PMID- 20669815
TI  - A comparative clinical study investigating the efficacy of a dentifrice
      containing 8% strontium acetate and 1040 ppm fluoride in a silica base and a
      control dentifrice containing 1450 ppm fluoride in a silica base to provide
      immediate relief of dentin hypersensitivity.
AB  - OBJECTIVE: The objective of this clinical study was to evaluate and compare the
      efficacy of a dentifrice containing 8% strontium acetate and 1040 ppm fluoride
      (from sodium fluoride) in a silica base (test dentifrice) to a control dentifrice
      containing 1450 ppm fluoride (from sodium fluoride) in a silica base, to reduce
      dentin hypersensitivity immediately after a single dab-on self-application, and
      after subsequent twice-daily brushing for three days. METHODS: This was a
      randomized, examiner-blind, two-arm parallel group, three-day clinical study with
      seventy-nine subjects, stratified based on baseline tooth sensitivity. Tooth
      sensitivity was determined through subject responses to both evaporative (Schiff
      and Visual Analogue Scale [VAS]) and tactile stimuli (Yeaple probe), prior to and
      immediately after subjects self-applied a single pea-sized amount of either the
      test or control dentifrice to qualifying sensitive teeth, massaging the
      toothpaste onto the sensitive area for one minute. Tooth sensitivity was further
      assessed in response to the same stimuli after subjects brushed twice daily for
      an additional three days. Subject assessments were performed by the same examiner
      throughout the study. RESULTS: Seventy-nine subjects completed this clinical
      study. Both subject groups exhibited reductions in dentin hypersensitivity
      directly after a single dab-on application. These reductions were significant
      across all measures for the test dentifrice. Between-treatment analyses showed
      the test dentifrice to be significantly better at relieving subjects' sensitivity
      across all measures (Schiff p = 0.0003, tactile p = 0.0003, and VAS p = 0.0077)
      compared to the control. After the additional three days of twice-daily brushing,
      between-treatment analyses showed the test dentifrice to be significantly better
      at relieving subjects' sensitivity across all measures (Schiff p = 0.0102,
      tactile p = 0.0493, and VAS p = 0.0067) than the control dentifrice. CONCLUSION:
      The 8% strontium acetate, 1040 ppm fluoride dentifrice provided significant
      within-treatment reductions in dentin hypersensitivity for all measures at both
      time points (immediate and three-day brushing). Compared to the control
      dentifrice, significant between-treatment reductions in sensitivity were observed
      after a single dab-on application for all measures, and following the additional
      twice-daily brushing for three days in favor of the 8% strontium acetate, 1040
      ppm fluoride dentifrice.

PMID- 20669816
TI  - A comparative clinical study investigating the efficacy of a test dentifrice
      containing 8% strontium acetate and 1040 ppm sodium fluoride versus a marketed
      control dentifrice containing 8% arginine, calcium carbonate, and 1450 ppm sodium
      monofluorophosphate in reducing dentinal hypersensitivity.
AB  - OBJECTIVE: The objective of this clinical study was to evaluate and compare the
      efficacy in reducing dentin hypersensitivity of an 8% strontium acetate, 1040 ppm
      sodium fluoride dentifrice to a marketed control 8% arginine, calcium carbonate,
      1450 ppm sodium monofluorophosphate dentifrice after twice-daily brushing for
      two, four, and eight weeks. METHODS: This was a randomized, examiner-blind, two
      arm parallel group, eight-week longitudinal clinical study with seventy-nine
      subjects, stratified based on baseline tooth sensitivity (Schiff score, Yeaple).
      Subjects brushed with either an 8% strontium acetate-based dentifrice or a
      marketed 8% arginine calcium carbonate dentifrice twice daily for approximately
      one minute. At screening, baseline, weeks two, four, and eight, subjects' tooth
      sensitivity was determined through both evaporative (Schiff and Visual Analogue
      Scale [VAS]) and tactile stimuli (Yeaple probe). Subject assessments using each
      stimulus were performed by the same examiner throughout the study. RESULTS:
      Seventy-seven subjects completed this clinical study. Both subject groups
      exhibited significant cumulative reductions from baseline to Days 14, 28, and 56
      in dentin hypersensitivity as measured by Schiff, Yeaple, and VAS (for the 8%
      strontium acetate group, p < or = 0.0001 for all time points; for the 8% arginine
      calcium carbonate group, p = 0.0031 for Yeaple at Day 14, p = 0.0015 for VAS at
      Day 14, and p < 0.0001 for all remaining measures and time points). No
      significant differences (p > 0.05) were observed between treatments for any of
      the time points and measures except for tactile sensitivity at Day 56, for which
      the 8% strontium acetate-based dentifrice was statistically superior (p = 0.0391)
      to the control 8% arginine calcium carbonate dentifrice. CONCLUSION: The 8%
      strontium acetate, 1040 ppm sodium fluoride dentifrice provided significant
      reductions in dentin hypersensitivity (p < 0.0001) after two, four, and eight
      weeks of product use. Comparisons to a control 8% arginine calcium carbonate
      dentifrice showed no significant differences (p > 0.05) apart from tactile
      (Yeaple) sensitivity at week 8, where the 8% strontium acetate-based dentifrice
      showed significant improvement over the control (p = 0.0391).

PMID- 20669817
TI  - Evidence for the efficacy of an 8% strontium acetate dentifrice for instant and
      lasting relief of dentin hypersensitivity.
AB  - An 8% strontium acetate, 1040 ppm sodium fluoride-based dentifrice has been
      demonstrated in in vitro and in situ studies to provide deep and acid-resistant
      tubule occlusion. Clinical efficacy studies have shown instant and lasting dentin
      hypersensitivity relief from this dentifrice, which has recently been launched by
      GlaxoSmithKline Consumer Healthcare as Sensodyne Rapid Relief.

PMID- 20669818
TI  - GMC guidance will help GPs improve end life care.

PMID- 20669819
TI  - State prevention of tuberculosis. 1910.

PMID- 20669820
TI  - Chest pain of recent onset requires prompt diagnosis.
AB  - The NICE guidance on recent onset chest pain urges GPs to assess the nature and
      timing of acute pain rapidly and arrange urgent admission for suspected acute
      coronary syndrome. A 12-lead ECG should be performed and treatment commenced with
      300 mg aspirin and GTN spray. Other pain relief such as opiates should be
      considered. However, starting management and recording a resting ECG should not
      delay transfer to hospital. Patients should be monitored while awaiting transfer.
      GPs can diagnose stable angina either on clinical assessment alone or combined
      with diagnostic testing (anatomical testing for obstructive coronary disease
      and/orfunctional testing for myocardial ischaemia). The presence or absence of
      the following three factors should be noted: a constricting discomfort in the
      front of the chest, or in the neck, shoulders, jaw, or arms; the discomfort is
      precipitated by physical exertion; the discomfort is relieved by rest or GTN
      within about 5 minutes. If all three factors are present the symptoms should be
      classified as typical angina, two factors atypical angina and one or none of
      these factors non-anginal chest pain. Once the initial assessment is complete the
      guidance recommends estimating the likelihood of coronary disease based on risk
      factors, age, sex and symptom classification. If clinical assessment suggests
      typical angina and the estimated likelihood of coronary disease is >90%, NICE
      advises that further diagnostic investigation is unnecessary. These patients
      should be managed as having angina. If the estimated likelihood of coronary
      disease is <10% then other non-ischaemic causes of chest pain should be
      considered.

PMID- 20669821
TI  - Managing unstable angina and non-ST elevation MI.
AB  - Acute coronary syndrome (ACS), encompassing unstable angina (UA), non-ST
      elevation myocardial infarction (NSTEMI) and ST elevation myocardial infarction
      (STEMI), is often the result of an acute thrombotic occlusion of the coronary
      vessels, associated with atheromatous plaque rupture or erosion. ACS is
      associated with a severely impaired prognosis and requires prompt and efficient
      specialist treatment. The clinical presentation may be identical across all three
      components of ACS. Establishing an accurate diagnosis without delay is of
      paramount importance to start treatment promptly. Patients with suspected ACS
      need to be referred immediately to A&E. Prehospital treatment, which includes
      aspirin, nitrates, morphine and oxygen (if hypoxic), should be initiated rapidly.
      Important features pointing towards a diagnosis of ACS include: typical
      characteristics of chest pain, presence of risk factors, and ECG changes
      suggestive of myocardial ischaemia. Chest discomfort in patients with ACS
      typically occurs at rest, is anginal in character and can range from mild
      tightness to central crushing chest pain. It may be associated with nausea,
      dyspnoea or diaphoresis. The chest pain may radiate to the arms, back or jaw and
      is often >20 minutes in duration. An accurate clinical history and a detailed
      examination are vital. Initial investigations are the same for all ACS events,
      with the need for urgent serial ECGs and the measurement of cardiac troponin
      levels, to assess myocardial damage. In NSTEMI, ECG changes suggestive of
      ischaemia are often present and associated with elevated cardiac troponin. In UA,
      there is a considerable reduction in myocardial perfusion leading to symptoms;
      but there is no rise in cardiac troponin. Risk stratification is imperative in
      assessment of ACS to allow efficient delivery of specialist care. Treatment
      includes: antiplatelets; antithrombotic agents; angina drugs; analgesia, and PCI.

PMID- 20669822
TI  - Tackling obesity in adult primary care.
AB  - Obesity is a growing problem. In England in 2008, 66% of men and 57% of women had
      a BMI >25 kg/m2; within this 24% of men and 25% of women were obese with a BMI
      >30 kg/m2. Obesity is a major contributing cause of disease. The relative risk
      (RR) of diabetes in overweight men is 2.40 and in obese men 6.74 compared with
      men with a BMI in the normal range. The respective RR values in women are 3.92
      and 12.41. There is a 40% increased risk of death from CVD for every 5 kg/m2
      increase in BMI above 25 kg/m2. Obesity is also associated with a raised risk of:
      fertility problems, cirrhosis, osteoarthritis, pregnancy complications,
      obstructive sleep apnoea and asthma. Patients should be offered advice on dietary
      change and increasing physical activity which includes behavioural components.
      Encouragement to make small changes in a sustained way can make significant
      differences to energy balance. Physical activity should be of moderate intensity
      (increased heart rate and breathing but still able to converse). Drug treatment
      is a useful addition when lifestyle measures alone are not effective. Evidence is
      increasing for the effectiveness of bariatric surgery in treating obesity-related
      disease, particularly diabetes.

PMID- 20669823
TI  - Sun-related conditions.

PMID- 20669824
TI  - Concerning the preservation of health in the tropics. 1910.

PMID- 20669826
TI  - The cost of making a mistake.

PMID- 20669827
TI  - CNST maternity standards and assessments and other NHSLA risk management
      initiatives.

PMID- 20669829
TI  - The fight for emancipation.

PMID- 20669828
TI  - Soapsuds: a lighter way of applying ethics to midwifery practice.

PMID- 20669830
TI  - Midwives and social networking.

PMID- 20669831
TI  - Can all-fours breech birth ever be a reality within the NHS?

PMID- 20669832
TI  - Profiling the professional doctorate.

PMID- 20669833
TI  - Help! MR SPARE: a new mnemonic for shoulder dystocia?

PMID- 20669834
TI  - Midwifery conferences: what's the point?

PMID- 20669835
TI  - Midwifery basics: understanding research (8). Critiquing research.

PMID- 20669836
TI  - Not such a different role.

PMID- 20669838
TI  - EHR versus EMR: what's in a name?

PMID- 20669837
TI  - The quiet of birth and breastfeeding.

PMID- 20669839
TI  - Solving the $31 billion uncompensated care problem.

PMID- 20669840
TI  - Great expectations--time for great preparations?

PMID- 20669841
TI  - Time for a change in your revenue cycle technology?
AB  - An assessment of the ROI of purchasing new revenue cycle technology should
      consider four questions: How well will a new revenue cycle system help your
      organization improve financial performance? Will the new system result in a lower
      cost to collect? How does the cost of the system compare with competitive
      systems? Would select system tweaks provide the same or as sufficient
      improvements as a system change would?

PMID- 20669842
TI  - Afresh look at capital investments.
AB  - Hospitals should focus on optimizing performance in five primary areas of capital
      investment: facilities, IT, physician networks, service lines, and clinical
      equipment/technology. Hospitals require a broad evaluation framework to help
      identify the key issues and concerns associated with each area. Discipline is
      critical to this process, so that every area receives its due consideration.

PMID- 20669843
TI  - Don't panic: how CFOs are facing the new economic reality.
AB  - CFOs at hospitals throughout the country are implementing strategic initiatives
      that can help their organizations succeed in challenging times: Revising
      strategic plans, Reassessing capital capacity, Leveraging IT to enhance revenue
      management.

PMID- 20669844
TI  - Breaking down IT silos: a "connected" way to improve customer experience and the
      bottom line.
AB  - Hospitals can provide customer service like Amazon.com without purchasing new
      technology. Making technology interactive requires sharing patient data across
      applications and enhancing existing IT with decision support. Breaking down
      technology silos between hospital and outpatient care provider systems
      significantly improves efficiency, lowers costs, and speeds care delivery.

PMID- 20669845
TI  - Keys to engaging clinicians in clinical IT.
AB  - Suggestions for gaining active participation of clinicians in the design and
      implementation of a clinical IT system include: Selecting open and easy-to-use
      systems, Gaining organization-wide buy in, Successfully articulating the benefits
      of these technologies for both patients and the organization.

PMID- 20669846
TI  - Financing to meet community needs: a guide for small hospitals.
AB  - To succeed in the current financial markets, small hospitals need flexible
      project and financing plans. Many small local banks today can offer small
      hospitals financing solutions on par with what was previously offered only by the
      country's strongest investment-grade rated banks. Federal assistance through
      programs such as HUD's Section 242 mortgage insurance program is also a viable
      option for small hospitals.

PMID- 20669847
TI  - What's next for revenue cycle technology?
AB  - When choosing a new revenue cycle management (RCM) solution, hospitals must
      decide whether to go with a best-of-breed solution or an enterprisewide or single
      vendor solution. A recent study suggests that most organizations are opting for
      the sole-source solution, because of the promise of enterprisewide integration.
      RCM products appear to be meeting purchasers' expectations, but many do not
      believe the products have yet achieved adequate functionality, and third-party
      bolt-on applications still seem necessary for some revenue cycle processes.

PMID- 20669848
TI  - Online payments in the new retail environment.
AB  - Virtual business offices are a key part of many hospitals' web strategies.
      Patients are ready and willing to pay their hospital bills online. Web-based
      payment centers can help cut self-pay days in A/R and increase collections.
      Proper marketing is essential to attract patients to a hospital's online business
      office.

PMID- 20669849
TI  - Targeted business intelligence pays off.
AB  - Application business intelligence can accomplish much of what large-scale,
      enterprisewide efforts can accomplish: Focus on a variety of data that are
      interrelated in a meaningful way, Support decision making at multiple levels
      within a given organization, Leverage data that are already captured but not
      fully used, Provide actionable information and support quick response via a
      dashboard or control panel.

PMID- 20669850
TI  - Implementing a patient estimating tool.

PMID- 20669851
TI  - Tough times call for data-driven decisions.

PMID- 20669852
TI  - 3 steps for improving 'red flag' compliance.

PMID- 20669853
TI  - What would you do? What competitive strategy makes sense?

PMID- 20669854
TI  - Early look at coding trends under MS-DRGs.

PMID- 20669855
TI  - Indicators of a new depression diagnosis in nursing home residents.
AB  - Depression affects approximately 30% to 40% of nursing home residents but
      frequently goes unrecognized. Using the Missouri Minimum Data Set, we aimed to
      determine whether changes in clinical status, other than mood changes, were
      associated with new depression diagnosis in residents 65 and older without a
      recorded depression diagnosis. Of 127,587 potential participants, 14,371 met
      inclusion criteria and were not depressed at baseline (Time 0). At the next
      quarterly assessment (Time 1), 1,342 (9.3%) had acquired a new diagnosis of
      depression. Residents with new depression were significantly younger and less
      cognitively impaired. Nearly 30% had a decline in activities of daily living
      (ADL) performance. The multivariate model predicting depression showed that
      increased verbal aggression, urinary incontinence, increased pain, weight loss,
      change in care needs, cognitive decline, and ADL decline significantly increased
      the likelihood of new depression diagnosis. The pattern of decline identified
      here may provide additional clues to the presence of underlying depression.

PMID- 20669856
TI  - Communication between nurses and unlicensed assistive personnel in nursing homes:
      explicit expectations.
AB  - Effective communication is at the core of quality improvement efforts. This study
      identified and explored the written guidelines for what, how, and when nurses and
      unlicensed assistive personnel (UAP) are expected to communicate regarding
      residents' status and care needs. Documents from six nursing homes were analyzed
      for this descriptive study, from which two primary themes emerged. First,
      extensive and explicit guidelines were identified for UAP-to-nurse communication,
      in comparison to few corresponding guidelines for nurses. Second, written
      guidelines for UAP communication were identified in multiple documents, with
      variations across sites in the situations requiring communication, the level of
      detail, and the format for how UAP-to-nurse communication should occur (i.e.,
      verbal, written). This study raises the issue of the extent to which explicit
      organizational structures and written guidelines support and reinforce nurses'
      scope of practice, the translation of UAP role expectations into actual practice,
      and the effectiveness of communication to promote quality care.

PMID- 20669857
TI  - A theory-based Self-Care Talk intervention for family caregiver-nurse
      partnerships.
AB  - Family caregivers need assistance with information, support, and advice from
      nurses and other health care professionals to successfully meet the demands of
      caregiving. Self-Care TALK (SCT) is a theory-based nursing intervention designed
      to improve the health and well-being of older adult spouse caregivers. The Self
      Care for Health Promotion in Aging Model (S-CHPA) provides a framework for
      development of SCT. Key to implementation of the SCT intervention is partnership
      building between nurses and caregivers, which is fostered through relational
      conversations. In this article, the model and intervention are described, and an
      individual example is provided to show the application of the model in practice.
      Implications for practice and research are explored.

PMID- 20669858
TI  - Caring for older adults with dementia when disaster strikes.
AB  - Diseaser emergencies are occurring with seemingly increased frequency. The
      likelihood that gerontological nurse will be involved in a disaster scenario,
      regardless of practices setting, is real. Instead of recoiling from this
      likelihood, the best approach is preparedness. In this article we examine what
      constitutes a disaster and how it differs from an emergency, as well as the
      potential impact of disaster on older adults in general and those with dementia
      in particular. Concepts of sheltering in plac, caring for older adults with
      dementia in a temporary shelter, and partnering with nurses in acute care
      settings are discussed.

PMID- 20669859
TI  - A question of delegation: unlicensed assistive personnel and the professional
      nurse.
AB  - As the American population of older adults increase and the nursing shortage
      widens, professional nurse caring for older adults are often confronted with
      managing an increased number of patients. To care for more patients safely and
      cost effectively, many health care facilities and organizations are creating
      positions for and utilizing a large number of unlicensed assistive personnel
      (UAP). Although unlicensed, these health care workers have become a fixture in
      health care facilities, especially those that care for older adults. To provide
      competent care for a larger population of patients, the professional nurse has
      had to become proficient in delegation. while delegating tasks to UAP may seem
      like a quick and easy determination, a great deal of accountability,
      responsibility, and liability is place on the health care facility and the
      individual nurses.

PMID- 20669861
TI  - Thai nursing students' knowledge and health beliefs about AIDS and use of
      universal precautions: a cross-sectional descriptive research study.
AB  - This study examined Thai nursing students' knowledge and health beliefs about the
      use of universal precautions to prevent infections, particularly HIV. After
      providing informed consent, 26 nursing students participated in the study. The
      students responded to a questionnaire with four sections: demographics,
      education, knowledge about universal precautions and transmission of HIV, and
      health belief. Students had substantial knowledge about the transmission of HIV;
      however they were not confident in the use of universal precautions to prevent
      transmission. This research will assist occupational health nurses in hospitals
      and educational institutions develop programs to enhance skills and attitudes to
      prevent HIV infection.

PMID- 20669862
TI  - Staff teamwork in long-term care facilities: the influence of management style,
      training, and feedback.
AB  - The purpose of this study was to describe the organizational factors associated
      with high and low amounts of teamwork among direct-care workers in long-term care
      (LTC) facilities. A systematic analysis of observation data collected at 20 LTC
      facilities was first used to categorize facilities as high-, moderate-, or low
      teamwork facilities. Next, qualitative analysis of 59 interviews collected in 4
      high-teamwork and 5 low-teamwork facilities was used to identify the
      organizational factors associated with high and low teamwork. Findings showed
      that high- and low-teamwork LTC facilities in this study differed in three
      organizational areas: management style, training, and feedback and recognition.
      As such, improved teamwork in LTC facilities may result from changes to basic
      management practices, such as training and employee feedback.

PMID- 20669863
TI  - Storytelling by community-dwelling older adults: perspectives of home care
      workers.
AB  - The purpose of this exploratory, qualitative study was to investigate
      storytelling by home care clients to their home care workers (HCWs). Specific
      research questions were: (a) When does storytelling by a care recipient occur
      during usual care?; (b) How do HCWs engage older clients in storytelling?; (c)
      How do HCWs respond to the stories told by clients?; and (d) What is the
      perceived effect of storytelling by older clients on the relationship between the
      client and the HCW? Two focus groups consisting of 10 HCWs each were conducted.
      Verbatim transcripts of both focus groups were analyzed using the constant
      comparative analysis method. Categories and concepts were identified.
      Characteristics of the HCW and client set the stage for storytelling. The process
      of storytelling included context, triggers, and temporal aspects. HCWs also
      shared the content of stories, the impact on their relationship with the client,
      and the perceived effect on each individual. A visual model depicting the nature
      of storytelling in association with the care of older clients is presented.

PMID- 20669864
TI  - Death in the nursing home: an examination of grief and well-being in nursing
      assistants.
AB  - The grief that nurses experience when patients and residents die can be complex
      and has been linked to both problematic (e.g., depression) and beneficial (e.g.,
      gains in coping) outcomes. In this study, 380 nursing assistants working in the
      nursing home setting were surveyed to gain an understanding of the relationship
      between grief and well-being. Findings indicated that participants experienced
      both distress and growth in their grief. Those who experienced greater distress
      from grief reported significantly higher levels of burnout and lower levels of
      psychological and physical well-being. Conversely, participants who experienced
      greater growth from their grief reported significantly lower levels of burnout,
      higher levels of psychological and physical well-being, and higher levels of job
      satisfaction. These findings suggest that grief may be an important determinant
      of well-being in nursing assistants, which, in turn, may impact quality of care
      in the nursing home.

PMID- 20669865
TI  - Potential adverse effects of discontinuing psychotropic drugs. Part 3:
      Antipsychotic, dopaminergic, and mood-stabilizing drugs.
AB  - Abrupt discontinuation of antipsychotic drugs in patients with schizophrenia is
      associated with earlier, and often more severe, illness episodes than are seen
      with gradual discontinuation. Antipsychotic drugs can cause various abnormal
      motor syndromes, but abruptly stopping them has been associated with the
      seemingly paradoxical development of similar motor syndromes, such as withdrawal
      dyskinesias, parkinsonian symptoms, dystonias, and neuroleptic malignant
      syndrome. Dopamine-releasing and dopamine-agonist drugs are used to treat some of
      the motor syndromes caused by antipsychotic drugs, but their abrupt
      discontinuation can also be associated with abnormal syndromes. When
      antipsychotic drugs, lithium, or certain anticonvulsant drugs are used for
      treatment of bipolar disorder, rapid versus gradual discontinuation is more
      likely to lead to greater mood instability and manic relapse. If necessary, these
      medications should be gradually tapered to minimize all types of adverse
      discontinuation effects. Patients should be educated about the possible adverse
      effects of abrupt medication discontinuation.

PMID- 20669866
TI  - Othello syndrome. Preventing a tragedy when treating patients with delusional
      disorders.
AB  - Othello syndrome, sometimes referred to as delusional, pathological, morbid, or
      erotic jealousy, is a rare delusional disorder with high-risk implications. This
      article provides an overview of Othello syndrome and includes an individual
      example as well as a review of the literature. Pharmacological interventions and
      dialectical behavior therapy are discussed as options for pathological jealousy.
      Nursing considerations and assessment strategies of delusional jealousy are
      described for identification and evaluation of risk factors. Patient safety is
      addressed, and collaborative interventions are proposed for treatment. Staff
      development for the treatment team is advocated to help staff identify delusional
      patients and act prudently to avert possible tragic consequences associated with
      Othello syndrome.

PMID- 20669867
TI  - Childhood adversities and adult health.
AB  - Child abuse and neglect have lifelong ramifications for adult mental health and
      health in general. In this brief overview, a range of childhood adversities
      (including prenatal substance exposure and prenatal malnutrition) is reviewed,
      and the evidence for their later negative implications is considered. The role of
      a chronically stressed hypothalamic-pituitary-adrenal axis likely has significant
      influence in this process. Strategies for nurses include developing awareness of
      the presence of early adversity in the lives of many Americans, as well as
      helping parents improve their functional status by treating mental illness and
      addictive disorders.

PMID- 20669868
TI  - Women's responses to unemployment of their spouse. Implications for psychiatric
      nurses.
AB  - The current economic recession has resulted in extremely high rates of
      unemployment, with the majority of those losing jobs being men. There is much
      research exploring how men respond to unemployment, but little examines how wives
      experience this crisis. Although nearly half of the workforce is now female, many
      women are co-providers, not sole providers. This article uses a historical
      perspective within a framework of role theory to help psychiatric nurse
      clinicians understand the possible responses of women who seek counseling after
      their spouses become unemployed. Counseling interventions are suggested, and an
      individual example is presented. Directions for future research are noted.

PMID- 20669869
TI  - Cranial electrotherapy stimulation for the treatment of depression.
AB  - More prevalent in women than men, clinical depression affects approximately 15
      million American adults in a given year. Psychopharmaceutical therapy accompanied
      by psychotherapy and wellness interventions (e.g., nutrition, exercise,
      counseling) is effective in 80% of diagnosed cases. A lesser known adjunctive
      therapy is that of cranial electrotherapy stimulation (CES). The major hypothesis
      for the use of CES in depression is that it may reset the brain to pre-stress
      homeostasis levels. It is conjectured that the pulsed electrical currents emitted
      by cranial electrical stimulators affect changes in the limbic system, the
      reticular activating system, and/or the hypothalamus that result in
      neurotransmitter secretion and downstream hormone production. While evidence is
      good for applied research, basic research about the mechanisms of action for CES
      remains in its infancy. A review of the literature provides an overview of
      current research findings and implications for clinical mental health practice.

PMID- 20669870
TI  - A mentor-protege program for new faculty, Part II: Stories of mentors.
AB  - Mentorship has been identified as an influential factor in retaining new nursing
      faculty. A mentor-protege program for novice faculty was implemented to promote
      development of the proteges in their role as nurse educators. A qualitative
      research study conducted to illuminate the meaning of experiences of mentors led
      to the emergence of four patterns: The Significance of the Mentor-Protege
      Relationship, Communication as Important Between Mentor and Protege, The Mentor
      Protege Program-Protege's Perspectives, and The Mentoring Role as Expert
      Educator. The data from the study support the significance of providing
      mentorship to novice or new nurse educators. The data suggest that mentors
      benefit from participation in a mentor-protege program as much as the proteges.
      Similar programs are needed in nursing if we are to mentor and encourage faculty
      to begin and remain in the role of educators to combat the future nurse educator
      shortage.

PMID- 20669871
TI  - Reflective journal prompts: a vehicle for stimulating emotional competence in
      nursing.
AB  - This article focuses on the development and pilot-testing of 10 reflective
      journal prompts designed to stimulate reflection on emotional intelligence
      competencies. Goleman's framework of emotional intelligence domains and 18
      competencies was used to guide development of the prompts and analysis of student
      (N = 16) responses. A review of the literature related to emotional intelligence
      competencies and nursing education and practice is presented, and assumptions
      derived from the literature and guiding the project are summarized. Journal
      prompts are presented, and examples of student responses illustrating reflection
      on competencies are provided. The findings suggest that these progressive journal
      prompts are useful tools for introducing and stimulating reflection on emotional
      intelligence competencies in nursing students. Recommendations for use in a
      variety of nursing courses are discussed.

PMID- 20669872
TI  - Nursing student perceptions of intraprofessional team education using high
      fidelity simulation.
AB  - High-fidelity simulation in health professional programs helps educators and
      students meet the challenges of increasingly complex clinical practice settings.
      Simulation has been used primarily to train nursing students either in
      interprofessional teams or within their respective nursing training levels.
      However, students' experiences of learning alongside others in different levels
      or years of the nursing program have not been explored. BSN students (N = 48)
      were placed in intraprofessional teams (i.e., one student from each nursing
      level) to manage acute pediatric and adult simulation scenarios. Students were
      instructed to manage the clinical scenario based on their level of clinical
      competence and education. Following debriefing, students responded to a
      satisfaction survey regarding their simulation experiences and their perceptions
      of learning within an intraprofessional nursing team. Project results suggest
      that intraprofessional educational experiences provide rich learning
      opportunities for both third-year and fourth-year nursing students. In addition,
      simulation provides a context within which to support intraprofessional nursing
      student education.

PMID- 20669873
TI  - Continuous curriculum review in a bachelor of nursing program: preventing
      curriculum drift and improving quality.
AB  - Higher education institutions have rigorous internal accreditation processes for
      new courses and typically require thorough course reviews every 5 years. Courses
      such as nursing must also be accredited by professional registration boards.
      However, in the years between initial accreditation and formal reaccreditation
      cycles, the risk of a widening gap between the accredited curriculum and the
      taught curriculum is real when there is no process to monitor the changes that
      individual unit assessors make to their subjects as they teach them. This
      curriculum drift may interfere with the intended development of graduate
      attributes and the taxonomic structure of assessment tasks across the course.
      This article describes the implementation of a formative continuous curriculum
      review process that prevents curriculum drift and enhances the quality of a
      bachelor of nursing curriculum.

PMID- 20669874
TI  - Characteristics of effective simulated clinical experience instructors:
      interviews with undergraduate nursing students.
AB  - Effective clinical nursing instructors are essential for maximizing nursing
      students' educational experience. Due to a shortage of clinical placement sites
      and advancements in technology, nursing students are increasingly learning
      clinical judgment and decision making in the simulated clinical experience (SCE)
      with human patient simulators. In this environment, SCE instructors help students
      acquire knowledge and skills in decision making in a controlled, risk-free,
      hospital-like clinical environment. Using informal student interviews, this study
      examined nursing student perceptions of the characteristics of an effective
      instructor in the simulated clinical experience. To capture information about the
      characteristics of effective SCE instructors, interviews were conducted with
      students (N = 8) from two universities in Northern California. All participants
      had experience working with human patient simulators in the simulation
      laboratory. Students identified six themes for SCE instructors: Personality,
      Teaching Ability, Evaluation, Nursing Competence, Interpersonal Relationships,
      and Realism. Further research on the similarities and differences of this new
      educational environment is recommended.

PMID- 20669875
TI  - Integrating psychosocial skills into a medical-surgical curriculum in a
      baccalaureate nursing program.
AB  - With the increasing acuity levels of hospitalized patients, faculty members
      struggle with accessing clinical sites for undergraduate students. Teaching
      students how to interact with patients and their families can often take second
      place to attending to the many needs and safety issues in caring for acutely ill
      individuals, particularly in medical-surgical settings. Over the past several
      years, the psychiatric and medical-surgical faculty members in the nursing
      department of a college in Boston have struggled with how best to prepare
      students for both the physical and psychosocial aspects of care. In this article,
      the evolution of our psychiatric consultation-liaison model is discussed.

PMID- 20669876
TI  - Frameworks for patient safety in the nursing curriculum.
AB  - Patient safety has recently received a great deal of media coverage. Professional
      and regulatory agencies have indicated that patient safety education should be
      provided to health care workers to improve health outcomes. This study's primary
      purpose was to gain a better understanding of the current status of patient
      safety awareness among prelicensure nursing students. Data were collected from
      two samples (N = 150 and 318), and nursing curricula were examined from seven
      institutions. Measurement integrity studies indicated that patient safety
      awareness can be measured validly and reliably. Demographic variables were
      correlated with patient safety awareness. A content analysis found that all of
      the participating nursing schools included at least three of the six core
      competencies of the Quality and Safety Education for Nurses (QSEN) (Cronenwett et
      al., 2007) in their curriculum; one school exhibited all six. Our findings led to
      conclusions and recommendations for nurse educators and for future research on
      patient safety education in the nursing curriculum.

PMID- 20669877
TI  - Predictability associated with exit examinations: a literature review.
AB  - The aims of this review are to study the accuracy of commercial examinations for
      predicting NCLEX-RN(r) success to determine whether there are significant
      differences in scores for graduates who pass the NCLEX-RN on their first attempt
      compared with those who do not and to discuss the implications of the findings in
      relation to progression policies. The most widely reported relationships between
      standardized test scores and NCLEX-RN success are associated with the Health
      Education Systems, Inc. (HESI) Exit Examination. In studies conducted over 4
      consecutive years with a total of 17,432 students, HESI was found to be 96.4% to
      98.3% accurate in predicting NCLEX-RN success for the highest scoring students.
      When HESI Exit Examination scores are used in logistic regression models, they
      are useful only in predicting NCLEX-RN success, not failure. These findings are
      consistent with reports regarding other computerized examinations. There is mixed
      evidence that these progression policies result in increased NCLEX-RN pass rates.

PMID- 20669878
TI  - Longitudinal study of optic cup progression in children.
AB  - PURPOSE: To determine the normative rate of cup-to-disc-ratio (C:D) progression
      in children and the effect of prematurity and low birth weight on this rate.
      METHOD: In a single pediatric ophthalmology practice, a single examiner evaluated
      optic cup size by serial ophthalmoscopy over a minimum of 5 years in 92 patients
      (184 eyes) without intraocular surgery or optic nerve disease. A cross-sectional
      analysis of C:D was performed per year of age from 0 to 10 years and linear
      regression was used to compare C:D progression between preterm and term children
      and between low versus normal birth weight children. RESULTS: Children exhibited
      progressive optic cupping. In term children, mean C:D increased by 0.0075 per
      year. Rate of mean C:D progression was double in children born preterm: 0.0160 (P
      = .049, comparison to term) per age-year. A similar, nonsignificant trend is
      observed when comparing low birth weight to normal children (P = .131).
      CONCLUSION: Prematurity and low birth weight are associated with increased rate
      of cupping in children. Clinicians should recognize that C:D progression is not a
      specific sign of glaucoma in children.

PMID- 20669879
TI  - Optical coherence tomography as an adjunctive tool for diagnosing papilledema in
      young patients.
AB  - PURPOSE: The authors examined the peripapillary (3.4-mm diameter) retinal nerve
      fiber layer thickness (RNFL thickness) as depicted by optical coherence
      tomography (OCT) in young patients with pseudopapilledema or papilledema.
      METHODS: In 17 consecutive patients (6 to 20 years old) with bilateral newly
      diagnosed papilledema or pseudopapilledema, the eye with the thicker mean global
      RNFL per patient was analyzed. Excluded were patients in whom cerebrospinal fluid
      opening pressure was between 190 and 250 mm H(2)O ("gray zone"). RNFL thickness
      was compared in eyes with papilledema and pseudopapilledema using the Mann
      Whitney U test. RESULTS: Papilledema was clinically diagnosed in 9 patients and
      pseudopapilledema in 6 patients; 2 patients were excluded. Median RNFL thickness
      in the eyes with papilledema was greater than that of both eyes with
      pseudopapilledema and controls at all 12 clock hours. In all 9 patients with
      papilledema, RNFL was thickened contiguously for 8 to 12 clock hours above the
      upper 95% confidence interval limit of normal. CONCLUSION: The peripapillary RNFL
      thickness as depicted by OCT was found to be a reliable adjunctive tool in the
      differentiation of newly diagnosed papilledema and pseudopapilledema in young
      patients. Larger cohorts are required to confirm these observations and
      conclusion.

PMID- 20669880
TI  - Clinical review of periorbital capillary hemangioma of infancy.
AB  - PURPOSE: To explore the role of intralesional steroid injections (ILSI) and oral
      steroids in the management of periocular hemangioma of infancy (HOI). METHODS: In
      this retrospective study, treatment options studied were observation, ILSI, and
      oral steroids. All children received adjunctive amblyopia treatment if required.
      The main indications for treatment were cosmetic, worsening astigmatism, and
      visual axis obscuration. Success was defined as complete HOI regression before
      the age of 5 years (cosmetic group), reduction of astigmatism of at least 1
      diopter cylinder (DC) (astigmatism group), or no evidence of amblyopia at the
      last follow-up (visual axis obscuration group). RESULTS: Twenty-four of 41
      children (58.5%) had amblyopia at presentation. Eighteen children formed the
      observation group, 17 children received ILSI, and 6 children received oral
      steroids. Successful outcome was achieved in all except 2 patients in the
      cosmetic group and 6 of 7 in the visual axis obscuration group. Mean astigmatic
      correction of all cases was 1.65 +/- 1.34 DC before treatment and 0.91 +/- 1.17
      DC after treatment, the change being statistically significant (P < .001).
      CONCLUSION: Observation appears to be a highly effective strategy if coupled with
      amblyopia therapy, especially for mild cases. Intralesional and oral steroids
      appear to be equally effective for lesions requiring treatment, but their exact
      role cannot be clearly determined in the presence of a spontaneously resolving
      lesion.

PMID- 20669881
TI  - Preferences of pediatric ophthalmologists and vitreoretinal surgeons of the
      treatment of scleral perforations during strabismus surgery.
AB  - PURPOSE: To evaluate the preferences of pediatric ophthalmologists and
      vitreoretinal surgeons with regard to the initial management of scleral
      perforation during strabismus surgery and to determine whether they perceived one
      mode of treatment conferred a significant advantage over another in terms of the
      complication rate. METHODS: Six hundred sixty-five pediatric ophthalmologists and
      494 vitreoretinal surgeons registered with their respective national
      organizations were invited by an e-mail to respond to an anonymous, web-based
      survey. The responses to the survey were compared between groups. RESULTS: A
      total of 169 ophthalmologists participated, 133 of whom were pediatric
      ophthalmologists and 36 vitreoretinal surgeons. Significantly more pediatric
      ophthalmologists than vitreoretinal surgeons recommend initially managing scleral
      perforation by observation (P = .001). Among pediatric ophthalmologists, method
      of treatment was not perceived to affect outcome (P = .75). However, laser
      photocoagulation was perceived to result in the best outcome among vitreoretinal
      surgeons (P = .03). CONCLUSION: Significant differences exist among pediatric
      ophthalmologist and vitreoretinal surgeon management preferences and perceived
      treatment outcomes for scleral perforation.

PMID- 20669882
TI  - Ocular parasitic diseases: a review on toxocariasis and diffuse unilateral
      subacute neuroretinitis.
AB  - Parasitic infections may damage various ocular tissues, thereby causing visual
      dysfunction. In 1950, Wilder described the first case in which larval forms of
      nematodal intestinal roundworms (Ascaridoidea: Ascaris, Toxocara, Ancylostoma,
      Necator, and Strongyloides) were implicated as a cause of intraocular disease.
      This review focuses on two disorders associated with parasitic infections: ocular
      toxocariasis and diffuse unilateral subacute neuroretinitis.

PMID- 20669883
TI  - Posterior chamber lens implantation with scleral fixation in children with
      traumatic cataract.
AB  - PURPOSE: To evaluate the outcomes of posterior chamber lens implantation with
      scleral fixation (SF-PCIOL) in children with traumatic cataract. METHODS: Twenty
      four eyes of 24 cases were included. All patients had corneal or corneoscleral
      lacerations that were primarily repaired. Traumatic cataract subsequently
      developed and SF-PCIOL was performed due to insufficient posterior capsule
      support. RESULTS: The average age of the patients was 5.8 years (range: 4 to 10
      years). All cases had SF-PCIOL implanted via internal route using triangular
      double scleral flaps made of 9-0 polypropylene after a complete anterior
      vitrectomy. Average follow-up was 14.6 +/- 4.3 months (range: 11 to 18 months).
      Visual acuity was increased at the last visit in 23 (96%) patients. Common
      postoperative complications were fibrinous reaction in 6 (25%) patients,
      transient intraocular pressure increase in 4 (17%) patients, membrane formation
      requiring removal in 1 (4%) patient, transient intraocular hemorrhage as vitreous
      hemorrhage in 1 (4%) patient, and retinal detachment in 1 (4%) patient after the
      postoperative second month. CONCLUSION: SF-PCIOL is an effective and reliable
      method in patients with pediatric traumatic cataract who had insufficient
      posterior capsule support.

PMID- 20669884
TI  - Making a practice an academic office.

PMID- 20669885
TI  - This issue: enhancing your pediatric practice.

PMID- 20669886
TI  - A 1-day-old boy with a liver mass.

PMID- 20669887
TI  - A 22-month-old boy with eye swelling.

PMID- 20669888
TI  - Opportunities for enhancing your pediatric practice through academic involvement.

PMID- 20669889
TI  - Enhancing your pediatric practice by incorporating undergraduate medical
      education.

PMID- 20669890
TI  - PROS: a research network to enhance practice and improve child health.

PMID- 20669891
TI  - Pediatric coding: what you need to know to enhance your clinical practice's
      reimbursement process.

PMID- 20669892
TI  - The medical home - as new as it is old.

PMID- 20669893
TI  - Stoichiometry and topology of the complex of the endogenous ATP synthase
      inhibitor protein IF(1) with calmodulin.
AB  - IF(1), the natural inhibitor protein of F(O)F(1)ATP synthase able to regulate the
      ATP hydrolytic activity of both mitochondrial and cell surface enzyme, exists in
      two oligomeric states depending on pH: an inactive, highly helical, tetrameric
      form above pH 6.7 and an active, inhibitory, dimeric form below pH 6.7 [ Cabezon
      , E. , Butler , P. J. , Runswick , M. J. , and Walker , J. E. ( 2000 ) J. Biol.
      Chem. 275 , 25460 -25464 ]. IF(1) is known to interact in vitro with the
      archetypal EF-hand calcium sensor calmodulin (CaM), as well to colocalize with
      CaM on the plasma membrane of cultured cells. Low resolution structural data were
      herein obtained in order to get insights into the molecular interaction between
      IF(1) and CaM. A combined structural proteomic strategy was used which integrates
      limited proteolysis and chemical cross-linking with mass spectrometric analysis.
      Specifically, chemical cross-linking data clearly indicate that the C-terminal
      lobe of CaM molecule contacts IF(1) within the inhibitory, flexible N-terminal
      region that is not involved in the dimeric interface in IF(1). Nevertheless,
      native mass spectrometry analysis demonstrated that in the micromolar range the
      stoichiometry of the IF(1)-CaM complex is 1:1, thereby indicating that binding to
      CaM promotes IF(1) dimer dissociation without directly interfering with the
      intersubunit contacts of the IF(1) dimer. The relevance of the finding that only
      the C-terminal lobe of CaM is involved in the interaction is two fold: (i) the
      IF(1)-CaM complex can be included in the category of noncanonical structures of
      CaM complexes; (ii) it can be inferred that the N-terminal region of CaM might
      have the opportunity to bind to a second target.

PMID- 20669894
TI  - Robust and photocontrollable DNA capsules using azobenzenes.
AB  - Various three-dimensional structures have been created on a nanometer scale using
      the self-assembly of DNA molecules. However, ordinary DNA structures breakdown
      readily because of their flexibility. In addition, it is difficult to control
      them by inputs from environments. Here, we construct robust and photocontrollable
      DNA capsules using azobenzenes. This provides a method to construct DNA
      structures that can survive higher temperatures and can be controlled with
      ultraviolet irradiation.

PMID- 20669895
TI  - Autonomous microfluidic control by chemically actuated micropumps and its
      application to chemical analyses.
AB  - Autonomous control of microfluidic transport was realized through the use of
      chemically actuated diaphragm micropumps connected to a network of controlling
      flow channels. A hydrogen peroxide (H(2)O(2)) solution was transported in the
      controlling flow channel by capillary action. Upon the solution's arrival at the
      lower compartment of a micropump filled with manganese dioxide (MnO(2)) powder, a
      volume change that accompanied the production of oxygen caused by the catalytic
      decomposition of H(2)O(2) induced inflation of the diaphragm. This in turn caused
      the movement of a solution in another network of flow channels formed in the
      upper layer. Micropumps that only exert pressure were also fabricated. By
      positioning the micropumps at appropriate locations in conjunction with
      additional flow-delaying components, the ejection of solutions from the reservoir
      of each micropump could be initiated at coordinated times. Furthermore, the
      solutions could be transported by the application of pressure from other
      micropumps. In other words, the information for switching from one micropump to
      another could be described on the chip in the form of a network of flow channels.
      This autonomous processing of solutions was demonstrated for enzymatic analyses
      of H(2)O(2), glucose, and lactate.

PMID- 20669896
TI  - Direct aerobic photo-oxidative synthesis of aromatic methyl esters from methyl
      aromatics via dimethyl acetals.
AB  - A useful method for facile synthesis of aromatic methyl esters from methyl
      aromatics via dimethyl acetals by aerobic photo-oxidation using inexpensive and
      easily handled CBr(4) as catalyst is reported. This is the first example for
      direct preparation of the corresponding aromatic methyl esters from methyl
      aromatics.

PMID- 20669897
TI  - Sorting single-walled carbon nanotubes by electronic type using nonionic,
      biocompatible block copolymers.
AB  - As-synthesized single-walled carbon nanotubes (SWNTs) typically possess a range
      of diameters and electronic properties. This polydispersity has hindered the
      development of many SWNT-based technologies and encouraged the development of
      postsynthetic methods for sorting SWNTs by their physical and electronic
      structure. Herein, we demonstrate that nonionic, biocompatible block copolymers
      can be used to isolate semiconducting and metallic SWNTs using density gradient
      ultracentrifugation. Separations conducted with different Pluronic block
      copolymers reveal that Pluronics with shorter hydrophobic chain lengths lead to
      higher purity semiconducting SWNTs, resulting in semiconducting purity levels in
      excess of 99% obtained for Pluronic F68. In contrast, X-shaped Tetronic block
      copolymers display an affinity for metallic SWNTs, yielding metallic purity
      levels of 74% for Tetronic 1107. These results suggest that high fidelity and
      high yield density gradient separations can be achieved using nonionic block
      copolymers with rationally designed homopolymer segments, thus generating
      biocompatible monodisperse SWNTs for a range of applications.

PMID- 20669898
TI  - Graphene oxide--polyelectrolyte nanomembranes.
AB  - Owing to its remarkable electrical, thermal, and mechanical properties, graphene,
      an atomic layer of carbon, is considered to be an excellent two-dimensional
      filler for polymer nanocomposites with outstanding mechanical strength along with
      the potential for excellent electrical and thermal properties. One of the
      critical limitations with conventional fillers is that the loading fraction
      required for achieving significant improvement in mechanical properties is
      relatively high, frequently reaching 50% for maximum strength. Here, we
      demonstrate that the mechanical properties of ultrathin laminated nanocomposites
      can be significantly enhanced by the incorporation of small amounts of a dense
      monolayer of planar graphene oxide (GO) flakes. Negatively charged functionalized
      graphene oxide layers were incorporated into polyelectrolyte multilayers (PEMs)
      fabricated in a layer-by-layer (LbL) assembly via Langmuir-Blodgett (LB)
      deposition. These LbL-LB graphene oxide nanocomposite films were released as
      robust freely standing membranes with large lateral dimensions (centimeters) and
      a thickness of around 50 nm. Micromechanical measurements showed enhancement of
      the elastic modulus by an order of magnitude, from 1.5 GPa for pure LbL membranes
      to about 20 GPa for only 8.0 vol % graphene oxide encapsulated LbL membranes.
      These tough nanocomposite PEMs can be freely suspended over large (few
      millimeters) apertures and sustain large mechanical deformations.

PMID- 20669899
TI  - Controllable self-assembly of PbS nanostars into ordered structures: close-packed
      arrays and patterned arrays.
AB  - Controllable self-assembly of uniform star-shaped PbS nanocrystals with six
      symmetric 100-oriented horns into highly ordered structures including close
      packed arrays and patterned arrays was realized by evaporation-induced assembly
      routes. First, large-area three-dimensional (3D) and two-dimensional (2D)
      hexagonal close-packed (hcp) arrays of PbS nanostars were assembled on clean Si
      substrate by drop coating and vertical deposition, respectively. Then, by using
      monolayer colloidal crystals (MCC) and inverted MCC (IMCC) as the template, a
      variety of non-close-packed (ncp) arrays of PbS nanostars with controllable
      patterns were fabricated through the vertical deposition method. With the MCC
      template, an ncp array of [111]-oriented PbS nanostars with three horns stably
      standing on the template plane was prepared, leading to the formation of novel
      star-sphere binary colloidal crystals with a stoichiometric star/sphere ratio of
      1. The reflectance spectrum of the resultant MCC-PbS composite array was
      measured, which exhibited a considerable red shift in the reflectance peak
      compared with the original MCC template. Alternatively, with the IMCC template,
      an ncp array of [001]-oriented PbS nanostars with a single horn stretched
      vertically upward was obtained. Furthermore, some novel patterns for PbS ncp
      arrays were readily fabricated using MCC/IMCC templates with larger periodic
      spacings. For the template-assisted assembly of PbS nanostars, the obtained PbS
      ncp arrays generally inherited the long-range hexagonal order from the initial
      MCC template. This assembly strategy is a versatile approach and may open a new
      route for the controlled assembly of anisotropic nanostructured materials into
      large-scale ordered arrays with desirable patterns.

PMID- 20669900
TI  - Interaction and localization of the retinitis pigmentosa protein RP2 and NSF in
      retinal photoreceptor cells.
AB  - RP2 is a ubiquitously expressed protein encoded by a gene associated with X
      linked retinitis pigmentosa (XLRP), a retinal degenerative disease that causes
      severe vision loss. Previous in vitro studies have shown that RP2 binds to ADP
      ribosylation factor-like 3 (Arl3) and activates its intrinsic GTPase activity,
      but the function of RP2 in the retina, and in particular photoreceptor cells,
      remains unclear. To begin to define the role of RP2 in the retina and XLRP, we
      have conducted biochemical studies to identify proteins in retinal cell extracts
      that interact with RP2. Here, we show that RP2 interacts with N-ethylmaleimide
      sensitive factor (NSF) in retinal cells as well as cultured embryonic kidney
      (HEK293) cells by mass spectrometry-based proteomics and biochemical analysis.
      This interaction is mediated by the N-terminal domain of NSF. The E138G and
      DeltaI137 mutations of RP2 known to cause XLRP abolished the interaction of RP2
      with the N-terminal domain of NSF. Immunofluorescence labeling studies further
      showed that RP2 colocalized with NSF in photoreceptors and other cells of the
      retina. Intense punctate staining of RP2 was observed close to the junction
      between the inner and outer segments beneath the connecting cilium, as well as
      within the synaptic region of rod and cone photoreceptors. Our studies indicate
      that RP2, in addition to serving as a regulator of Arl3, interacts with NSF, and
      this complex may play an important role in membrane protein trafficking in
      photoreceptors and other cells of the retina.

PMID- 20669902
TI  - The role of polymer in improving floc strength for filtration.
AB  - Dosing polymer to improve floc characteristics is a widely practiced method in
      water treatment to improve floc strength, and there is strong operational
      evidence showing the benefit of polymer dosing. However, there is a paucity of
      information on how polymer operates in terms of quantifying the resulting floc
      size and strength over different size scales. A dual particle sizing approach was
      used to monitor large floc that contain most of the sludge volume and small floc
      that can cause downstream treatability problems for systems with and without
      polymer dosing. The polymer investigated was a slightly anionic polyacrylamide
      dosed in water collected post dissolved air flotation at concentrations of 0-0.03
      mg L(-1). With increasing polymer dose, median floc size increased from 228 to
      325 microm. Floc responses to increased shear rate showed that polymer dosing
      increased resistance to floc break-up. While all of the flocs showed high
      potential to regrow, regrowth was greatest in polymer-dosed systems, where flocs
      exceeded the size that they had reached previously. Increasing the dose of
      polymer showed increased removal of small particles (<8 microm) showing that
      polymer was able to effectively remove particles that are liable to cause
      downstream problems.

PMID- 20669901
TI  - Infrared and EPR spectroscopic characterization of a Ni(I) species formed by
      photolysis of a catalytically competent Ni(I)-CO intermediate in the acetyl-CoA
      synthase reaction.
AB  - Acetyl-CoA synthase (ACS) catalyzes the synthesis of acetyl-CoA from CO, coenzyme
      A (CoA), and a methyl group from the CH(3)-Co(3+) site in the corrinoid iron
      sulfur protein (CFeSP). These are the key steps in the Wood-Ljungdahl pathway of
      anaerobic CO and CO(2) fixation. The active site of ACS is the A-cluster, which
      is an unusual nickel-iron-sulfur cluster. There is significant evidence for the
      catalytic intermediacy of a CO-bound paramagnetic Ni species, with an electronic
      configuration of [Fe(4)S(4)](2+)-(Ni(p)(+)-CO)-(Ni(d)(2+)), where Ni(p) and Ni(d)
      represent the Ni centers in the A-cluster that are proximal and distal to the
      [Fe(4)S(4)](2+) cluster, respectively. This well-characterized Ni(p)(+)-CO
      intermediate is often called the NiFeC species. Photolysis of the Ni(p)(+)-CO
      state generates a novel Ni(p)(+) species (A(red)*) with a rhombic electron
      paramagnetic resonance spectrum (g values of 2.56, 2.10, and 2.01) and an
      extremely low (1 kJ/mol) barrier for recombination with CO. We suggest that the
      photolytically generated A(red)* species is (or is similar to) the Ni(p)(+)
      species that binds CO (to form the Ni(p)(+)-CO species) and the methyl group (to
      form Ni(p)-CH(3)) in the ACS catalytic mechanism. The results provide support for
      a binding site (an "alcove") for CO near Ni(p), indicated by X-ray
      crystallographic studies of the Xe-incubated enzyme. We propose that, during
      catalysis, a resting Ni(p)(2+) state predominates over the active Ni(p)(+)
      species (A(red)*) that is trapped by the coupling of a one-electron transfer step
      to the binding of CO, which pulls the equilibrium toward Ni(p)(+)-CO formation.

PMID- 20669903
TI  - Rhenium-catalyzed didehydroxylation of vicinal diols to alkenes using a simple
      alcohol as a reducing agent.
AB  - A new method for the catalytic didehydroxylation of vicinal diols is described.
      Employing a readily available low-valent rhenium carbonyl complex and a simple
      alcohol as a reducing agent, both terminal and internal vicinal diols are
      deoxygenated to olefins in good yield. The optional addition of acid (TsOH,
      H(2)SO(4)) provides access to lower reaction temperatures. This new system
      enables the transformation of a four-carbon sugar polyol into an oxygen-reduced
      compound, providing promising evidence for its practical application to produce
      unsaturated compounds from biomass-derived materials.

PMID- 20669904
TI  - Catechol and humic acid sorption onto a range of laboratory-produced black
      carbons (biochars).
AB  - Although the major influence of black carbon (BC) on soil and sediment organic
      contaminant sorption is widely accepted, an understanding of the mechanisms and
      natural variation in pyrogenic carbon interaction with natural organic matter
      (NOM) is lacking. The sorption of a phenolic NOM monomer (catechol) and humic
      acids (HA) onto BC was examined using biochars made from oak, pine, and grass at
      250, 400, and 650 degrees C. Catechol sorption equilibrium occurred after 14 d
      and was described by a diffusion kinetic model, while HA required only 1 d and
      followed pseudo-second-order kinetics. Catechol sorption capacity increased with
      increasing biochar combustion temperature, from pine < oak < grass and from
      coarse < fine particle size. At lower catechol concentrations, sorption affinity
      (Freundlich constant, K(f)) was directly related to micropore surface area
      (measured via CO(2) sorptometry) indicating the predominance of specific
      adsorption. In contrast, HA exhibited an order of magnitude less sorption (0.1%
      versus 1%, by weight) due to its exclusion from micropores. Greater sorption of
      both catechol and HA occurred on biochars with nanopores, i.e. biochars made at
      higher temperatures. These findings suggest that addition of BC to soil, via
      natural fires or biochar amendments, will sequester abundant native OM through
      sorption.

PMID- 20669905
TI  - Hierarchic self-assembly of nanoporous chiral networks with conformationally
      flexible porphyrins.
AB  - We report the hierarchic design of homochiral 2D nanoporous networks under
      ultrahigh vacuum conditions on the Ag(111) surface by using a flexible porphyrin
      derivative as a primary unit. The conformational adaptation of the molecular
      module gives rise to two enantiomers upon 2D confinement, which self-assemble in
      enantiopure clusters made of three molecules reflecting chiral recognition, which
      constitute the secondary supramolecular building block mediating the formation of
      the tertiary complex open networks. Our results show that the creation of
      homochiral superstructures based on the hierarchical assembly of conformationally
      flexible molecular components constitutes a unique pathway toward the design of
      novel and functional chiral structures.

PMID- 20669906
TI  - Study of the amorphous glibenclamide drug: analysis of the molecular dynamics of
      quenched and cryomilled material.
AB  - Glibenclamide (GCM) is an oral hypoglycemic agent of the sulfonylurea group used
      in the treatment of non-insulin-dependent diabetes. Crystalline GCM is
      characterized by low bioavailability, which is attributed to its poor dissolution
      properties. It prompted us to prepare this drug in its amorphous form as a means
      to enhance its dissolution characteristics. Two different methods were used to
      convert crystalline GCM into the glassy form: quench-cooling of the melt and
      cryogenic milling. To monitor solid-state properties of the amorphous samples, X
      ray powder diffraction (XRD), infrared spectroscopy (FT-IR), differential
      scanning calorimetry (DSC), ultraperformance liquid chromatography (UPLC) and
      spectroscopy, and broadband dielectric spectroscopy (BDS) were applied. The
      results of UPLC separations along with associated infrared and NMR measurements
      unambiguously showed that the thermal degradation of the quenched GCM, as
      suggested in literature reports, does not occur. A similar analysis performed on
      the cryomilled material also did not indicate any chemical decomposition. On the
      other hand, both methods confirmed that the conversion to the amorphous form is
      connected with the amide-imidic acid tautomerism of the examined drug. Moreover
      it was shown that this transformation occurs regardless of the manner of
      amorphization. Finally, dielectric spectroscopy was employed to study the
      molecular dynamics of vitrified GCM. The analysis of the epsilon''(f) in terms of
      the KWW function from the dielectric measurements revealed the existence of an
      "excess wing" attributed to the true Johari-Goldstein process based on Ngai's
      coupling model. The dielectric properties of GCM obtained in the amorphous form
      both by rapid cooling of the melt and the cryogenic grinding of crystalline
      sample were also compared.

PMID- 20669907
TI  - Identification of metallothionein subisoforms in HPLC using accurate mass and
      online sequencing by electrospray hybrid linear ion trap-orbital ion trap mass
      spectrometry.
AB  - A comprehensive approach to the characterization of metallothionein (MT) isoforms
      based on microbore HPLC with multimodal detection was developed. MTs were
      separated as Cd(7) complexes, detected by ICP MS and tentatively identified by
      molecular mass measured with 1-2 ppm accuracy using Orbital ion trap mass
      spectrometry. The identification was validated by accurate mass of the
      corresponding apo-MTs after postcolumn acidification and by their sequences
      acquired online by higher-energy collision dissociation MS/MS. The detection
      limits down to 10 fmol and 45 fmol could be obtained by ESI MS for apo- and Cd(7)
      isoforms, respectively, and were lower than those obtained by ICP MS (100 fmol).
      The individual MT isoforms could be sequenced at levels as low as 200 fmol with
      the sequence coverage exceeding 90%. The approach was successfully applied to the
      identification of MT isoforms induced in a pig kidney cell line (LLC-PK(1))
      exposed to CdS nanoparticles.

PMID- 20669908
TI  - Multiwalled carbon nanotube (MWCNT) reinforced cellulose fibers by
      electrospinning.
AB  - Multiwalled carbon nanotubes (MWCNTs) were successfully incorporated in ultrafine
      cellulose fibers by electrospinning MWCNT-loaded cellulose acetate (CA)
      solutions, followed by deacetylation of CA to cellulose (cell). The mean fiber
      diameter reduced from 321 nm of the as-spun fibers to 257 and 228 nm of those
      with 0.11 and 0.55 wt % MWCNTs, respectively, and became more uniform. Hydrolysis
      of CA to cell further reduced the mean fiber sizes by another 8-16%. The MWCNTs
      were observed to be well-aligned along the fiber axes. The MWCNT/cell composite
      fibers had increased specific surface, from 4.27 m(2)/g to 5.07 and 7.69 m(2)/g
      at 0.11 and 0.55 wt % MWCNTs, respectively, and much improved water wettability.
      The mechanical properties of the fibers were also greatly enhanced with increased
      MWCNT loading levels. The fact that MWCNTs were observed in only about a third of
      the fibers at a very low 0.55 wt % loading suggests significantly higher tensile
      strength may be achieved by a further increase in MWCNT loadings.

PMID- 20669909
TI  - Tailoring lipoplex composition to the lipid composition of plasma membrane: a
      Trojan horse for cell entry?
AB  - The first interaction between lipoplexes and cells is charge-mediated and not
      specific. Endocytosis is considered to be the main pathway for lipoplex entry.
      Upon interaction between lipoplexes and the plasma membrane, intermixing between
      lipoplex and membrane lipids is necessary for efficient endocytosis. Here we
      study the mechanism of the different endocytic pathways in lipid-mediated gene
      delivery. We show that DC-Chol-DOPE/DNA lipoplexes preferentially use a raft
      mediated endocytosis, while DOTAP-DOPC/DNA systems are mainly internalized by not
      specific fluid phase macropinocitosys. On the other hand, most efficient
      multicomponent lipoplexes, incorporating different lipid species in their lipid
      bilayer, can use multiple endocytic pathways to enter cells. Our data demonstrate
      that efficiency of endocytosis is regulated by shape coupling between lipoplex
      and membrane lipids. We suggest that such a shape-dependent coupling regulates
      efficient formation of endocytic vesicles thus determining the success of
      internalization. Our results suggest that tailoring the lipoplex lipid
      composition to the patchwork-like plasma membrane profile could be a successful
      machinery of coordinating the endocytic pathway activities and the subsequent
      intracellular processing.

PMID- 20669910
TI  - Mechanism of photolytic decomposition of N-halamine antimicrobial siloxane
      coatings.
AB  - Generally, antimicrobial N-halamine siloxane coatings can be rehalogenated
      repetitively upon loss of their biocidal efficacies, a marked advantage over
      coatings containing other antimicrobial materials. However, the N-halamine
      materials tend to slowly decompose upon exposure to ultraviolet irradiation as in
      direct sunlight. In this work the mechanism of photolytic decomposition for the N
      halamine siloxanes has been studied using spectroscopic and theoretical methods.
      It was found that the N-chlorinated coatings slowly decomposed upon UVA
      irradiation, whereas the unhalogenated coatings did not. Model compound evidence
      in this work suggests that upon UVA irradiation, the N-Cl bond dissociates
      homolytically, followed by a Cl radical migration to the alkyl side chain
      connected to the siloxane tethering group. An alpha and/or beta scission then
      occurs causing partial loss of the biocidal moiety from the surface of the coated
      material, thus precluding complete rechlorination. NMR, FTIR, GCMS, and
      computations at the DFT (U)B3LYP/6-311++G(2d,p) level of theory have been
      employed in reaching this conclusion.

PMID- 20669911
TI  - Investigation of the formation process of photodeposited Rh nanoparticles on TiO2
      by in situ time-resolved energy-dispersive XAFS analysis.
AB  - The photodeposition process of Rh metal nanoparticles on a TiO(2) photocatalyst
      from RhCl(3) aqueous solution in the presence of methanol as a sacrificial
      oxidant, which consists of the direct reduction of Rh(3+) ions to Rh metal and
      the formation of Rh nanoparticles, was uncovered by in situ time-resolved energy
      dispersive X-ray absorption fine structure (DXAFS) analysis in a liquid-solid
      suspension state. The fractions of Rh metal particles and Rh(3+) precursor were
      estimated by the least-squares fitting of each X-ray absorption near-edge
      structure (XANES) spectrum by a linear combination of authentic spectra
      corresponding to Rh(0) and Rh(3+). The fraction of Rh metal linearly increased
      with photoirradiation time and saturated after 90 min of photoirradiation. The
      coordination number (Rh-Rh pair) was evaluated by the curve fitting of the Rh-Rh
      scattering at 2.45 A in the Fourier transforms (FT) of extended XAFS (EXAFS)
      spectra. The coordination number linearly increased with photoirradiation time
      and attained a constant value of 10 after 90 min of photoirradiation. This value
      is lower than that for the Rh foil (12). These suggest the formation of fine Rh
      metal nanoparticles on TiO(2). In addition, the diminution rate of Rh(3+) as
      determined by ICP analysis was in good agreement with the increased rates for the
      fraction of Rh metal particles estimated by XANES spectra and the coordination
      number (Rh-Rh pair) evaluated by FT-EXAFS spectra. This result strongly supports
      the fact that electrons generated by charge separation reduce the Rh(3+)
      precursor to an Rh metal particle at a moment in time and at a constant rate. The
      Rh particles do not grow in incremental steps, but Rh particles with a uniform
      size appear one after another on the surface.

PMID- 20669912
TI  - Effect of surface chemistry on the stability of gold nanostructures.
AB  - Understanding the role of surface chemistry in the stability of nanostructured
      noble-metal materials is important for many technological applications but
      experimentally difficult to access and thus little understood. To develop a
      fundamental understanding of the effect of surface chemistry on both the
      formation and stabilization of self-organized gold nanostructures, we performed a
      series of controlled-environment annealing experiments on nanoporous gold (np-Au)
      and ion-bombarded Au(111) single-crystal surfaces. The annealing experiments on
      np-Au in ambient ozone were carried out to study the effect of adsorbed oxygen
      under dynamic conditions, whereas the ion-bombarded Au single-crystal surfaces
      were used as a model system to obtain atomic-scale information. Our results show
      that adsorbed oxygen stabilizes nanoscale gold structures at low temperatures
      whereas oxygen-induced mobilization of Au surface atoms seems to accelerate the
      coarsening under dynamic equilibrium conditions at higher temperatures.

PMID- 20669913
TI  - Structural characterization of a mixed Langmuir-Blodgett film of a merocyanine
      dye derivative-deuterated arachidic acid binary system and the influence of
      successive hydrothermal treatment in the liquid phase on the film as investigated
      by polarized UV-visible and IR absorption spectroscopy.
AB  - We have investigated the structure of the mixed Langmuir-Blodgett (LB) film of a
      merocyanine dye derivative (MO(18))-deuterated arachidic acid (C(20)-d) binary
      system and the influence of successive hydrothermal treatment in the liquid phase
      (HTTL) on the mixed LB film by means of polarized UV-visible and IR absorption
      spectroscopy. The visible absorption band with in-plane anisotropy at 503 nm
      before HTTL transforms into an absorption band with in-plane isotropy at 557 nm
      after HTTL for 16-18 min through a peak maximum near 520 nm after HTTL for 2-12
      min. The degree of total MO(18) intramolecular charge transfer for the 503 nm
      band is the largest among those for all of the bands. Therefore, the 503 nm band
      is ascribed to the MO(18) H-like aggregation, based on its shape, peak height,
      and in-plane anisotropy, the subsequent change to two kinds of visible peaks by
      successive HTTL, and the most degree of MO(18) intramolecular charge transfer
      among all of the aggregation states. While the MO(18) hydrocarbon chain takes the
      all-trans conformation before HTTL, its conformation and orientation are most
      disarranged after HTTL for 2 min. Subsequently, the original conformation and
      orientation are recovered by degrees with successive HTTL, except after final
      HTTL for 18 min, when the orientation is again changed. On the other hand, the
      C(20)-d hydrocarbon chain maintains the all-trans conformation before and after
      HTTL. The orientation of the C(20)-d hydrocarbon chain after HTTL for 2 min is
      more ordered than that before HTTL, with the nature of the C(20)-d subcell
      packing changing from hexagonal to orthorhombic. During successive HTTL from 2 to
      18 min, the C(20)-d orientation is gradually disorganized but with the
      orthorhombic nature remaining constant. Thus, the variations in the conformation
      and orientation of the MS(18) hydrocarbon chain and in the orientation of the
      C(20)-d hydrocarbon chain tend to change from ordered and disordered structures
      and turn to more disordered and ordered ones, respectively, where the former is
      mainly caused by the priority action of thermal energy and the latter by
      hydrophobic effect due to the presence of warm water. Consequently, it is
      suggested that there is a correlation between the degree of structural order for
      both hydrocarbon chains and the preferential action that takes place during HTTL.

PMID- 20669914
TI  - Ionization and structural changes of the DMPG vesicle along its anomalous gel
      fluid phase transition: a study with different lipid concentrations.
AB  - Dispersions of saturated anionic phospholipid dimyristoyl phosphatidylglycerol
      (DMPG) have been extensively studied regarding their peculiar thermostructural
      behavior. At low ionic strength, the gel-fluid transition is spread along nearly
      17 degrees C, displaying several thermal events in the calorimetric profile that
      is quite different from the single sharp peak around 23 degrees C found for
      higher ionic strength DMPG dispersions. To investigate the role of charge in the
      bilayer transition, we carefully examine the temperature dependence of the
      electrical conductivity of DMPG dispersions at different concentrations,
      correlating the data with the corresponding differential scanning calorimetry
      (DSC) traces. Electrical conductivity together with electrophoretic mobility
      measurements allowed the calculation of the dependence of the degree of
      ionization of DMPG vesicles on lipid concentration and temperature. It was shown
      that there is a decrease in vesicle charge as the lipid concentration increases,
      which is probably correlated with the increase in the concentration of bulk
      Na(+). Apart from the known increase in the electrical conductivity along the
      DMPG temperature transition region, a sharp rise was observed at the bilayer
      pretransition for all lipid concentrations studied, possibly indicating that the
      beginning of the chain melting process is associated with an increase in bilayer
      ionization. It is confirmed here that the gel-fluid transition of DMPG at low
      ionic strength is accompanied by a huge increase in the dispersion viscosity.
      However, it is shown that this measured macroviscosity is distinct from the local
      viscosity felt by either charged ions or DMPG charged aggregates in measurements
      of electrical conductivity or electrophoretic mobility. Data presented here give
      support to the idea that DMPG vesicles, at low ionic strength, get more ionized
      along the temperature transition region and could be perforated and/or deformed
      vesicle structures.

PMID- 20669915
TI  - Nonionic-anionic mixed surfactants cubic mesophases. Part I: Structural
      chaotropic and kosmotropic effect.
AB  - We prepared and investigated cubic bicontinuous (V) phase from mixtures of
      nonionic monoolein (GMO) and anionic oleyl lactate (OL) surfactants in the
      presence of ethanol and water. The isotropic region and the composition of the V
      phase in the pseudoternary phase diagram vary with the nature of the hydrophilic
      headgroups and their charge. We examined three anionic species, acidic (HOL),
      partially neutralized (OL), and totally ionized (NaOL) forms. The largest swollen
      V region within the phase diagram was formed from the partially neutralized form.
      The V formation is dependent on the GMO/OL ratio. The largest isotropic region in
      the phase diagrams was found with GMO/OL at a 70:30 wt % ratio and in the
      presence of 5.0 and 38.5 wt % ethanol and water, respectively. The structural
      effect of OL was determined by small-angle X-ray spectroscopy, differential
      scanning calorimetry, and Fourier transform infrared. The results revealed that
      the structure is curvature-dependent. Mesophases made from 90:10 wt % GMO/OL
      showed phase transition from gyroid (G) to diamond (D) symmetry. Preparations
      made from 30:70 wt % GMO/OL exhibited coexistence of two mesophases, one (of low
      order) cubic and the other lamellar. Because of the overall gauche deformation
      growth, the hydrocarbon order decreased with the OL content increase. The GMO,
      sn(2) and sn(3) headgroups, and water structure vibration bands indicate a
      chaotropic effect as a result of the interdigitation of OL anions and Na(+) and
      H(+) counterions.

PMID- 20669917
TI  - The growth of structure I methane hydrate from molecular dynamics simulations.
AB  - The key factors that affect the growth of methane hydrates are identified using
      molecular dynamics simulations. The three-phase molecular models consisting of
      methane gas, liquid water, and solid hydrate phase are used in this study. The
      melting temperatures of such a model at different pressures are found to be in
      good agreement with experiment. The growth rate of methane hydrate is found to be
      dominated by (1) the solubility of methane in the liquid phase, (2) the
      diffusivity of methane in water, and (3) the adsorption of methane by methane
      filled incomplete water cages at the solid-liquid interface. The solubility, and
      hence the growth rate, increases with the partial pressure of methane in the
      vapor phase. The mass transport resistance from adsorption and the diffusion of
      methane are two competing factors, with the adsorption of methane at the
      interface found to be the rate-limiting step. The presence of a high
      concentration of incomplete clathrate hydrate cages presents strong affinity to
      dissolved methane at temperatures below the melting point. In addition to methane
      adsorption, water molecules must be expelled to form the complete clathrate
      cages. Both processes lead to a methane concentration minimum at 5-9 A in front
      of the growing interface. The methane concentration minimum provides the driving
      force for methane transport from the bulk to the interface. There are two types
      of solid layers of methane hydrate in the (1,0,0) direction. The growths of these
      layers are different, highly correlated, and affected by the methane
      concentration. A detailed mechanism of the layer growth is deduced from our
      simulations.

PMID- 20669916
TI  - Total synthesis and evaluation of phostriecin and key structural analogues.
AB  - Full details of the total synthesis of phostriecin (2), the assignment of its
      relative and absolute stereochemistry, and the resultant structural reassignment
      of the natural product previously represented as sultriecin (1), a phosphate
      versus sulfate monoester, are detailed. Studies with authentic material confirmed
      that phostriecin, but not sultriecin, is an effective and selective inhibitor of
      protein phosphatase 2A (PP2A) defining a mechanism of action responsible for its
      antitumor activity. The extension of the studies to the synthesis and evaluation
      of a series of key synthetic analogues is disclosed that highlights the
      importance of the natural product phosphate monoester (vs sulfate or free
      alcohol, both inactive and >250-fold), the alpha,beta-unsaturated lactone (12
      fold), and the hydrophobic Z,Z,E-triene tail (C12-C22, ca. 200-fold) including
      the unique importance of its unsaturation (50-fold, and no longer PP2A
      selective). 

PMID- 20669918
TI  - 2-Alkylmalonic acid: amphiphilic chelator and a potent inhibitor of
      metalloenzyme.
AB  - The present investigation demonstrates the potential of 2-alkylmalonic acid
      amphiphile as inhibitor of metalloenzymes like Taq DNA polymerase and alpha
      amylase. A dose-dependent inhibition of Taq DNA polymerase was observed when a
      polymerase chain reaction (PCR) was performed in the presence of amphiphiles
      while in the case of alpha-amylase the inhibition was found to be independent of
      the inhibitor concentration. Control experiments revealed that both the chelating
      as well as the amphiphilic nature of the inhibitor was essential for enzyme
      inhibition. The fluorescence intensity and lifetime of alpha-amylase were also
      found to decrease in the presence of the amphiphiles. Steady-state fluorescence
      quenching studies suggested that removal of the metal ion from the enzyme leads
      to a decrease in the solvent accessibility of tryptophans, indicating change in
      the tertiary structure of the protein. It is proposed that removal of metal ion
      from the active sites of the enzyme by the amphiphilic compound possibly leads to
      disruption of the native conformation of the enzyme which is responsible for loss
      of its activity.

PMID- 20669919
TI  - Enantioselective formal synthesis of (-)-englerin A via a Rh-catalyzed [4 + 3]
      cycloaddition reaction.
AB  - An enantioselective formal synthesis of (-)-englerin A (1) is reported. Key to
      the strategy is a Rh-catalyzed [4 + 3] cycloaddition reaction between furan 10
      and diazo ester 11 that, following an intramolecular aldol condensation, produces
      the tricyclic scaffold of englerin. This strategy also provides a rapid,
      efficient, and stereoselective access to the biologically significant core motif
      of the guaiane sesquiterpenes.

PMID- 20669920
TI  - Thermoresponsive nanohydrogels cross-linked by gold nanoparticles.
AB  - Thermoresponsive nanohydrogels cross-linked by gold nanoparticles (AuNPs) were
      prepared by 1,3-dipolar cycloaddition reactions and in situ reversible addition
      fragmentation chain-transfer (RAFT) polymerization. In order to synthesize
      thermoresponsive nanohydrogels, AuNPs decorated with azide groups (AuNPs-N(3))
      were prepared through ligand exchange. Click reactions between AuNPs-N(3) and
      dialkynetrithiocarbonate yielded cross-linked AuNP aggregates. The size and cross
      linking density of AuNP aggregates increased with the molar ratio of acetylene
      groups to azide groups. After click reactions, the absorption maximum of the
      plasmon band of AuNPs red-shifted to a long wavelength. Thermoresponsive
      nanohydrogels were prepared by in situ RAFT polymerization of N
      isopropylacrylamide (NIPAM) using trithiocarbonate in the cross-linked AuNP
      aggregates as chain-transfer agents. The thermoresponsive nanohydrogels presented
      a low critical solution temperature at around 32 degrees C due to the "coil-to
      globule" transition of connecting PNIPAM chains in the nanohydrogels. The size of
      the thermoresponsive nanohydrogels was determined by the molar ratio of acetylene
      groups to azide groups.

PMID- 20669921
TI  - Vibrational spectroscopy and theory of Fe(+)(CH(4))(n) (n = 1-4).
AB  - Vibrational spectra are measured for Fe(+)(CH(4))(n) (n = 1-4) in the C-H
      stretching region (2500-3200 cm(-1)) using photofragment spectroscopy. Spectra
      are obtained by monitoring CH(4) fragment loss following absorption of one photon
      (for n = 3, 4) or sequential absorption of multiple photons (for n = 1, 2). The
      spectra have a band near the position of the antisymmetric C-H stretch in
      isolated methane (3019 cm(-1)), along with bands extending >250 cm(-1) to the red
      of the symmetric C-H stretch in methane (2917 cm(-1)). The spectra are sensitive
      to the ligand configuration (eta(2) vs eta(3)) and to the Fe-C distance. Hybrid
      density functional theory calculations are used to identify possible structures
      and predict their vibrational spectra. The IR photodissociation spectrum shows
      that the Fe(+)(CH(4)) complex is a quartet, with an eta(3) configuration. There
      is also a small contribution to the spectrum from the metastable sextet eta(3)
      complex. The Fe(+)(CH(4))(2) complex is also a quartet with both CH(4) in an
      eta(3) configuration. For the larger clusters, the configuration switches from
      eta(3) to eta(2). In Fe(+)(CH(4))(3), the methane ligands are not equivalent.
      Rather, there is one short and two long Fe-C bonds, and each methane is bound to
      the metal in an eta(2) configuration. For Fe(+)(CH(4))(4), the calculations
      predict three low-lying structures, all with eta(2) binding of methane and very
      similar Fe-C bond lengths. No single structure reproduces the observed spectrum.
      The approximately tetrahedral C(1) ((4)A) structure contributes to the spectrum;
      the nearly square-planar D(2d) ((4)B(2)) and the approximately tetrahedral C(2)
      ((4)A) structure may contribute as well.

PMID- 20669922
TI  - Hyphenated technique for releasing and MALDI MS analysis of O-glycans in mucin
      type glycoprotein samples.
AB  - We developed an automatic apparatus for the release of O-glycans from mucin-type
      glycoproteins and proteoglycans (Matsuno, Y.-k.; Yamada, K.; Tanabe, A.;
      Kinoshita, M.; Maruyama, S.-z.; Osaka, Y.-s.; Masuko, T.; Kakehi, K. Anal.
      Biochem. 2007, 363, 245-257. Yamada, K.; Hyodo, S.; Matsuno, Y. K.; Kinoshita,
      M.; Maruyama, S. Z.; Osaka, Y. S.; Casal, E.; Lee, Y. C.; Kakehi, K. Anal.
      Biochem. 2007, 371, 52-61). The method allows rapid release of O-glycans as the
      reducing form within 10 min. In the present study, we connected the device to a
      MALDI-TOF MS spotter and achieved routine analysis of O-glycans in biological
      samples for clinical use after in situ derivatization of the released O-glycans
      with phenylhydrazine. We applied the method to the analysis of O-glycans
      expressed on MKN45 cells derived from human stomach cancer cells and found that
      MKN45 cells expressed characteristic trisialo-polylactosamine-type glycans as
      reported previously (Yamada, K.; Kinoshita, M.; Hayakawa, T.; Nakaya, S.; Kakehi,
      K. J. Proteome Res. 2009, 8, 521-537). We also applied the method to the analysis
      of O-glycans in serum samples. The present technique is the first attempt to use
      MS measurement for routine clinical diagnostic works.

PMID- 20669923
TI  - Designed molecular switches: controlling the conformation of benzamido
      diphenylacetylenes.
AB  - With the goal of creating a molecular switch, the hydrogen-bonded
      diphenylacetylene structure has been modified such that an equilibrium now exists
      between two intramolecular H-bonded states. Through X-ray crystallography and
      (1)H NMR analysis it is shown that this equilibrium can be biased in a
      predictable manner by modulating the relative acidity of the amide NH's.

PMID- 20669924
TI  - Insights into the nitric oxide reductase mechanism of flavodiiron proteins from a
      flavin-free enzyme.
AB  - Flavodiiron proteins (FDPs) catalyze reductive scavenging of dioxygen and nitric
      oxide in air-sensitive microorganisms. FDPs contain a distinctive non-heme
      diiron/flavin mononucleotide (FMN) active site. Alternative mechanisms for the
      nitric oxide reductase (NOR) activity consisting of either protonation of a
      diiron-bridging hyponitrite or "super-reduction" of a diferrous-dinitrosyl by the
      proximal FMNH(2) in the rate-determining step have been proposed. To test these
      alternative mechanisms, we examined a deflavinated FDP (deflavo-FDP) from
      Thermotoga maritima. The deflavo-FDP retains an intact diiron site but does not
      exhibit multiturnover NOR or O(2) reductase (O(2)R) activity. Reactions of the
      reduced (diferrous) deflavo-FDP with nitric oxide were examined by UV-vis
      absorption, EPR, resonance Raman, and FTIR spectroscopies. Anaerobic addition of
      nitric oxide up to one NO per diferrous deflavo-FDP results in formation of a
      diiron-mononitrosyl complex characterized by a broad S = (1)/(2 )EPR signal
      arising from antiferromagnetic coupling of an S = (3)/(2) {FeNO}(7) with an S = 2
      Fe(II). Further addition of NO results in two reaction pathways, one of which
      produces N(2)O and the diferric site and the other of which produces a stable
      diiron-dinitrosyl complex. Both NO-treated and as-isolated deflavo-FDPs regain
      full NOR and O(2)R activities upon simple addition of FMN. The production of
      N(2)O upon addition of NO to the mononitrosyl deflavo-FDP supports the
      hyponitrite mechanism, but the concomitant formation of a stable diiron
      dinitrosyl complex in the deflavo-FDP is consistent with a super-reduction
      pathway in the flavinated enzyme. We conclude that a diiron-mononitrosyl complex
      is an intermediate in the NOR catalytic cycle of FDPs.

PMID- 20669925
TI  - Electron affinities and electronic structures of o-, m-, and p-hydroxyphenoxyl
      radicals: a combined low-temperature photoelectron spectroscopic and Ab initio
      calculation study.
AB  - Hydroxyl substituted phenoxides, o-, m-, p-HO(C(6)H(4))O(-), and the
      corresponding neutral radicals are important species; in particular, the p-isomer
      pair, i.e., p-HO(C(6)H(4))O(-) and p-HO(C(6)H(4))O*, is directly involved in the
      proton-coupled electron transfer in biological photosynthetic centers. Here we
      report the first spectroscopic study of these species in the gas phase by means
      of low-temperature photoelectron spectroscopy (PES) and ab initio calculations.
      Vibrationally resolved PES spectra were obtained at 70 K and at several photon
      energies for each anion, directly yielding electron affinity (EA) and electronic
      structure information for the corresponding hydroxyphenoxyl radical. The EAs are
      found to vary with OH positions, from 1.990 +/- 0.010 (p) to 2.315 +/- 0.010 (o)
      and 2.330 +/- 0.010 (m) eV. Theoretical calculations were carried out to identify
      the optimized molecular structures for both anions and neutral radicals. The
      electron binding energies and excited state energies were also calculated to
      compare with experimental data. Excellent agreement is found between calculations
      and experiments. Molecular orbital analyses indicate a strong OH antibonding
      interaction with the phenoxide moiety for the o- as well as the p-isomer, whereas
      such an interaction is largely missing for the m-anion. The variance of EAs among
      three isomers is interpreted primarily due to the interplay between two competing
      factors: the OH antibonding interaction and the H-bonding stabilization (existed
      only in the o-anion).

PMID- 20669926
TI  - High-affinity interaction of poly(ADP-ribose) and the human DEK oncoprotein
      depends upon chain length.
AB  - Poly(ADP-ribose) polymerase-1 (PARP-1) is a molecular DNA damage sensor that
      catalyzes the synthesis of the complex biopolymer poly(ADP-ribose) (PAR) under
      consumption of NAD(+). PAR engages in fundamental cellular processes such as DNA
      metabolism and transcription and interacts noncovalently with specific binding
      proteins involved in DNA repair and regulation of chromatin structure. A factor
      implicated in DNA repair and chromatin organization is the DEK oncoprotein, an
      abundant and conserved constituent of metazoan chromatin, and the only member of
      its protein class. We have recently demonstrated that DEK, under stress
      conditions, is covalently modified with PAR by PARP-1, leading to a partial
      release of DEK into the cytoplasm. Additionally, we have also observed a
      noncovalent interaction between DEK and PAR, which we detail here. Using sequence
      alignment, we identify three functional PAR-binding sites in the DEK primary
      sequence and confirm their functionality in PAR binding studies. Furthermore, we
      show that the noncovalent binding to DEK is dependent on PAR chain length as
      revealed by an overlay blot technique and a PAR electrophoretic mobility shift
      assay. Intriguingly, DEK promotes the formation of a defined complex with a 54mer
      PAR (K(D) = 6 x 10(-8) M), whereas no specific interaction is detected with a
      short PAR chain (18mer). In stark contrast to covalent poly(ADP-ribosyl)ation of
      DEK, the noncovalent interaction does not affect the overall ability of DEK to
      bind to DNA. Instead the noncovalent interaction interferes with subsequent DNA
      dependent multimerization activities of DEK, as seen in South-Western,
      electrophoretic mobility shift, topology, and aggregation assays. In particular,
      noncovalent attachment of PAR to DEK promotes the formation of DEK-DEK complexes
      by competing with DNA binding. This was seen by the reduced affinity of PAR-bound
      DEK for DNA templates in solution. Taken together, our findings deepen the
      molecular understanding of the DEK-PAR interplay and support the existence of a
      cellular "PAR code" represented by PAR chain length.

PMID- 20669928
TI  - Infrared spectra and intensities of Ar-H(2)O and O(2)-H(2)O complexes in the
      range of the nu(3) band of H(2)O.
AB  - Infrared spectra and intensities of the nu(3) band of H(2)O in Ar-H(2)O and O(2)
      H(2)O complexes have been studied by helium nanodroplet spectroscopy. It was
      found that the H(2)O molecule rotates almost freely in both the Ar-H(2)O and O(2)
      H(2)O complexes. Infrared intensities of the nu(3) band of H(2)O in these
      complexes were equal to that of an isolated H(2)O molecule within experimental
      errors. The obtained infrared spectra and infrared intensities were compared with
      those of the N(2)-H(2)O complex in helium droplets, which we recently reported.

PMID- 20669929
TI  - Theoretical studies on the mechanisms and dynamics of OH radicals with
      CH(2)FCF(2)OCHF(2) and CH(2)FOCH(2)F.
AB  - The mechanisms and dynamics studies of the multichannel reactions of
      CH(2)FCF(2)OCHF(2) + OH (R1) and CH(2)FOCH(2)F + OH (R2) have been carried out
      theoretically. Three hydrogen abstraction channels and two displacement processes
      are found for reaction R1, whereas there are two hydrogen abstraction channels
      and one displacement process for reaction R2. The minimum energy paths are
      optimized at the B3LYP/6-311G(d,p) level, and the energy profiles are further
      refined by interpolated single-point energies (ISPE) method at the BMC-QCISD
      level of theory. By means of canonical variational transition state theory with
      small-curvature tunneling correction, the rate constants of reactions R1 and R2
      are obtained over the temperature range of 220-2000 K. The rate constants are in
      good agreement with the experimental data for reaction R1 and estimated data for
      reaction R2. The Arrhenius expression k(1) = 1.62 x 10(-20) T(2.75) exp(-1011/T)
      for reaction R1 and k(2) = 3.40 x 10(-21) T(3.04) exp(-384/T) for reaction R2
      over 220-2000 K are obtained. Furthermore, to further reveal the thermodynamics
      properties, the enthalpies of formation of reactants CH(2)FCF(2)OCHF(2),
      CH(2)FOCH(2)F, and the product radicals CHFCF(2)OCHF(2), CH(2)FCF(2)OCF(2), and
      CHFOCH(2)F are calculated by using isodesmic reactions.

PMID- 20669927
TI  - Medicinal chemistry as a conduit for the modulation of quorum sensing.

PMID- 20669930
TI  - Effect of [6]-shogaol on cytosolic Ca2+ levels and proliferation in human oral
      cancer cells (OC2).
AB  - The effect of [6]-shogaol (1) on cytosolic free Ca(2+) concentrations
      ([Ca(2+)](i)) and viability has not been explored previously in oral epithelial
      cells. The present study has examined whether 1 alters [Ca(2+)](i) and viability
      in OC2 human oral cancer cells. Compound 1 at concentrations > or = 5 microM
      increased [Ca(2+)](i) in a concentration-dependent manner with a 50% effective
      concentration (EC(50)) value of 65 microM. The Ca(2+) signal was reduced
      substantially by removing extracellular Ca(2+). In a Ca(2+)-free medium, the 1
      induced [Ca(2+)](i) elevation was mostly attenuated by depleting stored Ca(2+)
      with thapsigargin (an endoplasmic reticulum Ca(2+) pump inhibitor). The
      [Ca(2+)](i) signal was inhibited by La(3+) but not by L-type Ca(2+) channel
      blockers. The elevation of [Ca(2+)](i) caused by 1 in a Ca(2+)-containing medium
      was not affected by modulation of protein kinase C activity, but was inhibited by
      82% with the phospholipase A2 inhibitor aristolochic acid I (20 microM). U73122,
      a selective inhibitor of phospholipase C, abolished 1-induced [Ca(2+)](i)
      release. At concentrations of 5-100 microM, 1 killed cells in a concentration
      dependent manner. These findings suggest that [6]-shogaol induces a significant
      rise in [Ca(2+)](i) in oral cancer OC2 cells by causing stored Ca(2+) release
      from the thapsigargin-sensitive endoplasmic reticulum pool in an inositol 1,4,5
      trisphosphate-dependent manner and by inducing Ca(2+) influx via a phospholipase
      A2- and La(3+)-sensitive pathway.

PMID- 20669931
TI  - Low-lying structures and stabilities of large water clusters: investigation based
      on the combination of the AMOEBA potential and generalized energy-based
      fragmentation approach.
AB  - Based on a large database of local minima obtained with the polarizable AMOEBA
      potential, the generalized energy-based fragmentation (GEBF) approach is applied
      to locate low-lying structures of water clusters (H(2)O)(n) in the range n = 20
      30, at the B3LYP and MP2 levels. Our results show that the relative stabilities
      of isomers predicted by the AMOEBA empirical potential differ noticeably from
      those predicted by GEBF-B3LYP/6-311++G(d,p) and GEBF-MP2/6-311++G(3df,2p)
      calculations. From GEBF-B3LYP energies with zero-point vibrational energy
      corrections, one can see that for water clusters in the range n = 20-30 the
      transition from one-centered to two-centered cage structure occurs at n = 26.
      With increasing cluster size, the number of H-bonds per water molecule in the
      lowest-energy structures shows a gradually increasing trend, and the proportion
      of four-coordinated water molecules gradually increases, as expected for large
      water clusters. Based on GEBF-MP2/6-311++G(3df,2p) energies (instead of GEBF
      B3LYP/6-311++G(d,p) energies), different lowest-energy structures can be found
      for six cluster sizes in the range n = 20-30, suggesting the significance of the
      dispersion interaction in determining the relative energies of low-lying water
      clusters.

PMID- 20669932
TI  - Tirucallane-type alkaloids from the bark of Dysoxylum laxiracemosum.
AB  - Eight novel tirucallane-type alkaloids (1-8) and 11 known compounds were isolated
      from a methanol extract of the bark of Dysoxylum laxiracemosum. The structures of
      1-8 were elucidated using extensive NMR spectrometric and mass spectroscopic
      methods. Compounds 1 and 5, named laxiracemosins A and E, showed significant
      cytotoxicity against five human cancer cell lines.

PMID- 20669933
TI  - Antiplasmodial triterpenoids from the fruits of neem, Azadirachta indica.
AB  - Eight known and two new triterpenoid derivatives, neemfruitins A (9) and B (10),
      have been isolated from the fruits of neem, Azadirachta indica, a traditional
      antimalarial plant used by Asian and African populations. In vitro antiplasmodial
      tests evidenced a significant activity of the known gedunin and azadirone and the
      new neemfruitin A and provided useful information about the structure
      antimalarial activity relationships in the limonoid class.

PMID- 20669934
TI  - Functional and structural characterization of the 2/2 hemoglobin from
      Synechococcus sp. PCC 7002.
AB  - Cyanobacterium Synechococcus sp. PCC 7002 contains a single gene (glbN) coding
      for GlbN, a protein of the 2/2 hemoglobin lineage. The precise function of GlbN
      is not known, but comparison to similar 2/2 hemoglobins suggests that reversible
      dioxygen binding is not its main activity. In this report, the results of in
      vitro and in vivo experiments probing the role of GlbN are presented.
      Transcription profiling indicated that glbN is not strongly regulated under any
      of a large number of growth conditions and that the gene is probably
      constitutively expressed. High levels of nitrate, used as the sole source of
      nitrogen, and exposure to nitric oxide were tolerated better by the wild-type
      strain than a glbN null mutant, whereas overproduction of GlbN in the null mutant
      background restored the wild-type growth. The cellular contents of reactive
      oxygen/nitrogen species were elevated in the null mutant under all conditions and
      were highest under NO challenge or in the presence of high nitrate
      concentrations. GlbN overproduction attenuated these contents significantly under
      the latter conditions. The analysis of cell extracts revealed that the heme of
      GlbN was covalently bound to overproduced GlbN apoprotein in cells grown under
      microoxic conditions. A peroxidase assay showed that purified GlbN does not
      possess significant hydrogen peroxidase activity. It was concluded that GlbN
      protects cells from reactive nitrogen species that could be encountered naturally
      during growth on nitrate or under denitrifying conditions. The solution structure
      of covalently modified GlbN was determined and used to rationalize some of its
      chemical properties.

PMID- 20669935
TI  - Human DHX9 helicase unwinds triple-helical DNA structures.
AB  - Naturally occurring poly(purine.pyrimidine) rich regions in the human genome are
      prone to adopting non-canonical DNA structures such as intramolecular triplexes
      (i.e., H-DNA). Such structure-forming sequences are abundant and can regulate the
      expression of several disease-linked genes. In addition, the use of triplex
      forming oligonucleotides (TFOs) to modulate gene structure and function has
      potential as an approach to targeted gene therapy. Previously, we found that
      endogenous H-DNA structures can induce DNA double-strand breaks and promote
      genomic rearrangements. Herein, we find that the DHX9 helicase co
      immunoprecipitates with triplex DNA structures in mammalian cells, suggesting a
      role in the maintenance of genome stability. We tested this postulate by
      assessing the helicase activity of purified human DHX9 on various duplex and
      triplex DNA substrates in vitro. DHX9 displaced the third strand from a specific
      triplex DNA structure and catalyzed the unwinding with a 3' --> 5' polarity with
      respect to the displaced third strand. Helicase activity required a 3'-single
      stranded overhang on the third strand and was dependent on ATP hydrolysis. The
      reaction kinetics consisted of a pre-steady-state burst phase followed by a
      linear, steady-state pseudo-zero-order reaction. In contrast, very little if any
      helicase activity was detected on blunt triplexes, triplexes with 5'-overhangs,
      blunt duplexes, duplexes with overhangs, or forked duplex substrates. Thus,
      triplex structures containing a 3'-overhang represent preferred substrates for
      DHX9, where it removes the strand with Hoogsteen hydrogen-bonded bases. Our
      results suggest the involvement of DHX9 in maintaining genome integrity by
      unwinding mutagenic triplex DNA structures.

PMID- 20669936
TI  - Effective stabilization and delivery of siRNA: reversible siRNA-phospholipid
      conjugate in nanosized mixed polymeric micelles.
AB  - siRNA is a powerful tool to control cellular processes at the post
      transcriptional level. However, its therapeutic potential is limited because of
      low stability in biological fluids and the lack of simple and efficient delivery
      systems. Chemical modification of siRNA could be used to increase its
      intracellular delivery, but may affect its specific activity. To overcome these
      obstacles, we suggest a simple and effective system capable of stabilization,
      delivery, and subsequent release of free active siRNA within cells. With this in
      mind, we reversibly modified the double-stranded GFP-siRNA with a
      phosphothioethanol (PE) portion via the reducible disulfide bond and incorporated
      the resulting siRNA-S-S-PE conjugate in nanosized PEG-PE micelles. In the mixed
      siRNA-S-S-PE/PEG-PE micelles obtained, siRNA was well-protected against
      degradation by nucleases for at least 24 h, and was released easily from these
      nanoparticles in free form in the presence of glutathione (GSH) at a
      concentration mimicking the intracellular levels. In GFP-C166 endothelial cells,
      mixed GFP-siRNA-S-S-PE/PEG-PE micelles down-regulate the GFP production 50-fold
      more effectively than free siRNA. In addition, siRNA-containing micelles showed
      none of the cytotoxic side effects typical for siRNA delivery systems that are
      based on electrostatic association of siRNA with cationic carriers. Thus, a
      reversible siRNA-phospholipid conjugate formulated into mixed micelles with PEG
      PE can be an effective, nontoxic system for stabilization and delivery of siRNA.

PMID- 20669937
TI  - Protein mechanics: from single molecules to functional biomaterials.
AB  - Elastomeric proteins act as the essential functional units in a wide variety of
      biomechanical machinery and serve as the basic building blocks for biological
      materials that exhibit superb mechanical properties. These proteins provide the
      desired elasticity, mechanical strength, resilience, and toughness within these
      materials. Understanding the mechanical properties of elastomeric protein-based
      biomaterials is a multiscale problem spanning from the atomistic/molecular level
      to the macroscopic level. Uncovering the design principles of individual
      elastomeric building blocks is critical both for the scientific understanding of
      multiscale mechanics of biomaterials and for the rational engineering of novel
      biomaterials with desirable mechanical properties. The development of single
      molecule force spectroscopy techniques has provided methods for characterizing
      mechanical properties of elastomeric proteins one molecule at a time. Single
      molecule atomic force microscopy (AFM) is uniquely suited to this purpose.
      Molecular dynamic simulations, protein engineering techniques, and single
      molecule AFM study have collectively revealed tremendous insights into the
      molecular design of single elastomeric proteins, which can guide the design and
      engineering of elastomeric proteins with tailored mechanical properties.
      Researchers are focusing experimental efforts toward engineering artificial
      elastomeric proteins with mechanical properties that mimic or even surpass those
      of natural elastomeric proteins. In this Account, we summarize our recent
      experimental efforts to engineer novel artificial elastomeric proteins and
      develop general and rational methodologies to tune the nanomechanical properties
      of elastomeric proteins at the single-molecule level. We focus on general design
      principles used for enhancing the mechanical stability of proteins. These
      principles include the development of metal-chelation-based general methodology,
      strategies to control the unfolding hierarchy of multidomain elastomeric
      proteins, and the design of novel elastomeric proteins that exhibit stimuli
      responsive mechanical properties. Moving forward, we are now exploring the use of
      these artificial elastomeric proteins as building blocks of protein-based
      biomaterials. Ultimately, we would like to rationally tailor mechanical
      properties of elastomeric protein-based materials by programming the molecular
      sequence, and thus nanomechanical properties, of elastomeric proteins at the
      single-molecule level. This step would help bridge the gap between single protein
      mechanics and material biomechanics, revealing how the mechanical properties of
      individual elastomeric proteins are translated into the properties of macroscopic
      materials.

PMID- 20669938
TI  - Stable GM3 lactone mimetic raises antibodies specific for the antigens expressed
      on melanoma cells.
AB  - Immunotherapy of tumors and of melanoma in particular has a long history, and
      recently this therapeutic approach found a reliable scientific rationale. This
      biological therapy aims to teach the patient's immune system to recognize the
      antigens expressed on tumor cells and destroy them, leaving normal cells intact.
      The success of this therapy highly depends on the selection of target antigens
      that are essential for tumors growth and progression. The overexpression of GM(3)
      ganglioside 1 and especially the expression of its metabolite GM(3) lactone 2
      characterize murine and human melanomas, playing an important role in tumor
      progression and making such self-antigens potential targets for the immunotherapy
      of these neoplasms. Although more immunogenic than its precursor, GM(3) lactone 2
      is unsuitable to be used in immunotherapy as a melanoma-associated antigen (MAA)
      because it is unstable under physiological conditions. We designed and
      synthesized the hydrolytically stable mimetic 3, which is remarkably simpler than
      the native lactone 2; after conjugation of 3 to the protein carrier keyhole
      limpet hemocyanin (KLH), the obtained glycoprotein 5 was used as the immunogen in
      vivo to successfully elicit specific antimelanoma antibodies. In fact, no
      appreciable binding to GM(1) was observed. Capitalizing on the stability and on
      the reduced structural complexity of mimetic 3, the immunostimulant 5 we report
      represents a new promising synthetic glycoconjugate for the immunotherapy of
      melanoma.

PMID- 20669939
TI  - Fragmentation of trifluoromethylated alkenes and acetylenes by N,N
      binucleophiles. Synthesis of imidazolines or imidazolidines (oxazolidines)
      controlled by substituent.
AB  - The reaction of beta-halogeno-beta-polyfluoromethylstyrenes with N,N- or N,O
      binucleophiles leads to unexpected fragmentation products (imidazolines) or to
      heterocyclization giving CF(3)-substituted imidazolidines (N,N-) and oxazolidines
      (N,O-) depending on aryl substituent. The scope and the reaction mechanism are
      discussed.

PMID- 20669940
TI  - Approach for estimating microbial growth and biodegradation of hydrocarbon
      contaminants in subsoil based on field measurements: 2. Application in a field
      lysimeter experiment.
AB  - A new approach was applied to represent the natural attenuation of hydrocarbon
      (HC) contaminants as observed in a field lysimeter experiment. The approach
      describes the microbial growth on HC contaminants and linked HC biodegradation
      under natural precipitation conditions. The HC contaminants contained an inert
      component (n-dodecane) and soluble components (toluene, ethylbenzene, xylene
      isomers, and naphthalene), and their attenuation processes were predicted. The
      respiratory quinone profile method is used to indicate temporary changes in in
      situ microbial biomass possessed by HC-degrading microorganisms in soils. On the
      basis of field measurements conducted during the initial 92 days post-HC
      contamination, the kinetic parameters of HC-degrading microorganisms were
      estimated, which were used for the prediction of microbial growth and linked HC
      contaminant depletion in the contaminated soil for the subsequent 259 days. The
      prediction was in good agreement with the measured HC concentration and
      corresponding respiratory quinones from HC-degrading microorganisms. The results
      indicate that the proposed approach can provide a reliable prediction of HC
      depletion in subsoil on the basis of field measurements. Further efforts are
      expected to incorporate the approach into a multiphase flow and multicomponent
      transport model for application to actual HC-contaminated sites.

PMID- 20669941
TI  - Free radical reaction pathway, thermochemistry of peracetic acid homolysis, and
      its application for phenol degradation: spectroscopic study and quantum chemistry
      calculations.
AB  - The homolysis of peracetic acid (PAA) as a relevant source of free radicals
      (e.g., *OH) was studied in detail. Radicals formed as a result of chain radical
      reactions were detected with electron spin resonance and nuclear magnetic
      resonance spin trapping techniques and subsequently identified by means of the
      simulation-based fitting approach. The reaction mechanism, where a hydroxyl
      radical was a primary product of O-O bond rupture of PAA, was established with a
      complete assessment of relevant reaction thermochemistry. Total energy analysis
      of the reaction pathway was performed by electronic structure calculations (ab
      initio and semiempirical methods) at different levels and basis sets [e.g., HF/6
      311G(d), B3LYP/6-31G(d)]. Furthermore, the heterogeneous MnO2/PAA system was
      tested for the elimination of a model aromatic compound, phenol from aqueous
      solution. An artificial neural network (ANN) was designed to associate the
      removal efficiency of phenol with relevant process parameters such as
      concentrations of both the catalyst and PAA and the reaction time. Results were
      used to train and test ANN to identify an optimized network structure, which
      represented the correlations between the operational parameters and removal
      efficiency of phenol.

PMID- 20669942
TI  - The development of morphology and structure in hexagonal vaterite.
AB  - Inspired by the remarkable shapes and properties of CaCO(3) biominerals, many
      studies have investigated biomimetic routes aiming at synthetic equivalents with
      similar morphological and structural complexity. Control over the morphology of
      CaCO(3) crystals has been demonstrated, among other methods, by the use of
      additives that selectively allow the development of specific crystal faces, while
      inhibiting others. Both for biogenic and biomimetic CaCO(3), the crystalline
      state is often preceded by an amorphous precursor phase, but still limited
      information is available on the details of the amorphous-to-crystalline
      transition. By using a combination of cryoTEM techniques (bright field imaging,
      cryo-tomography, low dose electron diffraction and cryo-darkfield imaging), we
      show for the first time the details of this transition during the formation of
      hexagonal vaterite crystals grown in the presence of NH(4)(+) ions. The formation
      of hexagonal plate-like vaterite occurs via an amorphous precursor phase. This
      amorphous phase converts into the crystalline state through a solid state
      transformation in which order and morphology develop simultaneously. The mineral
      initially develops as polycrystalline vaterite which transforms into a single
      crystal directed by an NH(4)(+)-induced crystal plane that acts as a templating
      surface.

PMID- 20669943
TI  - Photomagnetic CoFe Prussian blue analogues: role of the cyanide ions as active
      electron transfer bridges modulated by cyanide-alkali metal ion interactions.
AB  - X-ray absorption spectra at the Co L(2,3)-edges were analyzed by means of ligand
      field multiplet calculations in different states of three photomagnetic CoFe
      Prussian blue analogues of chemical formula Cs(2)Co(4)[Fe(CN)(6)](3.3) x 11
      H(2)O, Rb(2)Co(4)[Fe(CN)(6)](3.3) x 11 H(2)O and Na(2)Co(4)[Fe(CN)(6)](3.3) x 11
      H(2)O. These simulations of the experimental spectra allowed the quantification
      of the crystal field parameter (10Dq). This determination led us (i) to evidence
      different behaviors of the Co(III)(LS) and Co(II)(HS) ions in the three
      dimensional structure related to their electronic configurations, (ii) to propose
      an approach based on the electronic density distribution along the Co-NC-Fe
      linkage to account for the energy position of the states implied in the switching
      properties of the compounds, and (iii) to explain the different photomagnetic
      properties observed as a function of the size of the inserted alkali cation by
      competing interactions between the cyanide ion and the transition metal ions
      within the CoFe cyanide bimetallic network on the one hand and the cyanide ion
      and the alkali metal ions on the other hand.

PMID- 20669944
TI  - Electrochemical stability of elemental metal nanoparticles.
AB  - The corrosion behavior of nanometer-scale solids is important in applications
      ranging from sensing to catalysis. Here we present a general thermodynamic
      analysis of this for the case of elemental metals and use the analysis to
      demonstrate the construction of a particle-size-dependent potential-pH diagram
      for the case of platinum. We discuss the data set required for the construction
      of such diagrams in general and describe how some parameters are accessible via
      experiment while others can only be reliably determined from first-principles
      based electronic structure calculations. In the case of Pt, our analysis predicts
      that particles of diameter less than approximately 4 nm dissolve via the direct
      electrochemical dissolution pathway, Pt --> Pt(2+) + 2e(-), while larger
      particles form an oxide. As an extension of previously published work by our
      group, electrochemical scanning tunneling microscopy is used to examine the
      stability of individual Pt-black particles with diameters ranging from 1 to 10
      nm. Our experimental results confirm the thermodynamic predictions, suggesting
      that our analysis provides a general framework for the assessment of the
      electrochemical stability of nanoscale elemental metals.

PMID- 20669945
TI  - Transition from tunneling to hopping in single molecular junctions by measuring
      length and temperature dependence.
AB  - The charge transport characteristics of a family of long conjugated molecular
      wires have been studied using the scanning tunneling microscope break junction
      technique. The family consists of four wires ranging from 3.1 to 9.4 nm in
      length. The two shortest wires show highly length dependent and temperature
      invariant conductance behavior, whereas the longer two wires show weakly length
      dependent and temperature variant behavior. This trend is consistent with a model
      whereby conduction occurs by two different mechanisms in the family of wires: by
      a coherent tunneling mechanism in the shorter two and by an incoherent charge
      hopping process in the longer wires. The temperature dependence of the two
      conduction mechanisms gives rise to a phenomenon whereby at elevated temperatures
      longer molecules that conduct via charge hopping can yield a higher conductance
      than shorter wires that conduct via tunneling. The evolution of molecular
      junctions as the tip retracts has been studied and explained in context of the
      characteristics of individual transient current decay curves.

PMID- 20669946
TI  - Bacterial chemotaxis in linear and nonlinear steady microfluidic gradients.
AB  - Diffusion-based microfluidic devices can generate steady, arbitrarily shaped
      chemical gradients without requiring fluid flow and are ideal for studying
      chemotaxis of free-swimming cells such as bacteria. However, if microfluidic
      gradient generators are to be used to systematically study bacterial chemotaxis,
      it is critical to evaluate their performance with actual quantitative chemotaxis
      tests. We characterize and compare three diffusion-based gradient generators by
      confocal microscopy and numerical simulations, select an optimal design and apply
      it to chemotaxis experiments with Escherichia coli in both linear and nonlinear
      gradients. Comparison of the observed cell distribution along the gradients with
      predictions from an established mathematical model shows very good agreement,
      providing the first quantification of chemotaxis of free-swimming cells in steady
      nonlinear microfluidic gradients and opening the door to bacterial chemotaxis
      studies in gradients of arbitrary shape.

PMID- 20669947
TI  - A coiled-coil enabled split-luciferase three-hybrid system: applied toward
      profiling inhibitors of protein kinases.
AB  - The 518 protein kinases encoded in the human genome are exquisitely regulated and
      their aberrant function(s) are often associated with human disease. Thus, in
      order to advance therapeutics and to probe signal transduction cascades, there is
      considerable interest in the development of inhibitors that can selectively
      target protein kinases. However, identifying specific compounds against such a
      large array of protein kinases is difficult to routinely achieve utilizing
      traditional activity assays, where purified protein kinases are necessary. Toward
      a simple, rapid, and practical method for identifying specific inhibitors, we
      describe the development and application of a split-protein methodology utilizing
      a coiled-coil-assisted three-hybrid system. In this approach, a protein kinase of
      interest is attached to the C-terminal fragment of split-firefly luciferase and
      the coiled-coil Fos, which is specific for the coiled-coil Jun, is attached to
      the N-terminal fragment. Upon addition of Jun conjugated to a pan-kinase
      inhibitor such as staurosporine, a three-hybrid complex is established with
      concomitant reassembly of the split-luciferase enzyme. An inhibitor can be
      potentially identified by the commensurate loss in split-luciferase activity by
      displacement of the modified staurosporine. We demonstrate that this new three
      hybrid approach is potentially general by testing protein kinases from the
      different kinase families. To interrogate whether this method allows for
      screening inhibitors, we tested six different protein kinases against a library
      of 80 known protein kinase inhibitors. Finally, we demonstrate that this three
      hybrid system can potentially provide a rapid method for structure/function
      analysis as well as aid in the identification of allosteric inhibitors.

PMID- 20669948
TI  - Conserved binding mode of human beta2 adrenergic receptor inverse agonists and
      antagonist revealed by X-ray crystallography.
AB  - G protein-coupled receptors (GPCRs) represent a large fraction of current
      pharmaceutical targets, and of the GPCRs, the beta(2) adrenergic receptor
      (beta(2)AR) is one of the most extensively studied. Previously, the X-ray crystal
      structure of beta(2)AR has been determined in complex with two partial inverse
      agonists, but the global impact of additional ligands on the structure or local
      impacts on the binding site are not well-understood. To assess the extent of such
      ligand-induced conformational differences, we determined the crystal structures
      of a previously described engineered beta(2)AR construct in complex with two
      inverse agonists: ICI 118,551 (2.8 A), a recently described compound (2.8 A)
      (Kolb et al, 2009), and the antagonist alprenolol (3.1 A). The structures show
      the same overall fold observed for the previous beta(2)AR structures and
      demonstrate that the ligand binding site can accommodate compounds of different
      chemical and pharmacological properties with only minor local structural
      rearrangements. All three compounds contain a hydroxy-amine motif that
      establishes a conserved hydrogen bond network with the receptor and chemically
      diverse aromatic moieties that form distinct interactions with beta(2)AR.
      Furthermore, receptor ligand cross-docking experiments revealed that a single
      beta(2)AR complex can be suitable for docking of a range of antagonists and
      inverse agonists but also indicate that additional ligand-receptor structures may
      be useful to further improve performance for in-silico docking or lead
      optimization in drug design.

PMID- 20669949
TI  - Amorphous precursors in the nucleation of clathrate hydrates.
AB  - The nucleation and growth of clathrate hydrates of a hydrophobic guest comparable
      to methane or carbon dioxide are studied by molecular dynamics simulations of two
      phase systems. The crystallization proceeds in two steps: First, the guest
      molecules concentrate in "blobs", amorphous clusters involving multiple guest
      molecules in water-mediated configurations. These blobs are in dynamic
      equilibrium with the dilute solution and give birth to the clathrate cages that
      eventually transform it into an amorphous clathrate nucleus. In a second step,
      the amorphous clathrate transforms into crystalline clathrate. At low
      temperatures, the system can be arrested in the metastable amorphous clathrate
      phase for times sufficiently long for it to appear as an intermediate in the
      crystallization of clathrates. The "blob mechanism" unveiled in this work
      synthesizes elements of the labile cluster and local structuring hypotheses of
      clathrate nucleation and bears strong analogies to the two-step mechanisms of
      crystallization of proteins and colloids.

PMID- 20669950
TI  - Kinetic isotope effects for RNA cleavage by 2'-O- transphosphorylation:
      nucleophilic activation by specific base.
AB  - To better understand the interactions between catalysts and transition states
      during RNA strand cleavage, primary (18)O kinetic isotope effects (KIEs) and
      solvent D(2)O isotope effects were measured to probe the mechanism of base
      catalyzed 2'-O-transphosphorylation of the RNA dinucleotide 5'-UpG-3'. The
      observed (18)O KIEs for the nucleophilic 2'-O and in the 5'-O leaving group at pH
      14 are both large relative to reactions of phosphodiesters with good leaving
      groups, indicating that the reaction catalyzed by hydroxide has a transition
      state (TS) with advanced phosphorus-oxygen bond fission to the leaving group
      ((18)k(LG) = 1.034 +/- 0.004) and phosphorus-nucleophile bond formation
      ((18)k(NUC) = 0.984 +/- 0.004). A breakpoint in the pH dependence of the 2'-O
      transphosphorylation rate to a pH independent phase above pH 13 has been
      attributed to the pK(a) of the 2'-OH nucleophile. A smaller nucleophile KIE is
      observed at pH 12 ((18)k(NUC) = 0.995 +/- 0.004) that is interpreted as the
      combined effect of the equilibrium isotope effect (ca. 1.02) on deprotonation of
      the 2'-hydroxyl nucleophile and the intrinsic KIE on the nucleophilic addition
      step (ca. 0.981). An alternative mechanism in which the hydroxide ion acts as a
      general base is considered unlikely given the lack of a solvent deuterium isotope
      effect above the breakpoint in the pH versus rate profile. These results
      represent the first direct analysis of the transition state for RNA strand
      cleavage. The primary (18)O KIE results and the lack of a kinetic solvent
      deuterium isotope effect together provide strong evidence for a late transition
      state and 2'-O nucleophile activation by specific base catalysis.

PMID- 20669951
TI  - Compositional analysis of lignocellulosic feedstocks. 1. Review and description
      of methods.
AB  - As interest in lignocellulosic biomass feedstocks for conversion into
      transportation fuels grows, the summative compositional analysis of biomass, or
      plant-derived material, becomes ever more important. The sulfuric acid hydrolysis
      of biomass has been used to measure lignin and structural carbohydrate content
      for more than 100 years. Researchers have applied these methods to measure the
      lignin and structural carbohydrate contents of woody materials, estimate the
      nutritional value of animal feed, analyze the dietary fiber content of human
      food, compare potential biofuels feedstocks, and measure the efficiency of
      biomass-to-biofuels processes. The purpose of this paper is to review the history
      and lineage of biomass compositional analysis methods based on a sulfuric acid
      hydrolysis. These methods have become the de facto procedure for biomass
      compositional analysis. The paper traces changes to the biomass compositional
      analysis methods through time to the biomass methods currently used at the
      National Renewable Energy Laboratory (NREL). The current suite of laboratory
      analytical procedures (LAPs) offered by NREL is described, including an overview
      of the procedures and methodologies and some common pitfalls. Suggestions are
      made for continuing improvement to the suite of analyses.

PMID- 20669952
TI  - Compositional analysis of lignocellulosic feedstocks. 2. Method uncertainties.
AB  - The most common procedures for characterizing the chemical components of
      lignocellulosic feedstocks use a two-stage sulfuric acid hydrolysis to
      fractionate biomass for gravimetric and instrumental analyses. The uncertainty
      (i.e., dispersion of values from repeated measurement) in the primary data is of
      general interest to those with technical or financial interests in biomass
      conversion technology. The composition of a homogenized corn stover feedstock
      (154 replicate samples in 13 batches, by 7 analysts in 2 laboratories) was
      measured along with a National Institute of Standards and Technology (NIST)
      reference sugar cane bagasse, as a control, using this laboratory's suite of
      laboratory analytical procedures (LAPs). The uncertainty was evaluated by the
      statistical analysis of these data and is reported as the standard deviation of
      each component measurement. Censored and uncensored versions of these data sets
      are reported, as evidence was found for intermittent instrumental and equipment
      problems. The censored data are believed to represent the "best case" results of
      these analyses, whereas the uncensored data show how small method changes can
      strongly affect the uncertainties of these empirical methods. Relative standard
      deviations (RSD) of 1-3% are reported for glucan, xylan, lignin, extractives, and
      total component closure with the other minor components showing 4-10% RSD. The
      standard deviations seen with the corn stover and NIST bagasse materials were
      similar, which suggests that the uncertainties reported here are due more to the
      analytical method used than to the specific feedstock type being analyzed.

PMID- 20669953
TI  - Catalytic and regioselective ring expansion of arylcyclobutanones with
      trimethylsilyldiazomethane. Ligand-dependent entry to beta-ketosilane or
      enolsilane adducts.
AB  - Divergent reactivity is uncovered in the homologation of arylcyclobutanones with
      trimethylsilyldiazomethane. With Sc(OTf)(3) as catalyst, enolsilanes are obtained
      with a high preference for methylene migration. By contrast, Sc(hfac)(3) gives
      beta-ketosilanes with both regio- and diastereocontrol. Each adduct affords the
      cyclopentanone upon hydrolysis.

PMID- 20669954
TI  - Nitric oxide synthase stabilizes the tetrahydrobiopterin cofactor radical by
      controlling its protonation state.
AB  - Nitric oxide synthase (NOS), a homodimeric enzyme with a flavin reductase domain
      and a P450-type heme-containing oxygenase domain, catalyzes the formation of NO
      from L-arginine, NADPH, and O(2) in a two-step reaction sequence. In the first
      step, a tetrahydrobiopterin (H(4)B) cofactor bound near one of the heme
      propionate groups acts as an electron donor to the P450-type heme active site,
      yielding a one-electron oxidized radical that is subsequently re-reduced. In
      solution, H(4)B undergoes two-electron oxidation, showing that the enzyme
      significantly alters the proton- and electron-transfer properties of the
      cofactor. Multifrequency EPR and ENDOR spectroscopy were used to determine
      magnetic parameters, and from them the (de)protonation state of the H(4)B radical
      in the oxygenase domain dimer of inducible NO synthase that was trapped by rapid
      freeze quench. From 9.5 and 330-416 GHz EPR and from 34 GHz (1)H ENDOR
      spectroscopy, the g tensor of the radical and the hyperfine tensors of several N
      and H nuclei in the radical were obtained. Density functional theory calculations
      at the PBE0/EPR-II level for H(4)B radical models predict different spin density
      distributions and g and hyperfine tensors for different protonation states.
      Comparison of the predicted and experimental values leads to the conclusion that
      the radical is cationic H(4)B(*+), suggesting that NOS stabilizes this protonated
      form to utilize the cofactor in a unique dual one-electron redox role, where it
      can deliver an electron to the active site for reductive oxygen activation and
      also remove an electron from the active site to generate NO and not NO(-). The
      protein environment also prevents further oxidation and subsequent loss of
      function of the cofactor, thus enabling the enzyme to perform the unusual
      catalytic one-electron chemistry.

PMID- 20669955
TI  - Ferro- and antiferromagnetic coupling switch accompanied by twist deformation
      around the copper(II) and nitroxide coordination bond.
AB  - Two novel copper(II) complexes with tert-butyl 2-pyridyl nitroxide (2pyNO(*)),
      [Cu(2+)(2pyNO(-))(2pyNO(*))](2)(BF(4)(-))(2) (1 x BF(4)) and [Cu(2+)(2pyNO(
      ))(2pyNO(*))](2)(ClO(4)(-))(2) (1 x ClO(4)), were prepared and structurally
      characterized. They contained mixed-valent ligands from 2pyNO, whose oxygen atoms
      were located at equatorial positions of the copper ion. The [Cu(2+)(2pyNO(
      ))(2pyNO(*))] unit was dimerized by mu-oxo bridges of the anion ligand, giving a
      zigzag linear spin system involving four paramagnetic S = 1/2 centers. The two
      compounds are isomorphous in an orthorhombic Pbca space group. Magnetic study
      revealed that 1 x ClO(4) showed ferromagnetic copper-radical coupling in all
      temperature ranges investigated here. On the other hand, 1 x BF(4) exhibited a
      structural phase transition at 64 K, where the magnetic susceptibility was
      drastically dropped on cooling. The copper-radical magnetic couplings were
      characterized as ferro- and antiferromagnetic for the high- and low-temperature
      phases, respectively. The crystallographic analysis clarified that the nitroxide
      oxygen atom remained at the equatorial position throughout the single-crystal-to
      single-crystal phase transition, while the previously known spin-transition-like
      copper-radical compounds showed conversion of the roles of equatorial and axial
      positions. The orthogonal arrangement between the copper d sigma and nitroxide
      pi* orbitals is essential for the ferromagnetic coupling, and a slight
      dislocation of the radical oxygen atom from the chelate plane leads to violation
      of the orthogonal orbital arrangement, giving a practically diamagnetic low
      temperature phase.

PMID- 20669956
TI  - Quercetin and ferulic acid aggravate renal carcinoma in long-term diabetic
      victims.
AB  - Many phytoantioxidants have therapeutic drawbacks due to their potent prooxidant
      bioactivity. It is hypothesized that phytoantioxidants (PAO) are beneficial only
      to the early-stage diabetes mellitus (DM) and will become ineffective once
      renopathy occurs. Gallic acid, rutin, EGCG, ferulic acid (FA), and quercetin were
      tried on the streptozotocin (STZ)-induced DM rat model for a 28 week experimental
      period. All of these PAO were shown to be ineffective for hypoglycemic action.
      The incidence of cataract (50%), injured glomerules, and renal cell carcinoma
      (RCC) was very common, among which the most severely affected involved the
      quercetin- and the FA-treated groups. The tumorigenicity of ferulic acid is still
      unclear. However, for quercetin, this can be attributted to (i) the prooxidant
      effect, (ii) the insulin-secretagogue bioactivity, and (iii) the competitive and
      noncompetitive inhibition on the O-methyltransferase to enhance the estradiol
      induced tumorigenesis. Conclusively, quercetin and FA are able to aggravate, if
      not induce, nephrocarcinoma. It is time to reevaluate the tumorigenic detrimental
      effect of PAO, especially those exhibiting prooxidant bioactivity.

PMID- 20669957
TI  - A practical protocol for the highly E-selective formation of aryl-substituted
      silylketene acetals.
AB  - The E/Z-selectivity in the formation of silylketene acetals derived from
      phenylacetate esters, mediated by LiHMDS, has been studied by in situ NMR
      techniques. The formation is seen to be highly E-selective with use of the newly
      developed protocol. Isolated aryl-substituted silylketene acetals are now
      attainable with high levels of E-geometrical purity in excellent yield.

PMID- 20669958
TI  - Diels-Alder chemistry of siloles and their transformation into cyclohex-2-ene-1,4
      cis-diols.
AB  - The synthesis of siloles with substitution patterns that are continuative toward
      natural product synthesis are described. Their reactivity in Diels-Alder
      chemistry was explored through thermal, Lewis acid, and high-pressure reactions.
      Furthermore, bicyclic adducts were oxidatively cleaved to reveal a highly
      functionalized cyclohexene core.

PMID- 20669959
TI  - Cr(VI) removal on fungal biomass of Neurospora crassa: the importance of
      dissolved organic carbons derived from the biomass to Cr(VI) reduction.
AB  - Interactions of toxic Cr(VI) with renewable biomaterials are considered an
      important pathway for Cr(VI) removal in ecosystems. Biomaterials are susceptible
      to dissolution, and their dissolved derivatives may provide an alternative to
      surface-involved pathway for scavenging of Cr(VI). In this study, dissolved
      organic carbon (DOC) derived from Neurospora crassa biomass was investigated. The
      proportion of Cr(VI) reduction by DOC to that on biomass was determined to
      evaluate the importance of DOC to Cr(VI) reduction. A rapid increase in DOC
      concentration from 145.6 to 193.7 mg L(-1) was observed when N. crassa-biomass
      was immersed in 0.01 M KCl solution at pH of 1-5, and polysaccharides, peptides,
      and glycoproteins with carboxyl, amide, and -NH functional groups, are the major
      compositions of DOC. On reaction of 96.2 microM Cr(VI) with N. crassa-biomass or
      DOC, it was estimated that DOC contributed approximately 53.8-59.5% of the total
      Cr(VI) reduction on biomass in the dark. Illumination enhanced Cr(VI) reduction
      via photo-oxidation of biomass/DOC under aeration conditions, which formed
      superoxide for Cr(VI) reduction. At pH 1, photoinduced Cr(VI) reduction by DOC
      proceeded more rapidly than reduction on the biomass surface. However, at pH >3,
      with a decrease in Cr(VI) reduction by DOC, photon-excited biomass may become an
      important electron source for Cr(VI) photoreduction.

PMID- 20669960
TI  - X-ray crystallographic structure of an artificial beta-sheet dimer.
AB  - This paper describes the X-ray crystallographic structure of a designed cyclic
      beta-sheet peptide that forms a well-defined hydrogen-bonded dimer that mimics
      beta-sheet dimers formed by proteins. The 54-membered ring macrocyclic peptide
      (1a) contains molecular template and turn units that induce beta-sheet structure
      in a heptapeptide strand that forms the dimerization interface. The X-ray
      crystallographic structure reveals the structures of the two "Hao" amino acids
      that help template the beta-sheet structure and the two delta-linked ornithine
      turn units that link the Hao-containing template to the heptapeptide beta-strand.
      The Hao amino acids adopt a conformation that resembles a tripeptide in a beta
      strand conformation, with one edge of the Hao unit presenting an alternating
      array of hydrogen-bond donor and acceptor groups in the same pattern as that of a
      tripeptide beta-strand. The delta-linked ornithines adopt a conformation that
      resembles a hydrogen-bonded beta-turn, in which the ornithine takes the place of
      the i+1 and i+2 residues. The dimers formed by macrocyclic beta-sheet 1a resemble
      the dimers of many proteins, such as defensin HNP-3, the lambda-Cro repressor,
      interleukin 8, and the ribonuclease H domain of HIV-1 reverse transcriptase. The
      dimers of 1a self-assemble in the solid state into a barrel-shaped trimer of
      dimers in which the three dimers are arranged in a triangular fashion. Molecular
      modeling in which one of the three dimers is removed and the remaining two dimers
      are aligned face-to-face provides a model of the dimers of dimers of closely
      related macrocyclic beta-sheet peptides that were observed in solution.

PMID- 20669961
TI  - Cholesterol in bilayers with PUFA chains: doping with DMPC or POPC results in
      sterol reorientation and membrane-domain formation.
AB  - Using neutron diffraction Harroun et al. [(2006) Biochemistry 45, 1227-1233;
      (2008) Biochemistry 47, 7090-7096] carried out studies that unequivocally
      demonstrated cholesterol preferentially sequestering in the middle of bilayers
      (i.e., flat orientation) made of lipids with polyunsaturated fatty acids (PUFA),
      in contrast to its "usual" position where its hydroxyl group locates near the
      lipid/water interface (i.e., upright orientation). Here we clearly show, using
      neutron diffraction, cholesterol's orientational preference in different lipid
      bilayers. For example, although it requires 50 mol % POPC (16:0-18:1 PC) in DAPC
      (di20:4 PC) bilayers to cause cholesterol to revert to its upright orientation,
      only 5 mol % DMPC (di14:0 PC) is needed to achieve the same effect. This result
      demonstrates not only cholesterol's affinity for saturated hydrocarbon chains,
      but also its aversion for PUFAs. Molecular dynamics (MD) simulations performed on
      similar systems show that in high PUFA content bilayers cholesterol is
      simultaneously capable of assuming different orientations within a bilayer.
      Although this result is known from previous MD studies by Marrink et al. [(2008)
      J. Am. Chem. Soc. 130, 10-11], it has yet to be confirmed experimentally.
      Importantly, MD simulations predict the formation of DMPC-rich domains, data
      corroborated by experiment (i.e., 10 mol % DMPC-doped DAPC bilayers), where
      cholesterol preferentially locates in its upright orientation, while in DMPC
      depleted domains cholesterol is found mostly in the bilayer center (i.e., flat
      orientation). These results lend credence to DMPC's aversion for PUFAs,
      supporting the notion that domain formation is primarily driven by lipids.

PMID- 20669962
TI  - Which one among aspartyl protease, metallopeptidase, and artificial
      metallopeptidase is the most efficient catalyst in peptide hydrolysis?
AB  - In this comparative DFT study, the hydrolysis of a peptide bond (Phe1-Phe2) by
      the following three types of catalysts has been studied: (1) beta-secretase
      (BACE2), (2) matrix metalloproteinase (MMP) and insulin degrading enzyme (IDE),
      and (3) [Pd(H(2)O)(4)](2+) (I(MPC)) and [Pd(2)(mu-OH)([18]aneN(6))](3+) (I(DPC)).
      The computed energetics predict that among these catalysts, the Zn(2+) metal
      center containing MMP is the most efficient in catalyzing this reaction. The two
      active site aspartate residues containing BACE2 catalyze this reaction with 5.0
      kcal/mol higher barrier than MMP. The substitution of a His ligand with Glu in
      the metal center of MMP generates the active site of IDE that catalyzes the
      reaction with a 6.9 kcal/mol higher barrier than MMP. Both artificial peptidases
      I(MPC) and I(DPC) catalyze this reaction with significantly high barriers of 35.4
      and 31.0 kcal/mol, respectively. The computed energetics of all the catalysts are
      in line with the available experimental and theoretical data.

PMID- 20669963
TI  - Estradiol binding prevents ApoB-100 misfolding in electronegative LDL(-).
AB  - Seeking for a modified lipoprotein present in plasma that could account for the
      atherogenic effect of high cholesterol, several years ago electronegative LDL(-)
      was identified. The peculiar feature of LDL(-) is an apoprotein misfolding that
      triggers the formation of aggregates, perfectly fitting in size the
      subendothelial droplets observed in early phases of atherogenesis. Apoprotein
      misfolding was therefore proposed as a possible atherogenic modification. LDL(-)
      can be spontaneously produced in vitro by plasma incubation through phospholipid
      hydrolysis catalyzed by the activity of endogenous phospholipases. As a
      consequence, apoprotein is misfolded. 17beta-Estradiol (E2), a specific ligand to
      apoB-100, was used to unravel the relationship between negative charge of the
      lipoprotein and apoprotein structural/conformational shift. Although E2 addition
      to plasma does not prevent LDL(-) generation nor phospholipase activity, it
      deeply stabilizes apoB-100 structure, thus preventing its structural and
      conformational shift. Apoprotein stabilization extends to lipids. Indeed, while a
      loosening of lipid packing is observed together with apoprotein misfolding,
      conversely, when E2 stabilizes apoprotein, lipid structure is preserved. Finally,
      even in the presence of LDL(-), the E2-stabilized LDL is resistant to
      aggregation, unambiguously demonstrating that misfolding, but not negative
      charge, primes aggregation. In conclusion, electronegative charge and misfolding
      are independent and distinct features of LDL(-), and apoprotein misfolding rather
      than the increase in the negative charge emerges both as a valid biomarker and as
      an appealing pharmacological and nutritional target.

PMID- 20669964
TI  - Synthesis of multivalent tuberculosis and Leishmania-associated capping
      carbohydrates reveals structure-dependent responses allowing immune evasion.
AB  - Mycobacterium tuberculosis and the protozoan parasites of the genus Leishmania
      are intracellular pathogens that can survive in macrophages--the very white blood
      cells of the immune system responsible for engulfing and ultimately clearing
      foreign invaders. The ability of these pathogens to hide within immune cells has
      made the design of effective therapies, including vaccines, to control
      tuberculosis and leishmaniasis particularly challenging. Herein we present the
      synthesis and development of carbohydrate-based probes to demonstrate that
      changes in pathogen-associated surface oligosaccharides are sufficient to alter
      cellular immune responses and thereby let a pathogen hide from immune
      surveillance.

PMID- 20669965
TI  - [NiII(3-OMe-salophene)]: a potent agent with antitumor activity.
AB  - In this study, we investigated the anticancer properties of methoxy-substituted
      nickel(II)(salophene) derivatives. We demonstrated that the most active complex
      [NiII(3-OMe-salophene)] is not necrotic in Burkitt-like lymphoma cells (BJAB) and
      human B-cell precursor cells (Nalm-6). [NiII(3-OMe-salophene)] inhibited
      proliferation and induced apoptosis in a concentration dependent manner, giving
      evidence for the involvement of CD95 receptor-mediated, extrinsic pathway.
      Furthermore, [NiII(3-OMe-salophene)] overcame vincristine drug resistance in BJAB
      and Nalm-6 cells.

PMID- 20669966
TI  - A "zero sample concentration approach": standardization of methods for the
      estimation of total antioxidant activity by the use of extrapolation to zero
      sample concentration. A novel standard. 1. ABTS cation radical scavenging.
AB  - The study presents the general method of standardization of estimations of total
      antioxidant activity (TAA) by extrapolating parameters to zero sample
      concentration based on a pseudo-first-order kinetics model. To test its
      suitability, the method was applied to the ABTS cation radical scavenging assay,
      as the first choice. Two alternative methods of extrapolation were presented, via
      linear regression and numerical fitting to the dose-response profile. An
      extrapolation method gives the highest value of estimates, independent of sample
      concentration, and creates a new standard approach to the methods of TAA
      estimation. It is proposed to designate the modified index as "standard
      equivalent antioxidant capacity at zero" (SEAC0) or TEAC0 (for Trolox as
      standard). The examples of estimates for some foods and rat plasma are presented
      and compared with the literature method. The applicability of the extrapolation
      approach to the other TAA measurement methods is under evaluation.

PMID- 20669967
TI  - Mechanism of fast proton transport along one-dimensional water chains confined in
      carbon nanotubes.
AB  - A reactive molecular dynamics simulation employing the multistate empirical
      valence bond (MS-EVB) methodology is reported for the hydration structure of an
      excess proton in a (6,6) carbon nanotube as well as for the mechanism of proton
      transport (PT) within the nanoconfined environment. The proton is found to be
      hydrated in a distorted Zundel cation (H(5)O(2)(+)) form within the one
      dimensional, confined water chain. Proton transfer events occur via a "Zundel
      Zundel" mechanism through a transient H(7)O(3)(+) intermediate that differs
      significantly from the "Eigen-Zundel-Eigen" mechanism found in bulk water.

PMID- 20669969
TI  - Use of artificial stomach-duodenum model for investigation of dosing fluid effect
      on clinical trial variability.
AB  - Lilly Compound X (LCX) is an oncology drug that was tested in a phase I clinical
      study using starch blend capsules. The drug was given to a small patient
      population (4 patients) and showed large inter- and intra-patient variability. In
      order to evaluate the possible effect of stomach pH on exposure and ways to
      mitigate the variability issue, artificial stomach-duodenum (ASD) experiments
      were conducted to investigate the hypothesis that carefully selected dosing
      fluids would have an impact in minimizing exposure variability caused by the
      formulation, which could lead to more consistent evaluation of drug absorption in
      patients. The ASD data corroborates the observed variability, and was a good tool
      to investigate the effect of stomach pH and potential dosing solutions on
      duodenal concentrations. Administering capsules co-formulated with Captisol (10%
      drug load) along with Sprite was shown by the ASD to be an effective way to
      increase duodenal concentrations as well as to reduce the difference between
      duodenal concentrations for different gastric pH. The reduction in variability of
      duodenum AUC (in ASD) is expected to correlate well with a reduction of
      variability in patient exposure. The dosing regimen of Sprite/Captisol is
      therefore suggested for future clinical trials involving LCX. Furthermore, for
      design of early phase clinical trials, ASD technology can be used to assist in
      choosing the proper dosing solution to mitigate absorption and exposure
      variability issues.

PMID- 20669970
TI  - Glycan encapsulated gold nanoparticles selectively inhibit shiga toxins 1 and 2.
AB  - Shiga toxins (Stx) released by Escherichia coli O157:H7 and Shigella dysentriae
      cause life-threatening conditions that include hemolytic uremic syndrome (HUS),
      kidney failure, and neurological complications. Cellular entry is mediated by the
      B-subunit of the AB(5) toxin, which recognizes cell surface glycolipids present
      in lipid raft-like structures. We developed gold glyconanoparticles that present
      a multivalent display similar to the cell surface glycolipids to compete for
      these toxins. These highly soluble glyconanoparticles were nontoxic to the Vero
      monkey kidney cell line and protected Vero cells from Stx-mediated toxicity in a
      dose-dependent manner. The inhibition is highly dependent on the structure and
      density of the glycans; selective inhibition of Stx1 and the more clinically
      relevant Stx2 was achieved. Interestingly, natural variants of Stx2, Stx2c, and
      Stx2d possessing minimal amino acid variation in the receptor binding site of the
      B-subunit or changes in the A-subunit were not neutralized by either the Stx1- or
      Stx2-specific gold glyconanoparticles. Our results suggest that tailored
      glyconanoparticles that mimic the natural display of glycans in lipid rafts could
      serve as potential therapeutics for Stx1 and Stx2. However, a few amino acid
      changes in emerging Stx2 variants can change receptor specificity, and further
      research is needed to develop receptor mimics for the emerging variants of Stx2.

PMID- 20669971
TI  - Comparison of antioxidant activities of different colored wheat grains and
      analysis of phenolic compounds.
AB  - Extracts from six wheat varieties (three purple, one yellow, two red, and one
      white) were evaluated and compared for their antioxidant capacities against
      oxygen radical and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical. Phenolic
      composition in the extracts was examined by high-performance liquid
      chromatography and mass spectrometry. The results showed that Charcoal purple
      wheat had remarkable antioxidant activity (up to 6899 MUmol/100 g) followed by
      Red Fife wheat and yellow Luteus wheat. White AC Vista wheat, due to its lowest
      phenolic content, exhibited the weakest antioxidant property. The major phenolic
      composition identified in wheat grains consisted of phenolic acids, flavones,
      flavonols, and anthocyanins. The former three components were detected in all of
      the wheat varieties, whereas anthocyanins were identified only in purple wheat.
      Therefore, anthocyanins could be the major compounds distinguishing purple wheats
      from other colored wheats with high antioxidant activity.

PMID- 20669972
TI  - Non-peptide macrocyclic histone deacetylase inhibitors derived from tricyclic
      ketolide skeleton.
AB  - Inhibition of histone deacetylase (HDAC) function is a validated therapeutic
      strategy for cancer treatment. Of the several structurally distinct small
      molecule histone deacetylase inhibitors (HDACi) reported, macrocyclic
      depsipeptides possess the most complex cap groups and have demonstrated excellent
      HDAC inhibition potency and isoform selectivity. Unfortunately, the development
      of macrocyclic depsipeptides has been hampered in part because of development
      problems characteristic of large peptides and the complex reaction schemes
      required for their synthesis. Herein we report that tricyclic ketolide TE-802 is
      an excellent mimetic for the peptide backbone of macrocyclic HDACi. Compounds
      derived from this template are particularly selective against HDACs 1 and 2 with
      nanomolar inhibitory activity. Interrogation of the association between a subset
      of these compounds and key HDAC isoforms, using AutoDock, enables a molecular
      description of the interaction between the HDAC enzyme's outer rim and the
      inhibitors' macrocyclic cap group that are responsible for compound affinity and
      presumably isoform selectivity.

PMID- 20669973
TI  - MEK inhibition potentiates the activity of Hsp90 inhibitor 17-AAG against
      pancreatic cancer cells.
AB  - The Ras/Raf/MEK/ERK signaling has been implicated in uncontrolled cell
      proliferation and tumor progression in pancreatic cancer. The purpose of this
      study is to evaluate the antitumor activity of MEK inhibitor U0126 in combination
      with Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) in
      pancreatic cancer cells. Western blotting showed that 17-AAG caused a 2- to 3
      fold transient activation of MEK/ERK signaling in pancreatic cancer cells. The
      activation sustained for 6 h before phospho-ERK (p-ERK) destabilization. The
      selective MEK inhibitor U0126 completely abolished 17-AAG induced ERK1/2
      activation and resulted in more than 80% of phospho-ERK degradation after only 15
      min treatment. Moreover, U0126 had complementary effect on 17-AAG regulated
      oncogenic and cell cycle related proteins. Although 17-AAG downregulated cyclin
      D1, cyclin E, CDK4 and CDK6, it led to cyclin A and CDK2 accumulation, which was
      reversed by the addition of U0126. Antiproliferation assay showed that
      combination of U0126 and 17-AAG resulted in synergistic cytotoxic effect. More
      importantly, 17-AAG alone only exhibited moderate inhibition of cell migration in
      vitro, while addition of U0126 dramatically enhanced the inhibitory effect by 2-
      to 5-fold. Taken together, these data demonstrate that MEK inhibitor U0126
      potentiates the activity of Hsp90 inhibitor 17-AAG against pancreatic cancer
      cells. The combination of Hsp90 and MEK inhibition could provide a promising
      avenue for the treatment of pancreatic cancer.

PMID- 20669974
TI  - Synthesis, processing and solid state excipient interactions of cucurbit[6]uril
      and its formulation into tablets for oral drug delivery.
AB  - The synthesis, processing, and solid state excipient interactions of
      cucurbit[6]uril (CB[6]) and its formulation into oral tablets has been examined
      using a range of physical chemistry techniques. Rapid precipitation from HCl by
      the addition of water yields microcrystalline CB[6] with smaller and more
      consistent particle size (30-165 MUm) compared with the sieved CB[6] (50-540 MUm)
      produced from large crystals grown by slow evaporation from HCl. The
      microcrystalline particles also contain fewer water molecules in the crystal
      compared with the sieved particles: 10 and 16% respectively. Microcrystalline
      CB[6] can be formulated into tablets suitable for oral delivery with a CB[6]
      content of 1-50% w/w, with the other excipients including lactose, talc, Avicel,
      magnesium stearate and Ac-Di-Sol. In the solid state microcrystalline CB[6] does
      not interact significantly with the talc, Ac-Di-Sol or Avicel, but significant
      interactions are observed when mixed or ground with either magnesium stearate or
      lactose, resulting in the lowering of the melting points of both excipients. This
      work represents the first study of the physical processing and solid state
      chemistry of CB[n]s for pharmaceutical formulation and represents an important
      development step in the use of CB[n]s as drug delivery vehicles.

PMID- 20669975
TI  - Electron transfer-oxygen transfer oxygenation of sulfides catalyzed by the
      H5PV2Mo10O40 polyoxometalate.
AB  - The oxygenation of sulfides to the corresponding sulfoxides catalyzed by
      H(5)PV(2)Mo(10)O(40) and other acidic vanadomolybdates has been shown to proceed
      by a low-temperature electron transfer-oxygen transfer (ET-OT) mechanism. First,
      a sulfide reacts with H(5)PV(2)Mo(10)O(40) to yield a cation radical-reduced
      polyoxometalate ion pair, R(2)(+*),H(5)PV(IV)V(V)Mo(10)O(40), that was identified
      by UV-vis spectroscopy (absorptions at 650 and 887 nm for PhSMe(+*) and
      H(5)PV(IV)V(V)Mo(10)O(40)) and EPR spectroscopy (quintet at g = 2.0079, A = 1.34
      G for the thianthrene cation radical and the typical eight-line spectrum for
      V(IV)). Next, a precipitate is formed that shows by IR the incipient formation of
      the sulfoxide and by EPR a VO(2+) moiety supported on the polyoxometalate.
      Dissolution of this precipitate releases the sulfoxide product. ET-OT oxidation
      of diethylsulfide yielded crystals containing [V(O)(OSEt(2))(x)(solv)(5-x)](2+)
      cations and polyoxometalate anions. Under aerobic conditions, catalytic cycles
      can be realized with formation of mostly sulfoxide (90%) but also some disulfide
      (10%) via carbon-sulfide bond cleavage.

PMID- 20669976
TI  - Carbon nanotubes reorganize actin structures in cells and ex vivo.
AB  - The ability of globular actin to form filaments and higher-order network
      structures of the cytoskeleton is essential for cells to maintain their shape and
      perform essential functions such as force generation, motility, and division.
      Alterations of actin structures can dramatically change a cell's ability to
      function. We found that purified and dispersed single wall carbon nanotubes
      (SWCNTs) can induce actin bundling in cells and in purified model actin systems.
      SWCNTs do not induce acute cell death, but cell proliferation is greatly reduced
      in SWCNT-treated cells with an increase in actin-related division defects. Actin,
      normally present in basal stress fibers in control cells, is located in
      heterogeneous structures throughout the SWCNT-treated cell. These SWCNT-induced
      changes in actin structures are seen functionally in multinucleated cells and
      with reduced force generation. Ex vivo, purified actin filaments cross-linked
      with alpha-actinin and formed isotropic networks, whereas SWCNTs caused purified
      actin filaments to assemble into bundles. While purified, isolated SWCNTs do not
      appear acutely toxic, this subcellular reorganization may cause chronic changes
      to cellular functions.

PMID- 20669978
TI  - Copper-catalyzed intramolecular N-arylation of quinazolinones: facile convergent
      approach to (-)-circumdatins H and J.
AB  - A copper-catalyzed intramolecular N-arylation of a quinazolinone nucleus that
      furnished the central benzodiazepine core unit has been demonstrated to
      accomplish an efficient convergent total synthesis of (-)-circumdatins H and J.

PMID- 20669977
TI  - Comparison of cyclooxygenase-1 crystal structures: cross-talk between monomers
      comprising cyclooxygenase-1 homodimers.
AB  - Prostaglandin endoperoxide H synthases (PGHSs)-1 and -2 (also called
      cyclooxygenases (COXs)-1 and -2) catalyze the committed step in prostaglandin
      biosynthesis. Both isoforms are targets of nonsteroidal antiinflammatory drugs
      (NSAIDs). PGHSs are homodimers that exhibit half-of-sites COX activity; moreover,
      some NSAIDs cause enzyme inhibition by binding only one monomer. To learn more
      about the cross-talk that must be occurring between the monomers comprising each
      PGHS-1 dimer, we analyzed structures of PGHS-1 crystallized under five different
      conditions including in the absence of any tightly binding ligand and in the
      presence of nonspecific NSAIDs and of a COX-2 inhibitor. When crystallized with
      substoichiometric amounts of an NSAID, both monomers are often fully occupied
      with inhibitor; thus, the enzyme prefers to crystallize in a fully occupied form.
      In comparing the five structures, we only observe changes in the positions of
      residues 123-129 and residues 510-515. In cases where one monomer is fully
      occupied with an NSAID and the partner monomer is incompletely occupied, an
      alternate conformation of the loop involving residues 123-129 is seen in the
      partially occupied monomer. We propose, on the basis of this observation and
      previous cross-linking studies, that cross-talk between monomers involves this
      mobile 123-129 loop, which is located at the dimer interface. In ovine PGHS-1
      crystallized in the absence of an NSAID, there is an alternative route for
      substrate entry into the COX site different than the well-known route through the
      membrane binding domain.

PMID- 20669979
TI  - Copper-catalyzed synthesis of N-fused heterocycles through regioselective 1,2
      aminothiolation of 1,1-dibromoalkenes.
AB  - The first aminothiolation of 1,1-dibromoalkene is described using an inexpensive
      copper/N,N-dimethylethylenediamine catalyst. The method provides a powerful means
      of using easily available 1,1-dihaloalkenes as precursors to fused heterocycles.

PMID- 20669980
TI  - Electronic properties of the biphenylene sheet and its one-dimensional
      derivatives.
AB  - We have studied the electronic properties and relative stability of the
      biphenylene sheet composed of alternating eight-, six- and four-carbon rings and
      its one-dimensional derivatives including ribbons and tubes of different widths
      and morphologies by means of density functional theory calculations. The two
      dimensional sheet presents a metallic character that is also present in the
      planar strips with zigzag-type edges. Armchair-edged strips develop a band gap
      that decreases monotonically with the ribbon width. The narrowest armchair strip
      considered here (0.62 nm wide) presents a large band gap of 1.71 eV, while the
      2.14 nm wide armchair strip exhibits a band gap of 0.08 eV. We have also found
      that tubes made by rolling these ribbons in a seamlessly manner are all metallic,
      independent of their chirality. However, while the calculated energy landscape
      suggests that planar strips present a relative stability comparable to that of
      C(60), in the tubular form, they present a more pronounced metastable nature with
      a Gibbs free energy of at least 0.2 eV per carbon higher than in C(60).

PMID- 20669981
TI  - Hydrogen-bond-induced heteroassembly in binary colloidal systems.
AB  - A new binary colloidal system is designed with each colloidal component being
      able to exclusively interact with the colloids of the second component,
      respectively. The colloids are based on cross-linked polystyrene and polymerized
      by means of surfactant-free emulsion polymerization with either 4-hydroxyl
      styrene or 4-vinyl pyridine as comonomers. The comonomers are selected to
      decorate the colloids with complementary H-bond donors or acceptors.
      Characterization of the colloids by light scattering in CHCl(3) results in
      particle radii covering a regime of 130 nm < R < 270 nm and indicates a narrow
      particle size distribution for all prepared samples. The colloids are slightly
      swollen compared to their state in H(2)O. The corresponding size ratio expressed
      as the radius of the small colloids divided by the radius of the large colloids
      in CHCl(3) extends over a regime of 0.52 < R(S)/R(L) < 0.85. IR analysis
      indicates strong hydrogen bonds between a colloidal component and the
      complementary molecular functions, that is, phenol or pyridine. If both colloidal
      components are directly combined as suspension in CHCl(3) a fast
      heteroaggregation is observed. This aggregation slows down and becomes accessible
      to an analysis by means of time-resolved static light scattering if the
      suspensions get sufficiently dilute. Fast aggregation can be totally inhibited if
      capping agents like phenol to cap the 4-vinyl pyridine functions are added as
      highly concentrated solutions. Dried samples of those binary suspensions
      equilibrated with an appropriate amount of phenol show the first indication for
      an ordered binary assembly.

PMID- 20669982
TI  - Multicompartment core/shell microgels.
AB  - Multiresponsive poly(N-isopropylacrylamide-co-acrylic acid) (pNIPAm-AAc)
      microgels containing mechanically and thermodynamically decoupled poly(N
      isopropylmethacrylamide) (pNIPMAm) cores have been prepared. To achieve this
      structure, pNIPMAm microgels were used as templates in the synthesis of an N,N'
      (1,2-dihydroxyethylene)bisacrylamide (DHEA) cross-linked pNIPMAm inner shell. A
      pNIPAm-AAc outer shell was then added, resulting in "core/double-shell"
      microgels. Erosion of the inner shell via periodate-mediated cleavage of the 1,2
      diol bond in DHEA produced multiresponsive core/shell microgels with independent
      cores. The striking structural changes and unique multiresponsivity achieved in
      microgels prepared via this approach illustrate the potential of multifunctional,
      multicomponent delivery vehicles that do not suffer from antagonistic
      interferences arising when different functional components are introduced within
      a single particle.

PMID- 20669984
TI  - Atmospheric oxidation of tetrachloroethylene: an ab initio study.
AB  - A number of experimental studies have been conducted to determine the atmospheric
      oxidation of tetrachloroethylene, many indicating phosgene as the major product.
      Although various mechanisms have been suggested, the mechanism of phosgene
      production is unclear. Additionally, confusion has arisen over the role chlorine
      atoms may play in the oxidation of tetrachloroethylene and the products produced.
      To clarify these points, this study presents a comprehensive computational study
      of both the hydroxyl radical and the chlorine atom initiated atmospheric
      oxidation mechanism of tetrachloroethylene. The energetics for the oxidation of
      tetrachloroethylene (C(2)Cl(4)) are computed using ab initio methods. Potential
      energy surfaces of the reaction pathways are determined from the computations.
      This study clarifies the involvement of the Cl-initiated reaction pathways in the
      oxidation of tetrachloroethylene. Results from this work suggest that the final
      products are primarily from the Cl-initiated oxidation and include:
      trichloroacetyl chloride [ClC(O)CCl(3)], phosgene [C(O)Cl(2)], and regeneration
      of the initiating chlorine atom.

PMID- 20669983
TI  - Effects of 7-O substitutions on estrogenic and anti-estrogenic activities of
      daidzein analogues in MCF-7 breast cancer cells.
AB  - Daidzein (1) is a natural estrogenic isoflavone. We report here that 1 can be
      transformed into anti-estrogenic ligands by simple alkyl substitutions of the 7
      hydroxyl hydrogen. To test the effect of such structural modifications on the
      hormonal activities of the resulting compounds, a series of daidzein analogues
      have been designed and synthesized. When MCF-7 cells were treated with the
      analogues, those resulting from hydrogen substitution by isopropyl (3d), isobutyl
      (3f), cyclopentyl (3g), and pyrano- (2) inhibited cell proliferation, estrogen
      induced transcriptional activity, and estrogen receptor (ER) regulated
      progesterone receptor (PgR) gene expression. However, methyl (3a) and ethyl (3b)
      substitutions of the hydroxyl proton only led to moderate reduction of the
      estrogenic activities. These results demonstrated the structural requirements for
      the transformation of daidzein from an ER agonist to an antagonist. The most
      effective analogue, 2, was found to reduce in vivo estrogen stimulated MCF-7 cell
      tumorigenesis using a xenograft mouse model.

PMID- 20669985
TI  - Oligonucleotide incorporation and base pair stability of 9-deaza-2'
      deoxyguanosine, an analogue of 8-oxo-2'-deoxyguanosine.
AB  - 9-Deaza-2'-deoxyguanosine (CdG) is a C-nucleoside and an analogue of the abundant
      promutagen 8-oxo-2'-deoxyguanosine (OdG). Like 2'-deoxyguanosine (dG), CdG should
      form a stable base pair with dC, but similar to OdG, CdG contains an N7-hydrogen
      that should allow it to also form a relatively stable base pair with dA. In order
      to further investigate the base pairing of CdG, it was incorporated into DNA and
      paired with either dC or dA. Melting studies revealed CdG:dC base pairs are less
      stable than dG:dC base pairs, while CdG:dA base pairs are less stable than OdG:dA
      base pairs. In order to gain a deeper understanding of these results, quantum
      studies on model structures of nucleoside monomers and base pairs were performed,
      the results of which indicate that (i) CdG:dC base pairs are likely destabilized
      relative to dG:dC as a result of structural constraints imposed by the C
      nucleotide character of CdG, and (ii) CdG:dA base pairs may be less stable than
      OdG:dA base pairs, at least in part, because of a third long-range interaction
      that is possible in OdG:dA but not in CdG:dA.

PMID- 20669986
TI  - Characterization of glutathione conjugates of duloxetine by mass spectrometry and
      evaluation of in silico approaches to rationalize the site of conjugation for
      thiophene containing drugs.
AB  - The in vitro bioactivation of the selective serotonin and norepinephrine reuptake
      inhibitor duloxetine was investigated using liver microsomes and cytosol,
      expressed glutathione transferase, and recombinant P450 2D6 and 1A2. In the
      presence of glutathione, several conjugates were identified and characterized
      using a combination of direct infusion nanoelectrospray mass spectrometry on an
      LTQ/Orbitrap and liquid-chromatography mass spectrometry on a triple quadrupole.
      Structural characterization of these conjugates revealed that glutathione
      conjugation occurred on naphthalene rather than on thiophene and likely proceeded
      via a reactive epoxide intermediate. Experiments with recombinant P450s and the
      isoform specific inhibitors quinidine and furafylline suggested that both P450
      2D6 and 1A2 were involved in the bioactivation of duloxetine. To explore the
      utility of in silico approaches to address bioactivation issues, MetaSite and two
      docking approaches (rigid and induced-fit docking) utilizing publicly available
      human P450 crystal structures or a homology model for P450 2C19 were used to
      predict the sites of bioactivation for duloxetine as well as the thiophene
      containing compounds tienilic acid, suprofen, ticlopidine, methapyrilene, and OSI
      930 for which glutathione conjugates on the thiophene moiety have been reported.
      MetaSite and induced fit docking but not rigid docking correctly predicted that
      naphthalene rather than thiophene was the preferred site of bioactivation for
      duloxetine by P450 2D6. MetaSite predictions were also consistent with literature
      reports that thiophene was the site of glutathione conjugation for tienilic acid,
      suprofen, and OSI-930 but not for ticlopidine or methapyrilene. Of the two
      docking approaches investigated, induced fit docking results were consistent with
      thiophene as the site of bioactivation for all compounds to which it was applied.
      In conclusion, our investigation identified the likely bioactivation pathway for
      duloxetine and demonstrated the utility of in silico approaches MetaSite and
      induced fit docking to address potential bioactivation liabilities.

PMID- 20669987
TI  - Association of Alix with late endosomal lysobisphosphatidic acid is important for
      dengue virus infection in human endothelial cells.
AB  - The most severe form of dengue virus (DENV) infection is dengue hemorrhagic
      fever/dengue shock syndrome (DHF/DSS), which is accompanied by increased vascular
      permeability indicating that endothelial cells are the targets of DENV infection.
      However, molecular mechanisms underlying DENV replication in endothelial cells
      remained poorly understood. We therefore examined changes in subcellular
      proteomes of different cellular compartments (including cytosolic,
      membrane/organelle, nucleus, and cytoskeleton) of human endothelial (EA.hy926)
      cells upon DENV2 infection using a 2-DE-based proteomics approach followed by Q
      TOF MS and MS/MS. A total of 35 altered proteins were identified in these
      subcellular locales, including an increase in the level of Alix (apoptosis-linked
      gene-2-interacting protein X) in the cytosolic fraction of DENV2-infected cells
      compared to mock control cells. Double immunofluorescence staining revealed
      colocalization of Alix with late endosomal lysobisphosphatidic acid (LBPA). This
      complex has been proposed to be involved in the export of DENV proteins from late
      endosomes to the cytoplasm. Subsequent functional study revealed that
      pretreatment with an anti-LBPA antibody prior to DENV challenge significantly
      reduced the level of viral envelope protein synthesis and DENV replication. Our
      data indicate that Alix plays a pivotal role in the early phase of DENV
      replication, particularly when it arrives at the late endosome stage. Blocking
      this step may lead to a novel therapeutic approach to reducing the level of DENV
      replication in vivo.

PMID- 20669988
TI  - Quantitative proteome and transcriptome analysis of the archaeon Thermoplasma
      acidophilum cultured under aerobic and anaerobic conditions.
AB  - A comparative proteome and transcriptome analysis of Thermoplasma acidophilum
      cultured under aerobic and anaerobic conditions has been performed. One-thousand
      twenty-five proteins were identified covering 88% of the cytosolic proteome.
      Using a label-free quantitation method, we found that approximately one-quarter
      of the identified proteome (263 proteins) were significantly induced (>2 fold)
      under anaerobic conditions. Thirty-nine macromolecular complexes were identified,
      of which 28 were quantified and 15 were regulated under anaerobiosis. In
      parallel, a whole genome cDNA microarray analysis was performed showing that the
      expression levels of 445 genes were influenced by the absence of oxygen.
      Interestingly, more than 40% of the membrane protein-encoding genes (145 out of
      335 ORFs) were up- or down-regulated at the mRNA level. Many of these proteins
      are functionally associated with extracellular protein or peptide degradation or
      ion and amino acid transport. Comparison of the transcriptome and proteome showed
      only a weak positive correlation between mRNA and protein expression changes,
      which is indicative of extensive post-transcriptional regulatory mechanisms in T.
      acidophilum. Integration of transcriptomics and proteomics data generated
      hypotheses for physiological adaptations of the cells to anaerobiosis, and the
      quantitative proteomics data together with quantitative analysis of protein
      complexes provide a platform for correlation of MS-based proteomics studies with
      cryo-electron tomography-based visual proteomics approaches.

PMID- 20669990
TI  - Accurate determination of protein secondary structure content from Raman and
      Raman optical activity spectra.
AB  - Raman spectroscopy measures molecular vibrations triggered by the inelastic
      scattering of light, while Raman optical activity (ROA) measures a small
      difference in the Raman scattering from chiral molecules using circularly
      polarized light. We used Raman or ROA spectra to determine the secondary
      structure contents (helix, sheet, or other) of proteins. Forty-four ROA and 24
      Raman protein spectra were converted into mean intensities within 10 cm(-1) width
      bins. The partial least squares algorithm with 5-fold cross-validation was used
      to construct models to give secondary structure contents from spectral data. The
      optimized algorithm gives highly accurate secondary structure contents, with R(2)
      and rmsd values of 0.99, and 0.6-1.7%, respectively, for second derivative Raman
      data when comparing predicted to experimental data. Using ROA data from 620 to
      1850 cm(-1) is almost as accurate. Analysis of amide I, II, and III and backbone
      spectral regions reveals the importance of each of these regions for secondary
      structure assignment. Raman and ROA may be the methods of choice for rapid
      measurement of protein secondary structure contents, since they have
      unprecedented accuracy.

PMID- 20669991
TI  - Identification of racemization sites using deuterium labeling and tandem mass
      spectrometry.
AB  - Racemization of amino acids is a common chemical degradation pathway observed in
      biopharmaceuticals and is particularly prevalent in synthetic peptides. The
      identification of racemized amino acid residue(s) by mass spectrometry is
      particularly challenging due to isobaric mass between the isomeric forms. In this
      paper, we present a novel methodology combining stable deuterium labeling with
      collisionally induced dissociation-tandem mass spectrometry (CID-MS/MS) to
      elucidate racemized amino acid residues in immunoglobulin samples. Immunoglobulin
      G subclasses IgG1, IgG2, and IgG4 samples were first stressed in protonated or
      deuterated buffer (pH 8 or 9) at 40 or 50 degrees C storage for days or weeks.
      These forced degraded samples were reduced, S-carbamidomethylated, and digested
      with trypsin in protonated solution, and the tryptic digests were then analyzed
      via liquid chromatography/mass spectrometry (LC-MS) or sequenced via liquid
      chromatography/tandem mass spectrometry (LC-MS/MS) to detect racemized peptides
      and elucidate the location of racemized amino acid residues. The methodology
      successfully identified several racemized amino acid residues in the constant
      region of the heavy chains of the three IgG subclasses. Although the IgG
      subclasses have very similar primary protein sequences, our results interestingly
      indicated different racemization rates for specific amino acid residues.

PMID- 20669992
TI  - Electroosmotic sampling. Application to determination of ectopeptidase activity
      in organotypic hippocampal slice cultures.
AB  - We hypothesize that peptide-containing solutions pulled through tissue should
      reveal the presence and activity of peptidases in the tissue. Using the natural
      zeta-potential in the organotypic hippocampal slice culture (OHSC), physiological
      fluids can be pulled through the tissue with an electric field. The hydrolysis of
      the peptides present in the fluid drawn through the tissue can be determined
      using capillary HPLC with electrochemical detection of the biuret complexes of
      the peptides following a postcolumn reaction. We have characterized this new
      sampling method by measuring the flow rate, examining the use of internal
      standards, and examining cell death caused by sampling. The sampling flow rate
      ranges from 60 to 150 nL/min with a 150 microm (ID) sampling capillary with an
      electric field (at the tip of the capillary) from 30 to 60 V/cm. Cell death can
      be negligible with controlled sampling conditions. Using this sampling approach,
      we have electroosmotically pulled Leu-enkephalin through OHSCs to identify
      ectopeptidase activity in the CA3 region. These studies show that a bestatin
      sensitive aminopeptidase may be critical for the hydrolysis of exogenous Leu
      enkephalin, a neuropeptide present in the CA3 region of OHSCs.

PMID- 20669993
TI  - Differentiation and semiquantitative analysis of an isoaspartic acid in human
      alpha-Crystallin by postsource decay in a curved field reflectron.
AB  - Alpha-Crystallin, which forms a huge multimeric complex that is essential for
      maintaining eye lens transparency, is one of the major proteins in the lens. The
      protein, which exists as isoforms alphaA and alphaB, functions as a molecular
      chaperone to restore the original conformations of distorted constituent proteins
      in the lens. This function is important to maintain the transparency of the lens,
      because there is no protein turnover in the lens. Abnormal aggregation of
      constituent proteins in the lens has been reported in cataract patients, and
      deamidation of Asn as well as racemization and isomerization of Asp have been
      found in the alpha-Crystallin of these patients. While the establishment of a
      quick and facile analytical method is eagerly anticipated to investigate the
      relevance of the isomerization to pathological states such as cataracts,
      differentiating the isomerization states is still not performed routinely. Here,
      we report the differentiation and semiquantitative analysis of an isoaspartic
      acid (betaAsp) in human alpha-Crystallin using postsource decay on a MALDI-TOF
      mass spectrometer incorporating a curved field reflectron. Our reproducible
      results of analyzing synthetic and tryptic peptides containing betaAsp
      corroborated results obtained using a previously reported diagnostic ion, y(l
      n+1) - 46, for the differentiation of betaAsp. The relative content of betaAsp in
      the peptide was successfully estimated from a unique ratio, y(l-n):y(l-n+1),
      corresponding to cleavages at the C- and N-termini, respectively, of the isomeric
      residues. The betaAsp content was consistent with measurements obtained
      independently by reversed phase HPLC analysis. Experiments in which neighboring
      amino acids adjacent to betaAsp/Asp were substituted revealed that the ratio
      between y(l-n) and y(l-n+1) reflected the isomerization status, while the
      diagnostic ion was observed only in the peptides that included an arginine
      residue at their C-terminus. Postsource decay experiments utilizing both the
      diagnostic ion and the characteristic fragment pattern could be applied to
      various kinds of peptides containing betaAsp.

PMID- 20669994
TI  - Comparative study of random and oriented antibody immobilization techniques on
      the binding capacity of immunosensor.
AB  - A comparative study of four different antibody immobilization techniques that are
      suitable for modification of surface plasmon resonance (SPR) chip (SPR-chip) is
      reported. Antibodies against human growth hormone (anti-HGH) were used as the
      model system. The evaluated SPR-chip modification techniques were (i) random
      immobilization of intact anti-HGH (intact-anti-HGH) via self-assembled monolayer
      (SAM) based on 11-mercaptoundecanoic acid (MUA); (ii) random immobilization of
      intact-anti-HGH within carboxymethyl dextran (CMD) hydrogel by direct covalent
      amine coupling technique; (iii) oriented coupling of intact-anti-HGH via Fc
      fragment to protein-G layer assembled on SAM consisting of MUA (MUA/pG); (iv)
      oriented immobilization of fragmented anti-HGH antibodies (frag-anti-HGH) via
      their native thiol-groups directly coupled to the gold. To liberate these thiol
      groups, the intact-anti-HGH was chemically "divided" into two frag-anti-HGH
      fragments by chemical reduction with 2-mercaptoethylamine (2-MEA). Optimal
      concentration of 2-MEA for preparation of anti-HGH was 15 mM. The surface
      concentration of immobilized antibodies and the antigen binding capacity for all
      four differently modified SPR-chips was evaluated and compared. The maximum
      surface concentration of immobilized intact-anti-HGH was obtained by immobilizing
      the antibody within CMD-hydrogel. The maximal antigen binding capacity was
      obtained by SPR-chip based on intact-anti-HGH immobilized via MUA/pG. The
      immobilization based on application of frag-anti-HGH was found to be the most
      suitable for design of SPR-immunosensor for HGH detection, due to its sufficient
      antigen binding capacity, simplicity, and low cost in respect to the currently
      evaluated techniques.

PMID- 20669995
TI  - Development of a quantitative metabolomic approach to study clinical human fecal
      water metabolome based on trimethylsilylation derivatization and GC/MS analysis.
AB  - Metabolomic analysis of human fecal water recently aroused increasing attention
      with the importance of fecal metabolome in exploring the relationships between
      symbiotic gut microflora and human health. In this study, we developed a
      quantitative metabolomic method for human fecal water based on
      trimethylsilylation derivatization and GC/MS analysis. Methanol was found to be
      the best solvent for protein precipitation and extraction of fecal water
      metabolome. Within the optimized linear range of sampling volume (less than 50
      microL), compounds showed a good linearity with a correlation coefficient higher
      than 0.99. The developed method showed good repeatability for both sample
      preparation and GC/MS analysis with the relative standard deviations lower than
      10% for most compounds and less than 20% for a few other ones. The method was
      further validated by studying analytical variability using a set of clinical
      samples as well as a pooled sample. The pH value and matrix effects were the main
      factors affecting the accuracy of quantitative calibration curves. The increased
      pH value decreased the loss of short chain fatty acids during lyophilization.
      Spiking fecal water to a standard mixture significantly enhanced the accuracy of
      quantitative calibration curves, probably due to the inhibition of volatile loss
      during lyophilization and the increase of compound solubility in the
      derivatization medium. A strategy for calibration curve preparation was proposed
      in order to avoid the effects of pH and matrix. Totally, 133 compounds were
      structurally confirmed from a set of clinical samples, and 33 of them were
      quantified, which demonstrates the suitability of this method for a quantitative
      metabolomic study of human fecal water samples.

PMID- 20669996
TI  - Characterization and improvement of signal drift associated with electron
      ionization quadrupole mass spectrometry.
AB  - Quadrupole mass spectrometry with electron ionization (EI-QMS) is a very popular
      detection technique in combination with gas chromatography. It is deployed for
      the analysis of volatile and semivolatile analytes in many industry domains.
      Although a very important factor for quantitative analysis, little is known about
      the stability of ion source performance. Only a few papers and patents report
      possible signal instabilities due to sample adsorption, degradation, or
      insulating deposits on the hot stainless steel surface of the ion source. In this
      study, a conventional stainless steel ion source was used to investigate possible
      signal drifts. It was observed that the EI-QMS instrument indeed suffered from
      continuous signal instability. It was found that the key parts which are
      responsible for the signal instabilities are those that regulate the ion beam
      toward the mass analyzer: the repeller, exit plate, and focusing lenses. The
      voltage of the repeller was found to have a major influence on the signal
      stability. The surface of the repeller, exit plate, and focusing lenses was
      modified by applying a gold coating. It was demonstrated that the signal
      stability of the MS dramatically improved when using the gold-coated parts. The
      contribution of each part to the stability improvement was quantitatively
      determined and compared with the standard stainless steel source performance. It
      was assumed that the signal drift observed with the stainless steel EI source
      originated from charge buildup on the surfaces. This hypothesis was supported by
      software simulations.

PMID- 20669997
TI  - Combinatorial libraries of synthetic peptides as a model for shotgun proteomics.
AB  - A synthetic approach to model the analytical complexity of biological proteolytic
      digests has been developed. Combinatorial peptide libraries ranging in length
      between 9 and 12 amino acids that represent typical tryptic digests were
      designed, synthesized, and analyzed. Individual libraries and mixtures thereof
      were studied by replicate liquid chromatography-ion trap mass spectrometry and
      compared to a tryptic digest of Deinococcus radiodurans. Similar to complex
      proteome analysis, replicate study of individual libraries identified additional
      unique peptides. Fewer novel sequences were revealed with each additional
      analysis in a manner similar to that observed for biological data. Our results
      demonstrate a bimodal distribution of peptides sorting to either very low or very
      high levels of detection. Upon mixing of libraries at equal abundance, a length
      dependent bias in favor of longer sequence identification was observed. Peptide
      identification as a function of site-specific amino acid content was
      characterized with certain amino acids proving to be of considerable importance.
      This report demonstrates that peptide libraries of defined character can serve as
      a reference for instrument characterization. Furthermore, they are uniquely
      suited to delineate the physical properties that influence identification of
      peptides, which provides a foundation for optimizing the study of samples with
      less defined heterogeneity.

PMID- 20669998
TI  - Evaluation of sampling and extraction methodologies for the global metabolic
      profiling of Saccharophagus degradans.
AB  - Metabolomics is based on the unbiased and global analysis of metabolites of
      organisms at specific time points. Therefore, the nonselective and reproducible
      recovery of all existing metabolites while preventing their transformation is the
      ideal criterion for metabolome sample preparation. We evaluated currently used
      sampling methods and extraction solvents for global metabolic profiling of a gram
      negative bacterium, Saccharophagus degradans, using gas chromatography-time-of
      flight mass spectrometry (GC-TOF MS) with an emphasis on three steps: the
      sampling method, which consisted of cold methanol quenching or fast filtration;
      the subsequent washing step; and the extraction solvents. After cold methanol
      quenching with 70% (v/v) methanol at -70 degrees C, washing with 2.3% NaCl
      produced a serious loss of intracellular metabolites. In addition, when cold
      methanol quenching and fast filtration were compared, severe cell leakage caused
      by cold methanol quenching resulted in a significant loss of intracellular
      metabolites, which was confirmed by spectrometric analysis at 260 and 280 nm.
      Upon evaluation of extraction solvents such as pure methanol (MeOH),
      acetonitrile/water (50ACN; 1:1, v/v), acetonitrile/methanol/water mixture (AMW;
      2:2:1), and water/isopropanol/methanol (WiPM; 2:2:5). AMW and WiPM were found to
      be superior extraction solvents for S. degradans based on the total peak
      intensities of the metabolites, the total number of metabolite peaks, and the
      reproducibility of recovered metabolite quantities; however, the metabolite
      profiles differed significantly between AMW and WiPM. This is the first
      evaluation of each step of sample preparation involved in global scale metabolic
      analysis by GC-TOF MS, which can be used as a model in the preparation of
      organism-specific samples for metabolome analysis.

PMID- 20669999
TI  - Laminar flow effects during laser-induced oxidative labeling for protein
      structural studies by mass spectrometry.
AB  - Laser-induced oxidative labeling of proteins provides insights into biomolecular
      structures and interactions. In these experiments, the hydroxyl radical ((*)OH)
      formed by photolysis of H(2)O(2) generates covalent modifications that are
      detectable by mass spectrometry. Under conditions where individual protein
      molecules are irradiated only once, the short (*)OH lifetime (approximately 1
      micros) ensures that covalent modifications are formed before any oxidation
      induced conformational changes take place. This feature implies that the method
      should be free of structural artifacts. It has been proposed that single-exposure
      conditions can be achieved by passing the solution through a capillary where
      successive laser pulses generate a string of irradiated flow segments that are
      well separated from one another. The current work explores the convection
      phenomena within the labeling capillary in more detail. The experiments are
      conducted at Reynolds numbers <<2000, resulting in laminar flow. The associated
      parabolic velocity profile causes a portion of each irradiated segment to remain
      in the labeling window during the subsequent laser pulse. Achieving a genuine
      single-exposure regime is, therefore, not possible. We estimate the fraction of
      labeled protein formed under laminar flow conditions, as well as the occurrence
      of multiple exposure events for any combination of experimental parameters (laser
      spot width, pulse frequency, and solution flow rate). A proper choice of these
      parameters provides extensive labeling, while keeping multiple exposure events at
      an acceptably low level. The theoretical framework developed here is supported by
      experimental data. Overall, this study reaffirms the feasibility of the use of
      flow devices for meaningful laser-induced oxidative labeling studies. At the same
      time, we provide a theoretical underpinning of this technique that goes beyond
      previously suggested plug flow models.

PMID- 20670000
TI  - Multilayer hybrid microfluidics: a digital-to-channel interface for sample
      processing and separations.
AB  - Microchannels can separate analytes faster with higher resolution, higher
      efficiency and with lower reagent consumption than typical column techniques.
      Unfortunately, an impediment in the path toward fully integrated microchannel
      based laboratories-on-a-chip is the integration of preseparation sample
      processing. In contrast, the alternative format of digital microfluidics (DMF),
      in which discrete droplets are manipulated on an array of electrodes, is well
      suited for carrying out sequential chemical reactions such as those commonly
      employed in proteomic sample preparation. We recently reported a new paradigm of
      "hybrid microfluidics," integrating DMF with microchannels for in-line sample
      processing and separations. Here, we build on our initial efforts, introducing a
      second-generation hybrid microfluidic device architecture. In the new multilayer
      design, droplets are manipulated by DMF in the two-plate format, an improvement
      that facilitates dispensing samples from reservoirs, as well as droplet splitting
      and storage for subsequent analysis. To demonstrate the capabilities of the new
      method, we implemented an on-chip serial dilution experiment, as well as
      multistep enzymatic digestion. Given the myriad applications requiring
      preprocessing and chemical separations, the hybrid digital-channel format has the
      potential to become a powerful new tool for micro total analysis systems.

PMID- 20670001
TI  - Enyne [4 + 4] photocycloaddition: bridged 1,2,5-cyclooctatrienes.
AB  - Enyne photocycloaddition with a 2-pyridone yields a mixture of products including
      amide-bridged 1,2,5-cyclooctatrienes, the first examples of enyne [4 + 4]
      adducts. Four regio- and stereochemical isomers of the [4 + 4] adduct are
      possible. All appear to be too strained to be isolated, but they have been
      identified as their [2 + 2] cyclobutane dimers. Cyclobutane and cyclobutene
      adducts have also been isolated, [2 + 2] addition products possibly related to
      the unstable [4 + 4] adducts via Cope rearrangement. Calculations suggest that
      [3,3] rearrangements have high energy barriers, however, making thermal
      interconversion unlikely.

PMID- 20670002
TI  - Cationic Pd(II)-catalyzed tandem reaction of 2-arylethynylanilines and aldehydes:
      an efficient synthesis of substituted 3-hydroxymethyl indoles.
AB  - An efficient cationic palladium(II)-catalyzed synthesis of substituted 3
      hydroxymethylindoles from readily accessible starting materials is developed.
      This tandem reaction involves an intramolecular aminopalladation of an alkyne and
      an addition to the carbonyl group to quench the carbon-palladium bond to complete
      the catalytic cycle without the necessity of a redox system.

PMID- 20670003
TI  - Stereoselective synthesis of the C1-C11 and C12-C34 fragments of mycalolide A.
AB  - A convergent synthesis of the C1-C11 and C12-C34 fragments of mycalolide A is
      described. Synthetic highlights include a highly E-selective cross-metathesis
      between a vinyl-functionalized bis-oxazole unit and a polypropionate side chain
      to introduce the C19-C20 double bond and an enzymatic desymmetrization of a meso
      diol in addition to five stereoselective allylations/crotylations to control the
      11 stereogenic centers present in the natural product.

PMID- 20670004
TI  - A stable heptacene derivative substituted with electron-deficient
      trifluoromethylphenyl and triisopropylsilylethynyl groups.
AB  - A heptacene derivative 1 substituted with four electron-deficient
      trifluoromethylphenyl and two triisopropylsilylethynyl (TIPSE) groups was
      prepared by a new synthetic strategy. Photo-oxidative resistance studies showed
      that this newly developed heptacene compound persisted 47 h in solution under
      ambient light and air conditions, and it represents the most stable heptacene
      derivative reported to date.

PMID- 20670005
TI  - Asymmetric hydrogenation of bicyclic ketones catalyzed by BINAP/IPHAN-Ru(II)
      complex.
AB  - Hydrogenation of 3-quinuclidinone and bicyclo[2.2.2]octan-2-one with a combined
      catalyst system of RuCl(2)[(S)-binap][(R)-iphan] and t-C(4)H(9)OK in 2-propanol
      afforded the chiral alcohols in 97-98% ee. 2-Diphenylmethyl-3-quinuclidinone was
      hydrogenated with the same catalyst to the cis alcohol with perfect diastereo-
      and enantioselectivity. The reaction of unsymmetrical ketones with a
      bicyclo[2.2.1] or -[2.2.2] skeleton gave the corresponding alcohols with high
      stereoselectivity.

PMID- 20670006
TI  - Alchivemycin A, a bioactive polycyclic polyketide with an unprecedented skeleton
      from Streptomyces sp.
AB  - Alchivemycin A, a novel polycyclic polyketide, was isolated from the culture
      extract of a plant-derived actinomycete Streptomyces sp. The structure and
      relative configuration were elucidated by spectroscopic analysis and X-ray
      crystallography, and the absolute configuration was determined by a (1)H NMR
      anisotropy method using MPA ester derivatization. The new compound contains an
      unprecedented heterocyclic ring system, 2H-tetrahydro-4,6-dioxo-1,2-oxazine.
      Alchivemycin A showed potent antimicrobial activity against Micrococcus luteus
      and inhibitory effects on tumor cell invasion.

PMID- 20670007
TI  - Target-directed synthesis of antibacterial drug candidate GSK966587.
AB  - An efficient enantioselective total synthesis of the potent antibiotic GSK966587
      was accomplished. Highlights of the synthesis include two innovative Heck
      reactions, a highly selective zincate base directed ortho-metalation, Sharpless
      asymmetric epoxidation, and a fully convergent final step fragment coupling.

PMID- 20670008
TI  - Synthesis of fluoroazaindolines by an uncommon radical ipso substitution of a
      carbon-fluorine bond.
AB  - Rare examples of a synthetically useful radical ipso substitution of a carbon
      fluorine bond are reported. Highly functionalized fluoroazaindoline structures
      have thus been prepared with use of cheap and readily available substrates and
      reagents.

PMID- 20670009
TI  - Titanium-mediated spirocyclization reactions of 4-alkylpyridines.
AB  - Pyridines substituted at the 4-position with alkyl tethers containing beta
      dicarbonyl moieties were converted to spirocyclic 4,4-disubstituted
      dihydropyridines. Optimal conditions for these transformations involved N
      acylation of the pyridine substrate with a chloroformate electrophile in the
      presence of Ti(O(i)Pr)(4). Cyclization products could be easily converted into
      spiro-piperidine derivatives or elaborated into more complex heterocyclic
      frameworks via Au-catalyzed cycloisomerization.

PMID- 20670010
TI  - Synthesis of small and large fused bicyclic compounds by tandem dienyne ring
      closing metathesis.
AB  - A tandem ring-closing metathesis reaction using ruthenium catalyst was carried
      out to synthesize various fused bicyclic compounds containing both small and
      large rings. Fast ring-closure of the small ring and slow ring-closure of the
      large ring resulted in the formation of only one isomer. Further manipulation
      such as the Diels-Alder reaction was carried out to prepare a complex molecule
      containing multiple rings of different sizes.

PMID- 20670011
TI  - First C-H activation route to oxindoles using copper catalysis.
AB  - The preparation of 3,3-disubstituted oxindoles by a formal C-H, Ar-H coupling of
      anilides is described. Highly efficient conditions have been identified using
      catalytic (5 mol %) Cu(OAc)(2).H(2)O with atmospheric oxygen as the reoxidant; no
      additional base is required, and the reaction can be run in toluene or
      mesitylene. Optimization studies are reported together with a scope and
      limitation investigation based on variation of the anilide precursors. The
      application of this methodology to prepare a key intermediate for the total
      synthesis of the anticancer, analgesic oxindole alkaloid Horsfiline is also
      described.

PMID- 20670012
TI  - Decarboxylative acylation of arenes with alpha-oxocarboxylic acids via palladium
      catalyzed C-H activation.
AB  - An efficient palladium-catalyzed decarboxylative acylation of unactivated arenes
      with alpha-oxocarboxylic acids is reported. This method provides a novel access
      to aryl ketones.

PMID- 20670013
TI  - Facile dimer synthesis for DNA-binding polyamide ligands.
AB  - Pyrrole-imidazole polyamide ligands are highly sequence specific synthetic DNA
      binding ligands that bind with high affinity. To counter the synthetic
      difficulties associated with coupling the electron-rich heterocyclic acids to the
      electron-deficient nucleophilic imidazole amine, a novel approach is described
      for synthesis of Fmoc-protected dimers for solid-phase peptide synthesis (SPPS).
      This method produces the dimers in high yields, is broadly applicable to other
      heterocyclic-containing polyamides, and results in improved ligand yields and
      synthesis times.

PMID- 20670014
TI  - Straightforward synthesis of enantiopure 2,3-dihydrobenzofurans by a sequential
      stereoselective biotransformation and chemical intramolecular cyclization.
AB  - A new family of optically active 2,3-dihydrobenzofurans has been prepared by a
      simple chemoenzymatic asymmetric strategy. This synthetic approach is based on
      the combination of a lipase-mediated kinetic resolution of 1-aryl-2-propanols or
      bioreduction of the corresponding ketones followed by an intramolecular
      cyclization reaction. These novel compounds have been prepared in enantiopure
      form and in good overall yield through a straightforward route.

PMID- 20670015
TI  - Fast isomerizing methyl iodide azopyridinium salts for molecular switches.
AB  - The usefulness of azopyridinium methyl iodide salts for designing new promising
      light-controlled molecular switches is presented. Large absorbance changes have
      been produced in the samples by irradiation with light at lambda = 355 nm. The
      thermal recovery of the initial state took place completely within 130-450 ms,
      which is much faster than that reported previously for other push-pull azobenzene
      doped nematic mixtures.

PMID- 20670016
TI  - Efficient synthesis of a peculiar vicinal diamine semiochemical from Streptomyces
      natalensis.
AB  - The pimaricin-inducing (PI) factor, produced by Streptomyces natalensis is a
      proposed pheromone with a peculiar vicinal diamine structure. The first synthesis
      of this molecule is reported. It features oxidative dimerization of an aci-nitro
      anion derived from tris(hydroxymethyl)nitromethane and disproportionation
      catalyst-facilitated hydrogenation of the resulting vicinal tertiary dinitro
      compound. As the synthesis requires only four steps with no chromatographic
      separations, it provides a convenient route to prepare PI factor for biological
      studies and industrial applications.

PMID- 20670017
TI  - Stereocontrolled synthesis of 2-substituted-1,3-azasilaheterocycles.
AB  - Chiral alpha-silylsulfinamides, prepared by the treatment of an
      alkyldiphenylsilane with lithium followed by its addition to a sulfinimine, can
      be applied to the synthesis of 1,3-azasilaheterocycles as derivatives of cyclic
      alkaloids. This synthetic route, which involves intramolecular substitution of an
      amino alcohol or cyclization of an amino acid promoted by 1-ethyl-3-(3
      dimethylaminopropyl)carbodiimide (EDC), represents a convenient means for
      accessing these silicon-containing heterocycles.

PMID- 20670018
TI  - Synthetic access to bent polycycles by cation-pi cyclization.
AB  - The presence of an ether oxygen within a chain undergoing cation-polyene
      cyclization has a profound influence on the stereochemistry of this important
      construction, apparently due to nucleophilic participation of oxygen in the
      cyclization process and formation of an oxonium intermediate, leading to bent
      fused ring systems.

PMID- 20670019
TI  - Synthesis of novel thermally reversible photochromic axially chiral
      spirooxazines.
AB  - The Suzuki reactions of diboronic acid 1 and bromo-spirooxazine 2, under N(2)
      atmosphere and aerobic conditions, gave the dispirooxazine-substituted binaphthyl
      product 3 and the monospirooxazine-substituted binaphthyl derivative 4,
      respectively. The thermally reversible photochromic behavior of the target
      axially chiral spirooxazines 3 was investigated, and both the ring-opening
      process upon irradiation with 365 nm light and the thermally reverse ring-closing
      process were fast. These chiral spirooxazines were found to impart their
      chirality to an achiral liquid crystal host, at low doping levels, to form a self
      organized photoresponsive helical superstructure.

PMID- 20670020
TI  - Stereoselective synthesis of 1,2,3,4-tetrasubstituted dienes from allenoates and
      aldehydes: an observation of phosphine-induced chemoselectivity.
AB  - Phosphine-mediated olefination between alpha-substituted allenoates and aldehydes
      to form 1,2,3,4-tetrasubstituted 1,3-dienes is presented. High levels of chemo-
      and diastereoselectivity and yield are obtained for a wide scope of substrates
      with the choice of appropriate phosphines. This reaction evidences the capacity
      of phosphines in the control of reaction pathways and provides a highly efficient
      synthetic method for tetrasubstituted conjugated dienes.

PMID- 20670021
TI  - Carbon dioxide as the C1 source for direct C-H functionalization of aromatic
      heterocycles.
AB  - A simple and straightforward method has been developed for the direct
      carboxylation of aromatic heterocycles such as oxazoles, thiazoles, and
      oxadiazoles using CO(2) as the C1 source. The reactions require no metal catalyst
      and only Cs(2)CO(3) as the base. A good functional group tolerance is achieved.

PMID- 20670023
TI  - Does 2-methylacetophenone comply with steric inhibition of resonance? A direct
      experimental proof of its nonplanar conformation from a joint ab initio/electron
      diffraction analysis.
AB  - The structure and conformations of 2-methylacetophenone (1) have been
      investigated by ab initio calculations carried out at the MP2(full)/6-311++G**
      level and by gas electron diffraction (GED). According to both methods, 1 exists
      predominantly as a form with the C=O bond synclinal with respect to the C(ar)
      C(O) bond (1B), with a torsional angle [C(6)-C(1)-C=O] of 32.7(24) degrees as
      determined by GED and 26.0 degrees from MP2(full)/6-311++G**. Calculations also
      predict the presence of a second conformer, the anticlinal structure (1C), with
      phi = 140.0 degrees, with an abundance of less than 6%, an amount hardly
      detectable by GED. Different DFT computational protocols both support a nonplanar
      form of the predominant conformer (B2PLYP) and are in contradiction (B3LYP,
      M052x, B98, B97-D) with this experimental finding. The GED results, supported by
      the calculations that involve long-range correlation, are in a good agreement
      with (13)C NMR spectroscopic investigations, UV spectra, and dipole moment
      studies. However, previous claims that assumed steric inhibition of resonance
      caused by a significantly nonplanar conformation with phi close to 90 degrees
      have been disproved. Steric crowding is evident from the geometrical parameters,
      particularly from the C(1)-C(2) bond length and from the C(1)-C(2)-C(H(3)) and
      C(2)-C(1)-C(O) bond angles. It is concluded that any explanation of reactivity by
      steric inhibition of resonance and by other steric factors must be supported by
      experimental and/or theoretical investigation of the actual molecular shape.

PMID- 20670024
TI  - Nucleophilicity and site selectivity of commonly used arenes and heteroarenes.
AB  - By using the inverse concept of electrophilicity and nucleophilicity and with
      four different available equations from literature for electrophilicity and
      electrodonating power, the nucleophilicity values of 69 commonly used arenes and
      heteroarenes have been calculated at the B3LYP/6-311+G(d,p) level of theory. The
      linearity between the nucleophilicity and Hammett sigma and sigma(p) values has
      been chosen as a test to judge the goodness of the methods used. Finally four
      different arene and heteroarene series (substituted indoles, phenols, pyrroles,
      and anisoles) have been subjected to local nucleophilicity analysis in order to
      predict the site selectivity in electrophilic aromatic substitution reactions
      (EAS). In each case we have obtained excellent correlation with the experimental
      result.

PMID- 20670025
TI  - Probing the effect of acylation on arabinofuranose ring conformation in di- and
      trisaccharide fragments of mycobacterial arabinogalactan.
AB  - A major component of the cell wall of mycobacteria is the mycolyl-arabinogalactan
      (mAG) complex. The arabinose and galactose residues in mAG are found solely in
      the furanose form, and it has been suggested that the flexibility of these five
      membered rings allows for the tight packing of mycolic acids. In order to probe
      the "flexible scaffold hypothesis", we designed and synthesized glycolipids 3-6
      and 8-11 as simple models of the terminal portion of mAG. A set of donors and
      acceptors were explored for preparing the key beta-(1-->2) linkage in 2-6, and
      the best selectivity and yield can be obtained by using the electron-rich
      thioglycoside donor 14 and the O-5 p-methoxybenzyl-protected acceptor 17. Both
      alpha-linkages in the trisaccharides 7-11 were formed in a one-pot reaction. The
      conformations of compounds 2-11 were studied using solution-state NMR
      spectroscopy, but little change was observed in the coupling constants for the
      ring protons between 2 and 3-6 or between 7 and 8-11. However, the rotamer
      populations about the C-4-C-5 bond for the beta-linked ring in disaccharide 2 did
      change upon acylation at O-5.

PMID- 20670026
TI  - Successful computational modeling of isobornyl chloride ion-pair mechanisms.
AB  - Along with the directly related Wagner-Meerwein camphene hydrochloride-isobornyl
      chloride rearrangement, the racemization of isobornyl chloride involves
      intermediate carbocation-anion ion pairs; both processes have become mechanistic
      icons in organic chemistry. The two known racemization pathways, involving either
      a hydride transfer or a methyl migration, are observed to be concurrent. However,
      prior quantitative computational modeling has not been able to reproduce the fine
      kinetic balance of these processes. We demonstrate that a density functional
      approach, which includes two explicit solvent molecules embedded in a continuum
      solvent field, coupled with full geometric optimization using smoothed solvent
      cavities and free energy calculation, yields results in accord with experiment.
      Alternative racemization routes also have been explored.

PMID- 20670027
TI  - Total synthesis of depsilairdin.
AB  - The total synthesis of depsilairdin, a host-selective phytotoxin isolated from
      Leptosphaeria maculans (the causal agent of blackleg disease of oilseed
      Brassicas), has been achieved by N-terminal extension of a suitably protected
      derivative of the hitherto unknown amino acid (2S,3S,4R)-3,4-dihydroxy-3-methyl
      proline (Dhmp) followed by esterification with lairdinol A. The latter
      esterification, complicated by the sterically hindered nature of the carboxyl
      group, was accomplished by a novel method involving reaction of the 1
      hydroxybenzotriazole (HOBt) derived active ester with the bromomagnesium alkoxide
      of lairdinol A. Three depsilairdin analogues were also prepared by replacing the
      Dhmp residue with L-proline and cis- and trans-4-hydroxy-L-proline. Phytotoxicity
      assays showed that the analogues were nontoxic to both blackleg-susceptible
      (brown mustard) and -resistant (canola) plants, suggesting that the presence of
      the Dhmp residue in depsilairdin is important for its host-selective toxicity
      toward brown mustard.

PMID- 20670028
TI  - 4-Bis(methylthio)methylene-2-phenyloxazol-5-one: versatile template for synthesis
      of 2-phenyl-4,5-functionalized oxazoles.
AB  - 4-Bis(methylthio)methylene-2-phenyloxazol-5-one has been shown to be a versatile
      template for the synthesis of various 2-phenyl-3,4-substituted oxazoles via
      nucleophilic ring-opening of oxazolone with various oxygen, nitrogen, and carbon
      nucleophiles and subsequent 5-endo cyclization of the resulting acyclic adducts
      in the presence of silver carbonate.

PMID- 20670029
TI  - Lewis acid promoted reactions of ethenetricarboxylates with allenes: synthesis of
      indenes and gamma-lactones via conjugate addition/cyclization reaction.
AB  - Indenes are important core structures in organic chemistry. Few simple
      arylallenes have been used to construct indene skeletons by Friedel-Crafts
      reaction. Lewis acid catalyzed reaction of ethenetricarboxylates 1 and
      arylallenes has been examined in this study. The reaction of arylallenes and
      ethenetricarboxylate triesters with SnCl(4) gave indene derivatives efficiently,
      via a conjugate addition/Friedel-Crafts cyclization reaction. On the other hand,
      the reactions of 1,1-diethyl 2-hydrogen ethenetricarboxylate and arylallenes or
      alkylallenes with SnCl(4) at -78 degrees C or room temperature and subsequent
      treatment with Et(3)N gave gamma-lactones. The reactions of triethyl
      ethenetricarboxylate and 1,1-dialkylallenes with SnCl(4) at room temperature also
      gave gamma-lactones.

PMID- 20670030
TI  - Three-dimensional structural control of diastereomeric Leu-Leu-Aib-Leu-Leu-Aib
      sequences in the solid state.
AB  - Three diastereomeric -Leu-Leu-Aib-Leu-Leu-Aib- peptides composed of the same
      numbers of L-Leu, D-Leu, and Aib residues were synthesized: Boc-L-Leu-L-Leu-Aib-D
      Leu-D-Leu-Aib-OMe (1), Boc-L-Leu-D-Leu-Aib-L-Leu-D-Leu-Aib-OMe (2), and Boc-L-Leu
      D-Leu-Aib-D-Leu-L-Leu-Aib-OMe (3). The crystals of the three peptides were
      characterized by X-ray crystallographic analysis as follows: (1) orthorhombic,
      P2(1)2(1)2(1), a = 21.383 A, b = 11.070 A, c = 19.560 A, Z = 4, R(1) = 0.0527,
      and R(w) = 0.1562; (2) monoclinic, P2(1), a = 9.391 A, b = 21.278 A, c = 11.662
      A, beta = 99.125, Z = 2, R(1) = 0.0507, and R(w) = 0.1447; and (3) triclinic, P1,
      a = 12.545 A, b = 14.913 A, c = 15.330 A, alpha = 77.622, beta = 66.601, gamma =
      78.839, Z = 2, R(1) = 0.0775, and R(w) = 0.1971. The three diastereomeric
      peptides, 1, 2, and 3, showed unique conformations. That is to say, 1 was folded
      into a left-handed (M) 3(10)-helical structure, 2 was folded into a distorted
      beta-hairpin nucleated by a type II' beta-turn-like structure, and 3 was folded
      into an S-shape turn structure based on two type II/III beta-turns.

PMID- 20670031
TI  - Nucleophilic reactivities of imide and amide anions.
AB  - The kinetics of the reactions of amide and imide anions 2a-o with benzhydrylium
      ions 1a-i and structurally related quinone methides 1j-q have been studied by UV
      vis spectroscopy in DMSO and acetonitrile solution. The second-order rate
      constants (log k(2)) correlated linearly with the electrophilicity parameters E
      of 1a-q according to the correlation log k(2) = s(N + E) (Angew. Chem., Int. Ed.
      Engl. 1994, 33, 938-957), allowing us to determine the nucleophilicity parameters
      N and the nucleophile-specific parameters s for these nucleophiles. The
      reactivities of all sulfonamide and diacylimide anions are found in a relatively
      small range (15 < N < 22). Comparison with structurally related carbanions
      revealed that amide and imide anions are less reactive than carbanions of the
      same pK(aH). These effects can be attributed to the absence of resonance
      stabilization of one of the lone pairs in the amide or imide anions. As amide and
      imide anions are exclusively attacked at nitrogen by benzhydrylium ions,
      Kornblum's interpretation of the ambident reactivity of amide anions has to be
      revised.

PMID- 20670032
TI  - An investigation of wall effects in microwave-assisted ring-closing metathesis
      and cyclotrimerization reactions.
AB  - Challenging Ru-catalyzed ring-closing metathesis transformations leading to eight
      membered-ring systems and Ni- or Co-catalyzed [2+2+2] cyclotrimerizations were
      evaluated at elevated temperatures applying microwave dielectric heating or
      conventional thermal heating in order to investigate the role of wall effects.
      All reactions were conducted in a dedicated reactor setup that allowed accurate
      internal reaction temperature measurements using fiber-optic probes for both
      types of heating modes. For ring-closing metathesis best results were achieved
      using an open vessel-gas sparging protocol in 1,2-dichloroethane at reflux
      temperature (83 degrees C), while cyclotrimerizations were performed under sealed
      vessel conditions in toluene between 80 and 160 degrees C. For all studied
      transformations the results achieved in a single-mode microwave reactor could be
      reproduced by conventional heating in an oil bath by carefully matching the
      temperature profiles as close as possible during the entire heating and cooling
      cycle. In contrast to previous literature reports, no evidence that direct in
      core microwave heating can increase catalyst lifetime by minimization or
      elimination of wall effects was obtained. At the same time, no indication for the
      involvement of nonthermal microwave effects in these homogeneous transition metal
      catalyzed transformations was seen.

PMID- 20670033
TI  - One-pot synthesis of aminoenone via direct reaction of the chloroalkyl enone with
      NaN3: rapid access to polycyclic alkaloids.
AB  - A new one-pot procedure for the preparation of aminoenone from chloroalkyl enone
      and sodium azide was demonstrated. The structure of the presumed triazoline
      intermediate in this process was confirmed by X-ray analysis for the first time.
      As the application of this methodology, the synthesis of polycyclic alkaloid
      hexahydroapoerysopine (1a) was achieved through an efficient synthetic route.

PMID- 20670034
TI  - Characterization of the 4-(benzothiazol-2-yl)phenylnitrenium ion from a putative
      metabolite of a model antitumor drug.
AB  - The 4-(benzothiazol-2-yl)phenylnitrenium ion 11 is generated from hydrolysis or
      photolysis of O-acetoxy-N-(4-(benzothiazol-2-yl)phenyl)hydroxylamine 8, a model
      metabolite of 2-(4-aminophenyl)benzothiazole 1 and its ring-substituted
      derivatives that are being developed for a variety of medicinal applications,
      including antitumor, antibacterial, antifungal, and imaging agents. Previously,
      we showed that 11 had an aqueous solution lifetime of 530 ns, similar to the 560
      ns lifetime of the 4-biphenylylnitrenium ion 12 derived from the well-known
      chemical carcinogen 4-aminobiphenyl. We now show that the analogy between these
      two cations extends well beyond their lifetimes. The initial product of hydration
      of 11 is the quinolimine 16, which can be detected as a long-lived reactive
      intermediate that hydrolyzes in a pH-dependent manner into the final hydrolysis
      product, the quinol 15. This hydrolysis behavior is equivalent to that previously
      described for a large number of ester metabolites of carcinogenic arylamines,
      including 4-aminobiphenyl. The major azide trapping product (90% of azide
      products) of 11, 20, is generated by substitution on the carbons ortho to the
      nitrenium ion center of 11. This product is a direct analogue of the major azide
      adducts, such as 22, generated from trapping of the nitrenium ions of
      carcinogenic arylamines. The azide/solvent selectivity for 11, k(az)/k(s), is
      also nearly equivalent to that of 12. A minor product of the reaction of 11 with
      N(3)(-), 21, contains no azide functionality but may be generated by a process in
      which N(3)(-) attacks 11 at the nitrenium ion center with loss of N(2) to
      generate a diazene 25 that subsequently decomposes into 21 with loss of another
      N(2). The adduct derived from attack of 2'-deoxyguanosine (d-G) on 11, 28, is a
      familiar C-8 adduct of the type generated from the reaction of d-G with a wide
      variety of arylnitrenium ions derived from carcinogenic arylamines. The rate
      constant for reaction of d-G with 11, k(d-G), is very similar to that observed
      for the reaction of d-G with 12. The similar lifetimes and chemical reactivities
      of 11 and 12 can be rationalized by B3LYP/6-31G(d) calculations on the two ions
      that show that they are of nearly equivalent stability relative to their
      respective hydration products. The calculations also help to rationalize the
      different regiochemistry observed for the reaction of N(3)(-) with 11 and its
      oxenium ion analogue, 13. Since 8 is the likely active metabolite of 1 and a
      significant number of derivatives of 1 are being developed as pharmaceutical
      agents, the similarity of the chemistry of 11 to that of carcinogenic
      arylnitrenium ions is of considerable importance. Consideration should be given
      to this chemistry in continued development of pharmaceuticals containing the 2-(4
      aminophenyl)benzothiazole moiety.

PMID- 20670035
TI  - A safe and practical procedure for global deprotection of oligoribonucleotides.
AB  - We report a practical global deprotection of RNA 2'-O-tert-butyldimethylsilyl
      (TBS) ethers using commercially available aqueous NH(4)F. The procedure is
      applicable to both 96-well plate format and large-scale production of RNA. This
      improved procedure provides a safe, mild, and cost-effective alternative to
      highly hazardous Et(3)N x 3 HF, a reagent commonly used in the routine synthesis
      of RNA.

PMID- 20670036
TI  - Boron-containing monopyrrolo-annelated tetra thiafulvalene compounds: synthesis
      and absorption spectral/electrochemical responsiveness toward fluoride ion.
AB  - Two new boron-based conjugated compounds 1 and 2 containing one and three
      monopyrrolo-annelated tetrathiafulvalene (TTF) unit(s) were synthesized and
      characterized. They exhibit typical ICT absorptions which can be modulated after
      addition of fluoride ion. In addition, the oxidation potentials of 1 and 2 are
      shifted to low potential region in the presence of fluoride ion. Such absorption
      spectral and electrochemical responsiveness of 1 and 2 toward fluoride ion is due
      to the binding of the boron units with fluoride ion.

PMID- 20670037
TI  - Synthesis of the sulfonate analogue of seminolipid via Horner-Wadsworth-Emmons
      olefination.
AB  - The first synthesis of the sulfonate analogue of seminolipid, the main
      sulfoglycolipid in mammalian sperm, is reported. Installation of the sulfonate
      unit was accomplished by a quite unexplored strategy based on Horner-Wadsworth
      Emmons olefination on a 3 '-keto-galactoside, followed by stereoselective double
      bond reduction.

PMID- 20670038
TI  - Rearrangement of 2,3-epoxy alcohol dimethylthiocarbamate derivatives. Synthesis
      of 2,3-epithio alcohol derivatives under mild conditions.
AB  - Transformation of representative 2,3-epoxy alcohols, including 3-trimethylsilyl-
      and 3-triphenylsilylglycidols, into the corresponding 2,3-epithio alcohol
      dimethylthiocarbamate derivatives under mild alkaline conditions is reported.

PMID- 20670039
TI  - Biomimetic total synthesis of (+)-chabranol.
AB  - A concise, biomimetic total synthesis of the unprecedented terpenoid skeleton (+)
      chabraol has been accomplished via 6 steps from the chiral epoxide 7, involving
      an intramolecular Prins double cyclization to yield the bicyclo[2.2.1] core of
      the natural product as the key step. The absolute configuration of natural
      chabranol was also designated through the first asymmetric total synthesis.

PMID- 20670040
TI  - An intermolecular hydroamination of allenamides with arylamines catalyzed by
      cationic Au(I) salts.
AB  - An intermolecular hydroamination of allenamides with arylamines has been achieved
      under mild Au(I) catalysis conditions delivering allylamino E-enamides
      stereoselectively and in high yield. The reaction is made possible via a
      convenient method for conjugated N-acyliminium formation.

PMID- 20670041
TI  - Bronsted acid-mediated Nazarov cyclization of vinylallenes.
AB  - Treatment of siloxy enynes with base leads to the corresponding
      vinylsiloxyallenes which undergo Nazarov cyclization in the presence of
      trifluoroacetic acid to provide the cyclized product as a mixture of regioisomers
      in moderate to good overall yield.

PMID- 20670042
TI  - Palladium-catalyzed direct oxidative alkenylation of azoles.
AB  - The direct heteroaromatic sp(2) C-H alkenylation of 2-substituted azole compounds
      with alkenes proceeds in the presence of Pd(OAc)(2) and AgOAc as catalyst and
      oxidant, respectively, to afford the corresponding 5-alkenylated azoles in good
      yields.

PMID- 20670043
TI  - Management of chronic pain. Foreword.

PMID- 20670044
TI  - Oxycodone/paracetamol: a low-dose synergic combination useful in different types
      of pain.
AB  - The combination of two analgesic agents offers several advantages in the
      treatment of chronic pain. Paracetamol (acetaminophen) has central analgesic
      activity without a nonsteroidal anti-inflammatory drug (NSAID)-like or opioid
      like effect. Oxycodone is a semisynthetic opioid agonist. The oral fixed-dose
      combination of oxycodone and paracetamol immediate-release formulation has a
      synergistic mechanism of action that is useful for moderate-to-severe pain and
      for nonresponders to NSAIDs or paracetamol alone. This fixed-dose combination
      offers several advantages: lower individual drug doses can be used because of
      their synergistic mechanisms of action, its opioid-sparing effect and it has a
      good efficacy and tolerability profile. Efficacy and safety of this fixed-dose
      combination were assessed in a wide range of clinical settings: in patients with
      osteoarthritis or chronic musculoskeletal pain, including when complicated by a
      neuropathic component; for chronic pain in elderly patients; cancer-related pain;
      postoperative pain; and for neuropathic pain, in the latter case usually given in
      combination with an NSAID or other drugs. The large variety of indications for
      which this fixed-dose combination may be useful can be attributed to the
      pharmacological synergy between oxycodone and paracetamol and because lower
      individual drug dosages can be used, suggesting that this should be a first-line
      agent for the treatment of chronic moderate-to-severe pain.

PMID- 20670045
TI  - Pre-emptive analgesia for postoperative pain control: a review.
AB  - Pain can play an important role at the social and psychological level; hence one
      of the major goals of anaesthesia is to control and reduce the incidence of
      postoperative pain. The use of an analgesia before surgical incision may offer
      one of the most innovative and promising strategies for better pain control
      throughout the perioperative period. Pre-emptive analgesia refers to
      pharmacological intervention initiated prior to a painful stimulus in order to
      inhibit nociceptive mechanisms before they are triggered. Pre-emptive analgesia
      has three objectives: to reduce pain resulting from the activation of
      inflammatory mechanisms triggered by surgical incision; to hinder the pain memory
      response of the central nervous system; and to ensure a good control of
      postoperative pain in order to avoid the development of chronic pain. The
      following provides an overview of the scientific rationale for pre-emptive
      analgesia alongside an overview of published systematic reviews and randomized
      clinical trials related to this topic.

PMID- 20670046
TI  - Idiopathic breakthrough pain: a new hypothesis.
AB  - Breakthrough pain (BTP) in treated patients with chronic pain states is neither
      well defined nor well understood. BTP is generally defined as a transient
      exacerbation of pain experienced by a patient with relatively stable and
      adequately controlled baseline pain. It is usually categorized as spontaneous,
      with no known cause, or incident, when initiated by voluntary or involuntary
      movements, or therapeutic procedures. Since pain is related to survival, it
      possibly cannot be completely and permanently controlled. It is hypothesized that
      glia are at least partially responsible for inducing pain spikes by attempting to
      reactivate unresponsive neurons. Therefore, compounds that modulate microglia may
      offer potential alternative therapeutic options in the control of idiopathic BTP.

PMID- 20670047
TI  - Transdermal buprenorphine in non-oncological moderate-to-severe chronic pain.
AB  - BACKGROUND: Musculoskeletal pathologies are among the most frequent causes of
      long-term non-oncological severe pain and consequent physical impairment. Aims of
      pharmacological and physical therapy are to reduce pain, promote functional
      recovery and improve overall quality of life. Pharmacological therapy may include
      the use of opioids. OBJECTIVE: To evaluate the efficacy and tolerability of
      transdermal buprenorphine (TDS) in the long-term management of non-oncological,
      chronic, moderate-to-severe musculoskeletal pain. STUDY DESIGN: An open-label,
      prospective, single-centre, 6-month study. SETTING: A 'real world' outpatient
      setting. PATIENTS: Adult patients with chronic moderate-to-severe musculoskeletal
      pain were enrolled consecutively. INTERVENTION: Patients initially received
      buprenorphine TDS 11.7 microg/h (one-third of 35 microg/h patch) every 72 hours.
      If required, patients could be up-titrated to 17.5 microg/h (one-half of 35
      microg/h patch), 23.4 microg/h (two-thirds of 35 microg/h patch) or 35 microg/h.
      Concomitant antiemetics were allowed. MAIN OUTCOME MEASURES: The primary endpoint
      was percentage mean reduction in static and dynamic pain visual analogue scale
      (VAS) scores at study end (10 being worst pain, 0 being no pain). Quality of life
      and tolerability were also assessed. RESULTS: We enrolled 146 patients aged 41-94
      years; their baseline mean +/- SD static and dynamic pain VAS scores were 6.87 +/
      1.89 and 7.70 +/- 1.74, respectively. Buprenorphine TDS initial dosages were
      11.7 microg/h (n = 139), 17.5 microg/h (n = 4), 23.4 microg/h (n = 1) and 35
      microg/h (n = 2). At 6 months, 89 patients were under treatment; 11% (n = 10)
      were receiving 11.7 microg/h, 30% (n = 27) 17.5 microg/h, 6% (n = 5) 23.4
      microg/h and 53% (n = 47) 35 microg/h. Patients achieved a nonsignificant
      reduction in pain at rest and in movement; mean +/- SD static and dynamic pain
      VAS scores decreased to 1.56 +/- 2.05 and 3.54 +/- 2.02, respectively. The
      quality of life improved as shown by significant (p < 0.01) increases from
      baseline in all items relating to physical and mental health on the Short-Form 36
      health survey. Patients experienced recovery of daily and social activities
      according to the significant (p < 0.01) increase in Karnofsky Performance Status
      sub-item scores. Twenty-three patients discontinued treatment because of adverse
      events, which were mainly gastrointestinal or CNS-related. CONCLUSIONS: Low-dose
      buprenorphine TDS had good analgesic efficacy, and quality of life improved as
      early as 1 month after treatment initiation. Our results suggest that
      buprenorphine TDS is a well tolerated long-term analgesic for patients
      experiencing chronic musculoskeletal pain of moderate-to-severe intensity.

PMID- 20670048
TI  - Effects of opioid rotation in chronic pain patients: ORTIBARN study.
AB  - BACKGROUND: Opioid rotation is currently the subject of considerable debate for
      two reasons: firstly as a strategy for pain treatment, and secondly because of
      the difficulty in determining equianalgesic doses. Switching from one slow
      release (SR) opioid analgesic to another raises a number of critical issues, and
      there are no widespread studies that support a standard protocol. Initiation of
      opioid therapy must consider gradual dose titration of the drug until the minimum
      effective and maximum tolerated dosage for each patient is found. OBJECTIVE: This
      study aimed to evaluate the effects of SR opioid rotation after a stabilization
      period with normal-release (NR) morphine ('start therapy') in patients with
      cancer or non-cancer pain not controlled with their current SR opioid. METHODS:
      This is a multicentre, open-label, prospective study. A total of 326 consecutive
      patients were enrolled who were affected by chronic cancer or non-cancer pain
      that was not controlled by an SR opioid administered as either monotherapy or in
      combination with other analgesic drugs. Following start therapy with oral NR
      morphine at a dosage of 5 mg or 10 mg every 4 hours, rotation to an SR opioid of
      a different type from that previously administered was carried out. RESULTS:
      After about 3 days of start therapy with NR morphine, rotation to an SR opioid
      allowed a significant decrease of both baseline pain and daily episodes of
      breakthrough pain. No significant difference was detected between dosages and
      type of opioid administered, both prior to and after the start therapy period
      with NR morphine. CONCLUSIONS: Rotation to another opioid preceded by a brief
      period of opioid receptor resetting by start therapy with NR morphine allows a
      good level of pain control and avoids rotation to inappropriate opioid dosages or
      combinations analgesics.

PMID- 20670049
TI  - Time to pain relief after immediate-release morphine in episodic pain: the TIME
      study.
AB  - BACKGROUND: Cancer-related and non-cancer chronic pain embodies the most frequent
      challenge in clinical practice. Management of chronic pain and breakthrough pain
      (BTP) requires adjustments to the analgesic regimen to achieve adequate pain
      control. OBJECTIVE: To examine the time to achieve pain relief in patients who
      experienced intense episodic pain breakouts despite baseline therapy with
      analgesics. METHODS: This study was based on a 14-day observation period.
      Patients with either cancer-related or non-cancer pain who experienced >2
      intensive episodic pain breakouts per day were prescribed immediate-release (IR)
      morphine sulphate (10 mg to 20 mg as needed) every 4 hours (around-the-clock) and
      allowed one rescue dose of IR morphine (equal to one additional administration of
      the dosage taken at fixed times) for any episodic pain breakouts. Patients
      recorded time of administration and time taken to achieve partial or total relief
      of episodic pain breakout in daily diaries; in one study centre the diary was
      managed with the help of specialized medical attendants. Pain intensity and
      general wellbeing were assessed by a Numerical Rating Scale (NRS) and Karnofsky
      Performance Scale, respectively. Adverse events and sleep patterns were also
      recorded. RESULTS: Of 85 patients (mean age 62.67 +/- 14.3 years) enrolled, 14
      experienced pain from non-cancer degenerative diseases, and 71 had cancer-related
      pain. Following stabilization of background pain, the intensity of daily pain
      improved; NRS decreased from baseline to day 14 for cancer (from 5.63 to 1.98)
      and non-cancer (from 8.00 to 1.00) groups (both p < 0.0001). Patients' general
      wellbeing increased concomitantly. Around-the-clock therapy resulted in an
      immediate decrease in the number of intense episodic pain breakouts per day, with
      11.8% of patients achieving total pain relief within 24 hours. The mean number of
      intense episodic pain breakouts per day decreased steadily in the cancer group,
      reaching significance at day 14 (p < 0.001 vs baseline). Moreover, the time to
      achieve partial and total pain relief of intense episodic pain breakouts improved
      significantly. Adverse events and sleep patterns improved over the 14-day
      observation period. CONCLUSIONS: Stabilization of background cancer-related or
      non-cancer pain with around-the-clock IR morphine therapy resulted in fewer
      intense episodic pain breakouts, which were more quickly managed with rescue-dose
      IR morphine, suggesting that 'end-dose' pain should not be classified as BTP.

PMID- 20670050
TI  - Does graft construct lengthening at the fixations cause an increase in anterior
      laxity following anterior cruciate ligament reconstruction in vivo?
AB  - A millimeter-for-millimeter relation between an increase in length of an anterior
      cruciate ligament graft construct and an increase in anterior laxity has been
      demonstrated in multiple in vitro studies. Based on this relation, a 3 mm
      increase in length of the graft construct following surgery could manifest as a 3
      mm increase in anterior laxity in vivo, which is considered clinically unstable.
      Hence, the two primary objectives were to determine whether the millimeter-for
      millimeter relation exists in vivo for slippage-resistant fixation of a soft
      tissue graft and, if it does not exist, then to what extent the increase in
      stiffness caused by biologic healing of the graft to the bone tunnel offsets the
      potential increase in anterior laxity resulting from lengthening at the sites of
      fixation. Sixteen subjects were treated with a fresh-frozen, nonirradiated,
      nonchemically processed tibialis allograft. Tantalum markers were injected into
      the graft, fixation devices, and bones. On the day of surgery and at 1, 2, 3, and
      4 months, Roentgen stereophotogrammetric analysis was used to compute anterior
      laxity at 150 N of anterior force and the total slippage from both sites of
      fixation. A simple linear regression was performed to determine whether the
      millimeter-for-millimeter relation existed and a springs-in-series model of the
      graft construct was used to determine the extent to which the increase in
      stiffness caused by biological healing of the graft to the bone tunnel offset the
      increase in anterior laxity resulting from lengthening at the sites of fixation.
      There was no correlation between lengthening at the sites of fixation and the
      increase in anterior laxity at 1 month (R(2)=0.0, slope=0.2). Also, the increase
      in stiffness of the graft construct caused by biologic healing of the graft to
      the bone tunnel offset 0.7 mm of the 1.5 mm potential increase in anterior laxity
      resulting from lengthening at the sites of fixation. This relatively large offset
      of nearly 50% occurred because lengthening at the sites of fixation was small.

PMID- 20670051
TI  - Structured tree impedance outflow boundary conditions for 3D lung simulations.
AB  - In this paper, we develop structured tree outflow boundary conditions for
      modeling the airflow in patient specific human lungs. The utilized structured
      tree is used to represent the nonimageable vessels beyond the 3D domain. The
      coupling of the two different scales (1D and 3D) employs a Dirichlet-Neumann
      approach. The simulations are performed under a variety of conditions such as
      light breathing and constant flow ventilation (which is characterized by very
      rapid acceleration and deceleration). All results show that the peripheral
      vessels significantly impact the pressure, however, the flow is relatively
      unaffected, reinforcing the fact that the majority of the lung impedance is due
      to the lower generations rather than the peripheral vessels. Furthermore,
      simulations of a hypothetical diseased lung (restricted flow in the superior left
      lobe) under mechanical ventilation show that the mean pressure at the outlets of
      the 3D domain is about 28% higher. This hypothetical model illustrates potential
      causes of volutrauma in the human lung and furthermore demonstrates how different
      clinical scenarios can be studied without the need to assume the unknown flow
      distribution into the downstream region.

PMID- 20670052
TI  - The influence of modeling separate neuromuscular compartments on the force and
      moment generating capacities of muscles of the feline hindlimb.
AB  - Functional electrical stimulation (FES) has the capacity to regenerate motion for
      individuals with spinal cord injuries. However, it is not straightforward to
      determine the stimulation parameters to generate a coordinated movement.
      Musculoskeletal models can provide a noninvasive simulation environment to
      estimate muscle force and activation timing sequences for a variety of tasks.
      Therefore, the purpose of this study was to develop a musculoskeletal model of
      the feline hindlimb for simulations to determine stimulation parameters for
      intrafascicular multielectrode stimulation (a method of FES). Additionally, we
      aimed to explore the differences in modeling neuromuscular compartments compared
      with representing these muscles as a single line of action. When comparing the
      modeled neuromuscular compartments of biceps femoris, sartorius, and
      semimembranosus to representations of these muscles as a single line of action,
      we observed that modeling the neuromuscular compartments of these three muscles
      generated different force and moment generating capacities when compared with
      single muscle representations. Differences as large as 4 N m (approximately 400%
      in biceps femoris) were computed between the summed moments of the neuromuscular
      compartments and the single muscle representations. Therefore, modeling
      neuromuscular compartments may be necessary to represent physiologically
      reasonable force and moment generating capacities of the feline hindlimb.

PMID- 20670053
TI  - Mechanics of the mitral valve strut chordae insertion region.
AB  - Interest in developing durable mitral valve repair methods is growing,
      underscoring the need to better understand the native mitral valve mechanics. In
      this study, the authors investigate the dynamic deformation of the mitral valve
      strut chordae-to-anterior leaflet transition zone using a novel stretch mapping
      method and report the complex mechanics of this region for the first time. Eight
      structurally normal porcine mitral valves were studied in a pulsatile left heart
      simulator under physiological hemodynamic conditions -120 mm peak transvalvular
      pressure, 5 l/min cardiac output at 70 bpm. The chordal insertion region was
      marked with a structured array of 31 miniature markers, and their motions
      throughout the cardiac cycle were tracked using two high speed cameras. 3D marker
      coordinates were calculated using direct linear transformation, and a second
      order continuous surface was fit to the marker cloud at each time frame. Average
      areal stretch, principal stretch magnitudes and directions, and stretch rates
      were computed, and temporal changes in each parameter were mapped over the
      insertion region. Stretch distribution was heterogeneous over the entire strut
      chordae insertion region, with the highest magnitudes along the edges of the
      chordal insertion region and the least along the axis of the strut chordae. At
      early systole, radial stretch was predominant, but by mid systole, significant
      stretch was observed in both radial and circumferential directions. The
      compressive stretches measured during systole indicate a strong coupling between
      the two principal directions, explaining the small magnitude of the systolic
      areal stretch. This study for the first time provides the dynamic kinematics of
      the strut chordae insertion region in the functioning mitral valve. A
      heterogeneous stretch pattern was measured, with the mechanics of this region
      governed by the complex underlying collagen architecture. The insertion region
      seemed to be under stretch during both systole and diastole, indicating a
      transfer of forces from the leaflets to the chordae and vice versa throughout the
      cardiac cycle, and demonstrating its role in optimal valve function.

PMID- 20670054
TI  - HIFU lesion volume as a function of sonication time, as determined by MRI,
      histology, and computations.
AB  - Characterization of high-intensity focused ultrasound (HIFU) systems using ex
      vivo tissues is an important part of the preclinical testing for new HIFU
      devices. In ex vivo characterization, the lesion volume produced by the
      absorption of HIFU energy is quantified as operational parameters are varied.
      This paper examines the three methods used for lesion-volume quantification:
      histology, magnetic resonance (MR) imaging, and numerical calculations. The
      methods were studied in the context of a clinically relevant problem for HIFU
      procedures--that of quantifying the change in the lesion volume with changing
      sonication time. The lesion volumes of sonicated samples of porcine liver were
      determined using the three methods, at focal intensities ranging from 800 W/cm(2)
      to 1700 W/cm(2) and sonication times between 20 s and 40 s. It was found that
      histology consistently yielded lower lesion volumes than the other two methods,
      and the calculated values were below magnetic resonance imaging (MRI) at high
      applied energies. Still, the three methods agreed with each other to within a +/
      10% difference for all of the experiments. Increasing the sonication time
      produced much larger changes in the lesion volume than increasing the acoustic
      intensity, for the same total energy expenditure, at lower energy (less than 1000
      J) levels. At higher energy levels, (around 1500 J), increasing the sonication
      time and increasing the intensity produced roughly the same change in the lesion
      volume for the same total energy expenditure.

PMID- 20670055
TI  - Generalized anisotropic inverse mechanics for soft tissues.
AB  - Elastography, which is the imaging of soft tissues on the basis of elastic
      modulus (or, more generally, stiffness) has become increasingly popular in the
      last decades and holds promise for application in many medical areas. Most of the
      attention has focused on inhomogeneous materials that are locally isotropic, the
      intent being to detect a (stiff) tumor within a (compliant) tissue. Many tissues
      of mechanical interest, however, are anisotropic, so a method capable of
      determining material anisotropy would be attractive. We present here an approach
      to determine the mechanical anisotropy of inhomogeneous, anisotropic tissues, by
      directly solving the finite element representation of the Cauchy stress balance
      in the tissue. The method divides the sample domain into subdomains assumed to
      have uniform properties and solves for the material constants in each subdomain.
      Two-dimensional simulated experiments on linear anisotropic inhomogeneous systems
      demonstrate the ability of the method, and simulated experiments on a nonlinear
      model demonstrate the ability of the method to capture anisotropy qualitatively
      even though only a linear model is used in the inverse problem. As with any
      inverse problem, ill-posedness is a serious concern, and multiple tests may need
      to be done on the same sample to determine the properties with confidence.

PMID- 20670056
TI  - Finite element modeling of the influence of hand position and bone properties on
      the Colles' fracture load during a fall.
AB  - Distal forearm fracture is one of the most frequently observed osteoporotic
      fractures, which may occur as a result of low energy falls such as falls from a
      standing height and may be linked to the osteoporotic nature of the bone,
      especially in the elderly. In order to prevent the occurrence of radius fractures
      and their adverse outcomes, understanding the effect of both extrinsic and
      intrinsic contributors to fracture risk is essential. In this study, a nonlinear
      fracture mechanics-based finite element model is applied to human radius to
      assess the influence of extrinsic factors (load orientation and load distribution
      between scaphoid and lunate) and intrinsic bone properties (age-related changes
      in fracture properties and bone geometry) on the Colles' fracture load. Seven
      three-dimensional finite element models of radius were created, and the fracture
      loads were determined by using cohesive finite element modeling, which explicitly
      represented the crack and the fracture process zone behavior. The simulation
      results showed that the load direction with respect to the longitudinal and
      dorsal axes of the radius influenced the fracture load. The fracture load
      increased with larger angles between the resultant load and the dorsal axis, and
      with smaller angles between the resultant load and longitudinal axis. The
      fracture load also varied as a function of the load ratio between the lunate and
      scaphoid, however, not as drastically as with the load orientation. The fracture
      load decreased as the load ratio (lunate/scaphoid) increased. Multiple regression
      analysis showed that the bone geometry and the load orientation are the most
      important variables that contribute to the prediction of the fracture load. The
      findings in this study establish a robust computational fracture risk assessment
      method that combines the effects of intrinsic properties of bone with extrinsic
      factors associated with a fall, and may be elemental in the identification of
      high fracture risk individuals as well as in the development of fracture
      prevention methods including protective falling techniques. The additional
      information that this study brings to fracture identification and prevention
      highlights the promise of fracture mechanics-based finite element modeling in
      fracture risk assessment.

PMID- 20670057
TI  - A finite element model for direction-dependent mechanical response to
      nanoindentation of cortical bone allowing for anisotropic post-yield behavior of
      the tissue.
AB  - A finite element model was developed for numerical simulations of nanoindentation
      tests on cortical bone. The model allows for anisotropic elastic and post-yield
      behavior of the tissue. The material model for the post-yield behavior was
      obtained through a suitable linear transformation of the stress tensor components
      to define the properties of the real anisotropic material in terms of a
      fictitious isotropic solid. A tension-compression yield stress mismatch and a
      direction-dependent yield stress are allowed for. The constitutive parameters are
      determined on the basis of literature experimental data. Indentation experiments
      along the axial (the longitudinal direction of long bones) and transverse
      directions have been simulated with the purpose to calculate the indentation
      moduli and the tissue hardness in both the indentation directions. The results
      have shown that the transverse to axial mismatch of indentation moduli was
      correctly simulated regardless of the constitutive parameters used to describe
      the post-yield behavior. The axial to transverse hardness mismatch observed in
      experimental studies (see, for example, Rho et al. [1999, "Elastic Properties of
      Microstructural Components of Human Bone Tissue as Measured by Nanoindentation,"
      J. Biomed. Mater. Res., 45, pp. 48-54] for results on human tibial cortical bone)
      can be correctly simulated through an anisotropic yield constitutive model.
      Furthermore, previous experimental results have shown that cortical bone tissue
      subject to nanoindentation does not exhibit piling-up. The numerical model
      presented in this paper shows that the probe tip-tissue friction and the post
      yield deformation modes play a relevant role in this respect; in particular, a
      small dilatation angle, ruling the volumetric inelastic strain, is required to
      approach the experimental findings.

PMID- 20670058
TI  - Wedge indentation fracture of cortical bone: experimental data and predictions.
AB  - The fracture of bone due to indentation with a hard, sharp object is of
      significance in surgical procedures and certain trauma situations. In the study
      described below, the fracture of bovine bone under indentation was measured
      experimentally and predicted using the theory of critical distances (TCDs), a
      theory, which predicts failure due to cracking in the vicinity of stress
      concentrations. The estimated indentation fracture force was compared with the
      experimental results in three different cutting directions. Under indentation,
      the material experiences high levels of compression and shear, causing cracks to
      form and grow. The direction of crack growth was highly dependent on the bone's
      microstructure: major cracks grew in the weakest possible structural direction.
      Using a single value of the critical distance (L=320 microm), combined with a
      multiaxial failure criterion, it was possible to predict the experimental failure
      loads with less than 30% errors. Some differences are expected between the
      behavior of human bone and the bovine bone studied here, owing to its plexiform
      microstructure.

PMID- 20670059
TI  - Verification of predicted knee replacement kinematics during simulated gait in
      the Kansas knee simulator.
AB  - Evaluating total knee replacement kinematics and contact pressure distributions
      is an important element of preclinical assessment of implant designs. Although
      physical testing is essential in the evaluation process, validated computational
      models can augment these experiments and efficiently evaluate perturbations of
      the design or surgical variables. The objective of the present study was to
      perform an initial kinematic verification of a dynamic finite element model of
      the Kansas knee simulator by comparing predicted tibio- and patellofemoral
      kinematics with experimental measurements during force-controlled gait
      simulation. A current semiconstrained, cruciate-retaining, fixed-bearing implant
      mounted in aluminum fixtures was utilized. An explicit finite element model of
      the simulator was developed from measured physical properties of the machine, and
      loading conditions were created from the measured experimental feedback data. The
      explicit finite element model allows both rigid body and fully deformable
      solutions to be chosen based on the application of interest. Six degrees-of
      freedom kinematics were compared for both tibio- and patellofemoral joints during
      gait loading, with an average root mean square (rms) translational error of 1.1
      mm and rotational rms error of 1.3 deg. Model sensitivity to interface friction
      and damping present in the experimental joints was also evaluated and served as a
      secondary goal of this paper. Modifying the metal-polyethylene coefficient of
      friction from 0.1 to 0.01 varied the patellar flexion-extension and tibiofemoral
      anterior-posterior predictions by 7 deg and 2 mm, respectively, while other
      kinematic outputs were largely insensitive.

PMID- 20670060
TI  - The biomechanical consequence of insufficient femoral component lateralization
      and exposed cancellous bone in hip resurfacing arthroplasty.
AB  - Insufficient lateralization of the femoral component coupled with exposed reamed
      cancellous bone has been speculated to predispose to femoral neck fracture. The
      current study examined the effect of mediolateral implant position and exposed
      cancellous bone on the strength of the resurfaced proximal femur. Composite
      femurs were prepared in three configurations: (1) partial, with the implant
      placed at the native femoral head offset of the femur, partially exposing reamed
      cancellous bone; (2) proud, with a medialized implant exposing a circumferential
      ring of cancellous bone; and (3) complete, with a lateralized implant covering
      all reamed cancellous bone. Specimens were loaded to failure in axial
      compression. A finite element model was used to further explore the effect of
      exposed cancellous bone, cement mantle thickness, and relative valgus orientation
      on the strain distributions in the resurfaced femur. The proud group (2063 N) was
      significantly weaker than both the partial (2974 N, p=0.004) and complete groups
      (5899 N, p=0.001) when tested to failure. The partial group was also
      significantly weaker than the complete group when tested to failure (p=0.001).
      The finite element model demonstrated increasing levels of strain in the superior
      reamed cortical-cancellous bone interface with increasing degree of exposed
      cancellous bone. The condition of the femoral component medialized as the result
      of a thick cement mantle had the greatest detrimental impact on strain level in
      the superior reamed cancellous bone while a valgus oriented implant provided a
      protective effect. This study provides biomechanical evidence that exposed reamed
      cancellous bone significantly reduces the load-to-failure and increases maximum
      strains in the resurfaced proximal femur. The perceived benefit of reconstructing
      the femur to its native geometry may inherently weaken the proximal femur and
      increase femoral neck fracture risk if the femoral component is not sufficiently
      lateralized to cover all unsupported reamed cancellous bone. Relative valgus
      orientation of the implant may help to minimize the risk of neck fracture if
      reamed cancellous bone remains exposed following implant impaction.

PMID- 20670061
TI  - High strain rate testing of bovine trabecular bone.
AB  - In spinal vertebral burst fractures, the dynamic properties of the trabecular
      centrum, which is the central region of porous bone inside the vertebra, can play
      an important role in determining the failure mode. If the failure occurs in the
      posterior portion of the vertebral body, spinal canal occlusion can occur and
      ejected trabecular bone can impact the spinal cord resulting in serious injury.
      About 15% of all spinal cord injuries are caused by such burst fractures.
      Unfortunately, due to the uniqueness of burst fracture injuries, postinjury
      investigation cannot always accurately assess the degree of damage caused by
      these fractures. This research makes an effort to begin understanding the
      governing effects in this important bone fracture event. Measurements of the
      dynamic deformation response of bovine trabecular bone with the marrow intact and
      marrow removed using a modified split-Hopkinson pressure bar apparatus are
      reported and compared with quasistatic deformation response results. Because
      trabecular bone is more compliant and lower in strength than cortical bone,
      typical Hopkinson pressure bar experimental techniques used for high strain rate
      testing of harder materials cannot be applied. Instead, a quartz-crystal
      embedded, split-Hopkinson pressure bar developed for testing compliant, low
      strength materials is used. Care is taken into account for the orthotropic
      properties in the bone by testing only along the principle material axes,
      determined through microcomputed tomography. In addition, shaping of the stress
      wave pulse is used to ensure a constant strain rate and homogeneous specimen
      deformation. Results indicate that the strength of trabecular bone increases by a
      factor of approximately 2-3 when the strain rate increases from 10(-3) s(-1) to
      500 s(-1) and that the bone fractures beyond a critical strain.

PMID- 20670062
TI  - Endothelial cell morphologic response to asymmetric stenosis hemodynamics:
      effects of spatial wall shear stress gradients.
AB  - Endothelial cells are known to respond to hemodynamic forces. Their phenotype has
      been suggested to differ between atheroprone and atheroprotective regions of the
      vasculature, which are characterized by the local hemodynamic environment. Once
      an atherosclerotic plaque has formed in a vessel, the obstruction creates complex
      spatial gradients in wall shear stress. Endothelial cell response to wall shear
      stress may be linked to the stability of coronary plaques. Unfortunately, in
      vitro studies of the endothelial cell involvement in plaque stability have been
      limited by unrealistic and simplified geometries, which cannot reproduce
      accurately the hemodynamics created by a coronary stenosis. Hence, in an attempt
      to better replicate the spatial wall shear stress gradient patterns in an
      atherosclerotic region, a three dimensional asymmetric stenosis model was
      created. Human abdominal aortic endothelial cells were exposed to steady flow
      (Re=50, 100, and 200 and tau=4.5 dyn/cm(2), 9 dyn/cm(2), and 18 dyn/cm(2)) in
      idealized 50% asymmetric stenosis and straight/tubular in vitro models. Local
      morphological changes that occur due to magnitude, duration, and spatial
      gradients were quantified to identify differences in cell response. In the one
      dimensional flow regions, where flow is fully developed and uniform wall shear
      stress is observed, cells aligned in flow direction and had a spindlelike shape
      when compared with static controls. Morphological changes were progressive and a
      function of time and magnitude in these regions. Cells were more randomly
      oriented and had a more cobblestone shape in regions of spatial wall shear stress
      gradients. These regions were present, both proximal and distal, at the stenosis
      and on the wall opposite to the stenosis. The response of endothelial cells to
      spatial wall shear stress gradients both in regions of acceleration and
      deceleration and without flow recirculation has not been previously reported.
      This study shows the dependence of endothelial cell morphology on spatial wall
      shear stress gradients and demonstrates that care must be taken to account for
      altered phenotype due to geometric features. These results may help explain
      plaque stability, as cells in shoulder regions near an atherosclerotic plaque had
      a cobblestone morphology indicating that they may be more permeable to
      subendothelial transport and express prothrombotic factors, which would increase
      the risk of atherothrombosis.

PMID- 20670063
TI  - Effects of virus size and cell stiffness on forces, work, and pressures driving
      membrane invagination in a receptor-mediated endocytosis.
AB  - A continuum model based on the contact mechanics theory was developed and used
      for evaluating virus indentation forces at the early stage of membrane
      invagination, as well as the work of the virus indentation forces and virus-cell
      contact pressures in a receptor-mediated endocytosis, depending on the virus size
      and virus/cell stiffnesses. The model indicated that early virus indentation
      forces are in the order of 1-10 pN and for a given extent of virus engulfment,
      they increase linearly with the elastic modulus of the host cell and also with
      the square of the virus radius. The work of invagination at the initial phase of
      virus endocytosis is in the order of tens of zeptojoules and peak virus-cell
      contact pressures at this stage are in the order of hundreds of Pascals to
      several kPa. For a given extent of virus engulfment, peak and average contact
      pressures increase linearly with the elastic modulus of the host cell but
      interestingly, they are negligibly affected by the virus size. The present model
      may be useful in the fields of cellular biomechanics, virology and nanodrug
      delivery to evaluate mechanical factors during the early phase of membrane
      invagination.

PMID- 20670064
TI  - Measurements of the static friction coefficient between bone and muscle tissues.
AB  - This study aimed at measuring the static coefficient of friction (mu) between
      bone and skeletal muscle tissues in order to support finite element (FE) modeling
      in orthopaedic and rehabilitation research, where such contact conditions need to
      be defined. A custom-made friction meter (FM) that employs the load cell and
      motion-controlled loading arm of a materials testing machine was designed for
      this study. The FM was used to measure mu between fresh ulna bones and extensor
      muscles surrounding the ulna, which were harvested from five young adult pigs.
      Mean bone-muscle mu were between 0.36 and 0.29, decreased with the increase in
      loads applied on the bone (p<0.05) and plateaued at a mean approximately 0.3 for
      loads exceeding 4 N. Hence, for FE modeling of bone-muscle contacts through which
      loads with magnitudes of kgs to 10s-of-kgs are transferred, assuming mu of
      approximately 0.3 appears to be appropriate.

PMID- 20670065
TI  - Adult celiac disease - a common, significant health problem worldwide.

PMID- 20670066
TI  - Coeliac disease: clinical features in adult populations.
AB  - INTRODUCTION: coeliac disease (CD) is a chronic disease of the small intestine,
      which is caused by gluten intolerance, producing malabsorption of nutrients and
      vitamins. Clinical manifestations of CD in adults are highly variable, including
      intestinal and extra-intestinal symptoms. The disease may also occur in
      individuals who are asymptomatic. OBJECTIVE: our objective is to describe the
      incidence and clinical manifestations of CD in adults. MATERIAL AND METHODS: a
      retrospective study was carried out in patients diagnosed of CD between January
      1990 and December 2008. Diagnosis was based on serologic tests and duodenal
      biopsy, which were compatible with CD in all of them. RESULTS: sixty eight adult
      patients were diagnosed of CD in this period. Mean age was 33 (18-65) years and
      50 (74%) were women. The clinical manifestations were diarrhoea in 38 (55%),
      abdominal pain in 27 (40%), loss of weight in 15 (22%), dyspepsia in 13 (19%).
      Analytical results showed a slight increase of transaminases in 26 (38%),
      ferropenic anaemia in 33 (48.5%) cases, sub-clinical hypothyroidism in 3 (4.5%)
      patients, and folic acid deficiency in 16 (23.5%) cases. Almost all patients were
      diagnosed between 2000 and 2008: 60 (87%). Population-based incidence of CD in
      adults had increased from 0.7-2/100,000 per year in the nineties to 3.5
      10.3/100,000 in the last years. CONCLUSIONS: CD can appear at any age and with a
      wide manifestation spectrum, which can be atypical in some cases. Patients with
      ferropenic anaemia and a negative response to treatment or those with an
      unexplained increase in transaminases should be screening for CD. Atypical
      manifestations and low suspect index can delay diagnosis even during years. There
      is a marked increase in the incidence-rates of CD in adults over time.

PMID- 20670067
TI  - Coeliac disease in China, a field waiting for exploration.
AB  - BACKGROUND: no systematic studies on the prevalence of coeliac disease (CD) have
      been reported from China. In western populations CD is more common in patients
      with insulin dependent diabetes mellitus (IDDM) and in diarrhoea-predominant
      irritable bowel syndrome (D-IBS). We have screened patients with these conditions
      presenting to the outpatient department of a large hospital of "Traditional
      Chinese Medicine" (TCM) in Nanjing, Jiangsu province, P.R. China. METHODS: we
      tested sera of 78 unrelated Han Chinese patients (5 IDDM and 73 D-IBS), using
      ELISA serological tests for IgG anti-gliadin antibodies (IgG-AGA) and IgA anti
      tissue transglutaminase antibodies (IgA-tTG). RESULTS: six out of 78 patients
      (7.7%) were positive for IgG-AGA (two men and four women) and two (2.6%) were
      positive for IgA-tTGs. One of the latter patients was negative for IgG-AGA.
      Besides, one patient had a dubious IgA-tTG antibody and a positive IgG-AGA. None
      of the six patients agreed to undergo duodenal biopsy. Two out of these six
      patients followed a gluten-free diet for one year. In one patient the diarrhoea
      ceased and his body weight increased. Another stopped losing weight. CONCLUSIONS:
      this study previously published as a letter in GUT (Wu J, Xia B, von Blomberg
      BME, Zhao C, Yang XW, Crusius JBA, Pena AS. Coeliac disease: emerging in China?
      Gut 2010; 59(3): 418-9) demonstrated that CD may exist in the Jiangsu province of
      P.R. China. The present article draws attention to the difficulties of following
      a standard protocol in China such as established in western countries and
      highlights important factors less well known in the west in relation to the
      development of CD in China. Wheat production became significant in China between
      1600 and 1300 B.C. After the Han dynasty (500-200 B.C.), wheat was one of the
      main cereals in China. One the major wheat fields in China is located in the
      Jiangsu province where the research for this article was performed. A review of
      Chinese literature shows that the predominant HLA-DQ CD risk alleles and
      haplotypes are present in the Jiangsu province. Genetic background, food
      consumption, and the results of our study suggest that CD should actively be
      investigated in P.R. China.

PMID- 20670068
TI  - Usefulness of colonoscopy in ischemic colitis.
AB  - BACKGROUND: the ischemic colitis is intestinal the most frequent cause of
      ischemia. With this work we determine the demographic and clinical
      characteristics, and the usefulness of the colonoscopy in the patients with
      ischemic colitis diagnosed in our centre in relation to a change of therapeutic
      attitude. METHOD: retrospective study in which were selected 112 patients
      diagnosed with ischemic colitis by colonoscopy and biopsy, in a period of five
      years. It was analyzed: age, sex, reason for examination, factors of
      cardiovascular risk, endoscopic degree of ischemia, change in the therapeutic
      attitude, treatment and outcome. RESULTS: the average age was of 73.64 + or -
      12.10 years with an equal incidence in women (50.9%) and the men (49.1%). The
      associated factors were the HTA (61.1%), tobacco (37.2%) and antecedents of
      cardiovascular episode (52.2%). The most frequent reason for colonoscopy was
      rectorrhagia (53.6%) followed of the abdominal pain (30.4%), being urgent the
      65.3%. Colonoscopy allowed a change in the therapeutic attitude in the 50
      increasing in the urgent one to the 65.75%. Global mortality was of 27.67%. The
      serious ischemic colitis (25%) was more frequent in men (64.3%) in urgent
      indication (85.71%) and attends with high mortality (53.57%). Surgical treatment
      in the 57.14% was made with a good evolution in the 50%, whereas the patients
      with mild or moderate ischemic colitis had a better prognosis (favourable
      evolution in 80.95%) with smaller requirement of the surgical treatment (4.76%),
      p < 0.05. CONCLUSION: the colitis ischemic are more frequent in the older age.
      The most frequent symptoms are the rectorrhagia and the abdominal pain. The
      colonoscopy is a useful technique to evaluate the gravity and it induces a change
      of attitude according to the result of the same one. The evidence of a serious
      colitis supposed an increase of the necessity of surgery and worse prognosis.

PMID- 20670069
TI  - Are hepatocellular carcinoma surveillance programs effective at improving the
      therapeutic options.
AB  - AIM: to evaluate whether the current surveillance programs (ultrasonography and
      alpha-fetoprotein testing every six months) are successful in detecting patients
      in the early stages. MATERIAL AND METHODS: the health records of all patients
      diagnosed with hepatocellular carcinoma in Donostia Hospital between 2003 and
      2005 were reviewed retrospectively. Eighty-five patients (11 women and 74 men)
      were included in the study and demographic data, risk factors and clinical data
      were obtained. Patients were split into two groups according to whether or not
      they had been included in a surveillance program. RESULTS: seventy per cent of
      patients of the surveillance group is diagnosed in early stage opposite to 26.7%
      of patients in no surveillance group (p < 0.05). Thirteen patients cannot receive
      curative treatment in spite of the diagnosis in early stage (9 in the
      surveillance group and 4 in the no surveillance group. The global sensibility of
      the surveillance program in our series is 95%. CONCLUSIONS: current
      hepatocellular carcinoma surveillance programs, which comprise six-monthly
      ultrasonography and alpha-fetoprotein tests, are highly sensitive and effective.
      These programs result in the detection of hepatocellular carcinoma in its early
      stages, when potentially curative treatment may be offered.

PMID- 20670070
TI  - Multiple non-metastatic gastrointestinal stromal tumors. Differential features.
AB  - INTRODUCTION: gastrointestinal stromal tumors (GISTs) are specific, generally KIT
      (CD117)-positive, mesenchymal tumors of the digestive tract displaying KIT or
      PDGFRA gene mutations. Clinically, they tend to present as solitary tumors of the
      intestinal wall; more rarely, multiple tumors may occur in one or more organs.
      OBJECTIVE: to review the morphological, immunohistochemical and molecular
      features of multiple, non-metastatic forms of GIST. SOURCES: review of the
      literature on Medline, and authors own experience. CONCLUSIONS: multiples GISTs
      may occur in three different contexts: as spontaneous lesions (in both adults and
      children); due to familial GIST syndrome (autosomal dominant inheritance); or in
      association with specific syndromes (e.g. Carney s triad, Carney-Stratakis
      syndrome, type I neurofibromatosis). Outside these contexts, the existence of
      multiple GISTs is deemed to be the result of tumor metastasis, and therefore
      indicative of advanced-stage disease. Clinicians need to be aware of these
      variants, whose prognosis and treatment differ.

PMID- 20670071
TI  - Primary omental infarction as cause of non-surgical acute abdomen: imaging
      diagnosis.

PMID- 20670072
TI  - Appendagitis in post-laparotomy hernia.

PMID- 20670073
TI  - Adenocarcinoma of the rectum and anus in a patient with Crohn's disease treated
      with infliximab.
AB  - In the present paper, we report the case of a patient with long-standing Crohn s
      disease and multiple complications that, after receiving treatment with
      infliximab, was diagnosed with an adenocarcinoma of the rectum and anus that
      required radical surgery, later presenting multiple metastases. In the
      discussion, characteristics and major risk factors for colorectal cancer in
      patients with inflammatory bowel disease will be largely reviewed, and current
      studies will be analyzed in connection with the appearance of neoplasms in
      patients being treated with biologics.

PMID- 20670075
TI  - Littre s hernia: unusual find in inguino-scrotal hernial repair.

PMID- 20670076
TI  - Multifocal hepatic inflammatory pseudotumor: spontaneous regression in a diabetic
      patient.

PMID- 20670077
TI  - [Is Helicobacter pylori active infection increased or decreased in Crohn's
      disease?].

PMID- 20670078
TI  - [Metastatic gastric adenocarcinoma with microangiopathic hemolytic anemia].

PMID- 20670080
TI  - On time to veto the use of the word "appendagitis"?

PMID- 20670079
TI  - [Gastrointestinal metastasis from poorly differentiated neuroendocrine
      carcinoma].

PMID- 20670081
TI  - 'Commentary on: The research agenda for general practice/family medicine and
      primary health care in Europe. Part 4. Specific problem solving skills'.

PMID- 20670082
TI  - Research using electronic patient records in general practice. The EGPRN meeting
      in Bertinoro, Italy, May 2009.
AB  - The European General Practice Research Network organized an international
      workshop on research using electronic patient records in Bertinoro, Italy, in May
      2009. The authors were keynote speakers at the workshop, tasked with summarizing
      the theme research presentations on each of the two days of the meeting. The
      conference discussed the utility of capturing data in a way that can be
      appropriately analysed. In this application, the use of ICPC was repeatedly
      mentioned. Such research requires disciplined data entry and retrieval, and many
      times consistency in coding is a challenge, which may be met by definitions for
      coded classes. Quality of data is a concern in such research, and there were
      suggestions to involve the patients in improving the quality of their record.
      Clinicians are qualified to code data into electronic patient records accurately,
      capturing the fine nuances of the consultation. Income incentives, such as the
      Quality Outcomes Framework, run the risk of data distortion to improve financial
      gain. The role of all family doctors in research was emphasized, and the full
      potential of collecting data from family practice is practically achievable only
      through large databases collecting clinical records from every practice. EGPRN
      has dealt with this emerging theme in primary care research over the years.
      Interested family doctors are invited to attend future conferences to develop
      collaborative research projects using electronic patient records.

PMID- 20670083
TI  - The role of ultrasonography and FDG-PET in axillary lymph node staging of breast
      cancer.
AB  - BACKGROUND: The presence of axillary lymph node metastasis is the most important
      prognostic factor and an essential part of staging and prognosis of breast
      cancer. PURPOSE: To elucidate the usefulness and accuracy of ultrasonography
      (US), fluorodeoxyglucose positron emission tomography (FDG-PET) scan, and
      combined analysis for axillary lymph node staging in breast cancer. MATERIAL AND
      METHODS: A total of 250 consecutive breast cancer patients who had undergone US,
      FDG-PET, and sentinel lymph node biopsy (SLNB) before surgery from January 2005
      to December 2006 were included in the study. If an axillary lymph node had a
      length to width ratio <or=1.5 or cortical thickening >or=3 mm or compression of
      the hilum on US, focal hot uptake (maximal standardized uptake value, SUVmax
      >or=2.0) in the ipsilateral axilla on FDG-PET, it was considered to be a
      metastatic lymph node. In combined analysis of US and FDG-PET, the interpretation
      was considered positive if at least two of any of the criteria were met. Each
      imaging finding was compared with a pathologic report regarding the presence of
      axillary lymph node metastasis, the number of metastatic lymph nodes, and the T
      stage of the breast mass. RESULTS: Pathologically confirmed axillary lymph node
      metastasis was noted in 73 cases (29.2%). The mean number of metastatic lymph
      nodes in pathology was 3.1 +/- 3.2, and the size of breast cancer was 2.0 +/-
      1.04 cm. In the detection of lymph node metastasis, the diagnostic accuracy of US
      was 78.8% and that of FDG-PET was 76.4%. On combined US and FDG-PET, accuracy was
      improved (91.6%). The number of metastatic lymph nodes on pathology was
      correlated with the positivity of US and FDG-PET (P < 0.01). CONCLUSION: Combined
      evaluation of US and FDG-PET was a sensitive and accurate method for axillary
      lymph node staging in breast cancer.

PMID- 20670084
TI  - Use of rituximab in combination with high-dose methotrexate in the treatment of
      primary central nervous system lymphoma in a mycophenolate mofetil treated
      patient with lupus nephritis.

PMID- 20670085
TI  - A Phase I-II dose escalation study of fixed-dose rate gemcitabine, oxaliplatin
      and capecitabine every two weeks in advanced cholangiocarcinomas.
AB  - INTRODUCTION: Gemcitabine based regimens have been widely used in patients with
      advanced cholangiocarcinoma (CC), but no standard therapy exists. In this study
      we aimed to find the maximally tolerated dose (MTD) of a two-week schedule of
      fixed dose rate (FDR) gemcitabine (G), oxaliplatin (O) and capecitabine (C), and
      evaluate the safety and efficacy of this regimen in patients with advanced
      cholangiocarcinoma (CC). METHODS: In the Phase I part of the study a dose
      escalation schedule of FDR G, O and C, administered every two weeks, was
      performed in patients with solid tumours and no other treatments or advanced CC.
      In the Phase II part response rate, toxicity, progression-free survival (PFS) and
      overall survival was evaluated in patients with newly diagnosed advanced CC.
      RESULTS: Thirty-six patients entered the Phase I part and G 1 000 mg/m(2) day 1
      and 15, O 60 mg/m(2) day 1 and 15, and C 1 000 mg/m(2) BID day 1-7 and day 15-21
      were established as MTD. In the Phase II part, 41 patients with advanced CC were
      included. Overall response rate was 34% and 51% had stable disease, resulting in
      a clinical benefit rate of 85%. Grade III and IV adverse events were rare. Median
      survival was 12.5 months (95% CI 9.2-15.9) and median progression-free survival
      (PFS) was 6.9 months (95% CI 5.1-8.6). CONCLUSIONS: This outpatient regimen was
      very feasible with significant activity and a favourable safety profile. Further
      studies will explore this combination with addition of newer targeted agents.

PMID- 20670086
TI  - What's the role of surgery in the management of primary thyroid lymphoma?

PMID- 20670087
TI  - Useful genetic variation databases for oncologists investigating the genetic
      basis of variable treatment response and survival in cancer.
AB  - Identification of the genetic basis of variable treatment response, prognosis and
      survival in cancer patients (i.e. personalized medicine) is an important aim in
      current medicine. Millions of genetic variations exist in the human genome, some
      of which are already found to be directly involved in variable treatment response
      and survival among cancer patients. GENETIC VARIATION DATABASES: Special
      databases curate, compile, organize and post information related to these genetic
      variations for the scientific community in a user friendly and free-to-access
      manner via the World Wide Web. FUTURE DIRECTIONS AND CONCLUSION: Clinicians have
      a critical role in genetic predictive and prognostic studies. In this review,
      main public-domain databases on genetic variations, including the two
      comprehensive genetic variation databases (dbSNP and HapMap), a pharmacogenomics
      database (PharmGKB), two resequencing-based genetic variation databases
      (SeattleSNPs and EGP), a population-based genetic variation database (JSNPs), and
      a copy-number variant database (DGV), and their utility in cancer research are
      discussed. Utilization of these databases can assist clinicians in their studies
      related to treatment response and prognosis in cancer patients.

PMID- 20670088
TI  - Hyposensitization in the treatment of resistant cases of vernal
      keratoconjunctivitis.
AB  - PURPOSE: The study evaluated the treatment of resistant cases of vernal
      keratoconjunctivitis by hyposensitization resulting from intradermal skin
      reactions of different allergens. METHODS: This prospective study was carried out
      in the Department of Ophthalmology and the Department of Microbiology and
      Immunology, Zagazig University, and included 36 patients with bilateral vernal
      keratoconjunctivitis that was resistant to topical corticosteroids and
      antihistaminic drugs. Patients were subjected to intradermal skin reactions to
      different allergens after stoppage of the medication. Subcutaneous injections of
      different allergens were administered in addition to topical vasoconstrictor and
      antihistaminic eye drops for different durations of 12, 18, and 24 months.
      RESULTS: The study revealed that most of the patients were sensitive to pollens
      (65%), house dust (55%), and tobacco smoke (40%). Among 36 total patients who
      received different doses of allergens, 10 of 20 patients showed marked
      improvement following a 24-month treatment period, with a 50% success rate.
      Another 3 of 9 patients showed marked improvement following an 18-month treatment
      period, with a 33.3% success rate. CONCLUSION: The use of intradermal skin
      reactions to determine the sensitivity for different stimulating allergens in
      resistant cases of vernal keratoconjunctivitis was conclusive. Treatment by
      hyposensitization using prepared vaccines had an acceptable success rate
      especially in patients treated for 24 months. Future studies will be needed to
      determine how effective this treatment is with other allergens and for longer
      durations of hyposensitization. Additional immunologic studies will be essential
      for developing a strategy of management of resistance in such cases of resistant
      vernal keratoconjunctivitis.

PMID- 20670089
TI  - Recovery of orbital fat pad prolapsus and deepening of the lid sulcus from
      topical bimatoprost therapy: 2 case reports and review of the literature.
AB  - OBJECTIVES: To report 2 cases of resolution of orbital fat pad prolapsus and
      deepening of the lid sulcus caused by topical bimatoprost therapy, and to review
      the literature. METHODS: This was a retrospective, observational chart review.
      RESULTS: A 54-year-old man with normotensive glaucoma presented with recovery of
      left lower lid orbital fat pad prolapsus, deepening of the lid sulcus, and iris
      color and eyelash changes 8 months after initiation of bimatoprost therapy in his
      left eye (OS). After stopping bimatoprost, his eyelashes and the lower lid
      orbital fat pad partially regained their natural appearance at 2 months and 4
      months, respectively. However, there was no improvement of the left upper eyelid
      deepening and the iris hyperpigmentation, even after 30 months. A 75-year-old man
      with unilateral pseudoexfoliative glaucoma had been treated with bimatoprost OS.
      Three months after initiation of the therapy, his examination showed recovery of
      the inferior and superomedial orbital fat pad prolapsus, a deep and prominent
      upper lid sulcus with eyelash changes, and iris hyperpigmentation OS. Five months
      after discontinuation of bimatoprost, the eyelashes and superomedial orbital fat
      pad improved. Twenty-four months later, the inferior orbital fat pad partially
      got its natural appearance back, but the upper lid sulcus was slightly more deep
      and prominent than the fellow right eye. There was no alteration in iris
      hyperpigmentation. CONCLUSION: Clinicians and patients should be aware of these
      possible effects of topical bimatoprost therapy. These adverse effects may not be
      completely reversible after discontinuation of the medication.

PMID- 20670090
TI  - Toxic anterior segment syndrome presenting as isolated cystoid macular edema
      after removal of entrapped ophthalmic ointment.
AB  - We report a case of ophthalmic antibiotic ointment in the anterior chamber
      following uneventful phacoemulsification surgery. Antibiotic ointment was
      observed in the superior angle beneath the clear corneal wound one month later.
      The patient remained asymptomatic for 26 months after surgery until mild iritis
      developed. The ointment was removed through a limbal incision superiorly via
      passive expression. Visual acuity declined to 20/200 after explantation on
      postoperative day one. Fluorescein angiography revealed cystoid macular edema.
      The treatment was refractory to topical steroid and non-steroid anti-inflammatory
      drugs, however responded well to intravitreal triamcinolone injection. Ophthalmic
      ointments may ingress into the anterior chamber through unstable clear corneal
      incisions. Although a globule of ointment may remain inert for a long time, its
      delayed extraction may be associated with cystoid macular edema.

PMID- 20670091
TI  - Neutropenic enterocolitis during first-line chemotherapy with carboplatin and
      etoposide in small cell lung cancer.

PMID- 20670092
TI  - Pulmonary blastoma in adult: dramatic but transient response to doxorubicin plus
      ifosfamide.

PMID- 20670093
TI  - The prevalence of congenital varicella syndrome after a maternal infection, but
      before 20 weeks of pregnancy: a prospective cohort study.
AB  - OBJECTIVE: To describe the prevalence of congenital varicella syndrome (CVS)
      within the population of presumably infected pregnant women. METHODS: From 1993
      to 2006, all women who presented vesicular rash or a suspicious contact were
      referred and evaluated in a special unit at our center. Those with residual
      immunity or were serologically negative were precluded from this study. Positive
      IgM cases underwent monthly ultrasound scans (US), fetal blood (FB) sampling
      (including IgM anti VZV and virus culture). Amniotic fluid sample for PCR was
      added to the diagnosis of positive IgM cases after 1997. RESULTS: A total of 276,
      of the 566 consulted women, tested positive for IgM anti VZV. Seventeen (6%) were
      excluded because of an unadvised termination of pregnancy and seven (2.55%)
      miscarried. Only seven (2.7%) were considered highly likely to have a VZV fetal
      infection. One case showed positive IgM in FB but developed normally. Another
      fetus showed positive PCR and infection was confirmed post TOP. Four cases that
      underwent TOP and histochemistry confirmed no more cases. Complete post-natal
      follow-up was carried out. The asymptomatic infected child grew healthy until the
      completion of screening tests when it reached 5 years old. CONCLUSION: The fetal
      infection rate in this cohort was 0.8%, but the best expected prevalence of CVS,
      according to our findings, should be 0.39% among infected women. This data should
      be considered and used during parental counselling.

PMID- 20670094
TI  - Fetal fibronectin as a predictor of spontaneous preterm birth: a European
      perspective.
AB  - Preterm birth (PTB) is estimated to account for 6-10% of all births worldwide
      with 13 million PTBs occurring annually and 1 million resulting in death. The
      diagnosis of spontaneous preterm labor and accurate prediction of preterm
      delivery is notoriously difficult. Identification of effective risk assessment
      markers can potentially improve outcomes by enabling targeted therapy while
      allowing efficient use of resources and avoiding unnecessary interventions.
      Advances in perinatal medicine have not reduced PTB and effective measures that
      improve outcome are yet to be established. However, considerable progress has
      been made in the development of accurate methods (fetal fibronectin and cervical
      length assessment) to predict PTB in both symptomatic and asymptomatic high-risk
      women. The excellent negative predictive value of fFN has the ability to
      facilitate decision-making regarding admission, in utero transfer, administration
      of antenatal corticosteroids and/or tocolysis and has been shown to be cost
      effective. This review describes the European perspective on the use of fFN and
      describes ongoing European clinical studies, which are appropriately designed
      with meaningful endpoints, which will undoubtedly facilitate a better
      understanding of test accuracy and cost-effectiveness within different
      populations.

PMID- 20670095
TI  - High mean platelet volume, low-grade systemic coagulation, and fibrinolytic
      activation are associated with pre-term delivery and low APGAR score in
      intrahepatic cholestasis of pregnancy.
AB  - OBJECTIVES: This study was designed for evaluating coagulation parameters and low
      APGAR scores in pregnancies with intrahepatic cholestasis of pregnancy (ICP) vs.
      normal control pregnancies. METHODS: We carried out a prospective case-control
      study by enrolling 40 women with ICP at the third trimester of pregnancy and 40
      pregnant women without ICP. RESULTS: Total bile acid levels (TBA), MPV, D-dimer,
      and umbilical artery systolic/diastolic ratio (UASDR) values were higher in women
      with ICP. Pregnancies complicated by low APGAR score exhibited significantly
      higher D-dimer levels than those of unimpaired fetal outcome in patients with ICP
      and control subjects. Levels of D-dimer were inversely correlated with 5'-Apgar
      score and positively associated with UASDR values in patients with ICP.
      Pregnancies that exhibited abnormal UASDR had higher total bile acid (TBA), D
      dimer, MPV values and lesser 5'-Apgar score. In linear stepwise regression
      analyses, D-dimer independently and positively associated with UASDR, inversely
      associated with 5'-Apgar score in subjects with ICP; positively associated with
      mean platelet volume (MPV) values and inversely associated with 5'-Apgar score in
      all subjects. CONCLUSION: Patients with ICP had low-grade systemic coagulation
      and fibrinolytic activation as evidenced by elevated D-dimer, and also D-dimer is
      associated with lower APGAR scores in both ICP and all pregnancies. Increased D
      dimer levels suggest that hematological parameters could be potentially used as
      indicators of risk factor for assessing low APGAR score in ICP.

PMID- 20670096
TI  - Cardiovascular risk assessment with oxidised LDL measurement in postmenopausal
      women receiving intranasal estrogen replacement therapy.
AB  - OBJECTIVE: To investigate the effect of intranasal estrogen replacement therapy
      administered to postmenopausal women alone or in combination with progesterone on
      markers of cardiovascular risk. METHODS: The study was conducted with 44
      voluntary postmenopausal women. In group I (n = 15), the patients were treated
      with only intranasal estradiol (300 MUg/day estradiol hemihydrate). In group II
      (n = 11), the patients received cyclic progesterone (200 mg/day micronized
      progesterone) for 12 days in each cycle in addition to continuous intranasal
      estradiol. Group III (n = 18) was the controls. Serum lipid profiles, oxidised
      low-density lipoprotein (LDL) and other markers of cardiovascular risk were
      assessed at baseline and at the 3rd month of the treatment. RESULTS: Lipid
      profile, LDL apolipoprotein B, lipoprotein a, homocysteine, oxidised LDL values
      and oxidised LDL/LDL cholesterol ratio were not observed to change after 3 months
      compared to baseline values within each group (p > 0.016). In comparison to
      changes between the groups after the treatment, only oxidised LDL levels and
      oxidised LDL/LDL cholesterol ratios of group II were increased compared to
      control group (p < 0.05). CONCLUSIONS: Intranasal estradiol alone did not appear
      to have an effect on markers of cardiovascular risk in healthy postmenopausal
      women. However, the addition of cyclic oral micronized progesterone to intranasal
      estradiol influenced the markers of cardiovascular risk negatively in comparison
      to non-users in healthy postmenopausal women.

PMID- 20670097
TI  - How do levonorgestrel-only emergency contraceptive pills prevent pregnancy? Some
      considerations.
AB  - Controversial opinions exist about the possible mechanisms throughout emergency
      contraception prevents pregnancy. Recently, the International Federation of
      Gynaecology and Obstetrics and the International Consortium for Emergency
      Contraception released a Joint Statement declaring that 'inhibition or delay of
      ovulation should be their primary and possibly only mechanism of action'. They
      still added that 'Review of the evidence suggests that LNG-ECPs cannot prevent
      implantation'. Concerning levonorgestrel-only emergency contraceptive pills
      effects on ovulation, the Statement based on seven reference papers which
      considered a total of only 142 patients, divided into still different subgroups.
      Basing on their same references we got quite different conclusions.

PMID- 20670098
TI  - Metabolic syndrome in Argentine women: ATPIII, IDF, IDF/AHA/NHLBI; what criterion
      should be used?
AB  - INTRODUCTION: The menopause and the metabolic syndrome (MS) are related with the
      increase of the risk of cardiovascular diseases. OBJECTIVES: To evaluate the
      existence of metabolic risk factors and the prevalence of MS in pre- and post
      menopausal women. SUBJECTS: 253 women: 120 pre-menopausal and 133 post
      menopausal. Anthropometric, arterial pressure and waist circumference
      measurements were carried out. Glycaemia, lipids, creatinine, hepatogram, uric
      acid and thyroid-stimulating hormone were dosed. RESULTS: Statistical higher
      registries of arterial pressure, levels of glycaemia, total cholesterol, low
      density lipoprotein, triglycerides and TG/high-density lipoprotein relation were
      observed among post-menopausal patients. As regards this group, the MS diagnosis
      was considerably higher, being the same by all the criteria. CONCLUSIONS: We
      found more prevalence of cardiometabolic and MS risk factors among the group of
      post-menopausal patients. The responsible mechanisms would respond to the
      secondary hypoestrogenaemia at the cease of the ovarian function. Because of this
      fact, menopausal women should be considered a risk group for the development of
      MS.

PMID- 20670099
TI  - Baseline psychological stress and ovarian norepinephrine levels negatively affect
      the outcome of in vitro fertilisation.
AB  - OBJECTIVE: We determined the effect of baseline psychological stress and
      norepinephrine (NE) levels in the follicular fluid on the outcome of in vitro
      fertilisation (IVF). METHODS: One hundred seven women with tubal factor
      infertility were evaluated before and during their first IVF treatment. On the
      first day of down-regulation, their psychological state was measured using the
      Zung Self-rating Anxiety (SAS) and Depression Scales (SDS), and defined as
      baseline psychological stress. On oocyte retrieval day, NE levels in the
      follicular fluid and peripheral plasma were measured by high-performance liquid
      chromatography. RESULTS: On the first day of down-regulation, nearly 10% of the
      women with tubal factor infertility reported that they were experiencing both
      anxiety and depression. This baseline psychological stress was lower in pregnant
      (3.7%) than in non-pregnant women (15.7%, p<0.05). On oocyte retrieval day, the
      NE levels in follicular fluid were almost twice the amount seen in peripheral
      plasma, but did not differ in pregnant and non-pregnant women (p>0.05). NE levels
      in follicular fluid were negatively associated with the percentage of good
      quality embryos (r= -0.62, p<0.05). CONCLUSIONS: Baseline psychological stress
      (both anxiety and depression) may negatively influence the clinical pregnancy
      rate of IVF treatment in women with tubal factor infertility. Furthermore,
      follicular NE levels are negatively associated with the percentage of good
      quality embryos.

PMID- 20670100
TI  - The correlation between clinical laboratory data and telomeric status of male
      patients with metabolic disorders and no clinical history of vascular events.
AB  - The telomere length and subtelomeric methylated status of peripheral blood
      leukocytes has been reported to be correlated with many kinds of
      pathophysiological conditions. However, the correlation between the telomeric
      parameters and clinical laboratory data in metabolic disorders is not well known.
      This study investigated the correlation between the telomere length and
      subtelomeric methylated status in peripheral leukocytes and the laboratory data
      of male outpatients with combined metabolic disorders and no clinical history of
      cardiovascular or cerebrovascular event were assessed, to find good clinical
      laboratory markers reflecting the biological aging. The laboratory data were
      collected in 26 Japanese male outpatients with diabetes mellitus and
      hyperlipidemia, and no history of cardiovascular or cerebrovascular event, and
      the telomeric parameters in their peripheral leukocytes were determined by
      Southern blot with methylation-sensitive and insensitive isoschizomers. Any
      correlations between the laboratory data and the telomeric parameters were
      assessed. The patients showed a significant negative correlation among the
      bilirubin and creatine phosphokinase with the aging-associate change of the
      telomeric and subtelomeric parameters. Lowered serum bilirubin and creatinine
      phosphokinase level correlated to genomic aging represented by telomere attrition
      of patients with metabolic disorders.

PMID- 20670101
TI  - Should frailty be treated with testosterone?

PMID- 20670102
TI  - Physical function and health-related quality-of-life in a population-based
      sample.
AB  - BACKGROUND. It is of interest to understand whether impaired physical function is
      associated with health-related quality-of-life (HRQOL). We examined upper and
      lower body physical function and its relationship with two domains of HRQOL among
      men. METHODS. We conducted a population-based observational study of
      musculoskeletal health among Boston, MA residents, the Boston Area Community
      Health/Bone Survey. Participants were 1219 randomly-selected Black, Hispanic, and
      White males (30-79 years). Upper body function was measured using hand grip
      strength, while lower body function was measured by combining a timed walk and a
      chair stand test. HRQOL was measured using the physical (PCS-12) and mental
      health (MCS-12) component scores of the SF-12. Multivariate linear regression
      models were used to estimate the association between poor function and HRQOL.
      RESULTS. There was a significant association of poor upper body physical function
      with the MCS-12 (beta coefficient: -4.12, p = 0.003) but not the PCS-12 (beta
      coefficient: 0.79, p = 0.30) compared to those without poor function. Those with
      poor lower body physical function had significantly lower PCS-12 scores (beta: 
      2.95, p = 0.007), compared to those without poor function, but an association was
      not observed for MCS-12 scores. CONCLUSIONS. Domains of physical function were
      not consistently related to domains of HRQOL.

PMID- 20670103
TI  - Association of testicular p63 expression and spermatogenesis in androgen receptor
      knockout (ARKO) mice.
AB  - OBJECTIVE: To study changes of testicular p63 expression and its effect on
      spermatogenic function in seminiferous tubules in androgen receptor knockout
      (ARKO) mice. METHODS: A total of 28 ARKO mice (ARKO group) screened by Cre-lox
      and 28 male Wistar mice without ARKO (controlled group) were enrolled in our
      study. Route pathology was performed and p63 examination was detected by
      immunohistochemistry in testes. Linear correlations were used to explore
      potential associations between p63 protein expression and spermatogenic function
      (TMS score). RESULTS: In ARKO group, inner diameter of seminiferous tubules was
      decreased (62 +/- 1.3 microm vs. 91 +/- 1.2 microm), thickness of the basal
      membrane of the tubules (4 +/- 0.3 microm vs. 2.7 +/- 0.5 microm), cellular
      population within tubules was reduced (2 +/- 0.4 vs. 4 +/- 0.1 layers), degree of
      spermatogenesis within the tubules turned to disturbance (3 +/- 1.0 vs. 5 +/-
      0.1), Testicular Makler score was lower than controlled group (7 +/- 0.2 vs.15 +/
      0.3), they had significant differences (p <0.01). P63 expressed significantly
      lower in ARKO group than that in Wistar group, and was limited at stages from
      spermatocyte to round spermatid. (Percentage of positive cells ? 68.1 +/- 3.7 vs.
      81.7 +/- 5.1, p<0.001). The HSCORE yielded similar results (HSCORE 3.7 +/- 0.3
      vs. 2.0 +/- 0.2, p<0.001). p63 protein expression was significantly positively
      correlated with spermatogenic function (r=0.87, p<0.01). CONCLUSIONS: p63
      developed important effect on spermatogenesis and the regulatory effect of p63 on
      spermatogenesis mainly occurred in the early stage of spermiogenesis in testis.

PMID- 20670104
TI  - A portable system for the assessment of neuromuscular diseases with electrical
      impedance myography.
AB  - PRIMARY OBJECTIVE: To create a system for the acquisition of multi-angle,
      multifrequency muscle impedance data. RESEARCH DESIGN: Device development and
      preliminary testing. METHODS AND PROCEDURES: The system presented here employs an
      interrogating signal composed of multiple tones with frequencies between 10 kHz
      and 300 kHz. The use of a composite signal makes possible measurement of
      impedance at multiple frequencies simultaneously. In addition, this system takes
      impedance measurements at multiple orientations with respect to the muscle fibres
      by means of an electronically reconfigurable electrode array. The required
      measurement time is reduced by taking advantage of muscle's linearity with
      respect to the flow of electrical current. MAIN OUTCOMES AND RESULTS: The system
      was tested in normal subjects, a patient with amyotrophic lateral sclerosis, and
      one with inclusion body myositis; unique impedance signatures were identified the
      two patients. CONCLUSIONS: Early data suggest that this system is capable of high
      quality data collection and may detect changes in neuromuscular disease; study of
      additional normal subjects and patients with a variety of neuromuscular diseases
      is warranted.

PMID- 20670105
TI  - Recovery of platelet factor 4 (PF-4) and beta-thromboglobulin (beta-TG) plasma
      concentrations during remission in patients suffering from atopic dermatitis.
AB  - Our previous study has for the first time demonstrated that atopic dermatitis
      (AD) patients show enhanced plasma concentrations of PF4 and beta-TG. In
      addition, it has been suggested that chemokines may be the markers of AD
      severity. The aim of this study was to determine whether enhanced platelet
      activation in active AD withdraws when the disease reaches the clinical remission
      stage. Plasma PF-4 and beta-TG concentrations were studied in 10 AD patients and
      in 23 healthy controls. Patients were examined twice: first, during the active
      period, and next, during the clinical remission lasting for at least 6 months.
      Plasma PF-4 and beta-TG concentrations in patients upon AD remission were
      significantly lower as compared to active AD and did not differ significantly
      from the healthy subjects. Enhanced platelet activation is a transient phenomenon
      accompanying active AD and disappears during clinical remission. As with earlier
      data, the findings point to platelet activity in AD increasing during flare,
      falling following therapy and normalizing upon remission.

PMID- 20670106
TI  - Protein phosphatase inhibitor calyculin-A modulates activation markers in TRAP
      stimulated human platelets.
AB  - Platelet activation is accompanied with the phosphorylation of a number of
      proteins on serine (Ser) and threonine (Thr) residues. The phosphorylation level
      of these proteins is dependent upon the protein kinase/phosphatase activity
      ratio. The aim of this study was to investigate the consequences of inhibiting
      protein phosphatase 1 (PP1) and 2A (PP2A) on platelet functions. Protein
      phosphatases were inhibited by preincubation of platelet rich plasma (PRP)
      samples with calyculin-A (CLA). Subsequently, platelets were activated by
      thrombin-receptor activating peptide (TRAP) and platelet aggregation, platelet
      derived microparticle (PMP) formation, surface expressions of P-selectin (CD62),
      lysosome-associated membrane protein (CD63), glycoprotein Ib and IIb were
      examined. Phosphatase activity was determined by using phosphorylated 20 kDa
      myosin light chain (P-MLC20) as substrate. In CLA-treated platelets substantial
      decrease of P-MLC20 phosphatase activity was observed. CLA significantly
      suppressed TRAP-induced surface expression of P-selectin and CD63 in a
      concentration-dependent manner as compared to non-treated samples and moderately
      decreased platelet aggregation. In TRAP-activated samples, 50 nM of CLA
      pretreatment completely abolished the level of PMPs and the prevention of GPIb
      downregulation was also observed; however, no difference was found in GPIIb
      expression. In conclusion, PP1 and PP2A-catalyzed dephosphorylation processes
      have crucial roles in PMP formation and in the regulation of alpha-granule and
      lysosome secretion in human platelets.

PMID- 20670107
TI  - Intra-individual variability in clopidogrel responsiveness in coronary artery
      disease patients under long term therapy.
AB  - Clopidogrel responsiveness (CR) following a loading dose (LD) predicts thrombotic
      events after percutaneous coronary interventions (PCI). Some of the mechanisms
      involved in large inter-individual variability in CR may be varied. We therefore
      postulated that there may be an intra-individual variability in CR. Two hundred
      and one patients receiving long-term therapy with aspirin and clopidogrel after
      drug-eluting stents PCI were prospectively included in this monocentre study
      along with any patient re-admitted within 12 months post-PCI. Platelet reactivity
      (PR) inhibition was assessed by the vasodilator phosphoprotein (VASP) index
      following a 600 mg loading dose of clopidogrel on each admission to determine CR
      (VASP 1 during the first admission and VASP 2 during re-admission). DeltaVASP =
      VASP 2 &#x2013;VASP 1 was used to study intra-individual variability in CR. We
      observed that the response to a 600 mg LD of clopidogrel was poorly correlated
      within an individual (kappa = 0.33; p < 0.001 (n = 201)). Although most patients
      had increased platelet inhibition at the time of readmission, 35.3% of patients
      exhibited a decreased platelet inhibition despite chronic clopidogrel therapy and
      a 600 mg reload. Quartiles analysis of DeltaVASP demonstrated that insulin
      treated diabetes was associated with decreased CR over time (p = 0.03). In
      addition to the large inter-individual variability in clopidogrel responsiveness,
      there is large intra-individual variability. Decreased clopidogrel responsiveness
      despite long-term clopidogrel therapy could be a trigger for recurrent thrombotic
      events.

PMID- 20670108
TI  - Bioconversion of silver salt into silver nanoparticles using different
      microorganisms.
AB  - Abstract: Recently, silver nanoparticles have generated enough interest due to
      their immense usage. Until now chemical synthesis has been a fast method to
      produce nanoparticles, but the release of environmental pollutants has raised
      caution. So a more subtle biochemical approach is in research. Three
      microorganisms, Aspergillus flavus, Phoma exigua and Bacillus megaterium, were
      selected to reduce silver nitrate to silver nanoparticles in aqueous form. All
      three microorganisms showed varying reducing capacity, of which Phoma exigua
      showed the highest, when their biomass was incubated in silver nitrate for 48
      hours. The nanoparticles showed all the optical and physical properties, which
      were analyzed by measuring the surface plasmon resonance and TEM. It was also
      observed that the fungal species have varied growth in silver nitrate and can be
      used to produce silver nanoparticles, directly incubating the inocula of fungus
      in the media containing silver nitrate. On comparing all the characteristics and
      results produced, Aspergillus flavus was found to be the most effective
      microorganism, which can convert the silver nitrate to silver nanoparticles in
      aqueous condition. The bacterial species showed no growth with incubation with
      silver nitrate.

PMID- 20670109
TI  - Protection against radiation-induced oxidative damage by an ethanolic extract of
      Nigella sativa L.
AB  - PURPOSE: An ethanolic extract of Nigella sativa L. (EE-NS) was investigated for
      its antioxidant properties and radioprotective effects against gamma-radiation
      induced oxidative damage. MATERIALS AND METHODS: The radical scavenging activity
      of the extract was measured by 2,2-diphenyl-1-picrylhydrazyl (DPPH), deoxyribose
      degradation and plasmid relaxation assays in a cell-free system. DNA damage
      studies were performed using a single cell gel electrophoresis (SCGE) assay and
      micronuclei (MN) formation. Moreover, the alterations in lipid peroxidation and
      antioxidant enzymes were measured by biochemical methods. RESULTS: EE-NS showed
      significant free radical scavenging and protection against DNA damage in cell
      free systems. Ex vivo treatment of mouse splenic lymphocytes with an ethanolic
      extract of N. sativa 1 h prior to irradiation (2 Gy) showed significant
      prevention of the formation of lipid-peroxides and intracellular reactive oxygen
      species (ROS), which correlated with radiation-induced apoptosis. Moreover,
      radiation-induced DNA damage was significantly prevented in splenocytes pre
      treated with EE-NS. Swiss albino mice fed orally with the different doses of EE
      NS (0-100 mg/kg bw) for five consecutive days followed by 2 Gy whole body
      irradiation (WBI) showed significant protection against oxidative injury to
      spleen and liver as measured by lipid peroxidation and the activity of
      antioxidant enzymes. These results were correlated with the prevention of DNA
      damage as measured by bone marrow micronuclei assay. Our results suggest that
      oral feeding of extract resulted in increased survival in mice exposed to WBI
      (7.5 Gy). CONCLUSION: The results obtained from the different experimental
      systems suggest the radioprotective ability of EE-NS involving prevention of
      radiation-induced oxidative damage.

PMID- 20670110
TI  - Natural radionuclides in fish species from surface water of Bagjata and
      Banduhurang uranium mining areas, East Singhbhum, Jharkhand, India.
AB  - PURPOSE: To study the natural radionuclides in the freshwater fish samples around
      the uranium mining areas of Bagjata and Banduhurang, East Singhbhum, Jharkhand,
      India. MATERIALS AND METHODS: The naturally occurring radioisotopes of uranium,
      U(nat), consisting of (234)U, (235)U and (238)U; (226)Ra, (230)Th and (210)Po
      were analysed in the fish samples from the surface water of Bagjata and
      Banduhurang mining areas after acid digestion. The ingestion dose, concentration
      factor and excess lifetime cancer risk of the radionuclides were estimated.
      RESULTS: The geometric mean activity of U(nat), (226)Ra, (230)Th and (210)Po in
      the fish samples was found to be 0.05, 0.19, 0.29 and 0.95 Bq kg(-1)(fresh)
      (Becquerel per kilogram fresh fish), respectively, in the Bagjata mining area,
      while for Banduhurang mining area it was estimated to be 0.08, 0.41, 0.22 and
      2.48 Bq kg(-1)(fresh), respectively. The ingestion dose was computed to be 1.88
      and 4.16 MUSvY(-1), respectively, for both the areas which is much below the 1
      mSv limit set in the new International Commission on Radiological Protection
      (ICRP) recommendations. The estimation of the Concentration Factors (CF) reveal
      that the CF from water is greater than 1 l/kg(-1)in most of the cases while from
      sediment CF is less than 1. The excess individual lifetime cancer risk due to the
      consumption of fish was calculated to be 2.53 * 10(-5) and 6.48 * 10(-5),
      respectively, for Bagjata and Banduhurang areas, which is within the acceptable
      excess individual lifetime cancer risk value of 1 * 10(-4). CONCLUSION: The study
      confirms that current levels of radioactivity do not pose a significant
      radiological risk to freshwater fish consumers.

PMID- 20670111
TI  - Inter-chromosomal variation in aberration frequencies in human lymphocytes
      exposed to charged particles of LET between 0.5 and 55 keV/MUm.
AB  - PURPOSE: To investigate the distribution of chromosomal aberrations in
      chromosomes 2, 8 and 14 induced by charged particles, using the fluorescence in
      situ hybridisation (FISH) technique. METHODS: Irradiation of peripheral blood
      from six healthy volunteers (four male and two female) was performed at the
      accelerators of the Joint Institute for Nuclear Research (JINR) in Dubna
      (Russia). Whole blood samples were irradiated with 2 and 3 Gy of protons (170
      MeV/nucleon (n), linear energy transfer (LET) ~ 0.5 keV/MUm), 3.5 Gy of (12)C
      ions (480 MeV/n, LET = 10.6 keV/MUm), 3 Gy of (12)C ions 500 MeV/n, LET = 12
      keV/MUm), 4 Gy of (7)Li ions (30 MeV/n, LET ~ 20 keV/MUm) and 3 Gy of (11)B ions
      (32 MeV/n, LET ~ 55 keV/MUm). Chromosomal aberrations were analysed in metaphase
      and prematurely condensed chromosomes (PCC) induced in G(2)-cells using calyculin
      A. Chromosomes 2, 8 and 14 were painted in different colours and aberrations
      scored with the help of an image-analysis system. RESULTS: Chromosome 2 was
      generally less sensitive than expected on the basis of its DNA content. A higher
      than expected frequency of exchanges was found in chromosomes 8 and 14. On
      average, the dicentric frequency in chromosome 2 was higher than the
      translocation frequency, whereas variable dicentric to translocation ratios were
      observed in chromosomes 8 and 14. When aberrations in all painted chromosomes
      were summed up the ratio was close to 1. The frequency of complex aberrations
      correlated with LET. CONCLUSION: In lymphocytes of donors studied in this work
      chromosome 2 appears to be consistently less sensitive to protons and heavy ions
      than chromosomes 8 and 14. Complex aberrations appear to be a potential marker of
      radiation quality.

PMID- 20670112
TI  - Induction of adaptive response in Drosophila after exposure to low doses of UVB.
AB  - PURPOSE: The aim of this study was to assess the adaptive response induced by low
      doses of ultraviolet-B (UVB, 290-320 nm) radiation in the Drosophila wing spot
      test. MATERIALS AND METHODS: The adaptive response of Drosophila larvae to UVB
      light was studied by using a somatic mutation and recombination test (SMART). The
      SMART system used was the wing spot test, which uses morphological markers of the
      wing blade. This in vivo test has shown to be very useful to study the induction
      of genetic damage in somatic cells, measuring loss of heterozygosity (LOH)
      resulting from gene mutation, mitotic recombination, chromosomal rearrangements
      or chromosome loss. RESULTS: To determine the induction of adaptive response, two
      day-old Drosophila larvae were first irritated with an adaptive dose (58.3
      J/m(2)), followed by different challenge doses (178, 224, 288, 338, and 386
      J/m(2)). When the results obtained in the different challenge doses were compared
      with those obtained following the application of adaptive plus challenge doses,
      significant decreases (74.7-80.8%) in a first experiment, and (65.6-78.4%) in a
      second experiment, were observed in the frequency of mutant spots on the wing
      blades. CONCLUSIONS: Our results show that in Drosophila the adaptive response
      can be stimulated in vivo by UVB exposure.

PMID- 20670113
TI  - Human papillomavirus 16 E6 increases the radiosensitivity of p53-mutated cervical
      cancer cells, associated with up-regulation of aurora A.
AB  - PURPOSE: To examine the effect of the human papillomavirus (HPV) type 16-E6 (HPV
      'early' gene) oncoprotein on in vitro radiosensitivity of HPV-negative/p53 mutant
      C33a cervical cancer cells. METHODS AND MATERIALS: The human cervical cancer cell
      line C33a was stably transfected with either the HPV16 E6 cDNA cloned into the
      vector pcDNA3.0 (C33aE6) or the empty-vector control (C33aV). Radiosensitivity,
      DNA damage, and cell cycle measurements were made using standard clonogenic
      assays, immunofluorescent assessment of nuclear histone H2AX phosphorylated on
      serine-139 (gamma-H2AX) foci, and flow cytometry. Western immunoblotting and
      fluorescence confocal microscopy were used to analyse the changes in cellular
      proteins. Real-time polymerase chain reaction (PCR) was used to compare levels of
      aurora A mRNA. RESULTS: Compared to C33aV cells, C33aE6 cells showed enhanced
      radiation cell killing. This was associated with a large amount of polyploidy
      which was followed by late cell death in C33aE6 cells. Aurora A was highly
      expressed in C33aE6 cells at pre- and post-irradiation times compared to C33aV
      cells. Silencing aurora A resulted in a reduced amount of residual gamma-H2AX
      foci in C33aE6 cells, and diminished the difference in radiosensitivity between
      the C33aE6 and C33aV cells. CONCLUSION: Our in vitro results indicate that
      genetic instability could be augmented in the HPV-infected cancer cells by up
      regulation of aurora A, especially against a background of dysfunctional p53.
      Further studies are needed to examine whether aurora A could be a viable
      therapeutic target in HPV-related tumours.

PMID- 20670115
TI  - High-titer GAD65 autoantibodies detected in adult diabetes patients using a high
      efficiency expression vector and cold GAD65 displacement.
AB  - Adult type 2 diabetes patients with GAD65 autoantibodies (GADA) are known as
      latent autoimmune diabetes in adults (LADA). It has been suggested that GADA in
      LADA patients preferentially bind to the N-terminal end of GAD65. Using the N
      terminal end extension of 35S-GAD65 generated by the pEx9 plasmid, we tested the
      hypothesis that GADA in LADA patients preferentially react with 35S-GAD65 from
      the pEx9 plasmid compared to the normal length pThGAD65 plasmid. Healthy control
      subjects (n = 250) were compared with type 1 (n = 23), type 2 (n = 290), and
      unspecified (n = 57) diabetes patients. In addition, radio-binding assays for
      GADA with 35S-GAD65 generated from both the pEx9 and pThGAD65 plasmids were used
      in displacement assays with an excess of recombinant human GAD65 (2 MUg/mL) to
      correct for non-specific binding. 35S-GAD65 produced by either pEx9 or pThGAD65
      did not differ in binding among the healthy controls and among the type 1
      diabetes patients. Among the type 2 and unspecified patients, there were 4/290
      and 3/57 patients, respectively, with binding to the pEx9 but not to the pThGAD65
      generated 35S-GAD65. In the displacement assay, we discovered 14 patients with
      very high-titer GADA among the type 1 (n = 3, 12,272-29,915 U/mL), type 2 (n = 7;
      12,398-334,288 U/mL), and unspecified (n = 4; 20,773-4,053,580 U/mL) patients.
      All samples were fully displaced following appropriate dilution. We conclude that
      pThGAD65 is preferred for the coupled in vitro transcription translation of 35S
      GAD65 and that displacement with recombinant GAD65 may detect very high-titer
      GADA with possible clinical relevance.

PMID- 20670116
TI  - The regulatory role of dendritic cells in the induction and maintenance of T-cell
      tolerance.
AB  - The induction and maintenance of T-cell tolerance to tissue antigens is essential
      to prevent autoimmunity. Combinations of central and peripheral mechanisms act in
      parallel to inactivated, eliminated or control autoreactive T cells. Both
      centrally and peripherally, a key requirement for self-tolerance is the
      presentation of self-antigens in a correct context. There is now evidence to
      suggest that dendritic cells (DCs) play a fundamental role in the development of
      central and peripheral tolerance. In this review, we summarize recent progress
      toward the definition of the multiple roles of DCs in these processes. We will
      also discuss the association between defects in the DC compartment and the
      development of autoimmune responses, with particular reference to DC deregulation
      in the context of type I diabetes.

PMID- 20670117
TI  - Epitopes, immunoglobulin classes and immunoglobulin G subclasses of calsequestrin
      antibodies in patients with thyroid eye disease.
AB  - A number of serum autoantibodies are associated with thyroid eye disease (TED),
      including those reactive against the calcium binding protein calsequestrin
      (CASQ). There are two isoforms of CASQ namely; CASQ1, found in skeletal,
      including extra ocular, muscle, and CASQ2, found in cardiac muscle. We determined
      (i) the reactivity profiles of CASQ1 and CASQ2 antibodies and (ii) the
      immunoglobulin (Ig) classes and IgG subclasses of CASQ1 antibodies, using enzyme
      linked immunosorbent assay. Of the 20 patients with TED tested, 35% were positive
      for CASQ1 antibodies, 25% for CASQ2 antibodies and two patients (10%) were
      positive for both antibodies. Of the 12 patients with Hashimoto's thyroiditis and
      ophthalmopathy tested, 25% were positive for CASQ1 antibodies, 42% for CASQ2
      antibodies and two patients (17%) were positive for both antibodies. CASQ1
      antibodies were mainly of the IgG class and IgG1 and IgG3 subclasses. These
      results suggest that CASQ1 and CASQ2 do not share major epitopes. Because
      antibodies of the IgG1 and IgG3 subclasses are cytotoxic, CASQ1 antibodies may
      contribute to the eye muscle damage in patients with TED. Because CASQ1
      antibodies were positive in only a third of patients with active TED we are
      unable to draw conclusions about their role in its pathogenesis. On the other
      hand, a possible role of CASQ2 antibodies in the aetiology of the cardiac
      complications of Graves' disease is a new avenue for research and appears worthy
      of further investigation.

PMID- 20670118
TI  - CD8(+) T regulatory/suppressor cells and their relationships with autoreactivity
      and autoimmunity.
AB  - Regulatory T lymphocytes (Treg) are fundamental for immune homeostasis since they
      contribute to the induction of peripheral tolerance to autologous antigens and
      regulate effector immune responses. Treg subsets are present within both the
      CD4+and the CD8(+) T cell compartments. Considering the CD8(+) Treg, in the last
      decades several subpopulations, provided with different phenotypes and mechanisms
      of action, have been characterized. This review is an attempt of integrating in
      an organic scenario the different CD8(+) Treg subpopulations. Moreover, it
      summarizes the findings so far achieved on the existence of CD8(+) Treg
      alterations in autoimmune diseases.

PMID- 20670120
TI  - Distinct role of T helper Type 17 immune response for Graves' hyperthyroidism in
      mice with different genetic backgrounds.
AB  - T helper type 17 (Th17) cells, a newly identified effector T-cell subset, have
      recently been shown to play a role in numerous autoimmune diseases, including
      iodine-induced autoimmune thyroiditis in non-obese diabetic (NOD)-H2(h4) mice,
      which had previously been thought Th1-dominant. We here studied the role of Th17
      in Graves' hyperthyroidism, another thyroid-specific autoimmune disease, in a
      mouse model. Two genetically distinct BALB/c and NOD-H2(h4) strains with intact
      or disrupted IL-17 genes (IL-17(+/+) or IL-17(-/-)) were immunized with
      adenovirus (Ad) expressing the thyrotropin receptor (TSHR) A-subunit (Ad
      TSHR289). Both IL-17(+/+) and IL-17(-/-) mice developed anti-TSHR antibodies and
      hyperthyroidism at equally high frequencies on the BALB/c genetic background. In
      contrast, some IL-17(+/+), but none of IL-17(-/-), mice became hyperthyroid on
      the NOD-H2(h4) genetic background, indicating the crucial role of IL-17 for
      development of Graves' hyperthyroidism in non-susceptible NOD-H2(h4), but not in
      susceptible BALB/c mice. In the T-cell recall assay, splenocytes and lymphocytes
      from the draining lymph nodes from either mouse strains, irrespective of IL-17
      gene status, produced IFN-gamma and IL-10 but not other cytokines including IL-17
      in response to TSHR antigen. Thus, the functional significance of Th17 may not
      necessarily be predictable from cytokine expression patterns in splenocytes or
      inflammatory lesions. In conclusion, this is, to our knowledge, the first report
      showing that the role of Th17 cells for the pathogenesis of a certain autoimmune
      disease depends on the mouse genetic backgrounds.

PMID- 20670119
TI  - Therapeutic potential of TGF-beta-induced CD4(+) Foxp3(+) regulatory T cells in
      autoimmune diseases.
AB  - Foxp3(+) T regulatory cell (Treg) subsets play a crucial role in the maintenance
      of immune homeostasis against self-antigens. The lack or dysfunction of these
      cells contributes to the pathogenesis and development of many autoimmune
      diseases. Therefore, manipulation of these cells may provide a novel therapeutic
      approach to treat autoimmune diseases. In this review, we provide current
      opinions concerning the classification, developmental, and functional
      characterization of Treg subsets. Particular emphasis will be focused on the
      therapeutic role of TGF-beta-induced CD4M(+) Foxp3(+) cells (iTregs) in
      established autoimmune disease. Moreover, the similarity and diversity of iTregs
      and naturally occurring, thymus-derived CD4(+) CD25(+) Foxp3(+) regulatory T
      cells (nTregs) will be discussed, including the finding that the pro-inflammatory
      cytokine IL-6 can convert nTregs to IL-17-producing cells, whereas iTregs induced
      by TGF-beta are resistant to the effects of this cytokine. Understanding these
      aspects may help to determine how Tregs can be used in the treatment of
      autoimmune diseases.

PMID- 20670121
TI  - Regulatory immune cell subsets in autoimmunity.
AB  - The immune system is equipped with different checkpoints that ensure the
      maintenance of immune tolerance to self-antigens and the prevention of
      autoimmunity. One mechanism of peripheral tolerance involves the activity of
      specialized subsets of immune cells that are capable to regulate and/or suppress
      pro-inflammatory immune responses. These regulatory cells include multiple
      subsets that belong to both the adaptive and innate immune systems. This issue of
      Autoimmunity describes the role of the different types of immunoregulatory cells
      in autoimmune diseases.

PMID- 20670122
TI  - Effect of shark cartilage derived protein on the NK cells activity.
AB  - CONTEXT: Shark cartilage has been used for its beneficial effects on various
      diseases. There are evidences, that shark cartilage stimulates cellular and
      humoral immune responses, which makes it an anti-tumor and immunomodulator
      candidate. OBJECTIVE: The immunostimulatory effect of shark cartilage derived
      proteins on the cytotoxic activity of natural killer (NK) cells from healthy
      human peripheral blood mononuclear cells was studied. MATERIAL AND METHODS: The
      shark cartilage was extracted and its bioactive proteins were purified using ion
      exchange chromatography (DE-52) and sequential fractionation on Amicon
      ultrafiltration membranes. The effect of each protein fraction on the modulation
      of cytotoxic activity of NK cells, as effectors, against K562, as target cells,
      was assayed by enzymatic lactate dehydrogenase test. RESULTS: The most
      immunostimulatory effect on the cytotoxic activity of NK cells was observed for
      AR10 fraction, containing proteins with molecular weight of about 14.5 kDa on the
      reducible discontinuous sodium dodecyl sulfate polyacrylamide gel
      electrophoresis. DISCUSSION: Among the examined shark cartilage derived proteins,
      the most immunostimulatory effects on the NK cells cytotoxicity was found for
      AR10 fraction with molecular weight of about 14 kDa. We propose-the direct
      interactions of shark cartilage derived proteins with NK cells surface receptors
      may lead to the enhancing in the cytotoxic activity of NK cells. CONCLUSION: Thus
      AR10 fraction, proteins of about 14.5 kDa, has a novel immunostimulatory effect
      on the NK cells activity in vitro and if confirmed by in vivo trials, it may lead
      to its future clinical applications as, immunotherapy of cancer, HIV, and
      augmentation of host immune system related immunodeficiency disorders.

PMID- 20670123
TI  - Leaf extracts from Phlomis crinita Cav. subs. mauritanica Munby affect immune
      cell functions in vitro.
AB  - Aqueous and methanolic leaf extracts from Phlomis crinita subs. mauritanica Munby
      were investigated for their potential immunomodulatory activity on mouse
      lymphocytes and macrophages in vitro. The phagocytic activity of macrophages and
      the proliferation of lymphocytes in the absence and presence of mitogens
      (lipopolysaccharide, LPS or lectin) were assayed. Depending on the
      concentrations, the extracts affect macrophage functions by modulating their
      lysosomal enzyme activity and nitric oxide release. For lymphocyte proliferation
      assay, both extracts enhance significantly cell proliferation either with or
      without mitogen stimulation. These results suggest that leaf extracts from P.
      crinita subs. mauritanica Munby contain potent components such as flavonoids that
      potentially may be useful for modulating immune cell functions in physiological
      and pathological conditions.

PMID- 20670125
TI  - "Hemolysis"--toward clearer terminology.

PMID- 20670127
TI  - Hydrogen sulfide exposure as a cause of sudden occupational death.

PMID- 20670128
TI  - UroVysion, urine cytology, and the College of American Pathologists: where should
      we go from here?
AB  - Abstract UroVysion (Abbott Molecular Inc, Des Plaines, Illinois) is a US Food and
      Drug Administration-approved test for the diagnosis of urothelial carcinoma.
      Although widely used, there are a variety of different ways to evaluate and
      interpret the test, and questions remain about the test's cost effectiveness and
      reproducibility in actual clinical practice. I suggest that the College of
      American Pathologists has a unique opportunity to create educational programs
      focusing on borderline or difficult urine cytology and UroVysion samples to
      provide data upon which to make evidence-based decisions concerning the best use
      of these tests.

PMID- 20670129
TI  - Blood bank safety practices: mislabeled samples and wrong blood in tube--a Q
      Probes analysis of 122 clinical laboratories.
AB  - CONTEXT: Although a rare occurrence, ABO incompatible transfusions can cause
      patient morbidity and mortality. Up to 20% of all mistransfusions are traced to
      patient misidentification and/or sample mislabeling errors that occur before a
      sample arrives in the laboratory. Laboratories play a significant role in
      preventing mistransfusion by identifying wrong blood in tube and rejecting
      mislabeled samples. OBJECTIVES: To determine the rates of mislabeled samples and
      wrong blood in tube for samples submitted for ABO typing and to survey patient
      identification and sample labeling practices and sample acceptance policies for
      ABO typing samples across a variety of US institutions. DESIGN: One hundred
      twenty-two institutions prospectively reviewed inpatient and outpatient samples
      submitted for ABO typing for 30 days. Labeling error rates were calculated for
      each participant and tested for associations with institutional demographic and
      practice variable information. Wrong-blood-in-tube rates were calculated for the
      30-day period and for a retrospective 12-month period. A concurrent survey
      collected institution-specific sample labeling requirements and institutional
      policies regarding the fate of mislabeled samples. RESULTS: For all institutions
      combined, the aggregate mislabeled sample rate was 1.12%. The annual and 30-day
      wrong-blood-in-tube aggregate rates were both 0.04%. Patient first name, last
      name, and unique identification number were required on the sample by more than
      90% of participating institutions; however, other requirements varied more
      widely. CONCLUSIONS: The rates of mislabeled samples and wrong blood in tube for
      US participants in this study were comparable to those reported for most European
      countries. The survey of patient identification and sample labeling practices and
      sample acceptance policies for ABO typing samples revealed both practice
      uniformity and variability as well as significant opportunity for improvement.

PMID- 20670130
TI  - Comparison of ThinPrep preparations to other preparation types in
      gastrointestinal cytology: observations from the College of American Pathologists
      Interlaboratory Comparison Program in Nongynecologic Cytology.
AB  - CONTEXT: Differences in participant responses for ThinPrep (TP) and non-ThinPrep
      (NTP) preparations for gastrointestinal cytology challenges, which circulated in
      the College of American Pathologists Interlaboratory Comparison Program in
      Nongynecologic Cytology (CAP NGC), may help to identify performance variations
      between preparation types. OBJECTIVE: To compare the performance of TP-prepared
      slides of gastrointestinal exfoliative cytology specimens to that of NTP
      preparations in the CAP NGC program. DESIGN: Participant responses between 2000
      and 2007 were evaluated for esophageal wash/brush, gastric wash/brush, and
      biliary tract brush specimens with a reference diagnosis of adenocarcinoma,
      squamous cell carcinoma, carcinoid, or spindle cell neoplasm. ThinPrep challenges
      were compared with NTP preparations (conventional smears, cytospins) for
      discordant responses. RESULTS: In all, 6023 pathologist responses and 3825
      cytotechnologist responses were reviewed. Non-ThinPrep preparations comprised 93%
      (n = 11 588) of the challenges, while 7% (n = 912) were TP material. A match for
      a "positive/suspicious" diagnosis was seen in 88.5% of NTP and 95.9% of TP
      preparations (P < .001). These results were statistically significant when the
      specific reference diagnosis was adenocarcinoma (P < .001). Overall performance
      of cytotechnologists was not different from that of pathologists (89.2% versus
      89.0%; P = .75). Cytotechnologists had better performance for detecting squamous
      cell carcinoma (96.3% versus 92.6%; P < .001), while pathologists had better
      performance for detecting spindle cell neoplasm (79.7% versus 42.9%; P < .001).
      CONCLUSIONS: ThinPrep preparations performed significantly better than NTP
      preparations in gastrointestinal cytology specimens circulated in an
      interlaboratory comparison program. Performance varied by reference
      interpretation, with the best performance for the interpretation of
      adenocarcinoma. Cytotechnologists and pathologists performed at the same level
      overall, but with differences for the diagnosis of spindle cell neoplasm and
      squamous carcinoma.

PMID- 20670131
TI  - PAX-2 is a helpful marker for diagnosing metastatic renal cell carcinoma:
      comparison with the renal cell carcinoma marker antigen and kidney-specific
      cadherin.
AB  - CONTEXT: The diagnosis of metastatic renal cell carcinoma (RCC) remains
      problematic. OBJECTIVE: To evaluate the role of PAX-2, a renal tubular cell
      transcription factor, in the diagnosis of metastatic RCC. PAX-2 expression in
      metastatic RCC was compared with that of the renal cell carcinoma marker antigen
      (RCCM) and kidney-specific cadherin (KSC), which are 2 known markers for RCC.
      DESIGN: Immunostaining for PAX-2, RCCM, and KSC was performed on consecutive
      tissue sections of 95 metastatic RCCs (77 clear cell, 8 papillary, 5 sarcomatoid,
      and 5 collecting duct) and 183 metastatic tumors other than RCC. RESULTS: For PAX
      2, positive immunoreactivity was detected in 77% clear cell, 75% papillary, 100%
      collecting duct, and 0% sarcomatoid metastatic RCCs. For RCCM, positive
      immunoreactivity was detected in 49% clear cell, 75% papillary, 0% collecting
      duct, and 0% sarcomatoid metastatic RCCs. For KSC, only 2 metastatic clear cell
      RCCs (3%) were positive. In combination, all markers were positive in 0% of
      cases; all markers were negative in 23% of cases (17 clear cell, 1 papillary, and
      for all 5 sarcomatoid); and at least 1 marker was positive in 76% of cases (PAX-2
      only in 28% of cases [21 clear cell, 1 papillary, and 5 collecting duct] and RCCM
      only in 3% of cases [2 clear, 1 papillary]). Of 183 metastatic tumors other than
      RCC, 14 were positive for PAX-2 (nodal metastasis of carcinoma of colon [1],
      breast [1], endometrium [1], and ovary [1]; and omental metastasis of carcinoma
      of uterus or ovary [10]). CONCLUSIONS: PAX-2 is a sensitive and specific marker
      for metastatic RCC. The diagnostic yield would be marginally increased by adding
      RCCM, but not KSC, as an immunomarker.

PMID- 20670132
TI  - Significance of high-risk human papillomavirus DNA detection in women 50 years
      and older with squamous cell papanicolaou test abnormalities.
AB  - CONTEXT: Data on cytologic screening and follow-up disproportionately reflect
      findings from frequently screened younger women, and data from screened women 50
      years and older using newer screening technologies remain limited. OBJECTIVE: To
      better understand the utility of adjunctive high-risk human papillomavirus
      (hrHPV) testing for disease risk stratification in women 50 years and older with
      a range of liquid-based cytology, abnormal, squamous cell Papanicolaou test
      results. DESIGN: Liquid-based cytology cases interpreted as high-grade squamous
      intraepithelial lesion (HSIL); low-grade squamous intraepithelial lesion (LSIL);
      atypical squamous cells, cannot exclude high-grade squamous intraepithelial
      lesion (ASC-H); and atypical squamous cells of undetermined significance (ASC-US)
      at Magee-Womens Hospital (Pittsburgh, Pennsylvania) were retrospectively
      identified for a 36-month period between July 1, 2005, and June 30, 2008, from
      women 50 years and older who also had hrHPV DNA test results. Histopathologic
      follow-up diagnoses were analyzed. RESULTS: During the study period, 4855 women
      50 years and older had HSIL, LSIL, ASC-H, or ASC-US Papanicolaou test results and
      hrHPV testing. In 89.3% of HSIL cases, 71.0% of LSIL cases, 38.9% of ASC-H cases,
      and 14.2% of ASC-US cases, hrHPV test results were positive. The positive
      predictive value of a positive hrHPV test for histopathologic cervical
      intraepithelial neoplasia 2/3(+) detection was 90.5% with HSIL, 15% with ASC-H,
      9.8% with LSIL, and 3.2% with ASC-US. A negative hrHPV test result had a 100%
      negative predictive value for histopathologic cervical intraepithelial neoplasia
      2/3(+) in both LSIL and ASC-H cases. CONCLUSIONS: In women 50 years and older, a
      positive hrHPV test result significantly increased the likelihood of follow-up
      histopathologic diagnoses of cervical intraepithelial neoplasia 2 /3(+) in
      patients with HSIL, LSIL, and ASC-H Papanicolaou test results compared with women
      with negative hrHPV test results. No cervical intraepithelial neoplasia 2/3(+)
      diagnoses were documented in women 50 years and older with LSIL or ASC-H
      Papanicolaou test results and negative hrHPV test results.

PMID- 20670133
TI  - Production and activation of matrix metalloproteinase 7 (matrilysin 1) in the
      lungs of patients with idiopathic pulmonary fibrosis.
AB  - CONTEXT: Idiopathic pulmonary fibrosis (IPF) is characterized by diffuse
      interstitial inflammation and fibroblast proliferation with accelerated
      remodeling of extracellular matrix, which result in irreversible destruction of
      the lung's architecture. OBJECTIVE: To elucidate the production levels, tissue
      localization, and activation of matrix metalloproteinase 7 (MMP-7) in the lungs
      of patients with IPF. DESIGN: Bronchoalveolar lavage analysis was performed in 17
      IPF patients and 6 healthy volunteers. Levels of MMP-7 in blood were assayed in
      23 IPF patients and 20 controls. Histologic and immunohistochemical analyses were
      performed on paraffin sections of the lung tissues from patients with IPF,
      interstitial pneumonia associated with rheumatoid arthritis, or nonspecific
      interstitial pneumonia. RESULTS: The proMMP-7 levels in bronchoalveolar lavage
      fluids from IPF patients were significantly higher than those from healthy
      controls, although there was no difference in the serum levels between the 2
      groups. By immunohistochemistry, proMMP-7 was localized mainly to the
      hyperplastic alveolar and metaplastic bronchiolar epithelial cells in the lung
      tissues from IPF patients. Active MMP-7 was immunolocalized on alveolar
      macrophages and hyperplastic epithelial cells, which were also immunostained with
      antibody against CD151, a molecule associated with activation of proMMP-7.
      Immunoblot analysis indicated the overproduction of proMMP-7 together with a
      small amount of active MMP-7 in bronchoalveolar lavage fluids from IPF patients.
      The MMP-7 activity was detected in a cross-linked carboxymethylated transferrin
      film assay. CONCLUSIONS: proMMP-7 is excessively produced by hyperplastic
      alveolar and metaplastic bronchiolar epithelial cells and activated locally in
      the lungs of IPF patients, suggesting that MMP-7 may contribute to the pathology
      of IPF.

PMID- 20670134
TI  - FLT3 mutations at diagnosis and relapse in acute myeloid leukemia: cytogenetic
      and pathologic correlations, including cuplike blast morphology.
AB  - CONTEXT: Acquired mutations in the fms-like tyrosine kinase 3 gene (FLT3)
      adversely impact relapse risk after chemotherapy in patients with acute myeloid
      leukemia (AML). The FLT3 mutation status may differ at diagnosis and relapse,
      suggesting a potential role in chemoresistance, yet few reports have addressed
      the cytogenetic and pathologic correlates of FLT3 mutations in relapsed AML.
      OBJECTIVES: To determine FLT3 mutations at diagnosis and relapse in a cohort of
      adult patients with chemoresistant AML and to correlate mutation status with
      multiple variables. DESIGN: We retrospectively determined FLT3 internal tandem
      duplication (FLT3/ITD) and FLT3 tyrosine kinase domain mutations in 50
      diagnosis/relapse pairs. We correlated FLT3 status with karyotype, World Health
      Organization 2008 subtype, white blood cell count, biopsy cellularity, blast
      percentage, and the presence of invaginated ("cuplike") blast nuclei. RESULTS: In
      11 of 50 patients (22%) the FLT3 mutation status differed at relapse and
      diagnosis, with a trend toward gain of FLT3/ITD (n = 7) and loss of FLT3 tyrosine
      kinase domain (n = 5) mutations. FLT3-mutated AMLs correlated with the World
      Health Organization 2008 subtype, AML, not otherwise specified,
      hyperproliferative features at diagnosis and relapse, and cytogenetic evolution.
      FLT3-wild type AMLs correlated with the subtype AML with myelodysplasia-related
      changes and frequently had adverse presentation karyotypes. Cuplike blast
      morphology was associated with FLT3/ITD+ status and with high mutation levels.
      Four of 7 patients with relapse-only FLT3/ITD mutations exhibited cuplike blasts
      at relapse after being noncuplike at diagnosis. CONCLUSIONS: In addition to well
      known correlates in pretreatment specimens, FLT3 mutation status has pathologic
      and cytogenetic significance at relapse. A shift to cuplike blast morphology at
      relapse may herald emergence of a previously undetected FLT3/ITD mutation.

PMID- 20670135
TI  - Challenges and opportunities in the adoption of College of American Pathologists
      checklists in electronic format: perspectives and experience of Reporting
      Pathology Protocols Project (RPP2) participant laboratories.
AB  - CONTEXT: The site-specific cancer checklists developed by the College of American
      Pathologists have the potential to improve the quality of data derived from
      pathology reports and incorporated into cancer registry databases and are now
      mandated report elements by various accrediting bodies. A pilot project, funded
      by the Centers for Disease Control National Project for Cancer Registries in
      2004, brought 4 pathology services in 3 states, with differing baseline
      implementations of the checklists, the opportunity to partner with their state
      National Project for Cancer Registry and their laboratory information system
      vendors to evaluate the feasibility of using electronically encoded College of
      American Pathologists cancer checklists for melanoma and tumors of the breast and
      prostate. OBJECTIVES: To identify existing and potential barriers to adoption of
      electronically encoded checklists and to also identify unique benefits not
      associated with text-only uses of the checklists. DESIGN: Participants mapped an
      implementation process from their current state to an electronic checklist
      capable state. For a sample of cases of melanoma, prostate, and breast cancers,
      the checklist elements were captured and transmitted to the registry using Health
      Level 7 (version 2.3.1). Process assessments with adoption of electronic
      checklists were conducted to assess pathologist effect and other potential
      barriers. An evaluation of the utility and usefulness of electronic checklists
      was performed after the project. RESULTS: All 4 laboratories successfully
      performed the capture of individual data elements from the College of American
      Pathologists checklist into a discrete format suitable for electronic
      transmission. The effect on pathologist performance and laboratory workflow was
      neutral. Points of resistance were identified in the checklists and in individual
      users. Specific challenges in individual laboratories varied according to the
      personnel and the baseline system in use. Clinical responses to implemented
      changes were generally positive. Analysis of the postproject experiences of the
      laboratories showed expansion of use and additional utility in some, but not all,
      laboratories. CONCLUSIONS: Pathology laboratory adoption of the College of
      American Pathologists cancer checklists in an electronic format suited to direct
      transmission to cancer registries poses business case, information technology,
      and human resource challenges. Laboratory information system vendor readiness to
      upgrade systems to facilitate this process helps to reduce some of these
      challenges. Personalities and preferences in practices may yet pose barriers to
      widespread adoption.

PMID- 20670136
TI  - Low-grade papillary urothelial carcinoma of the urinary bladder: a
      clinicopathologic analysis of a post-World Health Organization/International
      Society of Urological Pathology classification cohort from a single academic
      center.
AB  - CONTEXT: Few large cohort studies have addressed outcome in patients with
      noninvasive low-grade papillary urothelial carcinoma (LG-UrCa) following
      implementation of the 2004 World Health Organization/International Society of
      Urological Pathology (WHO/ISUP) consensus classification. OBJECTIVE: To evaluate
      our cohort of LG-UrCa cases classified according to 2004 WHO/ISUP to reassess
      outcome and interobserver agreement. DESIGN: Files were searched for all patients
      diagnosed with LG-UrCa between 1998 and 2008. All sections were reevaluated for
      accuracy of classification. RESULTS: A total of 112 cases initially diagnosed as
      LG-UrCa were identified. Of those, 8 of 55 cases (15%) initially diagnosed by
      nonurologic pathologists were reclassified as high-grade papillary urothelial
      carcinoma and were excluded. The mean length of follow-up was 40.1 months (range,
      2-113 months). Tumor recurrence was encountered in 56 of 104 patients (53.8%),
      including 37 (35.6%) with LG-UrCa or lower-grade tumors and 19 (18.3%) with high
      grade papillary urothelial carcinoma. Of the 19 patients demonstrating grade
      progression, 7 (37%) also developed stage progression (invasive carcinoma, n = 5;
      metastatic carcinoma, n = 2). Seven patients eventually underwent radical
      cystectomy. None of the 104 patients died of bladder cancer. The mean number of
      recurrence episodes was 3.11. The mean durations of time to first recurrence and
      time to grade progression were 13.9 months and 25.1 months, respectively. The
      mean size of initial tumors was 1.73 cm. There was no significant correlation
      between tumor size, patient age, sex, or smoking history and the likelihood for
      recurrence or grade progression. A significantly higher rate of recurrence was
      seen in patients with multiple tumors at initial diagnosis (P = .04).
      CONCLUSIONS: A tendency to underdiagnose high-grade papillary urothelial
      carcinoma continues to exist. More than half (53.8%) of patients with LG-UrCa
      developed recurrence, with an 18.3% incidence of grade progression and a 6.7%
      incidence of stage progression. Patients with multiple initial tumors had
      significantly higher risk of developing recurrence.

PMID- 20670137
TI  - Pathology economic model tool: a novel approach to workflow and budget cost
      analysis in an anatomic pathology laboratory.
AB  - CONTEXT: The need for higher efficiency, maximum quality, and faster turnaround
      time is a continuous focus for anatomic pathology laboratories and drives changes
      in work scheduling, instrumentation, and management control systems. OBJECTIVE:
      To determine the costs of generating routine, special, and immunohistochemical
      microscopic slides in a large, academic anatomic pathology laboratory using a top
      down approach. DESIGN: The Pathology Economic Model Tool was used to analyze
      workflow processes at The Nebraska Medical Center's anatomic pathology
      laboratory. Data from the analysis were used to generate complete cost estimates,
      which included not only materials, consumables, and instrumentation but also
      specific labor and overhead components for each of the laboratory's subareas. The
      cost data generated by the Pathology Economic Model Tool were compared with the
      cost estimates generated using relative value units. RESULTS: Despite the use of
      automated systems for different processes, the workflow in the laboratory was
      found to be relatively labor intensive. The effect of labor and overhead on per
      slide costs was significantly underestimated by traditional relative-value unit
      calculations when compared with the Pathology Economic Model Tool. Specific
      workflow defects with significant contributions to the cost per slide were
      identified. CONCLUSIONS: The cost of providing routine, special, and
      immunohistochemical slides may be significantly underestimated by traditional
      methods that rely on relative value units. Furthermore, a comprehensive analysis
      may identify specific workflow processes requiring improvement.

PMID- 20670138
TI  - The prognostic value of Ki-67, p53, epidermal growth factor receptor, 1p36, 9p21,
      10q23, and 17p13 in skull base chordomas.
AB  - CONTEXT: Skull base chordomas are rare, locally aggressive, notochord-derived
      neoplasms for which prognostically relevant biomarkers are not well established.
      OBJECTIVE: To evaluate whether newly discovered molecular alterations in
      chordomas have prognostic significance similar to what has been described
      regarding Ki-67 proliferation index. DESIGN: We conducted a retrospective study
      of 28 cases of primary clival chordomas. RESULTS: Ki-67 proliferation index 5% or
      more, p53 accumulation, and epidermal growth factor receptor expression were seen
      in 32%, 44%, and 8% of chordomas, respectively. 1p loss of heterozygosity (LOH)
      and/or 1p36 hemizygous deletion was seen in 30% of tumors, while 9p LOH and/or
      9p21 homozygous deletion was seen in 21% of cases. Loss of heterozygosity at
      10q23 and 17p13 were identified in 57% and 52% of cases, respectively. Ki-67
      proliferation index 5% or more and 9p LOH were significantly associated with a
      shorter overall survival, while homozygous deletion at 9p21 via fluorescence in
      situ hybridization approached significance. No correlation with survival was
      found for p53 or epidermal growth factor receptor expression, 1p36 hemizygous
      deletion, or LOH at 1p, 10q23, or 17p13. CONCLUSIONS: Chordomas with elevated Ki
      67 proliferation index or deletion at 9p21 may be at risk for a more aggressive
      clinical course and shorter survival. These biomarkers may thus be used to
      improve therapeutic stratification.

PMID- 20670139
TI  - Comparison of 10 indirect fluorescent antibodies to detect and type influenza A
      specimens.
AB  - CONTEXT: Management of influenza infections relies on rapid, accurate, and
      sensitive diagnostic techniques. Influenza A (IA) strain typing has become more
      important since the emergence of highly pathogenic avian and novel influenza
      strains and the high frequency of oseltamivir resistance in circulating H1N1
      isolates. OBJECTIVE: To analyze the performance of indirect fluorescent antibody
      testing for subtyping a broad range of IA strains. DESIGN: Ten indirect
      fluorescent antibody reagents were used to detect and type 100 archived IA
      respiratory specimens from 1986 through 1995 and 2006 through 2007 and a
      reassortant, nonpathogenic H5N1 sample. Both direct specimen and cultured
      isolates were tested. Reverse transcription-polymerase chain reaction was used to
      confirm indirect fluorescent antibody results. Three H1N1-, 2 H3N2-, and 1 H1-H2
      H3-H5-specific antibodies (Chemicon Diagnostics), an IA pool reagent (Trinity
      Biotech), and H1, H3, and H1-H3-specific antibodies (Centers for Disease Control
      and Prevention) were used. RESULTS: Reverse transcription-polymerase chain
      reaction confirmed all 100 isolates as IA and identified 71 as H1, 22 as H3, and
      7 as non-H1-H3. Sensitivity of direct specimen testing ranged was 18.3% to 57.7%
      for the H1 reagents, 36.4% to 50.0% for the H3 reagents, and 40.0% to 53.8% for
      the pool reagents. Subtyping was more sensitive on cultured isolates than direct
      specimens. Specificity for all antibodies was 89.7% to 100%. The H5N1 sample was
      positive by direct testing and culture (reverse transcription-polymerase chain
      reaction, Centers for Disease Control and Prevention H5N1 pool, Chemicon H1-H2-H3
      H5). No cross-reactivity was observed when the 10 antibodies were tested against
      other common respiratory viruses. CONCLUSIONS: When positive, IA subtyping
      antibodies can serve as a useful diagnostic tool when multiple influenza virus
      subtypes are cocirculating with different susceptibility patterns.

PMID- 20670140
TI  - Revisiting chordoma with brachyury, a "new age" marker: analysis of a validation
      study on 51 cases.
AB  - CONTEXT: Chordoma is a rare, notochordal tumor with a characteristic
      histomorphology and immunohistochemical profile. At times, it presents a
      diagnostic challenge, especially in small biopsies. Brachyury, a nuclear
      transcription factor, is a recently described immunohistochemical marker for
      diagnosing chordomas. OBJECTIVE: To study the sensitivity and specificity of
      brachyury in diagnosing chordomas by comparing its expression in axial chordomas
      with nonchordomatous tumors. DESIGN: Fifty-one axial chordomas, accessioned
      during a 10-year period, and 58 nonchordomatous tumors were subjected to
      brachyury staining by immunohistochemistry. RESULTS: The 51 chordomas occurred in
      36 men and 15 women. Sitewise, 34 cases (66.7%) occurred in the sacrococcyx, 9
      (17.6%) in the spine, and 8 (15.7%) in the skull base. Histologically, 34 cases
      (66.7%) were classical chordomas, 13 cases (25.5%) had a dominant chondroid
      component, and 2 cases each (3.9%) were chondroid chordomas and dedifferentiated
      chordomas, respectively. Brachyury staining was positive in 46 of the 51
      chordomas (90.2%) and negative in all 58 nonchordomatous tumors. The
      dedifferentiated area in 2 chordomas was negative for brachyury staining.
      Fourteen of 15 chordomas with chondroid component showed positive brachyury
      staining. Immunohistochemical expression of other markers, included cytokeratin
      (positive in 23 of 23 cases; 100%), epithelial membrane antigen (positive in 22
      of 22 cases; 100%) and S100 protein (positive in 18 of 21 cases; 85.7%).
      CONCLUSION: Exclusive brachyury expression in more than 90% of chordomas
      indicates its value as a unique, specific marker with other sensitive markers
      like cytokeratin, epithelial membrane antigen, and/or S100 protein in
      substantiating a diagnosis of chordoma, including on small biopsies.

PMID- 20670141
TI  - Interference of hawthorn on serum digoxin measurements by immunoassays and
      pharmacodynamic interaction with digoxin.
AB  - CONTEXT: Hawthorn is an herb indicated for treating cardiac illness. Because a
      patient taking digoxin may also take hawthorn, we investigated potential
      interference of hawthorn in serum digoxin measurements using immunoassays as well
      as pharmacodynamic interaction between hawthorn and digoxin. Hawthorn contains
      alkaloids that are structurally similar to digoxin and may interfere with serum
      digoxin measurement using immunoassays. In addition, hawthorn has cardioactive
      properties similar to digoxin. OBJECTIVE: To study potential pharmacodynamic
      interaction between hawthorn and digoxin. DESIGN: The effects of hawthorn extract
      on serum digoxin measurements using Digoxin III (Abbott Laboratories, Abbott
      Park, Illinois) and the Tina-Quant digoxin assay (Roche Diagnostics,
      Indianapolis, Indiana) were investigated using 2 different brands of extract. To
      study the pharmacodynamic interaction between hawthorn and digoxin, we used an
      isolated adult rat cardiomyocyte system, measuring calcium transients by real
      time fluorescence spectrophotometry. RESULTS: Hawthorn interfered only with the
      Digoxin III immunoassay but had no effect on the Tina-Quant assay. Both hawthorn
      extracts increased intracellular calcium levels, but the lack of additive
      response with digoxin suggests both may bind to the same site of Na, K adenosine
      triphosphatase. CONCLUSION: Because of interference of hawthorn with a digoxin
      immunoassay and pharmacodynamic interaction with digoxin, a patient receiving
      digoxin should avoid hawthorn.

PMID- 20670142
TI  - Hypomethylation of the DNMT3L promoter in ocular surface squamous neoplasia.
AB  - CONTEXT: Cancer is known to have epigenetic inputs, with events like genomewide
      hypomethylation and gene-specific hypermethylation of DNA. The DNA
      methyltransferase enzymes act as effectors of this reprogramming. A previous
      study revealed that hypomethylation at the DNA methyltransferase 3-like (DNMT3L)
      promoter could be a potential biomarker in cervical tumors. Because the
      pathobiology of ocular surface squamous neoplasia (OSSN) is similar to that of
      cervical tumors, we wanted to determine whether similar changes occur in the
      methylation pattern at the DNMT3L promoter in OSSN. OBJECTIVE: To evaluate the
      methylation status of the DNMT3L promoter in OSSN compared with healthy
      conjunctiva. DESIGN: We evaluated DNA methylation at the DNMT3L promoter in the
      tumor tissues of 6 patients with histologically proven OSSN and in healthy
      conjunctiva tissue from 7 individuals for controls using the sodium bisulfite
      assisted conversion of genomic DNA. Extracted genomic DNA was treated with sodium
      bisulfite and amplified with specific primers for the DNMT3L promoter region. The
      specific polymerase chain reaction products were cloned and sequenced. RESULTS:
      The mean age of these patients was 50.2 years (range, 35-65 years).
      Histologically, 4 OSSN cases were invasive; 2 were intraepithelial. Healthy
      conjunctival tissues exhibited a methylated promoter region, whereas a variable
      loss of methylation was observed in all 6 OSSN cases. CONCLUSIONS: We have, for
      the first time to our knowledge, identified loss of methylation at the DNMT3L
      promoter in OSSN cases, but its physiologic significance is yet to be understood.
      Further studies are warranted to substantiate our results.

PMID- 20670143
TI  - A practical approach to testicular biopsy interpretation for male infertility.
AB  - CONTEXT: The combination of testicular biopsy and clinical evaluation for male
      infertility is becoming progressively more important because new technologies
      allow men previously considered infertile to father children. Although most
      general pathologists are experienced with normal, neoplastic, and cryptorchid
      testicular specimens, the testicular biopsy for infertility requires
      understanding of a different set of diagnostic categories not otherwise commonly
      encountered. OBJECTIVE: To highlight a standardized nomenclature for germ cell
      abnormalities allowing for effective communication with the urologist and maximal
      clinical benefit from the biopsy. DATA SOURCES: Previously published consensus
      statements, review articles, peer-reviewed research publications, and abstracts.
      CONCLUSIONS: A practical approach to evaluating testicular biopsies for fertility
      and the clinical implications for each abnormality are herein outlined.

PMID- 20670144
TI  - Diagnostic pitfalls in syringocystadenocarcinoma papilliferum: case report and
      review of the literature.
AB  - We report the first case, to our knowledge, of syringocystadenocarcinoma
      papilliferum with p63-verified squamous differentiation and extensive dermal
      invasion accompanying in situ components. An 86-year-old woman presented with a
      neoplasm on the neck, and the intralesional heterogeneity typical of these
      neoplasms led to an initial diagnosis on needle biopsy favoring squamous cell
      carcinoma. Excision illustrated diverse morphology, raising a broad differential
      diagnosis, including more common extracutaneous malignancies, such as breast,
      gastrointestinal, and ovarian primary tumors. Fortuitous sectioning revealed a
      focal connection to the skin surface with evidence of apocrine differentiation
      allowing final diagnosis as syringocystadenocarcinoma papilliferum. Our
      literature review shows the histologic and immunohistochemical features of
      syringocystadenocarcinoma papilliferum are not well defined outside of their
      clear morphologic overlap with syringocystadenoma papilliferum. We describe our
      findings and diagnostic pitfalls to help pathologists encountering this unusual
      apocrine neoplasm.

PMID- 20670145
TI  - Solid variant of papillary renal cell carcinoma with spindle cell and tubular
      components.
AB  - The solid variant of papillary renal cell carcinoma, when strictly defined as a
      tumor in which no true papillae can be identified, is extremely rare, with only a
      few cases reported in the literature. This tumor is characterized histologically
      by solid sheets of cells without true papillae; nevertheless, immunohistochemical
      and genetic analysis supports the classification of this tumor as a variant of
      papillary renal cell carcinoma. We report a case of solid variant of papillary
      renal cell carcinoma affecting a young man and provide histologic and clinical
      follow-up data, adding an additional case of this extremely rare pathology to the
      literature. In addition, we describe the first case, to our knowledge, of a solid
      variant of papillary renal cell carcinoma to contain a high-grade (sarcomatoid)
      spindle cell component.

PMID- 20670146
TI  - Basaloid follicular hamartoma.
AB  - Basaloid follicular hamartoma is a benign lesion of important consideration
      because it can be mistaken both clinically and histologically for basal cell
      carcinoma. The formation of basaloid follicular hamartoma has been linked to a
      mutation in the patched gene, which is part of the same pathway implicated in
      nevoid basal cell carcinoma syndrome. While these hamartomas are considered
      benign lesions, malignant growths have been reported to arise within them, which
      raises the question, "Is basaloid follicular hamartoma a premalignant lesion?"
      Correct identification allows for periodic monitoring for malignant
      transformation, while sparing patients unnecessary surgery. Treatment strategies,
      including experimental therapies, are reviewed.

PMID- 20670147
TI  - Solid organ transplant-associated acute graft-versus-host disease.
AB  - Solid organ transplant-associated graft-versus-host disease is an infrequent and
      potentially lethal complication. The incidence of this complication varies
      according to the type of organ transplant with higher rates associated with liver
      and small bowel transplants. The clinical presentation typically includes fever
      and skin rash, and most cases quickly advance to become a multisystem disease
      affecting the bone marrow and other nontransplanted solid organs. The diagnosis
      is based on the clinical symptoms, pathologic changes in biopsied tissues, and
      systemic lymphoid chimerism. The mortality of this disease can exceed 75% after
      liver transplant and most patients die from infections or hemorrhage due to bone
      marrow failure. There is no standard treatment strategy for this complication,
      and the management mainly consists of both prophylaxis and immediate treatment
      without delay. This short review summarizes the current pathogenesis, diagnosis,
      and treatment of this entity.

PMID- 20670148
TI  - BRAF mutation testing in colorectal cancer.
AB  - Colorectal cancer is the second most common cause of cancer death in the United
      States. Understanding the biochemical pathways underlying carcinogenesis has
      paved the way for more effective treatments and better outcomes. BRAF mutation
      testing has a role in (1) differentiating sporadic colorectal cancer from Lynch
      syndrome, (2) identifying cancers lacking BRAF mutation that are more likely to
      respond to epidermal growth factor receptor inhibitor therapy, and (3) conferring
      worse prognosis in colorectal cancer that is microsatellite stable. Several
      analytic methods are available to reliably detect BRAF mutations. Real-time
      polymerase chain reaction identifies the most common BRAF mutation, V600E, in
      frozen or paraffin-embedded colorectal cancer tissue. Traditional DNA sequencing
      and the somewhat more-sensitive pyrosequencing method can detect multiple
      alternative BRAF mutations that are predicted to constitutively activate
      signaling through the MAPK pathway, promoting tumor growth and survival.
      Pathologists play an important role in assay validation as well as in consulting
      with clinicians about indications for testing, ensuring quality of testing, and
      interpreting results in conjunction with other clinicopathologic factors
      important in the management of affected patients.

PMID- 20670150
TI  - Elevated plasma chymotrypsin-like protease (chymase) activity in women with
      preeclampsia.
AB  - OBJECTIVE: Chymase, a chymotrypsin-like protease, is a non-ACE angiotensin II
      (Ang II) generating enzyme. We determined if maternal chymotrypsin-like
      protease/chymase activity was increased in women with preeclampsia (PE). METHODS:
      Maternal plasma was extracted from venous blood of healthy nonpregnant women,
      women with normal and preeclamptic pregnancies. Chymotrypsin-like
      protease/chymase activity was measured by a colorimetric assay. Maternal vessel
      chymotrypsin-like protease/chymase expression was examined by
      immunohistochemistry. RESULTS: Maternal plasma chymotrypsin-like protease/chymase
      activity was significantly higher in women with PE than in nonpregnant and normal
      pregnant women: 0.181 +/- 0.011 vs. 0.097 +/- 0.05 (p < 0.01) and 0.132 +/- 0.013
      (p < 0.05) microkat/mL. Chymotrypsin-like protease/chymase activity was markedly
      reduced 24 hours postpartum in women with PE, p < 0.05. Enhanced chymotrypsin
      like protease/chymase expression was observed in vascular endothelium in women
      with PE compared with those in normal pregnancies. CONCLUSIONS: Elevated maternal
      chymotrypsin-like protease/chymase activity and enhanced protease immunostaining
      in the maternal vessel endothelium may constitute the exacerbated inflammatory
      state and account for the increased vascular Ang II sensitivity in PE.

PMID- 20670151
TI  - Late onset preeclampsia is not an innocuous condition.
AB  - OBJECTIVE: To describe the profile and outcome of late-onset preeclampsia (LOPE).
      METHODS: Retrospective study of 264 singleton pregnancies presenting before
      delivery at two referral centres in South Africa. RESULTS: Primigravid patients
      constituted 56.8% of the group, while 57.6% were graded as severe. Median
      gestational age at diagnosis was 37 (34-43) weeks. 30.7% of patients experienced
      >or=1 major maternal complication including 34 (12.9%) cases of eclampsia. There
      were no maternal or early neonatal deaths. Five intrauterine deaths occurred, all
      due to placental abruption. The perinatal mortality rate was 18.9 per thousand
      births. CONCLUSIONS: Late-onset preeclampsia often presents as severe disease.

PMID- 20670152
TI  - Neurocognitive development of children following in-utero exposure to labetalol
      for maternal hypertension: a cohort study using a prospectively collected
      database.
AB  - OBJECTIVE: To identify the effect of prenatal labetalol exposure on children's
      long-term neurodevelopment. DESIGN: A cohort study with matched controls using a
      prospectively collected database. METHODS: Participants were women counseled for
      hypertension in pregnancy at the Motherisk Program at The Hospital for Sick
      Children, and The Sunnybrook Health Sciences Centre, Toronto, Canada and their
      children. Mother-child pairs were divided into groups based on in-utero exposure
      to labetalol (n = 32), non-teratogenic substances (n = 42), and methyldopa (n =
      25). The main outcome measures were children's Full-Scale IQ, Performance IQ and
      Verbal IQ assessed with the Wechsler Preschool and Primary Scale of Intelligence.
      RESULTS: There were no statistically significant differences in scores on Full
      Scale IQ, Performance IQ, or Verbal IQ between children exposed in utero to
      labetalol and to non-teratogenic substances (Full-Scale IQ: 109.60 +/- 8.20 vs.
      111.90 +/- 11.39, p = 0.647; Performance IQ: 104.80 +/- 8.69 vs. 110.19 +/-
      12.91, p = 0.186; Verbal IQ: 112.27 +/- 11.05 vs. 11.21 +/- 11.98, p = 0.922,
      respectively). Children in the methyldopa group achieved lower scores on measures
      of Full-Scale IQ and Performance IQ when compared to children exposed to non
      teratogenic substances (Full-Scale IQ: 105.24 +/- 12.46 vs. 111.90 +/- 11.39, p =
      0.043; Performance IQ: 98.80 +/- 16.16 vs. 110.19 +/- 12.91, p = 0.002,
      respectively). Linear regression analysis revealed that maternal Full Scale IQ
      was a significant predictor of children's Full-Scale IQ (p = 0.020, beta =
      0.229). Maternal Performance IQ and duration of treatment with methyldopa were
      significant predictors of children's Performance IQ (p = 0.028, beta = 0.232; p =
      0.16, beta = -0.255, respectively). CONCLUSION: In-utero exposure to labetalol
      does not appear to adversely affect the neurocognitive development of young
      children. These reassuring results may aid disease management for pregnant women
      with hypertension.

PMID- 20670153
TI  - Postpartum course of gestational hypertension and preeclampsia.
AB  - BACKGROUND: New onset hypertension (gestational hypertension and preeclampsia)
      complicates 6-8% of pregnancies and usually resolves postpartum, but the time to
      normalization of blood pressure (BP) in the postpartum period is not known.
      METHODS: We performed a retrospective cohort study of previously normotensive
      women who developed gestational hypertension or preeclampsia, and determined the
      number of weeks postpartum to BP normalization. RESULTS: 62 women with no history
      of hypertension prior to pregnancy were included, age 35.3 +/- 7.1 years.
      Hypertension developed at gestational age 15-40 weeks; 45% developed hypertension
      within 3 days of delivery, 52% developed hypertension 1-22 weeks prior to
      delivery, and 5% had onset only postpartum. Infants were born at gestational age
      35.15 +/- 4.7 weeks. Average BP at treatment initiation was 162/95 mm Hg.
      Preeclampsia and/or HELLP syndrome was diagnosed in 48%. Most were treated with
      BP medication in the puerperium. In those whose BP normalized, time to
      normalization was 5.4 +/- 3.7 weeks. Those who remained hypertensive beyond 6
      months (19%) were older (38.8 years vs. 34.4, p = 0.018). Three women had
      secondary hypertension; primary hyperaldosteronism was diagnosed in 2 women and
      renovascular hypertension in 1. CONCLUSION: Hypertension presenting in pregnancy
      normalized postpartum in 81% of this cohort, in most by 3 months. Those who
      remained hypertensive at 6 months postpartum tended to be older than patients
      whose BP normalized. Secondary hypertension was detected and surgically corrected
      in 3 patients. Further studies are needed to characterize those most likely to
      benefit from postpartum antihypertensive treatment and to guide management.

PMID- 20670154
TI  - Respiratory parameters and exercise functional capacity in preeclampsia.
AB  - OBJECTIVE: To evaluate maximal respiratory pressures, pulmonary volumes and
      capacities and exercise functional capacity in pregnant women with preeclampsia.
      METHOD: Primigravid women with preeclampsia and healthy primigravid women were
      evaluated by means of manovacuometry, spirometry and the 6-minute walk test.
      RESULTS: The group with preeclampsia showed higher minute ventilation and lower
      forced vital capacity and exercise tolerance. The presence of preeclampsia and
      forced vital capacity were predictors in the six-minute walk test. CONCLUSION:
      Preeclampsia showed significant alterations in the respiratory system and was
      associated with lower exercise tolerance; however, it did not affect respiratory
      muscle functions.

PMID- 20670155
TI  - Comparison of serum levels and the placental expression of resistin between
      patients with preeclampsia and normal pregnant women.
AB  - OBJECTIVE: The aim of this study was to evaluate serum resistin levels in women
      with preeclampsia compared to those in normal pregnant women and normal non
      pregnant women, and to examine placental resistin expression. METHODS: Serum
      resistin levels were measured by enzyme-linked immunosorbent assay and placental
      resistin expression was determined by immunohistochemistry. RESULTS: Serum
      resistin levels were significantly elevated in women with preeclampsia compared
      to normal pregnant women and non-pregnant women. There was no significant
      difference in placental resistin expression. CONCLUSION: The placenta may not be
      the origin of the resistin that contributes to increased serum levels in women
      with preeclampsia.

PMID- 20670156
TI  - Soluble endoglin for the prediction of preeclampsia in a high risk cohort.
AB  - OBJECTIVES: To evaluate soluble endoglin (sEng) and the soluble fms-like tyrosine
      kinase 1 (sFlt1) to placental growth factor (PlGF) ratio for the prediction of
      preeclampsia in high-risk women, and to evaluate differences in sEng between
      women with high-risk singleton and multiple gestation pregnancies. STUDY DESIGN:
      We collected serial serum specimens from 119 women at high preeclampsia risk.
      sEng, sFlt1 and PlGF were measured by ELISA. RESULTS: Among subjects who did not
      develop preeclampsia, mean serum sEng was significantly higher in those with
      multiple gestation pregnancies vs. high-risk singletons. Among women with
      singleton gestations, mean serum sEng was higher in subjects who developed early
      onset (<34 weeks) and late-onset (>or= 34 weeks) preeclampsia, as compared with
      subjects without preeclampsia, from 22 weeks and 28 weeks gestation onward,
      respectively. The within-woman rate of change of sEng was also higher in women
      who later developed preeclampsia. CONCLUSIONS: sEng is higher in women with
      multiple gestations vs. high-risk singleton pregnancies. In high-risk women,
      serum sEng is increased prior to preeclampsia onset.

PMID- 20670157
TI  - Risk factors for postpartum antihypertensive medication requirement in severe
      preeclampsia.
AB  - OBJECTIVE: To determine antepartum risk factors for postpartum antihypertensive
      medication use in women with severe preeclampsia. METHODS: A case control study
      was performed on patients who were diagnosed with severe preeclampsia between
      January 2000 and June 2004 at a single tertiary care center. Women discharged
      from the hospital on antihypertensive medications were compared to women
      discharged home on no antihypertensive medications. Demographic data, maternal
      medical conditions, and delivery data were abstracted from maternal charts. Risk
      factors were evaluated using multiple logistic regression. RESULTS: 218 patients
      with severe preeclampsia were identified, of which 112 were discharged on
      antihypertensives. After adjusting for confounding variables, chronic
      hypertension was associated with an increased need for post partum
      antihypertensive medication (OR 7.5 (95% CI 3.0-18.1)). A dose-dependent
      association was seen with intrapartum hydralazine administration. High-dose
      hydralazine was associated with increased need for postpartum antihypertensive
      mediation (OR 5.74 95% CI 2.03-16.2) compared to low-dose hydralazine (OR of 2.51
      95% CI 1.26-5.01). Hemolysis/Elevated liver function/low platelet (HELLP)
      syndrome was associated with a decreased need for antihypertensive medication (OR
      0.33, 95% CI 0.13-0.82). CONCLUSIONS: Patients with chronic hypertension and
      patients who required intrapartum hydralazine were more likely to require
      antihypertensive medications at discharge.

PMID- 20670158
TI  - Evaluation of automatic pointing assistive function effect in cursor-positioning
      task for people with disabilities.
AB  - PURPOSE: This study evaluates the cursor-positioning effect with the automatic
      pointing assistive programme (APAP) and a newly mouse driver for people with
      disabilities. METHOD: The APAP is designed to move the cursor to a target
      instantaneously when the cursor reaches inside this circular activation area. In
      this study, 20 people with disabilities participated in the experiment. Trial
      completion time was determined and compared with those in previous studies of
      cursor-capturing functions (jumping and gravity) and normal condition. RESULT:
      Experimental results reveal that the pointing efficiency was improved by 65.29%
      with the APAP compared to that of the normal condition (p < 0.001) for people
      with disabilities. Data were subjected to one-way analysis of variance (ANOVA),
      with the level of significance p <= 0.05 and the ANOVA indicates that the
      capturing functions had a significant effect on the trial completion time
      (F(2,57) = 199.21; p < 0.001). CONCLUSIONS: The performance of the APAP is
      superior to those in previous studies in positioning time for people with
      disabilities. The APAP function is expected to help aged users and novices in
      operating a mouse efficiently and easily.

PMID- 20670159
TI  - Budget impact model of tobramycin inhalation solution for treatment of
      Pseudomonas aeruginosa in cystic fibrosis patients.
AB  - BACKGROUND: Pseudomonas aeruginosa (PA) is the most common airway pathogen in
      cystic fibrosis (CF) patients. The objective of this analysis was to determine
      the costs of managing PA infection in CF patients with a chronic regimen of
      tobramycin inhalation solution (TIS). METHODS: A budget impact model of CF
      patients was developed to evaluate the costs of TIS from a US managed-care
      organization (MCO) perspective. The Microsoft Excel model compared TIS treatment
      plus standard care with standard care alone over a 4-year time horizon and
      included the cost of drugs, medical care, and annual probabilities of
      hospitalization and IV anti-pseudomonal (anti-PA) antibiotics administration.
      RESULTS: For an MCO with 5,000,000 members, 389 members 6 years of age or older
      were estimated to have CF, and 218 (56%) had PA infection. Assuming that use of
      TIS increased from 20% to 25%, the 1-year budget increased $231,251 or from
      $0.049 to $0.053 per member per month (PMPM). The net drug budget increase was
      $243,919, while medical costs associated with exacerbation management decreased
      $12,669 over the first year. Increasing utilization of TIS, from 20% to 40% over
      4 years resulted in an incremental overall budget increase of $925,002, a 3%
      decrease in hospitalizations, and a 4% decrease in administrations of IV anti-PA
      antibiotics. These reductions translated to a medical care cost saving of $50,676
      over 4 years. Limitations of this study include that the clinical data for the
      model are from clinical trials conducted in 1996 and the estimation of TIS use
      for CF patients with chronic PA infections can be impacted by TIS adherence.
      CONCLUSION: Model results suggest that increasing the use of TIS decreases
      medical care costs due to decreased hospital admissions and the use of IV anti-PA
      antibiotics at the expense of higher drug costs.

PMID- 20670160
TI  - Mesenchymal stem cells: a new promise in anticancer therapy.
AB  - Novel cell-based and gene therapies represent promising approaches for the
      treatment of incurable diseases, including cancer. Following the success of the
      hematopoietic stem cell-based transplantation, other populations of adult
      progenitor cells, including mesenchymal stem cells (MSCs), have been identified
      as powerful therapeutic tools in humans. The intrinsic capability of MSCs to
      migrate toward injured tissues emphasizes their suitability to deliver anticancer
      agents for new clinical applications in addition to the tissue repairing
      capacity. Here, we revisit the experimental history of MSCs, the most exciting
      features of their biology in keeping with their promising applications in cell
      based therapeutic strategies for cancer treatment.

PMID- 20670161
TI  - New promising Euphorbiaceae extracts with activity in human lymphocytes from
      primary cell cultures.
AB  - CONTEXT: Euphorbiaceae plants exhibit anti-inflammatory and immunomodulatory
      properties. METHODS: We evaluated the activity of 14 extracts from seven
      Euphorbiaceae plants on primary immune cell cultures from healthy individuals.
      Peripheral blood mononuclear cells (PBMC) were exposed to the extracts w/o
      phytohaemagglutinin A or cycloheximide as agents that induce proliferation or
      apoptosis in PBMC, respectively. RESULTS: We found that five up to 14
      Euphorbiaceae's extracts had the ability to modulate at least one of the immune
      parameters evaluated in this study. However, only the latex extracts of Euphorbia
      cotinifolia and Euphorbia tirucalli strongly induced both proliferation and
      apoptosis in PBMC. These extracts were further subfractioned by silica gel column
      chromatography. Two subfractions with enhanced activity in comparison to the
      crude extracts were obtained. Although these subfractions induced proliferation
      on both CD3(+) and CD3(-) cells, the most prominent effects were observed in the
      former subpopulation. Interestingly, the subfraction from E. tirucalli induced
      lymphocyte proliferation without the need of accessory cells; this ability was
      not inhibited by the carbohydrates d-galactose and alpha-Methyl-D
      Mannopyranoside. CONCLUSIONS: Altogether, these results reveal the presence of
      novel candidates within the Euphorbia plants to induce proliferation and
      apoptosis in human lymphocytes, mainly in CD3(+) T cells.

PMID- 20670162
TI  - Wnt signaling regulates Snai1 expression and cellular localization in the mouse
      intestinal epithelial stem cell niche.
AB  - Snail genes are transcriptional repressors well known to play important roles in
      epithelial to mesenchymal transitions during both embryogenesis and cancer
      metastasis. Although they are generally regarded as markers of mesenchymal cells,
      Snail genes have also recently been implicated in regulating stem cell
      populations in both Drosophila and vertebrates. In this study we investigate
      Snai1, a member of the mouse Snail family, in the intestinal stem cell niche and
      examine the relationship between canonical Wnt signaling, a key regulatory
      pathway of intestinal stem cells, and expression and cellular localization of
      Snai1. Strong nuclear expression of Snai1 was detected in the crypt base columnar
      stem cells in the adult small intestine while Snai1 was mostly found in the
      cytoplasm of differentiated enterocytes and enteroendocrine cells. Expression and
      cellular localization of Snai1 in the intestinal epithelium appears to be
      regulated by the canonical Wnt signaling pathway as Snai1 expression was
      dramatically reduced after conditional deletion of beta-catenin. Conversely,
      significant nuclear Snai1 was detected in polyps derived from Apc(min) mice and
      in intestinal villi after conditional mutation of Apc in AhCre, Apc(f/f) mice,
      indicating that upregulation of the Wnt pathway in the intestinal epithelium
      induces both increased expression and nuclear localization of Snai1.

PMID- 20670163
TI  - Effect of microRNA modulation on bioartificial muscle function.
AB  - Cellular therapies have recently employed the use of small RNA molecules,
      particularly microRNAs (miRNAs), to regulate various cellular processes that may
      be altered in disease states. In this study, we examined the effect of transient
      muscle-specific miRNA inhibition on the function of three-dimensional skeletal
      muscle cultures, or bioartificial muscles (BAMs). Skeletal myoblast
      differentiation in vitro is enhanced by inhibiting a proliferation-promoting
      miRNA (miR-133) expressed in muscle tissues. As assessed by functional force
      measurements in response to electrical stimulation at frequencies ranging from 0
      to 20 Hz, peak forces exhibited by BAMs with miR-133 inhibition (anti-miR-133)
      were on average 20% higher than the corresponding negative control, although
      dynamic responses to electrical stimulation in miRNA-transfected BAMs and
      negative controls were similar to nontransfected controls. Immunostaining for
      alpha-actinin and myosin also showed more distinct striations and myofiber
      organization in anti-miR-133 BAMs, and fiber diameters were significantly larger
      in these BAMs over both the nontransfected and negative controls. Compared to the
      negative control, anti-miR-133 BAMs exhibited more intense nuclear staining for
      Mef2, a key myogenic differentiation marker. To our knowledge, this study is the
      first to demonstrate that miRNA mediation has functional effects on tissue
      engineered constructs.

PMID- 20670164
TI  - Association of genetic polymorphisms with hepatotoxicity in patients with
      childhood acute lymphoblastic leukemia or lymphoma.
AB  - The objective of this study was to identify novel pharmacogenetic determinants of
      treatment-related hepatotoxicity during the maintenance phase in children with
      acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LBL). Although the
      authors first determined whether genotypes of drug-metabolizing enzymes and
      transporters--glutathione S-transferase (GST) genes, GSTM1 positive/null, GSTT1
      positive/null and GSTP1 A313G, methylenetetrahydrofolate reductase (MTHFR) C677T,
      reduced folate carrier 1 (RFC1) G80A, and breast cancer resistant protein (BCRP)
      C421A--were associated with hepatotoxicity for 24 patients, no significant
      difference was detected for genotype and allelic frequencies between the patients
      with and those without severe treatment-related hepatotoxicity. Therefore, the
      authors explored potential candidate polymorphisms associated with hepatotoxicity
      using the Illumina Infinium HumanHap300, encompassing more than 318,000 tag
      single-nucleotide polymorphisms (SNPs), for 8 of 24 patients with or without
      severe hepatotoxicity. Genome-wide genotyping uncovered a total of 28 candidate
      SNPs. rs1966862, in Rho GTPase-activating protein 24 (ARHGAP24), was the most
      significant of the candidates, and the genotypes of rs13424027 (PARD3B),
      rs1156304 (KCNIP4), rs10255262 (SLC13A1), rs7403531 (RASGRP1), and rs381423
      (unidentified gene) were also significantly associated with severe
      hepatotoxicity. This study suggested rs1966862 (ARHGAP24) and the other SNPs to
      be predictive factors for drug-induced hepatotoxicity during the maintenance
      phase in pediatric patients with ALL or LBL.

PMID- 20670165
TI  - Myelofibrosis in children: experience at a single tertiary care center in India.
AB  - The authors describe 10 cases of myelofibrosis diagnosed and managed at their
      center over 16 years. There were 2 and 8 cases, respectively, of primary and
      secondary myelofibrosis. All patients presented with fever, pallor,
      hepatosplenomegaly, and/or lymphadenopathy. Hodgkin's lymphoma (n = 4),
      neuroblastoma (n = 1), thrombasthenic thrombopathy (n = 1), and retroperitoneal
      mass (n = 1) were causal in 7 patients, whereas the diagnosis could not be
      established in a sole case of secondary myelofibrosis. Patients were managed with
      chemotherapy and appropriate care. However, outcome was poor. The authors
      emphasize variable clinical-laboratory spectrum of myelofibrosis, highlight
      management concerns, and demonstrate that prognosis/outcome depends upon
      appropriate management of the underlying condition.

PMID- 20670166
TI  - Thrombin activatable fibrinolysis inhibitor (TAFI): relationship to hemostatic
      alteration in patients with beta-thalassemia.
AB  - Profound hemostatic changes have been observed among thalassemic patients.
      Thrombin activatable fibrinolysis inhibitor (TAFI) is a newly discovered protein
      that potentially attenuates fibrinolysis. The authors aimed to investigate plasma
      level of TAFI in beta-thalassemia patients in relation to clinical severity and
      hemostatic alteration. Fifty-one thalassemic patients (mean age 10.79 +/- 5.59
      years) (21 splenectomized thalassemia major patients, 18 nonsplenectomized
      thalassemia major patients, 12 nonsplenectomized thalassemia intermedia) were
      recruited from Pediatric Hematology Clinic, Ain Shams University; in addition, 32
      healthy age- and sex-matched controls (10.31 +/- 5.58 years) were also included.
      In addition to clinical assessment, laboratory investigations included complete
      blood count (CBC), hemoglobin electrophoresis, prothrombin time (PT), activated
      partial thromboplastin time (PTT), liver function tests, viral hepatitis markers,
      serum ferritin, and plasma TAFI levels. Nine out of 51 patients (17.5%) suffered
      from bleeding manifestations mainly in the form of epistaxis; none of the studied
      patients had thromboembolism. Significant reduction in TAFI levels was shown in
      thalassemic patients compared to controls (P < .0001), in splenectomized compared
      to nonsplenectomized thalassemia group (P < .0001), and in thalassemia major
      compared to thalassemia intermedia group (P < .0001). Negative correlation was
      present between TAFI levels and both liver enzymes and serum ferritin levels (P <
      .05). Thalassemic patients suffering from bleeding showed lower mean TAFI levels
      compared to those not suffering from bleeding (P < .001). Marked reduction in
      TAFI levels was observed in thalassemic patients with splenectomy, altered liver
      functions, and poor chelation who therefore might be at a higher risk for altered
      hemostasis.

PMID- 20670167
TI  - A report of 8 cases with hemoglobin H disease in an Iranian family.
AB  - alpha-Thalassemia is a common genetic disorder in Iran. However, no comprehensive
      data on epidemiology of severe forms of alpha-thalassemia, including hemoglobin H
      (HbH) or hydrops fetalis, is available in this population. This is a first case
      report of an Iranian family with large number of HbH individuals. The proband is
      a 48-year-old woman, referred to our center with anemia and no history of
      previous blood transfusions. Similar clinical phenotype has been observed in all
      of her 5 siblings, 2 of her 4 children, and her granddaughter, whose parents are
      first cousins. A reverse hybridization assay covering 21 alpha globin mutations
      was performed to determine the genotype in 11 members of this family and a fetus.
      HbH genotype was identified in 9 individuals, representing 3 generations,
      including a fetus. The high prevalence of alpha-thalassemia carriers together
      with the high rate of consanguineous marriages could lead to a large number of
      individuals with HbH or even hydrops fetalis in Iranian families. Therefore, to
      avoid the risk of having affected offspring, carrier detection, genetic
      counseling, and prenatal diagnosis would be of vital importance for individuals
      with low red blood cell (RBC) indices, normal iron status, and normal HbA(2)
      level, who are suspected to be alpha-thalassemia carriers.

PMID- 20670169
TI  - Control of transmission of infection in hospitals requires more than clean hands.

PMID- 20670168
TI  - Severe thrombocytopenia with iron deficiency anemia.
AB  - Although severe thrombocytopenia has been reported among children with iron
      deficiency anemia, the presence of both anemia and thrombocytopenia can suggest
      serious or malignant bone marrow dysfunction, requiring further work-up. This
      paper reviews the management and outcomes of patients with the diagnosis of iron
      deficiency anemia presenting with severe thrombocytopenia. The authors present 4
      pediatric patients with iron deficiency anemia and severe thrombocytopenia at
      initial presentation. Charts were reviewed after approval by the institutional
      review boards at both St. Jude Children's Research Hospital and LeBonheur
      Children's Medical Center in Memphis, Tennessee. All 4 patients' hemoglobin
      concentrations and platelet counts normalized within 1 to 3 weeks of initiating
      iron supplementation, suggesting that in such patients iron supplementation can
      obviate the need for invasive diagnostic procedures. In addition, these patients
      all had a platelet "overshoot" phenomenon during iron therapy prior to
      normalization of platelet counts, the mechanism of which is still unknown. The
      literature exploring the mechanism behind the current clinical findings is
      reviewed.

PMID- 20670170
TI  - Modeling animal landscapes.
AB  - There is an increasing need to assess the effects of climate and land-use change
      on habitat quality, ideally from a mechanistic basis. The symposium "Molecules to
      Migration: Pressures of Life" at the Fourth International Conference in Africa
      for Comparative Physiology and Biochemistry, Maasai Mara National Reserve, Kenya,
      2008, illustrated how the principles of biophysical ecology can capture the
      mechanistic links between organisms, climate, and other habitat features. These
      principles provide spatially explicit assessments of habitat quality from a
      physiological perspective (i.e., "animal landscapes") that can be validated
      independently of the data used to derive and parameterize them. The contents of
      this symposium showcased how the modeling of animal landscapes can be used to
      assess key issues in applied and theoretical ecology. The presentations included
      applications to amphibians, reptiles, birds, and mammals. The rare Arabian oryx
      on the Arabian Peninsula is used as an example for energetic calculations and
      their implications for behavior on the landscape.

PMID- 20670171
TI  - Association of profoundly impaired immune competence in H1N1v-infected patients
      with a severe or fatal clinical course.
AB  - BACKGROUND: Pandemic A/H1N1v influenza is characterized by a mild clinical
      course. However, a small subset of patients develops a rapidly progressive course
      caused by primary viral pneumonia or secondary bacterial infections that, in many
      cases, lead to death due to respiratory failure. The aim of the present study was
      to analyze the involvement of the immune response in the clinical presentation of
      H1N1v influenza. METHODS: The differentiation and functional capability of T
      cells from H1N1v-infected patients presenting with either mild disease (n=22) or
      severe or fatal disease (n=6) were compared. Moreover, plasma cytokines and
      chemokines were quantified. RESULTS: T cells from H1N1v-infected patients
      presenting with a severe clinical course resulted in impaired effector cell
      differentiation and failed to respond to mitogenic stimulation. T cell anergy was
      strictly associated with a severe acute phase of infection, but T cells could be
      restored in patients able to recover. Of interest, massive expression of CD95
      marker was found on anergic T cells, suggesting an apoptosis-related mechanism.
      Finally, lower plasma levels of interferon-alpha and monocyte chemoattractant
      protein-1 were found in patients with a worse clinical course of influenza,
      suggesting impaired production of these cytokines. CONCLUSIONS: Our results show
      a strict association between host immune competence and the severity of the
      clinical course of H1N1v infection. By monitoring host functional response,
      patients with an enhanced risk of developing influenza-associated severe
      complications could be identified in a timely manner.

PMID- 20670172
TI  - The role of mucoidy in virulence of bacteria from the Burkholderia cepacia
      complex: a systematic proteomic and transcriptomic analysis.
AB  - Bacteria of the Burkholderia cepacia complex (BCC) are associated with severe
      infection in cystic fibrosis. Recent evidence shows that the mucoid phenotype is
      common in BCC bacteria; however, during chronic infection, transitions from the
      mucoid to nonmucoid morphology have been shown to take place. Here we use RNA
      microarray and proteomic isobaric tagging relative and absolute quantitation
      technologies to gain insight into a pair of mucoid and nonmucoid isolates of B.
      cenocepacia obtained from a chronically infected patient with cystic fibrosis in
      the year prior to her death. During chronic infection, the mucoid isolate lost
      the B. cepacia epidemic strain marker and acquired a mutation in the cepR gene.
      In the nonmucoid isolate, we observed overexpression at both the RNA and protein
      level of several described putative virulence factors, including a nematocidal
      protein AidA and the oxidative stress response protein AhpC. We show that this
      translates into increased resistance to oxidative stress in the nonmucoid
      isolate, a key microbial determinant for resistance against phagocytic cell
      killing. These data illuminate the biological differences between mucoid and
      nonmucoid BCC bacteria, provide targets for elucidating the genetic control of
      exopolysaccharide production in the BCC, and highlight that chronic infection can
      produce both genetically and phenotypically distinct microbial variants in the
      cystic fibrosis lung.

PMID- 20670176
TI  - Using genomics to develop novel antibacterial therapeutics.
AB  - As the genomics era matures, the availability of complete microbial genome
      sequences is facilitating computational approaches to understand bacterial
      genomes and DNA structure/function relationships. From the genome of pathogens,
      we can derive invaluable information on potential targets for new antimicrobial
      agents. Advancements in high-throughput 'omics' technologies and the availability
      of multiple isolates of the same species have significantly changed the time
      frame and scope for identifying novel therapeutic targets. This article aims to
      discuss selected aspects of the bacterial genome, and advocates 'omics'-based
      techniques to advance the discovery of new therapeutic targets against
      extracellular bacterial pathogens.

PMID- 20670177
TI  - Potential of transglutaminase 2 as a therapeutic target.
AB  - IMPORTANCE OF THE FIELD: Increased expression and activity of transglutaminase 2 
      a calcium-dependent enzyme which catalyzes protein cross-linking, polyamination
      or deamidation at selective glutamine residues - are involved in the
      etiopathogenesis of several pathological conditions, such as neurodegenerative
      disorders, autoimmune diseases and inflammatory diseases. Inhibition of enzyme
      activity has potential for therapeutic management of these diseases. AREAS
      COVERED IN THIS REVIEW: The major results achieved in the last twelve years of
      research in the field of inhibition of tranglutaminase activity using cell
      cultures as well as in vivo models of high-social-impact or widespread diseases,
      such as CNS neurodegenerative disorders, celiac sprue, cancer and fibrotic
      diseases. WHAT THE READER WILL GAIN: Beneficial effects of enzyme activity
      inhibition have been observed in neurodegeneration and fibrosis in vivo models by
      delivery of the competitive inhibitor cystamine and more recently designed
      inhibitors, such as thiomidaziolium or norleucine derivatives, which irreversibly
      bind the active site cysteine residue. Transglutaminase 2 targeting with specific
      antibodies has also been shown to be a promising tool for celiac disease
      treatment. TAKE HOME MESSAGE: New insights from transglutaminase inhibition
      studies dealing with side effects of in vivo administration of pan
      transglutaminase inhibitors will help in design of novel therapeutic approaches
      to various diseases.

PMID- 20670178
TI  - Emerging drugs for actinic keratosis.
AB  - IMPORTANCE OF THE FIELD: Actinic keratoses (AK) represent a worldwide problem
      with continuously increasing incidence. AK are characterized by a proliferation
      of atypical keratinocytes limited to the epidermis, but they may develop into
      invasive squamous cell carcinoma. In this regard, novel treatment modalities have
      been developed that allow treatment of the whole actinically damaged field. AREAS
      COVERED IN THIS REVIEW: An overview about current treatment modalities for AK
      including, among others, their mechanism of action, application scheme and common
      side effects. Furthermore, recent developments in the field are described and
      future aspects are discussed. WHAT THE READER WILL GAIN: The reader of this
      review will be informed about all current treatment modalities for AK.
      Furthermore, the reader will gain knowledge about ongoing research in this field
      and novel topical drugs for the treatment of AK. TAKE HOME MESSAGE: Many
      treatment modalities are available for the treatment of AK. Recent developments
      have focused on the management of the whole actinically damaged field. In this
      regard, several topical drugs have been approved for AK, differing in clearance
      rates, side effects, application and cost. Research is continuing aiming in the
      development of the "ideal" treatment of AK which combines high clearance rates
      with few side effects, short treatment duration and low costs.

PMID- 20670179
TI  - Understanding the molecular basis for cardiomyocyte cell cycle regulation: new
      insights in cardiac regeneration after injury?

PMID- 20670180
TI  - The relationship between exercise and the healthy heart: trouble in paradise?

PMID- 20670181
TI  - Dronedarone: NICE enough?

PMID- 20670183
TI  - Pioglitazone: beyond glucose control.
AB  - Pioglitazone is an oral antidiabetic agent that decreases insulin resistance in
      adipose tissue, liver and muscles. This action is mediated by its link to a
      nuclear receptor called peroxisome proliferator-activated receptor-gamma. By
      improving insulin sensitivity, hepatic glucose production decreases and glucose
      uptake increases in the peripheral tissues. Beyond these effects on glucose
      metabolism, pioglitazone has positive effects on lipid metabolism, blood
      pressure, endothelial function, adiponectin and C-reactive protein levels. These
      make pioglitazone treatment effective beyond glucose control. In this article,
      current evidence concerning pioglitazone in the treatment of Type 2 diabetes will
      be reviewed.

PMID- 20670184
TI  - Update on the clinical development of cangrelor.
AB  - Antiplatelet drugs represent the cornerstone of treatment for cardiovascular
      atherothrombotic disease. Dual oral antiplatelet therapy with aspirin and oral
      ADP-receptor antagonists, such as clopidogrel, has been the standard choice for
      prevention of ischemic events in patients with acute coronary syndrome and in
      those undergoing percutaneous coronary intervention. However, due to the
      limitations of clopidogrel, such as interindividual-response variability, drug
      drug interactions, slow onset of action and irreversible inhibitory effects,
      novel antiplatelet agents are under clinical development. Cangrelor is a
      reversible, potent, competitive inhibitor of the ADP P2Y(12) receptor that is
      administered intravenously and rapidly achieves near complete inhibition of ADP
      induced platelet aggregation. These pharmacological properties make cangrelor a
      promising drug for clinical use. However, recent large-scale Phase III clinical
      investigations failed to show significant clinical benefit on the primary end
      point with cangrelor. This article provides an overview of the current status of
      knowledge on cangrelor, focusing on its pharmacologic properties and clinical
      development.

PMID- 20670185
TI  - Pitavastatin for the treatment of primary hyperlipidemia and mixed dyslipidemia.
AB  - Pitavastatin is a new, synthetic member of the statin class of lipid-lowering
      drugs. Compared with other available statins, it has a unique cyclopropyl group
      on its base structure that is believed to increase 3-hydroxy-3-methylglutaryl
      coenzyme A reductase inhibition by a factor of five and to significantly increase
      the transcription and activity of LDL receptors. Pitavastatin is primarily
      metabolized via glucuronidation and is not a substrate for the cytochrome P450
      3A4 enzyme, thus avoiding the potential for cytochrome P450-mediated drug-drug
      interactions. Clinical trials have shown that pitavastatin is comparable to
      atorvastatin and simvastatin in improving lipid measures, and more potent than
      pravastatin. Pitavastatin is effective in reducing triglycerides and increasing
      HDL-cholesterol, so it will be particularly beneficial in treating patients with
      mixed dyslipidemia. Its safety and adverse event profile is similar to that of
      other available statins, and it has an established history of use in Asia
      indicating tolerability and safety for treatment lasting up to 7 years.

PMID- 20670186
TI  - Improving risk stratification for cardiovascular disease.
AB  - Identifying people at high risk of cardiovascular events is the cornerstone of
      cardiovascular disease prevention and a major challenge for healthcare worldwide.
      Recently, both inflammatory and oxidative markers have been shown to improve
      cardiovascular risk prediction models in a wide range of patients. Here, we
      evaluate a recent publication investigating the value of inflammatory and
      oxidative markers for the prediction of cardiovascular mortality in patients with
      stable coronary artery disease. This study shows that the use of multiple markers
      may increase the predictive power of traditional risk models. The findings are
      discussed in the context of cardiovascular risk prediction in general.

PMID- 20670187
TI  - The importance of instability and visit-to-visit variability of blood pressure.
AB  - Spontaneous fluctuations of blood pressure from visit to visit have usually been
      disregarded as a trivial factor that confounds the 'true' associations of an
      individual's long-term average blood pressure with disease. The paper under
      evaluation shows that visit-to-visit blood pressure variability is an independent
      predictor of future cardiovascular events in hypertensive patients and in
      subjects surviving a transient cerebral ischemia. Episodic elevations of blood
      pressure in nonhypertensive subjects seem to carry similar adverse prognostic
      significance. There is some evidence that different blood pressure-lowering drug
      classes may differ in their effects on visit-to-visit blood pressure variability,
      but these findings need to be confirmed in further studies.

PMID- 20670188
TI  - What has happened to multiple arterial grafting in coronary artery bypass
      grafting surgery?
AB  - Coronary artery bypass grafting (CABG) is a well-established therapy for patients
      with multivessel coronary artery disease, with excellent short- and medium-term
      results. This is best illustrated by studies comparing percutaneous coronary
      interventions (PCIs) with CABG surgery, where CABG continues to offer better
      event-free survival. However, there has been increasing concern about the long
      term patency of vein grafts utilized for CABG when compared with arterial grafts.
      Some have suggested that revascularization with arterial grafts rather than vein
      grafts may result in improved outcomes following CABG. This is particularly
      important when one considers that graft occlusion can result in recurrence of
      disabling angina, rehospitalization, reintervention and death. To date, however,
      multiple arterial grafts have yet to become the standard approach for patients
      undergoing CABG. This is best exemplified by reports from large registries
      suggesting that the use of multiple arterial grafting is limited to approximately
      10% of all patients undergoing CABG. In this article, we will provide some of the
      evidence outlining the risk and benefits of multiple arterial grafting, but more
      importantly, begin to explore why the utilization of multiple arterial grafting
      does not appear to be increasing significantly.

PMID- 20670189
TI  - Cell therapy for heart failure: the need for a new therapeutic strategy.
AB  - Improvements in the treatment of ischemic heart disease have led to a significant
      growth in the numbers of patients with systolic heart failure secondary to
      myocardial injury. Current therapies fail to address the loss of contractile
      tissue due to myocardial injury. Cell therapy is singular in its promise of
      primarily treating this underlying issue through salvage of viable myocardium or
      generation of new contractile tissue. Multiple cell types have been used to
      target acute myocardial infarction, chronic ischemic heart disease and heart
      failure due to infarction. Bone marrow mononuclear cells have been used to
      increase myocardial salvage after acute infarction. Randomized trials of over 800
      patients have demonstrated no safety issues, and meta-analyses have suggested an
      improvement in left ventricular function in treated patients with trends toward
      improvements in hard cardiac end points. Cell therapy for chronic ischemic heart
      disease with bone marrow angiogenic progenitors has shown similar safety and
      trends toward improvement in function. While these therapies have targeted
      patients with viable myocardium, myoblasts have been used to treat patients with
      left ventricular dysfunction secondary to transmural infarction. Cell types with
      cardiomyogenic potential, including induced pluripotent stem cells and cardiac
      progenitor cells, offer the promise of true myocardial regeneration. Future
      studies with these cells may open the door for true myocardial regeneration.

PMID- 20670190
TI  - Gene therapy and angiogenesis in patients with coronary artery disease.
AB  - Not all patients with severe coronary artery disease can be treated
      satisfactorily with current recommended medications and revascularization
      techniques. Various vascular growth factors have the potential to induce
      angiogenesis in ischemic tissue. Clinical trials have only evaluated the effect
      of VEGF and FGF in patients with coronary artery disease. The initial small and
      unblinded studies with either recombinant growth factor proteins or genes
      encoding growth factors were encouraging, demonstrating both clinical improvement
      and evidence of angiogenesis. However, subsequent larger double-blind placebo
      controlled trials could not confirm the initial high efficacy of either the
      growth factor protein or the gene therapy approaches observed in earlier small
      trials. The clinical studies so far have all been without any gene-related
      serious adverse events. Future trials will focus on whether an improvement in
      clinical results can be obtained with a cocktail of growth factors or by a
      combination of gene and stem cell therapy in patients with severe coronary artery
      disease, which cannot be treated effectively with current treatment strategies.

PMID- 20670191
TI  - Bone marrow-derived cells and hypertension.
AB  - Although it is clear that inadequate perfusion underlies most of the organ
      dysfunction accounting for hypertension-related adverse outcomes, our
      understanding of the pathophysiologic mechanisms is still evolving. The most
      important approaches to improving vascular health include reducing injury to the
      vessel wall and enhancing mechanisms to repair/restore vessel wall function. The
      main factors responsible for repairing cardiovascular function include vascular
      progenitor cells and angiogenesis. The purpose of this article is to bring
      together recent findings indicating that limitations in vascular progenitor cell
      function seen in hypertension underlie the increased risks for coronary artery
      disease and other vascular-related adverse outcomes. Improved understanding of
      systems for vascular repair holds promise for new therapeutic applications in the
      future, although this subject will not be dealt with in this article. We will
      focus on a pivotal defense mechanism - bone marrow-derived progenitor cells and
      their roles in hypertension.

PMID- 20670192
TI  - Stem cell labeling for noninvasive delivery and tracking in cardiovascular
      regenerative therapy.
AB  - Clinical and basic scientific studies of stem cell-based therapies have shown
      promising results for cardiovascular diseases. Despite a rapid transition from
      animal studies to clinical trials, the mechanisms by which stem cells improve
      heart function are yet to be fully elucidated. To optimize cell therapies in
      patients will require a noninvasive means to evaluate cell survival,
      biodistribution and fate in the same subject over time. Cell labeling offers the
      ability to image distinct cell lineages in vivo and investigate the efficacy of
      these therapies using standard noninvasive imaging techniques. In this article,
      we will discuss the most promising cell labeling techniques for translation to
      clinical cardiovascular applications.

PMID- 20670194
TI  - Cardiac magnetic resonance imaging: current status and future directions.
AB  - Cardiac MRI (CMR) provides a comprehensive evaluation of cardiac function and
      anatomy, as well as myocardial tissue characterization and perfusion. New data
      show the potential for CMR to analyze left ventricular diastolic function,
      coronary plaque and myocardial oxygen levels. A growing body of animal and
      clinical data on molecular imaging, hybrid imaging and interventional CMR holds
      promise for more widespread clinical application. Technological advances in body
      coils, 3-T systems, imaging sequences and novel applications such as T1 mapping
      will expand the application and quality of CMR.

PMID- 20670195
TI  - Mechanism of action and clinical development of platelet thrombin receptor
      antagonists.
AB  - Atherothrombotic disease is the leading cause of death worldwide. Currently, dual
      antiplatelet therapy with aspirin and ADP receptor antagonists has shown improved
      short- and long-term clinical outcomes but is associated with increased bleeding
      risk, and the rates of recurrent ischemic events still remain high. Selective
      inhibition of the principal protease-activated receptor (PAR)-1 for thrombin, the
      most potent platelet activator, represents a promising novel strategy to reduce
      ischemic events without increasing the risk of bleeding. Two PAR-1 antagonists
      are currently being tested in clinical trials: SCH 530348 and E5555. Both have
      demonstrated an antiplatelet effect without increasing bleeding time in
      preclinical trials. Results of Phase II trials showed that SCH 530348, in
      addition to standard antiplatelet therapy, was well tolerated and not associated
      with increased bleeding risk. The safety and tolerability of E5555 is being
      evaluated in patients with coronary artery disease and non-ST-segment elevation
      acute coronary syndrome in four Phase II clinical trials. Two large-scale Phase
      III trials assessing the efficacy of SCH 530348 in addition to the standard of
      care are currently ongoing. This article provides an overview of the current
      status of knowledge on platelet thrombin receptor antagonists, focusing on
      pharmacologic properties and clinical development.

PMID- 20670197
TI  - Pramipexole extended-release (once-daily formulation) for the treatment of
      Parkinson's disease.
AB  - IMPORTANCE OF THE FIELD: Immediate-release pramipexole (P-IR) is indicated three
      times daily for the symptomatic treatment of early and advanced Parkinson's
      disease (PD). An extended-release formulation of pramipexole (P-ER) has been
      developed to allow a once-daily formulation and to provide more stable
      dopaminergic stimulation. AREAS COVERED IN THIS REVIEW: This review summarizes
      clinical pharmacology and pharmacokinetics of P-ER for the treatment of early and
      advanced PD. The advantages and disadvantages of the strategies available at
      present for achieving continuous dopaminergic stimulation in the treatment of PD
      are discussed first. The pharmacological properties are then summarized. Finally,
      the clinical pharmacology and pharmacokinetics of P-ER are described. WHAT THE
      READER WILL GAIN: The reader will gain knowledge of the development of P-ER, its
      current place in the pharmacotherapy of PD, and future directions. TAKE HOME
      MESSAGE: P-ER has been shown to be efficacious in early and advanced PD and it
      has the same clinical profile when administered once daily as P-IR administered
      three times daily. An overnight switching of P-IR to dose-equivalent P-ER is
      successful in 80% of patients with early PD.

PMID- 20670193
TI  - Emerging concepts in the pharmacogenomics of arrhythmias: ion channel
      trafficking.
AB  - Continuous, rhythmic beating of the heart requires exquisite control of
      expression, localization and function of cardiac ion channels - the foundations
      of the cardiac myocyte action potential. Disruption of any of these processes can
      alter the shape of the action potential, predisposing to cardiac arrhythmias.
      These arrhythmias can manifest in a variety of ways depending on both the
      channels involved and the type of disruption (i.e., gain or loss of function). As
      much as 1% of the population of developed countries is affected by cardiac
      arrhythmia each year, and a detailed understanding of the mechanism of each
      arrhythmia is crucial to developing and prescribing the proper therapies. Many of
      the antiarrhythmic drugs currently on the market were developed before the
      underlying cause of the arrhythmia was known, and as a result lack specificity,
      causing side effects. The majority of the available drugs target the conductance
      of cardiac ion channels, either by blocking or enhancing current through the
      channel. In recent years, however, it has become apparent that specific targeting
      of ion channel conductance may not be the most effective means for treatment.
      Here we review increasing evidence that suggests defects in ion channel
      trafficking play an important role in the etiology of arrhythmias, and small
      molecule approaches to correct trafficking defects will likely play an important
      role in the future of arrhythmia treatment.

PMID- 20670198
TI  - Topical vaginal estrogen therapy in managing postmenopausal urinary symptoms: a
      reality or a gimmick?
AB  - Postmenopausal estrogen deprivation has been suggested as a risk factor for lower
      urinary tract dysfunction including stress incontinence, overactive bladder and
      recurrent urinary tract infection. These symptoms could have enormous effects on
      individuals and health-care providers in terms of impact on quality of life and
      cost. Recent randomized, controlled trials suggested that systemic hormone
      replacement therapy does have a negative effect on female lower urinary tract
      function, probably because of the progestogen component. Further, it may be
      unacceptable for many women because of concerns about breast cancer or the return
      of withdrawal bleeding. Topical vaginal estrogen preparations reverse urogenital
      atrophic changes and may relieve associated urinary symptoms while avoiding
      systemic and progestogenic effects. This article provides an up-to-date overview
      of the role, effectiveness and safety of topical vaginal estrogen therapy for the
      treatment of lower urinary tract symptoms in postmenopausal women.

PMID- 20670199
TI  - Transdermal hormone therapy and the risk of stroke and venous thrombosis.
AB  - Recent case-control and cohort studies have indicated that the transdermal
      administration of postmenopausal estrogen therapy is not associated with an
      increased risk of cardiovascular complications, specifically stroke and venous
      thrombosis. These studies have prompted the clinical promotion of transdermal
      treatment as 'safer'. There are reasons, however, to be cautious regarding
      postmenopausal transdermal hormone therapy, especially in regard to stroke.
      Previous reports linking postmenopausal estrogen therapy and the risk of stroke
      have not yielded consistent results, finding it difficult to adjust for all
      confounding factors, including compliance with treatment. Age of the population
      studies may be a critical issue. Notably, the risk of stroke with oral estrogen
      was not increased in the Women's Health Initiative when women with prior
      cardiovascular disease or those older than 60 years were excluded. There does
      appear to be a dose-response relationship with stroke, similar to that observed
      with estrogen-progestin contraceptives, and this may be a problem when studying
      standard doses of transdermal treatment, in that many women receiving transdermal
      estrogen display lower estrogen blood levels when compared with oral treatment.
      Clinicians should administer low doses of estrogen to women with risk factors for
      stroke, and the transdermal route of administration is indicated for women at
      high risk for venous thrombosis and for older postmenopausal women, especially
      for women with stroke risk factors. In a recent study, Renoux and colleagues from
      McGill University in Montreal performed a nested case-control study deriving the
      data from a cohort of women in the UK General Practice Research Database (GPRD).
      Current use of oral and transdermal hormone therapy, based on recorded
      prescriptions, was compared to no use in 15 710 cases and 59 958 controls. The
      adjusted rate ratio (RR) for stroke for current use of transdermal estrogens,
      with or without a progestin, was not increased (RR 0.95; 95% confidence interval
      (CI) 0.75-1.20) compared with a significant increase associated with oral
      estrogen, with or without a progestin (RR 1.28; 95% CI 1.15-1.42). This would
      amount to an attributal risk of 0.8 additional strokes per 1000 women per year.
      There was an indication of a dose-response relationship; a significant increase
      in risk was observed with transdermal estrogen doses greater than 50 microg. The
      case-control study by Renoux and colleagues is the first major analysis to
      compare transdermal and oral hormone therapy and conclude that, compared with an
      increased risk of stroke with oral therapy, there was no increased risk with
      transdermal treatment at a dose of 50 microg or less. This report is about as
      strong an observational study as can be achieved. Large numbers of cases (15 710)
      and controls (59 958) were available for analysis using the well-known UK GPRD.
      The use of this computerized database precludes selection bias by the
      investigators and recall bias by the women in the study. The results support the
      growing conventional wisdom that transdermal therapy at standard doses is free of
      the cardiovascular risks associated with oral therapy.

PMID- 20670200
TI  - Male menopause: is it a real clinical syndrome?
AB  - The association between aging-related testosterone deficiency and late-onset
      clinical hypogonadism in men remains a controversial concept. Several descriptive
      names, such as andropause, male menopause, partial androgen deficiency of the
      aging male and late-onset hypogonadism, have been suggested in an attempt to
      connect the age-related decline in androgen production and symptoms of aging in
      men. However, despite many studies, no clear correlation has been established
      and, as a result, there is also a debate over the use of androgen replacement
      therapy in this clinical set-up. Nevertheless, new data from large-scale studies
      have been recently published, which shed more light on this complicated issue. A
      recent New England Journal of Medicine article demonstrated that only a minor
      fraction (2%) of elderly men suffer from this clinical syndrome and gave serum
      testosterone level thresholds that support it.

PMID- 20670202
TI  - TRPM2 channel properties, functions and therapeutic potentials.
AB  - IMPORTANCE OF THE FIELD: Oxidative stress, through production of reactive oxygen
      species, triggers disturbance in intracellular calcium [Ca(2+)](i) homeostasis,
      which has been identified as an important causative factor in the pathogenesis of
      numerous inflammatory, cardiovascular and neurodegenerative diseases. AREAS
      COVERED IN THIS REVIEW: Transient receptor potential melastatin 2 (TRPM2) protein
      forms a Ca(2+)-permeable cationic channel that is activated in response to
      oxidative stress and therefore acts as a cellular redox sensor. Research over the
      years has substantially advanced the knowledge of expression and functional
      properties of the TRPM2 channel, and particularly has accumulated compelling
      evidence for an important role for TRPM2 channel-mediated extracellular Ca(2+)
      influx in several physiological and pathophysiological functions exemplified by
      insulin release from pancreatic beta-cells, production of pro-inflammatory
      cytokines from immune cells, increased endothelial permeability, microglia
      activation and cell death. These findings suggest therapeutic potential of the
      TRPM2 channel as a drug target for combating oxidative-stress-related diseases.
      WHAT THE READER WILL GAIN: The current state of knowledge with respect to the
      TRPM2 channel properties and the roles in oxidant stress signalling and
      functions. TAKE HOME MESSAGE: TRPM2 may be a novel therapeutic target for
      oxidative stress-related diseases.

PMID- 20670203
TI  - Developmental implications of nonlinear phonological theory.
AB  - For the past 20 years the field of linguistics has provided a basis for
      assessment and treatment methods for speech and language disorders. Since
      Goldsmiths (1976) dissertation showing tone as an independently functioning
      autosegment, new and robust phonological frameworks have become available, i.e.
      nonlinear phonological frameworks. This paper outlines major aspects of nonlinear
      phonology and its developmental implications. Based in generative phonology,
      nonlinear frameworks adhere to many of the tenets of the generative grammar
      tradition, such as markedness and autonomy of linguistic components. The major
      difference between classical and nonlinear generative phonology is the latters
      emphasis on representation rather than on rules or processes. This enriched
      representation is hierarchical and multitiered, rather than being strictly
      sequential as in classical generative phonology, and includes syllabic structure
      and segmental information. Phonological rules or processes result from, and are
      constrained by, principles of association between the various autonomous levels.
      If a child comes to the language-learning situation with a representional
      framework, a set of universal 'templates' are then available to utilize for
      decoding and encoding. The incorporation of both syllabic (prosodic level) and
      segmental information in representation suggests that the child will come to the
      language-learning process primed with expected syllable structure bases as well
      as with an expected segmental 'feature inventory'. The concept of autonomy
      implies possible independent learning for information on the various tiers, e.g.
      between the prosodic and segmental levels. The concept of hierarchy suggests that
      prominent system units in tree structure may have developmental precedence over
      deeply embedded units. These and other concepts are developed in the following
      pages.

PMID- 20670204
TI  - The application of nonlinear phonological theory to intervention with one
      phonologically disordered child.
AB  - Speech-language pathologists gain opportunities to search for more effective
      assessment and intervention methodologies by deriving implications of significant
      developments within linguistics. This paper describes the application of some
      tenets of nonlinear phonology to the planning and execution of a phonological
      intervention programme with one child. The nonlinear analyses provided
      independent phonological therapy goals for both segmental and syllable structure
      (prosodic tier structure) development. Higher and lower level features in the
      feature hierarchy were contrasted in intervention. Prosodic constituents derived
      from moraic and onset-rime syllable theories were contrasted as facilitators in
      the attainment of syllable structure goals. A detailed analysis of the changes in
      the childs speech over two 6-week intervention blocks shows that the goals
      derived from the nonlinear analyses were logical and attainable. The data
      demonstrate a faster rate of acquisition for syllable structure (prosodic) goals
      in the first time block, some predictability for acquisition based on the feature
      hierarchy, and similarity of effectiveness of the use of different types of
      prosodic constituent stimuli.

PMID- 20670205
TI  - The ethologic model of phonetic development: 111. The phonetic product.
AB  - The ethologic model of phonetic development supposes that the increased use of
      different places of consonant-like (closant) and vowel-like (vocant) articulation
      defines the growth of phonetic diversity early in life (Bauer, 1988b). To test
      this model, vocalizations were sampled from children during caregiver-child play
      interactions. It was hypothesized that regular development of phonetic diversity
      could be defined by applying a measure, the phonetic product (PP) estimator, to
      the vocalizations of two groups of infants (referred to as the Omaha and Syracuse
      groups). The Omaha group of five children were sampled at 13 and 24 months of
      age, while the Syracuse group of six children were sampled monthly between 8 and
      25 months of age. Phonetic diversity was estimated for each vocalization using
      the weighted PP of counted phones in eight different phonetic categories. The PP
      increased between the two sampling ages for the Omaha group and had a monthly
      growth for the Syracuse group. These findings, relating the PP to age, support
      the hypothesis that phonetic diversity increases as predicted by the ethologic
      model of phonetic development.

PMID- 20670206
TI  - Safety evaluation of tirofiban.
AB  - IMPORTANCE OF THE FIELD: Heightened platelet activity is pivotal in the
      thrombosis underlying acute coronary syndrome (ACS). The glycoprotein IIb/IIIa
      inhibitor tirofiban is a powerful platelet inhibitor with demonstrated efficacy
      and safety across the spectrum of ACS. Despite tirofiban's impact on the platelet
      compared with placebo, only an excess in minor and importantly not major bleeding
      has been observed. Thrombocytopenia with tirofiban seems to be extremely rare and
      immediately reversible on infusion discontinuation. AREAS COVERED IN THIS REVIEW:
      The review includes the rationale for potent antiplatelet therapy in the
      management of ACS, particularly patients at high risk for ischemic complications.
      Additionally, it provides an overview of tirofiban's pharmacology and summary of
      the clinical efficacy and safety data of two dosing regimens. WHAT THE READER
      WILL GAIN: The reader will gain a perspective on the efficacy and safety data
      from the key trials of tirofiban. TAKE HOME MESSAGE: Tirofiban is safe and
      effective in patients with ACS. The single bolus dose regimen produces potent
      platelet inhibition resulting in significant improvement in clinical events over
      placebo when initiated just prior to percutaneous coronary intervention and at
      first medical contact. When compared with abciximab, tirofiban demonstrates
      similar efficacy though significantly lower rates of thrombocytopenia.

PMID- 20670207
TI  - Measurement of fractional exhaled nitric oxide by a new portable device:
      comparison with the standard technique.
AB  - BACKGROUND: Fractional exhaled nitric oxide (FeNO) measurement is a reliable,
      noninvasive marker of airway inflammation. The use of portable FeNO analyzers may
      enable the assessment of airway inflammation in primary care. OBJECTIVE: The
      authors compared FeNO values obtained by a new portable device (NObreath,
      Bedfont, UK) to those of the standard stationary analyzer (NIOX, Aerocrine,
      Sweden) in a large cohort of asthmatic patients. METHODS: One hundred and fifty
      four (age range: 14-83 years, forced expiratory volume in one second [FEV(1)]
      range: 48-134% predicted, asthma control test [ACT] range: 7-25) out of 168
      recruited patients completed the study. Each patient performed at least two valid
      FeNO measurements at a constant flow rate of 50 ml/s on each of the two
      analyzers. RESULTS: A significant relationship between the FeNO values obtained
      by the two devices (r = .95, p < .001) was found. Altman-Bland plot confirmed
      this agreement. Within-patient repeatability was excellent in both devices.
      Intraclass correlation coefficients for NIOX and NObreath values were .925 and
      .967, respectively. By means of receiver operating characteristic curve analysis,
      the FeNO cutoff points that better identified patients with ACT >= 20 were 15 ppb
      (0.84 sensitivity and 0.42 specificity) by NIOX and 25 ppb (0.53 sensitivity and
      0.69 specificity) by NObreath. Easiness to use of both devices, assessed by
      visual analogue scale was not different. CONCLUSION: FeNO measurements obtained
      by the new portable FeNO analyzer are reliable because they are directly
      comparable with those obtained by the stationary standard device. The use of
      portable instruments may facilitate the FeNO measurement in primary care.

PMID- 20670208
TI  - New aminoglycoside antibiotics.
AB  - IMPORTANCE OF THE FIELD: Nosocomial infections caused by multi-drug resistant
      (MDR) Gram-negative bacteria are on the increase, often with few or no
      therapeutic options for treatment. Historically, a successful approach to
      generate novel antibiotics has been the chemical modification of existing
      classes, addressing deficiencies such as resistance mechanisms, safety profile or
      pharmacokinetic parameters. Aminoglycosides (AGs) represent one of the five
      clinically-used classes (AGs, beta-lactams, quinolones, tetracyclines and
      sulfonamides) with activity against Gram-negative bacteria. AREAS COVERED IN THIS
      REVIEW: A summary of the AG patent literature between the beginning of 2005 and
      February 2010 with the main focus on novel AG analogs with potential for
      therapeutic activity against MDR Gram-negative pathogens. WHAT THE READER WILL
      GAIN: Overview of the patent literature in the aminoglycoside field during the
      past 5 years including an assessment of the therapeutic potential for the
      derivatives described. TAKE HOME MESSAGE: A few companies and academic groups
      have recently reawakened the dormant field of AG antibiotics, successfully
      applying novel technologies. So far, this has yielded one clinical candidate,
      ACHN-490, currently undergoing a Phase II evaluation in complicated urinary tract
      infections.

PMID- 20670210
TI  - P-glycoprotein and breast cancer resistance protein affect disposition of
      tandutinib, a tyrosine kinase inhibitor.
AB  - Tandutinib is a tyrosine kinase inhibitor under investigation for the treatment
      of solid and hematological tumors. We evaluated efflux transporter substrate
      specificity of tandutinib in Caco-2 cells, and the role of efflux transporters in
      the disposition of tandutinib in rats and efflux transporter knock-out mice.
      These studies demonstrated that tandutinib is a substrate of P-glycoprotein (P
      gp) and breast cancer resistance protein (BCRP) in Caco-2 cells. In rats,
      administration of GF120918, before treatment with tandutinib orally resulted in
      approximately a seven-fold increase in the mean plasma area under the
      concentration-versus-time curve (AUC) compared to the vehicle control group. In
      mice, after intravenous administration of tandutinib, the mean plasma AUC values
      in the Bcrp1(-/-) mice and Mdr1a/b(-/-) mice was 1.53- and 1.20-fold greater than
      that of the wild type (WT) mice, respectively. After oral administration, the
      drug exposure in Mdr1a/b(-/-), Bcrp1(-/-), and Mdr1a/b(-/-)/Bcrp1(-/-) mice was
      higher than in the WT mice. The brain to plasma exposure ratio (B/P) of
      tandutinib in Mdr1a/b(-/-) mice increased by 2- to 3-fold over that in the WT
      mice. There was a 13-fold increase in B/P in Mdr1a/b(-/-)/Bcrp1(-/-) mice. This
      finding illustrates that P-gp and Bcrp play a role in oral absorption, systemic
      clearance, and brain penetration of tandutinib in the rodents. P-gp affected oral
      absorption and brain penetration of tandutinib to a greater extent than Bcrp, but
      Bcrp contribution to systemic clearance of tandutinib was greater than P-gp.
      Thus, co-administration of efflux pump inhibitors may be a useful strategy to
      enhance tandutinib absorption and brain penetration clinically.

PMID- 20670211
TI  - Daunorubicin metabolism in leukemic cells isolated from patients with acute
      myeloid leukemia.
AB  - BACKGROUND: Anthracyclines like daunorubicin (DNR) are important drugs in the
      treatment of acute myeloid leukaemia (AML). In vitro studies have shown that
      cellular metabolism of anthracyclines could play a role in drug resistance.
      Currently, it is not known what enzyme is responsible for anthracycline
      metabolism in leukemic cells. AIMS: To study C-13 reduction of DNR to
      daunorubicinol (DOL) in leukemic cells isolated from patients with AML and to
      determine the most important enzyme involved. METHODS: Mononuclear blood cells
      from 25 AML patients were isolated at diagnosis and used in a metabolic assay to
      determine the % DOL formed. mRNA and western blot analysis were performed on the
      2 most likely candidates for anthracycline metabolism; carbonyl reductase 1 (CR1)
      and aldoketoreductase 1A1 (AKR1A1). DNR and DOL concentrations were determined by
      HPLC. RESULTS: We found a large interindividual variation (up to 47-fold) in
      leukemic cell DNR metabolism. The specific CR1 inhibitor zeraleone analogue 5
      significantly inhibited DNR metabolism with a mean inhibitory effect of 68 %. No
      correlation between mRNA levels of the enzymes and metabolism were found.
      Cellular DNR metabolism correlated significantly with CR1 protein expression,
      determined by western blot, (p < 0.05, R2 = 0,229) while no significant
      correlation was found with AKR1A1 protein expression. CONCLUSIONS: DNR metabolism
      in AML cells shows a pronounced interindividual variability. Our results support
      that CR1 is the most important enzyme for conversion of DNR to DOL in AML cells.
      This information could in the future be used to genotype CR1 and possibly help to
      individualise dosing.

PMID- 20670212
TI  - Recent developments in the fabrication of ordered nanostructure arrays based on
      nanosphere lithography.
AB  - Since it was invented two decades ago, Nanosphere Lithography (NSL) has been
      widely studied as a low cost and flexible technique to fabricate nanostructures.
      Based on the registered patents and some selected papers, this review will
      discuss recent developments of different NSL strategies for the fabrication of
      ordered nanostructure arrays. The mechanism of self-assembly process and the
      techniques for preparing the self-assembled nanosphere template are first briefly
      introduced. The nanosphere templates are used either as shadow masks or as moulds
      for pattern transfer. Much more work now combines NSL with other lithographic
      techniques and material growth methods to form novel nanostructures of complex
      shape or various materials. Hence, this review finally gives a discussion on some
      future directions in NSL study.

PMID- 20670213
TI  - Prediction of subcellular location of apoptosis proteins using pseudo amino acid
      composition: an approach from auto covariance transformation.
AB  - Knowledge of apoptosis proteins plays an important role in understanding the
      mechanism of programmed cell death. Thus, annotating the function of apoptosis
      proteins is of significant value. Since the function of apoptosis proteins
      correlates with their subcellular location, the information about their
      subcellular location can be very useful in understanding their role in the
      process of programmed cell death. In the present study, we propose a novel
      sequence representation that incorporates the evolution information represented
      in the position-specific score matrices by the auto covariance transformation.
      Then the support vector machine classifier is adopted to predict subcellular
      location of apoptosis proteins. To verify the performance of this method,
      jackknife cross-validation tests are performed on three widely used benchmark
      datasets and results show that our approach achieves relatively high prediction
      accuracies over some classical methods.

PMID- 20670214
TI  - Identification and biophysical assessment of the molecular recognition mechanisms
      between the human haemopoietic cell kinase Src homology domain 3 and ALG-2
      interacting protein X.
AB  - SFKs (Src family kinases) are central regulators of many signalling pathways.
      Their functions are tightly regulated through SH (Src homology) domain-mediated
      protein-protein interactions. A yeast two-hybrid screen using SH3 domains as bait
      identified Alix [ALG-2 (apoptosis-linked gene 2)-interacting protein X] as a
      novel Hck (haemopoietic cell kinase) SH3 domain interactor. The Alix-Hck-SH3
      interaction was confirmed in vitro by a GST (glutathione transferase) pull-down
      assay and in intact cells by a mammalian two-hybrid assay. Furthermore, the
      interaction was demonstrated to be biologically relevant in cells. Through
      biophysical experiments, we then identified the PRR (proline-rich region) motif
      of Alix that binds Hck-SH3 and determined a dissociation constant of 34.5 MUM.
      Heteronuclear NMR spectroscopy experiments were used to map the Hck-SH3 residues
      that interact with an ALIX construct containing the V and PRR domains or with the
      minimum identified interacting motif. Finally, SAXS (small-angle X-ray
      scattering) analysis showed that the N-terminal PRR of Alix is unfolded, at least
      before Hck-SH3 recognition. These results indicate that residues outside the
      canonical PxxP motif of Alix enhance its affinity and selectivity towards Hck
      SH3. The structural framework of the Hck-Alix interaction will help to clarify
      how Hck and Alix assist during virus budding and cell-surface receptor
      regulation.

PMID- 20670215
TI  - Musashi 1-positive cells derived from mouse embryonic stem cells can
      differentiate into neural and intestinal epithelial-like cells in vivo.
AB  - Msi1 (Musashi 1) is regarded as a marker for neural and intestinal epithelial
      stem cells. However, it is still unclear whether Msi1-positive cells derived from
      mouse embryonic stem cells have the ability to differentiate into neural or
      intestinal epithelial cells. A pMsi1-GFP (green fluorescent protein) reporter
      plasmid was constructed in order to sort Msi1-positive cells out of the
      differentiated cell population. The GFP-positive cells (i.e. Msi1-positive cells)
      were sorted by FACS and were hypodermically engrafted into the backs of NOD/SCID
      (non-obese diabetic/severe combined immunodeficient) mice. The presence of neural
      and intestinal epithelial cells in the grafts was detected. Msi1 was highly
      expressed in the GFP-positive cells, but not in the GFP-negative cells. The
      markers for neural cells (Nestin and Tubulin beta III) and intestinal epithelial
      cells [FABP2 (fatty acid binding protein 2), Lyz (lysozyme) and ChA (chromogranin
      A)] were more highly expressed in the grafts from Msi1-positive cells than those
      from Msi1-negative cells (P<0.05). The grafts from the Msi1-negative cells
      contained more mesodermal-like tissues than those from the Msi1-positive cells.
      The pMsi1-GFP vector can be used to sort Msi1-positive cells from a cell
      population derived from mouse embryonic stem cells. The Msi1-positive cells can
      differentiate into neural and intestinal epithelial-like cells in vivo.

PMID- 20670216
TI  - Cadmium regulates copper homoeostasis by inhibiting the activity of Mac1, a
      transcriptional activator of the copper regulon, in Saccharomyces cerevisiae.
AB  - Cadmium is a toxic metal and the mechanism of its toxicity has been studied in
      various model systems from bacteria to mammals. We employed Saccharomyces
      cerevisiae as a model system to study cadmium toxicity at the molecular level
      because it has been used to identify the molecular mechanisms of toxicity found
      in higher organisms. cDNA microarray and Northern blot analyses revealed that
      cadmium salts inhibited the expression of genes related to copper metabolism.
      Western blotting, Northern blotting and chromatin immunoprecipitation experiments
      indicated that CTR1 expression was inhibited at the transcriptional level through
      direct inhibition of the Mac1 transcriptional activator. The decreased expression
      of CTR1 results in cellular copper deficiency and inhibition of Fet3 activity,
      which eventually impairs iron uptake. In this way, cadmium exhibits a negative
      effect on both iron and copper homoeostasis.

PMID- 20670217
TI  - Characterization of the role of dendritic cells in prion transfer to primary
      neurons.
AB  - TSEs (transmissible spongiform encephalopathies) are neurodegenerative diseases
      caused by pathogenic isoforms (PrPSc) of the host-encoded PrPc (cellular prion
      protein). After consumption of contaminated food, PrPSc deposits rapidly
      accumulate in lymphoid tissues before invasion of the CNS (central nervous
      system). However, the mechanisms of prion spreading from the periphery to the
      nervous system are still unclear. In the present study, we investigated the role
      of DCs (dendritic cells) in the spreading of prion infection to neuronal cells.
      First, we determined that BMDCs (bone-marrow-derived DCs) rapidly uptake PrPSc
      after exposure to infected brain homogenate. Next, we observed a progressive
      catabolism of the internalized prion aggregates. Similar experiments performed
      with BMDCs isolated from KO (knockout) mice or mice overexpressing PrP (tga20)
      indicate that both PrPSc uptake and catabolism are independent of PrPc expression
      in these cells. Finally, using co-cultures of prion-loaded BMDCs and cerebellar
      neurons, we characterized the transfer of the prion protein and the resulting
      infection of the neuronal cultures. Interestingly, the transfer of PrPSc was
      triggered by direct cell-cell contact. As a consequence, BMDCs retained the prion
      protein when cultured alone, and no transfer to the recipient neurons was
      observed when a filter separated the two cultures or when neurons were exposed to
      the BMDC-conditioned medium. Additionally, fixed BMDCs also failed to transfer
      prion infectivity to neurons, suggesting an active transport of prion aggregates,
      in accordance with a role of TNTs (tunnelling nanotubes) observed in the co
      cultures.

PMID- 20670218
TI  - Increased oesophageal acid exposure at the beginning of the recumbent period is
      primarily a recumbent-awake phenomenon.
AB  - BACKGROUND: A significant increase in oesophageal acid exposure during early
      recumbent period has been demonstrated. AIM: To determine if acid reflux during
      the early recumbent period occurs in the recumbent-asleep or recumbent-awake
      period using a novel integrative actigraphy and pH programme. METHOD: Thirty-nine
      subjects with heartburn at least three times a week were included. Subjects
      underwent pH testing concomitantly with actigraphy. Simultaneously recorded
      actigraphy and pH data were incorporated using a novel integrative technique to
      determine sleep and awake periods. Characteristics of acid reflux were compared
      between the recumbent-awake and recumbent-asleep periods. RESULTS: Seventeen
      (44.7%) subjects had acid reflux events during recumbent-awake period as compared
      to seven (18.4%) in the corresponding recumbent-asleep period (P = 0.046). The
      mean number of acid reflux events in recumbent-awake period was significantly
      higher than in the corresponding recumbent-asleep period (8.1 +/- 4.4 vs. 3.2 +/-
      1.5, P < 0.001). In the recumbent-awake period, 38.4% of acid reflux events were
      associated with GERD-related symptoms as compared with 3.7% of acid reflux events
      during the corresponding recumbent-asleep period (P = 0.01). CONCLUSION:
      Increased acid reflux in the early recumbent period occurs primarily during the
      recumbent-awake and not during the recumbent-asleep period.

PMID- 20670219
TI  - Diarrhoea during enteral nutrition is predicted by the poorly absorbed short
      chain carbohydrate (FODMAP) content of the formula.
AB  - BACKGROUND: Although it is recognized that diarrhoea commonly complicates enteral
      nutrition, the causes remain unknown. AIM: To identify factors associated with
      diarrhoea in patients receiving enteral nutrition with specific attention to
      formula composition. METHODS: Medical histories of in-patients receiving enteral
      nutrition were identified by ICD-10-AM coding and randomly selected from the year
      2003 to 2008. Clinical and demographic data were extracted. Formulas were
      classified according to osmolality, fibre and FODMAP (fermentable oligo-, di- and
      mono-saccharides and polyols) content. RESULTS: Formula FODMAP levels ranged from
      10.6 to 36.5 g/day. Of 160 patients receiving enteral nutrition, 61% had
      diarrhoea. Univariate analysis showed diarrhoea was associated with length of
      stay >21 days (OR 4.2), enteral nutrition duration >11 days (OR 4.0) and
      antibiotic use (OR 2.1). After adjusting for influencing variables through a
      logistic regression model, a greater than five-fold reduction in risk of
      developing diarrhoea was seen in patients initiated on Isosource 1.5 (P = 0.029;
      estimated OR 0.18). The only characteristic unique to this formula was its FODMAP
      content, being 47-71% lower than any other formula. CONCLUSIONS: Length of stay
      and enteral nutrition duration independently predicted diarrhoea development,
      while being initiated on a lower FODMAP formula reduced the likelihood of
      diarrhoea. As retrospective evaluation does not support a cause-effect
      relationship, an interventional study investigating FODMAPs in enteral formula is
      indicated.

PMID- 20670221
TI  - Modelling prior reproductive history to improve prediction of risk for very
      preterm birth.
AB  - In published studies of preterm birth, analyses have usually been centred on
      individual reproductive events and do not account for the joint distributions of
      these events. In particular, spontaneous and induced abortions have often been
      studied separately and have been variously reported as having no increased risk,
      increased risk or different risks for subsequent preterm birth. In order to
      address this inconsistency, we categorised women into mutually exclusive groups
      according to their reproductive history, and explored the range of risks
      associated with different reproductive histories and assessed similarities of
      risks between different pregnancy histories. The data were from a population
      based case-control study, conducted in Victoria, Australia. The study recruited
      women giving birth between April 2002 and April 2004 from 73 maternity hospitals.
      Detailed reproductive histories were collected by interview a few weeks after the
      birth. The cases were 603 women who had had a singleton birth between 20 and less
      than 32 weeks gestation (very preterm births including terminations of pregnancy)
      and the controls were 796 randomly selected women from the population who had had
      a singleton birth of at least 37 completed weeks gestation. All birth outcomes
      were included. Unconditional logistic regression was used to assess the
      association of very preterm birth with type and number of prior abortions, prior
      preterm births and sociodemographic factors. Using the complex combinations of
      prior pregnancy experiences of women (including nulligravidity), we showed that a
      history of prior childbirth (at term) with no preterm births gave the lowest risk
      of very preterm birth. With this group as the reference category, odds ratios of
      more than two were associated with all other prior reproductive histories. There
      was no evidence of difference in risk between types of abortion (i.e. spontaneous
      or induced) although the risk increased if a prior preterm birth had also
      occurred. There was an increasing risk of very preterm birth associated with
      increasing numbers of abortions. This method of data analysis reveals consistent
      and similar risks for very preterm birth following spontaneous or induced
      abortions. The findings point to the need to explore commonalities rather than
      differences in regard to the impact of abortion on subsequent births.

PMID- 20670222
TI  - Modelling sequence of prior pregnancies on subsequent risk of very preterm birth.
AB  - The prevalence and intractability of preterm birth is known as is its association
      with reproductive history, but the relationship with sequence of pregnancies is
      not well studied. The data were from a population-based case-control study,
      conducted in Victoria, Australia. The study recruited women giving birth between
      April 2002 and April 2004 from 73 maternity hospitals. Detailed reproductive
      histories were collected by interview a few weeks after the birth. The cases were
      603 women having a singleton birth between 20 and <32 weeks gestation (very
      preterm births including terminations of pregnancy). The controls were 796
      randomly selected women from the population having a singleton birth of at least
      37 completed weeks gestation. Unconditional logistic regression was used to
      assess the association of very preterm birth with sequence of pregnancies defined
      by their outcome (prior abortion - spontaneous or induced, and prior preterm or
      term birth) with adjustment for sociodemographic factors. The outcomes of each
      prior pregnancy, stratified by pregnancy order, and starting with the pregnancy
      immediately before the index or control pregnancy, were categorised as one of
      abortion, preterm birth or term birth. We showed that each of these prior
      pregnancy events was an independent risk of very preterm birth. This finding does
      not support the hypothesis of a neutralising effect of a term birth after an
      abortion on the subsequent risk for very preterm birth and is further evidence
      for the cumulative or increasing risk associated with increasing numbers of prior
      abortions or preterm births.

PMID- 20670223
TI  - The use of covariates to identify records with implausible gestational ages using
      the birthweight distribution.
AB  - The objective of this study was to evaluate the usefulness of covariates in
      identifying birth records with implausible values of gestational age. Birthweight
      distributions for births with early reported gestational ages are markedly
      bimodal, suggesting a mixture of two distributions. Most births form a normal
      shaped left-hand (primary) distribution and a smaller number form the right-hand
      (secondary) distribution. The births in the secondary distribution are thought to
      have gestational age mistakenly reported. Prior work has found that births in the
      secondary distribution are at higher risk of poor outcomes than those in the
      primary distribution. Using 2002 US Natality data for gestational ages 26-35
      weeks, we fit normal mixture models to birthweight with and without covariates
      (maternal race, education, parity, age, region of the country, prenatal care
      initiation) by reported gestational age. Additional models were stratified by
      infant sex. This approach allowed for the relationship between the covariates and
      birthweight to differ between the components. Mixture models fit reasonably well
      for reported gestational ages <33 weeks, but not for later weeks. Counter to the
      hypothesis, results were similar for models with and without covariates or
      stratification or both, although stratified models without covariates predicted
      slightly more girls and slightly fewer boys in the secondary distribution than
      did the corresponding unstratified models. For reported gestational ages <33
      weeks, predictions from the four sets of models were highly correlated and
      predictions were similar for subgroups defined by the clinical estimates of
      gestational age and other covariates. For births with reported gestational ages
      of 29 or more weeks, the proportion in the secondary distribution exceeded 30%,
      although this varied by maternal characteristics. The use of covariates and
      stratification complicated model fitting without materially improving
      identification of implausible gestational age values, supporting inferences from
      prior studies using data 'cleaned' without consideration of maternal or infant
      characteristics.

PMID- 20670224
TI  - Ovarian function and cigarette smoking.
AB  - Cigarette smoking has been implicated in reproductive outcomes including delayed
      conception, but mechanisms underlying these associations remain unclear. One
      potential mechanism is the effect of cigarette smoking on reproductive hormones;
      however, studies evaluating associations between smoking and hormone levels are
      complicated by variability of hormones and timing of specimen collection. We
      evaluated smoking among women participating in the BioCycle Study, a longitudinal
      study of menstrual cycle function in healthy, premenopausal, regularly
      menstruating women (n = 259). Fertility monitors were used to help guide timing
      of specimen collection. Serum levels of oestradiol, progesterone, follicle
      stimulating hormone (FSH), luteinising hormone (LH) and total sex-hormone binding
      globulin (SHBG) across phases of the menstrual cycle were compared between
      smokers and non-smokers. We observed statistically significant phase-specific
      differences in hormone levels between smokers and non-smokers. Compared with non
      smokers, smokers had higher levels of FSH in the early follicular phase and
      higher LH at menses after adjusting for potential confounding factors of age,
      race, body mass index, parity, vigorous exercise, and alcohol and caffeine intake
      through inverse probability of treatment weights. No statistically significant
      differences were observed for oestradiol, progesterone or SHBG. These phase
      specific differences in levels of LH and FSH in healthy, regularly menstruating
      women who are current smokers compared with non-smokers reflect one mechanism by
      which smoking may influence fertility and reproductive health.

PMID- 20670225
TI  - Disparities in the risk of gestational diabetes by race-ethnicity and country of
      birth.
AB  - Little information exists on the association between maternal country of birth
      and risk of gestational diabetes (GDM). We examined within each race-ethnicity
      group whether the risk of GDM differs between women born inside and outside the
      US. The study was a cohort study of 216 089 women who delivered an infant between
      1995 and 2004 with plasma glucose data from the screening 50-g glucose challenge
      test and the diagnostic 100-g, 3-h oral glucose tolerance test. The age-adjusted
      prevalence of GDM varied by race-ethnicity and was lowest for non-Hispanic white
      (4.1%) and highest among Asian Indians (11.1%). In multivariable models, being
      born outside of the US was associated with an increased risk of GDM among black,
      Asian Indian, Filipina, Pacific Islanders, Chinese, Mexicans and non-Hispanic
      white women, whereas, Japanese and Korean foreign-born women had a decreased risk
      of GDM. Clinicians should be aware that among certain race-ethnicity groups women
      born outside the US may be at increased risk of GDM and may warrant special
      preventive and culturally sensitive care.

PMID- 20670226
TI  - Wilms' tumour: a systematic review of risk factors and meta-analysis.
AB  - Wilms' tumour comprises 95% of all renal cancers among children less than 15
      years of age. The purpose of this review is to examine the existing literature on
      perinatal and environmental risk factors for Wilms' tumour. A search for
      epidemiological studies that examined risk factors for Wilms' tumour was
      undertaken in Medline, LILACS, ISI Web of Science and Dissertation Abstracts. A
      total of 37 studies, including 14 cohort, 21 case-control and 2 case-cohort
      studies, were identified that examined environmental and perinatal risk factors.
      Most studies were from Western Europe and North America, and among case-control
      studies, 16 used randomly selected population-based controls. We observed a
      significantly increased risk of Wilms' tumour with maternal exposure to
      pesticides prior to the child's birth (OR = 1.37 [95% CI 1.09, 1.73]), high
      birthweight (OR = 1.36 [95% CI 1.12, 1.64]) and preterm birth (OR = 1.44 [95% CI
      1.14, 1.81]), although the results regarding pesticide exposure may be subject to
      publication bias (Egger's test, P = 0.09). Further analyses to adjust for the
      heterogeneity in the results for high birthweight and preterm birth did not
      statistically change the significance of the results. Additionally, an increased
      though not statistically significant risk of Wilms' tumour was associated with
      maternal hypertension (OR = 1.30 [95% CI 0.99, 1.72]), and, compared with the
      first born, being a second or later birth was associated with a significantly
      decreased risk (OR = 0.82 [95% CI 0.71, 0.95]). This review suggests a role for
      several perinatal and environmental risk factors in the aetiology of Wilms'
      tumour.

PMID- 20670227
TI  - Fifty years of paediatric malignant bone tumours in the West Midlands, UK, 1957
      2006: incidence, treatment and outcome.
AB  - Malignant bone tumours in the paediatric age group (0-14 years) are uncommon;
      various aetiological theories exist and few reports of incidence, age and sex
      distributions have been published. We examined the incidence of childhood
      malignant bone tumours in one large single region of the UK over an extended
      period of 50 years. The West Midlands specialist regional children's tumour
      registry holds data on all malignancies and benign brain tumours in children
      under 15 years in the West Midlands region, which has a population of around 1
      million children. Demographic and clinical data have been abstracted and
      diagnoses reviewed by a panel of expert pathologists. During the period 1957
      2006, 259 cases of malignant paediatric bone tumours were diagnosed. There were
      153 osteosarcomas, 78 Ewing sarcomas and 28 other primary bone tumours. The
      overall age standardised rate was 4.66, with no increase over time, although
      there was a significant increase in the incidence of Ewing sarcomas in the period
      1965-92. Sixty-eight per cent of tumours were in patients over 10 years, whereas
      the incidence in patients under 10 years showed a non-significant increase.
      Survival rates increased dramatically post-chemotherapy introduction, with Ewing
      sarcoma demonstrating better survival overall. This is a large study giving an
      overview of malignant bone tumours in the childhood population of a single region
      over an extended period, showing results consistent with national reports. It
      also examines late effects, which were mostly mobility/orthopaedic, although
      almost one-fifth of patients had cardiac problems and five went on to develop
      second malignancies.

PMID- 20670228
TI  - Incidence and distribution of pathogens in early-onset neonatal sepsis in the era
      of antenatal antibiotics.
AB  - In 2001 France issued a new set of guidelines for the use of antenatal
      antibiotics (AA). These guidelines recommended intrapartum antimicrobial
      prophylaxis (IAP) to prevent group B streptococcal (GBS) disease and AA to
      prolong pregnancy in the event of preterm premature rupture of membranes (AA for
      PPROM). This study aims to determine the effects of AA, recommended by national
      guidelines, on the incidence and distribution of pathogens in early-onset
      neonatal sepsis (EONS). We performed a population-based, prospective,
      observational study of level II and III perinatal centres throughout the region
      of Alsace, a northeastern area of France, between March 2004 and February 2005.
      The study population included all neonates with confirmed or probable EONS, who
      were treated with antibiotics for at least 5 days. We analysed exposure to AA, as
      well as clinical and microbiological data obtained from medical records. A total
      of 20 131 neonates were born during the study period, and 217 were included in
      the study. Of these, 24 subjects had confirmed sepsis, 140 had probable sepsis
      and 53 had possible EONS. The overall incidence of confirmed EONS was 1.19 per
      1000 births. The infecting bacteria was GBS in 15 of 24 (62.5%) confirmed EONS
      cases (incidence: 0.75 per 1000 births) and in 81 of 140 (58%) probable sepsis
      cases. Escherichia coli was identified in 6 of 24 (25%) cases of confirmed EONS
      (incidence: 0.3 per 1000 births) and in 30 of 140 (21%) cases of clinical sepsis.
      Among E. coli infections (n= 36), amoxicillin resistance (n= 18) was
      statistically linked with AA use (P = 0.045). This link was significant in cases
      of PPROM (P = 0.015), but not when IAP was administered to prevent GBS disease (P
      = 0.264). IAP was not performed in 18 of 60 (30%) cases and 32 of 93 (34%) cases,
      despite positive screening or the presence of risk factors for EONS,
      respectively. Group B streptococcus remains the predominant pathogen in the era
      of AA. Aminopenicillin-resistant E. coli infections seem to be linked to
      prolonged AA in cases of PPROM and appear to preferentially affect preterm
      infants. Therefore, postnatal treatment strategies should consider this possible
      effect. Our data indicate that the current policy of GBS maternal prophylaxis is
      not associated with an excessive risk of pathogen resistance. Considering the
      high incidence of GBS EONS in our region, possible progress could result from
      better observance of guidelines. These results strengthen the need for
      continuation of surveillance.

PMID- 20670229
TI  - Maternal vaginal colonisation by Staphylococcus aureus and newborn acquisition at
      delivery.
AB  - We studied 1139 mother-infant pairs where the mother had had at least one vaginal
      swab in the month before delivery and their babies had had gastric and ear swabs
      taken immediately after delivery. The prevalence of vaginal carriage of
      Staphylococcus aureus was 5.9% among 1139 pregnant women within 1 month of
      delivery. The colonisation rate of S. aureus in newborns was tenfold higher when
      the mother was a vaginal carrier than when she was not (31.3% vs. 2.7%; relative
      risk 11.6 [95% CI 7.0, 19.2]; P < 0.05). Among carriers, delivery by caesarean
      section compared with the vaginal route, significantly decreased the likelihood
      of S. aureus colonisation in the newborns (15.4% vs. 41.5%; relative risk 0.35
      [95% CI 0.14, 0.98]; P < 0.03). No S. aureus colonisation was detected in the
      mothers of 58% of the colonised newborns suggesting extra-delivery colonisation
      routes. Consequences for newborns were unclear as only one case of S. aureus
      neonatal sepsis was observed.

PMID- 20670230
TI  - Effect of prenatal exposure to fine particulate matter on ventilatory lung
      function of preschool children of non-smoking mothers.
AB  - Impaired fetal development is associated with a number of adult chronic diseases
      and it is believed that these associations arise as a result of the phenomenon of
      prenatal programming, which involves persisting changes in structure and function
      of various body organs caused by ambient factors during critical and vulnerable
      periods of early development. The main goal of the study was to assess the
      association between lung function in early childhood and prenatal exposure to
      fine particulate matter (PM(2.5)), which represents a wide range of chemical
      compounds potentially hazardous for fetal development. Among pregnant women
      recruited prenatally to the study, personal measurements of PM(2.5) were
      performed over 48 h in the second trimester of pregnancy. After delivery, infants
      were followed for 5 years; the interviewers visited participants in their homes
      to record children's respiratory symptoms every 3 months in the child's first 2
      years of life and every 6 months thereafter. In the fifth year of the follow-up,
      children were invited for standard lung function testing of levels of forced
      vital capacity (FVC), forced expiratory volume in 1 s (FEV(1)) and forced
      expiratory volume in 0.5 s (FEV(0.5)). There were 176 children of non-smoking
      mothers, who performed at least two acceptable spirometry measurements.
      Multivariable linear regression showed a significant deficit of FVC at the
      highest quartile of PM(2.5) exposure (beta coefficient = -91.9, P = 0.008), after
      adjustment for covariates (age, gender, birthweight, height and wheezing). Also
      FEV(1) level in children was inversely correlated with prenatal exposure to
      PM(2.5), and the average FEV(1) deficit amounted to 87.7 mL (P = 0.008) at the
      higher level of exposure. Although the effect of PM(2.5) exposure on FEV(0.5) was
      proportionally weaker (-72.7, P = 0.026), it was also statistically significant.
      The lung function level was inversely and significantly associated with the
      wheezing recorded over the follow-up. The findings showed that significant lung
      function deficits in early childhood are associated with prenatal exposure to
      fine particulate matter, which may affect fetal lung growth.

PMID- 20670231
TI  - Increased risk of orofacial clefts associated with maternal obesity: case-control
      study and Monte Carlo-based bias analysis.
AB  - Our objective was to evaluate whether infants born to obese or diabetic women are
      at higher risk of non-syndromic orofacial clefting. We conducted a population
      based case-control study using Washington State birth certificate and
      hospitalisation data for the years 1987-2005. Cases were infants born with
      orofacial clefts (n = 2153) and controls infants without orofacial clefts (n = 18
      070). The primary exposures were maternal obesity (body mass index > or =30) and
      diabetes (either pre-existing or gestational). We estimated adjusted odds ratios
      (ORs) to compare, for mothers of cases and controls, the proportions of obese vs.
      normal-weight women and diabetic vs. non-diabetic women. We additionally
      performed Monte Carlo-based simulation analysis to explore possible influences of
      biases. Obese women had a small increased risk of isolated orofacial clefts in
      their offspring compared with normal-body mass index women [adjusted OR 1.26; 95%
      confidence interval 1.03, 1.55]. Results were similar regardless of type of
      cleft. Bias analyses suggest that estimates may represent underlying ORs of
      stronger magnitude. Results for diabetic women were highly imprecise and
      inconsistent. We and others have observed weak associations of similar magnitude
      between maternal obesity and risk of non-syndromic orofacial clefts. These
      results could be due to bias or residual confounding. However, it is also
      possible that these results represent a stronger underlying association. More
      precise exposure measurement could help distinguish between these two
      possibilities.

PMID- 20670232
TI  - Improving quality in anesthesia: where are we starting from and how are we going
      to get there?

PMID- 20670233
TI  - Quality in pediatric anesthesia.

PMID- 20670234
TI  - The effects of mivacurium-induced neuromuscular block on Bispectral Index and
      Cerebral State Index in children under propofol anesthesia - a prospective
      randomized clinical trial.
AB  - BACKGROUND: In adults anesthetized with propofol, muscle relaxants may decrease
      the Bispectral Index (BIS). The aim of this prospective randomized trial was to
      detect the influence of a muscle relaxant bolus on the BIS and the Cerebral State
      Index (CSI) in children under propofol anesthesia. METHODS: Forty pediatric
      patients, age 6.6 +/- 3.3 years, weight 24 +/- 9 kg, scheduled for surgical
      procedures requiring general anesthesia were enrolled. Two minutes after i.v.
      injection of 0.3 mcg.kg(-1) of sufentanil, general anesthesia was induced by an
      initial bolus of 3 mg.kg(-1) of propofol, followed by a continuous infusion
      titrated to achieve a stable BIS value of 50 +/- 5. Patients received either
      mivacurium 0.25 mg.kg(-1) (Group Miva) or NaCl 0.9% 0.12 ml.kg(-1) (Group
      Control). Mean BIS and CSI values per minute were compared between (Miva vs.
      Control) and within groups (Baseline vs 5 min. after study drug administration).
      RESULTS: The observed changes in BIS and CSI values before and after
      administration of study drugs revealed no differences between the study groups.
      Mean baseline BIS and CSI values were lower than 5 min after study drug
      administration. There were no intergroup differences with respect to BIS and CSI
      values at any time point. CONCLUSIONS: These data suggest that in pediatric
      patients anesthetized with propofol, administration of mivacurium has no impact
      on BIS and CSI values.

PMID- 20670235
TI  - An institutional experience with epidural analgesia in children and young adults
      undergoing cardiac surgery.
AB  - BACKGROUND: Allowing spontaneous respiration after cardiac surgery eliminates
      complications related to mechanical ventilation and optimizes cardiopulmonary
      interaction. Epidural analgesia has been proposed to promote early extubation
      after cardiac surgery. OBJECTIVE: To identify the characteristics of patients
      with epidural analgesia and safety profiles with respect to the timing of
      extubation following cardiac surgery. DESIGN AND METHOD: A retrospective chart
      review of patients who underwent cardiac surgery during a 5-year period.
      Demographic, procedural, and perioperative variables were analyzed to investigate
      factors that affect the timing of extubation. RESULTS: A total of 750 records
      were reviewed. The patients' median age was 12 months, and 52% were infants (<1
      year). Seventy-five percent of the patients utilized cardiopulmonary bypass. The
      study population was classified into three groups according to the timing of
      extubation: 66% were extubated in the operating room or upon arrival at the PICU
      (Immediate), 15% were extubated within 24 h (mean, 10.8 h; 95% CI, 9.0-12.6)
      (Early), and 19% were extubated after 24 h (Delayed). For the Immediate and Early
      groups, multivariate logistic regression identified young age, increased cross
      clamp time, and inotrope score as independent risk factors for the need for
      mechanical ventilation. Postextubation respiratory acidosis (mean P(a)CO(2), 50
      mmHg; 95% CI, 49-51) was well tolerated by all patients. There were no neurologic
      complications related to the epidural technique. CONCLUSION: Epidural analgesia
      in children undergoing cardiac surgery provides stable analgesia without
      complications in our experience.

PMID- 20670236
TI  - Efficacy of palatal block for analgesia following palatoplasty in children with
      cleft palate.
AB  - BACKGROUND: This prospective randomized controlled study was undertaken to
      evaluate the efficacy of palatal block i.e. blocking of naso palatine, greater
      and also lesser palatine nerves in children with cleft palate undergoing
      palatoplasty by evaluating its effects on intraoperative anesthetic requirement,
      postoperative analgesia and parental satisfaction. METHODS: Forty-five pediatric
      patients aged below five undergoing cleft palate repair were randomly allocated
      to three groups of 15 each. After tracheal intubation, Group NB received no block
      for control, group S received 0.5 ml of normal saline and group B received 0.5 ml
      of 0.25% bupivacaine for palatal block. Postoperative pain score, the time to
      first demand of analgesia and number of rescue analgesic demands were noted.
      Finally, the parental satisfaction was graded. RESULTS: The block had no
      anesthetic sparing effect. The mean pain scores were significantly lower in
      patients who received block than in the group NB. The mean area under curve for
      FLACC score in group NB was 29 with 95% CI of 25-32, group S was 15 with 95% CI
      of 8.9-22.3 and in group B, it was 10 with 95% CI of 6-14. The time to first
      demand of analgesia was 6 [4.5-6] h in group NB, 18 [6-18] h in group S and 18
      [18-18] h in group B (P-0.000). The number of demands of rescue analgesia was
      significantly less in group B 0 [0-0.25], 0 [0-2] in S group compared to group NB
      3 [3-3] (P-0.000). The parental satisfaction was good in patients who received
      block and poor in group NB. CONCLUSION: Palatal block is technically simple, safe
      and effectively provides postoperative analgesia with good parental satisfaction.
      Injection of saline also produced palatal nerve block; however, the effect was
      not consistent.

PMID- 20670237
TI  - A novel isotonic-balanced electrolyte solution with 1% glucose for perioperative
      fluid management in children- an animal experimental preauthorization study.
AB  - BACKGROUND: The recommendations for perioperative maintenance fluid in children
      have been adapted from hypotonic to isotonic electrolyte solutions with lower
      glucose concentrations (1-2.5% instead of 5%) to avoid hyponatremia or
      hyperglycemia. OBJECTIVE: The objective of this prospective animal study was to
      determine the margin of safety of a novel isotonic-balanced electrolyte solution
      with 1% glucose (BS-G1) in comparison with normal saline with 1% glucose (NS-G1)
      in the case of accidental hyperhydration with a focus on acid-base electrolyte
      balance, glucose concentration, osmolality and intracranial pressure in piglets.
      METHODS: Ten piglets (bodyweight 11.8 +/- 1.8 kg) were randomly assigned to
      receive either 100 ml.kg(-1) of BS-G1 or NS-G1 within one hour. Before, during
      and after fluid administration, electrolytes, lactate, hemoglobin, hematocrit,
      glucose, osmolality and acid-base parameters were measured. RESULTS: Unlike BS
      G1, administration of NS-G1 produced mild hyperchloremic acidosis (base excess BS
      G1 vs NS-G1, baseline 1.9 +/- 1.7 vs 2.9 +/- 0.9 mmol.l(-1), study end 0.2 +/-
      1.7 vs -2.7 +/- 0.5 mmol.l(-1), P < 0.05, chloride BS-G1 vs NS-G1 baseline 102.4
      +/- 3.4 vs 102.0 +/- 0.7 mmol.l(-1), study end 103.4 +/- 1.8 vs 109.0 +/- 1.4
      mmol.l(-1)P < 0.05). The addition of 1% glucose led to moderate hyperglycemia (P
      < 0.05) with a concomitant increase in serum osmolality in both groups (P <
      0.05). CONCLUSION: Both solutions showed a wide margin of safety in the case of
      accidental hyperhydration with less acid-base electrolyte changes when using BS
      G1. This novel solution could therefore enhance patient's safety within the scope
      of perioperative volume management.

PMID- 20670238
TI  - Pediatric anesthesia in developing countries: experience in the two main
      university hospitals of Benin in West Africa.
AB  - AIMS: To describe the practice of pediatric anesthesia in the main University
      Hospitals in Benin. PATIENTS AND METHODS: We conduct a retrospective study
      involving 512 children at the 'Centre National Hospitalier et Universitaire' and
      the 'Hopital de la Mere et de l'Enfant Lagune' in Cotonou. All children less than
      15 years of age undergoing surgery from January to December 2007 were included.
      Patient demographics, anesthetic technique, perioperative monitoring and
      complications were analyzed. RESULTS: General anesthesia was used in 94% of
      children. Regional anesthesia was used in 1.7% of children at CNHU and 17% of
      children at Hopital de la Mere et de l'Enfant Lagune. Inhalational induction was
      the commonest technique used. Halothane was the only inhalational agent available
      for induction. Seventy-two percent of children having general anesthesia were
      intubated. Muscle relaxation was used in 48% of cases, only with pancuronium. The
      available perioperative monitoring equipment was not used regularly. All children
      having general anesthesia breathed spontaneously with manual assistance. There
      were eight cardiac arrests recorded, giving an incidence of 156 cardiac arrests
      per 10,000 anesthetics. Hypoxia was the commonest cause of cardiac arrest. The
      mortality associated with cardiac arrest was very high (62%). There were three
      prognostic factors that predicted a poor outcome: age <1 year, emergency surgery
      and an ASA score of three or more. CONCLUSION: Pediatric anesthesia in the two
      University Hospitals is far from satisfactory. Morbidity and mortality are
      unacceptably high. Suggestions are made to improve the safety of children
      undergoing anesthesia.

PMID- 20670239
TI  - Supplementing desflurane with intravenous anesthesia reduces fetal cardiac
      dysfunction during open fetal surgery.
AB  - OBJECTIVE: To lower the incidence and severity of fetal cardiovascular depression
      during maternal fetal surgery under general anesthesia. AIM: We hypothesized that
      supplemental intravenous anesthesia (SIVA) with propofol and remifentanil would
      lower the need for high-dose inhalational anesthesia and provide adequate
      maternal depth of anesthesia and uterine relaxation. SIVA technique would
      minimize prolonged fetal exposure to deep inhalational anesthetics and
      significant intraoperative fetal cardiovascular depression. BACKGROUND: Fetal
      hypoxia and significant fetal hemodynamic changes occur during open fetal surgery
      because of the challenges such as surgical manipulation, hysterotomy, uterine
      contractions, and effects of anesthetic drugs. Tocolysis, a vital component of
      fetal surgery, is usually achieved using volatile anesthetic agents. High
      concentrations of volatile agents required to provide an appropriate degree of
      uterine relaxation may cause maternal hypotension and placental hypoperfusion, as
      well as direct fetal cardiovascular depression. METHODS: We reviewed medical
      records of 39 patients who presented for ex utero intrapartum treatment and mid
      gestation open fetal surgery between April 2004 and March 2009. Out of 39
      patients, three were excluded because of the lack of echocardiographic data; 18
      patients received high-concentration desflurane anesthesia and 18 patients had
      SIVA with desflurane for uterine relaxation. We analyzed the following data:
      demographics, fetal medical condition, anesthetic drugs, concentration and
      duration of desflurane, maternal arterial blood pressure, intraoperative fetal
      echocardiogram, presence of fetal bradycardia, and need for intraoperative fetal
      resuscitation. RESULTS: Adequate uterine relaxation was achieved with about 1.5
      MAC of desflurane in the SIVA group compared to about 2.5 MAC in the desflurane
      only anesthesia group (P = 0.0001). More fetuses in the high-dose desflurane
      group compared to the SIVA group developed moderate-severe left ventricular
      systolic dysfunction over time intraoperatively (P = 0.02). 61% of fetuses in the
      high-dose desflurane group received fetal resuscitative interventions compared to
      26% of fetuses in the SIVA group (P = 0.0489). CONCLUSION: SIVA as described
      provides adequate maternal anesthesia and uterine relaxation, and it allows for
      decreased use of desflurane during open fetal surgery. Decreased use of
      desflurane may better preserve fetal cardiac function.

PMID- 20670240
TI  - Study to assess the laryngeal and pharyngeal spread of topical local anesthetic
      administered orally during general anesthesia in children.
AB  - BACKGROUND: Topical local anesthesia of the airway of anaesthetized children has
      many potential benefits. In our institution, lignocaine is topically instilled
      blindly into the back of the mouth with the expectation that it will come into
      contact with the larynx. The volume and method of application varies between
      clinicians. There is no published evidence to support the plausibility of this
      technique. AIM: To determine whether this technique of instillation results in
      the local anesthetic coming into contact with key laryngeal structures and
      whether this is influenced by volume or additional physical maneuvers.
      METHODS/MATERIALS: Sixty-three healthy anaesthetized children between 6 months
      and 16 years old had lignocaine stained with methylene blue poured into the back
      of their mouths. The volume and subsequent physical maneuver were determined by
      randomization. A blinded observer assessed staining of the vocal cords,
      epiglottis, vallecula and piriform fossae by direct laryngoscopy. Airway
      complications were recorded. RESULTS: Fifty-three of the 63 children had complete
      staining of all four areas. Four children had one area unstained, and all others
      had at least partial staining of all four structures. Nine children coughed
      following induction of anesthesia. Coughing was more likely in children with
      incomplete staining (P = 0.03), low volume lignocaine (P = 0.003) and following a
      head lift (P = 0.02). CONCLUSION: Oral administration of lignocaine without use
      of a laryngoscope frequently results in widespread coverage of key laryngeal
      structures and may reduce the risk of coughing.

PMID- 20670241
TI  - Ventricular fibrillation in an ex-premature neonate following reperfusion of
      ischemic gut incarcerated within an inguinal hernia.
AB  - We describe the case of a neonate who underwent surgery for bowel obstruction.
      The child was born at 25 weeks postconception, and at the time of surgery, he had
      a postconceptual age of 44 weeks. He had undergone two previous laparotomy
      procedures for necrotizing enterocolitis. At laparotomy, there was unexpected
      extensive compromise to gut perfusion. The child developed ventricular
      fibrillation following the reperfusion of a segment of ischemic gut found
      incarcerated in an inguinal hernial orifice. We discuss the pathophysiology of
      intestinal ischemia-reperfusion (I-R) injury. We have reviewed the interventions
      that may be employed to minimize the systemic impact of I-R.

PMID- 20670242
TI  - An appreciation of Robert Moors Smith MD, an icon of pediatric anesthesiology.
AB  - Robert Moors Smith M.D. passed away recently at the age of 97. During his
      chairmanship of the Department of Anesthesiology at Children's Hospital Boston
      from 1946 to 1980 he gained world prominence for his contributions to the
      anesthetic care of children and the education of generations of pediatric
      anesthesiologists. His dedicated and earnest approach, reflected in tribute and
      in his own words, provide a window on pediatric anesthesia during its development
      into a recognized subspecialty in the 20th century.

PMID- 20670243
TI  - Anesthetic management of a rare case of Shprintzen-Goldberg craniosynostosis
      syndrome.

PMID- 20670244
TI  - Perioperative anesthetic concerns in a child with systemic onset juvenile
      idiopathic arthritis syndrome.

PMID- 20670245
TI  - Intermittent single lung ventilation in a 620-gram micropremie during
      postintubation carinal laceration repair.

PMID- 20670246
TI  - Routine use of ultrasound to guide internal jugular vein access in children.

PMID- 20670247
TI  - Comments on comparison of Bonfils fiberscope-assisted laryngoscopy with standard
      direct laryngoscopy in simulated difficult pediatric intubation.

PMID- 20670249
TI  - Placement of an US-guided supraclavicular block postoperatively in children: can
      we make this easy?

PMID- 20670250
TI  - Re: orotracheal to nasotracheal intubation exchange in pediatric patients with a
      difficult airway.

PMID- 20670251
TI  - Re: undiagnosed systemic mastocytosis in a teenager revealed during general
      anesthesia.

PMID- 20670252
TI  - Barotrauma: a life-threatening complication of fiberoptic endotracheal intubation
      in a neonate.

PMID- 20670254
TI  - Challenges and advances in veterinary cardiology.

PMID- 20670255
TI  - Canine dilated cardiomyopathy: a retrospective study of prognostic findings in
      367 clinical cases.
AB  - OBJECTIVE: To review the association between clinical signs and diagnostic
      findings and the survival time of dogs with dilated cardiomyopathy (DCM), and any
      influence of treatment prescribed. METHODS: A retrospective observational study
      of 367 dogs with DCM. Survival times until death or euthanasia for cardiac
      reasons were analysed using the Kaplan-Meier method plus univariate and
      multivariate Cox proportional hazards models. Two-tailed P values less than 0.05
      were considered statistically significant. RESULTS: In the multivariate model,
      left ventricular diameter (LVDs)-index (P=0.0067), presence of pulmonary oedema
      on radiography (P=0.043), presence of ventricular premature complexes (VPCs)
      (P=0.0012), higher plasma creatinine (P=0.0002), lower plasma protein (P=0.029)
      and great Dane breed (P=0.0003) were negatively associated with survival. Most
      dogs were treated with angiotensin-converting enzyme inhibitors (93%) or
      furosemide (86%), and many received digoxin (50%) and/or pimobendan (30%).
      Thirteen dogs were lost to follow-up. No conclusions could be made in this study
      on the association between use of drugs and survival. CLINICAL SIGNIFICANCE: The
      LVDs-index was the single best variable for assessing the prognosis in this group
      of dogs with DCM. Other variables that were negatively associated with survival
      were presence of pulmonary oedema on radiography, presence of VPCs, higher plasma
      creatinine, lower plasma protein and great Dane breed.

PMID- 20670256
TI  - Saliva crystallisation as a means of determining optimal mating time in bitches.
AB  - OBJECTIVES: To chart saliva crystallisation patterns throughout pro-oestrus and
      oestrus in bitches, and to assess their reliability as a tool for optimising the
      timing of breeding. METHODS: Six beagle bitches with normal reproductive activity
      were used. Saliva ferning patterns were established during pro-oestrus and
      oestrus. Vaginal cytology, progesterone (P4) levels and behavioural signs were
      used to determine the optimum mating time. Receiver operating characteristic
      (ROC) analysis was performed. RESULTS: Different ferning patterns were scored
      from 0 to 2. Although variations in saliva crystallisation were noted during the
      follicular phase of the oestrous cycle in bitches, the test did not prove
      accurate; test sensitivity was 40.6%, i.e. too low to reliably discriminate the
      fertile period, while specificity was 86.1%. CLINICAL SIGNIFICANCE: This test
      could be used to complement other methods of determining the fertile period in
      bitches, but its potential capacity remains to be demonstrated.

PMID- 20670257
TI  - Contrast-enhanced magnetic resonance angiography of patent ductus arteriosus in a
      dog.
AB  - Gadolinium-enhanced three-dimensional magnetic resonance angiography is a
      relatively new technique in the veterinary field. A mature dog with suspected
      patent ductus arteriosus underwent contrast-enhanced magnetic resonance
      angiography at 1.0 T with a three-dimensional fast low-angle shot (FLASH)
      gradient-echo technique. Qualitatively, three-dimensional images of the ductus
      were particularly clear with surface reconstructions, and ductus diameters were
      easy to assess in native images. Contrast-enhanced magnetic resonance angiography
      is a fast, relatively non-invasive procedure that could be particularly useful
      when non-surgical interventional procedures are anticipated for ductus occlusion.

PMID- 20670263
TI  - A look back--AANP is a 25-year-old!

PMID- 20670264
TI  - The primary care nurse practitioner and cancer survivorship care.
AB  - PURPOSE: To examine the important role that primary care nurse practitioners
      (NPs) have in providing long-term surveillance and health maintenance for breast,
      prostate, and colorectal cancer survivors throughout the continuum of cancer
      care. DATA SOURCES: MEDLINE, CINAHL, MD-Consult, and Cochrane's databases were
      utilized with the inclusion of primary research and critical research reviews
      from January 1995 through March 2008. Select organizational websites were also
      cited. CONCLUSIONS: Cancer patients experience changes in the focus of their care
      when management shifts from the treatment of cancer to management of treatment
      side effects and outcomes, to survivorship care, and to secondary cancer
      treatment. NPs have a strong impact on cancer survivorship care by serving in
      various roles and settings throughout the cancer trajectory to improve patient
      outcomes. IMPLICATIONS FOR PRACTICE: Cancer survivorship care expands beyond
      specialty settings, into primary care. NPs have a key role in ensuring continuity
      of care for patients with cancer. Models of care that promote continuity and high
      quality of care for patients with cancer include the shared-care and nurse
      managed health center models. The formal collaborative plan of care is essential
      in long-term cancer survivorship care.

PMID- 20670265
TI  - Transsexual primary care.
AB  - PURPOSE: Transsexual presentations in primary care stress mainstream health care
      physical resources, institutional organization, and the cultural flexibility of
      providers and interdisciplinary staff. This article describes the ethical
      landscape, examines gender identity culture, and considers gender reassignment
      physiology. Nurse practitioners are challenged to advocate for this population.
      DATA SOURCES: Sources for the discussion derive from published institutional
      guidelines, institutional and civic policies, web-based information in the public
      domain, and professional journal articles. CONCLUSIONS: Advocacy for cultural
      sensitivity, institutional policy change,and professional integrity will
      determine healthcare quality for this population. Advocacy for cultural awareness
      and institutional change has begun in larger institutions and metropolitan areas,
      but is necessary across primary care settings. IMPLICATIONS FOR PRACTICE: Caring
      for transsexuals requires knowledge of anatomical reassignments, hormonal therapy
      effects, and cultural sensitivities particular to the gender identity community.
      Healthcare screening and physical exam modifications for these presentations
      require forethought and appropriate adjustments.

PMID- 20670266
TI  - Comparison of nurse practitioner job core competency expectations of nurse
      managers, nurse practitioners, and physicians in Taiwan.
AB  - PURPOSE: The purpose of this study was to compare expectations of nurse
      practitioner (NP) job competencies among physicians, nurse managers, and NPs.
      DATA SOURCES: A quantitative survey was designed using the Analytic Hierarchy
      Process to determine the essential NP job competencies based on a checklist of 38
      daily activities of NPs, which were recorded for a 10-day period. Using purposive
      sampling, a demographic data tool and a Nurse Practitioner Job Competency
      Questionnaire were completed by 56 participants from 13 hospitals in Taiwan, for
      which they prioritized and assigned percentage weights for NP competencies. A
      qualitative open-ended interview was undertaken to establish the meaning of the
      hierarchy outcomes that had been obtained. CONCLUSIONS: NPs face the pressure of
      whether medical staff and nurses agree with NPs' perceptions of their role, which
      can result in conflicts between nurses and doctors. Taiwanese NPs are still seen
      as assistants to doctors and, as such, the benefits of the creation of this new
      field of nursing are not being fully utilized. IMPLICATIONS FOR PRACTICE: NPs
      should be aware of discrepancies among health professionals as to their role,
      make efforts to communicate what their competencies include to avoid conflicts,
      and use their abilities effectively.

PMID- 20670267
TI  - An innovative approach to standardizing heart failure care: the heart failure
      support team.
AB  - PURPOSE: The purpose of this project was to determine if a comprehensive program
      of heart failure support using a three-step approach during acute care led by an
      advanced practice nurse (APN) improves outcomes. The goal was to implement
      Centers for Medicare and Medicaid Services (CMS) appropriate care recommendations
      for all patients with heart failure, reducing variation, and increasing quality
      of care. DATA SOURCES: Retrospective hospital chart reviews demonstrated patients
      were being admitted with one diagnosis, but ultimately discharged under the heart
      failure diagnosis-related group (DRG). Because these patients had not been
      identified as heart failure patients during hospitalization, we discovered an
      opportunity to improve care through program development. CONCLUSIONS: Once this
      approach was implemented consistently and sustained, we achieved near-perfect CMS
      scores. Composite quality scores for patients with heart failure improved from
      82.12% to 100%. Electronic tracking of patients after referrals from multiple
      sources became the keystone of the program, facilitating early identification,
      teaching, and ongoing patient monitoring. IMPLICATIONS FOR PRACTICE: A
      comprehensive approach to heart failure support using a team is recommended.
      However, research is needed to determine if this approach improves quality of
      life, hospital readmission rates, or lengths of stay for this vulnerable
      population.

PMID- 20670268
TI  - Correlating family nurse practitioners' perspectives of adult ADD/ADHD with
      employed pharmacotherapy: a pilot study.
AB  - PURPOSE: This study explores how family nurse practitioners (FNPs) in the state
      of Washington view adulthood attention deficit disorder/attention deficit
      hyperactivity disorder (ADD/ADHD) and how these views affect the pharmacotherapy
      FNPs employ. DATA SOURCES: A confidential survey containing 30 questions was
      mailed to self-selected FNPs who practice in the state of Washington (N= 126).
      Descriptive and Kendall's rank correlations coefficient statistical methods were
      used for data analysis. CONCLUSIONS: The majority of respondents do not hold
      negative views toward adults with ADD/ADHD and are aware that their personal
      views may affect how they treat the disorder. Most of the respondents agreed that
      given the likelihood of co-morbidity of adult ADD/ADHD, it can be a challenge to
      diagnose the disorder. The predominant prescribed medications for adult ADD/ADHD
      are consistent with current pediatric guidelines, with the exception of
      buproprion, which was identified by 40% of the respondents as either their
      primary or secondary drug of choice for treating adult ADD/ADHD. IMPLICATIONS FOR
      PRACTICE: Research effort needs to focus on the efficacy of buproprion for
      treating ADD/ADHD in adults. Moreover, exploration of the effectiveness of
      current pediatric guidelines to treat ADD/ADHD in adults must be assessed.

PMID- 20670269
TI  - Does familiarity breed respect? Physician attitudes toward nurse practitioners in
      a medically underserved state.
AB  - PURPOSE: An evolving primary care environment underscores the importance of
      physician and nurse practitioner (NP) interactions. We analyze how physician
      characteristics and close working relationships (presence of NPs in practice)
      influence physicians' attitudes toward NPs. DATA SOURCES: Bivariate analyses of
      2007-2008 Mississippi Physician Workforce Study survey data (response rate 23.3%)
      identified Mississippi physician characteristics associated with having NPs in
      practices and discrete NP-attitudinal items. Generalized physician attitudes
      toward NPs were modeled using multivariate regression. CONCLUSIONS: Generalists,
      physicians in public sector employment and physicians in larger practices are
      more likely to work in practices that also include NPs. Physicians working with
      NPs are somewhat younger than those who do not. Regression analysis indicates
      that male physicians had less-positive attitudes toward NPs, while physicians who
      practice alongside NPs and who have been in practice longer have the most
      positive generalized attitudes toward NPs. IMPLICATIONS FOR PRACTICE: Physicians
      who work in the same practice with NPs have more positive attitudes toward them.
      However, regardless of work arrangements, MS physicians are reluctant for NPs to
      practice independently. Physicians with early collaborative training with NPs may
      have more positive attitudes, but even such exposure will not necessarily lead
      physicians to support NPs' independent practice.

PMID- 20670270
TI  - Evaluation and treatment of depression in patients with heart failure.
AB  - PURPOSE: The purpose of this article is to provide an overview of relevant
      clinical issues including pathophysiology, clinical presentation,
      assessment/diagnosis, and treatment strategies regarding depression in the heart
      failure (HF) patient. This information was synthesized to create a clinical
      protocol to guide the practitioner in identifying, diagnosing, and treating
      depression in adult HF patients. This protocol was designed for use in the
      primary care or HF clinic setting. DATA SOURCES: PubMed and CINAHL were utilized
      to search for articles pertaining to HF and depression. CONCLUSIONS: The presence
      of depression in HF is associated with a worsening prognosis, increased risk of
      death, rehospitalization, and functional decline. The practitioner must identify
      predisposing factors for depression and evaluate symptoms. Self-rated screening
      instruments can assist the practitioner in identifying those with depression.
      Evidence is lacking regarding the treatment of depression in HF but selective
      serotonin reuptake inhibitors are likely the best option. IMPLICATIONS FOR
      PRACTICE: Understanding depression as it occurs in patients with HF is critical.
      If depression is identified and properly managed it may lead to better patient
      outcomes.

PMID- 20670271
TI  - Diagnosing myelodysplastic/myeloproliferative neoplasms: laboratory testing
      strategies to exclude other disorders.
AB  - INTRODUCTION: The 2008 World Health Organization classification of myeloid
      neoplasms includes the diagnostic category, myelodysplastic/myeloproliferative
      neoplasms (MDS/MPN), which encompasses those rare clonal myeloid proliferations
      that at initial presentation, show overlapping myeloproliferative and
      myelodysplastic features, making classification as either a myelodysplastic
      syndrome (MDS) or myeloproliferative neoplasm (MPN) problematic. There are four
      main subcategories, chronic myelomonocytic leukemia (CMML), atypical chronic
      myeloid leukemia, BCR-ABL1-negative (aCML), juvenile myelomonocytic leukemia
      (JMML), and myelodysplastic/myeloproliferative neoplasm, unclassifiable (MDS/MPN
      U), which also includes the provisional entity, refractory anemia with ring
      sideroblasts associated with marked thrombocytosis (RARS-T). Notably, the
      morphological features typical of MDS/MPNs are not specific and can be seen in
      other myeloid neoplasms at presentation or as part of disease progression or
      transformation. METHODS AND RESULTS: This review presents a laboratory approach
      to diagnosing MDS/MPNs in adults that allows for the exclusion of other disorders
      that may be otherwise indistinguishable. Ancillary studies including
      cytochemistry, immunohistochemistry, flow cytometry, and genetic testing are
      discussed. CONCLUSION: The most appropriate classification of myeloid neoplasms
      presenting with hybrid myelodysplastic/myeloproliferative features requires a
      comprehensive clinical and laboratory assessment with careful integration of the
      morphological, immunophenotypic, genetic, and clinical characteristics.

PMID- 20670272
TI  - Sciatic nerve injury from intramuscular injection: a persistent and global
      problem.
AB  - BACKGROUND/AIMS: An intramuscular (i.m.) injection into the buttock risks
      damaging the sciatic nerve. Safe injection practices need to be understood by
      doctors and nurses alike. The aims of this study were to determine if sciatic
      nerve injury because of i.m. injection is a continuing problem and to establish
      the availability of published guidelines on i.m. injection techniques. METHODS:
      Intramuscular injection related sciatic nerve injury claims to the New Zealand
      Accident Compensation Corporation between July 2005 and September 2008 were
      reviewed. Nursing organisations were surveyed to enquire about guidelines on i.m.
      injection. I.m. injection related sciatic nerve injuries in the medical and
      medicolegal literature (1989-2009) were systematically reviewed. RESULTS: There
      were eight claims for sciatic nerve injection injury made to the ACC during the 3
      year study period; all were in young adults. Only one of the nursing
      organisations contacted had published guidelines on i.m. injection technique, and
      these related specifically to immunisation. Seventeen reports of patients with
      sciatic nerve injury from i.m. injection were identified comprising a total of
      1506 patients, at least 80% of which were children. Nine court decisions finding
      in favour of the plaintiff were identified, all from the North American legal
      system. A broad range of drugs were implicated in the offending i.m. injections.
      CONCLUSIONS: Sciatic nerve injury from an i.m. injection in the upper outer
      quadrant of the buttock is an avoidable but persistent global problem, affecting
      patients in both wealthy and poorer healthcare systems. The consequences of this
      injury are potentially devastating. Safer alternative sites for i.m. injection
      exist. These should be promoted more widely by medical and nursing organisations.

PMID- 20670274
TI  - Selective autophagy regulates various cellular functions.
AB  - Autophagy is a self-eating system conserved among eukaryotes, in which cellular
      components including organelles are entrapped into a double membrane structure
      called the autophagosome and then degraded by lysosomal hydrolases. In addition
      to its role in supplying amino acids in response to nutrient starvation,
      autophagy is involved in quality control to maintain cell health. Thus,
      inactivation of autophagy causes the formation of cytoplasmic protein inclusions,
      which comprise misfolded proteins and the accumulation of many degenerated
      organelles, resulting in liver injury, diabetes, myopathy and neurodegeneration.
      Furthermore, although autophagy has been considered nonselective, increasing
      evidence points to the selectivity of autophagy in sorting vacuolar enzymes and
      removal of aggregate-prone proteins and unwanted organelles. Such selectivity
      allows diverse cellular regulation, similar to the ubiquitin proteasome pathway.
      In this review, we discuss the physiological roles of selective autophagy and
      their molecular mechanisms.

PMID- 20670273
TI  - Generating induced pluripotent stem cells from common marmoset (Callithrix
      jacchus) fetal liver cells using defined factors, including Lin28.
AB  - Although embryonic stem (ES) cell-like induced pluripotent stem (iPS) cells have
      potential therapeutic applications in humans, they are also useful for creating
      genetically modified human disease models in nonhuman primates. In this study, we
      generated common marmoset iPS cells from fetal liver cells via the retrovirus
      mediated introduction of six human transcription factors: Oct-3/4, Sox2, Klf4, c
      Myc, Nanog, and Lin28. Four to five weeks after introduction, several colonies
      resembling marmoset ES cells were observed and picked for further expansion in ES
      cell medium. Eight cell lines were established, and validation analyses of the
      marmoset iPS cells followed. We detected the expression of ES cell-specific
      surface markers. Reverse transcription-PCR showed that these iPS cells expressed
      endogenous Oct-3/4, Sox2, Klf4, c-Myc, Nanog and Lin28 genes, whereas all of the
      transgenes were silenced. Karyotype analysis showed that two of three iPS cell
      lines retained a normal karyotype after a 2-month culture. Both embryoid body and
      teratoma formation showed that marmoset iPS cells had the developmental potential
      to give rise to differentiated derivatives of all three primary germ layers. In
      summary, we generated marmoset iPS cells via the transduction of six
      transcription factors; this provides a powerful preclinical model for studies in
      regenerative medicine.

PMID- 20670275
TI  - Diversity of the cagA gene of Helicobacter pylori strains from patients with
      gastroduodenal diseases in the Philippines.
AB  - Helicobacter pylori CagA protein is considered a major virulence factor
      associated with gastric cancer. There are two major types of CagA proteins: the
      Western and East Asian CagA. The East Asian CagA-positive H. pylori infection is
      more closely associated with gastric cancer. The prevalence of gastric cancer is
      quite low in the Philippines, although Philippine populations are considered to
      originate from an East Asia source. This study investigates the characteristics
      of the cagA gene and CagA protein in Philippine H. pylori strains and compares
      them with previously characterized reference strains worldwide. The full-length
      cagA gene was sequenced from 19 Philippine isolates and phylogenetic
      relationships between the Philippine and 40 reference strains were analyzed. All
      Philippine strains examined were cagA positive, and 73.7% (14/19) strains were
      Western CagA-positive. The phylogenetic tree based on the deduced amino acid
      sequence of CagA indicated that the Philippine strains were classified into the
      two major groups of CagA protein: the Western and the East Asian group. These
      findings suggest that the modern Western influence may have resulted in more
      Western type H. pylori strains in the Philippines. Therefore, H. pylori-infected
      Filipinos can be considered to be at a low risk of developing gastric cancer.

PMID- 20670276
TI  - Diterpene production in Mycobacterium tuberculosis.
AB  - Diterpenes are a structurally diverse class of molecules common in plants,
      although they are very rarely found in bacteria. We report the identification in
      Mycobacterium tuberculosis (Mtb) of three diterpenes proposed to promote
      phagolysosome maturation arrest. MS analysis reveals that these diterpenes are
      novel compounds not previously identified in other organisms. The diterpene with
      highest abundance in Mtb has a mass fragmentation pattern identical to
      edaxadiene, which is produced in vitro from geranylgeranyl diphosphate by the
      enzymes Rv3377c and Rv3378c. A second diterpene found in Mtb has a similar mass
      spectrum, and is always observed in the same proportion relative to edaxadiene,
      indicating that it is a side product of the Rv3378c reaction in vivo. We name
      this second diterpene olefin edaxadiene B. The least abundant of the three
      diterpenes in Mtb extracts is tuberculosinol, a dephosphorylated side-product of
      the edaxadiene pathway intermediate produced by Rv3377c. A frameshift in Rv3377c
      in Mtb completely eliminates diterpene production, whereas expression of Rv3377c
      and Rv3378c in the nonpathogenic M. smegmatis is sufficient to produce edaxadiene
      and edaxadiene B. These studies define the pathway of edaxadiene and edaxadiene B
      biosynthesis in vivo. Rv3377c and Rv3378c are unique to Mtb and M. bovis, making
      them candidates for selective therapeutics and diagnostics.

PMID- 20670278
TI  - Making sense of G-quadruplex and i-motif functions in oncogene promoters.
AB  - The presence and biological importance of DNA secondary structures in eukaryotic
      promoters are becoming increasingly recognized among chemists and biologists as
      bioinformatics in vitro and in vivo evidence for these structures in the c-Myc, c
      Kit, KRAS, PDGF-A, hTERT, Rb, RET and Hif-1alpha promoters accumulates.
      Nevertheless, the evidence remains largely circumstantial. This minireview
      differs from previous ones in that here we examine the diversity of G-quadruplex
      and i-motif structures in promoter elements and attempt to categorize the
      different types of arrangements in which they are found. For the c-Myc G
      quadruplex and Bcl-2 i-motif, we summarize recent biological and structural
      studies.

PMID- 20670279
TI  - Structure, location and interactions of G-quadruplexes.
AB  - Four-stranded G-rich DNA structures called G-quadruplexes have been the subject
      of increasing interest recently. Experimental and computational techniques have
      been used to implicate them in important biological processes such as
      transcription and translation. In this minireview, I discuss how they form, what
      structures they adopt and with what stability. I then discuss the computational
      approaches used to predict them on a genomic scale and how the information
      derived can be combined with experiments to understand their biological
      functions. Other minireviews in this series deal with G-quadruplex nucleic acids
      and human disease [Wu Y & Brosh RM Jr (2010) FEBS J] and making sense of G
      quadruplex and i-motif function in oncogene promoters [Brooks TA et al. (2010)
      FEBS J].

PMID- 20670277
TI  - G-quadruplex nucleic acids and human disease.
AB  - Alternate DNA structures that deviate from B-form double-stranded DNA such as G
      quadruplex (G4) DNA can be formed by sequences that are widely distributed
      throughout the human genome. G-quadruplex secondary structures, formed by the
      stacking of planar quartets composed of four guanines that interact by Hoogsteen
      hydrogen bonding, can affect cellular DNA replication and transcription, and
      influence genomic stability. The unique metabolism of G-rich chromosomal regions
      that potentially form quadruplexes may influence a number of biological processes
      including immunoglobulin gene rearrangements, promoter activation and telomere
      maintenance. A number of human diseases are characterized by telomere defects,
      and it is proposed that G-quadruplex structures which form at telomere ends play
      an important role in telomere stability. Evidence from cellular studies and model
      organisms suggests that diseases with known defects in G4 DNA helicases are
      likely to be perturbed in telomere maintenance and cellular DNA replication. In
      this minireview, we discuss the connections of G-quadruplex nucleic acids to
      human genetic diseases and cancer based on the recent literature.

PMID- 20670280
TI  - DNA G-quadruplex: structure, function and human disease.

PMID- 20670283
TI  - Cerebral sinus venous thrombosis in children: an urgent need for multicentre
      trials.

PMID- 20670282
TI  - M-tropic HIV envelope protein gp120 exhibits a different neuropathological
      profile than T-tropic gp120 in rat striatum.
AB  - Most early human immunodeficiency virus type 1 (HIV-1) strains are macrophage (M)
      tropic HIV variants and use the chemokine receptor CCR5 for infection. Neuronal
      loss and dementia are less severe among individuals infected with M-tropic
      strains. However, after several years, the T-cell (T)-tropic HIV strain, which
      uses the CXCR4 variant, can emerge in conjunction with brain abnormalities,
      suggesting strain-specific differences in neuropathogenicity. The molecular and
      cellular mechanisms of such diversity remain under investigation. We have
      previously demonstrated that HIV envelope protein gp120IIIB, which binds to
      CXCR4, causes neuronal apoptosis in rodents. Thus, we have used a similar
      experimental model to examine the neurotoxic effects of M-tropic gp120BaL.
      gp120BaL was microinjected in the rat striatum and neuronal apoptosis was
      examined in the striatum, as well as in anatomically connected areas, such as the
      somatosensory cortex and the substantia nigra. gp120BaL promoted neuronal
      apoptosis and tissue loss that were confined to the striatum. Apoptosis was
      associated with microglial activation and increased levels of interleukin-1beta.
      Intriguingly, gp120BaL increased brain-derived neurotrophic factor in the
      striatum. Overall, our data show that gp120BaL demonstrates a different
      neuropathological profile than gp120IIIB. A better understanding of the
      pathogenic mechanisms mediating HIV neurotoxicity is vital for developing
      effective neuroprotective therapies against AIDS-associated dementia complex.

PMID- 20670284
TI  - Reference values for anaerobic performance and agility in ambulatory children and
      adolescents with cerebral palsy.
AB  - AIM: the aim of this study was to provide reference values of anaerobic
      performance and agility in a group of children and adolescents with spastic
      cerebral palsy (CP). METHOD: a total of 300 children (184 males, 116 females)
      with spastic CP were recruited from 26 rehabilitation centres in six different
      countries. Of these, 215 were classified at GMFCS level I (mean age 11y 2mo, SD
      3y, range 6-18y) and 85 were classified at GMFCS level II (mean age 11y; SD 3y
      1mo, range 6-18y). The children performed the Muscle Power Sprint Test (MPST) and
      the 10*5m sprint test in a standardized manner. To establish reference values,
      reference curves were created using generalized additive models for location,
      scale, and shape. RESULTS: height-related reference curves were created based on
      performance on the two tests. INTERPRETATION: this study provides height-related
      reference values for anaerobic performance and agility for children and
      adolescents with CP classified at GMFCS levels I and II. These curves are
      clinically relevant and provide a user-friendly method in the interpretation of
      anaerobic performance and agility for children with spastic CP.

PMID- 20670286
TI  - Diagnosing infections--current and anticipated technologies for point-of-care
      diagnostics and home-based testing.
AB  - In recent years, we have witnessed many transitions in healthcare systems around
      the globe. For example, population expansion and ageing, and the human
      immunodeficiency virus (HIV)-AIDS epidemics, have exerted pressure to
      decentralize the practice of healthcare outside of traditional settings to bring
      care to those in need. Upstream of patient management, diagnosis is aimed at
      adequately orienting medical decisions, and considerable efforts have been made
      to make this process faster and more efficient. However, there are several
      diseases and medical conditions that may/will benefit from technologies and tests
      that can be performed closer to the patient, at the point of care or even in the
      home. In this review, and in light of the paradox that technology and assay
      developers and healthcare officials must take into consideration for advancing
      human health in developed and developing countries, we present an overview of
      rapid diagnosis of infectious diseases at the point of care and of technologies
      that may contribute to enhancement of the worldwide point-of-care testing market.

PMID- 20670287
TI  - Routine use of point-of-care tests: usefulness and application in clinical
      microbiology.
AB  - Point-of-care (POC) tests offer potentially substantial benefits for the
      management of infectious diseases, mainly by shortening the time to result and by
      making the test available at the bedside or at remote care centres. Commercial
      POC tests are already widely available for the diagnosis of bacterial and viral
      infections and for parasitic diseases, including malaria. Infectious diseases
      specialists and clinical microbiologists should be aware of the indications and
      limitations of each rapid test, so that they can use them appropriately and
      correctly interpret their results. The clinical applications and performance of
      the most relevant and commonly used POC tests are reviewed. Some of these tests
      exhibit insufficient sensitivity, and should therefore be coupled to confirmatory
      tests when the results are negative (e.g. Streptococcus pyogenes rapid antigen
      detection test), whereas the results of others need to be confirmed when positive
      (e.g. malaria). New molecular-based tests exhibit better sensitivity and
      specificity than former immunochromatographic assays (e.g. Streptococcus
      agalactiae detection). In the coming years, further evolution of POC tests may
      lead to new diagnostic approaches, such as panel testing, targeting not just a
      single pathogen, but all possible agents suspected in a specific clinical
      setting. To reach this goal, the development of serology-based and/or molecular
      based microarrays/multiplexed tests will be needed. The availability of modern
      technology and new microfluidic devices will provide clinical microbiologists
      with the opportunity to be back at the bedside, proposing a large variety of POC
      tests that will allow quicker diagnosis and improved patient care.

PMID- 20670288
TI  - Point-of-care tests for diagnosing infections in the developing world.
AB  - Infectious diseases continue to cause an enormous burden of death and disability
      in developing countries. Increasing access to appropriate treatment for
      infectious diseases could have a major impact on disease burden. Some common
      infections can be managed syndromically without the need for diagnostic tests,
      but this is not appropriate for many infectious diseases, in which a positive
      diagnostic test is needed before treatment can be given. Since many people in
      developing countries do not have access to laboratory services, diagnosis depends
      on the availability of point of care (POC) tests. Historically there has been
      little investment in POC tests for diseases that are common in developing
      countries, but that is now changing. Lack of regulation of diagnostic tests in
      many countries has resulted in the widespread use of sub-standard POC tests,
      especially for malaria, making it difficult for manufacturers of reliable POC
      tests to compete. In recent years increased investment, technological advances,
      and greater awareness about the importance of reliable diagnostic tests has
      resulted in rapid progress. Rapid, reliable and affordable POC tests, requiring
      no equipment and minimal training, are now available for HIV infection, syphilis
      and malaria, but POC tests for other infections are urgently needed. Many
      countries do not have established criteria for licensing and introducing new
      diagnostic tests, and many clinicians in developing countries have become
      disillusioned with diagnostic tests and prefer to rely on clinical judgment.
      Continuing advocacy and training in the use of POC tests are needed, and systems
      for quality control of POC tests need to be developed if they are to achieve
      their maximum potential.

PMID- 20670289
TI  - Economic evaluation of point-of-care diagnostic technologies for infectious
      diseases.
AB  - We review the growing number of economic evaluations of individual point-of-care
      (POC) tests for diagnosis of infectious diseases in resource-limited settings
      that use either cohort studies or mathematical models. We focus on studies that
      evaluate POC diagnostic tests for the control of human immunodeficiency virus
      (HIV) and malaria, tools that are central to the WHO prevention guidelines for
      infectious diseases in developing countries. Although rapid diagnostic tests for
      HIV and malaria seem to be cost-effective in these standard analyses, these do
      not take into account the reduction in patients' waiting time and the number of
      clinic visits required to receive results, or future benefits from the reduction
      in antimalarial drug pressure. Those additional cost reductions would be
      considerably greater with POC rapid tests, and the cost-effectiveness of POC
      tests would therefore be improved. Findings from cost-effectiveness analyses
      suggest that, despite the relatively small additional cost incurred, decision
      makers should strongly consider using POC tests throughout or during parts of HIV
      and malaria epidemics, where this is feasible in terms of local human resources
      and logistical conditions.

PMID- 20670290
TI  - Emergence of extended-spectrum beta-lactamase-producing Escherichia coli and
      Klebsiella pneumoniae during the years 2000 and 2004 in Helsinki, Finland.
AB  - The molecular epidemiology of 33 Escherichia coli and 81 Klebsiella pneumoniae
      extended-spectrum beta-lactamase-producing healthcare-associated and community
      acquired isolates collected in the Helsinki district during 2000-2004 was
      investigated. Clonality studies, antimicrobial susceptibility and genotyping of
      the isolates were performed. Newly emerging CTX-M-producing E. coli and bla(SHV
      12)-producing K. pneumoniae isolates were detected. Clonal clusters of both
      species persisted throughout the study period.

PMID- 20670291
TI  - Transmission of cytomegalovirus via breast milk to the prematurely born infant: a
      systematic review.
AB  - To analyse current data on transmission of human cytomegalovirus (HCMV) via
      breast milk with subsequent symptomatic HCMV infection of the preterm infant and
      to report on long-term follow-up, a systematic literature review was performed
      using EMBASE, MEDLINE and CINAHL (January 1966 to December 2008) Studies were
      included for analysis if congenital HCMV infection was excluded and transmission
      via breast milk was either confirmed or strongly suspected. Twenty-six studies
      were included for analysis. Maternal HCMV-IgG-positivity was reported to be in
      the range 51.6-100% (median 81.6%), HCMV-IgG detection in breast milk in the
      range 67-97.2% (median 80%) and HCMV-positivity of the infants in the range 5.7
      58.6%. Symptomatic HCMV disease occurred in 0-34.5% (median 3.7%) and severe
      sepsis-like syndrome in 0-13.8% (median 0.7%). Data on long-term outcome of
      preterm infants with symptomatic HCMV infection revealed a low risk for mild
      neurological and cognitive sequelae, without hearing impairment. Recommendations
      for high-risk preterm infants diverged markedly. The current data report low
      rates of symptomatic disease after transmission of HCMV via breast milk to the
      preterm infant without evidence of certain long-term sequelae. The results of our
      review do not support a general approach, either by avoidance or pasteurization
      of breast milk, in high-risk preterm infants.

PMID- 20670292
TI  - Cellular immune responses to recurring influenza strains have limited boosting
      ability and limited cross-reactivity to other strains.
AB  - Influenza vaccine provides protection against infection with matched strains, and
      this protection correlates with serum antibody titres. In addition to antibodies,
      influenza-specific CD8+ T-lymphocyte responses are important in decreasing
      disease severity and facilitating viral clearance. Because this response is
      directed at internal, relatively conserved antigens, it affords some cross
      protection within a given subtype of influenza virus. With the possibility of a
      broader A(H1N1) Mexico outbreak in the fall of 2009, it appeared worthwhile
      studying the degree of cellular immune response-mediated cross-reactivity among
      influenza virus isolates. The composition of the 2006-2007 influenza vaccine
      included the A/New Caledonia/20/1999 strain (comprising a virus that has been
      circulating, and was included in vaccine preparations, for 6-7 years) and two
      strains not previously included (Wisconsin and Malaysia). This combination
      afforded us the opportunity to determine the degree of cross-reactive cellular
      immunity after exposure to new viral strains. We analysed the antibody responses
      and the phenotype and function of the T cell response to vaccine components. The
      results obtained show that antibody responses to A/New-Caledonia were already
      high and vaccination did not increase antibody or cytotoxic T lymphocyte
      responses. These data suggest that repeated exposure to the same influenza stain
      results in limited boosting of humoral and cellular immune responses.

PMID- 20670293
TI  - A multicentre, open-label, randomized comparative study of tigecycline versus
      ceftriaxone sodium plus metronidazole for the treatment of hospitalized subjects
      with complicated intra-abdominal infections.
AB  - Tigecycline (TGC) has demonstrated clinical efficacy and safety, in comparison
      with imipenem/cilastatin in phase 3 clinical trials, for complicated intra
      abdominal infection (cIAI). The present study comprised a multicentre, open
      label, randomized study of TGC vs. ceftriaxone plus metronidazole (CTX/MET) for
      the treatment of patients with cIAI. Eligible subjects were randomized (1:1) to
      receive either an initial dose of TGC (100 mg) followed by 50 mg every 12 h or
      CTX (2 g once daily) plus MET (1-2 g daily), for 4-14 days. The primary endpoint
      was the clinical response in the clinically evaluable (CE) population at the test
      of cure (TOC) assessment. Of 473 randomized subjects, 376 were CE. Among these,
      clinical cure rates were 70.4% (133/189) with TGC vs. 74.3% (139/187) with
      CTX/MET (95% CI -13.1 to 5.1; p 0.009 for non-inferiority). Clinical cure rates
      for subjects with Acute Physiological and Chronic Health Evaluation II scores >
      or =10 were 56.8% (21/37) with TGC vs. 58.3% (21/36) with CTX/MET. The
      microbiologic response was similar between the two treatment arms, with
      microbiological eradication at TOC achieved in 68.1% (94/138) of TGC-treated
      subjects and 71.5% (98/137) of CTX/MET-treated subjects. (The most frequently
      reported adverse events (AEs) for both treatment arms were nausea (TGC, 38.6% vs
      CTX/MET, 27.7%) and vomiting (TGC, 23.3% vs CTX/MET, 17.7%). Overall
      discontinuation rates as a result of an AE were 8.9% and 4.8% in TGC- and
      comparator-treated subjects, respectively. The results obtained in the present
      study demonstrate that TGC monotherapy is non-inferior to a combination regimen
      of CTX/MET with respect to treating subjects with cIAI.

PMID- 20670294
TI  - Innate immune encounters of the (Type) 4th kind: Brucella.
AB  - In humans, pathogenic Brucella species cause a febrile illness known as
      brucellosis. A key pathogenic trait of this group of organisms is their ability
      to survive in immune cells and persist in tissues of the reticuloendothelial
      system, a process that requires the function of a Type IV secretion system. In
      contrast to other well-studied Gram-negative bacteria, Brucella spp. do not cause
      inflammation at the site of invasion, but have a latency period of 2-4 weeks
      before the onset of symptoms. This review discusses several mechanisms that allow
      Brucella spp. both to evade detection by pattern recognition receptors of the
      innate immune system and suppress their signalling. In contrast to these stealth
      features, the VirB Type IV secretion system, which mediates survival within
      phagocytic cells, stimulates innate immune responses in vivo. The responses
      stimulated by this virulence factor are sufficient to check bacterial growth, but
      not to elicit sterilizing immunity. The result is a stand-off between host and
      pathogen that results in persistent infection.

PMID- 20670296
TI  - Acetyl salicylic acid (aspirin) improves synthesis of maspin and lowers incidence
      of metastasis in breast cancer patients [corrected].
AB  - Maspin, a 42 kDa protein produced in normal breast cells, has been shown to
      inhibit the invasion and metastasis of breast cancer in an animal model.
      Ingestion of acetylsalicylic acid (aspirin) by breast cancer patients has been
      reported to restore the systemic synthesis of maspin through the stimulation of
      systemic nitric oxide production. Studies were carried out to determine the
      effect of aspirin on the incidence of breast cancer metastasis, which is reported
      to occur in 50% of patients who have previously received chemotherapy, radiation,
      and/or surgery. Thirty-five female patients (aged 41-65 years) with breast cancer
      who had previously received these therapies took one 75 mg/70 kg body weight
      enteric-coated aspirin tablet every 24 h, after an adequate meal, for 3 years.
      Their plasma nitric oxide and maspin levels were measured. The occurrence of
      metastasis was ascertained monthly by a qualified oncologist, and confirmed, if
      necessary, by biopsy. Daily ingestion of aspirin by participants resulted in an
      increase in maspin levels from 0.95 +/- 0.04 to 4.63 +/- 0.05 nM after 24 h.
      These levels were maintained for 3 years. These studies suggest that daily
      ingestion of aspirin might significantly reduce the incidence of breast cancer
      metastasis in patients who have previously received anticancer therapies.

PMID- 20670295
TI  - Type IV secretion in the obligatory intracellular bacterium Anaplasma
      phagocytophilum.
AB  - Anaplasma phagocytophilum is an obligatory intracellular bacterium that infects
      neutrophils, the primary host defence cells. Consequent effects of infection on
      host cells result in a potentially fatal systemic disease called human
      granulocytic anaplasmosis. Despite ongoing reductive genome evolution and
      deletion of most genes for intermediary metabolism and amino acid biosynthesis,
      Anaplasma has also experienced expansion of genes encoding several components of
      the type IV secretion (T4S) apparatus. Two A. phagocytophilum T4S effector
      molecules are currently known; Anaplasma translocated substrate 1 (Ats-1) and
      ankyrin repeat domain-containing protein A (AnkA) have C-terminal positively
      charged amino acid residues that are recognized by the T4S coupling protein,
      VirD4. AnkA and Ats-1 contain eukaryotic protein motifs and are uniquely evolved
      in the family Anaplasmataceae; Ats-1 contains a mitochondria-targeting signal.
      They are abundantly produced and secreted into the host cytoplasm, are not toxic
      to host cells, and manipulate host cell processes to aid in the infection
      process. At the cellular level, the two effectors have distinct subcellular
      localization and signalling in host cells. Thus in this obligatory intracellular
      pathogen, the T4S system has evolved as a host-subversive survival factor.

PMID- 20670297
TI  - Nobiletin, a citrus polymethoxyflavonoid, suppresses multiple angiogenesis
      related endothelial cell functions and angiogenesis in vivo.
AB  - Nobiletin is a citrus polymethoxyflavonoid that suppresses tumor growth and
      metastasis, both of which depend on angiogenesis. We recently identified
      nobiletin as a cell differentiation modulator. Because cell differentiation is a
      critical event in angiogenesis, it might be possible that nobiletin could exhibit
      antiangiogenic activity, resulting in suppression of these tumor malignant
      properties. To verify this possibility, we examined the antiangiogenic effects of
      nobiletin in vitro and in vivo. Nobiletin had concentration-dependent inhibitory
      effects on multiple functions of angiogenesis-related endothelial cells (EC); it
      suppressed the proliferation, migration and tube formation on matrigel of human
      umbilical vein EC (HUVEC) stimulated with endothelial cell growth supplement
      (ECGS), a mixture of acidic and basic fibroblast growth factors (FGFs). Gelatin
      zymography and northern blotting revealed that nobiletin suppressed pro-matrix
      metalloproteinase-2 (proMMP-2) production and MMP-2 mRNA expression in ECGS
      stimulated HUVEC. Nobiletin also downregulated cell-associated plasminogen
      activator (PA) activity and urokinase-type PA mRNA expression. Furthermore,
      nobiletin inhibited angiogenic differentiation induced by vascular endothelial
      growth factor and FGF, an in vitro angiogenesis model. This inhibition was
      accompanied by downregulation of angiogenesis-related signaling molecules, such
      as extracellular signal-regulated kinase 1/2 and c-Jun N-terminal kinase, and
      transcriptional factors (c-Jun and signal transducer and activator of
      transcription 3), and activation of the caspase pathway. In a chick embryo
      chorioallantoic membrane assay, nobiletin showed an antiangiogenic activity, the
      ID(50) value being 10MUg (24.9nmol) per egg. These results indicate that
      nobiletin is a novel antiangiogenic compound that exhibits its activity through
      combined inhibition of multiple angiogenic EC functions.

PMID- 20670298
TI  - Multiple primary melanoma: the impact of atypical naevi  and follow up.
AB  - BACKGROUND: Patients with melanoma are especially encouraged to have regular
      follow- up visits with their dermatologist and to perform total-body skin
      examination on a routine basis to identify new pigmented lesions or detect
      significant changes in existing naevi. OBJECTIVES: To identify main risk factors
      (sex, age, number of common and atypical naevi, family history, phototype)
      associated with multiple primary melanomas (MPM) and to investigate the
      association between regular follow up and tumour thickness of a second primary
      melanoma. METHODS: We performed a retrospective analysis of patients with MPM in
      order to evaluate risk factors for developing a second primary melanoma. Medical
      records of patients with melanoma who developed a second primary melanoma were
      selected from a database of all patients with histopathologically confirmed
      melanoma treated at the dermatology clinic of the University of Florence, Italy,
      from 2000 to 2004. Medical data culled from the patient records were as follows:
      medical history, number of typical naevi, presence of atypical naevi, Breslow
      thickness, Clark level and histotype of the melanomas, site of the melanomas and
      patient adherence to 6-month follow-up examinations. RESULTS: The presence of
      atypical naevi was associated with a higher risk of developing MPM (adjusted odds
      ratio 3.28, 95% confidence interval 1.35-7.44). Moreover, in the subjects who did
      not attend follow up, we noted that the thickness of the second melanoma was
      significantly higher, with a mean thickness of 1.22 mm, in comparison with
      patients with a careful adherence to follow up in whom the mean thickness was
      0.36 mm (P = 0.0189). CONCLUSIONS: For the first time, the validity of this
      clinical approach has been supported by real comparison of thickness levels of
      second melanoma in patients with or without periodical follow up. Results
      obtained from this analysis show that follow up is an effective method for early
      detection of melanoma.

PMID- 20670299
TI  - Pruritic reddish-brown papules and plaques as initial skin lesions in a case of
      antilaminin gamma1 pemphigoid without psoriasis.

PMID- 20670300
TI  - Urinary aquaporin-2 is elevated in infant atopic dermatitis.

PMID- 20670301
TI  - Fetoscopic laser coagulation for severe twin-to-twin transfusion syndrome:
      factors influencing perinatal outcome, learning curve of the procedure and
      lessons for new centres.
AB  - OBJECTIVE:   To evaluate the effects of operator experience on perinatal outcome
      in a single centre. DESIGN:   Prospective consecutive cohort study. SETTING:  
      Regional tertiary referral Fetal Medicine Centre in the UK. POPULATION:  
      Pregnant women with monochorionic twin pregnancies complicated by severe twin-to
      twin transfusion syndrome (TTTS) (at <=26 completed weeks of gestatiuon) treated
      by fetoscopic laser coagulation (FLC) between October 2004 and November 2009.
      METHODS:   Pregnancy characteristics and outcomes were collected. Logistic
      regression analysis was employed to determine the effect of a priori defined
      variables on outcome. MAIN OUTCOME MEASURE:   Perinatal survival (survival to 28
      days or beyond) for one or more twins. RESULTS:   There were 164 consecutive sets
      of monochorionic twins. The median gestational age (GA) at FLC was 20.4 weeks
      (interquartile range 18-22.1 weeks), the median interval from FLC to delivery was
      88.5 days (interquartile range 53-101 days) and the median GA at delivery was
      33.2 weeks (interquartile range 29.7-34.9 weeks). The overall survival was 62%;
      perinatal survival of one or more twins was 85%. These outcomes improved after
      about 61 procedures were performed, and after about 3.4 years of experience.
      Univariate logistic regression analysis indicated that Quintero stage-IV disease
      decreased (OR 0.26; 95% CI 0.10-0.69) and prolongation of GA at delivery
      increased the survival of the twins (OR 1.34; 95% CI 1.12-1.60) (P < 0.01).
      Increasing experience of the procedure by operator led to a significant increase
      in perinatal survival (P < 0.01; OR 4.59; 95% CI 1.84-11.44). Multivariate
      logistic regression analysis indicated that only GA at delivery increased
      survival overall (OR 1.34; 95% CI 1.12-1.60; P = 0.01). CONCLUSIONS:   These data
      indicate that both relatively large numbers treated and experience with FLC
      minimises any adverse outcome in monochorionic pregnancies with severe TTTS.

PMID- 20670302
TI  - The role of a maternity waiting area (MWA) in reducing maternal mortality and
      stillbirths in high-risk women in rural Ethiopia.
AB  - OBJECTIVE: To describe maternal mortality and stillbirth rates among women
      admitted via a maternity waiting area (MWA) and women admitted directly to the
      same hospital (non-MWA) over a 22-year period. DESIGN:  Retrospective cohort
      study. SETTING:   Hospital in rural Ethiopia, which provided comprehensive
      emergency obstetric care and has an established MWA. POPULATION:   All women
      admitted for delivery between 1987 and 2008. METHODS:   Data on maternal deaths,
      stillbirths, caesarean section and uterine rupture were abstracted from routine
      hospital records. Sociodemographic characteristics, antenatal care and other data
      were collected for 2008 only. Rates and 95% confidence intervals were calculated
      for maternal mortality and stillbirth. MAIN OUTCOME MEASURES: Maternal mortality
      and stillbirth. RESULTS:  There were 24, 148 deliveries over the study period,
      6805 admitted via MWA and 17, 343 admitted directly. Maternal mortality was 89.9
      per 100, 000 live births (95% CI, 41.1-195.2) for MWA women and 1333.1 per 100,
      000 live births (95% CI, 1156.2-1536.7) for non-MWA women; stillbirth rates were
      17.6 per 1000 births (95% CI, 14.8-21.0) and 191.2 per 1000 births (95% CI, 185.4
      197.1), respectively; 38.5% of MWA women were delivered by caesarean section
      compared with 20.3% of non-MWA women, and none had uterine rupture, compared with
      5.8% in the non-MWA group. For the 1714 women admitted in 2008, relatively small
      differences in sociodemographic characteristics, distance and antenatal care
      uptake were found between groups. CONCLUSIONS: Maternal mortality and stillbirth
      rates were substantially lower in women admitted via MWA. It is likely that at
      least part of this difference is accounted for by the timely and appropriate
      obstetric management of women using this facility.

PMID- 20670303
TI  - Robust prediction of t-year survival with data from multiple studies.
AB  - Recently meta-analysis has been widely utilized to combine information across
      multiple studies to evaluate a common effect. Integrating data from similar
      studies is particularly useful in genomic studies where the individual study
      sample sizes are not large relative to the number of parameters of interest. In
      this article, we are interested in developing robust prognostic rules for the
      prediction of t-year survival based on multiple studies. We propose to construct
      a composite score for prediction by fitting a stratified semiparametric
      transformation model that allows the studies to have related but not identical
      outcomes. To evaluate the accuracy of the resulting score, we provide point and
      interval estimators for the commonly used accuracy measures including the time
      specific receiver operating characteristic curves, and positive and negative
      predictive values. We apply the proposed procedures to develop prognostic rules
      for the 5-year survival of breast cancer patients based on five breast cancer
      genomic studies.

PMID- 20670304
TI  - Opposing responses of apoptosis and autophagy to moderate compression in skeletal
      muscle.
AB  - AIM: The molecular mechanism that contributes to the pathogenesis of deep
      pressure ulcer remains to be elucidated. This study tested the hypotheses that:
      (1) apoptosis and autophagy are activated in compression-induced muscle pathology
      and (2) apoptotic and autophagic changes precede pathohistological changes in
      skeletal muscle in response to prolonged moderate compression. METHODS:   Adult
      Sprague-Dawley rats were subjected to an experimental model of pressure-induced
      deep tissue injury. Static pressure of 100 mmHg was applied to an area of 1.5
      cm(2) over the mid-tibialis region of right limb of rats for one single session
      of 6-h compression (1D) or two sessions of 6-h compression over two consecutive
      days with rats sacrificed one day (2D) or immediately after (2D-IM) the
      compression. The left uncompressed limb served as the intra-animal control.
      Muscle tissues underneath compression region were collected for analysis.
      RESULTS: Our histological analysis indicated that pathohistological
      characteristics including rounding contour of myofibres and massive nuclei
      accumulation were apparently demonstrated in muscles of 2D and 2D-IM. In
      contrast, these pathohistological changes were generally not found in muscle
      following 1D. Apoptotic DNA fragmentation, terminal dUTP nick-end labelling index
      and caspase-3 protease activity were significantly elevated in compressed muscles
      of all groups. Caspase-9 enzymatic activity was found to be significantly
      increased in compressed muscles of 2D and 2D-IM whereas increase in caspase-8
      activity was exclusively found in compressed muscle of 1D. According to our
      immunoblot analysis, FoxO3 was significantly reduced in compressed muscles of all
      groups whereas Beclin-1 was decreased only in 2D. LC3-I was significantly reduced
      in compressed muscles of all groups while LC3-II was decreased in 2D and 1D. No
      significant differences were found in the protein abundance of Akt and phospho
      Akt in muscles among all groups. CONCLUSION: These data demonstrate the opposing
      responses of apoptosis and autophagy to moderate compression in muscle. Moreover,
      our findings suggest that cellular changes in apoptosis and autophagy have
      already taken place in the very early stage in which apparent histopathology has
      yet to develop in the process of compression-induced muscle pathology.

PMID- 20670305
TI  - Early fish introduction is associated with less eczema, but not sensitization, in
      infants.
AB  - OBJECTIVE: To investigate if the development of allergic diseases during the
      child's first 18 months of life is influenced by the time at which different food
      items were introduced into the child's diet. METHOD: A birth cohort of 184
      children was followed to 18 months of age. Diaries were used to document feeding
      practices, and parental interviews were performed at 6 and 12 months of age,
      probing for symptoms suggesting allergic disease, general health-related issues
      and food introduction regimes. Symptoms promoted prompt clinical examination, and
      all children were examined clinically, and tested for sensitization to common
      airborne and food allergens at 18 months of age. RESULTS: The earlier the fish
      was introduced into the child's diet the lower was the frequency of eczema. This
      association remained after control for confounding factors. The timing of fish
      introduction and asthma development showed a similar pattern, but did not reach
      statistical significance. Sensitization was not influenced by the timing of fish
      introduction. Other food items or feeding practices did not seem to influence
      allergy development. CONCLUSION:   Early introduction of fish into the child's
      diet was associated with less eczema development, and a tendency to less asthma.
      Sensitization was not associated with the timing of fish introduction.

PMID- 20670306
TI  - Predictive value of the 1-min Apgar score for survival at 23-26 weeks gestational
      age.
AB  - AIM:   Is a 1-min Apgar score <=1 predictive of mortality in resuscitated
      extremely premature infants? METHODS:  A retrospective case-control review of all
      infants with gestational ages < 27 weeks over a 5-year period. All values as
      median [75% CI]. RESULTS:  Of 237 infants, 29 had 1-min Apgar scores <=1 (Group
      1) and 208 had scores >1 (Group 2). Despite earlier and more frequent intubation
      (2 min [2.3; 6.7] vs. 5 min [7.5; 10] and 93% vs. 77%, p = 0.04), mortality was
      higher in Group 1 (62% vs. 17%; p < 0.0001). Age at death did not differ (Group
      1: 3.5days [1; 30] vs. Group 2: 6 days [6; 44]). Birth weight and sex were the
      best predictors of survival. With a 1-min Apgar score of 1, a male infant at 23
      weeks and 500g had a mortality rate of 92%. CONCLUSION:   Despite successful
      resuscitation, infants between 23 and 26 weeks have a very poor prognosis for
      survival when presenting with bradycardia, cyanosis and no respiratory efforts (1
      min Apgar = 1) at birth. According to our data, initiating active treatment for
      an infant at 23 weeks with bradycardia and apnoea is almost always unsuccessful,
      whereas by 26 weeks gestation, the chance of survival is higher than the
      probability of death.

PMID- 20670307
TI  - Autism: screening toddlers with CHAT in a child health care programme did not
      improve early identification.

PMID- 20670308
TI  - Environmental cooling of the newborn pig brain during whole-body cooling.
AB  - AIM: Therapeutic hypothermia after perinatal asphyxia decreases brain injury in
      newborns, whereas hyperthermia worsens the brain injury. We examined how
      different clinical practices influence regional brain temperatures during
      hypothermia. METHODS: Six newborn pigs, which have comparable physiology and
      brain maturation to human term infants, were maintained at hypothermia (33.5
      degrees C) or normothermia with a servo-controlled whole-body cooling device that
      is in clinical use. Pigs were anesthetized and fully instrumented for
      cardiovascular and temperature (rectal and regional brain) monitoring. Changes in
      brain temperatures were measured during four different paradigms to mimic
      different clinical practices. RESULTS: Inserting an insulating pillow between the
      head and the heated surface reduced cortex temperature by 1 or 2 degrees C during
      normothermia (core temperature T(core) 37 degrees C) or hypothermia, T(core) 33.5
      degrees C. Reducing ambient temperature from 28 degrees C to 23 degrees C reduced
      cortex temperature by 3.9 +/- 1.9 degrees C. Without a hat and overhead heater at
      normothermia, cortex and deep brain temperatures were reduced by 1.2 +/- 0.8 and
      0.7 +/- 0.7 degrees C, respectively. Direct overhead heating abolished the normal
      cortex to deep brain temperature gradient that was maintained if using a head
      shield. CONCLUSION: Brain temperature may differ from core temperature during
      therapeutic hypothermia influenced by different clinical practices.

PMID- 20670309
TI  - Feeding of very low birth weight infants born to HCMV-seropositive mothers in
      Germany, Austria and Switzerland.
AB  - AIM:   To evaluate the enteral feeding practice of preterm infants <32 weeks (W)
      gestational age (GA) or <1500 g birth weight (BW) from human cytomegalovirus
      (HCMV)-seropositive mothers in Germany, Austria and Switzerland. METHODS:   This
      prospective cross-sectional study included all neonatal units (NU) admitting
      preterm infants <32W or <1500g BW in Germany, Austria and Switzerland. In June
      and July 2009, an anonymized questionnaire was sent via e-mail, asking whether
      mothers of the above patients were screened for HCMV, and about the enteral
      feeding protocol for preterm infants <32W GA or <1500g BW from HCMV-seropositive
      mothers. RESULTS:  During the study period, 58.6% of the questionnaires (123/210)
      from Germany, 50% (13/26) from Austria and 50% (6/12) from Switzerland were
      returned, yielding a total of 6232 preterm infants for analysis. Formula was
      given to the mentioned preterm infants in 28.5% (35/123) of the German NUs but
      not in Austria or Switzerland. Untreated breast milk was given in 66.6% (4/6) of
      the Swiss, 14.6% (18/123) of the German and no Austrian NU. Long-term pasteurized
      breast milk was given in 32.5% (40/123) of the German and 38.5% (5/13) of the
      Austrian NUs, but not in Switzerland. Short-term pasteurized breast milk was
      given only in 5.7% (7/123) of German NUs. Freeze-thawed breast milk was given in
      Germany (4.9%; 6/123), Austria (61.5%; 8/13) and Switzerland (16.7%; 1/6).
      CONCLUSION:   Preterm infants <32W GA or <1500g BW born to HCMV-seropositive
      mothers are fed according to different regimes in German-speaking countries.
      About 28.5% of the German VLBW-infants receive formula, which is not recommended.

PMID- 20670310
TI  - Improvement of developmental outcome between 24 and 36 months corrected age in
      very preterm infants.
AB  - AIM:  To study early developmental course in preschool-aged very preterm infants
      and its association with perinatal risk factors and test-taking behaviour.
      METHODS:   Children born <30 weeks gestation and/or <1000g in the Academic
      Medical Center of Amsterdam were assessed at 24 and 36 months corrected age with
      the Dutch Bayley Scales of Infant Development-II (BSID-II-NL) and neurological
      examination. Linear regression analyses for developmental change were performed
      with perinatal risk factors. RESULTS:   One hundred and forty-six children, mean
      GA 28 weeks and mean birth weight 1043 g, participated. Mental and psychomotor
      scores improved significantly with 6 and 7 points, respectively, from 24 to 36
      months (p < 0.01). Mild to severe problems on at least one domain occurred less
      often at 36 (32%) compared to 24 months (63%) (p < 0.01), using corrected scores.
      Mental improvement was associated with being born very small for gestational age
      or <28 weeks; psychomotor improvement was associated with not being treated with
      indomethacin. Difficult test behaviour occurred mostly at 24 months and was
      associated with non-optimal development at 36 months. CONCLUSION:   Improved
      developmental outcome and test behaviour were found at 36 compared to 24 months
      in a cohort of very preterm children. Long-term outcome studies and retesting of
      behaviourally difficult children are recommended.

PMID- 20670311
TI  - Aerobic fitness in prepubertal children according to level of body fat.
AB  - AIM: The purpose of this study was to investigate the relationship between
      maximum oxygen uptake (VO(2PEAK) ) and body fat in young children on a population
      based level. METHODS: Participants were 586 children (311 boys and 275 girls)
      aged 6.8+/-0.4 years, recruited from a population-based cohort. VO(2PEAK) was
      measured by indirect calorimetry during a maximal exercise test. Percent body fat
      (BF%) was estimated from skinfold measurements. RESULTS:   Significant
      relationships existed between BF% and absolute values of VO(2PEAK) (mL/min),
      VO(2PEAK) scaled by body weight (mL/min/kg) and VO(2PEAK) by allometric scaling
      (mL/min/kg(0.71) ), whereas no relationships were detected for VO(2PEAK) scaled
      to fat-free mass (FFM) (mL/min/FFM). Person correlation coefficients for boys
      were 0.26, -0.38, -0.19 and -0.01 NS and for girls 0.33, -0.42, -0.21 and -0.03
      NS, respectively. Significant differences in VO(2PEAK) existed between different
      quartiles of BF%, with the exception when VO(2PEAK) was scaled to FFM.
      CONCLUSION:  Our findings document the coexistence of two known risk factors for
      disease at a young age on a population-base and confirms that VO(2PEAK) was
      scaled to FFM represents a body fat independent way of expressing fitness.

PMID- 20670312
TI  - Thrombelastometry-guided thrombolytic therapy in massive pulmonary artery
      embolism.
AB  - We report a case of a patient who suffered a massive pulmonary embolism with
      cardiac arrest on post-operative day 4 after a Whipple operation. Despite
      thrombolytic therapy with the recommended maximal bolus of 50 mg recombinant
      tissue type plasminogen activator (rt-PA), thrombelastometry showed no signs of
      fibrinolysis and cardiogenic shock persisted, after only a transient hemodynamic
      improvement. Not until a repeat bolus of 25 mg rt-PA and an infusion of 50 mg/h
      did thrombelastometry demonstrate complete fibrinolysis. Although only residual
      emboli were seen on computed tomography, the patient died secondary to refractory
      right heart failure. This demonstrates that the standard dosing of thrombolytics
      may fail in a subgroup of patients, and suggests that thrombelastometry may be
      useful for early dose adjustment when standard dosing regimens fail.

PMID- 20670313
TI  - Personnel breathing zone sevoflurane concentration adherence to occupational
      exposure limits in conjunction with filling of vaporisers.
AB  - BACKGROUND: Work place pollution during filling of anaesthetic vaporisers has
      been a matter of concern. We studied personnel breathing zone ambient air
      sevoflurane concentrations during filling of sevoflurane with three different
      filling systems: Quik-FilTM for Abbott and Drager FillTM resp. Easy-FilTM
      adapters for Baxter sevoflurane bottles, referred to as 'Abbott and Baxter
      filling systems'. METHOD: Sequential filling of three vaporisers was performed
      for a 15-min period, once with each of Abbott and Baxter filling systems, by four
      nurses. Ambient-air sevoflurane p.p.m. concentration in the breathing zone was
      continuously measured using a Miran 1a device during filling, and the mean 15 min
      sevoflurane concentration was calculated. RESULTS: All eight measured (4 * 2
      sequences) 15-min mean breathing zone sevoflurane concentrations covering filling
      of three vaporisers were well below the recommended short-term value (STV)
      provided by the Swedish Work Environment Authority (STV 20 p.p.m.). CONCLUSION:
      The breathing zone sevoflurane concentration during filling of sevoflurane with
      Baxter or Abbott filling systems, in an ordinary operating theatre, was found to
      be reassuringly below the Swedish recommended STV (20 p.p.m. average for a 15-min
      period).

PMID- 20670314
TI  - The introductory consensus conference follow-up issue: toward fulfillment of the
      research agendas of prior consensus conferences.

PMID- 20670315
TI  - The relationship between the emergent primary percutaneous coronary intervention
      quality measure and inpatient myocardial infarction mortality.
AB  - BACKGROUND: In the setting of acute ST-segment elevation myocardial infarction
      (STEMI), reperfusion therapy with emergent primary percutaneous coronary
      intervention (PCI) significantly reduces mortality. It is unknown whether a
      hospital's performance on the Centers for Medicare & Medicaid Services (CMS)
      quality metric for time from patient arrival to angioplasty is associated with
      its overall hospital acute myocardial infarction (AMI) mortality rate.
      OBJECTIVES: The objective of this study was to evaluate if hospitals with higher
      performance on the time-to-PCI quality measure are more likely to achieve lower
      mortality for patients admitted for any type of AMI. METHODS: Using merged 2006
      data from the Nationwide Inpatient Sample (NIS), the American Hospital
      Association (AHA) annual survey, and CMS Hospital Compare quality indicator data,
      we examined 69,101 admissions with an International Classification of Diseases,
      Ninth Revision (ICD-9)-coded principal diagnosis of AMI in the 116 hospitals that
      reported more than 24 emergent primary PCI admissions in that year. Hospitals
      were categorized into quartiles according to percentage of admissions in 2006
      that achieved the primary PCI timeliness threshold (time-to-PCI quality measure).
      Using a random effects logistic regression model of inpatient mortality, we
      examined the significance of the hospital time-to-PCI quality measure after
      adjustment for other hospital and individual patient sociodemographic and
      clinical characteristics. RESULTS: The unadjusted inpatient AMI mortality rate at
      the 27 top quartile hospitals was 4.3%, compared to 5.1% at the 32 bottom
      quartile (worst performing) hospitals. The risk-adjusted odds ratio (OR) of
      inpatient death was 0.83 (95% confidence interval [CI] = 0.72 to 0.95), or 17%
      lower odds of inpatient death, among patients admitted to hospitals in the top
      quartile for the time-to-PCI quality measure compared to the case if the
      hospitals were in the bottom 25th percentile. CONCLUSIONS: Hospitals with the
      highest and second highest quartiles of time-to-PCI quality measure had a
      significantly lower overall AMI mortality rate than the lowest quartile
      hospitals. Despite the fact that a minority of all patients with AMI get an
      emergent primary PCI, hospitals that perform this more efficiently also had a
      significantly lower mortality rate for all their patients admitted with AMI. The
      time-to-PCI quality measure in 2006 was a potentially important proxy measure for
      overall AMI quality of care.

PMID- 20670316
TI  - Racial and sex differences in emergency department triage assessment and test
      ordering for chest pain, 1997-2006.
AB  - OBJECTIVES: This study assessed whether sociodemographic differences exist in
      triage assignment and whether these differences affect initial diagnostic testing
      in the emergency department (ED) for patients presenting with chest pain.
      METHODS: A nationally representative ED data sample for all adults (>or=18 years)
      was obtained from the National Hospital Ambulatory Health Care Survey of EDs for
      1997-2006. Weighted logistic regression was used to examine the associations
      between race and presenting symptom, triage assignment, and test ordering,
      adjusting for patient and hospital characteristics. RESULTS: Over 10 years, an
      estimated 78 million visits to the ED presented with a complaint of chest pain.
      Of those presenting with chest pain, African Americans (odds ratio [OR] = 0.70;
      99% confidence interval [CI] = 0.53 to 0.92), Hispanics (OR = 0.74; 99% CI = 0.51
      to 0.99), Medicaid patients (OR = 0.72; 99% CI = 0.54 to 0.94), and uninsured
      patients (OR = 0.65; 99% CI = 0.51 to 0.84) were less likely to be triaged
      emergently. African Americans (OR = 0.86; 99% CI = 0.70 to 0.99), Medicaid
      patients (OR = 0.70; 99% CI = 0.55 to 0.88), and uninsured patients (OR = 0.70;
      99% CI = 0.55 to 0.89) were less likely to have an electrocardiogram (ECG)
      ordered. African Americans (OR = 0.69; 99% CI = 0.49 to 0.97), Medicaid patients
      (OR = 0.67; 99% CI = 0.47 to 0.95), and uninsured patients (OR = 0.66; 99% CI =
      0.44 to 0.96) were less likely to have cardiac enzymes ordered. Similarly,
      African Americans and Hispanics were less likely to have a cardiac monitor and
      pulse oximetry ordered, and Medicaid and uninsured patients were less likely to
      have a cardiac monitor ordered. CONCLUSIONS: Persistent racial, sex, and
      insurance differences in triage categorization and basic cardiac testing exist.
      Eliminating triage disparities may affect "downstream" clinical care and help
      eliminate observed disparities in cardiac outcomes.

PMID- 20670317
TI  - Effect of race and insurance on outcome of pediatric trauma.
AB  - OBJECTIVES: This study sought to determine if insurance or race status affect
      trauma outcomes in pediatric trauma patients. METHODS: Using the National Trauma
      Data Bank (NTDB; v6.2), the following variables were extracted: age (0-17 years),
      payment type (insured, Medicaid/Medicare, or self-pay), race (white,
      Black/African American, or Hispanic), Injury Severity Score (ISS > 8), type of
      trauma (blunt or penetrating), and discharge status (alive or dead). Data were
      analyzed using logistic regression. RESULTS: Of the 70,781 patient visits
      analyzed, 67% were insured, 23% were Medicaid/Medicare, and 10% were self-pay.
      Self-pay patients had higher mortality (11%, compared to Medicaid/Medicare at 5%
      and insured at 4%; p < 0.001). African Americans and Hispanics also had higher
      mortality (7 and 6%) compared to whites (4%; p < 0.001). Self-pay patients more
      likely suffered penetrating trauma than insured patients (12% vs. 4%; p < 0.001),
      and mortality for penetrating trauma self-pay patients was 29%, compared to only
      11% for penetrating trauma insured patients (p < 0.001). The mortality rate
      varied from a low of 3% for insured whites, to 18% for self-pay African
      Americans. Logistic regression (including race, insurance status, injury type,
      and ISS) revealed that African Americans and Hispanics both had an increased risk
      of death compared to whites (African American odds ratio [OR] = 1.37, Hispanic OR
      = 1.20). Medicaid/Medicare patients had a slightly increased risk of death with
      OR = 1.14, but self-pay patients were almost three times more likely to die
      (adjusted OR = 2.92). CONCLUSIONS: After controlling for ISS and type of injury,
      mortality disparity exists for uninsured, African American, and Hispanic
      pediatric trauma patients. Although the reasons for this are unclear, efforts to
      decrease these disparities are needed.

PMID- 20670318
TI  - Characterizing waiting room time, treatment time, and boarding time in the
      emergency department using quantile regression.
AB  - OBJECTIVES: The objective was to characterize service completion times by
      patient, clinical, temporal, and crowding factors for different phases of
      emergency care using quantile regression (QR). METHODS: A retrospective cohort
      study was conducted on 1-year visit data from four academic emergency departments
      (EDs; N = 48,896-58,316). From each ED's clinical information system, the authors
      extracted electronic service information (date and time of registration; bed
      placement, initial contact with physician, disposition decision, ED discharge,
      and disposition status; inpatient medicine bed occupancy rate); patient
      demographics (age, sex, insurance status, and mode of arrival); and clinical
      characteristics (acuity level and chief complaint) and then used the service
      information to calculate patients' waiting room time, treatment time, and
      boarding time, as well as the ED occupancy rate. The 10th, 50th, and 90th
      percentiles of each phase of care were estimated as a function of patient,
      clinical, temporal, and crowding factors using multivariate QR. Accuracy of
      models was assessed by comparing observed and predicted service completion times
      and the proportion of observations that fell below the predicted 10th, 50th, and
      90th percentiles. RESULTS: At the 90th percentile, patients experienced long
      waiting room times (105-222 minutes), treatment times (393-616 minutes), and
      boarding times (381-1,228 minutes) across the EDs. We observed a strong
      interaction effect between acuity level and temporal factors (i.e., time of day
      and day of week) on waiting room time at all four sites. Acuity level 3 patients
      waited the longest across the four sites, and their waiting room times were most
      influenced by temporal factors compared to other acuity level patients. Acuity
      level and chief complaint were important predictors of all phases of care, and
      there was a significant interaction effect between acuity and chief complaint.
      Patients with a psychiatric problem experienced the longest treatment times,
      regardless of acuity level. Patients who presented with an injury did not wait as
      long for an ED or inpatient bed. Temporal factors were strong predictors of
      service completion time, particularly waiting room time. Mode of arrival was the
      only patient characteristic that substantially affected waiting room time and
      treatment time. Patients who arrived by ambulance had shorter wait times but
      longer treatment times compared to those who did not arrive by ambulance. There
      was close agreement between observed and predicted service completion times at
      the 10th, 50th, and 90th percentile distributions across the four EDs.
      CONCLUSIONS: Service completion times varied significantly across the four
      academic EDs. QR proved to be a useful method for estimating the service
      completion experience of not only typical ED patients, but also the experience of
      those who waited much shorter or longer. Building accurate models of ED service
      completion times is a critical first step needed to identify barriers to patient
      flow, begin the process of reengineering the system to reduce variability, and
      improve the timeliness of care provided.

PMID- 20670319
TI  - Efficiency and economic benefits of a payer-based electronic health record in an
      emergency department.
AB  - OBJECTIVES: The objective was to evaluate the use of a payer-based electronic
      health record (P-EHR), which is a clinical summary of a patient's medical and
      pharmacy claims history, in an emergency department (ED) on length of stay (LOS)
      and plan payments. METHODS: A large urban ED partnered with the dominant health
      plan in the region and implemented P-EHR technology in September 2005 for
      widespread use for health plan members presenting to the ED. A retrospective
      observational study design was used to evaluate this previously implemented P
      EHR. Health plan and electronic hospital data were used to identify 2,288 ED
      encounters. Encounters with P-EHR use (n = 779) were identified between September
      1, 2005, and February 17, 2006; encounters from the same health plan (n = 1,509)
      between November 1, 2004, and March 31, 2005, were compared. Outcomes were ED LOS
      and plan payment for the ED encounter. Analyses evaluated the effect of using the
      P-EHR in the ED setting on study outcomes using multivariate regressions and the
      nonparametric bootstrap. RESULTS: After covariate adjustment, among visits
      resulting in discharge (ED-only), P-EHR visits were 19 minutes shorter (95%
      confidence interval [CI] = 5 to 33 minutes) than non-P-EHR visits. Among visits
      resulting in hospitalization, the P-EHR was associated with an average 77-minute
      shorter ED LOS (95% CI = 28 to 126 minutes), compared to non-P-EHR visits. The P
      EHR was associated with an average of $1,560 (95% CI = $43 to $2,910) lower total
      plan expenditures for hospitalized visits. No significant difference in total
      payments was observed among discharged visits. CONCLUSIONS: In the study ED, the
      P-EHR was associated with a significant reduction in ED LOS overall and was
      associated with lower plan payments for visits that resulted in hospitalization.

PMID- 20670320
TI  - The effect of emergency department crowding on length of stay and medication
      treatment times in discharged patients with acute asthma.
AB  - OBJECTIVES: This study sought to determine if emergency department (ED) crowding
      was associated with longer ED length of stay (LOS) and time to ordering
      medications (nebulizers and steroids) in patients treated and discharged with
      acute asthma and to study how delays in ordering may affect the relationship
      between ED crowding and ED LOS. METHODS: A retrospective cohort study was
      performed in adult ED patients aged 18 years and older with a primary
      International Classification of Diseases, 9th Revision (ICD-9), diagnosis of
      asthma who were treated and discharged from two EDs from January 1, 2007, to
      January 1, 2009. Four validated measures of ED crowding (ED occupancy, waiting
      patients, admitted patients, and patient-hours) were assigned at the time of
      triage. The associations between the level of ED crowding and overall LOS and
      time to treatment orders were tested by analyzing trends across crowding
      quartiles, testing differences between the highest and lowest quartiles using
      Hodges-Lehmann distances, and using relative risk (RR) regression for
      multivariable analysis. RESULTS: A total of 1,716 patients were discharged with
      asthma over the study period (932 at the academic site and 734 at the community
      site). LOS was longer at the academic site than the community site for asthma
      patients by 90 minutes (95% confidence interval [CI] = 79 to 101 minutes). All
      four measures of ED crowding were associated with longer LOS and time to
      treatment order at both sites (p < 0.001). At the highest level of ED occupancy,
      patients spent 75 minutes (95% CI = 58 to 93 minutes) longer in the ED compared
      to the lowest quartile of ED occupancy. In addition, comparing the highest and
      lowest quartiles of ED occupancy, time to nebulizer order was 6 minutes longer
      (95% CI = 1 to 13 minutes), and time to steroid order was 16 minutes longer (95%
      CI = 0 to 38 minutes). In the multivariable analysis, the association between ED
      crowding and LOS remained significant. Delays in nebulizer and steroid orders
      explained some, but not all, of the relationship between ED crowding and ED LOS.
      CONCLUSIONS: Emergency department crowding is associated with longer ED LOS (by
      more than 1 hour) in patients who ultimately get discharged with asthma flares.
      Some but not all of longer LOS during crowded times is explained by delays in
      ordering asthma medications.

PMID- 20670321
TI  - Emergency department throughput, crowding, and financial outcomes for hospitals.
AB  - Emergency department (ED) crowding has been identified as a major public health
      problem in the United States by the Institute of Medicine. ED crowding not only
      is associated with poorer patient outcomes, but it also contributes to lost
      demand for ED services when patients leave without being seen and hospitals must
      go on ambulance diversion. However, somewhat paradoxically, ED crowding may
      financially benefit hospitals. This is because ED crowding allows hospitals to
      maximize occupancy with well-insured, elective patients while patients wait in
      the ED. In this article, the authors propose a more holistic model of hospital
      flow and revenue that contradicts this notion and offer suggestions for
      improvements in ED and hospital management that may not only reduce crowding and
      improve quality, but also increase hospital revenues. Also proposed is that
      increased efficiency and quality in U.S. hospitals will require changes in
      systematic microeconomic and macroeconomic incentives that drive the delivery of
      health services in the United States. Finally, the authors address several
      questions to propose mutually beneficial solutions to ED crowding that include
      the realignment of hospital incentives, changing culture to promote flow, and
      several ED-based strategies to improve ED efficiency.

PMID- 20670322
TI  - Emergency Department Sickle Cell Assessment of Needs and Strengths (ED-SCANS), a
      focus group and decision support tool development project.
AB  - OBJECTIVES: A decision support tool may guide emergency clinicians in recognizing
      assessment, analgesic and overall management, and health service delivery needs
      for patients with sickle cell disease (SCD) in the emergency department (ED). We
      aimed to identify data and process elements important in making decisions
      regarding evaluation and management of adult patients in the ED with painful
      episodes of SCD. METHODS: Qualitative methods using a series of focus groups and
      grounded theory were used. Eligible participants included adult clients with SCD
      and emergency physicians and nurses with a minimum of 1 year of experience
      providing care to patients with SCD in the ED. Patients were recruited in
      conjunction with annual SCD meetings, and providers included clinicians who were
      and were not affiliated with sickle cell centers. Groups were conducted until
      saturation was reached and included a total of two patient groups, three
      physician groups, and two nurse groups. Focus groups were held in New York,
      Durham, Chicago, New Orleans, and Denver. Clinician participants were asked the
      following three questions to guide the discussion: 1) what information would be
      important to know about patients with SCD in the ED setting to effectively care
      for them and help you identify patient analgesic, treatment, and referral needs?
      2) What treatment decisions would you make with this information? and 3) What
      characteristics would a decision support tool need to have to make it meaningful
      and useful? Client participants were asked the same questions with rewording to
      reflect what they believed providers should know to provide the best care and
      what they should do with the information. All focus groups were audiotaped and
      transcribed. The constant comparative method was used to analyze the data. Two
      coders independently coded participant responses and identified focal themes
      based on the key questions. An investigator and assistant independently reviewed
      the transcripts and met until the final coding structure was determined. RESULTS:
      Forty-seven individuals participated (14 persons with SCD, 16 physicians, and 17
      nurses) in a total of seven different groups. Two major themes emerged: acute
      management and health care utilization. Major subthemes included the following:
      physiologic findings, diagnostics, assessment and treatment of acute painful
      episodes, and disposition. The most common minor subthemes that emerged included
      past medical history, presence of a medical home (physician or clinic),
      individualized analgesic treatment plan for treatment of painful episodes,
      history of present illness, medical home follow-up available, patient-reported
      analgesic treatment that works, and availability of analgesic prescription at
      discharge. Additional important elements in treatment of acute pain episodes
      included the use of a standard analgesic protocol, need for fluids and
      nonpharmacologic interventions, and the assessment of typicality of pain
      presentation. The patients' interpretation of the need for hospital admission
      also ranked high. CONCLUSIONS: Participants identified several areas that are
      important in the assessment, management, and disposition decisions that may help
      guide best practices for SCD patients in the ED setting.

PMID- 20670323
TI  - 44-55-66-PM, a mnemonic that improves retention of the Ottawa Ankle and Foot
      Rules: a randomized controlled trial.
AB  - OBJECTIVES: Studies have suggested that poor knowledge of the Ottawa Ankle Rules
      (OAR) limits its clinical impact. This study evaluated the ability of a mnemonic
      to improve knowledge of the OAR. METHODS: This was a single-blind randomized
      controlled trial performed among residents and medical students doing a pediatric
      emergency medicine rotation. At baseline, all participants were tested for their
      baseline knowledge of the OAR. The intervention was a standardized information
      sheet providing a mnemonic of the OAR (44-55-66-PM), while control subjects
      received its classic description. Block randomization (medical student vs. type
      of resident) was used. Each participant answered the same questionnaire at the
      end of rotation (3 weeks later) and via a Web-based survey 5 to 9 months
      postrandomization. Main outcome measures were knowledge of the components of the
      ankle rule based on a 13-item criterion grid and the foot rule based on a 10-item
      criterion grid. All questionnaires were marked at the end of the study by two
      reviewers blinded to the randomization. Discrepancies in final scores were
      resolved by consensus. Student's t-test was performed to compare mean scores on
      the evaluation between groups using an intention-to-treat approach. RESULTS:
      Among the 206 eligible participants, 96 medical students and 94 residents were
      recruited and agreed to participate. Primary outcomes were measured in 95% of the
      participants at 3 weeks postrandomization and in 72% on the long-term follow-up.
      Participants in both groups were similar with regard to baseline characteristics
      and prior knowledge of the OAR. Both groups showed improvement in their knowledge
      of the rule during the study period. At mid-term, knowledge of the OAR was
      similar for the ankle components (score for mnemonic 10.9; control 10.2; 95%
      confidence interval [CI] for difference = -0.3 to 1.7) and for the foot (mnemonic
      7.6 vs. control 7.5; 95% CI for difference = -0.7 to 0.9). On the long term,
      randomization to the mnemonic was associated with a better knowledge of the OAR
      as demonstrated by a higher score for the ankle component (mnemonic 10.1 vs.
      control 8.9; 95% CI for difference = 0.6 to 1.8) and for the foot (mnemonic 7.8
      vs. control 6.5; 95% CI for difference = 0.8 to 1.9). CONCLUSIONS: Mid-term
      knowledge of the OAR drastically improved for all participants of the study. The
      use of the mnemonic 44-55-66-PM was associated with a better long-term knowledge
      of the OAR among medical students and residents. The improvement in knowledge of
      the OAR among the control group highlights the importance of using controlled
      trials for studies evaluating knowledge transfer.

PMID- 20670324
TI  - Educational and research advances stemming from the Academic Emergency Medicine
      consensus conference in knowledge translation.
AB  - The 2007 Academic Emergency Medicine (AEM) consensus conference "Knowledge
      Translation in Emergency Medicine" yielded a number of initiatives in both
      education and research that directly reflected the conference's published
      objectives and recommendations. One research initiative, CONCERT, is a national
      consortium of chronic obstructive pulmonary disease (COPD) investigators who set
      forth an effort designed to optimize COPD care through the identification of gaps
      between research and practice in diagnosis and management of the chronic and
      acute care aspects of this disease. In addition to CONCERT, educational programs
      designed to identify barriers to evidence implementation and to develop solutions
      to achieve uptake through multidisciplinary collaboration have emerged that
      reflect the impact of the consensus conference. This article describes these
      initiatives and highlights the potential for future innovative opportunities.

PMID- 20670325
TI  - Virtual reality triage training provides a viable solution for disaster
      preparedness.
AB  - OBJECTIVES: The objective of this study was to compare the relative impact of two
      simulation-based methods for training emergency medicine (EM) residents in
      disaster triage using the Simple Triage and Rapid Treatment (START) algorithm,
      full-immersion virtual reality (VR), and standardized patient (SP) drill.
      Specifically, are there differences between the triage performances and posttest
      results of the two groups, and do both methods differentiate between learners of
      variable experience levels? METHODS: Fifteen Postgraduate Year 1 (PGY1) to PGY4
      EM residents were randomly assigned to two groups: VR or SP. In the VR group, the
      learners were effectively surrounded by a virtual mass disaster environment
      projected on four walls, ceiling, and floor and performed triage by interacting
      with virtual patients in avatar form. The second group performed likewise in a
      live disaster drill using SP victims. Setting and patient presentations were
      identical between the two modalities. Resident performance of triage during the
      drills and knowledge of the START triage algorithm pre/post drill completion were
      assessed. Analyses included descriptive statistics and measures of association
      (effect size). RESULTS: The mean pretest scores were similar between the SP and
      VR groups. There were no significant differences between the triage performances
      of the VR and SP groups, but the data showed an effect in favor of the SP group
      performance on the posttest. CONCLUSIONS: Virtual reality can provide a feasible
      alternative for training EM personnel in mass disaster triage, comparing
      favorably to SP drills. Virtual reality provides flexible, consistent, on-demand
      training options, using a stable, repeatable platform essential for the
      development of assessment protocols and performance standards.

PMID- 20670326
TI  - Community-based participatory research: development of an emergency department
      based youth violence intervention using concept mapping.
AB  - OBJECTIVES: Emergency departments (EDs) see a high number of youths injured by
      violence. In Ontario, the most common cause of injury for youths visiting EDs is
      assault. Secondary prevention strategies using the teachable moment (i.e., events
      that can lead individuals to make positive changes in their lives) are ideal for
      use by clinicians. An opportunity exists to take advantage of the teachable
      moment in the ED in an effort to prevent future occurrences of injury in at-risk
      youths. However, little is known about perceptions of youths, parents, and
      community organizations about such interventions in EDs. The aims of this study
      were to engage youths, parents, and frontline community workers in
      conceptualizing a hospital-based violence prevention intervention and to identify
      outcomes relevant to the community. METHODS: Concept mapping is an innovative,
      mixed-method research approach. It combines structured qualitative processes such
      as brainstorming and group sorting, with various statistical analyses such as
      multidimensional scaling and hierarchical clustering, to develop a conceptual
      framework, and allows for an objective presentation of qualitative data. Concept
      mapping involves multiple structured steps: 1) brainstorming, 2) sorting, 3)
      rating, and 4) interpretation. For this study, the first three steps occurred
      online, and the fourth step occurred during a community meeting. RESULTS: Over 90
      participants were involved, including youths, parents, and community youth
      workers. A two-dimensional point map was created and clusters formed to create a
      visual display of participant ideas on an ED-based youth violence prevention
      intervention. Issues related to youth violence prevention that were rated of
      highest importance and most realistic for hospital involvement included
      mentorship, the development of youth support groups in the hospital, training
      doctors and nurses to ask questions about the violent event, and treating youth
      with respect. Small-group discussions on the various clusters developed job
      descriptions, a list of essential services, and suggestions on ways to create a
      more youth-friendly environment in the hospital. A large-group discussion
      revealed outcomes that participants felt should be measured to determine the
      success of an intervention program. CONCLUSIONS: This study has been the
      springboard for the development of an ED-based youth violence intervention that
      is supported by the community and affected youth. Using information generated by
      youth that is grounded in their experience through participatory research methods
      is feasible for the development of successful and meaningful youth violence
      prevention interventions.

PMID- 20670328
TI  - Failure of intimate partner violence screening among patients with substance use
      disorders.
AB  - OBJECTIVES: This study examined the relationship between substance use disorder
      (SUD) and intimate partner violence (IPV) screening and management practices in
      the emergency department (ED). METHODS: This was a retrospective cohort study of
      adult ED patients presenting to an urban, tertiary care teaching hospital over a
      4-month period. An automated electronic data abstraction process identified
      consecutive patients and retrieved visit characteristics, including results of
      three violence screening questions, demographic data, triage acuity, time of
      visit, and International Classifications of Disease, 9th revision (ICD-9),
      diagnosis codes. Data on management were collected using a standardized
      abstraction tool by two reviewers masked to the study question. Multivariate
      logistic regression was used to determine predictors of screening and management.
      RESULTS: In 10,071 visits, 6,563 violence screens were completed. IPV screening
      was documented in 33.5% of patients with alcohol-related diagnoses (95%
      confidence interval [CI] = 27.7% to 39.3%, chi(2) = 116.78, p < 0.001) and 53.3%
      of patients with drug-related diagnoses (95% CI = 44.3% to 62.3%, chi(2) = 7.69,
      p = 0.006), compared to 66.1% of patients without these diagnoses (95% CI = 65.2%
      to 67.1%). In the multivariate analysis, alcohol (odds ratio [OR] = 0.30, 95% CI
      = 0.22 to 0.40) and drug use (OR = 0.56, 95% CI = 0.38 to 0.83) were associated
      with decreased odds of screening. Of completed screens, 429 (6.5%) were positive,
      but violence was addressed further in only 55.7% of patients. Substance abuse did
      not appear to affect the odds of having positive screens addressed further by
      providers (OR = 1.96, 95% CI = 0.39 to 10.14). CONCLUSIONS: This study found an
      association between SUD and decreased odds of IPV screening. Failure to screen
      for IPV in the setting of substance use may represent a missed opportunity to
      address a critical health issue and be a barrier to successful intervention.

PMID- 20670329
TI  - A brief motivational interview in a pediatric emergency department, plus 10-day
      telephone follow-up, increases attempts to quit drinking among youth and young
      adults who screen positive for problematic drinking.
AB  - OBJECTIVES: Adolescents in their late teens and early 20s have the highest
      alcohol consumption in the United States; binge drinking peaks at age 21-25
      years. Underage drinking is associated with many negative consequences, including
      academic problems and risk of intentional and unintentional injuries. This study
      tested the effectiveness of pediatric emergency department (PED) screening and
      brief intervention to reduce alcohol consumption and associated risks. METHODS: A
      three-group randomized assignment trial was structured to test differences
      between intervention (I) and standard assessed control (AC) groups in alcohol
      consumption and alcohol-related behaviors from baseline to 12 months and to
      compare the AC group with a minimally assessed control (MAC) group to adjust for
      the effect of assessment reactivity on control group behavior. Patients aged 14
      21 years were eligible if they screened positive on the Alcohol Use Disorders
      Identification Test (AUDIT) or for binge drinking or high-risk behaviors. The MAC
      group received a resource handout, written advice about alcohol-related risks,
      and a 12-month follow-up appointment. Patients in the AC group were assessed
      using standardized instruments in addition to the MAC protocol. The I group
      received a peer-conducted motivational intervention, referral to community
      resources and treatment if indicated, and a 10-day booster in addition to
      assessment. Measurements included 30-day self-report of alcohol consumption and
      alcohol-related behaviors, screens for depression and posttraumatic stress
      disorder, and self-report of attempts to quit, cut back, or change conditions of
      use, all repeated at follow-up. Motor vehicle records and medical records were
      also analyzed for changes from baseline to 1-year follow-up. RESULTS: Among 7,807
      PED patients screened, 1,202 were eligible; 853 enrolled (I, n = 283; AC, n =
      284; MAC, n = 286), with a 12-month follow-up rate of 72%. At 12 months, more
      than half of enrollees in Reaching Adolescents for Prevention (RAP) attempted to
      cut back on drinking, and over a third tried to quit. A significantly larger
      proportion of the I group made efforts to quit drinking and to be careful about
      situations when drinking compared to AC enrollees, and there was a numerically
      but not significantly greater likelihood (p = 0.065) among the I group for
      efforts to cut back on drinking. At 3 months, the likelihood of the I group
      making attempts to cut back was almost triple that of ACs. For efforts to quit,
      it was double, and for trying to be careful about situations when drinking, there
      was a 72% increase in the odds ratio (OR) for the I group. Three-month results
      for attempts were sustained at 12 months for quit attempts and efforts to be
      careful. Consumption declined in both groups from baseline to 3 months to 12
      months, but there were no significant between-group differences in alcohol
      related consequences at 12 months or in alcohol-related risk behaviors. We found
      a pattern suggestive of assessment reactivity in only one variable at 12 months:
      the attempt to cut back (73.3% for the I group vs. 64.9% among the AC group and
      54.8% among the MAC group). CONCLUSIONS: Brief motivational intervention resulted
      in significant efforts to change behavior (quit drinking and be careful about
      situations while drinking) but did not alter between-group consumption or
      consequences.

PMID- 20670330
TI  - Integrating Project ASSERT: a screening, intervention, and referral to treatment
      program for unhealthy alcohol and drug use into an urban emergency department.
AB  - OBJECTIVES: The objective was to evaluate the effects of Project Alcohol and
      Substance Abuse Services Education and Referral to Treatment (ASSERT), an
      emergency department (ED)-based screening, brief intervention, and referral to
      treatment program for unhealthy alcohol and other drug use. METHODS: Health
      promotion advocates (HPAs) screened ED patients for alcohol and/or drug problems
      7 days a week using questions embedded in a general health questionnaire.
      Patients with unhealthy drinking and/or drug use received a brief negotiation
      interview (BNI), with the goal of reducing alcohol/drug use and/or accepting a
      referral to a specialized treatment facility (STF), depending on severity of use.
      Patients referred to an STF were followed up at 1 month by phone or contact with
      the STF to determine referral completion and enrollment into the treatment
      program. RESULTS: Over a 5-year period (December 1999 through December 2004),
      22,534 adult ED patients were screened. A total of 10,246 (45.5%) reported
      alcohol consumption in the past 30 days, of whom 5,533 (54%) exceeded the
      National Institute on Alcohol Abuse and Alcoholism (NIAAA) guidelines for low
      risk drinking. Use of at least one illicit drug was reported by 3,530 patients
      (15.7%). Over one-fourth of screened patients received BNIs (6,266, or 27.8%). Of
      these, 3,968 (63%) were referred to an STF. Eighty-three percent of patients were
      followed at 1 month, and 2,159 (65%) had enrolled in a program. Patients who
      received a direct admission to an STF were 30 times more likely to enroll than
      those who were indirectly referred (odds ratio = 30.71; 95% confidence interval =
      18.48 to 51.04). After 3 years, funding for Project ASSERT was fully incorporated
      into the ED budget. CONCLUSIONS: Project ASSERT has been successfully integrated
      into an urban ED. A direct, facilitated referral for patients with alcohol and
      other drug problems results in a high rate of enrollment in treatment programs.

PMID- 20670331
TI  - The association of single nucleotide polymorphism within vascular endothelial
      growth factor gene with systemic lupus erythematosus and lupus nephritis.
AB  - There were no statistically significant difference in allele and genotype
      frequency of the polymorphisms within the vascular endothelial growth factor
      (VEGF) gene (-460 and +405) between 193 systemic lupus erythematosus patients and
      234 healthy controls. However, the +405 GG was significantly associated with
      lupus nephritis (LN) patients with low VEGF mRNA expression and LN with end-stage
      renal disease.

PMID- 20670332
TI  - HLA polymorphism in a Guarani-Indian population from Paraguay and its usefulness
      for the Hispano-Indian admixture study in Paraguay.
AB  - In this study we investigated the human leucocyte antigen-A (HLA-A), -B and DRB1
      polymorphism of Native American population of Paraguay, the Guarani Indians. We
      found that the HLA variability consisted of 5 HLA-A, 7 HLA-B and 6 HLA-DRB1
      groups of alleles and of several specific alleles (B*1504, B*3505, B*3912,
      B*4004, B*5104, DRB1*0411, DRB1*1413) common in other Native American
      populations. The comparison of the HLA polymorphism of the Guaranis from Paraguay
      with the "Mestizos" of Paraguay and the Spaniards showed that the "Mestizos" of
      Paraguay are genetically very distant from the Guarani Indians of Paraguay but
      much more close to the Spaniards. This can be explained, at least in part, by the
      history of the country. Our results are of importance in transplantation, in
      particular in the search for an unrelated donor for a Paraguayan patient
      requiring hematopoietic stem cell transplantation.

PMID- 20670333
TI  - Distribution of ABO and Rh blood groups in Greece: an update.
AB  - The aim of this study was to investigate and evaluate the frequency of the
      antigens classifying the ABO and Rh blood groups in the Greek population. In this
      study the 3.5% were first generation immigrants with both their parents
      immigrants from countries of the USSR, while 1.2% had only one immigrant parent,
      while the other one was Greek. We compared the frequency of distribution of blood
      groups ABO and Rh to previous studies conducted at a time before Greece became
      destination for refugees and immigrants from East and Northeast countries. Blood
      samples were collected from first year medical students. The frequency of
      distribution of the ABO and Rh blood groups was slightly differentiated in
      comparison to previous relevant studies. Significant increase was recorded with
      respect to the emergence of blood group B in the population investigated, and a
      considerable reduction was noted in blood group O. In reference to the remaining
      blood groups, no statistically significant difference was documented. The genetic
      pool and the genetic inventory of the population residing in Greece have been
      modified during the last years potentially due to the first generation
      immigrants. The results of this study could contribute significantly to the
      National Health System in aiding the prediction of percussions of certain
      diseases related to blood groups, as well as the requirement for certain blood
      groups within the blood donation program.

PMID- 20670334
TI  - HLA matching for organ transplantation...why not?

PMID- 20670335
TI  - Is HLA matching useful?

PMID- 20670336
TI  - British Society for Histocompatibility & Immunogenetics and British
      Transplantation Society guidelines for the detection and characterisation of
      clinically relevant antibodies in allotransplantation.
AB  - Ongoing technological developments in antibody detection and characterisation
      allowing relative quantitation of HLA-specific antibody levels, combined with
      crossmatch results, now allow a graded assessment of patient potential donor
      immunological risk for allotransplantation, rather than a simple 'positive' or
      'negative' categorization of crossmatch results. These developments have driven a
      thorough revision of the British Society for Histocompatibility & Immunogenetics
      and British Transplantation Society Guidelines for the Detection and
      Characterisation of Clinically Relevant Antibodies in Allotransplantation. These
      newly published revised Guidelines contain a number of recommendations as to best
      practice for antibody detection and crossmatching for the transplantation of a
      wide range of solid organs and tissues. These recommendations are briefly
      summarized in this article.

PMID- 20670337
TI  - Molecular cloning and expression of a Relish gene in Chinese mitten crab
      Eriocheir sinensis.
AB  - NF-kappaB is a B-cell specific transcription factor that plays crucial roles in
      inflammation, immunity, apoptosis, development and differentiation. In the
      present study, a novel NF-kappaB-like transcription factor Relish was cloned from
      Chinese mitten crab Eriocheir sinensis (designated as EsRelish) by rapid
      amplification of cDNA ends (RACE) technique based on expressed sequence tag
      (EST). The full-length cDNA of EsRelish was of 5034 bp, consisting of a 5'
      untranslated region (UTR) of 57 bp, a 3' UTR of 1335 bp with two mRNA instability
      motifs (ATTTA), a polyadenylation signal sequence (AATAAA) and a poly (A) tail,
      and an open reading frame (ORF) of 3645 bp encoding a polypeptide of 1214 amino
      acids with a calculated molecular mass of 134.8 kDa and a theoretical isoelectric
      point of 5.26. There were a typical Rel homology domain (RHD), two nuclear
      localization signal (NLS) sequences (KR), an inhibitor kappaB (IkappaB)-like
      domain with six ankyrin repeats, a PEST region and a death domain in the deduced
      amino acid sequence of EsRelish. Conserved domain, higher similarity with other
      Rel/NF-kappaBs and phylogenetic analysis suggested that EsRelish was a member of
      the NF-kappaB family. Quantitative real-time RT-PCR was employed to detect the
      mRNA transcripts of EsRelish in different tissues and its temporal expression in
      hemocytes of E. sinensis challenged with Pichia methanolica and Listonella
      anguillarum. The EsRelish mRNA was found to be constitutively expressed in a wide
      range of tissues. It could be mainly detected in the hemocytes, gonad and
      hepatopancreas, and less degree in the gill, muscle and heart. The expression
      level of EsRelish mRNA in hemocytes was up-regulated from at 3, 6, 9 and 12 h
      after P. methanolica challenge. In L. anguillarum challenge, it was up-regulated
      at 9, 12 and 24 h. The results collectively indicated that EsRelish was
      potentially involved in the immune response against fungus and bacteria.

PMID- 20670338
TI  - Routine diagnostic procedures of myelodysplastic syndromes: value of a structural
      blood cell parameter (NEUT-X) determined by the Sysmex XE-2100TM.
AB  - INTRODUCTION: Diagnostic features of myelodysplastic syndromes (MDS) are often
      polymorphic and nonspecific including anemia in most cases. Standard parameters
      provided by an automated analyzer seldom bring any argument for this diagnosis.
      The aim of this study was to investigate whether some structural parameters, not
      routinely provided by SysmexTM XE 2100 analyzer, could help diagnose MDS in a
      simple way, adapted to routine practice. METHODS: Blood samples from 184 MDS
      fully annotated cases and 3545 normal blood count controls were performed with XE
      2100 SysmexTM analyzer. Quantitative and structural parameters were considered.
      RESULTS: We found that the structural neutrophil parameter, NEUT-X, converted
      into a semi-quantitative parameter, the granularity index (GI), could be used as
      a flag for MDS in front of anemia. Negative GI and anemia were able to make
      otherwise unrecognized MDS stand out in routine practice, increasing the number
      of slides addressed to review from 67% to 96%, without leading to a large excess
      of unfounded slide review among non-MDS. CONCLUSION: Including the GI index in
      the routine parameters provided by the Sysmex analyzer could be of major help for
      nonspecialized routine laboratories in detecting MDS.

PMID- 20670339
TI  - Morpho-functional response of the elbow extensor muscles to twelve-week self
      perceived maximal resistance training.
AB  - The aim of this study was to determine morphological and functional changes of
      the elbow extensor muscles in response to a 12-week self-perceived maximal
      resistance training (MRT). Twenty-one healthy sedentary young men were engaged in
      elbow extensor training using isoacceleration dynamometry for 12 weeks with a
      frequency of five sessions per week (five sets of ten maximal voluntarily
      contractions, 1-min rest period between each set). Prior to, at 6 weeks and after
      the training, a series of cross-sectional magnetic resonance images of the upper
      arm were obtained and muscle volumes were calculated. Maximal and endurance
      strength increased (P<0.01) by 15% and 45% at 6 weeks, and by 29% and 70% after
      12 weeks compared with baseline values, while fatigue rate of the elbow extensors
      decreased by 67%. The volume of triceps brachii increased in both arms (P<0.01)
      by 4% at 6 weeks, and by 8% after 12 weeks compared with baseline values (right
      arm--from 487.4 +/- 72.8 cm3 to 505.8 +/- 72.3 cm3 after 6 weeks and 525.3 +/-
      73.7 cm3 after 12 weeks; left arm--from 475.3 +/- 79.1 cm3 to 493.2 +/- 72.7 cm3
      after 6 weeks and 511.3 +/- 77.0 cm3 after 12 weeks). A high correlation was
      found between maximal muscle strength and muscle volume prior (r2 = 0.62) and
      after (r2 = 0.69) the training (P<=0.05). A self-perceived MRT resulted in an
      increase in maximal and endurance strength. Morphological adaptation changes of
      triceps brachii as a result of 12-week specific strength training can explain
      only up to 26% of strength gain.

PMID- 20670340
TI  - Sense of coherence and oral health in dentate adults: findings from the Finnish
      Health 2000 survey.
AB  - AIM: To assess the relationship between sense of coherence (SOC) and oral health,
      and the role of oral health-related behaviours in this relationship. MATERIALS
      AND METHODS: This is a cross-sectional study of 5401 dentate adults who
      participated in the nationally representative Health 2000 Survey in Finland. The
      survey gathered information on SOC, demographic characteristics, education,
      income, pre-existing diabetes, daily smoking, dental attendance, toothbrushing
      frequency and sugar intake frequency. Oral health was assessed through clinical
      outcomes, such as number of teeth, number of decayed teeth and extent of
      periodontal pockets and perceived oral health. RESULTS: A strong SOC was related
      to having more teeth, fewer decayed teeth, lower extent of periodontal pockets
      and good perceived oral health after adjustment for confounders, such as
      demographic and socioeconomic factors (all p0.003). These associations were
      attenuated but remained significant after further adjustment for potential
      mediators (oral health-related behaviours), except for the association of SOC
      with the extent of periodontal pockets, which was fully accounted for by pre
      existing diabetes, oral health-related behaviours and dental plaque (p=0.549).
      CONCLUSION: SOC is positively associated with various aspects of adult oral
      health, in part because of the better oral health-related behaviours among people
      with a strong SOC.

PMID- 20670341
TI  - Vaccination of mice with Porphyromonas gingivalis or Fusobacterium nucleatum
      modulates the inflammatory response, but fails to prevent experimental
      periodontitis.
AB  - AIM: To assess the potential of using vaccination with Porphyromonas gingivalis
      or Fusobacterium nucleatum, in modulating local subcutaneous inflammatory
      response and alveolar bone loss following coinfection with both bacteria.
      MATERIALS AND METHODS: Mice were immunized against either P. gingivalis or F.
      nucleatum. The cytokine response to mixed infection with P. gingivalis and F.
      nucleatum was evaluated using the subcutaneous chamber model. The alveolar bone
      loss induced by oral mixed infection was evaluated by micro-CT using the
      experimental periodontitis model. Serum levels of specific antibodies were
      determined by ELISA. RESULTS: Vaccination with either bacterium produced a
      specific humoral response before infection. Animals immunized against either
      bacteria following a mixed infection with P. gingivalis and F. nucleatum, showed
      decreased TNFalpha (but not IL-1beta) levels as compared with non-immunized
      animals. However, the vaccination did not change the level of mixed infection
      induced alveolar bone loss when compared with non-immunized animals. Six weeks
      following the oral mixed infection, specific antibody titres remained high.
      Furthermore, specific antibodies against the non-immunized bacterium were present
      at high levels. CONCLUSIONS: While vaccination produced specific antibodies and
      suppressed the inflammatory response, it failed to prevent or reduce the
      progression of experimental periodontitis induced by mixed infection with P.
      gingivalis and F. nucleatum.

PMID- 20670342
TI  - Differential effects of TGF-beta and FGF-2 on in vitro proliferation and
      migration of primate retinal endothelial and Muller cells.
AB  - PURPOSE: During retinal development, the pattern of blood vessel formation
      depends upon the combined effects of proliferation and migration of endothelial
      cells, astrocytes and Muller cells. In this study, we investigated the potential
      for transforming growth factor-beta (TGF-beta) and fibroblast growth factor (FGF
      2) to influence this process by regulating proliferation and migration of retinal
      endothelial and macroglial cells. METHODS: We assessed the effects of exogenous
      TGF-beta and FGF-2 on the proliferation and migration of cultured endothelial
      (RF/6A) and Muller cell (MIO-M1) lines. Cell proliferation was measured using a
      MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) colorimetric
      assay over 72 hr. Cell migration was measured using a scratch-wound assay over 72
      hr. RESULTS: Transforming growth factor-beta inhibited the proliferation of
      endothelial and Muller cells and inhibited the migration of Muller cells, but not
      endothelial cells, compared to untreated controls. Conversely, FGF-2 increased
      endothelial cell proliferation but inhibited endothelial cell migration.
      Fibroblast growth factor-2 increased migration of Muller cells but had little
      effect on proliferation except at higher concentrations (20 ng/ml). CONCLUSION:
      Taken together, these observations indicate that TGF-beta and FGF could work in
      concert to inhibit endothelial cell proliferation and migration, respectively;
      this may have implications for establishing and maintaining the avascular zone of
      primate fovea.

PMID- 20670343
TI  - Ruthenium plaque radiation therapy for iris and iridociliary melanomas.
AB  - PURPOSE: To determine the long-term effects of ruthenium-106 plaque radiation
      therapy for iris and iridociliary melanomas in terms of tumour regression and
      complications. METHODS: Between 1 November 1997 and 31 December 2007, 36 patients
      with an iris or iridociliary melanoma were treated with Ruthenium-106 (Ru-106)
      ophthalmic plaque radiation therapy. The median follow-up was 6.5 years with a
      range of 2-11 years. The mean tumour apex dose was 151.5 Gy. Main outcome
      measures were local tumour control and radiation-related ocular complications.
      RESULTS: The mean age of the patients at the time of treatment was 54 years
      (range 14-82). The tumours had a median largest basal dimension of 4.8 mm (range
      3-11) and a prominence of 2.3 mm (range 0.8-5), with a median involvement of
      three clock hours (range 1-6). The tumours were confined to the iris in 14
      patients (39%), extended into the anterior ciliary body in 12 (33%), while the
      anterior ciliary body tumour extended into the iris in ten patients (28%).
      Tumours regressed in all patients (100%) with a mean regression of 80% of the
      original tumour size at 7 years of follow-up. Radiation-related complications
      included corneal erosions on the first postoperative day in nine patients (25%),
      cataract in four of 11 patients free of cataract before treatment (36%) and
      postradiation glaucoma in one patient (3%). Visual acuity of 20/200 or worse was
      present in one of 20 patients (5%) at 6 years of follow-up. Local recurrences
      occurred in two patients (5%), 2 and 5 years after the radiation therapy
      respectively, and both underwent enucleation. Distant metastases occurred in one
      of these enucleated patients (3%) 2 years after treatment. CONCLUSION: Ru-106
      plaque radiation therapy for iris and iridociliary melanoma resulted in good
      local tumour control and preservation of visual acuity with few and treatable
      side-effects.

PMID- 20670344
TI  - Indocyanine green increases light-induced oxidative stress, senescence, and
      matrix metalloproteinases 1 and 3 in human RPE cells.
AB  - PURPOSE: Indocyanine green (ICG) is a commonly used vital dye for macular
      surgery. Recent reports implicate that its use might be associated with less
      favourable results regarding postoperative visual outcome and damage of retinal
      cells, and atrophic degeneration of the retinal pigment epithelium (RPE) has been
      described. This study investigates the effects of ICG on light-induced senescence
      of RPE cells. METHODS: Primary human RPE cells were either pre-incubated with ICG
      in concentrations of 0.005% and 0.05% or not and then exposed to white light.
      After 10 min of irradiation viability, induction of intracellular reactive oxygen
      species (ROS) and senescence-associated beta-galactosidase activity (SA beta-Gal)
      were determined. Expression and secretion of matrix metalloproteinases (MMPs) 1
      and 3 and their mRNA were determined by RT-PCR and ELISA. RESULTS: Light exposure
      decreased RPE cell viability by 46%. Treatment with 0.005% and 0.05% ICG alone
      decreased RPE cell viability by 7% and 21%. In addition, expression of ROS, SA
      beta-Gal, and MMP-1 and 3 was significantly increased. When 0.005% and 0.05% ICG
      treatments were combined with light exposure, viability decreased by 69% and 82%
      compared to the untreated control. Effects on the expression of ROS, SA beta-Gal,
      and MMP-1 and 3 were, depending on the ICG dose, significantly increased when
      cells were pre-incubated with ICG and then illuminated. CONCLUSION: In this
      study, pretreatment with ICG significantly increased light-induced oxidative
      stress and senescence. This might indicate a potential, supplementary mechanism
      that could explain RPE alterations and reduced functional results after ICG
      assisted internal limiting membrane peeling.

PMID- 20670345
TI  - Effect of age on anterior chamber angle configuration in Asians determined by
      anterior segment optical coherence tomography; clinic-based study.
AB  - PURPOSE: To evaluate the distribution of anterior chamber angle (ACA) parameters
      and to assess association of these parameters with age in Asian subjects.
      METHODS:  Four hundred and thirty-nine consecutive Korean subjects aged from 30
      to 89 were enrolled from a university clinic. All participants were scanned using
      anterior segment optical coherence tomography (AS-OCT, Visante, version 2.0). We
      measured ACA parameters such as anterior chamber depth (ACD), angle opening
      distance at 500 and 750MUm (AOD(500,750) ), angle recess area at 500 and 750MUm
      (ARA(500,750) ), trabecular iris space area at 500 and 750MUm (TISA(500,750) ),
      and determined age-related changes in these parameters with use of a linear mixed
      effect model that adjusted for gender, axial length, intraocular pressure, and
      keratometry data. Slopes of ACA parameters as a function of age were determined.
      For various AS-OCT parameters, the normalized slope was calculated by dividing
      the slope by the mean value. RESULTS: All analysed ACA parameters decreased with
      age in both nasal and temporal quadrants. Axial length and keratometry data were
      significant covariates for ACA changes. The slopes of ACD were -0.02396mm/year,
      AOD(500) , ARA(500) , and TISA(500) measured at the temporal angle were 
      0.00634mm/year, -0.0019mm(2) /year, and -0.00177mm(2) /year, respectively. There
      was no age-dependent difference in central corneal thickness (p value; 0.4597)
      Based on the normalized slopes, the AOD showed the steepest slope at both
      temporal and nasal sectors. CONCLUSION: All ACA parameters assessed by AS-OCT,
      which accounted for other ocular biometric parameters, showed significant
      negative slopes with increasing age. These results should be considered when
      assessing changes in the anterior chamber over time.

PMID- 20670346
TI  - Using theories of behaviour change to inform interventions for addictive
      behaviours.
AB  - AIMS: This paper reviews a set of theories of behaviour change that are used
      outside the field of addiction and considers their relevance for this field.
      METHODS: Ten theories are reviewed in terms of (i) the main tenets of each
      theory, (ii) the implications of the theory for promoting change in addictive
      behaviours and (iii) studies in the field of addiction that have used the theory.
      An augmented feedback loop model based on Control Theory is used to organize the
      theories and to show how different interventions might achieve behaviour change.
      RESULTS: Briefly, each theory provided the following recommendations for
      intervention: Control Theory: prompt behavioural monitoring, Goal-Setting Theory:
      set specific and challenging goals, Model of Action Phases: form 'implementation
      intentions', Strength Model of Self-Control: bolster self-control resources,
      Social Cognition Models (Protection Motivation Theory, Theory of Planned
      Behaviour, Health Belief Model): modify relevant cognitions, Elaboration
      Likelihood Model: consider targets' motivation and ability to process
      information, Prototype Willingness Model: change perceptions of the prototypical
      person who engages in behaviour and Social Cognitive Theory: modify self
      efficacy. CONCLUSIONS: There are a range of theories in the field of behaviour
      change that can be applied usefully to addiction, each one pointing to a
      different set of modifiable determinants and/or behaviour change techniques.
      Studies reporting interventions should describe theoretical basis, behaviour
      change techniques and mode of delivery accurately so that effective interventions
      can be understood and replicated.

PMID- 20670347
TI  - Predictors of injury-related and non-injury-related mortality among veterans with
      alcohol use disorders.
AB  - AIMS: To describe the association between alcohol use disorders (AUDs) and
      mortality and to examine risk factors for and all-cause, injury-related and non
      injury-related mortality among those diagnosed with an AUD. SETTING: Department
      of Veterans Affairs, Veterans Health Administration (VHA). PARTICIPANTS: A cohort
      of individuals who received health care in VHA during the fiscal year (FY) 2001
      (n = 3,944,778), followed from the beginning of FY02 through the end of FY06.
      MEASUREMENTS: Demographics and medical diagnoses were obtained from VHA records.
      Data on mortality were obtained from the National Death Index. FINDINGS:
      Controlling for age, gender and race and compared to those without AUDs,
      individuals with AUDs were more likely to die by all causes [hazard ratio (HR) =
      2.30], by injury-related (HR = 3.29) and by non-injury-related causes (HR =
      2.21). Patients with AUDs died 15 years earlier than individuals without AUDs on
      average. Among those with AUDs, Caucasian ethnicity and all mental illness
      diagnoses that were assessed were associated more strongly with injury-related
      than non-injury-related mortality. Also among those with AUDs, individuals with
      medical comorbidity and older age were at higher risk for non-injury related
      compared to injury-related mortality. CONCLUSIONS: In users of a large health
      care system, a diagnosis of an AUD is associated significantly with increased
      likelihood of dying by injury and non-injury causes. Patients with a diagnosis of
      an AUD who die from injury differ significantly from those who die from other
      medical conditions. Prevention and intervention programs could focus separately
      upon selected groups with increased risk for injury or non-injury-related death.

PMID- 20670348
TI  - Initial, habitual and compulsive alcohol use is characterized by a shift of cue
      processing from ventral to dorsal striatum.
AB  - AIMS: During the development of drug addiction, initial hedonic effects decrease
      when substance use becomes habitual and ultimately compulsive. Animal research
      suggests that these changes are represented by a transition from prefrontal
      cortical control to subcortical striatal control and within the striatum from
      ventral to dorsal domains of the striatum, but only limited evidence exists in
      humans. In this study we address this hypothesis in the context of alcohol
      dependence. DESIGN, SETTING AND PARTICIPANTS: Non-abstinent heavy social drinkers
      (n = 21, 5.0 +/- 1.5 drinks/day, 13 of them were alcohol-dependent according to
      DSM-IV) and light social drinkers (n = 10, 0.4 +/- 0.4 drinks/day) were examined.
      MEASUREMENTS: We used a cue-reactivity functional magnetic resonance imaging
      (fMRI) design during which pictures of alcoholic beverages and neutral control
      stimuli were presented. FINDINGS: In the dorsal striatum heavy drinkers showed
      significant higher activations compared to light drinkers, whereas light social
      drinkers showed higher cue-induced fMRI activations in the ventral striatum and
      in prefrontal areas compared to heavy social drinkers [region of interest
      analyses, P < 0.05 false discovery rate (FDR)-corrected]. Correspondingly,
      ventral striatal activation in heavy drinkers correlated negatively with
      obsessive-compulsive craving, and furthermore we found a positive association
      between cue-induced activation in the dorsal striatum and obsessive-compulsive
      craving in all participants. CONCLUSIONS: In line with our hypothesis we found
      higher cue-induced activation of the ventral striatum in social compared to heavy
      drinkers, and higher dorsal striatal activation in heavy drinkers. Increased
      prefrontal activation may indicate that social drinkers activate cortical control
      when viewing alcohol cues, which may prevent the development of heavy drinking or
      alcohol dependence. Our results suggest differentiating treatment research
      depending on whether alcohol use is hedonic or compulsive.

PMID- 20670349
TI  - The importance of family management, closeness with father and family structure
      in early adolescent alcohol use.
AB  - AIMS: To examine the importance of family management, family structure and father
      adolescent relationships on early adolescent alcohol use. DESIGN: Cross-sectional
      data was collected across 30 randomly selected Australian communities stratified
      to represent a range of socio-economic and regional variation. SETTING: Data were
      collected during school time from adolescents attending a broad range of schools.
      PARTICIPANTS: The sample consisted of a combined 8256 students (aged 10-14
      years). MEASUREMENTS: Students completed a web-based survey as part of the
      Healthy Neighbourhoods project. FINDINGS: Family management-which included
      practices such as parental monitoring and family rules about alcohol use-had the
      strongest and most consistent relationship with alcohol use in early adolescence.
      Adolescents reporting higher family management were less likely to have drunk
      alcohol in their life-time, less likely to drink alcohol in the preceding 30 days
      and less likely to have had an alcohol binge. Adolescents reporting emotionally
      close relationships with their fathers were less likely to have drunk alcohol in
      their life-time and less likely to have had an alcohol binge in the preceding
      fortnight. CONCLUSIONS: Findings indicate that family management practices may
      contribute to alcohol abstinence in adolescents. Furthermore, emotionally close
      father-adolescent relationships may also foster abstinence; however, fathers'
      drinking behaviours need to be considered.

PMID- 20670351
TI  - Single graft loss in dual renal transplant recipients: impact of graft placement
      on recipient outcomes.
AB  - We aimed to assess the impact of graft placement in dual renal transplantation on
      the risk for single graft loss and to report recipient outcomes. Between 2004 and
      2007, 55 dual renal transplants were performed at our institution. Allografts
      were placed bilaterally (one in each iliac fossa) in 42 patients and unilaterally
      (both in the same iliac fossa) in 14 patients. Nine recipients (16.4%) underwent
      explantation of a single graft as a consequence of vascular thrombosis designated
      as the SINGLE group, whereas 46 had two functional allografts (DUAL group). There
      was a higher rate of graft loss in case of unilateral placement (n = 5/14)
      compared with bilateral placement (n = 4/41) (35.7% vs. 9.8%, P = 0.035). One
      year glomerular filtration rate was significantly lower in the SINGLE group (29.4
      ml/min/1.73 m(2) vs. 49.4 ml/min/1.73 m(2) in the DUAL group, P < 0.05).
      Significantly, none of the nine recipients of the SINGLE group returned to
      dialysis with a mean follow-up of 34.1 months. Graft survival at 1 year was 100%
      and 97.9% in SINGLE and DUAL groups, respectively. Unilateral placement of both
      allografts is associated with an increased risk of single graft loss and
      therefore lower renal function at 1 year. However, this strategy is safe in
      selected indications.

PMID- 20670350
TI  - Aldose reductase and AGE-RAGE pathways: central roles in the pathogenesis of
      vascular dysfunction in aging rats.
AB  - Aging is inevitably accompanied by gradual and irreversible innate endothelial
      dysfunction. In this study, we tested the hypothesis that accentuation of glucose
      metabolism via the aldose reductase (AR) pathway contributes to age-related
      vascular dysfunction. AR protein and activity levels were significantly increased
      in aged vs. young aortic homogenates from Fischer 344 rats. Immunostaining
      revealed that the principal site of increased AR protein was the aortic
      endothelium as well as smooth muscle cells. Studies revealed that endothelial
      dependent relaxation (EDR) in response to acetylcholine was impaired in aged rats
      compared to young rats and that treatment with the AR inhibitor (ARI) zopolrestat
      significantly improved EDR in aged rats. Methylglyoxal (MG), a key precursor of
      advanced glycation endproducts (AGEs), was significantly increased in the aortas
      of aged rats vs. young rats. Consistent with central roles for AR in generation
      of MG in aging, ARI treatment significantly reduced MG levels in aged rat aorta
      to those in young rats. Treatment of aged rats with soluble(s) RAGE, a soluble
      form of the chief signal transduction receptor for AGEs, RAGE, significantly
      improved EDR in aged rats, thus establishing the contribution of age-related
      increases in AGEs to endothelial dysfunction. These findings reveal that
      significant increases in AR expression and activity in aged rat vasculature
      linked to endothelial dysfunction may be mitigated, at least in part, via ARI and
      that aging-linked increased flux via AR generates AGEs; species which transduce
      endothelial injury consequent to their interaction with RAGE. These data
      demonstrate for the first time that AR mediates aging-related vascular
      dysfunction, at least in part, via RAGE.

PMID- 20670352
TI  - Evaluation of computational methods for the reconstruction of HLA haplotypes.
AB  - Human leukocyte antigen (HLA) haplotypes are frequently evaluated for population
      history inferences and association studies. However, the available typing
      techniques for the main HLA loci usually do not allow the determination of the
      allele phase and the constitution of a haplotype, which may be obtained by a very
      time-consuming and expensive family-based segregation study. Without the family
      based study, computational inference by probabilistic models is necessary to
      obtain haplotypes. Several authors have used the expectation-maximization (EM)
      algorithm to determine HLA haplotypes, but high levels of erroneous inferences
      are expected because of the genetic distance among the main HLA loci and the
      presence of several recombination hotspots. In order to evaluate the efficiency
      of computational inference methods, 763 unrelated individuals stratified into
      three different datasets had their haplotypes manually defined in a family-based
      study of HLA-A, -B, -DRB1 and -DQB1 segregation, and these haplotypes were
      compared with the data obtained by the following three methods: the Expectation
      Maximization (EM) and Excoffier-Laval-Balding (ELB) algorithms using the arlequin
      3.11 software, and the PHASE method. When comparing the methods, we observed that
      all algorithms showed a poor performance for haplotype reconstruction with
      distant loci, estimating incorrect haplotypes for 38%-57% of the samples
      considering all algorithms and datasets. We suggest that computational haplotype
      inferences involving low-resolution HLA-A, HLA-B, HLA-DRB1 and HLA-DQB1
      haplotypes should be considered with caution.

PMID- 20670353
TI  - Ex vivo expansion of natural killer cells with high cytotoxicity by K562 cells
      modified to co-express major histocompatibility complex class I chain-related
      protein A, 4-1BB ligand, and interleukin-15.
AB  - A large number of natural killer (NK) cells with high function are expected to
      generate especially in tumor adoptive immunotherapy. Here K562 cells were
      genetically modified to co-express major histocompatibility complex class I chain
      related protein A (MICA), 4-1BB ligand, and IL-15, called K562-MICA-4-1BBL-IL-15.
      The modified K562 cells not only promoted activation, proliferation, and survival
      of NK cells, but also enhanced NK cell cytotoxicity. In long-term culture tests,
      K562-MICA-4-1BBL-IL-15 cells stimulated NK cell to expand mean 550 folds in 24
      day culture and to cover from 14.8% of total peripheral blood monoclonal
      lymphocytes on day 1 to 86.7% on day 24. Prevalent NK cells after expansion
      enhanced the ability of killing targets and producing interferon gamma (IFN
      gamma), and kept high expression of activating receptors. The results indicated
      that K562-MICA-4-1BBL-IL-15 cells would be developed for expansion of NK cells ex
      vivo and may have important implications for clinical immunotherapy.

PMID- 20670354
TI  - Polymorphism of HLA class II genes in Berbers from Southern Tunisia.
AB  - In this study, the HLA-DRB1 and -DQB1 molecular diversity of two Berber-speaking
      populations of Southern Tunisia was analysed. Genetic comparisons indicate that
      both populations exhibit peculiar profiles for HLA-DRB1, as they diverge
      significantly from most other North Africans, while being highly diversified. At
      the opposite, they are much less differentiated from neighbouring populations
      according to the HLA-DQB1 polymorphism. Overall, the HLA class II genetic
      structure of Arab and Berber-speaking populations from Tunisia, and of North
      Africa as a whole, is complex and cannot be simply explained by geographic or
      linguistic differentiations. The present North African genetic pool has probably
      been shaped by both genetic drift and the contribution of genetically
      heterogeneous populations during the history of settlement of North Africa.

PMID- 20670355
TI  - Diversity of killer cell immunoglobulin-like receptor genes in Indonesian
      populations of Sumatra, Sulawesi and Moluccas Islands.
AB  - Killer immunoglobulin-like receptors (KIRs) regulate the activity of natural
      killer and T cells through interaction with specific human leukocyte antigen
      (HLA) molecules on target cells. Like HLA class I genes that are characterised by
      extreme allelic polymorphism, KIR genes are diverse and vary in both gene content
      and allelic polymorphism. Population studies conducted over the last several
      years have showed that KIR gene frequencies (GF) and genotype content vary among
      different ethnic groups, indicating the extent of KIR diversity. Some studies
      have also shown the effect of the presence or absence of specific KIR genes in
      human disease. We have recently reported the distribution of KIR genes in
      populations from Java (Central Javanese and the Sundanese of West Java), East
      Timor (Timorese), Kalimantan provinces of Indonesian Borneo (Dayaks) and Irian
      Jaya (Western half of the island of New Guinea; Melanese). We here extend
      analysis of the KIR genes in populations from North Sulawesi (Minahasans), West
      Sumatra (Minangs) and Moluccas Islands. All 16 KIR genes were observed in all
      three populations. Variation in GF between populations was observed, except for
      the KIR2DL4, KIR3DL2, KIR3DL3 and KIR3DP1 genes, which were present in every
      individual tested. When comparing KIR GF between populations, both principal
      component analysis and phylogenetic tree analyses showed a close relationship
      between Minahasan and Moluccan populations that are clustered with Timorese in
      the same clade. The Minang tribe lies between the Javanese/Kalimantan and the
      Timorese/Minahasan/Moluccan clades, whereas Irianese show the greatest genetic
      distances from other Indonesian populations. The results correspond well with the
      history of migration in Indonesia and will contribute to the understanding of the
      genetic as well as the geographic history of the region.

PMID- 20670356
TI  - The polymorphism of the Knops blood group system among five Chinese ethnic
      groups.
AB  - AIMS/OBJECTIVE: This work aims to explain the complexity of the Knops blood group
      system in the Chinese population. BACKGROUND: The Knops blood group system
      consists of antigens encoded by CR1 gene exon 29. METHODS: A total of 281
      individuals from the Han, Uigur, Tu, Lisu and Dong ethnic groups were studied.
      The coding region of the CR1 gene of 11 Han donors was analysed using reverse
      transcription-polymerase chain reaction (PCR) and sequencing. CR1 gene exon 29 in
      the 39 samples was analysed through genomic DNA sequencing. According to the
      sequencing result, a PCR-sequence-specific primers system was designed to screen
      the A4646G and A4870G alleles in the Chinese population. RESULTS: Twelve single
      nucleotide polymorphisms (SNPs) were observed in the coding region of the CR1
      gene in the Han population. Two SNPs (A4646G and A4870G) were detected in the CR1
      gene exon 29. The 4646G allele was found only in the Uigur and Tu ethnic groups,
      in which the allele frequencies were 0.11 and 0.06, respectively. The frequencies
      of the 4870A allele in the Han, Uigur, Tu, Lisu and Dong ethnic groups were 0.82,
      0.83, 0.82, 0.57 and 0.57, respectively. CONCLUSIONS: The CR1 gene in the Chinese
      people is more conservative than that in the Caucasian or African people.
      Different Chinese ethnic groups may have their own different CR1 gene
      characteristics. The existence of 4646G in the Uigur and Tu ethnic groups
      suggests that both may carry certain Caucasian characteristics in the CR1 gene.
      The frequency of 4870G in the Lisu and Dong ethnic groups implies possible
      incidence of evolutionary pressure similar to what the Africans had experienced.

PMID- 20670357
TI  - Post-transplant lymphoproliferative disorder resembling Wilms tumor. Diagnostic
      dilemma: renal biopsy or nephrectomy?
AB  - Post-transplant lymphoproliferative disorder is a life-threatening neoplasm that
      can occur after orthotopic liver transplant. We report a 14-month-old female
      status-post OLT with an atypical presentation of PTLD as a solitary renal mass.
      At eight-wk post-transplant, she presented with elevated transaminases, CMV
      counts (73,000 copies/mL), and EBV counts (35,000 copies/mL). CT scan revealed a
      solid heterogeneously enhancing right renal mass measuring 2.6 * 2.4 * 3.3 cm.
      The radiological diagnosis was Wilms tumor, although PTLD could not be excluded.
      Complete resection of a Wilms tumor is potentially curative. A needle biopsy
      would upstage the malignancy and result in radiochemotherapy that is deleterious
      to a liver graft. The mass was not amenable to partial nephrectomy. A total
      nephrectomy, given life-long nephrotoxic immunosuppressants, was an unfavorable
      option. Thus, needle biopsy was performed. Histology confirmed monoclonal, EBV
      associated PTLD and diffuse large B-cell lymphoma. Her therapy included
      immunosuppression reduction, cyclophosphamide, steroids, and anti-CD20 monoclonal
      antibody. Concomitantly, she received Cytogam and gancyclovir. Complete remission
      was achieved three months after chemotherapy. This case illustrates that young
      age, CMV infection, and EBV infection are strong risk factors for PTLD. With such
      risk factors present, any mass or lesion in a solid organ transplant patient
      should be considered PTLD until proven otherwise.

PMID- 20670358
TI  - Induction of phlorotannins during UV exposure mitigates inhibition of
      photosynthesis and DNA damage in the kelp Lessonia nigrescens.
AB  - Phlorotannins of brown algae are multifunctional compounds with putative roles in
      herbivore deterrence, antioxidation and as primary cell wall components. Due to
      their peripheral localization and absorption at short wavelengths, a
      photoprotective role is suggested. We examined the induction of phlorotannins by
      artificial UV radiation in the intertidal kelp Lessonia nigrescens and whether
      they attenuate the inhibition of photosynthesis and DNA damage, two major
      detrimental effects of UV. The soluble and cell wall-bound fractions of
      phlorotannins were quantified in blades collected in summer and winter. Major
      findings were that (1) the synthesis of phlorotannins (both forms) was induced by
      UV only in summer; (2) the induction was fast (within 3 days); and (3) there was
      a positive relationship between of the contents of insoluble phlorotannins and
      the suppression of photoinhibition and DNA damage, measured as formation of
      cyclobutane pyrimidine dimers and 6-4 photoproducts. Overall, the photoprotective
      role of phlorotannins appears to respond to an interplay between the external UV
      stimulus, seasonal acclimation and intrinsic morpho-functional processes. In
      summer, when algae are naturally exposed to high UV irradiances, soluble
      phlorotannins are induced, while their transition to insoluble phlorotannins
      could be related with the growth requirements, as active blade elongation occurs
      during this season.

PMID- 20670359
TI  - Transition metal ions or acid-induced suppression of photoinduced proton transfer
      and electron transfer reaction in 5-(4-fluorophenyl)-2-hydroxypyridine: a
      molecule of dual mode fluorosensitivity.
AB  - The photophysical properties of 5-(4-fluorophenyl)-2-hydroxypyridine (FP2HP) at
      different pH and its fluorescence response toward different transition metal ions
      have been studied by steady-state absorption and emission spectroscopy in
      combination with quantum chemical calculations. Although keto-enol
      tautomerization is observed in the excited state, the molecule is weakly
      fluorescent due to the presence of electron-rich nitrogen atom and relatively
      electron-deficient fluorine atom, which may lead to photoinduced electron
      transfer process. In the presence of the transition metal ions, such as Zn(2+) ,
      Cd(2+) , Hg(2+) , etc., the studied molecule exhibits changes in its absorption
      and emission properties. The present system shows fluorescence enhancement
      instead of usual quenching in presence of the transition metal ions, such as
      Fe(2+) and Cu(2+) . Spectral observation leads to the interpretation that this
      structurally simple molecule can be effectively utilized as a chelation-enhanced
      fluorescence-based chemosensor for the detection of transition metal ions. The
      experimental findings corroborate well with theoretical calculations at Hartree
      Fock level using 6-31G** and lanl2dz basis sets.

PMID- 20670360
TI  - Effects of different doses of low power continuous wave he-ne laser radiation on
      some seed thermodynamic and germination parameters, and potential enzymes
      involved in seed germination of sunflower (Helianthus annuus L.).
AB  - In this study, water-soaked seeds of sunflower were exposed to He-Ne laser
      irradiation of different energies to determine whether or not He-Ne laser
      irradiation caused changes to seed thermodynamic and germination parameters as
      well as effects on the activities of germination enzymes. The experiment
      comprised four energy levels: 0 (control), 100, 300 and 500mJ of laser energy and
      each treatment replicated four times arranged in a completely randomized design.
      The experimentation was performed under the greenhouse conditions in the net
      house of the Department of Botany, University of Agriculture, Faisalabad. The
      seed thermodynamic parameters were calculated according to seed germination
      thermograms determined with a calorimeter at 25.8 degrees C for 72h. Various
      thermodynamic parameters of seed (DeltaH, (DeltaS)(e), (DeltaS)(c), (DeltaS)(e)
      /Deltat and (DeltaS)(c) /Deltat) were affected significantly due to presowing
      laser treatment. Significant changes in seed germination parameters and enzyme
      activities were observed in seeds treated with He-Ne laser. The He-Ne laser seed
      treatment resulted in increased activities of amylase and protease. These results
      indicate that the low power continuous wave He-Ne laser light seed treatment has
      considerable biological effects on seed metabolism. This seed treatment technique
      can be potentially employed to enhance agricultural productivity.

PMID- 20670361
TI  - Enhanced bactericidal activity of modified titania in sunlight against
      Pseudomonas aeruginosa, a water-borne pathogen.
AB  - Photocatalyst-mediated inactivations generate reactive oxygen species and OH
      radicals, which induce oxidative destruction of membrane integrity, causing
      damage to membrane phospholipids of gram negative bacteria like Pseudomonas
      aeruginosa. Nanosized TiO(2) was synthesized by gel to crystalline conversion and
      Zr-doped TiO(2) was synthesized by pulverization using appropriate precursor. The
      doped nanocrystals retained the anatase phase with a marginal increase in
      crystallite size, averaging at 25nm. SEM-EDX analysis of the doped sample depicts
      the substantial growth of grain size with 1.33 atomic weight % of zirconium. The
      created electron states in the doped sample act as charge carrier traps
      suppressing recombination which later detraps the same to the surface of the
      catalyst causing enhanced interfacial charge transfer. Zr-doped TiO(2) at the
      molecular scale exhibits better photocatalytic activity with lower bandgap energy
      that can respond to visible light. The redshift caused by the dopants in
      absorption spectra of TiO(2) facilitated the nonintrinsic sample to exhibit
      nearly 2-fold enhancement of photoinactivation in sunlight. Extent of
      photoinactivation of P. aeruginosa was observed to be complete (100%) within
      150min of sunlight exposure in the presence of modified TiO(2) .

PMID- 20670362
TI  - Inactivation of food-borne spoilage and pathogenic micro-organisms on the surface
      of a photoactive polymer.
AB  - The photodynamic action of a novel photoactive polymer comprising covalently
      bound anthraquinone (AQ) moieties was evaluated after developing a methodology to
      reliably immobilize viable micro-organisms onto polymer film surfaces. The
      survival of Escherichia coli, Bacillus cereus (vegetative cells and spores),
      Fusarium oxysporum and Saccharomyces cerevisiae microbes inoculated on the
      surface of inert polymeric substrates was assessed to determine the effect of
      inoculum composition, drying rate and exposure to ultraviolet (UV-A) radiation.
      Their survival was highly dependent on microbial genus, with E. coli consistently
      displaying markedly shorter survival times than the other microbes, and B. cereus
      spores being the most resistant. Inoculation of the microbes onto the surface of
      the photoactive polymer films, followed by exposure to UV-A radiation,
      dramatically accelerated the inactivation of all microbial types studied compared
      with their survival on the surface of inert polymer substrates. Simultaneous
      exposure to both oxygen and UV-A radiation is required to affect cell survival,
      which is consistent with this effect most likely originating from the
      photoinduced production of singlet oxygen by the photoactive polymer. These
      results provide further compelling evidence that singlet oxygen produced
      exogenously by this photoactive polymeric substrate can successfully inactivate a
      broad spectrum of microbes on the substrate's surface.

PMID- 20670363
TI  - MHC-dependent survival in a wild population: evidence for hidden genetic benefits
      gained through extra-pair fertilizations.
AB  - Females should prefer to be fertilized by males that increase the genetic quality
      of their offspring. In vertebrates, genes of the major histocompatibility complex
      (MHC) play a key role in the acquired immune response and have been shown to
      affect mating preferences. They are therefore important candidates for the link
      between mate choice and indirect genetic benefits. Higher MHC diversity may be
      advantageous because this allows a wider range of pathogens to be detected and
      combated. Furthermore, individuals harbouring rare MHC alleles might better
      resist pathogen variants that have evolved to evade common MHC alleles. In the
      Seychelles warbler, females paired with low MHC-diversity males elevate the MHC
      diversity of their offspring to levels comparable to the population mean by
      gaining extra-pair fertilizations. Here, we investigate whether increased MHC
      diversity results in higher life expectancy and whether there are any additional
      benefits of extra-pair fertilizations. Our 10-year study found a positive
      association between MHC diversity and juvenile survival, but no additional
      survival advantage of extra-pair fertilizations. In addition, offspring with a
      specific allele (Ase-ua4) had a fivefold longer life expectancy than offspring
      without this allele. Consequently, the interacting effects of sexual selection
      and pathogen-mediated viability selection appear to be important for maintaining
      MHC variation in the Seychelles warbler. Our study supports the prediction that
      MHC-dependent extra-pair fertilizations result in genetic benefits for offspring
      in natural populations. However, such genetic benefits might be hidden and not
      necessarily apparent in the widely used fitness comparison of extra- and within
      pair offspring.

PMID- 20670364
TI  - Population history in Arabidopsis halleri using multilocus analysis.
AB  - A. halleri is a psuedometallophyte with a patchy distribution in Europe and is
      often spread by human activity. To determine the population history and whether
      this history is consistent with potential human effects, we surveyed nucleotide
      variation using 24 loci from 12 individuals in a large A. halleri population. The
      means of total and silent nucleotide variation (theta(W)) are within the range
      expected for the species. The population genetic neutrality tests Tajima's D and
      Wall's B had significant composite results rejecting panmixia, and Approximate
      Bayesian Computation analysis revealed that a subdivision model better explained
      the variation than the standard neutral model, refugia (or admixture), bottleneck
      or change of population size models. A categorical regression analysis further
      supports the subdivision model, and under the subdivision model, the neutrality
      tests are no longer significant. The best support was for two source populations,
      a situation consistent with the mixing of two populations possibly mediated by
      human activity. This scenario might limit the genetic diversity and adaptive
      potential of the population. The non-neutral population variation described here
      should be considered in bioinformatic searches for adaptation.

PMID- 20670365
TI  - Genetic and sexual separation between insect resistant and susceptible Barbarea
      vulgaris plants in Denmark.
AB  - Co-evolution between herbivores and plants is believed to be one of the processes
      creating Earth's biodiversity. However, it is difficult to disentangle to what
      extent diversification is really driven by herbivores or by other historical
      geographical processes like allopatric isolation. In the cruciferous plant
      Barbarea vulgaris, some Danish individuals are resistant to herbivory by flea
      beetles (Phyllotreta nemorum), whereas others are not. The flea beetles are, in
      parallel, either resistant or susceptible to the plants defenses. To understand
      the historical-evolutionary framework of these interactions, we tested how
      genetically divergent resistant and susceptible plants are, using microsatellite
      markers. To test whether they are reproductively fully compatible, resistant and
      susceptible plants were grown intermixed in an outdoor experiment, and the
      paternity of open-pollinated offspring was determined by analysis of molecular
      markers. Resistant and susceptible Danish plants were genetically strongly
      differentiated and produced significantly fewer hybrids than expected from random
      mating or nearest neighbour mating. Our results suggest that the two types belong
      to different evolutionary lineages that have been (partly) isolated at some time,
      during which genetic and reproductive divergence evolved. A parsimonious scenario
      could be that the two plant types were isolated in different refugia during the
      previous ice age, from which they migrated into and met in Denmark and possibly
      neighbouring regions. If so, resistance and susceptibility has for unknown
      reasons become associated with the different evolutionary lineages.

PMID- 20670366
TI  - Multiple Pleistocene refugia and Holocene range expansion of an abundant
      southwestern American desert plant species (Melampodium leucanthum, Asteraceae).
AB  - Pleistocene climatic fluctuations had major impacts on desert biota in
      southwestern North America. During cooler and wetter periods, drought-adapted
      species were isolated into refugia, in contrast to expansion of their ranges
      during the massive aridification in the Holocene. Here, we use Melampodium
      leucanthum (Asteraceae), a species of the North American desert and semi-desert
      regions, to investigate the impact of major aridification in southwestern North
      America on phylogeography and evolution in a widespread and abundant drought
      adapted plant species. The evidence for three separate Pleistocene refugia at
      different time levels suggests that this species responded to the Quaternary
      climatic oscillations in a cyclic manner. In the Holocene, once differentiated
      lineages came into secondary contact and intermixed, but these range expansions
      did not follow the eastwardly progressing aridification, but instead occurred
      independently out of separate Pleistocene refugia. As found in other desert
      biota, the Continental Divide has acted as a major migration barrier for M.
      leucanthum since the Pleistocene. Despite being geographically restricted to the
      eastern part of the species' distribution, autotetraploids in M. leucanthum
      originated multiple times and do not form a genetically cohesive group.

PMID- 20670367
TI  - Heterozygosity of the Yellowstone wolves.

PMID- 20670368
TI  - No evidence for Z-chromosome rearrangements between the pied flycatcher and the
      collared flycatcher as judged by gene-based comparative genetic maps.
AB  - Revealing the genetic basis of reproductive isolation is fundamental for
      understanding the speciation process. Chromosome speciation models propose a role
      for chromosomal rearrangements in promoting the build up of reproductive
      isolation between diverging populations and empirical data from several animal
      and plant taxa support these models. The pied flycatcher and the collared
      flycatcher are two closely related species that probably evolved reproductive
      isolation during geographical separation in Pleistocene glaciation refugia.
      Despite the short divergence time and current hybridization, these two species
      demonstrate a high degree of intrinsic post-zygotic isolation and previous
      studies have shown that traits involved in mate choice and hybrid viability map
      to the Z-chromosome. Could rearrangements of the Z-chromosome between the species
      explain their reproductive isolation? We developed high coverage Z-chromosome
      linkage maps for both species, using gene-based markers and large-scale SNP
      genotyping. Best order maps contained 57-62 gene markers with an estimated
      average density of one every 1-1.5 Mb. We estimated the recombination rates in
      flycatcher Z-chromosomes to 1.1-1.3 cM/Mb. A comparison of the maps of the two
      species revealed extensive co-linearity with no strong evidence for chromosomal
      rearrangements. This study does therefore not provide support the idea that sex
      chromosome rearrangements have caused the relatively strong post-zygotic
      reproductive isolation between these two Ficedula species.

PMID- 20670369
TI  - Relation between D-dimer level, venous valvular reflux and the development of
      post-thrombotic syndrome after deep vein thrombosis.
AB  - BACKGROUND: The pathophysiology of post-thrombotic syndrome (PTS) is postulated
      to involve persistent venous obstruction and venous valvular reflux. OBJECTIVE:
      To study the association between D-dimer level, valvular reflux and the PTS in a
      well-defined cohort of deep vein thrombosis (DVT) patients. METHODS: Consecutive
      patients with acute symptomatic DVT were recruited at eight centers and were
      followed for 24months. D-dimer was measured at 4months. A standardized ultrasound
      assessment for popliteal valvular reflux was performed at 12months. Using the
      Villalta scale, patients were assessed for PTS during follow-up by evaluators who
      were unaware of D-dimer or reflux results. RESULTS: Three hundred and eighty
      seven patients were recruited; of these, 305 provided blood samples for D-dimer
      and 233 had a 12-month reflux assessment. PTS developed in 45.1% of subjects.
      Mean D-dimer was significantly higher in patients with vs. without PTS (712.0 vs.
      444.0MUgL(-1) ; P=0.02). In logistic regression analyses adjusted for warfarin
      use at the time of D-dimer determination and risk factors for PTS, D-dimer level
      significantly predicted PTS (P=0.03); when stratifying for warfarin use at the
      time of blood draw, adjusted odds ratio (OR) for developing PTS per unit
      difference in log D-dimer was 2.33 (95% CI 0.89, 6.10) in those not on warfarin
      vs. 1.25 (95% CI 0.87, 1.79) in those on warfarin. Ipsilateral reflux was more
      frequent in patients with moderate-to-severe PTS than in patients with mild PTS
      (65% vs. 40%, respectively; P=0.01) and was independently associated with
      moderate-to-severe PTS in logistic regression analyses (P=0.01). CONCLUSION: D
      dimer levels, measured 4months after DVT in patients not on warfarin, are
      associated with subsequent development of PTS. Venous valvular reflux is
      associated with moderate-to-severe PTS.

PMID- 20670370
TI  - Differential phosphorylation of myosin light chain (Thr)18 and (Ser)19 and
      functional implications in platelets.
AB  - BACKGROUND: Myosin IIA is an essential platelet contractile protein that is
      regulated by phosphorylation of its regulatory light chain (MLC) on residues
      (Thr)18 and (Ser)19 via the myosin light chain kinase (MLCK). OBJECTIVE: The
      present study was carried out to elucidate the mechanisms regulating MLC (Ser)19
      and (Thr)18 phosphorylation and the functional consequence of each
      phosphorylation event in platelets. RESULTS: Induction of 2MeSADP-induced shape
      change occurs within 5s along with robust phosphorylation of MLC (Ser)19 with
      minimal phosphorylation of MLC (Thr)18. Selective activation of G(12/13) produces
      both slow shape change and comparably slow MLC (Thr)18 and (Ser)19
      phosphorylation. Stimulation with agonists that trigger ATP secretion caused
      rapid MLC (Ser)19 phosphorylation while MLC (Thr)18 phosphorylation was
      coincident with secretion. Platelets treated with p160(ROCK) inhibitor Y-27632
      exhibited a partial inhibition in secretion and had a substantial inhibition in
      MLC (Thr)18 phosphorylation without effecting MLC (Ser)19 phosphorylation. These
      data suggest that phosphorylation of MLC (Ser)19 is downstream of Gq/Ca(2+) 
      dependent mechanisms and sufficient for shape change, whereas MLC (Thr)18
      phosphorylation is substantially downstream of G(12/13) -regulated Rho kinase
      pathways and necessary, probably in concert with MLC (Ser)19 phosphorylation, for
      full contractile activity leading to dense granule secretion. Overall, we suggest
      that the amplitude of the platelet contractile response is differentially
      regulated by a least two different signaling pathways, which lead to different
      phosphorylation patterns of the myosin light chain, and this mechanism results in
      a graded response rather than a simple on/off switch.

PMID- 20670371
TI  - The 'Royal disease'.

PMID- 20670372
TI  - What is vinculin needed for in platelets?
AB  - Summary.  BACKGROUND: Vinculin links integrins to the cell cytoskeleton by virtue
      of its binding to proteins such as talin and F-actin. It has been implicated in
      the transmission of mechanical forces from the extracellular matrix to the
      cytoskeleton of migrating cells. Vinculin's function in platelets is unknown.
      OBJECTIVE: To determine whether vinculin is required for the functions of
      platelets and their major integrin, alpha(IIb) beta(3) . METHODS: The murine
      vinculin gene (Vcl) was deleted in the megakaryocyte/platelet lineage by breeding
      Vcl fl/fl mice with Pf4-Cre mice. Platelet and integrin functions were studied in
      vivo and ex vivo. RESULTS: Vinculin was undetectable in platelets from Vcl fl/fl
      Cre(+) mice, as determined by immunoblotting and fluorescence microscopy.
      Vinculin-deficient megakaryocytes exhibited increased membrane tethers in
      response to mechanical pulling on alpha(IIb) beta(3) with laser tweezers,
      suggesting that vinculin helps to maintain membrane cytoskeleton integrity.
      Surprisingly, vinculin-deficient platelets displayed normal agonist-induced
      fibrinogen binding to alpha(IIb) beta(3) , aggregation, spreading, actin
      polymerization/organization, clot retraction and the ability to form a
      procoagulant surface. Furthermore, vinculin-deficient platelets adhered to
      immobilized fibrinogen or collagen normally, under both static and flow
      conditions. Tail bleeding times were prolonged in 59% of vinculin-deficient mice.
      However, these mice exhibited no spontaneous bleeding and they formed occlusive
      platelet thrombi comparable to those in wild-type littermates in response to
      carotid artery injury with FeCl(3) . CONCLUSION: Despite promoting membrane
      cytoskeleton integrity when mechanical force is applied to alpha(IIb) beta(3) ,
      vinculin is not required for the traditional functions of alpha(IIb) beta(3) or
      the platelet actin cytoskeleton.

PMID- 20670373
TI  - PPAR activation has dichotomous control on the expression levels of cytosolic and
      secretory phospholipase A2 in astrocytes; inhibition in naive, untreated cells
      and enhancement in LPS-stimulated cells.
AB  - Despite the importance of cytosolic phospholipase A(2) type IVA (cPLA(2)) and
      secretory PLA(2) (sPLA(2)) in physiological and pathological responses of
      astrocytes in inflammatory conditions, the regulation of the expression of these
      genes is still unclear. Both genes have peroxisome proliferator-activated
      receptors (PPAR) binding sites in their promoters. The role of synthetic PPAR
      agonists in the regulation of gene expression in naive and lipopolysaccharide
      (LPS)-stimulated rat astrocytes in culture was investigated. Exposure to LPS
      resulted in a time-dependent, fourfold transient increase of sPLA(2) expression,
      with maximum at 4 h; cPLA(2) expression was notably increased after 16-h LPS
      stimulation. Using selective PPARalpha, PPARbeta/delta, and PPARgamma agonists,
      we found that expression of both cPLA(2) and sPLA(2) is under PPAR control, but
      with different isotypes sensitivity. In naive astrocytes, all three PPAR agonists
      significantly suppressed the expression of sPLA(2), while only PPARalpha and
      PPARgamma activation suppressed cPLA(2) expression. Astonishingly, simultaneous
      addition of LPS with PPAR agonists evoked the opposite effect. All three PPAR
      agonists induced potentiation of cPLA(2) expression level. Potentiation of
      sPLA(2) expression was induced only by simultaneous addition of LPS with
      PPARgamma agonist. By knockdown of PPARalpha, PPARbeta/delta, and PPARgamma, we
      confirmed the involvement of PPAR-dependent pathways. The important novelty of
      our findings is that both sPLA(2) and cPLA(2) are under dichotomous control of
      PPARs: suppression in naive control cells, but induction in LPS-stimulated
      astrocytes.

PMID- 20670374
TI  - GIGYF2 is present in endosomal compartments in the mammalian brains and enhances
      IGF-1-induced ERK1/2 activation.
AB  - GIGYF2 has been reported as a candidate gene for PARK11-linked Parkinson's
      disease (PD). Heterozygous knockout of GIGYF2 results in neurodegeneration,
      suggesting important roles for GIGYF2 (Grb10 interacting GYF protein 2) in the
      CNS. In this study, we used novel GIGYF2 antibodies to clarify the distribution
      and function of GIGYF2. GIGYF2 was widely expressed, most highly in the pancreas
      and testis, and moderately in brain, lung, liver, kidney and spleen. In the
      brain, GIGYF2 was tightly associated with membrane in the S3 fraction, and
      localised in neuronal perikarya and proximal dendrites. Immunohistochemical
      analysis indicated sites of GIGYF2 localisation throughout the mouse brain, with
      high levels in the cerebral cortex, hippocampus, cerebellum, olfactory bulb and
      brainstem nuclei, but low levels in the substantia nigra and striatum. GIGYF2 was
      present in endosomes immunopositive for Rab4 and Grb10. Expression of GIGYF2
      altered insulin-like growth factor-1 (IGF-1) receptor trafficking and enhanced
      IGF-1-induced extracellular signal-regulated kinase 1/2 phosphorylation, but not
      IGF-1 receptor or serine/threonine protein kinase Akt phosphorylation. There were
      no significant differences in signalling activation between cells expressing wild
      type and putative PD-associated mutant GIGYF2. In PD brains, GIGYF2 did not
      localise to Lewy bodies. Our findings indicate a role for GIGYF2 in the
      regulation of signalling at endosomes, but no contribution of GIGYF2 to the
      pathogenesis of PD.

PMID- 20670376
TI  - Driving patterns of older adults: results from the Second Injury Control and Risk
      Survey.
AB  - OBJECTIVES: To describe older adults' driving patterns, including self-imposed
      driving restrictions and motor vehicle crashes (MVCs). DESIGN: The Second Injury
      Control and Risk Survey (ICARIS-2) was a national, random-digit-dial telephone
      survey conducted by the Centers for Disease Control and Prevention in 2001 to
      2003. ICARIS-2 sampled 113,476 English- and Spanish-speaking households, using
      weighting variables to generate national estimates. RESULTS: The response rate
      was 48% (N=9,684). Six percent (n=728) of respondents were aged 75 and older. Of
      these, 85.6% (n=613) were aged 75 to 84, and 14.4% (n=115) were aged 85 and
      older; 59.2% were female. Three-fourths (74.9%, 95% confidence interval (CI)=70.4
      79.4%) of adults aged 75 to 84 and 69.9% (95% CI=48.2-71.6%) aged 85 and older
      were current drivers. Most (81.9%; 95% CI=77.6-86.2%) older drivers limited their
      driving, usually in bad weather (59.0%), at night (57.0%), on long trips (49.6%),
      in traffic (49.0%), or at high speeds (33.6%); only 15.4% limited driving for
      medical reasons. Women were more likely to self-limit driving (odds ratio
      (OR)=1.83, 95% CI=0.99-3.39). Few (4.2%, 95% CI=2.4-6.1%) older adults reported
      MVC involvement in the past year as a driver or passenger. In multivariate
      analysis, drivers living alone (OR=3.93, 95% CI=1.55-9.95) and men (OR=2.59, 95%
      CI=1.18-5.67) were more likely to report a recent crash; drivers who self-limited
      were less likely (OR=0.55, 95% CI=0.18-1.60). CONCLUSION: Large majorities of
      older adults, including those aged 85 and older, are current drivers. Although
      many limit driving in hazardous conditions, fewer do for medical reasons. Men and
      older adults who live alone are more likely to report a recent MVC; those who
      self-limit their driving are less likely to report crash involvement.

PMID- 20670375
TI  - beta-Amyloid regulates leptin expression and tau phosphorylation through the
      mTORC1 signaling pathway.
AB  - High levels of the adipocytokine leptin are associated with reduced risk of
      Alzheimer's disease. Leptin treatment also reduces beta-amyloid (Abeta) levels in
      in vivo and in vitro models of Alzheimer's disease. Abeta and leptin interact
      with the Akt/mammalian target of rapamycin complex 1 (mTORC1) signaling pathway.
      Akt/mTORC1 activation reduces tau phosphorylation through the inhibition of the
      downstream enzyme GSK-3beta. mTORC1 also regulates translation of many proteins
      including leptin. While Abeta has been shown to inactivate Akt, inhibit mTORC1,
      and facilitate the phosphorylation of tau, leptin activates both Akt and mTORC1
      and reduces tau phosphorylation. However, the extent to which Abeta may modulate
      leptin expression and increase tau phosphorylation involving Akt/mTORC1 has not
      been determined. In this study, we show that incubation of organotypic slices
      from rabbit hippocampus with Abeta down-regulates leptin expression, inhibits
      Akt, activates GSK-3beta, increases tau phosphorylation, and inactivates mTORC1.
      Leptin treatment reverses Abeta effects by alleviating Akt inhibition, preventing
      GSK-3beta activation, reducing tau phosphorylation, and activating mTORC1. On the
      other hand, Rapamycin, an allosteric inhibitor of mTORC1, down-regulates leptin
      expression, increases tau phosphorylation, and does not affect Akt and GSK-3beta.
      Our results demonstrate for the first time that Abeta regulates leptin expression
      and tau phosphorylation through mTORC1.

PMID- 20670377
TI  - The effect of medication use on urinary incontinence in community-dwelling
      elderly women.
AB  - OBJECTIVES: To evaluate whether use of certain medications with potential
      urological effects is associated with development of incident urinary
      incontinence in community-resident older women. DESIGN: Longitudinal cohort
      study. SETTING: Pittsburgh, PA, and Memphis, TN. PARTICIPANTS: Nine hundred fifty
      nine healthy black and white women aged 65 and older enrolled in the Health,
      Aging and Body Composition Study without baseline (Year 1) self-reported urinary
      incontinence. MEASUREMENTS: Use of alpha blockers, anticholinergics, central
      nervous system medications (opioids, benzodiazepines, antidepressants,
      antipsychotics), diuretics (thiazide, loop, potassium sparing), and estrogen (all
      dosage forms) was determined during Year 3 interviews. Self-reported incident (>=
      weekly) incontinence in during the previous 12 months was assessed at Year 4
      interviews. RESULTS: Overall, 20.5% of these women reported incident incontinence
      at Year 4 (3 years from baseline). The most common medication used with potential
      urological activity was a thiazide diuretic (24.3%), followed by estrogen
      (22.2%); alpha blockers were the least commonly used (2.3%). Multivariable
      logistic regression analyses revealed that current users of alpha blockers
      (adjusted odds ratio (AOR)=4.98, 95% confidence interval (CI)=1.96-12.64) and
      estrogen (AOR=1.60, 95% CI=1.08-2.36) had a greater risk of urinary incontinence
      than nonusers. There was no greater risk (P>.05) of urinary incontinence with the
      current use of anticholinergics, central nervous system medications, or
      diuretics. No statistically significant race-by-medication use interactions were
      found (all P>.05). CONCLUSION: These results corroborate earlier reports that, in
      elderly women, use of alpha blockers or estrogens is associated with risk of self
      reported incident urinary incontinence.

PMID- 20670378
TI  - Effect of walking distance on 8-year incident depressive symptoms in elderly men
      with and without chronic disease: the Honolulu-Asia Aging Study.
AB  - OBJECTIVES: To determine the effect of walking on incident depressive symptoms in
      elderly Japanese-American men with and without chronic disease. DESIGN:
      Prospective cohort study. SETTING: The Honolulu-Asia Aging Study. PARTICIPANTS:
      Japanese-American men aged 71 to 93 at baseline. MEASUREMENTS: Physical activity
      was assessed according to self-reported distance walked per day. Depressive
      symptoms were measured using an 11-question version of the Centers for
      Epidemiologic Studies Depression Scale (CES-D 11) at the fourth examination
      (n=3,196) and at the seventh examination 8 years later (1999/00, n=1,417).
      Presence of incident depressive symptoms was defined as a CES-D 11 score of 9 or
      greater or taking antidepressants at Examination 7. Subjects with prevalent
      depressive symptoms at baseline were excluded. RESULTS: Age-adjusted 8-year
      incident depressive symptoms were 13.6%, 7.6%, and 8.5% for low (<0.25
      miles/day), intermediate (0.25-1.5 miles/day), and high (>1.5 miles/day) walking
      groups at baseline (P=0.008). Multiple logistic regression analyses, adjusted for
      age, education, marital status, cardiovascular risk factors, prevalent diseases,
      and functional impairment, showed that those in the intermediate and highest
      walking groups had significantly lower odds of developing 8-year incident
      depressive symptoms (odds ratio (OR)=0.52, 95% confidence interval (CI)=0.32
      0.83, P=.006 and OR=0.61, 95% CI= 0.39-0.97, P=.04, respectively). Analysis found
      that this association was significant only in participants without chronic
      diseases (coronary heart disease, cerebrovascular accident, cancer, Parkinson's
      disease, dementia, or cognitive impairment) at baseline. CONCLUSION: Daily
      physical activity (>=0.25 mile/day) is significantly associated with lower risk
      of 8-year incident depressive symptoms in elderly Japanese-American men without
      chronic disease at baseline.

PMID- 20670379
TI  - Waist circumference but not body mass index predicts long-term mortality in
      elderly subjects with chronic heart failure.
AB  - OBJECTIVES: To examine whether waist circumference (WC) and body-mass index (BMI)
      can predict long-term mortality in elderly subjects with and without chronic
      heart failure (CHF). DESIGN: Longitudinal evaluation with a 12-year follow-up.
      SETTING: Campania, a region of southern Italy. PARTICIPANTS: One thousand three
      hundred thirty-two subjects aged 65 and older selected from the electoral rolls
      of Campania. MEASUREMENTS: The relationship between WC or BMI and mortality
      during a 12-year follow-up in 125 subjects with and 1,143 subjects without CHF.
      RESULTS: Mortality increased as WC increased in elderly subjects without CHF
      (from 47.8% to 56.7%, P=.01), and the increase was even greater in patients with
      CHF (from 58.1% to 82.0%, P=.01). In contrast, mortality decreased as BMI
      increased in elderly subjects without CHF (from 53.8% to 46.1%, P0=.046) but not
      in those with CHF. According to Cox regression analysis, BMI protected against
      long-term mortality in the absence but not in the presence of CHF. In the absence
      of CHF, WC was associated with a 2% increased risk of long-term mortality for
      each 1-cm greater WC (Hazard Ratio (HR)=1.02, 95% confidence interval (CI)=1.01
      1.03; P<.001), versus 5% increased in the presence of CHF (HR=1.06, 95% CI=1.02
      1.10; P<.001). CONCLUSION: WC, but not BMI, is predictive of long-term mortality
      in elderly individuals with CHF and to a lesser extent in those without CHF.

PMID- 20670380
TI  - Neuroimaging in the clinical diagnosis of dementia: observations from a memory
      disorders clinic.
AB  - OBJECTIVES: To determine how often neuroimaging confirms, clarifies, or
      contradicts initial diagnoses of late-life cognitive disorders. DESIGN:
      Retrospective case review. SETTING: Outpatient clinic specializing in memory
      disorders. PARTICIPANTS: One hundred ninety-three consecutively referred
      cognitively impaired patients. MEASUREMENTS: Diagnoses using research criteria
      were developed for each patient at the first visit and ranged from cognitive
      impairment without dementia to dementias of single, complex, or indeterminate
      etiology. Structural (noncontrast magnetic resonance imaging) and perfusion
      (technetium-99m ethyl cysteine dimer single photon emission computed tomography)
      images were categorized together as normal, suggestive of specific diseases, or
      abnormal/not diagnostic. RESULTS: When a single neurodegenerative disease was
      suspected clinically (n=94), imaging confirmed the diagnosis in 50, contradicted
      the diagnosis in 32, and was abnormal/not diagnostic in 12. When more than one
      neurodegenerative etiology was clinically suspected (n=21), imaging assigned a
      single diagnosis in 13 and only cerebrovascular disease in one and was
      abnormal/not diagnostic in seven. In dementia not otherwise specified (NOS)
      (n=33), imaging suggested a specific etiology in 23 and was abnormal/not
      diagnostic in 10. Abnormal/not diagnostic images were more common in cognitive
      disorder NOS (n=25, 68%) than in other clinical groups (22%, chi-square=22.8
      P<.001). Neuroimaging indicators of cerebrovascular disease were common (60%
      prevalence) but not predicted by the presence of vascular risk factors alone.
      CONCLUSION: Overall, neuroimaging confirmed, clarified, or contradicted the
      initial clinical diagnosis in more than 80% of patients, whereas fewer than 20%
      had abnormal/not diagnostic patterns. Imaging suggested a complex dementia
      etiology in 21% of cases clinically thought to be caused by a single process,
      whereas 46% of complex clinical differential diagnoses appeared to reflect a
      single causal pattern. Further work is needed to determine whether refinement of
      clinical diagnoses using specialized neuroimaging improves clinical decision
      making and patient outcomes.

PMID- 20670381
TI  - Changing patterns in medication use with increasing probability of death for
      older Medicare beneficiaries.
AB  - OBJECTIVES: To determine whether use of symptom relief drugs (e.g.,
      antidepressants, anxiolytics, opioid analgesics, sleep aids) rises and use of two
      commonly prescribed classes of chronic medications (statins and osteoporosis
      drugs) falls with greater probability of death for older Medicare beneficiaries.
      DESIGN: Pooled cross-sectional study. SETTING: Noninstitutionalized older
      Medicare population in 2000 to 2005. PARTICIPANTS: Community-dwelling Medicare
      beneficiaries aged 65 and older (N=20,233). MEASUREMENTS: Use of medications
      measured according to dichotomous flags; intensity of use by annual medication
      fills. Annual probability of death modeled using logistic regression and
      stratified into seven groups with predicted probabilities of death that range
      from less than 5% to greater than 50%. Prevalence of use and intensity (mean
      prescription fills per month) were computed for each class of medication.
      RESULTS: For symptom relief medications, there is relatively constant use with
      increasing probability of death, along with greater intensity of use. For the two
      chronic medications, there was a monotonic decrease in use but at a relatively
      constant intensity. Decline in statin use ranged from 34.4% in the lowest
      mortality stratum to 17.6% for those in the highest (P<.001). Use of osteoporosis
      drugs fell from 10.4% to 6.6% over the same range (P<.001). CONCLUSION: Greater
      intensity of use of symptom relief medications with increasing probability of
      death is consistent with hypothesized use. The different profile for chronic
      medications suggests that the time to benefit is being considered regarding
      therapy initiation, which results in lower use.

PMID- 20670382
TI  - Nuclear transcription factors in mammalian mitochondria.
AB  - Nuclear transcription factors have been detected in mammalian mitochondria and
      may directly regulate mitochondrial gene expression. Emerging genomics techniques
      may overcome outstanding challenges in this field.

PMID- 20670383
TI  - Piecing together the problems in diagnosing low-level chromosomal mosaicism.
AB  - Low-level somatic chromosomal mosaicism, which usually arises from post-zygotic
      errors, is a known cause of several well defined genetic syndromes and has been
      implicated in various multifactorial diseases. It is, however, not easy to
      diagnose, as various physical and technical factors complicate its
      identification.

PMID- 20670384
TI  - Models of the human metabolic network: aiming to reconcile metabolomics and
      genomics.
AB  - The metabolic syndrome, inborn errors of metabolism, and drug-induced changes to
      metabolic states all bring about a seemingly bewildering array of alterations in
      metabolite concentrations; these often occur in tissues and cells that are
      distant from those containing the primary biochemical lesion. How is it possible
      to collect sufficient biochemical information from a patient to enable us to work
      backwards and pinpoint the primary lesion, and possibly treat it in this whole
      human metabolic network? Potential analyses have benefited from modern methods
      such as ultra-high-pressure liquid chromatography, mass spectrometry, nuclear
      magnetic resonance spectroscopy, and more. A yet greater challenge is the
      prediction of outcomes of possible modern therapies using drugs and genetic
      engineering. This exposes the notion of viewing metabolism from a completely
      different perspective, with focus on the enzymes, regulators, and structural
      elements that are encoded by genes that specify the amino acid sequences, and
      hence encode the various interactions, be they regulatory or catalytic. The
      mainstream view of metabolism is being challenged, so we discuss here the
      reconciling of traditionally quantitative chemocentric metabolism with the
      seemingly 'parameter-free' genomic description, and vice versa.

PMID- 20670385
TI  - Sepsis-related stress response: known knowns, known unknowns, and unknown
      unknowns.
AB  - The hypothalamic-pituitary-adrenal (HPA) axis response in sepsis remains to be
      elucidated. Apart from corticotropin-releasing hormone, adrenocorticotropic
      hormone, and cortisol, many other neuroendocrine factors participate in the
      regulation of HPA stress response. The HPA response to acute and chronic illness
      exerts a biphasic profile. Tissue corticosteroid resistance may also play an
      important role. All of these add to the complexity of the concept of 'relative
      adrenal insufficiency' and may account for the difficulty of clinical diagnosis
      and for the conflicting results of corticosteroid replacement therapy in severe
      sepsis/septic shock. The study by Lesur and colleagues expands our understanding
      of the mechanism, and further study of HPA stress response is warranted.

PMID- 20670386
TI  - Atrial fibrillation is not just an artefact in the ICU.
AB  - Atrial fibrillation (AF) is common in the intensive care unit (ICU) and is
      particularly frequent (46%) in septic shock patients. Inflammation favours AF in
      the general population, and there is a growing body of evidence that inflammation
      also plays a role in AF occurring after cardiac surgery but also in the general
      ICU. How such a finding could modify the therapeutic approach remains elusive.
      The impact of AF on mortality is not clearly demonstrated in the ICU, with AF
      reflecting essentially the severity of the underlying disease.

PMID- 20670387
TI  - Improving surgical outcomes: it is the destination not the journey.
AB  - Studies have demonstrated that optimising the circulating volume reduces
      morbidity after major surgery. This optimisation is usually achieved through
      maximisation of the stroke volume guided by oesophageal Doppler. New monitoring
      parameters of preload responsiveness using information from the arterial trace
      are now showing some promise in achieving the same goal. The present commentary
      examines these new parameters with respect to improving outcomes for the high
      risk surgical patient.

PMID- 20670388
TI  - Functional genomics and rheumatoid arthritis: where have we been and where should
      we go?
AB  - Studies in model organisms and humans have begun to reveal the complexity of the
      transcriptome. In addition to serving as passive templates from which genes are
      translated, RNA molecules are active, functional elements of the cell whose
      products can detect, interact with, and modify other transcripts. Gene expression
      profiling is the method most commonly used thus far to enrich our understanding
      of the molecular basis of rheumatoid arthritis in adults and juvenile idiopathic
      arthritis in children. The feasibility of this approach for patient
      classification (for example, active versus inactive disease, disease subsets) and
      improving prognosis (for example, response to therapy) has been demonstrated over
      the past 7 years. Mechanistic understanding of disease-related differences in
      gene expression must be interpreted in the context of interactions with
      transcriptional regulatory molecules and epigenetic alterations of the genome.
      Ongoing work regarding such functional complexities in the human genome will
      likely bring both insight and surprise to our understanding of rheumatoid
      arthritis.

PMID- 20670389
TI  - Hot times in the intensive care unit.
AB  - Fever is a common occurrence in the intensive care unit, and pharmacologic
      approaches are limited, particularly in patients unable to tolerate enteral
      medications. Although a study by Morris and colleagues in the previous issue of
      Critical Care suggests that intravenous ibuprofen is safe and effective in
      critically ill patients, the study is small and the drug was given over only a 24
      hour period. Additional studies will need to be performed to demonstrate the
      safety and efficacy of intravenous ibuprofen in critically ill patients.

PMID- 20670390
TI  - Assessment of monocytic HLA-DR expression in ICU patients: analytical issues for
      multicentric flow cytometry studies.

PMID- 20670391
TI  - The role for autopsy in the intensive care unit: technological considerations.

PMID- 20670392
TI  - Genomic information infrastructure after the deluge.
AB  - Maintaining up-to-date annotation on reference genomes is becoming more
      important, not less, as the ability to rapidly and cheaply resequence genomes
      expands.

PMID- 20670393
TI  - Controlling the direction of division.
AB  - Quyn and colleagues report that gut stem cells have a biased spindle orientation
      and asymmetric retention of label-retaining DNA. These features are lost in mouse
      and human tissues when the microtubule binding protein Apc is mutated. In the
      developing kidney, Apc acts downstream from primary cilium signaling to influence
      spindle orientation when noncanonical Wnt signaling predominates. Do gut stem
      cells also have primary cilia?

PMID- 20670394
TI  - The influence of genomics and proteomics on the development of potential vaccines
      against meningococcal infection.
AB  - There is a particular need for an effective vaccine against life-threatening
      meningitis and septicemia caused by Neisseria meningitidis (meningococcus)
      serogroup B strains. Vaccine strategies incorporating capsular polysaccharide
      have proved effective against other meningococcal serogroups, but are not
      applicable to serogroup B. Attention has therefore focused on the subcapsular
      outer membrane protein antigens as potential vaccine components. The sequencing
      of genomes from three serogroups and the availability of the corresponding
      translated protein databases, combined with the development of sensitive
      proteomic techniques, have opened up new avenues of meningococcal vaccine
      research. This has resulted in the identification of potential candidate antigens
      for incorporation into multicomponent meningococcal vaccines.

PMID- 20670395
TI  - The dilemma of good clinical practice in the study of compromised standards of
      care.
AB  - Four ethical issues loom over the study by Lieberman and colleagues--the absence
      of informed consent, the study being non-interventional in situations that
      typically call for life-saving interventions, the bias involved in doctors that
      study their own problematic practice and monopoly over intensive care unit
      triage, and ageism. We learn that the Israeli doctors in this study never make no
      treatment decisions regarding patients in need of mechanical ventilation. They
      are complicit with botched standards of care for these patients, however,
      accepting without much doubt an ethos of scarce resources and poor managerial
      habits. The main two practical lessons to be taken from this study are that, for
      patients in need of mechanical ventilation, compromised care is better than a
      policy of intubation only when the intensive care unit is available, and that
      vigorous efforts are needed in order to extirpate ageism.

PMID- 20670396
TI  - The Factors Influencing Depression Endpoints Research (FINDER) study: final
      results of Italian patients with depression.
AB  - BACKGROUND: Factors Influencing Depression Endpoints Research (FINDER) is a 6
      month, prospective, observational study carried out in 12 European countries
      aimed at investigating health-related quality of life (HRQoL) in outpatients
      receiving treatment for a first or new depressive episode. The Italian HRQoL data
      at 6 months is described in this report, and the factors associated with HRQoL
      changes were determined. METHODS: Data were collected at baseline, 3 and 6 months
      of treatment. HRQoL was measured using components of the 36-item Short Form
      Health Survey (SF-36; mental component summary (MCS), physical component summary
      (PCS)) and the European Quality of Life-5 Dimensions (EQ-5D; visual analogue
      scale (VAS) and health status index (HSI)). The Hospital Anxiety and Depression
      Scale (HADS) was adopted to evaluate depressive symptoms, while somatic and
      painful physical symptoms were assessed by using the 28-item Somatic Symptom
      Inventory (SSI-28) and a VAS. RESULTS: Of the initial 513 patients, 472 completed
      the 3-month observation and 466 the 6-month observation. The SF-36 and EQ-5D mean
      (+/- SD) scores showed HRQoL improvements at 3 months and a further smaller
      improvement at 6 months, with the most positive effects for SF-36 MCS (baseline
      22.0 +/- 9.2, 3 months 34.6 +/- 10.0; 6 months 39.3 +/- 9.5) and EQ-5D HSI
      (baseline 0.4 +/- 0.3; 3 months 0.7 +/- 0.3; 6 months 0.7 +/- 0.2). Depression
      and anxiety symptoms (HADS-D mean at baseline 13.3 +/- 4.2; HADS-A mean at
      baseline 12.2 +/- 3.9) consistently decreased during the first 3 months (8.7 +/-
      4.3; 7.5 +/- 3.6) and showed a further positive change at 6 months (6.9 +/- 4.3;
      5.8 +/- 3.4). Somatic and painful symptoms (SSI and VAS) significantly decreased,
      with the most positive changes in the SSI-28 somatic item (mean at baseline 2.4
      +/- 0.7; mean change at 3 months: -0.5; 95% CI -0.6 to -0.5; mean change at 6
      months: -0.7; 95% CI -0.8 to -0.7); in 'interference of overall pain with daily
      activities' (mean at baseline 45.2 +/- 30.7; mean change at 3 months -17.4; 95%
      CI -20.0 to -14.8; mean change at 6 months -24.4; 95% CI -27.3 to -21.6) and in
      'having pain while awake' (mean at baseline 41.1 +/- 29.0; mean change at 3
      months -13.7; 95% CI -15.9 to -11.5; mean change at 6 months -20.2; 95% CI -22.8
      to -17.5) domains. The results from linear regression analyses showed that the
      antidepressant switch within classes was consistently associated with a worsening
      in SF-36 MCS, EQ-5D VAS and HSI compared to non-switching treatment. Furthermore,
      between-group antidepressants (AD) switch was associated with a worse SF-36 MCS
      and EQ-5D HSI. MCS (P = 0.028), PCS (P = 0.036) and HSI (P = 0.002) were
      inversely related to the number of each previous additional depressive episode.
      PCS (P = 0.009) and HSI (P = 0.005) were also less improved in patients suffering
      from a chronic medical condition. Moreover, PCS (P = 0.044) and EQ-5D VAS (P <
      0.0001) worsening was consistently associated with the presence of a psychiatric
      illness in the 24 months before baseline. For every additional point on the SSI
      somatic score and on the overall pain VAS score at baseline, HSI score were on
      average 0.062 (P < 0.001) and 0.001 (P = 0.005) smaller, respectively.
      CONCLUSIONS: After starting AD treatment, HRQoL improvements at 3 and 6 months
      were observed. However, several factors can negatively influence HRQoL, such as
      the presence of somatic and painful symptoms, the presence of any chronic medical
      condition or previous psychiatric illness.

PMID- 20670397
TI  - Ultraviolet stress delays chromosome replication in light/dark synchronized cells
      of the marine cyanobacterium Prochlorococcus marinus PCC9511.
AB  - BACKGROUND: The marine cyanobacterium Prochlorococcus is very abundant in warm,
      nutrient-poor oceanic areas. The upper mixed layer of oceans is populated by high
      light-adapted Prochlorococcus ecotypes, which despite their tiny genome
      (approximately 1.7 Mb) seem to have developed efficient strategies to cope with
      stressful levels of photosynthetically active and ultraviolet (UV) radiation. At
      a molecular level, little is known yet about how such minimalist microorganisms
      manage to sustain high growth rates and avoid potentially detrimental, UV-induced
      mutations to their DNA. To address this question, we studied the cell cycle
      dynamics of P. marinus PCC9511 cells grown under high fluxes of visible light in
      the presence or absence of UV radiation. Near natural light-dark cycles of both
      light sources were obtained using a custom-designed illumination system
      (cyclostat). Expression patterns of key DNA synthesis and repair, cell division,
      and clock genes were analyzed in order to decipher molecular mechanisms of
      adaptation to UV radiation. RESULTS: The cell cycle of P. marinus PCC9511 was
      strongly synchronized by the day-night cycle. The most conspicuous response of
      cells to UV radiation was a delay in chromosome replication, with a peak of DNA
      synthesis shifted about 2 h into the dark period. This delay was seemingly linked
      to a strong downregulation of genes governing DNA replication (dnaA) and cell
      division (ftsZ, sepF), whereas most genes involved in DNA repair (such as recA,
      phrA, uvrA, ruvC, umuC) were already activated under high visible light and their
      expression levels were only slightly affected by additional UV exposure.
      CONCLUSIONS: Prochlorococcus cells modified the timing of the S phase in response
      to UV exposure, therefore reducing the risk that mutations would occur during
      this particularly sensitive stage of the cell cycle. We identified several
      possible explanations for the observed timeshift. Among these, the sharp decrease
      in transcript levels of the dnaA gene, encoding the DNA replication initiator
      protein, is sufficient by itself to explain this response, since DNA synthesis
      starts only when the cellular concentration of DnaA reaches a critical threshold.
      However, the observed response likely results from a more complex combination of
      UV-altered biological processes.

PMID- 20670398
TI  - When decisions of others matter to me: an electrophysiological analysis.
AB  - BACKGROUND: Actions of others may have immediate consequences for oneself. We
      probed the neural responses associated with the observation of another person's
      action using event-related potentials in a modified gambling task. In this task a
      "performer" bet either a higher or lower number and could win or lose this
      amount. Three different groups of "observers" were also studied. The first
      (neutral) group simply observed the performer's action, which had no consequences
      for the observers. In the second (parallel) group, wins/losses of the performer
      were paralleled by similar wins and losses by the observer. In the third
      (reverse) group, wins of the performer led to a loss of the observer and vice
      versa. RESULTS: ERPs of the performers showed a mediofrontal feedback related
      negativity (FRN) to losses. The neutral and parallel observer groups did
      similarly show an FRN response to the performer's losses with a topography
      indistinguishable from that seen in the performers. In the reverse group,
      however, the FRN occurred for wins of the performer which translated to losses
      for the observer. CONCLUSIONS: Taking into account previous experiments, we
      suggest that the FRN response in observers is driven by two evaluative processes
      (a) related to the benefit/loss for oneself and (b) related to the benefit/loss
      of another person.

PMID- 20670399
TI  - The prevalence of hepatitis B virus markers in a cohort of students in Bangui,
      Central African Republic.
AB  - BACKGROUND: Hepatitis B virus (HBV) is the major cause of chronic hepatitis,
      cirrhosis, and hepatocellular carcinoma. The global epidemiological scenario of
      HBV infection has been changing rapidly over the last two decades due to an
      effective immunization programme initiated by the World Health Organization. The
      objective of this study is to estimate the prevalence of HBV in apparently
      healthy young people and to identify the risk factors of transmission of the HBV
      among this population in Bangui. METHODS: Dried blood Spots from 801 adolescent
      high school and young adult university students were prepared by spotting a drop
      of whole blood (4 spots) from the same fingerprick onto Whatman filter paper. A
      blood sample aliquot eluted from DBS was then processed with commercial ELISA
      tests (Abbott Murex, Dartfort, UK) to detect HBsAg antigen, Anti-HBc and Anti-HBs
      antibodies). RESULTS: The overall prevalence was 42.3% for antibody to hepatitis
      B core antigen, 15.5% for HBsAg of which 1.3% of HBsAg alone. HBV familial
      antecedents, sexual activity and socioeconomic conditions were the main risk
      factors of HBV infection encountered in the adolescents and young adults.
      CONCLUSION: These results show for the first time the high prevalence of HBV in
      apparently healthy young people in Bangui. This high prevalence is age- and sex
      independent. Transmission risk factors were a familial antecedent of HBV, no
      utilisation of condoms and public scholarship. To lower HBV prevalence, an
      adequate program of active screening and vaccination for adolescents and young
      adults should be implemented, along with a universal immunization program.

PMID- 20670400
TI  - Hereditary hemochromatosis (HFE) genotypes in heart failure: relation to etiology
      and prognosis.
AB  - BACKGROUND: It is believed that hereditary hemochromatosis (HH) might play a role
      in cardiac disease (heart failure (HF) and ischemia). Mutations within several
      genes are HH-associated, the most common being the HFE gene. In a large cohort of
      HF patients, we sought to determine the etiological role and the prognostic
      significance of HFE genotypes. METHODS: We studied 667 HF patients (72.7% men)
      with depressed systolic function, enrolled in a multicentre trial with a follow
      up period of up to 5 years. All were genotyped for the known HFE variants C282Y,
      H63D and S65C. RESULTS: The genotype and allele frequencies in the HF group were
      similar to the frequencies determined in the general Danish population. In
      multivariable analysis mortality was not predicted by C282Y-carrier status (HR
      1.2, 95% CI: 0.8-1.7); H63D-carrier status (HR 1.0, 95% CI: 0.7-1.3); nor S65C
      carrier status (HR 1.2, 95% CI: 0.7-2.0). We identified 27 (4.1%) homozygous or
      compound heterozygous carriers of HFE variants. None of these carriers had a
      clinical presentation suggesting hemochromatosis, but hemoglobin and ferritin
      levels were higher than in the rest of the cohort. Furthermore, a trend towards
      reduced mortality was seen in this group in univariate analyses (HR 0.4, 95% CI:
      0.2-0.9, p = 0.03), but not in multivariate (HR 0.5, 95% CI: 0.2-1.2).
      CONCLUSION: HFE genotypes do not seem to be a significant contributor to the
      etiology of heart failure in Denmark. HFE variants do not affect mortality in HF.

PMID- 20670402
TI  - Increasing delivery of an outdoor journey intervention to people with stroke: A
      feasibility study involving five community rehabilitation teams.
AB  - BACKGROUND: Contrary to recommendations in a national clinical guideline,
      baseline audits from five community-based stroke rehabilitation teams
      demonstrated an evidence-practice gap; only 17% of eligible people with stroke
      were receiving targeted rehabilitation by occupational therapists and
      physiotherapists to increase outdoor journeys. The primary aim of this
      feasibility study was to design, test, and evaluate the impact of an
      implementation program intended to change the behaviour of community
      rehabilitation teams. A secondary aim was to measure the impact of this change on
      client outcomes. METHODS: A before-and-after study design was used. The primary
      data collection method was a medical record audit. Five community rehabilitation
      teams and a total of 12 professionals were recruited, including occupational
      therapists, physiotherapists, and a therapy assistant. A medical record audit was
      conducted twice over 12 months (total of 77 records pre-intervention, 53 records
      post-intervention) against a guideline recommendation about delivering outdoor
      journey sessions to people with stroke. A behavioural intervention (the 'Out-and
      About Implementation Program') was used to help change team practice. Active
      components of the intervention included feedback about the audit, barrier
      identification, and tailored education to target known barriers. The primary
      outcome measure was the proportion of medical records containing evidence of
      multiple outdoor journey sessions. Other outcomes of interest included the
      proportion of medical records that contained evidence of screening for outdoor
      journeys and driving by team members, and changes in patient outcomes. A small
      sample of community-dwelling people with stroke (n = 23) provided pre-post
      outcome data over three months. Data were analysed using descriptive statistics
      and t-tests. RESULTS: Medical record audits found that teams were delivering six
      or more outdoor journeys to 17% of people with stroke pre-intervention, rising to
      32% by 12 months post-intervention. This change represents a modest increase in
      practice behaviour (15%) across teams. More people with stroke (57%) reported
      getting out of the house as often as they wanted after receiving the outdoor
      journey intervention compared to 35% one year earlier; other quality of life
      outcomes also improved. CONCLUSIONS: The 'Out-and-About Implementation Program'
      helped rehabilitation teams to change their practice, implement evidence, and
      improve client outcomes. This behavioural intervention requires more rigorous
      evaluation using a cluster randomised trial design.

PMID- 20670401
TI  - Single-stranded heteroduplex intermediates in lambda Red homologous
      recombination.
AB  - BACKGROUND: The Red proteins of lambda phage mediate probably the simplest and
      most efficient homologous recombination reactions yet described. However the
      mechanism of dsDNA recombination remains undefined. RESULTS: Here we show that
      the Red proteins can act via full length single stranded intermediates to
      establish single stranded heteroduplexes at the replication fork. We created
      asymmetrically digestible dsDNA substrates by exploiting the fact that Redalpha
      exonuclease activity requires a 5' phosphorylated end, or is blocked by
      phosphothioates. Using these substrates, we found that the most efficient
      configuration for dsDNA recombination occurred when the strand that can prime
      Okazaki-like synthesis contained both homology regions on the same ssDNA
      molecule. Furthermore, we show that Red recombination requires replication of the
      target molecule. CONCLUSIONS: Hence we propose a new model for dsDNA
      recombination, termed 'beta' recombination, based on the formation of ssDNA
      heteroduplexes at the replication fork. Implications of the model were tested
      using (i) an in situ assay for recombination, which showed that recombination
      generated mixed wild type and recombinant colonies; and (ii) the predicted
      asymmetries of the homology arms, which showed that recombination is more
      sensitive to non-homologies attached to 5' than 3' ends. Whereas beta
      recombination can generate deletions in target BACs of at least 50 kb at about
      the same efficiency as small deletions, the converse event of insertion is very
      sensitive to increasing size. Insertions up to 3 kb are most efficiently achieved
      using beta recombination, however at greater sizes, an alternative Red-mediated
      mechanism(s) appears to be equally efficient. These findings define a new
      intermediate in homologous recombination, which also has practical implications
      for recombineering with the Red proteins.

PMID- 20670403
TI  - Association of bovine leptin polymorphisms with energy output and energy storage
      traits in progeny tested Holstein-Friesian dairy cattle sires.
AB  - BACKGROUND: Leptin modulates appetite, energy expenditure and the reproductive
      axis by signalling via its receptor the status of body energy stores to the
      brain. The present study aimed to quantify the associations between 10 novel and
      known single nucleotide polymorphisms in genes coding for leptin and leptin
      receptor with performance traits in 848 Holstein-Friesian sires, estimated from
      performance of up to 43,117 daughter-parity records per sire. RESULTS: All single
      nucleotide polymorphisms were segregating in this sample population and none
      deviated (P > 0.05) from Hardy-Weinberg equilibrium. Complete linkage
      disequilibrium existed between the novel polymorphism LEP-1609, and the
      previously identified polymorphisms LEP-1457 and LEP-580. LEP-2470 associated (P
      < 0.05) with milk protein concentration and calf perinatal mortality. It had a
      tendency to associate with milk yield (P < 0.1). The G allele of LEP-1238 was
      associated (P < 0.05) with reduced milk fat concentration, reduced milk protein
      concentration, longer gestation length and tended to associate (P < 0.1) with an
      increase in calving difficulty, calf perinatal mortality and somatic cells in the
      milk. LEP-963 exhibited an association (P < 0.05) with milk fat concentration,
      milk protein concentration, calving difficulty and gestation length. It also
      tended to associate with milk yield (P < 0.1). The R25C SNP associated (P < 0.05)
      with milk fat concentration, milk protein concentration, calving difficulty and
      length of gestation. The T allele of the Y7F SNP significantly associated with
      reduced angularity (P < 0.01) and reduced milk protein yield (P < 0.05). There
      was also a tendency (P < 0.1) for Y7F to associate with increased body condition
      score, reduced milk yield and shorter gestation (P < 0.1). A80V associated with
      reduced survival in the herd (P < 0.05). CONCLUSIONS: Several leptin
      polymorphisms (LEP-2470, LEP-1238, LEP-963, Y7F and R25C) associated with the
      energetically expensive process of lactogenesis. Only SNP Y7F associated with
      energy storage. Associations were also observed between leptin polymorphisms and
      calving difficulty, gestation length and calf perinatal mortality. The lack of an
      association between the leptin variants investigated with calving interval in
      this large data set would question the potential importance of these leptin
      variants, or indeed leptin, in selection for improved fertility in the Holstein
      Friesian dairy cow.

PMID- 20670404
TI  - Seasonal influences on sleep and executive function in the migratory White
      crowned Sparrow (Zonotrichia leucophrys gambelii).
AB  - BACKGROUND: We have previously shown that the White-crowned Sparrow (WCS)
      decreases sleep by 60% during a period of migratory restlessness relative to a
      non-migratory period when housed in a 12 h light: 12 h dark cycle. Despite this
      sleep reduction, accuracy of operant performance was not impaired, and in fact
      rates of responding were elevated during the migratory period, effects opposite
      to those routinely observed following enforced sleep deprivation. To determine
      whether the previously observed increases in operant responding were due to
      improved performance or to the effects of migration on activity level, here we
      assessed operant performance using a task in which optimal performance depends on
      the bird's ability to withhold a response for a fixed interval of time
      (differential-reinforcement-of-low-rate-behavior, or DRL); elevated response
      rates ultimately impair performance by decreasing access to food reward. To
      determine the influence of seasonal changes in day length on sleep and behavioral
      patterns, we recorded sleep and assessed operant performance across 4 distinct
      seasons (winter, spring, summer and fall) under a changing photoperiod. RESULTS:
      Sleep amount changed in response to photoperiod in winter and summer, with
      longest sleep duration in the winter. Sleep duration in the spring and fall
      migratory periods were similar to what we previously reported, and were
      comparable to sleep duration observed in summer. The most striking difference in
      sleep during the migratory periods compared to non-migratory periods was the
      change from discrete day-night temporal organization to an almost complete
      temporal fragmentation of sleep. The birds' ability to perform on the DRL task
      was significantly impaired during both migratory periods, but optimal performance
      was sustained during the two non-migratory periods. CONCLUSIONS: Birds showed
      dramatic changes in sleep duration across seasons, related to day length and
      migratory status. Migration was associated with changes in sleep amount and
      diurnal distribution pattern, whereas duration of sleep in the non-migratory
      periods was largely influenced by the light-dark cycle. Elevated response rates
      on the DRL task were observed during migration but not during the short sleep
      duration of summer, suggesting that the migratory periods may be associated with
      decreased inhibition/increased impulsivity. Although their daily sleep amounts
      and patterns may vary by season, birds are susceptible to sleep loss throughout
      the year, as evidenced by decreased responding rates following enforced sleep
      deprivation.

PMID- 20670405
TI  - MacroH2A subtypes contribute antagonistically to the transcriptional regulation
      of the ribosomal cistron during seasonal acclimatization of the carp fish.
AB  - BACKGROUND: Incorporation of histone variants into chromatin is one of the
      epigenetic mechanisms used for regulation of gene expression. Macro (m)H2A is a
      histone variant that has two different subtypes in vertebrates: mH2A1 and mH2A2.
      It is known that mH2A is associated with gene silencing, but recent studies
      indicate that these mH2A subtypes could contribute more widely to transcriptional
      regulation. We have previously demonstrated that the gene-reprogramming response
      mediates adaptation of the carp fish to its environment, and that ribosomal gene
      transcription is seasonally regulated in carp. However, there have been few
      studies investigating how epigenetic mechanisms contribute to environmental
      adaptation and, in particular, to ribosomal cistron regulation. RESULTS: In this
      paper, we report the occurrence of differential incorporation of mH2A subtypes
      into chromatin during seasonal adaptation in the carp, an event that concurs with
      opposing transcriptional states. Moreover, we observed that enrichment of mH2A1
      in the ribosomal cistron during winter, and conversely, enrichment of mH2A2
      during summer. mH2A1 consistently colocalizes with a heterochromatin marker
      (H3K27me2; histone H3 trimethylated at lysine 27) and mH2A2 with a euchromatin
      marker (H3K4me3; histone H3 trimethylated at lysine 4). Similar results were
      found for the L41gene, with enrichment of mH2A in the promoter region.
      CONCLUSIONS: We have characterized both mH2A subtypes from carp fish, and
      evaluated their participation in the regulation of the ribosomal cistron. Our
      findings indicate that differential incorporation of mH2A subtypes into the
      ribosome could regulate gene expression during the acclimatization process in
      carp. Our results reveal differential chromatin incorporation of the mH2A
      subtypes during the environmental adaptation process, correlating wtih
      antagonistic transcriptional states in the carp ribosomal cistron.

PMID- 20670406
TI  - Overexpression of hTERT increases stem-like properties and decreases spontaneous
      differentiation in human mesenchymal stem cell lines.
AB  - To overcome loss of stem-like properties and spontaneous differentiation those
      hinder the expansion and application of human mesenchymal stem cells (hMSCs), we
      have clonally isolated permanent and stable human MSC lines by ectopic
      overexpression of primary cell cultures of hMSCs with HPV 16 E6E7 and human
      telomerase reverse transcriptase (hTERT) genes. These cells were found to have a
      differentiation potential far beyond the ordinary hMSCs. They expressed
      trophoectoderm and germline specific markers upon differentiation with BMP4 and
      retinoic acid, respectively. Furthermore, they displayed higher osteogenic and
      neural differentiation efficiency than primary hMSCs or hMSCs expressed HPV16
      E6E7 alone with a decrease in methylation level as proven by a global CpG island
      methylation profile analysis. Notably, the demethylated CpG islands were highly
      associated with development and differentiation associated genes. Principal
      component analysis further pointed out the expression profile of the cells
      converged toward embryonic stem cells. These data demonstrate these cells not
      only are a useful tool for the studies of cell differentiation both for the
      mesenchymal and neurogenic lineages, but also provide a valuable source of cells
      for cell therapy studies in animal models of skeletal and neurological disorders.

PMID- 20670407
TI  - Neuronal transcription factor Brn-3a(l) is over expressed in high-grade ovarian
      carcinomas and tumor cells from ascites of patients with advanced-stage ovarian
      cancer.
AB  - OBJECTIVES: In view of the recent association of Brn-3 transcription factors with
      neuroblastomas, cervical, breast, and prostate cancers we examined the expression
      of Brn-3a(l) in normal ovaries and in different histological grades of ovarian
      tumors. The expression of Brn-3a(l) was also evaluated in normal ovarian and
      cancer cell lines and tumor cells isolated from the ascites of advanced-stage
      ovarian cancer patients. METHODS: Normal ovaries, benign, borderline, grades 1, 2
      and 3 ovarian tumors were analyzed by immunohistochemistry for Brn-3a(l)
      expression. A total of 46 ovarian specimens were included in the study.
      Immunofluorescence was used to investigate the expression of Brn-3a in normal
      ovarian and cancer cell lines. Brn-3a(l) expression was also evaluated by Western
      blot in tumor cells isolated from ascites of advanced-stage ovarian cancer
      patients and also in ovarian cancer cell lines. RESULTS: Nearly 12% of normal and
      benign ovarian tissues and 57% of borderline ovarian tumors were positive for
      epithelial Brn-3a(l) expression. Stromal staining was higher and it constituted
      40% of normal non-cancerous ovaries compared to 50 and 86% in benign and
      borderline tumors. On the other hand, 85-100% of grades 1, 2 & 3 ovarian tumors
      demonstrated nuclear and cytoplasmic Brn-3a(l) staining in the epithelium.
      Stromal staining in grades1, 2 and 3 tumors constituted 71-88% of total staining.
      Overall, immunoreactive Brn-3a was present in all grades of ovarian tumors. The
      extent of epithelial and stromal Brn-3a staining was significantly different
      between the normal and histological grades of tumors (epithelial-chi2 = 41.01, df
      = 20, P = 0.004, stromal-chi2 = 24.66. df = 15, P = 0.05). The extent of
      epithelial staining was significantly higher in grades 1 and 2 ovarian tumors
      compared to normal ovaries and benign ovarian tumors (p < 0.05). In parallel,
      stromal staining was significantly higher in grade 3 tumors compared to normal
      ovaries (p < 0.05). In addition, cytoplasmic and nuclear Brn-3a expression was
      evident in ovarian cancer cell lines while no such expression was observed in
      SV40 antigen immortalized normal ovarian cell lines. CONCLUSION: These data
      suggest that like other cancers, Brn-3a(l) expression is enhanced in ovarian
      tumors and its expression is consistent with its known role in inhibiting
      apoptosis and enhancing tumorigenesis. Specific targeting of Brn-3a may provide a
      useful strategy for regulating multiple tumor related genes involved with ovarian
      carcinomas.

PMID- 20670409
TI  - Community pharmacists' involvement in smoking cessation: familiarity and
      implementation of the National smoking cessation guideline in Finland.
AB  - BACKGROUND: Guidelines on smoking cessation (SC) emphasize healthcare cooperation
      and community pharmacists' involvement. This study explored the familiarity and
      implementation of the National SC Guideline in Finnish community pharmacies,
      factors relating to Guideline familiarity, implementation and provision of SC
      services. METHODS: A nationwide mail survey was sent to a systematic, sample of
      community pharmacy owners and staff pharmacists (total n = 2291). Response rate
      was 54% (n = 1190). Factors related to the SC Guideline familiarity were assessed
      by bivariate and multivariate analysis. RESULTS: Almost half (47%) of the
      respondents (n = 1190) were familiar with the SC Guideline and familiarity
      enhanced Guideline implementation. The familiarity was associated with the
      respondents' perceptions of their personal SC skills and knowledge (OR 3.8); of
      customers' value of counseling on nicotine replacement therapy (NRT) (OR 3.3);
      and regular use of a pocket card supporting SC counseling (OR 3.0). Pharmacists'
      workplaces' characteristics, such as size and geographical location were not
      associated with familiarity. In addition to recommending NRT, the pharmacists
      familiar with the Guideline used more frequently other Guideline-based SC
      methods, such as recommended non-pharmacological SC aids, compared to unfamiliar
      respondents. CONCLUSIONS: SC Guideline familiarity and implementation is crucial
      for community pharmacists' involvement in SC actions in addition to selling NRT
      products. Pharmacists can constitute a potential public health resource in SC
      easily accessible throughout the country.

PMID- 20670408
TI  - The impact of single versus mixed schistosome species infections on liver, spleen
      and bladder morbidity within Malian children pre- and post-praziquantel
      treatment.
AB  - BACKGROUND: In the developing world co-infections and polyparasitism within
      humans appear to be the rule rather than the exception, be it any combination of
      inter-specific and/or inter- and intra-Genera mixed infections. Mixed infections
      might generate synergistic or antagonistic interactions and thereby clinically
      affect individuals and/or impact parasite epidemiology. METHODS: The current
      study uniquely assesses both Schistosoma mansoni- and Schistosoma haematobium
      related morbidity of the liver and the bladder as assessed by ultrasound as well
      as spleen and liver morbidity through clinical exams. The impact of praziquantel
      (PZQ) treatment on such potential inter-specific schistosome interactions and
      resulting morbidity using uniquely detailed longitudinal data (pre- and one year
      post-PZQ treatment) arising from the National Schistosomiasis Control Program in
      three areas of Mali: Segou, Koulikoro and Bamako, is also evaluated. At baseline,
      data were collected from up to 2196 children (aged 7-14 years), 844 of which were
      infected with S. haematobium only, 124 with S. mansoni only and 477 with both.
      Follow-up data were collected from up to 1265 children. RESULTS: Results
      suggested lower liver morbidity in mixed compared to single S. mansoni infections
      and higher bladder morbidity in mixed compared to single S. haematobium
      infections. Single S. haematobium or S. mansoni infections were also associated
      with liver and spleen morbidity whilst only single S. haematobium infections were
      associated with bladder morbidity in these children (light S. haematobium
      infection OR: 4.3, p < 0.001 and heavy S. haematobium infection OR: 19, p <
      0.001). PZQ treatment contributed to the regression of some of the forms of such
      morbidities. CONCLUSIONS: Whilst the precise biological mechanisms for these
      observations remain to be ascertained, the results illustrate the importance of
      considering mixed species infections in any analyses of parasite-induced
      morbidity, including that for the proposed Disability Adjusted Life Years (DALYs)
      revised estimates of schistosomiasis morbidity.

PMID- 20670410
TI  - Bradykinin and adenosine receptors mediate desflurane induced postconditioning in
      human myocardium: role of reactive oxygen species.
AB  - BACKGROUND: Desflurane during early reperfusion has been shown to postcondition
      human myocardium, in vitro. We investigated the role of adenosine and bradykinin
      receptors, and generation of radical oxygen species in desflurane-induced
      postconditioning in human myocardium. METHODS: We recorded isometric contraction
      of human right atrial trabeculae hanged in an oxygenated Tyrode's solution (34
      degrees Celsius, stimulation frequency 1 Hz). After a 30-min hypoxic period,
      desflurane 6% was administered during the first 5 min of reoxygenation.
      Desflurane was administered alone or with pretreatment of N
      mercaptopropionylglycine, a reactive oxygen species scavenger, 8-(p
      Sulfophenyl)theophylline, an adenosine receptor antagonist, HOE140, a selective
      B2 bradykinin receptor antagonist. In separate groups, adenosine and bradykinin
      were administered during the first minutes of reoxygenation alone or in presence
      of N-mercaptopropionylglycine. The force of contraction of trabeculae was
      recorded continuously. Developed force at the end of a 60-min reoxygenation
      period was compared (mean +/- standard deviation) between the groups by a
      variance analysis and post hoc test. RESULTS: Desflurane 6% (84 +/- 6% of
      baseline) enhanced the recovery of force after 60-min of reoxygenation as
      compared to control group (51 +/- 8% of baseline, P < 0.0001). N
      mercaptopropionylglycine (54 +/- 3% of baseline), 8-(p-Sulfophenyl)theophylline
      (62 +/- 9% of baseline), HOE140 (58 +/- 6% of baseline) abolished desflurane
      induced postconditioning. Adenosine (80 +/- 9% of baseline) and bradykinin (83 +/
      4% of baseline) induced postconditioning (P < 0.0001 vs control), N
      mercaptopropionylglycine abolished the beneficial effects of adenosine and
      bradykinin (54 +/- 8 and 58 +/- 5% of baseline, respectively). CONCLUSIONS: In
      vitro, desflurane-induced postconditioning depends on reactive oxygen species
      production, activation of adenosine and bradykinin B2 receptors. And, the
      cardioprotective effect of adenosine and bradykinin administered at the beginning
      of reoxygenation, was mediated, at least in part, through ROS production.

PMID- 20670411
TI  - Bedside quantification of dead-space fraction using routine clinical data in
      patients with acute lung injury: secondary analysis of two prospective trials.
AB  - INTRODUCTION: Dead-space fraction (Vd/Vt) has been shown to be a powerful
      predictor of mortality in acute lung injury (ALI) patients. The measurement of
      Vd/Vt is based on the analysis of expired CO2 which is not a part of standard
      practice thus limiting widespread clinical application of this method. The
      objective of this study was to determine prognostic value of Vd/Vt estimated from
      routinely collected pulmonary variables. METHODS: Secondary analysis of the
      original data from two prospective studies of ALI patients. Estimated Vd/Vt was
      calculated using the rearranged alveolar gas equation: Vd/Vt=1
      [(0.86*VCO2est)/(VE*PaCO2)] where VCO2est is the estimated CO2 production
      calculated from the Harris Benedict equation, minute ventilation (VE) is obtained
      from the ventilator rate and expired tidal volume and PaCO2 from arterial gas
      analysis. Logistic regression models were created to determine the prognostic
      value of estimated Vd/Vt. RESULTS: One hundred and nine patients in Mayo Clinic
      validation cohort and 1896 patients in ARDS-net cohort demonstrated an increase
      in percent mortality for every 10% increase in Vd/Vt in a dose response fashion.
      After adjustment for non-pulmonary and pulmonary prognostic variables, both day 1
      (adjusted odds ratio-OR = 1.07, 95%CI 1.03 to 1.13) and day 3 (OR = 1.12, 95% CI
      1.06 to 1.18) estimated dead-space fraction predicted hospital mortality.
      CONCLUSIONS: Elevated estimated Vd/Vt predicts mortality in ALI patients in a
      dose response manner. A modified alveolar gas equation may be of clinical value
      for a rapid bedside estimation of Vd/Vt, utilizing routinely collected clinical
      data.

PMID- 20670412
TI  - Retailers' knowledge of tobacco harm reduction following the introduction of a
      new brand of smokeless tobacco.
AB  - BACKGROUND: Tobacco retailers are potential public health partners for tobacco
      harm reduction (THR). THR is the substitution of highly reduced-risk nicotine
      products, such as smokeless tobacco (ST) or pharmaceutical nicotine, for
      cigarettes. The introduction of a Swedish-style ST product, du Maurier snus (dMS)
      (Imperial Tobacco Canada Limited), which was marketed as a THR product, provided
      a unique opportunity to assess retailers' knowledge. This study examined
      retailers' knowledge of THR and compliance with recommendations regarding tobacco
      sales to young adults. METHODS: Male researchers, who may have looked younger
      than 18 years old, visited 60 stores in Edmonton that sold dMS. The researchers
      asked the retailers questions about dMS and its health risks relative to those
      from other tobacco products. They also attempted to purchase dMS to ascertain
      whether retailers would ask for identification to verify that they were at least
      18 years old. RESULTS: Overall, the retailers were only moderately knowledgeable
      about THR and the differences between dMS and other tobacco products. About half
      of the retailers correctly indicated that snus is safer than cigarettes; half of
      whom knew it is safer because it is smoke-free. Fifty percent incorrectly
      believed that snus causes oral cancer. Less than fifty percent indicated that dMS
      differs from chewing tobacco because it is in pouches and is used without
      spitting or chewing (making it more promising for THR). Most (90%) of the
      retailers asked the researchers for identification when selling dMS. CONCLUSION:
      Tobacco retailers are potentially important sources of information about THR,
      particularly since there are restrictions on the promotion of all tobacco
      products (regardless of the actual health risks) in Canada. This study found that
      many retailers in Edmonton do not know the relative health risks of different
      tobacco products and are therefore unable to pass on accurate information to
      smokers.

PMID- 20670413
TI  - Meditation acutely improves psychomotor vigilance, and may decrease sleep need.
AB  - BACKGROUND: A number of benefits from meditation have been claimed by those who
      practice various traditions, but few have been well tested in scientifically
      controlled studies. Among these claims are improved performance and decreased
      sleep need. Therefore, in these studies we assess whether meditation leads to an
      immediate performance improvement on a well validated psychomotor vigilance task
      (PVT), and second, whether longer bouts of meditation may alter sleep need.
      METHODS: The primary study assessed PVT reaction times before and after 40 minute
      periods of mediation, nap, or a control activity using a within subject cross
      over design. This study utilized novice meditators who were current university
      students (n = 10). Novice meditators completed 40 minutes of meditation, nap, or
      control activities on six different days (two separate days for each condition),
      plus one night of total sleep deprivation on a different night, followed by 40
      minutes of meditation.A second study examined sleep times in long term
      experienced meditators (n = 7) vs. non-meditators (n = 23). Experienced
      meditators and controls were age and sex matched and living in the Delhi region
      of India at the time of the study. Both groups continued their normal activities
      while monitoring their sleep and meditation times. RESULTS: Novice meditators
      were tested on the PVT before each activity, 10 minutes after each activity and
      one hour later. All ten novice meditators improved their PVT reaction times
      immediately following periods of meditation, and all but one got worse
      immediately following naps. Sleep deprivation produced a slower baseline reaction
      time (RT) on the PVT that still improved significantly following a period of
      meditation. In experiments with long-term experienced meditators, sleep duration
      was measured using both sleep journals and actigraphy. Sleep duration in these
      subjects was lower than control non-meditators and general population norms, with
      no apparent decrements in PVT scores. CONCLUSIONS: These results suggest that
      meditation provides at least a short-term performance improvement even in novice
      meditators. In long term meditators, multiple hours spent in meditation are
      associated with a significant decrease in total sleep time when compared with age
      and sex matched controls who did not meditate. Whether meditation can actually
      replace a portion of sleep or pay-off sleep debt is under further investigation.

PMID- 20670414
TI  - Further decrease in glycated hemoglobin following ingestion of a LoBAG30 diet for
      10 weeks compared to 5 weeks in people with untreated type 2 diabetes.
AB  - BACKGROUND: We previously determined that a weight-maintenance, non-ketogenic
      diet containing 30% carbohydrate (CHO), 30% protein, 40% fat, (30:30:40)
      (LoBAG30) decreased glycated hemoglobin (%tGHb) from 10.8 to 9.1% over a 5 week
      period in subjects with untreated type 2 diabetes. Both the fasting glucose and
      postprandial glucose area were decreased. Our objective in the present 10-week
      study was to determine: 1) whether the above results could be maintained, or even
      improved (suggesting a metabolic adaptation) and 2) whether the subjects would
      accept the diet for this longer time period. In addition, protein balance, and a
      number of other blood and urine constituents were quantified at 5 and at 10 weeks
      on the LoBAG30 diet to address metabolic adaptation. METHODS: Eight men with
      untreated type 2 diabetes were studied over a 10-week period. Blood was drawn and
      urine was collected over a 24 hour period at the beginning of the study with
      subjects ingesting a standard diet of 55% CHO, 15% protein, 30% fat, and at the
      end of 5 and 10 weeks following ingestion of a LoBAG30 diet. RESULTS: Body weight
      was stable. Fasting glucose decreased by 19% at week 5 and 28% at week 10; 24-h
      total glucose area decreased by 27% at week 5 and 35% at week 10 compared to
      baseline. Insulin did not change. Mean %tGHb decreased by 13% at week 5, 25% at
      week 10, and was still decreasing linearly, indicating that a metabolic
      adaptation occurred. Serum NEFA, AAN, uric acid, urea, albumin, prealbumin, TSH,
      Total T3, free T4, B12, folate, homocysteine, creatinine, growth hormone and
      renin did not differ between weeks 5 and 10. IGF-1 increased modestly. Urinary
      glucose decreased; urinary pH and calcium were similar. CONCLUSIONS: A LoBAG30
      diet resulted in continued improvement in glycemic control. This improvement
      occurred without significant weight loss, with unchanged insulin and glucagon
      profiles, and without deterioration in serum lipids, blood pressure or kidney
      function. Extending the duration of time on a LoBAG30 diet from 5 to 10 weeks had
      little or no further effect on the hormones and metabolites measured, i.e. a
      metabolic equilibrium was established.

PMID- 20670415
TI  - Strong reproductive barriers in a narrow hybrid zone of West-Mediterranean green
      toads (Bufo viridis subgroup) with Plio-Pleistocene divergence.
AB  - BACKGROUND: One key question in evolutionary biology deals with the mode and rate
      at which reproductive isolation accumulates during allopatric speciation. Little
      is known about secondary contacts of recently diverged anuran species. Here we
      conduct a multi-locus field study to investigate a contact zone between two
      lineages of green toads with an estimated divergence time of 2.7 My, and report
      results from preliminary experimental crosses. RESULTS: The Sicilian endemic Bufo
      siculus and the Italian mainland-origin B. balearicus form a narrow hybrid zone
      east of Mt. Etna. Despite bidirectional mtDNA introgression over a ca. 40 km
      North-South cline, no F1 hybrids could be found, and nuclear genomes display
      almost no admixture. Populations from each side of the contact zone showed
      depressed genetic diversity and very strong differentiation (FST = 0.52).
      Preliminary experimental crosses point to a slightly reduced fitness in F1
      hybrids, a strong hybrid breakdown in backcrossed offspring (F1 x parental, with
      very few reaching metamorphosis) and a complete and early mortality in F2 (F1 x
      F1). CONCLUSION: Genetic patterns at the contact zone are molded by drift and
      selection. Local effective sizes are reduced by the geography and history of the
      contact zone, B. balearicus populations being at the front wave of a recent
      expansion (late Pleistocene). Selection against hybrids likely results from
      intrinsic genomic causes (disruption of coadapted sets of genes in backcrosses
      and F2-hybrids), possibly reinforced by local adaptation (the ranges of the two
      taxa roughly coincide with the borders of semiarid and arid climates). The
      absence of F1 in the field might be due to premating isolation mechanisms. Our
      results, show that these lineages have evolved almost complete reproductive
      isolation after some 2.7 My of divergence, contrasting sharply with evidence from
      laboratory experiments that some anuran species may still produce viable F1
      offspring after > 20 My of divergence.

PMID- 20670416
TI  - Clustering of dystonia in some pedigrees with autosomal dominant essential tremor
      suggests the existence of a distinct subtype of essential tremor.
AB  - BACKGROUND: There is an ongoing debate whether essential tremor (ET) represents a
      monosymptomatic disorder or other neurologic symptoms are compatible with the
      diagnosis of ET. Many patients with clinically definite ET develop dystonia. It
      remains unknown whether tremor associated with dystonia represent a subtype of
      ET. We hypothesized that ET with dystonia represents a distinct subtype of ET.
      METHODS: We studied patients diagnosed with familial ET and dystonia. We included
      only those patients whose first-degree relatives met diagnostic criteria for ET
      or dystonia with tremor. This cohort was ascertained for the presence of focal,
      segmental, multifocal, hemidystonia or generalized dystonia, and ET. RESULTS: We
      included 463 patients from 97 kindreds with autosomal dominant mode of
      inheritance (AD), defined by the vertical transmission of the disease. ET was the
      predominant phenotype in every ascertained family and each was phenotypically
      classified as AD ET. "Pure" ET was present in 365 individuals. Focal or segmental
      dystonia was present in 98 of the 463 patients; 87 of the 98 patients had ET
      associated with dystonia, one had dystonic tremor and ten had isolated dystonia.
      The age of onset and tremor severity did not differ between patients with "pure"
      ET and ET associated with dystonia. We did not observe a random distribution of
      dystonia in AD ET pedigrees and all patients with dystonia associated with ET
      were clustered in 28% of all included pedigrees (27/97, p < 0.001). CONCLUSIONS:
      Our results suggest that familial ET associated with dystonia may represent a
      distinct subtype of ET.

PMID- 20670417
TI  - A quantitative approach to study indirect effects among disease proteins in the
      human protein interaction network.
AB  - BACKGROUND: Systems biology makes it possible to study larger and more intricate
      systems than before, so it is now possible to look at the molecular basis of
      several diseases in parallel. Analyzing the interaction network of proteins in
      the cell can be the key to understand how complex processes lead to diseases.
      Novel tools in network analysis provide the possibility to quantify the key
      interacting proteins in large networks as well as proteins that connect them.
      Here we suggest a new method to study the relationships between topology and
      functionality of the protein-protein interaction network, by identifying key
      mediator proteins possibly maintaining indirect relationships among proteins
      causing various diseases. RESULTS: Based on the i2d and OMIM databases, we have
      constructed (i) a network of proteins causing five selected diseases (DP, disease
      proteins) plus their interacting partners (IP, non-disease proteins), the DPIP
      network and (ii) a protein network showing only these IPs and their interactions,
      the IP network. The five investigated diseases were (1) various cancers, (2)
      heart diseases, (3) obesity, (4) diabetes and (5) autism. We have quantified the
      number and strength of IP-mediated indirect effects between the five groups of
      disease proteins and hypothetically identified the most important mediator
      proteins linking heart disease to obesity or diabetes in the IP network. The
      results present the relationship between mediator role and centrality, as well as
      between mediator role and functional properties of these proteins. CONCLUSIONS:
      We show that a protein which plays an important indirect mediator role between
      two diseases is not necessarily a hub in the PPI network. This may suggest that,
      even if hub proteins and disease proteins are trivially of great interest,
      mediators may also deserve more attention, especially if disease-disease
      associations are to be understood. Identifying the hubs may not be sufficient to
      understand particular pathways. We have found that the mediators between heart
      diseases and obesity, as well as heart diseases and diabetes are of relatively
      high functional importance in the cell. The mediator proteins suggested here
      should be experimentally tested as products of hypothetical disease-related
      proteins.

PMID- 20670418
TI  - Health need and the use of alternative medicine among adults who do not use
      conventional medicine.
AB  - BACKGROUND: We hypothesize that a substantial portion of individuals who forgo
      conventional care in a given year turn to some form of alternative medicine. This
      study also examines whether individuals who use only alternative medicine will
      differ substantially in health and sociodemographic status from individuals using
      neither alternative medicine nor conventional care in a given year. To identify
      those factors that predict alternative medicine use in those not using
      conventional care, we employed the socio-behavioral model of healthcare
      utilization. METHODS: The current study is a cross-sectional regression analysis
      using data from the 2002 National Health Interview Survey. Data were collected in
      person from 31,044 adults throughout the 50 states and the District of Columbia.
      RESULTS: 19.3% of adults (38.3 million) did not use conventional care in a 12
      month period, although 39.5% of these individuals (14.7 million) reported having
      one or more problems with their health. Of those not using conventional care,
      24.8% (9.5 million) used alternative medicine. Users of alternative medicine had
      more health needs and were more likely to delay conventional care because of both
      cost and non-cost factors compared to those not using alternative medicine. While
      individual predisposing factors (gender, education) were positively associated
      with alternative medicine use, enabling factors (poverty status, insurance
      coverage) were not. CONCLUSIONS: We found that a quarter of individuals who forgo
      conventional care in a given year turn towards alternative medicine. Our study
      suggests that the potential determinants of using only alternative medicine are
      multifactorial. Future research is needed to examine the decision process behind
      an individual's choice to use alternative medicine but not conventional medicine
      and the clinical outcomes of this choice.

PMID- 20670419
TI  - Confirmation of a low HER2 positivity rate of breast carcinomas - limitations of
      immunohistochemistry and in situ hybridization.
AB  - BACKGROUND: Accurate assessment of the human epidermal growth factor receptor 2
      (HER2) of invasive breast cancer is essential to treatment decisions since the
      advent of targeted therapy with the humanized monoclonal antibody trastuzumab and
      the dual tyrosine kinase inhibitor lapatinib. In the literature, the percentage
      of HER2-overexpressed/amplified breast carcinomas range from 3% to 30%. The
      routinely assigned low rate of 9% of HER2-overexpressed breast carcinomas alarmed
      one of our gynecologists who requested to confirm our HER2 test results. METHODS:
      A small study of 83 patients with breast carcinoma was designed to reexamine the
      routinely assessed HER2 status using immunohistochemistry and fluorescence in
      situ hybridization. RESULTS: The low rate of 9% of HER2-overexpressed/amplified
      breast tumors (DIN1C-3, invasive carcinoma) could be confirmed. However, FISH
      revealed two false positive cases and one false negative case. Moreover a case
      with an equivocal result in FISH was detected. CONCLUSION: The HER2 positivity
      rate may be as low as 9%. The novel ASCO/CAP criteria for assessing
      immunohistochemical results in HER 2 testing reduce the false positive rate of
      HER2. First-line testing with immunohistochemistry may obscure false positive and
      false negative test results. In heterogeneous carcinomas even fluorescence in
      situ hybridization may not succeed in a correct evaluation of HER2.

PMID- 20670420
TI  - Adaptive robot training for the treatment of incoordination in Multiple
      Sclerosis.
AB  - BACKGROUND: Cerebellar symptoms are extremely disabling and are common in
      Multiple Sclerosis (MS) subjects. In this feasibility study, we developed and
      tested a robot therapy protocol, aimed at the rehabilitation of incoordination in
      MS subjects. METHODS: Eight subjects with clinically defined MS performed planar
      reaching movements while grasping the handle of a robotic manipulandum, which
      generated forces that either reduced (error-reducing, ER) or enhanced (error
      enhancing, EE) the curvature of their movements, assessed at the beginning of
      each session. The protocol was designed to adapt to the individual subjects'
      impairments, as well as to improvements between sessions (if any). Each subject
      went through a total of eight training sessions. To compare the effect of the two
      variants of the training protocol (ER and EE), we used a cross-over design
      consisting of two blocks of sessions (four ER and four EE; 2 sessions/week),
      separated by a 2-weeks rest period. The order of application of ER and EE
      exercises was randomized across subjects. The primary outcome measure was the
      modification of the Nine Hole Peg Test (NHPT) score. Other clinical scales and
      movement kinematics were taken as secondary outcomes. RESULTS: Most subjects
      revealed a preserved ability to adapt to the robot-generated forces. No
      significant differences were observed in EE and ER training. However over
      sessions, subjects exhibited an average 24% decrease in their NHPT score. The
      other clinical scales showed small improvements for at least some of the
      subjects. After training, movements became smoother, and their curvature
      decreased significantly over sessions. CONCLUSIONS: The results point to an
      improved coordination over sessions and suggest a potential benefit of a short
      term, customized, and adaptive robot therapy for MS subjects.

PMID- 20670421
TI  - Focused nurse-defibrillation training: a simple and cost-effective strategy to
      improve survival from in-hospital cardiac arrest.
AB  - Time to first defibrillation is widely accepted to correlate closely with
      survival and recovery of neurological function after cardiac arrest due to
      ventricular fibrillation or ventricular tachycardia. Focused training of a cadre
      of nurses to defibrillate on their own initiative may significantly decrease time
      to first defibrillation in cases of in-hospital cardiac arrest outside of
      critical care units. Such a program may be the best single strategy to improve in
      hospital survival, simply and at reasonable cost.

PMID- 20670422
TI  - Quantitative comparison of lipoprotein fractions derived from human plasma and
      serum by liquid chromatography-tandem mass spectrometry.
AB  - BACKGROUND: Lipoproteins are complex, globular molecules which play essential
      roles in the transport and metabolism of cholesterol. Their implication in the
      development of cardiovascular diseases, such as atherosclerosis, has sustained a
      great deal of interest in these particles. Their various functions, and their
      contribution to the development of atherosclerosis, are often attributed to their
      protein constituents, which vary greatly among the different lipoprotein classes.
      Recent advances in the field of mass spectrometry have provided insight into the
      array of proteins associated with low-density lipoproteins (LDLs) and, even more
      so, with high-density lipoproteins (HDLs). Plasma and serum are the most commonly
      used samples for the analysis of lipoproteins. Although these lipoprotein sources
      are unique, it was our goal to determine whether or not their inherent
      differences would ultimately affect a quantitative analysis of the LDL and HDL
      proteomes. To this end, we isolated LDL and HDL fractions with fast protein
      liquid chromatography-size exclusion chromatography (FPLC-SEC) from both human
      plasma and serum samples from the same individuals. After delipidating these
      samples, we performed a quantitative proteomic analysis to compare the
      lipoprotein-associated proteins derived from both plasma and serum. RESULTS:
      Although the primary differences between the samples are found in fibrinogen
      proteins which are removed from serum, it of interest to note that, with respect
      to LDL-associated proteins, apolipoproteinB-100 was found at significantly higher
      levels in serum samples. Complement component 3 was found at significantly higher
      levels in serum-derived HDL fractions. Both of these proteins are known LDL- and
      HDL-associated proteins, respectively. CONCLUSION: Overall, the results from our
      study indicate that both plasma and serum samples are equally suited for
      proteomic studies, and provide similar results. These findings are particularly
      important for studies profiling proteomic differences in lipoprotein particle
      composition in a variety of disease conditions, including cardiovascular disease.

PMID- 20670423
TI  - Using direct observations on multiple occasions to measure household food
      availability among low-income Mexicano residents in Texas colonias.
AB  - BACKGROUND: It has been recognized that the availability of foods in the home are
      important to nutritional health, and may influence the dietary behavior of
      children, adolescents, and adults. It is therefore important to understand food
      choices in the context of the household setting. Considering their importance,
      the measurement of household food resources becomes critical.Because most studies
      use a single point of data collection to determine the types of foods that are
      present in the home, which can miss the change in availability within a month and
      when resources are not available, the primary objective of this pilot study was
      to examine the feasibility and value of conducting weekly in-home assessments of
      household food resources over the course of one month among low-income Mexicano
      families in Texas colonias. METHODS: We conducted five in-home household food
      inventories over a thirty-day period in a small convenience sample; determined
      the frequency that food items were present in the participating households; and
      compared a one-time measurement with multiple measurements.After the development
      and pre-testing of the 252-item culturally and linguistically- appropriate
      household food inventory instrument that used direct observation to determine the
      presence and amount of food and beverage items in the home (refrigerator,
      freezer, pantry, elsewhere), two trained promotoras recruited a convenience
      sample of 6 households; administered a baseline questionnaire (personal info,
      shopping habits, and food security); conducted 5 in-home assessments (7-day
      interval) over a 30-day period; and documented grocery shopping and other food
      related activities within the previous week of each in-home assessment. All data
      were collected in Spanish. Descriptive statistics were calculated for mean and
      frequency of sample characteristics, food-related activities, food security, and
      the presence of individual food items. Due to the small sample size of the pilot
      data, the Friedman Test and Kendall's W were used to assess the consistency of
      household food supplies across multiple observations. RESULTS: Complete data were
      collected from all 6 Mexicano women (33.2y +/- 3.3; 6.5 +/- 1.5 adults/children
      in household (HH); 5 HH received weekly income; and all were food insecure. All
      households purchased groceries within a week of at least four of the five
      assessments. The weekly presence and amounts of fresh and processed fruits and
      vegetables, dairy, meats, breads, cereals, beverages, and oils and fats varied.
      Further, the results revealed the inadequacy of a one-time measurement of
      household food resources, compared with multiple measures. The first household
      food inventory as a one-time measure would have mistakenly identified at least
      one-half of the participant households without fresh fruit, canned vegetables,
      dairy, protein foods, grains, chips, and sugar-sweetened beverages. CONCLUSIONS:
      This study highlights the value of documenting weekly household food supplies,
      especially in households where income resources may be more volatile. Clearly,
      the data show that a single HFI may miss the changes in availability--presence
      and amount--that occur among low-income Mexicano households who face challenges
      that require frequent purchase of foods and beverages. Use of multiple household
      food inventories can inform the development and implementation of nutrition
      related policies and culturally sensitive nutrition education programs.

PMID- 20670424
TI  - Early administration of norepinephrine increases cardiac preload and cardiac
      output in septic patients with life-threatening hypotension.
AB  - INTRODUCTION: We sought to examine the cardiac consequences of early
      administration of norepinephrine in severely hypotensive sepsis patients
      hospitalized in a medical intensive care unit of a university hospital. METHODS:
      We included 105 septic-shock patients who already had received volume
      resuscitation. All received norepinephrine early because of life-threatening
      hypotension and the need to achieve a sufficient perfusion pressure rapidly and
      to maintain adequate flow. We analyzed the changes in transpulmonary
      thermodilution variables associated with the increase in mean arterial pressure
      (MAP) induced by norepinephrine when the achieved MAP was >=65 mm Hg. RESULTS:
      Norepinephrine significantly increased MAP from 54 +/- 8 to 76 +/- 9 mm Hg,
      cardiac index (CI) from 3.2 +/- 1.0 to 3.6 +/- 1.1 L/min/m2, stroke volume index
      (SVI) from 34 +/- 12 to 39 +/- 13 ml/m2, global end-diastolic volume index
      (GEDVI) from 694 +/- 148 to 742 +/- 168 ml/m2, and cardiac function index (CFI)
      from 4.7 +/- 1.5 to 5.0 +/- 1.6 per min. Beneficial hemodynamic effects on CI,
      SVI, GEDVI, and CFI were observed in the group of 71 patients with a baseline
      echocardiographic left ventricular ejection fraction (LVEF) >45%, as well as in
      the group of 34 patients with a baseline LVEF <=45%. No change in CI, SVI, GEDVI,
      or CFI was observed in the 17 patients with baseline LVEF <=45% for whom values
      of MAP >=75 mm Hg were achieved with norepinephrine. CONCLUSIONS: Early
      administration of norepinephrine aimed at rapidly achieving a sufficient
      perfusion pressure in severely hypotensive septic-shock patients is able to
      increase cardiac output through an increase in cardiac preload and cardiac
      contractility. This effect remained in patients with poor cardiac contractility
      except when values of MAP >=75 mm Hg were achieved.

PMID- 20670425
TI  - Joint modeling of multivariate longitudinal data and the dropout process in a
      competing risk setting: application to ICU data.
AB  - BACKGROUND: Joint modeling of longitudinal and survival data has been
      increasingly considered in clinical trials, notably in cancer and AIDS. In
      critically ill patients admitted to an intensive care unit (ICU), such models
      also appear to be of interest in the investigation of the effect of treatment on
      severity scores due to the likely association between the longitudinal score and
      the dropout process, either caused by deaths or live discharges from the ICU.
      However, in this competing risk setting, only cause-specific hazard sub-models
      for the multiple failure types data have been used. METHODS: We propose a joint
      model that consists of a linear mixed effects submodel for the longitudinal
      outcome, and a proportional subdistribution hazards submodel for the competing
      risks survival data, linked together by latent random effects. We use Markov
      chain Monte Carlo technique of Gibbs sampling to estimate the joint posterior
      distribution of the unknown parameters of the model. The proposed method is
      studied and compared to joint model with cause-specific hazards submodel in
      simulations and applied to a data set that consisted of repeated measurements of
      severity score and time of discharge and death for 1,401 ICU patients. RESULTS:
      Time by treatment interaction was observed on the evolution of the mean SOFA
      score when ignoring potentially informative dropouts due to ICU deaths and live
      discharges from the ICU. In contrast, this was no longer significant when
      modeling the cause-specific hazards of informative dropouts. Such a time by
      treatment interaction persisted together with an evidence of treatment effect on
      the hazard of death when modeling dropout processes through the use of the Fine
      and Gray model for sub-distribution hazards. CONCLUSIONS: In the joint modeling
      of competing risks with longitudinal response, differences in the handling of
      competing risk outcomes appear to translate into the estimated difference in
      treatment effect on the longitudinal outcome. Such a modeling strategy should be
      carefully defined prior to analysis.

PMID- 20670426
TI  - Struma ovarii associated with pseudo-Meigs' syndrome and elevated serum CA 125: a
      case report and review of the literature.
AB  - The association of pseudo-Meigs' syndrome, elevation of CA 125 to the struma
      ovarii is a rare condition. So far only nine cases have been reported in English
      literature through MEDLINE search. Here we report a 46-year-old case of the
      struma ovarii, presented with ascites, hydrothorax, right ovarian mass and
      elevated serum CA 125 level. These findings were misdiagnosed for an ovarian
      malignancy at the first impression. Immediate resolution of the ascites,
      hydrothorax and normalization of the serum CA 125 level were followed by ovarian
      mass removal. Struma ovarii could be a rare cause of ascites, hydrothorax,
      ovarian mass and elevated CA 125. This rare condition should be considered in the
      differential diagnosis in patents with ascites and pleural effusions but with
      negative cytology.

PMID- 20670427
TI  - Expression and activation of the oxytocin receptor in airway smooth muscle cells:
      Regulation by TNFalpha and IL-13.
AB  - BACKGROUND: During pregnancy asthma may remain stable, improve or worsen. The
      factors underlying the deleterious effect of pregnancy on asthma remain unknown.
      Oxytocin is a neurohypophyseal protein that regulates a number of central and
      peripheral responses such as uterine contractions and milk ejection. Additional
      evidence suggests that oxytocin regulates inflammatory processes in other tissues
      given the ubiquitous expression of the oxytocin receptor. The purpose of this
      study was to define the role of oxytocin in modulating human airway smooth muscle
      (HASMCs) function in the presence and absence of IL-13 and TNFalpha, cytokines
      known to be important in asthma. METHOD: Expression of oxytocin receptor in
      cultured HASMCs was performed by real time PCR and flow cytomery assays.
      Responses to oxytocin was assessed by fluorimetry to detect calcium signals while
      isolated tracheal rings and precision cut lung slices (PCLS) were used to measure
      contractile responses. Finally, ELISA was used to compare oxytocin levels in the
      bronchoalveloar lavage (BAL) samples from healthy subjects and those with asthma.
      RESULTS: PCR analysis demonstrates that OXTR is expressed in HASMCs under basal
      conditions and that both interleukin (IL)-13 and tumor necrosis factor (TNFalpha)
      stimulate a time-dependent increase in OXTR expression at 6 and 18 hr.
      Additionally, oxytocin increases cytosolic calcium levels in fura-2-loaded HASMCs
      that were enhanced in cells treated for 24 hr with IL-13. Interestingly, TNFalpha
      had little effect on oxytocin-induced calcium response despite increasing
      receptor expression. Using isolated murine tracheal rings and PCLS, oxytocin also
      promoted force generation and airway narrowing. Further, oxytocin levels are
      detectable in bronchoalveolar lavage (BAL) fluid derived from healthy subjects as
      well as from those with asthma. CONCLUSION: Taken together, we show that
      cytokines modulate the expression of functional oxytocin receptors in HASMCs
      suggesting a potential role for inflammation-induced changes in oxytocin receptor
      signaling in the regulation of airway hyper-responsiveness in asthma.

PMID- 20670428
TI  - The relationship between staff skill mix, costs and outcomes in intermediate care
      services.
AB  - BACKGROUND: The purpose of this study was to assess the relationship between
      skill mix, patient outcomes, length of stay and service costs in older peoples'
      intermediate care services in England. METHODS: We undertook multivariate
      analysis of data collected as part of the National Evaluation of Intermediate
      Care Services. Data were analysed on between 337 and 403 older people admitted to
      14 different intermediate care teams. Independent variables were the numbers of
      different types of staff within a team and the ratio of support staff to
      professionally qualified staff within teams. Outcome measures include the Barthel
      index, EQ-5D, length of service provision and costs of care. RESULTS: Increased
      skill mix (raising the number of different types of staff by one) is associated
      with a 17% reduction in service costs (p = 0.011). There is weak evidence (p =
      0.090) that a higher ratio of support staff to qualified staff leads to greater
      improvements in EQ-5D scores of patients. CONCLUSIONS: This study provides
      limited evidence on the relationship between multidisciplinary skill mix and
      outcomes in intermediate care services.

PMID- 20670429
TI  - Glycyrrhizic acid improved lipoprotein lipase expression, insulin sensitivity,
      serum lipid and lipid deposition in high-fat diet-induced obese rats.
AB  - BACKGROUND: The metabolic syndrome, known also as the insulin resistance
      syndrome, refers to the clustering of several risk factors for atherosclerotic
      cardiovascular disease. Dyslipidaemia is a hallmark of the syndrome and is
      associated with a whole body reduction in the activity of lipoprotein lipase
      (LPL), an enzyme under the regulation of the class of nuclear receptors known as
      peroxisome proliferator-activated receptor (PPAR). Glycyrrhizic acid (GA), a
      triterpenoid saponin, is the primary bioactive constituent of the roots of the
      shrub Glycyrrhiza glabra. Studies have indicated that triterpenoids could act as
      PPAR agonists and GA is therefore postulated to restore LPL expression in the
      insulin resistant state. RESULTS: Oral administration of 100 mg/kg of GA to high
      fat diet-induced obese rats for 28 days led to significant reduction in blood
      glucose concentration and improvement in insulin sensitivity as indicated by the
      homeostasis model assessment of insulin resistance (HOMA-IR) (p < 0.05). LPL
      expression was up-regulated in the kidney, heart, quadriceps femoris, abdominal
      muscle and the visceral and subcutaneous adipose tissues but down-regulated in
      the liver--a condition in reverse to that seen in high-fat diet-induced obese
      rats without GA. With regard to lipid metabolism, GA administration led to
      significant hypotriglyceridemic and HDL-raising effects (p < 0.05), with a
      consistent reduction in serum free fatty acid, total cholesterol and LDL
      cholesterol and significant decrease in tissue lipid deposition across all
      studied tissue (p < 0.01). CONCLUSION: In conclusion, GA may be a potential
      compound in improving dyslipidaemia by selectively inducing LPL expression in non
      hepatic tissues. Such up-regulation was accompanied by a GA-mediated improvement
      in insulin sensitivity, which may be associated with a decrease in tissue lipid
      deposition. The HDL-raising effect of GA suggests the antiatherosclerotic
      properties of GA.

PMID- 20670430
TI  - Analysis of adenovirus trans-complementation-mediated gene expression controlled
      by melanoma-specific TETP promoter in vitro.
AB  - BACKGROUND: Human adenoviruses (Ads) have substantial potential for clinical
      applications in cancer patients. Conditionally replicating adenoviruses (CRAds)
      include oncolytic adenoviruses in which expression of the immediate early viral
      transactivator protein E1A is controlled by a cancer cell-selective promoter. To
      enhance efficacy, CRAds are further armed to contain therapeutic genes. Due to
      size constraints of the capsid geometry, the capacity for packaging transgenes
      into Ads is, however, limited. To overcome this limitation, the employment of E1A
      deleted replication-deficient viruses carrying therapeutic genes in combination
      with replication-competent CRAd vectors expressing E1A in trans has been
      proposed. Most trans-complementing studies involved transgene expressions from
      strong ubiquitous promoters, and thereby relied entirely on the cancer cell
      specificity of the CRAd vector. RESULTS: Here we tested the trans-complementation
      of a CRAd and a replication-deficient transgene vector containing the same cancer
      cell-selective promoter. Hereto, we generated two new vectors expressing IL-2 and
      CD40L from a bicistronic expression cassette under the control of the
      melanoma/melanocyte-specific tyrosinase enhancer tyrosinase promoter (TETP),
      which we previously described for the melanoma-specific CRAd vector AdDeltaEP
      TETP. These vectors gave rise to tightly controlled melanoma-specific transgene
      expression levels, which were only 5 to 40-fold lower than those from vectors
      controlled by the nonselective CMV promoter. Reporter analyses using Ad-CMV-eGFP
      in combination with AdDeltaEP-TETP revealed a high level of trans-complementation
      in melanoma cells (up to about 30-fold), but not in non-melanoma cells, unlike
      the AdCMV-eGFP/wtAd5 binary vector system, which was equally efficient in
      melanoma and non-melanoma cells. Similar findings were obtained when replacing
      the transgene vector AdCMV-eGFP with AdCMV-IL-2 or AdCMV-CD40L. However, the
      combination of the novel AdTETP-CD40L/IL-2 vector with AdDeltaEP-TETP or wtAd5
      gave reproducible moderate 3-fold enhancements of IL-2 by trans-complementation
      only. CONCLUSIONS: The cancer cell-selective TETP tested here did not give the
      expected enforceable transgene expression typically achieved in the Ad trans
      complementing system. Reasons for this could include virus-mediated down
      regulation of limiting transcription factors, and/or competition for such factors
      by different promoters. Whether this finding is unique to the particular promoter
      system tested here, or also occurs with other promoters warrants further
      investigations.

PMID- 20670431
TI  - Regional variations in and correlates of disability-free life expectancy among
      older adults in China.
AB  - BACKGROUND: Considerable socioeconomic and health inequalities have been reported
      in China. However, because of a lack of appropriate data, limited research has
      been conducted on variations in disability-free life expectancy (DFLE) among
      older adults. This study aimed to use the most up-to-date disability survey data
      to explore geographical variations in DFLE at age 60 in China and to identify the
      socioeconomic and health care factors that partially account for these
      variations. METHODS: This study used 2006 mortality data extrapolated from the
      1990 and 2000 Census and disability data from a national disability survey
      conducted in 2006. Disability was performance based and was diagnosed by trained
      physicians. DFLE was calculated by region using the Sullivan method. Multiple
      linear regression models by gender were conducted to explore correlates of DFLE.
      RESULTS: DFLE at age 60 varied widely by region, from 11.2 to 20.8 years in 2006.
      Per capita gross domestic product, proportion of urban residents, and access to
      health care were the primary factors associated with geographical variations in
      DFLE. CONCLUSION: The pattern of differences in DFLE by region mirrors the
      pattern of regional economic development in China. Countermeasures to decrease
      regional differences in DFLE include accelerating regional economic development
      and improving health care distribution.

PMID- 20670432
TI  - KeaA, a Dictyostelium Kelch-domain protein that regulates the response to stress
      and development.
AB  - BACKGROUND: The protein kinase YakA is responsible for the growth arrest and
      induction of developmental processes that occur upon starvation of Dictyostelium
      cells. yakA- cells are aggregation deficient, have a faster cell cycle and are
      hypersensitive to oxidative and nitrosoative stress. With the aim of isolating
      members of the YakA pathway, suppressors of the death induced by nitrosoative
      stress in the yakA- cells were identified. One of the suppressor mutations
      occurred in keaA, a gene identical to DG1106 and similar to Keap1 from mice and
      the Kelch protein from Drosophila, among others that contain Kelch domains.
      RESULTS: A mutation in keaA suppresses the hypersensitivity to oxidative and
      nitrosoative stresses but not the faster growth phenotype of yakA- cells. The
      growth profile of keaA deficient cells indicates that this gene is necessary for
      growth. keaA deficient cells are more resistant to nitrosoative and oxidative
      stress and keaA is necessary for the production and detection of cAMP. A
      morphological analysis of keaA deficient cells during multicellular development
      indicated that, although the mutant is not absolutely deficient in aggregation,
      cells do not efficiently participate in the process. Gene expression analysis
      using cDNA microarrays of wild-type and keaA deficient cells indicated a role for
      KeaA in the regulation of the cell cycle and pre-starvation responses.
      CONCLUSIONS: KeaA is required for cAMP signaling following stress. Our studies
      indicate a role for kelch proteins in the signaling that regulates the cell cycle
      and development in response to changes in the environmental conditions.

PMID- 20670433
TI  - Primary pigmented nodular adrenocortical disease presenting with a unilateral
      adrenocortical nodule treated with bilateral laparoscopic adrenalectomy: a case
      report.
AB  - INTRODUCTION: Primary pigmented nodular adrenocortical disease is a rare cause of
      adrenocorticotropic hormone-independent Cushing's syndrome. We report an uncommon
      primary pigmented nodular adrenocortical disease case presenting with a
      unilateral adrenocortical nodule and provide a brief overview of the existing
      literature. CASE PRESENTATION: A 27-year-old Caucasian woman was admitted to our
      Department with adrenocorticotropic hormone-independent Cushing's syndrome. Its
      cause was initially considered a left adrenocortical adenoma based on computer
      tomography imaging. The patient underwent left laparoscopic adrenalectomy and
      histological examination revealed pigmented micronodular adrenal hyperplasia.
      Evaluation for the presence of Carney complex was negative. Six months later
      recurrence of hypercortisolism was documented and a right laparoscopic
      adrenalectomy was performed further establishing the diagnosis of primary
      pigmented nodular adrenocortical disease. After a nine-year follow-up there is no
      evidence of residual disease. CONCLUSIONS: Even though primary pigmented nodular
      adrenocortical disease is a rare cause of Cushing's syndrome, it should be
      included in the differential diagnosis of adrenocorticotropic hormone-independent
      Cushing's syndrome, especially because adrenal imaging can be misleading
      mimicking other adrenocortical diseases. Bilateral laparoscopic adrenalectomy is
      the preferred treatment in these subjects.

PMID- 20670434
TI  - Multiple domains in the Crumbs Homolog 2a (Crb2a) protein are required for
      regulating rod photoreceptor size.
AB  - BACKGROUND: Vertebrate retinal photoreceptors are morphologically complex cells
      that have two apical regions, the inner segment and the outer segment. The outer
      segment is a modified cilium and is continuously regenerated throughout life. The
      molecular and cellular mechanisms that underlie vertebrate photoreceptor
      morphogenesis and the maintenance of the outer segment are largely unknown. The
      Crumbs (Crb) complex is a key regulator of apical membrane identity and size in
      epithelia and in Drosophila photoreceptors. Mutations in the human gene CRUMBS
      HOMOLOG 1 (CRB1) are associated with early and severe vision loss. Drosophila
      Crumbs and vertebrate Crb1 and Crumbs homolog 2 (Crb2) proteins are structurally
      similar, all are single pass transmembrane proteins with a large extracellular
      domain containing multiple laminin- and EGF-like repeats and a small
      intracellular domain containing a FERM-binding domain and a PDZ-binding domain.
      In order to begin to understand the role of the Crb family of proteins in
      vertebrate photoreceptors we generated stable transgenic zebrafish in which rod
      photoreceptors overexpress full-length Crb2a protein and several other Crb2a
      constructs engineered to lack specific domains. RESULTS: We examined the
      localization of Crb2a constructs and their effects on rod morphology. We found
      that only the full-length Crb2a protein approximated the normal localization of
      Crb2a protein apical to adherens junctions in the photoreceptor inner segment.
      Several Crb2a construct proteins localized abnormally to the outer segment and
      one construct localized abnormally to the cell body. Overexpression of full
      length Crb2a greatly increased inner segment size while expression of several
      other constructs increased outer segment size. CONCLUSIONS: Our observations
      suggest that particular domains in Crb2a regulate its localization and thus may
      regulate its regionalized function. Our results also suggest that the PDZ-binding
      domain in Crb2a might bring a protein(s) into the Crb complex that alters the
      function of the FERM-binding domain.

PMID- 20670435
TI  - Acquired hemophilia as the cause of life-threatening hemorrhage in a 94-year-old
      man: a case report.
AB  - INTRODUCTION: Acquired factor VIII deficiency is a rare entity that can lead to
      severe and life-threatening bleeding. We describe a case of severe bleeding from
      the tongue secondary to acquired hemophilia and discuss treatment options,
      including aminocaproic acid and recombinant factor VIII, which have not been
      widely reported in the literature for the management of such patients. CASE
      PRESENTATION: A 94-year-old Caucasian man presented to our institution with
      diffuse bruising and extensive bleeding from the tongue secondary to mechanical
      trauma. He had no prior history of bleeding and his medical history was
      unremarkable except for dementia and hypertension. Coagulation studies revealed a
      prolonged activated partial thromboplastin time and a mixing study was consistent
      with the presence of an inhibitor. Quantitative assays revealed a reduced level
      of factor VIII activity (1%) and the presence of a factor VIII inhibitor,
      measured at seven Bethesda units, in the serum. Oral prednisone therapy
      (60mg/day) was given. He also received intravenous aminocaproic acid and human
      concentrate of factor VIII (Humate-P) and topical anti-thrombolytic agents (100
      units of topical thrombin cream). His hospital course was prolonged because of
      persistent bleeding and the development of profuse melena. He required eight
      units of packed red blood cells for transfusion. Hospitalization was also
      complicated by bradycardia of unclear etiology, which started after infusion of
      aminocaproic acid. His activated partial thromboplastin time gradually
      normalized. He was discharged to a rehabilitation facility three weeks later with
      improving symptoms, stable hematocrit and resolving bruises. CONCLUSIONS:
      Clinicians should suspect a diagnosis of acquired hemophilia in older patients
      with unexplained persistent and profound bleeding from uncommon soft tissues,
      including the tongue. Use of factor VIII (Humate-P) and aminocaproic acid can be
      useful in this coagulopathy but clinicians should be aware of possible life
      threatening side effects in older patients, including bradycardia.

PMID- 20670436
TI  - Clock genes and their genomic distributions in three species of salmonid fishes:
      Associations with genes regulating sexual maturation and cell cycling.
AB  - BACKGROUND: Clock family genes encode transcription factors that regulate clock
      controlled genes and thus regulate many physiological mechanisms/processes in a
      circadian fashion. Clock1 duplicates and copies of Clock3 and NPAS2-like genes
      were partially characterized (genomic sequencing) and mapped using family-based
      indels/SNPs in rainbow trout (RT)(Oncorhynchus mykiss), Arctic charr
      (AC)(Salvelinus alpinus), and Atlantic salmon (AS)(Salmo salar) mapping panels.
      RESULTS: Clock1 duplicates mapped to linkage groups RT-8/-24, AC-16/-13 and AS-2/
      18. Clock3/NPAS2-like genes mapped to RT-9/-20, AC-20/-43, and AS-5. Most of
      these linkage group regions containing the Clock gene duplicates were derived
      from the most recent 4R whole genome duplication event specific to the salmonids.
      These linkage groups contain quantitative trait loci (QTL) for life history and
      growth traits (i.e., reproduction and cell cycling). Comparative synteny analyses
      with other model teleost species reveal a high degree of conservation for genes
      in these chromosomal regions suggesting that functionally related or co-regulated
      genes are clustered in syntenic blocks. For example, anti-mullerian hormone
      (amh), regulating sexual maturation, and ornithine decarboxylase antizymes (oaz1
      and oaz2), regulating cell cycling, are contained within these syntenic blocks.
      CONCLUSIONS: Synteny analyses indicate that regions homologous to major life
      history QTL regions in salmonids contain many candidate genes that are likely to
      influence reproduction and cell cycling. The order of these genes is highly
      conserved across the vertebrate species examined, and as such, these genes may
      make up a functional cluster of genes that are likely co-regulated. CLOCK, as a
      transcription factor, is found within this block and therefore has the potential
      to cis-regulate the processes influenced by these genes. Additionally, clock
      controlled genes (CCGs) are located in other life-history QTL regions within
      salmonids suggesting that at least in part, trans-regulation of these QTL regions
      may also occur via Clock expression.

PMID- 20670438
TI  - Randomised controlled trial of local corticosteroid injections for carpal tunnel
      syndrome in general practice.
AB  - BACKGROUND: Carpal tunnel syndrome is caused by entrapment of the median nerve
      and results in pain, tingling and numbness in the wrist and hand. It is a common
      condition in general practice. Effectiveness of treatment by intracarpal
      corticosteroid injection has never been investigated in general practice. The
      objective of this study was to determine if corticosteroid injections for carpal
      tunnel syndrome provided by general practitioners are effective. METHODS: In this
      study 69 participants with a clinical diagnosis of carpal tunnel syndrome were
      recruited from 20 general practices. Short-term outcomes were assessed in a
      randomised, placebo-controlled trial. Long-term results were assessed in a
      prospective cohort-study of steroid responders. Participants were randomised to
      intracarpal injections of 1 ml triamcinolonacetonide 10 mg/ml (TCA) or 1 ml NaCl
      (placebo). Non-responders to NaCl were treated with additional TCA injections.
      Main outcomes were immediate treatment success, mean score of the Symptom
      Severity Scale (SSS) and Functional Status Scale (FSS) of the Boston carpal
      tunnel questionnaire, subjective improvement and proportion of participants with
      recurrences during follow-up. Duration of follow-up was twelve months. RESULTS:
      The TCA-group (36 participants) had better outcomes than the NaCl-group (33
      participants) during short-term assessment for outcome measures treatment
      response, mean improvement of SSS-score (the mean difference in change score was
      0.637 {95% CI: 0.320, 0.960; p < 0.001}) and FSS-score (the mean difference in
      change score was 0.588 {95% CI: 0.232, 0.944; p = 0.002}) and perceived
      improvement (p = 0.01). The number to treat to achieve satisfactory partial
      treatment response or complete resolution of symptoms and signs was 3 (95%
      CI:1.83, 9.72).49% of TCA-responders (17/35) had recurrences during follow-up. In
      the group of TCA-responders without recurrences (51%, 18/35) outcomes for SSS
      score and FSS-score deteriorated during the follow-up period of 12 months (resp.
      p = 0.008 and p = 0.012). CONCLUSIONS: Corticosteroid injections for CTS provided
      by general practitioners are effective regarding short-term outcomes when
      compared to placebo injections. The short-term beneficial treatment effects of
      steroid injections deteriorated during the follow-up period of twelve months and
      half of the cohort of steroid-responders had recurrences. TRIAL REGISTRATION:
      Current Controlled Trials ISRCTN53171398.

PMID- 20670437
TI  - Personalized therapies in the cancer "omics" era.
AB  - A molecular hallmark of cancer is the presence of genetic alterations in the
      tumoral DNA. Understanding how these alterations translate into the malignant
      phenotype is critical for the adequate treatment of oncologic diseases. Several
      cancer genome sequencing reports have uncovered the number and identity of
      proteins and pathways frequently altered in cancer. In this article we discuss
      how integration of these genomic data with other biological and proteomic studies
      may help in designing anticancer therapies "a la carte". An important conclusion
      is that next generation treatment of neoplasias must be based on rational drug
      combinations that target various pathways and cellular entities that sustain the
      survival of cancer cells.

PMID- 20670439
TI  - The usefulness of a clinical 'scorecard' in managing patients with sore throat in
      general practice.
AB  - BACKGROUND:  OBJECTIVE: To evaluate the usefulness of a clinical scorecard in
      managing sore throat in general practice. DESIGN: Validation study of scorecard
      for sore throat with a throat swab culture used as the 'gold standard'. SETTING:
      A solo family practice in rural New South Wales, AustraliaParticipants: Patients
      attending with sore throat. METHODS: Patients from the age of 5 years and above
      presenting with the main symptom of a sore throat, and who have not had any
      antibiotic treatment in the previous two weeks, were invited to participate in
      the study. The doctor completed a scorecard for each patient participating and
      took a throat swab for culture. Adult patients (> 16 yrs) were asked to complete
      a patient satisfaction questionnaire, while guardians accompanying children (5 yr
      to < 16 yrs old) were asked to complete a similar, guardian questionnaire. MAIN
      OUTCOME MEASURES: 1. Ability of a new scorecard to differentiate between
      bacterial and non-bacterial sore throat.2. Patients' trust in the scorecard.
      RESULTS: The scorecard has a sensitivity of 93.33%, a specificity of 63.16%, a
      positive predictive value of 50% and a negative predictive value of 96%. The
      sensitivity is better than other sore throat scorecards that have been published
      but with a slightly lower specificity.There was a high level of patient trust in
      the scorecard was (85.8% agreement). Patients also trusted their doctor's
      judgement based on the scorecard (90.6% agreement). CONCLUSIONS: As the scorecard
      has a high sensitivity but only a moderate specificity, this means that it is
      more reliable for negative results, i.e. when the result suggests a viral
      infection. When the result favours a bacterial sore throat, then a high
      sensitivity can mean that there are a number of false positives. GPs can be
      confident in withholding antibiotics when the scorecard indicates a viral
      infection.

PMID- 20670440
TI  - The incidence of total hip arthroplasty after hip arthroscopy in osteoarthritic
      patients.
AB  - OBJECTIVE: To assess the incidence of total hip arthroplasty (THA) in
      osteoarthritic patients who were treated by arthroscopic debridement and to
      evaluate factors that might influence the time interval from the first hip
      arthroscopy to THA. DESIGN: Retrospective clinical series METHODS: Follow-up data
      and surgical reports were retrieved from 564 records of osteoarthritic patients
      that have had hip arthroscopy between the years 2002 to 2009 with a mean follow
      up time of 3.2 years (range, 1-6.4 years). The time interval between the first
      hip arthroscopy to THA was modelled as a function of patient age; level of
      cartilage damage; procedures performed and repeated arthroscopies with the use of
      multivariate regression analysis. RESULTS: Ninety (16%) of all participants
      eventually required THA. The awaiting time from the first arthroscopy to a hip
      replacement was found to be longer in patients younger than 55 years and in a
      milder osteoarthritic stage. Patients that experienced repeated hip scopes had a
      longer time to THA than those with only a single procedure. Procedures performed
      concomitant with debridement and lavage did not affect the time interval to THA.
      CONCLUSIONS: In our series of arthroscopic treatment of hip osteoarthritis, 16%
      required THA over a period of 7 years. Factors that influence the time to
      arthroplasty were age, degree of osteoarthritis and recurrent procedures.

PMID- 20670441
TI  - Structure-function relationships of wheat flavone O-methyltransferase: Homology
      modeling and site-directed mutagenesis.
AB  - BACKGROUND: Wheat (Triticum aestivum L.) O-methyltransferase (TaOMT2) catalyzes
      the sequential methylation of the flavone, tricetin, to its 3'-methyl- (selgin),
      3',5'-dimethyl- (tricin) and 3',4',5'-trimethyl ether derivatives. Tricin, a
      potential multifunctional nutraceutical, is the major enzyme reaction product.
      These successive methylations raised the question as to whether they take place
      in one, or different active sites. We constructed a 3-D model of this protein
      using the crystal structure of the highly homologous Medicago sativa caffeic
      acid/5-hydroxyferulic acid O-methyltransferase (MsCOMT) as a template with the
      aim of proposing a mechanism for multiple methyl transfer reactions in wheat.
      RESULTS: This model revealed unique structural features of TaOMT2 which permit
      the stepwise methylation of tricetin. Substrate binding is mediated by an
      extensive network of H-bonds and van der Waals interactions. Mutational analysis
      of structurally guided active site residues identified those involved in binding
      and catalysis. The partly buried tricetin active site, as well as proximity and
      orientation effects ensured sequential methylation of the substrate within the
      same pocket. Stepwise methylation of tricetin involves deprotonation of its
      hydroxyl groups by a His262-Asp263 pair followed by nucleophilic attack of SAM
      methyl groups. We also demonstrate that Val309, which is conserved in a number of
      graminaceous flavone OMTs, defines the preference of TaOMT2 for tricetin as the
      substrate. CONCLUSIONS: We propose a mechanism for the sequential methylation of
      tricetin, and discuss the potential application of TaOMT2 to increase the
      production of tricin as a nutraceutical. The single amino acid residue in TaOMT2,
      Val309, determines its preference for tricetin as the substrate, and may define
      the evolutionary differences between the two closely related proteins, COMT and
      flavone OMT.

PMID- 20670442
TI  - Regulation of early signaling and gene expression in the alpha-particle and
      bystander response of IMR-90 human fibroblasts.
AB  - BACKGROUND: The existence of a radiation bystander effect, in which non
      irradiated cells respond to signals from irradiated cells, is well established.
      To understand early signaling and gene regulation in bystander cells, we used a
      bio-informatics approach, measuring global gene expression at 30 minutes and
      signaling pathways between 30 minutes and 4 hours after exposure to alpha
      particles in IMR-90 fibroblasts. METHODS: We used whole human genome microarrays
      and real time quantitative PCR to measure and validate gene expression.
      Microarray analysis was done using BRB-Array Tools; pathway and ontology analyses
      were done using Ingenuity Pathway Analysis and PANTHER, respectively. We studied
      signaling in irradiated and bystander cells using immunoblotting and semi
      quantitative image analysis. RESULTS: Gene ontology suggested signal transduction
      and transcriptional regulation responding 30 minutes after treatment affected
      cell structure, motility and adhesion, and interleukin synthesis. We measured
      time-dependent expression of genes controlled by the NF-kappaB pathway; matrix
      metalloproteinases 1 and 3; chemokine ligands 2, 3 and 5 and interleukins 1beta,
      6 and 33. There was an increased response of this set of genes 30 minutes after
      treatment and another wave of induction at 4 hours. We investigated AKT-GSK3beta
      signaling and found both AKT and GSK3beta are hyper-phosphorylated 30 minutes
      after irradiation and this effect is maintained through 4 hours. In bystander
      cells, a similar response was seen with a delay of 30 minutes. We proposed a
      network model where the observed decrease in phosphorylation of beta-catenin
      protein after GSK3beta dependent inactivation can trigger target gene expression
      at later times after radiation exposure CONCLUSIONS: These results are the first
      to show that the radiation induced bystander signal induces a widespread gene
      expression response at 30 minutes after treatment and these changes are
      accompanied by modification of signaling proteins in the PI3K-AKT-GSK3beta
      pathway.

PMID- 20670443
TI  - Prediction of delayed recovery from pediatric community-acquired pneumonia.
AB  - BACKGROUND: If children with community-acquired pneumonia (CAP) do not recover
      within 48 hours after starting antibiotic therapy, complications are possible and
      a checkup must be ensured.Aim of the present study was to evaluate the
      improvement of pediatric CAP, within 48 hours after starting therapy, in relation
      to age, etiology, clinical/laboratory characteristics and selected antibiotics.
      METHODS: Ninety-four children were treated for radiologically confirmed CAP, 64
      by oral amoxicillin, 23 by intravenous ampicillin and 7 by other antibiotics. The
      etiology of CAP was studied by serology, data on more than 20 clinical
      characteristics were collected retrospectively, and antibiotics were selected on
      clinical grounds. RESULTS: After starting of antibiotics, the mean duration of
      fever was higher in children >or=5 than <2 or 2-4 years of age (p = 0.003). Fever
      continued >48 hours in 4 (4.3%) children and 2 additional children had empyema.
      Clinical, radiological and laboratory characteristics and serological findings
      were not significantly associated with the duration of fever. Fever continued >24
      hours in 1 (4.8%) child treated with ampicillin and in 2 (8%) inpatients compared
      with 19 (28.8%) children treated with amoxicillin (p = 0.007) and 23 (33%)
      outpatients (p = 0.0012), respectively. CONCLUSIONS: Respiratory rate and
      erythrocyte sedimentation rates were associated with rapid decrease of fever.
      Anyway, none of the reported characteristics was able to predict treatment
      failures or delayed fever decrease in children suffering from CAP.

PMID- 20670444
TI  - Association between expression of the bone morphogenetic proteins 2 and 7 in the
      repair of circumscribed cartilage lesions with clinical outcome.
AB  - BACKGROUND: Although there is much known about the role of BMPs in cartilage
      metabolism reliable data about the in vivo regulation in natural and surgically
      induced cartilage repair are still missing. METHODS: Lavage fluids of knee joints
      of 47 patients were collected during surgical therapy. 5 patients had no
      cartilage lesion and served as a control group, the other 42 patients with
      circumscribed cartilage defects were treated by microfracturing (19) or by an
      Autologous Chondrocyte Implantation (23). The concentrations of BMP-2 and BMP-7
      were determined by ELISA. The clinical status was evaluated using the IKDC Score
      prior to and 1 year following the operation. RESULTS: High level expression in
      the control group was found for BMP-2, concentrations of BMP-7 remained below
      detection levels. No statistical differences could be detected in concentrations
      of BMP-2 or BMP-7 in the lavage fluids of knees with cartilage lesions compared
      to the control group. Levels of BMP-7 did not change after surgical cartilage
      repair, whereas concentrations of BMP-2 statistically significant increased after
      the intervention (p < 0.001). The clinical outcome following cartilage
      regenerating surgery increased after 1 year by 29% (p < 0.001). The difference of
      the IKDC score after 1 year and prior to the operation was used to quantify the
      degree of improvement following surgery. This difference statistically
      significant correlated with initial BMP-2 (R = 0.554, p < 0.001) but not BMP-7 (R
      = 0.031, n.s.) levels in the knee joints. CONCLUSIONS: BMP-2 seems to play an
      important role in surgically induced cartilage repair; synovial expression
      correlates with the clinical outcome.

PMID- 20670445
TI  - Low grade fibromyxoid sarcoma: a case report and review of the literature.
AB  - Low grade fibromyxoid sarcoma (LGFMS) is a distinctive variant of fibrosarcoma
      with a high metastasizing potential and sometimes long interval between tumour
      presentation and metastasis. We present the case of a 50-year-old male who
      developed a large mass in the posterior aspect of his lower left thigh. The tumor
      was excised with preservation of the neurovascular structures surrounded by the
      mass. The tumour measured 11 x 10 x 9 cm and on pathology evaluation was
      diagnosed as LGFMS. Due to the relative rarity of LGFMS, there is no dedicated
      protocol regarding follow-up recommendations. In order to early diagnose possible
      metastasis it is important to inform the patients about the longstanding
      metastatic potential of the disease.

PMID- 20670447
TI  - Water and sanitation infrastructure for health: The impact of foreign aid.
AB  - BACKGROUND: The accessibility to improved water and sanitation has been
      understood as a crucial mechanism to save infants and children from the adverse
      health outcomes associated with diarrheal disease. This knowledge stimulated the
      worldwide donor community to develop a specific category of aid aimed at the
      water and sanitation sector. The actual impact of this assistance on increasing
      population access to improved water and sanitation and reducing child mortality
      has not been examined. METHODS: We performed a country-level analysis of the
      relationship between water and sanitation designated official development
      assistance (WSS-ODA) per capita, water and sanitation coverage, and infant and
      child mortality in low-income countries as defined by the World Bank. We focused
      our inquiry to aid effectiveness since the establishment of the Millennium
      Development Goals (MDGs). RESULTS: Access to improved water has consistently
      improved since 2002. Countries receiving the most WSS-ODA ranged from odds ratios
      of 4 to 18 times more likely than countries in the lowest tertile of assistance
      to achieve greater gains in population access to improved water supply. However,
      while there were modestly increased odds of sanitation access, these were largely
      non-significant. The countries with greatest gains in sanitation were 8-9 times
      more likely to have greater reductions in infant and child mortality.
      CONCLUSIONS: Official development assistance is importantly impacting access to
      safe water, yet access to improved sanitation remains poor. This highlights the
      need for decision-makers to be more intentional with allocating WSS-ODA towards
      sanitation projects.

PMID- 20670446
TI  - Gene expression profiling in the lungs of pigs with different susceptibilities to
      Glasser's disease.
AB  - BACKGROUND: Haemophilus parasuis is the causative agent of Glasser's disease in
      pigs. Currently, little is known about the molecular mechanisms that contribute
      to disease susceptibility. This study used a porcine oligonucleotide microarray
      to identify genes that were differentially expressed (DE) in the lungs of
      colostrum-deprived animals previously characterized as being either 'Fully
      Resistant' (FR) or 'Susceptible' to infection by H. parasuis in a bacterial
      challenge experiment. RESULTS: Gene expression profiles of 'FR' and 'Susceptible'
      animals were obtained by the identification of genes that were differentially
      expressed between each of these groups and mock-inoculated 'Control' animals. At
      24 hours post-inoculation, a total of 21 and 58 DE genes were identified in 'FR'
      and 'Susceptible' animals respectively. At 72 hours, the numbers of genes were 20
      and 347 respectively. 'FR' animals at 24 hours exhibited an increased expression
      of genes encoding extracellular matrix and TGF-beta signalling components,
      possibly indicative of tissue repair following the successful early resolution of
      infection. The gene expression profile of 'FR' animals at 72 hours supported the
      hypothesis that higher levels of antibacterial activity were responsible for the
      'FR' phenotype, possibly due to an increase in natural immunoglobulin A and
      decrease in signalling by the immunoregulatory transcription factor peroxisome
      proliferator-activated receptor gamma (PPAR-gamma). The expression profile of
      'Susceptible' animals at both time-points was characterized by an imbalance in
      signalling between pro and anti-inflammatory cytokines and an increased
      expression of genes involved in biological processes associated with
      inflammation. These include the pro-inflammatory cytokine genes resistin (RETN)
      and interleukin 1-beta (IL1B). At 72 hours, a reduction in the expression of
      genes involved in antigen presentation by both MHC class I and II molecules was
      observed, which could have contributed to the inability of 'Susceptible' animals
      to clear infection. CONCLUSIONS: This study is the first to have identified
      discrete sets of DE genes in pigs of differing susceptibility to H. parasuis
      infection. Consequently, several candidate genes and pathways for disease
      resistance or susceptibility phenotypes have been identified. In addition, the
      findings have shed light on the molecular pathology associated with Glasser's
      disease.

PMID- 20670448
TI  - Public health triangulation: approach and application to synthesizing data to
      understand national and local HIV epidemics.
AB  - BACKGROUND: Public health triangulation is a process for reviewing, synthesising
      and interpreting secondary data from multiple sources that bear on the same
      question to make public health decisions. It can be used to understand the
      dynamics of HIV transmission and to measure the impact of public health programs.
      While traditional intervention research and meta-analysis would be ideal sources
      of information for public health decision making, they are infrequently
      available, and often decisions can be based only on surveillance and survey data.
      METHODS: The process involves examination of a wide variety of data sources and
      both biological, behavioral and program data and seeks input from stakeholders to
      formulate meaningful public health questions. Finally and most importantly, it
      uses the results to inform public health decision-making. There are 12 discrete
      steps in the triangulation process, which included identification and assessment
      of key questions, identification of data sources, refining questions, gathering
      data and reports, assessing the quality of those data and reports, formulating
      hypotheses to explain trends in the data, corroborating or refining working
      hypotheses, drawing conclusions, communicating results and recommendations and
      taking public health action. RESULTS: Triangulation can be limited by the quality
      of the original data, the potentials for ecological fallacy and "data dredging"
      and reproducibility of results. CONCLUSIONS: Nonetheless, we believe that public
      health triangulation allows for the interpretation of data sets that cannot be
      analyzed using meta-analysis and can be a helpful adjunct to surveillance, to
      formal public health intervention research and to monitoring and evaluation,
      which in turn lead to improved national strategic planning and resource
      allocation.

PMID- 20670449
TI  - Dimensional and hierarchical models of depression using the Beck Depression
      Inventory-II in an Arab college student sample.
AB  - BACKGROUND: An understanding of depressive symptomatology from the perspective of
      confirmatory factor analysis (CFA) could facilitate valid and interpretable
      comparisons across cultures. The objectives of the study were: (i) using the
      responses of a sample of Arab college students to the Beck Depression Inventory
      (BDI-II) in CFA, to compare the "goodness of fit" indices of the original
      dimensional three-and two-factor first-order models, and their modifications,
      with the corresponding hierarchical models (i.e., higher - order and bifactor
      models); (ii) to assess the psychometric characteristics of the BDI-II, including
      convergent/discriminant validity with the Hopkins Symptom Checklist (HSCL-25).
      METHOD: Participants (N = 624) were Kuwaiti national college students, who
      completed the questionnaires in class. CFA was done by AMOS, version 16. Eleven
      models were compared using eight "fit" indices. RESULTS: In CFA, all the models
      met most "fit" criteria. While the higher-order model did not provide improved
      fit over the dimensional first - order factor models, the bifactor model (BFM)
      had the best fit indices (CMNI/DF = 1.73; GFI = 0.96; RMSEA = 0.034). All
      regression weights of the dimensional models were significantly different from
      zero (P < 0.001). Standardized regression weights were mostly 0.27-0.60, and all
      covariance paths were significantly different from zero. The regression weights
      of the BFM showed that the variance related to the specific factors was mostly
      accounted for by the general depression factor, indicating that the general
      depression score is an adequate representation of severity. The BDI-II had
      adequate internal consistency and convergent/discriminant validity. The mean BDI
      score (15.5, SD = 8.5) was significantly higher than those of students from other
      countries (P < 0.001). CONCLUSION: The broadly adequate fit of the various models
      indicates that they have some merit and implies that the relationship between the
      domains of depression probably contains hierarchical and dimensional elements.
      The bifactor model is emerging as the best way to account for the clinical
      heterogeneity of depression. The psychometric characteristics of the BDI-II lend
      support to our CFA results.

PMID- 20670451
TI  - Banha-sasim-tang as an herbal formula for the treatment of functional dyspepsia:
      a randomized, double-blind, placebo-controlled, two-center trial.
AB  - BACKGROUND: Functional dyspepsia (FD) is characterized by a high prevalence rate
      and no standard conventional treatments. Alternative therapies, such as herbal
      formulas, are widely used to treat FD. However, there are inadequate evidences
      regarding the safety and efficacy of these formulas. Moreover, the mechanisms by
      which herbal formulas act in the gastrointestinal tract are controversial. In
      traditional Korean medicine, Banha-sasim-tang has long been one of the most
      frequently prescribed herbal formulas for treating dyspepsia. The current study
      is designed to evaluate the efficacy and safety of Banha-sasim-tang for FD
      patients and to examine whether there will be a significant correlation between
      cutaneous electrogastrography recordings and dyspeptic symptoms in FD patients,
      and between changes in gastric myoelectrical activity and improvement in
      dyspeptic symptoms during Banha-sasim-tang administration. METHODS: This
      randomized, double-blind, placebo-controlled trial will be performed at two
      centers and will include a Banha-sasim-tang group and placebo group. Each group
      will consist of 50 FD patients. Six weeks of administration of Banha-sasim-tang
      or placebo will be conducted. During the subsequent 2 months, follow-up
      observations of primary and secondary outcomes will be performed. The primary
      outcomes are differences as measured on the gastrointestinal symptom scale, and
      the secondary outcomes are differences as measured on the visual analogue scale
      for dyspepsia and on the questionnaire for FD-related quality of life. All
      outcomes will be measured at baseline, at 2, 4, and 6 weeks of treatment, and at
      the 1 and 2 month follow-up. Cutaneous electrogastrography will be performed and
      assessed at baseline and at 6 weeks. DISCUSSION: This trial will provide evidence
      of the safety and efficacy of Banha-sasim-tang for the treatment for FD.
      Furthermore, based on the assessment of the relationship between cutaneous
      electrogastrography recordings and dyspeptic symptoms in this trial, the
      possibility of clinical applications of cutaneous electrogastrography in the
      treatment of FD will be elucidated. TRIAL REGISTRATION: Current Controlled Trials
      (ISRCTN 51910678); Clinical Trials.gov Identifier: NCT00987805.

PMID- 20670450
TI  - Microarray analysis of response of Salmonella during infection of HLA-B27-
      transfected human macrophage-like U937 cells.
AB  - BACKGROUND: Human leukocyte antigen (HLA)-B27 is strongly associated with the
      development of reactive arthritis (ReA) in humans after salmonellosis. Human
      monocytic U937 cells transfected with HLA-B27 are less able to eliminate
      intracellular Salmonella enterica serovar Enteritidis than those transfected with
      control HLA antigens (e.g. HLA-A2). To investigate further the mechanisms by
      which HLA-B27-transfected cells allow increased replication of these bacteria, a
      DNA-based microarray was used for comparative genomic analysis of S. Enteritidis
      grown in HLA-B27- or HLA-A2-transfected cells. The microarray consisted of 5080
      oligonucleotides from different serovars of Salmonella including S. Enteritidis
      PT4-specific genes. Bacterial RNA was isolated from the infected HLA-B27- or HLA
      A2-transfected cells, reverse-transcribed to cDNA, and hybridized with the
      oligonucleotides on the microarrays. Some microarray results were confirmed by RT
      PCR. RESULTS: When gene expression was compared between Salmonella grown in HLA
      B27 cells and in HLA-A2 cells, 118 of the 4610 S. Enteritidis-related genes
      differed in expression at 8 h after infection, but no significant difference was
      detectable at 2 h after infection. These differentially expressed genes are
      mainly involved in Salmonella virulence, DNA replication, energy conversion and
      metabolism, and uptake and metabolism of nutrient substances, etc. The difference
      suggests HLA-B27-dependent modulation of Salmonella gene expression, resulting in
      increased Salmonella replication in HLA-B27-positive cells. Among the up
      regulated genes were those located in Salmonella pathogenicity island (SPI)-2,
      which play a central role in intracellular survival and replication of
      Salmonella. CONCLUSIONS: This is the first report to show the regulation of
      Salmonella gene expression by HLA-B27 during infection of host cells. This
      regulation probably leads to increased Salmonella survival and replication in HLA
      B27-positive cells. SPI-2 genes seem to contribute significantly to the increased
      replication.

PMID- 20670452
TI  - The process evaluation of It's Your Move!, an Australian adolescent community
      based obesity prevention project.
AB  - BACKGROUND: Evidence on interventions for preventing unhealthy weight gain in
      adolescents is urgently needed. The aim of this paper is to describe the process
      evaluation for a three-year (2005-2008) project conducted in five secondary
      schools in the East Geelong/Bellarine region of Victoria, Australia. The project,
      'It's Your Move!' aimed to reduce unhealthy weight gain by promoting healthy
      eating patterns, regular physical activity, healthy body weight, and body size
      perception amongst youth; and improve the capacity of families, schools, and
      community organisations to sustain the promotion of healthy eating and physical
      activity in the region. METHODS: The project was supported by Deakin University
      (training and evaluation), a Reference Committee (strategic direction, budgetary
      approval and monitoring) and a Project Management Committee (project delivery). A
      workshop of students, teachers and other stakeholders formulated a 10-point
      action plan, which was then translated into strategies and initiatives specific
      to each school by the School Project Officers (staff members released from
      teaching duties one day per week) and trained Student Ambassadors. Baseline
      surveys informed intervention development. Process data were collected on all
      intervention activities and these were collated and enumerated, where possible,
      into a set of mutually exclusive tables to demonstrate the types of strategies
      and the dose, frequency and reach of intervention activities. RESULTS: The action
      plan included three guiding objectives, four on nutrition, two on physical
      activity and one on body image. The process evaluation data showed that a mix of
      intervention strategies were implemented, including social marketing, one-off
      events, lunch time and curriculum programs, improvements in infrastructure, and
      healthy school food policies. The majority of the interventions were implemented
      in schools and focused on capacity building and healthy eating strategies as
      physical activity practices were seen by the teachers as already meeting
      students' needs. CONCLUSIONS: While substantial health-promoting activities were
      conducted (especially related to healthy eating), there remain further
      opportunities for secondary schools to use a whole-of-school approach through the
      school curriculum, environment, policies and ethos to improve healthy eating,
      physical activity and healthy body perceptions in youth. To achieve this,
      significant, sustained leadership will be required within the education sector
      generally and within schools specifically.

PMID- 20670453
TI  - Risk factors for multi-drug resistant Acinetobacter baumannii bacteremia in
      patients with colonization in the intensive care unit.
AB  - BACKGROUND: Epidemic outbreaks of multi-drug resistant (MDR) Acinetobacter
      baumannii (AB) in intensive care units (ICUs) are increasing. The incidence of
      MDR AB bacteremia, which develops as a result of colonization, is increasing
      through widespread dissemination of the pathogen, and further colonization. We
      sought to determine risk factors for MDR AB bacteremia in patients colonized with
      MDR AB in the ICU. METHODS: We conducted a retrospective, observational study of
      200 patients colonized with MDR AB in the ICU at Severance Hospital, South Korea
      during the outbreak period between January 2008 and December 2009. RESULTS: Of
      the 200 patients colonized with MDR AB, 108 developed MDR AB bacteremia, and 92
      did not. APACHE II scores were higher in bacteremic than non-bacteremic patients
      at the time of ICU admission and colonization (24.0 vs. 21.6; P = 0.035, 22.9 vs.
      16.8; P < 0.001, respectively). There was no difference between the two groups in
      the duration of time from ICU admission to colonization (7.1 vs. 7.2 days; P =
      0.923), but the duration of time at risk was shorter in bacteremic patients (12.1
      vs. 6.0 days; P = 0.016). A recent invasive procedure was a significant risk
      factor for development of bacteremia (odds ratio = 3.85; 95% CI 1.45-10.24; P =
      0.007). Multivariate analysis indicated infection and respiratory failure at the
      time of ICU admission, maintenance of mechanical ventilation, maintenance of
      endotracheal tube instead of switching to a tracheostomy, recent central venous
      catheter insertion, bacteremia caused by other microorganism after colonization
      by MDR AB, and prior antimicrobial therapy, were significant risk factors for MDR
      AB bacteremia. CONCLUSIONS: Patients in the ICU, colonized with MDR AB, should be
      considered for minimizing invasive procedures and early removal of the invasive
      devices to prevent development of MDR AB bacteremia.

PMID- 20670454
TI  - Basement membrane and vascular remodelling in smokers and chronic obstructive
      pulmonary disease: a cross-sectional study.
AB  - BACKGROUND: Little is known about airway remodelling in bronchial biopsies (BB)
      in smokers and chronic obstructive pulmonary disease (COPD). We conducted an
      initial pilot study comparing BB from COPD patients with nonsmoking controls.
      This pilot study suggested the presence of reticular basement membrane (Rbm)
      fragmentation and altered vessel distribution in COPD. METHODS: To determine
      whether Rbm fragmentation and altered vessel distribution in BB were specific for
      COPD we designed a cross-sectional study and stained BB from 19 current smokers
      and 14 ex-smokers with mild to moderate COPD and compared these to 15 current
      smokers with normal lung function and 17 healthy and nonsmoking subjects.
      RESULTS: Thickness of the Rbm was not significantly different between groups;
      although in COPD this parameter was quite variable. The Rbm showed fragmentation
      and splitting in both current smoking groups and ex-smoker COPD compared with
      healthy nonsmokers (p < 0.02); smoking and COPD seemed to have additive effects.
      Rbm fragmentation correlated with smoking history in COPD but not with age. There
      were more vessels in the Rbm and fewer vessels in the lamina propria in current
      smokers compared to healthy nonsmokers (p < 0.05). The number of vessels staining
      for vascular endothelial growth factor (VEGF) in the Rbm was higher in both
      current smoker groups and ex-smoker COPD compared to healthy nonsmokers (p <
      0.004). In current smoker COPD VEGF vessel staining correlated with FEV1%
      predicted (r = 0.61, p < 0.02). CONCLUSIONS: Airway remodelling in smokers and
      mild to moderate COPD is associated with fragmentation of the Rbm and altered
      distribution of vessels in the airway wall. Rbm fragmentation was also present to
      as great an extent in ex-smokers with COPD. These characteristics may have
      potential physiological consequences.

PMID- 20670455
TI  - Prevalence and characterization of plasmids carrying sulfonamide resistance genes
      among Escherichia coli from pigs, pig carcasses and human.
AB  - BACKGROUND: Sulfonamide resistance is very common in Escherichia coli. The aim of
      this study was to characterize plasmids carrying sulfonamide resistance genes
      (sul1, sul2 and sul3) in E. coli isolated from pigs and humans with a specific
      objective to assess the genetic diversity of plasmids involved in the mobility of
      sul genes. METHODS: A total of 501 E. coli isolates from pig feces, pig carcasses
      and human stools were tested for their susceptibility to selected antimicrobial.
      Multiplex PCR was conducted to detect the presence of three sul genes among the
      sulfonamide-resistant E. coli isolates. Fifty-seven sulfonamide-resistant E. coli
      were selected based on presence of sul resistance genes and subjected to
      conjugation and/or transformation experiments. S1 nuclease digestion followed by
      pulsed-field gel electrophoresis was used to visualize and determine the size of
      plasmids. Plasmids carrying sul genes were characterized by PCR-based replicon
      typing to allow a comparison of the types of sul genes, the reservoir and plasmid
      present. RESULTS: A total of 109/501 isolates exhibited sulfonamide resistance.
      The relative prevalences of sul genes from the three reservoirs (pigs, pig
      carcasses and humans) were 65%, 45% and 12% for sul2, sul1, and sul3,
      respectively. Transfer of resistance through conjugation was observed in 42/57
      isolates. Resistances to streptomycin, ampicillin and trimethoprim were co
      transferred in most strains. Class 1 integrons were present in 80% of sul1
      carrying plasmids and 100% of sul3-carrying plasmids, but only in 5% of sul2
      carrying plasmids. The sul plasmids ranged from 33 to 160-kb in size and belonged
      to nine different incompatibility (Inc) groups: FII, FIB, I1, FIA, B/O, FIC, N,
      HI1 and X1. IncFII was the dominant type in sul2-carrying plasmids (52%), while
      IncI1 was the most common type in sul1 and sul3-carrying plasmids (33% and 45%,
      respectively). Multireplicons were found associated with all three sul genes.
      CONCLUSIONS: Sul genes were distributed widely in E. coli isolated from pigs and
      humans with sul2 being most prevalent. Sul-carrying plasmids belonged to diverse
      replicon types, but most of detected plasmids were conjugative enabling
      horizontal transfer. IncFII seems to be the dominant replicon type in sul2
      carrying plasmids from all three sources.

PMID- 20670456
TI  - Prospective study of determinants and costs of home births in Mumbai slums.
AB  - BACKGROUND: Around 86% of births in Mumbai, India, occur in healthcare
      institutions, but this aggregate figure hides substantial variation and little is
      known about urban home births. We aimed to explore factors influencing the choice
      of home delivery, care practices and costs, and to identify characteristics of
      women, households and the environment which might increase the likelihood of home
      birth. METHODS: As part of the City Initiative for Newborn Health, we used a key
      informant surveillance system to identify births prospectively in 48 slum
      communities in six wards of Mumbai, covering a population of 280,000. Births and
      outcomes were documented prospectively by local women and mothers were
      interviewed in detail at six weeks after delivery. We examined the prevalence of
      home births and their associations with potential determinants using regression
      models. RESULTS: We described 1708 (16%) home deliveries among 10,754 births over
      two years, 2005-2007. The proportion varied from 6% to 24%, depending on area.
      The most commonly cited reasons for home birth were custom and lack of time to
      reach a healthcare facility during labour. Seventy percent of home deliveries
      were assisted by a traditional birth attendant (dai), and 6% by skilled health
      personnel. The median cost of a home delivery was US$ 21, of institutional
      delivery in the public sector US$ 32, and in the private sector US$ 118. In an
      adjusted multivariable regression model, the odds of home delivery increased with
      illiteracy, parity, socioeconomic poverty, poorer housing, lack of water supply,
      population transience, and hazardous location. CONCLUSIONS: We estimate 32,000
      annual home births to residents of Mumbai's slums. These are unevenly distributed
      and cluster with other markers of vulnerability. Since cost does not appear to be
      a dominant disincentive to institutional delivery, efforts are needed to improve
      the client experience at public sector institutions. It might also be productive
      to concentrate on intensive outreach in vulnerable areas by community-based
      health workers, who could play a greater part in helping women plan their
      deliveries and making sure that they get help in time.

PMID- 20670457
TI  - Entropy of balance--some recent results.
AB  - BACKGROUND: Entropy when applied to biological signals is expected to reflect the
      state of the biological system. However the physiological interpretation of the
      entropy is not always straightforward. When should high entropy be interpreted as
      a healthy sign, and when as marker of deteriorating health? We address this
      question for the particular case of human standing balance and the Center of
      Pressure data. METHODS: We have measured and analyzed balance data of 136
      participants (young, n = 45; elderly, n = 91) comprising in all 1085 trials, and
      calculated the Sample Entropy (SampEn) for medio-lateral (M/L) and anterior
      posterior (A/P) Center of Pressure (COP) together with the Hurst self-similarity
      (ss) exponent alpha using Detrended Fluctuation Analysis (DFA). The COP was
      measured with a force plate in eight 30 seconds trials with eyes closed, eyes
      open, foam, self-perturbation and nudge conditions. RESULTS: 1) There is a
      significant difference in SampEn for the A/P-direction between the elderly and
      the younger groups Old > young. 2) For the elderly we have in general A/P > M/L.
      3) For the younger group there was no significant A/P-M/L difference with the
      exception for the nudge trials where we had the reverse situation, A/P < M/L. 4)
      For the elderly we have, Eyes Closed > Eyes Open. 5) In case of the Hurst ss
      exponent we have for the elderly, M/L > A/P. CONCLUSIONS: These results seem to
      be require some modifications of the more or less established attention
      constraint interpretation of entropy. This holds that higher entropy correlates
      with a more automatic and a less constrained mode of balance control, and that a
      higher entropy reflects, in this sense, a more efficient balancing.

PMID- 20670458
TI  - Prevalence of neck pain in subjects with metabolic syndrome--a cross-sectional
      population-based study.
AB  - BACKGROUND: Metabolic syndrome (MetS) is increasingly common. Obesity has been
      suggested to associate with neck pain but prevalence of neck pain in subjects
      with MetS has not been studied. Aim of this study was to analyse the association
      between MetS and neck pain. METHODS: The study population consisted of 1294
      middle-aged subjects in Pieksamaki, Finland. A total of 399 males and 500 females
      participated (69%). The mean age of both males and females was 46 years. Clinical
      and biochemical measurements were taken. The participants filled out a standard
      questionnaire. Psychological distress was assessed with the 12-item General
      Health Questionnaire (GHQ-12). Neck pain was defined as neck pain perceived
      daily. MetS was defined using National Cholesterol Education Program (NCEP)
      criteria. Statistical comparisons between the groups were performed using a
      bootstrap-type t-test or Chi-Square test. Risk ratios of having neck pain were
      calculated using generalised linear models with age, smoking, alcohol use,
      exercise and GHQ-12 score as covariates. RESULTS: The prevalence of MetS was 33%
      in males and 29% in females. Neck pain was present in 11% (N = 42) of males and
      19% (N = 93) of females (P < 0.001). The prevalence of neck pain was 7.9% (95%
      CI, 4.9% to 12%) among male subjects without MetS and 16% (95% CI, 10% to 23%)
      among those with MetS. The respective proportions among females were 16% (95% CI,
      12% to 20%) and 25% (95% CI, 18% to 33%). The multivariate analysis showed an
      increased risk of neck pain in males with MetS (RR 2.1, 95% CI, 1.2 to 3.7, P =
      0.010) and in females with MetS (RR 1.5, 95% CI, 1.0 to 2.1, P = 0.040).
      CONCLUSIONS: MetS was associated with neck pain. This association was stronger in
      males, but the prevalence of neck pain was higher in females. Prospective studies
      should explore the potential causal association between neck pain and MetS and
      the potential common background factors of neck pain and MetS.

PMID- 20670459
TI  - Polystoma okomuensis n. sp. (Monogenea: Polystomatidae) from Boulenger's striped
      frog, Phlyctimantis boulengeri (Perret, 1986) in Nigeria.
AB  - Polystoma okomuensis is described as a new species of the Polystomatidae
      parasitic in the urinary bladder of Boulenger's striped frog Phlyctimantis
      boulengeri in the Okomu National Park, Edo State, Nigeria. Although other African
      polystomes have been reported from Nigeria, this is the first to be described
      from the country and the first from Phlyctimantis. It is distinguished from other
      African Polystoma species by a combination of characters, including the body
      size, size and shape of the hamuli, size and shape of marginal hooklets and
      intestinal location. Phlyctimantis boulengeri was found to be infected in two of
      four seasonal lakes where specimens were caught with prevalences and mean
      intensities ranging from 14.3 to 22% and 1.0 to 1.5, respectively. Of the total
      number of 45 frogs examined, the prevalence was 15.6% and mean intensity 1.4.

PMID- 20670460
TI  - Can older "at risk" adults benefit from psychoeducation targeting healthy brain
      aging?
AB  - BACKGROUND: Multifactorial strategies that prevent or delay the onset or progress
      of cognitive decline and dementia are needed, and should include education
      regarding recognized risk factors. The current study sought to investigate
      whether older adults "at risk" of cognitive decline benefit from psychoeducation
      targeting healthy brain aging. METHODS: 65 participants (mean age 64.8 years, SD
      9.6) with a lifetime history of major depression; vascular risk as evidenced by
      at least one vascular risk factor; and/or subjective or objective memory
      impairment were allocated to weekly psychoeducation sessions or a waitlist
      control group. The small group sessions were conducted over ten weeks by a team
      of medical and allied health professionals with expertise in late-life depression
      and cognition. Sessions focused on modifiable risk factors for cognitive decline
      including vascular risk, diet, exercise, depression, anxiety and sleep
      disturbance, as well as providing practical strategies for memory and cognition.
      Both the psychoeducation and waitlist group completed a 20-item knowledge test at
      baseline and follow-up. Participants in the psychoeducation group were asked to
      complete follow-up self-report satisfaction questionnaires. RESULTS: Repeated
      measures ANOVA showed a significant interaction effect depicting improvements in
      knowledge associated with psychoeducation, corresponding to an improvement of 15%
      from baseline. Satisfaction data additionally showed that 92.3% of participants
      rated the program as "good" to "excellent", and over 90% suggested they would
      recommend it to others. CONCLUSIONS: A group-based psychoeducation program
      targeting healthy brain aging is effective in improving knowledge. Additionally,
      it is acceptable and rated highly by participants.

PMID- 20670461
TI  - Prescribing trends in cognition enhancing drugs in Australia.
AB  - BACKGROUND: This study sought to examine the trends in the prescribing of
      subsidized and unsubsidized cognition enhancing drugs (CEDs) in Australia over
      five years from 2002 to 2007. Subsidized cholinesterase inhibitor medication
      could be prescribed to people with mild to moderate Alzheimer's disease (AD) once
      a specialist physician had confirmed this diagnosis. Memantine was available for
      use in moderately severe AD but not subsidized. METHODS: We analyzed the Medicare
      Australia and Drug Utilisation Sub-Committee databases for CED prescription data,
      2002-2007, by gender, age and prescriber class. Aggregated prescription data for
      each medication were converted to defined daily doses (DDD) per 1000 persons per
      day using national census data. RESULTS: There were 1,583,667 CED prescriptions
      dispensed during the study period. CED use increased 58% from 0.91 to 1.56
      DDD/1000 persons/day between 2002 and 2007. Peak use was in those aged 85-89
      years. Age-adjusted utilization was slightly higher in females than males.
      Donepezil was the most widely used CED (66%), followed by galantamine (27%) then
      memantine (4%). General practitioners prescribed the majority of CEDs.
      Geriatricians exhibited a greater preference for galantamine than other
      prescribers. CED dispensing peaked towards the end of each calendar year,
      reflecting stockpiling by patients under the influence of a federal safety net
      subsidy. CONCLUSIONS: Despite subsidized access to CEDs in Australia, only a
      minority of people with AD was prescribed these drugs during the period of the
      study. It is likely that the combination of complex prescribing rules and
      negative perceptions about efficacy or cost-effectiveness might have contributed
      to these findings.

PMID- 20670462
TI  - Evaluation of Alzheimer's Australia Vic Memory Lane Cafes.
AB  - BACKGROUND: This paper describes the evaluation of the Memory Lane Cafe service
      in Victoria, Australia. The Alzheimer's Australia Vic Memory Lane Cafe model aims
      to provide a social and educational service to people living with dementia and
      their carers, family members or friends. Dementia is a serious health issue in
      Australia, with prevalence estimated at 6.5% of people over 65 years of age.
      Living with dementia has significant social and psychological ramifications,
      often negatively affecting quality of life. Social support groups can improve
      quality of life for people living with dementia. METHODS: The evaluation included
      focus groups and surveys of people with dementia and their carers, staff
      consultation, service provider interviews, and researcher observation. The
      Melbourne Health Mental Health Human Research Ethics Committee approved the
      project. Participants included people with dementia (aged 60 to 93 years,
      previously enrolled in the Alzheimer's Australia Vic's six-week Living With
      Memory Loss Program), their carers, friends and/or family members, staff working
      in the Cafes, and service providers with links to the Cafes. RESULTS: This
      evaluation found that Memory Lane Cafes promote social inclusion, prevent
      isolation, and improve the social and emotional well-being of attendees. However,
      Cafes did not meet the needs of all potential attendees. CONCLUSIONS: The
      evaluation recommended that existing Cafe services be continued and possibilities
      for extending the Cafes be explored. Based on evaluation outcomes, the Department
      of Health Victoria is funding four additional pilot programs in cafe style
      support services.

PMID- 20670463
TI  - Pathways to inflated responsibility beliefs, responsibility attitudes and
      obsessive-compulsive symptoms: factor structure and test of a mediational model.
AB  - INTRODUCTION: Inflated responsibility has been hypothesized as an important
      influence on OCD symptoms. According to Salkovskis and colleagues (1999) there
      are in turn five developmental pathways that lead to inflated responsibility.
      Coles and Schofield (2008) proposed the Pathways to Responsibility Beliefs Scale
      (PIRBS) as a measure of these pathways. METHOD: In the present study the
      psychometric properties of an Icelandic translation of the PIRBS were evaluated
      and its factor structure was studied in a confirmatory factor analysis. Further
      it was tested whether responsibility mediated between pathways to responsibility
      beliefs and OCD symptoms. RESULTS: While neither a four nor a five-factor
      structure of the PIRBS was found to be wholly satisfactory; support for the
      latter was slightly better. Correlations of the PIRBS scales with measures of
      responsibility and obsessive-compulsive disorder symptoms were moderate as
      expected. Support was found for a mediating role of responsibility attitudes
      between pathways measured by the PIRBS and OCD symptoms in support of Salkovskis
      and colleagues' theory (1999). CONCLUSION: The PIRBS is a promising approach to
      study the developmental precursors of inflated responsibility and OCD symptoms
      but its factor structure may need a revision.

PMID- 20670464
TI  - Influence of blue light on the leaf morphoanatomy of in vitro Kalanchoe pinnata
      (Lamarck) Persoon (Crassulaceae).
AB  - Kalanchoe pinnata (Lamarck) Persoon (Crassulaceae) (air plant, miracle leaf) is
      popularly used to treat gastrointestinal disorders and wounds. Recently, the
      species was tested to treat cutaneous leishmaniasis with successful results. This
      medicinal activity was associated with the phenolic fraction of the plant. Blue
      light induces biosynthesis of phenolic compounds and many changes in anatomical
      characteristics. We studied the effects of supplementary blue light on the leaf
      morphology of in vitro K. pinnata. Plants cultured under white light (W plants)
      only and white light plus blue light (WB plants) show petioles with plain-convex
      section, amphistomatic leaf blades with simple epidermis, homogeneous mesophyll
      with densely packed cells, and a single collateral vascular bundle in the midrib.
      W plants have longer branches, a larger number of nodes per branch, and smaller
      leaves, whereas WB plant leaves have a thicker upper epidermis and mesophyll.
      Leaf fresh weight and leaf dry weight were similar in both treatments. Phenolic
      idioblasts were observed in the plants supplemented with blue light, suggesting
      that blue light plays an important role in the biosynthesis of phenolic compounds
      in K. pinnata.

PMID- 20670465
TI  - Atom scale characterization of the near apex region of an atomic force microscope
      tip.
AB  - Three-dimensional atom probe tomography (APT) is successfully used to analyze the
      near-apex regions of an atomic force microscope (AFM) tip. Atom scale material
      structure and chemistry from APT analysis for standard silicon AFM tips and
      silicon AFM tips coated with a thin film of Cu is presented. Comparison of the
      thin film data with that observed using transmission electron microscopy
      indicates that APT can be reliably used to investigate the material structure and
      chemistry of the apex of an AFM tip at near atomic scales.

PMID- 20670466
TI  - Long-term effects on haemostatic variables of three ad libitum diets differing in
      type and amount of fat and carbohydrate: a 6-month randomised study in obese
      individuals.
AB  - Diet is important in the prevention of CVD, and it has been suggested that a diet
      high in MUFA is more cardioprotective than a low-fat diet. We hypothesised that
      the thrombotic risk profile is improved most favourably by a high-MUFA diet
      compared with a low-fat diet. This was tested in a parallel randomised
      intervention trial on overweight individuals (aged 28.2 (sd 4.6) years) randomly
      assigned to a diet providing a moderate amount of fat (35-45 % of energy; >20 %
      of fat as MUFA) (MUFA diet; n 39), to a low-fat (LF; 20-30 % of energy) diet (n
      43), or to a control diet (35 % of energy as fat; n 24) for 6 months after a
      weight loss of about 10 %. Protein constituted 10-20 % of energy in all three
      diets. All foods were provided free of charge from a purpose-built supermarket.
      Fasting blood samples were collected before and after intervention and analysed
      for factor VII coagulant activity (FVII:c), fibrinogen, prothrombin fragment 1+2
      (F1+2), D-dimer and plasminogen activator inhibitor (PAI). The fibrinogen
      concentration was significantly lowered by the LF diet, but not by the MUFA diet.
      Changes in fibrinogen differed significantly between diet groups. BMI and PAI
      concentration increased and D-dimer concentrations were reduced irrespective of
      the diets. No changes were observed for FVII:c and F1+2. Our findings suggest
      that in overweight subjects after weight loss the thrombotic risk profile is
      improved most favourably by the LF diet compared with the MUFA diet based on the
      reduction in fibrinogen concentrations.

PMID- 20670467
TI  - Emergence of dengue virus type 4 (genotype I) in India.
AB  - Dengue is an emerging arboviral disease and currently poses the greatest
      arboviral threat to human health. In recent decades, there has been a substantial
      increase in dengue outbreaks in many parts of the world including India. We
      performed an in-depth investigation of a major dengue outbreak in Andhra Pradesh,
      southern India in 2007 by serology, virus isolation, RT-PCR and genotyping. The
      results revealed an unusual emergence of dengue virus type 4 (DENV-4) along with
      the prevailing DENV-3. Phylogenetic analysis based on complete envelope gene of
      182 globally diverse DENV-4 isolates demonstrated the involvement of a unique
      clade of genotype I of DENV-4 in the outbreak. This study also demonstrated a
      clear shift in the dominant serotype from DENV-3 to DENV-4 in India. This is the
      first report regarding the molecular characterization of Indian isolates of DENV
      4, which has the potential to be involved in future outbreaks.

PMID- 20670468
TI  - Role of probiotic in preventing acute diarrhoea in children: a community-based,
      randomized, double-blind placebo-controlled field trial in an urban slum.
AB  - Acute diarrhoea remains a major public health challenge in developing countries.
      We examined the role of a probiotic in the prevention of acute diarrhoea to
      discover if there was an effect directed towards a specific aetiology. A double
      blind, randomized, controlled field trial involving 3758 children aged 1-5 years
      was conducted in an urban slum community in Kolkata, India. Participants were
      given either a probiotic drink containing Lactobacillus casei strain Shirota or a
      nutrient drink daily for 12 weeks. They were followed up for another 12 weeks.
      The primary outcome of this study was the occurrence of first episodes of
      diarrhoea. We assessed this during 12 weeks of intake of study agent and also for
      12 weeks of follow-up. There were 608 subjects with diarrhoea in the probiotic
      group and 674 subjects in the nutrient group during the study period of 24 weeks.
      The level of protective efficacy for the probiotic was 14% (95% confidence
      interval 4-23, P<0.01 in adjusted model). The reduced occurrence of acute
      diarrhoea in the probiotic group compared to nutrient group was not associated
      with any specific aetiology. No adverse event was observed in children of either
      probiotic or nutrient groups. The study suggests that daily intake of a probiotic
      drink can play a role in prevention of acute diarrhoea in young children in a
      community setting of a developing country.

PMID- 20670469
TI  - West Nile virus circulation in Veneto region in 2008-2009.
AB  - West Nile virus (WNV) was detected in Italy, in late summer 2008 in horses and
      birds in the Po valley. As a consequence, an intense WNV surveillance was
      implemented in that area involving Emilia-Romagna, Veneto and Lombardy. This
      paper presents the results of the September 2008-November 2009 surveillance on
      equines, mosquitoes, wild birds, dogs and cattle in Veneto. WNV was detected in
      equines and dogs, and, to a lesser extent in cattle and wild birds. Simultaneous
      circulation of Usutu virus was detected by testing wild birds found dead. Usutu
      virus but not WNV was also found in mosquitoes monitored during 2009. Equine
      practices monitoring allowed the definition of an area of WNV circulation and the
      2008-2009 westward and northward spread of the infection. Although a relatively
      low number of human cases and a low virus circulation in vectors and birds
      detected in Veneto region could be considered favourable conditions for a limited
      risk of human exposure, it remains difficult to predict the possible evolution of
      the epidemiological situation.

PMID- 20670470
TI  - Altered Fos immunoreactivity in the hypothalamus after glucose administration in
      pre- and post-weaning malnourished rats.
AB  - The present study explored the effects of malnutrition and nutritional
      rehabilitation on the response to glucose in hypothalamic nuclei involved in
      metabolic homeostasis. Male Wistar rats were malnourished during gestation
      lactation (MGL) or at weaning to 55 days (MPW). Two groups of rats were
      rehabilitated with a balanced diet until 90 days (MGL-R and MPW-R, respectively).
      After a glucose tolerance test (GTT), brains were processed for Fos
      immunoreactivity (Fos-IR). Both malnourished groups displayed hyperglycemia after
      GTT. MGL exhibited an increased number of Fos-IR neurons in the ventromedial
      hypothalamic nucleus (VMH), while MPW showed increased Fos-IR in the arcuate
      nucleus (ARC) and VMH and a decrease in the paraventricular nucleus (PVN), as
      compared with their controls. Nutritional rehabilitation normalized values of
      glucose after GTT in both groups, while low number of Fos-IR neurons remained in
      the ARC, PVN and VMH of MPW-R rats, indicating a deleterious, long-lasting effect
      after post-weaning malnutrition.

PMID- 20670472
TI  - Maternal malnutrition during lactation alters gonadotropin-releasing hormone
      expression in the hypothalamus of weaned male rat pups.
AB  - Gonadotropin-releasing hormone (GnRH) is the key hormone regulating reproduction.
      Its feedback regulation is exercised by estradiol. The early postnatal period is
      critical for sexual differentiation. Despite the fact that malnutrition-related
      reproductive suppression in rats is a well-documented phenomenon, we had no
      knowledge, until now, on how maternal malnutrition affects GnRH expression and
      estradiol serum concentrations of weaned pups. Six pregnant Wistar rats were
      separated into three groups at delivery with 6 pups each: control group (C) with
      free access to a standard diet containing 23% protein; protein energy restricted
      group (PER) with free access to an isoenergy and 8% protein diet; and an energy
      restricted (ER) group receiving a standard diet in restricted quantities, which
      were calculated according to the mean ingestion of the PER group. At 21 days post
      partum, the animals were killed and the serum estradiol was evaluated by
      radioimmunoassay. Immunohistochemistry for GNRH was performed. The serum
      estradiol concentration was decreased in PER and ER groups compared with C (PER,
      34%; ER, 19%;P < 0.01) and the staining of GNRH was restricted to arcuate nucleus
      and median eminence in the control group while in PER and ER stained processes
      aligned with the third ventricle wall (periventricular nucleus) were present. In
      conclusion, our data reinforce the concept that the maternal nutritional state
      during lactation is critical for sexual maturation since maternal malnutrition
      resulted in a neuron migration delay evidenced by an altered GnRH expression
      profile, probably a consequence of low estradiol serum levels.

PMID- 20670471
TI  - Dopamine receptor alterations in female rats with diet-induced decreased brain
      docosahexaenoic acid (DHA): interactions with reproductive status.
AB  - Decreased tissue levels of n-3 (omega-3) fatty acids, particularly
      docosahexaenoic acid (DHA), are implicated in the etiologies of non-puerperal and
      postpartum depression. This study examined the effects of a diet-induced loss of
      brain DHA content and concurrent reproductive status on dopaminergic parameters
      in adult female Long-Evans rats. An alpha-linolenic acid-deficient diet and
      breeding protocols were used to produce virgin and parous female rats with
      cortical phospholipid DHA levels 20-22% lower than those fed a control diet
      containing adequate alpha-linolenic acid. Decreased brain DHA produced a
      significant main effect of decreased density of ventral striatal D(2)-like
      receptors. Virgin females with decreased DHA also exhibited higher density of
      D(1)-like receptors in the caudate nucleus than virgin females with normal DHA.
      These receptor alterations are similar to those found in several rodent models of
      depression, and are consistent with the proposed hypodopaminergic basis for
      anhedonia and motivational deficits in depression.

PMID- 20670473
TI  - Polymorphism of MTHFR C677T, serum vitamin levels and cognition in subjects with
      hyperhomocysteinemia in China.
AB  - Relationships between hyperhomocysteinemia (HHE) and neurodegenerative diseases
      have been widely studied. However, the impact of serum total homocysteine (tHcy)
      levels on cognitive function has not been confirmed. C677T polymorphisms in the
      5,10-methylenetetrahydrofolate reductase (MTHFR) gene have impacts on tHcy level;
      it is suspected to influence cognitive function, but only few investigations have
      assessed its effects on non-dementia adults and the results have been
      controversial. Moreover, there is no report about Chinese subjects. In the
      present study, we determined C677T/MTHFR genotype, serum tHcy concentration and
      cognition in 182 nondemented subjects aged 55-88 years to probe the associations
      between MTHFRC677T mutation, increased tHcy levels and decreased cognitive
      function in a northern city in China. A serum tHcy level > or = 16 micromol/l was
      deemed HHE. Cognitive function was assessed by the Mini Mental State Examination
      (MMSE) and Basic Cognitive Aptitude Tests (BCAT). Results showed that: (i)
      subjects with the T allele had higher serum tHcy levels than those without,
      especially in lower folate status; (ii) T allele and CT/TT genotype frequencies
      in subjects with HHE were higher than in non-HHE subjects (P < 0.05); and (iii)
      serum tHcy level was inversely related to total BCAT score (P < 0.05) but
      MTHFR677 C to T polymorphism had no association with it. Our results confirmed
      that the MTHFR 677 C to T mutation, especially in lower serum folate
      concentration status, results in the increase of serum tHcy levels which is bad
      for cognitive function and indicates that higher serum folate level is of benefit
      in keeping lower serum tHcy level and better cognitive function. The results
      provide some valuable clues for individualized nutrition intervention of HHE and
      cognition decline in the middle-aged and the elderly.

PMID- 20670474
TI  - Effect of anserine ingestion on hyperglycemia and the autonomic nerves in rats
      and humans.
AB  - Anserine and L-carnosine are similar dipeptides synthesized by muscles of
      vertebrates. The functional role of anserine is unknown, although previous
      studies showed hypoglycemic effects of carnosine through autonomic nerves. Thus,
      we evaluated the effects of anserine on blood glucose levels and the neural
      activities. Intraperitoneal administration of specific doses of anserine to
      hyperglycemic rats reduced hyperglycemia and plasma glucagon concentrations,
      whereas thioperamide eliminated the effects of anserine. Intraduodenal injection
      of 0.1 mg anserine to anesthetized rats after laparotomy suppressed sympathetic
      nerve activity and enhanced activity of the vagal gastric efferent. In addition,
      oral administration of anserine reduced blood glucose levels during oral glucose
      tolerance testing in humans. These results suggest the possibility that anserine
      might be a control factor for the blood glucose, and that histaminergic nerves
      may be involved in the hypoglycemic effects of anserine.

PMID- 20670475
TI  - Early malnutrition diffusely affects children contrast sensitivity to sine-wave
      gratings of different spatial frequencies.
AB  - Cognitive, behavioral and neurophysiological deficits, associated with
      malnutrition, are described in the literature. The aim of this study was to
      evaluate the visual contrast sensitivity in children with early malnutrition,
      classified according to the anthropometric parameters of Waterlow. Visual
      contrast sensitivity of 16 boys from 7-10 years old was measured using the
      staircase psychophysical method, using vertical sine-wave gratings of 0.25, 1.0,
      2.0 and 8.0 cycles per degree (cpd) of visual angle. Malnourished children were
      approximately 3.3, 10.9 and 6.6 times less sensitive to the frequencies of 0.25,
      1.0 and 2.0 cpd, respectively, although they were approximately 1.1 times more
      sensitive to the frequency of 8.0 cpd. It is likely that early malnutrition
      adversely affected the magnocellular pathway on the one hand, since early
      malnourished children needed more contrast to detect low and low-to-medium
      frequencies; on the other hand, early malnutrition did not affect the
      parvocellular pathway, since there was an increase of sensitivity to the highest
      frequency.

PMID- 20670476
TI  - Impact of JAK2V617F mutation on thrombosis and myeloid transformation in
      essential thrombocythemia: a multivariate analysis by Cox regression in 141
      patients.
AB  - OBJECTIVE: To perform a multivariate analysis by Cox proportional hazard model of
      the impact of JAK2 V617F mutation on thrombosis and myeloid transformations in
      patients with essential thrombocythemia (ET). PATIENTS AND METHODS: The
      clinicopathologic features and outcome of a cohort of Chinese ET patients were
      retrospectively reviewed. JAK2 V617F mutation was detected by allele-specific
      polymerase chain reaction. Potential risk factors including JAK2 V617F that might
      impact on thrombosis and outcome were studied by multivariate analysis with Cox
      proportional hazard model. RESULTS: Of 141 patients studied, JAK2 V617F was found
      in 80 cases (57%). JAK2 V617F was positively correlated with hemoglobin and
      leukocyte count at diagnosis. Univariate analysis showed significant thrombotic
      risks to be JAK2 V617F (P=0.006), hemoglobin >13 g/dl (P=0.015), and age >55
      years (P=0.011). However, in multivariate analysis, only age and hemoglobin were
      independent risk factors. JAK2 V617F was unrelated to survival or
      leukemic/myelofibrotic transformation. CONCLUSION: In Chinese patients with ET,
      JAK2 V617F was positively associated with age, hemoglobin, and leukocyte count,
      but was not an independent risk for thrombosis.

PMID- 20670477
TI  - Identification of new markers discriminating between myeloid and lymphoid acute
      leukemia.
AB  - BACKGROUND: The heterogeneity of acute myeloid leukemia (AML) with respect to
      biology and clinical course resides in the fact that patients belonging to the
      same group show marked differences in their response to chemotherapy,
      necessitating a refinement of AML classification. METHODS: In order to define
      molecular markers for AML, we performed microarray analysis on peripheral blood
      cells from two M5 AML patients, and selected four differentially expressed genes
      to validate their expression by real-time quantitative PCR (RT-PCR). RESULTS: We
      have shown that two downregulated genes in AML, those encoding guanine nucleotide
      binding protein gamma11 (GNG11) and amphiregulin (AREG), are also downregulated
      in B-lineage acute lymphoblastic leukemia (B-ALL) and T-lineage acute
      lymphoblastic leukemia (T-ALL) patients. A second gene, that encoding
      ceruloplasmin (CP), is upregulated in AML but not in B-ALL and T-ALL. The level
      of expression of these genes varies from one patient to another. CONCLUSION:
      Since the number of patients studied is limited, further studies are needed with
      a larger series of patients to evaluate the potential utility of GNG11, AREG and
      CP as molecular markers for AML subtype classification. Our study is the first to
      analyze these genes in AML, B-ALL, T-ALL and chronic leukemia (myeloid and
      lymphoid) patients by RT-PCR. This rapid and sensitive method could be used to
      screen these genes in different types of leukemia.

PMID- 20670478
TI  - Treatment of acute promyelocytic leukemia with PETHEMA LPA 99 protocol: a
      Tunisian single center experience.
AB  - Acute promyelocytic leukemia (APL) has now become the most curable of all
      subtypes of acute myeloid leukemia. A cure rate of 75-80% can be anticipated with
      a combination of all-trans retinoic acid (ATRA) and anthracyclines. In Tunisia,
      the ATRA era began in 1998 with the use, consecutively, of two regimens of a
      combination of ATRA with anthracycline and cytarabine (APL93), and without
      cytarabine (LPA99). From 2004, 39 patients with confirmed APL either by t(15;17)
      or PML/RARA were treated by the PETHEMA LPA 99 trial. The rationale of this
      protocol by avoiding cytarabine is to reduce death in complete remission (CR)
      without increasing the incidence of relapse. Thirty-three patients achieved CR
      (84.6%). The remaining six patients were considered as failure due to early
      death: three caused by differentiation syndrome (DS) and three died from central
      nervous system hemorrhage. Baseline blood cell count (WBC) >10 x 10(9)/l (P=0.26)
      and creatinine >1.4 mg/dl (P=0.42) were not predictive of mortality. DS was
      observed in 11 patients (30.5%) with a median onset time of 12 days (range: 3-23
      days) and median WBC of 29 x 10(9)/L (range: 1.2 x 10(9)-82.7 x 10(9)/l). DS was
      severe in seven cases, moderate in four, and fatal in three cases. Body mass
      index > or =30 (P=0.044) and baseline WBC > or =20 x 10(9)/l (P=0.025) are
      independent predictors of DS. The median follow-up of this study is 36 months.
      Thirty patients are alive in continuous complete remission; two patients died in
      CR from septic shock and secondary myelodysplastic syndrome respectively; one
      patient died 47 months after achieving two relapses. Event free survival from
      diagnosis was 80% and overall survival was 82%. Our results are quite acceptable
      and can be improved by reducing mortality rate.

PMID- 20670479
TI  - Angiopoietin-2 mRNA expression is increased in chronic lymphocytic leukemia
      patients with poor prognostic features.
AB  - Several studies have demonstrated the potential prognostic importance of
      angiogenesis in chronic lymphocytic leukemia (CLL). Elevated expression of
      angiopoietin-2 (Ang-2), an angiogenic cytokine, was recently reported in CLL.
      However, data regarding prognostic significance of Ang-2 in CLL are limited.
      Therefore, we quantitated Ang-2 mRNA in purified mononuclear cells of 33
      untreated CLL patients and compared the transcript levels to traditional as well
      as modern prognostic factors in patients with CLL (clinical stage, disease
      course, IgVH mutation status, CD38, and ZAP-70 expression). Elevated Ang-2 mRNA
      concentrations were detected in 12 cases; 21 patients had very low or
      undetectable levels of Ang-2 transcript. There was significant association
      between high Ang-2 mRNA levels and unmutated IgVH genes (n=27, P=0.010) and with
      CD38 expression (n=32, P=0.011), but not with ZAP-70 expression (n=32, P=0.784),
      Rai stage (n=33, P=0.305) or stable versus progressive clinical course (n=33,
      P=0.443). There was a trend towards shorter progression-free survival in patients
      with high Ang-2 expression; however, it did not reach statistical significance
      (P=0.090). Our pilot data show that Ang-2 mRNA is differentially expressed in
      patients with CLL and its increased expression appears to be associated with poor
      prognostic features. Further studies are needed to confirm the results in a
      larger patient cohort.

PMID- 20670480
TI  - Anti-miR-21 oligonucleotide enhances chemosensitivity of leukemic HL60 cells to
      arabinosylcytosine by inducing apoptosis.
AB  - Drug insensitivity or resistance is a major obstacle for successful treatment of
      acute myeloid leukemia. MicroRNAs (miRNAs) are small non-coding RNA molecules.
      Increasing evidence suggests that miRNAs modulate cellular sensitivity to
      anticancer drugs. We used a specific anti-miR-21 oligonucleotide (AMO-miR-21) to
      sensitize leukemic HL60 cells to arabinosylcytosine (Ara-C) by down-regulating
      miR-21. AMO-miR-21 alone effectively inhibited HL60 cell viability as measured by
      MTT assays and induced apoptosis as evaluated by flow cytometry, whereas AMO-miR
      21 in combination with Ara-C enhanced HL60 cells to Ara-C-sensitivity and
      promoted Ara-C-induced apoptosis. Levels of miR-21 and its target PDCD4,
      quantified by real-time PCR, showed that expression of miR-21 was significantly
      decreased after AMO-miR-21 treatment. PDCD4 as a direct target of miR-21 in
      leukemic HL60 cells was confirmed by the dual-luciferase reporter assay. Our
      study suggests that AMO-miR-21 significantly sensitizes HL60 cells to Ara-C by
      inducing apoptosis and these effects of AMO-miR-21 may be partially due to its up
      regulation of PDCD4. Therefore, exploiting synergistic effects between AMO-miR-21
      and Ara-C might be an effective clinical strategy for leukemia chemotherapy.

PMID- 20670481
TI  - Early infections in patients undergoing high-dose treatment with stem cell
      support: a comparison of patients with non-Hodgkin lymphoma and multiple myeloma.
AB  - BACKGROUND: Infections are life-threatening complications in patients undergoing
      high-dose chemotherapy with stem cell support (HDT). Knowledge of the infectious
      pathogens is essential to make a safe outpatient setting. METHODS: We conducted a
      retrospective study of 208 patients treated with HDT. The population included non
      Hodgkin lymphoma (NHL) and multiple myeloma (MM) patients. No patients received
      prophylactic antibacterial treatment. RESULTS: Pathogens were isolated from 44%
      of all patients. MM patients more frequently had multiple pathogens in blood
      cultures (38% versus 25%). Transplantation related mortality was similar between
      the groups. CONCLUSION: The frequency of isolated pathogens, positive blood
      cultures, and the diversity of pathogens were higher in MM patients as compared
      to NHL patients. However, this did not translate into higher transplantation
      related mortality, probably because broad-spectrum antibiotic treatment could be
      initiated immediately. A safe outpatient setting with prophylactic antibiotic
      treatment is dependent on continuous collection and registration of
      microbiological findings.

PMID- 20670482
TI  - Gene expression profiling of CD3gamma, delta, epsilon, and zeta chains in CD4(+)
      and CD8(+) T cells from human umbilical cord blood.
AB  - In order to elucidate the feature of T-cell immune status in umbilical cord blood
      (CB) from humans, the expression levels of CD3gamma, delta, epsilon, and zeta
      chain genes in CD4(+) and CD8(+) T cells of CB were analysed by real-time PCR.
      CD4(+) and CD8(+) T cells sorted from 12 cases of CB and 10 peripheral blood (PB)
      samples from healthy adults were used in the study. The beta2-microglobulin gene
      was used as an endogenous reference, and the evaluations of mRNA expression level
      of each CD3 gene were used by the 2(-DeltaC(t)) x 100% method. In CD4(+) T cells,
      the expression levels of CD3gamma, delta, and zeta genes (16.54+/-6.49, 3.53+/
      1.15, and 5.48+/-1.10%) from CB were significantly higher than those from PB
      (P=0.001, P=0.017, and P=0.000, respectively). Higher expression levels of
      CD3delta and zeta genes (3.43+/-1.19 and 5.24+/-1.42%) in CD8(+) T cells from CB
      were found than those from PB (P=0.000 and P=0.004). Moreover, the expression
      level of CD3epsilon gene in CD4(+) T cells from CB (13.29+/-5.72%) was
      significantly different from that in CD8(+) T cells (7.81+/-4.72%, P=0.018).
      Thus, the expression pattern of four CD3 genes were gamma>epsilon>zeta>delta in
      both CD4(+) and CD8(+) T cells from CB, while similar expression pattern was
      found in CD8(+) T cells from PB samples. In contrast, the expression pattern was
      presented as epsilon>gamma>zeta>delta in CD4(+) T cells from PB. In conclusion,
      the present study characterized the expression pattern of CD3gamma, delta,
      epsilon, and zeta chain genes in CD4(+) and CD8(+) T cells from CB, which might
      be very useful for further understanding the feature of T-cell immune status in
      umbilical cord blood. Higher expression of CD3 genes in CD4(+) T cells might
      relate to the strong ability of activation of TCR-mediated signals, and suggests
      that this is one of the features responsible for the low allo-reactivity of CB T
      cells.

PMID- 20670483
TI  - Erythrocyte membrane defects and asymmetry in paroxysmal nocturnal hemoglobinuria
      and myelodysplastic syndrome.
AB  - Paroxysmal nocturnal hemoglobinuria (PNH) and myelodysplastic syndromes (MDS) are
      clonal disorder of haematopoietic stem cells that may eventually lead to chronic
      anemia. The ultrastructural defects in erythrocyte membranes may have a role in
      early red cell destruction within circulation. The lifespan of the erythrocyte
      primarily correlates to externalization of phosphatidylserine (PS) and loss of
      glycophorins from the erythrocyte surface. The span of survival of mature
      erythrocytes in the circulation in case of MDS and PNH is yet unclear and has
      been studied by measuring simultaneous exposure of PS and loss of
      glycoconjugates, primarily glycophorins from membrane surface. The extent of the
      loss of PS asymmetry and cell surface glycophorins in density separated
      erythrocytes of six MDS and three PNH patients has been probed by fluorochrome
      conjugated annexin V and wheat germ agglutinin using flow cytometry. The cells
      with lighter density showed a higher amount of PS on the outer surface compared
      to those of heavier cells in all PNH and MDS cases, showing the opposite trend to
      that observed in normal erythrocytes. In addition, the lighter cells had more
      cell surface glycophorins compared to heavier cells in all the cases. Such
      lowering of glycophorin levels from the lighter to heavier cells was maximum in
      refractory anaemia (RA) and minimum in the normal cells studied. Greater loss of
      PS asymmetry and cell surface glycophorin in the lighter or younger erythrocytes
      together could be responsible for their faster destruction and removal
      (eryptosis) in PNH and MDS.

PMID- 20670485
TI  - Obituary. Sven-ivar seldinger.

PMID- 20670484
TI  - Hepatitus B virus reactivation in HBV-DNA negative and positive patients with
      hematological malignancies.
AB  - Reactivation of hepatitis B virus (HBV) is a frequent complication of
      chemotherapy (CT) in patients with HBsAg carriers. In this prospective study, we
      documented CT induced HBV reactivation risk in patients with hematological
      malignancies. HBV reactivation risk is influenced by baseline viral load.
      Therefore, we divided our study population into two groups according to HBV-DNA
      status. HBV-DNA negative patients (n=18) were treated with nucleoside analogues
      once HBV reactivation was observed. HBV-DNA positive patients (n=12) commenced
      lamivudine before the initiation of the CT. In HBV-DNA negative patients HBV
      reactivation was found in 10 patients (55.5%). HBV reactivation was significantly
      more frequent in chronic lymphocytic leukemia (CLL) patients (P=0.008) and in
      patients receiving rituximab containing chemotherapy regimens (P=0.06). Eight
      patients (80.0%) responded to antiviral treatment after HBV reactivation. Two CLL
      patients experienced a flare-up after the withdrawal of antiviral therapy. In HBV
      DNA positive patients, HBV reactivation was observed in four patients (33.3%)
      during lamivudine treatment and in two patients after lamivudine withdrawal. This
      study demonstrated the increased risk of CT-induced HBV reactivation in CLL
      patients, for the first time.

PMID- 20670486
TI  - An experimental and angiographic explanation of why ulcerated carotid bulbs
      embolize.
AB  - SUMMARY: The flow dynamics and pressure relationships in an ulcerated
      atherosclerotic carotid bulb obtained at post-mortem were studied and correlated
      with angiographic findings in a similar live patient. Using the lost wax
      technique, we created replicas of an ulcerated atherosclerotic carotid bulb from
      a fresh cadaver, and placed those replicas in a circuit of pulsating non
      Newtonian fluid. Flow profiles were adjusted to replicate human physiologic
      flows, and flow rates of 400, 600, and 800 milliliters per minute were evaluated.
      In the replicas, the slipstreams were opacified with isobaric dyes, and images
      were recorded both on 35 mm film and on SuperVHS high speed video. Data were
      collected from needles placed radially in the common carotid artery, in the
      region of the maximal atherosclerotic narrowing, and in the internal carotid
      artery. Though pressure relationships could not be obtained in the live human for
      ethical reasons, angiography in a similar stenosis was evaluated for slipstream
      dynamics. The post-mortem replica had a 55% diameter stenosis (88% area stenosis)
      of the carotid bulb with a shallow 3 mm ulcer. Flow in the common carotid artery
      showed undisturbed slipstreams, but as these slipstreams entered the narrow bulb,
      they crowded together, accelerating dramatically, with a jet continuing distally
      beyond the maximal narrowing for at least 2 vessel diameters, where flow again
      became normal. As fluid entered the narrowed bulb, radial pressures decreased and
      within the ulcer a vortex circulation was found. Similar findings were observed
      on the angiographic images of the live patient. This combination of events, the
      slowly swirling fluid in the ulcer, which would allow platelet aggregates to
      form, and the intermittent low pressure of the Bernoulli effect which could pull
      the aggregates into the adjacent rapidly flowing blood may help explain how
      ulcerated carotid plaques lead to embolic stroke.

PMID- 20670487
TI  - Stereotactic Transcerebellar Approach to Pontine Lesions through the Middle
      Cerebellar Peduncle.
AB  - SUMMARY: A stereotactic approach to the pons through the middle cerebellar
      peduncle based on MR studies was used to biopsy 18 patients. The stereotactic
      coordinates and angles were defined with reference to three orthogonal planes
      (midsagittal, IVth ventricular floor and pontomedullary junction). The
      pathological diagnoses were in keeping with clinical outcome and comprised five
      highgrade astrocytomas, three low-grade astrocytomas, two glioblastomas
      multiforme, two oligodendrogliomas, two primitive neuroectodermic tumours, two
      lymphomas, one medulloblastoma, and one tuberculosis. This approach provides a
      high yield of positive histological diagnoses with little morbidity (transient
      neurological deficits in two cases) and thereby avoids inappropriate therapy.

PMID- 20670488
TI  - Multifocal and metameric spinal cord arteriovenous malformations. Review of 19
      cases.
AB  - SUMMARY: We describe 19 (16.0%) multiple vascular malformations (AVMs) in 119
      spinal cord arteriovenous malformations (SCAVMs). The associated lesions were
      eight vertebral vascular malformations, two cutaneous, four limbs, four radicular
      AVMs, three bifocal SCAVMs; one patient had a bifocal cord lesion associated with
      vertebral and limb localisations. Various syndromic associations were seen: nine
      Cobb, two Klippel-Trenaunay-Weber, one Parkes Weber. An additional subgroup of
      unclassified associations is constituted by seven cases with bifocal intradural
      uni or multimetameric lesions. In our SCAVMs series, the incidence ofmultipie
      vascular lesions is high, in particular multifocal intradural malformations.
      Metameric distribution is the most frequent type of multiplicity. Identification
      of the myelomeric level involved in SCAVM allows segmental link between various
      lesions of mesodermal or neural crest origin to be discussed.

PMID- 20670489
TI  - Cost-effectiveness of percutaneous automated lumbar nucleotomy. Comparison with
      traditional macro-procedure discectomy.
AB  - SUMMARY: This study was conducted in order to evaluate the cost-effectiveness of
      percutaneous automated lumbar nucleotomy in comparison with traditional macro
      procedure discectomy in the treatment of herniated discs. Sixty-eight patients
      undergoing surgical procedures and 90 treated with nucleotomy were consecutively
      included. Both cohorts were assessed pre-operatively and at regular intervals for
      one year or more after treatment by independent observers, using a clinical
      overall scoring system (COS) with 0 being the best attainable result and 1000 the
      poorest conceivable status of the patients. There were better clinical results
      after surgery with 78% successes after one year compared to 62% after nucleotomy.
      By including subsequent operations and re-operations after failure to respond to
      the primary treatment, the success rates rose to 79% and 77%, respectively. The
      cost of surgical treatment was calculated to USD 6.119 per patient and the cost
      of a nucleotomy procedure was USD 1.252. Owing to an almost five times higher
      price of surgery than nucleotomy, the latter turned out to be 2.7 to 3.9 times
      more cost-effective, depending on whether secondary treatment was included or
      not. Due to the minimal difference in final outcome between the groups, however,
      the marginal cost per extra success in patients primarily treated with surgery
      was as high as USD 205.850. The study concludes that nucleotomy, as a mini
      invasive procedure with low complication rates and the potential of a quick
      recovery, is more cost-effective than traditional surgical treatment for lumbar
      disc herniation.

PMID- 20670490
TI  - Staged endovascular management of a ruptured intracranial aneurysm.
AB  - SUMMARY: The goal of treatment of ruptured intracranial aneurysms is the
      exclusion of the aneurysm from the intracranial circulation. Recently
      endovascular techniques have provided an alternative to open surgery in selected
      patients. Herein, we present a patient who underwent staged endovascular
      procedures to achieve definitive treatment of an intracranial fusiform vertebral
      artery aneurysm. Definitive immediate therapy for the aneurysm was not possible
      at first presentation because of the aneurysm location and configuration, and
      because of absence of collateral circulation. The first stage involved coiling a
      daughter bleb suspected of being the source of haemorrhage. This provided acute
      protection against rebleeding without sacrificing the parent artery. The second
      and more definitive stage, delayed for 31 days, involved balloon occlusion of a
      fusiform aneurysm by sacrificing the parent vessel.

PMID- 20670491
TI  - Treatment of a Giant Aneurysm of the Right Middle Cerebral Artery with GDCs after
      Extracranial to Intracranial Bypass. A Technical Case Report.
AB  - SUMMARY: A case of a giant aneurysm of the right middle cerebral artery treated
      with Guglielmi detachable coils is reported. Extracranial to intracranial bypass
      had previously been performed and surgical trapping had been attempted. During
      the endovascular procedure, balloon test occlusion of the middle cerebral artery
      was performed in order to demonstrate clinical and angiographic tolerance to
      parent vessel occlusion. A previous occlusion test in the right common carotid
      artery did not show sufficient flow through the bypass to perform safe parent
      vessel occlusion. Diagnostic imaging, the endovascular procedure, and
      haemodynamic aspects in cases in which parent vessel occlusion is required after
      extracranial-intracranial bypass are described and the literature is reviewed.

PMID- 20670492
TI  - Endovascular Management of a Traumatic Basilar Tip Aneurysm following Endoscopic
      Ventriculostomy in a Child.
AB  - SUMMARY: We report the case of four year nine month old girl that presented a
      basilar tip iatrogenic arterial aneurysm following ventriculostomy. Despite being
      a false aneurysm the lesion was successfully coiled two years later.

PMID- 20670493
TI  - Spinal cord infarction complicating embolisation of vertebral metastasis: a
      result of masking of a spinal artery by a high-flow lesion.
AB  - SUMMARY: A 70-year-old woman presented with severe back pain secondary to
      metastasis of renal cell carcinoma to the second lumbar vertebral body. She had
      no evidence of spinal cord compression clinically or on MR imaging. Tumour
      embolisation was performed for pain relief The embolisation was complicated by
      spinal cord infarction resulting from angiographic masking of a spinal artery by
      diversion of contrast material into the high-flow tumour.

PMID- 20670494
TI  - Improvement of Functional Magnetic Resonance Imaging by a Novel Fibre-optic
      Device and 3D Software.
AB  - SUMMARY: This report describes three years of clinical experience with a new set
      of devices aimed at improving functional MRI of speech areas. They provide a
      valuable tool for pre-operative definition of hemispheric localization and
      spatial extension of these areas, especially in left-handed persons. The fibre
      optic device described here transmits stimuli for cognitive tasks to patients
      undergoing MR investigations. Cognitive tasks elicit a defined brain activity
      lasting for several minutes. The resultant metabolic changes are detectable by
      functional MRI. The software (FIT ware) applied to process raw data allows semi
      automated segmentation of the brain so as to obtain 3D images. Furthermore it
      allows the superposition of functional data. The effectiveness of the equipment
      was assessed on the basis of data from 140 fMRI studies. Intra-operative
      verification in eight patients with tumours located in the speech areas showed
      that the new set-up identified the speech-dominant side in each case and located
      speech areas in accordance with electrophysiological procedures.

PMID- 20670495
TI  - Opinion. Comment on the article "unruptured intracranial aneurysms - risk of
      rupture and risks of surgical intervention". The new England journal of medicine
      339: 24, 1725-1733, 1998.

PMID- 20670496
TI  - Erratum. Endovascular management of a major vascular complication after
      orthognatic surgery.
AB  - SUMMARY: We describe the effective endovascular management of a severe
      haemorrhagic complication in a 24 year old man which could not be controlled by
      surgical means. Major bleeding caused by bilateral injured internal maxillary
      arteries after orthognatic surgery occurred. Angiography proved to be efficient
      in exactly localizing the bleeding sites while endovascular occlusion ultimately
      stopped the bleeding in a life-threatening situation for the patient.

PMID- 20670497
TI  - To the editor. Corrosion of tungsten spirals.

PMID- 20670498
TI  - To the Editor. South American Working Group in Interventional and Therapeutic
      Neuroradiology (SAWITN).

PMID- 20670499
TI  - Editorial. From aneurysms to aneurysmal vasculopathies.

PMID- 20670500
TI  - Chinese experience in endovascular management of spinal cord vascular
      malformations.

PMID- 20670501
TI  - Time of Flight 3D Magnetic Resonance Angiography in the Follow-up of Coiled
      Cerebral Aneurysms.
AB  - SUMMARY: The use of Guglielmi Detachable Coil (GDC) for the en do vascular
      treatment of intracerebral aneurysms is increasing, particularly in those
      aneurysms for which there is a high surgical morbidity and mortality. However,
      the long-term efficacy of GDC is not known. Until the natural history of GDC
      treatment is established longterm follow-up in this cohort of patients is
      required, of necessity involving repeated intraarterial angiography (IA DSA) with
      its known attendant risks and exposure to ionising radiation. Three dimensional
      time-of-flight magnetic resonance angiography (3D TOF MRA) is now readily
      accepted as a non-invasive screening tool for familial aneurysmal disease and has
      been used as an alternative to IA DSA in the surgical management of aneurysmal
      subarachnoid haemorrhage. MRA in patients treated with GDC is safe, imparts no
      radiation dose and provides acceptable image quality. The aim of this study was
      to assess 3D TOP MRA source data, maximum intensity projection (MIP) and 3D
      isosurface reconstruction in comparison to IA DSA in the follow-up of 25 patients
      treated with GDC. Images were assessed for parent and branch artery flow, the
      presence of neck recurrence and aneurysm regrowth. There was good correlation for
      all these features when 3D isosurface MRA and source data were compared with IA
      DSA. The correlation between MIP MRA and IA DSA was less robust. Additional
      confidence can be obtained by performing plain films of the skull to demonstrate
      change in coil ball configuration. MRA has the potential to replace IA DSA in the
      follow- up of GDC treated cerebral aneurysms.

PMID- 20670502
TI  - Pressure Measurements across Vascular Stenoses. Practice and Pitfalls.
AB  - SUMMARY: We describe and analyze pressure measurements across vascular stenoses
      in an atherosclerotic human carotid bulb replica using catheters of different
      diameters. Replicas of an atherosclerotic human carotid bulb were created using
      the lost wax technique, and were placed in a circuit of pulsating nonnewtonian
      fluid. Flows were adjusted to replicate human physiologic flow profiles. Common
      carotid artery total flow volume of 600 milliliters/minute was studied. A
      pressure recording device was calibrated; data were received from catheters
      placed longitudinally in the common carotid artery and internal carotid artery.
      The internal carotid artery pressures were obtained both through the stenosis as
      is usually performed in the angiography suite and through the vessel side-wall
      beyond the stenosis as a control. Internal carotid artery flow volumes were also
      measured with and without the catheter through the stenosis. Multiple pressure
      recordings and volume measurements were obtained in the replica using 7 French, 5
      French, and 2.5 French catheters. Measurements of the replica showed a 58%
      diameter stenosis and an 89% area stenosis of the carotid bulb. All longitudinal
      pressure measurements in the common carotid artery agreed with control values
      regardless of the diameter of the catheter used. Pressure measurements were also
      in agreement with control values in the internal carotid artery using the 2.5
      French catheter. However, when larger diameter catheters were employed, pressures
      measured with the catheter through the stenosis fell when compared to control
      values. Additionally, internal carotid artery flow volumes were also decreased
      when the larger diameter catheters were placed across the stenosis. Large
      diameter catheters when placed across vascular stenoses may cause an occlusive or
      near-occlusive state and artifactually increase the measured transstenotic
      vascular pressure gradient as well as decrease forward vascular flow.

PMID- 20670503
TI  - The role of controlled anticoagulation in balloon occluding vertebral arteries to
      treat giant fusiform aneurysms of the basilar artery.
AB  - SUMMARY: We suggest and discuss the role of controlled anticoagulation therapy
      after the balloon occlusion of vertebral arteries to treat giant fusiform
      aneurysms in the basilar trunk. Two cases of giant fusiform aneurysms were
      treated with balloon occlusion of vertebral arteries. Both of these patients
      suffered severe brain stem ischaemia. Anticoagulants were used to adjust the PTT
      to 1.5-2.5 times the normal level to control the formation speed of thrombosis
      inside the aneurysms. Case 1 was obliged to suspend the anticoagulation therapy
      one week after occlusion because of digestive tract haemorrhage, and died of
      severe brain stem ischaemia. On autopsy, the sac of the aneurysm was totally
      occupied by the thrombus. Two perforating arteries feeding the brain stem arising
      from the wall of the aneurysm and infarction in the brain stem were found. Case 2
      was anticoagulated strictly and progressively improved after three weeks.
      Anticoagulation was terminated after one month. Follow-up MRI showed the aneurysm
      had disappeared six months later. Giant fusiform aneurysms in the basilar artery
      trunk can be treated with the balloon occlusion of vertebral arteries which
      induces thrombosis in the sac of aneurysm. Controlled anticoagulation should be
      given to slow down the thrombotic obliteration in the perforators arising from
      the aneurysm wall to the brain stem and give the brain stem have enough time to
      establish the sufficient collateral circulation.

PMID- 20670504
TI  - Multifocal cerebral fusiform aneurysms in children with immune deficiencies
      report of four cases.
AB  - SUMMARY: We describe three children infected by the human immunodeficiency virus
      (HIV 1), and one child suffering from familial mucocutaneous candidiasis, who all
      had multiple, fusiform subarachnoid intracranial aneurysms. Because infectious
      causative agents were never detected at the level of the lesions, a classical
      "mycotic" origin of these aneurysms seemed unlikely. Despite the fact that these
      aneurysms have the same angiographic appearance, they have different etiologies
      (immune and infectious). These data open the discussion on the reciprocal role of
      an infectious or immune initial trigger acting on a vascular (endothelial)
      target. The specificities of the target in terms of location and response enhance
      specific topographic characteristics (phenotypes) of the cerebral vasculature.

PMID- 20670505
TI  - Endarterectomy of an Occluded ICA: Short Segment Occlusion with Distal Patency
      Maintained by an Aberrant Ascending Pharyngeal Artery.
AB  - SUMMARY: The authors report a case in which an anomalous ascending pharyngeal
      artery maintained patency of the internal carotid artery beyond an occlusion. The
      patient presented with ipsilateral transient ischaemic attacks and was found to
      have an internal carotid artery occlusion on Doppler ultrasound. Subsequent
      angiography demonstrated retrograde flow in the ipsilateral APA, perfused by
      pharyngeal anastomoses from the contralateral APA with slow antegrade flow in the
      ipsilateral ICA distal to the occlusion. Carotid endarterectomy resulted in
      abolition of the TIA's.

PMID- 20670506
TI  - Endovascular management of complete vertebral artery dissection presenting with
      subarachnoid haemorrhage.
AB  - SUMMARY: Spontaneous vertebral artery (VA) dissection may involve the intradural
      segment of the VA and result in subarachnoid haemorrhage (SAH). These lesions are
      frequently associated with recurrent SAH, and have a high mortality. Prior to the
      development of endovascular techniques the majority of these lesions were treated
      surgically. In cases where the dissection involved the posterior inferior
      cerebellar artery (PICA) origin surgery was associated with significant
      complications including recurrent SAH from retrograde VA flow into the dissected
      segment above the surgical clip. We describe two cases of complete VA dissection
      in which the entire intradural VA was sacrificed to prevent recurrent SAH. The
      first case tolerated planned left PICA occlusion without developing a significant
      neurological deficit. The second case had infarcted the right PICA territory at
      presentation.

PMID- 20670507
TI  - Puncture of the superficial sylvian vein for embolisation of cavernous dural
      arteriovenous fistula.
AB  - SUMMARY: Dural arteriovenous fistulas (DAVF's) of the cavernous sinus are curable
      by endovascular means in the vast majority of cases. Both transarterial and
      transvenous approaches by femoral route can be used for closure. In rare cases
      with unsuitable anatomy or angioarchitecture, an endovascular approach is
      proposed by open surgical exposure of a major venous outflow, e.g. the superior
      ophthalmic vein. We report on a case of unsuccessful attempts at transarterial
      and transvenous catheter navigation through traditional endovascular routes,
      where surgical exposure of the major cortical venous drainage was necessary. A
      direct puncture of the sylvian vein allowed placement of a microcatheter in the
      cavernous sinus and occlusion of the fistula by coils.

PMID- 20670508
TI  - Treatment of a vertebral dissecting aneurysm with a balloon-expandable stent and
      guglielmi detachable coils.
AB  - SUMMARY: A 43-year-old man with dissecting vertebral artery aneurysm presented
      with subarachnoid haemorrhage. The vertebral angiography showed a fusiform
      dilatation at the right intracranial vertebral artery between the origin of
      posterior inferior cerebellar artery and the vertebral union. After failing
      conservative therapy, a balloon-expandable stent was placed at intracranial
      vertebral artery, in a manner such that the entire dissecting aneurysm was
      covered. On follow-up angiogram, we recognized regrowth of theresidual aneurysm
      and stent deformation. The parent artery was occluded completely with several
      Guglielmi detachable coils. Brainstem dysfunction or rebleeding of the aneurysm
      were not encountered. Recently stenting therapy was deployed for a patient with
      dissecting aneurysm of the extracranial carotid or vertebral artery who was not a
      candidate for surgical treatment. We discuss the feasibilities and limitations of
      stent therapy.

PMID- 20670509
TI  - Psychic stress as a trigger of the spontaneous development and rupture of an
      aneurysm? A case report.
AB  - SUMMARY: We present angiographical and neuropathological data of a 51-year-old
      woman, who primarily suffered from a recurrent glomus temporale tumour on the
      left side and who finally died after a spontaneous rupture of a distal basilar
      aneurysm which developed during angiography. As a second important finding the
      existence of a vasospasm at the time of the rupture is also confirmed.

PMID- 20670510
TI  - Superselective Intra-arterial Thrombolysis for Acute Cardioembolic Stroke in a
      Child with Idiopathic Dilated Cardiomyopathy. A Case Report.
AB  - SUMMARY: We describe a case of cardioembolic dominant hemisphere internal carotid
      artery occlusion in a child with idiopathic dilated cardiomyopathy. The patient
      was subjected to superselective local intra-arterial thrombolysis using
      recombinant tissue plasminogen activator (A lteplase; Actilyse((R))). In presence
      of good collateral flow local intra-arterial thrombolysis prevented a major
      dominant hemisphere ischaemic stroke, although post-interventional computed
      tomographic scans disclosed haemorrhagic conversion in the left corpus striatum.
      Forty eight months after ischaemic stroke and thrombolysis the patient is
      ambulatory with a moderate neurologic deficit.

PMID- 20670511
TI  - Endovascular Retrograde Cortical Venous Approach to Disconnect Retrograde
      Leptomeningeal Venous Reflux in a Patient with Dural AVF.
AB  - SUMMARY: We report a case of dural arteriovenous fistual (DAVF) with cortical
      venous reflux in whom disconnection of the refluxing cortical vein was achieved
      by using a retrograde transcortical venous approach through the cortical vein
      itself.

PMID- 20670512
TI  - Digital subtraction and conventional blood flow studies in porcine experimental
      aneurysms.
AB  - SUMMARY: Flow studies are important to understanding pathogenesis and treatment
      of cerebral aneurysms, but have not been possible in the clinical setting. We
      used experimental aneurysms established in and then removed from pigs to compare
      and correlate flow studies by high-speed video photography of introduced
      particles and by clinically applicable digital subtraction angiography. Venous
      pouches were used to create aneurysms in incised common carotid arteries. After
      aneurysms and parent arteries were removed, specimens were rendered translucent
      with solvents so they could be studied by video photography of introduced plastic
      particles in addition to digital subtraction angiography with iodinated contrast
      material. Regions of interest were studied individually. Mean transit time for
      contrast in the preparation correlated with videographically measured particle
      flow velocity (r = 0.616). Digital subtraction angiography should be useful in
      evaluation of flow in the clinical assessment and treatment of cerebral
      aneurysms, such as in endovascular therapy.

PMID- 20670513
TI  - Experimental pseudo arteriovenous malformation. A model for training and
      research.
AB  - SUMMARY: There are few experimental models of arteriovenous malformations (AVM).
      The following study was designed to evaluate an easy-to-perform method in a
      canine model. Bilateral high-flow carotid to external jugular vein arteriovenous
      fistulae (AVF) were created in three adult dogs. 21 days after surgery one AVF
      was occluded by a coated stent, whereas the contralateral side remained patent.
      Frequent angiograms of the carotid and the vertebral arteries were performed in
      the nine months after surgery to investigate the effects of long-standing high
      flow AVF. Because of a significant steal effect, the fistulae recruited arterial
      blood flow at a rapid rate from the ipsilateral vertebral artery and to lesser
      extent from the contralateral side, which was only disclosed after occlusion of
      the contralateral AVF. These cephalic pseudo AVMs were seen in all three dogs.
      The model presented is easy to establish and shows angioma-like morphological
      components comparable to human AVM. It is useful for the testing of new catheters
      and embolic materials as well as in the training of superselective navigation
      with micro catheters. However, it is unsuitable for examination of intracranial
      pathophysiology.

PMID- 20670514
TI  - Spontaneous vertebrovertebral arteriovenous fistulae clinical features,
      angioarchitecture and management of twelve patients.
AB  - SUMMARY: Spontaneous vertebrovertebral arteriovenous fistula (SVVAVF) is a rare
      condition which often presents as a bruit. We reviewed the clinical and imaging
      records of 12 patients with 13 SVVAVF fistulae who were managed at our
      institution over the last 14 years. Two patients had predisposing conditions,
      neurofibromatosis in one and Ehlers-Danlos syndrome in the other. Nine of the
      patients presented with a bruit; one patient presented with a myelopathy and one
      with congestive cardiac failure. Six of the 13 fistulae were at Cl and five of
      these six were children. 1n seven of the fistulae there was retrograde flow in
      the distal vertebral artery. Eight patients underwent endovascular treatment. Six
      required both contralateral and ipsilateral vertebral artery approaches. Coils
      (two patients), balloons (three patients), or a combination of agents including
      liquid adhesives (three patients) were used. Preservation of the vertebral artery
      was possible in three of the eight patients. Angiographic obliteration was
      obtained in all eight patients. There were no significant procedure-related
      complications. Embolisation is the primary treatment of SVV AVF and can be
      performed successfully with low morbidity. Preservation of the vertebral artery,
      although desired, is often not possible.

PMID- 20670515
TI  - Transvenous embolisation of spontaneous carotid-cavernous fistulas by sequential
      occlusion of the cavernous sinus.
AB  - SUMMARY: There are two important pathological features associated with carotid
      cavernous fistula (CCF): the retrograde cortical venous drainage that can cause
      intracranial haemorrhage and non haemorrhagic neurological deficit and the
      retrograde ophthalmic venous drainage that causes orbital venous congestion and
      visual impairment. We propose a sequential embolisation strategy by the selective
      occlusion of these two pathological features as the initial steps followed by
      occlusion of the rest of the cavernous sinus. Eight patients with spontaneous CCF
      were treated by transvenous embolisation using our embolisation strategy. The
      clinical features, angiographic findings, embolisation procedures, and clinical
      and angiographic outcomes were analyzed. The follow-up period ranged from one to
      21 months. Clinical cure was achieved in six patients at one to two month follow
      ups. One patient with bilateral CCFs had clinical cure of the right eye and
      clinical improvement of the left eye at three-month follow-up. Another patient
      had clinical cure at one-month follow-up except residual VI nerve palsy. Two
      patients had complete angiographic obliteration of the fistula immediately after
      the embolisation procedure. Another three patients underwent follow-up
      angiography at one to 16 months and all showed angiographic cure. There were no
      immediate or late complications. Our embolisation strategy offers a safe and
      effective option in the embolisation of spontaneous CCF as demonstrated by the
      clinical results of our eight patients.

PMID- 20670516
TI  - Extracavernous arteriovenous fistulae. Report of five cases.
AB  - SUMMARY: We report five cases of arteriovenous fistulae (AVFs) of the carotid
      system. Two were traumatic non penetrating injuries and involved the
      subarachnoid, extracavernous part of the intracranial internal carotid artery;
      two were spontaneous and involved the internal carotid artery in its extracranial
      portion; one was a spontaneous AVF of the ascending pharyngeal artery. All the
      symptoms due to these AVFs were not related to the location of the fistula, but
      to the congestive venous drainage. The revealing symptoms regressed and/or
      improved after transarterial detachable balloon embolisation that led to complete
      occlusion of the AVFs.

PMID- 20670517
TI  - Combined endovascular stenting and endosaccular coiling for the treatment of a
      wide-necked intracranial vertebral aneurysm. Technical case report.
AB  - SUMMARY: We describe a clinical case of the combined application of endovascular
      stent placement and GDCoils packing in the management of a ruptured wide necked
      intracranial aneurysm. A 27-year-old man had a subarachnoid haemorrhage secondary
      to the rupture of a large wide necked left vertebral aneurysm. This aneurysm was
      judged to be inoperable. A functional occlusion test failed because of poor
      collateral flow and combined stenting and coiling was used to occlude the
      aneurysm with preservation of the parent artery. A femoral approach was used. An
      18 mm long ACS((R)) Duet stent was placed across the base of aneurysm and
      expanded to 4 mm to act as a buttress. A microcatheter was then advanced through
      the stent mesh and GDC's were deposited for occlusion. This technique provides
      new possibilities for wide-necked intracranial aneurysms. Further studies are
      required on the mechanical and thrombogenic properties of stents and on the long
      term follow-up, but this technology may play a role in some cases of aneurysm
      treatment.

PMID- 20670518
TI  - Treatment of external carotid artery fistula by percutaneous venous approach.
AB  - SUMMARY: Endovascular treatment of high flow arteriovenous fistula following a
      stab wound injury in a 25 year old man is reported. Previously performed proximal
      embolisation and surgicalligation failed to occlude the fistula but resulted in
      changes to the normal vascular anatomy and significant clinical and cosmetic
      disturbances. A direct puncture of the draining vein was performed and the
      fistulous connection occluded by placement of detachable coils and deposition of
      glue. Follow-up showed disappearance of the AVF as well as complete clinical
      recovery.

PMID- 20670519
TI  - Acute histologic and ultrastructural study in one case of human basilar tip
      aneurysm embolised with guglielmi detachable coils.
AB  - SUMMARY: Histologic findings after Guglielmi detachable coils endovascular
      embolisation have been studied in experimental aneurysms. Few reports describe
      histopathologic reactions to platinum coils in humans. In this report we describe
      gross, light microscopic pathology and scanning electron microscopy study of a
      ruptured basilar tip artery aneurysm in a patient who died 16 hours following
      coiling.

PMID- 20670520
TI  - Letter to Editor. Separate Origin of the Left Internal and External Carotid
      Artery from the Aortic Arch associated with Contralateral Intracranial Giant
      Aneurysm.
AB  - SUMMARY: One of the rare anomalies of the common carotid artery is the separate
      origin of the internal and external carotid artery. We present the case of a
      patient who was admitted to hospital for cerebral angiography to exclude an
      intracranial aneurysm. The DSA revealed a giant aneurysm of the right internal
      carotid artery and separate origins of external and internal carotid arteries
      from the aortic arch. To our best knowledge no similar case has previously been
      reported.

PMID- 20670521
TI  - Letter to the editor.

PMID- 20670522
TI  - Letter to editor. Retrograde cortical transvenous route for dural arteriovenous
      fistulae.

PMID- 20670523
TI  - Editorial. Letter from the president: the world scientific conference of the
      world Federation of interventional and therapeutic neuroradiology. Vilamora,
      portugal-june 4-8, 1999.

PMID- 20670524
TI  - Editorial. Can and should radiology survive? "Chronicle of a death foretold".

PMID- 20670525
TI  - Correct use of impact factors.

PMID- 20670526
TI  - Technical Aspects of Intra-arterial Electroencephalogram Recording.
AB  - SUMMARY: The purpose of this prospective study is to show a technique for
      recording electroencephalographic activity via an endovascular approach in
      presurgical evaluation of epileptic patients. Technical aspects and insertion
      strategy are outlined. Advantages of intra-arterial electroencephalography have
      been demonstrated. It is a semi-invasive procedure that provides information in
      temporal lobe and extratemporal epilepsy. It allows a dynamic
      electroencephalographic recording and patient tolerance is excellent. Risks are
      practically absent. Disadvantages are: in comparison to ovale electrodes, chronic
      and multicontact recording is not possible and the recording is only
      intercritical.

PMID- 20670527
TI  - Stenting for stenoses of the proximal vertebral artery.
AB  - SUMMARY: We report our initial experience of stenting for symptomatic stenoses of
      the proximal vertebral artery. A total of 25 lesions affecting the proximal
      vertebral artery were treated by PTA with stent in 23 patients. The lesions
      involved the vertebral artery ostium in 20 lesions and the nonostial VI portion
      in five lesions. The mean stenosis rate of those lesions was 81% pre-stenting and
      was reduced to 4% post-stenting. There were two transient neurological
      complications: hemiparesis in one patient and visual acuity disturbance in
      another. Angiographic followup studies more than three months after treatment
      demonstrated restenosis in three patients. One of these patients was symptomatic.
      These restenoses were successfully treated by PTA. Our initial results
      demonstrated that stenting is a feasible and safe method of treating stenosis of
      the proximal vertebral artery.

PMID- 20670528
TI  - Is the foramen caecum the uppermost part of the spinal medulla?

PMID- 20670529
TI  - Carotid-Cavernous Fistula Associated with Ehlers-Danlos Syndrome Type IV. A Case
      Report and Review of Literature.
AB  - SUMMARY: A case of traumatic, direct, carotid cavernous fistula (CCF) associated
      with Ehlers - Danlos syndrome (EDS) Type IV is reported along with a review of
      the literature. Excluding the present case, three similar cases associated with
      EDSTypeJV have already been reported by Gerard M. Debrun et Al(l). Despite the
      risks associated with endovascular manipulation, the fistula was successfully
      closed by intravascular embolisation but the patient expired a few days later
      because of underlying disease-associated vascular and visceral complications.

PMID- 20670530
TI  - Embolisation of a persistent primitive trigeminal artery for a large cavernous
      aneurysm. A case report.
AB  - SUMMARY: We report a case of large cavernous aneurysm associated with persistent
      primitive trigeminal artery (PPTA). Thrombosis of the aneurysm was obtained only
      by occlusion of the PPTA. Aneurysms associated with PPTA have not previously been
      treated only by the occlusion of PPTA with GDC, and this report presents the
      first such intervention. A radiological follow-up study with MRI and angiography
      demonstrated marked shrinkage of the thrombosed aneurysm 17 months later,
      although clinical symptoms were not improved. From our experience, we suggest
      that the occlusion of the P PTA can be the first step in the therapeutic protocol
      for aneurysms associated with PPTA.

PMID- 20670531
TI  - Spontaneous thrombosis of an intracranial giant aneurysm.
AB  - SUMMARY: Spontaneous thrombosis in giant aneurysms is known, whereas complete
      occlusion of such aneurysms in a short period of time is rarely reported. We
      present the case of a 50-year-old man with a giant anuersym arising from the
      anterior communicating artery (ACA) producing significant mass effect with
      clinical consequences. The digital subtraction arteriogram (DSA) showed a patent
      lumen of about 20 mm and a very small neck leading to extremely slow blood flow
      inside the sac and stagnation of contrast. During catheterization for
      endovascular occlusion four weeks later, the arteriogram revealed complete
      disappearance of the aneurysm, while the patient remained clinically stable. The
      patient was operated upon and the thrombosed sac was removed with no
      complications. He was discharged one week later and recovered completely from his
      symptoms within three months.

PMID- 20670532
TI  - The vessel wall remodelling technique using a coronary angioplasty balloon and a
      single guide catheter.
AB  - SUMMARY: The vessel wall remodelling technique was created by Moret to enable
      endovascular therapy of relatively wide-necked cerebral aneurysms. As originally
      described, two guide catheters are placed in the relevant vertebral or carotid
      artery, and a Solstice balloon (Micro Interventional Systems, Ca, USA) inflated
      across the neck of the aneurysm while coils are placed inside. I describe a
      modification of this technique, using a single guide catheter, and a "monorail"
      coronary artery angioplasty catheter.

PMID- 20670533
TI  - An improvement of cerebral hemodynamics following percutaneous transluminal
      angioplasty in patients with atherosclerotic arterial stenosis.
AB  - The purpose of this study was to evaluate changes in cerebral hemodynamics
      following percutaneous transluminal angioplasty (PTA) in patients with
      atherosclerotic cerebral arterial stenosis. PTA was performed on the patients
      under the condition that the arterial stenosis ratio was 70% or more and regional
      cerebrovascular reserve (rCVR) had decreased to 10% or less. Resting regional
      cerebral blood flow (rCBF) and rCVR responding to acetazolamide loading were
      measured by (133)Xe single photon emission tomography (SPECT) just prior to and 1
      month after PTA. The average stenosis ratio was significantly improved from 77%
      to 36% one month after PTA. There were 185 preoperative normal rCBF and normal
      rCVR regions, 176 region (95%) of which retained their normal rCBF and normal
      rCVR postoperatively. In 9 regions (5%) only rCVR worsened. Preoperatively, there
      were 59 normal rCBF and decreased rCVR regions. Forty-five (76%) regions later
      showed normalized rCVR. Six regions (10%) remained decreased rCVR regions; no
      region did not worsen during the course of this study. Twenty-nine regions of
      both preoperative resting rCBF and rCVR decreased regions. Postoperatively, 18
      regions (62%) normalized in regards to both rCVR and resting rCBF; in 4 regions
      (14%), only the resting rCBF was normalized. In the 24 decreased rCBF and normal
      rCVR regions, there were no hemodynamic alterations after PTA. Regions with
      decreasing rCVR are at high risk of future brain infarction. This study indicates
      that the risk of cerebral infarction was avoided by PTA in the low rCVR regions.

PMID- 20670534
TI  - Percutaneous transluminal angioplasty for atherosclerotic stenosis of the
      intracranial cerebral arteries. initial results and long-term follow-up.
AB  - Percutaneous transluminal angioplasty (PTA) was carried out 52 times for 49
      lesions in 47 cases of atheroscrelotic stenosis of the intracranial or skull base
      cerebral arteries. The stenotic lesions involved the middle cerebral artery in 21
      cases, the basilar artery in eight cases, the internal carotid artery (petrous
      supraclinoid portion) in 15 cases, and the intracranial vertebral artery in five
      cases. Nearly all cases were symptomatic, such as TIA or stroke, and the degree
      of stenosis ranged from 70 to 99 percent, with a mean of 80 percent. PTA was
      performed using a STEALTH balloon angioplasty catheter. In these trials, PTA was
      successfully performed (as indicated by a residual stenosis under 50%) 41 times.
      The initial success rate was 79% and stenosis was reduced from 80% to 25%.
      Clinical follow-up was performed from 7 to 84 months with a mean of 44 months.
      During this period, death due to myocardial infarction or pneumonia occurred in
      five cases, stroke related to previous PTA occurred ih one case (due to re
      stenosis) and stroke unrelated tl? previous PTA occurred in two cases.
      Angiographic follow-up was performed in 31 cases after 41 successful PTA
      procedures. Re-stenosis was seen in 20% of the cases, symptomrltic complications
      occurred in 6%, and asymptomatic complications occurred in 6% of the cases. One
      case suffered severe subarachnoid hemorrhage just after the PTA due to
      preexisting aneurysm rupture and he died a week after the PTA. So mortality in
      this series was 2%. From the results described here, we may conclude that PTA of
      the intracranial or skull base cerebral artery is technically feasible, and it
      can be performed with relatively low risk. From our results, it may be a useful
      method and effective for long-term survival of patients. But results from a
      larger number of patients and more long-term follow-up data are still necessary
      in order to evaluate the safety and usefulness of this method.

PMID- 20670535
TI  - Initial experiences of carotid stenting with palmaz stent.
AB  - Results of cervical carotid stenting are reported. Twenty-nine lesions in 25
      cases were treated by percutaneous transluminal balloon angioplasty combined with
      stent placement. All the lesions were successfully dilated. There was one embolic
      complication during the operation that caused deterioration of preoperative
      symptoms. Stent deformation causing more than 30% luminal narrowing occurred in
      one case. Instent restenosis with more than 50% luminal narrowing was seen in
      bilateral lesions in one case. These were satisfactory results as an initial
      experience, but further improvement in this technique is considered essential
      especially to avoid embolic complications.

PMID- 20670536
TI  - Stenting therapy for extra-cranial carotid stenosis.
AB  - We report our initial results of stent placement for extra-cranial carotid
      stenosis. Fifteen patients aged 54 to 83 years (10 men) with > 60% extra-cranial
      carotid stenosis were treated with percutaneous stent implantation. Four patients
      were asymptomatic. The rate of stenosis ranged from 60% to 93% (mean: 74%).
      Balloon-expandable stents (Palmaz stent: 11, Cordis stent: 1, GFX stent: 2) were
      placed for fourteen patients and for one patient a self-expandable stent was used
      (Memotherm biliary stent). The proximal protective balloon technique was used in
      the most possible cases during predilatation or stent placement. Angiography or
      ultrasonography was performed as the evaluation of restenosis after stent
      placement. The definition of restenosis was > 50% stenosis. The mean period of
      follow-up was 8.5 months (from 1 to 20 months). In all patients, carotid stents
      were successfully placed. The mean rate of stenosis immediately after the
      procedure decreased to 0%. The protective balloon technique could be used in ten
      patients during pre-dilatation, in six during stent placement. One patient
      suffered a transient ischemic attack immediately after predilatation. The
      symptoms disappeared completely 15 minutes after onset. There was no patient with
      relapse or deterioration of neurological deficits after the procedure. There was
      no restenosis and stent deformation in the follow-up period. In our small series,
      stent placement for extra-cranial carotid stenosis was performed with a low rate
      of morbidity and mortality. However, it is necessary to develop more flexible,
      more controllable stents with increased mesh densities for exclusive
      neurointervention. In addition, the development of a more reliable protective
      balloon technique to decrease procedurerelated complications is needed.

PMID- 20670537
TI  - Endovascular treatment for internal carotid stenoses. long-term follow-up results
      and overall complications.
AB  - Seventy four cases of internal carotid stenoses greater than 60% were treated by
      PTA and/or stenting 86 times. Sixty one cases of cervical ICA stenosis were
      treated 71 times. 11 cases of high cervical - intracranial ICA stenosis were
      treated 13 times. Two cases of ICA dissection were treated by stent deployment.
      Stenotic ratio reduced from 79% to 29% in cervical ICA stenosis and 71 % to 32%
      in high cervical to intracranial ICA stenosis in average. Morbidity related to
      PTA and/or stenting was 2/74 (2.7%) and mortality was 0%. One was an ischemic
      complication and the other was a hemorrhagic complication due to hyperper fusion.
      Restenosis (stenosis greater than 70%) rate was 32%. Asymptomatic cerebral
      embolism were found in three cases (4.2%) on angiogram immediately after PTA
      and/or stenting. The complication rate related to PTA and/stenting was low but
      asymptomatic emboli were found in three cases. Considering these results, the
      indication for PTA and/stenting should be restricted to patients with high risk
      group, such as cases with high medical risks or difficult CEA cases, if
      appropriate protective systems for cerebral emboli were not available.

PMID- 20670538
TI  - Distal flow protection during carotid stenting. a prospective study to quantify
      the embolic debris retrieved in the internal carotid artery territory.
AB  - This study was conducted to evaluate presence of embolic debris during ICA stent
      procedures. Nine patients with severe carotid atheromatous stenosis were treated
      by stent implantation under distal flow protection using a non-detachable
      balloon. After stent implantation, the lumen of the ICA was cleaned by aspiration
      of 50 cc of blood before further flush cleaning and deflation of the protection
      balloon. The blood samples obtained from each patient were analyzed using a
      microscope to check quantity and aspect of embolic debris. Significant numbers of
      embolic debris were recovered from blood samples in all nine stenting cases, but
      very few were found in four out of the five control cases. This observation
      demonstrates the high risk of producing embolic debris during carotid stenting.
      Distal balloon occlusion and cleaning procedures are techniques to provide
      protection from thromboembolic complications to the brain.

PMID- 20670539
TI  - Stenting treatment for intra- and extra-cranial atherosclerotic diseases.
AB  - The purpose of this study was to investigate the effect, safety and short-term
      outcome of stenting treatment for extra- and intra-cranial atherosclerotic
      diseases. Forty-one patients underwent stenting treatment using coronary and
      biliary stents. Eleven patients had tubular or diffuse high-grade stenoses not
      amenable to standard balloon angioplasty involving intra-cranial arteries, while
      in thirty, extra-cranial arteries were involved. Stents were successfully
      implanted in 36 out of 41 lesions (88%) with 2% (1/41) of overall procedural
      morbidity rate. Procedural and clinical success rate of intra-cranial stent
      placement was 64% (7/11) and no complications occurred during or after intra
      cranial stent placement: the morbidity rate was 0%. Hyperperfusion injury
      occurred in two patients after successful implantation of stents in subtotal
      occlusion of the internal carotid artery, and consequently the overall clinical
      success rate was 80% (33/41). Restenosis occurred in four (12%) out of 33
      patients who underwent six month follow-up arteriography. No ischemic attacks or
      stent-deformation occurred during follow-up after stenting treatment. For lesions
      not amenable to standard balloon angioplasty, endovascular stent placement seems
      to be a safe and effective treatment of modality.

PMID- 20670540
TI  - Initial and long-term results and peri-procedural complication in 35 extracranial
      stentings.
AB  - We undertook stent-supported angioplasty for 35 lesions of extracranial stenosis
      in 31 patients from May 1996 to October 1998. We succeeded in the stenting at the
      predetermined sites of all lesions and excellent initial results were obtained.
      The mean % stenosis decreased from 81% to 7.1% after stenting. Four patients had
      neurological complications related to the procedure. There were two transient
      ischemic attacks (one in carotid and one in vertebral stenting), and permanent
      deficits occurred in two patients treated for carotid stenosis. In carotid
      stenting, we observed long-term patency for over six months in all 17 patients
      (18 lesions). Mean angiographic, asymptomatic restenosis was 20% and 21% at three
      and six months, respectively (range, 4 to 38%). No further stenosis was observed
      thereafter. Deformity of the stents were not noted in any patient. In vertebral
      stenting, four out of nine cases revealed significant restenosis between three
      and six months later, while these were dilated by repeated PTA. On strict
      definition of indication or application of a cerebral protection, stent-supported
      angioplasty is an effective method for the treatment of extracranial stenotic
      lesions.

PMID- 20670541
TI  - Carotid angioplasty.
AB  - Although no consensus yet exists on the ideal patient characteristics, materials,
      and indications for carotid angioplasty, it is clear that this procedure which is
      increasing in popularity will continue to do so. Until such time as the procedure
      is routinely approved (there are still barriers to insurance coverage for these
      procedures in the United States), we are highly selective in our application of
      carotid angioplasty. So far our experience is limited to approximately 40
      patients with no major complications and no strokes. However, patient
      characteristics, operator experience, and patient selection play large roles in
      the outcomes of these procedures. The current status of carotid angioplasty and
      stenting will be discussed as well as the potential complications and their
      treatment.

PMID- 20670542
TI  - Endovascular treatment using detachable coils for non-ruptured intracranial
      aneurysm.
AB  - Detachable coil embolization was performed on 34 non-ruptured cerebral aneurysms
      in 33 patients. Patients consisted of 28 females and five males, with an age
      range of 26 to 77 years. Angiographic examination after coil embolization
      revealed complete or near-complete occlusion in 24 aneurysms (70.5%) and partial
      occlusion in three (8.8%). Detachable coil embolization was attempted
      unsuccessfully in seven aneurysms (20.5%). Transient ischemic attack occurred in
      one case with coil migration. The combined mortality/morbidity rate was 0%.

PMID- 20670543
TI  - Endovascular treatment of vertebrobasilar aneurysms. Occlusion of the vertebral
      arteries and flow inversion.
AB  - In posterior circulation aneurysms, GDC endosaccular occlusion is the treatment
      of choice, when indicated. This report assessed anatomical, morphological and
      clinical criteria in the choice of vertebral or basilar artery occlusion in
      posterior circulation aneurysms, when GDC endosaccular treatment, with or without
      the "remodelling technique", is not indicated, as in giant or wide-neck
      aneurysms. Over five years we observed eleven patients harboring posterior
      circulation aneurysms with no indication for treatment with GDC, or only
      vertebral occlusion. In our experience, the endovascular occlusion of a single or
      both vertebral arteries or basilar artery, following a detailed anatomical and
      clinical assessment, has proved a good, reliable treatment in large or giant
      vertebrobasilar aneurysms or those without a neck.

PMID- 20670544
TI  - Endovascular treatment of incidental cerebral aneurysms. report on 115 cases
      treated with guglielmi detachable coils.
AB  - One hundred and fifteen patients with 120 intracranial incidental aneurysms were
      embolized using the GDC endovascular technique at UCLA Medical Center.
      Angiographic results showed complete or near complete aneurysm occlusion in 109
      aneurysms (91%) and an incomplete occlusion in five aneurysms (4%). An
      unsuccessful GDC embolization was attempted in six aneurysms (5%). One hundred
      and nine patients (94.8%) remained neurologically intact or unchanged from
      initial clinical status. Five patients (4.3%) deteriorated due to immediate
      procedural complications. All these complications occurred in the first 50
      patients. No clinical complications were observed in the last 65 patients .. In
      Groups 1 and 3, the average length of hospitalization was 3.3 days. The technical
      evolution of the GDC technology has proved to be safe for the treatment of
      incidental aneurysms (0% morbidity in the last 65 patients). The topography of
      the aneurysm/s and the clinical condition of the patient did not influence final
      anatomical or clinical outcomes. GDC technology also brings a positive economical
      impact by decreasing hospitalization time and eliminating postembolization ICU
      care.

PMID- 20670545
TI  - Endovascular treatment of unruptured vertebro-basilar aneurysms.
AB  - We reviewed 201 unruptured vertebro-basilar aneurysms encountered at our
      institute and 35 affiliated hospitals over the past 8 years. Of these, 106
      aneurysms in 103 patients were treated with surgical or endovascular approaches:
      43 aneurysms, surgically with clipping or wrapping; and 63 endovascularly with
      embolization. Outcome was excellent or good in 87 patients (84.5%). Among 24
      patients with 36 complications, 16 had unfavorable outcomes including five
      deaths. Twelve patients (27.9%) with surgical treatment and two (3.3%) with
      endovascular treatment had unfavorable results because of treatment-related
      complications. Two patients with surgical treatment had complications related to
      perioperative management. Vascular occlusive complications were likeliest to
      occur in surgically treated basilar artery aneurysms (41%). Among surgically
      treated aneurysms the vertebral artery site was relatively associated with
      cranial nerve injuries. Complications numbered 36, occurring in 24 patients and
      54% of complications affected outcome. Overall morbidity and mortality of
      surgical treatment were 18.6% and 7.0%, respectively, while those of endovascular
      treatment were 5.0% and 3.3%. In conclusion, complications of surgery tend to be
      serious and affect outcome, and endovascular treatment is safer than surgical for
      vertebro-basilar aneurysms. Embolizations are particularly advantageous for
      patients who are poor surgical risks.

PMID- 20670546
TI  - Follow-up study on intra-aneurysmal embolization for unruptured cerebral
      aneurysms.
AB  - We describe follow-up clinical and angiographical results in patients with
      unruptured cerebral aneurysms treated with IDC or GDC. In 28 patients who
      underwent intra-aneurysmal occlusion for unruptured aneurysms, there were no
      permanent neurological deficits in the periprocedural period, while three
      transient neurological deficits were observed. On the angiograms obtained
      immediately after the procedure, complete aneurysmal occlusion was achieved in
      three patients (10.7%), a small neck remnant was detected in two cases (7.1%), a
      body filling in 12 cases (42.9%) and both of them were detected in 11 patients
      (39.3%). On the follow up angiograms (median angiographical follow-up period 15.6
      months), 46.4% of incompletely obliterated aneurysms showed aneurysmal
      recanalization, and a incompletely embolized aneurysm ruptured 15 months after
      initial embolization. Detachable platinum coil embolization is a safe treatment
      for unruptured aneurysms with a lower incidence of peri-procedural morbidity,
      wheareas follow-up results are less satisfactory in cases involving incompletely
      obliterated lesions. With this limitation in mind, patients need to be very
      carefully chosen for GDC embolization and strict follow-up angiography is
      mandatory when a complete embolization is not achieved.

PMID- 20670547
TI  - Embolization of non-ruptured aneurysms.
AB  - Options for treatment of intracranial aneurysms have expanded with the advent of
      the Guglielmi Detachable Coil (GDC) eight years ago. We have reviewed 435 cases
      of intracranial aneurysms treated at UCSF by endovascular means using the GDC
      system. Of these, 55% represent anterior circulation aneurysms, and 45% are
      located in the posterior circulation. Additionally, 55% of the aneurysms
      presented with subarachnoid hemorrhage (SAH) and 45% were unruptured. Factors
      which hindered optimal coiling include the following: wide aneurysm neck in
      relation to the overall aneurysm size, mural thrombus, giant aneurysm, arteries
      originating from the aneurysm sac, and middle cerebral location. After initial
      experience was gained, we tended to avoid these aneurysms especially in the non
      ruptured group. This may be especially important in light of new epidemiological
      data suggesting that the natural history of unruptured aneurysms is significantly
      lower than previously thought. New technical developments which may reduce the
      risk of treating unruptured aneurysms include the two-dimensional coil, the three
      dimensional coil, the balloon-assist technique for wide-necked aneurysms, and
      combined stent-coil procedures.

PMID- 20670548
TI  - Preoperative tumor embolization.
AB  - We performed an embolization of tumors which we considered to need preoperative
      embolization, such as deep-seated tumors, or hypervascular tumors. We experienced
      12 such cases in the two-year period from September 1996. Eight cases were
      meningiomas, one case was a hemangiopericytoma, one case was an angiofibroma and
      two cases were glomus tumors. As embolic material, we usually use estrogen
      alcohol and polyvinyl acetate which soften the tumor. When a provacative test is
      either impossible or positive, the distal induction of a microcatheter is
      impossible or a dangerous anastomosis is present, we select polyvinyl alchol
      particles (120 approximately 250mum) and liquid coils. We performed an
      embolization of a very hypervascular tumor, juvenile angiofibroma, by a direct
      tumor puncture, using a mixure of N-butylcyanoacrylate, lipiodol and tantalum
      powder. Angiography in all cases showed a reduction of the tumor stain. The
      embolic method should be selected based on a combination of such factors as the
      purpose of embolization, the identification of the feeding artery and the
      histological findings.

PMID- 20670549
TI  - How to embolize wide-necked aneurysms? Two embolization techniques for wide
      necked aneurysms.
AB  - Novel endovascular approaches are needed for safer and more definitive treatment
      of wide-necked aneurysms, to overcome the limitations of the Guglielmi detachable
      coil (GDC) system and further, the application of this technique. The double GDC
      technique (DGT), for embolization of wide-necked aneurysms, and the combination
      of stent placement and coil deposition(CTSC) for management of fusiform aneurysms
      have been developed and their usefulness is reviewed. The DGT involves
      scaffolding of a GDC coil to form a stabilizing frame inside the aneurysmal neck
      and then positioning of a second coil to reinforce the first coil. After
      confirming the absence of coil herniation in the parent artery, both coils are
      released together. A patient with a wide-necked large aneurysm of the left
      internal carotid artery was treated using this technique, and followed up
      angiographically and clinically for a period of three months. The follow-up
      angiograms revealed complete embolization of the aneurysm. The patient had no
      neurological changes or adverse events during the procedure. The CTSC involves
      reconstructing the artery with a stent and packing the aneurysm lumen with GDCs
      through the stent interstices. A patient with a dissecting fusiform aneurysm of
      the vertebral artery associated with hypoplasia of the contralateral vertebral
      artery was treated using this technique to prevent rebleeding. His clinical
      course was uneventful over a six-month follow-up period. Angiography performed
      two months after the procedure confirmed excellent flow through the right
      vertebral artery and absence offilling of the daughter aneurysm.

PMID- 20670550
TI  - The rebuilding of normal venous circulation for transverse-sigmoid dural
      arteriovenous fistulas by percutaneous transluminal angioplasty. A case report.
AB  - The etiology of dural arteriovenous fistulas (DAVFs) remains controversial as is
      the issue of whether occlusion or stenosis of the transverse sinus and sigmoid
      sinus is a cause or a result of DAVFs. We report a case of DAVFs with transverse
      sigmoid sinus occlusion and cortical venous reflux. In this case, the
      reconstruction of normal venous circulation by percutaneous transluminal
      angioplasty (PTA) for the occluded sinus was performed and cortical venous reflux
      diminished. PTA may be a useful treatment for DAVFs with occluded or stenotic
      sinus.

PMID- 20670551
TI  - Treatment of intracranial (dural) arteriovenous fistulas in unusual locations.
AB  - We evaluated retrospectively the treatment modalities and clinical outcome of 14
      patients with intracranial dural arteriovenous fistula (AVF) involving cortical
      veins and dural sinuses except the cavernous and lateral sinuses. The location of
      arteriovenous shunt was the confluence of the sinuses and superior sagittal sinus
      (in 2 patients), superior petrosal sinus (1), marginal sinus (1), parasigmoid
      sinus (1), cortical vein at the anterior fossa (2), cortical vein of the parietal
      lobe (2), petrosal vein (2), and the cortical vein around the craniocervical
      junction (3). Of 12 patients who underwent endovascular andlor surgical
      treatment, five patients were treated only with microsurgery, six only with
      endovascular therapy, and one with combined surgical and endovascular procedure.
      Angioanatomical result was complete occlusion of the lesion in all the cases
      treated with surgery, and 80 to 100% occlusion in cases with endovascular
      treatment. Clinical outcome was GR in nine patients, MD in two, SD in one, VS in
      one, and D in one. The natural history of the lesion at each location and
      angioanatomical feature including the hemodynamic condition in each case should
      be precisely evaluated to select endovascular, surgical, or a combined procedure
      for the management of these unusual types of intracranial dural AVF.

PMID- 20670552
TI  - Embolization of scalp AVF.
AB  - We report scalp arteriovenous fistulas (AVFs) in which we performed embolization
      and examine the treatment method. The subjects were four cases of scalp AVF
      treated by embolization. All cases were male and three had a past history of
      scalp injury. As the feeding artery, we found a single artery in one case and
      multiple arteries in three cases. In three cases we employed a transarterial
      approach by cutting down the scalp and embolized the fistula with NBCA (N-butyl
      cyanoacrylate). We conducted the embolization procedure as follows in order to
      securely occlude the fistula; 1) we obtained the precise location of fistula by
      the superselective angiography; 2) we induced the tip of microcatheter to
      immediately in front of fistula; 3) when high flow shunt was manifested, we
      controlled the flow by retaining the balloon catheter in the external carotid
      artery; 4) and injected NBCA by compressing around the fistula from above the
      scalp with a cylindrical instrument to prevent the migration of embolic material
      to the venous side. As a result, all cases were completely cured and there was no
      major complication except for transient postoperative pain. If the transfemoral
      approach to fistula is impossible, it is considered effective to cut down near
      the fistula and embolize the scalp AVF by direct puncture to the feeding artery
      with NBCA as embolic material.

PMID- 20670553
TI  - Interventional neuroangiography in neonates.
AB  - Two neonates with either vein of Calen aneurysmal malformation or dural sinus
      malformation (congenital dural arteriovenous fistula at the torcular herophili)
      are reported. In neonatal interventional neuroangiography, special attention
      should be paid to body temperature, contrast material, infusion fluid, heparin,
      and angio-equipment. In the neonatal period, the umbilical approach provides
      unique access routes to both arterial and venous sides of the cerebral
      circulation. Among them, transumbilical venous, transcardiac approach through the
      foramen ovale allows transarterial intervention from the venous side.

PMID- 20670554
TI  - Angioplasty for the infusion of fasudil hydrochloride to treat cerebral
      symptomatic vasospasm.
AB  - The present report describes the successful treatment of cerebral symptomatic
      vasospasm (SVS) after subarachnoid hemorrhage (SAH) with super-selective intra
      arterial infusion of fasudil hydrochloride (ERIL((R))). We treated seventeen
      vascular territories in 12 patients with selective intra-arterial infusion of
      fasudil hydrochloride (FSD). FSD was infused through a catheter (a microcatheter
      in nine patients) at a rate of 1.0 to 1.5 mg/minute (total dose=30 to 60mg/1
      vessel) for each vascular territory. Nineteen vascular territories (100%) were
      angiographically dilated and seven patients (58%) showed early improvement in
      neurological function after the procedure.

PMID- 20670555
TI  - Indication of thrombolysis for middle cerebral artery occlusion using MR
      diffusion - weighted image.
AB  - We have evaluated the usefulness of diffusionweighted MRI (DWI) for determining
      an indication of emergent thrombolytic revascularization therapy in patients with
      acute occlusive cerebrovascular disease. Out of twenty-nine patients with acute
      occlusion of the middle cerebral artery within six hours after the onset, nine
      patients performed thrombolytic therapy. In results, seven patients of them
      obtained revascularization and good outcome. DWI findings on admission were
      correlated to the cerebral blood flow measured by SPECT and classified into four
      types; Type 1: no high intensity, Type 2: high intensity only in the perforator's
      territory, Type 3: limited high intensity in the cortical branches' territory,
      Type 4: extended high intensity. As presented cases, the high intensity area seen
      on DWI became obvious infarction regardless of implementation of
      revascularization therapy. However, thrombolytic therapy could rescue the area of
      low CBF on SPECT and could improve clinical symptoms. We considered that the area
      of low CBF without high intensity on DWI was "ischemic penumbra" and
      classification of DWI findings could be a valuable indicator in determining an
      indication of thrombolytic therapy.

PMID- 20670556
TI  - Angiographic classification of cerebral embolism. Relation with the response to
      local intra-arterial thrombolysis.
AB  - Since 1994, we have treated 62 cases with hyperacute cerebral embolism with local
      intraarterial thrombolysis (LIT), but not all cases showed recanalization. We
      tried to classify these cases by angiographic results. Angiographically they
      could be classified into four types; tapering type, fading type, stump type, and
      edge type. The tapering and fading type had a significantly higher tendency to
      recanalize than the stump and edge type. We think these classifications indicate
      the dissolubility of the cerebral emboli; the former two types dissoluble, the
      latter two types indissoluble. The tapering and fading type are the good
      indicators for LIT, but the stump and edge type may not be.

PMID- 20670557
TI  - Effectiveness and pitfall of embolization of cerebral arteriovenous
      malformations.
AB  - We studied the course ofperisurgical complications of 66 AVMs and discussed the
      approapriate precautions. Of 66 patients with AVMs, 14 underwent postembolization
      surgical removal, and 43 underwent radiosurgery. Four patients were cured with
      total occlusion of their AVM by embolization alone. 48 patients achieved a more
      than 70% occlusion of the nidus. We observed 12 complications including 3
      permanent and 9 temporary. Four complications occurred immediately after the
      embolization due to overembolization or thromboembolism, and 7 were observed
      several hours later which might have been caused by retrograde thrombosis or a
      chemical reaction to the glue. While presurgical embolization deepseated feeders
      must be embolized along with fistulous or high-flow feeders, 4 cases of 2nd
      embolization following radiosurgery showed that meningeal feeders developed or
      recanalized in cases embolized with absorbable particles. Thus,
      preradiosurgically, fistulous and meningeal feeders should be treated, and the
      nidus must be packed with embolic materials with no risk of recanalization.
      Successful nidus packing performed in 10 AVMs yielded a further nidus reduction
      before radiosurgery. The intranidal aneurysms which pose a high risk of
      rebleeding were also embolized. In order to avoid complications in the
      embolization of AVM, the angioarchitecture, hemodynamics and the relationship to
      brain function should be well recognized by preoperative functional imaging and
      superselective angiograms, and adequate embolic materials should be properly
      injected. As an embolization strategy, the priority of the target feeders should
      depend on the treatment to follow, and aggressive embolization of risky feeders
      or causing abrupt hemodynamic change should be avoided.

PMID- 20670558
TI  - Angioarchitecture predicting hemorrhage in cerebral arteriovenous malformations.
AB  - To find out lesions responsible for hemorrhage in arteriovenous malformations
      (AVMs), a retrospective study of angioarchitecture around the nidus was conducted
      in 27 patients who underwent conservative treatment. Comparison of angiograms
      revealed disappearance of an intranidal aneurysmal dilatation after the
      hemorrhagic events in two cases. The hematomas were adjacent to the dilatation,
      and no subarachnoid hemorrhage was evident. Obstruction of venous drainage,
      noticed in a case of spontaneous regression of AVM, was not demonstrated in the
      cases of hemorrhage. The intranidal aneurysmal dilatation is likely to have
      caused the hemorrhage in our cases. Careful endovascular embolization using
      proper materials should be indicated for an intranidal aneurysmal dilatation to
      prevent subsequent hemorrhage.

PMID- 20670559
TI  - Efficacy of diluted NBCA mixture for embolization of arteriovenous malformations.
AB  - The purpose of this study is to evaluate the efficacy and problems of the
      embolization for cerebral arteriovenous malformations (AVMs) with diluted
      cyanoacrylate adhesives. Twelve consecutive AVM cases were treated with N-butyl-2
      cyanoacrylate (NBCA) glues between January 1997 and July 1998. The mean age of
      the patients was 37 years old. Intracerebral hemorrhage was the presenting
      symptom in seven cases, seizure in three, headache in one and mental
      deterioration in one. According to the classification of Spetzler and Martin,
      seven were Grade II, five were Grade III. We used a mixture of NBCA (normally 25%
      Histoacryl, 75% Ethidol) for embolization. Microcatheter was navigated into the
      nidus and the tip of the catheter was set in a wedged position. Then the glue was
      injected using complete column technique. Nineteen sessions of embolization were
      performed in 12 patients. The mean volume of each nidus was reduced from 22.5 ml
      to 3.4 ml (85%) after embolization. Four cases were cured by embolization alone.
      Surgical resection was performed after embolization without any residual nidus in
      three cases. Five were treated with stereotactic radiosurgery following
      embolization. One was completely cured in 18 months after and the other four have
      been decreasing their sizes of nidus. One case was suffered from delayed
      intracerebral hemorrhage three days after embolization, and resulted in mild
      hemiparesis and memory disturbance. The others had no complications and were
      clinically improved or unchanged after embolization. It is possible to embolize
      the nidus of AVMs more accurately and safely with diluted mixture of NBCA,
      compared with the method using relatively higher concentration of NBCA glues.
      This technique is useful and effective method for the treatment of AVMs.

PMID- 20670560
TI  - The selection and result of AVM treatment.
AB  - The treatment selection for cerebral arteriovenous malformation (AVM) still is in
      controversy. In order to find out the best way to treat AVM, we summarized the
      treatment result of AVM patients in our hospital. Sixty-three AVM patients who
      had been treated at Nagoya University Hospital since 1988 to 1997 were studied.
      The patient characteristics were nearly the same as other reported series. The
      treatment modalities include surgery, embolization and radiosurgery. Rate of
      nidus disappearance was assessed in each treatment. Highest rate was observed in
      surgery or surgery with embolization. But new neurological deficits were seen in
      37% of the patients of same group. Nidus occlusion rate was not high in
      radiosurgery with embolization, but low in complication rate. The result showed
      the importance of embolization procedure in the treatment selection of AVM. The
      value of functional MRI as pre-therapeutic study is high in those patients whose
      AVM adjacent to eloquent area.

PMID- 20670561
TI  - The role of intravascular embolization prior to radiosurgery of cerebral
      arteriovenous malformations. from the standpoint of hemorrhage and early
      obliteration after gamma knife radiosurgery.
AB  - The role of intravascular embolization prior to radiosurgery of cerebral
      arteriovenous malformations was evaluated based on the basis of the results of
      gamma knife radiosurgery in relation to hemorrhage and early obliteration after
      treatment. Nine of 213 patients experienced hemorrhage 4 to 42 months after
      radiosurgery. All AVMs in these patients had dilated feeding arteries, and the
      flow of the AVM was rapid and/or high. An intranidal aneurysm was seen in one
      patient. Drainage of all AVMs consisted of a single and/or deep draining veins,
      and venous obstruction was found in six. Sixty-three of 87 patients followed for
      more than four years after radiosurgery were examined angiographically, and total
      obliteration of AVM was observed in 52 of them (82.5%). Early obliteration was
      found in 19 of the 34 patients examined within 12 months. The obliteration rate
      was significantly higher in slow- and low-flow AVMs (73.9%) than in rapid- and/or
      high-flow AVMs (18.2%). It is concluded that the role of intravascular
      embolization prior to radiosurgery is not only decreasing the size of the AVM but
      decreasing the risk of hemorrhage and shortening the latency period by decreasing
      their flow rate and flow volume.

PMID- 20670562
TI  - Hemodynamic perturbations in cerebral arteriovenous malformations and management
      implications.
AB  - Cerebral AVMs have high flow, low resistance shunts that induce regional
      hemodynamic disturbances and possibly neural derangements. A better understanding
      of these mechanisms may help treatment planning and the management of
      complications after endovascular or surgical treatment. Although the precise
      mechanisms of hemodynamic perturbation are still relatively unclear, the presence
      of chronic cerebral hypoperfusion is central and widely believed to be associated
      with both neurological deficits at presentation ('steal') and 'hyperemic'
      complications following shunt obliteration. The 'normal perfusion pressure
      breakthrough' (NPPB) theory states that chronic hypoperfusion around AVMs induces
      the loss of autoregulatory capability; following AVM shunt obliteration,
      perfusion pressure elevation induces an increase in flow, due to 'vasomotor
      paralysis', which can cause hemorrhage. The 'dissociative vasoparalysis' theory
      suggests that vasodilation is preserved but not vasoconstriction. However,
      pharmacologic exploration of cerebral autoregulation with induced
      vasoconstriction (phenylephrine) and vasodilatation (acetazolamide) helps
      identify 3 patterns of autoregulatory behavior. The vast majority of AVM patients
      appear to retain autoregulatory capability, despite low arterial feeding
      pressures, consistent with a "shift to the left" of the autoregulation curve.
      Pronounced hypotension may "exhaust" cerebrovascular reserve in some patients,
      predisposing to hemorrhagic complications in the post-operative period. Lastly,
      "vasoparalysis" may coexist with a combination of vascular insult and marked
      hypotension. Clinical presentation, AVM angioarchitecture and peri-operative
      physiologic data (especially feeding artery and venous outflow pressures) may
      assist patient management. Patients can be identified in whom staged treatment is
      recommended initially. Following AVM obliteration, the patient's hemodynamic
      response, which may range from a minimal increase in A-V pressure gradient to
      significant CBF increase may be predicted, and blood pressure, fluid and lCP
      management adjusted accordingly, as the monitoring of post-operative cerebral
      hemodynamics remains difficult. Extreme attention to endovascular and operative
      technique must be exercised, as technical problems can be devastating. Although
      incompletely understood, hemodynamic derangements associated with cerebralAVMs
      increasingly appear to be associated with intact cerebral autoregulation in most
      patients. As cerebral hemodynamics monitoring remains challenging, clinical,
      angiographic and physiologic data from interventional/operative monitoring must
      be used to guide patient management.

PMID- 20670563
TI  - Intra-aneurysmal GDC embolization for ruptured aneurysm in the acute stage.
AB  - This study focused on our experiences in intraaneurysmal embolization for
      ruptured aneurysm in the acute stage. Clinical materials of this study consist of
      37 patients who were treated with intra-aneurysmal GDC embolization within 72
      hours after the onset of subarachnoid hemorrhage from December 1995 to July 1998.
      Patients with cerebral aneurysms are always examined as possible candidates for
      neurosurgical clipping. If the patient had any difficulties and/or problems on
      neurosurgical clipping (high age 22, poor grade 15, surgically difficult location
      9, systemic disease 3), the patient was treated by intra-aneurysmal GDC
      embolization. GDCs were inserted as tight as possible. Then, spinal drainage was
      set in patients with thick subarachnoid hemorrhage. Tissue plasminogen activator
      was administered via the drainage in patients with thicker subarachnoid
      hemorrhage. One patient experienced rerupture during peritherapeutic period.
      Symptomatic vasospasm was observed in three patients (8.1%). Good outcome was
      obtained in 26 out of 30 surviving patients. Symptomatic complication caused by
      distal embolism occurred in two patients. In conclusion, intra-aneurysmal GDC
      embolization is thought to be sufficient regarding prevention of rerupture,
      incidence of vasospasm, and clinical outcome.

PMID- 20670564
TI  - Coil embolization for ruptured dissection on the vertebral artery distal to the
      origin of posterior inferior cerebellar artery.
AB  - Although many surgical or endovascular treatments for ruptured vertebral
      dissection have been reported, the best treatment remains controversial. Recently
      endovascular vertebral occlusion using coils has been reported, the appropriate
      occlusion site has not yet been fully discussed. Five cases of ruptured vertebral
      dissection located distally to the origin of posterior inferior cerebellar artery
      were occluded by platinum coil packing in the angiographical "pearl" portion or
      "fusiform dilatation" together with its proximal vertebral artery. All
      dissections were occluded completely together with occlusion of distal portion of
      vertebral artery to PICA's origin. No complications related to procedure were
      seen in this series. Occlusion of rupture point with preserving tiny perforators
      arising from vertebral artery would be an ideal method for this lesion. The
      present cases suggest that the short segment occlusion by coil packing in the
      angiographical "pearl" portion or "fusiform dilatation" together with its
      proximal vertebral artery would be near to the ideal.

PMID- 20670565
TI  - The embolization of ruptured aneurysms in acute stage with guglielmi detachable
      coils.
AB  - We have treated 43 ruptured aneurysms in 42 patients with Guglielmi Detachable
      Coils (GDC) in acute period. Thirty-one patients (74%) were independent on
      discharge. Among the patients of Hunt and Hess Grade I, II and III, 27 patients
      (84%) were independent. Acute rerupture occurred in two elderly patients with
      insufficient embolization and another patient experienced rerupture 45 days after
      the embolization. Symptomatic vasospasm was reported in 16% of patients and its
      permanent morbidity rate resulted in 3.1%. Although the long term results remain
      to be determined, embolization with GDC is a safe and promising treatment for
      acutely ruptured aneurysms.

PMID- 20670566
TI  - Endovascular treatment for ruptured cerebral aneurysms in acute stage.
AB  - Since the introduction of endovascular embolization with Guglielmi Detachable
      Coils (GDC) (1-3) in April 1997, we have performed 56 endovascular treatments for
      ruptured cerebral aneurysms in the acute stage based on our definition of
      candidates for this modality. Overall outcomes are as follows. 1) Rebleeding
      within one year was limited to one case (2.5%). 2) Vasospasm occurrences: four
      cases (7.1 %) infarction and three cases (5.4%) as transient ischemia. 3) H&K
      Grade IV: 60% of cases resulted in improved outcomes. 4) H&K Grade II: One case
      of rupture during an operation. 5) Three out offive older subjects (over 80 years
      old) resulted in GR or MD. In this study, we reviewed endovascular embolization
      in acute stage in terms of candidates and technical problems.

PMID- 20670567
TI  - GDC in ruptured versus unruptured aneurysms.
AB  - We have treated 581 aneurysms in 510 patients from August 1990 to November 1998.
      In 247 patients the presentation was acute rupture. In 141 patients the aneurysm
      treated was incidental. Complications in the acute group was 10.1% morbidity with
      2.8% procedure related mortality. The corresponding rates were 4.2% and 0% in the
      incidental group. In the incidental group all complications occurred up to 1995.
      In our last 91 patients there has been no morbidity or mortality. Anatomic
      outcomes were dependent upon aneurysm geometry in both groups. This low rate of
      complications when compared to the natural history for both ruptured and
      unruptured aneurysm favors treatment if the long-term follow-up confirms reduced
      longitudinal hemorrhage rates, and the aneurysm has a favorable geometry.

PMID- 20670568
TI  - Endovascular treatment for vertebral dissecting aneurysm presenting with
      subarachnoid hemorrhage.
AB  - We report results and problems of the endovascular treatment in 12 cases of
      intradural vertebral dissecting aneurysm presenting with subarachnoid hemorrhage.
      There were four complications related to interventional procedure and
      conventional angiography. In three patients (25%), VDAs ruptured immediately
      after injection of contrast media or hypertension during the interventional
      procedure, which caused respiratory arrest. In a case of bilateral VA dissection
      (8%), after proximal VA occlusion had been performed for unilateral VDA,
      contralateral dissection extended to the basilar artery resulting in brain stem
      infarct. We suggest that the incidence of rebleeding of VDA during angiography
      and embolization is higher than that of usual saccular aneurysms. Careful
      injection of contrast media and strict blood pressure control seems to be more
      important to prevent rebleeding in VDAs than intracranial saccular aneurysms.
      Since unilateral VA occlusion may extend contralateral dissection in a case of
      bilateral VA dissection, it is necessary to check contralateral VA dissection
      before VA occlusion.

PMID- 20670569
TI  - Comparison of clinical results between GDC treatment and direct surgery for
      ruptured cerebral aneurysms.
AB  - We present a comparison of clinical results between GDC treatment and direct
      surgery for ruptured cerebral aneurysms. From May 97 to April 98, 32 aneurysms
      were treated by direct surgery (DS) or GDC treatment. Treatments were selected
      depending on the clinical grade, degree of hematoma and anatomical aspect of the
      aneurysms. There were 13 GDC treated cases and 19 direct surgery cases. In GDC
      cases, there were acute stage embolization for ruptured basilar aneurysm,
      recurrence of case after clipping for BA-SCA aneurysm, advanced age cases, and
      systemic complication cases. Glasgow outcome scale (GOS) in GDC cases were 8 GR,
      2 MD and 3 SD. GOS in direct surgery cases were 7 GR, 4 MD, 4 SD and 4 deaths.
      Cases of severe subarachnoid hemorrhage with hematoma influenced the high death
      rate in direct surgery group. There were three complications associated with the
      procedure in the GDC group, however, the rate improved after advancement of the
      procedure. In conclusion, GDC treatment for ruptured cerebral aneurysm was
      satisfactorily acceptable compared to the results of direct surgery, however,
      more cases will be needed for precise comparison.

PMID- 20670570
TI  - Development of biologically active GDC for the treatment of cerebral aneurysms.
AB  - In Vitro Study: The surface of polystyrene dishes were treated either by: 1)
      collagen coating without ion implantation, or 2) collagen coating with ion
      implantation. Ne(+) implantation was performed on area 2 with fluences of 1 x
      10(15) at an energy of 150 keV Bovine endothelial cells were cultured on the
      dishes and the resistance to detachment of cells was evalated with trypsin
      treatment. Experimental Aneurysm Study: GDCs were coated with either type I
      collagen, fibronectin, vitronectin, laminin or fibrinogen. Ion implantation was
      then performed on these protein-coated GDCs. 56 experimental aneurysms were
      constructed microsurgically in the bilateral common carotid arteries of 28 swine.
      The aneurysms were embolized with standard GDCs or with ion-implanted protein
      coated GDCs. The animals were sacrificed at day 14 after coil placement. The
      aneurysmal orifice was observed microscopically. In vitro study showed that
      endothelial cell proliferation and strength of cell attachment were accerelated
      by ion implantation. On specimens examined 14 days post-embolization, greater
      fibrous tissue coverage at the neck of the aneurysm was observed macroscopically
      and microscopically with ion implanted GDCs, whereas only a fibrin-like thin
      layer covered the standard GDC surfaces. These in vitro and in vivo studied
      indicate that ion implantation combined with protein coating of GDCs improves
      cellular adhesion/proliferation. This technology may provide an improvement in
      clinical outcome of cerebral aneurysms.

PMID- 20670571
TI  - Modification of immediately electrically detachable coil.
AB  - An immediately electrically detachable coil (IEDC) that we previously developed
      was modified to enhance the reliability in its detachment system. IEDC is
      detached by applying a monopolar high-frequency electrical current that heat and
      disrupt a junction between a platinum coil and a delivery wire. The original IEDC
      immediately detaches only when the junction is just outside the catheter tip and
      precise positioning of the junction is required. In the modified IEDC, its
      delivery wire was insulated with poly tetra fluoroethylene (PTFE) to concentrate
      electrical current to the junction. The modified IEDC was tested in vitro and in
      animal experiments. Modified IEDC always detached instantaneously even when the
      junction was far beyond the catheter tip. Insulated delivery wire enabled the
      electrical current to be concentrated at the PVA junction and produce appropriate
      heat to disrupt the junction.

PMID- 20670572
TI  - Pre-embolization study of ruptured cerebral aneurysms with helical CT.
AB  - Sixteen ruptured aneurysms in 16 patients considered endovascular embolizations
      were examined. The findings of axial source images (axial images) and
      reconstructed three-dimensional CT angiography (3D-CTA) of helical CT were
      compared to those of rotational digital subtraction angiography (DSA). The
      aneurysmal neck and arterial branches adjacent to the neck were closely
      investigated. In seven out of 16 cases (43.8%), information provided by axial
      images and/or 3D-CTA was more useful than that of rotational DSA in evaluating
      the aneurysmal neck and arterial branches. Helical CT can provide valuable
      information on ruptured aneurysms that cannot be obtained by rotational DSA in
      some patients. This technique is useful to obtain anatomical information about
      aneurysms and to select the best therapeutic method.

PMID- 20670573
TI  - Long-term histopathology of intracranial aneurysms after endovascular treatment
      with coils. Report of two cases with ultrastructural evaluations by scanning
      electron microscopy.
AB  - We describe the results of electron microscopic examination in two patients with
      ruptured intracranial aneurysms who were successfully treated by endovascular
      coil embolization. The aneurysms were seen completely occluded on the follow-up
      angiograms. Autopsies of these patients were performed five and 26 months after
      endovascular treatment when they died of pneumonia and thalamic hemorrhage,
      respectively. The aneurysms were densely filled with the coils, which were
      readily identified through the thin and transparent wall of the aneurysmal dome.
      The orifice of the aneurysm was completely occluded so that macroscopically the
      coils were not directly visualized through the orifice. To examine any evidence
      of endothelialization across the orifice of the aneurysms, scanning electron
      microscopic examination was performed. In both cases, evidence of well
      regenerative endothelialization was observed across the aneurysmal orifice, being
      contiguous with the endothelial layer of the adjacent parent vessels. These
      ultrastructural findings indicate that the aneurysms are completely isolated from
      the lumen of the parent artery by a continuous lining of the regenerated
      endothelial cells following the endo vascular treatment with coils, and further
      suggest that aneurysms have a potential of being cured permanently by this
      treatment modality. This is, to the best of our knowledge, the first report in
      humans verifying a complete endothelialization of the luminal surface at the
      aneurysmal neck after coil embolization, as evidenced by scanning electron
      microscopy.

PMID- 20670574
TI  - Unstable mallet fractures: a comparison between three different techniques in a
      multicenter study.
AB  - OBJECTIVE: Management of mallet fractures is still a matter of discussion
      throughout the literature. For some authors, mallet fractures involving more than
      1/3 of the articular surface and palmar subluxation of the distal phalanx require
      surgical treatment. In this study we retrospectively compared three different
      techniques for mallet fractures: Kirschner wire fixation with extension block
      pinning (EBP) of the distal interphalangeal joint, Kirschner wires used as
      joysticks (KWJ) and interfragmentary mini-screws for open reduction and internal
      fixation (ORIF). METHODS: Fifty-eight mallet fractures with palmar subluxation in
      58 patients were treated with the aforementioned surgical techniques. Twenty
      mallet fractures in 20 patients 18 to 70 years old (average 42 years) were
      operated upon by EBP, 16 patients 22 to 56 years old (average 56 years) were
      operated upon using KWJ and 22 patients 22 to 54 years old (average 36 years)
      received ORIF. Follow-up time was 6 to 58 months (average 21 months). The
      following intraoperative parameters were considered: intraoperative time, number
      of Kirschner wires/screws and technical problems. Postoperative parameters
      included work absence and complications. The radiological evaluation was based on
      A-P and lateral views preoperatively and interviews at follow-up time. Bone union
      was defined by radiological evidence of bone trabeculae crossing the fracture
      site on at least one view. Clinical evaluation involved range of motion (ROM)
      test with a goniometer. Based on these measurements, a functional Crawford score
      was established. RESULTS: All fractures healed. In the KWJ group, intraoperative
      time was shorter and total ROM was wider (72 degree vs 58 degree and 54 degree;
      in the ORIF group, return to work was faster (2.7 weeks vs 7.2 weeks and 6 weeks)
      but a little higher complication rate due to screw positioning has been found.
      Functional results as to total ROM, distal interphalangeal lag extension and
      Crawford classification were similar. CONCLUSIONS: We demonstrate the advantages
      of the use of the three techniques and bone consolidation in all cases with no
      signs of osteoarthritis. Screw fixation is more technically demanding (longer
      intraoperative time and more complications) but allows earlier mobilization and
      faster returning to work. EBP and KWJ techniques are faster to perform with no
      complications but require a careful management of the pin tracts. There is no
      statistically significant difference as to functional results.

PMID- 20670575
TI  - Pedicle screw placement in the thoracic spine: a randomized comparison study of
      computer-assisted navigation and conventional techniques.
AB  - OBJECTIVE: To evaluate the accuracy of computer-assisted pedicle screw
      installation and its clinical benefit as compared with conventional pedicle screw
      installation techniques. METHODS: Total 176 thoracic pedicle screws placed in 42
      thoracic fracture patients were involved in the study randomly, 20 patients under
      conventional fluoroscopic control (84 screws) and 22 patients had screw insertion
      under three dimensional (3D) computer-assisted navigation (92 screws). The 2
      groups were compared for accuracy of screw placement, time for screw insertion by
      postoperative thin-cut CT scans and statistical analysis by X(2) test. The
      cortical perforations were then graded by 2-mm increments: Grade I (good, no
      cortical perforation), Grade II (screw outside the pedicle less than 2 mm), Grade
      III (screw outside the pedicle larger than 2 mm). RESULTS: In computer assisted
      group, 88 (95.65%) were Grade I (good), 4 (4.35%) were Grade II (less than 2mm),
      no Grade III (larger than 2 mm) violations. In conventional group, there were 14
      cortical violations (16.67%), 70 (83.33%) were Grade I (good), 11 (13.1%) were
      Grade II (less than 2 mm), and 3 (3.57%) were Grade III (larger than 2 mm)
      violations (P less than 0.001). The number (19.57%) of upper thoracic pedicle
      screws ( T(1)-T(4) ) inserted under 3D computer-assisted navigation was
      significantly higher than that (3.57%) by conventional fluoroscopic control (P
      less than 0.001). Average screw insertion time in conventional group was (4.56+/
      1.03) min and (2.54+/-0.63) min in computer assisted group (P less than 0.001).
      In the conventional group, one patient had pleura injury and one had a minor dura
      violation. CONCLUSIONS: This study provides further evidence that 3D computer
      assisted navigation placement of pedicle screws can increase accuracy, reduce
      surgical time, and be performed safely and effectively at all levels of the
      thoracic spine, particularly upper thoracic spine.

PMID- 20670576
TI  - Influences of head/neck ratio and femoral antetorsion on the safe-zone of
      operative acetabular orientations in total hip arthroplasty.
AB  - OBJECTIVE: To study the influences of head/neck ratio and femoral antetorsion on
      the safe-zone of operative acetabular orientations, which meets the criteria for
      desired range of motion (ROM) for activities of daily living in total hip
      arthroplasty (THA). METHODS: A three-dimensional generic, parametric and
      kinematic simulation module of THA was developed to analyze the cup safe-zone and
      the optimum combination of cup and neck antetorsion. A ROM of flexion > or =120
      degree internal rotation > or = 45 degree at 90 degree flexion, extension > or =
      30 degree and external rotation > or =40 degree was defined as the criteria for
      desired ROM for activities of daily living. The cup safe-zone was defined as the
      area that fulfills all the criteria of desired ROM before the neck impinged on
      the liner of the cup. For a fixed stem-neck (CCD)-angle of 130 degree theoretical
      safe-zones fulfilling the desired ROM were investigated at different general head
      neck ratios (GR=2, 2.17, 2.37, 2.61 and 2.92) and femoral anteversions (FA equal
      to 0 degree,10 degree,20 degree and 30 degree). RESULTS: Large GRs greatly
      increased the size of safe-zones and when the CCD-angle was 130 degree, a GR
      larger than 2.37 could further increase the size of safe-zones. There was a
      complex interplay between the orientation angles of the femoral and acetabular
      components. When the CCD-angle was 130 degree the optimum relationship between
      operative acetabular anteversion (OA) and femoral antetorsion (FA) could be
      estimated by the formula: OA equal to -0.80 multiply FA+47.06, and the minimum
      allowable operative acetabular inclination (OI(min)) would be more than 210.5
      multiply GR(-2.255). CONCLUSIONS: Large GRs greatly increase the size of safe
      zones and it is recommended that the GR be more than 2.37 so as to extend the
      acceptable range of error that surgeons cannot avoid completely during operation.
      As to the optimum operative acetabular inclination (OI), surgeons need to make a
      decision combining with other factors, including stress distribution, soft tissue
      and cup wear conditions, as well as patients'individual situations and demands.
      The data obtained from this study and the module of THA can be used to assist
      surgeons to choose and implant appropriate implants.

PMID- 20670577
TI  - Preliminary effect of proximal femoral nail antirotation on emergency treatment
      of senile patients with intertrochanteric fracture.
AB  - OBJECTIVE: To retrospectively analyse the clinical outcome of emergency treatment
      of senile intertrochanteric fractures with proximal femoral nail antirotation
      (PFNA). METHODS: From September 2008 to March 2009, 35 senile patients with
      intertrochanteric fracture, aged from 65 to 92 years with an average age of 76.5
      years, were treated with PFNA within 24 hours after injury. There were 10 type I
      fractures, 19 type II and 6 type III according to upgraded Evans-Jensen
      classification system. All patients were complicated with osteoporosis, and 19
      patients had preexisting internal medical diseases. According to the rating scale
      of disease severity by the American Society of Anesthesiologists (ASA), there
      were 9 grade I, 14 grade II, 8 grade III, and 4 grade IV. RESULTS: The duration
      for operation ranged from 45 to 73 minutes with an average of 57.6 minutes. The
      volume of blood loss during operation ranged from 50 to 120 ml with an average of
      77.5 ml. Patients could ambulate 2-4 days after operation (mean 3.5 days).
      Hospital stay was 4-7 days (mean 5.3 days). Full weight bearing time was 10-14
      weeks (mean 12.8 weeks). During hospitalization period, there was no regional or
      deep infection, hypostatic pneumonia, urinary tract infection and bedsore except
      for 2 cases of urine retention. All cases were followed up with an average period
      of 12.3 months, and bone healing achieved within 15-18 weeks (mean 16.6 weeks).
      No complications such as delayed union, coxa vara or coxa valga, screw breakage
      or backout occurred and only 2 cases had trochanter bursitis because of thin body
      and overlong end of the antirotated nail. According to the Harris grading scale,
      the results were defined as excellent in 21 cases, good in 9 cases and fair in 5
      cases, with the excellent and good rates of 85.7%. CONCLUSION: The emergency
      treatment of senile intertrochanteric fracture with proximal femoral nail
      antirotation has the advantages of minimal invasion, easy manipulation, less
      blood loss, shorter length of stay, less complications, and the preliminary
      clinical effect is satisfactory.

PMID- 20670578
TI  - Extremity fractures in children: a hospital based study in Tehran.
AB  - OBJECTIVE: Although long bone fracture in children is not life-threatening, it
      may cause major disability, loss of working days and severe psychological
      distress. We conducted this study to determine the pattern of extremity fracture
      due to trauma in children. METHODS: During one year in six general hospitals in
      Tehran, trauma patients who were hospitalized for more than 24 hours and
      sustained injuries within seven days before admission were included in the study.
      The records of children (< or = 16 years old) hospitalized in six general
      hospitals in Tehran due to trauma were reviewed prospectively. RESULTS: During
      the study period, 1 274 children had sustained extremity fractures. Male to
      female ratio was 3.6/1, with the mean age of (10.3+/-4.2) years. Falls and
      traffic crashes were the main causes of injuries, with the percentages of 57.3%
      and 37.1%, respectively. Simple fall (falling on the ground) consisted 60% of
      patients that sustained fall-related injuries. Pedestrians and bicycle riders
      comprised most of the cases that were injured due to traffic crashes. Of our
      cases, 56.8% sustained fractures in the upper extremities and 43.2% in the lower
      extremities. Forearm was the most common fracture site (34.1%). Comparing our
      results in preschool and school-age children, falls were the main cause of
      injuries in both groups, but fractures of lower extremities were significantly
      more common in preschool children. CONCLUSIONS: Improvement of physical condition
      of sidewalks and crossings in roads will be necessary for prevention of injuries.
      More attention to safety of home environment should be paid for control of
      preschools'injury at home. Education of children and adults is necessary to
      reduce injuries resulting from road traffic crashes.

PMID- 20670579
TI  - Design and biomechanical study of a modified pedicle screw.
AB  - OBJECTIVE: In pedicle screw fixation, the heads of monoaxial screws need to be
      directed in the same straight line to accommodate the rod placement by backing
      out during operation, which decreases the insertional torque and internal
      fixation strength. While polyaxial screws facilitate the assembly of the
      connecting rod, but its ball-in-cup locking mechanism reduces the static
      compressive bending yield strength as compared with monoaxial screws. Our study
      aimed to assess the mechanical performance of a modified pedicle screw. METHODS:
      In this study, the tail of the screw body of the modified pedicle screw was
      designed to be a cylinder-shaped structure that well matched the inner wall of
      the screw head and the screw head only rotated around the cyclinder. Monoaxial
      screws, modified screws and polyaxial screws were respectively assembled into 3
      groups of vertebrectomy models simulated by ultra high molecular weight
      polyethylene (UHMWPE) blocks. This model was developed according to a standard
      for destructive mechanical testing published by the American Society for Testing
      Materials (ASTM F1717-04). Each screw design had 6 subgroups, including 3 for
      static tension, load compression and torsion tests, and the rest for dynamic
      compression tests. In dynamic tests, the cyclic loads were 25%, 50%, and 75% of
      the compressive bending ultimate loads respectively. Yield load, yield ultimate
      load, yield stiffness, torsional stiffness, cycles to failure and modes of
      failure for the 3 types of screws were recorded. The results of modified screws
      were compared with those of monoaxial and polyaxial screws. RESULTS: In static
      tests, results of bending stiffness, yield load, yield torque and torsional
      stiffness indicated no significant differences between the modified and monoaxial
      screws (P > 0.05), but both differed significantly from those of polyaxial screws
      (P < 0.05). In dynamic compression tests, both modified and monoaxial screws
      showed failures that occurred at the insertion point of screw body into the
      UHMWPE block, while the polyaxial screw group showed screw body swung up and down
      the screw head because of loosening of the ball-in-cup mechanism. CONCLUSIONS:
      The modified screw is well-designed and biomechanically improved. And it can
      provide sufficient stability for segment fixation as monoaxial screws.

PMID- 20670580
TI  - Anatomic and radiological study on posterior pedicle screw fixation in the
      atlantoaxial vertebrae of children.
AB  - OBJECTIVE: To investigate the feasibility of posterior fixation with 3.5-mm
      pedicle screws in the atlantoaxial vertebrae of children. METHODS: In this study,
      atlantoaxial vertebrae specimens were obtained from 10 cadavers of children aged
      6-8 years. We measured the height and width of the C(1) pedicle and the
      midportion of C(1) lateral mass; the width of C(1) posterior arch under the
      vertebral artery groove and the height of the external and internal one-third of
      this part; the external, internal height and the superior, middle, inferior width
      of the C(2) pedicle (transverse foramen). Furthermore, computed tomography (CT)
      axial scan was performed on 20 age-matched volunteers to obtain relative data of
      their atlantoaxial vertebrae. We measured the length and width of the C(1) and
      C(2) pedicles in the atlantoaxial cross-sectional plane. On CT workstation, we
      also measured the angles between the longitudinal axes of the atlantoaxial
      pedicles and the midsagittal plane. RESULTS: For the cadaveric specimen group,
      the height and width of the C1 pedicle were (5.26+/-0.44) mm and (6.26+/-0.75) mm
      respectively. The height of the medial one-third of the C1 posterior arch under
      the vertebral artery groove was (4.07+/-0.24) mm. The external, internal height
      and superior, middle, inferior width of the C2 pedicle was (6.86+/-0.48) mm,
      (6.67+/-0.49) mm, (6.63+/-0.61) mm, (5.41+/-0.39) mm and (3.71+/-0.30) mm,
      respectively. For the volunteer group measured by CT scan, the height and width
      of the C(1) pedicle were (5.47+/-0.34) mm and (6.63+/-0.54) mm respectively,
      while (6.59+/-0.51) mm and (5.13+/-0.42) mm of the C2 pedicle. The angles between
      the atlas, axis pedicles and the midsagittal plane were (9.60+/-1.32) degree and
      (27.80+/-2.22) degree respectively. CONCLUSION: It is feasible to place a 3.5-mm
      pedicle screw in the C(1) and C(2) pedicles of children aged 6-8 years old.

PMID- 20670581
TI  - Comparative study of anterolateral approach versus posterior approach for total
      hip replacement in the treatment of femoral neck fractures in elderly patients.
AB  - OBJECTIVE: To compare the clinical outcome of anterolateral minimally invasive
      approach versus conventional posterior approach for total hip replacement against
      femoral neck fractures in elderly patients. METHODS: The retrospective study was
      carried out on 42 patients who suffered from displaced femoral neck fractures (19
      cases of Garden type III, 23 cases of Garden type IV) treated by total hip
      replacement via anterolateral minimally invasive approach or conventional
      posterior approach by the same experienced surgeon. The average age of the
      patients was 78.1 years (range: 65-89 years). They were divided into
      anterolateral mini-invasive group (22 cases) and posterior group (20 cases). The
      mean time of follow-up was 13 months (range: 6-36 months). The anterolateral
      approach described by Hardinge goes through between anterior 1/3 and posterior
      2/3 of the gluteus medius muscle, reaching the femoral neck from anterior
      capsule. The traditional posterior approach described by Moore (Southern
      incision) goes through the insertions of short external rotation muscles,
      reaching the femoral neck from posterior capsule. The related variables under
      observation were length of incision, operation time, postoperative limp, length
      of hospital stay and bed stay and dislolcation rate. RESULTS: The length of the
      skin incision varied between 7 cm and 12 cm with the anterolateral minimally
      invasive technique, compared to 15-22 cm in the conventional procedure. It took
      less time (average 15 minutes) to complete the anterolateral minimally invasive
      approach (72 min+/-15 min), compared with the conventional approach (87 min+/-10
      min). The average Harris hip score was 91.23+/-10.20 in anterolateral approach,
      90.03+/-11.05 in the posterior approach. The average length of hospital stay for
      patients with the anterolateral approach was (6.4+/-2.2) days (range: 4-9 days),
      while that in posterior approach was (9.2+/-3.1) days (range: 6-13 days). The
      average length of bed stay was (3.4+/-1.1) days (range: 2-5 days) in
      anterolateral group and (6.2+/-2.8) days (range: 3-10 days) in posterior group.
      No patients in anterolateral group experienced dislocation. One (5%) hip in
      posterior approach had dislocation. CONCLUSIONS: Anterolateral mini-invasive
      approach can decrease trauma, operation time, length of hospital stay and bed
      stay and rehabilitation time. The stability and minimal muscular damage permit
      the acceleration of postoperative rehabilitation, which can subsequently reduce
      the perioperative risk in the treatment of femoral neck fractures in the elderly
      undergoing total hip replacement.

PMID- 20670582
TI  - Interface contact profiles of a novel locking plate and its effect on fracture
      healing in goat.
AB  - OBJECTIVE: To evaluate the interface characteristics of the new-designed locking
      plate (LP) and limited contact-dynamic compression plate (LC-DCP) and compare the
      fracture healing between LP and LC-DCP in a goat tibia fracture model. METHODS:
      Eight-hole LP and LC-DCP were applied to fix fresh goat tibiae in a reproducible
      manner. The average pressure, force and interface contact area were calculated
      using Fuji prescale pressure sensitive film interposed among the plate and the
      bone and image analysis system. Eight-hole LP and LC-DCP were applied to each
      tibia in a goat tibia fracture model. The fracture healing was evaluated by X-ray
      photography at postoperative 8 weeks. The goats were sacrificed at postoperative
      12 weeks. Three-point bending test was conducted in the tibiae. RESULTS: The
      interface contact of LP system was smaller than that of LC-DCP (P < 0.05), while
      interface contact force of LP system was higher than that of LC-DCP (P < 0.05).
      Radiographs revealed that the fracture line disappeared in the LP group, while
      the fracture line was visible in DCP group at postoperative 8 weeks. At
      postoperative 12 weeks, the bending strength and bending load of fractured tibia
      were higher in LP group than in DCP group, respectively. CONCLUSION: The new
      designed locking plate can significantly decrease the contact area on the bone
      interface, which further provides better fracture healing than conventional
      plates.

PMID- 20670583
TI  - Arterial embolization for iatrogenic life-threatening bleeding from subcutaneous
      hypervascular tumor in prone position.
AB  - Performing angiography in the prone position is a difficult technique; however it
      is useful in some emergency situation. We experienced a 60 years old male who was
      performed lipoma excision on his back in his family doctor's clinic. Since
      massive arterial bleeding could not be controlled with manual astriction, he
      transferred to our hospital in prone position with hemodynamic instability.
      Operating field was not kept because of massive bleeding; therefore surgical
      treatment was impossible. We planed emergency arterial embolization (AE) in prone
      position. Hence we chose the left radial artery for vascular access. The left
      subclavicle arteriography showed many major and minor feeding arteries from left
      subclavicular and axillary arteries and a massive extravasation of the contrast
      medium. Three major feeding arteries were performed AE with gelatin sponge and
      steel coils. After AE, massive bleeding was controlled. He could discharge from
      our hospital on the 5th hospital day without any complication. Arterial
      embolization for life-threatening bleeding from subcutaneous hypervascular tumor
      in the prone position is first report to our knowledge, and it is extremely rare.
      However we thought that this technique is useful for patients who could not turn
      in the supine position, e.g. massive bleeding during renal biopsy and penetrating
      trauma from back.

PMID- 20670584
TI  - Neglected isolated fracture of the trochlea humeri.
AB  - A 15 years old girl was found to have isolated trochlea fracture 10 weeks after
      an injury caused by a fall on her left elbow. Movement of the elbow was severely
      restricted. Radiographs showed a half moon-shaped and anterosuperiorly displaced
      osteochondral fragment. Medial approach capsulotomy of the elbow and excision of
      the intraarticular adhesions were done to expose the isolated trochlea fracture.
      Headless screws were used for fixation, combined with bone grafting. The follow
      up showed union and excellent functional recovery of the elbow. Isolated trochlea
      fracture in adults is rare and usually associated with capitellar fractures
      and/or elbow dislocations. A neglected trochlea fracture is rarely reported in
      the English language literature to the best of our knowledge. Recognition of
      isolated trochlea fracture is vital to apprehend the pathomechanics of the injury
      and to devise a suitable treatment approach.

PMID- 20670585
TI  - Surgical vacuum-assisted closure for treatment of dramatic case of stonefish
      envenomation.
AB  - Skin necrosis of the foot, oedema and lymphangitis from stonefish (Synanceia
      verrucosa) sting are complications well known for a long time and with potential
      long-term sequelae. Literature reports of stonefish envenomation give no specific
      reference on soft tissue management and surgical reconstruction. This is the
      first report describing a case of foot stonefish envenomation treated by vacuum
      assisted closure therapy as an easy to use, accessible and simple adjuvant tool
      for management of large soft tissue necrosis.

PMID- 20670586
TI  - Acute subdural hematoma with swirl signs: clinical analysis of 15 cases.
AB  - From July 2003 to July 2009, 15 cases of subdural hematoma with swirl signs were
      treated in our hospital and their clinical data were retrospectively analysed.
      The mortality was compared between these patients and those with typical acute
      subdural hematoma who were treated at the same time in our hospital. Among the 15
      cases, full recovery was achieved in 4 cases, slight disability in 2, grave
      disability in 2 and death in 7 (46.7%). The mortality of these patients was
      conspicuously higher than that of typical subdural hematoma (14/83, 16.9%, P <
      0.01). Subdural hematoma with swirl signs is often suggestive of hazardous
      pathogenetic condition and early diagnosis and prompt surgical intervention is
      essential to reduce mortality.

PMID- 20670587
TI  - Acute traumatic subclavian artery thrombosis and its successful repair via
      resection and end-to-end anastomosis.
AB  - Subclavian artery thrombosis is a rare complication of clavicle fractures. We
      reported a 20-year-old man who was admitted to the emergency room after a road
      traffic accident. He was a pedestrian who was initially hit by a bus and after he
      fell down on the road, he was run over by a car. On evaluation, he was found to
      have multiple facial and rib fractures, distal right humerus and right clavicle
      fracture. Significantly, right radial pulse was absent. After further evaluation
      including Doppler studies and an angiography which revealed complete obstruction
      of right subclavian artery just distal to its 1st portion, the patient was
      urgently taken to the operation room. A midclavicular fracture was adjacent to
      the injured vessel. We established proximal and distal control, removed damaged
      part. After mobilizing the subclavian artery, an end-to-end anastomosis was made.
      Then open reduction and internal fixation of right distal humerus was performed.
      The rest of the postoperative course was unremarkable. To prevent complications
      of subclavian artery thrombosis, different treatment modalities can be used,
      including anticoagulation therapy, angioplasty, stenting and bypass procedures.

PMID- 20670588
TI  - [Rising incidence rates of schizophrenia among children and adolescents].
AB  - INTRODUCTION: The purpose was to expand the understanding of schizophrenia
      development in children and adolescents. An age- and gender-specific analysis of
      children and adolescents diagnosed with schizophrenia (F20.xx) was performed. The
      analysis included calculation of incidence rates of schizophrenia, schizophrenia
      subtypes, and an account of occurrence of any registered psychiatric diagnoses
      prior to first schizophrenia diagnosis. MATERIAL AND METHODS: Patients aged 0-21
      years diagnosed with schizophrenia (F20.xx) and registered in the Danish
      Psychiatric Central Research Register in 1994-2007 were included. RESULTS: The
      cohort consisted of 3,065 patients aged 6-21 years. Incidence rates vary with age
      and gender, and have been increasing in recent years. Boys have earlier onset and
      higher incidence rates than girls. The most common schizophrenia subtypes were
      paranoid (F20.0; 44.0%) and unspecified (F20.9; 28.7%). Three in every four
      patients had contact with the psychiatric hospital system prior to first
      schizophrenia diagnosis. CONCLUSION: Schizophreniform symptomatology tends to
      overlap with other psychiatric disorders, and diagnostic stability is low. The
      diagnosis schizophrenia should be systematically included in diagnostic
      deliberations. Qualitative studies describing and analysing early psychopathology
      in children and adolescents with schizophrenia will improve the present
      knowledge.

PMID- 20670589
TI  - [Urine samples from children collected in their homes].
AB  - INTRODUCTION: Children at high risk of urinary tract infection (UTI) enter a
      programme for domestic urine sampling at the Paediatric Department in Aarhus.
      Parents collect urine, describe symptoms and post the samples. We wanted to
      determine the value of domestic urine sampling and to evaluate the programme.
      MATERIAL AND METHODS: All samples received in 2004 were studied. RESULTS: A total
      of 706 urine samples from children in the programme were cultivated. In all 76
      children fulfilled the criteria for UTI when culture and symptoms were compared.
      Dip-slide analysis had a sensitivity of 72% and a negative predictive value of
      96%. A total of 329 urine samples with negative dip-slide analyses were collected
      from children with no urinary tract symptoms. Only 27 of these samples were
      culture-positive and none of these children developed signs of UTI. CONCLUSION:
      The results from this study suggest that home urine sampling from children at
      high risk of UTI with no symptoms does not contribute towards avoiding the
      development of pyelonephritis. A home urine sample analysis programme for
      children with symptoms is, however, a valuable instrument for early and efficient
      treatment of UTI in children with high risk of UTI. Urine samples should only be
      cultivated if the child has symptoms or the dip-slide test is positive.

PMID- 20670590
TI  - [Catecholaminergic polymorphic ventricular tachycardia is a rare inherited heart
      disease].
AB  - Catecholaminergic polymorphic ventricular tachycardia is a rare inherited heart
      disease, which can lead to life-threatening ventricular arrhythmias in patients
      with a structurally normal heart. The age of onset is usually between two and 12
      years and the initial symptom is frequently syncope or cardiac arrest. The
      arrhythmias are usually triggered by exercise or emotional affection. The
      diagnosis is often made using exercise electrocardiogram, which typically
      triggers arrhythmias. The treatment consists of beta blockers, frequently in
      combination with implantation of a cardioverter-defibrillator.

PMID- 20670591
TI  - [Nephrectomy through a single trocar incision].
AB  - Laparoendoscopic single-site surgery (LESS) is a laparoscopic technique in which
      a single small incision is made in the umbilicus with the use of a special device
      (single-port). We report the first nephrectomy performed in Scandinavia using
      this method. LESS nephrectomy is feasible, but requires a specific training
      programme comprising theory as well as practice. The authors believe that such
      training in conjunction with careful patient selection is essential.

PMID- 20670592
TI  - [Compartment syndrome in upper arm in anticoagulant therapy after minor trauma].
AB  - Compartment syndrome can be a complication of warfarin treatment after a minor
      trauma. We report a case of an elderly woman who had an uncontrolled, high
      Internationalised Normalized Ratio (INR) level and had incurred a large haematoma
      on the left upper arm after a fall. After two days, the patient developed a
      massive oedema and clinical compartment syndrome. It is essential to be aware of
      symptoms and signs of compartment ischaemia, as early fasciotomy can prevent late
      complications such as muscle necrosis and contracture or at worst amputation. The
      patient should be hospitalized for observation for compartment syndrome and
      control of the INR level.

PMID- 20670593
TI  - Prophylactic HPV vaccines: current knowledge of impact on gynecologic
      premalignancies.
AB  - Approaches for cervical cancer prevention are changing. Screening still remains
      the most effective method for cervical cancer prevention. Guidelines are moving
      to an older group of women to be screened less frequently with combinations of
      technologies that include biomarkers and cytology. HPV vaccination is an
      appropriate option for this older group of women as well, should the woman not
      wish to make her decision about vaccination until 21 years of age, the age of
      screening. Parents making decisions about HPV vaccination for their young
      adolescent daughters need to be fully informed that only continued screening
      prevents cervical cancer. HPV vaccination reduces the possibility of their
      daughter having an abnormal Pap test by 10% if the vaccines have not waned by the
      time the young adolescent becomes sexually active. HPV vaccine efficacy must last
      at least 15 years to contribute to the prevention of cervical cancers. At this
      time, protection against cervical intraepithelial neoplasia grade 2/3 (CIN 2/3)
      is 5 years for Gardasil and 8.4 years for Cervarix. The value of the current
      protection HPV vaccines offer will be viewed differently by different women.
      Physicians' ethical duties are to provide full explanation of the risks and
      benefits of adding HPV vaccination to the ongoing screening programs, and to
      support women in their personal choice for cervical cancer prevention.

PMID- 20670594
TI  - Hypusine: a new target for therapeutic intervention in diabetic inflammation.
AB  - Diabetes, a disorder of glucose homeostasis, has risen to near epidemic
      proportions world-wide and may be the single most important risk factor for
      cardiovascular, kidney, and eye disease. Dysfunction and destruction of islet
      beta cells, caused in part by the systemic or local release of pro-inflammatory
      cytokines, underlies all forms of diabetes. A major effort in diabetes research
      in recent years has been to identify new factors or pathways that can be
      therapeutically targeted to reduce cytokine action on the beta cell. Recent
      studies have suggested that an ancient and poorly understood protein, eIF5A, may
      be critical to cytokine release and signaling. Interestingly, eIF5A is the only
      protein to contain the unique amino acid hypusine, which is a polyamine-derived
      modification of amino acid lysine residue. This modification is catalyzed by the
      sequential actions of the inhibitable enzymes deoxyhypusine synthase and
      deoxyhypusine hydroxylase. Because the hypusine modification is absolutely
      required for eIF5A action in cytokine signaling, we propose that this
      modification could serve as a new drug target for islet beta cell protection in
      the setting of diabetic inflammation.

PMID- 20670595
TI  - Eradication of brain tumor stem cells with an oncolytic adenovirus.
AB  - Malignant gliomas, the most common type of primary brain tumors, are one of the
      most deadly cancers. Even when given the best available treatment, patients with
      these tumors face a poor prognosis, a situation that has changed little in the
      past several decades. Recently, researchers identified brain tumor stem cells
      that are responsible for tumors' resistance to therapy and recurrence. Since
      conventional radiotherapy and chemotherapy have had limited success in the
      treatment of malignant gliomas, we developed an oncolytic adenovirus, Delta-24
      RGD, that is able to efficiently eradicate both brain tumor bulk and stem cells,
      indicating its potential to induce complete tumor remission in patients with
      malignant gliomas. Currently, this novel agent is being tested in a phase I
      clinical trial at the Brain Tumor Center, The University of Texas MD Anderson
      Cancer Center.

PMID- 20670596
TI  - Predicting outcomes for children with neuroblastoma.
AB  - One of the main challenges in clinical cancer research remains to be accurate
      outcome prediction at the time of diagnosis. Although not frequent in absolute
      terms, neuroblastoma represents an important clinical challenge, as it is fatal
      in almost half of the patients despite advances in multimodal anti-cancer
      therapies. Four major risk stratification systems for neuroblastoma patients are
      currently being used in various parts of the world. Systems are based on a
      combination of various clinical, histopathological, and biological factors.
      Accordingly, different therapeutic schemes exist ranging from wait-and-see
      approaches to intensive multimodal therapies. Clinical experience with the
      currently used risk stratification systems suggests that the stratification of
      patients for treatment is useful, but patients with the same clinico-pathological
      parameters, receiving the same treatment, can have markedly different clinical
      courses. Therefore, the challenge remains to identify additional tumor-specific
      and sensitive prognostic markers for improved risk estimation at the time of
      diagnosis and to improve the choice of risk-related therapy. Various studies have
      put forward new prognostic markers, including copy number aberrations, gene
      expression signatures, and epigenetic markers.

PMID- 20670597
TI  - Neural potential of adipose stem cells.
AB  - In the last few years, adipose tissue, which has been largely ignored by
      anatomists and physicians for centuries, has found new brightness thanks to the
      stem cells contained within. These adipose derived stem cells (ADSC) have the
      same characteristics of the mesenchymal stem cells (MSC) residing in bone marrow.
      They have the same cell surface markers and are capable of differentiating into
      the same cell types, including osteoblasts, chondrocytes, myoblasts, adipocytes,
      and neuron-like cells. Adipose tissue is ubiquitous and uniquely expandable. Most
      patients possess excess fat that can be harvested, making adipose tissue the
      ideal large-scale source for research on clinical applications. In this review
      focused on the neural potential of adipose-derived stem cells. Current strategies
      for their isolation, differentiation, and in vitro characterization, as well as
      their latest in vivo applications for neurological disorders or injury repair,
      were discussed.

PMID- 20670598
TI  - Nuclear mode of the EGFR signaling network: biology, prognostic value, and
      therapeutic implications.
AB  - Epidermal growth factor receptor (EGFR) belongs to a large family of receptor
      tyrosine kinases that mediates many important physiological processes in both
      normal and cancerous cells. EGFR is best known for its classical role as a plasma
      membrane-bound receptor that, upon binding to its ligands, recruits and
      phosphorylates downstream molecules which subsequently regulate protein
      functions, protein-protein interactions, and gene expression. Built upon this
      traditional view of the EGFR pathway, a number of therapeutic agents have been
      developed aiming to target EGFR by blocking ligand-mediated receptor activation
      or by inhibiting its kinase activity. Unfortunately, most of these interventions
      have yielded disappointing clinical results in the majority of cancer types
      evaluated, with the exception of non-small cell lung cancer that carries specific
      EGFR mutants. Given the notion that these EGFR mutations are absent or very rare
      in other cancer types, extensive investigations have been directed at other
      potential mechanisms. Some of these efforts have led to rationales for EGFR-based
      combination regimens; however, they also demonstrated limited clinical benefits.
      In this review, we will focus on an emerging line of research that examines a
      novel mode of EGFR signaling that takes place in the cell nucleus. Specifically,
      we will outline the findings from a number of reports that have together
      established nuclear EGFR to be a functionally diversified molecule that regulates
      the biology of normal and malignantly transformed cells. In light of the fact
      that the impact of nuclear EGFR on anti-cancer therapy has recently developed
      into an area of intensive investigations, this review will also summarize the
      results of these investigations that suggest a potential role the nuclear EGFR
      may play in tumor response to radiation, chemotherapy, and EGFR-targeted therapy.

PMID- 20670599
TI  - GM-CSF-secreting vaccines for solid tumors: moving forward.
AB  - Cancer vaccines consisting of intact tumor cells genetically modified to secrete
      the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) have
      undergone extensive preclinical development. These vaccines induce the massive
      accumulation of dendritic cells at the intradermal injection site, which engulf,
      process, and present tumor antigens to activate tumor-specific T cells. Early
      phase clinical testing demonstrated promising evidence of safety and bioactivity,
      although initial phase III clinical trials were unsuccessful. Together, the
      preclinical and clinical data argue for the continued clinical development of
      these vaccines, integrating them with standard and novel cancer therapeutics that
      enhance vaccine activity by overcoming immune tolerance and suppression, and/or
      augmenting co-stimulatory pathways of T cell activation.

PMID- 20670600
TI  - Noroviruses: The leading cause of gastroenteritis worldwide.
AB  - Noroviruses are the leading cause of foodborne disease outbreaks worldwide, and
      may soon eclipse rotaviruses as the most common cause of severe pediatric
      gastroenteritis, as the use of rotavirus vaccines becomes more widespread.
      Genetic mutations and recombinations contribute to the broad heterogeneity of
      noroviruses and the emergence of new epidemic strains. Although typically a self
      limited disease, norovirus gastroenteritis can cause significant morbidity and
      mortality among children, the elderly, and the immunocompromised. The lack of a
      cell culture or small animal model has hindered norovirus research and the
      development of novel therapeutic and preventative interventions. However,
      vaccines based on norovirus capsid protein virus-like particles are promising and
      may one day become widely available through transgenic expression in plants.

PMID- 20670601
TI  - Genetics of systemic lupus erythematosus: contributions of mouse models in the
      era of human genome-wide association studies.
AB  - The past two years have brought great progress in the genetics of systemic lupus
      erythematosus (SLE) heralded by the publication of genome-wide association
      studies in humans and the identification of susceptibility genes in mouse models
      of spontaneous lupus. This influx of new information has revealed an ever
      increasing interdependence between the mouse and human systems for unraveling the
      genetic basis of lupus susceptibility. SLE is a complex disease in which defects
      in several functional pathways have been identified. Genetic variants in a number
      of genes in these pathways have now been directly associated with lupus in both
      species. These discoveries have lead to a better understanding of the mechanisms
      of disease, and offer potential novel target for therapeutic intervention. As a
      large number of susceptibility genes are identified, lupus genetics will focus on
      mechanistic and molecular studies, in which mouse models will continue to serve a
      pre-eminent role.

PMID- 20670602
TI  - Marginal zone B-cell lymphomas.
AB  - The term marginal-zone lymphoma (MZL) encompasses three closely related indolent
      B-cell non-Hodgkin's lymphoma subtypes, namely extranodal MZL or MALT lymphoma,
      nodal MZL, and splenic MZL. Although these neoplasms may share a common cell of
      origin, being the marginal zone B-cell, they display different characteristics
      with evident clinical and biological variations according to the organ where the
      lymphoma arises. The past 2 decades have spawned an avalanche of new data that
      encompasses the genetic aberrations and pathogenic mechanisms leading to these
      diseases. This article briefly addresses each of the MZL.

PMID- 20670603
TI  - The biology of melanoma prognostic factors.
AB  - Cutaneous melanoma still represents a paradox among all solid tumors. It is the
      cancer for which the best prognostic markers ever identified in solid tumors are
      available, yet there is very little understanding of their biological
      significance. This review focuses on recent biological data that shed light on
      the clinical-biological correlations underlining the 2010 American Joint
      Committee on Cancer (AJCC) melanoma staging system. A major challenge is to
      replace outcome clustering based on artificial biomarker breakpoints by a
      continuous multidimensional prognostic model. Major improvement will come from
      shared computerized tools that allow the generation of continuous likelihood
      scores for diagnosis, prognosis, and response prediction. This will lead to the
      development of platforms which can be used by scientists from different fields to
      integrate and share high-quality data in the pre-competitive setting and generate
      new probabilistic causal models.

PMID- 20670604
TI  - Potentiating the p53 network.
AB  - Expression of the p53 tumor suppressor, which has many roles in human biology, is
      altered in almost all cancers. It is a highly regulated sequence-specific
      transcription factor that is activated by a variety of cellular stresses
      including DNA damage. Central to its transactivation function as a master
      transcriptional regulator of hundreds of genes are the DNA target sequences bound
      by p53, where the canonical consensus target has generally been considered to be
      composed of two decameric half-sites (RRRCWWGYYY) separated by a variable spacer.
      Knowledge of p53 binding and transactivation at various p53 target sequences is
      important to understanding the biological role of this well-known "guardian of
      the genome." Recently we reported that both wild-type and mutant p53 can also
      drive transactivation at noncanonical half-site response elements (REs), a
      finding that greatly expands the universe of genes and regions potentially
      affected by p53. Furthermore, we found that p53-mediated transcription can be
      dramatically increased in conjunction with estrogen receptor (ER) transcription
      factors acting in cis at a nearby ER target sequence. Here we address the
      functionality of canonical and noncanonical REs in supporting transactivation by
      both wild-type and cancer-associated mutant p53s as well as transcriptional
      synergism of p53 with ER. Our findings have important implications for cellular
      and tissue responses to various stresses.

PMID- 20670605
TI  - Porcine monocyte subsets differ in the expression of CCR2 and in their
      responsiveness to CCL2.
AB  - Monocyte subsets have been shown to differ in the pattern of chemokine receptor
      expression and their migratory properties, both in human and mouse. Previously we
      have characterized in the swine several monocyte subpopulations, based on the
      expression of CD163, Tuk4 and SLA-II, which share features with the populations
      described in human and mouse. Here, we have analysed the expression of different
      chemokine receptors in the CD163-Tuk4+SLA-II- and CD163+Tuk4-SLA-II+ populations
      of porcine monocytes. CD163+Tuk4-SLA-II+ monocytes expressed higher CX3CR1 but
      lower CCR2 and CXCR4 mRNA levels than CD163-Tuk4+SLA-II- monocytes. Moreover,
      porcine CCL2 binding on Tuk4+SLA-II- but not on Tuk4-SLA-II+ cells was detected
      by using a CCL2-green fluorescence protein (pCCL2-GFP) fusion protein. Finally,
      flow cytometric analyses of monocytes recovered after chemotaxis assays show a
      clear increase in the proportion of Tuk4+SLA-II- cells in the fraction migrating
      toward CCL2, consistent with the polarized CCR2 expression in this monocyte
      population. The pattern of expression of these chemokine receptors reinforces the
      similarities of these porcine subsets with their human and mouse counterparts.

PMID- 20670606
TI  - In vivo, in vitro, and in silico analysis of methylation of the HIV-1 provirus.
AB  - HIV-1 latency is a barrier to overcome in the effort to fully eradicate the virus
      from infected individuals using highly active anti-retroviral therapy (HAART).
      Therefore, the study of the mechanisms underlying the establishment and
      maintenance of HIV-1 latency are vital to achieving a cure. Transcriptional
      repression of the viral promoter is the major cause of HIV-1 latency. DNA
      methylation of genomic regions known as CpG islands (CpGIs) is a well-established
      transcriptional regulatory mechanism, and the HIV-1 provirus contains several
      conserved CpGIs including two that are located within the viral promoter region.
      The study of these CpGIs in both in vitro and in vivo models of HIV-1 latency
      using the technique of bisulfite-mediated methylcytosine mapping has led to their
      identification as factors that contribute to the maintenance of HIV-1 latency.
      Here, we discuss the identification of CpGIs within the HIV-1 provirus and the
      study of their differential methylation patterns in several HIV-1 latency models
      using bisulfite-mediated methylcytosine mapping.

PMID- 20670608
TI  - Glycosaminoglycan-binding properties and kinetic characterization of human
      heparin cofactor II expressed in Escherichia coli.
AB  - Irreversible inactivation of alpha-thrombin (T) by the serpin, heparin cofactor
      II (HCII), is accelerated by ternary complex formation with the
      glycosaminoglycans (GAGs) heparin and dermatan sulfate (DS). Low expression of
      human HCII in Escherichia coli was optimized by silent mutation of 27 rare codons
      and five secondary Shine-Dalgarno sequences in the cDNA. The inhibitory
      activities of recombinant HCII, and native and deglycosylated plasma HCII, and
      their affinities for heparin and DS were compared. Recombinant and deglycosylated
      HCII bound heparin with dissociation constants (K(D)) of 6+/-1 and 7+/-1 microM,
      respectively, approximately 6-fold tighter than plasma HCII, with K(D) 40+/-4
      microM. Binding of recombinant and deglycosylated HCII to DS, both with K(D) 4+/
      1 microM, was approximately 4-fold tighter than for plasma HCII, with K(D) 15+/-4
      microM. Recombinant HCII, lacking N-glycosylation and tyrosine sulfation,
      inactivated alpha-thrombin with a 1:1 stoichiometry, similar to plasma HCII.
      Second-order rate constants for thrombin inactivation by recombinant and
      deglycosylated HCII were comparable, at optimal GAG concentrations that were
      lower than those for plasma HCII, consistent with its weaker GAG binding. This
      weaker binding may be attributed to interference of the Asn(169)N-glycan with the
      HCII heparin-binding site.

PMID- 20670609
TI  - Cyanogen bromide cleavage of proteins in salt and buffer solutions.
AB  - Protocols for recombinant polypeptide production should provide high yields and
      be efficient, user friendly, and time saving. To perform cyanogen bromide (CNBr)
      cleavage of fusion proteins, the majority of researchers first desalted and
      vacuum-dried samples and then dissolved them in aqueous formic or trifluoroacetic
      acid. We propose to exclude the desalting step and run CNBr cleavage directly. We
      show that the commonly used Tris-HCl, sodium phosphate, NaCl, imidazole, and
      guanidine-HCl do not interfere with the reaction under acidic conditions.
      Omitting the desalting step does not decrease the final yields of target
      products, as demonstrated for fusion proteins of different origin and
      composition.

PMID- 20670610
TI  - Microarray-driven validation of reference genes for quantitative real-time
      polymerase chain reaction in a rat vocal fold model of mucosal injury.
AB  - Relative quantification by normalization against a stably expressed reference
      gene is a widely used data analysis method in microarray and quantitative real
      time polymerase chain reaction (qRT-PCR) platforms; however, recent evidence
      suggests that many commonly utilized reference genes are unstable in certain
      experimental systems and situations. The primary aim of this study, therefore,
      was to screen and identify stably expressed reference genes in a well-established
      rat model of vocal fold mucosal injury. We selected and evaluated the expression
      stability of nine candidate reference genes. Ablim1, Sptbn1, and Wrnip1 were
      identified as stably expressed in a model-specific microarray dataset and were
      further validated as suitable reference genes in an independent qRT-PCR
      experiment using 2(-DeltaCT) and pairwise comparison-based (geNorm) analyses.
      Parallel analysis of six commonly used reference genes identified Sdha as the
      only stably expressed candidate in this group. Sdha, Sptbn1, and the geometric
      mean of Sdha and Sptbn1 each provided accurate normalization of target gene
      Tgfb1; Gapdh, the least stable candidate gene in our dataset, provided inaccurate
      normalization and an invalid experimental result. The stable reference genes
      identified here are suitable for accurate normalization of target gene expression
      in vocal fold mucosal injury experiments.

PMID- 20670611
TI  - Reliable resequencing of the human dystrophin locus by universal long polymerase
      chain reaction and massive pyrosequencing.
AB  - The X-linked dystrophin gene is well known for its involvement in Duchenne/Becker
      muscular dystrophies and for its exceptional megabase size. This locus at Xp21 is
      prone to frequent random molecular changes, including large deletions and
      duplications, but also smaller variations. To cope with such huge sequence
      analysis requirements in forthcoming diagnostic applications, we employed the
      power of the parallel 454 GS-FLX pyrosequencer to the dystrophin locus. We
      enriched the genomic region of interest by the robust amplification of 62
      fragments under universal conditions by the long-PCR protocol yielding 244,707 bp
      of sequence. Pooled PCR products were fragmented and used for library preparation
      and DNA sequencing. To evaluate the entire procedure we analyzed four male DNA
      samples for sequence coverage and accuracy in DNA sequence variation and for any
      potential bias. We identified 562 known variations and 55 additional variants not
      yet reported, among which we detected a causative Arg1844Stop mutation in one
      sample. Sanger sequencing confirmed all changes. Unexpectedly, only 3 x coverage
      was sufficient for 99.9993% accuracy. Our results show that long PCR combined to
      massive pyrosequencing is very reliable for the analysis of the biggest gene of
      the human genome and open the doors to other demanding applications in molecular
      diagnostics.

PMID- 20670612
TI  - The use of microRNAs as reference genes for quantitative polymerase chain
      reaction in soybean.
AB  - Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR)
      is a robust and widely applied technique used to investigate gene expression.
      However, for correct analysis and interpretation of results, the choice of a
      suitable gene to use as an internal control is a crucial factor. These genes,
      such as housekeeping genes, should have a constant expression level in different
      tissues and across different conditions. The advances in genome sequencing have
      provided high-throughput gene expression analysis and have contributed to the
      identification of new genes, including microRNAs (miRNAs). The miRNAs are
      fundamental regulatory genes of eukaryotic genomes, acting on several biological
      functions. In this study, miRNA expression stability was investigated in
      different soybean tissues and genotypes as well as after abiotic or biotic stress
      treatments. The present study represents the first investigation into the
      suitability of miRNAs as housekeeping genes in plants. The transcript stability
      of 10 miRNAs was compared to those of six previously reported housekeeping genes
      for the soybean. In this study, we provide evidence that the expression
      stabilities of miR156b and miR1520d were the highest across the soybean
      experiments. Furthermore, these miRNAs genes were more stable than the most
      commonly protein-coding genes used in soybean gene expression studies involving
      RT-qPCR.

PMID- 20670613
TI  - Enhanced immunoassay sensitivity using chemiluminescent acridinium esters with
      increased light output.
AB  - Chemiluminescent acridinium ester labels are widely used in clinical diagnostics
      especially in automated immunochemistry analyzers such as Siemens Healthcare
      Diagnostics' ADVIA Centaur systems. Although, chemiluminescence from acridinium
      compounds was discovered more than 50 years ago, details regarding the excitation
      process are still not well understood particularly in relation to acridinium
      structure and overall light output. Herein, we report an empirical study that
      correlates the presence of electron-donating methoxy groups at C-2 and/or C-7 in
      the acridinium ring with increased light output. We further demonstrate that
      these high light output labels can be combined with hydrophilic functional groups
      such as hexa(ethylene)glycol to generate unique acridinium esters that are stable
      and are useful in improving immunoassay sensitivity for both competitive and
      sandwich automated immunoassays.

PMID- 20670614
TI  - The carotenoid dioxygenase gene family in maize, sorghum, and rice.
AB  - Carotenoids and their apocarotenoid derivatives play essential physiological and
      developmental roles and provide plants tolerance to a variety of stresses.
      Carotenoid cleavage dioxygenases mediate the degradation of carotenoids to
      apocarotenoids. A better understanding of biosynthesis vs. degradation could be
      useful for controlling carotenoid levels leading to improved plant fitness and/or
      enhanced content of nutritionally valuable carotenoids. The Poaceae (grass) plant
      family contains many crops of agronomic value. Therefore this study focused on
      characterizing the carotenoid dioxygenase gene family in the grass species maize,
      rice, and sorghum with comparison made to newly identified gene families in two
      non-seed plants as well as an alga and previously identified eudicot genes.
      Genome analysis was used to map grass genes encoding the carotenoid dioxygenases
      to chromosome locations. Sequences of encoded proteins were phylogenetically
      compared. CCD8b was identified as a new class of cleavage dioxygenases that may
      play a specialized role in apocarotenoid biogenesis. A simple PCR assay was
      developed to measure CCD1 gene copy number which is known to vary in maize. Using
      a panel of maize inbred lines varying in carotenoid content, linear regression
      analysis revealed a statistically significant negative correlation between copy
      number of CCD1 and carotenoid content, an effect likely mediated through the
      resulting elevated levels of endosperm CCD1 transcripts in high copy number
      lines. The PCR assay adds to a growing toolbox for metabolic engineering of maize
      endosperm carotenoids. This new tool can be used to select maize lines that are
      less likely to promote endosperm carotenoid degradation, thus predicting optimal
      results in metabolic engineering of endosperm provitamin A and/or nonprovitamin A
      carotenoids.

PMID- 20670615
TI  - TGF-beta1 prevents up-regulation of the P2X7 receptor by IFN-gamma and LPS in
      leukemic THP-1 monocytes.
AB  - The P2X7 receptor is an extracellular ATP-gated cation channel critical in
      inflammation and immunity, and can be up-regulated by IFN-gamma and LPS. This
      study aimed to examine the effect of TGF-beta1 on the up-regulation of P2X7
      function and expression in leukemic THP-1 monocytes differentiated with IFN-gamma
      and LPS. Cell-surface molecules including P2X7 were examined by
      immunofluorescence staining. Total P2X7 protein and mRNA was assessed by
      immunoblotting and RT-PCR respectively. P2X7 function was evaluated by ATP
      induced cation dye uptake measurements. Cell-surface P2X7 was present on THP-1
      cells differentiated for 3days with IFN-gamma and LPS but not on undifferentiated
      THP-1 cells. ATP induced ethidium(+) uptake into differentiated but not
      undifferentiated THP-1 cells, and the P2X7 antagonist, KN-62, impaired ATP
      induced ethidium(+) uptake. Co-incubation of cells with TGF-beta1 plus IFN-gamma
      and LPS prevented the up-regulation of P2X7 expression and ATP-induced
      ethidium(+) uptake in a concentration-dependent fashion with a maximum effect at
      5ng/ml and with an IC(50) of ~0.4ng/ml. Moreover, ATP-induced YO-PRO-1(2+) uptake
      and IL-1beta release were abrogated in cells co-incubated with TGF-beta1. TGF
      beta1 also abrogated the amount of total P2X7 protein and mRNA induced by IFN
      gamma and LPS. Finally, TGF-beta1 prevented the up-regulation of cell-surface
      CD86, but not CD14 and MHC class II, by IFN-gamma and LPS. These results indicate
      that TGF-beta1 prevents the up-regulation of P2X7 function and expression by IFN
      gamma and LPS in THP-1 monocytes. This suggests that TGF-beta1 may limit P2X7
      mediated processes in inflammation and immunity.

PMID- 20670616
TI  - 3beta-hydroxylup-20(29)-ene-27,28-dioic acid dimethyl ester, a novel natural
      product from Plumbago zeylanica inhibits the proliferation and migration of MDA
      MB-231 cells.
AB  - Plumbago zeylanica, a traditional Indian herb is being used for the therapy of
      rheumatism and has been approved for anti-tumor activity. However, the molecular
      mechanisms involved in the biological action are not very well understood. In
      this study, the anti-invasive activities of P. zeylanica methanolic extract (PME)
      and pure compound 3beta-hydroxylup-20(29)-ene-27,28-dioic acid (PZP) isolated
      from it are investigated in vitro. PME and PZP were noted to have the ability to
      induce apoptosis as assessed by flow cytometry. Further, the molecular mechanism
      of apoptosis induced by PME and PZP was found by the loss of mitochondrial
      membrane potential with the down regulation of Bcl-2, increased expression of
      Bad, release of cytochrome c, activation of caspase-3 and cleavage of PARP
      leading to DNA fragmentation. Importantly, both PME and PZP were observed to
      suppress MDA-MB-231 cells adhesion to the fibronectin-coated substrate and also
      inhibited the wound healing migration and invasion of MDA-MB-231 cells through
      the reconstituted extracellular matrix. Gelatin zymography revealed that PME and
      PZP decreased the secretion of matrix metalloproteinases-2 (MMP-2) and
      metalloproteinases-9 (MMP-9). Interestingly both PME and PZP exerted an
      inhibitory effect on the protein levels of p-PI3K, p-Akt, p-JNK, p-ERK1/2, MMP-2,
      MMP-9, VEGF and HIF-1alpha that are consistent with the observed anti-metastatic
      effect. Collectively, these data provide the molecular basis of the anti
      proliferative and anti-metastatic effects of PME and PZP.

PMID- 20670617
TI  - Clinical and laboratory trends in fetal lung maturity testing.
AB  - BACKGROUND: The surfactant/albumin ratio is a popular fetal lung maturity (FLM)
      test that will be unavailable in the near future. We conducted surveys of
      obstetricians and clinical laboratorians to assess FLM testing trends from the
      perspectives of both disciplines and to identify how both communities might adapt
      to the loss of the surfactant/albumin ratio. METHODS: 2067 physicians were
      surveyed about their familiarity with and clinical utility of various FLM tests.
      6137 laboratorians were surveyed about their FLM test menu and volumes. RESULTS:
      Twenty-five percent of physicians indicated a decrease in FLM test ordering and
      the frequency of FLM testing has decreased significantly (p=0.011) since 1998.
      The surfactant/albumin ratio is the most frequently offered FLM test and was the
      test of choice for 62% of physicians. Without the surfactant/albumin ratio, 68%
      of physicians would order the lecithin/sphingomyelin ratio and 44% would order
      the lamellar body count (LBC) which were offered by 18 and 13% of laboratories,
      respectively. 16% of laboratories were planning to offer the LBC within 24
      months. CONCLUSIONS: FLM testing is decreasing. The loss of the
      surfactant/albumin ratio will increase the demand for the lecithin/sphingomyelin
      ratio and the LBC, yet few laboratories offer either test and most are not
      planning to offer the LBC.

PMID- 20670618
TI  - Distinct effects of carvone analogues on the isolated nerve of rats.
AB  - Carvone (p-mentha-6,8-dien-2-one) is a monoterpene ketone found as the main
      active component of various essential oils. It is obtained by distillation and
      occurs naturally as the enantiomers (+)- and (-)-carvone. Our group have shown
      that the in vivo antinociceptive activity of (-)-carvone is impaired with
      decreased nerve excitability. To better characterize the neuropharmacology of
      such a monoterpene, we investigated the profile of several carvone analogues to
      establish a structure-function relationship related to the compound action
      potential (CAP) inhibitory effect. We performed ex vivo assays to evaluate the
      effects of (+)- and (-)-carvone, carvacrol, (-)-carveol, and limonene on CAP
      characteristics using a modified single sucrose-gap method. Our results
      demonstrated that (-)-carvone was less potent (IC(50)=10.7+/-0.07 mM) in reducing
      nerve excitability than its enantiomer, (+)-carvone (IC(50)=8.7+/-0.1mM),
      although they shared a similar mode of action, since their effects were partially
      extinguished by nerve washing and also by reduction of depolarization velocity,
      probably as a result of voltage-gated sodium channel blockades. In a structure
      activity relationship study, we demonstrated that hydroxyl groups in the (-)
      carveol and carvacrol molecules enhanced the CAP blocking-effect, while the
      absence of oxygen moiety in (+)-limonene resulted in the effect being almost
      abolished. Therefore, inhibition of CAP conduction in peripheral nerves by
      monoterpenes could expand our understanding concerning the pharmacology of such
      natural bioactive compounds. Moreover, activation or inhibition of nerve
      excitability with these tested monoterpenes can be achieved by altering their
      chemical structures, and this can lead to further implications for target
      directed drug design.

PMID- 20670619
TI  - Metabolic regulation of coronary vascular tone: role of hydrogen peroxide,
      purinergic components, and angiotensin.
AB  - Metabolic regulation plays an important role in modifying coronary vascular tone.
      We hypothesized that hydrogen peroxide, purinergic components, and angiotensin,
      produced by cardiac myocytes control coronary vascular tone in proportion to
      metabolism. We measured changes in the diameter of isolated, pressurized coronary
      arterioles in response to supernatant from isolated cardiac myocytes in rats
      (stimulated for 20-, 60-, and 120-min at 400 bpm). Changes in the diameter of
      arterioles were determined under control conditions following treatment of
      arterioles with an adenosine receptor antagonist, 8-PSPT, a P2Y1 receptor
      antagonist, MRS-2179, or an angiotensin II receptor antagonist, olmesartan. A
      supernatant (500 microl to a 2 ml bath) from myocytes stimulated for 20-, 60- and
      120-min caused graded vasodilation (14.1+/-0.4, 20.2+/-1.6, 53.8+/-6.2%, P<0.01
      vs. non-stimulated, respectively). In 20-min stimulation, catalase with myocyte
      supernatants eliminated vasodilation. Following 60-min stimulation, catalase
      converted myocyte supernatant-induced vasodilation to a vasoconstriction (-15.1+/
      1.0%), and this vasoconstriction was eliminated by olmesartan. Upon 120-min
      stimulation, catalase partially reduced the vasodilation by myocyte supernatants
      (37.2+/-3.8%). The remaining vasodilation was converted to a vasoconstriction
      with 8-PSPT and MRS-2179, and this vasoconstriction was completely eliminated
      with olmesartan. Cardiac myocytes modulate vascular tone through the net effects
      of hydrogen peroxide, purinergic components (adenosine and ADP), and angiotensin
      in proportion to ischemia.

PMID- 20670620
TI  - Subthreshold pharmacological and genetic approaches to analyzing CaV2.1-mediated
      NMDA receptor signaling in short-term memory.
AB  - Ca(V)2.1 is highly expressed in the nervous system and plays an essential role in
      the presynaptic modulation of neurotransmitter release machinery. Recently, the
      antiepileptic drug levetiracetam was reported to inhibit presynaptic Ca(V)2.1
      functions, reducing glutamate release in the hippocampus, although the precise
      physiological role of Ca(V)2.1-regulated synaptic functions in cognitive
      performance at the system level remains unknown. This study examined whether
      Ca(V)2.1 mediates hippocampus-dependent spatial short-term memory using the
      object location and Y-maze tests, and perirhinal cortex-dependent nonspatial
      short-term memory using the object recognition test, via a combined
      pharmacological and genetic approach. Heterozygous rolling Nagoya (rol/+) mice
      carrying the Ca(V)2.1alpha(1) mutation had normal spatial and nonspatial short
      term memory. A 100mg/kg dose of levetiracetam, which is ineffective in wild-type
      controls, blocked spatial short-term memory in rol/+ mice. At 5mg/kg, the N
      methyl-D-aspartate (NMDA) receptor blocker (+/-)-3-(2-carboxypiperazin-4-yl)
      propyl-1-phosphonic acid (CPP), which is ineffective in wild-type controls, also
      blocked the spatial short-term memory in rol/+ mice. Furthermore, a combination
      of subthreshold doses of levetiracetam (25 mg/kg) and CPP (2.5mg/kg) triggered a
      spatial short-term memory deficit in rol/+ mice, but not in wild-type controls.
      Similar patterns of nonspatial short-term memory were observed in wild-type and
      rol/+ mice when injected with levetiracetam (0-300 mg/kg). These results indicate
      that Ca(V)2.1-mediated NMDA receptor signaling is critical in hippocampus
      dependent spatial short-term memory and differs in various regions. The
      combination subthreshold pharmacological and genetic approach presented here is
      easily performed and can be used to study functional signaling pathways in
      neuronal circuits.

PMID- 20670621
TI  - Some cardiovascular therapeutics inhibit paraoxonase 1 (PON1) from human serum.
AB  - Harel et al. (2004) report that atherosclerosis is the underlying cause for 50%
      of the mortality in Western societies, and organophosphates in nature constitute
      an important risk as well as a terrorist threat for all living things. Since
      paraoxonase enzyme (PON) is a bioscavenger against both atherosclerosis and
      organophosphate toxicity, studies on paraoxonase enzyme (PON) occupy an important
      place in the scientific world. In this study, we purified PON1 enzyme from human
      serum by using a simple three-step purification method: ammonium sulfate
      precipitation, ion-exchange chromatography and gel filtration chromatography. In
      addition, we investigated the effects of certain cardiovascular drugs on human
      serum paraoxonase enzyme activity. IC(50) values and K(i) constants were
      calculated for digoxin, metoprolol tartrate, verapamil, diltiazem, amiodarone,
      dobutamine, and methylprednisolone, which show inhibitory effects. IC(50) values
      were determined to be 0.012 microM, 0.621 microM, 0.672 microM, 1.462 microM,
      3.255 microM, 4.495 microM and 47.803 microM, respectively, and K(i) constants
      were calculated to be 0.035+/-0.01273 microM, 1.115+/-0.27003 microM, 1.188+/
      0.11529 microM, 3.104+/-1.00478 microM, 5.427+/-1.34063 microM, 10.7+/-3.14572
      microM and 109+/-17.47875 microM, respectively. A comparison of the IC(50) and
      K(i) values of the drugs revealed that digoxin has the maximum inhibition rate.
      Furthermore, methylprednisolone and amiodarone were found to be competitive
      inhibitors, verapamil and dobutamine were uncompetitive inhibitors, while others
      inhibited the enzyme in noncompetitive manner.

PMID- 20670622
TI  - Mechanisms of relaxant activity of the nitric oxide-independent soluble guanylyl
      cyclase stimulator BAY 41-2272 in rat tracheal smooth muscle.
AB  - The soluble guanylyl cyclase is expressed in airway smooth muscle, and agents
      that stimulate this enzyme activity cause airway smooth muscle relaxation and
      bronchodilation. The compound 5-Cyclopropyl-2-[1-(2-fluoro-benzyl)-1H
      pyrazolo[3,4-b]pyridin-3-yl]-pyrimidin-4-ylamine (BAY 41-2272) is a potent nitric
      oxide (NO)-independent soluble guanylyl cyclase stimulator, but little is known
      about its effects in airway smooth muscle. Therefore, this study aimed to
      investigate the mechanisms underlying the relaxations of rat tracheal smooth
      muscle induced by BAY 41-2272. Tracheal rings were mounted in 10-ml organ baths
      for isometric force recording. BAY 41-2272 concentration-dependently relaxed
      carbachol-precontracted tracheal rings (pEC(50)=6.68+/-0.14). Prior incubation
      with the NO synthesis inhibitor l-NAME (100 microM) or the soluble guanylyl
      cyclase inhibitor ODQ (10 microM) caused significant rightward shifts in the
      concentration-response curves to BAY 41-2272. Sodium nitroprusside caused
      concentration-dependent relaxations, which were greatly potentiated by BAY 41
      2272 and completely inhibited by ODQ. In addition, BAY 41-2272 shifted to the
      right the tracheal contractile responses to either carbachol (0.01-1 microM) or
      electrical field stimulation (EFS, 1-32 Hz). BAY 41-2272 (1 microM) also caused a
      marked rightward shift and decreased the maximal contractile responses to
      extracellular CaCl2, and such effect was not modified by pretreatment with ODQ.
      In addition, BAY 41-2272 (up to 1 microM) significantly increased the cGMP
      levels, and that was abolished by ODQ. Our results indicate that BAY 41-2272
      causes cGMP-dependent rat tracheal smooth muscle relaxations in a synergistic
      fashion with exogenous NO. BAY 41-2272 has also an additional mechanism
      independently of soluble guanylyl cyclase activation possibly involving Ca(2+)
      entry blockade.

PMID- 20670623
TI  - Protective effects of melatonin on testicular torsion/detorsion-induced ischemia
      reperfusion injury in rats.
AB  - Testicular torsion causes an enhanced formation of reactive oxygen species, which
      contributes to the pathophysiology of tissue damage. The aim of this study was to
      investigate the protective effect of melatonin on testicular torsion/detorsion
      induced ischemia-reperfusion (I/R) injury. A total of 24 male Wistar albino rats
      were divided into three groups of 8 animals each: control, I/R, and I/R treated
      with melatonin. The ischemia period was 5 h and orchiectomy was performed after 5
      h of detorsion. Melatonin (10 mg/kg, intraperitoneally [i.p.]) was administrated
      only once, 40 min prior to detorsion. Spermatogenesis and mean seminiferous
      tubule diameter (MSTD) were significantly decreased in the I/R groups were
      compared to the control group. Furthermore, the melatonin treated animals showed
      an improved histological appearance in the I/R group. Our data indicate a
      significant reduction in the activity of TUNEL; there was a rise in the
      expression of proliferating cell nuclear antigen (PCNA) and testosterone in
      testes tissue of the I/R group treated with melatonin therapy. Electron
      microscopy of the testes of the rats demonstrated that pretreatment with
      melatonin was particularly effective in preventing mitochondrial degeneration,
      dilatation of SER, and enlarged intercellular spaces in both Sertoli and
      spermatid cells in the I/R treated animals. We believe that further preclinical
      research into the utility of melatonin may indicate its usefulness as a potential
      treatment on testes injury after I/R in rats.

PMID- 20670624
TI  - Beneficial effects of sodium or ethyl pyruvate after traumatic brain injury in
      the rat.
AB  - Sodium pyruvate (SP) treatment initiated within 5 min post-injury is
      neuroprotective in a rat model of unilateral cortical contusion injury (CCI). The
      current studies examined: (1) effects of delayed SP treatments (1000 mg/kg, i.p.,
      at 1, 12 and 24h), (2) effects of single (1h) or multiple (1, 12 and 24h) ethyl
      pyruvate treatments (EP; at 20 or 40 mg/kg, i.p.), and (3) mechanisms of action
      for pyruvate effects after CCI. In Experiment 1, both SP and EP treatment(s)
      significantly reduced the number of dead/dying cells in the ipsilateral
      hippocampus (dentate hilus+CA3(c) and/or CA3(a-b) regions) at 72 h post-CCI.
      Pyruvate treatment(s) attenuated CCI-induced reductions of cerebral cytochrome
      oxidase activity at 7 2h, significantly improving activity in peri-contusional
      cortex after multiple SP or EP treatments. Optical density measures of
      ipsilateral CD11b immuno-staining were significantly increased 72 h post-CCI, but
      these measures of microglia activation were not different from sham injury values
      in SP and EP groups with three post-CCI treatments. In Experiment 2, three
      treatments (1, 12 and 24h) of SP (1000 mg/kg) or EP (40 mg/kg) significantly
      improved recovery of beam-walking and neurological scores in the first 3 weeks
      after CCI, and EP treatments significantly improved spatial working memory 1 week
      post-CCI. Ipsilateral CA3(b) neuronal loss, but not cortical tissue loss, was
      significantly reduced 1 month post-CCI with pyruvate treatments begun 1h post
      CCI. Thus, delayed pyruvate treatments after CCI are neuroprotective and improve
      neurobehavioral recovery; these effects may be mediated by improved metabolism
      and reduced inflammation.

PMID- 20670625
TI  - Maintenance of red blood cell integrity by AMP-activated protein kinase alpha1
      catalytic subunit.
AB  - AMP-activated protein kinase (AMPK) plays a pivotal role in regulating cellular
      energy metabolism. We previously showed that AMPKalpha1-/- mice develop moderate
      anemia associated with splenomegaly and high reticulocytosis. Here, we report
      that splenectomy of AMPKalpha1-/- mice worsened anemia supporting evidence that
      AMPKalpha1-/- mice developed a compensatory response through extramedullary
      erythropoiesis in the spleen. Transplantation of bone marrow from AMPKalpha1-/-
      mice into wild-type recipients recapitulated the hematologic phenotype. Further,
      AMPKalpha1-/- red blood cells (RBC) showed less deformability in response to
      shear stress limiting their membrane flexibility. Thus, our results highlight the
      crucial role of AMPK to preserve RBC integrity.

PMID- 20670626
TI  - Elevation of Kiss2 and its receptor gene expression in the brain and pituitary of
      grass puffer during the spawning season.
AB  - Kisspeptins are a family of neuropeptides encoded by Kiss1 and Kiss2 genes, and
      participate in neuroendocrine regulation of gonadotropin-releasing hormone (GnRH)
      secretion through activating their receptor, Kiss1r (or GPR54). Bioinformatic
      analyses have shown that there is a single gene for each kisspeptin (Kiss2) and
      its receptor (Kiss1r) in pufferfish, the function of which has yet to be
      elucidated. We cloned these two genes in grass puffer, which spawns on beach with
      semilunar cycles, and examined changes in their expression levels in the brain
      and pituitary at different reproductive stages over the spawning season. The
      Kiss2 precursor of 104 amino acid residues contains a putative kisspeptin peptide
      (SKFNLNPFGLRF). Kiss1r consists of 377 amino acid residues containing distinct
      characteristics of G-protein coupled receptors. Kiss2 and Kiss1r genes were
      expressed extensively in the brain, pituitary and gonads. The amounts of Kiss2
      and Kiss1r mRNAs were significantly elevated during the spawning period in the
      brain and pituitary of both sexes. There were strong positive correlations
      between the amounts of Kiss2 and Kiss1r mRNAs in the brain and pituitary over the
      spawning season. Significant positive correlations were also observed between the
      amounts of Kiss2/Kiss1r mRNAs and GnRH1 mRNA in the brain. The present results
      indicate that the Kiss2/Kiss1r system most probably plays an important role in
      the regulation of reproductive function in the spawning period of grass puffer,
      possibly through the stimulation of GnRH1 secretion. Furthermore, Kiss2 may have
      a local action in the pituitary.

PMID- 20670627
TI  - Continuous light and melatonin: daily and seasonal variations of brain binding
      sites and plasma concentration during the first reproductive cycle of sea bass.
AB  - The present study reports on the daily and seasonal variations in plasma
      melatonin concentration, and also in optic tectum and hypothalamus melatonin
      binding sites, in male European sea bass maintained under natural photoperiod
      (NP) or continuous light (LL) from early stages of development. Samples were
      collected on a 24-h cycle, at four physiological phases of their first annual
      reproductive cycle, i.e., pre-spermatogenesis, spermatogenesis, spermiation and
      post-spermiation. Under NP, (1) plasma melatonin levels were higher at night than
      during the day regardless of the year period, and the duration of the signal
      matched the duration of the dark phase; (2) daily variations in Kd and Bmax were
      found in the optic tectum, but only during spermiation, with the acrophase being
      180 degrees  out of phase with the plasma melatonin variations; and (3)
      significant seasonal Kd and Bmax changes were seen in the hypothalamus. Under LL,
      (1) plasma melatonin showed no elevation during the subjective night; and (2) Kd
      and Bmax exhibited seasonal variations in the hypothalamus. These results led to
      the conclusion that long-term exposure to LL affected both plasma melatonin and
      receptor oscillations; particularly, LL disrupted the receptor density circadian
      oscillation found in the optic tectum during spermiation under NP. This
      oscillation appears to be important for sea bass to pursue gametogenesis until
      full spermiation. The persistence of both daily and seasonal variation of
      receptor affinity and density in the hypothalamus under LL indicates that these
      variations are controlled by internal circadian and circannual clocks that do not
      involve melatonin.

PMID- 20670628
TI  - Trypanosoma cruzi I genotypes in different geographical regions and transmission
      cycles based on a microsatellite motif of the intergenic spacer of spliced-leader
      genes.
AB  - The intergenic region of spliced-leader (SL-IR) genes from 105 Trypanosoma cruzi
      I (Tc I) infected biological samples, culture isolates and stocks from 11 endemic
      countries, from Argentina to the USA were characterised, allowing identification
      of 76 genotypes with 54 polymorphic sites from 123 aligned sequences. On the
      basis of the microsatellite motif proposed by Herrera et al. (2007) to define
      four haplotypes in Colombia, we could classify these genotypes into four distinct
      Tc I SL-IR groups, three corresponding to the former haplotypes Ia (11
      genotypes), Ib (11 genotypes) and Id (35 genotypes); and one novel group, Ie (19
      genotypes). Genotypes harbouring the Tc Ic motif were not detected in our study.
      Tc Ia was associated with domestic cycles in southern and northern South America
      and sylvatic cycles in Central and North America. Tc Ib was found in all
      transmission cycles from Colombia. Tc Id was identified in all transmission
      cycles from Argentina and Colombia, including Chagas cardiomyopathy patients,
      sylvatic Brazilian samples and human cases from French Guiana, Panama and
      Venezuela. Tc Ie gathered five samples from domestic Triatoma infestans from
      northern Argentina, nine samples from wild Mepraia spinolai and Mepraia gajardoi
      and two chagasic patients from Chile and one from a Bolivian patient with
      chagasic reactivation. Mixed infections by Tc Ia+Tc Id, Tc Ia+Tc Ie and Tc Id+Tc
      Ie were detected in vector faeces and isolates from human and vector samples. In
      addition, Tc Ia and Tc Id were identified in different tissues from a heart
      transplanted Chagas cardiomyopathy patient with reactivation, denoting
      histotropism. Trypanosoma cruzi I SL-IR genotypes from parasites infecting
      Triatoma gerstaeckeri and Didelphis virginiana from USA, T. infestans from
      Paraguay, Rhodnius nasutus and Rhodnius neglectus from Brazil and M. spinolai and
      M. gajardoi from Chile are to our knowledge described for the first time.

PMID- 20670629
TI  - Hydrogen sulfide exposure increases desiccation tolerance in Drosophila
      melanogaster.
AB  - Hydrogen sulfide (H(2)S) has been shown to effect physiological alterations in
      several animals, frequently leading to an improvement in survival in otherwise
      lethal conditions. In the present paper, a volatility bioassay system was
      developed to evaluate the survivorship of Drosophila melanogaster adults exposed
      to H(2)S gas that emanated from a K(2)S donor. Using this bioassay system, we
      found that H(2)S exposure significantly increased the survival of flies under
      arid and food-free conditions, but not under humid and food-free conditions. This
      suggests that H(2)S plays a role in desiccation tolerance but not in nutritional
      stress alleviation. To further confirm the suggestion, the mRNA levels of two
      desiccation tolerance-related genes Frost and Desat2, and a starvation-related
      gene Smp-30, from the control and treated flies were measured by quantitative
      real-time PCR. These genes were up-regulated within 2h when the flies transferred
      to the arid and food-free bioassay system. Addition of H(2)S further increased
      Frost and Desat2 mRNA levels, in contrast to Smp-30. Thus, our molecular results
      were consistent with our bioassay findings. Because of the molecular and genetic
      tools available for Drosophila, the fly will be a useful system for determining
      how H(2)S regulates various physiological alterations.

PMID- 20670630
TI  - Induction of oviposition by injection of male-derived extracts in two
      Callosobruchus species.
AB  - In some insect species, certain substances in the seminal fluid of males induce
      egg production and laying in females. We determined the effects of male-derived
      substances on female oviposition behaviour in two Callosobruchus species, C.
      chinensis and C. maculatus. Aqueous extracts of the accessory gland; testis; and
      seminal vesicle, including the ejaculatory duct, were prepared. The injection of
      these extracts into abdomen of females induced oviposition in both species.
      Oviposition was induced by the testis and seminal vesicle extracts in C.
      chinensis and by the accessory gland extracts in C. maculatus. The extracts were
      separated into three fractions by ultrafiltration: fractions I, molecular weight
      (MW) <3 kDa; fraction II, 3-14 kDa; and fraction III, >14 kDa. Fraction III
      induced oviposition in both species. These results suggest that in these two
      species, the substances that induce oviposition have similar MW but are present
      in different organs. Oviposition was induced by high-MW (>14 kDa) substances in
      the testis and seminal vesicle in C. chinensis, and by high-MW substances in
      accessory gland in C. maculatus. Here, we have discussed the relationship between
      oviposition and the abovementioned male-derived substances.

PMID- 20670631
TI  - Host-parasite relationship of the geoduck Panopea abbreviata and the green alga
      Coccomyxa parasitica in the Argentinean Patagonian coast.
AB  - The association of the geoduck Panopea abbreviata and the green alga Coccomyxa
      parasitica is described. The identity of the green alga was confirmed by
      molecular studies; the alga was found within the hemocytes that infiltrate the
      connective tissue of the geoduck siphons. Cytological characteristics of
      hemocytes were not altered by algal infection; very often the algae were seen
      enveloped by a digestive vacuole within the hemocyte cytoplasm, evidencing
      diverse degrees of resorption. Connective cells of siphons were rarely infected
      by C. parasitica. The mean prevalence of C. parasitica was higher (82%) in San
      Matias Gulf (42 degrees 00'S, 65 degrees 05'W) than in San Jose Gulf (45%) (40
      degrees 32'S, 64 degrees 02'W); except for spring, when the two locations showed
      no differences in prevalences (80%). Independently of location, season and host
      size, infected geoducks showed lower condition index values than uninfected ones.
      Regarding other bivalve species, only one specimen of the razor clam Ensis macha
      was found infected, and none of the oysters Ostrea puelchana and Pododesmus rudis
      and scallop Aequipecten tehuelchus was parasitized by the green alga.

PMID- 20670632
TI  - Static behavioral effects on gonorrhea transmission dynamics in a MSM population.
AB  - An SIS/SAS model of gonorrhea transmission in a population of highly active men
      having-sex-with-men (MSM) is presented in this paper to study the impact of safe
      behavior on the dynamics of gonorrhea prevalence. Safe behaviors may fall into
      two categories-prevention and self-awareness. Prevention will be modeled via
      consistent condom use and self-awareness via STD testing frequency. Stability
      conditions for the disease free equilibrium and endemic equilibrium are
      determined along with a complete analysis of global dynamics. The control
      reproductive number is used as a means for measuring the effect of changes to
      model parameters on the prevalence of the disease. We also find that appropriate
      intervention would be in the form of a multifaceted approach at overall risk
      reduction rather than tackling one specific control individually.

PMID- 20670634
TI  - C-reactive protein triggers inflammatory responses partly via TLR4/IRF3/NF-kappaB
      signaling pathway in rat vascular smooth muscle cells.
AB  - AIMS: C-reactive protein (CRP) plays an important role in the inflammatory
      process of atherosclerosis. Toll-like receptor 4 (TLR4) participates in
      atherogenesis by mediating the inflammatory responses. The aim of this experiment
      was to investigate the pro-inflammatory effects and mechanisms of CRP in rat
      vascular smooth muscle cells (VSMCs), especially focusing on the effects of CRP
      on IL-6 and peroxisome proliferator-activated receptor gamma (PPARgamma), and
      TLR4-dependent signal pathway. MAIN METHODS: rat VSMCs were cultured, and CRP was
      used as a stimulant for IL-6 and peroxisome proliferator-activated receptor gamma
      (PPARgamma). IL-6 level in the culture supernatant was measured by ELISA, and
      mRNA and protein expressions were assayed by quantitative real-time PCR and
      western blot, respectively. RNA interference was used to assess the roles of TLR4
      and interferon regulatory factor 3 (IRF3) in the pro-inflammatory signal pathway
      of CRP. KEY FINDINGS: CRP stimulated IL-6 secretion, and inhibited mRNA and
      protein expression of PPARgamma in VSMCs in a concentration-dependent manner.
      Additionally, CRP induced TLR4 expression, promoted nuclear translocation of NF
      kappaB (p65), and augmented IkappaBalpha phosphorylation in VSMCs. Taken
      together, CRP induces the inflammatory responses through increasing IL-6
      generation and reducing PPARgamma expression in VSMCs, which is mediated by
      TLR4/IRF3/NF-kappaB signal pathway. SIGNIFICANCE: CRP is able to stimulate IL-6
      production and to inhibit PPARgamma expression in VSMCs via MyD88-independent
      TLR4 signaling pathway (TLR4/IRF3/NF-kappaB). These provide the novel evidence
      for the pro-inflammatory action of CRP involved in atherogenesis.

PMID- 20670633
TI  - Extracellular matrix roles during cardiac repair.
AB  - The cardiac extracellular matrix (ECM) provides a platform for cells to maintain
      structure and function, which in turn maintains tissue function. In response to
      injury, the ECM undergoes remodeling that involves synthesis, incorporation, and
      degradation of matrix proteins, with the net outcome determined by the balance of
      these processes. The major goals of this review are a) to serve as an initial
      resource for students and investigators new to the cardiac ECM remodeling field,
      and b) to highlight a few of the key exciting avenues and methodologies that have
      recently been explored. While we focus on cardiac injury and responses of the
      left ventricle (LV), the mechanisms reviewed here have pathways in common with
      other wound healing models.

PMID- 20670635
TI  - Monitoring homologous recombination in rice (Oryza sativa L.).
AB  - Here we describe a system to assay homologous recombination during the complete
      life cycle of rice (Oryza sativa L.). Rice plants were transformed with two
      copies of non-functional GUS reporter overlap fragments as recombination
      substrate. Recombination was observed in all plant organs examined, from the seed
      stage until the flowering stage of somatic plant development. Embryogenic cells
      exhibited the highest recombination ability with an average of 3x10(-5)
      recombination events per genome, which is about 10-fold of that observed in root
      cells, and two orders of that observed in leaf cells. Histological analysis
      revealed that recombination events occurred in diverse cell types, but
      preferentially in cells with small size. Examples of this included embryogenic
      cells in callus, phloem cells in the leaf vein, and cells located in the root
      apical meristem. Steady state RNA analysis revealed that the expression levels of
      rice Rad51 homologs are positively correlated with increased recombination rates
      in embryogenic calli, roots and anthers. Finally, radiation treatment of
      plantlets from distinct recombination lines increased the recombination frequency
      to different extents. These results showed that homologous recombination
      frequency can be effectively measured in rice using a transgene reporter assay.
      This system will facilitate the study of DNA damage signaling and homologous
      recombination in rice, a model monocot.

PMID- 20670636
TI  - High incidence of 'synaesthesia for pain' in amputees.
AB  - Synaesthesia for pain is a phenomenon where a person experiences pain when
      observing or imagining another in pain. Anecdotal reports of this type of
      experience have most commonly occurred in individuals who have lost a limb.
      Distinct from phantom pain, synaesthesia for pain is triggered specifically in
      response to pain in another. Here, we provide the first preliminary investigation
      into synaesthesia for pain in amputees to determine the incidence and
      characteristics of this intriguing phenomenon. Self-referring amputees (n=74)
      answered questions on synaesthesia for pain within a broader survey of phantom
      pain. Of the participants, 16.2% reported that observing or imagining pain in
      another person triggers their phantom pain. Further understanding of synaesthesia
      for pain may provide a greater insight to abnormal empathic function in clinical
      populations as well as therapeutic intervention for at risk groups.

PMID- 20670638
TI  - Individual aggressiveness in the crab Chasmagnathus: Influence in fight outcome
      and modulation by serotonin and octopamine.
AB  - In a previous work we found that size-matched Chasmagnathus crabs establish
      winner-loser relationships that were stable over successive encounters but no
      evidence of escalation was revealed through fights. Here, we evaluated the
      hypothesis that size-matched fights between these crabs would be resolved
      according to the contestants' level of aggressiveness. Moreover, we aim at
      analysing the proximate roots of aggression, addressing the influence of the
      biogenic amines serotonin (5HT) and octopamine (OA) in crab's agonistic
      behaviour. To achieve these purposes, the following experiments were carried out.
      First, we performed successive fight encounters between the same opponents,
      varying the number of encounters and the interval between them, to assess the
      stability and progression of the winner-loser relationship. Then, we analysed
      dominance relationships in groups of three crabs, evaluating the emergence of
      linearity. Thirdly, we examined the effects of 5HT and OA injections over the
      fight dynamics and its result. Our findings show that contest outcome is
      persistent even through four encounters separated by 24h, but a comparison
      between encounters does not reveal any saving in fight time or increase in the
      opponent disparity. Within a group of crabs, a rank-order of dominance is
      revealed which is reflected in their fight dynamics. Interestingly, these results
      would not be due to winner or loser effects, suggesting that fight outcome could
      be mainly explained as resulting from differences in the level of aggressiveness
      of each opponent. Moreover, this individual aggressiveness can be modulated in
      opposite directions by the biogenic amines 5HT and OA, being increased by 5HT and
      decreased by OA.

PMID- 20670637
TI  - Role of melanin-concentrating hormone in the control of ethanol consumption:
      Region-specific effects revealed by expression and injection studies.
AB  - The peptide melanin-concentrating hormone (MCH), produced mainly by cells in the
      lateral hypothalamus (LH), perifornical area (PF) and zona incerta (ZI), is
      suggested to have a role in the consumption of rewarding substances, such as
      ethanol, sucrose and palatable food. However, there is limited information on the
      specific brain sites where MCH acts to stimulate intake of these rewarding
      substances and on the feedback effects that their consumption has on the
      expression of endogenous MCH. The current study investigated MCH in relation to
      ethanol consumption, in Sprague-Dawley rats. In Experiment 1, chronic consumption
      of ethanol (from 0.70 to 2.7 g/kg/day) dose-dependently reduced MCH gene
      expression in the LH. In Experiments 2-4, the opposite effect was observed with
      acute oral ethanol, which stimulated MCH expression specifically in the LH but
      not the ZI. In Experiment 5, the effect of MCH injection in brain-cannulated rats
      on ethanol consumption was examined. Compared to saline, MCH injected in the
      paraventricular nucleus (PVN) and nucleus accumbens (NAc) selectively stimulated
      ethanol consumption without affecting food or water intake. In contrast, it
      reduced ethanol intake when administered into the LH, while having no effect in
      the ZI. These results demonstrate that voluntary, chronic consumption of ethanol
      leads to local negative feedback control of MCH expression in the LH. However,
      with a brief exposure, ethanol stimulates MCH-expressing neurons in this region,
      which through projections to the feeding-related PVN and reward-related NAc can
      promote further drinking behavior.

PMID- 20670640
TI  - Is gender difference in postnatal thyroid growth associated with specific
      expression patterns of androgen and estrogen receptors?
AB  - Variations in sex steroids bioavailability were linked to the gender difference
      in the growth of thyroid glands of neonatal rats. In the present study we tested
      androgen receptor (AR) and estrogen receptor (ER) concentrations by ligand
      binding assay, and expression of their genes by RT-PCR and Western blot in the
      thyroid glands of neonatal rats. AR concentration remained elevated from
      postnatal day (PND) 10 onwards in males, whereas it decreased by PND 20 in
      females. AR mRNA and protein expressions were higher in males than females, which
      increased by PND 10, decreased after PND 15 and reached the nadir by PND 20. ER
      concentration increased by PND 10 and decreased thereafter in both sex. ERalpha
      mRNA expression diminished by PND 15 in both sex; while ERbeta mRNA decreased by
      PND 15 to reach the nadir by PND 20 in males, it was augmented by PND 10 in
      females to reach the peak by PND 15 and diminished by PND 20. ERalpha protein
      expression increased by PND 10 and remained elevated till PND 20 in both sex.
      ERbeta protein expression in males increased by PND 10 and decreased by PND 20,
      while it remained static up to PND 15 and decreased in females. Testosterone
      stimulated [(3)H]-thymidine uptake and the expression of IGF-1 and NIS genes in
      thyrocytes of both sex in vitro, while estradiol stimulated them in females but
      not in males. We conclude that androgens influence the growth and differentiation
      of thyrocytes through augmented expression of AR, IGF-1 and NIS in either sex,
      whereas estrogen imparts the gender difference, which may be at a level beyond
      the expression of ERs.

PMID- 20670639
TI  - Diet choice, cortisol reactivity, and emotional feeding in socially housed rhesus
      monkeys.
AB  - Chronic psychosocial stress produces an array of adverse health consequences that
      are highly comorbid, including emotional eating, affective disorders, and
      metabolic syndrome. The consumption of high caloric diets (HCDs) is thought to
      provide comfort in the face of unrelenting psychosocial stress. Using social
      subordination in female rhesus monkeys as a model of continual exposure to daily
      stressors in women, we tested the hypothesis that subordinate females would
      consume significantly more calories from a HCD compared to dominant females, and
      this pattern of food intake would be associated with reduced cortisol release and
      reduced frequency of anxiety-like behaviors. Food intake, parameters of cortisol
      secretion, and socio-emotional behavior were assessed for 3 weeks during a no
      choice phase when only a low caloric diet (LCD) was available and during a choice
      condition when both a LCD and HCD were available. While all animals preferred the
      HCD, subordinate females consumed significantly more of the HCD than did dominant
      females. A flattening of the diurnal cortisol rhythm and a greater increase in
      serum cortisol to an acute social separation occurred during the diet choice
      condition in all females. Furthermore, the rate of anxiety-like behavior
      progressively declined during the 3-week choice condition in subordinate but not
      dominant females. These data provide support for the hypothesis that daily
      exposure to psychosocial stress increases consumption of calorically dense foods.
      Furthermore, consumption of HCDs may be a metabolic stressor that synergizes with
      the psychosocial stress of subordination to further increase the consumption of
      these diets.

PMID- 20670641
TI  - Structure, function and evolution of three-finger toxins: mini proteins with
      multiple targets.
AB  - Snake venoms are complex mixtures of pharmacologically active peptides and
      proteins. These protein toxins belong to a small number of superfamilies of
      proteins. Three-finger toxins belong to a superfamily of non-enzymatic proteins
      found in all families of snakes. They have a common structure of three beta
      stranded loops extending from a central core containing all four conserved
      disulphide bonds. Despite the common scaffold, they bind to different
      receptors/acceptors and exhibit a wide variety of biological effects. Thus, the
      structure-function relationships of this group of toxins are complicated and
      challenging. Studies have shown that the functional sites in these 'sibling'
      toxins are located on various segments of the molecular surface. Targeting to a
      wide variety of receptors and ion channels and hence distinct functions in this
      group of mini proteins is achieved through a combination of accelerated rate of
      exchange of segments as well as point mutations in exons. In this review, we
      describe the structural and functional diversity, structure-function
      relationships and evolution of this group of snake venom toxins.

PMID- 20670642
TI  - Effects of the mycotoxin destruxin A on Locusta migratoria visceral muscles.
AB  - Destruxins, a family of cyclic peptides, are produced by various species of
      entomopathogenic fungi. These peptides have been shown to influence calcium
      dependent processes in insect cell lines and tissues, such as skeletal muscles.
      To better understand the mechanism of action of these peptide toxins on insect
      muscular tissues, we have evaluated the effects of destruxin A on the
      contractions of oviducts and hindgut of Locusta migratoria. In oviducts,
      destruxin A increased the frequency of spontaneous contractions and induced a
      dose-dependent tonic contraction; the EC(50) for lower lateral and upper lateral
      oviducts was 0.7 microM and 8.7 microM, respectively. In hindgut, destruxin A
      also caused an increase in the frequency of spontaneous contractions; the EC(50)
      was 3.2 microM. The action of destruxin A was abolished in Ca(2+)-free saline or
      when the Ca(2+) channel blocker CoCl(2) was added to the incubation saline.
      Likewise, the presence of 50 microM nifedipine or 100 microM verapamil in the
      medium reduced the magnitude of destruxin A's effect, particularly in hindgut.
      The depolarization of muscle membranes by 100 mM K(+) saline prevented the action
      of destruxin A. Preincubation of lower lateral oviducts in the intracellular
      Ca(2+) antagonist TMB-8 did not have any effect on destruxin A action; however,
      preincubation in the calmodulin inhibitor trifluoperazine greatly reduced the
      effect of destruxin A. Taken together, these results show that destruxin A has an
      excitatory effect on contractions of insect visceral muscles of L. migratoria.
      Destruxin A-induced contractions appear to be dependent on extracellular, but not
      on intracellularly-released Ca(2+), which suggest that this peptide toxin might
      be acting on insect visceral muscle by facilitating an influx of extracellular
      Ca(2+).

PMID- 20670643
TI  - Spectroscopic studies on the pH-dependent structural dynamics of gamma-conglutin,
      the blood glucose-lowering protein of lupin seeds.
AB  - gamma-Conglutin is a blood glucose-lowering protein purified from lupin (Lupinus
      albus, L.) seed. Despite various features of this protein have already been
      studied, no function in the seed nor any mechanism of action as a hypoglycemic
      nutraceutical compound have been identified so far. The lupin protein was shown
      to exist both in monomeric and multimeric forms as a function of pH. However, a
      detailed description of the pH-dependent structural dynamics of this protein, as
      the basis to investigate the reason/s of its functional behaviour, is not
      available yet. In this study, multiple and independent spectroscopic approaches,
      including light scattering associated to size exclusion chromatography of both
      untreated and covalently cross-linked protein, near and far UV circular
      dichroism, intrinsic and extrinsic fluorescence measurements, have been used to
      monitor oligomeric and conformational modifications caused by pH changes.
      Altogether, the results revealed a tetramer-dimer-monomer transition between
      neutral to slightly acidic pH and a dramatic and abrupt conformational change
      below pH 3.5. According to these findings, a model depicting gamma-conglutin
      structural dynamics was drawn. This model highlights the primary role of amino
      acid side group electrostatic interactions in the oligomer
      association/dissociation equilibria and in the pH-driven collapse of the native
      conformation.

PMID- 20670644
TI  - The relationship between dose-dependent antitussive and bronchodilatory effects
      of Opilia celtidifolia polysaccharide and nitric oxide in guinea pigs.
AB  - A crude polysaccharide composed of uronic acids (32%), arabinose (26%), glucose
      (15%), galactose (11%), rhamnose (7%), mannose (5%), xylose (4%) and small amount
      of fucose residues has been isolated from the leaves of Opilia celtidifolia by
      boiled water extraction. Chemical analyses of Opilia polysaccharide revealed the
      prevalence of a pectin material with high arabinose and galacturonic acid
      contents. Opilia polysaccharide showed significant biological effects on
      chemically induced cough reflex and reactivity of airways smooth muscle in vitro
      and in vivo conditions in guinea pigs test system. Tests confirmed the dose
      dependent cough-suppressive effect of Opilia polysaccharide comparable with
      activity of centrally acting codeine. Further, the bronchodilatory tests resulted
      in significant decrease in the values of specific airway resistance, which is
      very sensitive predictor of airway smooth muscle reactivity in vivo conditions
      regardless of bronchoconstricting mechanism. The results of in vitro experiments
      confirmed not only the bronchodilatory effect Opilia polysaccharide but revealed
      that its bronchodilatory mechanism is partially accompanied with enhanced NO
      production.

PMID- 20670645
TI  - Antibody and cell-mediated immune responses to Staphylococcus aureus small colony
      variants and their parental strains associated with bovine mastitis.
AB  - Persistence of bovine Staphylococcus aureus mastitis may be associated with the
      small colony variant (SCV) form that is adapted to intracellular life and resists
      elimination by the immune system. This study evaluated antibody-mediated (AMIR)
      and cell-mediated immune responses (CMIR) to two bovine SCV forms and their
      parent strains isolated from cows with mastitis. Four groups of healthy cows,
      five cows/treatment group, were challenged by the intramammary route with
      naturally occurring bovine SCV Heba3231, its parent strain 3231, a hemB mutant
      displaying the SCV phenotype or its parent strain, Newbould 305. Blood and milk
      samples were collected at day 0 before challenge and at days 1, 14, 21 and 36
      post-challenge to determine antigen-specific immunoglobulin (Ig) IgG(1) and
      IgG(2) antibody responses as indicators of type 2 and type 1 responses,
      respectively. At day 24 post-challenge cows in each group were inoculated with
      the UV-killed homologous strain intradermally in the neck to induce delayed-type
      hypersensitivity (DTH) as an indicator of CMIR. The SCV Heba3231 and 3231 strains
      induced significant IgG(1) and IgG(2) antibody responses in sera and in sera and
      milk whey, respectively. The hemB SCV mutant and Newbould 305 strains induced
      significant IgG(1) antibody in milk whey, and in sera and milk whey,
      respectively. The SCV Heba3231 and 3231 strains induced DTH, the hemB mutant
      induced intermediate hypersensitivity, and Newbould 305 failed to induce DTH.
      These results indicate marked differences in immune responses induced by parent
      and SCV forms of the same strain of S. aureus and by the two wild-type strains.
      This is the first study to evaluate both AMIR and CMIR in the context of
      persistent bovine mastitis to different and genetically characterized strains of
      S. aureus including two SCVs. The findings expand our understanding of immune
      responses to persistent S. aureus mastitis.

PMID- 20670646
TI  - Enhancement of axonal potassium conductance reduces nerve hyperexcitability in an
      in vitro model of oxaliplatin-induced acute neuropathy.
AB  - Oxaliplatin is used in the chemotherapeutic treatment of malignant tumours. A
      common side effect of oxaliplatin is an acute peripheral neuropathy characterized
      by axonal hyperexcitability, which can be painful and is aggravated by exposure
      to cold. Electrophysiological studies on isolated segments of peripheral rodent
      nerve have been able to replicate oxaliplatin's effect on axonal
      hyperexcitability in vitro. In the present study we have used this in vitro model
      to examine whether flupirtine, a clinically available analgesic, which activates
      slow axonal potassium (Kv7) channels, can suppress axonal hyperexcitability
      resulting from exposure of peripheral nerve to oxaliplatin. In the presence of
      oxaliplatin (30MUM), the A-fibre compound action potential response of isolated
      rat nerve segments to a brief electrical stimulus (0.1ms) changed considerably
      with the emergence of after-activity that persisted for a period of tens of
      milliseconds after the electrical stimulus. Lowering the bath temperature by 4
      degrees C enhanced the magnitude and prolonged the time course of this axonal
      after-activity. Application of flupirtine (10MUM) reduced both the magnitude and
      duration of oxaliplatin-induced axonal after-activity in myelinated axons. These
      findings were also confirmed in isolated human sural nerve segments. The data
      indicate that activation of slow potassium channels in the A-fibres of peripheral
      nerve may attenuate the acute neuropathy associated with oxaliplatin in humans.

PMID- 20670647
TI  - Emergence of tigecycline resistance amongst multi-drug resistant gram negative
      isolates in a multi-disciplinary hospital.

PMID- 20670648
TI  - Antituberculosis drug-induced liver injury in chronic hepatitis and cirrhosis.
AB  - OBJECTIVES: To evaluate the incidence, risk factors and outcomes for anti
      tuberculosis (TB) drug-induced liver injury (DILI) in patients with chronic liver
      disease including cirrhosis. METHODS: A total of 107 patients with chronic liver
      disease were assessed for anti-TB DILI. Anti-TB DILI was defined as elevation of
      alkaline phosphatase (ALP), aspartate transaminase, or alanine transaminase, or
      an increase in Child-Turcotte-Pugh score within 2 months of initiating anti-TB
      medication. The risk factors for anti-TB DILI were evaluated by multivariate
      logistic regression analysis. RESULTS: Fifty-eight (54%) patients had cirrhosis.
      Of 93 patients receiving one or more hepatotoxic anti-TB drugs, 18 (17%)
      experienced DILI: 11 (24%) among 46 patients with chronic hepatitis and 7 (15%)
      among 46 patients with compensated liver cirrhosis (P = 0.271). Independent risk
      factors for DILI were female sex, number of hepatotoxic anti-TB drugs
      administered and baseline ALP levels but not cirrhosis itself. Of the 18 patients
      with DILI, 13 (72%) successfully completed anti-TB treatment after switching to
      less hepatotoxic drug regimens. CONCLUSIONS: Hepatotoxic anti-TB drugs may be
      safely used in the patients with chronic liver disease including compensated
      cirrhosis if number of hepatotoxic drugs used is adjusted appropriately.

PMID- 20670649
TI  - Severe, critical and fatal cases of 2009 H1N1 influenza in China.
AB  - OBJECTIVE: For severe, critical and fatal cases of 2009 H1N1 influenza in the
      winter in the Northern Hemisphere, the detailed features are not fully known. The
      aim of this study was to examine these features through describing these cases in
      Beijing, China in 2009. METHODS: Data on severe, critical and fatal cases were
      collected via the Notifiable Disease Surveillance System and a designated
      surveillance system for managing 2009 H1N1 influenza cases in Beijing. The
      characteristics and risk factors of these cases were elucidated. RESULTS: A total
      of 475 severe cases, 73 critical ones and 69 deaths were identified in 2009. The
      proportion of obesity was low, as well as pregnancy. About half of them had no
      underlying disease. Most of deaths had multi-organ failure, with a median
      interval from illness onset to death of ten days. Delay in visiting hospital,
      cardiovascular disease and allergy predicted a higher risk of severe disease, and
      cases aged 6-17 years were at lower risk. Cases not promptly receiving
      neuraminidase inhibitors were at increased risk of death. CONCLUSIONS: Age and
      underlying disease are significantly associated with severity of outcomes of 2009
      H1N1 influenza; prompt presentation to hospital and use of neuraminidase
      inhibitor were protective.

PMID- 20670650
TI  - Household transmission of pandemic 2009 influenza A (H1N1) virus in Osaka, Japan
      in May 2009.
AB  - OBJECTIVE: To assess household transmission of pandemic influenza A (H1N1) and
      effectiveness of postexposure prophylaxis (PEP) of antiviral drugs among
      household contacts of patients during the first pandemic influenza A (H1N1)
      outbreak in Osaka, Japan in May 2009. METHODS: Active surveillance of patients
      and their families was conducted. Public Health Center staff visited each home
      with an infected patient and advised every household member with regard to
      precautionary measures, and PEP was provided to household contacts to prevent
      secondary infection. We analyzed the effectiveness of PEP and characteristics of
      secondary infection. RESULTS: The secondary attack rate (SAR) among household
      contacts was 3.7%. The SAR among household contacts without PEP was 26.1%.
      However, the SAR among those with PEP was 0.6%. Only two of 331 household
      contacts with PEP became infected. One of the two was infected with an
      oseltamivir-resistant strain. Analysis of SAR by age group showed that those
      under 20 years of age were at higher risk than those over 20 (relative risk [RR]
      = 7.9; 95% confidence interval [CI] = 2.24-27.8). Significant differences with
      respect to sex, number of household contacts, and use of antiviral medications in
      the index cases were not observed. CONCLUSIONS: Our present results indicate that
      PEP is effective for preventing secondary H1N1 infection among household
      contacts.

PMID- 20670651
TI  - Significance of high levels of procalcitonin in patients with influenza A (H1N1)
      pneumonia.

PMID- 20670652
TI  - Clinical impact of methicillin resistance on outcome of patients with
      Staphylococcus aureus infection: a stratified analysis according to underlying
      diseases and sites of infection in a large prospective cohort.
AB  - OBJECTIVE: This study was conducted to identify the predictors of mortality and
      to evaluate the impact of methicillin resistance on outcome in patients with
      Staphylococcus aureus infection according to underlying conditions and type of
      infection. METHODS: An observational cohort study including 4949 patients with S.
      aureus infection was conducted. We compared data from patients with MRSA
      infection with those with MSSA infection. RESULTS: The 30-day mortality rate of
      MRSA group was significantly higher than that of MSSA group (15.6% vs. 6.2%, P <
      0.001). However, MRSA infection was not found to be independent risk factor for
      mortality after adjusting for other variables (OR = 1.03, 95% CI = 0.80-1.32).
      When we analyzed patients with S. aureus bacteremia (n = 709), MRSA infection was
      found to be significantly associated with mortality in multivariate analysis
      (Adjusted OR = 1.69, 95% CI = 1.15-2.49). When the 30-day mortality rates were
      compared according to underlying diseases, the 30-day mortality rate of MRSA
      group was significantly higher than that of MSSA group in patients with
      malignancy or renal diseases. MRSA infection was also found to be one of the
      independent risk factors for mortality in patients with malignancy (adjusted OR =
      1.69, 95% CI = 1.06-2.70) and in those with renal disease (adjusted OR = 1.70,
      95% CI = 1.0-2.89), after adjustment for host variables. CONCLUSIONS: Methicillin
      resistance adversely affected the outcome of patients with S. aureus infection,
      in patients with cancer or renal disease and in those with S. aureus bacteremia,
      although MRSA infection was not found to be significantly associated with higher
      mortality in overall patient population.

PMID- 20670653
TI  - Non-magnetic equipment for the high-resolution quantification of finger
      kinematics during functional studies of bimanual coordination.
AB  - Simultaneous recording of behavioral and functional data is crucial in capturing
      the neural mechanisms underpinning human motor actions. We describe a non
      magnetic equipment (NME) to record finger kinematics, in particular the absolute
      amplitude of finger oscillation, during bimanual coordination paradigms performed
      in functional studies. NME monitors finger movements with optic fiber signals
      that are post-processed off-line to quantify finger kinematics. A phantom
      experiment demonstrated no mutual interference between NME and fMRI, hence the
      usability of NME in environments sensitive to electro-magnetic fields. The
      spatial and temporal resolutions of NME data (1 mm and 1 ms), its reliability and
      feasibility when studying human subjects were verified with two comparative
      experiments performed with NME and a validated infrared camera (IRC) system.
      Results showed that the restrictions of NME (reduction of degrees of freedom of
      the coordinated system and potential haptic feedback) do not interfere with the
      correct reconstruction of finger kinematics. We also demonstrated that the
      recorded behavioral information can be used to detect neural activity associated
      with specific features of coordinated behavior. Therefore, we believe that the
      use of NME for the combined analysis of behavioral and functional data may help
      assessing an adequate interpretation of the cortical activity associated with
      specific tasks. This approach might as well help to explore the role of specific
      brain areas in motor processes, with a potential great impact in the diagnosis
      and subsequent intervention in brain injured patients, or in children affected by
      developmental coordination disorders.

PMID- 20670654
TI  - Chemical neurostimulation using pulse code modulation (PCM) microfluidic chips.
AB  - We report the implementation of a chemical neurostimulation technique using
      microfluidic devices. The microfluidic chip in this research is used for the in
      vitro study of the nervous system of Aplysia californica under localized chemical
      stimulation. The polydimethylsiloxane (PDMS) device is a one-bit pulse code
      modulator that digitally controls the concentration of the non-hydrolysable
      cholinergic agonist carbachol injected directly above a ganglion. The chip was
      successful in repeatedly and controllably inducing bursts of ingestive-like
      patterns. The ability of the chip to induce rhythmic activity through the sheath
      of the ganglion suggests that it could serve as the basis for an implantable, in
      vivo device to control neural activity and motor behavior using chemical
      stimulation.

PMID- 20670655
TI  - The influence of IgG density and macrophage Fc (gamma) receptor cross-linking on
      phagocytosis and IL-10 production.
AB  - We have previously demonstrated that the addition of immune complexes (IC) to
      stimulated macrophages could profoundly influence cytokine production. In the
      present work we sought to determine the density of IgG on immune complexes
      necessary to mediate phagocytosis, inhibit IL-12 production and induce IL-10
      production from stimulated macrophages. We developed immune complexes with
      predictable average densities of surface-bound immunoglobulin. We show that a
      threshold amount of IgG was necessary to mediate attachment of IC to macrophages.
      At progressively higher densities of IgG, Fc receptor-mediated phagocytosis
      resulted in an inhibition of IL-12 production and then an induction of IL-10. The
      reciprocal alterations in these two cytokines occurred when as little as one
      optimally opsonized SRBC was bound per macrophage. Macrophage IL-10 induction by
      immune complexes was associated with the activation of the MAP kinase, ERK, which
      was progressively increased as a function of IgG density. We conclude that signal
      transduction through the macrophage Fcgamma receptors vary as a function of
      signal strength. At moderate IgG densities, especially in the presence of
      complement, efficient phagocytosis occurs in the absence of cytokine alterations.
      At slightly higher IgG densities IL-12 production is shut off and eventually IL
      10 induction occurs. Thus, the myriad events emanating from FcgammaR ligation
      depends on the density of immune complexes, allowing the Fc receptors to fine
      tune cellular responses depending on the extent of receptor cross-linking.

PMID- 20670656
TI  - Rapid sample preparation for detection and identification of avian influenza
      virus from chicken faecal samples using magnetic bead microsystem.
AB  - Avian influenza virus (AIV) is an infectious agent of birds and mammals. AIV is
      causing huge economic loss and can be a threat to human health. Reverse
      transcriptase polymerase chain reaction (RT-PCR) has been used as a method for
      the detection and identification of AIV virus. Although RT-PCR is a sensitive
      method for detection of AIV, it requires sample preparation including separation
      and purification of AIV and concentrate viral RNA. It is laborious and complex
      process especially for diagnosis using faecal sample. In this study, magnetic
      beads were used for immunoseparation of AIV in chicken faecal sample by a
      magnetic microsystem. Using this system, all the 16 hemagglutinin (H) and 9
      neuraminidase (N) subtypes of AIV were separated and detected in spiked faecal
      samples using RT-PCR, without an RNA extraction step. This rapid sample
      preparation method can be integrated with a total analysis microsystem and used
      for diagnosis of AIV.

PMID- 20670657
TI  - Development and application of a broadly reactive real-time reverse transcription
      PCR assay for detection of murine noroviruses.
AB  - Murine norovirus (MNV) is a viral agent newly identified in laboratory mice and a
      large number of genetically diverse MNV strains have been reported to date. A
      broadly reactive TaqMan-based real-time reverse transcription (RT)-polymerase
      chain reaction (PCR) assay was developed for MNVs. Novel primers and a TaqMan MGB
      probe were designed targeting highly conserved sequences among MNV strains, which
      are located in the open reading frames 1 (ORF1)-ORF2 junction region. The
      quantitative range of this assay was determined as 1.0 * 10(2)-1.0 *
      10(8)copies/PCR tube based on a 10-fold serial dilution of plasmid DNA containing
      the target sequences. Viral RNA in eight murine stool specimens positive by
      nested RT-PCR assay was measured, and the highest viral RNA load was calculated
      at 4.7 * 10(6)copies/g-stool. MNV was inoculated into RAW 264.7 cells, and the
      viral RNA was monitored to validate assay sensitivity. MNV-RNA in the supernatant
      was detected during in vitro replication, which increased substantially from 5 to
      30 h post-infection (hpi) and reached more than 1.0 * 10(10)copies/mL at 96 hpi.
      This real-time RT-PCR assay is a useful tool to detect and quantify MNV-RNA in in
      vivo and in vitro studies.

PMID- 20670658
TI  - Human papillomavirus detection and typing in thin prep cervical cytologic
      specimens comparing the Digene Hybrid Capture II Assay, the Roche Linear Array
      HPV Genotyping Assay, and the Kurabo GeneSquare Microarray Assay.
AB  - Three methods for the detection of HPV DNA were compared in cervical cytologic
      specimens: the Digene Hybrid Capture II Assay (HC), the Roche Linear Array HPV
      Genotyping Assay (LA) and the Kurabo GeneSquare Microarray (GS). The main goals
      of the study were to correlate cytology with HPV detection and to determine
      agreement between assay pairs for HPV detection. Thin-prep Pap smears were
      performed and supernates were tested by HC, LA, and GS. For specimens reacting
      with the HPV 52/33/35/58 probe in the LA assay, type-specific PCR was performed
      for HPV types 52, 33, 35, or 58. Binomial proportions and kappa coefficients were
      calculated for agreement between assays. Cytology results and supernatant were
      available for 202 subjects. HPV detection increased with worsening cytologic
      abnormality in all three assays. For all cytologic groups, LA and GS detected
      more HPV (all and oncogenic) than HC. However, for detection of oncogenic HPV
      types represented in all three assays, differences between assays were less
      pronounced. The highest agreement was between LA and GS. In four of 12 specimens
      reacting with the HPV 52/33/35/58 probe in the LA assay but deemed HPV 52-LA
      negative using an algorithm provided by the manufacturer, the presence of HPV 52
      was confirmed using type-specific HPV 52 PCR. All four of these specimens were
      also GS-positive for HPV 52.

PMID- 20670659
TI  - Cloning, characterisation and heterologous expression of an astacin
      metalloprotease, Sc-AST, from the entomoparasitic nematode Steinernema
      carpocapsae.
AB  - Steinernema carpocapsae is a parasitic nematode that is high virulent to insects.
      The parasitic juvenile reaches the insect haemocoelium by passing through mid-gut
      barriers and develops there. During invasion, the nematode was predicted to
      express a large set of proteases, including metalloproteases, one of which was
      sequenced and expressed in this work. A 1583-nucleotide cDNA encoding a putative
      metalloprotease containing a 28-aa signal peptide, a 79-aa propeptide and a 311
      aa mature protease with a predicted molecular mass of 35.2 kDa and a theoretical
      pI of 5.9 was cloned from the parasitic stage of the nematode. Sequence analyses
      predicted signature sequences of the astacin metalloprotease family, an astacin
      domain, a zinc-binding motif and a methionine turn motif; therefore, this protein
      was identified as an astacin and designated as Sc-AST. The astacin domain of Sc
      AST has an amino acid sequence homology of 46% to prototypical astacin from
      Astacus astacus and 82% to Caenorhabditis elegans NAS-8. Like NAS-8 of C.
      elegans, Sc-AST has a C-terminal ShK toxin domain. Recombinant Sc-AST was
      produced in an Escherichia coli system and was purified by affinity
      chromatography. Maldi-MS/MS analysis of purified recombinant protein matched the
      Sc-AST sequence with a significance score of 499. Sc-AST was produced in the
      correct folding conformation, showed activities against gelatin and azocasein
      substrates and was inhibited by divalent metal-chelating agents. Sc-AST presented
      an optimum pH of 7.5 and temperature of 37 degrees C and K(m), V(max) and k(cat)
      values of 1.86 mM, 0.281 MUM/min and 27.9 s(-1), respectively. Expression
      analyses indicated that Sc-AST is up-regulated in the parasitic stage and is
      strongly induced in vitro by insect tissues, thus suggesting that it plays a role
      in the parasitic process.

PMID- 20670660
TI  - Influence of transposition and insertion of additional binding domain on
      expression and characteristics of xylanase C of Clostridium thermocellum.
AB  - Clostridium thermocellum encodes a xylanase gene (xynC) which is the major
      component of its cellulosome. XynC is a multidomain enzyme comprising of a
      substrate binding domain at the N-terminal followed by the catalytic domain and a
      dockerin domain. To study the influence of binding domain on activity, stability
      and expression of the enzyme the protein with the binding domain at C-terminal
      (XynC-CB), and the one with the binding domain at both N- and C-terminal (XynC
      BCB) were expressed in E. coli. Recombinant plasmids, pXynC-CB and pXynC-BCB were
      constructed by inserting the corresponding gene in pET22b(+). XynC-CB and XynC
      BCB were expressed at levels around 30% and 33% of the total E. coli cell
      proteins, respectively, while losing 40% and 20% of their activities at 70
      degrees C for 120 min, respectively. The specific activities of XynC-CB, XynC-BCB
      were 76 and 98 U mg(-1), while the activities on equimolar basis were 4410 and
      7450 U MUM(-1) against birchwood xylan, respectively. Their overall activities
      produced in the culture were 3660 and 5430 U L(-1) OD(600)(-1). Substrate binding
      studies showed that in case of XynC-C 51% of the activity remained unbound to
      birchwood xylan, whereas in the cases of XynC-BC, XynC-CB and XynC-BCB the
      activities left unbound were 33%, 32% and 12%, respectively, under the assay
      conditions used. Similar binding values were obtained in the case of oat spelt
      xylan. K(m) values for XynC-CB and XynC-BCB against birchwood xylan were found to
      be 3.1 and 1.47 mg ml(-1), respectively. Thus addition of a second carbohydrate
      binding domain at the C-terminal of the catalytic domain enhances activity,
      substrate affinity as well as thermostability.

PMID- 20670661
TI  - Optimization of antibody fragment production in Bacillus megaterium: the role of
      metal ions on protein secretion.
AB  - The effect of the concentration of metal ions in minimal media has been shown to
      be very important for the production and secretion of the antibody fragment D1.3
      scFv in Bacillus megaterium YYBm1. The best media compositions for biomass and
      antibody fragment formation were evaluated using a genetic algorithm. The
      screening was carried out in 96 microtiter deep well plates with 900 MUL
      cultivation volume. In 7 generations, 240 different kinds of media were tested,
      key elements for production and secretion were detected and a 117% increase in
      production of antibody fragment compared to the previously used medium could be
      achieved. In addition, media with a higher biomass formation (+84%) or with both
      more biomass and a higher production of antibody fragment (Pareto-front members)
      were found. Interestingly the best media for protein production and secretion
      were different in their composition, with regards to the metal ion concentration
      levels. From data derived experimentally and from the genome, magnesium was shown
      to be one of the key components of the metal ions tested for biomass formation
      and especially for production and secretion of the antibody fragment D1.3 scFv.

PMID- 20670662
TI  - Structure monomorphism of RNA G-quadruplex that is independent of surrounding
      condition.
AB  - G-quadruplex structures in nucleic acids have become attractive targets of study
      because their distinct structural forms may have diverse biological functions.
      Here, we preliminary investigated the structure and thermodynamics of G
      quadruplexes of RNAs and corresponding DNAs of the same sequence by CD, UV and
      PAGE. Structural analysis demonstrated that the RNA sequences folded into a
      parallel-stranded G-quadruplex independently of surrounding conditions with
      different cations (K(+) and Na(+)) under both dilute and molecular crowding
      conditions. In contrast, G-quadruplexes of their corresponding DNA sequences
      showed structural polymorphism depending on the surrounding conditions. Moreover,
      it was demonstrated that parallel G-quadruplexes of the RNA sequences were more
      stable than either parallel or antiparallel G-quadruplexes of the same DNA
      sequences. These results allow us to propose a single, robust RNA G-quadruplex
      structure that exists under various conditions.

PMID- 20670663
TI  - Foaming of proteins: New prospects for enzyme purification processes.
AB  - Efficient techniques for the isolation of enzymes from a microbial production
      culture are required to meet the growing needs of the "White Biotechnologies" for
      novel catalysts. Traditional protein purification procedures typically comprise
      multistep operations, which inevitably come along with significant losses of
      enzyme activity. Foaming offers an alternative minimizing the processing steps,
      preserving the purification efficiency and decreasing the activity losses all at
      the same time. This review provides an insight into the foaming process itself
      and its application in separating enzymes from model systems and from complex
      media, such as microbial cultures. Examples demonstrate fractionated foaming and
      the tweezer technique.

PMID- 20670664
TI  - Enantioselective transesterification by Candida antarctica Lipase B immobilized
      on fumed silica.
AB  - Enzymatic catalysis to produce molecules such as perfumes, flavors, and
      fragrances has the advantage of allowing the products to be labeled "natural" for
      marketing in the U.S., in addition to the exquisite selectivity and
      stereoselectivity of enzymes that can be an advantage over chemical catalysis.
      Enzymatic catalysis in organic solvents is attractive if solubility issues of
      reactants or products, or thermodynamic issues (water as a product in
      esterification) complicate or prevent aqueous enzymatic catalysis. Immobilization
      of the enzyme on a solid support can address the generally poor solubility of
      enzymes in most solvents. We have recently reported on a novel immobilization
      method for Candida antarctica Lipase B on fumed silica to improve the enzymatic
      activity in hexane. This research is extended here to study the enantioselective
      transesterification of (RS)-1-phenylethanol with vinyl acetate. The maximum
      catalytic activity for this preparation exceeded the activity (on an equal enzyme
      amount basis) of the commercial Novozyme 435((r)) significantly. The steady-state
      conversion for (R)-1-phenylethanol was about 75% as confirmed via forward and
      reverse reaction. The catalytic activity steeply increases with increasing
      nominal surface coverage of the support until a maximum is reached at a nominal
      surface coverage of 230%. We hypothesize that the physical state of the enzyme
      molecules at a low surface coverage is dominated in this case by detrimental
      strong enzyme-substrate interactions. Enzyme-enzyme interactions may stabilize
      the active form of the enzyme as surface coverage increases while diffusion
      limitations reduce the apparent catalytic performance again at multi-layer
      coverage. The temperature-, solvent-, and long-term stability for CALB/fumed
      silica preparations showed that these preparations can tolerate temperatures up
      to 70 degrees C, continuous exposure to solvents, and long-term storage.

PMID- 20670665
TI  - Porcine reproductive and respiratory syndrome virus (PRRSV) in serum and oral
      fluid samples from individual boars: will oral fluid replace serum for PRRSV
      surveillance?
AB  - The purpose of this study was to determine whether oral fluid samples could be
      used to monitor individually-housed adult boars for porcine reproductive and
      respiratory syndrome virus (PRRSV) infection. In 3 trials, 24 boars were
      intramuscularly (IM) inoculated with a modified-live PRRSV (MLV) vaccine (Trial
      1), a Type 1 PRRSV isolate (Trial 2), or a Type 2 isolate (Trial 3). Oral fluid
      samples were collected daily and serum samples were collected twice weekly.
      Following the completion of the study, samples were randomized and blind-tested
      for PRRSV by real-time quantitative reverse-transcription polymerase chain
      reaction (qRT-PCR). PRRSV was detected in oral fluids at DPI 1 and all oral fluid
      specimens were PRRSV qRT-PCR positive at DPI 4. Although PRRSV was detected in
      both serum and oral fluid specimens through DPI 21, a comparison of matched
      samples from individual boars showed that oral fluid was equal to serum for the
      detection of PRRSV at DPI 7 and more likely to be positive than serum on DPI 14
      and 21. Overall, oral fluid was superior to serum for the detection of PRRSV
      using PCR over the 21-day observation period in this study. The results of this
      experiment suggest that individually-penned oral fluid sampling could be an
      efficient, cost-effective approach to PRRSV surveillance in boar studs and other
      swine populations.

PMID- 20670666
TI  - Carbohydrate and fat digestion is necessary for maximal suppression of total
      plasma ghrelin in healthy adults.
AB  - It is uncertain whether the postprandial suppression of ghrelin is dependent on
      digestion and absorption of nutrients or whether the presence of nutrients in the
      small intestine is sufficient. Twenty-four healthy young adults with a mean age
      of 23 +/- 0.6 years were examined on 3 separate days after an overnight fast.
      Twelve subjects participated in Part A, and the other 12 subjects in Part B. In
      Part A, subjects consumed, in random order, one of three study drinks: 300 mL
      water; 300 mL high-fat drink, with and without, 120 mg orlistat. In Part B,
      subjects received, in random order, one of three drinks: 300 mL water; 300 mL
      sucrose, with and without, 100mg acarbose. In both parts gastric emptying as
      measured by 2-D ultrasound. In Part A, plasma ghrelin concentrations decreased
      following ingestion of the high-fat drink, but did not change with the high-fat
      orlistat drink or water. In Part B, the suppression of plasma ghrelin following
      the sucrose drink, was attenuated by acarbose. Orlistat accelerated gastric
      emptying of the high-fat drink, while acarbose delayed gastric emptying of the
      sucrose drink. In conclusion, fat and carbohydrate digestion is required for
      maximal suppression of ghrelin secretion.

PMID- 20670667
TI  - Prostate cancer, masculinity and food. Rationales for perceived diet change.
AB  - Research indicating that certain diets can lower prostate-specific antigen levels
      suggests that diet change might be a beneficial treatment adjunct for low-grade
      prostate cancer. However, few men with prostate cancer adopt significant diet
      change, indicating a need to better understand how and why they make food
      choices. This qualitative study explored men's perceptions of their diets
      following a prostate cancer diagnosis, and the rationales underpinning diet
      changes (or lack thereof). Individual semi-structured interviews were conducted
      with 14 men ages 48-78 years who had been diagnosed with prostate cancer within
      the previous 5 years. Findings show that participants exhibited varied dietary
      patterns, which we labeled 'eating as usual', 'intensifying efforts', 'adding
      on', and 'overhauling diets'. Four main domains informed rationales for diet
      changes or lack thereof: perception of pre-prostate cancer diet, diet and health
      understandings, orientation towards prostate cancer, and the need for "doing
      something." Dietary ideals framed as masculine, important, action-oriented and
      autonomous endeavors contributed to participants' food choice behaviors,
      suggesting that their alignment to masculine dietary ideals influenced if and how
      they engaged in diet change. A better understanding of how masculine food ideals
      shape food choice might be useful in expanding food choice models and in
      developing effective nutrition education interventions for this group.

PMID- 20670669
TI  - Chemical composition, antimicrobial and antioxidant activities of the essential
      oils of Sideritis erythrantha Boiss. and Heldr. (var. erythrantha and var.
      cedretorum P.H. Davis) endemic in Turkey.
AB  - In the present study, chemical compositions, antimicrobial and antioxidant
      activities of the essential oils of Sideritis erythrantha var. erythrantha (SE)
      and Sideritis erythrantha var. cedretorum (SC), which are endemic taxa in Turkey,
      were investigated. The essential oils obtained by hydrodistillation were analyzed
      by gas chromatography-mass spectrometry (GC-MS). alpha-Pinene was the major
      component of the essential oils of SC and SE. SC essential oil was as effective
      as antibiotic against methicillin-resistant Staphylococcus aureus (MRSA),
      vancomycin resistant Enterococcus faecalis (VRE), ampicillin resistant
      Haemophilusinfluenzae and vancomycin sensitive E. faecalis. Similarly, SE
      essential oil was also as effective as antibiotic against VRE and ampicillin
      resistant H. influenzae. Antioxidant activities of the essential oils of SC and
      SE were determined by 1,1-diphenyl-2-picrylhydrazyl (DPPH), beta
      carotene/linoleic acid and reducing power. Both essential oils exhibited weak
      antioxidant activity. This is the first report on antimicrobial and antioxidant
      activities of the essential oils of SC and SE.

PMID- 20670670
TI  - Color difference thresholds in dental ceramics.
AB  - OBJECTIVES: The objective of the study was to determine the perceptibility and
      acceptability thresholds for dental ceramics using CIEDE2000 (DeltaE(00)) and
      CIELAB (DeltaE(ab)(*)) color difference formulas and a novel TSK Fuzzy
      Approximation. METHODS: A 13-observer panel performed independent observations of
      perceptibility and acceptability judgments on 105 pairs of ceramic discs (14mm in
      diameter and 3mm thick). Color differences of the disc pairs were calculated
      using both color difference formulas (DeltaE(00) ranged from 0.10 to 9.91). Two
      fitting procedures were used: S-shaped curve and TSK Fuzzy Approximation. For
      both procedures, from the resultant fitting curves, the 95% confidence intervals
      were estimated and the 50:50% thresholds were calculated (50% positive and 50%
      negative answers). RESULTS: With the S-shaped fitting procedure, a 50:50%
      acceptability threshold was found to be DeltaE(00)=2.25 (r(2)=0.88) and
      DeltaE(ab)(*)=3.46 (r(2)=0.85). Corresponding values with a TSK Fuzzy
      Approximation were DeltaE(00)=2.23 (r(2)=0.89) and DeltaE(ab)(*)=3.48
      (r(2)=0.86). The perceptibility thresholds for fitted S-shape curves were
      DeltaE(00)=1.30 (r(2)=0.74) and DeltaE(ab)(*)=1.80 (r(2)=0.70) and
      DeltaE(00)=1.25 (r(2)=0.75), and DeltaE(ab)(*)=1.74 (r(2)=0.71) for the TSK Fuzzy
      Approximation. The DeltaL', DeltaC', DeltaH' values corresponding to a 50%
      acceptability threshold were DeltaL'=2.44, DeltaC'=3.15 and DeltaH'=3.24
      respectively. CONCLUSIONS: The CIEDE2000 color difference formula provided a
      better fit than CIELAB formula in the evaluation of color difference thresholds
      of dental ceramics. There was a statistically significant difference between
      perceptibility and acceptability thresholds for dental ceramics. The TSK Fuzzy
      Approximation has been proved to be a reliable alternative approach for the color
      threshold calculation procedure.

PMID- 20670671
TI  - Resistance of T-cell acute lymphoblastic leukemia to tumor necrosis factor-
      related apoptosis-inducing ligand-mediated apoptosis.
AB  - OBJECTIVE: Cytotoxic ligands are involved in tumor immunity and graft-vs.
      leukemia effect after allogeneic stem cell transplantation for leukemia. To
      clarify the susceptibility of T-cell acute lymphoblastic leukemia (T-ALL) to
      tumor immunity, sensitivity to recombinant human soluble Fas ligand (rhsFasL) and
      tumor necrosis factor-related apoptosis-inducing ligand (rhsTRAIL) was
      determined. MATERIALS AND METHODS: Sensitivity to rhsFasL and rhsTRAIL and cell
      surface expression of their receptors were tested in T-ALL cell lines (n = 7) and
      patients' samples (n = 17) and compared with those in B-precursor ALL cell lines
      (n = 30). Expression of components of the death-inducing signaling complex and
      the TRAIL receptor genes (DR4/DR5), and the methylation status and promoter
      activity of the DR4/DR5 gene were tested in T-ALL cell lines. RESULTS: T-ALL cell
      lines showed higher level of Fas expression and higher sensitivity to rhsFasL
      than did B-precursor ALL cell lines. Despite comparable expression of components
      of death-inducing signaling complex, cell lines and patients' samples of T-ALL
      showed TRAIL-resistance associated with low cell surface expression of DR4/DR5.
      Gene expression of DR4/DR5 in T-ALL cell lines was significantly lower than that
      in B-precursor ALL cell lines, and the methylation status of the gene promoter in
      T-ALL cell lines was associated with the gene expression level at least for DR4.
      The demethylating agent, 5-aza 2'deoxycytidine, upregulated the gene expression
      of DR4/DR5, but was insufficient for their surface expression due to low basal
      promoter activity. CONCLUSIONS: In contrast to higher sensitivity to FasL, T-ALL
      showed resistance to TRAIL, which might be responsible for resistance to TRAIL
      mediated cellular immunity.

PMID- 20670672
TI  - Evaluation of a novel photoactive and biotinylated dehydroepiandrosterone analog.
AB  - To characterize the cell surface receptor for dehydroepiandrosterone (DHEA), we
      synthesized a DHEA analog containing biotin and benzophenone groups (DHEA-BP-Bt).
      DHEA-BP-Bt was equipotent with DHEA in competing with [(3)H]DHEA for binding to
      solubilized plasma membranes of bovine aortic endothelial cells (BAEC).
      Additionally, DHEA-BP-Bt pre-conjugated to avidin and immobilized on agarose,
      also inhibited plasma membrane binding of [(3)H]DHEA. Furthermore, DHEA-BP-Bt
      activated endothelial nitric oxide synthase, similar to DHEA. Confocal
      micrographs showed that, upon photoirradiation, DHEA-BP-Bt bound to sites on the
      cell surface of BAEC in a DHEA inhibitable manner. Finally, DHEA-BP-Bt bound
      specifically to proteins of approximately 55 kDa and 80 kDa, either when live
      cells were UV irradiated with the analog and plasma membrane proteins separated
      by SDS-PAGE or in a ligand blot analysis. These data confirm the successful
      synthesis of a photoactive, biotinylated DHEA analog which is capable of cross
      linking to and identifying plasma membrane DHEA binding sites and which will
      allow us to further purify this receptor.

PMID- 20670673
TI  - Is KIF24 a genetic risk factor for Frontotemporal Lobar Degeneration?
AB  - Linkage analysis identified a region on chromosome 9p associated with
      Frontotemporal Lobar Degeneration (FTLD). A detailed analysis of candidate genes
      lying in this region demonstrated an association with Ubiquitin Associated
      Protein (UBAP)1. The distribution of five Single Nucleotide Polymorphisms (SNPs)
      located in the chromosome 9 haplotype identified via linkage analysis, including
      UBAP1 rs7018487, UBAP2 rs1785506 and rs307658, and KIF24 rs17350674 and
      rs10814083, has been determined in a population of 284 patients diagnosed with
      FTLD, including 245 with behavioural variant Frontotemporal Dementia (bvFTD), 23
      with Progressive Aphasia and 16 with Semantic Dementia, compared with 318 age
      matched controls. A statistically significant increased frequency of the KIF24
      rs17350674 AA genotype was observed in patients compared with controls (7.4
      versus 2.5%; P=0.0068, OR: 3.63, CI: 1.58-8.35). Considering each syndrome
      separately, similar results where obtained in bvFTD versus controls (7.7 versus
      2.5%, P=0.005, OR: 3.26, CI: 1.40-7.57). Stratifying for gender, a statistically
      significant increased genotypic frequency was observed in female patients as
      compared with female controls (8.9 versus 2.5%, P=0.008, OR: 3.85, CI: 1.36
      10.93). In silico analysis predicted that the substitution from W to L caused by
      the rs17350674 affects protein function (P<0.05). The KIF24 rs17350674
      polymorphism likely acts as a risk factor for sporadic FTLD, but a replication
      study would be needed to confirm these preliminary findings.

PMID- 20670674
TI  - A high-fat diet impairs neurogenesis: involvement of lipid peroxidation and brain
      derived neurotrophic factor.
AB  - Obesity is a growing global health problem that contributes to diabetes,
      hypertension, cardiovascular diseases, dementia, and cancer. The increased
      consumption of saturated fats in a high-fat diet (HFD) contributes to obesity,
      neurodegenerative diseases, long-term memory loss, and cognitive impairment. We
      tested whether HFD influences adult hippocampal neurogenesis. Male C57BL/6 mice
      were divided into two groups and maintained on either a normal diet (ND) or HFD.
      Seven weeks of HFD significantly decreased the numbers of newly generated cells
      in the dentate gyrus of the hippocampus without neuronal loss. HFD also increased
      the level of malondialdehyde (MDA) and decreased the level of brain-derived
      neurotrophic factor (BDNF) in the hippocampus. The toxic effects of MDA were
      evaluated on neural progenitor cells (NPCs). MDA reduced the growth of NPCs, but
      BDNF treatment restored NPCs proliferation. The present data indicate that a HFD
      impairs hippocampal neurogenesis and NPCs proliferation through increased lipid
      peroxidation and decreased BDNF.

PMID- 20670675
TI  - Mechanisms of L-DOPA-induced cytotoxicity in rat adrenal pheochromocytoma cells:
      implication of oxidative stress-related kinases and cyclic AMP.
AB  - L-DOPA therapy for Parkinson's disease has a double-edge effect on nigrostriatal
      dopaminergic neurons: L-DOPA increases the intracellular level of dopamine, but
      it induces neuron cytotoxicity in a concentration-dependent manner. To
      investigate the molecular signaling mechanisms that underlie the concentration
      dependent effects of L-DOPA on cell viability, the activities of mitogen
      activated protein kinases (MAPKs) and apoptotic enzymes were measured in rat
      adrenal pheochromocytoma (PC12) cells in the presence of a low concentration (20
      muM) and high concentrations (100-200 muM) of L-DOPA. At the low concentration, L
      DOPA was not cytotoxic and its presence increased the activities of extracellular
      signal-regulated kinase (ERK)1/2, p38 MAPK, BadSer112, Bcl-2, and caspase-12. At
      the high concentrations, L-DOPA was cytotoxic and stimulated the activities of
      ERK1/2, p38 MAPK, c-Jun N-terminal kinase (JNK)1/2, BadSer155, caspase-12 and
      caspase-3. The increased levels of ERK1/2 and BadSer155 in the presence of high
      concentrations of L-DOPA did not protect against L-DOPA-mediated cytotoxicity. In
      addition, the levels of L-type Ca(2+) channel-sensitive intracellular cyclic AMP
      (cAMP) and Ca(2+) were elevated in the presence of L-DOPA, and the increase in
      the levels of intracellular cAMP may also play a role in cellular viability,
      since cAMP levels and cytotoxicity increased in parallel with L-DOPA
      concentrations and the addition of forskolin in the medium increased cytotoxicity
      in a concentration-dependent manner. These results suggest that, at a low and non
      toxic concentration, L-DOPA may promote cell survival by increasing the
      activities of ERK1/2, BadSer112 and Bcl-2, while, at high concentrations, L-DOPA
      activates the caspase-3 cell death enzyme through the JNK1/2 and p38 MAPK
      signaling pathways as well as endoplasmic reticulum stress that activates caspase
      12. Intracellular cAMP levels may also play a role here. The results may lead to
      an effective therapy for Parkinson's disease.

PMID- 20670677
TI  - Cardiovascular reactivity and neuronal activation to stress in Schlager
      genetically hypertensive mice.
AB  - Schlager inbred hypertensive mice (BPH/2J) have been suggested to have high blood
      pressure (BP) due to an overactive sympathetic nervous system (SNS). The brain
      nuclei associated with the hypertension are also those involved in the
      integration of the cardiovascular responses to stress. Therefore, in the present
      study, we hypothesize that BPH/2J mice likely have a greater response to stress
      that is associated with greater neuronal activation in the limbic system,
      hypothalamus and medulla in regions known to regulate sympathetic activity. Male
      hypertensive BPH/2J and normotensive BPN/3J mice were implanted with telemetry
      devices and exposed to dirty cage-switch, an acute model of aversive stress.
      Stress exposure caused a 60% greater pressor response in BPH/2J compared with
      BPN/3J mice and an increase in activity, by contrast the level of tachycardia was
      less in BPH/2J mice. Stress-induced cardiovascular responses were also associated
      with greater neuronal activation, as detected by c-Fos expression, in BPH/2J
      compared with BPN/3J mice in the medial nucleus of the amygdala (MeAm),
      dorsomedial hypothalamus (DMH) (P<0.001) and marginally in the rostral
      ventrolateral medulla (RVLM; P=0.7). These findings suggest that hypertension in
      the BPH/2J mice is associated with greater sympathetic vasomotor responses to
      central pathways mediating the arousal responses to acute aversive stress in
      particular the amygdala, hypothalamus and rostral ventrolateral medulla.

PMID- 20670676
TI  - Neurosteroid withdrawal regulates GABA-A receptor alpha4-subunit expression and
      seizure susceptibility by activation of progesterone receptor-independent early
      growth response factor-3 pathway.
AB  - Neurosteroids regulate GABA-A receptor plasticity. Neurosteroid withdrawal occurs
      during menstruation and is associated with a marked increase in expression of
      GABA-A receptor alpha4-subunit, a key subunit linked to enhanced neuronal
      excitability, seizure susceptibility and benzodiazepine resistance. However, the
      molecular mechanisms underlying the upregulation of alpha4-subunit expression
      remain unclear. Here we utilized the progesterone receptor (PR) knockout mouse to
      investigate molecular pathways of PR and the transcription factor early growth
      response factor-3 (Egr3) in regulation of the GABA-A receptor alpha4-subunit
      expression in the hippocampus in a mouse neurosteroid withdrawal paradigm.
      Neurosteroid withdrawal induced a threefold increase in alpha4-subunit expression
      in wild-type mice, but this upregulation was unchanged in PR knockout mice. The
      expression of Egr3, which controls alpha4-subunit transcription, was increased
      significantly following neurosteroid withdrawal in wild-type and PR knockout
      mice. Neurosteroid withdrawal-induced alpha4-subunit upregulation was completely
      suppressed by antisense Egr3 inhibition. In the hippocampus kindling model of
      epilepsy, there was heightened seizure activity, significant reduction in the
      antiseizure sensitivity of diazepam (a benzodiazepine insensitive at
      alpha4betagamma-receptors) and conferral of increased seizure protection of
      flumazenil (a low-affinity agonist at alpha4betagamma-receptors) in neurosteroid
      withdrawn wild-type and PR knockout mice. These observations are consistent with
      enhanced alpha4-containing receptor abundance in vivo. Neurosteroid withdrawal
      induced seizure exacerbation, diazepam insensitivity, and flumazenil efficacy in
      the kindling model were reversed by inhibition of Egr3. These results indicate
      that neurosteroid withdrawal-induced upregulation of GABA-A receptor alpha4
      subunit expression is mediated by the Egr3 via a PR-independent signaling
      pathway. These findings help advance our understanding of the molecular basis of
      catamenial epilepsy, a neuroendocrine condition that occurs around the
      perimenstrual period and is characterized by neurosteroid withdrawal-linked
      seizure exacerbations in women with epilepsy.

PMID- 20670678
TI  - Nanostructure-initiator mass spectrometry (NIMS) imaging of brain cholesterol
      metabolites in Smith-Lemli-Opitz syndrome.
AB  - Cholesterol is an essential component of cellular membranes that is required for
      normal lipid organization and cell signaling. While the mechanisms associated
      with maintaining cholesterol homeostasis in the plasma and peripheral tissues
      have been well studied, the role and regulation of cholesterol biosynthesis in
      normal brain function and development have proven much more challenging to
      investigate. Smith-Lemli-Opitz syndrome (SLOS) is a disorder of cholesterol
      synthesis characterized by mutations of 7-dehydrocholesterol reductase (DHCR7)
      that impair the reduction of 7-dehydrocholesterol (7DHC) to cholesterol and lead
      to neurocognitive deficits, including cerebellar hypoplasia and austism
      behaviors. Here we have used a novel mass spectrometry-based imaging technique
      called cation-enhanced nanostructure-initiator mass spectrometry (NIMS) for the
      in situ detection of intact cholesterol molecules from biological tissues. We
      provide the first images of brain sterol localization in a mouse model for SLOS
      (Dhcr7(-/-)). In SLOS mice, there is a striking localization of both 7DHC and
      residual cholesterol in the abnormally developing cerebellum and brainstem. In
      contrast, the distribution of cholesterol in 1-day old healthy pups was diffuse
      throughout the cerebrum and comparable to that of adult mice. This study
      represents the first application of NIMS to localize perturbations in metabolism
      within pathological tissues and demonstrates that abnormal cholesterol
      biosynthesis may be particularly important for the development of these brain
      regions.

PMID- 20670679
TI  - Benzophenone-3 entrapped in solid lipid microspheres: formulation and in vitro
      skin evaluation.
AB  - Solid lipid microspheres (SLM), lipid-in-water formulations made from oil-and-wax
      mixtures, were studied concerning feasibility. SLMs were then loaded with a
      benzophenone-3, water insoluble UVAB-filter intended for dermal application.
      Microspheres were prepared by dispersion with homogenisers and investigated by
      polarizing micrography and scanning electron micrography. For the selected
      formulations, investigations on percutaneous penetration of B-3 capacity were
      performed "in vitro" using Franz cells. Microspheres, 5-50 MUm in size, and a
      spherical shape were obtained from several mixtures. B-3 was added and the
      loading capacity of this drug in the SLM was obtained for a maximum of 5% when
      the lipophilic phase was 18%. The lipophilic mixture with non-ionic surfactants
      in the selected formulation of lipid microspheres has a favorable effect on size.
      The selected formulation is also cosmetically adapted and it is composed of
      physiological and biodegradable lipids. B-3 was released and penetrated into skin
      more quickly and in greater quantity than in SLM form, from vehicles containing
      free B-3. This work has shown that SLM is an excellent carrier for lipophilic
      sunscreens like B-3 in order to decrease the release and penetration rate of this
      UV absorber compared with B-3 in oily solution.

PMID- 20670680
TI  - Translation of novel anti-cancer cytotoxicity biomarkers detected with high
      content analysis from an in vitro predictive model to an in vivo cell model.
AB  - Using high content analysis (HCA), we assessed whether cytotoxicity biomarkers
      translate from in vitro to in vivo models using four anti-cancer drugs
      (arabinoside C, arsenic trioxide, doxorubicin, and mitoxantrone) and staining
      live cells with Hoechst 33342 for DNA (nuclear area, nuclear intensity and cell
      number), Fluo-4 for ionised calcium, TMRM for mitochondrial membrane potential
      and TOTO-3 for plasma membrane permeability. Human HepG2 hepatocytes and Jurkat T
      lymphocytes were treated with 10-fold increasing concentrations of drug for 24
      and 72 h. We demonstrate that HCA can be carried out on suspension cells and that
      this in vivo model was at least as sensitive as the in vitro model. In addition,
      we show that the concentration of DOX in the nucleus and its anti-cancer
      mechanism of action can be assessed due to its intrinsic fluorescence and its DNA
      intercalation in competition with the Hoechst dye. We conclude cytotoxicity
      biomarkers translate from the in vitro, predictive, hepatocyte model to the in
      vivo lymphocyte model. Thus, HCA cytotoxicity biomarkers may not only be
      predictive of human toxicity potential but may be translatable for detection and
      monitoring of subclinical toxicity.

PMID- 20670681
TI  - Epstein-Barr virus latent membrane protein 1 increases chemo-resistance of cancer
      cells via cytoplasmic sequestration of Pim-1.
AB  - Improved treatment of EBV positive lymphoma depends on the identification of
      molecular mechanism underlying chemo-resistance. LMP1 is an essential
      transmembrane protein for EBV-induced immortalization of hematopoietic cells.
      Herein, we show that an oncogenic Pim-1 is translocated to the cytoplasm by LMP1.
      Three lines of evidence indicate that cytoplasmic sequestration of Pim-1 may be
      required for LMP1-induced cancer cell survival. First, Pim-1 enhanced the
      survival of LMP1-overexpressing cells treated with doxorubicin. Second, nuclear
      export of Pim-1 was sufficient to increase the survival. Third, knockdown of Pim
      1 effectively suppressed LMP-1-induced survival of cancer cells. Collectively,
      these data suggest that Pim-1 is a downstream target of LMP1, and that it
      contributes to the chemo-resistance of cancer cells.

PMID- 20670682
TI  - Zebrafish type XVII collagen: gene structures, expression profiles, and
      morpholino "knock-down" phenotypes.
AB  - The human COL17A1 gene encodes type XVII collagen (also known as the 180-kDa
      bullous pemphigoid antigen), an integral component of hemidesmosomes, attachment
      complexes providing integrity to the dermal-epidermal junction. Zebrafish, a
      useful model system to study skin development, displays fully developed
      hemidesmosomes at approximately 5 days post-fertilization (dpf). We have
      identified two COL17A1 orthologues in the zebrafish genome, col17a1a and
      col17a1b, which are expressed in the skin and the neural system, respectively.
      The proteins coded by these genes have structural module organizations homologous
      to the human type XVII collagen. "Knock-down" of the expression of col17a1a with
      a specific morpholino targeting the 5' UTR of the gene resulted in a blistering
      phenotype and in perturbations in the basement membrane zone. "Knock-down" of
      col17a1b expression resulted in ablation or in marked reduction of neuromasts in
      the lateral line. Thus, zebrafish has two COL17A1 orthologues which may have
      evolved tissue-specific functions during vertebrate development. Collectively,
      zebrafish provides a model system to study the molecular aspects of skin
      development and offers insights into the corresponding human diseases.

PMID- 20670683
TI  - The nitric oxide-donating pravastatin, NCX 6550, inhibits cytokine release and NF
      kappaB activation while enhancing PPARgamma expression in human
      monocyte/macrophages.
AB  - Previous studies have shown that NCX 6550 (NCX), a nitric oxide (NO)-donating
      pravastatin, induces anti-inflammatory effects in murine macrophage cell lines.
      Here, we have studied its activity in human monocyte/macrophages, by
      investigating cytokine release, NF-kappaB translocation and peroxisome
      proliferator-activated receptor gamma (PPARgamma) expression and function. For
      comparison, pravastatin, isosorbide-5-mononitrate (ISMN), sodium nitroprusside
      (SNP) and the PPARgamma ligand 15-deoxy-Delta(12,14)-prostaglandin J(2) (PGJ)
      were also tested. Monocytes and macrophages (MDM: monocyte-derived macrophages)
      were isolated from healthy donors; cytokine release was measured by ELISA, NF
      kappaB by electrophoretic mobility shift assay and PPARgamma by Western blot and
      Real-Time PCR. NCX (1 nM-50 MUM) dose-dependently inhibited phorbol 12-myristate
      13-acetate (PMA)-induced TNF-alpha release from monocytes (IC(50)=240 nM) and MDM
      (IC(50)=52 nM). At 50 MUM, it was more effective than pravastatin, ISMN and SNP
      (P<0.05), but less efficient than PGJ. Similar results were obtained for IL-6.
      Likewise, NCX was more effective than pravastatin and the other NO donors in
      inhibiting PMA-induced NF-kappaB translocation in both cell types, and, at the
      highest concentration, significantly (P<0.05) enhanced PPARgamma protein
      expression in monocytes. We conclude that NCX 6550 exerts a significant anti
      inflammatory activity in human monocyte/macrophages, that is also contributed by
      its NO donating properties, as the effects exerted by NCX are significantly
      higher than those evoked by pravastatin in many experimental assays. These data
      further indicate that the incorporation of a NO-donating moiety into a statin
      structure confers pharmacological properties which may translate into useful
      therapeutic benefits.

PMID- 20670684
TI  - Spatial HARDI: improved visualization of complex white matter architecture with
      Bayesian spatial regularization.
AB  - Imaging of water diffusion using magnetic resonance imaging has become an
      important noninvasive method for probing the white matter connectivity of the
      human brain for scientific and clinical studies. Current methods, such as
      diffusion tensor imaging (DTI), high angular resolution diffusion imaging (HARDI)
      such as q-ball imaging, and diffusion spectrum imaging (DSI), are limited by low
      spatial resolution, long scan times, and low signal-to-noise ratio (SNR). These
      methods fundamentally perform reconstruction on a voxel-by-voxel level,
      effectively discarding the natural coherence of the data at different points in
      space. This paper attempts to overcome these tradeoffs by using spatial
      information to constrain the reconstruction from raw diffusion MRI data, and
      thereby improve angular resolution and noise tolerance. Spatial constraints are
      specified in terms of a prior probability distribution, which is then
      incorporated in a Bayesian reconstruction formulation. By taking the log of the
      resulting posterior distribution, optimal Bayesian reconstruction is reduced to a
      cost minimization problem. The minimization is solved using a new iterative
      algorithm based on successive least squares quadratic descent. Simulation studies
      and in vivo results are presented which indicate significant gains in terms of
      higher angular resolution of diffusion orientation distribution functions, better
      separation of crossing fibers, and improved reconstruction SNR over the same
      HARDI method, spherical harmonic q-ball imaging, without spatial regularization.
      Preliminary data also indicate that the proposed method might be better at
      maintaining accurate ODFs for smaller numbers of diffusion-weighted acquisition
      directions (hence faster scans) compared to conventional methods. Possible
      impacts of this work include improved evaluation of white matter microstructural
      integrity in regions of crossing fibers and higher spatial and angular resolution
      for more accurate tractography.

PMID- 20670685
TI  - Cognitive training during infancy and adolescence accelerates adult associative
      learning: critical impact of age, stimulus contingency and training intensity.
AB  - A growing body of evidence supports the hypothesis that juvenile cognitive
      training shapes neural networks and behavior, and thereby determines the adult's
      capacity for learning and memory. In particular, we have shown that infant rats,
      even though they do not develop an active avoidance strategy in a two-way active
      avoidance task, show as adults accelerated learning in the same learning task.
      This indicates that a memory trace was formed in the infant rats, which most
      likely is recruited during adult training. To identify the learning conditions,
      which are essential prerequisites to form this memory trace in infancy or
      adolescence, we investigated the critical impact of: (i) age, (ii) CS-UCS
      contingency, and (iii) pre-training intensity on this facilitating effect. We
      observed: (i) an age-dependent improvement of avoidance learning, (ii) that the
      beneficial impact of infant or adolescent pre-training on adult learning
      increases with the age at pre-training, (iii) that CS-UCS contingency during
      infant pre-training was most efficient to accelerate adult learning, (iv) that
      pre-training intensity (i.e. number of pre-training trials) was positively
      correlated with the pre-training induced acceleration of adult learning, and (v)
      that infant rats, compared to adolescent rats, need a higher training intensity
      to show learning improvement as adults. These results indicate that infant rats
      develop a goal-oriented escape strategy, which during adult training is replaced
      by an avoidance strategy, facilitated by the recruitment of the CS-UCS
      association, which has been learned during infant training. Based on these
      results the future challenge will be to identify the specific contribution of
      prefronto-limbic circuits in infant and adult learning in relation to their
      functional maturation.

PMID- 20670686
TI  - In vitro screening of probiotic lactic acid bacteria and prebiotic
      glucooligosaccharides to select effective synbiotics.
AB  - Probiotics and prebiotics have been demonstrated to positively modulate the
      intestinal microflora and could promote host health. Although some studies have
      been performed on combinations of probiotics and prebiotics, constituting
      synbiotics, results on the synergistic effects tend to be discordant in the
      published works. The first aim of our study was to screen some lactic acid
      bacteria on the basis of probiotic characteristics (resistance to intestinal
      conditions, inhibition of pathogenic strains). Bifidobacterium was the most
      resistant genus whereas Lactobacillus farciminis was strongly inhibited. The
      inhibitory effect on pathogen growth was strain dependent but lactobacilli were
      the most effective, especially L. farciminis. The second aim of the work was to
      select glucooligosaccharides for their ability to support the growth of the
      probiotics tested. We demonstrated the selective fermentability of oligodextran
      and oligoalternan by probiotic bacteria, especially the bifidobacteria, for
      shorter degrees of polymerisation and absence of metabolism by pathogenic
      bacteria. Thus, the observed characteristics confer potential prebiotic
      properties on these glucooligosaccharides, to be further confirmed in vivo, and
      suggest some possible applications in synbiotic combinations with the selected
      probiotics. Furthermore, the distinctive patterns of the different genera suggest
      a combination of lactobacilli and bifidobacteria with complementary probiotic
      effects in addition to the prebiotic ones. These associations should be further
      evaluated for their synbiotic effects through in vitro and in vivo models.

PMID- 20670687
TI  - Trends in antibiotic resistance in Prevotella species from patients of the
      University Hospital of Maxillofacial Surgery, Sofia, Bulgaria, in 2003-2009.
AB  - Head-and-neck infections often involve anaerobes such as Prevotella species. Aim
      of the present study was to assess the evolution and the factors associated with
      resistance in Prevotella species to penicillin, clindamycin, metronidazole,
      tetracycline and beta-lactams/beta-lactamase inhibitors (BL/BLIs). In total, 192
      Prevotella strains, isolated from patients with oral and head-and-neck
      infections, were evaluated. Common isolates were Prevotella intermedia and
      Prevotella melaninogenica within the pigmented species as well as Prevotella oris
      and Prevotella oralis group within the non-pigmented species. Overall resistance
      was 43.2% for penicillin, 10.9% for clindamycin, 0% for metronidazole.
      Nonsusceptibility to tetracycline was 29.1% without significant differences in
      resistance rates between pigmented and other species. Penicillin resistant
      strains were beta-lactamase positive. From 2003-2004 to 2007-2009, penicillin
      resistance rates increased about four-fold (from 15.4% to 60.6%). Clindamycin
      resistance did not show evolution, whereas tetracycline nonsusceptibility
      decreased from 43.3% in 2003-2004 to 20.7% in 2007-2009. Except for one (0.5%) P.
      oralis strain with intermediate susceptibility to BL/BLIs, the other strains were
      susceptible to the agents. In conclusion, in Prevotella strains from patients
      with head-and-neck infections, the resistance rate to penicillin increased, that
      to clindamycin remained stable and the nonsusceptibility rate to tetracycline
      decreased during the period. Activity against >99% of Prevotella strains was
      observed with metronidazole and BL/BLIs. The penicillin resistance and
      tetracycline nonsusceptibility were associated with the year of study, national
      antibiotic consumption and possibly with previous treatment (for tetracycline).
      The evolution of penicillin resistance in Prevotella strains was highly dynamic.

PMID- 20670688
TI  - The other Janus face of Qa-1 and HLA-E: diverse peptide repertoires in times of
      stress.
AB  - The non-polymorphic MHC molecule Qa-1 and its human counterpart HLA-E present
      monomorphic signal peptides to innate receptors and thereby regulate lymphocyte
      activity. Under stress, this peptide content is replaced with a surprisingly
      diverse repertoire of novel peptides that are associated with heat-shock
      proteins, infectious agents or antigen processing defects.

PMID- 20670689
TI  - Pneumococcal proteins PspA and PspC induce CXCL8 production in human neutrophils:
      implications in pneumococcal infections.
AB  - Surface-exposed pneumococcal virulence proteins pneumococcal surface protein A
      (PspA) and pneumococcal surface protein C (PspC) play important roles in the
      pathogenesis of invasive pneumococcal diseases. Human neutrophils are principle
      antimicrobial effector cells of the innate and adaptive immune systems. In this
      study, we investigated the effects of PspA and PspC on the up-regulation of
      chemokine CXCL8 in human neutrophils, and characterized the underlying
      intracellular signaling pathways. Both PspA and PspC were found to induce the
      release of newly synthesized CXCL8. Synergistic effect was observed in the
      combined treatment of PspA and PspC on the release of CXCL8. Products from PspA
      deficient or PspC-deficient mutant pneumococcus that did not express PspA or PspC
      induced significantly less release of CXCL8 than wild type pneumococcus. Both
      PspA and PspC could activate p38 MAPK and NF-kappaB pathways in neutrophils,
      while inhibition of NF-kappaB and p38 MAPK could suppress the release of CXCL8
      from neutrophils induced by PspA and PspC. Together, our results demonstrated
      that the induction of CXCL8 in human neutrophils activated by PspA and PspC was
      regulated by p38 MAPK and NF-kappaB pathways.

PMID- 20670690
TI  - Influence of leishmanolysin-like molecules of Herpetomonas samuelpessoai on the
      interaction with macrophages.
AB  - Monoxenous trypanosomatids usually have an invertebrate as the only host in their
      life cycles, however, they have been found repeatedly in plants and/or mammals.
      To succeed in colonizing a vertebrate host, the parasite must quickly adapt to
      drastic changes in the environment (e.g. temperature), which reflect the
      conditions found in the insect and mammalian hosts. Leishmanolysin is a
      metalloprotease ubiquitously distributed in trypanosomatids, playing a myriad of
      functions. In Herpetomonas samuelpessoai, an insect trypanosomatid, the
      leishmanolysin-like molecule was implicated in the nutrition and insect adhesion.
      Herein, we showed that leishmanolysin expression is equally expressed in H.
      samuelpessoai parasites submitted to insect (26  degrees C) and mammalian (37 
      degrees C) temperatures. Also, the parasites grown in both temperatures
      interacted at similar rates with macrophages. Finally, we showed that
      leishmanolysin is involved in crucial steps in the interaction of H.
      samuelpessoai cells with macrophages, since the treatment with either anti
      leishmanolysin antibodies or metalloprotease inhibitor 1,10-phenanthroline
      significantly reduced the association index. Similarly, the treatment of the
      macrophages with purified leishmanolysin promoted a powerful reduction in the
      association index, suggesting the direct involvement of macrophage receptors.
      These results suggest that H. samuelpessoai leishmanolysin molecules are not
      modulated by temperature and are involved in the interaction with mammalian
      cells.

PMID- 20670691
TI  - CD44-independent activation of the Met signaling pathway by HGF and InlB.
AB  - Listeria monocytogenes is a facultative intracellular Gram-positive bacterium
      responsible for listeriosis. It is able to invade, survive and replicate in
      phagocytic and non-phagocytic cells. The L. monocytogenes surface protein InlB
      interacts with c-Met, the hepatocyte growth factor (HGF) receptor, inducing
      bacterial internalization in numerous non-phagocytic cells. As InlB and HGF are
      known to trigger similar signaling pathways upon c-Met activation, we
      investigated the role of CD44, and more specifically its isoform CD44v6, in
      bacterial internalization in non-phagocytic cells. Indeed, CD44, the hyaluronic
      acid transmembrane receptor, and more specifically its isoform CD44v6 have been
      reported as necessary for the activation of c-Met upon the interaction with
      either the endogenous ligand HGF or the L. monocytogenes surface protein InlB.
      Our results demonstrate that, in the cell lines that we used, CD44 receptors play
      no role in the activation of c-Met, neither during L. monocytogenes entry, nor
      upon HGF activation. Furthermore, none of the CD44 isoforms was recruited at the
      L. monocytogenes entry site, and depletion by siRNA of total CD44 or of CD44v6
      isoform did not reduce bacterial infections. Conversely, the overexpression of
      CD44 or CD44v6 had no significant effect on L. monocytogenes internalization.
      Together our results reveal that the activation of c-Met can be largely CD44
      independent.

PMID- 20670692
TI  - Attachment of flagellum to the cell body is important to the kinetics of
      transferrin uptake by Trypanosoma cruzi.
AB  - The flagellar pocket and the cytostome are surface domains of Trypanosoma cruzi
      epimastigote involved in acquisition of nutrients. The cytostome is physically
      connected to the flagellar complex. To investigate if this association plays a
      role in endocytosis in T. cruzi, the endocytic activity in wild type and gp72
      null mutant (flagellum-cell body attachment region is absent) epimastigotes was
      compared. Both wild type and mutant cells were incubated with transferrin
      conjugated with Alexa 543 or gold particles over different time periods and
      thereafter qualitatively and quantitatively analyzed by flow cytometry and
      transmission electron microscopy. Flow cytometry analysis showed a reduction in
      transferrin uptake by null mutant after 30 min of incubation. In addition, at
      this time period, signals detected by fluorescence microscopy were slightly lower
      in null mutant cells. At lower incubation times, no differences between wild type
      and mutant epimastigotes could be observed. Quantitative data obtained by
      morphometric and flow cytometry analysis suggested that the speed of the
      endocytic process in the null mutant was similar to wild type cells, although
      null mutants were not able to bind cargo and therefore internalize as much as
      wild type epimastigotes. Our observations suggest that the physical association
      between cytostome and the flagellar complex plays a role in endocytosis
      efficiency by epimastigotes of T. cruzi.

PMID- 20670693
TI  - Automatically extracting information needs from complex clinical questions.
AB  - OBJECTIVE: Clinicians pose complex clinical questions when seeing patients, and
      identifying the answers to those questions in a timely manner helps improve the
      quality of patient care. We report here on two natural language processing
      models, namely, automatic topic assignment and keyword identification, that
      together automatically and effectively extract information needs from ad hoc
      clinical questions. Our study is motivated in the context of developing the
      larger clinical question answering system AskHERMES (Help clinicians to Extract
      and aRrticulate Multimedia information for answering clinical quEstionS). DESIGN
      AND MEASUREMENTS: We developed supervised machine-learning systems to
      automatically assign predefined general categories (e.g. etiology, procedure, and
      diagnosis) to a question. We also explored both supervised and unsupervised
      systems to automatically identify keywords that capture the main content of the
      question. RESULTS: We evaluated our systems on 4654 annotated clinical questions
      that were collected in practice. We achieved an F1 score of 76.0% for the task of
      general topic classification and 58.0% for keyword extraction. Our systems have
      been implemented into the larger question answering system AskHERMES. Our error
      analyses suggested that inconsistent annotation in our training data have hurt
      both question analysis tasks. CONCLUSION: Our systems, available at
      http://www.askhermes.org, can automatically extract information needs from both
      short (the number of word tokens <20) and long questions (the number of word
      tokens >20), and from both well-structured and ill-formed questions. We speculate
      that the performance of general topic classification and keyword extraction can
      be further improved if consistently annotated data are made available.

PMID- 20670694
TI  - Male sex and smoking have a larger impact on the prevalence of colorectal
      neoplasia than family history of colorectal cancer.
AB  - BACKGROUND & AIMS: Screening recommendations for colorectal cancer (CRC) commonly
      take family history but no other risk factors into account. We compared and
      assessed risk factors of colorectal polyps in a large population undergoing
      screening colonoscopy. METHODS: We conducted a population-based cross-sectional
      study that included 3349 subjects, 55 years or older (mean ages of men and women,
      63.6 and 63.4 years, respectively), who underwent colonoscopy for the first time
      within the nationwide colonoscopy screening program in Germany. We calculated
      prevalences of colorectal polyps and estimated multivariate prevalence ratios
      (PRs) and population attributable fractions (PAFs). RESULTS: Overall, 654
      subjects had hyperplastic polyps (20%), 675 had non-advanced adenomas (20%), 343
      had advanced adenomas (10%), and 40 had CRC (1%). Risk factor prevalences and
      adjusted PRs were higher for male gender and smoking than for family history of
      CRC. PAFs for prevalence of non-advanced and advanced neoplasia were highest for
      male gender (23% and 23%, respectively), followed by smoking (7% and 9%,
      respectively), and family history of CRC (2% and 4%, respectively). CONCLUSIONS:
      Male gender and smoking have a larger impact on the prevalence of colorectal
      neoplasia than family history, suggesting an extensive evaluation of additional
      risk stratification in population-based screening, particularly by sex.

PMID- 20670695
TI  - The caudal solitary complex is a site of central CO(2) chemoreception and
      integration of multiple systems that regulate expired CO(2).
AB  - The solitary complex is comprised of the nucleus tractus solitarius (NTS,
      sensory) and dorsal motor nucleus of the vagus (DMV, motor), which functions as
      an integrative center for neural control of multiple systems including the
      respiratory, cardiovascular and gastroesophageal systems. The caudal NTS-DMV is
      one of the several sites of central CO(2) chemoreception in the brain stem. CO(2)
      chemosensitive neurons are fully responsive to CO(2) at birth and their
      responsiveness seems to depend on pH-sensitive K(+) channels. In addition,
      chemosensitive neurons are highly sensitive to conditions such as hypoxia (e.g.,
      neural plasticity) and hyperoxia (e.g., stimulation), suggesting they employ
      redox and nitrosative signaling mechanisms. Here we review the cellular and
      systems physiological evidence supporting our hypothesis that the caudal NTS-DMV
      is a site for integration of respiratory, cardiovascular and gastroesophageal
      systems that work together to eliminate CO(2) during acute and chronic
      respiratory acidosis to restore pH homeostasis.

PMID- 20670696
TI  - Associated malformations in patients with limb reduction deficiencies.
AB  - Infants with limb reduction deficiencies (LRD) often have other associated
      congenital malformations. The purpose of this investigation was to assess the
      prevalence and the types of associated malformations in a defined population.
      This study included special strengths: each affected child was examined by a
      geneticist, all elective terminations were ascertained, and the surveillance for
      malformations was continued until 1 year of age. The associated malformations in
      infants with LRD were collected in all livebirths, stillbirths and terminations
      of pregnancy during 25 years in 347,810 consecutive births in the area covered by
      our population based registry of congenital malformations. Of the 271 LRD infants
      born during this period, representing a prevalence of 7.8 per 10,000, 57.9% had
      associated malformations. There were 17(6.3%) patients with chromosomal
      abnormalities including 10 trisomies 18, and 62 (22.9%) nonchromosomal recognized
      dysmorphic conditions. There were no predominant recognized dysmorphic
      conditions, but VA(C)TER(L) association. However numerous recognized dysmorphic
      conditions were registered including Poland, ectrodactyly-ectodermal dysplasia
      clefting, oral-facial-digital, Klippel-Trenaunay-Weber, oculo-auriculo-vertebral
      defect spectrum, CHARGE, Townes-Brocks, Moebius, Du Pan, Smith-Lemli-Opitz,
      hypoglossia-hypodactyly, amniotic band, De Lange, Rubinstein-Taybi, Fanconi,
      radius aplasia- thrombocytopenia, Roberts, Holt-Oram, and fetal
      diethylstilbestrol. Seventy eight (28.8%) of the patients were multiply, non
      syndromic, non chromosomal malformed infants (MCA). Malformations in the cardiac
      system, in the genital system, and in the central nervous system were the most
      common other malformations, 11.4%, 9.4%, and 7.7% of the associated
      malformations, respectively, followed by malformations in the renal system
      (4.8%), and in the digestive system (4.6%). Prenatal diagnosis was performed in
      48.4% of dysmorphic syndromes with LRD. The overall prevalence of associated
      malformations, which was more than one in two infants, emphasizes the need for a
      thorough investigation of infants with LRD.A routine screening for other
      malformations especially cardiovascular system, urogenital system, central
      nervous system, and digestive system may be considered in infants and in fetuses
      with LRD.

PMID- 20670697
TI  - De novo 325 kb microdeletion in chromosome band 10q25.3 including ATRNL1 in a boy
      with cognitive impairment, autism and dysmorphic features.
AB  - We provide the first description of a patient with a heterozygous deletion of the
      Attractin-like (ATRNL1) gene. The patient presented with a novel and distinctive
      phenotype comprising dysmorphic facial appearance, ventricular septal defect, toe
      syndactyly, radioulnar synostosis, postnatal growth retardation, cognitive
      impairment with autistic features, and ataxia. A 325 kb de novo deletion in
      ATRNL1 was demonstrated using SNP microarray and confirmed by FISH analysis using
      BAC probes. Sequence analysis of the undeleted allele did not identify any
      alterations, suggesting that the phenotype was the result of haploinusfficiency.
      ATRNL1 and its paralog ATRN are highly conserved transmembrane proteins thought
      to be involved in cell adhesion and signalling events. The phenotype of mice with
      homozygous Atrn mutations overlaps considerably with the features observed in our
      patient. We therefore postulate that our patient's phenotype is caused by the
      deletion of ATRNL1, and provide further insight into the role of ATRNL1 in human
      development.

PMID- 20670698
TI  - Epithelial plasticity, cancer stem cells and bone metastasis formation.
AB  - Acquisition of an invasive phenotype of cancer cells in primary tumors is an
      absolute requirement for bone metastasis. The majority of bone metastases is
      derived from epithelial cancers, particularly those of the breast and prostate.
      Accumulating evidence suggest that transformed epithelial cells can activate
      embryonic programs of epithelial plasticity and switch from a sessile, epithelial
      phenotype to a motile, mesenchymal phenotype also referred to as epithelial-to
      mesenchymal transition (EMT). Induction of EMT can, therefore, lead to invasion
      of surrounding stroma, intravasation, dissemination and colonization of distant
      sites. In bone/bone marrow disseminated tumor cells can partially regain their
      original epithelial characteristics via a mesenchymal-to-epithelial transition
      (MET) as glandular structures in bone metastasis are frequently observed. To
      date, the importance of epithelial plasticity in cancer cells disseminated to the
      bone/bone marrow microenvironment has remained largely elusive. Interestingly, a
      number of growth factors that play a prominent role in EMT induction in the
      primary tumor have been identified as important stimulators of skeletal
      metastasis formation. Recent studies have demonstrated that EMT may render cancer
      cells with properties of stem cells, which in turn can lead to escape from immune
      surveillance, increased resistance to apoptosis, diminished senescence and, last
      but-not least, therapy resistance. This review will discuss current concepts
      regarding the role of epithelial plasticity in the multistep processes of bone
      metastasis, the issue of minimal residual disease, cancer stem cells and the
      importance of EMT in the development of novel targeted drug therapy.

PMID- 20670699
TI  - Managing gout in the primary care setting: what you and your patients need to
      know.
AB  - The US prevalence of gout, a rapidly progressive inflammatory arthritic condition
      linked to serum uric acid levels, has grown in recent years, in part due to the
      increasing prevalence and incidence of predisposing factors in the population,
      such as metabolic syndrome, obesity, and the use of diuretics. Left untreated,
      gout can be debilitating and cause deformity. Although a definitive diagnosis
      requires joint aspiration, only approximately 11% of patients with suspected gout
      undergo this procedure, and a presumptive diagnosis based on patient medical
      history and presentation with characteristic symptoms and comorbidities is a
      reasonable guidelines-based approach that has utility in the primary care
      setting, where approximately 70% of all cases and nearly 3,000,000 visits occur.
      The therapeutic standard for patients with recurrent gout flares is urate
      lowering therapy (ULT), including allopurinol and the recently introduced
      febuxostat, the first new treatment for gout in 40 years. Although ULT must be
      taken consistently to sustain benefits, inadequate dosing and patient
      nonadherence or intolerance to therapy often lead to treatment failure. It is
      important that primary care clinicians understand gout diagnosis and therapeutic
      approaches and can communicate effectively with patients to improve treatment
      adherence. ONLINE ACCESS: http://cmeaccess.com/cme/ajm_gout_program/ This CME
      Multimedia Activity is also available through the Website of The American Journal
      of Medicine (www.amjmed.com). Click on the CME Multimedia Activity button in the
      navigation bar for full access.

PMID- 20670700
TI  - Diagnosis: the eyes have it.

PMID- 20670701
TI  - Diagnostic value of chest radiographs in bedridden patients with suspected
      pneumonia.

PMID- 20670703
TI  - Optimization of tissue oxygenation in critically ill Jehovah's Witness patients.

PMID- 20670705
TI  - Post-Lyme disease symptoms.

PMID- 20670707
TI  - Persistent symptoms following treatment of early Lyme disease: false hope?

PMID- 20670709
TI  - Subjective symptoms after treatment of Lyme disease.

PMID- 20670710
TI  - Cytomegalovirus infection: a potential threat to atrioventricular conduction?

PMID- 20670712
TI  - Loop diuretics for heart failure-associated hyponatremia.

PMID- 20670713
TI  - A new "hump".

PMID- 20670714
TI  - Not your otitis media 101.

PMID- 20670715
TI  - Learning to write: a personal reflection.

PMID- 20670716
TI  - The future of malpractice reform.

PMID- 20670717
TI  - Assessing the presence and severity of depression in subjects with comorbid
      coronary heart disease.
AB  - Our understanding of how depression alters the origin and course of coronary
      heart disease is derived from subjective methodologies. Many psychiatric
      instruments were not tested for reliability and validity in subjects with
      comorbid medical illness, particularly coronary heart disease. They largely use
      scales of categoric or ordinal variables. Instruments used to assess coronary
      heart disease are considerably more objective and often use interval variables.
      By searching the websites of Circulation and the Journal of the American College
      of Cardiology, we entered the word "depression" on August 28, 2009. We ignored
      articles using "depression" in the context of cardiovascular concepts such as "ST
      segment depression." By searching articles dating back to 1995, we selected
      publications that studied the prognostic association of depression and coronary
      heart disease. There were 5 relevant publications: 3 from Circulation and 2 from
      the Journal of the American College of Cardiology. The methods used to assess
      coronary heart disease (specifically, myocardial infarction) are largely
      homogenous across the studies, but the methods used to assess depression are
      heterogeneous. Parameters used to diagnose myocardial infarction and determine
      its severity are precise, objective, and reliable, whereas those used to assess
      depression and its severity exhibit less precision and lack comparable
      objectivity and reliability. This mismatch may compromise our understanding of
      the link between coronary heart disease and depression in depressed patients with
      comorbid coronary heart disease. We propose using precise instruments to identify
      and quantitate coronary heart disease as outcome variables to assess psychiatric
      interventions and to better define depression in depressed patients with comorbid
      coronary heart disease. This should lead to a better understanding of the link
      between depression and comorbid coronary heart disease.

PMID- 20670718
TI  - Celiac disease diagnosis: simple rules are better than complicated algorithms.
AB  - Celiac disease is the only treatable autoimmune disease, provided that a correct
      diagnosis is achieved and a strict, lifelong gluten-free diet is implemented. The
      current diagnostic algorithm for celiac disease includes initial screening
      serological tests, followed by a confirmatory small intestinal biopsy showing the
      autoimmune insult typical of celiac disease. The biopsy, considered the
      diagnostic gold standard, has been recently questioned as a reliable and
      conclusive test for every case. Indeed, the wide variability of celiac disease
      related findings suggests that it is difficult to conceptualize the diagnostic
      process into rigid algorithms that do not always cover the clinical complexity of
      this disease. Instead we find clinically useful the shifting to a quantitative
      approach that can be defined as the "4 out of 5" rule: the diagnosis of celiac
      disease is confirmed if at least 4 of the following 5 criteria are satisfied:
      typical symptoms of celiac disease; positivity of serum celiac disease
      immunoglobulin, A class autoantibodies at high titer; human leukocyte antigen
      (HLA)-DQ2 or DQ8 genotypes; celiac enteropathy at the small bowel biopsy; and
      response to the gluten-free diet.

PMID- 20670719
TI  - Sweet's syndrome.

PMID- 20670720
TI  - Malignant mimicry.

PMID- 20670721
TI  - A diagnosis in vein.

PMID- 20670722
TI  - Captain Ignose to the rescue.

PMID- 20670723
TI  - A toxic combination.

PMID- 20670724
TI  - Trouble in transit.

PMID- 20670725
TI  - Prevalence and characteristics of tinnitus among US adults.
AB  - BACKGROUND: Tinnitus is common; however, few risk factors for tinnitus are known.
      METHODS: We examined cross-sectional relations between several potential risk
      factors and self-reported tinnitus in 14,178 participants in the 1999-2004
      National Health and Nutrition Examination Surveys, a nationally representative
      database. We calculated the prevalence of any and frequent (at least daily)
      tinnitus in the overall US population and among subgroups. Logistic regression
      was used to calculate odds ratios (OR) and 95% confidence intervals (CI) after
      adjusting for multiple potential confounders. RESULTS: Approximately 50 million
      US adults reported having any tinnitus, and 16 million US adults reported having
      frequent tinnitus in the past year. The prevalence of frequent tinnitus increased
      with increasing age, peaking at 14.3% between 60 and 69 years of age. Non
      Hispanic whites had higher odds of frequent tinnitus compared with other
      racial/ethnic groups. Hypertension and former smoking were associated with an
      increase in odds of frequent tinnitus. Loud leisure-time, firearm, and
      occupational noise exposure also were associated with increased odds of frequent
      tinnitus. Among participants who had an audiogram, frequent tinnitus was
      associated with low-mid frequency (OR 2.37; 95% CI, 1.76-3.21) and high frequency
      (OR 3.00; 95% CI, 1.78-5.04) hearing impairment. Among participants who were
      tested for mental health conditions, frequent tinnitus was associated with
      generalized anxiety disorder (OR 6.07; 95% CI, 2.33-15.78) but not major
      depressive disorder (OR 1.58; 95% CI, 0.54-4.62). CONCLUSIONS: The prevalence of
      frequent tinnitus is highest among older adults, non-Hispanic whites, former
      smokers, and adults with hypertension, hearing impairment, loud noise exposure,
      or generalized anxiety disorder. Prospective studies of risk factors for tinnitus
      are needed.

PMID- 20670726
TI  - Blood pressure and outcomes in very old hypertensive coronary artery disease
      patients: an INVEST substudy.
AB  - BACKGROUND: Our understanding of the growing population of very old patients
      (aged >or=80 years) with coronary artery disease and hypertension is limited,
      particularly the relationship between blood pressure and adverse outcomes.
      METHODS: This was a secondary analysis of the INternational VErapamil SR
      Trandolapril STudy (INVEST), which involved 22,576 clinically stable hypertensive
      coronary artery disease patients aged >or=50 years. The patients were grouped by
      age in 10-year increments (aged >or=80, n=2180; 70-<80, n=6126; 60-<70, n=7602;
      <60, n=6668). Patients were randomized to either verapamil SR- or atenolol-based
      treatment strategies, and primary outcome was first occurrence of all-cause
      death, nonfatal myocardial infarction, or nonfatal stroke. RESULTS: At baseline,
      increasing age was associated with higher systolic blood pressure, lower
      diastolic blood pressure, and wider pulse pressure (P <.001). Treatment decreased
      systolic, diastolic, and pulse pressure for each age group. However, the very old
      retained the widest pulse pressure and the highest proportion (23.6%) with
      primary outcome. The adjusted hazard ratio for primary outcomes showed a J-shaped
      relationship among each age group with on-treatment systolic and diastolic
      pressures. The systolic pressure at the hazard ratio nadir increased with
      increasing age, highest for the very old (140 mm Hg). However, diastolic pressure
      at the hazard ratio nadir was only somewhat lower for the very old (70 mm Hg).
      Results were independent of treatment strategy. CONCLUSION: Optimal management of
      hypertension in very old coronary artery disease patients may involve targeting
      specific systolic and diastolic blood pressures that are higher and somewhat
      lower, respectively, compared with other age groups.

PMID- 20670727
TI  - Paradoxical preservation of vascular function in severe obesity.
AB  - BACKGROUND: Obesity is associated with a high risk of coronary artery disease
      morbidity and mortality. Yet, postmortem studies have shown that severely obese
      subjects exhibit smooth coronary arteries, thus suggesting that they may be
      protected from atherosclerosis. We assessed vascular function and its possible
      determinants in a cohort of normal-weight to severely obese insulin-sensitive
      subjects (body mass index [BMI] 23.2-49 kg/m(2)). METHODS: Seventy-one healthy,
      insulin-sensitive subjects (Homeostasis Model Assessment of Insulin Resistance
      index <2.5), divided into normal-weight (n = 13; BMI = 23.2 +/- 1.6), obese (n =
      35; BMI=32.6+/-2.5), and severely obese (n=23; BMI=49.0+/-7.9) groups, were
      enrolled. Vascular function was evaluated by flow-mediated dilation and carotid
      intima-media thickness. High-sensitivity C-reactive protein, leptin, adiponectin,
      vascular growth factors, and CD34+KDR+/CD133+ endothelial progenitor cells, known
      markers of vascular health/protection, also were measured. RESULTS: Flow-mediated
      dilation was higher in severely obese than in obese and normal-weight individuals
      (P=.019 and P=.011 respectively). Intima-media thickness was consistently lower
      in severely obese than in obese individuals (P=.040) and similar in severely
      obese and normal-weight individuals (P >.99). Levels of high-sensitivity C
      reactive protein and leptin were higher in severely obese than in obese and
      normal-weight individuals (high-sensitivity C-reactive protein: P=.018 and P=.05,
      respectively; leptin: P <.001 for both comparisons). CD34+KDR+ endothelial
      progenitor cells were significantly higher in severely obese versus obese
      individuals (P=.039). CONCLUSION: Our study demonstrates that vascular function
      is paradoxically better in severely obese than in obese subjects and similar to
      that found in normal-weight subjects. Despite higher levels of high-sensitivity C
      reactive protein and leptin, severely obese individuals may be partially
      protected from atherosclerosis, possibly by a greater mobilization of endothelial
      progenitor cells.

PMID- 20670728
TI  - Venous compression for prevention of postthrombotic syndrome: a meta-analysis.
AB  - PURPOSE: To determine the effectiveness of venous compression stockings or
      compression bandages on the reduction of postthrombotic syndrome in patients with
      deep venous thrombosis. METHODS: We attempted to identify all published trials in
      all languages identified by PubMed through June 2009. Meta-analysis was
      performed. RESULTS: Based on 5 randomized trials of patients with deep venous
      thrombosis comparing treatment with venous compression to controls, mild-to
      moderate postthrombotic syndrome occurred in 64 of 296 (22%) treated with venous
      compression, compared with 106 of 284 (37%) in controls (relative risk=0.52).
      Severe postthrombotic syndrome occurred in 14 of 296 (5%) treated, compared with
      33 of 284 (12%) controls (relative risk=0.38). Any postthrombotic syndrome
      occurred in 89 of 338 (26%) treated, compared with 150 of 324 (46%) controls
      (relative risk=0.54). CONCLUSION: Venous compression reduced the incidence of
      postthrombotic syndrome, particularly severe postthrombotic syndrome. Venous
      compression in patients with deep venous thrombosis would seem to be indicated
      for this purpose. There was, however, wide variation in the type of stockings
      used, time interval from diagnosis to application of stockings, and duration of
      treatment. Further investigation, therefore, is needed.

PMID- 20670729
TI  - Health insurance and cardiovascular disease risk factors.
AB  - BACKGROUND: Compared with those with health insurance, the uninsured receive less
      care for chronic conditions, such as hypertension and diabetes, and experience
      higher mortality. METHODS: We investigated the relations of health insurance
      status to the prevalence, treatment, and control of major cardiovascular disease
      risk factors-hypertension and elevated low-density lipoprotein (LDL) cholesterol
      among Framingham Heart Study (FHS) participants in gender-specific, age-adjusted
      analyses. Participants who attended the seventh Offspring cohort examination
      cycle (1998-2001) or the first Third Generation cohort examination cycle (2002
      2005) were studied. RESULTS: Among 6098 participants, 3.8% were uninsured at the
      time of the FHS clinic examination and ages ranged from 19 to 64 years. The
      prevalence of hypertension and elevated LDL cholesterol was similar for the
      insured and uninsured; however, the proportion of those who obtained treatment
      and achieved control of these risk factors was lower among the uninsured.
      Uninsured men and women were less likely to be treated for hypertension with odds
      ratios for treatment of 0.19 (95% confidence interval [CI], 0.07-0.56) for men
      and 0.31 (95% CI, 0.12-0.79) for women. Among men, the uninsured were less likely
      to receive treatment or achieve control of elevated LDL cholesterol than the
      insured, with odds ratios of 0.12 (95% CI, 0.04-0.38) for treatment and 0.17 (95%
      CI, 0.05-0.56) for control. CONCLUSION: The treatment and control of hypertension
      and hypercholesterolemia are lower among uninsured adults. Increasing the
      proportion of insured individuals may be a means to improve the treatment and
      control of cardiovascular disease risk factors and to reduce health disparities.

PMID- 20670730
TI  - Depression and incident diabetic foot ulcers: a prospective cohort study.
AB  - OBJECTIVE: To test whether depression is associated with an increased risk of
      incident diabetic foot ulcers. METHODS: The Pathways Epidemiologic Study is a
      population-based prospective cohort study of 4839 patients with diabetes in 2000
      2007. The present analysis included 3474 adults with type 2 diabetes and no prior
      diabetic foot ulcers or amputations. Mean follow-up was 4.1 years. Major and
      minor depression assessed by the Patient Health Questionnaire-9 were the
      exposures of interest. The outcome of interest was incident diabetic foot ulcers.
      We computed the hazard ratio and 95% confidence interval (CI) for incident
      diabetic foot ulcers, comparing patients with major and minor depression with
      those without depression and adjusting for sociodemographic characteristics,
      medical comorbidity, glycosylated hemoglobin, diabetes duration, insulin use,
      number of diabetes complications, body mass index, smoking status, and foot self
      care. Sensitivity analyses also adjusted for peripheral neuropathy and peripheral
      arterial disease as defined by diagnosis codes. RESULTS: Compared with patients
      without depression, patients with major depression by Patient Health
      Questionnaire-9 had a 2-fold increase in the risk of incident diabetic foot
      ulcers (adjusted hazard ratio 2.00; 95% CI, 1.24-3.25). There was no
      statistically significant association between minor depression by Patient Health
      Questionnaire-9 and incident diabetic foot ulcers (adjusted hazard ratio 1.37;
      95% CI, 0.77-2.44). CONCLUSION: Major depression by Patient Health Questionnaire
      9 is associated with a 2-fold higher risk of incident diabetic foot ulcers.
      Future studies of this association should include better measures of peripheral
      neuropathy and peripheral arterial disease, which are possible confounders or
      mediators.

PMID- 20670731
TI  - Early creatinine shifts predict contrast-induced nephropathy and persistent renal
      damage after angiography.
AB  - PURPOSE: The purpose of this study was to evaluate incidence and predictors of
      contrast-induced nephropathy after coronary angiography and interventions, and to
      assess renal function at 30 days. The prognostic value of any early shift of
      serum creatinine compared with baseline was investigated; such measurement, being
      a delta, is largely independent of creatinine variations. METHODS: There were 216
      patients at risk for contrast-induced nephropathy prospectively evaluated at
      baseline and at 12, 24, and 48 hours after exposure to contrast media, and 190
      (88%) evaluated 1 month after discharge. RESULTS: Contrast-induced nephropathy
      occurred in 39 patients (18%), and 30-day renal damage was detected in 15 (7%).
      Contrast media/kg volume predicted contrast-induced nephropathy (P=.002), and
      percentage change of creatinine 12 hours from baseline was significantly higher
      in patients with nephropathy (P <.001). At multivariate analysis, percentage
      change of creatinine 12 hour-basal was the best predictor of nephropathy (P
      <.001). A 5% increase of its value yielded 75% sensitivity and 72% specificity
      (area under the curve 0.80; odds ratio 7.37; 95% confidence interval, 3.34-16.23)
      for early contrast-induced nephropathy detection. Furthermore, it strongly
      correlated with the development of renal impairment at 30 days (P=.002;
      sensitivity 87%, specificity 70%; area under the curve 0.85; odds ratio 13.29;
      95% confidence interval, 2.91-60.64). CONCLUSION: Minimal elevations of serum
      creatinine at 12 hours are highly predictive of contrast-induced nephropathy and
      30-day renal damage after exposure to contrast media.

PMID- 20670733
TI  - No effect of selenium supplementation on serum glucose levels in men with
      prostate cancer.
AB  - BACKGROUND: Literature indicates a relationship between selenium supplementation
      and risk of diabetes. However, because these data are inconclusive, we
      investigated the effect of selenium supplementation on serum glucose levels in
      men with prostate cancer enrolled in a clinical trial testing of the effect of
      selenium on prostate cancer progression. METHODS: Subjects were randomized to
      receive placebo (n=46), selenium 200 microg/day (n=47), and selenium 800
      microg/day (n=47). Serum glucose levels were obtained every 6 months for up to 5
      years. Longitudinal analysis was carried out to assess whether rate of change of
      serum glucose levels was significantly different in the selenium-supplemented
      groups as compared with placebo. Sensitivity analyses were performed to assess
      the robustness of findings. RESULTS: Changes in serum glucose levels during the
      course of the trial were not statistically significantly different as compared
      with placebo for the selenium 200 microg/day (P=.56) or selenium 800 microg/day
      (P=.91) treatment groups. CONCLUSION: These results do not support a relationship
      between selenium supplementation and changes in serum glucose levels.
      Recommendations about selenium supplementation and risk of diabetes will require
      more definitive studies.

PMID- 20670732
TI  - Age disparity in the dissemination of imatinib for treating chronic myeloid
      leukemia.
AB  - BACKGROUND: Imatinib is a highly effective treatment for chronic myeloid
      leukemia. It was approved by the Food and Drug Administration in 2001 and
      thereafter rapidly became front-line therapy. This study characterized the
      prevailing chronic myeloid leukemia therapies in the United States and assessed
      the impact of imatinib on chronic myeloid leukemia survival and mortality rates
      in the general population. METHODS: Investigators with the National Cancer
      Institute's Patterns of Care study reviewed medical records and queried
      physicians regarding therapy for 423 patients with chronic myeloid leukemia
      diagnosed in 2003 who were randomly selected from cancer registries in the
      Surveillance, Epidemiology, and End Results Program. Characteristics associated
      with the receipt of imatinib were documented, as were survival differences
      between those who received imatinib and those who did not. Population-based data
      were used to assess chronic myeloid leukemia survival and mortality rates in time
      periods before and after the introduction of imatinib. RESULTS: Imatinib was
      administered to 76% of patients in the Patterns of Care study. Imatinib use was
      inversely associated with age: 90%, 75%, and 46% for patients ages 20 to 59
      years, 60 to 79 years, and 80 or more years, respectively. Elderly patients who
      received imatinib survived significantly longer than those who did not. After
      adjusting for age, imatinib use did not vary significantly by race/ethnicity,
      socioeconomic status, urban/rural residence, presence of comorbid conditions, or
      insurance status. Overall, chronic myeloid leukemia survival in the Surveillance,
      Epidemiology, and End Results population improved, and mortality in the United
      States declined dramatically during the period when imatinib became widely
      available; these improvements diminished with increasing age. CONCLUSION: Age
      disparities in treatment with imatinib likely contributed to worse survival for
      many elderly patients with chronic myeloid leukemia.

PMID- 20670734
TI  - AAIM Report on Master Teachers and Clinician Educators Part 1: needs and skills.

PMID- 20670735
TI  - William Carlos Williams and Mikhail Bulgakov on feeling versus reason.

PMID- 20670736
TI  - Defining authorship for group studies.

PMID- 20670737
TI  - Variety, variability and veracity: macular thickness and reproducibility among
      optical coherence tomography systems.

PMID- 20670738
TI  - Screening and managing eye disease in 2010: an Asian perspective.

PMID- 20670739
TI  - Nanomedicine in ophthalmology: the new frontier.
AB  - PURPOSE: To review the fields of nanotechnology and nanomedicine as they relate
      to the development of treatments for vision-threatening disorders. DESIGN:
      Perspective following literature review. METHODS: Analysis of relevant
      publications in the peer-reviewed scientific literature. RESULTS: Nanotechnology
      involves the creation and use of materials and devices at the size scale of
      intracellular structures and molecules and involves systems and constructs on the
      order of <100 nm. The aim of nanomedicine is the comprehensive monitoring,
      control, construction, repair, defense, and improvement of human biological
      systems at the molecular level, using engineered nanodevices and nanostructures,
      operating massively in parallel at the single cell level, ultimately to achieve
      medical benefit. The earliest impact of nanomedicine is likely to involve the
      areas of biopharmaceuticals (eg, drug delivery, drug discovery), implantable
      materials (eg, tissue regeneration scaffolds, bioresorbable materials),
      implantable devices (eg, intraocular pressure monitors, glaucoma drainage
      valves), and diagnostic tools (eg, genetic testing, imaging, intraocular pressure
      monitoring). Nanotechnology will bring about the development of regenerative
      medicine (ie, replacement and improvement of cells, tissues, and organs),
      ultrahigh-resolution in vivo imaging, microsensors and feedback devices, and
      artificial vision. "Regenerative nanomedicine," a new subfield of nanomedicine,
      uses nanoparticles containing gene transcription factors and other modulating
      molecules that allow for the reprogramming of cells in vivo. CONCLUSIONS:
      Nanotechnology already has been applied to the measurement and treatment of
      different disease states in ophthalmology (including early- and late-stage
      disease), and many additional innovations will occur during the next century.

PMID- 20670740
TI  - Bevacizumab vs ranibizumab for age-related macular degeneration: early results of
      a prospective double-masked, randomized clinical trial.

PMID- 20670742
TI  - Macular thickness in diabetic subjects without retinopathy.

PMID- 20670744
TI  - Glaucoma medications in the Tube versus Trabeculectomy Study.

PMID- 20670746
TI  - Quality of cataract surgery.

PMID- 20670747
TI  - Keratoprosthesis in China.

PMID- 20670748
TI  - [Endovascular treatment in acute ischemic stroke].

PMID- 20670752
TI  - Proceedings of the International Workshop on Enhanced Data Generated by
      Electrons. Foreword.

PMID- 20670753
TI  - Snakelike aortic right ventricular tunnel with anomalous origin of left main
      coronary artery in an adult woman.

PMID- 20670754
TI  - Minimally-invasive valve surgery.
AB  - Minimally-invasive approaches have become increasingly important in cardiac valve
      surgery. Smaller incisions have become commonplace in many major centers. We
      reviewed the existing literature and present the current state-of-the-art of
      minimally-invasive valve operations in this paper.

PMID- 20670755
TI  - Randomized comparison of eptifibatide versus abciximab in primary percutaneous
      coronary intervention in patients with acute ST-segment elevation myocardial
      infarction: results of the EVA-AMI Trial.
AB  - OBJECTIVES: The aim of this study was to compare eptifibatide and abciximab as
      adjuncts to primary percutaneous coronary intervention (PCI). BACKGROUND: The
      glycoprotein (GP) IIb/IIIa receptor inhibitor abciximab as adjunct to primary PCI
      in patients with ST-segment elevation myocardial infarctions has been shown to
      reduce ischemic complications and improve clinical outcomes. So far, no trial has
      been performed to compare the efficacy of another GP IIb/IIIa receptor inhibitor,
      eptifibatide, and abciximab in primary PCI. METHODS: A total of 427 patients with
      ST-segment elevation myocardial infarctions <12 h and planned primary PCI were
      randomized to double-bolus eptifibatide (n = 226) followed by a 24-h infusion or
      single-bolus abciximab (n = 201) followed by a 12-h infusion. In this
      noninferiority trial, the primary end point was the incidence of complete (> or
      =70%) ST-segment resolution (STR) 60 min after PCI, a measure of myocardial
      reperfusion. The assumption was a 60% complete STR rate in the abciximab group.
      The noninferiority margin was set to 15%. RESULTS: The incidence of complete STR
      at 60 min after PCI in the intention-to-treat analysis was 62.6% after
      eptifibatide and 56.3% after abciximab (adjusted difference: 7.1%; 95% confidence
      interval: 2.7% to 17.0%). All-cause mortality 6.2% versus 4.5% (p = 0.50);
      reinfarction 0.4% versus 3.5% (p = 0.03); target vessel revascularization 4.4%
      versus 6.5% (p = 0.40); the combined end point of death, nonfatal reinfarction,
      and target vessel revascularization 10.6% versus 10.9% (p = 0.90); stroke 0.5%
      versus 0.5% (p = 1.00) after 6 months; and Thrombolysis In Myocardial Infarction
      major bleeding complications 4.0% versus 2.0% (p = 0.20) after 30 days were
      observed after eptifibatide and abciximab, respectively. CONCLUSIONS:
      Eptifibatide as an adjunct to primary PCI is equally as effective as abciximab
      with respect to STR. (Efficacy of Eptifibatide Compared to Abciximab in Primary
      Percutaneous Coronary Intervention [PCI] for Acute ST Elevation Myocardial
      Infarction [STEMI]; NCT00426751).

PMID- 20670756
TI  - Eptifibatide is noninferior to abciximab in primary percutaneous coronary
      intervention: results from the SCAAR (Swedish Coronary Angiography and
      Angioplasty Registry).
AB  - OBJECTIVES: The aim of this study was to test the noninferiority of eptifibatide
      relative to abciximab in patients with ST-segment elevation myocardial infarction
      (STEMI) treated with primary percutaneous coronary intervention (PCI).
      BACKGROUND: Glycoprotein IIb/IIIa inhibitors are recommended by international
      guidelines in patients with acute coronary syndromes undergoing PCI. Abciximab is
      recommended with a higher level of evidence than eptifibatide in patients with
      STEMI. No large, prospective, randomized trial comparing abciximab and
      eptifibatide has been published. METHODS: All (n = 11,479) STEMI patients in
      Sweden who underwent primary PCI and received either eptifibatide or abciximab
      from 2004 to 2007 were derived from the SCAAR (Swedish Coronary Angiography and
      Angioplasty Registry). The primary end point was death or myocardial infarction
      (MI) during 1-year follow-up, with adjustment for baseline differences with a
      multivariate logistic regression analysis including propensity score. The pre
      specified noninferiority margin was set to 1.29. RESULTS: The combined end point
      occurred in 353 of 2,355 patients (15.0%) treated with eptifibatide and in 1,432
      of 9,124 patients (15.7%) treated with abciximab. The unadjusted odds ratio (OR)
      for eptifibatide versus abciximab was 0.95 (95% confidence interval [CI]: 0.84 to
      1.08). Multivariate adjustment (n = 11,317) confirmed noninferiority, with an OR
      of 0.94 (95% CI: 0.82 to 1.09). The adjusted secondary end points of death and MI
      separately also showed noninferiority, with ORs of 0.99 (95% CI: 0.82 to 1.19)
      and 0.88 (95% CI: 0.73 to 1.05), respectively. CONCLUSIONS: This large registry
      study suggests that eptifibatide is noninferior to abciximab in patients with
      STEMI undergoing primary PCI with respect to death or MI during 1 year, thereby
      supporting the use of either drug in clinical practice.

PMID- 20670757
TI  - The glycoprotein IIb/IIIa inhibitor wars: an update.

PMID- 20670758
TI  - Gene dosage of the common variant 9p21 predicts severity of coronary artery
      disease.
AB  - OBJECTIVES: The purpose of this study was to test the hypothesis that 9p21 gene
      dosage determines the severity of coronary artery disease (CAD). BACKGROUND: The
      9p21 locus is the first common genetic variant to associate with risk of CAD
      and/or myocardial infarction in multiple studies. METHODS: A cross-sectional
      study examined nondiabetic patients with CAD defined by coronary angiography to
      have at least 1 epicardial stenosis >50%. In all, 950 patients with early onset
      CAD (age 56.1 +/- 9.6 years) and an independent sample of 764 patients with late
      onset CAD (age 70.0 +/- 8.0 years) were enrolled from the cardiac catheterization
      laboratories at the University of Ottawa Heart Institute from April 15, 2006, to
      August 15, 2008, and genotyped for the single nucleotide polymorphism rs1333049
      9p21 risk variant. Angiographers were blinded to genotype. The association
      between 9p21 risk genotype and the proportion of patients with 3-vessel disease,
      1-vessel disease, left main trunk disease, and coronary artery bypass graft
      surgery was tested, as was its association with the modified Gensini and Duke
      coronary scoring indexes. RESULTS: Among younger CAD cases, 3-vessel disease
      demonstrated a strong, direct association with 9p21 gene dosage (p = 4.26 x 10(
      4)). Conversely, 1-vessel disease demonstrated a strong inverse association with
      increasing gene dosage (p = 2.41 x 10(-5)). In the replication sample, gene
      dosage also predicted 3-vessel disease (p = 6.51 x 10(-6)). Left main trunk
      disease and coronary artery bypass graft surgery demonstrated a direct strong
      association with gene dosage (p = 3.66 x 10(-4)) and (p = 2.42 x 10(-2)),
      respectively. Gene dosage demonstrated a strong, direct association with both the
      modified Gensini (p < 0.0001) and modified Duke (p = 3 x 10(-4)) coronary scores.
      Risk variant 9p21 did not associate with myocardial infarction once stratified
      for disease severity. CONCLUSIONS: Gene dosage of the common risk variant 9p21
      predicts the severity of coronary atheromatous burden.

PMID- 20670759
TI  - The 9p21 locus and coronary heart disease: initiator, promoter, or precipitator?

PMID- 20670760
TI  - STICH (Surgical Treatment for Ischemic Heart Failure) trial enrollment.
AB  - OBJECTIVES: The aim of this study was to assess the influence of enrolling site
      location and enrollment performance on the generalizability of STICH (Surgical
      Treatment for Ischemic Heart Failure) trial results. BACKGROUND: The
      international STICH trial seeks to define the role of cardiac surgery for
      patients with ischemic cardiomyopathy. METHODS: Baseline characteristics of 2,136
      randomized STICH patients were entered into a multivariate equation created using
      the Duke Databank for Cardiovascular Diseases to predict their 5-year risk for
      death without cardiac surgery. Patients ordered by increasing predicted risk were
      assigned to 1 of 32 risk at randomization (RAR) groups created to share one
      thirty-second of total predicted deaths. Numbers of patients sharing the same RAR
      group were compared between higher and lower enrolling site groupings and for
      countries tending to enroll high- or low-risk patients. RESULTS: Country of
      enrollment was a stronger determinant of risk diversity than site enrollment
      performance among patients enrolled at 127 sites in 26 countries. Mean RAR
      differences among countries ranged from 9.4 (Singapore) to 18.6 (Germany).
      However, 1,614 of 2,136 patients (76%) from countries enrolling lower-risk
      patients shared the same RAR group with patients from countries enrolling higher
      risk patients. Baseline characteristics responsible for risk differences of
      patients enrolled in the 2 country groupings were sufficiently similar to exert
      little influence on clinical decision making. CONCLUSIONS: STICH randomized
      patients are characterized by a continuous spectrum of risk, without discordant
      dominance from any site or country. Clinical site diversity promises to enhance
      the generalization of STICH trial results to a broad population of patients with
      ischemic cardiomyopathy. (Comparison of Surgical and Medical Treatment for
      Congestive Heart Failure and Coronary Artery Disease; NCT00023595).

PMID- 20670761
TI  - Clinical characteristics of patients undergoing surgical ventricular
      reconstruction by choice and by randomization.
AB  - OBJECTIVES: The aim of this study was to confirm the generalizability of the
      conclusions of the STICH (Surgical Treatment for Ischemic Heart Failure) trial.
      BACKGROUND: Surgical ventricular reconstruction (SVR) added to coronary artery
      bypass grafting (CABG) did not decrease death or cardiac hospitalization in STICH
      patients randomized to CABG with (n = 501) or without (n = 499) SVR. METHODS:
      Baseline clinical characteristics of 1,000 STICH SVR hypothesis patients and
      1,036 STICH-eligible Society of Thoracic Surgeons (STS) National Cardiac Database
      patients undergoing CABG plus SVR were entered into a multivariate model equation
      to predict a mortality that placed these 2,036 patients in 1 of 32 risk at
      randomization (RAR) groups. The number of patients in each RAR group profiled the
      risk of STICH treatment arms and of STICH and STS STICH-eligible patients.
      RESULTS: That 85% of the 1,000 STICH patients known to have no significant
      differences in baseline characteristics between the 2 treatment arms shared the
      same RAR group suggests that the RAR methodology has sufficient accuracy to
      compare RAR profiles of STICH and STS patients. RAR group was shared by 1,522 of
      2,036 STICH and STS STICH-eligible patients (75%) who underwent CABG plus SVR.
      Differences in baseline characteristics responsible for more low-risk STICH
      patients and more high-risk STS patients were modest. Cox proportional hazard
      ratios of 1,000 STICH patients in 3 RAR groups suggested by STICH and STS RAR
      differences showed no differential treatment effect on survival across the low-,
      intermediate-, and high-risk groups. CONCLUSIONS: The STICH conclusion of no
      benefit from adding SVR to CABG applies to a broad spectrum of CABG-eligible
      patients with ischemic cardiomyopathy. (Comparison of Surgical and Medical
      Treatment for Congestive Heart Failure and Coronary Artery Disease; NCT00023595).

PMID- 20670762
TI  - Evaluating clinical applicability: the STICH trial's findings.

PMID- 20670763
TI  - Minimally-invasive implantation of living tissue engineered heart valves: a
      comprehensive approach from autologous vascular cells to stem cells.
AB  - OBJECTIVES: The aim of this study was to demonstrate the feasibility of combining
      the novel heart valve replacement technologies of: 1) tissue engineering; and 2)
      minimally-invasive implantation based on autologous cells and composite self
      expandable biodegradable biomaterials. BACKGROUND: Minimally-invasive valve
      replacement procedures are rapidly evolving as alternative treatment option for
      patients with valvular heart disease. However, currently used valve substitutes
      are bioprosthetic and as such have limited durability. To overcome this
      limitation, tissue engineering technologies provide living autologous valve
      replacements with regeneration and growth potential. METHODS: Trileaflet heart
      valves fabricated from biodegradable synthetic scaffolds, integrated in self
      expanding stents and seeded with autologous vascular or stem cells (bone marrow
      and peripheral blood), were generated in vitro using dynamic bioreactors.
      Subsequently, the tissue engineered heart valves (TEHV) were minimally-invasively
      implanted as pulmonary valve replacements in sheep. In vivo functionality was
      assessed by echocardiography and angiography up to 8 weeks. The tissue
      composition of explanted TEHV and corresponding control valves was analyzed.
      RESULTS: The transapical implantations were successful in all animals. The TEHV
      demonstrated in vivo functionality with mobile but thickened leaflets. Histology
      revealed layered neotissues with endothelialized surfaces. Quantitative
      extracellular matrix analysis at 8 weeks showed higher values for
      deoxyribonucleic acid, collagen, and glycosaminoglycans compared to native
      valves. Mechanical profiles demonstrated sufficient tissue strength, but less
      pliability independent of the cell source. CONCLUSIONS: This study demonstrates
      the principal feasibility of merging tissue engineering and minimally-invasive
      valve replacement technologies. Using adult stem cells is successful, enabling
      minimally-invasive cell harvest. Thus, this new technology may enable a valid
      alternative to current bioprosthetic devices.

PMID- 20670764
TI  - Middle aortic syndrome percutaneous treatment with a balloon-expandable covered
      stent.

PMID- 20670765
TI  - President's page: The ACC encourages multi-pronged approach to radiation safety.

PMID- 20670766
TI  - Removal of contrast media from the coronary sinus attenuates renal injury after
      coronary angiography and intervention.

PMID- 20670767
TI  - Distinct patterns of autoantibodies against G-protein-coupled receptors in
      Chagas' cardiomyopathy and megacolon: their potential impact for early risk
      assessment in asymptomatic Chagas' patients.

PMID- 20670768
TI  - Quantity and quality in medical research.

PMID- 20670769
TI  - JUPITER "moderate CKD" subgroup is not truly "moderate" chronic kidney disease.

PMID- 20670770
TI  - New hope for chronic kidney disease patients after the JUPITER trial: myth or
      reality?

PMID- 20670772
TI  - Associated factors, timing, and technical aspects of late failure following open
      surgical aneurysm repairs.
AB  - OBJECTIVE: In contrast to endovascular repair (EVAR), the absence of rigorous
      imaging follow-up after open surgical repair (OSR) has rendered the perception
      that late failure (LF) is rare. Better understanding of associated factors with
      LF will help define OSR follow-up paradigms and perhaps alter initial repair
      strategy to facilitate treatment of LF. The aim of this study is to evaluate
      aspects of LF requiring intervention after OSR. METHODS: From 1998 to 2008, data
      were collected prospectively on 1097 patients who underwent an aortic
      endovascular repair. Patients undergoing intervention for LF contiguous with
      prior OSR were subjected to further analysis. The indication for reintervention
      was a maximal diameter >60 mm. Univariable and multivariable linear regression
      models were used to compare patients and disease variables (18 variables
      regarding age, comorbidities, family history, etiology, and extent) with time to
      LF. RESULTS: LF of open surgical aneurysm repair was identified in 104 (9.5%)
      patients. Mean aneurysm diameter was 72 +/- 12 mm. Mean age at first repair and
      time between the two repairs were 61.4 +/- 10.0 and 10.8 +/- 6.0 years,
      respectively. When compared with the 993 other patients whose EVAR was their
      primary repair, LF patients were significantly younger at the time of their first
      repair (61.4 +/- 10.0 vs 74.1 +/- 9.6 years; P < .00001) and more frequently had
      a family history of aneurysms (20% vs 7%; P = .001). They were also more likely
      to have presented with dissection, renal insufficiency, and manifestations of
      atherosclerosis. On multivariable analysis, patients with an initial incomplete
      OSR (aneurysm located in another aortic segment but not treated at the time of
      the primary repair), more extensive aneurysms (those involving the descending
      thoracic or the thoracoabdominal aorta), and older patients experienced earlier
      LF (P < .00001, .002, and .001, respectively). Although we were incapable of
      determining the incidence of LF after OSR, 34% of patients presenting with LF
      were regional to our center. CONCLUSION: Aneurysmal disease is an ongoing process
      potentially involving the entire aorta. Segments that appear normal prior to OSR
      of EVAR may be vulnerable to LF. We identified several groups of patients
      following OSR who mandate more aggressive follow-up given their propensity to
      present with LF. The threshold and strategies guiding reintervention in the
      setting of LF is dependent upon many factors relating to the structure and the
      morphology of the aorta and implanted graft, the type of anastomosis, and patient
      comorbidities. Therefore, surgeons should consider LF treatment options when
      planning an aneurysm repair in an effort to optimize any later interventions, and
      have specifically tailored follow-up paradigms.

PMID- 20670773
TI  - The impact of radiation dose exposure during endovascular aneurysm repair on
      patient safety.
AB  - OBJECTIVE: Endovascular aneurysm repair (EVAR) exposes patients to radiation
      during the procedure and in subsequent follow-up. The study goal was to calculate
      the radiation dose in our unit and compare it against other published data and
      national guidelines. METHODS: All EVAR procedures were identified from a
      prospectively maintained database. Radiation dose, screening time, and volume of
      intravenous contrast during the procedure were reviewed. Radiation exposure from
      subsequent computed tomography (CT) imaging was included in the overall exposure.
      Results are expressed as mean +/- standard deviation. RESULTS: From October 1998
      to October 2008, 320 elective patients underwent EVAR. Mean screening time was
      29.4 +/- 23.3 minutes, and the radiation dose was 11.7 +/- 7.1 mSv. The EVAR was
      an emergency in 64 patients. The mean screening time was 22.9 +/- 18.2 minutes,
      and the radiation dose was 13.4 +/- 8.6 mSv. During the first postoperative year,
      follow-up CT scans exposed the patients to 24.0 mSv, with 8.0 mSv in subsequent
      years. Abdominal radiographs added an additional 1.8 mSv each year. CONCLUSION:
      EVAR and the follow-up investigations involve substantial amounts of radiation,
      with well-recognized carcinogenic risks. Because patient safety is paramount,
      radiation exposure should be minimized. This may be possible by standardizing
      radiation exposure throughout the United Kingdom by implementing national
      guidelines and considering other imaging modalities for follow-up.

PMID- 20670774
TI  - Long-term follow-up of neck expansion after endovascular aortic aneurysm repair.
AB  - OBJECTIVE: This study determined the rate, extent, and clinical significance of
      neck dilatation after endovascular aneurysm repair (EVAR). METHODS: The study
      included 46 patients who underwent elective EVAR using bifurcated Zenith stent
      grafts (Cook, Bloomington, Ind) and had at least 48 months of clinical and
      radiographic follow-up. Computed tomography images were analyzed on a 3
      dimensional workstation (TeraRecon, San Mateo, Calif). Neck diameter was measured
      10 mm below the most inferior renal artery in planes orthogonal to the aorta.
      Nominal stent graft diameter was obtained from implantation records. RESULTS:
      Median follow-up was 59 months (range, 48-120 months). Neck dilation occurred in
      all 46 patients. The rate of neck dilation was greatest at early follow-up
      intervals. At 48 months, median neck dilation was 5.3 mm (range, 2.3-9.8 mm). The
      extent of neck dilation at 48 months correlated with percentage of stent graft
      oversizing (Spearman rho = 0.61, P < .001). No type I endoleak or migration >5 mm
      occurred. CONCLUSIONS: After EVAR with the Zenith stent graft, the neck dilates
      until its diameter approximates the diameter of the stent graft. Neck dilation
      was not associated with type I endoleak or migration of the stent graft.

PMID- 20670776
TI  - Evaluating parsimonious risk-adjustment models for comparing hospital outcomes
      with vascular surgery.
AB  - BACKGROUND: Most outcomes registries use a large number of variables to control
      for differences in patients. We sought to determine whether fewer variables could
      be used for risk adjustment without compromising hospital quality comparisons.
      METHODS: We used prospective, clinical data from the American College of Surgeons
      National Surgical Quality Improvement Program (ACS-NSQIP) for five commonly
      performed inpatient vascular procedures (N = 24,744). For each of the five
      operations, we compared the ability of two parsimonious models (an intermediate
      model, using the top five variables for each procedure and a limited model using
      the top 2 variables from each procedure) and the full model (up to 42 variables)
      to predict the risk of mortality and morbidity at the patient and hospital level.
      RESULTS: The parsimonious model was similar to the full model in all comparisons.
      For the five procedures, the intermediate, limited, and full models all had very
      similar discrimination at the patient-level (C indices of 0.87 vs 0.85 vs 0.87
      for mortality and 0.77 vs 0.75 vs 0.77 for morbidity), and similar calibration,
      as assessed with the Hosmer-Lemeshow test. In evaluating hospital-level morbidity
      and mortality rates, the correlations between the parsimonious and full models
      were very high for both mortality (>0.97 across operations) and morbidity (>0.97
      across operations). CONCLUSIONS: Hospital quality comparisons for vascular
      surgery can be adequately risk-adjusted using a small number of important
      variables. Reducing the number of variables collected will significantly decrease
      the burden of data collection for hospitals choosing to participate in the
      vascular module of the ACS-NSQIP.

PMID- 20670775
TI  - Abnormal joint powers before and after the onset of claudication symptoms.
AB  - OBJECTIVE: Claudication is the most common manifestation of peripheral arterial
      disease, producing significant ambulatory compromise. Our study evaluated
      patients with bilateral lower limb claudication and characterized their gait
      abnormality based on advanced biomechanical analysis using joint torques and
      powers. METHODS: Twenty patients with bilateral claudication (10 with isolated
      aortoiliac disease and 10 with combined aortoiliac and femoropopliteal disease)
      and 16 matched controls ambulated on a walkway while 3-dimensional biomechanical
      data were collected. Patients walked before and after onset of claudication pain.
      Joint torques and powers at early, mid, and late stance for the hip, knee, and
      ankle joints were calculated for claudicating patients before and after the onset
      of claudication pain and were compared to controls. RESULTS: Claudicating
      patients exhibited significantly reduced hip and knee power at early stance
      (weight-acceptance phase) due to decreased torques produced by the hip and knee
      extensors. In mid stance (single-limb support phase), patients had significantly
      reduced knee and hip power due to the decreased torques produced by the knee
      extensors and the hip flexors. In late stance (propulsion phase), reduced
      propulsion was noted with significant reduction in ankle plantar flexor torques
      and power. These differences were present before and after the onset of pain,
      with certain parameters worsening in association with pain. CONCLUSIONS: The gait
      of claudication is characterized by failure of specific and identifiable muscle
      groups needed to perform normal walking (weight acceptance, single-limb support,
      and propulsion). Parameters of gait are abnormal with the first steps taken, in
      the absence of pain, and certain of these parameters worsen after the onset of
      claudication pain.

PMID- 20670777
TI  - Extracorporeal shock wave therapy ameliorates secondary lymphedema by promoting
      lymphangiogenesis.
AB  - OBJECTIVE: Although secondary lymphedema is a common complication after surgical
      and radiation therapy for cancer, the treatment options for lymphedema remain
      limited and largely ineffective. We thus studied the effect of extracorporeal
      shock wave therapy on promoting lymphangiogenesis and improving secondary
      lymphedema. METHODS: A rabbit ear model of lymphedema was created by disruption
      of lymphatic vessels. Two weeks after surgery, the lymphedematous ear was treated
      with or without low-energy shock waves (0.09 mJ/mm(2), 200 shots), three times
      per week for 4 weeks. RESULTS: Western blot analysis showed that the expression
      of vascular endothelial growth factor (VEGF)-C (1.23-fold, P < .05) and VEGF
      receptor 3 (VEGFR3; 1.53-fold, P < .05) was significantly increased in the ears
      treated with shock wave than in the untreated lymphedematous ears. Compared with
      the control group, shock wave treatment led to a significant decrease in the
      thickness of lymphedematous ears (3.80 +/- 0.25 mm vs 4.54 +/- 0.18 mm, P < .05).
      Immunohistochemistry for VEGFR3 showed the density of lymphatic vessels was
      significantly increased by shock wave treatment (P < .05). CONCLUSION:
      Extracorporeal shock wave therapy promotes lymphangiogenesis and ameliorates
      secondary lymphedema, suggesting that extracorporeal shock wave therapy may be a
      novel, feasible, effective, and noninvasive treatment for lymphedema.

PMID- 20670778
TI  - Listeria monocytogenes as a rare cause of mycotic aortic aneurysm.
AB  - Mycotic aneurysms represent a diagnostic and therapeutic challenge still lacking
      general recommendations for optimal therapy. So far, Listeria monocytogenes (L.
      monocytogenes) is very rarely reported to be the causative organism of mycotic
      aortic aneurysms. We report 2 cases of mycotic abdominal aortic aneurysms due to
      L. monocytogenes infection being treated by radical debridement, open in situ
      reconstruction with aorto-bi-iliac Dacron grafts, and long-term antibiotic
      therapy. Both patients recovered well from surgery. Interestingly, the long-time
      follow-up for the first patient 9 years after surgery was entirely uneventful.
      Open debridement in an in situ reconstruction with Dacron grafts followed by
      antibiotic therapy seems to be a suitable therapeutic regime for mycotic
      aneurysms due to L. monocytogenes.

PMID- 20670779
TI  - Don't trust a vein graft to treat carotid aneurysm in patients with Behcet
      disease.
AB  - Extracranial carotid aneurysm is a rare vascular manifestation of Behcet disease.
      To our knowledge, only 32 cases have been reported. This article presents a
      complex case of a 28-year-old man who was first treated by vein graft
      reconstruction. At 12 months of follow-up, a nonanastomotic false aneurysm of the
      vein graft occurred and was treated by interposition of prosthetic graft. Two
      months later, an anastomotic pseudoaneurysm between the two grafts was excluded
      by two stent grafts. Based on our experience and a review of the literature, we
      compared the outcomes of prosthetic and autologous vein reconstructions and
      discussed the role of carotid ligation and immunosuppressive treatment.

PMID- 20670780
TI  - I know about Jack and you're no Jack Kevorkian.

PMID- 20670781
TI  - Asymptomatic carotid artery stenosis--medical therapy alone versus medical
      therapy plus carotid endarterectomy or stenting.
AB  - Vascular surgery has matured to the point that there exists robust bodies of
      literature exploring many of our therapies. However, this evidence is but one of
      the factors that dictate medical practice. Others include local patient
      demographics, the practical implications of healthcare delivery, and an
      individual surgeon's interpretation of this evidence, which can be somewhat
      subjective. As a result, there are numerous examples of vascular specialists'
      practice patterns differing depending on their geographic location. Recognizing
      this, the Editors of the Journal of Vascular Surgery and the European Journal of
      Vascular and Endovascular Surgery have developed a series of Trans-Atlantic
      Debates to explore these instances. The inaugural debate explores the
      controversial question of how best to manage asymptomatic carotid artery
      stenoses. Our debators, Peter Schneider and Ross Naylor, offer reasoned and
      passionate arguments to defend their differing approaches. We trust that this
      addition to our journals will prove enlightening and, perhaps, entertaining.

PMID- 20670782
TI  - Commentary.

PMID- 20670783
TI  - Halsted-Holman vascular trauma legacy.

PMID- 20670786
TI  - Regarding "A prospective open-label study of endovascular treatment of chronic
      cerebrospinal venous insufficiency".

PMID- 20670787
TI  - Regarding "Endovascular management of iliac rupture during endovascular aneurysm
      repair".

PMID- 20670788
TI  - A fellow's experience in Haiti.

PMID- 20670789
TI  - Regarding "High spatial resolution magnetic resonance imaging of cystic
      adventitial disease of the popliteal artery".

PMID- 20670791
TI  - Regarding "Serum carboxymethyllysine concentrations are reduced in diabetic men
      with abdominal aortic aneurysms: Health In Men Study".

PMID- 20670792
TI  - Regarding "Statins, heme oxygenase-1, iron, and atherosclerosis".

PMID- 20670795
TI  - Upper extremity technologic advances. Preface.

PMID- 20670796
TI  - The role of locking technology in the hand.
AB  - Locked fixed-angle plating in the hand and wrist helps to optimize outcomes
      following surgical fixation of select acute fractures and complex
      reconstructions. Select indications include unstable distal ulna head/neck
      fractures, periarticular metacarpal and phalangeal fractures,
      comminuted/multifragmentary diaphyseal fractures with bone loss (ie, combined
      injuries of the hand), osteopenic/pathologic fractures, nonunions and corrective
      osteotomy fixation, and small joint arthrodesis. Locked plating techniques in the
      hand should not be seen as a panacea for wrist and digital acute trauma and
      delayed reconstructions. An understanding of the biomechanics of fixed-angle
      plating and proper technical application of locking constructs will optimize
      outcomes and minimize complications. As clinical experience with locking
      technology in hand trauma broadens, new indications and applications will emerge.
      Currently, several systems are available. The specific implants share common
      features in their protocols for insertion, but unique differences in their design
      (ie, individual locking mechanisms, uniaxial vs polyaxial locking capability,
      metallurgy, and plate profiles) must be appreciated and considered
      preoperatively.

PMID- 20670797
TI  - Intramedullary nail fixation for metacarpal fractures.
AB  - Metacarpal fractures are common, especially in men, and account for about 10% of
      all fractures in patients. The fracture pattern and location, and the degree of
      angulation are important in determining the optimal treatment approach. Although
      metacarpal fractures can be treated nonsurgically, certain indications such as
      irreducible fractures, malrotations, and open fractures may necessitate surgery.
      Intramedullary nail fixation has been successful in treating metacarpal
      fractures. Complications can be minimized by taking appropriate precautions and
      care in performing the surgery.

PMID- 20670798
TI  - Implant arthroplasty of the carpometacarpal joint of the thumb.
AB  - Resection arthroplasty with or without ligament reconstruction for thumb
      trapeziometacarpal arthritis can be complicated by thumb shortening and pinch
      strength weakness. Implant arthroplasties have been developed to limit loss of
      thumb length, improve strength, and limit postoperative convalescence. The ideal
      thumb carpometacarpal implant should be strong and stable, provide full range of
      motion, and prevent loosening. Unfortunately, no current prosthesis accomplishes
      all of these goals. Until the ideal implant is developed, clinical acumen must be
      used to determine appropriate patients and implants.

PMID- 20670799
TI  - Interposition arthroplasty options for carpometacarpal arthritis of the thumb.
AB  - Carpometacarpal (CMC) arthritis of the thumb affects half of postmenopausal women
      and up to 25% of elderly men. This disease can cause significant disability in
      affected patients often necessitating surgical intervention. Various surgical
      options have been used to treat refractory CMC arthritis. Any successful surgical
      intervention must address three goals: removal of diseased joint surfaces,
      reconstruction of ligamentous stabilizers, and preservation of the joint space.
      In this article we will discuss various interposition arthroplasty options for
      CMC arthritis of the thumb.

PMID- 20670800
TI  - Headless compression screw fixation of scaphoid fractures.
AB  - Scaphoid fractures carry significant long-term morbidity and short-term
      socioeconomic difficulty in the young and active patient population in which they
      most commonly occur. While cast immobilization results in high rates of
      radiographic union in nondisplaced scaphoid fractures, internal fixation with
      headless compression screws has been recommended in cases of displaced fractures.
      Internal fixation has led to high rates of union in both nondisplaced and
      displaced fractures with the added benefits of earlier mobilization and return to
      work and sports. Multiple manufacturers are now offering "second generation"
      headless compression screws for the internal fixation of scaphoid fractures. The
      few biomechanical studies that exist demonstrate improved compression forces and
      load to failure for the newer generation of headless compression screws when
      compared with the first generation headless compression screw, although it is
      unclear if these differences are clinically significant.

PMID- 20670801
TI  - Intramedullary fixation of distal radius fractures.
AB  - Intramedullary fixation is the latest in a variety of techniques that have been
      developed to manage distal radius fractures. Intramedullary nailing of these
      fractures combines the soft-tissue advantages of a less invasive surgical
      approach with the biomechanical advantages of locking screw technology. These
      features may enable an accelerated postoperative rehabilitation and quicker
      return to function. Disadvantages associated with the intramedullary technique
      include the necessity of a closed or percutaneous reduction and the inability of
      the implant to adequately stabilize intraarticular or highly comminuted
      fractures. Consequently, intramedullary implants are primarily indicated for
      fixation of extra-articular or simple intraarticular split patterns and should
      not be employed for management of volar or dorsal shear fractures. Preliminary
      clinical data is emerging in the form of short-term follow-up studies with
      limited numbers of study participants.

PMID- 20670802
TI  - Variable-angle locking screw volar plating of distal radius fractures.
AB  - Surgical treatment options for distal radius fractures are many and commonly
      involve volar locked plating. More recently, newer volar locking plates have been
      introduced to the market that allow the placement of independent distal
      subchondral variable-angle locking screws to better achieve targeted fracture
      fixation. This article reviews this new technology and presents the authors'
      experience with the Aptus (Medartis, Kennett Square, Pennsylvania) variable-angle
      volar locking plates.

PMID- 20670803
TI  - Nonbridging external fixation of distal radius fractures.
AB  - Surgical management of distal radius fractures continues to evolve because of
      their high incidence in an increasingly active elderly population. Traditional
      radiocarpal external fixation relies on ligamentotaxis for fracture reduction but
      has several drawbacks. Nonbridging external fixation has evolved to provide early
      wrist mobility in the setting of anatomic fracture reduction. Several studies of
      the nonbridging technique have demonstrated satisfactory results in isolated
      nonbridging external fixation series and in comparison with traditional spanning
      external fixation. Nonbridging external fixation for surgical treatment of distal
      radius fractures can be technically demanding and requires at least 1 cm of
      intact volar cortex in the distal fracture fragment for successful
      implementation.

PMID- 20670804
TI  - Intramedullary fixation of forearm fractures.
AB  - Plate fixation remains the primary surgical treatment option for most adult
      forearm fractures. However, intramedullary nailing can be successful and might be
      preferable in cases of massive soft-tissue injury and burns, certain segmental
      fractures, pathologic fractures, and skeletally immature adolescent patients.
      Furthermore, the risk for refracture after plate removal is decreased with
      fixation by intramedullary nailing. The history, indications, surgical technique,
      and results of intramedullary fixation of forearm fractures are described in this
      article.

PMID- 20670805
TI  - Radial head arthroplasty.
AB  - Radial head arthroplasty remains an encouraging treatment option for comminuted
      radial head fractures in an unstable elbow or forearm. This article discusses the
      surgical considerations related to radial head arthroplasty, including anatomy,
      indications, and surgical technique. Radial head arthroplasty outcomes literature
      and a review of current implant options are also discussed.

PMID- 20670806
TI  - Use of orthogonal or parallel plating techniques to treat distal humerus
      fractures.
AB  - Distal humerus fractures continue to be a complex fracture to treat. This article
      describes two surgical techniques that can be used to tackle these difficult
      fractures: Parallel plating and orthogonal plating. Both techniques have yielded
      excellent outcomes after open reduction and internal fixation; yet each has its
      own set of unique considerations. However, the key to successful treatment of
      these difficult fractures regardless of technique remains obtaining anatomic
      reduction with stable fixation and the implementation of early motion.

PMID- 20670807
TI  - Hinged external fixation of the elbow.
AB  - Hinged external fixation of the elbow provides the advantages of static fixation
      with the benefits of continued motion through the joint. Indications for the use
      of this method of fixation include traumatic instability, distraction
      interposition arthroplasty, instability after contracture release, and
      instability after excision of heterotopic ossification. Orthopedic surgeons
      should be familiar with hinged fixators and their application when faced with an
      unstable ulnohumeral joint.

PMID- 20670808
TI  - The role of nerve allografts and conduits for nerve injuries.
AB  - Nerve repair after transection has variable and unpredictable outcomes. In
      addition to advancements in microvascular surgical techniques, nerve allografts
      and conduits are available options in peripheral nerve reconstruction. When
      tensionless nerve repair is not feasible, or in chronic injuries, autografts have
      been traditionally used. As substitute to autografts, decellularized allografts
      and conduits have become available. These conduits can reduce donor site
      morbidity, functional loss at the donor area in cases where autografts are used,
      and immune reaction from transplants or unprocessed allografts. The development
      of new biomaterials for use in conduits, as well as use of cytokines, growth
      factors, and other luminal fillers, may help in the treatment of acute and
      chronic nerve injuries. The indications and properties of nerve conduits and
      allografts are detailed in this article.

PMID- 20670809
TI  - Three-dimensional computed tomographic imaging and modeling in the upper
      extremity.
AB  - Technologic advances in imaging of the upper extremity have taken an immense leap
      in the last decade. So has the amount of research that has been published on this
      subject. Three-dimensional (3D) reconstructions, in particular, have improved
      identification of fracture characteristics, such as fragments, fracture edges,
      and articular surfaces. Three-dimensional physical models can even increase the
      advantages of the 3D reconstructions. Together, 3D reconstructions and physical
      modeling may outweigh the disadvantages of increased cost, resource usage, and
      additional time, as research has shown that it can benefit both the surgeon and
      the patient significantly.

PMID- 20670810
TI  - Foreword. Atopic dermatitis.

PMID- 20670811
TI  - Preface. Atopic dermatitis.

PMID- 20670812
TI  - Epidemiology of atopic dermatitis and atopic march in children.
AB  - Atopic dermatitis (AD) is one of the most common chronic childhood skin diseases
      affecting up to 17% of children in the United States. The point prevalence of AD
      has increased based on validated questionnaires in the most recent update of the
      International Study of Asthma and Allergies in Childhood. However, the increases
      are primarily in developing countries, whereas the rates have stabilized in
      countries with higher incomes. AD starts in early childhood with 65% of children
      affected by 18 months of age. Furthermore, less than half of the patients with AD
      have complete resolution by 7 years of age and only 60% have resolution by
      adulthood, indicating the chronic nature of AD. AD is a major risk factor for the
      development of asthma, with an increased odds ratio in children with AD in
      several longitudinal studies compared with children without AD, and about 30% of
      patients with AD develop asthma. Patients with atopic sensitization along with
      eczema are at a higher risk for progressing in the atopic march to asthma. The
      main risk factors for progression and persistence of asthma are early onset and
      severity of AD.

PMID- 20670813
TI  - Quality-of-life outcomes and measurement in childhood atopic dermatitis.
AB  - Atopic dermatitis is a common childhood skin disease of increasing prevalence
      that greatly affects the quality-of-life of affected children and their families.
      The complex and multidimensional effects of this disease have been described
      qualitatively and measured quantitatively with quality-of-life instruments. The
      burden of atopic dermatitis can likely be improved by identifying parents and
      their caregivers with impaired quality-of-life and providing appropriate
      education and psychosocial support.

PMID- 20670814
TI  - Allergic triggers in atopic dermatitis.
AB  - Food or environmental allergens play a significant pathogenic role in a subgroup
      of patients with atopic dermatitis (AD) and can trigger eczema flares. This
      review focuses on when and which diagnostic and allergen-avoidance measures are
      beneficial. Diagnosis of allergic triggers may be aided by skin-prick tests
      measuring serum-specific IgE and/or atopy patch tests (APT) based on the
      patient's history, and when necessary, oral food challenges (OFC). In a subset of
      patients, therapeutic measures, such as elimination of the incriminated
      allergen(s), can lead to marked improvement of AD; this is especially true for
      food allergens, but can also apply to inhalant allergens.

PMID- 20670816
TI  - Atopic dermatitis and keratoconjunctivitis.
AB  - Atopic dermatitis, a chronic disease seen by allergist-immunologists, has both
      dermatologic and ocular manifestations. The ocular component is often
      disproportionately higher than the dermatologic disease. Even if skin
      abnormalities seem well controlled, these patients require ophthalmic evaluation.
      Atopic keratoconjunctivitis in atopic dermatitis patients is characterized by
      acute exacerbations and requires maintenance therapy for long-term control.
      Future studies will continue to emphasize the use of steroid-sparing,
      immunomodulating agents that have the potential to provide long-lasting anti
      inflammatory control with a more favorable side-effect profile.

PMID- 20670815
TI  - The infectious aspects of atopic dermatitis.
AB  - Atopic dermatitis is characterized by Staphylococcus aureus colonization and
      recurrent skin infections. In addition to an increased risk of invasive
      infections by herpes simplex or vaccinia viruses, there is ample evidence that
      microbial pathogens, particularly S aureus and fungi, contribute to the cutaneous
      inflammation of atopic dermatitis. The authors describe recent developments in
      the pathogenesis of atopic dermatitis in relation to the role of microbial
      pathogens. Understanding how microbial pathogens interact or evade the cutaneous
      immunity of atopic dermatitis may be crucial in preventing infections or
      cutaneous inflammation in this disease.

PMID- 20670817
TI  - The role of contact allergy in atopic dermatitis.
AB  - Although allergic contact dermatitis (CD) was previously thought to occur less
      frequently in patients with atopic dermatitis (AD), more recent studies show that
      it is at least as common in patients with AD as in the general population, if not
      more so. Thus, patients with AD should be considered for patch testing (PT).
      Although conflicting data exist, the severity of the AD may impact the PT
      results. Furthermore, younger patients may yield more positive PT results. Hand
      eczema and compositae allergy are more common in atopic patients. Reassuringly,
      PT is positive for topical antiseptic and corticosteroids in only a small subset
      of patients. When personal products are patch tested, emollients should be
      included in the series.

PMID- 20670818
TI  - Evolution of conventional therapy in atopic dermatitis.
AB  - Conventional therapy for atopic dermatitis has evolved along with better
      understanding of underlying impaired barrier function, role of microorganisms,
      and immune abnormalities. Emollients, along with antimicrobial and topical anti
      inflammatory therapies, remain the cornerstone of conventional therapy. Recent
      therapeutic advances include use of nonsteroidal therapy for epidermal barrier
      repair, along with proactive therapy with topical corticosteroids and calcineurin
      inhibitors. Minimal anti-inflammatory treatment of the underlying residual
      disease is the immunobiologic rationale for proactive therapy. Further progress
      in understanding this increasingly common disease will hopefully lead to more
      targeted therapies.

PMID- 20670819
TI  - The role of the nurse educator in managing atopic dermatitis.
AB  - Nursing is making a key contribution to the development and evaluation of atopic
      dermatitis (AD) education. Educational interventions have long been recommended
      and used as a critical adjunct at all levels of therapy for patients with AD to
      enhance therapy effectiveness. These interventions may be directed toward adult
      patients or the parent/caregiver or child with eczema. Education should be
      individualized and includes teaching about the chronic or relapsing nature of AD,
      exacerbating factors, and therapeutic options with benefits, risks, and realistic
      expectations. This important educational facet of care management is becoming
      increasingly difficult to accomplish in routine care visits and seems to be
      equally difficult to measure and evaluate. A limited number of studies to date
      suggest effectiveness of educational approaches to improve the management of AD.
      We recommend that an international priority be given to assessing the effects of
      patient and parental education by nurses and other care providers in AD
      management using research studies designed to address the common weaknesses of
      existing randomized studies and the relative benefits of different strategies.

PMID- 20670820
TI  - Addressing psychosocial aspects of atopic dermatitis.
AB  - Moderate to severe atopic dermatitis (AD) negatively affects patients and their
      families. Pruritus, scratching, and sleep problems are common complaints linked
      to disturbed quality of life. Treatment is complex, and nonadherence rates are
      high. This article reviews the effect of AD on patients and their families and
      intervention strategies that have some success in improving quality of life. A
      treatment model for addressing the psychosocial effect of moderate to severe AD
      within a multidisciplinary setting is suggested herein.

PMID- 20670822
TI  - Complementary and alternative interventions in atopic dermatitis.
AB  - The burden of atopic diseases, including atopic dermatitis (AD), is significant
      and far-reaching. In addition to cost of care and therapies, it affects the
      quality of life for those affected as well as their caretakers. Complementary and
      alternative therapies are commonly used because of concerns about potential
      adverse effects of conventional therapies and frustration with the lack of
      response to prescribed medications, be it due to the severity of the AD or the
      lack of appropriate regular use. Despite the promising results reported with
      various herbal medicines and biologic products, the clinical efficacy of such
      alternative therapies remains to be determined. Physicians need to be educated
      about alternative therapies and discuss benefits and potential adverse effects or
      limitations with patients. A systematic approach and awareness of reputable and
      easily accessible resources are helpful in dealing with complementary and
      alternative medicine (CAM). The use of CAM interventions is common among
      individuals with AD. Epidemiologic data have been a motivating drive for better
      elucidation of the efficacy of CAM interventions for allergic disease. Herbal
      medicines and biologics for AD treatment and, more recently, prevention comprise
      a major area of clinical investigation. Potential mechanisms of therapeutic
      effect elucidated by animal models and human clinical studies implicate
      modulation of TH2-type allergic inflammation and induction of immune tolerance.
      Population-based research regarding the use of CAM for allergic diseases
      underscores the increasing challenge for care providers with respect to
      identifying CAM use and ensuring safe use of allopathic and complementary
      medicines in disease management.

PMID- 20670821
TI  - Vitamin D in atopic dermatitis, asthma and allergic diseases.
AB  - This review examines the scientific evidence behind the hypothesis that vitamin D
      plays a role in the pathogenesis of allergic diseases, along with a focus on
      emerging data regarding vitamin D and atopic dermatitis. Elucidated molecular
      interactions of vitamin D with components of the immune system and clinical data
      regarding vitamin D deficiency and atopic diseases are discussed. The rationale
      behind the sunshine hypothesis, laboratory evidence supporting links between
      vitamin D deficiency and allergic diseases, the clinical evidence for and against
      vitamin D playing a role in allergic diseases, and the emerging evidence
      regarding the potential use of vitamin D to augment the innate immune response in
      atopic dermatitis are reviewed.

PMID- 20670823
TI  - Investigational and unproven therapies in atopic dermatitis.
AB  - Atopic dermatitis can be a challenging disease to treat, often having a chronic
      or relapsing course. For patients with moderate to severe disease, it can result
      in significant morbidity and affect quality of life of patients or families.
      Current treatment can be associated with side effects or patient and caregiver
      concerns about use. Recent advances in the understanding of barrier defects and
      innate and adaptive immune systemic abnormalities in atopic dermatitis have
      provided potential new targets for therapeutic intervention. These advances
      include antimicrobial peptides, antistaphylococcal toxin strategies, Th2 cytokine
      inhibitors, and modulation of pruritus at the neuromediator level.

PMID- 20670824
TI  - Hunting-ton for new proteases: MMPs as the new target?
AB  - Mutant huntingtin proteolysis mediated by various proteases plays a key role in
      Huntington's disease (HD) pathogenesis. In this issue of Neuron, Miller et al.
      have identified 11 proteases, including matrix metalloproteinases (MMPs), that
      when inhibited reduce huntingtin proteolysis and produce beneficial therapeutic
      effects. These findings provide new insights into huntingtin proteolysis and its
      potential as a therapeutic target.

PMID- 20670825
TI  - Going tubular in the rostral migratory stream: neurons remodel astrocyte tubes to
      promote directional migration in the adult brain.
AB  - Newly generated neuroblasts from the subventricular zone of the adult brain
      migrate as neuronal chains within a network of astroglial tubes in the rostral
      migratory stream. This highly directed, rapid migration channels new neurons to
      the olfactory bulb. In this issue of Neuron, Kaneko et al. demonstrate that
      migrating neurons dynamically remodel the morphology and organization of
      astroglial tubes to promote long distance, directional migration of neurons in
      the adult brain.

PMID- 20670826
TI  - Pausing to regroup: thalamic gating of cortico-basal ganglia networks.
AB  - How the cholinergic and dopaminergic systems of the striatum interact and how
      these interface with the massive neocortical input to the striatum are classic
      questions of cardinal interest to neurology and psychiatry. In this issue of
      Neuron, Ding and colleagues show that a key to these puzzles lies in the thalamic
      inputs to the striatum targeting its cholinergic interneurons.

PMID- 20670827
TI  - The multisensory nature of unisensory cortices: a puzzle continued.
AB  - Multisensory integration is central to perception, and recent work drafts it as a
      distributed process involving many and even primary sensory cortices. Studies in
      behaving animals performing a multisensory task provide an ideal means to
      elucidate the underlying neural basis, and a new study by Lemus et al. in this
      issue of Neuron thrusts in this direction.

PMID- 20670828
TI  - The science of stroke: mechanisms in search of treatments.
AB  - This review focuses on mechanisms and emerging concepts that drive the science of
      stroke in a therapeutic direction. Once considered exclusively a disorder of
      blood vessels, growing evidence has led to the realization that the biological
      processes underlying stroke are driven by the interaction of neurons, glia,
      vascular cells, and matrix components, which actively participate in mechanisms
      of tissue injury and repair. As new targets are identified, new opportunities
      emerge that build on an appreciation of acute cellular events acting in a broader
      context of ongoing destructive, protective, and reparative processes. The burden
      of disease is great, and its magnitude widens as a role for blood vessels and
      stroke in vascular and nonvascular dementias becomes more clearly established.
      This review then poses a number of fundamental questions, the answers to which
      may generate new directions for research and possibly new treatments that could
      reduce the impact of this enormous economic and societal burden.

PMID- 20670829
TI  - Matrix metalloproteinases are modifiers of huntingtin proteolysis and toxicity in
      Huntington's disease.
AB  - Proteolytic cleavage of huntingtin (Htt) is known to be a key event in the
      pathogenesis of Huntington's disease (HD). Our understanding of proteolytic
      processing of Htt has thus far focused on the protease families-caspases and
      calpains. Identifying critical proteases involved in Htt proteolysis and toxicity
      using an unbiased approach has not been reported. To accomplish this, we designed
      a high-throughput western blot-based screen to examine the generation of the
      smallest N-terminal polyglutamine-containing Htt fragment. We screened 514 siRNAs
      targeting the repertoire of human protease genes. This screen identified 11
      proteases that, when inhibited, reduced Htt fragment accumulation. Three of these
      belonged to the matrix metalloproteinase (MMP) family. One family member, MMP-10,
      directly cleaves Htt and prevents cell death when knocked down in striatal
      Hdh(111Q/111Q) cells. Correspondingly, MMPs are activated in HD mouse models, and
      loss of function of Drosophila homologs of MMPs suppresses Htt-induced neuronal
      dysfunction in vivo.

PMID- 20670830
TI  - New neurons clear the path of astrocytic processes for their rapid migration in
      the adult brain.
AB  - In the long-range neuronal migration of adult mammals, young neurons travel from
      the subventricular zone to the olfactory bulb, a long journey (millimeters to
      centimeters, depending on the species). How can these neurons migrate through the
      dense meshwork of neuronal and glial processes of the adult brain parenchyma?
      Previous studies indicate that young neurons achieve this by migrating in chains
      through astrocytic tunnels. Here, we report that young migrating neurons actively
      control the formation and maintenance of their own migration route. New neurons
      secrete the diffusible protein Slit1, whose receptor, Robo, is expressed on
      astrocytes. We show that the Slit-Robo pathway is required for morphologic and
      organizational changes in astrocytes that result in the formation and maintenance
      of the astrocytic tunnels. Through this neuron-glia interaction, the new neurons
      regulate the formation of the astrocytic meshwork that is needed to enable their
      rapid and directional migration in adult brain.

PMID- 20670831
TI  - Modulation of high-voltage activated Ca(2+) channels by membrane
      phosphatidylinositol 4,5-bisphosphate.
AB  - Modulation of voltage-gated Ca(2+) channels controls activities of excitable
      cells. We show that high-voltage activated Ca(2+) channels are regulated by
      membrane phosphatidylinositol 4,5-bisphosphate (PIP(2)) with different
      sensitivities. Plasma membrane PIP(2) depletion by rapamycin-induced
      translocation of an inositol lipid 5-phosphatase or by a voltage-sensitive 5
      phosphatase (VSP) suppresses Ca(V)1.2 and Ca(V)1.3 channel currents by
      approximately 35% and Ca(V)2.1 and Ca(V)2.2 currents by 29% and 55%,
      respectively. Other Ca(V) channels are less sensitive. Inhibition is not relieved
      by strong depolarizing prepulses. It changes the voltage dependence of channel
      gating little. Recovery of currents from inhibition needs intracellular
      hydrolysable ATP, presumably for PIP(2) resynthesis. When PIP(2) is increased by
      overexpressing PIP 5-kinase, activation and inactivation of Ca(V)2.2 current slow
      and voltage-dependent gating shifts to slightly higher voltages. Thus, endogenous
      membrane PIP(2) supports high-voltage activated L-, N-, and P/Q-type Ca(2+)
      channels, and stimuli that activate phospholipase C deplete PIP(2) and reduce
      those Ca(2+) channel currents.

PMID- 20670832
TI  - CaMKII triggers the diffusional trapping of surface AMPARs through
      phosphorylation of stargazin.
AB  - The Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is critically required
      for the synaptic recruitment of AMPA-type glutamate receptors (AMPARs) during
      both development and plasticity. However, the underlying mechanism is unknown.
      Using single-particle tracking of AMPARs, we show that CaMKII activation and
      postsynaptic translocation induce the synaptic trapping of AMPARs diffusing in
      the membrane. AMPAR immobilization requires both phosphorylation of the auxiliary
      subunit Stargazin and its binding to PDZ domain scaffolds. It does not depend on
      the PDZ binding domain of GluA1 AMPAR subunit nor its phosphorylation at Ser831.
      Finally, CaMKII-dependent AMPAR immobilization regulates short-term plasticity.
      Thus, NMDA-dependent Ca(2+) influx in the post-synapse triggers a CaMKII- and
      Stargazin-dependent decrease in AMPAR diffusional exchange at synapses that
      controls synaptic function.

PMID- 20670833
TI  - Basal GABA regulates GABA(B)R conformation and release probability at single
      hippocampal synapses.
AB  - Presynaptic GABA(B) receptor (GABA(B)R) heterodimers are composed of GB(1a)/GB(2)
      subunits and critically influence synaptic and cognitive functions. Here, we
      explored local GABA(B)R activation by integrating optical tools for monitoring
      receptor conformation and synaptic vesicle release at individual presynaptic
      boutons of hippocampal neurons. Utilizing fluorescence resonance energy transfer
      (FRET) spectroscopy, we detected a wide range of FRET values for CFP/YFP-tagged
      GB(1a)/GB(2) receptors that negatively correlated with release probabilities at
      single synapses. High FRET of GABA(B)Rs associated with low release probability.
      Notably, pharmacological manipulations that either reduced or increased basal
      receptor activation decreased intersynapse variability of GB(1a)/GB(2) receptor
      conformation. Despite variability along axons, presynaptic GABA(B)R tone was
      dendrite specific, having a greater impact on synapses at highly innervated
      proximal branches. Prolonged neuronal inactivity reduced basal receptor
      activation, leading to homeostatic augmentation of release probability. Our
      findings suggest that local variations in basal GABA concentration are a major
      determinant of GB(1a)/GB(2) conformational variability, which contributes to
      heterogeneity of neurotransmitter release at hippocampal synapses.

PMID- 20670834
TI  - V-ATPase membrane sector associates with synaptobrevin to modulate
      neurotransmitter release.
AB  - Acidification of synaptic vesicles by the vacuolar proton ATPase is essential for
      loading with neurotransmitter. Debated findings have suggested that V-ATPase
      membrane domain (V0) also contributes to Ca(2+)-dependent transmitter release via
      a direct role in vesicle membrane fusion, but the underlying mechanisms remain
      obscure. We now report a direct interaction between V0 c-subunit and the v-SNARE
      synaptobrevin, constituting a molecular link between the V-ATPase and SNARE
      mediated fusion. Interaction domains were mapped to the membrane-proximal domain
      of VAMP2 and the cytosolic 3.4 loop of c-subunit. Acute perturbation of this
      interaction with c-subunit 3.4 loop peptides did not affect synaptic vesicle
      proton pump activity, but induced a substantial decrease in neurotransmitter
      release probability, inhibiting glutamatergic as well as cholinergic transmission
      in cortical slices and cultured sympathetic neurons, respectively. Thus, V-ATPase
      may ensure two independent functions: proton transport by a fully assembled V
      ATPase and a role in SNARE-dependent exocytosis by the V0 sector.

PMID- 20670835
TI  - NMDA receptor contributions to visual contrast coding.
AB  - In the retina, it is not well understood how visual processing depends on AMPA-
      and NMDA-type glutamate receptors. Here we investigated how these receptors
      contribute to contrast coding in identified guinea pig ganglion cell types in
      vitro. NMDA-mediated responses were negligible in ON alpha cells but substantial
      in OFF alpha and delta cells. OFF delta cell NMDA receptors were composed of
      GluN2B subunits. Using a novel deconvolution method, we determined the individual
      contributions of AMPA, NMDA, and inhibitory currents to light responses of each
      cell type. OFF alpha and delta cells used NMDA receptors for encoding either the
      full contrast range (alpha), including near-threshold responses, or only a high
      range (delta). However, contrast sensitivity depended substantially on NMDA
      receptors only in OFF alpha cells. NMDA receptors contribute to visual contrast
      coding in a cell-type-specific manner. Certain cell types generate excitatory
      responses using primarily AMPA receptors or disinhibition.

PMID- 20670836
TI  - Thalamic gating of corticostriatal signaling by cholinergic interneurons.
AB  - Salient stimuli redirect attention and suppress ongoing motor activity. This
      attentional shift is thought to rely upon thalamic signals to the striatum to
      shift cortically driven action selection, but the network mechanisms underlying
      this interaction are unclear. Using a brain slice preparation that preserved
      cortico- and thalamostriatal connectivity, it was found that activation of
      thalamostriatal axons in a way that mimicked the response to salient stimuli
      induced a burst of spikes in striatal cholinergic interneurons that was followed
      by a pause lasting more than half a second. This patterned interneuron activity
      triggered a transient, presynaptic suppression of cortical input to both major
      classes of principal medium spiny neuron (MSN) that gave way to a prolonged
      enhancement of postsynaptic responsiveness in striatopallidal MSNs controlling
      motor suppression. This differential regulation of the corticostriatal circuitry
      provides a neural substrate for attentional shifts and cessation of ongoing motor
      activity with the appearance of salient environmental stimuli.

PMID- 20670837
TI  - Oscillations and filtering networks support flexible routing of information.
AB  - The mammalian brain exhibits profuse interregional connectivity. How information
      flow is rapidly and flexibly switched among connected areas remains poorly
      understood. Task-dependent changes in the power and interregion coherence of
      network oscillations suggest that such oscillations play a role in signal
      routing. We show that switching one of several convergent pathways from an
      asynchronous to an oscillatory state allows accurate selective transmission of
      population-coded information, which can be extracted even when other convergent
      pathways fire asynchronously at comparable rates. We further show that the band
      pass filtering required to perform this information extraction can be implemented
      in a simple spiking network model with a single feed-forward interneuron layer.
      This constitutes a mechanism for flexible signal routing in neural circuits,
      which exploits sparsely synchronized network oscillations and temporal filtering
      by feed-forward inhibition.

PMID- 20670838
TI  - Activity-dependent expression of Lmx1b regulates specification of serotonergic
      neurons modulating swimming behavior.
AB  - Genetic programs, environmental factors, and electrical activity interact to
      drive the maturation of the brain. Although the cascade of transcription factors
      that leads to specification of the serotonergic phenotype has been well
      characterized, its interactions with electrical activity are not known. Here we
      show that spontaneous calcium spike activity in the hindbrain of developing
      Xenopus laevis larvae modulates the specification of serotonergic neurons via
      regulation of expression of the Lmx1b transcription factor. Activity acts
      downstream of Nkx2.2 but upstream of Lmx1b, leading to regulation of the
      serotonergic phenotype. Using global manipulation of activity and targeted
      alteration of Lmx1b expression, we also demonstrate that changes in the number of
      serotonergic neurons change larval swimming behavior. The results link activity
      dependent regulation of a transcription factor to transmitter specification and
      altered behavior.

PMID- 20670839
TI  - Do sensory cortices process more than one sensory modality during perceptual
      judgments?
AB  - Recent studies have reported that sensory cortices process more than one sensory
      modality, challenging the long-lasting concept that they process only one.
      However, both the identity of these multimodal responses and whether they
      contribute to perceptual judgments is unclear. We recorded from single neurons in
      somatosensory cortices and primary auditory cortex while trained monkeys
      discriminated, on interleaved trials, either between two tactile flutter stimuli
      or between two acoustic flutter stimuli, and during discrimination sets that
      combined these two sensory modalities. We found neurons in these sensory cortices
      that responded to stimuli that are not of their principal sensory modality during
      these tasks. However, the identity of the stimulus could only be decoded from
      responses to their principal sensory modality during the stimulation periods and
      not during the processing steps that link sensation and decision making. These
      results suggest that multimodal encoding and perceptual judgments in these tasks
      occur outside the sensory cortices studied here.

PMID- 20670840
TI  - Plasma corin levels provide minimal prognostic utility incremental to natriuretic
      peptides in chronic systolic heart failure.
AB  - BACKGROUND: Corin is a serine protease that cleaves pro-atrial and pro-B-type
      natriuretic peptides into biologically active hormones. The relationship between
      soluble plasma corin levels, plasma natriuretic peptide levels, myocardial
      structure and performance, and long-term clinical outcomes in the setting of
      chronic systolic heart failure has not been described. METHODS AND RESULTS: In
      126 patients with chronic systolic heart failure (left ventricular ejection
      fraction <or=35%, New York Heart Association functional Class I-IV), we measured
      plasma corin and natriuretic peptide levels and performed comprehensive
      echocardiography with assessment of cardiac structure and performance. Adverse
      clinical events (all-cause mortality, cardiac transplantation, or heart failure
      hospitalization) were prospectively tracked for a median of 38 months. Plasma
      corin levels modestly correlated with echocardiographic indices of cardiac
      structure, including left ventricular mass index (r = 0.30, P = .003) and
      interventricular septum width (r = 0.22, P = .013). However, plasma corin levels
      did not correlate with age, arterial pressures, estimated glomerular filtration
      rate, echocardiographic indices of systolic or diastolic function, or plasma
      natriuretic peptide levels. In Cox proportional hazards analysis, higher plasma
      corin levels did not predict reduced risk of adverse clinical events (hazard
      ratio 0.91; 95% confidence interval 0.67-1.24, P = .52), and did not provide
      incremental prognostic value to natriuretic peptide levels. CONCLUSION: In our
      cohort of ambulatory patients with chronic systolic heart failure, soluble plasma
      corin levels did not provide prognostic utility incremental to that of
      natriuretic peptides.

PMID- 20670841
TI  - Differential changes in TGF-beta/BMP signaling pathway in the right ventricular
      myocardium of newborns with hypoplastic left heart syndrome.
AB  - BACKGROUND: Hypoplastic left heart syndrome (HLHS) is characterized by
      underdevelopment of the left ventricle (LV) and increased biomechanical stress on
      the right ventricle (RV) from single ventricle physiology. Despite the clinical
      significance, the signaling pathways active during RV remodeling and disease
      progression are not known. To address this, we examined differential changes in
      expression of genes associated with transforming growth factor-beta (TGF
      beta)/bone morphogenetic protein (BMP) signaling in RV tissue isolated from HLHS
      patients relative to RV and LV tissue from control subjects. METHODS AND RESULTS:
      Quantitative real-time polymerase chain reaction was used to detect changes in
      expression of 84 genes involved in TGF-beta/BMP-mediated cardiac development,
      cell growth, and differentiation in RV tissue collected from 6 neonates with HLHS
      undergoing stage 1 Norwood procedure (age, 1-7 days; mean, 4 days) and RV and LV
      tissue obtained from 5 infants with noncardiac pathology (age range, 1-135 days:
      mean, 85 days) that served as controls. Analysis of gene expression profiles
      between control-LV and control-RV revealed significant depression of TGF-beta/BMP
      signaling in RV compared with LV. Of the 84 genes analyzed, 38 were
      differentially expressed between HLHS-RV and control-RV, whereas only 22 compared
      with control-LV. Significant changes were observed in: tissue remodeling genes
      including Activin receptor type IIA (ACVR2A) (+2.13) and Activin receptor-like
      kinase 1 (ACVRL1) (+2.22); and cell survival, growth, and differentiation genes
      including CDC25A (+2.18), p21 (-3.64), p15 (+2.15), BMP5 (+4.58), BMP3 (+2.16),
      GDF3 (+8.59), NODAL (+2.32), and BMP binding endothelial regulator (BMPER)
      (+4.58). The most significant changes common to HLHS-RV versus control-RV and
      control-LV sample groups is observed for Anti mullerian hormone receptor 2
      (AMHR2) (+18.79 control-RV, +3.38 control-LV), and the BMP antagonist Inhibin
      alpha (INHA) (+11.47 control-RV, +5.73 control-LV). CONCLUSIONS: Although this
      descriptive study does not allow cause-effect inferences, our results suggest
      changes in cardiac development pathways and upregulation of genes associated with
      cell growth and differentiation in the neonatal RV of children with HLHS. These
      molecular profiles are more closely related to those observed in the normal LV
      rather than normal RV at similar maturational age. This work provides the basis
      for future mechanistic studies to elucidate the molecular mechanisms regulating
      RV remodeling in HLHS.

PMID- 20670842
TI  - Clinical significance of endogenous vasoactive neurohormones in chronic systolic
      heart failure.
AB  - BACKGROUND: Neurohormonal activation is a pathophysiological hallmark of acute
      and chronic heart failure (HF). The clinical significance of more recently
      discovered endogenous vasoactive hormones has not been well-characterized.
      METHODS AND RESULTS: In 154 subjects with stable, chronic systolic HF (New York
      Heart Association Class I-IV, left ventricular [LV] ejection fraction <or=40%),
      we measured plasma levels of urocortin 1 (UCN-1), urotensin II (UT-II), and
      endothelin-1 (ET-1) and performed comprehensive echocardiography with assessment
      of cardiac structure and performance. Adverse clinical events (all-cause
      mortality, cardiac transplantation or HF hospitalization) were prospectively
      tracked for a median of 39 months. Plasma levels of UCN-1 and ET-1 (but not UT
      II) increased with LV diastolic dysfunction stage, right ventricular systolic
      dysfunction class, and mitral regurgitation severity (P < .01 for all). Higher
      plasma levels of UCN-1 and ET-1 (but not UT-II) predicted increased risk for
      adverse clinical events. After adjustment for age, LV ejection fraction, and
      plasma amino-terminal pro-B-type natriuretic peptide, plasma UCN-1 >or=12.1 pM
      (HR: 2.02, 95% CI: 1.08-3.93, P = .029) and ET-1 >or=2.29 pM (HR: 2.52, 95% CI:
      1.24-5.03, P = .011) remained significant independent risk factors for adverse
      clinical events. CONCLUSION: Higher levels of plasma levels of UCN-1 and ET-1 but
      not UT-II were associated with worse LV diastolic performance and poorer long
      term clinical outcomes in patients with chronic systolic HF.

PMID- 20670843
TI  - Comparison of global and regional abnormalities in 99mTc-sestamibi and cardiac
      magnetic resonance imaging in dilated cardiomyopathy.
AB  - OBJECTIVE: The clinical relevance of perfusion defects and increased washout rate
      (WOR) in (99m)Tc-sestamibi (Tc MIBI) imaging has not been well characterized in
      dilated cardiomyopathy (DCM). We analyzed abnormalities in Tc MIBI imaging in
      relation to those in cardiac magnetic resonance (CMR) imaging. METHODS AND
      RESULTS: Nineteen DCM patients underwent both Tc MIBI and CMR imaging. The
      perfusion defects and global and regional MIBI WORs were evaluated with planar
      and single photon emission computed tomography (SPECT) images. The left
      ventricular function and the delayed enhancement (DE) were estimated with the
      cine- and DE-mode CMR. In the DCM patients, the Tc MIBI SPECT showed perfusion
      defects in 65 segments of 14 patients. The global and regional Tc MIBI WORs were
      higher than those in 10 normal volunteers (19.4 +/- 9.1% vs. 11.7 +/- 6.8% in
      global and 13.8 +/- 8.6% vs. 9.6 +/- 8.2% in regional WORs; mean +/- SD, P <
      .01). The DE-mode CMR demonstrated DE in 103 segments of 14 patients. The
      severity of perfusion defects was correlated with the extent of DE (r = 0.71, P <
      .01). The regional Tc MIBI WOR was highest in the segments with perfusion defects
      or DE, but the Tc MIBI WOR in segments without them was also higher than that in
      the normal volunteers. There was a weak but significant negative correlation
      between the regional Tc MIBI WOR and wall thickening (r = -0.23, P < .01).
      CONCLUSIONS: In DCM, the severity of perfusion defects and the increase in Tc
      MIBI WOR reflect the spread of myocardial fibrosis and/or scar. The increase in
      Tc MIBI WOR is potentially associated with regional dysfunction of LV wall.

PMID- 20670844
TI  - Correcting anemia in heart failure: the efficacy and safety of erythropoiesis
      stimulating agents.
AB  - BACKGROUND: Randomized controlled trials (RCTs) evaluating the efficacy and
      safety of erythropoiesis-stimulating agents (ESAs), including erythropoietin and
      darbepoetin, among patients with chronic heart failure (CHF) and anemia have
      yielded heterogeneous results, and important safety questions remain unanswered.
      We therefore undertook a meta-analysis to examine the effects of ESAs in this
      population. METHODS AND RESULTS: We systematically searched EMBASE, Medline, the
      Cochrane Library, ClinicalTrials.gov, and relevant bibliographies to identify all
      relevant RCTs. Data were aggregated using random-effects models. We identified 9
      RCTs (n = 747 patients). Compared with control, ESAs were associated with a
      significant reduction in CHF-related hospitalizations (odds ratio [OR] = 0.41;
      95% confidence interval [CI] = 0.24-0.69). The effect of ESAs on mortality was
      inconclusive (OR = 0.60; 95% CI = 0.32-1.11). ESAs were associated with improved
      quality of life and left ventricular ejection fraction, lower brain-natriuretic
      peptide levels, and improved exercise tolerance test performance. There was no
      evidence of an increase in the incidence of adverse events among patients
      randomized to ESAs (OR = 0.86; 95% CI = 0.51-1.42). CONCLUSIONS: In patients with
      CHF and anemia, ESAs are associated with a decrease in CHF-related
      hospitalizations and improved quality of life and exercise tolerance. However,
      RCTs completed to date have involved a small number of patients, and available
      mortality data are inconclusive.

PMID- 20670845
TI  - Development and validation of a computer adaptive test for measuring dyspnea in
      heart failure.
AB  - BACKGROUND: Dyspnea is a common symptom among patients with heart failure.
      Currently, there is no standardized, rapid, precise method to assess dyspnea.
      METHODS AND RESULTS: From a review of the literature, we pooled questions from
      various questionnaires assessing dyspnea. A total of 201 patients with heart
      failure completed all questions in the preliminary item bank. Each item asks how
      much shortness of breath the patient had when doing an activity. Medical charts
      were reviewed for hospitalization within 1 or 3 months of completing the
      questions. We created a dyspnea item bank of 44 items. Computer adaptive tests
      (CAT) generated from this item bank can assess dyspnea by administering on
      average 10 questions. Simulation CAT scores were generated to compare with the
      item bank scores. The CAT scores had a correlation of 0.98 with item bank scores.
      Logistic regression models predicting the probability of being hospitalized from
      the dyspnea score were statistically significant (P < .05). A 5-point score
      increase was associated with a 32% increased odds of hospitalization in 1 month
      and a 20% increased odds of hospitalization in 3 months. CONCLUSIONS: This
      computer-based tool for dyspnea assessment obtains similar precision to that of
      answering the entire dyspnea item bank with less patient burden.

PMID- 20670846
TI  - Cytokine combination therapy with long-acting erythropoietin and granulocyte
      colony stimulating factor improves cardiac function but is not superior than
      monotherapy in a mouse model of acute myocardial infarction.
AB  - BACKGROUND: Erythropoietin (EPO) and granulocyte colony stimulating factor (GCSF)
      are potential novel therapies after myocardial infarction (MI). We first
      established the optimal and clinically applicable dosages of these drugs in
      mobilizing hematopoietic stem cells (HSC), and then tested the efficacy of
      monotherapy and combination therapy post-MI. METHODS AND RESULTS: Optimal doses
      were established in enhanced green fluorescent protein (eGFP) + chimeric mice (n
      = 30). Next, mice underwent MI and randomized into 4 groups (n = 18/group): 1)
      GCSF; 2) EPO; 3) EPO+GCSF; and 4) control. Left ventricular (LV) function was
      analyzed pre-MI, at 4 hours and at 28 days post-MI. Histological assessment of
      infarct size, blood vessels, apoptotic cardiomyocytes, and engraftment of eGFP+
      mobilized cells were analyzed at day 28. LV function in the control group
      continued to deteriorate, whereas all treatments showed stabilization. The
      treatment groups resulted in less scarring, increased numbers of mobilized cells
      to the infarct border zone (BZ), and a reduction in the number of apoptotic
      cardiomyocytes. Both EPO groups had significantly more capillaries and arterioles
      at the BZ. CONCLUSION: We have established the optimal doses for EPO and GCSF in
      mobilizing HSC from the bone marrow and demonstrated that therapy with these
      agents, either as monotherapy or combination therapy, led to improvement of
      cardiac function post-MI. Combination therapy does not seem to have additive
      benefit over monotherapy in this model.

PMID- 20670847
TI  - Beneficial effects of atorvastatin on lung structural remodeling and function in
      ischemic heart failure.
AB  - BACKGROUND: Studies have suggested some benefit of 3-hydroxy-3-methyl-glutaryl
      CoA reductase inhibitors in congestive heart failure (CHF), although the
      mechanisms remain uncertain. We hypothesized that statins could improve pulmonary
      hypertension and right ventricular function in ischemic CHF by reducing lung
      remodeling. METHODS AND RESULTS: Two weeks after myocardial infarct, rats
      received atorvastatin (n = 23) or no treatment (n = 23) for 3 weeks and were
      compared with a sham group (n = 16). Infarct size was similar by echocardiography
      and pathologic evaluations. Atorvastatin greatly reduced pulmonary hypertension
      and right ventricular hypertrophy: right ventricular systolic pressure 42 +/- 5
      vs. 28 +/- 2 mm Hg (P < .01). Atorvastatin did not reduce left ventricular
      fibrosis and had minimal effects on left ventricular function. Right ventricular
      myocardial performance index was markedly improved by therapy (P < .01). CHF
      caused a restrictive lung syndrome with a downward shift of the respiratory
      pressure-volume loop, increased dry lung weight, and interstitial fibrosis that
      were greatly improved by atorvastatin. Reduced lung nitric oxide synthase
      expression was normalized by treatment. Atorvastatin also reduced isolated lung
      myofibroblasts proliferation after transforming growth factor-beta stimulation (
      36 +/- 6%, P < 0.01). CONCLUSIONS: 3-hydroxy-3-methyl-glutaryl-CoA reductase
      inhibition reduces lung remodeling and dysfunction associated with heart failure
      with prevention of right ventricular hypertrophy and pulmonary hypertension.

PMID- 20670848
TI  - Early short-term vagal nerve stimulation attenuates cardiac remodeling after
      reperfused myocardial infarction.
AB  - BACKGROUND: Vagal nerve stimulation (VS) has been suggested to be an effective
      adjunct to reperfusion therapy in myocardial infarction (MI). However, the effect
      of VS on left ventricular (LV) remodeling after reperfused MI has not been
      examined. METHODS AND RESULTS: We investigated the effects of early, brief VS on
      acute inflammatory reactions (study 1) and chronic LV remodeling (study 2) in a
      rabbit model of reperfused MI. In study 1, rabbits were subjected to 60-minute
      coronary artery occlusion followed by reperfusion alone (MI, n = 8) or treated
      with 24-hour VS (MI-VS, n = 8). At 24 hours after ischemia-reperfusion, MI-VS
      rabbits showed significantly decreased myocardial infiltration of neutrophils and
      reduced myocardial expressions of tumor necrosis factor-alpha and matrix
      metalloproteinase-8 and -9, compared with MI rabbits. Myocardial expression of
      interleukin-6 was not affected by VS. In study 2, rabbits were subjected to
      coronary occlusion and reperfusion alone (n = 16) or treated with VS for 3 days
      (n = 14). At 8 weeks after ischemia-reperfusion, MI-VS rabbits showed
      significantly improved LV dysfunction and dilatation, and significantly reduced
      infarct size, infarct wall thinning, and LV weight compared with MI rabbits.
      CONCLUSION: Early, short-term VS attenuates LV remodeling after reperfused MI,
      which may be associated with suppression of acute inflammatory reactions.

PMID- 20670849
TI  - Spatial heterogeneity of protein expression induced by dyssynchronous right
      ventricular pacing in the left ventricle of dogs with preserved systolic
      function.
AB  - BACKGROUND: Right ventricular (RV) apical pacing may result in ventricular
      dyssynchrony, which is associated with functional and morphological changes in
      the left ventricle (LV). Our aim is to assess contraction and hypertrophy-related
      protein expression changes in the LV after RV apical pacing. METHODS AND RESULTS:
      Six dogs underwent dual chamber pacemaker (DDD) implantation and atrioventricular
      nodal catheter ablation. The pacing group received atria-sensed RV apical pacing
      for 12 weeks. LV dyssynchrony was assessed with speckle tracking technique.
      Subsequently, hearts were processed for Western blotting. Four sham-operated dogs
      were included for comparison. After 12 weeks of RV pacing, cardiac chamber size
      and LV ejection fraction remained unchanged. Both electrical and mechanical
      dyssynchrony were evident in RV-paced dogs compared with sham-operated dogs. The
      late-activated LV lateral wall of paced dogs displayed a 23% reduction in the
      amount of sarcoplasmic reticulum Ca(2+) ATPase, a 32% reduction in phospholamban
      levels, but a 3.6-fold increase in phospho-JNK expression, a 2.2-fold increase in
      phospho-p38, and 1.9-fold increase in phospho-ERK expression. There were no
      significant differences in the early-activated LV septum between paced and sham
      dogs. CONCLUSIONS: Temporal dispersion of mechanical activation by RV apical
      pacing induced spatial dispersion of protein expression in the LV.

PMID- 20670851
TI  - Subjective versus objective classification of NYHA class IV.

PMID- 20670852
TI  - Iliosacral screw fixation of transforaminal sacral fractures using local
      anesthesia and CT.

PMID- 20670853
TI  - Wherever the dart lands: toward the ideal trauma system.

PMID- 20670854
TI  - Reduced incidence of gestational diabetes with bariatric surgery.
AB  - BACKGROUND: Obesity is a risk factor for gestational diabetes mellitus (GDM), and
      bariatric surgery is an effective treatment for obesity. Our objective was to
      determine the association of bariatric surgery with the incidence of GDM and
      related complications. STUDY DESIGN: We performed a retrospective study comparing
      rates of GDM and related outcomes (including cesarean section, large-for
      gestational-age infant, shoulder dystocia, and infection) between a group of
      women with a delivery before bariatric surgery and a group with a delivery after
      bariatric surgery. We used a private insurance claims database with information
      on 23,594 women who had bariatric surgery between 2002 and 2006. The dataset was
      searched to identify women with codes for bariatric surgery and a pregnancy
      resulting in a delivery at greater than 22 weeks gestation. Incidences of GDM and
      selected delivery complications for delivery before versus after bariatric
      surgery were compared using Fisher exact test and logistic regression. RESULTS:
      There were 346 women who had a delivery before bariatric surgery, and 354 had a
      delivery after bariatric surgery. Women with delivery after bariatric surgery had
      lower incidences of GDM (8% vs 27%, odds ratio (OR) 0.23, (95% CI 0.15 to 0.36)
      and cesarean section (28% vs 43%, OR0.53, 95% CI 0.39 to 0.72) than those with
      delivery before bariatric surgery. CONCLUSIONS: Bariatric surgery is associated
      with a decreased incidence of GDM and cesarean section in subsequent pregnancies.
      This potential effect of bariatric surgery should be considered in the management
      of obese women of childbearing age. Prospective studies are needed to confirm
      these findings.

PMID- 20670855
TI  - A current profile and assessment of north american cholecystectomy: results from
      the american college of surgeons national surgical quality improvement program.
AB  - BACKGROUND: Cholecystectomy is among the most common surgical procedures
      performed in the United States. The current state of cholecystectomy outcomes,
      including variations in hospital performance, is unclear. The objective of this
      study is to compare the risk factors, indications, and 30-day outcomes, as well
      as variations in hospital performance associated with laparoscopic (LC) versus
      open cholecystectomy (OC) at 221 hospitals during a 4-year period. STUDY DESIGN:
      Using the American College of Surgeons National Surgical Quality Improvement
      Program (ACS NSQIP) database (2005-2008), patients were identified who underwent
      cholecystectomy and related procedures (cholangiogram and/or common bile duct
      exploration). Four outcomes were studied, ie, 30-day overall morbidity, serious
      morbidity, surgical site infections, and mortality. Forward stepwise logistic
      regressions yielded patient-level predicted probabilities, and hospital-level
      observed-to-expected ratios were determined. RESULTS: Of 65,511 patients, 58,659
      (89.5%) underwent LC; 6,852 (10.5%) underwent OC. OC patients were considerably
      older with a higher comorbidity burden. LC patients were less likely to
      experience any morbidity (3.1% versus 17.8%; p < 0.0001), a serious morbidity
      (1.4% versus 11.1%; p < 0.0001), or a surgical site infection (1.3% versus 8.4%;
      p < 0.0001), and less likely to die (0.3% versus 2.8%; p < 0.0001). Observed-to
      expected ratios for overall morbidity ranged from 0 to 3.55; for serious
      morbidity, 0 to 3.23; for surgical site infection, 0 to 7.02; for mortality, 0 to
      13.05. CONCLUSIONS: Although overall incidence of adverse events is low after LC,
      substantial morbidity and mortality are associated with OC. Additionally,
      controlling for patient- and operation-related factors, considerable variations
      exist in hospital performance when evaluating 30-day outcomes after
      cholecystectomy.

PMID- 20670856
TI  - Gene signature is associated with early stage rectal cancer recurrence.
AB  - BACKGROUND: Despite expected excellent outcomes of surgical resection for early
      stage rectal cancers, 20% of stage I and II rectal cancers recur. Identifying
      biologic factors that predict the subset prone to recur could allow more directed
      therapy. This study identifies a tumor gene expression profile that accurately
      predicts disease recurrence. STUDY DESIGN: Stage I/II rectal cancer patients
      treated by surgery alone at a single institution were included and classified as
      having recurrent or nonrecurrent cancer. Tumor mRNA was isolated from frozen
      tissue and evaluated for total genome gene expression by microarray analysis.
      Background-corrected and normalized microarray data were analyzed using BAMarray
      software. Selected genes were further analyzed using unsupervised clustering and
      nearest-centroid classification. A balanced K-fold scoring-pair algorithm using
      1,000 independent replications was used for gene signature development. RESULTS:
      Sixty-nine patients with disease-free survival and 31 patients with recurrent
      disease were included at a median follow-up of 105 months (interquartile range
      114 months) and 32 months (interquartile range 25 months), respectively.
      Demographics and tumor characteristics between groups were similar. Fifty-two
      genes from 43,148 probes were differentially expressed, and a 36-gene signature
      was found to be statistically associated with recurrence using a scoring-pair
      algorithm. Accuracy to identify recurrence as measured by area under the receiver
      operating characteristic curve was 0.803. CONCLUSIONS: Differential gene
      expression within rectal cancers is associated with recurrence of early stage
      disease. A 36-gene signature correlates with an increased risk of more or less
      aggressive tumor behavior. This information obtainable at biopsy may assist in
      determining treatment decisions.

PMID- 20670857
TI  - Number of metastatic lymph nodes, but not lymph node ratio, is an independent
      prognostic factor after resection of pancreatic carcinoma.
AB  - BACKGROUND: This study evaluated the prognostic significance of the number of
      metastatic lymph nodes and the ratio of metastatic nodes to total number of
      examined lymph nodes (lymph node ratio, LNR) after resection of pancreatic
      carcinoma. STUDY DESIGN: Records of 119 consecutive patients with pancreatic
      ductal carcinoma, who underwent R0 or R1 pancreatectomy with regional node
      dissection, were reviewed retrospectively. Clinical factors, pathologic factors
      including number of metastatic nodes and LNR, and survival were analyzed by
      univariate and multivariate analyses. RESULTS: Overall survival rates were 78%,
      28%, and 20% at 1, 3, and 5 years, respectively. The median numbers of evaluated
      lymph nodes and involved nodes were 28 and 3, respectively. Univariate analysis
      revealed that tumor location, postoperative adjuvant chemotherapy, tumor
      differentiation, choledochal invasion, portal or splenic vein invasion,
      extrapancreatic nerve plexus invasion, resection margin status, node status,
      number of involved nodes, LNR, International Union against Cancer (UICC) pT
      factor, and UICC stage correlated significantly (p < 0.05) with increased
      survival. By multivariate analysis, negative node metastasis (p = 0.008) and 0 or
      1 involved node (p = 0.004), but not LNR, correlated independently with longer
      survival. The 1-, 3-, and 5-year survival rates of patients with 0 or 1
      metastatic node and patients with 2 or more metastatic nodes were 91%, 48%, and
      40% and 66%, 10%, and 0%, respectively. CONCLUSIONS: The number of metastatic
      nodes, but not LNR, is one of the most powerful prognostic factors after
      resection of pancreatic carcinoma.

PMID- 20670858
TI  - Multidisciplinary management strategy for incidental cystic lesions of the
      pancreas.
AB  - BACKGROUND: At our institution, incidental pancreatic cysts are frequently
      identified in asymptomatic patients undergoing routine imaging for staging of
      nonpancreatic malignancies. Management of these patients is unclear because a
      small but significant number of incidental pancreatic cysts are malignant. STUDY
      DESIGN: Our institutional database was reviewed for patients with ICD-9 codes for
      pancreatic cysts from 1980 to 2005. Clinicopathologic factors, including CT and
      endoscopic ultrasound (EUS) characteristics and management strategies, were
      analyzed. RESULTS: Over 25 years, 942 patients were identified with pancreatic
      cysts. Excluding those with symptoms or pseudocysts, 350 patients remained with
      incidental pancreatic cysts. Mean overall survival was 41.4 months (mean follow
      up 32.7 months). Forty-one patients underwent resection, of whom 38 (92.7%) had
      premalignant or malignant pathology. Univariate analysis of variables predicting
      pathologic premalignant or malignant diagnosis identified pancreatic neck or body
      location as significant factors. CONCLUSIONS: These data suggest that most
      incidental pancreatic cysts can be managed nonoperatively using a selective
      strategy based on detailed review of CT imaging and EUS findings.

PMID- 20670859
TI  - A population-based analysis of neighborhood socioeconomic status and injury
      admission rates and in-hospital mortality.
AB  - BACKGROUND: Research indicates that neighborhood socioeconomic status (N-SES) is
      inversely related to injury and injury-related mortality. We hypothesized that
      injury-related hospitalization rates would vary by N-SES and that N-SES would be
      related to in-hospital mortality. STUDY DESIGN: Adults (age 18 to 84 years)
      living in Shelby County, TN, were eligible for the study. Addresses of adults
      admitted to the only Level I trauma center in the county from 1996 to 2005 were
      geocoded and matched to 1 of 214 census tract groups. Census tract groups were
      divided into quintiles based on percent of the population living below the
      poverty level (lowest to highest income N-SES). Crude injury admission rate
      ratios (CIRR) and 95% confidence intervals (CI) were calculated. Multivariable
      logistic regression was used to determine if N-SES was associated with in
      hospital mortality. RESULTS: Compared with the highest N-SES, those in the lowest
      N-SES suffered significantly higher rates of blunt (CIRR 5.74; 95% CI 5.35, 6.15)
      and penetrating injuries (CIRR 20.98; 95% CI 18.03, 24.42). On multivariable
      logistic regression analysis, compared with the highest N-SES, decreasing N-SES
      was not associated with in-hospital mortality for blunt (high-middle [0.90; 95%
      CI 0.57, 1.44]; middle [1.22; 95% CI 0.78, 1.87]; low-middle [0.89; 95% CI 0.58,
      1.39]; lowest [0.67; 95% CI 0.42, 1.08]); or penetrating injury (high-middle
      [1.35; 95% CI 0.48, 3.81]; middle [2.77; 95% CI 0.99, 7.25]; low-middle [1.44;
      95% CI 0.55, 3.74]; and lowest [1.03; 95% CI 0.39, 2.73]). CONCLUSIONS: N-SES was
      inversely related to crude injury rates for all mechanisms. However, in-hospital
      mortality was not associated with N-SES level.

PMID- 20670861
TI  - Laparoscopic approach significantly reduces surgical site infections after
      colorectal surgery: data from national surgical quality improvement program.
AB  - BACKGROUND: The goal of this study was to compare surgical site infection (SSI)
      rates between laparoscopic (LAP) and open colorectal surgery using the National
      Surgical Quality Improvement Program (NSQIP) database. STUDY DESIGN: We
      identified patients included in the NSQIP database from 2006 to 2007 who
      underwent LAP and open colorectal surgery. SSI rates were compared for the 2
      groups. Association between patient demographics, diagnosis, type of procedure,
      comorbidities, laboratory values, intraoperative factors, and SSI within 30 days
      of surgery, were determined using a logistic regression analysis. RESULTS: Among
      10,979 patients undergoing colorectal surgery (LAP 31.1%, open 68.9%), the SSI
      rate was 14.0% (9.5% LAP vs 16.1% open, p < 0.001). LAP patients were younger (p
      < 0.001), with lower American Society of Anesthesiologists (ASA) scores (p <
      0.001) and comorbidities (p = 0.001) involving benign and inflammatory conditions
      rather than malignancy (p < 0.001), but operative time was greater (p = 0.001).
      On multivariate analysis age, ASA > or = 3, smoking, diabetes, operative time
      >180 minutes, appendicitis or diverticulitis, and regional enteritis diseases
      were found to be significantly associated with high SSI; the LAP approach was
      associated with a reduced SSI rate. CONCLUSIONS: The LAP approach is
      independently associated with a reduced SSI when compared with open surgery and
      should, when feasible, be considered for colon and rectal conditions.

PMID- 20670860
TI  - Predicting risk-adjusted mortality for trauma patients: logistic versus
      multilevel logistic models.
AB  - BACKGROUND: Theoretical advantages of random-intercept multilevel (ML) logistic
      regression (LR) modeling over standard LR include separating variability due to
      patient-level and hospital-level predictors, shrinkage of estimates for lower
      volume hospitals toward the overall mean, and fewer hospitals falsely identified
      as outliers. STUDY DESIGN: We used Nationwide Inpatient Sample data from 2002 to
      2004 to construct LR models of hospital mortality after admission with a
      principal ICD-9 Clinical Modification injury diagnosis (ICD-9 Clinical
      Modification codes 800 to 904, 910 to 929, 940 to 957, and 959). After
      considering various predictors, we used patient-level indicator variables for age
      groups, gender, maximum Abbreviated Injury Scale (AIS) for the head region (AIS
      score 3, 4, or 5), maximum AIS for other body regions (AIS score 3, 4, or 5), and
      mechanisms (eg, fall, gunshot, motor vehicle). Using standard LR and MLLR, we
      compared predictions based on 2002, 2003, and 2004 data with actual mortality
      observed in the same hospitals in the 2004, 2005, and 2006 Nationwide Inpatient
      Samples, respectively. RESULTS: Patient-level fixed effects were similar for the
      2 methods in all years, with mortality associated most strongly with AIS = 5 head
      injury, other AIS = 5 injury, or higher age groups. ML models identified fewer
      hospitals as outliers. Differences between actual and predicted mortality were
      smaller with MLLR models compared with standard LR models. CONCLUSIONS:
      Multilevel models might have advantages for the measurement and explanation of
      interhospital differences in trauma patient outcomes.

PMID- 20670862
TI  - Endoscopic treatment of Zenker diverticulum: results of a 7-year experience.
AB  - BACKGROUND: Zenker diverticulum (ZD) is a rare disease usually seen in elderly
      patients who present with symptoms of worsening dysphagia and regurgitation.
      Although open surgical approach is still the standard management for symptomatic
      patients, the endoscopic technique has evolved as an alternative approach,
      especially for highly morbid patients. We are reporting our experience for
      treating ZD using endoscopic needle-knife papillotome. STUDY DESIGN: A total of
      18 patients with a mean age of 80 years (range 68 to 91 years) were included in
      our prospective cohort study. All patients underwent endoscopic cricopharyngeal
      myotomy for symptomatic ZD using needle-knife papillotome at Brandon Regional
      Health Centre during a 7-year period. Mean follow-up was 27.5 months. A dysphagia
      score system from 0 (no dysphagia) to 4 (severe dysphagia) was used. All
      patients' baseline characteristics, pre- and postoperative symptoms, operative
      time, time to oral intake, length of hospital stay, recurrence of symptoms, and
      complications were analyzed. RESULTS: Dysphagia score and regurgitation symptoms
      improved substantially after treatment. Mean operative time was 28.4 minutes.
      Oral intake was resumed within 24 hours in all but 1 patient. Hospital stay for
      the majority was 24 to 48 hours. Only 1 patient had a microperforation treated
      conservatively and 2 patients had re-do procedures for persistence of dysphagia.
      CONCLUSIONS: Endoscopic cricopharyngeal myotomy using needle-knife papillotome is
      an effective approach to manage ZD for highly morbid patients. It is minimally
      invasive, decreases anesthetic time, shortens hospital stay, and has a low
      complication rate.

PMID- 20670863
TI  - Prospective study in 3,000 consecutive parathyroid operations demonstrates 18
      objective factors that influence the decision for unilateral versus bilateral
      surgical approach.
AB  - BACKGROUND: Although localizing studies are well-known predictors of which
      patients are candidates for unilateral versus bilateral parathyroid exploration,
      there are a number of other factors that have positive or negative influence
      preoperatively and intraoperatively. STUDY DESIGN: A prospective study was
      conducted during 20 months on 3,000 consecutive patients undergoing surgery for
      primary hyperparathyroidism to determine which factors caused the surgeons to
      explore bilaterally or, in contrast, influenced a unilateral approach. Seventeen
      preoperative and 5 intraoperative objective points were documented on all
      patients to see how decisions were made. RESULTS: Parathyroidectomy was
      unilateral in 32% and bilateral in 68%. Preoperative factors that had a positive
      predictive value in dictating a unilateral approach were (in decreasing
      frequency): positive sestamibi, previous parathyroid/thyroid surgery, age older
      than 80 years, anticoagulation medications, morbid obesity, and presence of large
      goiter (all p < 0.001). Preoperative parameters dictating a bilateral approach
      included negative sestamibi, more than one focus on sestamibi, contralateral
      thyroid disease, family history, lithium use, history of radiation, MEN, age
      younger than 20 years, and pregnancy (all p < 0.001). Intraoperative parameters
      influencing conversion of unilateral to bilateral were false-positive sestamibi,
      hormone measures not meeting sufficient levels, abnormal ipsilateral gland, and
      contralateral thyroid pathology identified (all p < 0.001). Factors that had no
      effect were gender, degree of calcium, and/or parathyroid hormone elevation, and
      age between 20 and 80 years. Cure rates were 99.9% for bilateral and 99.0% for
      unilateral (p = 0.057). CONCLUSIONS: High-volume surgeons use a number of
      identifiable objective factors to determine the best candidates for unilateral
      versus bilateral parathyroid exploration. Localizing studies such as sestamibi
      scans ultimately play a minor role in determining how many parathyroid glands are
      evaluated.

PMID- 20670864
TI  - A comparison of human cadaver and augmented reality simulator models for straight
      laparoscopic colorectal skills acquisition training.
AB  - BACKGROUND: The aim of this study was to compare the human cadaver model with an
      augmented reality simulator for straight laparoscopic colorectal skills
      acquisition. STUDY DESIGN: Thirty-five sigmoid colectomies were performed on a
      cadaver (n = 7) or an augmented reality simulator (n = 28) during a laparoscopic
      training course. Prior laparoscopic colorectal experience was assessed. Objective
      structured technical skills assessment forms were completed by trainers and
      trainees independently. Groups were compared according to technical skills and
      events scores and satisfaction with training model. RESULTS: Prior laparoscopic
      experience was similar in both groups. For trainers and trainees, technical
      skills scores were considerably better on the simulator than on the cadaver. For
      trainers, generic events score was also considerably better on the simulator than
      on the cadaver. The main generic event occurring on both models was errors in the
      use of retraction. The main specific event occurring on both models was bowel
      perforation. Global satisfaction was better for the cadaver than for the
      simulator model (p < 0.001). CONCLUSIONS: The human cadaver model was more
      difficult but better appreciated than the simulator for laparoscopic sigmoid
      colectomy training. Simulator training followed by cadaver training can
      appropriately integrate simulators into the learning curve and maintain the
      benefits of both training methodologies.

PMID- 20670865
TI  - Pre-operative gynecologic evaluation of bariatric surgery patients: improving
      cancer detection in a high-risk population.
AB  - BACKGROUND: Obesity is strongly associated with endometrial and breast cancers;
      further, obese women are less likely to undergo recommended cancer screening. The
      objective was to determine the preoperative practices of bariatric surgeons with
      regard to gynecologic assessment and cancer screening. STUDY DESIGN: A 28
      question survey was mailed to 1,503 US bariatric surgeons to assess self-reported
      perceptions of gynecologic cancer screening, preoperative evaluation of female
      patients, and gynecologic oncology awareness and knowledge. RESULTS: Of 1,503
      surgeons, 274 responded (18%) and 11 incomplete surveys were excluded, leaving
      263 (17%) for analysis. Mean surgeon age was 46.8 years. Surgeons averaged 13.9
      years postresidency and were predominantly male (89%). Eighty percent obtained
      gynecologic histories, but 56% and 49%, respectively, did not require Pap tests
      or mammograms before bariatric surgery. Only 21% had ever referred a patient for
      endometrial evaluation. Female surgeons were more likely to obtain menstrual and
      cancer-related family histories (p < 0.05). Surgeons who graduated from residency
      10 or more years ago were more likely to obtain a pregnancy history (p = 0.006).
      One-fifth of surgeons reported that they do not consistently counsel their
      patients about increased cancer risks due to obesity. Last, surgeons correctly
      identified the following signs and risk factors of endometrial cancer at variable
      rates: postmenopausal bleeding (99%), obesity (97%), irregular or heavy periods
      (69%), hereditary nonpolyposis colorectal cancer (21%), infertility (20.2%),
      diabetes (14.1%), and hypertension (4.9%). CONCLUSIONS: Given the massive
      increases in morbid obesity and bariatric surgery in women, surgeons could serve
      a vital role in educating patients about both gynecologic and nongynecologic
      malignancy risks. With appropriate referral for cancer screening, patient
      outcomes could improve.

PMID- 20670866
TI  - Peritoneal cytokines predict mortality after surgical treatment of secondary
      peritonitis in the rat.
AB  - BACKGROUND: The study aimed to analyze if peritoneal cytokine levels can predict
      survival in an experimental model for peritonitis. Early identification of
      patients most at risk for adverse outcomes would facilitate the decision for
      aggressive therapy in order to maximally exploit their chance for survival. STUDY
      DESIGN: Peritonitis was induced by intraperitoneal injection of a feces/bacteria
      mixture in 175 rats. Surgical debridement was performed after 1 hour. Abdominal
      fluid samples were taken after 24 and 72 hours for the measurement of interleukin
      (IL)-6, IL-10, and tumor necrosis factor (TNF)-alpha. Surviving animals were
      sacrificed after 5 days and correlations between cytokine levels and survival
      were analyzed. RESULTS: Altogether, 60 animals died prematurely, 12 before the
      first sampling of cytokines. So, 48 nonsurvivors and 115 survivors were analyzed.
      Peritoneal cytokine levels were much higher (p < 0.0001) in nonsurvivors than in
      survivors. At 24 hours there were strong correlations between cytokine levels,
      especially between IL-6 and IL-10 (r = 0.93). Peritoneal cytokines at 24 hours
      also discriminated between animals dying within the next 24 hours and those dying
      later. A strongly (p < 0.0001) increased mortality was observed if IL-6, IL-10,
      or TNF-alpha levels exceeded 2, 1, or 0.2 ng/mL, respectively. Receiver operating
      characteristic curves were promising for all 3, but IL-10 showed the best
      characteristics, with an area under the curve of 0.94 and 67% sensitivity at 95%
      specificity, obtained at a cut-off value of 1.26 ng/mL. CONCLUSIONS: These data
      should generate renewed interest to examine the peritoneal cytokines as early
      markers for adverse outcomes in patients with secondary peritonitis. Possibly,
      combinations of peritoneal cytokines with other markers can lead to much needed,
      reliable early prediction of disease severity.

PMID- 20670867
TI  - Sarcopenia and mortality after liver transplantation.
AB  - BACKGROUND: Surgeons frequently struggle to determine patient suitability for
      liver transplantation. Objective and comprehensive measures of overall burden of
      disease, such as sarcopenia, could inform clinicians and help avoid futile
      transplantations. STUDY DESIGN: The cross-sectional area of the psoas muscle was
      measured on CT scans of 163 liver transplant recipients. After controlling for
      donor and recipient characteristics using Cox regression models, we described the
      relationship between psoas area and post-transplantation mortality. RESULTS:
      Psoas area correlated poorly with Model for End-Stage Liver Disease score and
      serum albumin. Cox regression revealed a strong association between psoas area
      and post-transplantation mortality (hazard ratio = 3.7/1,000 mm(2) decrease in
      psoas area; p < 0.0001). When stratified into quartiles based on psoas area
      (holding donor and recipient characteristics constant), 1-year survival ranged
      from 49.7% for the quartile with the smallest psoas area to 87.0% for the
      quartile with the largest. Survival at 3 years among these groups was 26.4% and
      77.2%, respectively. The impact of psoas area on survival exceeded that of all
      other covariates in these models. CONCLUSIONS: Central sarcopenia strongly
      correlates with mortality after liver transplantation. Such objective measures of
      patient frailty, such as sarcopenia, can inform clinical decision making and,
      potentially, allocation policy. Additional work is needed develop valid and
      clinically relevant measures of sarcopenia and frailty in liver transplantation.

PMID- 20670868
TI  - American College of Surgeons International scholarship programs: 40-year history
      of support for International Surgical Education.

PMID- 20670869
TI  - Human Emotion and Response in Surgery (HEARS): a simulation-based curriculum for
      communication skills, systems-based practice, and professionalism in surgical
      residency training.
AB  - BACKGROUND: This study examines the development and implementation of a pilot
      human factors curriculum during a 2-year period. It is one component of a
      comprehensive 5-year human factors curriculum spanning core competencies of
      interpersonal and communication skills, systems-based practice, and
      professionalism and using low-and high-fidelity simulation techniques. STUDY
      DESIGN: Members of the Department of Surgery and the Center for Clinical
      Communication and Performance Outcomes jointly constructed a curriculum for PGY1
      and PGY2 residents on topics ranging from challenging communication to time and
      stress management. Video demonstrations, triggers, and simulated scenarios
      involving acting patients were created by surgeons and medical educators. Pre-
      and postintervention measures were obtained for communication skills, perceived
      stress level, and teamwork. Communication skills were evaluated using a series of
      video vignettes. The validated Perceived Stress Scale and Teamwork and Patient
      Safety Attitudes survey were used. Residents' perceptions of the program were
      also measured. RESULTS: Twenty-seven PGY1 residents and 15 PGY2 residents
      participated during 2 years. Analyses of video vignette tests indicated
      significant improvement in empathic communication for PGY1 (t = 3.62, p = 0.001)
      and PGY2 (t = 5.00, p = 0.004). There were no significant changes to teamwork
      attitudes. Perceived levels of stress became considerably higher. PGY1 residents
      reported trying 1 to 3 strategies taught in the time management session, with 60%
      to 75% reporting improvement post-training. CONCLUSIONS: This unique and
      comprehensive human factors curriculum is shown to be effective in building
      communication competency for junior-level residents in the human and emotional
      aspects of surgical training and practice. Continued refinement and ongoing data
      acquisition and analyses are underway.

PMID- 20670870
TI  - Radiofrequency ablation use in hepatocellular carcinoma.

PMID- 20670872
TI  - Impact of obesity on outcomes after open surgical and endovascular abdominal
      aortic aneurysm repair.

PMID- 20670874
TI  - Hands-free technique and sharps injuries in surgical settings.

PMID- 20670875
TI  - Occupational Safety and Health Administration urges surgeons to reduce sharps
      injuries in the surgical setting.

PMID- 20670876
TI  - Risk-adjusted outcomes database as a tool to promote horizontal integration of
      surgical systems in low- and middle-income countries.

PMID- 20670877
TI  - Factors Dominating Choice of Surgical Specialty among Foreign Medical Graduates.

PMID- 20670880
TI  - Evidence for enhanced characterization of cortical bone using novel pQCT shape
      software.
AB  - Bone shape, mass, structural geometry, and material properties determine bone
      strength. This study describes novel software that uses peripheral quantitative
      computed tomography (pQCT) images to quantify cortical bone shape and
      investigates whether the combination of shape-sensitive and manufacturer's
      software enhances the characterization of tibiae from contrasting populations.
      Existing tibial pQCT scans (4% and 50% sites) from Gambian (n=38) and British
      (n=38) women were used. Bone mass, cross-sectional area (CSA), and geometry were
      determined using manufacturer's software; cross-sectional shape was quantified
      using shape-sensitive software. At 4% site, Gambian women had lower total bone
      mineral content (BMC: -15.4%), CSA (-13.4%), and trabecular bone mineral density
      (BMD: -19%), but higher cortical subcortical BMD (6.1%). At 50% site, Gambian
      women had lower cortical BMC (-7.6%), cortical CSA (-12.6%), and mean cortical
      thickness (-15.0%), but higher cortical BMD (4.9%) and endosteal circumference
      (8.0%). Shape-sensitive software supported the finding that Gambian women had
      larger tibial endosteal circumference (9.8%), thinner mean cortical thickness (
      26.5%) but smaller periosteal circumference (-5.6%). Shape-sensitive software
      revealed that Gambian women had tibiae with shorter maximum width (-7.6%) and
      thinner cortices (-22% to -41.2%) and more closely resembled a circle or ellipse.
      Significant differences remained after adjusting for age, height, and weight. In
      conclusion, shape-sensitive software enhanced the characterization of tibiae in 2
      contrasting groups of women.

PMID- 20670881
TI  - Bone mineral density results influencing health-related behaviors in male
      athletes at risk for osteoporosis.
AB  - The purposes of this study were to determine the role of bone mineral density
      (BMD) and mood in influencing health-related behaviors of serious leisure male
      athletes (cyclists and triathletes) at risk for osteoporosis. A cross-sectional
      design evaluated BMD in 18-60-yr-old serious leisure male cyclists by dual-energy
      X-ray adsorptiometry (DXA). Activity was measured using the International
      Physical Activity Questionnaire; personality was assessed using the NEO-60; and
      quality of life using Short-Form Health 12 (SF-12). Participants completed an
      online survey questionnaire after completing their DXA testing a minimum of 3 mo
      before assessing health-related behaviors and general attitudes toward general
      health and well-being. Forty-two (61.9%) participants responded to the follow-up
      questionnaire. Serious leisure male athletes are more likely to initiate
      significant health-related behavioral changes after learning of their bone
      density results including calcium supplementation and weight-bearing exercise.
      Men with low BMD (LBMD) had higher openness subscales on NEO-60 compared with men
      with normal BMD. SF-12 mental and physical health scores were significantly lower
      in men with LBMD. Perhaps, the interaction and interplay of genetics, activity
      and behaviors, and aspects of mental and psychological functions contribute to
      their reduction in BMD and heightened risk for fracture. Findings from this study
      suggest that early BMD testing in "serious athletes" has important clinical
      relevance for their potential risk for osteoporosis in the future.

PMID- 20670882
TI  - Estimation of total-body and regional soft tissue composition from DXA bone
      densitometry of the lumbar spine and hip.
AB  - The percent fat in soft tissues adjacent to the lumbar spine and proximal femur,
      which are required parameters in the calculation of bone mineral by conventional
      dual-energy X-ray absorptiometry (DXA) of the spine and hip, were analyzed for
      their relationship with the total-body soft tissue-scanning derivatives. The
      cohort (N=149), consisting of stable actively treated male human immunodeficiency
      virus HIV-positive patients, was split in half to obtain prediction equations
      with one half to be validated by the other half. Prediction equations for the
      dependent variables total-body fat, total-body lean mass, trunk fat, total arm +
      leg fat, and leg fat were derived by step-down multiple regression. A Bland
      Altman comparison of the predicted and observed values showed that the limits of
      agreement were too large to be clinically helpful. The correlations of the ratio
      of adjacent spine/hip fat with ratios of trunk/arm + leg fat and trunk/leg fat,
      markers of peripheral lipoatrophy in HIV, were 0.725 and 0.780, respectively. The
      3 ratios were compared with the clinical diagnosis of the presence or absence of
      peripheral lipoatrophy by receiver operating characteristic analysis. The area
      under the curve was 0.720 for adjacent spine/hip fat ratio and 0.655 and 0.699
      for trunk/arm + leg fat and trunk/leg fat, respectively; they were not
      significantly different. In conclusion, for male HIV-positive patients, the
      difference between predicted values and actual values rendered limits of
      agreement that were too wide to be clinically acceptable. The ratio of percent
      fat in the lumbar spine region to percent fat in the proximal femur region
      reflected the presence of peripheral lipoatrophy as effectively as the
      trunk/peripheral fat ratio that was derived from the total-body scan.

PMID- 20670883
TI  - Chaperones get RISC loaded.

PMID- 20670884
TI  - Repair scaffolding reaches new heights at blocked replication forks.
AB  - In this issue of Molecular Cell, Ohouo et al. (2010) show that Mec1 (hATR)
      promotes the association of Slx4 and Rtt107 with Dpb11 (hTopBP1) in response to
      MMS-induced DNA alkylation, suggesting that Slx4 and Rtt107 might coordinate
      repair factors specifically at damaged replication forks.

PMID- 20670885
TI  - Dangerous liaisons: Fanconi anemia and toxic nonhomologous end joining in DNA
      crosslink repair.
AB  - The proper choice of repair pathway is critical to tolerating various types of
      DNA damage. In a recent issue of Molecular Cell, Adamo et al. (2010), along with
      a second report (Pace et al., 2010), describe how the Fanconi anemia (FA) pathway
      is involved in preventing aberrant DNA repair. These studies suggest a
      potentially significant new opportunity for the treatment of FA.

PMID- 20670886
TI  - DNA repair has a new FAN1 club.
AB  - In recent issues of Molecular Cell, Cell, and Science, Smogorzewska et al.
      (2010), MacKay et al. (2010), Kratz et al. (2010), and Liu et al. (2010) identify
      FAN1 as a nuclease that is recruited to sites of interstrand crosslinks by
      ubiquitylated FANCD2, where it participates in DNA repair. The identification of
      FAN1 fills a missing link in interstrand crosslink DNA repair.

PMID- 20670887
TI  - Activation of a metabolic gene regulatory network downstream of mTOR complex 1.
AB  - Aberrant activation of the mammalian target of rapamycin complex 1 (mTORC1) is a
      common molecular event in a variety of pathological settings, including genetic
      tumor syndromes, cancer, and obesity. However, the cell-intrinsic consequences of
      mTORC1 activation remain poorly defined. Through a combination of unbiased
      genomic, metabolomic, and bioinformatic approaches, we demonstrate that mTORC1
      activation is sufficient to stimulate specific metabolic pathways, including
      glycolysis, the oxidative arm of the pentose phosphate pathway, and de novo lipid
      biosynthesis. This is achieved through the activation of a transcriptional
      program affecting metabolic gene targets of hypoxia-inducible factor (HIF1alpha)
      and sterol regulatory element-binding protein (SREBP1 and SREBP2). We find that
      SREBP1 and 2 promote proliferation downstream of mTORC1, and the activation of
      these transcription factors is mediated by S6K1. Therefore, in addition to
      promoting protein synthesis, mTORC1 activates specific bioenergetic and anabolic
      cellular processes that are likely to contribute to human physiology and disease.

PMID- 20670888
TI  - Transnitrosylation of XIAP regulates caspase-dependent neuronal cell death.
AB  - X-linked inhibitor of apoptosis (XIAP) is a potent antagonist of caspase
      apoptotic activity. XIAP also functions as an E3 ubiquitin ligase, targeting
      caspases for degradation. However, molecular pathways controlling XIAP activities
      remain unclear. Here, we report that nitric oxide (NO) reacts with XIAP by S
      nitrosylating its RING domain (forming SNO-XIAP), thereby inhibiting E3 ligase
      and antiapoptotic activity. NO-mediated neurotoxicity and caspase activation have
      been linked to several neurodegenerative disorders, including Alzheimer's,
      Parkinson's, and Huntington's diseases. We find significant SNO-XIAP formation in
      brains of patients with these diseases, implicating this reaction in the etiology
      of neuronal damage. Conversely, S-nitrosylation of caspases is known to inhibit
      apoptotic activity. Unexpectedly, we find that SNO-caspase transnitrosylates
      (transfers its NO group) to XIAP, forming SNO-XIAP, and thus promotes cell injury
      and death. These findings provide insights into the regulation of caspase
      activation in neurodegenerative disorders mediated, at least in part, by
      nitrosative stress.

PMID- 20670889
TI  - Defining the pathway of cytoplasmic maturation of the 60S ribosomal subunit.
AB  - In eukaryotic cells the final maturation of ribosomes occurs in the cytoplasm,
      where trans-acting factors are removed and critical ribosomal proteins are added
      for functionality. Here, we have carried out a comprehensive analysis of
      cytoplasmic maturation, ordering the known steps into a coherent pathway.
      Maturation is initiated by the ATPase Drg1. Downstream, assembly of the ribosome
      stalk is essential for the release of Tif6. The stalk recruits GTPases during
      translation. Because the GTPase Efl1, which is required for the release of Tif6,
      resembles the translation elongation factor eEF2, we suggest that assembly of the
      stalk recruits Efl1, triggering a step in 60S biogenesis that mimics aspects of
      translocation. Efl1 could thereby provide a mechanism to functionally check the
      nascent subunit. Finally, the release of Tif6 is a prerequisite for the release
      of the nuclear export adaptor Nmd3. Establishing this pathway provides an
      important conceptual framework for understanding ribosome maturation.

PMID- 20670890
TI  - PoxA, yjeK, and elongation factor P coordinately modulate virulence and drug
      resistance in Salmonella enterica.
AB  - We report an interaction between poxA, encoding a paralog of lysyl tRNA
      synthetase, and the closely linked yjeK gene, encoding a putative 2,3-beta-lysine
      aminomutase, that is critical for virulence and stress resistance in Salmonella
      enterica. Salmonella poxA and yjeK mutants share extensive phenotypic pleiotropy,
      including attenuated virulence in mice, an increased ability to respire under
      nutrient-limiting conditions, hypersusceptibility to a variety of diverse growth
      inhibitors, and altered expression of multiple proteins, including several
      encoded on the SPI-1 pathogenicity island. PoxA mediates posttranslational
      modification of bacterial elongation factor P (EF-P), analogous to the
      modification of the eukaryotic EF-P homolog, eIF5A, with hypusine. The
      modification of EF-P is a mechanism of regulation whereby PoxA acts as an
      aminoacyl-tRNA synthetase that attaches an amino acid to a protein resembling
      tRNA rather than to a tRNA.

PMID- 20670891
TI  - Human LSD2/KDM1b/AOF1 regulates gene transcription by modulating intragenic
      H3K4me2 methylation.
AB  - Dynamic histone H3K4 methylation is an important epigenetic component of
      transcriptional regulation. However, most of our current understanding of this
      histone mark is confined to the regulation of transcriptional initiation. We now
      show that human LSD2/KDM1b/AOF1, the human homolog of LSD1, is an H3K4me1/2
      demethylase that specifically regulates histone H3K4 methylation within
      intragenic regions of its target genes. Genome-wide mapping reveals that LSD2
      associates predominantly with the gene bodies of actively transcribed genes, but
      is markedly absent from promoters. Depletion of endogenous LSD2 results in an
      increase of H3K4me2 as well as a decrease of H3K9me2 at LSD2-binding sites and a
      consequent dysregulation of target gene transcription. Furthermore,
      characterization of the LSD2 complex reveals that LSD2 forms active complexes
      with euchromatic histone methyltransferases G9a and NSD3 as well as cellular
      factors involved in transcription elongation. These data provide a possible
      molecular mechanism linking LSD2 to transcriptional regulation after initiation.

PMID- 20670892
TI  - Phosphorylated Pol II CTD recruits multiple HDACs, including Rpd3C(S), for
      methylation-dependent deacetylation of ORF nucleosomes.
AB  - Methylation of histone H3 by Set1 and Set2 is required for deacetylation of
      nucleosomes in coding regions by histone deacetylase complexes (HDACs) Set3C and
      Rpd3C(S), respectively. We report that Set3C and Rpd3C(S) are cotranscriptionally
      recruited in the absence of Set1 and Set2, but in a manner stimulated by Pol II
      CTD kinase Cdk7/Kin28. Consistently, Rpd3C(S) and Set3C interact with Ser5
      phosphorylated Pol II and histones in extracts, but only the histone interactions
      require H3 methylation. Moreover, reconstituted Rpd3C(S) binds specifically to
      Ser5-phosphorylated CTD peptides in vitro. Hence, whereas interaction with
      methylated H3 residues is required for Rpd3C(S) and Set3C deacetylation
      activities, their cotranscriptional recruitment is stimulated by the
      phosphorylated CTD. We further demonstrate that Rpd3, Hos2, and Hda1 have
      overlapping functions in deacetylating histones and suppressing cotranscriptional
      histone eviction. A strong correlation between increased acetylation and lower
      histone occupancy in HDA mutants implies that histone acetylation is important
      for nucleosome eviction.

PMID- 20670893
TI  - SIRT1 regulates UV-induced DNA repair through deacetylating XPA.
AB  - SIRT1, a NAD(+)-dependent histone deacetylase, plays crucial roles in multiple
      biological processes including gene transcription, cellular metabolism, stress
      response, and tumorigenesis. Xeroderma pigmentosum group A (XPA) is a core
      nucleotide excision repair (NER) factor essential for NER process. Here we show
      that SIRT1 plays an important role in the regulation of NER pathway.
      Downregulation of SIRT1 significantly sensitizes cells to UV irradiation. SIRT1
      interacts with XPA, and the interaction is enhanced after UV irradiation. XPA can
      be acetylated at lysines 63 and 67. SIRT1 deacetylates XPA both in vitro and in
      cells. Importantly, SIRT1-mediated deacetylation of XPA is required for optimal
      NER pathway since XPA-deficient cells complemented with XPA-K6367Q, which mimics
      hyperacetylated XPA, display significantly higher UV sensitivity compared with
      the XPA cells complemented with wild-type XPA. Furthermore, SIRT1-mediated XPA
      deacetylation enhances its interaction with RPA32. Our results demonstrate that
      SIRT1 regulates NER pathway through modulation of XPA acetylation status.

PMID- 20670894
TI  - The FANCM/FAAP24 complex is required for the DNA interstrand crosslink-induced
      checkpoint response.
AB  - Cells from Fanconi anemia (FA) patients are extremely sensitive to DNA
      interstrand crosslinking (ICL) agents, but the molecular basis of the
      hypersensitivity remains to be explored. FANCM (FA complementation group M), and
      its binding partner, FAAP24, anchor the multisubunit FA core complex to chromatin
      after DNA damage and may contribute to ICL-specific cellular response. Here we
      show that the FANCM/FAAP24 complex is specifically required for the recruitment
      of replication protein A (RPA) to ICL-stalled replication forks. ICL-induced RPA
      foci formation requires the DNA-binding activity of FAAP24 but not the DNA
      translocase activity of FANCM. Furthermore, FANCM/FAAP24-dependent RPA foci
      formation is required for efficient ATR-mediated checkpoint activation in
      response to ICL. Therefore, we propose that FANCM/FAAP24 plays a role in ICL
      induced checkpoint activation through regulating RPA recruiment at ICL-stalled
      replication forks.

PMID- 20670895
TI  - Structural basis for assembly of Hsp90-Sgt1-CHORD protein complexes: implications
      for chaperoning of NLR innate immunity receptors.
AB  - Hsp90-mediated function of NLR receptors in plant and animal innate immunity
      depends on the cochaperone Sgt1 and, at least in plants, on a cysteine- and
      histidine-rich domains (CHORD)-containing protein Rar1. Functionally, CHORD
      domains are associated with CS domains, either within the same protein, as in the
      mammalian melusin and Chp1, or in separate but interacting proteins, as in the
      plant Rar1 and Sgt1. Both CHORD and CS domains are independently capable of
      interacting with the molecular chaperone Hsp90 and can coexist in complexes with
      Hsp90. We have now determined the structure of an Hsp90-CS-CHORD ternary complex,
      providing a framework for understanding the dynamic nature of Hsp90-Rar1-Sgt1
      complexes. Mutational and biochemical analyses define the architecture of the
      ternary complex that recruits nucleotide-binding leucine-rich repeat receptors
      (NLRs) by manipulating the structural elements to control the ATPase-dependent
      conformational cycle of the chaperone.

PMID- 20670896
TI  - DNA damage signaling recruits the Rtt107-Slx4 scaffolds via Dpb11 to mediate
      replication stress response.
AB  - The DNA damage checkpoint kinase Mec1(ATR) is critical for maintaining the
      integrity of replication forks. Though it has been proposed to promote fork
      repair, the mechanisms by which Mec1 regulates DNA repair factors remain unclear.
      Here, we found that Mec1 mediates a key interaction between the fork protein
      Dpb11 and the DNA repair scaffolds Slx4-Rtt107 to regulate replication stress
      response. Dissection of the molecular basis of the interaction reveals that Slx4
      and Rtt107 jointly bind Dpb11 and that Slx4 phosphorylation is required. Mutation
      of Mec1 phosphorylation sites in Slx4 disrupts its interaction with Dpb11 and
      compromises the cellular response to replisomes blocked by DNA alkylation.
      Multiple fork repair factors associate with Rtt107 or Slx4, supporting that Mec1
      dependent assembly of the Rtt107-Slx4-Dpb11 complex functions to coordinate fork
      repair. Our results unveil how Mec1 regulates the Slx4 and Rtt107 scaffolds and
      establish a mechanistic link between DNA damage signaling and fork repair.

PMID- 20670898
TI  - WHO failing in duty of transparency.

PMID- 20670897
TI  - The terminal telomeric DNA sequence determines the mechanism of dysfunctional
      telomere fusion.
AB  - Mammalian telomeres consist of tandem DNA repeats that bind protective protein
      factors collectively termed shelterins. Telomere disruption typically results in
      genome instability induced by telomere fusions. The mechanism of telomere fusion
      varies depending on the means of telomere disruption. Here, we investigate
      telomere fusions caused by overexpression of mutant telomerases that add mutated
      telomeric repeats, thereby compromising shelterin binding to telomeric termini.
      While all mutant telomeric sequences tested induced heterodicentric chromosome
      fusions in ATM-competent cells, only those mutant repeat sequences with
      significant self complementarity induced ATM-independent sister chromatid and
      isodicentric chromosome fusions. Thus, once a telomere becomes dysfunctional, the
      terminal telomeric sequence itself determines the fate of that telomere. These
      results suggest that annealing of self-complementary DNA sequence engages an
      alternative telomere fusion pathway in human cells, and provide one explanation
      for the conspicuous lack of self complementarity in the majority of known
      naturally occurring eukaryotic telomeric sequences.

PMID- 20670899
TI  - Bone-marrow uptake of (18)F-FDG during fever.

PMID- 20670901
TI  - If a pig coughs in Mexico the whole world should hear it.

PMID- 20670902
TI  - Out of sight, out of mind?

PMID- 20670903
TI  - Chagas disease: changes in knowledge and management.
AB  - More than 100 years after the discovery of human American trypanosomiasis by
      Carlos Chagas, our knowledge and management of the disease are profoundly
      changing. Substantial progress made by disease control programmes in most endemic
      areas contrasts with persisting difficulties in the Gran Chaco region in South
      America and the recent emergence of the disease in non-endemic areas because of
      population movements. In terms of pathogenesis, major discoveries have been made
      about the life cycle and genomics of Trypanosoma cruzi, and the role of the
      parasite itself in the chronic phase of the disease. From a clinical perspective,
      a growing number of arguments have challenged the notion of an indeterminate
      phase, and suggest new approaches to manage patients. New methods such as
      standardised PCR will be necessary to ensure follow-up of this chronic infection.
      Although drugs for treatment of Chagas disease are limited, poorly tolerated, and
      not very effective, treatment indications are expanding. The results of the
      Benznidazole Evaluation For Interrupting Trypanosomiasis (BENEFIT) trial in 2012
      will also help to inform treatment. Mobilisation of financial resources to fund
      research on diagnosis and randomised controlled trials of treatment are
      international health priorities.

PMID- 20670904
TI  - The tinea capitis campaign in Serbia in the 1950s.
AB  - In this Historical Review we describe the 1950-59 UNICEF-supported campaign to
      eliminate tinea capitis, also known as ringworm, in Yugoslavia. Medical treatment
      for this infectious disease involved the use of ionising radiation. We discuss
      the possible health implications for the treated population. Data were collected
      from archive documents, newspapers from the 1950s, Yugoslavian scientific
      reports, interviews with patients who received treatment, and interviews with
      physicians who gave treatment during the campaign. The campaign screened 878 659
      individuals and treated 49 389. On the basis of Israeli tinea capitis research,
      late health consequences (mainly cancer in the irradiated area) can be expected
      in the treated Serbian population. The discovery of treatment records for a
      substantial number of patients makes public-health action and further research
      possible. The findings are relevant to the Serbian medical community and
      populations in other countries that used a radiation-based technique for the
      treatment of tinea capitis.

PMID- 20670905
TI  - Transferrin receptor 1: a ferritin receptor as well?

PMID- 20670906
TI  - Abdominal pain in a young man with severe hypertension.

PMID- 20670907
TI  - Electroporation enhances immune responses and protection induced by a bovine
      viral diarrhea virus DNA vaccine in newborn calves with maternal antibodies.
AB  - Bovine viral diarrhea virus (BVDV) is one of the major pathogens in cattle. In
      this study, newborn calves with maternal antibodies were vaccinated with a BVDV
      DNA vaccine, either by conventional intramuscular (IM) injection or with the
      TriGridTM Delivery System for IM delivery (TDS-IM). The calves vaccinated with
      the TDS-IM developed more rapidly and effectively BVDV-specific humoral and cell
      mediated immune responses in the presence of maternal antibodies. Overall, the
      immune responses induced by delivery with the TDS-IM remained stronger than those
      elicited by conventional IM injection of the BVDV DNA vaccine. Accordingly,
      electroporation-mediated delivery of the BVDV DNA vaccine resulted in close to
      complete protection from clinical signs of disease, while conventional IM
      administration did not fully prevent morbidity and mortality following challenge
      with BVDV-2. These results demonstrate the TDS-IM to be effective as a delivery
      system for a BVDV DNA vaccine in newborn calves in the presence of maternal
      antibodies, which supports the potential of electroporation as a delivery method
      for prophylactic DNA vaccines.

PMID- 20670908
TI  - Salmonella enterica serovar Typhimurium ruvB mutant can confer protection against
      salmonellosis in mice.
AB  - Salmonella enterica is an important pathogen that causes a variety of infectious
      diseases in animals and humans. Live attenuated vaccines generally confer better
      protection than killed or subunit vaccines; however, the former are limited by
      their inherent toxicity. We evaluated the potential of a novel candidate
      Salmonella vaccine strain that lacks the ruvB gene. The ruvB gene encodes a
      Holliday junction helicase that is required to resolve junctions that arise
      during the repair of non-arresting lesions after DNA replication. The deletion of
      this gene in Salmonella significantly impaired cell survival and proliferation
      within epithelial cells and macrophages. The defective virulence in ruvB mutant
      may be partially due to decreased expression of ssaG, a Salmonella pathogenicity
      island-2 gene, and increased sensitivity to hydrogen peroxide in the lack of ruvB
      gene. The virulence of the ruvB-deleted mutant was also greatly attenuated in
      BALB/c mice. The ruvB mutant conferred strong and durable immune-based protection
      against a challenge with a lethal dose of a virulent strain of Salmonella
      Typhimurium. Moreover, protective immunity was induced by a single dose of the
      vaccine, and the efficacy of protection was maintained for at least 6 months.
      These results suggest the use of the S. Typhimurium ruvB mutant as a novel
      vaccine.

PMID- 20670909
TI  - A randomized clinical trial assessing immunogenicity and safety of a double dose
      of virosomal-adjuvanted influenza vaccine administered to unprimed children aged
      6-35 months.
AB  - This study evaluated the immunogenicity of a double dose of the seasonal
      virosomal-adjuvanted influenza vaccine (Inflexal V, Crucell, The Netherlands) in
      65 previously unvaccinated children aged less than 3 years: 43 received double
      doses (two doses of 0.50 mL 4 weeks apart) and 22 standard doses (two doses of
      0.25 mL 4 weeks apart). Both treatments evoked a response that satisfied the EMEA
      criteria for adequate immunogenicity for all three vaccine strains, but the
      double dose had a significantly greater effect on all of the studied parameters
      of humoral and cell-mediated immune response (p<0.05). This result was achieved
      without any increase in the incidence of local and systemic adverse events. This
      means that doubling the dose of the virosomal-adjuvanted influenza vaccine (i.e.
      administering the same dose as that usually given to older children) effectively
      and safely increases the immune response to inactivated influenza vaccine in
      unprimed children aged less than 3 years.

PMID- 20670910
TI  - Potency against enterotoxemia of a recombinant Clostridium perfringens type D
      epsilon toxoid in ruminants.
AB  - Enterotoxemia, a disease that affects domestic ruminants, is caused mainly by the
      epsilon toxin from Clostridium perfringens type D. Its eradication is virtually
      impossible, control and prophylaxis are based on systematic vaccination of herds
      with epsilon toxoids that are efficient in inducing protective antibody
      production. The use of recombinant toxins is one of the most promising of these
      strategies. This work evaluates the potency of a Cl. perfringens type D epsilon
      toxoid expressed by Escherichia coli administered to goats, sheep, and cattle.
      The etx gene was cloned into the pET-11a plasmid of E. coli strain BL21 to
      produce the recombinant toxin. Rabbits (n=8), goats, sheep, and cattle (n=5 for
      each species) were immunized with 0.2mg of the insoluble recombinant protein
      fraction to evaluate vaccine potency of the epsilon toxoid studied. Antibody
      titers were 40, 14.3, 26, and 13.1 IU/mL in the rabbit, goat, sheep, and cattle
      serum pools, respectively. The epsilon toxoid produced and tested in this work is
      adequate for immunization of ruminants against enterotoxemia.

PMID- 20670911
TI  - The Pragmatic-Explanatory Continuum Indicator Summary (PRECIS) instrument was
      useful for refining a randomized trial design: experiences from an investigative
      team.
AB  - OBJECTIVE: A recently published instrument (PRECIS) was designed to assist
      investigative teams in understanding the various design decisions that need to be
      made regarding pragmatic vs. explanatory trials. Our team used this instrument
      during an investigators' meeting to organize our discussion regarding the design
      of a planned trial and to determine the extent of consensus among the study
      investigators. STUDY DESIGN AND SETTING: The study was descriptive in nature and
      occurred during an investigator meeting. After reading and reviewing the 10
      PRECIS criteria, the team made quantitative judgments of the planned study
      regarding each PRECIS criteria to reflect initial, ideal, and final study design
      perceptions. RESULTS: Data indicated that the final study design was more
      explanatory in nature than the preliminary plan. Evidence of consensus was
      obtained. CONCLUSION: The investigative team found that applying PRECIS
      principles were useful for (1) detailing points of discussion related to trial
      design, (2) making revisions to the design to be consistent with the project
      goals, and (3) achieving consensus. We believe our experiences with PRECIS may
      prove valuable for trial researchers in much the same way that case reports can
      provide valuable insights for clinicians.

PMID- 20670912
TI  - Diversity of views from Europe on national preparticipation screening for
      competitive athletes.

PMID- 20670913
TI  - Microbial systematics and taxonomy: relevance for a microbial commons.
AB  - The issues of microbial taxonomy and potential interactions with a microbial
      commons are discussed, with emphasis on three components: characterization;
      classification; and nomenclature. The current state of technology and the
      spectrum of methods that are used for phenotypic and genotypic characterization
      of prokaryotes, classification at different taxonomic levels and points of
      prokaryote nomenclature are reviewed. While all taxonomic ranks comprise a
      cohesive systematic framework for microorganisms, the prokaryotic genus and
      species provide the "working unit" of taxonomy. Since 2004, the number of validly
      published genera and species has increased by approximately 50%. Extensive
      development of technology will continue to enable ever higher resolution
      characterization and more refined classification of microorganisms.
      Characterization and classification at the species level may be most relevant for
      bacterial taxonomy, although reproducible differentiation at the strain level
      will probably prove to be more relevant for a microbial commons. A dynamic
      microbial taxonomy, albeit with well-founded and stable guidelines for defining
      microorganisms, provides an efficient organizational system for dealing with the
      enormous spectrum of microbial diversity.

PMID- 20670914
TI  - DNA-binding and transcriptional activities of human HSF4 containing mutations
      that associate with congenital and age-related cataracts.
AB  - Heat shock transcription factor HSF4 is necessary for ocular lens development and
      fiber cell differentiation. Mutations of the human HSF4 gene have been implicated
      in congenital and age-related cataracts. Here, we show that HSF4 activates
      transcription of genes encoding crystallins and beaded filament structural
      proteins in lens epithelial cells. Five missense mutations that have been
      associated with congenital cataract inhibited DNA-binding of HSF4, which
      demonstrates the relationship between HSF4 mutations, loss of lens protein gene
      expression, and cataractogenesis. However, two missense mutations that have been
      associated with age-related cataract did not or only slightly alter HSF4
      activity, implying that other genetic and environmental factors affect the
      functions of these mutant proteins.

PMID- 20670915
TI  - The levels of both lipid rafts and raft-located acetylcholinesterase dimers
      increase in muscle of mice with muscular dystrophy by merosin deficiency.
AB  - Wild type and dystrophic (merosin-deficient) Lama2dy mice muscles were compared
      for their density of lipid rafts. The 5-fold higher level of caveolin-3 and the 2
      3 times higher level of ecto-5'-nucleotidase activity in raft preparations
      (Triton X-100-resistant membranes) of dystrophic muscle supported expansion of
      caveolar and non-caveolar lipid rafts. The presence in rafts of
      glycosylphosphatidylinositol (GPI)-linked acetylcholinesterase (AChE) dimers,
      which did not arise from erythrocyte or nerve, not only revealed for the first
      time the capacity of the myofibre for translating the AChE-H mRNA but also an
      unrecognized pathway for targeting AChE-H to specialized membrane domains of the
      sarcolemma. Rafts of dystrophic muscle contained a 5-fold higher AChE activity/mg
      protein. RT-PCR for 3'-alternative mRNAs of AChE revealed AChE-T mRNA prevailing
      over AChE-R and AChE-H mRNAs in wild type mouse muscle. It also displayed
      principal 5'-alternative AChE mRNAs with exons E1c and E1e (the latter coding for
      N-terminally extended subunits) and fewer with E1d, E1a and E1b. The levels of
      AChE and butyrylcholinesterase mRNAs were unaffected by dystrophy. Finally, the
      decreased level of proline-rich membrane anchor (PRiMA) mRNA in Lama2dy muscle
      provided for a rational explanation to the loss of PRiMA-bearing AChE tetramers
      in dystrophic muscle.

PMID- 20670916
TI  - cAMP-mediated regulation of HNF-4alpha depends on the level of coactivator PGC
      1alpha.
AB  - Hepatocyte nuclear factor-4 alpha (HNF-4alpha) is a member of the nuclear
      receptor superfamily with important roles in hepatic metabolism. Fasting induces
      the cAMP/protein kinase A (PKA)-signaling pathway. The mechanisms whereby cAMP
      regulates HNF-4alpha transcriptional activity are incompletely understood. We
      have therefore investigated the role of cAMP/PKA in regulation of HNF-4alpha in
      COS-1 cells and the hepatoma HepG2 cell line. cAMP/PKA inhibited the
      transcriptional activity of HNF-4alpha in COS-1 cells, whereas a stimulatory
      effect was observed in HepG2 cells. The cAMP-induced inhibition of HNF-4alpha in
      COS-1 cells was counteracted by overexpression of the nuclear receptor
      coactivator PGC-1alpha, and cAMP/PKA-dependent induction of the PGC1A gene in
      HepG2 cells seems to explain the cell specific differences. This was further
      supported by knock-down of PGC-1alpha in HepG2 cells, which abolished the
      stimulatory effect of PKA on HNF-4alpha transcriptional activity. Similar to the
      cAMP/PKA-mediated regulation of HNF-4alpha, overexpression of the cAMP-response
      element binding protein (CREB) inhibited the transcriptional activity of HNF
      4alpha in COS-1 cells, regardless of cAMP/PKA activation and CREB
      phosphorylation. Moreover, activation of CREB by cAMP/PKA further stimulated HNF
      4alpha transactivation in HepG2 cells. cAMP induced the expression of the HNF
      4alpha target genes PCK1 and G6Pase in these cells. In conclusion, our results
      suggest that the level of PGC-1alpha determines whether the cAMP/PKA-pathway
      overall stimulates or inhibits HNF-4alpha transcriptional activation.

PMID- 20670917
TI  - Anxiolytic-like effect of the monoterpene 1,4-cineole in mice.
AB  - Recent studies have shown that some monoterpenes exert anxiolytic- and depressant
      like actions, however, these effects from monoterpene 1,4-cineole are still
      unknown. This work aimed to study the effects of 1,4-cineole in classic animal
      models for depression- and anxiety-like behavior, specifically the elevated plus
      maze (EPM), hole board, open field, pentobarbital sleeping time, forced swimming,
      tail suspension and rota rod tests. 1,4-Cineole was administered orally to mice
      (100, 200 and 400 mg/kg), while diazepam (1 or 2 mg/kg) and imipramine (10 or 30
      mg/kg) were used as standard drugs. 1,4-Cineole (400 mg/kg) modified all
      parameters observed in the EPM, while no significant variation was observed on
      general motor activity in the open-field test. In the hole-board assay, 1,4
      cineole induced increase on the number of head dips. Forced swimming and tail
      suspension tests showed that cineole (200 and/or 400 mg/kg) was able to promote
      significant increase on the immobility time, while a decreased sleep latency was
      observed (200 and 400 mg/kg ) on the pentobarbital sleeping time. Cineole had no
      effect on the motor coordination of animals in the rota rod test. The results
      suggest that 1,4-cineole presents potential anxiolytic-like action consistent
      with possible general depression of the CNS.

PMID- 20670918
TI  - Apomorphine conditioning and sensitization: the paired/unpaired treatment order
      as a new major determinant of drug conditioned and sensitization effects.
AB  - Repeated treatments with psychostimulant drugs generate behavioral sensitization.
      In the present study we employed a paired/unpaired protocol to assess the effects
      of repeated apomorphine (2.0 mg/kg) treatments upon locomotion behavior. In the
      first experiment we assessed the effects of conditioning upon apomorphine
      sensitization. Neither the extinction of the conditioned response nor a counter
      conditioning procedure in which we paired an inhibitory treatment (apomorphine
      0.05 mg/kg) with the previously established conditioned stimulus modified the
      sensitization response. In the second experiment, we administered the
      paired/unpaired protocol in two phases. In the second phase, we reversed the
      paired/unpaired protocol. Following the first phase, the paired group alone
      exhibited conditioned locomotion in the vehicle test and a sensitization
      response. In the second phase, the initial unpaired group which received 5 paired
      apomorphine trials during the reversal phase did not develop a conditioned
      response but developed a potentiated sensitization response. This disassociation
      of the conditioned response from the sensitization response is attributed to an
      apomorphine anti-habituation effect that can generate a false positive Pavlovian
      conditioned response effect. The potentiated sensitization response induced by
      the treatment reversal protocol points to an important role for the sequential
      experience of the paired/unpaired protocol in behavioral sensitization.

PMID- 20670920
TI  - Association of genetic variation in cystathionine-beta-synthase and arsenic
      metabolism.
AB  - Variation in individual susceptibility to arsenic-induced disease may be
      partially explained by genetic differences in arsenic metabolism. Mounting
      epidemiological evidence and in vitro studies suggest that methylated arsenic
      metabolites, particularly monomethylarsonic (MMA3), are more acutely toxic than
      inorganic arsenic; thus, MMA3 may be the primary toxic arsenic species. To test
      the role of genetic variation in arsenic metabolism, polymorphisms in genes
      involved in one-carbon metabolism [methylenetetrahydrofolate reductase (MTHFR),
      methionine synthase (MTR), cystathionine-beta-synthase (CBS), thymidylate
      synthase (TYMS), dihydrofolate reductase (DHFR), serine hydroxymethyltransferase
      1 (SHMT1)] and glutathione biosynthesis [glutathione-S-transferase omega 1
      (GSTO1)] were examined in an arsenic-exposed population to determine their
      influence in urinary arsenic metabolite patterns. In 142 subjects in Cordoba
      Province, Argentina, variant genotypes for CBS rs234709 and rs4920037 SNPs
      compared with wild-type homozygotes were associated with 24% and 26% increases,
      respectively, in the mean proportion of arsenic excreted as monomethylarsonic
      acid (%MMA). This difference is within the range of differences in %MMA seen
      between people with arsenic-related disease and those without such disease in
      other studies. Small inverse associations with CBS rs234709 and rs4920037
      variants were also found for the mean levels of the proportion of arsenic
      excreted as dimethylarsinous acid (%DMA). No other genetic associations were
      found. These findings are the first to suggest that CBS polymorphisms may
      influence arsenic metabolism in humans and susceptibility to arsenic-related
      disease.

PMID- 20670921
TI  - A phase II trial of dose-dense neoadjuvant gemcitabine, epirubicin, and albumin
      bound paclitaxel with pegfilgrastim in the treatment of patients with locally
      advanced breast cancer.
AB  - BACKGROUND: Neoadjuvant anthracycline/taxane combinations, with or without
      gemcitabine, produce pathologic complete responses (pCRs) in 15%-25% of patients.
      In this multicenter phase II study, we attempted to increase efficacy and
      decrease toxicity of a 3-drug gemcitabine-containing neoadjuvant regimen by
      administering dose-dense therapy with pegfilgrastim, and including albumin-bound
      paclitaxel as the taxane. PATIENTS AND METHODS: A total of 123 patients with
      locally advanced breast cancer were enrolled. Patients were treated with 6 doses
      of neoadjuvant gemcitabine 2000 mg/m2, epirubicin 50 mg/m2, and albumin-bound
      paclitaxel 175 mg/m2 intravenously administered at 14-day intervals. Following
      neoadjuvant chemotherapy, patients underwent either mastectomy or breast
      conservation surgery; pathologic response to treatment was assessed.
      Postoperatively, patients received 4 doses of gemcitabine 2000 mg/m2 with albumin
      bound paclitaxel 220 mg/m2 at 14-day intervals. Pegfilgrastim 6 mg was
      administered subcutaneously on day 2 following each dose of chemotherapy.
      RESULTS: A total of 116 patients (95%) completed neoadjuvant chemotherapy and had
      subsequent surgical resection. Twenty-three patients (20%) had a pCR. The
      estimated 3-year progression-free survival (PFS) and overall survival rates were
      48% and 86%, respectively. Neoadjuvant treatment was well tolerated; only 11% of
      the patients had grade 3/4 neutropenia, with 1 episode of neutropenic fever.
      Other grade 3/4 toxicities occurred in < 10% of the patients. CONCLUSION:
      Neoadjuvant biweekly chemotherapy with gemcitabine/epirubicin/albumin-bound
      paclitaxel with pegfilgrastim is feasible and well tolerated. The pCR rate of 20%
      and the 3-year PFS rate of 48% are similar to results achieved with other
      commonly used neoadjuvant regimens.

PMID- 20670922
TI  - Catcher in the Rye: J. D. Salinger dead at age 91.

PMID- 20670923
TI  - Rape myth beliefs and bystander attitudes among incoming college students.
AB  - OBJECTIVE: The bystander approach to rape prevention is gaining popularity on
      college campuses, although research is limited. This study explored bystander
      attitudes and their relationship with rape myths in a sample of college students.
      PARTICIPANTS: Surveys from 2,338 incoming undergraduate students at a large,
      northeastern university were analyzed. METHODS: Participants completed revised
      versions of the Illinois Rape Myth Acceptance Scale and the Bystander Attitude
      Scale. RESULTS: A higher acceptance of rape myths was reported by males, those
      pledging a fraternity/sorority, athletes, those without previous rape education,
      and those who did not know someone sexually assaulted. A greater willingness to
      intervene as a bystander was reported by females, those who had previous rape
      education, and those who knew someone sexually assaulted. Acceptance of rape
      myths was negatively related to willingness to intervene. CONCLUSIONS: Bystander
      intervention programs should include content on rape myths as well as focus on
      the role of gender.

PMID- 20670924
TI  - Exposing college students to exercise: the Training Interventions and Genetics of
      Exercise Response (TIGER) study.
AB  - OBJECTIVE: The Training Interventions and Genetics of Exercise Response (TIGER)
      study is an exercise program designed to introduce sedentary college students to
      regular physical activity and to identify genetic factors that influence response
      to exercise. PARTICIPANTS: A multiracial/ethnic cohort (N = 1,567; 39% male), age
      18 to 35 years, participated in the study. METHODS: Subjects underwent 30 weeks
      of exercise training, 3 days/week, for 40 minutes at 65% to 85% of age- and
      gender-predicted maximum heart rate reserve. Multiple measures of body
      size/composition, heart rate, and blood pressure were obtained. RESULTS: A total
      of 1,567 participants, (39% male), age 18 to 35 years, participated in the TIGER
      study. The prevalence of overweight/obesity in participants was 48.0%/19.3% in
      non-Hispanic Whites, 55.3%/24.2% in Hispanic Whites, 54.9%/25.4% in African
      Americans, and 38.3%/11.3% in Asians. Average within-semester retention was 68%,
      but overall retention (30 weeks, 2 semesters) was 20%. CONCLUSIONS: The TIGER
      study represents an efficacious strategy for introducing college-aged individuals
      to regular aerobic exercise.

PMID- 20670926
TI  - The bicycle helmet attitudes scale: using the health belief model to predict
      helmet use among undergraduates.
AB  - OBJECTIVE: This study examined bicycle helmet attitudes and practices of college
      undergraduates and developed the Bicycle Helmet Attitudes Scale, which was guided
      by the Health Belief Model (HBM; Rosenstock, 1974, in Becker MH, ed. The Health
      Belief Model and Personal Health Behavior. Thorofare, NJ: Charles B. Slack;
      1974:328-335) to predict reported helmet use. PARTICIPANTS: Students (N = 337)
      from a mid-sized university in the southeast completed a survey between November
      2006 and November 2007. METHODS: Participants completed a comprehensive survey on
      attitudes and behaviors relevant to bicycle helmet use. RESULTS: The resulting
      Bicycle Helmet Attitudes Scale contains 57 items and represents 10 reliable
      subscales that reflect the HBM. Only 12% of students were self-reported helmet
      users. Bicycle Helmet Attitudes Scale scores captured 52% of the variance
      associated with helmet use; each subscale differentiated wearers from nonwearers.
      Men reported more media influences than did women. CONCLUSIONS: The utility of
      the HBM to predicted bicycle helmet use was supported. Implications for promoting
      cycling safety are discussed.

PMID- 20670925
TI  - Turning 21 and the associated changes in drinking and driving after drinking
      among college students.
AB  - OBJECTIVE: The authors examined drinking and driving after drinking before and
      after turning 21. PARTICIPANTS: Participants were drawn from first time college
      students who were taking part in a 4-year longitudinal study of alcohol use and
      behavioral risks. METHODS: Web-based longitudinal surveys collected data on
      drinking and driving after drinking from August 2004 through November 2007 (n =
      1,817). A subset of participants (n = 224) also monitored their daily behavior
      during the month they turned 21 (January through May, 2007). RESULTS: Typical
      frequency and quantity of alcohol use increased from ages 18 to 21 years, whereas
      quantity decreased between 21 and 23 years of age. Driving after drinking showed
      a 72% relative increase (6% absolute increase) in the 2 weeks after turning 21.
      CONCLUSIONS: Reaching the legal drinking age is associated with decreases in the
      amount of alcohol consumed per drinking occasion, but an increase in driving
      after drinking.

PMID- 20670927
TI  - Prevalence of hepatitis B surface antigen in US-born and foreign-born
      Asian/Pacific Islander college students.
AB  - The prevalence of chronic hepatitis B (HBV) among college-age US-born Asian and
      Pacific Islanders (A/PI) is not well known. OBJECTIVES: To compare the prevalence
      of hepatitis B surface antigen (HBsAg) seropositivity in US-born to A/PI-born
      students at a public university. PARTICIPANTS: Undergraduate who self-identified
      themselves as A/PI. RESULTS: Of 145 US-born A/PI, 1.4% (confidence interval [CI]
      = 0.0%, 3.3%) tested positive for HBsAg compared to 3.3% (CI = 0.5%, 6.1%) of the
      152 A/PI-born students. Approximately 1/3 of all students were unaware of their
      HBV vaccination status. CONCLUSIONS: HBsAg prevalence among A/PI undergraduates,
      including US-born, is considerably higher (3 to 11 times) than the mainstream US
      population (0.3% to 0.5%) and supports the Centers for Disease Control and
      Prevention (CDC) recommendations for testing all persons of A/PI ancestry,
      including US-born persons whose parents were born in regions with HBsAg
      prevalence of >or=8%. Awareness of HBV vaccination status was relatively low and
      vaccination did not assure that individuals were HBsAg negative.

PMID- 20670928
TI  - Perceptions of body weight, weight management strategies, and depressive symptoms
      among US college students.
AB  - OBJECTIVE: To determine if inaccurate body weight perception predicts unhealthy
      weight management strategies and to determine the extent to which inaccurate body
      weight perception is associated with depressive symptoms among US college
      students. PARTICIPANTS: Randomly selected male and female college students in the
      United States (N = 97,357). METHODS: Data were from the 2006 National College
      Health Assessment. Analyses were conducted on students' body weight perceptions,
      weight loss strategies, and feelings of depression. RESULTS: Females with an
      inflated body weight perception were significantly more likely to engage in
      unhealthy weight management strategies and report depressive symptoms than were
      females with an accurate body weight perception. CONCLUSIONS: College women are
      concerned with weight and will take action to lose weight. Colleges may need to
      focus more on interventions targeting both diet and physical activity while also
      promoting positive body image.

PMID- 20670929
TI  - Overweight and obesity in lesbian and bisexual college women.
AB  - OBJECTIVE: To estimate and compare the prevalence of overweight and obesity among
      self-identified lesbian, bisexual, and heterosexual college age women. METHODS: A
      secondary analysis of the Spring 2006 National College Health Assessment was
      conducted with 31,500 female college students (aged 18 to 25 years) to compare
      body mass index (calculated from self-reported height and weight) among lesbian,
      bisexual and heterosexual college women. RESULTS: Compared to heterosexuals
      female college students, lesbians and bisexual women were both significantly more
      likely to be overweight or obese. Lesbians were also less likely to be
      underweight compared to heterosexual college women. CONCLUSIONS: Self-identified
      lesbian and bisexual college women were more likely to be overweight or obese
      than their heterosexual counterparts. Health care professionals and educators
      should target these high-risk populations for obesity prevention programs. This
      study highlights the need for additional research examining the potential risk
      factors for overweight and obesity among young sexual minority women.

PMID- 20670931
TI  - General statement of ethical principles and guidelines.
AB  - ACHA recognizes that these guidelines are a work in progress and will change as
      law and professional standards in the field of college health evolve. At this
      time, ACHA expects that all members actively uphold the principles and guidelines
      detailed in this document, as guides for conduct in professional activities and
      situations when breaches in these practices are evident.

PMID- 20670932
TI  - Response of IMCD3 cells to hypertonic challenges as analyzed by electron
      microscopy.
AB  - This work defines the ultrastructural responses of immortalized cells from the
      inner medullary collecting duct cells (IMCD3 cells) to hypertonic challenges. The
      cultured cells were either acutely exposed to hypertonic medium (550 mOsm/kgH2O)
      for 24-72 h or gradually adapted to 600 or 900 mOsm/kgH2O media with sodium
      chloride. After short (24 h) hypertonic challenges, there was an expansion of the
      Golgi apparatus with distinct expression of the gamma subunit of Na,K-ATPase. The
      frequency of active caspase-3-positive cells was unchanged as was also the
      measured activity of caspase-3. Immunoelectron microscopy showed that active
      caspase-3 in the positive cells was localized in cytoplasmic bodies 0.5-1 MUm in
      diameter but not in other structures. Apoptotic bodies with the nuclei were only
      rarely observed following acute hypertonicity for 24 to 72 h. Following prolonged
      hypertonic challenges, some cells showed condensation of the chromatin but still
      few apoptotic bodies. Gradual hypertonicity to 900 mOsm/kgH2O led to a decrease
      of microvilli, dilated cisternae of the endoplasmic reticulum (ER), increased
      abundance of free ribosomes and longitudinal mitochondrial cristae. Virus
      particles were present inside and outside the cells in all experimental
      conditions and appeared unrelated to the apoptotic process. The results suggest
      that cultured IMCD3 cells are resistant to short hypertonic challenge or gradual
      adaptation to moderate hypertonicity and only rarely exhibit more ultrastructural
      apoptotic changes than control cells. The presence of caspase-3-containing bodies
      is a novel finding, and we suggest that they arise from the ER and are involved
      in the apoptotic signaling system.

PMID- 20670933
TI  - Determination of the substrate specificity of protein-tyrosine phosphatase TULA-2
      and identification of Syk as a TULA-2 substrate.
AB  - TULA-1 (UBASH3A/STS-2) and TULA-2 (p70/STS-1) represent a novel class of protein
      tyrosine phosphatases. Previous studies suggest that TULA-2 is sequence-selective
      toward phosphotyrosyl (Tyr(P)) peptides. In this work the substrate specificity
      of TULA-1 and -2 was systematically evaluated by screening a combinatorial Tyr(P)
      peptide library. Although TULA-1 showed no detectable activity toward any of the
      Tyr(P) peptides in the library, TULA-2 recognizes two distinct classes of Tyr(P)
      substrates. On the N-terminal side of Tyr(P), the class I substrates contain a
      proline at the Tyr(P)-1 position, a hydrophilic residue at the Tyr(P)-2 position,
      and aromatic hydrophobic residues at positions Tyr(P)-3 and beyond. The class II
      substrates typically contain two or more acidic residues, especially at Tyr(P)-1
      to Tyr(P)-3 positions, and aromatic hydrophobic residues at other positions. At
      the C-terminal side of Tyr(P), TULA-2 generally prefers acidic and aromatic
      residues. The library screening results were confirmed by kinetic analysis of
      representative peptides selected from the library as well as Tyr(P) peptides
      derived from various Tyr(P) proteins. TULA-2 is highly active toward peptides
      corresponding to the Tyr(P)-323 and Tyr(P)-352 sites of Syk, and the Tyr(P)-397
      site of focal adhesion kinase and has lower activity toward other Tyr(P) sites in
      these proteins. In glycoprotein VI-stimulated platelets, knock-out of the TULA-2
      gene significantly increased the phosphorylation level of Syk at Tyr-323 and Tyr
      352 sites and to a lesser degree at the Tyr-525/526 sites. These results suggest
      that Syk is a bona fide TULA-2 substrate in platelets.

PMID- 20670934
TI  - Specificity in computational protein design.
AB  - A long-standing goal of computational protein design is to create proteins
      similar to those found in Nature. One motivation is to harness the exquisite
      functional capabilities of proteins for our own purposes. The extent of
      similarity between designed and natural proteins also reports on how faithfully
      our models represent the selective pressures that determine protein sequences. As
      the field of protein design shifts emphasis from reproducing native-like protein
      structure to function, it has become important that these models treat the notion
      of specificity in molecular interactions. Although specificity may, in some
      cases, be achieved by optimization of a desired protein in isolation, methods
      have been developed to address directly the desire for proteins that exhibit
      specific functions and interactions.

PMID- 20670935
TI  - The reciprocal regulation of gamma-synuclein and IGF-I receptor expression
      creates a circuit that modulates IGF-I signaling.
AB  - Insulin-like growth factor (IGF) system plays important roles in carcinogenesis
      and maintenance of the malignant phenotype. Signaling through the IGF-I receptor
      (IGF-IR) has been shown to stimulate the growth and motility of a wide range of
      cancer cells. gamma-synuclein (SNCG) is primarily expressed in peripheral neurons
      but also overexpressed in various cancer cells. Overexpression of SNCG correlates
      with tumor progression. In the present study we demonstrated a reciprocal
      regulation of IGF-I signaling and SNCG expression. IGF-I induced SNCG expression
      in various cancer cells. IGF-IR knockdown or IGF-IR inhibitor repressed SNCG
      expression. Both phosphatidylinositol 3-kinase and mitogen-activated protein
      kinase were involved in IGF-I induction of SNCG expression. Interestingly, SNCG
      knockdown led to proteasomal degradation of IGF-IR, thereby decreasing the steady
      state levels of IGF-IR. Silencing of SNCG resulted in a decrease in ligand
      induced phosphorylation of IGF-IR and its downstream signaling components,
      including insulin receptor substrate (IRS), Akt, and ERK1/2. Strikingly, SNCG
      physically interacted with IGF-IR and IRS-2. Silencing of IRS-2 impaired the
      interaction between SNCG and IGF-IR. Finally, SNCG knockdown suppressed IGF-I
      induced cell proliferation and migration. These data reveal that SNCG and IGF-IR
      are mutually regulated by each other. SNCG blockade may suppress IGF-I-induced
      cell proliferation and migration. Conversely, IGF-IR inhibitors may be of utility
      in suppressing the aberrant expression of SNCG in cancer cells and thereby block
      its pro-tumor effects.

PMID- 20670936
TI  - Generation of induced pluripotent stem cells in rabbits: potential experimental
      models for human regenerative medicine.
AB  - Human induced pluripotent stem (iPS) cells have the potential to establish a new
      field of promising regenerative medicine. Therefore, the safety and the
      efficiency of iPS-derived cells must be tested rigorously using appropriate
      animal models before human trials can commence. Here, we report the establishment
      of rabbit iPS cells as the first human-type iPS cells generated from a small
      laboratory animal species. Using lentiviral vectors, four human reprogramming
      genes (c-MYC, KLF4, SOX2, and OCT3/4) were introduced successfully into adult
      rabbit liver and stomach cells. The resulting rabbit iPS cells closely resembled
      human iPS cells; they formed flattened colonies with sharp edges and proliferated
      indefinitely in the presence of basic FGF. They expressed the endogenous
      pluripotency markers c-MYC, KLF4, SOX2, OCT3/4, and NANOG, whereas the introduced
      human genes were completely silenced. Using in vitro differentiating conditions,
      rabbit iPS cells readily differentiated into ectoderm, mesoderm, and endoderm.
      They also formed teratomas containing a variety of tissues of all three germ
      layers in immunodeficient mice. Thus, the rabbit iPS cells fulfilled all of the
      requirements for the acquisition of the fully reprogrammed state, showing high
      similarity to their embryonic stem cell counterparts we generated recently.
      However, their global gene expression analysis revealed a slight but rigid
      difference between these two types of rabbit pluripotent stem cells. The rabbit
      model should enable us to compare iPS cells and embryonic stem cells under the
      same standardized conditions in evaluating their ultimate feasibility for
      pluripotent cell-based regenerative medicine in humans.

PMID- 20670937
TI  - GATA switches as developmental drivers.
AB  - Transcriptional networks orchestrate complex developmental processes. Such
      networks are commonly instigated by master regulators of development.
      Considerable progress has been made in elucidating GATA factor-dependent genetic
      networks that control blood cell development. GATA-2 is required for the genesis
      and/or function of hematopoietic stem cells, whereas GATA-1 drives the
      differentiation of hematopoietic progenitors into a subset of the blood cell
      lineages. GATA-1 directly represses Gata2 transcription, and this involves GATA-1
      mediated displacement of GATA-2 from chromatin, a process termed a GATA switch.
      GATA switches occur at numerous loci with critical functions, indicating that
      they are widely utilized developmental control tools.

PMID- 20670938
TI  - Mechanism of hyperinsulinism in short-chain 3-hydroxyacyl-CoA dehydrogenase
      deficiency involves activation of glutamate dehydrogenase.
AB  - The mechanism of insulin dysregulation in children with hyperinsulinism
      associated with inactivating mutations of short-chain 3-hydroxyacyl-CoA
      dehydrogenase (SCHAD) was examined in mice with a knock-out of the hadh gene
      (hadh(-/-)). The hadh(-/-) mice had reduced levels of plasma glucose and elevated
      plasma insulin levels, similar to children with SCHAD deficiency. hadh(-/-) mice
      were hypersensitive to oral amino acid with decrease of glucose level and
      elevation of insulin. Hypersensitivity to oral amino acid in hadh(-/-) mice can
      be explained by abnormal insulin responses to a physiological mixture of amino
      acids and increased sensitivity to leucine stimulation in isolated perifused
      islets. Measurement of cytosolic calcium showed normal basal levels and abnormal
      responses to amino acids in hadh(-/-) islets. Leucine, glutamine, and alanine are
      responsible for amino acid hypersensitivity in islets. hadh(-/-) islets have
      lower intracellular glutamate and aspartate levels, and this decrease can be
      prevented by high glucose. hadh(-/-) islets also have increased [U
      (14)C]glutamine oxidation. In contrast, hadh(-/-) mice have similar glucose
      tolerance and insulin sensitivity compared with controls. Perifused hadh(-/-)
      islets showed no differences from controls in response to glucose-stimulated
      insulin secretion, even with addition of either a medium-chain fatty acid
      (octanoate) or a long-chain fatty acid (palmitate). Pull-down experiments with
      SCHAD, anti-SCHAD, or anti-GDH antibodies showed protein-protein interactions
      between SCHAD and GDH. GDH enzyme kinetics of hadh(-/-) islets showed an increase
      in GDH affinity for its substrate, alpha-ketoglutarate. These studies indicate
      that SCHAD deficiency causes hyperinsulinism by activation of GDH via loss of
      inhibitory regulation of GDH by SCHAD.

PMID- 20670939
TI  - Modulation of integrin activation by an entropic spring in the {beta}-knee.
AB  - We show that the length of a loop in the beta-knee, between the first and second
      cysteines (C1-C2) in integrin EGF-like (I-EGF) domain 2, modulates integrin
      activation. Three independent sets of mutants, including swaps among different
      integrin beta-subunits, show that C1-C2 loop lengths of 12 and longer favor the
      low affinity state and masking of ligand-induced binding site (LIBS) epitopes.
      Shortening length from 12 to 4 residues progressively increases ligand binding
      and LIBS epitope exposure. Compared with length, the loop sequence had a smaller
      effect, which was ascribable to stabilizing loop conformation, and not
      interactions with the alpha-subunit. The data together with structural
      calculations support the concept that the C1-C2 loop is an entropic spring and an
      emerging theme that disordered regions can regulate allostery. Diversity in the
      length of this loop may have evolved among integrin beta-subunits to adjust the
      equilibrium between the bent and extended conformations at different set points.

PMID- 20670940
TI  - Characterization of the prion protein in human urine.
AB  - The presence of the prion protein (PrP) in normal human urine is controversial
      and currently inconclusive. This issue has taken a special relevance because
      prion infectivity has been demonstrated in urine of animals carrying experimental
      or naturally occurring prion diseases, but the actual presence and tissue origin
      of the infectious prion have not been determined. We used immunoprecipitation,
      one- and two-dimensional electrophoresis, and mass spectrometry to prove
      definitely the presence of PrP in human urine and its post-translational
      modifications. We show that urinary PrP (uPrP) is truncated mainly at residue 112
      but also at other residues up to 122. This truncation makes uPrP undetectable
      with some commonly used antibodies to PrP. uPrP is glycosylated and carries an
      anchor which, at variance with that of cellular PrP, lacks the inositol
      associated phospholipid moiety, indicating that uPrP is probably shed from the
      cell surface. The detailed characterization of uPrP reported here definitely
      proves the presence of PrP in human urine and will help determine the origin of
      prion infectivity in urine.

PMID- 20670941
TI  - Aggregated electronegative low density lipoprotein in human plasma shows a high
      tendency toward phospholipolysis and particle fusion.
AB  - Aggregation and fusion of lipoproteins trigger subendothelial retention of
      cholesterol, promoting atherosclerosis. The tendency of a lipoprotein to form
      fused particles is considered to be related to its atherogenic potential. We
      aimed to isolate and characterize aggregated and nonaggregated subfractions of
      LDL from human plasma, paying special attention to particle fusion mechanisms.
      Aggregated LDL was almost exclusively found in electronegative LDL (LDL(-)), a
      minor modified LDL subfraction, but not in native LDL (LDL(+)). The main
      difference between aggregated (agLDL(-)) and nonaggregated LDL(-) (nagLDL(-)) was
      a 6-fold increased phospholipase C-like activity in agLDL(-). agLDL(-) promoted
      the aggregation of LDL(+) and nagLDL(-). Lipoprotein fusion induced by alpha
      chymotrypsin proteolysis was monitored by NMR and visualized by transmission
      electron microscopy. Particle fusion kinetics was much faster in agLDL(-) than in
      nagLDL(-) or LDL(+). NMR and chromatographic analysis revealed a rapid and
      massive phospholipid degradation in agLDL(-) but not in nagLDL(-) or LDL(+).
      Choline-containing phospholipids were extensively degraded, and ceramide,
      diacylglycerol, monoacylglycerol, and phosphorylcholine were the main products
      generated, suggesting the involvement of phospholipase C-like activity. The
      properties of agLDL(-) suggest that this subfraction plays a major role in
      atherogenesis by triggering lipoprotein fusion and cholesterol accumulation in
      the arterial wall.

PMID- 20670942
TI  - Rab32 modulates apoptosis onset and mitochondria-associated membrane (MAM)
      properties.
AB  - The mitochondria-associated membrane (MAM) has emerged as an endoplasmic
      reticulum (ER) signaling hub that accommodates ER chaperones, including the
      lectin calnexin. At the MAM, these chaperones control ER homeostasis but also
      play a role in the onset of ER stress-mediated apoptosis, likely through the
      modulation of ER calcium signaling. These opposing roles of MAM-localized
      chaperones suggest the existence of mechanisms that regulate the composition and
      the properties of ER membrane domains. Our results now show that the GTPase Rab32
      localizes to the ER and mitochondria, and we identify this protein as a regulator
      of MAM properties. Consistent with such a role, Rab32 modulates ER calcium
      handling and disrupts the specific enrichment of calnexin on the MAM, while not
      affecting the ER distribution of protein-disulfide isomerase and mitofusin-2.
      Furthermore, Rab32 determines the targeting of PKA to mitochondrial and ER
      membranes and through its overexpression or inactivation increases the
      phosphorylation of Bad and of Drp1. Through a combination of its functions as a
      PKA-anchoring protein and a regulator of MAM properties, the activity and
      expression level of Rab32 determine the speed of apoptosis onset.

PMID- 20670943
TI  - Expression of receptors for luteinizing hormone-releasing hormone (LH-RH) in
      prostate cancers following therapy with LH-RH agonists.
AB  - PURPOSE: In addition to their expression on pituitary cells, receptors for
      luteinizing hormone-releasing hormone (LH-RH) are found on most prostate cancer
      cells. These tumoral LH-RH receptors mediate the direct cytotoxic effects of LH
      RH analogs and are potential therapeutic targets. Although pituitary LH-RH
      receptors are downregulated following prolonged exposure to LH-RH agonists, there
      is no evidence that tumoral receptors behave in a similar manner. To better
      characterize expression of tumoral LH-RH receptors, specimens of prostate cancer
      from various cohorts of patients were analyzed. EXPERIMENTAL DESIGN: Surgical
      specimens were obtained from untreated patients with prostate cancer and from
      patients with metastatic castration-resistant prostate cancer previously treated
      with bilateral orchiectomy. To address the possibility of receptor
      downregulation, two additional cohorts of patients who had been previously
      treated with LH-RH agonists were included. One group received neoadjuvant therapy
      prior to prostatectomy, and the other group was treated for metastatic disease
      with LH-RH agonists and, at progression, required palliative resection of the
      prostate. Lymph node metastases from previously untreated patients were subjected
      to similar analysis. RESULTS: Expression of LH-RH receptors was found in most
      specimens. The relative expression of LH-RH receptor mRNA in untreated patients
      was greater in patients whose tumor had received a Gleason score <8. CONCLUSIONS:
      LH-RH receptor expression persisted despite prolonged exposure to LH-RH agonists.
      These findings support the concept of targeting cytotoxic LH-RH analogs to
      prostatic LH-RH receptors, using these receptors to gain entry into cancer cells
      to deliver a hybridized cytotoxic moiety for the treatment of prostate cancer.

PMID- 20670944
TI  - Molecular analysis of non-small cell lung cancer identifies subsets with
      different sensitivity to insulin-like growth factor I receptor inhibition.
AB  - PURPOSE: This study aimed to identify molecular determinants of sensitivity of
      non-small cell lung cancer (NSCLC) to anti-insulin-like growth factor receptor
      (IGF-IR) therapy. EXPERIMENTAL DESIGN: A total of 216 tumor samples were
      investigated, of which 165 consisted of retrospective analyses of banked tissue
      and an additional 51 were from patients enrolled in a phase II study of
      figitumumab, a monoclonal antibody against IGF-IR, in stage IIIb/IV NSCLC.
      Biomarkers assessed included IGF-IR, epidermal growth factor receptor, IGF-II,
      IGF-IIR, insulin receptor substrate 1 (IRS-1), IRS-2, vimentin, and E-cadherin.
      Subcellular localization of IRS-1 and phosphorylation levels of mitogen-activated
      protein kinase and Akt1 were also analyzed. RESULTS: IGF-IR was differentially
      expressed across histologic subtypes (P = 0.04), with highest levels observed in
      squamous cell tumors. Elevated IGF-IR expression was also observed in a small
      number of squamous cell tumors responding to chemotherapy combined with
      figitumumab (P = 0.008). Because no other biomarker/response interaction was
      observed using classical histologic subtyping, a molecular approach was
      undertaken to segment NSCLC into mechanism-based subpopulations. Principal
      component analysis and unsupervised Bayesian clustering identified three NSCLC
      subsets that resembled the steps of the epithelial to mesenchymal transition: E
      cadherin high/IRS-1 low (epithelial-like), E-cadherin intermediate/IRS-1 high
      (transitional), and E-cadherin low/IRS-1 low (mesenchymal-like). Several markers
      of the IGF-IR pathway were overexpressed in the transitional subset. Furthermore,
      a higher response rate to the combination of chemotherapy and figitumumab was
      observed in transitional tumors (71%) compared with those in the mesenchymal-like
      subset (32%; P = 0.03). Only one epithelial-like tumor was identified in the
      phase II study, suggesting that advanced NSCLC has undergone significant
      dedifferentiation at diagnosis. CONCLUSION: NSCLC comprises molecular subsets
      with differential sensitivity to IGF-IR inhibition.

PMID- 20670945
TI  - Assessment of vaccine-induced CD4 T cell responses to the 119-143 immunodominant
      region of the tumor-specific antigen NY-ESO-1 using DRB1*0101 tetramers.
AB  - PURPOSE: NY-ESO-1 (ESO), a tumor-specific antigen of the cancer/testis group, is
      presently viewed as an important model antigen for the development of generic
      anticancer vaccines. The ESO(119-143) region is immunodominant following
      immunization with a recombinant ESO vaccine. In this study, we generated
      DRB1*0101/ESO(119-143) tetramers and used them to assess CD4 T-cell responses in
      vaccinated patients expressing DRB1*0101 (DR1). EXPERIMENTAL DESIGN: We generated
      tetramers of DRB1*0101 incorporating peptide ESO(119-143) using a previously
      described strategy. We assessed ESO(119-143)-specific CD4 T cells in peptide
      stimulated postvaccine cultures using the tetramers. We isolated DR1/ESO(119-143)
      tetramer(+) cells by cell sorting and characterized them functionally. We
      assessed vaccine-induced CD4(+) DR1/ESO(119-143) tetramer(+) T cells ex vivo and
      characterized them phenotypically. RESULTS: Staining of cultures from vaccinated
      patients with DR1/ESO(119-143) tetramers identified vaccine-induced CD4 T cells.
      Tetramer(+) cells isolated by cell sorting were of T(H)1 type and efficiently
      recognized full-length ESO. We identified ESO(123-137) as the minimal optimal
      epitope recognized by DR1-restricted ESO-specific CD4 T cells. By assessing
      DR1/ESO(119-143) tetramer(+) cells using T cell receptor (TCR) beta chain
      variable region (Vbeta)-specific antibodies, we identified several frequently
      used Vbeta. Finally, direct ex vivo staining of patients' CD4 T cells with
      tetramers allowed the direct quantification and phenotyping of vaccine-induced
      ESO-specific CD4 T cells. CONCLUSIONS: The development of DR1/ESO(119-143)
      tetramers, allowing the direct visualization, isolation, and characterization of
      ESO-specific CD4 T cells, will be instrumental for the evaluation of spontaneous
      and vaccine-induced immune responses to this important tumor antigen in DR1
      expressing patients.

PMID- 20670946
TI  - Monoclonal antibodies to fibroblast growth factor receptor 2 effectively inhibit
      growth of gastric tumor xenografts.
AB  - PURPOSE: Overexpression of fibroblast growth factor receptor 2 (FGFR2) may be a
      causative factor of a number of human tumors, especially gastric tumors of the
      poorly differentiated type. We investigated whether monoclonal antibodies (mAbs)
      directed against FGFR2 can inhibit the growth of tumors in xenograft models.
      EXPERIMENTAL DESIGN: We generated and characterized 3 mAbs that recognize
      different epitopes on FGFR2: GAL-FR21, GAL-FR22, and GAL-FR23. The ability of the
      mAbs to recognize the FGFR2IIIb and FGFR2IIIc isoforms of FGFR2 was determined,
      as was their ability to block binding of FGF ligands to FGFR2. The capability of
      the mAbs to inhibit FGF-induced FGFR2 phosphorylation and to downmodulate FGFR2
      expression was also investigated. Finally, the ability of the anti-FGFR2 mAbs to
      inhibit tumor growth was determined by establishing xenografts of SNU-16 and OCUM
      2M human gastric tumor cell lines in nude mice, treating with each mAb (0.5-5
      mg/kg intraperitoneally twice weekly) and monitoring tumor size. RESULTS: Of the
      3 mAbs, GAL-FR21 binds only the FGFR2IIIb isoform, whereas GAL-FR22 and GAL-FR23
      bind to both the FGFR2IIIb and FGFR2IIIc forms, with binding regions respectively
      in the D3, D2-D3, and D1 domains of FGFR2. GAL-FR21 and GAL-FR22 blocked the
      binding of FGF2, FGF7 and FGF10 to FGFR2IIIb. GAL-FR21 inhibited FGF2 and FGF7
      induced phosphorylation of FGFR2, and both mAbs downmodulated FGFR2 expression on
      SNU-16 cells. These mAbs effectively inhibited growth of established SNU-16 and
      OCUM-2M xenografts in mice. CONCLUSIONS: Anti-FGFR2 mAbs GAL-FR21 and GAL-FR22
      have potential for the treatment of gastric and other tumors.

PMID- 20670948
TI  - Fluorescence resonance energy transfer biosensors for cancer detection and
      evaluation of drug efficacy.
AB  - A sensitive and specific fluorescence resonance energy transfer (FRET) biosensor
      was developed by Mizutani and colleagues and applied to detect the activity of
      BCR-ABL kinase in live cells. This biosensor allowed the detection of cancerous
      and drug-resistant cells, and the evaluation of kinase inhibitor efficacy. Future
      biosensor development and imaging can increasingly contribute to cancer diagnosis
      and therapeutics.

PMID- 20670949
TI  - Epithelial membrane protein-2 is a novel therapeutic target in ovarian cancer.
AB  - PURPOSE: The tetraspan protein epithelial membrane protein-2 (EMP2) has been
      shown to regulate the surface display and signaling from select integrin pairs,
      and it was recently identified as a prognostic biomarker in human endometrial
      cancer. In this study, we assessed the role of EMP2 in human ovarian cancer.
      EXPERIMENTAL DESIGN: We examined the expression of EMP2 within a population of
      women with ovarian cancer using tissue microarray assay technology. We evaluated
      the efficacy of EMP2-directed antibody therapy using a fully human recombinant
      bivalent antibody fragment (diabody) in vitro and ovarian cancer xenograft models
      in vivo. RESULTS: EMP2 was found to be highly expressed in >70% of serous and
      endometrioid ovarian tumors compared with nonmalignant ovarian epithelium using a
      human ovarian cancer tissue microarray. Using anti-EMP2 diabody, we evaluated the
      in vitro response of nine human ovarian cancer cell lines with detectable EMP2
      expression. Treatment of human ovarian cancer cell lines with anti-EMP2 diabodies
      induced cell death and retarded cell growth, and these response rates correlated
      with cellular EMP2 expression. We next assessed the effects of anti-EMP2
      diabodies in mice bearing xenografts from the ovarian endometrioid carcinoma cell
      line OVCAR5. Anti-EMP2 diabodies significantly suppressed tumor growth and
      induced cell death in OVCAR5 xenografts. CONCLUSIONS: These findings indicate
      that EMP2 is expressed in the majority of ovarian tumors and may be a feasible
      target in vivo.

PMID- 20670950
TI  - A novel FRET-based biosensor for the measurement of BCR-ABL activity and its
      response to drugs in living cells.
AB  - PURPOSE: To develop a novel diagnostic method for the assessment of drug efficacy
      in chronic myeloid leukemia (CML) patients individually, we generated a biosensor
      that enables the evaluation of BCR-ABL kinase activity in living cells using the
      principle of fluorescence resonance energy transfer (FRET). EXPERIMENTAL DESIGN:
      To develop FRET-based biosensors, we used CrkL, the most characteristic substrate
      of BCR-ABL, and designed a protein in which CrkL is sandwiched between Venus, a
      variant of YFP, and enhanced cyan fluorescent protein, so that CrkL
      intramolecular binding of the SH2 domain to phosphorylated tyrosine (Y207)
      increases FRET efficiency. After evaluation of the properties of this biosensor
      by comparison with established methods including Western blotting and flow
      cytometry, BCR-ABL activity and its response to drugs were examined in CML
      patient cells. RESULTS: After optimization, we obtained a biosensor that
      possesses higher sensitivity than that of established techniques with respect to
      measuring BCR-ABL activity and its suppression by imatinib. Thanks to its high
      sensitivity, this biosensor accurately gauges BCR-ABL activity in relatively
      small cell numbers and can also detect <1% minor drug-resistant populations
      within heterogeneous ones. We also noticed that this method enabled us to predict
      future onset of drug resistance as well as to monitor the disease status during
      imatinib therapy, using patient cells. CONCLUSION: In consideration of its quick
      and practical nature, this method is potentially a promising tool for the
      prediction of both current and future therapeutic responses in individual CML
      patients, which will be surely beneficial for both patients and clinicians.

PMID- 20670951
TI  - Phase I/II study of oncolytic HSV GM-CSF in combination with radiotherapy and
      cisplatin in untreated stage III/IV squamous cell cancer of the head and neck.
AB  - PURPOSE: This study sought to define the recommended dose of JS1/34.5-/47-/GM
      CSF, an oncolytic herpes simplex type-1 virus (HSV-1) encoding human granulocyte
      macrophage colony-stimulating factor (GM-CSF), for future studies in combination
      with chemoradiotherapy in patients with squamous cell cancer of the head and neck
      (SCCHN). EXPERIMENTAL DESIGN: Patients with stage III/IVA/IVB SCCHN received
      chemoradiotherapy (70 Gy/35 fractions with concomitant cisplatin 100 mg/m(2) on
      days 1, 22, and 43) and dose-escalating (10(6), 10(6), 10(6), 10(6) pfu/mL for
      cohort 1; 10(6), 10(7), 10(7), 10(7) for cohort 2; 10(6), 10(8), 10(8), 10(8) for
      cohort 3) JS1/34.5-/47-/GM-CSF by intratumoral injection on days 1, 22, 43, and
      64. Patients underwent neck dissection 6 to 10 weeks later. Primary end points
      were safety and recommended dose/schedule for future study. Secondary end points
      included antitumor activity (radiologic, pathologic). Relapse rates and survival
      were also monitored. RESULTS: Seventeen patients were treated without delays to
      chemoradiotherapy or dose-limiting toxicity. Fourteen patients (82.3%) showed
      tumor response by Response Evaluation Criteria in Solid Tumors, and pathologic
      complete remission was confirmed in 93% of patients at neck dissection. HSV was
      detected in injected and adjacent uninjected tumors at levels higher than the
      input dose, indicating viral replication. All patients were seropositive at the
      end of treatment. No patient developed locoregional recurrence, and disease
      specific survival was 82.4% at a median follow-up of 29 months (range, 19-40
      months). CONCLUSIONS: JS1/34.5-/47-/GM-CSF combined with cisplatin-based
      chemoradiotherapy is well tolerated in patients with SCCHN. The recommended phase
      II dose is 10(6), 10(8), 10(8), 10(8). Locoregional control was achieved in all
      patients, with a 76.5% relapse-free rate so far. Further study of this approach
      is warranted in locally advanced SCCHN.

PMID- 20670952
TI  - Adenovirus targeting to prostate-specific membrane antigen through virus
      displayed, semirandom peptide library screening.
AB  - The convergence of phage-displayed peptide libraries and recombinant viral
      vectors launched a promising new direction in targeted viral gene therapeutics,
      but the translation of targeting peptides to functional cancer therapeutic agents
      has been challenging. Here, we report progress in developing a successful
      strategy to optimize targeted viral infection through adenovirus-displayed,
      semirandom peptide libraries. A phage-derived peptide targeting the prostate
      specific membrane antigen (PSMA) was genetically incorporated into the adenoviral
      capsid Fiber protein and flanked by random peptide cassettes. The resulting
      adenovirus library was biopanned against PSMA-expressing cells and tumors to
      identify a PSMA-retargeted adenovirus. While the initial peptide alone could not
      target viral infection, the selected virus preferentially infects PSMA-expressing
      cells through the targeting peptide and infects LNCaP tumors after intravenous
      injection. Our results indicate that virus-displayed, semirandom peptide
      libraries can be used to optimize targeting infection. This approach represents a
      novel principle for developing targeted agents in a variety of disease models.

PMID- 20670954
TI  - The ITK-SYK fusion oncogene induces a T-cell lymphoproliferative disease in mice
      mimicking human disease.
AB  - Peripheral T-cell lymphomas (PTCL) constitute a major treatment problem with high
      mortality rates due to the minimal effectiveness of conventional chemotherapy.
      Recent findings identified ITK-SYK as the first recurrent translocation in 17% of
      unspecified PTCLs and showed the overexpression of SYK in more than 90% of PTCLs.
      Here, we show that the expression of ITK-SYK in the bone marrow of BALB/c mice
      causes a T-cell lymphoproliferative disease in all transplanted mice within 8
      weeks after transplantation. The disease was characterized by the infiltration of
      spleen, lymph nodes, bone marrow, and skin with CD3+CD4+CD8- and CD3+CD4-CD8- ITK
      SYK-positive T-cells accompanied by a systemic inflammatory reaction with
      upregulation of interleukin 5 and INF-gamma. ITK-SYK-positive T-cells showed
      enhanced apoptosis resistance and INF-gamma production in vitro. The disease was
      serially transplantable, inducing clonal T-cell expansion in secondary
      recipients. The action of ITK-SYK in vivo was dependent on SYK kinase activity
      and disease development could be inhibited by the treatment of mice with SYK
      inhibitors. Interestingly, the translocation of ITK-SYK from the membrane to the
      cytoplasm, using a point mutation in the pleckstrin homology domain (ITK-SYK
      R29C), did not abolish, but rather, enhanced disease development in transplanted
      mice. CBL binding was strongly enhanced in membrane-associated ITK-SYK E42K and
      was causative for delayed disease development. Our results show that ITK-SYK
      causes a T-cell lymphoproliferative disease in mice, supporting its role in T
      cell lymphoma development in humans. Therefore, pharmacologic inhibition of SYK
      in patients with U-PTCLs carrying the ITK-SYK fusion protein might be an
      effective treatment strategy.

PMID- 20670955
TI  - MET receptor sequence variants R970C and T992I lack transforming capacity.
AB  - High-throughput sequencing promises to accelerate the discovery of sequence
      variants, but distinguishing oncogenic mutations from irrelevant "passenger"
      mutations remains a major challenge. Here we present an analysis of two sequence
      variants of the MET receptor (hepatocyte growth factor receptor) R970C and T992I
      (also designated R988C and T1010I). Previous reports indicated that these
      sequence variants are transforming and contribute to oncogenesis. We screened
      patients with chronic lymphocytic leukemia (CLL), acute myeloid leukemia (AML),
      chronic myelomonocytic leukemia (CMML), colorectal cancer, endometrial cancer,
      thyroid cancer, or melanoma, as well as individuals without cancer, and found
      these variants at low frequencies in most cohorts, including normal individuals.
      No evidence of increased phosphorylation or transformative capacity by either
      sequence variant was found. Because small-molecule inhibitors for MET are
      currently in development, it will be important to distinguish between oncogenic
      sequence variants and rare single-nucleotide polymorphisms to avoid the use of
      unnecessary, and potentially toxic, cancer therapy agents.

PMID- 20670956
TI  - CIIA is a novel regulator of detachment-induced cell death.
AB  - Detachment-induced cell death, or anoikis, is a type of apoptosis that occurs
      when epithelial cells lose their attachment to the extracellular matrix. Anoikis
      serves as a physiologic barrier to metastasis. Deviation from the tightly
      regulated mechanism of detachment-induced cell death might result in progression
      to metastatic cancer. Here, we investigated the function of CIIA in the
      regulation of anoikis. CIIA protein was upregulated in colon cancer tissue
      samples. Knockdown of CIIA in metastatic colorectal carcinoma SW620 and KM12SM
      cells promoted detachment-induced cell death through the regulation of caspase
      activation. Knockdown of CIIA also inhibited anchorage-independent growth in soft
      agar and colony formation after suspension stress. These observations suggest
      that CIIA is a novel negative regulator of anoikis.

PMID- 20670957
TI  - Relationship between kidney function and risk of asymptomatic peripheral arterial
      disease in elderly subjects.
AB  - BACKGROUND: Limited data exist regarding the relationship between kidney function
      and incident asymptomatic peripheral arterial disease (PAD). METHODS: The study
      population consisted of 2881 participants of the Intervention Project on
      Cerebrovascular Diseases and Dementia in the Community of Ebersberg, Bavaria, a
      community-based cohort of elderly individuals. Kidney function was calculated as
      creatinine clearance (Ccr) estimated by the Cockcroft-Gault formula. Incident PAD
      was defined as a new onset of ankle-brachial index < 0.9 assessed at regular
      examinations among those with an ankle brachial pressure index (ABPI) >= 0.9 at
      baseline. Relative risks (RR) for PAD were compared across declining kidney
      function quartiles. RESULTS: Mean serum concentration of creatinine and Ccr were
      0.82 +/- 0.31 mg/dL and 78 +/- 21 mL/min/1.73 m(2). After 6 years of follow-up,
      478 (17%) participants developed incident asymptomatic PAD. After adjustment for
      demographic factors and cardiovascular risk factors, lower Ccr quartiles were
      directly associated with a higher risk of PAD. Compared with participants in
      quartile 1 (> 89 mL/min/1.73 m(2)), the adjusted RR (95% CI) for PAD were 1.01
      (0.88-1.19) for quartile 2 (75-89 mL/min/1.73 m(2)), 1.05 (0.93-1.23) for
      quartile 3 (64-75 mL/min/1.73 m(2)) and 1.10 (1.01-1.44) for quartile 4 (< 64
      mL/min/1.73 m(2); P = 0.009 for trend). Cardiovascular events as a function of
      baseline Ccr and incident PAD showed that most vascular events occurred in
      participants with Ccr < 60 mL/min/1.73 m(2) at baseline and incident PAD (log
      rank test, P = 0.0018). CONCLUSIONS: Lower kidney function is associated with
      incident asymptomatic PAD. In addition, the combination of impaired kidney
      function and incident PAD better predicts cardiovascular outcomes.

PMID- 20670958
TI  - Comparison of MMF efficacy and safety in paediatric vs. adult renal
      transplantation: subgroup analysis of the randomised, multicentre FDCC trial.
AB  - BACKGROUND: Mycophenolate mofetil (MMF) is widely used for immunosuppressive
      therapy in renal transplantation, but comparative data regarding efficacy and
      safety in paediatric vs. adult kidney allograft recipients in one and the same
      study are lacking. METHODS: We therefore performed this subgroup analysis of the
      FDCC trial, a 12-month, prospective, randomised study, comparing fixed-dose (FD)
      with concentration-controlled (CC) MMF dosing in paediatric and adult renal
      transplant recipients. Sixty-two paediatric and 839 adult de novo patients in 19
      countries were randomised 1:1 to receive fixed-dose or concentration-controlled
      MMF therapy in combination with calcineurin inhibitors and corticosteroids.
      RESULTS: Both patient and allograft survival proved to be excellent in paediatric
      patients (98.4% and 90.3%) and adults (96.8% and 95.0%). The rates of biopsy
      proven acute rejections (BPAR) and treated acute rejection episodes (ARE) were
      comparable between paediatric (12.9% and 17.7%) and adult patients (15.5% and
      20.7%). Transplant function at 12 months post-transplant was similar in
      paediatric (67.8 +/- 45.6 mL/min/1.73 m2;) and adult recipients (64.7 +/- 23.3
      mL/min/1.73 m2;). Children < 6 years (n = 10) exhibited a numerically higher
      frequency of leucocytopaenia (20%), diarrhoea (40%) and weight loss (10%) than
      older children (6-18 years; 5.8%, 28.8% and 1.9%) and adults (16.1%, 24.7% and
      1.5%). On the whole, the percentage of patients who experienced adverse events
      causing interruption of MMF therapy were numerically lower in children (4.8%)
      than in adults (12.5%). Conclusions. The overall efficacy and tolerability of MMF
      appear to be comparable between paediatric and adult patients. Further studies
      are needed to validate these results.

PMID- 20670959
TI  - Importance of dynamic dyssynchrony in the occurrence of hypertensive heart
      failure with normal ejection fraction.
AB  - AIMS: The impact of haemodynamic stress on left ventricular (LV) dyssynchrony in
      heart failure with normal ejection fraction (HFNEF) remains unknown. We sought to
      evaluate the relationship and predictive value of dynamic changes of LV
      dyssynchrony on hypertensive HFNEF. METHODS AND RESULTS: A total of 131 subjects
      including 47 hypertensive HFNEF patients, 34 hypertensive patients with left
      ventricular hypertrophy (LVH) without HFNEF, and 50 normal controls were studied
      by dobutamine stress echocardiography with tissue Doppler imaging. Systolic and
      diastolic dyssynchrony were assessed using the LV six-basal-six-mid-segment model
      and cut-off values were derived from normal controls. The mean basal segments
      longitudinal systolic (mean Sm) and early diastolic (mean Em) velocities were
      measured. In normal controls, systolic and diastolic dyssynchrony did not develop
      during stress. The prevalence of resting systolic (36.2% vs. 38.2%, P = 0.85) and
      diastolic (34.0% vs. 29.4%, P = 0.66) dyssynchrony was similar in HFNEF and LVH
      groups. During stress, the prevalence of systolic and diastolic dyssynchrony
      increased dramatically to 85.1% and 87.2%, respectively, in HFNEF group, but only
      52.9% and 58.8% in LVH group (P < 0.005). In HFNEF group, stress-induced increase
      in mean Sm was significantly blunted (2.8 +/- 2.0 vs. 4.2 +/- 2.4 cm/s, P =
      0.004), and the increase was abolished for mean Em (-0.3 +/- 2.5 vs. 2.4 +/- 3.4
      cm/s, P < 0.001). On multivariate analysis, stress-induced changes in mean Em (OR
      = 0.69, P = 0.004) and mean Sm (OR = 0.56, P = 0.004), and diastolic (OR = 4.6, P
      = 0.005) and systolic dyssynchrony during stress (OR = 4.3, P = 0.038) were
      independent determinants for occurrence of HFNEF. CONCLUSION: Dynamic
      dyssynchrony during stress and impaired myocardial longitudinal function reserve
      are characteristics of HFNEF.

PMID- 20670960
TI  - Total thyroidectomy performed with the Starion vessel sealing system versus the
      conventional technique: a prospective randomized trial.
AB  - Meticulous dissection and accurate hemostasis are required in thyroid surgery.
      The authors recently performed a number of thyroidectomies using a new device
      that combines heat and pressure for sealing and cutting tissue. A prospective
      randomized trial was conducted on 98 patients subjected to total thyroidectomy
      for benign disease: 49 patients (group A) with the Starion tissue welding system
      and 49 (group B) with the clamp-and-tie technique. The 2 groups were comparable
      in mean age, gender, thyroidal volume (20-60 mL), incision length (<35 mm), and
      pathology. The authors evaluated operative time, postoperative serum calcemia,
      dosage and length of postoperative calcium and vitamin D treatment, drainage
      volume, hospital stay, and complications. Student's t test was used for
      quantitative variables; for categorical variables, the chi(2) test or Fisher's
      exact test, as appropriate, was used. The mean operative time was 53.8 +/- 6.1
      minutes in group A and 63.2 +/- 8 minutes in group B (P < .0001). The difference
      in terms of postoperative calcemia was significant (group A: 8.35 +/- 0.39 mg/dL;
      group B: 8.08 +/- 0.39 mg/dL; P < .001). The duration of postoperative treatment
      with calcium and vitamin D was significantly different (group A: 4 days; group B:
      5 days; P < .039). No significant difference in terms of postoperative
      complications was found. The new system reduced operative time and the duration
      of postoperative hypocalcemia, and there was minimal tissue necrosis and thermal
      spread. The reduction in duration of postoperative calcium and vitamin D
      treatment is also an indication of improvement in quality of the treatment.

PMID- 20670961
TI  - Development of cancer cooperative groups in Japan.
AB  - Investigator-initiated clinical trials are essential for improving the standard
      of care for cancer patients, because pharmaceutical companies do not conduct
      trials that evaluate combination chemotherapy using drugs from different
      companies, surgery, radiotherapy or multimodal treatments. Government-sponsored
      cooperative groups have played a vital role in developing cancer therapeutics
      since the 1950s in the USA; however, the establishment of these groups in Japan
      did not take place until 30 years later. Methodological standards for multicenter
      cancer clinical trials were established in the 1980s by the National Cancer
      Institute and cooperative groups. The Japan Clinical Oncology Group, one of the
      largest cooperative groups in the country, was instituted in 1990. Its data
      center and operations office, formed during the 1990s, applied the standard
      methods of US cooperative groups. At present, the Japan Clinical Oncology Group
      consists of 14 subgroups, a Data Center, an Operations Office, nine standing
      committees and an Executive Committee represented by the Japan Clinical Oncology
      Group Chair. Quality control and quality assurance at the Japan Clinical Oncology
      Group, including regular central monitoring, statistical methods, interim
      analyses, adverse event reporting and site visit audit, have complied with
      international standards. Other cooperative groups have also been established in
      Japan since the 1980s; however, nobody figures out all of them. A project
      involving the restructuring of US cooperative groups has been ongoing since 2005.
      Learning from the success of this project will permit further progress of the
      cancer clinical trials enterprise in Japan.

PMID- 20670962
TI  - Stereotactic body radiation therapy for lung cancer: achievements and
      perspectives.
AB  - Stereotactic body radiation therapy is a new treatment modality where narrow
      beams from several directions focus on the target while sparing the adjacent
      normal tissues with high accuracy. This technique basically derived from that of
      radiosurgery for intracranial lesions allows us to deliver high dose to the
      target leading to high control of the tumor without causing significant
      cytotoxicities associated with the treatment. Early-stage non-small cell lung
      cancers are regarded as most appropriate malignancies for this modality and
      accordingly have most intensively been investigated. With many encouraging
      outcomes in retrospective studies, several prospective clinical trials have been
      started world-wide. Japan Clinical Oncology Group protocol 0403 is a phase II
      trial of stereotactic body radiation therapy for T1N0M0 non-small cell lung
      cancer including both inoperable and operable patients. The results for operable
      patients are to be disclosed this year after 3 years of follow-up. It is highly
      probable that stereotactic body radiation therapy can be a standard treatment
      modality for inoperable patients for early-stage non-small cell lung cancer. The
      role of stereotactic body radiation therapy for operable patients is expected to
      be clarified by the outcomes of coming clinical trials. Tremendous advance in
      stereotactic body radiation therapy is expected when four-dimensional radiation
      therapy coping with tumor movement is realized. Among several approaches, tumor
      tracking appears most ideal. The new image-guided radiotherapy system which has
      the capability of tumor tracking has been developed in Japan.

PMID- 20670963
TI  - Effect of a sequential education and monitoring programme on quality-of-life
      components in heart failure.
AB  - AIMS: Trials of disease management programmes (DMP) in heart failure (HF) have
      shown controversial results regarding quality of life. We hypothesized that a DMP
      applied over the long-term could produce different effects on each of the quality
      of-life components. METHODS AND RESULTS: We extended the prospective, randomized
      REMADHE Trial, which studied a DMP in HF patients. We analysed changes in
      Minnesota Living with Heart Failure Questionnaire components in 412 patients,
      60.5% male, age 50.2 +/- 11.4 years, left ventricular ejection fraction 34.7 +/-
      10.5%. During a mean follow-up of 3.6 +/- 2.2 years, 6.3% of patients underwent
      heart transplantation and 31.8% died. Global quality-of-life scores improved in
      the DMP intervention group, compared with controls, respectively: 57.5 +/- 3.1
      vs. 52.6 +/- 4.3 at baseline, 32.7 +/- 3.9 vs. 40.2 +/- 6.3 at 6 months, 31.9 +/-
      4.3 vs. 41.5 +/- 7.4 at 12 months, 26.8 +/- 3.1 vs. 47.0 +/- 5.3 at the final
      assessment; P < 0.01. Similarly, the physical component (23.7 +/- 1.4 vs. 21.1 +/
      2.2 at baseline, 16.2 +/- 2.9 vs. 18.0 +/- 3.3 at 6 months, 17.3 +/- 2.9 vs.
      23.1 +/- 5.7 at 12 months, 11.4 +/- 1.6 vs. 19.9 +/- 2.4 final; P < 0.01), the
      emotional component (13.2 +/- 1.0 vs. 12.1 +/- 1.4 at baseline, 11.7 +/- 2.7 vs.
      12.3 +/- 3.1 at 6 months, 12.4 +/- 2.9 vs. 16.8 +/- 5.9 at 12 months, 6.7 +/- 1.0
      vs. 10.6 +/- 1.4 final; P < 0.01) and the additional questions (20.8 +/- 1.2 vs.
      19.3 +/- 1.8 at baseline, 14.3 +/- 2.7 vs. 17.3 +/- 3.1 at 6 months, 12.4 +/- 2.9
      vs. 21.0 +/- 5.5 at 12 months, 6.7 +/- 1.4 vs. 17.3 +/- 2.2 final; P < 0.01) were
      better (lower) in the intervention group. The emotional component improved
      earlier than the others. Post-randomization quality of life was not associated
      with events. CONCLUSION: Components of the quality-of-life assessment responded
      differently to DMP. These results indicate the need for individualized DMP
      strategies in patients with HF. Trial registration information
      www.clincaltrials.gov NCT00505050-REMADHE.

PMID- 20670964
TI  - NICE public health guidance update.

PMID- 20670965
TI  - Estimating natural UV personal exposure with radiative transfer calculations.
AB  - The following study has investigated whether straightforward radiative transfer
      calculations can be used to adequately document natural UV personal exposure. The
      method was evaluated by comparing the results with erythemal doses accumulated by
      polysulphone films positioned on mannequins. The calculations succeeded in
      reproducing the variability associated with changing solar zenith angle and
      atmospheric conditions. A possible use of the model has been illustrated by
      estimating the daily exposure during 1 y of a hypothetical office worker,
      according to a simple occupational schedule. The calculated daily exposures
      indicated the importance of holiday periods in the risk of acute overexposure and
      in the total yearly dose.

PMID- 20670969
TI  - Meiosis initiation in the human ovary requires intrinsic retinoic acid synthesis.
AB  - BACKGROUND: The initiation of meiosis is crucial to fertility. While extensive
      studies in rodents have enhanced our understanding of this process, studies in
      human fetal ovary are lacking. METHODS: We used RT-PCR and immunohistochemistry
      to investigate expression of meiotic factors in human fetal ovaries from 6 to 15
      weeks post fertilization (wpf) and developed an organ culture model to study the
      initiation of human meiosis. RESULTS: We observed the first meiotic cells at 11
      wpf, when STRA8, SPO11 and DMC1 are first expressed. In culture, meiosis
      initiation is observed in 10 and 11 wpf ovaries and meiosis is maintained by
      addition of fetal calf serum. Meiosis is stimulated, compared with control, by
      retinoic acid (RA) (P < 0.05). No major change occurred in mRNA for CYP26B1, the
      RA-degrading enzyme proposed to control the timing of meiosis in mice. We did,
      however, observe increased mRNA levels for ALDH1A1 in human ovary when meiosis
      began, and evidence for a requirement to synthesize RA and thus sustain meiosis.
      Indeed, ALDH inhibition by citral prevented the appearance of meiotic cells.
      Finally, 8 wpf ovaries (and earlier stages) were unable to initiate meiosis
      whatever the length of culture, even in the presence of RA and serum. However,
      when human germ cells from 8 wpf ovaries were placed in a mouse ovarian
      environment, some did initiate meiosis. CONCLUSIONS: Our data indicate that
      meiosis initiation in the human ovary relies partially on RA, but that the
      progression and regulation of this process appears to differ in many aspects from
      that described in mice.

PMID- 20670971
TI  - The epidemic has gone global: can Exercise is Medicine help quell the tide?

PMID- 20670970
TI  - Disrupted functional brain connectivity during verbal working memory in children
      and adolescents with schizophrenia.
AB  - Children and adolescents who develop schizophrenia tend to have greater symptom
      severity than adults who develop the illness. Since the brain continues to mature
      into early adulthood, developmental differences in brain structure and function
      may provide clues to the underlying neurobiology of schizophrenia. With an
      emerging body of evidence supporting disrupted connectivity contributing to the
      underlying pathophysiology of schizophrenia, it was our goal to assess
      differences in functional connectivity in children and adolescents who develop
      schizophrenia. Participants included a total of 28 children and adolescents (14
      patients with schizophrenia and 14 age- and gender-matched controls). All
      subjects underwent a functional magnetic resonance imaging scan involving a
      modified Sternberg Item Recognition Paradigm with 3 working memory (WkM) loads.
      Patients had poorer performance at all 3 WkM loads without a load by diagnosis
      interaction. Functional imaging results demonstrated 3 specific brain networks
      disrupted in children and adolescents with schizophrenia. These networks include
      1) the anterior cingulate and the temporal lobes, bilaterally; 2) the cerebellum
      with subcortical regions; and 3) the occipital lobe and the cerebellum. Patients
      with early-onset schizophrenia demonstrate abnormal functional connectivity in
      networks involving limbic, temporal lobe, cerebellum, and early visual processing
      streams.

PMID- 20670972
TI  - A-Z of nutritional supplements: dietary supplements, sports nutrition foods and
      ergogenic aids for health and performance Part 11.

PMID- 20670973
TI  - Suicide and karoshi (death from overwork) during the recent economic crises in
      Japan: the impacts, mechanisms and political responses.

PMID- 20670975
TI  - Social relationships at work and depression.

PMID- 20670974
TI  - Inequality in provision of medical care in Sweden: a case of social
      epidemiological hypochondria?

PMID- 20670976
TI  - The SIN List as model for the identification of Substances of Very High Concern.

PMID- 20670977
TI  - Non-participant characteristics and the association between socioeconomic factors
      and brain tumour risk.
AB  - BACKGROUND: The aim of the study was to identify demographic and socioeconomic
      characteristics of participants and non-participants in a Swedish population
      based case-control study on brain tumours and to analyse the association between
      socioeconomic factors and glioma and meningioma risk. METHODS: Record linkage was
      made to an official register to gather information on socioeconomic status,
      income, education and demography for all participating and non-participating
      cases and controls. RESULTS: 494 glioma cases, 321 meningioma cases and 955
      controls were eligible and 74%, 85% and 70%, respectively, participated. Working
      status and income level were positively associated with participation among cases
      and controls. Among both cases and controls, being married, and having a high
      education were also associated with participation. Having a family income level
      in the highest quartile was associated with an increased glioma risk (OR 1.5, 95%
      CI 1.1 to 2.1). This risk increase diminished when only participating individuals
      were included in the analysis. Socioeconomic factors were not associated with
      meningioma risk. CONCLUSIONS: Non-participation, related to socioeconomic
      factors, is a potential source of bias in case-control studies that should be
      acknowledged; however, the effect was not large in the present study due to the
      fact that the level of participation was comparable between cases and controls
      and participation was similarly influenced by socioeconomic factors among cases
      and controls. The association between a high income level and an increased glioma
      risk and possible underlying factors needs to be explored further.

PMID- 20670978
TI  - Multicenter phase II trial of adjuvant therapy for resected pancreatic cancer
      using cisplatin, 5-fluorouracil, and interferon-alfa-2b-based chemoradiation:
      ACOSOG Trial Z05031.
AB  - BACKGROUND: The American College of Surgeons Oncology Group sought to confirm the
      efficacy of a novel interferon-based chemoradiation regimen in a multicenter
      phase II trial. PATIENTS AND METHODS: Patients with resected (R0/R1)
      adenocarcinoma of the pancreatic head were treated with adjuvant interferon-alfa
      2b (3 million units s.c. on days 1, 3, and 5 of each week for 5.5 weeks),
      cisplatin (30 mg/m(2) i.v. weekly for 6 weeks), and continuous infusion 5
      fluorouracil (5-FU; 175 mg.m(2)/day for 38 days) concurrently with external-beam
      radiation (50.4 Gy). Chemoradiation was followed by two 6-week courses of
      continuous infusion 5-FU (200 mg.m(2)/day). The primary study end point was 18
      month overall survival from protocol enrollment (OS18); an OS18 >=65% was
      considered a positive study outcome. RESULTS: Eighty-nine patients were enrolled.
      Eighty-four patients were assessable for toxicity. The all-cause grade >=3
      toxicity rate was 95% (80 patients) during therapy. No long-term toxicity or
      toxicity-related deaths were noted. At 36-month median follow-up, the OS18 was
      69% [95% confidence interval (CI) 60% to 80%]; the median disease-free survival
      and overall survival were 14.1 months (95% CI 11.0-20.1 months) and 25.4 months
      (95% CI 23.4-34.1 months), respectively. CONCLUSIONS: Notwithstanding promising
      multi-institutional efficacy results, further development of this regimen will
      require additional modifications to mitigate toxic effects.

PMID- 20670979
TI  - Cortical functional reorganization and its relationship with brain structural
      damage in patients with benign multiple sclerosis.
AB  - BACKGROUND: Patients with multiple sclerosis (MS) who have a favourable clinical
      status several years after disease onset are classified as 'benign'. In many
      cases brain tissue damage does not differ between benign MS and the 'classical'
      MS forms. OBJECTIVE: To assess whether the favourable clinical course in benign
      MS could be explained by the presence of an efficient functional cortical
      reorganization. METHOD: Twenty-five right-handed patients with benign MS (defined
      as having Expanded Disability Status Scale <= 3 and disease duration >15 years)
      underwent functional MRI during a simple motor task (right-hand tapping) to
      assess movement-associated brain activation. This was compared with that of 10
      patients with relapsing-remitting MS and 10 normal controls. Benign MS patients
      also underwent conventional brain MRI and magnetization transfer imaging, which
      was compared with an identical examination obtained 1 year before. Quantitative
      structural magnetic resonance measures were baseline and changes over time in T2
      lesion volume, magnetization transfer ratio in T2 lesions and normal-appearing
      brain and total brain volume. RESULTS: Movement-related activation was greater in
      patients with benign MS than in those with relapsing-remitting MS or normal
      controls, extensively involving bilateral regions of the sensorimotor network as
      well as basal ganglia, insula and cerebellum. Greater activation correlated with
      lower T2-lesion magnetization transfer ratio, and with decreasing brain volume
      and increasing T2 lesion volume. CONCLUSIONS: The results suggest that bilateral
      brain networks, beyond those normally engaged in motor tasks, are recruited
      during a simple hand movement in patients with benign MS. This increased
      activation is probably the expression of an extensive, compensatory and tissue
      damage related functional cortical reorganization. This can explain, at least in
      part, the favourable clinical expression of patients with benign MS.

PMID- 20670980
TI  - A case of cerebral aquaporinopathy.
AB  - A 35-year-old woman was hospitalized due to impaired consciousness. Magnetic
      resonance imaging (MRI) revealed multiple parenchymal lesions in supra and
      infratentorial brain regions, which were considered responsible for her declining
      consciousness level. She was treated with intravenous methylprednisolone.
      Neurological symptoms improved and she was discharged. She was readmitted 14
      months later due to intractable hiccups. A follow-up brain MRI revealed an
      abnormal signal near the area postrema in the dorsal medulla. Serum aquaporin-4
      antibody levels were positive, but there were no visual manifestations or
      myelitis. Spinal MRI was negative for longitudinally extended transverse myelitis
      throughout the clinical course.

PMID- 20670981
TI  - Basal ganglia and frontal/parietal cortical atrophy is associated with fatigue in
      relapsing-remitting multiple sclerosis.
AB  - BACKGROUND: Fatigue is one of the most frequent symptoms suffered by patients
      affected by multiple sclerosis. The patho-physiological basis of multiple
      sclerosis-related fatigue remains to be elucidated. OBJECTIVE: Our aim was to
      investigate whether a particular pattern of deep and/or cortical grey matter
      atrophy is associated with fatigue in patients with multiple sclerosis. METHODS:
      A total of 152 patients with relapsing-remitting multiple sclerosis were
      evaluated with the Expanded Disability Status Scale, the Fatigue Severity Status
      Scale (FSS), the Modified Fatigue Impact Scale and the Beck Depression Inventory.
      The thalamic and basal ganglia volume and the regional cortical thickness were
      analysed by means of FreeSurfer. RESULTS: Based on Fatigue Severity Status Scale
      score, patients were divided into fatigued (FSS >= 4, 71 patients, 46.6%) and non
      fatigued (FSS < 4, 81 patients, 53.4%). A significant atrophy of striatum,
      thalamus, superior frontal gyrus and inferior parietal gyrus was observed in
      fatigued patients compared with non-fatigued patients. The cognitive domain of
      Modified Fatigue Impact Scale significantly correlated with the volume of the
      striatum and with the cortical thickness of the posterior parietal cortex and
      middle frontal gyrus (R = 0.51-0.61), while the physical domain of Modified
      Fatigue Impact Scale significantly correlated with striatum volume and superior
      frontal gyrus cortical thickness (R = 0.50-0.54). CONCLUSIONS: The regional
      analysis of deep and cortical grey matter atrophy suggests an association between
      the neurodegenerative process taking place in the striatum-thalamus-frontal
      cortex pathway and the development of fatigue in relapsing-remitting multiple
      sclerosis. The inclusion of the posterior parietal cortex as one of the best
      predictors of the Modified Fatigue Impact Scale cognitive domain suggests the
      major role of the posterior attentional system in determining cognitive fatigue
      in relapsing-remitting multiple sclerosis.

PMID- 20670982
TI  - Diagnosing multiple sclerosis at a later age: more than just progressive
      myelopathy.
AB  - BACKGROUND: Multiple sclerosis (MS) is usually considered a 'young persons'
      disease', typically presenting between the ages of 20 and 40. In this study we
      review our experience with patients diagnosed at age 60 or over, with particular
      emphasis on patients who continue to have evidence of active inflammation despite
      a later onset. METHODS: We reviewed all cases of MS diagnosed at or over age 60
      in our center over a 5-year period. We identified 111 patients and recorded their
      clinical and imaging characteristics using prespecified variables. Analyses were
      performed to describe their interval to diagnosis, clinical syndromes, imaging
      and laboratory characteristics. RESULTS: At the time of diagnosis, 8% of patients
      had a clinically isolated syndrome, 33% were in the relapsing-remitting stage,
      while 23% had a secondary progressive course, and 32% were primary progressive.
      Eighty-eight percent of patients had a brain MRI judged 'typical for MS', and 32%
      of all patients receiving gadolinium had enhanced lesions. Forty-six percent of
      patients with relapsing-remitting MS or clinically isolated syndrome exhibited
      gadolinium enhancement. Myelitis was the most common initial clinical syndrome,
      and progressive myelopathy was a common but not exclusive clinical syndrome at
      the time of diagnosis. CONCLUSIONS: A relapsing pattern of MS is not uncommon,
      even in patients diagnosed over the age of 60. Active inflammation (clinical
      relapses and gadolinium enhancement) occurs in a significant number of patients
      with MS with later diagnosis. These observations have implications for evaluation
      and treatment of patients with MS presenting at an older age.

PMID- 20670983
TI  - The Multiple Sclerosis Severity Score: associations with MC1R single nucleotide
      polymorphisms and host response to ultraviolet radiation.
AB  - BACKGROUND: Multiple sclerosis outcome may be influenced by ultraviolet radiation
      and vitamin D synthesis, suggesting skin type and genes determining this
      phenotype are candidates for disability. However, though associations between
      melanocortin 1 receptor (MC1R) single nucleotide polymorphisms and disability are
      reported, some data are incompatible with their expected influence on skin type.
      OBJECTIVE: Determine which MC1R single nucleotide polymorphisms affect disability
      and establish if ultraviolet radiation modifies such associations. METHODS: We
      studied using linear regression in 525 cases, associations of the Multiple
      Sclerosis Severity Score (MSSS) with skin type, gender, ultraviolet radiation
      exposure and six MC1R single nucleotide polymorphisms (rs1805005, rs1805006,
      rs2228479, rs1805007, rs1805008, rs1805009). RESULTS: CG(294) with GG(294)
      genotypes (rs1805009) (coefficient = -1.44, 95% CI -2.30, -0.59, mean MSSS +/- SD
      = 4.33 +/- 2.87) and AC(84) (rs1805006) (coefficient = 1.62, 95% CI 0.17, 3.06,
      mean MSSS = 7.62 +/- 2.43) were associated with MSSS. Associations with Asp294His
      were found in those with skin types 1/2 and 3/4, and cases stratified by
      ultraviolet radiation exposure. However, they were seen only in cases with a
      history of childhood sunburn and not in those without sunburn. We found no
      significant associations between exposure parameters and MSSS. CONCLUSIONS:
      Multiple sclerosis outcome is influenced by interactions between host response to
      ultraviolet radiation and MC1R single nucleotide polymorphisms. The influence of
      the single nucleotide polymorphisms appears distinct from their association with
      skin type.

PMID- 20670984
TI  - High risk of MS in Iranian immigrants in Gothenburg, Sweden.
AB  - BACKGROUND: In this study we investigated the risk of multiple sclerosis (MS) in
      migrants who had moved from Iran to Gothenburg, Sweden. METHODS: Patients born in
      Iran were retrieved from a population-based cohort, which included 534 MS and
      clinically isolated syndrome patients, born 1959-1990, aged 10-39 years at
      disease onset in Gothenburg. The expected versus observed number of migrants from
      Iran was calculated. RESULTS: The MS risk in the Iranian migrants in Gothenburg
      was several times higher than in Isfahan, Iran (hazard ratio 3.88, 95% confidence
      interval 2.17-6.40). Compared with the general population of Gothenburg, the
      observed number of 17 Iranian patients was higher than the expected value of 9.89
      (hazard ratio 1.72, 95% confidence interval 1.00-2.75). CONCLUSION: Migration
      from a medium-risk to a high-risk area may increase the MS risk to that of the
      high-risk area.

PMID- 20670985
TI  - Preclinical studies of methylthioadenosine for the treatment of multiple
      sclerosis.
AB  - BACKGROUND: Methylthioadenosine (MTA) is a natural metabolite with
      immunomodulatory properties. MTA improves the clinical course and pathology of
      the animal model of multiple sclerosis, even when therapy is started after
      disease onset. OBJECTIVE: Our aim was to compare the efficacy of MTA in
      ameliorating experimental autoimmune encephalomyelitis (EAE) compared with first
      line approved therapies, to develop an oral formulation of MTA and to assess its
      pharmacokinetic profile. METHODS: EAE was induced in C57BL/6 mice by immunization
      with MOG(35-55) peptide in Freund's Adjuvant. Animals were treated with MTA,
      interferon-beta or glatiramer acetate starting the day of immunization and the
      clinical score was collected blind. Pharmacokinetic studies were performed in
      Sprague Dawley rats by administering MTA by intraperitoneal injection and orally,
      and collecting blood at different intervals. MTA levels were measured by high
      performance liquid chromatography. RESULTS: We found that MTA ameliorated EAE in
      a dose-response manner. Moreover, the highest dose of MTA (60 mg/kg) was more
      efficacious than mouse interferon-beta or glatiramer acetate. We developed a salt
      of MTA for oral administration, with similar dose-response effect in the EAE
      model. Combination therapy assays between MTA and interferon-beta or glatiramer
      acetate were more effective than the individual therapies. Finally, oral MTA half
      life was 20 min, with a C(max) of 80 mg/L and without signs of obvious toxicity
      (animal death, behavioural changes, liver enzymes). CONCLUSIONS: In the EAE model
      MTA is more efficacious than first line therapies for multiple sclerosis, with a
      dose- response effect and higher efficacy when combined with interferon-beta or
      glatiramer acetate. Oral MTA was also effective in the animal model of multiple
      sclerosis.

PMID- 20670986
TI  - Modifications to the McDonald MRI dissemination in space criteria for use in
      Asians with classic multiple sclerosis: the Taiwanese experience.
AB  - BACKGROUND: The McDonald MRI dissemination in space criteria have been found to
      be less sensitive when applied to Asians with classic multiple sclerosis. The
      Asian neurological community thus proposed modifications to the criteria with
      reduction of minimal number of T2 lesions from nine to four, and removal of
      restriction on spinal cord lesion length and morphology for use in Asians.
      OBJECTIVE: The study is to examine the accuracy of modified MRI dissemination in
      space criteria for prediction of conversion from clinically isolated syndrome to
      definite multiple sclerosis according to patients' baseline MRI. METHODS: From
      2001 to 2007, we recruited 67 patients with clinically isolated syndrome. They
      had been followed-up until development of definite multiple sclerosis or
      remaining as clinically isolated syndrome for more than 2 years. The non
      converters were taken as negative cases. The 67 patients' baseline MRIs were
      evaluated by two radiologists and determined as either fulfilling or not
      fulfilling McDonald and modified MRI criteria for dissemination in space.
      RESULTS: Thirty-two patients converted to definite multiple sclerosis and 35 did
      not. The modified criteria are slightly more sensitive (53.1% vs. 50.0%) and
      accurate (77.6% vs. 76.1%) as compared with McDonald criteria. However, further
      reduction of the cutoff of abnormal MRI criteria from three of four to two of
      four criteria yields best sensitivity (71.9%) and accuracy (83.6%). CONCLUSIONS:
      Modifications to the McDonald MRI dissemination in space criteria (by using fewer
      T2 lesions, removal of the restriction on the spinal cord lesion and reduction of
      the cutoff of MRI criteria) are more appropriate for use in the Taiwanese
      population for the diagnosis of classic multiple sclerosis.

PMID- 20670987
TI  - In vivo anti-inflammatory effect and toxicological screening of Maytenus
      heterophylla and Maytenus senegalensis extracts.
AB  - Maytenus heterophylla (Eckl & Zeyh.) Robson and Maytenus senegalensis (Lam).
      Exell are two African medicinal plants used to treat painful and inflammatory
      diseases. We evaluated the in vivo (per os) anti-inflammatory activity of M.
      heterophylla leaf, stem and root extracts and of M. senegalensis leaf and stem
      extracts. Additionally, we assessed their in vivo acute and sub-acute toxicities.
      Anti-inflammatory activities of ethanol extracts were determined in Wistar albino
      rats, by the carrageenan-induced paw oedema method. Acute and sub-acute toxicity
      screening of the extracts was evaluated in adult male CD-6 mice. Leaf extracts of
      M. heterophylla and M. senegalensis exhibited significant anti-inflammatory
      activity (120 mg/kg, per os), reducing oedema by 51% and 35%, respectively. While
      M. heterophylla extracts at 1200 mg/kg have shown to be non-toxic, M.
      senegalensis extracts indicated some toxicity. Our results show a significant
      anti-inflammatory effect of both M. heterophylla and M. senegalensis leaf
      extracts in a local model of acute inflammation and suggest the absence of acute
      and sub-acute toxicity signs of the M. heterophylla leaf extract (but not of M.
      senegalensis). Ongoing studies will surely shed some light into the mechanism of
      action of this active extract and establish its chemical fingerprint.

PMID- 20670988
TI  - A double-suicide autopsy case of  potassium poisoning by intravenous 
      administration of potassium aspartate  after intake of some 
      psychopharmaceuticals.
AB  - We report a curious double-suicide autopsy case of both male and female who died
      of potassium poisoning by intravenous administration of concentrated potassium
      aspartate solution. The plasma concentrations of potassium of the male and female
      subjects were as high as 49.7 and 62.8 mEq/L, respectively. In addition to the
      high concentrations of potassium, toxic levels of phenobarbital, promethazine and
      chlorpromazine, and relatively low levels of etizolam and brotizolam were also
      detected from whole blood and urine specimens of both cadavers. Twenty empty
      plastic bottles (10-mL capacity) labeled 'ASPARA(r) Potassium Injection 10 mEq'
      were found at the suicide spot. To our knowledge, this is the first description
      for suicidal death by potassium aspartate; in all of the previous literature,
      they used potassium chloride intravenously or per os.

PMID- 20670989
TI  - Cell-cycle blockage associated with increased apoptotic cells in the thymus of
      chickens fed on diets high in fluorine.
AB  - Three hundred 1-day-old Avian broilers were divided into four groups and fed on
      control diet (fluorine 23 mg/kg) and high-fluorine (F) diets (400 mg/kg, high-F
      group I; 800 mg/kg, high-F group II; 1200 mg/kg, high-F group III) for 42 days (n
      = 75/group). The growth index (GI) was obviously decreased in the three high-F
      groups, which indicated the inhibited development of thymus. Histopathologically,
      the population of thymocytes was decreased in the thymic lobule in the three high
      F groups. As measured by flow cytometry, thymocytes in G(0)/G(1) phase were
      significantly increased while thymocytes in S phase, G(2) + M phase and
      proliferating index (PI) value were obviously decreased in the three high-F
      groups. Also, the percentage of apoptotic thymocytes was greatly increased in the
      three high-F groups when compared with that of control group. At the same time,
      the occurrence frequencies of apoptotic thymocyte were markedly increased in the
      three high-F groups, with the appearance of dilated endoplasmic reticulum in high
      F groups II and III ultra-structurally. The results showed that excess dietary F
      in the range of 400-1200 mg/kg caused histological lesions, G(0)/G(1) arrest and
      cellular apoptosis in the thymus, which inhibited the development of thymus and
      finally led to impaired cellular immune function.

PMID- 20670990
TI  - An unusual case of mesalazine intoxication: oral and rectal overloading of the
      rectal suppository form.
AB  - Drugs containing 5-acetylsalicylic acid (5-ASA) have been commonly used for
      inflammatory bowel diseases for more than half a century, but no case about
      overdose of suppository form of mesalazine which was taken both orally and
      rectally has been reported in the related literature up to now. In the present
      case, a 20-year-old male patient who took 14.5 g of mesalazine rectally and
      orally for suicide purpose is discussed. He was an ulcerative colitis patient and
      depressed about his illness and routine life traffic. Although it was hard for
      him to take the suppository form orally because of its bad taste and structure,
      he took it with the help of water. In the patient's colonoscopy, diffuse
      hyperemia and edema extending from the anal channel to the proximal rectal mucosa
      and a 1.5 cm diameter ulcer expanding from anal channel through the rectum were
      identified. No pathology was found in the upper gastrointestinal endoscopy.
      Routine laboratory examination was performed and no abnormality was identified in
      the patient's total blood account, biochemical parameters and full-urine
      examination. In the control rectoscopy applied to the patient 15 days later,
      recovery of the ulcer was observed and he was discharged to be followed in the
      psychiatry clinic.

PMID- 20670991
TI  - Just who is at risk? The ethics of environmental regulation.
AB  - The willingness to view risk as part of daily life has vanished. A risk-averse
      mindset among environmental regulators engenders confusion between the ethics of
      intention and the ethics of consequence, leading to the elevation of the
      precautionary principle with unintended and often unfortunate outcomes.
      Environmental risk assessment is conservative, but the actual level of
      conservatism cannot be determined. High-end exposure assumptions and current
      toxicity criteria from the USEPA, based on linear extrapolation for carcinogens
      and default uncertainty factors for systemic toxicants, obscure the degree of
      conservatism in risk assessments. Ideally, one could choose a percentile of the
      target population to include within environmental standards, but this choice is
      complicated by the food, pharmaceutical and advertising industries, whose
      activities, inadvertent or not, often promote maladaptive and unhealthy lifestyle
      choices. There has lately been much discussion about background exposures and
      disease processes and their potential to increase the risk from environmental
      chemicals. Should these background exposures or disease processes, especially
      those associated with maladaptive individual choices, be included as part of a
      regulatory risk evaluation? A significant ethical question is whether
      environmental regulation should protect those pursuing a self-destructive
      lifestyle that may add to or synergize with otherwise innocuous environmental
      exposures. Choosing a target percentile of protection would provide an increased
      level of transparency and the flexibility to choose a higher or lower percentile
      if such a choice is warranted. Transparency and flexibility will lead to more
      responsive environmental regulation that balances protection of public health and
      the stewardship of societal resources.

PMID- 20670992
TI  - Thrombocytopenia associated with galsulfase treatment.
AB  - Mucopolysaccharidosis type VI (MPS VI), or Maroteaux-Lamy syndrome, is a
      lysosomal storage disorder that results from a deficiency of the enzyme N
      acetylgalactosamine-4-sulfatase or arylsulfatase B (ASB). It is a relatively rare
      disorder, with an estimated incidence of 1 in 248,000 to 1 in 300,000. The
      diagnosis is made on the basis of findings of elevated urine glycosaminoglycans
      and a deficiency of ASB activity in leukocytes or cultured fibroblasts. In
      treatment of MPS VI, enzyme replacement therapy (galsulfase; human recombinant
      ASB enzyme) became available. Infusions of galsulfase were generally well
      tolerated. But in some patients, infusion-associated reactions including rash,
      urticaria, headache, hypotension, nausea, and vomiting were documented and were
      managed successfully by interrupting or slowing the rate of infusion and/or by
      the administration of antihistamines, antipyretics, corticosteroids, or oxygen.
      Here, we report a case with MPS VI who developed thrombocytopenia after third
      dose of therapy. To the best of our knowledge, this is the first report about
      thrombocytopenia associated with galsulfase therapy in the literature.
      Additionally, with this report, we want to share our approach for this case.

PMID- 20670993
TI  - Effects of uranium depletion on  1alpha-hydroxylase in kidney of rats.
AB  - This study was designed to evaluate the effects of depleted uranium (DU) on
      1alpha-hydroxylase in the kidney of rats and to delinerate the mechanism of
      damage to kidneys and bones by DU. Male Sprague-Dawley rats were surgically
      implanted with DU fragments at three dose levels (0.1 g, 0.2 g and 0.3 g). After
      3, 6 or 12 months, the concentration of 1alpha,25(OH)(2)D(3) in the kidney was
      measured by radioimmunoassay. The activity of 1alpha-hydroxylase was shown by the
      production of 1alpha,25(OH)(2)D(3) after incubation. The results showed that the
      1alpha-hydroxylase activity in the kidney was decreased after 3 months (27.2% at
      the medium dose DU group, p < 0.05; 33.4% at the high dose DU group, p < 0.01).
      In contrast, at 6 months and 12 months after implantation of DU, the activity of
      renal 1alpha-hydroxylase in DU-treated animals was not decreased significantly in
      comparison with the controls (p > 0.05). On the other hand, the activity of renal
      1alpha-hydroxylase was decreased by 33.1% (p < 0.05) and 34.4% (p < 0.01) in
      blank control groups at 6 and 12 months, respectively, when compared with the
      blank control group at 3 months. In conclusion, this study showed that chronic DU
      exposure could induce renal damages and inhibit the synthesis of biologically
      active form of vitamin D, which may be the underlying mechanism of bone metabolic
      disorder caused by renal injury after DU exposure.

PMID- 20670994
TI  - Guidance for the management of headache in sport on behalf of The Royal College
      of General Practitioners and The British Association for the Study of Headache.
AB  - Headache is prevalent within the community and can have an impact on sport in
      both the amateur and elite player, either coincidentally or as a direct result of
      participation. Against a background of a limited evidence base, this paper
      suggests how headache can be classified within this context and offers guidance
      for treating both the amateur and elite athlete. The impact of headache in sport
      may be unrecognised and undertreated, and further research is needed in this
      area.

PMID- 20670995
TI  - Cluster headache associated with a sixth nerve palsy: a case report.
AB  - BACKGROUND: Cluster headache is a rare primary headache disorder characterized by
      recurrent, stereotyped short-lasting attacks of severe, unilateral head pain
      accompanied by autonomic symptoms. METHODS/RESULTS: Ophthalmic features such as
      conjunctival injection, lacrimation, ptosis and miosis occur in the vast majority
      of patients with cluster headache, whereas co-existent ocular movement disorders
      are rare. CONCLUSIONS: To the best of our knowledge, only two documented cases of
      cluster headache with external ocular movement disorders have been reported. We
      describe herein an additional case with this unusual finding and discuss the
      putative pathophysiology of cluster headache associated with ophthalmoparesis.

PMID- 20670996
TI  - Migraine diagnosis and management in general emergency departments in France.
AB  - BACKGROUND: We conducted a prospective study of patients admitted to 22 general
      emergency departments in France over 1 week. PATIENTS AND METHODS: Of 15,835
      adult patients, 483 (3.1%) had headache and 98 (0.6%) had migraine. RESULTS:
      Compared with the migraine population in France, our migraine patients were
      similar in terms of proportion of female patients (75%) and mean age (37.6 +/-
      13.8 years) but presented earlier in their disease course. Patients sought
      emergency treatment because of a severe attack (49%) or because of ineffective
      treatment (20%). Non-opioid analgesics excluding non-steroidal anti-inflammatory
      drugs (NSAIDs), and NSAIDs, were most commonly prescribed as acute treatment, yet
      it took more than 48 h for symptom resolution in 36% of 92 follow-up patients.
      CONCLUSIONS: Results suggest there is room for improvement in choice of agents
      prescribed. We propose additional education and training of clinicians to improve
      adherence to clinical practice guidelines.

PMID- 20670997
TI  - Scaling up a school-based sexual and reproductive health intervention in rural
      Tanzania: a process evaluation describing the implementation realities for the
      teachers.
AB  - Little is known about the nature and mechanisms of factors that facilitate or
      inhibit the scale-up and subsequent implementation of school-based adolescent
      sexual and reproductive health (ASRH) interventions. We present process
      evaluation findings examining the factors that affected the 10-fold scale-up of
      such an intervention, focussing on teachers' attitudes and experiences.
      Qualitative interviews and focus group discussions with teachers, head teachers,
      ward education coordinators and school committees from eight schools took place
      before, during and after intervention implementation. The results were
      triangulated with observations of training sessions and training questionnaires.
      The training was well implemented and led to some key improvements in teachers'
      ASRH knowledge, attitudes and perceived self-efficacy, with substantial
      improvements in knowledge about reproductive biology and attitudes towards
      confidentiality. The trained teachers were more likely to consider ASRH a
      priority in schools and less likely to link teaching ASRH to the early initiation
      of sex than non-trained teachers. Facilitating factors included teacher
      enjoyment, their recognition of training benefits, the participatory teaching
      techniques, support from local government as well as the structured nature of the
      intervention. Challenges included differential participation by male and female
      teachers, limited availability of materials and high turnover of trained
      teachers.

PMID- 20670998
TI  - Exploiting phytochemicals for developing a 'push-pull' crop protection strategy
      for cereal farmers in Africa.
AB  - Lepidopteran stemborers and parasitic weeds in the genus Striga are major
      constraints to efficient production of cereals, the most important staple food
      crops in Africa. Smallholder farmers are resource constrained and unable to
      afford expensive chemicals for crop protection. Development of a push-pull
      approach for integrated pest and weed management is reviewed here. Appropriate
      plants were discovered that naturally emit signalling chemicals (semiochemicals).
      Plants highly attractive for egg laying by stemborer pests were selected and
      employed as trap crops (pull), to draw pests away from the main crop. Of these,
      Napier grass, Pennisetum purpureum (Schumach), despite its attractiveness,
      supported minimal survival of the pests' immature stages. Plants that repelled
      stemborer pests, notably molasses grass, Melinis minutiflora P. Beauv., and
      forage legumes in the genus Desmodium, were selected as intercrops (push).
      Desmodium intercrops suppress Striga hermonthica (Del.) Benth. through an
      allelopathic mechanism. Their root exudates contain novel flavonoid compounds,
      which stimulate suicidal germination of S. hermonthica seeds and dramatically
      inhibit its attachment to host roots. The companion crops provide valuable forage
      for farm animals while the leguminous intercrops also improve soil fertility and
      moisture retention. The system is appropriate as it is based on locally available
      plants, not expensive external inputs, and fits well with traditional mixed
      cropping systems in Africa. To date it has been adopted by more than 30,000
      smallholder farmers in East Africa where maize yields have increased from ~1 t
      ha(-1) to 3.5 t ha(-1). Future directions for semiochemical delivery by plants
      including biotechnological opportunities are discussed.

PMID- 20671000
TI  - Paired interviews of shared experiences around chronic low back pain: classic
      mismatch between patients and their doctors.
AB  - BACKGROUND: current treatments for chronic low back pain (LBP) appear to be
      inadequate and there are growing calls for new approaches. This study explores
      the paired interviews of shared experiences among chronic LBP patients and their
      physicians with the ultimate goal of improving doctor-patient communication and
      clinical outcomes. METHODS: in-depth interviews of a purposeful sample of paired
      chronic LBP patients and their doctors were conducted, transcribed and analysed
      using a multistep iterative process. Interview pairs were examined for important
      themes and major areas of convergence and divergence/mismatch. RESULTS: patients'
      stories focused on their suffering from severe and disabling LBP while conveying
      a high level of reliance on their family physicians. Physicians described many
      challenges in treating this patient population. Patient and doctor stories were
      convergent regarding the severity/seriousness of illness, the lack of effective
      treatments and the existence of many barriers to care. Notable areas of mismatch:
      biomedical/biomechanical versus biopsychosocial (BPS) models of illness,
      treatment expectations/goals of reducing pain versus improving function and the
      importance of a definitive diagnosis. DISCUSSION: patient and physician stories
      revealed shared themes and convergences, as well as significant discordance and
      mismatch. Family physicians, trained in and adherent to the BPS model, may have
      great difficulty when matched with biomechanically oriented patients. Re
      conceptualizing doctors and LBP patients as a single teachable dyad may be
      useful. Clinical application of paired interviews of shared experiences may be
      useful in bridging communication and paradigmatic gaps, reducing mismatch and
      developing shared treatment plans.

PMID- 20671001
TI  - The need to improve the interface between in-hours and out-of-hours GP care, and
      between out-of-hours care and self-care.
AB  - BACKGROUND: considerable changes have occurred over the last 5 years in the
      organization of out-of-hours care in the UK. Users' experiences of their care are
      an important part of 'quality of care' and are valuable for identifying areas for
      improvement. AIM: to identify strengths and weaknesses of out-of hours service
      provision in Wales. The design of the study is a cross-sectional survey. The
      setting of the study is nine GP services, three Accident and Emergency units and
      NHS Direct in Wales. METHOD: survey using the validated Out-of-Hours
      questionnaire. We identified the four most and least favourably rated items
      regarding users' experience of care. These were analysed by type of care
      provided, telephone advice, treatment centre and home visit groups. RESULTS:
      eight hundred and fifty-five of 3250 users responded (26% response rate). Across
      providers and types of care, consistent strengths were the 'manner of treatment
      by call operator' and the 'explanation of the next step by call operator'.
      Consistent weaknesses were the 'speed of call back by the clinician', the
      'information provided by the GP', 'getting medication after the consultation' and
      'when to contact the (in-hours) GP'. CONCLUSIONS: users of out-of-hours care
      identify clear and consistent strengths and weaknesses of service provision
      across Wales. Specific areas for improvement concern the interface between in
      hours care and out-of-hours care and between out-of-hours care and self-care. GP
      surgeries need to give better information on how to access the out-of-hours
      services. Out-of-hours providers should improve their advice on how and when to
      access in-hours surgeries and also improve the availability of medicines after
      out-of-hours consultations.

PMID- 20671002
TI  - Delays in response and triage times reduce patient satisfaction and enablement
      after using out-of-hours services.
AB  - BACKGROUND: several different models of out-of-hours primary care now exist in
      the UK. Important outcomes of care include users' satisfaction and enablement to
      manage their illness or condition, but the determinants of these outcomes in the
      unscheduled care domain are poorly understood. Aim. To identify predictors of
      user satisfaction and enablement across unscheduled care or GP out-of-hours
      service providers in Wales. The design of the study is a cross-sectional survey.
      The setting of the study is nine GP out-of-hours services, three Accident and
      Emergency units and an all Wales telephone advice service in Wales. METHODS:
      postal survey using the Out-of-hours Patient Questionnaire. Logistic regression
      was used to fit both satisfaction and enablement models, based on demographic
      variables, service provider and treatment received and perceptions or ratings of
      the care process. RESULTS: eight hundred and fifty-five of 3250 users responded
      (26% response rate, range across providers 14-41%, no evidence of non-response
      bias for age or gender). Treatment centre consultations were significantly
      associated with decreased patient satisfaction and decreased enablement compared
      with telephone advice. Delays in call answering or callback for triage and
      shorter consultations were significantly associated with lower satisfaction.
      Waiting more than a minute for initial call answering was associated with lower
      enablement. CONCLUSIONS: giving users more time to discuss their illness in
      consultations may enhance satisfaction and enablement but this may be resource
      intensive. More simple interventions to improve access by quicker response and
      triage, and keeping users informed of waiting times, could also serve to increase
      satisfaction and ultimately impact on their enablement.

PMID- 20671003
TI  - Synthesis, characterization and sintering behaviour of indialite ceramic from fly
      ash.
AB  - Indialite ceramic was prepared using fly ash and magnesium carbonate powder as
      precursors. The effects of sintering aids LiOH . H2O and TiO2 on its
      crystallization and morphology evolution were studied as well. X-ray diffraction
      results indicated that the formation of indialite was achieved by solid-state
      sintering reactions at 1200  degrees C for 4 h. With increasing amounts of LiOH .
      H2O, the viscosity decreased and beta-spodumene, spinel phases started to develop
      at the expense of indialite. Scanning electron microscopy observations revealed
      that the surface of the sintered samples became smoother with higher porosity
      losses and grain size reduction. As the TiO2 contents increased from 4 to 10%,
      dauphine-twinned quartz and rutile were formed by simultaneously consuming
      indialite. In this process, the viscosity showed no significant changes.

PMID- 20671004
TI  - In-field experimental verification of cultivation of microalgae Chlorella sp.
      using the flue gas from a cogeneration unit as a source of carbon dioxide.
AB  - A complex treatment of agricultural waste including the following major steps:
      anaerobic fermentation of suitable waste, cogeneration of the obtained biogas and
      growth of microalgae consuming the CO(2) from biogas and flue gas was verified
      under field conditions in a pilot-scale photobioreactor. The growth kinetics of
      microalgae Chlorella sp. consuming mixture of air and carbon dioxide (2% (v/v) of
      CO(2)), or flue gas (8-10% (v/v) of CO(2)) was investigated. The results obtained
      in the pilot photobioreactor were compared with results previously measured in
      laboratory photobioreactors. The field tests were performed in a pilot-scale
      outdoor solar-bubbled photobioreactor located at a biogas station. The pilot
      scale photobioreactor was in the shape of a flat and narrow vertical prism with a
      volume of 300 L. The microalgae growth rates were correlated with empirical
      formulas. Laboratory analyses of the produced microalgae confirmed that it meets
      the strict EU criteria for relevant contaminants level in foodstuffs. Utilization
      of flue gases from cogeneration therefore was not found to be detrimental to the
      quality of microalgal biomass, and may be used in these types of bioreactors.

PMID- 20671005
TI  - A formal feasibility study of sublingual methadone for breakthrough cancer pain.
AB  - We conducted a feasibility study of sublingual methadone for breakthrough cancer
      pain, to determine whether a larger, randomized trial was warranted, and to
      identify a study design that would be likely to succeed. From approximately 1930
      patients in the initial pool, nine patients were enrolled. Five patients
      completed the study, generating data on 83 discrete episodes of breakthrough
      cancer pain at optimal dose. Mean pain intensity dropped by 1.7 points (on a 10
      point numerical scale) within 10 min of sublingual methadone administration, and
      by 3.2 points after 15 min. No serious or severe toxicity was encountered. Based
      on the results of this feasibility study, a larger randomized clinical trial of
      sublingual methadone for breakthrough cancer pain using this trial model would
      not be successful. Extensive information obtained from small numbers of carefully
      studied patients provides proof of concept that sublingual methadone is
      effective, safe, and well tolerated.

PMID- 20671006
TI  - Effectiveness of antiepileptic or antidepressant drugs when added to opioids for
      cancer pain: systematic review.
AB  - Neuropathic pain mechanisms are present in up to 40% of patients with cancer
      pain. In these situations, additional or adjuvant analgesic drugs (such as
      antidepressants or antiepileptics) are often required to optimize pain control
      alongside standard opioid therapy. This systematic review aimed to determine the
      effectiveness of antidepressants and antiepileptics when added to opioids,
      compared to opioids alone, for the management of pain caused directly by cancer.
      Prospective clinical studies, published in English that used a before-after
      design or randomized or non-randomized group comparisons were identified. Data
      were extracted on pain intensity, pain relief and adverse events. Eight studies
      were eligible (five randomized controlled trials) that recruited 465 patients in
      total, of whom 370 (79.5%) completed the study period. A narrative analysis was
      performed because clinical and methodological heterogeneity prevented meta
      analysis. Included studies suggested that adjuvants improve pain control within 4
      8 days when added to opioids for cancer pain; the strongest evidence supports
      gabapentin. However, a reduction in pain intensity of greater than 1 point on a 0
      10 numerical rating scale is unlikely, but an increase in adverse events is
      likely. For all adjuvants, the effect size was much less than that seen in
      patients with non-cancer neuropathic pain. Dosing strategies that can be examined
      in future clinical trials are suggested.

PMID- 20671007
TI  - The use of morphine to control pain in advanced cancer: an investigation of
      clinical usage in Bangladesh.
AB  - In 2007, 13% of all deaths worldwide were due to cancer, and of these 72%
      occurred in low- and middle-income countries. Opioids are essential for the
      successful delivery of palliative care and pain control. This paper reports data
      from a cross-sectional survey that aimed to investigate the use of morphine in
      advanced cancer in palliative care setting in Bangladesh, in order to inform
      clinical practice and fledgling service development. The study was a single semi
      structured qualitative interview study. Cancer patients, family members and
      palliative care specialists (20 in total) were interviewed in two medical
      settings. Transcripts were transcribed verbatim, translated and cross-checked
      with two local interpreters. Data were imported into NVIVO 8 for coding. A coding
      frame was generated following line by line coding. Relational codes were
      established following peer review of coding units and the resulting frame.
      Despite having been under the pain and palliative care clinics only six out of 10
      patients had received morphine. Lack of morphine availability resulted in
      physical suffering of patients and emotional distress of their families. Lack of
      availability of morphine was identified as the main barrier to pain control.
      International attention and collaboration with local policy makers is needed to
      simplify narcotic regulations and increase the availability of morphine.

PMID- 20671012
TI  - UK aid policy focuses on family planning for world's women.

PMID- 20671014
TI  - Calcium supplements in people with osteoporosis.

PMID- 20671013
TI  - Effect of calcium supplements on risk of myocardial infarction and cardiovascular
      events: meta-analysis.
AB  - OBJECTIVE: To investigate whether calcium supplements increase the risk of
      cardiovascular events. DESIGN: Patient level and trial level meta-analyses. DATA
      SOURCES: Medline, Embase, and Cochrane Central Register of Controlled Trials
      (1966-March 2010), reference lists of meta-analyses of calcium supplements, and
      two clinical trial registries. Initial searches were carried out in November
      2007, with electronic database searches repeated in March 2010. STUDY SELECTION:
      Eligible studies were randomised, placebo controlled trials of calcium
      supplements (>or=500 mg/day), with 100 or more participants of mean age more than
      40 years and study duration more than one year. The lead authors of eligible
      trials supplied data. Cardiovascular outcomes were obtained from self reports,
      hospital admissions, and death certificates. RESULTS: 15 trials were eligible for
      inclusion, five with patient level data (8151 participants, median follow-up 3.6
      years, interquartile range 2.7-4.3 years) and 11 with trial level data (11 921
      participants, mean duration 4.0 years). In the five studies contributing patient
      level data, 143 people allocated to calcium had a myocardial infarction compared
      with 111 allocated to placebo (hazard ratio 1.31, 95% confidence interval 1.02 to
      1.67, P=0.035). Non-significant increases occurred in the incidence of stroke
      (1.20, 0.96 to 1.50, P=0.11), the composite end point of myocardial infarction,
      stroke, or sudden death (1.18, 1.00 to 1.39, P=0.057), and death (1.09, 0.96 to
      1.23, P=0.18). The meta-analysis of trial level data showed similar results: 296
      people had a myocardial infarction (166 allocated to calcium, 130 to placebo),
      with an increased incidence of myocardial infarction in those allocated to
      calcium (pooled relative risk 1.27, 95% confidence interval 1.01 to 1.59,
      P=0.038). CONCLUSIONS: Calcium supplements (without coadministered vitamin D) are
      associated with an increased risk of myocardial infarction. As calcium
      supplements are widely used these modest increases in risk of cardiovascular
      disease might translate into a large burden of disease in the population. A
      reassessment of the role of calcium supplements in the management of osteoporosis
      is warranted.

PMID- 20671015
TI  - Dabigatran etexilate in people with atrial fibrillation.

PMID- 20671016
TI  - Assessing expressed emotion in mothers of children with autism: the Autism
      Specific Five Minute Speech Sample.
AB  - BACKGROUND: Expressed emotion (EE) is a measure of family emotional climate found
      to be predictive of symptom levels in a range of psychiatric, medical, and
      developmental disorders, including autism. METHOD: Employing data from 104
      mothers of children with autism, this study examines the Autism-Specific Five
      Minute Speech Sample (AFMSS), a modified EE coding system based on the widely
      used Five Minute Speech Sample (Magana et al., 1986). FINDINGS: With the
      exception of one EE component, emotional over-involvement, the revised coding
      system demonstrated adequate internal consistency and good to excellent inter
      rater and code-recode reliability. It also demonstrated acceptable validity,
      based on its significant correlations with factors linked to EE in previous
      research. Regression analyses also indicated AFMSS-EE to be a significant
      predictor of child social competence, but not child problem behaviors.
      DISCUSSION: While further testing is required, the AFMSS appears to be a useful
      method of assessing EE within the context of parenting children with autism and
      related disorders.

PMID- 20671017
TI  - Memory and the self in autism: A review and theoretical framework.
AB  - This article reviews research on (a) autobiographical episodic and semantic
      memory, (b) the self-reference effect, (c) memory for the actions of self versus
      other (the self-enactment effect), and (d) non-autobiographical episodic memory
      in autism spectrum disorder (ASD), and provides a theoretical framework to
      account for the bidirectional relationship between memory and the self in ASD. It
      is argued that individuals with ASD have diminished psychological self-knowledge
      (as a consequence of diagnostic social and communication impairments), alongside
      intact physical self-knowledge, resulting in an under-elaborated self-concept.
      Consequently, individuals with ASD show impaired autobiographical episodic memory
      and a reduced self-reference effect (which may each rely on psychological aspects
      of the self-concept) but do not show specific impairments in memory for their own
      rather than others' actions (which may rely on physical aspects of the self
      concept). However, it is also argued that memory impairments in ASD (e.g., in non
      autobiographical episodic memory) may not be entirely accounted for in terms of
      self-related processes. Other factors, such as deficits in memory binding, may
      also play a role. Finally, it is argued that deficits in autobiographical
      episodic memory and future thinking may result in a diminished temporally
      extended self-concept in ASD.

PMID- 20671018
TI  - The Streptococcus mutans Cid and Lrg systems modulate virulence traits in
      response to multiple environmental signals.
AB  - The tight control of autolysis by Streptococcus mutans is critical for proper
      virulence gene expression and biofilm formation. A pair of dicistronic operons,
      SMU.575/574 (lrgAB) and SMU.1701/1700 (designated cidAB), encode putative
      membrane proteins that share structural features with the bacteriophage-encoded
      holin family of proteins, which modulate host cell lysis during lytic infection.
      Analysis of S. mutans lrg and cid mutants revealed a role for these operons in
      autolysis, biofilm formation, glucosyltransferase expression and oxidative stress
      tolerance. Expression of lrgAB was repressed during early exponential phase and
      was induced over 1000-fold as cells entered late exponential phase, whereas cidAB
      expression declined from early to late exponential phase. A two-component system
      encoded immediately upstream of lrgAB (LytST) was required for activation of
      lrgAB expression, but not for cid expression. In addition to availability of
      oxygen, glucose levels were revealed to affect lrg and cid transcription
      differentially and significantly, probably through CcpA (carbon catabolite
      protein A). Collectively, these findings demonstrate that the Cid/Lrg system can
      affect several virulence traits of S. mutans, and its expression is controlled by
      two major environmental signals, oxygen and glucose. Moreover, cid/lrg expression
      is tightly regulated by LytST and CcpA.

PMID- 20671019
TI  - A locus necessary for the transport and catabolism of erythritol in Sinorhizobium
      meliloti.
AB  - In this work we have genetically defined an erythritol utilization locus in
      Sinorhizobium meliloti. A cosmid containing the locus was isolated by
      complementation of a transposon mutant and was subsequently mutagenized using Tn5
      : : B20. The locus was found to consist of five transcriptional units, each of
      which was necessary for the utilization of erythritol. Genetic complementation
      experiments using genes putatively annotated as erythritol catabolic genes
      clearly showed that, of the 17 genes at this locus, six genes are not necessary
      for the utilization of erythritol as a sole carbon source. The remaining genes
      encode EryA, EryB, EryC and TpiB as well as an uncharacterized ABC-type
      transporter. Transport experiments using labelled erythritol showed that
      components of the ABC transporter are necessary for the uptake of erythritol. The
      locus also contains two regulators: EryD, a SorC class regulator, and SMc01615, a
      DeoR class regulator. Quantitative RT-PCR experiments showed that each of these
      regulators negatively regulates its own transcription. In addition, induction of
      the erythritol locus was dependent upon EryD and a product of erythritol
      catabolism. Further characterization of polar mutations revealed that in addition
      to erythritol, the locus contains determinants for adonitol and l-arabitol
      utilization. The context of the mutations suggests that the locus is important
      for both the transport and catabolism of adonitol and l-arabitol.

PMID- 20671020
TI  - When budgets are tight, there are better options than colonoscopies for
      colorectal cancer screening.
AB  - A critical challenge facing cancer screening programs, particularly those aimed
      at uninsured people with low incomes, is choosing the screening test that makes
      the most efficient use of limited budgets. For colorectal cancer screening, there
      is growing momentum to use colonoscopy, which is an expensive test. In this
      study, we modeled scenarios to assess whether the use of fecal occult blood tests
      or colonoscopy provides the most benefit under conditions of budget constraints.
      We found that although colonoscopy is more accurate, under most scenarios, fecal
      occult blood tests would result in more individuals' getting screened, with more
      life-years gained.

PMID- 20671021
TI  - Changes in disease characteristics and response rates among patients in the
      United Kingdom starting anti-tumour necrosis factor therapy for rheumatoid
      arthritis between 2001 and 2008.
AB  - OBJECTIVES: Anti-TNF therapy has significantly improved outcomes for patients
      with severe RA. In the UK, changing financial restrictions and increasing
      experience with their use may have resulted in changes to the way physicians use
      anti-TNF therapies. The aim of this analysis was to examine changes in disease
      characteristics and response rates among patients starting anti-TNF therapy for
      RA over an 8-year period. METHODS: A total of 11 216 RA patients registered
      between 2001 and 2008 with the British Society for Rheumatology Biologics
      Register were included and stratified according to year of first anti-TNF
      prescription. Baseline characteristics and treatment response were compared year
      on year using logistic and linear regression models. RESULTS: Mean RA disease
      activity and severity of new anti-TNF-treated patients decreased between 2001 and
      2008. The mean disease duration remained high (11 years in 2008) although the
      proportion of patients having disease duration<5 years increased significantly
      (2001: 9%; 2008: 29%; P<0.001). The majority of patients had failed three DMARDs
      on average before the first anti-TNF prescription. There was an increase in both
      the proportion of EULAR good responders at 1 year (2001: 18%; 2008: 30%; P<0.001)
      and in the number of patients achieving remission (2001: 8%; 2008: 17%; P<0.001).
      Drug survival remained relatively stable over the study years. CONCLUSIONS: There
      is a significant trend towards earlier use of anti-TNF therapies in patients with
      less severe disease, although the mean disease duration at first treatment
      remains high. This has correlated with improvements in outcome. These results
      support the earlier use of anti-TNF therapies in RA.

PMID- 20671022
TI  - Meta-analysis of tight control strategies in rheumatoid arthritis: protocolized
      treatment has additional value with respect to the clinical outcome.
AB  - OBJECTIVES: Tight control studies including regular assessments of disease
      activity have shown that this approach has beneficial effects on disease
      activity, disability and joint damage in treating RA patients. Some of these
      studies included tight control with protocolized treatment, while others applied
      tight control without protocolized treatment. The aim of this study was to
      compare the effects of tight control with usual care and to compare the effects
      of tight control studies with and without protocolized treatment adjustments.
      METHODS: A systematic literature search was performed to identify clinical trials
      in RA that evaluated tight control strategies in comparison with usual care. Two
      types of study were compared: (i) those using disease activity monitoring with
      protocolized treatment adjustments, and (ii) those using disease activity
      monitoring without protocolized treatment adjustments. The databases PubMed and
      Cochrane were searched from 1995 up to 2009. Primary outcome measure was the mean
      change in the 28-joint DAS (DAS-28), which was used in a random-effects meta
      analysis. RESULTS: Six controlled trials regarding tight control in RA patients
      were included in the meta-analysis. In all trials, patients treated in the tight
      control arms had significantly higher DAS-28 responses than patients treated
      according to usual care [weighted mean difference (WMD) = 0.59, P < 0.001].
      Moreover, tight control was significantly more effective (P < 0.001) by means of
      protocolized treatment adjustments (WMD = 0.97) compared with non-protocolized
      monitoring of disease activity (WMD = 0.25). CONCLUSION: Tight control in RA
      resulted in significantly better clinical outcomes than usual care. It is
      suggested but not proved that tight control with protocolized treatment
      adjustments is more beneficial than if no such protocol is used.

PMID- 20671023
TI  - Proton pump inhibitors interfere with the immunosuppressive potency of
      mycophenolate mofetil.
AB  - OBJECTIVES: MMF is cleaved in the acidic milieu of the gastric compartment.
      However, its absorption might be impeded by proton pump inhibitors (PPIs), which
      suppress acid production and thus increase stomach pH. Since PPIs are widely
      used, it is useful to clarify whether the total drug amount of MMF is available
      in patients undergoing PPI treatment. METHODS: We analysed 36 patients with
      autoimmune diseases under stable MMF maintenance therapy. Twenty-three patients
      received co-medication with pantoprazole; 13 patients received no treatment with
      PPIs or antacids. To assess the immunosuppressive potency, we measured
      mycophenolic acid levels and inosin monophosphate dehydrogenase (IMPDH) activity
      with a validated HPLC method in plasma samples collected pre-dose and at 0.5, 1,
      1.5, 2, 3, 4, 5, 6, 8, 10 and 12 h after oral administration. RESULTS: The mean
      MMF dosage of the non-PPI patients was 770 (249) mg/12 h and 771 (291) mg/12 h in
      pantoprazole-treated patients (NS). The total area under the curve of MMF showed
      a 37% reduction in PPI patients vs those treated with no PPIs (P < 0.01), and the
      maximum peak concentration of MMF was 60% lower in the pantoprazole patients (P <
      0.001). The MMF exposure correlated with the inhibition of IMPDH activity. The
      area of enzyme activity curve was 42% higher in the PPI patients (P < 0.01).
      CONCLUSIONS: The co-medication of pantoprazole with MMF significantly influences
      the drug exposure and immunosuppressive potency of MMF in patients with
      autoimmune diseases. This finding might at least partly explain the different
      outcomes in studies using MMF for maintenance therapy.

PMID- 20671024
TI  - Polychlorinated biphenyls and polybrominated diphenyl ethers alter striatal
      dopamine neurochemistry in synaptosomes from developing rats in an additive
      manner.
AB  - Polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) are
      widespread environmental contaminants associated with changes in behavior and
      neurochemical function in laboratory animals and behavioral deficits in children.
      PCBs and PBDEs are found in food, especially in seafood and dairy products, and
      coexposure to these contaminants is likely. We examined the effects of an
      environmentally relevant mixture of PCBs (Fox River Mix [FRM]) and a PBDE mixture
      (DE-71) alone and in combination on synaptosomal and medium dopamine (DA) levels
      and the levels of the DA metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in
      striatal synaptosomes derived from postnatal days (PND) 7, PND14, or PND21 rats.
      FRM elevated medium DA and reduced synaptosomal DA concentrations with greater
      potency than equimolar concentrations of DE-71. The effects of FRM, but not DE
      71, were dependent on the age of the animals from which the synaptosomes were
      derived, with greater effects observed in synaptosomes from the youngest animals.
      We used Bliss' model of independence to assess the possible interaction(s) of a
      1:1 mixture of FRM and DE-71 on synaptosomal DA function and found that the
      effects of the FRM/DE-71 mixture were additive. Furthermore, as for FRM alone,
      the effects of the FRM/DE71 mixture were greater in synaptosomes prepared from
      PND7 rats than in synaptosomes from PND14 and PND21 rats. Because the effects of
      these contaminants are additive, it is necessary to take into account the
      cumulative exposure to organohalogen contaminants such as PCBs and PBDEs during
      risk assessment.

PMID- 20671025
TI  - Error correction of next-generation sequencing data and reliable estimation of
      HIV quasispecies.
AB  - Next-generation sequencing technologies can be used to analyse genetically
      heterogeneous samples at unprecedented detail. The high coverage achievable with
      these methods enables the detection of many low-frequency variants. However,
      sequencing errors complicate the analysis of mixed populations and result in
      inflated estimates of genetic diversity. We developed a probabilistic Bayesian
      approach to minimize the effect of errors on the detection of minority variants.
      We applied it to pyrosequencing data obtained from a 1.5-kb-fragment of the HIV-1
      gag/pol gene in two control and two clinical samples. The effect of PCR
      amplification was analysed. Error correction resulted in a two- and five-fold
      decrease of the pyrosequencing base substitution rate, from 0.05% to 0.03% and
      from 0.25% to 0.05% in the non-PCR and PCR-amplified samples, respectively. We
      were able to detect viral clones as rare as 0.1% with perfect sequence
      reconstruction. Probabilistic haplotype inference outperforms the counting-based
      calling method in both precision and recall. Genetic diversity observed within
      and between two clinical samples resulted in various patterns of phenotypic drug
      resistance and suggests a close epidemiological link. We conclude that
      pyrosequencing can be used to investigate genetically diverse samples with high
      accuracy if technical errors are properly treated.

PMID- 20671026
TI  - Arrest of human mitochondrial RNA polymerase transcription by the biological
      aldehyde adduct of DNA, M1dG.
AB  - The biological aldehydes, malondialdehyde and base propenal, react with DNA to
      form a prevalent guanine adduct, M(1)dG. The exocyclic ring of M(1)dG opens to
      the acyclic N(2)-OPdG structure when paired with C but remains closed in single
      stranded DNA or when mispaired with T. M(1)dG is a target of nucleotide excision
      repair (NER); however, NER is absent in mitochondria. An in vitro transcription
      system with purified human mitochondrial RNA polymerase (POLRMT) and
      transcription factors, mtTFA and mtTFB2, was used to determine the effect of
      M(1)dG on POLRMT elongation. DNA templates contained a single adduct opposite
      either C or T downstream of either the light-strand (LSP) or heavy-strand (HSP1)
      promoter for POLRMT. M(1)dG in the transcribed strand arrested 60-90% POLRMT
      elongation complexes with greater arrest by the adduct when opposite T. POLRMT
      was more sensitive to N(2)-OPdG and M(1)dG after initiation at LSP, which
      suggests promoter-specific differences in the function of POLRMT complexes. A
      closed-ring analog of M(1)dG, PdG, blocked >=95% of transcripts originating from
      either promoter regardless of base pairing, and the transcripts remained
      associated with POLRMT complexes after stalling at the adduct. This work suggests
      that persistent M(1)dG adducts in mitochondrial DNA hinder the transcription of
      mitochondrial genes.

PMID- 20671027
TI  - A two-parameter generalized Poisson model to improve the analysis of RNA-seq
      data.
AB  - Deep sequencing of RNAs (RNA-seq) has been a useful tool to characterize and
      quantify transcriptomes. However, there are significant challenges in the
      analysis of RNA-seq data, such as how to separate signals from sequencing bias
      and how to perform reasonable normalization. Here, we focus on a fundamental
      question in RNA-seq analysis: the distribution of the position-level read counts.
      Specifically, we propose a two-parameter generalized Poisson (GP) model to the
      position-level read counts. We show that the GP model fits the data much better
      than the traditional Poisson model. Based on the GP model, we can better estimate
      gene or exon expression, perform a more reasonable normalization across different
      samples, and improve the identification of differentially expressed genes and the
      identification of differentially spliced exons. The usefulness of the GP model is
      demonstrated by applications to multiple RNA-seq data sets.

PMID- 20671028
TI  - Deconstructing nucleotide binding activity of the Mdm2 RING domain.
AB  - Mdm2, a central negative regulator of the p53 tumor suppressor, possesses a
      Really Interesting New Gene (RING) domain within its C-terminus. In addition to
      E3 ubiquitin ligase activity, the Mdm2 RING preferentially binds adenine base
      nucleotides, and such binding leads to a conformational change in the Mdm2 C
      terminus. Here, we present further biochemical analysis of the nucleotide-Mdm2
      interaction. We have found that MdmX, an Mdm2 family member with high sequence
      homology, binds adenine nucleotides with similar affinity and specificity as
      Mdm2, suggesting that residues involved in nucleotide binding may be conserved
      between the two proteins and adenosine triphosphate (ATP) binding may have
      similar functional consequences for both Mdm family members. By generating and
      testing a series of proteins with deletions and substitution mutations within the
      Mdm2 RING, we mapped the specific adenine nucleotide binding region of Mdm2 to
      residues 429-484, encompassing the minimal RING domain. Using a series of ATP
      derivatives, we demonstrate that phosphate coordination by the Mdm2 P-loop
      contributes to, but is not primarily responsible for, ATP binding. Additionally,
      we have identified the 2' and 3' hydroxyls of the ribose and the C6 amino group
      of the adenine base moiety as being essential for binding.

PMID- 20671029
TI  - Cooperative translocation enhances the unwinding of duplex DNA by SARS
      coronavirus helicase nsP13.
AB  - SARS coronavirus encodes non-structural protein 13 (nsP13), a nucleic acid
      helicase/NTPase belonging to superfamily 1 helicase, which efficiently unwinds
      both partial-duplex RNA and DNA. In this study, unwinding of DNA substrates that
      had different duplex lengths and 5'-overhangs was examined under single-turnover
      reaction conditions in the presence of excess enzyme. The amount of DNA unwound
      decreased significantly as the length of the duplex increased, indicating a poor
      in vitro processivity. However, the quantity of duplex DNA unwound increased as
      the length of the single-stranded 5'-tail increased for the 50-bp duplex. This
      enhanced processivity was also observed for duplex DNA that had a longer single
      stranded gap in between. These results demonstrate that nsP13 requires the
      presence of a long 5'-overhang to unwind longer DNA duplexes. In addition,
      enhanced DNA unwinding was observed for gapped DNA substrates that had a 5'
      overhang, indicating that the translocated nsP13 molecules pile up and the
      preceding helicase facilitate DNA unwinding. Together with the propensity of
      oligomer formation of nsP13 molecules, we propose that the cooperative
      translocation by the functionally interacting oligomers of the helicase molecules
      loaded onto the 5'-overhang account for the observed enhanced processivity of DNA
      unwinding.

PMID- 20671030
TI  - Genomic analysis of codon, sequence and structural conservation with selective
      biochemical-structure mapping reveals highly conserved and dynamic structures in
      rotavirus RNAs with potential cis-acting functions.
AB  - Rotaviruses are a major cause of acute, often fatal, gastroenteritis in infants
      and young children world-wide. Virions contain an 11 segment double-stranded RNA
      genome. Little is known about the cis-acting sequences and structural elements of
      the viral RNAs. Using a database of 1621 full-length sequences of mammalian group
      A rotavirus RNA segments, we evaluated the codon, sequence and RNA structural
      conservation of the complete genome. Codon conservation regions were found in
      eight ORFs, suggesting the presence of functional RNA elements. Using ConStruct
      and RNAz programmes, we identified conserved secondary structures in the positive
      sense RNAs including long-range interactions (LRIs) at the 5' and 3' terminal
      regions of all segments. In RNA9, two mutually exclusive structures were observed
      suggesting a switch mechanism between a conserved terminal LRI and an independent
      3' stem-loop structure. In RNA6, a conserved stem-loop was found in a region
      previously reported to have translation enhancement activity. Biochemical
      structural analysis of RNA11 confirmed the presence of terminal LRIs and two
      internal helices with high codon and sequence conservation. These extensive in
      silico and in vitro analyses provide evidence of the conservation, complexity,
      multi-functionality and dynamics of rotavirus RNA structures which likely
      influence RNA replication, translation and genome packaging.

PMID- 20671031
TI  - The phosphatase interactor NIPP1 regulates the occupancy of the histone
      methyltransferase EZH2 at Polycomb targets.
AB  - Polycomb group (PcG) proteins are key regulators of stem-cell and cancer biology.
      They mainly act as repressors of differentiation and tumor-suppressor genes. One
      key silencing step involves the trimethylation of histone H3 on Lys27 (H3K27) by
      EZH2, a core component of the Polycomb Repressive Complex 2 (PRC2). The mechanism
      underlying the initial recruitment of mammalian PRC2 complexes is not well
      understood. Here, we show that NIPP1, a regulator of protein Ser/Thr phosphatase
      1 (PP1), forms a complex with PP1 and PRC2 components on chromatin. The knockdown
      of NIPP1 or PP1 reduced the association of EZH2 with a subset of its target
      genes, whereas the overexpression of NIPP1 resulted in a retargeting of EZH2 from
      fully repressed to partially active PcG targets. However, the expression of a PP1
      binding mutant of NIPP1 (NIPP1m) did not cause a redistribution of EZH2.
      Moreover, mapping of the chromatin binding sites with the DamID technique
      revealed that NIPP1 was associated with multiple PcG target genes, including the
      Homeobox A cluster, whereas NIPP1m showed a deficient binding at these loci. We
      propose that NIPP1 associates with a subset of PcG targets in a PP1-dependent
      manner and thereby contributes to the recruitment of the PRC2 complex.

PMID- 20671032
TI  - Arterial stiffening following eccentric exercise-induced muscle damage.
AB  - Acute inflammatory responses are linked to a transient increase in risk of a
      cardiovascular event, and this risk may be mediated by a concomitant reduction in
      vascular function. Humans experience an acute inflammatory response as a
      consequence of infection, injury, or muscle damage. We measured macrovascular
      function before and after eccentric exercise to determine whether muscle damage
      from unaccustomed exercise has an unfavorable effect on the large elastic
      arteries. A total of 27 healthy sedentary or recreationally active men (age 18-38
      years) participated in either bilateral leg press eccentric exercise or
      unilateral elbow flexor eccentric exercise. Postexercise muscle damage was
      confirmed by significant reductions in isometric strength and increases in muscle
      soreness (P < 0.05). Carotid-femoral pulse-wave velocity was significantly
      elevated 48 h after leg exercise (808 +/- 31 vs. 785 +/- 30 cm/s; P < 0.05) and
      arm exercise (790 +/- 28 vs. 755 +/- 24 cm/s; P < 0.05). There were no changes in
      mean arterial pressure. C-reactive protein was elevated after leg exercise but
      not after arm exercise. The increase in carotid-femoral pulse wave velocity 48 h
      after arm exercise was associated with muscle strength (r = -0.47; P < 0.05) and
      creatine kinase concentrations (r = 0.70; P < 0.01). We concluded that eccentric
      exercise in both small and large muscle mass translates to transient, unfavorable
      changes in central macrovascular function and that the increase in central
      arterial stiffness after small muscle eccentric exercise is associated with
      indicators of muscle damage.

PMID- 20671033
TI  - Measuring FMD in the brachial artery: how important is QRS gating?
AB  - Recommendations for the measurement of brachial flow-mediated dilation (FMD)
      typically suggest images be obtained at identical times in the cardiac cycle,
      usually end diastole (QRS complex onset). This recommendation presumes that inter
      individual differences in arterial compliance are minimized. However, published
      evidence is conflicting. Furthermore, ECG gating is not available on many
      ultrasound systems; it requires an expensive software upgrade or increased image
      processing time. We tested whether analysis of images acquired with QRS gating or
      with the more simplified method of image averaging would yield similar results.
      We analyzed FMD and nitroglycerin-mediated dilation (NMD) in 29 adults with type
      2 diabetes mellitus and in 31 older adults and 12 young adults without diabetes,
      yielding a range of brachial artery distensibility. FMD and NMD were measured
      using recommended QRS-gated brachial artery diameter measurements and,
      alternatively, the average brachial diameters over the entire R-R interval. We
      found strong agreement between both methods for FMD and NMD (intraclass
      correlation coefficients = 0.88-0.99). Measuring FMD and NMD using average
      diameter measurements significantly reduced post-image-processing time (658.9 +/-
      71.6 vs. 1,024.1 +/- 167.6 s for QRS-gated analysis, P < 0.001). FMD and NMD
      measurements based on average diameter measurements can be performed without
      reducing accuracy. This finding may allow for simplification of FMD measurement
      and aid in the development of FMD as a potentially useful clinical tool.

PMID- 20671035
TI  - Dynamics of tidal volume and ventilation heterogeneity under pressure-controlled
      ventilation during bronchoconstriction: a simulation study.
AB  - The difference in effectiveness between volume-controlled ventilation (VCV) and
      pressure-controlled ventilation (PCV) on mechanically ventilated patients during
      bronchoconstriction is not totally clear. PCV is thought to deliver a more
      uniform distribution of ventilation than VCV, but the delivered tidal volume
      could be unstable and affected by changes in the degree of constriction. To
      explore the magnitude of these effects, we ran numerical simulations with both
      modes of ventilation in a network model of the lung in which we incorporated not
      only the pressure and flow dynamics along the airways but also the effect of
      cycling pressures and tissue tethering forces during breathing on the dynamic
      equilibrium of the airway smooth muscle (ASM) (Venegas et al., Nature 434: 777
      782). These simulations provided an illustration of changes in airway radii, the
      total delivered tidal volume stability, and distribution of ventilation following
      a transition from VCV to PCV and during progressively increasing ASM activation
      level. These simulations yielded three major results. First, the ventilation
      heterogeneity and patchiness in ventilation during steady-state VCV were
      substantially reduced after the transition to PCV. Second, airway radius, tidal
      volume, and the distribution of ventilation under severe bronchoconstriction were
      highly sensitive to the setting of inspiratory pressure selected for PCV and to
      the degree of activation of the ASM. Third, the dynamic equilibrium of active ASM
      exposed to cycling forces is the major contributor to these effects. These
      insights may provide a theoretical framework to guide the selection of
      ventilation mode, the adjustment of ventilator settings, and the interpretation
      of clinical observations in mechanically ventilated asthmatic patients.

PMID- 20671034
TI  - Thermoregulation in multiple sclerosis.
AB  - Multiple sclerosis (MS) is a progressive neurological disorder that disrupts
      axonal myelin in the central nervous system. Demyelination produces alterations
      in saltatory conduction, slowed conduction velocity, and a predisposition to
      conduction block. An estimated 60-80% of MS patients experience temporary
      worsening of clinical signs and neurological symptoms with heat exposure.
      Additionally, MS may produce impaired neural control of autonomic and endocrine
      functions. This review focuses on five main themes regarding the current
      understanding of thermoregulatory dysfunction in MS: 1) heat sensitivity; 2)
      central regulation of body temperature; 3) thermoregulatory effector responses;
      4) heat-induced fatigue; and 5) countermeasures to improve or maintain function
      during thermal stress. Heat sensitivity in MS is related to the detrimental
      effects of increased temperature on action potential propagation in demyelinated
      axons, resulting in conduction slowing and/or block, which can be quantitatively
      characterized using precise measurements of ocular movements. MS lesions can also
      occur in areas of the brain responsible for the control and regulation of body
      temperature and thermoregulatory effector responses, resulting in impaired neural
      control of sudomotor pathways or neural-induced changes in eccrine sweat glands,
      as evidenced by observations of reduced sweating responses in MS patients.
      Fatigue during thermal stress is common in MS and results in decreased motor
      function and increased symptomatology likely due to impairments in central
      conduction. Although not comprehensive, some evidence exists concerning
      treatments (cooling, precooling, and pharmacological) for the MS patient to
      preserve function and decrease symptom worsening during heat stress.

PMID- 20671036
TI  - Lung structure phenotype variation in inbred mouse strains revealed through in
      vivo micro-CT imaging.
AB  - Within pulmonary research, the development of mouse models has provided insight
      into disease development, progression, and treatment. Structural phenotypes of
      the lung in healthy inbred mouse strains are necessary for comparison to disease
      models. To date, progress in the assessment of lung function in these small
      animals using whole lung function tests has been made. However, assessment of in
      vivo lung structure of inbred mouse strains has yet to be well defined.
      Therefore, the link between the structure and function phenotypes is still
      unclear. With advancements in small animal imaging it is now possible to
      investigate lung structures such as the central and peripheral airways, whole
      lung, and lobar volumes of mice in vivo, through the use of micro-CT imaging. In
      this study, we performed in vivo micro-CT imaging of the C57BL/6, A/J, and BALB/c
      mouse strains using the intermittent iso-pressure breath hold (IIBH) technique.
      The resulting high-resolution images were used to extract lung structure
      phenotypes. The three-dimensional lobar structures and airways were defined and a
      meaningful mouse airway nomenclature was developed. In addition, using these
      techniques we have uncovered significant differences in the airway structures
      between inbred mouse strains in vivo.

PMID- 20671037
TI  - Lung volume and pharyngeal stability in sleeping humans: the knee bone is
      connected to the thigh bone.

PMID- 20671038
TI  - Important role of muscle carnosine in rowing performance.
AB  - The role of the presence of carnosine (beta-alanyl-L-histidine) in millimolar
      concentrations in human skeletal muscle is poorly understood. Chronic oral beta
      alanine supplementation is shown to elevate muscle carnosine content and improve
      anaerobic exercise performance during some laboratory tests, mainly in the
      untrained. It remains to be determined whether carnosine loading can improve
      single competition-like events in elite athletes. The aims of the present study
      were to investigate if performance is related to the muscle carnosine content and
      if beta-alanine supplementation improves performance in highly trained rowers.
      Eighteen Belgian elite rowers were supplemented for 7 wk with either placebo or
      beta-alanine (5 g/day). Before and following supplementation, muscle carnosine
      content in soleus and gastrocnemius medialis was measured by proton magnetic
      resonance spectroscopy ((1)H-MRS) and the performance was evaluated in a 2,000-m
      ergometer test. At baseline, there was a strong positive correlation between 100
      , 500-, 2,000-, and 6,000-m speed and muscle carnosine content. After beta
      alanine supplementation, the carnosine content increased by 45.3% in soleus and
      28.2% in gastrocnemius. Following supplementation, the beta-alanine group was 4.3
      s faster than the placebo group, whereas before supplementation they were 0.3 s
      slower (P = 0.07). Muscle carnosine elevation was positively correlated to 2,000
      m performance enhancement (P = 0.042 and r = 0.498). It can be concluded that the
      positive correlation between baseline muscle carnosine levels and rowing
      performance and the positive correlation between changes in muscle carnosine and
      performance improvement suggest that muscle carnosine is a new determinant of
      rowing performance.

PMID- 20671039
TI  - Approximating model probabilities in Bayesian information criterion and decision
      theoretic approaches to model selection in phylogenetics.
AB  - A priori selection of models for use in phylogeny estimation from molecular
      sequence data is increasingly important as the number and complexity of available
      models increases. The Bayesian information criterion (BIC) and the derivative
      decision-theoretic (DT) approaches rely on a conservative approximation to
      estimate the posterior probability of a given model. Here, we extended the DT
      method by using reversible jump Markov chain Monte Carlo approaches to directly
      estimate model probabilities for an extended candidate pool of all 406 special
      cases of the general time reversible + Gamma family. We analyzed 250 diverse data
      sets in order to evaluate the effectiveness of the BIC approximation for model
      selection under the BIC and DT approaches. Model choice under DT differed between
      the BIC approximation and direct estimation methods for 45% of the data sets
      (113/250), and differing model choice resulted in significantly different sets of
      trees in the posterior distributions for 26% of the data sets (64/250). The model
      with the lowest BIC score differed from the model with the highest posterior
      probability in 30% of the data sets (76/250). When the data indicate a clear
      model preference, the BIC approximation works well enough to result in the same
      model selection as with directly estimated model probabilities, but a substantial
      proportion of biological data sets lack this characteristic, which leads to
      selection of underparametrized models.

PMID- 20671040
TI  - Whole-genome expression plasticity across tropical and temperate Drosophila
      melanogaster populations from Eastern Australia.
AB  - The genotypic signature of spatially varying selection is ubiquitous across the
      Drosophila melanogaster genome. Spatially structured adaptive phenotypic
      differences are also commonly found, particularly along New World and Australian
      latitudinal gradients. However, investigation of gene expression variation in one
      or multiple environments across these well-studied populations is surprisingly
      limited. Here, we report genome-wide transcript levels of tropical and temperate
      eastern Australian populations reared at two temperatures. As expected, a large
      number of genes exhibit geographic origin-dependent expression plasticity. Less
      expected was evidence for an enrichment of down-regulated genes in both temperate
      and tropical populations when lines were reared at the temperature less commonly
      encountered in the native range; that is, evidence for significant differences in
      a "directionality" of plasticity across these two climatic regions. We also
      report evidence of small scale "neighborhood effects" around those genes
      significant for geographic origin-dependent plasticity, a result consistent with
      the evolution of high level, likely chromatin based gene regulation during range
      expansion in D. melanogaster populations.

PMID- 20671041
TI  - Impact of indels on the flanking regions in structural domains.
AB  - Amino acid substitution and insertions/deletions (indels) are two common events
      in protein evolution; however, current knowledge on indels is limited. In this
      study, we investigated the effects of indels on the flanking regions in protein
      structure superfamilies. Comprehensive analysis of structural classification of
      proteins superfamilies revealed that indels lead to a series of changes in the
      flanking regions, including the following: 1) structural shift in the tertiary
      structure, with a first-order exponential decay relation between structural shift
      and the distance to indels, 2) instability of the secondary structure elements in
      which parts of the alpha helix and beta sheet are destroyed, and 3) an increase
      in the amino acid substitution rate of the primary structure and the nonsimilar
      amino acid substitution rate. In general, these quality changes are due to the
      combined effects of the "regional-inherent effect," "indel-accompanied effect,"
      and "indel-following effect." Furthermore, these quality changes reflect changes
      in selective pressure. Indels are more likely to be preserved in regions with low
      selective pressure, and indels can further reduce the selective pressure on the
      flanking regions. These findings improve our understanding of the role of indels
      in protein evolution.

PMID- 20671042
TI  - Enteropathy-associated T cell lymphoma of the jejunum associated with colonic
      lymphocytosis with aberrant phenotype.

PMID- 20671043
TI  - A case of intravascular myopericytoma.

PMID- 20671044
TI  - Churg-Strauss syndrome manifested by appendicitis, cholecystitis and superficial
      micronodular liver lesions--an unusual clinicopathological presentation.

PMID- 20671045
TI  - Spontaneous bacterial peritonitis due to Listeria monocytogenes: importance of
      enrichment culture.
AB  - A case of Listeria monocytogenes induced spontaneous bacterial peritonitis (SBP)
      is reported in a patient with primary biliary cirrhosis. It is an indolent
      illness and may not show a neutrophil reaction in peritoneal fluid. Enrichment
      broth was required to isolate L monocytogenes in the patient. This is not
      routinely used in the UK and therefore isolates may be missed. L monocytogenes
      remains sensitive to ampicillin, penicillin and gentamicin, but is resistant to
      cephalosporin antibiotics. The rising incidence of listeriosis in the population
      suggests that the incidence of SBP from L monocytogenes is likely to increase.

PMID- 20671046
TI  - Elevated D-dimers are also a marker of underlying malignancy and increased
      mortality in the absence of venous thromboembolism.
AB  - BACKGROUND: D-dimers are used in conjunction with clinical probability scores in
      the assessment of venous thromboembolism (VTE), and they are elevated in other
      conditions, including malignancy, infection and arrhythmias. High levels of D
      dimers in VTE are associated with adverse outcomes, including increased
      mortality. Their significance in patients without VTE has not previously been
      established. AIMS: To establish the clinical significance of elevated D-dimer
      levels in patients without VTE. METHODS: This prospective study included 2263
      patient episodes of suspected deep vein thrombosis, which were excluded
      radiologically. Patients were followed up for survival and adverse events for a
      median of 22 months. RESULTS: D-dimer levels greater than 4000 ng FEU/ml (4.9% of
      patients), and greater than 8000 ng FEU/ml (1.8%) were associated with a reduced
      overall survival. D-dimer levels greater than 8000 ng FEU/ml and age over 60
      years were independent poor prognostic factors for overall survival (p<0.001.). D
      dimer levels greater than 8000 ng FEU/ml were associated with an increased
      incidence of malignancy (p=0.003). CONCLUSIONS: This study provides evidence of
      very high D-dimer levels in patients with cancer who do not have VTE. This
      suggests that elevated D-dimer levels in patients with VTE and malignancy are not
      solely due to presence of thrombus. High D-dimer levels in malignancy are likely
      to reflect the biology of the underlying tumour, with higher levels observed in
      breast, prostate and bowel cancers.

PMID- 20671047
TI  - Lymphoma occurring in patients with cutaneous melanoma.
AB  - BACKGROUND: Non-melanoma malignancies are not uncommon in patients with melanoma.
      This study sought to determine the incidence of lymphoma in patients with
      melanoma compared with the general population, and to characterise their clinical
      and pathological features. METHODS: Patients diagnosed with melanoma and lymphoma
      between January 1992 and December 2007 were identified from the databases of
      Melanoma Institute Australia (MIA) and the Department of Tissue Pathology and
      Diagnostic Oncology, Royal Prince Alfred Hospital (RPAH). The clinical histories
      of the patients in the MIA database and pathology reports in the RPAH archives
      were reviewed. The incidence risk for melanoma and non-Hodgkin lymphoma was
      obtained from Australian Cancer Incidence and Mortality registry data. RESULTS:
      Of 18,226 patients with melanoma, 55 (0.3%) had lymphoma. Lymphoma was diagnosed
      subsequent to melanoma in 23 (41.8%) patients, prior to melanoma in 7 (12.7%)
      patients, and concurrently with melanoma in 25 (45.5%) patients. 53 (96.4%)
      patients developed non-Hodgkin lymphoma (NHL), the most common subtypes being
      chronic lymphocytic leukaemia/small lymphocytic lymphoma (49.1%), follicular
      lymphoma (23.6%) and diffuse large B-cell lymphoma (16.4%). Two (3.6%) patients
      developed Hodgkin lymphoma. Melanoma patients had a significantly higher risk of
      developing NHL than the general population (standardised incidence rate 3.5).
      CONCLUSIONS: A small but significant proportion of patients with melanoma develop
      lymphoma, either synchronously or metachronously. Lymph node specimens from
      melanoma patients might harbour lymphoma, and might represent the first
      recognised site of disease. A high index of suspicion for lymphoma when
      evaluating lymph nodes from patients with melanoma will ensure prompt diagnosis
      and appropriate management.

PMID- 20671048
TI  - Surface bacteriology of venous leg ulcers and healing outcome.
AB  - AIM: Bacteria can be cultured from all venous leg ulcers (VLUs) regardless of
      healing status, and the significance of a positive swab result in non-clinically
      infected ulcers is unknown. The aim of this study was to characterise the
      bacteriological flora of VLUs by routine culture to determine whether the data
      generated had prognostic value. METHODS: The ulcers of 178 patients were sampled
      weekly for 12 weeks and healing outcome monitored while the limb was treated with
      graduated compression. Wound bacteriology was assessed using culture methodology
      standardised to ensure data reproducibility. RESULTS: 153 individual bacterial
      species were identified. The species most frequently found were Staphylococcus
      aureus (64.3% of assessments), Corynebacterium striatum (60.6%), Pseudomonas
      aeruginosa (32.6%), Helcococcus kunzii (22.0%), Finegoldia magna (21.4%) and
      Proteus mirabilis (16.1%). No single species or the presence of anaerobes and
      increasing diversity of bacterial species, previously thought to be predictive of
      impaired healing, was shown to be associated with healing outcome. The presence
      of C striatum was associated with healing outcome but not after adjusting for the
      known prognostic factors of wound area and duration. CONCLUSION: Routine
      bacteriological culture analysis of the VLU wound surface may be used to identify
      diverse flora in all ulcers. However, the data generated are of no additional
      value as a prognostic indicator of healing outcome. The presence of C striatum
      may represent colonisation of non-healing VLU by normal skin flora.

PMID- 20671049
TI  - Self-administered hyaluronidase-facilitated subcutaneous immunoglobulin home
      therapy in a patient with primary immunodeficiency.

PMID- 20671050
TI  - Mesothelial/monocytic incidental cardiac excrescences (MICE) with tubercular
      aortitis: report of the first case with brief review of the literature.

PMID- 20671051
TI  - Methylation of TET2, CBL and CEBPA in Ph-negative myeloproliferative neoplasms.
AB  - A loss-of-function mutation of TET2, CBL and CEBPA has been implicated in the
      pathogenesis or leukaemic transformation of myeloproliferative neoplasm. As
      tumour suppressor genes may potentially be inactivated by promoter
      hypermethylation, the authors studied the methylation status of these genes in
      three cell lines and diagnostic marrow samples from 45 patients with
      myeloproliferative neoplasm (MPN) (essential thrombocythaemia, N=34;
      polycythaemia vera, N=7 and primary myelofibrosis, N=4) by methylation-specific
      PCR. TET2 was heterozygously methylated in MEG-01 and K562 but completely
      unmethylated in HEL. On the other hand, both CBL and CEBPA were completely
      unmethylated in all three cell lines. In the primary marrow samples, methylation
      of TET2 occurred in two (5.9%) patients with essential thrombocythaemia (4.4% of
      all patients), both without JAK2 V617 mutation, but not in polycythaemia vera or
      primary myelofibrosis. There was no association between TET2 methylation with the
      type of MPN (p=0.713). Hypermethylation of CBL or CEBPA was not detected in any
      patients. In summary, methylation of TET2, CBL and CEBPA is infrequent in MPN at
      diagnosis. The role of methylation of these genes at the time of leukaemic
      transformation warrants further study.

PMID- 20671052
TI  - Comparative validation of the SP6 antibody to Ki67 in breast cancer.
AB  - AIM: To compare SP6 and MIB1 antibodies for Ki67 staining in breast cancer.
      BACKGROUND: Immunohistochemical detection of Ki67 has been widely used to assess
      the proliferative fraction in breast cancer. Ki67 is used prognostically and is
      the primary end-point for some presurgical trials. MIB1 has been the preferred
      antibody, but SP6 has become available, with apparently improved performance. The
      importance of Ki67 led us to systematically compare SP6 with MIB1. METHODS: Two
      sets of tissue microarrays were used. These were constructed from formalin-fixed
      paraffin-embedded breast cancers: (i) 177 cancers with data on response to an
      aromatase inhibitor for advanced disease (cohort 1); (ii) 200 mainly oestrogen
      receptor-positive cancers without response data (cohort 2). Twenty-eight pairs of
      core-cut biopsies taken before and after aromatase inhibitor treatment were also
      assessed (cohort 3). Stained sections were examined either visually or by using
      an image analysis system (Ariol). RESULTS: There was a strong correlation between
      the two antibodies in all cohorts of samples scored visually (cohort 1: n=161,
      r=0.93, p<0.0001; cohort 2: n=194, r=0.84, p<0.0001; cohort 3: n=54, r=0.89,
      p<0.0001). Correlation between visual and Ariol scores was markedly better with
      the SP6 antibody (r=0.71 and r=0.88 for MIB1 and SP6, respectively). Ki67 related
      similarly with time-to-treatment failure with the two antibodies (cohort 1).
      Changes in Ki67 values with the two antibodies after 2 weeks of aromatase
      inhibitor treatment also correlated strongly. CONCLUSIONS: SP6 and MIB1 provide
      highly comparable measures of Ki67 that predict progression of advanced disease
      similarly. SP6 is substantially better suited than MIB1 to image analysis.

PMID- 20671053
TI  - The Poor Man's Cell Block.
AB  - The authors describe a simple method for making formalin or isopropyl alcohol
      vapour fixed cell blocks from fine needle aspiration cytology specimens that we
      refer to as 'The Poor Man's Cell Block.'

PMID- 20671054
TI  - The evolution of melanoma diagnosis: 25 years beyond the ABCDs.
AB  - Early detection of malignant melanoma remains the key factor in lowering
      mortality from this cancer. Recognizing the importance of this issue 25 years
      ago, our group at New York University published in CA: A Cancer Journal for
      Clinicians the mnemonic "ABCD" to facilitate the early diagnosis of melanoma.
      Studies have demonstrated the usefulness of this paradigm in enhancing early
      melanoma diagnosis as a part of clinical examinations, mass screenings, and
      public education programs. Approaches to melanoma diagnosis have dynamically
      evolved during the ensuing quarter century. In the 1990s, dermoscopy enabled the
      recognition of new subsurface features to differentiate between malignant and
      benign pigmented lesions. During the last decade, new computer-based technologies
      have improved diagnostic sensitivity and specificity and may result in optimizing
      lesion selection for biopsy and pathology review. Despite all of the advances in
      melanoma diagnosis, timely recognition, detection, and rapid treatment of
      melanoma remain critical. Although pathologic examination remains the gold
      standard for diagnosis, this cancer has the potential to be diagnosed through
      noninvasive approaches because of its cutaneous location. From the development of
      the ABCDs through current attempts that use complex computer algorithms and
      genetic markers, a clinician's ability to detect melanoma in its earliest form
      has been augmented. However, a "good clinical eye" is still fundamental to
      selecting the lesions for evaluation among the sea of those that are prevalent.
      As current approaches are refined and new techniques are developed, the improved
      ability to diagnose this cancer will hopefully enhance reaching the goal of
      reducing melanoma mortality.

PMID- 20671055
TI  - Mucins carrying selectin ligands as predictive biomarkers of disseminated
      intravascular coagulation complication in ARDS.
AB  - BACKGROUND: ARDS patients present with intrapulmonary and systemic coagulation
      abnormalities. We previously demonstrated that circulating KL-6/MUC1 could
      predict complications of disseminated intravascular coagulation (DIC) in ARDS.
      Recent studies indicate that circulating mucin can induce intravascular
      coagulation via interactions with selectin. We, therefore, investigated whether
      circulating mucins carrying selectin ligands are associated with DIC in ARDS.
      METHODS: We evaluated newly diagnosed patients with ARDS (n = 46) or bacterial
      pneumonia (n = 17), and healthy control subjects (n = 60). Using serum collected
      at diagnosis, circulating levels of KL-6/MUC1, KL-6/MUC1 carrying sialyl Lewis(a)
      (SLAK), KL-6/MUC1 carrying sialyl Lewis(x) (SLXK), and P-selectin glycoprotein
      ligand-1 (PSGL-1) were measured. RESULTS: Serum mucins with selectin ligands were
      significantly elevated in patients with ARDS compared with healthy control
      subjects. Significantly elevated levels of SLAK and SLXK were found in patients
      with ARDS subsequently complicated with DIC, as compared with those without DIC.
      In contrast, serum PSGL-1 levels were significantly decreased in ARDS patients
      with DIC. Furthermore, SLAK was discovered to be an independent predictor of DIC
      complication in ARDS. Using cutoff levels obtained by receiver operating
      characteristic curves, we found that these mucins can be used to distinguish
      between patients with ARDS with and without subsequently occurring DIC. Among the
      analyzed mucins, SLAK has the highest sensitivity and specificity for predicting
      future DIC development. CONCLUSIONS: These results suggest that mucins with
      selectin ligands are novel markers for ARDS with future complications of DIC, and
      KL-6/MUC1 carrying selectin ligands may be involved in the pathogenesis of DIC in
      patients with ARDS.

PMID- 20671056
TI  - Oximeter-based autonomic state indicator algorithm for cardiovascular risk
      assessment.
AB  - BACKGROUND: Cardiovascular (CV) risk assessment is important in clinical
      practice. An autonomic state indicator (ASI) algorithm based on pulse oximetry
      was developed and validated for CV risk assessment. METHODS: One hundred forty
      eight sleep clinic patients (98 men, mean age 50 +/- 13 years) underwent an
      overnight study using a novel photoplethysmographic sensor. CV risk was
      classified according to the European Society of Hypertension/European Society of
      Cardiology (ESH/ESC) risk factor matrix. Five signal components reflecting
      cardiac and vascular activity (pulse wave attenuation, pulse rate acceleration,
      pulse propagation time, respiration-related pulse oscillation, and oxygen
      desaturation) extracted from 99 randomly selected subjects were used to train the
      classification algorithm. The capacity of the algorithm for CV risk prediction
      was validated in 49 additional patients. RESULTS: Each signal component
      contributed independently to CV risk prediction. The sensitivity and specificity
      of the algorithm to distinguish high/low CV risk in the validation group were 80%
      and 77%, respectively. The area under the receiver operating characteristic curve
      for high CV risk classification was 0.84. beta-Blocker treatment was identified
      as an important factor for classification that was not in line with the ESH/ESC
      reference matrix. CONCLUSIONS: Signals derived from overnight oximetry recording
      provide a novel potential tool for CV risk classification. Prospective studies
      are warranted to establish the value of the ASI algorithm for prediction of
      outcome in CV disease.

PMID- 20671057
TI  - Effects of water-pipe smoking on lung function: a systematic review and meta
      analysis.
AB  - BACKGROUND: Although common in many Middle Eastern countries, water-pipe tobacco
      smoking, commonly known as water-pipe smoking (WPS), is increasingly popular in
      Western cultures. The primary objective of this study was to systematically
      review the effects of WPS on lung function. The secondary objective was to
      compare the effects of WPS and cigarette smoking on lung function. METHODS: We
      conducted a systematic review using the approach of the Cochrane Collaboration to
      search for, select, and abstract studies. We conducted two separate meta-analyses
      comparing water-pipe smokers with nonsmokers, and water-pipe smokers with
      cigarette smokers for each of three spirometric measurements (FEV1, FVC, and
      FEV1/ FVC). We used the standardized mean difference (SMD) to pool the results.
      RESULTS: Six cross-sectional studies were eligible for this review. Compared with
      no smoking, WPS was associated with a statistically significant reduction in FEV1
      (SMD = -0.43; 95% CI, -0.58 to -0.29; equivalent to a 4.04% lower FEV1%), a trend
      toward lower FVC (SMD = -0.15; 95% CI, -0.34 to 0.04; equivalent to a 1.38%
      reduction in FVC%), and lower FEV1/ FVC (SMD = -0.46; 95% CI, -0.93 to 0.01;
      equivalent to a 3.08% lower FEV1/ FVC). Comparing WPS with cigarette smoking,
      there was no statistically significant difference in FEV1, FVC, and FEV1/ FVC.
      The six studies suffered from methodologic limitations. CONCLUSIONS: WPS
      negatively affects lung function and may be as harmful as cigarette smoking. WPS,
      therefore, is likely to be a cause of COPD.

PMID- 20671058
TI  - Inflammatory subtypes in cough-variant asthma: association with maintenance doses
      of inhaled corticosteroids.
AB  - BACKGROUND: Sputum cell-subtype profiles in cough-variant asthma (CVA) are
      unknown. METHODS: Ninety-eight inhaled corticosteroid (ICS)-naive CVA patients
      were classified according to sputum eosinophil (eos)/neutrophil (neu) counts, as
      reported in subjects with asthma, as eosinophilic (E) (eos >= 1.0%, neu < 61%; n
      = 28), neutrophilic (N) (eos < 1.0%, neu >= 61%; n = 31), mixed granulocytic (M)
      (eos >= 1.0%, neu >= 61%; n = 12), and paucigranulocytic (P) (eos < 1.0%, neu <
      61%; n = 27) subtypes. Patient characteristics; sputum levels of eosinophil
      cationic protein (ECP), IL-8, and neutrophil elastase (NE); and daily ICS doses
      required to maintain control during follow-up (6, 12, 18, and 24 months) were
      compared, retrospectively. RESULTS: Subtype N patients, predominantly women, were
      marginally older than the other subtypes, but FEV(1), airway responsiveness, and
      total and specific IgE results did not differ. ECP levels were higher in M and E
      than in N and P subtypes, being similar between M and E or N and P subtypes.
      Levels of IL-8 and NE were higher in M than in other subtypes, being similar
      among the latter. ICS doses were initially similar in all subtypes (800 MUg
      equivalent of beclomethasone) but were higher in M than in N and P subtypes
      throughout follow-up, with E being intermediate between M and N or P subtypes.
      ICS doses decreased (halved or quartered) in E, N, and P patients followed for 24
      months (P < .0001 for all) but remained unchanged in M subjects. IL-8 and NE
      levels correlated positively with ECP levels. CONCLUSIONS: In addition to
      eosinophils, neutrophils, which are possibly activated in the presence of
      eosinophils, may participate in the pathophysiology of CVA.

PMID- 20671059
TI  - Right ventricular load at exercise is a cause of persistent exercise limitation
      in patients with normal resting pulmonary vascular resistance after pulmonary
      endarterectomy.
AB  - BACKGROUND: Pulmonary endarterectomy (PEA) provides a potential cure for patients
      with chronic thromboembolic pulmonary hypertension (CTEPH). However, successfully
      operated patients can continue to suffer from a limitation of exercise capacity,
      despite normalization of pulmonary vascular resistance (PVR). The purpose of the
      present study was to explore the cardiopulmonary exercise test (CPET) profile and
      the pulmonary hemodynamic response to exercise in these patients. METHODS:
      Thirteen successfully operated patients with CTEPH and persistent dyspnea and
      control subjects underwent a CPET and a right-sided heart catheterization at rest
      and during exercise. RESULTS: The CPET profile of the patients was characterized
      by mild hyperventilation and decreased peak oxygen uptake (VO2). While there were
      no differences in resting hemodynamics between patients and control subjects, PVR
      was higher in the patients after 10 min of exercise (111 +/- 46 dynes/s/cm(5) vs
      71 +/- 42 dynes/s/cm(5), P = .04), and pulmonary arterial compliance (Ca) was
      lower (5.5 +/- 2.3 mL/mm Hg vs 8.1 +/- 3.5 mL/mm Hg, P = .048). Ca under exercise
      correlated with peak VO2 in the patients (R(2) = 0.825, P = .022). CONCLUSIONS:
      After successful PEA, patients with persistent exertional dyspnea display an
      abnormal pulmonary hemodynamic response to exercise, characterized by increased
      PVR and decreased Ca. Decreased Ca under exercise is a strong predictor of
      limited exercise capacity in these patients.

PMID- 20671060
TI  - Intracranial stenting in patients with atherosclerotic stenosis associated with
      various aneurysms in the same diseased arterial segment.
AB  - BACKGROUND AND PURPOSE: Aneurysms are rarely associated with symptomatic
      intracranial stenosis. We report the results of recanalization by stent placement
      in patients with symptomatic severe intracranial stenosis associated with
      adjacent aneurysms. MATERIALS AND METHODS: Of 139 patients who underwent
      intracranial stent placement during a 5-year period, 10 (7%) had symptomatic
      severe intracranial stenosis associated with adjacent aneurysms. Five were in the
      VA, 3 in the BA, and 2 in M1. The types of aneurysm were atherosclerotic fusiform
      (n = 5), ulcerative (n = 4), and saccular (n = 1). We analyzed angiographic
      findings based on biplane and 3D angiograms and assessed patient outcomes and
      complications after stent placement. The results were compared with those of a
      control group without aneurysms who underwent stent placement during the same
      study period. RESULTS: Aneurysm locations were post- (n = 6), in- (n = 2), and
      pre-stenotic (n = 2). After angioplasty with stent placement and/or aneurysm
      embolization, there were no lesion-related strokes or deaths during a median
      follow-up period of 25 months (range, 11-43 months). One patient had asymptomatic
      restenosis. The final mRS score was good (<=2) in all patients. There were no
      statistically significant differences in event or restenosis rates compared with
      the control group. CONCLUSIONS: Adjacent aneurysms were rarely associated with
      severe intracranial stenosis but were more common in the posterior circulation.
      Intracranial stent placement may be performed without additional stroke risk,
      regardless of the type and location of the aneurysm.

PMID- 20671061
TI  - Extensive intracranial juvenile xanthogranulomas.
AB  - JXG is a disorder classified under histiocytosis. It usually affects children and
      commonly presents with skin lesions. Intracranial lesions are uncommon and
      usually solitary. We present the case of a child who had extensive intracranial
      involvement with multiple enhancing solid lesions in the cerebellum, brain stem,
      thalami, and bilateral cerebral hemispheres on MR imaging.

PMID- 20671062
TI  - Fetal MR imaging evidence of prolonged apparent diffusion coefficient decrease in
      fetal death.
AB  - We report 2 fetal MR imaging cases at 22 wkGA with cerebral bright DWI and low
      ADC, 8 and 19 days after documented fetal death. These observations illustrate
      that decreased diffusion can be present weeks after injury onset, and its
      presence cannot be used to time injury onset within 1 week, which could
      significantly impact determination of the proximate cause of fetal brain injury
      in future cases.

PMID- 20671063
TI  - Differences in microstructural alterations of the hippocampus in Alzheimer
      disease and idiopathic normal pressure hydrocephalus: a diffusion tensor imaging
      study.
AB  - BACKGROUND AND PURPOSE: DTI can be used to assess the degradation of WM tracts by
      measuring the FA and MD. Decreased FA/increased MD values in the AD hippocampus
      have been reported by many studies. In contrast, only a few studies reported on
      hydrocephalus by using the DTI technique. In elderly patients with dementia and
      with dilated ventricles, it is often difficult to differentiate iNPH from AD with
      visual measurements on MR imaging. The aim of this study was to investigate the
      changes of microstructural integrity of the hippocampus in iNPH by using DTI and
      determining whether this method could be a new diagnostic tool to differentiate
      iNPH from AD. MATERIALS AND METHODS: We recruited 43 participants (15 healthy
      controls, 15 patients with AD, and 13 patients with iNPH). The FA and MD values
      were measured by using the region-of-interest method in the hippocampal head,
      body, and tail on both sides. Clinical history, neurologic examination, and
      neuropsychological assessment were included. RESULTS: The FA values were the
      lowest in the patients with AD, the patients with iNPH, and the healthy controls
      in this order. The MD values were the highest in the same order. These findings
      were consistent in the 3 subdivisions of the bilateral hippocampal regions.
      Hippocampal volume was not different between patients with iNPH and AD.
      CONCLUSIONS: The microstructural alterations of the hippocampus were more
      sensitive than the volumetric changes in AD and iNPH. DTI analysis might be a
      useful tool for discriminating AD from iNPH.

PMID- 20671064
TI  - The serine protease HtrA1 specifically interacts and degrades the tuberous
      sclerosis complex 2 protein.
AB  - Hamartin and tuberin are products of the tumor suppressor genes TSC1 and TSC2,
      respectively. Mutations affecting either gene result in the tuberous sclerosis
      syndrome, a neurologic genetic disorder characterized by the formation of
      multiple benign tumors or hamartomas. In this study, we report the identification
      of TSC2, but not TSC1, as a substrate of HtrA1, a member of the human HtrA family
      proteins of serine proteases. We show the direct interaction and colocalization
      in the cytoplasm of HtrA1 and TSC2 and that HtrA1 cleaves TSC2 both in vitro and
      in vivo. Finally, we show that alterations in HtrA1 expression cause
      modifications in phosphorylation status of two downstream targets of TSC2: 4E-BP1
      and S6K. Our data suggest that, under particular physiologic or pathologic
      conditions, HtrA1 degrades TSC2 and activates the downstream targets. Considering
      that HtrA1 levels are significantly increased during embryogenesis, we speculate
      that one of the targets of HtrA1 activity during fetal development is the TSC2
      TSC1 pathway.

PMID- 20671065
TI  - High-density lipoprotein induces proliferation and migration of human prostate
      androgen-independent cancer cells by an ABCA1-dependent mechanism.
AB  - Androgen deprivation therapy for prostate cancer leads to a significant increase
      of high-density lipoprotein (HDL), which is generally viewed as beneficial,
      particularly for cardiovascular disease, but the effect of HDL on prostate cancer
      is unknown. In this study, we investigated the effect of HDL on prostate cancer
      cell proliferation, migration, intracellular cholesterol levels, and the role of
      cholesterol transporters, namely ABCA1, ABCG1, and SR-BI in these processes. HDL
      induced cell proliferation and migration of the androgen-independent PC-3 and
      DU145 cells by a mechanism involving extracellular signal-regulated kinase (ERK)
      1/2 and Akt, but had no effect on the androgen-dependent LNCaP cell, which did
      not express ABCA1 unlike the other cell lines. Treatment with HDL did not
      significantly alter the cholesterol content of the cell lines. Knockdown of ABCA1
      but not ABCG1 or SR-BI by small interfering RNA (siRNA) inhibited HDL-induced
      cell proliferation, migration, and ERK1/2 and Akt signal transduction in PC-3
      cells. Moreover, after treatment of LNCaP cells with charcoal-stripped fetal
      bovine serum, ABCA1 was induced ~10-fold, enabling HDL to induce ERK1/2
      activation, whereas small interfering RNA knockdown of ABCA1 inhibited HDL
      induced ERK1/2 activation. Simvastatin, which inhibited ABCA1 expression in PC-3
      and DU145 cells, attenuated HDL-induced PC-3 and DU145 cell proliferation,
      migration, and ERK1/2 and Akt phosphorylation. In human prostate biopsy samples,
      ABCA1 mRNA expression was ~2-fold higher in the androgen deprivation therapy
      group than in subjects with benign prostatic hyperplasia or pretreatment prostate
      cancer groups. In summary, these results suggest that HDL by an ABCA1-dependent
      mechanism can mediate signal transduction, leading to increased proliferation and
      migration of prostate cancer cells.

PMID- 20671066
TI  - Xrcc2 modulates spontaneous and radiation-induced tumorigenesis in Apcmin/+ mice.
AB  - XRCC2 has an important role in repair of DNA damage by homologous recombination.
      Adult Apc(min/+) (min, multiple intestinal neoplasia) mice, wild-type or
      heterozygous for Xrcc2 deficiency, were sham-irradiated or 2-Gy X-irradiated.
      Spontaneous mammary and intestinal tumor incidences are lower in Apc(min/+)
      Xrcc2(+/-) mice than in Apc(min/+) Xrcc2(+/+) mice (mammary tumors: 14% and 38%,
      respectively, chi(2) P = 0.03; intestinal adenomas in mice reaching full life
      span: 108.6 and 130.1, respectively, t-test P = 0.005). Following irradiation,
      the increase in mammary tumors was greatest in female mice heterozygous for Xrcc2
      (7.25 +/- 0.50-fold in Apc(min/+) Xrcc2(+/-) mice compared with 2.57 +/- 0.35
      fold in Apc(min/+) Xrcc2(+/+) mice; t-test P < 0.001). The increase in intestinal
      tumor multiplicity following irradiation was significantly greater in Apc(min/+)
      Xrcc2(+/-) mice (Apc(min/+) Xrcc2(+/-), 4.14 +/- 0.05-fold, versus Apc(min/+)
      Xrcc2(+/+), 3.30 +/- 0.05-fold; t-test P < 0.001). Loss of heterozygosity of all
      chromosome 18 markers was greater in intestinal tumors from Apc(min/+) Xrcc2(+/-)
      mice than in tumors from Apc(min/+) Xrcc2(+/+) mice. These findings indicate that
      Xrcc2 haploinsufficiency reduces spontaneous tumor incidence on an Apc(min/+)
      background but increases the tumorigenic response to radiation.

PMID- 20671067
TI  - An optical method to quantify the density of ligands for cell adhesion receptors
      in three-dimensional matrices.
AB  - The three-dimensional matrix that surrounds cells is an important insoluble
      regulator of cell phenotypes. Examples of such insoluble surfaces are the
      extracellular matrix (ECM), ECM analogues and synthetic polymeric biomaterials.
      Cell-matrix interactions are mediated by cell adhesion receptors that bind to
      chemical entities (adhesion ligands) on the surface of the matrix. There are
      currently no established methods to obtain quantitative estimates of the density
      of adhesion ligands recognized by specific cell adhesion receptors. This article
      presents a new optical-based methodology for measuring ligands of adhesion
      receptors on three-dimensional matrices. The study also provides preliminary
      quantitative results for the density of adhesion ligands of integrins
      alpha(1)beta(1) and alpha(2)beta(1) on the surface of collagen-based scaffolds,
      similar to biomaterials that are used clinically to induce regeneration in
      injured skin and peripheral nerves. Preliminary estimates of the surface density
      of the ligands of these two major collagen-binding receptors are 5775 +/- 2064
      ligands microm(-2) for ligands of alpha(1)beta(1) and 17 084 +/- 5353 ligands
      microm(-2) for ligands of alpha(2)beta(1). The proposed methodology can be used
      to quantify the surface chemistry of insoluble surfaces that possess biological
      activity, such as native tissue ECM and biomaterials, and therefore can be used
      in cell biology, biomaterials science and regenerative medical studies for
      quantitative description of a matrix and its effects on cells.

PMID- 20671068
TI  - A strain-cue hypothesis for biological network formation.
AB  - The direction of migration of a cell invading a host population is assumed to be
      controlled by the magnitude of the strains in the host medium (cells plus
      extracellular matrix) that arise as the host medium deforms to accommodate the
      invader. The single assumption that invaders are cued by strains external to
      themselves is sufficient to generate network structures. The strain induced by a
      line of invaders is greatest at the extremity of the line and thus the strain
      field breaks symmetry, stabilizing branch formation. The strain cue also triggers
      sprouting from existing branches, with no further model assumption. Network
      characteristics depend primarily on the ratio of the rate of advance of the
      invaders to the rate of relaxation of the host cells after their initial
      deformation. Intra-cell mechanisms that govern these two rates control network
      morphology. The strain field that cues an individual invader is a collective
      response of the combined cell populations, involving the nearest 100 cells, to
      order of magnitude, to any invader. The mechanism does not rely on the pre
      existence of the entire host medium prior to invasion; the host cells need only
      maintain a layer several cells thick around each invader. Consistent with recent
      experiments, networks result only from a strain cue that is based on strain
      magnitudes. Spatial strain gradients do not break symmetry and therefore cannot
      stabilize branch formation. The theory recreates most of the geometrical features
      of the nervous network in the mouse gut when the most influential adjustable
      parameter takes a value consistent with one inferred from human and mouse
      amelogenesis. Because of similarity in the guiding local strain fields, strain
      cues could also be a participating factor in the formation of vascular networks.

PMID- 20671069
TI  - Analysis of the soft tissue profile in Croatians with normal occlusions and well
      balanced faces.
AB  - The aim of the study was to test the hypothesis that there is no difference
      between the soft tissue profile of Croatian and white North American adults.
      Facial profile photographs were taken of 110 Croatians (52 males and 58 females)
      with normal occlusions and well-balanced faces (age 22-29 years). The findings
      were also compared with a white Brazilian group. An independent Student's t-test
      (P < 0.05) was used to compare the soft tissue parameters of Croatians with those
      of North Americans and to assess gender differences. The soft tissue profile
      measurements that showed significant gender dimorphism (P < 0.001) were the true
      vertical line [(TVL)-nasal tip (NT)] and TVL-point B, indicating that the males
      had slightly greater nasal prominence (mean difference: 1.32 mm) and deeper
      labial sulci (mean difference: 2.04 mm) compared with the females. The upper lip
      was the same for both genders (1.25 mm), while the lower lip was 0.97 mm more
      prominent in females than in males. All soft tissue variables, except TVL-NT
      showed significant differences between Croatian and white American female
      subjects (P = 0.096). For male subjects, nasolabial angle was the only variable
      that showed no statistically significant difference between the two populations.
      A universal standard of facial aesthetic is not applicable to diverse white
      populations. These differences should be considered in diagnosis and treatment
      planning for Croatians, together with their individual characteristics.

PMID- 20671070
TI  - Longitudinal changes in microbiology and clinical periodontal parameters after
      removal of fixed orthodontic appliances.
AB  - The aim of this longitudinal study was to monitor patients' microbiological and
      clinical parameters from bracket placement up to 3 months post-treatment. Twenty
      four patients (10 males and 14 females, aged 14.6 +/- 1.0 years) were included in
      this investigation. Microbiology (sub- and supragingival), periodontal probing
      depth (PPD), bleeding on probing (BOP), and gingival crevicular fluid (GCF) flow
      were assessed at baseline (T1), at bracket removal (T2), and 3 months post
      treatment (T3). A statistical comparison was made over time and between the
      banded, bonded, and control sites. Repeated measurements on patients were taken
      into account by modelling the patients as a random factor. Except for PPD and
      BOP, values were log-transformed before analysis. Corrections for simultaneous
      hypothesis testing were performed via simulation. The results demonstrated that
      sub- and supragingival colony-forming units ratio (CFU ratio aerobe/anaerobe)
      decreased significantly (relatively more anaerobes) at T2 compared with T1.
      Between T2 and T3 no significant increase in CFU ratio was seen, resulting in a
      significantly lower CFU ratio at T3 compared with T1 for subgingival plaque. The
      difference concerning supragingival plaque between T3 and T1 was not significant.
      Clinical parameters PPD, POB, and GCF flow showed a significant increase between
      T1 and T2. Between T2 and T3 these variables decreased significantly but remained
      significantly higher than at T1 [except for BOP values at the bonded sites (P =
      0.0646)]. Placement of fixed orthodontic appliances has an influence both on
      microbial and clinical periodontal parameters, which were only partly normalized,
      3 months following the removal of the appliances.

PMID- 20671071
TI  - Obesity up-regulates intermediate conductance calcium-activated potassium
      channels and myoendothelial gap junctions to maintain endothelial vasodilator
      function.
AB  - The mechanisms involved in altered endothelial function in obesity-related
      cardiovascular disease are poorly understood. This study investigates the effect
      of chronic obesity on endothelium-dependent vasodilation and the relative
      contribution of nitric oxide (NO), calcium-activated potassium channels (K(Ca)),
      and myoendothelial gap junctions (MEGJs) in the rat saphenous artery. Obesity was
      induced by feeding rats a cafeteria-style diet (~30 kJ as fat) for 16 to 20
      weeks, with this model reflecting human dietary obesity etiology. Age- and sex
      matched controls received standard chow (~12 kJ as fat). Endothelium-dependent
      vasodilation was characterized in saphenous arteries by using pressure myography
      with pharmacological intervention, Western blotting, immunohistochemistry, and
      ultrastructural techniques. In saphenous artery from control, acetylcholine (ACh)
      mediated endothelium-dependent vasodilation was blocked by NO synthase and
      soluble guanylate cyclase inhibition, whereas in obese rats, the ACh response was
      less sensitive to such inhibition. Conversely, the intermediate conductance K(Ca)
      (IK(Ca)) blocker 1-[(2-chlorophenyl)diphenyl-methyl]-1H pyrazole attenuates ACh
      mediated dilation in obese, but not control, vessels. In a similar manner,
      putative gap junction block with carbenoxolone increased the pEC(50) for ACh in
      arteries from obese, but not control, rats. IK1 protein and MEGJ expression was
      up-regulated in the arteries of obese rats, an observation absent in control.
      Addition of the small conductance K(Ca) blocker apamin had no effect on ACh
      mediated dilation in either control or obese rat vessels, consistent with
      unaltered SK3 expression. Up-regulation of distinct IK(Ca)- and gap junction
      mediated pathways at myoendothelial microdomain sites, key mechanisms for
      endothelial-derived hyperpolarization-type activity, maintains endothelium
      dependent vasodilation in diet-induced obese rat saphenous artery. Plasticity of
      myoendothelial coupling mechanisms represents a significant potential target for
      therapeutic intervention.

PMID- 20671072
TI  - Peroxisome proliferator-activated receptor {alpha} agonism prevents renal damage
      and the oxidative stress and inflammatory processes affecting the brains of
      stroke-prone rats.
AB  - A growing body of evidence suggests that chronic kidney disease is a significant
      risk for cardiovascular events and stroke regardless of traditional risk factors.
      The aim of this study was to examine the effects of peroxisome proliferator
      activated receptor (PPAR) agonists on the tissue damage affecting salt-loaded
      spontaneously hypertensive stroke-prone rats ( SHRSPs), an animal model that
      develops a complex pathology characterized by systemic inflammation,
      hypertension, and proteinuria and leads to end-organ injury (initially renal and
      subsequently cerebral). Compared with the PPARgamma agonist rosiglitazone, the
      PPARalpha ligands fenofibrate and clofibrate significantly increased survival (p
      < 0.001) by delaying the occurrence of brain lesions monitored by magnetic
      resonance imaging (p < 0.001) and delaying increased proteinuria (p < 0.001).
      Fenofibrate completely prevented the renal disorder characterized by severe
      vascular lesions, tubular damage, and glomerular sclerosis, reduced the number of
      ED-1-positive cells and collagen accumulation, and decreased the renal expression
      of interleukin-1beta, transforming growth factor beta, and monocyte
      chemoattractant protein 1. It also prevented the plasma and urine accumulation of
      acute-phase and oxidized proteins, suggesting that the protection induced by
      PPARalpha agonists was at least partially caused by their anti-inflammatory and
      antioxidative properties. The results of this study demonstrate that PPAR agonism
      has beneficial effects on spontaneous brain and renal damage in SHRSPs by
      inhibiting systemic inflammation and oxidative stress, and they support carrying
      out future studies aimed at evaluating the effect of PPARalpha agonists on
      proteinuria and clinical outcomes in hypertensive patients with renal disease at
      increased risk of stroke.

PMID- 20671073
TI  - System-wide learning from root cause analysis: a report from the New South Wales
      Root Cause Analysis Review Committee.
AB  - BACKGROUND: Preventable errors are common in healthcare. Over the last decade,
      Root Cause Analysis (RCA) has become a key tool for healthcare services to
      investigate adverse events and try to prevent them from happening again. The
      purpose of this paper is to highlight the work of the New South Wales (NSW) RCA
      Review Committee. The benefits of correctly classifying, aggregating and
      disseminating RCA data to clinicians will be discussed. In NSW, we perform an
      average of 500 RCAs per year. It is estimated that each RCA takes between 20 and
      90 h to perform. In 2007, the NSW Clinical Excellence Commission (CEC) and the
      Quality and Safety Branch at the Department of Health constituted an RCA review
      committee. 445 RCAs were reviewed by the committee in 14 months. 41 RCAs were
      related to errors in managing acute coronary syndrome. RESULTS AND DISCUSSION:
      The large number of RCAs has enabled the committee to identify emerging themes
      and to aggregate the information about underlying human (staff), patient and
      system factors. The committee has developed a taxonomy based on previous work
      done within health and aviation and assesses each RCA against this set of
      criteria. The effectiveness of recommendations made by RCA teams requires further
      review. There has been conjecture that staff do not feel empowered to articulate
      root causes which are beyond the capacity of the local service to address.
      CONCLUSION: Given the number of hours per RCA, it seems a shame that the final
      output of the process may not in fact achieve the desired patient safety
      improvements.

PMID- 20671074
TI  - Introduction of a comprehensive management protocol for severe sepsis is
      associated with sustained improvements in timeliness of care and survival.
AB  - INTRODUCTION: Mortality from severe sepsis can be improved by timely diagnosis
      and treatment. This study investigates the effectiveness of a comprehensive
      management protocol for recognition and initial treatment of severe sepsis that
      spans from the emergency department (ED) to the intensive care unit. METHODS:
      Interventions included development of a management algorithm including early goal
      directed therapy, a computerised physician order entry set for suspected sepsis,
      introduction of invasive haemodynamic monitoring and antibiotics stocked in the
      ED, and an extensive education campaign involving ED nurses and physicians. MAIN
      RESULTS: In the 6 months after introduction of the protocol, 37 patients who had
      severe sepsis were identified in the ED. Compared to a randomly selected group of
      37 patients who had severe sepsis and who were transferred directly to the
      intensive care unit before introduction of the protocol, significant improvements
      were observed in mean time to initiation of early goal-directed therapy (3.2 vs
      10.4h, p=0.001) and to achievement of resuscitation goals (10.4 vs 30.1h,
      p=0.007). There was a trend towards more rapid administration of antibiotics (1.4
      vs 2.7h, p=0.06). This was associated with a decrease in crude hospital mortality
      rate from 51.4% to 27.0% (absolute risk reduction=24%, 95% CI 3% to 47%).
      Improvements were sustained in the follow-up audit at 16 months. CONCLUSIONS:
      Introduction of a comprehensive management protocol to address early recognition
      and management of severe sepsis in the ED is associated with sustained
      improvements in processes of care.

PMID- 20671075
TI  - A multi-faceted approach to the physiologically unstable patient.
AB  - BACKGROUND: Patients on general hospital wards who deteriorate clinically are
      often not recognised as needing an escalation in care, and effective
      interventions are delayed. This study reviews a multifaceted approach to the
      identification and management of these patients in a large metropolitan hospital
      in Auckland, New Zealand. STRATEGIES FOR CHANGE: Four interventions were combined
      into the Physiologically Unstable Patient (PUP) programme. These were: (1)
      redesign of the vital sign observation chart; (2) introduction of an early
      warning scoring system; (3) deployment of a nurse-led rapid response team; and
      (4) a comprehensive ward-based education programme. KEY MEASURES FOR IMPROVEMENT:
      Completeness and accuracy of routine observations; actions taken in accordance
      with the algorithm; impact on medical emergency team callouts, cardiac arrest
      calls and unplanned intensive care unit admissions. EFFECTS OF CHANGE: The PUP
      programme was implemented in 16 wards over 15 months. Vital sign recording
      improved, and the PUP score became a recognised metric for prioritising patients
      for review. Consistent with others' experience, there was a reluctance to call
      for help. Raised PUP scores prompted action around 30% of the time on average.
      Medical emergency team calls increased significantly from a median of 27.5 calls
      per month to 70.5. There was no significant change in unplanned transfers to
      intensive care unit or in cardiac arrest calls. LESSONS LEARNT: A multifaceted
      programme to identify physiologically unstable patients on general wards can be
      introduced and can improve the recognition of such patients, but there are still
      barriers to ensuring that these patients receive the extra care that they
      require. These systemic failings need to be investigated and addressed for real
      change to occur.

PMID- 20671076
TI  - Safety through redundancy: a case study of in-hospital patient transfers.
AB  - OBJECTIVES: To study the extent and execution of redundant processes during
      inpatient transfers to Radiology, and their impact on errors during the transfer
      process; to explore the use of causal and reliability analyses for modelling
      error detection and redundancy in the transfer process; and to provide guidance
      on potential system improvements. METHODS: A prospective observational study at a
      metropolitan teaching hospital. 101 patient transfers to Radiology were observed
      over a 6-month period, and errors in patient transfer process were recorded.
      Fault Tree Analysis was used to model error paths and identify redundant steps.
      Reliability Analysis was used to quantify system reliability. RESULTS: 420 errors
      were noted, an average of four errors per transfer. No incidents of patient harm
      were recorded. Inadequate handover was the most common error (43.1%), followed by
      failure to perform patient identification checks (41.9%), patient inadequately
      prepared for transfer (7.4%), inadequate infection control precautions (2.9%),
      inadequate clinical escort (2.1%), inadequate transport vehicle (2.1%) and
      equipment failure (0.2%). Four redundant steps for communicating patients'
      infectious status were identified (reliability=0.07, 0.37, 0.26, 0.31).
      Collectively, these yielded a system reliability of 0.7. The low reliability of
      each individual step was due to its low rate of execution. CONCLUSIONS: Analysis
      of the transfer process revealed a number of redundancies that safeguard against
      transfer errors. However, they were relatively ineffective in preventing errors,
      due to the poor compliance rate. Thus, the authors advocate increasing compliance
      to existing redundant processes as an improvement strategy, before investing
      resources on new processes.

PMID- 20671077
TI  - Improving management of oesophageal varices in patients with cirrhosis.
AB  - PROBLEM: A retrospective audit of management of oesophageal varices in patients
      with cirrhosis identified the need to improve adherence to guidelines. DESIGN:
      Prospective audit of the effect of disseminating guidelines in 2004; prospective
      audit of the effect of a nurse coordinator for oesophageal variceal screening and
      surveillance from 2005 to 2008. SETTING: A major public hospital in Australia
      2001-2008. Patients with cirrhosis of the liver and those who had experienced a
      variceal bleed were studied. KEY MEASURES FOR IMPROVEMENT: (1) Adherence with
      primary prevention protocols for prevention of primary variceal bleeding in
      patients with cirrhosis of the liver. (2) Adherence with protocols for acute
      management of variceal bleeding and secondary prevention of bleeding. STRATEGIES
      FOR CHANGE: Local protocols were developed and disseminated. A nurse coordinator
      was introduced to manage the primary prevention process according to a clinical
      protocol. EFFECTS OF CHANGE: The introduction of a nurse coordinator to manage
      the primary prevention process resulted in dramatic and rapid improvements in
      primary prevention. This has been maintained with our target of 90% adherence
      being achieved for the last 3 years. LESSONS LEARNT: Disseminating guidelines had
      little effect on primary prevention practice. Less than 1 year after a nurse
      coordinator was introduced to manage primary prevention, adherence to primary
      prevention guidelines increased from 13% to 79%. However, significant
      improvements in the management of acute variceal bleeding where medical staff
      have a clear responsibility for patient care were achieved through the
      development and dissemination of clear clinical protocols and the introduction of
      auditing and feedback mechanisms.

PMID- 20671078
TI  - Pressure ulcers and incontinence-associated dermatitis: effectiveness of the
      Pressure Ulcer Classification education tool on classification by nurses.
AB  - CONTEXT: Previous studies report that pressure ulcer classification and
      differentiation from incontinence associated dermatitis are difficult. Incorrect
      classification and differentiation result in incorrect prevention and treatment.
      Education is important to spread evidence-based insights about this topic and to
      improve classification skills. AIM: To assess the effectiveness of the Pressure
      Ulcer Classification (PUCLAS) education tool. PUCLAS was developed by the PUCLAS
      Workgroup of the European Pressure Ulcer Advisory Panel. DESIGN: Randomised
      controlled trial. SETTING AND PARTICIPANTS: A convenience sample of 1217 Belgian,
      Dutch, British and Portuguese nurses. OUTCOME MEASURE: Correct classification of
      pressure ulcer photographs and differentiation from photographs of incontinence
      associated dermatitis. RESULTS: Baseline, 44.5% of the photographs were
      classified correctly. In the post-test, the results in the intervention group
      were significantly higher (63.2%) compared with the control group (53.1%;
      p<0.001). The percentage of correct assessments of incontinence associated
      dermatitis (IAD) was 70.7% in the intervention group and 35.6% in the control
      group (p<0.001). The skill to differentiate IAD from pressure ulcers was
      significantly associated with the experimental intervention (OR 4.07, 95% CI 3.21
      to 5.15, p<0.001). CONCLUSION: The PUCLAS tool improved pressure ulcer
      classification and IAD differentiation significantly.

PMID- 20671079
TI  - Incidence of medication errors and adverse drug events in the ICU: a systematic
      review.
AB  - BACKGROUND: Medication errors (MEs) and adverse drug events (ADEs) are both
      common and under-reported in the intensive care setting. The definitions of these
      terms vary substantially in the literature. Many methods have been used to
      estimate their incidence. METHODS: A systematic review was done to assess methods
      used for tracking unintended drug events in intensive care units (ICUs). Studies
      published up to 22 June 2007 were identified by searching eight online databases,
      including Medline. In total, 613 studies were evaluated for inclusion by two
      reviewers. RESULTS: The authors selected 29 papers to analyse; all studies took
      place in an ICU, were reproducible and reported ICU-specific rates of events.
      Rates of MEs varied from 8.1 to 2344 per 1000 patient-days, and ADEs from 5.1 to
      87.5 per 1000 patient-days. The definitions of ADE and ME in the studies varied
      widely. CONCLUSIONS: Much variation exists in reported rates and definitions of
      ADEs and MEs in ICUs. Some of this variation may be due to a lack of standard
      definitions for ADEs and MEs, and methods for detecting them. Further
      standardisation is needed before these methods can be used to evaluate process
      improvements.

PMID- 20671080
TI  - Optimal search filters for detecting quality improvement studies in Medline.
AB  - BACKGROUND: As the knowledge translation and comparative effectiveness research
      agendas gain momentum, we can expect more evidence on which to base quality
      improvement (QI) programmes. Unaided searches for such content in the literature,
      however, are likely to be daunting, with searches missing key articles while
      mainly retrieving articles that are irrelevant to the question being asked. The
      objective of this study was to develop and validate optimal Medline search
      filters for retrieving original and review articles about clinical QI. METHODS:
      Analytical survey in the McMaster Clinical Hedges database and Health Knowledge
      Refinery (HKR) of 161 clinical journals to determine the operating
      characteristics of QI search filters developed by computerised combinations of
      terms selected to detect original QI studies and systematic reviews meeting basic
      methodological criteria for scientific merit. Results from a derivation random
      subset of articles were tested in a validation random subset. RESULTS: The
      Clinical Hedges QI database contained 49,233 citations of which 471 (0.96%) were
      original or review QI studies; of those, 282 (60%) were methodologically sound.
      Combinations of search terms reached peak sensitivities of 100% at a specificity
      of 89.3% for detecting methodologically sound original and review QI studies, and
      sensitivities of 97.6% at a specificity of 53.0% for detecting all original and
      review QI studies independent of rigour. Operating characteristics of the search
      filters derived in the development database worked similarly in the validation
      database, without statistical differences. CONCLUSION: New empirically derived
      Medline search filters have been validated to optimise retrieval of original and
      review QI articles.

PMID- 20671081
TI  - Automated detection of harm in healthcare with information technology: a
      systematic review.
AB  - CONTEXT: To improve patient safety, healthcare facilities are focussing on
      reducing patient harm. Automated harm-detection methods using information
      technology show promise for efficiently measuring harm. However, there have been
      few systematic reviews of their effectiveness. OBJECTIVE: To perform a systematic
      literature review to identify, describe and evaluate effectiveness of automated
      inpatient harm-detection methods. METHODS: Data sources included MEDLINE and
      CINAHL databases indexed through August 2008, extended by bibliographic review
      and search of citing articles. The authors included articles reporting
      effectiveness of automated inpatient harm-detection methods, as compared with
      other detection methods. Two independent reviewers used a standardised
      abstraction sheet to extract data about automated and comparison harm-detection
      methods, patient samples and events identified. Differences were resolved by
      discussion. RESULTS: From 176 articles, 43 articles met inclusion criteria: 39
      describing field-defined methods, two using natural language processing and two
      using both methods. Twenty-one studies used automated methods to detect adverse
      drug events, 10 detected general adverse events, eight detected nosocomial
      infections, and four detected other specific adverse events. Compared with gold
      standard chart review, sensitivity and specificity of automated harm-detection
      methods ranged from 0.10 to 0.94 and 0.23 to 0.98, respectively. Studies used
      heterogeneous methods that often were flawed. CONCLUSION: Automated methods of
      harm detection are feasible and some can potentially detect patient harm
      efficiently. However, effectiveness varied widely, and most studies had
      methodological weaknesses. More work is needed to develop and assess these tools
      before they can yield accurate estimates of harm that can be reliably interpreted
      and compared.

PMID- 20671082
TI  - The Turkish version of the safety attitudes questionnaire: psychometric
      properties and baseline data.
AB  - OBJECTIVE: To test the psychometric soundness of the Safety Attitudes
      Questionnaire (SAQ) in Turkish hospitals, examine differences in perceptions of
      safety and provide baseline data. METHODS: The SAQ (inpatient version) was
      translated with the back-translation technique into Turkish. Ten out of 50
      teaching hospitals belonging to the Ministry of Health in Turkey were selected
      randomly. The Turkish version of the SAQ was administered to a sample of 2000
      care givers at 10 hospitals. The factor structure of the responses was tested by
      confirmatory factor analysis. Cronbach alphas were calculated, and the mean and
      percentage positive safety attitude scores were assessed. RESULTS: The response
      rate was 67.5%. Cronbach alphas of six factors (teamwork climate, safety climate,
      job satisfaction, stress recognition, perceptions of management, and working
      conditions) ranged from 0.66 to 0.77. Goodness-of-fit indices from the
      confirmatory factor analysis showed a reasonable model fit. There was a
      substantial variability among hospitals in terms of items and factors. Baseline
      data for the Turkish hospitals are presented. CONCLUSION: The Turkish translation
      of the SAQ showed satisfactory internal psychometric properties. Attitudes
      relevant to safety culture vary widely by hospital and indicate a need for
      improvement. Survey findings provide a baseline for future benchmarking.

PMID- 20671083
TI  - Are Australian smokers interested in using low-nitrosamine smokeless tobacco for
      harm reduction?
AB  - AIMS: To determine (1) whether Australian smokers are aware of low-nitrosamine
      smokeless tobacco (LNSLT) products and (2) whether they would be interested in
      using LNSLT either as a long-term substitute for smoking or as an aid to
      quitting, if these products were to become legally available. METHODS: 401 daily
      smokers were recruited by a market research company to complete an internet
      questionnaire about their smoking history, knowledge of smokeless tobacco and
      intentions to purchase LNSLT under different scenarios. FINDINGS: Just under half
      (48%) indicated they were willing to buy an LNSLT product. Predictors of an
      interest in purchasing LNSLT were low income, poorer health, prior SLT use,
      belief that SLT is less harmful than cigarettes, switching to a lower tar
      cigarette in the past year, ever using nicotine replacement therapy products for
      quitting or other reasons, having made a failed cessation attempt in the previous
      year and not planning to quit smoking. Analysis of quitting and LNSLT purchasing
      intentions under different scenarios suggest that making LNSLT available at a
      much lower cost than smoked cigarettes while increasing taxes on cigarettes could
      provide a greater reduction in the number of smokers than the same tax increase
      alone. These results support further examination of the potential for LNSLT to
      reduce smoking-related harm in Australia.

PMID- 20671084
TI  - Resequencing microarray for detection of human adenoviruses in patients with
      community-acquired gastroenteritis: a proof-of-concept study.

PMID- 20671085
TI  - Rapid diagnosis of typhoid fever by an in-house flagellin PCR.

PMID- 20671086
TI  - High degree of genetic diversity of non-polio enteroviruses identified in Georgia
      by environmental and clinical surveillance, 2002-2005.
AB  - Enterovirus surveillance data are useful for establishing temporal and
      geographical patterns of circulation and for virus characterization to determine
      phylogenetic relationships between strains. Almost no information is available on
      circulating enteroviruses in Georgia and the surrounding region. To describe
      enterovirus circulation in Georgia, determine relationships with previously
      characterized strains and assess the role of environmental and clinical
      enterovirus surveillance, this study analysed a total of 112 non-polio
      enterovirus isolates identified during 2002-2005 from sewage and human stool
      samples. Viruses were isolated in cell culture using standard methods and typed
      by partial sequencing of the VP1 gene. A total of 20 different non-polio
      enterovirus serotypes were identified over the 4-year period. The most commonly
      detected enteroviruses included echovirus (E) 6 (21 isolates; 18.8 %), E20, E3
      and E7 (11 isolates each; 9.8 %), E11, coxsackievirus (CV) B4 and CVB5 (seven
      isolates each; 6.3 %), and E13, E19 and E30 (six isolates each; 5.4 %).
      Phylogenetic analysis showed that many serotypes were represented by more than
      one genetic lineage. The present study showed a very high degree of enterovirus
      diversity in Georgia and demonstrated the added value of environmental
      enterovirus surveillance, particularly in settings with limited clinical
      surveillance. Several serotypes would not have been detected without having both
      clinical and environmental surveillance in place. Several serotypes detected in
      Georgia were among those rarely reported in the USA and Europe (e.g. E3, E20 and
      E19). As the emergence of new genetic lineages of enterovirus in a particular
      area is often associated with large-scale outbreaks, continued monitoring of
      enterovirus strains by both environmental and clinical surveillance and genetic
      characterization should be encouraged.

PMID- 20671087
TI  - Commensal Escherichia coli of healthy humans: a reservoir for antibiotic
      resistance determinants.
AB  - This study examined in detail the population structure of Escherichia coli from
      healthy adults with respect to the prevalence of antibiotic resistance and
      specific resistance determinants. E. coli isolated from the faeces of 20 healthy
      adults not recently exposed to antibiotics was tested for resistance to ten
      antibiotics and for carriage of integrons and resistance determinants using PCR.
      Strain diversity was assessed using biochemical and molecular criteria. E. coli
      was present in 19 subjects at levels ranging from 2.0*10(4) to 1.7*10(8) c.f.u.
      (g faeces)(-1). Strains resistant to one to six antibiotics were found at high
      levels (>30 %) in only ten individuals, but at significant levels (>0.5 %) in 14.
      Resistant isolates with the same phenotype from the same individual were
      indistinguishable, but more than one susceptible strain was sometimes found.
      Overall, individuals harboured one to four E. coli strains, although in 17
      samples one strain was dominant (>70 % of isolates). Eighteen strains resistant
      to ampicillin, sulfamethoxazole, tetracycline and trimethoprim in 15 different
      combinations were observed. One resistant strain was carried by two unrelated
      individuals and a susceptible strain was shared by two cohabiting subjects. Two
      minority strains were derivatives of a more abundant resistant strain in the same
      sample, showing that continuous evolution is occurring in vivo. The trimethoprim
      resistance genes dfrA1, dfrA5, dfrA7, dfrA12 or dfrA17 were in cassettes in a
      class 1 or class 2 integron. Ampicillin resistance was conferred by the bla(TEM)
      gene, sulfamethoxazole resistance by sul1, sul2 or sul3 and tetracycline
      resistance by tetA(A) or tetA(B). Chloramphenicol resistance (cmlA1 gene) was
      detected only once. Phylogenetic groups A and B2 were more common than B1 and D.
      Commensal E. coli of healthy humans represent an important reservoir for numerous
      antibiotic-resistance genes in many combinations. However, measuring the true
      extent of resistance carriage in commensal E. coli requires in-depth analysis.

PMID- 20671088
TI  - Usefulness of the hsp60 gene for the identification and classification of Gram
      negative anaerobic rods.
AB  - The hsp60 gene sequences were determined for 121 strains of Gram-negative
      anaerobic rods, including the genera Bacteroides, Barnesiella, Butyricimonas,
      Odoribacter, Parabacteroides, Paraprevotella, Porphyromonas, Prevotella and
      Tannerella. The mean pairwise hsp60 gene sequence similarity (73.8-97.1 %)
      between species in each genus, except for the genus Tannerella that comprises one
      species, was significantly less than that of the 16S rRNA gene sequence (88.3
      96.3 %). Only pairwise hsp60 gene sequence similarity (97.1 %) of the genus
      Paraprevotella was higher than that of the 16S rRNA gene sequence (93.8 %). Each
      genus formed a distinct clade in the phylogenetic analysis of the hsp60 gene
      sequence as well as the 16S rRNA gene sequence. The phylogenetic analysis
      indicated a higher evolutionary rate for the hsp60 gene sequence than the 16S
      rRNA gene sequence, especially in the genera Porphyromonas and Prevotella. This
      study suggests that the hsp60 gene is a useful alternative phylogenetic marker
      for the identification and classification of a broad range of Gram-negative
      anaerobic rods.

PMID- 20671089
TI  - Word wars and tobacco control: saying what needs saying that we don't yet know
      how to say, or saying it better.
AB  - To help officially launch the Tobacco Control Blog, this month's Editorial has
      also been posted to the blog and is ready for your comments. The aim of this blog
      is to stimulate debate, generate ideas and explore new and, at times,
      controversial ideas. Increasing the opportunities for interaction between
      readers, authors, and editors is essential to ensuring that the journal remains
      on the leading edge in today's world of instant and constant digital
      communication. In keeping with this theme, editor Ruth Malone raises the issue of
      how important language is in defining and framing the tobacco pandemic and
      challenges readers to share their own creative ideas for "language weapons." To
      entice you to join the conversation and make a suggestion, the best idea will win
      a one-year online subscription to Tobacco Control. The TC blog can be found here:
      http://blogs.bmj.com/tc/ We look forward to meeting you there. Tobacco Control
      Editorial Team.

PMID- 20671090
TI  - Indonesia: World Cup deja vu.

PMID- 20671091
TI  - How do tobacco retail displays affect cessation attempts? Findings from a
      qualitative study.
AB  - BACKGROUND: Tobacco retail displays promote smoking experimentation among youth;
      however, little is known about their effect on smokers making a quit attempt.
      Calls to ban tobacco retail displays would be strengthened if this measure would
      deter initiation and support cessation. METHODS: Semistructured in-depth
      interviews were conducted with 20 individuals, from two New Zealand provincial
      cities, who had attempted to quit smoking in the last 6 months. RESULTS: Tobacco
      products had high visibility, and elicited emotional and physical reactions that
      created on-going temptation, complicated cessation attempts and stimulated
      impulse purchases. Participants strongly supported banning tobacco retail
      displays primarily because they thought this would reduce youth initiation,
      promote greater consistency with smoke-free promotions and assist those
      attempting to quit. CONCLUSIONS: The effects of tobacco retail displays on
      smokers making a cessation attempt are explored. The findings are consistent with
      experimental and survey research, and expand a growing evidence base that
      supports government-mandated bans on tobacco retail displays.

PMID- 20671092
TI  - The alchemy of Marlboro: transforming 'light' into 'gold' in Mexico.

PMID- 20671094
TI  - Overall diet history and reversibility of the metabolic syndrome over 5 years:
      the Whitehall II prospective cohort study.
AB  - OBJECTIVE: We examined the impact of adherence to the Alternative Healthy Eating
      Index (AHEI), a set of dietary guidelines targeting major chronic diseases, on
      metabolic syndrome (MetS) reversion in a middle-aged population. RESEARCH DESIGN
      AND METHODS: Analyses were carried out on the 339 participants (28% women, mean
      age 56.4 years) from the Whitehall II study with MetS as defined by the National
      Cholesterol Education Program Adult Treatment Panel III criteria. Reversion was
      defined as not having MetS after 5 years of follow-up (158 case subjects).
      RESULTS: After controlling for potential confounders, adherence to AHEI was
      associated with MetS reversion (odds ratio 1.88 [95% CI 1.04-3.41]),
      predominantly in participants with central obesity and in those with high
      triglyceride. CONCLUSIONS: Our findings support the benefit of adherence to AHEI
      dietary guidelines for individuals with MetS, especially those with central
      obesity or high triglyceride levels.

PMID- 20671095
TI  - Urine proteome analysis may allow noninvasive differential diagnosis of diabetic
      nephropathy.
AB  - OBJECTIVE: Chronic renal insufficiency and/or proteinuria in type 2 diabetes may
      stem from chronic renal diseases (CKD) other than classic diabetic nephropathy in
      more than one-third of patients. We interrogated urine proteomic profiles
      generated by surface-enhanced laser desorption/ionization-time of flight/mass
      spectrometry with the aim of isolating a set of biomarkers able to reliably
      identify biopsy-proven diabetic nephropathy and to establish a stringent
      correlation with the different patterns of renal injury. RESEARCH DESIGN AND
      METHODS: Ten micrograms of urine proteins from 190 subjects (20 healthy subjects,
      20 normoalbuminuric, and 18 microalbuminuric diabetic patients and 132 patients
      with biopsy-proven nephropathy: 65 diabetic nephropathy, 10 diabetic with
      nondiabetic CKD [nd-CKD], and 57 nondiabetic with CKD) were run using a CM10
      ProteinChip array and analyzed by supervised learning methods (Classification and
      Regression Tree analysis). RESULTS: The classification model correctly identified
      75% of patients with normoalbuminuria, 87.5% of those with microalbuminuria, and
      87.5% of those with diabetic nephropathy when applied to a blinded testing set.
      Most importantly, it was able to reliably differentiate diabetic nephropathy from
      nd-CKD in both diabetic and nondiabetic patients. Among the best predictors of
      the classification model, we identified and validated two proteins, ubiquitin and
      beta2-microglobulin. CONCLUSIONS: Our data suggest the presence of a specific
      urine proteomic signature able to reliably identify type 2 diabetic patients with
      diabetic glomerulosclerosis.

PMID- 20671096
TI  - Identification of two novel metabolites of SCH 486757, a nociceptin/orphanin FQ
      peptide receptor agonist, in humans.
AB  - The study of human metabolism of endo-8[bis(2-chlorophenyl)methyl]-3-(2
      pyrimidinyl)-8-azabicyclo[3.2.1]octan-3-ol (SCH 486757) after a 200-mg oral dose
      of the drug to healthy volunteers in the first-in-human study is presented. The
      structural elucidation of two unique metabolites, which were detected in the
      process of metabolite characterization in human plasma and urine by liquid
      chromatography-mass spectrometry (LC-MS), is described. These metabolites (M27
      and M34) were initially detected in human plasma at high levels (>35% of the LC
      MS response of the parent drug). Additional LC-MS experiments (hydrogen/deuterium
      exchange and accurate mass measurement) were used to determine structures of
      metabolites. It was found that both metabolites were formed through a loss of the
      C-C bridge from the tropane moiety with the conversion into a substituted
      pyridinium compound. This metabolic process has not been reported previously.
      Because of the apparent high abundance of metabolites based on the LC-MS
      response, actual circulating amounts of these metabolites relative to the parent
      drug were determined semiquantitatively to evaluate their coverage in preclinical
      species. With the use of reference standards, it was shown that the LC-MS
      response of M27 and M34 in human plasma was much higher than that of the parent
      compound. Actual amounts of M27 and M34 metabolites were less than 5% of the
      level of the parent drug; therefore, additional assessment was not required.

PMID- 20671097
TI  - Metabolism, excretion, and pharmacokinetics of oral brivanib in patients with
      advanced or metastatic solid tumors.
AB  - The goal of this study was to evaluate the pharmacokinetics, mass balance,
      metabolism, routes and extent of elimination, and safety of a single oral dose of
      (14)C-labeled brivanib alaninate and the safety and tolerability of brivanib
      after multiple doses in patients with advanced or metastatic solid tumors. This
      was a two-part, single-center, open-label, single oral-dose (part A) followed by
      multiple-dose (part B) study in patients with advanced or metastatic solid
      tumors. In part A, patients received a single dose of [(14)C]brivanib alaninate
      and in part B patients received 800 mg of nonradiolabeled brivanib alaninate
      every day. Four patients (two white, two black: two with non-small-cell lung
      cancer, one with ovarian cancer, and one with renal cell carcinoma) were treated
      in both parts. The median time to reach the maximal plasma concentration of
      brivanib was 1 h, geometric mean maximal plasma concentration was 6146 ng/ml,
      mean terminal half-life was 13.8 h, and geometric mean apparent oral clearance
      was 14.7 l/h. After a single oral dose of [(14)C]brivanib alaninate, 12.2 and
      81.5% of administered radioactivity was recovered in urine and feces,
      respectively. Brivanib alaninate was completely converted to the active moiety,
      brivanib, and the predominant route of elimination was fecal. Renal excretion of
      unchanged brivanib was minimal. Brivanib was well tolerated; fatigue was the most
      frequent adverse event occurring in all patients and the most frequent treatment
      related adverse event in three (75%). The best clinical response in one patient
      was stable disease; the other three had progressive disease. Brivanib alaninate
      was rapidly absorbed and extensively metabolized after a single 800-mg oral dose;
      the majority of drug-related radioactivity was excreted in feces.

PMID- 20671099
TI  - Motor control exercises, sling exercises, and general exercises for patients with
      chronic low back pain: a randomized controlled trial with 1-year follow-up.
AB  - BACKGROUND: Exercise benefits patients with chronic nonspecific low back pain;
      however, the most effective type of exercise remains unknown. OBJECTIVE: This
      study compared outcomes after motor control exercises, sling exercises, and
      general exercises for low back pain. DESIGN: This was a randomized controlled
      trial with a 1-year follow-up. SETTING: The study was conducted in a primary care
      setting in Norway. PATIENTS: The participants were patients with chronic
      nonspecific low back pain (n=109). INTERVENTIONS: The interventions in this study
      were low-load motor control exercises, high-load sling exercises, or general
      exercises, all delivered by experienced physical therapists, once a week for 8
      weeks. MEASUREMENTS: The primary outcome measure was pain reported on the Numeric
      Pain Rating Scale after treatment and at a 1-year follow-up. Secondary outcome
      measures were self-reported activity limitation (assessed with the Oswestry
      Disability Index), clinically examined function (assessed with the Fingertip-to
      Floor Test), and fear-avoidance beliefs after intervention. RESULTS: The
      postintervention assessment showed no significant differences among groups with
      respect to pain (overall group difference) or any of the outcome measures. Mean
      (95% confidence interval) group differences for pain reduction after treatment
      and after 1 year were 0.3 (-0.7 to 1.3) and 0.4 (-0.7 to 1.4) for motor control
      exercises versus sling exercises, 0.7 (-0.6 to 2.0) and 0.3 (-0.8 to 1.4) for
      sling exercises versus general exercises, and 1.0 (-0.1 to 2.0) and 0.7 (-0.3 to
      1.7) for motor control exercises versus general exercises. LIMITATIONS: The
      nature of the interventions made blinding impossible. CONCLUSIONS: This study
      gave no evidence that 8 treatments with individually instructed motor control
      exercises or sling exercises were superior to general exercises for chronic low
      back pain.

PMID- 20671098
TI  - Adherence to behavioral interventions for urge incontinence when combined with
      drug therapy: adherence rates, barriers, and predictors.
AB  - BACKGROUND: Behavioral intervention outcomes for urinary incontinence (UI) depend
      on active patient participation. OBJECTIVE: The purpose of this study was to
      describe adherence to behavioral interventions (pelvic-floor muscle [PFM]
      exercises, UI prevention strategies, and delayed voiding), patient-perceived
      exercise barriers, and predictors of exercise adherence in women with urge
      predominant UI. DESIGN: This was a prospectively planned secondary data analysis
      from a 2-stage, multicenter, randomized clinical trial. PATIENTS AND
      INTERVENTION: Three hundred seven women with urge-predominant UI were randomly
      assigned to receive either 10 weeks of drug therapy only or 10 weeks of drug
      therapy combined with a behavioral intervention for UI. One hundred fifty-four
      participants who received the combined intervention were included in this
      analysis. MEASUREMENTS: Pelvic-floor muscle exercise adherence and exercise
      barriers were assessed during the intervention phase and 1 year afterward.
      Adherence to UI prevention strategies and delayed voiding were assessed during
      the intervention only. RESULTS: During intervention, 81% of women exercised at
      least 5 to 6 days per week, and 87% performed at least 30 PFM contractions per
      day. Ninety-two percent of the women used the urge suppression strategy
      successfully. At the 12-month follow-up, only 32% of the women exercised at least
      5 to 6 days per week, and 56% performed 15 or more PFM contractions on the days
      they exercised. The most persistent PFM exercise barriers were difficulty
      remembering to exercise and finding time to exercise. Similarly, difficulty
      finding time to exercise persisted as a predictor of PFM exercise adherence over
      time. LIMITATIONS: Co-administration of medication for UI may have influenced
      adherence. CONCLUSIONS: Most women adhered to exercise during supervised
      intervention; however, adherence declined over the long term. Interventions to
      help women remember to exercise and to integrate PFM exercises and UI prevention
      strategies into daily life may be useful to promote long-term adherence.

PMID- 20671100
TI  - A clinical trial of neuromuscular electrical stimulation in improving quadriceps
      muscle strength and activation among women with mild and moderate osteoarthritis.
AB  - BACKGROUND: Neuromuscular electrical stimulation (NMES) has demonstrated efficacy
      in improving quadriceps muscle strength (force-generating capacity) and
      activation following knee replacement and ligamentous reconstruction. Yet, data
      are lacking to establish the efficacy of NMES in people with evidence of early
      radiographic osteoarthritis. OBJECTIVE: The purpose of this study was to
      determine whether NMES is capable of improving quadriceps muscle strength and
      activation in women with mild and moderate knee osteoarthritis. DESIGN: This
      study was a randomized controlled trial. METHODS: Thirty women with radiographic
      evidence of mild or moderate knee osteoarthritis were randomly assigned to
      receive either no treatment (standard of care) or NMES treatments 3 times per
      week for 4 weeks. The effects of NMES on quadriceps muscle strength and
      activation were evaluated upon study enrollment, as well as at 5 and 16 weeks
      after study enrollment, which represent 1 and 12 weeks after cessation of NMES
      among the treated participants. The Western Ontario and McMaster Universities
      Osteoarthritis Index and a 40-foot (12.19-m) walk test were used at each testing
      session. RESULTS: Improvements in quadriceps muscle strength or activation were
      not realized for the women in the intervention group. Quadriceps muscle strength
      and activation were similar across testing sessions for both groups. LIMITATIONS:
      Women were enrolled based on radiographic evidence of osteoarthritis, not
      symptomatic osteoarthritis, which could have contributed to our null finding. A
      type II statistical error may have been committed despite an a priori power
      calculation. The assessor and the patients were not blinded to group assignment,
      which may have introduced bias into the study. CONCLUSIONS: Four weeks of NMES
      delivered to women with mild and moderate osteoarthritis and mild strength
      deficits was insufficient to induce gains in quadriceps muscle strength or
      activation. Future research is needed to examine the dose-response relationship
      for NMES in people with early radiographic evidence of osteoarthritis.

PMID- 20671101
TI  - Can we explain heterogeneity among randomized clinical trials of exercise for
      chronic back pain? A meta-regression analysis of randomized controlled trials.
AB  - BACKGROUND: Exercise programs may vary in terms of duration, frequency, and
      dosage; whether they are supervised; and whether they include a home-based
      program. Uncritical pooling of heterogeneous exercise trials may result in
      misleading conclusions regarding the effects of exercise on chronic low back pain
      (CLBP). PURPOSE: The purpose of this study was to establish the effect of
      exercise on pain and disability in patients with CLBP, with a major aim of
      explaining between-trial heterogeneity. DATA SOURCES: Six databases were searched
      up to August 2008 using a computerized search strategy. STUDY SELECTION: Eligible
      studies needed to be randomized clinical trials evaluating the effects of
      exercise for nonspecific CLBP. Outcomes of interest were pain and disability
      measured on a continuous scale. DATA EXTRACTION: Baseline demographic data,
      exercise features, and outcome data were extracted from all included trials. DATA
      SYNTHESIS: Univariate meta-regressions were conducted to assess the associations
      between exercise effect sizes and 8 study-level variables: baseline severity of
      symptoms, number of exercise hours and sessions, supervision, individual
      tailoring, cognitive-behavioral component, intention-to-treat analysis, and
      concealment of allocation. LIMITATIONS: Only study-level characteristics were
      included in the meta-regression analyses. Therefore, the implications of the
      findings should not be used to differentiate the likelihood of the effect of
      exercise based on patient characteristics. CONCLUSIONS: The results show that, in
      general, when all types of exercise are analyzed, small but significant
      reductions in pain and disability are observed compared with minimal care or no
      treatment. Despite many possible sources of heterogeneity in exercise trials,
      only dosage was found to be significantly associated with effect sizes.

PMID- 20671102
TI  - Quantifying whole transcriptome size, a prerequisite for understanding
      transcriptome evolution across species: an example from a plant allopolyploid.
AB  - Evolutionary biologists are increasingly comparing gene expression patterns
      across species. Due to the way in which expression assays are normalized, such
      studies provide no direct information about expression per gene copy (dosage
      responses) or per cell and can give a misleading picture of genes that are
      differentially expressed. We describe an assay for estimating relative expression
      per cell. When used in conjunction with transcript profiling data, it is possible
      to compare the sizes of whole transcriptomes, which in turn makes it possible to
      compare expression per cell for each gene in the transcript profiling data set.
      We applied this approach, using quantitative reverse transcriptase-polymerase
      chain reaction and high throughput RNA sequencing, to a recently formed
      allopolyploid and showed that its leaf transcriptome was approximately 1.4-fold
      larger than either progenitor transcriptome (70% of the sum of the progenitor
      transcriptomes). In contrast, the allopolyploid genome is 94.3% as large as the
      sum of its progenitor genomes and retains > or =93.5% of the sum of its
      progenitor gene complements. Thus, "transcriptome downsizing" is greater than
      genome downsizing. Using this transcriptome size estimate, we inferred dosage
      responses for several thousand genes and showed that the majority exhibit partial
      dosage compensation. Homoeologue silencing is nonrandomly distributed across
      dosage responses, with genes showing extreme responses in either direction
      significantly more likely to have a silent homoeologue. This experimental
      approach will add value to transcript profiling experiments involving
      interspecies and interploidy comparisons by converting expression per
      transcriptome to expression per genome, eliminating the need for assumptions
      about transcriptome size.

PMID- 20671103
TI  - The influence of bicarbonate/lactate-buffered PD fluids on N{epsilon}
      (carboxyethyl)lysine and N{epsilon}-(carboxymethyl)lysine in peritoneal effluent.
AB  - OBJECTIVE: Accumulation of advanced glycation end products (AGEs) may be involved
      in the pathogenesis of peritoneal membrane dysfunction. As glycoxidation may play
      an important role in AGE formation, peritoneal dialysis fluids with low levels of
      glucose degradation products (GDPs) might result in a reduction in AGE
      concentration in the peritoneal effluent. The aim of this study was to compare
      the effects of conventional glucose-containing dialysis solutions and low GDP
      level fluids on the concentration of the AGEs N(epsilon)-(carboxymethyl)lysine
      (CML) and N(epsilon)-(carboxyethyl)lysine (CEL) in peritoneal effluent. DESIGN:
      Prospective randomized control study. METHODS: 23 patients were treated with
      either conventional glucose-containing fluid (n = 11, group A) or low level GDP
      fluid (n = 12, group B) during a period of 12 weeks. Before and after this
      period, CML and CEL were measured in peritoneal effluent. RESULTS: In groups A
      and B there were changes in CML concentrations [respectively 13.7 +/- 17.0 and 
      16.0 +/- 46.0 nmol/L (NS)] and CEL concentrations (respectively 20.3 +/- 26.6 and
      -8.8 +/- 18.9 nmol/L, p = 0.015). Residual renal function (RRF) in groups A and B
      was, respectively, 6.8 and 6.1 mL/min (NS). CML, but not CEL, in the peritoneal
      effluent was inversely related to RRF (r = -0.67, p < 0.05). CONCLUSION: CEL, but
      not CML, in the peritoneal effluent appears to be influenced by the prescription
      of low GDP level fluid, probably due to the highly reduced concentration of
      methylglyoxal, which is needed for formation of CEL. CML is primarily influenced
      by RRF.

PMID- 20671104
TI  - The impact of treatment modality on infection-related hospitalization rates in
      peritoneal dialysis and hemodialysis patients.
AB  - BACKGROUND AND OBJECTIVES: Infection is a major cause of morbidity and mortality
      in the dialysis population. This study compares the rates of infection-related
      hospitalization (IRH) in incident chronic dialysis patients initiating outpatient
      peritoneal dialysis (PD) and hemodialysis (HD). METHODS AND PATIENTS: This was a
      retrospective cohort study at the dialysis program of a tertiary-care center in
      Toronto, Canada. Incident chronic dialysis patients that were eligible for both
      PD and HD and started outpatient dialysis between 1 January 2004 and 31 August
      2008 were included. Dialysis modality was assigned at the start of outpatient
      dialysis treatment. All hospital admissions were reviewed and incidence of IRH
      was compared between PD and HD using Poisson regression. RESULTS: Of 264 incident
      chronic dialysis patients, 168 (64%) were eligible for both treatment modalities:
      71 (42%) started outpatient PD and 97 (58%) started outpatient HD. The unadjusted
      and adjusted incidence rate ratios (IRR) of IRH did not differ significantly
      between PD and HD: 1.23 [95% confidence interval (CI) 0.65-2.32, p=0.37] and 1.14
      (95% CI 0.58-2.23, p=0.71) respectively. There was no difference between PD and
      HD in the risk of access loss (28% vs 35%, p=0.73), modality change (22% vs 0%,
      p=0.10), or death (17% vs 6%, p=0.60) following hospitalization for infection.
      Patients starting outpatient treatment on PD versus HD were more likely to be
      hospitalized for peritonitis (IRR 3.20, 95% CI 1.16-9.09; p=0.029) and there was
      a trend for fewer hospitalizations for bacteremia (IRR 0.19, 95% CI 0.028-1.30;
      p=0.091). The risk of IRH did not differ between PD and HD in the subgroup of
      patients that received adequate predialysis care (IRR 1.16, 95% CI 0.59-2.27;
      p=0.67) or when patients starting outpatient HD with a central venous catheter
      were excluded (IRR 1.52, 95% CI 0.53-4.37; p=0.44). CONCLUSIONS: Patients that
      initiate outpatient peritoneal dialysis do not have a significantly increased
      risk of infection-related hospitalization compared to those that initiate
      outpatient hemodialysis.

PMID- 20671105
TI  - Efficacy of trastuzumab in routine clinical practice and after progression for
      metastatic breast cancer patients: the observational Hermine study.
AB  - BACKGROUND: The Hermine study observed the use of trastuzumab for metastatic
      breast cancer (MBC) in routine practice, including patients who received
      trastuzumab treatment beyond progression (TBP). PATIENTS AND METHODS: The study
      observed 623 patients for > or = 2 years. Treatment was given according to
      oncologists' normal clinical practices. Endpoints included duration of treatment,
      efficacy, and cardiac safety. The TBP subanalysis compared overall survival (OS)
      in 177 patients who received first-line trastuzumab and either continued
      trastuzumab for > or = 30 days following progression or stopped at or before
      progression. RESULTS: The median treatment duration was 13.3 months. In the first
      , second-, and third-line or beyond treatment groups, the median time to
      progression (TTP) were 10.3 months, 9.0 months, and 6.3 months, and the median OS
      times were 30.3 months, 27.1 months, and 23.2 months, respectively. Heart failure
      was observed in 2.6% of patients, although no cardiac-associated deaths occurred.
      In the TBP subanalysis, the median OS duration from treatment initiation and time
      of disease progression were longer in patients who continued receiving
      trastuzumab TBP (>27.8 months and 21.3 months, respectively) than in those who
      stopped (16.8 months and 4.6 months, respectively). However, the groups were not
      completely comparable, because patients who continued trastuzumab TBP had better
      prognoses at treatment initiation. The median TTP was longer in patients who
      continued trastuzumab TBP (10.2 months) than in those who stopped (7.1 months).
      CONCLUSION: The Hermine findings confirm that the pivotal trials of first-line
      trastuzumab treatment in MBC patients are applicable in clinical practice. The
      subanalysis suggests that trastuzumab TBP offers a survival benefit to MBC
      patients treated with first-line trastuzumab.

PMID- 20671106
TI  - Treatment beyond progression: is it moving from belief to evidence?

PMID- 20671107
TI  - The 12th-14th type III repeats of fibronectin function as a highly promiscuous
      growth factor-binding domain.
AB  - It has recently been shown that some growth factors (GFs) have strong
      interactions with nonproteoglycan extracellular matrix proteins. Relevant here,
      the 12th-14th type three repeats of fibronectin (FN III12-14) have been shown to
      bind insulin-like growth factor binding-protein-3, fibroblast growth factor (FGF)
      2, and vascular endothelial growth factor (VEGF)-A with high affinity. Since FN
      III12-14 is known to bind GFs from different families, we hypothesized that this
      domain could be highly promiscuous in its GF-binding capacity. We used
      biochemical approaches and surface plasmon resonance to investigate such
      interactions with recombinant FN III12-14. We found that FN III12-14 binds most
      of the GFs from the platelet-derived growth factor (PDGF)/VEGF and FGF families
      and some GFs from the transforming growth factor-beta and neurotrophin families,
      with K(D) values in the nanomolar range, without inhibiting GF activity. Overall,
      25 new binding interactions were identified. In a clinically relevant fibrin
      matrix, a fibrin-binding variant of FN III12-14 was highly effective as a GF
      delivery system. For instance, in matrices functionalized with FN III12-14, PDGF
      BB-induced sprouting of human smooth muscle cell spheroids was greatly enhanced.
      We show that FN III12-14 is a highly promiscuous ligand for GFs and also holds
      great potential in clinical healing applications.

PMID- 20671108
TI  - Transcriptional-metabolic networks in beta-carotene-enriched potato tubers: the
      long and winding road to the Golden phenotype.
AB  - Vitamin A deficiency is a public health problem in a large number of countries.
      Biofortification of major staple crops (wheat [Triticum aestivum], rice [Oryza
      sativa], maize [Zea mays], and potato [Solanum tuberosum]) with beta-carotene has
      the potential to alleviate this nutritional problem. Previously, we engineered
      transgenic "Golden" potato tubers overexpressing three bacterial genes for beta
      carotene synthesis (CrtB, CrtI, and CrtY, encoding phytoene synthase, phytoene
      desaturase, and lycopene beta-cyclase, respectively) and accumulating the highest
      amount of beta-carotene in the four aforementioned crops. Here, we report the
      systematic quantitation of carotenoid metabolites and transcripts in 24 lines
      carrying six different transgene combinations under the control of the 35S and
      Patatin (Pat) promoters. Low levels of B-I expression are sufficient for
      interfering with leaf carotenogenesis, but not for beta-carotene accumulation in
      tubers and calli, which requires high expression levels of all three genes under
      the control of the Pat promoter. Tubers expressing the B-I transgenes show large
      perturbations in the transcription of endogenous carotenoid genes, with only
      minor changes in carotenoid content, while the opposite phenotype (low levels of
      transcriptional perturbation and high carotenoid levels) is observed in Golden (Y
      B-I) tubers. We used hierarchical clustering and pairwise correlation analysis,
      together with a new method for network correlation analysis, developed for this
      purpose, to assess the perturbations in transcript and metabolite levels in
      transgenic leaves and tubers. Through a "guilt-by-profiling" approach, we
      identified several endogenous genes for carotenoid biosynthesis likely to play a
      key regulatory role in Golden tubers, which are candidates for manipulations
      aimed at the further optimization of tuber carotenoid content.

PMID- 20671109
TI  - Identification and characterization of in vitro galactosyltransferase activities
      involved in arabinogalactan-protein glycosylation in tobacco and Arabidopsis.
AB  - Arabinogalactan-proteins (AGPs) are highly glycosylated hydroxyproline (Hyp)-rich
      glycoproteins that are frequently characterized by the presence of [Alanine-Hyp]
      ([AO]) repetitive units. AGP galactosyltransferase (GalT) activities in tobacco
      (Nicotiana tabacum) and Arabidopsis (Arabidopsis thaliana) microsomal membranes
      were studied here with an in vitro GalT reaction system, which used acceptor
      substrates composed of [AO] repetitive units, specifically, a chemically
      synthesized [AO](7) acceptor and a transgenically produced and deglycosylated
      d[AO](51) acceptor. Incorporation of [(14)C]Gal from UDP-[(14)C]Gal into the
      [AO](7) and d[AO](51) acceptors was observed following HPLC fractionation of the
      reaction products. Hyp-[(14)C]Gal monosaccharide and Hyp-[(14)C]Gal disaccharide
      were identified in the base hydrolysates of the GalT reaction products,
      indicating the presence of two distinct GalT activities for the addition of the
      first and second Gal residues to the [AO] peptide in both tobacco and
      Arabidopsis. Examination of the Arabidopsis Hyp:GalT activity using various
      acceptor substrates, including two extensin sequences containing SO(4) modules
      and a [AP](7) peptide, indicated this activity was specific for peptidyl Hyp in
      AGP sequences. Mass spectrometry analysis demonstrated that only one Gal was
      added per peptide molecule to the C-terminal or penultimate Hyp residue of the
      [AO](7) peptide. In addition, [AO](7):GalT and d[AO](51):GalT activities were
      localized to the endomembrane system of Arabidopsis suspension-cultured cells
      following sucrose density gradient centrifugation. The in vitro assay reported
      here to detect GalT activities using AGP peptide and glycopeptide acceptor
      substrates provides a useful tool for the identification and verification of AGP
      specific GalT proteins/genes and an entry point for elucidation of
      arabinogalactan biosynthesis for AGPs.

PMID- 20671110
TI  - Proper levels of the Arabidopsis cohesion establishment factor CTF7 are essential
      for embryo and megagametophyte, but not endosperm, development.
AB  - CTF7 is an essential gene in yeast that is required for the formation of sister
      chromatid cohesion. While recent studies have provided insights into how sister
      chromatid cohesion is established, less is known about how specifically CTF7
      facilitates the formation of cohesion, and essentially nothing is known about how
      sister chromatid cohesion is established in plants. In this report, we describe
      the isolation and characterization of CTF7 from Arabidopsis (Arabidopsis
      thaliana). Arabidopsis CTF7 is similar to Saccharomyces cerevisiae CTF7 in that
      it lacks an amino-terminal extension, exhibits acetyltransferase activity, and
      can complement a yeast ctf7 temperature-sensitive mutation. CTF7 transcripts are
      found throughout the plant, with the highest levels present in buds. Seeds
      containing T-DNA insertions in CTF7 exhibit mitotic defects in the zygote.
      Interestingly, the endosperm developed normally in ctf7 seeds, suggesting that
      CTF7 is not essential for mitosis in endosperm nuclei. Minor defects were
      observed in female gametophytes of ctf7(+/-) plants, and plants that overexpress
      CTF7 exhibited female gametophyte lethality. Pollen development appeared normal
      in both CTF7 knockout and overexpression plants. Therefore, proper levels of CTF7
      are critical for female gametophyte and embryo development but not for the
      establishment of mitotic cohesion during microgametogenesis or during endosperm
      development.

PMID- 20671111
TI  - Vernalization-mediated VIN3 Induction Overcomes the LIKE-HETEROCHROMATIN
      PROTEIN1/POLYCOMB REPRESSION COMPLEX2-mediated epigenetic repression.
AB  - VERNALIZATION INSENSITIVE3 (VIN3) induction by vernalization is one of the
      earliest events in the vernalization response of Arabidopsis (Arabidopsis
      thaliana). However, the mechanism responsible for vernalization-mediated VIN3
      induction is poorly understood. Here, we show that the constitutive repression of
      VIN3 in the absence of the cold is due to multiple repressive components,
      including a transposable element-derived sequence, LIKE-HETEROCHROMATIN PROTEIN1
      and POLYCOMB REPRESSION COMPLEX2. Furthermore, the full extent of VIN3 induction
      by vernalization requires activating complex components, including EARLY
      FLOWERING7 and EARLY FLOWERING IN SHORT DAYS. In addition, we observed dynamic
      changes in the histone modifications present at VIN3 chromatin during the course
      of vernalization. Our results show that the induction of VIN3 includes dynamic
      changes at the level of chromatin triggered by long-term cold exposure.

PMID- 20671113
TI  - Purinergic control of neutrophil activation.
AB  - Neutrophils constitute the first line of defense against invading pathogens, but
      they also are responsible for tissue destruction in pathological conditions. In a
      recent paper published in Science Signaling, Junger and colleagues show that
      adenosine 5'-triphosphate release and signaling through purinergic P2 receptors
      upon neutrophil activation by bacterial and inflammatory stimuli represents an
      important mechanism for effective neutrophil functional response and host
      protection.

PMID- 20671112
TI  - Extracellular nucleotides elicit cytosolic free calcium oscillations in
      Arabidopsis.
AB  - Extracellular ATP induces a rise in the level of cytosolic free calcium
      ([Ca(2+)](cyt)) in plant cells. To expand our knowledge about the function of
      extracellular nucleotides in plants, the effects of several nucleotide analogs
      and pharmacological agents on [Ca(2+)](cyt) changes were studied using transgenic
      Arabidopsis (Arabidopsis thaliana) expressing aequorin or the fluorescence
      resonance energy transfer-based Ca(2+) sensor Yellow Cameleon 3.6. Exogenously
      applied CTP caused elevations in [Ca(2+)](cyt) that displayed distinct time- and
      dose-dependent kinetics compared with the purine nucleotides ATP and GTP. The
      inhibitory effects of antagonists of mammalian P2 receptors and calcium influx
      inhibitors on nucleotide-induced [Ca(2+)](cyt) elevations were distinct between
      CTP and purine nucleotides. These results suggest that distinct recognition
      systems may exist for the respective types of nucleotides. Interestingly, a
      mutant lacking the heterotrimeric G protein Gbeta-subunit exhibited a remarkably
      higher [Ca(2+)](cyt) elevation in response to all tested nucleotides in
      comparison with the wild type. These data suggest a role for Gbeta in negatively
      regulating extracellular nucleotide signaling and point to an important role for
      heterotrimeric G proteins in modulating the cellular effects of extracellular
      nucleotides. The addition of extracellular nucleotides induced multiple temporal
      [Ca(2+)](cyt) oscillations, which could be localized to specific root cells. The
      oscillations were attenuated by a vesicle-trafficking inhibitor, indicating that
      the oscillations likely require ATP release via exocytotic secretion. The results
      reveal new molecular details concerning extracellular nucleotide signaling in
      plants and the importance of fine control of extracellular nucleotide levels to
      mediate specific plant cell responses.

PMID- 20671114
TI  - Synthetic genomes for synthetic biology.
AB  - A genome synthesized entirely from scratch has been used to replace the native
      genome of a living cell, thus creating a new cell. This achievement marks a new
      frontier in synthetic biology to design and create genomes for organisms with few
      genetic tools and for applications in areas of energy, health care and the
      environment.

PMID- 20671115
TI  - RNA interference reveals a requirement for both p18INK4c and p27Kip1 in B
      lymphopoiesis.
AB  - Cyclin-dependent kinase inhibitors (CKIs) p18(INK4c) (p18) and p27(Kip1) (p27)
      were reported to be able to modulate self-renewal and differentiation of
      hematopoietic stem cells (HSCs) and hematopoietic progenitor cells, and regulate
      the lineage cell proliferation and maturation into the terminal elements;
      however, whether p18 and p27 in HSCs affect the development of lineage cells,
      especially B lymphocytes, in the reconstituted blood is unknown. Here we employed
      small-interference RNA (siRNA) technique, which provides a powerful tool for
      tissue-targeted knockdown of genes, to evaluate the biological functions of the
      p18 and p27 in the hematopoiesis process. We knocked down the expression of p18,
      p27 alone or both in the isolated sca-1(+) bone marrow cells by lentiviral vector
      based siRNA system, and transplanted these cells into lethally irradiated
      C57BL/6J mice to evaluate the effect of these two genes on reconstituted
      lymphocyte development. The knockdown of p18 or p27 alone or both was proved to
      be effective as verified by western blotting. FACS analysis results showed that
      compared with the control group, the B lymphocytes were both significantly lower
      in p18, p27 alone and especially in both p18 and p27 knockdown group in
      reconstituted peripheral blood; and the B lymphocytes showed similar trend in
      bone marrow. Interestingly, the differentiation to T cells was not greatly
      changed, only with the dramatic decrease of the CD4/CD8 ratio. Overexpression of
      the antiapoptotic protein Bcl2 could not rescue the B lymphopoiesis. All these
      results demonstrate that p18 and p27 are collaboratively involved in B
      lymphopoiesis, and simultaneous knockdown of p18 and p27 probably blocks the
      differentiation from HSCs to B lymphocytes, but not triggers apoptosis of B cell
      precursors.

PMID- 20671116
TI  - IL-15R alpha-IgG1-Fc enhances IL-2 and IL-15 anti-tumor action through NK and
      CD8+ T cells proliferation and activation.
AB  - Natural killer (NK) cells-based immunotherapy is one of the most promising
      treatments for incurable malignant tumors. NK cells in combination with
      monoclonal antibodies to surface antigens of the tumor cell have been proved to
      be effective in a number of clinical trials. A limiting step in the development
      of successful cellular immunotherapy lies in developing an efficient and economic
      method to expand appropriate amount of NK cells and CD8(+) T cells. In this
      study, we constructed a humanized IL-15Ralpha-IgG1-Fc, which mimicked IL-15 trans
      presentation. The feasibility of expanding populations of the human NK and CD8(+)
      T cells by IL-15Ralpha-IgG1-Fc complexes was tested. We then measured the
      cytotoxicity of expanded NK and CD8(+) T cells against tumor cell lines and
      primary tumor cells. When tested ex vivo, IL-2/IL-15Ralpha-IgG1-Fc complexes
      significantly enhanced NK and CD8(+) T cells expansion, isolated or non-isolated
      from PBMCs. The effect of IL-15Ralpha-IgG1-Fc was dependent on the presence of IL
      2 or IL-15. IL-15Ralpha-IgG1-Fc complexes increased NK, CD8(+) T and NKT cells
      ratio in PBMC and BMMC after 14 days incubation. High level of granzyme B
      expression was observed in the supernatant of the complexes-treated NK cells.
      Expanded NK and CD8(+) T cell populations had cytotoxic function against the PC3,
      LNCaP, K562 and chronic lymphocytic leukemia (CLL) patient primary B cell
      lymphoma. We concluded that IL-2/IL-15Ralpha-IgG1-Fc significantly enhanced NK,
      CD8(+) T and NKT cells expansion, which possess strong anti-tumor activity. These
      data support clinical testing IL-2/IL-15Ralpha-IgG1-Fc expanded NK cells in
      patients with prostate cancer and CLL.

PMID- 20671117
TI  - Association of Shp2 with phosphorylated IL-22R1 is required for interleukin-22
      induced MAP kinase activation.
AB  - Interleukin-22 (IL-22) is a member of the IL-10 family of cytokines produced by
      activated T cells and is involved in several tissue responses. IL-22 signals
      through a heterodimeric receptor composed of IL-22 receptor 1 (IL-22R1) and IL
      10R2, and the intracellular signaling pathways mediated by IL-22 receptor are not
      completely known. Here we investigate the effect of Src homology-2 containing
      protein-tyrosine phosphatase (Shp2) on IL-22 signaling pathway using SW480 colon
      cancer cells as a model. The results show that IL-22 induces IL-22R1
      phosphorylation, and Shp2 is recruited to the tyrosine phosphorylated IL-22R1
      upon IL-22 stimulation. Furthermore, Tyr251 and Tyr301 of IL-22R1 are required
      for Shp2 binding to the IL-22R1. Shp2 binding to IL-22R1 and Shp2 protein
      tyrosine phosphatase activity are required for activation of MAP kinases and
      signal transducer and activator of transcription (STAT3) phosphorylation by IL
      22. These results reveal a critical role of Shp2 in IL-22 mediated signal
      transduction pathways.

PMID- 20671118
TI  - A novel latent membrane 2 transcript expressed in Epstein-Barr virus-positive NK-
      and T-cell lymphoproliferative disease encodes a target for cellular
      immunotherapy.
AB  - Therapeutic targeting of virus-encoded proteins using cellular immunotherapy has
      proved successful for Epstein-Barr virus (EBV)-associated posttransplant
      lymphoproliferative disease. However, the more limited repertoire and
      immunogenicity of EBV-encoded proteins in other malignancies such as Hodgkin
      lymphoma and extranodal natural killer (NK)/T lymphoma has been more challenging
      to target. The immunosubdominant latent membrane protein 2 (LMP2) is considered
      the optimal target in such Latency II tumors, although data relating to its
      expression in T/NK malignancies are limited. In addressing the validity of LMP2
      as an immunotherapeutic target we found that LMP2-specific effector CD8(+) T
      cells recognized and killed EBV-positive NK- and T-cell tumor lines, despite an
      apparent absence of LMP2A protein and barely detectable levels of LMP2
      transcripts from the conventional LMP2A and LMP2B promoters. We resolved this
      paradox by identifying in these lines a novel LMP2 mRNA, initiated from within
      the EBV terminal repeats and containing downstream, epitope-encoding exons. This
      same mRNA was also highly expressed in primary (extra-nodal) NK/T lymphoma
      tissue, with virtually undetectable levels of conventional LMP2A/B transcripts.
      Expression of this novel transcript in T/NK-cell lymphoproliferative diseases
      validates LMP2 as an attractive target for cellular immunotherapy and implicates
      this truncated LMP2 protein in NK- and T-cell lymphomagenesis. This study is
      registered at clinicaltrials.gov as NCT00062868.

PMID- 20671119
TI  - Contributions of TRAIL-mediated megakaryocyte apoptosis to impaired megakaryocyte
      and platelet production in immune thrombocytopenia.
AB  - Recent in vitro studies provide evidence for autoantibody-induced suppression of
      megakaryocytopoiesis and show a reduction in megakaryocyte production and
      maturation in the presence of immune thrombocytopenia (ITP) plasma. Here, we
      present CD34(+) cells from healthy umbilical cord blood mononuclear cells
      cultured in medium containing thrombopoietin, stem cell factor, interleukin-3,
      and 10% plasma from either ITP patients or healthy subjects. The quantity,
      quality, and apoptosis of megakaryocytes were measured. We observed that most ITP
      plasma boosted megakaryocyte quantity but impaired quality, resulting in
      significantly less polyploidy cells (N >= 4) and platelet release. In these
      megakaryocytes, we found a lower percentage of cell apoptosis, a lower expression
      of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), and a higher
      expression of Bcl-xL. Furthermore, there was a decrease of sTRAIL in ITP plasma
      and in cell culture supernatants of this group compared with the control group.
      Our findings suggest that decreased apoptosis of megakaryocytes also contributes
      to in vitro dysmegakaryocytopoiesis and reduced platelet production. The abnormal
      expression of sTRAIL in plasma and TRAIL and Bcl-xL in megakaryocytes may play a
      role in the pathogenesis of impaired megakaryocyte apoptosis in ITP.

PMID- 20671120
TI  - Interleukin-23 acts as antitumor agent on childhood B-acute lymphoblastic
      leukemia cells.
AB  - Interleukin (IL)-23 is a proinflammatory cytokine belonging to the IL-12
      superfamily. The antitumor activity of IL-23 is controversial, and it is unknown
      whether or not the cytokine can act directly on tumor cells. The aim of this
      study was to investigate the potential direct antitumor activity of IL-23 in
      pediatric B-acute lymphoblastic leukemia (B-ALL) cells and to unravel the
      molecular mechanisms involved. Here, we show, for the first time, that IL-23R is
      up-regulated in primary B-ALL cells, compared with normal early B lymphocytes,
      and that IL-23 dampens directly tumor growth in vitro and in vivo through the
      inhibition of tumor cell proliferation and induction of apoptosis. The latter
      finding is related to IL-23-induced up-regulation of miR15a expression and the
      consequent down-regulation of BCL-2 protein expression in pediatric B-ALL cells.
      This study demonstrates that IL-23 possesses antileukemic activity and unravels
      the underlying mechanisms. Thus, IL-23 may be a candidate novel drug for the
      treatment of B-ALL patients unresponsive to current therapeutic standards.

PMID- 20671121
TI  - Targeting of survivin by nanoliposomal ceramide induces complete remission in a
      rat model of NK-LGL leukemia.
AB  - The natural killer (NK) type of aggressive large granular lymphocytic (LGL)
      leukemia is a fatal illness that pursues a rapid clinical course. There are no
      effective therapies for this illness, and pathogenetic mechanisms remain
      undefined. Here we report that the survivin was highly expressed in both
      aggressive and chronic leukemic NK cells but not in normal NK cells. In vitro
      treatment of human and rat NK-LGL leukemia cells with cell-permeable, short-chain
      C6-ceramide (C6) in nanoliposomal formulation led to caspase-dependent apoptosis
      and diminished survivin protein expression, in a time- and dose-dependent manner.
      Importantly, systemic intravenous delivery of nanoliposomal ceramide induced
      complete remission in the syngeneic Fischer F344 rat model of aggressive NK-LGL
      leukemia. Therapeutic efficacy was associated with decreased expression of
      survivin in vivo. These data suggest that in vivo targeting of survivin through
      delivery of nanoliposomal C6-ceramide may be a promising therapeutic approach for
      a fatal leukemia.

PMID- 20671122
TI  - Human NK cells of mice with reconstituted human immune system components require
      preactivation to acquire functional competence.
AB  - To investigate human natural killer (NK)-cell reactivity in vivo we have
      reconstituted human immune system components by transplantation of human
      hematopoietic progenitor cells into NOD-scid IL2Rgamma(null) mice. We demonstrate
      here that this model allows the development of all NK-cell subsets that are also
      found in human adult peripheral and cord blood, including NKp46(+)CD56(-) NK
      cells. Similar to human cord blood, NK cells from these reconstituted mice
      require preactivation by interleukin-15 to reach the functional competence of
      human adult NK cells. Mainly the terminally differentiated CD16(+) NK cells
      demonstrate lower reactivity without this stimulation. After preactivation, both
      CD16(+) and CD16(-) NK cells efficiently produce interferon-gamma and degranulate
      in response to stimulation with NK cell-susceptible targets, including K562
      erythroleukemia cells. NK-cell lines, established from reconstituted mice,
      demonstrate cytotoxicity against this tumor cell line. Importantly, preactivation
      can as well be achieved by bystander cell maturation via poly I:C stimulation in
      vitro and injection of this maturation stimulus in vivo. Preactivation in vivo
      enhances killing of human leukocyte antigen class I negative tumor cells after
      their adoptive transfer. These data suggest that a functional, but resting, NK
      cell compartment can be established in immune-compromised mice after human
      hematopoietic progenitor cell transfer.

PMID- 20671123
TI  - IkappaB kinase overcomes PI3K/Akt and ERK/MAPK to control FOXO3a activity in
      acute myeloid leukemia.
AB  - The FOXO transcription factors are involved in multiple signaling pathways and
      have tumor-suppressor functions. In acute myeloid leukemia (AML), deregulation of
      oncogenic kinases, including Akt, extra-signal-regulated kinase, or IkappaB
      kinase, is frequently observed, which may potentially inactivate FOXO activity.
      We therefore investigated the mechanism underlying the regulation of FOXO3a, the
      only FOXO protein constantly expressed in AML blast cells. We show that in both
      primary AML samples and in a MV4-11/FOXO3a-GFP cell line, FOXO3a is in a constant
      inactive state due to its cytoplasmic localization, and that neither PI3K/Akt nor
      extra-signal-regulated kinase-specific inhibition resulted in its nuclear
      translocation. In contrast, the anti-Nemo peptide that specifically inhibits IKK
      activity was found to induce FOXO3a nuclear localization in leukemic cells.
      Furthermore, an IKK-insensitive FOXO3a protein mutated at S644 translocated into
      the nucleus and activated the transcription of the Fas-L and p21(Cip1) genes.
      This, in turn, inhibited leukemic cell proliferation and induced apoptosis. These
      results thus indicate that IKK activity maintains FOXO3a in the cytoplasm and
      establishes an important role of FOXO3a inactivation in the proliferation and
      survival of AML cells. The restoration of FOXO3a activity by interacting with its
      subcellular distribution may thus represent a new attractive therapeutic strategy
      for AML.

PMID- 20671128
TI  - Review of the complexities of the PI3K/mTOR pathway presages similar handling of
      other critical topics.

PMID- 20671124
TI  - Outcomes of pediatric bone marrow transplantation for leukemia and myelodysplasia
      using matched sibling, mismatched related, or matched unrelated donors.
AB  - Although some trials have allowed matched or single human leukocyte antigen (HLA)
      mismatched related donors (mmRDs) along with HLA-matched sibling donors (MSDs)
      for pediatric bone marrow transplantation in early-stage hematologic
      malignancies, whether mmRD grafts lead to similar outcomes is not known. We
      compared patients < 18 years old reported to the Center for International Blood
      and Marrow Transplant Research with acute myeloid leukemia, acute lymphoblastic
      leukemia, chronic myeloid leukemia, and myelodysplastic syndrome undergoing
      allogeneic T-replete, myeloablative bone marrow transplantation between 1993 and
      2006. In total, patients receiving bone marrow from 1208 MSDs, 266 8/8 allelic
      matched unrelated donors (URDs), and 151 0-1 HLA-antigen mmRDs were studied.
      Multivariate analysis showed that recipients of MSD transplants had less
      transplantation-related mortality, acute graft-versus-host disease (GVHD), and
      chronic GVHD, along with better disease-free and overall survival than the URD
      and mmRD groups. No differences were observed in transplant-related mortality,
      acute and chronic GVHD, relapse, disease-free survival, or overall survival
      between the mmRD and URD groups. These data show that mmRD and 8/8 URD outcomes
      are similar, whereas MSD outcomes are superior to the other 2 sources. Whether
      allele level typing could identify mmRD recipients with better outcomes will not
      be known unless centers alter practice and type mmRD at the allele level.

PMID- 20671131
TI  - Angiopoietin-2 in CLL.

PMID- 20671130
TI  - I don't know how to treat amyloidosis.

PMID- 20671132
TI  - Want fries with that? Antimyeloma drug combos.

PMID- 20671133
TI  - A day (or 5) in a neutrophil's life.

PMID- 20671134
TI  - Inside bloody lymphatics.

PMID- 20671135
TI  - The TSH-free thyroxine relationship: logarithmic--linear or error function?

PMID- 20671137
TI  - Asthma, asthma medications, and prostate cancer risk.
AB  - BACKGROUND: The aim of this study was to assess whether a history of asthma or
      the use of asthma medications is associated with prostate cancer risk. METHODS:
      Of 16,934 men participating in the Melbourne Collaborative Cohort Study, 1,179
      were diagnosed with prostate cancer during an average follow-up of 13.4 years to
      the end of December 2007. Information on asthma history was obtained at baseline
      interview. Participants were asked to bring their current medications to the
      study center. The names of the drugs were entered into a form and coded. Asthma
      medications were categorized into four groups and corresponding hazard ratios
      (HR) were estimated from Cox regression models adjusted for country of birth.
      RESULTS: Asthma was associated with a small increase in prostate cancer risk [HR
      1.25; 95% confidence interval (95% CI), 1.05-1.49]. The HRs for use of
      medications were 1.39 (95% CI, 1.03-1.88) for inhaled glucocorticoids, 1.71 (95%
      CI, 1.08-2.69) for systemic glucocorticoids, 1.36 (95% CI, 1.05-1.76) for
      bronchodilators, and 0.78 (95% CI, 0.45-1.35) for antihistamines. The HRs for
      asthma and asthma medication use changed only slightly after mutual adjustment.
      CONCLUSIONS: A history of asthma and the use of asthma medications, particularly
      systemic glucocorticoids, are associated with an increased risk of prostate
      cancer, although it is difficult to disentangle the effects of asthma medications
      from those of asthma per se. IMPACT: These findings, if confirmed in independent
      studies, might lead to the identification of new risk factors for prostate
      cancer.

PMID- 20671136
TI  - Prospective study of human papillomavirus (HPV) types, HPV persistence, and risk
      of squamous cell carcinoma of the cervix.
AB  - BACKGROUND: The link between squamous cell cervical carcinoma and human
      papillomavirus (HPV) 16/18 is well established, but the magnitude of the risk
      association is uncertain and the importance of other high-risk HPV (HRHPV) types
      is unclear. METHODS: In two prospective nested case-control series among women
      participating in cytologic screening in Sweden, we collected 2,772 cervical
      smears from 515 women with cancer in situ (CIS), 315 with invasive squamous cell
      carcinoma (SCC), and individually matched controls. All smears were tested for
      HPV with PCR assays, and the median follow-up until diagnosis was 5 to 7 years.
      Conditional logistic regression was used to estimate relative risks (RR) and 95%
      confidence intervals (95% CI). RESULTS: The presence of HPV16/18 in the first
      smear was associated with 8.5-fold (95% CI, 5.3-13.7) and 18.6-fold (95% CI, 9.0
      38.9) increased risks of CIS and SCC, respectively, compared with women negative
      for HPV. Infection with other HRHPV types in the first smear was also associated
      with significantly increased risks for both CIS and SCC. Persistence of HPV16
      infection conferred a RR of 18.5 (95% CI, 6.5-52.9) for CIS and 19.5 (95% CI, 4.7
      81.7) for SCC. The HPV16/18 attributable risk proportion was estimated at 30% to
      50% for CIS, and 41% to 47% for SCC. Other HRHPV types also conferred significant
      proportions. CONCLUSIONS: Our large population-based study provides
      quantification of risks for different HPV types and prospective evidence that non
      16/18 HRHPV types increase the risk for future cervical cancer. IMPACT: This
      study gives further insights into cervical cancer risk stratification with
      implications for HPV-based prevention strategies.

PMID- 20671138
TI  - G708E mutation in the androgen receptor results in complete loss of androgen
      function.
AB  - End-organ resistance to androgens, called androgen insensitivity syndrome (AIS),
      is a rare disorder. The most common cause of AIS is mutations(s) in the androgen
      receptor (AR) gene; however, a significant number of these mutations have not
      been functionally analyzed. In the present study, we analyzed a case of complete
      AIS for mutations in the AR gene. Sequencing of the entire coding region of the
      AR gene revealed a 2650G>A mutation (mRNA sequence reference) in exon 4 of the
      gene, resulting in replacement of glycine with glutamate at codon 708 in the
      ligand-binding domain of the AR protein. The mutation was absent in 200 normal
      male individuals analyzed to look at its occurrence in general population. In
      vitro androgen-binding and transactivation assays showed that the mutation
      resulted in approximately 65% loss of ligand binding and almost complete loss of
      transactivation function. Complete AIS in this individual was due to a G708E
      substitution in the AR protein.

PMID- 20671139
TI  - Self-reported premature ejaculation prevalence and characteristics in Korean
      young males: community-based data from an internet survey.
AB  - Premature ejaculation (PE) is suspected to be the most prevalent male sexual
      complaint, and the prevalence of PE is considerably high also in the younger
      generation. We investigated the PE prevalence based on the Diagnostic and
      Statistical Manual of Mental Disorders (4th ed text revision; DSM-IV-TR)
      definition and the risk factors of PE in Korean young men via Internet survey.
      Subjects (n = 3980) aged from 20 to 59, who performed sexual intercourse more
      than once a month during the past 6 months were asked to participate in this
      study. Participants were asked to complete a questionnaire that consisted of
      questions on general, medical, and sexual history related to ejaculation. A total
      of 600 subjects were included in this study. PE prevalence was found to be 18.3%.
      Prevalences were not significantly different across age groups, after excluding
      subjects with erectile dysfunction (ED). Educational level, marital status and
      duration, average income, sexual orientation, smoking, alcohol consumption, and
      circumcision status showed no difference in the PE and non-PE groups. Partners
      perceived satisfaction rates were 45.0% in the PE group and 63.9% in the non-PE
      group. Significant differences were found between the PE and non-PE groups in
      terms of ED, obesity, and depression prevalence. However, multiple logistic
      regression analysis revealed that the significant risk factors of PE were age and
      the frequency of conversations with partners about sexual intercourse. This
      Internet-based study is limited because participants probably represent a
      selected population of Internet users with non-representative educational and
      socioeconomic profiles. This study is the first to report the prevalence of both
      self-reported PE and PE on the basis of the DSM-IV-TR definition in the Korean
      population. This study demonstrates that PE in Korea is as prevalent as it is in
      European countries and the United States.

PMID- 20671140
TI  - Reduced vasoreactivity in corpus cavernosum of the akita mouse.
AB  - Diabetes Mellitus (DM) is an important risk factor of erectile dysfunction (ED).
      We sought to investigate the nature and mechanism of the vasoreactivity in Akita
      (Ins2 [WT/C96Y]) mice, a model of genetic nonobese Type 1 diabetes that
      recapitulates human Type 1 diabetes. Eight wild-type (WT) mice (group 1) and 8
      Akita mice (group 2) were used for this study. Corporal tissues were harvested
      and studied for endothelium-dependent and endothelium-independent
      vasoreactivities by isometric tension study; levels of vascular endothelial
      growth factor (VEGF) and cyclic guanosine monophosphate (cGMP) were studied with
      the use of enzyme-linked immunosorbent assay (ELISA). Endothelium-dependent and
      endothelium-independent vasoreactivities, cGMP, and VEGF were significantly
      decreased in the corporal tissues of Akita mice. Corporal tissues from Akita mice
      demonstrate many of the major functional and biochemical changes found in humans
      with ED. This model could serve as a valuable tool for advancing our
      understanding of the role DM plays in the pathogenesis of ED.

PMID- 20671141
TI  - Natural course of severe oligozoospermia in infertile male: influence on future
      fertility potential.
AB  - Most couples with severe male factor infertility are treated with assisted
      reproduction technology and little has been known about the prognosis of severe
      male factor infertility itself. We investigated the prognosis of infertile male
      patients with severe oligozoospermia. Thirty-nine patients with severe
      nonobstructive oligozoospermia were followed more than 6 months without any
      medical or surgical intervention. Retrospective analyses of the natural sequence
      of the condition and influences on the future fertility potential of the study
      participants were conducted. Sperm concentration, motility, and morphology
      between first semen analysis and last semen analysis were not significantly
      different. However, during the follow-up period, 5 (12.8%) patients became
      azoospermic. In 7 (17.9%) patients, the sperm count declined to a severe level
      that could be detected only after centrifugation. Three patients underwent
      microdissection testicular sperm extraction (TESE) for sperm retrieval after
      confirmation of azoospermia. The sperm retrieval was successful only in 1 of the
      3 patients. Therefore, male patients diagnosed with severe oligozoospermia should
      be informed about possible aggravation of their residual spermatogenesis function
      and the necessity of intermittent follow-up semen analyses. If follow-up semen
      tests show a declining tendency, sperm cryopreservation may be recommended for
      these patients. If azoospermia develops during the follow-up period, early TESE
      procedure should be considered to improve the chance of sperm retrieval.

PMID- 20671142
TI  - Replication needed to detect alterations in the composition of rodent, rabbit, or
      human testes via volume density approaches.
AB  - Sperm production is an important variable affecting the reproductive capacity of
      men and other male mammals. Because spermatogenesis is highly susceptible to
      disruption, volume density techniques that enable the composition of testicular
      tissue to be characterized or sperm production rates to be quantified are used
      extensively to assess potential impacts of known or suspected reproductive
      toxins, the safety of proposed human or animal drugs, and basic studies on
      spermatogenesis in normal individuals. The number of subjects used per treatment
      group for such studies has been variable. However, the power and sensitivity of
      any experiment is dependent on the inherent variability associated with the end
      point(s) of interest and the number of replicates (ie, animals or men per
      treatment group) employed per treatment group. Because the reliability of one's
      experimental outcome should be of utmost consideration, it is important to
      characterize the typical levels of inherent variability associated with one's
      chosen end point(s) and to answer the question: how many subjects are required
      per treatment group to provide an experiment with a given power and sensitivity
      for detecting actual treatment effects? This study was undertaken to 1)
      characterize the inherent variability associated with the volume density of
      several testicular components in rodents, rabbits, and humans and among cell
      numbers derived from volume density data and 2) identify the approximate number
      of replicates that would be required to provide future studies of predictable
      power and sensitivity for which data were to be generated via the volume density
      approach. Replication requirements differed, sometimes by several orders of
      magnitude, among these species and among end points within a single species. In
      addition, for many of these species and end points, the number of replicates
      necessary to ensure modest power and sensitivity for detecting treatment
      differences exceeded that used in most investigations. These findings are
      discussed in relation to the design and interpretation of future investigations
      with these species and end points.

PMID- 20671143
TI  - Long-term effect of microsurgical inguinal varicocelectomy on testicular blood
      flow.
AB  - We aimed to investigate the long-term effect of microsurgical inguinal
      varicocelectomy on testicular blood flow using color Doppler sonography (CDS) in
      this observational study. A total of 30 patients clinically diagnosed with left
      varicocele who underwent a microsurgical inguinal varicocelectomy were examined 3
      times with CDS for testicular blood flow parameters, first before, then 3 months
      after, and finally 6 months after the operation. CDS values of testicular blood
      flow (peak systolic velocity, end diastolic velocity, resistive index, and
      pulsatility index) were measured from testicular, capsular, and intratesticular
      arteries. We also evaluated preoperative and postoperative semen parameters. The
      mean values of blood flow velocities in the left testicular artery (peak systolic
      and end diastolic) increased and resistance indices (resistive and pulsatility)
      in the left capsular and intratesticular arteries decreased significantly after
      surgery (P < .05). No significant difference was detected between the
      preoperative and postoperative blood flow parameters in the right testicular,
      capsular, or intratesticular arteries (P < .05). In the semen analysis run 3
      months after the operations, statistically significant increases were found in
      sperm concentration (P < .001), morphology percentage (P < .001), and total
      motile sperm concentration (P = .009). The increase in blood flow velocity in the
      testicular artery and the decrease in resistive and pulsatility indices in the
      capsular and intratesticular branches of the artery may be strong indicators of
      an increase in testicular arterial blood flow into the testicular tissue. Our
      data show that a significant improvement occurs in testicular blood supply and
      sperm parameters after microsurgical inguinal varicocelectomy.

PMID- 20671144
TI  - Cyclooxygenase-2 protects germ cells against spermatogenesis disturbance in
      experimental cryptorchidism model mice.
AB  - The role of cyclooxygenases (COX) in the male reproductive organ remains unclear.
      However, there are some reports suggesting that COX-2 might have an effect on
      spermatogenesis or steroidogenesis. In this study, we examined whether COX-2 was
      induced in impaired testes, and we also investigated the possible role of COX in
      the testes using experimental cryptorchidism model mice. Five-week-old male mice
      underwent an operation to induce unilateral cryptorchidism via an abdominal
      incision and suturing of the left testes to the lateral abdominal wall, and they
      were then divided into 3 groups: 1) experimental cryptorchidism plus SC560
      (selective COX-1 inhibitor) administration; 2) experimental cryptorchidism plus
      NS398 (selective COX-2 inhibitor) administration; 3) and experimental
      cryptorchidism alone. The expression levels of COX-1 and COX-2 were determined by
      immunohistologic staining and quantitative reverse transcription-polymerase chain
      reaction (RT-PCR). The influence of COX inhibitors on the testes was assessed by
      measuring the concentration of serum testosterone and evaluating the seminiferous
      tubules according to the Johnsen score. Terminal deoxynucleotidyl transferase
      mediated dUTP-biotin nick-end labeling (TUNEL) staining was also performed to
      detect apoptosis in the testes. Immunohistologic staining and RT-PCR revealed
      that the expression of COX-2 was increased in the experimental cryptorchid testes
      (groups 1-3). The concentration of serum testosterone was significantly lower in
      group 2 at 5 weeks after surgery than in the other groups. The Johnsen score of
      the cryptorchid testes in group 2 was significantly lower than those in other
      groups at 5 weeks after surgery. TUNEL staining revealed that the number of
      apoptotic cells was significantly increased in group 2 compared with the other
      groups. However, the COX-1 inhibitor did not appear to affect spermatogenesis in
      the experimental cryptorchid testes. These results suggest that the COX-2
      inhibitor provoked testicular damage in experimental cryptorchidism by inducing
      germ cell apoptosis. The expression of COX-2 might be induced to protect germ
      cells from heat stress caused by experimental cryptorchidism.

PMID- 20671145
TI  - The importance and validity of technical assumptions required for quantifying
      sperm production rates: a review.
AB  - All approaches for quantifying treatment effects on sperm production require one
      or more technical assumptions. Their validity can impact the integrity of the
      resulting data, but most had not been subjected to thorough, critical
      examination. This review was undertaken to 1) identify the assumptions required
      with each of several popular histometric methods for quantifying treatment
      effects on sperm production, 2) cite examples in which each assumption had
      failed, 3) assess potential consequences of the failure of each technical
      assumption, and 4) consider safeguards by which one might avoid misleading
      outcomes in the event that a specific assumption did not hold.

PMID- 20671147
TI  - MetNetMaker: a free and open-source tool for the creation of novel metabolic
      networks in SBML format.
AB  - An application has been developed to help with the creation and editing of
      Systems Biology Markup Language (SBML) format metabolic networks up to the
      organism scale. Networks are defined as a collection of Kyoto Encyclopedia of
      Genes and Genomes (KEGG) LIGAND reactions with an optional associated Enzyme
      Classification (EC) number for each reaction. Additional custom reactions can be
      defined by the user. Reactions within the network can be assigned flux
      constraints and compartmentalization is supported for each reaction in addition
      to the support for reactions that occur across compartment boundaries. Exported
      networks are fully SBML L2V4 compatible with an optional L2V1 export for
      compatibility with old versions of the COBRA toolbox. AVAILABILITY AND
      IMPLEMENTATION: The software runs in the free Microsoft Access 2007 Runtime
      (Microsoft Inc.), which is included with the installer and works on Windows XP
      SP2 or better. Full source code is viewable in the full version of Access 2007 or
      2010. Users must have a license to use the KEGG LIGAND database (free academic
      licensing is available). Please go to
      www.bioinformatics.leeds.ac.uk/~pytf/metnetmaker for software download, help and
      tutorials.

PMID- 20671146
TI  - The shift from a response strategy to object-in-place strategy during learning is
      accompanied by a matching shift in neural firing correlates in the hippocampus.
AB  - Hippocampal-dependent tasks often involve specific associations among stimuli
      (including egocentric information), and such tasks are therefore prone to
      interference from irrelevant task strategies before a correct strategy is found.
      Using an object-place paired-associate task, we investigated changes in neural
      firing patterns in the hippocampus in association with a shift in strategy during
      learning. We used an object-place paired-associate task in which a pair of
      objects was presented in two different arms of a radial maze. Each object was
      associated with reward only in one of the arms, thus requiring the rats to
      consider both object identity and its location in the maze. Hippocampal neurons
      recorded in CA1 displayed a dynamic transition in their firing patterns during
      the acquisition of the task across days, and this corresponded to a shift in
      strategy manifested in behavioral data. Specifically, before the rats learned the
      task, they chose an object that maintained a particular egocentric relationship
      with their body (response strategy) irrespective of the object identity. However,
      as the animal acquired the task, it chose an object according to both its
      identity and the associated location in the maze (object-in-place strategy). We
      report that CA1 neurons in the hippocampus changed their prospective firing
      correlates according to the dominant strategy (i.e., response versus object-in
      place strategy) employed at a given stage of learning. The results suggest that
      neural firing pattern in the hippocampus is heavily influenced by the task demand
      hypothesized by the animal and the firing pattern changes flexibly as the
      perceived task demand changes.

PMID- 20671148
TI  - Correction of mass calibration gaps in liquid chromatography-mass spectrometry
      metabolomics data.
AB  - MOTIVATION: High mass accuracy is an important goal in liquid chromatography-mass
      spectrometry experiments. Some manufacturers employ a mass calibration system
      that regularly switches between the analyte and a standard reference compound,
      and leads to gaps in the analyte data. We present a method for correction of such
      gaps in global molecular profiling applications such as metabolomics. We
      demonstrate that it improves peak detection and quantification, successfully
      recovering the expected number of peaks and intensity distribution in an example
      metabolomics dataset. AVAILABILITY AND IMPLEMENTATION: Available in XCMS versions
      1.23.3 and higher. Distributed via Bioconductor under GNU General Public License.
      (http://www.bioconductor.org/packages//2.7/bioc/html/xcms.html).

PMID- 20671149
TI  - ExpressionView--an interactive viewer for modules identified in gene expression
      data.
AB  - SUMMARY: ExpressionView is an R package that provides an interactive graphical
      environment to explore transcription modules identified in gene expression data.
      A sophisticated ordering algorithm is used to present the modules with the
      expression in a visually appealing layout that provides an intuitive summary of
      the results. From this overview, the user can select individual modules and
      access biologically relevant metadata associated with them. AVAILABILITY:
      http://www.unil.ch/cbg/ExpressionView. Screenshots, tutorials and sample data
      sets can be found on the ExpressionView web site.

PMID- 20671150
TI  - TreesimJ: a flexible, forward time population genetic simulator.
AB  - MOTIVATION: Most population genetic simulators fall into one of two classes,
      backward time simulators that quickly generate trees but accommodate only
      relatively simple selective and demographic regimes, and forward simulators that
      allow for a broader range of evolutionary scenarios but which cannot produce
      genealogies. Thus, few tools are available that allow for producing genealogies
      under arbitrarily complex selective and demographic models. RESULTS: TreesimJ is
      a forward time population genetic simulator that allows for sampling of
      genealogies, genetic data and many population parameters from populations
      evolving under complex evolutionary scenarios. The application provides many
      fitness and demographic models and new models are easy to develop. Data
      collection is performed by a variety of independently configurable collectors
      which periodically sample the population and record statistics. Output options
      include writing traces, histograms and summary statistics from the data
      collectors in addition to sampled genetic sequences and genealogies. SUMMARY:
      TreesimJ allows researchers to easily sample and analyze gene genealogies and
      related data from populations evolving under a wide variety of selective and
      demographic regimes. It is likely to be useful for population genetic researchers
      seeking to understand the links between evolutionary and demographic forces,
      genealogical structure and the resulting patterns of genetic variation.
      AVAILABILITY: TreesimJ home : http://staff.washington.edu/brendano/treesimj.
      Source and developer resources: http://code.google.com/p/treesimj.

PMID- 20671151
TI  - Datamonkey 2010: a suite of phylogenetic analysis tools for evolutionary biology.
AB  - Datamonkey is a popular web-based suite of phylogenetic analysis tools for use in
      evolutionary biology. Since the original release in 2005, we have expanded the
      analysis options to include recently developed algorithmic methods for
      recombination detection, evolutionary fingerprinting of genes, codon model
      selection, co-evolution between sites, identification of sites, which rapidly
      escape host-immune pressure and HIV-1 subtype assignment. The traditional
      selection tools have also been augmented to include recent developments in the
      field. Here, we summarize the analyses options currently available on Datamonkey,
      and provide guidelines for their use in evolutionary biology. Availability and
      documentation: http://www.datamonkey.org.

PMID- 20671152
TI  - PTIP promotes chromatin changes critical for immunoglobulin class switch
      recombination.
AB  - Programmed genetic rearrangements in lymphocytes require transcription at antigen
      receptor genes to promote accessibility for initiating double-strand break (DSB)
      formation critical for DNA recombination and repair. Here, we showed that
      activated B cells deficient in the PTIP component of the MLL3 (mixed-lineage
      leukemia 3)-MLL4 complex display impaired trimethylation of histone 3 at lysine 4
      (H3K4me3) and transcription initiation of downstream switch regions at the
      immunoglobulin heavy-chain (Igh) locus, leading to defective immunoglobulin class
      switching. We also showed that PTIP accumulation at DSBs contributes to class
      switch recombination (CSR) and genome stability independently of Igh switch
      transcription. These results demonstrate that PTIP promotes specific chromatin
      changes that control the accessibility of the Igh locus to CSR and suggest a
      nonredundant role for the MLL3-MLL4 complex in altering antibody effector
      function.

PMID- 20671153
TI  - Planar cell polarity acts through septins to control collective cell movement and
      ciliogenesis.
AB  - The planar cell polarity (PCP) signaling pathway governs collective cell
      movements during vertebrate embryogenesis, and certain PCP proteins are also
      implicated in the assembly of cilia. The septins are cytoskeletal proteins
      controlling behaviors such as cell division and migration. Here, we identified
      control of septin localization by the PCP protein Fritz as a crucial control
      point for both collective cell movement and ciliogenesis in Xenopus embryos. We
      also linked mutations in human Fritz to Bardet-Biedl and Meckel-Gruber syndromes,
      a notable link given that other genes mutated in these syndromes also influence
      collective cell movement and ciliogenesis. These findings shed light on the
      mechanisms by which fundamental cellular machinery, such as the cytoskeleton, is
      regulated during embryonic development and human disease.

PMID- 20671154
TI  - Land-level changes produced by the Mw 8.8 2010 Chilean earthquake.
AB  - We observed vertically displaced coastal and river markers after the 27 February
      2010 Chilean earthquake [moment magnitude (Mw) 8.8]. Land-level changes range
      between 2.5 and -1 meters, evident along an approximately 500-kilometers-long
      segment identified here as the maximum length of coseismic rupture. A hinge line
      located 120 kilometers from the trench separates uplifted areas, to the west,
      from subsided regions. A simple elastic dislocation model fits these observations
      well; model parameters give a similar seismic moment to seismological estimates
      and suggest that most of the plate convergence since the 1835 great earthquake
      was elastically stored and then released during this event.

PMID- 20671155
TI  - Quantum oscillations and hall anomaly of surface states in the topological
      insulator Bi2Te3.
AB  - Topological insulators are insulating materials that display massless, Dirac-like
      surface states in which the electrons have only one spin degree of freedom on
      each surface. These states have been imaged by photoemission, but little
      information on their transport parameters, for example, mobility, is available.
      We report the observation of Shubnikov-de Haas oscillations arising from the
      surface states in nonmetallic crystals of Bi(2)Te(3). In addition, we uncovered a
      Hall anomaly in weak fields, which enables the surface current to be seen
      directly. Both experiments yield a surface mobility (9000 to 10,000 centimeter(2)
      per volt-second) that is substantially higher than in the bulk. The Fermi
      velocity of 4 x 10(5) meters per second obtained from these transport experiments
      agrees with angle-resolved photoemission experiments.

PMID- 20671156
TI  - FAN1 acts with FANCI-FANCD2 to promote DNA interstrand cross-link repair.
AB  - Fanconi anemia (FA) is caused by mutations in 13 Fanc genes and renders cells
      hypersensitive to DNA interstrand cross-linking (ICL) agents. A central event in
      the FA pathway is mono-ubiquitylation of the FANCI-FANCD2 (ID) protein complex.
      Here, we characterize a previously unrecognized nuclease, Fanconi anemia
      associated nuclease 1 (FAN1), that promotes ICL repair in a manner strictly
      dependent on its ability to accumulate at or near sites of DNA damage and that
      relies on mono-ubiquitylation of the ID complex. Thus, the mono-ubiquitylated ID
      complex recruits the downstream repair protein FAN1 and facilitates the repair of
      DNA interstrand cross-links.

PMID- 20671158
TI  - Archaeology. Copper mine threatens ancient monastery in Afghanistan.

PMID- 20671157
TI  - Reframing science standards.

PMID- 20671159
TI  - 2011 budget. NSF funding request faring well in Congress.

PMID- 20671160
TI  - High energy physics. Fermilab physicists don't see Higgs, argue they should keep
      looking.

PMID- 20671161
TI  - Volcanology. Is China's riskiest volcano stirring or merely biding its time?

PMID- 20671163
TI  - International conference. Money woes cast shadow over HIV/AIDS, but ray of light
      in South Africa.

PMID- 20671165
TI  - Is pharma running out of brainy ideas?

PMID- 20671166
TI  - Ecology. Europe tries to save its eels.

PMID- 20671167
TI  - Exploration. Making smarter, savvier robots.

PMID- 20671168
TI  - Graduate education: the future is now.

PMID- 20671169
TI  - Immigration law jeopardizes university collaboration.

PMID- 20671170
TI  - Studies support probable long-term safety of MRI.

PMID- 20671171
TI  - Comment on "Patterns of diversity in marine phytoplankton".
AB  - Barton et al. (Reports, 19 March 2010, p. 1509) argued that stable conditions
      enable neutral coexistence of many phytoplankton species in the tropical oceans,
      whereas seasonal variation causes low biodiversity in subpolar oceans. However,
      their model prediction is not robust. A minor deviation from the neutrality
      assumption favors coexistence in fluctuating rather than stable environments.

PMID- 20671172
TI  - Sustainability: a household word.

PMID- 20671173
TI  - Health-care policy. To reform U.S. health care, start with systematic reviews.

PMID- 20671174
TI  - Genomics. E. coli, what a noisy bug.

PMID- 20671175
TI  - Planetary science. Winds of change on Titan.

PMID- 20671176
TI  - Reconstructing the lung.

PMID- 20671177
TI  - Chemistry. Connecting biomass and petroleum processing with a chemical bridge.

PMID- 20671178
TI  - Physics. An atomic view of quantum phase transitions.

PMID- 20671179
TI  - SPORE series winner. MIT OpenCourseWare: unlocking knowledge, empowering minds.

PMID- 20671180
TI  - New opportunities for an ancient material.
AB  - Spiders and silkworms generate silk protein fibers that embody strength and
      beauty. Orb webs are fascinating feats of bioengineering in nature, displaying
      magnificent architectures while providing essential survival utility for spiders.
      The unusual combination of high strength and extensibility is a characteristic
      unavailable to date in synthetic materials yet is attained in nature with a
      relatively simple protein processed from water. This biological template suggests
      new directions to emulate in the pursuit of new high-performance, multifunctional
      materials generated with a green chemistry and processing approach. These bio
      inspired and high-technology materials can lead to multifunctional material
      platforms that integrate with living systems for medical materials and a host of
      other applications.

PMID- 20671181
TI  - Dopaminergic network differences in human impulsivity.
AB  - Dopamine (DA) has long been implicated in impulsivity, but the precise mechanisms
      linking human variability in DA signaling to differences in impulsive traits
      remain largely unknown. By using a dual-scan positron emission tomography
      approach in healthy human volunteers with amphetamine and the D2/D3 ligand
      [18F]fallypride, we found that higher levels of trait impulsivity were predicted
      by diminished midbrain D2/D3 autoreceptor binding and greater amphetamine-induced
      DA release in the striatum, which was in turn associated with stimulant craving.
      Path analysis confirmed that the impact of decreased midbrain D2/D3 autoreceptor
      availability on trait impulsivity is mediated in part through its effect on
      stimulated striatal DA release.

PMID- 20671183
TI  - Strain-induced pseudo-magnetic fields greater than 300 tesla in graphene
      nanobubbles.
AB  - Recent theoretical proposals suggest that strain can be used to engineer graphene
      electronic states through the creation of a pseudo-magnetic field. This effect is
      unique to graphene because of its massless Dirac fermion-like band structure and
      particular lattice symmetry (C3v). Here, we present experimental spectroscopic
      measurements by scanning tunneling microscopy of highly strained nanobubbles that
      form when graphene is grown on a platinum (111) surface. The nanobubbles exhibit
      Landau levels that form in the presence of strain-induced pseudo-magnetic fields
      greater than 300 tesla. This demonstration of enormous pseudo-magnetic fields
      opens the door to both the study of charge carriers in previously inaccessible
      high magnetic field regimes and deliberate mechanical control over electronic
      structure in graphene or so-called "strain engineering."

PMID- 20671182
TI  - Quantifying E. coli proteome and transcriptome with single-molecule sensitivity
      in single cells.
AB  - Protein and messenger RNA (mRNA) copy numbers vary from cell to cell in isogenic
      bacterial populations. However, these molecules often exist in low copy numbers
      and are difficult to detect in single cells. We carried out quantitative system
      wide analyses of protein and mRNA expression in individual cells with single
      molecule sensitivity using a newly constructed yellow fluorescent protein fusion
      library for Escherichia coli. We found that almost all protein number
      distributions can be described by the gamma distribution with two fitting
      parameters which, at low expression levels, have clear physical interpretations
      as the transcription rate and protein burst size. At high expression levels, the
      distributions are dominated by extrinsic noise. We found that a single cell's
      protein and mRNA copy numbers for any given gene are uncorrelated.

PMID- 20671184
TI  - Ultrathin PbS sheets by two-dimensional oriented attachment.
AB  - Controlling anisotropy is a key concept in the generation of complex
      functionality in advanced materials. For this concept, oriented attachment of
      nanocrystal building blocks, a self-assembly of particles into larger single
      crystalline objects, is one of the most promising approaches in nanotechnology.
      We report here the two-dimensional oriented attachment of lead sulfide (PbS)
      nanocrystals into ultrathin single-crystal sheets with dimensions on the
      micrometer scale. We found that this process is initiated by cosolvents, which
      alter nucleation and growth rates during the primary nanocrystal formation, and
      is finally driven by dense packing of oleic acid ligands on {100} facets of PbS.
      The obtained nanosheets can be readily integrated in a photodetector device
      without further treatment.

PMID- 20671185
TI  - Steric effects in the chemisorption of vibrationally excited methane on Ni(100).
AB  - Newly available, powerful infrared laser sources enable the preparation of
      intense molecular beams of quantum-state prepared and aligned molecules for
      gas/surface reaction dynamics experiments. We present a stereodynamics study of
      the chemisorption of vibrationally excited methane on the (100) surface of
      nickel. Using linearly polarized infrared excitation of the C-H stretch modes of
      two methane isotopologues [CH4(nu3) and CD3H(nu1)], we aligned methane's angular
      momentum and vibrational transition dipole moment in the laboratory frame. An
      increase in methane reactivity of as much as 60% is observed when the laser
      polarization is parallel rather than normal to the surface. The dependence of the
      alignment effect on the rotational branch used for excitation indicates that
      alignment of the vibrational transition dipole moment of methane is responsible
      for the steric effect. Potential explanations for the steric effect in terms of
      an alignment-dependent reaction barrier height or electronically nonadiabatic
      effects are discussed.

PMID- 20671186
TI  - Microbial biosynthesis of alkanes.
AB  - Alkanes, the major constituents of gasoline, diesel, and jet fuel, are naturally
      produced by diverse species; however, the genetics and biochemistry behind this
      biology have remained elusive. Here we describe the discovery of an alkane
      biosynthesis pathway from cyanobacteria. The pathway consists of an acyl-acyl
      carrier protein reductase and an aldehyde decarbonylase, which together convert
      intermediates of fatty acid metabolism to alkanes and alkenes. The aldehyde
      decarbonylase is related to the broadly functional nonheme diiron enzymes.
      Heterologous expression of the alkane operon in Escherichia coli leads to the
      production and secretion of C13 to C17 mixtures of alkanes and alkenes. These
      genes and enzymes can now be leveraged for the simple and direct conversion of
      renewable raw materials to fungible hydrocarbon fuels.

PMID- 20671187
TI  - Btbd7 regulates epithelial cell dynamics and branching morphogenesis.
AB  - During embryonic development, many organs form by extensive branching of
      epithelia through the formation of clefts and buds. In cleft formation, buds are
      delineated by the conversion of epithelial cell-cell adhesions to cell-matrix
      adhesions, but the mechanisms of cleft formation are not clear. We have
      identified Btbd7 as a dynamic regulator of branching morphogenesis. Btbd7
      provides a mechanistic link between the extracellular matrix and cleft
      propagation through its highly focal expression leading to local regulation of
      Snail2 (Slug), E-cadherin, and epithelial cell motility. Inhibition experiments
      show that Btbd7 is required for branching of embryonic mammalian salivary glands
      and lungs. Hence, Btbd7 is a regulatory gene that promotes epithelial tissue
      remodeling and formation of branched organs.

PMID- 20671188
TI  - Early chordate origins of the vertebrate second heart field.
AB  - The vertebrate heart is formed from diverse embryonic territories, including the
      first and second heart fields. The second heart field (SHF) gives rise to the
      right ventricle and outflow tract, yet its evolutionary origins are unclear. We
      found that heart progenitor cells of the simple chordate Ciona intestinalis also
      generate precursors of the atrial siphon muscles (ASMs). These precursors express
      Islet and Tbx1/10, evocative of the splanchnic mesoderm that produces the lower
      jaw muscles and SHF of vertebrates. Evidence is presented that the transcription
      factor COE is a critical determinant of ASM fate. We propose that the last common
      ancestor of tunicates and vertebrates possessed multipotent cardiopharyngeal
      muscle precursors, and that their reallocation might have contributed to the
      emergence of the SHF.

PMID- 20671189
TI  - Identification of a cell of origin for human prostate cancer.
AB  - Luminal cells are believed to be the cells of origin for human prostate cancer,
      because the disease is characterized by luminal cell expansion and the absence of
      basal cells. Yet functional studies addressing the origin of human prostate
      cancer have not previously been reported because of a lack of relevant in vivo
      human models. Here we show that basal cells from primary benign human prostate
      tissue can initiate prostate cancer in immunodeficient mice. The cooperative
      effects of AKT, ERG, and androgen receptor in basal cells recapitulated the
      histological and molecular features of human prostate cancer, with loss of basal
      cells and expansion of luminal cells expressing prostate-specific antigen and
      alpha-methylacyl-CoA racemase. Our results demonstrate that histological
      characterization of cancers does not necessarily correlate with the cellular
      origins of the disease.

PMID- 20671191
TI  - Characterization of a functional C-terminus of the Mycobacterium tuberculosis
      MtrA responsible for both DNA binding and interaction with its two-component
      partner protein, MtrB.
AB  - Virulence in pathogenic bacteria is due in part to the action of two-component
      systems. However, in the human pathogen Mycobacterium tuberculosis, the molecular
      mechanisms underlying these systems are as yet unclear. In this study, MtrA was
      shown to contain a functional C-terminus and also to have Ca(2+) as its preferred
      cofactor for DNA binding. Further mutation experiments demonstrated that the C
      terminus of MtrA was responsible for specific interactions with the target DNA
      motif and also with its partner protein, MtrB. The physical interaction between
      MtrA and MtrB inhibited DNA binding by MtrA. These findings yield critical
      information about the unique regulatory mechanisms of the essential MtrAB two
      component system in this pathogen.

PMID- 20671192
TI  - FK506 causes cellular and functional defects in human natural killer cells.
AB  - The role of NK cells in allogeneic HCT has been increasingly appreciated,
      particularly in the GVL effect. Although FK506 has been used widely to prevent
      GVHD, its action was considered to be primarily through activated T cells. In
      this study, we provide direct evidence for the first time that human NK cells are
      immediate targets of FK506. Our in vivo data from patients undergoing peripheral
      blood stem cell transplantation or BMT showed a reduced number of NK cells with
      down-regulated CD25 expression in their peripheral blood compartment. Likewise,
      FK506 caused profound inhibition of NK cell proliferation in vitro and suppressed
      NK cytotoxicity and cytokine secretion in response to IL-2. These defects were
      accompanied by impaired cell clustering and selective down-regulation of adhesion
      molecules, ICAM-1, CD2, CD49d, and CD58. Furthermore, FK506 specifically
      inhibited expression of NKG2D, CD48, and DNAM1 receptors without affecting that
      of 2B4, NKp30, NKp44, and NKp46. As a result, natural cytotoxicity against K562
      tumor targets was impaired, while leaving redirected ADCC via 2B4 intact.
      Finally, FK506-treated NK cells showed impaired IL-2R signaling and inhibition of
      STAT3. Collectively, these signaling impairments and selective down-regulation of
      NK receptors by FK506 may underlie the proliferative and functional defects of NK
      cells. Thus, our data provide a new insight into the mechanism of
      immunosuppression by FK506, which should be considered to interpret the outcome
      of graft transplantation.

PMID- 20671193
TI  - Tauroursodeoxycholic acid reduces endoplasmic reticulum stress, trypsin
      activation, and acinar cell apoptosis while increasing secretion in rat
      pancreatic acini.
AB  - Endoplasmic reticulum (ER) stress leads to accumulation of un- or misfolded
      proteins inside the ER and initiates the unfolded protein response (UPR). Several
      UPR components are physiologically involved in pancreatic development and are
      pathophysiologically activated during acute pancreatitis. However, the exact role
      of ER stress in exocrine pancreatic acini is mainly unclear. The present study
      examined the effects of tauroursodeoxycholic acid (TUDCA), a known ER chaperone,
      on acinar function and UPR components. Isolated rat pancreatic acini were
      stimulated by increasing concentrations of cholecystokinin (CCK-8) with or
      without preincubation of TUDCA. UPR components were analyzed, including chaperone
      binding protein (BiP), protein kinase-like ER kinase (PERK), X-box binding
      protein (XBP)-1, c-Jun NH(2)-terminal kinase (JNK), CCAAT/enhancer binding
      protein homologues protein (CHOP), caspase 3 activation, and apoptosis. In
      addition, TUDCA effects were measured on amylase secretion, calcium signaling,
      trypsin, and cathepsin B activation. TUDCA preincubation led to a significant
      increase in amylase secretion after CCK-8 stimulation, a 50% reduction of
      intracellular trypsin activation, and reduced cathepsin B activity, although the
      effects for cathepsin B were not statistical significant. Furthermore, TUDCA
      prevented the CCK-8-induced BiP upregulation, diminished PERK and JNK
      phosphorylation, and prohibited the expression of CHOP, caspase 3 activation and
      apoptosis. XBP-1 splicing was not altered. ER stress response mechanisms are
      activated in pancreatic inflammation. Chemical chaperones enhance enzyme
      secretion of pancreatic acini, reduce ER stress responses, and attenuate ER
      stress-associated apoptosis. These data hint new perspectives for an employment
      of chemical chaperones in the therapy of acute pancreatitis.

PMID- 20671194
TI  - Transcriptional inhibition of intestinal NHE8 expression by glucocorticoids
      involves Pax5.
AB  - Sodium/hydrogen exchangers (NHEs) are a family of proteins that transport sodium
      ions into the cells by moving protons out of the cells. They play a major role in
      sodium absorption, cell volume regulation, and intracellular pH regulation. Three
      out of nine identified NHEs (NHE2, NHE3, and NHE8) are expressed on the apical
      membrane of intestinal epithelial cells. Glucocorticoids have been found to
      regulate NHE3 function in the intestine, but it is unknown if they have a similar
      function on NHE8 expression. Interestingly, high glucocorticoid levels in the
      intestine coincide chronologically with the change from high expression of NHE8
      to high expression of NHE3. Studies were performed to explore the role of
      glucocorticoids on NHE8 expression during intestinal maturation. Brush-border
      membrane vesicles were isolated from intestinal epithelia, and Western blotting
      was performed to determine NHE8 protein expression of suckling male rats treated
      with methylpredisolone. Real-time PCR was used to quantitate NHE8 mRNA expression
      in rats and Caco-2 cells. Human NHE8 promoter activity was characterized through
      transfection of Caco-2 cells. Gel mobility shift assays (GMSAs) were used to
      identify the promoter sequences and the transcription factors involved in
      glucocorticoid-mediated regulation. Our results showed that the expression of
      NHE8 mRNA and protein was decreased in glucocorticoid-treated rats and human
      intestinal epithelial cells (Caco-2). The activity of the human NHE8 gene
      promoter transfected in Caco-2 cells was also reduced by glucocorticoid
      treatment. GMSAs suggested that the reduction in promoter activity in the
      presence of glucocorticoids was due to enhanced transcription factor Pax5 binding
      on the NHE8 proximal promoter region. In conclusion, this study showed that
      glucocorticoids inhibit NHE8 gene expression by increasing Pax5 binding on NHE8
      gene promoter, suggesting an important role for Pax5 during intestinal
      maturation.

PMID- 20671195
TI  - Intestine-specific transcription factor Cdx2 induces E-cadherin function by
      enhancing the trafficking of E-cadherin to the cell membrane.
AB  - Cdx2 is an intestine-specific transcription factor required for normal intestinal
      epithelium development. Cdx2 regulates the expression of intestine-specific genes
      and induces cell adhesion and columnar morphogenesis. Cdx2 also has tumor
      suppressor properties, including the reduction of colon cancer cell proliferation
      and cell invasion, the latter due to its effects on cell adhesion. E-cadherin is
      a cell adhesion protein required for adherens junction formation and the
      establishment of intestinal cell polarity. The objective of this study was to
      elucidate the mechanism by which Cdx2 regulates E-cadherin function. Two colon
      cancer cell lines were identified in which Cdx2 expression was associated with
      increased cell-cell adhesion and diminished cell migration. In both cell lines,
      Cdx2 did not directly alter E-cadherin levels but increased its trafficking to
      the cell membrane compartment. Cdx2 enhanced this trafficking by altering
      receptor tyrosine kinase (RTK) activity. Cdx2 expression diminished
      phosphorylated Abl and phosphorylated Rac levels, which are downstream effectors
      of RTKs. Specific chemical inhibition or short interfering RNA (shRNA) knockdown
      of c-Abl kinase phenocopied Cdx2's cell-cell adhesion effects. In Colo 205 cells,
      Cdx2 reduced PDGF receptor and IGF-I receptor activation. This was mediated by
      caveolin-1, which was induced by Cdx2. Targeted shRNA knockdown of caveolin-1
      restored PDGF receptor and reversed E-cadherin membrane trafficking, despite Cdx2
      expression. We conclude that Cdx2 regulates E-cadherin function indirectly by
      disrupting RTK activity and enhancing E-cadherin trafficking to the cell membrane
      compartment. This novel mechanism advances Cdx2's prodifferentiation and
      antitumor properties and suggests that Cdx2 may broadly regulate RTK activity in
      normal intestinal epithelium by modulating membrane trafficking of proteins.

PMID- 20671196
TI  - The probiotic Lactobacillus plantarum counteracts TNF-{alpha}-induced
      downregulation of SMCT1 expression and function.
AB  - The major short-chain fatty acid (SCFA) butyrate is produced in the colonic lumen
      by bacterial fermentation of dietary fiber. Butyrate serves as primary fuel for
      the colonocytes and also ameliorates mucosal inflammation. Disturbed energy
      homeostasis seen in inflamed mucosa of inflammatory bowel disease patients has
      been attributed to impaired absorption of butyrate. Since sodium-coupled
      monocarboxylate transporter 1 (SMCT1, SLC5A8) has recently been shown to play a
      role in Na(+)-coupled transport of monocarboxylates, including SCFA, such as
      luminal butyrate, we examined the effects of proinflammatory TNF-alpha on SMCT1
      expression and function and potential anti-inflammatory role of probiotic
      Lactobacillus species in counteracting the TNF-alpha effects. Rat intestinal
      epithelial cell (IEC)-6 or human intestinal Caco-2 cells were treated with TNF
      alpha in the presence or absence of Lactobacilli culture supernatants (CS). TNF
      alpha treatments for 24 h dose-dependently inhibited SMCT1-mediated, Na(+)
      dependent butyrate uptake and SMCT1 mRNA expression in IEC-6 cells and SMCT1
      promoter activity in Caco-2 cells. CS of L. plantarum (LP) stimulated Na(+)
      dependent butyrate uptake (2.5-fold, P < 0.05), SMCT1 mRNA expression, and
      promoter activity. Furthermore, preincubating the cells with LP-CS followed by
      coincubation with TNF-alpha significantly attenuated the inhibitory effects of
      TNF-alpha on SMCT1 function, expression, and promoter activity. In vivo, oral
      administration of live LP enhanced SMCT1 mRNA expression in the colonic and ileal
      tissues of C57BL/6 mice after 24 h. Efficacy of LP or their secreted soluble
      factors to stimulate SMCT1 expression and function and to counteract the
      inhibitory effects of TNF-alpha on butyrate absorption could have potential
      therapeutic value.

PMID- 20671198
TI  - Cancer immunotherapy: in vivo imaging of adoptively transferred T cells in an
      immunocompetent host.

PMID- 20671197
TI  - Transcriptional regulation of CXC-ELR chemokines KC and MIP-2 in mouse pancreatic
      acini.
AB  - Neutrophils and their chemoattractants, the CXC-ELR chemokines keratinocyte
      cytokine (KC) and macrophage inflammatory protein-2 (MIP-2), play a critical role
      in pancreatitis. While acute pancreatitis is initiated in acinar cells, it is
      unclear if these are a source of CXC-ELR chemokines. KC and MIP-2 have NF-kappaB,
      activator protein-1 (AP-1) sites in their promoter regions. However, previous
      studies have shown increased basal and reduced caerulein-induced AP-1 activation
      in harvested pancreatic tissue in vitro, which limits interpreting the caerulein
      induced response. Moreover, recent studies suggest that NF-kappaB silencing in
      acinar cells alone may not be sufficient to reduce inflammation in acute
      pancreatitis. Thus the aim of this study was to determine whether acinar cells
      are a source of KC and MIP-2 and to understand their transcriptional regulation.
      Primary overnight-cultured murine pancreatic acini were used after confirming
      their ability to replicate physiological and pathological acinar cell responses.
      Upstream signaling resulting in KC, MIP-2 upregulation was studied along with
      activation of the transcription factors NF-kappaB and AP-1. Cultured acini
      replicated critical responses to physiological and pathological caerulein
      concentrations. KC and MIP-2 mRNA levels increased in response to supramaximal
      but not to physiological caerulein doses. This upregulation was calcium and
      protein kinase C (PKC), but not cAMP, dependent. NF-kappaB inhibition completely
      prevented upregulation of KC but not MIP-2. Complete suppression of MIP-2
      upregulation required dual inhibition of NF-kappaB and AP-1. Acinar cells are a
      likely source of KC and MIP-2 upregulation during pancreatitis. This upregulation
      is dependent on calcium and PKC. MIP-2 upregulation requires both NF-kappaB and
      AP-1 in these cells. Thus dual inhibition of NF-kappaB and AP-1 may be a more
      successful strategy to reduce inflammation in pancreatitis than targeting NF
      kappaB alone.

PMID- 20671199
TI  - Unlocking communication with the nose.

PMID- 20671200
TI  - Genome-wide identification of cis-regulatory motifs and modules underlying gene
      coregulation using statistics and phylogeny.
AB  - Cell fate determination depends in part on the establishment of specific
      transcriptional programs of gene expression. These programs result from the
      interpretation of the genomic cis-regulatory information by sequence-specific
      factors. Decoding this information in sequenced genomes is an important issue.
      Here, we developed statistical analysis tools to computationally identify the cis
      regulatory elements that control gene expression in a set of coregulated genes.
      Starting with a small number of validated and/or predicted cis-regulatory modules
      (CRMs) in a reference species as a training set, but with no a priori knowledge
      of the factors acting in trans, we computationally predicted transcription factor
      binding sites (TFBSs) and genomic CRMs underlying coregulation. This method was
      applied to the gene expression program active in Drosophila melanogaster sensory
      organ precursor cells (SOPs), a specific type of neural progenitor cells.
      Mutational analysis showed that four, including one newly characterized, out of
      the five top-ranked families of predicted TFBSs were required for SOP-specific
      gene expression. Additionaly, 19 out of the 29 top-ranked predicted CRMs directed
      gene expression in neural progenitor cells, i.e., SOPs or larval brain
      neuroblasts, with a notable fraction active in SOPs (11/29). We further
      identified the lola gene as the target of two SOP-specific CRMs and found that
      the lola gene contributed to SOP specification. The statistics and phylogeny
      based tools described here can be more generally applied to identify the cis
      regulatory elements of specific gene regulatory networks in any family of related
      species with sequenced genomes.

PMID- 20671201
TI  - Reversing the size-dependence of surface plasmon resonances.
AB  - The size-dependence of surface plasmon resonances (SPRs) is poorly understood in
      the small particle limit due to complex physical/chemical effects and
      uncertainties in experimental samples. In this article, we report an approach for
      synthesizing an ideal class of colloidal Ag nanoparticles with highly uniform
      morphologies and narrow size distributions. Optical measurements and theoretical
      analyses for particle diameters in the d approximately 2-20 nm range are
      presented. The SPR absorption band exhibits an exceptional behavior: As size
      decreases from d approximately 20 nm it blue-shifts but then turns over near d
      approximately 12 nm and strongly red-shifts. A multilayer Mie theory model agrees
      well with the observations, indicating that lowered electron conductivity in the
      outermost atomic layer, due to chemical interactions, is the cause of the red
      shift. We corroborate this picture by experimentally demonstrating precise
      chemical control of the SPR peak positions via ligand exchange.

PMID- 20671202
TI  - Adaptive multiscale model for simulating cardiac conduction.
AB  - We present a multiscale model and an adaptive numerical scheme for simulating
      cardiac action potential propagation along a linear strand of heart muscle cells.
      This model couples macroscale partial differential equations posed over the
      tissue to microscale equations posed over discrete cellular geometry. The
      microscopic equations are used only near action potential wave fronts, and the
      macroscopic equations are used everywhere else. We study the effects of gap
      junctional and ephaptic coupling on conduction in the multiscale model and its
      fully macroscale and fully microscale analogues. Our simulations reveal that the
      adaptive multiscale model accurately reproduces the action potential wave forms
      and wave speeds of the fully microscale model. They also demonstrate that, at low
      gap-junctional conductivities, the accuracy of fully macroscale simulations is
      sensitive to numerical grid spacing. Moreover, adaptive multiscale simulations
      capture the effect of ephaptic coupling, whereas fully macroscale simulations do
      not. We propose two ways of generalizing our multiscale model to higher
      dimensions, and we argue that such generalizations may be necessary to obtain
      accurate three-dimensional simulations of cardiac conduction in certain
      pathophysiological parameter regimes.

PMID- 20671203
TI  - Varietas: a functional variation database portal.
AB  - Current high-throughput technologies for investigating genomic variation in large
      population based samples produce data on a scale of millions of variations.
      Browsing through these results and identifying relevant functional variations is
      a major hurdle in these genome-wide association studies. In order to help
      researchers locate the most promising associations, we have developed a web-based
      database portal called Varietas. Varietas can be used for retrieving information
      concerning genomic variations such as single-nucleotide polymorphisms (SNPs),
      copy number variants and insertions/deletions, while enabling users to annotate
      large number of variations in a batch like manner and to find information about
      related genes, phenotypes and diseases. Varietas also links out to various
      external genomic databases, allowing users to quickly browse through a set of
      variations and follow the most promising leads. Varietas periodically integrates
      data from the major SNP and genome databases, including Ensembl genome database,
      NCBI dbSNP database, The Genomic Association Database and SNPedia. Database URL:
      http://kokki.uku.fi/bioinformatics/varietas/

PMID- 20671204
TI  - The systematic annotation of the three main GPCR families in Reactome.
AB  - Reactome is an open-source, freely available database of human biological
      pathways and processes. A major goal of our work is to provide an integrated view
      of cellular signalling processes that spans from ligand-receptor interactions to
      molecular readouts at the level of metabolic and transcriptional events. To this
      end, we have built the first catalogue of all human G protein-coupled receptors
      (GPCRs) known to bind endogenous or natural ligands. The UniProt database has
      records for 797 proteins classified as GPCRs and sorted into families A/1, B/2
      and C/3 on the basis of amino acid sequence. To these records we have added
      details from the IUPHAR database and our own manual curation of relevant
      literature to create reactions in which 563 GPCRs bind ligands and also interact
      with specific G-proteins to initiate signalling cascades. We believe the
      remaining 234 GPCRs are true orphans. The Reactome GPCR pathway can be viewed as
      a detailed interactive diagram and can be exported in many forms. It provides a
      template for the orthology-based inference of GPCR reactions for diverse model
      organism species, and can be overlaid with protein-protein interaction and gene
      expression datasets to facilitate overrepresentation studies and other forms of
      pathway analysis. Database URL: http://www.reactome.org.

PMID- 20671205
TI  - Oral and systemic health correlates of HIV-1 shedding in saliva.
AB  - The relationship among oral and systemic health and HIV shedding in saliva is not
      well-understood. We hypothesized that oral and systemic health are associated
      with HIV shedding in saliva of HIV-infected women. Saliva from 127 participants
      enrolled in the Women's Interagency HIV Study (WIHS) was collected at repeated
      visits over a 51/2-year study period (October 1998 through March 2004) and was
      evaluated for HIV-1 RNA. Demographic, lifestyle, and systemic and oral health
      characteristics were evaluated as possible correlates of salivary HIV-1 shedding.
      Multivariate models showed significantly increased risk of HIV-1 shedding in
      saliva as blood levels of CD4 cell counts decreased (p < 0.0001) and HIV RNA
      increased (p < 0.0001). Diabetes (p = 0.002) and a high proportion of gingival
      bleeding sites (p = 0.01) were associated with increased likelihood, while anti
      retroviral therapy (p = 0.0003) and higher levels of stimulated saliva flow rates
      (p = 0.02) were associated with a lower likelihood of HIV-1 RNA shedding in
      saliva.

PMID- 20671206
TI  - A randomized trial on root caries prevention in elders.
AB  - Root caries is common in institutionalized elders, and effective prevention
      methods are needed. This clinical trial compared the effectiveness of four
      methods in preventing new root caries. From 21 residential homes, 306 generally
      healthy elders having at least 5 teeth with exposed sound root surfaces were
      randomly allocated into one of four groups: (1) individualized oral hygiene
      instruction (OHI); (2) OHI and applications of 1% chlorhexidine varnish every 3
      months; (3) OHI and applications of 5% sodium fluoride varnish every 3 months;
      and (4) OHI and annual applications of 38% silver diamine fluoride (SDF)
      solution. Two-thirds (203/306) of the elders were followed for 3 years. Mean
      numbers of new root caries surfaces in the four groups were 2.5, 1.1, 0.9, and
      0.7, respectively (ANOVA, p < 0.001). SDF solution, sodium fluoride varnish, and
      chlorhexidine varnish were more effective in preventing new root caries than
      giving OHI alone.

PMID- 20671207
TI  - What makes a tumor diagnosis a call to action? On the preference for action
      versus inaction.
AB  - BACKGROUND: Many studies have shown an omission bias, but when the context is
      cancer, people seem to prefer active treatments to watchful waiting. OBJECTIVE:
      First, to investigate whether the preference for active treatment for cancer
      could depend on the associations attached to the inaction option, and second, to
      explore the kind of diagnosis that gives rise to the preference for action, by
      comparing scenarios differing in the status of the illness (already present v.
      could arise in the future), the kind of diagnosis (malign tumor, benign tumor, or
      nontumor), and the possible development of the tumor (growth v. degeneration).
      DESIGN: Between-subjects design with 8 hypothetical scenarios. PARTICIPANTS: A
      total of 735 students participated in an Internet survey. MEASUREMENTS: Choice
      between watchful waiting and surgery, perceived severity of the diagnosis.
      RESULTS: Active treatment was preferred only when the scenario described watchful
      waiting as excluding surgery in the future. The critical aspect for participants'
      preference for active treatment was the malignancy of the tumor currently
      diagnosed. Perceived severity was also a significant predictor of treatment
      choice. LIMITATIONS: Inability to infer causation in the relationship between
      choice and perceived severity. CONCLUSIONS: Action is preferred to inaction when
      a malignant tumor is currently diagnosed and active treatments are not allowed in
      the future; under other conditions, participants prefer inaction (e.g., when
      active treatments are allowed in the future, or when the tumor is benign) or
      exhibit no preference (e.g., when it is not specified whether active treatments
      are allowed in the future).

PMID- 20671208
TI  - Are medical outcomes fungible? A survey of voters, medical administrators, and
      physicians.
AB  - PURPOSE: Many analyses of medical treatments entail the aggregation of health
      outcomes over patients and over time. This study assessed the extent to which
      voters, medical administrators, and physicians consider such aggregation to be
      appropriate. In addition, the study assessed whether this perceived fungibility
      of outcomes moderates the difference between treatment recommendations in single
      play decisions (for 1 patient on 1 occasion) and those in repeated-play decisions
      (for several patients or for 1 patient on several occasions). METHODS: In a 5
      contact mail survey of registered voters (n = 182, response rate = 52%), medical
      administrators (n = 123, 35%), and physicians (n = 95, 26%), respondents rated
      the fungibility of outcomes and indicated their preferred action in 1 of 3
      scenarios involving changes in life expectancy or the duration of pain. They
      evaluated a risky, positive-expected-value treatment in a single-play decision,
      then in a repeated-play decision, and again in a repeated-play decision after
      they viewed the distribution of possible net outcomes. RESULTS: Perceived
      fungibility varied substantially across respondents in all groups, with voters
      giving higher fungibility ratings than administrators or physicians. Respondents'
      strength-of-preference ratings for treatment increased from single-play to
      repeated-play decisions, but these increases were moderated by perceived
      fungibility, as expected. When outcomes were considered fungible, treatments were
      much more attractive in repeated-play decisions than in single-play decisions.
      When outcomes were considered nonfungible, there was essentially no difference
      between single- and repeated-play decisions. CONCLUSIONS: Recommendations
      regarding risky medical treatments with positive expectations appear to depend,
      in part, on opinions about whether it is reasonable to aggregate medical outcomes
      over patients or over time. Such opinions vary widely among physicians and
      others.

PMID- 20671209
TI  - Effect of arrangement of stick figures on estimates of proportion in risk
      graphics.
AB  - BACKGROUND: Health risks are sometimes illustrated with stick figures, with a
      certain proportion colored to indicate they are affected by the disease.
      Perception of these graphics may be affected by whether the affected stick
      figures are scattered randomly throughout the group or arranged in a block.
      OBJECTIVE: . To assess the effects of stick-figure arrangement on first
      impressions of estimates of proportion, under a 10-s deadline. DESIGN: .
      Questionnaire. Participants and Setting. Respondents recruited online (n = 100)
      or in waiting rooms at an urban hospital (n = 65). Intervention. Participants
      were asked to estimate the proportion represented in 6 unlabeled graphics, half
      randomly arranged and half sequentially arranged. Measurements. Estimated
      proportions. RESULTS: . Although average estimates were fairly good, the
      variability of estimates was high. Overestimates of random graphics were larger
      than overestimates of sequential ones, except when the proportion was near 50%;
      variability was also higher with random graphics. Although the average inaccuracy
      was modest, it was large enough that more than one quarter of respondents
      confused 2 graphics depicting proportions that differed by 11 percentage points.
      Low numeracy and educational level were associated with inaccuracy. Limitations.
      Participants estimated proportions but did not report perceived risk.
      CONCLUSIONS: . Randomly arranged arrays of stick figures should be used with care
      because viewers' ability to estimate the proportion in these graphics is so poor
      that moderate differences between risks may not be visible. In addition, random
      arrangements may create an initial impression that proportions, especially large
      ones, are larger than they are.

PMID- 20671210
TI  - The effect of health state selection on the valuation of EQ-5D.
AB  - BACKGROUND: Many aspects of valuation STUDY DESIGN: s are poorly understood, and
      the size and composition of health states used in valuation studies vary widely.
      Our aims were to investigate the impact of the selection of a subset of EQ-5D
      health states in generating a set of visual analog scale (VAS)-based values. Our
      aims were to investigate the optimal number of health states, the sample size
      required per health state, and which combinations of health states are required
      to establish a EQ-5D VAS value set. METHODS: Data were drawn from a United
      Kingdom (UK) general population postal survey in which all health states defined
      by EQ-5D were evaluated using VAS. We used a simulation approach to address each
      question, and the performance of each estimation model was assessed by the
      average value of the mean absolute errors. RESULTS: Despite the constraint of the
      small sample size in the study dataset, the results suggest that the optimal
      number of states for a valuation study is 32, 100 observations per health state
      were sufficient, and multiple subsets of health states were feasible.
      CONCLUSIONS: Selecting health states not included in the "Measurement and
      Valuation of Health" dataset in valuation studies is quite specifically
      encouraged. However, it remains prudent to ensure that the selection of health
      states covers as wide a range of severity as possible. Setting the number of
      observations per health state to 150 might allow for correction of any errors in
      data collection or processing. The extent to which the results of this study
      based on VAS valuation data can be safely generalized to the design of time
      tradeoff valuation studies remains an open question.

PMID- 20671211
TI  - Communication of uncertainty regarding individualized cancer risk estimates:
      effects and influential factors.
AB  - OBJECTIVE: To examine the effects of communicating uncertainty regarding
      individualized colorectal cancer risk estimates and to identify factors that
      influence these effects. METHODS: Two Web-based experiments were conducted, in
      which adults aged 40 years and older were provided with hypothetical
      individualized colorectal cancer risk estimates differing in the extent and
      representation of expressed uncertainty. The uncertainty consisted of imprecision
      (otherwise known as "ambiguity") of the risk estimates and was communicated using
      different representations of confidence intervals. Experiment 1 (n = 240) tested
      the effects of ambiguity (confidence interval v. point estimate) and
      representational format (textual v. visual) on cancer risk perceptions and worry.
      Potential effect modifiers, including personality type (optimism), numeracy, and
      the information's perceived credibility, were examined, along with the influence
      of communicating uncertainty on responses to comparative risk information.
      Experiment 2 (n = 135) tested enhanced representations of ambiguity that
      incorporated supplemental textual and visual depictions. RESULTS: Communicating
      uncertainty led to heightened cancer-related worry in participants, exemplifying
      the phenomenon of "ambiguity aversion." This effect was moderated by
      representational format and dispositional optimism; textual (v. visual) format
      and low (v. high) optimism were associated with greater ambiguity aversion.
      However, when enhanced representations were used to communicate uncertainty,
      textual and visual formats showed similar effects. Both the communication of
      uncertainty and use of the visual format diminished the influence of comparative
      risk information on risk perceptions. CONCLUSIONS: The communication of
      uncertainty regarding cancer risk estimates has complex effects, which include
      heightening cancer-related worry-consistent with ambiguity aversion-and
      diminishing the influence of comparative risk information on risk perceptions.
      These responses are influenced by representational format and personality type,
      and the influence of format appears to be modifiable and content dependent.

PMID- 20671212
TI  - Health effects in significant others: separating family and care-giving effects.
AB  - BACKGROUND: Changes in the health of patients may affect the health of so-called
      "significant others" in 2 distinct ways. First, an individual may provide
      informal care to the patient and be burdened by the process of care giving. We
      label this indirect effect of a patient's health on the health of the care giver
      the "care-giving effect." Second, a person may suffer from health losses because
      someone in his or her social environment is ill, regardless of his or her care
      giving status. The health of the patient then directly affects the health of this
      significant other, which we label the "family effect." METHODS: We investigate
      the occurrence of the family and care-giving effect in a convenience sample of
      Dutch care givers (n = 751). The family effect was approximated by the health
      status of the patient (measured on EuroQol-VAS), and the care-giving effect by
      the number of the care-giving tasks was provided. It was assumed that care
      givers' health is positively associated with patients' health, that is, the
      family effect, and negatively associated with care-giving burden, that is, the
      care-giving effect. Relationships are studied using multivariate regressions.
      RESULTS: Our results support the existence of both types of health effects. The
      analysis shows that the 2 effects are separable and independently associated with
      the health of care givers. Not accounting for the family effect conflates the
      care-giving effect. CONCLUSIONS: If the goal of health care policy is to optimize
      health, all important effects should be captured. The scope of economic
      evaluations should also include health effects in significant others. This study
      suggests that significant others include both care givers and broader groups of
      affected individuals, such as family members.

PMID- 20671213
TI  - Graph literacy: a cross-cultural comparison.
AB  - BACKGROUND: Visual displays are often used to communicate important medical
      information to patients. However, even the simplest graphs are not understood by
      everyone. OBJECTIVE: To develop and test a scale to measure health-related graph
      literacy and investigate the level of graph literacy in the United States and
      Germany. DESIGN: Experimental and questionnaire studies. Setting. Computerized
      studies in the laboratory and on probabilistic national samples in the United
      States and Germany. Participants. Nationally representative samples of people 25
      to 69 years of age in Germany (n = 495) and the United States (n = 492).
      Laboratory pretest on 60 younger and 60 older people. Measurements. Psychometric
      properties of the scale (i.e., reliability, validity, discriminability) and level
      of graph literacy in the two countries. RESULTS: The new graph literacy scale
      predicted which patients can benefit from visual aids and had promising
      measurement properties. Participants in both countries completed approximately 9
      of 13 items correctly (in Germany, x- = 9.4, s = 2.6; in the United States, x- =
      9.3, s = 2.9). Approximately one third of the population in both countries had
      both low graph literacy and low numeracy skills. Limitations. The authors focused
      on basic graph literacy only. They used a computerized scale; comparability with
      paper-and-pencil versions should be checked. CONCLUSIONS: The new graph literacy
      scale seems to be a suitable tool for assessing whether patients understand
      common graphical formats and shows that not everyone profits from standard visual
      displays. Research is needed on communication formats that can overcome the
      barriers of both low numeracy and graph literacy.

PMID- 20671214
TI  - Albuminuria and estimated glomerular filtration rate independently associate with
      acute kidney injury.
AB  - Acute kidney injury (AKI) is increasingly common and a significant contributor to
      excess death in hospitalized patients. CKD is an established risk factor for AKI;
      however, the independent graded association of urine albumin excretion with AKI
      is unknown. We analyzed a prospective cohort of 11,200 participants in the
      Atherosclerosis Risk in Communities (ARIC) study for the association between
      baseline urine albumin-to-creatinine ratio and estimated GFR (eGFR) with
      hospitalizations or death with AKI. The incidence of AKI events was 4.0 per 1000
      person-years of follow-up. Using participants with urine albumin-to-creatinine
      ratios <10 mg/g as a reference, the relative hazards of AKI, adjusted for age,
      gender, race, cardiovascular risk factors, and categories of eGFR were 1.9 (95%
      CI, 1.4 to 2.6), 2.2 (95% CI, 1.6 to 3.0), and 4.8 (95% CI, 3.2 to 7.2) for urine
      albumin-to-creatinine ratio groups of 11 to 29 mg/g, 30 to 299 mg/g, and >=300
      mg/g, respectively. Similarly, the overall adjusted relative hazard of AKI
      increased with decreasing eGFR. Patterns persisted within subgroups of age, race,
      and gender. In summary, albuminuria and eGFR have strong, independent
      associations with incident AKI.

PMID- 20671215
TI  - Low health literacy associates with increased mortality in ESRD.
AB  - Limited health literacy is common in the United States and associates with poor
      clinical outcomes. Little is known about the effect of health literacy in
      patients with advanced kidney disease. In this prospective cohort study we
      describe the prevalence of limited health literacy and examine its association
      with the risk for mortality in hemodialysis patients. We enrolled 480 incident
      chronic hemodialysis patients from 77 dialysis clinics between 2005 and 2007 and
      followed them until April 2008. Measured using the Rapid Estimate of Adult
      Literacy in Medicine, 32% of patients had limited (<9th grade reading level) and
      68% had adequate health literacy (>=9th grade reading level). Limited health
      literacy was more likely in patients who were male and non-white and who had
      fewer years of education. Compared with adequate literacy, limited health
      literacy associated with a higher risk for death (HR 1.54; 95% CI 1.01 to 2.36)
      even after adjustment for age, sex, race, and diabetes. In summary, limited
      health literacy is common and associates with higher mortality in chronic
      hemodialysis patients. Addressing health literacy may improve survival for these
      patients.

PMID- 20671216
TI  - A maladaptive role for EP4 receptors in podocytes.
AB  - Inhibition of p38 mitogen-activated protein kinase and cyclooxygenase-2 reduces
      albuminuria in models of chronic kidney disease marked by podocyte injury.
      Previously, we identified a feedback loop in podocytes whereby an in vitro
      surrogate for glomerular capillary pressure (i.e., mechanical stretch) along with
      prostaglandin E(2) stimulation of its EP4 receptor induced cyclooxygenase-2 in a
      p38-dependent manner. Here we asked whether stimulation of EP4 receptors would
      exacerbate glomerulopathies associated with enhanced glomerular capillary
      pressure. We generated mice with either podocyte-specific overexpression or
      depletion of the EP4 receptor (EP4(pod+) and EP4(pod-/-), respectively).
      Glomerular prostaglandin E(2)-stimulated cAMP levels were eightfold greater for
      EP4(pod+) mice compared with nontransgenic (non-TG) mice. In contrast, EP4 mRNA
      levels were >50% lower, and prostaglandin E(2)-induced cAMP synthesis was absent
      in podocytes isolated from EP4(pod-/-) mice. Non-TG and EP4(pod+) mice underwent
      5/6 nephrectomy and exhibited similar increases in systolic BP (+25 mmHg) by 4
      weeks compared with sham-operated controls. Two weeks after nephrectomy, the
      albumin-creatinine ratio of EP4(pod+) mice (3438 MUg/mg) was significantly higher
      than that of non-TG mice (773 MUg/mg; P < 0.0001). Consistent with more severe
      renal injury, the survival rate for nephrectomized EP4(pod+) mice was
      significantly lower than that for non-TG mice (14 versus 67%). In contrast, 6
      weeks after nephrectomy, the albumin-creatinine ratio of EP4(pod-/-) mice (753
      MUg/mg) was significantly lower than that of non-TG mice (2516 MUg/mg; P < 0.05).
      These findings suggest that prostaglandin E(2), acting via EP4 receptors
      contributes to podocyte injury and compromises the glomerular filtration barrier.

PMID- 20671217
TI  - Glycemic control and extended hemodialysis survival in patients with diabetes
      mellitus: comparative results of traditional and time-dependent Cox model
      analyses.
AB  - BACKGROUND AND OBJECTIVES: The benefits and risks of aggressive glycemic control
      in diabetes mellitus complicated by end-stage kidney failure remain uncertain but
      have importance because of the large patient population with inferior overall
      prognosis. Recent large observational studies with differing methodologies
      reached somewhat contrasting conclusions regarding the association of hemoglobin
      A1c with survival in diabetic chronic hemodialysis patients. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: This study supplements the authors' previous
      analysis (which found no correlation) by extending the follow-up period to 3
      years and using time-dependent survival models with repeated measures. Among
      24,875 nationally distributed study patients, 94.5% had type 2 diabetes, allowing
      additional analysis in the subset with type 1 diabetes. Data were collected at
      baseline and every quarter to a maximum of 3 years' follow-up. RESULTS: Adjusted
      standard and time-dependent Cox models indicated that only extremes of glycemia
      were associated with inferior survival. There was no effect modification by serum
      albumin levels, a marker of protein nutrition status, and no trend associated
      with random glucose measurements in a post hoc analysis. In type 1 diabetic
      patients, upper extreme hemoglobin A1c values indicated lower survival risk.
      CONCLUSIONS: Sustained extremes of glycemia were only variably and weakly
      associated with decreased survival in this population. In the absence of
      randomized, controlled trials, these results suggest that aggressive glycemic
      control cannot be routinely recommended for all diabetic hemodialysis patients on
      the basis of reducing mortality risk. Physicians are encouraged to individualize
      glycemic targets based on potential risks and benefits in diabetic ESRD patients.

PMID- 20671218
TI  - Patient and technique survival among a Canadian multicenter nocturnal home
      hemodialysis cohort.
AB  - BACKGROUND AND OBJECTIVES: As a result of improved clinical and quality-of-life
      outcomes compared with conventional hemodialysis, interest in nocturnal home
      hemodialysis (NHD) has steadily increased in the past decade; however, little is
      known about the flow of patients through NHD programs or about patient-specific
      predictors of mortality or technique failure associated with this modality. This
      study addressed this gap in knowledge. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: This study included 247 NHD patients of the Canadian Slow Long
      nightly ExtEnded dialysis Programs (CAN-SLEEP) cohort from 1994 through 2006
      inclusive. The association between program- and patient-specific variables and
      risk for adverse outcomes was determined using uni- and multivariable Cox
      regression. RESULTS: A total of 14.6% of the cohort experienced death or
      technique failure. Unadjusted 1- and 5-year adverse event-free survival was 95.2
      and 80.1%, respectively. Significant predictors of a composite of mortality and
      technique failure included advanced age (P < 0.001), diabetes (P < 0.001),
      central venous catheter use (P = 0.01), and inability to perform NHD
      independently (P = 0.009) and were adjusted for center effect. Weekly frequency
      of NHD was not predictive. Age and diabetes remained significant with
      multivariable analysis (hazard ratio 1.07 and 2.64, respectively). Unadjusted 1-
      and 5-year technique survival was 97.9 and 95.2%, respectively. Only age was a
      significant predictor of technique failure. CONCLUSIONS: NHD is associated with
      excellent adverse event-free survival. This study underscores the importance of
      modality-specific predictors in the success of home hemodialysis, as well as
      favorable baseline characteristics such as younger age and the absence of
      diabetes.

PMID- 20671219
TI  - Hemoglobin A1c in hemodialysis patients: should one size fit all?

PMID- 20671220
TI  - Renal transplantation in patients with sarcoidosis: a French multicenter study.
AB  - BACKGROUND AND OBJECTIVES: Sarcoidosis is a multisystem disorder of unknown
      etiology. The outcome of renal transplantation on patients with sarcoidosis is
      not well known. A few case reports have described recurrence of sarcoidosis after
      transplant. Here, we report for the first time results and outcome of renal
      transplantation in a series of patients with sarcoidosis. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: Eighteen patients with sarcoidosis who underwent
      renal transplantation were identified retrospectively in eight French renal
      transplantation departments. Patient medical charts, demographics, and the
      outcome of renal transplantation were reviewed. RESULTS: Initial renal disease
      was related to sarcoidosis in 10 patients. At the end of the follow-up (median,
      42 months), patient and death-censored graft survival were 94.4% and the mean GFR
      was 60 ml/min per 1.73 m(2). Five patients (27%) experienced recurrence of
      sarcoidosis including extra-renal involvement in two patients and renal
      involvement in three patients. Median GFR was lower in the group of patients with
      renal recurrence compared with that of the entire cohort: 31 ml/min per 1.73
      m(2). Recurrence occurred shortly after transplantation (median period, 13
      months). Risk factors for recurrence included primary renal disease related to
      sarcoidosis and a shorter delay between the last episode of sarcoidosis and renal
      transplantation. CONCLUSIONS: Our results indicate that renal transplantation may
      be carried out safely in transplant candidates with sarcoidosis. Recurrence is
      not rare and is likely to affect graft outcome. These results fully justify a
      specific clinical and histologic monitoring mainly during the early
      posttransplant period.

PMID- 20671221
TI  - Determining optimum hemoglobin sampling for anemia management from every
      treatment data.
AB  - BACKGROUND AND OBJECTIVES: Anemia management protocols in ESRD call for
      hemoglobin (Hb) monitoring every 2 to 4 weeks. Short-term Hb variability affects
      the reliability of Hb measurement and may lead to incorrect dosing of
      erythropoiesis stimulating agents. We prospectively analyzed short-term Hb
      variability and quantified the relationship between frequency of Hb monitoring
      and error in Hb estimation. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using
      the Crit-Line III TQA device, we prospectively observed Hb during each dialysis
      treatment in 49 ESRD patients and quantified long- and short-term Hb variability.
      We estimated Hb from data sampled at regular intervals; 8*, 4*, 2*, or 1* per
      month to establish how well we account for short-term variability at different
      monitoring intervals. We calculated the Hb estimation error (Hb(err)) as a root
      mean-squared difference between the observed and estimated Hb and compared it
      with the measurement error. RESULTS: The most accurate Hb estimation is achieved
      when monitoring 8* per month (Hb(err) = 0.23 +/- 0.05 g/dl), but it exceeds the
      accuracy of the measurement device. The estimation error increases to 0.34 +/-
      0.07 g/dl when monitoring 4* per month, 0.39 +/- 0.08 g/dl when monitoring 2* a
      month, and 0.45 +/- 0.09 g/dl when monitoring 1* per month. Estimation error
      comparable to instrument error information is as follows: 8* per month, 15
      patients; 4* per month, 22 patients; 2* per month, 6 patients; 1* per a month, 6
      patients. CONCLUSIONS: Four times a month is the clinically optimal Hb monitoring
      frequency for anemia management.

PMID- 20671222
TI  - Off-pump coronary artery bypass surgery and acute kidney injury: a meta-analysis
      of randomized controlled trials.
AB  - BACKGROUND AND OBJECTIVES: Off-pump coronary artery bypass grafting (CABG) has
      been advocated to cause less inflammation, morbidity, and mortality than the more
      traditional on-pump technique. This meta-analysis compares these two surgical
      techniques with respect to causing acute kidney injury (AKI). DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: This study searched for randomized controlled
      trials in MEDLINE and abstracts from the proceedings of scientific meetings
      through February 2010. Included were trials comparing off-pump to on-pump CABG
      that reported the incidence of AKI, as defined by a mixture of criteria including
      biochemical parameter/urine output/dialysis requirement. Mortality was evaluated
      among the studies that reported kidney-related outcomes. For primary and subgroup
      analyses, fixed-effect meta-analyses of odds ratios (OR) were performed. RESULTS:
      In 22 identified trials (4819 patients), the weighted incidence of AKI in the on
      pump CABG group was 4.0% (95% confidence interval [CI] 1.8%, 8.5%), dialysis
      requirement 2.4% (95% CI 1.6%, 3.7%), and mortality 2.6% (95% CI 1.6%, 4.0%). By
      meta-analysis, off-pump CABG was associated with a 40% lower odds of
      postoperative AKI (OR 0.60; 95% CI 0.43, 0.84; P = 0.003) and a nonsignificant
      33% lower odds for dialysis requirement (OR 0.67; 95% CI 0.40, 1.12; P = 0.12).
      Within the selected trials, off-pump CABG was not associated with a significant
      decrease in mortality. CONCLUSIONS: Off-pump CABG may be associated with a lower
      incidence of postoperative AKI but may not affect dialysis requirement, a serious
      complication of cardiac surgery. However, the different definitions of AKI used
      in individual trials and methodological concerns preclude definitive conclusions.

PMID- 20671223
TI  - Rituximab treatment for vasculitis.

PMID- 20671224
TI  - Urinary expression of kidney injury markers in renal transplant recipients.
AB  - BACKGROUND AND OBJECTIVES: The outcome of renal transplantation after an episode
      of acute rejection is difficult to predict, even with an allograft biopsy. We
      examined whether urinary expression of specific biomarker mRNA could be used as a
      noninvasive prognostic marker in kidney transplant recipients. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: We studied 63 kidney transplant recipients who
      require graft biopsy because of progressive worsening of kidney function. The
      mRNA of neutrophil gelatinase-associated lipocalin, kidney injury molecule-1 (KIM
      1), IL-18, surfactant protein-C, and S100 calcium-binding proteins A8 and A9 in
      urinary sediment were quantified. RESULTS: Urinary expressions of neutrophil
      gelatinase-associated lipocalin, KIM-1, and IL-18, but not other target genes,
      were significantly different between histologic groups (P < 0.0001 for all).
      After followed for an average of 39.7 +/- 21.1 months, the rate of renal function
      decline significantly correlated with urinary KIM-1 expression (r = -0.434, P =
      0.0004) but not other target genes. At 48 months, the graft survival rate for the
      high and low KIM-1 groups were 46.2 and 78.6%, respectively. After adjusting for
      confounding variables, each log of higher urinary KIM-1 expression conferred an
      ~2.9-fold higher risk of developing graft failure (95% confidence interval, 1.3-
      to 6.2-fold; P = 0.006). The result remained similar when only patients with no
      acute cellular rejection were analyzed. CONCLUSIONS: In kidney allograft
      recipients, urinary KIM-1 expression provides prognostic information in relation
      to the rate of renal function decline, irrespective of the kidney pathology.

PMID- 20671225
TI  - Effects of add-on fluvastatin therapy in patients with chronic proteinuric
      nephropathy on dual renin-angiotensin system blockade: the ESPLANADE trial.
AB  - BACKGROUND AND OBJECTIVES: This open, prospective, randomized trial aimed to
      assess the effects of statins in chronic kidney disease patients on optimized
      antiproteinuric treatment with combined angiotensin-converting enzyme inhibition
      and angiotensin receptor blockade. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:
      After 1-month benazepril therapy followed by 1-month benazepril-valsartan
      combined therapy (run-in), 186 consenting patients with residual proteinuria >0.5
      g/24 h were randomized to 6-month benazepril-valsartan therapy alone or combined
      with fluvastatin. Between-groups changes in proteinuria (primary outcome), serum
      lipids, and GFR were compared by ANCOVA. Analyses were blinded and by intention
      to treat. RESULTS: During the run-in, proteinuria decreased more on benazepril
      valsartan than on benazepril alone. Proteinuria reduction correlated with
      concomitant reduction in total, LDL, and HDL cholesterol, and apolipoprotein B
      and apolipoprotein A levels. After randomization, median proteinuria similarly
      decreased from 1.2 (0.6 to 2.2) to 1.1 (0.5 to 1.7) g/24 h on fluvastatin and
      from 1.5 (0.8 to 2.7) to 1.0 (0.5 to 2.4) g/24 h on benazapril-valsartan therapy
      alone. Fluvastatin further reduced total and LDL cholesterol and apolipoprotein B
      versus benazepril-valsartan alone, but did not affect serum triglycerides and
      GFR. Treatment was well tolerated. CONCLUSIONS: In chronic kidney disease
      patients with residual proteinuria despite combined angiotensin-converting enzyme
      inhibitor and angiotensin receptor blockade therapy, add-on fluvastatin does not
      affect urinary proteins, but further reduces serum lipids and is safe. Whether
      combined angiotensin-converting enzyme inhibitor, angiotensin receptor blockade,
      and statin therapy may improve cardiovascular outcomes in this high-risk
      population is worth investigating.

PMID- 20671226
TI  - Characteristics of acute kidney injury in patients infected with the 2009
      influenza A (H1N1) virus.
AB  - BACKGROUND AND OBJECTIVES: There have been few studies investigating acute kidney
      injury (AKI) in patients infected with the 2009 pandemic influenza A (H1N1)
      virus. Therefore, the objective of this study was to identify the factors
      associated with AKI in H1N1-infected patients. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: This was a study of 47 consecutive critically ill adult patients
      with reverse transcriptase-PCR-confirmed H1N1 infection in Brazil. Outcome
      measures were AKI (as defined by the Risk, Injury, Failure, Loss, and End-stage
      renal failure [RIFLE] criteria) and in-hospital death. RESULTS: AKI was
      identified in 25 (53%) of the 47 H1N1-infected patients. AKI was associated with
      vasopressor use, mechanical ventilation, high Acute Physiology and Chronic Health
      Evaluation II (APACHE II) scores, and severe acidosis as well as with higher
      levels of C-reactive protein and lactic dehydrogenase upon intensive care unit
      (ICU) admission. A nephrology consultation was requested for 16 patients (64%),
      and 8 (50%) required dialysis. At ICU admission, 7 (15%) of the 25 AKI patients
      had not yet progressed to AKI. However, by 72 hours after ICU admission, no
      difference in RIFLE score was found between AKI survivors and nonsurvivors. Of
      the 47 patients, 9 (19%) died, all with AKI. Mortality was associated with
      mechanical ventilation, vasopressor use, dialysis, high APACHE II score, high
      bilirubin levels, and a low RIFLE score at ICU admission. CONCLUSIONS: Among
      critically ill H1N1-infected patients, the incidence of AKI is high. In such
      patients, AKI is mainly attributable to shock.

PMID- 20671227
TI  - Improved prognosis in patients with autosomal dominant polycystic kidney disease
      in Denmark.
AB  - BACKGROUND AND OBJECTIVES: The introduction of new therapies, including agents
      that block the renin-angiotensin system, may have affected progression of
      autosomal dominant polycystic kidney disease (ADPKD). We investigated whether the
      age when reaching ESRD and survival during renal replacement therapy in Danish
      patients with ADPKD changed from January 1, 1990, through December 31, 2007.
      DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: According to the Danish National
      Registry on Regular Dialysis and Transplantation, 693 patients with ADPKD reached
      ESRD in the study period. The 18 years were divided into three consecutive 6-year
      intervals. RESULTS: The incidence of reaching ESRD for patients with ADPKD
      increased from 6.45 per million people in 1990 through 1995 to 7.59 per million
      people in 2002 through 2007, and the mean age at onset of ESRD increased by 4.7
      years. The age-adjusted male-to-female ratio for onset of ESRD changed from 1.6
      to 1.1, indicating a trend toward similar progression in both genders. From onset
      of ESRD, a Cox regression analysis to compare the first and second 6-year
      intervals, adjusted for age, gender, and treatment modality, showed that patient
      survival improved by 38%. Although NS, a similar trend was found during the
      second and third time intervals. CONCLUSIONS: This study demonstrates that in
      Danish patients with ADPKD, the prognosis had significantly improved during the
      study period. Furthermore, the results indicate that male gender may be losing
      its importance as a risk factor for progression in ADPKD.

PMID- 20671228
TI  - Synergistic induction of mitogen-activated protein kinase phosphatase-1 by
      thrombin and epidermal growth factor requires vascular endothelial growth factor
      receptor-2.
AB  - OBJECTIVE: To determine the molecular mechanism underlying the synergistic
      response of mitogen-activated protein kinase phosphatase-1 (MKP-1), which is
      induced by thrombin and epidermal growth factor (EGF). METHODS AND RESULTS: MKP-1
      induction by thrombin (approximately 6-fold) was synergistically increased
      (approximately 18-fold) by cotreatment with EGF in cultured endothelial cells.
      EGF alone did not induce MKP-1 substantially (<2-fold). The synergistic induction
      of MKP-1 was not mediated by matrix metalloproteinases. The EGF receptor kinase
      inhibitor AG1478 blocked approximately 70% of MKP-1 induction by thrombin plus
      EGF (from 18- to 6-fold) but not the response to thrombin alone. An extracellular
      signal-regulated kinase (ERK)-dependent protease-activated receptor-1 (PAR-1)
      signal was required for the thrombin alone effect; an ERK-independent PAR-1
      signal was necessary for the approximately 12-fold MKP-1 induction by thrombin
      plus EGF. VEGF induction of MKP-1 was also approximately 12-fold and c-Jun N
      terminal kinase (JNK) dependent. Inhibitors of extracellular signal-regulated
      kinase and JNK activation blocked thrombin plus EGF-induced MKP-1 completely.
      Furthermore, VEGF receptor 2 depletion blocked the synergistic response without
      affecting the induction of MKP-1 by thrombin alone. CONCLUSIONS: We have
      identified a novel signaling interaction between protease-activated receptor-1
      and EGF receptor that is mediated by VEGF receptor 2 and results in synergistic
      MKP-1 induction.

PMID- 20671229
TI  - Ets-1 and Ets-2 regulate the expression of microRNA-126 in endothelial cells.
AB  - OBJECTIVE: MicroRNA plays important roles in vascular biology, but the regulation
      of endothelial-specific microRNA is not well characterized. MicroRNA-126 (miR
      126) is highly expressed in endothelial cells, and it regulates angiogenesis and
      vascular inflammation. Here we show that the transcription factors Ets-1 and Ets
      2 regulate miR-126 expression. METHODS AND RESULTS: A genomic region between -71
      and -100 bp upstream of the miR-126 transcriptional start site is critical for
      transactivation of the gene containing miR-126. This genomic region contains a
      potential Ets binding site. Mutations within the Ets binding site block
      transactivation, and Ets-1 and Ets-2 interact with this critical genomic region.
      Knockdown of endogenous Ets-1 and Ets-2 decreases miR-126 expression. Finally,
      knockdown of miR-126 alters regulation of an Ets-1 target gene. CONCLUSIONS:
      Taken together, these data show that the transcription factors Ets-1 and Ets-2
      play a key role in controlling the expression of miR-126 and suggest that miR-126
      may mediate some of their vascular effects.

PMID- 20671230
TI  - Smooth muscle cell-specific insulin-like growth factor-1 overexpression in Apoe-/
      mice does not alter atherosclerotic plaque burden but increases features of
      plaque stability.
AB  - OBJECTIVE: Growth factors may play a permissive role in atherosclerosis
      initiation and progression, in part via their promotion of vascular smooth muscle
      cell (VSMC) accumulation in plaques. However, unstable human plaques often have a
      relative paucity of VSMC, which has been suggested to contribute to plaque
      rupture and erosion and to clinical events. Insulin-like growth factor-1 (IGF-1)
      is an endocrine and autocrine/paracrine growth factor that is a mitogen for VSMC,
      but when infused into Apoe(-/-) mice it paradoxically reduces atherosclerosis
      burden. METHODS AND RESULTS: To determine the effect of stimulation of VSMC
      growth on atherosclerotic plaque development and to understand mechanisms of IGF
      1's atheroprotective effect, we assessed atherosclerotic plaques in mice
      overexpressing IGF-1 in smooth muscle cells (SMC) under the control of the alpha
      smooth muscle actin promoter, after backcrossing to the Apoe(-/-) background
      (SMP8/Apoe(-/-)). Compared with Apoe(-/-) mice, these SMP8/Apoe(-/-) mice
      developed a comparable plaque burden after 12 weeks on a Western diet, suggesting
      that the ability of increased circulating IGF-1 to reduce plaque burden was
      mediated in large part via non-SMC target cells. However, advanced plaques in
      SMP8/Apoe(-/-) mice displayed several features of plaque stability, including
      increased fibrous cap area, alpha-smooth muscle actin-positive SMC and collagen
      content, and reduced necrotic cores. CONCLUSIONS: These findings indicate that
      stimulation of VSMC IGF-1 signaling does not alter total atherosclerotic plaque
      burden and may improve atherosclerotic plaque stability.

PMID- 20671231
TI  - Plasma gamma-glutamyltransferase, cysteinyl-glycine, and oxidized low-density
      lipoprotein: a pathway associated with myocardial infarction risk?
AB  - OBJECTIVE: To investigate the interrelation between plasma gamma
      glutamyltransferase (GGT) activity, cysteinyl-glycine (Cys-Gly) (ie, a thiol
      originating from GGT-mediated cleavage of glutathione), and oxidized low-density
      lipoprotein (oxLDL) with regard to myocardial infarction (MI) risk in a
      prospective study. METHODS AND RESULTS: Incident cases of MI were identified
      among European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam
      participants without prior MI during 6.0 years of follow-up. Baseline levels of
      Cys-Gly and oxLDL and GGT activity in plasma were measured in a case-cohort study
      comprising 837 subjects without incident MI and 116 subjects with incident MI.
      The relation of GGT, Cys-Gly and oxLDL to MI risk was assessed using Cox
      proportional hazards regression analysis. After adjustment for established risk
      factors, hazard ratios associated with a 1-SD unit increase in the log
      transformed biomarker were 1.63 (95% CI, 1.30 to 2.05) for GGT, 1.36 (95% CI,
      1.07 to 1.72) for Cys-Gly, and 1.37 (95% CI, 1.00 to 1.86) for oxLDL. Cys-Gly and
      oxLDL accounted for 2.3% of the relation between GGT and MI risk. CONCLUSIONS:
      The positive association between GGT activity and MI risk appears to be
      independent of circulating Cys-Gly and oxLDL levels. With Cys-Gly, we found a
      potential new predictor of MI risk whose impact needs to be further elucidated.

PMID- 20671232
TI  - The effect of aging on venous valves.
AB  - OBJECTIVE: Age is the strongest risk factor for venous thrombosis. Vessel wall
      changes such as thickening of venous valves may be one of the contributing
      mechanisms. We determined thickness and function of venous valves in the
      popliteal vein with ultrasound in 77 healthy individuals. METHODS AND RESULTS:
      The study included 6 age groups ranging from 20 to 80 years old. Thickness of the
      valves was compared between age groups. Valve closure time was assessed as an
      indicator for valve function. In 69 of 77 participants, valve parameters could be
      measured. We found an increasing thickness of the valves with age, with a mean
      thickness of 0.35 mm (range, 0.25 to 0.44 mm) in the group of 20 to 30 years and
      0.59 mm (range, 0.30 to 1.21 mm) in the group of 71 to 80 years. The increase in
      valve thickness per year (linear regression coefficient) was 0.004 mm (95% CI, 0
      to 0.009). Valve function was not directly associated with age. Valve thickness,
      however, was inversely associated with valve function. CONCLUSIONS: Our results
      show that deep venous valves change with age, with thicker valves in older
      individuals. The increase of valve thickness with age may be part of the
      explanation for the age gradient seen in the incidence of venous thrombosis.

PMID- 20671233
TI  - Dabigatran: an oral novel potent reversible nonpeptide inhibitor of thrombin.
AB  - Dabigatran is a highly selective, reversible, and potent thrombin inhibitor and
      is orally available as the prodrug, dabigatran etexilate. It has shown
      antithrombotic efficacy in animal models of thrombosis, with a rapid onset of
      action and predictable pharmacodynamic response. Peak plasma concentrations of
      dabigatran occur 1 to 2 hours after ingestion of the prodrug. The terminal half
      life of dabigatran is 12 to 14 hours in elderly volunteers. Dabigatran is not
      metabolized by cytochrome P450 isoenzymes and does not interact with food.
      Dabigatran has a low potential for drug-drug interactions and is predominantly
      renally excreted. Dabigatran etexilate as chronic therapy effectively prevents
      the recurrence of venous thromboembolism and cardioembolic stroke. For the first
      time, it has been demonstrated clinically that there may be an effective and safe
      alternative to warfarin.

PMID- 20671234
TI  - Sphingosine-1-phosphate-dependent activation of p38 MAPK maintains elevated
      peripheral resistance in heart failure through increased myogenic
      vasoconstriction.
AB  - RATIONALE: Mechanisms underlying vasomotor abnormalities and increased peripheral
      resistance exacerbating heart failure (HF) are poorly understood. OBJECTIVE: To
      explore the role and molecular basis of myogenic responses in HF. METHODS AND
      RESULTS: 10 weeks old C57Bl6 mice underwent experimental myocardial infarction
      (MI) or sham surgery. At 1 to 12 weeks postoperative, mice underwent hemodynamic
      studies, mesenteric, cerebral, and cremaster artery perfusion myography and
      Western blot. Organ weights and hemodynamics confirmed HF and increased
      peripheral resistance after MI. Myogenic responses, ie, pressure-induced
      vasoconstriction, were increased as early as 1 week after MI and remained
      elevated. Vasoconstrictor responses to phenylephrine were decreased 1 week after
      MI, but not at 2 to 6 weeks after MI, whereas those to endothelin (ET)-1 and
      sphingosine-1-phosphate (S1P) were increased at all time points after MI. An
      antagonist (JTE-013) for the most abundant S1P receptor detected in mesenteric
      arteries (S1P(2)R) abolished the enhanced myogenic responses of HF, with
      significantly less effect on controls. Mice with genetic absence of sphingosine
      kinases or S1P(2)R (Sphk1(-/-); Sphk1(-/-)/Sphk2(+/-); S1P(2)R(-/-)) did not
      manifest enhanced myogenic responses after MI. Mesenteric arteries from HF mice
      exhibited increased phosphorylation of myosin light chain, with deactivation of
      its phosphatase (MLCP). Among known S1P-responsive regulators of MLCP, GTP-Rho
      levels were unexpectedly reduced in HF, whereas levels of activated p38 MAPK and
      ERK1/2 (extracellular signal-regulated kinase 1/2) were increased. Inhibiting p38
      MAPK abolished the myogenic responses of animals with HF, with little effect on
      controls. CONCLUSIONS: Rho-independent p38 MAPK-mediated deactivation of MLCP
      underlies S1P/S1P(2)R-regulated increases in myogenic vasoconstriction observed
      in HF. Therapeutic targeting of these findings in HF models deserves study.

PMID- 20671235
TI  - Unexpected role of the copper transporter ATP7A in PDGF-induced vascular smooth
      muscle cell migration.
AB  - RATIONALE: Copper, an essential nutrient, has been implicated in vascular
      remodeling and atherosclerosis with unknown mechanism. Bioavailability of
      intracellular copper is regulated not only by the copper importer CTR1 (copper
      transporter 1) but also by the copper exporter ATP7A (Menkes ATPase), whose
      function is achieved through copper-dependent translocation from trans-Golgi
      network (TGN). Platelet-derived growth factor (PDGF) promotes vascular smooth
      muscle cell (VSMC) migration, a key component of neointimal formation. OBJECTIVE:
      To determine the role of copper transporter ATP7A in PDGF-induced VSMC migration.
      METHODS AND RESULTS: Depletion of ATP7A inhibited VSMC migration in response to
      PDGF or wound scratch in a CTR1/copper-dependent manner. PDGF stimulation
      promoted ATP7A translocation from the TGN to lipid rafts, which localized at the
      leading edge, where it colocalized with PDGF receptor and Rac1, in migrating
      VSMCs. Mechanistically, ATP7A small interfering RNA or CTR small interfering RNA
      prevented PDGF-induced Rac1 translocation to the leading edge, thereby inhibiting
      lamellipodia formation. In addition, ATP7A depletion prevented a PDGF-induced
      decrease in copper level and secretory copper enzyme precursor prolysyl oxidase
      (Pro-LOX) in lipid raft fraction, as well as PDGF-induced increase in LOX
      activity. In vivo, ATP7A expression was markedly increased and copper
      accumulation was observed by synchrotron-based x-ray fluorescence microscopy at
      neointimal VSMCs in wire injury model. CONCLUSIONS: These findings suggest that
      ATP7A plays an important role in copper-dependent PDGF-stimulated VSMC migration
      via recruiting Rac1 to lipid rafts at the leading edge, as well as regulating LOX
      activity. This may contribute to neointimal formation after vascular injury. Our
      findings provide insight into ATP7A as a novel therapeutic target for vascular
      remodeling and atherosclerosis.

PMID- 20671236
TI  - Neuregulin/ErbB signaling regulates cardiac subtype specification in
      differentiating human embryonic stem cells.
AB  - RATIONALE: Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) exhibit
      either a "working" chamber or a nodal-like phenotype. To generate optimal hESC-CM
      preparations for eventual clinical application in cell-based therapies, we will
      need to control their differentiation into these specialized cardiac subtypes.
      OBJECTIVE: To demonstrate intact neuregulin (NRG)-1beta/ErbB signaling in hESC
      CMs and test the hypothesis that this signaling pathway regulates cardiac subtype
      abundance in hESC-CM cultures. METHODS AND RESULTS: All experiments used hESC-CM
      cultures generated using our recently reported directed differentiation protocol.
      To support subsequent action potential phenotyping approaches and provide a
      higher-throughput method of determining cardiac subtype, we first developed and
      validated a novel genetic label that identifies nodal-type hESC-CMs. Next,
      control hESC-CM preparations were compared to those differentiated in the
      presence of exogenous NRG-1beta, an anti-NRG-1beta neutralizing antibody, or the
      ErbB antagonist AG1478. We used 3 independent approaches to determine the ratio
      of cardiac subtypes in the resultant populations: direct action potential
      phenotyping under current-clamp, activation of the aforementioned genetic label,
      and subtype-specific marker expression by RT-PCR. Using all 3 end points, we
      found that inhibition of NRG-1beta/ErbB signaling greatly enhanced the proportion
      of cells showing the nodal phenotype. CONCLUSIONS: NRG-1beta/ErbB signaling
      regulates the ratio of nodal- to working-type cells in differentiating hESC-CM
      cultures and presumably functions similarly during early human heart development.
      We speculate that, by manipulating NRG-1beta/ErbB signaling, it will be possible
      to generate preparations of enriched working-type myocytes for infarct repair,
      or, conversely, nodal cells for potential use in a biological pacemaker.

PMID- 20671237
TI  - Developmental origin, growth, and three-dimensional architecture of the
      atrioventricular conduction axis of the mouse heart.
AB  - RATIONALE: The clinically important atrioventricular conduction axis is
      structurally complex and heterogeneous, and its molecular composition and
      developmental origin are uncertain. OBJECTIVE: To assess the molecular
      composition and 3D architecture of the atrioventricular conduction axis in the
      postnatal mouse heart and to define the developmental origin of its component
      parts. METHODS AND RESULTS: We generated an interactive 3D model of the
      atrioventricular junctions in the mouse heart using the patterns of expression of
      Tbx3, Hcn4, Cx40, Cx43, Cx45, and Nav1.5, which are important for conduction
      system function. We found extensive figure-of-eight rings of nodal and
      transitional cells around the mitral and tricuspid junctions and in the base of
      the atrial septum. The rings included the compact node and nodal extensions. We
      then used genetic lineage labeling tools (Tbx2(+/Cre), Mef2c-AHF-Cre,
      Tbx18(+/Cre)), along with morphometric analyses, to assess the developmental
      origin of the specific components of the axis. The majority of the atrial
      components, including the atrioventricular rings and compact node, are derived
      from the embryonic atrioventricular canal. The atrioventricular bundle, including
      the lower cells of the atrioventricular node, in contrast, is derived from the
      ventricular myocardium. No contributions to the conduction system myocardium were
      identified from the sinus venosus, the epicardium, or the dorsal mesenchymal
      protrusion. CONCLUSIONS: The atrioventricular conduction axis comprises multiple
      domains with distinctive molecular signatures. The atrial part proliferates from
      the embryonic atrioventricular canal, along with myocytes derived from the
      developing atrial septum. The atrioventricular bundle and lower nodal cells are
      derived from ventricular myocardium.

PMID- 20671238
TI  - Bone marrow mesenchymal stem cells stimulate cardiac stem cell proliferation and
      differentiation.
AB  - RATIONALE: The regenerative potential of the heart is insufficient to fully
      restore functioning myocardium after injury, motivating the quest for a cell
      based replacement strategy. Bone marrow-derived mesenchymal stem cells (MSCs)
      have the capacity for cardiac repair that appears to exceed their capacity for
      differentiation into cardiac myocytes. OBJECTIVE: Here, we test the hypothesis
      that bone marrow derived MSCs stimulate the proliferation and differentiation of
      endogenous cardiac stem cells (CSCs) as part of their regenerative repertoire.
      METHODS AND RESULTS: Female Yorkshire pigs (n=31) underwent experimental
      myocardial infarction (MI), and 3 days later, received transendocardial
      injections of allogeneic male bone marrow-derived MSCs, MSC concentrated
      conditioned medium (CCM), or placebo (Plasmalyte). A no-injection control group
      was also studied. MSCs engrafted and differentiated into cardiomyocytes and
      vascular structures. In addition, endogenous c-kit(+) CSCs increased 20-fold in
      MSC-treated animals versus controls (P<0.001), there was a 6-fold increase in
      GATA-4(+) CSCs in MSC versus control (P<0.001), and mitotic myocytes increased 4
      fold (P=0.005). Porcine endomyocardial biopsies were harvested and plated as
      organotypic cultures in the presence or absence of MSC feeder layers. In vitro,
      MSCs stimulated c-kit(+) CSCs proliferation into enriched populations of adult
      cardioblasts that expressed Nkx2-5 and troponin I. CONCLUSIONS: MSCs stimulate
      host CSCs, a new mechanism of action underlying successful cell-based
      therapeutics.

PMID- 20671239
TI  - Receptor activator of nuclear factor kappaB ligand is a novel inducer of tissue
      factor in macrophages.
AB  - RATIONALE: Although recent studies have suggested a role for the receptor
      activator of nuclear factor kappaB ligand (RANKL) in the late stages of
      atherosclerosis (eg, plaque destabilization and rupture), the underlying
      mechanisms and subsequent events are unclear. OBJECTIVE: Because blood clotting
      is common after plaque rupture, we hypothesized that RANKL influenced tissue
      factor (TF) expression and activity to initiate the coagulation cascade. METHODS
      AND RESULTS: RANKL increased the TF mRNA level and procoagulant activity in
      macrophages, as determined by semiquantitative reverse transcription polymerase
      chain reaction (semiquantitative RT-PCR) and a chromogenic assay. TF promoter
      analysis revealed that AP-1 and Egr-1 are responsible for RANKL-induced TF
      transcription. In addition, RANKL increased phosphorylation of c-Jun NH(2)
      terminal kinase (JNK) and extracellular signal-regulated kinase (ERK)1/2. RANKL
      induced TF expression was attenuated by JNK- and MEK1-specific inhibitors and by
      small interfering RNA knockdown of c-Jun and Egr-1. CONCLUSION: Our results
      indicate that RANKL induces TF in macrophages mainly through the cooperative
      action of AP-1 and Egr-1 via JNK and ERK1/2 pathways. These findings provide
      strong mechanistic support for the role of RANKL in the thrombogenicity of
      atherosclerotic plaques.

PMID- 20671240
TI  - Genetic Ace2 deficiency accentuates vascular inflammation and atherosclerosis in
      the ApoE knockout mouse.
AB  - RATIONALE: Angiotensin-converting enzyme (ACE)2 opposes the actions of
      angiotensin (Ang) II by degrading it to Ang 1-7. OBJECTIVE: Given the important
      role of Ang II/Ang 1-7 in atherogenesis, we investigated the impact of ACE2
      deficiency on the development of atherosclerosis. METHODS AND RESULTS: C57Bl6,
      Ace2 knockout (KO), apolipoprotein E (ApoE) KO and ApoE/Ace2 double KO mice were
      followed until 30 weeks of age. Plaque accumulation was increased in ApoE/Ace2
      double KO mice when compared to ApoE KO mice. This was associated with increased
      expression of adhesion molecules and inflammatory cytokines, including
      interleukin-6, monocyte chemoattractant protein-1, and vascular cell adhesion
      molecule-1, and an early increase in white cell adhesion across the whole aortae
      on dynamic flow assay. In the absence of a proatherosclerotic (ApoE KO) genotype,
      ACE2 deficiency was also associated with increased expression of these markers,
      suggesting that these differences were not an epiphenomenon. ACE inhibition
      prevented increases of these markers and atherogenesis in ApoE/ACE2 double KO
      mice. Bone marrow macrophages isolated from Ace2 KO mice showed increased
      proinflammatory responsiveness to lipopolysaccharide and Ang II when compared to
      macrophages isolated from C57Bl6 mice. Endothelial cells isolated from Ace2 KO
      mice also showed increased basal activation and elevated inflammatory
      responsiveness to TNF-alpha. Similarly, selective inhibition of ACE2 with MLN
      4760 also resulted in a proinflammatory phenotype with a physiological response
      similar to that observed with exogenous Ang II (10(-7) mol/L). CONCLUSIONS:
      Genetic Ace2 deficiency is associated with upregulation of putative mediators of
      atherogenesis and enhances responsiveness to proinflammatory stimuli. In
      atherosclerosis-prone ApoE KO mice, these changes potentially contribute to
      increased plaque accumulation. These findings emphasize the potential utility of
      ACE2 repletion as a strategy to reduce atherosclerosis.

PMID- 20671241
TI  - Increasing cardiac contractility after myocardial infarction exacerbates cardiac
      injury and pump dysfunction.
AB  - RATIONALE: Myocardial infarction (MI) leads to heart failure (HF) and premature
      death. The respective roles of myocyte death and depressed myocyte contractility
      in the induction of HF after MI have not been clearly defined and are the focus
      of this study. OBJECTIVES: We developed a mouse model in which we could prevent
      depressed myocyte contractility after MI and used it to test the idea that
      preventing depression of myocyte Ca(2+)-handling defects could avert post-MI
      cardiac pump dysfunction. METHODS AND RESULTS: MI was produced in mice with
      inducible, cardiac-specific expression of the beta2a subunit of the L-type Ca(2+)
      channel. Myocyte and cardiac function were compared in control and beta2a animals
      before and after MI. beta2a myocytes had increased Ca(2+) current; sarcoplasmic
      reticulum Ca(2+) load, contraction and Ca(2+) transients (versus controls), and
      beta2a hearts had increased performance before MI. After MI, cardiac function
      decreased. However, ventricular dilation, myocyte hypertrophy and death, and
      depressed cardiac pump function were greater in beta2a versus control hearts
      after MI. beta2a animals also had poorer survival after MI. Myocytes isolated
      from beta2a hearts after MI did not develop depressed Ca(2+) handling, and Ca(2+)
      current, contractions, and Ca(2+) transients were still above control levels
      (before MI). CONCLUSIONS: Maintaining myocyte contractility after MI, by
      increasing Ca(2+) influx, depresses rather than improves cardiac pump function
      after MI by reducing myocyte number.

PMID- 20671242
TI  - Sympathetic stimulation of adult cardiomyocytes requires association of AKAP5
      with a subpopulation of L-type calcium channels.
AB  - RATIONALE: Sympathetic stimulation of the heart increases the force of
      contraction and rate of ventricular relaxation by triggering protein kinase (PK)A
      dependent phosphorylation of proteins that regulate intracellular calcium. We
      hypothesized that scaffolding of cAMP signaling complexes by AKAP5 is required
      for efficient sympathetic stimulation of calcium transients. OBJECTIVE: We
      examined the function of AKAP5 in the beta-adrenergic signaling cascade. METHODS
      AND RESULTS: We used calcium imaging and electrophysiology to examine the
      sympathetic response of cardiomyocytes isolated from wild type and AKAP5 mutant
      animals. The beta-adrenergic regulation of calcium transients and the
      phosphorylation of substrates involved in calcium handling were disrupted in
      AKAP5 knockout cardiomyocytes. The scaffolding protein, AKAP5 (also called
      AKAP150/79), targets adenylyl cyclase, PKA, and calcineurin to a caveolin 3
      associated complex in ventricular myocytes that also binds a unique subpopulation
      of Ca(v)1.2 L-type calcium channels. Only the caveolin 3-associated Ca(v)1.2
      channels are phosphorylated by PKA in response to sympathetic stimulation in wild
      type heart. However, in the AKAP5 knockout heart, the organization of this
      signaling complex is disrupted, adenylyl cyclase 5/6 no longer associates with
      caveolin 3 in the T-tubules, and noncaveolin 3-associated calcium channels become
      phosphorylated after beta-adrenergic stimulation, although this does not lead to
      an enhanced calcium transient. The signaling domain created by AKAP5 is also
      essential for the PKA-dependent phosphorylation of ryanodine receptors and
      phospholamban. CONCLUSIONS: These findings identify an AKAP5-organized signaling
      module that is associated with caveolin 3 and is essential for sympathetic
      stimulation of the calcium transient in adult heart cells.

PMID- 20671244
TI  - Psychometric comparisons of 3 functional ambulation measures for patients with
      stroke.
AB  - BACKGROUND AND PURPOSE: We compared the test-retest reliability, validity, and
      responsiveness of the Dynamic Gait Index, the 4-item Dynamic Gait Index, and the
      Functional Gait Assessment for assessment of walking in patients with stroke.
      METHODS: Forty-five outpatients participating in the validity and responsiveness
      study were tested using the 3 walking measures as well as the 10-m walk test,
      Barthel Index, and Postural Assessment Scale for Stroke Patients. We tested them
      during the first week, then again after 2 months and 5 months of therapy. Another
      48 chronic patients completed the 3 measures twice, 1 week apart, in the test
      retest reliability study. RESULTS: Thirty-five participants completed 3 time
      point assessments. The Functional Gait Assessment showed the least floor and
      ceiling effects, indicating it has the best discriminative ability for patients
      with stroke with high walking function. We found the 3 measures were highly
      correlated with each other, indicating excellent concurrent validity, and all
      measures at the first week of therapy were moderately to highly correlated with
      the Barthel Index scores at 5 months, indicating good predictive validity.
      Responsiveness of the 3 measures was moderate during a 5-month period, and all
      showed good test-retest reliability. The minimal detectable changes between tests
      indicate acceptable random error. CONCLUSIONS: All 3 measures showed sufficient
      validity, responsiveness, and reliability for assessment of walking function in
      patients with stroke undergoing rehabilitation, but the Functional Gait
      Assessment is recommended for its psychometric properties.

PMID- 20671243
TI  - High-mobility group box 1 promotes metalloproteinase-9 upregulation through Toll
      like receptor 4 after cerebral ischemia.
AB  - BACKGROUND AND PURPOSE: HMGB1 is a nuclear protein and an alarmin that signals
      cell damage in response to injury. It is believed that after release from injured
      cells, HMGB1 binds to its receptors to stimulate cross-talk among cells and to
      drive components of the inflammatory cascade. This study was intended to
      investigate the role of extracellular HMGB1 in ischemic stroke by examining the
      response of the zymogen matrix metalloproteinase-9 (MMP-9) to HMGB1 in vivo and
      in vitro. METHODS: Toll-like receptor 2 (TLR2), TLR4, receptor for advanced
      glycation endproducts (RAGE), and MMP-9 expression was examined using
      quantitative RT-PCR in primary cultured neurons, astrocytes, and mouse brain
      after HMGB1 addition. MMP-9 expression/activity was examined using zymography.
      Middle cerebral artery occlusion was induced for 60 minutes using a filament
      model. RESULTS: TLR4 is constitutively expressed in neurons, astrocytes, and
      mouse brain. HMGB1 addition to neuronal and glial cell cultures caused MMP-9
      upregulation in a dose- and time-dependent manner. Lack of TLR4 function
      attenuated MMP-9 expression induced by HMGB1 in vitro. After striatal
      microinjection of HMGB1, MMP-9 was upregulated, and the response was independent
      of tumor necrosis factor-alpha. Interestingly, MMP-9 upregulation was reduced in
      TLR4 missense mutant mice after ischemia compared with wild-type controls, as was
      infarct volume. CONCLUSIONS: Our results suggest that HMGB1 triggers MMP-9
      upregulation in neurons and astrocytes predominantly via TLR4 after cerebral
      ischemia. Hence, targeting HMGB1/TLRs signaling pathway may reduce the acute
      inflammatory response and reduce tissue damage in cerebral ischemia.

PMID- 20671245
TI  - Niacin treatment of stroke increases synaptic plasticity and axon growth in rats.
AB  - BACKGROUND AND PURPOSE: Niacin is the most effective medication in current
      clinical use for increasing high-density lipoprotein cholesterol. We tested the
      hypothesis that niacin treatment of stroke promotes synaptic plasticity and axon
      growth in the ischemic brain. METHODS: Male Wistar rats were subjected to 2 hours
      of middle cerebral artery occlusion and treated with or without Niaspan (a
      prolonged-release formulation of niacin, 40 mg/kg) daily for 14 days starting 24
      hours after middle cerebral artery occlusion. The expression of synaptophysin,
      Nogo receptor, Bielschowsky silver, brain-derived neurotrophic factor, and its
      receptor tropomyosin-related kinase B were measured by immunohistostaining and
      Western blot, respectively, in the ischemic brain. Complementing in vivo studies,
      primary cultured neurons were used to test the effect of niacin and high-density
      lipoprotein on neurite outgrowth and brain-derived neurotrophic
      factor/tropomyosin-related kinase B expression. RESULTS: Niaspan treatment of
      stroke significantly increased synaptophysin, Bielschowsky silver, brain-derived
      neurotrophic factor/tropomyosin-related kinase B expression, and decreased Nogo
      receptor expression in the ischemic brain compared with middle cerebral artery
      occlusion control animals (P<0.05, n=8/group). Niacin and high-density
      lipoprotein treatment significantly increased neurite outgrowth and brain-derived
      neurotrophic factor/tropomyosin-related kinase B expression in primary cultured
      neurons. Tropomyosin-related kinase B inhibitor attenuated niacin-induced neurite
      outgrowth (P<0.05, n=6/group). CONCLUSIONS: Niacin treatment of stroke promotes
      synaptic plasticity and axon growth, which is mediated, at least partially, by
      the brain-derived neurotrophic factor/tropomyosin-related kinase B pathways.

PMID- 20671246
TI  - Neuroprotective effect of Bax-inhibiting peptide on neonatal brain injury.
AB  - BACKGROUND AND PURPOSE: Mitochondria play a critical role in mediating cell death
      in both the adult and immature brain. The cyclophilin D mitochondrial membrane
      permeability transition pore is critical in adult ischemia, whereas in neonatal
      hypoxic-ischemic (HI) brain injury, mitochondrial permeabilization appears to be
      primarily Bax-dependent. The aim of this study was to evaluate the
      neuroprotective effect of a cell-penetrating Bax-inhibiting peptide (BIP) on
      neonatal mouse HI brain injury. METHODS: BIP (5 microL, 5 mg/mL) or a BIP
      negative control (5 microL, 5 mg/mL) was injected intracerebroventricularly
      immediately before HI in postnatal day 9 mice. Mice were euthanized at different
      time points after HI for evaluation of brain injury, Bax activation, release of
      proapoptotic proteins, and caspase activation. The trace fear conditioning and
      cylinder tests were performed for evaluation of the functional recovery after BIP
      treatment. RESULTS: At 5 days after HI, there was a 41.2% reduction of brain
      injury in BIP-treated mice compared with BIP-negative control treated animals.
      Myelin basic protein and neurofilament quantification revealed that BIP reduced
      white matter injury. BIP treatment conferred improvement in both sensorimotor and
      memory functions at 7 weeks after HI. BIP protection was associated with a
      reduction of Bax activation, mitochondrial permeabilization, and downstream
      caspase activation. CONCLUSIONS: Bax inhibition provides neuroprotection and
      functional improvement in a neonatal mouse model of HI.

PMID- 20671248
TI  - Evidence-based practice needs stronger prognostic scores for the prediction of
      recurrent stroke.

PMID- 20671247
TI  - Isolation of locally derived stem/progenitor cells from the peri-infarct area
      that do not migrate from the lateral ventricle after cortical stroke.
AB  - BACKGROUND AND PURPOSE: Neurogenesis can arise from neural stem/progenitor cells
      of the subventricular zone after strokes involving both the cortex and striatum.
      However, it is controversial whether all types of stroke and strokes of different
      sizes activate neurogenesis from the subventricular zone niche. In contrast with
      cortical/striatal strokes, repair and remodeling after mild cortical strokes may
      involve to a greater extent local cortical stem/progenitor cells and cells from
      nonneurogenic niches. METHODS: We compared stem/progenitor cell responses after
      focal cortical strokes produced by distal middle cerebral artery occlusion and
      cortical/striatal strokes produced by the intraluminal suture model. To label
      migrating neuroblasts from the subventricular zone, we injected DiI to the
      lateral ventricle after distal middle cerebral artery occlusion. By
      immunohistochemistry, we characterized cells expressing stem/progenitor cell
      markers in the peri-infarct area. We isolated cortical stem/progenitor cells from
      the peri-infarct area after distal middle cerebral artery occlusion and assayed
      their self-renewal and differentiation capacity. RESULTS: In contrast with
      cortical/striatal strokes, focal cortical strokes did not induce neuroblast
      migration from the subventricular zone to the infarct zone after distal middle
      cerebral artery occlusion. By immunohistochemistry, we observed subpopulations of
      reactive astrocytes in the peri-infarct area that coexpressed radial glial cell
      markers such as Sox2, Nestin, and RC2. Clonal neural spheres isolated from the
      peri-infarct area after distal middle cerebral artery occlusion differentiated
      into neurons, astrocytes, oligodendrocytes, and smooth muscle cells. Notably,
      neural spheres isolated from the peri-infarct area also expressed RC2 before
      differentiation. CONCLUSIONS: Mild cortical strokes that do not penetrate the
      striatum activate local cortical stem/progenitor cells but do not induce
      neuroblast migration from the subventricular zone niche.

PMID- 20671249
TI  - The association of the 4q25 susceptibility variant for atrial fibrillation with
      stroke is limited to stroke of cardioembolic etiology.
AB  - BACKGROUND AND PURPOSE: Genome-wide association studies recently identified 2
      variants on chromosome 4q25 as susceptibility factors for atrial fibrillation.
      Interestingly, these variants were subsequently also shown to be associated with
      stroke. However, it remains unclear whether 4q25 associates with all the stroke
      subtypes or with cardioembolic stroke in particular, which is often attributable
      to atrial fibrillation. METHODS: We performed a large case-control association
      study in 4199 ischemic stroke patients, all subtyped according to Trial of Org
      10172 in Acute Stroke Treatment criteria, and 3750 controls derived from 6
      studies conducted in Australia, Austria, Belgium, Poland, Spain, and Sweden. Two
      variants on chromosome 4q25, rs1906591 and rs10033464, were genotyped. RESULTS:
      Within cases, the A-allele of rs1906591 was associated with atrial fibrillation
      (odds ratio, 1.64 [95% CI, 1.43 to 1.90]; P=9.2 . 10(-12)), whereas rs10033464
      was only marginally associated. There was an association between overall ischemic
      stroke and rs1906591 (odds ratio, 1.20 [95% CI, 1.09 to 1.32]; P=1.2 . 10(-4)).
      However, this was probably caused by the large effect of stroke of cardioembolic
      etiology because no relation was obtained in any other subgroup of stroke. The
      rs10033464 variant failed to show any relationship with ischemic stroke.
      CONCLUSIONS: We replicated the association of the rs1906591 variant on chromosome
      4q25 with atrial fibrillation and ischemic stroke of cardioembolic etiology. The
      4q25 locus failed to associate with noncardiac subtypes of ischemic stroke.

PMID- 20671250
TI  - Cerebral small vessel disease and kidney function predict long-term survival in
      patients with acute stroke.
AB  - BACKGROUND AND PURPOSE: Cerebral small vessel disease reflected by white matter
      lesions (WMLs) in MRI and kidney function reflected by estimated glomerular
      filtration rate (eGFR) is closely associated in patients without stroke. We
      studied whether eGFR and WMLs predict long-term survival in patients with acute
      stroke. METHODS: After exclusion of patients with low eGFR (N=5 [1.3%]; <30
      mL/min/1.73 m(2)), consecutive patients with acute stroke (N=378) subjected to
      MRI and serum creatinine determination were included in the study and
      prospectively followed-up up to 12 years. RESULTS: Of the patients, 71.2% had
      died during the follow-up, 152 (40.2%) had moderate (eGFR <60 mL/min/1.73 m(2)),
      and 226 (59.8%) had normal or mildly impaired eGFR (>or=60 mL/min/1.73 m(2)). Of
      the patients, 108 (28.6%) had mild, 68 (18.0%) had moderate, and 202 (53.4%) had
      severe WMLs. In logistic regression analysis adjusted with age and sex, eGFR <60
      mL/min/1.73 m(2) was associated with severe WMLs (relative risk 2.77, 95% CI 1.10
      to 6.98, P=0.030). In Cox regression survival analysis adjusted with significant
      covariates, eGFR <60 mL/min/1.73 m(2) (1.30, 95% CI 1.00 to 1.68, P=0.047) and
      severe WMLs (hazard ratio 1.32, 95% CI 1.02 to 1.71, P=0.033) were associated
      with poor survival, whereas they were not independent from each other. In further
      analyses, presence of either eGFR >or=60 mL/min/1.73 m(2) or only mild to
      moderate WMLs, or both, was associated with improved survival compared with all
      other combinations. CONCLUSIONS: Cerebral small vessel disease is closely
      associated with kidney function in patients with acute stroke. Cerebral small
      vessel disease and kidney function are closely associated predictors of poor
      poststroke survival.

PMID- 20671251
TI  - Constructing the prediction model for the risk of stroke in a Chinese population:
      report from a cohort study in Taiwan.
AB  - BACKGROUND AND PURPOSE: Prediction rules for the risk of stroke have been
      proposed. However, most studies were conducted with whites or for secondary
      prevention, and it is not clear whether these models apply to the Chinese
      population. The purpose of this study was to construct a simple points-based
      clinical model for predicting incident stroke among Chinese adults in Taiwan.
      METHODS: We estimated the 10-year risk of stroke in a cohort study of middle-aged
      and elderly participants who were free from stroke at baseline. Multivariate Cox
      model-derived coefficients were used to construct the simple points-based
      clinical and biochemical model and the prediction measures using the area under
      the receive operating characteristic curve, net reclassification improvement, and
      integrated discrimination improvement statistics were applied. RESULTS: Of the
      3513 participants without stroke at baseline, 240 incident cases of stroke were
      documented for a median 15.9-year follow-up. Age (8 points), gender (1 point),
      systolic blood pressure (3 points), diastolic blood pressure (2 points), family
      history of stroke (1 point), atrial fibrillation (3 points), and diabetes (1
      point) were found to significantly predict stroke events. The estimated area
      under the receive operating characteristic curve for this clinical points-based
      model was 0.772 (95% CI, 0.744 to 0.799). The discrimination ability of this
      clinical model was similar to the coefficients-based models and better than
      available stroke models. CONCLUSIONS: We have constructed a model for predicting
      15-year incidence of stroke in Chinese adults and this model may be useful in
      identifying individuals at high risk of stroke.

PMID- 20671252
TI  - Erythropoietin in combination of tissue plasminogen activator exacerbates brain
      hemorrhage when treatment is initiated 6 hours after stroke.
AB  - BACKGROUND AND PURPOSE: Erythropoietin (EPO), a hematopoietic cytokine, exerts
      neuroprotective effects in experimental stroke. In the present study, we
      investigated the effect of recombinant human EPO (rhEPO) in combination with
      tissue plasminogen activator (tPA) on embolic stroke. METHODS: Rats subjected to
      embolic middle cerebral artery occlusion (MCAO) were treated with rhEPO (5000
      U/kg) in combination with tPA (10 mg/kg) at 2 or 6 hours after MCAO. Control
      groups consisted of ischemic rats treated with rhEPO (5000 U/kg) alone, tPA (10
      mg/kg) alone, or saline at 2 or 6 hours after MCAO. RESULTS: The combination
      therapy of rhEPO and tPA initiated 6 hours after MCAO did not reduce the ischemic
      lesion volume and significantly (P<0.05) increased the incidence of brain
      hemorrhage measured by frequency of gross hemorrhage and a quantitative
      spectrophotometric hemoglobin assay compared with rats treated with rhEPO alone
      and tPA alone. However, when the combination therapy was initiated 2 hours after
      MCAO, the treatment significantly (P<0.05) reduced the lesion volume and did not
      substantially increase the incidence of hemorrhagic transformation compared with
      saline-treated rats. Immunostaining analysis revealed that the combination
      therapy of rhEPO and tPA at 6 hours significantly (P<0.05) increased matrix
      metalloproteinase-9, NF-kappaB, and interleukin-1 receptor-associated kinase-1
      immunoreactive cerebral vessels compared with rats treated with rhEPO alone and
      saline. CONCLUSIONS: EPO exacerbates tPA-induced brain hemorrhage without
      reduction of ischemic brain damage when administered 6 hours after stroke in a
      rat model of embolic MCAO and that matrix metalloproteinase-9, NF-kappaB, and
      interleukin-1 receptor-associated kinase-1 upregulated by the delayed combination
      therapy may contribute to augmentation of brain hemorrhage.

PMID- 20671253
TI  - Increased risk of stroke associated with nonsteroidal anti-inflammatory drugs: a
      nationwide case-crossover study.
AB  - BACKGROUND AND PURPOSE: Limited studies assessed cerebrovascular safety of
      individual nonsteroidal anti-inflammatory drugs (NSAIDs). We evaluated the risk
      of ischemic and hemorrhagic stroke associated with short-term use of selective
      and nonselective NSAIDs in a Chinese population with a high incidence of stroke.
      METHODS: A retrospective case-crossover study was conducted by analyzing the
      Taiwan National Health Insurance Database. We identified all ischemic and
      hemorrhagic stroke patients in 2006, aged >or=20 years, based on International
      Classification of Diseases, 9th Revision, Clinical Modification diagnosis codes
      from inpatient claims and defined the index date as the date of hospitalization.
      For each patient, we defined case period as 1 to 30 days before the index date
      and control period as 91 to 120 days before the index date. A pharmacy
      prescription database was searched for NSAID use during the case and control
      periods. We calculated adjusted ORs and their 95% CIs with a conditional logistic
      regression model. RESULTS: A total of 28 424 patients with ischemic stroke and
      9456 patients with hemorrhagic stroke were included. For ischemic stroke, a
      modest increased risk was evident for all oral NSAIDs with adjusted ORs (95% CI)
      ranging from 1.20 (1.00 to 1.44) for celecoxib to 1.90 (1.39 to 2.60) for
      ketorolac. For hemorrhagic stroke, oral ketorolac was associated with a
      significantly higher risk with OR of 2.69 (1.56 to 4.66). Significantly increased
      risk was found for parenteral NSAIDs, in particular ketorolac, with an OR of 3.92
      (3.25 to 4.72) for ischemic stroke and 5.98 (4.40 to 8.13) for hemorrhagic
      stroke. CONCLUSIONS: Use of selective and nonselective NSAIDs was associated with
      an increased risk of both ischemic and hemorrhagic stroke, strikingly high for
      parenteral ketorolac.

PMID- 20671254
TI  - Small unruptured intracranial aneurysm verification study: SUAVe study, Japan.
AB  - BACKGROUND AND PURPOSE: The natural history and optimal management of
      incidentally found small unruptured aneurysms <5 mm in size remain unclear. A
      prospective study was conducted to determine the optimal management for
      incidentally found small unruptured aneurysms. METHODS: From September 2000 to
      January, 2004, 540 aneurysms (446 patients) were registered. Four hundred forty
      eight unruptured aneurysms <5 mm in size (374 patients) have been followed up for
      a mean of 41.0 months (1306.5 person-years) to date. We calculated the average
      annual rupture rate of small unruptured aneurysms and also investigated risk
      factors that contribute to rupture and enlargement of these aneurysms. RESULTS:
      The average annual risks of rupture associated with small unruptured aneurysms
      were 0.54% overall, 0.34% for single aneurysms, and 0.95% for multiple aneurysms.
      Patient <50 years of age (P=0.046; hazard ratio, 5.23; 95% CI, 1.03 to 26.52),
      aneurysm diameter of >or=4.0 mm (P=0.023; hazard ratio, 5.86; 95% CI, 1.27 to
      26.95), hypertension (P=0.023; hazard ratio, 7.93; 95% CI, 1.33 to 47.42), and
      aneurysm multiplicity (P=0.0048; hazard ratio, 4.87; 95% CI, 1.62 to 14.65) were
      found to be significant predictive factors for rupture of small aneurysms.
      CONCLUSIONS: The annual rupture rate associated with small unruptured aneurysms
      is quite low. Careful attention should be paid to the treatment indications for
      single-type unruptured aneurysms <5 mm. If the patient is <50 years of age, has
      hypertension, and multiple aneurysms with diameters of >or=4 mm, treatment should
      be considered to prevent future aneurysmal rupture.

PMID- 20671255
TI  - A simple positron emission tomography-based calibration for perfusion-weighted
      magnetic resonance maps to optimize penumbral flow detection in acute stroke.
AB  - BACKGROUND AND PURPOSE: Perfusion-weighted (PW) MRI is increasingly used to
      identify the tissue at risk. The adequate PW-MRI map and threshold remain
      controversial due to a considerable individual variation of values. By
      comparative positron emission tomography, we evaluated a simple MR-based and
      positron emission tomography-validated calibration of PW maps. METHODS: PW-MRI
      and quantitative positron emission tomography (15O-water) of patients with acute
      stroke were used to calculate averaged as well as individual thresholds of
      penumbral flow (positron emission tomography cerebral blood flow (<20 mL/100
      g/min) for maps of time to peak, mean transit time, cerebral blood flow, and
      cerebral blood volume. A linear regression analysis studied the variability of
      the individual thresholds using 3 different PW reference regions (hemispheric,
      white matter, gray matter). The best model was used for volumetric analysis to
      compare averaged and scaled individual thresholds and to calculate look-up tables
      for PW maps. RESULTS: In 26 patients, the averaged thresholds were
      (median/interquartile range): cerebral blood flow 21.7 mL/100 g/min (19.9 to 32);
      cerebral blood volume 1.5 mL/100 g (0.9 to 1.8); mean transit time seconds 5.2
      (3.9 to 6.9); and relative time to peak 4.2 seconds (2.8 to 5.8). The large
      individual variability was best explained by the mean value of the hemispheric
      reference derived from a region of interest on a level with the basal ganglia of
      the unaffected hemisphere (R(2): cerebral blood flow 0.76, cerebral blood volume
      0.55, mean transit time 0.83, time to peak 0.95). Hemispheric reference-corrected
      thresholds clearly improved the detection of penumbral flow. Look-up tables were
      calculated to identify the individual thresholds according to the hemispheric
      reference value. CONCLUSIONS: The individual variation of PW values, even if
      calculated by deconvolution, remains a major obstacle in quantitative PW imaging
      and can be significantly improved by a simple MR-based calibration. Easily
      applicable look-up tables identify the individual best threshold for each PW map
      to optimize mismatch detection.

PMID- 20671256
TI  - Early depressed mood after stroke predicts long-term disability: the Northern
      Manhattan Stroke Study (NOMASS).
AB  - BACKGROUND AND PURPOSE: Depression is highly prevalent after stroke and may
      influence recovery. We aimed to determine whether depressed mood acutely after
      stroke predicts subsequent disability and mortality. METHODS: As part of the
      Northern Manhattan Stroke Study, a population-based incident stroke case follow
      up study performed in a multiethnic urban population, participants were asked
      about depressed mood within 7 to 10 days after stroke. Participants were followed
      every 6 months the first 2 years and yearly thereafter for 5 years for death and
      disability measured by the Barthel Index. We fitted polytomous logistic
      regression models using a canonical link to examine the association between
      depressed mood after stroke and disability comparing moderate (Barthel Index 60
      to 95) and severe (Barthel Index <60) disability with no disability (Barthel
      Index >or=95). Cox proportional hazards models were created to examine the
      association between depressed mood and mortality. RESULTS: A question about
      depressed mood within 7 to 10 days after stroke was asked in 340 of 655 patients
      with ischemic stroke enrolled, and 139 reported that they felt depressed. In
      multivariate analyses controlling for sociodemographic factors, stroke severity,
      and medical conditions, depressed mood was associated with a greater odds of
      severe disability compared with no disability at 1 (OR 2.91, 95% CI 1.07 to 7.91)
      and 2 years (OR 3.72, 95% CI 1.29 to 10.71) after stroke. Depressed mood was not
      associated with all-cause mortality or vascular death. CONCLUSIONS: Depressed
      mood after stroke is associated with disability but not mortality after stroke.
      Early screening and intervention for mood disorders after stroke may improve
      outcomes and requires further research.

PMID- 20671257
TI  - Cortical neuromodulation modifies cerebral vasomotor reactivity.
AB  - BACKGROUND AND PURPOSE: Cerebral vasomotor reactivity (VMR) is a capability of
      cerebral vessels to dilate in response to hypercapnia. Transcranial direct
      current stimulation (tDCS) effects on cerebral hemodynamics have been poorly
      studied. METHODS: Ten healthy subjects underwent anodal/cathodal tDCS on the left
      motor cortex. Before and after tDCS, VMR assessment by transcranial Doppler and
      an electrocardiogram were performed. Normalized low-frequency band power of heart
      rate variability and its reactivity from basal to VMR condition (LFN(react)) were
      estimated as relative markers of sympathetic activation. tDCS exerted a polarity
      specific effect on both VMR (P=0.0001) and LFN(react) (P=0.001). Anodal tDCS
      decreased VMR by 3.4%/mm Hg CO(2) bilaterally and increased LFN(react), whereas
      cathodal tDCS increased VMR by 0.8%/mm Hg CO(2) bilaterally and reduced
      LFN(react). CONCLUSIONS: Cerebral VMR is modified by tDCS. Based on the
      consensual changes with heart rate variability, we can hypothesize that the
      sympathetic nervous system could modulate the bihemispheric modification of VMR.
      Further studies are needed to confirm this hypothesis.

PMID- 20671258
TI  - High myeloid-related protein: 8/14 levels are related to an increased risk of
      cardiovascular events after carotid endarterectomy.
AB  - BACKGROUND AND PURPOSE: Myeloid-related protein (Mrp) 8/14 complex is the
      functional relevant form of Mrp-8 and Mrp-14. Mrp-8/14 complex is actively formed
      in the cytoplasm of circulating neutrophils and monocytes and then secreted.
      Plasma Mrp-8/14 complex is emerging as a new biomarker that may discriminate
      between patients with an acute coronary syndrome and those with stable coronary
      heart disease. Little is known about the predictive value of Mrp-8/14 plaque and
      plasma levels for cardiovascular events after atherectomy. METHODS: Plasma and
      plaque Mrp-8/14 levels were determined by ELISA in 230 consecutive patients (mean
      age 73) who underwent carotid endarterectomy. Patients were followed for 3 years
      for recurrent cardiovascular events (vascular death, nonfatal vascular event, and
      peripheral intervention). During follow-up, 62 patients experienced an event.
      Baseline Mrp-8/14 levels were higher in patients who experienced an event than in
      event-free patients (plasma 0.78+/-0.63 versus 0.57+/-0.67 mg/L; P=0.030 and
      plaque 0.54+/-1.23 versus 0.08+/-1.51 mg/kg; P=0.027). In a Cox model, a 1 U
      increase in log Mrp-8/14 was associated with an increased risk of recurrent
      events (plasma, hazard ratio [HR], 1.51; 95% CI, 1.02 to 2.23, P=0.040; and
      plaque, HR, 1.23, 95% CI, 1.04 to 1.46, P=0.018). After multivariate adjustment
      for risk factors (both plasma and plaque Mrp-8/14) and plaque characteristics
      (only plaque Mrp-8/14), the HR remained the same for both plasma (HR, 1.50, 95%
      CI, 1.01 to 2.30; P=0.046) and plaque (HR, 1.20, 95% CI, 1.01 to 1.44; P=0.042).
      CONCLUSIONS: High Mrp-8/14 plasma and plaque levels are related to an increased
      risk of adverse cardiovascular events after a carotid endarterectomy, independent
      of traditional cardiovascular risk factors.

PMID- 20671259
TI  - Apparent benefit of water filters may be an artifact of study design.

PMID- 20671260
TI  - Florence Nightingale (1820-1910): feminism and hospital reform. 2010.

PMID- 20671261
TI  - Florence Nightingale and the Crimean War.

PMID- 20671262
TI  - Phenotypic diversity in chondromyxoid fibroma reveals differentiation pattern of
      tumor mimicking fetal cartilage canals development: an immunohistochemical study.
AB  - Chondromyxoid fibroma represents a rare benign cartilaginous tumor of young
      patients occurring in a subcortical metaphyseal location. The histogenesis of
      chondromyxoid fibroma has not yet been postulated, even though the conventional
      histology and recent immunohistochemical studies on phenotype of the mesenchymal
      cells and extracellular matrix components suggested its origin in immature
      cartilage. Therefore, we wished to compare the morphological pattern of immature
      cartilage tissue with chondromyxoid fibroma to investigate a possible
      developmental counterpart of chondromyxoid fibroma. Archival paraffin-embedded
      tissues from 4 fetal femora and 10 cases of chondromyxoid fibroma were analyzed
      simultaneously using histochemistry (safranin O) and established
      immunohistochemical antibodies (CD34, CD163, and smooth muscle actin).
      Vascularized cartilage canals growing into the fetal cartilage from the
      perichondrium displayed characteristic glomeruloid structures with central
      arterioles within the immature mesenchymal stroma and numerous superficial
      sinusoidal blood vessels accompanied by macrophage infiltration. Similarly, each
      case of chondromyxoid fibroma demonstrated admixture of two characteristic
      components: immature fibrous tissue of vascularized stroma with accumulation of
      macrophages in areas of superficial sinusoidal proliferation, and variable
      amounts of lobulated chondroid tissue. Based on the observed substantial
      morphological similarity between the cartilage canals and chondromyxoid fibroma,
      we suggest that the chondromyxoid fibroma represents a neoplasm originating from
      or mimicking the fetal cartilage canals within the immature cartilage.

PMID- 20671263
TI  - Simian immunodeficiency virus infection alters chemokine networks in lung tissues
      of cynomolgus macaques: association with Pneumocystis carinii infection.
AB  - Infection by HIV-1 frequently leads to pulmonary complications, including
      alterations to local immune environments. To better understand these alterations,
      we have examined in detail the patterns and levels of expression of chemokine,
      cytokine, and chemokine receptor mRNAs in lung tissues from 16 uninfected or
      simian immunodeficiency virus (SIV)/DeltaB670 infected cynomolgus macaques at
      different stages of infection. Among the most up-regulated immune genes were
      interferon (IFN)-gamma, IFN-gamma-inducible CXCR3 ligands, and CCR5 ligands, as
      well as the cognate chemokine receptors. These changes were greatest in animals
      with clear Pneumocystis carinii coinfection. Immunohistochemistry and in situ
      hybridization revealed monocytes/macrophages to be the predominant type of cell
      infiltrating into lung tissues and serving as the major cellular source of
      chemokines. To explore the causes of chemokine alterations, we treated macaque
      lung cells with IFN-gamma, lipopolysaccharide, Poly(I:C), and P. carinii in
      vitro, and results revealed that these stimuli can induce the expression of CXCR3
      ligand and/or CCR5 ligand mRNAs. Taken together, these studies provide a
      comprehensive definition of the chemokine networks available to modulate cellular
      recruitment to lung tissues during SIV infection and implicate both cytokines
      (IFN-gamma) and pathogens (SIV and P. carinii) as contributors to increased
      expression of pro-inflammatory chemokines.

PMID- 20671264
TI  - Hypoxia increases the expression of stem-cell markers and promotes clonogenicity
      in glioblastoma neurospheres.
AB  - Hypoxia promotes the expansion of non-neoplastic stem and precursor cell
      populations in the normal brain, and is common in malignant brain tumors. We
      examined the effects of hypoxia on stem-like cells in glioblastoma (GBM). When
      GBM-derived neurosphere cultures are grown in 1% oxygen, hypoxia-inducible factor
      1alpha (HIF1alpha) protein levels increase dramatically, and mRNA encoding other
      hypoxic response genes, such as those encoding hypoxia-inducible gene-2, lysyl
      oxidase, and vascular endothelial growth factor, are induced over 10-fold.
      Hypoxia increases the stem-like side population over fivefold, and the percentage
      of cells expressing CD133 threefold or more. Notch pathway ligands and targets
      are also induced. The rise in the stem-like fraction in GBM following hypoxia is
      paralleled by a twofold increase in clonogenicity. We believe HIF1alpha plays a
      causal role in these changes, as when oxygen-stable HIF1alpha is expressed in
      normoxic glioma cells CD133 is induced. We used digoxin, which has been shown to
      lower HIF protein levels in vitro and in vivo, to inhibit the hypoxic response.
      Digoxin suppressed HIF1alpha protein expression, HIF1alpha downstream targets,
      and slowed tumor growth in vivo. In addition, pretreatment with digoxin reduced
      GBM flank xenograft engraftment of hypoxic GBM cells, and daily intraperitoneal
      injections of digoxin were able to significantly inhibit the growth of
      established subcutaneous glioblastoma xenografts, and suppressed expression of
      vascular endothelial growth factor.

PMID- 20671265
TI  - Schistosomiasis-induced experimental pulmonary hypertension: role of interleukin
      13 signaling.
AB  - The mechanisms underlying schistosomiasis-induced pulmonary hypertension (PH),
      one of the most common causes of PH worldwide, remain unclear. We sought to
      determine whether Schistosoma mansoni causes experimental PH associated with
      pulmonary vascular remodeling in an interleukin (IL)-13-dependent manner. IL
      13Ralpha1 is the canonical IL-13 signaling receptor, whereas IL-13Ralpha2 is a
      competitive nonsignaling decoy receptor. Wild-type, IL-13Ralpha1(-/-), and IL
      13Ralpha2(-/-) C57BL/6J mice were percutaneously infected with S. mansoni
      cercariae, followed by i.v. injection of eggs. We assessed PH with right
      ventricular catheterization, histological evaluation of pulmonary vascular
      remodeling, and detection of IL-13 and transforming growth factor-beta signaling.
      Infected mice developed pulmonary peri-egg granulomas and arterial remodeling
      involving predominantly the vascular media. In addition, gain-of-function IL
      13Ralpha2(-/-) mice had exacerbated vascular remodeling and PH. Mice with loss of
      IL-13Ralpha1 function did not develop PH and had reduced pulmonary vascular
      remodeling. Moreover, the expression of resistin-like molecule-alpha, a target of
      IL-13 signaling, was increased in infected wild-type and IL-13Ralpha2(-/-) but
      not IL-13Ralpha1(-/-) mice. Phosphorylated Smad2/3, a target of transforming
      growth factor-beta signaling, was increased in both infected mice and humans with
      the disease. Our data indicate that experimental schistosomiasis causes PH and
      potentially relies on up-regulated IL-13 signaling.

PMID- 20671266
TI  - Notch3 overexpression is related to the recurrence of ovarian cancer and confers
      resistance to carboplatin.
AB  - Amplification of the Notch3 locus has been detected in ovarian high-grade serous
      carcinoma (HGSC), the most common and malignant type of ovarian cancer. We have
      previously demonstrated that ovarian cancer cells, which amplified and
      overexpressed Notch3, were dependent on Notch3 signaling for cellular survival
      and growth. In this study, we provide new evidence that Notch3 expression is
      associated with recurrent postchemotherapy HGSCs. Moreover, patients with
      recurrent HGSCs in effusion with high Notch3 expression had a significantly worse
      clinical outcome, including reduced overall survival and shortened progression
      free survival than did patients with low Notch3 expressing HGSC. Ectopic
      expression of the Notch3 intracellular domain led to an increase in IC(50) for
      carboplatin in an ovarian surface epithelial cell line and in a low-grade serous
      carcinoma cell line that expressed undetectable levels of Notch3. Interestingly,
      expression of the Notch3 intracellular domain increased expression of several
      genes associated with embryonic stem cells including Nanog, Oct4, Klf4, Rex1,
      Rif1, Sall4, and NAC1 as well as an ATP-dependent transporter gene, ABCB1.
      Knockdown of Notch3 resulted in sensitization to carboplatin in OVCAR3 that
      expresses abundant Notch3. Taken together, the above findings suggest that Notch3
      pathway activation reprograms tumor cells to assume an array of embryonic stem
      cell markers and participates in development of chemoresistance in HGSC.

PMID- 20671267
TI  - Neurokinin-1 receptor (NK1-R) expression in the brains of SIV-infected rhesus
      macaques: implications for substance P in NK1-R immune cell trafficking into the
      CNS.
AB  - Recent studies suggest a link between neuropsychiatric disorders and HIV/SIV
      infection. Most evidence indicates that monocytes/macrophages are the primary
      cell type infected within the CNS and that they contribute to CNS inflammation
      and neurological disease. Substance P (SP), a pleotropic neuropeptide implicated
      in inflammation, depression, and immune modulation via interaction with its
      cognate receptor, the neurokinin 1 receptor (NK1-R), is produced by
      monocyte/macrophages. While the presence of NK1-R on neurons is well known, its
      role on cells of the immune system such as monocyte/macrophages is just beginning
      to emerge. Therefore, we have examined the expression of SP and NK1-R and their
      relationship to SIV/HIV encephalitis (SIVE/HIVE) lesions and SIV-infected cells.
      These studies demonstrated intense expression of SP and NK1-R in SIVE lesions,
      with macrophages being the principal cell expressing NK1-R. Interestingly, all of
      the SIV-infected macrophages expressed NK1-R. Additionally, we examined the
      functional role of SP as a proinflammatory mediator of monocyte activation and
      chemotaxis. These studies demonstrated that treatment of monocytes with SP
      elicited changes in cell-surface expression for CCR5 and NK1-R in a dose
      dependent manner. Moreover, pretreatment with SP enhanced both SP- and CCL5
      mediated chemotaxis. All of these findings suggest that SP and NK1-R are
      important in SIV infection of macrophages and the development of SIVE lesions.

PMID- 20671268
TI  - Engineered zinc finger nuclease-mediated homologous recombination of the human
      rhodopsin gene.
AB  - PURPOSE: Novel zinc finger nucleases (ZFNs) were designed to target the human
      rhodopsin gene and induce homologous recombination of a donor DNA fragment.
      METHODS: Three-finger zinc finger nucleases were designed based on previously
      published guidelines. To assay for ZFN specificity, the authors generated human
      embryonic retinoblast cell lines stably expressing a Pro23His rhodopsin, the most
      common mutation associated with autosomal dominant retinitis pigmentosa in North
      America. They report quantification of these rhodopsin-specific ZFNs to induce a
      targeted double-strand break in the human genome, demonstrate their ability to
      induce homologous recombination of a donor DNA fragment, and report the
      quantification of the frequency of ZFN-mediated homologous recombination.
      RESULTS: Compared with endogenous homologous recombination, the authors observed
      a 12-fold increase in homologous recombination and an absolute frequency of ZFN
      directed homologous recombination as high as 17% in the human rhodopsin gene.
      CONCLUSIONS: ZFNs are chimeric proteins with significant potential for the
      treatment of inherited diseases. In this study, the authors report the design of
      novel ZFNs targeting the human rhodopsin gene. These ZFNs may be useful for the
      treatment of retinal diseases such as retinitis pigmentosa, one of the most
      common causes of inherited blindness in the developed world. Herein, they also
      report on several aspects of donor fragment design and in vitro conditions that
      facilitate ZFN-mediated homologous recombination.

PMID- 20671269
TI  - Driving with hemianopia, II: lane position and steering in a driving simulator.
AB  - PURPOSE: The hypothesis that drivers with homonymous hemianopia (HH) would take a
      lane position that increased the safety margin on their blind side was tested
      with a driving simulator. METHODS: Twelve participants with HH (six right HH and
      six left; nine men; mean age, 50 years; range 31-72), and 12 matched current
      drivers with normal vision (NV) each completed approximately 120 minutes of
      simulator driving. Lane position and steering stability were evaluated for
      specific road segment types (straight segments, curves, and turns) in city and
      rural undivided highway driving. RESULTS: The drivers with right HH held a lane
      position significantly (P = 0.001) to the left of NV drivers on the straight road
      segments and to a lesser extent on the curves. The drivers with left HH had a
      lane position similar to that of the NV drivers on straights and curves, but
      followed a significantly (P = 0.005) more rightward path on the left turns.
      CONCLUSIONS: The results support the hypothesis that drivers with HH take a lane
      position that increases the safety margin on their blind side; however, absolute
      lane position varies as the steering maneuver and location of the risk from
      oncoming traffic change with road segment type.

PMID- 20671270
TI  - Dichoptic suppression of mfVEP amplitude: effect of retinal eccentricity and
      simulated unilateral visual impairment.
AB  - PURPOSE: To investigate the effect of retinal eccentricity on the phenomenon of
      dichoptic suppression of the mfVEP amplitude and to examine the relationship
      between the degree of simulated unilateral visual impairment and the possible
      release of dichoptic suppression in the contralateral eye. METHOD: Eight subjects
      with corrected visual acuity (VAc) >6/6 and stereoacuity >60 sec arc underwent
      monocular and dichoptic pattern-pulse mfVEP. Dichoptic stimulation was repeated
      with refractively induced blur of one eye with +4-D and +6-D lenses above
      distance correction. RESULTS: Dichoptic recording resulted in significant
      reduction of averaged mfVEP amplitude (19.8% +/- 4.9%, paired t-test, P =
      0.00003). The magnitude of suppression, while statistically significant at all
      eccentricities, was significantly larger in the central part of the visual field
      and diminished toward the periphery. Refractive blur, used to simulate visual
      impairment produced variable degrees of amplitude reduction in the blurred eye
      and resulted in amplitude increases in the contralateral eye. There was a highly
      significant correlation between the magnitude of amplitude reduction in the
      blurred eye and increase in amplitude (i.e., release of dichoptic suppression) in
      the contralateral eye (r = 0.91, P < 0.0001). CONCLUSIONS: The study demonstrated
      that dichoptic stimulation results in eccentricity-dependent suppression of mfVEP
      amplitude. Factors affecting visual performance of one eye (monocular blur)
      promote the release of dichoptic suppression in the fellow (unaffected) eye. This
      phenomenon leads to an increase in intereye asymmetry and therefore may improve
      early detection of ocular diseases, especially monocular pathologic processes.

PMID- 20671271
TI  - Retinal venous oxygen saturation increases by flicker light stimulation.
AB  - PURPOSE: Luminance flicker stimulation of the photoreceptors is known to increase
      retinal blood flow. Elevated blood velocity was determined using laser Doppler
      velocimetry, and increased vascular diameters during flicker were observed by
      measurements with a retinal vessel analyzer. Oxygen supply may be the target of
      the regulation of retinal blood flow. Thus, the oxygen saturation (SO(2)) in
      retinal arterioles and venules was investigated along with their diameters.
      METHODS: Dual-wavelength (548 nm and 610 nm) fundus images were taken in 19
      healthy volunteers (mean age, 26 +/- 2.5 years) before (baseline) and during
      luminance flicker stimulation (12.5 Hz; modulation depth, 1:25). Retinal vessel
      SO(2) (dual-wavelength optical oximetry) and diameters (central retinal arterial
      and venous equivalents [CRAE and CRVE]) were determined. RESULTS: CRAEs and CRVEs
      of 193 +/- 20 MUm and 228 +/- 20 MUm at baseline increased statistically
      significant to a maximum of 202 +/- 19 MUm (P < 0.0005) and 242 +/- 17 MUm (P <
      0.0005), respectively, under flicker stimulation. Although the arterial SO(2)
      remained unchanged at 98%-99%, an increase of the venous saturation from 60% +/-
      5.7% to 64% +/- 5.9% (P < 0.0005) was found. CONCLUSIONS: In agreement with
      earlier investigations, the vessel dilation found here indicates an elevation of
      retinal blood flow by luminance flicker stimulation. This increase of the flow
      should meet the enhanced metabolic need of the neural retina under a
      physiological stimulus. The augmentation of venous oxygenation may indicate a
      higher capillary oxygen concentration, necessary to provide a sufficient
      diffusion rate of oxygen from the capillaries to the inner retinal tissue.

PMID- 20671272
TI  - Increased intraocular pressure in mice treated with dexamethasone.
AB  - PURPOSE: Glucocorticoids are potent modulators of the immune system and are
      useful in treating systemic and ocular diseases, but they can increase
      intraocular pressure (IOP) in susceptible persons. Steroid-induced ocular
      hypertension resembles several characteristics observed in primary open angle
      glaucoma (POAG). Elucidating genetic and environmental mechanisms impacting
      steroid-induced ocular hypertension may provide important insight into
      pathophysiological drivers of POAG. The purpose of this study was to create a
      mouse model of steroid-induced ocular hypertension. METHODS: Osmotic mini-pumps
      delivering dexamethasone or PBS were implanted into C57BL/6J-Tyr(c-Brd) *
      129S5/SvEvBrd (B6.129) mice. Repeated IOP measurements were obtained over a 4
      week study using a tonometer before and after pump implantation. Body weights,
      complete blood counts (CBCs), and blood pressure were obtained to further
      characterize the model. Pharmacologic effects of timolol, latanoprost, and Y
      39983 were studied in hypertensive mice. RESULTS: Administration of dexamethasone
      to B6.129 hybrid mice resulted in significant increases in IOP in most animals
      compared with baseline or mice treated with PBS. No significant change in IOP was
      observed in PBS-treated mice. Interestingly, dexamethasone failed to increase IOP
      in a subset of mice, though steroid delivery was successful as measured using CBC
      analysis. Moreover, topical agents that lower IOP in normotensive mice also
      produced significant decreases in mice exhibiting elevated IOP in response to
      dexamethasone. CONCLUSIONS: Systemic treatment with dexamethasone significantly
      increased IOP in most genetically heterogeneous mice used in this study. This
      mouse model should facilitate studies aimed at understanding mechanisms affecting
      steroid-induced ocular hypertension in humans.

PMID- 20671273
TI  - Shotgun lipidomic analysis of human meibomian gland secretions with electrospray
      ionization tandem mass spectrometry.
AB  - PURPOSE: The purpose of this investigation was to determine the major molecular
      components of the lipids in normal human meibomian gland secretions (meibum).
      METHODS: The meibum samples were studied by direct infusion electrospray
      ionization (ESI), quadrupole time-of-flight mass spectrometry, and tandem mass
      spectrometry (MS/MS) analysis, in both positive and negative detection modes.
      RESULTS: Hundreds of peaks were detected, among which the molecular compositions
      and subclasses of approximately 160 major peaks were confidently identified. The
      compositions and subclasses of these peaks were determined from collision-induced
      dissociation fragmentation patterns, high-resolution and high-mass-accuracy
      spectra, and references of literature reports. The major peaks detected in
      positive mode were those of nonpolar lipids, including wax esters, cholesteryl
      esters, triacylglycerols, and diesters, whereas in negative mode, the major peaks
      detected were those of polar lipids, including free fatty acids and (O-acyl)
      omega-hydroxy fatty acids. CONCLUSIONS: The analysis of intact lipids in meibum
      with direct infusion ESI-MS/MS analysis has the advantages of minimal sample
      preparation (no chromatography or pre-separation needed), mild experimental
      conditions, high throughput, and high sensitivity.

PMID- 20671274
TI  - Two distinct aquaporin 0s required for development and transparency of the
      zebrafish lens.
AB  - PURPOSE: AQP0, formerly known as MIP26, likely has multiple separate functions in
      the mammalian lens, including water transport, formation of thin junctions, and
      interactions with other lens components. Although mammalian genomes contain only
      one Aqp0 gene, the zebrafish genome contains two, Aqp0a and Aqp0b, and the
      putative multiple functions of the single mammalian protein may be divided
      between these two genes. The purpose of this study was to exploit this gene
      duplication and divergence to illuminate the multiple functions of AQP0 in the
      lens. METHODS: Wholemount in situ hybridization and Western blot analyses were
      used to determine the expression pattern of Aqp0a and Aqp0b. The role of both
      proteins was studied in vivo by microinjection of antisense morpholino
      oligonucleotides in zebrafish. The water permeability of both proteins was tested
      using the Xenopus oocyte swelling assay and a yeast shrinkage assay. RESULTS:
      Both genes, like their mammalian counterpart, are expressed in the lens.
      Morpholino knock-down of either gene alone led to cataract formation, indicating
      that both genes are necessary for normal lens development and transparency. Full
      length Aqp0a is a functional water channel when expressed in Xenopus oocytes and
      in yeast, whereas Aqp0b was not. However, the addition of an HA-tag at its N
      terminus converted Aqp0b to a water channel in Xenopus oocytes. CONCLUSIONS:
      These results suggest that Aqp0a is the primary water channel of the lens and
      that Aqp0b, though possibly a secondary water channel, has an unidentified
      function in the lens.

PMID- 20671275
TI  - Association of interleukin-1beta (IL1B) polymorphisms with Graves' ophthalmopathy
      in Taiwan Chinese patients.
AB  - PURPOSE: To evaluate whether variations in the IL1B gene could be associated with
      Graves' ophthalmopathy (GO) in patients with Graves' disease (GD). METHOD: This
      case-control study included 471 Taiwan Chinese patients with GD (200 with GO and
      271 without GO) and 160 healthy volunteers. Eight single-nucleotide polymorphisms
      (SNPs) in IL1B were genotyped with an allele-specific extension and ligation
      assay. RESULTS: In the IL1B SNPs examined, the C allele of rs1143634 was
      associated with GD, whereas the T/T genotype of the SNPs rs1143634 and rs16944
      were less associated with the disease. The A/A genotype of the SNPs rs3917368 and
      rs1143643, which had the strongest interaction, may increase the risk of GO (P =
      0.024 and P = 0.017, respectively). Several GD susceptibility and
      insusceptibility IL1B haplotypes have been identified, and the Ht4-GCGCCTCC
      haplotype, composed of eight SNPs and associated with low circulating IL1beta
      levels, may be protective against the development of GO (P = 0.025). Moreover,
      that the GO-susceptible genotype was associated with lower plasma IL1beta
      concentrations implies that the origin of GO may go beyond the IL1B polymorphism
      associated elevation of circulating IL1beta. CONCLUSIONS: The data for IL1B
      polymorphisms and the association of GD and GO with plasma IL1beta levels show
      that IL1B polymorphisms may be associated with the development of GD and GO.

PMID- 20671276
TI  - In vitro screening for angiostatic potential of herbal chemicals.
AB  - PURPOSE: Herbal medicine has long been used in traditional medicinal systems. The
      authors carried out a first-line screening of four herbal chemicals with reported
      antioxidative properties and capabilities to suppress endothelial cell growth and
      migration. These herbal chemicals were isoliquiritigenin (ISL) from licorice,
      epigallocatechin gallate (EGCG) from green tea, resveratrol (Rst) from grapes,
      and gambogic acid (GA) from the resin of Garcinia hanburyi. METHODS: Cytotoxicity
      was studied by MTT cell viability/proliferation assay on human retinal pigment
      epithelial cells (ARPE19). Effects on vascular endothelial growth factor (VEGF)
      induced endothelial cell proliferation and migration were investigated by a
      scratch-wound model using human umbilical vein endothelial cells (HUVECs). The
      effects on VEGF signaling in HUVECs were analyzed by Western blotting. RESULTS:
      At sub-cytotoxic levels, ISL (10 MUM), EGCG (50 MUM), and Rst (10 MUM) suppressed
      HUVEC proliferation and migration under VEGF (20 ng/mL) stimulation in our
      scratch-wound model. HUVEC migration was reduced more by ISL and EGCG than
      bevacizumab, a humanized monoclonal antibody against VEGF. The efficiency of Rst
      was similar to that of bevacizumab. GA, however, was toxic to cells even at
      nanomolar concentrations. Western blot analysis showed that these chemicals
      affected focal adhesion kinase activation and expression of pigment epithelial
      growth factor. CONCLUSIONS: ISL, EGCG, and Rst are highly effective and efficient
      in suppressing endothelial cell proliferation and migration, with low
      cytotoxicity on ARPE19 and HUVEC lines. They are potentially useful for further
      investigation to develop antiangiogenic therapies by virtue of their small
      molecular sizes for easy penetration through tissue cells and their low effective
      dosages.

PMID- 20671277
TI  - The relationship between body and ambient temperature and corneal temperature.
AB  - PURPOSE: Exposure to elevated ambient temperatures has been mentioned as a risk
      factor for common eye diseases, primarily presbyopia and cataract. The aim of the
      present study was to examine the relationship among ambient, cornea, and body
      core temperature. METHODS: The relation between corneal temperature and ambient
      temperature was examined in 11 human volunteers. Furthermore, corneal temperature
      was measured using a thermal camera during elevation of body core temperature in
      three human volunteers and four rats. RESULTS: A linear relationship between
      corneal temperature and body temperature was found in the rat. For humans there
      was an initial linear increase in corneal temperature with increasing body
      temperature, but corneal temperature seemed to plateau at 36.5 degrees C to 37.0
      degrees C despite a continued increase of body core temperature. A linear
      relationship between ambient and corneal temperature was found in humans but with
      a less steep slope than that between corneal and body core temperature.
      CONCLUSIONS: Corneal temperature is estimated to reach the maximum of 36.5
      degrees C to 37.0 degrees C at ambient temperatures between 32.0 degrees C and
      34.5 degrees C. If there is a causal relationship between elevated eye
      temperature, cataract, and presbyopia, the incidence of these eye diseases is
      predicted to increase with global warming. Importantly, the strong association
      between corneal temperature and body core temperature indicates that frequent
      infections could also be considered a risk factor for age-related lens disorders.

PMID- 20671278
TI  - Sensitivity loss in early glaucoma can be mapped to an enlargement of the area of
      complete spatial summation.
AB  - PURPOSE: The area of complete spatial summation (Ricco's area) is the largest
      stimulus size for which area * intensity is constant at threshold. The authors
      sought to investigate whether Ricco's area changes in early glaucoma to account
      for the decreased visual signal/noise ratio that may accompany retinal ganglion
      cell loss. METHODS: Spatial summation functions were measured, and Ricco's area
      was determined at four 10 degrees  retinal locations in 24 patients with early
      glaucoma (total deviation at test locations, mean, -1.3 dB; range, +2 dB to -8
      dB) and 26 age-similar healthy subjects under achromatic and S-cone isolation
      conditions. Achromatic grating resolution acuity was measured at the same
      locations to estimate functional ganglion cell density. RESULTS: Ricco's area was
      enlarged in patients compared with controls for both achromatic (enlarged by:
      superior field, 0.57 log units, P < 0.01; inferior field, 0.72 log units, P <
      0.01) and chromatic (enlarged by: superior field, 0.26 log units, P < 0.01;
      inferior field, 0.25 log units, P = 0.065) stimuli, with negligible vertical
      summation curve shifts along the intensity axis. Resolution acuity was
      significantly reduced in glaucoma patients in both hemifields (P < 0.001). There
      was a weak, but significant, relationship between Ricco's area and resolution
      acuity. CONCLUSIONS: Enlargement of Ricco's area completely compensates for
      reduced perimetric sensitivity in early glaucoma to maintain constant threshold
      at Ricco's area, suggesting an increase in signal pooling in response to ganglion
      cell loss. The rightward displacement of the spatial summation curve indicates
      that perimetric stimuli should be capable of modulating in size as well
      as/instead of contrast, which may boost the glaucoma signal within measurement
      noise.

PMID- 20671279
TI  - Identification of the Raf-1 signaling pathway used by cAMP to inhibit p42/p44
      MAPK in rat lacrimal gland acini: role in potentiation of protein secretion.
AB  - PURPOSE: The lacrimal gland is primarily responsible for the aqueous portion of
      the tear film. Simultaneous addition of cholinergic agonists or growth factors
      with cAMP-dependent agonists potentiates secretion. Recent investigations
      revealed that cAMP decreases p44/p42 mitogen-activated protein kinase (MAPK)
      activity stimulated by cholinergic agonists and growth factors that could account
      for this potentiation. In this study the authors identify the signal transduction
      pathway used by cAMP to inhibit MAPK activity. METHODS: Rat lacrimal gland acini
      were incubated with H89, an inhibitor of protein kinase A, before the addition of
      dibutyryl cAMP (dbcAMP, 10(-3) M) for 30 minutes. Basal MAPK and CREB activity
      and MAPK activity after stimulation with the cholinergic agonist carbachol (Cch)
      or epidermal growth factor (EGF) for 5 minutes was determined. The effect of
      dbcAMP on EGF receptor activity and basal and stimulated Ras, Raf-1, mitogen
      activated protein kinase kinase (MEK), and MAPK activity was determined. The
      effect of a Rap-1 inhibitor, GGTI-298, on MAPK activity after the addition of
      dbcAMP was also determined. RESULTS: H89 relieved the inhibition of cAMP on MAPK
      activity and inhibited CREB activity. Incubation with dbcAMP did not have any
      effect either on the EGF receptor or on Ras but significantly inhibited both
      basal and Raf-1 and MEK activity stimulated with Cch or EGF. GGTI-298 did not
      have any effect on cAMP-dependent decrease in MAPK activity. CONCLUSIONS: The
      authors conclude that cAMP mediates the inhibition of MAPK by PKA in a Raf-1
      dependent manner.

PMID- 20671281
TI  - Beneficial read-through of a USH1C nonsense mutation by designed aminoglycoside
      NB30 in the retina.
AB  - PURPOSE: The human Usher syndrome (USH) is the most frequent cause of inherited
      combined deaf-blindness. USH is clinically and genetically heterogeneous,
      assigned to three clinical types. The most severe type is USH1, characterized by
      profound inner ear defects and retinitis pigmentosa. Thus far, no effective
      treatment for the ophthalmic component of USH exists. The p.R31X nonsense
      mutation in USH1C leads to a disease causing premature termination of gene
      translation. Here, we investigated the capability of the novel synthetic
      aminoglycoside NB30 for the translational read-through of the USH1C-p.R31X
      nonsense mutation as a retinal therapy option. METHODS: Read-through of p.R31X by
      three commercial, clinically applied aminoglycosides and the synthetic derivative
      NB30 was validated in vitro, in cell culture, and in retinal explants.
      Restoration of harmonin functions was monitored in GST pull-downs (scaffold
      function) and by F-actin bundling analysis in HEK293T cells. Biocompatibility of
      aminoglycosides was determined in retinal explants by TUNEL assays. RESULTS: In
      vitro translation and analyses of transfected HEK293T cells revealed a dose
      dependent read-through by all aminoglycosides. In addition, gentamicin,
      paromomycin, and NB30 induced read-through of p.R31X in mouse retinal explants.
      The read-through of p.R31X restored harmonin protein function. In contrast to all
      commercial aminoglycosides NB30 showed good biocompatibility. CONCLUSIONS:
      Commercial aminoglycosides and NB30 induced significant read-through of the USH1C
      p.R31X nonsense mutation. However, the observed read-through efficiency, along
      with its significantly reduced toxicity and good biocompatibility, indicate that
      the novel derivate NB30 represents a better choice than commercial
      aminoglycosides in a read-through therapy of USH1C and other ocular diseases.

PMID- 20671280
TI  - Dynamic patterns of histone lysine methylation in the developing retina.
AB  - PURPOSE: Histone lysine methylation (HKM) is an important epigenetic mechanism
      that establishes cell-specific gene expression and functions in development.
      However, epigenetic control of retinal development is poorly understood. To study
      the roles of HKM in retinogenesis, the authors examined the dynamic changes of
      three HKM modifications and of two of their regulators, the histone
      methyltransferases (HMTases) Ezh2 and G9a, in the mouse retina. METHODS: Retinal
      sections and lysates from embryonic day 16 through adult were processed for
      immunohistochemistry and immunoblotting using antibodies against various marks
      and HMTases. To further analyze the biological functions of HKM, the effects of
      small molecule inhibitors of HMTases were examined in vitro. RESULTS: Methylation
      marks of trimethyl lysine 4 and 27 on histone H3 (H3K4me3 and H3K27me3) were
      detected primarily in differentiated retinal neurons in the embryonic and adult
      retina. In contrast, dimethyl lysine 9 on histone H3 (H3K9me2) was noted in early
      differentiating retinal ganglion cells but was lost after birth. The HMTases
      controlling H3K27me3, H3K9me2, Ezh2, and G9a were enriched in the inner embryonic
      retina during the period of active retinogenesis. Using the chemical inhibitors
      of Ezh2 and G9a, the authors reveal a role for HKM in regulating retinal neuron
      survival. CONCLUSIONS: HKM is a dynamic and spatiotemporally regulated process in
      the developing retina. Epigenetic regulation of gene transcription by Ezh2- and
      G9a-mediated HKM plays crucial roles in retinal neuron survival and may represent
      novel epigenetic targets to enhance viability in retinal neurodegenerative
      diseases such as glaucoma.

PMID- 20671282
TI  - The effect of age on the area of complete spatial summation for chromatic and
      achromatic stimuli.
AB  - PURPOSE: Previously, an association between the area of complete spatial
      summation (Ricco's area) and age under scotopic conditions had been found. The
      authors sought to determine whether Ricco's area is similarly associated with age
      under photopic achromatic and selective S-cone conditions in peripheral vision
      and whether any association relates to a loss of ganglion cell density as
      determined by measurements of peripheral grating resolution acuity. METHODS:
      Achromatic spatial summation functions were plotted for 68 healthy subjects (aged
      20-77 years) in four oblique meridians on a gray background field of 10 cd/m(2).
      Similar functions were generated for the S-cone pathway (isolated using Stiles'
      two-color threshold method) for the same locations. Ricco's area was determined
      using two-phase regression analysis. Achromatic peripheral grating resolution
      acuity was measured at the same locations using high-contrast Gabor stimuli, as
      an estimate of localized functional ganglion cell density. RESULTS: There was a
      notable decrease in overall contrast sensitivity with age for all stimulus sizes.
      However, there was no evidence of age-related change in Ricco's area for either
      achromatic (superior field, r(2) = 0.05; inferior field, r(2) = 0.0007; all P >
      0.05) or chromatic (superior field, r(2) = 0.01; inferior field, r(2) = 0.006;
      all P > 0.05) stimuli, despite a significant decrease in peripheral grating
      resolution acuity with age (superior field, r(2) = 0.15; inferior field, r(2) =
      0.17; both P < 0.05). CONCLUSIONS: An age-related decline in functional ganglion
      cell density is not accompanied by a significant change in Ricco's area for
      achromatic or chromatic stimuli.

PMID- 20671283
TI  - Retinal function and structure in Ant1-deficient mice.
AB  - PURPOSE: Mutations in ANT, a mitochondrial ATP transporter, are typically
      associated with myopathy. Because of the high metabolic demands of the retina,
      the authors examined whether elimination of the Ant1 isoform in a transgenic
      mouse affects retinal function or morphology. METHODS: RT-PCR was used to confirm
      Ant1 expression in retinas of wild-type (WT) or Ant1(-/-) mice. Full-field ERGs
      were used to test retinal function under dark- and light-adapted conditions and
      the recovery of the photoresponse to a bright flash. Using histologic methods,
      the authors assessed the retinal location of ANT and ANT1-beta-gal reporter
      protein, mitochondrial activity with cytochrome c oxidase (COX) and succinate
      dehydrogenase (SDH) staining, retinal layer thickness, and bipolar cell types
      using Chx10 and recoverin. RESULTS: Ant1(-/-) mice had supernormal ERG b-waves
      under both dark- and light-adapted conditions. X-Gal staining was detected in a
      subset of cells within the inner retina. The following characteristics were
      normal in Ant1(-/-) mice compared with age-matched WT mice: recovery of the
      photoresponse, COX and SDH activity, retinal morphology, and bipolar cell
      morphology. CONCLUSIONS: The presence of ANT1 in a subset of inner retinal cells
      accompanied by supernormal ERG responses suggests that ANT1 may be localized to
      hyperpolarizing bipolar cells. However, the immunohistochemical techniques used
      here did not show any differences in bipolar cells. Moderate functional changes
      coupled with a lack of detectable morphologic changes suggest that ANT1 is not
      essential for ATP transport in the retina.

PMID- 20671284
TI  - Temporal response properties of retinal ganglion cells in rd1 mice evoked by
      amplitude-modulated electrical pulse trains.
AB  - PURPOSE: The electrophysiological properties of degenerated retinas responding to
      amplitude-modulated electrical pulse trains were investigated to provide a
      guideline for the development of a stimulation strategy for retinal prostheses.
      METHODS: The activities of retinal ganglion cells (RGCs) in response to amplitude
      modulated pulse trains were recorded from an in vitro model of retinal
      prosthesis, which consisted of an rd1 mouse retinal patch attached to a planar
      multielectrode array. The ability of the population activities of RGCs to
      effectively represent, or encode, the information on the visual intensity time
      series, when the intensity of visual input is transformed to pulse amplitudes,
      was investigated. RESULTS: An optimal pulse amplitude range was selected so that
      RGC firing rates increased monotonically and linearly. An approximately 10-Hz
      rhythm was observed in the field potentials from degenerated retinas, which
      resulted in a rhythmic burst of spontaneous spikes. Multiple peaks were present
      in poststimulus time histograms, with interpeak intervals corresponding to the
      oscillation frequency of the field potentials. Phase resetting of the field
      potential oscillation by stimulation was consistently observed. Despite a
      prominent alteration of the properties of electrically evoked firing with respect
      to normal retinas, RGC response strengths could be modulated by pulse amplitude.
      Accordingly, the temporal information of stimulation could be faithfully
      represented in the RGC firing patterns by an amplitude-modulated pulse train.
      CONCLUSIONS: The results suggest that pulse amplitude modulation is a feasible
      means of implementing a stimulation strategy for retinal prostheses, despite the
      marked change in the physiological properties of RGCs in degenerated retinas.

PMID- 20671285
TI  - In vivo analysis of ciliary muscle morphologic changes with accommodation and
      axial ametropia.
AB  - PURPOSE: To use anterior segment optical coherence tomography (AS-OCT) to analyze
      ciliary muscle morphology and changes with accommodation and axial ametropia.
      METHODS: Fifty prepresbyopic volunteers, aged 19 to 34 years were recruited. High
      resolution images were acquired of nasal and temporal ciliary muscles in the
      relaxed state and at stimulus vergence levels of -4 and -8 D. Objective
      accommodative responses and axial lengths were also recorded. Two-way, mixed
      factor analyses of variance (ANOVAs) were used to assess the changes in ciliary
      muscle parameters with accommodation and determine whether these changes are
      dependent on the nasal-temporal aspect or axial length, whereas linear regression
      analysis was used to analyze the relationship between axial length and ciliary
      muscle length. RESULTS: The ciliary muscle was longer (r = 0.34, P = 0.02), but
      not significantly thicker (F = 2.84, P = 0.06), in eyes with greater axial
      length. With accommodation, the ciliary muscle showed a contractile shortening (F
      = 42.9. P < 0.001), particularly anteriorly (F = 177.2, P < 0.001), and a
      thickening of the anterior portion (F= 46.2, P < 0.001). The ciliary muscle was
      thicker (F = 17.8, P < 0.001) and showed a greater contractile response on the
      temporal side. CONCLUSIONS: The accommodative changes observed support an
      anterior, as well as centripetal, contractile shift of ciliary muscle mass.

PMID- 20671286
TI  - An in silico model of scanning laser tomography image series: an alternative
      benchmark for the specificity of progression algorithms.
AB  - PURPOSE: There is no gold-standard measurement of glaucomatous structural
      progression against which to validate software progression algorithms. A computer
      model was developed and validated to simulate stable series of Heidelberg Retina
      Tomograph II (HRT; Heidelberg Engineering, Heidelberg, Germany) images, with
      realistic topographic variability, suitable for benchmarking false-positive rates
      of progression algorithms. METHODS: Three confocal image stacks were selected
      from each of five sets of HRT II scans, obtained within 6 weeks in 127 eyes of 66
      patients. For each eye, a simulated series was propagated from one baseline
      confocal stack by adding fixational eye movements, photon-counting, and
      electronic measurement noise. Simulated confocal stacks were imported into the
      HRT software to generate topography images. Real and simulated image comparisons
      were quantified with the mean pixel height standard deviation (MPHSD), image
      cross-correlation (CC) of pixel-wise variability maps, and the rim area (RA)
      coefficient of variation (CV). RESULTS: The mean difference (95% limits of
      agreement; LoA) in MPHSD between real and simulated images was 3.5 MUm (-20.9 to
      28.8 MUm) within mean topographies and 2.0 MUm (-5.4 to 9.3 MUm) between mean
      topographies. The mean CC between real and simulated spatial variability maps was
      0.58 within mean topographies and 0.54 between mean topographies. The mean
      difference (95% LoA) between real and simulated mean topography RA CV was -2.1% (
      17.6% to +13.4%). Variability about anatomic features was well reproduced.
      CONCLUSIONS: Simulation realistically reproduces variability in real, stable
      images acquired over a short period. Stability in clinical datasets is uncertain,
      whereas in these modeled series, it is certain. This method provides benchmark
      datasets on which the specificity of progression algorithms can be tested.

PMID- 20671287
TI  - Hyperopic refractive error and shorter axial length are associated with age
      related macular degeneration: the Singapore Malay Eye Study.
AB  - PURPOSE: To describe the association between refractive errors, ocular biometry,
      and age-related macular degeneration (AMD) in an Asian Malay population in
      Singapore. METHODS: A population-based study of 3280 Malay individuals aged 40 to
      80 years was conducted in Singapore. Early- and late-AMD signs were graded from
      retinal photographs according to the Wisconsin grading system. Autorefraction,
      followed by subjective refraction, was performed to obtain spherical equivalent
      refraction (SER) in diopters, with emmetropia defined as SER -0.5 to +0.5 D,
      hyperopia as > +0.5 D, and myopia as < -0.5 D. Partial coherence laser
      interferometry was used to measure axial length, anterior chamber depth, and
      corneal curvature. The association between refractive status, ocular biometry and
      the prevalence of both early and late AMD were analyzed. RESULTS: Hyperopic
      refractive error (odds ratio [OR] 1.54; 95% confidence interval [CI] 1.00-2.36;
      compared with myopia, P = 0.05), shorter axial length (OR, 1.91; CI, 1.05-3.46,
      comparing 1st vs. 4th quartiles; P = 0.03), and steeper corneal curvature (OR,
      1.93; CI, 1.16-3.20, comparing 1st vs. 4th quartiles, P = 0.01) were
      significantly associated with early AMD, after adjustment for age, sex, smoking,
      education, height, and systolic blood pressure. Each diopter increase in
      hyperopic refraction and each millimeter decrease in axial length was associated
      with an 8% (OR, 1.08; CI, 1.01-1.16; P = 0.03) and 29% (OR, 1.29; CI, 1.06-1.57;
      P = 0.01) increased risk of early AMD, respectively. No significant association
      was noted of refractive error and ocular biometry with late AMD. CONCLUSIONS:
      Hyperopic refractive error and shorter axial length are associated with early AMD
      in Asian eyes.

PMID- 20671288
TI  - Effects of anisometropic amblyopia on visuomotor behavior, I: saccadic eye
      movements.
AB  - PURPOSE: Impairment of spatiotemporal visual processing is the hallmark of
      amblyopia, but its effects on eye movements during visuomotor tasks have rarely
      been studied. Here the authors investigate how visual deficits in anisometropic
      amblyopia affect saccadic eye movements. METHODS: Thirteen patients with
      anisometropic amblyopia and 13 control subjects participated. Participants
      executed saccades and manual reaching movements to a target presented randomly 5
      degrees  or 10 degrees  to the left or right of fixation in three viewing
      conditions: binocular, amblyopic, and fellow eye viewing. Latency, amplitude, and
      peak velocity of primary and corrective saccades were measured. RESULTS:
      Initiation of primary saccades was delayed and more variable when patients viewed
      monocularly with their amblyopic eye. During binocular viewing, saccadic latency
      exhibited increased variability and no binocular advantage in patients (i.e.,
      mean latency was similar to that during fellow eye viewing). Mean amplitude and
      peak velocity of primary saccades were comparable between patients and control
      subjects; however, patients exhibited greater variability in saccade amplitude.
      The frequency of corrective saccades was greater when patients viewed with their
      fellow eye than it was with binocular or amblyopic eye viewing. Latency,
      amplitude, and peak velocity of corrective saccades in patients were normal in
      all viewing conditions. CONCLUSIONS: Saccades had longer latency and decreased
      precision in amblyopia. Once saccades were initiated, however, the dynamics of
      saccades were not altered. These findings suggest that amblyopia is associated
      with slower visual processing in the afferent (sensory) pathway rather than a
      deficit in the efferent (motor) pathway of the saccadic system.

PMID- 20671289
TI  - A porcine model of selective retinal capillary closure induced by embolization
      with fluorescent microspheres.
AB  - PURPOSE: To investigate the feasibility of creating an animal model of selective
      retinal capillary closure to mimic the capillary closure that occurs in diabetic
      retinopathy. METHODS: Fluorescent microspheres of 10- or 15-MUm diameter were
      delivered to one eye of anesthetized pigs via a customized cannula advanced
      through the carotid arterial system to the origin of the external ophthalmic
      artery that supplies blood to the eye in this species. After preliminary trials
      in 10 pigs, embolization was performed in one eye of 34 animals that were allowed
      to survive for 7, 14, or 28 days. Embolized eyes were assessed by fluorescein
      angiography, electroretinography (ERG), and, after enucleation, light (LM) and
      electron (EM) microscopy. RESULTS: The microspheres were detectable in the retina
      immediately after embolization, were restricted to the nerve fiber layer of the
      retina, and remained thereafter within the retina for periods up to 28 days. They
      effectively occluded embolized capillaries and some precapillary arterioles. No
      systemic or cerebral adverse effects were noted, thus allowing survival and
      subsequent follow-up. Embolization caused a reduction in the b-wave amplitude and
      the oscillatory potentials of the rod-cone bright-flash ERG but did not affect
      the amplitude of the a-wave. Embolization induced extracellular and intracellular
      edema confined to the inner and mid retina, and as a result the retinas of
      embolized eyes were thicker than those of fellow, nonembolized eyes. The outer
      retina and RPE were unaffected. CONCLUSIONS: This survival model of retinal
      embolization with microspheres should be useful in the study of the retinal
      effects of the capillary closure that may occur in diabetic eyes.

PMID- 20671290
TI  - Altered expression of retinal molecular markers in the canine RPE65 model of
      Leber congenital amaurosis.
AB  - PURPOSE: Leber congenital amaurosis (LCA) is a group of childhood-onset retinal
      diseases characterized by severe visual impairment or blindness. One form is
      caused by mutations in the RPE65 gene, which encodes the retinal pigment
      epithelium (RPE) isomerase. In this study, the retinal structure and expression
      of molecular markers for different retinal cell types were characterized, and
      differences between control and RPE65 mutant dogs during the temporal evolution
      of the disease were analyzed. METHODS: Retinas from normal and mutant dogs of
      different ages were examined by immunofluorescence with a panel of 16 different
      antibodies. RESULTS: Cones and rods were preserved in the mutant retinas, and the
      number of cones was normal. However, there was altered expression of cone
      arrestin and delocalization of rod opsin. The ON bipolar cells showed sprouting
      of the dendritic arbors toward the outer nuclear layer (ONL) and retraction of
      their axons in the inner nuclear layer (INL). A decreased expression of GABA, and
      an increased expression of intermediate filament glial markers was also found in
      the mutant retinas. These changes were more evident in the adult than the young
      mutant retinas. CONCLUSIONS: The structure of the retina is well preserved in the
      mutant retina, but several molecular changes take place in photoreceptors and in
      bipolar and amacrine cells. Some of these changes are structural, whereas others
      reflect a change in localization of the examined proteins. This study provides
      new information that can be applied to the interpretation of outcomes of retinal
      gene therapy in animal models and humans.

PMID- 20671291
TI  - Cardiac oxytocin receptor blockade stimulates adverse cardiac remodeling in
      ovariectomized spontaneously hypertensive rats.
AB  - An increasing amount of evidence demonstrates the beneficial role of oxytocin
      (OT) in the cardiovascular system. Similar actions are attributed to genistein,
      an isoflavonic phytoestrogen. The treatment with genistein activates the OT
      system in the aorta of ovariectomized (OVX) Sprague-Dawley (SD) rats. The
      objective of this study was to determine the effects of low doses of genistein on
      the OT-induced effects in rat hypertension. The hypothesis tested was that
      treatment of OVX spontaneously hypertensive rats (SHRs) with genistein improves
      heart structure and heart work through a mechanism involving the specific OT
      receptor (OTR). OVX SHRs or SD rats were treated with genistein (in microg/g body
      wt sc, 10 days) in the presence or absence of an OT antagonist (OTA)
      [d(CH(2))(5), Tyr(Me)(2), Orn(8)]-vasotocin or a nonspecific estrogen receptor
      antagonist (ICI-182780). Vehicle-treated OVX rats served as controls. RT-PCR and
      Western blot analysis demonstrated that left ventricular (LV) OTR, downregulated
      by ovariectomy, increased in response to genistein. In SHRs or SD rats, this
      effect was blocked by OTA or ICI-182780 administration. The OTR was mainly
      localized in microvessels expressing the CD31 marker and colocalized with
      endothelial nitric oxide synthase. In SHRs, the genistein-stimulated OTR
      increases were associated with improved fractional shortening, decreased blood
      pressure (12 mmHg), decreased heart weight-to-body weight ratio, decreased
      fibrosis, and lowered brain natriuretic peptide in the LV. The prominent finding
      of the study is the detrimental effect of OTA treatment on the LV of SHRs. OTA
      treatment of OVX SHRs resulted in a dramatic worsening of ejection fractions and
      an augmented fibrosis. In conclusion, these results demonstrate that cardiac OTRs
      are involved in the regulation of cardiac function of OVX SHRs. The decreases of
      OTRs may contribute to cardiac pathology following menopause.

PMID- 20671292
TI  - Without 'informed consent'? Ethics and ancient mummy research.
AB  - Ethical issues are of foremost importance in modern bio-medical science. Ethical
      guidelines and socio-cultural public awareness exist for modern samples, whereas
      for ancient mummy studies both are de facto lacking. This is particularly
      striking considering the fact that examinations are done without informed consent
      or that the investigations are invasive due to technological aspects and that it
      affects personality traits. The aim of this study is to show the pro and contra
      arguments of ancient mummy research from an ethical point of view with a
      particular focus on the various stakeholders involved in this research. Relevant
      stakeholders in addition to the examined individual are, for example, a
      particular researcher, and the science community in general, likely descendents
      of the mummy or any future generation. Our broad discussion of the moral dilemma
      of mummy research should help to extract relevant decision-making criteria for
      any such study in future. We specifically do not make any recommendations about
      how to rate these decision-factors, since this is highly dependent on temporal
      and cultural affiliations of the involved researcher. The sustainability of
      modern mummy research is dependent on ethical orientation, which can only be
      given and eventually settled in an interdisciplinary approach such as the one we
      attempt to present here.

PMID- 20671293
TI  - A brief survey of first-in-human studies.
AB  - First-in-human (FIH) studies are a critical step in the drug development process
      and typically aim to characterize a compound's pharmacokinetics, potential
      effective concentration or dose, and safety or tolerability margins. Although
      effort continues to enhance the predictive quality of the selection of FIH doses
      from preclinical data, and little consensus is available on the design and
      conduct of FIH studies, detailed surveys describing general approaches taken in
      FIH studies are useful in the optimization of early-phase clinical drug
      development. Although allometric scaling techniques continue to provide poor
      predictive estimates for human pharmacokinetic parameters, FIH starting doses are
      selected with substantial safety factors applied to human equivalent dose, often
      in excess of regulatory guidelines. Based on these examples, it appears that
      relatively conservative 2-fold dose escalations are the most common escalation
      approach within FIH single ascending dose studies. The combination of
      conservative dose escalations with low starting doses can result in large FIH
      trials, consuming both time and resources. Approaches that could enhance the
      predictive nature of a compound's disposition and adaptive nature of FIH studies
      could provide a tremendous benefit for drug development.

PMID- 20671294
TI  - Effect of three different injection sites on the pharmacokinetics of the once
      daily human GLP-1 analogue liraglutide.

PMID- 20671295
TI  - Comparison of the behavioral and cardiovascular effects of intranasal and oral d
      amphetamine in healthy human subjects.
AB  - Recent reports indicate an increase in intranasal use of prescription oral
      stimulant medication. However, there do not appear to be any published clinical
      studies that have characterized the behavioral and cardiovascular effects of
      intranasally administered d-amphetamine, which is commonly prescribed for
      Attention Deficit Hyperactivity Disorder. In this study, a range of d-amphetamine
      doses (0, 16, 24, and 32 mg/70 kg) were administered as an intranasal solution
      delivered using a mucosal atomization device. Equal oral doses were included for
      comparison. Assessments were conducted before and at regular intervals for 3
      hours following drug administration and included self-reported drug-effect
      questionnaires, cardiovascular indices, a performance task, and 2 measures of
      impulsivity. d-Amphetamine produced prototypical stimulant effects (eg, increased
      subject ratings of Stimulated and Like Drug, elevated heart rate and blood
      pressure, and improved rate and accuracy on the digit symbol substitution task)
      irrespective of dose, but the onset of these effects was generally earlier
      following intranasal administration, with significant effects emerging 15 to 30
      minutes after intranasal dosing and 45 to 60 minutes after oral dosing. These
      results demonstrate that intranasal administration of d-amphetamine results in a
      more rapid onset compared to oral dosing, which could be associated with the
      popularity of intranasal prescription stimulant use and an enhanced potential for
      abuse.

PMID- 20671296
TI  - Using team-based learning to teach clinical pharmacology in medical school:
      student satisfaction and improved performance.
AB  - Formal teaching in clinical pharmacology was never part of the curriculum at the
      American University of Beirut Faculty of Medicine. Based on feedback from
      students and on recommendations of academic bodies, we have introduced, since
      June 2008, twice-monthly "rational prescribing" sessions during the required
      internal medicine rotation in year 4 of medical school. All sessions were
      designed according to the innovative Team-based Learning format and concluded by
      having the students practice prescription writing and personal formulary
      development based on the World Health Organization criteria. Our 18-month
      experience showed that students were very satisfied with the course and the
      teaching approach, and that their performance on prescription writing and
      formulary development had improved. Although further studies are needed to
      explore the impact of team-based learning on additional performance measures, we
      recommend it as an effective alternative for teaching clinical pharmacology in
      medical schools.

PMID- 20671297
TI  - Re: Efflux transporter-mediated interactions with atorvastatin--interesting
      findings with multiple substrates: istradefylline, verapamil, and rifampicin.

PMID- 20671298
TI  - Effects of feeding bile acids and a bile acid sequestrant on hepatic bile acid
      composition in mice.
AB  - An improved ultra performance liquid chromatography-tandem mass spectrometry
      (UPLC/MS/MS) method was established for the simultaneous analysis of various bile
      acids (BA) and applied to investigate liver BA content in C57BL/6 mice fed 1%
      cholic acid (CA), 0.3% deoxycholic acid (DCA), 0.3% chenodeoxycholic acid (CDCA),
      0.3% lithocholic acid (LCA), 3% ursodeoxycholic acid (UDCA), or 2% cholestyramine
      (resin). Results indicate that mice have a remarkable ability to maintain liver
      BA concentrations. The BA profiles in mouse livers were similar between CA and
      DCA feedings, as well as between CDCA and LCA feedings. The mRNA expression of
      Cytochrome P450 7a1 (Cyp7a1) was suppressed by all BA feedings, whereas Cyp7b1
      was suppressed only by CA and UDCA feedings. Gender differences in liver BA
      composition were observed after feeding CA, DCA, CDCA, and LCA, but they were not
      prominent after feeding UDCA. Sulfation of CA and CDCA was found at the 7-OH
      position, and it was increased by feeding CA or CDCA more in male than female
      mice. In contrast, sulfation of LCA and taurolithocholic acid (TLCA) was female
      predominant, and it was increased by feeding UDCA and LCA. In summary, the
      present systematic study on BA metabolism in mice will aid in interpreting BA
      mediated gene regulation and hepatotoxicity.

PMID- 20671300
TI  - I am many: the reconstruction of self following acquired brain injury.
AB  - In this article we examine the construction of self following acquired brain
      injury from an experience-centered perspective. Life history and semistructured
      interview transcripts collected from four brain injury survivors were analyzed
      using thematic, syntactic, and deep structure analysis. Though notions of the
      "lost" or "shattered" self have dominated discussions of personhood in the
      acquired brain injury literature, we argue that this perspective is a crude
      representation of the postinjury experience of self, and that aspects of
      stability, recovery, transcendence, and moral growth are also involved in this
      process. We highlight the intersubjective nature of the self, and present the
      processes of delegitimation, invalidation, negotiation, and resistance as crucial
      aspects of the postinjury construction of personhood. We explore the implications
      of this complex process of construction of self for grief and bereavement
      theories, clinical practice, and professional discourse in the area of acquired
      brain injury.

PMID- 20671299
TI  - Lipidomics reveals a remarkable diversity of lipids in human plasma.
AB  - The focus of the present study was to define the human plasma lipidome and to
      establish novel analytical methodologies to quantify the large spectrum of plasma
      lipids. Partial lipid analysis is now a regular part of every patient's blood
      test and physicians readily and regularly prescribe drugs that alter the levels
      of major plasma lipids such as cholesterol and triglycerides. Plasma contains
      many thousands of distinct lipid molecular species that fall into six main
      categories including fatty acyls, glycerolipids, glycerophospholipids,
      sphingolipids, sterols, and prenols. The physiological contributions of these
      diverse lipids and how their levels change in response to therapy remain largely
      unknown. As a first step toward answering these questions, we provide herein an
      in-depth lipidomics analysis of a pooled human plasma obtained from healthy
      individuals after overnight fasting and with a gender balance and an ethnic
      distribution that is representative of the US population. In total, we
      quantitatively assessed the levels of over 500 distinct molecular species
      distributed among the main lipid categories. As more information is obtained
      regarding the roles of individual lipids in health and disease, it seems likely
      that future blood tests will include an ever increasing number of these lipid
      molecules.

PMID- 20671301
TI  - Learning formative skills of nursing practice in an accelerated program.
AB  - The purpose of this qualitative research study was to describe how students in an
      accelerated master's degree entry program experientially learned the practice of
      nursing. One research question examined in this study was: What formative
      experiences did students identify as helping them develop and differentiate their
      clinical practice? Data from clinical observations and a combination of small
      group and individual interviews were collected and analyzed using interpretive
      phenomenological methods. Students identified formative skills learned through
      the independent care of a patient as pivotal in their identity and agency
      development. By experiencing the responsibility and action from within the body
      and from within concrete situations, students developed a new understanding that
      changed their embodied ways of perceiving and orienting to the situation, as well
      as their skills and sense of agency.

PMID- 20671302
TI  - A comparative analysis of three online appraisal instruments' ability to assess
      validity in qualitative research.
AB  - The concept of validity has been a central component in critical appraisal
      exercises evaluating the methodological quality of quantitative studies.
      Reactions by qualitative researchers have been mixed in relation to whether or
      not validity should be applied to qualitative research and if so, what criteria
      should be used to distinguish high-quality articles from others. We compared
      three online critical appraisal instruments' ability to facilitate an assessment
      of validity. Many reviewers have used the critical appraisal skills program
      (CASP) tool to complete their critical appraisal exercise; however, CASP appears
      to be less sensitive to aspects of validity than the evaluation tool for
      qualitative studies (ETQS) and the Joanna Briggs Institute (JBI) tool. The ETQS
      provides detailed instructions on how to interpret criteria; however, it is the
      JBI tool, with its focus on congruity, that appears to be the most coherent.

PMID- 20671303
TI  - "Taking care of business": alcohol as currency in transactional sexual
      relationships among players in Cape Town, South Africa.
AB  - In this article we examine the dynamics of social relationships in which alcohol
      use and risky sexual behaviors cooccur. As part of a larger biological and
      behavioral HIV surveillance survey, 20 men who lived in an urban, informal
      settlement on the outskirts of Cape Town, South Africa participated in in-depth
      interviews. Interview transcripts were analyzed according to a latent content
      analysis. Findings highlight the latent association between alcohol and
      transactional sex, and enable an in-depth examination of the normative role that
      alcohol plays in the formation of casual sexual partnerships characterized by
      exchange. We build on an existing conceptual model that traces the potential
      pathways by which alcohol use and transactional sex are linked to sexual risk
      behaviors. The study findings point to the need for multilevel HIV risk-reduction
      interventions among men to reduce excessive alcohol use, risky sexual behaviors,
      and underlying perceptions of ideal masculinity.

PMID- 20671304
TI  - Unexpected identification of bilateral masses in an asymptomatic heavy smoker.

PMID- 20671305
TI  - Increased expression of 5-hydroxytryptamine2A/B receptors in idiopathic pulmonary
      fibrosis: a rationale for therapeutic intervention.
AB  - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) has a poor prognosis and limited
      responsiveness to available treatments. It is characterised by epithelial cell
      injury, fibroblast activation and proliferation and extracellular matrix
      deposition. Serotonin (5-hydroxytryptamine; 5-HT) induces fibroblast
      proliferation via the 5-HTR(2A) and 5-HTR(2B) receptors, but its
      pathophysiological role in IPF remains unclear. A study was undertaken to
      determine the expression of 5-HT receptors in IPF and experimental lung fibrosis
      and to investigate the effects of therapeutic inhibition of 5-HTR(2A/B)
      signalling on lung fibrosis in vivo and in vitro. METHODS AND RESULTS:
      Quantitative RT-PCR showed that the expression of 5-HTR(1A/B) and 5-HTR(2B) was
      significantly increased in the lungs of patients with IPF (n=12) and in those
      with non-specific interstitial pneumonia (NSIP, n=6) compared with transplant
      donors (n=12). The expression of 5-HTR(2A) was increased specifically in IPF
      lungs but not in NSIP lungs. While 5-HTR(2A) protein largely localised to
      fibroblasts, 5-HTR(2B) localised to the epithelium. To assess the effects of
      5HTR(2A/B) inhibition on fibrogenesis in vivo, mice were subjected to bleomycin
      induced lung fibrosis and treated with the 5-HTR(2A/B) antagonist terguride (or
      vehicle) in a therapeutic approach (days 14-28 after bleomycin). Terguride
      treated mice had significantly improved lung function and histology and decreased
      collagen content compared with vehicle-treated mice. Functional in vitro studies
      showed that terguride is a potent inhibitor of transforming growth factor beta(1)
      or WNT3a-induced collagen production. CONCLUSION: The studies revealed an
      increased expression of 5-HTR(2A) specifically in IPF. Blockade of 5-HTR(2A/B)
      signalling by terguride reversed lung fibrosis and is thus a promising
      therapeutic approach for IPF.

PMID- 20671306
TI  - Granulomatosis with polyangitis (Wegener's).

PMID- 20671307
TI  - Exhaled nitric oxide thresholds associated with a sputum eosinophil count >=3% in
      a cohort of unselected patients with asthma.
AB  - BACKGROUND: It has been claimed that exhaled nitric oxide (FeNO) could be
      regarded as a surrogate marker for sputum eosinophil count in patients with
      asthma. However, the FeNO threshold value that identifies a sputum eosinophil
      count >=3% in an unselected population of patients with asthma has been poorly
      studied. METHODS: This retrospective study was conducted in 295 patients with
      asthma aged 15-84 years recruited from the asthma clinic of University Hospital
      of Liege. Receiver-operating characteristic (ROC) curve and logistic regression
      analysis were used to assess the relationship between sputum eosinophil count and
      FeNO, taking into account covariates such as inhaled corticosteroids (ICS),
      smoking, atopy, age and sex. RESULTS: Derived from the ROC curve, FeNO >=41 ppb
      gave 65% sensitivity and 79% specificity (AUC=0.777, p=0.0001) for identifying a
      sputum eosinophil count >=3%. Using logistic regression analysis, a threshold of
      42 ppb was found to discriminate between eosinophilic and non-eosinophilic asthma
      (p<0.0001). Patients receiving high doses of ICS (>=1000 MUg beclometasone) had a
      significantly lower FeNO threshold (27 ppb) than the rest of the group (48 ppb,
      p<0.05). Atopy also significantly altered the threshold (49 ppb for atopic vs 30
      ppb for non-atopic patients, p<0.05) and there was a trend for a lower threshold
      in smokers (27 ppb) compared with non-smokers (46 ppb, p=0.066). Age and sex did
      not affect the relationship between FeNO and sputum eosinophilia. When combining
      all variables into the logistic model, FeNO (p<0.0001), high-dose ICS (p<0.05)
      and smoking (p<0.05) were independent predictors of sputum eosinophilia, while
      there was a trend for atopy (p=0.086). CONCLUSION: FeNO is able to identify a
      sputum eosinophil count >=3% with reasonable accuracy and thresholds which vary
      according to dose of ICS, smoking and atopy.

PMID- 20671308
TI  - Paraneoplastic thrombus or relapse of a pulmonary artery sarcoma?

PMID- 20671309
TI  - An update on contraindications for lung function testing.
AB  - Guidelines on contraindications for lung function tests have been based on expert
      opinion from >30 years ago. High-risk contraindications to lung function testing
      are associated with cardiovascular complications such as myocardial infarct,
      pulmonary embolism or ascending aortic aneurysm. Slightly less risky but still
      serious contraindications are predominantly centred on recovery from major
      thoracic, abdominal or head surgery. Less serious surgical procedures will
      present a possible risk, but the RR depends upon whether the lung function is
      essential or can wait until the patient's condition improves. In recent decades
      there have been moves towards less invasive surgical techniques, keyhole surgery
      and new technology such as laser surgery which minimise the amount of collateral
      damage to surrounding tissues. In thoracic surgery there is a shift in emphasis
      to quicker postsurgical mobility. Furthermore there has been little analysis of
      the scientific facts behind the current recommendations and contraindications.
      The principle absolute and relative contraindications are in need of revision,
      and recommended times of abstaining from lung function tests needs to be
      reviewed. This review aims to outline the key issues and suggests newer
      recommendations for contraindications for performing lung function using a risk
      matrix, as well as offering alternative approaches to testing patients who may be
      at risk of complication from testing. In general, the previous recommendation of
      waiting for 6 weeks after surgical procedures or medical complications before
      performing lung function can often now be reduced to <3 weeks with modern less
      invasive surgical techniques.

PMID- 20671310
TI  - Identifying supportive and palliative care needs in people with a recent
      diagnosis of thoracic cancer: acceptability of the SPARC questionnaire.

PMID- 20671311
TI  - Multiple pulmonary nodules: and if it was not a cancer.

PMID- 20671312
TI  - Oral delivery of protein drugs: driver for personalized medicine.
AB  - The pathogenesis of common diseases, such as metabolic diseases, is caused by the
      complex and individual interplay of many susceptibility genes, which necessitates
      both personalized diagnosis and therapy. Small-molecule drugs which adequately
      address the multiple tissue-specific target proteins affected probably will not
      become available in near future. In contrast, therapeutic proteins, such as
      growth factors and antibodies, specifically replacing or inactivating the
      corresponding susceptibility gene products, are currently being identified with
      increasing efficacy. However, the failure to be administered by the oral route
      and to reach the cytoplasm of the diseased cells typically prevents their
      therapeutic use. Recent developments suggest that these limitations may be
      overcome by encapsulation of therapeutic proteins into nanoparticles or their
      covalent modification with glycolipid (glycosylphosphatidylinositol, GPI)
      structures. These act as membrane anchors for so-called GPI-anchored proteins and
      direct certain attached passenger proteins from lipid raft areas of the plasma
      membrane via cytoplasmic lipid droplets into small vesicles. These leave the
      donor cells and transfer the GPI-anchored proteins into the cytoplasm of acceptor
      cells. This pathway may enable the transport of therapeutic proteins across the
      intestinal barrier into the circulation and eventually across the plasma membrane
      of the diseased target cells. For therapy, a number of challenges remains to be
      tackled, in particular, control of release from the GPI anchor which determines
      the pharmacokinetic and pharmacodynamic profiles. Together these findings nourish
      the hope that oral path finding to drug targets by encapsulation and covalent
      modification of therapeutic proteins may enable personalized therapy of common
      diseases.

PMID- 20671313
TI  - Classification of protein-protein interaction full-text documents using text and
      citation network features.
AB  - We participated (as Team 9) in the Article Classification Task of the Biocreative
      II.5 Challenge: binary classification of full-text documents relevant for protein
      protein interaction. We used two distinct classifiers for the online and offline
      challenges: 1) the lightweight Variable Trigonometric Threshold (VTT) linear
      classifier we successfully introduced in BioCreative 2 for binary classification
      of abstracts and 2) a novel Naive Bayes classifier using features from the
      citation network of the relevant literature. We supplemented the supplied
      training data with full-text documents from the MIPS database. The lightweight
      VTT classifier was very competitive in this new full-text scenario: it was a top
      performing submission in this task, taking into account the rank product of the
      Area Under the interpolated precision and recall Curve, Accuracy, Balanced F
      Score, and Matthew's Correlation Coefficient performance measures. The novel
      citation network classifier for the biomedical text mining domain, while not a
      top performing classifier in the challenge, performed above the central tendency
      of all submissions, and therefore indicates a promising new avenue to investigate
      further in bibliome informatics.

PMID- 20671314
TI  - Empirical investigations into full-text protein interaction Article
      Categorization Task (ACT) in the BioCreative II.5 Challenge.
AB  - The selection of protein interaction documents is one important application for
      biology research and has a direct impact on the quality of downstream BioNLP
      applications, i.e., information extraction and retrieval, summarization, QA, etc.
      The BioCreative II.5 Challenge Article Categorization task (ACT) involves doing a
      binary text classification to determine whether a given structured full-text
      article contains protein interaction information. This may be the first attempt
      at classification of full-text protein interaction documents in wide community.
      In this paper, we compare and evaluate the effectiveness of different section
      types in full-text articles for text classification. Moreover, in practice, the
      less number of true-positive samples results in unstable performance and
      unreliable classifier trained on it. Previous research on learning with skewed
      class distributions has altered the class distribution using oversampling and
      downsampling. We also investigate the skewed protein interaction classification
      and analyze the effect of various issues related to the choice of external
      sources, oversampling training sets, classifiers, etc. We report on the various
      factors above to show that 1) a full-text biomedical article contains a wealth of
      scientific information important to users that may not be completely represented
      by abstracts and/or keywords, which improves the accuracy performance of
      classification and 2) reinforcing true-positive samples significantly increases
      the accuracy and stability performance of classification.

PMID- 20671315
TI  - BioLMiner System: interaction normalization task and interaction pair task in the
      BioCreative II.5 challenge.
AB  - This paper describes a Biological Literature Miner (BioLMiner) system and its
      implementation. BioLMiner is a text mining system for biological literature,
      whose purpose is to extract useful information from biological literature,
      including gene and protein names, normalized gene and protein names, and protein
      protein interaction pairs. BioLMiner has three main subsystems in a pipeline
      structure: a gene mention recognizer (GMRer), a gene normalizer (GNer), and a
      protein-protein interaction pair extractor (PPIEor). All these subsystems are
      developed based on the machine learning techniques including support vector
      machines (SVMs) and conditional random fields (CRFs) together with carefully
      designed informative features. At the same time, BioLMiner makes use of some
      biological specific resources and existing natural language processing tools. In
      order to evaluate and compare BioLMiner, it is adapted to participate in two
      tasks of the BioCreative II.5 challenge: interaction normalization task (INT)
      using GNer and interaction pair task (IPT) using PPIEor. Our system is among the
      highest performing systems on the two tasks from which it can be seen that GMRer
      provides a good support for the INT and IPT although its performance is not
      evaluated, and the methods developed in GNer and PPIEor are extended well to the
      BioCreative II.5 tasks.

PMID- 20671316
TI  - Extracting protein interactions from text with the unified AkaneRE event
      extraction system.
AB  - Currently, relation extraction (RE) and event extraction (EE) are the two main
      streams of biological information extraction. In 2009, the majority of these RE
      and EE research efforts were centered around the BioCreative II.5 Protein-Protein
      Interaction (PPI) challenge and the "BioNLP event extraction shared task."
      Although these challenges took somewhat different approaches, they share the same
      ultimate goal of extracting bio-knowledge from the literature. This paper
      compares the two challenge task definitions, and presents a unified system that
      was successfully applied in both these and several other PPI extraction task
      settings. The AkaneRE system has three parts: A core engine for RE, a pool of
      modules for specific solutions, and a configuration language to adapt the system
      to different tasks. The core engine is based on machine learning, using either
      Support Vector Machines or Statistical Classifiers and features extracted from
      given training data. The specific modules solve tasks like sentence boundary
      detection, tokenization, stemming, part-of-speech tagging, parsing, named entity
      recognition, generation of potential relations, generation of machine learning
      features for each relation, and finally, assignment of confidence scores and
      ranking of candidate relations. With these components, the AkaneRE system
      produces state-of-the-art results, and the system is freely available for
      academic purposes at http://www-tsujii.is.s.u-tokyo.ac.jp/satre/akane/.

PMID- 20671317
TI  - An IR-aided machine learning framework for the BioCreative II.5 Challenge.
AB  - The team at the University of Wisconsin-Milwaukee developed an information
      retrieval and machine learning framework. Our framework requires only the
      standardized training data and depends upon minimal external knowledge resources
      and minimal parsing. Within the framework, we built our text mining systems and
      participated for the first time in all three BioCreative II.5 Challenge tasks.
      The results show that our systems performed among the top five teams for raw F1
      scores in all three tasks and came in third place for the homonym ortholog F1
      scores for the INT task. The results demonstrated that our IR-based framework is
      efficient, robust, and potentially scalable.

PMID- 20671319
TI  - OntoGene in BioCreative II.5.
AB  - We describe a system for the detection of mentions of protein-protein
      interactions in the biomedical scientific literature. The original system was
      developed as a part of the OntoGene project, which focuses on using advanced
      computational linguistic techniques for text mining applications in the
      biomedical domain. In this paper, we focus in particular on the participation to
      the BioCreative II.5 challenge, where the OntoGene system achieved best-ranked
      results. Additionally, we describe a feature-analysis experiment performed after
      the challenge, which shows the unexpected result that one single feature alone
      performs better than the combination of features used in the challenge.

PMID- 20671318
TI  - Exploring species-based strategies for gene normalization.
AB  - We introduce a system developed for the BioCreative II.5 community evaluation of
      information extraction of proteins and protein interactions. The paper focuses
      primarily on the gene normalization task of recognizing protein mentions in text
      and mapping them to the appropriate database identifiers based on contextual
      clues. We outline a ""fuzzy" dictionary lookup approach to protein mention
      detection that matches regularized text to similarly regularized dictionary
      entries. We describe several different strategies for gene normalization that
      focus on species or organism mentions in the text, both globally throughout the
      document and locally in the immediate vicinity of a protein mention, and present
      the results of experimentation with a series of system variations that explore
      the effectiveness of the various normalization strategies, as well as the role of
      external knowledge sources. While our system was neither the best nor the worst
      performing system in the evaluation, the gene normalization strategies show
      promise and the system affords the opportunity to explore some of the variables
      affecting performance on the BCII.5 tasks.

PMID- 20671320
TI  - Cache-oblivious dynamic programming for bioinformatics.
AB  - We present efficient cache-oblivious algorithms for some well-studied string
      problems in bioinformatics including the longest common subsequence, global
      pairwise sequence alignment and three-way sequence alignment (or median), both
      with affine gap costs, and RNA secondary structure prediction with simple
      pseudoknots. For each of these problems, we present cache-oblivious algorithms
      that match the best-known time complexity, match or improve the best-known space
      complexity, and improve significantly over the cache-efficiency of earlier
      algorithms. We present experimental results which show that our cache-oblivious
      algorithms run faster than software and implementations based on previous best
      algorithms for these problems.

PMID- 20671321
TI  - CollHaps: a heuristic approach to haplotype inference by parsimony.
AB  - Haplotype data play a relevant role in several genetic studies, e.g., mapping of
      complex disease genes, drug design, and evolutionary studies on populations.
      However, the experimental determination of haplotypes is expensive and time
      consuming. This motivates the increasing interest in techniques for inferring
      haplotype data from genotypes, which can instead be obtained quickly and
      economically. Several such techniques are based on the maximum parsimony
      principle, which has been justified by both experimental results and theoretical
      arguments. However, the problem of haplotype inference by parsimony was shown to
      be NP-hard, thus limiting the applicability of exact parsimony-based techniques
      to relatively small data sets. In this paper, we introduce collapse rule, a
      generalization of the well-known Clark's rule, and describe a new heuristic
      algorithm for haplotype inference (implemented in a program called CollHaps),
      based on parsimony and the iterative application of collapse rules. The
      performance of CollHaps is tested on several data sets. The experiments show that
      CollHaps enables the user to process large data sets obtaining very
      "parsimonious" solutions in short processing times. They also show a correlation,
      especially for large data sets, between parsimony and correct reconstruction,
      supporting the validity of the parsimony principle to produce accurate solutions.

PMID- 20671322
TI  - Combinatorial analysis for sequence and spatial motif discovery in short sequence
      fragments.
AB  - Motifs are overrepresented sequence or spatial patterns appearing in proteins.
      They often play important roles in maintaining protein stability and in
      facilitating protein function. When motifs are located in short sequence
      fragments, as in transmembrane domains that are only 6-20 residues in length, and
      when there is only very limited data, it is difficult to identify motifs. In this
      study, we introduce combinatorial models based on permutation for assessing
      statistically significant sequence and spatial patterns in short sequences. We
      show that our method can uncover previously unknown sequence and spatial motifs
      in beta-barrel membrane proteins and that our method outperforms existing methods
      in detecting statistically significant motifs in this data set. Last, we discuss
      implications of motif analysis for problems involving short sequences in other
      families of proteins.

PMID- 20671323
TI  - Nonnegative principal component analysis for cancer molecular pattern discovery.
AB  - As a well-established feature selection algorithm, principal component analysis
      (PCA) is often combined with the state-of-the-art classification algorithms to
      identify cancer molecular patterns in microarray data. However, the algorithm's
      global feature selection mechanism prevents it from effectively capturing the
      latent data structures in the high-dimensional data. In this study, we
      investigate the benefit of adding nonnegative constraints on PCA and develop a
      nonnegative principal component analysis algorithm (NPCA) to overcome the global
      nature of PCA. A novel classification algorithm NPCA-SVM is proposed for
      microarray data pattern discovery. We report strong classification results from
      the NPCA-SVM algorithm on five benchmark microarray data sets by direct
      comparison with other related algorithms. We have also proved mathematically and
      interpreted biologically that microarray data will inevitably encounter
      overfitting for an SVM/PCA-SVM learning machine under a Gaussian kernel. In
      addition, we demonstrate that nonnegative principal component analysis can be
      used to capture meaningful biomarkers effectively.

PMID- 20671324
TI  - SCS: signal, context, and structure features for genome-wide human promoter
      recognition.
AB  - This paper integrates the signal, context, and structure features for genome-wide
      human promoter recognition, which is important in improving genome annotation and
      analyzing transcriptional regulation without experimental supports of ESTs,
      cDNAs, or mRNAs. First, CpG islands are salient biological signals associated
      with approximately 50 percent of mammalian promoters. Second, the genomic context
      of promoters may have biological significance, which is based on n-mers
      (sequences of n bases long) and their statistics estimated from training samples.
      Third, sequence-dependent DNA flexibility originates from DNA 3D structures and
      plays an important role in guiding transcription factors to the target site in
      promoters. Employing decision trees, we combine above signal, context, and
      structure features to build a hierarchical promoter recognition system called
      SCS. Experimental results on controlled data sets and the entire human genome
      demonstrate that SCS is significantly superior in terms of sensitivity and
      specificity as compared to other state-of-the-art methods. The SCS promoter
      recognition system is available online as supplemental materials for academic use
      and can be found on the Computer Society Digital Library at
      http://doi.ieeecomputersociety.org/10.1109/TCBB.2008.95.

PMID- 20671325
TI  - A study of hierarchical and flat classification of proteins.
AB  - Automatic classification of proteins using machine learning is an important
      problem that has received significant attention in the literature. One feature of
      this problem is that expert-defined hierarchies of protein classes exist and can
      potentially be exploited to improve classification performance. In this article,
      we investigate empirically whether this is the case for two such hierarchies. We
      compare multiclass classification techniques that exploit the information in
      those class hierarchies and those that do not, using logistic regression,
      decision trees, bagged decision trees, and support vector machines as the
      underlying base learners. In particular, we compare hierarchical and flat
      variants of ensembles of nested dichotomies. The latter have been shown to
      deliver strong classification performance in multiclass settings. We present
      experimental results for synthetic, fold recognition, enzyme classification, and
      remote homology detection data. Our results show that exploiting the class
      hierarchy improves performance on the synthetic data but not in the case of the
      protein classification problems. Based on this, we recommend that strong flat
      multiclass methods be used as a baseline to establish the benefit of exploiting
      class hierarchies in this area.

PMID- 20671328
TI  - Guided imagery and mind-body medicine.

PMID- 20671326
TI  - On the complexity of uSPR distance.
AB  - We show that subtree prune and regraft (uSPR) distance on unrooted trees is fixed
      parameter tractable with respect to the distance. We also make progress on a
      conjecture of Steel on the preservation of uSPR distance under chain reduction,
      improving on lower bounds of Hickey et al.

PMID- 20671329
TI  - Relaxation training and guided imagery for an elderly man with bladder cancer: a
      case report.
AB  - Bladder cancer is one of the most common malignancies in elderly patients. This
      report describes the use of cue-controlled progressive relaxation training and
      guided imagery with an elderly man who was diagnosed with bladder carcinoma in
      situ. After 7 therapy sessions over 4 weeks, the posttherapy surgical pathology
      report showed "no invasive malignancy identified" for urothelial carcinoma in
      situ. A computed tomography scan showed no incidence of metastatic disease and
      that the "bladder appeared normal." Although this is a single case report, it
      should encourage further study and investigation using this alternative therapy
      for cancer patients.

PMID- 20671330
TI  - The biobehavioral effects of relaxation guided imagery on maternal stress.
AB  - PURPOSE: The purpose of this pilot study was to investigate the effects of
      relaxation-guided imagery (R-GI) on perceived stress, anxiety, and corticotropin
      releasing hormone (CRH) levels in pregnant African American women beginning in
      the second trimester. METHODS: This prospective, longitudinal study of 59 women
      used a controlled randomized experimental design with two groups conducted over
      12 weeks. The intervention was a set of three R-GI CDs developed and sequenced to
      influence study outcomes. Study measures included the Perceived Stress Scale
      (PSS), State-Trait Anxiety Inventory, and plasma CRH levels collected at three
      time points. Participants completed a daily Numeric Rating Scale of Stress (NRSS)
      and daily practice logs, which provided information on intervention use in the R
      GI group. FINDINGS: State anxiety significantly decreased over time in the R-GI
      group, and it increased over time in the usual-care (UC) group. Although a
      significant difference was not found for perceived stress, as measured by the
      PSS, the R-GI group had a greater decrease in weekly Numeric Rating Scale of
      Stress NRSS scores over time compared to the UC group. The R-GI group also had
      significant decreases in NRSS scores before and after using R-GI. There were no
      significant differences in CRH levels between groups over time. CONCLUSIONS:
      Findings support the feasibility and effectiveness of an R-GI intervention in
      reducing anxiety and daily stress levels in pregnant African American women
      beginning in the second trimester. The pilot study is an important first step in
      evaluating the effectiveness of R-GI as a primary prevention intervention to
      reduce preterm birth.

PMID- 20671331
TI  - The spirituality of feeling: An interview with Michael Jawer. Interview by Nancy
      Nachman-Hunt.
AB  - Michael Jawer is coauthor of The Spiritual Anatomy of Emotion (Park Street Press,
      2009) and has written extensively on a variety of subjects for trade and
      professional associations and for the US government. Jawer has spent the past
      decade exploring the physiological underpinnings of feeling, how it may underlie
      consciousness, how various individuals process feelings, and whether that
      processing plays a role in psychosomatic conditions such as migraine headaches,
      synesthesia, chronic fatigue, and posttraumatic stress disorder (PTSD). Mr
      Jawer's collaborator and medical editor is Marc Micozzi, MD, PhD, adjunct
      professor of physiology and biophysics at the Georgetown University School of
      Medicine, Washington DC, and editor of the first US textbook devoted to
      complementary medicine, Fundamentals of Complementary and Alternative Medicine
      (Elsevier, 1996).

PMID- 20671332
TI  - Music and meditation.

PMID- 20671333
TI  - Creative musical expression as a catalyst for quality-of-life improvement in
      inner-city adolescents placed in a court-referred residential treatment program.
AB  - BACKGROUND: Obstacles to effectively rehabilitate inner-city adolescents in staff
      secure residential treatment centers should not be underestimated. Effective
      evidence-based protocols are lacking to help juveniles who are often angry,
      detached, frustrated, and in direct conflict with their peers. Facing a myriad of
      issues ranging from youth delinquency offenses to trauma, abuse, drug/alcohol
      use, peer pressure/gang-related activities, lack of structure in home
      environments, mental health diagnoses, and cognitive functioning difficulties,
      these adolescents present extraordinary challenges to an over-stressed juvenile
      justice system. MATERIAL/METHODS: A randomized controlled crossover study is
      utilized to comprehensively evaluate the effectiveness of a novel creative
      musical expression protocol as a catalyst for nonverbal and verbal disclosure
      leading to improvements in quality of life for inner-city youth in a court
      referred residential treatment program. A total of 52 (30 females and 22 males)
      African-American, Asian, Caucasian, and Puerto Rican subjects ranging in age from
      12 to 18 (mean age 14.5) completed the study. RESULTS: Dependent variable
      measures included the Child and Adolescent Functional Assessment Scale (CAFAS),
      the Adolescent Psychopathology Scale (APS), the Adolescent Anger Rating Scale
      (AARS), the Reynolds Adolescent Depression Scale, 2nd edition (RADS 2), and the
      Adolescent Visual-Analog Recreational Music Making Assessment (A-VARMMA).
      Statistically significant (experimental vs control) improvements in multiple
      parameters include school/work role performance, total depression,
      anhedonia/negative affect, negative self-evaluation, and instrumental anger. In
      addition, extended impact (experimental vs control) is characterized by
      statistically significant improvements 6 weeks after completion of the protocol,
      for school/work role performance, behavior toward others, anhedonia/negative
      affect, total anger, instrumental anger, anger, and interpersonal problems.
      LIMITATIONS: The primary limitations of this study include an extended follow-up
      period of only 6 weeks post completion of the protocol, and the inability to
      blind the counselors performing standardized assessments. CONCLUSIONS: This study
      is the first of its kind to test a replicable creative musical expression
      protocol as a catalyst for nonverbal and verbal disclosure leading to improved
      quality of life for inner-city youth in a court-referred residential treatment
      program. With substantial potential for widespread dissemination, this innovative
      protocol for adolescents can be readily utilized by behavioral health
      professionals without prior musical experience.

PMID- 20671334
TI  - Mindfulness meditation research: issues of participant screening, safety
      procedures, and researcher training.
AB  - Increasing interest in mindfulness meditation (MM) warrants discussion of
      research safety. Side effects of meditation with possible adverse reactions are
      reported in the literature. Yet participant screening procedures, research safety
      guidelines, and standards for researcher training have not been developed and
      disseminated in the MM field of study. The goal of this paper is to summarize
      safety concerns of MM practice and offer scholars some practical tools to use in
      their research. For example, we offer screener schematics aimed at determining
      the contraindication status of potential research participants. Moreover, we
      provide information on numerous MM training options. Ours is the first
      presentation of this type aimed at helping researchers think through the safety
      and training issues presented herein. Support for our recommendations comes from
      consulting 17 primary publications and 5 secondary reports/literature reviews of
      meditation side effects. Mental health consequences were the most frequently
      reported side effects, followed by physical health then spiritual health
      consequences. For each of these categories of potential adverse effects, we offer
      MM researchers methods to assess the relative risks of each as it pertains to
      their particular research programs.

PMID- 20671335
TI  - The brain and the biology of belief: An interview with Andrew Newberg, MD.
      Interview by Nancy Nachman-Hunt.
AB  - Andrew Newberg, MD, is an associate professor in the Department of Radiology,
      Division of Nuclear Medicine, at the Hospital of the University of Pennsylvania,
      Philadelphia, with secondary appointments in the Departments of Psychiatry and
      Religious Studies. He is actively involved in neuroimaging research projects,
      including the study of the neurophysiological correlates of meditation and other
      types of complementary therapies. Dr Newberg's research now largely focuses on
      how brain function is associated with various mental states, in particular, the
      relationship between brain function and mystical or religious experiences. He has
      authored several books, including Why God Won't Go Away: Brain Science and the
      Biology of Belief (Ballantine/Random House, 2001) and coauthor with Eugene G.
      d'Aquili, MD, of The Mystical Mind: Probing the Biology of Religious Experience
      (Fortress Press, 1999). His most recent book is How God Changes Your Brain, with
      coauthor Mark Waldman (Ballantine Books, 2009).

PMID- 20671336
TI  - Imagination and healing.

PMID- 20671337
TI  - Why should guided imagery be used for surgical patients?

PMID- 20671338
TI  - A study of efficacy and cost-effectiveness of guided imagery as a portable, self
      administered, presurgical intervention delivered by a health plan.
AB  - BACKGROUND: Previous research indicates that immersive, mind-body interventions
      can improve the quality of a patient's surgical experience and clinical outcomes.
      OBJECTIVE: To describe the Blue Shield of California Presurgical Guided Imagery
      Program, assess its impact on surgical outcomes, patient satisfaction, and cost
      savings. METHOD: Analysis of survey data conducted pre- and post-surgery among
      905 eligible health plan members. Retrospective analysis of medical claims for a
      subset of 126 hysterectomy patients was compared with that of similar patients
      who did not use guided imagery for differences in length of stay and charges
      billed. RESULTS: The intervention yielded an adoption rate of 74%. Patients who
      used the guided imagery intervention reported significantly reduced anxiety and
      high levels of satisfaction. A trend toward shorter hospital stays (8% reduction,
      P=.07) was also observed in the imagery group, as well as reduced pharmaceutical
      costs (14% reduction, P=.181). In total, there was a 14% reduction in mean total
      charges billed per procedure in the imagery patients, amounting to an average
      savings of $2003 per procedure. Although it was not possible to isolate
      differential cost of lab and imaging fees for the purposes of this study, it is
      likely these factors played a part in the billing differential as well.
      DISCUSSION: Health plans are well positioned to deliver guided imagery tools for
      patient self-management prior to scheduled surgery. While mind-body interventions
      are increasingly linked to cost savings and improved outcomes in a variety of
      clinical settings, a randomized controlled trial should be conducted to firmly
      establish their efficacy.

PMID- 20671339
TI  - Mindfulness training and meditation for mental health.

PMID- 20671340
TI  - Healing mysteries: An interview with Howard Hall, PhD, PsyD. Interview by Sheldon
      Lewis.
AB  - Dr Howard Hall is an associate professor in the department of pediatrics at Case
      Western Reserve University (CWRU) and an attending doctor in the division of
      behavioral pediatrics at Rainbow Babies and Children's Hospital in Cleveland,
      Ohio. Dr Hall holds a PhD in Experimental Psychology from Princeton University
      and a PsyD in Clinical Psychology from Rutgers University. He has conducted
      research and taught courses in clinical and multicultural psychology and
      maintains a clinical practice using hypnosis and other mind-body approaches to
      healing at CWRU. Howard Hall has been recognized as a leader in the field of
      clinical psychoneuroimmunology and conducted pioneering research on the effects
      of hypnosis on immune responses. In recent years, he has studied energy-based
      rapid wound healing as demonstrated by Sufi practitioners. Recently, Sheldon
      Lewis, Editor-in-Chief of Advances in Mind-Body Medicine, spoke with Dr Hall
      about his work.

PMID- 20671341
TI  - From self-regulation to transformation.

PMID- 20671342
TI  - The relation of cancer-prone personality to exceptional recovery from cancer: a
      preliminary study.
AB  - An exceptional cancer-recovered group (n = 7) was compared with 2 other recovered
      groups: a non-exceptional cancer-recovered group (n = 27), and a non-exceptional
      heart disease (HD)-recovered group (n = 31). In support of the hypothesis that
      mitigation of a cancer-prone personality is associated with very unusual
      recoveries from cancer, the exceptional cancer group reported a greater
      prevalence of attributes of a cancer-prone personality before diagnosis and a
      greater decrease in these attributes from before diagnosis to after recovery than
      the other groups reported. Both cancer groups reported greater stress from life
      events within the 2-year period preceding diagnosis, particularly for loss (or
      threatened loss) of a close relationship, than the HD group reported. The high
      internal-consistency reliability of a Cancer-prone Personality Inventory (CPPI)
      and its discrimination of the 2 cancer groups from the HD group make it a
      promising measure of a cancer-prone personality.

PMID- 20671343
TI  - Do some people overcome cancer by mental change? Commentary on Katz/Epstein.

PMID- 20671344
TI  - Virtuous qualities of mind and health: an introduction to Davidson and Thurman.

PMID- 20671345
TI  - Emotion regulation, happiness, and the neuroplasticity of the brain.

PMID- 20671346
TI  - A Buddhist view of the skill of happiness.

PMID- 20671347
TI  - Meditation can reduce habitual responding.

PMID- 20671348
TI  - A new approach to testing the effects of group psychological therapy on length of
      life in patients with metastatic cancers.

PMID- 20671349
TI  - Psychosomatic integrative treatment and rehabilitation.

PMID- 20671351
TI  - Ventilation from four-dimensional computed tomography: density versus Jacobian
      methods.
AB  - Two calculation methods to produce ventilation images from four-dimensional
      computed tomography (4DCT) acquired without added contrast have been reported. We
      reported a method to obtain ventilation images using deformable image
      registration (DIR) and the underlying CT density information. A second method
      performs the ventilation image calculation from the DIR result alone, using the
      Jacobian determinant of the deformation field to estimate the local volume
      changes resulting from ventilation. For each of these two approaches, there are
      variations on their implementation. In this study, two implementations of the
      Jacobian-based methodology are evaluated, as well as a single density change
      based model for calculating the physiologic specific ventilation from 4DCT. In
      clinical practice, (99m)Tc-labeled aerosol single photon emission computed
      tomography (SPECT) is the standard method used to obtain ventilation images in
      patients. In this study, the distributions of ventilation obtained from the CT
      based ventilation image calculation methods are compared with those obtained from
      the clinical standard SPECT ventilation imaging. Seven patients with 4DCT imaging
      and standard (99m)Tc-labeled aerosol SPECT/CT ventilation imaging obtained on the
      same day as part of a prospective validation study were selected. The results of
      this work demonstrate the equivalence of the Jacobian-based methodologies for
      quantifying the specific ventilation on a voxel scale. Additionally, we found
      that both Jacobian- and density-change-based methods correlate well with global
      measurements of the resting tidal volume. Finally, correlation with the clinical
      SPECT was assessed using the Dice similarity coefficient, which showed
      statistically higher (p-value < 10(-4)) correlation between density-change-based
      specific ventilation and the clinical reference than did either Jacobian-based
      implementation.

PMID- 20671350
TI  - A parallel adaptive finite element simplified spherical harmonics approximation
      solver for frequency domain fluorescence molecular imaging.
AB  - Fluorescence molecular imaging/tomography may play an important future role in
      preclinical research and clinical diagnostics. Time- and frequency-domain
      fluorescence imaging can acquire more measurement information than the continuous
      wave (CW) counterpart, improving the image quality of fluorescence molecular
      tomography. Although diffusion approximation (DA) theory has been extensively
      applied in optical molecular imaging, high-order photon migration models need to
      be further investigated to match quantitation provided by nuclear imaging. In
      this paper, a frequency-domain parallel adaptive finite element solver is
      developed with simplified spherical harmonics (SP(N)) approximations. To fully
      evaluate the performance of the SP(N) approximations, a fast time-resolved
      tetrahedron-based Monte Carlo fluorescence simulator suitable for complex
      heterogeneous geometries is developed using a convolution strategy to realize the
      simulation of the fluorescence excitation and emission. The validation results
      show that high-order SP(N) can effectively correct the modeling errors of the
      diffusion equation, especially when the tissues have high absorption
      characteristics or when high modulation frequency measurements are used.
      Furthermore, the parallel adaptive mesh evolution strategy improves the modeling
      precision and the simulation speed significantly on a realistic digital mouse
      phantom. This solver is a promising platform for fluorescence molecular
      tomography using high-order approximations to the radiative transfer equation.

PMID- 20671352
TI  - Cell-survival probability at large doses: an alternative to the linear-quadratic
      model.
AB  - A model of irradiated cell survival based on rigorous accounting of
      microdosimetric effects is developed. The model does not assume that the
      distribution of lesions is Poisson and is applicable to low, intermediate and
      high acute doses of low or high LET radiation. For small doses, the model
      produces the linear-quadratic (LQ) model. However, for high doses the best
      fitting LQ model grossly underestimates cell survival. The same is also true for
      the conventional LQ model, only more so. It is shown that for high doses, the
      microdosimetric distribution can be approximated by a Gaussian distribution, and
      the corresponding cell survival probabilities are compared.

PMID- 20671353
TI  - Dynamic frame selection for in vivo ultrasound temperature estimation during
      radiofrequency ablation.
AB  - Minimally invasive therapies such as radiofrequency ablation have been developed
      to treat cancers of the liver, prostate and kidney without invasive surgery.
      Prior work has demonstrated that ultrasound echo shifts due to temperature
      changes can be utilized to track the temperature distribution in real time. In
      this paper, a motion compensation algorithm is evaluated to reduce the impact of
      cardiac and respiratory motion on ultrasound-based temperature tracking methods.
      The algorithm dynamically selects the next suitable frame given a start frame
      (selected during the exhale or expiration phase where extraneous motion is
      reduced), enabling optimization of the computational time in addition to reducing
      displacement noise artifacts incurred with the estimation of smaller frame-to
      frame displacements at the full frame rate. A region of interest that does not
      undergo ablation is selected in the first frame and the algorithm searches
      through subsequent frames to find a similarly located region of interest in
      subsequent frames, with a high value of the mean normalized cross-correlation
      coefficient value. In conjunction with dynamic frame selection, two different two
      dimensional displacement estimation algorithms namely a block matching and
      multilevel cross-correlation are compared. The multi-level cross-correlation
      method incorporates tracking of the lateral tissue expansion in addition to the
      axial deformation to improve the estimation performance. Our results demonstrate
      the ability of the proposed motion compensation using dynamic frame selection in
      conjunction with the two-dimensional multilevel cross-correlation to track the
      temperature distribution.

PMID- 20671354
TI  - Characterizing the contribution of cardiac and hepatic uptake in dedicated breast
      SPECT using tilted trajectories.
AB  - A small field of view, high resolution gamma camera has been integrated into a
      dedicated breast, single photon emission computed tomography (SPECT) device. The
      detector can be flexibly positioned relative to the breast and image beyond the
      chest wall, allowing the system to capture direct views of the heart and liver.
      The incomplete sampling of these organs creates artifacts in reconstructed
      images, complicating lesion detection. To understand the limits imposed on a 3D
      acquisition trajectory, sequential tilted trajectories at increasing polar tilt
      are utilized to collect data of anthropomorphic phantoms filled with aqueous
      (99m)Tc in a clinically realistic concentration ratio. The counts collected per
      projection between different scans and the SNR, contrast and resolution (FWHM) of
      two hot lesions were compared. As expected, the counts per projection increased
      when the camera had direct views of the heart and liver, but remained relatively
      constant at other angles. The SNR, contrast and FWHM were more affected by the
      insufficient sampling of the data by the large polar angles than by the cardiac
      and hepatic activity. An upper bound on polar tilt for each azimuthal position
      reduces the artifacts in the reconstructed images. Such trajectories were
      implemented to show artifact-free reconstructed images.

PMID- 20671355
TI  - Interactive multiobjective optimization for anatomy-based three-dimensional HDR
      brachytherapy.
AB  - In this paper, we present an anatomy-based three-dimensional dose optimization
      approach for HDR brachytherapy using interactive multiobjective optimization
      (IMOO). In brachytherapy, the goals are to irradiate a tumor without causing
      damage to healthy tissue. These goals are often conflicting, i.e. when one target
      is optimized the other will suffer, and the solution is a compromise between
      them. IMOO is capable of handling multiple and strongly conflicting objectives in
      a convenient way. With the IMOO approach, a treatment planner's knowledge is used
      to direct the optimization process. Thus, the weaknesses of widely used
      optimization techniques (e.g. defining weights, computational burden and trial
      and-error planning) can be avoided, planning times can be shortened and the
      number of solutions to be calculated is small. Further, plan quality can be
      improved by finding advantageous trade-offs between the solutions. In addition,
      our approach offers an easy way to navigate among the obtained Pareto optimal
      solutions (i.e. different treatment plans). When considering a simulation model
      of clinical 3D HDR brachytherapy, the number of variables is significantly
      smaller compared to IMRT, for example. Thus, when solving the model, the CPU time
      is relatively short. This makes it possible to exploit IMOO to solve a 3D HDR
      brachytherapy optimization problem. To demonstrate the advantages of IMOO, two
      clinical examples of optimizing a gynecologic cervix cancer treatment plan are
      presented.

PMID- 20671356
TI  - Parameter variation effects on temperature elevation in a steady-state, one
      dimensional thermal model for millimeter wave exposure of one- and three-layer
      human tissue.
AB  - The present study describes theoretical parametric analysis of the steady-state
      temperature elevation in one-dimensional three-layer (skin, fat and muscle) and
      one-layer (skin only) models due to millimeter-wave exposure. The motivation of
      this fundamental investigation is that some variability of warmth sensation in
      the human skin has been reported. An analytical solution for a bioheat equation
      was derived by using the Laplace transform for the one-dimensional human models.
      Approximate expressions were obtained to investigate the dependence of
      temperature elevation on different thermal and tissue thickness parameters. It
      was shown that the temperature elevation on the body surface decreases
      monotonically with the blood perfusion rate, heat conductivity and heat transfer
      from the body to air. Also revealed were the conditions where maximum and minimum
      surface temperature elevations were observed for different thermal and tissue
      thickness parameters. The surface temperature elevation in the three-layer model
      is 1.3-2.8 times greater than that in the one-layer model. The main reason for
      this difference is attributed to the adiabatic nature of the fat layer. By
      considering the variation range of thermal and tissue thickness parameters which
      causes the maximum and minimum temperature elevations, the dominant parameter
      influencing the surface temperature elevation was found to be the heat transfer
      coefficient between the body surface and air.

PMID- 20671357
TI  - Combining variational and model-based techniques to register PET and MR images in
      hand osteoarthritis.
AB  - Co-registration of clinical images acquired using different imaging modalities
      and equipment is finding increasing use in patient studies. Here we present a
      method for registering high-resolution positron emission tomography (PET) data of
      the hand acquired using high-density avalanche chambers with magnetic resonance
      (MR) images of the finger obtained using a 'microscopy coil'. This allows the
      identification of the anatomical location of the PET radiotracer and thereby
      locates areas of active bone metabolism/'turnover'. Image fusion involving data
      acquired from the hand is demanding because rigid-body transformations cannot be
      employed to accurately register the images. The non-rigid registration technique
      that has been implemented in this study uses a variational approach to maximize
      the mutual information between images acquired using these different imaging
      modalities. A piecewise model of the fingers is employed to ensure that the
      methodology is robust and that it generates an accurate registration. Evaluation
      of the accuracy of the technique is tested using both synthetic data and PET and
      MR images acquired from patients with osteoarthritis. The method outperforms some
      established non-rigid registration techniques and results in a mean registration
      error that is less than approximately 1.5 mm in the vicinity of the finger
      joints.

PMID- 20671358
TI  - Terahertz imaging applied to cancer diagnosis.
AB  - We report on terahertz (THz) time-domain spectroscopy imaging of 10 microm thick
      histological sections. The sections are prepared according to standard
      pathological procedures and deposited on a quartz window for measurements in
      reflection geometry. Simultaneous acquisition of visible images enables
      registration of THz images and thus the use of digital pathology tools to
      investigate the links between the underlying cellular structure and specific THz
      information. An analytic model taking into account the polarization of the THz
      beam, its incidence angle, the beam shift between the reference and sample pulses
      as well as multiple reflections within the sample is employed to determine the
      frequency-dependent complex refractive index. Spectral images are produced
      through segmentation of the extracted refractive index data using clustering
      methods. Comparisons of visible and THz images demonstrate spectral differences
      not only between tumor and healthy tissues but also within tumors. Further
      visualization using principal component analysis suggests different mechanisms as
      to the origin of image contrast.

PMID- 20671359
TI  - In situ doping of ZnO nanowires using aerosol-assisted chemical vapour
      deposition.
AB  - An in situ doping approach of producing Al-doped ZnO NWs was demonstrated using
      an aerosol-assisted chemical vapour deposition (AA-CVD) technique. In this
      technique, Zn precursor was kept in the middle of a horizontal tube furnace
      whereas the dopant solution was kept in an aerosol generator, which was located
      outside the furnace. The Al aerosol was flowed into the reactor during the growth
      of NWs in order to achieve in situ doping. Al-doped ZnO NWs were synthesized as
      verified by the combination of XRD, TEM/EDS and TOF-SIMS analysis. Highly (00.2)
      oriented ZnO seed layers were used to promote vertically aligned growth of Al
      doped ZnO NWs. Lastly, a growth mechanism of vertically aligned Al-doped ZnO NWs
      was discussed.

PMID- 20671360
TI  - Selective phase synthesis of a high luminescence Gd2O3:Eu nanocrystal phosphor
      through direct solution combustion.
AB  - A Gd(2)O(3):Eu nanocrystal phosphor has been directly synthesized by a mild
      solution combustion method with a single step approach while avoiding further
      thermal annealing. The as-combusted Gd(2)O(3):Eu powders have been characterized
      by x-ray diffraction, infrared spectroscopy, transmission electron microscopy and
      photoluminescence spectra. The ratio of citric acid to metal nitrate (C/M) has a
      critical impact on the phase composition and crystallization of as-combusted
      Gd(2)O(3):Eu. An optimal C/M ratio of 0.7 gave highly crystalline powders with a
      single cubic phase, and a high luminescence intensity comparable with that of a
      commercial Y(2)O(3):Eu phosphor, even without further thermal annealing. This
      direct solution combustion method can be used to prepare a variety of high
      quality oxide nanocrystals.

PMID- 20671361
TI  - Hybrid solar cells based on P3HT and Si@MWCNT nanocomposite.
AB  - A nanocomposite material (Si@MWCNT) with a core/sheath heterostructure consisting
      of silicon nanoparticles (Si-NPs) covalently bonded onto a multi-walled carbon
      nanotube (MWCNT) is used as a new material for solar cells. The photovoltaic
      response of a poly (3-hexylthiophene) (P3HT)/Si@MWCNT hybrid film is studied by I
      V measurements under simulated one-sun AM 1.5 illumination (100 mW cm(-2)). In
      comparison with simple P3HT/Si-NPs and P3HT/MWCNT devices, the power conversion
      efficiency of the (P3HT)/Si@MWCNT nano-hybrid device is enhanced by 3 and 20
      times, respectively. Photo-physical and energy diagram investigations suggest
      that the improved device performance is attributed to the combination of
      efficient charge generation by the P3HT/Si-NPs bulk heterojunction and efficient
      charge collection as a result of MWCNT template directed carrier transport.

PMID- 20671362
TI  - Large-scale assembly of 'type-switchable' field effect transistors based on
      carbon nanotubes and nanoparticles.
AB  - We report the large-scale assembly of type-switchable field effect transistors
      (FETs) based on carbon nanotubes (CNTs) and nanoparticles (NPs). In this device,
      the charges stored in NPs adjacent to ambipolar CNT channels were adjusted to
      control the carrier type and density in the channels. We demonstrated the real
      time reconfiguration of individual FET types and logic circuit functionality.
      Theoretical simulation of a model system was provided to explain this doping
      effect. This work takes advantage of the ambipolar properties of CNTs and opens
      up the possibility to build new types of devices with reconfigurable
      functionalities.

PMID- 20671363
TI  - Spin polarization of neutral excitons in quantum dots: the role of the carrier
      collection area.
AB  - A high degree (approximately 55%) of circular polarization has been observed for
      the neutral exciton in InAs/GaAs quantum dots (QDs). The possibility to record
      non-zero polarization of the neutral exciton is explained in terms of different
      capture times of the light electron compared with the heavier holes into the QDs
      from the wetting layer. This interpretation is supported by the progressive
      reduction of the polarization degree with increasing QD density, and also with
      increasing temperature.

PMID- 20671364
TI  - Laser welding of nanoparticulate TiO2 and transparent conducting oxide electrodes
      for highly efficient dye-sensitized solar cell.
AB  - Poor interfacial contact is often encountered in nanoparticulate film-based
      devices. The dye-sensitized solar cell (DSSC) is a representative case in which a
      nanoporous TiO(2) electrode needs to be prepared on the transparent conducting
      oxide (TCO)-coated glass substrate. In this study, we demonstrate that the inter
      electrode contact resistance accounts for a considerable portion of the total
      resistance of a DSSC and its efficiency can be greatly enhanced by welding the
      interface with a laser. TiO(2) films formed on the TCO-coated glass substrate
      were irradiated with a pulsed ultraviolet laser beam at 355 nm; this transmits
      through the TCO and glass but is strongly absorbed by TiO(2). Electron microscopy
      analysis and impedance measurements showed that a thin continuous TiO(2) layer is
      formed at the interface as a result of the local melting of TiO(2) nanoparticles
      and this layer completely bridges the gap between the two electrodes, improving
      the current flow with a reduced contact resistance. We were able to improve the
      efficiency by 35-65% with this process. DSSCs fabricated using a homemade TiO(2)
      paste revealed an efficiency improvement from eta = 3.3% to 5.4%, and an increase
      from 8.2% to 11.2% was achieved with the TiO(2) electrodes made from a commercial
      paste.

PMID- 20671365
TI  - Force-detected nuclear magnetic resonance: recent advances and future challenges.
AB  - We review recent efforts to detect small numbers of nuclear spins using magnetic
      resonance force microscopy. Magnetic resonance force microscopy (MRFM) is a
      scanning probe technique that relies on the mechanical measurement of the weak
      magnetic force between a microscopic magnet and the magnetic moments in a sample.
      Spurred by the recent progress in fabricating ultrasensitive force detectors,
      MRFM has rapidly improved its capability over the last decade. Today it boasts a
      spin sensitivity that surpasses conventional, inductive nuclear magnetic
      resonance detectors by about eight orders of magnitude. In this review we touch
      on the origins of this technique and focus on its recent application to nanoscale
      nuclear spin ensembles, in particular on the imaging of nanoscale objects with a
      three-dimensional (3D) spatial resolution better than 10 nm. We consider the
      experimental advances driving this work and highlight the underlying physical
      principles and limitations of the method. Finally, we discuss the challenges that
      must be met in order to advance the technique towards single nuclear spin
      sensitivity-and perhaps-to 3D microscopy of molecules with atomic resolution.

PMID- 20671366
TI  - Disorder-based graphene spintronics.
AB  - The use of the spin of the electron as the ultimate logic bit-in what has been
      dubbed spintronics-can lead to a novel way of thinking about information flow. At
      the same time single-layer graphene has been the subject of intense research due
      to its potential application in nanoscale electronics. While defects can
      significantly alter the electronic properties of nanoscopic systems, the lack of
      control can lead to seemingly deleterious effects arising from the random
      arrangement of such impurities. Here we demonstrate, using ab initio density
      functional theory and non-equilibrium Green's functions calculations, that it is
      possible to obtain perfect spin selectivity in doped graphene nanoribbons to
      produce a perfect spin filter. We show that initially unpolarized electrons
      entering the system give rise to 100% polarization of the current due to random
      disorder. This effect is explained in terms of different localization lengths for
      each spin channel which leads to a new mechanism for the spin filtering effect
      that is disorder-driven.

PMID- 20671369
TI  - Transcatheter aortic valve implantation in high-risk patients with severe aortic
      stenosis.
AB  - Although surgery is the gold standard for severe aortic stenosis (AS) treatment,
      it is considered high risk in elderly patients because of high complication
      rates, which leads to substantial hesitation in submitting such patients to
      surgery. With the growing need to treat elderly patients with severe AS,
      percutaneous transcatheter aortic valve implantation (TAVI) was pioneered in
      2001, followed by implantation of a self-expanding percutaneous aortic valve in
      2005. As of April 2010, these 2 methods of TAVI have been used in more than
      15,000 patients throughout the world. The acute success rate of this procedure is
      now increasing up to 95.4% by the transfemoral approach and 92.7% by the
      transapical approach with regard to Edwards SAPIEN valve implantation. In terms
      of the Corevalve ReValving system, it is reported as 98.2% in an expert's hands.
      This article reviews the methods of TAVI and the devices, not yet been approved
      in Japan but are expected to be available in a few years.

PMID- 20671370
TI  - Heparin cofactor II attenuates vascular remodeling in humans and mice.
AB  - Heparin cofactor II (HCII), a serine protease inhibitor (serpin), inactivates
      thrombin action in the subendothelial layer of the vascular wall. Because a
      congenitally HCII-deficient patient has been shown to have multiple
      atherosclerotic lesions, it is hypothesized that HCII plays a pivotal role in the
      development of vascular remodeling, including atherosclerosis. To clarify this
      issue, 3 clinical studies concerning plasma HCII activity and atherosclerosis
      were carried out, and results demonstrated that a higher incidence of in-stent
      restenosis after percutaneous coronary intervention, maximum carotid arterial
      plaque thickness, and prevalence of peripheral arterial disease occurred in
      subjects with low plasma HCII activity. Furthermore, HCII-deficient mice were
      generated by a gene targeting method to determine the mechanism of the vascular
      protective action of HCII. Because HCII(-/-) mice were embryonically lethal, we
      used HCII(+/-) mice and found that they manifested augmentation of intimal
      hyperplasia and increased thrombosis after cuff or wire injury to the femoral
      arteries. HCII(+/-) mice with vascular injury showed augmentation of inflammatory
      cytokines and chemokines and oxidative stress. These abnormal phenotypes of
      vascular remodeling observed in HCII(+/-) mice were almost restored by human HCII
      protein supplementation. HCII protects against vascular remodeling, including
      atherosclerosis, in both humans and mice, and plasma HCII activity might be a
      predictive biomarker and novel therapeutic target for the prevention of
      cardiovascular diseases.

PMID- 20671371
TI  - Clinical significance of intensive lipid-lowering therapy using statins in
      patients with coronary artery disease: LDL-cholesterol: the lower, the better; is
      it true for Asians? (Pro).
AB  - Large clinical trials have elucidated that lipid-lowering therapy using statins
      reduces cardiovascular events in patients with coronary artery disease (CAD). The
      benefit of statin therapy is proportional to the achieved low-density lipoprotein
      cholesterol level (LDL-C) up to 70 mg/dl. On the basis of this evidence, the
      American Heart Association and American College of Cardiology offer an optimal
      LDL-C goal of <70 mg/dl for patients with a very high risk of CAD. In addition,
      with regard to acute coronary syndrome (ACS), which has a high risk for future
      cardiac events because of the presence of vulnerable plaque, intensive lipid
      lowering therapy from the early stage is the standard treatment. On the other
      hand, the mechanism of inhibition of cardiac events by statins is thought to be
      predominantly based on stabilization of plaque, but research on the role of
      plaque regression is also advancing. The clinical significance of intensive lipid
      lowering therapy using statins will be discussed from the following standpoints:
      (1) large-scale clinical trials around the world; (2) the relationship with
      plaque regression and stabilization; (3) the relationship with the diverse
      effects of statins; and (4) evidence generated from Japanese patients.

PMID- 20671372
TI  - "Just make it lower" is an alternative strategy of lipid-lowering therapy with
      statins in Japanese patients: LDL-cholesterol: the lower, the better; is it true
      for Asians? (Con).
AB  - It is well known that statins improve the prognosis of cardiovascular diseases
      (CVD). Recent randomized control trials (RCTs) of statins conducted in Western
      countries revealed greater avoidance of cardiovascular events if low-density
      lipoprotein cholesterol (LDL-C) reached lower levels. However, it is obvious that
      this evidence cannot be unconditionally extrapolated to Asians because there are
      great differences between Japanese and Caucasians in the absolute onset rate of
      CVD. Results of RCTs with Japanese for primary or secondary prevention of
      cardiovascular events indicate that we could benefit from statins with a
      relatively higher target LDL-C as compared with Western populations. In this
      situation, not only strong but also standard statins are still advantageous and
      the so-called pleiotropic effects of the drugs come to the fore. In this review,
      we first discuss differences in the absolute event rate in different populations,
      and then the lack of evidence for recommended LDL-C treatment targets,
      particularly in Japanese, although there is reliable evidence for reductions in
      plaque volume in coronary arteries from RCTs recently conducted in Japan with
      aggressive lipid-lowering therapy with strong statins. Finally, based on recent
      data, we propose a new concept regarding the secondary prevention of CVD for
      current Japanese populations.

PMID- 20671373
TI  - Guidelines for diagnosis and treatment of patients with vasospastic angina
      (coronary spastic angina) (JCS 2008): digest version.

PMID- 20671374
TI  - Self-administered questionnaire is a reliable measure of coffee consumption.
AB  - BACKGROUND: The objective of this study was to assess the agreement and
      repeatability of 2 methods of measuring habitual coffee consumption, and to
      examine their homogeneity with respect to socioeconomic and lifestyle factors.
      METHODS: Data on coffee consumption were collected from 4254 subjects by means of
      a health questionnaire (HQ) and a 1-year dietary history interview (DHI), the
      latter of which was used as the reference method during the Finnish Mobile Clinic
      Health Examination Survey conducted in 1973-1976. Short-term repeatability of the
      methods was assessed using data from 286 and 93 subjects who repeated the HQ and
      the DHI, respectively, after an interval of 4 to 8 months. The strength of
      agreement between the 2 methods and between the repeated measurements was
      estimated using intraclass correlation coefficients (ICCs). RESULTS: The ICC was
      0.86 for the agreement between the HQ and the DHI, and 0.77 and 0.85 for the
      repeatability of the HQ and the DHI, respectively. There were no statistically
      significant systematic differences in mean intake values between the 2 methods or
      between repeated measurements. In subgroup analysis of background variables,
      there were only minor differences in agreement and repeatability, with somewhat
      higher ICC values among subjects with a healthier lifestyle and higher education.
      CONCLUSIONS: The high reliability and homogeneity of the health questionnaire
      make it a useful tool for measuring habitual coffee consumption for the purposes
      of epidemiological research.

PMID- 20671375
TI  - Prevalence of the equol-producer phenotype and its relationship with dietary
      isoflavone and serum lipids in healthy Chinese adults.
AB  - BACKGROUND: Studies have suggested that daidzein-metabolizing phenotypes have
      beneficial effects on a range of health outcomes. We investigated the prevalence
      of equol producers and the relationship of equol phenotype with habitual
      isoflavone consumption and serum lipid concentrations in 200 Chinese adults in
      Beijing. METHODS: After the baseline survey and dietary records, 200 healthy
      adults in Beijing were challenged with a soy-isoflavone supplement for 3 days; 24
      hour urine samples were collected before and after the challenge. Isoflavones and
      their metabolites in urine were measured to determine equol phenotype. Serum
      lipids, uric acid, and other biochemical markers were also measured. RESULTS:
      Only 26.8% of the participants excreted equol when on a regular diet, as compared
      with 60.4% after the challenge. After the challenge, urinary isoflavonoid
      excretion increased in all participants, while equol excretion increased only in
      equol producers. Isoflavone intake was correlated with urinary isoflavone (range
      r = 0.49-0.58, P < 0.01). As compared with nonproducers, equol producers were
      less likely to consume cereals (P < 0.001). There was no significant correlation
      between serum lipids and isoflavone intake. Serum lipids were not significantly
      affected by equol phenotype. CONCLUSIONS: Urinary equol excretion was detected in
      about 25% of participants under their usual dietary conditions. Their potential
      to produce equol was increased after the challenge. Urinary isoflavone levels may
      serve as a useful biomarker for isoflavone intake in populations. We observed an
      association between equol phenotype and cereal intake. Our findings also suggest
      that dietary isoflavone intake has no significant effect on serum lipids in
      healthy participants, regardless of equol phenotype.

PMID- 20671376
TI  - Cilostazol may suppress restenosis and new contralateral carotid artery stenosis
      after carotid endarterectomy.
AB  - Carotid artery restenosis is a serious complication following carotid
      endarterectomy (CEA), so preventative management of the risk factors is
      important. The present study investigated the potential of cilostazol, a mediator
      of vascular stabilization as well as inhibitor of platelet aggregation, to
      suppress restenosis on the ipsilateral carotid artery and new plaque development
      on the contralateral carotid artery. Eighty-two patients treated by CEA were
      divided into two groups according to the postoperative antiplatelet aggregation
      drugs into the cilostazol and other groups. Patients were periodically examined
      for recurrence of the plaque on the ipsilateral side, development of plaque on
      the contralateral side, and the bilateral intermedia thicknesses measured by
      ultrasonographic examination for up to 6 years. Restenosis and development of the
      contralateral plaque were not detected in any patients in the cilostazol group,
      whereas such changes were found in seven patients in the other group. Cilostazol
      might be effective to inhibit the growth mechanism of plaque.

PMID- 20671377
TI  - Problems with diagnosis by fluid-attenuated inversion recovery magnetic resonance
      imaging in patients with acute aneurysmal subarachnoid hemorrhage.
AB  - The diagnostic efficacy of fluid-attenuated inversion recovery (FLAIR) magnetic
      resonance imaging and computed tomography (CT) for acute subarachnoid hemorrhage
      (SAH) were compared and the problems with diagnosis were investigated in 81
      patients with aneurysmal SAH within 24 hours after onset who underwent FLAIR
      imaging and CT on admission. The number of hematomas in the cisterns and
      ventricles were evaluated by clot scores. In addition, the frequency of
      undetected hematomas was calculated for the cisterns and ventricles. Clot scores
      were significantly higher for FLAIR imaging than for CT in the lateral sylvian,
      quadrigeminal, and convexity cisterns. On the other hand, clot scores were
      significantly higher for CT than for FLAIR imaging in the interhemispheric and
      medial sylvian cisterns. The overall frequency of undetected SAH was 2% for FLAIR
      imaging and 14% for CT. With the exception of the interhemispheric and medial
      sylvian cisterns, the frequency of undetected SAH was higher for CT than for
      FLAIR imaging. In this study, FLAIR imaging was more sensitive than CT for the
      detection of acute SAH within 24 hours after onset. However, the diagnostic
      efficacy of FLAIR imaging was reduced in comparatively tight cisterns.

PMID- 20671378
TI  - Effects and complications of stereotactic aspiration for spontaneous
      intracerebral hemorrhage.
AB  - Stereotactic aspiration of intracerebral hemorrhage (ICH) improves the general
      condition of patients, promotes improvement of consciousness, and decreases the
      incidence of pneumonia, but may induce rebleeding. The present study investigated
      the effects of stereotactic aspiration and factors that inhibit rebleeding in 70
      consecutive patients who underwent stereotactic aspiration for ICH. Consciousness
      was significantly improved after surgery. Of patients who underwent surgery on
      day 0 or 1, 5 patients developed pneumonia and 29 patients did not. Of patients
      who underwent surgery on day 2 or later, 14 patients developed pneumonia and 22
      patients did not. Early surgery within 2 days significantly reduced the rate of
      aspiration pneumonia. Patients with rebleeding tended to have liver dysfunction
      and hemorrhagic tendency. Early stereotactic aspiration of ICH facilitates better
      patient management than conservative treatment in patients with moderate
      consciousness disturbance. Patients with liver dysfunction and hemorrhagic
      tendency should be identified.

PMID- 20671379
TI  - Bystander killing effect of tymidine kinase gene-transduced adult bone marrow
      stromal cells with ganciclovir on malignant glioma cells.
AB  - Transduction of the suicide gene of Herpes simplex virus thymidine kinase (Hsv
      tk) into glioma cells or neural stem cells combined with pro-drug ganciclovir
      (GCV) treatment has been effective to treat experimental glioma in the rat
      through the bystander effect. Bone marrow stromal cells (MSCs) in the adult bone
      marrow have tropism for brain tumors and act as tumor stromal cells. Whether
      adult MSCs expressing Hsv-tk can also act as effector cells of the bystander
      killing effect on murine glioma cells was investigated. In vitro study of co
      culture between 9L/LacZ (9L) glioma cells and Hsv-tk-transduced MSCs (MSCs/tk(+))
      followed by GCV administration in the culture medium resulted in apparent nuclear
      morphological changes in the 9L glioma cells surrounding the MSCs/tk(+). 9L
      glioma cell survival in the presence of MSCs/tk(+) and GCV treatment was
      quantitatively measured and showed significant decrease of 9L glioma cell
      proliferation with higher MSCs/tk(+) ratio and GCV concentration. Intracerebral
      co-inoculation experiments in Fisher rats used 9L glioma cells and either
      MSCs/tk(+) or Hsv-tk-non-transduced MSCs (MSCs/tk(-)) followed by intraperitoneal
      injection of GCV (100 mg/kg, daily for 7 days). The animals co-inoculated with 9L
      glioma cells and MSCs/tk(+) showed significant retardation of tumor growth and
      prolongation of survival time compared with the animals with 9L glioma cells and
      MSCs/tk(-). Quantitative findings were established of the novel effects of adult
      MSCs/tk(+) as effector cells of the bystander killing effect on glioma cells.

PMID- 20671380
TI  - Neuropsychological improvement in patients with cervical spondylotic myelopathy
      after posterior decompression surgery.
AB  - Patients with cervical spondylotic myelopathy sometimes complain of cognitive
      dysfunction, which may be coincidence. However, cognitive dysfunction may be
      related to disorders of the cervical spine and/or spinal cord. This study
      investigated cognitive dysfunction in patients with cervical spinal disorders. A
      total of 79 patients with cervical spondylotic myelopathy (40 women and 39 men,
      mean age 61.2 years) underwent cervical laminoplasty between January 2006 and
      July 2007. Ten of these 79 patients (7 women and 3 men, mean age 65.2 years)
      complained of moderate to severe memory disturbances. These 10 patients underwent
      neuroimaging studies and a battery of neuropsychological tests consisting of the
      mini-mental state examination, Kohs Block Design Test, Miyake Memory Test, Benton
      Visual Retention Test (BVRT), and "kana-hiroi" test before and 3 months after
      surgery. Brain magnetic resonance imaging showed no organic brain lesions in the
      10 patients, but single photon emission computed tomography demonstrated reduced
      regional cerebral blood flow in the posterior cortical areas in eight patients
      before surgery. Neuropsychological test scores showed statistically significant
      improvement after surgery in the Kohs Block Design Test and the BVRT, which
      measure visuospatial perception and reflect the function of the parietal and/or
      occipital lobes (p < 0.05). The practice effect may have contributed to the
      neuropsychological improvements, but this study suggests that cervical spinal
      disorders may affect cognitive functions and that surgical treatment can
      ameliorate such effects.

PMID- 20671381
TI  - Comparative analysis of spinal hemangioblastomas in sporadic disease and Von
      Hippel-Lindau syndrome.
AB  - The clinical differences were evaluated in spinal hemangioblastoma between
      patients with sporadic disease and patients with von Hippel-Lindau (VHL)
      syndrome. The distribution of hemangioblastomas in the central nervous system was
      investigated in 56 patients treated between 1988 and 2008 at the University of
      Tokyo Hospital. The characteristics of spinal hemangioblastomas were compared in
      35 patients including 17 with sporadic disease and 18 with VHL syndrome treated
      between 1988 and 2008 at our hospital and three affiliated institutions. Spinal
      hemangioblastomas were much more prevalent in patients with VHL syndrome (88.2%)
      than in patients with sporadic disease (20.5%, p < 0.001). Spinal
      hemangioblastomas associated with VHL syndrome were diagnosed a decade earlier (p
      = 0.007) and were associated with less severe neurological symptoms than sporadic
      lesions (p = 0.004). Most patients with sporadic disease had a single lesion at
      the cervical or thoracic level, whereas patients with VHL syndrome had multiple
      lesions at all spinal levels (p = 0.04). Patients with sporadic disease exhibited
      significant improvement in postoperative neurological status (p = 0.02), whereas
      patients with VHL syndrome had no change in status (p = 1.00). Number of removed
      lesions (p = 0.03) and lower spinal cord lesions (p = 0.05) were associated with
      poor surgical outcome. Tumor recurrence was correlated with partial removal of
      lesions (p = 0.05). One third of patients with VHL syndrome developed new lesions
      every 2 years. The major finding of this study is that the incidence of spinal
      hemangioblastoma, distributed through all spinal levels, may be as high as 88% in
      patients with VHL syndrome, which is much greater than previously reported.

PMID- 20671382
TI  - Fusiform aneurysm associated with fenestration of the posterior communicating
      artery.
AB  - A 62-year-old male presented with a rare case of fenestration of the supraclinoid
      segment of the internal carotid artery (ICA) at the origin of the posterior
      communicating artery (PCoA). The patient had a fusiform aneurysm at the proximal
      branch of the PCoA, which was successfully clipped, sparing the anterograde blood
      flow. The double origin and fenestration of the PCoA branching off at the C(2)
      segment of the left ICA suggested that this anomalous fenestration might have
      developed as the origin of the PCoA rather than the supraclinoid ICA during the
      early embryonal stage.

PMID- 20671383
TI  - Compression of the medulla oblongata and acute respiratory failure caused by
      rupture of a thrombosed large aneurysm of the anterior inferior cerebellar
      artery.
AB  - A 65-year-old female presented with an extremely rare case of a ruptured
      thrombosed large aneurysm of the anterior inferior cerebellar artery (AICA) in
      which a local hematoma compressed the medulla oblongata and caused acute
      respiratory failure. She first presented with dizziness, general fatigue, and
      nausea 2 months before admission. She was hospitalized for intense general
      fatigue, nausea, and occipitalgia. Computed tomography and T(1)-weighted magnetic
      resonance imaging showed a heterogeneous lesion around the right cerebello
      medullary cistern. Angiography revealed a fusiform aneurysm of the right AICA.
      Asphyxia occurred 4 days after admission and the patient underwent an emergency
      operation. No subarachnoid hematoma was present, but a hematoma around the
      ruptured portion markedly compressed the medulla oblongata. The medulla oblongata
      was adequately decompressed after subtotal removal of the aneurysm. The patient's
      respiratory status and consciousness level recovered after the operation.

PMID- 20671384
TI  - Simultaneous occurrence of subarachnoid hemorrhage and cerebral infarction caused
      by anterior cerebral artery dissection treated by endovascular trapping.
AB  - A 48-year-old man presented with a rare dissection of the anterior cerebral
      artery (ACA) causing simultaneous subarachnoid hemorrhage (SAH) and cerebral
      infarction manifesting as sudden onset of headache and left hemiparesis. Computed
      tomography and magnetic resonance imaging showed SAH localized in the
      interhemispheric fissure and cerebral infarction in the territory of the right
      ACA. Digital subtraction angiography (DSA) demonstrated segmental narrowing and
      dilatation at the right A(1) and A(2) portions of the ACA, leading to a diagnosis
      of ACA dissection. Fourteen days after the onset, DSA confirmed the enlarged
      fusiform dilatation of the right A(2) portion with distal narrowing, suggesting
      the risk of rerupture of the dissection. Endovascular obliteration of the
      aneurysm with parent artery occlusion was performed without anastomosis on day
      16. The aneurysm was catheterized and obliterated with detachable coils.
      Postoperative DSA revealed complete obliteration of the dissection and parent
      artery. The patient was doing well without recurrence of the dissection 8 months
      after the intervention. The simultaneous occurrence of SAH and cerebral
      infarction in patients with ACA dissection is extremely rare, and the optimal
      treatment has not yet been established. Endovascular treatment is safe and
      effective for the treatment of ACA dissection.

PMID- 20671385
TI  - Ruptured pseudoaneurysm of the petrous internal carotid artery caused by chronic
      otitis media.
AB  - A 60-year-old man presented with a rare case of pseudoaneurysm in the petrous
      internal carotid artery (ICA) caused by chronic otitis media manifesting as right
      otorrhagia after the earpick procedure. Computed tomography showed the destroyed
      petrous bone; the ICA and the aneurysm, which were exposed to the right middle
      ear; and a massive hematoma in the right middle ear. Right carotid angiography
      revealed a pseudoaneurysm arising from the ICA coursing through the middle ear.
      Two weeks later, the right ICA was trapped after external carotid artery-middle
      cerebral artery bypass surgery using a vein graft. A biopsy specimen was obtained
      from the middle ear and the histological diagnosis was inflammatory disease.
      Pseudoaneurysm often causes sudden massive aural bleeding. The appropriate
      management strategy may be exclusion of the pseudoaneurysm with revascularization
      to avoid leaving foreign material in the infected middle ear.

PMID- 20671386
TI  - Unusual delayed hydrocephalus after bare platinum coil embolization of an
      unruptured aneurysm.
AB  - A 69-year-old woman developed hydrocephalus after the embolization of an
      incidentally detected unruptured large internal carotid artery aneurysm with bare
      platinum coils. Endovascular embolization resulted in near-total aneurysm
      occlusion. She complained of mild headache 18 hours after the procedure and
      magnetic resonance (MR) imaging performed on the 6(th) post-treatment day
      revealed wall enhancement and perianeurysmal brain edema. Follow-up MR imaging
      showed recanalization of the aneurysm and gradual ventricular enlargement. She
      presented with typical symptoms of hydrocephalus including disorientation, gait
      disturbance, and urine incontinence at 7 months post-embolization. We removed 30
      ml of cerebrospinal fluid by lumbar tap, which improved her condition without
      symptom recurrence for 2 months. She did not require shunt placement. Post
      interventional hydrocephalus is known in patients with unruptured aneurysms
      embolized with bioactive second-generation coils. This case shows that
      hydrocephalus can occur after aneurysm embolization with bare platinum coils
      without intracranial hemorrhage.

PMID- 20671387
TI  - Meningioma manifesting as cerebral infarction.
AB  - A previously healthy 31-year-old man presented with an extremely rare case of
      small meningioma associated with cerebral infarction preceded by recurrent
      transient ischemic attacks manifesting as a 3-day history of recurrent and
      transient weakness of the left lower limb lasting several minutes for each
      episode. The symptoms became persistent and complete on the following day.
      Magnetic resonance imaging revealed acute cerebral infarction in the right
      frontal lobe and a 20 mm diameter tumor in the planum sphenoidale encasing the
      right anterior cerebral artery. Cerebral angiography demonstrated occlusion of
      the right A(2) portion. The patient underwent surgery and the tumor was gross
      totally removed. The histological diagnosis was meningothelial meningioma. Cases
      of meningioma causing cerebral infarction are very rare, but the possibility
      should be considered even if the tumor is small.

PMID- 20671388
TI  - Germinoma with syncytiotrophoblastic giant cells arising in the corpus callosum.
AB  - A previously healthy 31-year-old Japanese man presented with a very rare
      germinoma of the corpus callosum without other intracranial lesions manifesting
      as transitory speech disturbance. Magnetic resonance (MR) imaging revealed a
      heterogeneously enhanced mass in the corpus callosum extending into the cavity of
      the septum pellucidum. A tumor specimen obtained by stereotactic biopsy revealed
      a two-cell pattern germinoma containing human chorionic gonadotropin (HCG)-beta
      positive giant cells. The cerebrospinal fluid and serum levels of HCG and HCG
      beta subunit were measurable. The diagnosis was germinoma with
      syncytiotrophoblastic giant cells. Three cycles of chemotherapy consisting of
      ifosfamide, cisplatin, and etoposide, followed by radiation therapy achieved
      complete remission, and 5 cycles of chemotherapy with carboplatin and etoposide
      were added. MR imaging performed 40 months after the diagnosis showed a
      cicatricial cyst in the body of the corpus callosum, the original tumor site. All
      11 previously reported cases of germinoma in the corpus callosum were associated
      with synchronous or metachronous intracranial lesions. These patients tended to
      be older than patients with general intracranial germinoma. Germinoma should be
      included in the differential diagnosis of corpus callosum tumors, especially in
      young adult males.

PMID- 20671389
TI  - Primary intramedullary spinal cord germinoma.
AB  - A 21-year-old woman presented with an intramedullary spinal cord germinoma and a
      history of gait disturbance and elimination disorder. Magnetic resonance (MR)
      imaging demonstrated two isolated lesions, one located within the medulla between
      T9 and T11, and another at the cauda equina (L2 to L3 levels). After partial
      reduction of the intramedullary mass, histological findings revealed that the
      tumor was typical germinoma. Further MR imaging revealed no evidence of
      intracranial germinoma. Combined chemotherapy (carboplatin and etoposide) and
      whole spine radiation were performed. Follow-up MR imaging showed that the
      enhanced mass at the L2-L3 levels had disappeared. No recurrence of the tumor has
      been detected 3 years after the operation, and no dissemination into the cranial
      area was detected. Cisplatin and etoposide chemotherapy combined with
      radiotherapy is recommended for primary spinal germinoma, and is effective for
      inhibition of both tumor dissemination and recurrence.

PMID- 20671390
TI  - Primary diffuse large B-cell lymphomas of the temporoparietal dura mater and
      scalp without intervening skull bone invasion.
AB  - A 72-year-old man presented with an extremely rare case of primary diffuse large
      B-cell lymphomas (DLBCLs) of the dura and scalp existing independently without
      intervening cranial vault invasion. The patient presented with an indolent mass
      lesion at the left temporal parietal scalp. Magnetic resonance imaging and
      computed tomography revealed a solid homogeneously enhanced mass in the left
      temporoparietal scalp, and an extra-axial intracranial mass that existed just
      below the scalp without intervening skull invasion. The patient underwent gross
      total resection of these lesions via a left frontotemporoparietal craniotomy.
      Histological examination of the masses revealed DLBCLs. The patient received
      whole-brain radiation therapy, and subsequent chemotherapy with cyclophosphamide,
      adriamycin, vincristine, and prednisolone. He was discharged without neurological
      deficit. The present case of DLBCLs in the scalp and dura without intervening
      skull bone invasion indicates that malignant lymphoma should be considered in the
      differential diagnosis of scalp and dural tumors without intervening skull bone
      invasion.

PMID- 20671391
TI  - Malignant transformation of craniopharyngioma associated with moyamoya syndrome.
AB  - A 32-year-old man presented with malignant craniopharyngioma associated with
      moyamoya syndrome manifesting as right visual disturbance. Magnetic resonance
      (MR) imaging revealed a parasellar mass lesion diagnosed as adamantinomatous
      craniopharyngioma. He underwent three surgical procedures and repeated courses of
      radiotherapy, and was able to resume his daily life. MR imaging demonstrated
      tumor regrowth and bilateral occlusions of the internal carotid arteries (ICAs)
      with basal moyamoya phenomenon, which might have been induced by irradiation
      and/or tumor compression, 10 years after the initial manifestations. Sufficient
      debulking was safely achieved via the transsphenoidal route and histological
      examination revealed squamous cell carcinoma, indicating malignant transformation
      of craniopharyngioma. The tumor relapsed after only one month, so transsphenoidal
      tumor debulking was tried again. However, the postoperative course was
      unfavorable because of intraoperative bleeding from the right ICA. Malignant
      transformation of craniopharyngioma may be included in moyamoya syndrome. The
      treatment strategy should be carefully considered in such a complicated
      situation.

PMID- 20671392
TI  - Motor cortex stimulation for intractable neuropathic facial pain related to
      multiple sclerosis.
AB  - A 33-year-old man presented with ongoing severe right facial pain and sensory
      disturbances caused by multiple sclerosis (MS). Neuroimaging demonstrated
      demyelinating lesions in the right dorsal pons and medulla oblongata. The pain
      was refractory to carbamazepine at 800 mg/day, gabapentin at 1800 mg/day,
      morphine at 30 mg/day, amitriptyline at 60 mg/day, and diazepam at 4 mg/day,
      along with twice-monthly ketamine (60 mg) drip infusions. The patient underwent
      motor cortex stimulation (MCS), resulting in >60% pain relief, reduction in the
      required doses of pain medications, and discontinuation of ketamine
      administration. MCS is effective for MS-related neuropathic facial pain.

PMID- 20671393
TI  - Allergic reaction following arachnoid plasty with a fibrin sealant.
AB  - A 65-year-old woman underwent surgical treatment of an unruptured aneurysm in the
      left middle cerebral artery. Surgical craniotomy using arachnoid plasty with a
      fibrin sealant was completed without incident, but abrupt neurological
      deterioration occurred on the 9th postoperative day. Antibiotic treatment was
      given, but the symptoms did not resolve. Neuroimaging and physical findings
      indicated allergic reaction rather than infectious process. Therefore, systemic
      steroids were administered that resulted in dramatic resolution of symptoms. Nine
      months later, lymphocyte stimulation test of materials used in arachnoid plasty
      revealed positive response to a component of the combination pair in fibrin glue.
      The fibrin sealant placement method is a widely accepted and familiar technique,
      but surgeons should anticipate possible allergic reactions such as those observed
      in the present case.

PMID- 20671394
TI  - Depth-adjustable fixation of external ventricular drains to counteract
      obstruction in tight ventricles.
AB  - Tightness of the lateral ventricle may result in mechanical obstruction of an
      external ventricular drain (EVD). We propose a modified EVD fixation method that
      allows retraction of the EVD to reopen the drainage. We used this technique in
      patients requiring long-term EVD placement in the frontal horn who were expected
      to develop tightening of the ventricle. We placed a catheter fixation device
      consisting of a dialysis catheter with a catheter-holding wing and a fixture
      spring. The wing is placed on the EVD just distal to its exit and tied down, and
      the fixture spring is attached to the wing to secure the EVD. If EVD obstruction
      associated with tightening of the ventricle was suspected, we removed the spring
      and retracted the EVD to the depth required for cerebrospinal fluid drainage,
      then replaced the spring. Retraction by 5-12 mm (mean 8.7 mm) resulted in opening
      of 8 of the 10 obstructed EVD devices. We encountered no major procedure-related
      complications. This modified EVD fixation method facilitates depth adjustments
      for reopening the obstructed drain.

PMID- 20671395
TI  - Preventive stitching for migration of a peritoneal catheter into the abdominal
      wall after ventriculoperitoneal shunting.
AB  - Migration of the distal end of a ventriculoperitoneal shunt into the abdominal
      wall (epi-peritoneal layer) is a complication which is especially likely in obese
      patients with high intra-abdominal pressure and wide dead space around the
      catheter remaining after laparotomy. A preventive abdominal stitching method for
      this complication was developed consisting of sutures beside the catheter
      penetrating the peritoneum, posterior and anterior sheath of rectus abdominis
      muscle, and subcutaneous fat. This method was applied to more than 20 patients
      who underwent ventriculoperitoneal shunting. No patient experienced shunt
      migration. The technique is easy and safe to perform, avoids leaving a dead space
      around the peritoneal catheter, and prevents catheter migration.

PMID- 20671396
TI  - The exudate of pressure ulcers contains a substantial amount of vascular
      endothelial growth factor.
AB  - Pressure ulcers (PUs) are chronic wounds that occur as areas of tissue necrosis
      that results from external physical compression, shear forces, and friction.
      Recently, the efficacy of polyvinylidene film dressing (PVFD) for PUs without any
      agents promoting wound healing has been reported, suggesting that PUs have their
      own mechanism of spontaneous healing achieved by vascularization, synthesis of
      extracellular matrix, and re-epithelization. Since vascular endothelial growth
      factor (VEGF) 165 and fibroblast growth factor 2 (FGF-2) are released at
      traumatic or surgical wound sites and play major roles in vascularization and
      wound healing, we measured the concentrations of VEGF165 and FGF-2 in the exudate
      and fibrinous sloughs of PUs after PVFD. We collected 10 exudate samples and 3
      samples of fibrinous sloughs from 10 PUs of 9 patients immediately after PVFD for
      8 h and measured VEGF165 and FGF-2 by ELISA. All 10 exudate samples contained
      substantial amounts of VEGF165, from 2.79 to 13.27 microg g(-1), irrespective of
      the severity of the PUs. In contrast, we detected FGF-2 (0.21 and 2.03 microg g(
      1)) in only two exudate samples. Similarly, we detected VEGF165 (from 3.14 to
      5.93 microg g(-1)) and FGF-2 (less than 0.31 microg g(-1)) in fibrinous sloughs
      of 3 PUs. These results demonstrate that the exudate and fibrinous sloughs of PUs
      contain considerable amounts of VEGF, which would contribute to the spontaneous
      healing of PUs by PVFD. The presence of VEGF165 in the exudate of PUs inspires us
      to reconsider the treatment strategy of PUs that enhances the spontaneous
      healing.

PMID- 20671397
TI  - [Trends in research on the history of medicine in Korea before the modern era].
AB  - Research on the history of medicine in Korea in the form of modern scholarship
      began with the publication in 1930 of Yi Neunghwa's "A History of the Development
      of Medicine in Korea." The purpose of the present study lies in surveying studies
      on the history of medicine in Korea in the past 80 years since the publication of
      Yi's paper. In terms of periodization, research on the history of medicine in
      Korea is bifurcated by the publication of two comprehensive histories-i. e., Miki
      Sakae's A History of Medicine and Disease in Korea (1963) and Kim Du-jong's The
      Complete History of Medicine in Korea (1966). Indeed, all earlier studies
      converged in these two books. Because Miki and Kim both had majored in Western
      medicine and conducted research based on similar perspectives, data, and methods,
      the two works overlap considerably, and Kim's book, as the later of the two,
      unfortunately lost the initiative to the former to a considerable extent. As a
      result of these two scholars' research, it became possible to trace the overall
      flow of the history of medicine in Korea. Following the publication of works by
      Miki and Kim and with the advent of the 1980's, research on the history of
      medicine in premodern Korea was renovated with the emergence of no fewer than
      some dozen new doctoral degree holders in the field. In fact, these young
      scholars went beyond surveying trends in each era to expand the scope of specific
      discussions and topics per era, to delve into the actual contents, and to
      elucidate the function of medicine in society. The fruits of studies conducted in
      the past 80 years on the history of medicine in premodern Korea can be summarized
      as follows. 1) before the 5th century AD: the existence of a comprehensive
      medical practice in regions inhabited by those considered to be the ancestors of
      the Korean people; and information on medication including ginseng. 2) 5th-10th
      centuries: the existence of professional medical posts; the management of
      medicine by the royal household; institutions for medical education; the import
      and use of Chinese medical texts; the compilation of independent medical texts;
      the transmission of medical knowledge to Japan; and the import and export of
      medicinal ingredients. 3) 10th-14th centuries: public medical organs; medicine
      focusing on domestic medication; the invitation of medical doctors and the
      transmission of new medicine from Song China; the inclusion of medicine in the
      civil service examinations; the compilation of diverse types of Korean medical
      texts including those on native medicinal ingredients; disaster relief organs;
      regional medical organs; regional medicinal ingredient tribute system; and the
      state's measures against infectious diseases. 4) 14th-17th centuries: the
      consolidation of traditional East Asian medicine; the consolidation of Korean
      medicine including native medicinal ingredients; the emergence of a medical
      tradition that stresses the Daoist preservation of health ; and the publication
      of dozens of types of Chinese and Korean medical texts led by the entral and
      regional governments. Also noteworthy is the emergence of simple medical texts on
      emergency relief, pregnancy and childbirth, smallpox, and epidemics ( as well as
      the dissemination of their vernacular editions. In addition, there were phenomena
      such as the increasing occupation of the posts of medical officials by the non
      aristocratic middling jung'in class; the existence of Confucian scholar
      physicians and women physicians; and the compilation of texts on independent
      external medicine. 5) 17th-19th centuries: the formation of medicinal ingredient
      markets; the spread of pharmacies throughout the provinces; a vogue for Ming
      Chinese medical texts; veneration for the Treasured Mirror of Eastern Medicine;
      the emergence of a positivistic stance toward medical research; a vogue for
      experiential remedies; interest in Western medicine; compilation of several
      medical texts on measles; criticism of Chinese traditional medicine and/or Korean
      traditional medicine; the spread of variolation; attempts to introduce smallpox
      vaccination ; Korean-Japanese medical exchange through the dispatch of Korean
      goodwill missions to Japan; a great vogue for the Treasured Mirror of Eastern
      Medicine in both China and Japan; the emergence of independent medical texts on
      acupuncture; the successful cultivation and massive export of ginseng; and the
      birth of the Sasang (4-type) constitutional typology, a native medical tradition.

PMID- 20671398
TI  - [The trend and prospect of studies in the modern history of medicine in Korea].
AB  - The Korean Journal of Medical History published in 1992 provides spaces for
      publication to medical historians who have been growing increasingly since the
      1990s, thereby stimulating studies in the modern history of medicine in Korea.
      Through research published in the Korean Journal of Medical History and other
      journals, the course through which medicine in Korea in the modern times has been
      formed and the content of medicine that composed that course are elucidated. This
      article concludes that the various research tend to posit the view that the
      modern history of medicine in Korea evolves through a process of accommodation
      with Western medicine rather than being a complete transplantation of Western
      medicine, and describes medicine as it is viewed by consumers rather than the
      operators of medicine. How government power or colonial power utilized medicine
      in order to stabilize their rule is also a common theme. Now, it is come time to
      interrogate the viewpoints and analytical methods of medical history studies.
      Given that medicine is one area that drives changes in Korea in contemporary
      times, the outcomes obtained through this field can be sufficiently utilized when
      studying other areas. For instance, agony over the modernity of missionary
      medicine being studied recently provides meaningful implications in understanding
      the modernity of Korea. However, the importance of substantiation should not be
      overlooked as theories not supported by thorough documentary evidence are weak.

PMID- 20671399
TI  - [The trend and prospect of studies of East Asian medical history in Korea].
AB  - Studies of East Asian medical history in Korea have progressively accumulated in
      the last twenty years. First, Korean scholars broadened the focus of research
      from China-centered research to East Asian research. Studies of Toyo medical
      history in Korea mainly concentrated on Chinese medical history. Toyo medical
      history originated from Japanese orientalism and imperialism. Today the studies
      of East Asian medical history in Korea include Korea, China and Japan, and
      attempt to deal with East Asia as a single conceptual category. Second,
      researchers in East Asian medical history are steadily increasing. They study
      Chinese medical history or Japanese medical history from universities. As they
      continue their research in academic positions, successive researchers emerge.
      Third, the number of Korean scholars remains relatively small, but they pursue
      original research. Their interests are in the discourse of East Asian medical
      history, colonial modernity, environmental history, oral history, and history of
      disease.

PMID- 20671400
TI  - [The trend and prospect of studies on the history of Western medicine in Korea.].
AB  - Studies on the history of Western medicine in Korea began to be actively
      conducted and published since the restart of the Korean Society for the History
      of Medicine in 1991, which had been originally inaugurated in 1947, and the
      publication of its official journal, the Korean Journal of Medical History in
      1992. In 1970s and 1980s, even before the start of the Journal, articles on a
      history of Western medicine were published mainly written by physicians in
      medical journals. This paper aims to provide an overview of the publications on
      the history of Western medicine in Korea, comparing papers published in the
      Journal with those published in other journals. Authors of the papers in the
      Journal are those who majored in history of medicine or history science whose
      initial educational backgrounds were medicine or science, whereas authors of the
      papers in other journals majored in Western history, economic history, social
      history, religious history, or women's history. While a large portion of papers
      in the Journal deal with medicine in ancient Greek or in modern America with no
      paper on medieval medicine, the papers in other journals deal with more various
      periods including ancient, medieval and modern periods and with diverse areas
      including France, Britain, Germany, Europe etc. Recent trends in 2000s show an
      increase in the number of researchers who published the history of Western
      medicine in other journals, total number of their publications, and the topics
      that they dealt with in their papers. In contrast, however, the number of
      researchers published in the Journal, the number of the papers and its topics -
      all decreased in recent years. Only three papers on the history of diseases have
      been published in the Journal, while eleven published in other journals. In order
      to stimulate research on the history of Western medicine in Korea, concerted
      efforts are necessary including academic communication among various disciplines,
      formulation of a long term plan to enlarge the pool of researchers and readers of
      the history of Western medicine, and development of strategic educational
      programs for both graduates and undergraduates including students of medicine and
      of humanities in Korea.

PMID- 20671401
TI  - [The methods of Western medicine in on ancient medicine].
AB  - The treatise On Ancient Medicine attests that questions of method were being
      debated both in medicine and in philosophy and is important evidence of cross
      discipline methodological controversy. The treatise On Ancient Medicine is the
      first attempt in the history of Greek thought to provide a detailed account of
      the development of a science from a starting point in observation and experience.
      The author of it criticizes philosophical physicians who attempt to systematized
      medicine by reducing it to the interaction of one or more of the opposites hot,
      cold, wet, and dry, factors. He regards the theory of his opponents as
      hypothesis(hypothesis). Medicine has long been in possession of both an arche and
      a hodos, a principle and a method, which have enabled it to make discoveries over
      a long period of time. As far as method is concerned, the traditional science of
      medicine attained the knowledge of the visible by starting from observation and
      experience, but it recommended the use of reasoning and analogies with familiar
      objects as a means of learning about the invisible. It also utilized inference
      from the visible to the visible(epilogismos) and inference from the visible to
      the invisible(analogismos). The use of analogy as a means of learning about the
      obscure was also part of the common heritage of early philosophy and medicine.
      But the author's use of the analogical method distinguishes it from Empedocles'
      well-known analogy comparisons of the eye to a lantern and the process of
      respiration to the operations of a clepsydra. According to the author,
      traditional science of medicine used functional analogy like wine example and
      cheese example to know the function of humors within the body and utilized
      structured analogy like a tube example and a cupping instrument example to
      acknowledge an organ or structure within the body. But the author didn't
      distinguish between the claim that medicine has a systematic method of making
      discoveries and very different claim that it has a systematic method of
      treatment. The reason for this is that he thought that discoveries are the end
      point of the method of investigation and the starting point of the procedures
      used in treatment.

PMID- 20671402
TI  - [Japanese travels of joseon medicine and the aspects of publication of
      collections of medical written conversations].
AB  - Of the more than two hundred collections of pildamchanghwa scattered around the
      world that are being catalogued and translated, more than forty are medical in
      nature. This paper organizes and charts the medical written conversations by
      their dates of publication and examine the various aspects of their publication.
      Medical written conversations have been collected since the Fourth Envoy. There
      are no records of medical written conversations or poetry exchange in Tsushima
      even though that was the first port of arrival for the Tongsinsa. Instead,
      sources show that written conversations and poetry exchanges mostly took place in
      Kyoto, Tokyo, and Osaka; indeed, these three cities, in that order, also have
      yielded the highest volumes of publication. The first commercially published
      collection of medical written conversations was Sanghaneuidam, published in 1713
      following the Eighth Envoy. Though Gyerimchanghwajip was published two years
      earlier in 1711, it is clear from the usage of the word changhwa in the title
      that this collection was not strictly limited to medical written conversations.
      Sanghaneuidam was an attempt by Japanese medicine to collect questions and
      answers in order to publish as medical textbooks. The Japanese medicine that was
      involved in the most written conversations was Kawamura Shunko, who was the
      editor of Sanghaneuimundap and Joseonpildam following the Tenth Envoy.
      Publications with titles containing 'eui' explicitly contemplates the targeted
      readership. Kitao Shunpo was one Japanese medicine who was less interested in
      meeting a literary scrivener, but instead sought to converse with a respected
      medicine. When the Eighth Envoy of 1711 arrived in Ogaki, Kitao followed around
      the Joseon medicines and attempted written conversations. He enlisted the aid of
      his second son Shunrin in organizing the written conversations, and published the
      collection, complete with preface, postscript, and appendices-an editorial
      decision that fully contemplated his audience. Prior to meeting Gi Du-mun, Kitao
      meticulously planned out the order of questions-that is, the table of contents
      for Sanghaneuidam. Kitao drafted his questions to serve the purpose of a medical
      textbook, edited the contents of the written conversations, and added
      illustrations before presenting the collection to the public. Seomulyuchan, one
      of the most famous leishu in Japan, contains a preface by Lee Hyeon, a scrivener
      of Joseon. Kitao, who had studied Dongeuibogam, had already possessed a vast and
      systematic knowledge of materia medica; however, he sought Lee's contributions,
      hoping that a preface written by a renowned Joseon scholar would lend his
      publication more credibility. As such, it can be inferred that the preface to
      Seomulyuchan was created as an extension of the medical written conversations.

PMID- 20671403
TI  - [The vitalism of Paul-Joseph Barthez (1734-1806)].
AB  - In The Logic of Life (1970), Francois Jacob (1920- ), Nobel Prize laureate in
      Physiology or Medicine (1965), proclaimed the end of vitalism based on the
      concept of life. More than two decades before this capital sentence condemning
      vitalism was pronounced, Georges Canguilhem (1904-1995), a French philosopher of
      medicine, already acknowledged that eighteenth-century vitalism was
      scientifically retrograde and politically reactionary or counter-revolutionary
      insofar as it was rooted in the animism of Georg Ernst Stahl (1660-1734). The
      negative preconception of the term 'vitalism' came to be established as an
      orthodox view, since Claude Bernard (1813-1878) unfairly criticized contemporary
      vitalism in order to propagate his idea of experimental medicine. An eminent
      evolutionary biologist like Ernst Mayr (1904-2005) still defended similar views
      in This is Biology (1997), arguing that if vitalists were decisive and convincing
      in their rejection of the Cartesian model (negative heuristics), however they
      were equally indecisive and unconvincing in their own explanatory endeavors
      (positive heuristics). Historically speaking, vitalists came to the forefront for
      their outstanding criticism of Cartesian mechanism and physicochemical
      reductionism, while their innovative concepts and theories were underestimated
      and received much less attention. Is it true that vitalism was merely a pseudo
      science, representing a kind of romanticism or mysticism in biomedical science?
      Did vitalists lack any positive heuristics in their biomedical research? Above
      all, what was actually the so.called 'vitalism'? This paper aims to reveal the
      positive heuristics of vitalism defined by Paul.Joseph Barthez (1734-1806) who
      was the founder of the vitalist school of Montpellier. To this end, his work and
      idea are introduced with regard to the vying doctrines in physiology and
      medicine. At the moment when he taught at the medical school of Montpellier, his
      colleagues advocated the mechanism of Rene Descartes (1596-1650), the
      iatromechanism of Herman Boerhaave (1668-1738), the iatrochemistry of Jan Baptist
      van Helmont (1579-1644), the animism of Stahl, and the organicism of Theophile de
      Bordeu (1722-1776). On the contrary, Barthez devoted himself to synthesize
      diverse doctrines and his vitalism consequently illustrated an eclectic
      character. Always taking a skeptical standpoint regarding the capacity of
      biomedical science, he defined his famous concept of 'vital principle (principe
      vital)' as the 'x (unknown variable)' of physiology. He argued that the
      hypothetical concept of vital principle referred to the 'experimental cause
      (cause experimentale)' verifiable by positive science. Thus, the vital principle
      was not presupposed as an a priori regulative principle. It was an a posteriori
      heuristic principle resulting from several experiments. The 'positivist
      hypothetism' of Barthez demonstrates not only pragmatism but also positivism in
      his scientific terminology. Furthermore, Barthez established a guideline for
      clinical practice according to his own methodological principles. It can be
      characterized as a 'humanist pragmatism' for the reason that all sort of
      treatments were permitted as far as they were beneficial to the patient.
      Theoretical incoherence or incommensurability among different treatments did not
      matter to Barthez. His practical strategy for clinical medicine consisted of
      three principles: namely, the natural, analytic, and empirical method. This
      formulation is indebted to the 'analytic method (methode analytique)' of the
      French empiricist philosopher Etienne Bonnot de Condillac (1714-1780). In
      conclusion, the eighteenth.century French vitalism conceived by Barthez pursued
      pragmatism in general, positivism in methodology, and humanism in clinics.

PMID- 20671404
TI  - [The medical assistance of Swedish Red Cross Field Hospital in Busan during and
      after the Korean war].
AB  - After the outbreak of the Korean war, the Kingdom of Sweden, a permanent neutral
      nation, dispatched the Swedish Red Cross Field Hospital(SRCFH) instead of armed
      forces for humanitarian support to the allied forces in South Korea. The Hospital
      consisted of about 170 Swedes, all volunteers. From the early part of the Korean
      War, SRCFH took part in the medical assistance in Busan. When the frontline
      advanced to northern Korea, the number of inflowing casualties to this field
      hospital decreased. At that time, earnest medical aid for civilians commenced,
      and many Koreans were treated in available beds in SRCFH. After the armistice in
      July 1953, SRCFH became the Swedish Hospital in Busan, serving not only the
      military but also civilians, and continued its humanitarian mission until April
      1957 for the Korean who were suffering from a collapsed medical system in the
      midst of war. When the Hospital returned to Sweden, it had treated over two
      million patients from twenty countries, including wounded UN allied force, Korean
      (south and north), Chinese prisoner of war and Korean civilian. Moreover, it left
      a transformative legacy, the National Medical Center in Seoul which was
      established in collaboration with other Scandinavian countries who dispatched
      medical assistance during the Korean War.

PMID- 20671405
TI  - Glomerular filtration rate and 10-year mortality in a 70-year-old community
      dwelling Japanese population.
AB  - BACKGROUND AND AIMS: The equation for Japanese estimated glomerular filtration
      rate (eGFR) was revised by measuring GFR by inulin clearance. The association of
      the new eGFR with all-cause mortality and mortality from cardiovascular disease
      (CVD) was assessed in an elderly Japanese population. METHODS: Seventy-year-old
      subjects, residents of Niigata, Japan, participated. Baseline examinations were
      carried out in June 1998. The new eGFR measure, 194 * (serum creatinine)-1.094 *
      Age-0.287 * (0.739 if female), was calculated. According to eGFR results,
      subjects were classified into normal or slightly impaired (>=60 mL/min/1.73 m2),
      moderately impaired (40-59 mL/min/1.73 m2) and severely impaired (<40 mL/min/1.73
      m2). Participants were under survey for 10 years. RESULTS: The overall survival
      rate with the Kaplan-Meier method was shorter in subjects with severely impaired
      eGFR than in those with normal, slightly or moderately impaired eGFR. Similarly,
      mortality from CVD was higher for individuals with severely impaired eGFR than
      those with normal or slightly impaired eGFR. There were no associations of
      mortality from cancer or pneumonia with eGFR. The hazard ratio by the Cox
      proportional regression model for total mortality was 3.9 times higher in the
      severely impaired group than in normal or slightly impaired groups, with
      adjustment for confounding factors. Mortality from CVD was 13.6 times higher in
      the former than in the latter, with adjustment. CONCLUSIONS: There is an
      association of the new Japanese eGFR with total mortality and CVD mortality,
      suggesting that the new equation may be independently predictive of all-cause
      mortality and mortality from CVD in the general 70- year-old Japanese population.

PMID- 20671406
TI  - Increased osteocalcin-positive endothelial progenitor cells in hypogonadal male
      patients.
AB  - OBJECTIVE: Endothelial dysfunction is considered a key factor in the development
      of cardiovascular diseases. Endothelial regeneration is necessary for the
      maintenance of endothelial function and circulating endothelial progenitor cells
      (EPC) participate of it in both direct and indirect manner. The molecular
      phenotype of EPC is not univocally defined and recent studies identified an
      osteocalcin (OCN)-positive (EPC-OCN+) subpopulation of EPC highly correlated with
      atherosclerosis progression. AIM: Considering that hypogonadism is a risk factor
      for cardiovascular diseases and atherosclerosis, we investigated the circulating
      levels of EPC-OCN+ in hypogonadal patients. SUBJECTS AND METHODS: Ten
      hypogonadotropic hypogonadal (HH) male patients and 30 healthy eugonadal men were
      evaluated for clinical status and hormonal levels. Circulating levels of
      CD34+/CD133+/kinase insert domain-receptor+ EPC and EPC-OCN+ were also determined
      by flow cytometry. RESULTS: Compared to controls, HH patients displayed lower
      FSH, LH, estradiol, testosterone, and EPC levels. On the contrary, EPC-OCN+ were
      significantly increased. CONCLUSIONS: The observed association of low levels of
      circulating EPC and increased values of EPC-OCN+ sub-population in hypogonadal
      men strengthens the significance of hypogonadism as cardiovascular risk factor.

PMID- 20671407
TI  - Alterations of pituitary adenylate cyclase-activating polypeptide-like
      immunoreactivity in the human plasma during pregnancy and after birth.
AB  - BACKGROUND: Since its discovery, several distinct effects of pituitary adenylate
      cyclase activating polypeptide (PACAP) have been established - predominantly in
      animal studies - in the nervous system, various peripheral organs as well as in
      the endocrine regulation. It is unknown whether PACAP has any effect on human
      pregnancy regarding either utero-maternal or perinatal aspects of the gestation.
      AIM: We investigated alterations of PACAP38-like immunoreactivity (PACAP38-LI) in
      the human plasma throughout normal pregnancy, during and after delivery, and its
      level in the umbilical vessels, as well as in the peripheral blood of term
      healthy newborns. MATERIALS AND METHODS: A 2 ml blood sample was used for each
      test, PACAP38-LI was determined by radioimmunoassay. RESULTS: In the 2nd and 3rd
      trimester significant elevation was observed in the PACAP38-LI compared to the
      earlier gestation and non-pregnant conditions. During delivery its level
      significantly decreased and returned to the original values 3 days after birth.
      In the neonates PACAP38-LI level of the peripheral blood was similar to that of
      healthy adults, but umbilical arteries and veins contained significantly lower
      concentrations of PACAP38-LI. Besides, the levels were lower in the umbilical
      vein compared to the artery. CONCLUSIONS: PACAP38-LI levels show sensitive change
      during normal pregnancy and delivery. Our findings suggest that the fetal organs
      actively synthesize PACAP. Further investigations are required to elucidate the
      physiological importance of the alterations observed.

PMID- 20671408
TI  - Preliminary data on effects of metformin on PED/PEA-15 cellular levels in obese
      women with polycystic ovary syndrome.
AB  - BACKGROUND: The cellular abundance of the phosphoprotein enriched in diabetes
      (PED/PEA-15), a 15 kDa protein related to insulin resistance (IR), is increased
      in women with polycystic ovary syndrome (PCOS). AIM: To investigate whether
      metformin (MET) has additive effects on PED/PEA-15 protein levels.
      MATERIAL/SUBJECTS AND METHODS: This is an open label, prospective clinical study
      over 6 months. Ten hyperandrogenic obese PCOS women [age: 24.6+/-1.6 yr; body
      mass index (BMI): 30.7+/-1.2 kg/m(2)] were treated with MET (1250 mg/day). Ten
      age- and BMI-matched normo-androgenic women were used as controls. Outcome
      measures are: PED/PEA-15 protein levels, fasting plasma glucose and insulin
      (FPI), reciprocal index of homeostasis model assessment of insulin resistance
      (1/HOMA-IR); quantitative insulin sensitivity check index (QUICKI); wholebody
      insulin sensitivity index (ISI); SHBG; total testosterone; free androgen index
      (FAI). RESULTS: At baseline FPI and PED/PEA- 15 protein levels were higher, while
      1/HOMA-IR, QUICKI, and ISI were lower (p<0.001) in MET group than in controls.
      After treatment, independently of body weight and hyperandrogenism, FPI, and
      PED/PEA-15 protein levels decreased (p=0.001 and 0.004, respectively), while,
      1/HOMA-IR, QUICKI, and ISI increased (p<0.001). PED/PEA-15 protein levels
      correlated significantly with ISI either before (r=0.636; p=0.048), and after
      treatment (r=0.758; p=0.011). CONCLUSIONS: PED/PEA-15 protein levels reduced
      after a short course of treatment with MET in a group hyperandrogenic obese PCOS
      women. This effect was independent of body weight and hyperandrogenism, and
      correlated with ISI, thus adding a further benefit to obese PCOS women.

PMID- 20671409
TI  - Male sexual disturbances in liver diseases: what do we know?
AB  - The alterations of sexual function known as the erectile dysfunction are quite
      frequent among patients affected by liver diseases and they tend to increase in
      advanced liver failure. This process is directly linked to cirrhosis or its
      treatments, such as liver transplantation, or to certain drugs (e.g. beta
      blockers). Independent of cirrhosis, other factors may cause sexual problems in
      these patients. Alcohol itself seems to worsen sexual function in the absence of
      cirrhosis. Viral hepatitis has an uncertain influence on male gonadic function
      and even antiviral therapy itself can worsen some seminal and hormonal
      parameters, although it is reversible. Quality of life may be greatly decreased
      in cases of cirrhosis where these alterations are present, so it is important to
      value and care for them, if possible. This review investigates the major male
      sexual disturbances in liver diseases of various origins.

PMID- 20671410
TI  - Subacute thyroiditis following the H1N1 vaccine.

PMID- 20671411
TI  - Diagnostic and therapeutic challenge in the management of a patient with ectopic
      adrenocorticotropin secretion.

PMID- 20671412
TI  - N-terminal pro-brain natriuretic peptide determination as a possible marker of
      cardiac dysfunction in patients with adrenal disorders.

PMID- 20671413
TI  - Endocrinology and art. Portrait of Antonietta Gonzales Lavinia Fontana de Zappis
      (1552-1614).

PMID- 20671414
TI  - Effects of anti-neoplastic treatment on sperm aneuploidy rate in patients with
      testicular tumor: a longitudinal study.
AB  - OBJECTIVE: The adjuvant radio/chemotherapy, usually employed after orchidectomy
      in patients with testicular tumors, allows a long-term survival with a consequent
      increased request for fertility. However, little is known about the effects of
      the anti-neoplastic treatment on sperm cytogenetic asset. Therefore, this
      prospective, longitudinal study was designed to evaluate the effects of radio-
      and/or chemotherapy on sperm chromosome. METHODS: Eleven patients with testicular
      tumor were enrolled and underwent sperm aneuploidy rate evaluation before and
      after 3, 6, 9, 12, 18, 24, and 36 months from radio- and/or chemo-therapy ending.
      A double and triple multicolor fluorescence in-situ hybridizations for
      chromosomes 8, 12, 18, X and Y were used to evaluate the sperm aneuploidy rate.
      To define normal sperm aneuploidy rate, 18 healthy, normozoospermic men were
      selected as controls. RESULTS: Before treatment, testicular tumor patients had a
      higher total sperm aneuploidy rate compared with normal men. Total sperm
      aneuploidy rate showed a slight, but statistically significant increase 6 months
      after anti-neoplastic treatment. This increase was mainly related to the high
      sperm aneuploidy rate found in 2 patients which remained elevated up to 12 months
      in both of them. CONCLUSION: These results showed that anti-neoplastic treatment
      caused only slight and transient sperm malsegregation events in patients with
      testicular tumor. However, since a subset of them had an elevated sperm
      aneuploidy rate for about 1 yr, we suggest to counsel them to refrain from
      fatherhood for this length of time.

PMID- 20671415
TI  - Correlation between genotype and hormonal levels in heterozygous mutation
      carriers and non-carriers of 21-hydroxylase deficiency.
AB  - Congenital adrenal hyperplasia, both in its classic (CCAH) and non-classic form
      (NCAH), is a morbid condition sustained by the absent or reduced function of one
      of the enzymes involved in cortisol biosynthesis - mainly 21 hydroxylase -
      associated with different levels of clinical androgenization. In a wide group of
      relatives of patients affected by CCAH and NCAH (no.=222) and healthy volunteers
      (no.=30), a clinical, hormonal and genetic evaluation was performed in order to
      differentiate between the condition of heterozygous mutation carrier and non
      carrier of any among 21-hydroxylase gene (CYP21) mutations. This study shows that
      clinical presentation and basal 17alpha-hydroxyprogesterone (17alpha-OHP) are not
      able to differentiate between heterozygous carriers and non-carriers, whereas
      17alpha-OHP value after ACTH bolus is significantly different between
      heterozygous carriers and non-carriers: p<0.001 with a cut-off value of 3 ng/ml
      (90% sensitivity and 74,3% specificity). Moreover, our data indicate that 17alpha
      OHP response to ACTH may be a useful tool to select subjects for genetic
      analysis.

PMID- 20671416
TI  - Resistin level is positively correlated with thrombotic complications in Southern
      Chinese metabolic syndrome patients.
AB  - BACKGROUND: The metabolic syndrome (MetS) has been found to be closely related
      with thrombotic diseases. The mechanism, however, is far from elucidated. AIM:
      This study was designed to investigate the relationship between endogenous
      resistin and thrombosis mediating factors, as well as its potential effects on
      the gene expression of cardiovascular disease biomarkers. METHODS: Ninety
      patients satisfied the MetS criteria, and 55 healthy subjects were recruited as
      part of a single-center clinical study. Plasma levels of resistin, tissue factor
      (TF), tissue factor pathway inhibitor (TFPI), tissue plasminogen activator (tPA),
      plasminogen activator inhibitor-1 (PAI-1) were measured by enzymelinked
      immunosorbent assays. The effect of resistin on the expression of cardiovascular
      disease biomarkers in human umbilical vein endothelial cells (HUVEC) was assayed
      by gene microarray. RESULTS: 1) The average levels of resistin in MetS patients
      with or without acute myocardial or cerebral infarction were significantly higher
      than those of the controls. 2) The TF and TFPI increase was higher in MetS with
      infarction patients than in MetS patients. 3) In MetS with infarction patients,
      resistin was positively correlated with TF and PAI-1 (r=0.313, p=0.008; r=0.401,
      p=0.002, respectively). 4) In HUVEC, the microarray showed that apolipoprotein C
      I, ACE, tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) and
      member 5 (CD40) genes expression were dramatically increased by resistin.
      CONCLUSION: In patients with MetS, resistin is strongly associated with
      hypercoagulative and hypofibrinolitic activities. Moreover, resistin may induce
      thrombotic complications via mediating the lipoprotein metabolism and stimulating
      inflammation.

PMID- 20671417
TI  - Effect of rosiglitazone on serum IGF-I concentrations in uncontrolled acromegalic
      patients under conventional medical therapy: results from a pilot phase 2 study.
AB  - OBJECTIVE: Current therapies for acromegaly are unsatisfactory for some patients.
      High-dose thiazolidinediones have been reported to reduce serum GH levels in
      animal models of acromegaly. The objective of the study was to evaluate the
      effect of increasing doses of rosiglitazone on serum GH and IGF-I concentrations
      in acromegalic patients. DESIGN: Phase 2 clinical trial. PATIENTS AND METHODS:
      Five consecutive patients with active and uncontrolled acromegaly under
      conventional medical therapies were treated with increasing doses of
      rosiglitazone [4 mg/day every month, starting from 8 up to 20 mg/day] added to
      previous medical therapies for acromegaly. RESULTS: Mean serum IGF-I
      concentrations decreased from 547 +/- 91 to 265 +/- 126 MUg/l (p<0,001) during
      rosiglitazone treatment: 4 patients had normal serum IGF-I concentrations, and a
      patient had lowered serum IGF-I values, although still abnormal, at the end of
      the study. On the contrary, serum GH concentrations did not significantly changed
      during rosiglitazone therapy as well as other pituitary hormones. No relevant
      side effects of rosiglitazone were observed during the study period. Quantitative
      real time PCR and Western blotting showed that rosiglitazone lowered GH-dependent
      hepatic generation of IGF-I in HepG2 cell line. CONCLUSIONS: Rosiglitazone
      reduces serum IGF-I concentrations in patients with uncontrolled acromegaly under
      conventional medical therapies, likely acting on the GH-dependent hepatic
      synthesis of IGF-I. Large studies are necessary to confirm the role of
      rosiglitazone as an adjunctive therapy for uncontrolled acromegalic patients
      under conventional medical therapies.

PMID- 20671418
TI  - Vitamin D status may contribute to serum insulin-like growth factor I
      concentrations in healthy subjects.
AB  - OBJECTIVE: The aim of the study was to evaluate whether vitamin D [25-(OH) D3]
      status affects serum IGFI concentrations in healthy subjects. DESIGN AND
      PATIENTS: Two hundred and forty-one consecutive healthy subjects were included in
      the present study. MEASUREMENTS: Serum IGF-I and 25-(OH) D3 concentrations.
      RESULTS: As expected, serum IGF-I concentrations progressively decreased with age
      (r=-0.55, p<0.0001); on the contrary, gender was not related to serum IGF-I
      levels. A positive relationship was identified between serum 25-(OH) D3 and IGF-I
      concentrations (r=0.33, p<0.0001); the 25-(OH) D3-dependent changes of serum IGF
      I concentrations were observed also when subjects were divided on the basis of
      vitamin D deficiency; in fact, those with severe 25-(OH) D3 deficiency (<20
      ng/ml) had lower (185 +/- 83 MUg/l) IGF-I values than those with mild-to absent
      25-(OH) D3 deficit (225 +/- 83 MUg/l, p=0.0004). CONCLUSIONS: 25-(OH) D3 status
      may contribute to determine serum IGF-I levels in healthy population.

PMID- 20671419
TI  - New insights for development of a safe and protective RSV vaccine.
AB  - Respiratory Syncytial Virus (RSV) is the leading cause of pneumonia and
      bronchiolitis in infants and children <1 year old, resulting in significant
      morbidity and mortality worldwide. There is currently no RSV vaccine. In the
      1960s, a formalin-inactivated RSV (FI-RSV) vaccine trial led to exacerbated
      disease upon natural infection of vaccinees, including two deaths. The causes
      involved in the disastrous results of these vaccine trials are still unclear but
      they remain the engine for searching new avenues to develop a safe vaccine that
      can provide long-term protection against this important pathogen. This article
      reviews some of the early history of RSV vaccine development,as well as more
      recent information on the interaction between RSV and the host innate and
      adaptive immune responses. A safe and efficacious vaccine for RSV will require
      "re-education" of the host immune response against RSV to prevent vaccine
      enhanced or severe RSV disease.

PMID- 20671421
TI  - Control of neural crest cell behavior and migration: Insights from live imaging.
AB  - Neural crest cells (NCCs) are a remarkable, dynamic group of cells that travel
      long distances in the embryo to reach their target sites. They are responsible
      for the formation of craniofacial bones and cartilage, neurons and glia in the
      peripheral nervous system, and pigment cells. Live imaging of NCCs as they
      traverse the embryo has been critical to increasing our knowledge of their
      biology. NCCs exhibit multiple behaviors and communicate with each other and
      their environment along each step of their journey. Imaging combined with
      molecular manipulations has led to insights into the mechanisms controlling these
      behaviors. In this review, we highlight studies that have used live imaging to
      provide novel insight into NCC migration and discuss how continued use of such
      techniques can advance our understanding of NCC biology.

PMID- 20671422
TI  - IKAP/hELP1 down-regulation in neuroblastoma cells causes enhanced cell adhesion
      mediated by contactin overexpression.
AB  - A splicing mutation in the IKBKAP gene encoding the IKAP/hELP1 (IKAP) protein was
      found to be the major cause of Familial Dysautonomia (FD). This mutation affects
      both the normal development and survival of sensory and sympathetic neurons of
      the peripheral nervous system (PNS). To understand the FD phenotype it is
      important to study the specific role played by IKAP in developing and mature PNS
      neurons. We used the neuroblastoma SHSY5Y cell line, originated from neural crest
      adrenal tumor, and simulated the FD phenotype by reducing IKAP expression with
      retroviral constructs. We observed that IKAP - down - regulated cells formed cell
      clusters compared to control cells under regular culture conditions. We examined
      the ability of these cells to differentiate into mature neurons in the presence
      of laminin, an essential extracellular matrix for developing PNS neurons. We
      found that the cells showed reduced attachment to laminin, morphological changes
      and increased cell-to-cell adhesion resulting in cell aggregates. We identified
      Contactin as the adhesion molecule responsible for this phenotype. We show that
      Contactin expression is related to IKAP expression, suggesting that IKAP
      regulates Contactin levels for appropriate cell-cell adhesion that could modulate
      neuronal growth of PNS neurons during development.

PMID- 20671423
TI  - Dissection of the one-MegaDalton JAZ1 protein complex.
AB  - Jasmonates (JAs) comprise a class of plant-specific hormones that mediate a large
      variety of processes involved in plant growth, development and defense.
      Perception of jasmonoyl-isoleucine (JA-Ile), the bioactive amino acid conjugate
      of JA, initiates the expression of JA-responsive genes through the degradation of
      the jasmonate ZIM domain (JAZ) repressor proteins and the subsequent release of
      the transcriptional activator MYC2. By using a tandem affinity purification based
      approach, we demonstrated that the Groucho/Tup1-type co-repressor TOPLESS (TPL)
      and TPL-related proteins are connected to the JAZ proteins via an adaptor
      protein, designated Novel Interactor of JAZ (NINJA). Both NINJA and TPL were
      shown to function as negative regulators of JA signaling. Here, we provide
      additional data, demonstrating that JAZ1 incorporates into high-molecular weight
      (HMW) protein complexes of > 1 MDa and speculate about their composition.

PMID- 20671424
TI  - Variable histone modifications at the A(vy) metastable epiallele.
AB  - The ability of environmental factors to shape health and disease involves
      epigenetic mechanisms that mediate gene-environment interactions. Metastable
      epiallele genes are variably expressed in genetically identical individuals due
      to epigenetic modifications established during early development. DNA methylation
      within metastable epialleles is stochastic due to probabilistic reprogramming of
      epigenetic marks during embryogenesis. Maternal nutrition and environment have
      been shown to affect metastable epiallele methylation patterns and subsequent
      adult phenotype. Little is known, however, about the role of histone
      modifications in influencing metastable epiallele expression and phenotypic
      variation. Utilizing chromatin immunoprecipitation followed by qPCR, we observe
      variable histone patterns in the 5' long terminal repeat (LTR) of the murine
      viable yellow agouti (A(vy)) metastable epiallele. This region contains 6 CpG
      sites, which are variably methylated in isogenic A(vy)/a offspring. Yellow mice,
      which are hypomethylated at the Avy LTR and exhibit constitutive ectopic
      expression of agouti (a), also display enrichment of H3 and H4 di-acetylation (p
      = 0.08 and 0.09, respectively). Pseudoagouti mice, in which A(vy)
      hypermethylation is thought to silence ectopic expression, exhibit enrichment of
      H4K20 tri-methylation (p = 0.01). No differences are observed for H3K4 tri
      methylation (p = 0.7), a modification often enriched in the promoter of active
      genes. These results show for the first time the presence of variable histone
      modifications at a metastable epiallele, indicating that DNA methylation acts in
      concert with histone modifications to affect inter-individual variation of
      metastable epiallele expression. Therefore, the potential for environmental
      factors to influence histone modifications, in addition to DNA methylation,
      should be addressed in environmental epigenomic studies.

PMID- 20671425
TI  - Gestational low protein diet in the rat mediates Igf2 gene expression in male
      offspring via altered hepatic DNA methylation.
AB  - Biological responses to environmental stress, including nutrient limitation are
      mediated in part by epigenetic modifications including DNA methylation. Insulin
      like growth factor II (Igf2) and H19 are subject to epigenetic modifications
      leading to genomic imprinting. The present study was designed to test the effect
      of maternal low protein diet on the Igf2/H19 locus in offspring. Pregnant Sprague
      Dawley rats were fed diets containing 180 g/kg casein (control) or 90 g/kg (LP)
      casein with either 1 mg/kg (LP) or 3 mg/kg folic acid (LPF). LP diet increased
      Igf2 and H19 gene expression in the liver of day 0 male offspring and the
      addition of folic acid reduced the mRNA level in LPF rats to that of the control
      group. DNA methylation in Imprinting Control Region (ICR) of Igf2/H19 locus
      increased significantly following maternal LP diet but rats fed the LPF diet did
      not exhibit the hypermethylation. The Differential Methylation Region 2 (DMR2)
      did not show any change in methylation in either LP or LPF rats. The expression
      of Dnmt1 and Dnmt3a, the members of DNA methyltransferase family, and methyl CpG
      binding domain 2 (Mbd2) was significantly increased following the maternal LP
      diet but did not differ between the control and LPF group. There is a strong
      correlation between methylation of ICR with the expression of Igf2 and H19. These
      results suggested that maternal exposure to a low protein diet and folic acid
      during gestation alters gene expression of Igf2 and H19 in the liver by
      regulating the DNA methylation of these genes. The DNA methyltransferase
      machinery may be involved into the programming of imprinted genes through the
      imprinted control region.

PMID- 20671426
TI  - Assessing monoclonal antibody product quality attribute criticality through
      clinical studies.
AB  - Recombinant therapeutic proteins, including antibodies, contain a variety of
      chemical and physical modifications. Great effort is expended during process and
      formulation development in controlling and minimizing this heterogeneity, which
      may not affect safety or efficacy, and, therefore, may not need to be controlled.
      Many of the chemical conversions also occur in vivo, and knowledge about the
      alterations can be applied to assessment of the potential impact on
      characteristics and the biological activity of therapeutic proteins. Other
      attributes may affect the drug clearance and thereby alter drug efficacy. In this
      review article, we describe attribute studies conducted using clinical samples
      and how information gleaned from them is applied to attribute criticality
      assessment. In general, how fast attributes change in vivo compared to the rate
      of mAb elimination is the key parameter used in these evaluations. An attribute
      with more rapidly changing levels may have greater potential to affect safety or
      efficacy and thereby reach the status of a Critical Quality Attribute (CQA) that
      should be controlled during production and storage, but the effect will depend on
      whether compositional changes are due to chemical conversion or differential
      clearance.

PMID- 20671427
TI  - Epigenetic differences in cytogenetically normal versus abnormal acute myeloid
      leukemia.
AB  - BACKGROUND: Methylation of tumor suppression genes (TSGs) is common in myeloid
      malignancies. However, application of this as a molecular marker for risk
      stratification in patients with AML is limited. DESIGN AND METHODS: To elucidate
      the impact of patterns of TSG methylation on outcome in cytogenetically normal
      patients, 106 samples from patients with having normal cytogenetic AML were
      evaluated for methylation of 12 genes by MSP. For sake of comparison, samples
      from patients with AML and abnormal cytogenetics (n = 63) were also evaluated.
      RESULTS: Methylation frequencies in the whole group (n = 169) were similar to
      previous reports for CDH1 (31%), ER (31%), FHIT (9%), p15 (INK4b) (44%), p73
      (25%), and SOCS1 (75%). Methylation of CTNNA1 was observed in 10%, CEBP-alpha
      in16%, CEBP-delta in 2%, MLH1 in 24%, MGMT in 11% and DAPK in 2% of AML samples.
      We find that DNA methylation was more prevalent in patients with normal compared
      to karyotypically abnormal AML for most genes; CEBPalpha (20% vs 9%), CTNNA1 (14%
      vs 4%), and ER (41% vs 19%) (p < 0.05 for all comparisons). In contrast, p73 was
      more frequently methylated in patients with karyotypic abnormalities (17% vs 38%;
      p < 0.05), perhaps due to specific silencing of the pro-apoptotic promoter
      shifting p73 gene expression to the anti-apoptotic transcript. In AML patients
      with normal cytogenetics, TSG methylation was not associated with event free or
      overall survival in a multivariate analysis. CONCLUSIONS: In patients with AML,
      TSG methylation is more frequent in patients with normal karyotype than those
      with karyotypic abnormalities but does not confer independent prognostic
      information for patients with normal cytogenetics.

PMID- 20671428
TI  - Dependency on floral resources determines the animals' responses to floral
      scents.
AB  - Animal-pollinated angiosperms either depend on cross-pollination or may also
      reproduce after self-pollination - the former are thus obligately, the latter
      facultatively dependent on the service of animal-pollinators. Analogously, flower
      visitors either solely feed on floral resources or complement their diet with
      these, and are hence dependent or not on the flowers they visit. We assume that
      obligate flower visitors evolved abilities that enable them to effectively forage
      on flowers including mechanisms to bypass or tolerate floral defences such as
      morphological barriers and repellent / deterrent secondary metabolites.
      Facultative flower visitors, in contrast, are supposed to lack these adaptations
      and are often prevented to consume floral resources by defence mechanisms. In
      cases where obligate flower visitors are mutualists and facultative ones are
      antagonists, this dichotomy provides a solution for the plants' dilemma to
      attract pollinators and simultaneously repel exploiters. In a meta-analysis, we
      recently supported this hypothesis: obligate flower visitors are attracted to
      floral scents, while facultative ones are repelled. Here, we add empirical
      evidence to these results: bumblebees and ants, obligate and facultative flower
      visitors, respectively, responded as predicted by the results of the meta
      analysis to synthetic floral scent compounds.

PMID- 20671429
TI  - The Anaphase Promoting Complex activator CCS52A, a key factor for fruit growth
      and endoreduplication in Tomato.
AB  - Tomato fruit growth is characterized by the occurrence of numerous rounds of DNA
      endoreduplication in connection to cell expansion and final fruit size
      determination. Endoreduplication occurs as an impairment of mitosis, which can
      originate from the selective degradation of M-phase-specific cyclins via the
      ubiquitin-mediated proteolytic pathway, requiring the E3 ubiquitin ligase
      Anaphase Promoting Complex/Cyclosome (APC/C). In plants CCS52A is the ortholog of
      CDH1/FZR proteins from yeast, drosophila and human, belonging to the WD40-repeat
      protein family. During fruit development, the SlCCS52A gene expression is
      specifically associated to endoreduplication in tomato. Altering SlCCS52A
      expression in either negative or positive manner impacts the extent of
      endoreduplication in fruit and affects fruit size. When SlCCS52A is down
      expressed endoreduplication is impaired during fruit growth leading to reduced
      fruit growth. However when SlCCS52A is over-expressed, endoreduplication is
      initially delayed, accounting for the altered final fruit size, but resumes and
      is even enhanced leading to fruit growth recovery, pointing at the physiological
      role of endoreduplication in growth induction during tomato fruit development.

PMID- 20671434
TI  - Malaria Vectored Vaccines Consortium (MVVC).

PMID- 20671436
TI  - Questions for European Vaccine Initiative.

PMID- 20671437
TI  - Recent advances in Ebolavirus vaccine development.
AB  - Ebolavirus is a highly infectious pathogen with a case fatality rate as high as
      90%. Currently there is a lack of licensed Ebolavirus vaccines as well as pre-
      and post-exposure treatments. Recent increases in the frequency of natural human
      Ebolavirus infections and its potential use as a bioterrorism agent makes vaccine
      development a priority for many nations. Significant progress has been made in
      understanding the pathogenesis of Ebolavirus infection and several promising
      vaccine candidates were shown to be successful in protecting NHPs against lethal
      infection. These include replication-deficient adenovirus vectors, replication
      competent VSV, HPIV-3 vectors and virus-like particle preparations. Recent
      advances in the generation of effective post-exposure immunization strategies
      highlight the possibility of developing a single dose vaccine that will confer
      full protection in humans following Ebolavirus exposure. Post-exposure protection
      is particularly important in outbreak and biodefense settings, as well as
      clinical and laboratory settings in the case of accidental exposure.

PMID- 20671438
TI  - Systems properties of proteins encoded by imprinted genes.
AB  - Genomically imprinted genes show parentally fixed mono-allelic expression and are
      important for the mammalian development. Dysregulation of genomic imprinting
      leads to several complex pathological conditions. Though the genetic and
      epigenetic regulation of imprinted genes has been well studied, their protein
      aspects are largely ignored. Here, we systematically studied a sub-network
      centered on proteins encoded by imprinted genes within human interactome. Using
      concepts of network biology, we uncover a highly connected, transitive and
      central network module of imprinted gene-products and their interacting partners
      (IGPN). The network is enriched in development, metabolism and cell cycle related
      functions and its malfunctioning ascribes error intolerance to human interactome
      network. Further, detailed analysis revealed that its higher centrality is
      determined by 'date' interactions among the proteins belonging to different
      functional classes than the 'party' interactions within the same functional
      class. Interestingly, a significant proportion of this network genetically
      associates with disease phenotypes. Moreover, the network comprises of gene-sets
      that are upregulated in leukemia, psychosis, obesity/diabetes and downregulated
      in autism. We conclude that imprinted gene-products are part of a functionally
      and topologically important module of human interactome and errors in this sub
      network are intolerant to, otherwise robust, human interactome. The findings
      might also shed light on how imprinted genes, which are rather very few,
      coordinate at protein level to pleiotropically regulate growth and metabolism
      during embryonic and post-natal development.

PMID- 20671440
TI  - HIV vaccine could use a little help.
AB  - Unexpected results of recent HIV vaccine human clinical trials are challenging
      our understanding on many facets of vaccine biology. In a Phase IIB clinical
      trial, a Merck Ad5 trivalent vaccine has surprisingly failed to provide any
      protection against the acquisition of HIV infection or suppression of post
      infection viremia levels despite having had strongest preclinical data and
      received enthusiastic support from scientists and clinicians alike. By contrast,
      ALVAC (a recombinant canarypox vector vaccine) and rgp120 vaccines that had only
      weak immunogenicity when tested alone, and faced strong disapproval for going
      into a Phase III clinical trial with their combination have demonstrated a modest
      level of protection against HIV acquisition. Although the precise correlates of
      protection against HIV are still debated, some consensus opinions start to
      emerge. In the paper, we focus on reviewing the importance of CD4+ T helper cells
      and past experience of HIV vaccine clinical trials, as well as making some
      projections on the future development in HIV vaccine research field.

PMID- 20671439
TI  - Into the world of steroids: a biochemical "keep in touch" in plants and animals.
AB  - Evolution of steroids such as sex hormones and ecdysteroids occurred
      independently in animal and plant kingdoms. Plants use phytoecdysteroids (PEs) to
      control defence interactions with some predators; furthermore, PEs can exert
      beneficial influence on many aspects of mammalian metabolism. Endocrine
      disrupting compounds such as the estrogen agonist bisphenol A (BPA) are
      widespread in the environment, posing a potential hormonal risk to animals and
      plants. Adverse BPA effects on reproductive development and function are coupled
      with other toxic effects. BPA bioremediation techniques could be developed by
      exploiting some tolerant plant species.

PMID- 20671441
TI  - ROS removal by DJ-1: Arabidopsis as a new model to understand Parkinson's
      Disease.
AB  - Reactive oxygen species represent one of the principal factors that cause cell
      death and scavenging of reactive oxygen species by superoxide dismutase-related
      pathway is essential for cell survival. The Parkinson's Disease-related DJ-1
      protein (also known as PARK7) has been implicated in resistance against oxidative
      stress in dopaminergic neurons however, its molecular mechanism has to date been
      unknown. We have used Arabidopsis thaliana as a model system to demonstrate that
      DJ-1, in both plant and mammalian cells, directly influence SOD activity in a
      highly conserved manner thereby preventing cell death. These data not only
      provides evidence for the molecular mechanisms associated with DJ-1-induced
      Parkinson's Disease but also highlight the unprecedented value of plants as a
      tool in understanding human disease mechanisms.

PMID- 20671442
TI  - Acceptability of prophylactic human papillomavirus vaccination among adult men.
AB  - OBJECTIVES: HPV vaccine acceptability was examined as part of a cohort study of
      HPV infection among adult males. RESULTS: Overall, 69% of men reported that they
      were likely or very likely to be vaccinated against HPV if a prophylactic vaccine
      were available. Men most frequently cited side effects (69%), efficacy (65%), and
      safety (63%) as the major factors that would influence their decision to be
      vaccinated against HPV. Issues of vaccine costs and efficacy were important
      considerations for men of vaccine-eligible ages (18-26 years). Men who cited cost
      as a major factor in their HPV vaccine decisions and those indicating cost as a
      potential barrier had greater intention to be vaccinated. Heterosexual men had
      less intention to be vaccinated compared to men who have sex with men. METHODS:
      Between July 2004 and June 2007, 445 adult males aged >=18 years were enrolled
      primarily from a university-based population. A structured questionnaire
      addressed HPV vaccine awareness, attitudes, and intention to be vaccinated.
      CONCLUSION: Acceptability of HPV vaccination among males is generally high. Costs
      and sexual history may influence vaccine utilization.

PMID- 20671445
TI  - Why we must improve reporting and treatment systems for needlestick injuries.

PMID- 20671446
TI  - Defining the patient-physician relationship in the era of facebook.

PMID- 20671447
TI  - More benefits of coaching.

PMID- 20671448
TI  - Commentary: models of academic-clinical partnerships: goods, better, best.
AB  - Elsewhere in this issue, Ovseiko and colleagues discuss organizational models for
      emerging academic health science centers (AHSCs) in England. In this commentary,
      the authors consider the advantages, or "goods," to organizing educational,
      clinical, and research missions within the AHSC model. Cultivating relationships
      among the three central missions of academic medicine yields good results for
      clinicians, trainees, patients, researchers, and communities, but it can also
      inspire all stakeholders to strive for better results. After outlining some of
      these benefits of current AHSC models, like those common in the United States,
      the authors discuss how close collaboration between U.S. and U.K. AHSC leaders
      could foster sharing of best practices and ultimately lead to better performance
      at AHSCs-emerging and established-in both nations. Providing excellent health
      care begins with developing the best organizational models for AHSCs, and
      identifying and pursuing such models should be a top priority.

PMID- 20671449
TI  - Commentary: improving medical education during financially challenging times.
AB  - The expectation exists that medical education will continue to improve even
      during financially challenging times. The authors reviewed their recent
      experiences in effecting positive changes and improvements in Mayo Medical School
      during a time of fiscal constraint. They successfully implemented numerous
      changes, including a major curriculum reform, while modestly reducing overall
      costs of the medical school and improving student satisfaction and learner
      outcomes. These improvements resulted from careful alignment among the
      institutional mission of serving the needs of the patient, communication with the
      faculty, involvement of the students, and streamlining of multiple processes
      throughout the school. The authors sought to eliminate excessive resource
      utilization while retaining the essence of Mayo Medical School's education
      process. The authors' experience can both encourage and inspire other schools to
      continue to improve the educational experience for their students in concert with
      meeting increasing financial pressures.

PMID- 20671450
TI  - Rock stars in academic medicine.
AB  - PURPOSE: To investigate the prevalence and characteristics of faculty rock stars,
      a subset of academic health center faculty who greatly enhance the reputation
      and/or success of their home institution, oftentimes at the expense of a
      disproportionate share of institutional resources. METHOD: In 2008, the authors
      surveyed the deans of 126 U.S. medical schools accredited by the Liaison
      Committee for Medical Education, using a 13-item instrument consisting of Likert
      scales, pick lists, and open-ended questions. RESULTS: Sixty-four (51%) surveyed
      deans responded. Respondents were more representative of public than private
      institutions (P < .001) but were proportionately representative of institutions
      of varying faculty size, U.S. New & World Report research rankings, and
      geographic location. The prevalence of rock stars was 1.42% (range 0.07%-6.42%)
      of full-time faculty. Over 74% (46/62) of deans felt that these talented faculty
      contributed to institutional prominence. Most deans were usually willing to offer
      greater resources to recruit or retain these faculty stars, and 39/62 (63%)
      believed that these individuals were a good investment. Although 53/64 (82.8%) of
      deans believed that other faculty are often or almost always aware that these
      individuals receive preferential treatment, only 37/64 (57.8%) believed that
      other faculty agree with that treatment. Fifty percent or more of deans
      (depending on the characteristic) selected self-promotion, a strong work ethic,
      opportunism, charisma, and political savvy as characteristics that were more
      common in rock stars. CONCLUSIONS: Deans appreciated both the value and the
      leadership challenges associated with the academic medical center rock star.

PMID- 20671452
TI  - Gender differences in leadership amongst first-year medical students in the small
      group setting.
AB  - PURPOSE: To investigate the extent of gender bias in the volunteerism of small
      group leaders amongst first-year medical students, and whether bias could be
      eliminated with special instructions to the students. METHOD: The gender of
      leaders in small-group sessions in a real academic setting was monitored under
      two conditions: control conditions, in which basic instructions were provided to
      participants, and intervention conditions, in which the same basic instructions
      were provided plus a brief "pep talk" on the importance of experiencing a
      leadership role in a safe environment. During the small-group sessions, an
      observer noted the gender and names of group leaders for later analysis. After a
      class debriefing, a subset of leaders and nonleaders from both the control and
      intervention groups were invited to be interviewed about their perceptions of the
      small-group experience. Interviews were tape recorded and transcribed for
      analysis. RESULTS: In 2007-2008 and 2008-2009, disproportionately fewer women
      than men volunteered to become small-group leaders under control conditions. This
      gender bias was eliminated under intervention conditions. The interviews
      illustrated how a subtle change in instructions helped some female students take
      on a leadership role. CONCLUSIONS: Gender bias in leadership in the small-group
      setting amongst medical students-even when women make up half of the class-may
      persist without targeted intervention. The authors suggest that frequent and
      consistent intervention during medical school could be an important factor in
      encouraging women to identify themselves as leaders, promoting confidence to
      consider leadership roles in medicine.

PMID- 20671453
TI  - Organizational models of emerging academic health science centers in England.
AB  - Recent government policy initiatives to foster medical innovation and high
      quality care in England have prompted academic and clinical leaders to develop
      new organizational models to support the tripartite Flexnerian mission of
      academic medicine. Medical schools and health care providers have responded by
      aligning their missions and creating integrated governance structures that
      strengthen their partnerships. In March 2009, the government officially
      designated five academic-clinical partnerships as England's first academic health
      science centers (AHSCs). As academic-clinical integration is likely to continue,
      future AHSC leaders could benefit from an analysis of models for organizing
      medical school-clinical enterprise relationships in England's emerging AHSCs. In
      addition, as the United States ponders health systems reform and universal
      coverage, U.S. medical leaders may benefit from insight into the workings of
      academic medicine in England's universal health system. In this article, the
      authors briefly characterize the organization and financing of the National
      Health Service and how it supports academic medicine. They review the policy
      behind the designation of AHSCs. Then, the authors describe contrasting
      organizational models adopted in two of the newly designated AHSCs and analyze
      these models using a framework derived from U.S. literature. The authors conclude
      by outlining the major challenges facing academic medicine in England and offer
      suggestions for future research collaborations between leaders of AHSCs in the
      United States and England.

PMID- 20671454
TI  - Changing the future of health professions: embedding interprofessional education
      within an academic health center.
AB  - Institutions are increasingly considering interprofessional education (IPE) as a
      means to improve health care and reduce medical errors in the United States.
      Effective implementation of IPE within health professions education requires a
      strategic institutional approach to ensure longevity and sustainability. In 2007,
      the Medical University of South Carolina (MUSC) established Creating
      Collaborative Care (C), an IPE initiative that takes a multifaceted approach to
      weaving interprofessional collaborative experiences throughout MUSC's culture to
      prepare students to participate in interprofessional, collaborative health care
      and research settings.In this article, the authors describe C's guiding
      conceptual foundation and student learning goals. They present its implementation
      framework to illustrate how C is embedded within the institutional culture. It is
      housed in the provost's office, and an overarching implementation committee
      functions as a central coordinating group. Faculty members develop and implement
      C activities across professions by contributing to four collaborating domains
      curricular, extracurricular, faculty development, and health care simulation-each
      of which captures an IPE component. The authors provide examples of IPE
      activities developed by each domain to illustrate the breadth of IPE at MUSC. The
      authors believe that MUSC's efforts, including the conceptual foundation and
      implementation framework, can be generalized to other institutions intent on
      developing IPE within their organizational cultures.

PMID- 20671455
TI  - Beyond "compliance": the role of institutional culture in promoting research
      integrity.
AB  - PURPOSE: To contribute data to conceptual explorations of the role of
      institutional culture in promoting research ethics and integrity. METHOD: The
      authors highlight relevant themes that emerged from a multimodal needs assessment
      conducted under the Johns Hopkins Clinical Translational Science Award regarding
      ethical issues encountered in the conduct of clinical and translational research.
      Qualitative and quantitative data were collected through a short survey targeting
      research staff, course evaluations from a research ethics and integrity education
      course attended primarily by faculty and fellows, a review of institutional
      policies on research ethics education, and in-depth interviews of key
      administrative officials. RESULTS: Major themes included the relative influence
      of regulatory compliance and relationships between research personnel at
      different levels of the organizational hierarchy on the responsible conduct of
      research. The majority of respondents (85%) expressed comfort with reporting
      suspected breaches in research integrity, but the others did not feel comfortable
      doing so for fear of professional repercussions. Respondents provided insight
      into factors in the research environment they felt were most helpful in fostering
      research integrity, particularly with respect to relationships and power
      differentials between individuals or groups. CONCLUSIONS: Compliance with
      research regulations is only one of a number of important factors in an
      institution's ethical culture of research. Equally important are a clear
      articulation of the ethical reasoning that underlies the regulations, and efforts
      to redress power imbalances by encouraging open communication. Other ways of
      improving relationships among various members of the academic research team
      should be the focus of future investigations.

PMID- 20671456
TI  - Learning about teams by participating in teams.
AB  - PURPOSE: As the work of academic health centers becomes increasingly oriented
      toward teams and collaboration, professional development in effective team skills
      becomes increasingly important. The authors sought to determine whether a
      transdisciplinary program for enhancing teamwork was effective in educating
      individual team members to translate lessons into productive outcomes of their
      own institutions' teams. METHOD: Between 2006 and 2008, the authors used the
      Learning in Teams model of collaborative team development to design and implement
      two applications of a national professional development program for members of
      academic organizations' teams. The purpose of the program was to foster
      individual skill development in collaborative teamwork. Using pre/post surveys to
      determine changes in team functioning over the course of the program, the authors
      evaluated participants' perceptions of the effectiveness of their professional
      development programs' learning teams and of their home institutions' teams. They
      analyzed narrative reports of participants' institutional teams' progress for
      elements including team task management, member dynamics, and institutional
      outcomes. RESULTS: Pre/post self-assessments of team performance and
      participants' progress reports on their home teams revealed enhancement of team
      skills, including clarifying team charge, exploring team purpose, and evaluating
      team process. Program participants improved their team skills and enhanced
      productivity of their institutions' teams. CONCLUSIONS: The Learning in Teams
      model can support individual team skills development, enhance institutional team
      performance in academic health centers, and provide a basis for research in team
      skills development and team process improvement. It can be adapted to various
      programs to enhance skills in teamwork.

PMID- 20671457
TI  - Cost-effectiveness of a hospitalist service in a public teaching hospital.
AB  - PURPOSE: The authors report implementing an academic hospitalist team as a cost
      effective solution to the problem of an inpatient census that exceeds their
      public hospital's teaching service limits. Medi-Cal (California's Medicaid
      program) per diem reimbursement was the primary source of revenue, which rendered
      moot some traditional advantages of hospitalist services. METHOD: The authors
      assessed cost-effectiveness by comparing average inpatient census, payment denial
      rate, and Medi-Cal reimbursement for internal medicine in 2008 and in 2007. They
      also focused on Medi-Cal patients admitted with low-risk chest pain in 2008,
      comparing the length-of-stay and denied-day rate data with data from 2005.
      RESULTS: Overall Medi-Cal reimbursement was $2,310,000 higher in 2008 than in
      2007. Overall payment denial rate fell from 29% to 27.4%, while yearly admissions
      increased from 8,069 to 8,643, and the average daily census increased from 97.7
      to 107.1 patients. For low-risk chest pain admissions, length of stay decreased
      from 2.48 to 1.92 days, denial rate decreased from 43.8% to 31.8%, and average
      reimbursement per inpatient day increased from $787 to $955. Total salary outlay
      for the first year of the service was approximately $310,000. CONCLUSIONS: By
      reducing payment denials and increasing the inpatient census, hospitalists were
      able to more than offset their compensation with a substantial increase in
      revenue under per diem reimbursement, which adds a new dimension to prior reports
      of cost-effectiveness of hospitalist services in diagnosis-based, capitated, or
      fee-for-service reimbursement systems. Hospitalists are a cost-effective solution
      to the problem of increasing inpatient workloads at public teaching hospitals.

PMID- 20671458
TI  - The cost of pursuing a medical career in the military: a tale of five
      specialties.
AB  - PURPOSE: The physician payment system is a focus of potential reform in the
      United States. The authors explored the effects of the military's method of
      physician payment on physicians' returns on educational investment for several
      specialties. METHOD: This retrospective, observational study used national data
      from 2003 and standard financial techniques to calculate the net present value
      the current value of an expected stream of cash flows at a particular rate of
      interest-of the educational investments of medical students in ten 30-year career
      paths: either military or civilian careers in internal medicine, psychiatry,
      gastroenterology, general surgery, or orthopedics. RESULTS: At a 5% discount
      rate, in the civilian world, the lowest return on an educational investment
      accrued to psychiatrists ($1.136 million) and the highest to orthopedists ($2.489
      million), a range of $1.354 million. In the military, the lowest returns accrued
      to internists ($1.377 million) and the highest to orthopedists ($1.604 million);
      however, the range was only $0.227 million, one-sixth that found in the civilian
      sector. The authors also found that most military physicians do not remain in the
      military for their full careers. CONCLUSIONS: Choosing a military career
      substantially decreases the net present value of an educational investment for
      interventionalists, but it does so only modestly for primary care physicians.
      Further, a military career path markedly diminishes specialty-specific variation
      in the net present values of educational investment. Adopting a military
      structure for engaging medical students might help reverse the current trend of
      declining interest in primary care.

PMID- 20671459
TI  - Medical student sexuality: how sexual experience and sexuality training impact
      U.S. and Canadian medical students' comfort in dealing with patients' sexuality
      in clinical practice.
AB  - PURPOSE: To determine factors associated with students' comfort in addressing
      patients' sexuality in the clinical context. METHOD: The authors invited students
      enrolled in MD-degree-granting and osteopathic medical schools in the United
      States and Canada to participate in an anonymous Internet survey between February
      and July 2008. The survey assessed ethnodemographic factors and sexual history.
      Respondents also completed the Center for Epidemiologic Studies Depression Scale.
      Male respondents completed the International Index of Erectile Function and the
      Premature Ejaculation Diagnostic Tool. Female respondents completed the Female
      Sexual Function Index and the Index of Sex Life. The authors used descriptive
      statistics, ANOVA, and multivariable logistic regression to analyze responses.
      RESULTS: The authors' analyses included 2,261 completed survey responses: 910
      from men, 1,343 from women, and 8 from individuals who self-identified as "other"
      gendered. Over 53% of respondents (n = 1,206) stated that they felt they had not
      received sufficient training in medical school to address sexual concerns
      clinically. Despite this, 81% of students (n = 1,827) reported feeling
      comfortable dealing with their patients' sexuality issues. Students with limited
      sexual experience, students at risk for sexual problems, and students who felt
      that they had not been trained adequately were less likely to report being
      comfortable talking to patients about sexual health issues. CONCLUSIONS:
      Perception of inadequate sexuality training in medical school and personal issues
      pertaining to sex may be associated with students' difficulty in addressing
      patients' sexuality. Adequate training is preeminently associated with feeling
      comfortable addressing patients' sexuality and should be a priority for medical
      education.

PMID- 20671460
TI  - Formative experiences of emerging physicians: gauging the impact of events that
      occur during medical school.
AB  - PURPOSE: Emotional development, an important component of nascent professional
      competence, is likely to be shaped by specific formative experiences. This study
      sought to identify and gauge the impact of highly evocative experiences occurring
      during medical school. METHOD: A 34-item list of candidate formative experiences
      was developed through focus group meetings of "colleges program"-affiliated
      student-advising faculty. The resulting survey instrument was administered to 216
      graduating medical students at the Johns Hopkins University School of Medicine in
      2007 and 2008 in a cohort study. Primary outcomes were exposure rates for the
      experiences and students' ratings of impact for those that occurred. RESULTS: One
      hundred eighty-one students (84%) responded. All events were experienced by >25%
      of students. Two events were described by most as having tremendous impact:
      "finding an exceptional role model" and "identifying a perfect area of medicine."
      Other prevalent events with strong impact included "a special patient-care
      experience," "working well with a team," "seeing a patient whose life was saved,"
      "encountering a negative role model," "seeing a patient die," "seeing a patient
      experience severe pain," and "a bad clinical experience." Factor analysis
      revealed three event clusters: "inspiring experiences," "mortality-related
      experiences," and "negative experiences relating to the learning environment."
      CONCLUSIONS: Specific formative experiences have especially strong impacts on
      medical students. Whereas the intrinsic value of such experiences should continue
      to drive educational design, increased awareness of the diversity and range of
      formative experiences will prepare educators to more effectively guide positive
      emotional development, enhancing personal and professional growth during medical
      school.

PMID- 20671461
TI  - Medicine and the arts. "A Woman drest by Age" by Margaret Lucas Cavendish.
      Commentary.

PMID- 20671463
TI  - Longitudinal research databases in medical education: facilitating the study of
      educational outcomes over time and across institutions.
AB  - Many education research questions cannot be answered using participants from one
      institution or short periods of follow-up. In response to societal demands for
      accountability and evidence of effectiveness, new models of research must be
      developed to study the outcomes of educational activities. Following the 2007
      Millennium Conference on Medical Education Research, organizers assigned a task
      force to explore the use of longitudinal databases in education research. This
      article summarizes the task force's findings. Similar to the Framingham studies
      in clinical medicine, longitudinal databases assemble prospectively collected
      information to retrospectively answer questions of interest. Many studies using
      such databases have been published. The task force identified three general
      approaches to database-type research. First, institutions can obtain identified
      information from existing sources, link it with school-specific information and
      other identified information, deidentify it, and merge it with similar
      information from other collaborating schools. Second, researchers can obtain from
      existing sources deidentified information on large samples and explore
      associations within this dataset. Third, investigators can design and implement
      databases to prospectively collect trainee information over time and across
      multiple institutions for the purpose of education research. Although costly,
      such comprehensive, purpose-built databases would ensure the availability of
      information needed to answer a variety of medical education research questions.
      Millennium Conference participants believed that stakeholders should explore the
      funding and development of such prospective databases. In the meantime, education
      researchers should use existing sources of individualized learner data to better
      understand how to develop competent, compassionate clinicians.

PMID- 20671464
TI  - Challenging traditional premedical requirements as predictors of success in
      medical school: the Mount Sinai School of Medicine Humanities and Medicine
      Program.
AB  - PURPOSE: Students compete aggressively as they prepare for the MCAT and fulfill
      traditional premedical requirements that have uncertain educational value for
      medical and scientific careers and limit the scope of their liberal arts and
      biomedical education. This study assessed the medical school performance of
      humanities and social science majors who omitted organic chemistry, physics, and
      calculus, and did not take the MCAT. METHOD: The authors compared and contrasted
      the academic outcomes of 85 Humanities and Medicine Program (HuMed) students at
      Mount Sinai School of Medicine with those of their 606 traditionally prepared
      classmates for the 2004-2009 graduating classes. The authors analyzed basic
      science knowledge, clerkship performance, humanism, leadership, community
      service, research fellowships, distinctions, and honors. RESULTS: There were no
      statistically significant differences between the groups in clerkship honors
      other than psychiatry (HuMed students outperformed their peers, P < .0001) or in
      commencement distinctions or honors. Although HuMed students were significantly
      more likely to secure a scholarly-year mentored project (P = .001), there was no
      difference in graduating with distinction in research (P = .281). HuMed students
      were more likely to have lower United States Medical Licensing Examination Step 1
      scores (221 +/- 20 versus 227 +/- 19, P = .0039) and to take a nonscholarly leave
      of absence (P = .0001). There was a trend among HuMed students toward residencies
      in primary care and psychiatry and away from surgical subspecialties and
      anesthesiology. CONCLUSIONS: Students without the traditional premedical
      preparation performed at a level equivalent to their premedical classmates.

PMID- 20671465
TI  - Monkey see, monkey don't.

PMID- 20671466
TI  - AM last page: paths to national service as a military physician.

PMID- 20671467
TI  - It's all 'nursing' work.

PMID- 20671468
TI  - Who's the 'real' nurse?

PMID- 20671470
TI  - A better injection site.

PMID- 20671471
TI  - Home mechanical ventilation.

PMID- 20671485
TI  - Fast tracking advanced practice.

PMID- 20671488
TI  - March madness.

PMID- 20671493
TI  - Original research: parents and children with cystic fibrosis.
AB  - OBJECTIVE: A survey was conducted to estimate how many adult patients with cystic
      fibrosis who receive care at centers accredited by the Cystic Fibrosis Foundation
      (CFF) also have biological children with the disease. METHODS: A six-item
      questionnaire was sent to 144 CFF-accredited care centers and satellites. After
      one month, a reminder e-mail was sent to the nonresponding centers. RESULTS: A
      total of 119 responses were received. Forty (34%) of the responding centers
      reported having at least one and as many as five patients with cystic fibrosis
      who also had biological children with the disease. A total of 66 such patients
      were identified. Of these, 39 (59%) were newly diagnosed themselves as a
      consequence of prenatal testing or a child's diagnosis. CONCLUSION: Despite some
      study limitations, these findings show that a number of people with cystic
      fibrosis are having children who also have the disease. Moreover, many parents
      are learning that they have cystic fibrosis only after their child is diagnosed.
      Further research is needed to better estimate both the proportion of adults with
      cystic fibrosis who are having children with the disease and the proportion late
      diagnosed, as well as to explore the psychosocial needs of these patients and
      their children. KEYWORDS: cystic fibrosis, cystic fibrosis research, family
      planning, genetic testing, carrier testing, newborn screening.

PMID- 20671495
TI  - Cultivating quality: reducing rates of catheter-associated urinary tract
      infection.

PMID- 20671496
TI  - Environments and health: leftover drugs in the water supply: don't flush those
      pills!

PMID- 20671497
TI  - Sexually speaking: sexual changes during and after pregnancy.

PMID- 20671499
TI  - Material safety data sheets in health care.

PMID- 20671501
TI  - Sepsis and pneumonia take their toll.

PMID- 20671502
TI  - Mary Maud Brewster.

PMID- 20671509
TI  - 'Hi, Who's on the Line?'.

PMID- 20671510
TI  - Miss orienting nurse.

PMID- 20671511
TI  - Liposomal cisplatin: a new cisplatin formulation.
AB  - Over the last three decades, cisplatin has been one of the most effective
      cytotoxic agents, but its administration has been hindered by its nephrotoxicity,
      neurotoxicity and myelo toxicity. Recently, liposomal cisplatin, lipoplatin, has
      been formulated and tested thoroughly in preclinical (in vitro) and phase I, II
      and III trials, as documented in the literature. Experiments in animals showed
      that lipoplatin is less toxic than cisplatin and that it produces tumour
      reduction. The histological examination of treated tumours from mouse xenografts
      was consistent with apoptosis in the tumour cells in a mechanism similar to that
      of cisplatin. Lipoplatin infusion in patients and measurements of platinum levels
      in tumour specimens showed 10-50 times higher levels in tumours and metastases
      than in the adjacent normal specimens. A phase I-II study using a combination of
      lipoplatin and gemcitabine in pretreated patients (with disease progression or
      stable disease) with advanced pancreatic cancer was conducted. No nephrotoxicity
      was observed. With lipoplatin monotherapy the dose-limiting toxicity was
      determined to be 350 mg/m and the maximum tolerated dose 300 mg/m; when used in
      combination with paclitaxel the dose-limiting toxicity for lipoplatin was 250
      mg/m and for paclitaxel 175 mg/m, and the maximum tolerated dose was 200 and 175
      mg/m, respectively. In two phase II randomized studies comparing the lipoplatin
      combination versus the cisplatin combination, it was found that the former was
      statistically significantly less toxic than the latter, whereas the response rate
      and survival were similar. Up to now, the data on lipoplatin treatment in
      malignant tumours are quite impressive, because of the negligible toxicity and
      because it is equal if not superior to cisplatin with regard to response rate.
      This review aims to chronologically document publications relevant to liposomal
      cisplatin to date.

PMID- 20671512
TI  - Successful dexrazoxane treatment of a potentially severe extravasation of
      concentrated doxorubicin.
AB  - Dexrazoxane is now authorized for the treatment of anthracycline extravasations.
      Several clinical cases of doxorubicin extravasation treated with dexrazoxane have
      been reported to date, but detailed cases have not been published. We report a
      case of a successful dexrazoxane treatment for a potentially severe extravasation
      of concentrated doxorubicin. We also describe objective outcome of this
      treatment, drug tolerance to dexrazoxane and long follow-up. A 29-year-old man
      diagnosed with Hodgkin's lymphoma was prescribed a regimen including 90 mg of
      doxorubicin in a 50 ml infusion using a reduced occlusion infusion pump. After
      this infusion, the patient complained of pain around the site of injection and
      presented a 10x6-cm swollen area with erythema and inflammation. A significant
      portion of doxorubicin was extravasated. Dexrazoxane was prescribed as an
      antidote. Side effects of dexrazoxane were restricted to reversible hematological
      toxicity, nausea, and vomiting. The next day, the inflammation of the
      extravasation area was reduced. On day 7, a painless mild induration in the
      extravasated area was the only remaining sign of the extravasation. On day 40, an
      arm nuclear magnetic resonance image showed no focal injuries. At 6-month follow
      up, the patient has no sequelae. The two risk factors that could have increased
      the severity of the extravasation are the use of an infusion pump and the high
      drug concentration. Dexrazoxane proved to be effective and moderately well
      tolerated. A dexrazoxane stock in oncological facilities could help to promptly
      handle emergencies like this. Anthracyclines can be administered using reduced
      occlusion infusion pumps, but it seems preferable to always administer a free
      running infusion to minimize accidents like this one.

PMID- 20671514
TI  - Pulmonary embolism in patients over 90 years of age.
AB  - PURPOSE OF REVIEW: There is some uncertainty about the management of pulmonary
      embolism in nonagenarians. RECENT FINDINGS: Immobility plays an important role in
      the pathogenesis of venous thromboembolism in the elderly. Of 858 nonagenarians
      with acute venous thromboembolism enrolled in Registro Informatizado de la
      Enfermedad TromboEmbolica venosa registry, 41% had recent immobility and only
      7.7% had recent surgery. Comorbidity is common: 19% of patients had chronic heart
      failure, 9.8% chronic lung disease, 14% cancer, and 63% had abnormal creatinine
      levels. Most (92%) of the patients were initially treated with low-molecular
      weight heparin and then 46% switched to antivitamin K drugs. During follow-up,
      the proportion of patients who developed recurrent venous thromboembolism (4.9%)
      or major bleeding complications (6.2%) was similar, but the 5.9% of fatal
      pulmonary embolisms by far exceeded the 2.2% of fatal bleeding events. The most
      common clinical symptoms are isolated dyspnea and syncope, and presentation as
      pulmonary infarction (with hemoptysis and pleuritic chest pain) is rare. SUMMARY:
      In patients aged at least 90 years presenting with acute pulmonary embolism, the
      incidence of fatal pulmonary embolism by far outweighs the incidence of fatal
      bleeding, and pulmonary embolism is the most common cause of death. Thus, there
      seems to be more reason to be concerned about fatal pulmonary embolism than about
      bleeding in elderly patients presenting with pulmonary embolism.

PMID- 20671515
TI  - Disorders of pulmonary circulation.

PMID- 20671516
TI  - A pragmatic approach to diagnosing and treating neurosarcoidosis in the 21st
      century.
AB  - PURPOSE OF REVIEW: Neurosarcoidosis may be a serious complication of sarcoidosis.
      As the presentation of neurosarcoidosis is manifold, solitary nervous system
      sarcoidosis without systemic activity remains a difficult diagnosis. Appropriate
      treatment may be a dilemma. RECENT FINDINGS: Most neurosarcoidosis patients
      present with neurological symptoms as the first manifestation. Whole-body
      fluorodeoxyglucose positron emission tomography has been found useful in
      neurological patients suspected of sarcoidosis. Small-fiber neuropathy is
      commonly associated with sarcoidosis and can cause significant morbidity to
      afflicted patients. New drugs such as antitumor necrosis factor alpha have been
      proven valuable in the treatment of neurosarcoidosis in different locations.
      Progressive multifocal leucencephalopathy should be considered in neurosarcoid
      patients, especially when treatment fails. SUMMARY: In this paper an update on
      clinical manifestations of neurosarcoidosis, diagnostic dilemmas, and therapeutic
      options is provided.

PMID- 20671517
TI  - Vitamin D and sarcoidosis.

PMID- 20671518
TI  - Bibliography. Disorders of the pulmonary circulation. Current world literature.

PMID- 20671520
TI  - Pathogenesis of Sjogren's syndrome and therapeutic consequences.
AB  - PURPOSE OF REVIEW: To summarize recent findings on new pathogenic mechanisms of
      interaction between genetic and environmental factors and between innate and
      adaptive immunity in primary Sjogren's syndrome and to reconcile pathogenesis and
      treatment by focusing on the crucial pathogenic steps that could be targeted by
      emerging therapies. RECENT FINDINGS: Regarding genetic predisposition, the
      functional relevance of IRF5 and STAT4 gene polymorphisms in the activation of
      type I interferon pathways has been demonstrated. It has also been shown that the
      isolated stimulation of innate immunity in mice can result in dryness, which
      precedes lymphocytic infiltrates in salivary glands. In animal models, possible
      environmental triggers of the disease, such as oestrogen deficiency and/or
      infection by Epstein-Barr virus, can lead to innate immune followed by autoimmune
      epithelitis. The IFN-BAFF-B lymphocyte pathogenic axis is, therefore, targeted by
      numerous drugs currently in evaluation. The development of consensus disease
      activity scores and patient-related outcomes might help to initiate new
      controlled trials. The first positive randomized controlled trial with rituximab
      has been recently published. SUMMARY: Hopefully, persistent and joint efforts by
      many teams to improve the knowledge on the pathogenesis of the disease may allow
      identification of new therapeutic targets in Sjogren's syndrome.

PMID- 20671521
TI  - Osteoarthritis: new perspectives.

PMID- 20671523
TI  - Central nervous system vasculitis in children.
AB  - PURPOSE OF REVIEW: To review the current literature of childhood primary and
      secondary central nervous system (CNS) vasculitis and to evaluate the growing
      differential diagnosis of inflammatory and noninflammatory brain diseases. RECENT
      FINDINGS: Primary angiitis of the central nervous system in children (cPACNS) is
      a reversible cause of severe neurological deficits and/or psychiatric symptoms.
      This disease is classified into subtypes based on distinct clinical and
      radiological features, treatment strategies, and disease trajectories. Also, the
      increased diagnostic yield from elective brain biopsies in children has improved
      our ability to diagnose angiography-negative cPACNS. Over the past few years, the
      differential diagnosis for cPACNS has rapidly expanded due to the
      characterization of novel inflammatory and noninflammatory brain diseases.
      Specifically, vasoconstrictive disorders and neuronal antibody-associated
      conditions have now been described in children and have overlapping clinical
      features with cPACNS. SUMMARY: This review summarizes the recent data on
      diagnosis, treatment, and prognosis of cPACNS. It also addresses the evolving
      differential diagnosis for CNS vasculitis. Our improved understanding of these
      disorders allows a tailored diagnostic approach leading to rapid diagnosis and
      initiation of therapy in these potentially reversible conditions.

PMID- 20671524
TI  - Current world literature.

PMID- 20671522
TI  - Monogenic autoinflammatory diseases: new insights into clinical aspects and
      pathogenesis.
AB  - PURPOSE OF REVIEW: The genetic and clinical characterizations of monogenic
      autoinflammatory syndromes have led to ground breaking insights into the
      regulation of inflammatory responses to endogenous and exogenous inducers or
      triggers of inflammation and continue to uncover key inflammatory pathways of the
      innate immune system. This article summarizes recent progress in the clinical
      aspects and understanding of the pathogenesis of this growing spectrum of
      diseases. RECENT FINDINGS: The understanding of the spectrum of organ
      manifestations in autoinflammation was expanded by the discovery of two novel
      monogenic diseases both caused by the absence of an anti-inflammatory signal and
      added evidence that increased IL-1 signaling can cause aseptic osteolytic bone
      lesions and that the absence of IL-10 signaling causes inflammatory enterocolitis
      in neonates. New knock in animal models for TNF-receptor-associated periodic
      syndrome, and familial Mediterranean fever and cryopyrin-associated periodic
      syndromes allow insights into the complexity of the dysregulated immune pathways.
      Exploring 'triggers' of the NLRP3 inflammasome spurred studies of tissue
      inflammation in diseases including gout and those that previously have not been
      considered inflammatory in nature such as diabetes, fibrosing lung disease and
      possibly coronary artery disease. SUMMARY: The genetic characterization of a
      growing number of monogenic autoinflammatory diseases has provided important
      insights into the phenotypic expression of single gene disorders and the
      complexity of the dysregulated inflammatory pathways leading to clinical disease.
      Knowledge obtained from these disorders is pertinent to a number of common
      disorders and provides new targets for drug development.

PMID- 20671525
TI  - (Zebra) fishing for relevant genes in heart regeneration.

PMID- 20671526
TI  - Aortic root surgery in Marfan syndrome: Bentall procedure with the composite
      mechanical valved conduit versus David reimplantation with the Valsalva graft.

PMID- 20671527
TI  - Numbers don't tell the whole story.

PMID- 20671528
TI  - Improve RN retention through transformational leadership styles.

PMID- 20671529
TI  - Outcome measurement matters.

PMID- 20671530
TI  - Quality is NOT an irreconcilable difference!

PMID- 20671531
TI  - Social media for nurse managers: what does it all mean?

PMID- 20671532
TI  - The COMPENSATION TUMBLE.

PMID- 20671533
TI  - Unraveling Guillain-Barre syndrome.

PMID- 20671535
TI  - Is your patient satisfaction in the bag?

PMID- 20671536
TI  - Becoming the CNE: the first 100 days.

PMID- 20671537
TI  - Establishing healthy union relationships and the "best" unit in the hospital.

PMID- 20671538
TI  - The essential value of projects in faculty development.
AB  - Projects--planned activities with specific goals and outcomes--have been used in
      faculty development programs to enhance participant learning and development.
      Projects have been employed most extensively in programs designed to develop
      faculty as educators. The authors review the literature and report the results of
      their 2008 study of the impact of projects within the Pennsylvania State
      University College of Medicine Junior Faculty Development Program, a
      comprehensive faculty development program. Using a mixed-methods approach, the
      products of project work, the academic productivity of program graduates, and the
      impact of projects on career development were analyzed. Faculty who achieved the
      most progress on their projects reported the highest number of academic products
      related to their project and the highest number of overall academic achievements.
      Faculty perceived that their project had three major effects on their
      professional development: production of a tangible outcome, development of a
      career focus, and development of relationships with mentors and peers. On the
      basis of these findings and a review of the literature, the authors conclude that
      projects are an essential element of a faculty development program. Projects
      provide a foundation for future academic success by enabling junior faculty to
      develop and hone knowledge and skills, identify a career focus and gain
      recognition within their community, generate scholarship, allocate time to
      academic work, and establish supportive relationships and collaborative networks.
      A list of best practices to successfully incorporate projects within faculty
      development programs is provided.

PMID- 20671539
TI  - The Emphasis Program: a scholarly concentrations program at Vanderbilt University
      School of Medicine.
AB  - In 1999, a faculty committee at Vanderbilt University School of Medicine reviewed
      the mission and goals of the school and determined that graduates should receive
      initial preparation to develop scholarly careers in medicine. The authors
      describe the design of a scholarly projects course, the Emphasis Program, which
      is required of all students in the first two years of medical school. Each
      student undertakes a mentored project in one of nine areas of scholarship related
      to medicine. Curricular time is devoted to the program during the first two
      academic years, and students also spend eight weeks working on their projects in
      the intervening summer. The program includes a core didactic curriculum on topics
      common to all areas of scholarly work, such as biostatistics and study design.
      Implemented with the entering class of 2004, 467 students had completed the
      program as of May 2010, and only two students have been unable to complete
      projects in the allotted time. The majority of graduating seniors reported that
      they felt this was a valuable aspect of their medical education. Whereas the
      program offers a broad spectrum of scholarship opportunities, most students have
      selected projects in more traditional areas, such as laboratory-based research
      and patient-oriented research. The authors describe early successes in meeting
      program goals as well as some of the ongoing challenges of administering a
      required but individualized program of this nature.

PMID- 20671540
TI  - Physician numeracy as the basis for an evidence-based medicine curriculum.
AB  - Most medical schools and postgraduate programs devote some time to teaching
      evidence-based medicine (EBM). EBM encompasses five essential skills, including
      constructing a sound clinical question, literature searching, critical appraisal,
      gaining a full understanding of study results, and integration of results into
      patient care. Gaining a full understanding of results requires understanding the
      statistical aspects of and terminology associated with the design, analysis, and
      results of original research--hereby referred to as physician numeracy.
      Physicians and physicians-in-training recognize the importance of these concepts
      but are uncomfortable with and demonstrate poor knowledge of the quantitative
      aspects of research. This is not surprising since few curricula include physician
      numeracy. Current approaches to teaching EBM rely on journal clubs, which have
      not been shown to improve participants' self-perceived EBM skills. In this paper
      we describe a novel approach to teaching EBM which makes use of five guiding
      principles: (1) Journal clubs have important limitations, (2) understanding the
      quantitative aspects of research promotes an in-depth understanding of papers,
      (3) physician numeracy can form the basis of an EBM course, (4) consumers of
      original research ought to determine what is useful about a paper rather than
      whether or not it is useful, and (5) numeracy should encompass only those
      concepts needed to accurately interpret evidence and apply it to individual
      patients. An EBM curriculum based on physician numeracy is described, together
      with the challenges inherent to this approach.

PMID- 20671541
TI  - Detrimental clinical interaction between ritonavir-boosted protease inhibitors
      and vinblastine in HIV-infected patients with Hodgkin's lymphoma.
AB  - In order to analyze the clinical relevance of the pharmacokinetic interactions
      between vinblastine and antiretrovirals described in literature, we evaluated all
      HIV-infected patients with Hodgkin's lymphoma treated with vinblastine-containing
      regimens and combination antiretroviral therapy, in a single clinical center. The
      use of protease inhibitors was independently associated with WHO grade III-IV
      neutropenia. Moreover, an inverse correlation between dosage of ritonavir and
      mean nadir neutrophil count was found. The concomitant administration of
      vinblastine-containing chemotherapy regimens with protease inhibitors can lead to
      higher levels of neutropenia than those of different classes of drugs such as
      nonnucleoside reverse transcriptase inhibitors or integrase inhibitors.

PMID- 20671542
TI  - HIV-1 Gag evolution in recently infected human leukocyte antigen-B*57 patients
      with low-level viremia.
AB  - We studied viral evolution in five human leukocyte antigen (HLA)-B*57 patients
      recently infected with HIV-1. Escape mutations in HLA-B*57-restricted Gag
      epitopes were present at study entry in all patients, but were not associated
      with significant increases in viremia. Conversely, no new escape mutations in HLA
      B*57-restricted epitopes or known compensatory mutations were detected in
      patients who experienced significant increases in viremia. Thus, the development
      of escape mutations alone does not determine virologic outcome in recently
      infected HLA-B*57 patients.

PMID- 20671543
TI  - Prevention of invasive pneumococcal disease among HIV-infected adults in the era
      of childhood pneumococcal immunization.
AB  - OBJECTIVE: Human immunodeficiency virus (HIV) infection and AIDS increase the
      risk of invasive pneumococcal disease (IPD). We evaluated IPD among HIV-infected
      adults over a 10-year period in the US to identify opportunities for prevention
      of IPD among HIV-infected adults. DESIGN: IPD and HIV surveillance in seven
      population-based and laboratory-based Active Bacterial Core surveillance areas.
      METHODS: IPD cases were adults 18-64 years old with pneumococcus isolated from a
      normally sterile site during 1998-2007. Isolates were serotyped using the
      Quellung reaction. HIV/AIDS status was determined by medical record review. We
      calculated incidence of IPD among adults with AIDS using national case-based
      surveillance data. RESULTS: Of 13 812 IPD cases among 18-64-year-olds, 3236 (23%)
      occurred among HIV-infected adults (with or without AIDS) and 1313 (10%) occurred
      among the subset of HIV-infected adults with AIDS. Compared with the period (1998
      1999) before childhood 7-valent pneumococcal conjugate vaccine (PCV7)
      introduction in the US, the overall incidence of IPD among adults with AIDS
      decreased 25% from 399 to 298 cases per 100 000 by 2007 (P = 0.008). In 2006
      2007, 8, 39 and 55% of IPD cases among adults with AIDS were caused by serotypes
      included in the 7-valent PCV, 13-valent PCV and 23-valent pneumococcal
      polysaccharide vaccines, respectively. CONCLUSION: Sustained declines in IPD have
      occurred among adults with AIDS in the US, but incidence remained high 7 years
      after PCV7 introduction. More aggressive efforts, including HIV-prevention
      measures and the use of new PCVs in children and possibly HIV-infected adults,
      are necessary to further reduce IPD among HIV-infected adults.

PMID- 20671545
TI  - Can migrants from high-endemic countries cause new HIV outbreaks among
      heterosexuals in low-endemic countries?
AB  - OBJECTIVES: To investigate how the sexual behaviour of migrants originating from
      HIV-endemic countries affects the spread of HIV among heterosexuals in low
      endemic countries. METHODS: A mathematical model is developed describing the
      transmission of HIV in heterosexual partnerships between African migrants,
      Caribbean migrants, and local natives. The model accounts for infection of
      migrants before migration and during trips to their home country. The model is
      parameterized using data from the Netherlands. RESULTS: Among new and newly
      imported, heterosexually acquired, infections in 2010 in the Netherlands, the
      individual acquiring HIV is an African in 53% of cases, a Caribbean in 26% of
      cases, and a Dutch native in 21% of cases. The percentage of new infections
      acquired outside the Netherlands is 40% among African migrants and 32% among
      Caribbean migrants; these are mostly acquired before migration to the
      Netherlands. The prevalence of HIV in the Netherlands is hardly affected by
      changes in risk behaviour of migrants during trips to their home country after
      migration. If migrants mix more with the Dutch in forming partnerships, then HIV
      prevalence among migrants will decrease. The more initiating antiviral therapy is
      delayed among migrants, the higher the resulting prevalence in their own ethnic
      group and among the Dutch. CONCLUSION: The serostatus of individuals migrating to
      low-prevalence countries as well as their sexual behaviour in the country of
      residence affect considerably the spread of HIV. Preventive measures should focus
      on targeted interventions, promoting safe sex practices, HIV testing, and entry
      to specialized HIV care among migrants.

PMID- 20671544
TI  - Associations of antiretroviral drug use and HIV-specific risk factors with
      carotid intima-media thickness.
AB  - BACKGROUND: Previous research has demonstrated an increase in carotid intima
      media thickness (cIMT) in HIV-infected individuals compared to controls. However,
      the reason for this increased level of subclinical vascular disease is unknown.
      OBJECTIVE: To identify HIV-related risk factors for increased cIMT. METHODS: We
      evaluated the relationship between HIV-related characteristics (including markers
      of HIV disease severity and use of antiretroviral therapy) and cIMT measurements
      in the internal/bulb and common carotid regions among 538 HIV-infected
      participants from the Study of Fat Redistribution and Metabolic Change in HIV
      Infection (FRAM). We used Bayesian model averaging to estimate the posterior
      probability of candidate HIV and non-HIV-related risk factors being true
      predictors of increased cIMT. Variables with a posterior probability of more than
      50% were used to develop a selected regression model for each of the anatomic
      regions. RESULTS: For common cIMT, the Bayesian model selection process
      identified age, African-American race, and systolic and diastolic blood pressure
      with probability more than 95%, HDL cholesterol with probability 85% and Hispanic
      ethnicity with probability 51%. Among the HIV-related factors included in the
      analysis, only tenofovir use was selected (51% probability). In the selected
      model, duration of tenofovir use was associated with lower common cIMT (-0.0094
      mm/year of use; 95% confidence interval: -0.0177 to -0.0010). For internal cIMT,
      no HIV-related risk factors were above the 50% posterior probability threshold.
      CONCLUSION: We observed an inverse association between duration of tenofovir use
      and common carotid cIMT. Whether this association is causal or due to confounding
      by indication needs further investigation.

PMID- 20671546
TI  - Development of optical sensing system for noninvasive and dynamic monitoring of
      thrombogenic process.
AB  - We developed a compact optical sensing system to monitor thrombogenic process
      noninvasively and dynamically by attaching a sensor on a blood circulating
      tubing. The system monitors the process for normal, erythrocyte aggregation,
      emboli, and thrombus formation stages with a continuously measured backscattered
      light. The system consists of an optical sensing unit, which has an 810-nm
      wavelength chip light-emitting diode (LED) and a photodiode, and real-time
      monitoring software. The erythrocyte aggregation is verified by using the
      baseline transition of optical intensity, which is influenced by the apparent low
      number of red blood cells in erythrocyte-aggregated situation. Meanwhile, the
      emboli are evaluated by counting light-detected microembolic signals (LMES)
      induced by the flowing emboli. The performance of the system was evaluated using
      in vitro experiments with eight bovine blood samples. We performed optical
      sensing during thrombogenic process, which was intentionally generated by
      controlling the ratio of sodium citrate and calcium chloride solution. The
      activated whole blood clotting time (ACT) has gradually decreased in the process.
      The optical baseline transition has continuously increased at the beginning.
      After the increasing stopped, the LMES was observed. Finally, we found thrombus
      inside the mock-up circuit. As a result, we confirmed that our system is capable
      of monitoring the thrombogenic process noninvasively and dynamically.

PMID- 20671548
TI  - A MID1 mutation associated with reduced penetrance of X-linked Opitz G/BBB
      syndrome.
AB  - The X-linked Opitz G/BBB syndrome (OS) is a congenital malformation disorder
      characterized by hypertelorism, swallowing difficulties, hypospadias, and
      additional midline malformations. Loss of function mutations in the MID1 gene at
      Xp22.3 are responsible for the X-linked form of OS. Various mutations are found
      all over the gene but without a clear genotype-phenotype correlation. We describe
      additional family studies of a previously reported boy with a relatively mild
      form of OS, caused by the unique p.Lys370Glu (c.1108A>G) mutation in MID1. The
      same mutation was found in his clinically affected brother but also in the
      healthy maternal uncle. To our knowledge, this is the first report of a MID1
      missense mutation causing non-penetrance in a male.

PMID- 20671547
TI  - Protein kinase C isozymes as regulators of sensitivity to and self-administration
      of drugs of abuse-studies with genetically modified mice.
AB  - Studies using targeted gene deletion in mice have revealed distinct roles for
      individual isozymes of the protein kinase C (PKC) family of enzymes in regulating
      sensitivity to various drugs of abuse. These changes in drug sensitivity are
      associated with altered patterns of drug self-administration. The purpose of this
      review is to summarize behavioral studies conducted on mice carrying targeted
      deletions of genes encoding specific PKC isozymes (namely the beta, gamma, delta,
      and epsilon isozymes), and to critically evaluate the possibility of using
      pharmacological inhibitors of specific PKC isozymes as modulators of the
      sensitivity to various drugs of abuse, as well as potential aids in the treatment
      of substance use disorders.

PMID- 20671549
TI  - A de novo unbalanced translocation leading to partial monosomy 9p23-pter and
      partial trisomy 15q25.3-qter associated with 46,XY complete gonadal dysgenesis,
      tall stature and mental retardation.
AB  - Syndromic forms of disorders of sex development constitute a challenge for
      clinical and molecular investigations. We report on a 12-year-old girl presenting
      with lack of pubertal development, tall stature and moderate mental retardation.
      Conventional karyotyping at the age of 3 years revealed a male karyotype (46,XY).
      At the age of 12 years, the girl had no signs of puberty, and laboratory values
      were consistent with hypergonadotropic hypogonadism because of complete gonadal
      dysgenesis. Histology at the time of gonadectomy revealed fibrous tissue without
      testicular morphology. Cytogenetic reevaluation at that time showed additional
      material of unknown origin on the short arm of chromosome 9. Subsequent
      fluorescence in-situ hybridization and Array-CGH analyses revealed an unbalanced
      translocation between 9p and 15q resulting in a partial monosomy of 9p and a
      partial trisomy of 15q. The karyotype was described as
      46,XY,der(9)t(9;15)(p23;q25.3). We discuss the clinical and molecular cytogenetic
      findings with respect to the literature.

PMID- 20671550
TI  - Comparison of a low-osmolar contrast medium, iopamidol, and an iso-osmolar
      contrast medium, iodixanol, in MDCT coronary angiography.
AB  - OBJECTIVE: To prospectively compare iopamidol 370, which is a low-osmolar
      contrast medium and iodixanol 320, which is an iso-osmolar contrast medium, in
      terms of image quality and nonserious adverse effects that have the potential to
      influence the image quality in a 16-slice multi-detector row computed tomography
      coronary angiography. METHODS: Sixty patients were divided into two groups to
      receive iodixanol 320 or iopamidol 370. Image quality was assessed, using a five
      point grading scale. Differences in the mean attenuation (Hounsfield units) at
      the origin of the coronary arteries and on the ascending aorta in both the groups
      were compared. The number and intensity of adverse effects were compared between
      the two groups. RESULTS: The mean attenuation values of the ascending aorta and
      the origins of the coronary arteries for the two groups showed no significant
      difference (P>=0.41). There was no significant difference in terms of image
      quality between the two groups on all evaluated segments. There was a
      statistically significant difference in the number of adverse effects (P=0.001)
      between the two groups. However, in both the iodixanol group and the iopamidol
      group, there was no significant difference in terms of image quality between the
      patients with and without adverse effects. CONCLUSION: The frequency of adverse
      effects is lower in the iodixanol group than the iopamidol group. Iodixanol 320
      can provide both vascular enhancement and image quality, which is similar to
      iopamidol 370 in a 16-slice multi-detector row computed tomography coronary
      angiography. There was no significant difference in terms of overall image
      quality between the patients with and without adverse effects in either of the
      groups.

PMID- 20671551
TI  - The cardiologist and smoking cessation.
AB  - PURPOSE OF REVIEW: Among the modifiable risk factors, smoking contributes
      strongly to the global epidemics of cardiovascular disease morbidity and
      mortality. In patients with cardiovascular disease, the benefits of smoking
      cessation outperform those expected from other preventive strategies such as
      blood pressure or cholesterol control. In-hospital interventions to assist
      cardiovascular disease patients with smoking cessation and to provide adequate
      follow-up are the most cost-effective strategies to improve the survival of the
      cardiovascular patient. RECENT FINDINGS: Data on cardiologists' interest in
      increasing smoking cessation rates are limited and alarming. Surveys assessing
      the knowledge, interest and attitudes of cardiologists regarding smoking
      cessation assistance highlight poor commitment to this important preventive
      practice. For a substantial proportion of cardiologists, smoking-cessation
      assistance is not included in their core activities and they do not consider
      themselves as the most appropriate person for this purpose. Disappointingly, many
      of them never refer their smoking patients to specialized centers and/or teams
      for appropriate assistance. SUMMARY: The substantial benefits of smoking
      cessation in cardiovascular prevention requires stronger commitment from
      cardiologists to provide smoking-cessation therapies and counseling. Further
      research is needed to highlight the barriers to improve clinical performance by
      cardiologists in this field of prevention.

PMID- 20671552
TI  - Right-ventricular function by nuclear cardiology.
AB  - PURPOSE OF THIS REVIEW: Right-ventricular (RV) function has both diagnostic and
      prognostic relevance; thus the ability to accurately evaluate and quantify the RV
      is critical. Nuclear techniques provide an accurate and reproducible assessment
      of RV systolic function. Additionally, nuclear techniques can assess RV
      physiology, thus providing insight into the pathogenesis of common conditions
      affecting the RV. In this review, we describe the role of nuclear imaging in
      assessing RV systolic function, perfusion, and metabolism. RECENT FINDINGS:
      Nuclear techniques to quantify RV function have been available for many years,
      but newer methods to evaluate RV function are emerging. Recent investigations
      into the pathophysiology of RV failure from a variety of causes have identified
      RV ischemia and alterations in RV metabolism as major contributors. Because
      nuclear-imaging techniques also allow evaluation of RV ischemia and metabolism,
      nuclear imaging may allow a comprehensive assessment of RV function and
      physiology. SUMMARY: In addition to providing a reliable determination of RV
      systolic function, nuclear-imaging techniques are emerging as clinically useful
      tools to assess RV perfusion and metabolism. As these novel uses of nuclear
      imaging for RV assessment continue to be studied and validated across a variety
      of clinical settings, an expanded role of nuclear imaging of the RV is
      anticipated.

PMID- 20671553
TI  - Medical management of metastatic bone disease.
AB  - PURPOSE OF REVIEW: To highlight recent advances in the medical management of
      metastatic bone disease. RECENT FINDINGS: Progress has been made in quality of
      life assessment and pain measurement; in novel ways to use bisphosphonates,
      especially in the adjuvant setting for prevention of bone metastases and in
      combination with other pharmaceutical agents, where synergistic enhancement holds
      high potential; in targeted therapies using novel agents, especially with
      denosumab which is approaching registration; in the use of bone biomarkers to
      direct therapy and as surrogate endpoints; in development of radiopharmaceuticals
      for improved treatment of disseminated bone pain. SUMMARY: Metastatic bone
      disease continues to present management challenges, but these challenges are
      being met with an increased armamentarium of available interventions.

PMID- 20671554
TI  - Management of metastatic spine disease.
AB  - PURPOSE OF REVIEW: In metastatic spine disease, technologic advancements,
      neurologic recovery, pain relief, cost-effectiveness, and health-related quality
      of life have all strengthened surgery's and radiation's role in its management.We
      evaluated different surgical approaches to the spine and the multimodality
      treatment in the management of these cases. RECENT FINDINGS: Recently, the
      survival rate of malignant spinal metastases has rapidly improved because of
      early detection and multimodality treatment. The goals of surgical intervention
      are to prolong survival and improve the quality of life of patients.The recent
      evolution of imaging, radiosurgery, advanced surgical decompressive techniques
      and instrumentation, as well as percutaneous vertebral body cement augmentation,
      needs to be considered in the decision-making to optimize patient outcomes.
      SUMMARY: Management of patients with spine tumors requires a multidisciplinary
      team that includes a medical and radiation oncologist and a spine surgeon. Newer
      surgical techniques that address both tumor resection and spinal stabilization
      offer the best outcome in selected patients. The prognostic parameters suggested
      for metastatic spine tumors include the general condition of the patient,
      neurological status number of spinal and extraspinal metastases, primary site of
      the cancer, visceral metastasis, and severity of spinal cord compression.

PMID- 20671555
TI  - Composition of the anaesthesia team: a European survey.
AB  - BACKGROUND AND OBJECTIVE: The anaesthesia workforce in Europe is understaffed and
      may not meet the growing demands of surgery. In many European countries where
      responsibilities can be identified and a varying degree of task substitution
      occurs, the anaesthesia service is provided by a team of physician and
      nonphysician anaesthesia members. This study assesses the availability, as well
      as the roles and functions, of nonphysician anaesthesia team members in European
      countries. METHODS: A survey was carried out to examine differences in
      anaesthesia practices and the strength of the anaesthesia workforce in Europe. A
      questionnaire, seeking information about perioperative anaesthesia input by
      nonphysician anaesthesia team members, was sent to all the national
      representatives of the Union of European Medical Specialists Anaesthesiology
      section and the International Federation of Nurse Anaesthetists. RESULTS: The
      responses to the questionnaire revealed that each European country has its own
      unique type of nonphysician anaesthesia team member and the roles of these vary
      substantially. Their levels of organisation vary from country to country and
      whereas nurse anaesthetists are often well organised, circulation nurses are not.
      CONCLUSION: The present study demonstrated the heterogeneity and variety of
      anaesthesia practices throughout Europe. Standardisation of the training and
      practice of European nurse anaesthetists is desirable for patient safety and
      quality of care if they seek to work in more than one European country. Those
      countries that anticipate a shortfall in the supply of anaesthesiologists should
      examine working models from other countries that currently work with fewer
      physicians and more nurse anaesthetists.

PMID- 20671556
TI  - Ineffectiveness of intralipid infusion for central nervous toxicity following
      ultrasound-guided sciatic nerve block with lidocaine-ropivacaine solution:
      interaction between carbamazepine, local anaesthetic and intralipid?

PMID- 20671557
TI  - Bispectral index monitoring during balanced xenon or sevoflurane anaesthesia in
      elderly patients.
AB  - BACKGROUND AND OBJECTIVE: In the elderly, monitoring depth of anaesthesia seems
      to be of particular importance. We evaluated the bispectral index (BIS) for
      monitoring depth of anaesthesia during clinically guided balanced xenon or
      sevoflurane anaesthesia in aged patients. METHODS: In this randomized controlled
      clinical trial, 40 patients (65-75 years) undergoing elective noncardiac surgery
      were randomly assigned to balanced anaesthesia with either 53.2 +/- 0.8% xenon (n
      = 19) or 1.6 +/- 0.1% sevoflurane (n = 20) in minimum 30% oxygen and remifentanil
      titrated to clinical needs. Depth of anaesthesia was guided by end-tidal gas
      concentrations and clinical signs. The attending anaesthesiologist was blinded to
      the BIS values, which were recorded at 1 min rates during induction, at 5 min
      rates during maintenance and at 20 s rates during emergence. Emergence from
      anaesthesia was assessed by the times to open eyes, react on demand, extubation
      and orientation. RESULTS: During induction and maintenance of anaesthesia, BIS
      values in the xenon group were comparable to sevoflurane and at the lower limit
      of the recommended range for deep anaesthesia. Emergence to full orientation was
      significantly faster from xenon than from sevoflurane. BIS values were
      significantly lower during emergence from xenon anaesthesia. CONCLUSION: During
      xenon and sevoflurane anaesthesia in the elderly, BIS-values show sufficient
      concordance with clinical signs of anaesthetic depth. Since during clinically
      guided anaesthesia values were at the lower recommended limit, additional BIS
      monitoring may help reduce anaesthetic consumption and costs.

PMID- 20671558
TI  - Correlation of central venous-arterial and mixed venous-arterial carbon dioxide
      tension gradient with cardiac output during neurosurgical procedures in the
      sitting position.
AB  - BACKGROUND AND OBJECTIVE: The study was conducted to evaluate the correlation of
      central venous-arterial and mixed venous-arterial pCO(2) gradient with cardiac
      output in patients being operated in the sitting position. METHODS: Fifty-one
      patients, aged 41-69 years, classified as American Society of Anesthesiologists
      physical status II and III, scheduled to undergo elective neurosurgical
      procedures in the sitting position, were enrolled in this prospective cohort
      study. Simultaneous blood gas samples from arterial, central venous and pulmonary
      artery catheters were collected at four different time points during supine and
      sitting position. Cardiac index (CI) determination was accomplished
      simultaneously, with continuous cardiac output technique. The mixed venous
      arterial pCO(2) and central venous-arterial pCO(2) gradients were calculated and
      related to CI at the specific time points, thus a total of 204 points of
      comparison were obtained. RESULTS: Changing from the supine to the sitting
      position induced a significant deterioration of CI, right atrial pressure, mean
      pulmonary arterial pressure and pulmonary wedge pressure. The mean delta pCO(2)
      difference (bias) in the four time points ranged between -0.07 and -0.27. The
      upper (1.59-1.71 mmHg) and lower limits of agreement (-2.16 to -1.82 mmHg) were
      quite narrow, suggesting an acceptable overall agreement between the mixed and
      central venous pCO(2) differences. The coefficient of determination (R(2))
      between the venous-arterial pCO(2) and CI for mixed and central venous
      circulations was 0.830 and 0.760 (P < 0.001 for both), respectively. In contrast,
      R(2) values between mixed and central venous oxygen saturation values and CI were
      0.324 and 0.286, respectively (P < 0.001 for both), illustrating a rather weak
      relationship. CONCLUSION: It seems that venous-arterial pCO(2) values obtained
      from mixed and central venous circulations can be reliably interchanged in
      estimating CI in patients undergoing neurosurgical procedures in the sitting
      position. Thus, central venous-arterial pCO(2) gradient could serve as a useful
      and simple method for estimating cardiac performance, in which further invasive
      monitoring is not strongly indicated.

PMID- 20671559
TI  - Inflammatory bowel disease and pregnancy: report of two cases treated with
      infliximab and a review of the literature.
AB  - Inflammatory bowel disease is relatively frequent in women of childbearing age.
      Disease management requires greater attention during this clinical condition
      because of potential risk of maternal-fetal complications. Infliximab has been
      shown to be safe during pregnancy and lactation, but reports in the literature
      are scarce. We report two cases of refractory Crohn's disease treated with
      infliximab with good results, in women. Both patients became pregnant during
      maintenance regimen and treatment was continued. The literature regarding
      pregnant patients with inflammatory bowel disease was reviewed.

PMID- 20671560
TI  - Inter-rater reliability of the Modified Ashworth Scale and modified Modified
      Ashworth Scale in assessing poststroke elbow flexor spasticity.
AB  - The Modified Ashworth Scale (MAS) is commonly used in clinical practice for
      grading spasticity. However, it was modified recently by omitting grade '1+' of
      the MAS and redefining grade '2'. The aim of this study was to investigate the
      inter-rater reliability of MAS and modified MAS (MMAS) for the assessment of
      poststroke elbow flexor spasticity. Sixty-four patients with poststroke
      hemiplegia were enrolled. The mean age and time since the stroke were 60.5 +/-
      11.9 years and 15.7 +/- 10.2 weeks, respectively. The patients were tested by two
      raters having equal experience in applying MAS. They were not subjected to any
      training for administering MMAS. After performing no more than two test
      movements, the raters graded the resistance felt, according to the MAS and MMAS,
      respectively based on same stretch. The degree of agreement was analyzed using
      the weighted kappa (kw) statistic. Inter-rater agreements were very good for both
      MAS and MMAS, with weighted kappa values of 0.868 and 0.892, respectively. The
      highest agreements were observed for grade '0' in applying MAS and for grade '2'
      in applying MMAS; on the other hand, the lowest agreements were observed for
      grade '2' in applying MAS and for grade '3' in applying MMAS. According to our
      results, MAS and MMAS have very good inter-rater reliability for assessment of
      poststroke elbow flexor spasticity. Neither of the scales is superior to each
      other when using them to grade spasticity in patients with hemiplegia for this
      muscle group.

PMID- 20671561
TI  - Toxic epidermal necrolysis in pregnancy: case report and review of the
      literature.
AB  - The authors report the case of a 29-year-old pregnant woman (2g1p) in the 16th
      week of gestation presenting with extensive toxic epidermal necrolysis (TEN). The
      cutaneous symptoms began at hands, feet, and in the mouth and developed during
      the course of 10 days to cover 75% of her TBSA, whereas total epidermolysis was
      present on more than 40% of her TBSA. Because of progressive swelling and
      bleeding of the oral mucosa, tracheal intubation was necessary to secure the
      airway of the patient. Critical care management required sedation, tracheotomy
      and artificial ventilation (14 days), prolonged fluid resuscitation, daily wound
      care, topical antiseptic and systemic antibiotic medication, hemostatic therapy
      and blood transfusion, hypercaloric nutrition, and frequent obstetric ultrasound
      evaluations. Reepithelialization began simultaneously with progressive
      epidermolysis and was completed after 35 days of conservative treatment. Because
      the patient experienced a swollen vulva and a stenotic birth channel, typical
      sequelae of TEN, a primary cesarean section was required after 40 weeks of
      gestation. The male infant showed neither signs of skin detachment nor sequelae
      caused by the prolonged therapy for the mother. A multidisciplinary approach and
      appropriate medical infrastructure are required to solve the challenge of TEN in
      pregnancy. In addition, the particular role of gestation in the pathophysiology
      of TEN needs to be explored further.

PMID- 20671562
TI  - Guided surgical debridement: staining tissues with methylene blue.
AB  - Precise surgical debridement of wounds is required to achieve wound closure. The
      authors describe their experience with a technique using topical methylene blue
      to facilitate precise surgical debridement. In this technique, methylene blue dye
      is applied topically to the wound surface at the onset of surgery. The stained
      wound site is then wiped to remove dye from the surface of normal epithelium;
      eschar, nonviable tissue, and granulation tissue remain stained. The methylene
      blue-stained tissue is surgically removed, and the newly debrided surface of the
      wound is assessed for adequate vascularity and biopsied to verify presence of
      bacteriologic balance before closure. The authors have used this technique in
      more than 200 wound debridements during the past year, including acute surgical
      or traumatic wounds, acute and subacute burn wounds, chronic granulating wounds,
      partially epithelialized wounds, sinus tracts, and fistulae. No adverse reactions
      have been noted, even on patients undergoing multiple applications through serial
      operations. Topical application of methylene blue to wounds with mixed tissue
      content helps to distinguish between viable and nonviable tissue and between
      epithelialized and nonepithelialized areas, facilitating more precise and
      complete wound debridement.

PMID- 20671563
TI  - The use of immunonutrition in burn injury care: where are we?
AB  - The aim of this study is to review the current evidence for immunonutrition use
      in patients with burn injury. Nutrients of interest included glutamine, arginine,
      and omega-3 fatty acids (fish oil). A literature review was conducted to identify
      studies that evaluated the use of immunonutrients in pediatric and adult patients
      with burn injury. Search terms included burns, immunonutrition,
      pharmaconutrition, glutamine, arginine, omega-3, and fish oil. Glutamine: Nine
      randomized controlled trials (four represented in abstract only) investigating
      enteral supplementation and two trials investigating parenteral supplementation
      of glutamine were identified. Arginine: Five trials investigating the effect of
      arginine supplementation were identified (three represented in abstract only).
      Omega-3 fatty acids: Three studies investigating the effect of enteral fish oil
      supplementation were identified (one represented in abstract only). Combined
      immunonutrients: Six studies were identified that investigated immunonutrients as
      a combination of active dietary constituents (rather than as individual
      nutrients). Despite the semiessential nature of arginine after burn injury, there
      were surprisingly little data regarding nutritional supplementation. Literature
      around supplementation of omega-3 fatty acids is found to be lacking in the burn
      injury population. The combination of immunonutrients as a component of enteral
      formulae limits identification of the active nutrient and ideal dosage. Current
      evidence supports the use of enteral glutamine supplementation for patients with
      severe burn injuries. Questions remain regarding dosage, timing, and length of
      supplementation.

PMID- 20671564
TI  - Pilot testing of a multicomponent home care intervention for older adults with
      heart failure: an academic clinical partnership.
AB  - BACKGROUND: Heart failure (HF) has clinically significant psychological and
      physical consequences for older persons, and hospitalization for HF is frequent
      and costly to the Medicare program. As HF is the most common primary Medicare
      home care diagnosis, there is a critical need to develop home care services that
      improve heath-related outcomes for this population. The primary aim of this pilot
      study was to develop, implement, and test the initial feasibility and potential
      efficacy of the Home-Care Education, Assessment, Remote-Monitoring, and
      Therapeutic Activities (HEART) trial, a nurse-directed multicomponent home care
      intervention. Observed outcomes were quality of life (QOL), depressive symptoms,
      and 90-day hospitalization. METHODS: Twenty-four patients with a primary
      diagnosis of HF were assigned to the intervention (n = 12) or control group (n =
      12) according to geographical location in a large multibranch Medicare-certified
      home health agency. Intervention group patients received 8 structured nurse
      education visits using evidence-based protocols designed in previous trials to
      teach HF self-management and to prevent/reduce depression, as well as a
      telemonitoring system. Control group patients received usual care and
      telemonitoring. Quality of life was assessed using the Minnesota Living With
      Heart Failure questionnaire. Depressive symptoms were assed using the Patient
      Health Questionnaire 9 at baseline and 90-day study end point. RESULTS: Study
      protocols and instrumentation were found to be feasible and effective.
      Examination of enrollment data led to a reevaluation of eligibility criteria.
      Patients participating in the HEART intervention demonstrated significantly
      improved QOL (F = 8.99, P = .007) and significantly reduced depressive symptoms
      (F = 35.10, P = .001) in comparison to control group patients at the study end
      point. There was a trend toward lower hospital readmission rates in the
      intervention group (16% vs 25%), but this was not statistically significant.
      CONCLUSION: This pilot study suggests that a full-scale trial of the HEART
      intervention is feasible.

PMID- 20671565
TI  - Determinants of global perceived health in community-dwelling elderly screened
      for heart failure and sleep-disordered breathing.
AB  - The relationships between heart failure (HF), sleep-disordered breathing (SDB),
      insomnia, depressive symptoms, and excessive daytime sleepiness (EDS), as well as
      their relationship to Global Perceived Health (GPH) in an elderly community
      dwelling population, have not been explored. Data from 331 community-dwelling
      elderly (71-87 years old) were collected by echocardiography, polygraphy, and
      specific questionnaires. Factor analyses and structural equation modeling were
      used to explore the relationships between HF, SDB, sleep, psychosocial factors,
      and GPH. Exploratory and confirmatory factor analyses derived a 5-factor model
      representing SDB, insomnia, systolic function, breathlessness/physical function,
      and psychosocial function. Structural equation modeling analyses were used to
      explore the relationships between the 5 factors and to GPH. Sleep-disordered
      breathing had a weak effect on systolic function, but no effects on any of the
      other factors or GPH were found. Psychosocial function and
      breathlessness/physical function directly affected GPH. Indirect effects on GPH,
      mediated by psychosocial function, were found for breathlessness/physical
      function and insomnia. Systolic function also had an indirect effect on GPH. The
      fact that SDB in the elderly has no obvious negative associations to sleep
      complaints or GPH does not exclude them from being adequately treated for SDB.
      However, the present study has shown that SDB, by means of self-rated sleep
      complaints and health-related quality of life, can be problematic to detect.
      Psychosocial function was the most important factor for perceived GPH as it had a
      direct effect, as well as mediated the factors breathlessness/physical function
      and insomnia effects, on GPH. This study indicates that interventions in clinical
      practice targeting psychosocial dysfunction, such as depressive symptoms, could
      help to improve GPH in the elderly with or without HF.

PMID- 20671566
TI  - Beware of the dog: a case report on cardiac involvement in drug allergy.

PMID- 20671567
TI  - Heart failure therapy: beyond the guidelines.
AB  - Heart failure is a chronic and debilitating disease responsible for high cardiac
      morbidity and mortality in the world and is associated with over 290 000 deaths
      in the United States each year. This article reviews palliative care and self
      care, which are critical components of heart failure management that are
      inadequately defined in the current American College of Cardiology/American Heart
      Association Guidelines for the Diagnosis and Management of Heart Failure.
      Palliative care describes a multidisciplinary approach to the treatment of heart
      failure therapy that addresses both the symptomatic and psychosocial aspects of
      the disease. Self-care aims to maintain disease stability and prevent clinical
      decline through a variety of patient-based behavioral and lifestyle
      modifications.

PMID- 20671568
TI  - Hyperkalemia-induced conversion of permanent atrial fibrillation to normal sinus
      rhythm: a case report.

PMID- 20671569
TI  - Complete resolution of very late stent thrombosis with systemic thrombolysis.

PMID- 20671570
TI  - Complete fracture and migration of a coronary sirolimus-eluting stent.

PMID- 20671571
TI  - Elevation of QT dispersion after obesity drug sibutramine.
AB  - BACKGROUND: QT dispersion (QTd) is an arrhythmia parameter that can be used to
      assess homogeneity of cardiac repolarization. An antiobesity drug sibutramine is
      linked with several cardiovascular adverse events, including arrhythmias.
      Previous studies showed that sibutramine may prolong the QT interval and may be
      associated with cardiac arrest. OBJECTIVES: The aim of this study was to evaluate
      the effect of sibutramine on QTd. METHODS: The study group consisted of 65
      consecutive patients with obesity. All patients were to receive 15 mg of
      sibutramine once a day in addition to standard care for lifestyle change. Twelve
      lead ECG was performed before the onset of the medication and after 16 weeks of
      treatment. QTd was calculated. RESULTS: Three individuals were withdrawn from the
      study because of the adverse effects of sibutramine. Sixty-two patients with
      obesity were recruited into the study. All patients were women (62, 100%). Body
      weight (106.3 +/- 15.0 kg vs. 101.6 +/- 16.9 kg, P < 0.001) and low-density
      lipoprotein cholesterol (128.4 +/- 29.7 mg/dl vs. 111.6 +/- 24.6 mg/dl, P <
      0.001) levels were significantly decreased whereas QTd (46.1 +/- 22.6 ms vs. 53.7
      +/- 16.7 ms, P = 0.026) was significantly increased after 16 weeks of sibutramine
      treatment. The increase in QTd was not correlated with the decrease in body
      weight. There was no correlation between QTd and any conditions such as diabetes
      or hypertension. CONCLUSION: This study has shown an elevation in QTd, which may
      lead to cardiac arrhythmias, after sibutramine treatment. Molecular mechanisms
      may play role in increasing QTd. Further randomized studies are needed to clarify
      cardiac adverse events of the sibutramine.

PMID- 20671572
TI  - Serve and surgery: type A acute aortic dissection CT imaging resembling a tennis
      ball.

PMID- 20671573
TI  - Isolated native tricuspid valve endocarditis due to group A beta-hemolytic
      Streptococcus without drug addiction.
AB  - We discuss a case of tricuspid valve endocarditis to group A Streptococcus in a
      middle-age man without a history of intravenous drug use. 

PMID- 20671574
TI  - Stent thrombosis and Kounis syndrome: who is guilty?

PMID- 20671575
TI  - Multislice computed tomography demonstration of a coronary-to-pulmonary artery
      fistula.

PMID- 20671576
TI  - Quercetin-6-C-beta-D-glucopyranoside isolated from Ulmus wallichiana planchon is
      more potent than quercetin in inhibiting osteoclastogenesis and mitigating
      ovariectomy-induced bone loss in rats.
AB  - OBJECTIVE: The aim of this study was to determine the skeletal effect of
      quercetin-6-C-beta-D-glucopyranoside (QCG) isolated from the extract of Ulmus
      wallichiana and compare this effect with quercetin (Q) in a rat model of
      postmenopausal bone loss. METHODS: Murine bone marrow cells were used to study
      the effect of QCG or Q on osteoclast differentiation. QCG or Q (1.0 and 5.0 mg
      kg(-1) d(-1) doses) was administered orally to ovarietomized (OVx) rats for 12
      weeks. Sham-operated + vehicle and OVx + vehicle groups served as positive and
      negative controls, respectively. Bone mineral density, bone microarchitecture,
      biomechanical strength, bone turnover markers, and uterotrophic effect were
      studied. One-way analysis of variance was used to test significance of effects.
      RESULTS: QCG at 1.0 nM significantly inhibited differentiation of multinucleated
      osteoclasts and expression of osteoclastogenic genes from bone marrow cells,
      whereas Q at 10.0 MUM had comparable results. OVx rats treated with QCG exhibited
      significantly higher bone mass and better microarchitecture in trabecular and
      cortical bones compared with OVx + vehicle. QCG treatment of OVx rats had better
      functional impact than did Q-treated OVx rats, evident from increased bone
      biomechanical strength. Serum osteocalcin and urinary fragments of type 1
      collagen were significantly lower in QCG-treated OVx rats compared with OVx +
      vehicle group. The protective effect of QCG under ovariectomy-induced bone loss
      setting was found to be significantly better than Q. Uterine histomorphometry
      parameters of OVx rats did not change with QCG treatment. CONCLUSIONS: QCG
      improves bone biomechanical quality more effectively than Q through positive
      modifications of bone mineral density and bone microarchitecture without a
      hyperplastic effect on the uterus.

PMID- 20671577
TI  - The association of breast disease and atypical glandular cells on cervical
      cytology.
AB  - OBJECTIVE: This study seeks to determine whether an association exists between
      atypical glandular cells (AGC) on cervical cytology and breast disease. METHODS:
      We analyzed 470,147 Papanicolaou test results from January 1, 2002, to November
      17, 2008, inclusive. We studied all cases of AGC versus a control group with
      normal Papanicolaou test results. The database was then searched to determine
      which of these women had a history of breast disease. A comparison of the
      prevalence of breast disease between the two groups was performed. RESULTS: Of
      the 470,147 total Papanicolaou tests, 1,087 cases of AGC (0.23%) were identified
      from 1,026 women. There were 1,064 women comprising the normal population. The
      mean +/- SD age of these two groups was 44.9 +/- 13.7 and 41.6 +/- 14.4 years,
      respectively. Among the women with an AGC on Papanicolaou testing, 40 (3.9%) had
      breast disease compared with 21 (2.0%) among those without an AGC on Papanicolaou
      testing (P = 0.009). Among the 40 women with an AGC on their Papanicolaou test
      and breast disease, 7 (17.5%) also had a concerning gynecologic (Gyn) pathologic
      finding at the level of the cervix, endocervix, or uterus. In comparison, the
      women with normal Papanicolaou test results had no Gyn pathologic findings.
      CONCLUSIONS: The prevalence of an abnormal Gyn pathologic finding in those with
      AGC is consistent with prior data. Women from this data set who have an AGC on
      Papanicolaou testing have a statistically higher likelihood of having concurrent
      breast disease. Further data are needed to elucidate the reason for this
      association.

PMID- 20671578
TI  - Written words supersede pictures in priming semantic access: a P300 study.
AB  - The dynamic interplay of semantic access during information integration across
      the verbal and nonverbal domains and sensory modalities is poorly understood.
      Here, we compared the priming effects of four types of meaningful stimuli
      (pictures, written words, spoken words, and environmental sounds) on picture and
      written word targets referring to the same concept in all cases. P3b event
      related brain potentials indexed automatic access to semantic memory in the
      different modalities. As expected, P3b amplitudes were large in the repetition
      priming condition, but also for word-picture and picture-word visual stimulus
      pairs. Critically, written word primes resulted in the largest P3b amplitudes
      whether elicited by written word or picture targets, suggesting a semantic
      priming supremacy of written words.

PMID- 20671579
TI  - Are 3-to-8-year-old children with Williams syndrome good word-learners?
AB  - This study investigated the phonetic processing of new words in 3-to-8-year-old
      children with Williams syndrome (WS). Word-learning abilities were evaluated with
      a task involving the learning of two phonetically similar words for two different
      objects. Overall, children with WS were able to process fine phonetic details
      while establishing new word-object links. Their performance pattern was predicted
      by their mental age and was characterized by an asymmetrical processing of
      consonant and vowel information to the advantage of consonants found with this
      task in younger, typically developing, children. These results show delayed but
      relatively preserved word-learning abilities in WS, and this trajectory is
      discussed in comparison with typical development.

PMID- 20671580
TI  - Endogenous radial glial cells support regenerating axons after spinal cord
      transection.
AB  - During the development of central nervous system, radial glial cells support
      target-specific neuronal migration. We recently reported that after implantation
      of chitosan channels with complete spinal cord transection, the tissue bridging
      the spinal cord stumps contained axons and radial glial cells. The purpose of
      this study was to clarify the role of the radial glial cells in the tissue
      bridges. Chitosan channels were implanted in rats with thoracic spinal cord
      transection. After 14 weeks, all animals had tissue bridges in the channels that
      contained many radial glial cells in longitudinal arrangement, some of which were
      in contact with axons in the bridges. We suggest that radial glial cells can
      guide regenerating axons across the bridge in the channel after spinal cord
      transection.

PMID- 20671581
TI  - Functional lung assessment with radionuclides in paediatric respiratory diseases:
      a useful, underutilized test in nuclear medicine?
AB  - Ventilation/perfusion (VQ) studies have a much wider application range in
      paediatrics compared with the adult population and provide a noninvasive way to
      evaluate lung function. VQ studies can be used to determine lung function in
      patients with primary lung, vascular, cardiac and skeletal pathology. We have
      examined the literature regarding the current indications of the VQ scan in
      children. We report a summary of the current indications of VQ scans in
      paediatrics corroborated by our own experience as a paediatric tertiary referral
      centre.

PMID- 20671582
TI  - Allostatic load and delirium in the hospitalized older adult.
AB  - BACKGROUND: Delirium is a state of acute confusion and is common in hospitalized
      older adults. Risk factors for delirium have been described; however, less
      clearly defined are the pathophysiological mechanisms that lead to the
      development of delirium. OBJECTIVES: The purpose of this study was to investigate
      the relationship of allostatic load (AL), a cumulative measure of physiological
      dysregulation resulting from adaptation to acute and chronic stress, and delirium
      in the hospitalized older adult. METHOD: In this descriptive study, participants
      65 years and older admitted to the hospital were included. Participants were
      excluded if they had severe cognitive dysfunction or had prevalent delirium. Ten
      parameters reflecting physiological activity across a range of regulatory systems
      were measured on admission. Separate scores were calculated for primary mediators
      and secondary outcomes, subsets of overall AL. Incident delirium was assessed 48
      to 72 hours after admission. RESULTS: Mean age was 75.7 years (range = 66 to 93
      years). The incidence of delirium was 29%. The AL score derived from primary
      mediators, urinary cortisol, epinephrine and norepinephrine, and serum
      dehydroepiandrosterone sulfate predicted the incidence of delirium (odds ratio =
      2.54, 95% confidence interval = 1.12-5.79, p < .05). The overall AL score, the
      score derived from secondary outcomes, and the individual AL measures were not
      related significantly to the incidence of delirium. DISCUSSION: AL has been shown
      to be an important construct in the early identification of physiological
      dysfunction related to exposure to psychosocial and environmental stress. The
      findings from this study suggest that AL, particularly the primary mediators
      score, may be a useful measure in determining delirium risk in hospitalized older
      adults, leading to improved surveillance and prevention of delirium. A better
      understanding of AL may lead to interventions focused on reducing the impact of
      AL on the older adult's physiological function.

PMID- 20671583
TI  - Shared risk factors for distinct geriatric syndromes in older Taiwanese
      inpatients.
AB  - BACKGROUND: Identifying shared common risk factors of geriatric syndromes is
      clinically useful in designing a unified approach to optimizing geriatric care.
      OBJECTIVES: The purpose of this study was to identify older Taiwanese inpatients'
      common shared risk factors among seven distinct geriatric syndromes:
      malnutrition, depression, cognitive impairment, functional dependence,
      incontinence, pressure ulcers, and dehydration. METHOD: A cross-sectional,
      hospital-wide survey was conducted to enroll inpatients (N = 455) older than 65
      years and admitted to 24 medical and surgical units in a 2,200-bed urban academic
      medical center in northern Taiwan. Malnutrition was defined as a Mini-Nutritional
      Assessment score less than 17.5, depression was defined as a Geriatric Depression
      Scale score more than 10, cognitive impairment was considered a Mini-Mental State
      Examination score less than 20, and functional dependence was defined as a
      Barthel Index score less than 50. Incontinence, pressure ulcers, and dehydration
      were extracted from patients' medical records. RESULTS: Participants had a mean
      age of 75.3 years (SD = 6.1 years, range = 65-92 years). The prevalence of
      geriatric syndromes ranged from 5% (pressure ulcers) to 33% (malnutrition). The
      selected geriatric syndromes were shown through logistic regression analysis to
      be predicted by female gender (odds ratio [OR] = 1.57-2.75), functional status
      (OR = 0.94-0.99), cognitive status (OR = 0.82-0.95), nutritional status (OR =
      0.74-0.93), and depressive symptoms (OR = 1.07-1.26), supporting the notion of
      shared risk factors in geriatric syndromes. CONCLUSIONS: The findings support the
      theory that common geriatric syndromes have a shared set of risk factors-female
      gender, depressive symptoms, and functional, cognitive, and nutritional status.
      Revising care to target these shared risk factors in preventing common geriatric
      syndromes is theoretically sound.

PMID- 20671584
TI  - Toll-like receptor 4 gene polymorphisms show no association with the risk of
      clinical or angiographic restenosis after percutaneous coronary intervention.
AB  - OBJECTIVE: Restenosis after percutaneous coronary intervention (PCI) remains an
      issue even in the drug-eluting stent era. Genetic polymorphisms may provide
      insight in the pathogenesis of restenosis and may help in the stratification of
      patients at risk for restenosis. The aim of this study was to examine whether
      polymorphisms at the toll-like receptor 4 (TLR4) locus, that are associated with
      impaired innate immune system and with an increased risk of cardiovascular
      events, were associated with clinical and/or angiographic restenosis after PCI.
      METHODS: The GENetic Determinants of Restenosis (GENDER) project was a
      prospective, multicenter study that enrolled 3146 consecutive patients after
      successful PCI. Frequencies of the TLR4 896A/G (Asp299Gly; rs4986790) and 1196C/T
      (Thr399Ile; rs4986791) polymorphisms and haplotypes were assessed. Patients were
      followed up for 1 year and in a subgroup of 406 patients angiographic follow-up
      was obtained. RESULTS: We included a total of 2682 patients that underwent
      successful PCI. There was no association between genotypes and the risk of target
      vessel revascularization at 1-year or late luminal loss at 6-months angiographic
      follow-up (P=0.53 and 0.44, respectively). Absence of association with target
      lesion revascularization and late luminal loss was replicated in the GEnetic risk
      factors for In-Stent Hyperplasia study Amsterdam (GEISHA) cohort study of 674
      patients and in a subgroup of 550 patients with angiographic follow-up available
      (P=0.26, and 0.86, respectively). Moreover, in both the studies, no significant
      differences between haplotypes A/C and G/T were observed for target vessel
      revascularization at late luminal loss. CONCLUSION: Although inflammation has
      been implicated in the pathophysiology of restenosis, the 896A/G and 1196C/T
      polymorphisms or haplotypes based on these polymorphisms at the TLR4 locus are
      not associated with an increased risk of target vessel revascularization or
      angiographic restenosis after PCI. These polymorphisms are not useful for pre-PCI
      identification of patients at risk for restenosis.

PMID- 20671585
TI  - Association of LOC387715 A69S genotype with visual prognosis after photodynamic
      therapy for polypoidal choroidal vasculopathy.
AB  - PURPOSE: To investigate whether there is an association of the LOC387715 A69S
      genotype with visual prognosis after photodynamic therapy in eyes with polypoidal
      choroidal vasculopathy (PCV). METHODS: Photodynamic therapy was repeated every 3
      months until the disappearance of angiographic signs of active lesions in 71 eyes
      of 71 patients with PCV who were followed-up for at least 12 months. All patients
      were genotyped for LOC387715 A69S polymorphism (rs10490924, risk-allele T).
      RESULTS: Although there was no statistically significant difference in the mean
      baseline visual acuity (P = 0.53) among the 3 genotypes, there was a
      statistically significant difference in the visual acuity both at the 12-month
      and final visits (P = 0.002 and P < 0.001, respectively) with the poorer acuity
      in patients with the higher "T-"allele frequency. "T" allele was more frequently
      observed in those with the recurred PCV lesions (odds ratio: 5.8, 95%
      confidential interval: 2.3-15.1, T vs. G). CONCLUSION: There is a pharmacogenetic
      association between the LOC387715 A69S variant and the long-term results after
      photodynamic therapy in eyes with PCV. The LOC387715 A69S genotype is of clinical
      importance to predict the visual prognosis after photodynamic therapy in eyes
      with PCV. These results should be confirmed or refuted by replication studies.

PMID- 20671586
TI  - Side illumination for internal limiting membrane peeling without staining in
      macular surgery.

PMID- 20671587
TI  - Macular telangiectasia: patterns of distribution of macular pigment and response
      to supplementation.
AB  - PURPOSE: By analyzing the patterns of macular pigment (MP) in type 2 idiopathic
      telangiectasia eyes, different stages in the changes reflecting the extent of
      disease can be observed. The purpose of this study was to determine whether the
      amount and the pattern of MP can be influenced by supplementation. METHOD: Eleven
      patients with type 2 idiopathic telangiectasia received 12 mg lutein and 0.6 mg
      zeaxanthin (Ocuvite Lutein AMD) daily for 9 months. For a period of 12 months, MP
      concentration was determined every 3 months by autofluorescence (2 excitation
      wavelengths: 488 and 514 nm). RESULTS: When central accumulation of MP was
      similar to that in healthy subjects (with segment of reduced MP in the temporal
      fovea: MP Class I), supplementation enriched the MP at 0.5 degrees, 2 degrees,
      and 5 degrees to 6 degrees. In MP Class II (reduced concentration of MP
      centrally), accumulation could be detected at 2 degrees and 5 degrees to 6
      degrees but not centrally. In MP Class III (oval-shaped effacement of MP
      centrally, surrounding oval-shaped ring of MP at 5 degrees-7 degrees
      eccentricity), supplementation promoted MP accumulation only at 5 degrees to 6
      degrees. CONCLUSION: After oral supplementation with lutein/zeaxanthin, an
      increase in the MP was detected only in areas where the MP was present at
      baseline. Supplementation did not produce an increase in the area where the MP
      was absent. Degenerative processes causing an impairment in transport and storage
      of lutein and zeaxanthin may play a leading role in the pathogenesis of type 2
      idiopathic telangiectasia.

PMID- 20671588
TI  - Bone mineral densities of the vertebral body and intertransverse fusion mass
      after instrumented intertransverse process fusion.
AB  - STUDY DESIGN: We used dual-energy x-ray absorptiometry to examine the bone
      mineral densities (BMDs) of the vertebral bodies at the fused level (the fused
      vertebral BMDs), at the unfused level (the unfused vertebral BMDs), and the
      intertransverse fusion mass (the fusion mass BMD) after instrumented
      intertransverse process fusion. OBJECTIVE: We wanted to determine whether there
      are any relationships among the unfused vertebral BMDs, the fused vertebral BMD,
      and the fusion mass BMD after successful solid union. SUMMARY OF BACKGROUND DATA:
      Device-related vertebral osteoporosis is a well-known phenomenon that occurs in
      an early adaptive phase after instrumented spinal fusion. However, any
      relationships among the unfused vertebral BMDs, the fused vertebral BMD, and the
      fusion mass BMD in a later phase after obtaining successful spinal union are
      unknown. METHODS: This study included 17 female patients, who had a solid union
      after instrumented intertransverse process fusion at the L4-L5 level. The average
      patient age at the time of this study was 54 years (range: 46-69 years). The
      vertebral BMDs at the fused level (L4), the vertebral BMDs at the unfused levels
      (L1-L3), and the fusion mass BMD were measured at a mean follow-up period of 42
      months (range: 24-131 months) after surgery. The reciprocal correlations among
      the vertebral BMDs and the fusion mass BMD were analyzed. RESULTS.: The vertebral
      BMDs (g/cm) at the fused level (L4), the unfused level (L1-L3), and the fusion
      mass BMD were 0.84 +/- 0.27, 0.72 +/- 0.23, 0.56 +/- 0.19, 0.58 +/- 0.21, and
      0.54 +/- 0.16, respectively. There were significant reciprocal correlations among
      the vertebral BMDs at the fused and unfused level. However, the fusion mass BMD
      had no significant correlations with any of the vertebral BMDs. CONCLUSION: The
      vertebral bodies at the fused level may undergo osteoporosis in a pattern similar
      to what naturally occurs in the vertebral bodies at the unfused level. However,
      the fusion mass BMD seems to be influenced by bone remodeling mechanisms that are
      different from those that influence the vertebral bodies.

PMID- 20671589
TI  - Qualitative grading of severity of lumbar spinal stenosis based on the morphology
      of the dural sac on magnetic resonance images.
AB  - STUDY DESIGN: Retrospective radiologic study on a prospective patient cohort.
      OBJECTIVE: To devise a qualitative grading of lumbar spinal stenosis (LSS), study
      its reliability and clinical relevance. SUMMARY OF BACKGROUND DATA: Radiologic
      stenosis is assessed commonly by measuring dural sac cross-sectional area (DSCA).
      Great variation is observed though in surfaces recorded between symptomatic and
      asymptomatic individuals. METHODS: We describe a 7-grade classification based on
      the morphology of the dural sac as observed on T2 axial magnetic resonance images
      based on the rootlet/cerebrospinal fluid ratio. Grades A and B show cerebrospinal
      fluid presence while grades C and D show none at all. The grading was applied to
      magnetic resonance images of 95 subjects divided in 3 groups as follows: 37
      symptomatic LSS surgically treated patients; 31 symptomatic LSS conservatively
      treated patients (average follow-up, 2.5 and 3.1 years); and 27 low back pain
      (LBP) sufferers. DSCA was also digitally measured. We studied intra- and
      interobserver reliability, distribution of grades, relation between morphologic
      grading and DSCA, as well relation between grades, DSCA, and Oswestry Disability
      Index. RESULTS: Average intra- and interobserver agreement was substantial and
      moderate, respectively (k = 0.65 and 0.44), whereas they were substantial for
      physicians working in the study originating unit. Surgical patients had the
      smallest DSCA. A larger proportion of C and D grades was observed in the surgical
      group. Surface measurements resulted in overdiagnosis of stenosis in 35 patients
      and under diagnosis in 12. No relation could be found between stenosis grade or
      DSCA and baseline Oswestry Disability Index or surgical result. C and D grade
      patients were more likely to fail conservative treatment, whereas grades A and B
      were less likely to warrant surgery. CONCLUSION: The grading defines stenosis in
      different subjects than surface measurements alone. Since it mainly considers
      impingement of neural tissue it might be a more appropriate clinical and research
      tool as well as carrying a prognostic value.

PMID- 20671590
TI  - Concurrent measurement of isokinetic muscle strength of the trunk, knees, and
      ankles in patients with lumbar disc herniation with sciatica.
AB  - STUDY DESIGN: A cross-sectional study comparing normal subjects and patients with
      lumbar disc herniation (LDH) with sciatica. OBJECTIVE: To simultaneously measure
      the isokinetic muscle strength of the trunk, knees, and ankles in both groups.
      SUMMARY OF BACKGROUND DATA: Coordination between the trunk and lower extremity
      muscles is important for normal physical activity. Reduced trunk and knee muscle
      strength have been reported in patients with lower level LDH; however, ankle
      performance in these patients is still unknown. METHODS: We recruited 43 normal
      subjects as controls and 33 patients with lower level LDH with sciatica. The
      isokinetic strength of the trunk, knees, and ankles was measured at 2 velocities
      in random order: 60 degrees /s and 120 degrees /s, and 60 degrees /s and 180
      degrees /s for trunk and ankle strength and for knee strength, respectively.
      RESULTS: The isokinetic trunk strength was significantly lower in the LDH group
      irrespective of test modes or velocity. Despite unilateral sciatica or test modes
      and velocity, the unilateral knee strength was significantly lower in the LDH
      group than that in the control group. Knee extension torque was also found to be
      significantly lower in the limbs with sciatica than in those without sciatica at
      the testing velocity of 180 degrees /s (80.25 +/- 24.88 vs. 95.42 +/- 26.29 Nm, P
      < 0.05). Irrespective of unilateral sciatica or test velocity, ankle plantar
      flexion torque revealed to be significantly lower in the LDH group than the
      control group; however, dorsiflexion torque was not different. Significant
      correlations were demonstrated among the total muscle strength of the trunk,
      knees, and ankles in both groups. CONCLUSION: Besides the lower trunk strength,
      concurrent lower unilateral knee and ankle plantar flexion but not dorsiflexion
      strength was demonstrated in the LDH subjects with unilateral sciatica,
      regardless of its location. As compared to the limbs without sciatica, an
      additional 14% reduction of knee extension torque at 180 degrees /s was found in
      the limbs with sciatica in the LDH patients.

PMID- 20671591
TI  - Nonfusion method in thoracolumbar and lumbar spinal fractures.
AB  - STUDY DESIGN: a retrospective study of surgically managed patients. OBJECTIVE: to
      evaluate the results of posterior stabilization of thoracolumbar fracture using
      nonfusion method followed by the removal of metal implants within an appropriate
      period. Changes in the sagittal alignment and the restoration of segmental motion
      were also investigated. SUMMARY OF BACKGROUND DATA: posterior fusion using a
      transpedicular screw system remains the treatment of choice for the management of
      thoracolumbar and lumbar fractures. However, fusion methods result in the
      permanent loss of segmental motion. If both stability and motion could be
      achieved, functional results would improve considerably. METHODS: twenty-three
      patients under 40 years of age (mean, 28.0 years) with thoracolumbar or lumbar
      spine fractures were managed by this nonfusion method. Implants were removed at a
      mean 9.7 months after initial fracture fixation, and patients were observed for
      more than 18 months. Sagittal alignments of metal fixed segments, heights of
      vertebral bodies, recovered motion ranges in flexion/extension, right-left
      bending view were measured radiologically. Clinical aspects, such as gross
      deformities and functional abilities, were also investigated. RESULTS: heights of
      fractured bodies were well maintained at final follow-up. Initial mean sagittal
      angle was 17.2 degrees  kyphosis, which became 2.8 degrees  lordosis after
      fixation of fractures. This angle was 1.7 degrees  kyphosis just before implant
      removal, 2.4 degrees  kyphosis just after implant removal, and showed 5.9 degrees
      kyphosis at final follow-up. Mean segmental motion was 14.2 degrees  in the
      sagittal plane and 13.1 degrees  in the coronal plane at final follow-up. Most
      patients were satisfied with final gross appearance and functional outcome.
      CONCLUSION: the described nonfusion method appears to be effective in achieving
      favorable sagittal alignment and regaining motions of fixed segments. The present
      study suggests that the nonfusion method is one of the most effective methods for
      managing thoracolumbar fractures, especially in young active people.

PMID- 20671592
TI  - Age-related variation in cell density of human lumbar intervertebral disc.
AB  - STUDY DESIGN: changes in cell density of endplate (EP), nucleus pulposus (NP),
      and anulus fibrosus (AF) during ageing were systematically investigated in
      defined regions of interest in complete human motion segments. OBJECTIVES: to
      elucidate cell density and total cell number in distinct anatomic regions of the
      intervertebral disc; to test effects of gender, level and age on cell density;
      and to correlate changes in cell density with histologic signs of disc
      degeneration. SUMMARY OF BACKGROUND DATA: the available information on the cell
      density within intervertebral discs and its age-related changes is sparse. This
      knowledge, however, is a crucial prerequisite for cell-based tissue engineering
      approaches of the intervertebral disc. METHODS: in 49 complete cross-sections
      from lumbar motion segments (newborn to 86 years) from 22 specimens, cell density
      was determined by the Abercrombie method in EP, NP, and AF, and total cell number
      was counted per region of interest. RESULTS: cell density in EP, NP, and AF
      decreased significantly from 0 to 16 years with the main changes occuring from 0
      to 3 years for NP and AF. No significant variations were observed thereafter. We
      found a significant correlation of cell density and histologic degeneration score
      between 0 and 1, but not for scores >1. Gender and disc level did not influence
      cell density. CONCLUSION: This study provides data concerning the total number of
      cells in the various regions of the intervertebral disc for different age groups.
      This knowledge will be beneficial for cell-based treatment approaches, which may
      evolve in the future.

PMID- 20671593
TI  - Pleiotropic effects of transforming growth factor-beta in hematopoietic stem-cell
      transplantation.
AB  - Transforming growth factor (TGF)-beta is a pleiotropic cytokine with beneficial
      and detrimental effects posthematopoietic stem-cell transplantation. TGF-beta is
      increased in specific sites postengraftment and can suppress immune responses and
      maintain peripheral tolerance. Thus, TGF-beta may promote allograft acceptance.
      However, TGF-beta is also the central pathogenic cytokine in fibrotic disease and
      likely promotes pneumonitis. Although TGF-beta can enhance leukocyte recruitment
      and IgA production, it inhibits both innate and adaptive immune cell function and
      antiviral host defense posthematopoietic stem-cell transplantation. This review
      will focus on the current understanding of TGF-beta biology and the numerous ways
      it can impact outcomes posttransplant.

PMID- 20671594
TI  - Brain death and Toll-like receptors in lung transplantation.

PMID- 20671595
TI  - Early renal failure after domino liver transplantation using organs from donors
      with primary hyperoxaluria type 1.
AB  - BACKGROUND: Organ shortage is responsible for high mortality rates of patients
      awaiting liver transplantation (LT). Domino transplantation has had reported
      success in patients with metabolic disorders. Primary hyperoxaluria type 1 (PH1)
      is a rare metabolic disorder. There are a few case reports that suggest that PH1
      livers originating from donors that have undergone combined liver-kidney
      transplantation can be successfully used for domino transplantation. METHODS: In
      the last decade, five patients received a domino liver transplant from patients
      with PH1 in the EUROTRANSPLANT region. In this study, we report the clinical
      course and outcome of these five patients who were received a domino graft
      transplant. RESULTS: All patients, with the exception of one, suffered from
      multifocal hepatocellular carcinoma and underwent domino LT from patients
      undergoing combined liver-kidney transplantation for PH1. Within the first 4
      weeks, all the domino recipients developed dialysis-dependent kidney failure
      despite good liver function. Four of the five patients died. The only survivor
      underwent retransplantation due to hepatic artery thrombosis. Twenty months after
      transplantation, this patient is doing well and has had no recurrence of
      hepatocellular carcinoma. CONCLUSION: Domino LT using donors with PH1 results in
      early renal failure and cannot be recommended for transplantation unless
      preventive strategies have been identified.

PMID- 20671596
TI  - Contribution of Toll-like receptor activation to lung damage after donor brain
      death.
AB  - INTRODUCTION: Donor brain death is the first injurious event that can produce
      inflammatory dysfunction after pulmonary transplantation. This study was designed
      to determine whether stimulation of the toll-like receptor (TLR) system
      contributes to the changes produced by brain death. MATERIALS AND METHODS: Rats
      were repeatedly treated with specific agonists for TLR4 or TLR2/6 to desensitize
      these receptors. Brain death was then induced by inflation of a balloon catheter
      within the extradural space. Mean arterial pressure changes and inflammatory
      markers were measured serially by protein and mRNA analysis. RESULTS: Both
      desensitizing pretreatments prevented the neurogenic hypotension (P<0.001) and
      metabolic acidosis (P<0.001) observed in control animals after brain death. These
      treatments also reduced the levels of tumor necrosis factor-alpha and CXCL1 in
      serum and bronchoalveolar lavage fluid, although desensitization of TLR4 produced
      a greater inhibition than desensitization of TLR2. Desensitization of TLR4 also
      reduced (P<0.05) expression of the adhesive integrin CD11b on blood neutrophils
      after brain death. Examination of mRNA levels in lung tissue 5 hr after brain
      death showed that desensitization of TLR4 limited the expression of interferon
      (IFN)-gamma, IFNbeta, and CXCL10, whereas desensitization of TLR2/6 reduced only
      the expression of IFNgamma. CONCLUSION: These results indicate that activation of
      TLR signaling pathways can contribute to the lung damage produced by brain death;
      this may increase subsequent graft injury after transplantation.

PMID- 20671597
TI  - Non-human primate regulatory T cells: current biology and implications for
      transplantation.
AB  - Regulatory T cells (Treg) offer potential for improving long-term outcomes in
      cell and organ transplantation. The non-human primate model is a valuable
      resource for addressing issues concerning the transfer of Treg therapy to the
      clinic. Herein, we discuss the properties of non-human primate Treg and prospects
      for their evaluation in allotransplantation and xenotransplantation.

PMID- 20671598
TI  - An integrative approach for the transplantation of high-risk sensitized patients.
AB  - BACKGROUND: Sensitized patients have a lower chance of receiving a crossmatch
      negative kidney and, if transplanted, are at risk of antibody-mediated allograft
      rejection. METHODS: For safe and timely transplantation of sensitized patients at
      our center, we developed an integrative algorithm that includes identification of
      high-risk patients, good human leukocyte antigen match, inclusion in the
      Eurotransplant Acceptable Mismatch Program when applicable, apheresis, anti-CD20
      therapy, posttransplant antibody monitoring, and protocol biopsies. Thirty-four
      high-risk recipients of a deceased donor kidney (DDK: n=28) or living donor
      kidney (LDK: n=6) were transplanted using this algorithm. RESULTS: One-year graft
      survival, death-censored graft survival, and patient survival rates in DDK
      recipients were 92.4%, 96.4%, and 95.8%, respectively. No graft loss or patient
      death was observed in the six LDK patients. Median serum creatinine at 1 year in
      DDK and LDK recipients was 1.2 and 1.4 mg/dL, respectively. Eleven DDK and three
      LDK patients experienced at least one biopsy-proven acute rejection episode,
      mostly showing borderline changes. Antibody-mediated rejection without graft loss
      was diagnosed in two DDK and one LDK patients. Delayed graft function was
      observed in 13 DDK and 1 LDK patients. Infectious complications were infrequent.
      CONCLUSIONS: We describe an algorithm for the categorization and treatment of
      presensitized high-risk patients. This protocol provides effective prevention of
      antibody-mediated rejection and is associated with a low rate of side effects and
      good graft outcome.

PMID- 20671603
TI  - MALDI imaging mass spectrometry in ovarian cancer for tracking, identifying, and
      validating biomarkers.
AB  - BACKGROUND: Among biomarkers, cancer-antigen 125 (CA-125) is the most studied. We
      propose an analytical tool to track ovarian carcinoma biomarkers, that is, the
      MALDI mass spectrometry imaging. MATERIAL/METHODS: Ovarian carcinomas and benign
      ovaries were directly analyzed by MALDI-TOF-MS. After automatic profiling and
      mass spectrometry imaging analyses, hierarchical clustering based on principal
      component analysis in nonsupervised mode was carried out. On the same samples,
      preparations were performed to investigate peptides, then proteins, followed by
      high mass proteins, in an automatic profiling to specific signatures for
      diagnosis. Using tissue bottom-up strategy on tissue digestion, and mass
      spectrometry imaging after by shotgun sequencing by nalano-LC-IT-MS in MS/MS mode
      from washing samples from on tissue digested peptides, several biomarkers were
      found. RESULTS: A list of specific biomarkers from the ovarian carcinoma regions
      was obtained and classified as proteins associated with cell proliferation,
      involved in immune response modulation, signaling to the cytoskeleton, and tumor
      progression. These specific biomarkers were then validated by immunocytochemistry
      using Tag-mass technology, cell biology, Western blot, and by PCR (using SKOV-3
      ovarian epithelial cancer cells). A link between the immune regulation (innate
      immunity, tolerance) and virus cause is also discussed. CONCLUSIONS: From the
      biomarkers identified, proteins involved in immune response modulation and cell
      proliferation have been pointed out in this study. Two new markers have been
      identified using such a strategy, that is, fragment C-terminal of the PSME1 (Reg
      Alpha) and mucin-9.

PMID- 20671604
TI  - A newly-designed positioning system for simultaneous indocyanine green and
      fluorescein anterior segment angiography of the albino rabbit.
AB  - BACKGROUND: Simultaneous recording of vertical iris indocyanine green angiography
      (ICGA) and iris fluorescein sodium angiography (IFA) in albino rabbits.
      MATERIAL/METHODS: An easily adjusted control system was designed to position the
      CSLO scanning lens perpendicular to the surface of the iris. Twelve albino
      rabbits were randomly divided into 2 groups. Using 5 mg fluorescein sodium and 5
      mg indocyanine green, iris angiograms (IA) of 6 albino rabbits were performed
      with application of the positioning system in Group A, and no positioning system
      in Group B. The time spending on vertical eye position and the effects of
      simultaneous IA were observed. RESULTS: With the use of the positioning system,
      the irises of rabbits quickly achieved the vertical site, averaging 37.50+/-8.17
      s in Group A, and 408.33+/-58.79 s in Group B. The difference was statistically
      significant, and the time saved averaged 370.83 s. Compared with the other
      methods of single-dye angiography, simultaneous digital angiography provided 2
      kinds of full, dynamic videos of iris vessels in all albino rabbits. The
      emergence time of IFA and ICGA was 5-9 s, with an average time for ICGA of 6.4 s,
      and for IFA of 6.5 s. Except for leakage, the simultaneous ICGA and IFA
      appearance of this vascular pattern was the same as the single IFA described
      previously. CONCLUSIONS: Simultaneous vertical IA with indocyanine green and
      fluorescein sodium is a potentially powerful technique that allows high-quality
      fluorescence imaging of the albino rabbit iris.

PMID- 20671605
TI  - Protective action of hepatocyte growth factor on transforming growth factor beta
      1-induced alpha-smooth muscle actin and extracellular matrix in cultured human
      peritoneal fibroblasts.
AB  - BACKGROUND: Peritoneal adhesion is the leading cause of severe mechanical bowel
      obstruction, female infertility, pelvic pain, and difficult surgical procedures.
      TGF-beta1 plays an important role in matrix production associated with
      postoperative peritoneal adhesion development. Recent investigators have shown
      that HGF works on several organs and has been given widespread attention because
      it has proved to have strong antifibrotic activity. The aim of this study was to
      determine the impact of HGF on markers of adhesion formation induced by TGF-beta1
      in human peritoneal fibroblasts. MATERIAL/METHODS: Fibroblasts were collected
      from normal peritoneum and were cultured with 5 ng/ml of TGF-beta1 along with
      increasing doses of HGF (10-40 ng/ml). Expression of alpha-SMA was assessed by
      Western blot. The productions of collagen I and fibronectin in supernatants
      culture were examined by enzyme-linked immunosorbent assay (ELISA). RESULTS: TGF
      beta1 significantly stimulated alpha-SMA, collagen I and fibronectin production
      in peritoneal fibroblasts. Remarkably, the addition of HGF reduced production of
      all components induced by TGF-beta1 in a dose-dependent manner. CONCLUSIONS: This
      study suggests that HGF may be a novel, highly efficacious agent in the
      minimization of intra-abdominal adhesion. Although further studies are needed to
      assess the mechanisms of HGF in neutralizing the effect of TGF-beta1, these
      findings also provide a cellular and molecular basis for the action of HGF as an
      anti-adhesion agent.

PMID- 20671606
TI  - Influence of lisinopril on cardiac remodeling induced by tobacco smoke exposure.
AB  - BACKGROUND: To investigate the effect of lisinopril on cardiac remodeling induced
      by smoking. MATERIAL/METHODS: Rats were allocated into 3 groups: group CON (n=8):
      control; group CSE (n=8): cigarette smoke exposure; group CSE-LIS (n=8): exposed
      to tobacco smoke and treated with lisinopril. RESULTS: After 2 months, the tail
      systolic pressure was lower in CSE-LIS (CON=116 +/-27 mm Hg, CSE=126+/-16, CSE
      LIS=89+/-12; P<.001). CSE animals showed higher left ventricular systolic
      diameter (CON=8.25+/-2.16 mm/kg, CSE=11.5+/-1.3, CSE-LIS=9.27+/-2.00; P=.009) and
      myocyte cross-sectional area (CON=245+/-8 microm2, CSE=260+/-17, CSE-LIS=238+/
      12; P=.01) than CON and CSE-LIS. The ejection fraction (CON =0.91+/-0.02,
      CSE=0.86+/-0.02, CSE-LIS=0.92+/-0.03; P=.002) and fractional shortening
      (CON=55.7+/-4.41%, CSE=48.7+/-3.43, CSE-LI=58.2+/-7.63; P=.006) were lower in CSE
      group than CON and CSE-LIS. CSE and CSE-LIS animals showed higher collagen
      amounts (CON=3.49+/-0.95%, CSE= 5.01+/-1.58, CSE-LIS=5.27+/-0.62; P=.009) than
      CON. CON group showed a higher connexin 43 amount in the intercalated disc
      (CON=3.70+/-0.38, CSE=2.13+/-0.53; CSE-LIS=2.17+/-0.73; P=.004) than CSE and CSE
      LIS. There were no differences in IFN-gamma or TNF-alpha cardiac levels among the
      groups. CONCLUSIONS: Lisinopril attenuated both morphologic and functional
      abnormalities induced by exposure to tobacco smoke. In addition, this effect was
      associated with diminished blood pressure, but not alterations in connexin 43
      distribution, cytokine production or collagen amount.

PMID- 20671607
TI  - Long-term adaptation to high doses of morphine causes desensitization of mu-OR-
      and delta-OR-stimulated G-protein response in forebrain cortex but does not
      decrease the amount of G-protein alpha subunits.
AB  - BACKGROUND: The functional activity of trimeric guanine-nucleotide-binding
      proteins (G-proteins) represents an essential step in linking and regulation of
      the opioid receptor (mu-, delta- and kappa-OR)-initiated signaling pathways.
      Theoretical basis and/or molecular mechanism(s) of opioid tolerance and addiction
      proceeding in the central nervous system were not studied in the forebrain cortex
      of mammals with respect to quantitative analysis of opioid-stimulated trimeric G
      protein activity. MATERIAL/METHODS: G-protein activity was measured in PercollR
      purified plasma membranes (PM) isolated from the frontal brain cortex of control
      and morphine-treated rats by both high-affinity [32P]GTPase and [35S]GTPgammaS
      binding assays. Exposition to morphine was performed by intra-muscular
      application of this drug. Control animals were injected with sterile PBS.
      RESULTS: Both mu-OR (DAMGO)- and delta-OR (DADLE)-responses were clearly
      desensitized in PM isolated from morphine-treated rats; kappa-OR (U-69593)- and
      baclofen (GABAB-R)-stimulated [35S]GTPgammaS binding was unchanged, indicating
      the specificity of the morphine effect. Under such conditions, the amount of G
      protein alpha subunits was unchanged. The order of efficacy DADLE>DAMGO>U-69593
      was the same in control and morphine-treated PM. Behavioral tests indicated that
      morphine-treated animals were fully drug-dependent and developed tolerance to
      subsequent drug addition. CONCLUSIONS: Prolonged exposure of rats to high doses
      of morphine results in decrease of the over-all output of OR-stimulated G-protein
      activity in the forebrain cortex but does not decrease the amount of these
      regulatory proteins. These data support the view that the mechanism of the long
      term adaptation to high doses of morphine is primarily based on desensitization
      of OR-response preferentially oriented to mu-OR and delta-OR.

PMID- 20671608
TI  - Detection of slime and methicillin resistance genes in Staphylococci isolated
      from nasal samples of patients with orthopaedic implants.
AB  - BACKGROUND: The purposes of the present study were (1) to determine the
      prevalence of mecA and femA genes, (2) to investigate the presence of icaA and
      icaD genes responsible for slime synthesis, and (3) to search in vitro slime
      synthesis by staphylococcal strains isolated from the nares of patients with
      orthopaedic implants using the Congo red agar (CRA) plate test. MATERIAL/METHODS:
      Staphylococci strains were defined by multiplex polymerase chain reaction (PCR)
      technique to determine intercellular adhesion genes icaA and icaD. Slime
      production capability was searched by the CRA plate test, phenotypically. Also,
      the presence of mecA and femA genes was determined by PCR in all strains.
      RESULTS: The presence of icaA and icaD was detected in 101 isolates of 134
      (75.4%) strains. This ratio was 74.8% (89 of 119) among the Staphylococcus
      epidermidis and 80% (12 of 15) among the Staphylococcus aureus isolates. A total
      of 63.4% of all the strains were found to be icaA and icaD positive as well as
      slime-forming on the CRA plate test. The percentage of icaA- and icaD-negative
      strains was 36.6%, and all of them were negative on the CRA plate test. Although
      femA presence was detected in all 15 (11.2%) S. aureus isolates, a total of 5
      (3.7%) isolates carried the mecA gene. CONCLUSIONS: The frequency of icaA and
      icaD genes was determined to be of high prevalence among staphylococcal isolates.
      The staphylococcal strains that were found in the nasal flora of patients with
      orthopaedic implants may be important potential sources of infection for these
      patients.

PMID- 20671609
TI  - Hypertrophied myocardium is more dependent on extracellular calcium than the
      normal cardiac muscle.
AB  - BACKGROUND: The aim of this study was to analyze stable hypertrophied myocardial
      function and its response to inotropic maneuvers in rats submitted to
      renovascular hypertension for a 10-week period (RHT group, n=10).
      MATERIAL/METHODS: Myocardial performance was studied in isolated left ventricle
      papillary muscles in isometric contraction under the following conditions: at
      postrest contraction of 30 seconds (PRC), at extracellular calcium (ECa2+)
      chloride concentration of 1.25 and 5.20 mM, and after beta-adrenergic stimulation
      with 10-6 M isoproterenol (ISOP). RESULTS: The results were compared with
      normotensive Wistar controls rats (C group, n=10). In basal condition, resting
      tension, and contraction time (TPT) were greater, while relaxation time (RT50)
      tended to be longer in RHT than C group. PRC and ISOP promoted a similar change
      in muscle function response intensity (delta) in both groups. ECa2+ shift did not
      change TPT in the C group and decreased TPT in the RHT animals; delta was
      different between these groups. RT50 increased in C and decreased in RHT, both
      without statistical significance; however, delta was different. CONCLUSIONS:
      These results suggest that hypertrophied myocardial dysfunction may be attributed
      to changes in intracellular calcium cycling.

PMID- 20671610
TI  - Protective effects of aqueous fruit extract from Sea Buckthorn (Hippophae
      rhamnoides L. Spp. Turkestanica) on haloperidol-induced orofacial dyskinesia and
      neuronal alterations in the striatum.
AB  - BACKGROUND: Long-term treatment of haloperidol, a neuroleptic, induces
      neurodegeneration specifically in the striatum (caudate and putamen), which plays
      an important role in the development of orofacial dyskinesia, a putative model of
      tardive dyskinesia (TD). This study investigated the protective effects of a
      concomitant treatment of aqueous fruit extract of Sea buckthorn (Hippophae
      rhamnoides L. spp. Turkestanica) (SBT-FE) (40 mg/kg, orally) plus haloperidol
      (3.0 mg/kg, ip) administration on an animal model of TD and on striatal neuronal
      alterations. MATERIAL/METHODS: Rats received daily haloperidol (3.0 mg/kg ip) and
      saline injections for 15 days. Seven-day posttreatment, aqueous SBT-FE (40 mg/kg)
      was administered daily via a feeding tube. Hypolocomotive effects (home cage
      activity, exploratory activity, catalepsy, and vacuous chewing movements) were
      monitored consecutively in each group. On the last day of the experiments,
      changes in extracellular levels of striatal dopamine (DA), dihydroxyphenyl acetic
      acid (DOPAC) and homovanillic acid (HVA) were determined by HPLC-EC. RESULTS:
      Aqueous SBT-FE attenuated haloperidol-induced VCMs after second week of treatment
      and locomotor activity was greater in rats treated with SBT-FE compared with the
      controls. The results indicate that DA and HVA levels in the striatum were
      significantly (P <.01) altered in rats given SBT-FE before injections of
      haloperidol. CONCLUSIONS: Hippophae rhamnoides fruit extract has a protective
      role against haloperidol-induced orofacial dyskinesia. Consequently, use of
      Hippophae rhamnoides as a possible therapeutic agent for the treatment of tardive
      dyskinesia should be considered.

PMID- 20671611
TI  - Gene expression levels of CSNK1A1 and AAC-11, but not NME1, in tumor tissues as
      prognostic factors in NSCLC patients.
AB  - BACKGROUND: To analyze the prognostic significance of the genes casein kinase 2
      alpha subunit (CSNK2A1), anti-apoptosis clone-11 (AAC-11), and tumor metastasis
      suppressor NME1 in completely resected non-small cell lung cancer (NSCLC)
      patients. MATERIAL/METHODS: Total RNA was extracted from 145 cases of completely
      resected, formalin-fixed, paraffin-embedded NSCLC tissues. mRNA expression levels
      of CSNK2A1, AAC-11, and NME1 were detected by real-time reverse-transcriptase
      polymerase chain reaction. Univariate and multivariate survival analyses were
      used to identify factors related to prognosis. RESULTS: A correlation between
      CSNK2A1 and AAC-11 mRNA expression levels (rs=0.366, p=0.000) was found.
      Univariate analysis showed that high expression of CSNK2A1 and AAC-11 was
      predictive of poor prognosis in NSCLC patients (p=0.029 and 0.044, respectively),
      especially when expression levels of both genes were concomitantly high
      (p=0.007). Multivariate Cox regression analysis showed that high expression of
      CSNK2A1, or concomitantly high expression of CSNK2A1 and AAC-11, are independent
      prognostic factors of poor survival in NSCLC patients. However, NME1 mRNA
      expression level did not significantly influence survival in NSCLC patients.
      CONCLUSIONS: This retrospective study indicates that CSNK2A1 and AAC-11,
      especially in combination, are useful prognosis markers in NSCLC patients after
      complete resection, independent of lymph node metastasis status.

PMID- 20671612
TI  - Preoperative prevalence of methicillin-resistant Staphylococcus aureus (MRSA)
      colonization in patients undergoing intranasal surgery.
AB  - BACKGROUND: The goal of this study was to determine the rates of carriage of
      methicillin-resistant Staphylococcus aureus among patients undergoing intranasal
      surgery. MATERIAL/METHODS: One hundred and sixty five patients undergoing
      inpatient and outpatient rhinologic surgery over a six-month period were enrolled
      in the study. Patients completed a short questionnaire prior to surgery. Culture
      swabs of the anterior nares and nasal vestibule were sent to the microbiology lab
      for evaluation for methicillin-resistant Staphylococcus aureus. Cultures were
      grown on a MRSA-specific agar plate and were considered final after 48 hours of
      incubation. The primary endpoint was a positive MRSA culture. RESULTS: Of the one
      hundred fifty seven patients with nasal cultures taken, two had positive cultures
      for methicillin-resistant Staphylococcus aureus. Of those with positive cultures,
      both had a history of prior infection with methicillin-resistant Staphylococcus
      aureus. CONCLUSIONS: While antibiotic usage among the study group is far higher
      than the national average, the rates of nasal carriage of methicillin-resistant
      Staphylococcus aureus mirrors that described in other studies for the general
      population. The authors conclude that methicillin-resistant Staphylococcus aureus
      does not represent a significant source of infection among those undergoing
      intranasal surgery.

PMID- 20671613
TI  - Meta-analysis of association between optineurin gene and primary open-angle
      glaucoma.
AB  - BACKGROUND: Glaucoma is the leading cause of irreversible blindness in the world.
      Recent evidence indicates genetic susceptibility plays a role in primary open
      angle glaucoma (POAG). The authors systematically investigated the association
      between optineurin (OPTN) gene polymorphisms and POAG. MATERIAL/METHODS: A meta
      analysis of 25 published genetic association case-control studies, which examined
      the relation between POAG and the M98K, T34T, and R545Q polymorphisms of the OPTN
      gene, was carried out. RESULTS: For the T34T polymorphism, overall, the
      heterogeneity between studies was significant (P=0.0009), and the allele A was
      not associated with the risk of POAG relative to allele G (odds ratio: 1.14 [95%
      CI, 0.93 to 1.40]). In Asians and adults, the dominant model for allele A
      produced significant results (odds ratios: 1.50 [1.23 to 1.82] and 1.45 [1.10 to
      1.91], respectively). Asian subjects also showed significance under the allele
      contrast model; however, the recessive model produced no significant results.
      Regarding the M98K and R545Q polymorphisms, the overall analysis did not detect a
      statistically significant association (odds ratios for the allele contrast
      models: 1.16 [0.96 to 1.40] and 1.14 [0.93 to 1.40], respectively). CONCLUSIONS:
      There is evidence of a modest positive association only between T34T polymorphism
      and POAG in Asians and adults. The M98K and R545Q polymorphisms have no
      association with POAG susceptibility. However, this meta-analysis exploring
      combinations of the polymorphisms may help us better understand the genetics of
      POAG.

PMID- 20671614
TI  - Attenuated lactate response to ischemic exercise in migraine.
AB  - BACKGROUND: Although the pathogenesis of migraine still remains unclear, certain
      metabolic studies done on patients with migraine indicate possible deficits in
      mitochondrial activity. Previously, the forearm ischemic exercise test (FIT) has
      been used as a screening tool to evaluate mitochondrial dysfunction in metabolic
      myopathies. MATERIAL/METHODS: We studied the response of migraine patients to
      exercise using the modified FIT and compared this to the responses in a healthy
      group. After baseline venous blood samples were drawn, a sphygmomanometer cuff
      placed around the upper arm was inflated to 30 mmHg above systolic blood pressure
      and the subject performed a maximal isometric contraction of the forearm flexors
      using a hand-grip dynamometer with a 9-contraction: 1-relaxation duty cycle for a
      total time of 60 seconds. RESULTS: In migraine patients, attenuated lactate
      response after the FIT in the 1st, 3rd and 5th minutes were significantly
      different when compared to the control group. CONCLUSIONS: Our results show that
      there may be defects in the anaerobic or proximal glycolytic pathways in migraine
      patients, evident in stressful situations. We also conclude that the FIT may be
      useful for research on migraine pathophysiology.

PMID- 20671615
TI  - Predictive significance of TCI-R for antidepressant treatment.
AB  - BACKGROUND: The aim of this study was to investigate the significance of the
      Temperament and Character Inventory-Revised (TCI-R) dimensions of personality for
      prediction of treatment outcome in depressed outpatients during 6 months of
      antidepressant treatment. MATERIAL/METHODS: Thirty outpatients were treated for
      mild or moderate depressive episode, current mild or moderate episode of
      recurrent depressive disorder or mixed anxiety and depressive disorder (ICD-10).
      The intensity of depression was assessed by the Montgomery-Asberg Depression
      Rating Scale (MADRS) at the beginning of treatment and then after the 1st, 3rd
      and 6th months of treatment. The personality dimensions were assessed by the TCI
      R at the same time points as the MADRS. Differences in TCI-R dimensions between
      treatment responders (> or =50% decrease in MADRS score after 6 months of
      treatment) and nonresponders (<50% decrease in MADRS score) were compared by
      repeated measures analysis of variance (ANOVA). Predictive value for the
      treatment outcome was assessed by Spearman's correlation coefficient. RESULTS:
      The predictive significance for treatment outcome (Spearman's correlation
      coefficient) was identified for reward dependence (RD) (R=-0.44) and harm
      avoidance (HA) (R=0.46) dimensions. Treatment responders and nonresponders
      significantly differed (ANOVA) in HA (p<0.05), showing a decrease in total mean
      HA score only in responders during treatment. CONCLUSIONS: Our findings showed
      predictive significance of the TCI-R dimensions HA and RD for long-term
      antidepressant treatment outcome.

PMID- 20671616
TI  - Successful treatment of Immune Thrombocytopenic Purpura (ITP) with the
      thrombopoietin-mimetic romiplostim.
AB  - BACKGROUND: Romiplostim is a second-generation thrombopoietic receptor agonist
      that exerts its therapeutic effect by stimulating megakaryopoiesis. CASE REPORT:
      We report a patient with immune thrombocytopenic purpura refractory to other
      therapies including splenectomy, which was successfully managed with romiplostim.
      More specifically, the patient's platelet count showed a 3-fold increase within 7
      days following the first dose of romiplostim (from 33 x 10(9)/l to 96 x 10(9)/l).
      CONCLUSIONS: Romiplostin is a new trombopoietin peptide mimetic drug, which seems
      to be very effective for the management of refractory chronic ITP in adults.

PMID- 20671617
TI  - Eosinophilic ulcer of the oral mucosa: report of a child with CD30-negative cells
      in an infiltration on the lower lip.
AB  - BACKGROUND: Eosinophilic ulcer of the oral mucosa (EUOM), also known as traumatic
      eosinophilic granuloma or Rida-Fede disease, is an uncommon, benign and self
      limited lesion of the oral mucous membrane. The tongue is the most common
      location of EUOM, accounting for up to 60% of the cases, with the lateral and
      dorsal surfaces being principally affected. EUOM clinically manifests as a
      painful, nodular inflammatory infiltration, usually with ulceration.
      Characteristic histological findings consist of dense subepithelial, mixed
      inflammatory infiltration with numerous eosinophils. The etiology of the disease
      is unknown. CASE REPORT: We present a case of a 9-year-old boy, in whom a painful
      ulceration, nonresponding to typical antiviral and antibacterial treatment,
      occurred on the lower lip. The histological study revealed intact epithelium
      without the unequivocal signs of cellular atypia and a dense infiltrate in the
      stroma mainly composed of eosinophils and histiocytes with CD30-negative cells.
      The histological diagnosis of EUOM was given. A rapid resolution of the lesion
      was observed following biopsy. CONCLUSIONS: EUOM, a relatively rare and benign
      disease, infrequently presenting as a lesion on lips, may cause diagnostic
      difficulties to dermatologists as well as to dental surgeons and ENT specialists.
      Biopsy is recommended to rule out malignant etiology and avoid overtreatment.

PMID- 20671618
TI  - Delta6 desaturase as the target of the beneficial actions of magnesium.

PMID- 20671619
TI  - Timing of dexamethasone administration.

PMID- 20671620
TI  - A prospective study using color flow duplex ultrasonography for abdominal
      perforator mapping in microvascular breast reconstruction.
AB  - BACKGROUND: Abdominally based perforator free flaps are commonly used in
      reconstructive breast surgery. Pre-operative assessment using a variety of
      imaging techniques has become increasingly popular to assess the anatomy of the
      abdominal perforators. We hypothesize that color flow duplex ultrasonography is a
      reliable method for mapping the abdominal perforator anatomy and avoids the
      complications associated with other methods. MATERIAL/METHODS: A prospective
      study of 40 consecutive patients was performed. Pre-operative color flow duplex
      ultrasound evaluation was compared to intra-operative findings of the dominant
      epigastric perforator selected at the time of flap harvest. RESULTS: Forty
      consecutive patients were evaluated prospectively. Forty six flaps were harvested
      from these patients (6 bilateral cases). A single perforator which was identified
      by both pre-operatively and at the time of intra-operative flap harvest as the
      dominant perforator was identified in 36 of 46 flaps (78.3%). The intra-operative
      perforator chosen at the time of flap harvest was identified as one of the pre
      operative perforators marked by duplex ultrasonography in 45 or 46 patients
      (97.8%). CONCLUSIONS: Pre-operative duplex ultrasonography is a safe and reliable
      tool for assessing the abdominal epigastric perforators used in autologous
      microvascular breast reconstruction. Advantages of this technique are: it is non
      invasive, it does not require contrast agent application, no radiation, and it is
      inexpensive when compared to other imaging modalities.

PMID- 20671622
TI  - Risk factors and outcomes of intensive care unit-acquired infections in a
      Tunisian ICU.
AB  - BACKGROUND: ICU-acquired infections constitute an important world-wide health
      problem. Our aim was to determine the incidence, predictive factors and impact of
      ICU-AIs in ICU patients in Tunisia. MATERIAL/METHODS: We conducted a prospective
      observational cohort study over a 3 month period in the medical surgical
      intensive care unit of Habib Bourguiba University Hospital (Sfax-Tunisia).
      RESULTS: During the study period 261 patients were surveyed; 44 of them (16.9%)
      developed 55 episodes of ICU-AI (34.7 ICU-AI/1000 days of hospitalization). The
      most frequently identified infections were ventilator-associated pneumoniae
      (58.2%), and primary bloodstream infection (18.2%). The most frequently isolated
      organisms were multidrug-resistant P. aeruginosa (44.7%), and A. baumannii
      (21.3%). The initial antibiotic prescription for ICU-AI was inadequate in 9 cases
      (16.4% of episodes of ICU-AI). At ICU discharge, overall mortality was 29.9%.
      Independent risk factors for acquiring infection in ICU were the use of central
      venous catheter (p=0.014) and antibiotic prescription on admission for more than
      24 hours (p=0.025), those of mortality in ICU were SAPS II of more than 35 points
      (p<0.001) and ICU-AI (p=0.002), and those of mortality at 28 days after an
      episode of ICU-AI were septic shock (p=0.004) and inadequate initial
      antimicrobial treatment (p=0.011). CONCLUSIONS: We conclude that the occurrence
      of ICU-AI is significantly related to increased mortality, and that focusing
      interventions on better use of antibiotics would have a benefit in terms of
      prevention and consequences of ICU-AI.

PMID- 20671624
TI  - Renal consequences of obesity.
AB  - The worldwide prevalence of obesity and its associated metabolic and
      cardiovascular disorders has risen dramatically within the past 2 decades. Our
      objective is to review the mechanisms that link obesity with altered kidney
      function. Current evidence suggests that excess weight gain may be responsible
      for 65-75% of the risk for arterial hypertension. Impaired renal pressure
      natriuresis, initially due to increased renal tubular sodium reabsorption, is a
      key factor linking obesity with hypertension. Obesity increases renal sodium
      reabsorption by activating the renin-angiotensin and sympathetic nervous systems,
      and by altering intrarenal physical forces. Adipose tissue functions as an
      endocrine organ, secreting hormones/cytokines (e.g., leptin) which may trigger
      sodium retention and hypertension. Additionally, excess visceral adipose tissue
      may physically compress the kidneys, increasing intrarenal pressures and tubular
      reabsorption. Eventually, sustained obesity via hyperinsulinemia, due to
      resistance to insulin, causes hyperfiltration, resulting in structural changes in
      the kidneys--glomerular hyperthrophy and occasionally focal segmental
      glomerulosclerosis. The consequences of kidney injury are continuous loss of
      glomerular filtration rate, further increase of arterial pressure and escalation
      of cardiovascular morbidity and mortality. There is a growing awareness of the
      renal consequences of obesity, and considerable progress is being made in
      understanding its pathophysiology. Weight reduction results in lowered
      proteinuria. Aside from low sodium diet and exercises, more widespread use of
      renoprotective therapy (e.g., ACE inhibitors and statins) in treatment of
      hypertension in obese subjects should be advocated. Renal protection should
      result in reducing the cardiovascular complications of obesity.

PMID- 20671623
TI  - Efficacy and safety of intravenous stronger neo-minophagen C and S-adenosyl-L
      methionine in treatment of pregnant woman with chronic hepatitis B: a pilot
      study.
AB  - BACKGROUND: There have been no studies evaluating the efficacy and potential
      risks of stronger neo-minophagen C (SNMC) in pregnant women with chronic
      hepatitis B CHB. MATERIAL/METHODS: A total of 36 pregnant women with CHB, but
      without severe complications, were randomized to intravenously receive SNMC or S
      adenosyl-L-methionine (SAM) daily for 4 weeks or until birth. Normalization of
      serum alanine transaminase (ALT) and aspartate transaminase (AST) levels and
      changes in ALT and AST levels from baseline were determined. All neonates were
      regularly examined for up to 1 year. RESULTS: Treatment with SNMC and SAM
      resulted in normalization of ALT levels at 4 weeks in 64.3% and 21.4% of
      patients, respectively (OR=6.60, 95% CI: 1.23-35.44, P=0.0540). SNMC and SAM
      significantly decreased ALT (from 558.28+/-390.24 to 47.07+/-24.94 IU/L, P<0.0001
      and from 525.61+/-483.87 to 117.43+/-85.44 IU/L, P=0.0041, respectively) and AST
      (from 419.72+/-409.49 to 38.14+/-18.87 IU/L, P=0.0016, and from 510.78+/-621.58
      to 79.93+/-63.25 IU/L, P=0.0152, respectively) at 4 weeks relative to baseline
      values. Hypokalemia was observed in 4 SNMC-treated patients and in 2 SAM-treated
      patients and hypernatremia in 3 SNMC-treated and in 3 SAM-treated patients.
      Hypertension was observed in 1 SNMC-treated patient. There was no significant
      difference in the volume of amniotic fluid or meconium between SNMC-treated and
      SAM-treated groups. All the neonates were physically normal at birth and at the 1
      year follow-up examination. CONCLUSIONS: Both SNMC and SAM improve liver
      function, with SNMC appearing more effective, in pregnant women with chronic
      hepatitis B without impact on fetal development.

PMID- 20671625
TI  - Mass-media and the transplantation crisis: the example of Poland.
AB  - Organ transplantation is a treatment method that is very sensitive to public
      opinion. Information regarding misconduct in the recovery and transplant of
      organs very often leads to a definite decrease in the numbers of operations. In
      2007 in Poland, the national media reported numerous controversial
      transplantation incidents. Directly after these occurrences, the number of
      transplantations fell sharply. Public opinion worsened as did the level of trust
      placed in doctors. Social psychology explains the mechanisms responsible for this
      phenomenon through the notion of cognitive schemata. Their permanence is
      explained through selective perception, memory and the effect of persistence.

PMID- 20671626
TI  - Modafinil for narcolepsy: systematic review and meta-analysis.
AB  - BACKGROUND: To assess the effectiveness and safety of modafinil vs. no active
      treatment or other drugs in the treatment of narcolepsy. MATERIAL/METHODS: The
      following electronic databases were searched throughout January 2009: MEDLINE,
      EMBASE and The Cochrane Library. Additional references were obtained from
      reviewed articles. Only randomized controlled trials were included. RESULTS: We
      included 9 trials involving 1,054 patients in the study. Modafinil in comparison
      with placebo brings significant benefit in terms of elimination of excessive
      daytime sleepiness assessed by: ESS scale--weighted mean difference (WMD) -2.73
      points (95%CI -3.39, -2.08), MSLT test--WMD 1.11 minutes (95%CI 0.55, 1.66) and
      MWT test--WMD 2.82 minutes (95%CI 2.40, 3.24), as well as the number and duration
      of somnolence, sleep attacks and naps per day, but was not different from placebo
      in the number of attacks of cataplexy per day. Modafinil in comparison with
      placebo improved quality of life of narcoleptic patients according to SF-36
      questionnaire, but was associated with more common nausea. It had similar effect
      on excessive daytime sleepiness as sodium oxybate and was associated with less
      common nausea. CONCLUSIONS: In narcoleptic patients, modafinil in comparison with
      placebo is effective in the treatment of excessive daytime sleepiness, but not
      cataplexy.

PMID- 20671627
TI  - Ischemic post-conditioning: a feasible preventive method for cerebral
      hyperperfusion syndrome secondary to revascularization.
AB  - Cerebral hyperperfusion syndrome is a serious complication of revascularization
      after carotid endarterectomy, extracranial-intracranial bypass surgery, or stent
      placement. The mechanisms underlying cerebral hyper-perfusion syndrome are mainly
      ascribed to the dysfunction of cerebral auto-regulation to blood flow and injury
      of the endothelia in blood vessels. Although blood pressure control is often used
      to prevent cerebral hyper-perfusion after revascularization, cases of cerebral
      hyperperfusion are still reported in the literature. Current animal studies have
      shown that ischemic post-conditioning has protective effects on brain tissue, and
      further studies also showed that it had positive effects on human brachial artery
      and heart. Therefore, we propose the hypothesis that ischemic post-conditioning
      could be used to prevent cerebral hyperperfusion syndrome following
      revascularization. Although the mechanism of ischemic post-conditioning and its
      clinical application should be further investigated, it has shown its potential
      effectiveness as a feasible method for prevention of cerebral hyperperfusion
      syndrome.

PMID- 20671628
TI  - Effect of Khat (Qat) consumption on pain during and after local anesthesia for
      patients undergoing cataract surgery.
AB  - BACKGROUND: The leaves of the Khat (Qat) plant (Catha edulis), which contain
      amphetamine-like compounds, are widely chewed in Yemen and East Africa for their
      pleasurable stimulant properties and for their psychostimulative effects. Khat
      consumption has a number of unwanted side-effects. This study investigates
      effects of Khat consumption on the quality of local anesthesia with peribulbar
      injection and patient perception of pain after administration of local anesthesia
      for routine cataract extraction. MATERIAL/METHODS: This single-center,
      prospective trial included 323 consecutive patients undergoing routine cataract
      extraction for senile cataract. Cataract surgery was performed within 10 minutes
      of the administration of local anesthesia. The patients were divided into 2
      groups: Group A for those who are consuming Khat on a regular basis and Group B
      for those who had not consumed Khat within the last 3 months. To assess pain
      experience during injection, intraoperatively, and postoperatively, each patient
      was asked to use a 10-point pain score chart. RESULTS: The study included 164
      males and 159 females. There were 121 patients (37.5%) in Group A and 202
      patients (62.5%) in group B. All patients had peribulbar local anesthesia by 2
      site injections. Group A had significantly greater pain scores during injection
      (p=0.000821) and intraoperatively (p=0.000001), but there was no difference in
      pain score postoperatively. CONCLUSIONS: Khat consumption decreases pain
      threshold and affects patients' comfort during local anesthesia and during
      surgery in routine cataract surgery. Patients consuming Khat need more care
      during local anesthesia to make the surgery comfortable.

PMID- 20671629
TI  - Use of the AorfixTM stent graft in patients with tortuous iliac anatomy.
AB  - AIM: Iliac limb occlusion following endovascular repair (EVAR) may result in limb
      threatening acute ischemia. The incidence is reported at up to 10% and is known
      to be influenced by iliac angulation and kinking of the stent graft. The aim of
      this study was to evaluate the performance of the AorfixTM graft in tortuous
      iliac anatomy and examine the impact of the graft on the rate of iliac limb
      thrombosis following EVAR in a single UK centre METHODS: We performed a
      retrospective review of all EVAR performed from May 1998 to May 2010. From
      November 2007, patients with highly angulated iliac anatomy were treated with the
      AorfixTM(Lombard) stent graft, or when a ZenithTM(Cook) main body was chosen, the
      AorfixTM iliac limbs were used with the ZenithTM(Cook) device. We compared the
      rate of iliac limb occlusions before (group 1) and after (group 2) the adoption
      of this policy. RESULTS: Two hundred and sixty seven patients underwent EVAR
      (group 1 n=129; group 2 n=138). In group 1, eight patients had a unilateral iliac
      limb occlusion (6.2%). Six of the patients had >90 degrees iliac angulation, one
      had an unrecognised limb stenosis, and one patient had the stent landed in the
      external iliac. In group 2 there were no limb occlusions. Of the 138 patients, 25
      had iliac angulation of >90 degrees . Of these 25, eighteen were treated with the
      AorfixTM stent graft system because of iliac angulation, and 7 were treated with
      AorfixTM legs and ZenithTM bodies. CONCLUSION: The rate of early iliac limb
      occlusion following EVAR in patients with angulated iliac anatomy can be
      substantially reduced by using the flexible Aorfix stent graft system.

PMID- 20671630
TI  - Ring-stents supported infrarenal aortic endograft fits well in abdominal aortic
      aneurysms with tortuous anatomy.
AB  - AIM: Abdominal aortic aneurysms (AAA) with severe angulation of the neck or of
      the iliac arteries are often unsuitable for endovascular repair with conventional
      endografts. We evaluated the performance of a ring-stent abdominal endograft
      (AnacondaTM Vascutek, Terumo, Scotland) in a consecutive series of infrarenal
      AAA. METHODS: Preoperative, procedural and follow-up data of patients treated
      with AnacondaTM endograft between September 2005 and September 2009 were
      prospectively enrolled. Patients were divided in Group A (proximal neck angle >
      or =60 degrees or iliac arteries angle > or =90 degrees ) and Group B (all
      others). Main endpoints were technical and clinical success (primary and
      assisted) and late outcome in the two groups. Results were compared by Kaplan
      Meier life table analysis with log-rank test (Mantel-Cox). RESULTS: One hundred
      twenty-seven patients, with a mean age of 73.5+/-6.9 years, have been included in
      this series. Mean aneurysm size was 56.7+/-10.4 mm. A severe angulation of the
      proximal aortic neck or/and of the iliac arteries was present in 44 cases (Group
      A), absent in 83 cases (Group B). The mean follow-up was 18.2+/-16.3 months.
      Overall primary technical success was achieved in 100% of the patients. At twenty
      four months survival, primary and assisted clinical success were 94.2%, 88.2% and
      91.3% in Group A and 80.3%, 83.7% and 95.2% in Group B respectively. No
      significant differences were found between the two groups. The only factor
      significantly associated with decreased survival was preoperative renal
      insufficiency. Iliac limb patency 24 months after EVAR in severely and non
      severely angulated iliac axis was 96.7% and 98.1% respectively, with no
      significant difference between the groups. Only one proximal type I endoleak was
      detected in a patient with severe angulation of proximal aortic neck. No
      significant correlation between proximal type I endoleak and severe neck
      angulation was found. CONCLUSION: Aneurysms with severe neck or iliac arteries
      angulation can be treated by a ring-stent endograft with results similar to those
      of AAA with more favourable anatomy.

PMID- 20671631
TI  - New results with 100 Excluder cases.
AB  - AIM: The purpose of this study was to report the outcome of EVAR using EXCLUDER
      endoprosthesis (W. L. Gore & Associates, Flagstaff, Ariz.) with low-porosity
      polytetrafluoroethylene (PTFE) in the medium term. We reviewed a 10-year
      experience with this device to document the outcome of 100 consecutive elective
      EVARs with Excluder-Device performed at a single centre. METHODS: From 01.2006 to
      01.2009 all elective abdominal aortic aneurysm (AAA) cases (N=100) with an
      abdominal aortic aneurysm (AAA; mean diameter 5.61 cm; range 4.2-7.3 cm) that
      were treated electively with the EXCLUDER Bifurcated Endoprosthesis were entered
      in an index. Anatomical and clinical evaluations and radiological results have
      been analyzed. Mean aortic neck length was 12.24 mm, mean proximal aortic
      diameter was 24.39 mm. Primary outcome that has been examined, include operative
      mortality, aneurysm rupture, aneurysm-related mortality, open surgical
      conversion, and late survival rates. The incidence of endoleak, migration,
      aneurysm enlargement, and graft patency have also been determined. Finally, the
      need for reinterventions and success of such secondary procedures were evaluated.
      Endoleaks were diagnosed from contrast-enhanced computed tomography, the rate of
      type II endoleaks was analyzed after 1, 3 and 12 months. RESULTS: Mean patient
      age was 74.1 years (range 44-91 years); 91% were male. Mean follow-up was 20
      months; 78 % of the patients had 2 or more major comorbidities, and 32 % were
      categorized as inappropriate for open repair. On an intent-to-treat basis, device
      deployment was successful in 100%. Thirty-day mortality was 0%; freedom from AAA
      rupture was 100%. Type II endoleak appeared directly after the procedure in 24%,
      after 3 months in 15% and after 12 months in 7%. The initial technical success
      defined as endovascular aneurysm exclusion and absence of type I endoleak was
      99%. Proximal type I early endoleak occurred (detected by intraoperative DSA) in
      3 patients, in 2 cases intraoperative proximal aortic cuffs were needed to seal
      proximal type I endoleaks. In one case we performed a proximal bending via a
      retroperitoneal access and sealed the endoprosthesis. Postoperatively, the size
      of the AAA decreased or remained unchanged in 93% after 12 months. Freedom from
      reinterventions was 94% after 2 years. CONCLUSION: EVAR using the EXCLUDER-Device
      is a safe, effective, and durable method to prevent AAA rupture and aneurysm
      related death. Assuming suitable AAA anatomy, these data justify a broad
      application within a wide spectrum of patients.

PMID- 20671632
TI  - Rationale and design of the Endurant Stent Graft Natural Selection Global
      Postmarket Registry (ENGAGE): interim analysis at 30 days of the first 180
      patients enrolled.
AB  - AIM: The Endurant Stent Graft Natural Selection Global Postmarket Registry
      (ENGAGE) is a long-term 1200-patient multicenter prospective study initiated to
      augment the knowledge base (poolable and comparable) about endovascular aortic
      repair (EVAR) in a real-world population implanted with a single latest
      generation stent graft system (Endurant). With enrollment ongoing at 80 high
      volume sites, the registry has limited inclusion/exclusion criteria or procedural
      specification. Technical and clinical data will be reported through 5 years.
      METHODS: An interim analysis was performed on investigator-reported data for the
      first 180 patients enrolled. These patients were asymptomatic elderly males
      (92.1%) with considerable comorbidities. For 47.3% of the patients, the American
      Society of Anesthesiologists risk class was either III or IV. The Endurant stent
      graft was successfully deployed in 99.4% of patients for elective treatment of
      abdominal aortic aneurysm. RESULTS: Through 30 days, the rate of all-cause
      mortality was 1.7% (N=3), with all 3 deaths classified as procedure-related but
      not device-related. The rate of secondary endovascular procedures was 1.1%, and
      the rate of conversion to open repair was 0.6%. At postprocedure and at 30-day
      follow-up, there were no type I or type III endoleaks and no instances of stent
      graft kinking, thrombosis, or occlusion. ENGAGE represents the largest real-world
      registry for any single EVAR stent graft. CONCLUSION: The interim results through
      30 days of the first 180 patients enrolled are promising. Longer-term follow-up
      for more patients will be reported.

PMID- 20671633
TI  - Totally percutaneous aortic aneurysm repair: methods and outcomes using the fully
      integrated IntuiTrak endovascular system.
AB  - AIM: A totally percutaneous approach to endovascular abdominal aortic aneurysm
      repair (PEVAR) has been shown in multiple reports to be feasible, but carries
      attendant risks that appear to increase with increasing sheath size. We report
      our methods and sequential PEVAR case experience using a new delivery system
      having an integrated 19Fr introducer sheath for treatment of patients with aortic
      necks up to 32 mm in diameter. METHODS: A single institution, prospective,
      controlled evaluation was conducted in 57 consecutive patients with abdominal
      aortic aneurysm who underwent PEVAR between December 2008 and April 2010. All
      patients have been followed for at least 30 days. RESULTS: Patients presented at
      a mean age of 74 years with median AAA diameter of 5.4 cm preprocedurally.
      Calcified/tortuous access vessels were identified in 98% of patients. All PEVAR
      procedures with adjunctive "pre-close" use of the Prostar XL closure device were
      performed in a hybrid endovascular suite with patients maintained under conscious
      sedation and local anesthesia. The anatomically-fixed bifurcated stent graft and
      aortic/limb extensions as needed were implanted via the 19 Fr indwelling
      introducer sheath with minimal blood loss (79 mL). Technical success was 98%,
      with one conversion to open repair attributable to very small diameter (4 mm)
      access vessels. Cumulatively, major access-related complications were observed in
      five patients (8.8%) within 30 days. CONCLUSION: PEVAR using the IntuiTrak System
      with 19Fr introducer sheath with vessel closure facilitated by the Prostar XL
      device is feasible, even in patients with challenging access anatomy. Further
      evaluation in a prospective, multicenter, randomized trial is warranted.

PMID- 20671634
TI  - New results with the Zenith graft in the treatment of aortic aneurysms.
AB  - Aneurysmal disease of the arterial vasculature has been reported since ancient
      times. Regarding aneurysms of the aorta, a steady progress has been made ranging
      from making such pathology amenable to surgical treatment to making the procedure
      much less invasive. There have been a number of stent grafts, introduced by
      different companies, used to exclude different segments of the aneurysmal aorta
      and the Zenith devices are one of them. The safety and efficacy of these devices
      to exclude infrarenal and descending thoracic aortic aneurysms has been well
      documented. The early and late complications associated with these procedures and
      the methods used to manage such complications have also been elucidated in
      different publications. In dealing with pararenal and thoracoabdominal aneurysms,
      the need to ensure patency of the visceral vessels while still repairing the
      aorta to healthy tissue must be considered. Strategies involving fenestrations
      and side-arm branches have evolved extending the ability to treat the entire
      aorta with an endovascular approach. Challenges exist including the inherent
      tortuosity and mobility of the aortic arch, close approximation of the supra
      aortic vessels, small or multiple renal vessels, the commonly noted arcuate
      ligament compression of the celiac artery, but great strides have been made and
      virtually all pathologies have been addressed. The desire for smaller delivery
      systems has spurred interest in low-profile devices. This manuscript is intended
      to address the latest developments and clinical results for endovascular grafting
      of the aorta.

PMID- 20671635
TI  - Device-specific outcomes after endovascular abdominal aortic aneurysm repair.
AB  - Over the last decade, endovascular aneurysm repair (EVAR) has been used
      extensively for the elective treatment of infra-renal abdominal aneurysms.
      However, it remains unclear how specific devices perform and how they compare to
      others. We provide an overview of currently used endografts, and discuss the
      current evidence regarding device-specific outcomes. Published literature
      confirms differences in results according to endograft selection. These
      differences were more pronounced with older generations of devices, in comparison
      to newer models. Contemporary results are generally good and one should remember
      that no randomized data exist regarding individual device performance. Moreover,
      by the time there is enough follow-up to draw conclusions, the data is relatively
      obsolete due to constant improvements in endograft technology and design. Results
      from EVAR have been steadily improving and individualized device selection has
      shown to be valuable. It appears that patients with favorable anatomy do well
      with most modern endografts. Those with challenging anatomies may benefit more
      from a particular design, delivery and deployment feature requiring greater
      knowledge and experience for adequate device selection.

PMID- 20671636
TI  - Current knowledge on E-vita abdominal endograft.
AB  - The field of endovascular abdominal aortic repair has changed remarkably compared
      to what it was prior to 1993, the year of the first commercial endograft
      deployment in the United States. Over the years of endovascular aneurysm repair
      experience, various companies have attempted to construct an ideal stent-graft
      for exclusion of an abdominal aortic aneurysm (AAA). However, it has become
      evident that not all abdominal aortic anatomies are amenable to endovascular
      treatment and that the rationale "one device fits all AAAs" can lead to
      disastrous results. Different endografts have dissimilar properties and
      characteristics. Type of graft material, configuration and type of stent
      structural support, modularity, type of transrenal fixation, are potentially
      influential factors of endograft behavior. The self-expanding E-vita abdominal
      stent-graft (JOTEC, Hechingen, Germany) is a relatively new infrarenal, modular
      stent-graft with suprarenal fixation designed for AAA reconstruction. The present
      paper analyzes the technical characteristics and properties of this device. We
      also analyze our experience with the endoprosthesis and review the current
      literature.

PMID- 20671637
TI  - Recent advances in peripheral in-stent restenosis.

PMID- 20671638
TI  - Mechanical thrombectomy in in-stent restenosis: preliminary experience at the
      iliac and femoropopliteal arteries with the Rotarex System.
AB  - AIM: Iliac and femoropopliteal arterial stenting remains controversial due to
      frequent restenosis. This study aims to evaluate the efficacy of a mechanical
      rotational thrombectomy procedure with the Rotarex Mechanical Thrombectomy System
      (Straub Medical, Wangs, CH) and percutaneous transluminal angioplasty (PTA) in
      terms of technical success, patency rates and limb salvage. METHODS: From May
      2006 to March 2010, 32 selected patients with sub-acute or chronic in-stent
      restenosis at the iliac or femoropopliteal arteries were treated with a Rotarex
      and then PTA procedure. RESULTS: Technical success was 100%. Intra-procedural
      complications included a superficial femoral artery (SFA) dissection (1), SFA (1)
      and external iliac (1) perforations and a groin hematoma (1). There was no
      incidence of embolization in this series. One patient required reintervention
      (3.1%); an attempted surgical bypass and amputation. Secondary reinterventions
      were required in 17 patients (53.1%). Limb salvage rate at 12 months was 90.6%.
      Primary patency at 30 days was 96.8%. Primary, primary assisted and secondary
      patency rates at 6 months were 75%, 75% and 89.6% and at 12 months were 58.1%,
      58.1% and 75.5%, respectively. Late mortality was 18.75% at an average follow-up
      of 13.1 months (3-45) due to the severe disease state of these patients..
      CONCLUSION: This treatment seems promising in terms of technical success and
      embolization risk. Reinterventions are frequently required but mid-term limb
      salvage rates are encouraging. Larger, randomised studies are needed to determine
      the cost/benefit advantage and long-term results.

PMID- 20671639
TI  - Safety and efficacy of directional atherectomy for the treatment of in-stent
      restenosis of the femoropopliteal artery.
AB  - AIM: The aim of this study was to evaluate safety and efficacy of directional
      atherectomy with the Silver HawkTM device as first line treatment for in-stent
      restenosis of the femoropopliteal artery. METHODS: Over a period of 1.5 years in
      stent restenosis of the femoropopliteal artery in 35 lesions (34 legs, 33
      patients) was primarily treated with directional atherectomy. Primary endpoint
      was treatment success (<50% residual stenosis) and the absence of complications.
      Secondary endpoint was target lesion patency after 3, 6 and 12 month assessed by
      duplexsonography. RESULTS: Mean patient age was 70 years (SD+/-10). 74 % were
      claudicants (Rutherford 2-3), 26% had CLI (Ruther-ford (4-5). 45% were diabetics,
      82% had a history of arterial hypertension and nicotine abuse. Mean lesion length
      was 108 mm (SD+/-102 mm). Treatment success with atherectomy alone was achieved
      in 86% with additional PTA (43%) success increased to 97%. Adjunctive stent
      implantation was necessary in 11% of the cases. Post interventional ABI increased
      from 0.54 (+/-0.26) to 0.77 (+/-0.26). The rate of minor complication was 3%
      (1/34) and the rate of major complication was 18% (6/34), mainly due to distal
      embolization. Target lesion patency at 3 month was 86.2%, at 6 month 68% and at
      12 month 25%. CONCLUSIONS: Although atherectomy of in-stent restenosis as a first
      line treatment yields a high initial success rate with a low requirement for
      adjunctive PTA and stent implantation, long term patency rates are low. In our
      study the theoretical advantage of avoiding barotauma did not result in
      prevention of recurrent intimal hyperplasia.

PMID- 20671640
TI  - The potential role of DES in peripheral in-stent restenosis.
AB  - In-stent restenosis (ISR) after non-coronary interventions is becoming an
      increasing clinical and technical problem in daily practice due to the more
      liberal use of stents particularly in femoro-popliteal and infra-popliteal
      interventions. Whereas in the coronaries the role of drug eluting stents (DES) in
      the treatment of ISR is already well defined, very limited data exist about the
      use of DES in the treatment of ISR in non-coronary arteries. So far little data
      is published on the potential role of DES in in-stent restenosis except in renal
      artery interventions. The concept of DES in femoro-popliteal lesions even
      excluding ISR so far failed for sirolimus and everolimus eluting self-expanding
      stents. In infra-popliteal lesions promising single centre reports have already
      been published. Own single center reports showed favorable patency rates for the
      treatment of renal artery ISR. So far, only one study - the Zilver(R) PTX(R)
      single arm study - investigates in a subcohort of 120 of 818 lesions the outcome
      of a paclitaxel eluting DES in treating ISR in femoro-popliteal arteries. The
      Zilver(R) PTX(R) stent consists of a self-expanding nitinol stent platform with a
      polymer free paclitaxel coating with a dose density of 3 mg/mm2. In an interim
      analysis the freedom from target lesion revascularization is 78% after one year.
      Even if not yet having data for primary and secondary patency available, these
      results compare favorably with alternative treatment options such as plain
      balloon angioplasty and cutting balloon angioplasty or even directional
      atherectomy. No data have been published or presented yet about the treatment of
      infra-popliteal ISR. Randomized comparative trials comparing dedicated DES with
      standard interventional techniques such as plain old balloon angioplasty for the
      treatment of ISR in femoro-popliteal and infra-popliteal ISR are mandatory.

PMID- 20671641
TI  - Paclitaxel-coated balloon angioplasty for lower extremity revascularization: a
      new way to fight in-stent restenosis.
AB  - In the last years the development of new techniques and technologies for the
      endovascular treatment of peripheral arterial occlusive disease has allowed to
      treat a vast array of lesions with high technical success and low complications.
      Despite these advances, restenosis, and in particular in-stent restenosis, is a
      problem that significantly affects middle and long-term results and remains to be
      solved. Drug-eluting balloons (DEB) have shown good results in the treatment of
      coronary in-stent restenosis in experimental and clinical trials, but only few
      experimental and clinical trials focus on the peripheral district. This review
      summarizes the available experimental and clinical data in support of DEB in the
      treatment of ISR in the peripheral district. Larger clinical trials focused on
      paclitaxel-coated balloon in the treatment of ISR in the peripheral arteries will
      be necessary to provide definitive evidence of clinical benefit.

PMID- 20671642
TI  - Endovascular brachytherapy with (192)Ir and (188)Re to treat de novo and
      recurrent infrainguinal restenoses.
AB  - We present a review of the literature on endovascular brachytherapy (EVBT) after
      percutaneous transluminal angioplasty (PTA) in the femoropopliteal and tibial
      arteries. The pathophysiological changes induced by PTA and EVBT within the
      vessel wall, technical considerations regarding 192Ir and 188Re, the results of
      clinical trials, and the medication required before, during, and after EVBT are
      summarized.

PMID- 20671643
TI  - The role of stent-grafts for prevention and treatment of restenosis.
AB  - Restenosis rates in the superficial femoral artery remain high in patients
      treated with balloon angioplasty or bare metal stents. Stent-grafts represent an
      alternative endovascular treatment modality for these patients. In the US, the
      only FDA-approved stent-graft for femoral use is the Viabahn endoprosthesis (W.L.
      Gore, Flagstaff, AZ). The Viabahn is constructed of nitinol and ePTFE and has a
      proprietary heparin bioactive surface. Stent-grafts have the potential to reduce
      restenosis by impeding intimal hyperplasia and reducing tissue in-growth;
      however, the problem of edge restenosis has not been eliminated. Graft thrombosis
      remains an important mode of stent-graft failure. The Viabahn has been shown in
      observational studies and randomized trials to be an effective and safe treatment
      strategy compared to bare self-expanding stents and surgical prosthetic bypass
      grafts. Patient and appropriate lesion selection remain important in achieving
      long term patency. In this paper, we review the data surrounding the use of stent
      grafts in the SFA to prevent and treat restenosis. Important technical
      considerations specific to the use of the Viabahn are also discussed.

PMID- 20671644
TI  - Prevention and treatment of in-stent restenosis.
AB  - In-stent restenosis has always been an important issue, since the launch of the
      first stents on the market. The occurrence of in-stent restenosis (ISR) is due to
      two main reasons. First, the presence of stent fractures significantly influences
      restenosis rates. Second, the continuous interaction between the permanently
      implanted artificial material and the vessel tissue, leads to physical
      irritation, long-term endothelial dysfunction, or chronic inflammatory reactions.
      In the Literature only very limited data on ISR treatment in the peripheral
      arteries are available. There are no peer-reviewed publications or studies with
      in-depth follow-up on this specific indication. The underlying reason for this
      probably being that currently available treatments do not yield satisfactory
      results. However, the continuing search for better solutions and the
      technological evolution lead to the introduction of the Viabahn with PROPATEN
      coating, DES and DCB, which may result in the first promising treatment options
      for ISR.

PMID- 20671645
TI  - Avenues to prevent venous insufficiency.

PMID- 20671646
TI  - Catheter-directed thrombolysis in the treatment of iliofemoral venous thrombosis.
      A review.
AB  - Patients with acute iliofemoral venous thrombosis treated with anticoagulation
      only are at high risk of developing postthrombotic syndrome. Immediate removal of
      the thrombus by catheter-directed thrombolysis (CDT) may increase patency,
      prevent damage of the venous valves, and prevent reflux and PTS. However, the
      indications for its use are not well established because of lack of data from
      randomised controlled trials. Aim of this review was to describe the treatment of
      iliofemoral venous thrombosis with CDT and to evaluate the effectiveness of this
      therapy. An electronic literature search was performed in the PubMed, EMBASE, and
      Cochrane Library on the largest studies (more than 40 legs treated) concerning
      catheter-directed thrombolysis of iliofemoral venous thrombosis. A total of 236
      publications were identified but only 11 studies met the inclusion criteria with
      a total of 979 lower limbs. Early patency from 6-12 months was 60-95% and patency
      after six years was 82%, reported in one study. Mortality of up to 1% was
      reported in two studies. Major complications such as hematomas requiring surgery
      were observed in 1-11% whereas minor complications, mostly bleeding from the
      puncture site, were seen in up to 18%. CDT seems to be effective in the treatment
      of iliofemoral venous thrombosis and results are promising. Studies are, however,
      characterized by heterogeneity and are difficult to compare. Only one study
      reports long-term follow-up and incidence of postthrombotic syndrome is not
      reported. Further studies regarding the use of CDT, both alone and in combination
      with mechanical thrombectomy are needed.

PMID- 20671647
TI  - Endovenous radiofrequency ablation of saphenous vein reflux. The VNUS Closure
      procedure with Closurefast. An updated review.
AB  - Endovenous treatment is progressively supplanting open surgery in treatment of
      saphenous reflux. Among the emerging techniques the VNUS Closure, procedure with
      ClosureFast is one of the most promising. The aim of the presente review is to
      remind the principle of radiofrequency action in varicose vein treatment, to
      describe the procedure achievement including the devices used generator and
      catheter and finally to report the published studies on ClosureFast. A research
      in the published literature identified only two articles reporting the outcome of
      procedure. The first one, a prospective, non-randomized international multicenter
      prospective clinical trial includes 296 great saphenous veins treated by
      radiofrequency with the ClosureFAST catheter under tumescent anesthesia.
      Occlusion rate at 6 months (62 extremities) was achieved in 99.6% with no
      recanalisation since the first ultrasound assessment at 3 days. The Venous
      Clinical Severity Score was significantly improved at 6 months compared with the
      baseline one. No serious adverse events were reported. The second one RECOVERY
      trial was a multicenter prospective randomized comparative clinical trial of the
      ClosureFAST catheter and endovenous 980-nm laser ablation including 69 patients.
      Final results showed patients treated with the ClosureFAST catheter experienced
      significantly less post-procedure pain, bruising and tenderness when compared to
      laser ablation, There were statistically fewer complications in limbs treated
      with the ClosureFAST catheter compared to laser ablation (P=0.021). In conclusion
      radiofrequency segmental thermal ablation with ClosureFAST catheter is feasible,
      safe, and well tolerated. Procedure is shortened and short-term results are
      better than those provided by the previous Closure catheter. A randomized control
      trial ClosureFAST versus endovenous laser is in favour of the first one.

PMID- 20671648
TI  - Isolated pharmacomechanical thrombolysis of deep venous thrombosis utilizing a
      peripheral infusion system: Manuf.
AB  - AIM: The aim of this paper was to prospectively monitor the performance of an
      isolated pharmacomechanical thrombolysis (IPMT) device, the Trellis(R) Peripheral
      Infusion System, through a company-sponsored registry. METHODS: Demographic,
      thrombus characterization, and procedural data were collected on the treatment of
      2203 extremity deep venous thrombosis (DVTs) in 2024 patients via case-report
      forms submitted by the treating physicians. Data were analyzed using simple
      accrual and percentages. RESULTS: Patients averaged 53 (+/-18) years of age and
      were 49% female. Thrombi were located in the iliofemoral (25.1%); iliofemoral to
      popliteal (19.3%); inferior vena cava (IVC) only or IVC and infrainguinal lower
      extremity (18.7%); femoral to popliteal (12.2%); isolated femoral (6%), iliac
      (6%) or popliteal (0.6%); and upper extremity (12.1%). Thrombus chronicity was
      reported as acute in 34.5% (N=760), acute-on-chronic in 41.5% (N=914), subacute
      in 10.4% (N=230), subacute-on-chronic in 9.8% (N=216), and chronic in 3.8%
      (N=83). The thrombolytic agent chosen by the physician most often was tissue
      plasminogen activator (tPA; 95.8%) at an average total dose per patient of 14.9
      +/-8.3 mg. Combined Grade III and II venous patency following treatment across
      all thrombus chronicities was 95.5% and was achieved in a single setting in 83.3%
      (N=1753) of patients. Average IPMT run time per procedure was 22.3 +/-9.4
      minutes. Sixteen percent of patients' limbs required additional catheter-directed
      thrombolysis (CDT); 75% required angioplasty and/or stent. No major bleeding
      complications, symptomatic pulmonary embolism (PE), or other significant adverse
      events occurred during the procedures. CONCLUSION: IPMT is an effective
      therapeutic option for the acute management of extremity DVT. Low lytic doses and
      short infusion times are associated with a lower risk of bleeding than with CDT.
      Rapid restoration of patency may be associated with sustained valve function and
      a decreased incidence of post-thrombotic syndrome.

PMID- 20671649
TI  - Risk factors for residual thrombotic occlusion after proximal deep vein
      thrombosis of the legs.
AB  - AIM: Residual thrombotic occlusion (RTO) after deep vein thrombosis (DVT) is
      considered as a risk factor of recurrent venous thromboembolism (VTE). We
      searched for risk factors associated with RTO after proximal DVT at the lower
      extremities. METHODS: Using compression ultrasound, we evaluated the presence of
      RTO at 6 months after DVT (RTO defined as a residual thrombus occupying, at
      maximum compressibility, >/=20% of the vein lumen before compression). RESULTS:
      We examined 126 Czech patients: mean age 57.5 years; 50.0% women, 68.3% femoral
      location of DVT (otherwise popliteal), RTO found in 45.2%. While accounting for
      covariates, in the whole population, RTO was significantly associated with
      following factors: (OR; 95% confidence limit; p value): male sex (2.01; 1.27
      3.19; P=0.003), femoral location (2.76; 1.59-4.78; P=0.0003). In women, but not
      in men, an association was demonstrated for: concurrent pulmonary embolism (PE)
      (18.51; 1.85-185.7; P=0.0131), diabetes mellitus (4.62; 1.38-15.51; P=0.0133) and
      statin use (0.11; 0.02-0.62; P=0.0125). In contrast, in men RTO was associated
      with an unprovoked DVT (2.6; 1.26-5.34; P=0.0094). CONCLUSION: In the whole study
      population, male sex and femoral location of DVT were positively associated with
      RTO. In women, concurrent PE and diabetes mellitus were risk factors for RTO,
      while the use of statins was a protective factor. There was a positive
      association between RTO and unprovoked DVT in men. These findings deserve further
      evaluation in a larger study.

PMID- 20671650
TI  - Correlation between the intensity of venous reflux in the saphenofemoral junction
      and morphological changes of the great saphenous vein by duplex scanning in
      patients with primary varicosis.
AB  - AIM: One of the major causes of chronic venous disease is venous reflux, the
      identification and quantification of which are important for diagnosis. Duplex
      scanning allows for the detection and quantification of reflux in individual
      veins. Evaluation of the great saphenous vein in primary varicosis is necessary
      for its preservation. Objective of the study is to evaluate a possible
      correlation between the intensity of reflux at the saphenofemoral junction,
      diameter alterations of the incompetent great saphenous vein and the practical
      effect of such correlation. Also to compare the clinical severity of the CEAP
      classification with such parameters. METHODS: Three hundred limbs were submitted
      to duplex evaluation of their insufficient saphenous veins. Vein diameter was
      measured on five different points. Velocity and flow at reflux peak and reflux
      time were determined. The saphenous vein's diameters were correlated with
      velocity, flow and time. The three latter parameters and diameters were compared
      with clinical severity according to CEAP. RESULTS: Correlation was found between
      the saphenous vein's diameters, velocity and flow. No correlation was observed
      between time and diameter in the thigh's upper and middle thirds. When comparing
      diameter, velocity and flow with CEAP clinical severity classification, an
      association was observed. The correlation between reflux time with clinical
      severity was weak. CONCLUSION: Reflux time is a good parameter for identifying
      the presence of reflux, but not for quantifying it. Velocity and peak flow were
      better parameters for evaluating reflux intensity as they were correlated with
      great saphenous vein alterations, and were associated with the disease's clinical
      severity.

PMID- 20671651
TI  - High MAPK p38 activity and low level of IL-10 in intermittent claudication as
      opposed to stable angina.
AB  - AIM: The aim of the present pilot study was to relate the activity of MAPK p38
      with the levels of pro- and anti-inflammatory cytokines in a small cohort of
      patients with either stable angina (N=5) or intermittent claudication (N=5)
      compared to healthy controls (N=10). METHODS: The activity of MAPK p38 was
      determined in peripheral blood mononuclear cells, isolated from whole blood by
      western blot using phospho-specific anti-MAPK p38 antibodies. Cytokine levels of
      11 pro- and anti-inflammatory cytokines were determined from the serum using flow
      cytometry. RESULTS: We found a significant elevation of the MAPK p38 activity in
      the intermittent claudication group (P=0.0027) compared with the healthy control
      group whereas the stable angina group showed similar MAPK p38 activity as the
      healthy control group. The IL-10 level in serum found in the stable angina group
      was significantly higher compared with both the healthy control group (P=0.0116)
      and the intermittent claudication group (P=0.0317). CONCLUSION: Our results imply
      that there is a casual relationship between increased levels of the anti
      inflammatory cytokines IL-10 and IL-4 and the activity of the MAPK p38. Possibly
      has IL-10 a protective role that down-regulates the activity of MAPK p38 and
      thereby further inflammatory processes in stable angina patients.

PMID- 20671652
TI  - Atorvastatin therapy is associated with improvement of oxidized low-density
      lipoprotein cholesterol levels, which correlates with the degree of stenosis in
      patients with carotid atheromatosis with and without prior angioplasty.
AB  - AIM: Oxidized low-density lipoprotein (oxLDL) is a pivotal factor of the
      atheromatous process. Statins reduce atheromatosis and cardiovascular risk. The
      aim of the present study was to investigate the effect of statin therapy on
      circulating oxLDL and the possible impact of such effect on stenosis due to
      carotid artery atheromatosis. METHODS: A total of 100 patients (76 males, median
      age 68 years) with carotid atheromatosis were enrolled. Those with stenosis >70%
      (n=50) were pre-treated with carotid angioplasty, whereas those with <70% were
      treated conservatively. Both groups were given low-dose atrorvastatin, tittered
      to maintain LDL cholesterol <100 mg/dL. Anthropometrics, complete lipid profile,
      and oxLDL were obtained in 1, 3, 6 and 12 months. Stenosis was evaluated by
      ultrasonography at baseline and 12 months. RESULTS: Lipid profile significantly
      improved at 12 months and oxLDL fell from 62.26+/-22.03 mg/dL at baseline to
      44.49+/-21.75 mg/dL at 12 months (P<0.001). In the invasively pretreated group no
      restenosis was noticed; in the conservatively treated group a significant
      reduction of stenosis was demonstrated (47.6+/-13.2% vs 37.7+/-15.7%, P<0.001).
      The decrease of oxLDL correlated with the reduction of stenosis (r=0.17,
      P=0.018). In multivariate analysis, oxLDL was an independent risk factor for re
      stenosis (hazard ratio=4.319, P<0.001). CONCLUSION: A marked reduction of oxLDL
      was shown in patients with carotid atheromatosis treated with low-dose
      atorvastatin. Moreover, oxLDL could be a measure of the degree of stenosis in
      such patients.

PMID- 20671653
TI  - Relationship between education and atherosclerotic disease risk factors in
      patients with peripheral arterial disease.
AB  - AIM: The aim of the present study was to investigate whether different levels of
      education are associated with different atherosclerotic disease risk factors.
      METHODS: The cross-sectional study, involving 388 consecutive patients with
      verified peripheral arterial disease, was performed in Belgrade. Formal education
      level was used as a proxy for socioeconomic status. Anthropometric parameters and
      data on cardiovascular risk factors were analyzed in participants with different
      levels of education. In the analysis, univariate and multivariate logistic
      regressions were used. RESULTS: Multivariate analysis showed that low education
      was significantly positively related to alcohol consumption (Odds Ratio - OR,
      4.67; 95% confidence interval - CI, 1.80-12.12), increased triglycerides (OR,
      2.73; 95% CI, 1.13-6.61), and physical activity during work (OR, 43.10; 95% CI
      14.37-129.28), and negatively related to former smoking (OR, 0.11; 95% CI, 0.03
      0.46) and sports and leisure - time physical activity (OR, 0.13; 95% CI, 0.04
      0.41 and OR, 0.25; 95% CI, 0.11-0.57). Medium education was significantly
      positively related to increased triglycerides (OR, 1.74; 95% CI 1.01-2.98) and
      increased LDL-cholesterol (OR 2.37; 95% CI, 1.35-4.18), and to physical activity
      during work (OR, 2.22; 95% CI, 1.34-3.67), and negatively related to age (OR,
      0.95; 95% CI, 0.92-0.98) and leisure - time physical activity (OR, 0.47; 95% CI,
      0.30-0.74). CONCLUSION: It can be concluded that if there are differences in the
      risk of the occurrence of peripheral arterial disease by education status, they
      could be only partly explained by differences in the observed atherosclerotic
      disease risk factors.

PMID- 20671654
TI  - Modification of the lipidic and coagulative pattern in postmenopause women:
      effect of hormone replacement therapy.
AB  - AIM: We evaluated the changes of lipidic and coagulative pattern during menopause
      and the influence of hormone replacement therapy (HRT) on these parameters.
      METHODS: We considered 158 patients divided into 2 groups: Group I consisted of
      127 women in physiological/surgical menopause and Group II of 31 women with
      childbearing potential. Subsequently, we considered a group III formed of 34
      patients from menopausal women (group I) who underwent three months of HRT. We
      evaluated total-cholesterol (TC), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL
      C), triglycerides (TG), lipoprotein (a) (Lpa), fibrinogen, antithrombin III
      (ATIII), factor VII (FVII) and tissue factor pathway inhibitor (TFPI). RESULTS:
      We found a worse lipid profile in the post-menopausal group compared to controls
      (TC 243.8+/-29.7 vs 217.9+/-32.7 mg%, P=0.002; TG 121.5+/-68.4 vs 88.6+/-53.0
      mg%, P=0.039; LDL-C 163.0+/-27.9 vs 136.2+/-29.6 mg%, P=0.004; HDL-C 60.9+/-14.9
      vs 64.1+/-14.6 mg%, P=ns). With regard to the coagulative pattern, fibrinogen was
      significantly higher in the post-menopausal group (fibrinogen: 273.3+/-67.4 vs
      243.8+/-39.5 mg%, P=0.013; ATIII 112.2+/-11.7 vs 117.5+/-12.7% %, P=0.059; FVII
      121.6+/-11.3 vs 117.6+/-10.8 mg%, P=ns; TFPI activity 2.5+/-2.3 vs 2.1+/-1.1
      U/mL, P=ns; TFPI antigen 120+/-38 vs 127+/-39 U/mL, P=ns). Comparing the same
      parameters, before and after three months of HRT, in patients of Group III we
      observed a significant improvement of TC and TG levels (TC from 232.3+/-42.7 to
      215.2+/-37.6 mg%, P=0.0001; TG from 103.7+/-56.8 to 95.0+/-44.3 mg%, P=0.059; HDL
      C from 62.3+/-12.9 to 63.6+/-12.6 mg%, P=ns; LDL-C from 149.3+/-38.7 to 132.6+/
      34.5 mg%, P=0.0001). The following changes were observed with regard to
      coagulative parameters: fibrinogen from 270.9+/-69.4 to 253.2+/-56.2 mg%, P=0.07;
      ATIII from 113.5+/-11.4 to 110.8+/-13.2 mg%, P=0.198; FVII from 108.6+/-18.0 to
      104.4+/-17.5 mg%, 0.014. TFPI activity from 2.6+/-2.3 to 2.3+/-1.4 U/ml, P=ns;
      TFPI antigen from 68+/-13 to 87+/-22 U/mL, P=0.001. CONCLUSION: Our data confirm
      the presence of an alteration in lipidic and coagulative pattern in post
      menopausal women and positive changes after HRT.

PMID- 20671655
TI  - Impaired peripheral micro- and macrocirculation during hemodialysis in uremic
      patients.
AB  - AIM: Acute hemodynamic changes during hemodialysis may jeopardize the peripheral
      blood circulation in patients with end-stage renal disease (ESRD). The aim of the
      present study was to investigate the effects of three consecutive hemodialyses on
      peripheral micro- and macrocirculation in patients with ESRD. METHODS: Twenty
      patients with ESRD were investigated, i.e. 10 diabetic and 10 non-diabetic
      patients, before and during three consecutive hemodialysis during one week. Skin
      microcirculation was evaluated by transcutaneous oxygen tension (tcPO2) at the
      chest and foot levels, and maximum microvascular hyperemia (MMH) at the foot by
      laser Doppler fluxmetry before and during local warming of skin to 44 oC.
      Macrocirculation was measured by systolic and diastolic arm blood pressure (BP),
      and by systolic toe BP. RESULTS: MMH, tcPO2 (foot) and tcPO2 (chest) decreased
      significantly (P=0.01) during hemodialysis, and so did systolic arm BP and toe BP
      (P=0.02). No significant differences were found between the different
      hemodialysis days, nor between the diabetic and non-diabetic patients.
      CONCLUSION: The study shows that peripheral micro- and macrocirculation are
      impaired during hemodialysis in patients with ESRD. The effects of hemodialysis
      on peripheral blood perfusion are reproducible, and the same reaction pattern was
      seen in diabetic and non-diabetic patients. Patients with peripheral arterial
      occlusive disease seem more susceptible to BP reduction during hemodialysis, and
      in some patients toe BP and tcPO2 (foot) decreased to levels indicating high risk
      of gangrene.

PMID- 20671657
TI  - Ethical and legal aspects on the use of images and photographs in medical
      teaching and publication.
AB  - The aim of the study was to investigate the legal and ethical concerns raised
      from the use of photographs and images in medical publication. A search in the
      pertinent literature was performed. It is of paramount importance that the
      patient's autonomy, privacy and confidentiality is respected. In all cases in
      which photographs and images contain identifiable information patient's consent
      for any potential use of this material is mandatory. Patients should be aware
      that with the evolution of electronic publication, once an image is published,
      there is no efficient control of its future misuse. Physicians and hospitals have
      a duty to use with confidentiality any material kept in the patient's medical
      records. Efforts should be made to anonymised images and photographs used in
      teaching and publication so that such information does not raise ethical and
      legal concerns. The procedures for using photographs and images in medical
      publication and teaching should respect the ethical principles and contain only
      anonymous information to avoid legal consequences. Continuous scrutiny and reform
      is required in order to adapt to the changing social and scientific environment.

PMID- 20671656
TI  - Serum high-density and low-density lipoprotein cholesterol is associated with
      abdominal aortic aneurysm presence: a systematic review and meta-analysis.
AB  - AIM: To summarize the present evidence for an association between high-density
      lipoprotein (HDL) or low-density lipoprotein (LDL) cholesterol and abdominal
      aortic aneurysm (AAA) presence, we performed a systematic review and meta
      analysis of case-control studies that compared serum HDL or LDL cholesterol
      between patients with AAA and control subjects. METHODS: MEDLINE and EMBASE
      databases were searched to identify all case-control studies that compared serum
      HDL or LDL cholesterol between patients with AAA and control subjects. For each
      study, data regarding serum HDL or LDL cholesterol in both the AAA and control
      groups were used to generate mean differences (MDs) and 95% confidence intervals
      (CIs). Study-specific estimates were combined using inverse variance-weighted
      average of logarithmic MDs in both fixed- and random-effects models. RESULTS: Our
      search identified 8 eligible studies including 812 patients with AAA and 8 267
      control subjects. Pooled analysis demonstrated significantly lower serum HDL
      cholesterol (MD, -0.15 mmol/L; 95% CI, -0.24 to -0.07 mmol/L; P=0.0006) and
      significantly higher serum LDL cholesterol (MD, 0.25 mmol/L; 95% CI, 0.08 to 0.42
      mmol/L; P=0.004) in the AAA group than those in the control group in random
      effect models. There was significant study heterogeneity of results but no
      evidence of significant publication bias. Several sensitivity analyses did not
      substantively alter the overall result of our analysis. CONCLUSION: We found
      that, based on a systematic review and meta-analysis, serum HDL cholesterol is
      likely lower and serum LDL cholesterol is likely higher in patients with AAA than
      control subjects. Lower serum HDL cholesterol and higher serum LDL cholesterol
      may be associated with AAA presence.

PMID- 20671658
TI  - Acute carotid occlusion and stroke due to antiphospholipid antibody syndrome:
      case report and literature review.
AB  - Neurologic events associated to antiphospholipoid syndrome (APLS) are not
      uncommon, but ischemic stroke due to acute carotid thrombosis, is a rare
      presentation of this syndrome. We report a case of a 48 years old female patient,
      without evidence of atherothrombosis or other vascular pathology, who presented
      an ischemic stroke due to acute thrombosis of the left internal carotid artery.
      The occlusion was diagnosed by Duplex scan and magnetic resonance angiography
      (Ds+MRA). The patient was anticoagulated and experienced total regression of her
      neurologic symptoms after a week. Ds+MRA were performed again and confirmed re
      establishment of normal flow of internal carotid artery. A thorough clinical
      investigation confirmed the diagnosis of APLS (the association of a major
      thombotic event and high anticardiolipoid IgG antibody titers in three blood
      samples). The patient has been submitted to oral anticoagulation for three years
      and has not experienced new neurologic or thrombotic events.

PMID- 20671659
TI  - Agenesis of the renal segment of inferior vena cava associated with venous
      stasis.
AB  - Congenital anomalies of the inferior vena cava is an extremely rare vascular
      anomaly with controversial pathogenesis. Anomalies of the inferior vena cava
      (IVC) are present in 0.3% to 0.5% of otherwise healthy individual and in 0.6% to
      2% of patients with other cardiovascular defects. The phenomenon of absence of
      the IVC has been described in a variety of ways such as absence, agenesis,
      anomalous, and interruption of a particular segment ([infra] hepatic, prerenal,
      renal, or infrarenal) of the IVC. We describe a 42-year-old man with chronic
      venous insufficiency, without DVT, caused by congenital absence of renal segment
      of the IVC.

PMID- 20671660
TI  - Proportion of workers who were work-injured and payment by workers' compensation
      systems - 10 states, 2007.
AB  - Work-related injuries are a major cause of morbidity in the United States, with
      approximately 4 million employer-reported nonfatal injuries and illnesses in
      2007. Currently, few population-based state-level estimates of nonfatal
      occupational injury rates exist. In the few extant studies, self-reported,
      nonfatal occupational injury rates exceed estimates based on employer reports or
      state workers' compensation systems. To estimate the proportion of workers who
      were work-injured during the preceding 12 months and the proportion of those
      injured for whom workers' compensation insurance programs paid for medical care,
      10 states added a module to their 2007 Behavioral Risk Factor Surveillance System
      (BRFSS) survey. This report summarizes the results of that survey, which found
      that the proportion of workers who were work-injured during the preceding 12
      months ranged from 4.0 to 6.9 work-injured persons per 100 employed persons
      (Kentucky and New York, respectively). The proportion of self-reported work
      injured persons for whom medical treatment was paid by workers' compensation
      insurance ranged from 47% in Texas to 77% in Kentucky. This study shows the
      feasibility of complementing existing occupational injury surveillance through
      the use of population-based surveys. States that wish to enhance existing
      occupational injury surveillance should consider similar studies. Additional
      research is needed to understand the reasons for nonpayment of worker-reported
      occupational injuries by workers' compensation insurance programs.

PMID- 20671661
TI  - Update: influenza activity - United States, 2009-10 season.
AB  - During the 2009-10 influenza season, the second wave of influenza activity from
      2009 pandemic influenza A (H1N1) occurred in the United States; few seasonal
      influenza viruses were detected. Influenza activity peaked in late-October and
      was associated with higher pediatric mortality and higher rates of
      hospitalizations in children and young adults than in previous seasons. The
      proportion of visits to health-care providers for influenza-like illness (ILI),
      as reported in the U.S. Outpatient Influenza-like Illness Surveillance Network
      (ILINet), was among the highest since ILI surveillance began in 1997 in its
      current form. This report summarizes influenza activity in the United States
      during the 2009-10 influenza season (August 30, 2009-June 12, 2010).

PMID- 20671662
TI  - Regional influenza A (H1N1) 2009 monovalent vaccination campaign - Skokie,
      Illinois, October 16-December 31, 2009.
AB  - On July 29, 2009, the Advisory Committee on Immunization Practices (ACIP)
      recommended a phased approach for administration of influenza A (H1N1) 2009
      monovalent vaccine, with certain high-risk groups in the United States receiving
      the first doses. In Illinois, state authorities gave responsibility for initial
      vaccine administration to local health departments and hospitals. This report
      describes the vaccination campaign of the Skokie Health Department (SHD), during
      October 16-December 31, 2009. The SHD campaign initially was planned to cover the
      67,000 persons residing in Skokie only, but that plan was expanded on November 4,
      when, in response to a nationwide vaccine shortage, the state health director
      urged local health departments to vaccinate any person in the ACIP priority
      groups regardless of jurisdictional boundaries. SHD, with the assistance of 1,075
      volunteers, either administered or distributed to medical providers 40,850 H1N1
      vaccine doses during a 9-week period, including 8,904 doses administered at 52
      Skokie schools and day-care facilities, and 12,876 doses at mass vaccination
      clinics visited by residents of 193 of the 1,313 Illinois municipalities. At the
      time of the campaign, widespread illness from 2009 H1N1 in Illinois, with highly
      publicized deaths, contributed to a public sense of urgency about vaccination.
      Consistent with published studies, mass clinics in Skokie were an effective means
      to vaccinate large populations rapidly. The campaign highlighted the need for
      flexible plans, including the possibility of vaccinating persons who resided well
      beyond SHD's jurisdictional borders.

PMID- 20671663
TI  - Yellow fever vaccine: recommendations of the Advisory Committee on Immunization
      Practices (ACIP).
AB  - This report updates CDC's recommendations for using yellow fever (YF) vaccine
      (CDC. Yellow fever vaccine: recommendations of the Advisory Committee on
      Immunizations Practices: MMWR 2002;51[No. RR-17]). Since the previous YF vaccine
      recommendations were published in 2002, new or additional information has become
      available on the epidemiology of YF, safety profile of the vaccine, and health
      regulations related to the vaccine. This report summarizes the current
      epidemiology of YF, describes immunogenicity and safety data for the YF vaccine,
      and provides recommendations for the use of YF vaccine among travelers and
      laboratory workers. YF is a vectorborne disease resulting from the transmission
      of yellow fever virus (YFV) to a human from the bite of an infected mosquito. It
      is endemic to sub-Saharan Africa and tropical South America and is estimated to
      cause 200,000 cases of clinical disease and 30,000 deaths annually. Infection in
      humans is capable of producing hemorrhagic fever and is fatal in 20%-50% of
      persons with severe disease. Because no treatment exists for YF disease,
      prevention is critical to lower disease risk and mortality. A traveler's risk for
      acquiring YFV is determined by multiple factors, including immunization status,
      location of travel, season, duration of exposure, occupational and recreational
      activities while traveling, and local rate of virus transmission at the time of
      travel. All travelers to countries in which YF is endemic should be advised of
      the risks for contracting the disease and available methods to prevent it,
      including use of personal protective measures and receipt of vaccine.
      Administration of YF vaccine is recommended for persons aged >or=9 months who are
      traveling to or living in areas of South America and Africa in which a risk
      exists for YFV transmission. Because serious adverse events can occur following
      YF vaccine administration, health-care providers should vaccinate only persons
      who are at risk for exposure to YFV or who require proof of vaccination for
      country entry. To minimize the risk for serious adverse events, health-care
      providers should observe the contraindications, consider the precautions to
      vaccination before administering vaccine, and issue a medical waiver if
      indicated.

PMID- 20671664
TI  - How to feed a hungry world.
AB  - Producing enough food for the world's population in 2050 will be easy. But doing
      it at an acceptable cost to the planet will depend on research into everything
      from high-tech seeds to low-tech farming practices.

PMID- 20671665
TI  - Save the census.
AB  - The Canadian government should rethink its decision to change the way census data
      are collected.

PMID- 20671678
TI  - Freedom of spill research threatened.

PMID- 20671679
TI  - Therapeutic HIV vaccines show promise.

PMID- 20671680
TI  - Retraction recommended for enzyme-chip paper.

PMID- 20671681
TI  - A closer look at cosmic impacts.

PMID- 20671682
TI  - US seeks solar flair for fuels.

PMID- 20671683
TI  - US charges scientist with economic espionage.

PMID- 20671684
TI  - Fears over Europe's GM crop plan.

PMID- 20671686
TI  - Protein mapping gains a human focus.

PMID- 20671687
TI  - Food: The growing problem.

PMID- 20671688
TI  - Food: Inside the hothouses of industry.

PMID- 20671689
TI  - Food: An underground revolution.

PMID- 20671690
TI  - Food: The global farm.

PMID- 20671691
TI  - Monitoring the world's agriculture.
AB  - To feed the world without further damaging the planet, Jeffrey Sachs and 24
      foodsystem experts call for a global data collection and dissemination network to
      track the myriad impacts of different farming practices.

PMID- 20671692
TI  - Regulation must be revolutionized.
AB  - Unjustified and impractical legal requirements are stopping genetically
      engineered crops from saving millions from starvation and malnutrition, says Ingo
      Potrykus.

PMID- 20671694
TI  - European Commission clarifies the rules for research audits.

PMID- 20671696
TI  - Regenerative medicine: An eye to treating blindness.

PMID- 20671697
TI  - Earthquakes: Climate and intraplate shocks.

PMID- 20671698
TI  - Oceanography: Century of phytoplankton change.

PMID- 20671700
TI  - Condensed-matter physics: Bringing the noise.

PMID- 20671699
TI  - Metabolism: Tick, tock, a beta-cell clock.

PMID- 20671701
TI  - The four hundred years of planetary science since Galileo and Kepler.
AB  - For 350 years after Galileo's discoveries, ground-based telescopes and
      theoretical modelling furnished everything we knew about the Sun's planetary
      retinue. Over the past five decades, however, spacecraft visits to many targets
      transformed these early notions, revealing the diversity of Solar System bodies
      and displaying active planetary processes at work. Violent events have punctuated
      the histories of many planets and satellites, changing them substantially since
      their birth. Contemporary knowledge has finally allowed testable models of the
      Solar System's origin to be developed and potential abodes for extraterrestrial
      life to be explored. Future planetary research should involve focused studies of
      selected targets, including exoplanets.

PMID- 20671702
TI  - Observation of neutral modes in the fractional quantum Hall regime.
AB  - The quantum Hall effect takes place in a two-dimensional electron gas under a
      strong magnetic field and involves current flow along the edges of the sample.
      For some particle-hole conjugate states of the fractional regime (for example,
      with fillings between 1/2 and 1 of the lowest Landau level), early predictions
      suggested the presence of counter-propagating edge currents in addition to the
      expected ones. When this did not agree with the measured conductance, it was
      suggested that disorder and interactions will lead to counter-propagating modes
      that carry only energy--the so called neutral modes. In addition, a neutral
      upstream mode (the Majorana mode) was expected for selected wavefunctions
      proposed for the even-denominator filling 5/2. Here we report the direct
      observation of counter-propagating neutral modes for fillings of 2/3, 3/5 and
      5/2. The basis of our approach is that, if such modes impinge on a narrow
      constriction, the neutral quasiparticles will be partly reflected and fragmented
      into charge carriers, which can be detected through shot noise measurements. We
      find that the resultant shot noise is proportional to the injected current.
      Moreover, when we simultaneously inject a charge mode, the presence of the
      neutral mode was found to significantly affect the Fano factor and the
      temperature of the backscattered charge mode. In particular, such observations
      for filling 5/2 may single out the non-Abelian wavefunctions for the state.

PMID- 20671703
TI  - Global phytoplankton decline over the past century.
AB  - In the oceans, ubiquitous microscopic phototrophs (phytoplankton) account for
      approximately half the production of organic matter on Earth. Analyses of
      satellite-derived phytoplankton concentration (available since 1979) have
      suggested decadal-scale fluctuations linked to climate forcing, but the length of
      this record is insufficient to resolve longer-term trends. Here we combine
      available ocean transparency measurements and in situ chlorophyll observations to
      estimate the time dependence of phytoplankton biomass at local, regional and
      global scales since 1899. We observe declines in eight out of ten ocean regions,
      and estimate a global rate of decline of approximately 1% of the global median
      per year. Our analyses further reveal interannual to decadal phytoplankton
      fluctuations superimposed on long-term trends. These fluctuations are strongly
      correlated with basin-scale climate indices, whereas long-term declining trends
      are related to increasing sea surface temperatures. We conclude that global
      phytoplankton concentration has declined over the past century; this decline will
      need to be considered in future studies of marine ecosystems, geochemical
      cycling, ocean circulation and fisheries.

PMID- 20671704
TI  - Pinning quantum phase transition for a Luttinger liquid of strongly interacting
      bosons.
AB  - Quantum many-body systems can have phase transitions even at zero temperature;
      fluctuations arising from Heisenberg's uncertainty principle, as opposed to
      thermal effects, drive the system from one phase to another. Typically, during
      the transition the relative strength of two competing terms in the system's
      Hamiltonian changes across a finite critical value. A well-known example is the
      Mott-Hubbard quantum phase transition from a superfluid to an insulating phase,
      which has been observed for weakly interacting bosonic atomic gases. However, for
      strongly interacting quantum systems confined to lower-dimensional geometry, a
      novel type of quantum phase transition may be induced and driven by an
      arbitrarily weak perturbation to the Hamiltonian. Here we observe such an effect-
      the sine-Gordon quantum phase transition from a superfluid Luttinger liquid to a
      Mott insulator--in a one-dimensional quantum gas of bosonic caesium atoms with
      tunable interactions. For sufficiently strong interactions, the transition is
      induced by adding an arbitrarily weak optical lattice commensurate with the
      atomic granularity, which leads to immediate pinning of the atoms. We map out the
      phase diagram and find that our measurements in the strongly interacting regime
      agree well with a quantum field description based on the exactly solvable sine
      Gordon model. We trace the phase boundary all the way to the weakly interacting
      regime, where we find good agreement with the predictions of the one-dimensional
      Bose-Hubbard model. Our results open up the experimental study of quantum phase
      transitions, criticality and transport phenomena beyond Hubbard-type models in
      the context of ultracold gases.

PMID- 20671705
TI  - Direct generation of photon triplets using cascaded photon-pair sources.
AB  - Non-classical states of light, such as entangled photon pairs and number states,
      are essential for fundamental tests of quantum mechanics and optical quantum
      technologies. The most widespread technique for creating these quantum resources
      is spontaneous parametric down-conversion of laser light into photon pairs.
      Conservation of energy and momentum in this process, known as phase-matching,
      gives rise to strong correlations that are used to produce two-photon
      entanglement in various degrees of freedom. It has been a longstanding goal in
      quantum optics to realize a source that can produce analogous correlations in
      photon triplets, but of the many approaches considered, none has been technically
      feasible. Here we report the observation of photon triplets generated by cascaded
      down-conversion. Each triplet originates from a single pump photon, and therefore
      quantum correlations will extend over all three photons in a way not achievable
      with independently created photon pairs. Our photon-triplet source will allow
      experimental interrogation of novel quantum correlations, the generation of
      tripartite entanglement without post-selection and the generation of heralded
      entangled photon pairs suitable for linear optical quantum computing. Two of the
      triplet photons have a wavelength matched for optimal transmission in optical
      fibres, suitable for three-party quantum communication. Furthermore, our results
      open interesting regimes of non-linear optics, as we observe spontaneous down
      conversion pumped by single photons, an interaction also highly relevant to
      optical quantum computing.

PMID- 20671706
TI  - Following a chemical reaction using high-harmonic interferometry.
AB  - The study of chemical reactions on the molecular (femtosecond) timescale
      typically uses pump laser pulses to excite molecules and subsequent probe pulses
      to interrogate them. The ultrashort pump pulse can excite only a small fraction
      of molecules, and the probe wavelength must be carefully chosen to discriminate
      between excited and unexcited molecules. The past decade has seen the emergence
      of new methods that are also aimed at imaging chemical reactions as they occur,
      based on X-ray diffraction, electron diffraction or laser-induced recollision-
      with spectral selection not available for any of these new methods. Here we show
      that in the case of high-harmonic spectroscopy based on recollision, this
      apparent limitation becomes a major advantage owing to the coherent nature of the
      attosecond high-harmonic pulse generation. The coherence allows the unexcited
      molecules to act as local oscillators against which the dynamics are observed, so
      a transient grating technique can be used to reconstruct the amplitude and phase
      of emission from the excited molecules. We then extract structural information
      from the amplitude, which encodes the internuclear separation, by quantum
      interference at short times and by scattering of the recollision electron at
      longer times. The phase records the attosecond dynamics of the electrons, giving
      access to the evolving ionization potentials and the electronic structure of the
      transient molecule. In our experiment, we are able to document a temporal shift
      of the high-harmonic field of less than an attosecond (1 as = 10(-18) s) between
      the stretched and compressed geometry of weakly vibrationally excited Br(2) in
      the electronic ground state. The ability to probe structural and electronic
      features, combined with high time resolution, make high-harmonic spectroscopy
      ideally suited to measuring coupled electronic and nuclear dynamics occurring in
      photochemical reactions and to characterizing the electronic structure of
      transition states.

PMID- 20671707
TI  - Triggering of New Madrid seismicity by late-Pleistocene erosion.
AB  - The spatiotemporal behaviour of earthquakes within continental plate interiors is
      different from that at plate boundaries. At plate margins, tectonic motions
      quickly reload earthquake ruptures, making the location of recent earthquakes and
      the average time between them consistent with the faults' geological,
      palaeoseismic and seismic histories. In contrast, what determines the activation
      of a particular mid-continental fault and controls the duration of its seismic
      activity remains poorly understood. Here we argue that the concentration of
      magnitude-7 or larger earthquakes in the New Madrid seismic zone of the central
      United States since the end of the last ice age results from the recent, climate
      controlled, erosional history of the northern Mississippi embayment. We show that
      the upward flexure of the lithosphere caused by unloading from river incision
      between 16,000 and 10,000 years ago caused a reduction of normal stresses in the
      upper crust sufficient to unclamp pre-existing faults close to failure
      equilibrium. Models indicate that fault segments that have already ruptured are
      unlikely to fail again soon, but stress changes from sediment unloading and
      previous earthquakes may eventually be sufficient to bring to failure other
      nearby segments that have not yet ruptured.

PMID- 20671709
TI  - New class of gene-termini-associated human RNAs suggests a novel RNA copying
      mechanism.
AB  - Small (<200 nucleotide) RNA (sRNA) profiling of human cells using various
      technologies demonstrates unexpected complexity of sRNAs with hundreds of
      thousands of sRNA species present. Genetic and in vitro studies show that these
      RNAs are not merely degradation products of longer transcripts but could indeed
      have a function. Furthermore, profiling of RNAs, including the sRNAs, can reveal
      not only novel transcripts, but also make clear predictions about the existence
      and properties of novel biochemical pathways operating in a cell. For example,
      sRNA profiling in human cells indicated the existence of an unknown capping
      mechanism operating on cleaved RNA, a biochemical component of which was later
      identified. Here we show that human cells contain a novel type of sRNA that has
      non-genomically encoded 5' poly(U) tails. The presence of these RNAs at the
      termini of genes, specifically at the very 3' ends of known mRNAs, strongly
      argues for the presence of a yet uncharacterized endogenous biochemical pathway
      in cells that can copy RNA. We show that this pathway can operate on multiple
      genes, with specific enrichment towards transcript-encoding components of the
      translational machinery. Finally, we show that genes are also flanked by sense,
      3' polyadenylated sRNAs that are likely to be capped.

PMID- 20671708
TI  - Pathogenic LRRK2 negatively regulates microRNA-mediated translational repression.
AB  - Gain-of-function mutations in leucine-rich repeat kinase 2 (LRRK2) cause familial
      as well as sporadic Parkinson's disease characterized by age-dependent
      degeneration of dopaminergic neurons. The molecular mechanism of LRRK2 action is
      not known. Here we show that LRRK2 interacts with the microRNA (miRNA) pathway to
      regulate protein synthesis. Drosophila e2f1 and dp messenger RNAs are
      translationally repressed by let-7 and miR-184*, respectively. Pathogenic LRRK2
      antagonizes these miRNAs, leading to the overproduction of E2F1/DP, previously
      implicated in cell cycle and survival control and shown here to be critical for
      LRRK2 pathogenesis. Genetic deletion of let-7, antagomir-mediated blockage of let
      7 and miR-184* action, transgenic expression of dp target protector, or
      replacement of endogenous dp with a dp transgene non-responsive to let-7 each had
      toxic effects similar to those of pathogenic LRRK2. Conversely, increasing the
      level of let-7 or miR-184* attenuated pathogenic LRRK2 effects. LRRK2 associated
      with Drosophila Argonaute-1 (dAgo1) or human Argonaute-2 (hAgo2) of the RNA
      induced silencing complex (RISC). In aged fly brain, dAgo1 protein level was
      negatively regulated by LRRK2. Further, pathogenic LRRK2 promoted the association
      of phospho-4E-BP1 with hAgo2. Our results implicate deregulated synthesis of
      E2F1/DP caused by the miRNA pathway impairment as a key event in LRRK2
      pathogenesis and suggest novel miRNA-based therapeutic strategies.

PMID- 20671713
TI  - Hypernatremia and grade III/IV intraventricular hemorrhage among extremely low
      birth weight infants.
AB  - OBJECTIVE: To identify the risk factors contributing to intraventricular
      hemorrhage (IVH) in extremely low birth weight infants during early postnatal
      life, after appropriate matching for gestational age (GA) and birth body weight
      (BBW). STUDY DESIGN: A case-control retrospective study was designed to evaluate
      preterm infants with a GA <= 26 weeks and a BBW <= 1000 g admitted to our
      hospital during a 7.5-year period. From a cohort of 347 preterm infants, 36
      infants (10.7%) had severe IVH (grades III and/or IV). We selected a control
      group of 36 preterm infants without IVH who were closely matched for GA (+/- 1
      week) and body weight (+/- 100 g). Univariate and multivariate logistic
      regression analyses were performed to identify risk factors for severe IVH.
      RESULT: The GA and BBW of the IVH and control groups were 24.6 +/- 1 weeks and
      764.4 +/- 118.5 g, and 24.8 +/- 0.9 weeks and 771.5 +/- 125.9 g, respectively.
      Vaginal delivery, male sex, resuscitation in the delivery room, high sodium serum
      levels (meq l(-1)) (162.6 vs 148.8), fluctuation of serum sodium (meq l(-1))
      (17.3 vs 6.2), pH, PaCO(2), hemoglobin and platelet counts were associated with
      an increased risk of severe IVH. Multivariate logistic regression indicated that
      sodium fluctuations >13 meq l(-1), vaginal delivery, male sex and hemoglobin
      fluctuations are strongly associated with the development of severe IVH.
      CONCLUSION: Hypernatremia and fluctuations of sodium seem to be related to early
      severe IVH among preterm infants; however, further studies are required to
      clarify the causal relationship.

PMID- 20671714
TI  - Recombinant activated factor VIIa treatment for refractory hemorrhage in infants.
AB  - OBJECTIVE: Report clinical response to recombinant factor VIIa in a cohort of
      critically ill infants. STUDY DESIGN: We identified all infants who received
      factor VIIa in the Duke Neonatal Intensive Care Unit between January 2005 and
      July 2008. Hematological data and volume of blood transfusions before and after
      factor VIIa treatment were compared. The precipitating diagnosis for each factor
      VIIa use, and the ensuing clinical outcomes of bleeding, thrombosis and mortality
      were noted. RESULT: We identified 18 infants with median birth weight of 880 g
      and median gestational age of 26 weeks. One to six doses of factor VIIa (90 mcg
      kg(-1) per dose) were administered, with 13 (72%) infants receiving a single
      dose. Hemostasis was achieved in 13 (72%) of the infants. Prothrombin time and
      activated partial thromboplastin time significantly decreased following treatment
      with factor VIIa. Volume of plasma transfusions significantly decreased following
      treatment with factor VIIa (P=0.02). Thrombosis occurred in one (11%) infant. Six
      (33%) infants died within 72 h of treatment, and overall mortality was 10/18
      (56%). CONCLUSION: Treatment with factor VIIa at doses of 90 mcg kg(-1) improved
      coagulation studies and decreased the need for plasma transfusions in a group of
      critically ill infants without significant risk. Factor VIIa may be an effective
      addition to current treatment modalities for refractory hemorrhage in infants.

PMID- 20671715
TI  - Global notes: the interactions of health and foreign policies.

PMID- 20671716
TI  - Comparable effect of conventional ventilation versus early high-frequency
      oscillation on serum CC16 and IL-6 levels in preterm neonates.
AB  - OBJECTIVE: Clara cell 16 kD protein (CC16) and interleukin (IL)-6 have been used
      as peripheral blood biomarkers of alveolar leakage and inflammation,
      respectively. Thus, their measurement in the bloodstream could be used to assess
      ventilator-induced lung injury. The objective of this study was to evaluate the
      effect of optimized synchronized intermittent mandatory ventilation (SIMV) and
      high-frequency oscillatory ventilation (HFOV) on circulating CC16 and IL-6 levels
      when used as the initial ventilation modes in preterm neonates. STUDY DESIGN:
      Single center, prospective, randomized clinical study in preterm neonates
      (gestational age ?30 weeks) requiring mechanical ventilation within the first 2 h
      of life. Serum CC16 and IL-6 were measured on establishment of the assigned
      ventilation mode after admission, at days 3 and 14 of life as well as at 36 weeks
      postmenstrual age. Demographic-perinatal data and clinical parameters were also
      recorded. RESULT: Of the 30 neonates studied, 24 (gestational age 27.1+/-1.7
      weeks, birth weight 942+/-214 g) were finally analyzed, equally assigned into the
      SIMV and HFOV groups. Both groups had comparable demographic-perinatal
      characteristics and clinical parameters. Serum CC16 and IL-6 altered
      significantly over time (repeated-measures analysis of variance, both P<0.001).
      However, changes were not affected by the ventilation mode. Post hoc analysis
      showed a significant decrease in CC16 and IL-6 from birth up to 36 weeks
      postmenstrual age in both groups. CONCLUSION: In preterm neonates, SIMV and HFOV
      are associated with comparable circulating CC16 and IL-6 levels. These findings
      suggest a similar alveolar leakage and systemic inflammation with any of the
      ventilation modes evaluated when their usage is optimized.

PMID- 20671717
TI  - Systemic arterial pressure at maturity in rats following chronic hypoxia in early
      life.
AB  - BACKGROUND: The effect of prolonged hypoxemia in early life on systemic arterial
      blood pressure at maturity was assessed in Sprague-Dawley rats. METHODS: Animals
      hypoxic in early life (12 males, 10 females) were raised in hypoxia (FiO2 = 0.12)
      for the first 10 days of life and subsequently raised in normoxia, along with age
      matched controls (11 males, 9 females). At 2 months of age, arterial blood
      pressure was recorded intravascularly using telemetry in awake and unrestrained
      animals over two 12-h night-time (active) and daytime (resting) periods. Aortic
      pulse wave velocity was assessed in six additional hypoxic pretreated and five
      control anesthetized 2-month-old male rats. RESULTS: Systolic, mean, and pulse
      pressures were significantly greater in the hypoxic pretreated group compared to
      the control group during resting and active periods in both sexes (P <= 0.05).
      Diastolic pressure and heart rate did not differ between the two groups. Hypoxic
      pretreated males displayed significantly increased blood pressure variability
      during the resting period. Aortic pulse wave velocity was also found to be
      elevated in the hypoxic pretreated rats. CONCLUSIONS: Prolonged hypoxic stress in
      early life in the rat is associated with increased systolic arterial pressure at
      maturity very likely due to decreased arterial compliance. These findings suggest
      that a nutrient-independent, postnatal stress may lead to long-lasting vascular
      alterations predisposing to increased arterial pressure at maturity. This raises
      the possibility that adult survivors of congenital cyanotic cardiac disease may
      be at risk for secondary cardiovascular morbidity unrelated to surgical repair or
      residual cardiac defects.

PMID- 20671718
TI  - Reproducibility of masked hypertension in adults with untreated borderline office
      blood pressure: comparison of ambulatory and home monitoring.
AB  - BACKGROUND: We examined short-term reproducibility of masked hypertension (MH)
      among adults with recent "borderline" office blood pressure (BP) and compared
      agreement of ambulatory BP monitoring (ABPM) and home BP monitoring (HBPM) in
      detecting MH. METHODS: Fifty participants underwent repeated office BP
      measurements, 24-h ABPM, and HBPM sessions 1-week apart. Participants with office
      average <140/90 mm Hg were considered to have MH if daytime ABPM average was
      >=135/85 mm Hg; they were considered to have MH by HBPM if the average was
      >=135/85 mm Hg. Agreements were quantified using kappa. We calculated sensitivity
      and specificity of daytime ABPM-office average pairing and HBPM session-office
      average pairing for diagnosing MH using a "standard" of two pairings of office
      and 24-h average ABPM (using a cutoff >=130/80 mm Hg). RESULTS: Prevalence rates
      of MH based on office-daytime ABPM pairings were 54 and 53%, with agreement of
      73% (kappa = 0.47; 95% confidence interval (CI) 0.21-0.72). MH was less prevalent
      (43 and 35%) using HBPM-office pairings, with agreement of 69% (kappa = 0.34; 95%
      CI 0.06-0.62). Office-HBPM pairings and office-daytime ABPM pairings had poor
      agreement on MH classification on both occasions, with kappa of -0.06 and 0.10.
      Sensitivity and specificity of daytime ABPM-office pairing were 93 and 83%.
      Sensitivity and specificity of HBPM-office pairing were 23 and 67%. CONCLUSIONS:
      MH appears to have fair-to-moderate reproducibility, favoring the hypothesis that
      office BP measurement systematically fails to identify some patients who should
      be treated as hypertensive. HBPM may not be adequate for detecting MH, or may
      identify a different "type" of MH than ABPM.

PMID- 20671719
TI  - Association of target organ damage with three arterial stiffness indexes
      according to blood pressure dipping status in untreated hypertensive patients.
AB  - BACKGROUND: Subclinical organ damage represents an intermediate stage in the
      continuum of vascular disease and a determinant of overall cardiovascular risk.
      We investigated the associations of pulse wave velocity (PWV), ambulatory
      arterial stiffness index (AASI), and office pulse pressure (PP) with several
      target organ damages (TODs) in newly diagnosed and never-treated patients with
      essential hypertension with respect to their dipping profile. METHODS: One
      hundred sixty-eight hypertensive patients with recently diagnosed and never
      treated stage I-II essential hypertension were evaluated with respect to the
      relationship of PWV, AASI, and office PP with TOD including microalbumin (MAU)
      levels, cognitive function, intima-media thickness (IMT), coronary flow reserve
      (CFR), left ventricular mass (LVM), left ventricular filling pressures, diastolic
      dysfunction, and left atrium (LA) enlargement. RESULTS: Simultaneous estimation
      of AASI, PWV, and office PP independently associated with the following: (i) CFR
      (P < 0.01), 24-h urine albumin excretion rates (P < 0.05), left ventricular
      diastolic dysfunction (P < 0.01), and LA enlargement (P < 0.01) in never-treated
      hypertensive patients; (ii) CFR (P < 0.05), IMT (P < 0.01), left ventricular
      diastolic dysfunction (P < 0.05), and LA enlargement (P < 0.05) in dippers; and
      (iii) CFR (P < 0.05) and LA enlargement (P < 0.01) in nondippers. Nonindependent
      relationships revealed between (i) AASI and left ventricular filling pressures
      and (ii) PWV and cognitive dysfunction in never-treated hypertensive patients.
      CONCLUSIONS: The simultaneous estimation of three noninvasive indexes of arterial
      stiffness leads to valuable information regarding their association with TOD
      including CFR, MAU levels, IMT, left ventricular diastolic dysfunction, and LA
      enlargement in never-treated hypertensive patients regarding their dipping
      status.

PMID- 20671720
TI  - LASSBio-294, A compound with inotropic and lusitropic activity, decreases cardiac
      remodeling and improves Ca2(+) influx into sarcoplasmic reticulum after
      myocardial infarction.
AB  - BACKGROUND: Myocardial infarction (MI) is commonly associated with cardiac
      hypertrophy, reduced Ca2(+) uptake into the sarcoplasmic reticulum (SR) and
      impaired myocardial relaxation. Treatment to prevent MI-associated complications
      is currently lacking. The purpose of the present study was to investigate the
      remodeling and function of hearts subjected to experimental MI and to evaluate
      the response to treatment with a new thienylhydrazone: 3,4-methylenedioxybenzoyl
      2-thienylhydrazone (LASSBio-294), which has demonstrated positive inotropic
      properties. METHODS: LASSBio-294 (2 mg/kg) or vehicle (dimethyl sulfoxide) was
      administered daily by intraperitoneal injection for 4 weeks in sham-operated rats
      and rats with MI. Cardiac remodeling and hemodynamic parameters were monitored
      through histological and intraventricular pressure analyses. Intracellular Ca2(+)
      regulation (uptake and release) and the sensitivity of contractile proteins to
      Ca2(+) were evaluated by determining the contractile response of saponin-skinned
      cardiac cells from infarcted hearts. RESULTS: Cardiac hypertrophy occurred at 4
      weeks post-MI and was partially reverted by treatment with LASSBio-294. LASSBio
      294 treatment also reduced the nuclear density, collagen volume fraction, and
      left ventricular end-diastolic pressure (LV EDP) induced by MI. MI led to reduced
      Ca2(+) uptake from the SR, but did not modify the Ca2(+) release or the Ca2(+)
      force relationship. LASSBio-294 restored SR function and enhanced the sensitivity
      of contractile proteins to Ca2(+). CONCLUSION: LASSBio-294 is a promising
      candidate for improving intracellular Ca2(+) regulation and preventing MI-induced
      cardiac dysfunction, which could potentially prevent heart failure (HF).

PMID- 20671721
TI  - Resveratrol and small artery compliance and remodeling in the spontaneously
      hypertensive rat.
AB  - BACKGROUND: Small arteries from the spontaneously hypertensive rat (SHR) exhibit
      abnormal stiffness and geometry. This study investigated the effects of
      resveratrol, a polyphenol found in foods such as red grapes, on small arteries in
      SHR. METHODS: Wistar-Kyoto (WKY) rats and SHR were treated with resveratrol (2.5
      mg/kg/day) for 10 weeks. Mesenteric small artery segments (third-order branches)
      were mounted in a pressure myograph, and vascular geometry and mechanical
      properties were calculated from lumen and media dimensions measured at
      incremental intraluminal pressures. Systolic blood pressure was measured by tail
      cuff plethysmography. RESULTS: Increased compliance and reduced wall component
      stiffness were observed in SHR arteries vs. WKY arteries. Though resveratrol did
      not prevent lowering of wall component stiffness, it did attenuate, at least in
      part, the increased compliance of SHR arteries. In contrast, resveratrol
      increased compliance and reduced wall component stiffness in WKY arteries. SHR
      arteries exhibited remodeling that consisted of narrowed lumens, thickened media
      widths, and augmented media-to-lumen ratios. Resveratrol partially attenuated the
      remodeling process and also abolished exaggerated ERK signaling and expression of
      proliferating cell nuclear antigen (a marker of proliferation) in SHR arteries.
      The latter effects might be related to the ability of resveratrol to alleviate
      oxidative stress in SHR and enhance protein kinase G (PKG) activity. Elevated
      blood pressure in 20-week-old SHR was unaffected by resveratrol. CONCLUSIONS: The
      ability of resveratrol to limit the increase in compliance of SHR arteries is
      likely related to inhibitory effects on remodeling and pro-growth ERK signaling
      rather than blood pressure or arterial wall component stiffness.

PMID- 20671722
TI  - Genome-wide high-throughput integrome analyses by nrLAM-PCR and next-generation
      sequencing.
AB  - High-throughput integration site profiling has become a feasible tool to assess
      vector biosafety and to monitor the cell fate of the gene-corrected cell
      population in clinical gene therapy studies. Here we report a step-by-step
      protocol for universal genome-wide and comprehensive integrome analysis that can
      be performed on >10(2)-10(3) samples of interest in parallel. This assay is
      composed of fast and cost-efficient non-restrictive linear amplification-mediated
      PCR; optimized sample preparation for pyrosequencing; and automated bioinformatic
      data mining, including sequence trimming, alignment to the cellular genome and
      further annotation. Moreover, the workflow of this large-scale assay can be
      adapted to any PCR-based method aiming to characterize unknown flanking DNA
      adjacent to a known DNA region. Thus, in combination with next-generation
      sequencing technologies, large-scale integrome analysis of > 4 x 10(5)-1 x 10(6)
      integration site sequences can be accomplished within a single week.

PMID- 20671723
TI  - Monitoring apoptosis and neuronal degeneration by real-time detection of
      phosphatidylserine externalization using a polarity-sensitive indicator of
      viability and apoptosis.
AB  - Applications for noninvasive real-time imaging of apoptosis and neuronal
      degeneration are hindered by technical limitations in imaging strategies and by
      existing probes. Monitoring the progression of a cell through apoptosis could
      provide valuable insight into the temporal events that initiate cell death as
      well as the potential for rescue of apoptotic cells. We engineered an annexin
      based biosensor to function as a polarity-sensitive indicator for viability and
      apoptosis (known as pSIVA) by binding to externalized phosphatidylserine (PS)
      exposed on apoptotic cell membranes. Constructed from a structure-based design
      strategy, pSIVA fluoresces only when bound to PS and remains effectively
      undetectable in solution. In this paper, we describe protocols for the design,
      expression, purification and labeling of pSIVA as well as for its application in
      time-lapse imaging of degenerating neurons in culture; the entire protocol can be
      completed in 2 weeks. The primary advantage of this method is the flexibility to
      use pSIVA, in combination with other probes and without perturbing experimental
      conditions, to explore the cellular mechanisms involved in apoptosis and
      degeneration in real time.

PMID- 20671724
TI  - Intravital imaging of embryonic and tumor neovasculature using viral
      nanoparticles.
AB  - Viral nanoparticles are a novel class of biomolecular agents that take advantage
      of the natural circulatory and targeting properties of viruses to allow the
      development of therapeutics, vaccines and imaging tools. We have developed a
      multivalent nanoparticle platform based on the cowpea mosaic virus (CPMV) that
      facilitates particle labeling at high density with fluorescent dyes and other
      functional groups. Compared with other technologies, CPMV-based viral
      nanoparticles are particularly suited for long-term intravital vascular imaging
      because of their biocompatibility and retention in the endothelium with minimal
      side effects. The stable, long-term labeling of the endothelium allows the
      identification of vasculature undergoing active remodeling in real time. In this
      study, we describe the synthesis, purification and fluorescent labeling of CPMV
      nanoparticles, along with their use for imaging of vascular structure and for
      intravital vascular mapping in developmental and tumor angiogenesis models. Dye
      labeled viral nanoparticles can be synthesized and purified in a single day, and
      imaging studies can be conducted over hours, days or weeks, depending on the
      application.

PMID- 20671725
TI  - Derivation and characterization of haploid embryonic stem cell cultures in medaka
      fish.
AB  - Embryonic stem (ES) cells are pluripotent cells capable of differentiation into
      various cell types. Haploid ES cells elegantly combine the advantages of haploidy
      and pluripotency and offer a unique in vitro system for genetic analyses of
      molecular, cellular and developmental events in various cell lineages. Our recent
      success in generating haploid ES cell lines from gynogenetic embryos of the
      medaka fish suggests that haploidy can support ES cell derivation and maintenance
      in a vertebrate. In this study, we present a step-by-step protocol for derivation
      and characterization of medaka haploid ES cells. We have used this procedure to
      produce three haploid ES cell lines from five primary cultures. It takes about 15
      weeks to generate stable cultures, 5-8 weeks to obtain pure haploid cells and 5-6
      weeks to characterize ES cells in vitro and in vivo.

PMID- 20671726
TI  - High-throughput screening of tissue-nonspecific alkaline phosphatase for
      identification of effectors with diverse modes of action.
AB  - Here we describe a protocol for the identification of effectors of tissue
      nonspecific alkaline phosphatase (TNAP). It is based on a highly sensitive method
      for detecting TNAP activity. After dephosphorylation by TNAP, a dioxetane-based
      substrate undergoes a series of chemical transformations resulting in light
      production. Light intensity serves as a quantitative measure of the velocity of
      the TNAP-catalyzed reaction in the steady state. This protocol includes
      guidelines for optimizing the assay and for high-throughput screening in
      multiwell plates. The assay is sensitive to the influence of diverse effectors of
      TNAP as long as the assay optimization steps are repeated for each new batch of
      the enzyme; full optimization is accomplished in under 2 d. Depending on the
      available equipment, 10,000-100,000 compounds can be screened in an 8-h period.
      This protocol provides a method of screening TNAP that is 1,000-fold more
      sensitive and 10-fold faster than a conventional colorimetric assay with p
      nitrophenyl phosphate.

PMID- 20671727
TI  - Polymer-assisted deposition of homogeneous metal oxide films to produce nuclear
      targets.
AB  - Targets are essential in experimental nuclear sciences as a source of stationary
      nuclei for nuclear reactions with ion beams. Typically, targets should be
      chemically pure, uniform, homogeneous and crack-free over the irradiation area,
      while also being structurally rigid. The polymer-assisted deposition (PAD) method
      uses a water-soluble multidentate polymer that chelates metal precursors in
      solution. This polymer-metal solution is then spin coated and annealed to yield a
      crack-free, homogeneous metal oxide film. In this protocol, nuclear targets are
      created using PAD on silicon nitride (Si(3)N(4)) windows with silicon frames.
      Silicon wafers ([100], single-side polished) coated with 1 microm of silicon
      nitride on both sides are patterned and etched to create 1-microm silicon nitride
      windows. The PAD solution is then spun onto the silicon nitride window and
      annealed to create a thin, uniform metal oxide film of variable thickness on top
      of the silicon nitride backing. The production of a target window and the
      deposition of a thin film ranging from 50 to 150 nm takes approximately 13.5 h.
      Subsequent reapplications to grow thicker films require an additional 5 h per
      application.

PMID- 20671728
TI  - A bimolecular affinity purification method under denaturing conditions for rapid
      isolation of a ubiquitinated protein for mass spectrometry analysis.
AB  - Ubiquitination can have profound effects on the stability and function of
      cellular proteins. Mass spectrometry (MS) can be used to map the specific amino
      acid residues that are conjugated to ubiquitin in a target protein. However, the
      purification required for proteomic analysis can be challenging. In this paper,
      we describe a bimolecular affinity purification scheme for the isolation of a
      specific ubiquitinated protein in which affinity moieties are fused to ubiquitin
      and to a target protein of interest. After ubiquitin conjugation in vivo, the
      protein target acquires two affinity tags, allowing the specific purification of
      its ubiquitin-modified forms. To prevent deubiquitination after lysis or the
      copurification of interacting cofactors, this procedure is performed after
      protein denaturation using polyhistidine and biotinylation tags. Using this
      procedure, the ubiquitinated forms of a given protein can be efficiently purified
      in large amounts of sufficient purity for MS analysis and for mapping of
      ubiquitin acceptor sites.

PMID- 20671729
TI  - A 96-well-plate-based optical method for the quantitative and qualitative
      evaluation of Pseudomonas aeruginosa biofilm formation and its application to
      susceptibility testing.
AB  - A major reason for bacterial persistence during chronic infections is the
      survival of bacteria within biofilm structures, which protect cells from
      environmental stresses, host immune responses and antimicrobial therapy. Thus,
      there is concern that laboratory methods developed to measure the antibiotic
      susceptibility of planktonic bacteria may not be relevant to chronic biofilm
      infections, and it has been suggested that alternative methods should test
      antibiotic susceptibility within a biofilm. In this paper, we describe a fast and
      reliable protocol for using 96-well microtiter plates for the formation of
      Pseudomonas aeruginosa biofilms; the method is easily adaptable for antimicrobial
      susceptibility testing. This method is based on bacterial viability staining in
      combination with automated confocal laser scanning microscopy. The procedure
      simplifies qualitative and quantitative evaluation of biofilms and has proven to
      be effective for standardized determination of antibiotic efficiency on P.
      aeruginosa biofilms. The protocol can be performed within approximately 60 h.

PMID- 20671730
TI  - In vitro culture and expansion of human limbal epithelial cells.
AB  - Limbal stem cells (LSCs) have an important role in the maintenance of the corneal
      surface epithelium, and autologous cultured limbal epithelial cell
      transplantations have contributed substantially to the treatment of the visually
      disabling condition known as LSC deficiency. In this protocol, we describe a
      method of establishing human limbal epithelial cell cultures by a feeder-free
      explant culture technique using a small limbal biopsy specimen and human amniotic
      membrane (hAM) as the culture substrate. This protocol is free of animal-derived
      products and involves the use of human recombinant growth factors. In addition,
      the recombinant cell dissociation enzyme TrypLE is used to replace trypsin and
      autologous serum replaces FBS. It takes approximately 2 weeks to establish a
      confluent monolayer from which approximately 3 x 10(6) cells can be harvested.
      This procedure can be adopted for both basic research purposes and clinical
      applications.

PMID- 20671733
TI  - CD4+ T cells: a potential player in renal fibrosis.
AB  - T cells have a well-described role in renal injury, which leads to the secondary
      development of renal fibrosis. It has generally been assumed that this fibrotic
      response is an indirect consequence of T cell-mediated renal injury, rather than
      T cells' being directly involved in fibrosis. Tapmeier et al. now provide
      evidence that CD4(+) T cells promote interstitial fibrosis in the obstructed
      mouse kidney in a mechanism that appears to dissociate myofibroblast accumulation
      and matrix deposition.

PMID- 20671734
TI  - Therapeutic drug monitoring of mycophenolic acid: a potential treatment for lupus
      nephritis.
AB  - Mycophenolate mofetil, an immunosuppressant approved for the prevention of
      transplant rejection, has been used in patients with lupus nephritis.
      Lertdumrongluk et al. suggest that mycophenolic acid exposure may predict
      therapeutic responses in severe lupus nephritis, and their initial results
      confirm that hypothesis. However, it seems that enteric-coated mycophenolate
      sodium should not be administered to patients provided with therapeutic drug
      monitoring.

PMID- 20671735
TI  - Late perirenal fluid collection following ovarian hyperstimulation.

PMID- 20671736
TI  - Recurrent metabolic acidosis in a dialysis patient.

PMID- 20671737
TI  - Nucleotide supply, not local histone acetylation, sets replication origin usage
      in transcribed regions.
AB  - In eukaryotes, only a fraction of replication origins fire at each S phase. Local
      histone acetylation was proposed to control firing efficiency of origins, but
      conflicting results were obtained. We report that local histone acetylation does
      not reflect origin efficiencies along the adenosine monophosphate deaminase 2
      locus in mammalian fibroblasts. Reciprocally, modulation of origin efficiency
      does not affect acetylation. However, treatment with a deacetylase inhibitor
      changes the initiation pattern. We demonstrate that this treatment alters
      pyrimidine biosynthesis and decreases fork speed, which recruits latent origins.
      Our findings reconcile results that seemed inconsistent and reveal an unsuspected
      effect of deacetylase inhibitors on replication dynamics.

PMID- 20671738
TI  - Symposium proceedings. Perspective: irreversible progressive chronic kidney
      disease -- an overview.

PMID- 20671740
TI  - Stressful ethical issues in uremia therapy.
AB  - The objectives of this review are to introduce and explore the following
      representative ethical problems generated by modern renal replacement therapy:
      (1) reviewing the historical origin of medical ethics with specific reference to
      nephrology; (2) recognizing the complex stresses surrounding assignment of a
      deceased donor renal transplant to a geriatric patient while young patients
      continue waiting for a donor kidney; and (3) appreciating the concept of futility
      and support for a uremic patient opting for death rather than further uremia
      therapy as the best in choice in coping with renal failure.

PMID- 20671741
TI  - Anemia management in chronic kidney disease.
AB  - Anemia is one of the most common and morbid complications of chronic kidney
      disease, causing unpleasant symptoms and reducing the quality of life. The
      availability of recombinant human erythropoietin (rHuEPO) in 1989 has been one of
      the most important developments in the care of this population in the past
      several decades. Treatment with erythropoiesis-stimulating agents (ESAs) has
      improved patients' lives, but recent studies have found that higher hemoglobin
      (Hgb) targets cause harm, resulting in more cautious treatment. Despite
      widespread recognition by clinicians and patients of the value of this biological
      agent, the high cost and new concerns over safety have led to a reexamination of
      its use. Although rHuEPO is prescribed by individual physicians and target Hgb is
      guided by current evidence in the context of individual patients, critics within
      and outside the medical community have charged that rHuEPO is being overused,
      that financial motives are driving its use, and that patients are suffering from
      adverse consequences. Regulatory agencies, including the Centers for Medicare and
      Medicaid Services and the US Food and Drug Administration, have weighed in as
      well. In this review article, issues related to the current and future status of
      ESA treatment will be considered with a view to assessing factors that result in
      a lack of clarity and need for further study. It is essential that the renal
      community vigorously support additional rigorous research to expand the evidence
      base for optimal anemia management so that the debate over appropriate ESA use
      remains where it belongs, in the scientific domain.

PMID- 20671742
TI  - Treatment of secondary hyperparathyroidism in ESRD: a 2-year, single-center
      crossover study.
AB  - Secondary hyperparathyroidism (SHPT) is a common complication of chronic kidney
      disease. The management of SHPT commonly involves vitamin D, either calcitriol or
      newer analogs (paricalcitol or doxercalciferol), along with dietary phosphorus
      restriction and phosphate binding agents. Published reports have suggested that
      treatment with paricalcitol in hemodialyzed (HD) patients offers a morbidity or
      mortality advantage in comparison with treatment with calcitriol. We have
      recently reported that switching from calcitriol to paricalcitol resulted in a
      lower serum calcium and calcium-phosphorus product (Ca x P product), as well as
      lower parathyroid hormone (PTH) and alkaline phosphatase during 6 months of
      serial treatment. We converted all HD patients in our large urban dialysis center
      from calcitriol to paricalcitol using a 1:3 conversion ratio, on the basis of
      published data. Comparisons of individual patient mean biochemical values, as
      well as episodes of hypercalcemia and elevated Ca x P product, were made after
      adjusting for equivalent doses. In addition, we recorded the number of missed
      doses during two years of therapy. No patient in this study had received a
      calcimimetic before or during the study period. Fifty-nine patients were treated
      with calcitriol for at least 12 months and then completed 12 months of
      paricalcitol. Conversion from calcitriol to paricalcitol resulted in lower serum
      calcium (P=0.0003), lower serum phosphorus (P=0.027), lower Ca x P product
      (P=0.003), reduced PTH (P=0.001) and reduced serum alkaline phosphatase
      (P=0.0005). Most dramatically, there was a highly significant difference in the
      number of missed doses (P<0.0001) during the treatments. This 2-year single
      center study, comparing long-term calcitriol with paricalcitol treatment in the
      same HD patients, extends our previous findings, offers new information regarding
      single episodes of potentially adverse biochemical effects related to vitamin D
      therapy, and provides several clues that may explain the outcome advantages
      suggested by previously published retrospective analyses of large dialysis
      provider-pooled databases.

PMID- 20671739
TI  - Kidney bone disease and mortality in CKD: revisiting the role of vitamin D,
      calcimimetics, alkaline phosphatase, and minerals.
AB  - Recent evidence suggests that the traditional syndromes known as renal
      osteodystrophy, secondary hyperparathyroidism, and vitamin D deficiency are
      related to mortality in persons with moderate to advanced chronic kidney disease
      (CKD). The so-called 'kidney bone disease', also known as 'mineral and bone
      disorders', is defined to include bone disorders, mineral disarrays, and vascular
      calcification. We have identified 14 common and clinically relevant conditions of
      contemporary nature that are related to the kidney bone disease, including
      calcitriol (active vitamin D) deficiency, 25(OH)-vitamin D deficiency,
      biochemical hyperparathyroidism, relatively low parathyroid hormone (PTH) level,
      increased serum alkaline phosphatase (hyperphosphatasemia), elevated fibroblast
      growth factor (FGF)-23, high turnover bone disease, adynamic bone disease, uremic
      osteoporosis, vascular calcification, hyper- and hypophosphatemia, and hyper- and
      hypocalcemia. We present a critical review of these 14 conditions with emphasis
      on patient survival and other pertinent clinical outcomes. We also review
      unresolved controversies surrounding the management of these conditions by
      administration of nutritional vitamin D (ergocalciferol and cholecalciferol),
      vitamin D receptor activators (calcitriol, alphacalcidiol, doxercalciferol), D
      mimetics (paricalcitol, maxacalcitol), calcimimetics (cinacalcet), recombinant
      PTH (teriparatide), and receptor activator of nuclear factor-kappaB ligand
      modulators (denosumab); compare mortality predictability of PTH and alkaline
      phosphatase; and examine potential risks of bone disorders and mineral disarrays
      in CKD patients.

PMID- 20671743
TI  - Extracellular mass/body cell mass ratio is an independent predictor of survival
      in peritoneal dialysis patients.
AB  - Malnutrition is a strong predictor of mortality in peritoneal dialysis (PD)
      patients. Extracellular mass (ECM) contains all the metabolically inactive,
      whereas body cell mass (BCM) contains all the metabolically active, tissues of
      the body. ECM/BCM ratio is a highly sensitive index of malnutrition. The
      objective of this study was to explore the relationship between ECM/BCM ratio and
      survival in PD patients. We enrolled 62 patients from November 2000 to July 2008.
      On enrollment, demographic, clinical, and biochemical data were recorded.
      Bioimpedance analysis (BIA) was used to determine ECM and BCM in PD patients.
      Patients were followed up to November 2008. Mean age was 54+/-16 (s.d.) years;
      female, 55%; African Americans, 65%; diabetic, 24%. Mean ECM/BCM ratio was
      1.206+/-0.197 (range: 0.73-1.62). Diabetics had higher ECM/BCM ratio than
      nondiabetics (1.29 vs 1.18, P=0.04). ECM/BCM ratio correlated directly with age
      (r=0.38, P=0.002) and inversely with serum albumin (r=-0.43, P=0.001), creatinine
      (-0.24, P=0.08), blood urea nitrogen (r=-0.26, P=0.06), and total protein (r=
      0.31, P=0.026). Using multivariate Cox regression analysis, adjusting for age,
      race, gender, diabetes, and human immunodeficiency virus status, enrollment
      ECM/BCM ratio was a significant independent predictor of mortality (relative
      risk=1.035, P=0.018). For every 10% increase in the ECM/BCM ratio, the relative
      risk of death was increased by about 35%. In conclusion, BIA-derived enrollment
      ECM/BCM ratio, a marker of malnutrition, was an independent predictor of long
      term survival in PD patients.

PMID- 20671744
TI  - Serum fructosamine versus glycosylated hemoglobin as an index of glycemic
      control, hospitalization, and infection in diabetic hemodialysis patients.
AB  - Diabetes is the most common cause of end-stage renal disease and an important
      risk factor for morbidity and mortality in dialysis patients. Glycemic control,
      utilizing serial measurement of glycosylated hemoglobin (HbA1c), is generally
      recommended to limit end-organ damage, including cardiovascular morbidity and
      mortality. We, along with others, have previously suggested that HbA1c may not be
      a reliable measure of glycemic control in dialysis patients, and have therefore
      explored the use of serum fructosamine (SF) as an alternative marker. The
      objective of this study was to compare HbA1c levels with SF in monitoring
      glycemic control and associated morbidity (infection and hospitalization) in
      diabetic patients in a large urban hemodialysis (HD) center. We enrolled 100
      diabetic HD patients and followed them up prospectively for 3 years. Data on
      demographics, as well as biochemical and clinical data, including
      hospitalizations and infections, were recorded. The mean age was 63 years. In all
      54% were women and the majority were African Americans (72%). As expected, HbA1c
      and albumin-corrected fructosamine (AlbF) levels were highly correlated and both
      were significantly associated with serum glucose. AlbF, however, was more highly
      correlated with mean glucose values when less than 150 mg/dl and was a more
      useful predictor of morbidity. By univariate logistic regression and by Poisson
      regression analysis, AlbF, but not HbA1c, was a significant predictor of
      hospitalization. Additionally, in patients dialyzed by arteriovenous (AV) access
      (that is, excluding those dialyzed via vascular catheters), AlbF, but not HbA1c,
      was a significant predictor of infection. In conclusion, AlbF is as reliable a
      marker as HbA1c for glycemic control in diabetic patients on HD, and may be
      advantageous for patients with serum glucose in a desirable therapeutic range
      (<150 mg/dl). In addition, AlbF, but not HbA1c, is associated with morbidity
      (hospitalizations and infections) in diabetic patients on HD.

PMID- 20671745
TI  - Glucocorticoid-induced activation of caspase-8 protects the glucocorticoid
      induced protein Gilz from proteasomal degradation and induces its binding to SUMO
      1 in murine thymocytes.
AB  - In this study, we evaluated the possible cross-talk between glucocorticoid (GC)
      induced leucine zipper (Gilz) and caspase-8 in dexamethasone (Dex)-treated
      thymocytes. We determined that expression of Dex-induced Gilz protein was reduced
      when caspase-8 activity was inhibited, and this effect was not partially due to
      altered Gilz mRNA expression. Inhibition of the proteasome abrogated this
      reduction in Gilz expression, suggesting that Dex-induced caspase-8 activation
      protects Gilz from degradation. We hypothesized that the caspase-8-dependent
      protection of Gilz could be due to caspase-8-driven sumoylation. As a putative
      small ubiquitin-like modifier (SUMO)-binding site was identified in the Gilz
      sequence, we assessed whether SUMO-1 interacted with Gilz. We identified a 30-kDa
      protein that was compatible with the size of a Gilz-SUMO-1 complex and was
      recognized by the anti-SUMO-1 and anti-Gilz antibodies. In addition, Gilz bound
      to SUMO ubiquitin-conjugating (E2)-conjugating enzyme Ube21 (Ubc9), the specific
      SUMO-1 E2-conjugating enzyme, in vitro and coimmunoprecipitated with Ubc9 in
      vivo. Furthermore, Gilz coimmunoprecipitated with SUMO-1 both in vitro and in
      vivo, and this interaction depended on caspase-8 activation. This requirement for
      caspase-8 was further evaluated in caspase-8-deficient thymocytes and lymphocytes
      in which Gilz expression was reduced. In summary, our results suggest that
      caspase-8 activation protects Gilz from proteasomal degradation and induces its
      binding to SUMO-1 in GC-treated thymocytes.

PMID- 20671746
TI  - Very low oxygen concentration (0.1%) reveals two FDCP-Mix cell subpopulations
      that differ by their cell cycling, differentiation and p27KIP1 expression.
AB  - Oxygen (O(2)) concentrations in bone marrow vary from 4% in capillaries to <0.1%
      in subendosteum, in which hematopoietic stem cells reside in specific niches.
      Culture at low O(2) concentrations (3, 1 and 0.1%) influences hematopoietic stem
      and progenitor cells survival, proliferation and differentiation, depending on
      their level of differentiation. Culture of human CD34(+) cells at low O(2)
      concentrations (O(2) <=3%) maintains stem cell engraftment potential better than
      at 20% O(2) (NOD/Scid xenograft model). In contrast, progenitors disappear from
      cultures at/or <1% O(2) concentrations. A very low O(2) concentration (0.1%)
      induces CD34(+) quiescence in G(0). The exploration of molecules and mechanisms
      involved in hematopoietic stem and progenitor cells' quiescence and
      differentiation related to low O(2) concentrations is unfeasible with primary
      CD34(+) cells. Therefore, we performed it using murine hematopoietic nonleukemic
      factor-dependent cell Paterson (FDCP)-Mix progenitor cell line. The culture of
      the FDCP-Mix line at 0.1% O(2) induced in parallel G(0) quiescence and granulo
      monocytic differentiation of most cells, whereas a minority of undifferentiated
      self-renewing cells remained in active cell cycle. Hypoxia also induced
      hypophosphorylation of pRb and increased the expression of p27(KIP1), the two
      proteins that have a major role in the control of G(0) and G(1) to S-phase
      transition.

PMID- 20671747
TI  - Maximal adamantyl-substituted retinoid-related molecule-induced apoptosis
      requires NF-kappaB noncanonical and canonical pathway activation.
AB  - NF-kappaB transcription factors have a critical role in regulating cell survival
      and apoptosis. We have previously shown that 4-(3-Cl-(1-adamantyl)-4
      hydroxyphenyl)-3-chlorocinnamic acid (3-Cl-AHPC), an adamantyl-substituted
      retinoid molecule, induced apoptosis and required NF-kappaB activation in
      prostate and breast carcinoma cells. Here, we show that 3-Cl-AHPC activated both
      IkappaB kinase (IKK)alpha and IKKbeta with subsequent activation of the canonical
      and noncanonical NF-kappaB pathways in the human breast carcinoma and leukemia
      cell lines. 3-Cl-AHPC-mediated activation of the NF-kappaB canonical pathway
      occurred within 6 h, whereas maximal activation of the NF-kappaB noncanonical
      pathway required 48 h. Knockout of IKKalpha or IKKbeta expression in mouse
      embryonic fibroblast cells and knockdown of IKKalpha or IKKbeta in MDA-MB-468
      cells resulted in the inhibition of 3-Cl-AHPC-mediated apoptosis, indicating that
      activation of canonical and noncanonical pathways are required for maximal 3-Cl
      AHPC-mediated apoptosis. 3-Cl-AHPC activation of the noncanonical pathway was
      preceded by caspase-mediated decrease in the E3-ligase c-IAP1 with subsequent
      stabilization of NF-kappaB-inducing kinase (NIK) expression, increased binding of
      NIK by TRAF3, activation of IKKalpha, and the resultant increased levels of RelB
      and p52. Increased expression of c-IAP1 blocked 3-Cl-AHPC-mediated stabilization
      of NIK levels and 3-Cl-AHPC-mediated apoptosis. Cdc37 expression was required for
      activation of IKKalpha and IKKbeta by 3-Cl-AHPC. These findings suggest that NF
      kappaB pathways have an important role in 3-Cl-AHPC-mediated apoptosis.

PMID- 20671748
TI  - Bcl-2 family interaction with the mitochondrial morphogenesis machinery.
AB  - The regulation of both mitochondrial dynamics and apoptosis is key for
      maintaining the health of a cell. Bcl-2 family proteins, central in apoptosis
      regulation, also have roles in the maintenance of the mitochondrial network. Here
      we report that Bax and Bak participate in the regulation of mitochondrial fusion
      in mouse embryonic fibroblasts, primary mouse neurons and human colon carcinoma
      cells. To assess how Bcl-2 family members may regulate mitochondrial
      morphogenesis, we determined the binding of a series of chimeras between Bcl-xL
      and Bax to the mitofusins, mitofusin 1 (Mfn1) and mitofusin 2 (Mfn2). One chimera
      (containing helix 5 (H5) of Bax replacing H5 of Bcl-xL (Bcl-xL/Bax H5)) co
      immunoprecipitated with Mfn1 and Mfn2 significantly better than either wild-type
      Bax or Bcl-xL. Expression of Bcl-xL/Bax H5 in cells reduced the mobility of Mfn1
      and Mfn2 and colocalized with ectopic Mfn1 and Mfn2, as well as endogenous Mfn2
      to a greater extent than wild-type Bax. Ultimately, Bcl-xL/Bax H5 induced
      substantial mitochondrial fragmentation in healthy cells. Therefore, we propose
      that Bcl-xL/Bax H5 disturbs mitochondrial morphology by binding and inhibiting
      Mfn1 and Mfn2 activity, supporting the hypothesis that Bcl-2 family members have
      the capacity to regulate mitochondrial morphology through binding to the
      mitofusins in healthy cells.

PMID- 20671750
TI  - Hope builds for earlier detection of Alzheimer's disease.

PMID- 20671749
TI  - Serine 312 phosphorylation is dispensable for wild-type p53 functions in vivo.
AB  - Cellular stimulation results in phosphorylation of the tumor suppressor p53 on
      multiple residues, though the functional relevance is not always clear. It is
      noteworthy that the serine (S) 315 residue is unique, as it has been suggested to
      be phosphorylated not only by genotoxic signals, but also during cell-cycle
      progression and by endoplasmic-reticulum stress. However, in vitro data have been
      conflicting as phosphorylation at this site was shown to both positively and
      negatively regulate p53 functions. We have thus generated knock-in mice
      expressing an unphosphorylable S312 (equivalent to human S315), by substitution
      with an alanine (A) residue, to clarify the conflicting observations and to
      evaluate its functional relevance in vivo. Born at Mendelian ratios, the
      p53(S312A/S312A) mice show no anomalies during development and adulthood. p53
      activation, stability, localization and ability to induce apoptosis, cell-cycle
      arrest and prevent centrosome amplification are not compromised in
      p53(S312A/S312A) cells. p53(S312A/S312A) mice are unable to rescue mdm2(-/-)
      lethality, and tumorigenesis--both spontaneous and irradiation/oncogene-induced-
      is not accentuated. Taken together, the results show that the S312
      phosphorylation site is not in itself necessary for efficient p53 function, and
      advocates the possibility that it is neither relevant in the mouse context nor
      important for p53 functions in vivo.

PMID- 20671751
TI  - China spurs pharma innovation.

PMID- 20671753
TI  - Deal watch: Abbott and Neurocrine to develop promising endometriosis drug.

PMID- 20671754
TI  - Trial watch: ipilimumab success in melanoma provides boost for cancer
      immunotherapy.

PMID- 20671755
TI  - Regulatory watch: impact of PDUFA on regulatory decision-making.

PMID- 20671757
TI  - Jean-Jacques Garaud. Interview by Bethan Hughes.

PMID- 20671758
TI  - Denosumab.

PMID- 20671759
TI  - Lead identification: combining strengths to find high-quality leads.

PMID- 20671760
TI  - Cancer: steps towards a prophylactic breast cancer vaccine.

PMID- 20671761
TI  - Inflammation: the fat controller.

PMID- 20671762
TI  - Genetic diseases: new tricks for known drugs.

PMID- 20671763
TI  - Spinal cord injury: the two faces of spontaneous serotonin signalling.

PMID- 20671766
TI  - Gene and drug matrix for personalized cancer therapy.

PMID- 20671767
TI  - Nonarteritic anterior ischaemic optic neuropathy in Addison's disease.
AB  - PURPOSE: To report three cases of Nonarteritic anterior ischaemic optic
      neuropathy (NAAION) in patients with Addison's disease. METHODS: We present a
      retrospective review of patients presenting with NAAION with underlying Addison's
      disease. RESULTS: Three eyes of two young patients presented with NAAION. Both
      patients had underlying Addison's disease with episodes of prolonged hypotension.
      CONCLUSION: To our knowledge, this is the first published report of NAAION
      associated with Addison's disease. As hypotension may be one of the few
      situations, in which NAAION may be treatable and the visual loss reversible, it
      is important to recognize and treat sustained episodes of hypotension in these
      individuals.

PMID- 20671764
TI  - Coexistence of passive and carrier-mediated processes in drug transport.
AB  - The permeability of biological membranes is one of the most important
      determinants of the pharmacokinetic processes of a drug. Although it is often
      accepted that many drug substances are transported across biological membranes by
      passive transcellular diffusion, a recent hypothesis speculated that carrier
      mediated mechanisms might account for the majority of membrane drug transport
      processes in biological systems. Based on evidence of the physicochemical
      characteristics and of in vitro and in vivo findings for marketed drugs, as well
      as results from real-life discovery and development projects, we present the view
      that both passive transcellular processes and carrier-mediated processes coexist
      and contribute to drug transport activities across biological membranes.

PMID- 20671768
TI  - Spontaneous hyphaema and acute ocular hypertension associated with severe lens
      induced uveitis.
AB  - PURPOSE: to report the occurrence of spontaneous hyphaema and acute ocular
      hypertension in four patients with severe lens-induced anterior uveitis. METHODS:
      retrospective case series. RESULTS: four patients with mature cataract developed
      severe acute, unilateral, anterior uveitis associated with spontaneous hyphaema
      formation and acutely elevated intraocular pressure. None of the patients had a
      history of trauma or evidence of angle, iris, or retinal neovascularization.
      Prompt cataract removal led to resolution of the inflammation, clearing of the
      anterior chamber haemorrhage, and normalization of intraocular pressure in all
      four affected eyes. CONCLUSIONS: spontaneous hyphaema and acute ocular
      hypertension can occur in patients with severe lens-induced intraocular
      inflammation in the absence of trauma or ocular neovascularization.

PMID- 20671765
TI  - Multifaceted polo-like kinases: drug targets and antitargets for cancer therapy.
AB  - The polo-like kinase 1 (PLK1) acts in concert with cyclin-dependent kinase 1
      cyclin B1 and Aurora kinases to orchestrate a wide range of critical cell cycle
      events. Because PLK1 has been preclinically validated as a cancer target, small
      molecule inhibitors of PLK1 have become attractive candidates for anticancer drug
      development. Although the roles of the closely related PLK2, PLK3 and PLK4 in
      cancer are less well understood, there is evidence showing that PLK2 and PLK3 act
      as tumour suppressors through their functions in the p53 signalling network,
      which guards the cell against various stress signals. In this article, recent
      insights into the biology of PLKs will be reviewed, with an emphasis on their
      role in malignant transformation, and progress in the development of small
      molecule PLK1 inhibitors will be examined.

PMID- 20671769
TI  - Osteosarcoma cells as carriers to allow antitumor activity of canine oncolytic
      adenovirus in the presence of neutralizing antibodies.
AB  - Osteosarcoma (OSA) is the most common bone tumor affecting the dog. The
      veterinary options for therapeutic management of OSA are limited and prognosis
      for such patients is poor. Oncolytic adenoviruses are attractive tools for
      experimental therapeutics as they can replicate and spread within tumors to
      directly induce tumor destruction. However, a major impediment to systemic
      oncolytic adenoviruses injection is the presence of pre-existing neutralizing
      antibodies (Nabs). In this study, we investigated the effect of a replication
      selective canine adenovirus (OCCAV) to treat OSA in the presence of Nabs and the
      use of canine OSA cells as carrier vehicles for evading Nabs. Our systemic
      biodistribution data indicated that canine tumor cells could successfully reach
      the tumor site and deliver OCCAV to tumor cells in an immunized mice model.
      Furthermore, the use of carrier cells also reduced adenovirus uptake by the
      liver. Importantly, OCCAV alone was not effective to control tumor growth in a
      pre-immunized xenograft mouse model. On the contrary, systemic antitumoral
      activity of carrier-cell OCCAV was evident even in the presence of circulating
      antibodies, which is a relevant result from a clinical point of view. These
      findings are of direct translational relevance for the future design of canine
      clinical trials.

PMID- 20671771
TI  - eCAM: Attacking an Epidemic?

PMID- 20671770
TI  - Mao-to Prolongs the Survival of and Reduces TNF-alpha Expression in Mice with
      Viral Myocarditis.
AB  - Goal of this study was to evaluate effects of Mao-to on development of
      myocarditis induced by encephalomyocarditis (EMC) virus in mice. Mice were
      randomly divided into five groups. Group N included uninfected controls (n = 18),
      while group A, B and C underwent intraperitoneal injection of EMC virus. Group A
      was administered oral saline from day 0 to day 4. Group B was administered oral
      Mao-to (500 mg(-1) kg(-1) day(-1)) from day 0 to day 4. Group C was administered
      Mao-to from day 2 to day 6. Group D was administered Mao-to from day 5 to day 10.
      Treated mice were followed for survival rates during 2 weeks after infection.
      Body weight (BW) and organ weights including heart (HW), lungs, thymus and spleen
      were examined on days 4, 6 and 14. Survival rate of group C (36.4%) was
      significantly improved compared with group A, B or D (0% of each, P < 0.05). HW
      and HW/BW ratio in group C was significantly (P < 0.05) lower than those in group
      A, B or D. Viral titers of hearts were significantly different among groups A, B
      and C. Cardiac expression in tumor necrosis factor-alpha (TNF-alpha) was
      significantly reduced in group C in comparison with group A, B or D on day 6 by
      immunohistochemical study. Administration of Mao-to starting on day 2 improves
      mortality resulting from viral myocarditis in mice with reduced expression of
      cardiac TNF-alpha. These findings suggest that timing of Mao-to is crucial for
      preventing cardiac damage in mice with viral myocarditis.

PMID- 20671772
TI  - Conserved Daily Transcriptional Programs in Carica papaya.
AB  - Most organisms have internal circadian clocks that mediate responses to daily
      environmental changes in order to synchronize biological functions to the correct
      times of the day. Previous studies have focused on plants found in temperate and
      sub-tropical climates, and little is known about the circadian transcriptional
      networks of plants that typically grow under conditions with relatively constant
      day lengths and temperatures over the year. In this study we conducted a genomic
      and computational analysis of the circadian biology of Carica papaya, a tropical
      tree. We found that predicted papaya circadian clock genes cycle with the same
      phase as Arabidopsis genes. The patterns of time-of-day overrepresentation of
      circadian-associated promoter elements were nearly identical across papaya,
      Arabidopsis, rice, and poplar. Evolution of promoter structure predicts the
      observed morning- and evening-specific expression profiles of the papaya PRR5
      paralogs. The strong conservation of previously identified circadian
      transcriptional networks in papaya, despite its tropical habitat and distinct
      life-style, suggest that circadian timing has played a major role in the
      evolution of plant genomes, consistent with the selective pressure of
      anticipating daily environmental changes. Further studies could exploit this
      conservation to elucidate general design principles that will facilitate
      engineering plant growth pathways for specific environments. ELECTRONIC
      SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12042
      008-9020-3) contains supplementary material, which is available to authorized
      users.

PMID- 20671773
TI  - eCAM: Retaining an International Perspective.

PMID- 20671774
TI  - Grafted block complex coacervate core micelles and their effect on protein
      adsorption on silica and polystyrene.
AB  - We have studied the formation and the stability of grafted block complex
      coacervate core micelles (C3Ms) in solution and the influence of grafted block
      C3M coatings on the adsorption of the proteins beta-lactoglobulin, bovine serum
      albumin, and lysozyme. The C3Ms consist of a grafted block copolymer PAA(21)-b
      PAPEO(14) (poly(acrylic acid)-b-poly(acrylate methoxy poly(ethylene oxide)), with
      a negatively charged PAA block and a neutral PAPEO block and a positively charged
      homopolymer P2MVPI (poly(N-methyl 2-vinyl pyridinium iodide). In solution, these
      C3Ms partly disintegrate at salt concentrations between 50 and 100 mM NaCl.
      Adsorption of C3Ms and proteins has been studied with fixed-angle optical
      reflectometry, at salt concentrations ranging from 1 to 100 mM NaCl. In
      comparison with the adsorption of PAA(21)-b-PAPEO(14) alone adsorption of C3Ms
      significantly increases the amount of PAA(21)-b-PAPEO(14) on the surface. This
      results in a higher surface density of PEO chains. The stability of the C3M
      coatings and their influence on protein adsorption are determined by the
      composition and the stability of the C3Ms in solution. A C3M-PAPEO(14)/P2MVPI(43)
      coating strongly suppresses the adsorption of all proteins on silica and
      polystyrene. The reduction of protein adsorption is the highest at 100 mM NaCl
      (>90%). The adsorbed C3M-PAPEO(14)/P2MVPI(43) layer is partly removed from the
      surface upon exposure to an excess of beta-lactoglobulin solution, due to
      formation of soluble aggregates consisting of beta-lactoglobulin and P2MVPI(43).
      In contrast, C3M-PAPEO(14)/P2MVPI(228) which has a fivefold longer cationic block
      enhances adsorption of the negatively charged proteins on both surfaces at salt
      concentrations above 1 mM NaCl. A single PAA(21)-b-PAPEO(14) layer causes only a
      moderate reduction of protein adsorption.

PMID- 20671775
TI  - Vacancy-mediated magnetism in pure copper oxide nanoparticles.
AB  - Room temperature ferromagnetism (RTF) is observed in pure copper oxide (CuO)
      nanoparticles which were prepared by precipitation method with the post-annealing
      in air without any ferromagnetic dopant. X-ray photoelectron spectroscopy (XPS)
      result indicates that the mixture valence states of Cu1+ and Cu2+ ions exist at
      the surface of the particles. Vacuum annealing enhances the ferromagnetism (FM)
      of CuO nanoparticles, while oxygen atmosphere annealing reduces it. The origin of
      FM is suggested to the oxygen vacancies at the surface/or interface of the
      particles. Such a ferromagnet without the presence of any transition metal could
      be a very good option for a class of spintronics.

PMID- 20671776
TI  - Finite-Element Modelling of Biotransistors.
AB  - Current research efforts in biosensor design attempt to integrate biochemical
      assays with semiconductor substrates and microfluidic assemblies to realize fully
      integrated lab-on-chip devices. The DNA biotransistor (BioFET) is an example of
      such a device. The process of chemical modification of the FET and attachment of
      linker and probe molecules is a statistical process that can result in variations
      in the sensed signal between different BioFET cells in an array. In order to
      quantify these and other variations and assess their importance in the design,
      complete physical simulation of the device is necessary. Here, we perform a mean
      field finite-element modelling of a short channel, two-dimensional BioFET device.
      We compare the results of this model with one-dimensional calculation results to
      show important differences, illustrating the importance of the molecular
      structure, placement and conformation of DNA in determining the output signal.

PMID- 20671777
TI  - Noninjection Synthesis of CdS and Alloyed CdSxSe1-xNanocrystals Without
      Nucleation Initiators.
AB  - CdS and alloyed CdSxSe1-x nanocrystals were prepared by a simple noninjection
      method without nucleation initiators. Oleic acid (OA) was used to stabilize the
      growth of the CdS nanocrystals. The size of the CdS nanocrystals can be tuned by
      changing the OA/Cd molar ratios. On the basis of the successful synthesis of CdS
      nanocrystals, alloyed CdSxSe1-x nanocrystals can also be prepared by simply
      replacing certain amount of S precursor with equal amount of Se precursor,
      verified by TEM, XRD, EDX as well as UV-Vis absorption analysis. The optical
      properties of the alloyed CdSxSe1-x nanocrystals can be tuned by adjusting the
      S/Se feed molar ratios. This synthetic approach developed is highly reproducible
      and can be readily scaled up for potential industrial production.

PMID- 20671778
TI  - The Photodynamic Effect of Different Size ZnO Nanoparticles on Cancer Cell
      Proliferation In Vitro.
AB  - Nanomaterials have widely been used in the field of biological and biomedicine,
      such as tissue imaging, diagnosis and cancer therapy. In this study, we explored
      the cytotoxicity and photodynamic effect of different-sized ZnO nanoparticles to
      target cells. Our observations demonstrated that ZnO nanoparticles exerted dose
      dependent and time-dependent cytotoxicity for cancer cells like hepatocellular
      carcinoma SMMC-7721 cells in vitro. Meanwhile, it was observed that UV
      irradiation could enhance the suppression ability of ZnO nanoparticles on cancer
      cells proliferation, and these effects were in the size-dependent manner.
      Furthermore, when ZnO nanoparticles combined with daunorubicin, the related
      cytotoxicity of anticancer agents on cancer cells was evidently enhanced,
      suggesting that ZnO nanoparticles could play an important role in drug delivery.
      This may offer the possibility of the great potential and promising applications
      of the ZnO nanoparticles in clinical and biomedical areas like photodynamic
      cancer therapy and others.

PMID- 20671779
TI  - Self Assembly and Properties of C:WO(3) Nano-Platelets and C:VO(2)/V(2)O(5)
      Triangular Capsules Produced by Laser Solution Photolysis.
AB  - Laser photolysis of WCl(6) in ethanol and a specific mixture of V(2)O(5) and
      VCl(3) in ethanol lead to carbon modified vanadium and tungsten oxides with
      interesting properties. The presence of graphene's aromatic rings (from the
      vibrational frequency of 1,600 cm(-1)) together with C-C bonding of carbon (from
      the Raman shift of 1,124 cm(-1)) present unique optical, vibrational, electronic
      and structural properties of the intended tungsten trioxide and vanadium dioxide
      materials. The morphology of these samples shows nano-platelets in WO(x) samples
      and, in VO(x) samples, encapsulated spherical quantum dots in conjunction with
      fullerenes of VO(x). Conductivity studies revealed that the VO(2)/V(2)O(5)
      nanostructures are more sensitive to Cl than to the presence of ethanol, whereas
      the C:WO(3) nano-platelets are more sensitive to ethanol than atomic C.

PMID- 20671780
TI  - Synthesis and Photocatalytic Activity of Anatase TiO2 Nanoparticles-coated Carbon
      Nanotubes.
AB  - A simple and straightforward approach to prepare TiO2-coated carbon nanotubes
      (CNTs) is presented. Anatase TiO2 nanoparticles (NPs) with the average size ~8 nm
      were coated on CNTs from peroxo titanic acid (PTA) precursor even at low
      temperature of 100  degrees C. We demonstrate the effects of CNTs/TiO2 molar
      ratio on the adsorption capability and photocatalytic efficiency under UV-visible
      irradiation. The samples showed not only good optical absorption in visible
      range, but also great adsorption capacity for methyl orange (MO) dye molecules.
      These properties facilitated the great enhancement of photocatalytic activity of
      TiO2 NPs-coated CNTs photocatalysts. The TiO2 NPs-coated CNTs exhibited 2.45
      times higher photocatalytic activity for MO degradation than that of pure TiO2.

PMID- 20671781
TI  - Mold Fabrication for 3D Dual Damascene Imprinting.
AB  - Previously, a damascene process based on nanoimprint lithography has been
      proposed (Schmid G M, et al. in J Vac Sci Technol B 24(3) 1283, 2006) to greatly
      reduce the fabrication steps of metal interconnection in integrated circuit. For
      such a process to become a viable technique, a mold having two pattern levels
      with precise alignment between them must be fabricated first. To this end, this
      work demonstrates a "self-aligned" fabrication process where the two pattern
      levels would be perfectly aligned if ignoring the noise during e-beam writing.
      The process is based on one EBL on a bi-layer resist stack, with the sensitivity
      for the top layer much higher than that of the bottom layer, which enables
      separate pattern transfer of the two pattern levels. Using ZEP-520A and
      poly(dimethylglutarimide) (PMGI) resists, we fabricated pillars having a diameter
      of 150 nm sitting on ridges having a width of 1.5 mum, which can be used to
      create via-holes and trenches for IC interconnect by nanoimprint lithography. The
      current process can also find applications in other areas that require two-level
      patterning with precise alignment between them.

PMID- 20671782
TI  - Ionic Transport Properties in Nanocrystalline Ce0.8A0.2O2-delta (with A = Eu, Gd,
      Dy, and Ho) Materials.
AB  - The ionic transport properties of nanocrystalline 20 mol% Eu, Gd, Dy, and Ho
      doped cerias, with average grain size of around 14 nm were studied by correlating
      electrical, dielectric properties, and various dynamic parameters. Gd-doped
      nanocrystalline ceria shows higher value of conductivity (i.e., 1.8 * 10-4 S cm-1
      at 550 degrees C) and a lower value of association energy of oxygen vacancies
      with trivalent dopants Gd3+ (i.e., 0.1 eV), compared to others. Mainly the
      lattice parameters and dielectric constants (epsiloninfinity) are found to
      control the association energy of oxygen vacancies in these nanomaterials, which
      in turn resulted in the presence of grain and grain boundary conductivity in Gd-
      and Eu-doped cerias and only significant grain interior conductivity in Dy- and
      Ho-doped cerias.

PMID- 20671783
TI  - Preparation and sustained-release property of triblock copolymer/calcium
      phosphate nanocomposite as nanocarrier for hydrophobic drug.
AB  - The P123/ACP nanocomposite with sizes less than 100 nm consisting of triblock
      copolymer P123 and amorphous calcium phosphate (ACP) has been prepared by using
      an aqueous solution containing CaCl2, (NH4)3PO4, and P123 at room temperature.
      The P123/ACP nanocomposite is used as the nanocarrier for hydrophobic drug
      ibuprofen, based on the combined advantages of both amphiphilic block copolymer
      and calcium phosphate delivery system. The P123/ACP nanocomposite has a much
      higher ibuprofen loading capacity (148 mg/g) than the single-phase calcium
      phosphate nanostructures. The drug release percentage of the P123/ACP
      nanocomposite in simulated body fluid reaches about 100% in a period of 156 h,
      which is much slower than that of single-phase calcium phosphate nanostructures.
      It is expected that the P123/ACP nanocomposite is promising for the application
      in the controlled delivery of hydrophobic drugs.

PMID- 20671784
TI  - Microwave Synthesis of Nearly Monodisperse Core/Multishell Quantum Dots with Cell
      Imaging Applications.
AB  - We report in this article the microwave synthesis of relatively monodisperse,
      highly crystalline CdSe quantum dots (QDs) overcoated with Cd(0.5)Zn(0.5)S/ZnS
      multishells. The as-prepared QDs exhibited narrow photoluminescence bandwidth as
      the consequence of homogeneous size distribution and uniform crystallinity, which
      was confirmed by transmission electron microscopy. A high photoluminescence
      quantum yield up to 80% was measured for the core/multishell nanocrystals.
      Finally, the resulting CdSe/Cd(0.5)Zn(0.5)S/ZnS core/multishell QDs have been
      successfully applied to the labeling and imaging of breast cancer cells (SK-BR3).

PMID- 20671785
TI  - Probing specific interaction forces between human IgG and rat anti-human IgG by
      self-assembled monolayer and atomic force microscopy.
AB  - Interaction forces between biological molecules such as antigen and antibody
      play important roles in many biological processes, but probing these forces
      remains technically challenging. Here, we investigated the specific interaction
      and unbinding forces between human IgG and rat anti-human IgG using self
      assembled monolayer (SAM) method for sample preparation and atomic force
      microscopy (AFM) for interaction force measurement. The specific interaction
      force between human IgG and rat anti-human IgG was found to be 0.6-1.0 nN, and
      the force required for unbinding a single pair of human IgG and rat anti-human
      IgG was calculated to be 144 +/- 11 pN. The results are consistent with those
      reported in the literatures. Therefore, SAM for sample preparation combined with
      AFM for interaction measurement is a relatively simple, sensitive and reliable
      technique to probe specific interactions between biological molecules such as
      antigen and antibody.

PMID- 20671786
TI  - Effects of the Template Composition and Coating on the Photoluminescence
      Properties of ZnS:Mn Nanoparticles.
AB  - Mn-doped ZnS nanocrystals based on low dopant concentrations (0-2%) and coated
      with a shell of Zn(OH)2 have been prepared via soft template and precipitation
      reaction. The results indicate that the ZnS:Mn nanocrystal is cubic zinc blende
      structure and its diameter is 3.02 nm as demonstrated by XRD. Measured by TEM,
      the morphology of nanocrystals is a spherical shape, and their particle size (3-5
      nm) is similar to that of XRD results. Photoluminescence spectra under
      ultraviolet region shows that the volume ratio of alcohol to water in the
      template has a great effect on the luminescence properties of ZnS:Mn particles.
      Compared with unpassivated ZnS:Mn nanocrystals, ZnS:Mn/Zn(OH)2 core/shell
      nanocrystal exhibits much improved luminescence and higher absolute quantum
      efficiency. Meanwhile, we simply explore the formation mechanism of ZnS:Mn
      nanocrystals in alcohol and water system and analyze the reason why alcohol and
      water cluster structures can affect the luminescent properties of nanoparticle.

PMID- 20671787
TI  - Various Quantum- and Nano-Structures by III-V Droplet Epitaxy on GaAs Substrates.
AB  - We report on various self-assembled In(Ga)As nanostructures by droplet epitaxy
      on GaAs substrates using molecular beam epitaxy. Depending on the growth
      condition and index of surfaces, various nanostructures can be fabricated:
      quantum dots (QDs), ring-like and holed-triangular nanostructures. At near room
      temperatures, by limiting surface diffusion of adatoms, the size of In droplets
      suitable for quantum confinement can be fabricated and thus InAs QDs are
      demonstrated on GaAs (100) surface. On the other hand, at relatively higher
      substrate temperatures, by enhancing the surface migrations of In adatoms, super
      lower density of InGaAs ring-shaped nanostructures can be fabricated on GaAs
      (100). Under an identical growth condition, holed-triangular InGaAs
      nanostructures can be fabricated on GaAs type-A surfaces, while ring-shaped
      nanostructures are formed on GaAs (100). The formation mechanism of various
      nanostructures can be understood in terms of intermixing, surface diffusion, and
      surface reconstruction.

PMID- 20671788
TI  - CdTe Quantum Dot/Dye Hybrid System as Photosensitizer for Photodynamic Therapy.
AB  - We have studied the photodynamic properties of novel CdTe quantum dots-methylene
      blue hybrid photosensitizer. Absorption spectroscopy, photoluminescence
      spectroscopy, and fluorescence lifetime imaging of this system reveal efficient
      charge transfer between nanocrystals and the methylene blue dye. Near-infrared
      photoluminescence measurements provide evidence for an increased efficiency of
      singlet oxygen production by the methylene blue dye. In vitro studies on the
      growth of HepG2 and HeLa cancerous cells were also performed, they point toward
      an improvement in the cell kill efficiency for the methylene blue-semiconductor
      nanocrystals hybrid system.

PMID- 20671789
TI  - W18O49 Nanowires as Ultraviolet Photodetector.
AB  - Photodetectors in a configuration of field effect transistor were fabricated
      based on individual W18O49 nanowires. Evaluation of electrical transport behavior
      indicates that the W18O49 nanowires are n-type semiconductors. The photodetectors
      show high sensitivity, stability and reversibility to ultraviolet (UV) light. A
      high photoconductive gain of 104 was obtained, and the photoconductivity is up to
      60 nS upon exposure to 312 nm UV light with an intensity of 1.6 mW/cm2.
      Absorption of oxygen on the surface of W18O49 nanowires has a significant
      influence on the dark conductivity, and the ambient gas can remarkably change the
      conductivity of W18O49 nanowire. The results imply that W18O49 nanowires will be
      promising candidates for fabricating UV photodetectors.

PMID- 20671790
TI  - Superelasticity of Carbon Nanocoils from Atomistic Quantum Simulations.
AB  - A structural model of carbon nanocoils (CNCs) on the basis of carbon nanotubes
      (CNTs) was proposed. The Young's moduli and spring constants of CNCs were
      computed and compared with those of CNTs. Upon elongation and compression, CNCs
      exhibit superelastic properties that are manifested by the nearly invariant
      average bond lengths and the large maximum elastic strain limit. Analysis of bond
      angle distributions shows that the three-dimensional spiral structures of CNCs
      mainly account for their unique superelasticity.

PMID- 20671791
TI  - Random Lasing Action from Randomly Assembled ZnS Nanosheets.
AB  - Lasing characteristics of randomly assembled ZnS nanosheets are studied at room
      temperature. Under 266-nm optical excitation, sharp lasing peaks emitted at
      around 332 nm with a linewidth less than 0.4 nm are observed in all directions.
      In addition, the dependence of lasing threshold intensity with the excitation
      area is shown in good agreement with the random laser theory. Hence, it is
      verified that the lasing characteristics of randomly assembled ZnS nanosheets are
      attributed to coherent random lasing action.

PMID- 20671792
TI  - Influence of Uniaxial Tensile Stress on the Mechanical and Piezoelectric
      Properties of Short-period Ferroelectric Superlattice.
AB  - Tetragonal ferroelectric/ferroelectric BaTiO(3)/PbTiO(3) superlattice under
      uniaxial tensile stress along the c axis is investigated from first principles.
      We show that the calculated ideal tensile strength is 6.85 GPa and that the
      superlattice under the loading of uniaxial tensile stress becomes soft along the
      nonpolar axes. We also find that the appropriately applied uniaxial tensile
      stress can significantly enhance the piezoelectricity for the superlattice, with
      piezoelectric coefficient d(33) increasing from the ground state value by a
      factor of about 8, reaching 678.42 pC/N. The underlying mechanism for the
      enhancement of piezoelectricity is discussed. 

PMID- 20671793
TI  - Template synthesis of carbon nanofibers containing linear mesocage arrays.
AB  - Carbon nanofibers containing linear mesocage arrays were prepared via
      evaporation induced self-assembly method within AAO template with an average
      channel diameter of about 25 nm. The TEM results show that the mesocages have an
      elongated shape in the transversal direction. The results of N2 adsorption
      desorption analysis indicate that the sample possesses a cage-like mesoporous
      structure and the average mesopore size of the sample is about 18 nm.

PMID- 20671794
TI  - On the Chemical Origin of the Gap Bowing in (GaAs)(1-x)Ge(2x) Alloys: A Combined
      DFT-QSGW Study.
AB  - Motivated by the research and analysis of new materials for photovoltaics and by
      the possibility of tailoring their optical properties for improved solar energy
      conversion, we have focused our attention on the (GaAs)(1-x)Ge(2x) series of
      alloys. We have investigated the structural properties of some (GaAs)(1-x)Ge(2x)
      compounds within the local-density approximation to density-functional theory,
      and their optical properties within the Quasiparticle Self-consistent GW
      approximation. The QSGW results confirm the experimental evidence of asymmetric
      bandgap bowing. It is explained in terms of violations of the octet rule, as well
      as in terms of the order-disorder phase transition.

PMID- 20671795
TI  - Preparation and evaluation of poly(ethylene glycol)-poly(lactide) micelles as
      nanocarriers for oral delivery of cyclosporine a.
AB  - A series of monomethoxy poly(ethylene glycol)-poly(lactide) (mPEG-PLA) diblock
      copolymers were designed according to polymer-drug compatibility and synthesized,
      and mPEG-PLA micelle was fabricated and used as a nanocarrier for solubilization
      and oral delivery of Cyclosporine A (CyA). CyA was efficiently encapsulated into
      the micelles with nanoscaled diameter ranged from 60 to 96 nm with a narrow size
      distribution. The favorable stabilities of CyA-loaded polymeric micelles were
      observed in simulated gastric and intestinal fluids. The in vitro drug release
      investigation demonstrated that drug release was retarded by polymeric micelles.
      The enhanced intestinal absorption of CyA-loaded polymeric micelles, which was
      comparable to the commercial formulation of CyA (Sandimmun Neoral(r)), was found.
      These suggested that polymeric micelles might be an effective nanocarrier for
      solubilization of poorly soluble CyA and further improving oral absorption of the
      drug.

PMID- 20671796
TI  - High speed capacitor-inverter based carbon nanotube full adder.
AB  - Carbon Nanotube filed-effect transistor (CNFET) is one of the promising
      alternatives to the MOS transistors. The geometry-dependent threshold voltage is
      one of the CNFET characteristics, which is used in the proposed Full Adder cell.
      In this paper, we present a high speed Full Adder cell using CNFETs based on
      majority-not (Minority) function. Presented design uses eight transistors and
      eight capacitors. Simulation results show significant improvement in terms of
      delay and power-delay product in comparison to contemporary CNFET Adder Cells.
      Simulations were carried out using HSPICE based on CNFET model with 0.6 V VDD.

PMID- 20671797
TI  - Maternal Education, Early Child Care and the Reproduction of Advantage.
AB  - The social and human capital that educational attainment provides women enables
      them to better navigate their children's passages through school. In this study,
      we examine a key mechanism in this intergenerational process: mothers' selection
      of early child care. Analyses of the NICHD Study of Early Child Care and Youth
      Development revealed that maternal education was positively associated with
      configurations of child-care characteristics (i.e., type, quality, quantity) most
      closely linked to children's school readiness. This association was not solely a
      function of mother's income or employment status, persisted despite controls for
      many observable confounds (e.g., maternal cognitive and psychological skills,
      paternal characteristics), and, according to post-hoc indices, was fairly robust
      in terms of unobservable confounds.

PMID- 20671798
TI  - Envisioning a Future Contemplative Science of Mindfulness: Fruitful Methods and
      New Content for the Next Wave of Research.
AB  - Mindfulness is an ancient spiritual practice as well as a unique behavioral
      technique involving the cultivation of non-judgmental, non-reactive,
      metacognitive awareness of present-moment experience. Given the growing interest
      in mindfulness across numerous academic and clinical disciplines, an agenda is
      needed to guide the next wave of research. Here, we suggest four areas that, in
      our view, are important for a future contemplative science of mindfulness:
      performance-based measures of mindfulness, scientific evaluation of Buddhist
      claims, neurophenomenology of mindfulness, and measuring changes in mindfulness
      induced gene expression. By exploring these domains, the wisdom of the meditative
      traditions may be complemented by leading-edge empirical research methodologies.

PMID- 20671799
TI  - Ultrastructural Analysis of Chlamydia Pneumoniae in the Alzheimer's Brain.
AB  - We recently reported identification of the bacterium Chlamydia pneumoniae in
      affected brain regions of patients with Alzheimer's disease (AD) (Balin et al.,
      1998). In this report, we extend those initial observations to demonstrate that,
      in addition to the frequently described, standard morphological forms of the
      organism, pleiomorphic forms are also present in the AD brain. All AD and control
      brain tissues examined were verified to be PCR-positive and negative,
      respectively, for the organism. DNA sequence determination of PCR products so
      derived from total DNA of infected AD brains, as well as from total DNA of cell
      lines infected with the organism following isolation from these same patient
      samples, confirmed the presence of organism in relevant samples. Various
      morphologic forms of C. pneumoniae were identified in PCR-positive tissues and
      these were characterized based on membrane structure, core density, size, and
      immunolabeling profiles. Structures identified include the typical pear-shaped
      elementary body, as well as larger, spherical and oblong reticulate bodies.
      Intact C. pneumoniae were found both intracellularly and extracellularly in the
      sampled autopsy brains. Intracellular organisms were located principally within
      microglia, astroglia, and presumptive pericytes. These results suggest that C.
      pneumoniae found in cells indigenous to the AD brain do not conform universally
      to the classical morphology observed in other infected cell types. This
      pleiomorphism may reflect an adaptive response and/or persistent state of
      infection for these organisms in Alzheimer's Disease.

PMID- 20671800
TI  - Human Embryonic Stem Cells Undergo Osteogenic Differentiation in Human Bone
      Marrow Stromal Cell Microenvironments.
AB  - Human embryonic stem cells (hESCs) may offer an unlimited supply of cells that
      can be directed to differentiate into all cell types within the body and used in
      regenerative medicine for tissue and cell replacement therapies. Previous work
      has shown that exposing hESCs to exogenous factors such as dexamethasone,
      ascorbic acid and beta-glycerophosphate can induce osteogenesis. The specific
      factors that induce osteogenic differentiation of hESCs have not been identified
      yet, however, it is possible that differentiated human bone marrow stromal cells
      (hMBSCs) may secrete factors within the local microenvironment that promote
      osteogenesis. Here we report that the lineage progression of hESCs to osteoblasts
      is achieved in the presence of soluble signaling factors derived from
      differentiated hBMSCs. For 28 days, hESCs were grown in a transwell co-culture
      system with hBMSCs that had been previously differentiated in growth medium
      containing defined osteogenic supplements for 7-24 days. As a control. hESCs were
      co-cultured with undifferentiated hBMSCs and alone. Von Kossa and Alizarin Red
      staining as well as immunohistochemistry confirmed that the hESCs co-cultured
      with differentiated hBMSCs formed mineralized bone nodules and secreted
      extracellular matrix protein osteocalcin (OCN). Quantitative Alizarin Red assays
      showed increased mineralization as compared to the control with undifferentiated
      hBMSCs. RT-PCR revealed the loss of pluripotent hESC markers with the concomitant
      gain of osteoblastic markers such as collagen type I, runx2, and osterix. We
      demonstrate that osteogenic growth factors derived from differentiated hBMSCs
      within the local microenvironment may help to promote hESC osteogenic
      differentiation.

PMID- 20671801
TI  - Developing Early Literacy Skills: A Meta-Analysis of Alphabet Learning and
      Instruction.
AB  - Alphabet knowledge is a hallmark of early literacy and facilitating its
      development has become a primary objective of pre-school instruction and
      intervention. However, little agreement exists about how to promote the
      development of alphabet knowledge effectively. A meta-analysis of the effects of
      instruction on alphabet outcomes demonstrated that instructional impacts differed
      by type of alphabet outcome examined and content of instruction provided. School
      based instruction yielded larger effects than home-based instruction; small-group
      instruction yielded larger effects than individual tutoring programs. We found
      minimal evidence of transfer of alphabet instruction to early phonological,
      reading, or spelling skills. Implications for research and practice are
      discussed.

PMID- 20671802
TI  - AN ASYMPTOTIC SAMPLING FORMULA FOR THE COALESCENT WITH RECOMBINATION.
AB  - Ewens sampling formula (ESF) is a one-parameter family of probability
      distributions with a number of intriguing combinatorial connections. This elegant
      closed-form formula first arose in biology as the stationary probability
      distribution of a sample configuration at one locus under the infinite-alleles
      model of mutation. Since its discovery in the early 1970s, the ESF has been used
      in various biological applications, and has sparked several interesting
      mathematical generalizations. In the population genetics community, extending the
      underlying random-mating model to include recombination has received much
      attention in the past, but no general closed-form sampling formula is currently
      known even for the simplest extension, that is, a model with two loci. In this
      paper, we show that it is possible to obtain useful closed-form results in the
      case the population-scaled recombination rate rho is large but not necessarily
      infinite. Specifically, we consider an asymptotic expansion of the two-locus
      sampling formula in inverse powers of rho and obtain closed-form expressions for
      the first few terms in the expansion. Our asymptotic sampling formula applies to
      arbitrary sample sizes and configurations.

PMID- 20671803
TI  - TOWARDS PATIENT-CENTERED CARE FOR DEPRESSION: CONJOINT METHODS TO TAILOR
      TREATMENT BASED ON PREFERENCES.
AB  - BACKGROUND: Although antidepressants and counseling have been shown to be
      effective in treating patients with depression, non-treatment or under-treatment
      for depression is common especially among the elderly and minorities. Previous
      work on patient preferences has focused on medication versus counseling, but less
      is known about the value patients place on attributes of medication and
      counseling.  OBJECTIVE: Conjoint analysis has been recognized as a valuable means
      of assessing patient treatment preferences. We examine how conjoint analysis be
      used to determine the relative importance of various attributes of depression
      treatment at the group level as well as to determine the range of individual
      level relative preference weights for specific depression treatment attributes.
      In addition we use conjoint analysis to predict what modifications in treatment
      characteristics are associated with a change in the stated preferred alternative.
      STUDY DESIGN: 86 adults who participated in an internet-based panel responded to
      an on-line discrete choice task about depression treatment. Participants chose
      between medication and counseling based on choice sets presented first for a
      "mild depression" scenario and then for a "severe depression" scenario.
      Participants were given 18 choice sets which varied for medication based on type
      of side effect (nausea, dizziness, and sexual dysfunction) and severity of side
      effect (mild, moderate, and severe); and for counseling based on frequency of
      counseling sessions (once per week or every other week) and location of the
      sessions (mental health professional's office, primary care doctor's office or
      office of a spiritual counselor).  RESULTS: Treatment type (counseling vs.
      medication) appeared to be more important in driving treatment choice than any
      specific attribute that was studied. Specifically counseling was preferred by
      most of the respondents. After treatment type, location of treatment and
      frequency of treatment were important considerations. Preferred attributes were
      similar in both the mild and severe depression scenarios. Side effect severity
      appeared to be most important in driving treatment choice as compared with the
      other attributes studied. Individual-level relative preferences for treatment
      type revealed a distribution that was roughly bimodal with 27 participants who
      had a strong preference for counseling and 14 respondents who had a strong
      preference for medication.  CONCLUSION: Estimating individual-level preferences
      for treatment type allowed us to see the variability in preferences and determine
      which participants had a strong affinity for medication or counseling.

PMID- 20671805
TI  - The Connecticut Center of Excellence for Eliminating Health Disparities among
      Latinos (CEHDL).
AB  - CEHDL's mission is to contribute to the elimination of health disparities among
      Latino(a)s through the formation of human resources, community-based research,
      and culturally appropriate outreach/extension. CEHDL is structured as a
      consortium led by the University of Connecticut (UConn) in close partnership with
      the Hispanic Health Council (HHC), a community health agency located in inner
      city Hartford, and Hartford Hospital (HH). Demonstrating best practice and
      culturally skilled, evidence-based outreach, and bringing the best of academic,
      community, and health institutions to socioeconomically disadvantaged
      communities, CEHDL fosters scientific-community interactions and supports
      training of undergraduate, graduate, and medical students. Building capacity in
      other agencies is one method through which CEDHDL seeks to accomplish its goals.
      Thus far, CEHDL has made substantial progress demonstrating that
      interdisciplinary community-academic-hospital partnerships are essential for
      addressing health inequities in our country.

PMID- 20671804
TI  - Histopathological image analysis: a review.
AB  - Over the past decade, dramatic increases in computational power and improvement
      in image analysis algorithms have allowed the development of powerful computer
      assisted analytical approaches to radiological data. With the recent advent of
      whole slide digital scanners, tissue histopathology slides can now be digitized
      and stored in digital image form. Consequently, digitized tissue histopathology
      has now become amenable to the application of computerized image analysis and
      machine learning techniques. Analogous to the role of computer-assisted diagnosis
      (CAD) algorithms in medical imaging to complement the opinion of a radiologist,
      CAD algorithms have begun to be developed for disease detection, diagnosis, and
      prognosis prediction to complement the opinion of the pathologist. In this paper,
      we review the recent state of the art CAD technology for digitized
      histopathology. This paper also briefly describes the development and application
      of novel image analysis technology for a few specific histopathology related
      problems being pursued in the United States and Europe.

PMID- 20671806
TI  - A Superconducting Joint Technique for MgB(2) Round Wires.
AB  - This paper describes a technique to superconductively splice multifilament MgB(2)
      wires. To date the technique has achieved joints capable of carrying a
      superconducting current of 200 A at 10 K in self field. Joints details, as well
      as testing methods and results are presented here.

PMID- 20671807
TI  - Data Collection Order: A Primer.

PMID- 20671808
TI  - THE OTHER PATENT AGENCY: CONGRESSIONAL REGULATION OF THE ITC.
AB  - The United States International Trade Commission has recently experienced a
      dramatic increase in patent infringement investigations under section sign 337 of
      the Tariff Act of 1930. In fact, the number of patent enforcement actions
      submitted to the ITC has nearly doubled in the last five years. Patent holders
      are selecting this forum because of its speedy proceedings and its ability to
      award broad exclusion orders. This rise in ITC patent litigation, however, has
      revealed weaknesses in the structure of section sign 337. In broadening the
      provision to facilitate the enforcement of patent rights, Congress failed to
      consider the impact of this change on technological innovation and on the
      coherence of the patent system. In particular, Congress did not clarify the
      relationship between section sign 337 and the Patent Act, thereby jeopardizing
      the uniformity of the patent system. Nor did it consider the effect that patent
      related exclusion orders would have on innovation and on strategic behavior. This
      Article recommends that Congress harmonize ITC patent law with the Patent Act and
      related federal precedent, or alternatively, abolish section sign 337.

PMID- 20671810
TI  - Paternal Depressive Symptoms and Adolescent Functioning: The Moderating Effect of
      Gender and Father Hostility.
AB  - This study examined the longitudinal relationship between paternal depressive
      symptoms, paternal hostility, and adolescent functioning in a community sample of
      451 families. Paternal depressive symptoms were a strong predictor of adolescent
      outcome, even after controlling for family demographic variables, maternal
      depressive symptoms, and previous adolescent symptoms. Adolescent gender and
      perception of paternal hostility moderated this association such that females
      reporting high paternal hostility were particularly vulnerable to the adverse
      effects of paternal depressive symptoms. Maternal and paternal depressive
      symptoms had an additive, rather than interactive, effect on adolescent
      functioning. These results contribute to our knowledge of the interpersonal
      processes by which depression runs in families and highlight the importance of
      including fathers in developmental research on adolescent internalizing problems.

PMID- 20671811
TI  - Spatial Heterogeneity in the Effects of Immigration and Diversity on Neighborhood
      Homicide Rates.
AB  - This paper examines the connection of immigration and diversity to homicide by
      advancing a recently developed approach to modeling spatial dynamics
      geographically weighted regression. In contrast to traditional global averaging,
      we argue on substantive grounds that neighborhood characteristics vary in their
      effects across neighborhood space, a process of "spatial heterogeneity." Much
      like treatment-effect heterogeneity and distinct from spatial spillover, our
      analysis finds considerable evidence that neighborhood characteristics in Chicago
      vary significantly in predicting homicide, in some cases showing countervailing
      effects depending on spatial location. In general, however, immigrant
      concentration is either unrelated or inversely related to homicide, whereas
      language diversity is consistently linked to lower homicide. The results shed new
      light on the immigration-homicide nexus and suggest the pitfalls of global
      averaging models that hide the reality of a highly diversified and spatially
      stratified metropolis.

PMID- 20671809
TI  - The phosphatidylinositol 3-kinase/Akt/mTOR signaling network as a therapeutic
      target in acute myelogenous leukemia patients.
AB  - The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR)
      signaling axis plays a central role in cell proliferation, growth, and survival
      under physiological conditions. However, aberrant PI3K/Akt/mTOR signaling has
      been implicated in many human cancers, including acute myelogenous leukemia
      (AML). Therefore, the PI3K/Akt/mTOR network is considered as a validated target
      for innovative cancer therapy. The limit of acceptable toxicity for standard
      polychemotherapy has been reached in AML. Novel therapeutic strategies are
      therefore needed. This review highlights how the PI3K/Akt/mTOR signaling axis is
      constitutively active in AML patients, where it affects survival, proliferation,
      and drug-resistance of leukemic cells including leukemic stem cells. Effective
      targeting of this pathway with small molecule kinase inhibitors, employed alone
      or in combination with other drugs, could result in the suppression of leukemic
      cell growth. Furthermore, targeting the PI3K/Akt/mTOR signaling network with
      small pharmacological inhibitors, employed either alone or in combinations with
      other drugs, may result in less toxic and more efficacious treatment of AML
      patients. Efforts to exploit pharmacological inhibitors of the PI3K/Akt/mTOR
      cascade which show efficacy and safety in the clinical setting are now underway.

PMID- 20671812
TI  - The Importance of Audience and Agency for Representation: A Case Study of an
      Urban Youth Media Community.
AB  - PURPOSE: Urban youths' agency to represent their realities through media has been
      largely unexplored in the youth development literature. In this qualitative case
      study of an after-school youth media program in the Bay Area, expressions of
      youth agency and the role of audiences are explored during the process of
      producing videos for public consumption. METHODOLOGY: As participant observer of
      14 ethnically diverse youth participants aged between 15 and 18 years over 18
      months, I documented (a) the kind of agencies participants engaged in and (b) the
      impact of live and imagined future audiences on youths' creative processes.
      Analyses of field notes, semi-structured interviews, and media projects were
      conducted using thematic analysis to inductively generate emerging categories.
      FINDINGS: Themes included an agentive sense of self-efficacy, commitment, and
      responsibility, as well as perceived contributions to local audiences and an
      emerging collective identity. The youth demonstrated their increased sense of a
      social or civic duty to realistically represent youth of color to familiar and
      unfamiliar audiences. IMPLICATIONS: This case study demonstrated how one youth
      media organization fostered agency through youth authorship, production,
      distribution, and local community dialogue. By documenting the impact of
      audiences from conception to public reception, this study provides valuable
      insight into the agentive process of publicly "performing" a commitment to
      complete a social change video project. CONTRIBUTION: This chapter underscores
      the value of performance within youth development programs and the critical
      component of audiences as one form of authentic assessment in order to foster
      individual and collective agency.

PMID- 20671813
TI  - Helping Clients Feel Welcome: Principles of Adapting Treatment Cross-Culturally.
AB  - Empirically supported interventions (ESIs) for treating substance problems have
      seldom been made available to or tested with minority populations. Dissemination
      of ESIs may help reduce the disproportionate health disparities that exist.
      However, ESIs may require some adaptation to be effective with minority
      populations. One ESI, motivational interviewing (MI), appears to be particularly
      culturally congruent for Native American communities. We worked with Native
      American community members and treatment providers to adapt MI for Native
      communities. Reflecting their feedback and suggested amendments, we created and
      disseminated an intervention manual to improve the accessibility of MI within
      Native communities. To help guide practitioners working with Native American
      clients, we used focus-group methodology to explore communication patterns for
      negotiating change. Native American treatment providers expressed comfort with
      and enthusiasm for integrating MI into their current practices. Recommendations
      for adaptations ranged from simple to complex changes. The unique value and
      challenges of collaboration between academic and community members are presented
      from each author's perspective. This culturally adapted MI manual will likely
      improve the accessibility and adoption of MI practices as well as encourage
      controlled, clinical trials with Native communities.

PMID- 20671814
TI  - Reaction of the Anticancer Organometallic Ruthenium Compound, [(eta-p
      Cymene)Ru(ATSC)Cl]PF(6) with Human Serum Albumin.
AB  - The reaction of [(eta(6)-p-cymene)Ru(ATSC)Cl]PF(6) (ATSC = 9-anthraldehyde
      thiosemicarbazone) with human serum albumin was investigated at different
      temperatures using fluorescence and infrared spectrophotometry. The binding
      constant, K, for the reaction was determined using a number of different methods.
      Using a modified Stern-Volmer equation, K was determined to be 9.09 x 10(4), 12.1
      x 10(4), and 13.1 x 10(4) M(-1) at 293 K, 298 K, and 308 K, respectively. A
      thermodynamic analysis showed that the reaction is spontaneous with DeltaG being
      negative. The enthalpy of reaction DeltaH = 16.5kJ mol(-1) and the entropy of
      reaction DeltaS = 152 Jmol(-1)K(-1). The values of DeltaH and DeltaS suggest that
      hydrophobic forces are dominant in the mode of interaction and that the process
      is mostly entropy driven.

PMID- 20671815
TI  - Evaluation of J-initiation fracture toughness of ultra high molecular weight
      polyethylene used in total joint replacements.
AB  - Fracture of ultra high molecular weight polyethylene (UHMWPE) total joint
      replacement components is a clinical concern. Thus, it is important to
      characterize the fracture resistance of UHMWPE. To determine J-initiation
      fracture toughness (J(Q)) for metals and metallic alloys, ASTM E1820 recommends a
      procedure based on an empirical crack blunting line. This approach has been found
      to overestimate the initiation toughness of tough polymers like UHMWPE.
      Therefore, in this study, a novel experimental approach based on crack tip
      opening displacement (CTOD) was utilized to evaluate J(Q) of UHMWPE materials. J
      initiation fracture toughness was experimentally measured in ambient air and a
      physiologically-relevant 37 degrees C PBS environment for three different
      formulations of UHMWPE and compared to the blunting line approach. The CTOD
      method was found to provide J(Q) values comparable to the blunting line approach
      for the UHMWPE materials and environments examined in this study. The CTOD method
      used in this study is based on experimental observation and, thus, does not rely
      on an empirical relationship or fracture surface measurements. Therefore,
      determining J(Q) using the experimentally based CTOD method proposed in this
      study may be a more reliable approach for UHMWPE and other tough polymers than
      the blunting line approach.

PMID- 20671816
TI  - Approaches to chronic disease management for asthma and chronic obstructive
      pulmonary disease: strategies through the continuum of care.
AB  - Investigator-initiated research in both asthma and chronic obstructive pulmonary
      disease conducted at the Baylor Martha Foster Lung Care Center has sought to
      improve management throughout the continuum of respiratory care using a
      multidisciplinary approach. Respiratory care therapists employed in the primary
      care setting were shown to improve the quality of asthma care: rescue inhaler use
      decreased by 75% and respiratory symptom score decreased by 49% in patients who
      were seen by this midlevel specialty provider. In addition to similar results in
      a geriatric population, patients' diagnosis was changed in 48% of cases and
      treatment was changed in 76% of cases after the intervention. For pulmonary
      rehabilitation, an activity of daily living assessment form was created, and
      rehabilitation-whether traditional or water-based-was shown to improve patients'
      ability to perform activities of daily living and improve quality of life scores.
      The Rules of Two((R)), developed by Baylor University Medical Center at Dallas to
      simplify understanding of good asthma control, continues to be taught, and
      patient education has also been offered through asthma summer camps for children.
      Finally, a multidisciplinary team worked to develop a protocol for treatment of
      asthma patients in the emergency department and, through this effort, was able to
      reduce length of stay from an average of 278 minutes to an average of 168
      minutes. These efforts aim to overcome the gap between recommended care and
      actual practice, so that patients benefit from evidence-based medicine and
      continuing refinements to diagnosis and treatment.

PMID- 20671817
TI  - Chronic disease management for diabetes: Baylor Health Care System's coordinated
      efforts and the opening of the Diabetes Health and Wellness Institute.

PMID- 20671818
TI  - Implementation of the first wellness-fitness evaluation for the Dallas Fire
      Rescue Department.
AB  - More than 100 firefighters lose their lives in the line of duty each year; many
      of these deaths are caused by cardiovascular events and underlying coronary heart
      disease. In addition, firefighters are at higher-than-normal risk of developing
      certain types of cancer. To improve health and fitness among its firefighters,
      the Dallas Fire-Rescue Department developed and implemented an annual wellness
      fitness program in 2008. The program detected and addressed medical issues
      including coronary disease, hypertension, high triglyceride levels, high
      cholesterol, high blood glucose levels, and hematuria. Prostate, thyroid, breast,
      kidney, and bladder cancers were also detected. By identifying these issues,
      engaging the firefighters' personal physicians, and recommending individualized
      treatment plans, this program may have extended lives and improved the quality of
      life for the firefighters.

PMID- 20671819
TI  - Optimizing blood pressure control in patients with chronic kidney disease.
AB  - The majority of patients with chronic kidney disease have hypertension, which is
      an independent risk factor for progression of kidney disease and cardiovascular
      disease. Therefore, hypertension should be stringently controlled to a blood
      pressure level of <130/80 mm Hg. Achieving this goal, which usually requires two
      or more antihypertensive agents, slows the progression of kidney disease and
      reduces the risk of cardiovascular disease. All antihypertensive treatments for
      patients with chronic kidney disease should include a renin-angiotensin
      aldosterone system (RAAS) inhibitor (an angiotensin-converting enzyme inhibitor
      or an angiotensin receptor blocker). Initial therapy with fixed-dose RAAS
      inhibitor-based combinations should be considered, because this approach has been
      shown to bring significantly more patients to target blood pressure levels,
      compared with stepped-care treatment or sequential monotherapy. Fixed-dose
      combination therapy may also improve patient adherence to treatment by reducing
      the number of pills taken daily and the number of office visits for dosage
      adjustments. Recent clinical data suggest that the combination of a RAAS
      inhibitor and a dihydropyridine calcium channel blocker may provide more
      cardiovascular benefit than the generally recommended combination of a RAAS
      inhibitor and a diuretic in patients at high risk for cardiovascular events.

PMID- 20671820
TI  - Current opinions in renovascular hypertension.
AB  - Renal artery stenosis and renovascular hypertension are important considerations
      in patients with hypertension that is difficult to control. The diagnosis may
      also have prognostic significance for progressive renal disease. The most common
      causes of renal artery stenosis are atherosclerotic disease and fibromuscular
      dysplasia. The pathophysiology of renal artery stenosis is reviewed, and the pros
      and cons of various imaging studies in the appropriate clinical setting are
      discussed. Treatment includes aggressive control of hypertension, dealing with
      associated cardiac risk factors, and angioplasty or surgery in specific
      circumstances.

PMID- 20671821
TI  - Causes and management of drug-induced long QT syndrome.
AB  - Long QT syndrome (LQTS) is characterized by inherited or acquired prolonged QT
      interval on the surface electrocardiogram. This can lead to torsade de pointes
      ventricular tachycardia (TdP VT) and ventricular fibrillation. In the acquired
      form of the disease, medications from several classes can cause TdP VT or
      potentiate the electrocardiographic findings. These include class IA and III
      antiarrhythmics, antibiotics (macrolides and quinolones), antidepressants
      (tricyclics and selective serotonin reuptake inhibitors), antipsychotics
      (haloperidol and phenothiazines), and antiemetics (ondansetron and
      prochlorperazine). We present four cases of drug-induced LQTS resulting in life
      threatening cardiac arrhythmias. Antiarrhythmic medications were the cause in two
      cases, and the other two cases involved noncardiac medications. All four patients
      had at least one risk factor for LQTS in addition to the offending drug,
      including female gender, hypokalemia, hypomagnesemia, and bradycardia. In one
      patient, amiodarone was administered for treatment of VT, although the correct
      diagnosis was actually TdP VT. In patients with polymorphic VT or ventricular
      fibrillation without a significant history of cardiovascular disease, drug
      induced LQTS should be high in the differential diagnosis. Prompt diagnosis is
      key, as amiodarone, while often used to suppress VT, is potentially harmful in
      the setting of LQTS and TdP VT.

PMID- 20671822
TI  - Pacemaker laser lead extraction and reimplantation of dual-chamber implantable
      cardioverter defibrillator via Mustard baffle in complete transposition of great
      arteries.
AB  - We present a case of a complicated lead extraction and reimplantation of an
      implantable cardioverter defibrillator (ICD) in a young woman with complete
      transposition of great arteries (CTGA), a cyanotic congenital heart defect in
      which the aorta and the pulmonary trunk are transposed. The malformation results
      in two parallel circulations, whereby the left ventricle is attached to the
      pulmonary trunk and the right ventricle is attached to the aorta. Survival
      depends on the mixing of these two circulations at the level of the atria or
      ventricles or great arteries. Balloon atrial septostomy and creation of an intra
      atrial baffle are procedures that increase atrial mixing, increase systemic
      oxygenation, and hence improve survival. With the improved survival of patients
      with CTGA, there is an increasing need for permanent pacemakers (PPMs) and ICDs
      for rhythm disturbances. These leads and/or devices are often inserted when the
      patients are very young and need to be replaced or explanted in adulthood due to
      device or lead malfunction, device-associated infection, or generator replacement
      or upgrades. These procedures are often complicated by the patients' complex
      anatomy and/or shunts. We describe a patient with CTGA who had an intra-atrial
      baffle and a nonfunctioning dual-chamber PPM. The lead was extracted via the
      baffle and the old PPM was upgraded to an ICD. Such descriptions are rare.

PMID- 20671823
TI  - Study of a European male champion in 10-km road races in the age group >85 years.
AB  - An 86-year-old man became a double champion in the European championship for road
      running in 2009. He won the 10-km road run with a time of 58:01 minutes, setting
      a new European record for men aged 85 and older. Two days later, he became a
      European champion in the same age group for the half-marathon, with a time of
      2:17 hours. He started his running career at the age of 64 years and has trained
      for about an hour three times a week every year since. During these 22 years, he
      has performed several road runs each year, ranging from 2.5 to 10 km, and also
      completed a number of half-marathons. Although his running speeds had
      progressively slowed since the age of 64, there was an increased rate of decline
      at the age of 82. This man's outstanding performance should encourage other
      master runners to continue running and competing past the age of 85.

PMID- 20671824
TI  - Frostbite.

PMID- 20671825
TI  - Samuel Wilks: the "grand old man" of British medicine.

PMID- 20671826
TI  - Thirty-three years after bypass surgery: a heart patient's perspective.

PMID- 20671827
TI  - Joseph Charles Piscatella: a conversation with the editor.

PMID- 20671828
TI  - Daniel Carl DeMarco, MD: a conversation with the editor.

PMID- 20671829
TI  - Gender and blindness: Taking a global and a local perspective.

PMID- 20671830
TI  - Imaging in neuro-ophthalmology: An overview.
AB  - Advances in neuroimaging and interventional techniques have revolutionized the
      early diagnosis, prognosis, and treatment of neuro-ophthalmic disorders. These
      techniques include computed tomography (CT), magnetic resonance imaging (MRI), CT
      and MR angiographic techniques, catheter digital subtraction angiography,
      functional MRI, positron emission tomography, and single photon emission computed
      tomography. In this review, the value of current techniques in the diagnosis,
      localization, and treatment of various neuro-ophthalmic disorders is described.

PMID- 20671831
TI  - Effect of macular photocoagulation on visual acuity of Omani patients with
      clinically significant macular edema.
AB  - BACKGROUND: The aim of this study was to determine the effect of macular laser
      treatment on the visual acuity (VA) of Omani diabetic patients with clinically
      significant macular edema (CSME). Visual outcome was also correlated with
      duration and control of diabetes and presence or absence of hypertension and
      hyperlipidemia. MATERIALS AND METHODS: This is a retrospective noncomparative
      cohort study involving 101 eyes of 72 Omani diabetic patients. Change in VA was
      determined using Snellen's VA chart. The mean duration of follow-up was
      approximately 21 months (range, 16-24 months). RESULTS: 29.7% of the patients
      maintained their vision, 35.6% showed improvement, whereas 34.7% showed a
      decrease in their vision. Positive visual outcome showed a statistically
      significant direct relationship with tight control of diabetes and absence of
      hypertension and an inverse relationship with the duration of diabetes. Presence
      of hyperlipedemia did not show a statistically significant relationship with
      positive visual outcome. However, it showed a trend to better visual outcome in
      the absence of hyperlipedemia. Peak incidence of macular edema was seen at the
      age of 52.3 years. CONCLUSION: Macular photocoagulation was found to be an
      effective method of treatment for CSME among Omani diabetic patients, which has
      resulted in a positive visual outcome in 65.3% of the patients (stable and
      improved vision). Effective control of diabetes, duration of diabetes, and
      hypertension are the factors which influence the postlaser visual outcome.

PMID- 20671832
TI  - Compliance of amblyopic patients with occlusion therapy: A pilot study.
AB  - BACKGROUND: Increasing evidence shows that good compliance with occlusion therapy
      is paramount for successful amblyopia therapy. PURPOSE: To study the degree of
      compliance and explore factors affecting compliance in patients undergoing
      occlusion therapy for amblyopia in our practice. DESIGN: Nonrandomized clinical
      intervention study. MATERIALS AND METHODS: A total of 31 families with a child
      (aged 2-12 years), undergoing unilateral amblyopia treatment at the pediatric
      ophthalmology clinic of Sultan Qaboos University Hospital, Oman, were recruited
      for this one month study. Parents were interviewed and completed a closed-ended
      questionnaire. Clinical data including, visual acuity, refraction, diagnosis and
      treatment, for each patient was collected from the hospital chart and was entered
      in a data collection sheet. Compliance with occlusion therapy was assessed by
      self-report accounts of parents and was graded into good, partial, or poor.
      Association between various factors and degree of compliance was studied using
      logistic regression modeling. RESULTS: Only 14 (45%) patients showed good
      compliance to occlusion therapy. 17 (55%) patients were noncompliant. Improvement
      in visual acuity strongly correlated with compliance to patching (P = 0.008).
      Other variables that were studied included, age at onset of therapy; gender;
      degree of amblyopia; type of amblyopia; use of glasses; and compliance with
      glasses. These did not emerge as significant predictors of compliance. All but
      one family with poor compliance stated that the main challenge in following the
      recommendation to patch for requisite hours was in getting their child to
      cooperate. Only in one instance, the family cited nonavailability of patches as
      the main hindrance to compliance. 10/31 (32%) families expressed a desire for
      more information and 18/31 (58%) parents did not understand that amblyopia meant
      decreased vision. CONCLUSION: Poor compliance is a barrier to successful
      amblyopia therapy in our practice. Improvement in visual acuity is associated
      with better compliance with patching. Parents find it difficult to comprehend and
      retain verbal explanations of various components regarding occlusion therapy for
      amblyopia. Future study with a larger sample of patients is recommended to
      investigate the factors affecting compliance with amblyopia therapy and determine
      predictors for poor compliance.

PMID- 20671833
TI  - Bevacizumab therapy for macular edema in central retinal vein occlusion: Long
      term results.
AB  - BACKGROUND: There is no proven effective treatment for vision loss in central
      retinal vein occlusion (CRVO). Bevacizumab has been reported in small series with
      limited follow-up, to have a positive effect in reducing cystoid macular edema
      (CME) and improving vision in CRVO. PURPOSE: To report long-term results with the
      use of bevacizumab in CRVO. MATERIALS AND METHODS: Prospective interventional
      case series included 15 patients, serially evaluated with best corrected visual
      acuity (BCVA), optical coherence tomography (OCT), fluorescein angiography, and
      tonometry. Results were statistically analyzed. RESULTS: Mean follow-up was 12 +/
      3.6 months (range, 6-18 months); mean number of injections was 2.2 (range, 1-4)
      per patient. Statistically significant reduction of macular thickness (P < 0.001)
      was seen at six weeks (mean, 346 mu); three months (mean, 353 mu); six months
      (mean, 348 mu); and final follow-up (mean, 342 mu). Significant BCVA improvement
      was seen at six weeks (mean, 0.27 logMAR), three months (mean, 0.3 logMAR), three
      months (0.15 logMAR), and final follow-up (mean, 0.21 logMAR) (P = 0.009). Also,
      73.3% patients had BCVA improvement at the last follow-up. CONCLUSION:
      Intravitreal bevacizumab is an effective treatment option for CME in CRVO
      patients. Reinjections at appropriate timing, based on the OCT findings, are
      important for better visual outcome.

PMID- 20671834
TI  - Bilateral coexistence of keratoconus and macular corneal dystrophy.
AB  - Bilateral coexistence of keratoconus and macular corneal dystrophy is a very rare
      clinical entity. Further elaboration on the possible genetic, histopathologic,
      pathophysiologic and biochemical correlation is required to study the nature of
      the condition.The authors hereby report a 21-year-old female who presented with
      the typical signs and topographic evidence of keratoconus in association with
      macular corneal dystrophy. Histopathologic evaluation from the excised corneal
      button after corneal transplant confirmed the diagnosis.To our knowledge, there
      is only one previous report in the literature linking the association of
      keratoconus and macular corneal dystrophy in the same eye bilaterally.

PMID- 20671835
TI  - A case of von Hippel-Lindau disease with exudative maculopathy.
AB  - Von Hippel-Lindau (VHL) disease is a rare multisystem familial tumor syndrome of
      autosomal dominant inheritance. Hallmark lesions include retinal, cerebellum and
      spinal cord hemangioblastomas, renal cell carcinomas, adrenal pheochromocytomas,
      angiomatous or cystic lesions of the kidneys, pancreas, and epididymis. We report
      a case of VHL disease in a 26-year-old patient who presented with exudative
      macular edema. Ocular and systemic studies revealed the presence of retinal and
      central nervous system hemangioblastomas, adrenal pheochromocytoma, multiple
      pancreatic, and kidney cysts. The retinal angiomas were successfully treated with
      argon laser photocoagulation and cryotherapy.

PMID- 20671836
TI  - Hemophilia of orbit.
AB  - Hemophilic pseudotumor is an uncommon complication of factor VIII and IX
      deficiencies in the coagulation cascade and occurs in a wide spectrum of bones
      and soft tissues. We present a six-year-old boy with hemophilic pseudotumor
      localized in the right orbit. He showed a favorable response to radiation therapy
      after unsuccessful treatment with factor VIII replacement therapy with no
      recurrence till eight months. Radiotherapy in the treatment of pseudotumors in
      hemophiliacs should be strongly considered, particularly in severely affected
      patients who do not respond to conservative therapy.

PMID- 20671837
TI  - Transpalpebral extrusion of solid silicone buckle.
AB  - Explants used in retinal reattachment surgery occasionally extrude. Cheese-wiring
      of the suture through the sclera consequent to raised intraocular pressure allows
      the buckle to loosen and/or unfold. Subsequent infection, often with
      Staphylococcus albus, accelerates the process of extrusion. Commonly, such
      explants are of silicone sponge. The reported case is unusual in that the
      extrusion occurred through the upper lid, and involved a solid silicone explant.

PMID- 20671838
TI  - Iridescent anterior chamber crystals following minor ocular trauma.
AB  - Anterior chamber crystals occur due to severe ocular trauma or chronic
      inflammation. The affected eye has often suffered irreversible visual loss.
      Iridescent crystals are rare and they have interesting clinical features which
      have been reported commonly among Caucasian populations. This condition has never
      been reported in an African patient. A 21-year-old Nigerian woman presented with
      a history of trauma to the left eye and subsequent progressive loss of vision.
      Polychromatic crystals were observed incidentally in the anterior chamber. This
      is the first report of this unusual clinical condition in an African patient.

PMID- 20671839
TI  - Rebound effect following intravitreal bevacizumab in branch retinal vein
      occlusion.

PMID- 20671840
TI  - Orbital pseudotumor.

PMID- 20671841
TI  - 8-year-old boy with reduced vision in both eyes.

PMID- 20671842
TI  - Acute uveitis following zoledronic acid infusion.

PMID- 20671843
TI  - Eye care through private sector in Oman.

PMID- 20671844
TI  - Pediatric urology: Development, eligibility, practice.

PMID- 20671845
TI  - Anatomical basis for Wilms tumor surgery.
AB  - Wilms tumor surgery requires meticulous planning and sophisticated surgical
      technique. Detailed anatomical knowledge can facilitate the uneventful
      performance of tumor nephrectomy and cannot be replaced by advanced and
      sophisticated imaging techniques. We can define two main goals for surgery: (1)
      exact staging as well as (2) safe and complete resection of tumor without
      spillage. This review aims to review the anatomical basis for Wilms tumor
      surgery. It focuses on the surgical anatomy of retroperitoneal space, aorta, vena
      cava and their large branches with lymphatics. Types and management of vascular
      injuries are discussed.

PMID- 20671846
TI  - Psychological issues in cleft lip and cleft palate.
AB  - Vocational and social issues affect rehabilitation and development of patients
      with cleft lip and cleft palate. However, psychological problems like lowered
      self esteem and difficulties in social interaction have also been noted in them.
      Not many pediatric reconstructive surgery teams have a psychiatrist on their
      panel. It is likely that psychological problems are higher in incidence than
      literature actually suggests. Hence it is very essential that such cases are
      identified by the surgical team to maximize positive outcome of surgery and
      rehabilitation. This study discusses psychological issues revolving around cleft
      lip and cleft palate along with lacunae in many psychological research studies.

PMID- 20671847
TI  - Hirschsprung's disease diagnosis: Comparison of immunohistochemical, hematoxilin
      and eosin staining.
AB  - BACKGROUND: The diagnosis of Hirschsprung's disease (HD) is based on the absence
      of ganglion cells. In hemotoxilin and eosin (H and E) as well as acetylcholine
      esterase staining there are limitations in the diagnosis of immature ganglion
      cells in neonates. METHODS: In this prospective study, 54 biopsies taken from
      suspected HD patients (five mucosal specimens and 49 full thickness specimens)
      were studied. In the laboratory, after preparing sections of paraffin embedded
      tissues, H and E staining slides were compared with immunohistochemical (IHC)
      staining including: S100, NSE, CD117, CD56, Cathepsin D, Vimentin, BCL2, GFAP,
      Synaptophysin and chromogranin. RESULTS: The study revealed 30 negative (absence
      of ganglion cells) cases (55.5%), 17 positive cases (31.04%) and seven suspected
      cases (12.9%) of ganglion cells on the H and E staining. On IHC staining with
      CD56 and Cathepsin D, all of the 17 positive cases detected through H and E, were
      confirmed for having ganglion cells and out of 30 cases reported negative on H
      and E staining, 28(93.3%) were reported negative and two (6.7%) positive by IHC
      staining. Of the seven suspected cases H and E staining), IHC staining
      detectedganglion cells only in five slides; two remained negative. CONCLUSIONS:
      IHC staining using CD56 and Cathepsin D improved the accuracy of diagnosis in HD
      when used in addition to H and E staining technique, especially for negative or
      suspicious slides.

PMID- 20671848
TI  - Flexible ureterorenoscopy and laser lithotripsy in children.
AB  - BACKGROUND: Flexible ureterorenoscopy (FUR) and laser lithotripsy (LL) are
      techniques used in the management of upper urinary tract disorders. These
      techniques, so far established in adults, are now being used in children as well.
      We report our experience with 26 cases of pediatric upper urinary tract disorders
      treated using these techniques. METHODS: In the period from 1997 to 2006, FUR was
      performed in 26 children (14 males and 12 females) in the age group of three
      months to 15 years with a mean age of 8.2 years. Twenty five were stented prior
      to undergoing FUR and 24 presented with suspected upper tract stones (17
      pelvicalyceal and seven midureteric). Two cases showed JJ stent migration post
      pyeloplasty. RESULTS: Eight cases involved diagnostic procedures. Six excluded
      the presence of renal calculi, one had focal medullary sponge kidney, and one had
      calcified papillae. There were 15 cases of therapeutic FUR. Of these, 12 had LL
      with only one had incomplete stone fragmentation which subsequently passed
      spontaneously. Other therapeutic procedures included removal of migrated JJ
      stents and FUR with the basket removal of a midureteric calculus. Three cases
      failed ureterorenoscopy due to technical difficulties. The overall success rate
      was 88.5% for FUR. CONCLUSION: FUR and LL are valuable minimally invasive
      techniques for the examination and treatment of pediatric upper urinary tract
      conditions. Preoperative stenting improves passage of the ureteroscope and with
      progressive miniaturization of instruments, the lower weight limit will decrease.

PMID- 20671849
TI  - Is ligation of hernial sac during orchiopexy mandatory?
AB  - AIM: Traditionally, ligation of hernial sac during orchiopexy is considered
      mandatory to prevent postoperative development of hernia. A prospective study was
      carried out to see if it is actually required based on the fact that any
      peritoneal defect closes within 24 hours by metamorphosis of the in situ
      mesodermal cells. METHODS: Fifty cases of undescended testis, age ranging from
      eight months to 12 years were enrolled. All of them underwent standard orchiopexy
      without ligation of the hernial sac. RESULTS: Follow up of all cases ranged
      between 1.5 years to three years. Not a single case was reported with evidence of
      hernia. CONCLUSIONS: It is unnecessary to ligate the hernial sac during
      orchiopexy.

PMID- 20671850
TI  - Bilateral giant juvenile fibroadenoma of breasts.
AB  - An 11-year-old girl with rapidly enlarging bilateral breast lumps is reported. It
      was diagnosed as a case of juvenile fibroadenoma following fine needle aspiration
      cytology and confirmed on histopathological examination of the excised specimens.

PMID- 20671851
TI  - Double aortic arches, esophageal atresia and tracheal compression.
AB  - We report a case of double aortic arch in a 12-month-old male infant well
      delineated on 64 slice computed tomography scan. It formed a complete vascular
      ring around the trachea compressing it. The symptoms resolved after surgical
      division of the ring.

PMID- 20671852
TI  - Embryogenesis of esophageal atresia: Is localized vascular accident a factor?
AB  - Several theories on embryogenesis of esophageal atresia have been proposed, none
      could explain the whole spectrum of this anomaly. We report a new variant of
      esophageal atresia in which the two blind pouches were joined by an atretic band.
      Histology of the atretic part showed groups of striated muscle arranged
      haphazardly without any lumen. The existing theories on etiology of esophageal
      atresia cannot explain this variant. However, localized vascular accident during
      intrauterine life resulting in disturbances in regional microcirculation could be
      a possible factor as demonstrated by Louw and Barnard in relation to jejunoileal
      atresia. This is contrary to the current understanding that disproportionate
      growth of the horizontal esophageal folds results in esophageal atresia.

PMID- 20671853
TI  - Urethral substitution with ileum in traumatic bladder neck-vagina fistula.
AB  - A five-year-old girl presented with post traumatic urinary incontinence secondary
      to rupture of the bladder neck into the vagina. Operative repair included a
      midline exposure with resection of the symphysis pubis, separation of the bladder
      neck from the vagina, repair of the torn bladder neck and urethral substitution
      with ileum. Normal continence and voiding was achieved.

PMID- 20671854
TI  - Bathing trunk nevus.

PMID- 20671855
TI  - A Case Report of Cerebral Venous Thrombosis in Polycythemia Vera Presenting with
      Intracranial and Spinal Subdural Hematoma.
AB  - Spinal subdural hematoma (SDH) is a rare condition and can be caused by several
      factors. Concomitant cranial and spinal SDH is even much less common. We present
      a 77-year-old male patient with lower back pain, paraparesis, and urinary
      retention following a sudden onset headache. Imaging revealed concomitant cranial
      and spinal SDH related to cerebral venous thrombosis (CVT) associated with
      hemorrhagic venous infarct. Laboratory examinations were consistent with
      polycythemia vera. There was no history of trauma and previous cranial surgery.
      Brain angiography did not reveal any evidence of arteriovenous fistula or
      vascular malformation. Since lower back pain occurred shortly after the headache
      and there was no other reasonable explanation for spinal hemorrhage, we suppose
      that the mechanism of spinal SDH is the migration of blood from the intracranial
      compartment. Therefore, this is the first report of concomitant spinal SDH and
      cerebral hemorrhage associated with CVT in a patient with myeloproliferative
      disease.

PMID- 20671856
TI  - High Levels of Copper, Zinc, Iron and Magnesium, but not Calcium, in the
      Cerebrospinal Fluid of Patients with Fahr's Disease.
AB  - Patients with marked calcification of the basal ganglia and cerebellum have
      traditionally been referred to as having Fahr's disease, but the nomenclature has
      been criticized for including heterogeneous etiology. We describe 3 patients with
      idiopathic bilateral striatopallidodentate calcinosis (IBSPDC). The patients were
      a 24-year-old man with mental deterioration, a 57-year-old man with parkinsonism
      and dementia, and a 76-year-old woman with dementia and mild parkinsonism. The
      former 2 patients showed severe calcification of the basal ganglia and
      cerebellum, and the latter patient showed severe calcification of the cerebellum.
      We found significantly increased levels of copper (Cu), zinc (Zn), iron (Fe) and
      magnesium (Mg), using inductively coupled plasma mass spectrometry in the CSF of
      all these 3 patients. The increased levels of Cu, Zn, Fe and Mg reflect the
      involvement of metabolism of several metals and/or metal-binding proteins during
      the progression of IBSPDC. More numerous patients with IBSPDC should be examined
      in other races to clarify the common mechanism of the disease and to investigate
      the specific treatment.

PMID- 20671857
TI  - Major Depressive Disorder Complicated with Spinocerebellar Ataxia: Report of 2
      Cases.
AB  - BACKGROUND: It is known that patients with spinocerebellar ataxia (SCA) tend to
      exhibit depressive symptoms. But the pathology of depressive symptoms complicated
      with SCA, including the reaction to the stress resulting from decreased motor
      function and central dysfunction due to neurodegeneration, is controversial and
      remains to be elucidated. To our knowledge, there have been hardly any reports on
      treatment methods of major depressive disorder (MDD) complicated with SCA. Case
      Reports: We report 2 cases in which selective serotonin reuptake inhibitors
      (SSRIs) were effective against MDD complicated with SCA. Interestingly, one of
      the patients developed the symptoms of spinocerebellar degeneration (SCD) during
      the course of the MDD, and the other patient developed the symptoms of MDD during
      the course of SCA, but complete remission of the MDD occurred in both cases. In
      our cases, the depressive symptoms may have been caused mainly by an abnormality
      of reversible neural transmission including serotonin transmission due to central
      dysfunction, and there is the unlikely possibility that the depressive symptoms
      are reactive to the stress due to decreased motor function, because the
      depressive symptoms decreased with SSRIs. CONCLUSION: Although cerebellar
      degeneration is irreversible in SCA patients, our cases suggest that MDD
      complicated with SCA may be reversible and treatable using antidepressants such
      as SSRIs with few adverse events. Therefore, it is important for neurologists to
      detect MDD complicated with SCA early and consult a psychiatrist in order to
      improve quality of life of SCA patients.

PMID- 20671858
TI  - Parry-Romberg Syndrome Associated with Localized Scleroderma.
AB  - Parry-Romberg syndrome is a rare neurocutaneous disorder of unknown origin. It is
      characterized by progressive facial hemiatrophy and frequently overlaps with a
      condition known as linear scleroderma 'en coup de sabre'. Neurological
      involvement is frequently described in these patients, including migraine, facial
      pain and epilepsy, which represent the commonest neurological conditions,
      sometimes associated with brain abnormalities ipsilaterally to the skin lesions.
      We present a case of Parry-Romberg syndrome with neurological involvement in a
      patient with diagnosed localized scleroderma (morphea).

PMID- 20671859
TI  - Cortical Vein Thrombosis as a Mimic for Isolated Cortical Subarachnoid Hemorrhage
      and Transient Ischemic Attack.
AB  - Isolated cortical subarachnoid hemorrhage is rare and poorly understood.
      Differential diagnoses and proposed pathophysiology vary widely and the
      diagnostic work-up for these patients who present with transient ischemic attack
      like episodes and characteristic imaging findings is still unclear. We report a
      case of isolated subarachnoid hemorrhage and transient neurologic deficits due to
      isolated cortical vein thrombosis that was not detected by noninvasive tests. A
      75-year-old woman with a history of a lobar intracerebral hemorrhage presented to
      the Academic Medical Center with sudden-onset transient left upper extremity
      weakness. Head CT showed a linear hyperdensity in the right precentral gyrus
      suggestive of isolated subarachnoid hemorrhage. MRI showed susceptibility in the
      corresponding area. CT angiogram and MRV showed no evidence of a venous
      thrombosis. The main outcome measures were results of computerized tomography and
      CT angiogram, magnetic resonance parenchymal and vascular imaging, angiography
      findings and clinical follow-up at 3 months. Cortical vein thrombosis was
      detected on conventional angiography. MRI was negative for microhemorrhages. The
      patient was anticoagulated and had no recurrences of her symptoms. We conclude
      that cortical vein thrombosis can present as isolated subarachnoid hemorrhage and
      transient ischemic attack-like episodes and may require angiography for
      definitive diagnosis.

PMID- 20671860
TI  - A Rare Malignant Triton Tumor.
AB  - Malignant peripheral nerve sheath tumor with rhabdomyoblastic differentiation,
      malignant triton tumor, has a rare incidence. We report such a case in a 40-year
      old male who presented with a mass over the buttock. He was a previously
      diagnosed case of neurofibroma in the same area. Histomorphology supported by
      immunostaining with S-100 protein confirmed the diagnosis. Malignant triton tumor
      has a poor prognosis owing to its aggressive biological behavior. The fact that
      the presence of this tumor in the buttock region is extremely rare has prompted
      the authors to report this case.

PMID- 20671861
TI  - Coma with Vertical Gaze Palsy: Relevance of Angio-CT in Acute Percheron Artery
      Syndrome.
AB  - BACKGROUND: A 63-year-old woman with chronic atrial fibrillation treated with
      warfarin was admitted to emergency for coma and complete vertical gaze palsy.
      Investigations: Brain CT and MRI, echo-colour Doppler sonography of the
      supraaortic vessels, angio-CT of the intracranial vessels, EEG, transesophageal
      echocardiogram, biohumoral tests. Brain CT and MRI scans showed bilateral
      thalamic lesions with involvement of the right midbrain; EEG showed a diffuse
      alpha rhythm prevalent on the posterior regions; echo-colour Doppler sonography
      of the supraaortic vessels showed marked reduction of blood flow in the right
      vertebral artery; angio-CT scans showed occlusion of the right vertebral artery
      and a significant filling defect of the first part of the right posterior
      cerebral artery (P1) from which the artery of Percheron arises. A follow-up angio
      CT showed a complete recanalization of P1. Diagnosis: Percheron artery syndrome.
      Treatment and Management: Aspirin, neurorehabilitation.

PMID- 20671862
TI  - Isolated Subarachnoidal Hemorrhage following Carotid Endarterectomy.
AB  - Cerebral hyperperfusion syndrome is a rare but well-described complication
      following carotid endarterectomy or stenting. Clinical signs are ipsilateral,
      throbbing, unilateral headache with nausea or vomiting, seizures, and
      neurological deficits, with or without intracerebral abnormalities on CT scan,
      such as brain edema or intracerebral hemorrhage. Subarachnoidal hemorrhage is
      rarely described especially if it occurs isolated. We describe a 74-year-old man
      with a history of high blood pressure, hypercholesterolemia, atrioventricular
      block with pacemaker, and ischemic cardiopathy with coronary bypass. He underwent
      right carotid endarterectomy for a 90% NASCET asymptomatic stenosis. Four days
      after surgery, he complained of unusual headaches with right, throbbing
      hemicrania. Nine days after surgery, he presented with left hemiplegia and a
      partial motor seizure. He had fluctuant altered consciousness, left hemiplegia,
      and left visual and sensory neglect. Brain CT showed right frontal subarachnoidal
      hemorrhage without parenchymal bleeding. Cerebral angiography found no cerebral
      aneurysm, no vascular malformation, but a vasospasm of the left middle cerebral
      artery. Transcranial Doppler confirmed this vasospasm. Evolution was favorable
      with no recurrence of seizures but with an improvement of the neurological
      deficits and vasospasm. Physicians should bear in mind this very rare
      complication of endarterectomy and immediately perform neuroimaging in case of
      unusual headache following endarterectomy or angioplasty.

PMID- 20671863
TI  - Arteriovenous Malformation in a Child with Extensive Involvement of the Mandible
      and Maxilla.
AB  - Arteriovenous malformation of both the maxilla and mandible in a pediatric
      patient is a very rare phenomenon that carries with it a high mortality rate.
      Arteriovenous malformations, sometimes known as simple vascular tumors, can be
      present from birth or acquired over time due to trauma, surgery, or any kind of
      vascular manipulation of an area of the body.

PMID- 20671864
TI  - Acute Ischemic Stroke in a Patient with a Native Valvular Strand.
AB  - Valvular strands are known to be a potential source of cardioembolism but the
      natural history of native valvular strands has not yet been fully outlined. We
      report a case of ischemic stroke in a patient with a native valvular strand of
      the aortic valve and the patient's clinical course. A previously healthy 21-year
      old man suffered acute cerebral infarction in the right posterior cerebral artery
      territory. On echocardiography, there was a strand-like, oscillating mass on the
      left coronary cusp of the aortic valve. The patient received 100 mg aspirin daily
      and the valvular strand was not found on subsequent transthoracic
      echocardiography performed 10 days after the first examination. Serial
      echocardiographic examinations have been performed since the stroke and failed to
      find any abnormality. The patient did not suffer a recurrent stroke over a 3-year
      follow-up period.

PMID- 20671865
TI  - The treatment of established non-union of the proximal humerus using the Polarus
      locking intramedullary nail.
AB  - INTRODUCTION: Non-union following fracture of the proximal humerus is not
      uncommon, particularly in the elderly. This can be associated with significant
      morbidity due to pain, instability and functional impairment. The Polarus device
      (Acumed) is a locked, antegrade intramedullary nail designed to stabilize
      displaced 2-, 3- and 4-part fractures of the proximal humerus. We report our
      experience with the Polarus nail for the treatment of established non-union of
      the proximal humerus. MATERIALS AND METHODS: A total of 7 Polarus nails were
      inserted for the treatment of non-union of the proximal humerus between June 2000
      and July 2007. Each fracture site was opened, debrided, stabilized with a Polarus
      nail and then grafted with autologous cancellous iliac crest bone. The time
      between injury and surgery ranged from 6 to 102 months. One patient had undergone
      previous fixation of her fracture using Rush intramedullary rods. All patients
      were females, and mean age at surgery was 63.6 years (range, 49-78 years). A
      retrospective review of notes and radiographs was carried out. Patients were
      reviewed at varying intervals postoperatively (range, 13-68 months) and assessed
      using the Constant shoulder-scoring system. RESULTS: All un-united fractures
      progressed to union. There were no wound complications and no postoperative nerve
      palsies. Functional outcome was good, even in those cases with a long interval
      between injury and surgery. The mean Constant score was 63 (range, 54-81).
      Migration of a single proximal locking screw was seen in 2 patients, and these
      screws required removal at 5 and 12 months, respectively, postoperatively.
      CONCLUSION: In our experience, a locked proximal humeral nail used in conjunction
      with autologous bone grafting is an excellent device for the treatment of
      proximal humerus non-unions.

PMID- 20671866
TI  - Functional outcome following proximal humeral interlocking system plating for
      displaced proximal humeral fractures.
AB  - AIM: To assess the functional outcome following internal fixation with the PHILOS
      (proximal humeral interlocking system) for displaced proximal humeral fractures.
      PATIENTS AND METHODS: We reviewed 30 consecutive patients treated surgically with
      the proximal humeral locking plate for a displaced proximal humeral fracture.
      Functional outcome was determined using the American Shoulder and Elbow Society
      (ASES) score and Constant Murley score. RESULTS: Average age of the patients was
      58 years (range, 19-92 years). The average overall ASES score was 66.5. The
      average overall Constant score was 57.5. CONCLUSION: Our results show that good
      fracture stability was achieved, and the functional outcome was very good in
      younger patients and it declined with increasing age. Early mobilization of the
      shoulder can be achieved without compromising fracture union.

PMID- 20671867
TI  - Early pullout of lateral row knotless anchor in rotator cuff repair.
AB  - Use of lateral row anchors in rotator cuff repair as a means of enhancing the
      strength of the repair; and improving footprint tendon contact, thus promoting
      healing, is becoming more popular in current arthroscopic practice. In our
      knowledge, failures of lateral row knotless anchors have not yet been reported.
      We present a case of double row rotator cuff repair using a Swivelock anchor
      (Arthrex) as a lateral row anchor that failed two weeks after surgery.

PMID- 20671868
TI  - A modified surgical technique for reconstruction of an acute acromioclavicular
      joint dislocation.
AB  - We report a modified surgical technique for reconstruction of coracoclavicular
      and acromioclavicular ligaments after acute dislocation of acromioclavicular
      joint using suture anchors. We have repaired 3 consecutive type III
      acromioclavicular dislocations with good results. This technique is simple and
      safe and allows anatomical reconstruction of the ligaments in acute dislocations.

PMID- 20671869
TI  - Nonunion of a posterior glenoid rim fracture leading to posterior subluxation.

PMID- 20671870
TI  - A rare combination of an axillary artery and brachial plexus injury due to a
      proximal humeral fracture.

PMID- 20671871
TI  - Do we need to test blood donors for sickle cell anaemia?

PMID- 20671872
TI  - Umbilical cord blood collection, storage and use: ethical issues.

PMID- 20671873
TI  - Prothrombin complex concentrates: an update.

PMID- 20671874
TI  - Evaluation of cardiovascular risk in blood donors: results of the CARDIORISK
      study in the Parma Transfusion Service.
AB  - BACKGROUND: Cardiovascular disease, which is one of the main causes of mortality
      in industrialised countries, is ever increasingly the focus of prevention. In
      this study, called "Cardiorisk", we evaluated cardiovascular risk in the
      population of blood donors at the Service of Immunohaematology and Transfusion
      Medicine in Parma. PATIENTS AND METHODS: Between January 2007 and December 2008,
      6,172 consecutive blood donors (aged 35-65 years) were enrolled in this project
      which entailed calculating each subject's cardiovascular risk score, based on an
      evaluation of both unalterable risk factors (age and gender) and modifiable risk
      factors (total cholesterol, HDL, LDL, triglycerides, glycaemia, smoking,
      hypertension) as well as anti-hypertensive and/or cholesterol-lowering therapy.
      RESULTS: Of the 6,172 donors enrolled in the study, 5,039 (81.7%) had a low
      cardiovascular risk (score from 0-10), 774 (12.5%) had a moderate cardiovascular
      risk (score from 11-19) and 359 (5.8%) donors had a high cardiovascular risk
      (score from 20-28). CONCLUSIONS: In our opinion, the calculation of
      cardiovascular risk is an important instrument for preventive medicine in blood
      donors.

PMID- 20671875
TI  - Sequence-specific primers for MNS blood group genotyping.
AB  - BACKGROUND: Various techniques of genotyping the MNSs blood group have been
      described, but none of them enables the complete detection of all MNS antigens.
      MATERIALS AND METHODS: Blood samples were obtained from blood donors. Primers
      were created using the published DNA sequences for glycophorins A and B.
      Genotyping was performed using polymerase chain reaction sequence-specific
      primers (PCR-SSP). RESULTS: A total of seven primers were found to specifically
      amplify the most common MNS antigens. The use of these primers has enabled us to
      correctly genotype all blood samples tested so far (n=116). DISCUSSION:
      Specifically created primers enable genotyping of the MNS antigens in a single
      PCR-SSP run. The method is reliable, easy to perform, and can be used in routine
      practice.

PMID- 20671877
TI  - The procedures for authorisation and accreditation of Transfusion Structures and
      blood donation centres: what are the requisites? The experience of the
      Transfusion Service and AVIS blood donation centres in Ravenna.
AB  - BACKGROUND: The system of accreditation of Italian transfusion structures
      (Transfusion Services and blood donation centres, these latter being managed by
      voluntary associations) guarantees the National Health Service that the service
      provided to citizens, patients and donors who use these structures, is correctly
      authorised, meets further, additional requisites relative to the quality of
      health care, and that these are documented and controlled during a formal audit.
      MATERIALS AND METHODS: We present here the experience gained, in the period 2007
      2009, by the Transfusion Service of the local health authority of Ravenna and of
      the AVIS blood donation centres in the Province of Ravenna (Italy). These blood
      donation centres are managed in the context of a stipulated arrangement in which
      agreement was reached concerning not only the purposes, but also the quality
      requirements of the blood product collection, the operative methods, and the
      indicators and surveillance of non-conformities, in order to monitor and improve
      the blood supply system in the province. RESULTS: Our data show that, over time,
      there was a improvement in the distribution of collection of whole blood across
      the days of the week and better training of staff, as demonstrated by a reduction
      in non-conformities. Analysis of the data encouraged the identification of a new
      organisation with computerisation of the blood donation centres and their
      progressive merging. CONCLUSIONS: There are numerous, precise legislative and
      technical indications to guarantee the quality of performances in transfusion
      medicine, from the collection of blood to its allocation. These indications
      constitute a qualified basis for the development of accreditation models whose
      final validation is the duty of specifically designated regional and national
      institutions. The procedure for obtaining accreditation, planned and carried out
      uniformly by the Transfusion Service and the voluntary association's donation
      centres was an occasion for professional staff to improve the quality of the
      services delivered. Collectively, these aspects have increased transparency and
      improved the system of blood supply in the province of Ravenna.

PMID- 20671876
TI  - Distribution of antibodies to Salmonella in the sera of blood donors in the south
      western region of Nigeria.
AB  - BACKGROUND: There are currently no reports of a multicentre assessment of the
      presence of antibodies to Salmonella in donated blood in Nigeria. MATERIALS AND
      METHODS: Blood specimens from blood donors presenting at six selected public
      blood collection centres in the south-western region of Nigeria were analysed for
      the presence of Salmonella antibodies. RESULTS: Out of the 200 specimen analysed,
      106 (53%) were found to be Widal-positive with a minimum titre of 160. Among the
      positive cases, reactivity was most common to S. typhi (D) antigens (48.6%). The
      most frequently recorded titre of reactive specimens (i.e., the modal titre) was
      160, with 71 donors (35.5%) of the total sample population from the different
      centres reacting at this level. Thirty-one donors had elevated titres of = 320
      and nine donors had a titre of 640. The percentages of Widal-positive cases among
      donors with A positive and O positive blood groups were 58.7% and 64.2%,
      respectively; the percentage of Widal-positive cases was lowest among B positive
      blood donors (26.7%). The p-value for these differences (p<0.05) shows that blood
      group has a statistically significant impact on Widal reaction in donors.
      CONCLUSION.: This study confirms that salmonellosis is endemic in Nigeria and
      that many of our blood donors may be Salmonella carriers. This study also
      revealed a positive association between blood groups and typhoid fever.

PMID- 20671878
TI  - Epidemiology of human immunodeficiency virus infection in blood donations in
      Europe and Italy.
AB  - BACKGROUND: The safety of blood with regards to transmission of infectious
      diseases is guaranteed by European laws that regulate both the selection of
      donors through pre-donation questionnaires and serological screening. However,
      variability in the epidemiology of human immunodeficiency virus (HIV) infection
      in different countries and some differences in the selection of donors can
      influence the efficacy (with regards to the safety of blood) of these processes.
      In this study we compared the prevalence of HIV in blood donations in the three
      macro-areas of Europe and in various western European countries, analysed the
      criteria of selection and rewarding of donors in western European countries, and
      studied the trend in the prevalence of HIV in Italy from to 1995 and 2006.
      METHODS: European data were derived from the European Centre for the Surveillance
      of HIV; Italian data were obtained from the Transfusion-Transmitted Infections
      Surveillance System and National and Regional Register of blood and plasma. The
      information on eligibility criteria and rewarding offered to donors was derived
      from international sources. RESULTS: The prevalence of HIV in blood donations was
      highest in eastern Europe, followed by central Europe and western Europe. Among
      the western European countries, Spain, Italy and Israel had the highest
      prevalences; the prevalence was noted to be higher in countries which did not
      offer any rewarding to the donor. In Italy the prevalence of HIV was 3.8 cases
      per 100,000 donations in 2006 and increased between 1995 and 2006, both among
      donations from repeat donors and first time donors. CONCLUSIONS: The data
      highlight the need to continue improving the selection of donors and the coverage
      of the surveillance systems for HIV infection in transfusion services.

PMID- 20671879
TI  - The Mirasol Pathogen Reduction Technology system and quality of platelets stored
      in platelet additive solution.
AB  - BACKGROUND: The Mirasol Pathogen Reduction Technology system for platelets and
      plasma uses riboflavin and UV light to introduce irreparable lesions into nucleic
      acids thereby inhibiting pathogen and white blood cell replication and reducing
      the load of infectious pathogens. The aim of the present study was to evaluate
      low plasma buffy coat platelet concentrates obtained from the OrbiSac System and
      to examine the effects on the development of platelet storage lesion during
      storage in platelet additive solution. MATERIAL AND METHODS: Twenty buffy coat
      platelet concentrates were generated by pooling five individual units using the
      OrbiSac System. Riboflavin was added during the final pooling step, and the units
      were exposed to UV light. The bag was removed after the target energy of 6.24
      J/mL had been delivered and 150 mL of platelet additive solution were added prior
      to storage. Platelet quality was assessed by pH, swirl, CD62P expression, lactate
      dehydrogenase, lactate production and glucose consumption rates over 7 days of
      storage. RESULTS: Buffy coat platelet concentrates generated on the OrbiSac
      contained an average 3.5 +/- 0.6 x 10(11) platelets at a concentration of 2976+/-
      406 x 10(6)/mL. After addition of 150 mL platelet additive solution the storage
      concentration was 1043 +/- 148x 10(6)/mL. Values obtained for pH, lactate
      production and glucose consumption rates were all within the limits of previously
      established correlations between in vitro cell quality and in vivo performance of
      Pathogen Reduction Technology-treated platelets in plasma. DISCUSSION: In vitro
      studies show that OrbiSac-derived platelets treated with the Mirasol Pathogen
      Reduction Technology system preserve adequate function, which would indicate
      acceptable in vitro viability.

PMID- 20671880
TI  - Factor V Leiden in Chioggia: a prevalence study in patients with venous
      thrombosis, their blood relatives and the general population.

PMID- 20671881
TI  - Clinical improvement induced by rituximab in two cases of type II mixed
      cryoglobulinaemia syndrome unresponsive to conventional treatments.

PMID- 20671882
TI  - An unusual case of a spurious, transfusion-acquired haemoglobin S.

PMID- 20671883
TI  - Rituximab for managing relapsing or refractory patients with idiopathic
      thrombotic thrombocytopenic purpura--haemolytic uraemic syndrome.

PMID- 20671884
TI  - Bone marrow necrosis in sickle cell anaemia.

PMID- 20671887
TI  - Mistakes to avoid in the implementation of community mental health care.

PMID- 20671888
TI  - WPA guidance on steps, obstacles and mistakes to avoid in the implementation of
      community mental health care.
AB  - This paper provides guidance on the steps, obstacles and mistakes to avoid in the
      implementation of community mental health care. The document is intended to be of
      practical use and interest to psychiatrists worldwide regarding the development
      of community mental health care for adults with mental illness. The main
      recommendations are presented in relation to: the need for coordinated policies,
      plans and programmes, the requirement to scale up services for whole populations,
      the importance of promoting community awareness about mental illness to increase
      levels of help-seeking, the need to establish effective financial and budgetary
      provisions to directly support services provided in the community. The paper
      concludes by setting out a series of lessons learned from the accumulated
      practice of community mental health care to date worldwide, with a particular
      focus on the social and governmental measures that are required at the national
      level, the key steps to take in the organization of the local mental health
      system, lessons learned by professionals and practitioners, and how to most
      effectively harness the experience of users, families, and other advocates.

PMID- 20671889
TI  - Successful cognitive and emotional aging.
AB  - We review the definitions, determinants, and ways of enhancing successful
      cognitive and emotional aging. Objective definitions of successful aging based on
      physical health emphasize outcomes including freedom from disability and disease,
      whereas subjective definitions center on well-being, social connectedness, and
      adaptation. Most older people do not meet objective criteria for successful
      aging, while a majority meet the subjective criteria. Older people with severe
      mental illness are not excluded from successful aging. The determinants of
      successful aging include complex interactions of lifestyle behaviors and social
      environment with genes. Depression interferes with nearly all determinants of
      successful aging. Evidence-based means of enhancing successful aging include
      calorie restriction, physical exercise, cognitive stimulation, social support,
      and optimization of stress. Future directions for successful aging research and
      implications for geriatric psychiatry are discussed.

PMID- 20671890
TI  - Problematic Internet use: an overview.
AB  - There is wide agreement that the Internet can serve as a tool that enhances well
      being. It is more difficult, however, to find consensus around the issue of
      problematic Internet use. That may be in part because scientific investigation
      has lagged far behind technological advances and media attention. The diagnostic
      schemas that have been proposed since 1996, and the screening tools that have
      been developed, stress similarities with substance use, impulse control
      disorders, and obsessive-compulsive disorder. Prevalence figures vary as a
      function of the diagnostic definition used, the age group studied, and whether
      the surveys were conducted online. Studies suggest high comorbidity rates with
      mood disorders and, among younger individuals, attention-deficit/hyperactivity
      disorder. Treatment should address any comorbid conditions present, as those may
      be causing, or exacerbating, problematic Internet use. Interventions that may
      specifically target problematic Internet use include cognitive behavioral therapy
      and selective serotonin reuptake inhibitors, but detailed guidelines must await
      further studies. For a medium that has so radically changed how we conduct our
      lives, the Internet's effects on our psychology remain understudied. More
      research is needed into the pathophysiology, epidemiology, natural course, and
      treatment of problematic Internet use. In addition, the more subtle psychological
      changes, such as disinhibition, that seem to characterize people's online
      behavior also deserve attention, even if they cannot be seen as necessarily
      pathological.

PMID- 20671891
TI  - Internet addiction over the decade: a personal look back.

PMID- 20671892
TI  - Problematic Internet use: a distinct disorder, a manifestation of an underlying
      psychopathology, or a troublesome behaviour?

PMID- 20671893
TI  - Problematic Internet use and the diagnostic journey.

PMID- 20671895
TI  - The Internet: every good thing has a dark side.

PMID- 20671894
TI  - Problematic use in context.

PMID- 20671896
TI  - Problematic Internet use: is it more compulsory than rewarding or mood driven?

PMID- 20671897
TI  - Internet addiction: ongoing research in Asia.

PMID- 20671898
TI  - Exploring the apparent absence of psychosis amongst the Borana pastoralist
      community of Southern Ethiopia. A mixed method follow-up study.
AB  - There are few reports of the prevalence of psychotic disorders among isolated
      population groups. Where present, variations in prevalence estimates raise
      questions about the validity of methods of case ascertainment in such settings.
      In a previous population-based survey of the Borana pastoralist community in
      Ethiopia using the Composite International Diagnostic Interview, no cases of
      schizophrenia were identified. In order to further explore this finding and
      investigate how serious mental disorder is conceptualized, we conducted focus
      group discussions with key members of the Borana pastoralist community.
      Subsequently, focus group participants were used as key informants to identify
      cases with possible psychotic disorder, based on their conceptualization. Cases
      identified by key informants were interviewed by a trained psychiatrist using the
      Schedules for Clinical Assessment in Neuropsychiatry (SCAN), to confirm presence
      of disorder. Focus group discussions were subjected to thematic analysis. The
      incongruity between local and psychiatric concepts lay mainly in the fact that
      key informants described characteristics of marata ("madness") in terms of overt
      behavioural symptoms. Following the focus group discussions, participants
      identified eight individuals with schizophrenia and 13 with a psychotic mood
      disorder, confirmed through SCAN interview. Studies of psychotic disorders in
      such communities are likely to benefit from combining structured interviews with
      the key informant method.

PMID- 20671899
TI  - The role of anxious and hyperthymic temperaments in mental disorders: a national
      epidemiologic study.
AB  - Temperament has been demonstrated clinically to be linked to mental disorders. We
      aimed to determine the possible role of temperament in mental disorders in a
      national epidemiologic study. A nationally representative sample of adults
      (n=1320) was administered the Lebanese-Arabic version of the Temperament
      Evaluation of the Memphis, Pisa, Paris and San Diego Autoquestionnaire (TEMPS-A),
      and the Arabic CIDI 3.0, as part of the LEBANON study. The association among
      temperaments and DSM-IV mood, anxiety, and impulse control disorders was
      assessed. The anxious temperament was shown to be a robust predictor of most
      disorders, especially within the anxiety and depressive clusters. The hyperthymic
      temperament had a uniquely protective effect on most mental disorders, with the
      exception of separation anxiety, bipolar, substance abuse and impulse control
      disorders. These effects were moderated by age and education. Temperaments,
      previously largely neglected in epidemiologic studies, could play a major role in
      the origin of mental disorders.

PMID- 20671900
TI  - The effectiveness of child and adolescent psychiatric treatments in a
      naturalistic outpatient setting.
AB  - Data concerning the effectiveness of naturalistic treatments (treatment-as-usual)
      in child and adolescent psychiatric (CAP) services are scarce. The purpose of
      this prospective observational study was to examine the effectiveness of CAP
      treatments in a naturalistic outpatient setting. Three hundred six patients
      (attention-deficit/hyperactivity disorder, ADHD, n=94; conduct disorder, CD,
      n=57; anxiety disorder, AD, n=53; depressive disorder, DD, n=38; other diagnostic
      categories, n=64), from nine child and adolescent psychiatric practices in
      Germany, were evaluated. Treatment effects were compared between patients who
      received frequent treatment and patients who only participated in diagnostics and
      short interventions. Since randomization was not feasible, propensity score
      analysis methods were used. Regarding the total sample, no significant treatment
      effects were found. However, a subgroup analysis of the four most frequent
      disorders (ADHD, CD, AD, DD) showed small to moderate treatment effects in
      patients with ADHD and AD. In CD and DD subgroups, no significant treatment
      effects could be found. "Real-world" CAP outpatient treatment seems to produce
      significant effects for ADHD and AD, but not for CD and DD. Compared to efficacy
      studies, our results show that naturalistic treatment might be better than
      expected.

PMID- 20671901
TI  - Integration of mental health into primary care in Kenya.
AB  - Integration of mental health into primary care is essential in Kenya, where there
      are only 75 psychiatrists for 38 million population, of whom 21 are in the
      universities and 28 in private practice. A partnership between the Ministry of
      Health, the Kenya Psychiatric Association and the World Health Organization (WHO)
      Collaborating Centre, Institute of Psychiatry, Kings College London was funded by
      Nuffield Foundation to train 3,000 of the 5,000 primary health care staff in the
      public health system across Kenya, using a sustainable general health system
      approach. The content of training was closely aligned to the generic tasks of the
      health workers. The training delivery was integrated into the normal national
      training delivery system, and accompanied by capacity building courses for
      district and provincial level staff to encourage the inclusion of mental health
      in the district and provincial annual operational plans, and to promote the
      coordination and supervision of mental health services in primary care by
      district psychiatric nurses and district public health nurses. The project
      trained 41 trainers, who have so far trained 1671 primary care staff, achieving a
      mean change in knowledge score of 42% to 77%. Qualitative observations of
      subsequent clinical practice have demonstrated improvements in assessment,
      diagnosis, management, record keeping, medicine supply, intersectoral liaison and
      public education. Around 200 supervisors (psychiatrists, psychiatric nurses and
      district public health nurses) have also been trained. The project experience may
      be useful for other countries also wishing to conduct similar sustainable
      training and supervision programmes.

PMID- 20671902
TI  - Orienting psychiatrists to working in emergencies: a WPA-WHO workshop.

PMID- 20671903
TI  - Should "risk syndrome for psychosis" be included as a diagnosis in DSM-V?

PMID- 20671904
TI  - Lack of association between duration of untreated psychosis and outcome in an
      Indian cohort.

PMID- 20671905
TI  - The 15th world congress of psychiatry (Buenos Aires, september 18-22, 2011).

PMID- 20671906
TI  - WPA Project on Partnerships for Best Practices in Working with Service Users and
      Carers.

PMID- 20671908
TI  - Investigation of Balance Function Using Dynamic Posturography under Electrical
      Acoustic Stimulation in Cochlear Implant Recipients.
AB  - Introduction. The purpose of the present study is to investigate the effect of
      electrical-acoustic stimulation on vestibular function in CI patients by using
      the EquiTest and to help answer the question of whether electrically stimulating
      the inner ear using a cochlear implant influences the balance system in any way.
      Material and Methods. A test population (n = 50) was selected at random from
      among the cochlear implant recipients. Dynamic posturography (using the EquiTest)
      was performed with the device switched off an switched on. Results. In summary,
      it can be said that an activated cochlear implant affects the function of the
      vestibular system and may, to an extent, even lead to a stabilization of balance
      function under the static conditions of dynamic posturography, but nevertheless
      also to a significant destabilization. Significant improvements in vestibular
      function were seen mainly in equilibrium scores under conditions 4 and 5, the
      composite equilibrium score, and the vestibular components as revealed by sensory
      analysis. Conclusions. Only under the static conditions are significantly poorer
      scores achieved when stimulation is applied. It may be that the explanation for
      any symptoms of dizziness lies precisely in the fact that they occur in
      supposedly noncritical situations, since, when the cochlear implant makes
      increased demands on the balance system, induced disturbances can be centrally
      suppressed.

PMID- 20671907
TI  - Shaping the archaeal cell envelope.
AB  - Although archaea have a similar cellular organization as other prokaryotes, the
      lipid composition of their membranes and their cell surface is unique. Here we
      discuss recent developments in our understanding of the archaeal protein
      secretion mechanisms, the assembly of macromolecular cell surface structures, and
      the release of S-layer-coated vesicles from the archaeal membrane.

PMID- 20671909
TI  - Retrospective illumination correction of retinal images.
AB  - A method for correction of nonhomogenous illumination based on optimization of
      parameters of B-spline shading model with respect to Shannon's entropy is
      presented. The evaluation of Shannon's entropy is based on Parzen windowing
      method (Mangin, 2000) with the spline-based shading model. This allows us to
      express the derivatives of the entropy criterion analytically, which enables
      efficient use of gradient-based optimization algorithms. Seven different gradient
      and nongradient-based optimization algorithms were initially tested on a set of
      40 simulated retinal images, generated by a model of the respective image
      acquisition system. Among the tested optimizers, the gradient-based optimizer
      with varying step has shown to have the fastest convergence while providing the
      best precision. The final algorithm proved to be able of suppressing
      approximately 70% of the artificially introduced non-homogenous illumination. To
      assess the practical utility of the method, it was qualitatively tested on a set
      of 336 real retinal images; it proved the ability of eliminating the illumination
      inhomogeneity substantially in most of cases. The application field of this
      method is especially in preprocessing of retinal images, as preparation for
      reliable segmentation or registration.

PMID- 20671910
TI  - Combined piggyback technique and cavoportal hemitransposition for liver
      transplant.
AB  - Portal Vein thrombosis (PVT) increases the difficulty of liver transplant;
      however, it is not an absolute contraindication. Cavoportal hemitransposition
      (CPH) is an option for patients with complete PVT and no alternative collateral
      vein. Our center often performs the piggyback technique for the hepatic vein
      reconstruction, which allows for great access to the recipient vena cava in
      patients with known complete PVT that may need a CPH preformed to successfully
      restore flow to the portal system of the donor liver. We describe the use of the
      piggy-back technique to prepare the vena cava for possible CPH in patients with
      known complete PVT.

PMID- 20671911
TI  - PPAR-alpha Contributes to the Anti-Inflammatory Activity of Verbascoside in a
      Model of Inflammatory Bowel Disease in Mice.
AB  - The previous results suggest that peroxisome proliferator-activated receptor
      alpha (PPAR)-alpha, an intracellular transcription factor activated by fatty
      acids, plays a role in control of inflammation. There is persuasive
      epidemiological and experimental evidence that dietary polyphenols have anti
      inflammatory activity. In this regard, it has been demonstrated that verbascoside
      (VB) functions as intracellular radical scavenger and reduces the microscopic and
      macroscopic signs of experimental colitis. With the aim to characterize the role
      of PPAR-alpha in VB-mediated anti-inflammatory activity, we tested the efficacy
      of VB in an experimental model of inflammatory bowel disease induced by
      dinitrobenzene sulfonic acid, comparing mice lacking PPAR-alpha (PPAR-alphaKO)
      with wild type (WT) mice. Results indicate that VB-mediated anti-inflammatory
      activity is weakened in PPAR-alphaKO mice, compared to WT controls, especially in
      the inhibition of neutrophil infiltration, intestinal permeability and colon
      injury. These results indicate that PPAR-alpha can contribute to the anti
      inflammatory activity of VB in inflammatory bowel disease.

PMID- 20671912
TI  - Interleukin-6 contributes to age-related alteration of cytokine production by
      macrophages.
AB  - Here, we studied in vitro cytokine production by splenic macrophages obtained
      from young and aged BALB/c wild type (WT) and IL-6 knockout (IL-6 KO) mice.
      Relative to macrophages obtained from young WT mice given lipopolysaccharide
      (LPS), those from aged WT mice had decreased production of proinflammatory
      cytokines. In contrast, when compared to macrophages from young IL-6 KO mice, LPS
      stimulation yielded higher levels of these cytokines by cells from aged IL-6 KO
      mice. Aging or IL-6 deficiency did not affected the percentage of F4/80(+)
      macrophages, or the surface expression of Toll-like receptor 4 (TLR4) and
      components of the IL-6 receptor. Overall, our results indicate that IL-6 plays a
      role in regulating the age-related defects in macrophages through alteration of
      proinflammatory cytokines, adding to the complexity of IL-6-mediated impairment
      of immune cell function with increasing age.

PMID- 20671913
TI  - Claudin family of proteins and cancer: an overview.
AB  - Tight junctions are the apical cell-cell adhesion that regulate paracellular
      permeability and are critical for epithelial cell polarity. Molecular
      architecture of tight junction has been studied extensively, which has confirmed
      that claudin family of proteins is integral component of tight junction. Loss of
      cell-cell adhesion is central to the cellular transformation and acquisition of
      metastatic potential; however, the role of claudin family of proteins play in a
      series of pathophysiological events, including human carcinoma development, is
      only now beginning to be understood. Several claudin mouse knockout models have
      been generated and the diversity of phenotypes observed clearly demonstrates
      their important roles in the maintenance of tissue integrity in various organs
      and suggest that claudins also participate in cellular contexts other than tight
      junctions. The mechanisms of claudin regulation and their exact roles in normal
      physiology and disease are being elucidated, but much work remains to be done. In
      this review, we have discussed the conceptual framework concerning claudins and
      their potential implication in cancer. We predict that next several years will
      likely witness a boom in our understanding of the potential role of claudins in
      the regulation of tumorigenesis, which may, in turn, provide new approaches for
      the targeted therapy.

PMID- 20671915
TI  - Herpes simplex type 1 encephalitis restricted to the brainstem in a pediatric
      patient.
AB  - Herpes simplex encephalitis is a potentially fatal infection of central nervous
      system that typically involves frontal and temporal lobes. Occasionally, it
      presents an extratemporal involvement and in rarer cases, it is limited to the
      brainstem. We describe a case of an adolescent who presented with fever, sore
      throat, and vertigo. Clinical picture evolved to lethargy, tetraparesis,
      consciousness impairment, and respiratory failure. MRI showed lesions restricted
      to the brainstem. PCR of CSF was positive for herpes simplex type 1.

PMID- 20671914
TI  - Oxidative stress and DNA methylation in prostate cancer.
AB  - The protective effects of fruits, vegetables, and other foods on prostate cancer
      may be due to their antioxidant properties. An imbalance in the oxidative
      stress/antioxidant status is observed in prostate cancer patients. Genome
      oxidative damage in prostate cancer patients is associated with higher lipid
      peroxidation and lower antioxidant levels. Oxygen radicals are associated with
      different steps of carcinogenesis, including structural DNA damage, epigenetic
      changes, and protein and lipid alterations. Epigenetics affects genetic
      regulation, cellular differentiation, embryology, aging, cancer, and other
      diseases. DNA methylation is perhaps the most extensively studied epigenetic
      modification, which plays an important role in the regulation of gene expression
      and chromatin architecture, in association with histone modification and other
      chromatin-associated proteins. This review will provide a broad overview of the
      interplay of oxidative stress and DNA methylation, DNA methylation changes in
      regulation of gene expression, lifestyle changes for prostate cancer prevention,
      DNA methylation as biomarkers for prostate cancer, methods for detection of
      methylation, and clinical application of DNA methylation inhibitors for
      epigenetic therapy.

PMID- 20671916
TI  - Type I IL-1 receptor (IL-1RI) as potential new therapeutic target for bronchial
      asthma.
AB  - The IL-1R/TLR family has been receiving considerable attention as potential
      regulators of inflammation through their ability to act as either activators or
      suppressors of inflammation. Asthma is a chronic inflammatory disease
      characterized by airway hyperresponsiveness, allergic inflammation, elevated
      serum total, allergen-specific IgE levels, and increased Th2 cytokine production.
      The discovery that the IL-1RI-IL-1 and ST2-IL-33 pathways are crucial for
      allergic inflammation has raised interest in these receptors as potential targets
      for developing new therapeutic strategies for bronchial asthma. This paper
      discusses the current use of neutralizing mAb or soluble receptor constructs to
      deplete cytokines, the use of neutralizing mAb or recombinant receptor
      antagonists to block cytokine receptors, and gene therapy from experimental
      studies in asthma. Targeting IL-1RI-IL-1 as well as ST2-IL-33 pathways may
      promise a disease-modifying approach in the future.

PMID- 20671918
TI  - Study on the Imprinting Status of Insulin-Like Growth Factor II (IGF-II) Gene in
      Villus during 6-10 Gestational Weeks.
AB  - Objective. To compare the difference of imprinting status of insulin-like growth
      factor II (IGF-II) gene in villus between normal embryo development group and
      abnormal embryo development group and to investigate the relationship between
      karyotype and the imprinting status of IGF-II gene. Methods. A total of 85
      pregnant women with singleton pregnancy were divided into two groups: one with
      abnormal embryo development (n = 38) and the other with normal embryo development
      (n = 47). Apa I polymorphism of IGF-II gene in chorionic villus was assayed with
      reverse transcriptase polymerase chain reaction (RT-PCR) and restriction fragment
      length polymorphism (RFLP). The relationship between chromosomal abnormal
      karyotype and IGF-II gene imprinting status was analyzed by primary cell culture
      and G-banding chromosomal karyotype analysis. Results. IGF-II imprinting loss
      rate was higher in the abnormal embryo development group than the normal embryo
      development group (44.7% versus 31.6%), but without significant difference (P >
      .05). The percentage of abnormal chromosomes of chorionic villus in the abnormal
      embryo development group was 42.5%, in which IGF-II imprinting loss rate reached
      64.7%. No abnormal karyotypes were found in the normal embryo development group.
      However, there was significant difference in IGF-II imprinting loss rate between
      two groups (P > .05). Conclusion. During weeks 6-10 of gestation, abnormal
      embryonic development is correlated with chromosomal abnormalities. The
      imprinting status of IGF-II gene played important roles in embryonic development,
      and imprinting loss might be related to chromosomal abnormalities.

PMID- 20671917
TI  - Extracellular matrix proteins and tumor angiogenesis.
AB  - Tumor development is a complex process that relies on interaction and
      communication between a number of cellular compartments. Much of the mass of a
      solid tumor is comprised of the stroma which is richly invested with
      extracellular matrix. Within this matrix are a host of matricellular proteins
      that regulate the expression and function of a myriad of proteins that regulate
      tumorigenic processes. One of the processes that is vital to tumor growth and
      progression is angiogenesis, or the formation of new blood vessels from
      preexisting vasculature. Within the extracellular matrix are structural proteins,
      a host of proteases, and resident pro- and antiangiogenic factors that control
      tumor angiogenesis in a tightly regulated fashion. This paper discusses the role
      that the extracellular matrix and ECM proteins play in the regulation of tumor
      angiogenesis.

PMID- 20671919
TI  - Pulmonary alveolar microlithiasis: a case report with emphasis on imaging
      findings.
AB  - Pulmonary alveolar microlithiasis (PAM) is a rare disease characterized by the
      presence of small calculi in the alveolar space. The authors report a case of a
      21-year-old man with a 2-year history of shortness of breath on exertion and dry
      cough. Physical examination was altered only for crackles at auscultation.
      Pulmonary function revealed a mild restrictive ventilatory defect and the chest
      radiograph demonstrated paracardiac confluence of dense micronodular infiltrate.
      High-resolution CT scan revealed diffuse ground glass attenuation and septal
      thickening, more pronounced in lower pulmonary regions, with calcifications along
      the interlobar septa and subpleural regions. A transbronchial lung biopsy
      confirmed the diagnosis of PAM.

PMID- 20671920
TI  - Temporomandibular joint bone tissue resorption in patients with early rheumatoid
      arthritis can be predicted by joint crepitus and plasma glutamate level.
AB  - The aim was to investigate whether bone tissue resorption in early RA is related
      to crepitus of the temporomandibular joint (TMJ) and systemic levels of
      inflammatory mediators and markers and sex steroid hormones. Twentynine women and
      18 men with recently diagnosed RA were examined for TMJ bone erosions with
      computerized tomography and TMJ crepitus was assessed. Blood samples were
      analyzed for glutamate, 5-HT, TNF, IL-1beta, IL-6, VEGF, inflammatory markers,
      and estradiol, progesterone and testosterone. The TMJ erosion score was
      positively correlated to glutamate, and TMJ crepitus where crepitus, glutamate
      and ESR explained 40% of the variation in the bone erosion score. In the patients
      without crepitus, bone erosion score was positively correlated to glutamate,
      which was not the case in the patients with crepitus. In conclusion, the results
      of this study show that TMJ bone tissue resorption can be predicted by TMJ
      crepitus and glutamate in early RA.

PMID- 20671922
TI  - Sclerosing mesenteritis as a cause of abdominal mass and discomfort in an elderly
      patient: a case report and literature review.
AB  - Sclerosing mesenteritis is a rare benign process that involves inflammation, fat
      necrosis, and fibrosis of the mesentery. The disease poses great diagnostic
      challenge due to its nonspecific clinical and diagnostic findings. We report the
      case of a 75-year-old man who presented with vague abdominal discomfort
      associated with an intra-abdominal mass. With suspicion of a bowel carcinoid
      tumor on computed tomography scans, the patient underwent diagnostic laparoscopy.
      A diagnosis of sclerosing mesenteritis was made on histological examination. The
      patient's symptoms responded to a combination of immunosuppressive drugs, with no
      interval change in the size of the mass on radiological examination after fifteen
      months.

PMID- 20671923
TI  - Ozone and ozonated oils in skin diseases: a review.
AB  - Although orthodox medicine has provided a variety of topical anti-infective
      agents, some of them have become scarcely effective owing to antibiotic- and
      chemotherapeutic-resistant pathogens. For more than a century, ozone has been
      known to be an excellent disinfectant that nevertheless had to be used with
      caution for its oxidizing properties. Only during the last decade it has been
      learned how to tame its great reactivity by precisely dosing its concentration
      and permanently incorporating the gas into triglycerides where gaseous ozone
      chemically reacts with unsaturated substrates leading to therapeutically active
      ozonated derivatives. Today the stability and efficacy of the ozonated oils have
      been already demonstrated, but owing to a plethora of commercial products, the
      present paper aims to analyze these derivatives suggesting the strategy to obtain
      products with the best characteristics.

PMID- 20671921
TI  - Immunomodulatory effects of dsRNA and its potential as vaccine adjuvant.
AB  - dsRNA can be detected by pattern recognition receptors, for example, TLR3, MDA-5,
      NLRP3 to induce proinflammatory cytokines responsible for innate/adaptive
      immunity. Recognized by endosomal TLR3 in myeloid DCs (mDCs), dsRNA can activate
      mDCs into mature antigen presenting cells (mAPCs) which in turn present antigen
      epitopes with MHC-I molecules to naive T cells. Coadministration of protein and
      synthetic dsRNA analogues can elicit an antigen-specific Th1-polarized immune
      response which stimulates the CD8+ CTL response and possibly dampen Th17
      response. Synthetic dsRNA analogues have been tested as vaccine adjuvant against
      viral infections in animal models. However, a dsRNA receptor, TLR3 can be
      expressed in tumor cells while other members of TLR family, for example, TLR4 and
      TLR2 have been shown to promote tumor progression, metastasis, and
      chemoresistance. Thus, the promising potential of dsRNA analogues as a tumor
      therapeutic vaccine adjuvant should be evaluated cautiously.

PMID- 20671924
TI  - Comparison of two mice strains, A/J and C57BL/6, in caspase-1 activity and IL
      1beta secretion of macrophage to Mycobacterium leprae infection.
AB  - A/J mice were found to have amino acid differences in Naip5, one of the NOD-like
      receptors (NLRs) involved in the cytosolic recognition of pathogen-associated
      molecular patterns and one of the adaptor proteins for caspase-1 activation. This
      defect was associated with a susceptibility to Legionella infection, suggesting
      an important role for Naip5 in the immune response also to other intracellular
      pathogens, such as Mycobacterium leprae. In this study, the immune responses of
      macrophages from A/J mice against M. leprae were compared to those of macrophages
      from C57BL/6 mice. Infection with M. leprae induced high levels of TNF-alpha
      production and NF-kappaB activation in A/J and C57BL/6 macrophages. Caspase-1
      activation and IL-1beta secretion were also induced in both macrophages. However,
      macrophages from A/J mice exhibited reduced caspase-1 activation and IL-1beta
      secretion compared to C57BL/6 macrophages. These results suggest that NLR family
      proteins may have a role in the innate immune response to M. leprae.

PMID- 20671925
TI  - Loop Electrosurgical Excisional Procedure (LEEP) Done for Discrepancy: Does the
      Time from HGSIL Affect Pathologic Grade of CIN in LEEP Specimen?
AB  - Objective. When pathologic discrepancy arises between high-grade cytology on
      Papanicolaou (Pap) smear and low-grade histology on cervical biopsy, Loop
      Electrosurgical Excisional Procedure (LEEP) is one management alternative. Our
      objective was to determine whether the time from initial HGSIL Pap to LEEP
      affects the pathologic grade of the LEEP specimen. Study Design. We performed a
      retrospective case-control study identifying LEEPs performed for discrepancy over
      a 10-year period (1997-2007). 121 subjects were separated into two groups based
      on LEEP pathology (</=CIN 1 and CIN 2,3) and compared using chi(2). Results. Of
      the 121 LEEP specimens, 67 (55.4%) had CIN 2,3. CIN 2,3 was more often discovered
      when LEEP was performed within 3 months of the HGSIL Pap smear versus after 5
      months (55.2% versus 16.4%, P = .096). Conclusion. Women undergoing LEEP for
      discrepancy >5 months from their HGSIL Pap demonstrated a trend toward less CIN
      2,3 on LEEP pathology.

PMID- 20671926
TI  - Promoter variant of PIK3C3 is associated with autoimmunity against Ro and Sm
      epitopes in African-American lupus patients.
AB  - The PIK3C3 locus was implicated in case-case genome-wide association study of
      systemic lupus erythematosus (SLE) which we had performed to detect genes
      associated with autoantibodies and serum interferon-alpha (IFN-alpha). Herein, we
      examine a PIK3C3 promoter variant (rs3813065/-442 C/T) in an independent
      multiancestral cohort of 478 SLE cases and 522 controls. rs3813065 C was strongly
      associated with the simultaneous presence of both anti-Ro and anti-Sm antibodies
      in African-American patients [OR = 2.24 (1.34-3.73), P = 2.0 x 10(-3)]. This
      autoantibody profile was associated with higher serum IFN-alpha (P = 7.6 x 10(
      6)). In the HapMap Yoruba population, rs3813065 was associated with differential
      expression of ERAP2 (P = 2.0 x 10(-5)), which encodes an enzyme involved in MHC
      class I peptide processing. Thus, rs3813065 C is associated with a particular
      autoantibody profile and altered expression of an MHC peptide processing enzyme,
      suggesting that this variant modulates serologic autoimmunity in African-American
      SLE patients.

PMID- 20671927
TI  - Cytokines and growth factors stimulate hyaluronan production: role of hyaluronan
      in epithelial to mesenchymal-like transition in non-small cell lung cancer.
AB  - In this study, we investigated the role of hyaluronan (HA) in non-small cell lung
      cancer (NSCLC) since close association between HA level and malignancy has been
      reported. HA is an abundant extracellular matrix component and its synthesis is
      regulated by growth factors and cytokines that include epidermal growth factor
      (EGF) and interleukin-1beta (IL-1beta). We showed that treatment with recombinant
      EGF and IL-1beta, alone or in combination with TGF-beta, was able to stimulate HA
      production in lung adenocarcinoma cell line A549. TGF-beta/IL-1beta treatment
      induced epithelial to mesenchymal-like phenotype transition (EMT), changing cell
      morphology and expression of vimentin and E-cadherin. We also overexpressed
      hyaluronan synthase-3 (HAS3) in epithelial lung adenocarcinoma cell line H358,
      resulting in induced HA expression, EMT phenotype, enhanced MMP9 and MMP2
      activities and increased invasion. Furthermore, adding exogenous HA to A549 cells
      and inducing HA H358 cells resulted in increased resistance to epidermal growth
      factor receptor (EGFR) inhibitor, Iressa. Together, these results suggest that
      elevated HA production is able to induce EMT and increase resistance to Iressa in
      NSCLC. Therefore, regulation of HA level in NSCLC may be a new target for
      therapeutic intervention.

PMID- 20671928
TI  - Leptin administration downregulates the increased expression levels of genes
      related to oxidative stress and inflammation in the skeletal muscle of ob/ob
      mice.
AB  - Obese leptin-deficient ob/ob mice exhibit a low-grade chronic inflammation
      together with a low muscle mass. Our aim was to analyze the changes in muscle
      expression levels of genes related to oxidative stress and inflammatory responses
      in leptin deficiency and to identify the effect of in vivo leptin administration.
      Ob/ob mice were divided in three groups as follows: control ob/ob, leptin-treated
      ob/ob (1 mg/kg/d) and leptin pair-fed ob/ob mice. Gastrocnemius weight was lower
      in control ob/ob than in wild type mice (P < .01) exhibiting an increase after
      leptin treatment compared to control and pair-fed (P < .01) ob/ob animals.
      Thiobarbituric acid reactive substances, markers of oxidative stress, were higher
      in serum (P < .01) and gastrocnemius (P = .05) of control ob/ob than in wild type
      mice and were significantly decreased (P < .01) by leptin treatment. Leptin
      deficiency altered the expression of 1,546 genes, while leptin treatment modified
      the regulation of 1,127 genes with 86 of them being involved in oxidative stress,
      immune defense and inflammatory response. Leptin administration decreased the
      high expression of Crybb1, Hspb3, Hspb7, Mt4, Cat, Rbm9, Serpinc1 and Serpinb1a
      observed in control ob/ob mice, indicating that it improves inflammation and
      muscle loss.

PMID- 20671929
TI  - The role of adipose tissue and adipokines in obesity-related inflammatory
      diseases.
AB  - Obesity is an energy-rich condition associated with overnutrition, which impairs
      systemic metabolic homeostasis and elicits stress. It also activates an
      inflammatory process in metabolically active sites, such as white adipose tissue,
      liver, and immune cells. As consequence, increased circulating levels of
      proinflammatory cytokines, hormone-like molecules, and other inflammatory markers
      are induced. This determines a chronic active inflammatory condition, associated
      with the development of the obesity-related inflammatory diseases. This paper
      describes the role of adipose tissue and the biological effects of many
      adipokines in these diseases.

PMID- 20671930
TI  - The structure and function of serum opacity factor: a unique streptococcal
      virulence determinant that targets high-density lipoproteins.
AB  - Serum opacity factor (SOF) is a virulence determinant expressed by a variety of
      streptococcal and staphylococcal species including both human and animal
      pathogens. SOF derives its name from its ability to opacify serum where it
      targets and disrupts the structure of high-density lipoproteins resulting in
      formation of large lipid vesicles that cause the serum to become cloudy. SOF is a
      multifunctional protein and in addition to its opacification activity, it binds
      to a number of host proteins that mediate adhesion of streptococci to host cells,
      and it plays a role in resistance to phagocytosis in human blood. This article
      will provide an overview of the structure and function of SOF, its role in the
      pathogenesis of streptococcal infections, its vaccine potential, its prevalence
      and distribution in bacteria, and the molecular mechanism whereby SOF opacifies
      serum and how an understanding of this mechanism may lead to therapies for
      reducing high-cholesterol concentrations in blood, a major risk factor for
      cardiovascular disease.

PMID- 20671931
TI  - Cytokine overproduction, T-cell activation, and defective T-regulatory functions
      promote nephritis in systemic lupus erythematosus.
AB  - Lupus nephritis (LN) occurs in more than one-third of patients with systemic
      lupus erythematosus. Its pathogenesis is mostly attributable to the glomerular
      deposition of immune complexes and overproduction of T helper- (Th-) 1 cytokines.
      In this context, the high glomerular expression of IL-12 and IL-18 exerts a major
      pathogenetic role. These cytokines are locally produced by both macrophages and
      dendritic cells (DCs) which attract other inflammatory cells leading to
      maintenance of the kidney inflammation. However, other populations including T
      cells and B-cells are integral for the development and worsening of renal damage.
      T-cells include many pathogenetic subsets, and the activation of Th-17 in keeping
      with defective T-regulatory (Treg) cell function regards as further event
      contributing to the glomerular damage. These populations also activate B-cells to
      produce nephritogenic auto-antibodies. Thus, LN includes a complex pathogenetic
      mechanism that involves different players and the evaluation of their activity
      may provide an effective tool for monitoring the onset of the disease.

PMID- 20671932
TI  - Multiple-locus variable-number tandem repeat analysis of Vibrio cholerae in
      comparison with pulsed field gel electrophoresis and virulotyping.
AB  - Molecular analysis of Malaysian Vibrio cholerae was carried out using a multiple
      locus variable-number tandem repeat analysis (MLVA) assay based on 7 loci of V.
      cholerae. The discriminatory ability of the assay was compared with pulsed-field
      gel electrophoresis (PFGE) using 43 Malaysian V. cholerae isolated from various
      sources. In addition, the virulotypes of the strains were determined. Based on
      MLVA, 38 allelic profiles were obtained (F = 0.63) while PFGE generated 35
      pulsotypes (F = 0.71). Simpson's index of diversity for different VNTR loci
      ranged from 0.59 to 0.92. The combined loci increased the discriminatory index to
      0.99 which was comparable with PFGE (D = 0.99). Most of the environmental non
      O1/non-O139 strains harbored rtxA, rstR, toxR, and hlyA only, and the virulotype
      of this serogroup was significantly different (P < .01) from
      clinical/environmental O1 and environmental O139 strains. In conclusion, the MLVA
      assay developed in this study was a useful genotyping tool with comparable
      discriminatory power with PFGE. In addition, the combination of the two
      approaches can further distinguish the strains from different sources and
      geographical regions of isolation.

PMID- 20671933
TI  - Protein-protein interaction changes in an archaeal light-signal transduction.
AB  - Negative phototaxis in Natronomonas pharaonis is initiated by transient
      interaction changes between photoreceptor and transducer. pharaonis
      phoborhodopsin (ppR; also called pharaonis sensory rhodopsin II, psR-II) and the
      cognate transducer protein, pHtrII, form a tight 2 : 2 complex in the
      unphotolyzed state, and the interaction is somehow altered during the photocycle
      of ppR. We have studied the signal transduction mechanism in the ppR/pHtrII
      system by means of low-temperature Fourier-transform infrared (FTIR)
      spectroscopy. In the paper, spectral comparison in the absence and presence of
      pHtrII provided fruitful information in atomic details, where vibrational bands
      were identified by the use of isotope-labeling and site-directed mutagenesis.
      From these studies, we established the two pathways of light-signal conversion
      from the receptor to the transducer; (i) from Lys205 (retinal) of ppR to Asn74 of
      pHtrII through Thr204 and Tyr199, and (ii) from Lys205 of ppR to the cytoplasmic
      loop region of pHtrII that links Gly83.

PMID- 20671935
TI  - Chronobiology and chronomics: detecting and applying the cycles of nature.
AB  - We monitor our streets to prevent assault and rodents to develop drugs, but not
      those for whom the drugs are intended. It took over half a century to begin to
      monitor blood sugar values in patients with insulin-dependent diabetes.
      Monitoring blood pressure is equally timely and technically feasible for
      individual home- and website-based personalised care. It also serves basic
      science and someday perhaps the management of societal illnesses.

PMID- 20671934
TI  - Genetic dissection of the AZF regions of the human Y chromosome: thriller or
      filler for male (in)fertility?
AB  - The azoospermia factor (AZF) regions consist of three genetic domains in the long
      arm of the human Y chromosome referred to as AZFa, AZFb and AZFc. These are of
      importance for male fertility since they are home to genes required for
      spermatogenesis. In this paper a comprehensive analysis of AZF structure and gene
      content will be undertaken. Particular care will be given to the molecular
      mechanisms underlying the spermatogenic impairment phenotypes associated to AZF
      deletions. Analysis of the 14 different AZF genes or gene families argues for the
      existence of functional asymmetries between the determinants; while some are
      prominent players in spermatogenesis, others seem to modulate more subtly the
      program. In this regard, evidence supporting the notion that DDX3Y, KDM5D,
      RBMY1A1, DAZ, and CDY represent key AZF spermatogenic determinants will be
      discussed.

PMID- 20671937
TI  - Role of infection in neurologic and psychiatric diseases.

PMID- 20671936
TI  - Review of Neurosurgical Fluorescence Imaging Methodologies.
AB  - Fluorescence imaging in neurosurgery has a long historical development, with
      several different biomarkers and biochemical agents being used, and several
      technological approaches. This review focuses on the different contrast agents,
      summarizing endogenous fluorescence, exogenously stimulated fluorescence and
      exogenous contrast agents, and then on tools used for imaging. It ends with a
      summary of key clinical trials that lead to consensus studies. The practical
      utility of protoporphyrin IX (PpIX) as stimulated by administration of delta
      aminolevulinic acid (ALA) has had substantial pilot clinical studies and basic
      science research completed. Recently multi-center clinical trials using PpIx
      fluorescence to guide resection have shown efficacy for improved short term
      survival. Exogenous agents are being developed and tested pre-clinically, and
      hopefully hold the potential for long term survival benefit if they provide
      additional capabilities for resection of micro-invasive disease or certain tumor
      sub-types that do not produce PpIX or help delineate low grade tumors. The range
      of technologies used for measurement and imaging ranges widely, with most
      clinical trials being carried out with either point probes or modified surgical
      microscopes. At this point in time, optimized probe approaches are showing
      efficacy in clinical trials, and fully commercialized imaging systems are
      emerging, which will clearly help lead to adoption into neurosurgical practice.

PMID- 20671938
TI  - Effects of supplemental exogenous emulsifier on performance, nutrient metabolism,
      and serum lipid profile in broiler chickens.
AB  - The effects of an exogenous emulsifier, glyceryl polyethylene glycol ricinoleate,
      on performance and carcass traits of broiler chickens were assessed. The
      emulsifier was added to the diet at dose rates of 0 (control), 1 (E1) and 2 (E2)
      % of added fat (saturated palm oil). Live weight gain (P < .07) and feed
      conversion ratio (P < .05) in 39 days were higher in the E1 dietary group. Gain:
      ME intake and gain: protein intake during the grower phase improved quadratically
      (P < .05). Gross carcass traits were not affected. Body fat content and fat
      accretion increased (P < .05) and liver fat content decreased (P < .05) linearly
      with the level of emulsifier in diet. Fat excretion decreased (P < .001) leading
      to increased ileal fat digestibility (P < .06) in the E1 group (quadratic
      response). Metabolizable intake of N (P < .1) and fat (P < .05) increased
      quadratically due to supplementation of emulsifier in diet. Metabolism of trace
      elements and serum lipid profiles were not affected. The study revealed that
      supplementation of exogenous emulsifiers in diets containing moderate quantities
      of added vegetable fats may substantially improve broiler performance.

PMID- 20671940
TI  - Preimplantation genetic screening: an effective testing for infertile and
      repeated miscarriage patients?
AB  - Aneuploidy in pregnancy is known to increase with advanced maternal age (AMA) and
      associate with repeated implantation failure (RIF), and repeated miscarriage
      (RM). Preimplantation genetic screening (PGS) has been introduced into clinical
      practice, screening, and eliminating aneuploidy embryos, which can improve the
      chance of conceptions for infertility cases with poor prognosis. These patients
      are a good target group to assess the possible benefit of aneuploidy screening.
      Although practiced widely throughout the world, there still exist some doubts
      about the efficacy of this technique. Recent randomized trials were not as
      desirable as we expected, suggesting that PGS needs to be reconsidered. The aim
      of this review is to discuss the efficacy of PGS.

PMID- 20671941
TI  - Serum Interleukin-4 and Total Immunoglobulin E in Nonatopic Alopecia Areata
      Patients and HLA-DRB1 Typing.
AB  - Background. Interleukin-4 (IL-4), a Th(2) cytokine, can stimulate immunoglobulin
      E (IgE) transcription. No previous studies evaluated the genetic mechanisms in
      nonatopic AA patients with elevated serum IgE. Objective. To compare serum IL-4
      and total IgE levels between Egyptian nonatopic AA patients and healthy subjects
      and to investigate a possible relation to HLA-DRB1 alleles. Results. Serum IL-4
      and total IgE were measured by ELISA in 40 controls and 54 nonatopic AA patients.
      Patients' HLA-DRB1 typing by sequence specific oligonucleotide probe technique
      was compared to normal Egyptian population. We found significantly elevated serum
      IL-4 and total IgE in AA patients (particularly alopecia universalis, AU, and
      chronic patients) (P < .01). HLA-DRB1*11 is a general susceptibility/chronicity
      allele. DRB1*13 is a protective allele. DRB1*01 and DRB1*07 are linked to
      chronicity. Localized AA showed decreased DRB1*03 and DRB1*07. Extensive forms
      showed increased DRB1*08 and decreased DRB1*04. Elevated IL4 and IgE were
      observed in patients with DRB1*07 and DRB1*11 not DRB1*04. Conclusion. Serum IL-4
      and IgE are elevated in nonatopic AA patients, particularly AU and chronic
      disease. Relevant susceptibility, chronicity, and severity HLADRB1 alleles may
      have a role in determining type, magnitude, and duration of immune response in AA
      favouring increased IL4 and IgE.

PMID- 20671939
TI  - Advances in cellular therapy for the treatment of thyroid cancer.
AB  - Up to now, there are no curative therapies available for the subset of
      metastasized undifferentiated/anaplastic thyroid carcinomas. This review
      describes the possible use of immunocompetent cells which may help to restore the
      antitumor immune recognition for treating an existing tumor or preventing its
      recurrence. The most prominent experimental strategy is the use of dendritic
      cells (DCs) which are highly potent in presenting tumor antigens. Activated DCs
      subsequently migrate to draining lymph nodes where they present antigens to naive
      lymphocytes and induce cytotoxic T cells (CTL). Alternatively to DC therapy,
      adoptive cell transfer may be performed by either using natural killer cells or
      ex vivo maturated CTLs. Within this review article we will focus on recent
      advances in the understanding of anti-tumor immune responses, for example, in
      thyroid carcinomas including the advances which have been made for the
      identification of potential tumor antigens in thyroid malignancies.

PMID- 20671942
TI  - Every wheeze does not merit a puffer! Case of an overnight cure of chronic
      asthma.
AB  - The peril of incorrect diagnostic labelling is highlighted by this case of acute
      respiratory distress caused by a retrosternal recurrent goitre. An initial
      clinical diagnosis which cannot be fully validated on investigation with
      unexpected or poor response to treatment should prompt consideration and
      investigation for an alternative explanation.

PMID- 20671943
TI  - Why do parents with toddlers store poisonous products safely?
AB  - Unintentional poisoning is a major cause of nonfatal injuries in children aged 0
      24 months. Associations between self-reported habits on the child safe storage of
      medication and cleaning products and family, and psychosocial factors were
      assessed, using a model based on the Protection Motivation Theory. By identifying
      correlates of safety behavior in this manner, more insight in factors which
      influence this behavior is obtained. Health promotion activities in order to
      promote safety behavior should address these factors in order to increase the
      effectiveness of the health message. Data were gathered from a cross-sectional
      survey using self-administered questionnaires, mailed to a population sample of
      2470 parents with toddlers. The results indicate that the promotion of safe
      storage of medication and cleaning products should address the family situation,
      personal cognitive factors as well as social factors. Interventions should
      particularly focus on parents' self-efficacy of storing poisonous products in a
      child safe manner and on the vulnerability of their child in their home
      concerning an unintentional poisoning incident.

PMID- 20671944
TI  - Temporal Variations among Invasive Pneumococcal Disease Serotypes in Children and
      Adults in Germany (1992-2008).
AB  - Nationwide surveillance of invasive pneumococcal disease has been conducted in
      Germany since 1992. From 1992 to 2008, a total of 12,137 isolates from invasive
      pneumococcal disease were collected. Data on serotypes were available for 9,394
      invasive isolates. The leading serotypes were serotypes 14 (16.5%), 3 (8.0%), 7F
      (7.6%), 1 (7.3%), and 23F (6.0%). Variations in serotype distribution over the
      years are particularly extensive, especially concerning serotype 14 (min 7.4%,
      max 33.5%) with the highest percentages among the isolates serotyped from around
      1997 to 2006. Serotypes 1 and 7F increased over the last decade. No increase was
      observed concerning serotype 19A. Higher pneumococcal conjugate vaccine coverages
      were observed among children (7v, 57.3%; 10v, 72.8%; 13v, 83.5%) than among
      adults (7v, 39.9%; 10v, 55.5%; 13v, 73.5%). The temporal variations in serotype
      distribution have to be kept in mind when interpreting vaccine coverages reported
      in epidemiological studies.

PMID- 20671945
TI  - The Passage of S100B from Brain to Blood Is Not Specifically Related to the Blood
      Brain Barrier Integrity.
AB  - Following brain injury, S100B is released from damaged astrocytes but also yields
      repair mechanisms. We measured S100B in the cerebrospinal fluid (CSF) and serum
      (Cobas e411 electrochemiluminescence assay, Roche) longitudinally in a large
      cohort of patients treated with a ventricular drainage following traumatic brain
      injury (TBI) or subarachnoid hemorrhage (SAH). Statistical analysis was performed
      with SPSS software applying the Mann-Whitney rank sum test or chi-test where
      appropriate. S100B in CSF and serum was significantly increased following TBI (n
      = 71) and SAH (n = 185) for at least one week following injury. High S100B levels
      in CSF and serum were inconsistent associated with outcome. The passage of S100B
      from CSF to blood (100( *)serum(S100B)/CSF(S100B)) was significantly decreased
      although the albumin quotient suggested an "open" blood-CSF barrier. Events
      possibly interfering with the BBB did not affect the S100B passage (P = .591). In
      conclusion, we could not confirm S100B measurements to reliably predict outcome,
      and a compromised blood-CSF barrier did not affect the passage of S100B from CSF
      to serum.

PMID- 20671946
TI  - Navajo coal combustion and respiratory health near Shiprock, New Mexico.
AB  - Indoor air pollution has been identified as a major risk factor for acute and
      chronic respiratory diseases throughout the world. In the sovereign Navajo
      Nation, an American Indian reservation located in the Four Corners area of the
      USA, people burn coal in their homes for heat. To explore whether/how indoor coal
      combustion might contribute to poor respiratory health of residents, this study
      examined respiratory health data, identified household risk factors such as fuel
      and stove type and use, analyzed samples of locally used coal, and measured and
      characterized fine particulate airborne matter inside selected homes. In twenty
      five percent of homes surveyed coal was burned in stoves not designed for that
      fuel, and indoor air quality was frequently found to be of a level to raise
      concerns. The average winter 24-hour PM2.5 concentration in 20 homes was 36.0
      MUg/m3. This is the first time that PM2.5 has been quantified and characterized
      inside Navajo reservation residents' homes.

PMID- 20671947
TI  - Effects of Endogenous PPAR Agonist Nitro-Oleic Acid on Metabolic Syndrome in
      Obese Zucker Rats.
AB  - Nitroalkene derivatives of nitro-oleic acid (OA-NO(2)) are endogenous lipid
      products with novel signaling properties, particularly the activation of PPARs.
      The goal of this proposal was to examine the therapeutic potential of this OA
      NO(2) in treatment of obesity and obesity-related conditions in obese Zucker
      rats. The animals were randomly divided to receive OA-NO(2), oleic acid (OA),
      both at 7.5 mug/kg/d, or vehicle ethanol via osmotic mini-pumps for 2 weeks.
      Following OA-NO(2) treatment, food intake was decreased as early as the first day
      and this effect appeared to persist throughout the experimental period. At day
      14, body weight gain was significantly reduced by OA-NO(2) treatment. This
      treatment significantly reduced plasma triglyceride and almost normalized plasma
      free fatty acid and significantly increased plasma high-density lipid (HDL). The
      plasma TBARS and proteinuria were paralelly decreased. In contrast, none of these
      parameters were affected by OA treatment. After 14 days of OA-NO(2) treatment,
      hematocrit, a surrogate of fluid retention associated with PPARgamma agonists,
      remained unchanged. Together, these data demonstrated that OA-NO(2) may offer an
      effective and safe therapeutic intervention for obesity and obesity-related
      conditions.

PMID- 20671948
TI  - Possible implication of local immune response in Darier's disease: an
      immunohistochemical characterization of lesional inflammatory infiltrate.
AB  - Cell-mediated immunity is considered to be normal in Darier's Disease (DD), an
      inherited skin disorder complicated by skin infections. To date, there are no
      investigations on the local inflammatory infiltrate in DD skin lesions. In this
      immunohistochemical study we characterized and quantified it, making comparisons
      with two other inflammatory skin disorders, that is, pemphigus vulgaris (PV) and
      lichen ruber planus (LRP), and with the normal skin (NSk). We found a significant
      (P < .05) decrease of CD1a+ Langerhans cells (LCs) in DD, compared to PV, LRP,
      and NSk, and of CD123+ plasmacytoid dendritic cells (pDCs), compared to PV and
      LRP. We hypothesize that the genetic damage of keratinocytes might result in a
      loss of some subsets of dendritic cells and, consequently, in an impaired local
      immune response, which might worsen the infections that inevitably occur in this
      disease.

PMID- 20671949
TI  - Laugier-hunziker syndrome: an uncommon cause of oral pigmentation and a review of
      the literature.
AB  - Laugier-Hunziker syndrome is a rare benign condition characterized by diffuse
      oral hyperpigmentation associated with pigmentation of the nails. The syndrome
      must be included in the differential diagnosis of diffuse oral pigmentation to
      exclude other conditions with systemic implications. We describe a 43-year-old
      white woman with the clinical and histological features of Laugier-Hunziker
      syndrome associated with toenail pigmentation. The correct clinical
      identification avoids the need for detailed investigations and treatment. We also
      review the potential causes of oral pigmentation.

PMID- 20671950
TI  - Xanthomatous hypophysitis mimicking a pituitary adenoma: case report and review
      of the literature.
AB  - Background. Hypophysitis is an inflammatory disease of the pituitary gland that
      may mimic pituitary tumors clinically and radiologically. Case Description. We
      report a case of a xanthomatous hypophysitis initially diagnosed as pituitary
      adenoma. A 31-year-old woman presented with headache, diabetes insipidus, and
      amenorrhea. A head CT scan showed no intrasellar changes, while an MRI scan
      showed a sellar cystic mass. An endocrinological work up revealed mild
      hypocortisolism and diabetes insipidus (DI). Transsphenoidal surgery was
      performed. The intraoperative histological examination suggested a pituitary
      adenoma. The removed tissue showed central necrosis surrounded by accumulation of
      foamy cells and xanthomatous epithelioid cells. The patient made an uneventful
      postoperative recovery, Nevertheless, DI persisted and the adenohypophysis
      hypofunction did not recover. Conclusion. We describe an unusual inflammatory
      lesion of the pituitary gland mimicking an adenoma. A high level of clinical
      suspicion of inflammatory disorders is necessary for correct diagnosis and
      optimal management.

PMID- 20671951
TI  - Investigation on the Interactions of NiCR and NiCR-2H with DNA.
AB  - We report here a biophysical and biochemical approach to determine the
      differences in interactions of NiCR and NiCR-2H with DNA. Our goal is to
      determine whether such interactions are responsible for the recently observed
      differences in their cytotoxicity toward MCF-7 cancer cells. Viscosity
      measurement and fluorescence displacement titration indicated that both NiCR and
      NiCR-2H bind weakly to duplex DNA in the grooves. The coordination of NiCR-2H
      with the N-7 of 2'-deoxyguanosine 5'-monophosphate (5'-dGMP) is stronger than
      that of NiCR as determined by (1)H NMR. NiCR-2H, like NiCR, can selectively
      oxidize guanines present in distinctive DNA structures (e.g., bulges), and
      notably, NiCR-2H oxidizes guanines more efficiently than NiCR. In addition, UV
      and (1)H NMR studies revealed that NiCR is oxidized into NiCR-2H in the presence
      of KHSO(5) at low molar ratios with respect to NiCR (</=4).

PMID- 20671952
TI  - Levels of Circulating TIMP-2 and MMP2-TIMP2 Complex Are Decreased in Squamous
      Cervical Carcinoma.
AB  - Background. The role of matrix metalloproteinase-2 and -9 (MMP-2, MMP-9) in
      matrix degradation and metastasis has been described in various tumors. Their
      action is inhibited by their natural tissue inhibitor molecules TIMP-1 and -2.
      Methods. The study population consisted of 12 squamous cervical carcinoma
      patients and 27 healthy volunteer control patients. MMP-9, MMP-2-TIMP-2 complex,
      TIMP-1, and TIMP-2 were analyzed from serum samples using enzyme-linked
      immunoassay (ELISA). Results. The mean levels of serum TIMP-2 and of MMP-2-TIMP-2
      complex were higher in healthy controls compared to patients with a malignant
      tumor. Serum TIMP-2 values decreased significantly from healthy controls (median
      323 mug/l, range 305-342 mug/l) to malignant (median 136 mug/l, range 120-151
      mug/l) squamous cervical carcinoma patients (P < .000). Also, serum proMMP2-TIMP2
      complex values decreased from control patients to squamous cervical carcinoma
      patients (P < .006). Conclusion. This paper shows that the levels of circulating
      TIMP-2 and that of MMP-2-TIMP-2 complex are lower in squamous cervical carcinoma
      patients than in healthy women.

PMID- 20671953
TI  - Inhibition of methylglyoxal-mediated protein modification in glyoxalase I
      overexpressing mouse lenses.
AB  - Objective. Here we tested the role of Glo I in the prevention of advanced
      glycation end product (AGE) formation in transgenic mouse lenses. Methods. A
      transgenic animal line that expressed high levels of human Glo I in the lens was
      developed from the C57B6 mouse strain. The role of Glo I in the inhibition of MGO
      AGE formation was tested in organ-cultured lenses. Results. Organ culture of Wt
      and Glo I lenses with 5 mM D, L-glyceraldehyde (GLD) enhanced MGO by 29-fold and
      17-fold in Wt lenses and Glo I lenses, respectively. Argpyrimidine levels were
      192 +/- 73 pmoles/mg protein, and hydroimidazolone levels were 22 +/- 0.7
      units/mug protein in GLD-incubated Wt lenses. In Glo I lenses, formation of AGEs
      was significantly inhibited; the argpyrimidine levels were 82 +/- 18 pmoles/mg
      protein, and the HI levels were 2.6 +/- 2.3 units/mug protein. Incubation of Wt
      lens proteins with 5 mM ribose for 7 days resulted in the formation of
      pentosidine. However, the levels were substantially higher in Glo I lens proteins
      incubated with ribose. Conclusion. Our study provides direct evidence that Glo I
      activity plays an important role in the regulation of AGE synthesis in the lens;
      while Glo I activity blocks the formation of MGO-AGEs, it might promote the
      formation of sugar-derived AGEs.

PMID- 20671954
TI  - Phosphorylation and methylation of proteasomal proteins of the haloarcheon
      Haloferax volcanii.
AB  - Proteasomes are composed of 20S core particles (CPs) of alpha- and beta-type
      subunits that associate with regulatory particle AAA ATPases such as the
      proteasome-activating nucleotidase (PAN) complexes of archaea. In this study, the
      roles and additional sites of post-translational modification of proteasomes were
      investigated using the archaeon Haloferax volcanii as a model. Indicative of
      phosphorylation, phosphatase-sensitive isoforms of alpha1 and alpha2 were
      detected by 2-DE immunoblot. To map these and other potential sites of post
      translational modification, proteasomes were purified and analyzed by tandem mass
      spectrometry (MS/MS). Using this approach, several phosphosites were mapped
      including alpha1 Thr147, alpha2 Thr13/Ser14 and PAN-A Ser340. Multiple
      methylation sites were also mapped to alpha1, thus, revealing a new type of
      proteasomal modification. Probing the biological role of alpha1 and PAN-A
      phosphorylation by site-directed mutagenesis revealed dominant negative
      phenotypes for cell viability and/or pigmentation for alpha1 variants including
      Thr147Ala, Thr158Ala and Ser58Ala. An H. volcanii Rio1p Ser/Thr kinase homolog
      was purified and shown to catalyze autophosphorylation and phosphotransfer to
      alpha1. The alpha1 variants in Thr and Ser residues that displayed dominant
      negative phenotypes were significantly reduced in their ability to accept
      phosphoryl groups from Rio1p, thus, providing an important link between cell
      physiology and proteasomal phosphorylation.

PMID- 20671955
TI  - Timing of imaging after d-luciferin injection affects the longitudinal assessment
      of tumor growth using in vivo bioluminescence imaging.
AB  - The peak signal or the signal at a predetermined, fixed time point after D
      luciferin injection may be used for the quantitative analysis of in vivo
      bioluminescence imaging. We repeatedly performed sequential bioluminescence
      imaging after subcutaneous injection of D-luciferin in mice bearing subcutaneous
      tumors. The peak time in each measurement became shorter early after cell
      inoculation, presumably due to gradual establishment of intratumoral vasculature,
      and reached a plateau of about 10 min on day 10. Although the correlation between
      the signal at a fixed time point and the peak signal was high, the signal at 5 or
      10 min normalized for the peak signal was lower for earlier days, which caused
      overestimation of tumor growth. The time course of the signals after D-luciferin
      injection may vary with time after cell inoculation, and this variation should be
      considered when determining the imaging protocol for quantitative bioluminescence
      tumor monitoring.

PMID- 20671956
TI  - When a doctor becomes a patient with a mystery illness: a case report.
AB  - Symptoms presenting as mental disorders may represent epileptic discharges,
      especially from the temporal lobe. Both mental and somatic symptoms are common in
      temporal lobe epilepsy, which may confuse doctors, leading to extensive medical
      examinations and tests, false diagnoses, and ineffective treatment. Also, the
      episodic nature and variety of symptoms between as well as in individual cases
      hinder correct diagnosis. Since epileptic discharges may be visible on EEG only
      during an epileptic fit-and may need highly specialized equipment to detect-many
      cases are undiagnosed or treated under false diagnoses. The author believes that
      undetected temporal lobe epilepsy falsely labelled as psychiatric disorders are
      common. Specific and effective treatment exists for temporal lobe epilepsy,
      making correct diagnosis important. This history-based on the author's personal
      experience-also illustrates aspects of the physician-patients' problems and
      resources, as well as the gap between somatic and psychiatric medicine concerning
      this rather common neuropsychiatric disorder.

PMID- 20671957
TI  - Contribution of Filopodia to Cell Migration: A Mechanical Link between Protrusion
      and Contraction.
AB  - Numerous F-actin containing structures are involved in regulating protrusion of
      membrane at the leading edge of motile cells. We have investigated the structure
      and dynamics of filopodia as they relate to events at the leading edge and the
      function of the trailing actin networks. We have found that although filopodia
      contain parallel bundles of actin, they contain a surprisingly nonuniform spatial
      and temporal distribution of actin binding proteins. Along the length of the
      actin filaments in a single filopodium, the most distal portion contains
      primarily T-plastin, while the proximal portion is primarily bound by alpha
      actinin and coronin. Some filopodia are stationary, but lateral filopodia move
      with respect to the leading edge. They appear to form a mechanical link between
      the actin polymerization network at the front of the cell and the myosin motor
      activity in the cell body. The direction of lateral filopodial movement is
      associated with the direction of cell migration. When lateral filopodia initiate
      from and move toward only one side of a cell, the cell will turn opposite to the
      direction of filopodial flow. Therefore, this filopodia-myosin II system allows
      actin polymerization driven protrusion forces and myosin II mediated contractile
      force to be mechanically coordinated.

PMID- 20671958
TI  - Vaxign: the first web-based vaccine design program for reverse vaccinology and
      applications for vaccine development.
AB  - Vaxign is the first web-based vaccine design system that predicts vaccine targets
      based on genome sequences using the strategy of reverse vaccinology. Predicted
      features in the Vaxign pipeline include protein subcellular location,
      transmembrane helices, adhesin probability, conservation to human and/or mouse
      proteins, sequence exclusion from genome(s) of nonpathogenic strain(s), and
      epitope binding to MHC class I and class II. The precomputed Vaxign database
      contains prediction of vaccine targets for >70 genomes. Vaxign also performs
      dynamic vaccine target prediction based on input sequences. To demonstrate the
      utility of this program, the vaccine candidates against uropathogenic Escherichia
      coli (UPEC) were predicted using Vaxign and compared with various experimental
      studies. Our results indicate that Vaxign is an accurate and efficient vaccine
      design program.

PMID- 20671959
TI  - Molecular Characterization of the Onset and Progression of Colitis in Inoculated
      Interleukin-10 Gene-Deficient Mice: A Role for PPARalpha.
AB  - The interleukin-10 gene-deficient (Il10(-/-)) mouse is a model of human
      inflammatory bowel disease and Ppara has been identified as one of the key genes
      involved in regulation of colitis in the bacterially inoculated Il10(-/-) model.
      The aims were to (1) characterize colitis onset and progression using a
      histopathological, transcriptomic, and proteomic approach and (2) investigate
      links between PPARalpha and IL10 using gene network analysis. Bacterial
      inoculation resulted in severe colitis in Il10(-/-) mice from 10 to 12 weeks of
      age. Innate and adaptive immune responses showed differences in gene expression
      relating to colitis severity. Actin cytoskeleton dynamics, innate immunity, and
      apoptosis-linked gene and protein expression data suggested a delayed remodeling
      process in 12-week-old Il10(-/-) mice. Gene expression changes in 12-week-old
      Il10(-/-) mice were related to PPARalpha signaling likely to control colitis, but
      how PPARalpha activation might regulate intestinal IL10 production remains to be
      determined.

PMID- 20671960
TI  - Nonsteroidal anti-inflammatory drugs for wounds: pain relief or excessive scar
      formation?
AB  - The inflammatory process has direct effects on normal and abnormal wound healing.
      Hypertrophic scar formation is an aberrant form of wound healing and is an
      indication of an exaggerated function of fibroblasts and excess accumulation of
      extracellular matrix during wound healing. Two cytokines--transforming growth
      factor-beta (TGF-beta) and prostaglandin E2 (PGE2)--are lipid mediators of
      inflammation involving wound healing. Overproduction of TGF-beta and suppression
      of PGE2 are found in excessive wound scarring compared with normal wound healing.
      Nonsteroidal anti-inflammatory drugs (NSAIDs) or their selective cyclooxygenase-2
      (COX-2) inhibitors are frequently used as a pain-killer. However, both NSAIDs and
      COX-2 inhibitors inhibit PGE2 production, which might exacerbate excessive scar
      formation, especially when used during the later proliferative phase. Therefore,
      a balance between cytokines and medication in the pathogenesis of wound healing
      is needed. This report is a literature review pertaining to wound healing and is
      focused on TGF-beta and PGE2.

PMID- 20671961
TI  - Occlusion and Temporomandibular Function among Subjects with Mandibular Distal
      Extension Removable Partial Dentures.
AB  - Objective. To quantify effects on occlusion and temporomandibular function of
      mandibular distal extension removable partial dentures in shortened dental
      arches. Methods. Subjects wearing mandibular extension removable partial dentures
      (n = 25) were compared with subjects with shortened dental arches without
      extension (n = 74) and with subjects who had worn a mandibular extension
      removable partial denture in the past (n = 19). Subjects with complete dentitions
      (n = 72) were controls. Data were collected at baseline and at 3-, 6-, and 9-year
      observations. Results. Occlusal activity in terms of reported awareness of
      bruxism and occlusal tooth wear of lower anterior teeth did not differ
      significantly between the groups. In contrast, occlusal tooth wear of premolars
      in shortened dental arches with or without extension dentures was significantly
      higher than in the controls. Differences amongst groups with respect to signs and
      symptoms related to temporomandibular disorders were not found. Occlusal support
      of the dentures did not influence anterior spatial relationship. Occlusal
      contacts of the denture teeth decreased from 70% for second premolars via 50% for
      first molars, to 30% for second molars. Conclusions. Mandibular distal extension
      removable partial dentures in moderate shortened dental arches had no effects on
      occlusion and temporomandibular function.

PMID- 20671962
TI  - Cognitive Sparing during the Administration of Whole Brain Radiotherapy and
      Prophylactic Cranial Irradiation: Current Concepts and Approaches.
AB  - Whole brain radiotherapy (WBRT) for the palliation of metastases, or as
      prophylaxis to prevent intracranial metastases, can be associated with subacute
      and late decline in memory and other cognitive functions. Moreover, these changes
      are often increased in both frequency and severity when cranial irradiation is
      combined with the use of systemic or intrathecal chemotherapy. Approaches to
      preventing or reducing this toxicity include the use of stereotactic radiosurgery
      (SRS) instead of WBRT; dose reduction for PCI; exclusion of the limbic circuit,
      hippocampal formation, and/or neural stem cell regions of the brain during
      radiotherapy; avoidance of intrathecal and/or systemic chemotherapy during
      radiotherapy; the use of high-dose, systemic chemotherapy in lieu of WBRT. This
      review discusses these concepts in detail as well as providing both neuroanatomic
      and radiobiologic background relevant to these issues.

PMID- 20671963
TI  - Serum persistent organic pollutants and duration of lactation among Mexican
      American women.
AB  - BACKGROUND: Research suggests that estrogenic endocrine-disrupting chemicals
      interfere with lactation. OBJECTIVES: (1) to determine if estrogenic persistent
      organic pollutants (POPs) are associated with shortened lactation duration; (2)
      to determine whether previous breastfeeding history biases associations. METHODS
      AND RESULTS: We measured selected organochlorines and polychlorinated biphenyls
      (p, p'-DDE, p, p'-DDT, o, p'-DDT, beta-hexachlorocyclohexane, hexachlorobenzene,
      and PCBs 44, 49, 52, 118, 138, 153, and 180) in serum from 366 low-income,
      Mexican-American pregnant women living in an agricultural region of California
      and assessed breastfeeding duration by questionnaires. We found no association
      between DDE, DDT, or estrogenic POPs with shortened lactation duration, but
      rather associations for two potentially estrogenic POPs with lengthened lactation
      duration arose (HR [95% CI]: 0.6 [0.4, 0.8] for p, p'-DDE & 0.8 [0.6, 1.0] for
      PCB 52). Associations between antiestrogenic POPs (PCBs 138 and 180) and
      shortened lactation duration were attributed to a lactation history bias.
      CONCLUSION: Estrogenic POPs were not associated with shortened lactation
      duration, but may be associated with longer lactation duration.

PMID- 20671964
TI  - ERK5 Contributes to VEGF Alteration in Diabetic Retinopathy.
AB  - Diabetic retinopathy is one of the most common causes of blindness in North
      America. Several signaling mechanisms are activated secondary to hyperglycemia in
      diabetes, leading to activation of vasoactive factors. We investigated a novel
      pathway, namely extracellular signal regulated kinase 5 (ERK5) mediated
      signaling, in modulating glucose-induced vascular endothelial growth factor
      (VEGF) expression. Human microvascular endothelial cells (HMVEC) were exposed to
      glucose. In parallel, retinal tissues from streptozotocin-induced diabetic rats
      were examined after 4 months of follow-up. In HMVECs, glucose caused initial
      activation followed by deactivation of ERK5 and its downstream mediators myocyte
      enhancing factor 2C (MEF2C) and Kruppel-like factor 2 (KLF2) mRNA expression.
      ERK5 inactivation further led to augmented VEGF mRNA expression. Furthermore,
      siRNA mediated ERK5 gene knockdown suppressed MEF2C and KLF2 expression and
      increased VEGF expression and angiogenesis. On the other hand, constitutively
      active MEK5, an activator of ERK5, increased ERK5 activation and ERK5 and KLF2
      mRNA expression and attenuated basal- and glucose-induced VEGF mRNA expression.
      In the retina of diabetic rats, depletion of ERK5, KLF2 and upregulation of VEGF
      mRNA were demonstrated. These results indicated that ERK5 depletion contributes
      to glucose induced increased VEGF production and angiogenesis. Hence, ERK5 may be
      a putative therapeutic target to modulate VEGF expression in diabetic
      retinopathy.

PMID- 20671965
TI  - Mononuclear and Dinuclear Manganese(II) Complexes from the Use of Methyl(2
      pyridyl)ketone Oxime.
AB  - The reactions of methyl(2-pyridyl)ketone oxime, (py)C(Me)NOH, with manganese(II)
      sulfate monohydrate have been investigated. The reaction between equimolar
      quantities of MnSO(4) . H(2)O and (py)C(Me)NOH in H(2)O lead to the dinuclear
      complex [Mn(2)(SO(4))(2){(py)C(Me)NOH}(4)] . (py)C(Me)NOH, 1 . (py)C(Me)NOH,
      while employment of NaOMe as base affords the compound
      [Mn(HCO(2))(2){(py)C(Me)NOH}(2)] (2). The structures of both compounds have been
      determined by single crystal X-ray diffraction. In both complexes, the organic
      ligand chelates through its nitrogen atoms. The IR data are discussed in terms of
      the nature of bonding and the structures of the two complexes.

PMID- 20671966
TI  - Stillbirths in rural hospitals in the gambia: a cross-sectional retrospective
      study.
AB  - Objective. We determined the stillbirth rate and associated factors among women
      who delivered in rural hospitals in The Gambia. Method. A cross-sectional
      retrospective case review of all deliveries between July and December 2008 was
      undertaken. Maternity records were reviewed and abstracted of the mother's
      demographic characteristics, obstetric complications and foetal outcome. MAIN
      OUTCOME MEASURE: The stillbirth rate was calculated as deaths per 1000 births.
      Results. The hospital-based stillbirth rate was high, 156 (95% CI 138-174) per
      1000 births. Of the 1,519 deliveries, there were 237 stillbirths of which 137
      (57.8%) were fresh. Severe obstetric complication, birth weight <2500 g,
      caesarean section delivery, and referral from a peripheral health facility were
      highly significantly associated with higher stillbirth rates, OR = 6.68 (95% CI
      3.84-11.62), 4.47 (95% CI 3.04-6.59), 4.35 (95% CI 2.46-7.69), and 3.82 (95% CI
      2.24-6.51), respectively. Half (50%) of the women with stillbirths had no
      antenatal care OR = 4. 46(95% CI 0.84-23.43). Conclusion. We observed an
      unacceptably high stillbirth rate in this study. As most of the stillbirths were
      fresh, improved intrapartum care supported by emergency transport services and
      skilled personnel could positively impact on perinatal outcomes in rural
      hospitals in The Gambia.

PMID- 20671967
TI  - Parental Influence on Young Children's Physical Activity.
AB  - Parents influence on their young children's physical activity (PA) behaviours was
      examined in a sample of 102 preschool-aged children (54 boys). Questionnaires
      regarding family sociodemographics and physical activity habits were completed.
      Results showed that children who received greater parental support for activity
      (B = .78, P < .10) and had parents who rated PA as highly enjoyable (B = .69, P <
      .05) were significantly more likely to engage in one hour or more of daily PA.
      Being an older child (B = -.08, P < .01), having older parents (B = -.26, P <
      .01), and watching more than one hour of television/videos per day (B = 1.55, P <
      .01) reduced the likelihood that a child would be rated as highly active.
      Children who received greater parental support for PA were 6.3 times more likely
      to be highly active than inactive (B = 1.44, P < .05). Thus, parents can promote
      PA among their preschoolers, not only by limiting TV time but also by being
      highly supportive of their children's active pursuits.

PMID- 20671968
TI  - Finding biomarker signatures in pooled sample designs: a simulation framework for
      methodological comparisons.
AB  - Detection of discriminating patterns in gene expression data can be accomplished
      by using various methods of statistical learning. It has been proposed that
      sample pooling in this context would have negative effects; however, pooling
      cannot always be avoided. We propose a simulation framework to explicitly
      investigate the parameters of patterns, experimental design, noise, and choice of
      method in order to find out which effects on classification performance are to be
      expected. We use a two-group classification task and simulated gene expression
      data with independent differentially expressed genes as well as bivariate linear
      patterns and the combination of both. Our results show a clear increase of
      prediction error with pool size. For pooled training sets powered partial least
      squares discriminant analysis outperforms discriminance analysis, random forests,
      and support vector machines with linear or radial kernel for two of three
      simulated scenarios. The proposed simulation approach can be implemented to
      systematically investigate a number of additional scenarios of practical
      interest.

PMID- 20671969
TI  - Antiretroviral Drug-Associated Oral Lichenoid Reaction in HIV Patient: A Case
      Report.
AB  - Antiretroviral therapy has changed the course of HIV disease and improved quality
      of life in HIV patients. Incidence of an oral lichenoid drug reaction induced by
      zidovudine is not common. Once it occurs, it affects a patient's well being, in
      particular their oral functions. Here we report the first case of a 34-year-old
      Thai man with painful erosive lesions involving the lip and buccal mucosa.
      Treatment with topical fluocinolone acetonide 0.1% alleviated the patient's oral
      pain, but it was not until the subsequent withdrawal of zidovudine that the
      patient showed improvement and resolution of the lesions. Long-term follow-up was
      useful in the management of this patient, and no recurrence of the lesion was
      found during 21-month follow-up in this patient.

PMID- 20671970
TI  - Electrochemical performances of electroactive nano-layered organic-inorganic
      perovskite containing trivalent iron ion and its use for a DNA biosensor
      preparation.
AB  - A steady nano organic-inorganic perovskite hybrid with [H(2)3-AMP](3/2)Fe(CN)(6)
      (3-AMP = 3-methylaminopyridine) was prepared in the air. The structure is an
      unusual layered organic-inorganic type. The resulting hybrid enveloped in
      paraffin to prepare [H(2)3-AMP](3/2)Fe(CN)(6) paste electrode (HPE) shows good
      electrochemical activity and a couple of oxidation and reduction peaks with
      potential of cyclic voltammometry (CV) at around 440 mV and 30 mV. Compared with
      that on CPE, oxidation potential of Fe(CN)(6) (3-) on HPE shifts negatively 259.7
      mV and that of reduction shifts positively 338.7 mV, which exhibits that [H(2)3
      AMP](3/2)Fe(CN)(6) can accelerate the electron-transfer to improve the
      electrochemical reaction reversibility. Such characteristics of [H(2)3
      AMP](3/2)Fe(CN)(6) have been employed to prepare the DNA biosensor. The single
      strand DNA (ssDNA) and double-strand DNA (dsDNA) immobilized on HPE,
      respectively, can improve the square wave voltammometry (SWV) current and SWV
      potential shifts positively. The effect of pH was evaluated. And there is
      hybridization peak on SWV curve using HPE immobilized ssDNA in the complementary
      ssDNA solution. And HPE immobilized ssDNA can be utilized to monitor the DNA
      hybridization and detect complementary ssDNA, covering range from 3.24 x 10(-7)
      to 6.72 x 10(-5) g/mL with detection limit of 1.57 x 10(-7) g/mL. The DNA
      biosensor exhibits a good stability and reproducibility.

PMID- 20671971
TI  - Identification of phylogenetic position in the Chlamydiaceae family for Chlamydia
      strains released from monkeys and humans with chlamydial pathology.
AB  - Based on the results of the comparative analysis concerning relatedness and
      evolutional difference of the 16S-23S nucleotide sequences of the middle
      ribosomal cluster and 23S rRNA I domain, and based on identification of
      phylogenetic position for Chlamydophila pneumoniae and Chlamydia trichomatis
      strains released from monkeys, relatedness of the above stated isolates with
      similar strains released from humans and with strains having nucleotide sequences
      presented in the GenBank electronic database has been detected for the first time
      ever. Position of these isolates in the Chlamydiaceae family phylogenetic tree
      has been identified. The evolutional position of the investigated original
      Chlamydia and Chlamydophila strains close to analogous strains from the Gen-Bank
      electronic database has been demonstrated. Differences in the 16S-23S nucleotide
      sequence of the middle ribosomal cluster and 23S rRNA I domain of plasmid and
      nonplasmid Chlamydia trachomatis strains released from humans and monkeys
      relative to different genotype groups (group B-B, Ba, D, Da, E, L1, L2, L2a;
      intermediate group-F, G, Ga) have been revealed for the first time ever.
      Abnormality in incA chromosomal gene expression resulting in Chlamydia life
      development cycle disorder, and decrease of Chlamydia virulence can be related to
      probable changes in the nucleotide sequence of the gene under consideration.

PMID- 20671972
TI  - The effect of stereochemistry on sodium ion complexation in nucleoside
      metallacarborane conjugates.
AB  - CONJUGATES OF PURINE AND PYRIMIDINE NUCLEOSIDES: thymidine and 2'-deoxyguanosine
      with cobalt-metallacarborane were studied for their sodium ion complexing
      properties. Formation of stable complexes of 1 : 1 stoichiometry was proved by
      ESI MS spectroscopy and (23)Na NMR. Equilibrium constants and energies of complex
      formation were calculated. Complexation of alkali-metals by nucleoside
      metallacarborane conjugates may affect the physicochemical and biological
      properties of the conjugates and should be taken into consideration during
      biological evaluation of these types of modifications.

PMID- 20671974
TI  - Multimodal therapy for the treatment of severe ischemic stroke combining
      endovascular embolectomy and stenting of long intracranial artery occlusion.
AB  - Embolic occlusion of cerebral arteries is a major cause for stroke. Intravenous
      thrombolysis showed positive results in this condition, however even when strict
      criteria are used, the risk of hemorrhagic transformation is possible.
      Microsurgical embolectomy has been described earlier. Purpose. We performed
      multimodal therapy of cerebral artery occlusion. Case Report. We present a case
      of a 49-year-old female patient who-according to the National Institute of Health
      Stroke Scale (NIHSS)-was rated as 19 due to acute occlusion of the horizontal
      segment of the left middle cerebral artery (MCA). After failed i.v. thrombolysis,
      only a part of the clot could be evacuated by the endovascular approach-without
      restoration of blood flow. Normal patency of the left MCA was re-established
      after stenting. Within 72 hours, the patient had an NIHSS score of 14, with a
      small haematoma in the left hemisphere. Conclusion. In our case multimodal
      therapy combining i.v. thrombolysis, mechanical disruption of thrombus, MCA
      stenting and platelet function antagonists, resulted in successful recanalization
      of the acutely occluded left MCA.

PMID- 20671973
TI  - Desmosomal molecules in and out of adhering junctions: normal and diseased States
      of epidermal, cardiac and mesenchymally derived cells.
AB  - Current cell biology textbooks mention only two kinds of cell-to-cell adhering
      junctions coated with the cytoplasmic plaques: the desmosomes (maculae
      adhaerentes), anchoring intermediate-sized filaments (IFs), and the actin
      microfilament-anchoring adherens junctions (AJs), including both punctate (puncta
      adhaerentia) and elongate (fasciae adhaerentes) structures. In addition, however,
      a series of other junction types has been identified and characterized which
      contain desmosomal molecules but do not fit the definition of desmosomes. Of
      these special cell-cell junctions containing desmosomal glycoproteins or proteins
      we review the composite junctions (areae compositae) connecting the
      cardiomyocytes of mature mammalian hearts and their importance in relation to
      human arrhythmogenic cardiomyopathies. We also emphasize the various plakophilin
      2-positive plaques in AJs (coniunctiones adhaerentes) connecting proliferatively
      active mesenchymally-derived cells, including interstitial cells of the heart and
      several soft tissue tumor cell types. Moreover, desmoplakin has also been
      recognized as a constituent of the plaques of the complexus adhaerentes
      connecting certain lymphatic endothelial cells. Finally, we emphasize the
      occurrence of the desmosomal transmembrane glycoprotein, desmoglein Dsg2, out of
      the context of any junction as dispersed cell surface molecules in certain types
      of melanoma cells and melanocytes. This broadening of our knowledge on the
      diversity of AJ structures indicates that it may still be too premature to close
      the textbook chapters on cell-cell junctions.

PMID- 20671975
TI  - Targeted immunotherapy with rituximab leads to a transient alteration of the IgG
      autoantibody profile in pemphigus vulgaris.
AB  - In pemphigus vulgaris (PV), IgG autoantibodies against the ectodomain of
      desmoglein 3 (Dsg3) have been shown to be directly responsible for the loss of
      keratinocyteadhesion. The aim of the present study was to study the effect of the
      B cell depleting anti-CD20 monoclonal antibody, rituximab, on the profile of
      pathogenic IgG against distinct regions of the Dsg3 ectodomain in 22 PV patients
      who were followed up clinically and serologically by Dsg3 ELISA over 12-24
      months. Prior to rituximab, all the 22 PV patients showed IgG against Dsg3
      (Dsc3EC1-5). Specifically, 14/22 showed IgG reactivity against the Dsg3EC1
      subdomain, 5/22 patients against Dsg3EC2, 7/22 against Dsg3EC3, 11/22 against
      Dsg3EC4, and 2/22 against Dsg3EC5. Within 6 months after rituximab, all the
      patients showed significant clinical improvement and reduced IgG against Dsg3
      (5/22) and the various subdomains, that is, Dsg3EC1 (7/22), Dsg3EC2 (3/22),
      Dsg3EC3 (2/22), sg3EC4 (2/22), and Dsg3EC5 (0/22). During the entire observation
      period, 6/22 PV patients experienced a clinical relapse which was associated with
      the reappearance of IgG against previously recognized Dsg3 subdomains,
      particularly against the Dsg3EC1. Thus, in PV, rituximab only temporarily
      depletes pathogenic B cell responses against distinct subdomains of Dsg3 which
      reappear upon clinical relapse.

PMID- 20671976
TI  - A Comprehensive Study of Progressive Cytogenetic Alterations in Clear Cell Renal
      Cell Carcinoma and a New Model for ccRCC Tumorigenesis and Progression.
AB  - We present a comprehensive study of cytogenetic alterations that occur during the
      progression of clear cell renal cell carcinoma (ccRCC). We used high-density high
      throughput Affymetrix 100 K SNP arrays to obtain the whole genome SNP copy number
      information from 71 pretreatment tissue samples with RCC tumors; of those, 42
      samples were of human ccRCC subtype. We analyzed patterns of cytogenetic loss and
      gain from different RCC subtypes and in particular, different stages and grades
      of ccRCC tumors, using a novel algorithm that we have designed. Based on patterns
      of cytogenetic alterations in chromosomal regions with frequent losses and gains,
      we inferred the involvement of candidate genes from these regions in ccRCC
      tumorigenesis and development. We then proposed a new model of ccRCC
      tumorigenesis and progression. Our study serves as a comprehensive overview of
      cytogenetic alterations in a collection of 572 ccRCC tumors from diversified
      studies and should facilitate the search for specific genes associated with the
      disease.

PMID- 20671977
TI  - Chronic diarrhea and pancolitis caused by paracoccidioidomycosis: a case report.
AB  - South American blastomycosis is a systemic micosis caused by infection with
      Paracoccidioides brasiliensis. The most frequently affected sites are the lower
      lip buccal mucous membrane, palate, tongue, sublingual region, lymph glands, and
      lungs. However, colonic involvement is not a common expression of
      Paracoccidioidomycosis. We report a case of chronic diarrhea and pancolitis
      caused by Paracoccidioidomycosis with fatal outcome.

PMID- 20671978
TI  - Antineoplastic Activity of New Transition Metal Complexes of 6-Methylpyridine-2
      carbaldehyde-N(4)-ethylthiosemicarbazone: X-Ray Crystal Structures of
      [VO(2)(mpETSC)] and [Pt(mpETSC)Cl].
AB  - New complexes of dioxovanadium(V), zinc(II), ruthenium(II), palladium(II), and
      platinum(II) with 6-methylpyridine-2-carbaldehyde-N(4)-ethylthiosemicarbazone
      (HmpETSC) have been synthesized. The composition of these complexes is discussed
      on the basis of elemental analyses, IR, Raman, NMR ((1)H, (13)C, and (31)P), and
      electronic spectral data. The X-ray crystal structures of [VO(2)(mpETSC)] and
      [Pt(mpETSC)Cl] are also reported. The HmpETSC and its [Zn(HmpETSC)Cl(2)] and
      [Pd(mpETSC)Cl] complexes exhibit antineoplastic activity against colon cancer
      human cell lines (HCT 116).

PMID- 20671980
TI  - Valproate in conversion disorder: a case report.
AB  - Few data are in literature about the pharmacological treatment of conversion
      disorder and there are not any studies about the use of Valproate extended
      release (ER) in treating conversion disorder. In this article, we are reporting a
      case of an Italian woman with a diagnosis of conversion disorder treated
      effectively and quickly by Valproate ER.

PMID- 20671979
TI  - PROCARB: A Database of Known and Modelled Carbohydrate-Binding Protein Structures
      with Sequence-Based Prediction Tools.
AB  - Understanding of the three-dimensional structures of proteins that interact with
      carbohydrates covalently (glycoproteins) as well as noncovalently (protein
      carbohydrate complexes) is essential to many biological processes and plays a
      significant role in normal and disease-associated functions. It is important to
      have a central repository of knowledge available about these protein-carbohydrate
      complexes as well as preprocessed data of predicted structures. This can be
      significantly enhanced by tools de novo which can predict carbohydrate-binding
      sites for proteins in the absence of structure of experimentally known binding
      site. PROCARB is an open-access database comprising three independently working
      components, namely, (i) Core PROCARB module, consisting of three-dimensional
      structures of protein-carbohydrate complexes taken from Protein Data Bank (PDB),
      (ii) Homology Models module, consisting of manually developed three-dimensional
      models of N-linked and O-linked glycoproteins of unknown three-dimensional
      structure, and (iii) CBS-Pred prediction module, consisting of web servers to
      predict carbohydrate-binding sites using single sequence or server-generated
      PSSM. Several precomputed structural and functional properties of complexes are
      also included in the database for quick analysis. In particular, information
      about function, secondary structure, solvent accessibility, hydrogen bonds and
      literature reference, and so forth, is included. In addition, each protein in the
      database is mapped to Uniprot, Pfam, PDB, and so forth.

PMID- 20671981
TI  - Acute Cardiac Failure due to Intra-Atrial Mass Caused by Zygomycetes in an
      Immunocompromised Paediatric Patient.
AB  - Cardiac zygomycosis can be a critical condition with sudden onset of severe
      congestive heart failure followed by severe hemodynamic deterioration. We report
      a fatal course of disseminated fungal infection with a massive intra-atrial
      thrombosis caused by a zygomycete, in a five year old boy treated for acute
      lymphoblastic leukaemia. In addition, we discuss the literature concerning
      infections caused by zygomycetes involving the heart. Prognosis is poor. A high
      index of suspicion and an aggressive diagnostic and therapeutic approach with the
      prompt start of preemptive antifungal therapy are key factors to improve outcome.

PMID- 20671982
TI  - Deoxycorticosterone producing tumor as a cause of resistant hypertension.
AB  - We describe a young woman with longstanding resistant hypertension. Evaluation
      for renal artery stenosis and primary aldosteronism was unrevealing. In this
      setting of a suppressed plasma aldosterone concentration (PAC) and a suppressed
      plasma renin activity (PRA), a differential diagnosis of a deoxycorticosterone
      (DOC) producing tumor was entertained. Biochemical and imaging studies confirmed
      this diagnosis. Rare and novel DOC producing tumors are an important cause of
      resistant hypertension.

PMID- 20671984
TI  - Primary malignant fibrous histiocytoma of the lung: a case report.
AB  - Primary malignant fibrous histiocytoma (MFH) of the lung is extremely rare
      although it is among the most common soft tissue sarcomas in adults. Surgery is
      the primary mode of therapy, with high rates of local and distant recurrence,
      while radiation therapy appears to be a very useful adjunct, decreasing local
      relapse. We report a case of primary malignant fibrous histiocytoma of the lung.
      Fourteen years after surgical resection, the patient is still alive although with
      multiple metastatic lesions throughout his body.

PMID- 20671983
TI  - Task effects on BOLD signal correlates of implicit syntactic processing.
AB  - BOLD signal was measured in sixteen participants who made timed font change
      detection judgments in visually presented sentences that varied in syntactic
      structure and the order of animate and inanimate nouns. Behavioral data indicated
      that sentences were processed to the level of syntactic structure. BOLD signal
      increased in visual association areas bilaterally and left supramarginal gyrus in
      the contrast of sentences with object- and subject-extracted relative clauses
      without font changes in which the animacy order of the nouns biased against the
      syntactically determined meaning of the sentence. This result differs from the
      findings in a non-word detection task (Caplan et al, 2008a), in which the same
      contrast led to increased BOLD signal in the left inferior frontal gyrus. The
      difference in areas of activation indicates that the sentences were processed
      differently in the two tasks. These differences were further explored in an eye
      tracking study using the materials in the two tasks. Issues pertaining to how
      parsing and interpretive operations are affected by a task that is being
      performed, and how this might affect BOLD signal correlates of syntactic
      contrasts, are discussed.

PMID- 20671985
TI  - Halo, Alkyl, Aryl, and Bis(imido) Complexes of Niobium Supported by the beta
      Diketiminato Ligand.
AB  - Synthesis of the complex (BDI)Nb(N(t)Bu)Cl(2)py (BDI = HC[C(Me)N(2,6-iPr(2)
      C(6)H(3))](2)) was achieved in high yield following the treatment of
      Nb(N(t)Bu)Cl(3)py(2) with Li(BDI)(OEt(2)). Substitution of the chlorides for
      fluorides was effected by introducing 2.0 equiv of Me(3)SnF in toluene, providing
      the pyridine-coordinated difluoride complex (BDI)Nb(N(t)Bu)F(2)py in modest
      yield. The pyridine ligands from both halide compounds were removed by treatment
      of the pyridine adducts with B(C(6)F(5))(3), affording the Lewis base-free
      complexes (BDI)Nb(NtBu)X(2) (X = Cl, F). Additionally, the Lewis base-free
      dichlorides of the (t)Bu-imido and Ar-imido (Ar = 2,6-(i)Pr(2)-C(6)H(3))
      complexes were obtained following treatment of Nb(NR)Cl(3)(dme) (R = tBu, Ar)
      with Li(BDI)(OEt(2)). The pyridine-coordinated dichloride was alkylated and
      arylated to form the dimethyl complex (BDI)Nb(N(t)Bu)Me(2) (described previously,
      see text) and the mono(p-tolyl) complex (BDI)Nb(N(t)Bu)Cl(p-tol), the latter of
      which was methylated with MeMgBr to yield the mixed alkyl/aryl complex
      (BDI)Nb(N(t)Bu)Me(p-tol) in good yield. A rare example of a Group 5 bis((t)Bu
      imido) species was synthesized in good yield via treatment of
      (BDI)Nb(N(t)Bu)Cl(2)py with 2.0 equiv of LiNHtBu to form (BDI)Nb(NtBu)(2)py.
      Exchange of the coordinated pyridine ligand for either pyridine-d(5) or dmap (p
      (dimethylamino)pyridine) was shown to occur through a dissociative mechanism,
      allowing for removal of the coordinated Lewis base by treatment with
      B(C(6)F(5))(3). The resulting average C(2v)-symmetric tetracoordinate bis(imido)
      complex (BDI)Nb(N(t)Bu)(2) was characterized in solution by NMR spectroscopy and
      observed to undergo clean thermal decomposition to yield
      (BDI(#))Nb(N(t)Bu)(NH(t)Bu) (BDI(#) = H(2)C=C(NAr)CH=C(NAr)Me) over several hours
      at room temperature. Treatment of the four-coordinate bis(imido) with (t)BuNCO
      resulted in clean [2 + 2] cycloaddition to yield an oxaazametallacyclobutane
      complex, which was further observed to extrude (t)BuN=C=N(t)Bu over 12 h at room
      temperature. The molecular structures of (BDI)Nb(N(t)Bu)Cl(2)py,
      (BDI)Nb(NAr)Cl(2), (BDI)Nb(N(t)Bu)Me(2), (BDI)Nb(N(t)Bu)Cl(p-tol),
      (BDI)Nb(N(t)Bu)(2)py, and (BDI)Nb(NtBu)(2)(dmap) were determined
      crystallographically. Finally, DFT (BP86) geometry optimization calculations on a
      model complex of the thermally unstable four-coordinate bis(imido) species
      allowed for identification of the orbital interactions leading to activation of
      the imido groups through mixing with the BDI frontier orbitals.

PMID- 20671986
TI  - Evaluating Convergence of Within-Person Change and Between-Person Age Differences
      in Age-Heterogeneous Longitudinal Studies.
AB  - The distinction of between-person age differences from within-person age changes
      is necessary for understanding aging-related change processes. Although
      longitudinal studies are required to address issues relating to within person
      change, most studies begin using age-heterogeneous samples and conclude using
      survival-heterogeneous samples. Given the numerous potential confounds associated
      with age-heterogeneous samples, careful treatment of between-person age
      differences is essential to obtain the correct inferences regarding within-person
      age change. We demonstrate how failure to differentiate between-person age
      effects (and by extension, of survival age or other effects producing sample
      heterogeneity) will lead to uninterpretable inferences regarding within-person
      change. We recommend that convergence of age differences and age changes be
      formally evaluated whenever possible.

PMID- 20671987
TI  - Remote postoperative epidural hematoma after subdural hygroma drainage.
AB  - Objective. Subdural hygroma is reported to occur in 5%-20% of all patients with
      closed head trauma, the treatment is controversial and in symptomatic cases
      surgical drainage is need. We report on a new case with remote acute epidural
      hematoma (AEH) after subdural hygroma drainage. Case Presentation. A 38-year-old
      man suffered blunt head trauma and had diffuse axonal injury grade III in CT
      scan. A CT scan that was late performed showed an increasing subdural fluid
      collection with mild mass effect and some effacement of the left lateral
      ventricle. We perform a trepanation with drainage of a hypertensive subdural
      collection with citrine aspect. Postoperative tomography demonstrated a large
      left AEH. Craniotomy and evacuation of the hematoma were performed. Conclusion.
      The mechanism of remote postoperative AEH formation is unclear. Complete reliance
      on neurologic monitoring, trust in an early CT scan, and a relative complacency
      after an apparently successful initial surgery for hygroma drainage may delay the
      diagnosis of this postoperative AEH.

PMID- 20671989
TI  - Adverse Interaction between Capecitabine and Warfarin Resulting in Altered
      Coagulation Parameters: A Review of the Literature Starting from a Case Report.
AB  - Capecitabine is an orally active prodrug of fluorouracil and is extensively used
      as an antineoplastic agent. It is converted to 5-Fluorouracil in the liver and
      tumor tissues. Warfarin is an anticoagulant agent for preventing and treating
      venous and arterial thrombosis and embolism and is metabolized by cytochrome P450
      isoenzymes in the liver. Preclinical in vitro studies using human liver
      microsomes report no inhibitory effects between capecitabine and substrates of
      cytochrome P. However, the concomitant administration of capecitabine and
      warfarin resulted in INR elevation in the cases previously reported in the
      literature. The exact mechanism of this interaction is unknown but may be related
      to downregulation of cytochrome P450 2C9 by capecitabine or its metabolites. We
      report on the possible adverse interaction between capecitabine and warfarin in a
      patient with metastatic breast cancer and critically review the existing
      literature on this topic. Physicians should be aware of adverse reactions arising
      from the combined use of capecitabine and warfarin. In the light of the current
      data, INR levels should be closely monitored in patients using these drugs
      together.

PMID- 20671990
TI  - Sieve Maximum Likelihood Estimation for Doubly Semiparametric Zero-Inflated
      Poisson Models.
AB  - For nonnegative measurements such as income or sick days, zero counts often have
      special status. Furthermore, the incidence of zero counts is often greater than
      expected for the Poisson model. This article considers a doubly semiparametric
      zero-inflated Poisson model to fit data of this type, which assumes two partially
      linear link functions in both the mean of the Poisson component and the
      probability of zero. We study a sieve maximum likelihood estimator for both the
      regression parameters and the nonparametric functions. We show, under routine
      conditions, that the estimators are strongly consistent. Moreover, the parameter
      estimators are asymptotically normal and first-order efficient, while the
      nonparametric components achieve the optimal convergence rates. Simulation
      studies suggest that the extra flexibility inherent from the doubly
      semiparametric model is gained with little loss in statistical efficiency. We
      also illustrate our approach with a dataset from a public health study.

PMID- 20671991
TI  - An Empirical Analysis of the Current Need for Teleneuromedical Care in German
      Hospitals without Neurology Departments.
AB  - Indroduction. At present, modern telemedicine methods are being introduced, that
      may contribute to reducing lack of qualified stroke patient care, particularly in
      less populated regions. With the help of video conferencing systems, a so-called
      neuromedical teleconsultation is carried out. Methods. The study included a
      multicentered, completely standardized survey of physicians in hospitals by means
      of a computerized on-line questionnaire. Descriptive statistical methods were
      used for data analysis. Results. 119 acute hospitals without neurology
      departments were included in the study. The most important reasons for
      participating in a teleneuromedical network is seen as the improvement in the
      quality of treatment (82%), the ability to avoid unnecessary patient transport
      (76%), easier and faster access to stroke expertise (72%) as well as better
      competitiveness among medical services (67%). The most significant problem areas
      are the financing system of teleneuromedicine with regard to the acquisition
      costs of the technical equipment (43%) and the compensation for the stroke-unit
      center with the specialists' consultation service (31%) as well as legal aspects
      of teleneuromedicine (27%). Conclusions. This investigation showed that there is
      a high acceptance for teleneuromedicine among co-operating hospitals. However
      these facilities have goals in addition to improved quality in stroke treatment.
      Therefore the use of teleneuromedicine must be also associated with long term
      incentives for the overall health care system, particularly since the
      implementation of a teleneuromedicine network system is time consuming and
      associated with high implementation costs.

PMID- 20671988
TI  - Joint aging and chondrocyte cell death.
AB  - Articular cartilage extracellular matrix and cell function change with age and
      are considered to be the most important factors in the development and
      progression of osteoarthritis. The multifaceted nature of joint disease indicates
      that the contribution of cell death can be an important factor at early and late
      stages of osteoarthritis. Therefore, the pharmacologic inhibition of cell death
      is likely to be clinically valuable at any stage of the disease. In this article,
      we will discuss the close association between diverse changes in cartilage aging,
      how altered conditions influence chondrocyte death, and the implications of
      preventing cell loss to retard osteoarthritis progression and preserve tissue
      homeostasis.

PMID- 20671992
TI  - Review of prediction models to estimate activity-related energy expenditure in
      children and adolescents.
AB  - Purpose. To critically review the validity of accelerometry-based prediction
      models to estimate activity energy expenditure (AEE) in children and adolescents.
      Methods. The CINAHL, EMBASE, PsycINFO, and PubMed/MEDLINE databases were
      searched. Inclusion criteria were development or validation of an accelerometer
      based prediction model for the estimation of AEE in healthy children or
      adolescents (6-18 years), criterion measure: indirect calorimetry, or doubly
      labelled water, and language: Dutch, English or German. Results. Nine studies
      were included. Median methodological quality was 5.5 +/- 2.0 IR (out of a maximum
      10 points). Prediction models combining heart rate and counts explained 86-91% of
      the variance in measured AEE. A prediction model based on a triaxial
      accelerometer explained 90%. Models derived during free-living explained up to
      45%. Conclusions. Accelerometry-based prediction models may provide an accurate
      estimate of AEE in children on a group level. Best results are retrieved when the
      model combines accelerometer counts with heart rate or when a triaxial
      accelerometer is used. Future development of AEE prediction models applicable to
      free-living scenarios is needed.

PMID- 20671993
TI  - Nonclassic congenital adrenal hyperplasia.
AB  - Nonclassic congenital adrenal hyperplasia (NCAH) due to P450c21 (21-hydroxylase
      deficiency) is a common autosomal recessive disorder. This disorder is due to
      mutations in the CYP21A2 gene which is located at chromosome 6p21. The clinical
      features predominantly reflect androgen excess rather than adrenal insufficiency
      leading to an ascertainment bias favoring diagnosis in females. Treatment goals
      include normal linear growth velocity and "on-time" puberty in affected children.
      For adolescent and adult women, treatment goals include regularization of menses,
      prevention of progression of hirsutism, and fertility. This paper will review key
      aspects regarding pathophysiology, diagnosis, and treatment of NCAH.

PMID- 20671995
TI  - Adenoidectomy: our approach.

PMID- 20671994
TI  - The tsim tsoum approaches for prevention of cardiovascular disease.
AB  - The Tsim Tsoum Concept means that humans evolved on a diet in which nature
      recommends to ingest fatty acids in a balanced ratio (polyunsaturated(P) :
      saturated(S) =w-6 : w-3 = 1 : 1)as part of dietary lipid pattern where
      monounsaturated fatty acids(MUFA) is the major fatty acid(P : M : S = 1 : 6 : 1)
      in the background of other dietary factors; antioxidants, vitamins, minerals and
      fiber as well as physical activity and low mental stress. Several hundred years
      ago, our diet included natural foods; fruits, vegetables, green vegetables,
      seeds, eggs and honey. Fish, and wild meat were also available to pre
      agricultural humans which shaped modern human genetic nutritional requirement.
      Cereal grains (refined), and vegetable oils that are rich in w-6 fatty acids are
      relatively recent addition to the human diet that represent dramatic departure
      from those foods to which we are adapted. Excess of linoleic acid, trans fatty
      acids (TFA), saturated and total fat as well as refined starches and sugar are
      proinflammatory. Low dietary MUFA and n-3 fatty acids and other long chain
      polyunsarurated fatty acids (LCPUFA) are important in the pathogenesis of
      metabolic syndrome. Increased sympathetic activity with greater secretion of
      neurotransmitters in conjunction of underlying long chain PUFA deficiency, and
      excess of proinflammatory nutrients, may damage the neurons via proinflammatory
      cytokines, in the ventromedial hypothalamus and insulin receptors in the
      brain.Since, 30-50% of the fatty acids in the brain are LCPUFA, especially omega
      3 fatty acids, which are incorporated in the cell membrane phospholipids, it is
      possible that their supplementation may be protective.Blood lipid composition
      does reflect one's health status: (a) circulating serum lipoproteins and their
      ratio provide information on their atherogenicity to blood vessels and (b)
      circulating plasma fatty acids, such as w-6/w-3 fatty acid ratio, give indication
      on proinflammatory status of blood vessels, cardiomyocytes, liver cells and
      neurones; (a) and (b) are phenotype-related and depend on genetic, environmental
      and developmental factors. As such, they appear as universal markers for holistic
      health and these may be important in the pathogenesis of cardiovascular diseases
      and cancer, which is the main consideration of Tsim Tsoum concept.

PMID- 20671996
TI  - Sensitive spectrophotometric method for quantitation of guaifenesin and
      dropropizine in their dosage forms.
AB  - Guaifenesin and dropropizine were analyzed through oxidation with periodic acid
      to give formaldehyde which was allowed to condense with 4-Amino-5-hydrazino-4H
      [1,2,4]-triazole-3-thiol (AHTT). The condensation product was further oxidized to
      yield a purple colored compound with maximum absorption at 550 nm. Beer's law was
      obeyed in the range of 5-45 mug mL(-1) for guaifenesin and 10-80 mug mL(-1) for
      dropropizine. Both drugs were also successfully determined in their dosage forms.

PMID- 20671997
TI  - Desmosomes in vivo.
AB  - The structure, function, and regulation of desmosomal adhesion in vivo are
      discussed. Most desmosomes in tissues exhibit calcium-independent adhesion, which
      is strongly adhesive or "hyperadhesive". This is fundamental to tissue strength.
      Almost all studies in culture are done on weakly adhesive, calcium-dependent
      desmosomes, although hyperadhesion can be readily obtained in confluent cell
      culture. Calcium dependence is a default condition in vivo, found in wounds and
      embryonic development. Hyperadhesion appears to be associated with an ordered
      arrangement of the extracellular domains of the desmosomal cadherins, which gives
      rise to the intercellular midline identified in ultrastructural studies. This in
      turn probably depends on molecular order in the desmosomal plaque. Protein kinase
      C downregulates hyperadhesion and there is preliminary evidence that it may also
      be regulated by tyrosine kinases. Downregulation of desmosomes in vivo may occur
      by internalisation of whole desmosomes rather than disassembly. Hyperadhesion has
      implications for diseases such as pemphigus.

PMID- 20671998
TI  - Severe ventral erosion of penis caused by indwelling urethral catheter and
      inflation of Foley balloon in urethra-need to create list of "never events in
      spinal cord injury" in order to prevent these complications from happening in
      paraplegic and tetraplegic patients.
AB  - Never Events are serious, largely preventable patient safety incidents that
      should not occur if the available preventative measures have been implemented. We
      propose that a list of "Never Events" is created for spinal cord injury patients
      in order to improve the quality of care. To begin with, following two preventable
      complications related to management of neuropathic bladder may be included in
      this list of "Never Events." (i) Severe ventral erosion of glans penis and penile
      shaft caused by indwelling urethral catheter; (ii) incorrect placement of a Foley
      catheter leading to inflation of Foley balloon in urethra. If a Never Event
      occurs, health professionals should report the incident through hospital risk
      management system to National Patient Safety Agency's Reporting and Learning
      System, communicate with the patient, family, and their carer as soon as possible
      about the incident, undertake a comprehensive root cause analysis of what went
      wrong, how, and why, and implement the changes that have been identified and
      agreed following the root cause analysis.

PMID- 20671999
TI  - State-of-the-Art Management of Complications of Myeloma and Its Treatment.
AB  - Multiple myeloma is an incurable disease, although patient survival has increased
      with the availability of novel agents. Both multiple myeloma and its therapies
      often affect the renal, immune, skeletal, hematologic, and nervous systems. The
      resulting organ dysfunctions often impair the quality of life of affected
      patients, complicate and limit subsequent therapies, and may result in
      significant mortality. Research on the treatment of complications of multiple
      myeloma has been limited; hence, preventative and management strategies for
      patients with these complications are heterogeneous and often based on anecdotal
      experience. In this paper, we review the effects of myeloma and the novel
      therapies on organ systems and suggest management strategies.

PMID- 20672000
TI  - Indeterminate cell histiocytosis in association with acute myeloid leukemia.
AB  - Indeterminate cell histiocytosis (ICH) is a rare proliferative disorder, in which
      the predominant cells share morphologic and immunophenotypic features from both
      Langerhans and non-Langerhans cell histiocytosis. We describe a 62-year-old man
      presenting a 2-month history of firm nodular lesions on the upper lip.
      Histopathology, immunohistochemical, and ultrastructural analysis showed typical
      findings of ICH. The patient was treated with thalidomide and almost complete
      regression of the lesions was reached within 7 months. Nevertheless, one month
      after remission, he developed an acute myeloid leukemia of the subtype monocytic
      leukemia (M5). The patient's condition rapidly worsened and he died due to a
      respiratory failure four weeks later. We present this case because apart of being
      rare it joins the effectiveness of thalidomide and the association with an acute
      monocytic leukemia. A review of the literature is made.

PMID- 20672001
TI  - Metastatic melanomas express inhibitory low affinity fc gamma receptor and escape
      humoral immunity.
AB  - Our research, inspired by the pioneering works of Isaac Witz in the 1980s,
      established that 40% of human metastatic melanomas express ectopically inhibitory
      Fc gamma receptors (FcgammaRIIB), while they are detected on less than 5% of
      primary cutaneous melanoma and not on melanocytes. We demonstrated that these
      tumoral FcgammaRIIB act as decoy receptors that bind the Fc portion of
      antimelanoma IgG, which may prevent Fc recognition by the effector cells of the
      immune system and allow the metastatic melanoma to escape the humoral/natural
      immune response. The FcgammaRIIB is able to inhibit the ADCC (antibody dependent
      cell cytotoxicity) in vitro. Interestingly, the percentage of melanoma expressing
      the FcgammaRIIB is high (70%) in organs like the liver, which is rich in
      patrolling NK (natural killer) cells that exercise their antitumoral activity by
      ADCC. We found that this tumoral FcgammaRIIB is fully functional and that its
      inhibitory potential can be triggered depending on the specificity of the anti
      tumor antibody with which it interacts. Together these observations elucidate how
      metastatic melanomas interact with and potentially evade humoral immunity and
      provide direction for the improvement of anti-melanoma monoclonal antibody
      therapy.

PMID- 20672002
TI  - CRT in Patients with Heart Failure: Time Course of Perfusion and Wall Motion
      Changes.
AB  - In patients treated with CRT no data relative to the relationship between
      regional wall motion and perfusion and reverse remodelling of the left ventricle
      at short and medium term followup were available. To this aim, 36 heart failure
      patients were studied by G-SPECT before (T0), within 2 months (T1) and 6 months
      (T2) after CRT. A clinical followup was completed for 36 months. In 30/36
      patients there was an improvement of NYHA Class at T1 that persisted at T2. G
      SPECT showed significant improvement of perfusion at T1 in 92% of patients
      without further changes at T2. A reduction of LV volumes, an increase of EF and
      an improvement of regional wall motion and thickening were observed at T1 versus
      baseline, with only minor changes at T2. Moreover, baseline extension of
      perfusion defects was scarcely correlated with improvement after CRT. Finally,
      end diastolic volume, perfusion defect and diabetes mellitus were independent
      predictors of survival. The main effects of CRT on regional myocardial perfusion
      and wall motion are obtained within 2 months. Volume overload modulates recovery
      of ventricular function independently of reperfusion and, with extension of
      perfusion abnormalities and diabetes were independent predictors of survival
      during followup.

PMID- 20672004
TI  - The sensitivity and specificity of potassium hydroxide smear and fungal culture
      relative to clinical assessment in the evaluation of tinea pedis: a pooled
      analysis.
AB  - Background. There are relatively few studies published examining the sensitivity
      and specificity of potassium hydroxide (KOH) smear and fungal culture examination
      of tinea pedis. Objective. To evaluate the sensitivity and specificity of KOH
      smear and fungal culture for diagnosing tinea pedis. Methods. A pooled analysis
      of data from five similarly conducted bioequivalence trials for antifungal drugs
      was performed. Data from 460 patients enrolled in the vehicle arms of these
      studies with clinical diagnosis of tinea pedis supported by positive fungal
      culture were analyzed 6 weeks after initiation of the study to determine the
      sensitivity and specificity of KOH smear and fungal culture. Results. Using
      clinical assessment as the gold standard, the sensitivities for KOH smear and
      culture were 73.3% (95% CI: 66.3 to 79.5%) and 41.7% (34.6 to 49.1%),
      respectively. The respective specificities for culture and KOH smear were 77.7%
      (72.2 to 82.5%) and 42.5% (36.6 to 48.6%). Conclusion. KOH smear and fungal
      culture are complementary diagnostic tests for tinea pedis, with the former being
      the more sensitive test of the two, and the latter being more specific.

PMID- 20672003
TI  - Adipocytes as an Important Source of Serum S100B and Possible Roles of This
      Protein in Adipose Tissue.
AB  - Adipocytes contain high levels of S100B and in vitro assays indicate a modulated
      secretion of this protein by hormones that regulate lipolysis, such as glucagon,
      adrenaline, and insulin. A connection between lipolysis and S100B release has
      been proposed but definitive evidence is lacking. Although the biological
      significance of extracellular S100B from adipose tissue is still unclear, it is
      likely that this tissue might be an important source of serum S100B in situations
      related, or not, to brain damage. Current knowledge does not preclude the use of
      this protein in serum as a marker of brain injury or astroglial activation, but
      caution is recommended when discussing the significance of changes in serum
      levels where S100B may function as an adipokine, a neurotrophic cytokine, or an
      alarmin.

PMID- 20672005
TI  - Iron chelation therapy in myelodysplastic syndromes.
AB  - Myelodysplastic syndromes (MDS) are a heterogeneous disorder of the hematopoietic
      stem cells, frequently characterized by anemia and transfusion dependency. In low
      risk patients, transfusion dependency can be long lasting, leading to iron
      overload. Iron chelation therapy may be a therapeutic option for these patients,
      especially since the approval of oral iron chelators, which are easier to use and
      better accepted by the patients. The usefulness of iron chelation in MDS patients
      is still under debate, mainly because of the lack of solid prospective clinical
      trials that should take place in the future. This review aims to summarize what
      is currently known about the incidence and clinical consequences of iron overload
      in MDS patients and the state-of the-art of iron chelation therapy in this
      setting. We also give an overview of clinical guidelines for chelation in MDS
      published to date and some perspectives for the future.

PMID- 20672006
TI  - Totally Laparoscopic Gastrectomy for Gastric Cancer Associated with
      Recklinghausen's Disease.
AB  - This paper documents the first case of gastric cancer associated with
      Recklinghausen's disease, which was successfully treated by a totally
      laparoscopic operation. A 67-year-old woman with Recklinghausen's disease was
      referred to this department to undergo surgical treatment for early gastric
      cancer. The physical examination showed multiple cutaneous neurofibromas
      throughout the body surface, which made an upper abdominal incision impossible.
      Laparoscopic surgery requiring only small incisions was well indicated, and a
      totally laparoscopic distal gastrectomy with lymph node dissection was performed.
      Billroth I reconstruction was done intra-abdominally using a delta-shaped
      anastomosis. The patient followed a satisfactory postoperative course with no
      complications. Since the totally laparoscopic gastrectomy has many advantages
      over open surgery, it should therefore be preferentially used as a less invasive
      treatment in the field of gastric cancer.

PMID- 20672007
TI  - Benefits of neuropsychiatric phenomics: example of the 5-lipoxygenase-leptin
      Alzheimer connection.
AB  - Phenomics is a systematic study of phenotypes on a genomewide scale that is
      expected to unravel, as of yet, unsuspected functional roles of the genome. It
      remains to be determined how to optimally approach and analyze the available
      phenomics databases to spearhead innovation in neuropsychiatry. By
      serendipitously connecting two unrelated phenotypes of increased blood levels of
      the adipokine leptin, a molecule that regulates appetite, in 5-lipoxygenase- (5
      LOX) deficient mice and patients with a lower risk for Alzheimer's disease (AD),
      we postulated a leptin-mediated basis for beneficial effects of ALOX5 (a gene
      encoding 5-LOX) gene-deficiency in AD. We suggest that it might be possible to
      avoid relying on serendipity and develop data-mining tools capable of extracting
      from phenomics databases indications for such novel hypotheses. Hence, we provide
      an example of using a free-access Arrowsmith two-node search interface to
      identify ALOX5 as unsuspected putative mechanisms for the previously described
      clinical association between increased plasma levels of leptin and a lower risk
      of incident dementia and AD.

PMID- 20672008
TI  - Recurrent urinary bladder paraganglioma.
AB  - A 39-year-old male presented with recurrent attacks of painless haematuria. The
      patient has a history of partial cystectomy for bladder paraganglioma 10 years
      prior to the presentation. Imaging study and cystoscopic examination revealed a
      small anterior wall bladder tumor. The histological examination of the lesion
      confirmed that it was a urinary paraganglioma. Partial cystectomy was performed
      to this recurrent lesion. This case report stresses the importance of life-long
      follow-up of these lesions.

PMID- 20672009
TI  - The determination of melanoma stage at diagnosis.
AB  - The rising proportion of melanomas diagnosed at an early pathologic stage is
      commonly ascribed to better public education. However in the US SEER program of
      cancer registration it has been found that the rates for in situ melanomas are
      closely related by a log linear relationship to the incidence of invasive
      melanomas and that this relationship is unrelated to calendar year or gender or
      patient age. This relationship is sufficiently strong to leave little room for
      other factors. The relationship may be different in populations with different
      melanoma rates and responses to them. It is suggested that the results are due to
      variations within populations of individual response to melanoma cell
      proliferation.

PMID- 20672010
TI  - Single-Port Laparoscopy, NOTES, and Endoluminal Surgery.

PMID- 20672011
TI  - Exploring the Nature of Desmosomal Cadherin Associations in 3D.
AB  - Desmosomes are a complex assembly of protein molecules that mediate adhesion
      between adjacent cells. Desmosome composition is well established and spatial
      relationships between components have been identified. Intercellular cell-cell
      adhesion is created by the interaction of extracellular domains of desmosomal
      cadherins, namely, desmocollins and desmogleins. High-resolution methods have
      provided insight into the structural interactions between cadherins. However,
      there is a lack of understanding about the architecture of the intact desmosomes
      and the physical principles behind their adhesive strength are unclear. Electron
      Tomography (ET) studies have offered three-dimensional visual data of desmosomal
      cadherin associations at molecular resolution. This review discusses the merits
      of two cadherin association models represented using ET. We discuss the possible
      role of sample preparation on the structural differences seen between models and
      the possibility of adaptive changes in the structure as a direct consequence of
      mechanical stress and stratification.

PMID- 20672013
TI  - Buffers of Racial Discrimination: Links with Depression among Rural African
      American Mothers.
AB  - The current study examines racial discrimination as a predictor of depression in
      a sample of 414 rural, low-income African American mothers of young children. The
      potential moderating role of optimism and church-based social support was also
      examined. Mothers completed questionnaires when their child was 24-months-old.
      Hierarchical regression revealed that mothers' perception of racism was a
      significant predictor of depression even after controlling for a variety of
      distal demographic characteristics and environmental stressors. Significant
      interactions suggested the importance of psychological and social characteristics
      in understanding maternal depression. Specifically, high levels of optimism and
      church-based social support buffered mothers from increased depressive
      symptomology due to perceived racism.

PMID- 20672014
TI  - Formal total synthesis of (+/-)-cortistatin A.
AB  - A second-generation synthesis of the pentacyclic core of the cortistatins, a
      family of rearranged steroidal alkaloids that have recently attracted much
      attention, is reported. The improved sequence provides access to significant
      quantities of this key compound, which enabled a formal total synthesis of (+/-)
      cortistatin A by conversion to the key Nicolaou/Hirama dienone. It is anticipated
      that this new, robust route to the pentacyclic core will facilitate the total
      synthesis of a range of natural products in the cortistatin family, as well as
      the construction of key structural analogs to probe the promising biological
      activity of these important compounds.

PMID- 20672012
TI  - Probiotics-host communication: Modulation of signaling pathways in the intestine.
AB  - The intestinal microbiota includes a diverse group of functional microorganisms,
      including candidate probiotics or viable microorganisms that benefit the host.
      Beneficial effects of probiotics include enhancing intestinal epithelial cell
      function, protecting against physiologic stress, modulating cytokine secretion
      profiles, influencing T lymphocyte populations, and enhancing antibody secretion.
      Probiotics have demonstrated significant potential as therapeutic options for a
      variety of diseases, but the mechanisms responsible for these effects remain to
      be fully elucidated. Accumulating evidence demonstrates that probiotics
      communicate with the host by modulating key signaling pathways, such as NFkappaB
      and MAPK, to either enhance or suppress activation and influence downstream
      pathways. Beneficial microbes can profoundly alter the physiology of the
      gastrointestinal tract, and understanding these mechanisms may result in new
      diagnostic and therapeutic strategies.

PMID- 20672015
TI  - COGNITIVE DECLINE IN A DOG MODEL FOR AN INHERITED NEURODEGENERATIVE DISEASE USING
      T-MAZE PERFORMANCE.

PMID- 20672016
TI  - A Branched DNA Assay for Detecting TMPRSS2-ERG Fusions.

PMID- 20672017
TI  - A Phosphotyrosine Proteomic Screen Identifies Multiple Tyrosine Kinase Signaling
      Pathways Aberrantly Activated in Malignant Mesothelioma.
AB  - Malignant mesothelioma (MM) is a highly aggressive cancer that is refractory to
      all current chemotherapeutic regimens. Therefore, uncovering new rational
      therapeutic targets is imperative in the field. Tyrosine kinase signaling
      pathways are aberrantly activated in many human cancers and are currently being
      targeted for chemotherapeutic intervention. Thus, we sought to identify tyrosine
      kinases hyperactivated in MM. An unbiased phosphotyrosine proteomic screen was
      employed to identify tyrosine kinases activated in human MM cell lines. From this
      screen, we have identified novel signaling molecules, such as JAK1, STAT1,
      cortactin (CTTN), FER, p130Cas (BCAR1), SRC and FYN as tyrosine phosphorylated in
      human MM cell lines. Additionally, STAT1 and SRC family kinases (SFK) were
      confirmed to be active in primary MM specimens. We also confirmed that known
      signal transduction pathways previously implicated in MM, such as EGFR and MET
      signaling axes, are co-activated in the majority of human MM specimens and cell
      lines tested. EGFR, MET, and SFK appear to be co-activated in a significant
      proportion of MM cell lines, and dual inhibition of these kinases was
      demonstrated to be more efficacious for inhibiting MM cell viability and
      downstream effector signaling than inhibition of a single tyrosine kinase.
      Consequently, these data suggest that TKI mono-therapy may not represent an
      efficacious strategy for the treatment of MM, due to multiple tyrosine kinases
      potentially signaling redundantly to cellular pathways involved in tumor cell
      survival and proliferation.

PMID- 20672018
TI  - Recent sex trade and injection drug use among pregnant opiate and cocaine
      dependent women in treatment: The significance of psychiatric comorbidity.
AB  - OBJECTIVES: This study examined whether opioid and cocaine dependent pregnant
      women with psychiatric comorbidity were at elevated risk for infectious disease
      by virtue of recent sex trade and injection drug use that overlapped with
      pregnancy. We hypothesized that opioid and cocaine dependent women with
      psychiatric comorbidity would have greater odds for engaging in recent sex trade
      and injection drug use. METHODS: Eighty-one, HIV-seronegative pregnant women
      (59.3% African-American, 37% white, and 3.7% other) who were enrolled in drug
      treatment in Baltimore, Maryland were recruited into an HIV prevention
      intervention study, provided informed consent, and attended an in-person,
      baseline assessment administered by trained clinicians. Assessments included the
      The Structured Clinical Interview for DSM-IV-TR Axis I Disorders, the HIV Risk
      Behavior Interview, and a demographic questionnaire. The majority of women had
      lifetime histories of opioid and/or cocaine dependence (93.8%) and those with an
      additional lifetime non-substance-related Axis I disorder comprised the
      psychiatric comorbidity group. RESULTS: Thirty-percent reported recent sex trade
      and/or injection drug use that overlapped with pregnancy. While psychiatric
      comorbidity was associated with 6 times the odds of opioid and cocaine dependent
      pregnant women having recently traded sex it was not associated with recent
      injection drug use. CONCLUSIONS: Findings underscore the need to (1) treat
      comorbid psychiatric disorders among pregnant women in treatment for cocaine and
      opioid dependence and (2) integrate HIV prevention interventions into drug
      dependence treatment for pregnant women, particularly those with psychiatric
      comorbidity given their elevated risk for infectious disease.

PMID- 20672019
TI  - Latent Transition Analysis: Benefits of a Latent Variable Approach to Modeling
      Transitions in Substance Use.
AB  - We apply latent transition analysis (LTA) to characterize transitions over time
      in substance use behavior profiles among first-year college students. Advantages
      of modeling substance use behavior as a categorical latent variable are
      demonstrated. Alcohol use (any drinking and binge drinking), cigarette use, and
      marijuana use were assessed in a sample (N=718) of college students during the
      fall and spring semesters. Four profiles of 14-day substance use behavior were
      identified: (1) Non-Users; (2) Cigarette Smokers; (3) Binge Drinkers; and (4)
      Bingers with Marijuana Use. The most prevalent behavior profile at both times was
      the Non-Users (with over half of the students having this profile), followed by
      Binge Drinkers and Bingers with Marijuana Use. Cigarette Smokers was the least
      prevalent behavior profile. Gender, race/ethnicity, early onset of alcohol use,
      grades in high school, membership in the honors program, and friendship goals
      were all significant predictors of substance use behavior profile.

PMID- 20672020
TI  - Musculoskeletal pain and measures of depression: response to comment on the
      article by Poleshuck et al.

PMID- 20672021
TI  - Using Exploratory Focus Groups to Inform the Development of Targeted COPD Self
      Management Education DVDs for Rural Patients.
AB  - This exploratory study assessed the self-management learning needs, experiences,
      and perspectives of COPD patients treated at a Certified Federal Rural Health
      Clinic to inform the development of a COPD self-management DVD. A purposive,
      homogeneous sample of COPD patients participated in focus group interviews. Data
      from these interviews were referenced to edit a library of Rvision COPD self
      management DVDs into a single condensed DVD containing only the most pertinent
      self-management topics. Patients reported a lack of knowledge and skill
      development related to purse lipped breathing, controlled coughing, and stress
      management; while medication management skills were found to be quite adequate.
      Engaging rural communities in formal qualitative inquiries to describe COPD
      specific needs for self-management may lead to future use of educational
      technologies aimed at improving quality of life for these rural, hard to reach
      populations.

PMID- 20672022
TI  - Genetic Influences on Individual Differences in Exercise Behavior during
      Adolescence.
AB  - The aim of this study was to investigate the degree to which genetic and
      environmental influences affect variation in adolescent exercise behavior. Data
      on regular leisure time exercise activities were analyzed in 8,355 adolescent
      twins, from three-age cohorts (13-14, 15-16, and 17-19 years). Exercise behavior
      was assessed with survey items about type of regular leisure time exercise,
      frequency, and duration of the activities. Participants were classified as
      sedentary, regular exercisers, or vigorous exercisers. The prevalence of moderate
      exercise behavior declined from age 13 to 19 years with a parallel increase in
      prevalence of sedentary behavior, whereas the prevalence of vigorous exercise
      behavior remained constant across age cohorts. Variation in exercise behavior was
      analyzed with genetic structural equation modeling employing a liability
      threshold model. Variation was largely accounted for by genetic factors (72% to
      85% of the variance was explained by genetic factors), whereas shared
      environmental factors only accounted for a substantial part of the variation in
      girls aged 13-14 years (46%). We hypothesize that genetic effects on exercise
      ability may explain the high heritability of exercise behavior in this phase of
      life.

PMID- 20672023
TI  - Intracellular and Extracellular Effects of S100B in the Cardiovascular Response
      to Disease.
AB  - S100B, a calcium-binding protein of the EF-hand type, exerts both intracellular
      and extracellular functions. S100B is induced in the myocardium of human subjects
      and an experimental rat model following myocardial infarction. Forced expression
      of S100B in neonatal rat myocyte cultures and high level expression of S100B in
      transgenic mice hearts inhibit cardiac hypertrophy and the associated phenotype
      but augments myocyte apoptosis following myocardial infarction. By contrast,
      knocking out S100B, augments hypertrophy, decreases apoptosis and preserves
      cardiac function following myocardial infarction. Expression of S100B in aortic
      smooth muscle cells inhibits cell proliferation and the vascular response to
      adrenergic stimulation. S100B induces apoptosis by an extracellular mechanism via
      interaction with the receptor for advanced glycation end products and activating
      ERK1/2 and p53 signaling. The intracellular and extracellular roles of S100B are
      attractive therapeutic targets for the treatment of both cardiac and vascular
      diseases.

PMID- 20672024
TI  - Impact of medical therapy on atheroma volume measured by different cardiovascular
      imaging modalities.
AB  - Atherosclerosis is a systemic disease that affects most vascular beds. The gold
      standard of atherosclerosis imaging has been invasive intravascular ultrasound
      (IVUS). Newer noninvasive imaging modalities like B-mode ultrasound, cardiac
      computed tomography (CT), positron emission tomography (PET), and magnetic
      resonance imaging (MRI) have been used to assess these vascular territories with
      high accuracy and reproducibility. These imaging modalities have lately been used
      for the assessment of the atherosclerotic plaque and the response of its volume
      to several medical therapies used in the treatment of patients with
      cardiovascular disease. To study the impact of these medications on atheroma
      volume progression or regression, imaging modalities have been used on a serial
      basis providing a unique opportunity to monitor the effect these
      antiatherosclerotic strategies exert on plaque burden. As a result, studies
      incorporating serial IVUS imaging, quantitative coronary angiography (QCA), B
      mode ultrasound, electron beam computed tomography (EBCT), and dynamic contrast
      enhanced magnetic resonance imaging have all been used to evaluate the impact of
      therapeutic strategies that modify cholesterol and blood pressure on the
      progression/regression of atherosclerotic plaque. In this review, we intend to
      summarize the impact of different therapies aimed at halting the progression or
      even result in regression of atherosclerotic cardiovascular disease evaluated by
      different imaging modalities.

PMID- 20672025
TI  - Progression analysis and stage discovery in continuous physiological processes
      using image computing.
AB  - We propose an image computing-based method for quantitative analysis of
      continuous physiological processes that can be sensed by medical imaging and
      demonstrate its application to the analysis of morphological alterations of the
      bone structure, which correlate with the progression of osteoarthritis (OA). The
      purpose of the analysis is to quantitatively estimate OA progression in a fashion
      that can assist in understanding the pathophysiology of the disease. Ultimately,
      the texture analysis will be able to provide an alternative OA scoring method,
      which can potentially reflect the progression of the disease in a more direct
      fashion compared to the existing clinically utilized classification schemes based
      on radiology. This method can be useful not just for studying the nature of OA,
      but also for developing and testing the effect of drugs and treatments. While in
      this paper we demonstrate the application of the method to osteoarthritis, its
      generality makes it suitable for the analysis of other progressive clinical
      conditions that can be diagnosed and prognosed by using medical imaging.

PMID- 20672026
TI  - Facile Synthesis and Tensile Behavior of TiO(2) One-Dimensional Nanostructures.
AB  - High-yield synthesis of TiO(2) one-dimensional (1D) nanostructures was realized
      by a simple annealing of Ni-coated Ti grids in an argon atmosphere at 950 degrees
      C and 760 torr. The as-synthesized 1D nanostructures were single crystalline
      rutile TiO(2) with the preferred growth direction close to [210]. The growth of
      these nanostructures was enhanced by using catalytic materials, higher reaction
      temperature, and longer reaction time. Nanoscale tensile testing performed on
      individual 1D nanostructures showed that the nanostructures appeared to fracture
      in a brittle manner. The measured Young's modulus and fracture strength are ~56.3
      and 1.4 GPa, respectively.

PMID- 20672027
TI  - A new extension of cauchy-born rule for monolayer crystal films.
AB  - By combining with the physical concept of inscribed surface, the standard Cauchy
      Born rule (CBR) is straightly extended to have a rigorous and accurate atomistic
      continuum theory for the monolayer crystal films. Resorting to using Tersoff
      Brenner potential, the present theory to graphite sheet and single-walled carbon
      nanotubes (SWCNTs) is applied to evaluate the mechanical properties. The results
      are validated by the comparison with previously reported studies.

PMID- 20672028
TI  - Snap-Through Instability of Graphene on Substrates.
AB  - We determine the graphene morphology regulated by substrates with herringbone and
      checkerboard surface corrugations. As the graphene-substrate interfacial bonding
      energy and the substrate surface roughness vary, the graphene morphology snaps
      between two distinct states: (1) closely conforming to the substrate and (2)
      remaining nearly flat on the substrate. Since the graphene morphology is strongly
      tied to the electronic properties of graphene, such a snap-through instability of
      graphene morphology can lead to desirable graphene electronic properties that
      could potentially enable graphene-based functional electronic components (e.g.
      nano-switches).

PMID- 20672029
TI  - Seedless Pattern Growth of Quasi-Aligned ZnO Nanorod Arrays on Cover Glass
      Substrates in Solution.
AB  - A hybrid technique for the selective growth of ZnO nanorod arrays on wanted
      areas of thin cover glass substrates was developed without the use of seed layer
      of ZnO. This method utilizes electron-beam lithography for pattern transfer on
      seedless substrate, followed by solution method for the bottom-up growth of ZnO
      nanorod arrays on the patterned substrates. The arrays of highly crystalline ZnO
      nanorods having diameter of 60 +/- 10 nm and length of 750 +/- 50 nm were
      selectively grown on different shape patterns and exhibited a remarkable
      uniformity in terms of diameter, length, and density. The room temperature
      cathodluminescence measurements showed a strong ultraviolet emission at 381 nm
      and broad visible emission at 585-610 nm were observed in the spectrum.

PMID- 20672030
TI  - One-Pot Green Synthesis and Bioapplication ofl-Arginine-Capped Superparamagnetic
      Fe3O4 Nanoparticles.
AB  - Water-solublel-arginine-capped Fe3O4 nanoparticles were synthesized using a one
      pot and green method. Nontoxic, renewable and inexpensive reagents including
      FeCl3,l-arginine, glycerol and water were chosen as raw materials. Fe3O4
      nanoparticles show different dispersive states in acidic and alkaline solutions
      for the two distinct forms of surface bindingl-arginine. Powder X-ray diffraction
      and X-ray photoelectron spectroscopy were used to identify the structure of Fe3O4
      nanocrystals. The products behave like superparamagnetism at room temperature
      with saturation magnetization of 49.9 emu g-1 and negligible remanence or
      coercivity. In the presence of 1-ethyl-3-(dimethylaminopropyl) carbodiimide
      hydrochloride, the anti-chloramphenicol monoclonal antibodies were connected to
      thel-arginine-capped magnetite nanoparticles. The as-prepared conjugates could be
      used in immunomagnetic assay.(See supplementary material 1).

PMID- 20672031
TI  - Preparation and characterization of fluorescence probe from assembly
      hydroxyapatite nanocomposite.
AB  - A new nanocomposite fluorescence probe with thioglycolic acid (TA) functional
      layers embedded inside the hydroxyapatite nanoribbon spherulites has been
      synthesized. The fluorescence intensity of the novel probe is about 1.5-3.3-fold
      increase compared with the probe containing no TA. When used to detect cadmium
      ion, the most of original assembly nanoribbon spherulites structure in the novel
      probe is found to have been damaged to new flake structures. The mechanism of
      determining cadmium ion in alcohol solution has been studied. The present
      systematic study provides significant information on the effect of assembly
      nanostructure on the metal-enhanced fluorescence phenomenon.

PMID- 20672032
TI  - Nanoparticulate PdZn as a Novel Catalyst for ZnO Nanowire Growth.
AB  - ZnO nanowires have been grown by chemical vapour deposition (CVD) using PdZn
      bimetallic nanoparticles to catalyse the process. Nanocatalyst particles with
      mean particle diameters of 2.6 +/- 0.3 nm were shown to catalyse the growth
      process, displaying activities that compare well with those reported for
      sputtered systems. Since nanowire diameters are linked to catalyst morphology,
      the size-control we are able to exhibit during particle preparation represents an
      advantage over existing approaches in terms of controlling nanowire dimensions,
      which is necessary in order to utilize the nanowires for catalytic or electrical
      applications.(See supplementary material 1).

PMID- 20672033
TI  - Controllable Synthesis of Single-Crystalline CdO and Cd(OH)2Nanowires by a Simple
      Hydrothermal Approach.
AB  - Single-crystalline Cd(OH)2 or CdO nanowires can be selectively synthesized at
      150  degrees C by a simple hydrothermal method using aqueous Cd(NO3)2 as
      precursor. The method is biosafe, and compared to the conventional oil-water
      surfactant approach, more environmental-benign. As revealed by the XRD results,
      CdO or Cd(OH)2 nanowires can be generated in high purity by varying the time of
      synthesis. The results of FESEM and HRTEM analysis show that the CdO nanowires
      are formed in bundles. Over the CdO-nanowire bundles, photoluminescence at ~517
      nm attributable to near band-edge emission of CdO was recorded. Based on the
      experimental results, a possible growth mechanism of the products is proposed.

PMID- 20672034
TI  - Copper selenide nanosnakes: bovine serum albumin-assisted room temperature
      controllable synthesis and characterization.
AB  - Herein we firstly reported a simple, environment-friendly, controllable
      synthetic method of CuSe nanosnakes at room temperature using copper salts and
      sodium selenosulfate as the reactants, and bovine serum albumin (BSA) as foaming
      agent. As the amounts of selenide ions (Se2-) released from Na2SeSO3 in the
      solution increased, the cubic and snake-like CuSe nanostructures were formed
      gradually, the cubic nanostructures were captured by the CuSe nanosnakes, the
      CuSe nanosnakes grew wider and longer as the reaction time increased. Finally,
      the cubic CuSe nanostructures were completely replaced by BSA-CuSe nanosnakes.
      The prepared BSA-CuSe nanosnakes exhibited enhanced biocompatibility than the
      CuSe nanocrystals, which highly suggest that as-prepared BSA-CuSe nanosnakes have
      great potentials in applications such as biomedical engineering.

PMID- 20672035
TI  - Cooperative Effects in the Photoluminescence of (In,Ga)As/GaAs Quantum Dot Chain
      Structures.
AB  - Multilayer In0.4Ga0.6As/GaAs quantum dot (QD) chain samples are investigated by
      means of cw and time-resolved photoluminescence (PL) spectroscopy in order to
      study the peculiarities of interdot coupling in such nanostructures. The
      temperature dependence of the PL has revealed details of the confinement. Non
      thermal carrier distribution through in-chain, interdot wave function coupling is
      found. The peculiar dependences of the PL decay time on the excitation and
      detection energies are ascribed to the electronic interdot coupling and the long
      range coupling through the radiation field. It is shown that the dependence of
      the PL decay time on the excitation wavelength is a result of the superradiance
      effect.

PMID- 20672036
TI  - Residual Stress Relaxation Induced by Mass Transport Through Interface of the
      Pd/SrTiO3.
AB  - Metal interconnections having a small cross-section and short length can be
      subjected to very large mass transport due to the passing of high current
      densities. As a result, nonlinear diffusion and electromigration effects which
      may result in device failure and electrical instabilities may be manifested.
      Various thicknesses of Pd were deposited over SrTiO3 substrate. Residual stress
      of the deposited film was evaluated by measuring the variation of d-spacing
      versus sin2psi through conventional X-ray diffraction method. It has been found
      that the lattice misfit within film and substrate might be relaxed because of
      mass transport. Besides, the relation between residual intrinsic stress and
      oxygen diffusion through deposited film has been expressed. Consequently,
      appearance of oxide intermediate layer may adjust interfacial characteristics and
      suppress electrical conductivity by increasing electron scattering through
      metallic films.

PMID- 20672037
TI  - Protein functionalized nanodiamond arrays.
AB  - Various nanoscale elements are currently being explored for bio-applications,
      such as in bio-images, bio-detection, and bio-sensors. Among them, nanodiamonds
      possess remarkable features such as low bio-cytotoxicity, good optical property
      in fluorescent and Raman spectra, and good photostability for bio-applications.
      In this work, we devise techniques to position functionalized nanodiamonds on
      self-assembled monolayer (SAMs) arrays adsorbed on silicon and ITO substrates
      surface using electron beam lithography techniques. The nanodiamond arrays were
      functionalized with lysozyme to target a certain biomolecule or protein
      specifically. The optical properties of the nanodiamond-protein complex arrays
      were characterized by a high throughput confocal microscope. The synthesized
      nanodiamond-lysozyme complex arrays were found to still retain their
      functionality in interacting with E. coli.

PMID- 20672038
TI  - Photovoltaic Properties of p-Doped GaAs Nanowire Arrays Grown on n-Type
      GaAs(111)B Substrate.
AB  - We report on the molecular beam epitaxy growth of Au-assisted GaAs p-type-doped
      NW arrays on the n-type GaAs(111)B substrate and their photovoltaic properties.
      The samples are grown at different substrate temperature within the range from
      520 to 580  degrees C. It is shown that the dependence of conversion efficiency
      on the substrate temperature has a maximum at the substrate temperature of 550 
      degrees C. For the best sample, the conversion efficiency of 1.65% and the fill
      factor of 25% are obtained.

PMID- 20672039
TI  - Investigation of a Mesoporous Silicon Based Ferromagnetic Nanocomposite.
AB  - A semiconductor/metal nanocomposite is composed of a porosified silicon wafer and
      embedded ferromagnetic nanostructures. The obtained hybrid system possesses the
      electronic properties of silicon together with the magnetic properties of the
      incorporated ferromagnetic metal. On the one hand, a transition metal is
      electrochemically deposited from a metal salt solution into the nanostructured
      silicon skeleton, on the other hand magnetic particles of a few nanometres in
      size, fabricated in solution, are incorporated by immersion. The
      electrochemically deposited nanostructures can be tuned in size, shape and their
      spatial distribution by the process parameters, and thus specimens with desired
      ferromagnetic properties can be fabricated. Using magnetite nanoparticles for
      infiltration into porous silicon is of interest not only because of the magnetic
      properties of the composite material due to the possible modification of the
      ferromagnetic/superparamagnetic transition but also because of the
      biocompatibility of the system caused by the low toxicity of both materials.
      Thus, it is a promising candidate for biomedical applications as drug delivery or
      biomedical targeting. 

PMID- 20672040
TI  - One-Step Synthesis of Monodisperse In-Doped ZnO Nanocrystals.
AB  - A method for the synthesis of high quality indium-doped zinc oxide (In-doped
      ZnO) nanocrystals was developed using a one-step ester elimination reaction based
      on alcoholysis of metal carboxylate salts. The resulting nearly monodisperse
      nanocrystals are well-crystallized with typically crystal structure identical to
      that of wurtzite type of ZnO. Structural, optical, and elemental analyses on the
      products indicate the incorporation of indium into the host ZnO lattices. The
      individual nanocrystals with cubic structures were observed in the 5% In-ZnO
      reaction, due to the relatively high reactivity of indium precursors. Our study
      would provide further insights for the growth of doped oxide nanocrystals, and
      deepen the understanding of doping process in colloidal nanocrystal syntheses.

PMID- 20672041
TI  - Optical Properties of GaAs Quantum Dots Fabricated by Filling of Self-Assembled
      Nanoholes.
AB  - Experimental results of the local droplet etching technique for the self
      assembled formation of nanoholes and quantum rings on semiconductor surfaces are
      discussed. Dependent on the sample design and the process parameters, filling of
      nanoholes in AlGaAs generates strain-free GaAs quantum dots with either broadband
      optical emission or sharp photoluminescence (PL) lines. Broadband emission is
      found for samples with completely filled flat holes, which have a very broad
      depth distribution. On the other hand, partly filling of deep holes yield highly
      uniform quantum dots with very sharp PL lines.

PMID- 20672042
TI  - Interaction and Cooperative Nucleation of InAsSbP Quantum Dots and Pits on
      InAs(100) Substrate.
AB  - An example of InAsSbP quaternary quantum dots (QDs), pits and dots-pits
      cooperative structures' growth on InAs(100) substrates by liquid phase epitaxy
      (LPE) is reported. The interaction and surface morphology of the dots-pits
      combinations are investigated by the high-resolution scanning electron
      microscope. Bimodal growth mechanism for the both QDs and pits nucleation is
      observed. Cooperative structures consist of the QDs banded by pits, as well as
      the "large" pits banded by the quantum wires are detected. The composition of the
      islands and the pits edges is found to be quaternary, enriched by antimony and
      phosphorus, respectively. This repartition is caused by dissociation of the
      wetting layer, followed by migration (surface diffusion) of the Sb and P atoms in
      opposite directions. The "small" QDs average density ranges from 0.8 to 2 * 109
      cm-2, with heights and widths dimensions from 2 to 20 nm and 5 to 45 nm,
      respectively. The average density of the "small" pits is equal to (6-10) * 109 cm
      2 with dimensions of 5-40 nm in width and depth. Lifshits-Slezov-like
      distribution for the amount and surface density of both "small" QDs and pits
      versus their average diameter is experimentally detected. A displacement of the
      absorption edge toward the long wavelength region and enlargement toward the
      short wavelength region is detected by the Fourier transform infrared
      spectrometry.

PMID- 20672043
TI  - One-Step UV-Induced Synthesis of Polypyrrole/Ag Nanocomposites at the Water/Ionic
      Liquid Interface.
AB  - Polpyrrole (PPy)/Ag nanocomposites were successfully synthesized at the
      interface of water and ionic liquid by one-step UV-induced polymerization. Highly
      dispersed PPy/Ag nanoparticles were obtained by controlling the experimental
      conditions. The results of Fourier-transform infrared spectroscopy, X-ray
      diffraction, transmission electron microscopy and X-ray photoelectron
      spectroscopy revealed that the UV-induced interface polymerization leaded to the
      formation of PPy incorporating silver nanoparticles. It was also found that the
      electrical conductivity of PPy/Ag nanocomposite was about 100 times higher than
      that of pure PPy.

PMID- 20672044
TI  - Multiscale simulation of indentation, retraction and fracture processes of
      nanocontact.
AB  - The process of nanocontact including indentation and retraction between a large
      Ni tip and a Cu substrate is investigated using quasicontinuum (QC) method. The
      multiscale model reveals that significant plastic deformation occurs during the
      process of nanocontact between Ni tip and Cu substrate. Plastic deformation is
      observed in an area as large as 20 nm wide and 10 nm thick beneath Ni tip during
      the indentation and retraction. Also, plastic deformation at a deep position in
      the Cu substrate does not disappear after the neck failure. The analysis of
      generalized planar fault energy curve shows that there is a strong tendency for
      deformation twinning in Cu substrate. However, deformation twinning will be
      retarded during indentation due to the high stress intensity caused by stepped
      surface of Ni tip. The abrupt drop of load curve during tip retraction is
      attributed to the two different fracture mechanisms. One is atomic rearrangement
      near the interface of Ni tip and Cu substrate at the initial stage of neck
      fracture, the other is shear behavior of adjacent {111} planes at the necking
      point. A comparison of the critical load and critical contact radius for neck
      fracture is also made between theoretical values and our numerical results.

PMID- 20672045
TI  - Biomolecular nano-flow-sensor to measure near-surface flow.
AB  - We have proposed and experimentally demonstrated that the measurement of the
      near-surface flow at the interface between a liquid and solid using a 10 nm-sized
      biomolecular motor of F1-ATPase as a nano-flow-sensor. For this purpose, we
      developed a microfluidic test-bed chip to precisely control the liquid flow
      acting on the F1-ATPase. In order to visualize the rotation of F1-ATPase, several
      hundreds nanometer-sized particle was immobilized at the rotational axis of F1
      ATPase to enhance the rotation to be detected by optical microscopy. The
      rotational motion of F1-ATPase, which was immobilized on an inner surface of the
      test-bed chip, was measured to obtain the correlation between the near-surface
      flow and the rotation speed of F1-ATPase. As a result, we obtained the
      relationship that the rotation speed of F1-ATPase was linearly decelerated with
      increasing flow velocity. The mechanism of the correlation between the rotation
      speed and the near-surface flow remains unclear, however the concept to use
      biomolecule as a nano-flow-sensor was proofed successfully.(See supplementary
      material 1).

PMID- 20672046
TI  - Synthesis and Cytotoxicity of Y(2)O(3) Nanoparticles of Various Morphologies.
AB  - As the field of nanotechnology continues to grow, evaluating the cytotoxicity of
      nanoparticles is important in furthering their application within biomedicine.
      Here, we report the synthesis, characterization, and cytotoxicity of
      nanoparticles of different morphologies of yttrium oxide, a promising material
      for biological imaging applications. Nanoparticles of spherical, rod-like, and
      platelet morphologies were synthesized via solvothermal and hydrothermal methods
      and characterized by transmission electron microscopy (TEM), X-ray diffraction
      (XRD), light scattering, surface area analysis, thermogravimetric analysis (TGA),
      and zeta potential measurements. Nanoparticles were then tested for cytotoxicity
      with human foreskin fibroblast (HFF) cells, with the goal of elucidating
      nanoparticle characteristics that influence cytotoxicity. Cellular response was
      different for the different morphologies, with spherical particles exhibiting no
      cytotoxicity to HFF cells, rod-like particles increasing cell proliferation, and
      platelet particles markedly cytotoxic. However, due to differences in the
      nanoparticle chemistry as determined through the characterization techniques, it
      is difficult to attribute the cytotoxicity responses to the particle morphology.
      Rather, the cytotoxicity of the platelet sample appears due to the stabilizing
      ligand, oleylamine, which was present at higher levels in this sample. This study
      demonstrates the importance of nanoparticle chemistry on in vitro cytotoxicity,
      and highlights the general importance of thorough nanoparticle characterization
      as a prerequisite to understanding nanoparticle cytotoxicity.

PMID- 20672048
TI  - Life-threatening adenovirus infections in the setting of the immunocompromised
      allogeneic stem cell transplant patients.
AB  - A single institution case series of adenovirus infections after allogeneic
      hematopoietic stem cell transplantation is presented to highlight the
      consideration for adenovirus infections as an etiology in patients with rapid
      hepatic or other sudden organ deterioration in the setting of apparent GVHD
      stabilization. The series also highlights that survival is limited with these
      infections often due in part to concomitant opportunistic infections. In
      addition, the pathophysiological events, such as GVHD and hepatic dysfunction,
      may complicate the clinical picture and delay therapy of an opportunistic
      infection. This is particularly true for adenoviral infections as they also have
      a distinct clinical picture in immunocompromised patients when compared to immune
      competent patients. Adenovirus infections also have the additional challenge that
      its treatment, cidofovir, has associated toxicities that can delay its
      administration. Recent developments has yielded an assay that can be used in the
      early detection and for serial determinations of adenovirus in patients with
      advanced GVHD, as well as a new therapeutic agent currently undergoing clinical
      trials.

PMID- 20672047
TI  - The battle between virus and host: modulation of Toll-like receptor signaling
      pathways by virus infection.
AB  - In order to establish an infection, viruses need to either suppress or escape
      from host immune defense systems. Recent immunological research has focused on
      innate immunity as the first line of host defense, especially pattern recognition
      molecules such as Toll-like receptors (TLRs), RIG-I-like receptors (RLRs), and
      NOD-like receptors (NLRs). Various microbial components are recognized by their
      vague and common molecular shapes so-called, pathogen-associated molecular
      patterns (PAMPs). PAMPs induce inflammatory reactions mediated by the activation
      of the transcription factor, NF-kappaB, and by interferons, which lead to an
      antiviral immune response. Viruses have the capacity to suppress or escape from
      this pattern recognition molecule-mediated antimicrobial response in various
      ways. In this paper, we review the various strategies used by viruses to modulate
      the pattern recognition molecule-mediated innate immune response.

PMID- 20672049
TI  - Unexplained Graft Dysfunction after Heart Transplantation-Role of Novel Molecular
      Expression Test Score and QTc-Interval: A Case Report.
AB  - In the current era of immunosuppressive medications there is increased observed
      incidence of graft dysfunction in the absence of known histological criteria of
      rejection after heart transplantation. A noninvasive molecular expression
      diagnostic test was developed and validated to rule out histological acute
      cellular rejection. In this paper we present for the first time, longitudinal
      pattern of changes in this novel diagnostic test score along with QTc-interval in
      a patient who was admitted with unexplained graft dysfunction. Patient presented
      with graft failure with negative findings on all known criteria of rejection
      including acute cellular rejection, antibody mediated rejection and cardiac
      allograft vasculopathy. The molecular expression test score showed gradual
      increase and QTc-interval showed gradual prolongation with the gradual decline in
      graft function. This paper exemplifies that in patients presenting with
      unexplained graft dysfunction, GEP test score and QTc-interval correlate with the
      changes in the graft function.

PMID- 20672050
TI  - Epidermal growth factor receptor tyrosine kinase inhibitors for elderly patients
      with advanced non-small cell lung cancer.
AB  - Lung cancer is the leading cause of cancer-related mortality in both men and
      women and approximately 219,440 new cases of nonsmall cell lung cancer (NSCLC)
      were estimated to occur in the USA in 2009, which caused 159,390 NSCLC-related
      deaths. More than 50% of cases of advanced NSCLC are diagnosed in patients older
      than age 65, and recent Surveillance Epidemiology and End Results (SEERs) data
      suggest that the median age at diagnosis is 70 years. Until recently, the disease
      has been undertreated in this patient population, with a perception among many
      clinicians that elderly patients do not tolerate chemotherapy or radiotherapy.
      So, single agent chemotherapy is the recommended approach by the ASCO and
      International Expert Panels in unselected patients. The introduction of novel
      targeted therapies, such as Epidermal Growth Factor Receptor (EGFR) Tyrosine
      Kinase Inhibitors (TKIs) which improved survival versus placebo in patients who
      had previously failed on chemotherapy, gives clinicians new, effective, and
      better tolerated options to consider when treating NSCLC in elderly patients.
      This paper describes the advances of EGFR TKIs for elderly patients with advanced
      NSCLC.

PMID- 20672052
TI  - Primary squamous cell carcinoma of the urinary bladder presenting as peritoneal
      carcinomatosis.
AB  - We report an unusual case of a 78-year-old Caucasian female, who presented with
      peritoneal carcinomatosis and hypercalcemia, and was found to have a rapidly
      progressive primary squamous cell carcinoma of the urinary bladder. Squamous cell
      bladder carcinoma is a rare malignancy in the United States, accounting for just
      1-3% of bladder tumors. Interestingly our patient lacked the established risk
      factors, including exposure to the parasite Schistosoma haematobium, recurrent
      urinary tract infections, bladder calculi, radiation exposure, chronic indwelling
      catheter, neurogenic bladder, or tobacco abuse. Although hypercalcemia has been
      rarely described, an initial presentation of peritioneal carcinomatosis has not
      been previously reported.

PMID- 20672051
TI  - The S100B/RAGE Axis in Alzheimer's Disease.
AB  - Increasing evidence suggests that the small EF-hand calcium-binding protein S100B
      plays an important role in Alzheimer's disease. Among other evidences are the
      increased levels of both S100B and its receptor, the Receptor for Advanced
      Glycation Endproducts (RAGEs) in the AD diseased brain. The regulation of RAGE
      signaling by S100B is complex and probably involves other ligands including the
      amyloid beta peptide (Abeta), the Advanced Glycation Endproducts (AGEs), or
      transtheyretin. In this paper we discuss the current literature regarding the
      role of S100B/RAGE activation in Alzheimer's disease.

PMID- 20672054
TI  - Asn and asn: critical residues for in vitro biological activity of reteplase.
AB  - Reteplase (rPA) is a thrombolytic agent used for the treatment of acute
      myocardial infarction. We studied the expression of rPA and its selected
      asparagine mutants after integration into the Pichia genome. Though methanol
      induction of the native and the rPA mutants showed similar expression levels
      (~200-250 mg/L), the mutants displayed significant loss of protease activity.
      Strikingly, the clot lysis activities of these mutants were considerably
      different. While mutation of Asn(12) (N12P) of the Kringle 2 domain showed
      delayed clot lysis activity (t(1/2) = 38 min) compared to the native rPA (t(1/2)
      = 33 min), a faster rate of clot lysis (t(1/2) = 27 min) was observed when the
      Asn(278) (N278S) of the serine protease domain was mutated. Interestingly, the
      slowest clot lysis activity (t(1/2) = 49 min) demonstrated by the double mutant
      (N12P, N278S) suggests the dominant role of Asn(12) in regulating the
      fibrinolytic activity of rPA. The results presented in this paper indicate that
      the fibrinolytic and the proteolytic activities of rPA are independent of each
      other.

PMID- 20672053
TI  - Archaea signal recognition particle shows the way.
AB  - Archaea SRP is composed of an SRP RNA molecule and two bound proteins named SRP19
      and SRP54. Regulated by the binding and hydrolysis of guanosine triphosphates,
      the RNA-bound SRP54 protein transiently associates not only with the hydrophobic
      signal sequence as it emerges from the ribosomal exit tunnel, but also interacts
      with the membrane-associated SRP receptor (FtsY). Comparative analyses of the
      archaea genomes and their SRP component sequences, combined with structural and
      biochemical data, support a prominent role of the SRP RNA in the assembly and
      function of the archaea SRP. The 5e motif, which in eukaryotes binds a 72
      kilodalton protein, is preserved in most archaea SRP RNAs despite the lack of an
      archaea SRP72 homolog. The primary function of the 5e region may be to serve as a
      hinge, strategically positioned between the small and large SRP domain, allowing
      the elongated SRP to bind simultaneously to distant ribosomal sites. SRP19,
      required in eukaryotes for initiating SRP assembly, appears to play a subordinate
      role in the archaea SRP or may be defunct. The N-terminal A region and a novel C
      terminal R region of the archaea SRP receptor (FtsY) are strikingly diverse or
      absent even among the members of a taxonomic subgroup.

PMID- 20672055
TI  - Relapsing polychondritis following alopecia areata.
AB  - A case of alopecia areata followed by relapsing polychondritis is presented.
      Similar cases from the literature are reviewed and speculation about the
      relationship of these diseases is offered. Although the occurrence of these
      diseases together could be coincidental, an association seems immunologically
      plausible. Thus, relapsing polychondritis might be an unusual systemic
      manifestation of alopecia areata.

PMID- 20672056
TI  - Probing aromaticity of borozene through optical and dielectric response: a
      theoretical study.
AB  - In this work, we report electronic structure calculations aimed at computing the
      linear optical absorption spectrum and static dipole polarizablity of a newly
      proposed boron-based planar aromatic compound borozene (B12H6). For the purpose,
      we use the semiempirical INDO model Hamiltonian, accompanied by large-scale
      correlation calculations using the multi-reference singles-doubles configuration
      interaction (MRSDCI) approach. We present detailed predictions about the
      energetics, polarization properties, and the nature of many-particle states
      contributing to various peaks in the linear absorption spectrum. Our results can
      be used to characterize this material in future optical absorption experiments.
      We also argue that one can deduce the aromaticity of the cluster from the optical
      absorption and static polarizability results.

PMID- 20672057
TI  - A New Method for Lift-off of III-Nitride Semiconductors for Heterogeneous
      Integration.
AB  - The release and transfer of GaN epilayers to other substrates is of interest for
      a variety of applications, including heterogeneous integration of silicon logic
      devices, III-V power devices and optical devices. We have developed a simple wet
      chemical etching method to release high-quality epitaxial III-nitride films from
      their substrates. This method builds on a nanoepitaxial lateral overgrowth (NELO)
      process that provides III-Nitride films with low dislocation densities. NELO is
      accomplished using a nanoporous mask layer patterned on GaN substrates. Chemical
      removal of the SiO2 layer after growth of III-Nitride overlayers causes fracture
      at the interface between the GaN film and the original GaN substrate, resulting
      in free-standing GaN films with nanostructured surfaces on one side. These layers
      can be transferred to other substrates, and the nano-structured surface can be
      used in photonic devices, or planarized for power devices.

PMID- 20672058
TI  - Solvothermal Synthesis of Ternary Sulfides of Sb2 - xBixS3(x = 0.4, 1) with 3D
      Flower-Like Architectures.
AB  - Flower-like nanostructures of Sb2 - xBixS3(x = 0.4, 1.0) were successfully
      prepared using both antimony diethyldithiocarbamate [Sb(DDTC)3] and bismuth
      diethyldithiocarbamate [Bi(DDTC)3] as precursors under solvothermal conditions at
      180  degrees C. The prepared Sb2 - xBixS3 with flower-like 3D architectures were
      characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM),
      energy dispersive X-ray spectrometry (EDS), high-resolution transmission electron
      microscopy (HRTEM), and selected area electron diffraction (SAED). The flower
      like architectures, with an average diameter of ~4 MUm, were composed of single
      crystalline nanorods with orthorhombic structures. The optical absorption
      properties of the Sb2 - xBixS3 nanostructures were investigated by UV-Visible
      spectroscopy, and the results indicate that the Sb2 - xBixS3 compounds are
      semiconducting with direct band gaps of 1.32 and 1.30 eV for x = 0.4 and 1.0,
      respectively. On the basis of the experimental results, a possible growth
      mechanism for the flower-like Sb2 - xBixS3 nanostructures is suggested.

PMID- 20672059
TI  - Synthesis and Magnetic Characterization of Metal-filled Double-sided Porous
      Silicon Samples.
AB  - A magnetic semiconductor/metal nanocomposite with a nanostructured silicon wafer
      as base material and incorporated metallic nanostructures (Ni, Co, NiCo) is
      fabricated in two electrochemical steps. First, the silicon template is anodized
      in an HF-electrolyte to obtain a porous structure with oriented pores grown
      perpendicular to the surface. This etching procedure is carried out either in
      forming a sample with a single porous layer on one side or in producing a double
      sided specimen with a porous layer on each side. Second, this matrix is used for
      deposition of transition metals as Ni, Co or an alloy of these. The achieved
      hybrid material with incorporated Ni- and Co-nanostructures within one sample is
      investigated magnetically. The obtained results are compared with the ones gained
      from samples containing a single metal. 

PMID- 20672060
TI  - Synthesis of Nanoscale Tips Using Femtosecond Laser Radiation under Ambient
      Condition.
AB  - We report a unique growth of platelet-shaped nanoscale tips of transparent
      dielectric using femtosecond laser radiation at MHz pulse repetition rate with
      nitrogen background gas flow under ambient condition. The tips grew with sharp
      nanoscale apex while their base and lengths are of the order of few hundred
      nanometers. In the absence of nitrogen, the irradiation leads to nanofibrous
      structure formation. The collision between the nitrogen gas atoms and the vapor
      species slows down plume expansion and lead to an increase of nanoparticles size.
      This prevents the fibrous structure formation and provides appropriate condition
      for nanoscale tips growth.

PMID- 20672061
TI  - Carbon nanotubes for supercapacitor.
AB  - As an electrical energy storage device, supercapacitor finds attractive
      applications in consumer electronic products and alternative power source due to
      its higher energy density, fast discharge/charge time, low level of heating,
      safety, long-term operation stability, and no disposable parts. This work reviews
      the recent development of supercapacitor based on carbon nanotubes (CNTs) and
      their composites. The purpose is to give a comprehensive understanding of the
      advantages and disadvantages of carbon nanotubes-related supercapacitor materials
      and to find ways for the improvement in the performance of supercapacitor. We
      first discussed the effects of physical and chemical properties of pure carbon
      nanotubes, including size, purity, defect, shape, functionalization, and
      annealing, on the supercapacitance. The composites, including CNTs/oxide and
      CNTs/polymer, were further discussed to enhance the supercapacitance and keep the
      stability of the supercapacitor by optimally engineering the composition,
      particle size, and coverage.

PMID- 20672062
TI  - Accurate Computation of Electric Field Enhancement Factors for Metallic
      Nanoparticles Using the Discrete Dipole Approximation.
AB  - We model the response of nanoscale Ag prolate spheroids to an external uniform
      static electric field using simulations based on the discrete dipole
      approximation, in which the spheroid is represented as a collection of
      polarizable subunits. We compare the results of simulations that employ subunit
      polarizabilities derived from the Clausius-Mossotti relation with those of
      simulations that employ polarizabilities that include a local environmental
      correction for subunits near the spheroid's surface [Rahmani et al. Opt Lett 27:
      2118 (2002)]. The simulations that employ corrected polarizabilities give
      predictions in very good agreement with exact results obtained by solving
      Laplace's equation. In contrast, simulations that employ uncorrected Clausius
      Mossotti polarizabilities substantially underestimate the extent of the electric
      field "hot spot" near the spheroid's sharp tip, and give predictions for the
      field enhancement factor near the tip that are 30 to 50% too small.

PMID- 20672063
TI  - Functionalized Mesoporous SBA-15 with CeF3: Eu3+ Nanoparticle by Three Different
      Methods: Synthesis, Characterization, and Photoluminescence.
AB  - Luminescence functionalization of the ordered mesoporous SBA-15 silica is
      realized by depositing a CeF3: Eu3+ phosphor layer on its surface (denoted as
      CeF3: Eu3+/SBA-15/IS, CeF3: Eu3+/SBA-15/SI and CeF3: Eu3+/SBA-15/SS) using three
      different methods, which are reaction in situ (I-S), solution impregnation (S-I)
      and solid phase grinding synthesis (S-S), respectively. The structure,
      morphology, porosity, and optical properties of the materials are well
      characterized by X-ray diffraction, Fourier transform infrared spectroscopy,
      transmission electron microscopy, N2 adsorption, and photoluminescence spectra.
      These materials all have high surface area, uniformity in the mesostructure and
      crystallinity. As expected, the pore volume, surface area, and pore size of SBA
      15 decrease in sequence after deposition of the CeF3: Eu3+ nanophosphors.
      Furthermore, the efficient energy transfer in mesoporous material mainly occurs
      between the Ce3+ and the central Eu3+ ion. They show the characteristic emission
      of Ce3+ 5d -> 4f (200-320 nm) and Eu3+5D0 -> 7FJ(J = 1-4, with 5D0 -> 7F1 orange
      emission at 588 nm as the strongest one) transitions, respectively. In addition,
      for comparison, the mesoporous material CeF3: Eu3+/SBA-15/SS exhibits the
      characteristic emission of Eu3+ ion under UV irradiation with higher luminescence
      intensity than the other materials.

PMID- 20672064
TI  - Effect of Size-Dependent Thermal Instability on Synthesis of Zn2 SiO4-SiOx Core
      Shell Nanotube Arrays and Their Cathodoluminescence Properties.
AB  - Vertically aligned Zn2SiO4-SiOx(x < 2) core-shell nanotube arrays consisting of
      Zn2SiO4-nanoparticle chains encapsulated into SiOx nanotubes and SiOx-coated
      Zn2SiO4 coaxial nanotubes were synthesized via one-step thermal annealing process
      using ZnO nanowire (ZNW) arrays as templates. The appearance of different
      nanotube morphologies was due to size-dependent thermal instability and specific
      melting of ZNWs. With an increase in ZNW diameter, the formation mechanism
      changed from decomposition of "etching" to Rayleigh instability and then to
      Kirkendall effect, consequently resulting in polycrystalline Zn2SiO4-SiOx coaxial
      nanotubes, single-crystalline Zn2SiO4-nanoparticle-chain-embedded SiOx nanotubes,
      and single-crystalline Zn2SiO4-SiOx coaxial nanotubes. The difference in
      spatially resolved optical properties related to a particular morphology was
      efficiently documented by means of cathodoluminescence (CL) spectroscopy using a
      middle-ultraviolet emission at 310 nm from the Zn2SiO4 phase.

PMID- 20672065
TI  - Platinum-vanadium oxide nanotube hybrids.
AB  - The present contribution reports on the features of platinum-based systems
      supported on vanadium oxide nanotubes. The synthesis of nanotubes was carried out
      using a commercial vanadium pentoxide via hydrothermal route. The nanostructured
      hybrid materials were prepared by wet impregnation using two different platinum
      precursors. The formation of platinum nanoparticles was evaluated by applying
      distinct reduction procedures. All nanostructured samples were essentially
      analysed by X-ray diffraction and transmission electron microscopy. After
      reduction, transmission electron microscopy also made it possible to estimate
      particle size distribution and mean diameter calculations. It could be seen that
      all reduction procedures did not affect the nanostructure of the supports and
      that the formation of metallic nanoparticles is quite efficient with an
      indistinct distribution along the nanotubes. Nevertheless, the reduction
      procedure determined the diameter, dispersion and shape of the metallic
      particles. It could be concluded that the use of H2PtCl6 is more suitable and
      that the use of hydrogen as reducing agent leads to a nanomaterial with
      unagglomerated round-shaped metallic particles with mean size of 6-7 nm.

PMID- 20672066
TI  - Resonant photonic States in coupled heterostructure photonic crystal waveguides.
AB  - In this paper, we study the photonic resonance states and transmission spectra
      of coupled waveguides made from heterostructure photonic crystals. We consider
      photonic crystal waveguides made from three photonic crystals A, B and C, where
      the waveguide heterostructure is denoted as B/A/C/A/B. Due to the band structure
      engineering, light is confined within crystal A, which thus act as waveguides.
      Here, photonic crystal C is taken as a nonlinear photonic crystal, which has a
      band gap that may be modified by applying a pump laser. We have found that the
      number of bound states within the waveguides depends on the width and well depth
      of photonic crystal A. It has also been found that when both waveguides are far
      away from each other, the energies of bound photons in each of the waveguides are
      degenerate. However, when they are brought close to each other, the degeneracy of
      the bound states is removed due to the coupling between them, which causes these
      states to split into pairs. We have also investigated the effect of the pump
      field on photonic crystal C. We have shown that by applying a pump field, the
      system may be switched between a double waveguide to a single waveguide, which
      effectively turns on or off the coupling between degenerate states. This reveals
      interesting results that can be applied to develop new types of nanophotonic
      devices such as nano-switches and nano-transistors.

PMID- 20672067
TI  - Self-Organized Ni Nanocrystal Embedded in BaTiO3 Epitaxial Film.
AB  - Ni nanocrystals (NCs) were embedded in BaTiO3 epitaxial films using the laser
      molecular beam epitaxy. The processes involving the self-organization of Ni NCs
      and the epitaxial growth of BaTiO3 were discussed. With the in situ monitoring of
      reflection high-energy electron diffraction, the nanocomposite films were
      engineered controllably by the fine alternation of the self-organization of Ni
      NCs and the epitaxial growth of BaTiO3. The transmission electron microscopy and
      the X-ray diffraction characterization confirmed that the composite film consists
      of the Ni NCs layers alternating with the (001)/(100)-oriented epitaxial BaTiO3
      separation layers.

PMID- 20672068
TI  - Polaron Hopping in Nano-scale Poly(dA)-Poly(dT) DNA.
AB  - We investigate the current-voltage relationship and the temperature-dependent
      conductance of nano-scale samples of poly(dA)-poly(dT) DNA molecules. A polaron
      hopping model has been used to calculate the I-V characteristic of nano-scale
      samples of DNA. This model agrees with the data for current versus voltage at
      temperatures greater than 100 K. The quantities G(0), i(0), and T(1d) are
      determined empirically, and the conductivity is estimated for samples of poly(dA)
      poly(dT).

PMID- 20672069
TI  - Nanofabrication with pulsed lasers.
AB  - An overview of pulsed laser-assisted methods for nanofabrication, which are
      currently developed in our Institute (LP3), is presented. The methods compass a
      variety of possibilities for material nanostructuring offered by laser-matter
      interactions and imply either the nanostructuring of the laser-illuminated
      surface itself, as in cases of direct laser ablation or laser plasma-assisted
      treatment of semiconductors to form light-absorbing and light-emitting nano
      architectures, as well as periodic nanoarrays, or laser-assisted production of
      nanoclusters and their controlled growth in gaseous or liquid medium to form
      nanostructured films or colloidal nanoparticles. Nanomaterials synthesized by
      laser-assisted methods have a variety of unique properties, not reproducible by
      any other route, and are of importance for photovoltaics, optoelectronics,
      biological sensing, imaging and therapeutics.

PMID- 20672070
TI  - Electronic Structures of S-Doped Capped C-SWNT from First Principles Study.
AB  - The semiconducting single-walled carbon nanotube (C-SWNT) has been synthesized
      by S-doping, and they have extensive potential application in electronic devices.
      We investigated the electronic structures of S-doped capped (5, 5) C-SWNT with
      different doping position using first principles calculations. It is found that
      the electronic structures influence strongly on the workfunction without and with
      external electric field. It is considered that the extended wave functions at the
      sidewall of the tube favor for the emission properties. With the S-doping into
      the C-SWNT, the HOMO and LUMO charges distribution is mainly more localized at
      the sidewall of the tube and the presence of the unsaturated dangling bond, which
      are believed to enhance workfunction. When external electric field is applied,
      the coupled states with mixture of localized and extended states are presented at
      the cap, which provide the lower workfunction. In addition, the wave functions
      close to the cap have flowed to the cap as coupled states and to the sidewall of
      the tube mainly as extended states, which results in the larger workfunction. It
      is concluded that the S-doped C-SWNT is not incentive to be applied in field
      emitter fabrication. The results are also helpful to understand and interpret the
      application in other electronic devices.

PMID- 20672071
TI  - Synthesis of p-and n-type Gels Doped with Ionic Charge Carriers.
AB  - In this study, we synthesized the new kinds of semiconducting polymeric gels
      having negative (n-type) and positive (p-type) counter ions as charge carriers.
      The polyacrylamide gel was doped with pyranine (8-hydroxypyrene-1,3,6-trisulfonic
      acid, trisodium salt), having SO(3)(-) ions as side groups and Na(+) as counter
      ions, so-called p-type semiconducting gel. The doping process was performed
      during the polymerization where the pyranine binds to the polymer strands over OH
      group chemically via radical addition. In a similar way, N-isopropylacrylamide
      (NIPA) gel was doped with methacrylamidopropyltrimethyl ammonium chloride
      (MAPTAC), having Cl(-) as counter ions, so-called n-type semiconducting gel. Here
      MAPTAC was embedded by copolymerization within the polymer network (NIPA). These
      semiconducting gels can show different electrical properties by changing the
      concentration of the doping agents, swelling ratio etc. We have shown that the pn
      junction, formed by combining p-type and n-type gels together in close contact,
      rectifies the current similar to the conventional Si and Ge diodes.

PMID- 20672072
TI  - Synthesis and Electrochemical Sensing Toward Heavy Metals of Bunch-like Bismuth
      Nanostructures.
AB  - Large-scale bunch-like bismuth (Bi) nanostructures were the first time to be
      synthesized via two-step electrochemical deposition. The growth mechanism of the
      nanostructures was discussed. Such a designed bunch-like Bi electrode has high
      sensitivity to detect the heavy metal ions due to its unique three-dimensional
      structures and strong ability of adsorbing the heavy metal ions. The bunch-like
      Bi electrode's detection of heavy metals was statically performed using anodic
      stripping voltammetry (ASV). The detection in the Pb(II) concentration range of
      2.5-50 mug/l was also performed. Based on the experimental results, this bunch
      like Bi electrode can be considered as an interesting alternative to common
      mercury electrodes and bismuth film electrodes for possible use in
      electrochemical studies and electroanalytical applications. 

PMID- 20672073
TI  - Selective deposition and alignment of single-walled carbon nanotubes assisted by
      dielectrophoresis: from thin films to individual nanotubes.
AB  - Dielectrophoresis has been used in the controlled deposition of single-walled
      carbon nanotubes (SWNTs) with the focus on the alignment of nanotube thin films
      and their applications in the last decade. In this paper, we extend the research
      from the selective deposition of SWNT thin films to the alignment of small
      nanotube bundles and individual nanotubes. Electrodes with "teeth"-like patterns
      are fabricated to study the influence of the electrode width on the deposition
      and alignment of SWNTs. The entire fabrication process is compatible with optical
      lithography-based techniques. Therefore, the fabrication cost is low, and the
      resulting devices are inexpensive. A series of SWNT solutions is prepared with
      concentrations ranging from 0.0125 to 0.2 mg/ml. The alignment of SWNT thin
      films, small bundles, and individual nanotubes is achieved under the optimized
      experimental conditions. The electrical properties of these samples are
      characterized; the linear current-voltage plots prove that the aligned SWNTs are
      mainly metallic nanotubes. The microscopy inspection of the samples demonstrates
      that the alignment of small nanotube bundles and individual nanotubes can only be
      achieved using narrow electrodes and low-concentration solutions. Our
      investigation shows that it is possible to deposit a controlled amount of SWNTs
      in desirable locations using dielectrophoresis.

PMID- 20672074
TI  - Cavity Enhancement of Single Quantum Dot Emission in the Blue.
AB  - Cavity-enhanced single-photon emission in the blue spectral region was measured
      from single InGaN/GaN quantum dots. The low-Q microcavities used were
      characterized using micro-reflectance spectroscopy where the source was the
      enhanced blue output from a photonic crystal fibre. Micro-photoluminescence was
      observed from several cavities and found to be ~10 times stronger than typical
      InGaN quantum dot emission without a cavity. The measurements were performed
      using non-linear excitation spectroscopy in order to suppress the background
      emission from the underlying wetting layer.

PMID- 20672075
TI  - Toward Automatic Label-Free Whispering Gallery Modes Biodetection with a Quantum
      Dot-Coated Microsphere Population.
AB  - We explore a new calibration-free approach to biodetection based on whispering
      gallery modes (WGMs) without a reference measure and relative shifts. Thus, the
      requirement to keep track of the sensor position is removed, and a freely moving
      population of fluorophore-doped polystyrene microspheres can now fulfill this
      role of sensing resonator. Breaking free from fixed surface-based biosensing
      promotes adhesion between the microsphere sensors and the analytes since both can
      now be thoroughly mixed. The 70-nm-wide spectrum of green fluorescent microbeads
      allows us to monitor over 20 WGMs simultaneously without needing evanescent light
      coupling into the microspheres, hence enabling remote sensing. Since the exact
      radius of each microsphere is unknown a priori, it requires algorithmic analyses
      to obtain a reliable result for the refractive index of a solution. We first test
      our approach with different solutions of alcohol in water obtaining 3 x 10(-4)
      precision on the refractive index at lower concentrations. Then, the solutions of
      bacterial spores in water yield clear evidence of biodetection in the statistical
      analysis of WGMs from 50 microspheres. To extend the fluorescence spectral range
      of our WGM sensors, we present preliminary results on coating microspheres with
      CdSe/ZnS quantum dots.

PMID- 20672076
TI  - Synthesis and Sensing Properties of ZnO/ZnS Nanocages.
AB  - Large-scale uniform ZnO dumbbells and ZnO/ZnS hollow nanocages were successfully
      synthesized via a facile hydrothermal route combined with subsequent etching
      treatment. The nanocages were formed through preferential dissolution of the
      twinned (0001) plane of ZnO dumbbells. Due to their special morphology, the
      hollow nanocages show better sensing properties to ethanol than ZnO dumbbells.
      The gain in sensitivity is attributed to both the interface between ZnO and ZnS
      heterostructure and their hollow architecture that promotes analyte diffusion and
      increases the available active surface area.

PMID- 20672077
TI  - Effects of Crystalline Anisotropy and Indenter Size on Nanoindentation by
      Multiscale Simulation.
AB  - Nanoindentation processes in single crystal Ag thin film under different
      crystallographic orientations and various indenter widths are simulated by the
      quasicontinuum method. The nanoindentation deformation processes under influences
      of crystalline anisotropy and indenter size are investigated about hardness, load
      distribution, critical load for first dislocation emission and strain energy
      under the indenter. The simulation results are compared with previous
      experimental results and Rice-Thomson (R-T) dislocation model solution. It is
      shown that entirely different dislocation activities are presented under the
      effect of crystalline anisotropy during nanoindentation. The sharp load drops in
      the load-displacement curves are caused by the different dislocation activities.
      Both crystalline anisotropy and indenter size are found to have distinct effect
      on hardness, contact stress distribution, critical load for first dislocation
      emission and strain energy under the indenter. The above quantities are decreased
      at the indenter into Ag thin film along the crystal orientation with more
      favorable slip directions that easy trigger slip systems; whereas those will
      increase at the indenter into Ag thin film along the crystal orientation with
      less or without favorable slip directions that hard trigger slip systems. The
      results are shown to be in good agreement with experimental results and R-T
      dislocation model solution. 

PMID- 20672078
TI  - A nonaqueous approach to the preparation of iron phosphide nanowires.
AB  - Previous preparation of iron phosphide nanowires usually employed toxic and
      unstable iron carbonyl compounds as precursor. In this study, we demonstrate that
      iron phosphide nanowires can be synthesized via a facile nonaqueous chemical
      route that utilizes a commonly available iron precursor, iron (III)
      acetylacetonate. In the synthesis, trioctylphosphine (TOP) and trioctylphosphine
      oxide (TOPO) have been used as surfactants, and oleylamine has been used as
      solvent. The crystalline structure and morphology of the as-synthesized products
      were characterized by powder X-ray diffraction (XRD) and transmission electron
      microscopy (TEM). The obtained iron phosphide nanowires have a typical width of
      ~16 nm and a length of several hundred nanometers. Structural and compositional
      characterization reveals a hexagonal Fe2P crystalline phase. The morphology of as
      synthesized products is greatly influenced by the ratio of TOP/TOPO. The presence
      of TOPO has been found to be essential for the growth of high-quality iron
      phosphide nanowires. Magnetic measurements reveal ferromagnetic characteristics,
      and hysteresis behaviors below the blocking temperature have been observed.

PMID- 20672079
TI  - Nanodiamonds as Carriers for Address Delivery of Biologically Active Substances.
AB  - Surface of detonation nanodiamonds was functionalized for the covalent attachment
      of immunoglobulin, and simultaneously bovine serum albumin and Rabbit Anti-Mouse
      Antibody. The nanodiamond-IgG(I125) and RAM-nanodiamond-BSA(I125) complexes are
      stable in blood serum and the immobilized proteins retain their biological
      activity. It was shown that the RAM-nanodiamond-BSA(I125) complex is able to bind
      to the target antigen immobilized on the Sepharose 6B matrix through antibody
      antigen interaction. The idea can be extended to use nanodiamonds as carriers for
      delivery of bioactive substances (i.e., drugs) to various targets in vivo.

PMID- 20672080
TI  - New Bending Algorithm for Field-Driven Molecular Dynamics.
AB  - A field-driven bending method is introduced in this paper according to the
      coordinate transformation between straight and curved coordinates. This novel
      method can incorporate with the periodic boundary conditions in analysis along
      axial, bending, and transverse directions. For the case of small bending, the
      bending strain can be compatible with the beam theory. Consequently, it can be
      regarded as a generalized SLLOD algorithm. In this work, the bulk copper beam
      under bending is analyzed first by the novel bending method. The bending stress
      estimated here is well consistent to the results predicted by the beam theory.
      Moreover, a hollow nanowire is also analyzed. The zigzag traces of atomic stress
      and the corresponding 422 common neighbor type can be observed near the inner
      surface of the hollow nanowire, which values are increased with an increase of
      time. It can be seen that the novel bending method with periodic boundary
      condition along axial direction can provide a more physical significance than the
      traditional method with fixed boundary condition. 

PMID- 20672081
TI  - Effect of Nitric Acid "Washing" Procedure on Electrochemical Behavior of Carbon
      Nanotubes and Glassy Carbon MU-Particles.
AB  - The electroanalytic performances of glassy carbon paste electrode (GCPE), multi
      walled carbon nanotube (MWCNT)-GCPE and double-walled carbon nanotube (DWCNT)
      GCPE, which include HNO3 washed/unwashed materials, were compared by monitoring
      cyclic voltammograms of potassium ferricyanide and catechol. Electrodes were
      prepared by introducing proper amount of DWCNT and MWCNT into GCPE. First
      untreated materials (DWCNT, MWCNT, GC MU-particles) were used in the electrodes
      and then HNO3-treated materials were utilized for comparing difference in
      electrochemical performances. The effect of treatment procedure was also examined
      by applying Raman spectroscopy to treated and untreated materials. Moreover, TEM
      images were obtained for further investigation of MWCNT and DWCNT.

PMID- 20672082
TI  - Electrodeposition and capacitive behavior of films for electrodes of
      electrochemical supercapacitors.
AB  - Polypyrrole films were deposited by anodic electropolymerization on stainless
      steel substrates from aqueous pyrrole solutions containing sodium salicylate and
      tiron additives. The deposition yield was studied under galvanostatic conditions.
      The amount of the deposited material was varied by the variation of deposition
      time at a constant current density. SEM studies showed the formation of porous
      films with thicknesses in the range of 0-3 MUm. Cyclic voltammetry data for the
      films tested in 0.5 M Na2SO4 solutions showed capacitive behavior and high
      specific capacitance (SC) in a voltage window of 0.9 V. The films prepared from
      pyrrole solutions containing tiron showed better capacitive behavior compared to
      the films prepared from the solutions containing sodium salicylate. A highest SC
      of 254 F g-1 was observed for the sample with a specific mass of 89 MUg cm-2 at a
      scan rate of 2 mV s-1. The SC decreased with an increasing film thickness and
      scan rate. The results indicated that the polypyrrole films deposited on the
      stainless steel substrates by anodic electropolymerization can be used as
      electrodes for electrochemical supercapacitors (ES).

PMID- 20672083
TI  - Coupling of semiconductor nanowires with neurons and their interfacial structure.
AB  - We report on the compatibility of various nanowires with hippocampal neurons and
      the structural study of the neuron-nanowire interface. Si, Ge, SiGe, and GaN
      nanowires are compatible with hippocampal neurons due to their native oxide, but
      ZnO nanowires are toxic to neuron due to a release of Zn ion. The interfaces of
      fixed Si nanowire and hippocampal neuron, cross-sectional samples, were prepared
      by focused ion beam and observed by transmission electron microscopy. The results
      showed that the processes of neuron were adhered well on the nanowire without
      cleft.

PMID- 20672084
TI  - The Study of Quantum Interference in Metallic Photonic Crystals Doped with Four
      Level Quantum Dots.
AB  - In this work, the absorption coefficient of a metallic photonic crystal doped
      with nanoparticles has been obtained using numerical simulation techniques. The
      effects of quantum interference and the concentration of doped particles on the
      absorption coefficient of the system have been investigated. The nanoparticles
      have been considered as semiconductor quantum dots which behave as a four-level
      quantum system and are driven by a single coherent laser field. The results show
      that changing the position of the photonic band gap about the resonant energy of
      the two lower levels directly affects the decay rate, and the system can be
      switched between transparent and opaque states if the probe laser field is tuned
      to the resonance frequency. These results provide an application for metallic
      nanostructures in the fabrication of new optical switches and photonic devices.

PMID- 20672085
TI  - ZnSe/ZnSeTe Superlattice Nanotips.
AB  - The authors report the growth of ZnSe/ZnSeTe superlattice nanotips on oxidized
      Si(100) substrate. It was found the nanotips exhibit mixture of cubic zinc-blende
      and hexagonal wurtzite structures. It was also found that photoluminescence
      intensities observed from the ZnSe/ZnSeTe superlattice nanotips were much larger
      than that observed from the homogeneous ZnSeTe nanotips. Furthermore, it was
      found that activation energies for the ZnSe/ZnSeTe superlattice nanotips with
      well widths of 16, 20, and 24 nm were 76, 46, and 19 meV, respectively.

PMID- 20672086
TI  - Hematological parameters and the state of liver cells of rats after oral
      administration of aflatoxin b1 alone and together with nanodiamonds.
AB  - Hematological parameters and the state of liver cells of rats were examined in
      vivo after the animals received aflatoxin B1 (AfB1) alone and together with
      modified nanodiamonds (MND) synthesized by detonation. The rats that had received
      the MND hydrosol had elevated leukocyte levels, mainly due to higher granulocyte
      counts and somewhat increased monocyte counts compared to control rats.
      Hematological parameters of the rats that had received AfB1 alone differed from
      those of the control rats in another way: total white blood cell counts were
      significantly lower due to the decreased lymphocyte counts. In rats that had
      consumed AfB1 with the MND hydrosol, changes in hematological parameters were
      less pronounced than in rats that had consumed either AfB1 or MND. Electron
      microscopy showed that hepatocytes of the rats that had received the MND hydrosol
      or AfB1 with the MND hydrosol contained elevated levels of lipid inclusions and
      lysosomes. Hyperplasia of the smooth endoplasmic reticulum (EPR) was revealed in
      liver specimens of the rats that had received AfB1. Results of the study suggest
      the conclusion about mutual mitigation of the effects of nanoparticles and the
      mycotoxin on rats blood and liver cells after AfB1 has adsorbed on MND.

PMID- 20672087
TI  - Study on Composition Distribution and Ferromagnetism of Monodisperse FePt
      Nanoparticles.
AB  - Monodisperse FePt nanoparticles with size of 4.5 and 6.0 nm were prepared by
      simultaneous reduction of platinum acetylacetonate and thermal decomposition of
      iron pentacarbonyl in benzylether. The crystallography structure, size, and
      composition of the FePt nanoparticles were examined by X-ray diffraction and
      transmission electron microscopy. Energy dispersive X-ray spectrometry
      measurements of individual particles indicate a broad compositional distribution
      in both the 4.5 and 6 nm FePt nanoparticles. The effects of compositional
      distribution on the phase-transition and magnetic properties of the FePt
      nanoparticles were investigated.

PMID- 20672088
TI  - Theoretical investigations into self-organized ordered metallic semi-clusters
      arrays on metallic substrate.
AB  - Using the energy minimization calculations based on an interfacial potential and
      a first-principles total energy method, respectively, we show that (2 * 2)/(3 *
      3) Pb/Cu(111) system is a stable structure among all the [(n - 1) * (n - 1)]/(n *
      n) Pb/Cu(111) (n = 2, 3,..., 12) structures. The electronic structure
      calculations indicate that self-organized ordered Pb semi-clusters arrays are
      formed on the first Pb monolayer of (2 * 2)/(3 * 3) Pb/Cu(111), which is due to a
      strain-release effect induced by the inherent misfits. The Pb semi-clusters
      structure can generate selective adsorption of atoms of semiconductor materials
      (e.g., Ge) around the semi-clusters, therefore, can be used as a template for the
      growth of nanoscale structures with a very short periodic length (7.67 A).

PMID- 20672089
TI  - Influence of Ni Catalyst Layer and TiN Diffusion Barrier on Carbon Nanotube
      Growth Rate.
AB  - Dense, vertically aligned multiwall carbon nanotubes were synthesized on TiN
      electrode layers for infrared sensing applications. Microwave plasma-enhanced
      chemical vapor deposition and Ni catalyst were used for the nanotubes synthesis.
      The resultant nanotubes were characterized by SEM, AFM, and TEM. Since the length
      of the nanotubes influences sensor characteristics, we study in details the
      effects of changing Ni and TiN thickness on the physical properties of the
      nanotubes. In this paper, we report the observation of a threshold Ni thickness
      of about 4 nm, when the average CNT growth rate switches from an increasing to a
      decreasing function of increasing Ni thickness, for a process temperature of 700
      degrees C. This behavior is likely related to a transition in the growth mode
      from a predominantly "base growth" to that of a "tip growth." For Ni layer
      greater than 9 nm the growth rate, as well as the CNT diameter, variations become
      insignificant. We have also observed that a TiN barrier layer appears to favor
      the growth of thinner CNTs compared to a SiO(2) layer.

PMID- 20672090
TI  - InGaAs Quantum Well Grown on High-Index Surfaces for Superluminescent Diode
      Applications.
AB  - The morphological and optical properties of In0.2Ga0.8As/GaAs quantum wells
      grown on various substrates are investigated for possible application to
      superluminescent diodes. The In0.2Ga0.8As/GaAs quantum wells are grown by
      molecular beam epitaxy on GaAs (100), (210), (311), and (731) substrates. A broad
      photoluminescence emission peak (~950 nm) with a full width at half maximum
      (FWHM) of 48 nm is obtained from the sample grown on (210) substrate at room
      temperature, which is over four times wider than the quantum well simultaneously
      grown on (100) substrate. On the other hand, a very narrow photoluminescence
      spectrum is observed from the sample grown on (311) with FWHM = 7.8 nm. The
      results presented in this article demonstrate the potential of high-index GaAs
      substrates for superluminescent diode applications.

PMID- 20672091
TI  - Nanostructured Silver Substrates With Stable and Universal SERS Properties:
      Application to Organic Molecules and Semiconductor Nanoparticles.
AB  - Nanostructured silver films have been prepared by thermal deposition on silicon,
      and their properties as SERS substrates investigated. The optimal conditions of
      the post-growth annealing of the substrates were established. Atomic force
      microscopy study revealed that the silver films with relatively dense and
      homogeneous arrays of 60-80-nm high pyramidal nanoislands are the most efficient
      for SERS of both organic dye and inorganic nanoparticles analytes. The noticeable
      enhancement of the Raman signal from colloidal nanoparticles with the help of
      silver island films is reported for the first time. 

PMID- 20672092
TI  - Modeling Electrolytically Top-Gated Graphene.
AB  - We investigate doping of a single-layer graphene in the presence of electrolytic
      top gating. The interfacial phenomenon is modeled using a modified Poisson
      Boltzmann equation for an aqueous solution of simple salt. We demonstrate both
      the sensitivity of graphene's doping levels to the salt concentration and the
      importance of quantum capacitance that arises due to the smallness of the Debye
      screening length in the electrolyte.

PMID- 20672093
TI  - Biomolecules Detection Using a Silver-Enhanced Gold Nanoparticle-Based Biochip.
AB  - Silver-enhanced labeling method has been employed in immunochromatographic assays
      for improving the sensitivity of detecting pathogens. In this paper, we apply the
      silver enhancement technique for biomolecular signal amplification in a gold
      nanoparticle-based conductimetric biochip. We show that the response of the
      silver-enhanced biochip comprises two distinct regions namely: (a) a sub
      threshold region where conduction occurs due to electron hopping between silver
      islands and the electrolyte and (b) an above-threshold region where the
      conduction is due to a direct flow of electrons. These two regions are
      characterized by different conduction slopes, and we show that combining the
      information from both these regions can improve the sensitivity of the biochip.
      Results from fabricated prototypes show a dynamic range of more than 40 dB and
      with a detection limit less than 240 pg/mL. The fabrication of the biochip is
      compatible with standard complementary metal-oxide-semiconductor (CMOS) processes
      making it ideal for integration in next-generation CMOS biosensors.

PMID- 20672094
TI  - Carbon-Coated SnO(2) Nanorod Array for Lithium-Ion Battery Anode Material.
AB  - Carbon-coated SnO(2) nanorod array directly grown on the substrate has been
      prepared by a two-step hydrothermal method for anode material of lithium-ion
      batteries (LIBs). The structural, morphological and electrochemical properties
      were investigated by means of X-ray diffraction (XRD), scanning electron
      microscopy (SEM), transmission electron microscopy (TEM) and electrochemical
      measurement. When used as anodes for LIBs with high current density, as-obtained
      array reveals excellent cycling stability and rate capability. This
      straightforward approach can be extended to the synthesis of other carbon-coated
      metal oxides for application of LIBs.

PMID- 20672095
TI  - Nanoscale Science and Technology for Electronics, Photonics and Renewable Energy
      Applications: Selected Papers from NGC2009 & CSTC2009 conference
      (http://asdn.net/ngc2009/).

PMID- 20672096
TI  - Berkovich Nanoindentation on AlN Thin Films.
AB  - Berkovich nanoindentation-induced mechanical deformation mechanisms of AlN thin
      films have been investigated by using atomic force microscopy (AFM) and cross
      sectional transmission electron microscopy (XTEM) techniques. AlN thin films are
      deposited on the metal-organic chemical-vapor deposition (MOCVD) derived Si-doped
      (2 * 1017 cm-3) GaN template by using the helicon sputtering system. The XTEM
      samples were prepared by means of focused ion beam (FIB) milling to accurately
      position the cross-section of the nanoindented area. The hardness and Young's
      modulus of AlN thin films were measured by a Berkovich nanoindenter operated with
      the continuous contact stiffness measurements (CSM) option. The obtained values
      of the hardness and Young's modulus are 22 and 332 GPa, respectively. The XTEM
      images taken in the vicinity regions just underneath the indenter tip revealed
      that the multiple "pop-ins" observed in the load-displacement curve during
      loading are due primarily to the activities of dislocation nucleation and
      propagation. The absence of discontinuities in the unloading segments of load
      displacement curve suggests that no pressure-induced phase transition was
      involved. Results obtained in this study may also have technological implications
      for estimating possible mechanical damages induced by the fabrication processes
      of making the AlN-based devices.

PMID- 20672097
TI  - Influence of Cobalt Doping on the Physical Properties of Zn0.9Cd0.1S
      Nanoparticles.
AB  - Zn0.9Cd0.1S nanoparticles doped with 0.005-0.24 M cobalt have been prepared by
      co-precipitation technique in ice bath at 280 K. For the cobalt concentration
      >0.18 M, XRD pattern shows unidentified phases along with Zn0.9Cd0.1S sphalerite
      phase. For low cobalt concentration (<=0.05 M) particle size, dXRDis ~3.5 nm,
      while for high cobalt concentration (>0.05 M) particle size decreases abruptly
      (~2 nm) as detected by XRD. However, TEM analysis shows the similar particle size
      (~3.5 nm) irrespective of the cobalt concentration. Local strain in the alloyed
      nanoparticles with cobalt concentration of 0.18 M increases ~46% in comparison to
      that of 0.05 M. Direct to indirect energy band-gap transition is obtained when
      cobalt concentration goes beyond 0.05 M. A red shift in energy band gap is also
      observed for both the cases. Nanoparticles with low cobalt concentrations were
      found to have paramagnetic nature with no antiferromagnetic coupling. A negative
      Curie-Weiss temperature of -75 K with antiferromagnetic coupling was obtained for
      the high cobalt concentration.

PMID- 20672098
TI  - Tunable magnetic properties of heterogeneous nanobrush: from nanowire to
      nanofilm.
AB  - With a bottom-up assemble technology, heterogeneous magnetic nanobrushes,
      consisting of Co nanowire arrays and ferromagnetic Fe70Co30 nanofilm, have been
      fabricated using an anodic aluminum oxide template method combining with
      sputtering technology. Magnetic measurement suggests that the magnetic anisotropy
      of nanobrush depends on the thickness of Fe70Co30 layer, and its total anisotropy
      originates from the competition between the shape anisotropy of nanowire arrays
      and nanofilm. Micromagnetic simulation result indicates that the switching field
      of nanobrush is 1900 Oe, while that of nanowire array is 2700 Oe. These suggest
      that the nanobrush film can promote the magnetization reversal processes of
      nanowire arrays in nanobrush.

PMID- 20672099
TI  - Crystal growth of thiol-stabilized gold nanoparticles by heat-induced
      coalescence.
AB  - A monolayer of dodecanethiol-stabilized gold nanoparticles changed into two
      dimensional and three-dimensional self-organized structures by annealing at 323
      K. Subsequent crystal growth of gold nanoparticles occurred. Thiol molecules,
      although chemisorbed, form relatively unstable bonds with the gold surface; a few
      thiols desorbed from the surface and oxidized to disulfides at 323 K, because the
      interaction energy between thiol macromolecules is larger than that between a
      thiol and a nanoparticle. The gold nanoparticles approached each other and grew
      into large single or twinned crystals because of the van der Waals attraction and
      the heat generated by the exothermic formation of disulfides.

PMID- 20672101
TI  - Composite electrodes for electrochemical supercapacitors.
AB  - Manganese dioxide nanofibers with length ranged from 0.1 to 1 MUm and a diameter
      of about 4-6 nm were prepared by a chemical precipitation method. Composite
      electrodes for electrochemical supercapacitors were fabricated by impregnation of
      the manganese dioxide nanofibers and multiwalled carbon nanotubes (MWCNT) into
      porous Ni plaque current collectors. Obtained composite electrodes, containing
      85% of manganese dioxide and 15 mass% of MWCNT, as a conductive additive, with
      total mass loading of 7-15 mg cm-2, showed a capacitive behavior in 0.5-M Na2SO4
      solutions. The decrease in stirring time during precipitation of the nanofibers
      resulted in reduced agglomeration and higher specific capacitance (SC). The
      highest SC of 185 F g-1 was obtained at a scan rate of 2 mV s-1 for mass loading
      of 7 mg cm-2. The SC decreased with increasing scan rate and increasing electrode
      mass.

PMID- 20672100
TI  - Natriuretic Peptides and Assessment of Cardiovascular Disease Risk in
      Asymptomatic Persons.
AB  - Current tools for cardiovascular disease (CVD) risk assessment in asymptomatic
      individuals are imperfect. Preventive measures aimed only at individuals deemed
      high risk by current algorithms neglect large numbers of low-risk and
      intermediate-risk individuals who are destined to develop CVD and who would
      benefit from early and aggressive treatment. Natriuretic peptides have the
      potential both to identify individuals at risk for future cardiovascular events
      and to help detect subclinical CVD. Choosing the appropriate subpopulation to
      target for natriuretic peptide testing will help maximize the performance and the
      cost effectiveness. The combined use of multiple risk markers, including
      biomarkers, genetic testing, and imaging or other noninvasive measures of risk,
      offers promise for further refining risk assessment algorithms. Recent studies
      have highlighted the utility of natriuretic peptides for preoperative risk
      stratification; however, cost effectiveness and outcomes studies are needed to
      affirm this and other uses of natriuretic peptides for cardiovascular risk
      assessment in asymptomatic individuals.

PMID- 20672102
TI  - Luminescent Organic-Inorganic Hybrids of Functionalized Mesoporous Silica SBA-15
      by Thio-Salicylidene Schiff Base.
AB  - Novel organic-inorganic mesoporous luminescent hybrid material N, N'
      bis(salicylidene)-thiocarbohydrazide (BSTC-SBA-15) has been obtained by co
      condensation of tetraethyl orthosilicate and the organosilane in the presence of
      Pluronic P123 surfactant as a template. N,N'-bis(salicylidene)-thiocarbohydrazide
      (BSTC) grafted to the coupling agent 3-(triethoxysilyl)-propyl isocyanate
      (TESPIC) was used as the precursor for the preparation of mesoporous materials.
      In addition, for comparison, SBA-15 doped with organic ligand BSTC was also
      synthesized, denoted as BSTC/SBA-15. This organic-inorganic hybrid material was
      well-characterized by X-ray diffraction, Fourier transform infrared spectroscopy,
      transmission electron microscopy (HRTEM), and photoluminescence spectra, which
      reveals that they all have high surface area, uniformity in the mesostructure.
      The resulting materials (BSTC-SBA-15 and BSTC/SBA-15) exhibit regular uniform
      microstructures, and no phase separation happened for the organic and the
      inorganic compounds was covalently linked through Si-O bonds via a self-assemble
      process. Furthermore, the two materials have different luminescence range:
      BSTC/SBA-15 presents the strong dominant green luminescence, while BSTC
      functionalized material BSTC-SBA-15 shows the dominant blue emission.

PMID- 20672103
TI  - Morphological and electrochemical properties of crystalline praseodymium oxide
      nanorods.
AB  - Highly crystalline Pr6O11 nanorods were prepared by a simple precipitation
      method of triethylamine complex at 500 degrees C. Synthesized Pr6O11 nanorods
      were uniformly grown with the diameter of 12-15 nm and the length of 100-150 nm
      without any impurities of unstable PrO2 phase. The Pr6O11 nanorod electrodes
      attained a high electrical conductivity of 0.954 Scm-1 with low activation energy
      of 0.594 eV at 850 degrees C. The electrochemical impedance study showed that the
      resistance of electrode was significantly decreased at high temperature, which
      resulted from its high conductivity and low activation energy. The reduced
      impedance and high electrical conductivity of Pr6O11 nanorod electrodes are
      attributed to the reduction of grain boundaries and high space charge width.

PMID- 20672104
TI  - AFM, SEM and TEM Studies on Porous Anodic Alumina.
AB  - Porous anodic alumina (PAA) has been intensively studied in past decade due to
      its applications for fabricating nanostructured materials. Since PAA's pore
      diameter, thickness and shape vary too much, a systematical study on the methods
      of morphology characterization is meaningful and essential for its proper
      development and utilization. In this paper, we present detailed AFM, SEM and TEM
      studies on PAA and its evolvements with abundant microstructures, and discuss the
      advantages and disadvantages of each method. The sample preparation, testing
      skills and morphology analysis are discussed, especially on the differentiation
      during characterizing complex cross-sections and ultrasmall nanopores. The
      versatility of PAAs is also demonstrated by the diversity of PAAs'
      microstructure.

PMID- 20672105
TI  - Temperature dependence of photoelectrical properties of single selenium
      nanowires.
AB  - Influence of temperature on photoconductivity of single Se nanowires has been
      studied. Time response of photocurrent at both room temperature and low
      temperature suggests that the trap states play an important role in the
      photoelectrical process. Further investigations about light intensity dependence
      on photocurrent at different temperatures reveal that the trap states
      significantly affect the carrier generation and recombination. This work may be
      valuable for improving the device optoelectronic performances by understanding
      the photoelectrical properties.

PMID- 20672106
TI  - Profile prediction and fabrication of wet-etched gold nanostructures for
      localized surface plasmon resonance.
AB  - Dispersed nanosphere lithography can be employed to fabricate gold
      nanostructures for localized surface plasmon resonance, in which the gold film
      evaporated on the nanospheres is anisotropically dry etched to obtain gold
      nanostructures. This paper reports that by wet etching of the gold film, various
      kinds of gold nanostructures can be fabricated in a cost-effective way. The shape
      of the nanostructures is predicted by profile simulation, and the localized
      surface plasmon resonance spectrum is observed to be shifting its extinction peak
      with the etching time.(See supplementary material 1).

PMID- 20672107
TI  - Thermal properties of carbon nanotube-copper composites for thermal management
      applications.
AB  - Carbon nanotube-copper (CNT/Cu) composites have been successfully synthesized by
      means of a novel particles-compositing process followed by spark plasma sintering
      (SPS) technique. The thermal conductivity of the composites was measured by a
      laser flash technique and theoretical analyzed using an effective medium
      approach. The experimental results showed that the thermal conductivity unusually
      decreased after the incorporation of CNTs. Theoretical analyses revealed that the
      interfacial thermal resistance between the CNTs and the Cu matrix plays a crucial
      role in determining the thermal conductivity of bulk composites, and only small
      interfacial thermal resistance can induce a significant degradation in thermal
      conductivity for CNT/Cu composites. The influence of sintering condition on the
      thermal conductivity depended on the combined effects of multiple factors, i.e.
      porosity, CNTs distribution and CNT kinks or twists. The composites sintered at
      600 degrees C for 5 min under 50 MPa showed the maximum thermal conductivity.
      CNT/Cu composites are considered to be a promising material for thermal
      management applications.

PMID- 20672108
TI  - Template-assisted synthesis and characterization of passivated nickel
      nanoparticles.
AB  - Potential applications of nickel nanoparticles demand the synthesis of self
      protected nickel nanoparticles by different synthesis techniques. A novel and
      simple technique for the synthesis of self-protected nickel nanoparticles is
      realized by the inter-matrix synthesis of nickel nanoparticles by cation exchange
      reduction in two types of resins. Two different polymer templates namely strongly
      acidic cation exchange resins and weakly acidic cation exchange resins provided
      with cation exchange sites which can anchor metal cations by the ion exchange
      process are used. The nickel ions which are held at the cation exchange sites by
      ion fixation can be subsequently reduced to metal nanoparticles by using sodium
      borohydride as the reducing agent. The composites are cycled repeating the
      loading reduction cycle involved in the synthesis procedure. X-Ray Diffraction,
      Scanning Electron Microscopy, Transmission Electron microscopy, Energy Dispersive
      Spectrum, and Inductively Coupled Plasma Analysis are effectively utilized to
      investigate the different structural characteristics of the nanocomposites. The
      hysteresis loop parameters namely saturation magnetization and coercivity are
      measured using Vibrating Sample Magnetometer. The thermomagnetization study is
      also conducted to evaluate the Curie temperature values of the composites. The
      effect of cycling on the structural and magnetic characteristics of the two
      composites are dealt in detail. A comparison between the different
      characteristics of the two nanocomposites is also provided.

PMID- 20672109
TI  - One-pot silver nanoring synthesis.
AB  - Silver colloidal nanorings have been synthesized by reducing silver ions with
      NaBH4 in trisodium citrate buffers. pH increase, by addition of NaOH, was used to
      speed up reduction reaction. The UV-vis absorption spectra of resulting silver
      nanorings showed two peaks accounting for transverse and longitudinal surface
      plasmon resonance, at ~400 nm, and between 600 and 700 nm, respectively. The
      shapes of these silver nanoparticles (nanorings) depended on AgNO3/NaBH4 ratio,
      pH and reaction temperature. Particles were analysed by transmission electron
      microscopy, scanning electron microscopy and X-ray diffraction. A reaction
      pathway is proposed to explain silver nanoring formation.

PMID- 20672110
TI  - Steps to Better Cardiovascular Health: How Many Steps Does It Take to Achieve
      Good Health and How Confident Are We in This Number?
AB  - Pedometers and other types of step-counting devices are growing in popularity
      with both researchers and practitioners. The focus of this article is on
      describing the most recent pedometer-related advances in terms of cardiovascular
      health. The emergent body of evidence suggests that pedometer-determined physical
      activity is related to a number of cardiovascular health outcomes and that
      intervention participants can realize modest changes in body mass index and blood
      pressure. Taking into consideration individual baseline values, tailored messages
      congruent with public health recommendations should promote incremental increases
      in steps/day on the order of an extra 3,000 to 4,000 (approximately 30 min) of at
      least moderate intensity and taken in at least 10-minute bouts. Additional health
      benefits accrue with greater increases. Of course, even more benefits are
      possible from engaging in vigorous physical activity, but this seems less
      appealing for most people. Pedometer-based guidelines are not intended to
      supplant existing public health recommendations, but rather supplement them.

PMID- 20672111
TI  - Impacts of coulomb interactions on the magnetic responses of excitonic complexes
      in single semiconductor nanostructures.
AB  - We report on the diamagnetic responses of different exciton complexes in single
      InAs/GaAs self-assembled quantum dots (QDs) and quantum rings (QRs). For QDs, the
      imbalanced magnetic responses of inter-particle Coulomb interactions play a
      crucial role in the diamagnetic shifts of excitons (X), biexcitons (XX), and
      positive trions (X-). For negative trions (X-) in QDs, anomalous magnetic
      responses are observed, which cannot be described by the conventional quadratic
      energy shift with the magnetic field. The anomalous behavior is attributed to the
      apparent change in the electron wave function extent after photon emission due to
      the strong Coulomb attraction by the hole in its initial state. In QRs, the
      diamagnetic responses of X and XX also show different behaviors. Unlike QDs, the
      diamagnetic shift of XX in QRs is considerably larger than that of X. The
      inherent structural asymmetry combined with the inter-particle Coulomb
      interactions makes the wave function distribution of XX very different from that
      of X in QRs. Our results suggest that the phase coherence of XX in QRs may
      survive from the wave function localization due to the structural asymmetry or
      imperfections.

PMID- 20672112
TI  - Study on Growth Kinetics of CdSe Nanocrystals with a New Model.
AB  - A model which involves both bulk diffusion process and surface reaction process
      has been developed for describing the growth behaviour of nanoparticles. When the
      model is employed, hypothesising that either of the processes alone dominates the
      overall growth process is unnecessary. Conversely, the relative magnitude of
      contributions from both processes could be obtained from the model. Using this
      model in our system, the growth process of CdSe QDs demonstrated two different
      growth stages. During the first stage, the growth of CdSe QDs was dominated by
      bulk diffusion, whereas, neither the bulk diffusion process nor the surface
      reaction process could be neglected during the later stage. At last, we
      successfully modelled the Ostwald ripening of CdSe QDs with LSW theories.

PMID- 20672113
TI  - Platinum assisted vapor-liquid-solid growth of er-si nanowires and their optical
      properties.
AB  - We report the optical activation of erbium coated silicon nanowires (Er-SiNWs)
      grown with the assist of platinum (Pt) and gold (Au), respectively. The NWs were
      grown on Si substrates by using a chemical vapor transport process using SiCl4
      and ErCl4 as precursors. Pt as well as Au worked successfully as vapor-liquid
      solid (VLS) catalysts for growing SiNWs with diameters of ~100 nm and length of
      several micrometers, respectively. The SiNWs have core-shell structures where the
      Er-crystalline layer is sandwiched between silica layers. Photoluminescence
      spectra analyses showed the optical activity of SiNWs from both Pt and Au. A
      stronger Er3+ luminescence of 1,534 nm was observed from the SiNWs with Pt at
      room- and low-temperature (25 K) using the 488- and/or 477-nm line of an Ar laser
      that may be due to the uniform incorporation of more Er ions into NWs with the
      exclusion of the formation of catalyst-induced deep levels in the band-gap. Pt
      would be used as a VLS catalyst for high performance optically active Er-SiNWs.

PMID- 20672114
TI  - Nano-regime Length Scales Extracted from the First Sharp Diffraction Peak in Non
      crystalline SiO(2) and Related Materials: Device Applications.
AB  - This paper distinguishes between two different scales of medium range order, MRO,
      in non-crystalline SiO(2): (1) the first is ~0.4 to 0.5 nm and is obtained from
      the position of the first sharp diffraction peak, FSDP, in the X-ray diffraction
      structure factor, S(Q), and (2) the second is ~1 nm and is calculated from the
      FSDP full-width-at-half-maximum FWHM. Many-electron calculations yield Si-O third
      and O-O fourth-nearest-neighbor bonding distances in the same 0.4-0.5 nm MRO
      regime. These derive from the availability of empty Si dpi orbitals for back
      donation from occupied O ppi orbitals yielding narrow symmetry determined
      distributions of third neighbor Si-O, and fourth neighbor O-O distances. These
      are segments of six member rings contributing to connected six-member rings with
      ~1 nm length scale within the MRO regime. The unique properties of non
      crystalline SiO(2) are explained by the encapsulation of six-member ring clusters
      by five- and seven-member rings on average in a compliant hard-soft nano-scaled
      inhomogeneous network. This network structure minimizes macroscopic strain,
      reducing intrinsic bonding defects as well as defect precursors. This
      inhomogeneous CRN is enabling for applications including thermally grown ~1.5 nm
      SiO(2) layers for Si field effect transistor devices to optical components with
      centimeter dimensions. There are qualitatively similar length scales in nano
      crystalline HfO(2) and phase separated Hf silicates based on the primitive unit
      cell, rather than a ring structure. Hf oxide dielectrics have recently been used
      as replacement dielectrics for a new generation of Si and Si/Ge devices heralding
      a transition into nano-scale circuits and systems on a Si chip.

PMID- 20672115
TI  - Nonstoichiometric Titanium Oxides via Pulsed Laser Ablation in Water.
AB  - Titanium oxide compounds TiO,Ti2O3, and TiO2 with a considerable extent of
      nonstoichiometry were fabricated by pulsed laser ablation in water and
      characterized by X-ray/electron diffraction, X-ray photoelectron spectroscopy and
      electron energy loss spectroscopy. The titanium oxides were found to occur as
      nanoparticle aggregates with a predominant 3+ charge and amorphous microtubes
      when fabricated under an average power density of ca. 1 * 108W/cm2 and 1011W/cm2,
      respectively followed by dwelling in water. The crystalline colloidal particles
      have a relatively high content of Ti2+ and hence a lower minimum band gap of 3.4
      eV in comparison with 5.2 eV for the amorphous state. The protonation on both
      crystalline and amorphous phase caused defects, mainly titanium rather than
      oxygen vacancies and charge and/or volume-compensating defects. The hydrophilic
      nature and presumably varied extent of undercoordination at the free surface of
      the amorphous lamellae accounts for their rolling as tubes at water/air and
      water/glass interfaces. The nonstoichiometric titania thus fabricated have
      potential optoelectronic and catalytic applications in UV-visible range and shed
      light on the Ti charge and phase behavior of titania-water binary in natural
      shock occurrence.

PMID- 20672116
TI  - Avoiding Loss of Catalytic Activity of Pd Nanoparticles Partially Embedded in
      Nanoditches in SiC Nanowires.
AB  - Nanoditches from selective etching of periodically twinned SiC nanowires were
      employed to hinder the migration and coalescence of Pd nanoparticles supported on
      the nanowires, and thus to improve their catalytic stability for total combustion
      of methane. The results show that the etched Pd/SiC catalyst can keep the methane
      conversion of almost 100% while the unetched one has an obvious decline in the
      catalytic activity from 100 to 82% after ten repeated reaction cycles. The
      excellent catalytic stability originates from the limitation of the nanoditches
      to the migration and growth of Pd nanoparticles. 

PMID- 20672117
TI  - 3D Simulation of Nano-Imprint Lithography.
AB  - A proof of concept study of the feasibility of fully three-dimensional (3D) time
      dependent simulation of nano-imprint lithography of polymer melt, where the
      polymer is treated as a structured liquid, has been presented. Considering the
      flow physics of the polymer as a structured liquid, we have followed the line
      initiated by de Gennes, using a Molecular Stress Function model of the Doi and
      Edwards type. We have used a 3D Lagrangian Galerkin finite element methods
      implemented on a parallel computer architecture. In a Lagrangian techniques, the
      node point follows the particle movement, allowing for the movement of free
      surfaces or interfaces. We have extended the method to handle the dynamic
      movement of the contact line between the polymer melt and stamp during mold
      filling. 

PMID- 20672118
TI  - Localized surface plasmon resonance biosensing with large area of gold nanoholes
      fabricated by nanosphere lithography.
AB  - Localized surface plasmon resonance (LSPR) has been extensively studied as
      potential chemical and biological sensing platform due to its high sensitivity to
      local refractive index change induced by molecule adsorbate. Previous experiments
      have demonstrated the LSPR generated by gold nanoholes and its biosensing. Here,
      we realize large uniform area of nanoholes on scale of cm2 on glass substrate by
      nanosphere lithography which is essential for mass production. The morphology of
      the nanoholes is characterized using scanning electron microscope and atomic
      force microscope. The LSPR sensitivity of the nanoholes to local refractive index
      is measured to be 36 nm/RIU. However, the chip has demonstrated high sensitivity
      and specificity in biosensing: bovine serum albumin adsorption is detected with
      LSPR peak redshift of 27 nm, and biotin-streptavidin immunoassay renders a LSPR
      redshift of 11 nm. This work forms a foundation toward the cost-effective, high
      throughput, reliable and robust chip-based LSPR biosensor.

PMID- 20672119
TI  - Binding graphene sheets together using silicon: graphene/silicon superlattice.
AB  - We propose a superlattice consisting of graphene and monolayer thick Si sheets
      and investigate it using a first-principles density functional theory. The Si
      layer is found to not only strengthen the interlayer binding between the graphene
      sheets compared to that in graphite, but also inject electrons into graphene, yet
      without altering the most unique property of graphene: the Dirac fermion-like
      electronic structure. The superlattice approach represents a new direction for
      exploring basic science and applications of graphene-based materials.

PMID- 20672120
TI  - White Electroluminescence Using ZnO Nanotubes/GaN Heterostructure Light-Emitting
      Diode.
AB  - We report the fabrication of heterostructure white light-emitting diode (LED)
      comprised of n-ZnO nanotubes (NTs) aqueous chemically synthesized on p-GaN
      substrate. Room temperature electroluminescence (EL) of the LED demonstrates
      strong broadband white emission spectrum consisting of predominating peak centred
      at 560 nm and relatively weak violet-blue emission peak at 450 nm under forward
      bias. The broadband EL emission covering the whole visible spectrum has been
      attributed to the large surface area and high surface states of ZnO NTs produced
      during the etching process. In addition, comparison of the EL emission colour
      quality shows that ZnO nanotubes have much better quality than that of the ZnO
      nanorods. The colour-rendering index of the white light obtained from the
      nanotubes was 87, while the nanorods-based LED emit yellowish colour.

PMID- 20672121
TI  - Erratum to: Architectural Growth of Cu Nanoparticles Through Electrodeposition.
AB  - [This corrects the article DOI: 10.1007/s11671-009-9424-5.].

PMID- 20672122
TI  - Synthesis and enhanced field-emission of thin-walled, open-ended, and well
      aligned N-doped carbon nanotubes.
AB  - Thin-walled, open-ended, and well-aligned N-doped carbon nanotubes (CNTs) on the
      quartz slides were synthesized by using acetonitrile as carbon sources. As
      obtained products possess large thin-walled index (TWI, defined as the ratio of
      inner diameter and wall thickness of a CNT). The effect of temperature on the
      growth of CNTs using acetonitrile as the carbon source was also investigated. It
      is found that the diameter, the TWI of CNTs increase and the Fe encapsulation in
      CNTs decreases as the growth temperature rises in the range of 780-860 degrees C.
      When the growth temperature is kept at 860 degrees C, CNTs with TWI = 6.2 can be
      obtained. It was found that the filed-emission properties became better as CNT
      growth temperatures increased from 780 to 860 degrees C. The lowest turn-on and
      threshold field was 0.27 and 0.49 V/MUm, respectively. And the best field
      enhancement factors reached 1.09 * 105, which is significantly improved about an
      order of magnitude compared with previous reports. In this study, about 30 * 50
      mm2 free-standing film of thin-walled open-ended well-aligned N-doped carbon
      nanotubes was also prepared. The free-standing film can be transferred easily to
      other substrates, which would promote their applications in different fields.

PMID- 20672124
TI  - Growth of In2O3 Nanowires Catalyzed by Cu via a Solid-Liquid-Solid Mechanism.
AB  - In2O3 nanowires that are 10-50 nm in diameter and several hundred nanometers to
      micrometers in length have been synthesized by simply annealing Cu-In compound at
      a relatively low temperature of 550 degrees C. The catalysis of Cu on the growth
      of In2O3 nanowires is investigated. It is believed that the growth of In2O3
      nanowires is via a solid-liquid-solid (SLS) mechanism. Moreover,
      photoluminescence (PL) peaks of In2O3 nanowires at 412 and 523 nm were observed
      at room temperature, and their mechanism is also discussed.

PMID- 20672123
TI  - A novel quantum dots-based point of care test for syphilis.
AB  - One-step lateral flow test is recommended as the first line screening of
      syphilis for primary healthcare settings in developing countries. However, it
      generally shows low sensitivity. We describe here the development of a novel
      fluorescent POC (Point Of Care) test method to be used for screening for
      syphilis. The method was designed to combine the rapidness of lateral flow test
      and sensitiveness of fluorescent method. 50 syphilis-positive specimens and 50
      healthy specimens conformed by Treponema pallidum particle agglutination (TPPA)
      were tested with Quantum Dot-labeled and colloidal gold-labeled lateral flow test
      strips, respectively. The results showed that both sensitivity and specificity of
      the quantum dots-based method reached up to 100% (95% confidence interval [CI],
      91-100%), while those of the colloidal gold-based method were 82% (95% CI, 68
      91%) and 100% (95% CI, 91-100%), respectively. In addition, the naked-eye
      detection limit of quantum dot-based method could achieve 2 ng/ml of anti-TP47
      polyclonal antibodies purified by affinity chromatography with TP47 antigen,
      which was tenfold higher than that of colloidal gold-based method. In conclusion,
      the quantum dots were found to be suitable for labels of lateral flow test strip.
      Its ease of use, sensitiveness and low cost make it well-suited for population
      based on-the-site syphilis screening.

PMID- 20672125
TI  - Fabrication of a Highly Sensitive Chemical Sensor Based on ZnO Nanorod Arrays.
AB  - We report a novel method for fabricating a highly sensitive chemical sensor based
      on a ZnO nanorod array that is epitaxially grown on a Pt-coated Si substrate,
      with a top-top electrode configuration. To practically test the device, its O(2)
      and NO(2) sensing properties were investigated. The gas sensing properties of
      this type of device suggest that the approach is promising for the fabrication of
      sensitive and reliable nanorod chemical sensors.

PMID- 20672126
TI  - Nanocasting Synthesis of Ultrafine WO3 Nanoparticles for Gas Sensing
      Applications.
AB  - Ultrafine WO3 nanoparticles were synthesized by nanocasting route, using
      mesoporous SiO2 as a template. BET measurements showed a specific surface area of
      700 m 2/gr for synthesized SiO2, while after impregnation and template removal,
      this area was reduced to 43 m 2/gr for WO3 nanoparticles. HRTEM results showed
      single crystalline nanoparticles with average particle size of about 5 nm
      possessing a monoclinic structure, which is the favorite crystal structure for
      gas sensing applications. Gas sensor was fabricated by deposition of WO3
      nanoparticles between electrodes via low frequency AC electrophoretic deposition.
      Gas sensing measurements showed that this material has a high sensitivity to very
      low concentrations of NO2 at 250 degrees C and 300 degrees C.

PMID- 20672127
TI  - Hydrothermally Grown ZnO Micro/Nanotube Arrays and Their Properties.
AB  - We reported the optical and wettability properties of aligned zinc oxide
      micro/nanotube arrays, which were synthesized on zinc foil via a simple
      hydrothermal method. As-synthesized ZnO micro/nanotubes have uniform growth
      directions along the [0001] orientations with diameters in the range of 100-700
      nm. These micro/nanotubes showed a strong emission peak at 387 nm and two weak
      emission peaks at 422 and 485 nm, respectively, and have the hydrophobic
      properties with a contact angle of 121 degrees . Single ZnO micro/nanotube-based
      field-effect transistor was also fabricated, which shows typical n-type
      semiconducting behavior.

PMID- 20672128
TI  - Oxygen absorption in free-standing porous silicon: a structural, optical and
      kinetic analysis.
AB  - Porous silicon (PSi) is a nanostructured material possessing a huge surface area
      per unit volume. In consequence, the adsorption and diffusion of oxygen in PSi
      are particularly important phenomena and frequently cause significant changes in
      its properties. In this paper, we study the thermal oxidation of p+-type free
      standing PSi fabricated by anodic electrochemical etching. These free-standing
      samples were characterized by nitrogen adsorption, thermogravimetry, atomic force
      microscopy and powder X-ray diffraction. The results show a structural phase
      transition from crystalline silicon to a combination of cristobalite and quartz,
      passing through amorphous silicon and amorphous silicon-oxide structures, when
      the thermal oxidation temperature increases from 400 to 900  degrees C. Moreover,
      we observe some evidence of a sinterization at 400  degrees C and an optimal
      oxygen-absorption temperature about 700  degrees C. Finally, the UV/Visible
      spectrophotometry reveals a red and a blue shift of the optical transmittance
      spectra for samples with oxidation temperatures lower and higher than 700 
      degrees C, respectively.

PMID- 20672129
TI  - Friction and shear strength at the nanowire-substrate interfaces.
AB  - The friction and shear strength of nanowire (NW)-substrate interfaces critically
      influences the electrical/mechanical performance and life time of NW-based
      nanodevices. Yet, very few reports on this subject are available in the
      literature because of the experimental challenges involved and, more specifically
      no studies have been reported to investigate the configuration of individual NW
      tip in contact with a substrate. In this letter, using a new experimental method,
      we report the friction measurement between a NW tip and a substrate for the first
      time. The measurement was based on NW buckling in situ inside a scanning electron
      microscope. The coefficients of friction between silver NW and gold substrate and
      between ZnO NW and gold substrate were found to be 0.09-0.12 and 0.10-0.15,
      respectively. The adhesion between a NW and the substrate modified the true
      contact area, which affected the interfacial shear strength. Continuum mechanics
      calculation found that interfacial shear strengths between silver NW and gold
      substrate and between ZnO NW and gold substrate were 134-139 MPa and 78.9-95.3
      MPa, respectively. This method can be applied to measure friction parameters of
      other NW-substrate systems. Our results on interfacial friction and shear
      strength could have implication on the AFM three-point bending tests used for
      nanomechanical characterisation.

PMID- 20672130
TI  - A two-dimensional electron gas as a sensitive detector for time-resolved
      tunneling measurements on self-assembled quantum dots.
AB  - A two-dimensional electron gas (2DEG) situated nearby a single layer of self
      assembled quantum dots (QDs) in an inverted high electron mobility transistor
      (HEMT) structure is used as a detector for time-resolved tunneling measurements.
      We demonstrate a strong influence of charged QDs on the conductance of the 2DEG
      which allows us to probe the tunneling dynamics between the 2DEG and the QDs time
      resolved. Measurements of hysteresis curves with different sweep times and real
      time conductance measurements in combination with an boxcar-like evaluation
      method enables us to unambiguously identify the transients as tunneling events
      between the s- and p-electron QD states and the 2DEG and rule out defect-related
      transients.

PMID- 20672131
TI  - Synthesis and Magnetic Properties of Nearly Monodisperse CoFe2O4Nanoparticles
      Through a Simple Hydrothermal Condition.
AB  - Nearly monodisperse cobalt ferrite (CoFe2O4) nanoparticles without any size
      selection process have been prepared through an alluring method in an
      oleylamine/ethanol/water system. Well-defined nanospheres with an average size of
      5.5 nm have been synthesized using metal chloride as the law materials and oleic
      amine as the capping agent, through a general liquid-solid-solution (LSS)
      process. Magnetic measurement indicates that the particles exhibit a very high
      coercivity at 10 K and perform superparamagnetism at room temperature which is
      further illuminated by ZFC/FC curves. These superparamagnetic cobalt ferrite
      nanomaterials are considered to have potential application in the fields of
      biomedicine. The synthesis method is possible to be a general approach for the
      preparation of other pure binary and ternary compounds.

PMID- 20672132
TI  - Structure and luminescence properties of eu3+-doped cubic mesoporous silica thin
      films.
AB  - Eu3+ ions-doped cubic mesoporous silica thin films with a thickness of about 205
      nm were prepared on silicon and glass substrates using triblock copolymer as a
      structure-directing agent using sol-gel spin-coating and calcination processes. X
      ray diffraction and transmission electron microscopy analysis show that the
      mesoporous silica thin films have a highly ordered body-centered cubic mesoporous
      structure. High Eu3+ ion loading and high temperature calcination do not destroy
      the ordered cubic mesoporous structure of the mesoporous silica thin films.
      Photoluminescence spectra show two characteristic emission peaks corresponding to
      the transitions of5D0-7F1 and 5D0-7F2 of Eu3+ ions located in low symmetry sites
      in mesoporous silica thin films. With the Eu/Si molar ratio increasing to 3.41%,
      the luminescence intensity of the Eu3+ ions-doped mesoporous silica thin films
      increases linearly with increasing Eu3+ concentration.

PMID- 20672133
TI  - Resonant Tunneling in Photonic Double Quantum Well Heterostructures.
AB  - Here, we study the resonant photonic states of photonic double quantum well
      (PDQW) heterostructures composed of two different photonic crystals. The
      heterostructure is denoted as B/A/B/A/B, where photonic crystals A and B act as
      photonic wells and barriers, respectively. The resulting band structure causes
      photons to become confined within the wells, where they occupy discrete quantized
      states. We have obtained an expression for the transmission coefficient of the
      PDQW heterostructure using the transfer matrix method and have found that
      resonant states exist within the photonic wells. These resonant states occur in
      split pairs, due to a coupling between degenerate states shared by each of the
      photonic wells. It is observed that when the resonance energy lies at a bound
      photonic state and the two photonic quantum wells are far away from each other,
      resonant states appear in the transmission spectrum of the PDQW as single peaks.
      However, when the wells are brought closer together, coupling between bound
      photonic states causes an energy-splitting effect, and the transmitted states
      each have two peaks. Essentially, this means that the system can be switched
      between single and double transparent states. We have also observed that the
      total number of resonant states can be controlled by varying the width of the
      photonic wells, and the quality factor of transmitted peaks can be drastically
      improved by increasing the thickness of the outer photonic barriers. It is
      anticipated that the resonant states described here can be used to develop new
      types of photonic-switching devices, optical filters, and other optoelectronic
      devices.

PMID- 20672134
TI  - The nature of surface oxides on corrosion-resistant nickel alloy covered by
      alkaline water.
AB  - A nickel alloy with high chrome and molybdenum content was found to form a
      highly resistive and passive oxide layer. The donor density and mobility of ions
      in the oxide layer has been determined as a function of the electrical potential
      when alkaline water layers are on the alloy surface in order to account for the
      relative inertness of the nickel alloy in corrosive environments.

PMID- 20672135
TI  - Low-cost flexible nano-sulfide/carbon composite counter electrode for quantum-dot
      sensitized solar cell.
AB  - Cu2S nanocrystal particles were in situ deposited on graphite paper to prepare
      nano-sulfide/carbon composite counter electrode for CdS/CdSe quantum-dot
      sensitized solar cell (QDSC). By optimization of deposition time, photovoltaic
      conversion efficiency up to 3.08% was obtained. In the meantime, this composite
      counter electrode was superior to the commonly used Pt, Au and carbon counter
      electrodes. Electrochemical impedance spectra further confirmed that low charge
      transfer resistance at counter electrode/electrolyte interface was responsible
      for this, implied the potential application of this composite counter electrode
      in high-efficiency QDSC.

PMID- 20672136
TI  - Stable Field Emitters for a Miniature X-ray Tube Using Carbon Nanotube Drop
      Drying on a Flat Metal Tip.
AB  - Stable carbon nanotube (CNT) field emitters for a vacuum-sealed miniature X-ray
      tube have been fabricated. The field emitters with a uniform CNT coating are
      prepared by a simple drop drying of a CNT mixture solution that is composed of
      chemically modified multi-walled CNTs, silver nanoparticles, and isopropyl
      alcohol on flat tungsten tips. A highly thermal- and electrical-conductive silver
      layer strongly attaches CNTs to the tungsten tips. Consequently, the field
      emitters exhibit good electron emission stability: continuous electron emission
      of around 100 MUA at 2.3 V/MUm has stably lasted over 40 h even at non-high
      vacuum ambient (~10-3 Pa).

PMID- 20672137
TI  - Initial Growth of Single-Crystalline Nanowires: From 3D Nucleation to 2D Growth.
AB  - The initial growth stage of the single-crystalline Sb and Co nanowires with
      preferential orientation was studied, which were synthesized in porous anodic
      alumina membranes by the pulsed electrodeposition technique. It was revealed that
      the initial growth of the nanowires is a three-dimensional nucleation process,
      and then gradually transforms to two-dimensional growth via progressive
      nucleation mechanism, which resulting in a structure transition from
      polycrystalline to single crystalline. The competition among the nuclei inside
      the nanoscaled-confined channel and the growth kinetics is responsible for the
      structure transition of the initial grown nanowires.

PMID- 20672138
TI  - Side-by-Side In(OH)(3) and In(2)O(3) Nanotubes: Synthesis and Optical Properties.
AB  - A simple and mild wet-chemical approach was developed for the synthesis of one
      dimensional (1D) In(OH)(3) nanostructures. By calcining the 1D In(OH)(3)
      nanocrystals in air at 250 degrees C, 1D In(2)O(3) nanocrystals with the same
      morphology were obtained. TEM results show that both 1D In(OH)(3) and 1D
      In(2)O(3) are composed of uniform nanotube bundles. SAED and XRD patterns
      indicate that 1D In(OH)(3) and 1D In(2)O(3) nanostructures are single crystalline
      and possess the same bcc crystalline structure as the bulk In(OH)(3) and
      In(2)O(3), respectively. TGA/DTA analyses of the precursor In(OH)(3) and the
      final product In(2)O(3) confirm the existence of CTAB molecules, and its content
      is about 6%. The optical absorption band edge of 1D In(2)O(3) exhibits an evident
      blueshift with respect to that of the commercial In(2)O(3) powders, which is
      caused by the increasing energy gap resulted from decreasing the grain size. A
      relatively strong and broad purple-blue emission band centered at 440 nm was
      observed in the room temperature PL spectrum of 1D In(2)O(3) nanotube bundles,
      which was mainly attributed to the existence of the oxygen vacancies.

PMID- 20672139
TI  - Dysprosium-catalyzed growth of single-walled carbon nanotube arrays on
      substrates.
AB  - In this letter, we report that dysprosium is an effective catalyst for single
      walled carbon nanotubes (SWNTs) growth via a chemical vapor deposition (CVD)
      process for the first time. Horizontally superlong well-oriented SWNT arrays on
      SiO2/Si wafer can be fabricated by EtOH-CVD under suitable conditions. The
      structure and properties are characterized by scanning electron microscopy,
      transition electron microscopy, Raman spectroscopy and atomic force microscopy.
      The results show that the SWNTs from dysprosium have better structural uniformity
      and better conductivity with fewer defects. This rare earth metal provides not
      only an alternative catalyst for SWNTs growth, but also a possible method to
      generate high percentage of superlong semiconducting SWNT arrays for various
      applications of nanoelectronic device.

PMID- 20672140
TI  - In Situ Confocal Raman Mapping Study of a Single Ti-Assisted ZnO Nanowire.
AB  - In this work, we succeeded in preparing in-plane zinc oxide nanowires using a Ti
      grid assisted by the chemical vapor deposition method. Optical spatial mapping of
      the Confocal Raman spectra was used to investigate the phonon and geometric
      properties of a single ZnO nanowire. The local optical results reveal a red shift
      in the non-polar E2 high frequency mode and width broadening along the growth
      direction, reflecting quantum-confinement in the radial direction.

PMID- 20672141
TI  - Well-aligned Nickel Nanochains Synthesized by a Template-free Route.
AB  - Highly uniform and well-aligned one-dimensional Ni nanochains with controllable
      diameters, including 33, 78, and 120 nm, have been synthesized by applying an
      external magnetic field without any surface modifying agent. The formation can be
      explained by the interactions of magnetic dipoles in the presence of applied
      magnetic field. Magnetic measurements demonstrate that the shape anisotropy
      dominates the magnetic anisotropy. The demagnetization factor, ?N, is in the
      range of 0.23-0.36.

PMID- 20672142
TI  - Nonlinear Rheology of Unentangled Polymer Melts Reinforced with High
      Concentration of Rigid Nanoparticles.
AB  - A scaling model is presented to analyze the nonlinear rheology of unentangled
      polymer melts filled with high concentration of small spherical particles.
      Assuming the majority of chains to be reversibly adsorbed to the surface of the
      particles, we show that the emergence of nonlinearity in the viscoelastic
      response of the composite system subjected to a 2D shear flow results from
      stretching of the adsorbed chains and increasing desorption rate of the adsorbed
      segments due to the imposed deformation. The steady-state shear viscosity of the
      mixture in nonlinear shear thinning regime follows the power law eta ~ gamma(
      1/2) where gamma is the applied shear rate. At large strain amplitude gamma(0,)
      the storage and loss moduli in strain sweep tests scale as G' ~ gamma(0)(-1) and
      G" ~ gamma(0)(-1/2) respectively.

PMID- 20672143
TI  - Thermal Evaporation Synthesis and Properties of ZnO Nano/Microstructures Using
      Carbon Group Elements as the Reducing Agents.
AB  - ZnO nano/microstructures have been formed by thermal evaporation method using
      ZnO powders mixed with carbon group elements (C, Si, Ge, Sn, or Pb) as the
      reducing agent. For cases of mixed precursors of ZnO/C, ZnO/Si, and ZnO/Ge, the
      pure ZnO nano/microstructures are realized, while for ZnO/Sn (ZnO/Pb) systems,
      the phase of Pb2O3(Zn2SnO4) generally are represented in the ZnO products. The
      appearance of Pb2O3(Zn2SnO4) is attributed to the lower melting point and higher
      vapor pressure of Sn (Pb) in the heating and evaporation processes. The
      morphologies and sizes of the products are controlled by adjusting the growth
      regions and/or introducing gaseous argon. Room temperature (RT) photoluminescence
      spectra indicate that the intensity (peak position) of the ultraviolet emission
      is increased (redshift) due to the existence of Zn2SnO4 phase in the ZnO
      products. The Pb2O3(Zn2SnO4) phase in ZnO nano/microstructures plays a important
      role in enhancing the saturation magnetizations of RT ferromagnetism with respect
      to the case of pure ZnO products fabricated by the precursor of mixed ZnO and
      graphite.

PMID- 20672144
TI  - Evaluating the suitability of using rat models for preclinical efficacy and side
      effects with inhaled corticosteroids nanosuspension formulations.
AB  - Inhaled corticosteroids (ICS) are often prescribed as first-line therapy for
      patients with asthma Despite their efficacy and improved safety profile compared
      with oral corticosteroids, the potential for systemic side effects continues to
      cause concern. In order to reduce the potential for systemic side effects, the
      pharmaceutical industry has begun efforts to generate new drugs with pulmonary
      targeted topical efficacy. One of the major challenges of this approach is to
      differentiate both efficacy and side effects (pulmonary vs. systemic) in a
      preclinical animal model. In this study, fluticasone and ciclesonide were used as
      tool compounds to explore the possibility of demonstrating both efficacy and side
      effects in a rat model using pulmonary delivery via intratracheal (IT)
      instillation with nanosuspension formulations. The inhibition of neutrophil
      infiltration into bronchoalveolar lavage fluid (BALF) and cytokine (TNFalpha)
      production were utilized to assess pulmonary efficacy, while adrenal and thymus
      involution as well as plasma corticosterone suppression was measured to assess
      systemic side effects. Based on neutrophil infiltration and cytokine production
      data, the ED50s for ciclesonide and fluticasone were calculated to be 0.1 and
      0.03 mg, respectively. At the ED50, the average adrenal involution was 7.6 +/-
      5.3% for ciclesonide versus 16.6 +/- 5.1% for fluticasone, while the average
      thymus involution was 41.0 +/- 4.3% for ciclesonide versus 59.5 +/- 5.8% for
      fluticasone. However, the differentiation became less significant when the dose
      was pushed to the EDmax (0.3 mg for ciclesonide, 0.1 mg for fluticasone).
      Overall, the efficacy and side effect profiles of the two compounds exhibited
      differentiation at low to mid doses (0.03-0.1 mg ciclesonide, 0.01-0.03 mg
      fluticasone), while this differentiation diminished at the maximum efficacious
      dose (0.3 mg ciclesonide, 0.1 mg fluticasone), likely due to overdosing in this
      model. We conclude that the rat LPS model using IT administration of
      nanosuspensions of ICS is a useful tool to demonstrate pulmonary-targeted
      efficacy and to differentiate the side effects. However, it is only suitable at
      sub-maximum efficacious levels.

PMID- 20672145
TI  - Nanocomposite ZnO-SnO2 Nanofibers Synthesized by Electrospinning Method.
AB  - We report the characterization of mixed oxides nanocomposite nanofibers of (1 -
      x) ZnO-(x)SnO2 (x <= 0.45) synthesized by electrospinning technique. The diameter
      of calcined nanofibers depends on Sn content. Other phases like SnO, ZnSnO3, and
      Zn2SnO4 were absent. Photoluminescence studies show that there is a change in the
      blue/violet luminescence confirming the presence of Sn in Zn-rich composition.
      Present study shows that the crystalline nanocomposite nanofibers with
      stoichiometry of (1 - x)ZnO-(x)SnO2 (x <= 0.45) stabilize after the calcination
      and possess some morphological and optical properties that strongly depend on Sn
      content.

PMID- 20672146
TI  - 10th anniversary issue: Switzerland.

PMID- 20672148
TI  - Probing nucleobase mismatch variations by electrochemical techniques: exploring
      the effects of position and nature of the single-nucleotide mismatch.
AB  - Electrochemical impedance spectroscopy (EIS) has been used as an ultrasensitive
      tool for label-free detection of single-nucleotide mismatches in double-stranded
      DNA (ds-DNA) films. In this study, we have explored the effects of the position
      and of the type of single-nucleotide mismatch in ds-DNA on gold surfaces and were
      able to distinguish mismatch positions and mismatch pairs. The single-nucleotide
      mismatches A-C, A-A and A-G were introduced at three positions within the
      sequence in bottom, middle and top positions of ds-DNA, the films were studied by
      EIS, and the impedance results were interpreted with the help of equivalent
      circuits. The DeltaR(ct), the difference in charge transfer resistance before and
      after the addition of Zn(2+), was used to distinguish single-nucleotide mismatch
      within the DNA sequences. Importantly, the mismatch pair is easily
      distinguishable at the middle position. A purine-pyrimidine mismatch can be
      distinguished from purine-purine mismatch by its lower DeltaR(ct) value. In
      addition, all ds-DNA films were studied by scanning electrochemical microscopy in
      the absence and presence of Zn(2+), allowing us to distinguish a range of
      mismatched films from matched ds-DNA film.

PMID- 20672150
TI  - "Cloud" assemblies: quantum dots form electrostatically bound dynamic nebulae
      around large gold nanoparticles.
AB  - Dynamic self-assembled structures of nanoparticles can be produced using
      predominantly electrostatic interactions. Such assemblies were made from large,
      positively charged Au metal nanoparticles surrounded by an electrostatically
      bound cloud of smaller, negatively charged CdSe/ZnS or CdTe quantum dots. At low
      concentrations they are topologically similar to double electric layers of ions
      and corona-like assemblies linked by polymer chains. They can also be compared to
      the topological arrangement of some planetary systems in space. The great
      advantages of the cloud assemblies are (1) their highly dynamic nature compared
      to more rigid covalently bound assemblies, (2) simplicity of preparation, and (3)
      exceptional versatility in components and resulting optical properties.
      Photoluminescence intensity enhancement originating from quantum resonance
      between excitons and plasmons was observed for CdSe/ZnS quantum dots, although
      CdTe dots displayed emission quenching. To evaluate more attentively their
      dynamic behavior, emission data were collected for the cloud-assemblies with
      different ratios of the components and ionic strengths of the media. The emission
      of the system passes through a maximum for 80 QDs ? 1 Au NP as determined by the
      structure of the assemblies and light absorption conditions. Ionic strength
      dependence of luminescence intensity contradicts the predictions based on the
      Gouy-Chapman theory and osmotic pressure at high ionic strengths due to formation
      of larger chaotic colloidally stable assemblies. "Cloud" assemblies made from
      different nanoscale components can be used both for elucidation of most
      fundamental aspects of nanoparticle interactions, as well as for practical
      purposes in sensing and biology.

PMID- 20672151
TI  - Click-xylosides mitigate glioma cell invasion in vitro.
AB  - Tumor related invasion allows cancers to spread beyond tissue boundaries and
      significantly affects patient prognosis. In this study we show that several click
      xylosides markedly inhibit the invasive capability of a highly invasive glioma
      cell line in vitro. These novel xylosides are promising chemical biology tools to
      probe the role of the proteoglycan glycome in regulating tumor biology.

PMID- 20672152
TI  - Double layer in room temperature ionic liquids: influence of temperature and
      ionic size on the differential capacitance and electrocapillary curves.
AB  - Differential capacity-potential curves, C(E), were obtained from electrochemical
      impedance spectra (12 kHz-2 Hz) for the interfaces between Hg and a series of
      alkyl imidazolium-based room temperature ionic liquids having the same anion,
      bis(trifluoromethanesulfonyl) imide: 1-ethyl-3-methylimidazolium
      bis(trifluoromethanesulfonyl) imide [EMIM][Tf(2)N], 1-butyl-3-methylimidazolium
      bis(trifluoromethanesulfonyl) imide [BMIM][Tf(2)N], 1-hexyl-3-methylimidazolium
      bis(trifluoromethanesulfonyl) imide [HMIM][Tf(2)N]. The electrocapillary curves
      were obtained from drop time measurements and the values of the pzc were
      calculated. The pzc apparently becomes more negative as the imidazolium alkyl
      chain length increases. A small effect of the cation is seen on the C(E) curves
      at negative potentials. The effect of the aromatic nature of the cation is
      assessed by comparing 1-butyl-1-methylimidazolium bis(trifluoromethanesulfonyl)
      imide, with 1-butyl-3-methylpyrrolidinium bis(trifluoromethanesulfonyl) imide
      [BMPyr][Tf(2)N]. The effects of temperature on the capacitance, drop time
      electrocapillary curve and on the pzc were also obtained. The capacity was found
      to increase with increasing temperature in the whole range of accessible
      potentials.

PMID- 20672149
TI  - A bird's-eye view of post-translational modifications in the spliceosome and
      their roles in spliceosome dynamics.
AB  - Pre-mRNA splicing, the removal of noncoding intron sequences from the pre-mRNA,
      is a critical reaction in eukaryotic gene expression. Pre-mRNA splicing is
      carried out by a remarkable macromolecular machine, the spliceosome, which
      undergoes dynamic rearrangements of its RNA and protein components to assemble
      its catalytic center. While significant progress has been made in describing the
      "moving parts" of this machine, the mechanisms by which spliceosomal proteins
      mediate the ordered rearrangements within the spliceosome remain elusive. Here we
      explore recent evidence from proteomics studies revealing extensive post
      translational modification of splicing factors. While the functional significance
      of most of these modifications remains to be characterized, we describe recent
      studies in which the roles of specific post-translational modifications of
      splicing factors have been characterized. These examples illustrate the
      importance of post-translational modifications in spliceosome dynamics.

PMID- 20672153
TI  - Role of the reagents consumption in the chaotic dynamics of the Belousov
      Zhabotinsky oscillator in closed unstirred reactors.
AB  - Chemical oscillations generated by the Belousov-Zhabotinsky reaction in batch
      unstirred reactors, show a characteristic chaotic transient in their dynamical
      regime, which is generally found between two periodic regions. Chemical chaos
      starts and finishes by following a direct and an inverse Ruelle-Takens-Newhouse
      scenario, respectively. In previous works we showed, both experimentally and
      theoretically, that the complex oscillations are generated by the coupling among
      the nonlinear kinetics and the transport phenomena, the latter due to
      concentration and density gradients. In particular, convection was found to play
      a fundamental role. In this paper, we develop a reaction-diffusion-convection
      model to explore the influence of the reagents consumption (BrO in particular) in
      the inverse transition from chaos to periodicity. We demonstrated that, on the
      route towards thermodynamic equilibrium, the reagents concentration directly
      modulates the strength of the coupling between chemical kinetics and mass
      transport phenomena. An effective sequential decoupling (reaction-diffusion
      convection --> reaction-diffusion --> reaction) takes place upon the reagents
      consumption and this is at the basis of the transition from chaos to periodicity.

PMID- 20672154
TI  - Diastereoselective hydrophosphonylation of imines using (R,R)-TADDOL phosphite.
      Asymmetric synthesis of alpha-aminophosphonic acid derivatives.
AB  - Efficient synthesis of alpha-aminophosphonic acid derivatives is achieved, the
      key step being a diastereoselective hydrophosphonylation of N-diphenylphosphinyl
      imines using a readily available chiral cyclic (R,R)-TADDOL-phosphite derived
      from inexpensive natural tartaric acid.

PMID- 20672155
TI  - Synthesis of 5,6-dihydropyrrolo[2,1-a]isoquinolines featuring an intramolecular
      radical-oxidative cyclization of polysubstituted pyrroles, and evaluation of
      their cytotoxic activity.
AB  - A three-step protocol for the synthesis of 1,2,3,8,9-pentasubstituted-5,6
      dihydropyrrolo[2,1-a]isoquinolines is described, using van Leusen's
      polysubstituted pyrrole construction followed by intramolecular radical-oxidative
      cyclization of the isoquinoline system. The cytotoxic activities of the
      dihydropyrroloisoquinolines were tested on six tumor cell lines. Preliminary
      structure-activity studies revealed the importance of the identity of the
      aromatic substituent at the C-2 position, particularly a phenyl, m-(amino) phenyl
      or m-(cyclohexylmethylpiperazinamide) phenyl substituent, for cytotoxic activity.

PMID- 20672156
TI  - LD spectroscopy of natural and synthetic biomaterials.
AB  - The structural characterization of biomaterials is challenging because they are
      usually too large for NMR or high resolution mass spectrometry and not well
      enough structured for X-ray crystallography. Structural characterization and
      kinetic analysis for such systems thus has to proceed by collecting complementary
      data from a wide range of different techniques. This tutorial review describes
      how linear dichroism, a polarized absorbance spectroscopy technique applied to
      oriented molecular systems, can be used to provide useful data on biomaterials.
      In particular LD can provide information about relative orientations of sub-units
      of biomaterials and orientations of the whole biomaterial with respect to an
      orientation axis. An outline of linear dichroism and a summary of the artifacts
      to be avoided are followed by a description of how Couette flow linear dichroism
      has been used for a range of biomaterial systems including: DNA; DNA:ligand
      systems; cytoskeletal fibrous proteins; synthetic protein fibres; membrane
      proteins in liposomes; bacteriophage; carbon nanotubes; and peptidoglycan
      systems.

PMID- 20672157
TI  - Atomistic details of the associative phosphodiester cleavage in human
      ribonuclease H.
AB  - During translation of the genetic information of DNA into proteins, mRNA is
      synthesized by RNA polymerase and after the transcription process degraded by
      RNase H. The endoribonuclease RNase H is a member of the nucleotidyl-transferase
      (NT) superfamily and is known to hydrolyze the phosphodiester bonds of RNA which
      is hybridized to DNA. Retroviral RNase H is part of the viral reverse
      transcriptase enzyme that is indispensable for the proliferation of retroviruses,
      such as HIV. Inhibitors of this enzyme could therefore provide new drugs against
      diseases like AIDS. In our study we investigated the molecular mechanism of RNA
      cleavage by human RNase H using a comprehensive high level DFT/B3LYP QM/MM
      theoretical method for the calculation of the stationary points and nudged
      elastic band (NEB) and free energy calculations to identify the transition state
      structures, the rate limiting step and the reaction barrier. Our calculations
      reveal that the catalytic mechanism proceeds in two steps and that the nature of
      the nucleophile is a water molecule. In the first step, the water attack on the
      scissile phosphorous is followed by a proton transfer from the water to the O2P
      oxygen and a trigonal bipyramidal pentacoordinated phosphorane is formed.
      Subsequently, in the second step the proton is shuttled to the O3' oxygen to
      generate the product state. During the reaction mechanism two Mg(2+) ions support
      the formation of a stable associated in-line S(N)2-type phosphorane intermediate.
      Our calculated energy barrier of 19.3 kcal mol(-1) is in excellent agreement with
      experimental findings (20.5 kcal mol(-1)). These results may contribute to the
      clarification and understanding of the RNase H reaction mechanism and of further
      enzymes from the RNase family.

PMID- 20672158
TI  - Sulfide sensor based on the room-temperature phosphorescence of ZnO/SiO2
      nanocomposite.
AB  - An environmentally friendly sulfide sensor based on the room-temperature
      phosphorescence (RTP) of the ZnO/SiO(2) nanocomposite has been developed. The
      ZnO/SiO(2) nanocomposite prepared by the sol-gel route produces highly emissive
      broadband RTP which can be clearly observed by the naked eye. The phosphorescence
      intensity monitored at 460 nm (excitation at 320 nm) decreases with increasing
      sulfide ions concentrations. The response behavior of the sensor is dependent on
      the pH value of the solution. At pH 10, the sensor shows a good, linear response
      to sulfide from 4.88 x 10(-5) to 1.02 x 10(-2) M with a detection limit of 1.64 x
      10(-6) M (3sigma). It has been successfully applied to the determination of
      sulfide in spiked water and wastewater. Furthermore, this sensor can be
      regenerated by dipping it into an H(2)O(2) solution. The mechanisms for the RTP
      detection of sulfide based on the ZnO/SiO(2) nanocomposite and the sensor
      regeneration by H(2)O(2) are proposed.

PMID- 20672159
TI  - Minimally invasive monitoring of cellulose degradation by desorption electrospray
      ionization and laser ablation electrospray ionization mass spectrometry.
AB  - Minimally invasive desorption electrospray ionization-mass spectrometry (DESI-MS)
      and laser ablation electrospray ionization-MS (LAESI-MS) were used to look for
      soluble cellulose degradation products produced by accelerated aging in unsized
      cotton paper. Soluble extracts from papers aged 144 to 26,856 hours were first
      analyzed in solution using traditional electrospray ionization-MS (ESI-MS).
      Results were compared to those from direct analysis of condensed phase
      degradation products extracted from the absorbent paper substrate using DESI-MS
      and LAESI-MS. ESI-MS results showed evidence of oligosaccharide degradation
      products ranging from cellobiose to cellononaose; using DESI-MS and LAESI-MS,
      products from cellobiose to cellodecaose and glucose to cellooctaose,
      respectively, were observed. As degradation proceeded, increased quantities of
      both low and high molecular weight oligosaccharides were observed. The analytical
      approaches developed in the control study were applied for the detection of
      degradation products in two naturally-aged books dating from the 19th century,
      both made from cotton and linen. Oligosaccharides ranging from glucose to
      cellopentaose were observed.

PMID- 20672160
TI  - A third generation glucose biosensor based on cellobiose dehydrogenase from
      Corynascus thermophilus and single-walled carbon nanotubes.
AB  - A third generation glucose biosensor working under physiological conditions with
      a linear range of 0.1-30 mM, a detection limit of 0.05 mM, and a sensitivity of
      222 nA uM(-1) cm(-2) has been developed by co-adsorption of cellobiose
      dehydrogenase (CDH) from the ascomycete Corynascus thermophilus (CtCDH) and
      oxidatively shortened single-walled carbon nanotubes (SWCNTs).

PMID- 20672161
TI  - Ultrasound-assisted design of metal nanocomposites.
AB  - A one-step method was developed to produce metal nanocomposites from metal alloys
      under ultrasound irradiation. Systematic investigation of ultrasound effects on
      various metal particles reveals cavitation-induced recrystallization and
      oxidation of metals as main factors in the process. The fact that different
      metals react in dramatically different fashion towards ultrasound irradiation was
      exploited for the formation of nanoscale composites. Results from the application
      of ultrasound to formation of nanocatalysts are reported.

PMID- 20672162
TI  - Enhancing the stability of metal-organic frameworks in humid air by incorporating
      water repellent functional groups.
AB  - We report a modular construction of a new metal-organic framework (MOF) by
      strategically incorporating a number of water repellent functional groups in the
      frameworks. These MOFs demonstrate both open structure for high sorption
      capability and strong water resistance.

PMID- 20672163
TI  - Monodispersed molecular donors for bulk hetero-junction solar cells: from
      molecular properties to device performances.
AB  - The relations between the chemical-physical properties of novel designed
      monodispersed donors and their photovoltaic performances are discussed. The
      importance of intermolecular interactions is emphasized to figure out the
      achievement of high performing bulk hetero-junction solar cells which are
      solution processed.

PMID- 20672164
TI  - Aptamer based reversible DNA induced hydrogel system for molecular recognition
      and separation.
AB  - An aptamer-based DNA strand, captured with a specific molecule from a multi
      species system, was used to initiate crosslinking of the hydrogel. The hydrogel
      can then be dissolved with a displacement of the DNA strand and the captured
      molecule can be released. Recognition and separation at the molecular level is
      thus achieved.

PMID- 20672165
TI  - Structure of the hydrated Ca(2+) and Cl(-): Combined X-ray absorption
      measurements and QM/MM MD simulations study.
AB  - A combination of X-ray absorption spectroscopy (XAS) measurements and quantum
      mechanical/molecular mechanical (QM/MM) molecular dynamics (MD) simulations has
      been applied to elucidate detailed information on the hydration structures of
      Ca(2+) and Cl(-). The XAS spectra (extended X-ray absorption fine structure,
      EXAFS, and X-ray absorption near-edge structure, XANES) measured from aqueous
      CaCl(2) solution were analyzed and compared to those generated from snapshots of
      QM/MM MD simulations of Ca(2+) and Cl(-) in water. With regard to this scheme,
      the simulated QM/MM-EXAFS and QM/MM-XANES spectra, which correspond to the local
      structure and geometrical arrangement of the hydrated Ca(2+) and Cl(-) at
      molecular level show good agreement with the experimentally observed EXAFS and
      XANES spectra. From the analyses of the simulated QM/MM-EXAFS spectra, the
      hydration numbers for Ca(2+) and Cl(-) were found to be 7.1 +/- 0.7 and 5.1 +/-
      1.3, respectively, compared to the corresponding values of 6.9 +/- 0.7 and 6.0 +/
      1.7 derived from the measured EXAFS data. In particular for XANES results, it is
      found that ensemble averages derived from the QM/MM MD simulations can provide
      reliable QM/MM-XANES spectra, which are strongly related to the shape of the
      experimental XANES spectra. Since there is no direct way to convert the measured
      XANES spectrum into details relating to geometrical arrangement of the hydrated
      ions, it is demonstrated that such a combined technique of XAS experiments and
      QM/MM MD simulations is well-suited for the structural verification of aqueous
      ionic solutions.

PMID- 20672166
TI  - Peptide and protein based materials in 2010: from design and structure to
      function and application.

PMID- 20672167
TI  - Series behavior of lanthanoid(III) complexes with the alpha-1-Wells-Dawson
      heteropolyoxoanion in acetonitrile: electrochemistry and Ln coordination.
AB  - The tetra-n-butylammonium (TBA(+)) salts for a series of lanthanoid(III) (Ln =
      Nd, Sm, Eu, Tb, Dy, Yb, and Y) complexes with the alpha-1-isomer of the Wells
      Dawson heteropolyoxoanion, alpha-1-[P(2)W(17)O(61)](10-), were prepared and
      characterized by voltammetry, controlled-potential bulk electrolysis, Eu L(3)
      edge XANES spectroelectrochemistry, and Ln L(3)-edge X-ray absorption
      spectroscopy. Aspects of the series behavior across the 4f period for the complex
      anions with nominal 1 : 1 Ln(III):alpha-1-[P(2)W(17)O(61)](10-) stoichiometries
      are detailed. The voltammetric response of the alpha-1 ligand alone in dry
      acetonitrile (with 0.1 M (TBA)PF(6) electrolyte) is concentration independent and
      remarkably well-defined with five waves attributable to W-based redox processes.
      The formation of heteropoly blue solutions upon electrochemical reduction results
      in chemical instabilities and isomerization. The deliberate addition of water
      turns an otherwise ideal response into a broad and poorly resolved one, wherein
      the first reduction process is shifted 150 mV to more positive electrode
      potentials. Upon its coordination with Ln(III) ions, the voltammetric response
      develops notable complexities with as many as ten concentration-dependent couples
      attributable to W-based redox processes of the Ln:alpha-1 complexes. The results
      from in situ Eu L(3)-edge XANES of the Eu(III):alpha-1 complex provide no
      evidence for the one-electron reduction of Eu(III) at controlled electrode
      potentials comparable to those that were previously found to form Eu(II) in the
      potassium salt of the corresponding Eu(III) complex upon reduction in an aqueous
      electrolyte. To explain the contrasting system behaviors, the Ln(III)
      coordination environments in the TBA(5)H(2)[(H(2)O)(n)Ln(alpha-1-P(2)W(17)O(61))]
      solid salts, including the extent of Ln hydration (n) upon their dissolution in
      acetonitrile, were determined through use of EXAFS, which demonstrates a
      structural uniformity among the salts and their acetonitrile solutions, wherein
      the average Ln-O interatomic distances and O coordination numbers reveal
      variations that are consistent with the effects of the lanthanoid contraction.
      The side-by-side comparison of the solid and solution data provides evidence that
      is consistent with a partial solvent (H(2)O-CH(3)CN) exchange upon dissolution in
      MeCN. Details of the Ln(III) coordination chemistry, wherein the decrease in the
      ionic radius from the large, light Nd(III) to the small, heavy Yb(III), are
      presented in the context of known structural and physical phenomena of
      acetonitrile solvates, aqua ions, and the corresponding water-soluble
      K(7)[(H(2)O)(4)Eu(alpha-1-P(2)W(17)O(61))] complex.

PMID- 20672168
TI  - A new rhodamine-based chemosensor for Cu2+ and the study of its behaviour in
      living cells.
AB  - A new rhodamine-based chemosensor (L1) was synthesized, and it exhibits high
      sensitivity and selectivity for the copper cation over other commonly coexistent
      metal ions in aqueous solution. Upon the addition of Cu(2+), the spirolactam ring
      of L1 was opened and a 1 : 1 metal-ligand complex was formed. Fluorescent imaging
      of Cu(2+) in living cells is also successfully demonstrated.

PMID- 20672169
TI  - Coordination chemistry of new selective ethylene trimerisation ligand
      Ph2PN(iPr)P(Ph)NH(R) (R = iPr, Et) and tests in catalysis.
AB  - The synthesis of [Ph(2)PN((i)Pr)P(Ph)NH(R)] (R = (i)Pr, Et) (1, 2) is described
      and the structure of 2 has been determined by single-crystal X-ray analysis.
      Compound 1 readily reacts with chromium(0), nickel(0), nickel(II), palladium(II),
      platinum(II) and iron(II) complexes to give four-membered rings (3-10) via P,P'
      coordination. The molecular structures of [Cr(CO)(4){Ph(2)PN((i)Pr)P(Ph)NH(R)
      P,P'}] (R = (i)Pr, Et) (3, 4), [Cr(CO)(3)(NCCH(3)){Ph(2)PN((i)Pr)P(Ph)NH((i)Pr)
      P,P'}] (5), [Ni{Ph(2)PN((i)Pr)P(Ph)NH((i)Pr)-P,P'}(2)] (6), cis
      [MX(2){Ph(2)PN((i)Pr)P(Ph)NH((i)Pr)-P,P'}] (M = Ni, Pd, Pt; X = Cl or Br) (7, 8,
      9) and trans-[Fe(NCCH(3))(2){Ph(2)PN((i)Pr)P(Ph)NH((i)Pr)-P,P'}(2)](BF(4))(2)
      (10) have been determined by X-ray diffraction. In the solid state, these
      complexes show tight phosphine bite angles in the range 67.89(2) degrees to
      74.97(4) degrees and the central nitrogen atom adopts an almost planar (sp(2))
      geometry. Complexes 3, 5, 6, 7 and 10 are tested for their catalytic activity in
      ethylene oligomerisation. Additionally, complex 10 is tested in hydrogenation of
      olefins.

PMID- 20672170
TI  - Photoelectrochemical behaviour of anatase nanoporous films: effect of the
      nanoparticle organization.
AB  - The photoelectrochemical behaviour of anatase thin films with different
      nanoarchitectures and the same active surface area (or thickness) has been
      studied in acidic media in the absence and in the presence of formic acid. The
      electrodes were composed of either wire-like nanocrystal aggregates or commercial
      TiO(2) nanoparticles. Cyclic voltammetry in the dark reveals a larger trap
      concentration in the band gap for the nanoparticulate (NP) electrodes, which can
      be ascribed to a larger number of intergrain boundaries. Also under illumination,
      the behaviour for both types of anatase structures significantly differs: water
      photooxidation arises at more negative potentials for the nanocolumnar (NC)
      electrodes. In the presence of an efficient hole acceptor such as HCOOH,
      significantly larger photocurrents were noted for the NC films as compared with
      those for the NP electrodes, with the photocurrent onset also shifted towards
      more positive potentials for the latter. These results point to a diminished
      electron recombination, which can be related with a smaller concentration of
      intergrain boundaries, together with a more efficient HCOOH hole transfer for the
      wire-like nanocrystal aggregate architecture. In addition, the oxygen reduction
      reaction is also favoured in the case of NC electrodes.

PMID- 20672171
TI  - Fluorescent proteins as light-inducible photochemical partners.
AB  - Green Fluorescent Protein (GFP) and other related fluorescent proteins are
      generally used as genetically encoded, chemically inert labels in vivo. This
      review focuses on the emerging application of fluorescent proteins as light
      inducible intracellular photochemical partners. The first example of a chemically
      active GFP-like protein was the phototoxic red fluorescent protein KillerRed,
      which can be used for precise light-induced killing of cells, protein
      inactivation, and studying reactive oxygen species signaling in different
      cellular compartments. Moreover, recent studies revealed that various GFPs can
      act as light-induced electron donors in photochemical reactions with biologically
      relevant electron acceptors. These findings have important implications for
      practical uses of fluorescent proteins as well as for our understanding of the
      evolution and biology of this protein family.

PMID- 20672172
TI  - Singlet oxygen photosensitisation by GFP mutants: oxygen accessibility to the
      chromophore.
AB  - Aiming at the rational development of genetically-encoded photosensitisers, the
      production of singlet oxygen has been assessed for a number of class-2 Green
      Fluorescent Protein (GFP) mutants by means of time-resolved near-infrared
      luminescence detection. The accessibility of molecular oxygen to the chromophore
      seems to play a major role in the ability of GFPs to photosensitise singlet
      oxygen and this can be modulated by introducing specific mutations such as
      replacement of His148 by a less bulky amino acid. GFPs are also good singlet
      oxygen quenchers, hence further developments in this area should also seek to
      eliminate those amino acids with the highest quenching ability, particularly
      those at the protein surface and in the vicinity of the chromophore.

PMID- 20672177
TI  - Probing peptide-nanomaterial interactions.
AB  - Peptide enabled synthesis of nanomaterials offer the ability to control size
      distributions; morphologies; and provide a range of surface functionalities.
      Invariably, these qualities are determined by how well peptides are able to
      interact with nanomaterials via their primary amino acid sequence and/or
      secondary structure. At present, though, the effect of the primary and secondary
      peptide structure on peptide-nanomaterial interactions is not well understood and
      lacks precise characterization with regard to peptide binding interactions. This
      shortcoming is even further complicated due to the fact that each peptide
      nanomaterial interaction is unique for a given set of peptides and nanoparticles.
      As a result, the behavior of peptides in the presence of nanomaterials requires a
      separate study and individual consideration on a peptide per peptide basis.
      Because of this, the effectiveness of peptide-nanoparticle complexes is often
      "hit or miss" under experimental conditions and when challenged with large sets
      of potential nanoparticle-binding peptides. In the following tutorial review, we
      highlight relevant peptide-nanoparticle interactions, describe binding and
      structural data for these interactions, and provide a general description of
      appropriate biochemical and physical characterization techniques adopted from
      materials science, structural biology, and biochemistry to probe synthetically
      produced peptide-nanoparticle complexes.

PMID- 20672178
TI  - Regulation of the properties of superoxide dismutase from the dental pathogenic
      microorganism Streptococcus mutans by iron- and manganese-bound co-factor.
AB  - Streptococcus mutans, the main pathogen involved in the development of dental
      caries, is an aerotolerant microorganism. The bacterium lacks cytochromes and
      catalase, but possesses other antioxidant enzymes, such as superoxide dismutase
      (SmSOD). Previous researches suggested that SmSOD belongs to the 'cambialistic'
      group, functioning with Fe or Mn in the active site. A recombinant SmSOD (rSmSOD)
      with a His-tail has been produced and characterised. Studies on metal uptake and
      exchange proved that rSmSOD binds either Fe or Mn as a metal co-factor, even
      though with a consistent preference for Fe accommodation. The analysis of several
      enzyme samples with different values of the Mn/Fe ratio in the active site proved
      that the type of metal is crucial for the regulation of the activity of rSmSOD.
      Indeed, differently from the significant preference for Fe displayed by the
      enzyme in the binding reaction, its Mn-form was 71-fold more active compared to
      the Fe-form. The rSmSOD was endowed with a significant thermostability, its half
      inactivation occurring after 10 min exposure at 71 or 73 degrees C, depending on
      the bound metal. Moreover, the enthalpic and entropic contribution to the heat
      inactivation process of rSmSOD were strongly regulated by the Mn content of the
      enzyme. The effect of typical inhibitors/inactivators has been investigated.
      rSmSOD was inhibited by sodium azide, and its sensitivity increased in the
      presence of higher Mn levels. Concerning two physiological inactivators, the
      enzyme displayed a different behaviour, being quite resistant to hydrogen
      peroxide and significantly sensitive to sodium peroxynitrite. Furthermore, the Mn
      co-factor had an amplifying role in the regulation of this different sensitivity.
      These results confirm the cambialistic nature of SmSOD and prove that its
      properties are regulated by the different metal content. The adaptative response
      of S. mutans during its aerobic exposure in the oral cavity could involve a
      different metal uptake by SmSOD.

PMID- 20672179
TI  - Programmable diagnostic devices made from paper and tape.
AB  - This paper describes three-dimensional microfluidic paper-based analytical
      devices (3-D microPADs) that can be programmed (postfabrication) by the user to
      generate multiple patterns of flow through them. These devices are programmed by
      pressing single-use 'on' buttons, using a stylus or a ballpoint pen. Pressing a
      button closes a small space (gap) between two vertically aligned microfluidic
      channels, and allows fluids to wick from one channel to the other. These devices
      are simple to fabricate, and are made entirely out of paper and double-sided
      adhesive tape. Programmable devices expand the capabilities of microPADs and
      provide a simple method for controlling the movement of fluids in paper-based
      channels. They are the conceptual equivalent of field-programmable gate arrays
      (FPGAs) widely used in electronics.

PMID- 20672180
TI  - Using heterogeneous data sources in a systems biology approach to modeling the
      Sonic Hedgehog signaling pathway.
AB  - Experimental data from biological pathways come in many forms: qualitative or
      quantitative, static or dynamic. By combining a variety of these heterogeneous
      sources of data, we construct a mathematical model of a critical regulatory
      network in vertebrate development, the Sonic Hedgehog signaling pathway. The
      structure of our model is first constrained by several well-established pathway
      interactions. On top of this, we develop a hierarchical genetic algorithm that is
      capable of integrating different types of experimental data collected on the
      pathway's function, including qualitative as well as static and dynamic
      quantitative data, in order to estimate model parameters. The result is a
      dynamical model that fits the observed data and is robust to perturbations in its
      parameters. Since it is based on a canonical power-law representation of
      biochemical pathways whose parameters can be directly translated into physical
      interactions between network components, our model provides insight into the
      nature and strength of pathway interactions and suggests directions for future
      research.

PMID- 20672181
TI  - [Indirect hyperbilirubinemia of genetic origin: Case report of Crigler-Najjar
      syndrome type II].
AB  - Crigler Najjar syndrome type II is related to a defect of bilirubin conjugation
      due to partial deficiency of the enzyme uridine diphosphate-glucuronyl
      transferase. Usually has a benign course, unlike Crigler Najjar type I, where the
      enzyme deficiency is total and the affected patients usually die at early ages.
      We present the case of a teenager with indirect hyperbilirubinemia, seizures and
      cerebral palsy. A good clinical history with pedigree and appropriate functional
      tests allowed us to determine the definitive diagnosis. This is an autosomal
      recessive disorder, has a very low prevalence worldwide, and is a diagnostic
      challenge for physicians in general.

PMID- 20672182
TI  - [Phenotypic variability in 47, XXX patients: Clinical report of four new cases].
AB  - The 47, XXX karyotype has a frequency of 1 in 1000 female newborns. However, this
      karyotype is not usually suspected at birth or childhood. These patients are
      usually diagnosed during adulthood when they develop premature ovarian failure or
      infertility, because the early phenotype doesn t have any specific features. The
      study describes four cases and the clinical variability of the 47, XXX karyotype.

PMID- 20672183
TI  - [Ex utero intrapartum treatment - Management of neonatal congenital high airway
      obstruction syndrome: Case report].
AB  - In recent years, the ex utero intrapartum treatment (EXIT), that involves
      extrauterine fetal intubation prior to delivery, has become relevant for the
      reduction in morbidity and mortality of neonates affected by congenital high
      airway obstruction syndrome (CHAOS). CLINICAL CASE: We report the case of the
      mother of an unborn child at pregnancy week 22, who was diagnosed a congenital
      pulmonary malformation that precluded intrapartum fetal circulatory deficit and
      resulted in the conduction of an EXIT technique, with the aim of ensuring fetal
      blood gas exchange at the time of delivery. CONCLUSIONS: A timely practice of the
      EXIT technique resulted, by monitoring both maternal and fetal factors that might
      affect fetoplacental circulation, in the birth of a child whose immediate and
      long-term outcomes were successful allowing the child live a normal life.

PMID- 20672184
TI  - [Allergic contact dermatitis for temporary "black henna" tattoos].
AB  - Temporary 'black henna' tattoos, an increasingly popular body decoration in
      pediatric population, are associated with a growing incidence of adverse events.
      Black henna does not exist naturally, it is obtained from original henna after
      the addition of other compounds, among them paraphenilendiamine (PPD), which
      serves to darken the tattoo and allows greater precision to the design. PPD is
      known to be a strong sensitizer and increases the risk of allergic contact
      dermatitis. They may present as long lasting local reactions, and pigmentary
      sequels apart from problems with the future use of many products present in the
      daily life, as a result of sensitization by PPD. We report the case of an eleven
      year old girl with an allergic contact dermatitis to black henna tattoo with a
      positive patch test to PPD, in order to warn against these types of temporary
      tattoos.

PMID- 20672185
TI  - [Why research is good].

PMID- 20672186
TI  - [Overweight and obesity in schoolchildren from Brandsen and its relationship with
      socio-environmental characteristics of residence].
AB  - INTRODUCTION: Environmental factors play an important role in the etiology of
      overweight (S) and obesity (O), constituting the "obesogenic environment". The
      objectives of the present study are: a) to estimate overweight and obesity
      prevalences in 3 to 14 years-old schoolchildren from Brandsen (Provincia de
      Buenos Aires), and b) to analyze the probability of occurrence of overweight and
      obesity in relation to the socioenvironmental conditions of resident. POPULATION
      AND METHODS: Weight and height were measured in 989 boys and girls aged 3 to 14
      years. S and O were estimated following the criteria suggested by the
      International Obesity Task Force. The prevalences of S and O were compared
      between genders and ages. The socio- environmental information was gathered
      according to surveys and processed by Categorical Principal Components Analysis
      (catPCA). Generalized Linear Model (link logit) against the variables S and O was
      employed. RESULTS: S was found in 15,8% of schoolchildren and O in 7,2%. None
      significative statistics differences between both genders and ages, were found.
      The first axis of the catPCA discriminated the cases that presented better socio
      environmental conditions with positive values and those with more unfavorable
      conditions with negatives values. Higher probability of obese children was
      associated with better socio-environmental conditions (higher educational level
      of parents, higher income and better access to public services), and higher
      probability of overweight children was associated with less favored environments.
      CONCLUSIONS: The schoolchildren population of Brandsen presents high overweight
      and obesity prevalences. The chance of presenting overweight is higher in
      children from households with adverse socio-environmental conditions. On the
      contrary, obese children are to be more found in households which have more
      favorable socio-environmental conditions.

PMID- 20672187
TI  - [Epidemiology of adverse events in the neonatal unit of a regional public
      hospital in Argentina].
AB  - Patient safety is one of the critical dimensions of quality of care. OBJECTIVE:
      To describe the epidemiology of adverse event (AE) in the neonatal unit of the
      Hospital Penna in Bahia Blanca, in 2006. METHODOLOGY: Cross-sectional study based
      on a two-stage-chart-review methodology. 1st stage: screening through indicators
      that allow the identification of hospitalizations with higher risk of AE; 2nd
      stage: AE confirmation (assessment of the existence, type, category,
      preventability and consequences of AE). RESULTS: 484 charts were included.
      Frequency of AE: 146 in 82 hospitalizations (16.9%) and an average of 3 out of 10
      hospitalizations. The most frequent AE were: nosocomial infections; catheter-use
      related events and extubations. The probability of AE was inversely associated
      with weight at birth and gestational age and directly related to length of stay
      (the longer the stay, the higher the probability). It was also positively
      associated with admission to the intensive care unit. CONCLUSION: The neonatal
      population, especially premature newborns, constitutes a group of high
      vulnerability to present AE. Most of these events are potentially preventable,
      which highlights the need of implementing effective interventions oriented to
      improve patient safety and quality of care.

PMID- 20672188
TI  - [Community-acquired Staphylococcus aureus bacteremia: 17 years of experience in
      Argentine children].
AB  - BACKGROUND: Community-acquired methicillin-resistant Staphylococcus aureus
      (CAMRSa) emerged in recent years. Few studies analyzed the impact of these
      infections in bacteremias (B). OBJECTIVES: To analyze clinical, epidemiological,
      microbiological and outcome of CASa B between two periods (Period I: 1993-2004,
      and Period II: 2004-2007). MATERIAL AND METHODS: Retrospective, observational and
      comparative study. All children older than 1 month of age and CASaB were
      included. RESULTS: During the study period 647 SaB were diagnosed (Period I: 499
      and Period II: 148). Of them, 140 (28%) and 49 (33%) were CSaB, respectively. The
      median age of patients was 5.9 and 4.8 years, respectively (p= NS). Clinical foci
      of infection and septic shock were more frequent in the period I (78% vs. 47%)
      and (5% vs. 16%) (p <0.05), respectively. Skin infection and septic shock were
      similar in both periods (78% vs. 67% and 5% vs. 8%; p= NS). Four CAMRSa B (3%)
      were diagnosed during the first period. One predisposing factor was identified in
      all cases. Inversely, 23 cases (47%) were diagnosed during the Period II (p
      <0.05). Resistance rates to clindamycin and gentamicin were more high during the
      second period (10% vs. 2% and 20% vs. 3%, respectively) (p <0.05). Patients in
      the second period had longer antibiotic treatment (X 16.6 vs. 10.1 days) and more
      frequent inappropriate treatment at admission (53% vs. 5%) (p <0.05). Hospital
      stay time was longer during de first period (19.2 vs. 12.2 days) (p <0.05). The
      mortality rate was higher in the first period (13% vs. 4%) (p= NS). CONCLUSION: A
      significant increase of CAMRSa B were detected in recent years. It is necessary
      to evaluate the empirical treatment of severe community infections in children in
      our country.

PMID- 20672189
TI  - [Knowledge, attitudes, and practices of Argentine pediatricians regarding second
      hand smoke exposure in children].
AB  - INTRODUCTION: Passive smoking is a main public health problem in Argentina. It is
      estimated that about 55% of children live with a smoker at home. Several reports
      show that when parents and providers refrain from smoking at home and in the car,
      environmental tobacco exposure (ETS) and its health consequences decrease.
      OBJECTIVE: To assess pediatricians' knowledge, beliefs and practices regarding
      passive smoking and its prevention. METHODOLOGY: We surveyed a national sample of
      pediatricians, who participated in the National Pediatric Continuous Education
      Program (PRONAP) of the Argentine Pediatric Society, via e-mail. RESULTS:
      Overall, 74% of the pediatricians that answered the questionnaire said that they
      always asked about ETS exposure during the pediatric visit, 50% writes that on
      the children's chart, 93% advises parents not to smoke at home, 64% motivates
      parents to quit smoking and 49% provides information materials about the topic.
      Overall, their knowledge about the diseases most associated with ETS is
      appropriate. Almost all pediatricians believe the topic is of public health
      importance and important for children's health. CONCLUSIONS: The results of this
      survey show it is important to improve the training provided to pediatricians and
      to standardize the discussion and the treatment of ETS during the pediatric
      visit.

PMID- 20672190
TI  - [Access to a III level neonatal intensive care unit in Argentina].
AB  - INTRODUCTION: In Argentina information does not exist about how many newborns
      (NB) who need to be hospitalized in a third level neonatal intensive care unit
      (NICU) actually accede, not even about the evolution of those who cannot accede.
      OBJECTIVE: To analize the characteristics of NB that required to be hospitalized
      in a NICU and the evolution of those who do not accede. METHODS: Longitudinal,
      prospective and observational study. There were included NB that required
      hospitalization in the NICU of the Hospital Garrahan during eleven months. Every
      request was registered and phone calls were made to know the evolution of
      rejected NB. The accessibility was analyzed by bivariated and multivariated
      tests. RESULTS: 1197 NB were included in the study; 75% with severe clinical
      condition, being of higher frequency the cardiac, respiratory and surgical
      pathologies; 637 NB (53%) were accepted. The NB from other provinces (OR 2, IC95%
      1.4-2.8), retinophaty of the premature (OR 40, IC95% 14-85) and surgical disease
      (OR 1.99, IC95% 1.4-2.7) were independent factors that increased the
      possibilities to access; it decreased during the winter (OR 0.56, IC95% 0.40
      0.77); 56 NB died; 47 could not have access to a third level NICU in spite of
      presenting pathologies sensitive of treatment. CONCLUSION: This information shows
      the fact that is of high importance to define regional strategies that allow the
      efficient administration of existing health resources and the opportune access of
      seriously ill NB patients to reference centers.

PMID- 20672191
TI  - [Genetics of development and behaviour].
AB  - Quantitative genetics can make a significant contribution to disentangle the
      relative influence of genetics and environment on human development and its
      disorders. Estimates of Pearson s correlation coefficients between siblings, mono
      and dizogotic twins reared together or apart, allows the calculation of
      heredability, that is, the contribution of genetics to the variance of a given
      trait. In the case of many aspects of intellectual development, heredability is
      around 50%. The rests is attributable to the influence of environment. The
      influence of genetics on development should be considered as a trend, a risk,
      rather than a programmed fate.

PMID- 20672192
TI  - [Portal hypertension in pediatrics: II: Hemorrhagic complications].
AB  - Bleeding from esophageal varices is the most severe complication of portal
      hypertension, and should be managed in specially trained centers. Vasoactive
      drugs, mainly octreotide, plus endoscopic treatment are able to control bleeding
      in 90% of the cases. Rescue treatments like TIPS and surgery should be
      immediately available for those who do not stop bleeding or have varices
      difficult to manage.

PMID- 20672193
TI  - [Transgenic animals: uses and limitations in the 21st century medicine].
AB  - One of the most important advances in biotechnology during the last decades was
      the development of transgenic animals. In this article, I discuss why transgenic
      animals are excellent models to analyze gen function and regulation, and to look
      for new therapeutic strategies for human diseases. Moreover, their use as
      bioreactors to produce pharmaceutical products for the treatment of human
      diseases, and the possibility of generating transgenic pigs as an alternative
      source of organ donors for humans is also discussed.

PMID- 20672194
TI  - [Early weaning and adult behavioral disorders in an animal model].
AB  - Early weaning (EW) has proven to be a factor that decreases the animal's organic
      resistance against adverse conditions. Climbing in the forced swimming test (FST)
      is the active behavior that expresses the will of the rat to escape the stressful
      situation. A possible association between these two stress factors (EW and FST)
      has not yet been reported as a plausible model for the study of stress and
      depression. Under the working hypothesis that EW has possible adult behavioral
      correlates when associated with the FST, our objective was to analyze the levels
      of alteration in the active behaviors among groups. 20 Wistar rats (4 month old),
      were divided into two groups, the early weaned group (G1) and a control group
      (G2). The unit of analysis (tip), was defined as the number of intended escapes
      the animal performs in five minutes. We have found the differences stated by our
      hypothesis, comparing the frequency of scale or escape (tips), from a group with
      EW to a control group (15.8 +/- 4.15 vs. 21.4 +/- 4.14, p< 0.05). In turn, we
      found that, among females, the difference was significantly wider. The present
      study could elucidate under experimental conditions the effect that in adult
      behavior induces an alteration in the more primary bonds.

PMID- 20672195
TI  - [Nephrourologic pathology in girls with Turner syndrome].
AB  - Nephrourologic malformations in Turner syndrome are frequent, its diagnosis and
      follow-up is important in order to diminish the morbidity of this disease. The
      aim of this retrospective study was to analyze the nephrourologic pathology in 72
      girls with Turner syndrome followed between 1989 and 2008 at Garrahan Hospital.
      The prevalence of nephrourologic involvement was 33% (24 patients). The most
      frequent findings were urinary system malformations, isolated (10 pacientes, 42%)
      or associated with renal malformations (9 patients, 37%); 5 patients (21%) had
      only renal malformations. Fifty percent of patients developed complications (8
      urinary tract infection, 2 proteinuria and 2 arterial hypertension); however,
      none progressed to chronic renal failure. The prevalence of nephrourologic
      involvement was 33% and a half of these girls developed complications, our
      findings show the need of routine nephrological follow-up of girls with Turner
      syndrome and nephrourologic malformations.

PMID- 20672196
TI  - [Infantile cortical hyperostosis: Caffey's disease].

PMID- 20672198
TI  - [Menstrual cycle disorders in adolescence].
AB  - The high prevalence of menstrual disorders during the first years after menarche
      is well recognized. This is usually a cause of concern for parents and patients,
      and a common reason for visiting the pediatrician. The immaturity of the
      hypothalamic-pituitary-ovarian axis is the major cause of these disorders, but
      there are also some general organic or emotional conditions that may alter the
      menstrual cycle, which is a sensitive indicator of health. Physiology of the
      menstrual cycle, its alterations, etiology, assessment, diagnosis and treatment
      are reviewed in this article.

PMID- 20672200
TI  - Adsorption from saliva to silica and hydroxyapatite surfaces and elution of
      salivary films by SDS and delmopinol.
AB  - The adsorption of proteins from human whole saliva (HWS) onto silica and
      hydroxyapatite surfaces (HA) was followed by quartz crystal microbalance with
      dissipation (QCM-D) and ellipsometry. The influence of different surface
      properties and adsorption media (water and PBS) on the adsorption from saliva was
      studied. The viscoelastic properties of the salivary films formed on the solid
      surfaces were estimated by the use of the Voigt-based viscoelastic film model.
      Furthermore, the efficiency of SDS and delmopinol to elute the adsorbed salivary
      film from the surfaces was investigated at different surfactant concentrations. A
      biphasic kinetic regime for the adsorption from saliva on the silica and HA
      surfaces was observed, indicating the formation of a rigidly coupled first layer
      corresponding to an initial adsorption of small proteins and a more loosely bound
      second layer. The results further showed a higher adsorption from HWS onto the HA
      surfaces compared to the silica surfaces in both adsorption media (PBS and
      water). The adsorption in PBS led to higher adsorbed amounts on both surfaces as
      compared to water. SDS was found to be more efficient in removing the salivary
      film from both surfaces than delmopinol. The salivary film was found to be less
      tightly bound onto the silica surfaces since more of the salivary film could be
      removed with both SDS and delmopinol compared to that from the HA surface. When
      adsorption took place from PBS the salivary layer formed at both surfaces seemed
      to have a similar structure, with a high energy dissipation implying that a
      softer salivary layer is built up in PBS as opposed to that in water.
      Furthermore, the salivary layers adsorbed from water solutions onto the HA were
      found to be softer than those on silica.

PMID- 20672201
TI  - Do New Zealand's immigrants have a mortality advantage? Evidence from the New
      Zealand Census-Mortality Study.
AB  - OBJECTIVE: To examine all-cause mortality differentials among New Zealand's (NZ)
      immigrant population. Unlike other studies that use the total non-migrant
      population as the reference group, we use NZ-born populations of the same ethnic
      group for comparison purposes. Our study intends to answer two questions: first,
      do immigrants have a mortality advantage relative to their NZ-born counterparts
      of the same ethnicity? Second, does an immigrant mortality advantage, if one
      exists, decline as duration of residence increases? DESIGN: Data from the New
      Zealand Census-Mortality Study from 1996-1999 and 2001-2004 were used. The main
      variable of interest, years of residence in NZ, was classified as living in NZ
      for less than 5, 5-9, 10-19, 20-34, 35 or more years, and born in NZ. Three main
      ethnic groups were examined, such as Asian, Pacific, and European/Other.
      Mortality rates for subgroups within these broad ethnic groups were not
      calculated. Negative binomial models controlled for socioeconomic and demographic
      factors to assess the independent effect of duration of residence on mortality.
      RESULTS: European/Other and Asian immigrants have a mortality advantage relative
      to their NZ-born counterparts, which declines as length of residence increases.
      Within strata of duration of residence, there are few differences between
      European/Other and Asian mortality. Pacific immigrants showed no statistically
      significant mortality advantage relative to the NZ-born Pacific people, and had
      higher mortality rates than Europeans/Others or Asians regardless of duration in
      NZ. CONCLUSION: Findings from our study are consistent with international
      literature. Both the healthy migrant effect and acculturation may be responsible
      for the protective mortality effect among Asians and Europeans/Others that erodes
      over time. However, our results for the Pacific population suggest some migrant
      groups come to the host country with a health disadvantage and with no apparent
      healthy migrant effect.

PMID- 20672202
TI  - Religious and ethnic differences in health: evidence from the Health Surveys for
      England 1999 and 2004.
AB  - OBJECTIVES: To examine the role of religion in the patterning of health
      inequities, and how this is related to ethnicity and socioeconomic status.
      DESIGN: Multivariate analyses using nationally representative data on self
      assessed fair or poor health, longstanding limiting illness, diagnosed diabetes,
      diagnosed hypertension, waist-hip ratio, body mass index, current tobacco use and
      participating in no regular physical activity from 14,924 Christians, 4337
      Muslims, 656 Sikhs, 1197 Hindus and 2682 people reporting not identifying with
      any religion with different ethnic backgrounds, who were interviewed as part of
      the Health Survey for England in either 1999 or 2004, adjusted for age, gender
      and socioeconomic status and periodicity. RESULTS: Odds ratios for general
      health, hypertension, diabetes, waist-hip ratio, tobacco use and physical
      activity speak to the importance of ethnicity in the patterning of health
      inequalities. But there is also evidence of an important, independent role for
      religion, with risks for the different health indicators varying between people
      with the same ethnic, but different religious, identifications. Adjusting for
      socioeconomic status attenuated the ethnic/religious patterning of, particularly,
      self-assessed health, longstanding activity-limiting illness, waist-hip ratio,
      body mass index and tobacco use. CONCLUSIONS: This evidence enables greater
      understanding of the complexities of the relationship between ethnicity, religion
      and health, recognising the need to understand the heterogeneity underlying both
      ethnic and religious group membership and the processes producing the structural
      disadvantage facing certain religious and ethnic groups in the mediation of the
      relationship between health and ethnicity/religion.

PMID- 20672203
TI  - Use of retailer fidelity card schemes in the assessment of food additive intake:
      Sunset Yellow a case study.
AB  - The feasibility of using a retailer fidelity card scheme to estimate food
      additive intake was investigated using the Swiss retailer MIGROS's Cumulus Card
      and the example of the food colour Sunset Yellow (E 110). Information held within
      the card scheme was used to identify a sample of households purchasing foods
      containing Sunset Yellow over a 15 day period. A sample of 1204 households was
      selected for interview, of which 830 households were retained in the study
      following interview. Interviews were conducted to establish household structure,
      patterns of consumption by different individuals within the household, and the
      proportion of foods containing Sunset Yellow habitually purchased at the retailer
      and/or consumed outside the home. Information provided by the retailer on levels
      of Sunset Yellow in the foods was combined with the information obtained at
      interview to calculate the per-capita intake of Sunset Yellow by members of
      participating households. More than 99% of consumers (n = 1902) of foods
      containing Sunset Yellow were estimated to consume less than 1 mg Sunset Yellow
      kg(-1) body weight day(-1). The method proved to be a simple and resource
      efficient approach to estimate food additive intake on the basis of actual
      consumer behaviour and thus reports results more closely related to the actual
      consumption of foods by individuals.

PMID- 20672204
TI  - Controlled release of alpha-tocopherol, quercetin, and their cyclodextrin
      inclusion complexes from linear low-density polyethylene (LLDPE) films into a
      coconut oil model food system.
AB  - Polymer additive migration into a food product is dependent upon numerous factors
      including the original concentration of the additive in the polymer, its
      solubility in the food, its diffusion coefficient in the polymer, its partition
      coefficient between the polymer and food, temperature, and time. The limited
      solubility of quercetin in linear low-density polyethylene (LLDPE) did not allow
      release from the film due to phase segregation of the quercetin in the bulk
      polymer. Increasing the molecular weight of alpha-tocopherol by beta-cyclodextrin
      inclusion complexation can greatly reduce its diffusion coefficient in LLDPE.
      Ziegler-Natta and metallocene LLDPE contain different crystalline structure
      morphologies and diffusion path networking arrangements that allow for
      differences in additive release rates. Effective controlled-release packaging
      should combine beta-cyclodextrin complexation of additives and polymer morphology
      control to target delivery of an optimal antioxidant concentration to achieve
      prolonged activity, resulting in extended shelf life foods.

PMID- 20672205
TI  - Nitrogen retention in the Szczecin Lagoon, Baltic Sea.
AB  - Nitrogen (N) retention and transformation in the Szczecin Lagoon, southern Baltic
      Sea, were studied by means of budget calculations and stable isotope data of
      dissolved and particulate matter. Two stations, one located at the main outlet of
      the lagoon (Swina Strait) and the other 100 km to the south, on the Oder River
      (Widuchowa), were sampled biweekly over the years 2000-2002. The Oder River is
      one of the five largest rivers draining into the Baltic Sea and the largest one
      discharging its waters into the western Baltic. According to our data, the Oder
      River carried approximately 60 kt y(-1) total N, of which 7 kt y(-1) (<12 %) are
      particulate organic nitrogen and 46 kt y(-1) (77 %) dissolved inorganic nitrogen.
      Seasonal patterns of particulate nitrogen and nitrate concentrations were similar
      at Widuchowa and Swina Strait station, but nitrate concentrations in the Swina
      Strait were much lower, pointing not only to the dilution effect but also to
      considerable nutrient removal capacity (especially of nitrate) in the lagoon. The
      loss of nitrate suggests that denitrification is the major N-removal process,
      whereas primary production was only a minor contributor, due to the very low
      particle load. Combining budget calculations with stable isotope measurements
      reveal unique information about nitrogen turnover processes in the lagoon.

PMID- 20672206
TI  - Educator sexual abuse: introduction and overview.

PMID- 20672207
TI  - Teacher sexual misconduct: grooming patterns and female offenders.
AB  - Educator sexual misconduct has received increasing attention over the past
      decade. The attention has exposed a number of concerning issues, including a lack
      of formal research in the area and difficulties in recognizing and prosecuting
      cases. Public responses to high profile cases of sexual misconduct involving
      female teachers suggest that gender-biased views on sex offenders remain
      prominent in society. This article will review the literature on female teacher
      sexual misconduct in addition to what is known about grooming patterns and
      warning signs. Finally, current dilemmas in resolving cases of educator sexual
      misconduct will be discussed, and basic prevention strategies will be
      recommended.

PMID- 20672208
TI  - Educator sexual abuse: two case reports.
AB  - Sexual abuse by educators has become an increasingly noted type of sexual abuse,
      especially among adolescents, for two reasons. First, there is a potential for
      these cases to be silent and prolonged and second, when disclosed, the forensic
      implications usually include both criminal and/or civil sanctions. For forensic
      case evaluations, developmental traumatology, or the intersection of the
      traumatic event(s) at a particular age of the student, is often the evaluating
      framework. We report on two forensic cases of a female student and a male student
      to emphasize the dynamics of adolescent sexual victimization, its impact on
      adolescent development, and evidence-based practice for symptom identification
      and treatment.

PMID- 20672209
TI  - A description of sexual offending committed by Canadian teachers.
AB  - The aim of this investigation was to describe teachers who sexually offend
      against youth and the circumstances related to these offenses. Archival Violent
      Crime Linkage Analysis System reports were obtained from the Royal Canadian
      Mounted Police, and demographic and criminal characteristics for the offender, as
      well as information about the victim and offense, were selected for analyses. A
      descriptive approach was used to analyze the qualitative reports for a group of
      113 Canadian sexual offenders between 1995 and 2002. The results provide a
      description of adult male teachers who offended within their position of trust as
      well as offense and victim characteristics.

PMID- 20672210
TI  - Effect of student vulnerability on perceptions of teacher-student sexual
      involvement.
AB  - This study explored whether the vulnerability of an adolescent student affected
      perceptions of teacher sexual misconduct. Respondents (150 male and 150 female
      undergraduates) read scenarios depicting teacher sexual misconduct varied by
      respondent gender, gender dyad (male teacher-female student and female teacher
      male student), and three levels of student vulnerability. The vulnerability of
      the student was found to have little impact on perceptions. On most variables,
      interactions emerged between respondent gender and gender dyad. Specifically,
      male respondents viewed the female teacher-male student dyad less negatively than
      the male teacher-female student dyad. Female respondents generally did not make
      distinctions based on gender dyad.

PMID- 20672211
TI  - An exploratory analysis of executive functioning for female sexual offenders: a
      comparison of characteristics across offense typologies.
AB  - This study examined the association between female sexual offending behavioral
      patterns, as delineated by Sandler and Freeman's (2007) typologies, and executive
      functioning. The sample included all referrals for sexual offender assessments
      within a women's maximum/medium security prison between January 2009 and October
      2009. Each subject was administered the Stroop (Golden & Freshwater, 2002) and
      Trail Making Test (Reitan, 2004) and were assigned to a typological category.
      Nonparametric analyses were conducted to determine if there was an association
      between typology and performance on neuropsychological tests. Results yielded no
      significant associations between test scores and typological category. Subjects
      displayed average capacities for a subset of executive functions, suggesting that
      the mechanisms for sexually offending behavior in females may differ from males.

PMID- 20672212
TI  - Exploring the overlap in male juvenile sexual offending and general delinquency:
      trauma, alcohol use, and masculine beliefs.
AB  - Despite Burton and Meezan's (2004) finding that sexually aggressive youth are
      three to four times more likely to recidivate nonsexually than sexually, there is
      little to no research to date that explores this overlap in criminality. With a
      sample of 290 male sexually violent adjudicated and incarcerated youth, this
      study was able to successfully predict those who are exclusively sexually violent
      from those who are both nonsexually and sexually violent with each of the
      following factors: childhood trauma, masculine beliefs, and alcohol use. While
      alcohol use accounted for the greatest variance between the groups, masculine
      beliefs offered the greatest basis for the discussion and future projects for the
      authors of the study. Treatment and research implications are offered.

PMID- 20672213
TI  - Assessing sexual abuse/attack histories with bariatric surgery patients.
AB  - This study assessed sexual abuse/attack histories in 573 [corrected] bariatric
      surgery patients using the PsyBari. The prevalence rates found were lower (15.5%,
      19.3% of women, 5.2% of men) than other studies that used bariatric surgery
      patients but consistent with studies that used nonbariatric obese subjects.
      Furthermore, bariatric surgery patients who disclosed sexual abuse/attack were
      more likely to disclose physical abuse, psychological problems, psychological
      treatment, psychiatric medication, and psychiatric hospitalization. Among
      bariatric surgery patients who disclosed sexual abuse/attack, females were more
      likely to disclose suicidal ideation. A logistic regression found that for
      females, physical abuse and suicidal ideation reliably predicted abuse/attack
      status. For males, psychological problems, psychiatric medications,
      hospitalization, and suicidal ideation, reliably predicted abuse/attack status.

PMID- 20672214
TI  - A model of adolescents' seeking of sexual content in their media choices.
AB  - This article reports on the extent to which adolescents report actively seeking
      sexual content in media, identifies from which media they report seeking,
      estimates the association between seeking sexual information and romantic and
      sexual behavior, and shows that active seeking of sexual content in media sources
      is explained by an intention to seek such content using the Integrative Model of
      Behavioral Prediction, a reasoned action approach. The data are a national sample
      of 810 adolescents aged 13 to 18 years. Results show that 50% of adolescents
      reported actively seeking sexual content in their media choices, which included
      movies, television, music, Internet pornography sites, and magazines. Males
      sought sex content more than females, and gender differences were greatest for
      seeking from Internet pornography sites, movies, and television. Path analysis
      demonstrate that seeking sexual content is well-predicted by intentions to seek,
      and intentions are primarily driven by perceived normative pressure to seek
      sexual content.

PMID- 20672215
TI  - Positioning the booty-call relationship on the spectrum of relationships: sexual
      but more emotional than one-night stands.
AB  - Most research on human sexuality has focused on long-term pairbonds and one-night
      stands. However, growing evidence suggests there are relationships that do not
      fit cleanly into either of those categories. One of these relationships is a
      "booty-call relationship." The purpose of this study was to describe the sexual
      and emotional nature of booty-call relationships by (a) examining the types of
      emotional and sexual acts involved in booty-call relationships and (b) comparing
      the frequency of those acts in booty-call relationships to one-night stands and
      serious long-term relationships. In addition, the manner in which sociosexuality
      is associated with the commission of these acts was also examined. Demonstrative
      of booty-call relationships' sexual nature was individuals' tendency to leave
      after sex and infrequent handholding. In contrast, the romantic nature of booty
      call relationships was demonstrated through the frequency of acts like kissing.
      The results suggest the booty-call relationship is a distinct type of
      relationship situated between one-night stands and serious romantic
      relationships.

PMID- 20672216
TI  - An evaluation of the relationship between body image and sexual avoidance.
AB  - This study examined the relationship between body image and sexual avoidance. Of
      particular interest was whether this relationship was mediated by other
      variables. Participants were 362 undergraduate students who responded to a
      battery of questionnaires pertaining to three aspects of body image, sexually
      avoidant behavior, and three mediator variables, which included sexual esteem,
      sexual satisfaction, and sexual desire. Consistent with previous studies, a
      relationship between body image and sexual avoidance was found, indicating that
      those with a more negative body image displayed a greater tendency to avoid
      sexual activity. Furthermore, sexual esteem, sexual satisfaction, and sexual
      desire appeared to mediate this relationship. Implications of these results
      suggest that these mediator variables are important in the relationship between
      body image and sexual avoidance, and may be useful targets for those seeking
      treatment for sexual avoidance issues. Limitations of the study and avenues for
      future research are discussed.

PMID- 20672217
TI  - The gift of agency: sexual exchange scripts among Nigerian youth.
AB  - This article examines the practice of directly exchanging goods for sexual
      intercourse using data from 36 focus-group discussions with youth living in rural
      southern Nigeria. Conceptualizing this practice as a sexual script, the authors
      conduct a deductive thematic analysis framed by the broader context in which
      sexual exchange occurs. Combining scripting theory with an analysis of the form
      of the payment, it was found that the cultural script of exchange supports girls'
      agency. However, at the interpersonal level of practice, this script often loses
      out in conflict with the cultural scripting of male control. The shape of this
      practice is influenced by intrapsychic scripts (e.g., sexual violence is an
      option), interpersonal resources (e.g., family money), and cultural scripts
      (e.g., stuff and status bring friends). In the final analysis, sexual exchange is
      found to be a script that both enables and restricts agency. It is a power niche
      for those with limited social and economic power, enabling them to seek and
      access material goods, social status, and sexual experience. It is also a means
      of coercing unwanted sex via peer and parental pressure, poverty, and a context
      of gender inequality. Implications for HIV prevention are discussed.

PMID- 20672218
TI  - Gender and age inequalities in regular sports participation: a cross-national
      study of 25 European countries.
AB  - This article provides a unique opportunity to compare gender inequalities in
      sports participation across Europe, and the extent to which this varies by age
      using large, cross-sections of the population. The Eurobarometer Survey 62.0
      (carried out in 2004 at the request of the European Commission and covering the
      adult population of 25 European member states, N = 23,909) was used to analyse
      differences in regular sports participation by gender and by age in the different
      countries. For the majority of countries, the occurrence of regular sporting
      activity was less than 40%. Additionally, binary logistic regression analyses
      identified significant gender differences in sports participation in 12
      countries. In Belgium, France, Greece, Latvia, Lithuania, Slovakia, Spain, and
      the UK, men were more likely to report being regularly active in sports than
      women, whereas in Denmark, Finland, Sweden, and the Netherlands the opposite was
      true. Moreover, the extent to which these gender inequalities differ by age
      varies considerably across countries. The results imply that: (i) in some
      European countries more efforts must be undertaken to promote the original goals
      of the Sport for All Charter, and (ii) to achieve more female participation in
      sports will require different policy responses in the diverse European member
      states.

PMID- 20672219
TI  - Assessing the fairness of the golf handicapping system in the UK.
AB  - In this paper, I examine the properties of the handicapping system in the UK.
      Using a generalized ordered logistic regression model of hole by hole scores of
      individuals, simulation was employed to calculate the probability of winning for
      an individual in stroke play and match play head to heads and also in tournament
      competitions with multiple entrants. The results suggest that the current
      handicapping system does not produce equal probabilities of players with
      different handicaps winning. Specifically, lower handicappers have a higher
      probability of winning in both stroke play and match play games. Having
      investigated the possibility of employing scaling factors in order to level these
      probabilities, I pose the question of the extent to which equal probabilities is
      in fact a desirable property of a handicapping system.

PMID- 20672220
TI  - Estimation of the energy loss at the blades in rowing: common assumptions
      revisited.
AB  - In rowing, power is inevitably lost as kinetic energy is imparted to the water
      during push-off with the blades. Power loss is estimated from reconstructed blade
      kinetics and kinematics. Traditionally, it is assumed that the oar is completely
      rigid and that force acts strictly perpendicular to the blade. The aim of the
      present study was to evaluate how reconstructed blade kinematics, kinetics, and
      average power loss are affected by these assumptions. A calibration experiment
      with instrumented oars and oarlocks was performed to establish relations between
      measured signals and oar deformation and blade force. Next, an on-water
      experiment was performed with a single female world-class rower rowing at
      constant racing pace in an instrumented scull. Blade kinematics, kinetics, and
      power loss under different assumptions (rigid versus deformable oars; absence or
      presence of a blade force component parallel to the oar) were reconstructed.
      Estimated power losses at the blades are 18% higher when parallel blade force is
      incorporated. Incorporating oar deformation affects reconstructed blade
      kinematics and instantaneous power loss, but has no effect on estimation of power
      losses at the blades. Assumptions on oar deformation and blade force direction
      have implications for the reconstructed blade kinetics and kinematics. Neglecting
      parallel blade forces leads to a substantial underestimation of power losses at
      the blades.

PMID- 20672221
TI  - Functional differences in the activity of the hamstring muscles with increasing
      running speed.
AB  - In this study, we examined hamstring muscle activation at different running
      speeds to help better understand the functional characteristics of each hamstring
      muscle. Eight healthy male track and field athletes (20.1 +/- 1.1 years)
      performed treadmill running at 50%, 75%, 85%, and 95% of their maximum velocity.
      Lower extremity kinematics of the hip and knee joint were calculated. The surface
      electromyographic activities of the biceps femoris and semitendinosus muscles
      were also recorded. Increasing the running speed from 85% to 95% significantly
      increased the activation of the hamstring muscles during the late swing phase,
      while lower extremity kinematics did not change significantly. During the middle
      swing phase, the activity of the semitendinosus muscle was significantly greater
      than that of the biceps femoris muscle at 75%, 85%, and 95% of running speed.
      Statistically significant differences in peak activation time were observed
      between the biceps femoris and semitendinosus during 95%max running (P < 0.05 for
      stance phase, P < 0.01 for late swing phase). Significant differences in the
      activation patterns between the biceps femoris and semitendinosus muscles were
      observed as running speed was increased, indicating that complex neuromuscular
      coordination patterns occurred during the running cycle at near maximum sprinting
      speeds.

PMID- 20672222
TI  - Action-intentional spatial bias in a patient with posterior cortical atrophy.
AB  - Patients without sensory neglect might demonstrate a spatial deviation when
      drawing. To better understand the mechanism of this deviation, we examined a 61
      year-old woman with probable posterior cortical atrophy (PCA) who on imaging
      showed right hemisphere atrophy and dysfunction. When drawing a clock she
      correctly made a circle, but when writing the numbers deviated to the left. A
      blindfolded midsagittal plane pointing test revealed that her leftward deviation
      was action-intentional rather than perceptual-attentional. This action
      intentional deviation was made manifest by altering visual feedback such as
      having her focus her attention on the clock numbers.

PMID- 20672223
TI  - The specificity of notation codes in apraxic agraphia: dissociation between
      Arabic and alphabetical scripts in a patient with severe ideomotor and
      visuoconstructional apraxia.
AB  - This article describes the case of a patient with corticobasal syndrome, who
      showed severe ideomotor and visuoconstructional apraxia along with handwriting
      difficulties more marked for letters and words than for digits and numbers. For
      alphabetical script, these difficulties were less marked when graphic motor
      patterns were activated with a model, whilst for digits IV's graphic productions
      were better in dictation. Moreover, IV's graphic production was negatively
      influenced by graphomotor complexity for letters but not for numbers. IV is the
      first reported case of a patient with severe limb apraxia, who also showed
      peripheral agraphia, with dissociation in alphabetical and numerical notation
      codes resulting from a specific deficit in the activation of graphomotor
      programs.

PMID- 20672224
TI  - Functional relations trump implied motion in recovery from extinction: evidence
      from the effects of animacy on extinction.
AB  - Patients with extinction show a characteristic impairment in the identification
      of objects when two items are presented simultaneously, typically reporting the
      ipsilesional item only. The effect is thought to be due to a spatial bias
      advantaging the ipsilesional item under conditions of competing concurrent
      stimulation. Action relations between objects can result in recovery from
      extinction as the object pair may be perceived as a single group rather than
      competing perceptual units. However, objects interacting together can also have
      implied motion. Here we test whether implied motion is necessary to generate
      recovery from extinction. We varied orthogonally whether animate and inanimate
      objects were paired together in positions related or unrelated to action. Implied
      motion was greater when an animate object was present than when both stimuli were
      inanimate. Despite this, recovery from extinction was greater when actions were
      shown between inanimate objects. We suggest that actions between inanimate
      objects are perceived more easily due to the surfaces of these stimuli being
      designed for functional goals (e.g., the flat surface of a hammer head is
      designed to hit the flattened head of a nail). Attention is sensitive to the fit
      between potential action and the functional properties of objects, and not just
      to implied motion between stimuli.

PMID- 20672225
TI  - [Liver, kidney and heart in obesity: three organs into the same boat (not to
      mention the fat)].

PMID- 20672226
TI  - [VDR and CaSR: from parathyroids to arteries].

PMID- 20672227
TI  - [25(OH)D (25-hydroxy vitamin D): a ''Cinderella'' in nephrology].

PMID- 20672228
TI  - [Cancer treatment-induced nephrotoxicity: BCR-Abl and VEGF inhibitors].

PMID- 20672229
TI  - [This cell will self-eat in 6 hours].

PMID- 20672230
TI  - [Mendelian randomization as an ''instrumental variable'' in observational
      studies].

PMID- 20672231
TI  - [The usefulness of protocol biopsies after kidney transplant: pros and cons].
AB  - Transplant centers carrying out protocol biopsies in kidney transplant recipients
      do so to make an early diagnosis of subclinical rejection or chronic transplant
      glomerulopathy. However, proof is still lacking to document that an early
      diagnosis of subclinical rejection is useful to improve long-term outcome.
      Protocol biopsies represent a classical controversy in renal transplantation and
      it is still not clear whether the benefits outweigh the risks. In this paper the
      authors will elucidate the pros and cons of protocol biopsies and identify issues
      where consensus is mandatory. Protocol biopsies need to be performed in the
      following clinical conditions: at the time of transplantation to obtain
      information about the transplanted kidney; in the case of prolonged delayed graft
      function; in patients at increased immunological risk; and in the case of
      clinical trials performed to assess the safety and efficacy of new
      immunosuppressive drugs.

PMID- 20672232
TI  - [From pharmacogenetics to pharmacogenomics: the start of a new era of
      personalized medicine in nephrology].
AB  - Recent evidence suggests that adverse drug reactions are a major cause of death
      and hospital admissions in Europe and the United States. Environmental/ non
      genetic as well as genetic factors are responsible for the great interpatient
      variability in drug metabolism and in the molecular interactions between drugs
      and therapeutic targets. By means of pharmacogenetic approaches, several genetic
      settings have been linked to the effects and toxicity of many agents used in
      clinical nephrology. However, these strategies, which analyze single genes or
      candidate pathways, cannot be considered ideal because the overall
      pharmacological effects of drugs typically are not dependent on monogenic traits.
      Therefore, to identify the multigenetic influence on drug response, researchers
      and clinicians from different fields of medicine and pharmacology have started to
      perform pharmacogenomic studies employing innovative whole-genome, high
      throughput technologies. In nephrology, only few pharmacogenomics reports have
      been published to date, suggesting the need to enlarge the number of projects and
      increase the research budget for this important research field. In the future, we
      would expect that by applying the knowledge about an individual's inherited
      response to drugs, nephrologists will be able to prescribe medications based on
      each person's genetic makeup, to carefully monitor the efficacy and toxicity of a
      given drug, and to modify the dose and number of medications to obtain predefined
      clinical outcomes.

PMID- 20672233
TI  - [Isolated microhematuria: biopsy, yes or no?].
AB  - Isolated asymptomatic hematuria is frequently encountered in clinical practice
      but there are no established recommendations for its evaluation and management.
      There is controversy regarding which tests are necessary and whether renal biopsy
      is indicated. In the pediatric population, renal biopsy should be considered if
      there is evidence of progressive renal disease or when parents are worried about
      their child's diagnosis or prognosis. In adults, examinations for isolated
      microhematuria should include exclusion of pharmacological causes, journeys to
      endemic areas for S. haematobium or tuberculosis, sickle-cell disease,
      endometriosis and, in patients older than 40 years, kidney, ureteral or bladder
      cancer. Examination of urinary sediment may help in identifying the origin of
      microhematuria. If it is decided to perform a renal biopsy, the patient should be
      carefully informed of the possible complications of renal biopsy, including the
      possibility of finding normal renal tissue.

PMID- 20672234
TI  - [Incremental peritoneal dialysis: a common solution for different types of
      patients].
AB  - It is still a matter of debate whether peritoneal dialysis should be initiated
      with a full dose regimen or with incremental doses. The use of low-dose dialysis
      is not always feasible, but it may have the advantages of improved quality of
      life and lower infective and metabolic complication rates. However, incremental
      peritoneal dialysis has to meet the minimal suggested adequacy targets in terms
      of depuration (Kt/V, creatinine clearance), ultrafiltration, and electrolyte
      balance. Incremental peritoneal dialysis has been proved feasible and safe in
      asymptomatic patients with a glomerular filtration rate (GFR)<6 mL/min, but the
      residual renal function has to be monitored strictly. A second population is
      composed of asymptomatic, mostly older patients with GFR between 6 and 10 mL/min,
      in whom a low-dose start may preserve the residual renal function and favor a
      more gradual training. Lastly, patients with severe, terminal, chronic
      cardiomyopathy who are not candidates for a heart transplant may experience
      beneficial effects on cardiac function and hospitalization with low-dose
      peritoneal dialysis treatment even when they have GFR>10 mL/min. In conclusion,
      incremental peritoneal dialysis is a feasible therapeutic option that the
      nephrologist should know and be able to perform in those patients who may benefit
      from it.

PMID- 20672235
TI  - [Dialysis dose quantification in critically ill patients].
AB  - Acute kidney injury affects about 35% of intensive care unit patients. Renal
      replacement therapy is required in about 5% of such patients and is associated
      with a mortality rate as high as 50% to 80%. The latter is likely more related to
      the failure of extrarenal organs than to an insufficient dialysis dose. This
      could explain, at least in part, the findings of 2 recent trials (VA/ NIH and
      RENAL) where the expected dose-outcome relationship was not confirmed. These
      results cannot be taken to infer that assessing the dialysis dose is no longer
      required. The contrary is true, in that the common finding of large differences
      between prescribed and delivered doses calls for accurate dose assessment, at
      least to avoid underdialysis. The minimum adequate levels are now a Kt/V urea of
      1.2 to 1.4 three times a week (3x/wk) on intermittent hemodialysis (IHD), and an
      effluent of 20 mL/kg/h for 85% of the time on continuous renal replacement
      therapy (CRTT). Both these parameters can be easily measured but are far from
      ideal indices because they account neither for residual renal function nor for
      irregular dose delivery. The equivalent renal urea clearance (EKRjc), by
      expressing the averaged renal+dialytic urea clearance over the whole treatment
      period, is able to account for the above factors. Although assessing EKRjc is
      quite complex, for regular 3x/wk IHD one could use the formula EKRjc=10 Kt/V+1 to
      compute that a Kt/V of 1.2 and 1.4 corresponds to an EKRjc of 13 and 15 mL/min,
      respectively. On the other hand, the hourly effluent per kg is numerically
      similar to EKRjc. On this basis it can be calculated that in non-prediluted
      really continuous treatment, the recommended CRRT dose (EKRjc=20 mL/min) is 33%
      higher than the EKRjc of 15 mL/min, corresponding to the recommended Kt/V of 1.4
      on 3x/wk IHD.

PMID- 20672236
TI  - [Comparative study of the short-term effect of mineral water on calcium
      metabolism].
AB  - Mineral water may be a useful means to achieve optimal dietary calcium intake,
      but the effect of different mineral waters on calcium metabolism is unknown. We
      therefore evaluated calcium excretion in 24-hour urine in 10 healthy individuals
      (5 women and 5 men) after two weeks of drinking at least 1500 mL/day of mineral
      water with a low electrolyte content or 1500 mL/day of mineral water rich in
      calcium and bicarbonate but with a different sodium content. The low-sodium water
      Sangemini was one of these two mineral waters. Calcium excretion did not
      significantly increase after intake of the Sangemini mineral water in comparison
      with the baseline period of low-electrolyte mineral water intake. Conversely, the
      calcium excretion increased significantly after intake of the second mineral
      water. The plasma concentration of C-terminal telopeptide of type I collagen and
      the urinary phosphate excretion decreased after intake of the second mineral
      water in comparison with the baseline period, whereas they did not decrease after
      intake of Sangemini water. Therefore, phosphate excretion was higher after
      drinking Sangemini water than the other studied mineral water. Drinking Sangemini
      water may have a slight effect on calcium excretion and may not inhibit bone
      turnover in the short term. The lesser effect of Sangemini water on calcium
      excretion could be useful in the treatment of osteoporosis.

PMID- 20672237
TI  - [Clinical trials (Part I)].

PMID- 20672238
TI  - [A case of drug-induced syndrome of inappropriate secretion of antidiuretic
      hormone].
AB  - The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is
      characterized by hyponatremia, plasma hypo-osmolality, a urine sodium
      concentration >30-40 mmol/L, normal acid-base balance, a normal plasma potassium
      concentration and, frequently, hypouricemia. There are different types of SIADH:
      idiopathic, iatrogenic, and forms caused by central nervous system or lung
      disorders, neoplasia and major surgical interventions. Drug-induced SIADH is
      becoming the most frequent cause of hyponatremia encountered in clinical
      practice. Here we report the case of a 60-year-old man in a coma (I-II) and with
      very severe hyponatremia (99 mmol/L) due to SIADH induced by fluphenazine and
      amitriptyline, which he had been taking since many years as antidepressant drugs.
      SIADH became very quickly more severe due to the recent administration of
      cisplatin. There was rapid improvement of the clinical symptoms after withdrawal
      of the drugs involved and correction of hyponatremia. In conclusion, in rare
      cases like the present one hyponatremia related to SIADH may be so severe as to
      represent a true clinical emergency. The administration of drugs known to cause
      hyponatremia should be avoided, if possible; otherwise, very careful monitoring
      of the plasma sodium concentration is mandatory to avoid severe neurological
      complications which may lead to the death of the patient.

PMID- 20672239
TI  - [Acute renal failure in the course of Hashimoto's thyroiditis].
AB  - Hashimoto's thyroiditis is the commonest form of autoimmune thyroiditis in the
      world. It occurs most frequently in women (female/male ratio, 6:1) in the age
      group between 30 and 60 years. Here we report the case of a 38-year-old Caucasian
      man who presented with a few days' history of upper limb paresthesias, widespread
      joint and muscle pain, and headaches. Laboratory findings showed increased CPK,
      myoglobin and plasma creatinine levels with acute renal failure. Low free T3 and
      T4 values associated with a high TSH value, the presence of antithyroid globulin
      and peroxidase autoantibodies pointed to a diagnosis of hypothyroidism with
      Hashimoto's thyroiditis. Treatment with levothyroxine was initiated and within 2
      months normalization of renal function, myoglobin, CPK and thyroid hormone levels
      was observed.

PMID- 20672240
TI  - [50 years of nephrology: between science and organizing activities].
AB  - The contribution of Italians to the development of nephrology has been very
      important but not always recognized. Thus, historical accounts do not mention the
      fact that the concept of short dialysis (4 hours 3 times weekly) was invented in
      Parma in 1971 by the Italian nephrologist V. Cambi at the nephrology unit of the
      University Hospital chaired by Prof. L. Migone, although short dialysis is now
      the standard dialysis all over the world. Poorly known facts concerning the
      Italian Society of Nephrology (SIN) described in this paper include the proposal,
      in 1980, of the creation of a new scientific society of nephrology made up only
      of university doctors, which was rejected but a college of university professors
      of nephrology created instead; and the reduction, in 1986, of the duration of the
      term of office of the SIN president from 3 to 2 years, with a hospital and a
      university nephrologist serving alternating terms. Poorly known facts concerning
      EDTA-ERA include the action to involve the presidents of the national societies
      of nephrology in Europe in the organization of EDTA congresses to prevent the
      creation of a new European society of nephrology, the result of which was the
      transformation, in 1983, of EDTA into EDTA-ERA (European Renal Association). On
      20 November 2001 the Fondazione Italiana del Rene (FIR) was founded in Naples,
      which subsequently (on 16 September 2009) became a foundation of the SIN.

PMID- 20672241
TI  - [Female nephrologist in Italy: elements on which to reflect].

PMID- 20672244
TI  - Sickness absence and full return to work after cancer: 2-year follow-up of
      register data for different cancer sites.
AB  - OBJECTIVE: Cancer survival has improved in recent years, but data on return to
      work (RTW) after cancer are sparsely published. Therefore, this study analysed
      RTW after cancer. METHODS: Employees diagnosed with breast cancer, genital
      cancer, gastro-intestinal cancer, lung cancer, skin cancer, or blood malignancies
      were selected from an occupational health register. Sickness absence was followed
      for 2 years after diagnosis and full RTW at equal earnings as before sickness
      absence was assessed for each cancer site using Cox proportional hazards
      regression analysis stratifying for age and gender. RESULTS: 3701 (73%) of 5074
      employees with cancer had full RTW after a median duration of 290 days. Employees
      with lung cancer had the longest duration of sickness absence and only 45% of
      them had full RTW 2 years after diagnosis compared with 88% of employees with
      genital cancer and 87% of employees with skin cancer. Age was associated with the
      time to full RTW among employees with genital cancer: women aged>=35 years had a
      longer time to full RTW compared with women <35 years and men aged>=55 years had
      a longer time to full RTW compared with men <35 years. Gender was associated with
      the time to full RTW among survivors of blood malignancies with women having a
      longer time to full RTW than men. CONCLUSIONS: Most employees had full RTW within
      2 years after the diagnosis of cancer and the time to RTW was largely independent
      of age and gender.

PMID- 20672245
TI  - Patterns, correlates, and prognostic significance of quality of life following
      breast cancer.
AB  - OBJECTIVE: To describe quality of life (QOL) over a 12-month period among women
      with breast cancer, consider the association between QOL and overall survival
      (OS), and explore characteristics associated with QOL declines. METHODS: A
      population-based sample of Australian women (n=287) with invasive, unilateral
      breast cancer (Stage I+) was observed prospectively for a median of 6.6 years.
      QOL was assessed at 6, 12, and 18 months post-diagnosis, using the Functional
      Assessment of Cancer Therapy, Breast (FACT-B+4) questionnaire. Raw scores for the
      FACT-B+4 and subscales were computed and individuals were categorized according
      to whether QOL declined, remained stable or improved between 6 and 18 months.
      Kaplan-Meier and Cox proportional hazards survival methods were used to estimate
      OS and its associations with QOL. Logistic regression models identified factors
      associated with QOL decline. RESULTS: Within FACT-B+4 subscales, between 10% and
      23% of women showed declines in QOL. Following adjustment for established
      prognostic factors, emotional well-being and FACT-B+4 scores at 6 months post
      diagnosis were associated with OS (p<0.05). Declines in physical (p<0.01) or
      functional (p=0.02) well-being between 6 and 18 months post-diagnosis were also
      associated significantly with OS. Receiving multiple forms of adjuvant treatment,
      a perception of not handling stress well and reporting one or more other major
      life events at 6 months post-diagnosis were factors associated with declines in
      QOL in multivariable analyses. CONCLUSIONS: Interventions targeted at preventing
      QOL declines may ultimately improve quantity as well as quality of life following
      breast cancer.

PMID- 20672243
TI  - Do treatment effects vary among differing baseline depression criteria in
      depression in Alzheimer's disease study +/- 2 (DIADS-2)?
AB  - OBJECTIVE: To determine if the effect of sertraline in the depression in
      Alzheimer's disease study - 2 (DIADS-2) differed in subgroups of patients defined
      by baseline depression criteria. METHODS: DIADS-2 was a randomized, parallel,
      placebo-controlled, multicenter trial designed to evaluate the efficacy and
      safety of sertraline (target dose of 100 mg/day) for the treatment of depression
      in patients with Alzheimer's disease. DIADS-2 enrolled 131 patients who met
      criteria for the depression of Alzheimer's disease (dAD). Analyses reported here
      examined if the effect of sertraline differed in various subgroups, including
      those meeting criteria for major depressive episode (MaD), minor depressive
      episode (MiD), and Alzheimer's-associated affective disorder (AAAD) at baseline.
      RESULTS: At baseline, 52 of 131 participants (39.7%) met criteria for MaD, 54
      (41.2%) for MiD, and 90 (68.7%) for AAAD. For the primary outcome of modified
      Alzheimer's Disease Cooperative Study Clinical Global Impression of Change (mADCS
      CGIC) scores at 12 weeks of follow-up, the odds of being at or better than a
      given mADCS-CGIC category did not significantly differ between the two treatment
      groups for those patients with MaD at baseline (OR(sertraline)  = 0.66 [95% CI:
      0.24, 1.82], p = 0.42); tests for interactions between treatment group and
      baseline depression diagnostic subgroup were not significant for MaD versus MiD
      versus neither (chi(2)  = 1.05 (2df), p = 0.59) or AAAD versus no AAAD (chi(2)  =
      0.06 (1df), p = 0.81). CONCLUSIONS: There was no evidence that sertraline
      treatment was more efficacious in those patients meeting baseline criteria for
      MaD compared to MiD or to neither.

PMID- 20672246
TI  - Interest in a group psychotherapy program among Philippine breast cancer patients
      and its associated factors.
AB  - OBJECTIVE: A wide variety of psychosocial interventions are available for cancer
      patients, among which group psychotherapy (GPT) programs have made improvements
      in cancer patients' quality of life, coping abilities, and emotional distress.
      Few research data are available describing Philippine breast cancer patients'
      interest in GPT. This study aimed at enumerating the factors that determine
      Philippine breast cancer patients' interest in a GPT program. METHODS: Patients
      recruited from the University of Santo Tomas Hospital Benavides Cancer Institute
      were asked to answer a survey questionnaire about their demographic, clinical,
      and psychosocial status, as well as whether they would be interested in joining
      GPT and why. RESULTS: Of 135 patients approached, 123 patients completed the
      survey. 104 (85%) women indicated interest in GPT. Patients were mostly
      interested because they wanted to learn coping skills (79%) and gain knowledge or
      information in dealing with cancer (69%). Patients said they were 'very
      interested' in learning about cancer recurrence (96%) and treatments (94%).
      Bivariate analysis showed that compared to the uninterested group, interested
      patients were younger, more likely to be married, and were more likely to have
      used complementary therapy for breast cancer. Logistic regression showed that
      married women were more likely to be interested in GPT (OR 3.30, CI 1.07-10.20).
      CONCLUSION: There is a potentially high interest in GPT among Philippine breast
      cancer patients. The attributes of Philippine patients interested in GPT are
      similar to and yet unique, compared to other populations. Copyright (c) 2010 John
      Wiley & Sons, Ltd.

PMID- 20672247
TI  - The effects of California minimum nurse staffing laws on nurse labor and patient
      mortality in skilled nursing facilities.
AB  - This article investigates how a change in minimum nurse staffing regulation for
      California skilled nursing facilities (SNFs) affects nurse employment and how
      induced changes in nurse staffing affect patient mortality. In 2000, legislation
      increased the minimum nurse staffing standard and altered the calculation of
      nurse staffing, which created incentives to shift employment to lower skilled
      nurse labor. SNFs constrained by the new regulation increase absolute and
      relative hours worked by the lowest skilled type of nurse. Using this regulation
      change to instrument for measured nurse staffing levels, it is determined that
      increases in nurse staffing reduce on-site SNF patient mortality.

PMID- 20672248
TI  - PPARgamma inhibits inflammatory reaction in oxidative stress induced human
      diploid fibloblast.
AB  - The ageing of an inevitable life function is an unavoidable regressive physical
      process. Peroxisome proliferator-activated receptors (PPARs) are members of the
      nuclear hormone receptor family. PPARgamma plays an important role in regulating
      several metabolic pathways. Recently, PPARgamma has been implicated in
      inflammatory responses and age-related diseases. The aim of this study was to
      determine the anti-inflammatory reaction of PPARgamma in an induced ageing
      progress. The late passage of human diploid fibroblasts (HDF), an in vitro ageing
      model, reveals the biological index materials of ageing. Aged cells showed
      decreased PPARgamma expression and elevated levels of intracellular adhesion
      molecule-1 (ICAM-1), an inflammatory molecule. To induce the aged cell phenotype,
      the middle stage of HDF cells (PD31) were induced stress induced premature
      senescence (SIPS) with 200 microM H(2)O(2) for 2 h. SIPS-HDF cells showed high
      levels of ICAM-1, extracellular signal regulated kinase (ERK1/2) activity and
      matrix metallomatrix protease (MMP-2, -9) activity, and low levels of PPARgamma
      expression. A reconstitution of SIPS HDF cells with Ad/PPARgamma resulted in the
      downregulation of ICAM-1, ERK1/2, MMP-2 and -9, and normalized growth of SIPS-HDF
      cells. Moreover, PPARgamma in aged HDF cells reduced pro-inflammatory molecules
      and eliminated the formation of reactive oxygen species (ROS) through the ERK1/2
      pathway. These results strongly suggest that PPARgamma plays a key role in age
      related inflammation and may have clinical applications as a molecular target in
      the treatment of age-related inflammation.

PMID- 20672249
TI  - Social cognition in eating disorders: encoding and representational processes in
      binging and purging patients.
AB  - OBJECTIVE: The present study investigates social cognition impairments in 29
      women with bingeing/purging spectrum eating disorders (ED) compared to 27 healthy
      controls. METHOD: Measures were used to examine encoding and representational
      processes in relation to affect perception and affect attribution, as well as the
      ability to recognize mental causality in social relationships. RESULTS: ED
      patients failed to correctly encode causality in interpersonal relations,
      exhibited deficits in their ability to ascribe behaviour to mental states, and
      showed a greater tendency to attribute negative affects in interpersonal
      relationships. Stepwise regression analyses suggested that ED symptoms could
      account for deficits in the recognition of causality in interpersonal relations.
      CONCLUSIONS: In addition to addressing ED symptoms, social cognition deficits
      should be addressed in the psychological treatment of EDs.

PMID- 20672250
TI  - Psychosocial characteristics in relation to disordered eating attitudes in greek
      adolescents.
AB  - The study explores possible links between eating attitudes in Greek adolescents
      and certain psychosocial characteristics such as self-esteem, empathy and
      anxiety. A total of 202 students (109 boys and 93 girls), 15-18 years old, have
      been recruited. The following questionnaires were used: the Eating Attitudes Test
      (EAT-26), the State-Trait Anxiety Inventory, the Self-Perception Profile for
      Adolescents, the Multidimensional Body-Self-Questionnaire-Overweight
      Preoccupation and the Index of Empathy of Children and Adolescents. The EAT-26
      revealed that 18.3% of the total sample of students (12.8% of boys and 24.7% of
      girls) reported having disordered eating attitudes. Adolescents with disordered
      eating attitudes had significantly higher levels of anxiety and scored less in
      self-reported physical appearance and romantic appeal. Empathy and global self
      esteem did not differ significantly between the two groups. Adolescents with
      disordered eating attitudes have certain psychosocial characteristics which
      differentiate them from the students with healthier eating attitudes.

PMID- 20672251
TI  - Improved process analytical technology for protein a chromatography using
      predictive principal component analysis tools.
AB  - Protein A chromatography is widely employed for the capture and purification of
      antibodies and Fc-fusion proteins. Due to the high cost of protein A resins,
      there is a significant economic driving force for using these chromatographic
      materials for a large number of cycles. The maintenance of column performance
      over the resin lifetime is also a significant concern in large-scale
      manufacturing. In this work, several statistical methods are employed to develop
      a novel principal component analysis (PCA)-based tool for predicting protein A
      chromatographic column performance over time. A method is developed to carry out
      detection of column integrity failures before their occurrence without the need
      for a separate integrity test. In addition, analysis of various transitions in
      the chromatograms was also employed to develop PCA-based models to predict both
      subtle and general trends in real-time protein A column yield decay. The
      developed approach has significant potential for facilitating timely and improved
      decisions in large-scale chromatographic operations in line with the process
      analytical technology (PAT) guidance from the Food and Drug Administration (FDA).

PMID- 20672252
TI  - Using spatial accessibility to identify polyclinic service gaps and volume of
      under-served population in Singapore using Geographic Information System.
AB  - Primary care services in Singapore are provided by 18 Government-funded
      polyclinics and about 1200 private General Practitioners (GPs). This study aims
      to examine the spatial accessibility to polyclinics and identify service gaps,
      and suggest optimal sites using Geographic Information System (GIS) to aid in
      future planning. A national database containing 3.6 million polyclinic visits in
      2006 were geo-analysed using ArcView GIS. Patients' travel impedance to the
      nearest polyclinic was computed using DriveTime to identify areas with the lowest
      spatial accessibility and highest volume of under-served population. Jurong West
      and Sembawang were ranked as top areas with poor spatial accessibility to
      polyclinic services. ArcGIS was used to identify optimal sites with the minimum
      accumulated distance impedance to this under-served population. If new facilities
      were set up at these identified sites, volume of visits by Jurong West and
      Sembawang patients who could access the nearest polyclinics within 4 km Euclidean
      distance from their residence would total at 123 000 and 93 000, respectively.
      Future efforts in polyclinic planning should take this into consideration to
      maximize patients' benefits and minimize patients' travelling costs in order to
      achieve social equity on healthcare access.

PMID- 20672254
TI  - The effect of a motor-based, social skills intervention for adolescents with high
      functioning autism: two single-subject design cases.
AB  - The purpose of this study was to assess the effect of a motor-based, social
      skills intervention for two adolescents with high-functioning autism (HFA) using
      single-subject design. A description of the intervention is provided as a first
      step in the manualization process. The intervention was provided as a 7-week
      after-school program, once weekly to the paired participants. Intervention
      consisted of role-play methods in which motor behaviours were linked with their
      cognitive and emotional meanings. Baseline, intervention and 3-month probe data
      collection periods were carried out and then compared using visual inspection of
      graphed data, paired t-tests and a three-standard-deviation-band approach. Both
      participants displayed a statistically significant increase in targeted social
      skills behaviours from baseline to intervention and maintained this level at a 3
      month post-intervention probe. These single-subject design cases illustrate that
      motor-based, social skills interventions may be effective for adolescents with
      HFA and warrant further testing.

PMID- 20672253
TI  - NY-ESO-1 protein glycosylated by yeast induces enhanced immune responses.
AB  - Vaccine strategies that target dendritic cells to elicit potent cellular immunity
      are the subject of intense research. Here we report that the genetically
      engineered yeast Saccharomyces cerevisiae, expressing the full-length tumour
      associated antigen NY-ESO-1, is a versatile host for protein production. Exposing
      dendritic cells (DCs) to soluble NY-ESO-1 protein linked to the yeast a
      agglutinin 2 protein (Aga2p) protein resulted in protein uptake, processing and
      MHC class I cross-presentation of NY-ESO-1-derived peptides. The process of
      antigen uptake and cross-presentation was dependent on the glycosylation pattern
      of NY-ESO-1-Aga2p protein and the presence of accessible mannose receptors. In
      addition, NY-ESO-1-Aga2p protein uptake by dendritic cells resulted in
      recognition by HLA-DP4 NY-ESO-1-specific CD4(+) T cells, indicating MHC class II
      presentation. Finally, vaccination of mice with yeast-derived NY-ESO-1-Aga2p
      protein led to an enhanced humoral and cellular immune response, when compared to
      the bacterially expressed NY-ESO-1 protein. Together, these data demonstrate that
      yeast-derived full-length NY-ESO-1-Aga2p protein is processed and presented
      efficiently by MHC class I and II complexes and warrants clinical trials to
      determine the potential value of S. cerevisiae as a host for cancer vaccine
      development.

PMID- 20672255
TI  - The impact of stroke: insights from patients in Taiwan.
AB  - Clinical stroke trials have been increasing interest in patient-centred
      assessments such as functional status and health-related quality of life. There
      is a consensus that these measurement factors must be relevant to, and obtained
      from, the patients of interest. The main purpose of this study was to evaluate
      the patients' reactions and concerns that individuals experience after having had
      a stroke. A focus group and individual interviews were conducted to identify and
      describe the patients' reactions to living with the results of a stroke. One
      hundred twelve patients participated in the study. Fifteen factors were
      identified as problems for the 112 participants. For the level of impact and
      importance, the highest percentages of responses rated by the participants in
      each factor were all towards the physical aspects of functioning such as hand/arm
      function and mobility. These findings provide important information on the impact
      of stroke that could be useful for occupational therapists in treatment planning
      and outcome measurement. Further research is recommended to understand the impact
      of a stroke on an individual's adjustment at home and in the community.

PMID- 20672256
TI  - Effectiveness of group music intervention against agitated behavior in elderly
      persons with dementia.
AB  - OBJECTIVES: This study explored the effectiveness of group music intervention
      against agitated behavior in elderly persons with dementia. METHODS: This was an
      experimental study using repeated measurements. Subjects were elderly persons who
      suffered from dementia and resided in nursing facilities. In total, 104
      participants were recruited by permuted block randomization and of the 100
      subjects who completed this study, 49 were in the experimental group and 51 were
      in the control group. The experimental group received a total of twelve 30-min
      group music intervention sessions, conducted twice a week for six consecutive
      weeks, while the control group participated in normal daily activities. In order
      to measure the effectiveness of the therapeutic sessions, assessments were
      conducted before the intervention, at the 6th and 12th group sessions, and at 1
      month after cessation of the intervention. Longitudinal effects were analyzed by
      means of generalized estimating equations (GEEs). RESULTS: After the group music
      therapy intervention, the experimental group showed better performance at the 6th
      and 12th sessions, and at 1 month after cessation of the intervention based on
      reductions in agitated behavior in general, physically non-aggressive behavior,
      verbally non-aggressive behavior, and physically aggressive behavior, while a
      reduction in verbally aggressive behavior was shown only at the 6th session.
      CONCLUSIONS: Group music intervention alleviated agitated behavior in elderly
      persons with dementia. We suggest that nursing facilities for demented elderly
      persons incorporate group music intervention in routine activities in order to
      enhance emotional relaxation, create inter-personal interactions, and reduce
      future agitated behaviors.

PMID- 20672257
TI  - Polyoxometalate-based N-heterocyclic carbene (NHC) complexes for palladium
      mediated C-C coupling and chloroaryl dehalogenation catalysis.

PMID- 20672258
TI  - A new class of singlet carbene ligands.

PMID- 20672259
TI  - Isomerization of triphenylmethoxyl: the Wieland free-radical rearrangement
      revisited a century later.

PMID- 20672260
TI  - A direct entry to substituted N-methoxyamines from N-methoxyamides via N
      oxyiminium ions.

PMID- 20672261
TI  - Solid-state (17)O NMR spectroscopy of large protein-ligand complexes.

PMID- 20672262
TI  - Metal complexes of chiral Mobius aromatic [28]hexaphyrin(1.1.1.1.1.1):
      enantiomeric separation, absolute stereochemistry, and asymmetric synthesis.

PMID- 20672263
TI  - Progress in the chromogenic detection of carbon monoxide.

PMID- 20672264
TI  - Direct amination of secondary alcohols using ammonia.

PMID- 20672266
TI  - One-step conversion of aromatic hydrocarbon bay regions into unsubstituted
      benzene rings: a reagent for the low-temperature, metal-free growth of single
      chirality carbon nanotubes.

PMID- 20672265
TI  - Gold(I)-catalyzed cycloisomerization of enynes containing cyclopropenes.

PMID- 20672267
TI  - A multi-faceted approach to elucidate the crystal structure of D-ribose:
      similarities to protein structure determination.

PMID- 20672268
TI  - From bis(N-alkylimidazole) to bis(NH-NHC) in rhenium carbonyl complexes.

PMID- 20672269
TI  - Cobalt-catalyzed asymmetric hydrovinylation.

PMID- 20672270
TI  - Organocatalytic asymmetric inverse-electron-demand Diels-Alder reaction of
      electron-deficient dienes and crotonaldehyde.

PMID- 20672271
TI  - Metal-free direct asymmetric aminoxylation of aldehydes catalyzed by a binaphthyl
      based chiral amine.

PMID- 20672272
TI  - Functionalization of methane in anaerobic microorganisms.

PMID- 20672273
TI  - Isomerization-induced asymmetric coordination chemistry: from auxiliary control
      to asymmetric catalysis.

PMID- 20672274
TI  - Expanding the limits of organoboron chemistry: synthesis of functionalized
      arylboronates.

PMID- 20672275
TI  - Head-to-tail and heteroleptic pentanuclear circular helicates.

PMID- 20672276
TI  - One is lonely and three is a crowd: two coppers are for methane oxidation.

PMID- 20672277
TI  - Glycosyltransferases and their assays.
AB  - Glycosyltransferases (GTs) are a large family of enzymes that are essential in
      all domains of life for the biosynthesis of complex carbohydrates and
      glycoconjugates. GTs catalyse the transfer of a sugar from a glycosyl donor to a
      variety of acceptor molecules, for example, oligosaccharides, peptides, lipids or
      small molecules. Such glycosylation reactions are central to many fundamental
      biological processes, including cellular adhesion, cell signalling and bacterial-
      and plant-cell-wall biosynthesis. GTs are therefore of significant interest as
      molecular targets in chemical biology and drug discovery. In addition, GTs have
      found wide application as synthetic tools for the preparation of complex
      carbohydrates and glycoconjugates. In order to exploit the potential of GTs both
      as molecular targets and synthetic tools, robust and operationally simple
      bioassays are essential, especially as more and more protein sequences with
      putative GT activity but unknown biochemical function are being identified. In
      this minireview, we give a brief introduction to GT biochemistry and biology. We
      outline the relevance of GTs for medicinal chemistry and chemical biology, and
      describe selected examples for recently developed GT bioassays, with a particular
      emphasis on fluorescence-based formats.

PMID- 20672278
TI  - Copper-promoted and copper-catalyzed intermolecular alkene diamination.

PMID- 20672280
TI  - Self-assembling pathway of HiApp fibrils within lipid bilayers.

PMID- 20672281
TI  - Insight into C35 terpene biosyntheses by nonpathogenic Mycobacterium Species:
      functional analyses of three Z-prenyltransferases and identification of
      dehydroheptaprenylcyclines.
AB  - Nonpathogenic Mycobacterium species produce rare cyclic C(35) terpenes that are
      biosynthesized by cyclization of Z-type C(35) polyprenyl diphosphate. To provide
      deeper insight into the biosynthesis of C(35) terpenes, we carried out functional
      analyses of three Z-prenyltransferase homologues in M. vanbaalenii identified by
      genomic analysis. Mvan_3822, a novel bifunctional Z-prenyltransferase,
      biosynthesizes C(35)-heptaprenyl diphosphate as a main product from (E,E)
      farnesyl diphosphate (E,E-FPP) and (E,E,E)-geranylgeranyl diphosphate (E,E,E
      GGPP), but produces a C(50)-decaprenyl diphosphate from geranyl diphosphate.
      Mvan_1705 is a novel Z,E,E-GGPP synthase. In addition, novel cyclic C(35)
      terpenes, (14E)- and (14Z)-dehydroheptaprenylcycline, were identified as minor
      metabolites in nonpathogenic Mycobacterium cells. C(35) terpenes could be
      biosynthesized by two routes, in which E and Z geometric isomers of heptaprenyl
      diphosphate are produced from E,E-FPP and E,E,E-GGPP, and the prenylreductase
      responsible for the biosynthesis of C(35) terpenes could reduce both E and Z
      prenyl residues.

PMID- 20672282
TI  - Characterization of amyloid fibrils of human beta-2-microglobulin by high
      resolution magic-angle spinning NMR.

PMID- 20672283
TI  - Development of a second generation palladium catalyst system for the
      aminocarbonylation of aryl halides with CO and ammonia.

PMID- 20672284
TI  - Rapid screening of lectins for multivalency effects with a glycodendrimer
      microarray.
AB  - Multivalency is an important phenomenon in protein-carbohydrate interactions. In
      order to evaluate glycodendrimers as multivalent inhibitors of carbohydrate
      binding proteins, we displayed them on a microarray surface. Valencies were
      varied from 1 to 8, and corrections were made for the valencies so that all
      surfaces contained the same amount of the sugar ligand. Five different
      carbohydrates were attached to the dendrimers. A series of fluorescent lectins
      was evaluated, and for each of them a binding profile was obtained from a single
      experiment showing both the specificity of the lectin for a certain sugar and
      whether it prefers multivalent ligands or not. Very distinct binding patterns
      were seen for the various lectins. The results were rationalized with respect to
      the interbinding distances of the lectins.

PMID- 20672285
TI  - Metabolic flux analysis of CHO cell metabolism in the late non-growth phase.
AB  - Chinese hamster ovary (CHO) cell cultures are commonly used for production of
      recombinant human therapeutic proteins. Often the goal of such a process is to
      separate the growth phase of the cells, from the non-growth phase where ideally
      the cells are diverting resources to produce the protein of interest.
      Characterizing the way that the cells use nutrients in terms of metabolic fluxes
      as a function of culture conditions can provide a deeper understanding of the
      cell biology offering guidance for process improvements. To evaluate the fluxes,
      metabolic flux analysis of the CHO cell culture in the non-growth phase was
      performed by a combination of steady-state isotopomer balancing and
      stoichiometric modeling. Analysis of the glycolytic pathway and pentose phosphate
      pathway (PPP) indicated that almost all of the consumed glucose is diverted
      towards PPP with a high NADPH production; with even recycle from PPP to G6P in
      some cases. Almost all of the pyruvate produced from glycolysis entered the TCA
      cycle with little or no lactate production. Comparison of the non-growth phase
      against previously reported fluxes from growth phase cultures indicated marked
      differences in the fluxes, in terms of the split between glycolysis and PPP, and
      also around the pyruvate node. Possible reasons for the high NADPH production are
      also discussed. Evaluation of the fluxes indicated that the medium strength,
      carbon dioxide level, and temperature with dissolved oxygen have statistically
      significant impacts on different nodes of the flux network.

PMID- 20672286
TI  - Recreating the perivascular niche ex vivo using a microfluidic approach.
AB  - Stem cell niches are composed of numerous microenvironmental features, including
      soluble and insoluble factors, cues from other cells, and the extracellular
      matrix (ECM), which collectively serve to maintain stem cell quiescence and
      promote their ability to support tissue homeostasis. A hallmark of many adult
      stem cell niches is their proximity to the vasculature in vivo, a feature common
      to neural stem cells, mesenchymal stem cells (MSCs) from bone marrow and adipose
      tissue, hematopoietic stem cells, and many tumor stem cells. In this study, we
      describe a novel 3D microfluidic device (MFD) as a model system in which to study
      the molecular regulation of perivascular stem cell niches. Endothelial cells
      (ECs) suspended within 3D fibrin gels patterned in the device adjacent to stromal
      cells (either fibroblasts or bone marrow-derived MSCs) executed a morphogenetic
      process akin to vasculogenesis, forming a primitive vascular plexus and maturing
      into a robust capillary network with hollow well-defined lumens. Both MSCs and
      fibroblasts formed pericytic associations with the ECs but promoted capillary
      morphogenesis with distinct kinetics. Biochemical assays within the niche
      revealed that the perivascular association of MSCs required interaction between
      their alpha6beta1 integrin receptor and EC-deposited laminin. These studies
      demonstrate the potential of this physiologically relevant ex vivo model system
      to study how proximity to blood vessels may influence stem cell multipotency.

PMID- 20672287
TI  - Editorial: a call for ethical regulation of genetically created organisms (GCOs)
      beyond GMOs.

PMID- 20672288
TI  - Polymerization of insulin-like growth factor-binding protein-1 (IGFBP-1)
      potentiates IGF-I actions in placenta.
AB  - Insulin-like growth factor (IGF)-binding protein-1 (IGFBP-1), the main secretory
      protein of decidua that binds to IGFs and has been shown to inhibit or stimulate
      IGFs' bioactivities. Polymerization, one of the posttranslational modifications
      of IGFBP-1, has been shown to lead to loss of inhibiting effect of IGFBP-1 on IGF
      I actions. The current studies were undertaken to elucidate the effects of
      steroid hormones on IGFBP-1 polymerization in trophoblast cell cultures.
      Placental tissues were obtained during legal, elective procedures of termination
      of pregnancy performed between 7 and 10 weeks of gestation, and primary
      trophoblast cells were separated. IGFBP-1 polymerization was analyzed by SDS-PAGE
      and immunoblotting. IGFBP-1 was polymerized when IGFBP-1 was added to trophoblast
      cell cultures. Polymerization of IGFBP-1 was inhibited by the addition of anti
      tissue transglutaminase antibody into the culture media. There was an increase in
      the intensity of polymerized IGFBP-1 bands with the addition of
      medroxyprogesterone acetate (MPA), while no such difference was observed upon
      treatment with estradiol. MPA also increased the expression of tissue
      transglutaminase on trophoblast cell membranes. IGF-I stimulated trophoblast cell
      migration, while IGFBP-1 inhibited this IGF-I-induced trophoblast response.
      Addition of MPA attenuated the inhibitory effects of IGFBP-1 on IGF-I-induced
      trophoblast cell migration. IGFBP-1 was polymerized by tissue transglutaminase on
      the cell surface of trophoblasts, and MPA increased tissue transglutaminase
      expression on the cell surface and facilitated IGFBP-1 polymerization. These
      results suggest that progesterone might facilitate polymerization of decidua
      secreted IGFBP-1 and increase IGF-I actions at feto-maternal interface, thereby
      stimulating trophoblast invasion of maternal uterus.

PMID- 20672289
TI  - Thrombin promotes actin stress fiber formation in RPE through Rho/ROCK-mediated
      MLC phosphorylation.
AB  - The retinal pigment epithelium (RPE) forms the outer blood-retina barrier (BRB).
      Most retinal diseases involve BRB breakdown, whereupon thrombin contained in
      serum directly contacts the RPE. Thrombin is known to promote actin stress fiber
      formation, an important determinant in eye diseases involving the epithelial
      mesenchymal transition (EMT) and migration of RPE cells, such as proliferative
      vitreoretinopathy. We analyzed thrombin effect on signaling pathways leading to
      myosin light chain (MLC) phosphorylation and actin stress fiber formation in
      primary cultures of rat RPE cells, in order to support a role for thrombin in RPE
      transdifferentiation. MLC phosphorylation was measured by Western blot; actin
      cytoskeleton was visualized using immunofluorescent phalloidin, and Rho GTPase
      activation was assessed by ELISA. We showed that thrombin/PAR-1 induces the time-
      and dose-dependent phosphorylation of MLC through the activation of Rho/ROCK and
      myosin light chain kinase (MLCK). ROCK increased phospho-MLC by phosphorylating
      MLC and by inhibiting MLC phosphatase. Thrombin effect was abolished by the ROCK
      inhibitor Y-27632, whereas MLCK inhibitor ML-7 and PLC-beta inhibitor U73122
      attenuated MLC phosphorylation by ~50%, suggesting the activation of MLCK by PLC
      beta-mediated calcium increase. Additionally, thrombin-induced MLC
      phosphorylation was blocked by the inhibitory PKCzeta pseudosubstrate,
      wortmannin, and LY294002, indicating IP(3)/PKCzeta involvement in the control of
      MLC phosphorylation. Moreover, we demonstrated that thrombin effect on MLC
      induces actin stress fiber formation, since this effect was prevented by
      inhibiting the pathways leading to MLC phosphorylation. We conclude that thrombin
      stimulation of MLC phosphorylation and actin stress fiber formation may be
      involved in thrombin-induced RPE cell transformation subsequent to BRB
      dysfunction.

PMID- 20672291
TI  - Hypovitaminosis D and ethnic differences in insulin resistance.

PMID- 20672290
TI  - Modulation of the development of human monocyte-derived dendritic cells by
      lithium chloride.
AB  - Lithium has been used or explored to treat psychiatric and neurodegenerative
      diseases that are frequently associated with an abnormal immune status. It is
      likely that lithium may work through modulation of immune responses in these
      patients. Because dendritic cells (DC) play a central role in regulating immune
      responses, this study investigated the influence of lithium chloride (LiCl) on
      the development and function of DC. Exposure to LiCl during the differentiation
      of human monocyte-derived immature DCs (iDC) enhances CD86 and CD83 expression
      and increases the production of IL-1beta, IL-6, IL-8, IL-10, and TNF-alpha.
      However, the presence of LiCl during LPS-induced maturation of iDC has the
      opposite effect. During iDC differentiation, LiCl suppresses the activity of
      glycogen synthase kinase (GSK)-3beta, and activates PI3K and MEK. In addition,
      LiCl activates peroxisome proliferator-activated receptor gamma (PPARgamma)
      during iDC differentiation, a pathway not described before. Each of these
      signaling pathways appears to have distinct impact on the differentiating iDC.
      The enhanced CD86 expression by LiCl involves the PI3K/AKT and GSK-3beta pathway.
      LiCl modulates the expression of CD83 in iDC mainly through MEK/ERK, PI3K/AKT,
      and PPARgamma pathways, while the increased production of IL-1beta and TNF-alpha
      mainly involves the MEK/ERK pathway. The effect of LiCl on IL-6/IL-8/IL-10
      secretion in iDC is mediated through inhibition of GSK-3beta. We have also
      demonstrated that PPARgamma is downstream of GSK-3beta and is responsible for the
      LiCl-mediated modulation of CD86/83 and CD1 expression, but not IL-6/8/10
      secretion. The combined influence of these molecular signaling pathways may
      account for certain clinical effect of lithium.

PMID- 20672292
TI  - Does presenting with meconium ileus affect the prognosis of children with cystic
      fibrosis?
AB  - It is a matter of debate as to what extent the long-term outcome of cystic
      fibrosis (CF) is affected by presenting with meconium ileus (MI). We compared
      long-term clinical outcomes of CF children who presented with MI, to those
      presenting with other symptoms (non-MI) in an era of non new-born-screening
      (NBS).We collected annual lung function data between the ages of 8-15 years in
      terms of percent predicted first second forced expired volume (FEV1%pr), percent
      predicted forced vital capacity (FVC%pr), and between the ages of 2-15 years
      annual height and weight Z-scores (HtZ and WtZ respectively) for children
      attending the Royal Brompton Hospital CF clinic. To be included in the study,
      subjects had to have at least five pulmonary function tests and five
      anthropometric measurements recorded over this period.Thirty-eight MI and 76 non
      MI subjects were compared. There were no significant differences in genotype,
      sex, chronic Pseudomonas infection, or pancreatic enzyme use between the two
      groups. The median age of diagnosis was 1 day (MI) versus 7 months (non-MI).
      There was a decline in spirometry and anthropometric variables over the study
      period for both MI and non-MI groups apart from WtZ score in the non-MI group.
      Mixed model analysis adjusting for potential confounders including genotype,
      pancreatic status, sex, chronic Pseudomonas aeruginosa lung infection, and age of
      diagnosis revealed no difference between the two groups in terms of lung function
      and growth during the time period of the study, however there was a non
      significant trend for subjects presenting with MI to do better in all four
      parameters.We conclude that babies presenting with MI have no worse long-term
      outcome than those presenting symptomatically later in infancy, despite having
      undergone invasive procedures in the newborn period. This underscores the
      importance of early diagnosis and treatment in CF.

PMID- 20672293
TI  - Effect of procaterol on Th2-related chemokines production in human monocyte and
      bronchial epithelial cells.
AB  - Procaterol is a beta2-adrenoceptor agonist used as a bronchodilator for the
      treatment of asthma; it also possesses an anti-inflammatory property. As
      chemokines play a pivotal role in inflammation and the pathogenesis of asthma, we
      investigated the effects of procaterol on type 2 helper T cell (Th2)-related
      [macrophage-derived chemokine (MDC) and I-309] and type 1 helper T cell (Th1)
      related chemokines [monokine-induced by IFN-gamma (Mig) and interferon-inducible
      protein 10 (IP-10)] production of THP-1 cells and human primary monocytes. The
      effect on thymus- and activation-regulated chemokine (TARC) production in BEAS-2B
      cells was also evaluated. Nuclear factor kappaB (NF-kappaB) and mitogen-activated
      protein kinase (MAPK) inhibitors were used to ascertain the intracellular signal
      pathways involved, and etazolate, a phosphodiesterase 4 inhibitor, was used to
      assess the correlation between the beta2-adrenoceptor-cAMP pathway and the effect
      on chemokines. In addition, chromatin immunoprecipitation assays (ChIPs) were
      performed to detect histone modification in the TARC promoter region. MDC and I
      309 production of both THP-1 cells and primary human monocytes, as well as TARC
      expression of BEAS-2B cells, were significantly inhibited by procaterol (10(-10)
      10(-7) M); however, procaterol did not suppress Mig and IP-10 expression by THP-1
      cells. MDC secreted by monocytes is associated with the NF-kappaB and MAPK
      signaling pathways, in particular p38- and c-Jun N-terminal kinase (JNK) MAPKs.
      Etazolate blocked the expression of MDC by THP-1 cells and TARC by BEAS-2B cells.
      ChIP assay revealed decreased trimethylation of lysine 4 in histone 3 (H3K4) in
      the TARC promoter region of BEAS-2B cells. In conclusion, procaterol could
      inhibit Th2-related chemokines production in human monocytes and bronchial
      epithelial cells, an effect that may be mediated through not only the NF-kappaB,
      p38, and JNK-MAPK pathways, but also the beta2-adrenoceptor-cAMP pathway. Most
      importantly, the suppressive effect of Th2-related chemokines production by
      procaterol might be regulated via post-transcriptional modification by decreasing
      H3K4 trimethylation.

PMID- 20672294
TI  - Respiratory impedance and bronchodilator response in healthy Italian preschool
      children.
AB  - OBJECTIVE: To define normal values for respiratory resistance (R(rs)) and
      reactance (X(rs)) and bronchodilator response (BDR) in a population of healthy
      Italian preschool children using a commercially available forced oscillation
      device. METHODS: R(rs) and X(rs) were measured in kindergartens in Viterbo,
      Italy. Regression analysis was performed taking into account height, weight, age,
      gender, and reference equations calculated. The coefficient of repeatability (CR)
      between two tests performed 15 min apart was calculated in a subset of children.
      BDR was assessed by repeating the measurements 15 min after the administration of
      200 ug of inhaled salbutamol and calculated as an absolute change in R(rs) and
      X(rs) at 8 Hz, as a percent change in baseline, and as a change in Z-score
      calculated from the reference equations. RESULTS: Lung function was attempted in
      175 healthy children and successful in 163 (81 male, median age 4.8, range 2.9
      6.1 years). R(rs) and X(rs) at 6, 8, and 10 Hz were related to height but not
      other variables. The CR was 1.53 hPa s L(-1) for R(rs8) and 0.91 hPa s L(-1) for
      X(rs8). The 5th percentile for absolute R(rs8) BDR was -3.16 hPa s L(-1), whereas
      the 95th percentile for absolute X(rs8) BDR was 2.25 hPa s L(-1). These cut-off
      values corresponded to a change in the Z-score of -1.88 and 2.48, respectively.
      CONCLUSIONS: We have established reference equations for R(rs) and X(rs) in
      healthy Italian preschool children using forced oscillations. We recommend a
      change in Z-score of -1.88 for R(rs8) and 2.48 for X(rs8) as cut-off values for a
      positive BDR.

PMID- 20672295
TI  - The reciprocal influences of asthma and obesity on lung function testing, AHR,
      and airway inflammation in prepubertal children.
AB  - Although asthma and obesity are among the major chronic disorders their
      reciprocal or independent influences on lung function testing, airways
      hyperresponsiveness (AHR) and bronchial inflammation has not been completely
      elucidated. In 118 pre-pubertal Caucasian children anthropometric measurements
      functional respiratory parameters (flow/volume curves at baseline and after 6
      minute walk test [6MWT]) together with bronchial inflammatory index (FeNO) were
      assessed. The study population was divided into four groups according to BMI and
      the presence or absence of asthma: Obese asthmatic (ObA) Normal-weight asthmatic
      (NwA), Obese non-asthmatic (Ob), non-asthmatic normal-weight children (Nw).
      Baseline PEF and MEF(75) (%-expected) were significantly different across the
      four groups with significantly lower values of MEF(75) in ObA and Ob children
      when compared to Nw children (P = 0.004 and P = .0001, respectively) and this
      independent role of obesity on upper respiratory flows was confirmed by multiple
      analysis of covariance. After 6 MWT respiratory parameters decreased only in ObA
      and NwA children and 12 children presented a positive fall in FEV(1), in contrast
      no changes of respiratory function testing were detected in Ob and Nw children,
      and only 2 Ob children presented a significant fall in FEV(1). FeNO analysis
      demonstrated significantly higher values in ObA and NwA children when compared to
      Ob (P = 0.008 and P = 0.0002, respectively) and Nw children (P = 0.0001 and P =
      0.0003, respectively), although a significant difference was found between Ob and
      Nw children (P = 0.0004). Multiple analysis of covariance confirmed an
      independent role of asthma on this parameter. In conclusion while AHR and airway
      inflammation are clearly associated with an asthmatic status, obesity seems to
      induce reduction of upper airways flows associated with a certain degree of pro
      inflammatory changes.

PMID- 20672297
TI  - Synthesis of anti-microtubule N-(2-Arylindol-7-yl)benzenesulfonamide derivatives
      and their antitumor mechanisms.

PMID- 20672296
TI  - An 18-month study of the safety and efficacy of repeated courses of inhaled
      aztreonam lysine in cystic fibrosis.
AB  - Chronic airway infection with Pseudomonas aeruginosa (PA) causes morbidity and
      mortality in patients with cystic fibrosis (CF). Additional anti-PA therapies are
      needed to improve health status and health-related quality of life. AIR-CF3 was
      an international 18-month, open-label study to evaluate the safety and efficacy
      of repeated courses of aztreonam for inhalation solution (AZLI, now marketed as
      Cayston(r)) in patients aged >= 6 years with CF and PA infection who previously
      participated in one of two Phase 3 studies: AIR-CF1 or AIR-CF2. Patients received
      up to nine courses (28 days on/28 days off) of 75 mg AZLI two (BID) or three
      times daily (TID) based on randomization in the previous trials. 274 patients,
      mean age 28.5 years (range: 8-74 years), participated. Mean treatment adherence
      was high (92.0% BID group, 88.0% TID group). Hospitalization rates were low and
      adverse events were consistent with CF. With each course of AZLI, FEV(1) and
      scores on the Cystic Fibrosis Questionnaire-Revised Respiratory Symptom scale
      improved and bacterial density in sputum was reduced. Benefits waned in the 28
      days off therapy, but weight gain was sustained over the 18 months. There were no
      sustained decreases in PA susceptibility. A dose response was observed; AZLI TID
      treated patients demonstrated greater improvements in lung function and
      respiratory symptoms over 18 months. Repeated intermittent 28-day courses of AZLI
      treatment were well tolerated. Clinical benefits in pulmonary function, health
      related quality of life, and weight were observed with each course of therapy.
      AZLI is a safe and effective new therapy in patients with CF and PA airway
      infection.

PMID- 20672298
TI  - Gain-of-function of Olig transcription factors enhances oligodendrogenesis and
      myelination.
AB  - The basic helix-loop-helix transcription factors Olig1 and Olig2 are required for
      oligodendrocyte specification and differentiation during central nervous system
      (CNS) development but the effects of overexpression of these factors in murine
      development are not well understood. To test whether Olig1 and Olig2 may
      reprogram CNS stem/progenitors toward an oligodendroglial fate for myelination,
      we generated transgenic mice with doxycycline (Dox)-inducible expression of Olig1
      or Olig2 in nestin-expressing stem/progenitor cells of the CNS. Overexpression of
      Olig1 or Olig2 from E8.5 to E12.5 was sufficient to promote the generation of
      platelet-derived growth factor receptor alpha + oligodendrocyte precursors (OPCs)
      in the spinal cord. We also demonstrated that overexpression of Olig2, but not
      Olig1, enhanced the stem/progenitor cell proliferation and generation of
      motoneuron precursors and inhibited the development of V3 interneurons. In the
      postnatal brain, Dox-inducible expression of Olig2 but not Olig1 in nestin+
      stem/progenitors of the subventricular zone increased the generation of OPCs that
      migrated and differentiated into mature oligodendrocytes in the corpus callosum,
      cortex and olfactory bulb, leading to increased and precocious myelination.
      Altogether, our data indicate that Olig2 is a potential therapeutic target to
      enhance myelination and remyelination in the CNS.

PMID- 20672303
TI  - Fluorescence imaging to quantify the fluorescent microspheres in cardiac tissue.
AB  - To quantify the fluorescent microsphere (FM) content in cardiac tissue, which is
      an indicative of blood flow, fluorescence imaging of both sides of the pig heart
      slice was employed. Despite the light scattering inside the tissue and
      contributions from multiple tissue layers to the total emission, it is shown that
      the fluorescence intensity at any pixel is proportional to the FM content and the
      fluorescence image may be transformed to the image of the FM concentration. A
      convenient standard for the emission-FM concentration transformation is proposed.
      The approach has several advantages in comparison with the traditional "digestion
      & extraction" method such as: non-destructiveness, high spatial resolution, high
      throughput, repeatability and simplicity of operation.

PMID- 20672304
TI  - Psychological distress in different social network members of breast and prostate
      cancer survivors.
AB  - The purposes of this investigation were to compare psychological distress among
      cancer survivors' social network members with different relationships with the
      survivors and to compare their reported levels of distress with population norms.
      Participants in this investigation included spouses/significant others (n = 153),
      siblings (n = 11), adult children (n = 25), parents (n = 10), cousins (n = 6),
      and friends/others (n = 10) of English or Spanish speaking women with breast
      cancer and English speaking men with prostate cancer. Network members reported on
      their symptoms of depression, positive and negative affect, anxiety, and
      relationship satisfaction. The psychological distress among all relationship
      types was similar. Spouses, and to a lesser extent, adult children were the only
      groups whose levels of psychological distress were above population norms.
      Relationship satisfaction was negatively associated with social network members'
      psychological distress, and female network members had higher levels of
      depression than male network members due, in part, to higher perceived stress
      among female network members. These findings highlight the need to consider the
      potentially deleterious impact of cancer not just on survivors' spouses, but on
      other social network members as well and to make services available to network
      members who may play an important role in the survivor's care and adjustment.

PMID- 20672305
TI  - Albedo hydrolysis modelling and digestion with reused effluents in the enzymatic
      peeling process of grapefruits.
AB  - BACKGROUND: Until now, the optimisation of enzymatic peeling of grapefruit in the
      reactor has been obtained as the result of the semi-qualitative effects of enzyme
      activity. This work is an attempt to obtain quantified data. The reuse of enzymes
      to reduce costs in this process is unprecedented in the literature and is the aim
      of the present work. RESULTS: The optimal conditions determined for the maximum
      albedo degradation were a temperature of 40.6  degrees C and a time of 13.1 min
      in an enzymatic concentration of 0.067 mL enzymatic preparation per gram of peel
      in each litre of citrate buffer solution. The decrease in relative enzymatic
      activities in reused effluents was determined, as was the increase in activity
      when the enzymes were purified. These increases were 15.5% for polygalacturonase
      and 15.4% for cellulase activity. CONCLUSION: Optimal temperature, time and the
      ratio between peel mass and the enzymatic preparation volume were the best
      conditions for obtaining good peeling efficiency. The effluents from the
      enzymatic peeling process of the grapefruit still contain appreciable enzymatic
      activity after the digestion process. Thus, reusing these effluents while
      maintaining peeling efficacy and a subsequent recovery of the active enzymes by
      ultra-filtration of the effluents is the way to improve the efficiency of the
      process.

PMID- 20672306
TI  - Classifying subgroups of patients with symptoms of acute coronary syndromes: A
      cluster analysis.
AB  - The purpose of the study was to identify subgroups of patients presenting with
      acute coronary syndromes based on symptom clusters. Two hundred fifty-six
      patients completed a symptom assessment in their hospital rooms. Latent class
      cluster analysis and analysis of variance were used to classify subgroups of
      patients according to selected clinical characteristics. Four subgroups were
      identified and labeled as Heavy Symptom Burden, Chest Pain Only, Sweating and
      Weak, and Short of Breath and Weak (model fit chi(2) [130,891, n = 256] = 867.5,
      p = 1.00). The largest group of patients experienced classic symptoms of chest
      pain and shortness of breath but not sweating. Younger patients were more likely
      to cluster in the Heavy Symptom Burden group (F = 5.08, p = .002). Interpretation
      of the clinical significance of these groupings requires further study.

PMID- 20672307
TI  - The impact of vascular leg disorders on physical activity in methadone-maintained
      adults.
AB  - Chronic venous disorders (CVD) and peripheral arterial disease (PAD) may affect
      diverse physical activity domains. How CVD and PAD and other relevant variables
      affect physical activity was examined in 569 opioid-addicted adults. Both CVD and
      PAD were significantly inversely related to daily walking, sports, and active
      living. Effects remained significant in the latent variable regression after
      controlling covariates. Overall activity was very low; most participants walked
      less than a half mile daily and rarely engaged in sports. Motivation for physical
      activity was the strongest predictor (beta = .55) of daily physical activity.
      Health-care professionals promoting physical activity for injection users should
      consider the vascular health of their legs and motivational variables in addition
      to general health.

PMID- 20672308
TI  - Fibronectin inhibits osteoclastogenesis while enhancing osteoclast activity via
      nitric oxide and interleukin-1beta-mediated signaling pathways.
AB  - Osteoclasts are bone-resorbing cells formed by fusion of mononuclear precursors.
      The matrix proteins, fibronectin (FN), vitronectin (VN), and osteopontin (OPN)
      are implicated in joint destruction and interact with osteoclasts mainly through
      integrins. To assess the effects of these matrix proteins on osteoclast formation
      and activity, we used RAW 264.7 (RAW) cells and mouse splenocytes differentiated
      into osteoclasts on tissue culture polystyrene (TCP) or osteologicTM slides pre
      coated with 0.01-20 ug/ml FN, VN, and OPN. At 96 h, osteoclast number and
      multinucleation were decreased on VN and FN compared to OPN and TCP in both RAW
      and splenocytes cell cultures. When early differentiation was assessed, VN but
      not FN decreased cytoplasmic tartrate-resistant acid phosphatase activity and pre
      osteoclast number at 48 h. OPN had the opposite effect to FN on osteoclast
      formation. When RAW cells were differentiated on OPN and treated by FN and OPN,
      osteoclast number only in the FN treated group was 40-60% lower than the control,
      while the total number of nuclei was unchanged, suggesting that FN delays
      osteoclast fusion. In contrast to its inhibitory effect on osteoclastogenesis, FN
      increased resorption by increasing both osteoclast activity and the percentage of
      resorbing osteoclasts. This was accompanied by an increase in nitric oxide (NO)
      levels and interleukin-1beta (IL-1beta). IL-1beta production was inhibited using
      the NO-synthase inhibitor only on FN indicating a FN-specific cross-talk between
      NO and IL-1beta signaling pathways. We conclude that FN upregulates osteoclast
      activity despite inhibiting osteoclast formation and that these effects involve
      NO and IL-1beta signaling.

PMID- 20672309
TI  - Simultaneous color-coded imaging to distinguish cancer "stem-like" and non-stem
      cells in the same tumor.
AB  - In this study, we demonstrate that the differential behavior, including
      malignancy and chemosensitivity, of cancer stem-like and non-stem cells can be
      simultaneously distinguished in the same tumor in real time by color-coded
      imaging. CD133(+) Huh-7 human hepatocellular carcinoma (HCC) cells were
      considered as cancer stem-like cells (CSCs), and CD133(-) Huh-7 cells were
      considered as non-stem cancer cells (NSCCs). CD133(+) cells were isolated by
      magnetic bead sorting after Huh-7 cells were genetically labeled with green
      fluorescent protein (GFP) or red fluorescent protein (RFP). In this scheme,
      CD133(+) cells were labeled with GFP and CD133(-) cells were labeled with RFP.
      CSCs had higher proliferative potential compared to NSCCs in vitro. The same
      number of GFP CSCs and the RFP NSCCs were mixed and injected subcutaneously or in
      the spleen of nude mice. CSCs were highly tumorigenic and metastatic as well as
      highly resistant to chemotherapy in vivo compared to NSCCs. The ability to
      specifically distinguish stem-like cancer cells in vivo in real time provides a
      visual target for prevention of metastasis and drug resistance.

PMID- 20672310
TI  - Indomethacin promotes adipogenesis of mesenchymal stem cells through a
      cyclooxygenase independent mechanism.
AB  - Regulation of mesenchymal stem cell (MSC) lineage selection is important for the
      generation of bone mass. Inhibition of cyclooxygenase-2 (COX2) may increase
      adipogenesis at the cost of decreasing osteoprogenitor output. Here we
      investigated the role of COX2 and its products during MSC differentiation.
      Indomethacin stimulated adipogenesis (increased aP2, adiponectin and lipid
      droplets) of CH310T1/2 stem cells as well as marrow-derived MSCs to a degree
      similar to the PPARgamma2 ligand, rosiglitazone. Unlike rosiglitazone,
      indomethacin significantly upregulated PPARgamma2 expression. Indomethacin and
      the COX2 specific inhibitor celecoxib suppressed PGE2 production, but celecoxib
      did not induce adipogenesis. As well, addition of PGE2 failed to reverse
      indomethacin induced adipogenesis, indicating that indomethacin's effects were
      prostaglandin independent. In MSCs over-expressing PPARgamma2 and RXRalpha,
      indomethacin did not increase PPAR-induced transcription, while rosiglitazone and
      15d-PGJ2 did (1.7- and 1.3-fold, respectively, P < 0.001). We considered whether
      indomethacin might directly affect C/EBPbeta proximally to PPARgamma2 induction.
      Indomethacin significantly increased C/EBPbeta expression and protein within 24 h
      of addition. These results indicate that indomethacin promotes adipogenesis by
      increasing C/EBPbeta and PPARgamma2 expression in a prostaglandin-independent
      fashion. This effect of indomethacin is pertinent to potential deleterious
      effects of this commonly used anti-inflammatory drug on bone remodeling and
      tissue healing.

PMID- 20672312
TI  - Retrograde melting and internal liquid gettering in silicon.

PMID- 20672311
TI  - The cholinergic system in mild cognitive impairment and Alzheimer's disease: an
      in vivo MRI and DTI study.
AB  - Few studies have investigated in vivo changes of the cholinergic basal forebrain
      in Alzheimer's disease (AD) and amnestic mild cognitive impairment (MCI), an at
      risk stage of AD. Even less is known about alterations of cortical projecting
      fiber tracts associated with basal forebrain atrophy. In this study, we
      determined regional atrophy within the basal forebrain in 21 patients with AD and
      16 subjects with MCI compared to 20 healthy elderly subjects using deformation
      based morphometry of MRI scans. We assessed effects of basal forebrain atrophy on
      fiber tracts derived from high-resolution diffusion tensor imaging (DTI) using
      tract-based spatial statistics. We localized significant effects relative to a
      map of cholinergic nuclei in MRI standard space as determined from a postmortem
      brain. Patients with AD and MCI subjects showed reduced volumes in basal
      forebrain areas corresponding to anterior medial and lateral, intermediate and
      posterior nuclei of the Nucleus basalis of Meynert (NbM) as well as in the
      diagonal band of Broca nuclei (P < 0.01). Effects in MCI subjects were spatially
      more restricted than in AD, but occurred at similar locations. The volume of the
      right antero-lateral NbM nucleus was correlated with intracortical projecting
      fiber tract integrity such as the corpus callosum, cingulate, and the superior
      longitudinal, inferior longitudinal, inferior fronto-occipital, and uncinate
      fasciculus (P < 0.05, corrected for multiple comparisons). Our findings suggest
      that a multimodal MRI-DTI approach is supportive to determine atrophy of
      cholinergic nuclei and its effect on intracortical projecting fiber tracts in AD.

PMID- 20672313
TI  - Controlled synthesis of one-dimensional inorganic nanostructures using pre
      existing one-dimensional nanostructures as templates.
AB  - Template-directed strategy has become one of the most popular methods for the
      fabrication of one-dimensional (1D) nanostructures with uniform size and
      controllable physical dimensions in recent years. This Review article describes
      the recent progress in the synthesis of 1D inorganic nanostructures by using
      suitable templates. A brief survey on the templating method based on the organic
      templates and porous membrane is firstly given. Then, the article is focused on
      recent emerging synthetic strategies by templating against the pre-existing 1D
      nanostructures using different physical and chemical transformation techniques,
      including epitaxial growth, nonepitaxial growth, direct chemical transformation,
      solid-state interfacial diffusion reaction, and so on. The important reactivity
      role of the 1D nanostructures will be emphasized in such transformation process.
      Finally, we conclude this paper with some perspectives and outlook on this
      research topic.

PMID- 20672314
TI  - Influence of glutathione-S-transferase theta (GSTT1) and micro (GSTM1) gene
      polymorphisms on the susceptibility of hepatocellular carcinoma in Taiwan.
AB  - BACKGROUND AND OBJECTIVES: Hepatocellular carcinoma (HCC) is one of the most
      frequent malignant neoplasms worldwide and is the second leading cause of cancer
      death in Taiwan. Genetic polymorphism has been reported as a factor for increased
      susceptibility of HCC. Glutathione-S-transferases theta (GSTT1) and micro (GSTM1)
      play essential roles in detoxification of ingested xenobiotics and modulation of
      the susceptibility of gene-related cancer. The aim of this study was to estimate
      the relationships between these two gene polymorphisms and HCC risk and
      clinicopathological status in Taiwanese. METHODS: Polymerase chain reaction (PCR)
      was used to determine gene polymorphisms of 102 patients with HCC and 386 healthy
      controls. RESULTS: Both gene polymorphisms were not associated with the clinical
      pathological status of HCC and serum levels of liver-related clinical
      pathological markers. While no relationship between GSTM1 gene polymorphism and
      HCC susceptibility was found, individuals of age <56 years old with GSTT1 present
      genotype have a risk of 2.77-fold (95% CI: 1.09-7.09) for HCC compared to that
      with null variant, after adjustment for other confounders. CONCLUSIONS: GSTT1 and
      GSTM1 null genotypes do not associate with increased risk of HCC.

PMID- 20672315
TI  - Preoperative dietary restriction reduces hepatic tumor load by reduced E-selectin
      mediated adhesion in mice.
AB  - BACKGROUND: Inflammatory responses facilitate metastasis by increasing expression
      of adhesion molecules. Dietary restriction (30% reduction in daily calorie
      intake) reduces the expression of adhesion molecules and protects against
      surgically induced inflammation. DR might therefore beneficially interfere with
      surgery-induced inflammation and subsequent adhesion of circulating tumor cells.
      METHODS: BALB/c mice were subjected to 2 weeks dietary restriction prior to
      inoculation with tumor cells. Intra-splenic injection of 5.0 x 10(4) C26-colon
      carcinoma cells was followed by splenectomy. Hepatic tumor load was scored after
      10 days as a percentage (tumor surface/total liver surface) on H&E stained
      sections. Liver mRNA expression of adhesion molecules was determined and the
      effect of serum from dietary restriction mice on in vitro tumor growth and
      adhesion capacity was assessed. RESULTS: Preoperative dietary restriction
      significantly reduced mRNA expression levels of E-selectin (P = 0.0087) and
      hepatic tumor load (P = 0.036). Dietary restriction serum did not affect in vitro
      cell growth but reduced in vitro adhesion of C26 cells to endothelial cells (P =
      0.0043). CONCLUSIONS: Preoperative dietary restriction reduces hepatic tumor load
      after injection with tumor cells. Reduced adhesion to endothelial cells and
      reduced mRNA expression of E-selectin suggest that dietary restriction reduces
      tumor load by lowering the adhesion of circulating tumor cells to hepatic
      vascular endothelium.

PMID- 20672316
TI  - High preoperative plasma fibrinogen levels are associated with distant metastases
      and impaired prognosis after curative resection in patients with colorectal
      cancer.
AB  - BACKGROUND: The purpose of this study was to evaluate the association between
      preoperative plasma fibrinogen levels on clinicopathologic parameters and overall
      survival in patients after curative resection with colorectal cancer. METHODS:
      Preoperative plasma fibrinogen levels were examined in 341 patients who underwent
      curative resection for colorectal cancer. Preoperative plasma fibrinogen levels
      were correlated with clinicopathologic findings and disease-specific overall
      survival. RESULTS: Mean (+/-SD) preoperative plasma fibrinogen levels were 369.9
      mg/dl (+/-69.1 mg/dl). Elevated plasma fibrinogen levels were associated with
      advanced tumor stage (P = 0.008), venous invasion (P = 0.006), and postoperative
      distant metastases (P < 0.001), but not with histologic grade (P = 0.232),
      invasion depth (P = 0.253), and lymph node involvement (P = 0.136). Multivariate
      analysis showed that preoperative plasma fibrinogen levels (P = 0.029),
      histologic grade (P = 0.001), and lymph node involvement (P = 0.001) were defined
      as independent prognostic factors. CONCLUSIONS: High preoperative plasma
      fibrinogen levels are associated with distant metastases and impaired prognosis
      after curative resection in patients with colorectal cancer.

PMID- 20672317
TI  - Predictive significance of preoperative serum VEGF-C and VEGF-D, independently
      and combined with Ca19-9, for the presence of malignancy and lymph node
      metastasis in patients with gastric cancer.
AB  - BACKGROUND: Cumulative evidence demonstrate that lymphangiogenic vascular
      endothelial growth factors (VEGF)-C and -D are over-expressed and associated to
      lymph node metastasis (LNM) in gastric cancer. The aim of this study is to
      investigate whether preoperative serum levels of VEGF-C and VEGF-D could be
      useful tumor markers in patients with operable gastric adenocarcinoma. METHODS:
      We prospectively examined serum samples from 40 patients and 40 non-cancer
      controls using enzyme-linked immunosorbent assay (ELISA). Logistic regression
      analysis was implemented. VEGF-C and VEGF-D were studied independently and in
      combination with Ca19-9. RESULTS: In gastric cancer patients, preoperative VEGF-C
      was significantly lower as compared to controls and to postoperative VEGF-C (P <
      0.001); preoperative VEGF-D was significantly higher as compared to controls and
      to postoperative VEGF-D (P < 0.001). ROC curve analysis identified a VEGF-C/VEGF
      D cut-off value of < 2.7 for the presence of gastric cancer, with 83% sensitivity
      and 75% specificity (P < 0.001). Backward stepwise selection modeling including
      sex, age, VEGF-D and Ca19-9, predicted the presence of LNM with 86% sensitivity
      and 82% specificity (P < 0.001). CONCLUSION: Circulating levels of VEGF-C and
      VEGF-D could play a role as biomarkers for serological detection and staging in
      gastric cancer.

PMID- 20672318
TI  - Physical activity and sedentary behavior in adolescents with type 1 diabetes.
AB  - The purpose of this study was to describe the associations between levels of
      physical activity measured by accelerometry and changes in fitness, body
      composition, lipids, and glucose control (i.e., glycosolated hemoglobin [A1C]) in
      a sample of 16 adolescents with type 1 diabetes participating in a personalized
      exercise program. More sedentary activity was associated with lower fitness and
      fat free mass and increased total cholesterol, low-density lipoprotein (LDL-c),
      and triglycerides (p < .05). Greater amounts of moderate to vigorous activity
      were associated with higher fitness and fat free mass, and decreased total
      cholesterol, LDL-c, triglycerides, and A1C (p < .05). Findings support the
      beneficial effects of increased moderate activity and decreased sedentary
      behavior to reduce cardiovascular risks and improve glucose control in
      adolescents with type 1 diabetes.

PMID- 20672319
TI  - L1, beta-catenin, and E-cadherin expression in patients with colorectal cancer:
      correlation with clinicopathologic features and its prognostic significance.
AB  - OBJECTIVE: Currently, there are no clinically used/routine biomarkers that
      accurately predict whether colorectal cancer (CRC) patients will or will not
      respond to adjuvant chemotherapy. The aim of this study was to investigate L1,
      beta-catenin, and E-cadherin expression in patients with CRC and their
      relationship to tumor progression, and to identify patients who will respond to
      chemotherapy. METHODS: A total of 142 patients who underwent surgical treatment
      for CRC were chosen retrospectively. The samples from these patients were
      analyzed by immunohistochemistry. SPSS-14 program package was used for
      statistical calculation. RESULTS: Expression of L1, beta-catenin, and E-cadherin
      were found to be strongly associated with invasion and metastasis of CRC. Cox
      multivariate analysis results indicated that L1 expression and stage of Dukes
      could be considered as the independent prognostic factors for survival.
      Furthermore, our study found that the 5-year survival rate was the significantly
      associated with the expression of L1, beta-catenin (normal and ectopic
      expression), and E-cadherin for Dukes' stage B (P < 0.01) patients. However, no
      such result was found for Dukes' stage A (P > 0.05) and C (P > 0.05) patients.
      CONCLUSION: Our study provided reference for identifying patients who need
      adjuvant chemotherapy. L1, beta-catenin, and E-cadherin could be considered as
      biomarkers to predict whether CRC patients will or will not respond to adjuvant
      chemotherapy.

PMID- 20672320
TI  - Involvement of Akt/NF-kappaB pathway in N6-isopentenyladenosine-induced apoptosis
      in human breast cancer cells.
AB  - N(6)-isopentenyladenosine (i6A) inhibits the tumor cell growth by inducing cell
      apoptosis in various cancer cell lines. However, little is known regarding the
      mechanisms by which the drug induces cell apoptosis. In this study, we further
      explored the molecular mechanisms of i6A as an anticancer agent on a human breast
      cancer cell line MDA MB 231. Treatment with i6A decreased the cell proliferation
      of MDA MB 231 cells in a dose-dependent manner by arresting the cells at
      G(0)/G(1) phase. This effect was strongly associated with concomitant decrease in
      the level of cyclin D1, cyclin E, cdk2, and increase of p21waf1 and p27kip. In
      addition i6A also induced apoptotic cell death by increasing the expression of
      Bax, and decreasing the levels of Bcl-2 and Bcl-xL, and subsequently triggered
      mitochondria apoptotic pathway (release of cytochrome c and activation of caspase
      3). We observed that i6A suppressed the nuclear factor kappaB (NF-kappaB) pathway
      and inhibited the Akt activation. The results of this study indicate that i6A
      decreases cell proliferation and induces apoptotic cell death in human breast
      cancer cells, possibly by decreasing signal transduction through the Akt/NF
      kappaB cell survival pathway.

PMID- 20672321
TI  - Laminin-332 cleavage by matriptase alters motility parameters of prostate cancer
      cells.
AB  - BACKGROUND: Matriptase, a type II transmembrane serine protease, has been linked
      to initiation and promotion of epidermal carcinogenesis in a murine model,
      suggesting that deregulation of its role in epithelia contributes to
      transformation. In human prostate cancer, matriptase expression correlates with
      progression. It is therefore of interest to determine how matriptase may
      contribute to epithelial neoplastic progression. One approach for studying this
      is to identify potential matriptase substrates involved in epithelial integrity
      and/or transformation like the extracellular matrix macromolecule, laminin-332
      (Ln-332), which is found in the basement membrane of many epithelia, including
      prostate. Proteolytic processing of Ln-332 regulates cell motility of both normal
      and transformed cells, which has implications in cancer progression. METHODS: In
      vitro cleavage experiments were performed with purified Ln-332 protein and
      matriptase. Western blotting, enzyme inhibition assays, and mass spectrometry
      were used to confirm cleavage events. Matriptase overexpressing LNCaP prostate
      cancer cells were generated and included in Transwell migration assays and single
      cell motility assays, along with other prostate cells. RESULTS: We report that
      matriptase proteolytically cleaves Ln-332 in the beta3 chain. Substrate
      specificity was confirmed by blocking cleavage with the matriptase inhibitor,
      Kunitz domain-1. Transwell migration assays showed that DU145 cell motility was
      significantly enhanced when plated on matriptase-cleaved Ln-332. Similarly,
      Transwell migration of matriptase-overexpressing LNCaP cells was significantly
      increased on Ln-332 and, as determined by live single-cell microscopy, two
      motility parameters of this cell line, speed and directional persistence, were
      also higher. CONCLUSIONS: Proteolytic processing of Ln-332 by matriptase enhances
      speed and directional persistence of prostate cancer cells.

PMID- 20672322
TI  - PSGR and PCA3 as biomarkers for the detection of prostate cancer in urine.
AB  - BACKGROUND: Several studies have demonstrated the usefulness of monitoring an RNA
      transcript in urine, such as PCA3, for prostate cancer (PCa) diagnosis. PCa
      screening would benefit from additional biomarkers of higher specificity and
      could be used in conjunction with prostate-specific antigen (PSA) testing, in
      order to better determine biopsy candidates. METHODS: We used urine sediments
      after prostate massage (PM) from 215 consecutive patients, who presented for
      prostate biopsy. We tested whether prostate-specific G-protein coupled receptor
      (PSGR), a biomarker previously described to be over-expressed in PCa tissue,
      could also be detected by quantitative real-time PCR in post-PM urine sediment.
      We combined these findings with prostate cancer gene 3 (PCA3), the current gold
      standard for PCa diagnosis in urine, to test if a combination of both biomarkers
      could improve the sensitivity of PCA3 alone. RESULTS: By univariate analysis we
      found that PSGR and PCA3 were significant predictors of PCa. Receiver operator
      characteristic curve analysis and its multivariate extension, multivariate ROC
      (MultiROC), were used to assess the outcome predictive values of the individual
      and the paired biomarkers. We obtained the following area under the curve values:
      PSA (0.602), PSGR (0.681), PCA3 (0.656), and PSGRvPCA3 (0.729). Then, we tested
      whether a combination of PSGR and PCA3 could improve specificity by fixing the
      sensitivity at 95%. We obtained specificities of 15% (PSGR), 17% (PCA3), and 34%
      (PSGRvPCA3). CONCLUSIONS: A multiplexed model including PSGR and PCA3 improves
      the specificity for the detection of PCa, especially in the area of high
      sensitivity. This could be clinically useful for determining which patients
      should undergo biopsy.

PMID- 20672323
TI  - Galectin-3 is a substrate for prostate specific antigen (PSA) in human seminal
      plasma.
AB  - BACKGROUND: Galectin-3 is a multivalent carbohydrate-binding protein involved in
      cell adhesion, cell cycle control, immunomodulation, and cancer progression,
      including prostate cancer. Galectin-3 function is regulated by proteolytic
      cleavage that destroys galectin-3 multivalency while preserving carbohydrate
      binding activity. In human semen, galectin-3 is present in seminal plasma and is
      also associated with prostasomes, exosome-like vesicles secreted by the prostate.
      In the current study, we characterized the proteolytic activity that cleaves
      galectin-3 in human seminal plasma. METHODS: An in vitro assay was developed to
      investigate galectin-3 cleavage in seminal plasma. The effect of protease
      inhibitors, divalent ion chelators, and Zn(2+) on the cleavage activity was
      determined. Proteases enriched from seminal plasma were tested for their ability
      to cleave galectin-3. Affinity purification and microsequence analysis were used
      to identify the cleavage site in galectin-3. RESULTS: Galectin-3 was identified
      in human seminal plasma in an intact and truncated form. Gelatinases enriched
      from seminal plasma did not cleave galectin-3. Inhibitor studies indicated that
      the galectin-3 cleavage activity in seminal plasma is a Zn(2+) sensitive, serine
      protease. Prostate specific antigen (PSA) was demonstrated to cleave galectin-3
      between tyrosine107-glycine108 and produce a functionally active, monovalent
      lectin. CONCLUSIONS: PSA is a chymotrypsin-like serine protease secreted by the
      prostatic epithelium and normally functions in liquefaction of semen following
      ejaculation. Furthermore, PSA is implicated in the promotion of localized
      prostate tumors and bone metastases by its roles in immunomodulation, invasion,
      and apoptosis. Our results indicate that PSA regulates galectin-3 in human semen
      and may regulate galectin-3 function during prostate cancer progression.

PMID- 20672324
TI  - Inhibition of ADAM9 expression induces epithelial phenotypic alterations and
      sensitizes human prostate cancer cells to radiation and chemotherapy.
AB  - INTRODUCTION: Recent studies demonstrated the importance of ADAM9 in prostate
      cancer relapse upon therapy. In this study, we determined the role of ADAM9 in
      the therapeutic resistance to radiation and chemotherapy. MATERIALS AND METHODS:
      ADAM9 was either transiently or stably knocked down in C4-2 prostate cancer
      cells. The sensitivity of ADAM9 knockdown cells toward radiation and
      chemotherapeutic agents were determined. Additionally, the effects of ADAM9
      knockdown on prostate cancer cell morphology, biochemical and functional
      alterations were accessed. RESULTS: Both transient and stable knockdown of ADAM9
      resulted in increased apoptosis and increased sensitivity to radiation. ADAM9
      knockdown also increased prostate cancer sensitivity to several chemotherapeutic
      drugs. ADAM9 knockdown resulted in increased E-cadherin and altered integrin
      expression and underwent phenotypic epithelial transition. These were reflected
      by the morphological, biochemical, and functional alterations in the ADAM9
      knockdown cells. CONCLUSIONS: ADAM9 plays a crucial role in prostate cancer
      progression and therapeutic resistance in part by altering E-cadherin and
      integrin expression. ADAM9 is an important target for the consideration of
      treating prostate cancer patients who developed therapeutic resistance and
      disease relapse.

PMID- 20672325
TI  - Absence of radiographic asbestosis and the risk of lung cancer among asbestos
      cement workers: Extended follow-up of a cohort.
AB  - BACKGROUND: It has been a matter of controversy whether there is an increased
      risk of lung cancer among asbestos-exposed workers without radiographic
      asbestosis. A previous study of lung cancer risk among asbestos-cement workers
      has been updated with an additional 12 years of follow-up. METHODS: Subjects had
      received radiographic examination at 20 and 25 years from first exposure to
      asbestos. Radiographs were interpreted by a single National Institute of Safety
      and Health (NIOSH)-certified B-reader using the 1971 International Labor Office
      (ILO) Classification of the pneumoconioses as reference standard. Asbestosis was
      defined as an ILO coding of 1/0 or higher. Standardized Mortality Ratios (SMRs)
      were calculated using the general population of Ontario as reference. RESULTS:
      Among asbestos-cement workers without radiographic asbestosis at 20 years latency
      the lung cancer SMR was 3.84 (2.24-6.14). Among workers without asbestosis when
      examined at 25 years latency the SMR was 3.69 (1.59-7.26). CONCLUSIONS: Workers
      from an Ontario asbestos-cement factory who did not have radiographic asbestosis
      at 20 or 25 years from first exposure to asbestos continued to have an increased
      risk of death from lung cancer during an additional 12 years of follow-up.

PMID- 20672327
TI  - Akt/protein kinase B in skeletal muscle physiology and pathology.
AB  - The Akt/protein kinase B is critical regulator of cellular homeostasis with
      diminished Akt activity being associated with dysregulation of cellular
      metabolism and cell death while Akt over-activation has been linked to
      inappropriate cell growth and proliferation. Although the regulation of Akt
      function has been well characterized in vitro, much less is known regarding the
      function of Akt in vivo. Here we examine how skeletal muscle Akt expression and
      enzymatic activity are controlled, the role of Akt in the regulation of skeletal
      muscle contraction, stress response glucose utilization, and protein metabolism,
      and the potential participation of this important molecule in skeletal muscle
      atrophy, aging, and cancer.

PMID- 20672326
TI  - Brain natriuretic peptide modulates the delayed rectifier outward K(+) current
      and promotes the proliferation of mouse Schwann cells.
AB  - Brain natriuretic peptide (BNP) may act as a neuromodulator via its associated
      receptors (natriuretic peptide receptors, NPRs) in the central nervous system
      (CNS), but few studies have reported its activity in the peripheral nervous
      system (PNS). In this study, we observed that BNP increased the
      tetraethylammonium chloride (TEA)-sensitive delayed rectifier outward potassium
      current (I(K)) in mouse Schwann cells (SCs) using whole-cell recording
      techniques. At concentrations of 1-100 nM, BNP reversibly activated I(K) in a
      dose-dependent manner, with modulating its steady-state activation and
      inactivation properties. The effect of BNP on I(K) was abolished by preincubation
      with the specific antagonist of NPR-A, and could not be mimicked by application
      of NPR-C agonist. These results were supported by immunocytochemical findings
      indicating that NPR-A was expressed in SCs. The application of 8-Br-guanosine
      3',5'-monophosphate (8-Br-cGMP) mimicked the effect of BNP on I(K), but BNP was
      unable to further increase I(K) after the application of cyclic guanosine
      monophosphate (cGMP). Genistein blocked I(K) and also completely eliminated the
      effects of BNP and cGMP on I(K). The selective K(V)2.1 subunit blocker,
      Jingzhaotoxin-III (JZTX-III), reduced I(K) amplitude by 30%, but did not abolish
      the increase effect of BNP on I(K) amplitude. In addition, BNP significantly
      stimulated SCs proliferation and this effect could be partly inhibited by TEA.
      Together these results suggest that BNP modulated I(K) probably via cGMP- and
      tyrosine kinase-dependent pathways by activation of NPR-A. This effect of BNP on
      I(K) in SCs might partly explain its effect on cell proliferation.

PMID- 20672328
TI  - Expression, localization, and regulation of the neuregulin receptor ErbB3 in
      mouse heart.
AB  - Neuregulins (NRG) belong to the EGF family of growth factors, which are ligands
      of the ErbB receptors. Their expression in the adult heart is essential,
      especially when the heart is submitted to cardiotoxic stress such as that
      produced by anthracyclines. It is considered that ErbB4 is the only NRG receptor
      expressed by the adult heart. Upon binding, ErbB4 may dimerize with ErbB2 to
      generate signals inside cells. However, here we show the presence of ErbB3 in the
      mouse heart from birth to adulthood by Western blotting and real-time RT-PCR. The
      expression level of ErbB3 mRNA was lower than that of ErbB2 or ErbB4, but was
      more stable throughout postnatal development. In isolated heart myocytes, ErbB3
      localized to the Z-lines similarly to ErbB1. Perfusion of isolated hearts with
      NRG-1beta induced phosphorylation of ErbB3, as well as ErbB2 and ErbB4. In adult
      mice, both ErbB2 and ErbB3, but not ErbB1 or ErbB4, were rapidly down-regulated
      upon the induction of heart hypertrophy. In conclusion, our results demonstrate
      that ErbB3, in addition to ErbB4, is a receptor for neuregulin-1beta in the adult
      mouse heart.

PMID- 20672330
TI  - Correlation between anatomical characteristics of ethanol organosolv pretreated
      Buddleja davidii and its enzymatic conversion to glucose.
AB  - Buddleja davidii is a unique biomass that has many attractive agroenergy
      features, especially its wide range of growth habitat. The anatomical
      characteristics of B. davidii were investigated before and after ethanol
      organosolv pretreatment (one of the leading pretreatment technologies) in order
      to further understand the alterations that occur to the cellular structure of the
      biomass which can then be correlated with its enzymatic digestibility. Results
      showed that the ethanol organosolv pretreatment of B. davidii selectively removes
      lignin from the middle lamella (ML), which does not significantly disrupt the
      crystalline structure of cellulose. The removal of ML lignin is a major factor in
      enhancing enzymatic cellulose-to-glucose hydrolysis. The pretreatment also causes
      cell deformation, resulting in cracks and breaks in the cell wall. These
      observations, together with characterization analysis of the cell wall polymer
      material, lend support to the hypothesis that the physical distribution of lignin
      in the biomass matrix is an important structural feature affecting biomass
      enzymatic digestibility.

PMID- 20672329
TI  - alphaVbeta3 integrin regulates macrophage inflammatory responses via PI3
      kinase/Akt-dependent NF-kappaB activation.
AB  - Controlling macrophage responses to pathogenic stimuli is critical for prevention
      of and recovery from the inflammatory state associated with the pathogenesis of
      many diseases. The adhesion receptor alphaVbeta3 integrin is thought to be an
      important receptor that regulates macrophage differentiation and macrophage
      responses to external signaling, but it has not been previously identified as a
      contributor to macrophage-related inflammation. Using an in vitro model of human
      blood monocytes (Mo) and monocyte-derived macrophages (MDMs) we demonstrate that
      alphaVbeta3 ligation results in sustained increases of the transcription factor
      NF-kappaB DNA-binding activity, as compared with control isotype-matched IgG(1).
      Activation of NF-kappaB parallels the increase of NF-kappaB-dependent pro
      inflammatory cytokine mRNA expression in MDMs isolated from individual donors,
      for example, TNF-alpha (8- to 28-fold), IL-1beta (15- to 30-fold), IL-6 (2- to 4
      fold), and IL-8 (5- to 15-fold) whereas there is more than a 10-fold decrease in
      IL-10 mRNA level occurs. Upon ligation of the alphaVbeta3 receptor, treatment
      with TNF-alpha (10 ng/ml) or LPS (200 ng/ml, 1,000 EU) results in the enhanced
      and synergistic activation of NF-kappaB and LPS-induced TNF-alpha secretion. As
      additional controls, an inhibitor of alphaVbeta3 integrin, cyclic RGD (10 ug/ml;
      IC(50) = 7.6 uM), attenuates the effects of alphaVbeta3 ligation, and the natural
      ligand of alphaVbeta3 integrin, vitronectin, reproduces the effects of
      alphaVbeta3 activation by an immobilizing anti-alphaVbeta3 integrin mAb. We
      hypothesize that alphaVbeta3 activation can maintain chronic inflammatory
      processes in pathological conditions and that the loss of alphaVbeta3 ligation
      will allow macrophages to escape from the inflammatory state.

PMID- 20672331
TI  - 'Diffuse skin browning' in 1-MCP-treated apples: etiology and systems of control.
AB  - BACKGROUND: 'Diffuse skin browning' (DSB) is a physiological disorder that
      affects Golden Delicious apples treated with 1-methylcyclopropene (1-MCP).
      Although a very high incidence is found, very little is known about the etiology
      of this disorder. This study aims to provide an understanding of the causes of
      this disorder and prevent it. RESULTS: A very high incidence of DSB was found in
      1-MCP-treated apples independent of the location of the orchard. Similar to
      superficial scald, harvest maturity determines the DSB incidence, with the more
      mature fruit being less sensitive. The 1-MCP dose (156 nL L(-1) or 625 nL L(-1))
      and the temperature at which the 1-MCP treatment was applied (0.5 or 20  degrees
      C) did not affect the incidence of DSB. Diphenylamine (DPA) treatment did not
      prevent DSB, contrary to superficial scald. Additionally, controlled atmosphere
      storage only partially reduced the incidence of DSB, whereas progressive cooling
      strategies completely inhibited DSB occurrence. A direct correlation was found
      between the sensitivity of the Golden Delicious clone to russeting and its
      sensitivity to develop DSB during storage. CONCLUSION: Our results indicated that
      DSB and superficial scald are two different disorders involving different
      oxidative processes. DSB can be prevented by progressive cooling and selection of
      russeting-resistant clones.

PMID- 20672332
TI  - Enhancement of antimicrobial and antimutagenic activities of Korean barberry
      (Berberis koreana Palib.) by the combined process of high-pressure extraction
      with probiotic fermentation.
AB  - BACKGROUND: To evaluate the combined effects of high pressure extraction (HPE)
      and probiotic fermentation on the antimicrobial and antimutagenic activities,
      Berberis koreana was subjected to 500 MPa for 30 min and then fermented with
      Bifidobacterium longum B6 (HPE-BLF) and Lactobacillus paracasei (HPE-LPF) at 37 
      degrees C for 6 days. RESULTS: The phenol content was significantly increased to
      228 mg GAE g(-1) by the HPE compared to the conventional extraction (CE, 188 mg
      GAE g(-1)). The HPE-BLF and HPE-LPF showed the highest antimicrobial activity
      (MIC < 4 mg mL(-1)) against beta-lactam antibiotic sensitive and resistant
      Staphylococcus aureus. No significant mutagenic effect was observed for CE, HPE,
      HPE-BLF, and HPE-LPF extracts. The highest antimutagenic activities against frame
      shift mutant Salmonella typhimurium were observed at the HPE-LPF (82%), followed
      by the HPE-BLF (77%). CONCLUSION: The combined HPE and fermentation process could
      be used as an alternative extraction method for improving the extraction efficacy
      of medicinal plants. The results will provide pharmaceutically useful information
      and potential direction for finding new drug sources from medicinal plants.

PMID- 20672333
TI  - Effects of four host plants on susceptibility of Spodoptera litura (Lepidoptera:
      Noctuidae) larvae to five insecticides and activities of detoxification
      esterases.
AB  - BACKGROUND: The tobacco cutworm, Spodoptera litura (F.), is one of the most
      destructive polyphagous pests worldwide. The susceptibility of S. litura larvae
      reared on tobacco, Chinese cabbage, cowpea and sweet potato to phoxim,
      chlorfenapyr, methomyl, fenvalerate and emamectin benzoate under laboratory
      conditions was determined. RESULTS: Spodoptera litura larvae reared on tobacco
      were most tolerant to all insecticides, whereas those that fed on sweet potato
      were most susceptible. When larvae were reared on each host plant for three
      generations, the susceptibilities to phoxim of larvae that fed on Chinese cabbage
      and cowpea were similar, whereas the susceptibility of larvae that fed on sweet
      potato decreased by the third generation, and on tobacco the susceptibility
      decreased in each consecutive generation. When nicotine was added to their diet
      for three consecutive generations, the tolerance of larvae to phoxim increased
      twofold, and to emamectin benzoate 3.1-fold, but the tolerance of larvae to
      fenvalerate and chlorfenapyr did not change. The acetylcholinesterase activities
      of the larvae that fed on sweet potato and cowpea were greater than the
      activities of those that fed on Chinese cabbage and tobacco. In contrast, the
      carboxylesterase activities of the larvae that fed on tobacco and Chinese cabbage
      were greater than the activities of those that fed on sweet potato and cowpea.
      The glutathione S-transferase activities of larvae were highest when they fed on
      tobacco, followed by Chinese cabbage and cowpea, and the lowest activities were
      observed when larvae fed on sweet potato. CONCLUSION: Feeding on tobacco or with
      nicotine added to the diet, the larvae became more tolerant to insecticides,
      especially to phoxim and emamectin benzoate.

PMID- 20672334
TI  - Surface treatments and coatings to maintain fresh-cut mango quality in storage.
AB  - BACKGROUND: Edible coatings may extend fresh-cut fruit storage by preventing
      moisture loss and decreasing gas exchange. This study evaluated the effect of an
      antibrowning dip (calcium ascorbate, citric acid and N-acetyl-L-cysteine),
      followed or not with carboxymethylcellulose (CMC) or carrageenan coatings on
      quality of fresh-cut mangoes stored at 5  degrees C for up to 20 days. A fourth
      treatment, only used in one of four experiments, consisted of chitosan.
      Treatments were applied on 'Tommy Atkins', 'Kent' and 'Keitt' mangoes harvested
      from Homestead (FL), and on imported store-bought mangoes. RESULTS: The
      antibrowning dips maintained the best visual quality during storage for all
      cultivars, as indicated by higher b*, hue and L*. The CMC coating maintained
      similar visual quality, but carrageenan or chitosan decreased L* and b*. The
      antibrowning dip containing calcium ascorbate reduced firmness loss on cut pieces
      of 'Keitt', 'Kent' and store-bought mangoes. The antibrowning treatment
      maintained higher titratable acidity for 'Kent' and 'Keitt', resulting in lower
      sensory sweetness. CONCLUSION: This study with repeated experiments showed that
      calcium ascorbate with citric acid and N-acetyl-L-cysteine maintained cut mango
      slices attractiveness in storage by keeping light color in both varieties. The
      addition of a polysaccharide coating did not consistently improve quality.

PMID- 20672335
TI  - Analysis of green kiwi fruit (Actinidia deliciosa cv. Hayward) proteinases by two
      dimensional zymography and direct identification of zymographic spots by mass
      spectrometry.
AB  - BACKGROUND: Proteinases present in kiwi fruits are potentially allergenic enzymes
      belonging to the papain family of cysteine proteinases. Actinidin is a prominent
      kiwi enzyme. The study of kiwi proteinases is important for the follow-up of
      fruit maturation, a deeper insight in the allergenic properties of individual
      proteins, and the application of kiwi proteinases for meat tenderisation and
      other industrial purposes. RESULTS: Kiwi crude extracts were analysed by two
      dimensional zymography on gelatin-containing gels. The digestion by the
      reactivated proteolytic enzymes after electrophoresis resulted in insights into
      kiwi proteinases. A mixture of several enzyme isotypes with the same pI but
      different molecular mass was observed. Clear spots, corresponding to the
      proteolytic activities, were excised, digested with trypsin, and submitted to
      MALDI-ToF mass spectrometry for protein identification. The most representative
      enzyme was actinidin. CONCLUSIONS: The innovative achievements of the present
      study are the: (1) two-dimensional zymographic map of kiwi gelatinases without
      the need for extensive purification; and (2) direct identification of proteinase
      isotypes by means of direct MALDI-ToF MS analysis of the zymographic spots.

PMID- 20672336
TI  - Corrosion inhibition with different protective layers in tinplate cans for food
      preservation.
AB  - BACKGROUND: In this work the influence of essential onion oil (EOO) on the
      protection of tinplates was compared with dioctyl sebacate oil (DOS) and epoxy
      phenolic lacquers, which are frequently used in the food canning industry.
      RESULTS: When EOO as the protective layer instead of DOS oil was used, tinplate
      porosity, measured electrochemically (7.58 +/- 1.97 uA cm(-2) and 23.0 +/- 1.3 uA
      cm(-2), respectively), and iron coating mass, calculated from AAS data (1.52 +/-
      0.15 mg m(-2) and 3.14 +/- 0.42, respectively), was much lower indicating better
      corrosion protection. At higher storing temperature (36  degrees C) the addition
      of EOO to canned tomato puree enhanced the formation of hydrogen with time. The
      increasing volume fraction of H(2) (from 34.0 to 90.9% for cans without nitrates,
      and from 33.8 to 89.2% for cans with nitrates) is an indicator that corrosion
      takes place. CONCLUSION: As the use of EOO improves the protection of tinplate
      compared with DOS oil, and is almost as effective as epoxy phenolic lacquer, the
      addition of EOO can be recommended due to lower cost of canned food production
      and enhanced organoleptic properties, but the storage temperature has to be lower
      then 36  degrees C.

PMID- 20672337
TI  - A combination of hot air treatment and nano-packing reduces fruit decay and
      maintains quality in postharvest Chinese bayberries.
AB  - BACKGROUND: Chinese bayberry is susceptible to microbial decay during postharvest
      handling and storage. To search for effective alternatives to currently used
      fungicides for disease control, the efficacy of hot air (HA) treatment at 48 
      degrees C for 3 h alone or in combination with nano-packing (NP) containing nano
      TiO(2) and nano-Ag in controlling green mould decay caused by Penicillium
      citrinum and natural decay, and their effects on fruit quality in harvested
      Chinese bayberries were investigated in this study. RESULTS: The combined
      treatment of HA and NP resulted in a remarkably improved control of green mould
      and natural decay in Chinese bayberries compared with treatment of HA or NP
      alone. The in vitro growth of P. citrinum was significantly inhibited by
      individual HA or NP. In addition, HA in combination with NP showed interactive
      effect on inhibiting fruit respiration, ethylene production and membrane lipid
      peroxidation, and maintained higher fruit firmness and DPPH radical scavenging
      activity. CONCLUSION: These results suggest that a combination of HA treatment
      and NP may be a useful technique to reduce fruit decay and maintain quality in
      Chinese bayberries during postharvest storage and retail conditions.

PMID- 20672338
TI  - Development of a new dispenser for microbiological control agents and evaluation
      of dissemination by bumblebees in greenhouse strawberries.
AB  - BACKGROUND: To date, in modern agriculture, biological control strategies are
      increasingly becoming the preferred pest management approach. However, the
      success of microbiological control agents (MCAs) largely depends on efficient
      dissemination into the crop. The pollinator-and-vector technology employs
      pollinating insects like bees for a better dissemination. In this study, a new
      dispenser for bumblebee workers of Bombus terrestris L. was developed. Binab-T
      vector and Prestop-Mix were used as two typical MCA products for dissemination.
      RESULTS: In a first series of experiments in the laboratory for optimisation, the
      newly developed dispenser was a two-way type dispenser, 20 cm long, with two
      rectangular compartments and different entrance and exit holes. In addition, the
      amounts of MCA loaded on the workers were 10 times higher with the new dispenser
      as compared with the side-by-side passageway (SSP) dispenser. Typically, the
      highest amounts were recovered from the thorax and legs of the workers. In a
      second series of experiments under greenhouse conditions with the use of queen
      right B. terrestris hives, successful dissemination in strawberry flowers was
      obtained at different distances from the hive (0-8 m, 8-18 m and 18-21 m), and
      the workers inoculated the first, second and third flowers that were
      consecutively visited. In addition, the new dispenser caused no adverse effects
      on worker foraging intensity, whereas a dramatic reduction was scored with an SSP
      dispenser. Finally, the data suggested that it is necessary to refill the newly
      developed dispenser at 3 day intervals. CONCLUSIONS: The results demonstrated
      that, with the use of the newly developed dispenser, bumblebee workers carried
      high amounts of MCA, and this resulted in a successful dissemination of MCA into
      strawberry flowers.

PMID- 20672339
TI  - Is Apis mellifera more sensitive to insecticides than other insects?
AB  - BACKGROUND: Honey bees (Apis mellifera L.) are among the most important
      pollinators in natural and agricultural settings. They commonly encounter
      insecticides, and the effects of insecticides on honey bees have been frequently
      noted. It has been suggested that honey bees may be (as a species) uniquely
      sensitive to insecticides, although no comparative toxicology study has been
      undertaken to examine this claim. An extensive literature review was conducted,
      using data in which adult insects were topically treated with insecticides. The
      goal of this review was to summarize insecticide toxicity data between A.
      mellifera and other insects to determine the relative sensitivity of honey bees
      to insecticides. RESULTS: It was found that, in general, honey bees were no more
      sensitive than other insect species across the 62 insecticides examined. In
      addition, honey bees were not more sensitive to any of the six classes of
      insecticides (carbamates, nicotinoids, organochlorines, organophosphates,
      pyrethroids and miscellaneous) examined. CONCLUSIONS: While honey bees can be
      sensitive to individual insecticides, they are not a highly sensitive species to
      insecticides overall, or even to specific classes of insecticides. However, all
      pesticides should be used in a way that minimizes honey bee exposure, so as to
      minimize possible declines in the number of bees and/or honey contamination.

PMID- 20672340
TI  - Comparison of the activity of non-steroidal ecdysone agonists between dipteran
      and lepidopteran insects, using cell-based EcR reporter assays.
AB  - BACKGROUND: Diacylhydrazine (DAH) analogues have been developed successfully as a
      new group of insect growth regulators, called ecdysone agonists or moulting
      accelerating compounds. These DAHs have been shown to manifest their toxicity via
      interaction with the ecdysone receptor (EcR) in susceptible insects, as does the
      natural insect moulting hormone 20-hydroxyecdysone (20E). A notable feature is
      their high activity and specificity, particularly against lepidopteran insects,
      raising the question as to whether non-lepidopteran-specific analogues can be
      isolated. However, for the discovery of ecdysone agonists that target other
      important insect groups such as Diptera, efficient screening systems that are
      based on the activation of the EcR are needed. RESULTS: In this study, a dipteran
      specific reporter-based screening system with transfected S2 cells of Drosophila
      melanogaster Meig. was developed in order to discover and evaluate compounds that
      have ecdysone agonistic or antagonistic activity. A library of non-steroidal
      ecdysone agonists containing different mother structures with DAH and other
      related analogues such as acylaminoketone (AAK) and tetrahydroquinoline (THQ) was
      tested. None of the compounds tested was as active as 20E. This is in contrast to
      the very high activity of several DAH and AAK congeners in lepidopteran cells
      (Bombyx mori L.-derived Bm5 cells). The latter agrees with a successful docking
      of a DAH, tebufenozide, in the binding pocket of the lepidopteran EcR (B. mori),
      while this was not the case with the dipteran EcR (D. melanogaster). Of note was
      the identification of two THQ compounds with activity in S2 but not in Bm5 cells.
      Although marked differences in activity exist with respect to the activation of
      EcR between dipterans and lepidopterans, there exists a positive correlation (R =
      0.724) between the pLC(50) values in S2 and Bm5 cells. In addition, it was found
      through protein modelling that a second lobe was present in the ligand-binding
      pocket of lepidopteran BmEcR but was lacking in the dipteran DmEcR protein,
      suggesting that this difference in structure of the binding pocket is a major
      factor for preferential activation of the lepidopteran over the dipteran
      receptors by DAH ligands. CONCLUSIONS: The present study confirmed the marked
      specificity of DAH and AAK analogues towards EcRs from lepidopteran insects. THQ
      compounds did not show this specificity, indicating that dipteran-specific
      ecdysone-agonist-based insecticides based on the THQ mother structure can be
      developed. The differences in activity of ecdysone agonists in dipteran and
      lepidopteran ecdysone-reporter-based screening systems are discussed.

PMID- 20672341
TI  - Variation in saponin content during the growing season of spotted medic [Medicago
      arabica (L.) Huds.].
AB  - BACKGROUND: Spotted medic [Medicago arabica (L.) Huds.] is a minor forage species
      containing saponins which are reported to be biologically active. This study
      assessed the concentration and composition pattern of spotted medic saponins
      during the growing season and at senescence. The pattern of saponins was based on
      identification and quantification of their constituent sapogenins. At senescence,
      individual saponin concentrations of aerial and subterranean plant organs were
      also determined. RESULTS: Leaf total saponin content did not vary during the
      growing season and decreased remarkably at senescence. Seven sapogenins were
      identified and quantified during the season, bayogenin and hederagenin being the
      most abundant ones throughout. Total saponin content varied among plant organs at
      senescence, with the highest concentration in roots. A variable number of
      saponins from one (in seeds) to 19 (in leaves) were quantified. A clear
      relationship between leaf concentrations of sapogenins and those of their
      derivative saponins was revealed by correlation analysis. CONCLUSION: The species
      displayed a sapogenins/saponins pattern markedly different from those of other
      perennial or annual Medicago species. Saponins of queretaroic acid and 2beta
      hydroxy queretaroic acid had no precedent in the Leguminosae. The high
      concentration of biologically active hederagenin suggested further assessment of
      possible effects on feeding animals.

PMID- 20672342
TI  - "Trousseau's disease:" a description of the Gilles de la Tourette syndrome 12
      years before 1885.
AB  - French neurologist Georges Gilles de la Tourette first described the syndrome
      which earned him eponymous fame in 1885. However, a publication dated 1873 by
      Armand Trousseau included a detailed account of what is currently know as Gilles
      de la Tourette syndrome (GTS). In Gilles de la Tourette's celebrated 1885 paper,
      there is a brief mention of the clinical picture described earlier by Trousseau,
      but Gilles de la Tourette somewhat disregarded it. We present the first English
      translation of Trousseau's description and argue that this description is more
      akin to modern conceptualization of GTS than the description of Gilles de la
      Tourette himself.

PMID- 20672343
TI  - Biochemical characterization of a bacteriocin-like inhibitory substance produced
      by Enterococcus faecium MXVK29, isolated from Mexican traditional sausage.
AB  - BACKGROUND: Enterococci are lactic acid bacteria that can produce bacteriocins,
      which may offer an additional hurdle to control the growth of food-borne
      pathogens; moreover, these bacteriocins may have great potential as natural
      biopreservatives. The aim of this work was to characterize a bacteriocin-like
      inhibitory substance (BLIS) with antilisterial activity produced by an
      enterococcal strain. RESULTS: The bacteriogenic strain was isolated from Mexican
      fermented sausages and identified as Enterococcus faecium with 99% sequence
      similarity. Maximal activity was detected at 16 h, where bacterial growth was in
      middle of the stationary phase. The producer strain was not inhibited by its own
      antimicrobial peptide. BLIS showed a strong anti-Listeria activity and was
      inactivated by proteinase K. Heating (121  degrees C for 15 min) induced some
      inactivation, but thermotolerance was higher at acid pH values. The yield
      obtained with a pH-mediated purification process was 32.7%, showing a band with
      an estimated molecular weight of 3.5 kDa. Automated N-terminal Edman degradation
      showed the following sequence: YYGNGVTCGSHHCSVD. CONCLUSION: Biochemical
      characteristics of BLIS produced by E. faecium MXVK29 suggested that it belongs
      to Class IIa of the Klaenhammer classification and could be considered as a
      natural food preservative, although further studies need to be performed.

PMID- 20672344
TI  - Living his writings: the example of neurologist G. Gilles de la Tourette.
AB  - Gilles de la Tourette is known for the disease which now bears his name. As one
      of the closest followers of Jean-Martin Charcot, he always remained faithful to
      his mentor's views and was one of the most vehement defenders of La Salpetriere.
      His activities in the management of hysterics and in hypnotism helped build his
      reputation during his lifetime, but are now largely forgotten. Gilles de la
      Tourette had an unusual personality, with hypomanic and histrionic traits. We
      present some ignored aspects of his life based on the discovery of personal
      letters which illuminate the hidden side of this famous neurologist.

PMID- 20672345
TI  - Greeter's cramp.

PMID- 20672346
TI  - The visceral yolk sac endoderm provides for absorption of nutrients to the embryo
      during neurulation.
AB  - Neural tube defects (NTDs) represent some of the most common congenital
      malformations in humans. The causes of NTDs are complex with both genetic and
      environmental contributing factors. Periconception nutrition is an important
      environmental factor influencing the penetrance of NTDs. NTDs arise from failure
      to close the neural tube completely during development, an event that occurs
      before establishment of the chorioallantoic placenta. During neurulation,
      nutrients are absorbed by histotrophic mechanisms and absorbed by endocytosis in
      the endoderm-derived cell layer of the visceral yolk sac (VYS). Here we review
      the histotrophic mechanisms by which nutrients are delivered to the human embryo
      during this critical time period. Because more detailed studies on the molecular
      mechanisms regulating uptake of nutrients have been performed using rodent
      models, most importantly mouse and rat models, we will also review nutrient
      uptake in these model organisms to set the stage for presentation of experimental
      data that have provided valuable information about how nutrients are delivered to
      the neurulating embryo.

PMID- 20672347
TI  - Decongestant use during pregnancy and its association with preterm delivery.
AB  - BACKGROUND: Despite the frequent intake of decongestants during pregnancy, only
      one study to date has evaluated the association of decongestants with preterm
      delivery, and it identified a reduced risk. We examined this association in more
      detail. METHODS: Using a population-based random sample of 3271 Massachusetts
      live-born births without major malformations, we categorized decongestant
      exposure according to timing, frequency of use, route, and indication. Preterm
      birth was defined as a gestational age of <37 completed weeks. We estimated
      hazard ratios and examined confounding by indication by examining various strata
      of women and through multivariate adjustment. RESULTS: Compared to nonexposed
      women, those who took decongestants during the second or third trimester only
      were less likely to experience preterm delivery (HR, 0.42; 95% CI, 0.21-0.84).
      This association was observed only for women without preeclampsia. CONCLUSIONS: A
      protective association between decongestant use and preterm delivery has now been
      observed in two studies; however, the possibility of confounding by underlying
      condition remains.

PMID- 20672348
TI  - Reduction in cadmium-induced toxicity and c-Jun N-terminal kinase activation by
      glutathione in cultured mouse embryonic cells.
AB  - INTRODUCTION: Cadmium (Cd(2+)) induces limb defects and other malformations in
      experimental animals. However, the mechanisms of the developmental toxicity of
      this metal are not fully understood. The ubiquitous intracellular tripeptide
      glutathione (GSH) protects nonembryonic cells from Cd(2+)-induced cell death and
      is essential for normal embryonic development. We predicted that pretreatment
      with GSH would prevent cytotoxicity in cultured mouse embryonic limb bud cells
      exposed to Cd(2+). Additionally, it was expected that GSH pretreatment would
      prevent the Cd(2+)-induced activation of the signaling molecule c-Jun N-terminal
      kinase (JNK), which becomes phosphorylated upon exposure to Cd(2+). METHODS:
      Primary micromass cultures of limb bud cells obtained from organogenesis-stage
      mouse embryos were treated with either Cd(2+) or GSH alone, or both Cd(2+) and
      GSH. Treatment with GSH commenced 4 hr prior to Cd(2+) treatment. RESULTS: Cell
      proliferation was inhibited by approximately 50% after exposure to 4 MUM Cd(2+)
      for 5 days. Cd(2+) treatment also resulted in a dose-dependent increase in the
      intracellular GSH content as measured after 5 days of exposure. Pretreatment with
      4 mM GSH for 4 hr prevented the Cd(2+)-induced inhibition of cell proliferation
      and differentiation and also inhibited a threefold activation of JNK induced by 4
      MUM Cd(2+) after 24 and 48 hr of exposure. CONCLUSION: Exogenous GSH protects
      cultured embryonic limb bud cells from Cd(2+)-induced inhibition of cell
      proliferation and differentiation, which is associated with the activation of
      JNK.

PMID- 20672349
TI  - Evidence for linkage of the bladder exstrophy-epispadias complex on chromosome
      4q31.21-22 and 19q13.31-41 from a consanguineous Iranian family.
AB  - BACKGROUND: The bladder exstrophy-epispadias complex (BEEC) is a spectrum of
      anomalies involving the abdominal wall, pelvis, urinary tract, genitalia, and,
      occasionally, the spine and anus. Although BEEC typically occurs sporadically,
      families with two or more affected members have been reported. The present
      authors previously conducted a genome-wide linkage analysis in two multiply
      affected (multiplex) families (one of German and one of Spanish origin), which
      revealed several chromosomal regions compatible with linkage. In the present
      study, genome-wide linkage analysis was performed in a recently reported
      consanguineous Iranian multiplex family with an affected sibling pair: a female
      with epispadias and a male with classic exstrophy of the bladder. METHODS: The
      Affymetrix 250K Sty chip (238,304 single nucleotide polymorphisms) was used to
      genotype the parents and four children, including the two affected siblings.
      Parametric and nonparametric linkage analyses were performed. RESULTS: Parametric
      linkage analysis under a recessive model with complete penetrance identified
      seven loci with LOD scores >1.6 (1p33, 4q31.21-22, 9q22.33, 12q13.13-2, 13q12.12
      13, 18q23, and 19q13.31-41). These results were supported by nonparametric
      linkage analysis. Haplotype analysis showed that the affected individuals were
      homozygous identical by descent for all seven regions. Two of these regions
      overlapped with regions observed previously in the Spanish family -one on
      chromosome 4q31.21-22, and the other on chromosome 19q13.31-41. CONCLUSION: These
      results suggest that chromosomal regions 4q31.21-22 and 19q13.31-41 are likely to
      harbor genes for an autosomal recessive form of BEEC.

PMID- 20672350
TI  - Genetic variants in COL2A1, COL11A2, and IRF6 contribute risk to nonsyndromic
      cleft palate.
AB  - BACKGROUND: Orofacial clefts are among the most common birth defects with a
      strong genetic component. Nonsyndromic cleft palate (NSCP) is a complex
      malformation determined by the interaction between multiple genes and
      environmental risk factors. METHODS: We conducted a case-control association
      study to investigate the role of 40 candidate genes in predisposition to
      orofacial clefting. Five hundred ninety-one haplotype tagging single nucleotide
      polymorphism (tagSNPs) were genotyped in a clefting sample from the Baltic
      region, composed of 104 patients with nonsyndromic cleft palate and 606 controls
      from an Estonian, Latvian, and Lithuanian population. RESULTS: In case-control
      comparisons, the minor alleles of IRF6 rs17389541 (p = 5.45 * 10(-4)) and COL2A1
      rs1793949 (p = 7.26 * 10(-4)) were associated with increased risk of NSCP.
      Multiple haplotypes in COL2A1 and COL11A2 and haplotypes in WNT3, FGFR1, and
      CLPTM1were associated with NSCP. The strongest associations were found for IRF6
      haplotype rs17389541/rs9430018 GT (p = 2.23 * 10(-4)) and COL2A1 haplotype
      rs12822608/rs6823 GC (p = 3.68 * 10(-4)). The strongest epistatic interactions
      were observed between MSX1 and BMP2, FGF1 and PVRL2, and COL2A1 and FGF2 genes.
      CONCLUSIONS: This study provides for the first time evidence of the implication
      of IRF6, COL2A1, and WNT3 in the occurrence of NSCP. It is likely that variation
      in cartilage collagen II and XI genes, IRF6, and the Wnt and FGF signaling
      pathway genes contributes susceptibility to nonsyndromic cleft palate in
      Northeastern European populations.

PMID- 20672351
TI  - Mortality among infants with birth defects: Joint effects of size at birth,
      gestational age, and maternal race/ethnicity.
AB  - BACKGROUND: We examined the separate and joint effects of gestational age, size
      at birth and maternal race/ethnicity on early childhood survival among 48,391
      singleton infants with major birth defects. METHODS: Texas Birth Defects Registry
      data were linked to death records and the National Death Index to ascertain
      deaths. Gestational age categories were preterm or term birth; size at birth
      included small for gestational age (SGA), appropriate for gestational age (AGA),
      and large for gestational age (LGA). Kaplan-Meier survival estimates were
      calculated, and Cox-proportional hazards models were used to calculate hazard
      ratios (HR) and 95% confidence intervals (CI) to determine risk of death after
      adjusting for covariates. RESULTS: Overall, relative to non-Hispanic (NH) 
      whites, NH-blacks, and Hispanics had a 51 and 10% greater risk of death during
      early childhood, respectively. Compared to NH-whites born term and AGA (survival
      = 97%), Hispanic children born SGA and preterm had the greatest risk of death
      (HR(a) = 6.1; 95% CI, 5.2, 7.2) and the lowest early childhood survival (76%),
      followed by SGA preterm NH-blacks (HR(a) = 4.8; 95% CI, 3.6, 6.5; survival = 81%)
      and SGA preterm NH-whites (HR(a) = 4.5; 95% CI, 3.7, 5.6; survival = 83%).
      Children born LGA at term had no increased risk of mortality regardless of
      maternal race/ethnicity. CONCLUSIONS: The joint effect of gestational age and
      size at birth had greatest impact on childhood mortality. Additional population
      based studies are needed to better understand causes of racial/ethnic disparities
      in mortality among children with birth defects.

PMID- 20672352
TI  - Midterm outcomes in patients with intermediate-sized hepatocellular carcinoma: a
      randomized controlled trial for determining the efficacy of radiofrequency
      ablation combined with transcatheter arterial chemoembolization.
AB  - BACKGROUND: To improve the efficacy of radiofrequency ablation (RFA) for the
      treatment of intermediate-sized hepatocellular carcinomas (HCCs), the authors
      compared RFA combined with transcatheter arterial chemoembolization (TACE) to RFA
      alone. METHODS: The authors randomly assigned 37 patients with solitary HCCs
      (diameter, 3.1-5.0 cm in the greatest dimension) to 2 groups: the TACE-RFA group,
      in which the patients received TACE followed by RFA on the same day, and the RFA
      group, in which the patients received only RFA. RESULTS: Technical success was
      achieved after 1.4+/-0.5 RFA sessions in the RFA group and after 1.1+/-0.2 RFA
      sessions in the TACE-RFA group (P<.01). The mean diameters of the longer and
      shorter axes of the RFA-induced ablated areas were 50+/-8.0 mm and 41+/-7.1 mm,
      respectively, in the RFA group and 58+/-13.2 mm and 50+/-11.3 mm, respectively,
      in the TACE-RFA group; the mean diameters of the shorter axes were significantly
      different (P=.012). The rates of local tumor progression at the end of the third
      year in the RFA and TACE-RFA groups were 39% and 6%, respectively (P=.012). The 3
      year survival rates of the patients in the RFA and TACE-RFA groups were 80% and
      93%, respectively (P=.369). CONCLUSIONS: In patients with intermediate-sized
      HCCs, RFA combined with TACE is more effective than RFA alone for extending the
      ablated area in fewer treatment sessions and for decreasing the local tumor
      progression rate.

PMID- 20672353
TI  - Osteosarcoma in very young children: experience of the Cooperative Osteosarcoma
      Study Group.
AB  - BACKGROUND: This study was conducted to investigate presentation, treatment, and
      outcome in very young children with osteosarcoma. METHODS: The authors
      retrospectively analyzed the data of 2706 consecutive COSS patients with newly
      diagnosed osteosarcoma and identified 28 (1.0%) patients aged younger than 5
      years at diagnosis. Demographic, diagnostic, tumor, treatment-related variables,
      response, and survival data were analyzed. RESULTS: Of the 28 preschoolers, 27
      presented with high-grade central osteosarcoma of an extremity, and 1 had a
      secondary osteosarcoma of the orbit. This analysis focused on the 27 patients
      with extremity tumors. The size of the primary was large (>=one-third of the
      involved bone) in 20 of 27 patients. Primary metastases were detected in 4 of 27
      children. All patients received multiagent chemotherapy, and 11 of 18 analyzed
      tumors responded well (>90% necrosis) to neoadjuvant chemotherapy. Limb-sparing
      surgery was performed in 9 cases, ablative procedures were performed in 15, and,
      in 3 cases, no local surgery was performed. With a median follow-up of 4 years
      (6.2 years for survivors), 13 patients were alive. Four patients never achieved a
      complete remission, and 11 developed recurrences; 14 of these 15 patients died.
      Five-year overall and event-free survival probabilities were 51% (standard error
      of the mean [SE], 10%) and 48% (SE, 10%). Better survival was correlated with
      good response to chemotherapy and later time period of diagnosis. CONCLUSIONS:
      Osteosarcoma is extremely rare in preschool children. These patients often have
      large tumors that may require mutilating resections. Prognosis is in the range of
      that reported for older patients.

PMID- 20672354
TI  - Cancer incidence in the multicenter AIDS Cohort Study before and during the HAART
      era: 1984 to 2007.
AB  - BACKGROUND: The incidence of Kaposi sarcoma (KS) and non-Hodgkin lymphoma (NHL)
      among human immunodeficiency virus (HIV)-infected individuals declined after the
      introduction of highly active antiretroviral therapy (HAART) in the mid-1990s,
      but the cancer risk associated with HIV infection during the HAART era remains to
      be clarified. METHODS: Cancer incidence among HIV-infected and HIV-uninfected
      participants in the Multicenter AIDS (acquired immunodeficiency syndrome) Cohort
      Study (MACS) between 1984 and 2007 was compared with the expected incidence using
      US population-based data from the Surveillance, Epidemiology, and End Results
      (SEER) program. Age- and race-adjusted cancer incidence rates were also compared
      HIV by status and over time within the MACS. Exact statistical methods were used
      for all analyses. RESULTS: A total of 933 incident cancers were observed during
      77,320 person-years of follow-up. Compared with SEER, MACS HIV-infected men had
      significantly (P<.05) elevated rates of KS (standardized incidence ratio [SIR],
      139.10), NHL (SIR, 36.80), Hodgkin lymphoma (HL)(SIR, 7.30), and anal cancer
      (SIR, 25.71). Within MACS, HIV infection was found to be independently associated
      with each of these cancers across the entire follow-up period, and KS (incidence
      rate ratio [IRR], 54.93), NHL (IRR, 11.18), and anal cancer (IRR, 18.50) were
      each found to be significantly elevated among HIV-infected men during the HAART
      era. Among these men, the incidence of KS and NHL declined (IRR, 0.13 and 0.23,
      respectively), the incidence of anal cancer increased (IRR, 5.84), and the
      incidence of HL remained statistically unchanged (IRR, 0.75) from the pre-HAART
      to the HAART era. CONCLUSIONS: Cancer risk remains elevated among HIV-infected
      men who have sex with men, highlighting the continuing need for appropriate
      cancer screening in this population.

PMID- 20672355
TI  - Methylenetetrahydrofolate reductase gene polymorphisms and neural tube defects
      epidemiology in the Slovak population.
AB  - BACKGROUND: Folate deficiency is a known factor contributing to the formation of
      neural tube defects (NTDs). Many folate metabolism gene variants have been
      investigated, but only a few substantial associations have been established, the
      C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene being
      one of the most significant. METHODS: We determine the MTHFR C677T and A1298C
      genotypes in 93 Slovak NTD patients and 290 control newborns with respect to sex
      and ethnicity. Furthermore, we summarize current data on the incidence and types
      of NTDs in Slovakia. RESULTS: The Slovak population frequencies of T allele and
      TT genotype of the C677T MTHFR gene polymorphism were 0.25 and 6.9%,
      respectively; similarly, those of the C allele and CC genotype of the A1298C
      polymorphism were 0.35 and 13.8%, respectively. No differences between the sexes
      and within ethnic groups were observed. In NTD patients, genotype analysis of the
      C677T polymorphism revealed 0.29 and 9.8% for T allele and TT genotype
      frequencies, respectively (p = 0.26; OR, 1.23; 95% CI, 0.84-1.81; resp. p = 0.36;
      OR, 1.46; 95% CI, 0.56-3.52) compared to the controls. The frequencies of C
      allele and CC genotype of A1298C polymorphism were 0.34 and 6.5%, respectively (p
      = 0.81; OR, 0.96; 95% CI, 0.66-1.38; resp. p = 0.06; OR, 0.44; 95% CI, 0.15
      1.09). There were also no sex-related differences in genotypes distribution in
      NTD patients. CONCLUSIONS: No significant associations between the C677T and
      A1298C MTHFR gene polymorphisms and NTDs and no differences between the two main
      ethnic groups (white-Caucasians, Roma) were found in Slovakia. The total
      incidence of NTDs in Slovakia is, according to the official sources, 0.53/1000,
      and the incidence among liveborn newborns is 0.28/1000.

PMID- 20672356
TI  - Quality of cancer care among foreign-born and US-born patients with lung or
      colorectal cancer.
AB  - BACKGROUND: Disparities in care have been documented for foreign-born cancer
      patients in the United States. However, few data are available regarding patients
      with lung and colorectal cancer. In the current study, the authors assessed
      whether patient-reported quality and receipt of recommended care differed between
      US-born and foreign-born cancer patients. METHODS: The authors collected surveys
      and medical records for a population-based cohort including white, Hispanic, and
      Asian adults (2205 US-born and 890 foreign-born individuals) with lung or
      colorectal cancer diagnosed in California from 2003 through 2005. Logistic
      regression was used to assess the association between nativity and patient
      reported quality of care and receipt of recommended treatments (adjuvant
      chemotherapy for stage III colon cancer, adjuvant chemotherapy and radiotherapy
      for stage II/III rectal cancer, and curative surgery for stage I/II nonsmall cell
      lung cancer). The authors also assessed whether language explained any
      differences in care by nativity. RESULTS: Overall, 46% of patients reported
      excellent care, but foreign-born patients were less likely than US-born patients
      to report excellent quality of care (adjusted odds ratio [AOR], 0.80; 95%
      confidence interval [95% CI], 0.65-1.00), a difference partly explained by the
      language of the survey, an indicator of English proficiency. Rates of recommended
      therapies ranged from 64% to 85%; foreign-born patients were less likely to
      receive chemotherapy and radiotherapy for stage II/III rectal cancer (AOR, 0.35;
      95% CI, 0.12-0.99). Rates of other treatments did not differ significantly by
      nativity. CONCLUSIONS: Foreign-born cancer patients reported lower quality of
      care and were less likely to receive some cancer therapies than patients born in
      the Unites States. Better coordination of care and communication regarding cancer
      treatments and expanded use of interpreters may lessen these disparities.

PMID- 20672357
TI  - Dysembryoplastic neuroepithelial tumors and cognitive outcome: cure at a price?
AB  - BACKGROUND: Dysembryoplastic neuroepithelial tumors (DNETs) are benign
      glioneuronal tumors that occur in children. These tumors are characterized by
      seizures, lack of neurologic deficits, and a seemingly benign course after
      resection. METHODS: A retrospective review was conducted of data relating to 11
      children diagnosed with DNETs between January 1988 and December 2007 at St. Jude
      Children's Research Hospital. This report documented the clinical features,
      neurocognitive function, and treatment outcomes in this institutional series.
      RESULTS: The patient cohort included 8 boys and 3 girls (median age at diagnosis,
      10 years); all patients presented with seizures: 4 complex partial, 3 generalized
      tonic-clonic, 2 absence, 1 partial simple, and 1 not classified. Of the 11
      patients, 1 died of cardiac fibrosis, and tumors recurred or progressed in 4
      (36%) patients. Seizure control was achieved in all patients but 1. Of the 9
      patients who completed neuropsychologic testing, only 3 (33%) functioned at or
      above the expected level of same-age peers. CONCLUSIONS: The high recurrence and
      progression rates of DNETs and the high rate of abnormal neurocognitive test
      results noted in the current study highlight the need for regular follow-up and
      appropriate academic counseling of children with these tumors.

PMID- 20672358
TI  - Maintenance therapy with low-dose azacitidine after allogeneic hematopoietic stem
      cell transplantation for recurrent acute myelogenous leukemia or myelodysplastic
      syndrome: a dose and schedule finding study.
AB  - BACKGROUND: Recurrence is a major cause of treatment failure after allogeneic
      transplantation for acute myelogenous leukemia (AML) and myelodysplastic syndrome
      (MDS), and treatment options are very limited. Azacitidine is a DNA
      methyltransferase inhibitor with activity in myeloid disease. The authors
      hypothesized that low-dose azacitidine administered after transplant would reduce
      recurrence rates, and conducted a study to determine a safe dose/schedule
      combination. METHODS: Forty-five high-risk patients were treated. Median age was
      60 years; median number of comorbidities was 3; 67% were not in remission. By
      using a Bayesian adaptive method to determine the best dose/schedule combination
      based on time to toxicity, the authors investigated combinations of 5 daily
      azacitidine doses, 8, 16, 24, 32, and 40 mg/m2, and 4 schedules: 1, 2, 3, or 4
      cycles, each with 5 days of drug and 25 days of rest. Cycle 1 started on Day +40.
      RESULTS: Reversible thrombocytopenia was the dose-limiting toxicity. The optimal
      combination was 32 mg/m2 given for 4 cycles. Median follow-up was 20.5 months.
      One-year event-free and overall survival were 58% and 77%, justifying further
      studies to estimate long-term clinical benefit. No dose significantly affected
      DNA global methylation. CONCLUSIONS: Azacitidine at 32 mg/m2 given for 5 days is
      safe and can be administered after allogeneic transplant for at least 4 cycles to
      heavily pretreated AML/MDS patients. The trial also suggested that this treatment
      may prolong event-free and overall survival, and that more cycles may be
      associated with greater benefit.

PMID- 20672359
TI  - Do risk factors for persistent asthma modify lung function in infants and young
      children with recurrent wheeze?
AB  - SUMMARY BACKGROUND: There is very limited information on how the risk of
      persistent asthma in recurrent wheezing (RW) infants modifies their lung function
      early in life. The aim of this study is to compare lung function of RW infants
      and young children with a positive or negative asthma predictive index (API), an
      index previously used to anticipate asthma persistence into childhood and
      adolescence. METHODS: Two groups of RW infants and young children were recruited
      in two centres in Spain (Palma de Mallorca and Murcia). Lung function was
      measured according to the thoracho-abdominal compression technique (RCT), and
      values of the maximal flow at functional residual capacity (V'FRC) were expressed
      as Z-scores. Other variables included in the study, as independent factors, were:
      gender, age, length, weight, and parental smoking habits together with
      information regarding API. RESULTS: Expressed as mean +/- SD, API+ RW infants (n
      = 50; age in months 11.9 +/- 4.9) had a lower V'FRC Z-score than API- RW ones (n
      = 41; age in months 12.3 +/- 6.2; -2.01 +/- 0.79 vs. -1.64 +/- 0.77, P = 0.026,
      respectively). Centre and tobacco exposition did not have an effect on lung
      function. CONCLUSION: Among RW infants and young children, those having a
      positive API have a significant lower lung function as measured by V'FRC at an
      early age.

PMID- 20672360
TI  - Gender differences in the Scandinavian cystic fibrosis population.
AB  - AIMS: To explore whether gender differences in the Scandinavian Cystic Fibrosis
      (CF) patients exist in the areas of key clinical parameters, complications, and
      medication. METHODS: Cross-sectional data on 890 (416 female) pancreatic
      insufficient CF patients were evaluated regarding chronic infection, body mass
      index, lung function, medication, and diabetes, as well as data of Pseudomonas
      infection status, antibiotic treatment and hospitalization from 1-year follow-up.
      RESULTS: We found no differences in lung function, body mass index, or frequency
      of diabetes. The adult group consisted of more males than females (208:168). We
      found no significant difference in prevalence of chronic Pseudomonas aeruginosa
      infection, but during the follow-up the incidence of new chronic infection was
      higher in adult females (10/33 vs. 4/56). Females had higher prevalence of
      Burkholderia infection (21/416 vs. 11/474). Adult females had more days on
      intravenous antibiotics (median 39 vs. 26 days/year), and days in hospital
      (median 2 vs. 0 days/year). More adult females received inhaled and oral
      steroids. In the pediatric cohort, females were treated more often with
      macrolides as an anti-inflammatory agent. CONCLUSION: We found no gender
      difference in key clinical parameters in our CF population. However, our study
      showed a higher risk of Pseudomonas and Burkholderia infection among the female
      patients. Additionally, we found that female patients require more intensified
      treatment regarding antibiotics, macrolides, steroids and days of
      hospitalization, indicating a true female disadvantage even with modern
      aggressive treatment. The finding of more males than females in the adult
      population suggesting a male advantage, warrants a mortality study.

PMID- 20672361
TI  - Tracheal gas insufflation with partial liquid ventilation to treat LPS-induced
      acute lung injury in juvenile piglets.
AB  - OBJECTIVES: Partial liquid ventilation (PLV) with perfluorocarbons (PFC) seems
      not superior to conventional ventilation clinically. We hypothesized that a
      combination of continuous tracheal gas insufflation (TGI) with protective
      strategy of PLV (low dose of PFC, low inflation pressure, moderate inhalation of
      oxygen and moderate anesthesia) would improve cardiopulmonary function in acute
      lung injury. METHODS: Twenty-four healthy juvenile piglets were anesthetized and
      mechanically ventilated at PEEP of 2 cmH(2)O with a peak inspiratory pressure of
      10 cmH(2)O and FIO(2) of 0.4. The piglets were challenged with lipopolysaccharide
      and randomly assigned to four groups (n = 6 each): (1) mechanical ventilation
      alone (MV); (2) PLV with perfluorodecalin (10 ml/kg); (3) TGI with continuous
      airway flow 2 L/min; and (4) combination of PLV and TGI. The outcome was assessed
      functionally and histologically. RESULTS: All treatments except MV improved pH,
      PaO(2)/FIO(2), PaCO(2), ventilation efficacy index (VEI) and tidal volume. Both
      PLV-associated treatments also improved heart rate, respiratory rate, pulse
      contour cardiac output, systemic vascular resistance, dynamic lung compliance,
      mean airway resistance and mean airway pressure. The combination group resulted
      in higher PaO(2)/FIO(2), VEI and a better lung histology score than any other
      treatments. CONCLUSIONS: The new protective strategy may provide a better
      treatment for sepsis-induced acute lung injury.

PMID- 20672363
TI  - Early wheeze as reported by mothers and lung function in 4-year-olds. Prospective
      cohort study in Krakow.
AB  - SUMMARY: The purpose of the study was to check the hypothesis that early wheezing
      as reported by mothers would be associated with reduced lung function in 4-year
      olds. Study participants were recruited prenatally, as part of a prospective
      cohort study on the respiratory health of young children exposed to various
      ambient air pollutants. After delivery, infants were followed over 4 years and
      the interviewers visited participants at their home to record respiratory
      symptoms every 3 months in the child's first 2 years of life and every 6 months
      in the 3rd and 4th years. In the 4th year of follow-up, children were invited for
      standard lung function testing by spirometry quantified by forced vital capacity
      (FVC), forced expiratory volume in 1 sec (FEV(1)), and forced expiratory volume
      in 0.5 sec (FEV(0.5)) levels. Out of 258 children attending spirometry testing
      139 performed at least two acceptable exhalation efforts. Cohort children with
      acceptable spirometric measurements did not differ with respect to wheezing
      experience and exposure characteristics from those without. The study shows that
      episodic wheeze was reported in 28.1% of 4-year olds, 6.5% had transient wheeze,
      and 4.3% had recurrent wheeze. There was an increased frequency of wheezing
      symptoms and their duration in transient and recurrent wheezers. Adjusted
      multivariable regression models for gender and height showed that children who
      reported more than two episodes of wheezing at any point over the follow-up had
      FVC values lower by 120.5 ml (P = 0.016) and FEV(1) values lower by 98.3 ml (P =
      0.034) compared to those who did not report any wheezing; children experiencing
      more than 10 wheezing days by age 4 showed FVC deficit of 87.4 ml (P = 0.034) and
      FEV(1) values of 65.7 ml (P = 0.066). The ratios of FEV(1)/FVC%, and
      FEV(0.5)/FVC% were neither associated with wheezing episodes nor wheezing days.
      In recurrent wheezers, lung function decrement amounted to 207 ml of FVC, 175 ml
      of FEV(1), and 104 ml of FEV(0.5). In conclusion, our findings show that wheezing
      experience during early postnatal life may be associated with lung function
      deficit of restrictive character in preschool children and detailed history of
      wheeze in early postnatal life, even though not physician-confirmed, may help
      define the high risk group of children for poor lung function testing.

PMID- 20672364
TI  - Rectal washout and local recurrence of cancer after anterior resection.
AB  - BACKGROUND: Adenocarcinomas of the rectum shed viable cells, which have the
      ability to implant. Intraoperative rectal washout decreases the amount and
      viability of these cells, but there is no conclusive evidence of the effect of
      rectal washout on local recurrence after rectal cancer surgery. METHODS: Data
      were analysed from a population-based registry of patients who had anterior
      resection from 1995 to 2002 and were followed for 5 years. Rectal washout was
      performed at the discretion of the surgeon. National inclusion of patients with
      rectal cancer and follow-up was near complete (approximately 97 and 98 per cent
      respectively). RESULTS: A total of 4677 patients were analysed (3749 who had
      washout, 851 no washout and 77 with information missing); 52.0 per cent of
      patients in the washout group and 41.4 per cent in the no-washout group had
      preoperative radiotherapy (P < 0.001). Local recurrence rates were 6.0 and 10.2
      per cent respectively (P < 0.001). Univariable and multivariable logistic
      regression analyses produced odds ratios that favoured washout: 0.56 (95 per cent
      confidence interval (c.i.) 0.43 to 0.72) and 0.61 (0.46 to 0.80) respectively
      (both P < 0.001). In multivariable analysis restricted to patients who had
      curative surgery, the odds ratio was 0.59 (95 per cent c.i. 0.44 to 0.78; P <
      0.001). CONCLUSION: There was a more favourable outcome in patients after rectal
      washout than without.

PMID- 20672362
TI  - Conformational dynamics of actin: effectors and implications for biological
      function.
AB  - Actin is a protein abundant in many cell types. Decades of investigations have
      provided evidence that it has many functions in living cells. The diverse
      morphology and dynamics of actin structures adapted to versatile cellular
      functions is established by a large repertoire of actin-binding proteins. The
      proper interactions with these proteins assume effective molecular adaptations
      from actin, in which its conformational transitions play essential role. This
      review attempts to summarise our current knowledge regarding the coupling between
      the conformational states of actin and its biological function.

PMID- 20672365
TI  - The skin of Osedax (Siboglinidae, Annelida): an ultrastructural investigation of
      its epidermis.
AB  - The symbiotic polychaetes of the genus Osedax living on the bones of whale
      carcasses have become known as bone-eating worms. It is believed that whale bones
      are the source of nutrition for those gutless worms and that fatty acids are
      produced by their symbionts and transferred to the host. However, the symbionts
      are of the heterotrophic group Oceanospirillales and as such are not able to
      synthesize organic carbon de novo. Also, they are not housed in close contact to
      the bone material. We studied the ultrastructure of the integument overlying the
      symbiont housing trophosome in the ovisac region and the roots region and of the
      symbiont-free trunk region of Osedax to investigate the host's possible
      contribution in feeding for the whole symbiosis. The epidermis differs
      conspicuously between the three regions investigated and clearly points to being
      correlated with different functions carried out by those regions. The
      ultrastructure of the integument of the root region changed towards the ovisac
      region and corresponds with the change of the ultrastructure observed in the
      Osedax trophosome. We suggest that the epidermis in the root region is tightly
      linked to bone degradation and nutrient uptake. The trunk region possess two
      types of unicellular gland cells, at least one of which seems to be involved in
      secretion of the gelatinous tube of adult Osedax females.

PMID- 20672366
TI  - HOX gene expression in phenotypic and genotypic subgroups and low HOXA gene
      expression as an adverse prognostic factor in pediatric ALL.
AB  - BACKGROUND: HOX genes play an important role in both normal lymphopoiesis and
      leukemogenesis. However, HOX expression patterns in leukemia cells compared to
      normal lymphoid progenitors have not been systematically studied in acute
      lymphoblastic leukemia (ALL) subtypes. PROCEDURE: The RNA expression levels of
      HOXA, HOXB, and CDX1/2 genes were analyzed by qRT-PCR in a cohort of 61
      diagnostic pediatric ALL samples and FACS-sorted subpopulations of normal
      lymphoid progenitors. RESULTS: The RNA expression of HOXA7-10, HOXA13, and HOXB2
      4 genes was exclusively detected in leukemic cells and immature progenitors. The
      RNA expression of HOXB6 and CDX2 genes was exclusively detected in leukemic cells
      but not in B-lineage cells at any of the studied developmental stages. HOXA3-4,
      HOXA7, and HOXB3-4 genes were differentially expressed between BCP-ALL and T-ALL
      subgroups, and among genotypically defined MLL/AF4, TEL/AML1, BCR/ABL,
      hyperdiploid and normal karyotype subgroups. However, this differential
      expression did not define specific clusters in hierarchical cluster analysis.
      HOXA7 gene was low expressed at the RNA level in patients with hyperdiploid
      leukemia, whereas HOXB7 and CDX2 genes were low expressed in TEL/AML1-positive
      and BCR/ABL-positive cases, respectively. In contrast to previous findings in
      acute myeloid leukemia, high HOXA RNA expression was associated with an excellent
      prognosis in Cox's regression model (P = 0.03). In MLL/AF4-positive ALL, lower
      HOXA RNA expression correlated with the methylation status of their promoters.
      CONCLUSIONS: HOX gene RNA expression cannot discriminate leukemia subgroups or
      relative maturity of leukemic cells. However, HOXA RNA expression correlates with
      prognosis, and particular HOX genes are expressed in specific genotypically
      characterized subgroups.

PMID- 20672367
TI  - Ghosal hematodiaphyseal dysplasia: a rare cause of a myelophthisic anemia.
AB  - Ghosal hematodiaphyseal dysplasia syndrome (GHDD) is a rare clinical syndrome
      characterized by increased bone density and a severe, myelophthisic anemia. Few
      cases have been reported worldwide and there are no detailed descriptions of the
      associated hematologic abnormalities and long-term clinical outcomes after
      treatment. Here, we report two siblings with GHDD who were successfully treated
      with chronic, low dose, corticosteroid therapy. Although GHDD is uncommon, these
      cases illustrate the need to consider GHDD in patients with anemia and bone
      dysplasia and the use of chronic, low-dose steroid therapy.

PMID- 20672368
TI  - Effect of adapted physical activity sessions in the hospital on health-related
      quality of life for children with cancer: a cross-over randomized trial.
AB  - BACKGROUND: To assess the efficacy of adapted physical activity (APA) on health
      related quality of life (HRQoL) of hospitalized children and adolescents with
      cancer between 9 and 18 years of age. PROCEDURE: A two-sequence, four-period
      cross-over study, Activites Physiques en Oncologie Pediatrique (APOP), compared
      hospital stay with APA sessions versus hospital stay without APA sessions on
      children's HRQoL. Children and parents completed the child and parent forms,
      respectively, of a HRQoL questionnaire, the Child Health Questionnaire, on the
      last day of hospitalization. We used mixed linear regression to determine the
      effect of treatment, of treatment order and whether response to previous
      treatment influenced HRQoL. RESULTS: Thirty children were included (mean age 13.6
      +/- 2.9 years; 18 males). Cross-over analysis revealed no effect of period or
      interaction between APA and period. HRQoL was higher when children practiced than
      did not practice APA during their hospitalization, as reported by both children
      and parents, for the dimensions physical functioning (P < 0.0001), role/social
      physical (P = 0.001), self-esteem (P < 0.0001), and mental health (P < 0.0001).
      In addition, APA had a significant effect on the behavior dimension (P = 0.01),
      as reported by children, and on the bodily pain dimension (P = 0.0004), as
      reported by parents. The highest significant difference in scores between with
      and without APA was observed for the self-esteem dimension (P < 0.0001) for both
      children and parents. CONCLUSION: APA during hospitalization for children with
      cancer was associated with better HRQoL for most of the HRQoL psychological and
      physical dimensions. Whether this effect is specific for children with cancer
      should be explored.

PMID- 20672369
TI  - A cost-effectiveness analysis of coagulation testing prior to tonsillectomy and
      adenoidectomy in children.
AB  - BACKGROUND: The American Society of Pediatric Otolaryngology recommends pre
      operative coagulation testing only when indicated by history or physical exam.
      Nevertheless, many surgeons test all children scheduled for tonsillectomy and/or
      adenoidectomy (T&A). Studies of pre-operative screening have had conflicting
      results. A decision analysis model was constructed to address the costs and
      health outcome states of pre-operative screening strategies in children.
      PROCEDURE: A 14-day Markov model evaluated three strategies: (1) test all
      children for coagulation disorders; (2) test only those children with a pertinent
      history; and (3) perform no pre-operative testing. A literature search and a
      review of national databases estimated probabilities, costs, and utility data.
      Parameters then were varied widely in sensitivity analyses. Using a societal
      perspective and a cycle length of 1 day, we compared the strategies based on
      total costs and quality-adjusted life years (QALYs). RESULTS: Total costs for the
      strategies were $3,200 for testing all children, $3,083 for testing only those
      with a history finding, and $3,077 for not testing. Total utilities were 0.02579,
      0.02654, and 0.02659 QALYs, respectively. Cost-effectiveness ratios were most
      sensitive to variation in the cost of post-operative care and the probability of
      post-operative bleeding. The strategy of not testing was dominant in all
      sensitivity analyses. CONCLUSIONS: Our results demonstrate that not performing
      preoperative testing is the most cost-effective strategy. This was persistent in
      sensitivity analyses, indicating that the model was robust. These data may be
      helpful to institutions and organizations to formulate policies regarding pre
      operative coagulation for children without previous diagnoses of bleeding
      disorders.

PMID- 20672370
TI  - Initial testing (stage 1) of the multi-targeted kinase inhibitor sorafenib by the
      pediatric preclinical testing program.
AB  - BACKGROUND: Sorafenib is an inhibitor of multiple kinases (e.g., VEGF receptors,
      PDGFR, FLT3, RET, BRAF, KIT) and is approved by FDA for treatment of two adult
      cancers. The activity of sorafenib was evaluated against the PPTP's in vitro and
      in vivo panels. PROCEDURES: Sorafenib was evaluated against the PPTP in vitro
      panel using 96-hr exposure at concentrations ranging from 1.0 nM to 10.0 uM. It
      was tested against the PPTP in vivo panels at a dose of 60 mg/kg administered by
      oral gavage daily for 5 days per week, repeated for 6 weeks. RESULTS: In vitro
      sorafenib demonstrated cytotoxic activity, with a median IC(50) value of 4.3 uM.
      Twenty of 23 cell lines had IC(50) values between 1.0 and 10.0 uM. A single cell
      line (Kasumi-1) with an activating KIT mutation had an IC(50) value < 1.0 uM
      (IC(50) = 0.02 uM). In vivo sorafenib induced significant differences in event
      free survival (EFS) distribution compared to control in 27 of 36 (75%) of the
      evaluable solid tumor xenografts and in 1 of 8 (12.5%) of the evaluable ALL
      xenografts. Sorafenib induced tumor growth inhibition meeting criteria for
      intermediate activity (EFS T/C) in 15 of 34 (44%) evaluable solid tumor
      xenografts. No xenografts achieved an objective response. CONCLUSIONS: The
      primary in vitro activity of sorafenib was noted at concentrations above 1 uM,
      with the exception of a more sensitive cell line with an activating KIT mutation.
      The primary in vivo effect for sorafenib was tumor growth inhibition, which was
      observed across multiple histotypes.

PMID- 20672372
TI  - Predicting and facilitating survival of pediatric cancer patients: the ALC story.

PMID- 20672371
TI  - Influence of glutathione S-transferase A1, P1, M1, T1 polymorphisms on oral
      busulfan pharmacokinetics in children with congenital hemoglobinopathies
      undergoing hematopoietic stem cell transplantation.
AB  - BACKGROUND: Busulfan (BU), often used in high dose for myeloablation before
      hematopoietic stem cell transplantation (HSCT), has been implicated in certain
      HSCT toxicities, including the occurrence of hepatic veno-occlusive disease
      (HVOD). In addition to weight and age, gene polymorphisms in specific members of
      the glutathione-transferase (GST) gene family (A1, P1, M1, and T1), involved in
      BU metabolism, may play a role in the wide inter-patient variability in systemic
      BU concentrations. PROCEDURE: The present study integrated clinical data
      regarding the occurrence of HVOD, graft versus host disease (GVHD), BU
      pharmacokinetics and GSTA1, GSTP1, GSTM1, and GSTT1 genotypes of 18 children who
      received BU in their pre-HSCT conditioning regimen. The children were all treated
      for congenital hemoglobinopathies and were all of Arab Moslem descent. RESULTS:
      The data demonstrate an association between GSTA1 and GSTP1 genotypes and BU
      maximal concentration (C(max)) (P = 0.01, P = 0.02, respectively), area under the
      concentration-time curve (AUC) (P = 0.02, P = 0.01, respectively) and oral BU
      clearance/kg body weight (P < 0.02, P = 0.08, respectively). GSTM1-null
      individuals demonstrated lower BU-AUC/Kg compared to GSTM1-positive individuals.
      In addition, an association between GVHD and GSTM1-null genotype was found.
      CONCLUSIONS: GSTA1, GSTP1, and GSTM1 genotyping prior to HSCT in children with
      congenital hemoglobinopathies may allow better prediction of oral BU kinetics and
      the need for BU dose adjustment, as well as prediction of transplant related
      toxicity such as GVHD, thereby improving clinical outcome.

PMID- 20672373
TI  - ABCA12 mutations and autosomal recessive congenital ichthyosis: a review of
      genotype/phenotype correlations and of pathogenetic concepts.
AB  - Mutations in ABCA12 have been described in autosomal recessive congenital
      ichthyoses (ARCI) including harlequin ichthyosis (HI), congenital ichthyosiform
      erythroderma (CIE), and lamellar ichthyosis (LI). HI shows the most severe
      phenotype. CIE and LI are clinically characterized by fine, whitish scales on a
      background of erythematous skin, and large, thick, dark scales over the entire
      body without serious background erythroderma, respectively. To date, a total of
      56 ABCA12 mutations have been reported in 66 ARCI families including 48 HI, 10
      LI, and 8 CIE families of African, European, Pakistani/Indian, and Japanese
      origin (online database: http://www.derm-hokudai.jp/ABCA12/). A total of 62.5% of
      reported ABCA12 mutations are expected to lead to truncated proteins. Most
      mutations in HI are truncation mutations and homozygous or compound heterozygous
      truncation mutations always results in HI phenotype. In CIE families, at least
      one mutation on each allele is typically a missense mutation. Combinations of
      missense mutations in the first ATP-binding cassette of ABCA12 underlie the LI
      phenotype. ABCA12 is a keratinocyte lipid transporter associated with lipid
      transport in lamellar granules, and loss of ABCA12 function leads to a defective
      lipid barrier in the stratum corneum, resulting in an ichthyotic phenotype.
      Recent work using mouse models confirmed ABCA12 roles in skin barrier formation.

PMID- 20672374
TI  - Experience with carrier screening and prenatal diagnosis for 16 Ashkenazi Jewish
      genetic diseases.
AB  - The success of prenatal carrier screening as a disease prevention strategy in the
      Ashkenazi Jewish (AJ) population has driven the expansion of screening panels as
      disease-causing founder mutations have been identified. However, the carrier
      frequencies of many of these mutations have not been reported in large AJ
      cohorts. We determined the carrier frequencies of over 100 mutations for 16
      recessive disorders in the New York metropolitan area AJ population. Among the
      100% AJ-descended individuals, screening for 16 disorders resulted in ~1 in 3.3
      being a carrier for one disease and ~1 in 24 for two diseases. The carrier
      frequencies ranged from 0.066 (1 in 15.2; Gaucher disease) to 0.006 (1 in 168;
      nemaline myopathy), which averaged ~15% higher than those for all screenees.
      Importantly, over 95% of screenees chose to be screened for all possible AJ
      diseases, including disorders with lower carrier frequencies and/or
      detectability. Carrier screening also identified rare individuals homozygous for
      disease-causing mutations who had previously unrecognized clinical
      manifestations. Additionally, prenatal testing results and experience for all 16
      disorders (n = 574) are reported. Together, these data indicate the general
      acceptance, carrier frequencies, and prenatal testing results for an expanded
      panel of 16 diseases in the AJ population.

PMID- 20672376
TI  - pfSNP: An integrated potentially functional SNP resource that facilitates
      hypotheses generation through knowledge syntheses.
AB  - Currently, >14,000,000 single nucleotide polymorphisms (SNPs) are reported.
      Identifying phenotype-affecting SNPs among these many SNPs pose significant
      challenges. Although several Web resources are available that can inform about
      the functionality of SNPs, these resources are mainly annotation databases and
      are not very comprehensive. In this article, we present a comprehensive, well
      annotated, integrated pfSNP (potentially functional SNPs) Web resource
      (http://pfs.nus.edu.sg/), which is aimed to facilitate better hypothesis
      generation through knowledge syntheses mediated by better data integration and a
      user-friendly Web interface. pfSNP integrates >40 different algorithms/resources
      to interrogate >14,000,000 SNPs from the dbSNP database for SNPs of potential
      functional significance based on previous published reports, inferred potential
      functionality from genetic approaches as well as predicted potential
      functionality from sequence motifs. Its query interface has the user-friendly
      "auto-complete, prompt-as-you-type" feature and is highly customizable,
      facilitating different combination of queries using Boolean-logic. Additionally,
      to facilitate better understanding of the results and aid in hypotheses
      generation, gene/pathway-level information with text clouds highlighting enriched
      tissues/pathways as well as detailed-related information are also provided on the
      results page. Hence, the pfSNP resource will be of great interest to scientists
      focusing on association studies as well as those interested to experimentally
      address the functionality of SNPs.

PMID- 20672375
TI  - Molecular analysis expands the spectrum of phenotypes associated with GLI3
      mutations.
AB  - A range of phenotypes including Greig cephalopolysyndactyly and Pallister-Hall
      syndromes (GCPS, PHS) are caused by pathogenic mutation of the GLI3 gene. To
      characterize the clinical variability of GLI3 mutations, we present a subset of a
      cohort of 174 probands referred for GLI3 analysis. Eighty-one probands with
      typical GCPS or PHS were previously reported, and we report the remaining 93
      probands here. This includes 19 probands (12 mutations) who fulfilled clinical
      criteria for GCPS or PHS, 48 probands (16 mutations) with features of GCPS or PHS
      but who did not meet the clinical criteria (sub-GCPS and sub-PHS), 21 probands (6
      mutations) with features of PHS or GCPS and oral-facial-digital syndrome, and 5
      probands (1 mutation) with nonsyndromic polydactyly. These data support
      previously identified genotype-phenotype correlations and demonstrate a more
      variable degree of severity than previously recognized. The finding of GLI3
      mutations in patients with features of oral-facial-digital syndrome supports the
      observation that GLI3 interacts with cilia. We conclude that the phenotypic
      spectrum of GLI3 mutations is broader than that encompassed by the clinical
      diagnostic criteria, but the genotype-phenotype correlation persists. Individuals
      with features of either GCPS or PHS should be screened for mutations in GLI3 even
      if they do not fulfill clinical criteria.

PMID- 20672377
TI  - Comparison analysis of primary ligand-binding sites in seven-helix membrane
      proteins.
AB  - Seven-helix transmembrane proteins, including the G-protein-coupled receptors
      (GPCRs), mediate a broad range of fundamental cellular activities through binding
      to a wide range of ligands. Understanding the structural basis for the ligand
      binding selectivity of these proteins is of significance to their structure-based
      drug design. Comparison analysis of proteins' ligand-binding sites provides a
      useful way to study their structure-activity relationships. Various computational
      methods have been developed for the binding-site comparison of soluble proteins.
      In this work, we applied this approach to the analysis of the primary ligand
      binding sites of 92 seven-helix transmembrane proteins. Results of the studies
      confirmed that the binding site of bacterial rhodopsins is indeed different from
      all GPCRs. In the latter group, further comparison of the binding sites indicated
      a group of residues that could be responsible for ligand-binding selectivity and
      important for structure-based drug design. Furthermore, unexpected binding-site
      dissimilarities were observed among adrenergic and adenosine receptors,
      suggesting that the percentage of the overall sequence identity between a target
      protein and a template protein alone is not sufficient for selecting the best
      template for homology modeling of seven-helix membrane proteins. These results
      provided novel insight into the structural basis of ligand-binding selectivity of
      seven-helix membrane proteins and are of practical use to the computational
      modeling of these proteins.

PMID- 20672378
TI  - Keratosis Follicularis Spinulosa Decalvans is caused by mutations in MBTPS2.
AB  - Keratosis Follicularis Spinulosa Decalvans (KFSD) is a rare genetic disorder
      characterized by development of hyperkeratotic follicular papules on the scalp
      followed by progressive alopecia of the scalp, eyelashes, and eyebrows.
      Associated eye findings include photophobia in childhood and corneal dystrophy.
      Due to the genetic and clinical heterogeneity of similar disorders, a definitive
      diagnosis of KFSD is often challenging. Toward identification of the causative
      gene we reanalyzed a large Dutch KFSD family. SNP arrays (1 M) redefined the
      locus to a 2.9-Mb region at Xp22.12-Xp22.11. Screening of all 14 genes in the
      candidate region identified MBTPS2 as the candidate gene carrying a c.1523A>G
      (p.Asn508Ser) missense mutation. The variant was also identified in two unrelated
      X-linked KFSD families and cosegregated with KFSD in all families. In symptomatic
      female carriers, skewed X-inactivation of the normal allele matched with
      increased severity of symptoms. MBTPS2 is required for cleavage of sterol
      regulatory element-binding proteins (SREBPs). In vitro functional expression
      studies of the c.1523A>G mutation showed that sterol responsiveness was reduced
      by half. Other missense mutations in MBTPS2 have recently been identified in
      patients with IFAP syndrome. We postulate that both phenotypes are in the
      spectrum of one genetic disorder with a partially overlapping phenotype.

PMID- 20672379
TI  - Locus-specific database domain and data content analysis: evolution and content
      maturation toward clinical use.
AB  - Genetic variation databases have become indispensable in many areas of health
      care. In addition, more and more experts are depositing published and unpublished
      disease-causing variants of particular genes into locus-specific databases
      (LSDBs). Some of these databases contain such extensive information that they
      have become known as knowledge bases. Here, we analyzed 1,188 LSDBs and their
      content for the presence or absence of 44 content criteria related to database
      features (general presentation, locus-specific information, database structure)
      and data content (data collection, summary table of variants, database querying).
      Our analyses revealed that several elements have helped to advance the field and
      reduce data heterogeneity, such as the development of specialized database
      management systems and the creation of data querying tools. We also identified a
      number of deficiencies, namely, the lack of detailed disease and phenotypic
      descriptions for each genetic variant and links to relevant patient
      organizations, which, if addressed, would allow LSDBs to better serve the
      clinical genetics community. We propose a structure, based on LSDBs and closely
      related repositories (namely, clinical genetics databases), which would
      contribute to a federated genetic variation browser and also allow the
      maintenance of variation data.

PMID- 20672380
TI  - Liver enzymes and cardiovascular outcomes: a new research agenda.

PMID- 20672381
TI  - Suggestion of a dual-functional agent for future trials in nonalcoholic fatty
      liver disease.

PMID- 20672382
TI  - Complications of alcoholic liver cirrhosis: active assessment by endoscopy and
      sonography.

PMID- 20672383
TI  - Vitamin D controls T cell activation: implication for causal association between
      vitamin D deficiency and fibrosis in chronic hepatitis C.

PMID- 20672384
TI  - Therapeutic interventions for fructose-induced fatty liver disease are premature.

PMID- 20672385
TI  - Lynch syndrome-associated mutations in MSH2 alter DNA repair and checkpoint
      response functions in vivo.
AB  - The DNA mismatch repair (MMR) pathway is essential in maintaining genomic
      stability through its role in DNA repair and the checkpoint response. Loss of DNA
      MMR underlies the hereditary cancer disease Lynch Syndrome (LS). Germline
      mutations in MSH2 account for approximately 40% of LS patients and of these, 18%
      are missense variants. One important clinical challenge has been discriminating
      between missense variants that are pathogenic and those that are not. Current
      analysis of missense mutations in MSH2 is performed using a combination of
      clinical, biochemical, and functional data; however, suitable cell culture models
      to test the various functions of the DNA MMR proteins are lacking. Here, we have
      generated human cell lines stably expressing a subset of MSH2 missense mutants
      and tested their effect on DNA repair and checkpoint response functions. We have
      expanded on previous biochemical and functional analyses performed in non-human
      systems to further understand defects conferred by this subset of single amino
      acid alterations. The functional characterization of MSH2 missense mutants
      combined with clinical and biochemical data is essential for appropriate patient
      management and genetic counseling decisions.

PMID- 20672386
TI  - Health-related quality of life and sorafenib.

PMID- 20672387
TI  - Hepatic steatosis with hepatitis B virus/hepatitis C virus dual infection.

PMID- 20672388
TI  - Atomic force microscopy of biological samples.
AB  - The ability to evaluate structural-functional relationships in real time has
      allowed scanning probe microscopy (SPM) to assume a prominent role in post
      genomic biological research. In this mini-review, we highlight the development of
      imaging and ancillary techniques that have allowed SPM to permeate many key areas
      of contemporary research. We begin by examining the invention of the scanning
      tunneling microscope (STM) by Binnig and Rohrer in 1982 and discuss how it served
      to team biologists with physicists to integrate high-resolution microscopy into
      biological science. We point to the problems of imaging nonconductive biological
      samples with the STM and relate how this led to the evolution of the atomic force
      microscope (AFM) developed by Binnig, Quate, and Gerber, in 1986.
      Commercialization in the late 1980s established SPM as a powerful research tool
      in the biological research community. Contact mode AFM imaging was soon
      complemented by the development of non-contact imaging modes. These non-contact
      modes eventually became the primary focus for further new applications including
      the development of fast scanning methods. The extreme sensitivity of the AFM
      cantilever was recognized and has been developed into applications for measuring
      forces required for indenting biological surfaces and breaking bonds between
      biomolecules. Further functional augmentation to the cantilever tip allowed
      development of new and emerging techniques including scanning ion-conductance
      microscopy (SICM), scanning electrochemical microscope (SECM), Kelvin force
      microscopy (KFM) and scanning near field ultrasonic holography (SNFUH).

PMID- 20672389
TI  - Quantification of human body fat tissue percentage by MRI.
AB  - The MRI-based evaluation of the quantity and regional distribution of adipose
      tissue is one objective measure in the investigation of obesity. The aim of this
      article was to report a comprehensive and automatic analytical method for the
      determination of the volumes of subcutaneous fat tissue (SFT) and visceral fat
      tissue (VFT) in either the whole human body or selected slices or regions of
      interest. Using an MRI protocol in an examination position that was convenient
      for volunteers and patients with severe diseases, 22 healthy subjects were
      examined. The software platform was able to merge MRI scans of several body
      regions acquired in separate acquisitions. Through a cascade of image processing
      steps, SFT and VFT volumes were calculated. Whole-body SFT and VFT distributions,
      as well as fat distributions of defined body slices, were analysed in detail.
      Complete three-dimensional datasets were analysed in a reproducible manner with
      as few operator-dependent interventions as possible. In order to determine the
      SFT volume, the ARTIS (Adapted Rendering for Tissue Intensity Segmentation)
      algorithm was introduced. The advantage of the ARTIS algorithm was the
      delineation of SFT volumes in regions in which standard region grow techniques
      fail. Using the ARTIS algorithm, an automatic SFT volume detection was feasible.
      MRI data analysis was able to determine SFT and VFT volume percentages using new
      analytical strategies. With the techniques described, it was possible to detect
      changes in SFT and VFT percentages of the whole body and selected regions. The
      techniques presented in this study are likely to be of use in obesity-related
      investigations, as well as in the examination of longitudinal changes in weight
      during various medical conditions.

PMID- 20672390
TI  - Ethical dilemmas in treating clients with eating disorders: A review and
      application of an integrative ethical decision-making model.
AB  - Ethical dilemmas frequently arise in the treatment of clients with eating
      disorders, and clinicians regularly encounter an array of ethical challenges
      related to whether or not overt and covert coercive tactics should be
      implemented. In this paper, the authors provide an overview of perplexing ethical
      questions relevant to medical, nutritional and psychological treatment of clients
      with eating disorders including imposed treatment, enforced feeding, the duty to
      protect minors and adults, the determination of competence and capacity among
      medically comprised clients, and the effectiveness of coercive treatment for
      clients with eating disorders. The processes of ethical decision-making in terms
      of ethical principles, professional codes of conduct, the existing empirical
      literature and the use of a decision-making framework are explored. Taking a
      collaborative and client-sensitive approach, the authors outline and apply an
      integrative ethical decision-making model to facilitate clinicians' decision
      making process.

PMID- 20672391
TI  - A new diagnostic provocation test for carpal tunnel syndrome: Okutsu test.
AB  - Many authors have reported various clinical provocation tests for diagnosis of
      carpal tunnel syndrome, however, some tests cannot be administered correctly on
      patients who suffer from restricted wrist joint movement. We compiled positive
      rates from a new diagnostic provocation test (Okutsu test) carried out on 3474
      hands, and compared them and their success rates with results from other
      provocation tests performed on these same hands. The Okutsu test positive rate
      was 72.4%. There were statistical differences between Phalen test (69.8%) and
      wrist-extension test (60.2%) results. The Okutsu test success rate was 99.9% and
      there were statistical differences between Phalen test (52.8%) and wrist
      extension test (56.8%) results. There were no statistical differences between
      percussion test at the wrist results in positive rate (71.1%) and in success rate
      (99.7%). The Okutsu test positive rate is high and it serves as a reliable
      screening test for clinical diagnosis of carpal tunnel syndrome.

PMID- 20672392
TI  - Katz and Stirrat hand diagram revisited.
AB  - Katz and Stirrat devised a hand diagram, which uses subjective information from
      the patient for the diagnosis of carpal tunnel syndrome (CTS). They reported a
      good result. We tested the inter-observer and intra-observer reliability of this
      hand diagram. Twenty five consecutive patients with a diagnosis of CTS, 25 with
      other common hand and wrist problems but CTS and 25 healthy individuals were
      prospectively recruited. Each patient filled in a hand diagram. Two experienced
      hand surgeon scored the diagrams blindly on two different sittings four-week
      apart. The intra-class correlation coefficient (ICC) and Cohen's Kappa were used
      for intra and inter-observer reliability respectively. The intra-observer
      agreement was poor (ICC 95% 0.33-0.65) and inter-observer was fair (Kappa =
      0.241). This study does not support the use of Katz and Stirrat Hand Diagram for
      the diagnosis of carpal tunnel syndrome in place if a thorough clinical
      examination.

PMID- 20672393
TI  - A comparison of workers' compensation patients and nonworkers' compensation
      patients undergoing endoscopic carpal tunnel release.
AB  - This study compares results of endoscopic carpal tunnel release using the two
      portal technique in two groups of patients based on whether or not they were
      receiving workers' compensation. There were 50 patients in the worker's
      compensation group and 63 in the nonworker's compensation group. Mean follow-up
      was 40.8 months and 44.8 months, respectively. Duration of symptoms before
      surgery was statistically different in the two groups, 13.6 months in the
      worker's compensation groups compared to 26.2 months in the nonworker's
      compensation group. Worker's compensation patients tended to be younger, have
      shorter duration of symptoms before surgery, report lower postoperative activity
      levels, have more subsequent surgeries, and have mediocre results when compared
      to nonworker's compensation patients. There was no statistically significant
      difference in the rate or timing of return to work. Our series of 113 patients
      who had endoscopic carpal tunnel release indicates that careful patient selection
      is necessary to achieve satisfactory outcomes in worker's compensation patients.

PMID- 20672394
TI  - Risk factors for trigger finger occurrence after carpal tunnel release.
AB  - Carpal tunnel syndrome and trigger finger (TF) are common ailments managed by
      hand surgeons, but it is unclear whether these conditions are related. The
      purpose of this study was to determine whether there are risk factors for the new
      onset of TF after carpal tunnel release (CTR). A retrospective chart review was
      performed on 792 CTR surgeries and multiple variables were compared between
      patients who did and did not develop TF after CTR. The incidence of new-onset TF
      after CTR was 6.3%. Multivariate regression analysis showed that osteoarthritis
      and undergoing an endoscopic procedure were the only two independent risk
      factors. Based on these results, we recommend that for endoscopic CTR, the higher
      incidence of TF should be discussed preoperatively as a potential sequelae.
      Further, patients with osteoarthritis should be informed of their greater risk of
      developing TF postoperatively and should be monitored closely for expeditious
      detection and management of new-onset TF.

PMID- 20672395
TI  - Arthroscopic wafer resection for ulnar impaction syndrome: prediction of
      outcomes.
AB  - Twenty-six patients with mean age of 38.5 (range 18-59), from 1998 to 2005, with
      ulnar impaction syndrome who failed nonoperative treatments were included in our
      study. Patients' age, history of previous wrist fracture, presence of MRI signs
      and ulnar variance were recorded as variables. Also, patients' postoperative
      strength (compared to the contralateral wrist) and pain relief were collected as
      outcome measurements. Twenty-two patients (84.6%) had either good or excellent
      pain relief (median 4, range 1-4). Significant correlation was found between MRI
      findings and postop pain relief (r = 0.53, p < or = 0.01). History of previous
      distal radius fractures was negatively correlated with pain relief (r = -0.50, p
      < or = 0.01). No correlation was found between postop strength and any of the
      variables. Presence of MRI signs of UIS is a predictor of good outcome in
      arthroscopic wafer resection.

PMID- 20672396
TI  - Bone-cement interface strength in distal radii using two medullary canal
      preparation techniques: carbon dioxide jet cleaning versus syringed saline.
AB  - PURPOSE: Loosening is an important cause of failure of upper limb arthroplasty
      and improvement in cementation techniques may limit this. The currently accepted
      medullary canal preparation techniques use saline washing and gauze drying.
      Another method of bone preparation uses carbon dioxide compression gas jet which
      blows debris from the canal, whilst simultaneously drying the bone. We compared
      the push out strengths of cement plugs in sections of human cadaveric radii that
      had been prepared using either syringed saline or carbon dioxide jet cleaning.
      METHODS: Following bone preparation, four radii in each group, were cemented in a
      standardised fashion, and cut into 1 cm sections. An Instron materials testing
      machine was used to measure the force needed to push the cement plug out of the
      bone section. RESULTS: The force needed to push out the cement plug was
      significantly higher in the carbon dioxide jet (median 580.61, IQR 429.10-650.05)
      as compared to the saline group (median 366.57N, IQR 271.05-502.23), P = 0.009.
      The mechanism of failure of the bone-cement interface also differed between the
      two groups, with 100% of the sectioned cortices fracturing prior to cement
      extrusion in the carbon dioxide jet group, but only 23% of the sectioned cortices
      doing so in the saline group. CONCLUSION: Our results suggest that there is a
      statistically stronger macro-interlock at the bone-cement interface after
      preparation of the medullary canals of radii using a carbon dioxide compression
      gas jet as compared to saline irrigation.

PMID- 20672397
TI  - An analysis of partial width flexor tendon graft preparation on porcine models:
      the optimal split?
AB  - Partial width tendon grafts are commonly used in upper limb reconstructive
      surgery. Different techniques are described to harvest the graft including a
      "cheese wire" technique to split the tendon along its fibres with a filament.
      However no study has looked at the best material for this purpose. Fresh flexor
      tendons from pigs' trotters were used to analyse the splitting qualities of 11
      different suture materials. The qualities assessed were: whether the suture
      material was successful in splitting the tendon, the average force required to
      split the tendon and the resulting quality of the spilt tendon graft. Whilst wire
      sutures produced a high quality of graft, they were awkward to use as they
      necessitated handling with a holder due to the higher forces required to split
      the tendon. Fibrewire provided the best result with respect to graft quality and
      ease of method as it combined the cutting strength of wire with the handling
      characteristics of a braided suture.

PMID- 20672398
TI  - Current management of Jersey finger in rugby players: case series and literature
      review.
AB  - We discuss a combination of established and modern techniques in the
      investigation and management of traumatic flexor digitorum profundus rupture
      ('Rugger Jersey Finger') in seven cases (male rugby players ranging from 15 to 30
      years of age; mean = 26). We discuss the use of X-ray and ultrasound
      investigation followed by various surgical repairs including intraosseous
      sutures, suture anchors, tendon lengthening and "pull-through suture over button"
      repairs. Functional outcome at outpatient follow-up is discussed in each case.
      Type I, II and Vb injuries were identified. Patients presenting early attained
      good functional outcome. Six patients received surgery within ten days of injury
      and attained satisfactory outcome at follow-up. One patient presented late and
      required a tendon lengthening procedure to manage myostatic contracture.
      Ultrasound imaging proved valuable in diagnosis and pre-operative planning.
      Numerous surgical repairs were used and all associated with a positive outcome
      providing there is adequate patient compliance.

PMID- 20672399
TI  - Hand surgery on anticoagulated patients: a prospective study of 121 operations.
AB  - The management of anticoagulated patients requiring surgery presents a challenge
      to hand surgeons. The risk of bleeding related complications needs to be weighed
      up against the increased risk of thrombotic events if anticoagulants are altered
      or ceased. There is literature reporting the safety of hand, skin, eye and dental
      surgery on patients taking anticoagulants, and there is literature highlighting
      the risks associated with altering regular anticoagulant medication. However, it
      is common practice to cease or alter patients' anticoagulants peri-operatively
      for hand surgery. We report a prospective study of 107 patients taking
      anticoagulants who underwent 121 hand operations from December 2005 to August
      2009. There was only one significant complication, that being a haematoma which
      occurred in a patient taking clopidogrel. We conclude that interruption to
      therapy with warfarin (provided the INR is not greater than 3.0), clopidogrel or
      clopidogrel with aspirin is unnecessary for patients undergoing hand surgery.

PMID- 20672400
TI  - Myositis ossificans of the supinator muscle causing posterior interosseous nerve
      palsy: a case report.
AB  - Some tumors or tumorous conditions causing posterior interosseous nerve palsy are
      well documented, but myositis ossificans causing the palsy of this nerve has not
      been described. We present a case of posterior interosseous nerve palsy caused by
      myositis ossificans of the supinator muscle.

PMID- 20672401
TI  - Salvage of a failed Sauve-Kapandji procedure using a total distal radio-ulnar
      joint replacement.
AB  - This is the first report in the literature of a patient treated with a DRUJ
      replacement after Sauve-Kapandji procedure failed due to pain and instability.
      The DRUJ replacement is an unconstrained, biomechanically more advantageous
      implant which can confer stability in cases where soft tissues are inadequate. We
      describe the treatment and outcome of persistent ulnar instability with a distal
      radio-ulnar joint replacement following failed salvage procedures for a malunion
      of a distal radius fracture.

PMID- 20672402
TI  - Simultaneous fractures of the scaphoid, proximal and distal end of the radius: a
      case report.
AB  - We report a case of injury, simultaneous fractures of scaphoid, distal radius and
      radial head. It was treated by fixation operatively, and then early active range
      of motion exercise was started.

PMID- 20672403
TI  - Benign fibrous histocytoma of the distal radius: a report of a case and a review
      of the literature.
AB  - Benign fibrous histocytoma of bones is a very rare tumour and only a few cases
      have been reported. We report a case of 40-year-old patient with no significant
      previous medical history who presented with a painful lesion in his right wrist
      joint. Incision biopsy was done and there was a histological picture similar to a
      metaphyseal fibrous defect (non-ossifying fibroma). This was managed with
      excision of the lesion and filling the defect with cancellous and cortical bone
      grafts from the left iliac bone. To our knowledge, this is the second case report
      of a benign fibrous histocytoma involving the distal radius in adult. In this
      case report, we review similar cases in the literature and discuss the
      differential diagnoses of this lesion.

PMID- 20672404
TI  - Extensor tendon rupture due to cutaneous leichmaniasis: a case report.
AB  - Acute cutaneous leishmaniasis is a parasitic infectious disease prevalent in
      tropical areas. Most doctors in non-endemic countries are not familiar with this
      disease. Spontaneous tendon ruptures occurring by different mechanisms have been
      described in the literature but a tendon rupture caused by a skin ulcer secondary
      to a parasitic infection has not been reported before. In this article clinical
      and diagnostic features of cutaneous leishmaniasis are reviewed and a case with
      spontaneous extensor tendon rupture due to cutaneous leishmaniasis is presented.

PMID- 20672405
TI  - Triggering of extensor pollicis longus tendon: case report.
AB  - Triggering of extensor pollicis longus (EPL) tendon is an uncommon phenomenon
      with a few reports in the previous literature. Because of its rarity, the
      recommendations for management are sparse. We report a case of triggering EPL
      tendon secondary to the tendon nodule in a 42-year-old woman treated with the
      surgical decompression. The intraoperative findings, surgical technique and
      outcome of this case are described.

PMID- 20672406
TI  - Radiolunate fusion using vascularized radius bridging graft for the treatment of
      advanced Kienbock disease: two cases report.
AB  - We present here two cases wherein we performed radiolunate fusion using
      vascularized radius graft with the vascular pedicle of the fourth extensor
      compartment artery (fourth ECA) for the treatment of Bain's grade 2A Kienbock
      disease with incongruity of the radiolunate joint. The dorsodistal radius graft
      was levered out and mobilized on the pedicle of the fourth ECA; then the
      vascularized dorsodistal radius was shifted 1 cm distally and bridges were
      created between the radius and the lunate. The radiolunate joint was completely
      fused in both cases at three months after surgery. The capitolunate joint
      maintained congruity after surgery. The Mayo wrist score was 75 points, and the
      DASH (JSSH version) score for the two cases was 2.5 and 4.2 points, respectively.
      Radiolunate fusion using the vascularized radius bridging procedure is one of the
      satisfactory methods for treating advanced Kienbock disease, especially in Bain's
      grade 2A cases.

PMID- 20672407
TI  - Surgical treatment of mucous cysts on fingers without skin excision.
AB  - Mucous cysts on the fingers are commonly treated by excision followed by a
      rotation flap or skin graft. However, such procedures require skin donors or
      large incisions. Therefore, a less invasive procedure is needed. Here, we report
      a surgical treatment method that does not require the excision of the cyst. A
      skin flap was made around the cyst and raised; the pedicle of the cyst was then
      electrodesiccated or ligated, and the contents of the cyst were evacuated. If the
      pedicle could not be clearly identified, the backside of the flap was
      electrodesiccated to break the connection between the cyst and the distal
      interphalangeal joint. The skin flap was replaced and sutured. The flaps became
      almost normal during the follow-up period. No complications or recurrences
      occurred in any of the six cases that were treated. Our procedure appears to be
      an effective and less-invasive treatment for mucous cysts of the fingers.

PMID- 20672408
TI  - [Spatial patterns of genetic differentiation in Brachionus calyciflorus species
      complex].
AB  - To understand spatial patterns of genetic differentiation in the Brachionus
      calyciflorus species complex, the rDNA ITS regions of 124 rotifer clones
      collected from eight geographic regions in East China were sequenced and
      analyzed. A total of 73 haplotypes were defined, and were grouped into three
      clades by the phylogenetic trees. The divergences of ITS sequence among the three
      clades ranged from 4.2% to 25.3%, indicating the occurrence of three cryptic
      species (cryptic species I, cryptic species II and cryptic species III). The
      sympatric co-occurrence of these cryptic species was observed at Guangzhou,
      Danzhou and Wuhu. The nucleotide diversity in B. calyciflorus complex was higher,
      and so was haplotype diversity. Within cryptic species III, the higher genetic
      differentiation might be attributed to fragmentation and restricted gene flow. In
      addition, the rapid increase of colonizers after an ambiguous glacial bottleneck
      might interfere with effective gene flow and accelerate genetic differentiation
      of geographic populations. The nested clade analysis suggested to some extent the
      geographic structure, and the non-significant correlation existed between the
      geographic distance and the average pairwise difference between populations (Da)
      as well as Fst. The Younger Dryas(YD) Event after the last full glacial period
      might has considerable effect on the patterns of geographic structure and
      distribution of cryptic B. calyciflorus species. During the YD event, the three
      cryptic species probably retreated and co-occurred in multiple relict refugia to
      the south of Nanling area. Long-distance colonization possibly coupled with
      subsequent fragmentation might be the main reason of the current patterns of
      geographic structure. The geographic distribution of B. calyciflorus complex on a
      global scale might be attributed to the motion of continental plates.

PMID- 20672409
TI  - [Phylogenetic relationships among Cobitoidea based on mitochondrial ND4 and ND5
      gene sequences].
AB  - In the present study, we cloned and sequenced 10 new ND4 and ND5 gene sequences
      of Cobitoidea. These sequences were used to reconstruct phylogenetic
      relationships together with those of 15 other species downloaded from GenBank.
      The results showed that the length of ND4 gene sequence was 1 380-1 387 bp with
      ATG as starting codon and incomplete termination signal as terminated codon; the
      length of ND5 gene sequence was 1 821-1 839 bp with ATG as starting codon and TAA
      or TAG as terminated codon; three tRNA genes coding tRNAs that carry hisidine,
      serine and leucine respectively, were inserted between ND4 and ND5 genes. A, T, C
      and G accounted for 30.4%, 27.3%, 14.2% and 28.1% in ND4/ND5 gene (including
      intervening three tRNA genes). The content of A+T (57.7%) is higher than that of
      G+C (42.3%). The estimated Ti/Tv ratio was 1.586. With Danio rerio and Cyprinus
      carpio as outgroups, the phylogenetic relationships of Cobitoidea were analyzed
      using maximum parsimony (MP) method, maximum likelihood (ML) method and Bayesian
      analyses (BI). Results of all the three methods indicated that Cobitinae,
      Nemacheilinae, Botiinae, Balitoridae and Vaillantellidae were all monophyletic
      respectively, and their interrelationships were: (Vaillantellidae + (Botiinae +
      (Cobitinae + (Nemacheilinae + Balitoridae)))), which was consistent with the
      previous studies based on the whole mitogenome and some nuclear genes sequences
      (eg. RAG1 gene). However, the present results differ from those based upon other
      mtDNA genes sequences (e.g. the cyt b and D-loop showed that Nemacheilinae
      grouped with Cobitinae forming sister-group, then they clustered with
      Balitoridae). The difference could be due to the phylogenetic information carried
      by different length sequence: Longer sequences carry more information and result
      in more reliable phylogenetic trees.

PMID- 20672410
TI  - [Geographical speciation process of the genus Lepturichthys (Cypriniformes:
      Balitoridae)].
AB  - The genus Lepturichthys is endemic in China, including two valid species, L.
      fimbriata and L. dolichopterus. The former is widely distributed in the Upper and
      Middle Yangtze River, while the latter only in Minjiang River. In the present
      study, the mitochondrial cytochrome b gene sequences were analyzed for 20
      individuals of L. fimbriata collected from the Upper and Middle Yangtze River and
      eight individuals of L. dolichopterus collected from Minjiang River. This paper
      aimed to investigate the geographical speciation process of the genus
      Lepturichthys. The results showed that the genetic variations among different
      haplotypes of L. fimbriata ranged from 0.1% to 1.8%, with an average of 0.7%, and
      from 0.6% to 1.3%, with an average of 0.7% among different haplotypes of L.
      dolichopterus. The variations between L. fimbriata and L. dolichopterus were also
      very low, ranging from 0.2% to 1.8%, with an average of 0.9%. Two methods,
      Neighbor Joining (NJ) and Bayesian analysis (BI), were used for constructing the
      molecular phylogenetic trees. Both NJ and BI trees indicated that all
      Lepturichthys specimens formed as a monophyletic group; the L. dolichopterus
      samples also formed as monophyletic group, having a derived position in the
      phylogenetic trees, while the L. fimbriata samples formed as a paraphyletic
      group. Both L. fimbriata and L. dolichopterus are valid species in morphology.
      Based on molecular and morphological data, we presumed that the geographical
      speciation process of the genus Lepturichthys could be as following: during the
      Quaternary Glacial period, L. fimbriata in the Middle and Lower Yangtze River
      dispersed to the drainages of Southeast China along the Continental Shelf of East
      China Sea, one population spread to the Minjiang River and envolved as a new
      species (L. dolichopterus) because of considerable environmental difference,
      while the remaining L. fimbriata populations in the Yangtze River formed as a
      paraphyly. The other similar geographical speciation patterns are discussed in
      the present study as well.

PMID- 20672411
TI  - [Molecular characterization and evolutional analysis of liportein lipase and
      hepatic lipase gene in Chinese Sturgeon and other six freshwater fishes].
AB  - In order to study the structural, functional and molecular evolutional
      relationship of fish liportein lipase (LPL) and hepatic lipase (HL) genes, seven
      liver LPL and HL cDNA partial sequences were isolated from Acipenser sinensis,
      Hypophthalmichthys molitrix, Aristichthys nobilis, Ctenopharyngodon idellus,
      Cirrhinus molitorella, Oreochromis niloticus, Channa maculate by RT-PCR. Three
      full-length cDNA sequences of LPL, HL of Acipenser sinensis and LPL of
      Hypophthalmichthys molitrix were obtained by RACEs. From the sequence analysis
      and homologous results, the amino acid sequences of LPL and HL are relatively
      conserved in mammals, birds and fishes. Taken together with these obtained amino
      acid sequences and sequences of all known LPL, HL, EL and PL from other
      vertebrates, a phylogenetic tree was constructed by neighbor-joining method. The
      result supports that all of them belong to lipase family.

PMID- 20672413
TI  - [cDNA cloning, characterization and mRNA expression of a profilin from the
      swimming crab Portunus trituberculatus].
AB  - We isolated and characterized the profilin full-length cDNA from hemocytes of
      swimming crab Portunus trituberculatus. The profilin cDNA consists of 742 bp and
      the 375 bp open reading frame encodes a polypeptide of 125 amino acids, having a
      predicted isoelectric point of 5.87. The deduced amino acid sequence shows 42.9%
      amino acid sequence identity to the profilin of mosquito Anopheles gambiae. The
      profilin mRNA was highly expressed in hemocytes and moderately in hepatopancreas
      of normal crab. The higher expression of profilin mRNA is observed in crab
      challenged by the pathogenic bacterium Vibrio parahaemolyticus. These results
      suggest a potential role for profilin in pathogen host defense mechanisms.

PMID- 20672412
TI  - [cDNA cloning and expression characterization of three regulatory subunits of
      NADPH oxidase within cytoplasm from mandarin fish, Siniperca chuatsi].
AB  - The phagocyte NADPH oxidase plays a crucial role in host defense against invading
      microorganisms by catalyzing the formation of reactive oxygen species, which is
      the precursor of a variety of microbicidal oxidants such as hydrogen peroxide
      (H2O2). In the present study, full-length cDNAs of three regulatory subunits of
      NADPH oxidase, including p40phox, p47phox, p67phox were cloned from head kidney
      of mandarin fish utilizing the reverse transcription polymerase chain reaction
      and rapid amplification of cDNA ends. Sequence analysis showed that the full
      length cDNA of p40phox is 1 406 nt, containing a 1 050 nt open reading frames
      that encodes a 349 amino acid protein, the full length cDNA of p47phox is 1 686
      nt, containing a 1 209 nt open reading frames that encodes a 402 amino acid
      protein, the full length cDNA of p40phox is 2 185 nt, containing a 1 488 nt open
      reading frames that encodes a 495 amino acid protein. Semi-quantitative RT-PCR
      analyses from various tissues indicated that mRNAs of the three subunits can be
      detected in the blood, brain, heart, spleen, kidney and thymus, but their
      expression intensity are different in tissues. Stimulating the mandarin fish with
      formalin killed Flavobacterium columnare G4 significantly up-regulated the
      expression of p40phox in blood and head kidney; and p47phox in head kidney and
      spleen; and p67phox in blood, head kidney and spleen. The results suggested that
      mandarin NADPH oxidase was involved in the immune responses against bacteria.

PMID- 20672414
TI  - [Role of Fas/FasL on apoptosis of porcine follicular granulosa cells derived from
      isolated follicles during culture in vitro].
AB  - The whole antral follicles were isolated from porcine ovaries and classified as
      follows: healthy follicles (HF), early atretic follicles (EF) and progressed
      atretic follicles (PF). The isolated porcine follicles were used for routine
      histological section and HE staining after examination by eyesight. Morphological
      research shows that the accuracy rate of eyesight examination for HF is 92%.
      Healthy follicles were chosen for further experiment and divided into 3 groups:
      large follicles (greater than 5 mm in diameter), medium follicles (3-5 mm in
      diameter) and small follicles (less than 3 mm in diameter). All follicles were
      cultured for 8, 16 and 24 h, respectively and the apoptosis of of their granulosa
      cells were examined by Annexin V-FITC/PI double-labeling. It showed that the
      total apoptotic rate of granulosa cells derived from cultured follicles could
      reach over 70% at 8 h after culture and be 81.1% - 94.6% at 24 h after culture.
      Granulosa cells from groups were collected at 0, 8, 16, 24, 48 and 72 h after
      culture without serum and used for the examination of expression of FasL and Fas
      mRNA with real time PCR SYBRgreen method. The expression level of FasL mRNA of
      granulosa cells from different size of follicles increased with culture time and
      reached the highest level at 24 h after culture (P<0.05). Expression level of
      FasL mRNA of granulosa cells from small follicles was higher than those from
      large and medium follicles. There exists no difference for expression level of
      Fas mRNA of granulosa cells among groups before culture but significantly
      increased at 8 h after culture and reached the highest level at 48 h after
      culture. It showed in the present experiment that the follicular culture system
      without serum used could effectively induce the apoptosis of follicular granulosa
      cells. Cell apoptosis is the main cause of follicular atresia, the degree of
      which varied with the size of follicles. Small follicles seemed to be easier
      atretic than medium and large follicles.

PMID- 20672415
TI  - [Effects of cadmium on metamorphism and gonad differentiation in Rana
      chensinensis].
AB  - 200 tadpoles of Rana chensinensis at stage 26 - 27 were exposed to 0.05, 0.1, 0.2
      or 0.4 mg/L Cd2+ in tap water respectively until they're fully metamorphic after
      which the heteromorphic young frogs in different treatments were anatomized,
      females and males were identified through gonad observation, and the female ratio
      was calculated. Localization of estrogen receptors (ER) in liver cells was
      investigated in different treatments using immunocytochemistry. The results
      showed that Cd2+ might induce limb abnormality, however, there was little
      correlation between abnormality rate and cadmium concentration in lower Cd2+
      levels except for a higher limb abnormality ratio in the 0.4 mg/L group. On the
      other hand, Cd2+ could affect gonad differentiation. Compared to the control
      group, the proportion of female population increased in the 0.05 mg/L group and
      decreased in the 0.1, 0.2 and 0.4 mg/L ones. The sex rate in the 0.2 mg/L group
      is significantly different from that in the control group. Hermaphrodite gonads
      appeared in the two treatments with 0.2 mg/L and 0.4 mg/L of Cd2+. Additionally,
      ER expression was positive in both cytoplasm and nucleolus of liver cells in Cd2+
      treated groups. But, there was no linear relationship between ER expressions
      levels and the concentration of Cd2+. These results suggested that cadmium can
      influence tadpole metamorphosis and gonad development by affecting the secretion
      of sex hormone.

PMID- 20672416
TI  - [Effects of morphine on pupillary light reflex in monkeys].
AB  - The pupil size of both human and other animals can be affected by light. Many
      kinds of psychiatrical and psychological disorders, such as drug abuse, associate
      with abnormal properties of pupillary light reflex. Thus, the properties of
      pupillary light reflex could serve as an indicator for drug abuse detection.
      However, the effect of drug abuse on pupillary light reflex is till unclear. To
      assess the effects of addictive drugs on pupillary light reflex
      quantificationally, in the present study, we examined the effects of morphine on
      pupil diameter and pupillary light reflex in rhesus monkeys. By measuring the
      pupil diameter at different timing points before and after the administration of
      morphine, we found that morphine administration reduced the diameter of pupil and
      decreased the constriction rate. Our present results provide an experimental
      support for applying the properties of pupillary light reflex as a reference in
      addicts' detection.

PMID- 20672417
TI  - [A new method to explore the modulation from the saccadic system on the pupillary
      light reflex system].
AB  - The saccadic system has anatomical and functional connections with the pupillary
      light reflex (PLR) system. But it is not known whether the saccadic system
      modulates the PLR system. To investigate this issue, it is necessary to
      understand whether the uneven light stimulus to retina and the near responses
      influence the change of pupil diameter. We designed a new behavioral method to
      investigate the issue on human subjects. METHODS: one eye of the subject was
      stimulated by pulse light stimulus from a horizontal linear array of light
      emitting diodes (LEDs) presented across visual field in an ocular mask. The
      changes of the eye position and pupil diameter of another eye were recorded by an
      infrared eye tracking system. RESULTS: The relative constriction ratios of PLRs
      on the condition that the fixation points of subjects were in the nasal visual
      field were not significantly different from that the fixation points of subjects
      were in the temporal visual field(P=0.148, non-paired t test). CONCLUSION: The
      influences from uneven light stimulus to retina and the near responses were
      eliminated by this method. The method can be used to study the modulation from
      the saccadic system on the pupillary light reflex system.

PMID- 20672418
TI  - [A new record of bird species in China: black-chinned babbler (Stachyris
      pyrrhops)].

PMID- 20672419
TI  - [Sonogram structure and timing of duets of western black crested gibbon in
      Wuliang Mountain].
AB  - We studied the sonogram and timing of duets of three groups of Central Yunnan
      western black crested gibbons (Nomascus concolor jingdongensis) in Dazhaizi, Mt.
      Wuliang. The study was based on a 13-month field observation period, from March
      2003 to March 2004. A Sony TC-D5 Pro2 recorder, Sony C-76 directed microphone,
      and Sony tape were used to record the duet bouts in March 2007 and March 2008.
      Signal/RTS 4.0 was used to analyze the sonogram of the duet. We first presented
      sonograms of all kinds of sound units in the duets made by western black crested
      gibbons. The adult male could produce boom, aa notes and modulated figures. Adult
      females produced great call or abortive great call. The two adult females in each
      group usually produced great calls synchronously. After the great call, males
      always immediately produced a modulated figure to coordinate with the female. The
      interval between the modulated figure and great call was 2.7 s. On average,
      groups sang on 53% of days monitored, and sang 1.09 duet bouts per singing day.
      91.5% of the duets were produced between half an hour before and three hours
      after the sunrise. The average duration of the duets was 12.9 min, and females
      produced 4.6 great calls during one duet bout. The intervals between two
      successive great calls were generally 115 s. There was no significant difference
      in the duration and frequency of the duet bouts, but there was significant
      difference in the number of the great calls and intervals between great calls
      among groups.

PMID- 20672420
TI  - [Habitat use of Williamson's Mouse-deer (Tragulus williamsoni) in Mengla area,
      southern Yunnan].
AB  - Combining line-transect method and sampling method, the geographic coordinates of
      footprint links for Williamson's Mouse-deer (Tragulus williamsoni) were collected
      in Mengman and Longmen regions of Mengla area, southern Yunnan, from June to
      December 2007. A distribution pattern map of the mouse-deer was produced by GIS
      software. Eleven ecological factors were measured in collected and available
      samples. The results indicated that the mouse-deer preferred valleys along banks
      of rivers or streams in low altitude, and were mainly distributed in Sanchahe of
      Mengman region and Darongshu of Longmen region. Comparing nominal factors between
      collected and available samples, the results showed that the mouse-deer tended to
      inhabit middle and lower slopes and favored the plant species of Ficus hirtal,
      Baccaurea samiflora, Alpinia kwangsiensis and Phrynium capitatum. These plants
      occur along banks of rivers or streams, one of the important reasons affecting
      distribution of the mouse-deer populations. Comparing quantitative factors
      between collected and available samples, the results showed that four factors
      including tall tree coverage, shrub coverage and herb coverage, and distance to
      water, were significantly different. These four factors were key in
      discriminating collected and available samples and main factors affecting the
      habitat use of the mouse-deer. The dense shrub with taller trees could form good
      shady condition for the mouse-deer, and greatly strengthen their security. Due to
      their preference for areas near water, there were more flourishing tall trees and
      dense shrubs at valleys in low altitude, which was one of important reasons
      affecting the distribution of the mouse-deer populations massing in valleys in
      low altitude.

PMID- 20672421
TI  - [Composition and characteristics of understory bird communities in monsoon
      evergreen broadleaved forest of Mengyang, Xishuangbanna in the dry season].
AB  - Understory birds in monsoon evergreen broadleaved forest of Mengyang,
      Xishuangbanna, Yunnan were sampled using mist nets from October 2008 to March
      2009. A total of 1423 individuals of 90 species belonging to 28 families and 7
      orders were captured, among which there are 8 dominant bird species, i.e., Sliver
      breasted Broadbill (Serilophus lunatus), Brown-cheeked Fulvatta (Alcippe
      poioicephala), White-throated Bulbul (Alophoixus pallidus), Golden-spectacled
      Warbler (Seicercus burkii), White-tailed Robin (Cinclidium leucurum), Black
      breasted Thrush (Turdus dissimilis), Streak-Breasted Jungle Babbler (Pellorneum
      ruficeps), and Buff-breasted Jungle Babbler (Trichastoma tickelli). Resident
      birds, the major composition of the understory birds, accounted for 89.3 percent
      of total captures. The mean capture rate was 9.0+-3.7 individuals/(100 net-hours)
      and it differed significantly between months, highest in December 2008 (12.5+
      1.3)individuals/(100 net-hours), lowest in February 2009 (5.2+-0.6)
      individuals/(100 net-hours). The most significant characteristic of understory
      birds in Xishuangbanna is more species abundance and lower species density
      compared to understory bird composition of South China. Another characteristic is
      that no obvious dominance pattern was observed in Babbler species. We also
      noticed that silver-breasted Broadbill, National Key Protection Bird, is the most
      abundance species in our captures, thus their habitat require further protection.

PMID- 20672422
TI  - [Comparison of thermogenic character of liver and muscle in Chinese bulbul
      Pycnonotus sinensis between summer and winter].
AB  - Acclimatization to winter conditions is an essential prerequisite for survival of
      small passerines. Seasonal changes in a bird's physiology and behavior are
      considered to be part of an adaptive strategy for survival and reproductive
      success. Changes in photoperiod, ambient temperature and food availability
      trigger seasonal acclimatization in physiology and behavior of many birds. In the
      present study, seasonal adjustments in several physiological, hormonal, and
      biochemical markers were examined in wild-captured Chinese bulbuls (Pycnonotus
      sinensis) from the Zhejiang Province in China. Oxygen consumption was measured
      using the closed-circuit respirometer containing 3.6 L animal chambers. State-4
      respiration in liver and muscle mitochondria was measured at 30 degree with a
      Clark electrode. The activities of cytochrome C oxidase (COX) in liver and muscle
      were measured polarographically at 30 degree using a Clark electrode. The protein
      content of mitochondria was determined by the Folin phenol method, with bovine
      serum albumin as standard. In winter sparrows had higher body mass and basal
      metabolic rate (BMR). The contents of mitochondrial protein in liver, and state-4
      respiration and COX activity in liver and muscle increased significantly in
      winter. Circulating level of serum triiodothyronine (T3) was significantly higher
      in winter than in summer. Together, these data suggest that Chinese bulbuls
      mainly coped with cold by enhancing thermogenic capacities through increased
      activity of respiratory enzymes activities. The results support the view that
      prominent winter increases in BMR are manifestations of winter acclimatization in
      Chinese bulbuls and that seasonal variation in metabolism in bulbuls is similar
      to that in other small wintering birds.

PMID- 20672423
TI  - [New record of a bat species from China, Megaderma spasma (Linnaeus, 1758)].
AB  - One male bat was collected in a cave in Cuibi Hill (N: 21 degree 53', E: 101
      degree 18', H: 683 m a.s.l.), Menglun Town, Mengla County, Yunnan Province, on
      November 26, 2006. This bat is of medium body size, with 60.7 mm forearm and 21.4
      g body mass. Its ears are large ovals and joined medially to the forehead at
      about 15% of the height of inner margin. The tragus of each ear is slender and
      distinctly bifid. The noseleaf is simple, and the posterior noseleaf is oval with
      obtuse tip and convex sides, a significant longitudinal ridge laying middle,
      which connects to intermediate noseleaf at the base. Intermediate noseleaf
      presents triangle with a W-shaped tip. Frontal noseleaf is horseshoe shape and
      attached directly to the muzzle. The tail is absent, and the second finger of
      each wing has only one phalanx. There are no upper incisors, Pm3 and Pm3. The
      upper canine has an anterior and a large posterior basal cusps. This bat is
      identified as lesser false vampire, Megaderma spasma, which is a new record of
      China. Its external and craniodental measurements were presented and compared
      with those of M. lyra. The specimen is preserved in Guangdong Entomological
      Institute.

PMID- 20672425
TI  - Sensory systems: Back into the light.

PMID- 20672424
TI  - Ask the doctor.  My 8-year-old son was diagnosed with bipolar disorder several
      years ago.  Now a new therapist thinks the problem might be temper dysregulation
      disorder.  What is that? How is it treated?

PMID- 20672426
TI  - Spinal cord injury: The two faces of spontaneous serotonin signalling.

PMID- 20672427
TI  - Spatial awareness: In space and time.

PMID- 20672429
TI  - Repair: Chemokines show the way.

PMID- 20672428
TI  - Sensory systems: A balancing act.

PMID- 20672430
TI  - Chemosensation: Tasteless mice prefer sugar.

PMID- 20672431
TI  - Synaptic plasticity: Yin and yang.

PMID- 20672432
TI  - Thomas G. Pickering memorial issue.

PMID- 20672433
TI  - Proceedings of the 34th International Symposium on High Performance Liquid Phase
      Separations and Related Techniques. Dresden, Germany. June 28-July 2, 2009.

PMID- 20672434
TI  - [Clinical pathways in surgery].

PMID- 20672435
TI  - [Expert testimony re phosphodiesterase 5 inhibitors].

PMID- 20672436
TI  - The International Society of Electrocardiology - 1959 to 2009, and New Clinical
      Uses of the Electrocardiogram in 2010. Proceedings of a symposium.

PMID- 20672437
TI  - Chronic diarrhea in an elderly man.

PMID- 20672438
TI  - A case of selective serotonin reuptake inhibitor-induced rapid eye movement
      behavior disorder.

PMID- 20672439
TI  - Combined effect of synthetic enterocin CRL35 with cell wall, membrane-acting
      antibiotics and muranolytic enzymes against Listeria cells.
AB  - AIMS: To evaluate the inhibition effectiveness of enterocin CRL35 in combination
      with cell wall, membrane-acting antibiotics and muranolytic enzymes against the
      foodborne pathogen Listeria. METHODS AND RESULTS: Synthetic enterocin CRL35 alone
      and in combination with monensin, bacitracin, gramicidin, mutanolysin and
      lysozyme were used in this study. Minimal inhibitory concentration (MIC) and
      fractional inhibitory concentration (FIC) index assays were performed using
      Listeria innocua 7 and Listeria monocytogenes FBUNT as sensitive strains.
      Antibiotics showed positive interactions with the bacteriocin in both strains
      tested. On the other hand, when mutanolysin and enterocin CRL35 were added to
      resting cells in a buffer system, the lytic effect of mutanolysin was enhanced.
      However, the addition of mutanolysin showed no effect on the growth of L. innocua
      7 cells in a culture medium. Moreover, mutanolysin allowed the overgrowth of L.
      innocua 7 cells to an OD similar to control cells in the presence of inhibitory
      concentration of enterocin CRL35. In contrast, the combination of lysozyme and
      enterocin CRL35 resulted in a 50% inhibition of the L. innocua 7 growth.
      CONCLUSIONS: Based on our results, we conclude that the combination of synthetic
      enterocin CRL35 with some antibiotics is effective against L. innocua 7 and L.
      monocytogenes FBUNT cells, and more importantly the amount of these agents to be
      used was considerably reduced. The effectiveness of the combination of synthetic
      enterocin CRL35 with muramidases seems to depend on complex environments, and
      more detailed studies need to be performed to elucidate this issue. SIGNIFICANCE
      AND IMPACT OF THE STUDY: Enterocin CRL35 represents a promising agent that not
      only can ensure the quality and safety of food but it can also be combined with
      several antimicrobial agents important in the medical field.

PMID- 20672440
TI  - Influence of Planococcus ficus on Aspergillus section Nigri and ochratoxin A
      incidence in vineyards from Argentina.
AB  - AIM: The aim of this work was to evaluate the effect of Planococcus ficus
      infection in red wine grapes on Aspergillus section Nigri and ochratoxin A (OTA)
      contamination. METHODS AND RESULTS: During 2006/2007 and 2008/2009 vintages,
      Merlot, Malbec and Cabernet Sauvignon varieties divided into two categories of
      grape samples (undamaged and damaged by P. ficus) were evaluated. Regardless of
      the grape variety and the harvest season evaluated, Aspergillus section Nigri
      incidence and the mean OTA concentration in damaged berries were significantly
      higher than that in the undamaged ones (P < 0.05; P < 0.001). The Merlot variety
      showed the highest level of black aspergilli contamination in damaged grapes
      during the 2006/2007 vintage (53.5% of infection), whereas Malbec presented the
      highest incidence during the 2008/2009 vintage (57.6% of infection). The Cabernet
      Sauvignon variety showed the highest OTA levels, ranging from 0.1 to 140 microg
      kg(-1). CONCLUSIONS: The presence of P. ficus in vineyards increased the risk of
      OTA occurrence in grapes, suggesting the need to implement insect control at
      preharvest stage to reduce the entry of OTA in the wine production chain.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This study is the first report on the
      influence of P. ficus on the potential risk of OTA contamination in grapes.

PMID- 20672441
TI  - Optimization of selected cultivation parameters for Cordyceps guangdongensis.
AB  - AIMS: To increase the fruit body production of Cordyceps guangdongensis, selected
      cultivation conditions, especially nutritional parameters were optimized. METHODS
      AND RESULTS: Cordyceps guangdongensis was inoculated on potato dextrose agar
      slants with pH values from 4.5 to 9.0 and cultivated in artificial media with
      different carbon and nitrogen supplements. Primordium formation in C.
      guangdongensis was favoured by slightly acidic conditions. Fruit body yields and
      biological efficiency (BE) recorded were all highest in cultures of C.
      guangdongensis supplemented with sucrose and KNO3 as carbon and nitrogen
      supplements, respectively. Highest fruit body yields and BE values were recorded
      with C : N ratio of 12 : 1. The optimal medium consisted of (g l(-1)) 20.0
      sucrose, 4.0 soya bean powder, 5.0 beef extract and 10.0 KNO3. Cultivation
      experiments using this medium confirmed its reliability; 18.35% of BE was
      obtained, compared with a calculated maximum BE of 18.65% based on orthogonal
      test data. CONCLUSIONS: Cordyceps guangdongensis preferred sucrose and potassium
      nitrate as best carbon and nitrogen supplements. It produced satisfying yield of
      fruit body with optimized medium. SIGNIFICANCE AND IMPACT OF THE STUDY: Optimized
      artificial cultivation conditions could promote the yield of C. guangdongensis
      and decreased the cost of production.

PMID- 20672442
TI  - General medicine and  surgery for dental practitioners.  Part 6--Cancer,
      radiotherapy  and chemotherapy.
AB  - Dental practitioners will encounter patients who have been affected by cancer or
      who are current cancer patients. Dentists play an important role in the overall
      healthcare of such patients, particularly in those with head and neck malignancy.
      This paper gives an overview of the impact of cancer and its treatment on dental
      management.

PMID- 20672443
TI  - Protein expression profiling of mouse thymoma cells upon exposure to the
      trichothecene deoxynivalenol (DON): implications for its mechanism of action.
AB  - The objective of this work was to investigate whether proteomic analysis of
      thymoma cells treated with the trichothecene deoxynivalenol (DON) as compared to
      non-treated (control) cells would reveal differential protein expression, and
      thus would contribute to a better understanding of the mechanisms of its
      toxicity. For that purpose the mouse thymoma cell line EL4 was exposed to 0.5
      microM DON for 6 hr. A total of 30 proteins were affected after exposure of EL4
      cells to DON. Most of these proteins were up-regulated and included key metabolic
      enzymes (e.g., fatty acid synthase, aldose reductase, carbamoyl phosphate
      synthetase, glucose-6-phosphate isomerase), chaperones (e.g., HSP9AB1 and HSP70),
      enzymes implicated in protein folding (PDI and ERO1-l alpha), and proteins
      involved in protein degradation (ubiquitin-conjugating enzyme (E1) and proteasome
      subunit alpha type-1). In addition, an IgE-binding protein with a molecular
      weight of 60 kDa and My-binding protein 1a (MYBBP1A), a transcription factor,
      were found to be up-regulated by DON. The observed up-regulation of MYBBP1A, a
      known repressor of a number of transcription factors such as PGC-1 alpha, C-myb,
      and p65 of the NF-kappaB family, suggests that this protein might play a role in
      the mechanism of DON toxicity.

PMID- 20672444
TI  - What will they think of next? Parthenogenesis and the remarkable insight derived
      from biological variation.

PMID- 20672445
TI  - Proceedings of the 3rd Veterinary Herpesvirus Symposium of the European Society
      for Veterinary Virology.

PMID- 20672446
TI  - Cell polarity: ASPP2 gets a polarity complex.

PMID- 20672448
TI  - Tenofovir-linked hyperparathyroidism is independently associated with the
      presence of vitamin D deficiency.
AB  - BACKGROUND: To determine patient and treatment characteristics associated with
      vitamin D deficiency (VDD) in an UK inner city HIV-1-positive adult cohort.
      METHODS: Two hundred twenty-seven HIV-positive patients attending prospectively
      for routine blood tests in winter had serum 25-hydroxyvitamin D and parathyroid
      hormone (PTH) concentrations and other routine chemistry measured. Those with and
      without VDD were defined as having serum 25-hydroxyvitamin D concentrations <50
      nmol/L and >75 nmol/L, respectively. Characteristics were compared between
      patients with and without VDD. The effects of VDD, tenofovir use, and their
      interaction on chemical measures were investigated. RESULTS: VDD was found in 57%
      (131 of 227) of patients. Independent associations included nonwhite ethnicity
      [adjusted odds ratio (95% confidence interval): 7.40 (2.52 to 21.7)], higher
      random blood glucose [2.38 (1.24 to 4.57) per mmol/L], higher estimated
      glomerular filtration rate [eGFR: 1.04 (1.01 to 1.06)], and higher PTH [1.19
      (1.00 to 1.42)]. PTH was higher in those receiving tenofovir (median 7.2 pmol/L)
      than other patients (4.3; P < 0.001) overall, but high PTH with tenofovir
      occurred only in the context of VDD. Tenofovir use was not associated with serum
      creatinine or eGFR overall but interacted with vitamin D status (P = 0.05 and P =
      0.08, respectively), being linked to somewhat higher creatinine and lower eGFR
      among patients without VDD but higher eGFR in VDD patients. CONCLUSIONS: 25(OH)
      VDD is associated with tenofovir-linked hyperparathyroidism and also with higher
      eGFR.

PMID- 20672449
TI  - [The first and the last will become the best].

PMID- 20672447
TI  - Three-year safety and efficacy of vicriviroc, a CCR5 antagonist, in HIV-1
      infected treatment-experienced patients.
AB  - BACKGROUND: Vicriviroc, an investigational CCR5 antagonist, demonstrated short
      term safety and antiretroviral activity. METHODS: Phase 2, double-blind,
      randomized study of vicriviroc in treatment-experienced subjects with CCR5-using
      HIV-1. Vicriviroc (5, 10, or 15 mg) or placebo was added to a failing regimen
      with optimization of background antiretroviral medications at day 14. Subjects
      experiencing virologic failure and subjects completing 48 weeks were offered open
      label vicriviroc. RESULTS: One hundred eighteen subjects were randomized.
      Virologic failure (<1 log10 decline in HIV-1 RNA > or =16 weeks
      postrandomization) occurred by week 48 in 24 of 28 (86%), 12 of 30 (40%), 8 of 30
      (27%), 10 of 30 (33%) of subjects randomized to placebo, 5, 10, and 15 mg,
      respectively. Overall, 113 subjects received vicriviroc at randomization or after
      virologic failure, and 52 (46%) achieved HIV-1 RNA <50 copies per milliliter
      within 24 weeks. Through 3 years, 49% of those achieving suppression did not
      experience confirmed viral rebound. Dual or mixed-tropic HIV-1 was detected in 33
      (29%). Vicriviroc resistance (progressive decrease in maximal percentage
      inhibition on phenotypic testing) was detected in 6 subjects. Nine subjects
      discontinued vicriviroc due to adverse events. CONCLUSIONS: Vicriviroc seems safe
      and demonstrates sustained virologic suppression through 3 years of follow-up.
      Further trials of vicriviroc will establish its clinical utility for the
      treatment of HIV-1 infection.

PMID- 20672450
TI  - Pharmacokinetic interactions between buprenorphine/naloxone and once-daily
      lopinavir/ritonavir.
AB  - BACKGROUND: This study was conducted to examine the pharmacokinetic interactions
      between buprenorphine/naloxone (BUP/NLX) and lopinavir/ritonavir (LPV/r) in HIV
      seronegative subjects chronically maintained on BUP/NLX. METHODS: This study was
      an open labeled pharmacokinetic study in twelve HIV-seronegative subjects
      stabilized on at least 3 weeks of BUP/NLX therapy. Subjects sequentially
      underwent baseline and steady-state pharmacokinetic evaluation of once-daily
      LPV/r (800/200 mg). RESULTS: Compared to baseline values, BUP AUC0-24h (46.8 vs.
      46.2 ng*hr/mL) and Cmax (6.54 vs. 5.88 ng/mL) did not differ significantly after
      achieving steady-state LPV/r. Similar analyses of norBUP, the primary metabolite
      of BUP, demonstrated no significant difference in norBUP AUC0-24 hours (73.7 vs.
      52.7 ng x h/mL); however, Cmax (5.29 vs. 3.11 ng/mL) levels were statistically
      different (P < 0.05) after LPV/r administration. Naloxone concentrations were
      similarly unchanged for AUC0-24 hours (0.421 vs. 0.374 ng x hr/mL) and Cmax
      (0.186 vs. 0.186 ng/mL). Using standardized measures, no objective opioid
      withdrawal was observed. The AUC0-24 hours and Cmin of LPV in this study did not
      significantly differ from historical controls (159.6 vs. 171.3 microg x hr/mL)
      and (2.3 vs. 1.3 microg/mL). CONCLUSIONS: The addition of LPV/r to stabilized
      patients receiving BUP/NLX did not affect buprenorphine pharmacokinetics but did
      increase the clearance of norbuprenorphine. Pharmacodynamic responses indicate
      that the altered norbuprenorphine clearance did not lead to opioid withdrawal.
      Buprenorphine/naloxone and LPV/r can be safely coadministered without need for
      dosage modification.

PMID- 20672452
TI  - For urgent and emergent cases, which one goes to the OR first?

PMID- 20672453
TI  - Alone in a crowd.

PMID- 20672454
TI  - Aspects of human disease. Case 50. Eating disorders.

PMID- 20672451
TI  - Addition of 7 days of zidovudine plus lamivudine to peripartum single-dose
      nevirapine effectively reduces nevirapine resistance postpartum in HIV-infected
      mothers in Malawi.
AB  - BACKGROUND: We assessed whether 7 days of zidovudine + lamivudine postpartum with
      single-dose nevirapine at labor decreases nevirapine resistance in HIV-infected
      women in Malawi. METHODS: HIV-infected pregnant women receiving intrapartum
      single-dose nevirapine and 7 days of zidovudine + lamivudine (n = 132) and women
      receiving intrapartum single-dose nevirapine alone (n = 66) were followed from an
      antenatal visit through 6 weeks postpartum. Plasma specimens at 2 and 6 weeks
      postpartum were tested for genotypic resistance to nevirapine by population
      sequencing and sensitive real-time polymerase chain reaction. Poisson regression
      was used to determine predictors of postpartum nevirapine resistance. RESULTS:
      Median HIV RNA was similar at entry (4.27 log vs. 4.35 log, P = 0.87), differed
      at 2 weeks postpartum (2.67 log vs. 3.58 log, P < 0.0001) but not at 6 weeks
      postpartum (4.49 log vs. 4.40 log, P = 0.79), between single-dose
      nevirapine/zidovudine + lamivudine and single-dose nevirapine groups,
      respectively. Nevirapine resistance, measured by population sequencing and
      sensitive real-time polymerase chain reaction, was significantly less common in
      those receiving single-dose nevirapine/zidovudine + lamivudine compared with
      single-dose nevirapine, respectively, at 2 weeks [10% (4 of 40) vs. 74% (31 of
      42), P < 0.0001] and 6 weeks postpartum [10% (11 of 115) vs. 64% (41 of 64), P <
      0.0001; adjusted relative risk = 0.18, 95% confidence interval (0.10 to 0.34)].
      CONCLUSIONS: The significant decrease in nevirapine resistance conferred by 1
      week of zidovudine + lamivudine should help policymakers optimize peripartum HIV
      prophylaxis recommendations.

PMID- 20672455
TI  - Baccalaureate.

PMID- 20672456
TI  - Risky business.

PMID- 20672457
TI  - Risky business.

PMID- 20672458
TI  - Risky business.

PMID- 20672459
TI  - Risky business.

PMID- 20672460
TI  - Case study. Conflicting beliefs. Commentary.

PMID- 20672462
TI  - Metaphors in our mouths: the silencing of the psychiatric patient.

PMID- 20672463
TI  - New strategies for the control of inflammatory diseases: type I interferon in
      human pathology. Proceedings of a symposium. March 27, 2009. Brescia, Italy.

PMID- 20672461
TI  - Case study. Conflicting beliefs. Commentary.

PMID- 20672464
TI  - Recent-onset ulcerative colitis complicated by colon ischemia in an elderly
      patient.

PMID- 20672465
TI  - Effects of testosterone in older men with mild-to-moderate cognitive impairment.

PMID- 20672466
TI  - A 65-year-old woman with self-injurious behavior: a case report.

PMID- 20672468
TI  - Commemorating the future in post-war Chernivtsi.
AB  - Throughout the Second World War and the post-war period, the city of Chernivtsi
      was transformed from a multiethnic and borderland urban microcosm into a
      culturally uniform Soviet socialist city. As the Soviets finally took power in
      this onetime capital of a Hapsburg province in 1944, they not only sponsored
      further large-scale population transfers but also "repopulated" its history,
      creating a new urban myth of cultural uniformity. This article examines the
      connection between war commemoration in Chernivtsi in the era of post-war, state
      sponsored anti-Semitism and the formation of collective memory and identities of
      the city's post-war population. The images of homogeneously Ukrainian Chernivtsi
      and Bukovina were created through the art of monumental propaganda, promoting
      public remembrance of certain events and personalities while making sure that
      others were doomed to oblivion. Selective commemoration of the wartime events was
      an important tool of drawing the borders of Ukrainian national identity, making
      it exclusivist and ethnic-based. Through an investigation of the origins of the
      post-war collective memory in the region, this article addresses the problem of
      perceived discontinuity between all things Soviet and post-Soviet in Ukraine. It
      demonstrates that it is, on the contrary, the continuity between Soviet and post
      Soviet eras that defines today's dominant culture and state ideology in Ukraine
      and particularly in its borderlands.

PMID- 20672471
TI  - (Re)making space for kiwi: beyond "fortress conservation" in Northland.
AB  - Mainstream conservation has been long dominated globally by the protected area
      paradigm. This approach has been widely challenged in recent years, and new
      conservation initiatives have emerged. The situation is mirrored in New Zealand,
      where ongoing biodiversity loss has prompted reappraisal. Within this context, we
      highlight the plight of kiwi, focusing on Northland and efforts there to (re)make
      space for this iconic bird which is at risk of extinction. While the state has
      primarily responded by fortifying "islands" on public conservation land, Far
      North communities are working in a variety of ways and localities, both within
      and beyond "the fortress", to secure a future for the "people's bird".

PMID- 20672472
TI  - Fish and boats: fisheries management issues in Northland.
AB  - New Zealand fisheries management has been the focus of a great deal of research,
      largely because of the early, and very successful, introduction of a neoliberal
      property regime in the country's commercial fisheries. Less attention has been
      paid to the other management activities of New Zealand's Ministry of Fisheries.
      This paper outlines the fisheries management issues arising over the last decade
      in the region to the north of Auckland and the practices of the Ministry as it
      worked to address them.

PMID- 20672473
TI  - Professional misconduct - not guilty (Med07/65D).

PMID- 20672474
TI  - Antiviral immunity: SCS macrophages protect the CNS.

PMID- 20672475
TI  - Mucosal immunology: Bait for MAIT cells identified.

PMID- 20672476
TI  - Inflammation: The fat controller.

PMID- 20672477
TI  - B cell responses: Plasmablasts walk the line.

PMID- 20672478
TI  - Mucosal immunology: Germ and gene tag team.

PMID- 20672479
TI  - Food rationing and the black market in France (1940-1944).
AB  - French food rationing was more stringent than that of any other Occupied country
      in Western Europe in the Second World War, and the nation's resulting aversion to
      a regime that controlled rations and prices would increase the difficulties of
      post-war governments. This article investigates the role of French state
      management in wartime food shortages, assessing the parts played by French policy
      and German interference in the food shortages, the diversion of supplies to the
      black market and the inequities in distribution. It finds the French rationing
      administration to have been poorly organized, but attributes significant
      responsibility to the German Occupation authorities, whose interference increased
      the rationing system's dysfunction. French consumers blamed the French state for
      the problems and relied increasingly on alternate means to supplement inadequate
      rations. The result was a rationing system that delivered malnourishment, social
      division and hostility to state management of the food supply.

PMID- 20672480
TI  - Punishing the mad bomber: questions of moral responsibility in the trials of
      French anarchist terrorists, 1886-1897.
AB  - In late nineteenth-century France, several criminologists maintained that the
      perpetrators of the contemporary wave of anarchist terrorism were victims of
      mental disorders who deserved judicial leniency. French courts did not accept
      this theory, but instead declared the principal terrorists sane and fully
      responsible for their crimes and, based on this view, handed down severe
      sentences. Many criminologists accused the jurists of deliberately ignoring the
      mental illness of the anarchists because of government and public pressures to
      impose the death penalty, but evidence from the anarchist trials fails to support
      this charge. The controversy highlights the conflicts between the judicial
      establishment and the emerging discipline of criminology, whose pathological
      explanations of anarchist terrorism reflected a positivist attack on the
      traditional concepts of free will and moral responsibility, concepts the jurists
      viewed as fundamental to the legal system.

PMID- 20672481
TI  - Translation de domicile: rethinking sedentarity and mobility in the early modern
      French countryside.
AB  - Was the countryside of early modern France marked fundamentally by mobility or
      sedentarity? Tax rolls suggest the former, high endogamy rates the latter. For
      the period 1660-1720, a rarely used source, the registers of translation de
      domicile (change of tax domicile), provide a more comprehensive answer than civil
      or tax records. They suggest that, first, 60,000-70,000 better-off families moved
      each year; second, poor migrants, such as day labourers, rarely made
      declarations; third, those who owned land, moved far less often; fourth,
      laboureurs typically moved between 10 and 40 kilometres to take on farms of
      greater importance; fifth, cottagers and day labourers moved to a nearby village,
      rarely more than 5 kilometres away and finally, men and their families moved for
      economic gain, whereas women moved because of economic loss, after the death of
      their husband. Because the laboureurs dominated the villages-for example, paying
      most of the taxes-their movement shook the village in fundamental ways. The
      translation de domicile registers indicate villages open to the outside, full of
      in-migrants, whose economic status often bore a close correlation to the distance
      of their move (high-long, low-short).

PMID- 20672482
TI  - Algerian orphans and colonial Christianity in Algeria, 1866-1939.
AB  - This article considers the exceptional fate of the orphan survivors of the great
      Algerian demographic crisis of the late 1860s who subsequently converted to
      Catholicism. Using a prosopographical approach, this study seeks to highlight the
      complexities of national identity in France and to explore some of the racial
      tensions emerging in Algeria in the late nineteenth century.

PMID- 20672483
TI  - Understanding household limitation strategies among the sixteenth-century urban
      poor in France.
AB  - This essay explores what we can learn about the household limitation behaviour
      and strategies of those members of sixteenth-century French society who numbered
      among the mass of the poor. In particular, it focuses on the evidence produced by
      urban poor relief councils and hospitals, as they recorded the circumstances of
      the poverty-stricken clientele for their administrative records, and presents
      some preliminary findings. Although contraceptive methods do not feature
      explicitly in petitions and supporting documents, it is possible to build up a
      modest picture from these sources of the kinds of household limitation techniques
      available to the urban poor. As this essay demonstrates, in some cases, these
      involved reproductive strategies, yet in other cases it may be more appropriate
      to speak of household limitation methods.

PMID- 20672484
TI  - In Praise of Modest Men: self-display and self-effacement in nineteenth-century
      France.
AB  - Nineteenth-century France underwent a process of individuation, or self
      affirmation, that was at once political (elections), socio-economic (market
      forces and social promotion), and cultural (autobiographical writings). While
      some contemporaries embraced this evolution and others rejected it, numerous
      individuals sought to enjoy its benefits while shielding French society from the
      threat of ambition and dissolution. Many male elites, this article argues, did so
      through a prescriptive and self-referential language of modesty. Indebted to
      ancient Christian and secular vocabularies, modesty acquired a new resonance as
      compensation for aspirations and lifestyles that could prove both seductive and
      distressing. This article focuses on provincial learned societies, speeches given
      at school awards ceremonies, and the career of celebrated doctor Jean-Louis
      Alibert. At every juncture, it finds individuals who employed an idiom of modesty
      when speaking of themselves, fellow elites, or workers and peasants. Vis-a-vis
      themselves, they sought less to erase individuation than to make it socially
      innocuous and conceptually pleasing. Their twin aspirations to self-affirmation
      and self-effacement capture a broader effort to resolve contradictions between,
      on the one hand, individual merit, initiative and opportunity and, on the other,
      equality, duty and community.

PMID- 20672485
TI  - The Ordre des medecins and the Jews in Vichy France, 1940-1944.
AB  - This paper examines the way in which the Jewish question was handled by the Ordre
      des Medecins, a representative institution for the medical profession created by
      the Vichy government. It discusses the historiography of Vichy anti-Semitism
      generally and goes on to analyze the background of anti-Semitism in the French
      medical profession in the 1930s, comparing it with anti-Semitism in other
      professions such as Law. The paper then discusses the reactions of the Ordre des
      Medecins and its governing body, the Conseil Superieur, to the Vichy anti-Semitic
      legislation which affected the profession and compares its brand of anti-Semitism
      with the official Vichy policy. It focuses on the unequal battle between the
      Conseil Superieur, whose members were typically traditional nationalistic and
      protectionist anti-Semites, and the Vichy government, where quasi-racial anti
      Semitism was official policy. It explains the inevitable defeat of the Conseil
      Superieur.

PMID- 20672486
TI  - Agrarian reform and ecological change during the Ancien regime: land clearance,
      peasants and viticulture in the province of Languedoc.
AB  - The legende noire of the French Revolution has been the underlying paradigm of
      much modern French environmental history. This legend contends that peasants were
      reckless land clearers and tree cutters who disregarded the environment and
      unleashed an unmitigated natural disaster in the countryside. But the legend is
      misconceived in many ways. The purpose of this article is to investigate Ancien
      Regime land-clearance legislation in a non-forested region of France: Lower
      Languedoc. The results of this land-clearance demonstrate that far from being
      culpable, the rural masses were officially encouraged to clear and cultivate land
      on the eve of the Revolution. The French peasantry were not as destructive as the
      legende noire suggests; the crops they chose to plant on their newly cleared
      plots reflected a sensitivity towards the environment. Vines were planted on much
      of the new land-viticulture was not only a sound ecological choice, well-suited
      to the landscape, but was also attuned to the economic realities of the day.

PMID- 20672487
TI  - Poverty, gender and incarceration in sixteenth-century Paris.
AB  - The experience of prison remains a relatively little-studied aspect of late
      medieval and early-modern criminalization of the activities of the poor. This
      study examines how poverty and gender influenced incarceration practices,
      treatment and release in sixteenth-century Paris. A study of the archives of the
      ecclesiastical gaol at Saint-Germain-des-Pres from 1537 to 1579 suggests that
      both poverty and gender affected the crimes for which women and men were
      imprisoned, the length of time they remained in detention and the reasons for
      their release.

PMID- 20672489
TI  - Traditional virtues, feudal ties and Royal Guards: the culture of service in the
      eighteenth-century "Maison Militaire du Roi".
AB  - Recent discussions of French army reform before the Revolution have revived
      interest in the more general topic of military culture in the ancien regime. One
      account of this period speaks of an evolution in criteria for military merit, one
      in which professional efficiency came to overshadow traditional martial virtues,
      such as fidelity and courage. But a review of the evidence, both archival and
      published, from the Maison militaire du Roi reveals that here, at least, old
      virtues continued to be central until the end, serving as expressions of a
      relationship with the king in which royal graces were their natural complement.
      Viewed historically, this conception of service continued a feudal tradition. The
      milieu of the Maison was distinctive in the encouragement it gave to such
      traditions, but the function of the institution as a pepiniere of officers for
      the army gave it a potentially wide influence in balancing the tendencies towards
      professionalism.

PMID- 20672490
TI  - Guest editors' introduction: Digital human faces: From creation to emotion.
AB  - This special issue presents five articles covering a variety of computer graphics
      and embodied-conversational-agent applications related to digital human faces.

PMID- 20672491
TI  - Fourth European conference on protective clothing.

PMID- 20672492
TI  - Evaluation of intractable epilepsy. Invasive monitoring.
AB  - Accurate localization of the epileptogenic zone is the fundamental key factor for
      successful epilepsy surgery. Despite the progress achieved in the field of
      neuroimaging, invasive intracranial recording is still the gold standard that
      helps recognize the patient population who may profit from surgery. Meticulous
      implantation of intracranial electrodes and judicious interpretation of their
      data is a definite need in a successful epilepsy program. Few centers in the Arab
      world are in that domain. Moreover, the society itself is not well informed to
      appreciate the potentials of surgical treatment of seizure disorders. In this
      review article, we will go over various types of intracranial recordings,
      discussing their indications, and the last updates for each. Some of the cases
      carried out at the American University of Beirut Medical Center, Beirut, Lebanon
      will be illustrated as examples of our current practice. Then, the future of
      epilepsy monitoring will be highlighted in brief.

PMID- 20672493
TI  - Subtype of hypertension is evidence for preclinical atherosclerosis. A study of
      carotid artery ultrasonography and biochemical markers.
AB  - OBJECTIVES: To assess subclinical atherosclerosis in subtypes of hypertension
      using lipid profile as a biomarker and B mode ultrasonography of the carotid
      arteries. METHODS: Ninety-six subjects (49 females and 47 males) aged 42-78 years
      were recruited from the vascular Doppler unit at Baghdad Teaching Hospital,
      Baghdad, Iraq from January to June 2008. They were grouped into normotensive
      (group I), isolated systolic hypertension (group II), isolated diastolic
      hypertension (group III), and combined systolic and diastolic hypertension (group
      IV). RESULTS: Subclinical atherosclerosis was observed in groups III and IV in
      terms of significantly low levels of high-density lipoprotein, high levels of low
      density lipoprotein, and high atherogenic index. The mean intima media thickness
      was significantly increased with transition from group I to group IV in all
      carotid arteries, and the mean resistive index value of each carotid artery in
      group IV was significantly higher than that of group I. Carotid plaque was
      demonstrated in a significantly higher percent in group IV (12 out of 15)
      followed by groups III (14 out of 31) and II (1 out of 30). CONCLUSION: Lipid
      profile and high resolution B-mode ultrasonography of the carotids are good
      predictive measures of subclinical atherosclerosis. Isolated diastolic
      hypertension and combined systolic-diastolic hypertension accounts for early
      subclinical atherosclerosis compared with isolated systolic hypertension.

PMID- 20672494
TI  - Effect of non-steroidal anti-inflammatory drugs on behavioral actions of diazepam
      in mice.
AB  - OBJECTIVE: To investigate pharmacological interactions of diazepam with non
      steroidal anti-inflammatory drugs. METHODS: Non selective cyclooxygenase enzyme
      inhibitors (100 mg/kg acetylsalicylic acid, 10 mg/kg inhibitors (100 mg/kg
      acetylsalicylic acid, 10 mg/kg indomethacin, and 10 mg/kg diclofenac), a
      selective cyclooxygnase-1 inhibitor (10 mg/kg acetylsalicylic acid), and a
      selective cyclooxygnase-2 inhibitor (10 mg/kg celecoxib) of non steroidal anti
      inflammatory drugs were individually pretreated to 15 and 24 groups of Albino
      mice for dose and time dependent models (n = 8, each treatment) before sleeping
      induced by diazepam (20 mg/kg, intraperitoneally). In 6 groups using an open
      field and 4 groups using traction test models (n = 10), 5 and 10 mg/kg of
      diazepam, intraperitoneally were given to induce sedation and muscle relaxation,
      and 2 mg/kg to induce anxiolytic action after treatment with acetylsalicylic acid
      (10 mg/kg) to 4 groups (n = 6). This study was carried out at the Al-Fateh
      Medical Science University, Tripoli, Libya between February and May 2009.
      RESULTS: In dose and time dependent models non selective cyclooxygenase and
      selective cyclooxygnase-1 inhibitors significantly reduced the duration of sleep
      induced by diazepam in mice by 60-75%, while the selective cyclooxygnase-2
      inhibitor did not (p > 0.05). However, anxiolytic, muscle relaxant, and sedative
      effects of diazepam were unchanged by acetylsalicylic acid. CONCLUSION: Non
      steroidal anti-inflammatory drugs, most likely cyclooxygenase selective-1
      inhibitors reduced the duration of sleep induced by diazepam, and this
      interaction could be of a pharmacodynamic type.

PMID- 20672495
TI  - Evaluation of neurogenic dysphagia in Iraqi patients with acute stroke.
AB  - OBJECTIVES: To clinically assess neurogenic dysphagia, and to correlate its
      presence with demographic features, different stroke risk factors, anatomical
      arterial territorial stroke types, and pathological stroke types. METHODS:
      Seventy-two stroke inpatients were studied between July 2007 and February 2008,
      at the Departments of Medicine and Neurology at Al-Yarmouk Teaching Hospital,
      Baghdad, and Rizgary Teaching Hospital, Erbil, Iraq. All patients were assessed
      using the Mann Assessment of Swallowing Ability score (MASA), Modified Rankin
      Scale, and the Stroke Risk Scorecard. All patients were reassessed after one
      month. RESULTS: There were 40 males and 32 females. Sixty-eight patients had
      ischemic stroke, and 4 had primary intracerebral hemorrhage (ICH). According to
      the MASA score, 55% of anterior circulation stroke (ACS) cases were associated
      with dysphasia, and 91% of lateral medullary syndrome cases were associated with
      dysphagia. Fifty-six percent of ACS dysphagic cases improved within the first
      month. Forty percent of dysphagic patients died in the one month follow up
      period, and in most, death was caused by aspiration pneumonia. We observed no
      significant differences regarding demographic features of dysphagia. CONCLUSION:
      Dysphagia can be an indicator of the severity of stroke causing higher mortality
      and morbidity in affected patients. It was not related to the stroke risk factors
      and the type of stroke. It is essential from a prognostic point of view to assess
      swallowing, and to treat its complications early.

PMID- 20672496
TI  - Autism and parents' education. New data from the developing world.
AB  - OBJECTIVES: To investigate the link between autism disorders and engineering
      training of parents. METHODS: All Autistic-Pervasive Developmental Disorders
      (PDD) children that were diagnosed on the bases of the Diagnostic and Statistical
      Manual for Mental Disorders (DSM-IV), and met the required criteria for autism,
      over a defined period (March 2006 to June 2007) were included. We then took all
      non-PDD developmental disorders cases seen during the same time frame as the
      autistic children as a control; these included speech delay, mental retardation,
      and Down's syndrome. Our data covered demographic data, parents and grandparents'
      education, and profession. Parents' education/professions were classified into 2
      groups only, 1-engineering or mathematician; and 2-humanities, neither
      engineering nor math. The children were divided into 2 groups, autism (57 cases),
      and developmental disorders (40 cases). RESULTS: Regarding the main question of
      this study (hypothesized engineering link), the data showed some differences
      between the 2 groups (x2 = 2.503, degrees of freedom [df] = 1; p = 0.093), but
      not of major significance. There was no significant difference (x2 = 0.370; df =
      2; p = 0.831) between the 2 groups on the variable of consanguinity. CONCLUSION:
      We have found that the Saudi Arabian sample, though relatively small, has
      considerable similarities with both the UK and USA data. There is a possibility
      of an association between autism and the engineering/math training of fathers.
      The implication is briefly discussed.

PMID- 20672497
TI  - Computed tomography based measurement of the dimensions of foramen ovale and
      rotundum in trigeminal neuralgia.
AB  - OBJECTIVES: To compare sizes of the foramen ovale and rotundum in trigeminal
      neuralgia (TN) patients and healthy individuals on CT images. METHODS: Twenty-one
      TN patients and 24 healthy volunteers were included in this retrospectively
      designed study, carried out at the Department of Anatomy, Medical School,
      Gaziantep University, Gaziantep, Turkey, between May 2004 and August 2009. The
      dimension of the foramen ovale on the cross-sectional images, and the foramen
      rotundum on coronal sections on CT images were examined. RESULTS: The mean sizes
      of the foramen rotundum on the right and left sides were 3.04 x 3.2 mm and 2.8 x
      2.9 mm in TN patients, and 2.4 x 3.2 mm and 2.5 x 3.1 mm in controls. The mean
      sizes of the foramen ovale on the right and left sides were 4.8 x 6.04 mm and 4.9
      x 5.5 mm in TN patients, and 3.7 x 8.2 mm and 4.1 x 7.6 mm in controls. The
      dimensions of left and right foramens were not significantly different in both TN
      patients and controls (p > 0.05). Furthermore, a statistically significant
      difference was not found between the foraminal dimensions of the TN patients and
      controls (p > 0.05). CONCLUSION: This study revealed that the sizes of foramen
      ovale and rotundum are highly symmetrical in both groups, suggesting that sizes
      of the foramina are not associated with the occurrence of TN.

PMID- 20672498
TI  - Brain computed tomography in patients with syncope.
AB  - OBJECTIVE: To determine the use of brain CT as a routine diagnostic tool in
      patients presenting with syncope. METHODS: From March 2006 to April 2008, 292
      patients presented with a history of transient loss of consciousness to the
      emergency department at the King Hussein Medical Center, Amman, Jordan. A
      neurologist examined all investigated patients and brain scans were obtained.
      Patients were classified into 4 groups according to brain scan findings and their
      neurological examination. RESULTS: Out of the 292 patients, 254 (86.9%) patients
      underwent brain scan, 38 (13%) patients were excluded. The first group included
      203 (79.9%) patients, who had normal brain scan, and normal neurological
      examination. The second group included 10 (3.9%) patients all of which had
      abnormal brain CT scan findings related to their syncope, and also had abnormal
      neurological examination. The abnormal neurological findings can be attributed to
      their syncopal episode and abnormal brain CT findings. Classified into 3 groups
      based on their brain CT findings and their neurological examination on
      presentation. The third group included 39 (15.3%) patients who had abnormal brain
      scan with findings not related to their syncope and either normal or abnormal
      neurological examination not related and cannot be attributed to the abnormal
      head CT findings and their syncopal episode. The last group had 2 patients (0.7%)
      with abnormal scan and normal neurological examination. CONCLUSION: The use of
      brain scan as a routine diagnostic tool in patients with syncope is
      unjustifiable, unless there is an indication in the history or physical
      examination.

PMID- 20672499
TI  - Insomnia treatment by olanzapine. Is sleep state misperception a psychotic
      disorder?
AB  - Offering a new perspective on sleep state misperception, we discuss a patient who
      presented with sleep state misperception and was ultimately diagnosed with
      delusional disorder. A 60-year-old woman with chief complaints of insomnia,
      agitation, and suicidal ideation, was admitted to an inpatient psychiatric ward.
      Based on information from her family and a mental state examination, her primary
      diagnosis was sleep state misperception. She was treated with Trazodone. Because
      she was unresponsive to the treatment, a full psychiatric evaluation and wrist
      actigraphy report were undertaken, resulting in a revised diagnosis of delusional
      disorder. She was started on Olanzapine and, after 6 weeks was discharged with
      good improvement. Sleep state misperception might be considered not just as a
      sleep disorder, but also as a psychiatric disorder with psychotic symptoms.
      Further research is recommended.

PMID- 20672500
TI  - Cognitive and behavioral development profile of a Saudi girl with Fragile X
      syndrome.
AB  - This report presents an ideal case of a girl with Fragile X syndrome. There is
      positive family history of the same condition. The analysis revealed low average
      IQ with attention deficit, shyness, and social withdrawal. The report shows that
      girls with Fragile X might have only mild cognitive deficits that enable them to
      adapt and succeed in society.

PMID- 20672501
TI  - Neurosarcoidosis presenting with persistent vomiting.
AB  - Sarcoidosis is a multi-system granulomatous disease of unknown etiology. It
      mainly affects the lungs more than other organs, but liver, skin, lymph nodes,
      and nervous system can be involved. The last is referred to as neurosarcoidosis
      with a wide range of clinical manifestations depending on the area of the nervous
      system involved. The differential diagnosis is wide, and the diagnosis, which is
      based on the histopathology, is sometimes difficult to confirm. Magnetic
      resonance imaging is the imaging modality of choice for establishing CNS
      involvement along with the clinical presentation. Cerebrospinal fluid analysis is
      indicative of the disease activity. We report a 39-year-old man of Indian origin
      who presented with persistent vomiting for over 2 years due to hypopituitarism
      and active neurosarcoidosis.

PMID- 20672502
TI  - Syphilitic arteritis involving the origin of the cervical internal carotid
      artery.
AB  - We report a case of meningovascular syphilis in a young adult woman presenting
      with left hemiparesis due to near occlusion of proximal cervical internal carotid
      with subacute middle cerebral artery territory infarction. Diagnosis was made on
      the basis of positive serum, and spinal fluid serology for syphilis, carotid
      Doppler, and magnetic resonance angiography, as well as improvement after
      intravenous penicillin therapy. In this case report, the imaging findings were
      described and related literature was reviewed.

PMID- 20672503
TI  - Subependymoma of the spine.
AB  - Subependymoma is a rare benign CNS tumor (WHO grade I). The common sites of
      origin for this type of tumor are the lateral and the fourth ventricles. A spinal
      intramedullary location is rare. Radiological features of intramedullary
      subependymoma can mimic more common and more aggressive tumor types. We report a
      case of a 61-year-old male who presented with a 3-year history of low back pain,
      associated with right lower limb progressive weakness and sensory numbness. An
      MRI of the lumbar spine revealed an intradural intramedullary lesion extending
      from the level of T10-L1. Clinical presentation, radiological, and pathological
      studies of this case of subependymoma are presented. The incidence of spinal
      subependymoma was also discussed in light of a literature review.

PMID- 20672504
TI  - Disseminated tuberculosis complicated with tuberculous meningitis, miliary
      tuberculosis, and thoracal bone fracture while investigating a cervical
      lymphadenopathy. Tuberculosis: a hidden enemy?

PMID- 20672505
TI  - Phenytoin induced status epilepticus.

PMID- 20672506
TI  - Knowledge and attitudes of Iranian patients with regard to lumber puncture.

PMID- 20672507
TI  - Neurosciences quiz. Eyelid fluttering artifact.

PMID- 20672508
TI  - Obstetric brachial plexus injury.

PMID- 20672509
TI  - Malaria progress report shows that development aid for health is working.

PMID- 20672510
TI  - Only 5.4% of world's population covered by comprehensive smoke-free laws.

PMID- 20672511
TI  - [Deep brain stimulation--the newest physical method of treatment of depression].
AB  - The deep brain stimulation DBS is the newest physical method of the treatment of
      depressive disorders. When applying of this technique in neurological illnesses
      (e.g., Parkinson's disease), mood changes were observed. In 2005, Helen Mayberg
      et al. used DBS in the therapy of the depression for the first time. Stimulating
      electrodes were placed in Brodmann areas 25. In the period of some past years,
      only about 30-40 patients with refractory depression have undergone DBS
      treatment. Numerous problems connected with applying DBS in patients with
      psychiatric disorders are described in the paper.

PMID- 20672512
TI  - [Differences in the course of depressive disorders among women and men measured
      by MMPI-2].
AB  - AIM: The aim of the study is to assess the differences between clinical scales of
      MMPI-2 among women and men suffering from depressive disorders. METHOD: 36
      patients were examined (aged 23-62 years, average age = 51.27, SD = 8.84): 19
      women (52.77%, aged 23-59, average age = 51.16, SD = 4.74) and 17 men (47.23%,
      aged: 23-61, average age = 51.41, SD = 12.07). All patients were hospitalised in
      the Clinic of Adult Psychiatry Medical University of Lodz. The Minnesota
      Multiphasic Personality Inventory (MMPI-2, adapted by T. Kucharski) and Hamilton
      Depression Rating Scale (HDRS, consisting of 21-items) were used. MMPI-2 is used
      in psychological diagnostic and HDRS is used to assess the intensity of
      depressive disorders. RESULTS: Relevant statistical differences between women and
      men in the several clinical scales of MMPI-2 were observed. There were no
      relevant statistical differences between the examined groups in the HDRS.
      CONCLUSIONS: (1). The characteristic symptoms of depressive disorders for women
      are: the excessive concentration on physical health, numerous complaints about
      physical disabilities, lack of energy, insomnia, diminishing of attention
      concentration and low self-esteem, diffidence and pessimism (2). Examined men
      achieved statistically lower results than women in the following scales:
      hypochondria, hysteria and D1, D3, D4 subscales of the depression scale. (3).
      MMPI-2 is one of the psychological methods which allow for a specific diagnosis
      of depressive disorders symptoms among women and men.

PMID- 20672513
TI  - [Psychological femininity and masculinity, self-appeal, attachment styles, coping
      styles and strategies of self-presentation among women with suicide attempts].
AB  - AIM: The aim of this study was to diagnose particular personality characteristics
      of women with suicide attempts: psychological femininity and masculinity, self
      appeal, attachment styles, self-presentation strategies and coping styles.
      METHOD: A group of 35 adult women who attempted suicide and the control group (35
      women) were submitted to a research. The following measures were used: Inventory
      of Gender Identity (IPP), Strategies of Self-presentation Questionnaire (KSA),
      Attachment Style Test, Sense of Self-Appeal Scale (SPWA), Coping Inventory of
      Stressful Situations (CISS). RESULTS: Female suicide-attempters had a lower index
      of psychological masculinity and a lower sense of self-appeal than women in the
      control group. They were characterised by an avoidant attachment style, used a
      strategy of self-depreciation in self-presentation and an emotion-oriented style
      of coping. The predictors of risk of suicide behaviours that mainly showed:
      avoidant-attachment style and strategy of self-depreciation in self-presentation.
      CONCLUSIONS: Parasuicides were characterised by lower self-esteem and weak
      interpersonal skills, which reduced their ways of coping in difficult situations.

PMID- 20672514
TI  - [Factorial structure of the general health questionnaire (GHQ-30)].
AB  - The General Health Questionnaire (GHQ) was designed by Goldberg in the 1970's as
      a screening instrument to provide information on the mental wellbeing. Although
      it is widely used as a unidimensional instrument, factor analyses tend to suggest
      that it contains more than one dimension. AIM: The purpose of this paper is to
      review the factor-analytic research that has been carried out with regard to the
      30-item General Health Questionnaire (GHQ-30) and to present the results of the
      analysis of our research. MATERIAL AND METHODS: A total of 623 patients suffering
      from neurotic disorders and somatic illnesses were included into the study, 130
      men and 493 women at the age ranged from 17 to 85 years old. A total score was
      calculated with Likert's method. The principal factor analysis with orthogonal
      varimax normalised rotation was used. Results. The GHQ-30 was found to have high
      internal consistency as a scale and high item-total correlations for most of the
      items. The factorial analysis showed that three factors labelled as the followed
      can be abstracted from the scale: depression and anxiety, interpersonal
      relations, general functioning. These factors jointly account for 58% of the
      variance. CONCLUSIONS: Results showed both multifactorial (at the level of a
      lower order) and unifactorial (at the level of an upper order) structure of the
      GHQ-30.

PMID- 20672515
TI  - [Neuropsychological examination among patients suffering from transient global
      amnesia].
AB  - Transient global amnesia (TGA) is a temporary disease with an unexplained
      aetiology. The clinical picture of TGA is characterised by retrograde amnesia
      (spanning from several days to several years), anterograde amnesia (from few to
      several hours, most often from 4 to 8), significant disorientation with respect
      to time (about 50% of the patients) and place (above 90% patients), preserved
      auto-orientation and preserved ability to recognise other people. The onset of
      transient global amnesia is sudden and unpredictable. Memory impairments in TGA
      are unspecific and they are not limited to one single sense or to one given type
      of material. In TGA there is a lack of comorbid neurological symptoms. Among 10
      20% patients after one TGA episode there is a possibility of a next one. Among
      the risk factors of transient global amnesia we can distinguish biological and
      psychological variables. The aim of the study is to present symptoms and
      aetiology of TGA and to show several neuropsychological methods which can be used
      in differential diagnosis.

PMID- 20672516
TI  - [Postraumatic kluver-Bucy syndrome--description and comparison of two clinical
      cases].
AB  - AIM: Kluver-Bucy syndrome was described in the fifties of the 20th century as a
      group of neuropsychological symptoms, such as visual agnosia, "oral" tendency,
      hypermetamorphosis, changes in behaviour, hyper-sexuality (homo-, hetero-,
      autosexuality) and changes in dietary habits (anorexia, bulimia) that may develop
      in humans after bilateral damage or dysfunction of the medial temporal lobes. The
      cause of Kluver-Bucy syndrome may be an injury, central nervous system infection,
      especially herpetic, Pick disease, temporal epilepsy and paraneoplastic
      encephalopathy. The condition is very rare in children; its occurrence in
      childhood was described in a few cases only. Symptom intensity and their
      manifestation depend on numerous diversified factors. METHODS: A comparative
      presentation of two clinical cases of Kluver-Bucy syndrome following severe head
      injuries accompanied by description of computed tomography scans. RESULTS: The
      diagnosis of the syndrome does not require the presence of all the axial
      symptoms. Both patients were treated with carbamazepine. Regression of
      neuropsychological symptoms took a different course in each child, despite their
      similar brain damage. CONCLUSIONS: Fully symptomatic Kluver-Bucy syndrome is very
      rare. The psychological status of patients with this disorder depends not only on
      the extent of the lesion, but also on pre-injury emotional and intellectual
      development and post-injury social stimulation.

PMID- 20672517
TI  - [The prospective assessment of the influence of duration of untreated psychosis
      (DUP) on the course of schizophrenia].
AB  - AIM: This study is a part of a prospective schizophrenia research project run in
      Krak6w. The general objective of the project is a long-time observation of people
      with schizophrenia, starting from the first episode through the years of living
      with the illness, the assessment of treatment results and predictors. The goal of
      this study was to investigate whether the level of DUP before the first admission
      may have a prognostic value in regard to the further course of the illness.
      METHOD: Four indicators of treatment results were observed: the number of
      relapses, the overall time of inpatient hospitalisations, the number of inpatient
      hospitalisations and the severity of psychopathological symptoms assessed in 3, 7
      and 12 years since the first hospitalisation. DUP was estimated during a clinical
      interview with a patient and his/her family at the index admission. The severity
      of symptoms was assessed with BPRS-SA, the UCLA version. RESULTS: The increase of
      the number of relapses in follow-up assessments was more prominent in the group
      with longer DUP (p < 0.001). The decrease of the results of BPRS (symptom
      improvement) was more prominent in patients with short DUP. They had
      significantly lower results compared to patients with long DUP at each assessment
      except the index hospitalisation (p equaled respectively: 0.449; 0.002; 0.012;
      0.034 and 0.014). The decrease of positive symptoms was larger in patients with
      short DUP - significant in all except the 7-year follow-up (p equaled
      respectively: 0.230; < 0.001, 0.011; 0.214; <0.001). CONCLUSIONS: (1) A
      relationship was found between the duration of untreated psychosis and the
      dynamics of general and positive symptoms and the number of relapses. (2) There
      was no significant relationship between the duration of untreated psychosis and
      the dynamics of negative symptoms, whereas the relationship between the time and
      number of re-hospitalisations was on the brink of statistical significance. (3) A
      replication of some and the lack of confirmation of other long-time results
      observed by other researchers prompts us to conclude that there still is a need
      for further studies concerning the duration of untreated psychosis

PMID- 20672518
TI  - [Could we use a serum level of glycine as a prognostic factor of its efficacy in
      schizophrenic patients?].
AB  - Glutamatergic system--the main excitatory brain system is involved in the
      pathophysiology of schizophrenia. The ionotropic glutamatergic NMDAreceptor
      participates in mechanisms of controlling neurotransmitter systems such as the
      dopaminergic, noradrenergic, serotoninergic ones and plays an important role in
      cognitive functioning. Glycine is a natural coagonist of the NMDA receptor and
      according to the hypoNMDA hypothesis treatment with its high doses (max. 60g
      orally per day) can improve symptomatology of schizophrenia, e.g., negative
      symptoms and cognitive functions. AIM: If there is a correlation between plasma
      levels (before and after using glycine) and severity of symptoms (at the first
      and last assessment), then low baseline plasma concentrations could be an
      indication for choosing glycine in treatment, moreover a useful prognosing tool
      and finally a support of glutamatergic hypothesis of schizophrenia. METHODS: 28
      patients with a diagnosis of schizophrenia according to ICD-10 diagnostic
      criteria (Table 1) in stable clinical condition and antipsychotic medication
      (typical and atypical agents) for min. 3 months, had completed a 6 week,
      prospective and open label study (32 patients enrolled). Between 2 visits
      patients received glycine in high oral doses (0.8 g/kg/day). Before and
      afterwards the glycine treatment, psychiatric and cognitive function examination
      was performed based on PANSS, Trail making test (TMT), Stroop test and Wisconsin
      card sorting test (WCST). In parallel glycine plasma levels were assessed.
      RESULTS: There was a significant reduction in positive, negative, general
      psychopathology and total PANSS score during the study (Table 2). Also cognitive
      parameters significantly improved during 6 weeks of glycine use. Serum levels of
      glycine were markedly higher at the end of our project, but only improvement in
      part 2 of TMT correlates with changes in aminoacid serum concentrations (p =
      0.02). CONCLUSIONS: Our results suggest that augmentation of antipsychotic
      treatment (typical and atypical neuroleptics) with glycine can have a positive
      influence on schizophrenic symptoms there in cognitive dysfunction, but glycine
      plasma levels were not a useful predictor of recovery in our patients.
      Correlation between improvement in performance of TMT and serum level increase
      suggests that glycine and NMDA receptor can be involved in psychopathology of
      schizophrenia and cognitive functioning, e.g., working memory

PMID- 20672519
TI  - [Family based association study of DRD1, DRD2, DRD3, DRD4, DAT, COMT gene
      polymorphism in schizophrenia].
AB  - AIM: The aim of the study was to estimate of the transmission of six candidate
      genes alleles (according to the dopaminergic hypothesis of schizophrenia) by
      parents to their children with schizophrenia. The genes under investigation were
      the following: DRD1 (polymorphism -48A/G), DRD2 (polymorphism -141C ins/del),
      DRD3 (polymorphism Ser9Gly), DRD4 (polymorphism -521C/T), DAT (polymorphism VNTR
      w 3'-UTR), COMT (polymorphism Val108(158)Met). Method. There were 116 families in
      the group under investigation (the ill person and his/her both parents). The
      patients and their parents were examined using SCID (Structured Clinical
      Interview for DSM-IV Axis I Disorders). No mental disturbances were found with
      all the patients' parents. The DNA was extracted from the peripheral blood
      leukocytes by the salting out method. Polymorphisms were studied by the PCR
      method (PCR-RFLP method for: DRDI, DRD2, DRD3, DRD4, COMT and PCR-VNTR method
      for: DAT). The statistical analysis of the frequency of transmission of alleles
      was carried out by the TDT (Transmission Disequilibrium Test) method. To analyse
      the transmission disequilibrium of alleles under examination, the Haploview v.
      3.2. programme was used. RESULTS: According to the results obtained, no
      connection between analysed polymorphism of genes: DRD2 (-141C ins/del), DRD3
      (Ser9Gly), DRD4 (-521C/T), DAT (VNTR), COMT (Val108(158)Met) and schizophrenia
      was stated. In the case of polymorphism -48A/G of gene DRD1, a trend was observed
      towards a more frequent transmission of allele A of gene DRD1 by parents to their
      children with schizophrenia (p = 0.091). CONCLUSIONS: This trend should be
      interpreted very carefully. There is also the possibility that other variant of
      gene in linkage disequilibrium with -48A/G polymorphism was responsible for the
      trend observed in this study.

PMID- 20672520
TI  - [The influence of atypical antipsychotics on brain functioning in schizophrenia.
      A proton magnetic resonance study].
AB  - INTRODUCTION: The influence of antipsychotic medication on brain alterations in
      proton magnetic resonance spectroscopy (1H MRS) in schizophrenia can be the
      explanation of many discrepancies observed in the previous papers. AIM: The aim
      of this study was the evaluation of antipsychotic medication effect on the
      metabolite levels in the brain of schizophrenic patients based on 1H MRS
      examination. METHODS: The group of 32 patients with a diagnosis of schizophrenia
      according to DSM-IV and 26 healthy controls were included into the study. The
      patients were examined twice--once after the period of at least 7 days without
      neuroleptics (baseline) and for the second time at least 4 weeks after stable
      doses ofneuroleptics (follow-up). 21 patients were receiving risperidone and 11-
      olanzapine. Proton resonance spectroscopy was performed on a 1.5 MR scanner. Each
      volume element (voxel) was localised in the left frontal lobe, in the left
      temporal lobe and in the left thalamus. Metabolite ratios: N-acetylaspartate
      (NAA) to creatine (Cr) and unsupressed water signal were analysed. Results. We
      found the significant increase of the NAA/Cr level in the thalamus in the group
      of patients treated with risperidone, we didn't observe similar changes in the
      olanzapine group. CONCLUSIONS: Our results confirm that the neuroleptic drugs,
      especially atypicals, modify brain metabolism measured by 1H MRS. The pattern of
      the changes suggest a possible neuroprotective influence of the antipsychototic
      treatment in schizophrenic patients. The small group of the olanzapine treated
      patients doses not allow to make any conclusions regarding this type of
      medication.

PMID- 20672521
TI  - [Perazine in the treatment of psychotic disorders--research review].
AB  - The author reviewed the relatively poor literature on the topic and its key
      clinical trial reports on perazine, a classical antipsychotic most frequently
      prescribed in Poland for psychoses, especially for schizophrenia. Based mainly on
      the Leucht and Hartung's metaanalysis as well as on other authors' trials with
      broader context of typical and atypical neuroleptics comparisons, it could be
      concluded that the perazine bearing balanced profile of psychotropic action
      (antipsychotic, anti-autistic and sedative) has also some atypical features which
      explain its broad applications in clinical practice. Not without a meaning are
      also a few dozen-fold lower costs of treatment, which are even more meaningful
      when costs of necessary laboratory tests required for monitoring atypical
      antipsychotics use are taken into consideration.

PMID- 20672523
TI  - Financed by the feds, states get tougher on rates.

PMID- 20672522
TI  - [Depression and pain: Polish epidemiologic study].
AB  - Depression is one of the most severe health issues of the modern medicine. One of
      the most troublesome symptoms of depression is pain. On the other hand, patients
      suffering from chronic pain problems are also often subjects of mood or anxiety
      disorders. There are still very little studies in the field of co-occurrence of
      these two symptoms and therefore there are no universal standards to deal with
      such cases. AIM: The aim of this study was to evaluate the relationship between
      symptoms of depression and pain. METHOD: The study consisted of 3726 female and
      2116 male participants, all patients of Mental Health and Neurological clinics.
      The mean age of the patients was 47 years. A structured questionnaire was used
      including data about demographics, Depression, Anxiety, and Pain Severity Scales.
      RESULTS: The data analysis revealed statistically significant relationship
      between severity of pain and depression, anxiety as well as suicidal thoughts.
      The study also revealed a high correlation between severity of mood disorders and
      the severity of pain. CONCLUSIONS: The patients with a long history of pain
      disorders have also an increase of depression and anxiety symptoms, and suicidal
      thoughts. Patients with more severe depression and anxiety symptoms have also an
      increase of pain problems. There is significant relationship between depression
      and pain symptoms, as well as between pain and suicidal thoughts.

PMID- 20672524
TI  - Concierge care at a discounted price.

PMID- 20672525
TI  - Will the employer-based system collapse?

PMID- 20672526
TI  - Specialists putting mark on strained primary care.

PMID- 20672527
TI  - Employers want more cooperation from plans. Interviewed by John Marcille.

PMID- 20672528
TI  - Vaccination is 1 oz. of prevention still worth 1 lb. of cure?

PMID- 20672529
TI  - Health care fraud resistant to reform.

PMID- 20672530
TI  - Comparison of amlodipine/valsartan fixed-dose combination therapy and
      conventional therapy.
AB  - PURPOSE: Single-pill-combination (SPC) antihypertensive drug products have been
      shown to improve compliance but are associated with higher acquisition costs.
      This study compared the clinical and economic outcomes associated with the use of
      an SPC of amlodipine/valsartan (trade name Exforge) with the outcomes from
      conventional combination therapy in patients failing to respond to initial
      monotherapy with either a dihydropyridine calcium channel blocker (DHP-CCB) or an
      angiotensin receptor blocker (ARB). DESIGN: We conducted a retrospective cohort
      study of hypertensive patients failing to respond to monotherapy with either a
      DHP-CCB or an ARB who were switched to an SPC of amlodipine/valsartan (SPC group)
      or to treatment that could not include any SPC (control group). The groups were
      matched for age, gender, race, baseline blood pressure (BP), and comorbidities.
      The primary outcomes of the study included the proportion of patients achieving
      BP targets, the absolute change in BP from baseline, the proportion of patients
      discontinuing drug therapy because of side effects, the proportion of patients
      non-compliant with drug therapy, and health care resource utilization and costs.
      PRINCIPAL FINDINGS: Fifty-eight SPC patients achieved BP targets compared with 47
      control patients (P = 0.119). The absolute reduction in BP was significantly
      greater in the SPC group (-22.8 +/- 6.9/-19.3 +/- 5.2 mmHg) than in the control
      group (-20.6 +/- 6.4/-17.8 +/- 5.6 mmHg) (P < 0.03). Significantly fewer patients
      discontinued anti-hypertensive therapy because of side effects and noncompliance
      in the SPC group compared with the control group (both P = 0.042). SPC patients
      accrued fewer clinic visits, laboratory tests, and electrocardiograms but had
      higher drug acquisition costs. Median medical therapy costs were significantly
      lower in the SPC group at the end of the 6-month follow-up, primarily because of
      lower costs for clinic visits. CONCLUSION: The use of the SPC of
      amlodipine/valsartan was associated with greater absolute BP reductions and fewer
      antihypertensive drug discontinuations because of side effects and noncompliance
      compared with the use of the individual drugs. Although the acquisition cost of
      the SPC was greater than that of the individual drugs, SPC combination therapy
      resulted in fewer clinic visits, laboratory tests, and electrocardiograms. As a
      result, the total cost of SPC therapy was significantly less than that associated
      with the use of the individual drug components.

PMID- 20672531
TI  - Closed formulary keeps student-run clinic afloat.

PMID- 20672532
TI  - Prosthetic hand provides nearly normal function.

PMID- 20672533
TI  - Medical home pilot offers docs leeway.

PMID- 20672534
TI  - For heart drugs, greater generic penetration.

PMID- 20672535
TI  - Nursing informatics: why nurse leaders need to stay informed.

PMID- 20672536
TI  - Practicum projects of value: a successful strategic partnership between nurse
      executives and master's level academia.
AB  - The opportunity exists for academia and the nursing executive community to
      collaboratively create cultures of excellence. One university formed
      relationships of collaborative synergy with nurse executives to provide practicum
      experiences of value for both the graduate nursing administration students and
      the health care facilities. The strategic preceptor partnerships offer graduate
      students the invaluable opportunity to experience the in-depth, real world
      perspective of nursing administration resulting in the enrichment of their
      academic scholarship. A final practicum work project is designed collaboratively
      with the preceptor and completed by the end of the second practicum semester. The
      resulting practicum project is an example of a mutually rewarding experience for
      the graduate nursing administration student and the preceptor. The collaborative
      synergistic model is a win-win situation for the university and the health care
      facility.

PMID- 20672537
TI  - Stress among charge nurses: tool development and stress measurement.
AB  - The aim of this study was to develop and implement a tool for measuring the role
      stress of charge nurses. Tools are lacking regarding measurement of nursing role
      stressors, particularly for charge nurses. Based on focus groups and in-depth
      interviews with charge nurses within a large tertiary hospital, a charge nurse
      stress questionnaire was developed which measures six factors of stress:
      authority-responsibility conflict, patient-nurse interaction, deficient
      resources, managerial decision making, role conflict, and overload. The prominent
      stressors on charge nurses were specific to the role. Mean levels of stress were
      significantly higher for nurses who attended post-graduate clinical courses than
      for those who did not. The mean level of stress was higher for department nurse
      managers than for nurses without a managerial position. This tool was designed to
      measure charge nurse stress demonstrates reliability, and highlights the specific
      stressors demanded by the role. Preparation and ongoing support for fulfilling
      this position are recommended.

PMID- 20672539
TI  - Creating a personalized professional practice framework for nursing.
AB  - Any organization on the journey to nursing excellence might initiate its search
      for a professional practice framework by exploring the many nursing-specific
      theories, frameworks, and conceptual models that are readily available in the
      literature. Although adopting an "off the shelf" professional practice framework
      for nursing may sound easier for a nursing organization than creating its own
      framework, achieving a good fit into an existing culture is more difficult when
      adopting rather than creating a practice framework. ven though creating a
      customized framework requires a considerable amount of upfront time, dedication,
      and a willingness to make some mistakes along the way, in the end a customized
      framework ensures cultural alignment. SThis framework describes the foundational
      structures and guiding principles, the key processes that influence how work is
      conducted, and the outcomes desired as the result of the work. Identifying
      evaluative methods for determining progress on identified strategic intents was
      crucial in bridging the gap between theory and outcomes. This model continues to
      provide flexibility and adaptability to meet needs in a constantly changing
      health care environment and difficult economic times.

PMID- 20672538
TI  - Cost effectiveness analysis of anesthesia providers.
AB  - Anesthesiologists and certified registered nurse anesthetists provide high
      quality, efficacious anesthesia care to the U.S. population. This research and
      analyses indicate that CRNAs are less costly to train than anesthesiologists and
      have the potential for providing anesthesia care efficiently. Anesthesiologists
      and CRNAs can perform the same set of anesthesia services, including relatively
      rare and difficult procedures such as open heart surgeries and organ
      transplantations, pediatric procedures, and others. CRNAs are generally salaried,
      their compensation lags behind anesthesiologists, and they generally receive no
      overtime pay. As the demand for health care continues to grow, increasing the
      number of CRNAs, and permitting them to practice in the most efficient delivery
      models, will be a key to containing costs while maintaining quality care.

PMID- 20672540
TI  - The characteristics of registered nurses whose licenses expire: why they leave
      nursing and implications for retention and re-entry.
AB  - Little is known about RNs who drop their licenses and their potential re-entry
      into the nursing workforce. The results of this study provide insight into
      reasons nurses leave their careers and the barriers to re-entry, all important
      indicators of the current professional climate for nursing. While representing
      only one state, these findings suggest that RNs who allow their licenses to
      expire do so because they have reached retirement age or, among those who do not
      cite age as a factor, because many are unable or unwilling to work in the field.
      Inactive nurses who might otherwise appear to be likely candidates for re-entry
      into the profession may not be easily encouraged to practice nursing again
      without significant changes in their personal circumstances or the health care
      work environment. Effective ways to address current and pending RN workforce
      shortages include expanding RN education capacity to produce more RNs who can
      contribute to the workforce across the coming decades, and promote work
      environments in which RNs want to, and are able to, practice across a long
      nursing career.

PMID- 20672541
TI  - What nurses need to know about health care reform.

PMID- 20672542
TI  - Candidate marketing takes the guessing game out of choosing employers.
AB  - Candidate marketing builds a foundation for relationships between employers and
      potential employees. Additionally, candidate marketing differentiates
      organizations in the marketplace. Organizations using candidate marketing to
      communicate the employer brand can expect a higher quality of candidates, and new
      employees are better prepared for the work environment and culture. Today,
      organizations can use a variety of integrated tools and techniques to communicate
      and build relationships with candidates. Candidate marketing demonstrates an
      organization's willingness towards transparency, and ability to invite open
      conversations between candidates and members of the organizations.

PMID- 20672543
TI  - Is U.S. health care evolving toward a single-payer system? An interview with
      health care economist Paul Feldstein, PhD. Interview by Peter I Buerhaus.

PMID- 20672544
TI  - The board's role in organizational finance.
AB  - Health care reform will result in significant changes in reimbursement with much
      greater emphasis put on primary care, home care, and other types of non-acute
      care. The changes in reimbursement will necessitate significant changes in
      organizational structure and operations. It is essential board members keep
      current in their knowledge of health care finance so they can execute their
      responsibilities for the financial health of the organization. The board must
      ensure that the budget is aligned with the organization's financial objectives
      and monitor the financial performance. It is essential the chief nursing officer
      (CNO) contributes to the board's understanding of the financial health of the
      organization. The board of trustees will more effectively execute their financial
      responsibilities with the input of nurse trustees and the CNO.

PMID- 20672545
TI  - Nursing informatics: the intersection of nursing, computer, and information
      sciences.
AB  - Nursing informatics (NI) is a well-established specialty within nursing.
      Background on the birth and evolution of NI, and the NI scope of practice and
      certification are explored. NI has played a vital role in influencing health care
      information system features and functions. Today, nursing informatics has evolved
      to be an integral part of health care delivery and a differentiating factor in
      the selection, implementation, and evaluation of health IT that supports safe,
      high-quality, patient-centric care.

PMID- 20672546
TI  - Are your nurse managers ready for health care reform? Consider the 8 'Es'.
AB  - The most significant investment a nursing executive can make in an organization
      and to the delivery of quality patient care is the development of current and
      future front-line nurse managers. We are on the brink of massive changes in
      access and the delivery of health care. The front-line manager is in a critical
      position to make it all work and deliver what the public wants: better access,
      improved quality, and less cost. If front-line nurse managers are key
      stakeholders and will undoubtedly play a major role in health care reform, are
      they ready? Nurse leaders must evaluate, educate, embrace, enable, empower,
      espouse, engage, and excite frontline nurse managers in order to expand health
      care services efficiently and effectively.

PMID- 20672547
TI  - Solving leadership problems by going to the zoo: the pull of diverse experiences.
AB  - Being confronted with a diversity of thinking can break up the old models in our
      head and open new pathways to innovation. In health care, it is extremely
      important to be exposed to very different situations that can potentially create
      very different answers for us; hence the trip to the zoo, to a factory known for
      quality outcomes, or other venues that will open new vistas in our mind. Anytime
      we try to do something that worked in the last 5 years, we are flirting with
      disaster. Health care is constantly changing and if we attempt to cover the
      present with the templates of the past, we will fail. Immersing people in
      situations where they can share openly with very diverse people and ideas will
      create the culture consistent with behaviors that eagerly engage in seeking
      diverse answers to the issues of the future.

PMID- 20672548
TI  - What's the real cause of rising health care costs?

PMID- 20672550
TI  - The worst doctor in the worst clinic.

PMID- 20672549
TI  - Portraits in the boardroom.

PMID- 20672551
TI  - Examining the effect of gardening on vegetable consumption among youth in
      kindergarten through fifth grade.
AB  - INTRODUCTION: Funded by a grant from the makers of Hidden Valley Salad Dressings
      the objective of this study was to determine if the introduction of a school-wide
      gardening program would affect overall vegetable consumption among elementary
      school youth. The study's setting was Elmore Elementary, Green Bay, Wisconsin, 1
      of 27 elementary schools in the Green Bay Area Public School District. PROGRAM
      DESCRIPTION: The school's salad bar was used to measure changes in vegetable
      consumption during school lunch. School food service staff recorded the weight of
      vegetables selected from the salad bar. The daily total weight of vegetables
      selected from the salad bar was divided by the number of students purchasing
      lunch that day. The resulting factor (average grams per child) was charted to
      monitor changes in consumption. After approximately 10 weeks of data collection,
      a gardening program was introduced. Food service staff continued to record
      weights, allowing for a quantitative analysis of the group's consumption prior
      to, during, and postintervention. RESULTS: Selection of vegetables from the salad
      bar decreased (r = -.403) during the first 2 1/2 months of the study. During the
      intervention period, selection increased (r = .3940) and continued to show a
      slight rise postintervention (r = .2037). CONCLUSION: The negative trend in daily
      salad bar selection before intervention was reversed, and a steady increase per
      day was seen during the intervention period. This suggests that intervention
      helped increase consumption rates per student. Consumption continued to increase
      postintervention, although at a lesser rate than during intervention. The average
      daily value also showed a slight increase between intervention and
      postintervention. This suggests that gardening intervention lessons and
      activities were retained by the students after the lessons and activities were
      completed.

PMID- 20672552
TI  - Occupational respiratory health: a survey of Wisconsin workers who wear
      respirators.
AB  - CONTEXT: Little is known about Wisconsin workers who wear respirators and the
      prevalence of work-related asthma (WRA) in that population. To understand this
      problem, we questioned workers who wear respirators. OBJECTIVES: The primary
      objective was to learn more about the health experiences of workers who wear
      respirators. A secondary objective was to evaluate the utility of the survey in
      WRA surveillance. DESIGN: A survey was mailed to an opportunistic sample of
      workers who received medical evaluation for respirator fit testing. PARTICIPANTS:
      Surveys were sent to 1356 workers medically evaluated to wear a respirator; 192
      surveys were completed and returned. RESULTS: The majority of respondents were
      men who have been medically evaluated for respirator wear an average of 3 times
      during their career. Every time, most respirator medical evaluations used 3
      evaluation tools: questionnaire, physical exam and breathing test. Thirty-two
      percent of survey respondents had some asthma symptoms while at work in the last
      30 days, and half reported discussing these symptoms with a physician. Lifetime
      prevalence of asthma as determined by this survey was 18%. Lifetime prevalence
      for WRA amongthis population was 3% (18% among those with asthma). CONCLUSIONS:
      This survey was an efficient and effective way to learn more about workers'
      respirator experiences and to determine the prevalence of asthma in this
      population. Few differences existed between those with asthma and those without.
      However, some differences were noted between those with asthma and those with
      WRA. Data also suggest that the respirator medical evaluation process provides an
      opportunity for health practitioners to discuss asthma and asthma prevention with
      workers.

PMID- 20672553
TI  - The effect of physician workload on an educational intervention to increase
      vitamin D screening.
AB  - RATIONALE, AIMS AND OBJECTIVE: Changes in physician behavior are difficult to
      accomplish. We hypothesized measuring physicians' vitamin D levels would increase
      measurement of their patients' levels. METHODS: We recruited faculty via e-mail.
      We measured physicians' serum 25(OH)D levels and asked them to complete a
      questionnaire created to assess the risk of vitamin D deficiency. Physicians
      received their vitamin D test results by mail. We monitored physicians' vitamin D
      testing rate per 100 patient visits in the 12 weeks before and after receipt of
      their own vitamin D test result. RESULTS: Twenty-eight (22%) of 126 primary care
      physicians participated in the study; all were Caucasian and 17 (61%) were women.
      Gender, practic type, and year of graduation from medical school were similar in
      participants and non-participants. Over half of participants took a multivitamin
      and a third took a vitamin D supplement. Although 6 (21%) reported a recent
      fracture, only 1 physician carried a diagnosis of osteopenia or osteoporosis. At
      baseline, geriatricians ordered 14 vitamin D tests per 100 patient visits, while
      internists and family practitioners ordered substantially fewer tests (2 and <1
      tests per 100 visits, respectively). After study participation, vitamin D testing
      rates increased significantly among family practitioners (rate ratio 3.27, 95% CI
      1.29-8.33) and internists (rate ratio 3.19, 95% CI 1.12-9.07). Physicians with
      heavier clinic workloads were half as likely (rate ratio 0.50, 95% CI 0.32-0.76)
      as those with lighter clinic workloads to increase vitamin D testing rates.
      Surprisingly, physicians with hypovitaminosis D demonstrated no change in vitamin
      D testing rates. CONCLUSIONS: Physicians with low vitamin D testing rates were
      receptive to a personal intervention involving measurement of their own vitamin D
      levels. High workload appeared to attenuate this effect. These novel but
      preliminary observations require confirmation in future studies.

PMID- 20672554
TI  - Medical student exposure to and attitudes about pharmaceutical companies.
AB  - PURPOSE: Medical students are at-risk to the influence of pharmaceutical company
      (Pharma) marketing. As interactions with the industry come under increasing
      scrutiny and regulation, previous studies on student-Pharma relations no longer
      may be accurate. This study assessed students' attitudes toward and interactions
      with Pharmas at the University of Wisconsin School of Medicine and Public Health
      (UWSMPH). METHOD: A modified questionnaire based on a previously administered
      national survey was completed by students in April and May 2009. The survey was
      analyzed to disclose the frequency of student-Pharma interactions, where
      interactions took place, and differences between preclinical and clinical
      students. RESULTS: The overall response rate was 53.6% (348/649). Most student
      Pharma interactions took place at locations remote from the main campus, with
      free lunches (70.2%), snacks (66.9%), and small, non-educational items (55.8%)
      representing the most common gifts. Many clinical students had discussed medical
      personnel-Pharma interactions with a physician or friend. Of those surveyed, 78%
      felt they had received limited instruction from the school on how to interact
      with Pharma representatives. Preclinical students expressed greater uncertainty
      about using Pharmas as educational resources and were more reluctant to accept
      Pharma gifts than clinical students. DISCUSSION: Student attitudes toward
      interactions with Pharmas reveal the need for further education and guidance
      particularly on the risks of using Pharmas as educational resources. Pharma
      exposures remote from the main campus account for a high proportion of all
      interactions, which further highlights the need to educate students on conflicts
      of interest during their preclinical training.

PMID- 20672555
TI  - Treatment of intractable hip pain after THA and GTB using peripheral nerve field
      stimulation: a case series.
AB  - OBJECTIVE: It has been estimated that 10%-35% of patients who undergo total hip
      arthroplasty (THA) have chronic postoperative pain, most often located at the
      greater trochanter. After greater trochanteric bursectomy (GTB), patients also
      may continue to experience chronic surgical site pain. Chronic pain has a
      neuropathic component, which often responds poorly to opioids. In an attempt to
      provide increased pain relief for patients with intractable chronic pain,
      unconventional agents and interventional management approaches have received
      considerable attention. Peripheral nerve field stimulation (PNFS) has been used
      with increased frequency as a minimally invasive and safe intervention for the
      management of intractable neuropathic postoperative pain. The objective of this
      retrospective study was to evaluate the efficacy of PNFS for treatment of chronic
      hip pain after THA and GTB. METHODS: Twelve patients with chronic post-operative
      pain after THA and GTB underwent an uneventful PNFS trial with percutaneous
      placement of 2 temporary 8-electrode leads (Medtronic Inc, Minneapolis, Minn)
      positioned in the subcutaneous tissue in the area of greatest pain, parallel to
      postoperative scar over the affected upper lateral thigh. RESULTS: After
      experiencing excellent pain relief over the next 2 days, the patients were
      implanted with permanent leads and rechargeable or non-rechargeable generator 2-4
      weeks later. They reported sustained pain relief at 12-month follow-up visits.
      CONCLUSION: PNFS provides an effective alternative treatment option for select
      patients with chronic postoperative pain after THA and GTB who have failed
      conservative treatment.

PMID- 20672556
TI  - HHV-6 infection in a case of an infant with fever, seizures, and shock.

PMID- 20672557
TI  - Seeding new ideas in adolescent eating habits.

PMID- 20672558
TI  - Research effects of CPR performed by bystanders and more.

PMID- 20672559
TI  - Local response to infectious diseases facilitated by resources and preparedness.

PMID- 20672560
TI  - Wisconsin makes significant changes to HIV consent and disclosure requirements.

PMID- 20672561
TI  - The surgical care improvement/heart failure project.

PMID- 20672562
TI  - President's inaugural address. Wisconsin Medical Society.

PMID- 20672563
TI  - Two honored with Physician Citizen of the Year Awards for compassionate, patient
      centered care.

PMID- 20672564
TI  - [PillCam capsule endoscopy for the diagnosis of colonic diseases].
AB  - PillCam Colon Capsule Endoscopy (PCCE) represents one of the newest diagnostic,
      endoscopic technology designed to explore the colon. It is a non-invasive,
      swallowing colonoscope that is able to explore the colon without requiring
      sedation, nor radiation. The colon capsule measures 31 mm x 11 mm. It has dual
      cameras that enable to take pictures from both ends at a frame rate of 4 frames
      per second. The goal of PCCE is to substitute the conventional colonoscopy in the
      diagnosis of colonic diseases and to discriminate patients who deserve a
      conventional colonoscopy. Although the preliminary results available in
      literature are encouraging, further studies are needed to confirm and increase
      the accuracy parameters and to select a more tolerable and effective regimen of
      preparation.

PMID- 20672565
TI  - [Ageing and cardiac function. Is there a role of physical exercise?].
AB  - Ageing of the human heart is characterized by morphological, functional and
      metabolic changes regardless the development of ischemic heart disease. Physical
      exercise is in general considered capable to counteract the onset of these
      changes; nevertheless short-term interventions and cross sectional studies in
      older individuals questioned the possibility that physical exercise may revert
      these alterations. Metabolic factors, development of overt cardiac diseases and
      probably the timing of the intervention with physical exercise during the life
      span of a single individual may explain the controversial results reported in the
      literature.

PMID- 20672566
TI  - [Continuing medical education for the quality of the profession].
AB  - Doctors are obliged by law, for the duration of their professional career, to
      keep up to date their skills and knowledge base, by following developments in
      medical science and improvements in health technologies. This is important to
      build a patient/doctor relationship based on trust, in agreement with the
      detailed laws regulating the medical profession. The experimental stage of the
      national program of continuing medical education (CME) has revealed some areas
      which need to be developed; with the objective of guarantying healthcare workers
      effective training to improve the health of the patients. CME should favour the
      capacity of health professionals to always critically incorporate new knowledge;
      refine methodological skills and combine them in their everyday professional
      work; allowe human and professional growth.

PMID- 20672567
TI  - [Continuing medical education and the Social Balance Sheet].
AB  - The social balance sheet is an instrument used to obtain a clear and transparent
      account, that helps to develop an analysis of the budget from the point of view
      of the stakeholders; this is not all that is required by law, but it takes into
      account the ability of the health institutions to obtain a collaboration with the
      neighboring environment and with the social issues that enter into the
      relationship. This could be a valuable tool also for educational purposes; it is
      an useful task to be performed by the health workers, and an opportunity to
      redefine the information needs through the analysis of the results achieved.

PMID- 20672568
TI  - [From the health plan to teaching and learning plan: pathways for the planning of
      CME in the Provincia Autonoma of Bolzano (Italy)].
AB  - Evidence based medicine (EBM) proposes a step by step pathway, that represents
      today an useful methodological reference to make clinical decisions. The authors
      propose that this methodological approach (define the problem; searche the best
      evidence; evaluation of the results in conjunction with the skills and experience
      that the health worker has already acquired; evaluation of the whole process),
      can be used to guide the questions in the use of CME. CME experience in the
      Provincia Autonoma of Bolzano (Italy) is shortly reported, emphasizing the
      involvement of the different stakeholders in planning and verification of
      teaching and learning.

PMID- 20672569
TI  - [Which tools should be used to identify learning objectives for the health
      service? The experience of the Emilia-Romagna Region (Italy)].
AB  - The main health education target of the Emilia-Romagna Region for the period 2008
      2010 is to develop pathways of continuous learning for healthcare workers and
      managers in hospitals. The pathways have the aim of governing the innovation
      process, improving services, developing new skills, spreading good managerial and
      professional working practices and integrate knowledge and cooperation between
      professions at institutional and service levels. This paper synthetically
      illustrates the role of the different regional institutions (primary care trusts
      and NHS trusts) in establishing the objectives and the preferable procedures for
      teaching. The main difficulties concern the effective planning of homogeneous
      teaching, as well as the ways to translating the needs of the health of the
      patients into educational projects.

PMID- 20672570
TI  - [Which tools should be used to identify educational objectives in the regional
      health service? The experience in Marche Region (Italy)].
AB  - Through a specific methological path, educational objectives of Regional interest
      have been identified with a punctual analysis of Health Planning documents. While
      organizing each educational acrivities, all SSR departments indicate the Regional
      educational objectives they are linked with, each connected to national
      educational objectives. Continuing Medical Education program in the Marche Region
      is strictly connected with the acts of health planning from 2006. Each SSR
      department report accompanying the balance sheets from 2006 to 2009 must contain
      a section specifically dedicated to ECM Program, indicating the annual budget for
      ECM Program. All training activities are systematically monitored through a
      single information tool, shared by all SSR Departments and linked to the SSR
      Health Operators registry office. Strenghts of the ECM Educational Program of the
      Marche Region can be summarized as follows: guidance of Educational Program
      linked in a structured way to the Health Planning goals; punctual indications of
      redaction modes for PFA and Educational Reports; analytical scanning of
      activities/costs of the whole Regional Health Service training system, allowing
      Executive monitorings and reports, i.e. data that General Management can (...
      should) use to redirect not only training but their Company management as well.

PMID- 20672571
TI  - [Which tools should be used to identify educational objectives? The experience of
      the Tuscany Region].
AB  - The tools used by the Tuscany Region to identify its training objectives show the
      Region's training network. Continuing education is planned, delivered, and
      evaluated by an "educational networking". This means that people involved in the
      educational process are not alone but are part of a network constituting a
      system, which is linked at three interconnected levels: Regional, sub-Regional
      (consortia of local health units linked together according to their geographical
      position), and "Area Aziendale". The three levels contribute to outline
      strategies, to bring into focus the information needs, to match them and to
      evaluate the effectiveness of the CME.

PMID- 20672572
TI  - [What evidence that continuing education is effective? Focus on residential
      training].
AB  - The paper assesses effectiveness of Continuing Medical Education (CME) on the
      basis of five points: the principles that rule adult learning, the main outcomes
      of CME, the evidence of effectiveness of CME, the features of an evidence-based
      residential course and the new Italian CME system in the clinical governance era.
      The author emphasizes the lack of proof of effectiveness in traditional
      residential teaching and illustrates the essential features of a workshop
      finalized to changing the behaviors of the participants: preliminary evaluation
      of the educational objectives; interaction with the teachers; small working
      groups; problem-based learning; learning by doing; reinforcement of teaching with
      other formative problems.

PMID- 20672573
TI  - [E-learning and the continuing professional development in medicine].
AB  - E-learning is widely used in continuing medical education but three main problems
      still face health decision makers: the substantial heterogeneity among the
      characteristics of the web-based educational projects; the concerns about the e
      learning effectiveness; the variety of outcomes used to evaluate the
      effectiveness. Systematic reviews suggest e-learning has effectiveness similar to
      traditional educational methods.The attention should now be given to how and when
      can we use e-learning to improve the health workers' performance and better
      healthcare.

PMID- 20672574
TI  - [Erythropoietin: pleiotropic actions].
AB  - The erythropoietin is produced by the kidney and other organs. EPO does not only
      affect erythroid cells, but also other blood cell lines, such as myeloid cells,
      lymphocytes and megakaryocytes. This hormone can also enhance phagocytes function
      of the polymorph nuclear cells and reduces the activation of macrophages, thus
      modulating the inflammatory process. Hematopoietic and endothelial cells probably
      have the same cellular origin, and the discovery of erythropoietin receptors also
      on mesangial and myocardial cells and smooth muscle fibro-cells has prompted the
      study of the pleiotropic actions of this hormone. Through its receptors, spread
      out over the body, it carries out many actions which range from the
      erythrogenesis after hypoxic stimuli to the tissue protection of the heart and
      the brain after ischemia. Erythropoietin also acts in the endothelial
      proliferation of new vessels involving the tumor genesis, but it opens new
      frontiers to the employment of rHuEPO in the Regenerative Medicine.

PMID- 20672576
TI  - [A hot cold man. Frostbite in summer? Polyneuropathy, vitamin B12 deficiency].

PMID- 20672577
TI  - [Public health insurance sees potential savings in physician reimbursement. Where
      is the fat that can be trimmed?].

PMID- 20672578
TI  - [Hypothyroidism and adrenal cortex insufficiency. Hormone replacement-
      individually controlled].

PMID- 20672579
TI  - [Climacteric in men. When is hormone replacement of value?].

PMID- 20672580
TI  - [Benefits and risks of postmenopausal hormone replacement therapy. Symptoms
      improved but not a better outcome?].

PMID- 20672581
TI  - [Clostridium difficile infections. Not just a hospital problem].

PMID- 20672582
TI  - [Naturopathy consultation. Fibromyalgia syndrome].

PMID- 20672583
TI  - [Many colleagues are overburdened. How is your mental health?].

PMID- 20672584
TI  - [Substance use and suicide in physicians].

PMID- 20672585
TI  - [Burnout--ways to prevention and therapy].

PMID- 20672586
TI  - [Hand eczema].

PMID- 20672587
TI  - [Pediatric emergencies, part 2].

PMID- 20672588
TI  - [Upper gastrointestinal bleeding].

PMID- 20672589
TI  - [Diabetic neuropathies and angiopathies. Compensating for thiamine deficiency].

PMID- 20672590
TI  - [Study on TPS434 infrared detector at low temperature and magnetic field].
AB  - The response of a commercial thermopile TPS434 to IR light as a function of
      temperature between 280 and 10 K, chopper frequency between 0.1 and 100 Hz, and
      magnetic field between 0 and 6T was measured in order to investigate its
      suitability for THz detection. The data show that the sensitivity of TPS434
      decreases with the decrease in temperature or the increase in chopper frequency.
      The relaxation time of TPS434 at low temperature is smaller than that at room
      temperature, which can improve the system response time. Thermopile's
      thermoelectromotive force increases linearly under low temperature with the
      magnetic field increasing, but the influence of the magnetic field can be
      deducted through the linear fitting to the measurement result. The possibility of
      using the device as a THz detector was analyzed by estimating the equivalent
      noise power (NEP) and the smallest detected power P(min).

PMID- 20672591
TI  - [Rotational and vibrational state distributions of CsH in the reactions of Cs(6
      2D5/2) with H2].
AB  - The nascent quantum state distributions of the CsH product resulting from the
      reaction Cs(6D5/2) with Hz were determined using a laser pump-probe technique in
      a five-arm crossed heat-pipe oven. Cs-H2 mixture was irradiated with pulses of
      885.4 nm radiation from a OPO laser, populating 6D5/2 state by two-photon
      absosption. Laser induced fluorescence was used to detect CsH molecules directly
      at the collision volume by scanning pulse tunable dye laser over X 1 sigma+ (v",
      J") --> A 1 sigma+ (v', J' = J" +/- 1) absorption line. The vibration bands (v" =
      0, v' = 6) and (v" = 1, v' = 9) were chosen. For the investigated reaction, the
      nascent CsH product molecules were found to populate the lowest two vibrational
      (v" = 0, 1) levels of the ground electronic state but could not be detected in
      any higher vibrational state. Rotational distributions of CsH products obtained
      for v" = 0 and 1 states appear to be monomodal , peaking in J = 6-8. The
      rotational population profile is roughly consistent with a statistical
      distribution at the system temperature. A plot of logarithm of relative
      population of states J divided by the degeneracy factor (2J + 1) against J (J +
      1) was yielded. The linearity of the plot establishes the Boltzmann form for
      rotational distributions of both the v" = 0 and 1. The rotational temperatures
      are (458 +/- 20) K and (447 +/- 18) K for v = 0 and 1, respectively. The nascent
      CsH rotational temperatures were found to be slightly below the cell temperature.
      The relative vibrational population was determined to be 0.527 and 0.473. The
      average vibrational and rotational energy release can be computed. The relative
      fractions (fv), (fR) and (fT) of average energy disposal were derived as 0.25,
      0.10 and 0.65 respectively, having a major translation energy release. All of the
      above results support the assumption that the Cs(6 2D5/2)-H2 reaction occurs
      primarily in a collinear geometry by a harpoon mechanism but not an insertion.

PMID- 20672592
TI  - [Research on high resolution spectrum measurements of methane at 1.65 microm].
AB  - The high resolution spectrum of methane was obtained around 1.65 microm using a
      tunable DFB diode laser with a long adjustable optical path white * cell (46.36-1
      158.90 m) at room temperature through the direct absorption technique. The
      typical line width of the DFB diode laser is about 10 MHz and the wavelength of
      DFB laser was calibrated by an optical wavemeter. A total of 259 new absorption
      lines were studied from 6 043.00 to 6 053.72 cm(-1) at five different pressures
      and optical lengths. All the data were fitted by Gaussian profile, the line
      intensities, positions and the percent of the statistical standard deviation
      (sigmaS/ S) % of the line intensities were obtained, and the absorption lines
      which are hard to be distinguished were analyzed in this paper. The weakest
      absorption line is 4.3 x 10(-27) cm(-1) x (mol x cm(-2))(-1), while the lines
      stronger than 3.0 x 10(-24) cm(-1) x (mol x cm(-2))(-1) were ignored for their
      saturated absorption due to the long absorption optical length(788-1 000 m).
      Meantime, the spectrum shows the abundance of methane weak lines and its
      extremely complex structure around 1.65 microm. All the lines cannot be found in
      HITRAN2004 database, and as to our knowledge, they were not reported before by
      other papers.

PMID- 20672593
TI  - [Spectroscopic investigation of the argon plasma discharge in quartz capillary at
      atmospheric pressure].
AB  - An arc plasma discharge with a long length of 20 cm was generated in a quartz
      capillary between two hollow needle electrodes in argon at atmospheric pressure
      with use of the sinusoidal power supply operating at 45 kHz, which was
      characterized by a very high electron density. The spectroscopic method of
      optical emission was employed to diagnose the characteristic parameters of the
      arc plasma discharge in the quartz capillary. The gas temperature was determined
      by simulating the OH A-X(0, 0) vibrational band around 300 nm and comparison with
      measured spectrum by means of optical emission spectroscopy. Furthermore, the
      electron density was measured by means of Stark broadening of the profile of
      Hbeta at 486.1 nm. The electron temperature was determined using a Boltzmann plot
      method. The experiment results show that in the argon arc plasma discharge
      generated in the quartz capillary at atmospheric pressure, the gas temperature of
      plasma is about (1 100 +/- 50)K, the electron density at the gas temperature of 1
      100 K is approximately 10(14) cm(-3), and the corresponding electron temperature
      is (14 515 +/- 500)K. This work has accumulated some significant experimental
      parameters for the treatment of inner surface of large length-to-radius-ratio
      insulated dielectric tube using plasma, and the results are of great importance
      to the applications of this type of atmospheric-pressure plasma discharge.

PMID- 20672594
TI  - [Preparation and spectral characterization of Lumogen coatings for UV-responsive
      CCD image sensors].
AB  - Traditional charge-coupled devices (usually front-illuminated CCDs) and
      complementary metal oxide semiconductor (CMOS) have lower response in ultraviolet
      region particularly. The reason is that polysilicon gate material absorbs the
      ultraviolet radiation highly, which leads to a barricade of the radiation
      penetrating the gate to the channel of CCD. To enhance the detective
      responsibility of CCD in the ultraviolet region, a feasible method is to coat the
      surface of CCD polysilicon gate with a thin film. The thin film should have the
      ability of converting the ultraviolet to visible in order to enable the UV
      radiation to "penetrate" the polysilicon gate. An organic coating to convert the
      UV radiation to visible has been developed in the present paper. Lumogen thin
      films were deposited on fused silica substrates by vacuum evaporation of an
      organic dye called Lumogen Yellow S0790. Analysis of organic functional groups
      was used to study the luminescence mechanism of Lumogen. The optical constants of
      coatings were calculated by spectroscopic ellipsometry. The results indicate that
      Lumogen exhibits photoluminescence continuously owing to four kinds of double
      bonds in each Lumogen molecule. The refractive index of Lumogen film was
      approximately 1.3, which indicates that this film could be considered an
      antireflection coating. Finally, the spectral properties of Lumogen coatings were
      characterized by transmission, absorption, photoluminescence emission, and
      excitation spectra. It is showed that these coatings were transmitted well in
      visible region (lambda > 470 nm), and emitted a yellowish green glow centered at
      approximately 523 nm together with a wide excitation spectrum field from 240 nm
      to 490 nm. The synthesis shows that Lumogen coatings match accurately with the
      detected spectrum of conventional silicon-based image sensors, which makes this
      kind of thin films an ultraviolet responsive coating for sensors.

PMID- 20672595
TI  - [Enhancing effect of sample additive on laser-induced plasma radiation].
AB  - In order to improve the radiation characteristic of laser-induced plasma, with
      the national standard soil taken as the target sample, a laser spectrum
      analytical system which composed of a high-energy neodymium glass laser, a
      multifunctional and compact integrated spectrometer, and a CCD detector was used
      to detect the influence of the NaCl sample additive on the laser plasma radiation
      intensity. The electron temperature and the electron density of the plasmas were
      also calculated from the lines intensity and stark broadening of emission
      spectral line respectively. The experimental results indicated that with the
      increase in the NaCl additive, the spectral intensity, signal-to-background
      ratio, the electron temperature, and the electron density all went up firstly and
      then down. When 15% NaCl was added, the radiation intensity of the plasma reached
      the maximum value, the spectral lines intensity of element Mn, K, Fe, and Ti
      increased by 39.2%, 42.5%, 53.9% and 33.8% compared to that without additive
      respectively, the spectral signal-to-background ratio increased by 64.4%, 84.39,
      44.55% and 58.2% respectively, while the electron temperature and the electron
      density of the plasmas were heightened by 0.17 times and 0.36 times respectively.

PMID- 20672596
TI  - [Influence of the amount of H2O on the emission spectra of Tb doped SiO2
      xerogels].
AB  - Tb-doped luminescent SiO2 xerogel was prepared by the sol-gel technique. FTIR was
      used to measure the microstructure of the luminescent materials. The luminescence
      properties were characterized by F-7000 UV-visible fluorescence
      spectrophotometer. The effects of the molar ratio of H2O on the fluorescence and
      phosphorescence intensity and phosphorescence lifetime of the sample were mainly
      investigated. The results showed that for the Tb3+ doped xerogels, the sample of
      1 : 4 : 4 annealed at 650 degrees C reaches the maximum intensity, the sample of
      1 : 4 : 5 annealed at 750 degrees C reaches the maximum, the sample of 1 : 4 : 6
      annealed at 850 degrees C is the strongest. With increasing the amount of water,
      the luminous intensity of the samples annealed at 750 degrees C was first
      weakened, then enhanced and finally weakened. It was shown that the luminous
      intensity of samples is related to the molar ratio of aqueous solutions and
      annealing temperature, whose influence on the luminous intensity formed a
      competitive mechanism. Phosphorescence was observed at the same time,
      illustrating the existence of defects in the matrix space, and that the influence
      of water on the intensity is the same as that of fluorescence. In addition, with
      the increase in the molar ratio of aqueous solutions, the amount of defect
      gradually changed and resulted in a change in the luminescence decay time.

PMID- 20672597
TI  - [Two-dimensional synchronous correlation spectroscopy for probing fluorescence
      energy transfer].
AB  - In the present paper, the authors developed a new approach by constructing two
      dimensional (2D) UV-Vis/fluorescence heterogeneous synchronous spectrum based on
      the orthogonal sample design scheme (OSD) developed in our previous works to
      characterize energy transfer among different lanthanide ions during the
      luminescence process. The authors use the EuCl3-NdCl3 system as an example. The
      preliminary experimental results on the 2D synchronous spectra of EuCl3-NdCl3
      mixture solutions have demonstrated that cross peaks can be observed among the UV
      Vis absorption bands from Nd3+ and fluorescence emission bands from Eu3+. The
      cross peaks in the 2D synchronous spectra of EuCl3-NdCl3 mixture solutions
      manifested the interaction between the fluorescence emission from Eu3+ and UV-Vis
      absorbance from Nd3+, and therefore gives out experimental evidences for the
      occurrence of energy transfer between Eu3+ and Nd3+ ions. The cross peaks are not
      from the interaction between the solvent, water, and the solute, Eu3+ or Nd3+
      ions. Mathematical analysis performed on 2D synchronous spectra using variable
      concentration as an external perturbation shows that the orthogonal sample design
      scheme is indispensable in removing the interfering cross peaks in 2D synchronous
      spectra. In fact, if the authors detect, respectively, the fluorescence emission
      spectra of pure Eu3+ solutions and the UV-Vis absorbance spectra of pure Nd3+
      solutions, then use these spectra data to construct a series of synthesized
      spectra of an assumed mixture solution in which Eu3+ and Nd3+ are not mixed
      together, because Eu3+ and Nd3+ ions are spatially separated, there are no
      intermolecular interactions that should have occurred. Therefore, there are no
      cross-peaks that can be observed in the comparative 2D synchronous spectra. The
      cross peaks in 2D synchronous correlation spectra gives out a new approach to
      characterizing energy transfer among different lanthanide ions during the
      luminescence process.

PMID- 20672598
TI  - [Study on estimation of radiation dose using FTIR in mice thymus].
AB  - Fourier transform infrared spectroscopy (FTIR) was applied to study the
      biochemical changes in the radiation damaged mouse thymus which increased with
      radiation dose and provided a new method for the estimation of the radiation dose
      of radiation damaged patients. The results demonstrated that with the dose
      increasing, the peak positions like 1 550, 1 400, 1 400 and 1 640 cm(-1) at the
      dose of 2, 3 and 5 Gy showed some difference, and there was obvious variance in
      the intensity: (1) The intensity ratio of 1 085 to 1 236 cm(-1) related to
      nucleic acid tended to decrease. (2) The intensity ratio of 1 640/1 550
      decreased. (3) The intensity at 2 958, 2 925, 1 460 and 1 400 cm(-1) showed no
      significant difference. The results suggest that it may be possible for FTIR to
      become an effective method to estimate the radiation dose in clinic.

PMID- 20672599
TI  - [Ionization energies and infrared spectra studies of histidine using density
      functional theory].
AB  - Histidines provide axial ligands to the primary electron donors in photosynthetic
      reaction centers (RCs) and play an important role in the protein environments of
      these donors. In this paper the authors present a systematic study of ionization
      energies and vibrational properties of histidine using hybrid density functional
      theory (DFT). All calculations were undertaken by using B3LYP method in
      combination with four basis sets: 6-31G(d), 6-31G(df, p), 6-31+G(d) and 6
      311+G(2d, 2p) with the aim to investigate how the basis sets influence the
      calculation results. To investigate solvent effects and gain a detailed
      understanding of marker bands of histidine, the ionization energies of histidine
      and the vibrational frequencies of histidine which are unlabeled and 13C, 15N,
      and 2H labeled in the gas phase, CCl4, protein environment, THF and water
      solution, which span a wide range of dielectric constant, were also calculated.
      Our results showed that: (1) The main geometry parameters of histidine were
      impacted by basis sets and mediums, and C2-N3 and N3-C4 bond of imidazole ring of
      histidine side chain display the maximum bond lengths in the gas phase; (2)
      single point energies and frequencies calculated were decreased while ionization
      energies increased with the increasing level of basis sets and diffuse function
      applied in the same solvent; (3) with the same computational method, the higher
      the dielectric constant of the solvent used, the lower the ionization energy and
      vibrational frequency and the higher the intensity obtained. In addition,
      calculated ionization energy in the gas phase and marker bands of histidine as
      well as frequency shift upon 13C and 15N labeling at the computationally more
      expensive 6-311+G(2d, 2p) level are in good agreement with experimental
      observations available in literatures. All calculations indicated that the
      results calculated by using higher level basis set with diffuse function were
      more accurate and closer to the experimental value. In conclusion, the results
      provide useful information for the further studies of the functional and
      vibrational properties of chlorophyll-a ligated to histidine residue in
      photosynthetic reaction center.

PMID- 20672600
TI  - [The IR spectroscopic study of hydrothermal synthetic KTP].
AB  - In the present paper, different-generation hydrothermally grown KTP crystals were
      tested by the Nicolet 550 type FIR spectrometer with the reflective technique.
      They were studied on different crystal faces. Since the hydrothermally grown KTP
      crystal usually grows (100), (011) and (201) crystal faces, these faces were
      tested in different-generation products, and they were tested by two spectral
      wave bands, 2 000-4 000 and 400-2 000 cm(-1). The figures were compared with the
      flux-melt grown KTP crystal. In addition, making reference to the method of
      calculation about the consistence of OH- in quartz, the consistence of OH- in
      different -generation hydrothermally grown KTP crystals was estimated. In the
      hydrothermal grown KTP crystals, the stretching vibration of OH- shows distinct
      directivity characteristic. The absorption at [100] direction is obvious and the
      frequency is about 30 cm(-1) higher than the flux-melt grown KTP. Each new
      generation weakened the consistency of OH-, which restrained the growth of the
      KTP crystal. Accordingly, increasing the purity of rough materials plays a very
      important role in improving the quality of the crystals.

PMID- 20672601
TI  - [Study on the characteristic peaks of infrared spectra from Ganoderma lucidums].
AB  - Infrared spectroscopy and dual-indicator sequence were used to study their IR
      characteristic peaks of Ganoderma lucidums from different places and species. The
      experimental results showed that the majority of Ganoderma lucidum from different
      places and species had the similar characteristic peaks of infrared spectra,
      Their common peak ratio could reach more than 91.67%, but the common peak ratio
      of mycelium was 52.94%-58.82%, and variant peak ratio was 29.41%-66.67%. The main
      variation peak was in the fingerprint regions 1 460.9-1 423.7 cm(-1) with ladder
      peaks. The IR characteristic peaks of Ganoderma lucidum obviously appear as the
      main characteristic peaks with the type of polysaccharide and protein bands.
      There was obviously a wide and strong absorption peak in 3 377.8-3 396.5 cm(-1),
      a small acromion in 2 924.2-2 925.1 cm(-1), a medium intensity absorption peak in
      1 635.8-1 650.3 and 1 372.5-1 375.2 cm(-1), a strong absorption bifurcate peak in
      1 074.8-1 075.3 and 1 043.2-1 045.2 cm(-1), a obvious weak peak in fingerprint
      regions 891.0-894.8 cm(-1), and a medium intensity absorption peak in 563.10
      574.7 cm(-1).

PMID- 20672602
TI  - [Extending hemicelluloses content calibration of Acacia spp using NIR to new
      sites].
AB  - In this research, hemicellulose contents of 78 wood meal samples of Acacia spp
      trees grown in Guangxi and another 33 wood meal samples of Acacia spp trees grown
      in Fujian were measured by wet chemistry. NIR spectra were also collected by a
      Bruker MPA spectrometer within 4 000-12 500 cm(-1) of wavenumbers using a
      standard sample cup. Equations were developed using partial least squares (PLS)
      regression and cross validation for multivariate calibration in this study. High
      coefficients of determination (R2) and low root mean square errors of cross
      validation (RMSECV) were obtained for hemicellulose content (R2 = 0.947, RMSECV =
      0.464) of Guangxi woodmeal samples. Prediction produced high correlation
      coefficients between laboratory and predicted values, with R2 and RMSEP values
      being 0.925 and 0.455, respectively. A variable numbers of Fujian samples ranging
      from one to thirteen were used to enhance the Guangxi calibration so as to be
      widely used for routine assessment of wood chemistry. It was demonstrated that
      the addition of a single Fujian sample to the Guangxi calibration set was
      sufficient to greatly reduce predictive errors and that the inclusion of 3 Fujian
      samples in the Guangxi set was sufficient to give relatively stable predictive
      errors. The R2 is 0.904 and RMSEP is 0.759. The addition of different sets of 3
      Fujian samples to the Guangxi calibration, however, caused predictive errors to
      vary between sets.

PMID- 20672603
TI  - [Analysis of soil humus and components after 26 years' fertilization by infrared
      spectroscopy method].
AB  - The infrared spectrum was used to discuss structure change of soil humus and
      components of chemical groups in soil humic acids (HA) and fulvic acids (FA)
      isolated from soils in different fertilization treatment after 26 year's
      fertilization. The result indicated that using the infrared spectroscopy method
      for the determination of humus, humus fractions (HA and FA) and their structure
      is feasible. Fertilization affected the structure and content of soil humus and
      aromatization degree. After 26 years' fertilization, the infrared spectrum shapes
      with different treatments are similar, but the characteristic peak intensity is
      obviously different, which reflects the effects of different fertilization
      treatments on the structure and amounts of soil humus or functional groups.
      Compared with no fertilization, little molecule saccharides decreased and aryl
      groups increased under application of inorganic fertilizer or combined
      application of organic and chemical fertilizer. The effect was greater in
      Treatment NPK and M+NPK than in Treatment M1 N and M2 N. Organic and NPK
      fertilizer increased the development of soil and increased soil quality to a
      certain extent. Results showed that organic fertilization increased aromatization
      degree of soil humus and humus fractions distinctly. The authors could estimate
      soil humus evolvement of different fertilization with infrared spectroscopy.

PMID- 20672604
TI  - [Study on the application of ridge regression to near-infrared spectroscopy
      quantitative analysis and optimum wavelength selection].
AB  - In the present paper, taking 66 wheat samples for testing materials, ridge
      regression technology in near-infrared (NIR) spectroscopy quantitative analysis
      was researched. The NIR-ridge regression model for determination of protein
      content was established by NIR spectral data of 44 wheat samples to predict the
      protein content of the other 22 samples. The average relative error was 0.015 18
      between the predictive results and Kjeldahl's values (chemical analysis values).
      And the predictive results were compared with those values derived through
      partial least squares (PLS) method, showing that ridge regression method was
      deserved to be chosen for NIR spectroscopy quantitative analysis. Furthermore, in
      order to reduce the disturbance to predictive capacity of the quantitative
      analysis model resulting from irrelevant information, one effective way is to
      screen the wavelength information. In order to select the spectral information
      with more content information and stronger relativity with the composition or the
      nature of the samples to improve the model's predictive accuracy, ridge
      regression was used to select wavelength information in this paper. The NIR-ridge
      regression model was established with the spectral information at 4 wavelength
      points, which were selected from 1 297 wavelength points, to predict the protein
      content of the 22 samples. The average relative error was 0.013 7 and the
      correlation coefficient reached 0.981 7 between the predictive results and
      Kjeldahl's values. The results showed that ridge regression was able to screen
      the essential wavelength information from a large amount of spectral information.
      It not only can simplify the model and effectively reduce the disturbance
      resulting from collinearity information, but also has practical significance for
      designing special NIR analysis instrument for analyzing specific component in
      some special samples.

PMID- 20672605
TI  - [Application of FTIR spectroscopy to the identification of Glycyrrhiza uralensis
      Fisch].
AB  - Fourier transform infrared spectroscopy with a spectra range of 4 000-400 cm(-1)
      was used to identify fifty nine samples of wild or cultivated Glycyrrhiza
      uralensis Fisch. from six different places around China. The 1D spectra and their
      second derivative spectra of herbal samples, the corresponding extract samples
      and two marker compounds (glycyrrhizic acid and liquiritin) were compared. The
      wide peak in 1 100-1 000 cm(-1) was used to identify the components of
      polysaccharide; the peak at 1 318 cm(-1) mainly belonged to calcium oxalate; the
      peaks at 1 745 and 1 386 cm(-1) were used to assess the content of glycyrrhizic
      acid; the peaks at 1 612 and 1 512 cm(-1) were the characteristic peaks of
      liquiritin. The intensity of characteristic peaks can represent the content of
      corresponding compound. The horizontal and vertical comparisons of all herbal
      samples showed that the characteristic peaks of wild samples were strong, and all
      wild samples had the similar quality; the characteristic peaks of cultivated
      samples were weaker than those of the wilds; the ages of glycyrrhiza had great
      effect on the quality of samples.

PMID- 20672606
TI  - [The enhancement of 1.5 microm near infrared luminescence in Er3+ and Yb3+
      codoped Y2O3 nanocrystalline].
AB  - Y0.96 Er0.02 Yb0.02)O3 nanocrystals of 10 and 40 nm average particle size were
      prepared by combustion method. And bulk materials of the same components were
      obtained by annealing at 1 200 degrees C. X-ray diffraction (XRD), Fourier
      transform infrared (FTIR) spectra, transmission electron microscope (TEM), and
      scanning electron microscopy (SEM) were used to characterize the crystal
      structure and morphology of the samples. The upconversion emission spectra and
      NIR (near-infrared) emission spectra were measured, under 980 nm excitation. The
      research result indicates that as the particle size decreases, the upconversion
      red emission and NIR emission components increase in the emission spectra. This
      phenomenon is attributed to the large ratio of surface area to volume in
      nanocrystals. This characteristic makes the nanocrystals absorb more OH-, whose
      vibrational energy is 3 200-3 800 cm(-1). The increase in the OH- number enhances
      the rate of nonradiative relaxation from Er3+ 4I11/2 to 4I13/2 energy level
      (energy gap is 3 600 cm(-1)). This nonradiative relaxation process depopulates
      the 4I11/2 level and makes the green emission weaker. Meanwhile, this process
      populates the 4I3/2 level and makes the red and NIR emissions stronger. The
      intensity of 1.5 microm main peak is 1.6 times that of bulk materials. This
      result has great significance in actual applications of nanophosphors.

PMID- 20672607
TI  - [Study of nondestructive and fast identification of fabric fibers using near
      infrared spectroscopy].
AB  - A fast and nondestructive identification method to distinguish different types of
      fabric fibers is proposed in the present paper. A total of 214 fabric fiber
      samples, including wool, cashmere, terylene, polyamide, polyurethane, silk, flax,
      linen, cotton, viscose, cotton-flax blending, terylene-cotton blending, and wool
      cashmere blending, were collected from Beijing Textile Fibre Inspection
      Institute. They contain yarns, raw wool or cashmere, and various fabric straps
      with different colors and different braid patterns. Sample presentation for
      measuring near infrared spectra of various textile fibers was tried to reduce the
      impact from the ununiformity of polymorphous fabric structure. Spectral data were
      pretreated using multiplicative signal correction (MSC) to reduce the influence
      of spectral noise and baseline shift. Classification of 12 kinds of fabric fibers
      in various braid patterns was studied using minimum spanning tree method and soft
      independent modeling of class analogy (SIMCA) classification based on principal
      component analysis of NIR spectra. The minimum spanning tree for the spectra of
      total samples shows that the samples in the same type fall almost into one
      cluster, but there are overlaps between some two different clusters of fabric
      fibers with very similar chemical compositions, such as wool and cashmere.
      Complete discrimination between cashmere and wool has been achieved using SIMCA.
      The results show that nondestructive and fast identification of fabric fibers
      using near infrared spectral technique is potentially feasible.

PMID- 20672608
TI  - [Real-time monitoring of industrial acetic acid production process using a new
      type of online NIR analysis system].
AB  - The safe and real-time monitoring of the production process of acetic acid is
      always a key technical problem. The conventional online chromatographic analysis
      can't satisfy the requirements of real-time analysis for its inherent
      disadvantages. A new type of on-line near-infrared analysis system has been
      developed for real-time analysis of the concentration of each component in acetic
      acid reaction kettles instantly. Its features and configuration were described in
      detail. Both the laboratory modeling and field application results have confirmed
      that this system is of high stability and accuracy. The proposed system can
      effectively solve the key technical problems in the manufacture and ensure the
      safety and stability of production process of acetic acid.

PMID- 20672609
TI  - [Discriminant analysis of raw milk adulterated with botanical filling material
      using near infrared spectroscopy].
AB  - In order to find out a fast measure method of adulterated milk based on near
      infrared spectroscopy, milk adulterated with plant butter, vegetable protein and
      starch was collected respectively. Using Fourier transform near infrared
      spectroscopy to scan the samples, the spectrum data were obtained. The samples
      were scanned in the spectral region between 4 000 and 12 000 cm(-1) by FT-NIR
      spectrometer with an optic fiber of 2 mm path-length and an InGaAs detector. Then
      all data were analyzed by principal component analysis combined with Fisher line
      discriminant analysis (FLDA) and partial least squares (PLS). Results show that
      the accumulative reliabilities of the first six components were more than 99%, so
      the first six components were applied as FLDA inputs and the values of the type
      of milk were applied as the outputs. An adulterated milk qualitative discriminant
      model based on Fisher line discriminant analysis was developed finally. The
      result indicated that the accuracy of detection of calibration samples is 97.78%.
      The unknown test samples were tested by this model and the correct identification
      rate is 94.44%. Partial least square models for detecting the content of material
      added to raw milk were set up with good veracity. The predictive correlation
      coefficient (R2) of calibration sets of milk adulterated with plant butter,
      vegetable protein and starch are 99.08%, 99.96% and 99.39%, respectively, while
      the root mean square errors of cross validation (RMSECV) of the three calibration
      sets are 0.304%, 0.013 5% and 0.060%, respectively. The R2 of validation sets of
      the three kinds of adulterated milk are 98.50%, 99.94% and 98.50%, respectively,
      while the root mean square errors of prediction (RMSEP) of the three validation
      sets are 0.323%, 0.028 8% and 0.068%, respectively. All of these suggested that
      near infrared spectroscopy has good potential for rapid qualitative and
      quantitative detection of milk adulterated with botanical filling material.

PMID- 20672610
TI  - [Applications of near infrared reflectance spectroscopy technique to
      determination of forage mycotoxins].
AB  - The near infrared reflectance spectroscopy technique (NIRS) has been explored at
      many fields such as agriculture, food, chemical, medicine, and so on, due to its
      rapid, effective, non-destructive, and on-line characteristics. Fungi invasion in
      forage materials during processing and storage would generate mycotoxins, which
      were harmful for people and animal through food chains. The determination of
      mycotoxins included the overelaborated pretreatments such as milling, extracting,
      chromatography and subsequent process such as enzyme linked immunosorbent assay,
      high performance liquid chromatography, and thin layer chromatography. The
      authors hope that high precision and low detection limit spectrum instrument, and
      software technology and calibration model of mycotoxins determination, will fast
      measure accurately the quality and quantity of mycotoxins, which will provide
      basis for reasonable process and utilization of forage and promote the
      application of NIRS in the safety livestock product.

PMID- 20672611
TI  - [Fast discrimination of commerical corn varieties based on near infrared
      spectra].
AB  - The existing methods for the discrimination of varieties of commodity corn seed
      are unable to process batch data and speed up identification, and very time
      consuming and costly. The present paper developed a new approach to the fast
      discrimination of varieties of commodity corn by means of near infrared spectral
      data. Firstly, the experiment obtained spectral data of 37 varieties of commodity
      corn seed with the Fourier transform near infrared spectrometer in the wavenumber
      range from 4 000 to 12 000 cm(-1). Secondly, the original data were pretreated
      using statistics method of normalization in order to eliminate noise and improve
      the efficiency of models. Thirdly, a new way based on sample standard deviation
      was used to select the characteristic spectral regions, and it can search very
      different wavenumbers among all wavenumbers and reduce the amount of data in
      part. Fourthly, principal component analysis (PCA) was used to compress spectral
      data into several variables, and the cumulate reliabilities of the first ten
      components were more than 99.98%. Finally, according to the first ten components,
      recognition models were established based on BPR. For every 25 samples in each
      variety, 15 samples were randomly selected as the training set. The remaining 10
      samples of the same variety were used as the first testing set, and all the 900
      samples of the other varieties were used as the second testing set. Calculation
      results showed that the average correctness recognition rate of the 37 varieties
      of corn seed was 94.3%. Testing results indicate that the discrimination method
      had higher precision than the discrimination of various kinds of commodity corn
      seed. In short, it is feasible to discriminate various varieties of commodity
      corn seed based on near infrared spectroscopy and BPR.

PMID- 20672612
TI  - [Study of rotator phase and phase transition of short-chain alkane by means of
      Raman spectroscopy].
AB  - Raman spectroscopy was used to investigate the phase transition of n-hexacosane
      for real-time cooling run. In the cooling process, the n-hexacosane experienced
      the melt phase --> rotator phase --> monoclinic crystal phase transition. The
      changes in band intensity and frequency in the CH2 bending, CH2 twisting,
      skeletal C-C stretching, and CH3 rocking regions were mainly analyzed in order to
      know the changing sequence and process of these vibrational modes, and to reflect
      the relationship between these vibrational modes and molecular structure.
      Besides, the changes in band intensity and frequency revealed both transitions,
      particularly when using band components related to gauche bonds. Our research
      shows that Raman spectroscopy is an effective tool to monitor the phase
      transition of n-alkanes or even long-chain polymers. In addition, by analyzing
      the Raman peaks in 800-1 500 cm(-1) in the cooling process of n-hexacosane, the
      temperature range of rotator phase was obtained, proving that Raman spectroscopy
      can be used to observe the rotator phase occurring during the phase transition of
      paraffin.

PMID- 20672613
TI  - [Raman spectrum study on synthesis mechanism of porous ZnO microspheres assisted
      with trisodium citrate].
AB  - Raman spectrum was applied to analyze the synthesis mechanism of nanostructure
      porous ZnO microspheres prepared via hydrothermal method assisted with trisodium
      citrate. The Raman spectrum characteristics of the sample revealed that the ZnO
      microspheres contained Zn-citrate complex, which was the complex of citrate acid
      group and Zn2+ in the reaction solution. The complex was chemisorbed on (204) and
      (503) faces of the Zn(OH)2 crystallite in the reacting solution, resulting in
      Zn(OH)2 nanosheet from the crystallite. Large quantities of Zn(OH)2 nanosheets
      aggregated as porous microspheres in hydrothermal process. Zn-citrate complex
      chemisorbed on the nanosheet improved the thermal stability of Zn(OH)2, which
      means a decomposition temperature over 200 degrees C. Nanostructure porous ZnO
      microspheres were obtained by heating Zn(OH)2 microspheres at 300 degrees C and
      the nanosheet structure was maintained.

PMID- 20672614
TI  - [A study of phonon vibration like modes for aggregation structure in silicate
      melts by high temperature Raman spectrum].
AB  - Silicate melts are special fractal dimension system that is metastable state of
      near-way order and far-way disorder. In this paper, the size of nanometer
      aggregation structure and the frequences of phonon vibration like mode in the low
      dimension silicate series (CaO-Al2O3-SiO2 and Na2-Al2O3-SiO2 series) synthesized
      via high temperature melting and sol gel methods were measured by means of small
      angle X-ray scattering (SAXS), low wavenumber Raman spectrum (LWRS) and high
      temperature Raman spectrum (HTRS in situ measuring). The nanometer self
      similarity aggregation structure(it's size is about a few nm to a few tens nm)
      and phonic phonon vibration like modes of low temperature silicate gel, high
      temperature silicate melts and it's quenching glasses phases were obtained. So a
      quantitative method by HTRS for measuring the aggregation size in the high
      temperature melts was established. The results showed that the aggregation size
      of the silicate melts is smaller at high temperature than at room temperature and
      the number of bridge oxygen in one Si-O tetrahedron in network structure units is
      decreasing at high temperature. This study work provides important theory and
      information for deliberating geochemistry characteristic, crystallization &
      evolution of natural magma and enhancing performance of low dimension silicate
      matelials.

PMID- 20672615
TI  - [Study on real-time imaging of single stretched DNA molecules by total internal
      reflection fluorescence microscopy].
AB  - Total internal reflection fluorescence microscopy (TIRF) is a powerful tool for
      single molecule study, since only a thin layer of about 200 nanometers is excited
      by the evanescent wave, resulting in high sensitivity of detection and high
      signal-to-noise ratio of images. Molecular combing is a convenient and efficient
      way to stretch DNA molecules with the help of the binding force between DNA
      molecule and solid surface, as well as the lateral force introduced by ambient
      fluid flow. In the present paper, real-time fluorescence imaging of single DNA
      molecules was carried out with these two techniques. Clear images of single
      stretched DNA were obtained, while photocleavage of DNA-YOYO-1 complex was found
      to be naturally avoided under TIRF imaging conditions. Photobleaching of the
      complexes was investigated in real-time, and was greatly reduced by synchronizing
      the excitation of light (laser) and the exposure of detector (ICCD). The method
      optimized the experimental conditions for long-lasting real-time observation and
      imaging of single stretched DNA molecules, so as to lay a foundation for visually
      studying the kinetic processes of interactions between DNA and proteins.

PMID- 20672616
TI  - [Excitation-emission fluorescence characterization study of the three phenolic
      compounds].
AB  - The fluorescence intensity information was collected by scanning its fluorescence
      spectra at different excitation wavelengths. Based on its high sensitivity and
      selectivity, excitation-emission fluorescence can be widely used for detection of
      pollutants in the environment. The characterizations of the three phenolic
      compounds were investigated by this method, and the fluorescence peaks of phenol,
      m-cresol and thymol were confirmed at 272/300 nm, 274/300 nm and 276/304 nm when
      the excitation and emission wavelength were set in the range of 240-360 nm and
      260-500 nm respectively. The excitation and emission spectra of the three
      phenolic compounds are very similar because of their analogical structure. The
      intensity of the spectrum has a good linear relationship with the concentration
      when the solution concentration is between 0.02 and 1.0 mg x L(-1), and the
      limits of detection can reach at 1 microg x L(-1). Results show that the three
      compounds can be analyzed qualitatively and quantitatively by excitation-emission
      fluorescence.

PMID- 20672617
TI  - [Research on the 3D fluorescence spectra differentiation of phytoplankton by
      coiflet2 wavelet].
AB  - In the present paper, the authors utilize the wavelet base function coiflet2
      (coif2) to analyze the 3D fluorescence spectra of 37 phytoplankton species
      belonging to 30 genera of 7 divisions, and these phytoplankton species include
      common species frequently causing harmful algal blooms and most predominant algal
      species in the inshore area of China Sea. After the Rayleigh and Raman scattering
      peaks were removed by the Delaunay triangulation interpolation, the fluorescence
      spectra of those phytoplankton species were transformed with the coiflet2
      wavelet, and the scale vectors and the wavelet vectors were candidate for the
      feature spectra. Based on the testing results by Bayesian analysis, the 3rd scale
      vectors were the best feature segments at the division level and picked out as
      the fluorescence division feature spectra of those phytoplankton species, and the
      group of the 3rd scale vectors, the 2nd and 3rd wavelet vectors were the best
      feature segments at the genus level and chosen as the fluorescent genus feature
      spectra of those phytoplankton species. The reference spectra of those
      phytoplankton species at the division level and that at the genus level were
      obtained from these feature spectra by cluster analysis, respectively. The
      reference spectra base for 37 phytoplankton species was composed of 107 reference
      spectra at the division level and 155 ones at the genus level. Based on this
      reference spectra base, a fluorometric discriminating method for phytoplankton
      populations was established by multiple linear regression resolved by the
      nonnegative least squares. For 1 776 samples of single phytoplankton species, a
      correct discriminating rate of 97.0% at genus level and 98.1% at division level
      can be obtained; The correct discriminating rates are more than 92.7% at the
      genus level and more than 94.8% at the division level for 384 mixed samples from
      two phytoplankton species.

PMID- 20672618
TI  - [Determination of antibiotics residues in the raw fresh milk of farms in the
      Miyun County of Beijing with Mg2+ -sensitized metacycline fluorescence
      microscopic imaging technique].
AB  - Mg(2+) -sensitized metacycline fluorescence microscopic imaging technique was
      applied to detect the raw fresh milk of four cows breeding farms in the Miyun
      County of Beijing based on the capillary effect of solvent on solid supports. In
      the presence of NH3-NH4 Cl buffer solution (pH 9.99) and PVA-124, Mg2+ and
      metacycline can form a strong fluorescence complex of 1 : 1, and Mg(2+) 
      metacycline complex can form an SOR on the hydrophobic supports with the diameter
      of 0.93 mm and its ring belt width of 26.2 microm. By measuring the fluorescence
      intensity of the ring, the quantitative analysis of metacycline was achieved with
      the detection limit (3sigma) of 8.8 x 10(-14) mol x ring(-1) (1.8 x 10(-7) mol x
      L(-1)) and linear range of 2.2 x 10(-13) -3.6 x 10(-12) mol x ring(-1) (4.4 x 10(
      7) -7.2 x 10(-6) mol x L(-1)) when 0.50 microL droplet was spotted. This method
      has been satisfactorily applied to the determination of metacycline in the raw
      fresh milk samples with the recovery of 93.8%-108% and RSD less than 4.3%.

PMID- 20672619
TI  - [Study on the elements of the fluorescence spectra emitted from ethanol-water
      mixture].
AB  - The 236 nm UV-light was adopted to excite the 10 ethanol-water mixture samples in
      which the volume percent of ethanol ranges from 10% to 95%, and the Gaussian
      decomposition method was used to decompose the fluorescence spectra obtained
      above to Gaussian curves, where every Gaussian curve can be attributed to the
      fluorescence emission of a certain kind of luminescent ethanol-water cluster,
      which is formed by the association between water molecules and ethanol molecules.
      It was found that every spectrum of the certain binary mixture contains 8
      Gaussian elements, and the emission density and peak wavelength of each element
      were also obtained. The authors studied the mechanism of the fluorescence
      emission of the mixtures based on the structural characters of fluorescence
      substances and concluded that the water molecules play an important role in the
      fluorescence emission: they enlarge the conjugate system as the electron donors;
      they bridge the ethanol molecules to form 8 kinds of new clusters at the same
      time, and the conformation of the clusters is rings and chains composed by
      several rings. Through the peak wavelengths of the Gaussian elements decomposed
      from the certain concentration spectrum the authors got the information about the
      relative size of the new clusters, i.e. the clusters are bigger or show chain
      structures when the peak wavelength of the Gaussian curves is located at the
      longer positions. The emission transition energies of the 8 kinds of new clusters
      were also calculated. In addition, it was found that there was a certain relation
      between the half-width and the association situation. The research contributes to
      the study of ethanol-water cluster structures and their physical and chemical
      characteristics.

PMID- 20672620
TI  - [Characterization of biocompatible CdTe/znte quantum dots and its application in
      cell labeling].
AB  - Water-soluble CdTe/ZnTe core-shell quantum dots (QDs) coated with L-cysteine were
      synthesized in low-temperature aqueous-phase one-pot approach. The authors
      measured the spectral characteristics of QDs at different pH in various buffer
      solutions and under different excitation laser powers. The primary results show
      that the absorption spectra of QDs approximately overlap and the fluorescence
      spectra peaks have no shift in different pH solution. The fluorescence intensity
      increased linearly with increasing pH. With the incubation time in borate buffer
      solution, the fluorescence intensity decreased a little. Under strong power
      laser, the QDs were photobleached rapidly. However, QDs are strongly anti
      photobleaching under appropriate laser power (< 100 microW). Thus, such QDs have
      good biological stability and optical stability. By conjugating the QDs with
      transferrin protein and constructing the targeted fluorescent nanoparticles, the
      authors labelled the HeLa cell successfully. Photobleaching experiments in vivo
      show that microenvironment inside cells affect the stability and accelerate the
      photobleaching of QDs.

PMID- 20672621
TI  - [Development of citrus yield prediction model based on airborne hyperspectral
      imaging].
AB  - The phenomenon of alternate bearing of fruits seriously affects the fruit yields
      as well as the economic benefits of orchards. The present study investigated the
      possibility of airborne hyperspectral images to predict the fruit yield of
      individual citrus trees. The hyperspectral data were first extracted from the
      images and the predictors were determined using partial least-squares regression
      (PLS). The optimal number of PLS factors were identified, and they were used as
      inputs of citrus yield prediction models developed by means of multiple linear
      regression (MLR) and artificial neural network (ANN) modelling techniques. The
      results showed that the models based on the hyperspectral images obtained in May
      achieved the best prediction, and the PLS-MLR model has a better stability and
      consistency than the PLS-ANN model. These results provide an important
      theoretical and technical foundation for the future research and development of
      hyperspectral imaging-based citrus production techniques.

PMID- 20672622
TI  - [Spectral characters analysis of ground objects in snowmelt period in the
      northern slope of Tianshan Mountains].
AB  - Urumqi River Basin and Juntanghu Basin, located in the northern slope of Tianshan
      Mountains in Xinjiang, were selected as typical study areas. With the portable
      field spectrometer CI700 produced by CID in the United States and from a large
      number of field investigations and field measurements in the snowmelt period
      (usually starts in the end of February or the beginning of March, and goes on for
      many days) from 2006 to 2009, a variety of spectral curves and their variation of
      typical ground objects in the snowmelt period in the northern slope of Tianshan
      Mountains, such as snow, ice, water and soil, were obtained, and spectral
      characters analysis was carried out based on the collected data. The results
      showed that the classes of ground objects in snowmelt period are quite monotone,
      however, a great challenge was brought about to the quantitative remote sensing
      research on surface parameters in snowmelt period because of the interactive
      effects of the complex systems of snow-ice-water-soil, the spectral properties of
      typical ground objects, and their complex changes. Reflectance of soil with
      different moisture conditions is distinct, as well as reflectance of ice and snow
      under different environment or dissimilar mixtures have obvious development
      trends. The series of observations and analysis of the typical and complex
      spectral features in snowmelt period are of great significance for the
      fundamental study of objects' spectral characteristics, as well as for the
      application of quantitative remote sensing studies.

PMID- 20672623
TI  - [A new probe for Ca2+ based on the rhodamine B amide armed homotrioxacalix[3]
      arene-Sb3+ complex].
AB  - A new fluorescence probe based on the rhodamine B amide-armed
      homotrioxacalix[3]arene (1) has been synthesized, and its Ca(2+)-selective
      chromogenic properties were investigated in acetonitrile Tris-HCl buffer (pH 7)
      solution by UV-Vis and fluorescence spectroscopies. Upon the addition of Sb3+
      ion, the spirocyclic ring of 1 was opened and a significant fluorescence
      enhancement and colorimetric change was observed. However, addition of Ca2+ ion
      to the solution of 1-Sb3+ complex leads to a strong fluorescence quenching of the
      original 1-Sb3+ complex. The phenomenon exhibited a pronounced Ca2+ selective
      fluoroionophoric behavior over other coexistent metal ions and provided the
      ratiometric determination as well as naked-eye detection of Ca2+ ions.

PMID- 20672624
TI  - [A path-length correction method on biochemical parameter nondestructive
      measuring of folium].
AB  - Vis/NIR spectroscopy technology is capable of analyzing the content of
      biochemical parameter in folium rapidly and nondestructively. In the process of
      spectrum analysis, the variations in path-length between different samples exist,
      with the random light scattering and leaf thickness perturbations, which
      influence the precision of quantitative analysis model. In order to resolve this
      problem, an improved path-length correction method based on Extended
      Multiplicative Scattering Correction is presented. In this paper, firstly the
      theory of EMSC algorithm is deduced. EMSC method incorporates both chemical terms
      and wavelength functions to help realize the efficient separation of path-length
      and interest concentration. Secondly two experiments were implemented to
      demonstrate the validity of the method. In Experiment 1, sixteen samples of
      different thickness but almost the same chlorophyll content were selected, and
      how the path-length affects the spectrum was compared, after EMSC preprocessing,
      the variable coefficient of spectrum could approach the repeatability error of
      spectrometer. In Experiment 2, thirty-two samples of different thickness and
      chlorophyll content were selected. PLS model established using cross validation
      was employed to evaluate the efficiency of the presented algorithm. Before the
      preprocessing, the root mean squared error of prediction is 3.9 SPAD with 5
      principal components. After preprocessing, the predicted root mean squared error
      is 2.2 SPAD with 12 principal components. The results indicate that the improved
      EMSC preprocessing method could exactly eliminate the spectrum difference caused
      by the path-length variations between different foliums, enhance the sensitivity
      of concentration and spectral data, and increase the precision of calibrated
      model.

PMID- 20672625
TI  - [A rapid quantificational identification model of minerals and its applications].
AB  - Rapid identification of minerals is the key point for enhancing the efficiency of
      mineral exploration by remote sensing, mineral mapping by remote sensing and many
      geological investigations. Because of the limitation of technology and other
      aspects, the amount of models and software concerning rapid identification of
      minerals is very small. Since 1990s the development in spectrometers and
      computers has made it possible to apply near infrared spectrum technology to
      identify minerals. Two models have emerged. Model I is based on analyzing the
      position of absorption bands, while Model II is founded on waveform matching. In
      the present paper, characteristic spectrum linear inversion modeling was built.
      Validated by the data gained from end-members of USGS mineral spectrum library by
      mixing randomly, this model with the accuracy being approximately 100% is much
      better than Model I and II. Used to analyze the 23 samples selected in Baogutu
      area in Xinjiang, the model we built with the accuracy of 64.6% is superior to
      Model I (the accuracy is 33.8%) and Model II (the accuracy is 8.1%). Though the
      accuracy of our model is not as high as that of identification by microscope at
      present, using our model is much more effective and convenient, and there also
      will be less artificial error and smaller workload. The good performance of our
      model in the mineral exploration work by remote sensing in Baogutu area in
      Xinjiang shows wide popularizing prospects.

PMID- 20672626
TI  - [Study on the geochemical anomaly of copper element based on reflectance
      spectra].
AB  - In order to explore the feasibility of studying the geochemical anomaly of copper
      element by using remote sensing method, the correlation between Cu and other
      elements and the correlation between Cu and reflectance spectra were analyzed
      based on the element contents and the reflectance spectra of rock samples. It was
      found that Fe is most highly correlated with Cu, followed by Ti and As. The
      relationship between the Cu content and the reflectance spectra is of a negative
      correlation, and the higher the Cu content, the stronger the correlation.
      Furthermore, based on the reflectance spectra, the partial least squares
      regression of the Cu, Fe, Ti and As content was carried out respectively. The
      result shows that Ti gets the highest accuracy, followed by Fe. The worst is for
      As. Although the accuracy of the Cu model is not too high, it is feasible to
      establish an indirect model of copper anomaly on the basis of Fe model because of
      the strong correlation between them. In order to improve the accuracy of the
      model, some transformations for the reflectance spectra were performed and many
      spectral indices were acquired. Based on the spectral indices, the partial least
      squares regression of Fe was carried out. The accuracy of the regression model
      increased greatly. The highest correlation coefficient of the regression model is
      0.687 6 for the calibration samples and it is 0.595 9 for the validation samples.

PMID- 20672627
TI  - [Study on the interaction between DNR-D3 (daunorubicin derivative)and ctDNA by
      spectroscopic methods].
AB  - The interaction of DNR-D3 (daunorubicin derivative) synthesized in our laboratory
      with ctDNA was investigated by UV spectrum and fluorescence spectrum under
      physiological conditions (pH 7.4) for the first time. The red shifts and
      hypochromicities were observed from the absorption titration experiments. These
      results suggest that DNR-D3 was intercalated into the DNA base pairs. Through the
      fluorescence quenching data measured at different temperatures (20 degrees C, 30
      degrees C and 37 degrees C), it is known that the quenching mechanism of
      fluorescence of DNR-D3 by ctDNA is a static quenching type. On the other hand,
      the binding constant, the number of binding sites and thermodynamic parameters
      were also obtained. These data also indicate that the binding mode of the
      interaction between DNR-D3 and ctDNA is intercalation. Additionally, the types of
      interaction force are mainly hydrogen bonding and electrostatic interaction, and
      the binding is exothermic enthalpy-entropy cooperative driven process. When the
      degree of fluorescence quenching of DNR-D3 is 50%, the ratio of the molar
      concentration of DNR-D3 to ctDNA is 7/25, which indicates that the DNR-D3
      anthracycline was intercalated into the DNA base pairs and that DNR-D3 showed a
      strong anti-cancer activity. DNR-D3 is expected to become one of the drug
      candidates from our investigations.

PMID- 20672628
TI  - [Preparation of microencapsulated red phosphorus and its flame-retardant
      application in PP composites].
AB  - In the present study, the melamine-formaldehyde prepolymer (MFP) was first
      synthesized at pH 8-8.5 under about 80 degrees C with melamine, formaldehyde,
      triethanolamine and methanol as the starting materials. Subsequently, the
      microencapsulated red phosphorus (MRP) was successfully prepared by in-situ
      polymerization at pH 5.5 under 65 degrees C, using MFP and red phosphorus (RP)
      powders as raw materials, and potassium persulphate (KPS) as catalyst. The
      obtained products were detected by differential scan calorimetry (DSC), scanning
      electron microscope (SEM), Fourier transform infrared (FTIR) and X-ray photo
      electron spectroscopy (XPS). It was found that KPS is useful in enhancing the
      reaction activity of MFP, which can make RP be well encapsulated by melamine
      formaldehyde resin (MF) and reduce the reaction time. The DSC, SEM and XPS
      results show that it won't get well-encapsulated MRP only under acidic condition
      and without any KPS. When a proper quantity of KPS is employed, the RP particles
      can be almost completely-encapsulated by MF and the peak temperature of oxidation
      reaction for MRP is 480 degrees C, which is much higher than that of RP,
      extending the applications for MRP. The FTIR spectrum demonstrates that the
      coating material on the surface of RP accurately is MF, in agreement with the
      reference. Polyproplene (PP) composites with different formulations were prepared
      by melt extrusion. It was shown that the flame-retardant efficiencies are very
      low when the PP composites only contain MRP or MH. However, the flame-retardant
      property can obviously improve if MRP and MH are both used in the PP composites.
      When PP : MRP: MH = 100 (phr) : 15 (phr) : 50 (phr), the limited oxygen index of
      the MRP/MH/PP composite is 26%, and vertical firing ranks UL-94 V-0. In addition,
      the possible flame-retardant mechanism of the PP composites has also been
      discussed, and further verified by FTIR and Raman spectroscopy.

PMID- 20672629
TI  - [Research on remote sensing inversion biomass method based on the Suaeda salsa's
      measured spectrum].
AB  - Suaeda salsa is one of characteristic vegetation of wetlands in Northern China.
      By measuring the spectral data and leaf area index (LAI) of the Suaeda salsa in
      the ShuangTai Estuary of Liaodong Bay by the use of portable spectrometer and
      vegetation canopy analyzer, collecting the biomass of the Suaeda salsa samples,
      setting up the spectral reflectance curve of the Suaeda salsa, probing into the
      relationship between the vegetation index and the leaf area index of the Suaeda
      salsa, carrying out regression analysis of LAI and biomass and constructing the
      function equation, some conclusion were drawn: (1) By the end of September the
      spectral characteristics of Suaeda salsa show that at the red band 630 nm there
      is a clear reflection of the peak with a reflection rate of 12%-15%; there is a
      clear "red valley" configuration between 680 and 700 nm, and there is a clear
      "red edge" reflection rate of 25%-30% about 760 nm. (2) It was found that there
      is best correlation between vegetation index (SAVI and MSAVI) and LAI compared to
      other vegetation index in the regression analysis of the LAI and vegetation
      index. The correlation coefficient R2 is 0.711. By comparison of vegetation index
      linear regression equations, the correlation coefficient (SAVI and LADI) R2 is
      0.696; the value of R2 (LAI and MSAV) is 0.695; the value of R2 (RVI) is 0.664;
      the value of R2(NDVI) is 0.649 and the value of R2 (PVI) is 0.466. (3) The value
      of correlation coefficient is low between the biomass and the vegetation indexes
      (RVI and NDVI) and the value of linear regression equation's R2 is 0.342 and
      0.316, and the Logarithmic regression equation's R2 is 0.319 and 0.21, and the
      quadratic equation's R2 is 0.589 and 0.568, the value of correlation coefficient
      is high between the biomass and the vegetation indexes (PVI, SAVI and MSAVI), the
      value of linear regression equation is 0.626, 0.698 and 0.679, that of
      logarithmic regression equation is 0.592, 0.706 and 0.683 and that of the
      quadratic equation is 0.688, 0.711 and 0.683.

PMID- 20672630
TI  - [Synthesis and spectra of copper(I) bromide complex with N, N
      bis[(diphenylphosphino) methyl]-2-pyridinylamine].
AB  - A new ligand N, N-bis[(diphenylphosphino)methyl]-2-pyridinylamine (L) and its
      luminescent dinuclear copper(I) complex [CuBrL]1 (1) were synthesized and
      characterized by mass spectrometry, elemental analysis, NMR and electronic
      spectroscopies. The structure of complex 1 was determined by X-ray crystal
      analysis to be a dinuclear complex with a pseudo-tetrahedral geometry. The
      complex 1 crystallizes in a triclinic space group P-1 and has two copper(I )
      centers bridged by two halogen ligands to form the dinuclear structure with a
      four-membered Cu2 Br2 ring. The Cu-Cu distance in complex 1 is 0.306 0 nm which
      is longer than a sum of Van der Waals radius of two copper( I ) atoms. Therefore
      there is no substantial interaction between the two copper(I) centers in complex
      1. DFT calculations indicate that the electron density of HOMO is distributed
      mainly over the copper, bromine and phosphorus atoms, while that of LUMO is
      localized on the ligand. Our work shows that there are two mechanisms to form the
      the lowest excited state of complex 1, i.e. the metal-to-ligand charge transfer
      (MLCT) and halogen-to-ligand charge transfer (XLCT).

PMID- 20672631
TI  - [Effect of remotely sensed data errors on the retrieving accuracy of territorial
      parameters--a case study on chlorophyll a concentration inversion of Taihu Lake].
AB  - The errors of the territorial parameters retrieved from remote sensing are
      decided by the data error and the model error. The data error is not simply added
      to the total errors of retrieval results. It would be reformed by the
      quantitative inversion model, and then, combined with the model errors and melts
      into the totals errors. Accordingly, during the quantitative process, taking
      advantage of the highest correlation coefficient or the least root mean square
      error as assessment standard for describing the chlorophyll a concentration vs
      remote sensing parameters is not reasonable. Focusing on the above problem, the
      study pointed out that the reason why the result of the optimized cost function
      is contrary with the practical is that different model has different influence on
      data errors. Combined with the in situ measurements of Taihu Lake, in October,
      2003, it is known that due to the error magnification phenomena (TM2/TM3
      algorithm is 2.28 times more than TM2/TM1 algorithm), although the regression
      coefficient of TM2/TM3 algorithm is higher than TM2/TM1 algorithm, the
      quantitative errors of TM2/TM3 algorithm are 7.938 5 microg x L(-1) more than
      TM2/TM1 algorithm. Moreover, the retrieval results show that distribution pattern
      of the results of TM2/TM3 algorithm is completely opposite to the TM2/TM1
      algorithm. According to the former research achievements, the results of TM2/TM1
      algorithm would be more reasonable. In summary, only when that the factor of data
      error is added to the optimized cost function is taken as a constrain condition
      in search for the optimal solution of the quantitative models, would the
      retrieval results be more reliable.

PMID- 20672632
TI  - [An investigation of temperature compensation of HCL gas online monitoring based
      on TDLAS method].
AB  - HCL, with the character of strong erosion and toxicity, is a kind of chemical
      material of vital importance. So measuring the HCL in-situ can not only optimize
      its production process, but also be necessary to reduce the environment
      pollution. TDLAS (tunable diode laser absorption spectroscopy) technology, and
      owning the advantage of the tunability and narrow line width of the diode laser,
      this method can relatively easily select the absorption line of the detected gas
      without the interference from other gas, thus making the rapid and accurate HCL
      measurement possible. In the present paper, the HCL measurement system and the
      implemented experiment are introduced. The impact of the temperature on the
      measurement as well as the temperature compensation method is emphasized. The
      final experimental results validated the rationality of the empirical equation
      and therefore the improvement of the accuracy and feasibility of the TDLAS
      technology. The system, whose detection limitation reaches 2 ppm, can satisfy the
      needs of industrial in-sit measurement.

PMID- 20672633
TI  - [Identification of cucumber disease using hyperspectral imaging and discriminate
      analysis].
AB  - Hyperspectral imaging (400-720 nm) and discriminate analysis were investigated
      for the detection of normal and diseased cucumber leaf samples with powdery
      mildew (Sphaerotheca fuliginea), angular leaf spot (Pseudomopnas syringae), downy
      mildew (Pseudoperonospora cubensis), and brown spot (Corynespora cassiicola). A
      hyperspectral imaging system was es tablished to acquire and pre-process leaf
      images, as well as to extract leaf spectral properties. Owing to the complexity
      of the original spectral data, stepwise discriminate and canonical discriminate
      were executed to reduce the numerous spectral information, in order to decrease
      the amount of calculation and improve the accuracy. By the stepwise discriminate
      we selected 12 optimal wavelengths from the original 55 wavelengths, and after
      the canonical discriminate, the 55 wavelengths were reduced to 2 canonical
      variables. Then the discriminate models were developed to classify the leaf
      samples. The result shows that the stepwise discriminate model achieved
      classification accuracies of 100% and 94% for the training and testing sets,
      respectively. For the canonical model, the classification accuracies for the
      training and testing sets were both 100%. These results indicated that it is
      feasible to identify and classify cucumber diseases using hyperspectral imaging
      technology and discriminate analysis. The preliminary study, which was done in a
      closed room with restrictions to avoid interference of the field environment,
      showed that there is a potential to establish an online field application in
      cucumber disease detection based on visible spectroscopy.

PMID- 20672634
TI  - [Study on microstructure of J-aggregates of cyanine dyes].
AB  - In the present paper, the J-aggregate structures of three types of cyanine dyes
      adsorbed both on 0.4 microm AgBrI cubic crystal surface (100) and on 1.8 microm
      AgBrI tabular crystal surface (111) were studied by use of atomic force
      microscope (deltaFM). Several types of aggregation structures were observed for
      the three types of dyes on AgBrI crystals. Rectangular structure was formed on
      the crystal faces of (100) and (111) for both anionic and cationic cyanine dyes.
      On the surface of anionic-cationic cyanine dyes, however, herringbone stacking
      structure was formed, and a banded spectrum was correspondingly detected on the
      AgBrI crystal surface.

PMID- 20672635
TI  - [The application of chemical imaging to detection and enhancement of latent
      fingerprints].
AB  - Chemical imaging (CI) integrates conventional imaging and spectroscopy to attain
      both spectral and spatial components and structural information from an object
      simultaneously. Vibrational spectroscopic methods, such as infrared and Raman
      spectroscopy, combined with imaging are particularly useful. In recent years, CI
      has found important application in the field of forensic science due to its
      advantage of highly sensitive, rapid, non-destructive features and it can provide
      qualitative and quantitative information about specimen at one time. There are
      many methods for detection and enhancement of latent fingerprints. CI is an
      emerging platform technology with great potential to visualize latent
      fingerprints on many objects without any pre-treatment. CI can enhance the
      quality of the fingerprints developed by conventional methods, then form larger
      contrast with the background. With the advancement of instruments, the
      application of CI in the field of fingerprint detection will be more widely used.
      This paper provides an overview of the principal and classification of CI
      instrumentation, and reviews the application of CI to detection and enhancement
      of latent fingerprints. Finally, the direction of CI technology development is
      viewed.

PMID- 20672636
TI  - [Analysis of color gamut of LCD system based on LED backlight with area
      controlling technique].
AB  - Color gamut as a significant performance index for display system describes the
      color reproduction ability IN real scenes. Liquid crystal display (LCD) is the
      most popular technology in flat panel display. However, conventional cold cathode
      fluorescent lamp (CCFL) backlight of LCD can not behave high color gamut compared
      with cathode ray tube (CRT). The common used method of color gamut measuring for
      LCD system is introduced at the beginning. According to the inner structure and
      display principle of LCD system, there are three major factors deciding LCD's
      color gamut: spectral properties of backlight, transmittance properties of color
      filters and performance of liquid crystal panel. Instead of conventional
      backlight CCFL, RGB-LED backlight is used for improving color reproduction of LCD
      display system. Due to the imperfect match between RGB-LED' s spectra and color
      filter's transmittance, the color filter would reduce the color gamut of LCD
      system more or less. Therefore, LCD system based on LED backlight with area
      control technique is introduced which modifies backlight control signal according
      to the input signal After analyzing and calculating the spectra of LED backlight
      which passes through the color filters using method of colorimetry, the area
      sizes of color gamut triangles of RGB-LED backlight with area-control and RGB-LED
      backlight without area-control LCD systems are compared and the relationship
      between color gamut and varying contrast of liquid crystal panel is analyzed. It
      is indicated that LED backlight with area-control technique can avoid color
      saturation dropping and have little effects on the contrast variation of liquid
      crystal panel. In other words, LED backlight with area-control technique relaxes
      the requirements of both color filter performance and liquid crystal panel. Thus,
      it is of importance to improve the color gamut of the current LCD system with
      area-control LED backlight.

PMID- 20672637
TI  - [Study of vibrational spectra of humic substance in soils from the three Gorges
      Reservoir Area].
AB  - The six typical different parts of soils and sediments along the bank of the
      Three Gorges Reservoir Area (TGRA) were collected, and the humic substance
      isolated from the six parts of the soils and sediments' samples was separated to
      humic acid and fulvic acid, purified, and characterized with the combination of
      the Raman and IR vibrational spectroscopic technologies after cool-dried
      separation; through assigning the vibrational peaks in each part of the Raman and
      IR spectra of each sample part, the vibrational characteristics of the structures
      and the groups that belonged to the molecules of the humic acids and the fulvic
      acids in the soils and sediments of the TGRA were obtained; the changing features
      of the groups and structures in the humic acid and the fulvic aicd's molecules
      from the different soils and sediments in the TGRA were discussed with the
      environmental impact factors such as soil humic degree, the conditions of
      different soils conference, using and/or cultivating models and water level
      fluctuations. From the experimental results, the vibrations about C-O, C-C, and
      poly-hydrogen bonds dominate in the structures and the groups of each part' humic
      substance; the active vibration numbers in the upstream are more than in the
      downstream; the soil's humic degree has great effect on the formation of the
      humic substances' structures in soil's humic substance; the soil used as
      agricultural cultivating mode showed higher humic degrees in the upstream parts
      of the TGRA. The effect of the water level's fluctuation on the formation of the
      humic acid and fulvic aicd in the sediments of the TGRA is not obvious in the
      short time.

PMID- 20672638
TI  - [Theoretical studies on the structure, thermodynamics and spectral properties of
      rhodamine derivatives modified by amino of central ring].
AB  - The structures of three rhodamine derivatives were optimized by means of
      DFT/B3LYP method, and the data of the structural parameters and thermodynamic
      parameters of the excited state and ground state of the three rhodamine
      derivatives and their vibrational spectra and frontier molecular orbital energy
      level were obtained. On the basis of fully optimized structures of excited state
      and ground state, their gas absorption and emission spectra were studied by time
      dependent density functional theory (TD-DFT), while the effects of their
      structural features on thermal stability, frontier molecular orbital and spectra
      properties were fully analyzed. The results indicate that the compound a has the
      lowest reverse movement degree of terminal amino among these molecules, and in
      contrast, the compound b was better conjugated and planar, the reverse movement
      degree of terminal amino improved, the gas absorption and emission spectra were
      red shifted, and it has the longest maximum emission wavelength and the lowest
      thermal stability among these molecules. The compound c was best conjugated and
      planar, its thermal stability and energy of HOMO were the highest, its HOMO-LUMO
      gap was most narrow, and it has the longest maximum absorption wavelength. It was
      found that the reverse movement degree of terminal amino of compound c improved
      compared to b, so its maximum emission wavelength was blue shifted.

PMID- 20672639
TI  - [Antioxidant activity and spectroscopic behavior study with DNA of several Salen
      Mn(II), Eu(III) complexes].
AB  - Five kinds of Salen Mn(II) and two kinds of Eu(III) complexes were synthesized.
      Under the system of NBT/L-methionine, which creates and detects O2*-, the
      complexes of antioxidant activity were studied, and the conclusion revealed that
      all Mn(II) complexes have obvious antioxidant activity. The fluorescence study
      indicated that all the Salen metal complexes could bind with DNA, which shows
      their potential anticancer activity.

PMID- 20672640
TI  - [Analysis of the effects of pH and salt on the conformation of the sericin
      particles by DLS and TEM measurements].
AB  - The particles conformation of the sericin protein extracted from silkworm Bombyx
      mori was studied under the conditions of different pH and salt concentrations by
      infrared spectroscopy (IR), dynamic light scattering (DLS) and transmission
      electron microscopy (TEM) measurements. The IR spectrum of sericin protein arises
      predominantly from C=O stretching vibration around the amide I region of 1 700-1
      600 cm(-1). A strong trend of aggregation of the protein could be observed under
      specified experimental conditions. The apparent isoelectric point of the sericin
      protein was about 3.7. The DLS method was used to investigate the effects of pH
      and NaCl on the size distribution, where a large polydispersity of the system
      could be observed. Compared to pH 4 or high NaCl concentration, at pH 3, 8 or low
      NaCl concentration the sericin aggregation shows a relatively smaller size but
      larger polydispersity. TEM was used to investigate the microstructure of the
      aggregated sericin protein, where a loose and pine-like branched form could be
      observed at pH 3 or 8; however, a relatively compact structure was observed near
      pH 4 or at high salt concentration At pH 4 the spherical monomer size can be
      calculated at around (60 +/- 6) nm (n = 10) by TEM measurement. These phenomena
      could be explained by the effects of the electrostatic repulsion, hydrogen
      bonding and Van der Waals attractive force, which provide a basic theory for the
      application of sericin as biomaterial.

PMID- 20672641
TI  - [Determination of trace Au in mine sample by inductively coupled plasma atomic
      emission spectroscopy].
AB  - A method for the determination of trace gold by inductively coupled plasma atomic
      emission spectrometry (ICP-AES) in mine sample was proposed. The instrument
      parameters were optimized and the media of solution and interferences were
      studied systemically. The results showed that in less than 10% (phi) aqua regia
      medium, the acids had no influences on the determination, and after removing
      common cations in mineral samples by using 10% hydrochloric acid(phi), the
      residual matrix elements had no effect on the determination of Au with ICP-AES.
      The silicon in samples had serious spectral interference to Au 208. 2 nm, and the
      spectral interference was corrected with interference coefficient using the 251.6
      nm silicon line. With 10% HCl to remove the matrix and interference correction
      coefficient to eliminate the interference of silicon, trace gold in high-sulfur
      tailings samples was determined, the result was identical with the reference
      values by the method of enrichment with activated carbon-atomic absorption
      spectrometry. Under the experimental conditions, the detection limit for gold in
      mine sample was 0.10 g x t(-1).

PMID- 20672642
TI  - [Research on the content of trace elements and heavy metals in the three kinds of
      Zhejiang specific medicinal materials before and after processing].
AB  - By establishing the ICP-MS determining method, we determined the contents of Mn,
      Fe, Cu, Zn, Cr, As, Cd and Pb in the three kinds of Zhejiang specific medicinal
      materials before and after processing them. The recovery ratio with standard
      addition of the method is between 95.2% and 106.3, and the relative standard
      deviation between 0.69% and 2.34%. The results of the experiment show that the
      contents of useful metals Mn, Fe, Cu and Zn are fairly high both before and after
      processing, while the contents of harmful heavy metals Cd, Cr, Pb and As are all
      lower than the limited quantity in the standard of Chinese Pharmacopoeia. After
      processing, there seems to be some content changes in the trace elements and
      heavy metals. Different content changes depend on different processing methods.
      After processing, except the notable decrease in Pb, the contents of Cu, As and
      Cd are almost constant, while the contents of other elements are nearly all
      increased. The result seems to be related with the methods of processing. This
      experimental result provides us with new scientific foundation for the further
      research on the relationship between different processing methods and different
      efficacy of the three specific Zhejiang medicinal materials.

PMID- 20672643
TI  - [Analysis of the microfibrilla angles & crystallinity index of Daemonorops
      Margaritae with X-ray diffractometry and the effects of gamma-ray irradiation].
AB  - In order to find out the properties and improve the levels of high value-added
      processing and utilization of Chinese rattan resources, the Daemonorops
      Margaritae, a Chinese unique rattan, was chosen as the research material, then
      the microfibril angles (MFA) & crystallinity index (CrI) were measured through
      the X-ray diffraction method, and the effects of gamma-ray irradiation upon the
      MFA & CrI were analyzed. The results show that the MFA of the cane varied from
      33.4 degrees to 38.7 degrees with the average value of 36.1 degrees, and the MFA
      of the coretex were not larger than that of the core. The MFA were 36.2 and 35.8
      degrees, 35.9 and 35.4 degrees, and 36.2 and 35.4 degrees before and after
      irradiation with a radiation dose rate of 2.5 x 10(3) Gy x h(-1) and radiation
      dose of 3, 9 and 15 kGy, and decreased 1.10%, 1.39% and 2.21% respectively
      compared with the former. The CrI was in the range of 24.8%-32.0%, and the
      average CrI was 28.6%. The CrI of coretex was larger than that of the core. Under
      the same radiation conditions, the CrI was 28.1% and 26.0%, 28.1% and 26.9%, and
      28.5% and 27.1% before and after irradiation, and the latter decreased 7.58%,
      4.34% and 4.70% respectively compared to the former. With the radiation dose of 3
      kGy, the differences in CrI between with and without irradiation were most
      notable in the 0.001 level.

PMID- 20672644
TI  - [XPS analysis of beads formed by fuse breaking of electric copper wire].
AB  - The in-depth composition of beads formed by fuse breaking of the electric copper
      wire in different circumstances was studied by XPS with Ar+ ion sputtering. In
      addition, the measured Auger spectra and the calculated Auger parameters were
      compared for differentiation of the substances of Cu and Cu2O. Corresponding to
      the sputtering depth, the molten product on a bead induced directly by fuse
      breaking of the copper wire without cover may be distinguished as three portions:
      surface layer with a drastic decrease in carbon content; intermediate layer with
      a gentle change in oxygen content and gradually diminished carbon peak, and
      consisting of Cu2O; transition layer without Cu2O and with a rapid decrease in
      oxygen content. While the molten product on a bead formed by fuse breaking of the
      copper wire after its insulating cover had been burned out may be distinguished
      as two portions: surface layer with carbon content decreasing quickly; subsurface
      layer without Cu2O and with carbon and oxygen content decreasing gradually. Thus,
      it can be seen that there was an obvious interface between the layered surface
      product and the substrate for the first type of bead, while as to the second type
      of bead there was no interface. As a result, the presence of Cu2O and the
      quantitative results can be used to identify the molten product on a bead induced
      directly by fuse breaking of the copper wire without cover and the molten product
      on a bead formed by fuse breaking of the cupper wire after its insulating cover
      had been burned out, as a complementary technique for the judgments of fire
      cause.

PMID- 20672645
TI  - [Broad-area vertical cavity semiconductor optical amplifiers].
AB  - Based on the broad-area vertical cavity semiconductor optical amplifiers (VCSOA)
      of 970 nm, the amplifier gain and bandwidth characteristics were experimentally
      investigated and analyzed in the reflection mode. For 970 nm broad-area VCSOA
      operated in reflective mode, the maximum gain amplification of 24.8 dB and
      optical bandwidth of 0.14 nm (25 GHz) were reached when the injection current was
      57% of threshold current and the signal input power was 0.7 W. The experimental
      gain value was larger than the theoretical value, due to many modes existing in
      VCSOA. Each mode had relative gain amplification, so the experimental gain value
      was larger than the theoretical value. This kind of broad-area VCSOA was improved
      not only in optical gain but also in saturated input power. The authors optimized
      the structure design of the wide area VCSOA of 970 nm. The simulation results
      showed that the improvement of the gain and bandwidth of the semiconductor laser
      could be obtained by appropriately reducing the DBR reflectivity of the emitting
      laser on the vertical cavity surface.

PMID- 20672646
TI  - [Wide-range fiber spectral instrument covering].
AB  - To meet the requirements of outdoor field mineral analysis and remote sensing
      ground verification spectral analysis, the wide-range fiber spectral instrument
      covering 400 nm-2 500 nm was developed. The present article illustrates the
      design of the optical, mechanical and electrical parts of the instrument. The
      optical system utilizes grating horizontal-reflecting light route to implement
      the full coverage of the spectrum. Three line-array sensors are intercrossed in
      three directions on the spectrum surface to sense different spectrum ranges. CPLD
      device generates the sampling and driving temporal logic signals to the three
      line-array photoelectrical devices. Fourteen bits high speed AD converts the
      analog signals into digital ones. USB 2.0 is used for communication. The final
      results demonstrate that while implementing the measurement of wide spectrum, the
      instrument is improved in size, spectrum resolving power, signal quality and
      measuring speed. Ideal spectrum data were acquired.

PMID- 20672647
TI  - [Comparison of two types of Fourier transform imaging spectrometry].
AB  - The comparison between "large aperture static imaging spectrometry (LASIS)"
      designed by author and "method for simultaneously measuring the spectral
      intensity as a function of wavelength of all the pixels of a two dimensional
      scene" (MSMSI) designed by Israeli researchers is given. The difference of the
      interferometers and imaging systems in LASIS and MSMSI is discussed. The
      nonlinear curve of optical path difference of MSMSI is simulated. Inspired by the
      operation of MSMSI, the time modulated Fourier transform imaging spectrometry
      based on lateral shearing interferometer was presented. The optical path
      differences of different field of view were given under the condition of
      regularly rotating the lateral shearing interferometer.

PMID- 20672648
TI  - [Research on degradation of methylene blue by coal bottom ash-microwave
      irradiation method].
AB  - Coal bottom ash is rich in metals and transition metals, and with microwave
      irradiation these metals can effectively degradate organic matter. Methylene blue
      degradation by coal bottom ash-microwave irradiation mainly through hydroxyl
      radicals to degrade organic matter, and metals and rare metals in bottom ash can
      be used as a catalyst for deep oxidation of organic matter, can reduce processing
      costs, and reduce environmental pollution. In the present paper the main
      parameters including the amount of coal bottom ash, H2O2 dosage and time of
      microwave irradiation were investigated. The UV-visible spectra of methylene blue
      were determined. The results show that: under coal bottom ash and H2O2 microwave
      condition the degeneration rate of methylene blue was almost 100%. The dosage of
      coal ash can accelerate the reaction process, speeding up the degradation of
      methylene blue. The increase of H2O2 may provide more * OH and speed up the
      reaction process, but when up to a certain amount, the influence is weakened. The
      lengthening of microwave time may enhance the reaction temperature, and urge the
      methylene blue to degrade completely. For 0.125 g x L(-1) of methylene blue, by
      adding 1.0 g coal bottom ash, 5 mL H2O2 and under mesotherm microwave temperature
      for 4 min, the methylene blue can be all degradated.

PMID- 20672649
TI  - [Spectrum recovery methods for nonuniform sampling interferogram].
AB  - The interferogram acquired by imaging Fourier transform spectrometer (IFTS) can't
      be used directly and must be recovered. The spectrum recovery processes based on
      fast Fourier transform (FFT) is the traditional method which is used widely. For
      some IFTS, the nonuniform sampling of the interferogram is often occurrs. When
      the aliasing is neglected, the spectrum recovered by traditional method is often
      distorted. When the spectrum recovery processes based on Fourier transform are
      used, the precision of the recovered spectrum can be ensured, but the real-time
      processing requirement can't be satisfied. In order to acquire the precise
      recovered spectrum of the nonuniform sampled interferogram, the interpolation
      method and nonuniform fast Fourier transform (NUFFT) method were adopted. For the
      oversampled interferogram and partial undersampled interferogram, the spectrum
      recovery methods based on interpolation and NUFFT were presented respectively,
      and the applicability of these two methods is given. Finally, the computer
      simulation was performed, and the results indicate that NUFFT method is
      preferable to interpolation method not for undersampled interferogram but for
      oversampled interferogram.

PMID- 20672650
TI  - [Research on fiber methane sensing system based on prism gas cell].
AB  - A novel fiber methane detection system was constructed based on integration of
      prism gas cell and harmonic detection technique. The system can be applied to
      broad-range concentration detection. Grounded on the Beer-Lambert approximation,
      the detection of various concentration (0-20%) of methane was completed using
      subtraction of background and ratio processing method, as the atmosphere
      surroundings was treated as background. The direct absorption spectra for various
      concentration were measured using GRIN gas cell, combined with available DFB-LD,
      and the R5 line of the 2v3 band of methane was selected as absorption peak. The
      system was tested online during gas mixing process and the linear relation
      between system indication and concentration variation was validated, while the
      stability and dynamic response characteristics was confirmed by experiments. The
      system sensitivity can be adjusted according to the concentration level of
      various field environments by changing the prism distance using step motor. So
      that, the system can be applied to various application fields and can be adopted
      as a monitoring instrument for coalmine tunnel and natural gas pipeline.

PMID- 20672651
TI  - [Depressed sternum. Should it be treated?].

PMID- 20672652
TI  - [Cancer prevention and skin cancer screening. Become proactive!].

PMID- 20672653
TI  - [Communication with the patient should not fall by the wayside since: listening
      pays?].

PMID- 20672654
TI  - [The value of listening. 8 cases from long-term medical experiences].

PMID- 20672655
TI  - [Naturopathy consultation. Dementia].

PMID- 20672656
TI  - [Bee and wasp venom allergy. Equip your patients against anaphylaxis!].

PMID- 20672658
TI  - [Complementary medicine in cancer. Not a therapy without adverse effects].

PMID- 20672657
TI  - [Changes in the blood picture at the check up. Targeting with little laboratory
      work].

PMID- 20672659
TI  - [Infectious neurological diseases. Diagnostic confirmation from the cerebrospinal
      fluid].

PMID- 20672660
TI  - [Clinical aspects of neuroborreliosis].

PMID- 20672661
TI  - [Community acquired bacterial meningitis].

PMID- 20672662
TI  - [Modern diabetes management. DPP-4 inhibitors have been established as progress
      (interview by Christine Vetter)].

PMID- 20672663
TI  - [Dyspareunia].

PMID- 20672664
TI  - [The injured meniscus--which tests are predictive?].

PMID- 20672665
TI  - [Charcot foot in diabetes].

PMID- 20672666
TI  - [Osteoporosis management in general practice. Preventing spontaneous bone
      fractures].

PMID- 20672667
TI  - [The dumb boys].

PMID- 20672668
TI  - [Why Oma can become "peculiar" and still remain "Oma". Children's books on the
      topic of dementia].

PMID- 20672669
TI  - [Adolescents with neuromuscular diseases break away. Report of a "summer break"
      vacation leisure time club].

PMID- 20672670
TI  - [When dreams come true. The "make a wish" association delights young severely ill
      patients].

PMID- 20672671
TI  - ["Critical illness polyneuropathy" is also an illness in pediatric intensive care
      medicine].

PMID- 20672674
TI  - [Parental presence during resuscitation].

PMID- 20672672
TI  - [Boys are the dumb ones. The really disadvantaged sex].

PMID- 20672675
TI  - [Wrist watches in the hospital: are they really a risk factor for increased
      bacterial colonization of the hands? ].

PMID- 20672676
TI  - [Attention food service: a 10 minute walk is enough in winter for adequate
      vitamin D production].

PMID- 20672677
TI  - [Awareness through physical activity].

PMID- 20672678
TI  - [Study: there is a chronic lack of nurses in the hospital].

PMID- 20672679
TI  - [International congress on inclusion: pediatric and adolescent physicians want
      integrated schools for all children].

PMID- 20672680
TI  - [Fixed bed time makes children smarter. Better cognitive capacities with regular
      sleep].

PMID- 20672681
TI  - [Feminization of medicine... what about surgery?].

PMID- 20672682
TI  - [Current treatment strategies for sigmoid diverticulitis].
AB  - Treatment of colonic diverticular disease has evolved over the past years. Most
      episodes are simple and can be successfully treated with antibiotics alone. For
      complicated diverticulitis, a strong trend is developing towards less invasive
      therapies including interventional radiology and laparoscopic lavage in an effort
      to avoid the morbidity and discomfort of a diverting colostomy. Based on a better
      understanding of the natural history of the disease, the indication to
      prophylactic colectomy after a few episodes of simple diverticulitis has been
      seriously challenged. For those patients who need a colectomy, single port
      laparoscopy, NOTES and transanal specimen extraction are being proposed. However
      larger studies are needed to confirm the hypothetical advantages of these
      evolving techniques.

PMID- 20672683
TI  - [Oesophageal cancer: multidisciplinary approach].
AB  - Despite recent progresses, the prognosis of oesophageal cancer is still bad,
      mostly because of frequent late diagnosis. In early cases, radical surgery alone
      is able to cure 60-70% of the patients. In locally-advanced cases, on the other
      hand, surgical results are considerably worse and combined therapies are
      contemplated. In these cases, neoadjuvant therapy (induction chemotherapy
      followed by radiotherapy and surgical resection) is often proposed, but without
      formal proof of superiority. These combined therapies are heavy for the patient
      and complex for the team. They can only be decided and managed in the frame of
      intensive multidisciplinary collaboration. Future progresses will come at the
      same time from larger studies and from the efforts of the medical community
      towards earlier diagnosis of this disease.

PMID- 20672684
TI  - [Pain after inguinal hernia repair: what to do?].
AB  - Hernia repair one of the most frequently performed operations in general surgery.
      With the introduction of tension-free mesh repair, recurrence rates dropped well
      below 5% for open and laparoscopic procedures. However, chronic postoperative
      pain remains a widely neglected complication with a high socio-economic impact.
      It occurs in about 10-20% of patients after hernia repair. We review the
      different types of post-herniorrhaphy pain with the typical diagnostic features
      and we conclude with a pragmatic algorithm based on our clinical experience.

PMID- 20672685
TI  - [Patient's point of view on surgical innovations: for less traumatic surgery and
      enhanced recovery].
AB  - Surgical innovations (associating LESS, NOTES, robotics, images software and Fast
      track surgery) will allow a less and less invasive surgery. While these advances
      could be view as surgical or industrial marketing, or compared to the
      laparoscopic revolution, they simply answer patients' demand in a society
      changing its standard regarding: medical care, body image, recovery and
      rehabilitation. We will in this paper, according to results of a Google Survey
      analyzing population expectations of surgery, evaluate the interest of these
      surgical innovations. While, these innovations at least in part answers patients
      expectation, their therapeutic validity will have to be proved. It is our job, to
      foresee the future of surgery in accordance with health care system needs and
      patients expectation for adequate implementation of these innovations.

PMID- 20672686
TI  - [NOTES and single port access: surgical or marketing revolution?].
AB  - Promising new technologies are emerging in digestive surgery: Natural Orifice
      Transluminal Endoscopic Surgery (NOTES) and Single Port Access Surgery. They both
      aim to limit the surgical morbidity by decreasing the number of parietal
      accesses. The feasibility in human is obviously demonstrated, but numerous issues
      remain concerning the safety of these techniques. Furthermore, the expected
      advantages are not clearly demonstrated until now in the literature. In the
      future, it will be advisable to standardize techniques, in order to allow large
      clinical studies and to limit the potential complications of these approaches.

PMID- 20672687
TI  - [Outpatient surgery: an unstoppable evolution].
AB  - The trend is to definitely shorten hospital stays. It follows in the footsteps of
      a broader range of surgeries that can be managed in an ambulatory care setting.
      The expected benefits are: a reduction in costs, a shorter preoperative delay, a
      shorter absence for the work place and a lessened risk of hospital-borne
      infections. A multidisciplinary approach is essential for the success of such a
      program. Surgeons, anaesthetists and nursing staff must be prepared to modify and
      adapt their skills. The criterion of success for such an endeavour is a low level
      of readmissions and hospitalisations. If day surgery tends to keep the patient
      away for the hospital settings, it certainly places him in the centre of his
      medical management.

PMID- 20672688
TI  - [White skin marks].

PMID- 20672689
TI  - [A painful weaning].

PMID- 20672690
TI  - [Managed care: a solution to be applied with precautions].

PMID- 20672691
TI  - [Ah! The beautiful scam...].

PMID- 20672692
TI  - [Autism and media schizophrenia].

PMID- 20672693
TI  - [Tobacco schizophrenia: the French example (3)].

PMID- 20672695
TI  - [Networks: transparent utopia].

PMID- 20672694
TI  - [Abnormal because artificially fertilized?].

PMID- 20672696
TI  - [Anatomy, biology and concepts, pertaining to lung cancer stage classification].

PMID- 20672698
TI  - [Primary report of lobectomy with single utility port complete video-assisted
      thoracoscopic surgery].
AB  - BACKGROUND AND OBJECTIVE: Video-assisted thoracoscopic surgery (VATS) has been
      widely used in the diagnosis and treatment of chest diseases. The aim of this
      study was to explore the feasibility and clinical value of lobectomy with single
      utility port complete VATS. METHODS: From September 2009 to December 2009, 21
      cases underwent lobectomy with single utility port complete VATS. Of 21 patients,
      right upper lobectomy was 12 cases, left lower lobectomy 5 cases, right lower
      lobectomy 2 cases, left upper lobectomy 1 case, right middle lobectomy 1 case.
      RESULTS: The operation process were smooth in all patients and without conversion
      to thoracotomy. The mean operative time was (132.7 +/- 16.2) min and the mean
      intraoperative blood loss was (110.5 +/- 24.6) mL. The average chest tube
      drainage time was (3.1 +/- 1.3) d, and the mean hospitalization day was (5.2 +/-
      3.2) d. All patients recovered smoothly and without severe complications. There
      were no post-operative deaths. CONCLUSION: Lobectomy with single utility port
      VATS is technically feasible and has the advantages of minimal invasive and rapid
      recovery.

PMID- 20672697
TI  - [The International Association for the Study of Lung Cancer Staging Project.
      Prognostic factors and pathologic TNM stage in surgically managed non-small cell
      lung cancer].

PMID- 20672699
TI  - [Screening metastasis-associated genes from anoikis resistant A549 lung cancer
      cells by human genome array].
AB  - BACKGROUND AND OBJECTIVE: As a barrier to metastases, cells normally undergo
      apoptosis after they lose contact with their extra cellular matrix (ECM). This
      process has been termed "anoikis". Tumour cells that acquire malignant potential
      have developed mechanisms to resist anoikis and thereby survive after detachment
      from their primary site while traveling through the lymphatic and circulatory
      systems. This "anoikis resistance" is considered the first step to tumor
      metastases. The aim of this study was to screen metastasis-associated genes from
      anoikis resistant and adherent growth A549 lung cancer cell by Human Genome
      Array. METHODS: Establish anoikis resistant A549 lung cancer cell lines by using
      poly-hydroxyethyl methacrylate resin processed petri dishes, which causes cell
      free from adherent. The different expressed gene between anoikis resistant A549
      cell and adherent growth A549 cell was tested using human V2.0 whole-genome
      oligonucleotide microarray, a product of Capitalbio Corporation, Beijing. Screen
      metastasis-associated genes. RESULTS: 745 different expressed genes were
      screened, including 63 highly metastasis-associated genes. CONCLUSION: The
      successfully established anoikis resistant A549 cell lines and screened different
      expressed genes provide us basis for further research on metastasis of lung
      cancer.

PMID- 20672700
TI  - [Effect of dexamethasone on cisplatin induced apoptosis in primary cells from
      resected specimens with Chinese human lung adenocarcinoma ex vivo].

PMID- 20672702
TI  - [The role of GRP78 on the resistance to cisplatin in SPCA-1 cell line].
AB  - BACKGROUND AND OBJECTIVE: The expression levels of glucose-regulated protein 78
      (GRP78) were elevated and correlated with resistance to chemotherapy drug VP-16
      in lung cancer cells. However, little is known about the relationship between its
      expression and resistance to cisplatin in lung cancer cells. The aim of this
      study was to investigate the expression of GRP78 under the induction of A23187
      and its significance in the resistance to anti-tumor drugs cisplatin in a human
      lung cancer SPCA-1 cell line. METHODS: RT-PCR and Western blot were used to
      analyze the expression of GRP78 at mRNA and protein levels in SPCA-1 cell line
      induced byA23187 at different concentrations (0, 1, 2, 4, 6 microM). MTT was used
      to determine the effect of cisplation on cell survival. RESULTS: The expressions
      of GRP78 at both mRNA and protein levels were increased obviously in SPCA-1 cell
      line induced by A23187, with a manner of dose-dependent of A23187 to a great
      degree; MTT assay showed that the cell survival rate of the A23187-induced group
      decreased significantly compare to the control group, also with a concentration
      dependent manner of A23187. CONCLUSION: The expression of GRP78 at both mRNA and
      protein levels were increased obviously in SPCA-1 cell line induced by A23187.
      The enhancement of GRP78 showed a negative correlation with the cell survival
      rate treated by cisplatin. All these indicated that overexpression of GRP78 can
      enhance the sensitivity to cisplatin and there is correlation between the
      expression of GRP78 and resistance to cisplatin of human lung cancer SPCA-1 cell
      line.

PMID- 20672701
TI  - [Research of TGF-beta1 inducing lung adencarcinoma PC9 cells to mesenchymal cells
      transition].
AB  - BACKGROUND AND OBJECTIVE: It has been proven that epithelial-mesenchymal
      transition (EMT) not only correlated with embryonic development but also could
      promote tumor invasion and metastasis. Transforming growth factor beta-1 (TGF
      beta1) has been identified as the main inducer of tumor EMT. The aim of this
      study was to investigate the effects of TGF-beta1 on EMT and PI3K/AKT signaling
      pathway in lung adencarcinoma PC9 cells. METHODS: Cultured PC9 cells were treated
      with different concentrations of TGF-beta1 for 48 h. The morphological changes
      were observed under phase-contrast microscopy; EMT relative marker protein
      changes were assessed by Western blot and immunoflurescence staining. In
      addition, the expression of AKT and P-AKT were also measured by Western blot.
      RESULTS: The data showed that TGF-beta1 could induce PC9 morphological alteration
      from epithelial to mesenchymal and upregulate the expression of mesenchymal maker
      protein Fibronectin. Obviously, the expression of P-AKT was downregulated by TGF
      beta1 treatment for 48 h. CONCLUSION: TGF-beta1 might induce EMT of PC9 cells,
      accompanied by the changes of PI3K/AKT signaling pathway.

PMID- 20672703
TI  - [Establishment of orthotopic Lewis lung cancer model in mouse].
AB  - BACKGROUND AND OBJECTIVE: The mouse lung cancer orthotopic model includes
      spontaneous lung cancer model and endotracheal transplanted model, and etc. The
      spontaneous lung cancer needs longer time and does not ensure the rate of the
      generation of the tumor; as for endotracheal transplanted model, the position and
      size of the tumor are instable. In this study, the 3LL cell line was
      orthotopically transplanted into the lung of the C57BL/6 mice, compare to the
      heterotopic model, to discuss their stability and transfer-characteristics. And
      this study was also to optimize the method of establishing lung cancer orthotopic
      animal model. METHODS: Different quantity of 3LL cells were inoculated into the
      left oxter of C57BL/6 mice to establish the heterotopic model; or suspended with
      Matrigel then inoculated into the left lung of C57BL/6 mice to establish
      orthotopic model. The survival-time of the mice was examined. The tissue was
      collected for the subsequent histology assay after euthanizing the mice.
      Microvessels density (MVD) was observed and counted by immunohistological
      chemistry. CD44v was detected by flow cytometry. RESULTS: TTumor-form-rate of the
      heterotopic group were 100%, 66.7%, 16.7%, respectively, and had no macroscopic
      transfer. Tumor-form-rate of the orthotopic group were 100%, 100%, 83.3%,
      respectively, and had widespread transfer in contralateral chest and the lung.
      The median survival time of the orthotopic group (38, 35, 23 days) were less than
      the heterotopic group (82, 72, 50 days). MVD of the orthotopic group (120.2 +/-
      9.73) was higher than the heterotopic group (92.6 +/- 7.12). The expression of
      CD44v of orthotopic (26.46 +/- 1.56)% was higher than the heterotopic group
      (23.13 +/- 1.02)%. CONCLUSION: The lung cancer orthotopic model which established
      by 3LL cells transplanted into the lung of the mice is simple, dependable,
      repeatable and has stronger transfer characteristics than the heterotopic model.

PMID- 20672704
TI  - [Application of epidermal growth factor receptor tyrosine kinase inhibitor as the
      first-line therapy in patients with advanced non-small cell lung cancer].
AB  - BACKGROUND AND OBJECTIVE: Epidermal growth factor receptor tyrosine kinase
      inhibitor (EGFR-TKI) has been widely used as the second- and third-line therapy
      in patients with advanced non-small cell lung cancer (NSCLC). However, its effect
      in the first-line treatment is unclear. The aim of this study was to evaluate the
      efficacy and safety of EGFR-TKI as first-line therapy. METHODS: The clinical
      characteristics, responses rate, disease control rate and overall survival were
      retrospectively analyzed in 77 chemonaive patients with advanced NSCLC. All of
      the patients received oral gefitinib (250 mg/d) or erlotinib (150 mg/d) until
      disease progression or unacceptable toxicity occurrence. RESULTS: The overall
      response rate was 33.8% and the disease control rate was 68.8%. The median
      progression-free survival and the median survival time were 6.0 months and 8.9
      months, respectively. One-year survival rate was 61.4%. Responses correlated
      significantly with histology, PS score, smoking history, skin rash, EGFR
      mutations and serum CEA. Histology and skin rash were the independent predictors
      of survival. Common toxicities were skin rash and mild diarrhea. EGFR-TKI could
      improve the clinical symptoms and the quality of life. CONCLUSION: EGFR-TKI is
      effective and well tolerated as first-line therapy in patients with advanced
      NSCLC.

PMID- 20672705
TI  - Analysis of the effect of radiotherapy on malignant pleural mesothelioma when
      given on adjuvant or palliative basis.
AB  - BACKGROUND AND OBJECTIVE: This retrospective study was designed to evaluate the
      response and survival of malignant pleural mesothelioma to radiotherapy when
      delivered with surgery and chemotherapy and when delivered alone or with
      chemotherapy. METHODS: A study for 110 patients with malignant pleural
      mesothelioma who presented to radiotherapy department, National Cancer Institute,
      Cairo and received radiation therapy in the period fromJanuary 1999 to July 2007.
      RESULTS: Forty-six patients (41.8%) received trimodality therapy (surgery &
      adjuvant or neoadjuvant chemotherapy & adjuvant radiotherapy), while bimodality
      therapy (chemotherapy & radiotherapy) in 38 patients (34.5%), while 26 patients
      (23.6%) received single modality therapy (palliative radiotherapy), 22 patients
      (20%) developed local recurrence, 22 patients (20%) developed distant metastases
      months, 14 patients (12.7%) developed local disease progression, 25 patients
      (22.7%) are still alive and free of disease at time of reporting. The median
      survival for all patients was 16 months, while 12 and 18 months overall survival
      were 63.6% & 31.8% respectively while median survival for stage II, III, IV
      patients was 16.5, 12.5 and 8 months respectively. CONCLUSION: Multimodality
      approach involving surgery, chemotherapy and radiotherapy have been evaluated and
      proved its superiority in improving survival, especially in stages II.

PMID- 20672706
TI  - [TACE with Ar-He cryosurgery combined minimal invasive technique for the
      treatment of primary NSCLC in 139 cases].
AB  - BACKGROUND AND OBJECTIVE: TACE, Ar-He target cryosurgery and radioactive seeds
      implantation are the mainly micro-invasive methods in the treatment of lung
      cancer. This article summarizes the survival quality after treatment, the
      clinical efficiency and survival period, and analyzes the advantages and
      shortcomings of each methods so as to evaluate the clinical effect of non-small
      cell lung cancer with multiple minimally invasive treatment. METHODS: All the 139
      cases were non-small cell lung cancer patients confirmed by pathology and with
      follow up from July 2006 to July 2009 retrospectively, and all of them lost
      operative chance by comprehensive evaluation. Different combination of multiple
      minimally invasive treatments were selected according to the blood supply, size
      and location of the lesion. Among the 139 cases, 102 cases of primary and 37
      cases of metastasis to mediastinum, lung and chest wall, 71 cases of abundant
      blood supply used the combination of superselective target artery chemotherapy,
      Ar-He target cryoablation and radiochemotherapy with seeds implantation; 48 cases
      of poor blood supply use single Ar-He target cryoablation; 20 cases of poor blood
      supply use the combination of Ar-He target cryoablation and radiochemotheraoy
      with seeds implantation. And then the pre- and post-treatment KPS score, imaging
      data and the result of follow up were analyzed. RESULTS: The KPS score increased
      20.01 meanly after the treatment. Follow up 3 years, 44 cases of CR, 87 cases of
      PR, 3 cases of NC and 5 cases of PD, and the efficiencywas 94.2%. Ninety-nine
      cases of 1 year survival (71.2%), 43 cases of 2 years survival (30.2%), 4 cases
      with over 3 years survival and the median survival was 19 months. Average
      survival was (16 +/- 1.5) months. There was no severe complications, such as
      spinal cord injury, vessel and pericardial aspiration. CONCLUSION: Minimally
      invasive technique is a highly successful, micro-invasive and effective method
      with mild complications. To non-small cell lung cancer, we can improve the middle
      and long term clinical effect by using the different combination of multiple
      minimally invasive treatments according to the patient's condition.

PMID- 20672707
TI  - [Changes of exercise and the clinical effects among eldly non-small cell lung
      cancer survivors].
AB  - BACKGROUND AND OBJECTIVE: Exercise can improve circulation, muscular strength and
      happiness of cancer survivors. But more data were needed to demonstrate both the
      exercise ability of cancer suivivors after pulmonary lobectomy and the influences
      of exercise on their survivals. The aim of this study was to examine changes of
      exercise and its clinical effects among eldly non-small cell lung cancer
      survivors. METHODS: Elderly non-small cell lung cancer survivors who had
      progression-free disease after surgery, chemotherapy, radiation therapy or
      tyrosine kinase inhibitors were included. Their exercises and participation rates
      per week before cancer diagnosis, after 3 months anticancer therapy and 1 year
      after diagnosis as well as their exercise motivations and prevalences were
      investigated retrospectively. RESULTS: Forty-eight elderly non-small cell lung
      cancer survivors were selected. Moderate-vigorous intensity exercise had by the
      elderly progressin-free non-small cell lung cancer survivors after diagnosis
      decreased, but the participation rate of light intensity exercise was higher in 1
      year after diagnosis than before diagnosis. 75.9% (14/58) patients had exercise
      up to the standard and the cancer recurrence rate was 20.0% (7/35). The
      recurrence rate of the other group was 35.7% (5/14), and the risk ratio of
      recurrence was 2.14 (95% CI: 0.81-5.68, P = 0.26). The most common motivations of
      exercise were improving health, increasing physical activity, maintaining healthy
      life style and improving immunity. And the main disturbances were fatigue,
      discomfort and lack of motivation. CONCLUSION: The exercise participation rate
      during anticancer treatment among the elderly non-small cell lung cancer
      survivors decreased and did not return to prediagnosis levels after treatments
      were completed. The relationship between exercise and recurrence of cancer was
      not clear and needed further work.

PMID- 20672708
TI  - [mTOR and non-small cell lung cancer].

PMID- 20672709
TI  - [Advances of ectopic ACTH syndrome complicated by lung cancer].

PMID- 20672710
TI  - [Advances in microwave coagulation therapy of lung cancer].

PMID- 20672711
TI  - Lymphomatoid granulomatosis with splenomegaly and pancytopenia.
AB  - Lymphomatoid granulomatosis (LG) is an angiocentric lymphoproliferative disease.
      It usually involves lung, skin, and central nervous system, but splenomegaly and
      pancytopenia are the rare manifestations of the disease. We report a 15-year-old
      boy presented with fever, dry cough and dyspnea from two months ago, after
      admission patient had nodular lesions on the left leg and hepatosplenomegaly.
      Then he manifested neurologic signs such as seizure, aphasia and right-sided
      hemiplegia. Chest X-ray and CT scan revealed bilateral pulmonary nodules
      predominantly in lower lobes and peripheral lung fields. Laboratory exams showed
      pancytopenia. Skin biopsy was done, and histopathological examination and
      immunohistochemistry evaluation confirmed lymphomatoid granulomatosis. He was
      treated with steroid and cyclophosphamide but succumbed by neurologic
      involvement.

PMID- 20672713
TI  - [Fighting pain].

PMID- 20672712
TI  - [A case report of congenital bronchobiliary fistula in adults].

PMID- 20672714
TI  - [Nursing basics in anesthesia: material to carry out regional anesthesia
      technics].
AB  - Nursing career tend to specialize more each time in the different specialties,
      for this reason the introduction of the specialist nurse in anaesthesia required
      a specific knowledge on this medical discipline. The evolution of technologies
      applied to the design of new needles, echography machines and other equipment for
      regional anaesthesia techniques make essential to update of our knowledge in this
      area. This piece of work pretend to show the readers (nurses working in
      anaesthesia and others practitioners involved in surgical areas or pain
      management) a current view about the material and other instruments, mostly used
      in the different types of nerve blocks in regional anaesthesia. The aim of this,
      is provided an easy introduction of the regional anaesthesia to the junior
      practitioners, and updated evidence to the senior practitioner. The work is
      structured in a classic way: introduction, central blocks (subarachnoid and
      epidural), peripheral blocks, regional intravenous anaesthesia, eye block,
      asepsis and conclusions.

PMID- 20672715
TI  - [Less pain during puncture by a peripheral venous catheter; a bibliographical
      review on adults].
AB  - Canalizing veins is a habitual technique carried out by nurses. Inserting a
      catheter in a peripheral vein causes pain. The importance of fine quality in
      nursing treatment implicitly bears on a person's well-being. In daily practice,
      health professionals do not use any method to reduce pain when inserting a
      catheter. The authors observations led them to believe in the need to carry out a
      bibliographical review whose objective was to discover all the methods used to
      reduce pain caused by puncturing a peripheral vein. Six randomly assigned
      clinical tests and a meta-analysis evaluate the effectiveness of: The use of
      Valsalva, an analgesic cream which contains two local amino-amide anesthetics;
      lidocaine and prylocaine (EMLA) compared to another analgesic cream, Myolaxin; a
      meta-analysis of twenty studies evaluates the degree by which pain is diminished
      by one such method: an EMLA cream; an anti-inflammatory skin dressing
      (diclofenaco), a diclofenaco dressing versus an EMLA anesthetic dressing, 0.25 ml
      subcutaneous injection of 1% mepivaina, an amida type local anesthetic; and
      direct photography moments before puncture occurs to use the effects of a flash
      of light. All these methods studied proved effective in reducing pain. Creams and
      dressing prove to be unaggressive methods but require some time for application
      prior to puncture. Using a camera flash, subcutaneous injection of mepivacaine
      and the application of Valsalva can be effective alternatives to reduce pain when
      puncturing veins in patients who require emergency care.

PMID- 20672716
TI  - [Pain and suffering; commentaries by patients who undergo kidney dialysis].
AB  - Pain and suffering are two frequent symptoms in patients who undergo kidney
      dialysis, which directly affects their quality of life. This present study
      analyses, by means of a qualitative methodology the pain and suffering registered
      in commentaries by kidney patients to determine what they refer to when they
      speak about pain and suffering and to be able to offer health professionals some
      elements for making judgments which favor more individualized treatment. Patients
      who undergo dialysis refer to two clearly distinct types of pain: endogenous, or
      pain caused by secondary effects their disease has, and exogenous, or anxiety or
      the loss of something, in this instance their health status, which accompanies
      their suffering. When confronting such a situation, a health professional must
      find resources which permit him/her to provide a clear and concise response to
      these two symptoms in the daily life of kidney patients, using innovating tools
      which are removed from a simple pill or syrup.

PMID- 20672717
TI  - [Laughter therapy for chronic skeletal muscular pain].
AB  - The authors explain the effects introducing workshops for laughter therapy and
      relaxation to a unit dedicated to therapeutic education and functional
      rehabilitation; the authors test to see if the application of this therapy helps
      to decrease pain, to improve mobility and to reduce an altered emotional state,
      such as anxiety-depression, common among chronic pain patients.

PMID- 20672719
TI  - [Personalized patient care for the postoperative acute pain: experience in a
      local hospital].
AB  - Acute Pain Units aim to apply effective methods for analgesic control, providing
      an organised and systematic health care adapted to each patient. The Acute Pain
      Unit Staff Nurse will put into effect high quality nursing care to the surgical
      patient through an interprofessional approach in the personalization, seamless
      care and postoperative acute pain treatment.

PMID- 20672718
TI  - [Thromboembolic prophylaxis in bariatric surgery. A multidisciplinary protocol].
AB  - Severe or morbid obesity is one of the 21st century epidemics. Surgery is the
      most important and cost-effective treatment. Bariatric procedures are becoming
      very common in our Hospitals. Thromboembolic events such us deep venous
      thrombosis or pulmonary embolism (PE) are the most common medical cause of death
      after these procedures. Incidence of PE may arise to 3% after surgery and its
      mortality is about 75%. Prophylactic protocols have not been clearly defined
      until now. These protocols have to consider special patients, such as morbid
      obese ones; different kind of procedures, most of the laparoscopic; and patients'
      comorbidities. By the other hand, treatment for morbid obesity has to be
      considered by a multidisciplinary approach. Here we present the protocol that has
      been initiated at our Institution. After a long and high experience in bariatric
      procedures, we have defined a multidisciplinary protocol to prevent
      thromboembolic events after surgery where nurses and surgeons play a leading
      role. The combination of physical, pharmaceutical and educational measures all
      together are the key for the adequate prevention in these patients.

PMID- 20672720
TI  - [Medical approach of pain in prehospitalary system].
AB  - In emergency medical system (EMS), the analgesia is one of the principal
      treatment after rule at risk of death for the patient. This article describes
      some types of pain according to presentation and their treatment in the
      prehospitalary ambit.

PMID- 20672721
TI  - Comparison of at-home and in-office tooth whitening using a novel shade guide.
AB  - OBJECTIVE: This study evaluated the time necessary for at-home whitening (HW) to
      match the results of an in-office (OW) treatment, side effects and patients'
      preferences/perceptions. METHODS: The tooth color change of 20 subjects was
      measured using a shade guide (BSG) and spectrophotometer (ES). Color difference
      was calculated: delta E* = [(delta L*)2 + (delta a*ab)2 + (delta b*ab)2]1/2. The
      whitening treatments were randomly applied to the right or left maxillary
      anterior teeth, in-office, with 25% hydrogen peroxide or at-home, overnight, with
      10% carbamide peroxide. The tooth color was evaluated at baseline, one day after
      OW, six days (five days after HW) and at 20 days (14 days after HW and 19 days
      OW). Subjects rated their tooth and soft tissue sensitivity (1-10 scale). The
      results were analyzed by two-way RM ANOVA/Tukey's and Mann-Whitney (p<0.05).
      RESULTS: At six days, the teeth that were treated with HW and OW presented delta
      E* = 5.2 and 6.6, respectively, delta BSG = 3, and at 20 days, they presented
      delta E* = 6.2 and 6.6, respectively, delta BSG = 3. Less than 40% of the
      subjects experienced tooth sensitivity after OW and HW. No subjects experienced
      tooth and gingival sensitivity at 20 days. Seventy-four percent preferred HW over
      OW, 63% recommended OW and 100% recommended HW. CONCLUSION: While there was a
      subtle difference in delta E* between HW and OW at six days, the measurement of
      delta E* and delta BSG agreed that five days of home whitening produced the same
      results as a single in-office treatment. The tissue and teeth sensitivity were
      mild and transient. Subjects preferred and would recommend HW over OW.

PMID- 20672723
TI  - Clinical evaluation of resin-based composites in posterior restorations: two-year
      results.
AB  - OBJECTIVE: This study evaluated the clinical performance of a nanohybrid and a
      low shrinkage posterior composite in Class I and II restorations after two years.
      METHODS AND MATERIALS: A total of 82 Class I and Class II cavities were restored
      in 31 patients (10 male, 21 female) by one clinician using Grandio and Quixfil
      and the manufacturers' self-etch adhesives (Futura Bond and Xeno III) according
      to the manufacturers' instructions. Two previously calibrated operators
      clinically evaluated the restorations one week after placement (baseline) and six
      months, one year and two years after placement using modified USPHS criteria.
      Statistical analysis was completed using the Pearson Chi-square and Fisher's
      Exact Test (p<0.05). RESULTS: All patients attended the 12-month recall and no
      lack of retention was observed. With respect to color match, marginal adaptation,
      secondary caries and surface texture, no significant differences have been found
      between the two restorative materials that were tested after 12 months (p>0.05).
      None of the restorations had shown any marginal discoloration and anatomic form
      loss until the end of the 12-month period. Two-year recall data demonstrated an
      83.87% recall rate (26 patients). Grandio restorations showed a significant
      deterioration of the surface properties that demonstrated 26% Bravo scores, which
      are still clinically acceptable. None of the restorations exhibited postoperative
      sensitivity at any evaluation period. CONCLUSIONS: It was concluded that nanofill
      (Grandio) and posterior composite (Quixfil) demonstrated acceptable clinical
      performance after two years. However, further evaluations are necessary for the
      long-term clinical performance of these materials.

PMID- 20672722
TI  - Concordance between preoperative and postoperative assessments of primary caries
      lesion depth: results from the Dental PBRN.
AB  - This study investigated the concordance between pre- and postoperative
      assessments of primary caries lesion depths by dentists from The Dental Practice
      Based Research Network (DPBRN; www.DentalPBRN.org). A total of 229 DPBRN dentists
      collected data on 8,351 consecutive restorations inserted due to primary caries
      in 5,810 patients. Dentists estimated the preoperative depth of caries lesions
      based on the diagnostic methods they typically used. The preoperative depth was
      then compared to the postoperative depth, which dentists determined using actual
      clinical observation. Both estimated and observed depths were recorded as being
      in the outer half (E1) or inner half (E2) of enamel, or in the outer third (D1),
      middle third (D2) or inner third (D3) of dentin. Most restorations were placed to
      treat lesions that were preoperatively assessed as extending to the D1 (53%) and
      D2 (25%) depths. Of the restored caries lesions, 10% were preoperatively assessed
      as being limited to E2 depth and 3% to E1 depth. The majority of the restored
      enamel lesions were located on occlusal surfaces. Preoperative estimates of
      caries lesion depth were more concordant with postoperative depths when the
      lesion was at an advanced stage: 88% concordance at the D3 depth, compared to 54%
      concordance at the E1 depth. DPBRN dentists can discriminate caries lesions at
      different depths, but the accuracy of their depth assessments was higher for
      dentin than for enamel lesions. In general, DPBRN dentists were more likely to
      underestimate than overestimate the depth of caries lesions, and the extent of
      underestimation was greater for enamel than for dentin lesions.

PMID- 20672724
TI  - Effects of bleaching agents on human enamel light reflectance.
AB  - OBJECTIVES: Tooth whitening has been associated with splitting-up chromogenic
      molecules by hydrogen peroxides. Though micromorphological alterations are well
      documented, little is known about optical changes as a function of shifting in
      wavelengths. Therefore, the aim of the current study was to measure reflectance
      changes after bleaching in vitro by using a spectrometer. METHODS: Forty-eight
      enamel slabs (diameter = 5 mm) were prepared from the sound enamel of extracted
      human teeth that were: 1) fully impacted, 2) from juveniles ages 10 to 16 years,
      3) from adults 35 to 45 years of age and 4) from seniors older than age 65. In
      all specimens, the baseline total reflectance measurement was performed with a
      computer-assisted spectrometer (Ocean Optics, Dunedin, FL, USA) within
      wavelengths (wl) from 430 nm to 800 nm. Four enamel samples of each age group
      were exposed to either 10% or 15% carbamide peroxide (Illumine Home, Dentsply,
      Konstanz, Germany) or 35% hydrogen peroxide (Pola Office, SDI Limited, Victoria,
      Australia). After surface treatment, all slabs underwent total reflectance
      measurement again. Statistical analysis was calculated at wl 450, 500 and 750 nm
      using the Student's paired t-test and one-way variance analysis. RESULTS: Total
      reflectance significantly increased after bleaching at all enamel maturation
      stages, irrespective of the bleaching agent concentration, for wl 450 nm (blue)
      and 500 nm (green) with p<0.0001. At 750 nm (red), significant changes only
      occurred in enamel from adults and seniors (p<0.04). However, the efficacy of
      bleaching was significantly increased in the blue and green light spectra as
      compared to the red spectra (p<0.0001). CONCLUSIONS: The results of the current
      study showed that the exclusive assumption of the "chromophore effect" in dental
      bleaching could not be sustained, because whitening of the dental enamel works at
      different maturation stages, even in impacted teeth. This effect is irrespective
      of the bleaching protocol used and the bleaching agent concentration.

PMID- 20672725
TI  - Investigation of mechanical properties of modern dental composites after
      artificial aging for one year.
AB  - This in vitro study investigated the aging behavior of dental composites with
      regard to surface roughness (SR), Vickers hardness (VH) and flexural strength
      (FS), and the study elucidated the impact of artificial aging parameters. One
      hundred and sixty-five rectangular specimens were prepared from five composites
      (Filtek Supreme XT, Filtek Silorane, CeramX, Quixfil, experimental ormocer) and
      subjected to various artificial aging protocols (storage in distilled
      water/ethanol/artificial saliva for 7, 90 and 365 days; thermal cycling, 2 x 3000
      cycles 5/55 degrees C). SR, VH and FS were determined at baseline and after each
      aging treatment. Means and standard deviations were calculated; statistical
      analysis was performed using three-way ANOVA and the Tukey-Kramer multiple
      comparison test (alpha=.05). The results showed a significant influence in the
      composite and aging duration on mechanical parameters; the aging medium did not
      have a significant influence on VH and FS, but there was a significant influence
      on SR. The highest overall VH was found for theexperimental ormocer; Filtek
      Silorane yielded the lowest values. For FS, the significantly highest values were
      found for Filtek Silorane, and the lowest values were found for the experimental
      ormocer. Prolonged aging periods (90 or 365 days) or thermal cycling led to
      significant decreases in both VH and FS and significant increases in SR. The
      findings of the current study indicate that composites differ significantly for
      SR and its mechanical properties with regard to FS and VH, as well as in aging
      behavior. Generally, artificial aging leads to a significant decrease in
      mechanical properties, which underlines the relevance of continuous improvement
      of dental composites.

PMID- 20672726
TI  - Surface/interface morphology and bond strength to glass ceramic etched for
      different periods.
AB  - This study evaluated the influence of etching periods on the surface/interface
      morphology and bond strength to glass ceramic with or without application of an
      unfilled resin after silane. Ceramic discs were divided into 12 groups, defined
      by etching time with 10% hydrofluoric acid: G1/G7--etching for 10 seconds, G2/G8-
      20 seconds; G3/G9--40 seconds; G4/G10--60 seconds; G5/G11--120 seconds and G6/G12
      -60 + 60 seconds. All the groups were silanated after etching and G7 - G12
      received a layer of unfilled resin after silane. Microshear testing using resin
      cement was performed, with 12 resin cylinders tested per group. The data was
      submitted to two-way ANOVA and the Student-Newman-Keuls' test (p<0.05).
      Evaluation of the etching pattern and bonding interfaces was conducted by SEM.
      The bond strength means (MPa) were: 19.4 +/- 3.5, 22.3 +/- 5.1, 22.2 +/- 3.2,
      17.8 +/- 2.1, 15.3 +/- 3.0 and 14.3 +/- 1.8 for G1-G6 and 17.4 +/- 4.8, 21.3 +/-
      2.1, 21.1 +/- 2.3, 24.7 +/- 5.8, 20.4 +/- 2.2 and 18.5 +/- 4.6 for G7-G12. Poor
      etching was detected after 10 seconds of conditioning; whereas deep channels were
      extensively observed on surfaces etched for 120 and 60 + 60 seconds. Unfilled
      voids underlying the ceramic-cement interface were detected when only silane was
      applied. Full completion of the irregularities on G11 was detected using unfilled
      resin. When only silane was applied, the 60-second group and those etched for
      longer periods showed lower bond strengths. When both silane and unfilled resin
      were applied, all etching periods generally showed similar values. In conclusion,
      the etching period influenced the surface/interface topography and bond strength
      to ceramic. The application of unfilled resin was able to infiltrate all unfilled
      voids beneath the ceramic-cement interface, except on re-etched surfaces.

PMID- 20672727
TI  - Effect of mode of application on the microtensile bond strength of a self-etch
      and etch-and-rinse adhesive system.
AB  - This study examined the 24-hour microtensile bond strength (microTBS) of a three
      step etch-and-rinse (All Bond 3 [AB3]) and a two-step self-etch system (All Bond
      Self-Etch [ABSE]) to dentin and ground enamel, varying the application mode.
      METHODS: AB3 was applied according to the following procedures: A-phosphoric acid
      + adhesive application. The adhesive was then light-cured before resin buildup. B
      similar to Procedure A, except that a thin layer of bonding resin was applied
      over the cured adhesive; C-similar to Procedure B, however, the adhesive was not
      light-cured before application of the bonding resin. ABSE was applied according
      to the following procedures: A--the acidic adhesive was applied and light-cured;
      B--after the acidic adhesive application and light-curing, a thin layer of ABSE
      Liner was applied and light cured; C--similar to B, however, the acidic adhesive
      was not light cured before application of the ABSE Liner. Resin composite
      buildups (Charisma) were bonded to teeth substrates after adhesive application.
      The bonded specimens were sectioned into beams 0.9 mm2 after storage in water (24
      hours/37 degrees C) and subjected to microTBS with a crosshead speed of 0.5
      mm/minute. The average values (MPa) obtained in each substrate were subjected to
      two-way repeated measures ANOVA and the Tukey's test (alpha=0.05). RESULTS: No
      significant difference was observed among the experimental groups either in
      ground enamel or dentin. CONCLUSIONS: The 24-hour microtensile bond strength of
      All Bond 3 and All Bond Self-Etch was similar, regardless the mode of application
      of the adhesive systems.

PMID- 20672728
TI  - Comparative radiopacity of six flowable resin composites.
AB  - OBJECTIVE: This study investigated the radiopacity of six commercially available
      flowable composites by using a digital image analysis method to determine the
      mean gray values of the materials. METHODS: The flowable resin composites
      evaluated in this study were Clearfil Majesty Flow, Estelite Flow Q, Tetric N
      Flow, Esthet X Flow, Filtek Supreme XT Flow and Gradia Direct LoFlo. Ten sample
      discs (6 x 1 mm) for each group were prepared and 1-mm thick slices were obtained
      from freshly-extracted teeth for the control group. The mean gray values (MGVs)
      of each specimen and aluminum (Al) stepwedge were measured by using the histogram
      function of a computer graphics program. Analysis of variance (ANOVA) was used to
      investigate the significance of the differences among the groups. For pairwise
      comparisons, the Tukey test was applied (alpha=0.05). RESULTS: The radiopacity
      values of Gradia Direct LoFlo, dentin and Estelite Flow Q were close to that of 1
      mm Al. Tetric N Flow and Cl Majesty Flow were more radiopaque than enamel,
      whereas Filtek Supreme XT Flow had a similar radiopacity to enamel. CONCLUSION:
      The radiopacity of flowable composites varies considerably, and care must be
      taken when selecting an appropriate material to enable secondary caries detection
      under posterior composite restorations.

PMID- 20672729
TI  - The influence of elastic modulus of base material on the marginal adaptation of
      direct composite restoration.
AB  - This study compared the marginal adaptation of direct composites under base
      materials with different elastic moduli. MOD cavities were prepared in 30 teeth.
      The cervical margin was placed 1 mm above the cementoenamel junction (CEJ) in one
      side and 1 mm below the CEJ in dentin in the other. The teeth were randomly
      divided into the following six groups (five teeth each) according to the base
      materials used: No base (Group 1), experimental flowable composite (Group 2),
      Helioflow (Ivoclar Vivadent) (Group 3), Tetric Flow (Group 4), Heliomolar HB
      (Ivoclar Vivadent) (Group 5) and Fuji II LC (Group 6). In Group 1, after etching
      the cavity enamel with 35% phosphoric acid, the cavities were primed and bonded
      with AdheSE, then filled with Tetric Ceram according to the manufacturer's
      instructions. In the other groups, after placing the base materials (1 mm thick)
      into the cavity, the cavity was filled with Tetric Ceram using the same methods
      as in Group 1. After storing the specimens in distilled water for seven days,
      they were finished and polished. Using stereomicroscopy at 150x magnification,
      marginal adaptation of the specimens was determined and the percentage of the
      imperfect margin (IM%) in the pre-loaded specimens was calculated. A mechanical
      load was applied using a custom-made Chewing simulator. All specimens were
      submitted to 600,000 load cycles at 49N with a frequency of 2Hz. The IM% in the
      post-load specimens was calculated. Repeated measured one-way ANOVA with Tukey
      was applied to compare the IM% in the six groups at the 95% confidence level. The
      results of statistical analysis indicated that the IM% was Group 3, 4, 6 < or = 2
      < or = 5 < or = 1.

PMID- 20672730
TI  - Antibacterial activity of various self-etching adhesive systems against oral
      streptococci.
AB  - The antibacterial properties of self-etching adhesive systems constitute an
      important issue in operative dentistry, since viable bacteria can still be
      present after cavity preparation. The current study evaluated the antibacterial
      activity of five one-step self-etching adhesives (SEAs) and four self-etching
      primers (SEPs) against oral streptococci. Clearfil S3 (S3), One-Up Bond F Plus
      (OU), Futurabond NR (FB), GBond (GB), Xeno IV (X4), Clearfil SE Bond (SE),
      Clearfil Protect Bond (PB), Adper SE Plus (AS) and AdheSE (AD) were tested for
      antibacterial activity against five streptococci species: S oralis, S sanguinis,
      S cricetus, S mutans and S sobrinus. Chlorhexidine (0.12%) and phosphoric acid
      (37%) gel were used as control. The agar diffusion test method was used. Plates
      containing BHI agar and 300 uL of bacterial cell suspension (0.5 MacFarland) were
      prepared. Holes 6 mm in diameter were made and partially filled with
      bacteriological agar. Then, 10 uL of each SEA or SEP was dropped and the plates
      were incubated under microaerophilic atmosphere at 37 degrees C for 48 hours and
      the diameter of each halo was registered. The results were analyzed by two-way
      ANOVA and Tukey test. PB exhibited the most effective antibacterial activity
      against oral streptococci. The performances of SE and FB were similar or better
      than chlorhexidine for all bacteria. S3, X4, AS, AD, OU and GB showed
      significantly lower inhibition values. Among the species tested, S oralis was the
      most sensitive to all self-etching adhesive systems; on the other hand, S
      cricetus, S mutans and S sobrinus were more resistant. Among the self-etching
      adhesive systems evaluated, Clearfil Protect Bond exhibited the most effective
      antibacterial activity against oral streptococci.

PMID- 20672731
TI  - The influence of matrix type on the proximal contact in Class II resin composite
      restorations.
AB  - PURPOSE: This in vitro study evaluated the efficiency of various types of
      matrices in reconstructing the proximal contact area in Class II resin composite
      restorations. MATERIALS AND METHODS: Standardized MO cavities were prepared on
      artificial molars of a manikin model. Resin composite (Spectrum TPH-3)
      restorations were placed using the following matrices (n=10): a) circumferential
      straight metal matrix with Tofflemire retainer-A, b) circumferential pre
      contoured metal matrix system-B (Adapt SuperCap), c) circumferential pre
      contoured transparent matrix system-C (Adapt SuperCap) and d) sectional pre
      contoured metal matrix system-D (Palodent). After completion of each restoration,
      the manikin model was fixed on a tension-meter apparatus and an orthodontic wire
      was used to assess the contact tightness (CT), length of contact arc (LCA) and
      position of contact point relative to LCA% (PCP). The same measurements were
      performed on a group of intact molars (REF). The results were statistically
      analyzed with one-way ANOVA and the Tukey test, as well as the unpaired t-test
      (alpha=0.05). RESULTS: Matrix D provided the highest CT with the highest LCA,
      which presented a statistical difference relative to the intact tooth.
      Restorations with matrix B provided higher LCA than those with matrices A and C,
      which were found to be comparable to that of an intact tooth. The contact points
      (PCP) of the filled teeth were located more cervically in matrix D relative to
      the intact tooth (lower PCP), whereas matrices A, B and C showed more occlusal
      location (higher PCP). CONCLUSIONS: Differences were noted among all the matrices
      evaluated and none was proven sufficient to reconstruct the proximal contact
      characteristics of an intact tooth.

PMID- 20672732
TI  - Effect of carbamide peroxide bleaching gel concentration on the bond strength of
      dental substrates and resin composite.
AB  - PURPOSE: This study evaluated the effect of bleaching gel containing 10%, 15% and
      20% carbamide peroxide (CP) on the bond strength of dental enamel or dentin and
      resin composite restorations. METHODS: The buccal surfaces of 12 bovine tooth
      crowns were conditioned with 37% phosphoric acid, and the adhesive resin Single
      Bond 2 and the resin composite Filtek Z350 were used to perform the restorations.
      The blocks were sectioned to obtain bar specimens. Each specimen group (enamel-E,
      dentin-D) was divided into four subgroups (n=15): S-artificial saliva; 10-10% CP
      bleaching; 15-15% CP bleaching; 20-20% CP bleaching. CP was applied for six hours
      daily for two weeks. The specimens were submitted to the sigma test in a
      universal testing machine. The data were analyzed by one-way ANOVA and the Tukey
      post-hoc test and a correlation analysis (r) was performed. RESULTS: For Group E,
      the mean value (+/- standard-deviation) was 21.86 (+/- 6.03)a, 18.91 (+/-
      8.31)ab, 15.43 (+/- 7.44)b and 10.6 (+/- 4.94)c for ES, E10, E15 and E20,
      respectively. For Group D, the a values were 34.73 (+/- 4.68)a, 35.12 (+/-
      13.43)a, 29.67 (+/- 6.84)ab and 24.56 (+/- 6.54)b for DS, D10, D15 and D20,
      respectively. A negative correlation between the CP concentration and mean values
      was observed for both the enamel (r=-0.95) and dentin (r=-0.85) groups.
      CONCLUSION: In the current study, the bond strength of the restoration to enamel
      and the restoration to dentin were influenced by the application of CP and was
      dependent on the CP concentration in the bleaching gel.

PMID- 20672734
TI  - Stepwise excavation in a permanent molar: 17-year follow-up.
AB  - The current study presents a 17-year clinical report of stepwise excavation and
      indirect pulp capping in a lower right first molar, with great dentin destruction
      and a lack of dentin support of the cusps. At the first appointment, indirect
      pulp capping with calcium hydroxide and a temporary filling with zinc oxide
      cement were performed to minimize the risk of pulp exposure during excavation.
      After 45 days, the remaining carious tissue was removed and a restoration with
      glass-ionomer lining (Vitrebond) and resin composite (P-50) was performed.
      Satisfactory morphology and function of the restoration and pulp vitality were
      preserved for 17 years, thus indicating that stepwise excavation can be a good
      treatment alternative in selected cases.

PMID- 20672733
TI  - Performance of different polishing techniques for direct CAD/CAM ceramic
      restorations.
AB  - This in vitro study evaluated the performance of three ceramic and two commonly
      used polishing methods on two CAD/CAM ceramics. Surface roughness and quality
      were compared. A glazed group (GLGR) of each ceramic material served as
      reference. One-hundred and twenty specimens of VITABLOCS Mark II (VITA) and 120
      specimens of IPS Empress CAD (IPS) were roughened in a standardized manner.
      Twenty VITA and 20 IPS specimens were glazed (VITA Akzent Glaze/Empress Universal
      Glaze). Five polishing methods were investigated (n=20/group): 1) EVE Diacera
      W11DC-Set (EVE), 2) JOTA 9812-Set (JOTA), 3) OptraFine-System (OFI), 4) Sof-Lex
      2382 discs (SOF) and 5) Brownie/Greenie/Occlubrush (BGO). Polishing quality was
      measured with a surface roughness meter (Ra and Rz values). The significance
      level was set at alpha=0.05. Kruskal Wallis tests and pairwise Wilcoxon rank sum
      tests with Bonferroni-Holm adjustment were used. Qualitative surface evaluation
      of representative specimens was done with SEM. On VITA ceramics, SOF produced
      lower Ra (p<0.00001) but higher Rz values than GLGR (p=0.003); EVE, JOTA, OFI and
      BGO yielded significantly higher Ra and Rz values than GLGR. On IPS ceramics, SOF
      and JOTA exhibited lower Ra values than GLGR (p<0.0001). Equivalent Ra but
      significantly higher Rz values occurred between GLGR and EVE, OFI or BGO. VITA
      and IPS exhibited the smoothest surfaces when polished with SOF. Nevertheless,
      ceramic polishing systems are still of interest to clinicians using CAD/CAM, as
      these methods are universally applicable and showed an increased durability
      compared to the investigated silicon polishers.

PMID- 20672736
TI  - Get ready for increased scrutiny on hospital quality.

PMID- 20672735
TI  - Focus on publicly reported data enhances the case manager's role.

PMID- 20672737
TI  - Patient flow initiatives decrease LOS, up capacity.

PMID- 20672738
TI  - Hospital projects focus on patient throughput.

PMID- 20672739
TI  - Hospitalist wing patients have fewer readmissions.

PMID- 20672740
TI  - Get surging bad debt under control.

PMID- 20672741
TI  - Eliminate costly gaps in your authorizations.

PMID- 20672742
TI  - Regulatory T cells (TREG) and their roles in immune system with respect to
      immunopathological disorders.
AB  - Regulatory T cells (Tregs) are a specialized subpopulation of T cells that act to
      suppress immune response, thereby maintaining homeostasis and self-tolerance. It
      has been shown that Tregs are able to inhibit T cell proliferation and cytokine
      production and play a critical role in preventing autoimmunity. Different subsets
      with various functions of Treg cells exist. Tregs can be usually identified by
      flow cytometry. The most specific marker for these cells is FoxP3, which is
      localized intracellulary. Selected surface markers such as CD25high (high
      molecular density) and CD127low (low molecular density) could serve as surrogate
      markers to detect Tregs in a routine clinical practice. Dysregulation in Treg
      cell frequency or functions may lead to the development of autoimmune disease.
      Therapeutical Treg modulation is considered to be a promising therapeutical
      approach to treat some selected disorders, such as allergies, and to prevent
      allograft rejection.

PMID- 20672743
TI  - Osteogenic differentiation of human dental pulp-derived stem cells under various
      ex-vivo culture conditions.
AB  - Dental pulp stem cells (DPSCs) can be easily isolated and cultured in low-serum
      containing medium supplemented with growth factors PDGF-BB and EGF while
      exhibiting multipotency and immature phenotypic characteristics. In the present
      study, we investigated their potential to differentiate towards osteogenic
      lineages using various culture conditions in order to optimize their therapeutic
      use. DPSCs were cultured either as a cell monolayer or as three-dimensional (3D)
      micro-mass structures. Monolayers preincubated with bFGF and valproic acid for
      one week prior their differentiation were cultured in serum containing standard
      osteodifferentiation medium for four weeks, which resulted in multilayered nodule
      formation. Micro-mass structures were cultured for same period either in serum
      containing medium or under serum-free conditions supplemented with TGF-beta3 with
      or without BMP-2. Histochemically, we detected massive collagen I and weak
      calcium phosphate depositions in multilayered nodules. When culture 3D-aggregates
      in either standard osteodifferentiation medium or serum-free medium containing
      TGF-beta3, only small amount of collagen I fibres was observed and almost no
      deposits of calcium phosphate were detected. In contrast, in presence of both TGF
      beta3 and BMP-2 in the serum-free medium a significant amount of collagen I
      fibers/bundles and calcification were detected, which is in line with osteogenic
      effect of BMP-2. Thus, our data indicate that certain environmental cues can
      enhance differentiation process of DPSCs into osteogenic lineage, which suggest
      their possible utilization in tissue engineering.

PMID- 20672744
TI  - A comparison of the potency of newly developed oximes (K347, K628) and currently
      available oximes (obidoxime, HI-6) to counteract acute neurotoxic effects of
      Tabun in rats.
AB  - The ability of newly developed oximes (K347, K628) to reduce tabun-induced acute
      neurotoxic signs and symptoms was compared with currently available oximes
      (obidoxime, HI-6) using a functional observational battery. The neuroprotective
      effects of the oximes studied (K347, K628, obidoxime, HI-6) combined with
      atropine on rats poisoned with tabun at a sublethal dose (220 microg/kg i.m.; 80%
      of LD50 value) were evaluated. Tabun-induced neurotoxicity was monitored by a
      functional observational battery and automatic measurement of motor activity at
      24 hours following tabun challenge. The results indicate that all tested oximes
      combined with atropine enable tabun-poisoned rats to survive 24 hours following
      tabun challenge. Both newly developed oximes (K347, K628) combined with atropine
      are able to decrease tabun-induced neurotoxicity in the case of sublethal
      poisonings but they do not eliminate all tabun-induced acute neurotoxic signs and
      symptoms. Their ability to decrease the tabun-induced acute neurotoxicity is
      higher than that of the oxime HI-6 and it is slightly slower than the
      neuroprotective efficacy of obidoxime. As the neuroprotective potency of both
      newly developed oximes (K347, K628) is not as high as the potency of obidoxime,
      they are not a suitable replacement for obidoxime for the treatment of acute
      tabun poisonings.

PMID- 20672745
TI  - Stem cells from human exfoliated deciduous teeth--isolation, long term
      cultivation and phenotypical analysis.
AB  - AIMS: Our aims were to isolate stem cells from human exfoliated deciduous teeth
      (SHED), to cultivate them in vitro and to investigate their basic biological
      properties, phenotype and to compare our findings with dental pulp stem cells
      (DPSC) isolated from permanent teeth. METHODS: Dental pulp was gently evacuated
      from exfoliated teeth. After enzymatic dissociation of dental pulp, SHED were
      cultivated in modified cultivation media for mesenchymal adult progenitor cells
      containing 2% FCS and supplemented with growth factors and insulin, transferrin,
      sodium (ITS) supplement. Cell viability and other biological properties were
      examined using a Vi-Cell analyzer and a Z2-Counter. DNA analyses and phenotyping
      were performed with flow cytometry. RESULTS: We were able to cultivate SHED over
      45 population doublings. Our results showed that SHED cultivated under same
      conditions as DPSC had longer average population doubling time (41.3 hrs for SHED
      vs. 24.5 hrs for DPSC). Phenotypic comparison of cultivated SHED to that of
      cultivated DPSC showed differential expression CD29, CD44, CD71, CD117, CD 166.
      During long-term cultivation, SHED did not showed any signs of degeneration or
      spontaneous differentiation. CONCLUSIONS: We isolated stem cells from exfoliated
      teeth. In comparison to DPSC, SHED proliferation rate was about 50% slower, and
      SHED showed slightly different phenotype. These cells may be extremely useful for
      stem cell tissue banking, further stem cell research and future therapeutic
      applications.

PMID- 20672746
TI  - The role of atopy patch test in diagnosis of food allergy in atopic
      eczema/dermatitis syndrom in patients over 14 years of age.
AB  - Few studies concerning the importance of food allergy in adolescents and adult
      patients with atopic eczema exist. The atopy patch tests with food have mostly
      been studied in infants and children since food allergy plays a role especially
      in this age group. AIM: The evaluation of the contribution of atopy patch tests
      in the diagnostic work-up of food allergy (to wheat, cow milk, peanuts, soya and
      eggs) in the patients with atopic eczema older than 14 years of age. METHOD: 120
      patients were examined in the study in the diagnostic work-up of food allergy--86
      women and 34 men, the mean age 26.5 (s.d. 9.8) and the median SCORAD at the
      beginning of the study 32.9 (s.d. 14.0). Complete dermatological and
      allergological examinations in the diagnostic work-up of food allergy were
      performed (assessment of personal history, assessment of serum specific IgE, skin
      prick tests, atopy patch tests, diagnostic hypoallergenic diet, food challenge
      tests with egg, soy, wheat, cow milk and double-blind, placebo-controlled food
      challenge test with cow milk and wheat. The results of atopy patch tests were
      compared with the results of other diagnostic methods in the diagnosis of food
      allergy. RESULTS: The food allergy to cow milk and wheat was confirmed in double
      blind, placebo controlled food challenge test in few patients in our study (4%).
      The suspicion of food allergy to egg is in 8 %, to peanuts in 13 % and to soya in
      4 % of patients in our study. The assessment of atopy patch tests response seems
      to be of great importance. The reaction in atopy patch tests with more papules
      has the greatest diagnostic accuracy for predicting the result of challenge
      tests. At the beginning and at the end of diagnostic hypoallergenic diet the
      severity of atopic eczema/dermatitis syndrome was recorded in all patients
      enrolled in the study by evaluating SCORAD. The decrease of SCORAD was
      statistically important. CONCLUSION: Atopy patch tests alone cannot be used as a
      single test for the determination of food allergy in patients with atopic
      eczema/dermatitis syndrome but such a test, together with other diagnostic
      methods, can help to trace the food allergy.

PMID- 20672747
TI  - Cerebral venous thrombosis after a cesarean delivery.
AB  - Cerebral venous thrombosis (CVT) is a serious condition affecting mostly women.
      This report concerns two cases of women who developed CVT within 14 days of
      cesarean delivery. Magnetic resonance angiography of the brain (venous phase) is
      the best modality to diagnose the condition, and parenteral application of low
      molecular-weight heparin is the most beneficial treatment. The first patient was
      found to have an elevated factor VIII level. In the second patient, homozygosity
      of the C677T mutation in the 5,10-methylenetetrahydrofolate reductase gene was
      found. The puerperal period and Cesarean Section (CS) are risk factors for
      thrombotic complications, including CVT. It is necessary to search for risk
      factors in a patient's history and within the group of at-risk patients to
      prolong preventive administration of low molecular weight heparin (LMWH). CVT
      (including puerperium related) is not a detrimental to future pregnancies.

PMID- 20672748
TI  - Sarcoidosis and lung cancer.
AB  - BACKGROUND: Although sarcoidosis as well as lung cancer are frequently
      encountered common diseases, their metachronous or synchronous occurrence in the
      same patient is very rare. METHODS: The charts of lung cancer patients, diagnosed
      between 1980 and 2007 in our hospital, were reviewed. RESULTS: We found 3 cases
      with sarcoidosis and lung cancer. The first case had lung cancer 16 years after
      the diagnosis of sarcoidosis. The second case had two different metachronous lung
      cancers 18 and 10 years after the diagnosis of sarcoidosis. The third case
      detected these two diseases simultaneously. In simultaneously detected cases, it
      is difficult to determine whether noncaseating epithelioid cell granulomas
      coexisting with lung cancer represent sarcoid reaction or genuine systemic
      sarcoidosis. CONCLUSIONS: Either causality or coincidence, lung cancer, a
      condition that can be observed in patients with sarcoidosis, should be considered
      in the differential diagnosis when suspicious findings of it are discovered.

PMID- 20672749
TI  - Case 1-2010: Acute occlusion of abdominal aorta.

PMID- 20672750
TI  - [Use of "functional tooth paste," made with nanotechnology, in the treatment of
      oral mucosa diseases].
AB  - The authors report their experience connected with the introduction of
      "functional toothpaste" in Hungary. This cream (gel), prepared with
      nanotechnology, contains vitamins C and E, propolis and various herb extracts. It
      is manufactured in South Korea and is commercially available in the USA, among
      others. It protects the gingiva, and its use is recommended in cases of diseases
      of the oral mucosa. The experience in Hungary indicates that it is well
      applicable after surgery in the oral cavity (it promotes wound healing), in cases
      involving processes in the oral cavity that heal with difficulty, and during the
      healing of burn wounds (e.g. after laser surgery). In view of the favourable
      experience, its distribution in Hungary can be recommended.

PMID- 20672751
TI  - [The role of panoramic radiography in assessing the risk of injury to the
      inferior alveolar nerve before the extraction of mandibular wisdom teeth. The
      effect of the extent of root curvature and inferior alveolar canal-root tip
      overlap on the risk assessment].
AB  - The aim of the present study was to determine on panoramic radiographic images
      the effect of the distance between the root curvatures and inferior alveolar
      canal (IAC) root tip overlap on the surgeon's risk assessment predicting inferior
      alveolar nerve (IAN) paresthesia after lower third molar removal. In this case
      control study 41 cases with postoperative IAN paresthesia and 359 controls
      without any postoperative complications were involved. Demographic data, root
      curvatures and the extent of IAC-root tip overlap were registered. The cases of
      major curvature--larger than 90 degrees (P=0.015; odds ratio [OR]=2.65), the
      "deepest" superimposition (P<0.001; OR=1.96), female gender (P=0.020) and
      increased age (P=0.008) were significantly associated with IAN paresthesia.
      Assessing root curvatures and the extent of IAC-root tip overlap for predicting
      IAN paresthesia after mandibular third molar removal should help to improve risk
      assessment.

PMID- 20672752
TI  - [Etiology and diagnostics of upper canine tooth retention].
AB  - Upper canines have significant esthetical and functional roles in the dental
      arch. Upper canine retention is a frequent anomaly as the germ develops rather
      far from its final place. Moreover, the neighboring teeth may narrow the place of
      the canine because of its late eruption. Impacted canines without treatment may
      cause severe complications. Impaction of canines can be diagnosed early by
      clinical and radiological findings, which enables the clinician to perform a
      complete rehabilitation by successful surgical and orthodontic treatment.

PMID- 20672753
TI  - [A biomechanical study of Uniplant SP temporary dental implants: loading under
      laboratory conditions].
AB  - The mechanical strength parameters of Uniplant SP temporary implants were
      investigated. In clinical practice temporary implants are used to provide the
      patient with a fixed temporary restoration. Temporary implants are one-part
      implants small in diameter, and by design they have excellent primary stability.
      The temporary fixtures are usually placed simultaneously with the final implants.
      They positioned between the final implants. Due to their good stability they can
      immediately be loaded. They are usually expected to function till the final
      implants are ready for loading and when no longer needed, the temporary implants
      are removed. The abutment that carries the prosthetic components is manufactured
      in one piece with the implant, connected to it with a narrower neck portion. This
      neck part might easily fracture in the first instance when the abutment is bent
      to make abutments parallel in order to fabricate the temporary prosthetic device
      and in a second instance when temporary implants are removed. In the present
      study the mechanical properties of the cervical part were studied in a custom
      designed device. Based on the results of the loading studies recommendations were
      made to modify the current shape of the implant. With minimal modification of the
      implant design and lengthening the implant neck risk of fracture can be
      significantly reduced.

PMID- 20672754
TI  - [Combined conservative-surgical management of generalized aggressive
      periodontitis: case presentation].
AB  - The aggressive periodontitis is a well-defined clinical entity markedly differing
      from the chronic form of periodontitis. A localized and a generalized form can be
      distinguished. The main bacterial etiologic factor for the localized form is A.
      actinomycetemcomitans. It mainly starts in the first quarter of ones life. The
      magnitude of clinical attachment loss is not proportional to the amount of local
      biofilm and plaque retentive factors. The rapid, mostly vertical type of bone
      destruction is very characteristic. In many cases the attachment loss is
      localized to only a few teeth, but it may spread and progress to the generalized
      form, affecting practically the whole dentition. In that case a mixed Gram
      negative anaerobic biofilm is present subgingivally, but the AA can also dominate
      the pocket flora. Its treatment is very complex and time-consuming, and needs
      perfect patient compliance. Predictable clinical results can only be achieved by
      a combined conservative-surgical therapy. The corrective phase of the
      comprehensive treatment and patient's rehabilitation is crucial and mainly
      involves certain kind of regenerative therapy. One of the most critical phases is
      the supportive therapy. This can give a good chance to stop the progression of
      attachment loss and prevent the recurrence of the active disease. The presented
      case is to demonstrate how time-consuming a 32-year-old female patient's
      comprehensive periodontal therapy was, who had suffered with active aggressive
      periodontitis at admittance. The extensive disease control period followed by a
      relatively long follow-up and finished with a series of regenerative surgery
      could ensure a predictable outcome that might be maintained over a long period of
      time with regular supportive therapy.

PMID- 20672755
TI  - [Mistaken prognosis].

PMID- 20672756
TI  - Alice through the looking glass: the influence of self and student understanding
      on role actualization among novice clinical nurse educators.
AB  - In response to a shortage of qualified academicians, the past decade has seen
      nurses who are expert practitioners move into the role of clinical faculty.
      Although the literature on this transition is emerging, little is known about how
      expert practitioners actualize that transition or the prescribed paths to follow.
      This article describes how the understanding of self and student assists in
      actualizing the role of clinical nurse educator. The author uses a metaphor of
      Alice stepping through the looking glass to present three dimensions that expert
      practitioners pass through in their journey to clinical nurse educator. A
      conceptual model is provided to enhance clarity.

PMID- 20672757
TI  - Building an organizational culture of caring: caring perceptions enhanced with
      education.
AB  - BACKGROUND: This pilot study was undertaken to determine whether an educational
      intervention called Reigniting the Spirit of Caring (RSC) from Creative
      Healthcare Management would enhance perceptions of caring behaviors among nurses.
      A pretest/posttest within-subjects research design was used to evaluate the
      educational intervention. METHODS: Investigators used the licensed RSC program as
      the educational intervention. This study included 36 registered nurses employed
      in one Midwestern hospital. RESULTS: Statistical differences were found in the
      pretest and posttest measurement of nurses' perceptions of caring behaviors.
      CONCLUSION: The RSC program can be used as an effective educational intervention
      to increase nurses' perceptions of caring, and the Caring Assessment for the
      Caregiver tool can be used as an effective tool to measure nurses' perceptions of
      caring behaviors.

PMID- 20672758
TI  - Continued competency and board regulation: one state expands options.
AB  - State boards of nursing are mandated by state statutes to ensure the ongoing safe
      and competent practice of licensees. However, nursing practice is characterized
      by diversity in educational backgrounds, scope of practice, and variety of
      settings. As a result, regulatory agencies face many challenges. After years of
      study, the Texas Board of Nursing has identified two areas for change to the
      current regulatory model. The first area is a recommendation that nurses obtain
      continuing education credit in the individual nurse's area of practice. The
      second area is an acknowledgment of national specialty nursing certification as
      one method of demonstrating continuing competency in the nurse's specialty or
      area of practice. Both professional and vocational/practical nurses are affected
      by the rule changes.

PMID- 20672759
TI  - Academic integrity in an online registered nurse to baccalaureate in nursing
      program.
AB  - BACKGROUND: The number of nursing programs offering online courses continues to
      expand. This is a relatively new method of instruction that has not been
      extensively evaluated. Academic integrity in the online classroom is one area of
      concern. This study compared academic integrity in both an online and a
      traditional classroom registered nurse to baccalaureate in nursing (RN-BSN)
      program. METHODS: A comparative descriptive design was used to evaluate academic
      integrity in the two RN-BSN cohorts. RESULTS: The traditional classroom RN-BSN
      students reported higher levels of cheating compared with the online students.
      Self-reported cheating behaviors were higher among younger students in the
      traditional classroom. CONCLUSION: This study did not support contemporary
      concerns that cheating is more prevalent in online courses.

PMID- 20672760
TI  - New graduate nurses' perceptions of the effects of clinical simulation on their
      critical thinking, learning, and confidence.
AB  - Critical thinking has been a crucial outcome of nursing educational programs.
      Effective nurses should be knowledgeable about complex patient situations and
      confident in their skills. One teaching strategy recently adopted by some
      educators to develop nurses' critical thinking, learning, and confidence is
      simulation. Simulation incorporates scenarios and case studies developed to
      replicate real-life clinical situations. Learners are asked to solve clinical
      problems and make critical decisions based on the information provided. Little
      research has been done on how simulation experiences promote critical thinking,
      learning, and confidence, especially in new graduate nurses. This study explored
      the perceptions of new graduate nurses of how clinical simulation developed their
      critical thinking skills, learning, and confidence throughout their hospital
      clinical training. Ten new baccalaureate nursing graduates voluntarily
      participated in this study, which used an exploratory descriptive design. Data
      were collected by demographic questionnaires and semi-structured interviews and
      were analyzed using content analysis. Participants reported that simulation
      prepared them well to care confidently for critically ill patients. Simulation
      also helped them learn to make sound clinical decisions to improve patient
      outcomes. The findings have crucial implications for nursing education, practice,
      and research. They provide evidence to support the use of simulation as a
      teaching strategy to promote critical thinking skills, learning, and confidence.

PMID- 20672761
TI  - Showcasing differences between quality improvement, evidence-based practice, and
      research.
AB  - The literature confirms that much confusion exists regarding the terms quality
      improvement (QI), evidence-based practice (EBP), and research. A multifaceted
      approach was used to provide clarity regarding these three equally important
      concepts. First, the authors present a synthesis of the literature that discusses
      differences between QI, EBP, and research. Second, the authors introduce a newly
      created comparative table that synthesizes current literature and showcases
      differences between QI, EBP, and research. Finally, the authors highlight uses of
      the comparative table within multiple settings.

PMID- 20672762
TI  - Optical quality in eyes implanted with aspheric and spherical intraocular lenses
      assessed by NIDEK OPD-Scan: a randomized, bilateral, clinical trial.
AB  - PURPOSE: To determine whether implantation of an intraocular lens (IOL) with an
      aspheric surface (Akreos AO, Bausch & Lomb Inc) results in reduced ocular
      aberrations (spherical aberration) and improved Strehl ratio and modulation
      transfer function (MTF) after cataract surgery. METHODS: In an intraindividual,
      randomized, double-masked, prospective study of 50 eyes (25 patients) with
      bilateral cataract, an IOL with modified anterior and posterior surfaces (Akreos
      AO) was implanted in one eye and a biconvex IOL with spherical surfaces (Akreos
      Fit, Bausch & Lomb Inc) implanted in the fellow eye. Ocular aberrations, Strehl
      ratio, and MTF curve with 4.5-, 5.0-, and 6.0-mm pupils were measured with a
      NIDEK OPD-Scan dynamic retinoscopy aberrometer 3 months after surgery.
      Uncorrected and corrected distance visual acuity (UDVA and CDVA, respectively)
      were also measured. RESULTS: No statistically significant difference was noted
      between eyes in postoperative UDVA and CDVA at 1 month. At 3 months, the Akreos
      AO IOL group obtained statistically significant lower values of higher order and
      spherical aberrations with 4.5-, 5.0-, and 6.0-mm pupil diameters than the Akreos
      Fit IOL group (P<.05). The value of Strehl ratio was statistically significantly
      higher in eyes with the Akreos AO IOL for 4.5- and 6.0-mm pupils (P<.05). The MTF
      curve was better in the Akreos AO IOL group in 4.5-, 5.0-, and 6.0-mm pupils
      (P<.05). CONCLUSIONS: The aspheric Akreos AO IOL induced significantly less
      spherical aberration than the Akreos Fit IOL for 4.5-, 5.0-, and 6.0-mm pupils.
      Modulation transfer function and Strehl ratio were also better in eyes implanted
      with the Akreos AO IOL than the Akreos Fit.

PMID- 20672763
TI  - Refractive stability of LASIK with the Visx 20/20 excimer laser vs ZB5m phakic
      iol implantation in patients with high myopia (>-10.00 d): a 10-year
      retrospective study.
AB  - PURPOSE: To compare the long-term outcomes of LASIK and ZB5M phakic intraocular
      lens implantation (PIOL) (Domilens) for high myopia (>-10.00 diopters [D]).
      METHODS: This long-term (10 years) follow-up retrospective interventional case
      series study included 126 eyes that underwent LASIK and 52 eyes that underwent
      ZB5M angle-supported PIOL implantation. Both groups of eyes were similar in terms
      of preoperative spherical equivalent refraction (SE), corrected distance visual
      acuity (CDVA), and age. RESULTS: Mean preoperative SE was -14.33 D in the LASIK
      group and -14.84 D in the PIOL group. At 10-year follow-up, mean postoperative SE
      was -1.47+/-2.00 D in the LASIK group and -1.01+/-1.36 D in the PIOL group
      (P=.21). In the LASIK group, 67% of eyes were within +/-1.00 D of emmetropia at 2
      years after surgery, compared to 42% at 10 years. In the PIOL group, 68% of eyes
      were within +/-1.00 D of emmetropia 2 years after implantation compared to 53% at
      10 years. In the LASIK group, 43.5% of eyes achieved UDVA of 20/40 or better 10
      years after surgery compared to 67.9% in the PIOL group (P=.02). CONCLUSIONS: The
      ZB5M angle-supported PIOL was shown to have better predictability and stability
      compared to LASIK over 10 years. However, reductions in endothelial cell count
      over time were observed in eyes with PIOLs.

PMID- 20672764
TI  - Reliability of the IOLMaster in measuring corneal power changes after hyperopic
      photorefractive keratectomy.
AB  - PURPOSE: To test the accuracy of the IOLMaster (Carl Zeiss Meditec) in detecting
      corneal power changes after hyperopic photorefractive keratectomy (PRK). METHODS:
      Forty-five consecutive eyes that underwent hyperopic PRK with the SCHWIND ESIRIS
      excimer laser, ranging from +0.75 to +7.00 diopters (D) (mean: +3.84+/-1.56 D),
      were analyzed. Data included pre- and postoperative (1, 3, and 6 months) fogging
      refraction and automated keratometry (K). Statistical analysis was performed to
      determine the correlation between the changes in refraction at the corneal plane
      and the changes in keratometry. RESULTS: The mean difference between the changes
      in refraction and the measured corneal changes was +0.27+/-1.19 D (range: -1.91
      to +4.28 D) (P=.18) at 1 month; +0.56+/-0.97 D (range: -1.00 to +2.96 D) (P=.006)
      at 3 months; and +0.67+/-0.80 D (range: -0.73 to +2.31 D) (P=.00002) at 6 months.
      Based on these results, we suggest using the regression formula found at 6-month
      follow-up (y=0.8074 x + 0.092) to better calculate the effective corneal power.
      Comparison between the data obtained with IOLMaster measurements and equivalent K
      readings from the Holladay report obtained with the Pentacam (Oculus Optikgerate
      GmbH) shows good agreement (R(2)=0.9). CONCLUSIONS: Automated keratometry
      provided by the IOLMaster underestimates the effective refractive changes after
      hyperopic PRK, and a correcting factor is needed to calculate the corneal power
      in these cases.

PMID- 20672765
TI  - Editorial. Outcomes of surgery in long-standing infantile esotropia with cross
      fixation.

PMID- 20672766
TI  - Measurement of intraocular pressure with pressure phosphene tonometry in
      children.
AB  - PURPOSE: To study the accuracy and acceptability of intraocular pressure (IOP)
      measurement by the pressure phosphene tonometer, non-contact tonometer, and
      Goldmann tonometer in children. METHODS: Fifty children (5 to 14 years old)
      participated in this prospective comparative study. IOP was measured with the
      pressure phosphene tonometer, non-contact tonometer, and Goldmann tonometer by
      three different examiners who were masked to the results. The children were also
      asked to grade the degree of discomfort from 0 to 5 (0 = no discomfort; 5 = most
      discomfort). RESULTS: The mean IOPs measured by the Goldmann tonometer, pressure
      phosphene tonometer, and non-contact tonometer were 15.9 mm Hg (standard
      deviation [SD]: = 5.5 mm Hg; range: 10 to 36 mm Hg), 16.0 mm Hg (SD: 2.9 mm Hg;
      range: 12 to 25 mm Hg), and 15.7 mm Hg (SD = 5.1 mm Hg; range: 8 to 32 mm Hg),
      respectively (P = .722). The mean difference between pressure phosphene tonometer
      and Goldmann tonometer readings was 2.9 mm Hg and that between non-contact
      tonometer and Goldmann tonometer readings was 2.1 mm Hg. The 95% confidence
      interval of the mean difference between pressure phosphene tonometer and Goldmann
      tonometer readings was -1.07 and 1.19, and that between non-contact tonometer and
      Goldmann tonometer readings was -1.07 and 0.53. The mean discomfort ratings for
      the pressure phosphene tonometer, non-contact tonometer, and Goldmann tonometer
      were 0.6, 2.0, and 2.3, respectively (P < .001). CONCLUSION: Although the
      pressure phosphene tonometer was less accurate than the non-contact tonometer
      compared with Goldmann tonometer, it gave a reasonably close estimate and had a
      high specificity of raised IOP. In addition, measurement by the pressure
      phosphene tonometer is most acceptable to children. The pressure phosphene
      tonometer can be considered as an alternative method of IOP measurement in
      children.

PMID- 20672768
TI  - In vivo laser confocal microscopic analysis of corneal K-structures after
      keratorefractive surgery (LASIK and epi-LASIK).
AB  - BACKGROUND AND OBJECTIVE: To demonstrate alterations of corneal K-structures (sub
      Bowman's fibrous structures) after keratorefractive surgery by in vivo laser
      confocal microscopy and to look for association of K-structures with fluorescein
      stained anterior corneal mosaic (ACM). PATIENTS AND METHODS: Five patients (nine
      eyes) participated in this study. For four patients, one eye was evaluated after
      laser in situ keratomileusis (LASIK) and the other after epipolis-laser in situ
      keratomileusis (epi-LASIK). For one patient, the left eye was evaluated after
      epithelial debridement. A photograph of the ACM was obtained. Central corneal
      regions were scanned by Heidelberg Retina Tomograph 2 Rostock Cornea Module
      (Heidelberg Engineering GmbH, Heidelberg, Germany). RESULTS: The ACM and K
      structures disappeared in all corneas after epi-LASIK, but not after LASIK and
      epithelial debridement cornea. CONCLUSION: The presence of K-structures and ACM
      may be an index to identify eyes that had a previous refractive surgical
      procedure (surface ablation or LASIK) and be a health index of Bowman layer and
      adjacent anterior stroma.

PMID- 20672767
TI  - Are most sixth nerve palsies really paralytic?
AB  - BACKGROUND: Etiology and date of palsy are two important parameters that affect
      the treatment protocol of sixth nerve palsies. This study evaluated the treatment
      protocols and outcomes of treatment in sixth nerve palsies. METHODS: Thirty-four
      patients who had sixth nerve palsy were included. Botulinum toxin A (BTX)
      injection was performed on patients with acute sixth nerve palsy and paresis (BTX
      group), whereas chronic cases received only horizontal surgery (surgery group).
      All patients in the BTX group received a BTX injection into the ipsilateral
      medial rectus muscle. Patients in the surgery group underwent either ipsilateral
      medial rectus recession or recession combined with lateral rectus resection
      without the transposition procedure. RESULTS: Fifteen patients were treated with
      a BTX injection to the medial rectus muscle. One patient underwent ipsilateral
      medial rectus muscle recession and 6 patients received both medial rectus
      recession and lateral rectus resection in the same session. Measurement of
      esotropia was 24.9 prism diopters (PD) (range: 18 to 35 PD) before treatment in
      the BTX group. The recovery rate was 86.6% (13 of 15) without any residual
      deviation. In the surgery group, the mean preoperative deviation was 35.1 PD
      (range: 14 to 75 PD), which decreased to mean 2.57 PD (range: 0 to 10 PD)
      postoperatively. The achievement of orthotropia rate was 85.7%. CONCLUSION: BTX
      injection was found to be an effective treatment because it prevented medial
      rectus contraction in acute sixth nerve palsies. Correction of deviation with the
      recession of contracted medial rectus muscles and resection of lateral rectus
      muscles without the need of transposition in chronic sixth nerve palsy testified
      that most sixth nerve palsies involve partial paralysis rather than complete
      paralysis.

PMID- 20672769
TI  - Descemet's membrane detachment following phacoemulsification.
AB  - BACKGROUND AND OBJECTIVE: To determine the management options and the indications
      for surgical intervention in Descemet's membrane detachment (DMD) after
      phacoemulsification. PATIENTS AND METHODS: Clinical records of 11 consecutive
      eyes (11 patients) with DMD were reviewed. All cases had undergone
      phacoemulsification with posterior chamber intraocular lens implantation.
      Patients with DMD involving one-third or more of the cornea were analyzed.
      RESULTS: All patients underwent clear corneal phacoemulsification. In three cases
      where the detachment was recognized intraoperatively, perfluoropropane gas was
      injected. Eight eyes (8 cases) had unexpected corneal edema detected as DMD
      postoperatively and managed by injecting perfluoropropane gas into the anterior
      chamber. Three eyes that required repeated surgical intervention postoperatively
      had more than 50% corneal involvement with significant separation of the membrane
      from the stroma and curling or folding of the membrane. At last follow-up, 10
      eyes retained clear corneas and one had residual DMD not involving visual axis.
      All 11 eyes had best-corrected visual acuity of better than 6/12. CONCLUSION: DMD
      should be suspected in patients showing unexpected corneal edema postoperatively
      who have undergone uneventful phacoemulsification and be treated in a timely
      manner. Surgical intervention is recommended in cases with significant separation
      of the membrane from stroma and curling or folding of the Descemet's membrane.

PMID- 20672770
TI  - Trainee glaucoma surgery: experience with trabeculectomy and glaucoma drainage
      devices.
AB  - BACKGROUND AND OBJECTIVE: To examine outcomes of trabeculectomy with mitomycin C
      and glaucoma drainage device placement for uncontrolled glaucoma when performed
      by resident surgeons. PATIENTS AND METHODS: This study included any patient who
      underwent a trabeculectomy with mitomycin C (n = 93) or a glaucoma drainage
      device (n = 60) by a resident surgeon between 2001 and 2006. Outcome measures at
      3, 6, and 12 months included failure of treatment, number of follow-up
      appointments, complications, number of medications, and need for further surgery.
      RESULTS: One year postoperatively, intraocular pressure averaged 12.1 +/- 5.1 mm
      Hg in the trabeculectomy group and 13.0 +/- 5.1 mm Hg in the glaucoma drainage
      device group (P = .31). Complications occurred in 30% of eyes with trabeculectomy
      and 10% of eyes with a glaucoma drainage device. CONCLUSION: During the first
      postoperative year, glaucoma drainage device surgery may have fewer complications
      and less morbidity than a trabeculectomy with mitomycin C when these surgeries
      are performed by resident surgeons. Final intraocular pressures were similar
      between the two groups.

PMID- 20672771
TI  - Prospective, contralateral comparison of 120-MUm and 90-MUm LASIK flaps using the
      IntraLase FS60 femtosecond laser.
AB  - PURPOSE: To compare differences in visual acuity, contrast sensitivity, higher
      order ocular aberrations, quality of life, and patient-reported outcomes at 3 and
      6 months postoperatively in eyes with stable myopia undergoing thin-flap
      (intended flap thicknesses of 120 or 90 MUm) LASIK using the VISX Star S4
      CustomVue excimer laser (VISX Inc), with flaps created by the IntraLase FS60
      femtosecond laser (Abbott Medical Optics). METHODS: In this prospective study,
      thin-flap LASIK was performed contralaterally on 94 eyes: 47 eyes with 120-MUm
      intended flap thickness and 47 eyes with 90-MUm intended flap thickness. Primary
      outcome measures were uncorrected distance visual acuity (UDVA), corrected
      distance visual acuity (CDVA), contrast sensitivity, and higher order
      aberrations. RESULTS: At 6 months, mean values for UDVA (logMAR) were -0.064+/
      0.077 and -0.051+/-0.070 in the 120-MUm and 90-MUm groups, respectively (n=40,
      P=.431). Visual acuity of 20/20 was achieved in 98% of eyes with 120-MUm flaps
      and 95% of eyes with 90-MUm flaps, whereas 20/15 vision was achieved in 50% of
      eyes with 120-MUm flaps and 45% of eyes with 90-MUm flaps (P>=.454). Both groups
      had significant increases in total higher order aberrations (P<=.003).
      Significant differences were not found between groups in contrast sensitivity
      (P>=.258), CDVA (P>=.726), total higher order aberrations (P>=.477), or patient
      reported outcomes (P>=.132). Patients in both groups reported increased quality
      of life postoperatively (P<=.002). CONCLUSIONS: Under well-controlled surgical
      conditions, thin-flap LASIK achieved similar results in visual acuity, contrast
      sensitivity, and low induction of higher order aberrations in eyes with intended
      flap thicknesses of either 120 or 90 MUm.

PMID- 20672772
TI  - Corneal density with the Pentacam after photorefractive keratectomy.
AB  - PURPOSE: To measure corneal density and evaluate corneal haze in unoperated eyes
      and in eyes after photorefractive keratectomy (PRK). METHODS: Forty-nine patients
      (91 eyes) who underwent PRK and 48 control patients (76 unoperated eyes) were
      measured with the densitometry program of the Pentacam Scheimpflug imaging system
      (Oculus Optikgerate GmbH) (0=no clouding, 100=tissue completely opaque). Eyes
      were categorized as myopic or hyperopic (myopia group and hyperopia group), with
      subgroups defined as unoperated (unoperated myopia group and unoperated hyperopia
      group), postoperative clear corneas (clear cornea myopia group and clear cornea
      hyperopia group), and postoperative with haze (myopia haze group and hyperopia
      haze group). The ANOVA option of the Statistica 8.1 program package (StatSoft
      Inc) was used to compare subgroups. RESULTS: Maximum density of postoperative
      corneas with haze (myopia haze group, 46.2+/-16.2; hyperopia haze group, 50.2+/
      25.8) was higher than in postoperative clear corneas (clear cornea myopia group,
      29.9+/-8.7; clear cornea hyperopia group, 22.9+/-3.1), but maximum corneal
      density in the latter subgroups showed no difference compared with unoperated
      controls (unoperated myopia group, 25.1+/-2.4; unoperated hyperopia group, 22.8+/
      3.2). Differences among subgroups were not found outside the 6-mm diameter
      ablation zone. In hazy myopic corneas, there was a strong decreasing density
      trend from the apex to the 3-mm radius (P<.001, R=-0.5), which continued towards
      the periphery at 4.5 mm (P=.019, R=-0.21). Hyperopic mild hazy corneas showed a
      density increase from the apex to 3 mm (P<.001, R=0.4), followed by a decrease
      towards the periphery (P<.01, R=-0.4). CONCLUSIONS: The densitometry program of
      the Pentacam can provide a useful objective measure of postoperative and other
      mild corneal haze.

PMID- 20672773
TI  - Posterior corneal elevation after LASIK with three flap techniques as measured by
      Pentacam.
AB  - PURPOSE: To evaluate and compare posterior corneal changes using elevation data
      obtained from Pentacam (Oculus Optikgerate GmbH) Scheimpflug imaging in eyes
      undergoing LASIK with three different modes of flap creation: IntraLase
      femtosecond laser FS60 (Abbott Medical Optics) (femtosecond group), Amadeus
      (Ziemer Group AG) mechanical microkeratome (keratome group), or flap formation
      using 20% alcohol laser epithelial keratomileusis (LASEK) (LASEK group). METHODS:
      Ninety myopic patients (90 eyes) undergoing refractive surgery were recruited.
      The change in posterior corneal elevation at 21 predetermined points in the
      central 5-mm area was measured using exported elevation data from the Pentacam
      before LASIK and 18 months postoperative and was compared among and within three
      modes of flap creation. RESULTS: Mean change in posterior elevation in the
      central 5-mm area was 5.13+/-4.16 MUm for the femtosecond group, 5.78+/-4.42 MUm
      for the keratome group, and 6.68+/-4.72 MUm for the LASEK group and was similar
      among groups (P=.59). Change in posterior elevation before and after LASIK was
      not significant within any group (P=.342, P=.232, and P=.321 for the femtosecond,
      keratome, and LASEK groups, respectively). Preoperative spherical equivalent,
      central corneal thickness, ablation depth, and estimated residual bed thickness
      did not correlate with change in posterior corneal elevation for the femtosecond,
      keratome, or LASEK groups (P>.05). CONCLUSIONS: Using Pentacam elevation data,
      there were no significant changes in posterior corneal elevation following LASIK
      among or within the three methods of flap creation. At 18 months after LASIK, the
      posterior corneal surface is not displaced anteriorly significantly and is
      equally stable using these three surgical techniques.

PMID- 20672774
TI  - A bold adventure in innovation: an international off-campus master's degree
      program.
AB  - In response to the global shortage of nursing faculty, Loma Linda University
      School of Nursing offered an off-campus master's degree program to prepare nurse
      educators who would commit to remain in their home countries following
      graduation. The program was approved by the Western Association of Schools and
      Colleges to be offered in both English and Spanish. Students and faculty met for
      1 month each year for 4 years at one of two international sites: Thailand or
      Argentina. Forty-five of 49 students completed the program. The cultural
      diversity in both cohorts enriched classroom discussions, social interaction, and
      student-faculty conversations. The program was a life-changing experience for all
      involved and helped to meet the global need for nursing faculty. The faculty
      reported that it broadened their world view and opened their minds to the
      potential for innovation to transform nursing education.

PMID- 20672775
TI  - Development of simulation scenarios for an adolescent patient with diabetic
      ketoacidosis.
AB  - Changes in health care delivery have shifted the care of pediatric patients
      primarily to the outpatient setting, with the exception of children and
      adolescents requiring complex, highly acute care. Thus, nurse educators are
      challenged to provide nursing students with pediatric learning experiences and
      are further confounded by the relative paucity of available clinical placements.
      Nurse educators are exploring the use of simulation to provide realistic
      alternatives to pediatric clinical experiences. The development of simulation
      scenarios focused on the care of an adolescent patient presenting with diabetic
      ketoacidosis is discussed. A review of the current literature addressing the use
      of simulation in nursing education and the advantages and challenges of
      designing, implementing, and evaluating simulation scenarios are also discussed.

PMID- 20672776
TI  - Quality and safety education for nurses clinical evaluation tool.
AB  - An efficient evaluation tool is essential when measuring the clinical performance
      of undergraduate nursing students. It is also important that this evaluation tool
      accurately assess the critical competencies that students must demonstrate in the
      clinical setting. The tool should be unambiguous, succinct, and adaptable to a
      wide variety of clinical experiences and faculty. As part of a curriculum
      improvement initiative for their baccalaureate nursing program, the nursing
      faculty teaching in a 4-year undergraduate program identified the need for the
      development of a new clinical performance evaluation tool for the evaluation of
      undergraduate nursing students in each clinical placement. The resultant tool
      more accurately appraised clinical capabilities by focusing on quality and safety
      in health care, and it permitted the evaluation of critical thinking skills and
      team communication.

PMID- 20672777
TI  - A systematic review of the effectiveness of remediation interventions to improve
      NCLEX-RN pass rates.
AB  - First-time NCLEX-RN pass rates are important measures of educational quality in
      prelicensure nursing education programs. Licensure pass rate problems has been
      the subject of countless nursing education articles and studies over the past
      several decades. To improve NCLEX-RN pass rates, remediation is often prescribed
      for students who have academic performance deficits. This article presents a
      systematic review of studies on remediation interventions and their effects on
      NCLEX-RN pass rates. Most studies of remediation and its effects on licensure
      pass rates are descriptive program evaluation reports. The overall quality of
      studies included in this review is uneven but generally low. Nursing education
      researchers should focus on conducting higher quality intervention studies in
      which the fidelity of remediation interventions can be examined. Viewing
      licensure pass rates from a process improvement perspective and accounting for
      pass rate variations could also change the nature of scholarship on this topic.

PMID- 20672778
TI  - A mentor-protege program for new faculty, part I: stories of proteges.
AB  - With the projected shortage of nursing faculty, formalized programs are needed to
      provide mentorship programs that will encourage and support faculty as they move
      from the role of novice to expert educator. The purpose of this qualitative study
      is to explore the experience of proteges participating in a mentorship program
      for novice faculty. An interpretive phenomenological research study was conducted
      to illuminate the meaning of the experiences of the proteges participating in the
      program. The study of the experience of proteges participating in a mentor
      protege program led to the emergence of three main themes: Creating a Meaningful
      Mentor-Protege Relationship, Transitioning as a New Nurse Educator, and the
      Mentor-Protege Program-Lessons Learned. Data from the study will provide insight
      into the meaning of receiving mentorship in the role of novice nurse educator.

PMID- 20672779
TI  - Embracing multiculturalism in nursing learning environments.
AB  - This article outlines the disparities that exist in educational opportunities for
      ethnic minorities in both higher education and nursing programs. Barriers exist
      for ethnic minorities that are directly related to students' circumstances and
      factors related to faculty and universities. There are multiple strategies that
      can be implemented by faculty and universities to ameliorate inequities in
      education, but they are most meaningful when institutions use self-reflection and
      plan for long-term sustainable changes.

PMID- 20672780
TI  - Drawing from the outside for support in teaching.
AB  - Mentoring new nurse educators in their pedagogy is vital to their long-term
      success and their students' learning. It is also crucial to build mentoring into
      ongoing professional development plans because doctoral studies rarely include
      information on how to be an effective teacher. An overlooked resource on college
      campuses is the education department. This article describes the processes of a
      fruitful 2-year mentoring relationship between a new nurse educator and an
      education professor and offers a virtually no-cost strategy for improving the
      quality of teaching in schools, departments, and colleges of nursing. Using
      education faculty as mentors has two advantages over using fellow nursing
      faculty: pedagogy is their absolute professional expertise and the relationship
      may be less fraught with the potential baggage of peer evaluation because the
      mentors and mentees are in different departments. Trust, open communication, and
      clear goal-setting establish the framework for successful mentoring
      relationships.

PMID- 20672781
TI  - Expanding simulation to teach family nursing.
AB  - Caring for families during an illness experience is increasingly recognized as a
      core of nursing practice. Yet research reports deficiencies in the current state
      of family nursing care. It is possible that these deficiencies are rooted in a
      lack of integrating family care throughout nursing education and a focus on the
      biomedical science paradigm. As a relational skill, family care requires
      different pedagogical approaches to effectively teach family nursing. Simulation
      is one such approach. Even though simulation is rapidly moving into nursing
      education, the primary focus is teaching psychomotor nursing skills, rather than
      caring and family nursing.

PMID- 20672782
TI  - Encouraging physical activity among frail older adults.

PMID- 20672785
TI  - Evidence for global CHD risk calculation: risk assessment alone does not change
      outcomes.

PMID- 20672786
TI  - Neuraminidase inhibitors for influenza treatment and prevention in healthy
      adults.

PMID- 20672787
TI  - Medical management vs. surgery for gastroesophageal reflux disease.

PMID- 20672788
TI  - Diagnosis and management of contact dermatitis.
AB  - Contact dermatitis is a common inflammatory skin condition characterized by
      erythematous and pruritic skin lesions that occur after contact with a foreign
      substance. There are two forms of contact dermatitis: irritant and allergic.
      Irritant contact dermatitis is caused by the non-immune-modulated irritation of
      the skin by a substance, leading to skin changes. Allergic contact dermatitis is
      a delayed hypersensitivity reaction in which a foreign substance comes into
      contact with the skin; skin changes occur after reexposure to the substance. The
      most common substances that cause contact dermatitis include poison ivy, nickel,
      and fragrances. Contact dermatitis usually leads to erythema and scaling with
      visible borders. Itching and discomfort may also occur. Acute cases may involve a
      dramatic flare with erythema, vesicles, and bullae; chronic cases may involve
      lichen with cracks and fissures. When a possible causative substance is known,
      the first step in confirming the diagnosis is determining whether the problem
      resolves with avoidance of the substance. Localized acute allergic contact
      dermatitis lesions are successfully treated with mid- or high-potency topical
      steroids, such as triamcinolone 0.1% or clobetasol 0.05%. If allergic contact
      dermatitis involves an extensive area of skin (greater than 20 percent), systemic
      steroid therapy is often required and offers relief within 12 to 24 hours. In
      patients with severe rhus dermatitis, oral prednisone should be tapered over two
      to three weeks because rapid discontinuation of steroids can cause rebound
      dermatitis. If treatment fails and the diagnosis or specific allergen remains
      unknown, patch testing should be performed.

PMID- 20672789
TI  - Contact dermatitis: what you should know.

PMID- 20672790
TI  - Slipped capital femoral epiphysis: diagnosis and management.
AB  - Slipped capital femoral epiphysis is the most common hip disorder in adolescents,
      and it has a prevalence of 10.8 cases per 100,000 children. It usually occurs in
      children eight to 15 years of age, and it is one of the most commonly missed
      diagnoses in children. Slipped capital femoral epiphysis is classified as stable
      or unstable based on the stability of the physis. The condition is associated
      with obesity and growth surges, and it is occasionally associated with endocrine
      disorders such as hypothyroidism, growth hormone supplementation, hypogonadism,
      and panhypopituitarism. Patients usually present with limping and poorly
      localized pain in the hip, groin, thigh, or knee. Diagnosis is confirmed by
      bilateral hip radiography, which needs to include anteroposterior and frog-leg
      lateral views in patients with stable slipped capital femoral epiphysis, and
      anteroposterior and cross-table lateral views in patients with the unstable form.
      The goals of treatment are to prevent slip progression and avoid complications
      such as avascular necrosis and chondrolysis. Stable slipped capital femoral
      epiphysis is usually treated using in situ screw fixation. Treatment of unstable
      slipped capital femoral epiphysis usually involves in situ fixation, but there is
      controversy about the timing of surgery, value of reduction, and whether traction
      should be used.

PMID- 20672791
TI  - Global risk of coronary heart disease: assessment and application.
AB  - Coronary heart disease is the most common cause of death in the United States.
      The conventional risk factor approach to primary prevention excludes many
      patients who could benefit from preventive therapies. A global risk approach
      allows more accurate estimates of risk to guide clinical primary prevention
      efforts. Global risk of coronary heart disease is a calculation of the absolute
      risk of having a coronary heart disease event (e.g., death, myocardial
      infarction) over a specified period. It is based on an empiric equation that
      combines major risk factors, such as blood pressure and cholesterol levels. When
      physicians know a patient's global risk of coronary heart disease, they are more
      likely to prescribe risk-reducing therapies such as antihypertensives, statins,
      and aspirin. In addition, patients who know their risk level are more likely to
      initiate risk-reducing therapies. Many tools are available to estimate global
      risk, including several Web-based calculators. In the United States, tools based
      on the Framingham Heart Study are recommended.

PMID- 20672792
TI  - Heart attack: what is your risk?

PMID- 20672793
TI  - Acutely swollen tongue in a middle-aged woman.

PMID- 20672794
TI  - Time to chat.

PMID- 20672796
TI  - High efficiency CD91- and LOX-1-mediated re-presentation of gp96-chaperoned
      peptides by MHC II molecules.
AB  - Exogenous antigens enter antigen-presenting cells through non-specific mechanisms
      and are presented by the MHC II molecules. We show here that antigens chaperoned
      by the heat shock protein gp96 enter dendritic cells and B cells through a
      specific, CD91- and LOX-1-mediated mechanism, and are presented by MHC II
      molecules, in addition to MHC I molecules as previously demonstrated. Receptor
      utilization results in high efficiency uptake such that antigen concentrations as
      low as 10(-9) M, if chaperoned by gp96, lead to productive antigen presentation.
      Chaperoning by gp96 increases the efficiency of uptake over un-chaperoned
      peptides by up to two orders of magnitude. Consistent with these studies in
      vitro, immunization of mice with gp96-peptide complexes (containing 5 ng peptide)
      results in generation of a peptide-specific CD4+ T cell response. The high
      efficiency suggests a mechanism in which dendritic cells, exposed in vivo to heat
      shock protein-chaperoned peptides liberated by virus-infected host cells or by
      the lysis of infecting bacteria, may prime and expand specific CD4+ responses.

PMID- 20672797
TI  - Peptide interactions with metal and oxide surfaces.
AB  - Increasing interest in bio-interfaces for medical, diagnostic, or biotechnology
      applications has highlighted the critical scientific challenge behind both the
      understanding and control of protein-solid surface interactions. In this context,
      this Account focuses on the molecular-level characterization of the interactions
      of peptides, ranging in size from a few amino acids to long sequences, with metal
      and oxide surfaces. In this Account, we attempt to fill the gap between the well
      known basic studies of the interaction of a single amino acid with well-defined
      metal surfaces and the investigations aimed at controlling biocompatibility or
      biofilm growth processes. We gather studies performed with surface science tools
      and macroscopic characterization techniques along with those that use modeling
      methods, and note the trends that emerge. Sulfur drives the interaction of
      cysteine-containing peptides with metal surfaces, particularly gold. Moreover,
      intermolecular interactions, such as hydrogen bonds may induce surface self
      assembly and chiral arrangements of the peptide layer. Depending on the solvent
      pH and composition, carboxylates or amino groups may also interact with the
      surface, which could involve conformational changes in the adsorbed peptide. On
      oxide surfaces such as titania or silica, researchers have identified carboxylate
      groups as the preferential peptide binding groups because of their strong
      electrostatic interactions with the charged surface. In high molecular weight
      peptides, systematic studies of their interaction with various oxide surfaces
      point to the preferential interaction of certain peptide sequences: basic
      residues such as arginine assume a special role. Researchers have successfully
      used these observations to synthesize adhesive sequences and initiate
      biomineralization. Studies of the interaction of peptides with nanoparticles have
      revealed similar binding trends. Sulfur-containing peptides adhere preferentially
      to gold nanoparticles. Peptides containing aromatic nitrogen also display a high
      affinity for various inorganic nanoparticles. Finally, we describe a novel class
      of peptides, genetically engineered peptides for inorganics (GEPIs), which are
      selected from a phage display protocol for their high binding affinity for
      inorganic surfaces. Extended investigations have focused on the mechanisms of the
      molecular binding of these peptides to solid surfaces, in particular the high
      binding affinity of some sulfur-free sequences of GEPIs to gold or platinum
      surfaces. We expect that this clearer view of the possible preferential
      interactions between peptides and inorganic surfaces will facilitate the
      development of new, more focused research in various fields of biotechnology,
      such as biocompatibility, biomimetics, or tissue engineering.

PMID- 20672798
TI  - Synthesis of alpha-amino acids based on chiral tricycloiminolactone derived from
      natural (+)-camphor.
AB  - Amino acids are one of the most important classes of the building blocks of life:
      they are the structural subunits of proteins, peptides, and many secondary
      metabolites. In addition to the 20 alpha-amino acids that constitute the backbone
      of proteins, hundreds of other natural alpha-amino acids have been discovered
      either in free form or as components in natural products. The difference between
      these molecules is the substituents at the chiral carbon situated between the
      amino and carboxyl moieties; this carbon (and any atom along a chain attached to
      it) is thus an important synthetic target. Because tailor-made alpha-amino acids
      are increasingly popular in biochemistry and organic synthesis, further
      refinement in synthetic methods to generate both natural (L-configuration) and
      unnatural (D-configuration) amino acids is a very active area of current
      research. In this Account, we examine the tricycloiminolactones, which are
      versatile glycine equivalents derived from natural camphor. We have developed the
      tricycloiminolactones in our laboratory and used them in the synthesis of several
      kinds of enantiopure alpha-amino acids. As nucleophiles, enolated
      tricycloiminolactones were shown to successfully participate in alkylations,
      Aldol reactions, Michael additions, and Mannich reactions. These reactions all
      gave excellent stereoselectivities and high yields. Simple conversion of the
      products offered alpha-alkyl-alpha-amino acids, alpha,alpha-dialkyl-alpha-amino
      acids, beta-hydroxy-alpha-amino acids, alpha,gamma-diamino acids, and alpha,beta
      diamino acids. One particular advantage is that the same electrophile can react
      with two chiral templates in the same way, thus affording access to both
      enantiomeric amino acids. In other words, some natural (L-configuration) alpha
      amino acids and their unnatural (D-configuration) counterparts can be prepared
      very conveniently. The relation between substrate structures and product
      stereoconformations derived from our investigations serves as a convenient guide
      in the synthesis of useful chiral amino acids. In addition, highly
      stereoselective 1,3-diploar cycloadditions between alkenes and chiral nitrones
      derived from tricycloiminolactones provide a potential method for the synthesis
      of gamma-hydroxy-alpha-amino acids. We also discuss applications of our methods
      in the synthesis of complex natural products, including conagenin, polyoxamic
      acid, lactacystin, and sphingofungin F. The preparation of some clinically
      important drug molecules, such as thiaphenicol, florfenicol, and chloramphenicol,
      was greatly simplified with our methods. The tricycloiminolactones offer a number
      of advantages in the synthesis of both natural and unnatural alpha-amino acids
      and provide many useful building blocks in the synthetic pursuit of complex
      molecules.

PMID- 20672799
TI  - Visualization of a discrete solid-state process with steady-state X-ray
      diffraction: observation of hopping of sulfur atoms in single crystals of
      realgar.
AB  - A molecular movie showing migration of a sulfur atom between molecules of realgar
      (alpha-As(4)S(4)) was obtained by a series of structure determinations of the
      dark stage of this all-solid autocatalytic reaction set.

PMID- 20672800
TI  - Synthesis of high-Curie-temperature Fe0.02Ge0.98 quantum dots.
AB  - Self-assembled Fe(0.02)Ge(0.98) dilute magnetic quantum dots show a high Curie
      temperature above 400 K. Such extraordinary magnetic properties can potentially
      resolve the critical problem of power dissipation in today's integrated circuits
      and lead to the realization of a new class of spintronics devices.

PMID- 20672801
TI  - Stopped-flow NMR: determining the kinetics of [rac-(C2H4(1
      indenyl)2)ZrMe][MeB(C6F5)3]-catalyzed polymerization of 1-hexene by direct
      observation.
AB  - Stopped-flow NMR measurements suitable for determination of reaction kinetics on
      time scales of 100 ms or longer have been achieved by adaptation of a commercial
      NMR flow probe with a high-efficiency mixer and drive system. Studies of
      metallocene-catalyzed alkene polymerization at room temperature have been
      complicated by high rates, imprecise knowledge of the distribution of different
      catalyst species with time, and the high sensitivity of the catalysts to low
      concentrations of impurities. Application of the stopped-flow NMR method to the
      study of the kinetics of 1-hexene polymerization in the presence of
      (EBI)ZrMe[MeB(C(6)F(5))(3)] demonstrates that NMR spectroscopy provides an
      efficient method for direct and simultaneous measurement of substrate consumption
      and catalyst speciation as a function of time. Kinetic modeling of the catalyst
      and substrate concentration time courses reveal efficient determination of
      initiation, propagation, and termination rate constants. As first suggested by
      Collins and co-workers (Polyhedron 2005, 24, 1234-1249), a kinetic model in which
      Zr-HB(C(6)F(5))(3) forms rapidly upon beta-hydride elimination but reacts
      relatively slowly with alkene to reinitiate chain growth is supported by these
      data.

PMID- 20672802
TI  - Water oxidation by lambda-MnO2: catalysis by the cubical Mn4O4 subcluster
      obtained by delithiation of spinel LiMn2O4.
AB  - Nanocrystalline spinel LiMn(2)O(4) has been prepared and treatment of LiMn(2)O(4)
      with dilute nitric acid solution resulted in the delithiation of the framework,
      while maintaining the spinel structure, lambda-MnO(2). LiMn(2)O(4) is not a
      catalyst for water oxidation. Upon removal of the lithium, the cubical Mn(4)O(4)
      cores become active sites for oxidizing water to molecular oxygen, which was
      investigated with the photochemical [Ru(2+)(2,2'-bpy)(3)]/persulfate system at pH
      5.8. The nanosize lambda-MnO(2) obtained from the nanocrystalline LiMn(2)O(4),
      which was synthesized by the citrate route, shows a significantly higher water
      oxidation catalytic activity (Turnover Frequency: 3 x 10(-5) mol O(2)/s/mol Mn)
      than that obtained via solid state reaction with micrometer and irregular
      particle sizes (Turnover Frequency: 5 x 10(-6) mol O(2)/s/mol Mn).

PMID- 20672803
TI  - Thermodynamic versus kinetic control of antioxidant synergism between beta
      carotene and (iso)flavonoids and their glycosides in liposomes.
AB  - Antioxidant synergism (or antagonism) between plant (iso)flavonoids (daidzein,
      baicalein, and quercetin) or their glycosides (puerarin, baicalin, and rutin) and
      beta-carotene in phosphatidylcholine liposomes (pH 7.4) with oxidation initiated
      thermally by the lipophilic free radical initiator 2,2'-azobis(2,4
      dimethylvaleronitrile) (AMVN) and followed by the formation of conjugated dienes
      did not depend simply on the bond dissociation enthalpy (BDE) of the phenol O-H
      bond or the HOMO/LUMO energy gap based on density functional theory (DFT)
      calculations. Rate of regeneration of beta-carotene from the beta-carotene
      radical cation as the one-electron oxidation product of the lipid phase
      antioxidant by the monoanion form of the (iso)flavonoids in homogeneous (1:9 v/v
      methanol/chloroform) solution, as studied by laser flash photolysis and occurring
      on a microsecond time scale with biphasic kinetics, was in better agreement with
      the observed nonadditive antioxidative effects. However, correcting the observed
      (pseudo)-first-order rate constant for beta-carotene regeneration for water/lipid
      distribution of the (iso)flavonoids provided an almost correct ordering of the
      (iso)flavonoids, according to the nonadditive effects with beta-carotene on lipid
      oxidation.

PMID- 20672804
TI  - Shifting the equilibrium between the encounter state and the specific form of a
      protein complex by interfacial point mutations.
AB  - Recent experimental studies have confirmed a long-held view that protein complex
      formation proceeds via a short-lived encounter state. The population of this
      transient intermediate, stabilized mainly by long-range electrostatic
      interactions, varies among different complexes. Here we show that the occupancy
      of the encounter state can be modulated across a broad range by single point
      mutations of interfacial residues. Using a combination of Monte Carlo simulations
      and paramagnetic relaxation enhancement NMR spectroscopy, we illustrate that it
      is possible to both enhance and diminish the binding specificity in an electron
      transfer complex of yeast cytochrome c (Cc) and cytochrome c peroxidase. The Cc
      T12A mutation decreases the population of the encounter to 10% as compared with
      30% in the wild-type complex. More dramatically, the Cc R13A substitution
      reverses the relative occupancies of the stereospecific and the encounter forms,
      with the latter now being the dominant species with the population of 80%. This
      finding indicates that the encounter state can make a large contribution to the
      stability of a protein complex. Also, it appears that by adjusting the amount of
      the encounter through a judicious choice of point mutations, we can remodel the
      energy landscape of a protein complex and tune its binding specificity.

PMID- 20672806
TI  - Improved Arndt-Eistert synthesis of alpha-diazoketones requiring minimal
      diazomethane in the presence of calcium oxide as acid scavenger.
AB  - A practical methodology to obtain alpha-diazoketones through an improved Arndt
      Eistert synthesis is described. The method allows the efficient transformation of
      acid halides using a stoichiometric amount of diazomethane in the presence of
      calcium oxide, without concomitant ketene or haloketone formation. The obtained
      alpha'-brominated-alpha-diazoketones were employed as suitable substrates for the
      synthesis of interesting alpha-arylamino-alpha'-halomethylketones.

PMID- 20672805
TI  - Small molecules that modulate quorum sensing and control virulence in Pseudomonas
      aeruginosa.
AB  - Bacteria use small molecule signals to access their local population densities in
      a process called quorum sensing (QS). Once a threshold signal concentration is
      reached, and therefore a certain number of bacteria have assembled, bacteria use
      QS to change gene expression levels and initiate behaviors that benefit the
      group. These group processes play central roles in both bacterial virulence and
      symbiosis and can have significant impacts on human health, agriculture, and the
      environment. The dependence of QS on small molecule signals has inspired organic
      chemists to design non-native molecules that can intercept these signals and
      thereby perturb bacterial group behaviors. The opportunistic pathogen Pseudomonas
      aeruginosa has been the target of many of these efforts due to its prevalence in
      human infections. P. aeruginosa uses at least two N-acyl l-homoserine lactone
      signals and three homologous LuxR-type receptors to initiate a range of
      pathogenic behaviors at high cell densities, including biofilm formation and the
      production of an arsenal of virulence factors. This perspective highlights recent
      chemical efforts to modulate LuxR-type receptor activity in P. aeruginosa and
      offers insight into the development of receptor-specific ligands as potential
      antivirulence strategies.

PMID- 20672807
TI  - Palladium-catalyzed synthesis of enantiomerically pure alpha-substituted
      allylboronic esters and their addition to aldehydes.
AB  - Tartrate-derived boronic esters 2 can be subjected to palladium-catalyzed
      carbonyl allylations with SnCl(2) to obtain enantiomerically pure alpha
      substituted allylboronic esters 8 and 9. The reaction proceeds regioselectively
      and with high, simple diastereoselectivity to form anti-products. Their addition
      to aldehydes yields enantiomerically enriched homoallylic alcohols 17 and 18,
      respectively. Synthesis, characterization, and a mechanistic rational is
      presented here.

PMID- 20672808
TI  - N-H activation of hydrazines by iridium(I). Double N-H activation to form iridium
      aminonitrene complexes.
AB  - Iridium(I) complexes of aromatic (PCP) and aliphatic (D(t)BPP) pincer ligands
      undergo single cleavage of the N-H bonds of hydrazine derivatives to form
      hydrazido complexes and geminal double cleavage to form unusual late transition
      metal aminonitrene complexes. In some cases, the cleavage of the N-N bond in the
      hydrazine is also observed. Oxidative additions of the N-H bonds of benzophenone
      hydrazone and 1-aminopiperidine to iridium(I) complexes give the corresponding
      hydridoiridium(III) hydrazido complexes within minutes. The complex containing an
      aromatic pincer ligand, (PCP)Ir(H)(NHNC(5)H(10)), slowly undergoes a second N-H
      bond cleavage at the alpha-N-H bond and elimination of hydrogen to generate an
      aminonitrene complex and dihydrogen in high yield. The reactions of the
      (PCP)Ir(I) fragment containing an aromatic pincer ligand with methyl-substituted
      hydrazines form a mixture of aminonitrene complexes, isocyanide iridium(III)
      dihydride complexes, and ammonia. The latter two products are likely formed by
      initial oxidative addition of the methyl C-H bond and the subsequent N-N bond
      cleavage. Reactions of the aminonitrene complex with CO or reagents that undergo
      oxidative addition (MeI and PhOH) lead to release of the "isodiazine" fragment to
      give tetrazene and tetrazine derivatives.

PMID- 20672809
TI  - Design, validation, and implementation of a rapid-injection NMR system.
AB  - A Rapid Injection NMR (RINMR) apparatus has been designed and constructed to
      allow the observation of fast chemical reactions in real time by NMR
      spectroscopy. The instrument was designed to allow the rapid (<2 s) injection and
      mixing of a metered volume of a reagent into a spinning NMR tube followed by
      rapid acquisition of the data resulting from the evolution of the chemical
      process. The various design criteria for this universal system included the
      ability to deliver any chemical reagent at any temperature and allow for the
      observation of any nucleus. The various challenges associated with the
      construction and implementation of this instrument are documented along with the
      validation of the accuracy of the apparatus with respect to volume and
      temperature. Finally, the ultimate validation and reproducibility of the
      technique is presented in the form of three case studies that used the instrument
      to elucidate various aspects of organic reaction mechanisms. The authors urge
      interested parties to not embark on the construction of their own instrument and
      invite those whose research problems might be amenable to this kind of analysis
      to contact the corresponding author for access to the apparatus described herein.

PMID- 20672810
TI  - A general and efficient catalyst for palladium-catalyzed C-O coupling reactions
      of aryl halides with primary alcohols.
AB  - An efficient procedure for palladium-catalyzed coupling reactions of (hetero)aryl
      bromides and chlorides with primary aliphatic alcohols has been developed. Key to
      the success is the synthesis and exploitation of the novel bulky di-1-adamantyl
      substituted bipyrazolylphosphine ligand L6. Reaction of aryl halides including
      activated, nonactivated, and (hetero)aryl bromides as well as aryl chlorides with
      primary alcohols gave the corresponding alkyl aryl ethers in high yield.
      Noteworthy, functionalizations of primary alcohols in the presence of secondary
      and tertiary alcohols proceed with excellent regioselectivity.

PMID- 20672811
TI  - Highly enantioselective hydrogenative desymmetrization of bicyclic imides leading
      to multiply functionalized chiral cyclic compounds.
AB  - Highly enantioselective hydrogenative desymmetrization of bicyclic imides has
      been developed with chiral Cp*Ru(PN) catalysts. The present hydrogenation
      directly provides stereochemically well-defined cyclic compounds with excellent
      enantiomeric exessses, which might otherwise require a detour to reach.

PMID- 20672812
TI  - Mechanistic study of the stereoselective polymerization of D,L-lactide using
      indium(III) halides.
AB  - We report the results of a comprehensive investigation of the recently discovered
      stereoselective and controlled polymerization of racemic lactide (D,L-LA) using
      an initiator prepared in situ from indium(III) chloride (InCl(3)), benzyl alcohol
      (BnOH), and triethylamine (NEt(3)). Linear relationships between number-average
      molecular weight (M(n)) and both monomer to alcohol concentration ratio and
      monomer conversion are consistent with a well-controlled polymerization. Studies
      on polymerization kinetics show the process to be first-order in [InCl(3)](0) and
      zero-order in both [BnOH](0) and [NEt(3)](0). The rate of D,L-LA conversion is
      also dependent on the indium(III) halide (i.e., t(1/2)(InCl(3)) approximately =
      43 min versus t(1/2)(InBr(3)) approximately = 7.5 h, 21 degrees C, CD(2)Cl(2),
      [D,L-LA](0)/[BnOH](0) approximately = 100, [D,L-LA](0) = 0.84 M,
      [InX(3)](0)/[BnOH](0) = 1) and lactide stereoisomer (i.e., k(obs)(D,L-LA)
      approximately = k(obs)(meso-LA) > k(obs)(L-LA)). A model system that polymerizes
      D,L-LA with the same high degree of stereoselectivity was developed using 3
      diethylamino-1-propanol (deapH) in lieu of BnOH and NEt(3). The product of the
      reaction of deapH with InCl(3) was identified as [InCl(3)(deapH)(H(2)O)](2) by
      elemental analysis, X-ray crystallography, and NMR and FTIR spectroscopies. An
      anhydrous version of the complex was also isolated when care was taken to avoid
      adventitious water, and was shown by pulsed gradient spin-echo (PGSE) NMR
      experiments to adopt a dinuclear structure in CD(2)Cl(2) solution under
      conditions identical to those used in its stereoselective polymerization of D,L
      LA. The combined data suggest that the initiating species for the
      InCl(3)/BnOH/NEt(3) system is similar to [InCl(3)(deapH)(H(2)O)](2) and of the
      type [InCl((3-n))(OBn)(n)](m). With this information we propose a mechanism that
      rationalizes the observed stereocontrol in D,L-LA polymerizations. Finally, in an
      exploration of the scope of the InCl(3)/BnOH/NEt(3) system, we found this system
      to be effective for the polymerization of other cyclic esters, including epsilon
      caprolactone and several substituted derivatives.

PMID- 20672813
TI  - Atom-economical synthesis of N-heterocycles via cascade inter-/intramolecular C-N
      bond-forming reactions catalyzed by Ti amides.
AB  - Direct and efficient catalytic reactions with excellent regioselectivity for the
      preparation of a series of substituted isoindoles, isoquinolines, and imidazoles
      are reported. Reaction of C(6)H(4)(2-CN)C[triple bond]C-R with an array of
      amines, catalyzed by 10 mol % of [sigma:eta(1):eta(5)
      (OCH(2))(Me(2)NCH(2))C(2)B(9)H(9)]Ti(NMe(2)) (1), gives a series of substituted
      isoindoles in very high yields. In a similar manner, interaction of C(6)H(4)(2
      CH(2)CN)C[triple bond]C-Ph with various kinds of amines affords a wide range of
      substituted isoquinolines. On the other hand, treatment of propargylamines
      (R'C[triple bond]CCH(2)NHR'') with nitriles in the presence of 10 mol % of 1
      produces a class of substituted imidazoles in high yields. A possible reaction
      mechanism is proposed, involving sequential inter- and intramolecular C-N bond
      formation via hydroamination/cyclization reaction of cyanoalkynes with amines or
      nitriles with propargylamines catalyzed by titanium amides.

PMID- 20672814
TI  - Detection of C-reactive protein in evanescent wave field using microparticle
      tracking velocimetry.
AB  - A new technique is developed to measure the nanoparticles' brownian motions by
      employing microparticle-tracking velocimetry (micro-PTV) in evanescent wave
      field, which can provide high signal-to-noise ratio images for analyzing
      nanoparticles' movements. This method enables real-time detection of C-reactive
      proteins (CRPs) during the rapid interaction between CRPs and anti-CRP-coated
      nanobeads as CRP concentrations are related to the nanobeads' brownian velocity
      in the equilibrium state. The smallest observable nanobeads with 185 nm were
      utilized in this experiment to detect CRP concentrations as low as 0.1 microg/mL
      even in a high-viscosity solution. Further, the dissociation constant, K(D), can
      be evaluated based on the experimental results.

PMID- 20672815
TI  - Structures of water molecules at solvent/silica interfaces.
AB  - The adsorption of water at solvent/silica interfaces was studied using IR-visible
      sum frequency generation (SFG) vibrational spectroscopy. We discovered a water
      layer between toluene and silica with no detectable free OHs. The water layer
      without free OHs showed resistance against further adsorption of water molecules.
      This "water-resistant" water surface was very stable at room temperature and did
      not become a regular water layer with free OH over a period of 12 h in water
      saturated toluene. However, this special structure of water was not observed at
      heptane/silica interfaces, at which free OHs were observed. The study indicates
      that interactions between solvents and water molecules can significantly change
      the interfacial water properties.

PMID- 20672816
TI  - Programmed assembly of peptide-functionalized gold nanoparticles on DNA
      templates.
AB  - We present a novel nanoparticle building block system based on the interactions
      between short synthetic oligonucleotides and peptides. Gold nanoparticles coated
      with DNA-binding peptides can be attached to self-organized oligonucleotide
      templates to formulate well-ordered structures of nanoparticles. By regulating
      the amount of DNA-binding peptide attached to the nanoparticle surface and using
      specifically designed oligonucleotides, the nanoparticle assembly can be
      controlled to form dimers, trimers, and adjustable-length nanoparticle chains as
      well as more complex structures.

PMID- 20672817
TI  - Role of interaction energies in the behavior of mixed surfactant systems: a
      lattice Monte Carlo simulation.
AB  - We have investigated micellization in systems containing two surfactant molecules
      with the same structure using a lattice Monte Carlo simulation method. For the
      binary systems containing two surfactants, we have varied the head-head
      interactions or tail-tail repulsions in order to mimic the nonideal behavior of
      mixed surfactant systems and to manipulate the net interactions between
      surfactant molecules. The simulation results indicate that interactions between
      headgroups or tailgroups have an effect on thermodynamic properties such as the
      mixed critical micelle concentration (cmc), distribution of aggregates, shape of
      the aggregates, and composition of the micelles formed. Moreover, we have
      compared the simulation results with estimates based on regular solution theory,
      a mean-field theory, to determine the applicability of this theory to the
      nonideal mixed surfactant systems. We have found that the simulation results
      agree reasonable well with regular solution theory for the systems with
      attractions between headgroups and repulsions between tailgroups. However, the
      large discrepancies observed for the systems with head-head repulsions could be
      attributed to the disregarding of the correlation effect on the interaction among
      surfactant molecules and the nonrandom mixing effect in the theory.

PMID- 20672818
TI  - Hydrogen bonds between nitrogen donors and the semiquinone in the Q(B) site of
      bacterial reaction centers.
AB  - Photosynthetic reaction centers from Rhodobacter sphaeroides have identical
      ubiquinone-10 molecules functioning as primary (Q(A)) and secondary (Q(B))
      electron acceptors. X-band 2D pulsed EPR spectroscopy, called HYSCORE, was
      applied to study the interaction of the Q(B) site semiquinone with nitrogens from
      the local protein environment in natural and (15)N uniformly labeled reactions
      centers. (14)N and (15)N HYSCORE spectra of the Q(B) semiquinone show the
      interaction with two nitrogens carrying transferred unpaired spin density.
      Quadrupole coupling constants estimated from (14)N HYSCORE spectra indicate them
      to be a protonated nitrogen of an imidazole residue and amide nitrogen of a
      peptide group. (15)N HYSCORE spectra allowed estimation of the isotropic and
      anisotropic couplings with these nitrogens. From these data, we calculated the
      unpaired spin density transferred onto 2s and 2p orbitals of nitrogen and
      analyzed the contribution of different factors to the anisotropic hyperfine
      tensors. The hyperfine coupling of other protein nitrogens with the semiquinone
      is weak (<0.1 MHz). These results clearly indicate that the Q(B) semiquinone
      forms hydrogen bonds with two nitrogens and provide quantitative characteristics
      of the hyperfine couplings with these nitrogens, which can be used in theoretical
      modeling of the Q(B) site. On the basis of the quadrupole coupling constant, one
      nitrogen can only be assigned to N(delta) of His-L190, consistent with all
      existing structures. However, we cannot specify between two candidates the
      residue corresponding to the second nitrogen. Further work employing
      multifrequency spectroscopic approaches or selective isotope labeling would be
      desirable for unambiguous assignment of this nitrogen.

PMID- 20672819
TI  - Identification of a hemerythrin-like domain in a P1B-type transport ATPase.
AB  - The P(1B)-type ATPases couple the energy of ATP hydrolysis to metal ion
      translocation across cell membranes. Important for prokaryotic metal resistance
      and essential metal distribution in eukaryotes, P(1B)-ATPases are divided into
      subclasses on the basis of their metal substrate specificities. Sequence analysis
      of putative P(1B-5)-ATPases, for which the substrate has not been identified, led
      to the discovery of a C-terminal soluble domain homologous to hemerythrin (Hr)
      proteins and domains. The Hr domain from the Acidothermus cellulolyticus P(1B-5)
      ATPase was cloned, expressed, and purified (P(1B-5)-Hr). P(1B-5)-Hr binds two
      iron ions per monomer and adopts a predominantly helical fold. Optical absorption
      features of the iron-loaded and azide-treated protein are consistent with
      features observed for other Hr proteins. Autoxidation to the met form is very
      rapid, as reported for other prokaryotic Hr domains. The presence of a diiron
      center was confirmed by electron paramagnetic resonance (EPR) and X-ray
      absorption spectroscopic (XAS) data. The occurrence of a Hr-like domain in a P
      type ATPase is unprecedented and suggests new regulatory mechanisms as well as an
      expanded function for Hr proteins in biology.

PMID- 20672820
TI  - Discovery of novel cyanodihydropyridines as potent mineralocorticoid receptor
      antagonists.
AB  - A new 1,4-dihydropyridine 5a, containing a cyano group at the C3 position, was
      recently reported to possess excellent mineralocorticoid receptor (MR) antagonist
      in vitro potency and no calcium channel-blocker (CCB) activity. In the present
      study, we report the structure-activity relationships of this novel series of
      cyano ester dihydropyridines that resulted in R6 substituted analogues with
      improved metabolic stability while maintaining excellent MR antagonist activity
      and selectivity against other nuclear receptors. Further structure optimization
      with the introduction of five-membered ring heterocycles at R6 resulted in
      compounds with excellent MR antagonist potency and a suitable pharmacokinetic
      profile. In vivo studies of a promising tool compound in the Dahl salt-sensitive
      rat model of hypertension showed similar blood pressure (BP) reduction as the
      steroidal MR antagonist eplerenone, providing proof-of-concept (POC) for a
      nonsteroidal, orally efficacious MR antagonist.

PMID- 20672822
TI  - Discovery of (3S,3aR)-2-(3-chloro-4-cyanophenyl)-3-cyclopentyl-3,3a,4,5
      tetrahydro-2H-benzo[g]indazole-7-carboxylic acid (PF-3882845), an orally
      efficacious mineralocorticoid receptor (MR) antagonist for hypertension and
      nephropathy.
AB  - We have discovered a novel class of nonsteroidal pyrazoline antagonists of the
      mineralocorticoid receptor (MR) that show excellent potency and selectivity
      against other nuclear receptors. Early analogues were poorly soluble and had a
      propensity to inhibit the hERG channel. Remarkably, both of these challenges were
      overcome by incorporation of a single carboxylate moiety. Structural modification
      of carboxylate-containing lead R-4g with a wide range of substituents at each
      position of the pyrazoline ring resulted in R-12o, which shows excellent activity
      against MR and reasonable pharmacokinetic profile. Introduction of conformational
      restriction led to a novel series characterized by exquisite potency and
      favorable steroid receptor selectivity and pharmacokinetic profile. Oral dosing
      of 3S,3aR-27d (PF-3882845) in the Dahl salt sensitive preclinical model of salt
      induced hypertension and nephropathy showed blood pressure attenuation
      significantly greater than that with eplerenone, reduction in urinary albumin,
      and renal protection. As a result of these findings, 3S,3aR-27d was advanced to
      clinical studies.

PMID- 20672823
TI  - A highly selective low-background fluorescent imaging agent for nitric oxide.
AB  - We introduce a novel sensing mechanism for nitric oxide (NO) detection with a
      particular easily synthesized embodiment (NO(550)), which displays a rapid and
      linear response to NO with a red-shifted 1500-fold turn-on signal from a dark
      background. Excellent selectivity was observed against other reactive
      oxygen/nitrogen species, pH, and various substances that interfere with existing
      probes. NO(550) crosses cell membranes but not nuclear membranes and is suitable
      for both intra- and extracellular NO quantifications. Good cytocompatibility was
      found during in vitro studies with two different cell lines. The high
      specificity, dark background, facile synthesis, and low pH dependence make
      NO(550) a superior probe for NO detection when used as an imaging agent.

PMID- 20672824
TI  - Experimental studies on anisotropic thermoelectric properties and structures of n
      type Bi2Te2.7Se0.3.
AB  - The peak dimensionless thermoelectric figure-of-merit (ZT) of Bi(2)Te(3)-based n
      type single crystals is about 0.85 in the ab plane at room temperature, which has
      not been improved over the last 50 years due to the high thermal conductivity of
      1.65 W m(-1) K(-1) even though the power factor is 47 x 10(-4) W m(-1) K(-2). In
      samples with random grain orientations, we found that the thermal conductivity
      can be decreased by making grain size smaller through ball milling and hot
      pressing, but the power factor decreased with a similar percentage, resulting in
      no gain in ZT. Reorienting the ab planes of the small crystals by repressing the
      as-pressed samples enhanced the peak ZT from 0.85 to 1.04 at about 125 degrees C,
      a 22% improvement, mainly due to the more increase on power factor than on
      thermal conductivity. Further improvement is expected when the ab plane of most
      of the small crystals is reoriented to the direction perpendicular to the press
      direction and grains are made even smaller.

PMID- 20672826
TI  - Real space mapping of Li-ion transport in amorphous Si anodes with nanometer
      resolution.
AB  - The electrical bias driven Li-ion motion in silicon anode materials in thin film
      battery heterostructures is investigated using electrochemical strain microscopy
      (ESM), which is a newly developed scanning probe microscopy based
      characterization method. ESM utilizes the intrinsic link between bias-controlled
      Li-ion concentration and molar volume of electrode materials, providing the
      capability for studies on the sub-20 nm scale, and allows the relationship
      between Li-ion flow and microstructure to be established. The evolution of Li-ion
      transport during the battery charging is directly observed.

PMID- 20672825
TI  - Structure-activity relationships for a novel series of citalopram (1-(3
      (dimethylamino)propyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5
      carbonitrile) analogues at monoamine transporters.
AB  - (+/-)-Citalopram (1, 1-(3-(dimethylamino)propyl)-1-(4-fluorophenyl)-1,3
      dihydroisobenzofuran-5-carbonitrile), and its eutomer, escitalopram (S-(+)-1) are
      selective serotonin reuptake inhibitors (SSRIs) that are used clinically to treat
      anxiety and depression. To further explore structure-activity relationships at
      the serotonin transporter (SERT), a series of (+/-)-4- and 5-substituted
      citalopram analogues were designed, synthesized, and evaluated for binding at the
      SERT, dopamine transporter (DAT) and norepinephrine transporter (NET) in native
      rodent tissue. Many of these analogues showed high SERT binding affinities (Ki=1
      40 nM) and selectivities over both NET and DAT. Selected enantiomeric pairs of
      analogues were synthesized and both retained enantioselectivity as with S- and R
      1, wherein S>R at the SERT. In addition, the enantiomeric pairs of 1 and 5 were
      tested for binding at the homologous bacterial leucine transporter (LeuT),
      wherein low affinities and the absence of enantioselectivity suggested
      distinctive binding sites for these compounds at SERT as compared to LeuT. These
      novel ligands will provide molecular tools to elucidate drug-protein interactions
      at the SERT and to relate those to behavioral actions in vivo.

PMID- 20672827
TI  - Sensitive method for the kinetic measurement of trace species in liquids using
      cavity enhanced absorption spectroscopy with broad bandwidth supercontinuum
      radiation.
AB  - A novel spectrometer for the rapid and sensitive detection of liquid phase
      analytes at trace concentrations is presented. Broad bandwidth supercontinuum
      radiation was coupled into a linear optical cavity incorporating an intracavity
      liquid-sample cuvette. Cavity enhanced absorption spectra of trace species
      covering more than 300 nm were acquired on time scales of milliseconds. Single
      shot acquisition times of 10-50 ms are demonstrated here. The effective
      absorption path length exceeds 2 m in sample volumes measuring 2.7 mL. A key
      feature of the instrument is that it can be calibrated using cavity ring-down
      spectroscopy without the requirement of changing the optical alignment. The
      sensitivity of the instrument is exemplified by measurements of trace
      concentrations of dye molecules and nickel sulfate dissolved in water. A minimum
      detectable absorption coefficient of 9.1 x 10(-7) cm(-1) Hz(-1/2) at 550 nm was
      obtained. The capability to capture broad bandwidth absorption spectra on short
      time scales permits kinetic studies of liquid phase reactions. We demonstrate
      this by recording the oscillatory behavior of a Belousov-Zhabotinsky reaction.

PMID- 20672828
TI  - Ion beam analysis and PD-MS as new analytical tools for quality control of
      pharmaceuticals: comparative study from fluphenazine in solid dosage forms.
AB  - In order to evaluate the potential of accelerator based analytical techniques
      ((particle induced X-ray emission (PIXE), particle induced gamma-ray emission
      (PIGE), and particle desorption mass spectrometry (PD-MS)) for the analysis of
      commercial pharmaceutical products in their solid dosage form, the fluphenazine
      drug has been taken as a representative example. It is demonstrated that PIXE and
      PIGE are by far the best choice for quantification of the active ingredient (AI)
      (certification with 7% precision) from the reactions induced on its specific
      heteroatoms fluorine and sulfur using pellets made from original tablets. Since
      heteroatoms cannot be present in all types of drugs, the PD-MS technique, which
      makes easily the distinction between AI(s) and excipients, has been evaluated for
      the same material. It is shown that the quantification of AI is obtained via the
      detection of its protonated molecule. However, calibration curves have to be made
      from the secondary ion yield variations since matrix effects of various nature
      are characteristics of such mixtures of heterogeneous materials (including
      deposits from soluble components). From the analysis of solid tablets, (either
      transformed into pellets and even as received), it is strongly suggested that the
      physical state of the grains in the mixture is a crucial parameter in the ion
      emission and accordingly for the calibration curves. As a result of our specific
      (but not optimized) conditions the resulting precision is <17% with an almost
      linear range extending from 0.04 to 7.87 mg of AI in a tablet made under the
      manufacturer conditions (the commercial drug product is labeled at 5 mg).

PMID- 20672829
TI  - Chemical speciation of individual airborne particles by the combined use of
      quantitative energy-dispersive electron probe X-ray microanalysis and attenuated
      total reflection Fourier transform-infrared imaging techniques.
AB  - In our previous work, it was demonstrated that the combined use of attenuated
      total reflectance (ATR) FT-IR imaging and quantitative energy-dispersive electron
      probe X-ray microanalysis (ED-EPMA), named low-Z particle EPMA, had the potential
      for characterization of individual aerosol particles. Additionally, the
      speciation of individual mineral particles was performed on a single particle
      level by the combined use of the two techniques, demonstrating that simultaneous
      use of the two single particle analytical techniques is powerful for the detailed
      characterization of externally heterogeneous mineral particle samples and has
      great potential for characterization of atmospheric mineral dust aerosols. These
      single particle analytical techniques provide complementary information on the
      physicochemical characteristics of the same individual particles, such as low-Z
      particle EPMA on morphology and elemental concentrations and the ATR-FT-IR
      imaging on molecular species, crystal structures, functional groups, and physical
      states. In this work, this analytical methodology was applied to characterize an
      atmospheric aerosol sample collected in Incheon, Korea. Overall, 118 individual
      particles were observed to be primarily NaNO(3)-containing, Ca- and/or Mg
      containing, silicate, and carbonaceous particles, although internal mixing states
      of the individual particles proved complicated. This work demonstrates that more
      detailed physiochemical properties of individual airborne particles can be
      obtained using this approach than when either the low-Z particle EPMA or ATR-FT
      IR imaging technique is used alone.

PMID- 20672830
TI  - Improved mechanical stability of dried collagen membrane after metal
      infiltration.
AB  - A few percent of transition metals impregnated inside some biological organisms
      in nature remarkably improve such organisms' mechanical stability. Although the
      lure to emulate them for development of new biomimetic structural materials has
      been great, the practical advances have been rare because of the lack of proper
      synthetic approaches. Multiple pulsed vapor phase infiltration proved successful
      for the preparation of such transition metal impregnated materials with highly
      improved mechanical stability. The artificially infiltrated metals (Al, Ti, or
      Zn) from gas phase lead to around 3 times increase of toughness (in terms of
      breaking energy) of natural collagen in a dried state. In addition, the
      infiltrated metals apparently induce considerable crystallographic changes in the
      natural collagen structures. This infiltration approach can be used as guide for
      the synthesis of bioinspired structural materials related to metal infiltration.

PMID- 20672831
TI  - Probing nanoparticle--protein interaction by capillary electrophoresis.
AB  - Understanding nanoparticle-protein interaction could help in promoting
      applications of nanoparticles in the biomedical fields and reducing/preventing
      possible adverse effects to the biological systems caused by nanoparticles.
      Quantitative measurement of the biophysical parameters of nanoparticle-protein
      interaction will improve such understanding, which could be conveniently
      performed by capillary electrophoresis (CE) as demonstrated in the present study.
      Two interaction situations were identified. Stable nanoparticle-protein complexes
      were resolved from the free nanoparticles and the proteins by capillary zone
      electrophoresis (CZE). Transient complexes with fast association/dissociation
      rates showed distinct mobility change from the free nanoparticles in affinity
      capillary electrophoresis (ACE). Interactions of bovine serum albumin (BSA) with
      the Fe(3)O(4) nanoparticles (average diameters of 8 and 10 nm) and with the Au
      nanoparticles (average diameters of 5 and 10 nm) displayed slow and fast binding
      kinetics, respectively. Using the Hill equation, we could calculate the
      dissociation constants (K(D)) and cooperativity coefficients (n). Impacts on
      nanoparticle-protein interaction from the physicochemical properties of
      nanoparticles and the incubation buffer were evaluated on the basis of the K(D)
      and n values to interpret the interaction driving forces. Our study demonstrated
      the high simplicity and flexibility of CE in probing the interaction of proteins
      with diverse particles. The separation power of CE should also facilitate studies
      of the multicomponent interaction systems for investigating how adsorption onto
      nanoparticles could affect the protein-protein or protein-small molecule
      interactions.

PMID- 20672832
TI  - Born-Oppenheimer molecular dynamics on the H(2)S + NO(3) reaction in the presence
      and absence of water: the kinetic isotope effect.
AB  - The chemical mechanism of the H(2)S + NO(3) reaction in the absence and presence
      of water molecules was investigated using the Born-Oppenheimer molecular
      dynamics. These calculations were performed to gain insight into the underlying
      chemical mechanism and to evaluate the kinetic isotope effect in the H(2)S +
      NO(3) and D(2)S + NO(3) reactions. When H(2)O interacts with NO(3), the rate
      coefficient of the H(2)S + NO(3) reaction is smaller than that for H(2)O
      interacting with H(2)S. Deuterium generally decreases the rate when D(2)O
      interacts with D(2)S but has no effect when D(2)O interacting with NO(3). When
      H(2)O or D(2)O interacts with NO(3), the yields are larger compared to those for
      the reactions (H(2)O)H(2)S + NO(3) and (D(2)O)H(2)S + NO(3). Furthermore, the
      average reaction times of the reactions H(2)S + NO(3)(H(2)O) and H(2)S +
      NO(3)(D(2)O) are shorter than those when H(2)O or D(2)O interacts with H(2)S. The
      (H(2)O)H(2)S + NO(3) reaction may occur via two possible pathways: the non-water
      assisted and water-assisted hydrogen abstraction mechanisms. However, the H(2)S +
      NO(3)(H(2)O) reaction only happens via the non-water-assisted mechanism.

PMID- 20672833
TI  - Crystallographic evidence of a base-free uranium(IV) terminal oxo species.
AB  - The uranium(IV) terminal oxo species Tp*(2)U(O) has been synthesized by oxygen
      atom transfer from pyridine-N-oxide to Tp*(2)U(2,2'-bipyridine), a trivalent
      uranium species with a monoanionic bipyridine ligand. Full characterization of
      the oxo species using (1)H NMR and IR spectroscopies, X-ray crystallography, and
      computational studies was performed.

PMID- 20672834
TI  - Highly diastereo- and enantioselective synthesis of monodifferentiated syn-1,2
      diol derivatives through asymmetric transfer hydrogenation via dynamic kinetic
      resolution.
AB  - The first enantio- and diastereoselective approach to alpha-alkoxy-substituted
      syn-beta-hydroxyesters through highly efficient catalytic asymmetric transfer
      hydrogenation via dynamic kinetic resolution reactions from the corresponding
      racemic beta-ketoesters is described. In this atom-economical process, two
      contiguous stereogenic centers are generated simultaneously with an excellent
      diastereoselectivity (up to 99/1) and enantioselectivity (up to 99%), allowing a
      rapid access to a wide variety of aromatic and heteroaromatic monodifferentiated
      syn-1,2-diols.

PMID- 20672835
TI  - Bright sky-blue phosphorescence of [n-Bu4N][Pt(4,6-dFppy)(CN)2]: synthesis,
      crystal structure, and detailed photophysical studies.
AB  - This work describes the synthesis, crystal structure, and detailed photophysical
      studies of [n-Bu(4)N][Pt(4,6-dFppy)(CN)(2)] (n-Bu = n-butyl, 4,6-dFppy = (4',6'
      difluorophenyl)pyridinate). The material can easily be prepared in high yield and
      purity by the reaction of [Pt(4,6-dFppy)(H-4,6-dFppy)Cl], [n-Bu(4)N]Cl, and KCN
      in CH(2)Cl(2). Because of the bulky counterion [n-Bu(4)N](+), Pt-Pt interactions,
      which frequently lead to aggregate formation, are suppressed in the solid state.
      Thus, monomer emission is observed. The phosphorescence quantum yield of the neat
      powder amounts to phi(PL) = 60% at ambient temperature and decays with 19 micros.
      In tetrahydrofuran (THF) solution, on the other hand, the emission decay time is
      with 0.26 micros distinctly shorter, and the quantum yield is very low. By means
      of emission decay time studies in frozen THF and investigations of the highly
      resolved single crystal emission at 1.2 K, we can assign the emitting T(1) state
      of the compound as being largely of ligand centered ((3)LC, (3)pi pi*) character.
      The observed differences of the emission properties of the neat powder compared
      to the fluid solution are rationalized with an energy stabilization of quenching
      dd* states in solution because of molecular distortions and/or bond elongations.

PMID- 20672836
TI  - Properties of double-stranded oligonucleotides modified with lipophilic
      substituents.
AB  - We have synthesized a series of short, self-complementary oligonucleotide
      sequences modified at their 5'- and/or 3'- termini with a lipophilic dodecane
      (C12); these systems serve as models to assess the biophysical properties of
      double-stranded DNA (dsDNA) equipped with potentially stabilizing lipophilic
      substituents. Addition of C12 to the 5'-termini of self-complementary 10
      nucleotide sequences increased their duplex melting temperatures (T(m)) by
      approximately 4-8 degrees C over their corresponding unmodified sequences. C12
      functionalities added to both the 3'- and 5'-termini increased T(m) values by
      approximately 10-12 degrees C. The observed increases in T(m) correlated with
      greater duplex stabilities as determined by the free energy values (DeltaG)
      derived from T(m) plots. There is a greater degree of stabilization when C12 is
      positioned with a C.G base pair at the termini, and the stabilizing effect of
      lipophilic groups far exceeds the effect seen in adding an additional base pair
      to both ends of DNA. Stable, short dsDNA sequences are of potential interest in
      the development of transcription factor decoy oligonucleotides as possible
      therapeutic agents and/or biological tools. These results suggest that the
      stability of short dsDNA sequences are improved by lipophilic substituents and
      can be used as the basis for the design of dsDNAs with improved biological
      stabilities and function under physiological conditions.

PMID- 20672837
TI  - Characterization of a recombinant form of annexin VI for detection of apoptosis.
AB  - We developed a recombinant form of human annexin VI called annexin VI-601 (M(r)
      76,224) with the N-terminal extension of Ala-Gly-Gly-Cys-Gly-His to allow ready
      attachment of fluorescent or radioactive labels. The protein was produced by
      expression in E. coli and was purified by calcium-dependent membrane binding,
      anion-exchange chromatography, and heparin-Sepharose affinity chromatography. The
      protein could be readily labeled with iodoacetamidofluorescein and with (99m)Tc.
      The protein bound with high affinity to PS-containing phospholipid vesicles and
      to erythrocytes with exposed phosphatidylserine. Fluorescent annexin VI-601
      readily detected apoptosis of Jurkat cells by flow cytometry at much lower
      calcium concentrations than those required for equivalent detection by annexin V.
      In vivo administration of radiolabeled protein showed that blood clearance was
      much slower than annexin V. In conclusion, annexin VI may have advantages over
      annexin V in certain situations for both in vitro and in vivo detection of
      apoptosis and therapeutic targeting of PS due to its lower calcium requirement
      for membrane binding and its higher molecular weight.

PMID- 20672838
TI  - Evaluation of the in vivo anti-inflammatory effects of extracts from Pyrus
      bretschneideri Rehd.
AB  - Pyrus bretschneideri Rehd., as a pharmaceutical supplement, is widely used in
      northern China to treat respiratory diseases. Our previous studies showed the
      ethanol extract of P. bretschneideri had significant anti-inflammatory activity.
      To isolate and identify the active ingredients, the ethanol extract was separated
      into petroleum ether, ethyl acetate, n-butanol, and aqueous fractions. The
      bioactivity of each fraction was investigated using an in vivo model. Results
      showed that the ethyl acetate fraction exhibited the strongest anti-inflammatory
      effect. Subsequently, this fraction was subjected to separation and purification
      using silica gel column chromatography, C18-ODS, and recrystallization, leading
      to two sterols and two triterpenes, which were identified as beta-sitosterol,
      daucosterol, oleanolic acid, and ursolic acid. Moreover, all of the isolated
      compounds could significantly inhibit the ear edema induced by xylene. These
      results indicated that P. bretschneideri had good anti-inflammatory effects and
      the constituents beta-sitosterol, daucosterol, oleanolic acid, and ursolic acid
      might well account for it.

PMID- 20672839
TI  - Evaluation of reference genes for quantitative polymerase chain reaction across
      life cycle stages and tissue types of Tribolium castaneum.
AB  - The genome of the genetic model for coleopteran insects, Tribolium castaneum, is
      now available for downstream applications. To facilitate gene expression studies
      in T. castaneum, genes were evaluated for suitability as normalizers in
      comparisons across tissues and/or developmental stages. In less diverse samples,
      such as comparisons within developmental stages or tissue only, normalizers for
      mRNA were more stable and consistent. Overall, the genes for ribosomal proteins
      rps6, rpl13a, rps3, and rps18 were the most stable normalizers for broad scale
      gene expression analysis in T. castaneum. However, their stability ranking was
      dependent upon the instrument as well as the analysis program. These data
      emphasize the need to optimize normalizers used in all real-time polymerase chain
      reaction experiments specifically for the experimental conditions and
      thermocycler and to carefully evaluate data generated by computational
      algorithms.

PMID- 20672841
TI  - Falcipain inhibitors: optimization studies of the 2-pyrimidinecarbonitrile lead
      series.
AB  - Falcipain-2 and falcipain-3 are papain-family cysteine proteases of the malaria
      parasite Plasmodium falciparum that are responsible for host hemoglobin
      hydrolysis to provide amino acids for parasite protein synthesis. Different
      heteroarylnitrile derivatives were studied as potential falcipain inhibitors and
      therefore potential antiparasitic lead compounds, with the 5-substituted-2
      cyanopyrimidine chemical class emerging as the most potent and promising lead
      series. Through a sequential lead optimization process considering the different
      positions present in the initial scaffold, nanomolar and subnanomolar inhibitors
      at falcipains 2 and 3 were identified, with activity against cultured parasites
      in the micromolar range. Introduction of protonable amines within lead molecules
      led to marked improvements of up to 1000 times in activity against cultured
      parasites without noteworthy alterations in other SAR tendencies. Optimized
      compounds presented enzymatic activities in the picomolar to low nanomolar range
      and antiparasitic activities in the low nanomolar range.

PMID- 20672840
TI  - Strategies for recognition of stem-loop RNA structures by synthetic ligands:
      application to the HIV-1 frameshift stimulatory sequence.
AB  - Production of the Gag-Pol polyprotein in human immunodeficiency virus (HIV)
      requires a -1 ribosomal frameshift, which is directed by a highly conserved RNA
      stem-loop. Building on our discovery of a set of disulfide-containing peptides
      that bind this RNA, we describe medicinal chemistry efforts designed to begin to
      understand the structure-activity relationships and RNA sequence-selectivity
      relationships associated with these compounds. Additionally, we have prepared
      analogues incorporating an olefin or saturated hydrocarbon bioisostere of the
      disulfide moiety, as a first step toward enhancing biostability. The olefin
      containing compounds exhibit affinity comparable to the lead disulfide and,
      importantly, have no discernible toxicity when incubated with human fibroblasts
      at concentrations up to 1 mM.

PMID- 20672842
TI  - Sole and stable RNA duplexes of G-rich sequences located in the 5'-untranslated
      region of protooncogenes.
AB  - Guanine- (G-) rich nucleic acid sequences can form four-stranded structures
      called G-quadruplexes. It is widely held that the formation of a G-quadruplex in
      RNA is more feasible than in DNA because of the lack of a complementary strand in
      mRNA. Here, we analyzed sequences of 5'-untranslated regions of protooncogenes
      and surprisingly found that these regions showed an enrichment of not only
      guanine (G) but also cytosine (C) nucleotides. Since neighboring cytosine- (C-)
      rich regions can affect the formation and stability of a G-quadruplex structure,
      we further investigated the properties of DNA and RNA structures of G-rich and GC
      rich regions. We selected typical GC-rich RNA sequences from protooncogenes and
      corresponding DNA sequences and investigated their structures. It was found that
      the GC-rich RNA sequences formed stable A-form duplexes as their major structure
      independent of the surrounding conditions, including the presence of different
      cations (Na(+), K(+), or Li(+)) or molecular crowding with 40 wt % poly(ethylene
      glycol) with an average molecular mass of 200 Da although there are a few
      exceptions in which only a combination of K(+) and molecular crowding induced a G
      quadruplex structure of an extremely G-rich RNA sequence. In contrast, structural
      polymorphisms involving duplexes, G-quadruplexes, and i-motifs were observed for
      GC-rich DNA sequences depending on the surrounding factors. These results
      demonstrate the considerable structural and functional differences in GC-rich
      sequences of the genome (DNA) and transcriptosome (mRNA) with respect to the
      nucleic acid backbone. Moreover, it was suggested that structural study for a G
      rich RNA sequence should be carried out under cell-mimicking condition where K(+)
      and crowding cosolutes exist.

PMID- 20672843
TI  - Zero kinetic energy spectroscopy: mass-analyzed threshold ionization spectra of
      chromium sandwich complexes with alkylbenzenes, (eta(6)-RPh)(2)Cr (R = Me, Et, i
      Pr, t-Bu).
AB  - For over 25 years zero kinetic energy (ZEKE) spectroscopy has yielded a rich
      foundation of high-resolution results of molecular ions. This was based on the
      discovery in the late 60's of long-lived ion states throughout the ionization
      continuum of molecular ions. Here, an example is chosen from another fundamental
      system pioneered at this university. The mass-analyzed threshold ionization
      (MATI) spectra of jet-cooled chromium bisarene complexes (eta(6)-RPh)(2)Cr (R =
      Me (1), Et (2), i-Pr (3), and t-Bu (4)) have been measured and interpreted on the
      basis of DFT calculations. The MATI spectra of complexes 1 and 2 appear to reveal
      features arising from ionizations of the isomers formed by the rotation of one
      arene ring relative to the other. The 1 and 2 MATI spectra show two intense peaks
      corresponding to the 0(0)(0) ionizations with inverse intensity ratios. As
      indicated by the DFT calculations, the intensity ratio change on going from 1 to
      2 results from different isomers contributing to each MATI peak. The ionization
      energies corresponding to the 0(0)(0) peaks are 42746 +/- 5 and 42809 +/- 5 cm(
      1) for compound 1 and 42379 +/- 5 and 42463 +/- 5 cm(-1) for complex 2. The 1 and
      2 spectra show also the weaker features representing transitions to the
      vibrationally excited cationic levels, the signals of individual rotamers being
      detected and assigned on the basis of calculated vibrational frequencies. The
      MATI spectra of compounds 3 and 4 reveal only one strong peak because of close
      ionization potentials of the isomers contributing to the MATI signal. The 3 and 4
      ionization energies are 42104 +/- 5 and 41917 +/- 5 cm(-1), respectively. The
      precise values of ionization energies obtained from the MATI spectra reveal a
      nonlinear dependence of the IE on the number of Me groups in the alkyl
      substituents of (eta(6)-RPh)(2)Cr. This can be explained by an increase in the
      molecular zero point energies on methylation of the substituents.

PMID- 20672844
TI  - Metal organic frameworks assembled from Y(III), Na(I), and chiral flexible
      achiral rigid dicarboxylates.
AB  - New chiral metal organic frameworks, assembled from Y(III), Na(I), and chiral
      flexible-achiral rigid dicarboxylate ligands, formulated as
      [NaY(Tart)(BDC)(H(2)O)(2)] (1) and [NaY(Tart)(biBDC)(H(2)O)(2)] (2) (H(2)Tart =
      Tartaric acid; H(2)BDC = Terephthalic acid; H(2)biBDC = Biphenyl-4,4'
      dicarboxylic acid), were obtained as single phases under hydrothermal conditions.
      Their structures were solved by single-crystal X-ray diffraction (XRD), and
      characterized by (13)C CPMAS NMR, thermal analyses (thermogravimetry-mass
      spectrometry (TG-MS) and differential scanning calorimetry (DSC)), and X-ray
      thermodiffractometry. Both compounds crystallize in the orthorhombic chiral space
      group C222(1) with a = 6.8854(2) A, b = 30.3859(7) A, c = 7.4741(2) A for 1, and
      a = 6.8531(2) A, b = 39.0426(8) A, c = 7.4976(2) A for 2. 1 and 2 are layered
      structures whose three-dimensional stability is ensured by strong hydrogen bond
      interactions. The dehydration of both compounds is accompanied by phase
      transformation, while the spontaneous rehydration process is characterized by
      different kinetics, fast in the case of 1 and slow for 2.

PMID- 20672845
TI  - Theoretical study of the gas-phase reactions of iodine atoms ((2)P(3/2)) with
      H(2), H(2)O, HI, and OH.
AB  - The rate constants of the reactions of iodine atoms with H(2), H(2)O, HI, and OH
      have been estimated using 39, 21, 13, and 39 different levels of theory,
      respectively, and have been compared to the available literature values over the
      temperature range of 250-2500 K. The aim of this methodological work is to
      demonstrate that standard theoretical methods are adequate to obtain quantitative
      rate constants for the reactions involving iodine-containing species. Geometry
      optimizations and vibrational frequency calculations are performed using three
      methods (MP2, MPW1K, and BHandHLYP) combined with three basis sets (cc-pVTZ, cc
      pVQZ, and 6-311G(d,p)). Single-point energy calculations are performed with the
      highly correlated ab initio coupled cluster method in the space of single,
      double, and triple (pertubatively) electron excitations CCSD(T) using the cc-pVnZ
      (n = T, Q, and 5), aug-cc-pVnZ (n = T, Q, and 5), 6-311G(d,p), 6-311+G(3df,2p),
      and 6-311++G(3df,3pd) basis sets. Canonical transition state theory with a simple
      Wigner tunneling correction is used to predict the rate constants as a function
      of temperature. CCSD(T)/cc-pVnZ//MP2/cc-pVTZ (n = T and Q), CCSD(T)/6
      311+G(3df,2p)//MP2/6-311G(d,p), and CCSD(T)/6-311++G(3df,3pd)//MP2/6-311G(d,p)
      levels of theory provide accurate kinetic rate constants when compared to
      available literature data. The use of the CCSD(T)/cc-pVQZ//MP2/cc-pVTZ and
      CCSD(T)/6-311++G(3df,3pd) levels of theory allows one to obtain a better
      agreement with the literature data for all reactions with the exception of the I
      + H(2) reaction R(1) . This computational procedure has been also used to predict
      rate constants for some reactions where no available experimental data exist. The
      use of quantum chemistry tools could be therefore extended to other elements and
      next applied to develop kinetic networks involving various fission products,
      steam, and hydrogen in the absence of literature data. The final objective is to
      implement the kinetics of gaseous reactions in the ASTEC (Accident Source Term
      Evaluation Code) code to improve speciation of fission transport, which can be
      transported along the Reactor Coolant System (RCS) of a Pressurized Water Reactor
      (PWR) in case of a severe accident.

PMID- 20672846
TI  - Surface orientation of phenyl groups in poly(sodium 4-styrenesulfonate) and in
      poly(sodium 4-styrenesulfonate):poly(3,4-ethylenedioxythiophene) mixture examined
      by sum frequency generation vibrational spectroscopy.
AB  - Sum frequency generation (SFG) vibrational spectroscopy was used to investigate
      the surface phenyl ring orientations of spin-coated poly(sodium 4
      styrenesulfonate) (PSSNa) and of PSSNa in the spin-coated polymer material
      Baytron P. Baytron P is a commercially available conducting polymer suspension
      with poly(3,4-ethylenedioxythiophene) (PEDOT) and PSSNa in water, which is widely
      used in organic electronic devices. SFG spectra collected using different
      polarization combinations showed that the twist angles for the phenyl groups on
      the spin-coated PSSNa and Baytron P surfaces were not random; therefore, both the
      twist and tilt angles needed to be deduced in order to determine their respective
      phenyl group orientations. Results indicated that on the PSSNa surface, the para
      substituted phenyl ring has a tilt angle of 47.5 degrees +/- 5.3 degrees and a
      twist angle of 58.8 degrees +/- 8.2 degrees. The tilt and twist angles, 48.2
      degrees +/- 3.6 degrees and 65.2 degrees +/- 4.0 degrees, respectively, were
      determined for the Baytron P phenyl ring, which were not very different from
      those of PSSNa phenyl groups on the surface.

PMID- 20672847
TI  - Producing high-density high-molecular-weight polymer brushes by a "grafting to"
      method from a concentrated homopolymer solution.
AB  - Here, a new procedure and method are presented for the production of highly
      grafted polymer brushes. Thiol-terminated polyethylene oxide (PEO-SH) of
      molecular weight (M(w)) 20,000 (20k) is grafted to a gold surface from highly
      concentrated aqueous solutions of nonthiolated polyethylene oxide homopolymer.
      The M(w) and volume fraction of the homopolymer solution are varied in order to
      control the grafting density of the resulting PEO-SH brush. As a result, 20k M(w)
      PEO-SH brushes with grafting densities up to 0.3 chains/nm(2) are achieved, as
      determined by ellipsometry. Highly concentrated homopolymer solutions of volume
      fraction greater than approximately 12% and M(w) greater than approximately 938
      produce near-ideal solvent conditions for the 20k M(w) PEO-SH chains; we have
      found that this facilitates the achievement of higher grafting densities of end
      functionalized polymer brushes than would be possible from simple solutions. We
      propose this as a suitable method for applications where the grafting density of
      a brush surface must be accurately varied and controlled consistently. The effect
      of chemisorption time and cleaning procedure on the resulting brush grafting
      density are also explored.

PMID- 20672848
TI  - IgG fc N-glycosylation changes in Lambert-Eaton myasthenic syndrome and
      myasthenia gravis.
AB  - N-glycosylation of the immunoglobulin Fc moiety influences its biological
      activity by, for example, modulating the interaction with Fc receptors. Changes
      in IgG glycosylation have been found to be associated with various inflammatory
      diseases. Here we evaluated for the first time IgG Fc N-glycosylation changes in
      well-defined antibody-mediated autoimmune diseases, that is, the neurological
      disorders Lambert-Eaton myasthenic syndrome and myasthenia gravis, with
      antibodies to muscle nicotinic acetylcholine receptors or muscle-specific kinase.
      IgGs were purified from serum or plasma by protein A affinity chromatography and
      digested with trypsin. Glycopeptides were purified and analyzed by MALDI-FTICR
      MS. Glycoform distributions of both IgG1 and IgG2 were determined for 229
      patients and 56 controls. We observed an overall age and sex dependency of IgG Fc
      N-glycosylation, which was in accordance with literature. All three disease
      groups showed lower levels of IgG2 galactosylation compared to controls. In
      addition, LEMS patients showed lower IgG1 galactosylation. Notably, the
      galactosylation differences were not paralleled by a difference in IgG
      sialylation. Moreover, the level of IgG core-fucosylation and bisecting N
      acetylglucosamine were evaluated. The control and disease groups revealed similar
      levels of IgG Fc core-fucosylation. Interestingly, LEMS patients below 50 years
      showed elevated levels of bisecting N-acetylglucosamine on IgG1 and IgG2,
      demonstrating for the first time the link of changes in the level of bisecting N
      acetylglucosamine with disease.

PMID- 20672849
TI  - Synthesis, structure determination, and biological evaluation of destruxin E.
AB  - The total synthesis of destruxin E (1) has been achieved for the first time, and
      the stereochemistry of its chiral center at the epoxide has been determined to be
      (S). The cyclization precursor 3a was synthesized by solid-phase peptide
      synthesis. Macrolactonization of 3a utilizing MNBA-DMAPO, followed by formation
      of the epoxide, then furnished destruxin E. Its diastereomer, epi-destruxin E
      (2), was also synthesized in the same manner. Furthermore, the biological
      evaluation indicated that destruxin E exhibits V-ATPase inhibitory activity 10
      fold greater than that of epi-destruxin E.

PMID- 20672850
TI  - Surface functional polymers by post-polymerization modification using
      diarylcarbenes: introduction, release and regeneration of hydrogen peroxide and
      bactericidal activity.
AB  - Functionalized diarylcarbenes are excellent reactive intermediates suitable for
      the direct surface modification of organic polymers, and these may be used to
      introduce urea and thiourea functions onto polystyrene at loading levels of up to
      2.3 x 10(13) molecules/cm(2). These functions are capable of the reversible
      binding and release of peroxide at loading levels of up to 0.6 mmol/g and give
      polymers that display biocidal activity against a spectrum of gram-positive and
      gram-negative bacteria.

PMID- 20672851
TI  - New amphiphilic carriers forming pH-sensitive nanoparticles for nucleic acid
      delivery.
AB  - Amphiphilic lipids are promising for efficient intracellular delivery of nucleic
      acids. In this study, two new amphiphilic carriers, EKHCO and EHHKCO, were
      designed and synthesized as multifunctional carriers for efficient intracellular
      delivery of nucleic acids. The critical micelle concentrations of EKHCO and
      EHHKCO were 9.50 and 6.87 microM, respectively. Dynamic light scattering showed
      that the surfactants complexed with plasmid DNA and siRNA to form stable
      nanoparticles at the concentrations below their critical micelle concentrations.
      The nanoparticles of the surfactants with pDNA and siRNA exhibited pH-sensitive
      hemolysis against rat red blood cells when the pH decreased from 7.4 to 5.5, the
      endosomal-lysosomal pH. The nanoparticles of EHHKCO showed more concentration
      dependent pH sensitivity than those of EKHCO. The EHHKCO and EKHCO nanoparticles
      of both pNDA and siRNA exhibited low cytotoxicity of at physiological pH. Both
      EKHCO and EHHKCO resulted in high intracellular uptake of pDNA and siRNA. EKHCO
      and EHHKCO resulted in relatively lower luciferase expression efficiency in U87
      cells than DOTAP but produced a much higher percentage of GFP expression in the
      transfected cells than DOTAP. Both EKHCO and EHHKCO mediated much higher gene
      silencing efficiency of luciferase and green fluorescence protein (GFP) than
      DOTAP. The surfactants were more effective for intracellular siRNA delivery than
      intracellular delivery of plasmid DNA. The pH-sensitive amphiphilic carriers are
      promising multifunctional carriers for intracellular delivery of nucleic acids.

PMID- 20672852
TI  - Protein adsorption onto polyelectrolyte layers: effects of protein hydrophobicity
      and charge anisotropy.
AB  - Ellipsometry was used to investigate the influence of ionic strength (I) and pH
      on the adsorption of bovine serum albumin (BSA) or beta-lactoglobulin (BLG) onto
      preabsorbed layers of two polycations: poly(diallyldimethylammonium chloride)
      (PDADMAC) or poly(4-vinylpyridine bromide) quaternized with linear aliphatic
      chains of two (QPVP-C2) or five (QPVP-C5) carbons. Comparisons among results for
      the three polycations reveal hydrophobic interactions, while comparisons between
      BSA and BLG-proteins of very similar isoelectric points (pI)-indicate the
      importance of protein charge anisotropy. At pH close to pI, the ionic strength
      dependence of the adsorbed amount of protein (Gamma) displayed maxima in the
      range 10 < I < 25 mM corresponding to Debye lengths close to the protein radii.
      Visualization of protein charge by Delphi suggested that these ionic strength
      conditions corresponded to suppression of long-range repulsion between
      polycations and protein positive domains, without diminution of short-range
      attraction between polycation segments and locally negative protein domains, in a
      manner similar to the behavior of PE-protein complexes in solution. (1-4) This
      description was consistent with the disappearance of the maxima at pH either
      above or below pI. In the former case, Gamma values decrease exponentially with
      I(1/2), due to screening of attractions, while in the latter case adsorption of
      both proteins decreased at low I due to strong repulsion. Close to or below pI
      both proteins adsorbed more strongly onto QPVP-C5 than onto QPVP-C2 or PDADMAC
      due to hydrophobic interactions with the longer alkyl group. Above pI, the
      adsorption was more pronounced with PDADMAC because these chains may assume more
      loosely bound layers due to lower linear charge density.

PMID- 20672853
TI  - Comparison of the specific incorporation of intracrystalline proteins into
      urinary calcium oxalate monohydrate and dihydrate crystals.
AB  - The aim of this study was to compare the comprehensive intracrystalline protein
      profiles of calcium oxalate monohydrate (COM) and dihydrate (COD) crystals
      precipitated from the same human urine samples. Three separate batches of COM and
      COD crystals were precipitated from pooled healthy human urine by the addition of
      sodium oxalate at calcium concentrations of 2 and 8 mM, respectively. Proteins in
      whole extracts of demineralised COM and COD crystals, as well as in spots excised
      from 2D-PAGE gels of the extracts, were identified using liquid chromatography
      and tandem mass spectrometry (LC-MS/MS). The number and type of individual
      proteins differed between COM and COD: 14 substantive proteins were found inside
      COM crystal extracts and 34 inside COD, with 9 proteins occurring in both crystal
      types. Numerous keratins were detected. However, in line with consensus in the
      proteomics literature, as well as a lack of published evidence linking them to
      urolithiasis, they were excluded as contaminants, leaving very few consistently
      detected proteins. On the basis of their known association with stone disease or
      identification in multiple runs, the principal proteins in COM crystal extracts
      were prothrombin fragment 1, protein S100A9, and IGkappaV1-5, while those in
      extracts of COD crystals included osteopontin, IGkappaV1-5, protein S100A9,
      annexin A1, HMW kininogen-1, and inter-alpha-inhibitor (IalphaI). In general,
      proteins incorporated into both hydromorphs were acidic (pI<6), smaller than 55
      kDa, and calcium binders. We concluded that the incorporation of proteins into
      urinary COM and COD crystals is selective and that only a few of the urinary
      proteins associated with the two hydromorphs are likely to play any significant
      role in stone pathogenesis.

PMID- 20672854
TI  - Structural basis for adenosylcobalamin activation in AdoCbl-dependent
      ribonucleotide reductases.
AB  - Class II ribonucleotide reductases (RNR) catalyze the formation of an essential
      thiyl radical by homolytic cleavage of the Co-C bond in their adenosylcobalamin
      (AdoCbl) cofactor. Several mechanisms for the dramatic acceleration of Co-C bond
      cleavage in AdoCbl-dependent enzymes have been advanced, but no consensus yet
      exists. We present the structure of the class II RNR from Thermotoga maritima in
      three complexes: (i) with allosteric effector dTTP, substrate GDP, and AdoCbl;
      (ii) with dTTP and AdoCbl; (iii) with dTTP, GDP, and adenosine. Comparison of
      these structures gives the deepest structural insights so far into the mechanism
      of radical generation and transfer for AdoCbl-dependent RNR. AdoCbl binds to the
      active site pocket, shielding the substrate, transient 5'-deoxyadenosyl radical
      and nascent thiyl radical from solution. The e-propionamide side chain of AdoCbl
      forms hydrogen bonds directly to the alpha-phosphate group of the substrate. This
      interaction appears to cause a "locking-in" of the cofactor, and it is the first
      observation of a direct cofactor-substrate interaction in an AdoCbl-dependent
      enzyme. The structures support an ordered sequential reaction mechanism with
      release or relaxation of AdoCbl on each catalytic cycle. A conformational change
      of the AdoCbl adenosyl ribose is required to allow hydrogen transfer to the
      catalytic thiol group. Previously proposed mechanisms for radical transfer in B12
      dependent enzymes cannot fully explain the transfer in class II RNR, suggesting
      that it may form a separate class that differs from the well-characterized
      eliminases and mutases.

PMID- 20672855
TI  - Evidence that histidine protonation of receptor-bound anthrax protective antigen
      is a trigger for pore formation.
AB  - The protective antigen (PA) component of the anthrax toxin forms pores within the
      low pH environment of host endosomes through mechanisms that are poorly
      understood. It has been proposed that pore formation is dependent on histidine
      protonation. In previous work, we biosynthetically incorporated 2-fluorohistidine
      (2-FHis), an isosteric analogue of histidine with a significantly reduced pK(a) (
      approximately 1), into PA and showed that the pH-dependent conversion from the
      soluble prepore to a pore was unchanged. However, we also observed that 2-FHisPA
      was nonfunctional in the ability to mediate cytotoxicity of CHO-K1 cells by LF(N)
      DTA and was defective in translocation through planar lipid bilayers. Here, we
      show that the defect in cytotoxicity is due to both a defect in translocation
      and, when bound to the host cellular receptor, an inability to undergo low pH
      induced pore formation. Combining X-ray crystallography with hydrogen-deuterium
      (H-D) exchange mass spectrometry, our studies lead to a model in which hydrogen
      bonds to the histidine ring are strengthened by receptor binding. The combination
      of both fluorination and receptor binding is sufficient to block low pH-induced
      pore formation.

PMID- 20672856
TI  - Volume exclusion and soft interaction effects on protein stability under crowded
      conditions.
AB  - Most proteins function in nature under crowded conditions, and crowding can
      change protein properties. Quantification of crowding effects, however, is
      difficult because solutions containing hundreds of grams of macromolecules per
      liter often interfere with the observation of the protein being studied. Models
      for macromolecular crowding tend to focus on the steric effects of crowders,
      neglecting potential chemical interactions between the crowder and the test
      protein. Here, we report the first systematic, quantitative, residue-level study
      of crowding effects on the equilibrium stability of a globular protein. We used a
      system comprising poly(vinylpyrrolidone)s (PVPs) of varying molecular weights as
      crowding agents and chymotrypsin inhibitor 2 (CI2) as a small globular test
      protein. Stability was quantified with NMR-detected amide (1)H exchange. We
      analyzed the data in terms of hard particle exclusion, confinement, and soft
      interactions. For all crowded conditions, nearly every observed residue
      experiences a stabilizing effect. The exceptions are residues for which
      stabilities are unchanged. At a PVP concentration of 100 g/L, the data are
      consistent with theories of hard particle exclusion. At higher concentrations,
      the data are more consistent with confinement. The data show that the crowder
      also stabilizes the test protein by weakly binding its native state. We conclude
      that the role of native-state binding and other soft interactions needs to be
      seriously considered when applying both theory and experiment to studies of
      macromolecular crowding.

PMID- 20672857
TI  - Introduction to main group chemistry.

PMID- 20672858
TI  - Pi-bonding and the lone pair effect in multiple bonds involving heavier main
      group elements: developments in the new millennium.

PMID- 20672859
TI  - Amine- and phosphine-borane adducts: new interest in old molecules.

PMID- 20672860
TI  - Ammonia-borane and related compounds as dihydrogen sources.

PMID- 20672862
TI  - Light-harvesting antenna system from the phototrophic bacterium Roseiflexus
      castenholzii.
AB  - Photosynthetic organisms have evolved diverse light-harvesting complexes to
      harness light of various qualities and intensities. Photosynthetic bacteria can
      have (bacterio)chlorophyll Q(y) antenna absorption bands ranging from
      approximately 650 to approximately 1100 nm. This broad range of wavelengths has
      allowed many organisms to thrive in unique light environments. Roseiflexus
      castenholzii is a niche-adapted, filamentous anoxygenic phototroph (FAP) that
      lacks chlorosomes, the dominant antenna found in most green bacteria, and here we
      describe the purification of a full complement of photosynthetic complexes: the
      light-harvesting (LH) antenna, reaction center (RC), and core complex (RC-LH). By
      high-performance liquid chromatography separation of bacteriochlorophyll and
      bacteriopheophytin pigments extracted from the core complex and the RC, the
      number of subunits that comprise the antenna was determined to be 15 +/- 1.
      Resonance Raman spectroscopy of the carbonyl stretching region displayed modes
      indicating that 3C-acetyl groups of BChl a are all involved in molecular
      interactions probably similar to those found in LH1 complexes from purple
      photosynthetic bacteria. Finally, two-dimensional projections of negatively
      stained core complexes and the LH antenna revealed a closed, slightly elliptical
      LH ring with an average diameter of 130 +/- 10 A surrounding a single RC that
      lacks an H-subunit but is associated with a tetraheme c-type cytochrome.

PMID- 20672863
TI  - Polymers for biomedical applications.

PMID- 20672861
TI  - Biophysical characterization of copolymer-protected gene vectors.
AB  - A copolymer-protected gene vector (COPROG) is a three-component gene delivery
      system consisting of a preformed DNA and branched polyethylenimine (bPEI) complex
      subsequently modified by the addition of a copolymer (P6YE5C) incorporating both
      poly(ethylene glycol) (PEG) and anionic peptides. Using fluorescence correlation
      spectroscopy (FCS) and atomic force microscopy (AFM), we characterized and
      compared the self-assembly of bPEI/DNA particles and COPROG complexes. In low
      salt buffer, both bPEI/DNA and COPROG formulations form stable nanoparticles with
      hydrodynamic radii between 60-120 nm. COPROG particles, as compared to bPEI/DNA,
      show greatly improved particle stability to both physiological salt as well as
      low pH conditions. Binding stoichiometry of the three-component COPROG system was
      investigated by dual-color fluorescence cross-correlation spectroscopy (FCCS). It
      was found that a significant fraction of P6YE5C copolymer aggregates with excess
      bPEI forming bPEI/P6YE5C "ghost complexes" with no DNA inside. The ratio of ghost
      particles to COPROG complexes is about 4:1. In addition, we find a large fraction
      of excess P6YE5C copolymer, which remains unbound in solution. We observe a 2-4
      fold enhanced reporter gene expression with COPROG formulations at various
      equivalents as compared to bPEI-DNA alone. We believe that both complex
      stabilization as well as the capture of excess bPEI into ghost particles induced
      by the copolymer is responsible for the improvement in gene expression.

PMID- 20672864
TI  - Biomaterials and drug delivery: past, present, and future.

PMID- 20672865
TI  - Topology of transmembrane channel-like gene 1 protein.
AB  - Mutations of transmembrane channel-like gene 1 (TMC1) cause hearing loss in
      humans and mice. TMC1 is the founding member of a family of genes encoding
      proteins of unknown function that are predicted to contain multiple transmembrane
      domains. The goal of our study was to define the topology of mouse TMC1 expressed
      heterologously in tissue culture cells. TMC1 was retained in the endoplasmic
      reticulum (ER) membrane of five tissue culture cell lines that we tested. We used
      anti-TMC1 and anti-HA antibodies to probe the topologic orientation of three
      native epitopes and seven HA epitope tags along full-length TMC1 after selective
      or complete permeabilization of transfected cells with digitonin or Triton X-100,
      respectively. TMC1 was present within the ER as an integral membrane protein
      containing six transmembrane domains and cytosolic N- and C-termini. There is a
      large cytoplasmic loop, between the fourth and fifth transmembrane domains, with
      two highly conserved hydrophobic regions that might associate with or penetrate,
      but do not span, the plasma membrane. Our study is the first to demonstrate that
      TMC1 is a transmembrane protein. The topologic organization revealed by this
      study shares some features with that of the shaker-TRP superfamily of ion
      channels.

PMID- 20672866
TI  - Ultrasonochemically conjugated metalloid/triblock copolymer nanocomposite and
      subsequent thin solid laminate growth for surface and interface studies.
AB  - Polymer and metalloid nanoparticles can be conjugated in a symphonized manner
      using ultrasonochemical force to obtain hybrid nanocomposites. The process is
      demonstrated using polymer poly(ethylene glycol) (PEG), metalloid SiO(2)@Ag, and
      triblock copolymer ABA. The acoustic microstreaming and cavitation force from the
      ultrasonics are crucial parameters that determine the harmonized PEG
      stabilization and ABA blending of the metalloid nanocomposites that are obtained.
      Surface plasmon resonance in the resulting hybrid systems are examined by UV-vis
      absorbance spectroscopy. The resulting PEG-stabilized SiO(2)-Ag conjugated with a
      triblock copolymer poly(p-dioxanone-co-caprolactone)-block-poly(ethylene oxide)
      block-poly(p-dioxanone-co-caprolactone) (PPDO-co-PCL-b-PEG-b-PPDO-co-PCL/ABA)
      (PEG-SiO(2)@Ag/ABA) shows a red shift of 20 nm (410 nm) from its initial
      resonance at 390 nm (PEG-SiO(2)@Ag). Nanocomposite particles were then spin
      coated on a glass substrate to obtain the growth of thin solid laminates
      (thickness 27 microm). Structural functionality was studied by FT-IR, (1)H NMR,
      and FT-Raman spectroscopy. Morphological properties were ensured from FE-SEM,
      HRTEM, AFM, and FIB-SEM. Identity and crystallinity of the prepared nanocomposite
      were confirmed by XRD analysis. A very low weight percentile loss of the
      fabricated nanocomposites ensures its high thermal stability. Fabricated
      nanocomposite laminate might have a role in coating, reinforcement, and
      resistance and as substrate additives for a variety of surface and interface
      studies. Further, the ultrasonochemical approach utilized here could also be a
      smart system to fabricate other heteronanostructures in a single platform.

PMID- 20672867
TI  - Inverse frequency weighting of fragments for similarity-based virtual screening.
AB  - This paper discusses the weighting of two-dimensional fingerprints for similarity
      based virtual screening, specifically the use of weights that assign greatest
      importance to the substructural fragments that occur least frequently in the
      database that is being screened. Virtual screening experiments using the MDL Drug
      Data Report and World of Molecular Bioactivity databases show that the use of
      such inverse frequency weighting schemes can result, in some circumstances, in
      marked increases in screening effectiveness when compared with the use of
      conventional, unweighted fingerprints. Analysis of the characteristics of the
      various schemes demonstrates that such weights are best used to weight the
      fingerprint of the reference structure in a similarity search, with the database
      structures' fingerprints unweighted. However, the increases in performance
      resulting from such weights are only observed with structurally homogeneous sets
      of active molecules; when the actives are diverse, the best results are obtained
      using conventional, unweighted fingerprints for both the reference structure and
      the database structures.

PMID- 20672868
TI  - Cytotoxicity of Cu(II) and Zn(II) 2,2'-bipyridyl complexes: dependence of IC50 on
      recovery time.
AB  - We measure the cytotoxicity of three metal complexes containing the 2,2'
      bypyridine ligand, Cu(bpy)(NCS)(2), 1, [Cu(bpy)(2)(H(2)O)](PF(6))(2), 2, and
      Zn(bpy)(2)(NCS)(2), 3, toward neuroblastoma cells (SK-N-SH) and ovarian cancer
      cells (OVCAR-3) using two different cell assays. The cells were exposed to
      various concentrations of the compounds for 1 h and the percent inhibition of
      cell growth, I, measured for various times after exposure, i.e., as a function of
      the recovery time t. After developing the theory showing the relationship between
      I and t, the cytotoxicity data were analyzed to reveal that the two copper
      complexes, 1 and 2, cause the cells to divide at a slower rate than the controls
      during the recovery period, but the zinc complex, 3, had little or no effect on
      cell division during the recovery period. The usual metric for reporting
      cytotoxicity is IC(50), which is the concentration of agent required to inhibit
      cell growth to 50% of the control population. However, since IC(50) can depend on
      the recovery time, t, as is the case for 1 and 2, reporting IC(50) for a single
      recovery time can hide important information about the long-time effects of a
      cytotoxic agent on the health of the cell population. Mechanistic studies with
      the compounds revealed that the copper complexes, 1 and 2, cleave closed circular
      pBR322 DNA in the presence of ascorbate, while the zinc complex, 3, does not
      facilitate DNA cleavage under the same conditions. This difference in DNA
      cleavage activity may be related to the fact that Cu(II) is redox active and can
      readily change its oxidation state, while Zn(II) is redox inert and cannot
      participate in a redox cycle with ascorbate to break DNA.

PMID- 20672869
TI  - Making the best of the early years: the Tambellup way.
AB  - INTRODUCTION: Tambellup is a small rural town in the Great Southern region of
      Western Australia (WA), approximately 300 km south-east of state capital Perth.
      Tambellup has a much higher Aboriginal population than the national average and
      achieved very positive results for year one children in 2007 regional Australian
      Early Development Index testing. In 2009 the Great Southern GP Network (which has
      a facilitating role in providing early intervention strategies to families with
      young children at risk of disadvantage) requested that public health staff at
      Edith Cowan University, Perth, WA undertake an exploratory study to discover the
      factors protective of children's development in Tambellup. This article describes
      the subsequent research and its findings. METHODS: This 2009 qualitative study
      interviewed both adult members of the local Aboriginal community (Noongar people;
      n = 23), and non-Aboriginal leaders from a cross-section of organisations,
      services and the community (n = 14) to determine what made growing up in
      Tambellup a positive experience. Aboriginal participants were introduced to the
      researchers by a local cultural consultant. Non-Aboriginal participants were
      initially sourced from a list provided by the GSGPN and extended by asking those
      listed to identify other appropriate contacts. Face-to-face interviews were
      carried out with Aboriginal participants and telephone interviews were undertaken
      with non-Aboriginal participants. All interviews were conducted using a standard
      schedule of questions as a guide, supplemented by clarifying and broadening
      questions from research team members. Data were analysed in a multi-stage process
      of collation, extraction of common themes and verification of themes with study
      participants and other stakeholders. Findings were presented to local Aboriginal
      leaders at a community meeting and a final report was prepared and circulated to
      community members. RESULTS: There was substantial evidence of widespread trust
      and positive relationships in this close-knit community, where adults looked out
      for and supported both their own and others' children. The primary school played
      a key role in supporting children's development even before children started
      school. Good relations generally existed between Aboriginal and non-Aboriginal
      residents, contributing to the stability of the population and providing many
      role models in successful cross-cultural relationships. CONCLUSION: Aboriginal
      people in Tambellup played significant but often under-recognised roles in
      promoting child and youth wellbeing in the community. The community had the
      capacity to respond to local needs and challenges. Communication channels were
      effective and there was a sense of belonging, pride and 'connectedness' in the
      community that promoted and supported a safe environment for children. High
      quality services and staff (eg school and community health centre) reinforced
      children's developmental opportunities. The results suggest that small rural
      communities offer significant and untapped resources for enhancing the health and
      wellbeing of children in the critical early years of life.

PMID- 20672870
TI  - Mental health collaborative care: a synopsis of the Rural and Isolated Toolkit.
AB  - CONTEXT: For those residing in rural and isolated parts of Canada, obtaining
      quality mental health services is often an unfulfilled wish. Rural and isolated
      communities share the problems of health status and access to care. Health
      deteriorates the greater the distance from urban areas in the following
      dimensions: lower life expectancy than the national average; higher rates of
      disability, violence, poisoning, suicide and accidental death; and more mental
      and physical health issues than those who live in urban areas. The Canadian
      Collaborative Mental Health Initiative (CCMHI) was formed to provide, in part, a
      practical means to encouraging collaborations between primary care and mental
      health providers. ISSUE: This article provides a synopsis of the Rural and
      Isolated (R&I) toolkit developed through the CCMHI, which was intended to develop
      primary care and mental health collaboration in such areas. This toolkit was
      developed using focus group discussions with mental health providers, and surveys
      completed by providers and consumers. LESSONS LEARNED: Key messages from the
      consultative process included: access to services; interprofessional education;
      consumer involvement; research and evaluation; models of collaboration; ethics;
      funding; and policy and legislation. A flow diagram was devised to detail the
      synthesis and practical application of the toolkit, as well as the challenges,
      key questions and principles of implementation associated with collaborative care
      initiatives in rural and isolated regions.

PMID- 20672871
TI  - Deciphering phenotypic diversity of Ralstonia solanacearum strains pathogenic to
      potato.
AB  - Based on the phylotype classification, we questioned how genetically and
      phenotypically diverse strains of Ralstonia solanacearum pathogenic to potato may
      be. We studied 129 European and Mediterranean strains along with 57 reference
      strains known to cover genetic diversity in this species. Phylogeny analysis was
      done on endoglucanase gene sequences. Pathogenicity to potato, tomato, and
      eggplant was established at 24 to 30 degrees C and 15 to 24 degrees C, whereas
      tests on banana were conducted at 24 to 30 degrees C. The ability to cause wilt
      on species of Solanaceae was shared by strains in all four phylotypes. Brown rot
      phylotypes IIB-1 and IIB-2 and phylotype IIB-27 established latent infections in
      banana, and Moko disease-causing phylotypes IIA-6, IIB-3, and IIB-4 were virulent
      to susceptible potato and tomato, addressing the question of host adaptation
      mechanisms, which may have undergone a similar bottleneck evolution. Cold
      tolerance ability is only shared on species of Solanaceae among brown rot
      phylotype IIB-1, which gathered the majority of European and Mediterranean
      strains. We surveyed strain LNPV24.25 as the first report of an emerging
      phylotype IIB-4NPB strain in France. These findings showed that pathogenicity
      traits of genetically identified strains still need to be understood, especially
      in the perspective of post-genomics comparative analysis, to understand bacterial
      speciation in the R. solanacearum species complex.

PMID- 20672872
TI  - 'Nice guys, your reps, right?'.

PMID- 20672874
TI  - Public awareness of motor neuron disease.

PMID- 20672875
TI  - Preliminary evaluation of a method for fitting hearing aids with extended
      bandwidth.
AB  - This paper describes a preliminary laboratory-based evaluation of a method for
      fitting hearing aids with an extended high-frequency response, called CAMEQ2-HF.
      Linear filtering was used to implement the CAMEQ2-HF-prescribed gains for speech
      with an input level of 65 dB SPL. The results obtained using four normal-hearing
      (NH) and fifteen hearing-impaired (HI) listeners showed: (1) The gains were
      sufficient to make components above 5 kHz audible when those components were
      presented alone, and when they were presented together with the lower-frequency
      components; (2) NH listeners preferred a wider bandwidth (10 or 7.5 kHz versus 5
      kHz) for both pleasantness and speech clarity, while HI listeners usually
      preferred a narrower bandwidth for pleasantness but a wider bandwidth for
      clarity; (3) HI listeners performed better on the 'S-test (detection of word
      final /s/ or /z/) with a wider than with a narrower bandwidth (7.5 versus 5 kHz);
      (4) Identification of vowel-consonant-vowel nonsense syllables improved with
      increasing bandwidth from 5 to 7.5 kHz for the NH but not for the HI listeners.

PMID- 20672876
TI  - Confocal imaging of Pseudomonas syringae pv. phaseolicola colony development in
      bean reveals reduced multiplication of strains containing the genomic island
      PPHGI-1.
AB  - Pseudomonas syringae pv. phaseolicola is the seed borne causative agent of halo
      blight in the common bean Phaseolus vulgaris. Pseudomonas syringae pv.
      phaseolicola race 4 strain 1302A contains the avirulence gene hopAR1 (located on
      a 106-kb genomic island, PPHGI-1, and earlier named avrPphB), which matches
      resistance gene R3 in P. vulgaris cultivar Tendergreen (TG) and causes a rapid
      hypersensitive reaction (HR). Here, we have fluorescently labeled selected
      Pseudomonas syringae pv. phaseolicola 1302A and 1448A strains (with and without
      PPHGI-1) to enable confocal imaging of in-planta colony formation within the
      apoplast of resistant (TG) and susceptible (Canadian Wonder [CW]) P. vulgaris
      leaves. Temporal quantification of fluorescent Pseudomonas syringae pv.
      phaseolicola colony development correlated with in-planta bacterial
      multiplication (measured as CFU/ml) and is, therefore, an effective means of
      monitoring Pseudomonas syringae pv. phaseolicola endophytic colonization and
      survival in P. vulgaris. We present advances in the application of confocal
      microscopy for in-planta visualization of Pseudomonas syringae pv. phaseolicola
      colony development in the leaf mesophyll to show how the HR defense response
      greatly affects colony morphology and bacterial survival. Unexpectedly, the
      presence of PPHGI-1 was found to cause a reduction of colony development in
      susceptible P. vulgaris CW leaf tissue. We discuss the evolutionary consequences
      that the acquisition and retention of PPHGI-1 brings to Pseudomonas syringae pv.
      phaseolicola in planta.

PMID- 20672877
TI  - Turnip mosaic virus (TuMV) is able to use alleles of both eIF4E and eIF(iso)4E
      from multiple loci of the diploid Brassica rapa.
AB  - Three copies of eIF4E and three copies of eIF(iso)4E have been identified and
      sequenced from a Turnip mosaic virus (TuMV)-susceptible, inbred, diploid Brassica
      rapa line, R-o-18. One of the copies of eIF4E lacked exons 2 and 3 and appeared
      to be a pseudogene. The two other copies of eIF4E and two of the three copies of
      eIF(iso)4E were isolated from a bacterial artificial chromosome library of R-o
      18. Using an Arabidopsis line (Col-0::dSpm) with a transposon knock-out of the
      eIF(iso)4E gene which resulted in a change from complete susceptibility to
      complete resistance to TuMV, complementation experiments were carried out with
      the two versions of eIF4E and the two versions of eIF(iso)4E. When transformed
      into Col-0::dSpm, all four Brassica transgenes complemented the Arabidopsis
      eIF(iso)4E knock-out, conferring susceptibility to both mechanical and aphid
      challenge with TuMV. One of the copies of eIF4E did not appear to support viral
      replication as successfully as the other copy of eIF4E or the two copies of
      eIF(iso)4E. The results show that TuMV can use both eIF4E and eIF(iso)4E from B.
      rapa for replication and, for the first time, that a virus can use eIF4E and
      eIF(iso)4E from multiple loci of a single host plant.

PMID- 20672878
TI  - Disruption of the Bcchs3a chitin synthase gene in Botrytis cinerea is responsible
      for altered adhesion and overstimulation of host plant immunity.
AB  - The fungal cell wall is a dynamic structure that protects the cell from different
      environmental stresses suggesting that wall synthesizing enzymes are of great
      importance for fungal virulence. Previously, we reported the isolation and
      characterization of a mutant in class III chitin synthase, Bcchs3a, in the
      phytopathogenic fungus Botrytis cinerea. We demonstrated that virulence of this
      mutant is severely impaired. Here, we describe the virulence phenotype of the
      cell-wall mutant Bcchs3a on the model plant Arabidopsis thaliana and analyze its
      virulence properties, using a variety of A. thaliana mutants. We found that
      mutant Bcchs3a is virulent on pad2 and pad3 mutant leaves defective in camalexin.
      Mutant Bcchs3a was not more susceptible towards camalexin than the wild-type
      strain but induced phytoalexin accumulation at the infection site on Col-0
      plants. Moreover, this increase in camalexin was correlated with overexpression
      of the PAD3 gene observed as early as 18 h postinoculation. The infection process
      of the mutant mycelium was always delayed by 48 h, even on pad3 plants, probably
      because of lack of mycelium adhesion. No loss in virulence was found when Bcchs3a
      conidia were used as the inoculum source. Collectively, these data led us to
      assign a critical role to the BcCHS3a chitin synthase isoform, both in fungal
      virulence and plant defense response.

PMID- 20672879
TI  - Production and perception of metrical patterns in Swedish children with language
      impairment.
AB  - The purpose of the present study was to investigate the relationship between
      perception and production of metrical patterns in Swedish children with language
      impairment (LI), in order to add to the knowledge on underlying explanations of
      LI. A further aim was to explore whether omissions are mainly related to prosodic
      aspects or to linguistic function. Children with LI omitted significantly more
      unstressed syllables than did children with typical language development.
      Exploration of the relationship between perception and production of phrasal
      stress patterns demonstrated that children with LI might be divided into three
      subgroups: Group a: children who perform better on perception than production;
      Group b: children who perform better on production than perception; and Group c:
      children with rather poor results on both perception and production.

PMID- 20672880
TI  - Clinical linguistics, cognitive neuropsychology and aphasia therapy.
AB  - Recent approaches to the study of language disorders in adults with focal brain
      damage (aphasia) have interpreted aphasic symptoms as impairments of particular
      aspects of the normal language system. Two distinct approaches along these lines,
      clinical linguistics and cognitive neuropsychology, have developed in parallel.
      Although there are differences between these approaches, there is also
      considerable methodological and substantive overlap. These similarities and
      differences are reviewed, with particular emphasis on the contributions of each
      approach to the development, implementation and interpretation of treatments for
      aphasic disorders of sentence production. It is argued that the field of clinical
      linguistics has defined and addressed numerous problems that cognitive
      neuropsychologists are beginning to confront as they attempt to use models of
      normal language processing to motivate treatment for aphasia.

PMID- 20672881
TI  - Discourse therapy in multilingual aphasia: a case study.
AB  - Analysis of the strategies used in narrative and conversational discourse enables
      a sensitive evaluation of the deficit in mild aphasic patients and a possible
      alternative to the therapist dealing with multilingual patients for whom standard
      aphasia testing is not useful. This study describes the characterization of the
      communication deficit in a multilingual aphasic patient and the development and
      subsequent implementation of a therapy programme. Standard testing and discourse
      analysis took place in four languages, but therapy took place in English.
      Improvement in conversational skills was noted in all four languages and the
      patient reported increased functional ability, particularly in a work context.
      The implications of this approach to assessment and therapy are discussed.

PMID- 20672882
TI  - Repair strategies in aphasic discourse; towards a collaborative model.
AB  - This paper proposes a collaborative model of repair in aphasic discourse, derived
      from the procedures of conversation analysis (CA). First, it is suggested that
      relative to other pragmatic orientations CA can offer a particularly illuminating
      and practically useful perspective on aphasic discourse. Repair strategies are
      then examined, first in relation to normal conversation then in relation to
      aphasic conversation' where one or more of the participants is aphasic. Next,
      Clark and Schaefer's CA-style model of conversational organization (1 987, 1989)
      is outlined, with attention to its relevance to the organization of repair in
      aphasic conversation. Finally, we apply this model in an analysis of some aphasic
      conversational sequences where the collaborative negotiation of repair is
      particularly evident.

PMID- 20672883
TI  - The mechanisms of phonemic paraphasia.
AB  - The mechanisms involved in the production of phonemic paraphasias are considered
      in this paper. Initially, a taxonomy of error types is provided where it is
      argued that there is a significant qualitative overlap in the kinds of errors
      witnessed in phonemic paraphasias and in segmental slips-of-the-tongue. There is
      ample historical precedent for the observation of this qualitative relation
      between fluent paraphasic errors and the phonemic errors in normal lapsus
      linguae. Some researchers have played down this qualitative similarity, but it is
      shown that when certain non-fluent aphasic phenomena are dissociated from the
      fluent paraphasias, the qualitative relation between paraphasias and slips
      remains entirely feasible. The metaphorical nature of the entire enterprise of
      characterizing phonemic paraphasias is briefly outlined, and finally the
      mechanisms at work are analysed from three rather different viewpoints: Merrill
      Garretts serial/hierarchical model of production; connectionist theory; and the
      phonological theory of underspecification.

PMID- 20672884
TI  - Abstruse neologism formation: parallel processing revisited.
AB  - Aspects of two different approaches to normal syllable formation (Berg, 1989;
      Clements, 1988, 1990) are incorporated into a model of abstruse neologism
      production characterized by redundant coding of sonority at various levels of
      parallel language processing. Data suggesting that the sonority profiles of
      abstruse neologisms accord with patterns found in legitimate English words are
      presented. Discussion explores neologism genesis from two well-known theoretical
      perspectives, illustrates how each theory of syllable formation might be
      instantiated within the model, and illustrates the role of sonority in
      constraining abstruse neologism production at several levels of parallel
      processing.

PMID- 20672885
TI  - Variability in speech dyspraxia.
AB  - In a volume dedicated to Professor Crystal, this study takes up some remarks of
      his (1982) regarding definitions of disorders and use of day-to-day clinical
      data. The topic chosen relates to the notion of variability in speech dyspraxia.
      Several different uses of the term are noted, but the one used in this paper
      focuses on variability of errors in a given word on a repeated-trials task. This
      task was employed to investigate whether, as previously claimed, speech
      dyspraxics differ from other pronunciation-disordered groups in terms of error
      variability. Results indicate that as a group they differ from spastic
      dysarthrics, but not from phonemic paraphasic speakers. On an individual basis,
      divisions are not as clearcut. Implications for assessment and speech production
      are considered in the light of this.

PMID- 20672886
TI  - The single-word lexicon of a severely mentally handicapped child.
AB  - Three criteria - phonetic form, semantic relevance and communicative saliency -
      are used to identify the single-word vocabulary of a young mentally handicapped
      child. The data are taken from video recordings made of the child playing at home
      and at school over a 12-month period. Inspection of the words reveals that the
      child exhibits phonological processes typical of younger, normally developing
      children and, when the complete vocabulary collected for this period is
      categorized following Nelson (1973), the proportion of word types used is
      comparable to those reported for normally developing children at the single-word
      stage. However. this childs use of single words is not restricted to the here-and
      now but is used to transcend time and space.

PMID- 20672887
TI  - Processes of phonological change in developmental speech disorders.
AB  - Two analytical frameworks for identifying and measuring the processes of
      phonological change in the speech of children with developmental speech disorders
      are described. The frameworks are illustrated by an examination and evaluation of
      longitudinal data from children with this type of disorder. The ways in which
      clinicians can use the two frameworks to guide treatment planning are discussed.

PMID- 20672888
TI  - Applying linguistic theory to speech-language pathology: the case for nonlinear
      phonology.
AB  - Application of knowledge from many related fields benefits the practice of speech
      language pathology. In the past 20 years, linguistic theory has provided a rich
      knowledge base for application. Phonological theories have provided frameworks
      for the description of the speech of unintelligible children in terms of coherent
      phonological systems, thus facilitating logical goal-setting for intervention. In
      this paper we suggest some of the possible implications of current nonlinear
      phonological frameworks for developmental phonology, and give an example of
      clinical application.

PMID- 20672889
TI  - Lexical verbs and language impairment: a case study.
AB  - Crystal has long advocated the extension of case-study approaches to language
      impairment. In the context of two other case studies in the literature, which
      highlight distinct problems in the linguistic systems of the individuals (both
      children) they consider, this study, of another child, identifies a particular
      difficulty with lexical verbs. It is suggested that while the data presented here
      suggest that it is worth investigating the issue of lexical verb deficits in
      language-impaired children, the major role for case studies is in identifying the
      range of possible deficits for multi-dimensional group studies of language
      impairment.

PMID- 20672890
TI  - Is a clinical sociolinguistics possible?
AB  - This paper considers the idea of developing a clinical sociolinguistics. Various
      areas of the field are examined, and the importance of the 'core' area of the
      correlation of non-linguistic variables with linguistic variables stressed.
      Issues concerning language and class, region, sex, age and context of utterance
      are investigated, together with the implications for clinical linguistics.
      Finally, the difficulty of integrating such issues into clinical assessment is
      explored, and a tentative step forward suggested along the lines of a 'clinical
      sociolinguistic checklist'.

PMID- 20672891
TI  - Project report: The linguistic characterization of aphasic speech.

PMID- 20672892
TI  - Vacuum-assisted en bloc resection of large convexity meningiomas. Technical note.
AB  - Convexity meningiomas are common tumors encountered by neurosurgeons. Retracting,
      grasping, and mobilizing large convexity meningiomas can be difficult and awkward
      as well as place unwanted forces on surrounding neurovascular structures. The
      authors present a safe alternative to traditional retraction and manipulation
      methods by using a modified bulb syringe connected to standard surgical suction
      to function as a vacuum retractor. This technique allows for rapid, safe, en bloc
      resection of large convexity meningiomas with little to no pressure on the
      surrounding brain. The authors present an illustrative case and describe and
      discuss the technique.

PMID- 20672893
TI  - Crossed aphasia elicited by intraoperative cortical and subcortical stimulation
      in awake patients.
AB  - OBJECT: Crossed aphasia (aphasia resulting from a right hemispheric lesion among
      right-handed patients) is rare. The authors describe for the first time transient
      crossed aphasia elicited by intraoperative electrostimulation of both cortex and
      white matter pathways in awake patients. METHODS: Three right-handed adults
      underwent surgery for a right-sided glioma. Because slight language disorders
      occurred during partial seizures or were identified on preoperative cognitive
      assessment, with right activations detected on language functional MR imaging in
      1 patient, awake craniotomy was performed using intraoperative cortico
      subcortical electrical functional mapping. RESULTS: Transient language
      disturbances were elicited by stimulating discrete cortical areas (inferior
      frontal gyrus and posterior part of the superior temporal gyrus) and white matter
      pathways (inferior frontooccipital fasciculus and arcuate fasciculus). A subtotal
      resection was achieved in all cases, according to functional boundaries.
      Postoperatively, 1 patient experienced a transient dysphasia, which resolved
      after speech rehabilitation, with no permanent deficit. CONCLUSIONS: These
      original findings highlight the possibility of finding crucial cortico
      subcortical language networks in the right hemisphere in a subgroup of atypical
      right-handed patients. These findings provide new insights into the neural basis
      of language, by underlining the role of the right inferior occipitofrontal
      fasciculus in semantics and that of the right arcuate fasciculus in phonology,
      and by supporting the hypothesis of a mirror organization between the right and
      left hemispheres. The authors suggest that, in right-handed patients, if language
      disturbances are detected during seizures or on presurgical neuropsychological
      assessment, especially when right activations are observed on language functional
      MR imaging, awake craniotomy with intraoperative language mapping should be
      considered.

PMID- 20672894
TI  - Improvement in recovery after experimental intracerebral hemorrhage using a
      selective cathepsin B and L inhibitor.
AB  - OBJECT: This study investigates a potential novel application of a selective
      cathepsin B and L inhibitor in experimental intracerebral hemorrhage (ICH) in
      rats. METHODS: Forty adult male Wistar rats received an ICH by stereotactic
      injection of 100 MUl of autologous blood or sham via needle insertion into the
      right striatum. The rats were treated with a selective cathepsin B and L
      inhibitor (CP-1) or 1% dimethyl sulfoxide sterile saline intravenously at 2 and 4
      hours after injury. Modified neurological severity scores were obtained and
      corner turn tests were performed at 1, 4, 7, and 14 days after ICH. The rats were
      sacrificed at 3 and 14 days after ICH for immunohistological analysis of tissue
      loss, neurogenesis, angiogenesis, and apoptosis. RESULTS: The animals treated
      with CP-1 demonstrated significantly reduced apoptosis as well as tissue loss
      compared with controls (p < 0.05 for each). Neurological function as assessed by
      modified neurological severity score and corner turn tests showed improvement
      after CP-1 treatment at 7 and 14 days (p < 0.05). Angiogenesis and neurogenesis
      parameters demonstrated improvement after CP-1 treatment compared with controls
      (p < 0.05) at 14 days. CONCLUSIONS: This study is the first report of treatment
      of ICH with a selective cathepsin B and L inhibitor. Cathepsin B and L inhibition
      has been shown to be beneficial after cerebral ischemia, likely because of its
      upstream regulation of the other prominent cysteine proteases, calpains, and
      caspases. While ICH may not induce a major component of ischemia, the cellular
      stress in the border zone may activate these proteolytic pathways. The
      observation that cathepsin B and L blockade is efficacious in this model is
      provocative for further investigation.

PMID- 20672895
TI  - Diagnostic value of magnetic resonance imaging in perimesencephalic and
      nonperimesencephalic subarachnoid hemorrhage of unknown origin.
AB  - OBJECT: The aim of this study was to evaluate the diagnostic value of MR imaging
      in perimesencephalic (PM) and nonperimesencephalic (non-PM) subarachnoid
      hemorrhage (SAH) of unknown origin. METHODS: The authors conducted a
      retrospective review of all patients with SAH (1226 patients) in their department
      between January 1991 and December 2008. Included in the study were cases of
      spontaneous SAH diagnosed using CT scans obtained within 24 hours of the initial
      symptoms and initially negative digital subtraction (DS) angiograms. Patients
      with traumatic SAH and an unknown history were excluded from the study. Patients
      with initially negative DS angiograms were divided into 2 groups: Group 1, a
      typically PM bleeding pattern (PM SAH); and Group 2, a non-PM bleeding pattern
      (non-PM SAH) such as hemorrhage in the sylvian or interhemispheric fissure.
      Cranial MR imaging including the craniocervical region was performed within 72
      hours after SAH was diagnosed in all patients in Groups 1 and 2. RESULTS: One
      thousand sixty-eight patients underwent DS angiography, and among them were 179
      (16.7%) with negative angiograms--47 patients (26.3%) from Group 1 and 132
      patients (73.7%) from Group 2. Magnetic resonance imaging demonstrated no
      bleeding sources in any case (100% negative). Thirty-four patients in Group 1 and
      120 patients in Group 2 underwent a second DS angiography study. Digital
      subtraction angiography revealed an aneurysm as the bleeding source in 1 case in
      Group 1 and in 13 cases in Group 2. CONCLUSIONS: Magnetic resonance imaging of
      the brain and craniocervical region did not produce additional benefit for the
      detection of a bleeding source and the therapy administered for PM SAH and non-PM
      SAH (100% negative). The costs of this examination exceeded the clinical value.
      Despite the results of this study, MR imaging should be discussed on a case-by
      case basis because rare bleeding sources are periodically diagnosed in cases of
      non-PM SAH. A second-look DS angiogram is necessary because aneurysmal hemorrhage
      occasionally produces PM SAH as well as non-PM SAH. Further prospective studies
      are needed to verify the authors' results in the future.

PMID- 20672896
TI  - Effects of sodium selenite and amiloride on calvarial calcification in closing
      small cranial defects.
AB  - OBJECT: Fresh autogenous bone graft is the most preferred osteoplastic material,
      whether the purpose is cosmetic, psychological, or for the protection of the
      brain. These grafts are not rejected and do not react immunologically. The aim of
      this study was to evaluate the efficacy of autogenous fat rolled with bone dust
      derived from the bur hole in closing small cranial defects. Additionally, the
      authors examined the morphological and biochemical effects of Na selenite and
      amiloride on calvarial calcification. METHODS: The study group consisted of 20
      domestic pigs. These animals were randomly divided into 4 groups. A bur hole with
      a diameter of 10 mm was made at the right parietal region in all animals, and
      then the periosteum around the bur hole was cauterized following exposure of the
      dura mater. The dura was coagulated with bipolar cautery. Group 1 (controls):
      only a bur hole was opened, and it was then closed with a mixture of the bone
      dust that had been created during the opening of the bur hole and fat tissue that
      was taken from the animal's neck. Group 2 (amiloride): 1 nmol/g body weight of
      amiloride was applied subcutaneously within 15 minutes after closure of the bur
      hole with bone dust and fat, and then amiloride was applied once a day for 4
      weeks. Group 3 (Na selenite): 30 nmol/g body weight of Na selenite was applied
      subcutaneously within 30 minutes after closure of the bur hole with bone dust and
      fat, and then Na selenite was applied once a day for 4 weeks. Group 4 (amiloride
      and Na selenite): 1 nmol/g body weight of amiloride was applied subcutaneously at
      15 minutes, and 30 nmol/g body weight of Na selenite was applied subcutaneously
      at 30 minutes after closure of the bur hole with bone dust and fat, and these 2
      injections were repeated once a day for 4 weeks. At the end of 4 weeks, the
      animals were anesthetized to evaluate the closure of the bur hole. Tissue samples
      were obtained for ultrastructural and biochemical examination. RESULTS: The
      defect was covered with diffuse connective tissue in the control group. Although
      multiple capillary vessels were present, the authors did not observe osteogenic
      differentiation. Histological examination of the second group revealed osteogenic
      changes. Although new matrix was formed, calcification was not detected. The
      authors observed fibroblast, collagen fibers, and dense connective tissue filled
      with capillary in the third group of pigs, which had undergone Na selenite
      application. Calcification was not detected in this group. Both connective and
      osteogenic tissue were observed in specimens obtained in the fourth group, which
      had undergone amiloride and Na selenite application. CONCLUSIONS: The authors
      experimentally evaluated the supplementary osteogenic effects of Na selenite and
      amiloride by using them separately and together. The findings seem promising as a
      lead-in to new studies in restoring cranial defects.

PMID- 20672897
TI  - Transfer of the phrenic nerve to the posterior division of the lower trunk to
      recover thumb and finger extension in brachial plexus palsy.
AB  - OBJECT: Hand function is severely impaired in cases of lower root avulsion. In
      the present study, the authors investigated the clinical effectiveness and safety
      of phrenic nerve transfer to the posterior division of the lower trunk of the
      brachial plexus to recover thumb and finger extension. METHODS: Between 2004 and
      2006, 10 patients with brachial plexus palsy underwent phrenic nerve transfer as
      part of a strategy for surgical reconstruction of their plexuses. The mean
      patient age of was 27.2 years (range 18-44 years), and the mean interval from
      injury to surgery was 5.7 months (range 3-9 months). The phrenic nerve was always
      transferred to the posterior division of the lower trunk. RESULTS: The follow-up
      of the patients ranged from 2.5 to 4.4 years, with an average follow-up length of
      3.5 years. There were no major complications related to the surgery. Eight
      patients recovered to Grade 3 or better (Medical Research Council grade) in
      extensor digitorum strength, and 7 patients recovered to Grade 3 or better in
      extensor pollicis strength. None of the patients had any clinical signs or
      symptoms of respiratory insufficiency. CONCLUSIONS: Satisfactory thumb and finger
      extension can be achieved by phrenic nerve transfer to the posterior division of
      the lower trunk of the brachial plexus. This procedure is simple and less
      traumatic than that of transferring the phrenic nerve to the radial nerve. It is
      indicated in cases in which the brachial plexus is relatively intact at the
      division level.

PMID- 20672898
TI  - Cerebral aneurysm clips in the 3-tesla magnetic field. Laboratory investigation.
AB  - OBJECT: The aim of this study was to evaluate cerebral aneurysm clips, and to
      know in more detail the characteristics of currently available clips in the 3-T
      magnetic field. METHODS: According to the protocol recommended by the American
      Society for Testing and Materials (ASTM), the authors conducted quantitative
      evaluation for displacement force and qualitative evaluation for torque in 52
      aneurysm clips and 48 samples of raw materials in the 3-T environment. RESULTS:
      The largest displacement force occurred near the bore opening, and the force was
      directed to the isocenter. Deflection angles of all objects in this study were
      within 45 degrees . The translational force in the peripheral position in the
      bore was larger than that in the center, and the translational force in the
      magnetic field was proportional to the weight of the objects. The proportion
      coefficients varied depending on the metallic materials. In the titanium alloy,
      the deflection angle was also detected to be approximately 2 degrees , although
      no response was observed in titanium in a previous report. This behavior was
      similar to that of the Elgiloy and Phynox materials in the 1.5-T environment. No
      difference was observed among the groups of shapes (straight, bent, and
      fenestrated). The amount of torque that occurred was dependent on the clip's or
      material's loop and bent shape. The torque on the titanium was perpendicular to
      the torque on the other materials (which was perpendicular to the magnetic
      field). CONCLUSIONS: Care must be taken with patients near the bore opening while
      moving them to the center of the magnet's bore on the MR imaging table. Although
      all the clips examined in this study met the ASTM requirements, the titanium
      alloy clips are preferable in the 3-T environment for safety's sake. Suitably
      sized clips should be selected for the aneurysm size, because the translational
      force increases proportionally to the object's weight.

PMID- 20672899
TI  - Hemangiopericytoma: long-term outcome revisited. Clinical article.
AB  - OBJECT: Hemangiopericytomas are rare tumors that behave aggressively with a high
      rate of local recurrence and distant metastases. With the aim of determining the
      outcome and response to various treatment modalities, a series of 39 patients who
      underwent microsurgical resection for primary meningeal hemangiopericytoma over a
      24-year period is presented. METHODS: Patients with hemangiopericytoma were
      identified from histopathology records and their medical records were analyzed
      retrospectively by 2 independent reviewers to collect data on surgical treatment,
      adjuvant therapy, postoperative course, local or distant recurrence, and follow
      up. RESULTS: Of the 39 patients, 19 were male and 20 were female. Mean patient
      age was 44.1 years. Thirty-four tumors were intracranial and 5 were spinal. The
      mean follow-up period was 123 months. Twenty-eight patients developed local
      recurrence. The recurrence rate at 1, 5, and 15 years was 3.5%, 46%, and 92%,
      respectively. Extraneural metastasis occurred in 8 patients (26%) at an average
      of 123 months after initial surgery. Recurrences and metastases were treated by
      surgical excision, external beam radiation therapy (EBRT), chemotherapy, and/or
      stereotactic radiosurgery. Adjuvant EBRT following initial surgery was found to
      extend the disease-free interval from 154 months to 254 months, although it did
      not prevent the development of metastasis. In those patients with EBRT and
      complete resection, the mean recurrence-free interval was found to be 126.3
      months longer (p = 0.04) and overall survival 126 months longer than without
      EBRT. Furthermore, adjusting for resection, patients undergoing EBRT had 0.33
      times increased risk of recurrence compared with those who did not (p = 0.03). A
      majority of patients remained able to live independently despite revision surgery
      for recurrence. CONCLUSIONS: The mean follow-up of this patient series represents
      the longest follow-up duration published to date and demonstrates extended
      survival in a significant number of patients with hemangiopericytoma. Gross-total
      resection followed by adjuvant EBRT provides patients with the highest
      probability of an increased recurrence-free interval and overall survival.
      Prolonged survival justifies long-term follow-up and aggressive treatment of
      initial, recurrent, and metastatic disease.

PMID- 20672900
TI  - Sixteen-year single-surgeon experience with coil embolization for ruptured
      intracranial aneurysms: recurrence rates and incidence of late rebleeding.
      Clinical article.
AB  - OBJECT: Over a 16-year period, 570 patients presenting with acute aneurysmal
      subarachnoid hemorrhage were successfully treated using endosaccular coil
      embolization within 30 days of hemorrhage by a single surgeon. Patients were
      followed to assess the stability of aneurysm occlusion and its longer-term
      efficacy in protecting against rebleeding. METHODS: Patients were followed for 6
      to 191 months (mean 73.7 months, median 67 months) by clinical review,
      angiography performed at 6 and 24 months posttreatment, and questionnaires sent
      via the postal service every 5 years. Late rebleeding was defined as > 30 days
      after treatment. RESULTS: Stable angiographic occlusion was evident in 74.5% of
      small, 72.2% of large, and 60% of giant aneurysms. Recurrent filling was found in
      119 (26.3%) of 452 aneurysms. Rebleeding was diagnosed in 9 patients (6 treated
      aneurysms) and occurred between 2 and 114 months posttreatment. It was due to
      aneurysm recurrence in 6 patients, rupture of a coincidental untreated aneurysm
      in 2 patients, and rupture of a de novo aneurysm in 1 patient. Rebleeding
      occurred in 3 (2.5%) of 119 unstable aneurysms and in 3 (0.9%) of 333 stable
      aneurysms, as seen on initial follow-up angiography studies. Annual rebleeding
      rates ranged from 0.2% to 0.6% for all causes and from 0.2% to 0.4% for
      rebleeding of treated aneurysms. No rebleeding was recorded after the first
      decade, with 138 patients having more than 10 years of follow-up. CONCLUSIONS:
      Periodic follow-up with angiographic studies after coil embolization is
      recommended to identify aneurysm recurrence and patients at a high risk of late
      rebleeding in the medium term. More frequent follow-up is recommended for
      patients harboring coincidental unruptured aneurysms.

PMID- 20672901
TI  - Use of lumboperitoneal shunts with the Strata NSC valve: a single-center
      experience.
AB  - OBJECT: The lumboperitoneal (LP) shunt with the adjustable PS Medical Strata NSC
      LP valve and small lumen peritoneal catheter was introduced in the authors' unit
      in 2007. The object of this study was to audit the unit's experience with this
      new shunt system. METHODS: The authors performed a retrospective review of the
      clinical records of patients who underwent Strata NSC LP shunt insertion.
      Demographic and clinical data as well as information about complications and
      revisions were reported. RESULTS: Between August 2007 and November 2009, 20
      patients underwent placement of an LP shunt with an adjustable Strata NSC valve
      and small lumen peritoneal catheter at the authors' institution. Their mean age
      was 40.3 years and the mean duration of follow-up was 12 months. Preoperatively,
      18 patients had headache and 15 patients had visual signs and symptoms. Fourteen
      of the 18 patients with preoperative headache did not complain of headache
      postoperatively, and 4 had headache that was found not to be related to shunt
      function. Two of the patients with preoperative visual complaints had ongoing
      visual problems postoperatively. None of the patients had infection or subdural
      hematoma. The only overdrainage symptoms occurred in association with spontaneous
      readjustment of the valve and resolved when the valve was reset. Thirteen
      patients (65%) did not require shunt revision. Seven patients (35%) required 13
      shunt exploration or revision procedures, mainly due to distal obstruction.
      Placement of an LP shunt failed to completely resolve the raised intracranial
      pressure problem in 2 patients. CONCLUSIONS: The use of the Strata NSC valve and
      small lumen peritoneal catheter is effective in treating pseudotumor cerebri and
      is beneficial in terms of markedly reducing overdrainage complications compared
      with other reported series of cases in which an LP shunt has been placed.
      However, the use of the Strata NSC valve and small lumen peritoneal catheter did
      not have a marked impact on other causes of shunt failure, particularly distal
      obstruction.

PMID- 20672902
TI  - Coils and rebleeding.

PMID- 20672903
TI  - Effect of ultrasound-guided aspiration of hydrosalpingeal fluid during oocyte
      retrieval on the outcomes of in vitro fertilisation-embryo transfer: a randomised
      controlled trial (NCT01040351).
AB  - OBJECTIVE: To determine whether the ultrasound-guided aspiration of
      hydrosalpingeal fluid at the time of oocyte retrieval can improve the outcomes of
      in vitro fertilisation-embryo transfer (IVF-ET). PATIENTS: One hundred and ten
      women with ultrasound-visible hydrosalpinges were randomised to two groups based
      on computer generated randomisation list. Fifty-four women underwent ultrasound
      guided aspiration of hydrosalpingeal fluid prior to IVF-ET and 53 women underwent
      IVF-ET without any prior intervention. RESULTS: Patients who underwent aspiration
      of hydrosalpinges demonstrated a significantly increased implantation, clinical
      pregnancy rates. Among the patients in the aspiration group, the implantation
      rate and pregnancy rates were higher in the subgroup of patients with no
      reaccumulation of hydrosalpingeal fluid within the first 2 weeks after aspiration
      compared to patients with reaccumulation of hydrosalpingeal fluid within the
      first 2 weeks after aspiration, but this difference failed to reach statistical
      significance. Furthermore, no pregnancies occurred in the four patients with
      uterine fluid collection detected during IVF-ET cycles. CONCLUSION: The
      aspiration of hydrosalpingeal fluid at the time of oocyte retrieval is simple,
      safe and effective procedure for treatment of patients with ultrasound-visible
      hydrosalpinges particularly those without rapid reaccumulation of hydrosalpingeal
      fluid after aspiration or uterine fluid collection during the IVF-ET cycles.

PMID- 20672904
TI  - Germline study of AR gene of Indian women with ovarian failure.
AB  - OBJECTIVE: Present study was designed for carrying out the mutational analysis of
      the entire Androgen receptor (AR) gene including two microsatellite (CAG)n,
      (GGN)n, promoter region in cases of premature ovarian failure (POF) and primary
      amenorrhea (PA). DESIGN: Previous reports of AR knockout mice model showed POF
      phenotype, this draws an attention on the role of AR gene in the aetiology of POF
      for the case-control association studies in POF samples (n = 133), PA samples (n
      = 63) and control samples (n = 200). RESULTS: We identified six mutations
      including four novel mutations, i.e. c.636G > A, c.1885 + 9C > A, c.1948A > G,
      c.1972C > A, and two previously reported mutations, i.e. c.639G > A, c.2319-78T >
      G. Repeat length variation was noted in the two microsatellite regions CAG and
      GGN, located in the coding region of exon 1 at the N-terminal region of the AR
      gene. The CAG repeat length was homogeneously distributed with the same frequency
      and no association among all cases and controls. The GGN repeat showed a
      significant association among the SS and SL allele with p = 0.0231 and p =
      0.0476, respectively, among the POF/control samples. CONCLUSIONS: Thus, AR gene
      mutations may play a role in the genetic cause of POF. Identification of the
      underlying genetic alteration of the AR gene is important for a proper diagnosis
      of POF subjects.

PMID- 20672905
TI  - Pheochromocytoma and medullary thyroid carcinoma in a pregnant multiple endocrine
      neoplasia-2A patient.
AB  - OBJECTIVE: We describe a rare combination of pheochromocytoma and medullary
      thyroid carcinoma (MTC) during pregnancy. METHODS: Twenty-three-years old lady,
      primigravida, was detected to be hypertensive at 12 weeks of gestation and was
      found to have left adrenal mass on routine obstetric scan. She had a goitre on
      examination which was proven to be MTC on fine needle aspiration cytology. Twenty
      four hours urinary vanillyl mandelic acid and serum calcitonin levels were
      elevated. After adequate alpha and beta blockade she underwent left adrenalectomy
      during second trimester of gestation with no significant perioperative
      complications. Twelve days later she underwent total thyroidectomy. RESULTS:
      Adrenal mass was confirmed to be pheochromocytoma while MTC was confirmed in the
      thyroidectomy specimen. Post-operatively, she was normotensive and delivered a
      healthy female baby at term. Both mother and the baby tested positive for
      germline RET mutation (C634W) in exon 11. CONCLUSION: We describe a rare case of
      pregnant multiple endocrine neoplasia-2A patient with pheochromocytoma and MTC.

PMID- 20672906
TI  - Inhibitory effect of curcumin on uterine leiomyoma cell proliferation.
AB  - OBJECTIVE: Uterine leiomyomas are the most common gynaecological benign tumour
      and greatly affect reproductive health and wellbeing. They are the predominant
      indication for hysterectomy in premenopausal women. Curcumin, a well-known
      component of turmeric, has been reported to prevent various diseases such as
      cancer, diabetes and obesity. Previous study reported that curcumin represses the
      proliferation of several tumour cells. However, there has not been a precise
      characterisation of the curcumin-induced inhibition of uterine leiomyoma cells.
      In this study, we investigated the inhibitory effect of curcumin on leiomyoma
      cells proliferation. STUDY DESIGN: Eker rat-derived uterine leiomyoma cell lines
      (ELT-3 cells) were used. Cell proliferation was assessed by counting the number
      of cells and MTS assay. The activation of peroxisome proliferator-activated
      receptor-gamma (PPARgamma) was evaluated by luciferase assay. RESULTS: We found
      that curcumin significantly inhibited ELT-3 cell proliferation. PPARgamma was
      expressed in ELT-3 cells and curcumin acted as a PPARgamma ligand. This
      inhibitory effect of curcumin was attenuated by the treatment of cells with
      PPARgamma antagonist. CONCLUSION: These experimental findings in vitro show that
      the inhibitory effect of curcumin on ELT-3 cell proliferation occurs through the
      activation of PPARgamma. Curcumin may be useful as an alternative therapy for
      uterine leiomyoma.

PMID- 20672907
TI  - Why kisspeptin is such important for reproduction?
AB  - Recently discovered neuropeptide called kisspeptin is thought to be an essential
      gatekeeper in control of reproduction. Kisspeptin, the product of KiSS-1 gene and
      its G protein-coupled receptor GPR54 play a master role in the puberty period and
      fertility. This 54 amino acid peptide known also as metastatin, because of its
      metastasis suppression ability is also implicated in tumour biology.
      Kisspeptin/GPR54 system activates the hypothalamus-pituitary-ovarian axis. Its
      mechanism is not clearly understood. Kisspeptin influence is found above more at
      the level of hypothalamus but also at the pituitary and ovaries level. Kisspeptin
      can directly stimulate GnRH secretion from arcuate nucleus of hypothalamus. It is
      thought that kisspeptin plays an essential role in the metabolic regulation of
      fertility. In negative energy balance conditions an expression of KiSS-1 gene is
      decreased. Inactivating GPR54 mutations cause hypogonadotropic hypogonadism in
      humans. Simultaneously, mutations which increase GPR54 signalling are connected
      with gonadotropin-dependent premature puberty. Lately, possible therapeutic role
      of kisspeptin administration has been discussed. It was stated that kisspeptin
      might be used to manipulate the hypothalamic-pituitary-gonadal axis in humans.
      However, further studies are essential to reveal the exact mechanism and role of
      GPR54 agonists and antagonists applications. Moreover, the role of kisspeptin in
      the aspect of detection and treatment of specific cancers should be discovered.

PMID- 20672908
TI  - Maternal ethnicity influences on neonatal respiratory outcomes after antenatal
      corticosteroid use for anticipated preterm delivery.
AB  - OBJECTIVE: To explore the influence of maternal ethnicity on neonatal outcomes
      after antenatal corticosteroid administration. METHODS: A retrospective review of
      ethnicity, maternal factors, and neonatal birth outcomes was performed for
      preterm births at a single institution. Cases were limited to women who received
      antenatal corticosteroids. The impact of ethnicity on specific neonatal
      respiratory outcomes and mortality was analyzed by bivariate comparisons and by
      logistic regression analysis. RESULTS: Complete ethnicity data were obtained for
      548 women. Controlling for gestational age at delivery, diabetes, whether the
      subject completed a course of steroids, and the dosing of the steroids, logistic
      regression demonstrated that ethnicity was independently associated with
      respiratory distress syndrome (compared to Caucasians: African-Americans OR 0.49
      (95% CI 0.29-0.85); Filipinos OR 0.45 (95% CI 0.21-0.96). CONCLUSIONS: Ethnicity
      is independently associated with neonatal respiratory outcomes after antenatal
      corticosteroid use. Perhaps individualized dosing of antenatal corticosteroids is
      needed to further improve neonatal outcomes.

PMID- 20672909
TI  - Alcoholic fatty liver disease and alcoholic liver cirrhosis may be differentiated
      with mean platelet volume and platelet distribution width.

PMID- 20672910
TI  - The dangerous liaison between iNKT cells and dendritic cells: does it prevent or
      promote autoimmune diseases?
AB  - Invariant natural killer T (iNKT) cells represent an important regulatory T-cell
      subset that perceives signals of danger and/or cellular distress and modulate the
      adaptive immune response accordingly. In the presence of pathogens, iNKT cells
      acquire an adjuvant function that is fundamental to boost anti-microbial and anti
      tumor immunity. At the same time, iNKT cells can play a negative regulatory
      function to maintain peripheral T-cell tolerance toward self-antigens and to
      prevent autoimmune disease. Both these effects of iNKT cells involve the
      modulation of the activity of dendritic cells (DCs) through cell-cell
      interaction. Indeed, iNKT cells can either boost Th1 immunity by enhancing
      maturation of pro-inflammatory DCs or promote immune tolerance through the
      maturation of tolerogenic DCs. This dual action of iNKT cells opens questions on
      the modalities by which a single-cell subset can exert opposite effects on DCs
      and may even put in question the overall immunosuppressive properties of iNKT
      cells. This review presents the large body of evidence that shows the ability of
      iNKT cells to negatively regulate autoimmunity and to prevent autoimmune diseases
      including multiple sclerosis, type 1 diabetes, rheumatoid arthritis, and systemic
      lupus erythematosus. In addition, an update is provided on the mechanisms of iNKT
      DCs interactions and how this can result in inflammatory or tolerogenic
      responses.

PMID- 20672911
TI  - Deep brain stimulation between 1947 and 1987: the untold story.
AB  - Deep brain stimulation (DBS) is the most rapidly expanding field in neurosurgery.
      Movement disorders are well-established indications for DBS, and a number of
      other neurological and psychiatric indications are currently being investigated.
      Numerous contemporary opinions, reviews, and viewpoints on DBS fail to provide a
      comprehensive account of how this method came into being. Misconceptions in the
      narrative history of DBS conveyed by the wealth of literature published over the
      last 2 decades can be summarized as follows: Deep brain stimulation was invented
      in 1987. The utility of high-frequency stimulation was also discovered in 1987.
      Lesional surgery preceded DBS. Deep brain stimulation was first used in the
      treatment of movement disorders and was subsequently used in the treatment of
      psychiatric and behavioral disorders. Reports of nonmotor effects of subthalamic
      nucleus DBS prompted its use in psychiatric illness. Early surgical interventions
      for psychiatric illness failed to adopt a multidisciplinary approach;
      neurosurgeons often worked "in isolation" from other medical specialists. The
      involvement of neuro-ethicists and multidisciplinary teams are novel standards
      introduced in the modern practice of DBS for mental illness that are essential in
      avoiding the unethical behavior of bygone eras. In this paper, the authors
      examined each of these messages in the light of literature published since 1947
      and formed the following conclusions. Chronic stimulation of subcortical
      structures was first used in the early 1950s, very soon after the introduction of
      human stereotaxy. Studies and debate on the stimulation frequency most likely to
      achieve desirable results and avoid side effects date back to the early days of
      DBS; several authors advocated the use of "high" frequency, although the exact
      frequency was not always specified. Ablative surgery and electrical stimulation
      developed in parallel, practically since the introduction of human stereotactic
      surgery. The first applications of both ablative surgery and chronic subcortical
      stimulation were in psychiatry, not in movement disorders. The renaissance of DBS
      in surgical treatment of psychiatric illness in 1999 had little to do with
      nonmotor effects of subthalamic nucleus DBS but involved high-frequency
      stimulation of the very same brain targets previously used in ablative surgery.
      Pioneers in functional neurosurgery mostly worked in multidisciplinary groups,
      including when treating psychiatric illness; those "acting in isolation" were not
      neurosurgeons. Ethical concerns have indeed been addressed in the past, by
      neurosurgeons and others. Some of the questionable behavior in surgery for
      psychiatric illness, including the bygone era of DBS, was at the hands of
      nonneurosurgeons. These practices have been deemed as "dubious and precarious by
      yesterday's standards."

PMID- 20672912
TI  - Deep brain stimulation for obsessive-compulsive disorder: past, present, and
      future.
AB  - Obsessive-compulsive disorder (OCD) is a psychiatric illness that can lead to
      chronic functional impairment. Some patients with severe, chronic OCD have been
      treated with ablative neurosurgical techniques over the past 4 decades. More
      recently, deep brain stimulation (DBS) has been investigated as a therapy for
      refractory OCD, and the procedure was granted a limited humanitarian device
      exemption by the FDA in 2009. In this article, the authors review the development
      of DBS for OCD, describe the current understanding of the pathophysiological
      mechanisms of the disorder and how the underlying neural circuits might be
      modulated by DBS, and discuss the clinical studies that provide evidence for the
      use of this evolving therapy. The authors conclude with suggestions for how a
      combined basic science and translational research approach could drive the
      understanding of the neural mechanisms underlying OCD as well as the clinical
      effectiveness of DBS in the setting of recalcitrant disease.

PMID- 20672913
TI  - Deep brain stimulation of the orbitofrontal projections for the treatment of
      intermittent explosive disorder.
AB  - Intermittent explosive disorder (IED) is characterized by a dysfunction in the
      greater limbic system leading an individual to experience sudden aggressive
      behavior with little or no environmental perturbation. This report describes a
      procedure for the treatment of IED in a 19-year-old woman with a history of IED,
      having had episodes of severe violent attacks against family, dating to early
      childhood. Due to the severity and intractability of the illness, deep brain
      stimulation was performed, targeting the orbitofrontal projections to the
      hypothalamus. The patient's history and the procedure, management, and rationale
      are described in detail.

PMID- 20672914
TI  - Deep brain stimulation of the nucleus accumbens reduces alcohol intake in alcohol
      preferring rats.
AB  - OBJECT: The authors tested the hypothesis that deep brain stimulation (DBS) in
      the nucleus accumbens (NAcc) decreases alcohol intake in alcohol-preferring (P)
      rats after each animal has established a stable, large alcohol intake and after P
      rats with an established intake have been deprived of alcohol for 4-6 weeks.
      METHODS: Bipolar stimulating electrodes were bilaterally placed in the NAcc using
      stereotactic coordinates. In the first study, P rats (9 animals) were allowed to
      establish a stable pattern of alcohol intake (about 5-7 g/day) over approximately
      2 weeks, and the acute effects of DBS in the NAcc (140-150 Hz, 60-microsec pulse
      width, and 200-microA current intensity) on alcohol intake and alcohol preference
      were studied. Each animal acted as its own control and received 1 hour of DBS
      followed by 1 hour of sham-DBS or vice versa on each of 2 sequential days. The
      order of testing (sham-DBS vs DBS) was randomized. In the second study, each
      animal was allowed to establish a stable alcohol intake and then the animal was
      deprived of alcohol for 4-6 weeks. Animals received DBS (6 rats) or sham-DBS (5
      rats) in the NAcc for 24 hours starting when alcohol was reintroduced to each
      animal. RESULTS: Deep brain stimulation in the NAcc, as compared with a period of
      sham-DBS treatment in the same animals, acutely decreased alcohol preference.
      Furthermore, alcohol consumption and preference were significantly reduced in the
      DBS group compared with the sham treatment group during the first 24 hours that
      alcohol was made available after a period of forced abstinence. CONCLUSIONS: The
      NAcc plays a key role in the rewarding and subsequent addictive properties of
      drugs of abuse in general and of alcohol in particular. Deep brain stimulation in
      the NAcc reduced alcohol consumption in P rats both acutely and after a period of
      alcohol deprivation. Therefore, DBS in the NAcc coupled with other
      neurophysiological measurements may be a useful tool in determining the role of
      the NAcc in the mesocorticolimbic reward circuit. Deep brain stimulation in the
      NAcc may also be an effective treatment for reducing alcohol consumption in
      patients who abuse alcohol and have not responded to other forms of therapy.

PMID- 20672915
TI  - Deep brain stimulation of the posteromedial hypothalamus: indications, long-term
      results, and neurophysiological considerations.
AB  - OBJECT: The aim of this study was to review the indications for and results of
      deep brain stimulation (DBS) of the posterior hypothalamus (pHyp) in the
      treatment of drug-refractory and severe painful syndromes of the face, disruptive
      and aggressive behavior associated with epilepsy, and below-average intelligence.
      The preoperative clinical picture, functional imaging studies, and overall
      clinical results in the literature are discussed. METHODS: All patients underwent
      stereotactic implantation of deep-brain electrodes within the pHyp. Data from
      several authors have been collected and reported for each clinical entity, as
      have clinical results, adverse events, and neurophysiological characteristics of
      the pHyp. RESULTS: The percentage of patients with chronic cluster headache who
      responded to DBS was 50% in the overall reported series. The response rate was
      100% for short-lasting unilateral neuralgiform headache attacks with conjunctival
      injection and tearing and for chronic paroxysmal hemicrania, although only 2
      patients and 1 patient, respectively, have been described as having these
      conditions. None of the 4 patients suffering from refractory neuropathic
      trigeminal pain benefited from the procedure (0% response rate), whereas all 5
      patients (100%) affected with refractory trigeminal neuralgia (TN) due to
      multiple sclerosis (MS) and undergoing pHyp DBS experienced a significant
      decrease in pain attacks within the first branch of cranial nerve V. Six (75%) of
      8 patients presenting with aggressive behavior and mental retardation benefited
      from pHyp stimulation; 6 patients were part of the authors' series and 2 were
      reported in the literature. CONCLUSIONS: In carefully selected patients, DBS of
      the pHyp can be considered an effective procedure for the treatment of refractory
      trigeminal autonomic cephalalgias, aggressive behavior, and MS-related TN in the
      first trigeminal branch. Only larger and prospective studies along with
      multidisciplinary approaches (including, by necessity, neuroimaging studies) can
      lead us to better patient selection that would reduce the rate of nonresponders.

PMID- 20672916
TI  - Deep brain stimulation in the management of disorders of consciousness: a review
      of physiology, previous reports, and ethical considerations.
AB  - Patients suffering from disorders of consciousness constitute a population that
      exists largely outside of the daily practice patterns of neurosurgeons.
      Historically, treatment has focused on nursing and custodial issues with limited
      neurosurgical intervention. Recently, however, deep brain stimulation has been
      explored to restore cognitive and physical function to patients in minimally
      conscious states. In this article, the authors characterize the physiological
      mechanisms for the use of deep brain stimulation in persistently vegetative and
      minimally conscious patients, review published cases and associated ethical
      concerns, and discuss future directions of this technology.

PMID- 20672917
TI  - Deep brain stimulation compared with bariatric surgery for the treatment of
      morbid obesity: a decision analysis study.
AB  - OBJECT: Roux-en-Y gastric bypass is the gold standard treatment for morbid
      obesity, although failure rates may be high, particularly in patients with a BMI
      > 50 kg/m(2). With improved understanding of the neuropsychiatric basis of
      obesity, deep brain stimulation (DBS) offers a less invasive and reversible
      alternative to available surgical treatments. In this decision analysis, the
      authors determined the success rate at which DBS would be equivalent to the two
      most common bariatric surgeries. METHODS: Medline searches were performed for
      studies of laparoscopic adjustable gastric banding (LAGB), laparoscopic Roux-en-Y
      gastric bypass (LRYGB), and DBS for movement disorders. Bariatric surgery was
      considered successful if postoperative excess weight loss exceeded 45% at 1-year
      follow-up. Using complication and success rates from the literature, the authors
      constructed a decision analysis model for treatment by LAGB, LRYGB, DBS, or no
      surgical treatment. A sensitivity analysis in which major parameters were
      systematically varied within their 95% CIs was used. RESULTS: Fifteen studies
      involving 3489 and 3306 cases of LAGB and LRYGB, respectively, and 45 studies
      involving 2937 cases treated with DBS were included. The operative successes were
      0.30 (95% CI 0.247-0.358) for LAGB and 0.968 (95% CI 0.967-0.969) for LRYGB.
      Sensitivity analysis revealed utility of surgical complications in LRYGB,
      probability of surgical complications in DBS, and success rate of DBS as having
      the greatest influence on outcomes. At no values did LAGB result in superior
      outcomes compared with other treatments. CONCLUSIONS: Deep brain stimulation must
      achieve a success rate of 83% to be equivalent to bariatric surgery. This high
      threshold success rate is probably due to the reported success rate of LRYGB,
      despite its higher complication rate (33.4%) compared with DBS (19.4%). The
      results support further research into the role of DBS for the treatment of
      obesity.

PMID- 20672918
TI  - Stimulation of the globus pallidus internus in a patient with DYT1-positive
      primary generalized dystonia: a 10-year follow-up.
AB  - The authors report the case of DYT1-positive primary generalized dystonia
      refractory to medical management that was successfully treated with continuous
      deep brain stimulation of the internal segment of the globus pallidus. Prior
      studies have shown that neuromusculoskeletal deficits can remain permanent if
      early surgical intervention is not undertaken. The authors report prolonged
      efficacy and safety over a 10-year period in a 28-year-old man.

PMID- 20672919
TI  - Current and future indications for deep brain stimulation in pediatric
      populations.
AB  - Deep brain stimulation (DBS) has proven to be an effective and safe treatment
      option in patients with various advanced and treatment-refractory conditions.
      Thus far, most of the experience with DBS has been in the movement disorder
      literature, and more specifically in the adult population, where its use in
      conditions such as Parkinson disease has revolutionized management strategies.
      The pediatric population, however, can also be afflicted by functionally
      incapacitating neurological conditions that remain refractory despite the
      clinicians' best efforts. In such cases, DBS offers an additional treatment
      alternative. In this paper, the authors review their institution's experience
      with DBS in the pediatric population, and provide an overview of the literature
      on DBS in children. The authors conclude that DBS in children can and should be
      considered a valid and effective treatment option, albeit in highly specific and
      carefully selected cases.

PMID- 20672920
TI  - Best surgical practices: a stepwise approach to the University of Pennsylvania
      deep brain stimulation protocol.
AB  - Deep brain stimulation (DBS) is the treatment of choice for otherwise healthy
      patients with advanced Parkinson disease who are suffering from disabling
      dyskinesias and motor fluctuations related to dopaminergic therapy. As DBS is an
      elective procedure, it is essential to minimize the risk of morbidity. Further,
      precision in targeting deep brain structures is critical to optimize efficacy in
      controlling motor features. The authors have already established an operational
      checklist in an effort to minimize errors made during DBS surgery. Here, they set
      out to standardize a strict, step-by-step approach to the DBS surgery used at
      their institution, including preoperative evaluation, the day of surgery, and the
      postoperative course. They provide careful instruction on Leksell frame assembly
      and placement as well as the determination of indirect coordinates derived from
      MR images used to target deep brain structures. Detailed descriptions of the
      operative procedure are provided, outlining placement of the stereotactic arc as
      well as determination of the appropriate bur hole location, lead placement using
      electrophysiology, and placement of the internal pulse generator. The authors
      also include their approach to preventing postoperative morbidity. They believe
      that a strategic, step-by-step approach to DBS surgery combined with a
      standardized checklist will help to minimize operating room mistakes that can
      compromise targeting and increase the risk of complication.

PMID- 20672921
TI  - Relationship between higher rates of adverse events in deep brain stimulation
      using standardized prospective recording and patient outcomes.
AB  - OBJECT: Adverse event (AE) rates for deep brain stimulation (DBS) are variable,
      due to various methodologies used for identifying, collecting, and reporting AEs.
      This lack of a prospective, standardized AE collection method is a shortcoming in
      the advancement of DBS. In this paper the authors disclose the standardized and
      prospectively recorded AE data from their institution, correlated with clinical
      outcome and quality of life (QOL) measures. METHODS: All patients who underwent
      operations at the authors' institution for Parkinson disease (PD), essential
      tremor, dystonia, other tremor, and obsessive-compulsive disorder were included.
      Complications occurring intraoperatively or within the first 180 days following
      surgery were recorded, analyzed, and classified as mild, moderate, or severe,
      regardless of their perceived relationship to the procedure. The presence,
      frequency, and severity of AEs were compared with the following outcome
      measurements: postoperative change in the QOL scales (Medical Outcomes Study 36
      Item Short-Form Survey, 39-Item PD Questionnaire); motor scales (Tremor Rating
      Scale, Unified Dystonia Rating Scale, Unified PD Rating Scale); and Patient
      Global Impression Scale (PGIS). RESULTS: Two hundred seventy DBS procedures were
      performed in 198 patients. Three hundred AEs were recorded in 146 (54.1%) of the
      270 procedures, and the AEs were recorded in 119 (60.1%) of 198 patients. Of the
      198 patients, the maximum severity of AEs was mild in 28 (14.1%), moderate in 35
      (17.7%), and severe in 56 (28.3%). Of the 300 AEs, 102 (34.1%) of 299 were mild,
      106 (35.5%) were moderate, and 91 (30.4%) were severe. The AEs were classified as
      probably not stimulation induced in 10 (3.4%) of 297, probably in 44 (14.9%),
      unclear for 89 (30%), and not applicable to stimulation in 154 (51.9%). Adverse
      events were also classified as probably related to surgery in 111 (37.2%) of 298,
      possibly related in 96 (32.2%), and probably not related to surgery in 91
      (30.5%). There was no significant difference (p = 0.22) in QOL outcomes among
      patients who had no AEs compared with those who experienced mild, moderate, or
      severe AEs. There was no significant difference in QOL outcomes between patients
      who did not experience an AE compared with those who experienced any AE. There
      was no significant difference in the mean General PGIS score between patients
      without an AE versus those with any AE, as well as on the Symptom-Specific PGIS.
      Motor function outcomes did not vary between patients with or without AEs. For
      patients with PD with or without AEs, there was no significant difference in
      preoperative off-medicine Unified PD Rating Scale score and postoperative 6-month
      on-medication/on-stimulation change scores (p = 0.59). For patients with tremor
      there were no differences between those with or without AEs on the Tremor Rating
      Scale for motor function or activities of daily living. Patients with dystonia
      with and without AEs showed no differences in the Unified Dystonia Rating Scale.
      CONCLUSIONS: Prospectively and systematically recording AEs may result in higher
      AE rates, but this does not correlate with poorer QOL, motor function, or patient
      oriented outcome scores.

PMID- 20672922
TI  - Long-term follow-up of deep brain stimulation for Meige syndrome.
AB  - OBJECT: Meige syndrome is characterized by blepharospasm, cervical dystonia, and
      facial oromandibular dystonia. The medical treatment of this condition is largely
      unsuccessful over time and is a major source of decreased quality of life in
      those patients suffering from this disease. Recent advances in the application of
      deep brain stimulation (DBS) surgery techniques for many disorders have prompted
      several recent reports of DBS for medically refractory cases of Meige syndrome.
      While the etiology for this disorder is unknown, it is considered by many
      investigators to be a form of idiopathic torsion dystonia. Pallidal stimulation
      is widely considered to be effective for dystonia. METHODS: The authors report
      the long-term results of bilateral globus pallidus internus (GPi) or subthalamic
      nucleus (STN) stimulation in 3 patients with Meige syndrome and 1 patient with
      Parkinson disease and associated craniofacial dystonia treated at their center.
      RESULTS: Initial 12-month and long-term follow-up Burke-Fahn-Marsden scores were
      substantially improved in all 4 patients compared with preoperative scores.
      CONCLUSIONS: Bilateral GPi DBS may be an effective and safe treatment for
      medically refractory Meige syndrome. The results are comparable with those
      reported in the literature. Sustained and long-term improvement in symptoms does
      appear to be reproducible across reports. The authors' patient with Parkinson
      disease and associated craniofacial dystonia syndrome undergoing bilateral STN
      DBS noted immediate and sustained improvement in his symptoms. Further study is
      required, but these results, along with the other reports, suggest that bilateral
      GPi DBS is an effective treatment for medically refractory Meige syndrome.

PMID- 20672923
TI  - Development of intraoperative electrochemical detection: wireless instantaneous
      neurochemical concentration sensor for deep brain stimulation feedback.
AB  - Deep brain stimulation (DBS) is effective when there appears to be a distortion
      in the complex neurochemical circuitry of the brain. Currently, the mechanism of
      DBS is incompletely understood; however, it has been hypothesized that DBS evokes
      release of neurochemicals. Well-established chemical detection systems such as
      microdialysis and mass spectrometry are impractical if one is assessing changes
      that are happening on a second-to-second time scale or for chronically used
      implanted recordings, as would be required for DBS feedback. Electrochemical
      detection techniques such as fast-scan cyclic voltammetry (FSCV) and amperometry
      have until recently remained in the realm of basic science; however, it is
      enticing to apply these powerful recording technologies to clinical and
      translational applications. The Wireless Instantaneous Neurochemical
      Concentration Sensor (WINCS) currently is a research device designed for human
      use capable of in vivo FSCV and amperometry, sampling at subsecond time
      resolution. In this paper, the authors review recent advances in this
      electrochemical application to DBS technologies. The WINCS can detect dopamine,
      adenosine, and serotonin by FSCV. For example, FSCV is capable of detecting
      dopamine in the caudate evoked by stimulation of the subthalamic
      nucleus/substantia nigra in pig and rat models of DBS. It is further capable of
      detecting dopamine by amperometry and, when used with enzyme linked sensors, both
      glutamate and adenosine. In conclusion, WINCS is a highly versatile instrument
      that allows near real-time (millisecond) detection of neurochemicals important to
      DBS research. In the future, the neurochemical changes detected using WINCS may
      be important as surrogate markers for proper DBS placement as well as the sensor
      component for a "smart" DBS system with electrochemical feedback that allows
      automatic modulation of stimulation parameters. Current work is under way to
      establish WINCS use in humans.

PMID- 20672924
TI  - Disrupting abnormal electrical activity with deep brain stimulation: is epilepsy
      the next frontier?
AB  - Given the tremendous success of deep brain stimulation (DBS) for the treatment of
      movement and neuropsychiatric disorders, clinicians have begun to open up to the
      possible use of electrical stimulation for the treatment of patients with
      uncontrolled seizures. This process has resulted in the discovery of a wide array
      of DBS targets, including the cerebellum, hypothalamus, hippocampus, basal
      ganglia, and various thalamic nuclei. Despite the ambiguity of the mechanism of
      action and the unknowns surrounding potentially ideal stimulation settings,
      several recent trials have empirically demonstrated reasonable efficacy in
      selected cases of medication-refractory seizures. These exciting results have
      fueled a number of studies aimed at firmly establishing DBS as an effective
      treatment for selected cases of intractable epilepsy, and many companies are
      aiming at Food and Drug Administration approval. We endeavor to review the
      studies in the context of the various DBS targets and their relevant circuitry
      for epilepsy. Based on the unfolding research, DBS has the potential to play an
      important role in treating refractory epilepsy. The challenge, as in movement
      disorders, is to assemble interdisciplinary teams to screen, implant, and follow
      patients, and to clarify patient selection. The future will undoubtedly be filled
      with optimization of targets and stimulation parameters and the development of
      best practices. With tailored therapeutic approaches, epilepsy patients have the
      potential to improve with DBS.

PMID- 20672925
TI  - Cerebellar stimulation in the management of medically intractable epilepsy: a
      systematic and critical review.
AB  - OBJECT: The wide application of deep brain stimulation in the management of
      movement as well as other degenerative neurological and psychiatric disorders has
      renewed the interest in using deep brain stimulation in the management of
      medically intractable epilepsy. Various stimulation targets have been used with
      significantly varying results in aborting seizure activity. Electrical cerebellar
      stimulation (CS) has been used for more than 50 years in the management of
      epilepsy, with conflicting results. In the current study, the authors review the
      pertinent literature to outline the role of CS in the management of medically
      refractory epilepsy. METHODS: The PubMed medical database was systematically
      searched for the following terms: "cerebellar," "epilepsy," "stimulation," and
      "treatment," and all their combinations. Case reports were excluded from this
      study. RESULTS: The pertinent articles were categorized into 2 large groups:
      animal experimental and human clinical studies. Particular emphasis on the
      following aspects was given when reviewing the human clinical studies: their
      methodological characteristics, the number of participants, their seizure types,
      the implantation technique and its associated complications, the exact
      stimulation target, the stimulation technique, the seizure outcome, and the
      patients' psychological and social poststimulation status. Three clinical double
      blind studies were found, with similar implantation surgical technique,
      stimulation target, and stimulation parameters, but quite contradictory results.
      Two of these studies failed to demonstrate any significant seizure reduction,
      whereas the third one showed a significant poststimulation decrease in seizure
      frequency. All possible factors responsible for these differences in the findings
      are analyzed in the present study. CONCLUSIONS: Cerebellar stimulation seems to
      remain a stimulation target worth exploring for defining its potential in the
      treatment of medically intractable epilepsy, although the data from the double
      blind clinical studies that were performed failed to establish a clear benefit in
      regard to seizure frequency. A large-scale, double-blind clinical study is
      required for accurately defining the efficacy of CS in epilepsy treatment.

PMID- 20672926
TI  - Criteria for the ethical conduct of psychiatric neurosurgery clinical trials.
AB  - There is an urgent need for an effective therapy for treatment-refractory mental
      illness. Trials ongoing globally that explore surgical treatment, such as deep
      brain stimulation, for refractory psychiatric disease have produced some
      promising early results. However, diverse inclusion criteria and variable
      methodological and ethical standards, combined with the sordid past of
      neuromodulation, confound trial interpretation and threaten the integrity of a
      new and emerging science. What is required is a standard of ethical practice,
      globally applied, for neurosurgical trials in psychiatry that protects patients
      and maintains a high ethical benchmark for clinicians and researchers to meet.
      With mental illness, as well as treatment resistance, reaching epidemic
      proportions, ethically and scientifically sound clinical trials will lead to
      effective and safe surgical treatments that will become vital components of the
      clinicians' armamentarium. Ethical criteria, such as the ones proposed here, need
      to be established now and applied in earnest if the field is to move forward and
      if patients with no other therapeutic options are to receive much-needed
      treatment.

PMID- 20672928
TI  - Deep brain stimulation: the spectrum of application.

PMID- 20672929
TI  - Pediatric neurosurgery during Operation Enduring Freedom.
AB  - OBJECT: Operation Enduring Freedom (OEF) is the current US military conflict
      against terrorist elements in Afghanistan. Deepening US involvement in this
      conflict and increasing coalition casualties prompted the establishment of
      continuous neurosurgical assets at Craig Joint Theater Hospital (CJTH) at Bagram
      Airfield, Afghanistan, in September 2007. As part of the military's medical
      mission, children with battlefield-related injuries and, on a selective case-by
      case basis, non-war-related pathological conditions are treated at CJTH. METHODS:
      A prospectively maintained record was created in which all rotating neurosurgeons
      at CJTH recorded their personal procedures. From this record, the authors were
      able to extract all cases involving patients 18 years of age or younger.
      Variables recorded included: age, sex, and category of patient (for example,
      local national, enemy combatant), date, indication and description of the
      neurosurgical procedure, mechanism of injury, and in-hospital morbidity and
      mortality data. RESULTS: From September 2007 to October 2009, 296 neurosurgical
      procedures were performed at CJTH. Fifty-seven (19%) were performed in 43
      pediatric patients (16 girls and 27 boys) with an average age of 7.5 years (range
      11 days-18 years). Thirty-one of the 57 procedures (54%) were for battlefield
      related trauma and 26 for humanitarian reasons (46%). The vast majority of cases
      were cranial (49/57, 86%) compared with spinal (7/54, 13%), with one peripheral
      nerve case. Craniotomies or craniectomies for penetrating brain injuries were the
      most common procedures. There were 5 complications (11.6%) and 4 in-hospital
      deaths (9.3%). CONCLUSIONS: As in previous military conflicts, children are the
      unfortunate victims of the current Afghanistan campaign. Extremely limited
      pediatric neurosurgical service and care is rendered under challenging conditions
      and Air Force neurosurgeons provide valuable, life-saving pediatric treatment for
      both war-related injuries and humanitarian needs. As the conflict in Afghanistan
      continues, military neurosurgeons will continue to care for injured children to
      the best of their abilities.

PMID- 20672930
TI  - Gene therapy for late infantile neuronal ceroid lipofuscinosis: neurosurgical
      considerations.
AB  - OBJECT: The authors conducted a phase I study of late infantile neuronal ceroid
      lipofuscinosis using an adenoassociated virus serotype 2 (AAV2) vector containing
      the deficient CLN2 gene (AAV2(CU)hCLN2). The operative technique, radiographic
      changes, and surgical complications are presented. METHODS: Ten patients with
      late infantile neuronal ceroid lipofuscinosis disease each underwent infusion of
      AAV2(CU)hCLN2 (3 x 10(12) particle units) into 12 distinct cerebral locations (2
      depths/bur hole, 75 minutes/infusion, and 2 microl/minute). Innovative surgical
      techniques were developed to overcome several obstacles for which little or no
      established techniques were available. Successful infusion relied on preoperative
      stereotactic planning to optimize a parenchymal target and diffuse
      administration. Six entry sites, each having 2 depths of injections, were used to
      reduce operative time and enhance distribution. A low-profile rigid fixation
      system with 6 integrated holding arms was utilized to perform simultaneous
      infusions within a practical time frame. Dural sealant with generous irrigation
      was used to avoid CSF egress with possible subdural hemorrhage or altered
      stereotactic registration. RESULTS: Radiographically demonstrated changes were
      seen in 39 (65%) of 60 injection sites, confirming localization and infusion.
      There were no radiographically or clinically defined complications. CONCLUSIONS:
      The neurosurgical considerations and results of this study are presented to offer
      guidance and a basis for the design of future gene therapy or other clinical
      trials in children that utilize direct therapeutic delivery.

PMID- 20672931
TI  - Germ cell tumors.

PMID- 20672932
TI  - Surgical management of primary central nervous system germ cell tumors:
      proceedings from the Second International Symposium on Central Nervous System
      Germ Cell Tumors.
AB  - The successful treatment of children with a primary CNS germ cell tumor can be
      greatly influenced by the neurosurgeon involved in the diagnostic and therapeutic
      care of these children. Variability in surgical philosophies no doubt exists due
      to the relatively infrequent incidence of these tumors, a lack of consensus
      regarding diagnostic and therapeutic approaches, and the advent of recent
      surgical innovations. Many of these issues were discussed at the Second
      International Symposium on Central Nervous System Germ Cell Tumors through
      presented abstracts and invited presentations. The neurosurgical aspects of these
      proceedings are summarized here in an effort to present the agreed-upon and
      debated issues that may confront the pediatric neurosurgeon.

PMID- 20672933
TI  - Evaluation of intracranial cerebrospinal fluid cytology in staging pediatric
      medulloblastomas, supratentorial primitive neuroectodermal tumors, and
      ependymomas.
AB  - OBJECT: The objective of this study was to determine the role of intracranial CSF
      examination in detecting true cases of early tumor dissemination. Cerebrospinal
      fluid dissemination is an ominous feature of pediatric brain tumors, occurring in
      as many as 30% of medulloblastomas, 25% of supratentorial primitive
      neuroectodermal tumors (PNETs), and 5% of ependymomas at diagnosis. Detecting
      early dissemination is important for determining both treatment and prognosis.
      Dissemination can be detected by evaluating imaging of the full neuraxis and by
      examining CSF cytology. Neuraxis MR imaging and lumbar CSF cytology evaluation
      are widely accepted methods for determining dissemination. However, the value of
      examining intracranial CSF cytology in detecting early dissemination is
      uncertain. METHODS: Under an institutional review board-approved protocol,
      medical records, pathology reports, and radiology reports for 150 patients who
      had undergone resection of brain tumors (88 with medulloblastomas, 21 with
      supratentorial PNETs, and 41 with ependymomas) and who had been evaluated using
      neuraxis MR imaging studies in the last 15 years were retrospectively reviewed.
      Radiology results were compared with the CSF cytology results and long-term
      disease outcomes. RESULTS: Between lumbar and intracranial CSF cytology results,
      7 of 40 were discordant: in 2 intracranial CSF was negative and lumbar CSF was
      positive, and in 5 the reverse was true. The discordance percentage was 18%, with
      a kappa statistic of 0.36. Between MR imaging and lumbar CSF cytology results, 11
      of 65 were discordant: in 9 the lumbar CSF was negative and MR imaging was
      positive, and in 2 the reverse was true. The discordance percentage is 17%, with
      a kappa statistic of 0.27. Between MR imaging and intracranial CSF cytology
      results, 8 of 52 were discordant: in 3 intracranial CSF was negative and MR
      imaging was positive, and in 5 the reverse was true. The discordance rate was
      15%, with a kappa statistic of 0.41. Patients with positive and negative results
      on perioperative neuraxis MR imaging studies had a median survival of 26.8 and
      33.1 months, respectively (p = 0.02). Patients with positive and negative results
      on perioperative lumbar CSF cytology had a median survival of 20.1 and 31.4
      months, respectively (p = 0.11). Patients with positive and negative results on
      intracranial CSF cytology had a median survival of 31 and 31.4 months,
      respectively (p = 0.84). CONCLUSIONS: Discordance exists between the results of
      neuraxis MR imaging and lumbar and intracranial CSF cytology in perioperative
      detection of tumor dissemination for pediatric medulloblastoma, supratentorial
      PNETs, and ependymoma. In 1 case in this series, perioperative dissemination was
      detected by intracranial CSF cytology, but not by lumbar CSF cytology or neuraxis
      MR imaging. Isolated intracranial CSF cytology positivity may represent an
      earlier stage of disseminated disease. Complementary use of perioperative
      neuraxis MR imaging and lumbar and intracranial CSF cytology can reduce the
      incidence of missed diagnoses of dissemination. Survival analysis revealed that
      perioperative neuraxis MR imaging findings are correlated with survival, whereas
      perioperative lumbar and intracranial CSF cytology findings are not.

PMID- 20672934
TI  - Ependymoma of the spinal cord in children and adolescents: a retrospective series
      from the HIT database.
AB  - OBJECT: Reports on spinal cord ependymoma in children are rare. The aim of this
      study was to evaluate the clinical spectrum, treatment, and outcome of children
      with primary ependymoma of the spinal cord who were registered in the database of
      the pediatric German brain tumor studies Hirntumor (HIT) '91 and HIT 2000.
      METHODS: Between 1991 and 2007, 29 patients (12 male and 17 female, median age at
      diagnosis 13.6 years) with primary spinal cord ependymoma (myxopapillary
      ependymoma WHO Grade I, II, and III tumors in 6, 17, and 6 patients,
      respectively) were identified. Four patients had neurofibromatosis Type 2.
      RESULTS: With a median follow-up of 4.2 years (range 0.48-15 years), 28 patients
      (96.6%) were alive. Seven patients (24.1%) developed progressive disease or
      relapse, 2 after gross-total resection (GTR) and 5 after incomplete resection or
      biopsy. One patient with anaplastic ependymoma (WHO Grade III) died 65 months
      after diagnosis of disease progression. Primary adjuvant treatment (radiotherapy,
      chemotherapy, or both) was used in 8 (50%) of 16 patients following GTR and in 9
      (82%) of 11 patients who underwent less than a GTR. Three additional patients
      were treated adjuvantly following progression. Estimated progression-free
      survival and overall survival rates at 5 years were 72.3% (95% CI 50%-86%) and
      100%, respectively. Progression-free survival at 5 years is 84.4% (95% CI 50%
      96%) for patients following GTR compared with 57.1% (95% CI 25%-69%) for patients
      who achieved a less than GTR (p = 0.088, log-rank test). A high relapse incidence
      (4 of 6) was observed among patients with myxopapillary ependymoma. CONCLUSIONS:
      Gross-total resection is the mainstay of treatment for patients with primary
      spinal cord ependymoma and may be achieved in about 50% of the patients using
      modern surgical techniques. Primary adjuvant treatment was commonly used in
      children with spinal cord ependymoma irrespective of the extent of resection or
      tumor grade. The impact of adjuvant treatment on progression-free and overall
      survival has to be investigated in a prospective trial.

PMID- 20672935
TI  - Long-term outcomes in children with glioblastoma.
AB  - OBJECT: Glioblastoma is the most common primary malignant brain tumor; however,
      glioblastoma in children is less common than in adults, and little is known about
      its clinical outcome in children. The authors evaluated the long-term outcome of
      glioblastoma in children. METHODS: Twenty-seven children were confirmed to have
      harbored a glioblastoma between 1985 and 2007. The clinical features and
      treatment outcomes were reviewed retrospectively. All patients underwent
      resection; complete resection was performed in 12 patients (44%), subtotal
      resection in 12 patients (44%), and biopsy in 3 patients (11%). Twenty-four
      patients (89%) had radiation therapy, and 14 (52%) patients received chemotherapy
      plus radiation therapy. Among the latter, 5 patients had radiation therapy
      concurrent with temozolomide chemotherapy. Four patients with small-size
      recurrent glioblastoma received stereotactic radiosurgery. RESULTS: The median
      overall survival (OS) was 43 months, and the median progression-free survival was
      12 months. The OS rate was 67% at 1 year, 52% at 2 years, and 40% at 5 years. The
      median OS was significantly associated with tumor location (52 months for
      superficially located tumors vs 7 months for deeply located tumors; p = 0.017)
      and extent of removal (106 months for completely resected tumors vs 11 months for
      incompletely resected tumors; p < 0.0001). CONCLUSIONS: The prognosis of
      glioblastoma is better in children than in adults. Radical resection followed by
      concurrent chemoradiation therapy may be the initial treatment of choice.

PMID- 20672936
TI  - A ruptured middle cerebral artery aneurysm in a 13-month-old boy with Kawasaki
      disease.
AB  - This 13-month-old boy, in whom Kawasaki disease had been diagnosed at the age of
      6 months, presented with subarachnoid hemorrhage caused by the rupture of a
      middle cerebral artery aneurysm. The authors performed an emergency craniectomy
      and clip occlusion of the aneurysm, which was found to be partially thrombosed.
      The patient was discharged 4 weeks postoperatively without apparent neurological
      deficit. Intracranial saccular aneurysms in the pediatric population are rare,
      and are occasionally associated with various systemic disorders. Kawasaki disease
      is a systemic vasculopathy of unknown origin, but cerebral arteries are usually
      spared from the disease process. This is the second case report of a ruptured
      cerebral aneurysm in a patient with Kawasaki disease, providing a novel clinical
      feature that the authors call Kawasaki syndrome.

PMID- 20672937
TI  - Stent placement for the treatment of a symptomatic intracranial arterial
      dissection in an adolescent.
AB  - Intracranial arterial dissection is an important cause of stroke in young
      patients. Treatment options include observation, antiplatelet or anticoagulation
      regimens, and endovascular stent placement. The authors describe the case of a 14
      year-old boy who presented with a symptomatic, posttraumatic dissection extending
      from the intracranial internal carotid artery to the middle cerebral artery.
      Images obtained approximately 48 hours after this incident revealed a subacute
      right frontal lobe infarct, and a CT stroke study (CT angiography and CT
      perfusion) confirmed the vascular injury and associated decreased perfusion,
      prompting revascularization with a self-expanding stent. The patient did well
      clinically after stent placement and showed no evidence of restenosis on follow
      up angiography 3 and 6 months later. This report is, to the authors' knowledge,
      the first description of the use of a stent for a symptomatic intracranial
      dissection in an adolescent.

PMID- 20672938
TI  - Alterations of pulsation absorber characteristics in experimental hydrocephalus.
AB  - OBJECT: Analysis of waveform data in previous studies suggests that the pulsatile
      movement of CSF may play a role in attenuating strong arterial pulsations
      entering the cranium, and its effectiveness in attenuating these pulsations may
      be altered by changes in intracranial pressure (ICP). These findings were
      obtained in studies performed in canines with normal anatomy of the CSF spaces.
      How then would pulsation absorbance respond to changes in CSF movement under
      obstructive conditions such as the development of hydrocephalus? In the present
      study, chronic obstructive hydrocephalus was induced by the injection of
      cyanoacrylate gel into the fourth ventricle of canines, and pulsation absorbance
      was compared before and after hydrocephalus induction. METHODS: Five animals were
      evaluated with simultaneous recordings of ICP and arterial blood pressure (ABP)
      before and at 4 and 12 weeks after fourth ventricle obstruction by cyanoacrylate.
      To assess how the intracranial system responds to the arterial pulsatile
      component, ABP and ICP waveforms recorded in a time domain had to be analyzed in
      a frequency domain. In an earlier study the authors introduced a particular
      technique that allows characterization of the intracranial system in the
      frequency domain with sufficient accuracy and efficiency. This same method was
      used to analyze the relationship between ABP and ICP waveforms recorded during
      several acute states including hyperventilation as well as CSF withdrawal and
      infusion under conditions before and after inducing chronic obstructive
      hydrocephalus. Such a relationship is reflected in terms of a gain, which is a
      function of frequency. The cardiac pulsation absorbance (CPA) index, which is
      simply derived from a gain evaluated at the cardiac frequency, was used to
      quantitatively evaluate the changes in pulsation absorber function associated
      with the development of hydrocephalus within each of the animals, which did
      become hydrocephalic. To account for normal and hydrocephalic conditions within
      the same animal and at multiple time points, statistical analysis was performed
      by repeated-measures ANOVA. RESULTS: The performance of the pulsation absorber as
      assessed by CPA significantly deteriorated after the development of chronic
      hydrocephalus. In these animals the decrement in CPA was far more significant
      than other anticipated changes including those in ICP, compliance, or ICP pulse
      amplitude. CONCLUSIONS: To the extent that the free CSF movement acts as a buffer
      of arterial pulsation input to flow in microvessels, alterations in the pulsation
      absorber may play a pathophysiological role. One measure of alterations in the
      way the brain deals with pulsatile input-the CPA measurement-changes dramatically
      with the imposition of hydrocephalus. Results in the present study suggest that
      CPA may serve as a complementary metric to the conventional static measure of
      intracranial compliance in other experimental and clinical studies.

PMID- 20672939
TI  - Placement of occipital condyle screws for occipitocervical fixation in a
      pediatric patient with occipitocervical instability after decompression for
      Chiari malformation.
AB  - In cadaveric studies and recently in one adult patient the occipital condyle has
      been studied as an option to allow bone purchase by fixation devices. In the
      current case the authors describe the use of occipital condyle screws in a child
      undergoing occipitocervical fixation. To the best of the authors' knowledge this
      case is the first reported instance of this technique in a pediatric patient.
      This girl had a history of posterior fossa decompression for Chiari malformation
      Type I when she was 22 months of age. When she was 6 years old she presented with
      neck pain on flexion and extension of her head. Magnetic resonance imaging in
      flexion and extension revealed occipitocervical instability. She underwent an
      occiput to C-2 posterior arthrodesis with bilateral screw placement in the
      occipital condyles, C-2 lamina, and C-1 lateral masses. Postoperatively, she was
      neurologically intact. Computed tomography demonstrated a stable construct, and
      her cervical pain had resolved on follow-up.

PMID- 20672940
TI  - Prevalence of tethered spinal cord in infants with VACTERL.
AB  - OBJECT: The term VACTERL represents a nonrandom association of birth defects
      including vertebral malformations, anal atresia, cardiac anomalies,
      tracheoesophageal fistulas (TEFs), renal anomalies, and limb malformations.
      Clinical experience and a few published case series suggest that a tethered
      spinal cord (TSC) occurs commonly in children with VACTERL, but to date, no study
      has defined the prevalence of TSC in patients with VACTERL. Such information
      would guide decisions about the appropriateness of screening spinal imaging.
      METHODS: The authors reviewed the charts of all patients discharged from the
      neonatal intensive care unit at Children's Hospital Pittsburgh in the past 14
      years with the diagnosis of VACTERL, TEF, or anal atresia. During that period,
      the authors' protocol has been to use spinal ultrasound to screen this population
      for TSC. The charts were reviewed for the presence of a TSC requiring surgery and
      for the features of VACTERL. RESULTS: Thirty-three patients with VACTERL and
      adequate spinal imaging studies were identified. In 13 (39%) of these, a TSC
      requiring surgery was identified. Among patients without VACTERL, the incidence
      of TSC was 7.9% in those with anal atresia and 2.4% in those with TEF. False
      negative ultrasounds were identified in 21.4% of patients with TSC. CONCLUSIONS:
      Children with VACTERL should undergo MR imaging screening for TSC. In infants
      with anal atresia without VACTERL, the incidence of TSC is much lower than in
      those with VACTERL.

PMID- 20672941
TI  - Biportal thoracoscopic sympathectomy for palmar hyperhidrosis in adolescents.
AB  - OBJECT: Palmar, axillary, and plantar hyperhidrosis is often socially,
      emotionally, and physically disabling for adolescents. The authors report
      surgical outcomes in all adolescents treated for palmar hyperhidrosis via
      bilateral thoracoscopic sympathectomy at the Barrow Neurological Institute by the
      senior author. METHODS: A prospectively maintained database of all adolescent
      patients undergoing bilateral thoracoscopic sympathectomy between 1998 and 2006
      (inclusive) was reviewed. Additional follow-up was obtained as needed in clinic
      or by phone or written questionnaire. RESULTS: Fifty-four patients (40 females)
      undergoing bilateral procedures were identified. Their mean age was 15.4 years
      (range 10-17 years). Average follow-up was 42 weeks (range 0.2-143 weeks).
      Hyperhidrosis involved the palms alone in 10 patients; the palms and axilla in 6
      patients; the palms and plantar surfaces in 17 patients; and the palms, axilla,
      and plantar surfaces in 21 patients. Palmar hyperhidrosis resolved completely in
      98.1% of the patients. Resolution or improvement of symptoms was seen in 96.3% of
      patients with axillary and 71.1% of those with plantar hyperhidrosis. Hospital
      stay averaged 0.37 days with 68.5% of patients discharged the day of surgery. One
      patient experienced brief intraoperative asystole that resolved with medications
      and had no long-term sequelae. Otherwise, no serious intraoperative complications
      occurred. No patient required chest tube drainage. The percentage of patients who
      reported satisfaction and willingness to undergo the procedure again was 98.1%.
      CONCLUSIONS: Biportal, bilateral thoracoscopic sympathectomy is an effective and
      low-morbidity treatment for severe palmar, axillary, and plantar hyperhidrosis.

PMID- 20672942
TI  - Endoscopic repair of a rare basioccipital meningocele associated with recurrent
      meningitis.
AB  - Anatomical variants of the basiocciput are uncommon and usually clinically
      benign. While the majority remain undetected, these anomalies rarely manifest as
      CSF rhinorrhea or recurrent meningitis associated with meningocele. Compromise of
      the leptomeninges provides an avenue of ingress for pathological organisms and
      can lead to recurrent meningitis, necessitating operative repair of the defect to
      prevent infection. A review of the literature reveals only 3 cases in which a
      congenital basioccipital defect has been associated with a meningocele requiring
      surgical repair. The authors present a case of recurrent meningitis in an infant
      with a congenital basioccipital meningocele treated with a minimally invasive
      endoscopic technique. At the 2-year follow-up the repair remained successful,
      with no evidence of recurrence of the meningocele or CSF infection. The
      literature regarding the etiology and treatment of these lesions was reviewed,
      with an emphasis on the safety and efficacy of the endoscopic approach. Note that
      recurrent meningitis in the setting of a skull base defect may indicate the
      presence of other congenital anomalies that will necessitate multidisciplinary
      care for a patient's long-term well-being.

PMID- 20672943
TI  - Surgical treatment of single-suture craniosynostosis: an argument for
      quantitative methods to evaluate cosmetic outcomes.
AB  - The traditional reasons for surgical intervention in children with single-suture
      craniosynostosis (SSC) are cosmetic improvement and the avoidance/treatment of
      intracranial hypertension, which has been thought to contribute to neurocognitive
      deficits. Despite considerable work on the topic, the exact prevalence of
      intracranial hypertension in the population of patients with SSC is unknown,
      although it appears to be present in only a minority. Additionally, recent
      neuropsychological and anatomical literature suggests that the subtle
      neurocognitive deficits identified in children with a history of SSC may not
      result from external compression. They may instead reflect an underlying
      developmental condition that includes disordered primary CNS development and
      early suture fusion. This implies that current surgical techniques are unlikely
      to prevent neurocognitive deficits in patients with SSC. As such, the most common
      indication for surgical treatment in SSC is cosmetic, and most patients benefit
      from considerable subjective cosmetic normalization following surgery. Pediatric
      craniofacial surgeons have not, however, agreed upon objective means to assess
      postoperative cranial morphological improvement. We should therefore endeavor to
      agree upon objective craniometric tools for the assessment of operative outcomes,
      allowing us to accurately compare the various surgical techniques that are
      currently available.

PMID- 20672944
TI  - Craniosynostosis in Kabuki syndrome.
AB  - Niikawa-Kuroki, or Kabuki syndrome (KS), is characterized by distinctive facial
      features, skeletal anomalies, persisting fingertip pads with dermatoglyphic
      abnormalities, short stature, and mental retardation. Neurological manifestations
      and CNS anomalies have been described in some patients with this condition.
      However, craniosynostosis has been documented in only 4 patients with KS who did
      not undergo operations. The authors report a case of KS with unicoronal
      synostosis that constitutes the first documented instance of a patient with this
      syndrome submitted to surgery. Previous reported instances of craniosynostosis
      occurring in KS are briefly reviewed. Although rarely documented,
      craniosynostosis might represent a relatively frequent feature of this syndrome.
      Kabuki syndrome should be considered at the time of evaluating children with
      craniosynostosis. The diagnosis of KS can be suspected from the patients'
      characteristic facial features. Kabuki syndrome appears to be an underdiagnosed
      condition in the craniosynostosis population. Given that most patients with this
      syndrome suffer from only mild to moderate mental retardation, surgical
      correction can be considered in instances of KS with craniosynostosis.

PMID- 20672945
TI  - Vacuum extraction.

PMID- 20672948
TI  - Accurate identification of complications in spine surgery: an opportunity for
      excellence.

PMID- 20672949
TI  - Complications in spine surgery.
AB  - OBJECT: The overall incidence of complications or adverse events in spinal
      surgery is unknown. Both prospective and retrospective analyses have been
      performed, but the results have not been critically assessed. Procedures for
      different regions of the spine (cervical and thoracolumbar) and the incidence of
      complications for each have been reported but not compared. Authors of previous
      reports have concentrated on complications in terms of their incidence relevant
      to healthcare providers: medical versus surgical etiology and the relevance of
      perioperative complications to perioperative events. Few authors have assessed
      complication incidence from the patient's perspective. In this report the authors
      summarize the spine surgery complications literature and address the effect of
      study design on reported complication incidence. METHODS: A systematic evidence
      based review was completed to identify within the published literature
      complication rates in spinal surgery. The MEDLINE database was queried using the
      key words "spine surgery" and "complications." This initial search revealed more
      than 700 articles, which were further limited through an exclusion process. Each
      abstract was reviewed and papers were obtained. The authors gathered 105 relevant
      articles detailing 80 thoracolumbar and 25 cervical studies. Among the 105
      articles were 84 retrospective studies and 21 prospective studies. The authors
      evaluated the study designs and compared cervical, thoracolumbar, prospective,
      and retrospective studies as well as the durations of follow-up for each study.
      RESULTS: In the 105 articles reviewed, there were 79,471 patients with 13,067
      reported complications for an overall complication incidence of 16.4% per
      patient. Complications were more common in thoracolumbar (17.8%) than cervical
      procedures (8.9%; p < 0.0001, OR 2.23). Prospective studies yielded a higher
      incidence of complications (19.9%) than retrospective studies (16.1%; p < 0.0001,
      OR 1.3). The complication incidence for prospective thoracolumbar studies (20.4%)
      was greater than that for retrospective series (17.5%; p < 0.0001). This
      difference between prospective and retrospective reviews was not found in the
      cervical studies. The year of study publication did not correlate with the
      complication incidence, although the duration of follow-up did correlate with the
      complication incidence (p = 0.001). CONCLUSIONS: Retrospective reviews
      significantly underestimate the overall incidence of complications in spine
      surgery. This analysis is the first to critically assess differing complication
      incidences reported in prospective and retrospective cervical and thoracolumbar
      spine surgery studies.

PMID- 20672950
TI  - Surgical site infection in spinal surgery: detection and management based on
      serial C-reactive protein measurements.
AB  - OBJECT: C-reactive protein (CRP) is a well-known sensitive laboratory parameter
      that shows an increase within 6 hours after the onset of bacterial infection. In
      relation to surgery, a normal CRP response is a rapid increase followed by a
      gradual reduction, eventually returning to the normal range. The goal of this
      study was to determine the diagnostic significance of CRP as a detector for early
      onset surgical site infection in spinal surgery and to discuss effective medical
      treatment through clinical interpretation and application of the measured CRP
      values. METHODS: A prospective study was performed in 348 consecutive cases
      involving patients who underwent spinal surgery under general anesthesia between
      February and September 2008. Blood samples were obtained preoperatively and on
      postoperative Days 1, 3, and 5 in patients undergoing single-level decompression
      surgery. An additional blood specimen was obtained at postoperative Day 7 in
      patients requiring more extensive surgeries. Recorded laboratory results were
      compared with the patients' clinical course to determine the diagnostic
      significance of CRP. All of the patients received intravenous prophylactic
      antibiotic therapy. Once an abnormal response of CRP, indicated by a tendency
      toward continuous elevation, was noted on Day 5 or Day 7, the prophylactic
      antibiotics were replaced with another regimen and administration was resumed
      along with careful observation for signs of surgical site infection. RESULTS:
      Monitoring of CRP revealed a characteristic increase and decrease pattern in 332
      of 348 patients (95.4%) showing a normal clinical course with regard to early
      infectious complications. The mean measured CRP (reference range < 4 mg/L)
      averaged 14.9 +/- 20.3 mg/L on Day 1, 15.4 +/- 25.1 mg/L on Day 3, and 7.9 +/-
      13.3 mg/L on Day 5. In contrast, there were 16 cases (4.6%) of abnormal CRP
      responses resulting in the resumption of intravenous antibiotic treatment, which
      included a second rise (in 12 cases) and a steady rise (in 4) in the CRP value.
      Five (1.4%) of 16 patients experienced infectious complications related to spinal
      surgery. Three patients (0.9%) received long-term antibiotic therapy for 4-6
      weeks; however, all patients recovered with medical treatment alone and did not
      experience gross wound disruption or subsequent discitis. As a predictor for
      early wound infection, the sensitivity, specificity, positive predictive value,
      and negative predictive value for abnormal CRP responses were calculated as 100%,
      96.8%, 31.3%, and 100%, respectively. CONCLUSIONS: The above results demonstrate
      that CRP screening is a simple and reliable test for the detection of early
      infectious complications after spinal surgery. Close observation and appropriate
      medical management should be performed in a timely fashion when abnormal CRP
      responses are observed at 5 or 7 days after surgery.

PMID- 20672951
TI  - Scarring after spinal cord injury.

PMID- 20672952
TI  - Glial scar and neuroregeneration: histological, functional, and magnetic
      resonance imaging analysis in chronic spinal cord injury.
AB  - OBJECT: A glial scar is thought to be responsible for halting neuroregeneration
      following spinal cord injury (SCI). However, little quantitative evidence has
      been provided to show the relationship of a glial scar and axonal regrowth after
      injury. METHODS: In this study performed in rats and dogs, a traumatic SCI model
      was made using a weight-drop injury device, and tissue sections were stained with
      H & E for immunohistochemical analysis. The function and behavior of model
      animals were tested using electrophysiological recording and the Basso-Beattie
      Bresnahan Locomotor Rating Scale, respectively. The cavity in the spinal cord
      after SCI in dogs was observed using MR imaging. RESULTS: The morphological
      results showed that the formation of an astroglial scar was defined at 4 weeks
      after SCI. While regenerative axons reached the vicinity of the lesion site, the
      glial scar blocked the extension of regrown axons. In agreement with these
      findings, the electrophysiological, behavioral, and in vivo MR imaging tests
      showed that functional recovery reached a plateau at 4 weeks after SCI. The
      thickness of the glial scars in the injured rat spinal cords was also measured.
      The mean thickness of the glial scar rostral and caudal to the lesion cavity was
      107.00 +/- 20.12 microm; laterally it was 69.92 +/- 15.12 microm. CONCLUSIONS:
      These results provide comprehensive evidence indicating that the formation of a
      glial scar inhibits axonal regeneration at 4 weeks after SCI. This study reveals
      a critical time window of postinjury recovery and a detailed spatial orientation
      of glial scar, which would provide an important basis for the development of
      therapeutic strategy for glial scar ablation.

PMID- 20672953
TI  - Lesion growth and degeneration patterns measured using diffusion tensor 9.4-T
      magnetic resonance imaging in rat spinal cord injury.
AB  - OBJECT: Using diffusion tensor MR imaging, the authors conducted a study to
      explore lesion growth and degeneration patterns, from the acute through chronic
      stages of spinal cord injury (SCI), in an experimental animal model. METHODS: In
      vivo and ex vivo diffusion tensor imaging was performed using a 9.4-T MR imaging
      system in rats allowed to recover from traumatic contusion SCI from 2 weeks
      through 25 weeks postinjury, mimicking progression of human SCI from the acute
      through chronic stages. RESULTS: Results showed significant growth of the
      traumatic lesion up to 15 weeks postinjury, where both the size and mean
      diffusivity (MD) reached a maximum that was maintained through the remainder of
      recovery. Mean diffusivity was sensitive to overall spinal cord integrity,
      whereas fractional anisotropy showed specificity to sites of cavity formation.
      The use of an MD contour map for in vivo data and a 3D surface map for ex vivo
      data, showing MD as a function of rostral-caudal distance and recovery time,
      allowed documentation of rostral and caudal spreading of the lesion. CONCLUSIONS:
      Results from this study demonstrate changes in both lesion morphology and
      diffusivity beyond previously reported time points and provide a unique
      perspective on the process of cavity formation and degeneration following
      traumatic SCI. Additionally, results suggest that MD more accurately defines
      regions of histological damage than do regions of T2 signal hyperintensity. This
      could have significant clinical implications in the detection and potential
      treatment of posttraumatic syringes in SCI.

PMID- 20672954
TI  - Impact of cordectomy as a treatment option for posttraumatic and non
      posttraumatic syringomyelia with tethered cord syndrome and myelopathy.
AB  - OBJECT: Spinal cordectomy has recently become more important in the treatment of
      end-stage posttraumatic or postoperative syringomyelia and arachnopathy as a last
      resort to manage ascending neurological dysfunction, spasticity, and pain in
      paraplegic patients. The aim in this study was to confirm a clinical benefit in
      strict indications for cordectomy. METHODS: Between February 2000 and September
      2007, 15 spinal cordectomies were performed at the Department of Neurosurgery,
      Cantonal Hospital, St. Gallen. Indications for treatment were end-stage
      myelopathies caused by syringomyelia, tethered cord syndrome, and arachnopathy
      with progressive spasticity and pain or progressive upper-level neurological
      deficits related to the tethered cord syndrome. All patients had severe motor and
      sensory deficits with no residual voluntary function below the affected level.
      RESULTS: Fourteen of 15 patients showed stabilization or even an improvement in
      motor and sensory function. Four patients suffered from progressive spasticity
      and 3 from deterioration due to pain. There were no other adverse surgical
      events. CONCLUSIONS: Cordectomy can be a useful instrument to preserve functions
      of the upper extremities and to improve spasticity and pain in patients with
      severe myelopathy and tethered cord, syringomyelia, or arachnopathy of various
      etiologies.

PMID- 20672955
TI  - Efficacy and limitations of intraoperative spinal cord monitoring using
      nasopharyngeal tube electrodes.
AB  - OBJECT: Motor evoked potentials are widely used for intraoperative spinal cord
      monitoring. However, there are problems with anesthetic constraints and high
      trial-by-trial variability of compound muscle action potential amplitude in
      muscle motor evoked potential monitoring. It is difficult to determine when to
      warn the surgeon of an occurrence of spinal cord risk. A method of estimation for
      motor function in the spinal cord has not been established. To monitor spinal
      cord function with reliable evoked potentials, including the upper cervical
      spinal cord and the ventral spinal cord, the authors developed a nasopharyngeal
      tube electrode that can be placed in front of the upper and ventral cervical
      spinal cord. The purpose of this study was to investigate the origins and
      pathways of descending or ascending spinal cord evoked potentials (SCEPs)
      elicited with this electrode, and the usefulness and limitations of this method.
      METHODS: A nasopharyngeal tube electrode was inserted into the nostril. A
      catheter electrode was placed in the epidural or subarachnoid space at the
      thoracic spine. Ventral SCEP was recorded from the thoracic spinal cord after
      transpharyngeal stimulation, and dorsal SCEP was recorded with the nasopharyngeal
      electrode after thoracic spinal cord stimulation. There was no restriction of
      anesthetic technique in recording. When the amplitude of either of the SCEPs
      declined to 80% of the baseline, a warning was provided to the surgeon during the
      observed operative procedure. At the end of surgery, less than 50% or more than
      30% of the baseline amplitude was considered a significant change in both SCEPs.
      The sensitivity and specificity for both SCEPs to detect neurological
      deterioration were calculated. RESULTS: The electrode provided noninvasive access
      to the ventral cervicomedullary junction. The SCEPs showed stable responses. A
      response change was only observed in situations involving a risky procedure for
      the spinal cord. Ventral SCEPs showed high sensitivity (73.1%) for identifying
      patients with new neurological deficits or an exacerbation of preexisting
      neurological deficits after surgery, but dorsal SCEPs showed lower sensitivity
      (46.1%) in the total number of cases. Both SCEPs showed high specificities. The
      sensitivities of ventral SCEP, dorsal SCEP, and either SCEP were 100.0%, 50.0%,
      and 100.0% for the upper cervical spinal cord, 33.3%, 0%, and 55.6% for the lower
      cervical spinal cord, and 77.8%, 64.7%, and 88.2% for the thoracic spinal cord.
      CONCLUSIONS: Combined recording of both SCEPs estimated the ventral and dorsal
      white matter function in the spinal cord. Measuring the SCEPs with the
      nasopharyngeal electrode can be another useful approach for upper cervical and
      thoracic spinal cord monitoring. Ventral SCEP was more reliable for monitoring
      postoperative spinal cord function than dorsal SCEP. Ventral SCEP does not
      estimate the gray matter and spinal root functions in the lower cervical spinal
      cord.

PMID- 20672956
TI  - Healos graft carrier with bone marrow aspirate instead of allograft as adjunct to
      local autograft for posterolateral fusion in degenerative lumbar scoliosis: a
      minimum 2-year follow-up study.
AB  - OBJECT: The objective of this study was to examine the efficacy and safety of
      Healos graft carrier with bone marrow aspirate and local autograft compared with
      the results of allograft in patients with lumbar degenerative scoliosis
      undergoing posterolateral fusion. METHODS: Twenty-eight patients with
      degenerative scoliosis underwent posterolateral instrumented fusion and
      decompression. Patients were grouped according to the graft used. Group A
      consisted of 12 cases in which the authors used a Healos graft carrier, bone
      marrow aspirate, and local autograft, and Group B consisted of 16 cases in which
      the authors used cancellous allograft and local autograft. Patients were followed
      for a minimum of 2 years postoperatively in terms of pain (visual analog scale),
      function (Oswestry Disability Index), curve magnitude (Cobb angle), and fusion
      status (plain and dynamic radiographs). The 2 groups did not differ statistically
      significantly (p > 0.05) in age, sex, smoking habits, magnitude of preoperative
      visual analog scale score, Oswestry Disability Index score, Cobb angle, or number
      of levels requiring decompression and fusion. RESULTS: The groups had similar (p
      > 0.05) results in terms of pain, function, curve progression, and fusion rates
      at the 2-year follow-up examination. Radiographic fusion was achieved in all but
      2 cases, 1 in each group, in which the patients were asymptomatic. Patients in
      the allograft group (Group B) showed evidence of fusion earlier than in the
      Healos group (p < 0.05). No toxicity from Healos graft was recorded. CONCLUSIONS:
      The combination of Healos hydroxyapatite sponge and bone marrow aspirate plus
      local allograft had significantly slower fusion rates but equal clinical outcomes
      compared with cancellous allograft plus local autograft when used for
      posterolateral fusion in patients with degenerative lumbar scoliosis.

PMID- 20672957
TI  - Autologous growth factors versus autogenous graft for anterior cervical interbody
      fusion: an in vivo caprine model.
AB  - OBJECT: Using an in vivo caprine model, authors in this study compared the
      efficacy of autologous growth factors (AGFs) with autogenous graft for anterior
      cervical interbody arthrodesis. METHODS: Fourteen skeletally mature Nubian goats
      were used in this study and followed up for a period of 16 weeks postoperatively.
      Anterior cervical interbody arthrodesis was performed at the C3-4 and C5-6
      vertebral levels. Four interbody treatment groups (7 animals in each group) were
      equally randomized among the 28 arthrodesis sites: Group 1, autograft alone;
      Group 2, autograft + cervical cage; Group 3, AGFs + cervical cage; and Group 4,
      autograft + anterior cervical plate. Groups 1 and 4 served as operative controls.
      Autologous growth factors were obtained preoperatively from venous blood and were
      ultra-concentrated. Following the 16-week survival period, interbody fusion
      success was evaluated based on radiographic, biomechanical, and histological
      analyses. RESULTS: All goats survived surgery without incidence of vascular or
      infectious complications. Radiographic analysis by 3 independent observers
      indicated fusion rates ranging from 9 (43%) of 21 in the autograft-alone and
      autograft + cage groups to 12 (57%) of 21 in the autograft + anterior plate
      group. The sample size was not large enough to detect any statistical
      significance in these observed differences. Biomechanical testing revealed
      statistical differences (p < 0.05) between all treatments and the nonoperative
      controls under axial rotation and flexion and extension loading. Although the AGF
      + cage and autograft-alone treatments appeared to be statistically different from
      the intact spine during lateral bending, larger variances and smaller relative
      differences precluded a determination of statistical significance.
      Histomorphometric analysis of bone formation within the predefined fusion zone
      indicated quantities of bone within the interbody cage ranging from 21.3 +/-
      14.7% for the AGF + cage group to 34.5 +/- 9.9% for the autograft-alone group.
      CONCLUSIONS: The results indicated no differences in biomechanical findings among
      the treatment groups and comparable levels of trabecular bone formation within
      the fusion site between specimens treated with autogenous bone and those filled
      with the ultra-concentrated AGF extract. In addition, interbody cage treatments
      appeared to maintain disc space height better than autograft-alone treatments.

PMID- 20672958
TI  - Omovertebral bone associated with Sprengel deformity and Klippel-Feil syndrome
      leading to cervical myelopathy.
AB  - The unusual association of an omovertebral bone with Sprengel deformity and
      Klippel-Feil syndrome is a complex bone anomaly of unknown incidence and
      etiology. However, several cases of this rare disease pattern have been reported
      in the literature. In this paper, the authors present the case of a 34-year-old
      woman with a 5-month history of progressive gait ataxia and intermittent urinary
      incontinence, which was found to be caused by aberrant bone growth into the
      spinal canal from an omovertebral bone that extended from the left scapula
      pressing into the C-6 vertebral arch and subsequently causing cervical
      myelopathy. The patient underwent isolated resection of the omovertebral bone and
      decompression of the spinal canal, and her functional and neurological outcome
      was favorable.

PMID- 20672959
TI  - Midline trough corpectomies for the evacuation of an extensive ventral cervical
      and upper thoracic spinal epidural abscess.
AB  - The author reports on a 59-year-old woman with a history of a chronic, nonhealing
      skin ulcer who presented with sepsis, neck pain, and rapidly progressive
      quadriparesis. Precontrast and postcontrast MR imaging studies revealed a
      multifocal ventral cervical and upper thoracic spinal epidural abscess.
      Compression of the spinal cord from the abscess was greatest behind the disc
      space of C2-3 and C7-T1. Because of the patient's tenuous medical status, the
      author elected to apply a technique that would allow expeditious decompression
      without necessitating concomitant fusion and instrumentation. Multilevel,
      contiguous trough corpectomies were performed for evacuation of the compressive
      lesions. A high-speed matchstick bur was used to create a 5- to 7-mm midline
      trough in the vertebrae and intervening disc spaces from C-2 to T-3. Rapid and
      successful decompression of the entire ventral cervical and upper thoracic
      epidural space was achieved using this technique. Understanding that the surgical
      treatment of discitis or osteomyelitis can often result in a kyphotic deformity
      or frank instability, the patient was immobilized in a cervical collar following
      surgery and underwent vigilant monitoring with serial plain radiographs, CT
      scans, and MR images. These neuroimaging studies confirmed complete resolution of
      the abscess and the slow development of a mild, stable kyphotic deformity. At the
      1-year follow-up, the patient was ambulating and had returned to work. A trough
      corpectomy is a viable surgical approach that allows for rapid decompression of
      ventral cervical and upper thoracic epidural abscesses while obviating the need
      for same-setting fusion and fixation.

PMID- 20672960
TI  - The biomechanical contribution of varying posterior constructs following anterior
      thoracolumbar corpectomy and reconstruction.
AB  - OBJECT: Thoracolumbar corpectomy is a procedure commonly required for the
      treatment of various pathologies involving the vertebral body. Although the
      biomechanical stability of anterior reconstruction with plating has been studied,
      the biomechanical contribution of posterior instrumentation to anterior
      constructs remains unknown. The purpose of this study was to evaluate
      biomechanical stability after anterior thoracolumbar corpectomy and
      reconstruction with varying posterior constructs by measuring bending stiffness
      for the axes of flexion/extension, lateral bending, and axial rotation. METHODS:
      Seven fresh human cadaveric thoracolumbar spine specimens were tested intact and
      after L-1 corpectomy and strut grafting with 4 different fixation techniques:
      anterior plating with bilateral, ipsilateral, contralateral, or no posterior
      pedicle screw fixation. Bending stiffness was measured under pure moments of +/-
      5 Nm in flexion/extension, lateral bending, and axial rotation, while maintaining
      an axial preload of 100 N with a follower load. Results for each configuration
      were normalized to the intact condition and were compared using ANOVA. RESULTS:
      Spinal constructs with anterior-posterior spinal reconstruction and bilateral
      posterior pedicle screws were significantly stiffer in flexion/extension than
      intact spines or spines with anterior plating alone. Anterior plating without
      pedicle screw fixation was no different from the intact spine in
      flexion/extension and lateral bending. All constructs had reduced stiffness in
      axial rotation compared with intact spines. CONCLUSIONS: The addition of
      bilateral posterior instrumentation provided significantly greater stability at
      the thoracolumbar junction after total corpectomy than anterior plating and
      should be considered in cases in which anterior column reconstruction alone may
      be insufficient. In cases precluding bilateral posterior fixation, unilateral
      posterior instrumentation may provide some additional stability.

PMID- 20672961
TI  - Upper thoracic spine arthroplasty via the anterior approach.
AB  - Significant progress has been made in lumbar and cervical disc replacement
      therapy. Several cervical disc prostheses have recently gained FDA approval.
      Although arthroplasty has not been previously described in the thoracic spine,
      selected patients with long-segment fusion to the level of C-7 have altered
      cervicothoracic and upper thoracic biomechanics and may benefit from motion
      preservation therapy for T1-2 disc herniation. Currently, FDA-approved prostheses
      are indicated only for patients with single-level degenerative disc disease
      between C-3 and C-7 and no history of cervical arthrodesis. The authors describe
      a 52-year-old woman who had previously undergone C3-7 fusion and returned 4 years
      later with symptoms of C-8 myeloradiculopathy and radiological evidence of T1-2
      degenerative disc disease. She underwent T1-2 arthroplasty in which a Prestige
      artificial cervical disc was placed via an anterior cervicothoracic approach.
      Motion at C7-T1 and T1-2 was preserved, and the patient made an excellent
      clinical recovery.

PMID- 20672962
TI  - Ball tip technique for thoracic pedicle screw placement in patients with
      adolescent idiopathic scoliosis.
AB  - OBJECT: The aim in this study was to evaluate the efficacy of the ball tip
      technique in placing thoracic pedicle screws (TPSs), as compared with the
      conventional freehand technique, in both a cadaveric study and a clinical study
      of patients with adolescent idiopathic scoliosis. Although posterior spinal
      surgery using TPSs has been widely applied, these screws are associated with the
      potential risk of vascular, pulmonary, or neurological complications. To further
      enhance the accuracy and safety of TPS placement, the authors developed the ball
      tip technique. METHODS: After creating an appropriate starting point for probe
      insertion, a specially designed ball tip probe consisting of a ball-shaped tip
      with a flexible metal shaft is used to make a guide hole into the pedicle.
      Holding the probe with the fingertips while using an appropriate amount of
      pressure or by tapping it gently and continuously with a hammer, one can safely
      insert the ball tip probe into the cancellous channel in the pedicle. In a
      cadaveric study, 5 spine fellows with similar levels of experience in placing
      TPSs applied the ball tip or the conventional technique to place screws in 5
      cadavers with no spinal deformities. The incidence of misplaced screws was
      evaluated by dissecting the spines. In a clinical study, 40 patients with
      adolescent idiopathic scoliosis underwent posterior surgery with TPS placement
      via the ball tip or conventional technique (20 patients in each treatment group).
      The accuracy of the TPS placements was evaluated on postoperative axial CT
      scanning. RESULTS: In the cadaveric study, 100 TPSs were evaluated, and the
      incidence of misplaced screws was 14% in the ball tip group and 34% in the
      conventional group (p = 0.0192). In the clinical study, 574 TPSs were evaluated.
      One hundred seventy-one intrapedicular screws (67%) were recognized in the
      conventional group and 288 (90%) in the ball tip group (p < 0.01). In the
      conventional and ball tip groups, the respective numbers of TPSs with a pedicle
      breach of < or = 2 mm were 20 (8%) and 15 (5%), those with a pedicle breach of >
      2 mm were 32 (13%) and 9 (3%; p < 0.01), and those located in the costovertebral
      joints were 32 (13%) and 7 (2%). CONCLUSIONS: In both cadaveric and clinical
      studies the ball tip technique enhanced the accuracy of TPS placement as compared
      with the conventional freehand technique. Thus, the ball tip technique is useful
      for the accurate and safe placement of TPSs in deformed spines.

PMID- 20672963
TI  - Biomechanical evaluation of posterior thoracic transpedicular discectomy.
AB  - OBJECT: The authors investigated the biomechanical properties of transpedicular
      discectomy in the thoracic spine and compared the effects on spinal stability of
      a partial and total facetectomy. METHODS: Human thoracic specimens were tested
      while intact, after a transpedicular discectomy with partial facetectomy, and
      after an additional total facetectomy was incorporated. Nonconstraining pure
      moments were applied under load control (maximum 7.5 Nm) to induce flexion,
      extension, lateral bending, and axial rotation while spinal motion was measured
      at T8-9 optoelectronically. The range of motion (ROM) and lax zone were
      determined in each specimen and compared among conditions. RESULTS:
      Transpedicular discectomy with and without a total facetectomy significantly
      increased the ROM and lax zone in all directions of loading compared with the
      intact spine (p < 0.008). The segmental increase in ROM observed with the
      transpedicular discectomy was 25%. The additional total facetectomy created an
      insignificant 3% further increase in ROM compared with medial facetectomy (p >
      0.2). CONCLUSIONS: Transpedicular discectomy can be performed in the thoracic
      spine with a modest decrease in stability expected. Because the biomechanical
      behavior of a total facetectomy is equivalent to that of a medial facetectomy,
      the additional facet removal may be incorporated without further biomechanical
      consequences.

PMID- 20672964
TI  - Defining the safe working zones using the minimally invasive lateral
      retroperitoneal transpsoas approach: an anatomical study.
AB  - OBJECT: The lateral retroperitoneal transpsoas approach is being increasingly
      employed to treat various spinal disorders. The minimally invasive blunt
      retroperitoneal and transpsoas dissection poses a risk of injury to major nervous
      structures. The addition of electrophysiological monitoring potentially decreases
      the risk of injury to the lumbar plexus. With respect to the use of the direct
      transpsoas approach, however, there is sparse knowledge regarding the
      relationship between the retroperitoneum/psoas muscle and the lumbar plexus at
      each lumbar segment. The authors undertook this anatomical cadaveric dissection
      study to define the anatomical safe zones relative to the disc spaces for
      prevention of nerve injuries during the lateral retroperitoneal transpsoas
      approach. METHODS: Twenty lumbar segments were dissected and studied. The
      relationship between the retroperitoneum, psoas muscle, and the lumbar plexus was
      analyzed. The area between the anterior and posterior edges of the vertebral body
      (VB) was divided into 4 equal zones. Radiopaque markers were placed in each disc
      space at the midpoint of Zone III (middle posterior quarter). At each segment,
      the psoas muscle, lumbar plexus, and nerve roots were dissected. The distribution
      of the lumbar plexus with reference to the markers at each lumbar segment was
      analyzed. RESULTS: All parts of the lumbar plexus, including nerve roots, were
      found within the substance of the psoas muscle dorsal to the posterior fourth of
      the VB (Zone IV). No Zone III marker was posterior to any part of the lumbar
      plexus with the exception of the genitofemoral nerve. The genitofemoral nerve
      travels obliquely in the substance of the psoas muscle from its origin to its
      innervations. It emerges superficially and anterior from the medial border of the
      psoas at the L3-4 level and courses along the anterior medial fourth of the L-4
      and L-5 VBs (Zone I). The nerves of the plexus that originate at the upper lumbar
      segments emerge from the lateral border of the psoas major and cross obliquely
      into the retroperitoneum in front of the quadratus lumborum and the iliacus
      muscles to the iliac crest. CONCLUSIONS: With respect to prevention of direct
      nerve injury, the safe anatomical zones at the disc spaces from L1-2 to L3-4 are
      at the middle posterior quarter of the VB (midpoint of Zone III) and the safe
      anatomical zone at the L4-5 disc space is at the midpoint of the VB (Zone II-Zone
      III demarcation). There is risk of direct injury to the genitofemoral nerve in
      Zone II at the L2-3 space and in Zone I at the lower lumbar levels L3-4 and L4-5.
      There is also a potential risk of injury to the ilioinguinal, iliohypogastric,
      and lateral femoral cutaneous nerves in the retroperitoneal space where they
      travel obliquely, inferiorly, and anteriorly to the reach the iliac crest and the
      abdominal wall.

PMID- 20672965
TI  - Symptomatic relevance of intravertebral cleft in patients with osteoporotic
      vertebral fracture.
AB  - OBJECT: The present study was designed to determine clinical and radiographic
      characteristics of unhealed osteoporotic vertebral fractures (OVFs) and the role
      of fracture mobility and an intravertebral cleft in the regulation of pain
      symptoms in patients with an OVF. METHODS: Patients who had persistent low-back
      pain for 3 months or longer and a collapsed thoracic or lumbar vertebra that had
      an intervertebral cleft and abnormal mobility were referred to as having unhealed
      OVFs. Twenty-four patients with an unhealed OVF and 30 patients with an acute OVF
      were compared with regard to several clinical and radiographic features including
      the presence of an intravertebral fluid sign. Subsequently, the extent of dynamic
      mobility of the fractured vertebra was analyzed for correlation with the
      patients' age, duration of symptoms, back pain visual analog scale (VAS) score,
      and performance status. Finally, in cases of unhealed OVFs, the subgroup of
      patients with positive fluid signs was compared with the subgroup of patients
      with negative fluid signs. RESULTS: Patients with an unhealed OVF were more
      likely to have a crush-type fracture, shorter vertebral height of the fractured
      vertebra, and a fracture with a positive fluid sign than those with an acute OVF.
      The extent of dynamic mobility of the vertebra correlated significantly with the
      VAS score in patients with an unhealed OVF. In addition, a significant
      correlation with the extent of dynamic vertebral mobility with performance status
      was seen in patients with an unhealed OVF and those with an acute OVF. Of the 24
      patients with an unhealed OVF, 14 had a positive fluid sign in the affected
      vertebra. Patients with a positive fluid sign exhibited a statistically
      significantly greater extent of dynamic vertebral mobility, a higher VAS score, a
      higher performance status grade, and a greater likelihood of having a crush-type
      fracture than those with a negative fluid sign. All but 1 patient with an
      unhealed OVF and a positive fluid sign had an Eastern Cooperative Oncology Group
      Performance Status Grade 3 or 4 (bedridden most or all of the time). In sharp
      contrast, all 10 patients with an unhealed OVF and a negative fluid sign were
      Grade 1 or 2. CONCLUSIONS: Unhealed OVFs form a group of fractures that are
      distinct from acute OVFs regarding radiographic morphometry and contents of the
      intravertebral cleft. Dynamic vertebral mobility serves as a primal pain
      determinant in patients with an unhealed OVF and potentially in those with an
      acute OVF. Fluid accumulation in the intravertebral cleft of unhealed OVFs likely
      reflects long-term bedridden positioning of the patients in daily activity.

PMID- 20672966
TI  - Clinical application of a novel assessment for lumbosacral stability.
AB  - OBJECT: To evaluate the grade of lumbosacral stability, shape analysis was
      conducted on plain radiographs of the lumbar spine. METHODS: One hundred twenty
      six patients were classified into 2 groups: those with a single-segment disc
      space narrowing at L5-S1 or at L4-5. Stability was evaluated using the
      discriminant function (z score) derived from the analysis of radiographic
      parameters-that is, relative thickness of transverse process of L-5 and the
      sacral table angle. RESULTS: In patients with a space narrowing at L5-S1, the
      author observed a significantly slender L-5 transverse process and acute
      obliquity of the sacral endplate; accordingly, the z score was negative. In
      patients with a broad transverse process and a positive z score, the segment
      associated with disc height loss was L4-5. Thus, a close correlation was found
      between the site of the disc height loss and the bony characteristics of L-5 and
      S-1. Furthermore, it could be expected with a high degree reliability that when
      young adult patients had a z score less than -2 or -3, their L-5 vertebra would
      develop degenerative spondylolisthesis after middle age and the L5-S1 segment
      could be saved from age-related alterations as long as the z score was greater
      than 2.5. The constitutional characteristics of the lumbosacral junction may
      exert a major influence on the site of disc degeneration. CONCLUSIONS: Stability
      at the lumbosacral junction was thought to be quantitatively represented by the z
      score, with z being designated the lumbosacral stability score.

PMID- 20672967
TI  - Adult cervical intramedullary teratoma: first reported immature case.
AB  - Intramedullary teratomas, particularly adult cervicothoracic lesions, are
      extremely rare. Up to now only 6 cases of intramedullary cervical teratomas have
      been reported in adults, and all of these were histologically mature. The authors
      present the case of a 35-year-old man with progressive myelopathic symptoms who
      was admitted through an outpatient clinic and was surgically treated. The
      characteristics, diagnosis, epidemiology, and treatment of cervical
      intramedullary teratomas in adults are also reviewed. Postoperative MR imaging
      showed that the tumor had been near totally removed, and severely adherent tissue
      remained ventrocranially with tiny focal enhancement on follow-up MR imaging.
      Pathological examinations revealed immature teratoma without any malignant
      component. Adjuvant therapy was not performed. Although no change in neurological
      findings and symptoms was apparent postoperatively, lesion regrowth was
      demonstrated on MR imaging 4 months after surgery. At 8 months postoperatively,
      myelopathic symptoms had developed and a huge intramedullary tumor recurred
      according to MR imaging. This case is the seventh reported instance of
      intramedullary cervical teratoma in an adult, and the first case report of the
      immature type with malignant features.

PMID- 20672968
TI  - Sacral fractures following stand-alone L5-S1 anterior lumbar interbody fusion for
      isthmic spondylolisthesis.
AB  - Recent studies have demonstrated excellent results in treating isthmic
      spondylolisthesis via an anterior lumbar interbody fusion (ALIF). The authors
      describe 3 patients with isthmic spondylolisthesis at L5-S1 who experienced
      sacral fractures after insertion of a unique, stand-alone anterior interbody
      fixation device. Three consecutive patients at a single institution were treated
      for Grade I spondylolisthesis at L5-S1 via a standalone ALIF with insertion of a
      novel biomechanical interbody device. This device is made of polyetheretherketone
      and has an integrated system for internal fixation into the vertebral bodies. In
      each patient a bone morphogenetic protein-soaked sponge was placed for the
      fusion. The indications for treatment in each patient were back and radicular
      pain that had been unsuccessfully treated with conservative measures. All 3
      patients had reduction of their spondylolisthesis and resolution of their
      unilateral radiculopathies immediately postoperatively. Within 1 month of
      surgery, all 3 patients had failure of the device and recurrence of their
      symptoms. In each case the failure was due to fracture of the anterior portion of
      the S-1 body. Each patient underwent reduction and pedicle screw fixation at L5
      S1. In all cases, there was successful reduction in their recurrent
      spondylolisthesis and resolution of their radiculopathies. Treatment of Grade I
      isthmic spondylolisthesis at L5-S1 with stand-alone ALIF and fixation can lead to
      sacral fracture from high stress loads at that level in the spine, and
      consideration should be made either for supplemental pedicle screw fixation or a
      completely posterior approach.

PMID- 20672969
TI  - Re: The use of flexion-extension magnetic resonance imaging for evaluating signal
      intensity changes of the cervical spinal cord.

PMID- 20672970
TI  - Granulocyte macrophage colony-stimulating factor is required for cytokine
      induction by a highly 6-branched 1,3-beta-D-glucan from Aureobasidium pullulans
      in mouse-derived splenocytes.
AB  - We have previously obtained and elucidated the precise structure of a highly
      branched 1,3-beta-D-glucan (with 6-monoglucopyranosyl side chains), Aureobasidium
      pullulans-fermented beta-D-glucan (AP-FBG), from the fungus A. pullulans.
      However, the mechanism(s) of the effects of AP-FBG on in vitro mouse primary
      cells have not been analyzed in detail. Herein, we report that the induction of
      cytokines by AP-FBG was dependent on the existence of a granulocyte macrophage
      colony-stimulating factor (GM-CSF); this is similar way to be a typical 1,3-beta
      D-glucan from Sparassis crispa (SCG), which is a 1,3-beta-D-glucopyranosyl
      backbone with single 1,6-beta-D-glucopyranosyl side branching units every three
      residues. In other words, the production of cytokines in DBA/2-mouse-derived
      splenocytes by AP-FBG was completely hampered by an anti-GM-CSF neutralizing
      monoclonal antibody. Furthermore, the addition of exogenous GM-CSF to C57BL/6
      derived splenocytes, which are less sensitive to AP-FBG, induced the production
      of cytokines by AP-FBG. Therefore, GM-CSF is indispensable for the induction of
      cytokines by AP-FBG in mouse-derived splenocytes. This finding has provided a new
      insight into our understanding of the actions of beta-D-glucan but will also aid
      in the design and development of more effective beta-D-glucan agents.

PMID- 20672971
TI  - A qualitative study of the barriers and facilitators to retention-in-care among
      HIV-positive women in the rural southeastern United States: implications for
      targeted interventions.
AB  - Retention in HIV medical care has been recognized as critical for long-term
      favorable clinical outcomes among HIV-positive patients. However, relatively
      little is known about specific factors related to HIV medical care adherence
      among HIV-positive women in rural areas in the United States, where the epidemic
      is rapidly growing among minorities and women. The objective of the current study
      was to assess barriers and facilitators to HIV clinic visit adherence among HIV
      positive women in the rural southeastern region of the United States. Forty HIV
      positive women were recruited from four outpatient clinics providing services to
      HIV-positive patients residing in 23 predominately rural counties in Alabama.
      Four focus groups were conducted ranging from 5 to 16 participants each. Content
      analysis was used to analyze and interpret the data. Data coding and sorting was
      conducted using QRS NVivo 8 software. Participants were predominately African
      American (92.3%) ranging in age from 29 to 69 years (mean = 46.1 years). On
      average, participants reported living with HIV for 8.8 years. Factors that
      impacted participants' ability to maintain clinic visit appointments included
      personal, contextual, and community/environmental factors that included:
      patient/provider relationships, family support, access to transportation,
      organizational infrastructure of the health care facility visited and perceived
      HIV stigma within their communities. The current study highlights the myriad of
      retention-in-care barriers faced by HIV-positive women living in rural areas in
      the southeastern United States. Innovative multilevel interventions that address
      these factors are sorely needed to increase long-term retention-in-care among HIV
      positive women residing in rural areas.

PMID- 20672972
TI  - Toward universal access to HIV counseling and testing and antiretroviral
      treatment in Ethiopia: looking beyond HIV testing and ART initiation.
AB  - Expanding access to HIV counseling and testing (HCT) and antiretroviral treatment
      (ART) has reduced morbidity and mortality in people living with HIV/AIDS. As a
      result, many countries are scaling up HIV/AIDS services. In this paper we discuss
      challenges experienced during the move toward universal access to HCT and ART
      services in Ethiopia. We reviewed routine reports from the Ministry of Health and
      implementing partners. We also had interviews, about linkage to and retention in
      care of patients, with 10 HIV/AIDS program managers, as well as 2 to 7 health
      care providers and 5 to 15 patients in each of 23 health centers and 32 hospitals
      in all regions of the country. We found that the number of people tested for HIV
      increased 10-fold from 435,854 in 2005 to 4,559,954 in 2008. Only 61% of the HIV
      positive patients were linked to chronic care immediately after tested for HIV.
      The number of patients initiated on ART annually increased from 26,021 in 2005 to
      53,696 in 2008. Attrition of patients increased from 18% in 2005 to 26% in 2008.
      Our interviews indicated that fear of stigma, transport cost, feeling healthy and
      opting for traditional medicines were the main reasons for poor linkage to and
      retention in care. Lack of nutrition and feeling better were also reasons for
      poor retention. In conclusion, in spite of the rapid scale-up of HCT and ART
      services in Ethiopia, linkage and retention were not adequate. Therefore,
      strategies should be developed and implemented to improve linkage and retention.

PMID- 20672973
TI  - Short communication: Lack of immune response in rapid progressor morphine
      dependent and SIV/SHIV-infected rhesus macaques is correlated with downregulation
      of TH1 cytokines.
AB  - Our previous studies have shown two distinct disease patterns (rapid and normal
      onset of clinical symptoms) in morphine-dependent SHIV/SIV-inoculated rhesus
      macaques. We have also shown that control as well as 50% of morphine-dependent
      macaques (normal progressor) developed humoral and cellular immune responses
      whereas the other half of the morphine-dependent macaques (rapid progressor) did
      not develop antiviral immune responses after infection with SIV/SHIV. In the
      present study, we analyzed the association between cytokine production, immune
      response, and disease progression. To study the immunological effects of morphine
      at cytokine levels in the context of a lentiviral infection, we inoculated rhesus
      macaques with a mixture of SHIV(KU-18), SHIV(89.6)P, and SIV/17E-Fr. These
      animals were followed for a period of 56 weeks for cytokine level production in
      plasma. Drug-dependent rapid disease progressors exhibited an increase in IL-18
      and IL-1Ra and a decrease in IL-12 levels in the plasma. Morphine-dependent
      normal progressors and control macaques exhibited an increase in both IL-18 and
      IL-12, whereas IL-Ra levels remained constant throughout the observation period.
      These results suggest that rapid disease progression in relation to morphine
      dependency may be the result of an altered cytokine profile.

PMID- 20672976
TI  - Distribution of the Iberian Calopteryx damselflies and its relation with
      bioclimatic belts: evolutionary and biogeographic implications.
AB  - Using bioclimatic belts as habitat and distribution predictors, the present study
      examines the implications of the potential distributions of the three Iberian
      damselflies, Calopteryx Leach (Odonata: Calopterygidae), with the aim of
      investigating the possible consequences in specific interactions among the
      species from a sexual selection perspective and of discussing biogeographical
      patterns. To obtain the known distributions, the literature on this genus was
      reviewed, relating the resulting distributions to bioclimatic belts. Specific
      patterns related to bioclimatic belts were clearly observed in the Mediterranean
      region. The potential distribution maps and relative frequencies might involve
      latitudinal differences in relative abundances, C. virgo meridionalis Selys being
      the most abundant species in the Eurosiberian region, C. xanthostoma
      (Charpentier) in the northern half of the Mediterranean region and C.
      haemorrhoidalis (Vander Linden) in the rest of this region. These differences
      might explain some previously described latitudinal differences in secondary
      sexual traits in the three species. Changes in relative abundances may modulate
      interactions among these species in terms of sexual selection and may produce
      sexual character displacement in this genus. C. virgo meridionalis distribution
      and ecological requirements explain its paleobiogeography as a species which took
      refuge in Iberia during the Wurm glaciation. Finally, possible consequences in
      species distributions and interactions are discussed within a global climate
      change context.

PMID- 20672974
TI  - Short communication: Nucleotide variation and positively selected sites in HIV
      type 1 reverse transcriptase among heterosexual transmission pairs.
AB  - Mutations in the env gene of HIV-1 have been the primary focus in most
      epidemiologically related cohort studies of virus evolution and very limited
      studies have focused on the reverse transcriptase (RT) region, the primary target
      of antiretroviral therapy (ART). Hence, we measured the selection pressure and
      searched for the positively selected sites in the RT sequences amplified from HIV
      1-infected heterosexual transmission pairs. Married couples (n = 10) who were ART
      naive were included in this study. Phylogenetic analysis, the measurement of
      synonymous and nonsynonymous ratio (dN/dS) and the interpatient nucleotide
      variation, was done. Phylogenetic analysis demonstrated distinct subclusters of
      the RT sequences from heterosexual transmission pairs and the median (IQR)
      nucleotide variation between the epidemiologically related transmission pairs was
      significantly (p < 0.001) lower [0.01% (0.01-0.02%)] compared to the
      epidemiologically unrelated transmission pairs [0.04% (0.03-0.04%)]. The ratio of
      dN/dS was <1 and codons 135, 162, 166, 207, and 211 were positively selected in
      >50% of the donor and recipient RT sequences. Purifying selection pressure and
      low nucleotide variation in the RT sequences between epidemiologically related
      transmission pairs highlight its essential role in HIV-1 replication. The effect
      of the RT positively selected mutations that persist over time following
      transmission between individuals needs to be studied to determine the fitness
      cost of the mutations in vivo, which may possibly represent good targets for
      inclusion in HIV-1 vaccines.

PMID- 20672977
TI  - Fungi associated with the hemlock woolly adelgid, Adelges tsugae, and assessment
      of entomopathogenic isolates for management.
AB  - Fungi associated with the hemlock wooly adelgid, Adelges tsugae Annand
      (Hemiptera: Adelgidae), were collected throughout the eastern USA and southern
      China. Twenty fungal genera were identified, as were 79 entomopathogenic
      isolates, including: Lecanicillium lecanii (Zimmermann) (Hypocreales: Insertae
      sedis), Isaria farinosa (Holm: Fries.) (Cordycipitaceae), Beauveria bassiana
      (Balasamo) (Hyphomycetes), and Fusarium spp (Nectriaceae). The remaining fungal
      genera associated with insect cadavers were similar for both the USA and China
      collections, although the abundance of Acremonium (Hypocreaceae) was greater in
      China. The entomopathogenic isolates were assayed for efficacy against Myzus
      persicae (Sulzer) (Homoptera: Aphididae) and yielded mortality ranging from 3 to
      92%. Ten isolates demonstrating the highest efficacy were further assessed for
      efficacy against field-collected A. tsugae under laboratory conditions. Overall,
      two B. bassiana, one L. lecanii, and a strain of Metarhizium anisopliae
      (Metchnikoff) (Hypocreales: Clavicipitaceae), demonstrated significantly higher
      efficacy against A. tsugae than the others. Isolates were further evaluated for
      conidial production, germination rate and colony growth at four temperatures
      representative of field conditions. All isolates were determined to be mesophiles
      with optimal temperature between 25-30 degrees C. In general, conidial production
      increased with temperature, though two I. farinosa produced significantly more
      conidia at cooler temperatures. When efficacy values were compared with conidial
      production and temperature tolerances, Agricultural Research Service Collection
      of Entomopathogenic Fungi (ARSEF) 1080, 5170, and 5798 had characteristics
      comparable to the industrial B. bassiana strain GHA.

PMID- 20672978
TI  - Distribution of alpha(IV) collagen chains in the ocular anterior segments of
      adult mice.
AB  - The distribution of the collagen chains from alpha1(IV) to alpha6(IV) could serve
      as a basis for the characterization of type IV collagen. In this study,
      immunohistochemistry of the ocular anterior segment of adult mice was performed
      using specific monoclonal antibodies against each chain in the series from
      alpha1(IV) to alpha6(IV). The results show that the components of type IV
      collagen in vascular basement membranes are alpha1(IV) and alpha2(IV) with or
      without alpha5(IV) and alpha6(IV) chains and those in epithelium and muscle
      basement membranes are alpha1(IV), alpha2(IV), alpha5(IV), and alpha6(IV) chains.
      In corneal endothelium, pigmented epithelium of iris and ciliary body, and
      trabecular meshwork, alpha3(IV) and alpha4(IV) chains are also expressed in
      addition to alpha1(IV), alpha2(IV), alpha5(IV), and alpha6(IV) chains. Moreover,
      we investigated the change in molecular composition in ciliary body during
      postnatal development. alpha3(IV) and alpha4(IV) chains were also expressed in
      addition to alpha1(IV), alpha2(IV), alpha5(IV), and alpha6(IV) chains in ciliary
      pigmented epithelium basement membrane from 7 days after birth. This result
      suggests that the basement membranes gradually change their biochemical features
      owing to temporal regulation. Taken together, these findings suggest that the
      different distribution and the developmental expression of alpha1(IV) to
      alpha6(IV) chains are associated with the tissue-specific function of type IV
      collagen in basement membranes.

PMID- 20672979
TI  - Efficacy of tree trunk coating materials in the control of the apple clearwing,
      Synanthedon myopaeformis.
AB  - The efficacy of trunk treatment with three materials, cotton seed oil, lime and
      used motor oil, were evaluated for the control of apple clearwing, Synanthedon
      myopaeformis (Borkhausen) (Lepidoptera: Sesiidae) in an apple orchard during two
      successive years (2004 and 2005). The weekly total number of adult catches and
      exuviae was recorded each year. No treatments caused significant reductions in
      mean numbers of adults caught in bait traps or the exuviae protruding from the
      barks of tree trunks and thick branches in the first year of the study whereas
      all of them differed significantly from each other or from water-treated control
      in the second year (P < 0.05). A comparison of the mean numbers of adult catches
      and exuviae in both years revealed significant differences between the used motor
      oil and cotton seed oil treatments (P < 0.05). The lime treatments in both years
      significantly differed in terms of adult catches, but not exuviae (P<0.05). In
      the second year, compared with those in water-treated control plots, the mean
      number of adult catches and exuviae decreased by 81.3% and 88.3% in the used
      motor oil-treated plots, and by 70.8% and 83.3% in the cotton seed oil-treated
      plots, respectively. Although population reductions in the lime treatment were
      significant in the second year, the effect was at a much reduced level in
      comparison to the two oil treatments. The overall results suggest that used motor
      oil and cotton seed oil may have potential for the control of apple clearwing.

PMID- 20672980
TI  - The nest architecture of the ant Odontomachus brunneus.
AB  - The architecture of the subterranean nests of the ant Odontomachus brunneus
      (Patton) (Hymenoptera: Formicidae) was studied by means of casts with dental
      plaster or molten metal. The entombed ants were later recovered by dissolution of
      plaster casts in hot running water. O. brunneus excavates simple nests, each
      consisting of a single, vertical shaft connecting more or less horizontal, simple
      chambers. Nests contained between 11 and 177 workers, from 2 to 17 chambers, and
      28 to 340 cm(2) of chamber floor space and reached a maximum depth of 18 to 184
      cm. All components of nest size increased simultaneously during nest enlargement,
      number of chambers, mean chamber size, and nest depth, making the nest shape
      (proportions) relatively size-independent. Regardless of nest size, all nests had
      approximately 2 cm(2) of chamber floor space per worker. Chambers were closer
      together near the top and the bottom of the nest than in the middle, and total
      chamber area was greater near the bottom. Colonies occasionally incorporated
      cavities made by other animals into their nests.

PMID- 20672981
TI  - Delay of cell cycle progression and induction death of cancer cells on type I
      collagen fibrils [corrected].
AB  - Here, we report the behavior of three kinds of human cancer cell lines (Caco-2,
      MCF-7, HT-1080) on type I collagen substrates, which are in two-dimensional
      coated collagen or three-dimensional fibrils form. All tested cells on coated
      collagen adhered and proliferated. However, in the case of collagen fibrils, the
      proliferation of cancer cells was suppressed. Furthermore, Akt activation, which
      is known as a cell-survival signal, was inhibited in cells on collagen fibrils.
      But the activation of ERK1/2 was not completely inhibited. In Caco-2 cells, delay
      of cell cycle progression and cell death occurred at the same time. Thus, cell
      division and cell death occurred at equivalent rates on the collagen fibrils, and
      cell growth seemed to be stopped. These results imply that the fibril form of
      collagen plays a potential role in inhibiting the growth of cancer cells.

PMID- 20672982
TI  - The foraging tunnel system of the Namibian desert termite, Baucaliotermes
      hainesi.
AB  - The harvester termite, Baucaliotermes hainesi (Fuller) (Termitidae:
      Nasutitermitinae), is an endemic in southern Namibia, where it collects and eats
      dry grass. At the eastern, landward edge of the Namib Desert, the nests of these
      termites are sometimes visible above ground surface, and extend at least 60 cm
      below ground. The termites gain access to foraging areas through underground
      foraging tunnels that emanate from the nest. The looseness of the desert sand,
      combined with the hardness of the cemented sand tunnels allowed the use of a
      gasoline-powered blower and soft brushes to expose tunnels lying 5 to 15 cm below
      the surface. The tunnels form a complex system that radiates at least 10 to 15 m
      from the nest with cross-connections between major tunnels. At 50 to 75 cm
      intervals, the tunnels are connected to the surface by vertical risers that can
      be opened to gain foraging access to the surrounding area. Foraging termites
      rarely need to travel more than a meter on the ground surface. The tunnels swoop
      up and down forming high points at riser locations, and they have a complex
      architecture. In the center runs a smooth, raised walkway along which termites
      travel, and along the sides lie pockets that act as depots where foragers deposit
      grass pieces harvested from the surface. Presumably, these pieces are transported
      to the nest by a second group of termites. There are also several structures that
      seem to act as vertical highways to greater depths, possibly even to moist soil.
      A census of a single nest revealed about 45,000 termites, of which 71% were
      workers, 9% soldiers and 6% neotenic supplementary reproductives. The nest
      consisted of a hard outer "carapace" of cemented sand, with a central living
      space of smooth, sweeping arches and surfaces. A second species of termite,
      Promirotermes sp. nested in the outer carapace.

PMID- 20672983
TI  - Microarray analysis of juvenile hormone response in Drosophila melanogaster S2
      cells.
AB  - A microchip array encompassing probes for 14,010 genes of Drosophila melanogaster
      was used to analyze the effect of juvenile hormone (JH) on genome-wide gene
      expression. JH is a member of a group of insect hormones involved in regulating
      larval development and adult reproductive processes. Total RNA was isolated from
      Drosophila S2 cells after 4 hours treatment with 250 ng/ml (10R) JH III or 250
      ng/ml methyl linoleate. A collection of 32 known or putative genes demonstrated a
      significant change with JH III treatment (r > 2.0, P <or= 0.005). Of these, the
      abundance of 13 transcripts was significantly increased and 19 decreased. The
      expression of a subset of these loci was analyzed by real-time quantitative
      reverse transcription polymerase chain reaction (RT-qPCR). Three loci that
      exhibited constant expression in the presence and absence of JH III (RP49
      [FBgn0002626], FBgn0023529, and FBgn0034354) were evaluated and found to be
      reliable invariant reference transcripts for real-time RT-qPCR analysis using
      BestKeeper and geNorm software. Increased expression in presence of JH III was
      confirmed by real-time RTqPCR analysis. However, only one of five loci that
      exhibited reduced expression on microarrays could be confirmed as significantly
      reduced (P <or= 0.05). Among the confirmed JH III up-regulated genes were two
      loci of unknown function (FBgn0040887 and FBgn0037057) and Epac, an exchange
      protein directly activated by cyclic AMP, a guanine nucleotide exchange factor
      for Rap1 small GTPase.

PMID- 20672984
TI  - Electrospun chitosan-alginate nanofibers with in situ polyelectrolyte
      complexation for use as tissue engineering scaffolds.
AB  - Electrospun natural biopolymers are of great interest in the field of
      regenerative medicine due to their unique structure, biocompatibility, and
      potential to support controlled release of bioactive agents and/or the growth of
      cells near a site of interest. The ability to electrospin chitosan and alginate
      to form polyionic complexed nanofibrous scaffolds was investigated. These
      nanofibers crosslink in situ during the electrospinning process, and thus do not
      require an additional chemical crosslinking step. Although poly(ethylene oxide)
      (PEO) is required for the electrospinning, it can be subsequently removed from
      the nanofibers simply by incubating in water for a few days, as confirmed by
      attenuated total reflectance Fourier transform infrared. Solutions that allowed
      uniform nanofiber formation were found to have viscosities in the range of 0.15
      0.7 Pa.s and conductivities below 4 mS/cm for chitosan-PEO and below 2.2 mS/cm
      for alginate-PEO. The resultant nanofibers both before and after PEO extraction
      were found to be uniform and on the order of 100 nm as determined by scanning
      electron microscopy. The dynamic rheological properties of the polymer mixtures
      during gelation indicated that the hydrogel mixtures with low storage moduli
      provided uniform nanofiber formation without beaded structures. Increased amounts
      of chitosan in the PEO-extracted chitosan-alginate nanofibers resulted in a lower
      swelling ratio. Additionally, these nanofibrous scaffolds exhibit increased cell
      adhesion and proliferation compared to those made of alginate alone, due to the
      presence of the chitosan, which promotes the adsorption of serum proteins. Thus,
      these nanofibrous scaffolds formed purely via ionic complexation without toxic
      crosslinking agents have great potential for guiding cell behavior in tissue
      regeneration applications.

PMID- 20672985
TI  - Caterpillars and host plant records for 59 species of Geometridae (Lepidoptera)
      from a montane rainforest in southern Ecuador.
AB  - During four months of field surveys at the Reserva Biologica San Francisco in the
      south Ecuadorian Andes, caterpillars of 59 Geometridae species were collected in
      a montane rainforest between 1800 and 2800m altitude and reared to adults. The
      resulting data on host plant affiliations of these species was collated. The
      preimaginal stages of 58 and adult stages of all 59 species are depicted in
      colour plates. Observations on morphology and behaviour are briefly described.
      Five species, documented for the first time in the study area by means of larval
      collections, had not been previously collected by intensive light-trap surveys.
      Together with published literature records, life-history data covers 8.6% of the
      1271 geometrid species observed so far in the study area. For 50 species these
      are the first records of their early stages, and for another 7 the data
      significantly extend known host plant ranges. Most larvae were collected on
      shrubs or trees, but more unusual host plant affiliations, such as ferns (6
      geometrid species) and lichens (3 geometrid species), were also recorded. Thirty
      four percent of the caterpillars were infested by wasp or tachinid parasitoids.

PMID- 20672986
TI  - Osteosarcoma in a Marfan patient with a novel premature termination codon in the
      FBN1 gene.
AB  - Osteosarcoma is a malignant neoplasm of mesenchymal origin that is presumed to
      arise from osteoblasts. Considered a rare tumor, approximately 1000 cases of
      osteosarcoma are diagnosed in the United States each year, and osteosarcoma of
      the foot is rarer still. Marfan syndrome (MFS) is a rare genetic disorder that
      affects 1 in 5000 individuals and is caused by mutations in the fibrillin 1
      (FBN1) gene. MFS phenotype affects several body systems, including soft
      connective tissue and bone. Here we report, for the first time, an individual
      with MFS that was treated for osteosarcoma. Surgically resected tissue was used
      to initiate an osteosarcoma cell line (PSU-OS-M) that exhibits attachment
      independent growth and loss of contact inhibition in vitro. Genomic DNA was
      isolated from the tumor cells, and primers that anneal to intronic regions were
      used to amplify and sequence all 65 coding exons of the FBN1 gene. A two base
      pair insertion that results in a novel premature termination codon (PTC) was
      found in exon 52. Protein from the normal allele is detectable in PSU-OS-M cell
      conditioned medium, but protein from the mutant allele was not detectable.
      Immunofluorescent microscopy demonstrates that PSU-OS-M cells can assemble
      fibrillin 1 microfibrils in culture, and fibronectin assembly is normal. As such,
      the PSU-OS-M cell line is to our knowledge the first oncogenically transformed
      cell line with a mutant fibrillin gene and may serve as a useful tool for
      studying molecular mechanisms of MFS and nonsense-mediated decay.

PMID- 20672987
TI  - Comparing therapeutic ultrasound with microamperage stimulation therapy for
      improving the strength of Achilles tendon repair.
AB  - In exploring the effects of therapeutic ultrasound (US) and microamperage
      stimulation (MAS) on the biomechanical performance of repairing Achilles tendon
      in rats, 35 Sprague-Dawley rats receiving surgically induced injury to their
      right medial Achilles tendon were studied. The rats were divided into four groups
      of low-dose US (group 1, n = 10), high-dose US (group 2, n = 11), MAS (group 3, n
      = 7), and control (group 4, n = 7). The treatment started on day 6 after injury.
      Groups 1 and 2 received 4 min of daily US treatment at 1.0 and 2.0 W/cm(2),
      respectively. Group 3 received 30 min of daily transcutaneous MAS treatment.
      Group 4 received 30 min of daily sham MAS treatment. On day 31, the Achilles
      tendons were mechanically tested. Data on the right side were normalized to the
      left side and analyzed with MANOVA with alpha = 0.05. Results of MANOVA was
      significant and post hoc tests revealed that the normalized strength of groups 1,
      2, and 3 were higher than that of group 4 (p = 0.003) but no significant
      difference was found among the treatment groups. The ANOVA result of the
      normalized load relaxation and stiffness was p = 0.06 and p = 0.07, respectively.
      These findings suggested that both low/high doses of US and MAS therapies could
      improve the strength of Achilles tendon but in view of its short treatment time,
      US is considered to be more efficient than MAS for improving the strength of the
      repairing tendons.

PMID- 20672988
TI  - Checklist of Iranian Encyrtids (Hymenoptera: Chalcidoidea) with descriptions of
      new species.
AB  - A list of Iranian Encyrtidae (Hymenoptera: Chalcidoidea) is given for the first
      time. It includes 93 species representing 32 genera. Host information from Iran
      and distributional data are also provided. Three genera and 7 species are first
      recorded from Iran. New host records are provided for three species. Two new
      species, Gyranusoidea iranica sp. n. and Microterys iranicus sp. n., are
      described and diagnostic characters are provided for them.

PMID- 20672989
TI  - Reconstructing seasonal range expansion of the tropical butterfly, Heliconius
      charithonia, into Texas using historical records.
AB  - While butterfly responses to climate change are well studied, detailed analyses
      of the seasonal dynamics of range expansion are few. Therefore, the seasonal
      range expansion of the butterfly Heliconius charithonia L. (Lepidoptera:
      Nymphalidae) was analyzed using a database of sightings and collection records
      dating from 1884 to 1992 from Texas. First and last sightings for each year were
      noted, and residency time calculated, for each collection locality. To test
      whether sighting dates were a consequence of distance from source (defined as the
      southernmost location of permanent residence), the distance between source and
      other locations was calculated. Additionally, consistent directional change over
      time of arrival dates was tested in a well-sampled area (San Antonio). Also,
      correlations between temperature, rainfall, and butterfly distribution were
      tested to determine whether butterfly sightings were influenced by climate. Both
      arrival date and residency interval were influenced by distance from source:
      butterflies arrived later and residency time was shorter at more distant
      locations. Butterfly occurrence was correlated with temperature but not rainfall.
      Residency time was also correlated with temperature but not rainfall. Since
      temperature follows a north-south gradient this may explain the inverse
      relationship between residency and distance from entry point. No long-term
      directional change in arrival dates was found in San Antonio. The biological
      meaning of these findings is discussed suggesting that naturalist notes can be a
      useful tool in reconstructing spatial dynamics.

PMID- 20672990
TI  - A new species of Charassothrips Hood from Colombia (Insecta, Thysanoptera,
      Thripidae) with an updated key to the known species.
AB  - Charassothrips macroseta sp.n. is described and illustrated from Colombia. A key
      is provided to the five species now recognised in the Neotropical genus
      Charassothrips, each of which has the head and pronotum, mesonotum and metanotum
      prominently sculptured and the abdominal tergites with a craspedum on the
      posterior margins.

PMID- 20672991
TI  - Effects of allogeneic hematopoietic stem cell transplantation plus thymus
      transplantation on malignant tumors: comparison between fetal, newborn, and adult
      mice.
AB  - We have recently shown that allogeneic intrabone marrow-bone marrow
      transplantation + adult thymus transplantation (TT) is effective for hosts with
      malignant tumors. However, since thymic and hematopoietic cell functions differ
      with age, the most effective age for such intervention needed to be determined.
      We performed hematopoietic stem cell transplantation (HSCT) using the intrabone
      marrow method with or without TT from fetal, newborn, and adult B6 mice (H-2(b))
      into BALB/c mice (H-2(d)) bearing Meth-A sarcoma (H-2(d)). The mice treated with
      all types of HSCT + TT showed more pronounced regression and longer survival than
      those treated with HSCT alone in all age groups. Those treated with HSCT + TT
      showed increased numbers of CD4(+) and CD8(+) T cells but decreased numbers of Gr
      1/Mac-1 myeloid suppressor cells and decreased percentages of FoxP3 cells in
      CD4(+) T cells, compared with those treated with HSCT alone. In all mice, those
      treated with fetal liver cell (as fetal HSCs) transplantation + fetal TT or with
      newborn liver cell (as newborn HSCs) transplantation (NLT) + newborn TT (NTT)
      showed the most regression, and the latter showed the longest survival. The
      number of Gr-1/Mac-1 cells was the lowest, whereas the percentage of CD62L(
      )CD44(+) effector memory T cells and the production of interferon gamma (IFN
      gamma) were highest in the mice treated with NLT + NTT. These findings indicate
      that, at any age, HSCT + TT is more effective against cancer than HSCT alone and
      that NLT + NTT is most effective.

PMID- 20672992
TI  - Controlled delivery of transforming growth factor beta1 by self-assembling
      peptide hydrogels induces chondrogenesis of bone marrow stromal cells and
      modulates Smad2/3 signaling.
AB  - Self-assembling peptide hydrogels were modified to deliver transforming growth
      factor beta1 (TGF-beta1) to encapsulated bone-marrow-derived stromal cells
      (BMSCs) for cartilage tissue engineering applications using two different
      approaches: (i) biotin-streptavidin tethering; (ii) adsorption to the peptide
      scaffold. Initial studies to determine the duration of TGF-beta1 medium
      supplementation necessary to stimulate chondrogenesis showed that 4 days of
      transient soluble TGF-beta1 to newborn bovine BMSCs resulted in 10-fold higher
      proteoglycan accumulation than TGF-beta1-free culture after 3 weeks.
      Subsequently, BMSC-seeded peptide hydrogels with either tethered TGF-beta1 (Teth
      TGF) or adsorbed TGF-beta1 (Ads-TGF) were cultured in the TGF-beta1-free medium,
      and chondrogenesis was compared to that for BMSCs encapsulated in unmodified
      peptide hydrogels, both with and without soluble TGF-beta1 medium
      supplementation. Ads-TGF peptide hydrogels stimulated chondrogenesis of BMSCs as
      demonstrated by cell proliferation and cartilage-like extracellular matrix
      accumulation, whereas Teth-TGF did not stimulate chondrogenesis. In parallel
      experiments, TGF-beta1 adsorbed to agarose hydrogels stimulated comparable
      chondrogenesis. Full-length aggrecan was produced by BMSCs in response to Ads-TGF
      in both peptide and agarose hydrogels, whereas medium-delivered TGF-beta1
      stimulated catabolic aggrecan cleavage product formation in agarose but not
      peptide scaffolds. Smad2/3 was transiently phosphorylated in response to Ads-TGF
      but not Teth-TGF, whereas medium-delivered TGF-beta1 produced sustained
      signaling, suggesting that dose and signal duration are potentially important for
      minimizing aggrecan cleavage product formation. Robustness of this technology for
      use in multiple species and ages was demonstrated by effective chondrogenic
      stimulation of adult equine BMSCs, an important translational model used before
      the initiation of human clinical studies.

PMID- 20672993
TI  - Short communication: Inadequate vitamin D exacerbates parathyroid hormone
      elevations in tenofovir users.
AB  - Parathyroid hormone (PTH) elevations are associated with reduced bone mineral
      density and adverse health outcomes and have been reported in patients with HIV
      infection. We aimed to examine the impact of vitamin D status and tenofovir (TDF)
      use on PTH levels among HIV-infected patients receiving combination
      antiretroviral therapy (cART). Demographics, medication and supplement use, and
      clinical data, including 25-hydroxyvitamin D [25(OH)D] and PTH, were collected on
      45 HIV-infected men on ART. Suboptimal vitamin D status was defined as 25(OH)D <
      30 ng/ml. The relationship between antiretroviral agents, suboptimal 25(OH)D, and
      PTH levels was examined. Among subjects with suboptimal vitamin D status, PTH
      values greater than or equal to the ULN (87 pg/ml) were more common among TDF
      users than nonusers: 41% versus 0% (p = 0.018); and median PTH was higher in TDF
      users: 80 pg/ml versus 55 pg/ml (p = 0.02). Among TDF users, PTH was higher in
      the group with suboptimal 25(OH)D (p = 0.045). Multivariable linear regression
      showed that PTH was independently and directly related to TDF use (p = 0.017) and
      inversely related to 25(OH)D (p = 0.017). PTH was not related to the estimated
      glomerular filtration rate (p = 0.9). In this cross-sectional study of HIV
      infected men on ART, the use of TDF and the level of 25(OH)D were independently
      associated with PTH levels. Because TDF is a potent and widely used
      antiretroviral drug, information about cofactors that may exacerbate its side
      effects is of significant clinical value.

PMID- 20672994
TI  - Short communication: Comparable safety and efficacy with once-daily versus twice
      daily dosing of lopinavir/ritonavir tablets with emtricitabine + tenofovir DF in
      antiretroviral-naive, HIV type 1-infected subjects: 96 week final results of the
      randomized trial M05-730.
AB  - Sustained viral suppression with antiretroviral therapy improves clinical
      outcomes for HIV-infected individuals. Study M05-730 evaluated the long-term
      antiviral activity, safety, tolerability, emergence of resistance, and compliance
      with once-daily (QD) versus twice-daily (BID) lopinavir/ritonavir (LPV/r)
      combination therapy in treatment-naive, HIV-1-infected subjects through 96 weeks.
      Antiretroviral-naive subjects with HIV-1 RNA levels >1000 copies/ml were
      randomized to LPV/r QD (N = 333) or BID (N = 331) with tenofovir DF and
      emtricitabine. Through 96 weeks, 77 subjects from each group discontinued
      prematurely; adverse or HIV-related events contributed to discontinuation of 36
      subjects overall, with no significant differences between treatment groups. At 96
      weeks, 216 QD subjects (64.9%) and 229 BID subjects (69.2%) had HIV-1 RNA <50
      copies/ml (p = 0.249) by intent-to-treat analysis. Evaluation of the time to
      virologic failure indicated that 85.0% and 80.7% of QD and BID subjects,
      respectively, maintained virologic suppression through 96 weeks (p = 0.638). QD
      subjects demonstrated greater adherence levels. There were no significant
      differences in virologic response when subjects were analyzed according to
      baseline disease state. Emergence of postbaseline resistance mutations occurred
      at similar low rates in each dosing group. Diarrhea was the most common moderate
      to-severe drug-related adverse event reported; the most common Grade 3+
      laboratory abnormalities were elevations of total cholesterol and triglycerides,
      occurring with similar incidence regardless of LPV/r dosing frequency. QD dosing
      of LPV/r was associated with similar durability of viral suppression and low
      rates of genotypic resistance and treatment-limiting adverse events as compared
      with BID dosing in treatment-naive subjects through 96 weeks of treatment.

PMID- 20672995
TI  - Enrollment, retention, and visit attendance in the University of North Carolina
      Center for AIDS Research HIV clinical cohort, 2001-2007.
AB  - Predictors of study retention and scheduled visit attendance in the University of
      North Carolina Center for AIDS Research (UNC CFAR) prospective clinical cohort of
      HIV-infected patients enrolled between 1 January 2001 and 1 January 2008 are
      reported. At study entry, 1636 participants were 32% female, 58% were African
      American, 49% had not received HIV care elsewhere, 71% were receiving or
      initiated combination antiretroviral therapy, and 26% were diagnosed with AIDS,
      with median (quartiles) age of 40 (34; 47) years, distance to clinic of 45 (21;
      70) miles, HIV-1 RNA of 1396 (200; 26,750) copies/ml, and CD4 of 374 (182; 602)
      cells/mm(3). Participants contributed a median of 7 (4; 13) scheduled visits and
      2.25 (1.0; 3.9) years alive under follow-up. During 6134 person-years of follow
      up, 414 participants dropped out and 145 died. Accounting for differences in
      death by participant characteristics, the 6-year cumulative probability of
      retention was 67% [95% confidence limits (CL): 65, 70%], with 6.75 (95% CL: 6.13,
      7.43) drop outs per 100 person-years. In a multivariable Cox proportional hazards
      model, retention was higher among participants who were insured, had not received
      HIV care elsewhere, had controlled HIV viremia, and were living in nonurban areas
      or proximate to the clinic. In a multivariable modified Poisson regression model
      that accounted for differences in drop out and death by participant
      characteristics, visit attendance was higher among older, AIDS-diagnosed, immune
      compromised, and cART-initiated participants. The UNC CFAR clinical cohort has
      ample enrollment with retention and visit attendance modestly influenced by
      factors such as disease severity.

PMID- 20672996
TI  - Functional evaluation of artificial skeletal muscle tissue constructs fabricated
      by a magnetic force-based tissue engineering technique.
AB  - Skeletal muscle tissue engineering is currently applied in a variety of research
      fields, including regenerative medicine, drug screening, and bioactuator
      development, all of which require the fabrication of biomimic and functional
      skeletal muscle tissues. In the present study, magnetite cationic liposomes were
      used to magnetically label C2C12 myoblast cells for the construction of three
      dimensional artificial skeletal muscle tissues by an applied magnetic force.
      Skeletal muscle functions, such as biochemical and contractile properties, were
      evaluated for the artificial tissue constructs. Histological studies revealed
      that elongated and multinucleated myotubes were observed within the tissue.
      Expression of muscle-specific markers, such as myogenin, myosin heavy chain and
      tropomyosin, were detected in the tissue constructs by western blot analysis.
      Further, creatine kinase activity increased during differentiation. In response
      to electric pulses, the artificial tissue constructs contracted to generate a
      physical force (the maximum twitch force, 33.2 MUN [1.06 mN/mm2]). Rheobase and
      chronaxie of the tissue were determined as 4.45 V and 0.72 ms, respectively.
      These results indicate that the artificial skeletal muscle tissue constructs
      fabricated in this study were physiologically functional and the data obtained
      for the evaluation of their functional properties may provide useful information
      for future skeletal muscle tissue engineering studies.

PMID- 20672997
TI  - Incidence of modifying or discontinuing first HAART regimen and its determinants
      in a cohort of HIV-infected patients from Rio de Janeiro, Brazil.
AB  - Studies on the long-term safety and tolerability of HAART are scarce in
      developing countries. HAART has been universally available in Brazil since 1997,
      providing a unique opportunity to evaluate the incidence and risk factors for
      HAART discontinuation or modification. We analyzed retrospective data from 670
      treatment-naive patients followed at the HIV cohort of Evandro Chagas Clinical
      Research Institute, Oswaldo Cruz Foundation, in Rio de Janeiro, Brazil, who first
      received HAART between January 1996 and December 2006. Our four outcomes of
      interest were treatment failure (TF-MOD), short-term toxicity (ST-MOD), long-term
      toxicity (LT-MOD), and overall modification/discontinuation (MOD, composed of TF
      MOD, ST-MOD, LT-MOD, and other reasons). Risk factors were assessed using Cox's
      proportional hazards regression. Incidences of MOD, ST-MOD, LT-MOD, and TF-MOD
      were 28.3, 24.0, 4.0, and 5.6 per 100 persons-years, respectively. MOD was
      observed in 69% of the patients; 40% of the MODs were toxicity related. The risk
      of MOD in the first year of treatment was 32% (95% CI: 28.3-35.5%); the median
      time from HAART initiation to MOD was 14 months (IQR: 3.0-29.5). The most
      frequent reasons for ST-MOD were gastrointestinal; women had a higher hazard for
      ST-MOD. Metabolic toxicity was the most frequent reason for LT- MOD, particularly
      dislipidemia and lipodystrophy. Increased hazard of TF-MOD was observed among
      those with lower CD4(+) lymphocyte counts (<200 cells/mm(3)). Our results
      indicate that toxicities can compromise adherence and thus impact future
      treatment options. This is especially relevant in the context of limited access
      to second and third line treatment regimens.

PMID- 20672998
TI  - Characterization of SIV in the oral cavity and in vitro inhibition of SIV by
      rhesus macaque saliva.
AB  - Human immunodeficiency virus (HIV) infections are rarely acquired via an oral
      route in adults. Previous studies have shown that human whole saliva inhibits HIV
      infection in vitro, and multiple factors present in human saliva have been shown
      to contribute to this antiviral activity. Despite the widespread use of simian
      immunodeficiency virus (SIV)-infected rhesus macaques as models for HIV
      pathogenesis and transmission, few studies have monitored SIV in the oral cavity
      of infected rhesus macaques and evaluated the viral inhibitory capacity of
      macaque saliva. Utilizing a cohort of rhesus macaques infected with SIV(Mac251),
      we monitored virus levels and genotypic diversity in the saliva throughout the
      course of the disease; findings were similar to previous observations in HIV
      infected humans. An in vitro infectivity assay was utilized to measure inhibition
      of HIV/SIV infection by normal human and rhesus macaque whole saliva. Both human
      and macaque saliva were capable of inhibiting HIV and SIV infection. The
      inhibitory capacity of saliva samples collected from a cohort of animals
      postinfection with SIV increased over the course of disease, coincident with the
      development of SIV-specific antibodies in the saliva. These findings suggest that
      both innate and adaptive factors contribute to inhibition of SIV by whole macaque
      saliva. This work also demonstrates that SIV-infected rhesus macaques provide a
      relevant model to examine the innate and adaptive immune responses that inhibit
      HIV/SIV in the oral cavity.

PMID- 20672999
TI  - Prevalence of HTLV-1/2 infections in Spain: A cross-sectional hospital-based
      survey.
AB  - The presence of antibodies to human T-lymphotropic virus (HTLV) types 1 and 2 was
      examined in 5742 sera belonging to consecutive adult outpatients attended during
      June 2008 at 13 different hospitals across Spain. Overall, 58.8% were female.
      Foreigners represented 8% of the study population. Seven individuals were
      seropositive for HTLV-2 (overall prevalence 0.12%). No cases of HTLV-1 infection
      were found. All HTLV-2(+) subjects were Spanish natives, of whom six were
      coinfected with HIV-1 and five with hepatitis C virus (HCV). Moreover, all but
      one of the HTLV-2(+) subjects had been intravenous drug users. In summary, this
      cross-sectional survey suggests that the rate of HTLV infection in Spain is low,
      and is mostly represented by HTLV-2. Infected individuals are generally Spanish
      natives with a prior history of intravenous drug use and are coinfected with HIV
      1 and/or HCV.

PMID- 20673000
TI  - Regenerative therapy and cancer: in vitro and in vivo studies of the interaction
      between adipose-derived stem cells and breast cancer cells from clinical
      isolates.
AB  - Adipose-derived stem cells (ASCs) have been proposed to stabilize autologous fat
      grafts for regenerative therapy, but their safety is unknown in the setting of
      reconstructive surgery after mastectomy. Both bone marrow mesenchymal stem cells
      (MSCs) and ASC have been shown to enhance tumorigenesis of established breast
      cancer cell lines, but primary patient material has not been tested. Here, we ask
      whether ASC promote the in vitro growth and in vivo tumorigenesis of metastatic
      breast cancer clinical isolates. Metastatic pleural effusion (MPE) cells were
      used for coculture experiments. ASC enhanced the proliferation of MPE cells in
      vitro (5.1-fold). For xenograft experiments (100 sorted cells/injection site),
      nonhematopoietic MPE cells were sorted into resting and active populations: CD90+
      resting (low scatter, 2.1%>=2N DNA), CD90+ active (high scatter, 10.6%>=2N DNA),
      and CD90-. Resting CD90+ MPE cells were tumorigenic in 4/40 sites but growth was
      not augmented by ASC. Active CD90+ MPE cells were tumorigenic (17/40 sites) only
      when coinjected with ASC (p=0.0005, chi2 test). The multilineage potentiality and
      MSC-like immunophenotype of ASC were confirmed by flow cytometry, differentiation
      cultures, and immunostaining. The secretome profile of ASC resembled that
      reported for MSC, but included adipose-associated adipsin and the hormone leptin,
      shown to promote breast cancer growth. Our data indicate that ASC enhance the
      growth of active, but not resting tumor cells. Thus, reconstructive therapy
      utilizing ASC-augmented whole fat should be postponed until there is no evidence
      of active disease.

PMID- 20673001
TI  - Transplantation of marrow-derived cardiac stem cells carried in fibrin improves
      cardiac function after myocardial infarction.
AB  - The high death rate of the transplanted stem cells in the infarcted heart and the
      low efficiency of differentiation toward cardiomyocytes influence the outcome of
      stem cell transplantation for treatment of myocardial infarction (MI). Fibrin
      glue (FG) has been extensively used as a cell implantation matrix to increase
      cell survival. However, mechanisms of the effects of FG for stem cell
      transplantation to improve cardiac function are unclear. We have isolated c
      kit+/Sca-1+ marrow-derived cardiac stem cells (MCSCs) from rat bone marrow; the
      cells expressed weakly early cardiac transcription factor Nkx2.5, GATA-4, Mef2C,
      and Tbx5. Effects of FG on survival, proliferation, and migration of MCSCs were
      examined in vitro. Cytoprotective effects of FG were assessed by exposure of
      MCSCs to anoxia. Efficacy of MCSC transplantation in FG was evaluated in the
      female rat MI model. The MCSCs survived well and proliferated in FG, and they may
      migrate out from the edge of FG in the wound and nature state. Acridine
      orange/ethidium bromide staining and lactate dehydrogenase analysis showed that
      MCSCs in FG were more resistant to anoxia as compared with MCSCs alone. In a rat
      MI model, cardiac function was improved and scar area was obviously reduced in
      group of MCSCs in FG compared with group of MCSCs and FG alone, respectively. Y
      chromosome fluorescence in situ hybridization showed that there were more
      survived MCSCs in group of MCSCs in FG than those in group of MCSCs alone, and
      most Y chromosome positive cells expressed cardiac troponin T (cTnT) and connexin
      43 (Cx-43). Cx-43 was located between Y chromosome positive cells and recipient
      cardiomyocytes. Microvessel density in the peri-infarct regions and infarct
      regions significantly increased in group of MCSCs in FG. These results suggest
      that FG provide a suitable microenvironment for survival and proliferation of
      MCSCs and protect cells from apoptosis and necrosis caused by anoxia. MCSCs could
      differentiate into cardiomyocytes after being transplanted in the border of the
      infarcted myocardium and form connections with native cardiomyocytes. FG is
      helpful for MCSC transplantation to repair myocardium and improve cardiac
      function through promoting the survival, migration, and cardiomyogenic
      differentiation of MCSCs and inducing angiogenesis.

PMID- 20673002
TI  - Systematic review and meta-analysis: renal safety of tenofovir disoproxil
      fumarate in HIV-infected patients.
AB  - BACKGROUND: The efficacy of tenofovir disoproxil fumarate (TDF) as part of
      combination antiretroviral treatment (ART) has been demonstrated in several
      randomized, controlled trials. However, an increasing number of case reports
      suggest that TDF use may be associated with significant nephrotoxicity. Our
      objective was to determine the renal safety of TDF-containing ART regimens for
      HIV-infected individuals. METHODS: MEDLINE, EMBASE, Global Health, Scopus, Biosis
      Previews, Cochrane Library, Web of Science, and existing systematic reviews were
      searched. Prospective studies comparing TDF-containing with non-TDF containing
      ART regimens were selected for inclusion. We extracted data on study
      characteristics, participant characteristics, therapeutic interventions, renal
      function, bone density, and fracture rates. RESULTS: A total of 17 studies
      (including 9 randomized, controlled trials) met the selection criteria. Median
      sample size was 517 participants. Constituent ART regimens were diverse. There
      was a significantly greater loss of kidney function among the TDF recipients,
      compared with control subjects (mean difference in calculated creatinine
      clearance, 3.92 mL/min; 95% confidence interval [CI], 2.13-5.70 mL/min), as well
      as a greater risk of acute renal failure (risk difference, 0.7%; 95% CI, 0.2
      1.2). There was no evidence that TDF use led to increased risk of severe
      proteinuria, hypophosphatemia, or fractures. CONCLUSIONS: Although TDF use was
      associated with a statistically significant loss of renal function, the clinical
      magnitude of this effect was modest. Our findings do not support the need to
      restrict TDF use in jurisdictions where regular monitoring of renal function and
      serum phosphate levels is impractical.

PMID- 20673003
TI  - Systematic review and meta-analysis: reminder systems to reduce catheter
      associated urinary tract infections and urinary catheter use in hospitalized
      patients.
AB  - BACKGROUND: Prolonged catheterization is the primary risk factor for catheter
      associated urinary tract infection (CAUTI). Reminder systems are interventions
      used to prompt the removal of unnecessary urinary catheters. To summarize the
      effect of urinary catheter reminder systems on the rate of CAUTI, urinary
      catheter use, and the need for recatheterization, we performed a systematic
      review and meta-analysis. METHODS: Studies were identified in MEDLINE, the
      Cochrane Library, Biosis, the Web of Science, EMBASE, and CINAHL through August
      2008. Only interventional studies that used reminders to physicians or nurses
      that a urinary catheter was in use or stop orders to prompt catheter removal in
      hospitalized adults were included. A total of 6679 citations were identified; 118
      articles were reviewed, and 14 articles met the selection criteria. RESULTS: The
      rate of CAUTI (episodes per 1000 catheter-days) was reduced by 52% (P < .001)
      with use of a reminder or stop order. The mean duration of catheterization
      decreased by 37%, resulting in 2.61 fewer days of catheterization per patient in
      the intervention versus control groups; the pooled standardized mean difference
      (SMD) in the duration of catheterization was -1.11 overall (P = 070), including a
      statistically significant decrease in studies that used a stop order (SMD, -0.30;
      P = .001) but not in those that used a reminder (SMD, -1.54; P = .071).
      Recatheterization rates were similar in control and intervention groups.
      CONCLUSION: Urinary catheter reminders and stop orders appear to reduce the rate
      of CAUTI and should be strongly considered to enhance the safety of hospitalized
      patients.

PMID- 20673004
TI  - PharmaPlant: the new frontier in vaccines. Forward.

PMID- 20673006
TI  - Molecular farming, patents and access to medicines.
AB  - Transgenic plants have several advantages over other expression systems for the
      production of recombinant medicines, including low costs, large-scale production
      and the ability to produce complex multimeric proteins with appropriate post
      translational modifications. Several plant-made pharmaceuticals, including the
      enzyme glucocerebrosidase, insulin and IFN-alpha(2b), are approaching
      commercialization and these developments have been accompanied by considerable
      patenting activity. In the present article, we investigated plant-made
      pharmaceutical patents between the years 2002 and 2008. There was a clear
      downward trend in the number of patents filed between these years and a greater
      number of patents were filed by public sector institutions or inventors than by
      the private sector. The USA dominated patenting activity providing nearly 30% of
      inventors. The majority of patents were for vaccine candidates (55%), followed by
      therapeutics (38%) and antibodies (7%). The relationship of patenting to
      innovation and access to medicines, particularly in the developing world, will be
      discussed.

PMID- 20673007
TI  - Plant-made immunogens and effective delivery strategies.
AB  - Plant systems for the production of recombinant immunogens have the potential to
      overcome obstacles currently impeding the delivery of vaccines to poorer, more
      remote populations by localizing production and reducing associated costs. The
      nature of the future plant-derived vaccine candidates will have an important
      impact on the extent to which universal access to vaccines can be achieved using
      these technologies. In this article, we examine approaches taken to design
      immunogens, expression systems and delivery strategies that are medically
      feasible and immunologically effective while retaining key benefits of a plant
      production platform. We identify three 'target areas' in which plant-made
      immunogens may offer particular advantages over conventional production systems.

PMID- 20673008
TI  - Plant glycans: friend or foe in vaccine development?
AB  - Plants are an attractive platform for the production of N-glycosylated subunit
      vaccines. Wild type glycosylation of plants can be exploited to produce vaccines
      that antigen-presenting cells effectively take up, degrade and present to cells
      of the adaptive immune system. Alternatively, glycoengineered plants can be used
      to produce humanized antigens. Glycoengineering also allows the construction of
      plants that are able to produce vaccines with custom-made N-glycan structures
      aiding the construction of vaccines that can be delivered to antigen-presenting
      cells in a target-oriented approach. The knowledge of innate immune receptors and
      their role in antigen uptake and presentation is rapidly increasing. In this
      article, aspects of plant glycosylation and immunology are reviewed and we
      discuss the possibilities to use this knowledge for the rational design of plant
      expressed vaccines.

PMID- 20673009
TI  - In planta production of plant-derived and non-plant-derived adjuvants.
AB  - Recombinant antigen production in plants is a safe and economically sound
      strategy for vaccine development, particularly for oral/mucosal vaccination, but
      subunit vaccines usually suffer from weak immunogenicity and require adjuvants
      that escort the antigens, target them to relevant sites and/or activate antigen
      presenting cells for elicitation of protective immunity. Genetic fusions of
      antigens with bacterial adjuvants as the B subunit of the cholera toxin have been
      successful in inducing protective immunity of plant-made vaccines. In addition,
      several plant compounds, mainly plant defensive molecules as lectins and
      saponins, have shown strong adjuvant activities. The molecular diversity of the
      plant kingdom offers a vast source of non-bacterial compounds with adjuvant
      activity, which can be assayed in emerging plant manufacturing systems for the
      design of new plant vaccine formulations.

PMID- 20673010
TI  - Transient expression systems for plant-derived biopharmaceuticals.
AB  - In the molecular farming area, transient expression approaches for pharmaceutical
      proteins production, mainly recombinant monoclonal antibodies and vaccines, were
      developed almost two decades ago and, to date, these systems basically depend on
      Agrobacterium-mediated delivery and virus expression machinery. We survey here
      the current state-of-the-art of this research field. Several vectors have been
      designed on the basis of DNA- and RNA-based plant virus genomes and viral vectors
      are used both as single- and multicomponent expression systems in different
      combinations depending on the protein of interest. The obvious advantages of
      these systems are ease of manipulation, speed, low cost and high yield of
      proteins. In addition, Agrobacterium-mediated expression also allows the
      production in plants of complex proteins assembled from subunits. Currently, the
      transient expression methods are preferential over any other transgenic system
      for the exploitation of large and unrestricted numbers of plants in a contained
      environment. By designing optimal constructs and related means of delivery into
      plant cells, the overall technology plan considers scenarios that envisage high
      yield of bioproducts and ease in monitoring the whole spectrum of upstream
      production, before entering good manufacturing practice facilities. In this way,
      plant-derived bioproducts show promise of high competitiveness towards classical
      eukaryotic cell factory systems.

PMID- 20673011
TI  - Plant-derived vaccines and other therapeutics produced in contained systems.
AB  - The use of contained plant systems for the production of biopharmaceuticals
      represents a powerful alternative to current methods, combining the benefits of
      whole-plant systems and cell cultures. In vitro contained production systems
      include plant cell suspensions, hairy root cultures, novel plants grown in
      contained conditions and microalgae. These systems show intrinsic advantages,
      such as control over growth conditions, production in compliance with good
      manufacturing practice and avoidance of political resistance to the release of
      genetically modified field crops. At present, one of the two plant-produced
      vaccine-related products that have gone all the way through production and
      regulatory hurdles derives from tobacco cell suspensions, and the second is a
      human therapeutic enzyme, which is expected to reach commercial development soon
      and derives from carrot suspension cells. In the future, several other products
      from contained systems are expected to reach the clinical trial stage.

PMID- 20673012
TI  - Chloroplasts as expression platforms for plant-produced vaccines.
AB  - Production of recombinant subunit vaccines from genes incorporated in the plastid
      genome is advantageous because of the attainable expression level due to high
      transgene copy number and the absence of gene silencing; biocontainment as a
      consequence of maternal inheritance of plastids and no transgene presence in the
      pollen; and expression of multiple transgenes in prokaryotic-like operons. We
      discuss the core technology of plastid transformation in Chlamydomonas
      reinhardtii, a unicellular alga, and Nicotiana tabacum (tobacco), a flowering
      plant species, and demonstrate the utility of the technology for the production
      of recombinant vaccine antigens.

PMID- 20673013
TI  - Human papillomavirus vaccines in plants.
AB  - Human papillomaviruses are the etiological agents of cervical cancer, one of the
      two most prevalent cancers in women in developing countries. Currently available
      prophylactic vaccines are based on the L1 major capsid protein, which forms virus
      like particles when expressed in yeast and insect cell lines. Despite their
      recognized efficacy, there are significant shortcomings: the vaccines are
      expensive, include only two oncogenic virus types, are delivered via
      intramuscular injection and require a cold chain. Plant expression systems may
      provide ways of overcoming some of these problems, in particular the expense. In
      this article, we report recent promising advances in the production of
      prophylactic and therapeutic vaccines against human papillomavirus by expression
      of the relevant antigens in plants, and discuss future prospects for the use of
      such vaccines.

PMID- 20673014
TI  - Plant-based anti-HIV-1 strategies: vaccine molecules and antiviral approaches.
AB  - The introduction of highly active antiretroviral therapy has drastically changed
      HIV infection from an acute, very deadly, to a chronic, long-lasting, mild
      disease. However, this requires continuous care management, which is difficult to
      implement worldwide, especially in developing countries. Sky-rocketing costs of
      HIV-positive subjects and the limited success of preventive recommendations mean
      that a vaccine is urgently needed, which could be the only effective strategy for
      the real control of the AIDS pandemic. To be effective, vaccination will need to
      be accessible, affordable and directed against multiple antigens. Plant-based
      vaccines, which are easy to produce and administer, and require no cold chain for
      their heat stability are, in principle, suited to such a strategy. More recently,
      it has been shown that even highly immunogenic, enveloped plant-based vaccines
      can be produced at a competitive and more efficient rate than conventional
      strategies. The high variability of HIV epitopes and the need to stimulate both
      humoral neutralizing antibodies and cellular immunity suggest the importance of
      using the plant system: it offers a wide range of possible strategies, from
      single-epitope to multicomponent vaccines, modulators of the immune response
      (adjuvants) and preventive molecules (microbicides), either alone or in
      association with plant-derived monoclonal antibodies, besides the potential use
      of the latter as therapeutic agents. Furthermore, plant-based anti-HIV strategies
      can be administered not only parenterally but also by the more convenient and
      safer oral route, which is a more suitable approach for possible mass
      vaccination.

PMID- 20673015
TI  - Development of plant-based mucosal vaccines against widespread infectious
      diseases.
AB  - Mucosal vaccination is a perspective for the control of infectious diseases,
      since it is capable of inducing humoral and cell-mediated responses. In addition,
      the delivery of vaccines to mucosal surfaces makes immunization practice safe and
      acceptable, and eliminates needle-associated risks. Transgenic plants can be used
      as bioreactors for the production of mucosally delivered protective antigens.
      This technology shows great promise to simplify and decrease the cost of vaccine
      delivery. Herein, we review the development of mucosally administered vaccines
      expressed in transgenic plants. In particular, we evaluate the advantages and
      disadvantages of using plants for the production of mucosal vaccines against
      widespread infectious diseases such as HIV, hepatitis B and TB.

PMID- 20673016
TI  - Plant-based vaccines against human hepatitis B virus.
AB  - Human hepatitis B virus (HBV) causes a communicable disease that spreads
      worldwide and has brought about considerable economic losses due to human
      mortality and morbidity. HBV fails to reproduce in both cell cultures and
      laboratory animals; however, it is known that excess virion surface protein named
      hepatitis B surface antigen (HBsAg) is produced during viral replication and
      circulates in the blood of carriers as noninfectious particles of 22-nm diameter.
      It had been shown that purified HBsAg particles induce an efficient systemic
      immune response after injection. Consequently, subunit HBV vaccines based on
      HBsAg synthesized in yeasts or mammalian cell culture are currently used. Taking
      into account that hepatitis B is a sexually transmitted disease, development of a
      mucosal HBV vaccine would be beneficial. In this article, we analyze the data on
      development of plant-based HBV vaccines.

PMID- 20673017
TI  - Plant-made pharmaceuticals for the prevention and treatment of autoimmune
      diseases: where are we?
AB  - Molecular farming in plants or plant cell cultures represents a viable
      alternative technology that holds great promise for the low-cost and large-scale
      production of recombinant proteins. The particular case of plant-based vaccines
      for the prevention of autoimmune diseases is addressed here, presenting a
      comprehensive overview of the different molecules and expression technologies
      that have been investigated so far in both academia and industry. The potential
      of plants not only as bioreactors but also as delivery systems for
      pharmaceuticals is discussed, and the advantages of oral delivery of autoantigens
      for the induction of immune tolerance are highlighted.

PMID- 20673018
TI  - Current status of plant-made vaccines for veterinary purposes.
AB  - Interest is growing for the use of plant-made vaccines for veterinary purposes
      since the regulatory landscape still enables delivery of either crude extracts or
      minimally processed plant materials to animals for medicinal purposes. In this
      article, we highlight the current research directions taken with four diseases
      considered as important constraints to international trade in animals: avian
      influenza, Newcastle disease, foot-and-mouth disease and diarrheal disease caused
      by enterotoxigenic Escherichia coli. We also discuss appropriate plant production
      platforms with regards to plant species and transformation methodologies,
      possible areas of development, and the remaining challenges for plant-made
      vaccines for veterinary purposes.

PMID- 20673020
TI  - Enhanced biochemical and biomechanical properties of scaffolds generated by flock
      technology for cartilage tissue engineering.
AB  - Natural cartilage shows column orientation of cells and anisotropic direction of
      collagen fibers. However, matrices presently used in matrix-assisted autologous
      chondrocyte implantation do not show any fiber orientation. Our aim was to
      develop anisotropic scaffolds with parallel fiber orientation that were capable
      to support a cellular cartilaginous phenotype in vitro. Scaffolds were created by
      flock technology and consisted of a membrane of mineralized collagen type I as
      substrate, gelatine as adhesive, and parallel-oriented polyamide flock fibers
      vertically to the substrate. Confocal laser scan microscopy demonstrated that
      mesenchymal stem cells (MSCs) adhered and proliferated well in the scaffolds and
      cell vitality remained high over time. Articular chondrocytes seeded in a
      collagen type I gel into flock scaffolds deposited increasing amounts of
      proteoglycans and collagen type II over time. MSC-seeded flock scaffold
      constructs under chondrogenic conditions deposited significantly more
      proteoglycans and collagen type II than MSC collagen type I gel constructs only.
      Biomechanical testing revealed higher initial hardness of flock scaffolds than
      that of a clinically applied collagen type I/III scaffold combined with superior
      relaxation and an increasing hardness in MSC-loaded flock biocomposites during
      chondrogenesis. In conclusion, flock technology allows fabrication of scaffolds
      with anisotropic fiber orientation that mediates superior biomechanical and
      biochemical composition of tissue engineering constructs for cartilage repair.

PMID- 20673021
TI  - The correlation between the internal structure and vascularization of
      controllable porous bioceramic materials in vivo: a quantitative study.
AB  - It is noticeable that porous architectural characteristics of the biomaterials
      play an important role in revascularization of the scaffold. However, there has
      been no consensus regarding the optimal conditions for vascularization, including
      macropore size, shape, interconnection, and the arrangement of macropores, due to
      the failure to accurately control porous structure of biomaterials. To
      investigate the effect of the porous structure parameters on vascularization of
      the biomaterials, an accurate control of these parameters is required. In this
      study, porous beta-tricalcium phosphate (beta-TCP) with accurately controlled
      pore parameters is fabricated by using assembled organic microspheres as
      templates combined with casting technique. Using this technique, we produced a
      series of disk-type beta-TCP with variable pore sizes and variable
      interconnections to evaluate the influence of macropore size and interconnection
      on the vascularization of bioceramic material in vivo. The vascularization of
      beta-TCP implanted in the rabbit model is evaluated by histomorphology and single
      photon emission computed tomography. The results showed that the pore parameters
      affect not only the size of the blood vessels growing into the porous structure
      but also the number of blood vessels formed in the pores of the bioceramic. The
      increase in pore size only resulted in an increase in size of the blood vessels
      growing into the macroporous of the bioceramic scaffolds. However, with the
      increase in size of interconnection, both the size and number of the blood
      vessels formed in the macroporous increased. Therefore, we conclude that the size
      of the interconnections is more important for vascularization in the scaffold
      compared with the pore size. On the other hand, there was no significant
      difference in vascularization in the scaffolds with pores size above 400 MUm, and
      there was no marked increase in extent of vascularization with further increase
      in pore size above 400 MUm, indicating that the upper limit of pore size for
      vascularization is 400 MUm.

PMID- 20673022
TI  - Chondrogenesis and mineralization during in vitro culture of human mesenchymal
      stem cells on three-dimensional woven scaffolds.
AB  - Human mesenchymal stem cells (hMSCs) and three-dimensional (3D) woven poly(E
      caprolactone) (PCL) scaffolds are promising tools for skeletal tissue
      engineering. We hypothesized that in vitro culture duration and medium additives
      can individually and interactively influence the structure, composition,
      mechanical, and molecular properties of engineered tissues based on hMSCs and 3D
      poly(E-caprolactone). Bone marrow hMSCs were suspended in collagen gel, seeded on
      scaffolds, and cultured for 1, 21, or 45 days under chondrogenic and/or
      osteogenic conditions. Structure, composition, biomechanics, and gene expression
      were analyzed. In chondrogenic medium, cartilaginous tissue formed by day 21, and
      hypertrophic mineralization was observed in the newly formed extracellular matrix
      at the interface with underlying scaffold by day 45. Glycosaminoglycan,
      hydroxyproline, and calcium contents, and alkaline phosphatase activity depended
      on culture duration and medium additives, with significant interactive effects
      (all p < 0.0001). The 45-day constructs exhibited mechanical properties on the
      order of magnitude of native articular cartilage (aggregate, Young's, and shear
      moduli of 0.15, 0.12, and 0.033 MPa, respectively). Gene expression was
      characteristic of chondrogenesis and endochondral bone formation, with sequential
      regulation of Sox-9, collagen type II, aggrecan, core binding factor alpha 1
      (Cbfalpha1)/Runx2, bone sialoprotein, bone morphogenetic protein-2, and
      osteocalcin. In contrast, osteogenic medium produced limited osteogenesis. Long
      term culture of hMSC on 3D scaffolds resulted in chondrogenesis and regional
      mineralization at the interface between soft, newly formed engineered cartilage,
      and stiffer underlying scaffold. These findings merit consideration when
      developing grafts for osteochondral defect repair.

PMID- 20673023
TI  - Laser printing of stem cells for biofabrication of scaffold-free autologous
      grafts.
AB  - Stem cells are of widespread interest in regenerative medicine due to their
      capability of self-renewal and differentiation, which is regulated by their three
      dimensional microenvironment. In this study, a computer-aided biofabrication
      technique based on laser-induced forward transfer (LIFT) is used to generate
      grafts consisting of mesenchymal stem cells (MSCs). We demonstrate that (i) laser
      printing does not cause any cell damage; (ii) laser-printed MSC grafts can be
      differentiated toward bone and cartilage; (iii) LIFT allows printing of cell
      densities high enough for the promotion of chondrogenesis; (iv) with LIFT three
      dimensional scaffold-free autologous tissue grafts can be fabricated keeping
      their predefined structure, and (v) predifferentiated MSCs survived the complete
      printing procedure and kept their functionality. We believe that our results will
      find important applications in stem cell biology and tissue engineering. 

PMID- 20673024
TI  - Proliferation and differentiation of mesenchymal stem cell on collagen sponge
      reinforced with polypropylene/polyethylene terephthalate blend fibers.
AB  - Although tissue-engineered scaffolds made from collagen sponge are suitable for
      cell infiltrating, easily supplying oxygen and nutrients to cells, and removing
      the waste products, their mechanical properties are not satisfactory to be used
      as scaffold materials for tissue engineering applications. To improve mechanical
      properties of collagen, a novel porous scaffold for bone tissue engineering was
      prepared with collagen sponge reinforced by polypropylene/polyethylene
      terephthalate (PP/PET) fibers. Collagen solution (6.33 mg/mL) with PP/PET fibers
      (collagen/fiber ratio [w/w]: 1.27, 0.63, 0.42, 0.25) was freeze-dried, followed
      by cross-linking of combined dehydrothermal and glutaraldehyde. A scanning
      electron microscopy-based analysis of surface of the sponges demonstrated that
      the sponge with collagen/fiber <0.25 exhibited homogenous and interconnected pore
      structure with an average pore size of 200 MUm. Incorporation of PP/PET fibers
      significantly enhanced the compressive strength of the collagen sponge.
      Proliferation and osteogenic differentiation of mesenchymal stem cell in collagen
      sponges reinforced with PP/PET fibers incorporation were significantly enhanced
      compared with collagen sponge without PP/PET incorporation. We conclude that
      incorporation of PP/PET fibers not only improves the mechanical properties of
      collagen sponge, but also enables mesenchymal stem cells to positively improve
      their proliferation and differentiation.

PMID- 20673025
TI  - Passive and active in vitro resorption of calcium and magnesium phosphate cements
      by osteoclastic cells.
AB  - Biocements are clinically applied materials for bone replacement in non-load
      bearing defects. Depending on their final composition, cements can be either
      resorbed or remain stable at the implantation site. Degradation can occur by two
      different mechanisms, by simple dissolution (passive) or after osteoclastic bone
      remodeling (active). This study investigated both the passive and active in vitro
      resorption behavior of brushite (CaHPO4 . 2H2O), monetite (CaHPO4), calcium
      deficient hydroxyapatite (CDHA; Ca9(PO4)5HPO4OH), and struvite (MgNH4PO4 . 6H2O)
      cements. Passive resorption was measured by incubating the cement samples in a
      cell culture medium, whereas active resorption was determined during the surface
      culture of multinuclear osteoclastic cells derived from RAW 264.7 macrophages.
      Osteoclast formation was confirmed by showing tartrate resistant acid phosphatase
      (TRAP) activity on CDHA, brushite, and monetite surfaces, as well as by measuring
      calcitonin receptor (CT-R) expression as an osteoclast-specific protein by
      Western blot analysis for struvite ceramics. An absence of passive degradation
      and only marginally active degradation of <0.01% were found for CDHA matrices.
      For the secondary calcium phosphates brushite and monetite, active degradation
      was predominant with a cumulative Ca2+ release of 2.02 (1.20) MUmol during 13
      days, whereas passive degradation released only 0.788 (0.04) MUmol calcium ions
      into the medium. The struvite cement was the most degradable with a passive
      (active) release of 9.26 (2.92) Mg2+ ions and a total weight loss of 4.7% over 13
      days of the study.

PMID- 20673026
TI  - Opposite effects of transforming growth factor-beta1 and vascular endothelial
      growth factor on the degeneration of aortic valvular interstitial cell are
      modified by the extracellular matrix protein fibronectin: implications for heart
      valve engineering.
AB  - The enhancement of valvular interstitial cell (VIC) calcification by transforming
      growth factor-beta1 (TGF-beta1) and the endothelial inducing effect of vascular
      endothelial growth factor (VEGF) have been demonstrated. Here we report the
      modulating properties of extracellular matrix (ECM) modification on VIC
      calcification in the presence of TGF-beta1 and VEGF. Ovine aortic VICs cultured
      on collagen, fibronectin, laminin, or uncoated surfaces were exposed to TGF
      beta1, VEGF, or left untreated. VEGF significantly inhibited the formation of
      calcific nodules independent of ECM Protein coating (p < 0.05). TGF-beta1
      exposition resulted in the formation of calcific nodules on collagen, laminin,
      and uncoated control surfaces. In contrast, fibronectin coating resulted in
      significantly reduced nodule formation despite TGF-beta1 administration. Further,
      we showed a marked increase of apoptotic and dead cells in calcific nodules.
      Overall, our data demonstrate that, an additive protective effect on VICs can be
      achieved by providing specific growth factors or a specific ECM environment.
      Here, VEGF administration inhibited calcification and apoptosis, particularly in
      combination with fibronectin coating. This combination appears to be a promising
      tool for modification of heart valve scaffolds for tissue engineering purposes
      and preclinical trials.

PMID- 20673029
TI  - Approaches to transfusion therapy and iron overload in patients with sickle cell
      disease: results of an international survey.
AB  - To gain an insight into current transfusion and chelation practice in patients
      with sickle cell disease (SCD), a survey of international experts has been
      conducted. The findings demonstrate that general utilization of transfusion
      therapy is low, the primary barrier to treatment being concerns over resultant
      iron overload and the subsequent need for iron chelation therapy. Where patients
      were transfused, many physicians indicated that a high proportion of patients had
      hemosiderosis. As evidence suggests more patients with SCD could benefit from
      regular transfusion therapy, it is apparent that greater awareness of the need to
      monitor and treat iron overload in transfused patients is required.

PMID- 20673027
TI  - Hydrogel microsphere encapsulation of a cell-based gene therapy system increases
      cell survival of injected cells, transgene expression, and bone volume in a model
      of heterotopic ossification.
AB  - Bone morphogenetic proteins (BMPs) are well known for their osteoinductive
      activity, yet harnessing this capacity remains a high-priority research focus. We
      present a novel technology that delivers high BMP-2 levels at targeted locations
      for rapid endochondral bone formation, enhancing our preexisting cell-based gene
      therapy system by microencapsulating adenovirus-transduced cells in nondegradable
      poly(ethylene glycol) diacrylate (PEGDA) hydrogels before intramuscular delivery.
      This study evaluates the in vitro and in vivo viability, gene expression, and
      bone formation from transgenic fibroblasts encapsulated in PEGDA microspheres.
      Fluorescent viability and cytotoxicity assays demonstrated >95% viability in
      microencapsulated cells. ELISA and alkaline phosphatase assays established that
      BMP-2 secretion and specific activity from microencapsulated AdBMP2-transduced
      fibroblasts were not statistically different from monolayer. Longitudinal
      transgene expression studies of AdDsRed-transduced fibroblasts, followed through
      live animal optical fluorescent imaging, showed that microencapsulated cells
      expressed longer than unencapsulated cells. When comparable numbers of
      microencapsulated AdBMP2-transduced cells were intramuscularly injected into
      mice, microcomputed tomography evaluation demonstrated that the resultant
      heterotopic bone formation was approximately twice the volume of unencapsulated
      cells. The data suggest that microencapsulation protects cells and prolongs and
      spatially distributes transgene expression. Thus, incorporation of PEGDA
      hydrogels significantly advances current gene therapy bone repair approaches.

PMID- 20673028
TI  - Assembly and testing of stem cell-seeded layered collagen constructs for heart
      valve tissue engineering.
AB  - Tissue engineering holds great promise for treatment of valvular diseases.
      Despite excellent progress in the field, current approaches do not fully take
      into account each patient's valve anatomical uniqueness, the presence of a middle
      spongiosa cushion that allows shearing of external fibrous layers (fibrosa and
      ventricularis), and the need for autologous valvular interstitial cells. In this
      study we propose a novel approach to heart valve tissue engineering based on
      bioreactor conditioning of mesenchymal stem cell-seeded, valve-shaped constructs
      assembled from layered collagenous scaffolds. Fibrous scaffolds were prepared by
      decellularization of porcine pericardium and spongiosa scaffolds by
      decellularization and elastase treatment of porcine pulmonary arteries. To create
      anatomically correct constructs, we created silicone molds from native porcine
      aortic valves, dried two identical fibrous scaffolds onto the molds, and
      stabilized them with penta-galloyl-glucose a reversible collagen-binding
      polyphenol that reduces biodegradation. The layers were fused with a
      protein/aldehyde scaffold bio-adhesive and neutralized to reduce cytotoxicity.
      Spongiosa scaffolds, seeded with human bone marrow-derived stem cells, were
      inserted within the valve-shaped layered scaffolds and sutured inside the
      original aortic root. The final product was mounted in a heart valve bioreactor
      and cycled in cell culture conditions. Most cells were alive after 8 days,
      elongated significantly, and stained positive for vimentin, similar to native
      human valvular interstitial cells, indicating feasibility of our approach.

PMID- 20673030
TI  - Transfusion and chelation practices in sickle cell disease: a regional
      perspective.
AB  - Although most common in tropical regions, population migration has meant that
      sickle cell disease is now one of the most prevalent genetic diseases worldwide.
      The issues and challenges faced by physicians and patients have been discussed by
      an international group of experts representing 4 key regions: the USA, Europe,
      Latin America, and the Middle East/Africa. Conclusive evidence to support the use
      of transfusion therapy for the prevention of stroke has resulted in key changes
      to patient management in all regions, and increasing numbers of patients are
      benefiting from this management approach. However, it is apparent that
      transfusion therapy is still under-utilized, largely due to concerns over iron
      overload, alloimmunization, limited blood supplies, and, sometimes, due to
      parental refusal. Once transfused, assessment and management of body iron levels
      can be poor, particularly in patients who are intermittently transfused.
      Compliance with chelation therapy regimens is a significant challenge, but new
      therapeutic options are likely to overcome some of the current barriers. Key
      requirements in all regions were considered to be the following: to provide
      greater physician, patient, and family education; to ensure effective transition
      from pediatric to adult care; and to establish national guidelines in order to
      ensure best practice is consistently applied.

PMID- 20673031
TI  - Significance of polymorphisms in the superoxide dismutase-3 gene in COPD: It's
      all about location!

PMID- 20673032
TI  - The endocrinologic changes in critically ill chronic obstructive pulmonary
      disease patients.
AB  - BACKGROUND: Alterations in the neuroendocrine system occur during critical
      illness. Chronic obstructive pulmonary disease (COPD) itself causes hormonal
      changes. The aim of this study was to determine neu roendocrine hormones of COPD
      patients with acute respiratory failure and to investigate the relationship
      between hormonal changes, mortality, and morbidity. METHODS: We enrolled 21
      patients (13 F/8 M) with COPD exacerbation requiring artificial airway support.
      Blood samples were collected on admission to the ICU, and on the day of hospital
      discharge. Eighteen healthy people were included as controls. RESULTS: Female
      patients had lower luteinizing hormone (LH), follicle stimulating hormone (FSH),
      and free triiodothyronine (fT3), and higher prolactin (PRL) levels than controls
      on admission to the ICU (FSH: 70.3 vs. 29.3 mlU/mL; LH: 26.6 vs. 6.8 mlU/mL; fT3:
      2.9 vs. 2.0 pg/mL; PRL: 12.4 vs. 21.3 ng/mL). Male patients had low testosterone
      and TSH and high PRL but only changes in TSH and PRL reached statistical
      significance (testosterone: 3.5 vs. 1.5 ng/mL, TSH: 1.1 vs. 0.5 ulU/mL, PRL: 9.7
      vs. 14.2 ng/mL). Female patients had lower fT3 than males (fT3(female): 2.7 vs.
      fT3(male): 2.0 pg/mL). On follow-up, significantly elevated FSH and fT3 and
      decreased estradiol concentrations were documented among recovered women (FSH:
      28.4 vs. 46.6 mlU/mL, fT3(,): 2.0 vs. 2.6 pg/mL, E(2): 27.7 vs. 19.0 pg/mL).
      Patients had high C-reactive protein levels and acute physiologic and chronic
      health evaluation II scores. Mortality rate was 9.5% and a negative correlation
      between E(2) and duration of noninvasive mechanical ventilation and length of
      hospital stay was found in male patients. CONCLUSION: Men and women with acute
      respiratory failure in the presence of COPD develop significant changes in the
      neuroendocrine axis. Hormonal suppression vanishes with disease improvement.

PMID- 20673033
TI  - Relation between quality of life and morbidity and mortality in COPD patients:
      Two-year follow-up study.
AB  - Quality of life (QoL) is being recognized as an important outcome when evaluating
      chronic obstructive pulmonary disease (COPD) patients. This study aims at
      identifying the relation between QoL parameters and mortality and morbidity in
      COPD patients by using the St. George Respiratory Questionnaire (SGRQ). In this
      prospective study, 251 COPD patients as defined by American Thoracic Society
      (ATS) criteria were included. A total of 218 patients (86.85%) were male and mean
      age was 65.55 years. A pulmonary function test (PFT) and SGRQ were performed at
      the beginning, first, and second years. During a two-year follow-up, the first
      exacerbation day, the number of exacerbations and intubations, the number and
      duration of hospitalizations, hospitalizations in an intensive care unit, and
      exitus day were recorded. When the correlation between FEV(1), SGRQ scores, and
      these parameters was investigated, there was significant correlation between
      these parameters, and this correlation was more significant in SGRQ scores than
      FEV(1) (Pearson correlation test). The activity score of SGRQ was found to be
      more useful than other scores (Cox regression analysis). Not only PFT but also
      QoL questionnaires are useful in determining the prognosis of COPD. QoL
      questionnaires provide a valid and standardized estimate of the overall impact of
      COPD, and can complement spirometric measurements of baseline assessment of
      patients in routine practice.

PMID- 20673034
TI  - Factors discriminating spontaneous pursed-lips breathing use in patients with
      COPD.
AB  - Pursed-lips breathing (PLB) is often spontaneously performed by chronic
      obstructive pulmonary disease (COPD) patients. The aim of this study was to
      evaluate spontaneous PLB prevalence and to identify factors discriminating its
      use. Fifty-seven patients with COPD (FEV(1) = 44.3 +/- 17.4%pred) underwent
      pulmonary function testing and two incremental bicycle exercise tests. Peak
      workload (Wpeak), oxygen uptake (VO(2)peak), breathing pattern, and dyspnea (Borg
      scale) were measured in the first exercise test and spontaneous PLB performance
      in the second. Six patients spontaneously performed pursed-lips breathing during
      rest (PLBrest), exercise and recovery, 18 during exercise and recovery (PLBex), 7
      during recovery only (PLBrec), 20 not at all (PLBno), and 6 performed other
      expiratory resistive maneuvers. PLBrest and PLBex patients exhibited a lower
      Wpeak, O(2) uptake, and minute ventilation (V(E)), greater expiratory flow
      limitation and higher slopes relating dyspnea to V(E) or W (%predicted). PLBrest
      patients were more hypercapnic, had a lower exercise tolerance and diffusion
      capacity, and greater flow limitation and hyperinflation. PLBrec and PLBno
      patients were indistinguishable with regard to pulmonary function, dyspnea, and
      exercise performance. The most significant independent predictors of spontaneous
      PLB use during exercise were FEV(1)/FVC and the slope relating dyspnea to V(E).
      Spontaneous PLB is most often performed by COPD subjects when ventilation is
      stimulated by exercise, and during recovery from exercise. Severity of airflow
      obstruction and the dyspnea experienced during exercise play an important role in
      determining whether or not PLB is spontaneously performed by COPD patients.

PMID- 20673036
TI  - Pathophysiology of evolution of small airways disease to overt COPD.
AB  - BACKGROUND: The slope of phase III (single breath nitrogen test), an index of
      ventilation inhomogeneity, has been used for early detection of COPD. Tidal
      airway closure (cyclic opening and closure of the peripheral airways during tidal
      breathing; AC(T)) and expiratory flow limitation (attainment of maximal
      expiratory flow during tidal expiration; EFL(T)) cause small airways disease
      (SAD). The relationships of these indices with COPD severity may reflect the
      progress from SAD to overt COPD. METHODS: In this cross-sectional study we have
      assessed for the first time the phase III slope, AC(T) and EFL(T) in 10 smokers
      with normal spirometry (group O) and 40 COPD patients with GOLD scores from I to
      IV. RESULTS: In most group O smokers the phase III slope was increased, and
      further increased with GOLD severity (up to 800%pred in GOLD IV). A close
      correlation was found of slope with GOLD (r = 0.77). AC(T) was absent in smokers
      with normal spirometry and in most patients with mild COPD. EFL(T) first appeared
      in GOLD II patients and its prevalence progressively increased in GOLD III and IV
      patients. CONCLUSIONS: Most group O smokers exhibit increased phase III. With
      overt COPD there is a progressive increase in phase III and reduction of
      FEV(1)/FVC ratio from GOLD I to IV. A reduction of FEV(1) occurs from GOLD stage
      II. As the disease progresses from moderate to severe, there is an increasing
      presence of AC(T). Tidal EFL, with dynamic hyperinflation and severe dyspnea is
      present only in GOLD III and IV.

PMID- 20673035
TI  - Polymorphisms in the superoxide dismutase-3 gene are associated with emphysema in
      COPD.
AB  - Superoxide dismutase-3 (SOD3) is a major extracellular antioxidant enzyme, and
      previous studies have indicated a possible role of this gene in chronic
      obstructive pulmonary disease (COPD). We hypothesized that polymorphisms in the
      SOD3 gene would be associated with COPD and COPD-related phenotypes. We genotyped
      three SOD3 polymorphisms (rs8192287 (E1), rs8192288 (I1), and rs1799895 (R213G))
      in a case-control cohort, with severe COPD cases from the National Emphysema
      Treatment Trial (NETT, n = 389) and smoking controls from the Normative Aging
      Study (NAS, n = 472). We examined whether the single nucleotide polymorphisms
      (SNPs) were associated with COPD status, lung function variables, and
      quantitative computed tomography (CT) measurements of emphysema and airway wall
      thickness. Furthermore, we tried to replicate our initial findings in two family
      based studies, the International COPD Genetics Network (ICGN, n = 3061) and the
      Boston Early-Onset COPD Study (EOCOPD, n = 949). In NETT COPD cases, the minor
      alleles of SNPs E1 and I1 were associated with a higher percentage of emphysema
      (%LAA950) on chest CT scan (p = .029 and p = .0058). The association with E1 was
      replicated in the ICGN family study, where the minor allele was associated with
      more emphysema (p = .048). Airway wall thickness was positively associated with
      the E1 SNP in ICGN; however, this finding was not confirmed in NETT. Quantitative
      CT data were not available in EOCOPD. The SNPs were not associated with lung
      function variables or COPD status in any of the populations. In conclusion,
      polymorphisms in the SOD3 gene were associated with CT emphysema but not COPD
      susceptibility, highlighting the importance of phenotype definition in COPD
      genetics studies.

PMID- 20673037
TI  - Frequent chronic obstructive pulmonary disease exacerbators: how much real, how
      much fictitious?
AB  - Exacerbations are important events in the natural history of chronic obstructive
      pulmonary disease (COPD). The higher the number of COPD exacerbations, the worse
      are the clinical and economical consequences. The distribution of COPD
      exacerbations is however highly variable. Some patients do not exhibit
      exacerbations at all whereas others suffer frequent events (i.e., "frequent COPD
      exacerbators"). We review the scientific evidence regarding the impact of COPD
      exacerbation frequency and assess whether or not these frequent exacerbators
      represent a unique population of COPD patients with higher morbidity and
      mortality risks. A definition of "frequent COPD exacerbators" is suggested to
      differentiate it from other related terms, such as "treatment failure" and
      "recurrence." The standardization of this terminology seems to be necessary to
      further identify COPD phenotypes in patients who have an individual
      susceptibility to develop frequent exacerbations. It can also be of help to
      refine the most appropriate therapeutic and preventative measures.

PMID- 20673038
TI  - Gamma-glutamyl transferase: the silent partner?
AB  - Glutathione is one of the most abundant proteins in vivo involved in maintaining
      cellular homeostasis and is essential for the regulation of oxidant stress. Gamma
      Glutamyl transferase (GGT) is the first enzyme of the gamma glutamyl cycle that
      regulates the antioxidant glutathione, hence it is a critical enzyme in
      glutathione homeostasis. Recent findings have indicated upregulation of GGT in
      inflammation, increasing antioxidant defence whilst potentially driving
      leukotriene-induced inflammation. GGT is a marker of future comorbid diseases
      consistent with inflammation (and oxidative stress) as a key central
      pathophysiological process. COPD reflects several distinct pathological
      phenotypes. Inflammation (and hence oxidative stress) is influenced by other
      factors such as bacterial colonisation and exacerbations. The increased incidence
      of other co-morbid conditions with systemic inflammation suggests that common
      pathophysiological processes are responsible. Active oxidant stress and hence the
      role of GGT may play a role in these processes. Future studies of systemic and
      local GGT function and genotypes in well characterised patients may lead to a
      better understanding of the processes involved and hence the development of new
      treatment strategies.

PMID- 20673039
TI  - Current perspectives of oxidative stress and its measurement in chronic
      obstructive pulmonary disease.
AB  - Cigarette smoking, the principal aetiology of chronic obstructive pulmonary
      disease (COPD) in the developed countries, delivers and generates oxidative
      stress within the lungs. This imbalance of oxidant burden and antioxidant
      capacity has been implicated as an important contributing factor in the
      pathogenesis of COPD. Oxidative processes and free radical generation orchestrate
      the inflammation, mucous gland hyperplasia, and apoptosis of the airway lining
      epithelium which characterises COPD. Pivotal oxidative stress/pro-inflammatory
      molecules include reactive oxygen species such as the superoxides and hydroxyl
      radicals, pro-inflammatory cytokines including leukotrienes, interleukins, tumour
      necrosis factor alpha, and activated transcriptional factors such as nuclear
      factor kappa-B and activator protein 1. The lung has a large reserve of
      antioxidant agents such as glutathione and superoxide dismutase to counter
      oxidants. However, smoking also causes the depletion of antioxidants, which
      further contributes to oxidative tissue damage. The downregulation of antioxidant
      pathways has also been associated with acute exacerbations of COPD. The delivery
      of redox-protective antioxidants may have preventative and therapeutic potential
      of COPD. Although these observations have yet to translate into common clinical
      practice, preliminary clinical trials and studies of animal models have shown
      that interventions to counter this oxidative imbalance may have potential to
      better manage COPD. There is, thus, a need for the ability to monitor such
      interventions and exhaled breath condensate is rapidly emerging as a novel and
      noninvasive approach in the sampling of airway epithelial lining fluid which
      could be used for repeated analysis of oxidative stress and inflammation in the
      lungs.

PMID- 20673042
TI  - Quantitative evaluation of ocular surface inflammation in patients with different
      grade of conjunctivochalasis.
AB  - PURPOSE: To evaluate and compare HLA-DR expression of conjunctival epithelial
      cells in different grade of conjunctivochalasis (CCh). PATIENTS AND METHODS:
      Thirty patients and seven healthy subjects underwent clinical examination,
      grading of CCh by lid-parallel conjunctival fold (LIPCOF) test, and impression
      cytology of the bulbar conjunctiva. HLA-DR expression was analyzed by flow
      cytometry. Schirmer test, tear break-up time, and vital staining were also
      performed. RESULTS: Patients who presented with mild and moderate CCh showed a
      similar expression of HLA-DR to normal subjects. A significant increase (p <
      0.005) of HLA-DR was found in patients with severe CCh. Positive correlation was
      found between fluorescein staining and HLA-DR expression (r = 0.36, p = 0.009)
      and between lissamine-green staining and HLA-DR expression (r = 0.30, p = 0.027).
      Neither correlation was found between Schirmer test nor break up time and HLA-DR
      expression. CONCLUSION: Inflammation plays a pivotal role on the ocular surface
      of patients with severe CCh. Since mild and moderate CCh HLA-DR expression was
      similar to normal controls, we can speculate that the source of inflammation
      could be the presence of conjunctival folds.

PMID- 20673043
TI  - All-trans retinoic Acid regulates cx43 expression, gap junction communication and
      differentiation in primary lens epithelial cells.
AB  - PURPOSE: To examine the effect of all-trans retinoic acid (ATRA) treatment on
      connexin 43 (Cx43) expression, gap junction intercellular communication (GJIC),
      and cellular differentiation in primary canine lens epithelial cells (LEC).
      METHODS AND MATERIALS: Dose and time-dependent effects of ATRA on Cx43 protein,
      mRNA and GJIC, were assessed by immunoblotting, quantitative reverse
      transcription polymerase chain reaction (qRT-PCR), and scrape loading/dye
      transfer assays, respectively. Expression of beta crystallin was evaluated by
      immunoblotting. RESULTS: Treatment with ATRA at non-cytotoxic concentrations
      significantly increased Cx43 protein, mRNA and GJIC in primary canine LEC.
      Treatment with ATRA for five and seven days increased levels of beta crystallin,
      a protein marker of LEC differentiation. Inhibition of GJIC via pre-treatment
      with a synthetic inhibitor, 18-alpha glycyrrethinic acid (AGA), reduced ATRA
      induced increases in Cx43 and GJIC and partially blocked ATRA-induced beta
      crystallin protein. CONCLUSIONS: Treatment with ATRA significantly increased Cx43
      expression and GJIC in canine LEC, and these effects were associated with
      increased LEC differentiation. Results from this study suggest that functional
      gap junctions may play a role in the modulation of cellular differentiation in
      primary canine LEC.

PMID- 20673044
TI  - Erythropoietin is increased in aqueous humor of glaucomatous eyes.
AB  - PURPOSE: To determine the aqueous concentration of erythropoietin (EPO) in
      patients with and without glaucoma. METHODS: Prospective, comparative control
      study. Concentrations of EPO in the aqueous humor were measured using ELISA kits
      from 75 patients, of whom 55 had glaucoma (14 primary acute angle-closure
      glaucoma, PAACG; 26 primary chronic angle-closure glaucoma, PCACG; 11 primary
      open-angle glaucoma, POAG; 4 neovascular glaucoma, NVG), and 20 had cataract only
      as control. RESULTS: EPO concentrations in eyes with glaucoma (71.0 +/- 12.0
      mU/mL) were significantly higher than those in eyes with cataract (6.4 +/- 0.8
      mU/mL, P < 0.001). There were no significant differences (P = 0.421) between
      PCACG (28.84 +/- 3.9 mU/mL) and POAG (20.2 +/- 2.0 mU/mL); however, EPO
      concentrations in eyes with PAACG (118.5 +/- 14 mU/mL) were significantly higher
      than these two chronic subtypes of glaucoma (P < 0.001, respectively). Unusually
      high EPO concentrations were detected in four eyes with NVG (319.5 +/- 47.7
      mU/mL). No effect of age, gender, different eyes, body mass index of the aqueous
      humor EPO concentration could be detected (P > 0.05). No significant correlation
      was found between aqueous humor and plasma EPO concentrations in PAACG and
      control group (P = 0.285, 0.500, respectively). CONCLUSION: Our prospective study
      suggests that the aqueous humor EPO concentrations are increased in eyes with
      glaucoma.

PMID- 20673045
TI  - Lymphatic vessels correlate closely with inflammation index in alkali burned
      cornea.
AB  - PURPOSE: To study the relationship between corneal lymphangiogenesis and
      inflammation in alkali burned corneas. METHODS: Rat corneal lymphatic and blood
      vessels were labeled and distinguished by whole mount immunofluorescence and 5'
      nase-alkaline phosphatase (5'-NA-ALP) double enzyme-histochemistry. Then,
      lymphatic vessel areas (LVA) and lymphatic vessel counting (LVC) were examined.
      Corneal inflammation was evaluated by inflammation index (IF) grading,
      histopathology, electron microscope, and polymorphonuclear leukocyte (PMN)
      infiltration. The relationship between LVC, LVA, IF, and PMN was examined,
      respectively. In addition, corneal lymphatic vessels of eleven human alkali
      burned corneas were examined by lymphatic vessel endothelial receptor (LYVE-1)
      immunohistochemistry. RESULTS: Corneal lymphangiogenesis occurred on Day 3,
      reached the peak at the end of two weeks, and disappeared five weeks after
      alkaline burns. Both LVA and LVC were strongly and positively correlated with IF
      after corneal alkaline burns. However, the relationship between LVC and PMN,
      between LVA and PMN were significant but converse. Among eleven human alkali
      burned corneas, corneal lymphangiogenesis was present in three corneas.
      CONCLUSIONS: Corneal lymphagiogenesis develops after alkaline burns and
      correlates closely with corneal inflammation.

PMID- 20673046
TI  - Lowering of IOP by echothiophate iodide in pseudophakic eyes with glaucoma.
AB  - PURPOSE: We retrospectively investigated the intraocular pressure (IOP)-lowering
      effects of echothiophate iodide (EI) as adjunctive treatment for pseudophakic
      glaucoma patients who were receiving maximal medical therapy (MMT), including the
      newer class of medications, i.e., prostaglandin analogs, alpha-2 agonists, and
      topical carbonic anhydrase inhibitors. METHODS: The medical records of all
      pseudophakic glaucoma patients (24 eyes) under MMT who received supplementary EI
      0.125% between January 2002 and December 2003 were reviewed. IOP data and number
      of medications before, during and after EI treatment were collected. RESULTS:
      Adding EI to MMT further reduced IOP in 23 of 24 eyes. Three eyes (12.5%) showed
      some lowering of IOP, but not enough to be considered controlled (IOP above the
      target pressure). The mean baseline IOP of 30.4 +/- 8.2 mmHg (median 29 mmHg)
      dropped at final follow-up (11.2 +/- 3.9 months) to 16.6 +/- 4.2 mmHg (median 17
      mmHg, p < 0.0001) in all eyes that had showed effective pressure reduction upon
      the addition of EI. Their IOP rose to 27.7 +/- 8.0 mmHg (median 28 mmHg, p <
      0.001) when EI was discontinued because of commercial non-availability. IOP
      reduction was > or =20% in 18 (75%) eyes and > or =30% (a mean decrease of 16.7
      +/- 8.3mmHg) in 15 eyes (63%). Four eyes (16.6%) required a trabeculectomy
      despite EI supplement. Five eyes were re-challenged with EI when a small amount
      was released for sale: their IOP of 26.6 +/- 7.1 mmHg after the first EI
      discontinuation had dropped to 16.4 +/- 4.3 mmHg (p < 0.0001) and rose to 29.6 +/
      7.1 mmHg when EI was again discontinued. The recorded EI-associated side effects
      were increased miosis in all eyes and headache (8/24 patients), neither of which
      were reasons for discontinuation of the drug in any patient. CONCLUSION: EI
      substantially decreased the IOPs in pseudophakic glaucoma eyes receiving maximal
      medical therapy, including the newer class of medications. This drug may be the
      last resort for post-cataract advanced glaucoma patients and may obviate the need
      for filtering surgery among the very elderly.

PMID- 20673047
TI  - A comparison between subjective refraction and aberrometry-derived refraction in
      keratoconus patients and control subjects.
AB  - PURPOSE: This study compares the differences in the magnitude of the subjective
      refraction and three aberrometry-derived refractions along with visual acuity
      achieved with these refractions in a group of keratoconic patients and age
      matched normal subjects. MATERIALS AND METHODS: Subjective refraction and
      Hartmann-Shack aberrometry was performed on six keratoconus patients and 12
      normal subjects. In addition, the logMAR visual acuity achieved using the
      subjective and aberrometry auto-refraction data were measured in the six
      keratoconic subjects. RESULTS: The subjective and aberrometry-derived spherical
      equivalent refraction data were significantly different in the keratoconus group
      (p = 0.015) but not in the normal group (p = 0.10). In the keratoconic patients,
      subjective refraction data gave better logMAR acuity than the aberrometry-derived
      auto-refraction data. The magnitudes of vertical coma and higher-order RMS (root
      mean square) error showed significant correlations with the subjective refraction
      logMAR visual acuities. Significant correlations were found between the
      magnitudes of manifest vertical coma and higher-order RMS error and the
      difference in the M (the mean equivalent sphere) power vector terms between the
      subjective and aberrometry-derived auto-refraction data in the keratoconic group.
      CONCLUSIONS: The subjective and aberrometry-derived spherical equivalent
      refraction data were significantly different in the keratoconus group. The larger
      the magnitude of the higher-order aberrations in keratoconic eyes, the poorer the
      subjective refraction logMAR acuity and the larger the difference between the
      subjective and aberrometry-derived M power vector terms. Further investigation
      into deriving objective refraction data from aberrometry measurements is
      warranted in keratoconus.

PMID- 20673048
TI  - Pharmacological modification of the epithelial permeability by benzalkonium
      chloride in UVA/Riboflavin corneal collagen cross-linking.
AB  - PURPOSE: To examine the biomechanical effect and the UVA-absorption of a
      riboflavin/UVA cross-linking method, which suggests leaving the epithelium intact
      and applying benzalkonium chloride (BAC) on rabbits' corneas. METHODS: In total,
      32 eyes from 16 rabbits were divided into 4 groups. Group 1 was treated with
      intact epithelium and without BAC. In groups 2 and 3, the epithelium was left
      intact and a hypoosmolar solution of riboflavin that contained BAC 0.02% or 0.04%
      was used. Group 4 was treated according to the standard protocol with mechanical
      debridement of the epithelium. After the treatment of both eyes, the rabbits were
      euthanized to prepare the corneas in order for the determination of the
      riboflavin absorption coefficient and biomechanical properties. RESULTS: The
      absorption coefficients of groups 2, 3, and 4 were significantly increased
      compared to group 1. There were no significant differences between groups 2, 3,
      and 4. Stress-strain values and Young's modulus for groups 2, 3, and 4 were
      significantly increased compared to group 1. The stiffening effects did not
      differ within groups 2, 3, and 4. The resistance to enzymatic digestion was
      significantly increased in groups 2, 3, and 4 as compared to group 1.
      CONCLUSIONS: Treatment with BAC 0.02% induces sufficient epithelial permeability
      for the passage of riboflavin, which enables its stromal diffusion and results in
      increased corneal stiffening after cross-linking as compared to the standard
      protocol. Further safety studies will be required before clinical use.

PMID- 20673049
TI  - Slit-lamp-adapted fourier-domain OCT for anterior and posterior segments:
      preliminary results and comparison to time-domain OCT.
AB  - PURPOSE: To evaluate the diagnostic potential of a slit-lamp (SL)-adapted Fourier
      domain (= spectral radar, SR) optical coherence tomography (OCT)-SL-SR-OCT
      instrument as an in vivo imaging device for use in examinations of the anterior
      and posterior segments. MATERIALS AND METHODS: In a pilot study, 88 eyes from 70
      healthy volunteers and patients were examined using a prototype Fourier-domain SL
      SR-OCT system. Results were compared to those from the following commercially
      available systems: the 1310-nm SL-OCT (Heidelberg Engineering, Heidelberg,
      Germany) for anterior segment and the Stratus OCT (Zeiss Meditec, Jena, Germany)
      for posterior segment imaging. Our SL-SR-OCT provides 1025 axial scans, 5000 Hz
      line-scan frequency, scan length of up to 8 mm, axial depth in air of 3.5 mm, and
      resolution of 9 mum. For posterior visualization, a hand-held 78-diopter
      ophthalmoscopic lens was used. RESULTS: Our SL-SR-OCT system allowed simultaneous
      scanning with direct biomicroscopic and SL imaging of anterior and posterior
      segment structures. Anatomical structures and pathological changes were displayed
      with high resolution and excellent contrast. Measurements of corneal and retinal
      thickness were possible. In comparison to images obtained by the SL-OCT, our SL
      SR-OCT boasted a higher resolution, thus providing more clinically relevant
      details of the corneal epithelium, internal structure of filtering blebs, etc.
      Complete imaging of the chamber angle was limited, however, due to the
      backscattering properties of the sclera at 830 nm. For posterior segment imaging,
      excellent delineation of the macula and optic nerve head details, with a distinct
      portrayal of macular pathology and retinal edema, was possible with SL-SR-OCT.
      CONCLUSION: SL-SR-OCT enables detailed imaging of physiological and pathological
      anterior and posterior segment structures. As a multi-purpose device, it offers a
      wide spectrum of applications, with high-quality OCT-imaging, in a comfortable
      setting without the need to move the patient.

PMID- 20673050
TI  - Pharmacological inhibition of N-methyl d-aspartate receptor promotes secretion of
      vascular endothelial growth factor in muller cells: effects of hyperglycemia and
      hypoxia.
AB  - PURPOSE: To characterize the effect of glutamate receptor activation/inhibition
      on the secretion of vascular endothelial growth factor (VEGF) in retina-specific
      glial (Muller) cells under experimental conditions of hyperglycemia and hypoxia,
      two intrinsic pathologic conditions of diabetic retinopathy. METHODS: Purified
      rat Muller cells were grown in normoglycemic or diabetic-like, hyperglycemic (5.6
      or 25 mM glucose, respectively) culture media under normoxic or chemically
      induced hypoxic conditions. After treatments, cells were incubated with glutamate
      receptor agonists and antagonists and VEGF secretion was determined by ELISA.
      Cell viability was determined by Lactate Dehydrogenase (LDH) secretion-assay and
      Ki67 immunocytochemistry. Activation of the Akt signal transduction pathway was
      assessed by western blot using antibodies against phosphorylated Akt. The bio
      activity of the secreted VEGF was analyzed by western blot with a phospho-VEGF
      receptor 2 specific antibody and an in vitro endothelial cell proliferation
      assay. RESULTS: In control (normoglycemic/normoxic) conditions, N-methyl-D
      aspartate receptor (NMDA-R) antagonists MK801 and AP-5 increased secretion of
      VEGF from Muller cells, and this was not observed after AMPA/kainate receptor
      blockade. VEGF secretion after NMDA-R antagonists was independent of cell
      proliferation or cell lysis and it was maintained in cultures grown in
      hyperglycemia or hypoxia. However, under hyperglycemic and hypoxic conditions,
      the observed phenomenon was impaired. We also determined that NMDA-R blockade
      causes a rapid and sustained increase on Akt phosphorylation, a signaling
      molecule that has been previously linked to VEGF expression. Muller cell-derived
      VEGF was capable of promoting VEGF receptor 2 phosphorylation and proliferation
      of endothelial cells. CONCLUSIONS: Our results show that NMDA-R exert a tonic
      inhibition on VEGF secretion in cultures of rat purified Muller cells and
      indicate that in healthy retina, glutamatergic stimulation could potentially
      contribute to the protective antiangiogenic role of Muller glia. We suggest that
      conditions present on diabetic retinopathy could cause malfunction of control
      points on VEGF synthesis on Muller cells.

PMID- 20673051
TI  - Intraocular properties of a repository urokinase receptor antagonist a36 Peptide
      in rabbits.
AB  - PURPOSE: To evaluate the intraocular properties of A36, a peptide that directly
      antagonizes the cell surface urokinase receptor and so prevents pericellular
      urokinase plasminogen activator activity. METHODS: A total of 41 rabbits were
      used. The toxicity study tested three doses of A36: 1 mg/ eye, 0.3 mg/eye, and
      0.1 mg/eye. At 2 and 12 weeks, eyes were evaluated by ERG and histology.
      Pharmacokinetics were studied in rabbit eyes with the dose of 1 mg/eye in two
      different formulations: a micronized preparation and a non-micronized
      formulation. Eyes were enucleated at months 1, 2, 3, 4, and 5. Vitreous, retina,
      and choroid were collected separately for active A36 analysis. RESULTS: We did
      not find ocular toxicity with low and medium doses. At the highest dose, there
      was a transient toxicity at 2 weeks but was not notable at 3 months. The target
      choroid concentration of A36 was chosen as > or =100 nM. The micronized
      formulation at months 1, 2, and 3 combined, showed variable levels in the choroid
      giving 5/10 (50%) of the therapeutic level; the non-micronized formulation at
      months 4 and 5 combined, gave 6/7 (86%) of the therapeutic level, although this
      difference was not statistically significant. CONCLUSION: A36 appears to be long
      lasting; the non-micronized formulation of A36 gave concentrations above
      therapeutic level in the choroid at months 4 and 5. Optimization of the
      formulation of A36, particularly the particle size, may result in a promising new
      compound for exudative age-related macular degeneration treatment.

PMID- 20673052
TI  - Anti-TNF-alpha treatment: a possible promoter in endogenous uveitis?
      observational report on six patients: occurrence of uveitis following etanercept
      treatment.
AB  - BACKGROUND: TNF-alpha inhibitory drugs are widely used with beneficial effect in
      the treatment of rheumatic diseases, such as juvenile idiopathic arthritis and
      ankylosing spondylitis. Due to the complex immune regulatory function of TNF
      alpha, induction of inflammation in several organs including the eye, skin, and
      gastrointestinal tract has been reported. This report describes the occurrence of
      intraocular inflammation after treatment with the TNF-alpha antagonist
      etanercept. METHODS: In this observational case series, we followed and examined
      six patients receiving etanercept for juvenile idiopathic arthritis, ankylosing
      spondylitis, adult Still's disease, or psoriasis. RESULT: All patients responded
      well to their joint affliction, but developed endogenous uveitis for the first
      time after application of etanercept. Following acute intervention with
      corticosteroids, etanercept was discontinued and instead an antibody-based anti
      TNF treatment using infliximab was instituted. We documented visual acuity before
      and after change from etanercept to treatment with the anti-TNF-alpha antibody
      infliximab. Interestingly, prompt long-term remission (mean 34 months) of uveitis
      without recurrence could be induced in all patients. CONCLUSIONS: Our
      observations may indicate that immunodysregulatory and even proinflammatory
      effects of etanercept are of relevance in clinical practice. Further randomized
      controlled clinical trials are necessary to investigate possible side effects of
      anti-TNF therapy using etanercept and infliximab.

PMID- 20673053
TI  - Retinal-image quality and contrast-sensitivity function in age-related macular
      degeneration.
AB  - PURPOSE: In this article, retinal-image quality and contrast sensitivity were
      measured in 25 patients with age-related macular degeneration (ARMD) and 15
      patients with normal retinal health. MATERIALS AND METHOD: Retinal-image quality
      was evaluated with an objective device based on the double-pass technique, and
      for visual performance we measured the contrast-sensitivity function. RESULTS:
      The results from double-pass device revealed the Strehl ratio to be significantly
      (p < 0.0001) lower for the ARMD group with a 54.3% reduction for 3 mm pupil size
      and a 46.9% reduction for 4 mm. Contrast-sensitivity function for ARMD subjects
      was also significantly lower than for the control group (p < 0.05) with a 38.6%
      reduction. CONCLUSIONS: Patients affected with ARMD showed poorer retinal-image
      quality and visual performance than normal subjects. The use of objective devices
      based on the double-pass technique could be useful for the accurate description
      of the retinal-image quality of ARMD eyes, in which retinal scattering is
      significantly increased.

PMID- 20673054
TI  - Influence of benzalkonium chloride on langerhans cells in corneal epithelium and
      development of dry eye in healthy volunteers.
AB  - PURPOSE: To investigate the influence of benzalkonium chloride (BAC) on corneal
      Langerhans cells (LCs) and on the development of dry eye. METHODS: A randomized
      double-blind clinical trial was performed in 20 healthy volunteers. One eye of
      each subject was treated with a 0.01% BAC solution (and the fellow eye with a
      placebo solution) three times daily for 12 weeks. The distribution and density of
      LCs in the central and peripheral corneal epithelium were evaluated by in-vivo
      confocal laser-scanning microscopy (CLSM). The subjects were monitored for dry
      eye (subjective discomfort, slit-lamp biomicroscopy, tear film break-up time,
      Schirmer's test). RESULTS: In the BAC group, compared with placebo, a marked
      increase in LC density was found in the central cornea at Week 6 and in the
      central and peripheral cornea at Week 12. LC density then decreased again in both
      zones after the end of treatment, falling toward (or even below) baseline levels.
      Significant changes in the LC count relative to baseline were found at Week 12 in
      the central and peripheral cornea in the BAC group as well as in the peripheral
      cornea in the placebo group. LC density in the BAC group increased more rapidly
      in the central than in the peripheral cornea. During therapy the BAC group showed
      no signs of dry eye. CONCLUSION: 12-week application of a 0.01% BAC solution in
      healthy volunteers induces a significant increase in LCs in the central cornea at
      Week 12 without dry-eye changes. The return of LC counts toward (or even below)
      baseline levels just four weeks after the end of BAC administration demonstrates
      the rapid normalization of the inflammatory environment.

PMID- 20673055
TI  - An extract of the pleurotus ostreatus mushroom bolsters the glutathione redox
      system in various organs of aged rats.
AB  - This study is to investigate the putative effect of an extract of the oyster
      mushroom, Pleurotus ostreatus, on reduced glutathione (GSH) and its metabolic
      enzymes in major organs of male albino rats. A significant (P < .05) decrease in
      the level of GSH was observed in liver, kidneys, heart, and brain of aged rats
      compared to young rats. Activities of glutathione S-transferase (GST),
      glutathione reductase (GR), and glucose 6-phosphate dehydrogenase (G6PDH) were
      significantly (P < .05) lower in the liver, kidneys, heart, and brain of aged
      rats. The isoform pattern of these enzymes in aged rats also revealed variations
      in relative concentrations, presumably due to oxidative stress during aging.
      Administration of the extract of P. ostreatus to aged rats resulted in a
      significant (P < .05) increase in the levels of GSH and elevated activities of
      GST, GR, and G6PDH in liver, kidney, heart, and brain tissues. An increased
      staining intensity of isoforms of GST and G6PDH was also noted in aged rats that
      had been treated with the mushroom extract compared to aged untreated rats. The
      results of this study may suggest that an extract of P. ostreatus, a potential
      antioxidant, can prevent the oxidation of GSH and protect its related enzymes
      during aging.

PMID- 20673056
TI  - Anti-obesity and hypolipidemic effects of Lycium chinense leaf powder in obese
      rats.
AB  - This study aimed to elucidate the obesity control, hypolipidemic, and antioxidant
      effects of Lycium chinense leaf powder intake by obese rats. Obesity was induced
      in rats through 13 weeks of high-fat diet. The obese rats were then divided into
      four different groups, which were fed for 8 weeks with general diet (G), high-fat
      diet (F), 5% L. chinense leaf powder with a high-fat diet (FLP5), or 10% L.
      chinense leaf powder with a high-fat diet (FLP10). The body weight gain of the
      FLP5 group was significantly lower than that of the F group. Also, the obesity
      index of the FLP5 and FLP10 group was significantly lower than that of the F
      group. Serum triglyceride and low-density lipoprotein (LDL)-cholesterol levels in
      the FLP5 group were significantly lower than those of the F group. The intake of
      L. chinense leaf powder did not seem to significantly affect the levels of serum
      homocysteine, leptin, and ghrelin compared to the control group without L.
      chinense leaf powder intake. The glutathione content in the liver was
      significantly higher in the FLP5 group than in the G group, but the glutathione S
      transferase activity was significantly lower than in the F group. The
      thiobarbituric acid-reactive substances levels in the liver and kidney were
      relatively lower in the FLP5 and FLP10 groups than in the G group. In summary,
      intake of L. chinense leaf powder in obese rats coincided with a lowering of body
      weight and levels of serum triglyceride and LDL-cholesterol. It also displayed
      antioxidant effects.

PMID- 20673057
TI  - The antioxidant effects of genistein are associated with AMP-activated protein
      kinase activation and PTEN induction in prostate cancer cells.
AB  - Epidemiological evidence suggests a lower incidence of prostate cancer in Asian
      countries, where soy products are more frequently consumed than in Western
      countries, indicating that isoflavones from soy have chemopreventive activities
      in prostate cells. Here, we tested the effects of the soy isoflavone genistein on
      antioxidant enzymes in DU145 prostate cancer cells. Genistein significantly
      decreased reactive oxygen species levels and induced the expression of the
      antioxidant enzymes manganese (Mn) superoxide dismutase (SOD) and catalase, which
      were associated with AMP-activated protein kinase (AMPK) and phosphatase and
      tensin homolog deleted from chromosome 10 (PTEN) pathways. The induced expression
      of catalase, MnSOD, and PTEN were attenuated by pretreatment with a
      pharmacological inhibitor for AMPK, indicating the effects of genistein primarily
      depend on AMPK. Furthermore, PTEN is essential for genistein activity, as shown
      by PTEN transfection in PTEN-deficient PC3 cells. Thus, genistein induces
      antioxidant enzymes through AMPK activation and increased PTEN expression.

PMID- 20673058
TI  - Anti-inflammatory effect of Taraxacum officinale leaves on lipopolysaccharide
      induced inflammatory responses in RAW 264.7 cells.
AB  - To investigate the efficacy and the mechanism of the anti-inflammatory effect of
      Taraxacum officinale leaves (TOLs), the effect of a methanol extract and its
      fractions recovered from TOLs on lipopolysaccharide (LPS)-induced responses was
      studied in the mouse macrophage cell line, RAW 264.7. Cells were pretreated with
      various concentrations of the methanol extract and its fractions and subsequently
      incubated with LPS (1 microg/mL). The levels of nitric oxide (NO), prostaglandin
      (PG) E(2), and pro-inflammatory cytokines including tumor necrosis factor (TNF)
      alpha, interleukin (IL)-1beta, and IL-6 were determined using enzyme-linked
      immunosorbent assays. Expressions of inducible NO synthase (iNOS) and
      cyclooxygenase (COX)-2 and activation of mitogen-activated protein (MAP) kinases
      were analyzed using western blotting. The methanol extract and its fractions
      inhibited LPS-induced production of NO, pro-inflammatory cytokines, and PGE(2) in
      a dose-dependent manner. The chloroform fraction significantly suppressed
      production of NO, PGE(2), and two pro-inflammatory cytokines (TNF-alpha and IL
      1beta) in a dose-dependent manner with 50% inhibitory concentration values of
      66.51, 90.96, 114.76, and 171.06 microg/mL, respectively. The ethyl acetate
      fraction also inhibited production of the inflammatory molecules. The chloroform
      and ethyl acetate fractions reduced LPS-induced expressions of iNOS and COX-2 and
      activation of MAP kinases in a dose-dependent manner. Among the fractions of the
      methanol extract, the chloroform and ethyl acetate fractions exhibited the most
      effective anti-inflammatory activities. These results show that the anti
      inflammatory effects of TOLs are probably due to down-regulation of NO, PGE(2),
      and pro-inflammatory cytokines and reduced expressions of iNOS and COX-2 via
      inactivation of the MAP kinase signal pathway.

PMID- 20673059
TI  - Anti-inflammatory activity of select sorghum (Sorghum bicolor) brans.
AB  - The bran fractions of certain varieties of sorghum (Sorghum bicolor) grain are
      rich sources of phytochemicals and antioxidants. In this article, the anti
      inflammatory actions of extracts of select sorghum brans were evaluated in two
      experimental inflammatory systems: (1) the release of cytokines by
      lipopolysaccharide-activated peripheral blood mononuclear cells and (2) 12-O
      tetradecanoylphorbol acetate (TPA)-induced ear edema in mice. A 1:200 dilution of
      a 10% (wt/vol) ethanol extract of black sorghum bran significantly inhibited the
      secretion of the pro-inflammatory cytokines interleukin-1beta and tumor necrosis
      factor-alpha. Ethanolic extracts of both black and sumac varieties of sorghum
      bran significantly reduced edema in inflamed ears as measured by ear thickness
      and ear punch weight 6 hours following TPA application. The degree of inhibition
      was similar to that observed with indomethacin. Black sorghum bran significantly
      diminished the increase in myeloperoxidase activity 24 hours following the
      application of TPA. No anti-inflammatory activity was observed with white and
      Mycogen sorghum bran varieties or with oat, wheat, or rice brans in the mouse ear
      model. The anti-inflammatory activity observed with these brans correlated with
      their phenolic content and antioxidant activity. These results demonstrate that
      select sorghum bran varieties possess significant anti-inflammatory activity.

PMID- 20673060
TI  - Nephroprotective activity of Prosthechea michuacana against cisplatin-induced
      acute renal failure in rats.
AB  - In Mexican traditional medicine the orchid Prosthechea michuacana is highly
      valued as a food and in the treatment of various human diseases, including drug
      related renal disease. Methanol, hexane, and chloroform extracts of bulbs of P.
      michuacana were studied in the cisplatin-induced renal injury model in rats.
      Results showed that treatment with cisplatin induced significant elevations in
      concentrations of blood urea and serum creatinine and in lipid peroxidation.
      Treatments with methanolic extract (200, 400 and 500 mg/kg) increased levels of
      biochemical markers of renal injury like reduced glutathione, glutathione S
      transferase, and superoxide dismutase and inhibited the increases in blood urea
      and serum creatinine concentrations and lipid peroxidation induced by cisplatin.
      Hexane and chloroform extracts did not show any effect. The results obtained in
      the present study indicate that this orchid can be a potential source of natural
      nephroprotective activity.

PMID- 20673061
TI  - Pharmacokinetics and tissue distribution of 14C-labeled grape polyphenols in the
      periphery and the central nervous system following oral administration.
AB  - Grape polyphenols confer potential health benefits, including prevention of
      neurodegenerative diseases. To determine the absorption and tissue distribution
      of the complex grape polyphenol mixture, (14)C-labeled polyphenols were
      biosynthesized by grape cell suspension cultures, during co-incubation with
      radioisotopically labeled sucrose, and fractionated into polyphenolic
      subfractions. The pharmacokinetics and distribution of grape polyphenols into
      blood, brain, and peripheral interstitial fluid were determined by tracking the
      (14)C label. The blood peak (14)C concentration of the fractions ranged from 15
      minutes to 4 hours. Absorption and tissue distribution varied greatly between
      fractions. Concentrations in interstitial fluid were lower than in blood. The
      amount of residual label in the brain at 24 hours ranged from 0.1% to 1.7% of the
      dose, depending on the fraction. (14)C label found in the brain tissue and brain
      microdialysate indicated that grape polyphenols or their metabolites are able to
      cross the blood-brain barrier. Using (14)C-labeled plant polyphenols it is
      possible to track the compounds or their metabolic products into any tissue and
      determine distribution patterns in spite of low concentrations. A central
      question regarding the potential role of dietary polyphenolics in
      neurodegenerative research is whether they are bioavailable in the brain. Our
      observations indicate that some grape-derived polyphenolics do reach the brain,
      which suggests their potential value for applications in neurodegenerative
      disorders.

PMID- 20673062
TI  - Lactic acid fermentation of germinated barley fiber and proliferative function of
      colonic epithelial cells in loperamide-induced rats.
AB  - To develop a functional food from the dietary fiber fraction of germinated barley
      (Hordeum vulgare L.) (GBF), lactic acid fermentation was attempted using
      Lactobacillus acidophilus, Streptococcus thermophilus, and Bifidobacterium
      bifidus. The quality characteristics of the lactic acid-fermented product and its
      effect on gastrointestinal function in an animal model were examined. The
      anaerobic fermentation of 1% and 2% GBF yielded lactic acid bacteria at 8.9 +/-
      1.0 x 10(8) and 1.6 +/- 0.2 x 10(9) colony-forming units/mL, and it was
      considered acceptable for consumption by sensory assessment. To determine the
      effect on gastrointestinal function, Sprague-Dawley rats were fed with three
      types of diets: a normal chow diet and chow diets supplemented with 10% lactic
      acid bacteria or a yogurt fermented with 2% GBF (GBFY). The rats fed GBFY for 6
      weeks gained less body weight, excreted more fecal mass, and had improved
      gastrointestinal transit as examined with barium sulfate. The effect of GBFY on
      colonic epithelial proliferation was investigated through loperamide (LPM)
      induced constipation in rats. The rats fed with GBFY for 6 weeks were
      intraperitoneally administered LPM twice daily for 7 days. GBFY supplementation
      decreased fecal excretion and moisture content in feces and depleted goblet cells
      as observed by hematoxylin and eosin stain. However, the rats supplemented with
      GBFY prior to the LPM administration had enhanced bowel movement, mucin
      secretion, and production of short-chain fatty acids compared with values for the
      LPM-alone group. Immunohistochemistry revealed that the GBFY supplement increased
      the numbers of nuclei stained positively for Ki-67 and extended from the base to
      the middle zone of crypts. These results indicate that GBFY alleviates
      constipation via the proliferation of the colonic crypts in LPM-administered
      rats.

PMID- 20673063
TI  - Protective effect of naringin, a citrus flavonoid, against colchicine-induced
      cognitive dysfunction and oxidative damage in rats.
AB  - Alzheimer's disease is a neurodegenerative disorder. Central administration of
      colchicine is well known to cause cognitive impairment and oxidative damage,
      which simulates sporadic dementia of the Alzheimer type in humans. The present
      study has been designed to investigate the protective effects of naringin against
      the colchicine-induced cognitive impairment and oxidative damage in rats.
      Colchicine (15 microg/5 microL), administered intracerebroventricularly, resulted
      in poor memory retention in both the Morris water maze and elevated plus maze
      task paradigms and caused marked oxidative damage. It also caused a significant
      decrease in acetylcholinesterase activity. Naringin (40 and 80 mg/kg, p.o.)
      treatment was given daily for a period of 25 days beginning 4 days prior to
      colchicine administration. Chronic treatment with naringin caused significant
      improvement in the cognitive performance and attenuated oxidative damage, as
      evidenced by lowering of malondialdehyde level and nitrite concentration and
      restoration of superoxide dismutase, catalase, glutathione S-transferase, and
      reduced glutathione levels, and acetylcholinesterase activity compared to
      control. The present study highlights the therapeutic potential of naringin
      against colchicine-induced cognitive impairment and associated oxidative damage.

PMID- 20673064
TI  - A vision for 21st century U.S. Policy to support sustainable advancement of
      scientific discovery and technological innovation.

PMID- 20673065
TI  - Performance of a North American field population and a laboratory colony of the
      potato tuberworm, Phthorimaea operculella, on foliage of resistant and
      susceptible potato clones.
AB  - Foliar resistance of two potato clones was tested against a Columbia Basin field
      population (CBFP) and a Colorado laboratory colony (COLC) of the potato
      tuberworm, Phthorimaea operculella (Zeller) (Lepidoptera: Gelechiidae). The first
      clone was a cross of a cultivated potato, Solanum tuberosum L. (Solanales:
      Solanaceae), and a wild potato, Solanum berthaultii Hawkes (Q 174-2); the second
      clone was cv. Allegany, S. tuberosum L.. In no-choice assays, defoliation by P.
      operculella larvae of COLC and CBFP did not differ on Allegany and Q174-2. Larval
      weight and production of COLC and CBFP colonies were similarly reduced on Q174-2
      compared to cv. Allegany, although larval weights and production of the CBFP
      population were slightly less affected by the host. Larval production by the COLC
      on Allegany was greater than that on Q174-2, while that of the CBFP on Allegany
      and Q174-2 did not differ. However, production of P. operculella larvae by the
      CBFP on Q174-2 during no-choice assays was greater than that in choice tests,
      indicating reduced host preference. Most of the larvae recovered from either host
      were fourth instars, followed by third instars. Although the levels of resistance
      expressed by Q174-2 potato clone to the two P. operculella populations differed
      in magnitude, nearly all of P. operculella performance criteria measured in this
      study were adversely affected by Q174-2 foliage compared to the commercial potato
      cultivar, cv. Allegany.

PMID- 20673066
TI  - The effect of the landscape matrix on the distribution of dung and carrion
      beetles in a fragmented tropical rain forest.
AB  - Understanding the response of species to anthropogenic landscape modification is
      essential to design effective conservation programs. Recently, insects have been
      used in empirical studies to evaluate the impact of habitat modification and
      landscape fragmentation on biological diversity because they are often affected
      rapidly by changes in land use. In this study, the use of the landscape matrix by
      dung and carrion beetles in a fragmented tropical rain forest in the Los Tuxtlas
      Biosphere Reserve was analyzed. Fragments of tropical rain forest, forest-pasture
      edges, pastures, isolated trees, living fences (trees connected with barbed wire)
      and barbed wire fences were studied both near and far from forest fragments.
      Forest fragments had the highest abundance values, but pastures had the highest
      dung and carrion beetle biomass. Habitat specificity was high for the beetles in
      the most dissimilar habitats. Forest fragments and forest-pasture edges had and
      shared the highest number of species, but they shared only two species with
      pastures, barbed wire fences and isolated trees. Only one forest species was
      found within living fences far from the forest fragments. However, approximately
      37% of the forest species were caught within living fences near the forest
      fragments. Therefore, forest-pasture edges function as hard edges and prevent
      movement among forest fragments, but living fences seem to act as continuous
      habitat corridors when connected to forest fragments, allowing forest beetles to
      move between the fragments. Further studies are necessary to determine the
      minimum width of living fences necessary to provide good corridors for these
      beetles and other species.

PMID- 20673067
TI  - Specialized prey selection behavior of two East African assassin bugs, Scipinnia
      repax and Nagusta sp. that prey on social jumping spiders.
AB  - The prey choice behavior and predatory strategies of two East African assassin
      bugs, Scipinnia repax (Stal 1961) and Nagusta sp. (Hemiptera: Reduviidae), were
      investigated in the field and the laboratory. Both of these species are from the
      subfamily Harpactorinae and specialize in eating spiders. They prey especially
      often on social jumping spiders (Salticidae) that build nest complexes (nests
      connected by silk) in vegetation near the shoreline of Lake Victoria. Both
      reduviid species associate with these nest complexes and prey on the resident
      salticids. Nagusta sp., but not S. repax, form groups on nest complexes with 2-3
      individuals of Nagusta sometimes feeding together on a single salticid. In
      addition to social salticids, Nagusta sp. preys on Portia africana, an
      araneophagic salticid that often invades the same nest complexes. S. repax preys
      on salticid eggs and also on Nagusta. Although they avoid ants, Nagusta and
      especially S. repax prey on ant-mimicking salticids, suggesting that sensory
      modalities other than vision play a dominant role in prey detection.

PMID- 20673068
TI  - Cold hardiness and supercooling capacity in the overwintering larvae of the
      codling moth, Cydia pomonella.
AB  - The codling moth, Cydia pomonella L. (Lepidoptera: Tortricidae), a worldwide
      apple pest, is classified as a freeze-intolerant organism and one of the most
      cold-tolerant pests. The objectives of this study were to examine the
      supercooling point of overwintering and non-diapausing larvae of C. pomonella as
      an index of its cold hardiness, and to assess larval mortality following 24 h
      exposure to extreme low temperatures ranging from -5 to -25 degrees C. The mean
      (+/-SE) supercooling point for feeding larvae (third through fifth instars) was 
      12.4 +/- 1.1 degrees C. The mean supercooling point for cocooned, non-diapausing
      larvae (i.e., non-feeding stages) decreased as the days that the arvae were
      cocooned increased and changed between -15.1 +/- 1.2 degrees C for one to two day
      cocooned arvae and -19.2 +/- 1.8 degrees C for less than five day cocooned
      larvae. The mean (+/-SE) supercooling point for other non-feeding stages
      containing pupae and overwintering larvae were -19.9 +/- 1.0 degrees C and -20.2
      +/- 0.2 degrees C, respectively. Mean supercooling points of C. pomonella larvae
      were significantly lower during the winter months than the summer months, and sex
      had no effect on the supercooling point of C. pomonella larvae. The mortality of
      larvae increased significantly after individuals were exposed to temperatures
      below the mean supercooling point of the population. The supercooling point was a
      good predictor of cold hardiness.

PMID- 20673069
TI  - Identification of RAPD markers linked to digestive amylase genes using near
      isogenic lines of the silkworm, Bombyx mori.
AB  - Digestive amylase has been identified as a useful marker for breeding in the
      silkwrom, Bombyx mori L (Lepidoptera: Bombycidae), due to its wide genetic
      divergence, its role in better digestibility and robustness. The low yielding
      indigenous B. mori breeds of tropics like India are characterized by high
      activity amylase genes controlled by Amy d(iv) or d(v) alleles, while the high
      yielding breeds of temperate origin are endowed with 'null' type (Amy d(n)) with
      low activity. For improving the digestibility and survival of temperate breeds of
      Japanese origin, Near Isogenic Lines (NILs) were developed introgressing the Amy
      d(iv) and d(v) alleles from the Donor Parents (DPs) into the genetic background
      of the Recurrent Parents (RPs) with 'null' type of amylase, which showed
      significant improvement in viability of the NILs. With the objective to know
      whether the amylase gene itself may confer higher survival by improving
      digestibility or some other closely linked genes flanking the amylase locus is
      responsible for better viability of the NILs, RAPD profiles among six B. mori
      breeds comprising of the DPs, RPs, and NILs developed through introgression of
      Amy d(iv) or d(v) alleles were analysed using 27 sets of RAPD primers. Out of the
      27 primers, six (OPA01, OPA06, OPA09, OPA15, OPAH03, and OPAH05) showed RAPD
      products linked to the amylase genes of the DPs introgressed in the NILs, which
      were absent in their respective RPs. Three amplicons of 1584 bp, 1904 bp, and
      1232 bp were specific to Amy d(iv) allele and one amplified product of 1776 bp
      was found to be linked with the Amy d(v) allele. Interestingly, two PCR products
      of 2628 and 1375 bp were associated with both Amy d(iv) and d(v) alleles. The
      results are discussed in light of further characterization of these amplified
      products leading to identification of DNA sequences that may be responsible for
      better digestibility and higher survival in B. mori.

PMID- 20673070
TI  - Differential flight muscle development in workers, queens and males of the
      eusocial bees, Apis mellifera and Scaptotrigona postica.
AB  - The flight capability of the adult eusocial bees, Apis mellifera L. and
      Scaptotrigona postica Latreille (Hymenoptera: Apidae), is intrinsically linked to
      their colonial functions, such as the nuptial flight for mating in the case of
      queens and males, and the exploration of new habitats for nesting and food
      sources in the case of workers. Flight is achieved by the contraction of indirect
      flight muscles that produce changes in thoracic volume and, therefore, wing
      movement. The purpose of this work is to examine possible differences in muscle
      development that may be associated with the flying activity of individuals in a
      given life stage considering the behavioral and physiological differences among
      the stages and between the two species studied. Measurements of the muscle fibers
      obtained from light microscopy preparations of muscle were submitted to
      statistical analysis in order to detect the differences at a given time, or
      throughout the life of the individual. The results show that muscle morphology is
      similar in both species, but in A. mellifera the muscle fibers are thicker and
      more numerous than in S. postica. Differences in the fiber thickness according to
      life stage in all classes of individuals of both species were detected. These
      results are discussed in relation to the need for flying in each life stage.

PMID- 20673071
TI  - Phylogenetic analysis and rapid identification of the whitefly, Bemisia afer, in
      China.
AB  - The phylogenetic relationship between the whitefly Bemisia afer (Priesner &
      Hosny) (Hemiptera: Aleyrodidae) from China and other populations among the world
      were analyzed based on the mitochondrial cytochrome oxidase I (mtCOI) gene.
      Phylogenetic analysis of mtCOI sequences and those of reference B. afer sequences
      showed that the populations of the species could be separated into 5 clades (I
      V). There were at least two clades of the species from China (IV and V). These
      data suggested that B. afer might be a species complex. The Chinese B. afer
      populations were most divergent with B. afer from the United Kingdom and African
      countries. The distance between the Chinese B. afer (IV and V) and clades I, II,
      and III is more than 32%, while the distance among clades I, II, III is lower
      than 7.7%. A new set of primers specific to B. afer was designed to amplify a
      region of approximately 400 bp to discriminate B. afer from other Bemisia species
      in China based on mtCOI sequences.

PMID- 20673072
TI  - Karyotype plasticity in crickets: numerical, morphological, and nucleolar
      organizer region distribution pattern of Anurogryllus sp.
AB  - Within the Orthopteran species, those of the suborder Ensifera have been rarely
      studied from the cytogenetic point of view, mainly due to the difficulties for
      taxonomic identification of its species. The Gryllidae is the second largest
      family of this suborder and possesses some genera, such as Anurogryllus, that
      occur only on the American continents. The aim of this work was to determine the
      karyotype characteristics, the meiotic chromosome behaviour, and the nucleolar
      organizer region (NOR) pattern of Anurogryllus sp (Orthoptera: Gryllidae). In the
      analyzed sample, high levels of numerical, morphological, and NORs polymorphisms
      were detected. Within five distinct karyotypes that were found, the basic
      karyotype of Anurogryllus sp. showed 2n(male symbol) = 22 + X0 with acrocentric
      autosomes and a metacentric X sex chromosome; furthermore, a conspicuous
      secondary constriction related to the NOR was present along the entire short arm
      on pair 5. The other four types of karyotypes arose from centric fusions between
      elements of pairs 1/3, 2/6, 4/7 and a NOR partial translocation from pair 5 onto
      the long arm terminal region of one element of the fused pair 2/6. Such
      intraspecific variability and the consequences of high levels of polymorphism are
      discussed, leading to conjectures about the mechanisms that led to these
      chromosome rearrangements.

PMID- 20673073
TI  - Methods for casting subterranean ant nests.
AB  - The study of subterranean ant nests has been impeded by the difficulty of
      rendering their structures in visible form. Here, several different casting
      materials are shown to make perfect casts of the underground nests of ants. Each
      material (dental plaster, paraffin wax, aluminum, zinc) has advantages and
      limitations, which are discussed. Some of the materials allow the recovery of the
      ants entombed in the casts, allowing a census of the ants to be connected with
      features of their nest architecture. The necessary equipment and procedures are
      described in the hope that more researchers will study this very important aspect
      of ant natural history.

PMID- 20673074
TI  - Effect of emamectin benzoate on mortality, proboscis extension, gustation and
      reproduction of the corn earworm, Helicoverpa zea.
AB  - Newly emerged corn earworm adults, Helicoverpa zea (Boddie) (Lepidoptera:
      Noctuidae) require a carbohydrate source from plant or other exudates and nectars
      for dispersal and reproduction. Adults actively seek and forage at feeding sites
      upon eclosion in the habitat of the larval host plant or during dispersal to, or
      colonization of, a suitable reproductive habitat. This nocturnal behavior of H.
      zea has potential for exploitation as a pest management strategy for suppression
      using an adult feeding approach. This approach entails the use of a feeding
      attractant and stimulant in combination with a toxicant that when ingested by the
      adult will either reduce fecundity/fertility at sub-lethal dosages or kill the
      adult. The intent of this study was to assess reproductive inhibition and
      toxicity of emamectin benzoate on H. zea when ingested by the adults when mixed
      in ppm active ingredient (wt:vol) with 2.5 M sucrose as a feeding stimulant.
      Because the mixture has to be ingested to function, the effect of emamectin
      benzoate was also evaluated at sub-lethal and lethal concentrations on proboscis
      extension and gustatory response of H. zea in the laboratory. Feral males
      captured in sex pheromone-baited traps in the field were used for toxicity
      evaluations because they were readily available and were more representative of
      the field populations than laboratory-reared adults. Laboratory-reared female
      moths were used for reproduction effects because it is very difficult to collect
      newly emerged feral females from the field. Emamectin benzoate was highly toxic
      to feral H. zea males with LC(50) values (95% CL) being 0.718 (0.532-0.878),
      0.525 (0.316-0.751), and 0.182 (0.06-0.294) ppm for 24, 48 and 72 h responses,
      respectively. Sub-lethal concentrations of emamectin benzoate did not
      significantly reduce proboscis extension response of feral males and gustatory
      response of female H. zea. Sublethal concentrations of emamectin benzoate
      significantly reduced percent larval hatch of eggs and mating frequency of female
      H. zea. Larval survival to the pupal stage was also significantly reduced by
      ingestion of emamectin benzoate by female H. zea. These data suggest that
      emamectin benzoate is a useful toxicant in an attract-and-kill control strategy
      against H. zea. Field studies are warranted to validate the results reported in
      this study.

PMID- 20673075
TI  - Staying Steady: a community-based exercise initiative for falls prevention.
AB  - Over the past decade falls in the older population have become a priority in
      government policy. There is good evidence to suggest that tailored exercise
      effectively reduces falls; however, much of this evidence takes the form of
      randomized controlled trials that do not reflect the diversity of clinical
      practice. In response to emerging evidence, a community falls prevention program,
      called Staying Steady, was developed targeting older people at risk of falls. The
      program was evaluated using a mixed methods approach to capture both the personal
      experiences of the five participants, and any measurable clinical outcomes. The
      narrative accounts, supported by the measurable clinical outcomes, indicated that
      it was possible to replicate the results of large trials at a local level. The
      qualitative aspect of the evaluation enabled detailed consideration of other
      issues important to falls prevention programs. A social cognitive model was used
      to explain the reasons why participants either did, or did not, adhere to the
      program. The acceptability of the program to the participants was also explored
      in detail. Recommendations have been made to develop the Staying Steady program
      for future service users.

PMID- 20673076
TI  - Effect of pulsed ultrasound on chronic rhinosinusitis: a case report.
AB  - This case report demonstrates that pulsed ultrasound (US), when used for a total
      of 20 treatment sessions, provided symptom relief to a patient with chronic
      rhinosinusitis (CRS). A 16-year-old boy with a 12-month history of rhinosinusitis
      and candidate for sinus surgery was referred for ultrasound therapy. He presented
      with facial pain/pressure, nasal obstruction, and postnasal drip (total sinusitis
      score=7). On computed tomographic (CT) scanning, the total opacification of the
      right maxillary sinus was observed. The ostiomeatal complex was occluded (total
      CT score=6). Pulsed ultrasound was administered three times a week, every other
      day. After 10 treatment sessions, his symptoms were resolved with exception of
      nasal obstruction being mild (total sinusitis score=2). On CT scan, right
      maxillary sinus showed partial improvement (total CT score=2). After additional
      10 treatments, the nasal obstruction was resolved, and follow-up CT scan of his
      sinuses showed that right maxillary sinus was clear and normal. At 6-month follow
      up, the positive effects were maintained and the patient reported no recurrence
      of symptoms. Twenty sessions of pulsed ultrasound therapy eradicated the CRS and
      resolved the symptoms.

PMID- 20673077
TI  - The classical and a modified Boston brace: description and results.
AB  - Idiopathic scoliosis (IS) is characterized by the lateral deviation of the spine
      and constitutes a three-dimensional distortion that leads to geometric and
      morphological lesions in the spine and thoracic cage. The most widespread method
      of conservative management is to use spinal orthoses or body braces. These are
      usually recommended in patients with skeletal immaturity with a Risser sign 2 or
      less and with curves ranging from 25 degrees  to 45 degrees . Of these, perhaps
      one of the most popular in recent years is the Boston Brace. It was developed in
      the early 1970s, and its design is based on symmetry, consisting of extensions
      and pads, with each of them exerting corrective forces and has a specific role
      depending on the type of scoliosis. It is important that the treatment group, the
      patient, and the family environment should work as a team consistently and be
      well trained to achieve the best result. Various studies published in
      international literature have observed beneficial effects from the use of the
      Boston system. Nevertheless, there are still issues that need further
      investigation regarding its effectiveness depending on the type of curves, the
      duration of application, the gender, and BMI of patients to whom it is applied.
      However, without question, if all these factors are taken into account and with
      the compliance of the therapy group with the instructions, the main goal can be
      achieved, which is the stability of the spine, and the ultimate result of
      clinical-radiological and aesthetic improvement, which is directly linked to the
      psychological satisfaction of the patient.

PMID- 20673078
TI  - Improving gross motor function and postural control with hippotherapy in children
      with Down syndrome: case reports.
AB  - The purpose of this case report is to describe the impact of an 11-week
      hippotherapy program on the gross motor functions of two children (respectively
      28 and 37 months old) diagnosed with Down syndrome. Hippotherapy is a strategy
      that uses the horse's motion to stimulate and enhance muscle contraction and
      postural control. The children were assessed by the Gross Motor Function Measure
      (GMFM) and accelerometry. The results indicate that both children improved on
      many dimensions of the GMFM. Power spectral analysis of the acceleration signals
      showed improvement in postural control of either the head or trunk, because the
      children adopted two different adaptative strategies to perturbation induced by
      the moving horse.

PMID- 20673079
TI  - Between-session changes predict overall perception of improvement but not
      functional improvement in patients with shoulder impingement syndrome seen for
      physical therapy: an observational study.
AB  - Do between-session changes in global rating of change (GRoC) predict change in
      GRoC and self-report of function at discharge in patients with shoulder
      impingement that initially improve in early sessions of treatment (GRoC>5)? Is
      there a difference between individuals who initially respond to treatment
      (GRoC>5) compared to those that do not (GRoC<5) for self-report of function? This
      longitudinal, observational study had 55 patients seen for a formal physical
      therapy program after a medical diagnosis of shoulder impingement. Physical
      therapy used a standardized protocol. The American Shoulder and Elbow Surgeons
      Subjective Shoulder Scale (ASES) and self-report of improvement of condition
      using the GRoC were measured. We found no significant correlation between the
      first visits between-sessions changes of the GRoC and the change score of the
      ASES (r=0.13; p=0.39) in patients with shoulder impingement that initially
      improve in early sessions of treatment (GRoC>5). There was a moderate correlation
      between the first visits between-session changes of the GRoC and the final
      reported GRoC (r=0.48; p<0.01) for the patients who responded to treatment. There
      was no difference in ASES change scores between those who initially respond to
      treatment (N=10) and those who do not (N=34). ASES mean change scores were 21.5
      for the responders and 14.3 for the non-responders. These findings suggest that a
      GRoC of 5 or greater is related to a perceived change in one's condition upon
      termination of formal physical therapy but is not related to actual improvement
      in one's self-report of function. This finding suggests that the construct of the
      GRoC may not be related to the constructs of the ASES, or between-session changes
      are not prognostic in patients with shoulder impingement and should not solely
      dictate treatment decision making.

PMID- 20673080
TI  - Stigma and sexual health risk in HIV-positive African American young men who have
      sex with men.
AB  - Understanding the multiple forms of stigma experienced by young HIV-positive
      African American men who have sex with men and how they relate to sexual risk
      behaviors is essential to design effective HIV prevention programs. This study of
      40 African American young MSM found that 90% of those surveyed experienced sexual
      minority stigma, 88% experienced HIV stigma, and 78% experienced dual stigma.
      Sexual minority stigma was characterized by experiences of social avoidance, and
      HIV stigma, by shame. Individuals with high HIV stigma were significantly more
      likely to engage in unprotected sex while high or intoxicated. Associations
      between stigma and sexual practices were examined; youth endorsing higher levels
      of sexual minority stigma engaged in less insertive anal intercourse. Individuals
      endorsing more HIV stigma reported more receptive anal intercourse. These
      findings support the development of stigma-informed secondary prevention
      interventions for African American HIV-positive young MSM.

PMID- 20673081
TI  - The languages of healing: linked by a common thread.
AB  - Though separated by different millennia, languages, levels of scientific
      advancement, and views of human physiology, both prehistoric and modern cultures
      have expressed concepts of evaluating and treating human illness that have
      remarkable overlap with those of Traditional Chinese Medicine (TCM). These
      similarities suggest these healing traditions likely are expressing a common,
      fundamental aspect of human anatomy and/or physiology. Prehistoric, ancient
      Egyptian, TCM, Mayan, myofascial pain, and myofascial meridian concepts of health
      and healing are discussed. Anatomical, clinical, and physiologic evidence is
      presented that suggests neuroanatomy is likely the common thread that unites
      these ancient and modern healing concepts. These findings should lead to an
      increased understanding of the anatomical and physiologic substrates of the
      beneficial clinical effects of acupuncture in treating pain and visceral
      disorders. This, in turn, should lead to novel, safer treatment techniques that
      combine modern technologies with ancient clinical acumen.

PMID- 20673083
TI  - Evaluation of isoeugenol for anesthesia in koi carp (Cyprinus carpio).
AB  - OBJECTIVE: To evaluate isoeugenol as an anesthetic agent in koi carp. ANIMALS:
      216 juvenile koi carp (Cyprinus carpio). PROCEDURES: Fish were randomly allocated
      to 9 groups of 24, and each group was randomly exposed to isoeugenol
      concentrations ranging from 0 to 500 mg/L. General activity, excitement, fin and
      gill color changes, opercular movement rate, loss of equilibrium, muscle tone,
      jaw tone, and handleability were assessed. Five fish from the control (0 mg/L),
      200 mg/L, and 500 mg/L groups were randomly selected prior to anesthetic recovery
      and again 24 hours after recovery for euthanasia, gross necropsy, and histologic
      assessment of gills, internal viscera, and skeletal muscles. RESULTS: Mean +/- SD
      interval to achieve stage 2 anesthesia with isoeugenol ranged from 22.4 +/- 6.2
      minutes at 20 mg/L to 0.25 +/- 0.4 minutes at 500 mg/L, whereas the mean interval
      to stage 3 anesthesia ranged from 28.1 +/- 3.9 minutes at 20 mg/L to 0.33 +/-
      0.48 minutes at 500 mg/L. With the exception of the 500 mg/L group, opercular
      movements were maintained throughout. Death was observed only in the 500 mg/L
      group, in which 50% of the fish either failed to recover or died within 24 hours
      after anesthetic exposure. There were no pathological differences between fish
      exposed to isoeugenol at 0 or 500 mg/L. CONCLUSIONS AND CLINICAL RELEVANCE:
      Isoeugenol appeared to have a wide margin of safety with predictable dose-related
      effects. Concentrations of 40 to 80 mg/L induced anesthesia within 4 to 11
      minutes and were considerably less than the concentration associated with fish
      death.

PMID- 20673084
TI  - Effects of positive end-expiratory pressure on anesthesia-induced atelectasis and
      gas exchange in anesthetized and mechanically ventilated sheep.
AB  - OBJECTIVE: To evaluate the effects of 10 cm H(2)O of positive end-expiratory
      pressure (PEEP) on lung aeration and gas exchange in mechanically ventilated
      sheep during general anesthesia induced and maintained with propofol. ANIMALS: 10
      healthy adult Bergamasca sheep. PROCEDURES: Sheep were sedated with diazepam (0.4
      mg/kg, IV). Anesthesia was induced with propofol (5 mg/kg, IV) and maintained
      with propofol via constant rate infusion (0.4 mg/kg/min). Muscular paralysis was
      induced by administration of vecuronium (25 microg/kg, bolus IV) to facilitate
      mechanical ventilation. After intubation, sheep were positioned in right lateral
      recumbency and mechanically ventilated with pure oxygen and zero end-expiratory
      pressure (ZEEP). After 60 minutes, 10 cm H(2)O of PEEP was applied for 20
      minutes. Spiral computed tomography of the thorax was performed, and data were
      recorded for hemodynamic and gas exchange variables and indicators of respiratory
      mechanics after 15 (T(15)), 30 (T(30)), and 60 (T(60)) minutes of ZEEP and after
      20 minutes of PEEP (T(PEEP)). Computed tomography images were analyzed to
      determine the extent of atelectasis before and after PEEP application. RESULTS:
      At T(PEEP), the volume of poorly aerated and atelectatic compartments was
      significantly smaller than at T(15), T(30), and T(60), which indicated that there
      was PEEP-induced alveolar recruitment and clearance of anesthesia-induced
      atelectasis. Arterial oxygenation and static respiratory system compliance were
      significantly improved by use of PEEP. CONCLUSIONS AND CLINICAL RELEVANCE:
      Pulmonary atelectasis can develop in anesthetized and mechanically ventilated
      sheep breathing pure oxygen; application of 10 cm H(2)O of PEEP significantly
      improved lung aeration and gas exchange.

PMID- 20673085
TI  - Evaluation of chondrocyte death in canine osteochondral explants exposed to a
      0.5% solution of bupivacaine.
AB  - OBJECTIVE: To evaluate chondrocyte death in canine articular cartilage exposed in
      vitro to bupivacaine with and without methylparaben and to compare viability for
      cartilage with intact or mechanically debrided surfaces. SAMPLE POPULATION: Both
      glenohumeral joints from 10 adult canine cadavers. PROCEDURES: 10 osteochondral
      cores were harvested from each of the 20 humeral heads; synovium and 1 core from
      each joint were examined to verify joint health, and the other 9 cores were
      exposed to canine chondrocyte culture medium (CCCM), a 0.5% solution of
      bupivacaine, or 0.5% solution of bupivacaine with methylparaben for 5, 15, or 30
      minutes. RESULTS: For the superficial zone of surface-intact chondrocytes,
      bupivacaine with methylparaben caused a significantly higher percentage of
      chondrocyte death at 5 minutes (47.7%) than did bupivacaine (23.6%) or CCCM
      (25.4%). Bupivacaine (53.8%) and bupivacaine with methylparaben (62.5%) caused a
      significantly higher percentage of chondrocyte death at 30 minutes than did CCCM
      (20.0%). For the superficial zone of chondrocytes with debrided surfaces,
      bupivacaine with methylparaben caused a significantly higher percentage of
      chondrocyte death at 30 minutes (59%) than it did at 5 minutes (37.7%).
      Bupivacaine with methylparaben caused a significantly higher percentage of
      chondrocyte death at 30 minutes (59.0%) than did CCCM (28.9%). For middle and
      deep zones of chondrocytes, treatment solution and surface debridement had
      minimal effects on percentage of chondrocyte death. CONCLUSIONS AND CLINICAL
      RELEVANCE: Bupivacaine and bupivacaine with methylparaben were cytotoxic to
      canine articular chondrocytes in vitro. Intra-articular administration of
      bupivacaine is not recommended for clinical use until additional studies are
      conducted.

PMID- 20673086
TI  - Evaluation of radiographic and genetic aspects of hereditary subluxation of the
      radial head in Bouviers des Flandres.
AB  - OBJECTIVE: To study radiographic and genetic aspects of hereditary radial head
      subluxation in Bouviers des Flandres. ANIMALS: 26 related Bouviers des Flandres
      affected with bilateral subluxation of the radial head, 10 unaffected related
      dogs, and 29 unrelated Bouviers des Flandres with diagnoses of nonskeletal
      diseases. PROCEDURES: All dogs were radiographically studied, and their DNA was
      analyzed with a genome-wide screen of 1,536 single nucleotide polymorphisms. In
      addition, karyotyping was performed in an unaffected dam and its affected
      offspring. RESULTS: Both forelimbs of affected dogs were disproportionately short
      with caudolateral subluxation or luxation of the radial head. Angulation of the
      radial axis at the mid-diaphysis ranged from 9.3 degrees to 30.3 degrees (mean +/
      SD, 14.9 +/- 6.1 degrees ), with an estimated age of onset from 0 to 4 months.
      Poorly defined medial coronoid processes and osteoarthritis of the elbow joint,
      cranial bowing of the olecranon, and disturbed growth in length of the ulna with
      sharply demarcated spurs were noticed on radiographs of affected dogs.
      Genealogical analysis indicated that most affected dogs were closely related, but
      the mode of inheritance was not clear. The DNA analysis found that 205 single
      nucleotide polymorphisms were monomorphic in the affected dogs. Conventional
      chromosome staining revealed no numerical chromosomal aberration. CONCLUSIONS AND
      CLINICAL RELEVANCE: Congenital radial head luxation and subluxation in the
      studied Bouviers des Flandres were characterized by angulation of the radial axis
      leading to caudolateral subluxation of the radial head and insufficient growth of
      the distal portion of the ulna together with cranial bowing of the olecranon.

PMID- 20673087
TI  - Evaluation of the influence of age on pulmonary arterial pressure by use of right
      ventricular catheterization, pulsed-wave Doppler echocardiography, and pulsed
      wave tissue Doppler imaging in healthy Beagles.
AB  - OBJECTIVE: To assess the influence of age on pulmonary hemodynamics and
      hemorheological properties in healthy dogs. ANIMALS: 14 healthy Beagles.
      PROCEDURES: Dogs were placed in 2 age groups as follows: young dogs (<or= 5 years
      old; n = 8) and old dogs (>or= 8 years old; 6). Hematologic characteristics,
      plasma total protein and fibrinogen concentrations, and blood viscosity were
      measured. Systolic time intervals of pulmonary blood flow were recorded by pulsed
      wave Doppler echocardiography. Early (E') and late (A') diastolic myocardial
      velocities, isovolumic contraction velocity, and systolic myocardial velocity of
      the free tricuspid annulus were recorded by pulsed-wave tissue Doppler imaging
      (TDI). Dogs were anesthetized and pulmonary arterial pressures (PAP) and cardiac
      output were recorded with a pediatric thermodilution Swan-Ganz catheter. RESULTS:
      Hemorheological measurements were not different between the 2 groups. Systolic,
      mean, and diastolic PAP were higher in old dogs, compared with values in young
      dogs; this difference was attributed to a high pulmonary vascular resistance and
      low arterial compliance in old dogs. Systolic time intervals of pulmonary blood
      flow stayed unchanged. The A' wave of the free tricuspid annulus was increased in
      old, compared with that young dogs, and the E':A' ratio was decreased. Pulmonary
      vascular resistance was inversely correlated with compliance. CONCLUSIONS AND
      CLINICAL RELEVANCE: The age of dogs should be taken into account when
      interpreting pulmonary hemodynamic results and TDI variables of right ventricular
      diastolic function.

PMID- 20673088
TI  - Assessment of the relationship between body weight and gastrointestinal transit
      times measured by use of a wireless motility capsule system in dogs.
AB  - OBJECTIVE: To assess the relationship between body weight and gastrointestinal
      transit times measured by use of a wireless motility capsule (WMC) system in
      healthy dogs. ANIMALS: 31 healthy adult dogs that weighed between 19.6 and 81.2
      kg. PROCEDURES: Food was withheld overnight. The following morning, a WMC was
      orally administered to each dog, and each dog was then fed a test meal that
      provided a fourth of the daily energy requirements. A vest was fitted on each dog
      to hold a receiver that collected and stored data from the WMC. Measurements were
      obtained with each dog in its home environment. Regression analysis was used to
      assess the relationship between body weight and gastrointestinal transit times.
      RESULTS: Gastric emptying time (GET) ranged from 405 to 897 minutes, small bowel
      transit time (SBTT) ranged from 96 to 224 minutes, large bowel transit time
      (LBTT) ranged from 427 to 2,573 minutes, and total transit time (TTT) ranged from
      1,294 to 3,443 minutes. There was no positive relationship between body weight
      and gastrointestinal transit times. A nonlinear inverse relationship between body
      weight and GET and between body weight and SBTT best fit the data. The LBTT could
      not be explained by this model and likely influenced the poor fit for the TTT.
      CONCLUSIONS AND CLINICAL RELEVANCE: A positive relationship did not exist between
      body weight and gastrointestinal transit times. Dogs with the lowest body weight
      of the cohort appeared to have longer gastric and small intestinal transit times
      than did large- and giant-breed dogs.

PMID- 20673089
TI  - Variability associated with repeated measurements of gastrointestinal tract
      motility in dogs obtained by use of a wireless motility capsule system and
      scintigraphy.
AB  - OBJECTIVE: To compare repeatability of measurements of gastrointestinal tract
      motility in healthy dogs obtained by use of a wireless motility capsule (WMC) and
      scintigraphy. ANIMALS: 6 healthy adult dogs (mean +/- SD body weight, 21.5 +/-
      1.8 kg). PROCEDURES: A radiolabeled test meal was offered immediately after oral
      administration of a WMC. Serial static scintigraphic abdominal images were
      acquired for 270 minutes. A dedicated remote receiver was used for data
      collection from the WMC until the WMC was expelled in the feces. Each dog was
      evaluated 3 times at intervals of 1 to 2 weeks. RESULTS: Mean gastric emptying
      half-time measured by use of scintigraphy (T(1/2)-GES) for each dog ranged from
      99.9 to 181.2 minutes. Mean gastric emptying time (GET) measured by use of the
      WMC (GET-WMC) in each dog ranged from 385.3 to 669.7 minutes. Mean coefficient of
      variation was 11.8% for T(1/2)-GES and 7.8% for GET-WMC. The intraclass
      correlation coefficient was 69% for T(1/2)-GES and 71% for GET-WMC. Results for a
      nested analysis of covariance suggested that both methods were comparable for the
      evaluation of gastric emptying. CONCLUSIONS AND CLINICAL RELEVANCE: Scintigraphy
      and a WMC system had similar variation for assessment of gastric emptying.
      Moderate intraindividual variability was detected for both methods and must be
      considered when interpreting test results for individual dogs. Repeatability of
      measurements obtained by use of the WMC was equivalent to that obtained by use of
      scintigraphy. The WMC system offers a nonradioactive, user-friendly method for
      assessment of gastric emptying in dogs.

PMID- 20673090
TI  - Validation of a urine test and characterization of the putative genetic mutation
      for hyperuricosuria in Bulldogs and Black Russian Terriers.
AB  - OBJECTIVE: To determine whether hyperuricosuria was a predisposing factor for
      urate urolithiasis in Bulldogs and Black Russian Terriers (BRTs) and to estimate
      the allele frequency of the Cys181Phe genetic mutation in urate transporter
      SLC2A9 in these breeds. ANIMALS: 192 Bulldogs, 101 BRTs, 10 Dalmatians, and 9
      dogs of other breeds. PROCEDURES: Uric acid (UA) and creatinine (Cr)
      concentrations were quantified in urine samples collected from all dogs via
      midstream catch during natural voiding. Buccal swab or blood samples were also
      obtained, and DNA was extracted and used to genotype SLC2A9 sequence variants by
      use of pyrosequencing assays. A urine test for hyperuricosuria was validated in
      adult dogs by comparing urinary UA:Cr ratios between known hyperuricosuric and
      nonhyperuricosuric dogs. RESULTS: Significantly higher UA:Cr ratios were found in
      some Bulldogs and BRTs, compared with ratios in other dogs from these breeds.
      These dogs were also homozygous for the SLC2A9 Cys181Phe mutation. The allele
      frequency of the Cys181Phe mutation was 0.16 in Bulldogs and 0.51 in BRTs. On the
      basis of these allele frequencies, 3% of the Bulldog population and 27% of the
      BRT population were estimated to be hyperuricosuric. CONCLUSIONS AND CLINICAL
      RELEVANCE: Results suggested the genetic mutation associated with
      hyperuricosuria, first identified in Dalmatians, also appears to cause
      hyperuricosuria in Bulldogs and BRTs, indicating that similar management
      strategies for urate urolithiasis can be used in these breeds. The allele
      frequency of the mutation was high in both breeds, and DNA testing can be used to
      select against the mutation.

PMID- 20673091
TI  - Expression of inflammation-associated genes in circulating leukocytes collected
      from horses with gastrointestinal tract disease.
AB  - OBJECTIVE: To investigate whether expression of inflammation-associated genes in
      leukocytes from horses with gastrointestinal tract (GIT) diseases correlated with
      the type of disease and outcome. ANIMALS: 10 healthy horses and 50 horses with
      GIT disease. PROCEDURES: A blood sample was collected from each healthy horse or
      horse with GIT disease (during admission to the hospital). Leukocytes were
      isolated, diluted to a standard concentration, and frozen until RNA extraction.
      Expression of 14 genes associated with inflammation was quantified by use of a
      real-time quantitative reverse transcription PCR assay. Results were grouped by
      GIT disease type and disease outcome for comparison. RESULTS: Horses with GIT
      disease had colic of unknown etiology (n = 8 horses), GIT inflammation or
      strangulation (19), or nonstrangulating GIT obstruction (23). Among the 45 horses
      receiving treatment, 38 were discharged from the hospital, and 7 died or were
      euthanized. Compared with healthy horses, horses with colic of unknown etiology
      had similar gene expression. Significant differences in expression of the
      interleukin-8, leukocyte-selectin molecule, matrix metalloproteinase-9, platelet
      selectin molecule, mitochondrial superoxide dismutase, Toll-like receptor 4, and
      tumor necrosis factor-A genes were detected between healthy horses and horses
      with GIT disease. Significant differences in expression of the interleukin-1
      receptor antagonist, interleukin-8, leukocyte-selectin molecule, matrix
      metalloproteinase-9, platelet-selectin molecule, mitochondrial superoxide
      dismutase, Toll-like receptor 4, and tumor necrosis factor-A genes were detected
      among healthy horses and horses grouped by disease outcome. CONCLUSIONS AND
      CLINICAL RELEVANCE: Inflammatory gene expression in leukocytes of horses with GIT
      disease appeared to be related to disease pathogenesis and prognosis.

PMID- 20673092
TI  - Detection of pathogenic elephant endotheliotropic herpesvirus in routine trunk
      washes from healthy adult Asian elephants (Elephas maximus) by use of a real-time
      quantitative polymerase chain reaction assay.
AB  - OBJECTIVE: To investigate the pathogenesis and transmission of elephant
      endotheliotropic herpesvirus (EEHV1) by analyzing various elephant fluid samples
      with a novel EEHV1-specific real-time PCR assay. ANIMALS: 5 apparently healthy
      captive Asian elephants (Elephas maximus) from the same herd. PROCEDURES: A real
      time PCR assay was developed that specifically detects EEHV1. The assay was used
      to evaluate paired whole blood and trunk-wash samples obtained from the 5
      elephants during a 15-week period. Deoxyribonucleic acid sequencing and viral
      gene subtyping analysis were performed on trunk-wash DNA preparations that had
      positive results for EEHV1. Viral gene subtypes were compared with those
      associated with past fatal cases of herpesvirus-associated disease within the
      herd. RESULTS: The PCR assay detected viral DNA to a level of 1,200 copies/mL of
      whole blood. It was used to detect EEHV1 in trunk secretions of 3 of the 5
      elephants surveyed during the 15-week period. Viral gene subtyping analysis
      identified 2 distinct elephant herpesviruses, 1 of which was identical to the
      virus associated with a previous fatal case of herpesvirus-associated disease
      within the herd. CONCLUSIONS AND CLINICAL RELEVANCE: EEHV1 was shed in the trunk
      secretions of healthy Asian elephants. Trunk secretions may provide a mode of
      transmission for this virus. Results of this study may be useful for the
      diagnosis, treatment, and management of EEHV1-associated disease and the overall
      management of captive elephant populations.

PMID- 20673093
TI  - Evaluation of body composition and cartilage biomarkers in large-breed dogs fed
      two foods designed for growth.
AB  - OBJECTIVE: To evaluate cartilage and bone biomarkers and body composition in
      growing large-breed dogs consuming a diet designed for growth. ANIMALS: 43 large
      breed 2 month-old-puppies. PROCEDURES: Dogs were randomly assigned to receive 1
      of 2 foods until 18 months of age. Dogs were evaluated at 2, 5, 12, and 18 months
      of age via dual energy x-ray absorptiometry (DEXA), CBC, serum biochemical
      profile, and concentrations or activities of taurine, vitamin E, fatty acids,
      glutathione peroxidase, C-propeptide of type II collagen (CPII), cartilage
      oligomeric matrix protein (COMP), carboxy-terminal cross-linked fragment of type
      II collagen (CTXII), bone specific alkaline phosphatase (BAP), osteocalcin,
      ghrelin, and growth hormone. RESULTS: Blood components largely reflected the
      composition of the foods. Dogs fed the food with a higher concentration of
      protein, calcium, n-3 fatty acids, and antioxidants had a lower percentage of
      body fat and greater percentage of lean body mass at 5, 12, and 18 months of age,
      and higher CPII:CTXII ratio and lower COMP at 18 months of age. The BAP activity,
      osteocalcin concentration, and CTXII concentration declined with age, whereas
      COMP concentration and CPII concentration were similar at all time points for
      both foods. CONCLUSIONS AND CLINICAL RELEVANCE: The BAP activity, osteocalcin
      concentration, and CTXII concentration were greater during growth than at 18
      months of age. The food that was proportionately higher in protein, calcium, n-3
      fatty acids, and antioxidants increased lean body mass and may have positively
      affected cartilage turnover as maturity was attained. Whether the rate of
      cartilage turnover during growth affects development of orthopedic disease or
      arthritis in adulthood has yet to be determined.

PMID- 20673094
TI  - Serum cortisol concentration and force plate analysis in the assessment of pain
      associated with sodium urate-induced acute synovitis in dogs.
AB  - OBJECTIVE: To determine the relationship between serum cortisol concentration and
      pain severity as measured by force platform gait analysis in dogs with
      experimentally induced synovitis of the stifle joint. ANIMALS: 10 healthy hound
      type dogs. PROCEDURES: Dogs underwent 2 study phases. In the first phase, serum
      cortisol concentration, systolic arterial blood pressure, heart rate, and gait
      data were obtained at 0 (first sample), 2.5, 5, 7.5, and 10 hours. In the second
      phase, the same data were gathered immediately before (0 hours) and 2.5, 5, 7.5,
      and 10 hours after induction of acute urate synovitis in the left stifle joint.
      Data were statistically evaluated to compare changes in variable values over time
      and to determine the accuracy of serum cortisol measurements for diagnosis of
      acute orthopedic pain. RESULTS: Following induction of synovitis, ground reaction
      forces were significantly decreased relative to preinduction values at 2.5, 5.0,
      7.5, and 10.0 hours and serum cortisol concentration was significantly increased
      at 2.5 hours. A cortisol concentration of >or= 1.6 microg/dL indicated pain with
      a 91% sensitivity and 35% specificity. CONCLUSIONS AND CLINICAL RELEVANCE: In
      this model, cortisol concentration may be useful for diagnosing pain in dogs.
      Although, with a cutoff of >or= 1.6 microg/dL, pain would be detected in most
      dogs with pain, some pain-free dogs would also be identified as having pain.
      Conversely, dogs with a serum cortisol of < 1.6 microg/dL would be unlikely to
      have pain. Validation of this diagnostic test in a large, heterogeneous group of
      clinical patients is necessary.

PMID- 20673095
TI  - Use of serum biomarkers to predict the development and severity of
      osteochondrosis lesions in the distal portion of the femur in pigs.
AB  - OBJECTIVE: To evaluate the use of serum biomarkers of cartilage and bone
      metabolism to predict the occurrence and severity of osteochondrosis (OC) lesions
      in the distal portion of the femur in growing swine. ANIMALS: 71 gilts.
      PROCEDURES: At an abattoir, serum samples for analysis of 10 biomarkers
      indicative of cartilage and bone metabolism were obtained prior to processing of
      the pigs. The distal portion of each pig's left femur was directly examined and
      cut into longitudinal sections to evaluate the number and severity of
      abnormalities on the external surface, articular cartilage, and growth plate.
      Each specimen was categorized as with (n = 56) or without (15) OC, and an overall
      OC severity score was assigned to affected pigs. Logistic and linear regression
      analyses were performed to predict odds of OC on the basis of biomarker
      concentrations and predict the severity of OC values in affected pigs,
      respectively. RESULTS: Compared with values in unaffected pigs, serum
      concentrations of C-propeptide of type II collagen (CPII) and cartilage
      oligomeric matrix protein were significantly increased and concentrations of
      carboxy-terminal telopeptide of type II collagen 3/4-length fragment (C2C) and
      pyridinoline cross-links were significantly decreased in affected pigs. A 2-fold
      increase in CPII concentration increased the odds of pigs having OC by a factor
      of 97 (95% confidence interval, 6 to infinity). Changes in serum C2C
      concentration accounted for 49% of the variation in overall OC severity score.
      CONCLUSIONS AND CLINICAL RELEVANCE: Assessment of serum biomarker concentrations
      may be useful in the diagnosis of OC and aid in reduction of lameness in swine
      herds.

PMID- 20673096
TI  - Effects of antifungal drugs and delivery vehicles on morphology and proliferation
      of equine corneal keratocytes in vitro.
AB  - OBJECTIVE: To evaluate the effects of topical antifungal drugs and delivery
      vehicles on the morphology and proliferation rate of cultured equine keratocytes.
      STUDY POPULATION: 16 corneas obtained from 8 apparently ophthalmologically normal
      horses < 0.5 hours after euthanasia for reasons unrelated to the study.
      PROCEDURES: Primary cultures of equine keratocytes were obtained from corneal
      stroma and were exposed to several concentrations of 3 commonly used, topically
      applied antifungals: natamycin, itraconazole, and miconazole. In addition,
      effects of drug delivery vehicles DMSO, benzalkonium chloride, and
      carboxymethylcellulose and a combination vehicle composed of polyethylene glycol,
      methylparaben, and propylparaben were also evaluated. Morphological changes and
      cellular proliferation were assessed 24, 48, and 72 hours after application.
      RESULTS: At the highest concentrations tested, all antifungals caused marked
      cellular morphological changes and inhibited proliferation. At low
      concentrations, natamycin and miconazole induced rounding, shrinking, and
      detaching of the cells with inhibition of cellular proliferation. Natamycin
      caused the most severe cellular changes. Itraconazole, at the low concentrations,
      caused minimal morphological changes and had a minimal effect on proliferation.
      All vehicles tested had significantly less effects on cellular morphology and
      proliferation when compared with the antifungals, except for the combination
      vehicle, which caused severe morphological changes and inhibited proliferation,
      even at low concentrations. The DMSO had minimal effects on cellular morphology
      and proliferation, even at high concentrations. CONCLUSIONS AND CLINICAL
      RELEVANCE: Itraconazole had significantly less cytotoxic effects on equine
      keratocytes in culture than did natamycin or miconazole. Natamycin had severe
      cytotoxic effects in vitro.

PMID- 20673097
TI  - Use of an in vitro biotinylation technique for determination of posttransfusion
      survival of fresh and stored autologous red blood cells in Thoroughbreds.
AB  - OBJECTIVE: To evaluate N-hydroxysuccinimide (NHS)-biotin labeling of equine RBCs
      and determine posttransfusion survival of autologous equine RBCs stored in
      citrate phosphate dextrose adenine-1 (CPDA-1) for 0, 1, 14, and 28 days. ANIMALS:
      13 healthy adult Thoroughbreds. PROCEDURES: Serial dilutions of biotin and
      streptavidin-phycoerythrin (PE) were evaluated in vitro in blood collected from 3
      horses. One horse was used to determine RBC distribution and recovery. Twelve
      horses were allocated to 4 groups for in vivo experiments in which blood was
      collected into CPDA-1. Blood was labeled with biotin and reinfused or stored at 4
      degrees C for 1, 14, or 28 days prior to labeling with NHS-biotin and reinfusion.
      Posttransfusion blood samples were collected 15 minutes and 1, 2, 3, 5, 7, 14,
      21, 28, and 35 days after reinfusion. Biotin-labeled RBCs were detected via flow
      cytometry by use of streptavidin-PE. Posttransfusion lifespan of RBCs and RBC
      half-life were determined. RESULTS: Optimal biotin concentration was 0.04 pg of
      biotin/RBC, and the optimal streptavidin-PE ratio was 1.2 microg of streptavidin
      PE/1 x 10(6) RBCs. Posttransfusion lifespan of autologous RBCs was 99, 89, 66,
      and 59 days after storage for 0, 1, 14, and 28 days, respectively. Storage did
      not result in significant alterations in RBC lifespan. Mean posttransfusion RBC
      half-life was 50, 45, 33, and 29 days for 0, 1, 14, and 28 days of storage,
      respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Biotin can be used to label
      equine RBCs for RBC survival studies. Posttransfusion survival of equine
      autologous RBCs was greater than previously reported.

PMID- 20673098
TI  - Effects of acute dilutional hyponatremia on acid-base changes and electrolyte
      concentrations in rats with bilateral renal pedicle ligation.
AB  - OBJECTIVE: To describe the effects of increasing the extracellular fluid (ECF)
      volume by approximately 20% on acid-base changes and electrolyte concentrations
      in anesthetized rats. ANIMALS: 18 adult male Sprague-Dawley rats. PROCEDURES:
      Rats were assigned to a control group (n = 6 rats) and a treatment group (12).
      All rats were anesthetized, and instrumentation and bilateral renal pedicle
      ligation were performed. The treatment group was infused IV with sterile water
      throughout a 30-minute period. Acid-base variables and concentrations of
      electrolytes, lactate, albumin, phosphorus, and hemoglobin were measured before
      (baseline) and 30 and 60 minutes after onset of infusion. Anion gap, strong ion
      difference, strong ion gap, and contributions of sodium, chloride, albumin,
      phosphorus, and lactate concentrations to base excess were calculated at each
      time point. RESULTS: Infusion of sterile water led to an increase in ECF volume
      of approximately 18%. This had no effect on acid-base balance, compared with that
      in control rats. Infusion of sterile water caused a significant decrease in
      sodium, chloride, ionized calcium, lactate, and albumin concentrations, compared
      with concentrations in the control group. Anion gap and calculated effects of
      sodium, chloride, albumin, and lactate concentrations on base excess at 60
      minutes differed significantly between infused and control rats. CONCLUSIONS AND
      CLINICAL RELEVANCE: Infusion of sterile water did not cause clinically relevant
      dilutional acidosis. The acidotic impact of water administration was offset by
      generation of new bicarbonate via carbonic acid equilibration and intracellular
      buffering in combination with the alkalotic effects of decreases in albumin,
      phosphorus, and lactate concentrations.

PMID- 20673099
TI  - In vitro comparison of two centrally threaded, positive-profile transfixation pin
      designs for use in third metacarpal bones in horses.
AB  - OBJECTIVE: To compare heat generation during insertion, pullout strength, and
      associated microdamage between a self-tapping positive profile transfixation pin
      (STTP) and nontapping positive profile transfixation pin (NTTP). SAMPLE
      POPULATION: 30 pairs of third metacarpal bones (MC3s) from adult equine cadavers.
      PROCEDURES: One MC3 of each pair was assigned to the STTP group; the other was
      assigned to the NTTP group. The assigned pin was inserted into the diaphysis in a
      lateral to medial direction. Bone temperature increase during pilot-hole drilling
      and pin insertion was recorded at 1 mm from the final thread position with wire
      thermocouples at cis and trans cortices. Resistance to axial extraction before
      and after cyclic loading was measured in a material testing device, and
      microstructural damage caused by transfixation pin insertion was assessed with
      scanning electron microscopy. RESULTS: The STTP group developed a significant
      increase in bone temperature, compared with the NTTP group. No significant
      difference was found between the mean maximal pullout strength of the STTP and
      the NTTP in both non-cyclic-loaded and cyclic-loaded groups. Microdamage to the
      bone-pin interface was lower when the STTP versus the NTTP was used, but more
      bone debris was apparent after inserting the STTP. CONCLUSION AND CLINICAL
      RELEVANCE: Because of the significant increase in temperature generation and
      debris accumulation despite similar pullout strengths and lesser microfracture
      formation, the STTP likely poses a higher risk of bone necrosis and potential
      loosening than the NTTP. This might be corrected by redesign of the tapping
      aspect of the STTP.

PMID- 20673100
TI  - Measurement of urinary cauxin in geriatric cats with variable plasma creatinine
      concentrations and proteinuria and evaluation of urine cauxin-to-creatinine
      concentration ratio as a predictor of developing azotemia.
AB  - OBJECTIVE: To evaluate urine cauxin immunoreactivity in geriatric cats with
      variable plasma creatinine concentrations and proteinuria and to assess urinary
      cauxin-to-creatinine concentration ratio (UC/C) as a predictor of developing
      azotemia. ANIMALS: 188 client-owned geriatric (>or= 9 years of age) cats.
      PROCEDURES: A direct immunoassay was developed and validated for the
      quantification of urinary cauxin relative to a standard curve generated from a
      urine sample with high cauxin immunoreactivity. Relationships among UC/C, plasma
      creatinine concentration, and proteinuria were assessed. Nonazotemic cats were
      recruited and followed for 12 months. Urinary cauxin-to-creatinine concentration
      ratio was evaluated as a predictor of development of azotemia in these cats.
      RESULTS: No relationship was evident between UC/C and plasma creatinine
      concentration. A weak positive correlation was identified between UC/C and urine
      protein-to-creatinine concentration ratio (r = 0.212). At entry to the
      longitudinal study, those cats that later developed azotemia had a UC/C that was
      significantly higher than in those remaining nonazotemic after 12 months.
      CONCLUSIONS AND CLINICAL RELEVANCE: The UC/C did not vary with severity of
      azotemia but appeared contributory to the feline urinary proteome. High UC/C
      values were predictive of the geriatric cats in our study developing azotemia.
      However, it seems unlikely that UC/C will provide additional information about
      the measurement of urine protein-to-creatinine concentration ratio as a biomarker
      for the development of azotemia in cats.

PMID- 20673102
TI  - Finned animals increasingly seen as patients. Veterinarians in pet care,
      industry, education say interest and need expanding.

PMID- 20673103
TI  - Additional views on the costs of feral cat control.

PMID- 20673104
TI  - The ethics of influencing clients.

PMID- 20673105
TI  - What is your diagnosis? Wooden stick in the stomach.

PMID- 20673106
TI  - What is your diagnosis? Patellar tendon rupture.

PMID- 20673107
TI  - Pathology in practice. Diagnosis: Poliomyelitis with intraneuronal Negri bodies.

PMID- 20673108
TI  - Comparison of complete blood counts in samples obtained from healthy dogs and
      cats by use of standard and microsample blood collection tubes.
AB  - OBJECTIVE: To compare results of a CBC performed on blood samples obtained from
      healthy dogs and cats by use of standard and microsample collection tubes.
      DESIGN: Evaluation study. ANIMALS: 29 healthy client-owned animals (14 dogs and
      15 cats). PROCEDURES: A blood sample (3 mL) was collected from each animal; 2.5
      mL was transferred into a vacuum tube that contained sodium EDTA, and 0.5 mL was
      transferred into a microsample tube that contained sodium EDTA. Variables
      evaluated were total numbers of RBCs and WBCs, hemoglobin concentration, Hct,
      mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin
      concentration (MCHC), mean platelet volume, and plasma total protein
      concentration as well as neutrophil, lymphocyte, monocyte, eosinophil, basophil,
      and platelet counts. Results for the 2 types of tube in each species were
      compared by use of Pearson correlation coefficients, Passing-Bablok regression
      analysis, and Bland-Altman analysis. RESULTS: The Pearson correlation coefficient
      was low for basophil count in cats and moderate, high, or very high for all other
      variables. Constant and proportional biases were identified for MCHC in dogs by
      use of Passing-Bablok regression analysis, although the mean difference between
      types of blood collection tubes was small. No evidence of constant or
      proportional bias for any other variable was revealed by regression analysis or
      Bland-Altman analysis. CONCLUSIONS AND CLINICAL RELEVANCE: Samples obtained from
      healthy dogs and cats by use of microsample blood collection tubes provided
      clinically equivalent CBC results, compared with results for samples obtained by
      use of standard blood collection tubes, and minimized the total sample volume
      collected for diagnostic testing.

PMID- 20673109
TI  - Comparison of biochemical variables in plasma samples obtained from healthy dogs
      and cats by use of standard and microsample blood collection tubes.
AB  - OBJECTIVE: To compare results of biochemical analyses performed on plasma samples
      obtained from healthy dogs and cats by use of standard and microsample blood
      collection tubes. DESIGN: Evaluation study. ANIMALS: 29 healthy client-owned
      animals (14 dogs and 15 cats). PROCEDURES: A blood sample (3 mL) was collected
      from each animal; 2.5 mL was transferred into a vacuum tube that contained
      lithium heparin, and 0.5 mL was transferred into a microsample tube that
      contained lithium heparin. Variables evaluated were albumin, bicarbonate, BUN,
      calcium, chloride, cholesterol, creatinine, glucose, phosphorus, potassium,
      sodium, total bilirubin, and total protein concentrations and alkaline
      phosphatase, alanine aminotransferase, aspartate aminotransferase, and creatine
      kinase activities. Results for the 2 types of tubes in each species were compared
      by use of Pearson correlation coefficients, Passing-Bablok regression analysis,
      and Bland-Altman analysis. RESULTS: Data were normally distributed, except for
      creatine kinase activity of cats. The Pearson correlation coefficient was minimal
      for total bilirubin concentration in cats and moderate, high, or very high for
      all other variables. Constant bias for cholesterol and glucose concentration in
      dogs was identified during Bland-Altman analysis, although the mean difference
      between types of blood collection tubes was small. No constant or proportional
      bias for any other variable was revealed by regression analysis or Bland-Altman
      analysis. CONCLUSIONS AND CLINICAL RELEVANCE: Samples obtained from healthy dogs
      and cats by use of microsample blood collection tubes that contained lithium
      heparin provided clinically equivalent biochemical results, compared with results
      for samples obtained by use of standard blood collection tubes, and minimized the
      total sample volume collected for diagnostic testing.

PMID- 20673110
TI  - Detection of antibodies against Leptospira serovars via microscopic agglutination
      tests in dogs in the United States, 2000-2007.
AB  - OBJECTIVE: To use results of microscopic agglutination tests (MATs) conducted at
      a commercial veterinary diagnostic laboratory to determine temporal and
      demographic distributions of positive serologic test results for leptospirosis in
      dogs and identify correlations among results for various Leptospira serovars.
      DESIGN: Serosurvey. STUDY POPULATION: MAT results for 33,119 canine serum samples
      submitted to a commercial veterinary diagnostic laboratory from 2000 through
      2007. PROCEDURES: Electronic records of MAT results for dogs were obtained from a
      veterinary diagnostic laboratory. Seropositivity for antibodies against
      Leptospira serovars was determined by use of a cutoff titer of >or=1:1,600 to
      reduce the possible impact of postvaccinal antibodies on results. Correlations
      between results for all possible pairs of serovars were calculated by ordinal
      ranking of positive (>or=1:100) antibody titer results. RESULTS: 2,680 samples
      (8.1%; 95% confidence interval [CI], 7.8% to 8.4%) were seropositive for
      antibodies against Leptospira serovars. The highest percentage of positive MAT
      results was for the year 2007 (10.2%; 95% CI, 9.5% to 10.9%) and for the months
      of November and December during the study period. Antibodies were most common
      against serovars Autumnalis, Grippotyphosa, Pomona, and Bratislava.
      Seroprevalence of leptospirosis was lowest for dogs>10 years of age but was
      similar across other age strata. CONCLUSIONS AND CLINICAL RELEVANCE:
      Leptospirosis can affect dogs of small and large breeds and various ages.
      Although an increase in proportions of positive MAT results was evident in the
      fall, monthly and annual variations suggested potential exposure in all months.
      Because of the limitations of MAT results and the limited number of serovars used
      in the test, bacterial culture should be used to identify infective Leptospira
      serovars.

PMID- 20673111
TI  - Resolution of persistent pneumothorax by use of blood pleurodesis in a dog after
      surgical correction of a diaphragmatic hernia.
AB  - CASE DESCRIPTION: A 15-kg (33-lb) pregnant female mixed-breed dog of unknown age
      was referred because of a 10-day history of difficulty breathing. CLINICAL
      FINDINGS: Physical examination findings were dyspnea, tachypnea, decreased
      bronchovesicular sounds (bilateral), muffled heart sounds, and abdominal
      distention with palpable fetuses. Hematologic abnormalities included anemia,
      leukocytosis, and thrombocytosis. Abnormalities detected during serum biochemical
      analysis included decreases in concentrations of albumin, sodium, triglycerides,
      and total calcium and increases in activities of alkaline phosphatase, alanine
      aminotransferase, gamma-glutamyltransferase, aspartate aminotransferase, lactate
      dehydrogenase, and creatine kinase. Thoracic radiography revealed a diaphragmatic
      hernia with fetuses and a soft tissue or fluid opacity within the thoracic
      cavity. TREATMENT AND OUTCOME: Exploratory celiotomy, ovariohysterectomy, partial
      sternotomy, placement of a right-sided thoracostomy tube, and herniorrhaphy were
      performed. After surgery, pneumothorax developed, and the thoracostomy tube was
      used to remove pleural effusion and free air. The pneumothorax did not resolve
      after continuous drainage of the thoracic cavity for 4 days. Autologous blood
      pleurodesis was performed by infusion of 80 mL (6 mL/kg [2.73 mL/lb]) of whole
      blood. The pneumothorax resolved immediately after injection of the blood.
      CONCLUSIONS AND CLINICAL RELEVANCE: Blood pleurodesis was used for resolution of
      pneumothorax in a dog after correction of a diaphragmatic hernia. Blood
      pleurodesis may provide a simple, safe, and inexpensive medical treatment for
      resolution of persistent (duration>5 days) pneumothorax when surgery is not an
      option.

PMID- 20673112
TI  - Ocular findings in Quarter Horses with hereditary equine regional dermal
      asthenia.
AB  - OBJECTIVE: To compare ocular structures of Quarter Horses homozygous for
      hereditary equine regional dermal asthenia (HERDA) with those of Quarter Horses
      not affected by HERDA (control horses) and to determine the frequency of new
      corneal ulcers for horses with and without HERDA during a 4-year period. DESIGN:
      Cohort study of ocular structures and retrospective case series of horses with
      and without HERDA. ANIMALS: The cohort portion of the study involved 10 Quarter
      Horses with HERDA and 10 Quarter Horses without HERDA; the retrospective case
      series involved 28 horses with HERDA and 291 horses without HERDA. PROCEDURES:
      Ophthalmic examinations, Schirmer tear tests, tonometry, corneal pachymetry,
      histologic examinations, and scanning electron microscopy (SEM) were performed in
      cohorts of Quarter Horses with and without HERDA. Records were reviewed to
      determine the incidence of corneal ulcers in horses with and without HERDA during
      a 4-year period. RESULTS: Corneal thickness of horses with HERDA was
      significantly less than that of control horses, but tear production of horses
      with HERDA was significantly greater than that of control horses. Results of SEM
      revealed zones of disorganized, haphazardly arranged collagen fibrils in corneas
      of horses with HERDA that were not evident in corneas of control horses. The
      incidence of corneal ulcers was significantly greater for horses with HERDA than
      for horses without HERDA during the 4-year period. CONCLUSIONS AND CLINICAL
      RELEVANCE: Alterations in corneal thickness, arrangement of collagen fibers, and
      incidence of corneal ulcers indicated that abnormalities in horses with HERDA
      were not limited to the skin.

PMID- 20673113
TI  - Esophageal dysfunction in four alpaca crias and a llama cria with vascular ring
      anomalies.
AB  - CASE DESCRIPTION: 3 alpaca crias and cadavers of an alpaca cria and a llama cria
      were evaluated for evidence of esophageal dysfunction. CLINICAL FINDINGS: All 5
      crias were between 3 and 5 months of age when clinical signs developed, and all
      had a thin body condition when examined. Clinical signs included coughing,
      regurgitation, and grossly visible esophageal peristaltic waves. A barium
      esophagram was used to diagnose esophageal obstruction, megaesophagus, and a
      vascular ring anomaly (VRA). Fluoroscopy was used to evaluate deglutition,
      esophageal peristalsis, and the extent of esophageal dilation in 1 alpaca cria. A
      persistent right aortic arch was identified in 1 alpaca cria, and a left aortic
      arch with right ductus arteriosus or ligamentum arteriosum and an aberrant right
      subclavian artery were identified in the 4 remaining crias. TREATMENT AND
      OUTCOME: Surgical correction of the VRA was attempted in the 3 live alpaca crias.
      It was complicated by the conformation and location of each VRA and inaccurate
      anatomic diagnosis of the VRAs before surgery. Treatment was universally
      unsuccessful because of intraoperative complications and the persistence of
      clinical signs after surgery. CLINICAL RELEVANCE: Megaesophagus is typically an
      idiopathic condition in camelids. However, these findings suggested that camelids
      with esophageal dysfunction during the neonatal period may have a VRA. The
      prognosis is grave for camelids with VRA, and accurate anatomic diagnosis of the
      VRA via the use of advanced imaging techniques (eg, angiography, computed
      tomography, or magnetic resonance imaging) may improve the success of surgical
      intervention.

PMID- 20673114
TI  - Relative effects of juvenile and adult environmental factors on mate attraction
      and recognition in the cricket, Allonemobius socius.
AB  - Finding a mate is a fundamental aspect of sexual reproduction. To this end,
      specific-mate recognition systems (SMRS) have evolved that facilitate copulation
      between producers of the mating signal and their opposite-sex responders.
      Environmental variation, however, may compromise the efficiency with which SMRS
      operate. In this study, the degree to which seasonal climate experienced during
      juvenile and adult life-cycle stages affects the SMRS of a cricket, Allonemobius
      socius (Scudder) (Orthoptera: Gryllidae) was assessed. Results from two-choice
      behavioral trials suggest that adult ambient temperature, along with population
      and family origins, mediate variation in male mating call, and to a lesser extent
      directional response of females for those calls. Restricted maximum-likelihood
      estimates of heritability for male mating call components and for female response
      to mating call appeared statistically nonsignificant. However, appreciable
      "maternal genetic effects" suggest that maternal egg provisioning and other
      indirect maternal determinants of the embryonic environment significantly
      contributed to variation in male mating call and female response to mating calls.
      Thus, environmental factors can generate substantial variation in A. socius
      mating call, and, more importantly, their marginal effect on female responses to
      either fast-chirp or long-chirp mating calls suggest negative fitness
      consequences to males producing alternative types of calls. Future studies of
      sexual selection and SMRS evolution, particularly those focused on hybrid zone
      dynamics, should take explicit account of the loose concordance between signal
      producers and responders suggested by the current findings.

PMID- 20673115
TI  - Life histories of the seed bugs, Kleidocerys punctatus and Kleidocerys virescens.
AB  - The life cycles of the seed bugs, Kleidocerys punctatus Distant and Kleidocerys
      virescens F. (Hemiptera: Lygaeidae: Ischnorhynchinae), are reported for the first
      time. Description of all immature stages and adults are included. Adults and
      nymphs of K. punctatus are associated with several species of Alnus (Betulaceae),
      while those of K. virescens are associated with Nicotiana glauca Graham,
      Nicotiana tabacum L. (Solanaceae), and Buddleia crotonoides A. Gray and Buddleia
      sp. (Loganiaceae). Adults and nymphs feed mainly on the seeds, inside the dry
      fruit, but they also take plant juices from other reproductive and vegetative
      structures. Illustrations of the eggs, all nymphal instars, and the adults, as
      well as notes on their biology and their distribution in Mexico, are included.

PMID- 20673116
TI  - The biology and some population parameters of the grasshopper, Ronderosia bergi,
      under laboratory conditions.
AB  - Some biological and population parameters of Ronderosia bergi (Stal) (Orthoptera:
      Acrididae: Melanoplinae) were estimated by monitoring five cohorts of the first
      generation (F1) of individuals born in captivity from grasshoppers collected in
      the South of Misiones province, northeastern Argentina, and held under controlled
      conditions (30 degrees C, 14:10 L:D, 40% RH). The mean embryonic development time
      was 40.6 +/- 1.7 days. Five nymphal instars were recorded. Total duration of
      nymphal development was 30.8 +/- 0.54 days. The mean lifespan of cohorts was 22.6
      +/- 0.7 weeks. The number of egg-pods per female was 7.6 +/- 1.44, and the amount
      of eggs per egg-pod was 16.45 +/- 0.85. Mean fecundity was 125 +/- 5.83 eggs per
      female with an oviposition rate of 1.55 +/- 0.57 eggs/female/day. Survivorship
      curves showed that mortality was concentrated in the final weeks of adulthood,
      and the life expectancy curve decreased accordingly. The population parameters
      estimated gave the following values: the net rate of reproduction (R(0)) was
      46.75 +/- 11.2, generation time (T) was 18.87 +/- 1.67 weeks, duplication time
      (D) was 3.31 +/- 0.34, the intrinsic rate of population growth (r(m)) was 0.21 +/
      0.021 and the finite rate of population increase (lambda) was 1.24 +/- 0.026.
      The reproductive values (V(x)) indicated that the largest contribution of females
      to the subsequent generation was between weeks 15 and 25.

PMID- 20673117
TI  - The South American dung beetle genus Ennearabdus Lansberge (Coleoptera:
      Scarabaeidae: Scarabaeinae: Eucraniini).
AB  - The South American endemic dung beetle genus Ennearabdus Lansberge is revised.
      Description, diagnosis and illustrations are presented for the only known species
      of the genus, E. lobocephalus (Harold). A lectotype is designated for Onthophagus
      lobocephalus Harold, the type species of Ennearabdus. The biology, biogeography,
      conservation status, and distribution based on the predictive distribution model
      of E. lobocephalus are also discussed.

PMID- 20673118
TI  - Worker allometry in relation to colony size and social form in the fire ant
      Solenopsis invicta.
AB  - Workers of the polymorphic fire ant Solenopsis invicta Buren (Hymenoptera:
      Formicidae) show modest changes of shape with increases in body size. These shape
      changes (allometries) have been described only for workers taken from mature
      colonies of the monogyne social form. For the study reported here, workers were
      collected from small and large monogyne and large polygyne colonies for tests of
      the effects of colony size and social form on allometry. The differential growth
      of body parts in relation to total body growth was determined by measurement of
      all major body parts and regression of the logs of these measurements, or their
      ratios, on the log of the body size. The slopes of these regressions defined the
      allometric relationships, and the slopes for these three types of colonies were
      compared for determination of the influence of colony size and social form on
      allometric rules. Most allometric constants did not differ with colony size or
      social form, but head shape, relative antennal size, and alinotum shape did. For
      a given worker size, heads of workers from small monogyne colonies or from
      polygyne colonies were narrower above the eyes. Antennae of workers from large
      monogyne colonies were relatively shorter than those from small monogyne or
      polygyne colonies (which did not differ). Alinotum heights of small workers from
      small monogyne colonies were greater than those from large monogyne or polygyne
      colonies (which were isometric and did not differ). These observed differences in
      allometric constants suggest that the relative growth rules are not completely
      determined by worker body size but are affected by colony size and social form.
      These differences are discussed in light of the growth of imaginai discs under
      conditions of fixed resources.

PMID- 20673119
TI  - Genetics of color polymorphism in the pea aphid, Acyrthosiphon pisum.
AB  - The genetic basis of color polymorphism is explored in the pea aphid,
      Acyrthosiphon pisum (Harris) (Homoptera: Sternorrhyncha), in which two color
      morphs have been described (pink or green). Laboratory crosses and a Mendelian
      genetic analysis reveal that color polymorphism in pea aphids is determined by a
      single biallelic locus, which we name colorama, with alleles P and p, pink being
      dominant to green. The putative genotypes are Pp or PP for pink morphs, and pp
      for green morphs. This locus is shown to be autosomal. Last, there was no
      evidence of influence of the direction of the cross on color inheritance, thus
      showing that cytoplasmic effects and/or maternally-inherited symbionts play no
      role in the inheritance of color polymorphism in pea aphids. The existence of a
      simple genetic determinism for color polymorphism in a system in which genetic
      investigation is possible may facilitate investigations on the physiological and
      molecular mechanisms of genetically-based color morph variation, and the
      establishment of a link between this locus and fitness in a range of ecological
      conditions.

PMID- 20673120
TI  - Formulae for insect wingbeat frequency.
AB  - A formula is developed connecting the wingbeat frequency of insects with their
      masses and wing areas. It is derived first theoretically, using dimensional
      analysis, and then it is compared with published measurements. The formula
      discovered involves two parameters which dimensional analysis alone cannot
      determine. One of these is evaluated using one among many proposed semi-empirical
      relationships (the only one that stands scrutiny); the other by fitting a
      published dataset. It is found that the resulting equation, applying to insects
      in general, accords well with observation, and indeed is very close to being
      optimal (in a sense to be defined).

PMID- 20673121
TI  - Effect of temperature on the development and survival of the Argentine ant,
      Linepithema humile.
AB  - The influence of temperature on the developmental times and survival of insects
      can largely determine their distribution. For invasive species, like the
      Argentine ant, Linepithema humile Mayr (Hymenoptera: Formicidae), these data are
      essential for predicting their potential range based on mechanistic models. In
      the case of this species, such data are too scarce and incomplete to make
      accurate predictions based on its physiological needs. This research provides
      comprehensive new data about brood survival and developmental times at a wide
      range of temperatures under laboratory conditions. Temperature affected both the
      complete brood development from egg to adult worker and each of the immature
      stages separately. The higher the temperature, the shorter the development times.
      Brood survival from egg to adult was low, with the maximum survival rate being
      only 16% at 26 degrees C. Temperature also affected survival of each of the
      immature stages differently: eggs were negatively affected by high temperatures,
      while larvae were negatively affected by low temperatures, and the survival of
      pupae was apparently independent of environmental temperature. At 32 degrees C no
      eggs survived, while at 18 degrees C less than 2% of the eggs hatched into larva.
      The data from the present study are essential for developing prediction models
      about the distribution range of this tramp species based on its physiological
      needs in relation to temperature.

PMID- 20673122
TI  - Efficacy of pitfall trapping, Winkler and Berlese extraction methods for
      measuring ground-dwelling arthropods in moist-deciduous forests in the Western
      Ghats.
AB  - The present study provides data to decide on the most appropriate method for
      sampling of ground-dwelling arthropods measured in a moist-deciduous forest in
      the Western Ghats in South India. The abundance of ground-dwelling arthropods was
      compared among large numbers of samples obtained using pitfall trapping, Berlese
      and Winkler extraction methods. Highest abundance and frequency of most of the
      represented taxa indicated pitfall trapping as the ideal method for sampling of
      ground-dwelling arthropods. However, with possible bias towards surface-active
      taxa, pitfall-trapping data is inappropriate for quantitative studies, and
      Berlese extraction is the better alternative. Berlese extraction is the better
      method for quantitative measurements than the other two methods, whereas pitfall
      trapping would be appropriate for qualitative measurements. A comparison of the
      Berlese and Winkler extraction data shows that in a quantitative multigroup
      approach, Winkler extraction was inferior to Berlese extraction because the total
      number of arthropods caught was the lowest; and many of the taxa that were caught
      from an identical sample via Berlese extraction method were not caught.
      Significantly a greater frequency and higher abundance of arthropods belonging to
      Orthoptera, Blattaria, and Diptera occurred in pitfall-trapped samples and
      Psocoptera and Acariformes in Berlese-extracted samples than that were obtained
      in the other two methods, indicating that both methods are useful, one
      complementing the other, eliminating a chance for possible under-representation
      of taxa in quantitative studies.

PMID- 20673123
TI  - Effects of intra- and interpatch host density on egg parasitism by three species
      of Trichogramma.
AB  - Host-foraging responses to different intra- and interpatch densities were used to
      assess three Trichogramma spp. (Hymenoptera: Trichogrammatidae) Trichogramma
      deion Pinto and Oatman, T. ostriniae Pang and Chen, and T. pretiosum Riley - as
      potential biological control agents for the Indian meal moth, Plodia
      interpunctella Hubner (Lepidoptera: Pyralidae). Single naive females were allowed
      6 h to forage in Plexiglas arenas with four different spatial arrangements of
      host eggs, nine single-egg patches), nine four-egg patches, 36 single-egg
      patches, and 36 four-egg patches. No significant differences were found among
      species in the number of patches parasitized. As expected, all three species
      parasitized the most eggs in the 36 four-egg patch treatment and the least in the
      nine single-egg patch treatment. T. deion parasitized significantly more eggs
      than T. pretiosum on the nine four-egg patches. T. ostriniae parasitized
      significantly more patches when intrapatch density was greater, regardless of
      interpatch density. In contrast, T. deion only parasitized more patches at the
      greater intrapatch density when the interpatch density was low. Patch density had
      no effect on T. pretiosum. The spatial pattern of parasitism was more aggregated
      for T. deion and T. ostriniae in the 36 four-egg patches treatment compared to
      the 36 single-egg patches treatment. Therefore, intrapatch density was more
      important than interpatch density for T. ostriniae, and potentially for T. deion,
      but not for T. pretiosum. T. deion may be the best candidate for augmentative
      biological control because it parasitized either slightly or significantly more
      eggs than the other two species in all four treatments. Furthermore, the pattern
      of parasitism by T. deion in the 36 four-egg patches treatment was the most
      aggregated among the three species, suggesting a more thorough searching pattern.
      In contrast, T. pretiosum had the least aggregated pattern of parasitism and
      therefore may have used a more random foraging pattern.

PMID- 20673124
TI  - The extending network of FOXO transcriptional target genes.
AB  - The evolutionarily conserved Forkhead box O (FOXO) family of transcription
      factors regulates multiple transcriptional targets involved in various cellular
      processes, including proliferation, stress resistance, apoptosis, and metabolism.
      Target gene regulation appears to be controlled in a cell-type-specific manner
      due to association of FOXO isoforms with specific cofactors. Many of the cellular
      processes modulated by FOXO are themselves deregulated in tumorigenesis, and
      deletion of Foxo genes has demonstrated that these transcription factors function
      as tumor suppressors. Our understanding of the regulation of FOXO activity, and
      defining specific transcriptional targets, may provide clues to the molecular
      mechanisms controlling cell fate decisions. In this review we describe the
      functional consequences of FOXO activation based on our current knowledge of
      transcriptional targets.

PMID- 20673125
TI  - Nitroxyl (HNO) as a vasoprotective signaling molecule.
AB  - Nitroxyl (HNO), the one electron reduced and protonated form of nitric oxide
      (NO(*)), is rapidly emerging as a novel nitrogen oxide with distinct pharmacology
      and therapeutic advantages over its redox sibling. Whilst the cardioprotective
      effects of HNO in heart failure have been established, it is apparent that HNO
      may also confer a number of vasoprotective properties. Like NO(*), HNO induces
      vasodilatation, inhibits platelet aggregation, and limits vascular smooth muscle
      cell proliferation. In addition, HNO can be putatively generated within the
      vasculature, and recent evidence suggests it also serves as an endothelium
      derived relaxing factor (EDRF). Significantly, HNO targets signaling pathways
      distinct from NO(*) with an ability to activate K(V) and K(ATP) channels in
      resistance arteries, cause coronary vasodilatation in part via release of
      calcitonin-gene related peptide (CGRP), and exhibits resistance to scavenging by
      superoxide and vascular tolerance development. As such, HNO synthesis and
      bioavailability may be preserved and/or enhanced during disease states, in
      particular those associated with oxidative stress. Moreover, it may compensate,
      in part, for a loss of NO(*) signaling. Here we explore the vasoprotective
      actions of HNO and discuss the therapeutic potential of HNO donors in the
      treatment of vascular dysfunction.

PMID- 20673126
TI  - Highly specialized role of Forkhead box O transcription factors in the immune
      system.
AB  - Recent studies have highlighted a fundamental role for Forkhead box O (Foxo)
      transcription factors in immune system homeostasis. Initial reports designed to
      dissect function of individual Foxo isoforms in the immune system were based on
      in vitro overexpression systems, and these experiments suggested that Foxo1 and
      Foxo3 are important for growth factor withdrawal-induced cell death. Moreover,
      Foxo factors importantly regulate basic cell cycle progression, and so the
      implication was that these factors may control lymphocyte homeostasis, including
      a critical function in the termination and resolution of an immune response. Most
      recently, cell-type-specific loss mutants for the different Foxo isoforms have
      revealed unexpected and highly specialized functions in the control of multiple
      cell types in the immune system, but they have yet to reveal a role in cell death
      or proliferation. This review will focus on the recent advances made in the
      understanding of the many ways that Foxo factors regulate the immune system,
      including a discussion of how the specialized versus redundant functions of Foxo
      transcription factors impact immune system homeostasis.

PMID- 20673128
TI  - Genetic dysregulation of glutathione synthesis predicts alteration of plasma
      thiol redox status in schizophrenia.
AB  - Genetic studies have shown an association between schizophrenia and a GAG
      trinucleotide repeat (TNR) polymorphism in the catalytic subunit (GCLC) of the
      glutamate cysteine ligase (GCL), the key enzyme for glutathione (GSH) synthesis.
      The present study was aimed at analyzing the influence of a GSH dysregulation of
      genetic origin on plasma thiols (total cysteine, homocysteine, and cysteine
      glycine) and other free amino acid levels as well as fibroblast cultures GSH
      levels. Plasma thiols levels were also compared between patients and controls. As
      compared with patients with a low-risk GCLC GAG TNR genotype, patients with a
      high-risk genotype, having an impaired GSH synthesis, displayed a decrease of
      fibroblast GSH and plasma total cysteine levels, and an increase of the oxidized
      form of cysteine (cystine) content. Increased levels of plasma free serine,
      glutamine, citrulline, and arginine were also observed in the high-risk genotype.
      Taken together, the high-risk genotypes were associated with a subgroup of
      schizophrenia characterized by altered plasma thiols and free amino acid levels
      that reflect a dysregulation of redox control and an increased susceptibility to
      oxidative stress. This altered pattern potentially contributes to the development
      of a biomarker profile useful for early diagnosis and monitoring the
      effectiveness of novel drugs targeting redox dysregulation in schizophrenia.

PMID- 20673129
TI  - Radiobiological basis in management of accidental radiation exposure.
AB  - PURPOSE: With increasing utilisation of nuclear technologies in power production,
      medical and industrial applications, and in a scenario of nuclear terrorism/war,
      there is an enhanced likelihood of accidental radiation exposure to occupational
      workers, patients and public. The consequent health effects of the radiation
      exposure are resultant of interaction of radiation with biological systems and
      subsequent radiation injury. The present review discusses the knowledge gained in
      radiation biology that can be exploited for better treatment and management of
      radiation accident victims. RESULTS: In comparison with planned radiation
      exposure during diagnosis/therapy, the management of accidental radiation
      exposure is quite complicated due to uncertainties in dose, duration, organs
      involved and radionuclides internalised, and hence, require multi-faceted
      approaches. However, the options available for dosimetry, decorporation of
      radionuclides and therapeutic protocols of patients are limited, which provides
      substantial scope in these areas of research. Moreover, there is a need to fill
      the gaps in knowledge of radiation action in different dose ranges and post
      irradiation windows, which would help in improving therapeutic approaches.
      Cytogenetic approaches are 'gold standard' for biodosimetry but with limited
      applications in mass casualty scenario. State-of-the-art technological
      advancement and high throughput in metabolomics, proteomics and genomics could be
      employed successfully in developing better biodosimetry for triage in accidental
      radiation exposure. Furthermore, identification of targets at organs/organelles
      level of internalised radionuclides would be helpful to develop effective
      decorporation strategies. Despite substantial research investigating several
      agents, which could modify radiation effects, only a few could reach up to
      practical application due to poor bioavailability or toxicity. CONCLUSIONS:
      Deeper insight into the mechanisms of radiation injury under accidental radiation
      conditions would be helpful in achieving better biodosimetry, decorporation
      strategies and improvement in prevention/post-irradiation management of radiation
      accident patients.

PMID- 20673127
TI  - Cellular and molecular determinants of stroke-induced changes in subventricular
      zone cell migration.
AB  - A remarkable aspect of adult neurogenesis is that the tight regulation of
      subventricular zone (SVZ) neuroblast migration is altered after ischemic stroke
      and newborn neurons emigrate towards the injury. This phenomenon is an essential
      component of endogenous repair and also serves to illuminate normal mechanisms
      and rules that govern SVZ migration. Stroke causes inflammation that leads to
      cytokine and chemokine release, and SVZ neuroblasts that express their receptors
      are recruited. Metalloproteinases create pathways and new blood vessels provide a
      scaffold to facilitate neuroblast migration between the SVZ and the infarct. Most
      experiments have studied the peri-lesion parenchyma and relatively little is
      known about SVZ remodeling after stroke. Migration in the SVZ is tightly
      regulated by cellular interactions and molecular signaling; how are these altered
      after stroke to allow emigration? Do ependymal cells contribute to this process,
      given their reported neurogenic potential? How does stroke affect ependymal cell
      regulation of cerebrospinal fluid flow? Given the heterogeneity of SVZ
      progenitors, do all types of neuroblasts migrate out, or is this confined to
      specific subtypes of cells? We discuss these and other questions in our review
      and propose experiments to address them.

PMID- 20673130
TI  - The expression of p53-regulated genes in human cultured lymphoblastoid TSCE5 and
      WTK1 cell lines during spaceflight.
AB  - PURPOSE: The space environment contains two major biologically significant
      influences; space radiations and microgravity. The 53 kDa tumour suppressor
      protein (p53) plays a role as a guardian of the genome through the activity of
      p53-centered signal transduction pathways. The aim of this study was to clarify
      the biological effects of space radiations, microgravity, and the space
      environment on the gene expression of p53-regulated genes. MATERIALS AND METHODS:
      Space experiments were performed with two human cultured lymphoblastoid cell
      lines; one line (TSCE5) bears a wild-type p53 gene status, and another line
      (WTK1) bears a mutated p53 gene status. Under one gravity or microgravity
      conditions, the cells were grown in the cell biology experimental facility (CBEF)
      of the International Space Station for 8 days without experiencing stress during
      launching and landing because the cells were frozen during these periods. Ground
      control samples also were cultured for 8 days in the CBEF on the ground during
      the spaceflight. Gene expression was analysed using an Agilent Technologies 44 k
      whole human genome microarray DNA chip. RESULTS: p53-dependent up-regulated gene
      expression was observed for 111, 95, and 328 genes and p53-dependent down
      regulated gene expression was found for 177, 16, and 282 genes after exposure to
      space radiations, to microgravity, and to both, respectively. CONCLUSIONS: The
      data provide the p53-dependent regulated genes by exposure to radiations and/or
      microgravity during spaceflight. Our expression data revealed genes that might
      help to advance the basic space radiation biology.

PMID- 20673132
TI  - Enhanced proliferation and migration of fibroblasts on the surface of fibroblast
      growth factor-2-loaded fibrin microthreads.
AB  - Fibrin microthreads are discrete biopolymer fibers, 50-100 MUm in diameter,
      produced from the natural extracellular matrix protein of the provisional matrix
      that promotes tissue regeneration in the in vivo wound healing environment. The
      goals of this study were to investigate the feasibility of creating fibrin
      microthreads containing fibroblast growth factor-2 (FGF-2), and to study the
      potential of a fibrin matrix to bind signaling proteins known to promote wound
      healing and regulate cell function in localized cellular microenvironments on
      scaffold surfaces. FGF-2 was loaded into fibrin microthreads in concentrations
      ranging from 0 to 200 ng/mL, to investigate the effect of the material on
      fibroblast attachment, proliferation, cellular outgrowth, and alignment. Although
      FGF-2-loaded microthreads did not affect fibroblast attachment, they
      significantly increased cellular outgrowth and proliferation relative to unloaded
      microthreads. The most pronounced effects were observed at day 7 of cell culture.
      Further, all of the fibrin microthreads promoted the alignment of fibroblasts and
      their cytoskeletal components along the long axis of threads, independent of the
      FGF-2 concentration. Ultimately, we anticipate that these fibrin microthreads
      will be a promising biopolymer material to promote the regeneration of injured
      tissues because of their mechanical stability and their matrix signaling
      capabilities, particularly when loaded with matrix-bound growth factors such as
      FGF-2.

PMID- 20673131
TI  - Extracellular matrix fibronectin stimulates the self-assembly of microtissues on
      native collagen gels.
AB  - Fibronectin is an adhesive glycoprotein that is polymerized into extracellular
      matrices via a tightly regulated, cell-dependent process. Here, we demonstrate
      that fibronectin matrix polymerization induces the self-assembly of multicellular
      structures in vitro, termed tissue bodies. Fibronectin-null mouse embryonic
      fibroblasts adherent to compliant gels of polymerized type I collagen failed to
      spread or proliferate. In contrast, addition of fibronectin to collagen-adherent
      fibronectin-null mouse embryonic fibroblasts resulted in a dose-dependent
      increase in cell number, and induced the formation of three-dimensional (3D)
      multicellular structures that remained adherent and well-spread on the native
      collagen substrate. An extensive fibrillar fibronectin matrix formed throughout
      the microtissue. Blocking fibronectin matrix polymerization inhibited both cell
      proliferation and microtissue formation, demonstrating the importance of
      fibronectin fibrillogenesis in triggering cellular self-organization. Cell
      proliferation, tissue body formation, and tissue body shape were dependent on
      both fibronectin and collagen concentrations, suggesting that the relative
      proportion of collagen and fibronectin fibrils polymerized into the extracellular
      matrix influences the extent of cell proliferation and the final shape of
      microtissues. These data demonstrate a novel role for cell-mediated fibronectin
      fibrillogenesis in the formation and vertical assembly of microtissues, and
      provide a novel approach for engineering complex tissue architecture.

PMID- 20673133
TI  - Transwells with microstamped membranes produce micropatterned two-dimensional and
      three-dimensional co-cultures.
AB  - This article describes a simple and rapid cell patterning method to form co
      culture microarrays in commercially available Transwells. A thin
      poly(dimethylsiloxane) (PDMS) layer is printed on the underside of a Transwell
      using a PDMS stamp. Arbitrary cellular patterns are generated according to the
      geometric features of the thin PDMS layer through hydrodynamic forces that guide
      cells onto the membrane only over the PDMS-uncoated regions. Micropatterns of
      surface-adhered cells (we refer to this as two-dimensional) or non-surface
      adhered clusters of cells (we refer to this as three-dimensional) can be
      generated depending on the surface treatment of the filter membrane.
      Additionally, co-cultures can be established by introducing different types of
      cells on the membrane or in the bottom chamber of the Transwell. We show that
      this co-culture method can evaluate mouse embryonic stem (mES) cell
      differentiation based on heterogeneous cell-cell interactions. Co-culture of mES
      cells and HepG2 cells decreased SOX17 expression of mES cells, and direct cell
      cell contact further decreased SOX17 expression, indicating that co-culture with
      HepG2 cells inhibits endoderm differentiation through soluble factors and cell
      cell contact. This method is simple and user-friendly and should be broadly
      useful to study cell shapes and cell-cell interactions. 

PMID- 20673134
TI  - Hypoxia and amino acid supplementation synergistically promote the osteogenesis
      of human mesenchymal stem cells on silk protein scaffolds.
AB  - Tailoring tissue engineering strategies to match patient- and tissue-specific
      bone regeneration needs offers to improve clinical outcomes. As a step toward
      this goal, osteogenic outcomes and metabolic parameters were assessed when
      varying inputs into the bone formation process. Silk protein scaffolds seeded
      with human mesenchymal stem cells in osteogenic differentiation media were used
      to study in vitro osteogenesis under varied conditions of amino acid (lysine and
      proline) concentration and oxygen level. The cells were assessed to probe how the
      microenvironment impacted metabolic pathways and thus osteogenesis. The most
      favorable osteogenesis outcomes were found in the presence of low (5%) oxygen
      combined with high lysine and proline concentrations during in vitro cultivation.
      This same set of culture conditions also showed the highest glucose consumption,
      lactate synthesis, and certain amino acid consumption rates. On the basis of
      these results and known pathways, a holistic metabolic model was derived which
      shows that lysine and proline supplements as well as low (5%) oxygen levels
      regulate collagen matrix synthesis and thereby rates of osteogenesis. This study
      establishes early steps toward a foundation for patient- and tissue-specific
      matches between metabolism, repair site, and tissue engineering approaches toward
      optimized bone regeneration.

PMID- 20673135
TI  - Fabrication of Off-the-Shelf Multilumen Poly(Ethylene Glycol) Nerve Guidance
      Conduits Using Stereolithography.
AB  - A manufacturing process for fabricating off-the-shelf multilumen poly(ethylene
      glycol) (PEG)-based nerve guidance conduits (NGCs) was developed that included
      the use of stereolithography (SL). A rapid fabrication strategy for complex 3D
      scaffolds incorporated postprocessing with lyophilization and sterilization to
      preserve the scaffold, creating an implantable product with improved
      suturability. SL is easily adaptable to changes in scaffold design, is compatible
      with various materials and cells, and can be expanded for mass manufacture. The
      fabricated conduits were characterized using optical and scanning electron
      microscopy, and measurements of swelling ratio, dimensional swelling factor,
      resistance to compression, and coefficient of friction were performed. Water
      absorption curves showed that the conduits after lyophilization and sterilization
      return easily and rapidly to a swollen state when placed in an aqueous solution,
      successfully maintaining their original overall structure as required for
      implantation. Postprocessed conduits at the swollen state were less slippery and
      therefore easier to handle than those without postprocessing. Suture pullout
      experiments showed that NGCs fabricated with a higher concentration of PEG were
      better able to resist suture pullout. NGCs having a multilumen design
      demonstrated a better resistance to compression than a single-lumen design with
      an equivalent surface area, as well as a greater force required to collapse the
      design. Conduits fabricated with a higher PEG concentration were shown to have
      compressive resistances comparable to those of commercially available NGCs. The
      use of SL with PEG and the manufacturing process developed here shows promise for
      improving the current state of the art in peripheral nerve repair strategies. 

PMID- 20673136
TI  - Osteogenic differentiation of human Wharton's jelly stem cells on nanofibrous
      substrates in vitro.
AB  - Most tissue engineering studies use human bone marrow mesenchymal stem cells for
      differentiation into desirable lineages. We derived a novel stem cell from the
      human umbilical cord Wharton's jelly (hWJSC) that has numerous advantages over
      other stem cell types in that they can be harvested in abundance very efficiently
      and painlessly with no risk of patient morbidity, have prolonged stemness
      properties in vitro, are hypoimmunogenic, and can be differentiated into many
      tissue types in two-dimensional culture. We compared four different three
      dimensional nanofibrous scaffolds (polycaprolactone [PCL], PCL/collagen
      [PCL/Coll], PCL/hydroxyapatite [PCL/HA], and PCL/Coll/HA) for the attachment,
      proliferation, differentiation, and mineralization of hWJSCs into an osteogenic
      lineage. The collagen-based scaffolds (PCL/Coll and PCL/Coll/HA) showed better
      cell attachment and proliferation than PCL and PCL/HA, with increases of 41.80%
      and 38.52%, respectively. hWJSCs cultured on PCL/Coll/HA in the osteogenic medium
      up to 21 days demonstrated increased alkaline phosphatase activity and greater
      expression of osteocalcin, mineralization, and osteogenic-related genes compared
      to controls. Given the advantages of hWJSCs over other stem cell types, we
      propose that hWJSCs may be efficiently differentiated into an osteogenic lineage
      on a three-dimensional PCL/Coll/HA nanofibrous scaffold for the treatment of bone
      defects.

PMID- 20673137
TI  - Establishment of immortal multipotent rat salivary progenitor cell line toward
      salivary gland regeneration.
AB  - Adult salivary gland stem cells are promising candidates for cell therapy and
      tissue regeneration in cases of irreversible damage to salivary glands in head
      and neck cancer patients undergoing irradiation therapy. At present, the major
      restriction in handling such cells is their relatively limited life span during
      in vitro cultivation, resulting in an inadequate experimental platform to explore
      the salivary gland-originated stem cells as candidates for future clinical
      application in therapy. We established a spontaneous immortal integrin
      alpha6beta1-expressing cell line of adult salivary progenitor cells from rats
      (rat salivary clone [RSC]) and investigated their ability to sustain cellular
      properties. This line was able to propagate for more than 400 doublings without
      loss of differentiation potential. RSC could differentiate in vitro to both
      acinar- and ductal-like structures and could be further manipulated upon
      culturing on a 3D scaffolds with different media supplements. Moreover, RSC
      expressed salivary-specific mRNAs and proteins as well as epithelial stem cell
      markers, and upon differentiation process their expression was changed. These
      results suggest RSC as a good model for further studies exploring cellular
      senescence, differentiation, and in vitro tissue engineering features as a
      crucial step toward reengineering irradiation-impaired salivary glands. 

PMID- 20673138
TI  - Isolation and characterization of mesenchymal stem cells from human amniotic
      membrane.
AB  - INTRODUCTION: The human amniotic membrane is a highly abundant and readily
      available tissue that may be useful for regenerative medicine and cell therapy.
      AIM: To compare two previously published protocols for the isolation of human
      amnion mesenchymal stromal cells (hAMSCs), including their phenotypic
      characterization and in vitro potential for differentiation toward osteogenic,
      adipogenic, and chondrogenic mesodermal lineages. MATERIALS AND METHODS: Human
      placentas were obtained from selected caesarean-sectioned births. Two different
      protocols (Alviano et al. (1) and Soncini et al. (2) ) for the isolation of
      hAMSCs were performed. After monolayer expansion of adherent cells from both
      protocols, the cells were characterized by flow cytometry and for
      multipotentiality, as assessed by their capability to differentiate toward
      adipocyte-, osteoblast-, and chondrocyte-like cells. RESULTS: Both protocols
      yielded hAMSCs that showed plastic adherence, fibroblast-like growth, and well
      defined human MSC markers. The cell yield and mesodermal differentiation
      capability of hAMSCs were higher in cells isolated using the Soncini protocol.
      CONCLUSIONS: Our data demonstrated the successful isolation of hAMSCs from full
      term placentas using two published protocols. Differences between the two
      protocols in cell yield and in vitro differentiation potential are shown.

PMID- 20673139
TI  - Treatment of oral florid papillomatosis with systemic administration of
      photocarcinorin: an effective photodynamic therapy.
AB  - OBJECTIVES: To evaluate the safety and effect of systemic administration of
      photosensitizer Photocarcinorin (PsD-007) in the treatment of oral florid
      papillomatosis (OFP). BACKGROUND: OFP is a rare and refractory disease
      characterized by multiple papillomatous lesions. The outcomes of many methods for
      OFP are not satisfactory. MATERIALS AND METHODS: Photosensitizer Photocarcinorin
      (5 mg/kg) was intravenously injected into a 59-year-old woman with widespread
      OFP, and the lesions were irradiated for 10 min by using a 635-nm laser beam of
      177 mW/cm(2) intensity and 106.2 J/cm(2) energy density. The therapy was
      performed once a month for 3 months in total. RESULTS: After three courses, the
      small lesions disappeared, and the larger ones were reduced by >=80%. The adverse
      effects were minimal. CONCLUSIONS: Systemic PDT is an effective and successful
      treatment modality for OFP, especially in elderly patients.

PMID- 20673140
TI  - Is oral administration of Chinese herbal medicine effective and safe as an
      adjunctive therapy for managing diabetic foot ulcers? A systematic review and
      meta-analysis.
AB  - OBJECTIVE: This meta-analysis aimed to assess the effectiveness and safety of
      Chinese herbal medicine (CHM) as an adjunctive method to standard therapy for
      patients with diabetic foot ulcers (DFU). METHODS: Randomized controlled trials
      (RCTs) of CHM to treat DFU were searched in the following electronic databases:
      MEDLINE; EMBASE; Chinese Biomedical Database (CBM); Cochrane Central Register of
      Controlled Trials (CENTRAL); Allied & Complementary Medicine Resources (AMED);
      and Cumulative Index to Nursing and Allied Health Literature (CINAHL). Two (2)
      researchers independently assessed the quality and validity of included trials
      and extracted outcome data for synthesis. RESULTS: Six (6) trials were included
      for analysis. Compared to using standard therapy alone, CHM combined with
      standard therapy significantly increased the number of patients whose ulcers
      healed (risk ratio [RR], 0.62, [95% confidence interval (CI), 0.39-0.97]) and
      number of patients with at least a 30% reduction in the ulcer area (RR, 0.81
      [95%CI, 0.71-0.92]). In addition, the two therapies combined significantly
      decreased the number of patients without any improvement (RR, 0.34 [95%CI, 0.21
      0.53]). However, with respect to blood flow volume in the dorsal artery of the
      foot, no significant difference between the two therapies was observed
      (standardized mean difference, 1.71 [95% CI -1.25-4.67]), but the result favored
      the CHM combined with standard therapy group. Only 2 of 6 trials reported adverse
      events, which included nausea, epigastric pain, and dry mouth. CONCLUSIONS: CHM
      may be effective and safe as an adjunctive therapy for treating DFU. However, a
      firm conclusion could not be reached because of the poor quality of the included
      trials. Further trials with higher quality are justified.

PMID- 20673141
TI  - The acute effect of acupuncture on endothelial dysfunction in patients with
      hypertension: a pilot, randomized, double-blind, placebo-controlled crossover
      trial.
AB  - OBJECTIVES: The objective of the study was to test whether acupuncture improves
      endothelial dysfunction in patients with hypertension and compare the effects of
      different acupoints to find out which one is the most suitable for the long-term
      follow-up study. DESIGN: This study is a pilot, randomized, double-blind, placebo
      controlled crossover trial. Subjects were randomly assigned to a sequence of four
      acupuncture treatment phases, each for 15 minutes with a 7-day washout period in
      between. Acupuncture needles were inserted at bilateral ST 36; PC 6; ST 36 plus
      PC 6; and placebo points. SUBJECTS: Fifteen (15) patients with essential
      hypertension were the subjects. OUTCOME MEASURES: Flow-mediated dilation (FMD)
      and blood pressure were assessed before and after acupuncture treatment. RESULTS:
      FMD significantly improved with the acupuncture treatment at ST 36 (0.266 +/-
      0.078 mm to 0.306 +/- 0.077 mm, p = 0.003) and ST 36 plus PC 6 (0.284 +/- 0.098
      mm to 0.332 +/- 0.103 mm, p < 0.001). In contrast, FMD was unchanged after the
      acupuncture treatment at PC 6 or the placebo treatment. The FMD response to the
      acupuncture treatment at ST 36 plus PC 6 was significantly different from the
      response to the acupuncture treatment at PC 6 and the placebo treatment (p <
      0.05, p < 0.01, respectively). The acupuncture treatment at ST 36 significantly
      increased FMD compared to the placebo treatment (p < 0.05). CONCLUSIONS: This
      study demonstrates that the acute treatment of acupuncture in hypertensive
      patients improves endothelial dysfunction. The beneficial effect of acupuncture
      could be of clinical importance to prevent the progression of cardiovascular
      diseases in hypertensive patients. However, the potential role of acupuncture
      treatment for long-term therapy has not been examined. Further studies will be
      necessary to demonstrate whether long-term acupuncture treatment can sustain the
      improvement in endothelial dysfunction.

PMID- 20673142
TI  - Relationship of body composition, metabolic status, antiretroviral use, and HIV
      disease factors to endothelial dysfunction in HIV-infected subjects.
AB  - Vascular endothelial dysfunction may contribute to the increase in cardiovascular
      events during HIV-1 infection and its treatment. Antiretroviral therapy (ART),
      metabolic factors, lipodystrophy, and HIV infection itself may be involved.
      Ninety-six HIV-infected subjects were evaluated for endothelial function by
      measurement of brachial artery flow-mediated dilation (FMD) by ultrasound, single
      slice CT of the abdomen and mid-thigh, whole-body dual x-ray absorptiomety (DXA)
      scans, and metabolic evaluations in a cross-sectional study. The median age was
      40 years; 28% were female, 38% black, 3% Hispanic, and 59% white. Forty-nine
      (51%) were receiving ART, which included a PI in 28 (57%) and was non-PI based in
      21 (43%). FMD (+/-SD) in subjects not on ART was 5.5 +/- 4.3%, PI-ART 5.3 +/-
      3.6%, and non-PI-ART 5.5 +/- 4.1% (p = 0.9). Age, race, CD4 cell count, and HIV
      RNA did not correlate significantly with FMD. Among ART-treated subjects in the
      lowest tertile of thigh subcutaneous fat area (range 3-31 cm(2)), FMD was 4.4 +/-
      3.5% and in the highest tertile (range 67-237 cm(2)) FMD was 6.8 +/- 3.6% (p =
      0.07, t-test). However, in multivariate analyses, no body composition measure
      showed a significant association with FMD for either the group as a whole or in
      ART-treated subjects. ART use, PI use, CD4 cell count, and HIV RNA levels were
      not associated with endothelial dysfunction by brachial FMD. A definitive
      association with measures of adiposity was not detected in multivariate analysis,
      suggesting that lipoatrophy may not be an important contributor to endothelial
      dysfunction in HIV-infected individuals on ART.

PMID- 20673143
TI  - HIV infection among U.S. Army and Air Force military personnel: sociodemographic
      and genotyping analysis.
AB  - Since 1985, the U.S. Department of Defense has periodically screened all military
      personnel for HIV allowing for the monitoring of the infection in this dynamic
      cohort population. A nested case-control study was performed to study
      sociodemographics, overseas assignment, and molecular analysis of HIV. Cases were
      newly identified HIV infections among U.S. Army and Air Force military personnel
      from 2000 to 2004. Controls were frequency matched to cases by gender and date of
      case first positive HIV screening test. Genotyping analysis was performed using
      high-throughput screening assays and partial genome sequencing. HIV was
      significantly associated with black race [odds ratio (OR) = 6.65], single marital
      status (OR = 4.45), and age (OR per year = 1.07). Ninety-seven percent were
      subtype B and 3% were non-B subtypes (A3, CRF01_AE, A/C recombinant, G,
      CRF02_AG). Among cases, overseas assignment in the period at risk prior to their
      first HIV-positive test was associated with non-B HIV subtype infection (OR =
      8.44). Black and single military personnel remain disproportionately affected by
      HIV infection. Most non-B HIV subtypes were associated with overseas assignment.
      Given the increased frequency and length of assignments, and the expanding HIV
      genetic diversity observed in this population, there is a need for active HIV
      genotyping surveillance and a need to reinforce primary HIV prevention efforts.

PMID- 20673144
TI  - Bacterial contamination of surgical suture resembles a biofilm.
AB  - BACKGROUND: Although much attention is currently directed to studying microbial
      biofilms on a variety of surfaces, few studies are designed to study bacterial
      growth on surgical suture. The purpose of this study was to compare the kinetic
      development of Staphylococcus aureus and Enterococcus faecalis on five surgical
      suture materials and to clarify factors that might influence this growth.
      METHODS: Pure cultures of S. aureus and E. faecalis were incubated with five
      types of suture for four days using either tissue culture medium or a bacterial
      growth medium. Suture-associated bacteria were quantified daily. In selected
      experiments, the bacterial growth medium was supplemented with heparin, a
      substance known to promote S. aureus biofilm formation. The ultrastructure of S.
      aureus biofilm developing on braided suture was studied with scanning electron
      microscopy. RESULTS: Staphylococcus aureus and E. faecalis were recovered in
      greater numbers (typically p < 0.01) from braided than from monofilament suture,
      and the numbers of bacteria were greater (often p < 0.01) on sutures incubated in
      bacterial growth medium rather than tissue culture medium. Addition of heparin
      1,000 U/mL to silk or braided polyglactin 910 suture incubated three days with S.
      aureus resulted in greater numbers of bacteria on day one but not on subsequent
      days. Scanning electron microscopy showed a maturing S. aureus biofilm that
      developed from small clusters of cells among amorphous material and fibrillar
      elements to larger clusters of cells that appeared covered by more consolidated
      extracellular material. CONCLUSIONS: Bacterial growth was favored on braided vs.
      monofilament suture, and heparin enhanced bacterial adherence after day one, but
      not at subsequent times. Staphylococcus aureus adhered to suture material and
      formed a structure consistent with a bacterial biofilm.

PMID- 20673145
TI  - Postoperative outcomes associated with topical skin adhesives among women having
      hysterectomies.
AB  - BACKGROUND: Multiple options are available for closure of hysterectomy incisions.
      This study compared postoperative clinical and economic outcomes using topical
      skin adhesive (2-octyl cyanoacrylate; OCA) vs. conventional skin closure in women
      undergoing total abdominal hysterectomy. METHODS: A multi-hospital administrative
      database was used to identify women discharged in 2005 who had undergone total
      abdominal hysterectomy. Patients, classified by skin closure as suture (n =
      21,201), staples (n = 23,441), OCA (n = 880), or staples + OCA (n = 489), were
      compared on length of inpatient stay (LOS), total inpatient cost, and non
      prophylactic antibiotic treatment after day four. RESULTS: The unadjusted mean
      LOS was 3.9, 4.5, 3.7, and 5.2 days for suture, staples, OCA, and staples + OCA,
      respectively; and the percentages of patients having antibiotic treatment were
      12.93, 17.51, 11.14, and 23.72. There were overall differences in adjusted mean
      LOS, mean total cost, and antibiotic treatment (p < 0.0001). Pairwise comparisons
      indicated no difference between sutures and OCA, whereas the outcomes for each of
      the non-staple groups were more favorable than those for the staple group (p <
      0.01). Results were similar in adjusted comparisons, with pairwise comparisons
      between OCA and staples at or near the threshold for significance. CONCLUSIONS: 2
      octyl cyanoacrylate appears to be a safe and cost-effective alternative to
      topical sutures for patients having total abdominal hysterectomy. There were less
      favorable outcomes in groups receiving staples.

PMID- 20673146
TI  - Age-related changes in heart function by serial echocardiography in women aged 40
      80 years.
AB  - AIM: To determine if a defined set of echocardiographic parameters at entry and
      exit of a longitudinal study over 5 years showed changes with aging. METHODS: The
      cohort consisted of 484 randomly recruited women aged 40-80. They were examined
      by two echocardiography cardiologists, independent of the medical information for
      these women. RESULTS: Across the age decades (40-49, 50-59, 60-69, 70-79 years),
      body weight and body surface area (BSA) did not vary, and diastolic blood
      pressure (DBP) was stable; systolic blood pressure (SBP) progressively increased.
      There was gradual decline in left ventricular (LV) diastolic function, increase
      in LV muscle mass, and decrease in LV end-diastolic volume (LVEDV). The serial
      decrease in rate of change over 5 years in ejection fraction (ET) was small but
      significant across the four age decades. CONCLUSIONS: As expected, there were age
      related changes in cardiac structure and function over time in women who showed
      no apparent cardiovascular disease (CVD) at entry to the study. The direction of
      these serial changes was toward the development of LV stiffness and likelihood of
      subsequent heart failure. The clinical significance of the decrease in rate of
      change in EF remains unclear.

PMID- 20673147
TI  - Soy isoflavones and bone mineral density in perimenopausal and postmenopausal
      Western women: a systematic review and meta-analysis of randomized controlled
      trials.
AB  - BACKGROUND: Several randomized controlled trials (RCTs) have compared the effect
      of phytoestrogens (PEs) vs. placebos on bone density after menopause, with
      inconsistent results. METHODS: We performed a systematic review to assess the
      overall effect of PEs on bone mineral density (BMD) in menopausal Western women.
      We searched for all RCTs comparing PEs with placebos conducted on perimenopausal
      or postmenopausal Western women, published from January 1990 to February 2010.
      The main outcome measure was the lumbar spine (LS) BMD. RESULTS: We identified 17
      studies on soy isoflavone (IFs) bone-sparing effects. Some studies did not report
      a difference between treated and untreated women, whereas others supported a
      significant role of IFs on slowing bone loss, although these studies suffered
      from an internal lack of consistency, as a positive effect emerged in some bone
      districts but not in others. Data on LS BMD were available in 12 studies
      including 1433 subjects overall. The effect of PEs on BMD (mg/cm(2)) was not
      statistically significant (mean difference 9.86 mg/cm(2), 95% confidence interval
      [CI] -2.64-22.36) under a random-effects model. Excluding the genistein study,
      however, analyses of IF mixtures did not show a bone-sparing effect (0.73, 95% CI
      -2.79-4.25). No increasing effect emerged when dose and treatment duration were
      increased. CONCLUSIONS: Our review and meta-analysis suggest that IF mixtures are
      not effective in decreasing bone loss in perimenopausal and postmenopausal
      Western women. The role of isolated genistein and individual genetic capacity to
      metabolize IFs is still open to evaluation.

PMID- 20673148
TI  - Clavien classification of complications after the initial series of robot
      assisted radical prostatectomy: the Cancer Institute of New Jersey/Robert Wood
      Johnson Medical School experience.
AB  - PURPOSE: To study the safety and feasibility of robot-assisted radical
      prostatectomy (RARP) for the surgical management of localized prostate cancer, we
      analyzed perioperative parameters and the pattern of complications in our
      patients who underwent RARP. PATIENTS AND METHODS: After the performance of more
      than 600 RARP over a 4-year period by a single surgeon using the daVinci(r) robot
      system at the Cancer Institute of New Jersey/Robert Wood Johnson Medical School,
      we reviewed the medical records of the first 200 patients retrospectively. All
      patients were divided into four groups according to the order of case numbers to
      compare intergroup differences in preoperative characteristics and perioperative
      parameters. Perioperative complications were determined in all patients, and
      complications were classified according to the Clavien classification system.
      RESULTS: The mean operative time was 212 minutes, and the mean blood loss was 189
      mL. The mean length of hospital stay was 1.13 days. Overall, 12% (24 men)
      experienced various perioperative complications among the 200 patients. Of the
      total 24 patients, 5 (20.8%) men experienced intraoperative complications, and 19
      (79.2%) men showed postoperative complications. Rectal injury occurred in two
      (8.3%) men, and the injury was repaired primarily using two-layer suture
      techniques without any sequelae. Three (12.5%) patients had femoral neuropathy,
      and urinary retention developed in 7 (25.0%) patients. Among our 200 patients, no
      transfusion was needed intraoperatively and postoperatively. There were nine
      (4.5%) patients in the Clavien grade I complications category, and another 9
      (4.5%) men were classified as grade II complications. Six (3.0%) men had grade
      IIIb complications, and there were no grade IV or V complications. CONCLUSIONS:
      In our initial series of RARP procedures, we experienced low morbidity, with the
      overall complication rate of 12%. After implementing minor modifications, most of
      the early complications were prevented. Rectal injuries, if recognized
      intraoperatively, can be repaired primarily.

PMID- 20673149
TI  - Cutaneous tuberculosis: a diagnostic and therapeutic study of 20 cases.
AB  - Cutaneous tuberculosis is showing a resurgence. It continues to be one of the
      most elusive and difficult diseases to diagnose in dermatological practice. We
      sought to describe the clinical manifestations, laboratory features, and
      antituberculous therapy in cases of cutaneous tuberculosis. Twenty cases of
      cutaneous tuberculosis were observed in this study. Of the 20 cases, seven were
      in women (35%) and 13 were in men (65%). There were eight (40%) cases of lupus
      vulgaris, four (20%) cases of orificial tuberculosis, four (20%) cases of
      tuberculosis verrucosa cutis, two (10%) cases of scrofuloderma, and two (10%)
      cases of primary inoculation tuberculosis. In total, 20 strains of acid-fast
      bacilli were isolated by culture in Lowenstein-Jensen medium at 37 degrees C.
      Mycobacterial species identification by polymerase chain reaction (PCR) assay
      showed that all strains were Mycobacterium tuberculosis. In vitro susceptibility
      testing by use of absolute concentration method showed that the 20 strains were
      sensitive to rifampin, ethambutol, and isoniazid; however, two strains were
      resistant to streptomycin. All of the patients responded favourably to
      antituberculous treatment. Cutaneous tuberculosis is a skin disease that should
      still be thought much of in mainland China, and in this study lupus vulgaris is
      the most common clinical presentation.

PMID- 20673150
TI  - Hailey-Hailey disease: effective treatment with topical cadexomer iodine.
AB  - Hailey-Hailey disease (HHD) or familial benign pemphigus is known to have a
      chronic relapsing-remitting course. Conventional treatment with topical steroids
      and antibiotics often yield unsatisfactory results. We report a case of HHD
      treated successfully with topical cadexomer iodine powder. Cadexomer iodine may
      be a useful therapy for recalcitrant cases of HHD.

PMID- 20673151
TI  - Evaluation of optimal color for stent identification in a hemorrhagic
      environment.
AB  - INTRODUCTION: The endoscopic deployment and extraction of endoluminal stents,
      such as ureteral stents, is commonplace in contemporary medical management of
      many diseases. In a hemorrhagic environment, endoscopic identification of a stent
      can be challenging. To date, no study has evaluated the optimal color for
      endoscopic stent identification. METHODS: Eight different colored stents were
      placed in a simulated bladder model. Each stent color was evaluated in saline and
      three progressively more concentrated bloody environments. A flexible cystoscope
      was used to make 15-second video clips of the stents in each environment.
      Participants viewed the videos in a random sequence. Participants were asked to
      identify the color of each stent, and rate the identification on a 10-point
      scale. Logistic regression models were used to model the relationship between
      identification, stent color, environment, and experience. RESULTS: Forty-seven
      participants reviewed the videos. In clear and mildly bloody environments, blue
      stents had the highest identification (p < 0.06, p = 0.001, respectively). In
      moderately bloody environments, yellow stents had the highest identification (p <
      0.01), whereas silver stents had the highest identification in severely bloody
      settings (p = 0.004). Blue and green stents were identified most commonly and
      received the highest identification scores in all environments. Level of training
      and experience with endoscopy were not significantly associated with the correct
      response rate. CONCLUSIONS: This study demonstrates that the color of a stent
      plays an important role in endoscopic identification. Our results suggest that
      blue and green colors offer superior visibility in both clear and hemorrhagic
      environments.

PMID- 20673152
TI  - Acitretin revisited in the era of biologics.
AB  - Acitretin is a time-honored treatment for psoriasis. During the last decade
      biologics have revolutionized the treatment of psoriasis. This raises the
      question: What is the position of acitretin as a classical systemic treatment for
      psoriasis in the era of biologics? Based on the mode of action of acitretin, it
      is evident that at least one antipsoriatic treatment has to be available in the
      armamentarium of antipsoriatic treatments that is not immunosuppressive, intended
      for those patients who are contraindicated for immunosuppressive treatment. It is
      attractive to speculate that at least an additive or possibly a synergistic
      effect can be expected in case of combination of acitretin with a biologic. The
      efficacy of acitretin in chronic plaque psoriasis as a monotherapy is below
      methotrexate and cyclosporine. However, acitretin in combination with
      phototherapy has an efficacy at least comparable with the other classical
      systemic treatments. Based on several clinical studies it can be concluded that
      acitretin is an important treatment option in case of contraindications for
      immunosuppression, such as patients with infections or cancer-prone patients.
      Furthermore, some evidence is available for high efficacy of the combination of
      acitretin and biologics.

PMID- 20673153
TI  - The value of monitoring ciclosporin concentration 2 hours post-dose (C2) in
      dermatology: a prospective cohort study.
AB  - BACKGROUND: Ciclosporin (CsA) is an effective treatment for several inflammatory
      dermatoses, including psoriasis and eczema. In contrast to transplantation
      medicine, dermatologists do not routinely use CsA blood concentrations to guide
      therapy. OBJECTIVE: To determine the range of CsA levels at 2 hours after dosing
      (C2 levels) and whether these C2 levels had any relationship to clinically
      relevant parameters, such as CsA dose, serum creatinine, blood pressure, PASI
      (psoriasis area and severity index) or DLQI (dermatology life quality index).
      METHODS: A total of 18 patients on CsA maintenance therapy (cohort 1) and eight
      patients commencing on CsA (cohort 2) were included in the study. In cohort 1,
      CsA blood concentrations were measured at 2 hours post-dose on one occasion only,
      while in cohort 2, C2 levels were performed at baseline and at 4, 8 and 12 weeks
      after commencing CsA treatment. RESULTS: In cohort 1, a significant relationship
      between C2 levels and PASI was found. However, no relationship was found between
      C2 levels and CsA dose, blood pressure, or serum creatinine. In cohort 2, higher
      C2 levels were associated with lower PASI scores (p <0.05) and DLQI scores at 4
      weeks (p = 0.014). CONCLUSION: We suggest that C2 levels may be beneficial in
      patients who are not responding well to CsA treatment in the loading phase.

PMID- 20673154
TI  - Successful treatment of angiofibromata of tuberous sclerosis complex with
      rapamycin.
AB  - Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous syndrome
      manifesting as hamartomatous growths in multiple organs. We present two cases of
      patients with TSC and associated facial angiofibromata treated with topical and
      oral rapamycin and discuss the role for rapamycin in the treatment of these
      disfiguring lesions. Our patients demonstrated decreased numbers of
      angiofibromata and less redness with this treatment. This is the first published
      report on the use of topical rapamycin for the treatment of angiofibromata.

PMID- 20673155
TI  - Perioperative management of tumor necrosis factor antagonists in patients with
      psoriasis and other inflammatory disorders.
AB  - Tumor necrosis factor alpha (TNF-alpha) plays an important role in host defense
      and possibly wound healing. It is also linked to the pathophysiology of many
      inflammatory diseases, including psoriasis. The TNF antagonists are a class of
      agents that have proven effective in treating psoriasis and psoriatic arthritis,
      yet the immunosuppressive effects of these agents raise concern over their use
      perioperatively. Currently, there is no consensus as to when TNF antagonists
      should be discontinued prior to surgery. Furthermore, data on the topic are
      limited to inflammatory bowel disease (IBD) and rheumatoid arthritis (RA). This
      paper reviews the literature on post-surgical outcomes in patients with RA and
      IBD receiving anti-TNF therapy. Although most studies reveal no statistically
      significant increased risk of post-surgical complications in these patients, the
      retrospective design and small sample size of these studies limits
      interpretation. Furthermore, when applying these data to psoriasis and psoriatic
      arthritis, physicians must also consider disease severity, individual
      comorbidities, and the pharmacokinetics of the different TNF antagonists.
      Additional studies are needed in psoriasis and psoriatic arthritis in order to
      develop truly evidence-based dermatologic guidelines for perioperative management
      of the TNF antagonists.

PMID- 20673156
TI  - The weight of a finger-tip unit of ointment in 5-gram tubes.

PMID- 20673157
TI  - Severe pyoderma gangrenosum unresponsive to etanercept and adalimumab.
AB  - BACKGROUND: A 74-year-old female with severe and therapy-resistant pyoderma
      gangrenosum (PG) was treated for more than 40 years with topical antibacterial
      ointments, topical and systemic corticosteroids, dapsone and azathioprine.
      Generally, immunosuppression is the mainstay of treatment of PG, but in our
      patient cyclosporine had to be discontinued because of significant serious side
      effects. An attempt was made to decrease the amount of steroids, but tapering of
      the prednisone dose resulted in relapses of PG. OBSERVATION: Off-label use of
      etanercept resulted in a temporary limited clinical improvement. After 6 months,
      initial clinical improvement reduced and adalimumab was started. Unfortunately,
      after 6 months of adalimumab no clinical improvement was seen. Therefore,
      systemic corticosteroids had to be continued with very good clinical results.
      CONCLUSION: In concordance with previous results of several other studies,
      reviews and case reports, we presume that possibly both etanercept and adalimumab
      could be excellent therapeutic alternatives in the treatment of PG.
      Unfortunately, the effectiveness of both etanercept and adalimumab were very
      limited in our case. Literature research revealed no other successful studies on
      the off-label use of other immunomodulators as an alternative treatment option
      for PG. However, infliximab or ustekinumab could be alternative treatment
      options.

PMID- 20673158
TI  - Treatment of recalcitrant viral warts with pulsed dye laser MAL-PDT.
AB  - BACKGROUND: Photodynamic therapy (PDT) has been explored for the treatment of
      recalcitrant viral warts (VW) with good results in recent publications. METHODS:
      We carried out a descriptive and observational study in 19 patients with
      recalcitrant VW. Methyl aminolaevulinic acid (MAL) was occluded for 3 hours and
      pulsed dye laser (PDL) was used as the light source. VW were treated weekly until
      they were clear or for a maximum of six sessions. RESULTS: A total of 53% of the
      VW cleared, and 26% of the patients demonstrated complete clearance of all their
      VW. The treatment was well tolerated and no adverse events were recorded.
      CONCLUSIONS: PDL-PDT is an effective and well-tolerated treatment option for
      patients with recalcitrant VW. Though only half of patients show any improvement,
      responders are likely to show complete clearance of their warts.

PMID- 20673159
TI  - Do genetic variations in antioxidant enzymes influence the course of hereditary
      hemochromatosis?
AB  - Iron-induced oxidative stress promotes hepatic injury in hereditary
      hemochromatosis, which can be influenced by genetic traits affecting antioxidant
      enzymes. We assessed the influence of Ala16Val-superoxide dismutase 2, Pro198Leu
      glutathione peroxidase 1, and -463G/A-myeloperoxidase genotypes (high activity
      for the Ala, Pro, and G alleles, respectively) on the risks of cirrhosis and
      hepatocellular carcinoma (HCC) in patients homozygous for the C282Y
      hemochromatosis (HFE) gene mutation. Both the 2G-myeloperoxidase genotype and
      carriage of one or two copies of the Ala-superoxide dismutase 2 allele were more
      frequent in patients with cirrhosis or HCC. Patients cumulating these two genetic
      traits had higher rates of cirrhosis and HCC than other patients.

PMID- 20673161
TI  - The role of energy metabolism dysfunction and oxidative stress in schizophrenia
      revealed by proteomics.
AB  - Schizophrenia is a psychiatric illness that affects approximately 30 million
      people worldwide. Converging lines of evidence suggest that mitochondrial
      function may be compromised in this disorder, and this can lead to perturbations
      in calcium buffering, oxidative phosphorylation, increased production of reactive
      oxygen species, and apoptotic factors, which can, in turn, affect neuronal
      processes such as neurotransmitter synthesis and synaptic plasticity. Proteomics
      studies in brain and peripheral tissues of schizophrenia patients have provided
      considerable evidence and identified biomarker fingerprints corresponding to such
      pathways. Here we review the results of these studies with a focus on the
      biomarker pattern depicting alterations in energy metabolism and oxidative stress
      in this debilitating illness.

PMID- 20673160
TI  - Cockayne syndrome B protects against methamphetamine-enhanced oxidative DNA
      damage in murine fetal brain and postnatal neurodevelopmental deficits.
AB  - Methamphetamine (METH) increases the oxidative DNA lesion 8-oxoguanine (8-oxoG)
      in fetal mouse brain, and causes postnatal motor coordination deficits after in
      utero exposure. Like oxoguanine glycosylase 1 (OGG1), the Cockayne syndrome B
      (CSB) protein is involved in the repair of oxidatively damaged DNA, although its
      function is unclear. Here we used CSB-deficient Csb(m/m) knockout mice to
      investigate the developmental role of DNA oxidation and CSB in METH-initiated
      neurodevelopmental deficits. METH (40 mg/kg intraperitoneally) administration to
      pregnant Csb females on gestational day 17 increased 8-oxoG levels in Csb(m/m)
      fetal brains (p < 0.05). CSB modulated 8-oxoG levels independent of OGG1
      activity, as 8-oxoG incision activity in fetal nuclear extracts was identical in
      Csb(m/m) and Csb(+/+)mice. This CSB effect was evident despite 7.1-fold higher
      OGG1 activity in Csb(+/+) mice compared to outbred CD-1 mice. Female Csb(m/m)
      offspring exposed in utero to METH exhibited motor coordination deficits
      postnatally (p < 0.05). In utero METH exposure did not cause dopaminergic nerve
      terminal degeneration, in contrast to adult exposures. This is the first evidence
      that CSB protects the fetus from xenobiotic-enhanced DNA oxidation and postnatal
      functional deficits, suggesting that oxidatively damaged DNA is developmentally
      pathogenic, and that fetal CSB activity may modulate the risk of reactive oxygen
      species-mediated adverse developmental outcomes.

PMID- 20673163
TI  - Differential dependence on cysteine from transsulfuration versus transport during
      T cell activation.
AB  - The synthesis of glutathione, a major cellular antioxidant with a critical role
      in T cell proliferation, is limited by cysteine. In this study, we evaluated the
      contributions of the x(C)(-) cystine transporter and the transsulfuration pathway
      to cysteine provision for glutathione synthesis and antioxidant defense in naive
      versus activated T cells and in the immortalized T lymphocyte cell line, Jurkat.
      We show that the x(C)(-) transporter, although absent in naive T cells, is
      induced after activation, releasing T cells from their cysteine dependence on
      antigen-presenting cells. We also demonstrate the existence of an intact
      transsulfuration pathway in naive and activated T cells and in Jurkat cells. The
      flux through the transsulfuration pathway increases in primary but not in
      transformed T cells in response to oxidative challenge by peroxide. Inhibition of
      the transsulfuration pathway in both primary and transformed T cells decreases
      cell viability under oxidative-stress conditions.

PMID- 20673162
TI  - DAF-16/Forkhead box O transcription factor: many paths to a single Fork(head) in
      the road.
AB  - The Caenorhabditis elegans Forkhead box O transcription factor (FOXO) homolog DAF
      16 functions as a central mediator of multiple biological processes such as
      longevity, development, fat storage, stress resistance, and reproduction. In C.
      elegans, similar to other systems, DAF-16 functions as the downstream target of a
      conserved, well-characterized insulin/insulin-like growth factor (IGF)-1
      signaling pathway. This cascade is comprised of an insulin/IGF-1 receptor, which
      signals through a conserved PI 3-kinase/AKT pathway that ultimately downregulates
      DAF-16/FOXO activity. Importantly, studies have shown that multiple pathways
      intersect with the insulin/IGF-1 signaling pathway and impinge on DAF-16 for
      their regulation. Therefore, in C. elegans, the single FOXO family member, DAF
      16, integrates signals from several pathways and then regulates its many
      downstream target genes.

PMID- 20673164
TI  - Genetic association studies of antioxidant pathway genes and schizophrenia.
AB  - The endogenous production of highly reactive oxidation species is an inherent by
      product of cellular energy metabolism. Cellular antioxidant defense systems
      (AODS) comprising various antioxidants counter these damaging effects. Several
      lines of evidence, including postmortem studies, suggest increased oxidative
      stress in patients with schizophrenia. Some genetic association studies and gene
      expression studies suggest that patients also may have altered ability to mount
      antioxidative mechanisms. As the genetic associations may provide etiologic
      evidence in support of the oxidative-stress hypothesis of schizophrenia, a
      focused review has been conducted. We also suggest avenues for further research.

PMID- 20673165
TI  - CALU A29809G polymorphism in coronary atherothrombosis: Implications for coronary
      calcification and prognosis.
AB  - INTRODUCTION: Arterial calcification is a risk factor for atherosclerosis.
      Calumenin (CALU), a protein regulating proteins involved in coagulation and
      arterial calcification also has extracellular functions related to
      atherosclerosis. We recently described that CALU polymorphism A29809G was related
      to acenocoumarol requirements, and we wanted to evaluate its role in arterial
      calcification and prognosis. PATIENTS AND METHODS: A total of 374 consecutive
      patients with non-ST-elevation acute coronary syndrome (nSTACS). In 175 of them,
      who underwent percutaneous coronary intervention, we assessed calcification in
      each main coronary artery. Follow-up at 1 and 6 months was performed for adverse
      end-points. RESULTS: CALU 29809G carriers were more frequent in the low calcium
      group (P = 0.037). The presence of >or=3 cardiovascular risk factors and CALU
      polymorphism were associated with arterial calcification (OR 2.34, P = 0.049; and
      OR 0.34, P = 0.019, respectively). CALU 29809G allele was the only variable
      associated with events at 1 month (HR 0.42; P = 0.042). Multivariate analysis
      showed that, at 6 months, age and severe anginal symptoms were associated with
      worse prognosis (HR 2.13, P = 0.023; and HR 2.01, P = 0.011, respectively),
      whereas CALU 29809G allele associated with good prognosis (HR 0.59, P = 0.044).
      Our results suggest that CALU A29809G is associated with arterial calcification
      and short-term prognosis of the outcome of patients with nSTACS.

PMID- 20673166
TI  - Service use and barriers to care among heroin users: results from a national
      survey.
AB  - BACKGROUND: Heroin use is associated with many serious consequences.While
      effective treatments exist, barriers to services persist. Understanding service
      use and barriers to treatment can structure treatment practice and target
      interventions for those who are most at risk. OBJECTIVES: To describe patterns
      and correlates of substance abuse service utilization and treatment barriers
      among a nationally representative sample of heroin users. METHODS: Data for this
      study were derived from the National Epidemiologic Survey on Alcohol and Related
      Conditions. This study focused on lifetime heroin users (N = 150). RESULTS: Fifty
      nine percent of heroin users reported receiving at least one treatment service.
      The most common services used were 12-step programs, detoxification, and
      rehabilitation. Approximately 44% reported at least one barrier to treatment. The
      most common were lack of motivation and beliefs that it could be managed alone.
      In a multivariate logistic regression, having a heroin use disorder was
      associated with a greater likelihood of receiving services (OR = 6.09) and
      experiencing a barrier (OR = 11.11) compared to those without a disorder.
      CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: High rates of service use and barriers
      were observed for all levels of heroin involvement. These findings underscore the
      importance of improving access to services for this group, even when full
      criteria for a drug disorder is not met. Integration of motivational approaches
      is also needed within the most common services used. To our knowledge, this is
      the first study to describe patterns and correlates of service use using a
      nationally representative community sample of heroin users.

PMID- 20673167
TI  - Treatment patterns in patients with acute coronary syndrome undergoing
      percutaneous coronary intervention.
AB  - BACKGROUND: The Antiplatelet Therapy Observational Registry (APTOR) is a
      prospective observational study of acute coronary syndrome (ACS) patients
      undergoing percutaneous coronary intervention (PCI) in a 'real world' clinical
      setting. Here the authors report on the management of ACS patients in three
      European countries during the hospital phase and through 12-months' follow-up,
      including use of antiplatelet agents, co-medications and stents, as well as
      clinical outcomes at 12 months. METHODS: ACS patients undergoing PCI (N = 1525)
      from January to August 2007 were planned to be consecutively recruited in France,
      Spain and the UK. RESULTS: Index diagnosis was unstable angina/non-ST-segment
      elevation myocardial infarction (MI) in 62% and ST-segment elevation MI in 38%.
      Prior to the index ACS event, 17% were prescribed both aspirin and clopidogrel.
      While in-hospital clopidogrel and aspirin use was similar across countries,
      considerable variation was observed between countries at 12 months (clopidogrel
      66-75%; aspirin 86-95%). The UK most frequently used a 300-mg clopidogrel loading
      dose (70%) compared with France (53%) and Spain (56%), while >300 mg was used in
      21%, 34% and 16% patients, respectively. Bare metal stents only were used in 42%
      of subjects, drug-eluting stents (DES) only in 40%, and both in 10%, with the
      highest rates of DES use in Spain (70%) followed by the UK (47%) and France
      (31%). The composite endpoint of cardiovascular (CV) death, MI or stroke occurred
      in 4.7% of patients by 12 months. CONCLUSIONS: APTOR shows marked variation in
      ACS management between countries in antiplatelet therapy, co-medications and
      stent use. Due to the observational design of the registry, statistical testing
      was not applied and data should be seen as hypothesis generating. These data
      provide a useful benchmark for comparison with current guidelines.

PMID- 20673169
TI  - SCLM, total saponins extracted from Chaihu-jia-longgu-muli-tang, reduces chronic
      mild stress-induced apoptosis in the hippocampus in mice.
AB  - Increasing evidence demonstrates that stress or depression can lead to atrophy
      and cell loss in the hippocampus. In contrast, antidepressant treatment
      significantly reduces apoptosis in the dentate granule cell layer and subgranular
      zone in animal models of depression. In the present study, we investigated the
      neuroprotective action of SCLM, the total saponins extracted from Chaihu-jia
      longgu-muli-tang, a traditional Chinese medicinal formula which was prescribed
      1000 years ago, in the reduction of apoptosis in hippocampal neurons using an
      experimental chronic mild stress (CMS) model. Mice were subjected to the CMS
      procedure for a period of 21 consecutive days. SCLM (100 mg/kg, p.o.) or
      fluoxetine (20 mg/ kg, p.o.) was administered during the stress periods. CMS mice
      showed a decreased sucrose intake over 21 days, and an increase in the number of
      TUNEL-positive neurons as well as up-regulation of the apoptotic-related factors,
      such as Bax and caspase-3 in the hippocampus, compared with control mice. On the
      other hand, the administration of SCLM (100 mg/kg) and fluoxetine (20 mg/kg)
      reversed these effects induced by CMS, showing a significant increase of sucrose
      intake and a dramatic reduction of TUNEL-positive neurons and decreased
      expression of Bax and caspase-3 proteins. The present results suggest that SCLM
      possesses a significant antidepressant-like property, and this effect may be
      through protection against stress-induced neuronal apoptosis by affecting the
      expression of Bax and caspase-3 proteins in the hippocampus. These findings
      provide important information that the anti-apoptotic effect of herbal medicine
      therapy may be beneficial for the treatment of depression.

PMID- 20673170
TI  - Toxicological assessments of aqueous extract of Eugenia jambolana stem bark.
AB  - Eugenia jambolana Lam. (Myrtaceae) is widely used in folk medicine as an
      antidiabetic, but there is a lack of information about its toxicity, especially
      for the stem bark. The present study evaluated acute oral and repeated-dose
      toxicity of the stem bark aqueous extract of Eugenia jambolana (EJ) in albino
      mice and Wistar rats. In the acute toxicity tests, mice received oral doses of EJ
      extract as 300, 2000, and 5000 mg/kg body weight. Mortality, signs of toxicity,
      body weight, food consumption, and gross findings were observed for 14 days post
      treatment. In repeated toxicity, rats were orally treated with 300, 1000, and
      2000 mg/kg body weight, and animals were observed till the 28th day of treatment.
      At the end of the study period, surviving animals were fasted overnight and
      anesthetized for blood collection and removal of some vital organs for
      histopathology. No significant differences were noted in body and organ weights
      between the control and treated groups from either of the studies. In addition,
      hematological parameters, e.g., red blood cell count (RBC), hemoglobin
      concentration (Hb), mean corpuscular hemoglobin concentration (MCHC), platelets
      (PLT), and white blood cell differential count, biochemical parameters, e.g.,
      blood glucose, creatinine, blood urea nitrogen (BUN), alkaline phosphatase (ALP),
      bilirubin, total protein, and albumin, and ions, e.g., potassium, sodium,
      chloride, calcium, and phosphorus, were studied in the repeated-dose toxicity
      study. In conclusion, these investigations indicate the safety of acute and
      repeated oral administration of the aqueous extract of EJ stem bark, suggesting
      therefore that it may be continuously used safely.

PMID- 20673171
TI  - Free radical scavenging and tyrosinase inhibition activity of oils and sericin
      extracted from Thai native silkworms (Bombyx mori).
AB  - Oils and sericin were extracted from pupae and silk cocoons, respectively, of the
      five Thai native silkworms (Bombyx mori, Linnaeus (Bombycidae)), namely,
      Keawsakol, Nangnoi, Somrong, Nangleung, and Noneruesee, which are variations of
      the same species. The oils were extracted by a hot process using Soxhlet
      apparatus and a cold process using petroleum ether, while sericin was extracted
      by basic hydrolysis and autoclaving. Sericin from the five Thai native silkworms
      showed free radical scavenging activity lower than the standard antioxidants
      (vitamin C, vitamin E, and BHT) by about 20-100-fold, but all oils gave higher
      activity than that of the standard linoleic acid by 11-22-fold. Oil extracted
      from Noneruesee by the cold process gave the highest DPPH scavenging activity,
      compared with other oil samples. All sericin samples showed tyrosinase inhibition
      activity with IC(50) values in the range of 1.2-18.76 mg/mL, but only oils from
      Noneruesee extracted by the hot process, and Nangleung, Somrong, and Noneruesee
      extracted by the cold process, showed this activity. Oil extracted by the hot
      process and sericin by basic hydrolysis from Noneruesee gave the highest
      tyrosinase inhibition activity, but lower than that of the standards vitamin C
      and kojic acid by 20-49 and 3-8 times, respectively. This study has suggested
      that sericin and oil from Noneruesee extracted by basic hydrolysis and the cold
      process, which gave the highest tyrosinase inhibition and free radical scavenging
      activity, respectively, can be applied in antiaging and whitening cosmetic
      products.

PMID- 20673172
TI  - Antinociceptive and anti-inflammatory effects of the ethanol extract of Alpinia
      conchigera rhizomes in various animal models.
AB  - Alpinia conchigera Griff. (Zingiberaceae), locally known to the Malays as
      "lengkuas ranting", is native to Peninsular Malaysia. The Malays traditionally
      used it to treat infection and rashes, and as a health drink. This study
      evaluated the analgesic and anti-inflammatory activities of the ethanol extract
      of A. conchigera rhizomes in mice and rats, respectively. The analgesic activity
      was elucidated using the acetic acid-induced writhing test, hot plate test, and
      formalin test, while the anti-inflammatory activity was determined using
      carrageenan-induced paw edema. The extract (30, 100, and 300 mg/kg) given
      intraperitoneally (i.p.) exhibited antinociceptive and anti-inflammatory
      activities in all tests used. The range of percentage of analgesia obtained for
      all doses of extract in the writhing test was 50-92%, and in the early and late
      phases of the formalin test was 25-62% and 63-98%, respectively. In addition,
      naloxone (5 mg/kg) given subcutaneously (s.c.) was found to reverse the extract
      (300 mg/kg)-induced antinociceptive activity in the writhing, hot plate, and
      formalin tests. Based on the results obtained, it can be concluded that the
      ethanol extract of A. conchigera rhizomes possessed a peripheral and central
      antinociceptive activity that was mediated, in part, via the opioid receptor, as
      well as anti-inflammatory activity.

PMID- 20673173
TI  - Antiulcer activity of ethanol leaf extract of Cassia fistula.
AB  - The ethanol leaf extract (ELE) of Cassia fistula Linn. (Caesalpinaceae) was
      evaluated for antiulcer activity against pylorus ligation-induced gastric ulcer.
      Ranitidine (30 mg/kg b.w.) and ELE at doses of 250, 500, and 750 mg/kg b.w. were
      administered orally in different groups of rats (n = 6), 1 h prior to pyloric
      ligation. Four hours after pyloric ligation, the gastric juice was collected for
      evaluation of various parameters. The antiulcer activity of ELE was evidenced by
      the significant attenuation of gastric volume, pH, free acidity, and total
      acidity in the gastric juice of pyloric-ligated rats in a dose-dependent manner,
      and this protective effect could be due to strengthening of the mucosal defense
      mechanism. ELE pre-treatment significantly attenuated the fall in status of
      sialic acid and fucose accompanied by an increase in hexose, hexosamine, total
      non-amino polysaccharide, total carbohydrate, and C:P ratio in the gastric juice
      of pylorus-ligated rats, and this effect could be due to protection of the
      mucosal barrier system. ELE pre-treatment significantly prevented the increase in
      LPO and SOD accompanied by a fall in CAT, in the gastric juice of pyloric-ligated
      rats. This protective ability of ELE against pylorus ligation-induced gastric
      ulcer could be attributed to its free radical scavenging and antioxidant
      properties. Higher doses of ELE (750 mg/kg b.w.) produced maximum antiulcer
      activity comparable to ranitidine treatment. In essence, the antiulcer activity
      of ELE could be attributed to (i) a decrease in gastric acid secretion, (ii)
      protection of the mucosal barrier and restoration of mucosal secretions, (iii)
      inhibition of free radical generation or prevention of lipid peroxidation, and
      (iv) free radical scavenging or antioxidant properties.

PMID- 20673174
TI  - Antimycobacterial activity of Indigofera suffruticosa with activation potential
      of the innate immune system.
AB  - Mycobacterium tuberculosis is responsible for over 8 million cases of
      tuberculosis (TB) annually. Natural products may play important roles in the
      chemotherapy of TB. The antimycobacterial activity and the innate immune response
      of methanol (METH) and dichloromethane (DCM) extracts of Indigofera suffruticosa
      Miller (Fabaceae) were evaluated. We observed that the minimum inhibitory
      concentrations (MICs) for METH and DCM extracts were 125 and 1000 microg/mL,
      respectively. However, they were able to induce the innate immune response
      through the production of high levels of NO and TNF-alpha (p < 0.001) by
      peritoneal exudate cells (PECs). These results suggest that I. suffruticosa
      extracts may have an important immunological role in the control of TB once
      macrophage activity is induced by them.

PMID- 20673175
TI  - Oligomer procyanidins from grape seeds induce a paraptosis-like programmed cell
      death in human glioblastoma U-87 cells.
AB  - CONTEXT: We recently reported that F2, an oligomer procyanidin fraction isolated
      from grape seeds, triggered an original form of cell death in U-87 human
      glioblastoma cells with a phenotype resembling morphological characteristics of
      paraptosis. However, the specific death mode induced by F2 and the mechanism of
      its action have not been assessed so far. OBJECTIVE: In the present work, we
      therefore further investigated the death mode of human glioblastoma cells induced
      by F2 and gained insight into the nature of the signaling pathways activated by
      F2 in glioblastoma cells. MATERIALS AND METHODS: Cell viability assay using MTT,
      (AO/EB) double staining, Western blot analysis, and Ca2+ assay using fura-2.
      RESULTS: Morphology studies revealed extensive cytoplasmic vacuolization in dying
      cells and no apoptotic body formation, membrane bleb formation, or nuclear
      fragmentation, though some was accompanied by MAPK activation and new protein
      synthesis, and was independent of caspase activation. Moreover, we demonstrated
      the involvement of calcium mobilization in F2-induced U-87 cell signaling.
      DISCUSSION AND CONCLUSION: Altogether we showed that F2 induced a kind of cell
      death resembling paraptosis in U-87 cells. The current report complements
      previous studies on the characterization of F2-induced U-87 cell death, enhances
      our understanding of the action mechanism of F2 on glioma, and helps in the
      development of novel antitumor therapeutics.

PMID- 20673176
TI  - Scorpion antivenom effect of micropropagated Aristolochia elegans.
AB  - Aristolochia elegans Mast. (Aristolochiaceae) has been used to treat scorpion
      envenoming in Mexican traditional medicine. In vitro studies of the
      pharmacological activity of raw extracts from A. elegans roots have shown
      activity against scorpion bite. The aim of the present study was to determine for
      the first time the antagonistic effect of hexane and methanol extracts of the
      aerial parts and roots from micropropagated A. elegans plants in a model of
      isolated guinea-pig ileum contracted by scorpion bite. Results showed that the
      methanol extracts of aerial organs (74%) and roots (65%) of micropropagated
      plants have a similar antitoxin activity against scorpion poisoning to hexane
      extracts of wild plants (65%). These results suggest that using methanol extracts
      from the micropropagated plant material instead of wild plant root extracts from
      A. elegans is an alternative for treatment against scorpion bite symptoms, and
      will contribute to the conservation of this medicinal species.

PMID- 20673177
TI  - Anti-inflammatory and antioxidant activities of Jungia paniculata.
AB  - The present study was conducted to evaluate the antioxidant and anti-inflammatory
      activities of Jungia paniculata (DC.) A. Gray (Asteraceae), used traditionally in
      Peru. The dry leaves were extracted with methanol, 50% methanol, and water. The
      anti-inflammatory activity of this plant was studied using in vitro (nitric oxide
      production in RAW 264.7 macrophages and sPLA(2) inhibition assay) and in vivo
      (carrageenan-induced paw edema in rats and TPA-induced ear edema in mice) model
      systems. The antioxidant activity of extracts was studied using three in vitro
      model systems (DPPH(*) radical-scavenging assay, ABTS(*+) assay, and superoxide
      radical-scavenging activity). The results have been correlated with total
      phenolics and total flavonoids contents. In the NO test of the extracts of Jungia
      paniculata, no significant cytotoxicities were observed at the concentrations
      determined by MTT assay. Only the MeOH50 extract of Jungia paniculata
      significantly inhibited PLA(2) enzyme activity (82.3 +/- 2.6%). At 3 h, the 50%
      methanol extract of Jungia paniculata at an oral dose of 500 mg/kg showed
      significant suppression of carrageenan-induced rat paw edema (36.36%). The same
      extract induced a 93.99% reduction in TPA-induced edema in topical
      administration. The extracts exhibited a high antioxidant activity and contained
      high total levels of polyphenols and flavonoids. There was a significant linear
      correlation between total phenolics and flavonoids contents and antioxidant
      activity in the three models used. In conclusion, Jungia paniculata possesses
      anti-inflammatory and antioxidant properties, which confirm the use of this plant
      in folk medicine as a topical anti-inflammatory herbal.

PMID- 20673178
TI  - Essential oil composition and variability of Hypericum perforatum from wild
      populations of northern Turkey.
AB  - CONTEXT: Hypericum perforatum L. (Guttiferae) contains many bioactive secondary
      metabolites including hypericins, hyperforins, and essential oil. OBJECTIVE: The
      present study was conducted to determine the variation in composition of
      essential oil in H. perforatum accessions from Turkey. MATERIAL AND METHODS: At
      full flowering, aerial parts of 30 plants were collected from 10 sites of
      northern Turkey and assayed for essential oil components by GC-FID and GC-MS.
      RESULTS: The chemical analysis revealed that the main constituents of the all
      analyzed samples were hydrocarbon and oxygenated sesquiterpenes such as beta
      caryophyllene (4.08-5.93%), gamma-muurolene (5.00-9.56%), beta-selinene (5.08
      19.63%), alpha-selinene (4.12-10.42%), d-cadinene (3.02-4.94%), spathulenol (2.34
      5.14%), and caryophyllene oxide (6.01-12.18%). Monoterpenes, both hydrocarbon and
      oxygenated, were represented by scarce amounts of alpha- and beta-pinene,
      myrcene, linalool, cis- and trans-linalool oxide, and alpha-terpineol. Principal
      component analysis was also carried out and, according to the results, the first
      nine principal components were found to represent 100% of the observed variation.
      DISCUSSION: The chemical variation among the populations is discussed as the
      possible result of different genetic and environmental factors. CONCLUSIONS: The
      wild populations examined here are potentially important sources for breeding and
      improvement of the cultivated varieties.

PMID- 20673179
TI  - Antihyperlipidemic activity of Clitoria ternatea and Vigna mungo in rats.
AB  - CONTEXT: Hyperlipidemia is one of the major risk factors for atherosclerosis and
      cardiovascular diseases. Some plants are effective in controlling hyperlipidemia.
      OBJECTIVE: To investigate the anti-hyperlipidemic effect of Clitoria ternatea L.
      and Vigna mungo L. (Fabaceae) on experimentally induced hyperlipidemia in rats.
      MATERIALS AND METHODS: The poloxamer 407-induced acute hyperlipidemia and diet
      induced hyperlipidemia models were used for this investigation. RESULTS: Oral
      administration of the hydroalcoholic extract of the roots and seeds of C.
      ternatea and the hydroalcoholic extract of the seeds of V. mungo resulted in a
      significant (p < 0.05) reduction of serum total cholesterol, triglycerides, very
      low-density lipoprotein cholesterol, and low-density lipoprotein cholesterol
      levels. The atherogenic index and the HDL/LDL ratio were also normalized after
      treatment in diet-induced hyperlipidemic rats. The effects were compared with
      atorvastatin (50 mg/kg, p.o.) and gemfibrozil (50 mg/kg, p.o.), reference
      standards. DISCUSSION: The cholesterol-lowering effect of C. ternatea might be
      attributed to increased biliary excretion and decreased absorption of dietary
      cholesterol. The cholesterol-lowering effects of V. mungo seeds might be because
      of decreased HMG-CoA reductase activity, increased biliary excretion, and
      decreased absorption of dietary cholesterol. Additionally, they improved natural
      antioxidant defense mechanisms. CONCLUSION: The findings of the investigation
      suggest that C. ternatea and V. mungo have significant antihyperlipidemic action
      against experimentally-induced hyperlipidemia.

PMID- 20673180
TI  - Effects of hawthorn seed and pulp extracts on the central nervous system.
AB  - CONTEXT: Investigating potential central nervous system (CNS) activities of
      Crataegus monogyna Jacq. (Rosaceae), hawthorn, fruit extracts. OBJECTIVE:
      Evaluating CNS effects and analgesic activities of hawthorn fruit extracts based
      on the traditional uses of the plant for neurosedative and pain killer actions.
      MATERIALS AND METHODS: Effects of hawthorn pulp (HPE) and seed extracts (HSE) at
      the dose range of 1-1000 mg/kg were examined on anxiety level, spontaneous
      locomotor activity, motor coordination, and nociceptive perception of mice.
      Morphine was used as a reference drug. RESULTS: HPE (100-1000 mg/kg) and HSE (10
      1000 mg/kg) significantly decreased not only the exploratory behaviors in hole
      board experiments, but also the spontaneous locomotor activities in activity cage
      tests. The same doses of extracts were found to be ineffective in Rota-Rod tests
      of mice. In tail-clip, hot-plate, and acetic acid-induced writhing tests, quite
      potent and dose-dependent analgesic activities were seen at 100-1000 mg/kg doses
      of HPE and 10-1000 mg/kg doses of HSE. Analgesic effects observed in all
      analgesia tests were antagonized by naloxone. DISCUSSION: Significant and dose
      dependent decreases in spontaneous locomotor activities and exploratory behaviors
      of animals suggested CNS depressant activities of both extracts. Complete
      naloxone antagonism in all applied analgesia tests indicated opioid-related
      analgesic activities of both extracts. CONCLUSION: These findings seem to support
      the traditional use of this plant to treat stress, nervousness, sleep disorders,
      and pain control.

PMID- 20673181
TI  - Cell proliferative effect of polyxyloses extracted from the rhizomes of wild
      turmeric, Curcuma aromatica.
AB  - Hot water-soluble crude polysaccharides were extracted from the rhizomes of wild
      turmeric, Curcuma aromatica Salisb. (Zingiberaceae), using dry grinding, boiling
      water extraction, and then ethanol precipitation. The crude polysaccharide
      extract was then fractionated by DEAE-cellulose ion exchange column
      chromatography, and subsequently further purified by Superdex G-200 gel
      filtration column chromatography, giving two relatively abundant polysaccharide
      fractions, called P11 and P21, and a much less common fraction P22 obtained in
      insufficient amounts for further analysis. The two main polysaccharide fractions
      were evaluated for monosaccharide composition by acid hydrolysis and high
      performance liquid chromatography (HPLC), whilst the molecular weight and
      functional groups were determined by gel permeable chromatography (GPC) and FT
      IR, respectively. Fractions P11 and P21 were found to be polyxyloses with
      molecular weight-averages of 469,171 and 157,665 Da, respectively. P11 (100
      microg/mL) could significantly induce human gingival fibroblast cells
      proliferation by 30%, while P21 (100 microg/mL) could significantly inhibit
      gingival fibroblast cells proliferation by 92%. The in vitro human primary
      gingival fibroblast cell proliferation in cell culture at a concentration of 100
      microg/mL.

PMID- 20673182
TI  - Inhibitory effect of PMC, a potent hydrophilic alpha-tocopherol derivative, on
      vascular smooth muscle cell proliferation: the pivotal role of PKC-alpha
      translocation.
AB  - CONTENT: Vascular smooth muscle cells (VSMCs) play a major role in the
      pathogenesis of atherosclerosis and restenosis, and thus the excessive
      proliferation of VSMCs contributes to neointimal thickening during
      atherosclerosis and restenosis. PMC (2,2,5,7,8-pentamethyl-6-hydroxychromane) is
      the most potent hydrophilic derivative of the alpha-tocopherols; it acts as a
      potent anti-inflammatory and free-radical scavenger. OBJECTIVE: The present study
      was designed to examine the inhibitory mechanisms of PMC in VSMC proliferation.
      MATERIALS AND METHODS: VSMC proliferation and cytotoxicity were measured by MTT
      and LDH assays, respectively. The cell cycle and translocation of PKC-alpha in
      VSMCs were used by flow cytometry and confocal microscope, respectively. To
      detect PKC-alpha translocation and activation in VSMCs, immunoblotting was
      performed in the present study. RESULTS: In this study, we demonstrate an anti
      proliferative effect of PMC in VSMCs. Concentration-dependent inhibition of serum
      induced VSMC proliferation was observed in PMC (20 and 50 muM)-treated cells. PMC
      pretreatment also arrested VSMC cell cycle progression at the G2/M phase.
      Furthermore, PMC exhibited obvious inhibitory effects on phorbol 12-myristate 13
      acetate (PMA)-induced protein kinase C (PKC)-alpha translocation and phospho
      (Ser/Thr) substrate phosphorylation. DISCUSSION AND CONCLUSION: The inhibitory
      mechanisms of PMC on VSMC proliferation is mediated, at least in part, by
      inhibition of PKC-alpha translocation and causes cell cycle arrest in the G2/M
      phase. PMC treatment may represent a novel approach for lowering the risk of or
      improving function in abnormal VSMC proliferation-related vascular diseases.

PMID- 20673183
TI  - The effect of CYP2C19 activity on pharmacokinetics of lansoprazole and its active
      metabolites in healthy subjects.
AB  - CONTEXT: Lansoprazole is a gastric proton-pump inhibitor and has been
      demonstrated to be effective in the treatment of various peptic diseases. The
      effects of CYP2C19 activity on the pharmacokinetics of lansoprazole and its
      active metabolites in Chinese subjects have not previously been evaluated.
      OBJECTIVE: The study aimed to evaluate the effects of CYP2C19 activity in healthy
      Chinese volunteers. MATERIALS AND METHODS: Twenty-two healthy volunteers were
      recruited for an open trial and received a single dose of 30 mg lansoprazole.
      Using a validated LC-MS/MS method, we measured the plasma concentrations of
      lansoprazole, 5-hydroxylansoprazole, and lansoprazole sulfone. The genotype of
      CYP2C19 was identified by polymerase chain reaction (PCR) analysis of single
      nucleotide polymorphisms (SNPs). Subjects were genotypically classified into the
      following three groups on the basis of PCR-SNP analysis for CYP2C19: homozygous
      EM (hmEM) group, heterozygous EM (htEM) group, and PM group. To test differences
      in pharmacokinetic parameters among the three groups, analysis of variance
      (ANOVA) after log-transformation of data was used. RESULTS AND CONCLUSION: Our
      results indicated that there were significant differences (p < 0.001) between the
      hmEM and PM groups, between the htEM and PM groups, and between the hmEM and htEM
      groups in C(max), AUC(0-t), and AUC(0-inf) of lansoprazole and lansoprazole
      sulfone. There were also significant differences (p < 0.001) between the hmEM and
      PM groups, and between the htEM and PM groups in C(max) of 5-hydroxylansoprazole.

PMID- 20673184
TI  - Semen Hoveniae extract protects against acute alcohol-induced liver injury in
      mice.
AB  - The protective effects of Semen Hoveniae extract (SHE) from Hovenia dulcis Thunb.
      (Rhamnaceae) on acute alcohol-induced liver injury were investigated in vivo
      using mice as test models. In the present study, SHE (150, 300, 600 mg/kg/day)
      was given to mice by intragastric administration for 4 days. Mice were gavaged
      with 60% ethanol 10 mL/kg after the last dose of extract. Six hours after alcohol
      administration, liver injury was evaluated by biochemical examination. Lipid
      peroxidation and the activity of antioxidants were measured by spectrophotometric
      methods. In mice, administration of SHE significantly decreased the activities of
      alanine aminotransferase (ALT) and aspartate transaminase (AST) in serum.
      Administration of SHE also protected against alcohol-induced alcohol
      dehydrogenase (ADH) elevation in mice. Concurrently, there was an augmentation in
      the activities of antioxidant enzymes such as superoxide dismutase (SOD),
      glutathione S-transferase (GST), and glutathione (GSH), and it also facilitated
      alcohol metabolism. Acute toxicity tests showed that a single dose of oral SHE up
      to 22 g/kg did not result in any death or toxic side effects in mice during 14
      days' observation. These results demonstrate that SHE could protect against acute
      alcohol-induced liver injury without any toxic side effects. Therefore, Semen
      Hoveniae has potential for the development of a clinically useful agent which
      could protect the liver from alcohol-induced injury.

PMID- 20673185
TI  - Targeting annexin A4 to counteract chemoresistance in clear cell carcinoma of the
      ovary.
AB  - IMPORTANCE OF THE FIELD: Epithelial ovarian cancer (EOC) is the leading cause of
      death from gynecological malignancies in Western countries. Among the four major
      histological subtypes of EOC, clear cell carcinoma (CCC) of the ovary is highly
      resistant to platinum-based chemotherapy and is consequently associated with poor
      patient prognosis in advanced stages. AREAS COVERED IN THIS REVIEW: An overview
      of the clinical characteristics of ovarian CCC; the role of annexin family
      proteins in tumor development and progression; the role of annexin A4 in
      enhancing cellular drug resistance; recent studies linking annexin A4
      overexpression to chemoresistance in tumors of ovarian CCC. WHAT THE READER WILL
      GAIN: Insight into the emerging role for annexin A4 in enhancing chemoresistance
      in ovarian CCC. TAKE HOME MESSAGE: Annexin A4 enhances cancer cell
      chemoresistance and is overexpressed in tumors of patients with ovarian CCC.
      Targeting of annexin A4 may represent a future strategy to counteract resistance
      to chemotherapy in ovarian CCC.

PMID- 20673187
TI  - Anti-complement activity of essential oils from red and black rice bran.
AB  - The volatile essential oils from red and black rice bran were obtained by
      hydrodistillation using a clevenger-type apparatus, and the components of that
      oil were analyzed by capillary gas chromatography-mass spectroscopy (GC-MS). The
      present study involved characterizing the chemical compositions, their amounts
      and the anti-complement activities of red and black rice bran. The red rice bran
      essential oils yield was 0.031%, and GC-MS analysis revealed that its major
      constituents were (E)-beta-ocimene (3.12%), nonanal (11.32%), (2E, 4E)-decadienal
      (2.54%), myristic acid (41.32%), geranyactone (2.41%) and methyl oleate (2.46%).
      The black rice bran essential oils yield was 0.053%, and GC-MS analysis revealed
      that its major constituents were nonanal (8.31%), acrylic acid (3.21%), 2-hydroxy
      6-methylbenzaldehyde (2.81%), pelargonic acid (4.21%) and myrisitc acid (28.07%).
      The essential oils showed inhibitory activity against complement system with 50%
      inhibitory concentrations (IC(50)) values of 246 ppm (red rice bran) and 193 ppm
      (black rice bran). Also, myristic acid, nonanal, (E)-beta-ocimene and pelargonic
      acid were tested against complement system. Pelargonic acid was shown to moderate
      activity (50% inhibitory concentration = 132 MUM).

PMID- 20673188
TI  - Cloning of the heat shock protein 60 gene from the stem borer, Chilo
      suppressalis, and analysis of expression characteristics under heat stress.
AB  - Heat shock protein 60 is an important chaperonin. In this paper, hsp60 of the
      stem borer, Chilo suppressalis (Walker) (Lepidoptera: Pyralidae), was cloned by
      RT-PCR and rapid amplification of cDNA end (RACE) reactions. The full length cDNA
      of hsp6 degrees Consisted of 2142 bp, with an ORF of 1719 bp, encoding 572 amino
      acid residues, with a 5'UTR of 158 bp and a 3'UTR of 265 bp. Cluster analysis
      confirmed that the deduced amino acid sequence shared high identity with the
      reported sequences from other insects (77%-86%). To investigate whether hsp60 in
      C. suppressalis responds to thermal stress, the expression levels of hsp60 mRNA
      in larval haemocytes across temperature gradients from 31 to 39 degrees C were
      analysed by real-time quantitative PCR. There was no significant difference for
      hsp60 expression from 28 to 31 degrees C. he temperatures for maximal induction
      of hsp60 expression in haemocytes was close to 36 degrees C. Hsp60 expression was
      observed by using flow cytometry. These results revealed that thermal stress
      significantly induced hsp60 expression and Hsp60 synthesis in larval haemocytes,
      and the expression profiles of Hsp60 at the mRNA and protein levels were in high
      agreement with each other from 33 to 39 degrees C.

PMID- 20673189
TI  - Morphology of the male reproductive system of the social wasp, Polistes
      versicolor versicolor, with phylogenetic implications.
AB  - Variation in the morphology of the adult male reproductive system among different
      groups of Hymenoptera offer characteristics that help studies of behavior and the
      evolutionary history of this group. The objective of this study was to describe
      the adult male reproductive system of the wasp Polistes versicolor versicolor
      Olivier (Vespidae: Polistini). The reproductive systems were dissected, fixed and
      embedded for light microscopy. In P. v. versicolor, the reproductive system
      includes a pair of testes, each one with three fusiform follicles. From each
      follicle emerges an efferent duct that later join together, forming a deferent
      duct. The first half of the deferent duct is enlarged and differentiated into a
      region specialized for sperm storage, the seminal vesicle. At the post-vesicular
      region of each of the deferent ducts an accessory gland emerges. The seminal
      vesicle and the accessory gland are covered with a capsule forming a vesicle
      gland complex, also observed in some species of North American Polistes. Sperm
      are released from testes in bundles, which are disorganized inside seminal
      vesicles. In the testicular follicles, 95 spermatozoa were observed per cyst on
      average.

PMID- 20673190
TI  - Wood litter consumption by three species of Nasutitermes termites in an area of
      the Atlantic Coastal Forest in northeastern Brazil.
AB  - Termites constitute a considerable fraction of the animal biomass in tropical
      forest, but little quantitative data are available that indicates their
      importance in the processes of wood decomposition. This study evaluated the
      participation of Nasutitermes corniger (Motschulsky) (Isoptera: Termitidae), N.
      ephratae (Holmgren), and N. macrocephalus (Silvestri) in the consumption of the
      wood litter in a remnant area of Atlantic Coastal Forest in northeastern Brazil.
      The populations of this species were quantified in nests and in decomposing tree
      trunks, while the rate of wood consumption was determined in the laboratory using
      wood test-blocks of Clitoria fairchildiana Howard (Fabales: Fabaceae), Cecropia
      sp. (Urticales: Cecropiaceae), and Protium heptaphyllum (Aublet) Marchand
      (Sapindales: Burseraceae). The abundance of the three species of termites varied
      from 40.8 to 462.2 individuals/m(2). The average dry wood consumption for the
      three species was 9.4 mg/g of termites (fresh weight)/day, with N. macrocephalus
      demonstrating the greatest consumption (12.1 mg/g of termite (fresh weight)/day).
      Wood consumption by the three species of Nasutitermes was estimated to be 66.9 kg
      of dry wood /ha/year, corresponding to approximately 2.9% of the annual
      production of wood-litter in the study area. This consumption, together with that
      of the other 18 exclusively wood-feeders termite species known to occur in the
      area, indicates the important participation of termites in removing wood-litter
      within the Atlantic Coastal Forest domain.

PMID- 20673191
TI  - A new method for distinguishing colony social forms of the fire ant, Solenopsis
      invicta.
AB  - Two distinct forms of colony social organization occur in the fire ant Solenopsis
      invicta Buren (Hymenoptera: Formicidae): colonies of the monogyne social form are
      headed by a single egg-laying queen, whereas those of the polygyne social form
      contain multiple egg-laying queens. This major difference in social organization
      is associated with genetic variation at a single gene (Gp-9) whereby all polygyne
      queens possess at least one b-like allele, while monogyne queens lack such b-like
      alleles and instead harbor B-like alleles only. Further, a recent study of native
      populations revealed that all b-like alleles in polygyne queens consistently
      contain three diagnostic amino acid residues: possession of only one or two of
      these critical residues is not sufficient for polygyny. TaqMan allelic
      discrimination assays were developed to survey the variable nucleotide sites
      associated with these three critical amino acid residues. The assays were
      validated by surveying nests of known social form from the species' introduced in
      the USA and from native South American ranges, as well as by comparing the
      results to Gp-9 sequence data from a subset of samples. The results demonstrate
      these new molecular assays consistently and accurately identify the variable
      nucleotides at all three sites characteristic of the B-like and b-like Gp-9
      allele classes, allowing for accurate determination of colony social form.

PMID- 20673192
TI  - Larval rearing temperature influences amount and composition of the marking
      pheromone of the male beewolf, Philanthus triangulum.
AB  - Pheromones play an important role for courtship and mating in many insect
      species, and they are shaped by a complex interaction of genetic and
      environmental factors. Developmental temperature is known to have a strong
      influence on adult life history, morphology, and physiology, but little is known
      about its effect on pheromone characteristics. In the present study, the
      influence of temperature during larval development on the amount and composition
      of the complex marking pheromone from the cephalic glands of the adult male
      beewolf, Philanthus triangulum F. (Hymenoptera: Crabronidae), was investigated.
      Additionally, the effects of temperature on several life-history traits were
      examined. European beewolf larvae were reared at three constant temperatures (20,
      25, and 30 degrees C). Males reared at 20 degrees C showed longer development
      times and higher mortality, suggesting that low temperatures constitute stressful
      conditions for developing larvae. After eclosion, the amount and composition of
      the scent marking secretion of the adult males was analyzed by coupled gas
      chromatography-mass spectrometry. Males that had been reared at 20 degrees C had
      significantly less secretion than individuals reared under warmer conditions (25
      degrees C and 30 degrees C). Furthermore, larval rearing temperature had a
      significant effect on the composition of the adult males' pheromone gland
      content, with warmer rearing conditions leading to higher relative amounts of
      compounds with high molecular weight. The results show that the temperature
      during larval development significantly affected the amount and composition of
      the content of the male pheromone glands, probably due to physiological
      constraints and competing processes for limited energetic resources. Thus, the
      pheromone gland content may contain information on developmental conditions of
      males, which may have consequences for female mate choice decisions and male
      reproductive success.

PMID- 20673193
TI  - Overwintering hosts for the exotic leafroller parasitoid, Colpoclypeus florus:
      implications for habitat manipulation to augment biological control of
      leafrollers in pome fruits.
AB  - Thirty sites of managed and native habitats were surveyed for leafrollers
      (Lepidoptera: Tortricidae) in the apple producing region of central Washington
      State and northern Oregon from September through November 1997-2000 to discover
      species that supported overwintering by the parasitoid Colpoclypeus florus
      (Walker) (Hymenoptera: Eulophidae). C. florus, a species introduced from Europe,
      requires medium to large host larvae late in autumn on which to overwinter, and
      few leafroller species display this biology. Over the four years, five potential
      C. florus hosts were collected, including: Ancylis comptana (Froelich), Xenotemna
      pallorana (Robinson), and Syndemis sp. (Tortricidae), Filatima sp. (Gelechiidae),
      and Caloptilia burgessiellia (Zeller) (Gracillariidae). Of these, A. comptana,
      Syndemis sp., and Filatima sp. have been confirmed as overwintering hosts for C.
      florus. During the four years, the Syndemis sp. was rare and observed at only one
      location feeding on redosier dogwood, Cornus sericea L. (Cornales: Cornaceae)
      although, at this location, many of the larvae collected were parasitized by C.
      florus. Filatima sp. was common in the Yakima valley feeding on balsam poplar,
      Populus balsamifera L. ssp. trichocarpa (Torr. & Gray ex Hook) Brayshaw
      (Malpighiales: Salicaceae) but was rarely parasitized. A. comptana, however, was
      collected at many locations in central Washington and was frequently found as an
      overwintering host for C. florus. A. comptana was found feeding on two Rosaceae:
      Wood's rose, Rosa woodsii Lindl., and strawberry, Fragaria ananassa Duchesne
      (Rosales: Rosaceae). Based on the number of host larvae collected, A. comptana
      appears to be the primary overwintering host for C. florus in Washington.
      Introduction of A. comptana populations to near-orchard habitats may facilitate
      biological control of leafrollers that are orchard pests.

PMID- 20673194
TI  - The complete mitochondrial genome sequence of the planthopper, Sivaloka damnosus.
AB  - The complete mitochondrial genome (mitogenome) sequence was determined from the
      plant hopper, Sivaloka damnosus Chow and Lu (Hemiptera: Issidae), a
      representative of the insect family Issidae. The genome is a circular molecule of
      15,287 bp with a total A+T content of 76.5%. The gene content, order, and
      structure are identical to that in Drosophila melanogaster, which is considered
      ancestral for insects. All 13 protein-coding genes of the S. damnosus mitogenome
      have a putative inframe ATR methionine or ATT isoleucine codons as start signals.
      The usual termination codons (TAA and TAG) were found in 11 protein-coding genes.
      However, atp6, and nad4 have incomplete termination codons. All tRNAs show stable
      canonical clover-leaf structures similar to other insect mitochondrial tRNAs,
      except for tRNA(Ser(AGN)), which has a reduced DHU arm. The A+T-rich region or
      putative control region includes two extensive repeat regions. The first repeat
      region is composed of two sets of complicated repeat units, and these repetitive
      sequences are arranged alternately; the second contains ten 20 bp tandemly
      repetitive sequences. In the phylogenetic analyses based on protein-coding genes,
      Cicadomorpha is a sister to Fulgoromorpha+Sternorrhyncha, and Heteroptera is a
      sister to all other Hemiptera.

PMID- 20673195
TI  - Impact of forest seral stage on use of ant communities for rapid assessment of
      terrestrial ecosystem health.
AB  - Bioassessment evaluates ecosystem health by using the responses of a community of
      organisms that integrate all aspects of the ecosystem. A variety of bioassessment
      methods have been applied to aquatic ecosystems; however, terrestrial methods are
      less advanced. The objective of this study was to examine baseline differences in
      ant communities at different seral stages from clear cut to mature pine
      plantation as a precursor to developing a broader terrestrial bioassessment
      protocol. Comparative sampling was conducted at nine sites having four seral
      stages: clearcut, 5 year recovery, 15 year recovery, and mature stands. Soil and
      vegetation data were also collected at each site. Ants were identified to genus.
      Analysis of the ant data indicated that ants respond strongly to habitat changes
      that accompany ecological succession in managed pine forests, and both individual
      genera and ant community structure can be used as indicators of successional
      change. Ants exhibited relatively high diversity in both early and mature seral
      stages. High ant diversity in mature seral stages was likely related to
      conditions on the forest floor favoring litter dwelling and cold climate
      specialists. While ants may be very useful in identifying environmental stress in
      managed pine forests, adjustments must be made for seral stage when comparing
      impacted and unimpacted forests.

PMID- 20673196
TI  - Purification and characterization of a new D-galactose-specific lectin from the
      housefly, Musca domestica, and its antiproliferative effect on human K562 and MCF
      7 tumor cells.
AB  - In the present work, a D-galactose-specific lectin with novel N-terminal sequence
      was purified from Musca domestica L. (Diptera: Muscidae) pupae. The purification
      was performed using affinity chromatography, ultra-filtration, and HPLC. The
      haemagglutinating activity of M. domestica lectin was specifically inhibited by D
      galactose. The haemagglutinating activity of this lectin was stable at
      temperatures up to 65 degrees C and in pH ranging from 4 to 8. Salts including
      FeCl(3) and MnCl(2) inhibited the haemagglutinating process, whereas NaCl, KCl,
      CaCl(2), MgCl(2), ZnCl(2), and AlCl(3) did not. By SDS-PAGE, purified M.
      domestica pupae lectin yielded a single band with a molecular weight of 40 kDa,
      with or without reduction of beta-mercaptoethanol, and it could be stained with
      Alcian Blue 8 GX. The morphology of purified lectin was observed by atomic force
      microscopy, which indicated that M. domestica lectin was an 8.27 nm high,
      globular shaped glycoprotein with a 1.41 nm high polysaccharide chain. In
      addition, antiproliferative activity of this lectin against tumor cells K562 and
      MCF-7 was determined with a colorimetric assay using 3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyl tetrazolium bromide, which showed that the antiproliferative process
      was time- and dose-dependent with an IC(50) of 5.7 and 6.7 at 24 h, 5.5 and 6.4
      at 36 h, 5.2 and 6.5 microM at 48 h, respectively.

PMID- 20673197
TI  - Effect of host change on demographic fitness of the parasitoid, Trichogramma
      brassicae.
AB  - Trichogramma brassicae (Bezdenko) is the most important species of Trichogramma
      parasitoids in Iran. The cotton bollworm, Helicoverpa armigera (Hubner) is a
      polyphagous insect pest that attacks many crops including cotton, maize, soybean,
      tomato, etc. The bollworm egg is a suitable target for many Trichogramma species.
      Factitious hosts such as eggs of the flour moth, Anagasta kuehniella (Zeller) and
      cereal moth, Sitotroga cerealella (Hubner) are used for mass rearing purposes.
      But a problem that arises sometimes in laboratory cultures is the development of
      a tendency toward laboratory hosts following a few generations rearing with them.
      This may tend to a low efficiency on target pest in field conditions. In this
      study the possibility of declining efficiency of the parasitoid on target pest by
      developing such a preference to alternative hosts in previous generations were
      investigated when the flour moth or cereal moth uses as laboratory host. Two
      generations of T. brassicae were reared on each of the mentioned hosts and then
      transferred to H. armigera eggs for two further generations. The intrinsic rate
      of natural increase as well as other life table parameters were used for
      monitoring fitness of the parasitoid at successive generations. Even generations
      were included to determine if previously rearing host affected parasitoid
      performance. Results revealed that host shift from cereal moth to bollworm caused
      a sudden fall in population growth parameters (both intrinsic rate of natural
      increase and net replacement rate). Further rearing on bollworm eggs led to a
      relapse in both parameters. No similar effect was observed in cultures initiated
      with the flour moth. As a whole, cereal moth was a more suitable host than flour
      moth.

PMID- 20673198
TI  - Medical and cost burden of atherosclerosis among patients treated in routine
      clinical practice.
AB  - OBJECTIVE: This investigation estimated medical costs attributable to treatment
      of patients diagnosed with atherosclerosis in routine US clinical practice.
      METHODS: Using Medstat MarketScan claims data, direct costs of care and rates of
      cardiovascular (CV) events (i.e., myocardial infarction, stroke,
      revascularization) were examined for patients>=18 years of age with and without a
      diagnostic code for atherosclerosis from 1/1/2002 through 12/31/2004. Patients
      with an atherosclerosis ICD-9 code who had no history of CV events in the
      preceding 12 months (n=75,469) were evaluated. A comparison cohort (n=238,702)
      was matched on age, gender, geographic region, enrollment time period, and
      Charlson comorbidity index to estimate incremental costs attributable to
      atherosclerosis. Differences between patient groups were tested for CV event
      rates per 1,000 patients and monthly costs for 6 and 12 months before and after
      diagnosis. RESULTS: Patients had a mean age of 58 years, 52% men, and a
      comorbidity index of 0.49. Patients diagnosed with atherosclerosis had
      significantly higher (p<0.001) rates of CV events (240/1000) after diagnosis,
      compared with patients without atherosclerosis (32/1000). Mean direct cost of
      care for patients diagnosed with atherosclerosis was $579/month for 12 months
      before and $1,074/month for 12 months after diagnosis, an 85% increase. Change in
      mean annual costs pre/post-index date was $5,232 ($436/month) higher among
      patients with than those without atherosclerosis (p<0.001). LIMITATIONS: The
      study population was restricted to patients with diagnosed clinical
      atherosclerosis based on specific ICD-9 codes. Matching of the patient cohorts
      was based on observed characteristics and other unobserved differences may exist.
      CONCLUSIONS: Patients with diagnosed atherosclerosis incur significant clinical
      and economic burden, indicating a need for earlier diagnosis and treatment of
      atherosclerosis to help in reducing this burden.

PMID- 20673200
TI  - Comparison of the effects of dorzolamide/timolol and latanoprost/timolol fixed
      combinations upon intraocular pressure and progression of visual field damage in
      primary open-angle glaucoma.
AB  - OBJECTIVE: To report the long-term effect of the dorzolamide/timolol (DTFC) and
      latanoprost/timolol (LTFC) fixed combinations on intraocular pressure (IOP) and
      visual field defects over time in naive primary open-angle glaucoma (POAG)
      patients. STUDY DESIGN AND METHODS: Prospective, 4-year, open-label,
      interventional study. SETTING: high-volume outpatient clinic. PATIENTS: 178
      patients were assigned to receive medical treatment with either DTFC or LTFC.
      INTERVENTION: over 4 years, tri-monthly IOP and yearly visual field assessment
      (Octopus 101, Program G2). outcomes: effect of treatment on IOP, visual field
      indices mean defect (MD), and visual field indices variance loss (VL) over time.
      RESULTS: DTFC and LTFC significantly (p < or = 0.001) reduced mean IOP over time
      (from 22.6 +/- 3.0 to 13.8 +/- 1.9 mmHg and from 22.3 +/- 4.0 to 14.7 +/- 1.9
      mmHg, respectively). In all, 56 patients (70.9%) and 14 (17.9%) showed a
      significant MD improvement in the DTFC- and LTFC-treated groups, respectively, p
      = 0.0001. DTFC progressively and significantly decreased mean VL (from 30.21 +/-
      23.88 to 8.11 +/- 8.50 dB). Mean sensitivity slopes during follow-up were 1.14
      dB/year and -0.34 dB/year for DTFC and LTFC treatment groups, respectively; p =
      0.028. CONCLUSION: Both treatments significantly reduced IOP as compared with
      baseline. Additionally, treatment with dorzolamide/timolol fixed combination seem
      to be effective in preventing glaucomatous visual field progression. This study
      has some limitations that should be noted, among them its open-label design.

PMID- 20673201
TI  - Chart review of patients on valsartan-based single-pill combinations vs. ARB
      based free combinations for BP goal achievement.
AB  - OBJECTIVE: To compare blood pressure (BP) goal achievement associated with the
      use of valsartan-based single pill combinations (SPCs) vs. angiotensin II
      receptor blocker (ARB)-based free combinations (FCs) among adult hypertension
      patients. RESEARCH DESIGN AND METHODS: Data were collected from physician
      administered chart review of adult hypertension patients in the South Central
      region. All patients had uncontrolled BP before initiating one of the index
      therapies (SPCs: valsartan/amlodipine or valsartan/hydrochlorothiazide [HCTZ],
      FCs: ARB + calcium channel blocker [CCB] or ARB + HCTZ) between 07/2008 and
      06/2009. Up to three BP measures were collected starting from 45 days after the
      therapy initiation. BP goal was <130/80 mmHg for patients with diabetes, chronic
      renal disease or coronary heart disease; or <140/90 mmHg for patients without
      these comorbidities. The Kaplan-Meier method with log-rank test was used to
      compare rates of BP goal achievement associated with valsartan-based SPCs vs. ARB
      based FCs over time. Cox proportional hazard models were used to estimate the
      likelihood of BP goal achievement associated with SPCs vs. FCs, controlling for
      demographics, baseline BP, hypertension history, comorbidities, prior and
      concurrent use of anti-hypertensive medications, and physician specialty.
      RESULTS: The study included 812 patients: 414 on valsartan-based SPCs (209 on
      valsartan/amlodipine and 205 on valsartan/HCTZ) and 398 on ARB-based FCs (200 on
      ARB + CCB and 198 on ARB + HCTZ). The ARBs in the FC group included valsartan,
      losartan, olmesartan, telmisartan, irbesartan and candesartan. In the ARB FC
      group, the most commonly used ARB and CCB were valsartan (29.1%) and amlodipine
      (81.5%), respectively. During the observation period (81 days for valsartan SPC
      patients and 90 days for ARB FC patients), 65.9% of valsartan SPC patients and
      55.8% of the ARB FC patients achieved BP goal. Over time, the rates of BP goal
      achievement were consistently higher among valsartan SPC vs. ARB FC patients (p =
      0.01): 31.1% vs. 28.9% and 69.1% vs. 59.2% at month 3 and 6 after therapy
      initiation, respectively. Cox regression confirmed that valsartan SPC patients
      were more likely to achieve BP goal (HR = 1.22; p = 0.05). A similar trend was
      observed in the subgroup analyses comparing SPC of valsartan/amlodipine vs. FCs
      of ARB + CCB and SPC of valsartan/HCTZ vs. FCs of ARB + HCTZ. LIMITATIONS: Non
      randomization of treatments, limited generalizability, and no records of BP
      measures within 45 days. CONCLUSIONS: Patients using valsartan-based SPCs were
      significantly more likely to achieve BP goal than those treated with ARB-based
      FCs in the real-world clinical practice in the South Central region. The
      significance was achieved at two-sided alpha = 0.05.

PMID- 20673203
TI  - Lipid signaling in the atherogenesis context.
AB  - Normally macrophages localized in the arterial vessel wall perform the "reverse
      transfer" of cholesterol, which includes endocytosis of low density lipoproteins
      (LDL), cholesterol transfer to newly formed high density lipoprotein particles,
      and their following elimination by the liver. The homeostatic function of
      macrophages for cholesterol involves a system of lipid sensors. Oxysterol sensors
      LXRs, oxysterol and cholesterol sensors INSIG and SCAP acting through controlled
      transcription factors SREBP, as well as sensors for oxidized fatty acids and
      their derivatives, PPAR, are the best studied. Activation of LXR and PPAR is also
      accompanied by inhibition of macrophage functions related to inflammation.
      Accumulation of oxidized and otherwise modified LDL in the subendothelial space
      induced by endothelium injury, infection, or other pathogenic factors instead of
      stimulation of the homeostatic functions of macrophages leads to their weakening
      with a concurrent increase in the inflammatory potential of these cells. These
      shifts seem to drive the transformation of macrophages into foam cells, which
      form the core of sclerotic plaques. The intervention of another lipid sensor,
      TLR4, can trigger such a radical change in the functional activity of
      macrophages. The interaction of modified LDL with this signaling receptor results
      in inhibition of the homeostatic oxysterol signaling, induction of additional LDL
      transporters, and activation of the phagocytic function of macrophages. The re
      establishment of cholesterol homeostasis under these circumstances can be
      achieved by administration of LXR and PPARgamma agonists. Therefore, it is urgent
      to design ligands with reduced side effects.

PMID- 20673204
TI  - "Smart" liposomal nanocontainers in biology and medicine.
AB  - The perspectives of using liposomes for delivery of drugs to desired parts of the
      human body have been intensively investigated for more than 30 years. During this
      time many inventions have been suggested and different kinds of liposomal devices
      developed, and a number of them have reached the stages of preclinical or
      clinical trials. The latest techniques can be used to develop biocompatible nano
      sized liposomal containers having some abilities of artificial intellect, such as
      the presence of sensory and responsive units. However, only a few have been
      clinically approved. Further improvements in this area depend on our knowledge of
      the interactions of drugs with the lipid bilayer of liposomes. Further studies on
      liposomal transport through the human body, their targeting of cells requiring
      therapeutic treatment, and finally, the development of techniques for controlled
      drug delivery to desired acceptors on cell surfaces or in cytoplasm are still
      required.

PMID- 20673202
TI  - Significance of brain tissue oxygenation and the arachidonic acid cascade in
      stroke.
AB  - The significance of the hypoxia component of stroke injury is highlighted by
      hypermetabolic brain tissue enriched with arachidonic acid (AA), a 22:6n-3
      polyunsaturated fatty acid. In an ischemic stroke environment in which cerebral
      blood flow is arrested, oxygen-starved brain tissue initiates the rapid cleavage
      of AA from the membrane phospholipid bilayer. Once free, AA undergoes both enzyme
      independent and enzyme-mediated oxidative metabolism, resulting in the formation
      of number of biologically active metabolites which themselves contribute to
      pathological stroke outcomes. This review is intended to examine two divergent
      roles of molecular dioxygen in brain tissue as (1) a substrate for life
      sustaining homeostatic metabolism of glucose and (2) a substrate for pathogenic
      metabolism of AA under conditions of stroke. Recent developments in research
      concerning supplemental oxygen therapy as an intervention to correct the hypoxic
      component of stroke injury are discussed.

PMID- 20673205
TI  - Inorganic polyphosphates in mitochondria.
AB  - Current data concerning the crucial role of inorganic polyphosphates (polyP) in
      mitochondrial functions and dysfunctions in yeast and animal cells are reviewed.
      Biopolymers with short chain length (approximately 15 phosphate residues) were
      found in the mitochondria of Saccharomyces cerevisiae. They comprised 7-10% of
      the total polyP content of the cell. The polyP are located in the membranes and
      intermembrane space of mitochondria. The mitochondrial membranes possess
      polyP/Ca2+/polyhydroxybutyrate complexes. PolyP accumulation is typical of
      promitochondria but not of functionally active mitochondria. Yeast mitochondria
      possess two exopolyphosphatases splitting P(i) from the end of the polyP chain.
      One of them, encoded by the PPX1 gene, is located in the matrix; the other one,
      encoded by the PPN1 gene, is membrane-bound. Formation of well-developed
      mitochondria in the cells of S. cerevisiae after glucose depletion is accompanied
      by decrease in the polyP level and the chain length. In PPN1 mutants, the polyP
      chain length increased under glucose consumption, and the formation of well
      developed mitochondria was blocked. These mutants were defective in respiration
      functions and consumption of oxidizable carbon sources such as lactate and
      ethanol. Since polyP is a compound with high-energy bonds, its metabolism vitally
      depends on the cell bioenergetics. The maximal level of short-chain acid-soluble
      polyP was observed in S. cerevisiae under consumption of glucose, while the long
      chain polyP prevailed under ethanol consumption. In insects, polyP in the
      mitochondria change drastically during ontogenetic development, indicating
      involvement of the polymers in the regulation of mitochondrial metabolism during
      ontogenesis. In human cell lines, specific reduction of mitochondrial polyP under
      expression of yeast exopolyphosphatase PPX1 significantly modulates mitochondrial
      bioenergetics and transport.

PMID- 20673206
TI  - Primary electron transfer in reaction centers of YM210L and YM210L/HL168L mutants
      of Rhodobacter sphaeroides.
AB  - The role of tyrosine M210 in charge separation and stabilization of separated
      charges was studied by analyzing of the femtosecond oscillations in the kinetics
      of decay of stimulated emission from P* and of a population of the primary charge
      separated state P(+)B(A)(-) in YM210L and YM210L/HL168L mutant reaction centers
      (RCs) of Rhodobacter sphaeroides in comparison with those in native Rba.
      sphaeroides RCs. In the mutant RCs, TyrM210 was replaced by Leu. The HL168L
      mutation placed the redox potential of the P(+)/P pair 123 mV below that of
      native RCs, thus creating a theoretical possibility of P(+)B(A)(-) stabilization.
      Kinetics of P* decay at 940 nm of both mutants show a significant slowing of the
      primary charge separation reaction in comparison with native RCs. Distinct damped
      oscillations in these kinetics with main frequency bands in the range of 90-150
      cm(-1) reflect mostly nuclear motions inside the dimer P. Formation of a very
      small absorption band of B(A)(-) at 1020 nm is registered in RCs of both mutants.
      The formation of the B(A)(-) band is accompanied by damped oscillations with main
      frequencies from ~10 to ~150 cm(-1). Only a partial stabilization of the
      P(+)B(A)(-) state is seen in the YM210L/HL168L mutant in the form of a small non
      oscillating background of the 1020-nm kinetics. A similar charge stabilization is
      absent in the YM210L mutant. A model of oscillatory reorientation of the OH-group
      of TyrM210 in the electric fields of P(+) and B(A)(-) is proposed to explain
      rapid stabilization of the P(+)B(A)(-) state in native RCs. Small oscillatory
      components at ~330-380 cm(-1) in the 1020-nm kinetics of native RCs are assumed
      to reflect this reorientation. We conclude that the absence of TyrM210 probably
      cannot be compensated by lowering of the P(+)B(A)(-) free energy that is expected
      for the double YM210L/HL168L mutant. An oscillatory motion of the HOH55 water
      molecule under the influence of P(+) and B(A)(-) is assumed to be another
      potential contributor to the mechanism of P(+)B(A)(-) stabilization.

PMID- 20673207
TI  - Mapping the ribosomal protein S7 regulatory binding site on mRNA of the E. coli
      streptomycin operon.
AB  - In this work it is shown by deletion analysis that an intercistronic region (ICR)
      approximately 80 nucleotides in length is necessary for interaction with
      recombinant E. coli S7 protein (r6hEcoS7). A model is proposed for the
      interaction of S7 with two ICR sites-region of hairpin bifurcations and Shine
      Dalgarno sequence of cistron S7. A de novo RNA binding site for heterologous S7
      protein of Thermus thermophilus (r6hTthS7) was constructed by selection of a
      combinatorial RNA library based on E. coli ICR: it has only a single supposed
      protein recognition site in the region of bifurcation. The SERW technique was
      used for selection of two intercistronic RNA libraries in which five nucleotides
      of a double-stranded region, adjacent to the bifurcation, had the randomized
      sequence. One library contained an authentic AG (-82/-20) pair, while in the
      other this pair was replaced by AU. A serwamer capable of specific binding to
      r6hTthS7 was selected; it appeared to be the RNA68 mutant with eight nucleotide
      mutations. The serwamer binds to r6hTthS7 with the same affinity as homologous
      authentic ICR of str mRNA binds to r6hEcoS7; apparent dissociation constants are
      89 +/- 43 and 50 +/- 24 nM, respectively.

PMID- 20673208
TI  - State of oncomarker protein B23/nucleophosmin in HeLa cells.
AB  - Western blot after SDS-PAGE for protein separation showed two immunoreactive
      bands corresponding to monomers (38-40 kDa) and oligomers (210-230 kDa) of
      nucleophosmin in HeLa cell lysates. Decreasing the buffer ionic strength during
      the incubation of cells and nuclei destabilized these oligomers. We also showed
      the existence of two B23/nucleophosmin pools in nuclei of HeLa cells with
      different sensitivity to hypotonic buffer treatment: one extractable from the
      nucleus and the other non-extractable and tightly bound to the nucleus. A
      detailed structural analysis of the extractable B23 pool was carried out: two
      closely related nucleophosmin isoforms (B23.1 and B23.2) were identified as a
      result of analysis of C-terminal amino acid sequences using carboxypeptidase
      hydrolysis; the N-termini of both isoforms are blocked by an acetyl group. As a
      result of sequencing of the deacetylated proteins, it has been established that
      the N-terminal amino acid sequence of nucleophosmin in these preparations is
      truncated by nine amino acid residues and the acetylated residue is Ser. The
      truncated monomer of nucleophosmin (represented only by the extractable part of
      the protein) on addition of magnesium ions to low ionic strength buffer or
      increase in buffer ionic strength was shown to form oligomers with molecular
      weights (210-230 kDa) similar to those revealed in the total cell lysate. It
      should be noted that the set of oligomers in this case differs from the one in
      total cell lysate. Our strategy of characterization of B23 forms for HeLa cells
      can be applied for other tumor cells.

PMID- 20673209
TI  - Recombinant maize 9-lipoxygenase: expression, purification, and properties.
AB  - Expression of maize 9-lipoxygenase was performed and optimized in Escherichia
      coli Rosetta(DE3)pLysS. The purity of recombinant protein obtained during Q
      Sepharose and Octyl-Sepharose chromatographies in an LP system at 4 degrees C was
      >95%. Maximum activity of the lipoxygenase reaction was observed at pH 7.5.
      Enzyme stability was studied at pH 4.5 to 9.5 and in the presence of different
      compounds: phenylmethanesulfonyl fluoride, beta-mercaptoethanol, ammonium
      sulfate, and glycerol. HPLC and GC-MS analysis showed that enzyme produced 99% 9S
      hydroperoxide from linoleic acid. 13-Hydroperoxide (less than 1%) consisted of S-
      and R-enantiomers in ratio 2 : 3.

PMID- 20673210
TI  - Isolation, purification, and study of properties of recombinant hepsin from
      Escherichia coli.
AB  - A recombinant hepsin-producing strain of Escherichia coli was obtained and the
      conditions for hepsin expression in a bacterial system were optimized. To study
      the physicochemical properties of the enzyme, a procedure for purification of
      active recombinant hepsin using metal-chelate affinity chromatography and ion
      exchange chromatography was developed. The interaction of recombinant hepsin with
      various peptide substrates is characterized. The dose-dependent inhibition of the
      recombinant hepsin enzyme activity by anthralin in vitro and an increase in the
      hepsin enzymatic activity in the presence of resveratrol were revealed.

PMID- 20673211
TI  - Isolation and properties of human transketolase.
AB  - Recombinant human (His)(6)-transketolase (hTK) was obtained in preparative
      amounts by heterologous expression of the gene encoding human transketolase in
      Escherichia coli cells. The enzyme, isolated in the form of a holoenzyme, was
      homogeneous by SDS-PAGE; a method for obtaining the apoenzyme was also developed.
      The amount of active transketolase in the isolated protein preparation was
      correlated with the content of thiamine diphosphate (ThDP) determined in the same
      preparation. Induced optical activity, facilitating studies of ThDP binding by
      the apoenzyme and measurement of the transketolase reaction at each stage, was
      detected by circular dichroism spectroscopy. A single-substrate reaction was
      characterized, catalyzed by hTK in the presence of the donor substrate and in the
      absence of the acceptor substrate. The values of the Michaelis constant were
      determined for ThDP and a pair of physiological substrates of the enzyme
      (xylulose 5-phosphate and ribose 5-phosphate).

PMID- 20673212
TI  - Expression of G-protein coupled receptors in Escherichia coli for structural
      studies.
AB  - To elaborate a high-performance system for expression of genes of G-protein
      coupled receptors (GPCR), methods of direct and hybrid expression of 17 GPCR
      genes in Escherichia coli and selection of strains and bacteria cultivation
      conditions were investigated. It was established that expression of most of the
      target GPCR fused with the N-terminal fragment of OmpF or Mistic using media for
      autoinduction provides high output (up to 50 mg/liter).

PMID- 20673213
TI  - Characterization of recombinant fructose-1,6-bisphosphate aldolase from
      Methylococcus capsulatus Bath.
AB  - The gene fba from the thermotolerant obligate methanotroph Methylococcus
      capsulatus Bath was cloned and expressed in Escherichia coli BL21(DE3). The
      fructose-1,6-bisphosphate aldolase (FBA) carrying six His on the C-end was
      purified by affinity metal chelating chromatography. The Mc. capsulatus FBA is a
      hexameric enzyme (240 kDa) that is activated by Co2+ and inhibited by EDTA. The
      enzyme displays low K(m) to fructose-1,6-bisphosphate (FBP) and higher K(m) to
      the substrates of aldol condensation, dihydroxyacetone phosphate and
      glyceraldehyde-3-phosphate. The FBA also catalyzes sedoheptulose-1,7-bisphosphate
      cleavage. The presence of Co2+ in the reaction mixture changes the kinetics of
      FBP hydrolysis and is accompanied by inhibition of the reaction by 2 mM FBP.
      Phylogenetically, the Mc. capsulatus enzyme belongs to the type B of class II
      FBAs showing high identity of translated amino acid sequence with FBAs from
      autotrophic bacteria. The role of the FBA in metabolism of Mc. capsulatus Bath,
      which realizes simultaneously three C(1) assimilating pathways (the ribulose
      monophosphate, the ribulose bisphosphate, and the serine cycles), is discussed.

PMID- 20673214
TI  - Conformational changes near the cytochrome P450 active site upon binding of two
      different ligands.
AB  - It is shown that a stable nitroxyl radical, 4-cyano-2,2,6,6-tetramethylpiperidine
      1-oxyl, forms a complex with cytochrome P4502B4 by analogy with the second type
      substrates by joining directly to pentacoordinate heme iron. The bound radical is
      inaccessible to water-soluble paramagnetic ions, which confirms its localization
      in a hydrophobic pocket near the heme. Benzphetamine and N,N-dimethylaniline, the
      first-type nonpolar substrates, induce conformational changes of the spin-labeled
      hemoprotein which are evidently accompanied by an increase in the volume of the
      pocket resulting in emergence of contact with aqueous phase, and the heme-bound
      spin label becomes accessible to water-soluble paramagnetics. In this case
      potassium ferricyanide broadens the spin-labeled cytochrome signal and, as a
      result, lowers the amplitudes of the spectral components. Similar changes were
      registered at non-micellar concentrations of nonionic detergent Emulgen 913,
      whose activating effect on hydroxylation reactions is associated, as we showed
      previously, with its presence in the CYP2B4 active site simultaneously with
      substrates.

PMID- 20673215
TI  - Effect of human cell malignancy on activity of DNA polymerase iota.
AB  - An increased level of mutagenesis, partially caused by imbalanced activities of
      error prone DNA polymerases, is a key symptom of cell malignancy. To clarify the
      possible role of incorrect DNA polymerase iota (Pol iota) function in increased
      frequency of mutations in mammalian cells, the activity of this enzyme in
      extracts of cells of different mouse organs and human eye (melanoma) and eyelid
      (basal-cell skin carcinoma) tumor cells was studied. Both Mg2+, considered as the
      main activator of the enzyme reaction of in vivo DNA replication, and Mn2+, that
      activates homogeneous Pol iota preparations in experiments in vitro more
      efficiently compared to all other bivalent cations, were used as cofactors of the
      DNA polymerase reaction in these experiments. In the presence of Mg2+, the enzyme
      was active only in cell extracts of mouse testicles and brain, whereas in the
      presence of Mn2+ the activity of Pol iota was found in all studied normal mouse
      organs. It was found that in cell extracts of both types of malignant tumors
      (basal-cell carcinoma and melanoma) Pol iota activity was observed in the
      presence of either Mn2+ or Mg2+. Manganese ions activated Pol iota in both cases,
      though to a different extent. In the presence of Mn2+ the Pol iota activity in
      the basal-cell carcinoma exceeded 2.5-fold that in control cells (benign tumors
      from the same eyelid region). In extracts of melanoma cells in the presence of
      either cation, the level of the enzyme activity was approximately equal to that
      in extracts of cells of surrounding tumor-free tissues as well as in eyes removed
      after traumas. The distinctive feature of tissue malignancy (in basal-cell
      carcinoma and in melanoma) was the change in DNA synthesis revealed as Mn2+
      activated continuation of DNA synthesis after incorrect incorporation of dG
      opposite dT in the template by Pol iota. Among cell extracts of different normal
      mouse organs, only those of testicles exhibited a similar feature. This
      similarity can be explained by cell division blocking that occurs in all normal
      cells except in testicles and in malignant cells.

PMID- 20673216
TI  - Nature of cation-pi interactions and their role in structural stability of
      immunoglobulin proteins.
AB  - Cation-pi interactions are known to be important contributors to protein
      stability and ligand-protein interactions. In this study, we have analyzed the
      influence of cation-pi interactions in single chain immunoglobulin proteins. We
      observed 87 cation-pi interactions in a data set of 33 proteins. These
      interactions are mainly formed by long-range contacts, and there is preference of
      Arg over Lys in these interactions. Arg-Tyr interactions are predominant among
      the various pairs analyzed. Despite the scarcity of interactions involving Trp,
      the average energy for Trp-cation interactions is quite high. This information
      suggests that the cation-pi interactions involving Trp might be of high relevance
      to the proteins. Secondary structure analysis reveals that cation-pi interactions
      are formed preferably between residues in which at least one is in beta-strand.
      Proteins having beta-strand regions have the highest number of cation-pi
      interaction-forming residues.

PMID- 20673217
TI  - Effects of C-terminal truncation on autocatalytic processing of Bacillus
      licheniformis gamma-glutamyl transpeptidase.
AB  - The role of the C-terminal region of Bacillus licheniformis gamma-glutamyl
      transpeptidase (BlGGT) was investigated by deletion analysis. Seven C-terminally
      truncated BlGGTs lacking 581-585, 577-585, 576-585, 566-585, 558-585, 523-585,
      and 479-585 amino acids, respectively, were generated by site-directed
      mutagenesis. Deletion of the last nine amino acids had no appreciable effect on
      the autocatalytic processing of the enzyme, and the engineered protein was active
      towards the synthetic substrate L-gamma-glutamyl-p-nitroanilide. However, a
      further deletion to Val576 impaired the autocatalytic processing. In vitro
      maturation experiments showed that the truncated BlGGT precursors, pro-Delta(576
      585), pro-Delta(566-585), and pro-Delta(558-585), could partially precede a time
      dependent autocatalytic process to generate the L- and S-subunits, and these
      proteins showed a dramatic decrease in catalytic activity with respect to the
      wild-type enzyme. The parental enzyme (BlGGT-4aa) and BlGGT were unfolded
      biphasically by guanidine hydrochloride (GdnCl), but Delta(577-585), Delta(576
      585), Delta(566-585), Delta(558-585), Delta(523-585), and Delta(479-585) followed
      a monophasic unfolding process and showed a sequential reduction in the GdnCl
      concentration corresponding to half effect and DeltaG(0) for the unfolding. BlGGT
      4aa and BlGGT sedimented at ~4.85 S and had a heterodimeric structure of
      approximately 65.23 kDa in solution, and this structure was conserved in all of
      the truncated proteins. The frictional ratio (f/f(o)) of BlGGT-4aa, BlGGT,
      Delta(581-585), and Delta(577-585) was 1.58, 1.57, 1.46, and 1.39, respectively,
      whereas the remaining enzymes existed exclusively as precursor form with a ratio
      of less than 1.18. Taken together, these results provide direct evidence for the
      functional role of the C-terminal region in the autocatalytic processing of
      BlGGT.

PMID- 20673218
TI  - Characterization of a new RNase HII and its essential amino acid residues in the
      archaeon Sulfolobus tokodaii reveals a regulatory C-terminus.
AB  - The archaea possess RNase H proteins that share features of both prokaryotic and
      eukaryotic forms. Although the Sulfolobus RNase HI has been reported to have
      unique structural and biochemical properties, its RNase HII has not yet been
      investigated and its biochemical properties remain unknown. In the present study,
      we have characterized the ST0519 RNase HII from S. tokodaii as a new form. The
      enzyme utilized hybrid RNA/DNA as a substrate and had an optimal temperature
      between 37 to 50 degrees C. The activity of wild-type protein was stimulated by
      Mn2+, whereas this cation significantly inhibited the activity of C-terminal
      truncated mutant proteins. A series of mutation assays revealed a regulatory C
      terminal tail in the S. tokodaii RNase HII. One mutant, ST0519 (residues 1-195),
      retained only partial activity, while ST0519 (residues 1-196) completely lost its
      activity. Based on the presumed structure, the C-terminus might form a short
      alpha-helix in which two residues, I195 and L196, are essential for the cleavage
      activity. Our data suggest that the C-terminal alpha-helix is likely involved in
      the Mn2+-dependent substrate cleavage activity through stabilization of a
      flexible loop structure. Our findings offer important clues for further
      understanding the structure and function of both archaeal and eukaryotic RNase
      HII.

PMID- 20673219
TI  - Isoforms of human O-GlcNAcase show distinct catalytic efficiencies.
AB  - O-GlcNAcase (OGA) is a family 84 glycoside hydrolase catalyzing the hydrolytic
      cleavage of O-linked beta-N-acetylglucosamine (O-GlcNAc) from serine and
      threonine residues of proteins. Thus far, three forms of OGA have been identified
      in humans. Here we optimized the expression of these isoforms in E. coli and
      characterized their kinetic properties. Using Geno 3D, we predicted that N
      terminal amino acids 63-342 form the catalytic site for O-GlcNAc removal and
      characterized it. Large differences are observed in the K(m) value and catalytic
      efficiency (k(cat)/K(m)) for the three OGA variants, though all of them displayed
      O-GlcNAc hydrolase activity. The full-length OGA had the lowest K(m) value of
      0.26 mM and the highest catalytic efficiency of 3.51.10(3). These results reveal
      that the N-terminal region (a.a. 1-350) of OGA contains the catalytic site for
      glycoside hydrolase and the C-terminal region of the coding sequence has the
      ability to stabilize the native three-dimensional structure and further affect
      substrate affinity.

PMID- 20673220
TI  - An easy colorimetric assay for glycosyltransferases.
AB  - Glycosyltransferases are involved in biosynthesis of both protein-bound and non
      bound glycans that have multiple and important biological functions in all
      species. A variety of methods for assaying glycosyltransferase activity have been
      developed driven by the specific interests and type of information required by
      researchers. In this work, a novel colorimetric assay for the glycosyltransferase
      catalyzed reaction was established. Compared with measuring the newly formed
      product, which might not exhibit visible absorption, the unreacted acceptor could
      be readily detected by measuring the visible absorption of the hydrolysis
      product. In the assay, 4-nitrophenyl-beta-D-glycoside (glycosyl-beta-pNP) is used
      as the glycosyl acceptor, which can be hydrolyzed by a special exoglycosidase to
      release the p-nitrophenol before glycosylation reactions. Absorbance change of
      the p-nitrophenolate corresponds to unreacted glycosyl acceptor that accompanied
      the glycosyl transfer. The assay is demonstrated to be useful in the initial
      characterization of recombinant glycosyltransferases for their kinetic
      parameters, optimal metal cofactor, and pH value. It provides a simple,
      sensitive, and quantitative method for assessing glycosyltransferase activity and
      is thus expected to have broad applications including automated high-throughput
      screening.

PMID- 20673221
TI  - Efficient synthesis of stable phosphonate ylides and phosphonate esters: reaction
      between activated acetylenes and triphenylphosphite in the presence of
      sulfonamide and heterocyclic NH-acids.
AB  - An efficient synthesis of stable phosphonate ylides and phosphonate esters is
      described via a one-pot reaction between activated acetylenes and
      triphenylphosphite in the presence of sulfonamides and heterocyclic NH-acids.
      Single X-ray diffraction analysis and NMR studies were used in characterizing the
      ylides and phosphonate ester products. Dynamic NMR studies performed on a
      phosphonate ylide allowed the calculation of the free energy barrier for the
      inter-conversion between the geometrical isomers (E) and (Z).

PMID- 20673222
TI  - Modulation of apoptosis: new opportunities for drug discovery to treat autoimmune
      thyroiditis.
AB  - The balance between apoptosis and cell proliferation is the key determinant in
      the pathogenesis of many diseases including autoimmune thyroiditis. In recent
      years, many studies have strengthened the concept that pro- and anti-apoptotic
      molecules expressed in thyroid epithelial cells as well as in thyroid
      infiltrating lymphocytes play a pivotal role in the pathogenesis and/or
      progression of autoimmune thyroiditis. In this review, the role of apoptosis in
      the pathogenesis in the two well-defined murine models of autoimmune thyroiditis,
      experimental autoimmune thyroiditis (EAT) and iodine-induced autoimmune
      thyroiditis (IAT) is discussed. Recent important patents focusing on apoptosis as
      novel therapeutic targets are also discussed in this review. Further clinical
      trials are needed to evaluate the efficacy and safety of these agents.

PMID- 20673223
TI  - Regulatory T cells and skin tumors.
AB  - Regulatory T cells (Tregs) are essential for maintaining self-tolerance and also
      play a pivotal role in diminishing anti-tumor immunoresponse. The frequency and
      activity of CD4(+)CD25(+)FoxP3(+) Tregs in the circulation and tumor
      microenvironment is increased in patients with various cancers. Although, the
      exact role of Tregs in cutaneous tumors remains unclear, Tregs contribute to
      tumor progression of skin cancers, explaining, in part, why immunotherapy with
      dendritic cell-based vaccination for melanoma patients has not been satisfactory.
      Therefore, there has been considerable interest in determining their function in
      order to treat skin cancers such as malignant melanoma. However, clinical trials
      with specific antibodies designed to overcome Treg-associated immunosuppression
      resulted in limited clinical efficacy with some adverse effects. A better
      understanding of the role of Tregs in the tumor environment might contribute to
      the development of novel approaches for treating various cutaneous tumors. In
      this review, we focus on clinical and basic research on Tregs in relation to skin
      tumors and describe some important patents for the treatment of skin cancers.

PMID- 20673224
TI  - Physicochemical and biological characterization of anti-endotoxin peptides and
      their influence on lipid properties.
AB  - We have synthesized a series of short peptides (17 to 20 amino acids), originally
      derived from Limulus anti-lipopolysaccharide factor LALF, which were primarily
      designed to act as antimicrobial agents as well as neutralizers of bacterial
      endotoxin (lipopolysaccharide, LPS), Here, two selected peptides, a 17- and a 19
      mer, were characterized physicochemically and in biological test systems. The
      secondary structure of the peptides indicates essentially a beta-sheet including
      antiparallel strands, the latter being reduced when the peptides bind to LPS. A
      very strong exothermic binding due to attractive Coulomb interactions governs the
      LPS-peptide reaction, which additionally leads to a fluidization of the acyl
      chains of LPS. A comparison of the interaction of the peptide with negatively
      charged phosphatidylserine shows in contrast a rigidification of the acyl chains
      of the lipid. Finally, the biological assays reveal a diverging behaviour of the
      two peptides, with higher antibacterial activity of the 17-mer, but a much higher
      activity of the 19-mer in its ability to inhibit the LPS-induced cytokine
      production in human mononuclear cells.

PMID- 20673225
TI  - The synergistic action of melittin and phospholipase A2 with lipid membranes:
      development of linear dichroism for membrane-insertion kinetics.
AB  - Here we present data on the kinetics of insertion of melittin, a peptide from bee
      venom, into lipid membranes of different composition. Another component of bee
      venom is the enzyme phospholipase A2 (PLA2). We have examined the interaction of
      melittin and PLA2 with liposomes both separately and combined and demonstrate
      that they work synergistically to disrupt the membranes. A dramatic difference in
      the action of melittin and PLA2 is observed when the composition of the membrane
      is altered. Temperature also has a large effect on the kinetics of insertion and
      membrane disruption. We use a combination of techniques to measure liposome size
      (dynamic light scattering), peptide secondary structure (circular dichroism
      spectroscopy), peptide orientation relative to the membrane (linear dichroism
      spectroscopy) and enzymatic digestion of the lipids (mass spectrometry).

PMID- 20673226
TI  - Adsorption and bioactivity of tyrosine hydroxylase on gold surfaces and
      nanoparticles.
AB  - Tyrosine hydroxylase is studied in terms of adsorption behaviour on gold surfaces
      and various passivating layers. Results reveal differences in layer formation,
      where mercaptoundecanoic acid-coated gold shows the best potential in terms of
      adsorbed mass. Nanoparticles with this coating are subsequently tested for
      enzymatic activity, which remains at attenuated levels.

PMID- 20673227
TI  - A Langmuir approach using on monolayer interactions to investigate surface active
      peptides.
AB  - The Langmuir Blodgett apparatus provides a versatile system for studying the
      interfacial properties of peptides and peptide-membrane interactions under
      controlled conditions. Using amphiphilic alpha-helical peptides to highlight
      studies undertaken, here we discuss the use of this system to provide information
      on the surface activity of peptides and describe the insights these studies give
      into biological function.

PMID- 20673228
TI  - Amphipathic antimicrobial peptides--from biophysics to therapeutics?
AB  - Amphipathic peptides are accommodated within the diffuse gradient of polarity
      that characterizes the interfacial regions of phospholipid bilayer membranes.
      Interfacial membrane interactions are key to the diverse biological functions and
      activities of these peptides, which encompass a large class of antimicrobial
      peptides, including the helical peptides magainin, melittin, and RTA3 derived
      from the commensal bacterium Streptococcus mitis. For these peptides in vitro
      efficacy (high antimicrobial activity with minimal mammalian cell toxicity,
      equivalent to high potential therapeutic index; PTI), can be broadly understood
      in relation to the thermodynamics of interfacial binding and membrane disruption
      in membranes having surface charges that correspond to bacterial and mammalian
      cell membranes, respectively. Peptides with disrupted amphipathicity resulting
      from a positively charged amino acid residue on the non-polar helix face, can
      have greatly enhanced PTI, although a balance of amphipathicity, hydrophobicity
      and positive charge is required for retention of high antimicrobial activity.
      These observations are illustrated with recent examples from the literature, and
      studies on RTA3 and magainin analogues from our laboratories. Despite the
      identification and optimisation of peptides with very good PTI, a focus on
      addressing toxicity upon systemic administration and poor in vivo efficacy is
      likely to be required to translate growing understanding of the relationships
      between peptide interfacial activity and effects on cells, into novel systemic
      therapeutics.

PMID- 20673229
TI  - A differential scanning calorimetry study of the effects and interactions of
      antimicrobial peptide LS3 on phosphatidylethanolamine bilayers.
AB  - Differential Scanning Calorimetry studies of a synthetic peptide revealed the
      peptide decreased the temperature of the lamellar-hexagonal phase transition of
      cis-trans mixtures of phosphatidylethanolamine. The transition enthalpy varied
      significantly with lipid composition. The findings are discussed with reference
      to peptide saturation on the bilayer surface, bilayer thinning and peptide
      orientation.

PMID- 20673230
TI  - Antimicrobial and cell-penetrating peptides: structure, assembly and mechanisms
      of membrane lysis via atomistic and coarse-grained molecular dynamics
      simulations.
AB  - Antimicrobial peptides (AMPs) are short, cationic, membrane-interacting proteins
      that exhibit broad-spectrum antimicrobial activity, and are hence of significant
      biomedical interest. They exert their activity by selectively binding to and
      lysing target cell membranes, but the precise molecular details of their
      mechanism are not known. This is further complicated by the fact that their
      structural characteristics are dependent upon the local lipid environment. As a
      result, molecular dynamics (MD) simulations have been applied to understand the
      conformation and mechanism of AMPs, as well as related viral and cell-penetrating
      peptides. In particular, atomically detailed MD simulation studies on the
      timescale of tens to hundreds of nanoseconds have successfully helped to: (i)
      model or refine the conformation of AMPs and their aggregates in the presence of
      membrane-mimicking solvent mixtures, detergent micelles, and lipid bilayers; (ii)
      follow the process of adsorption of individual AMPs to membrane surfaces; and
      (iii) observe the spontaneous assembly of multiple peptides and subsequent
      cooperative membrane lysis. More recently, coarse-grained (CG) models have been
      developed to extend the time and length scales accessible to simulations of
      membrane/peptide systems. CG simulations on the order of microseconds have
      provided insight into AMP lytic mechanisms, and how they depend upon such factors
      as peptide concentration, lipid composition, and bilayer curvature. These studies
      have been supplemented by combined atomistic/CG and integrated multiscale models.
      Together, simulations have deepened our understanding of the interactions between
      AMPs and biological membranes, and will help to design new synthetic peptides
      with enhanced biomedical potential.

PMID- 20673231
TI  - Porcine glutathione transferase Alpha 2-2 is a human GST A3-3 analogue that
      catalyses steroid double-bond isomerization.
AB  - A primary role of GSTs (glutathione transferases) is detoxication of
      electrophilic compounds. In addition to this protective function, hGST (human
      GST) A3-3, a member of the Alpha class of soluble GSTs, has prominent steroid
      double-bond isomerase activity. The isomerase reaction is an obligatory step in
      the biosynthesis of steroid hormones, indicating a special role of hGST A3-3 in
      steroidogenic tissues. An analogous GST with high steroid isomerase activity has
      so far not been found in any other biological species. In the present study, we
      characterized a Sus scrofa (pig) enzyme, pGST A2-2, displaying high steroid
      isomerase activity. High levels of pGST A2-2 expression were found in ovary,
      testis and liver. In its functional properties, other than steroid isomerization,
      pGST A2-2 was most similar to hGST A3-3. The properties of the novel porcine
      enzyme lend support to the notion that particular GSTs play an important role in
      steroidogenesis.

PMID- 20673232
TI  - Pox outbreaks in sheep and goats at Makhdoom (Uttar Pradesh), India: evidence of
      sheeppox virus infection in goats.
AB  - Sheeppox and goatpox outbreaks occur often in India incurring huge economic loss
      to the small ruminant industry. This paper describes two sheeppox outbreaks, of
      which one occurred in an organized sheep breeding farm at Makhdoom (Uttar
      Pradesh), India, during 2007 and another in goats at the Central Institute of
      Research on Goats, Makhdoom (Uttar Pradesh), India during 2008. In the first
      outbreak, a local Muzaffarnagari sheep breed was affected (n=477) with morbidity
      and mortality rates, respectively, of 100% and 53.9% accompanied by significant
      productivity losses. In the 2008 outbreaks, a small number of goats were affected
      without any mortality. The tissue and swabs collected from both the outbreaks
      were processed and inoculated onto Vero cells, and the causative agent of the
      outbreaks, capripox virus (CaPV), was isolated. The identity of the virus was
      confirmed as CaPV based on electron microscopy, experimental pathogenesis in
      sheep, capripox-specific conventional and real-time PCRs. Sequence analysis of
      the P32 envelope protein gene revealed that the causative agent of both outbreaks
      was confirmed as sheeppox virus (SPPV) implying SPPV infection not only in sheep
      but also goats in India.

PMID- 20673233
TI  - Interorgan ammonia metabolism in liver failure: the basis of current and future
      therapies.
AB  - Hepatic encephalopathy complicates the course of both acute and chronic liver
      disease and its treatment remains an unmet clinical need. Ammonia is thought to
      be central in its pathogenesis and remains an important target of current and
      future therapeutic approaches. In liver failure, the main detoxification pathway
      of ammonia metabolism is compromised leading to hyperammonaemia. In this
      situation, the other ammonia-regulating pathways in multiple organs assume
      important significance. The present review focuses upon interorgan ammonia
      metabolism in health and disease describing the role of the key enzymes,
      glutamine synthase and glutaminase. Better understanding of these alternative
      pathways are leading to the development of new therapeutic approaches.

PMID- 20673234
TI  - Social involvement of children with autism spectrum disorders in elementary
      school classrooms.
AB  - BACKGROUND: Children with autism spectrum disorders (ASD) are increasingly
      included in general education classrooms in an effort to improve their social
      involvement. METHODS: Seventy-nine children with ASD and 79 randomly selected,
      gender-matched peers (88.6% male) in 75 early (K-1), middle (2nd-3rd), and late
      (4th-5th) elementary classrooms across 30 schools completed social network
      surveys examining each child's reciprocal friendships, peer rejection,
      acceptance, and social involvement. RESULTS: Across grade levels, peers less
      frequently reciprocated friendships with children with ASD than students in the
      matched sample. While children with ASD were not more likely to be rejected by
      peers, they were less accepted and had fewer reciprocal friendships than matched
      peers at each grade level. Although 48.1% of children with ASD were involved in
      the social networks of their classrooms, children with ASD were more likely to be
      isolated or peripheral to social relationships within the classroom across all
      grade levels, and this difference is even more dramatic in later elementary
      grades. CONCLUSIONS: In inclusive classrooms, children with ASD are only involved
      in peers' social relationships about half of the time, and appear to be even less
      connected with increasing grade level. Promoting children with ASD's skills in
      popular activities to share with peers in early childhood may be a key preventive
      intervention to protect social relationships in late elementary school grades.

PMID- 20673235
TI  - Guild-specific patterns of species richness and host specialization in plant
      herbivore food webs from a tropical forest.
AB  - 1. The extent to which plant-herbivore feeding interactions are specialized is
      key to understand the processes maintaining the diversity of both tropical forest
      plants and their insect herbivores. However, studies documenting the full
      complexity of tropical plant-herbivore food webs are lacking. 2. We describe a
      complex, species-rich plant-herbivore food web for lowland rain forest in Papua
      New Guinea, resolving 6818 feeding links between 224 plant species and 1490
      herbivore species drawn from 11 distinct feeding guilds. By standardizing
      sampling intensity and the phylogenetic diversity of focal plants, we are able to
      make the first rigorous and unbiased comparisons of specificity patterns across
      feeding guilds. 3. Specificity was highly variable among guilds, spanning almost
      the full range of theoretically possible values from extreme trophic
      generalization to monophagy. 4. We identify guilds of herbivores that are most
      likely to influence the composition of tropical forest vegetation through density
      dependent herbivory or apparent competition. 5. We calculate that 251 herbivore
      species (48 of them unique) are associated with each rain forest tree species in
      our study site so that the ~200 tree species coexisting in the lowland rain
      forest community are involved in ~50,000 trophic interactions with ~9600
      herbivore species of insects. This is the first estimate of total herbivore and
      interaction number in a rain forest plant-herbivore food web. 6. A comprehensive
      classification of insect herbivores into 24 guilds is proposed, providing a
      framework for comparative analyses across ecosystems and geographical regions.

PMID- 20673236
TI  - Measurements of foraging success in a highly pelagic marine predator, the
      northern elephant seal.
AB  - 1. Identification of foraging behaviour and the ability to assess foraging
      success is critical to understanding individual and between-species variation in
      habitat use and foraging ecology. For pelagic predators, behaviour-dependent
      foraging metrics are commonly used to identify important foraging areas, yet few
      of these metrics have been validated. 2. Using the northern elephant seal as a
      model species, we validated the use of a behaviour-independent measure of
      foraging success (changes in drift rate) at the scale of the entire foraging
      migration, and then used this to assess a variety of common foraging metrics that
      are based on movement patterns and dive behaviour. Transit rate consistently
      provided the best estimate of daily foraging success, although the addition of
      other metrics provides insight into different foraging behaviours or strategies.
      3. While positive changes in buoyancy occurred throughout most of the migrations,
      implying successful feeding across much of the north Pacific, the areas of most
      rapid changes in buoyancy occurred along a latitudinal band (40-50 degrees  N)
      corresponding to a dynamic hydrographic region including Subarctic Gyre and
      Transition Zone waters. 4. These results support the use of transit rate as an
      index of foraging success: a metric that is easily derived from tracking
      measurements on a wide range of marine species.

PMID- 20673237
TI  - Interleukin-9 as a T helper type 17 cytokine.
AB  - The production of interleukin-9 (IL-9) by CD4 T cells has gathered renewed
      interest as the result of the observation that its expression is broader than
      originally thought. This includes the production of IL-9 by a recently
      characterized subset of CD4 helper T (Th) cells that are termed Th9 as well as
      production by additional T-cell subsets including Th17 cells. There is an
      incomplete understanding as to which IL-9-producing T-cell subsets develop under
      physiological conditions. We describe the conditions used to generate IL-9 in
      Th17 cells in vitro. We also summarize conditions where both IL-9 and IL-17 are
      found in vivo and propose that Th17 cells producing IL-9 may co-exist and
      interact with Th9 cells during conditions of autoimmunity, allergy and infection.

PMID- 20673238
TI  - Natural killer cells support the induction of protective immunity during
      dendritic cell-mediated vaccination against Leishmania major.
AB  - Dendritic cell (DC)-mediated vaccination against Leishmania major induces a
      parasite-specific T helper 1 (Th1) response and long-lasting protective immunity
      in susceptible mice. As the cytokine interleukin-12 required for induction of
      this Th1 response is not derived from the transferred DC, but has to be produced
      by the vaccinated host, we examined cross-presentation of transferred DC via
      resident DC of the host and cross-activation with natural killer (NK) cells as
      mechanisms supporting the induction of protective immunity after DC-mediated
      vaccination. Co-culture with DC that had been conditioned ex vivo by loading with
      L. major lysate and stimulation with CpG-containing oligodeoxynucleotides did not
      result in the activation of naive DC in vitro. Furthermore, L. major antigen from
      conditioned DC was not cross-presented to a significant extent in vivo. In
      contrast, co-culture of DC with NK cells led to cross-activation of both cell
      populations with induction of interferon-gamma, which was dependent on the
      activation status of the conditioned DC. Transient depletion of NK cells during
      vaccination of L. major-susceptible mice with conditioned DC resulted in reduced
      protection. Our findings indicate that cross-presentation of conditioned DC after
      DC-based vaccination against L. major plays a minor role in the induction of
      protective immunity. However, we demonstrated for the first time that the
      capacity of DC to mediate protection against L. major is supported by cross
      activation with NK cells of the host and NK-cell-derived interferon-gamma.

PMID- 20673239
TI  - Maternally transferred anti-factor VIII IgG reduce the anti-factor VIII humoral
      immune response in factor VIII-deficient mice.
AB  - Replacement therapy with exogenous factor VIII (FVIII) to treat haemorrhages or
      used in prophylaxis induces inhibitory anti-FVIII immunoglobulin G (IgG) in some
      patients with haemophilia A. Therapeutic strategies to prevent the onset of the
      deleterious anti-FVIII immune response are still lacking. Maternal IgG is
      transferred to the offspring during fetal and neonatal life. While protecting the
      offspring from bacterial and viral infections, maternal IgG may alter the
      repertoires of T and B lymphocytes, and may impair vaccination in early infancy.
      Using haemophilic mice, we demonstrate that the transfer of maternal anti-FVIII
      IgG modulates the onset of anti-FVIII inhibitory IgG in early adulthood. The
      protective effect is reproduced upon reconstitution of naive mice with anti-FVIII
      IgG, suggesting that the reduced ability to mount an anti-FVIII immune response
      is the result of an interference between circulating anti-FVIII IgG and the
      administered FVIII rather than to a profound remodelling of lymphocyte
      repertoires occurring during the ontogeny of the immune system.

PMID- 20673240
TI  - Interleukin-7 enhances memory CD8(+) T-cell recall responses in health but its
      activity is impaired in human immunodeficiency virus infection.
AB  - Memory CD8(+) T cells regain function during a recall response, but the
      requirement of signals in addition to antigen during a secondary immune response
      is unknown. In this study, the ability of interleukin-7 (IL-7) to enhance memory
      CD8(+ ) CD45RA(- ) CD127(+) T-cell responses in health and in human
      immunodeficiency virus (HIV) infection was investigated. CD8(+) T-cell-depleted
      peripheral blood mononuclear cells (PBMCs) from HIV(-) and untreated HIV(+)
      donors were pulsed with a cytomegalovirus/Epstein-Barr virus/influenza (CEF)
      peptide pool, and co-cultured with autologous memory CD8(+) T cells in the
      presence of IL-7. Cell survival and the function of memory CD8(+) T-cell subsets
      were then evaluated. Memory CD8(+) T-cell proliferation and interferon-gamma (IFN
      gamma) production was enhanced by the presence of antigen, and the addition of IL
      7 further enhanced antigen-induced proliferation. In HIV(+) individuals, the
      presence of antigen enhanced IFN-gamma production to a small degree but did not
      enhance proliferation. Lastly, IL-7 did not enhance antigen-mediated
      proliferation of memory CD8(+) T cells from HIV(+) individuals. IL-7 therefore
      appears to have a role in secondary immune responses and its activity is impaired
      in memory CD8(+) T cells from HIV(+) individuals. These results further our
      understanding of the signals involved in secondary immune responses, and provide
      new insight into the loss of CD8(+) T-cell function in HIV infection.

PMID- 20673241
TI  - Innate immune stimuli modulate bone marrow-derived dendritic cell production in
      vitro by toll-like receptor-dependent and -independent mechanisms.
AB  - Haematopoiesis is crucial for immunity because it results in the production of
      leucocytes. Bacterial and viral infections alter leucocyte production by
      promoting granulopoiesis or lymphopoiesis. Recent studies suggest that changes in
      leucocyte production may be caused by the effects of inflammatory responses on
      the differentiation of haematopoietic progenitors in the bone marrow. We
      investigated the mechanisms through which infection regulates the formation of
      bone marrow-derived dendritic cells (BMDCs) in vitro. We mimicked infection by
      stimulating developing cells with molecules associated with bacteria and viruses
      and with inactivated influenza viruses. We showed that toll-like receptor (TLR)
      ligands act as modulators of haematopoiesis, and that signalling through
      different TLRs results in differing effects on the production of BMDCs. We
      demonstrated that ligands for TLR3 and influenza viruses reduce the production of
      BMDCs, resulting in increased neutrophil numbers, and that ligands for TLR4 and
      TLR9 drive the production of plasmacytoid dendritic cells. Furthermore, there are
      distinct signalling mechanisms involved in these effects. Signalling pathways
      triggered by TLR4 and TLR9 involve MyD88 and are partially mediated by the
      cytokine tumour necrosis factor-alpha (TNF-alpha). Mechanisms activated by TLR3
      were Tir-domain-containing adaptor-inducing interferon dependent. Haematopoietic
      modulation induced by inactivated influenza viruses was associated with the
      activation of an antiviral pathway mediated by type-1 interferons.

PMID- 20673242
TI  - Exploring the influence of service user involvement on health and social care
      services for cancer.
AB  - BACKGROUND: Service user involvement in health and social care is a key policy
      driver in the UK. In cancer care it is central to developing services which are
      effective, responsive and accessible to patients. Cancer network partnership
      groups are set up to enable joint working between service users and health care
      professionals and to drive service improvements. AIMS AND OBJECTIVES: The aim of
      this study was to explore the influence of the cancer network partnership groups'
      service user involvement activities on cancer care. DESIGN: This was a
      qualitative study involving documentary analysis and in-depth case studies of a
      sample of partnership groups. SETTING AND PARTICIPANTS: Five partnership groups
      were purposively selected as case studies from Macmillan regions across the UK;
      documents were collated from a further five groups. Forty people, including core
      group members and key stakeholders in cancer services, were interviewed. RESULTS
      AND CONCLUSIONS: The evidence from this study suggests that cancer network
      partnership groups are at their most influential at 'grass roots' level -
      contributing to patient information resources, enhancing access to services, and
      improving care environments. While such improvements are undoubtedly important to
      patients, the groups' aim is to influence strategic changes, for example in
      cancer care commissioning or macro-level policy decision-making. The evolution of
      open, participatory relationships between service users and professionals, and
      recognition of the value of experiential knowledge are seen as key factors in
      influencing cancer care. The provision of dedicated resources to strengthen
      service user involvement activities is also vital.

PMID- 20673243
TI  - Demands for 'off-licence' access to trastuzumab (Herceptin): content analysis of
      UK newspaper articles.
AB  - BACKGROUND: Sensationalized reporting styles and a distorted framing of health
      care issues in newspapers may trigger inappropriate commissioning decisions. We
      evaluated UK press coverage of pre-licensing access to trastuzumab (Herceptin)
      for early breast cancer as a case study. METHODS AND FINDINGS: Content analysis
      of newspaper articles published between April 2005 and May 2006 were coded by two
      researchers for interest groups represented, claims made and sensationalized
      reporting. Disagreements in coding were resolved by a third researcher. One
      thousand and ninety published articles were identified in the study period and a
      20% sample (n = 218) was included in the content analysis. Most articles (76%,
      95% CI 71-82) included claims about the clinical benefits of trastuzumab, and
      this was significantly higher than those expressing the uncertainty surrounding
      such benefits (6%, 95% CI 3-9) or those that discussed the potential harms (5%,
      95% CI 2-8). Articles were significantly more likely to feature claims made by a
      breast cancer survivor or family member than any other interest group (P <
      0.0001). Almost half of the articles carried some message to the effect that
      trastuzumab would make the difference between life and death (47%, 95% CI 40-53).
      Over a quarter (28%, 95% CI 22-34) suggested that trastuzumab is a 'miracle drug'
      or similar. CONCLUSIONS: The benefits of drugs are highlighted, frequently using
      sensationalist language, without equal consideration of uncertainty or risks.
      Health-care purchasers should express decisions in opportunity cost terms;
      journalists should give fairer coverage to such arguments.

PMID- 20673245
TI  - The use of the mechanical fragility test in evaluating sublethal RBC injury
      during storage.
AB  - BACKGROUND: The mechanical fragility index (MFI) is an in vitro measurement of
      the extent of RBC sublethal injury. Sublethal injury might constitute a component
      of the RBC storage lesion, thus the MFI was determined serially during routine
      RBC storage. METHODS: Leucoreduced AS-5- and SAGM-preserved RBCs were stored
      under routine blood bank conditions. The mechanical fragility (MF) of each unit
      was serially measured during storage. RESULTS: For both AS-5 and SAGM units, male
      and female RBCs demonstrated statistically significant increases in the MFI
      during storage. The MFI was significantly lower in AS-5 units compared to SAGM
      units throughout storage. Female RBCs had significantly lower MFI vs. male RBCs
      in both AS-5 and SAGM units at all times. No significant differences in MFI were
      observed between ABO groups for both genders for AS-5 RBCs. CONCLUSIONS: The MF
      of RBCs increases during storage. Both gender and preservation solution
      influenced the MFI; however, the male:female MFI ratios were similar at all time
      points and remained stable, suggesting that gender-based biological differences
      exist independent of storage solution. The MF could be a useful test for
      evaluating the effect of novel interventions intended to mitigate the
      susceptibility of RBCs to sublethal injury during storage.

PMID- 20673244
TI  - Patient-physician agreement on the content of CHD prevention discussions.
AB  - BACKGROUND: Little is known about agreement between patients and physicians on
      content and outcomes of clinical discussions. A common perception of content and
      outcomes may be desirable to optimize decision making and clinical care.
      OBJECTIVE: To determine patient-physician agreement on content and outcomes of
      coronary heart disease (CHD) prevention discussions. DESIGN: Cross-sectional
      survey nested within a randomized CHD prevention study. SETTING AND PARTICIPANTS:
      University internal medicine clinic; 24 physicians and 157 patients. METHODS:
      Following one clinic visit, we surveyed patients and physicians on discussion
      content, decision making and final decisions about CHD prevention. For
      comparison, we audio-recorded, transcribed and coded 20 patient-physician visits.
      We calculated percent agreement between patient/physician reports,
      patient/transcription reports and physician/transcription reports. We calculated
      Cohen's kappas to compare patient/physician perspectives. RESULTS: Patients and
      physicians agreed on whether CHD was discussed in 130 visits (83%; kappa = 0.55;
      95% CI 0.40-0.70). When discussions occurred, they agreed about discussion
      content (pros versus cons) in 53% of visits (kappa = 0.15; 95% CI -0.01-0.30) and
      physicians' recommendations in 73% (kappa = 0.44; 95% CI 0.28-0.66). Patients and
      physicians agreed on final decisions to take medication in 78% (kappa = 0.58; 95%
      CI 0.45-0.71) and change lifestyle in 69% (kappa = 0.38; 95% CI 0.24-0.53). They
      agreed less often, 43% (kappa = 0.13; 95% CI -0.11-0.37) about degree of
      involvement in decision making. Audio-recorded results were similar, but showed
      very low agreement between transcripts and patients' and physicians' self-report
      on discussion content and decision making. CONCLUSIONS: Disagreements about
      clinical discussions and decision making may be common. Future work is needed to
      determine: how widespread such agreements are; whether they impact clinical
      outcomes; and the relative importance of the subjective experience versus
      objective steps of shared decision making.

PMID- 20673246
TI  - Comparison of acupuncture to injection for myofascial trigger point pain.
AB  - OBJECTIVES: Many treatments have been proposed for myofascial pain syndrome. The
      objective of this study was to compare the analgesic effect of acupuncture to
      trigger point injection combined with cyclobenzaprine chlorhydrate and sodium
      dipyrone. METHODS: A randomized study was performed in 30 patients divided into 2
      groups: G1 received trigger point injection with 0.25% bupivacaine twice weekly,
      and both cyclobenzaprine chlorhydrate 10 mg/day and sodium dipyrone 500 mg every
      8 hours; G2 received classical and trigger point acupuncture twice weekly. All
      patients were instructed in physical exercise. The following parameters were
      evaluated: pain intensity rated on a numerical scale, number of trigger points,
      and quality of life before and 4 weeks after treatment. RESULTS: The pain scores
      and the number of trigger points reduced significantly in both groups, with no
      significant difference between groups. Significant improvement in the quality of
      life scores was observed for some of the functional domains in the 2 groups,
      whereas there was no improvement of the general health status domain in either
      group or of the emotional domain in G1. CONCLUSION: Acupuncture, when compared
      with trigger point injection, combined with cyclobenzaprine chlorhydrate and
      sodium dipyrone provided similar pain relief and improvement in quality of life
      measures at 4 weeks. 

PMID- 20673247
TI  - What are the validated animal models for tendinopathy?
AB  - Chronic tendinopathy refers to a broad spectrum of pathological conditions in
      tendons and their insertion, with symptoms including activity-related chronic
      pain. To study the pathogenesis and management strategies of chronic
      tendinopathy, studies in animal models are essential. The different animal models
      in the literature present advantages and limitations, and there is no consensus
      regarding the criteria of a universal tendinopathy animal model. Based on the
      review of literature and the discussion in the International Symposium on
      Ligaments and Tendons-X, we concluded that established clinical,
      histopathological and functional characteristics of human tendinopathy were all
      important and relevant criteria to be met, if possible, by animal models. As
      tendinopathy is a progressive, multifactorial tendon disorder affecting different
      anatomical structures, it may not be realistic to expect a single animal model to
      study all aspects of tendinopathy. Staging of tendinopathy over time and clearer
      definition of tendinopathies in relation to severity and type would enable
      realistic targets with any animal model. The existing animal models can be used
      for answering specific questions (horses for courses) but should not be used to
      conclude the general aspects of tendinopathy neither in animals nor in human.

PMID- 20673248
TI  - Biomechanical responses of different rat tendons to nandrolone decanoate and load
      exercise.
AB  - Androgenic-anabolic steroids (AAS) have been associated with an increased
      incidence of tendon rupture. The aim of this study was to compare the
      biomechanical properties of the rat calcaneal tendon (CT), superficial flexor
      tendon (SFT), and deep flexor tendon (DFT), and to determine the effect of jump
      training in association with AAS. Animals were separated into four groups:
      sedentary, trained, AAS-treated sedentary rats (AAS), and AAS-treated and trained
      animals. Mechanical testing showed that the CT differed from the DFT and SFT,
      which showed similar mechanical properties. Jump caused the CT to exhibit an
      extended toe region, an increased resistance to tensional load, and a decreased
      elastic modulus, characteristics of an elastic tendon capable of storing energy.
      AAS caused the tendons to be less compliant, and the effects were reinforced by
      simultaneous training. The DFT was the most affected by training, AAS, and the
      interaction of both, likely because of its involvement in the toe-off step of
      jumping, which we suggest is related to the rapid transmission of force as
      opposed to energy storage. In conclusion, tendons are differently adapted to
      exercise, but responded equally to AAS, showing reduced flexibility, which is
      suggested to increase the risk of tendon rupture in AAS consumers.

PMID- 20673249
TI  - Knee laxity after complete anterior cruciate ligament tear: a prospective study
      over 15 years.
AB  - There is limited knowledge of knee laxity in the long term after a complete
      anterior cruciate ligament (ACL) tear treated without ACL reconstruction. The aim
      of this study was (1) to describe the clinical course of knee laxity after a
      complete ACL tear over 15 years, and (2) to study the association between knee
      laxity and meniscal injuries and the development of knee osteoarthritis (OA). We
      studied 100 consecutive subjects [mean (SD) age 26 (8) years] presenting with
      acute ACL injury prospectively. The initial treatment in all subjects was knee
      rehabilitation without reconstructive surgery. The subjects were examined with
      Lachman's and pivot-shift tests at baseline, 6 weeks, 3 months, 1 year, 3 years
      and 15 years after the injury. Sagittal knee laxity was also evaluated with the
      KT-1000 arthrometer at the 15-year follow-up. During follow-up, 22 subjects were
      ACL reconstructed due to unacceptable knee instability. There was only a mild
      remaining knee laxity [median Lachman grade and pivot-shift test value of 1 on a
      4-grade scale (0-3)] after 15 years in subjects treated without primary ACL
      reconstruction. Knees with higher anterior sagittal knee laxity 3 months after
      the injury had a worse long-term outcome with respect to meniscal injuries and
      knee OA development.

PMID- 20673250
TI  - Early E-modulus of healing Achilles tendons correlates with late function:
      similar results with or without surgery.
AB  - Non-operative treatment of Achilles tendon ruptures is associated with an
      increased risk of rerupture. We hypothesized that this is due to inferior
      mechanical properties during an early phase of healing, and performed a
      randomized trial, using a new method to measure the mechanical properties.
      Tantalum markers were inserted in the tendon stumps, and tendon strain at
      different loadings was measured by stereo-radiography (Roentgen
      stereophotogrammetric analysis) at 3, 7 and 19 weeks and 18 months after injury.
      Thirty patients were randomized to operative or non-operative treatment. The
      primary out-come variable was an estimate for the modulus of elasticity at 7
      weeks. Strain per force, cross-sectional area and tendon elongation were also
      measured. The functional outcome variable was the heel-raise index after 18
      months. There was no difference in the mean modulus of elasticity or other
      mechanical or functional variables between operative and non-operative treatments
      at any time-point, but strain per force at 7 and 19 weeks had a significantly
      larger variation in the non-operative group. This group, therefore, might contain
      more outliers with poor healing. The modulus of elasticity at 7 weeks correlated
      with the heel-raise index after 18 months in both treatment groups (r(2) =0.75;
      P=0.0001). This correlation is an intriguing finding.

PMID- 20673251
TI  - Aerobic training at moderate intensity reduced protein oxidation in adolescents
      with Down syndrome.
AB  - Individuals with Down syndrome have been generally described as having high
      levels of oxidative stress, which have been associated to an increased morbidity.
      Fortunately, recent studies have reported that aerobic training may upregulate
      antioxidant defence system both in general population and individuals with
      trisomy 21. Accordingly, the present study was conducted to ascertain the
      effectiveness of aerobic training in reducing protein oxidation. To achieve this
      goal, 31 adolescents with Down syndrome performed a 12-week training program on a
      treadmill with 3 days/week, consisting of warm-up (15 min), main part (20-35 min)
      at a work intensity of 60-75% of peak heart rate (HR(max) =194.5-[0.56 age]) and
      cool-down (10 min). A control group included seven age-, sex- and BMI-matched
      adolescents with trisomy 21 that did not perform any training program. Plasma
      carbonyl content was determined by means of a slightly modified Levine method.
      Pre- and post-training carbonyl contents were 1.98 +/- 0.2 [95% confidence
      intervals (95% CI): 1.94-2.02] nmol/mg protein and 1.16 +/- 0.1 (95% CI: 1.14
      1.18) nmol/mg protein, respectively. When compared with baseline values, it was
      decreased significantly (1.98 +/- 0.2 vs 1.16 +/- 0.1; P<0.001). It was concluded
      that 12-week exercise program significantly reduced protein oxidation in
      adolescents with Down syndrome. Further long-term follow-up studies are required
      to determine whether correction of this oxidant imbalance improves clinical
      outcomes of individuals with trisomy 21.

PMID- 20673252
TI  - Effect of N-acetylcysteine on markers of skeletal muscle injury after fatiguing
      contractile activity.
AB  - The effects of N-Acetylcysteine (NAC), an unspecific antioxidant, on fatiguing
      contractile activity-induced injury were investigated. Twenty-four male Wistar
      rats were randomly assigned to two groups. The placebo group (N=12) received one
      injection of phosphate buffer (PBS) 1 h prior to contractile activity induced by
      electrical stimulation. The NAC group (NAC; N=12) received electrical stimulation
      for the same time period and NAC (500 mg/kg, i.p.) dissolved in PBS 1 h prior to
      electrical stimulation. The contralateral hindlimb was used as a control, except
      in the analysis of plasma enzyme activities, when a control group (rats placebo
      group not electrically stimulated and not treated) was included. The following
      parameters were measured: tetanic force, muscle fatigue, plasma activities of
      creatine kinase (CK) and lactate dehydrogenase (LDH), changes in muscle vascular
      permeability using Evans blue dye (EBD), muscle content of reactive oxygen
      species (ROS) and thiobarbituric acid-reactive substances (TBARS) and
      myeloperoxidase (MPO) activity. Muscle fatigue was delayed and tetanic force was
      preserved in NAC-treated rats. NAC treatment decreased plasma CK and LDH
      activities. The content of muscle-derived ROS, TBARS, EBD and MPO activity in
      both gastrocnemius and soleus muscles were also decreased by NAC pre-treatment.
      Thus, NAC has a protective effect against injury induced by fatiguing contractile
      activity in skeletal muscle.

PMID- 20673253
TI  - Sever's injury; treat it with a heel cup: a randomized, crossover study with two
      insole alternatives.
AB  - Sever's injury (apophysitis calcanei) is considered to be the dominant cause of
      heel pain among children. Common advice is to reduce physical activity. However,
      our previous study showed that application of insoles reduced pain in Sever's
      injury without having to reduce physical activity. The purpose of this study was
      to test which of the two insoles, the heel wedge or the heel cup, provided best
      pain relief during sport activity in boys with Sever's injury (n=51). There was a
      crossover design in the first randomized part of the study. In the second part,
      the boys, 9-14 years, chose which insole they preferred. There was a reduction in
      odds score for pain to a fifth (a reduction of 80%) for the cup compared with the
      wedge (P<0.001). When an active choice was made, the heel cup was preferred by
      >75% of the boys. All boys maintained their high level of physical activity
      throughout. At 1-year follow-up, 22 boys still used an insole and 19 of them
      reported its effect on pain as excellent or good (n=41).

PMID- 20673255
TI  - An intense and unforgettable experience: the lived experience of malignant wounds
      from the perspectives of patients, caregivers and nurses.
AB  - Malignant wounds occur infrequently, but are typically described as devastating
      and overwhelming. However, there has been little formalised research, and the
      vast majority of existing malignant wound literature comprises reports of health
      care professionals from their management of the physical symptoms. Few studies
      have investigated the lived experience from the perspectives of patients and
      nurses and none have investigated the experiences of lay caregivers caring for a
      patient with a malignant wound. As a result, there has been little mention in
      existing literature of the non physical issues associated with malignant wounds
      or how they might be addressed. The purpose of this study was to address this gap
      in knowledge by investigating the lived experience of malignant wounds from the
      perspectives of those living it. In-depth interviews were conducted with
      patients, caregivers and nurses. The data were analysed thematically within a
      hermeneutic phenomenological methodology to show four themes: (i) malodour; (ii)
      new mode of being-in-the-world; (iii) still room for hope and (iv) enduring
      memories. Although this study confirmed previous findings that malodour was one
      of the worst aspects of malignant wounds, it was significant that the other three
      themes occurred in the previously largely overlooked psychosocial domain.

PMID- 20673256
TI  - Impact of gauze-based NPWT on the patient and nursing experience in the treatment
      of challenging wounds.
AB  - Negative pressure wound therapy is widely used in the treatment of hard-to-heal
      wounds; however, pain during dressing changes, which is often associated with
      pain on the commencement and cessation of pressure application and because of in
      growth of new granulation tissue into interstices of foam dressings, is often
      experienced. Anecdotal reports have suggested that choice of gauze as the
      negative pressure wound therapy dressing may reduce the pain associated with
      dressing changes. A prospective, multi-center, non-comparative clinical
      investigation was carried out using gauze-based negative pressure wound therapy
      in chronic and acute wounds. Over 152 patients were evaluated. Median duration of
      therapy was 18 days with 91% of patients progressing towards healing at the end
      of therapy. Wound pain and odour were significantly reduced (P < 0.001) over the
      course of therapy. Wound pain during dressing changes was reported to be absent
      in 80% of dressing removals. No damage to the wound bed following dressing
      removal was observed in 96% of dressing changes. Dressing applications were
      considered easy in 79% of assessments and took a median of 20 min to complete. In
      patients susceptible to pain, gauze-based negative pressure therapy may be a
      viable option to maximise patient comfort.

PMID- 20673254
TI  - Dietary assessment of individuals with chronic kidney disease.
AB  - Examining the quality and quantity of food intake by appropriate methods is
      critical in the management of patients with chronic kidney disease (CKD). The
      four commonly used dietary assessment methods in CKD patients include short-term
      dietary recalls, several days of food records with or without dietary interviews,
      urea kinetic based estimates such as protein nitrogen appearance calculation, and
      food histories including food screeners and food frequency questionnaires (FFQ).
      There are a number of strengths and limitations of these dietary assessment
      methods. Accordingly, none of the four methods is suitable in and of itself to
      give sufficiently accurate dietary information for all purposes. Food frequency
      questionnaires, which is the preferred method for epidemiological studies, should
      be used for dietary comparisons of patients within a given population rather than
      individual assessment. Food histories including FFQ and dietary recalls may
      underestimate important nutrients, especially in CKD patients. Given the large
      and increasing number of dialysis patients and work responsibilities of renal
      dietitians, routine analysis of dietary records and recalls is becoming less
      feasible. Ongoing and future studies will ascertain additional strengths and
      limitations of dietary assessment methods in CKD populations including the
      assessment of food intake during an actual hemodialysis treatment.

PMID- 20673257
TI  - Estimating the impact of healthcare-associated infections on length of stay and
      costs.
AB  - Healthcare-associated infections (HAIs) unquestionably have substantial effects
      on morbidity and mortality. However, quantifying the exact economic burden
      attributable to HAIs still remains a challenging issue. Inaccurate estimations
      may arise from two major sources of bias. First, factors other than infection may
      affect patients' length of stay (LOS) and healthcare utilization. Second, HAI is
      a time-varying exposure, as the infection can impact on LOS and costs only after
      the infection has started. The most frequent mistake in previously published
      evidence is the introduction of time-dependent information as time-fixed, on the
      assumption that the impact of such exposure on the outcome was already present on
      admission. Longitudinal and multistate models avoid time-dependent bias and
      address the time-dependent complexity of the data. Appropriate statistical
      methods are important in analysis of excess costs and LOS associated with HAI,
      because informed decisions and policy developments may depend on them.

PMID- 20673258
TI  - Understanding cost-effectiveness.
AB  - Healthcare delivery in the USA and abroad has changed dramatically over the last
      several decades. Along with the growth in diagnostic and therapeutic
      interventions, the costs of healthcare have escalated out of proportion relative
      to other aspects of the economy. This growth has fostered careful scrutiny of
      both the effectiveness and efficiency of healthcare delivery. Because of this
      emphasis on the economics of healthcare, physicians require an understanding not
      only of the efficacy and clinical utility of their interventions, but also of the
      relative value in an economic sense of their efforts. In other words, physicians
      in the modern era must now appreciate the concept of cost-effectiveness. Cost
      effectiveness and cost-utility analyses are critical evaluative tools. Explicit
      data on comparative cost-effectiveness are useful for allocating the increasingly
      stretched healthcare resources. This article provides a primer for understanding
      the methods and applications of cost-effectiveness and cost-utility analyses.

PMID- 20673259
TI  - Balancing the benefits and costs of antibiotic drugs: the TREAT model.
AB  - TREAT is a computerized decision support system aimed at improving empirical
      antibiotic treatment of inpatients with suspected bacterial infections. It
      contains a model that balances, for each antibiotic choice (including 'no
      antibiotics'), expected benefit and expected costs. The main benefit afforded by
      appropriate, empirical, early antibiotic treatment in moderate to severe
      infections is a better chance of survival. Each antibiotic drug was consigned
      three cost components: cost of the drug and administration; cost of side effects;
      and costs of future resistance. 'No treatment' incurs no costs. The model worked
      well for decision support. Its analysis showed, yet again, that for moderate to
      severe infections, a model that does not include costs of resistance to future
      patients will always return maximum antibiotic treatment. Two major moral
      decisions are hidden in the model: how to take into account the limited life
      expectancy and limited quality of life of old or very sick patients; and how to
      assign a value for a life-year of a future, unnamed patient vs. the present,
      individual patient.

PMID- 20673260
TI  - Resistant viral variants in cellular reservoirs of human immunodeficiency virus
      infection.
AB  - Since the advent of antiretroviral therapy (ART), morbidity and mortality rates
      in those infected with human immunodeficiency virus type 1 (HIV-1) have been
      significantly reduced. However, HIV-1 is known to persist in several types of
      cells and tissues, and will usually return to pretreatment levels when therapy is
      stopped, even in those individuals who have been on suppressive ART for a long
      time. The discovery of drug sanctuaries and viral reservoirs in the body, in
      which HIV may persist, has helped to explain why therapeutic eradication of HIV-1
      has proved so difficult. Several studies have indicated that the latent reservoir
      is an archive, composed of a mixture of wild-type and drug-resistant strains.
      Archived variants are assumed to remain life-long, thereby precluding the
      successful recycling of any drug towards which resistance has arisen. Several
      studies have underlined the value of pro-viral DNA as an additional source of
      information on the total burden of resistance in an individual. The HIV mutation
      patterns detected in plasma do not necessarily reflect those found in the cell
      associated compartment, and may not be the same as those in different anatomical
      compartments. Although assessment of drug resistance in plasma is of direct and
      immediate importance for treatment, examination of the genotypic pattern of HIV-1
      in cellular compartments might also provide information allowing a more
      sustainable response to therapy and better disease management.

PMID- 20673261
TI  - Accuracy of the API Campy system, the Vitek 2 Neisseria-Haemophilus card and
      matrix-assisted laser desorption ionization time-of-flight mass spectrometry for
      the identification of Campylobacter and related organisms.
AB  - Biochemical identification of Campylobacter and related organisms is not always
      specific, and may lead to diagnostic errors. The API Campy, the Vitek 2 system
      and matrix-assisted desorption ionization time-of-flight mass spectrometry (MALDI
      TOF MS) are commercially available methods that are routinely used for the
      identification of these microorganisms. In the present study, we used 224
      clinical isolates and ten reference strains previously identified by multiple PCR
      assays, whole cell protein profiling and either DNA-DNA hybridization or
      sequencing analysis to compare the reliability of these three methods for the
      identification of Campylobacter and related pathogens. The API Campy accurately
      identified 94.4% of Campylobacter jejuni ssp. jejuni and 73.8% of Campylobacter
      coli, but failed to correctly identify 52.3% of other Epsilobacteria. The Vitek 2
      Neisseria-Haemophilus card correctly identified most C. jejuni ssp.jejuni (89.6%)
      and C. coli (87.7%) strains, which account for the majority of campylobacterioses
      reported in humans, but it failed in the identification of all of the other
      species. Despite a good identification rate for both C. jejuni ssp. jejuni and C.
      coli, both methods showed poor sensitivity in the identification of related
      organisms, and additional tests were frequently needed. In contrast to API Campy
      and Vitek, MALDI-TOF MS correctly identified 100% of C. coli and C. jejuni
      strains tested. With an overall sensitivity of 98.3% and a short response time,
      this technology appears to be a reliable and promising method for the routine
      identification of Campylobacter and other Epsilobacteria.

PMID- 20673262
TI  - Seasonal variation in Escherichia coli bloodstream infections in northern Israel.
AB  - Seasonal variation in the infection rate with certain Gram-negative organisms has
      been previously described, but few studies have been published regarding
      Escherichia coli. The aim of this study was to investigate the incidence rate of
      E. coli bloodstream infection (BSI) and the association with temperature in
      different seasons in the Yizrael Valley. Positive blood cultures sent to the
      microbiology laboratory of Ha'Emek Medical Centre over a period of 8 years
      (January 2001 to December 2008) were included. The mean monthly temperature in
      the Yizrael Valley in the same period was compared with the monthly E. coli BSI
      rate. We divided the year into three periods: winter (December to February: mean
      temperature <15 degrees C), transitional (March, April and November: mean
      temperature 15-19 degrees C) and summer (May to October: mean temperature >=20
      degrees C). In addition, we correlated the mean monthly antibiotic use in the
      same period measured as total defined daily doses for the whole regional
      population with E. coli BSI. During the study period, 2810 BSIs were recorded
      (35%E. coli). In 67.4% of the cases of E. coli bacteraemia, the source was
      urinary tract infection. The crude incidence of E. coli BSI was 4.1/1000
      admissions. There was no difference in the number of cultures/month (mean: 29 +/-
      6). However, E. coli BSI was 19% and 21% more frequent in summer than in the
      transitional and winter seasons, respectively (p 0.01). The antibiotic
      consumption was significantly higher in the winter period. We found significantly
      higher rates of E. coli BSI in the summer period. Host, bacterial and ecological
      factors, together with high consumption of antibiotics during the winter season,
      could partially explain these findings.

PMID- 20673263
TI  - Suppressor of cytokine signaling-3 is affected in T-cells from tuberculosisTB
      patients.
AB  - T-cells and T-cell-derived cytokines are crucial mediators of protection against
      Mycobacterium tuberculosis infection, but these factors are insufficient as
      biomarkers for disease susceptibility. In order to define T-cell molecules
      involved in tuberculosis (TB), we compared gene expression profiles of T-cells
      from patients with active TB, healthy donors with latent M. tuberculosis
      infection (LTBIs) and non-infected healthy donors (NIDs) by microarray analysis.
      Pathway-focused analyses identified a prevalent subset of candidate genes
      involved in the Janus kinase (JAK)-signal transducer and activator of
      transcription signalling pathway, including those encoding suppressor of cytokine
      signalling (SOCS) molecules, in the subset of protection-associated genes.
      Differential expression was verified by quantitative PCR analysis for the
      cytokine-inducible SH2-containing protein (CISH), SOCS3, JAK3, interleukin-2
      receptor alpha-chain (IL2RA), and the proto-oncogene serine/threonine protein
      kinase (PIM1). Classification analyses revealed that this set of molecules was
      able to discriminate efficiently between T-cells from TB patients and those from
      LTBIs, and, notably, to achieve optimal discrimination between LTBIs and NIDs.
      Further characterization by quantitative PCR revealed highly variable candidate
      gene expression in CD4(+) and CD8(+) T-cells from TB patients and only minor
      differences between CD4(+) and CD8(+) T-cell subpopulations. These results point
      to a role of cytokine receptor signalling regulation in T-cells in susceptibility
      to TB.

PMID- 20673264
TI  - Lack of evidence for persistent nasal colonization with community-acquired
      methicillin-resistant Staphylococcus aureus in a central European cohort.
AB  - One hundred and three patients who had previously tested positive for community
      acquired methicillin-resistant Staphylococcus aureus (cMRSA) were followed up for
      a mean time of 32.6 months. Eighty patients had a history of skin or soft tissue
      infection, and the remainder were mostly asymptomatic carriers. Of 103 patients,
      only two reported ongoing symptoms with abscess formation. Of 81 nasal swabs
      available, 30.9% were positive for S. aureus but only four yielded Panton
      Valentine leukocidin-positive methicillin-resistant S. aureus. In summary, we
      were unable to find persistent health issues or nasal colonization with cMRSA in
      a cohort of previously cMRSA-infected/colonized patients.

PMID- 20673265
TI  - Cost-effectiveness of adding decolonization to a surveillance strategy of
      screening and isolation for methicillin-resistant Staphylococcus aureus carriers.
AB  - We compared the cost-effectiveness of a methicillin-resistant Staphylococcus
      aureus (MRSA) programme of active surveillance plus decolonization with the
      current Veterans Health Administration (VHA) strategy of active surveillance
      alone, as well as a common strategy of no surveillance. A decision-analytical
      model was developed for an inpatient stay time horizon, using the VHA's
      perspective. Model inputs were taken from published literature where available,
      and supplemented with expert opinion when necessary. Effectiveness outcomes were
      hospital-acquired MRSA infections and deaths avoided. One-way and two-way
      sensitivity analyses and Monte Carlo simulations were performed. In the base-case
      analysis, the strategy of active surveillance plus decolonization dominated (i.e.
      lower cost and greater effectiveness) both the comparison strategies of active
      surveillance and no surveillance. In addition, the active surveillance strategy
      dominated the strategy of no surveillance. One-way and two-way sensitivity
      analyses demonstrated that at low levels of direct benefit of decolonization (1
      4%), the strategy of active surveillance plus decolonization would no longer be
      dominant. In the probabilistic sensitivity analysis, active surveillance plus
      decolonization dominated both the other two strategies, and the active
      surveillance strategy dominated no surveillance in all of 1000 Monte Carlo
      simulations. These results provide a strong economic argument for adding an MRSA
      decolonization protocol to the current VHA active surveillance strategy.

PMID- 20673266
TI  - Matrix-assisted laser desorption ionization time-of-flight mass spectrometry for
      fast and accurate identification of clinically relevant Aspergillus species.
AB  - New Aspergillus species have recently been described with the use of multilocus
      sequencing in refractory cases of invasive aspergillosis. The classical
      phenotypic identification methods routinely used in clinical laboratories failed
      to identify them adequately. Some of these Aspergillus species have specific
      patterns of susceptibility to antifungal agents, and misidentification may lead
      to inappropriate therapy. We developed a matrix-assisted laser desorption
      ionization time-of-flight (MALDI-TOF) mass spectrometry (MS)-based strategy to
      adequately identify Aspergillus species to the species level. A database
      including the reference spectra of 28 clinically relevant species from seven
      Aspergillus sections (five common and 23 unusual species) was engineered. The
      profiles of young and mature colonies were analysed for each reference strain,
      and species-specific spectral fingerprints were identified. The performance of
      the database was then tested on 124 clinical and 16 environmental isolates
      previously characterized by partial sequencing of the beta-tubulin and calmodulin
      genes. One hundred and thirty-eight isolates of 140 (98.6%) were correctly
      identified. Two atypical isolates could not be identified, but no isolate was
      misidentified (specificity: 100%). The database, including species-specific
      spectral fingerprints of young and mature colonies of the reference strains,
      allowed identification regardless of the maturity of the clinical isolate. These
      results indicate that MALDI-TOF MS is a powerful tool for rapid and accurate
      identification of both common and unusual species of Aspergillus. It can give
      better results than morphological identification in clinical laboratories.

PMID- 20673267
TI  - Perspectives from Spanish infectious diseases professionals on 2009 A (H1N1)
      influenza: the third half.
AB  - The first influenza pandemic in more than 40 years was declared in 2009. We aimed
      to evaluate the beliefs of Spanish infectious diseases professionals regarding
      several aspects of 2009 A (H1N1) influenza once the epidemic waned. An online
      survey was designed and distributed among members of the Spanish Society of
      Infectious Diseases and Clinical Microbiology (SEIMC). The survey considered
      hospital organization and preparedness planning and conduct, as well as the
      opinion of the infectious diseases professionals regarding several key issues.
      Between 7 March and 22 March 2010, 303 responses, corresponding to 12.8% of the
      SEIMC membership, were received. Of the respondents, 48.2% were microbiologists
      and 42.3% were clinicians dealing with infectious diseases. Forty-one per cent of
      respondents did not believe that 2009 A (H1N1) influenza had a more severe
      presentation than other seasonal influenzas. Only 5% fully agreed that 2009 A
      (H1N1) influenza had a more severe presentation. Influenza planning was available
      in 69.7% of represented institutions before the arrival of 2009 A (H1N1)
      influenza, and was considered to be useful, to different extents, by most
      professionals. In most institutions (88.3%), a multidisciplinary team was created
      to coordinate local pandemic influenza actions. The most successful protocols
      were those provided by regional healthcare authorities, followed by those from
      the CDC. The most problematic issues regarding 2009 A (H1N1) influenza were the
      management of patients in the emergency room and the vaccination and awareness of
      healthcare professionals (HCPs) regarding infection control. Microbiological
      diagnosis and the availability of antivirals were the least problematic areas.
      Although the majority of surveyed infectious diseases professionals did not
      believe that 2009 A (H1N1) influenza had an especially severe presentation, most
      of them agreed with the way that this epidemic was managed in their institutions.

PMID- 20673268
TI  - Accidental blood exposures among medical residents in Paris, France.
AB  - Accidental blood exposure (ABE) exposes healthcare workers, including medical
      residents, to the risk of occupational infection. We aimed to determine the
      characteristics of ABEs in residents with an anonymous self-reporting electronic
      questionnaire. A total of 350 residents (33% from surgical disciplines) entered
      this survey. One hundred and eighty-five residents (52%) reported at least one
      ABE during their residency (median, 2; range, 1-25), 53% of which occurred in
      operating theatres. Sixty-nine per cent of residents followed the current
      procedures for local disinfection. ABEs were notified to the hospital
      administration by 62% of residents, but only 51% of residents were referred to
      the occupational medicine department. The most frequently reported concerns
      following ABEs were human immunodeficiency virus (52%) and hepatitis C virus
      infection (39%). In 74% of cases, the serological status of the index patient was
      investigated. Only 54% of residents were aware of their hepatitis B surface
      antibody titres. Medical residents behaved inappropriately in 33% of cases in
      this survey. Further educational programmes should include residents, and not
      only senior healthcare workers, in order to improve individual behaviours.

PMID- 20673269
TI  - Epidemiology of methicillin-susceptible Staphylococcus aureus lineages in five
      major African towns: high prevalence of Panton-Valentine leukocidin genes.
AB  - The epidemiology of methicillin-susceptible Staphylococcus aureus (MSSA) in
      Africa is poorly documented. From January 2007 to March 2008, 555 S. aureus
      isolates were collected from five African towns in Cameroon, Madagascar, Morocco,
      Niger, and Senegal; among these, 456 unique isolates were susceptible to
      methicillin. Approximately 50% of the MSSA isolates from each different
      participating centre were randomly selected for further molecular analysis. Of
      the 228 isolates investigated, 132 (58%) belonged to five major multilocus
      sequence typing (MLST) clonal complexes (CCs) (CC1, CC15, CC30, CC121 and CC152)
      that were not related to any successful methicillin-resistant S. aureus (MRSA)
      clones previously identified in the same study population. The luk-PV genes
      encoding Panton-Valentine leukocidin (PVL), present in 130 isolates overall
      (57%), were highly prevalent in isolates from Cameroon, Niger, and Senegal (West
      and Central Africa). This finding is of major concern, with regard to both a
      source of severe infections and a potential reservoir for PVL genes. This
      overrepresentation of PVL in MSSA could lead to the emergence and spread of
      successful, highly virulent PVL-positive MRSA clones, a phenomenon that has
      already started in Africa.

PMID- 20673270
TI  - Multiclonal epidemic of Klebsiella pneumoniae isolates producing DHA-1 in a
      Spanish hospital.
AB  - Between June 2007 and January 2008, 26 Klebsiella pneumoniae isolates carrying
      bla(DHA-1) on an IncL/M plasmid were obtained from clinical samples at Granollers
      Hospital, Barcelona, Spain. Three of the isolates also carried a bla(CTX-M-15)
      gene. The 26 isolates showed 11 pulsed-field gel electrophoresis (PFGE) patterns.
      Multilocus sequence typing showed that PFGE patterns A, B and C belonged to
      sequence type (ST)17, D to ST13, E to ST427, F and G to ST416, H to ST37, I to
      ST440, J to ST326, and K to ST428. Results demonstrated the effectiveness of the
      infection control programme in place at the centre. This study reports the first
      characterization of STs for bla(DHA-1) -producing K. pneumoniae isolates.

PMID- 20673271
TI  - Serum (1 -> 3)-beta-D-glucan measurement as an early indicator of Pneumocystis
      jirovecii pneumonia and evaluation of its prognostic value.
AB  - Pneumocystis jirovecii (carinii) pneumonia (PJP) is a major cause of disease in
      immunocompromised individuals. However, until recently no reliable and specific
      serological parameters for the diagnosis of PJP have been available. (1 -> 3)
      beta-D-Glucan (BG) is a cell wall component of P. jirovecii and of various other
      fungi. Data from the past few years have pointed to serum measurement of BG as a
      promising new tool for the diagnosis of PJP. We therefore conducted a
      retrospective study on 50 patients with PJP and 50 immunocompromised control
      patients to evaluate the diagnostic performance of serum BG measurement. Our
      results show an excellent diagnostic performance with a sensitivity of 98.0% and
      a specificity of 94%. While the positive predictive value was only 64.7%, the
      negative predictive value was 99.8% and therefore a negative BG result almost
      rules out PJP. BG levels were already strongly elevated in an average of 5 days
      and up to 21 days before microbiological diagnosis demonstrating that the
      diagnosis could have been confirmed earlier. BG levels at diagnosis and maximum
      BG levels during follow-up did not correlate with the outcome of patients or with
      the P. jirovecii burden in the lung as detected by Real-Time PCR. Therefore,
      absolute BG levels seem to be of no prognostic value. Altogether, BG is a
      reliable parameter for the diagnosis of PJP and could be used as a preliminary
      test for patients at risk before a bronchoalveolar lavage is performed.

PMID- 20673272
TI  - Stationary biofilm growth normalizes mutation frequencies and mutant prevention
      concentrations in Pseudomonas aeruginosa from cystic fibrosis patients.
AB  - Bacterial biofilms play an important role in the persistent colonization of the
      respiratory tract in cystic fibrosis (CF) patients. The trade-offs among
      planktonic or sessile modes of growth, mutation frequency, antibiotic
      susceptibility and mutant prevention concentrations (MPCs) were studied in a well
      defined collection of 42 CF Pseudomonas aeruginosa isolates. MICs of
      ciprofloxacin, tobramycin, imipenem and ceftazidime increased in the biofilm mode
      of growth, but not the MPCs of the same drugs. The mutation frequency median was
      significantly higher in planktonic conditions (1.1 * 10(-8)) than in biofilm (9.9
      * 10(-9)) (p 0.015). Isolates categorized as hypomutable increased their mutation
      frequency from 3.6 * 10(-9) in the planktonic mode to 6 * 10(-8) in biofilm,
      whereas normomutators (from 9.4 * 10(-8) to 5.3 * 10(-8)) and hypermutators (from
      1.6 * 10(-6) to 7.7 * 10(-7)) decreased their mutation frequencies in biofilm.
      High and low mutation frequencies in planktonic growth converge into the
      normomutable category in the biofilm mode of growth of CF P. aeruginosa, leading
      to stabilization of MPCs. This result suggests that once the biofilm mode of
      growth has been established, the propensity of CF P. aeruginosa populations to
      evolve towards resistance is not necessarily increased.

PMID- 20673273
TI  - Thoracoscopic lung biopsies in heaves-affected horses using a bipolar tissue
      sealing system.
AB  - OBJECTIVE: To validate the use of the LigaSureTM Vessel Sealing System (LVSS) to
      perform thoracoscopic lung tissue biopsies in heaves-affected horses. STUDY
      DESIGN: Prospective clinical study. ANIMALS: Heaves-affected horses (n=12).
      METHODS: Lung biopsies (n=34) were collected with the LVSS (2-4 biopsies/horse)
      in horses with and without clinical signs of heaves. Thoracoscope (13th
      intercostal space [ICS]) and 2 instruments (between the 12-15th ICS) portals were
      used. Selected clinical and arterial blood gas variables were monitored.
      Postoperative pneumothorax was evaluated. Depth of thermal injury to the
      surrounding tissue and representativeness of the biopsies were determined.
      RESULTS: Mean surgical time was 22.9+/-8.0 minutes. The complication rate was
      5.6%, and primarily related to a focal inadequate sealing of the biopsy margin.
      Five horses in exacerbation required intraoperative intranasal O(2) . Mean PaO(2)
      was significantly lower in heaves-affected horses with clinical signs compared
      with those without clinical signs. Postoperative pneumothorax was detected
      radiographically after 20 of the 34 procedures. One horse with clinical signs of
      heaves developed a fatal tension pneumothorax 5 days postoperatively despite
      close radiographic monitoring. CONCLUSION: Thoracoscopic lung biopsy using LVSS
      is a rapid and effective technique to harvest peripheral lung tissues from heaves
      affected horses. Although the complication rate was tolerable, tension
      pneumothorax was a potential life-threatening complication because of incomplete
      lung sealing. CLINICAL RELEVANCE: LVSS can be used with relative safety to
      perform thoracoscopic lung biopsy, but close postoperative monitoring is
      necessary to avoid tension pneumothorax.

PMID- 20673274
TI  - Comparison of 5 surgical techniques for partial liver lobectomy in the dog for
      intraoperative blood loss and surgical time.
AB  - OBJECTIVE: To compare surgical time and intraoperative blood loss for 5 partial
      liver lobectomy techniques in the dog. STUDY DESIGN: Experimental in vivo study.
      ANIMALS: Dogs (n=10). METHODS: Five surgical techniques (SurgiTie(TM) ;
      LigaSure(TM) ; Ultracision((r)) Harmonic Scalpel [UAS]; Suction+Clip;
      Suction+thoracoabdominal stapler [TA]) for partial liver lobectomy in dogs were
      evaluated and compared for total surgical time and intraoperative blood loss.
      Body weight, activated clotting time (ACT), heart rate, and intraoperative blood
      pressure (BP) were recorded. Blood loss was determined by adding the weight of
      the blood soaked sponges during surgery (1 g=1 mL) to the amount of suctioned
      blood (mL). Surgical time (in seconds) was determined from the start of the
      lobectomy until cessation of bleeding from the stump. Mean surgical time and mean
      blood loss for each technique were compared using a Tukey's multiple comparison
      test. RESULTS: No significant differences were found between dogs for weight,
      ACT, heart rate, and intraoperative BP. No complications were seen with the
      SurgiTie(TM) technique in 9 of 10 cases. There was no significant difference in
      surgical time between techniques however there was a significant difference for
      blood loss; the Suction+Clip method had significantly more blood loss than the
      other techniques. CONCLUSIONS: Skeletonization of the lobar vessels before
      individually clipping them (Suction+Clip) resulted in a higher blood loss than
      using Suction+TA, UAS, SurgiTie(TM) or the LigaSure(TM) device. The SurgiTie(TM)
      appears to be an acceptable method for partial liver lobectomy. CLINICAL
      RELEVANCE: Although skeletonization and individually clipping the vessels had the
      highest blood loss, it still was <7.5% of total blood volume. All 5 techniques
      should be safe for clinical use in small to medium sized dogs up to 26 kg.

PMID- 20673275
TI  - Standing lateral thoracotomy in horses: indications, complications, and outcomes.
AB  - OBJECTIVE: To describe the indications for, complications arising from, and
      outcome of horses that had standing lateral thoracotomy for pleural or
      pericardial disease. STUDY DESIGN: Case series. ANIMALS: Horses (n=16). METHODS:
      Medical records (January 1990-December 2008) of sedated standing horses that had
      lateral thoracotomy were reviewed. Clinical and surgical findings, perioperative
      and short-term complications were recorded. Long-term (>6 months) outcome was
      determined through telephone conversations with owners and veterinarians.
      RESULTS: Mean (+/-SD) horse age was 6.6+/-5.3 years (range, 1-15 years).
      Thoracotomy was most commonly for treatment of recurrent or chronic pleural
      infection (94%). Anaerobic bacteria were frequently isolated from pleural
      effusion associated with pleuropneumonia (63%). Right lateral intercostal
      thoracotomy was performed in 13 horses (82%); intercostal muscle myectomy in 5
      horses; and rib resection in 1. Perioperative complications were hemipneumothorax
      (2 horses) and short-term complications included cellulitis and abscessation of
      the thoracotomy site (6 horses). Fourteen (88%) horses survived to discharge and
      46% of horses that survived returned to their previous level of athletic
      activity. CONCLUSIONS: Lateral thoracotomy is well tolerated by standing sedated
      horses with minimal perioperative and short-term complications. CLINICAL
      RELEVANCE: Standing lateral thoracotomy should be considered for the treatment of
      complicated pleuropneumonia in horses.

PMID- 20673277
TI  - TRP-ing off the p53 apoptotic switch.

PMID- 20673276
TI  - Evaluation of a midhumeral block of the radial, ulnar, musculocutaneous and
      median (RUMM block) nerves for analgesia of the distal aspect of the thoracic
      limb in dogs.
AB  - OBJECTIVE: To evaluate a technique for midhumeral peripheral nerve blockade in
      the dog. STUDY DESIGN: Cadaveric technique development; in vivo placebo
      controlled, prospective crossover study. ANIMALS: Canine cadavers (n=38) and 8
      clinically healthy, adult hound dogs. METHODS: A technique for peripheral block
      of the radial, ulnar, musculocutaneous, and median nerves (RUMM block) was
      evaluated using cadaver limbs. Eight purpose-bred, research dogs were
      anesthetized; a RUMM block was performed on each thoracic limb. One limb from
      each dog randomly received 0.5% bupivacaine and the opposite limb was assigned to
      receive sterile saline solution as a control. After recovery from anesthesia,
      skin sensation at selected dermatomes was evaluated for 24 hours using a
      mechanical stimulus. Weight-bearing, conscious proprioception, and withdrawal
      reflex were also evaluated. One month after initial testing, each dog was
      reanesthetized and each limb received the opposite treatment. RESULTS: Sensory
      thresholds were significantly increased over baseline measurements when compared
      with control limbs for all nerves. Complete sensory block was achieved in radial
      (15/16), ulnar (3/16), musculocutaneous (8/16), and median (11/16) nerves, using
      a mechanical stimulus of analgesia. Complete simultaneous block of all nerves was
      only obtained in 1 of 16 limbs. CONCLUSION: RUMM block resulted in
      desensitization of the skin in the associated dermatomes for 4-10 hours. Complete
      sensory block of the dermatomes supplied by the radial nerve was most consistent.
      CLINICAL RELEVANCE: RUMM block may be an effective technique to provide
      adjunctive analgesia for dogs undergoing surgery of the distal aspect of the
      thoracic limb.

PMID- 20673278
TI  - Prevalence of obesity in Switzerland 1992-2007: the impact of education, income
      and occupational class.
AB  - Prevalence of excess weight varies substantially by socioeconomic position (SEP).
      SEP can be defined with different indicators. The strength of the association of
      SEP with excess weight differs by SEP indicator, between populations and over
      time. We examined the prevalence of overweight and obesity (body mass index 25
      29.9 and >=30 kg m(-2) ) in Switzerland by educational level, household income
      tertile and occupational class (three categories for each indicator). Self
      reported data stem from four cross-sectional population surveys including 53 588
      persons aged between 25 and 74 years. The overall prevalence of overweight
      increased between 1992 and 2007 from 37.4% to 41.4% in men and from 18.8% to
      21.9% in women. Obesity prevalence increased from 7.2% to 9.7% in men and from
      5.4% to 8.6% in women. Inequalities were calculated with multivariable logistic
      regression. Inequalities were larger in women than in men and for obesity than
      for overweight. However, overweight and obesity inequalities did not
      significantly change over time, despite overall increasing prevalence. Although
      all SEP indicators were independently associated with excess weight, the
      association was strongest with education, particularly in women. Programmes and
      policies aimed at preventing excess weight should target individuals with low
      education early in life.

PMID- 20673280
TI  - A systematic review of primary healthcare provider education and training using
      the Chronic Care Model for childhood obesity.
AB  - The purpose of this systematic review was to examine 15 studies which evaluated
      interventions aimed at improving primary care providers' identification,
      assessment, prevention and/or management of obesity in children and adolescents.
      Interventions were evaluated in terms of length, components addressing nutrition,
      physical activity and behavioural counselling consistent with expert
      recommendations, and inclusion of components of the Chronic Care Model. Overall,
      training interventions were delivered face to face or in a combination of
      lecture, assigned readings, preceptorship with experienced providers, and
      critiqued evaluations of interactions of the provider with the patient and
      family. Many studies incorporated training of providers as an initial step prior
      to delivering an obesity intervention for children and adolescents measuring
      weight loss and behaviour change as outcomes. Each study was evaluated for
      components of the Chronic Care Model. The interventions most frequently utilized
      the elements of self-management support (69%), decision support (100%), delivery
      system support (77%) and clinical information systems (23%). Although science in
      this area is emerging, results suggest that intervention programmes that included
      more components of the Chronic Care Model were more effective.

PMID- 20673281
TI  - Xylem function and growth rate interact to determine recovery rates after
      exposure to extreme water deficit.
AB  - * Motivated by the urgent need to understand how water stress-induced embolism
      limits the survival and recovery of plants during drought, the linkage between
      water-stress tolerance and xylem cavitation resistance was examined in one of the
      world's most drought resistant conifer genera, Callitris. * Four species were
      subjected to drought treatments of -5, -8 and -10 MPa for a period of 3-4 wk,
      after which plants were rewatered. Transpiration, basal growth and leaf water
      potential were monitored during and after drought. * Lethal water potential was
      correlated with the tension producing a 50% loss of stem hydraulic conductivity.
      The most resilient species suffered minimal embolism and recovered gas exchange
      within days of rewatering from -10 MPa, while the most sensitive species suffered
      major embolism and recovered very slowly. The rate of repair of water transport
      in the latter case was equal to the rate of basal area growth, indicating xylem
      reiteration as the primary means of hydraulic repair. * The survival of, and
      recovery from, water stress in Callitris are accurately predicted by the
      physiology of the stem water-transport system. As the only apparent means of
      xylem repair after embolism, basal area growth is a critical part of this
      equation.

PMID- 20673279
TI  - Migraine and obesity: epidemiology, possible mechanisms and the potential role of
      weight loss treatment.
AB  - Migraine and obesity are two public health problems of enormous scope that are
      responsible for significant quality of life impairment and financial cost. Recent
      research suggests that these disorders may be directly related with obesity
      exacerbating migraine in the form of greater headache frequency and severity, or
      possibly increasing the risk for having migraine. The relationship between
      migraine and obesity may be explained through a variety of physiological,
      psychological and behavioural mechanisms, many of which are affected by weight
      loss. Given that weight loss might be a viable approach for alleviating migraine
      in obese individuals, randomized controlled trials are needed to test the effect
      of weight loss interventions in obese migraineurs. Large-scale weight loss trials
      have shown that behavioural interventions, in particular, can produce sustained
      weight losses and related cardiovascular improvements in patients who are diverse
      in body weight, age and ethnicity. Consequently, these interventions may provide
      a useful treatment model for showing whether weight loss reduces headache
      frequency and severity in obese migraineurs, and offering further insight into
      pathways through which weight loss might exert an effect.

PMID- 20673282
TI  - The use of FLP-mediated recombination for the functional analysis of an effector
      gene family in the biotrophic smut fungus Ustilago maydis.
AB  - *In the Ustilago maydis genome, several novel secreted effector proteins are
      encoded by gene families. Because of the limited number of selectable markers,
      the ability to carry out sequential gene deletions has limited the analysis of
      effector gene families that may have redundant functions. *Here, we established
      an inducible FLP-mediated recombination system in U. maydis that allows repeated
      rounds of gene deletion using a single selectable marker (Hyg(R)). To avoid
      genome rearrangements via FRT sites remaining in the genome after excision,
      different mutated FRT sites were introduced. *The FLP-mediated selectable marker
      removal technique was successfully applied to delete a family of 11 effector
      genes (eff1) using five sequential rounds of recombination. We showed that
      expression of all 11 genes is up-regulated during the biotrophic phase. Strains
      carrying deletions of 9 or all 11 genes showed a significant reduction in
      virulence, and this phenotype could be partially complemented by the introduction
      of different members from the gene family, demonstrating redundancy. *The
      establishment of the FLP/FRT system in a plant pathogenic fungus paves the way
      for analyzing multigene families with redundant functions.

PMID- 20673283
TI  - Seed dispersal effectiveness revisited: a conceptual review.
AB  - Growth in seed dispersal studies has been fast-paced since the seed disperser
      effectiveness (SDE) framework was developed 17 yr ago. Thus, the time is ripe to
      revisit the framework in light of accumulated new insight. Here, we first present
      an overview of the framework, how it has been applied, and what we know and do
      not know. We then introduce the SDE landscape as the two-dimensional
      representation of the possible combinations of the quantity and the quality of
      dispersal and with elevational contours representing isoclines of SDE. We discuss
      the structure of disperser assemblages on such landscapes. Following this we
      discuss recent advances and ideas in seed dispersal in the context of their
      impacts on SDE. Finally, we highlight a number of emerging issues that provide
      insight into SDE. Overall, the SDE framework successfully captures the
      complexities of seed dispersal. We advocate an expanded use of the term dispersal
      encompassing the multiple recruitment stages from fruit to adult. While this
      entails difficulties in estimating SDE, it is a necessary expansion if we are to
      understand the central relevance of seed dispersal in plant ecology and
      evolution.

PMID- 20673284
TI  - Is tree root respiration more sensitive than heterotrophic respiration to changes
      in soil temperature?

PMID- 20673285
TI  - Environmental change without climate change?

PMID- 20673286
TI  - Ectomycorrhizal fungi and interspecific competition: species interactions,
      community structure, coexistence mechanisms, and future research directions.
AB  - The field of ectomycorrhizal fungal (EMF) ecology has largely developed outside
      the ecological mainstream, owing in large part to the challenges in studying the
      structure and dynamics of EMF communities. With advances in molecular
      identification and other research techniques, however, there has been growing
      interest among mycologists and ecologists in understanding how different
      ecological factors affect EMF community structure and diversity. While factors
      such as soil chemistry and host specificity have long been considered important,
      an increasing number of laboratory and field studies have documented that
      interspecific competition also has a major impact on EMF species interactions and
      may significantly influence EMF community structure. In this review, I examine
      the progress that has been made in understanding the nature of EMF competition.
      Currently, there are four conclusions that can be drawn: negative competitive
      effects are rarely reciprocal; competitive outcomes are environmentally context
      dependent; field distributions often reflect competitive interactions; and timing
      of colonization influences competitive success. In addition, I highlight recent
      studies documenting links between competitive coexistence and EMF community
      structure, including checkerboard distributions, lottery models, storage effects,
      and colonization-competition tradeoffs. Finally, I discuss several aspects of EMF
      competition needing further investigation and some newer methods with which to
      address them.

PMID- 20673287
TI  - Molecular traits controlling host range and adaptation to plants in Ralstonia
      solanacearum.
AB  - Ralstonia solanacearum is regarded as one of the world's most important bacterial
      plant pathogens because of its aggressiveness, large host range, broad
      geographical distribution and long persistence in soil and water environments.
      This root pathogen is an attractive model to investigate the question of host
      adaptation as it exhibits a remarkably broad host range, being able to infect
      numerous plant species belonging to different botanical families. Several
      effector proteins transiting through the type III secretion system have been
      shown to restrict or extend specifically the host range of the bacterium. Recent
      investigations on the mechanisms that coordinate changes in gene expression
      during the passage between saprophytism and life within host tissues have allowed
      the identification of other molecular determinants implicated in the adaptation
      of R. solanacearum to its hosts and pathogenesis. Among these determinants are
      genes involved in chemotaxis, secondary metabolic pathways and the detoxification
      of various antimicrobial compounds, and genes directing the biosynthesis of
      phytohormones or adherence factors. The regulation of many of these genes is
      coordinated by the master pathogenicity regulator HrpG. These hrpG-dependent
      genes control major steps during the interaction with plant cells, and probably
      determine the ecological behaviour of the microorganism, being required for the
      establishment of pathogenesis or mutualism.

PMID- 20673288
TI  - Multilocus analysis of genetic divergence between outcrossing Arabidopsis
      species: evidence of genome-wide admixture.
AB  - * Outcrossing Arabidopsis species that diverged from their inbreeding relative
      Arabidopsis thaliana 5 million yr ago and display a biogeographical pattern of
      interspecific sympatry vs intraspecific allopatry provides an ideal model for
      studying impacts of gene introgression and polyploidization on species
      diversification. * Flow cytometry analyses detected ploidy polymorphisms of 2*
      and 4* in Arabidopsis lyrata ssp. kamchatica of Taiwan. Genomic divergence
      between species/subspecies was estimated based on 98 randomly chosen nuclear
      genes. Multilocus analyses revealed a mosaic genome in diploid A. l. kamchatica
      composed of Arabidopsis halleri-like and A. lyrata-like alleles. * Coalescent
      analyses suggest that the segregation of ancestral polymorphisms alone cannot
      explain the high inconsistency between gene trees across loci, and that gene
      introgression via diploid A. l. kamchatica likely distorts the molecular
      phylogenies of Arabidopsis species. However, not all genes migrated across
      species freely. Gene ontology analyses suggested that some nonmigrating genes
      were constrained by natural selection. * High levels of estimated ancestral
      polymorphisms between A. halleri and A. lyrata suggest that gene flow between
      these species has not completely ceased since their initial isolation.
      Polymorphism data of extant populations also imply recent gene flow between the
      species. Our study reveals that interspecific gene flow affects the genome
      evolution in Arabidopsis.

PMID- 20673289
TI  - Sleep onset and cardiovascular activity in primary insomnia.
AB  - The transition from wakefulness to sleep is characterized typically by a shift
      from sympathetic to parasympathetic regulation. Physiological functions,
      depending on the neurovegetative system, decrease overall. Previous studies have
      shown cardiovascular and electroencephalographic hyperactivity during wakefulness
      and sleep in insomniacs compared with normal sleepers, but there is very little
      evidence of this in the process of sleep onset. The purpose of this study was to
      compare cardiovascular and autonomic responses before and after falling asleep in
      eight insomniacs (who met DSM-IV criteria for primary insomnia) and eight normal
      sleepers. Non-invasive measures of heart rate (HR), stroke volume (SV), cardiac
      output (CO) and pre-ejection period (PEP) were collected by impedance
      cardiography during a night of polysomnographic recording. Frequency domain
      measures [low-frequency (LF), high-frequency (HF)] of heart rate variability
      (HRV) were also estimated. Decrements in HR and CO and increases in SV and HF
      normalized units (n.u.) were found in both groups after sleep onset compared with
      wakefulness. Conversely, PEP (related inversely to sympathetic beta-adrenergic
      activity) showed increases after sleep onset in controls, but remained unchanged
      in insomniacs. PEP was also significantly lower in insomniacs than in normal
      sleepers in both conditions. These data suggest that, whereas normal sleepers
      follow the expected progressive autonomic drop, constant sympathetic
      hyperactivation is detected in insomniacs. These results support the aetiological
      hypothesis of physiological hyperarousal underlying primary insomnia.

PMID- 20673290
TI  - Effects of vigorous late-night exercise on sleep quality and cardiac autonomic
      activity.
AB  - Sleep is the most important period for recovery from daily load. Regular physical
      activity enhances overall sleep quality, but the effects of acute exercise on
      sleep are not well defined. In sleep hygiene recommendations, intensive
      exercising is not suggested within the last 3 h before bed time, but this
      recommendation has not been adequately tested experimentally. Therefore, the
      effects of vigorous late-night exercise on sleep were examined by measuring
      polysomnographic, actigraphic and subjective sleep quality, as well as cardiac
      autonomic activity. Eleven (seven men, four women) physically fit young adults
      (VO(2max) 54+/-8 mL.kg(-1).min(-1) , age 26+/-3 years) were monitored in a sleep
      laboratory twice in a counterbalanced order: (1) after vigorous late-night
      exercise; and (2) after a control day without exercise. The incremental cycle
      ergometer exercise until voluntary exhaustion started at 21:00+/-00:28 hours,
      lasted for 35+/-3 min, and ended 2:13+/-00:19 hours before bed time. The
      proportion of non-rapid eye movement sleep was greater after the exercise day
      than the control day (P<0.01), while no differences were seen in actigraphic or
      subjective sleep quality. During the whole sleep, no differences were found in
      heart rate (HR) variability, whereas HR was higher after the exercise day than
      the control day (54+/-7 versus 51+/-7, P<0.01), and especially during the first
      three sleeping hours. The results indicate that vigorous late-night exercise does
      not disturb sleep quality. However, it may have effects on cardiac autonomic
      control of heart during the first sleeping hours.

PMID- 20673291
TI  - Sleep-related memory consolidation in primary insomnia.
AB  - It has been suggested that healthy sleep facilitates the consolidation of newly
      acquired memories and underlying brain plasticity. The authors tested the
      hypothesis that patients with primary insomnia (PI) would show deficits in sleep
      related memory consolidation compared to good sleeper controls (GSC). The study
      used a four-group parallel design (n=86) to investigate the effects of 12 h of
      night-time, including polysomnographically monitored sleep ('sleep condition' in
      PI and GSC), versus 12 h of daytime wakefulness ('wake condition' in PI and GSC)
      on procedural (mirror tracing task) and declarative memory consolidation (visual
      and verbal learning task). Demographic characteristics and memory encoding did
      not differ between the groups at baseline. Polysomnography revealed a
      significantly disturbed sleep profile in PI compared to GSC in the sleep
      condition. Night-time periods including sleep in GSC were associated with (i) a
      significantly enhanced procedural and declarative verbal memory consolidation
      compared to equal periods of daytime wakefulness in GSC and (ii) a significantly
      enhanced procedural memory consolidation compared to equal periods of daytime
      wakefulness and night-time sleep in PI. Across retention intervals of daytime
      wakefulness, no differences between the experimental groups were observed. This
      pattern of results suggests that healthy sleep fosters the consolidation of new
      memories, and that this process is impaired for procedural memories in patients
      with PI. Future work is needed to investigate the impact of treatment on
      improving sleep and memory.

PMID- 20673292
TI  - Nasal pillows as an alternative interface in patients with obstructive sleep
      apnoea syndrome initiating continuous positive airway pressure therapy.
AB  - Side-effects directly due to the nasal mask are common in patients with
      obstructive sleep apnoea syndrome (OSAS) commencing continuous positive airway
      pressure (CPAP). Recently, nasal pillows have been designed to overcome these
      issues. Limited evidence exists of the benefits and effectiveness of these
      devices. Twenty-one patients (19 male, 49+/-10years) with the established
      diagnosis of OSAS [apnoea/hypopnoea index (AHI): 52+/-22] and who had a
      successful CPAP titration were commenced on CPAP therapy (10+/-2cmH2O), and
      randomized to 4weeks of a nasal pillow (P) and a standard nasal mask (M) in a
      crossover design. Outcome measures were objective compliance, AHI, quality of
      life, Epworth Sleepiness Score (ESS) and CPAP side-effects. There was no
      difference in compliance (M versus P: 5.1+/-1.9h versus 5.0+/-1.7h; P=0.701) and
      AHI (2.6+/-2.7 versus 3.0+/-2.9; P=0.509). Quality of life and ESS improved with
      CPAP, but there was no difference in the extent of improvement between both
      devices. Usage of nasal pillows resulted in less reported pressure on the face
      and more subjects found the nasal pillow the more comfortable device. However,
      there was no clear overall preference for either device at the end of the study
      (mask=57%, pillow=43%; P=0.513). The applied CPAP pressure did not correlate with
      compliance, AHI and ESS. Furthermore, no differences in outcome parameters were
      noted comparing groups with CPAP pressure <10 and >=10cm H(2) O. Nasal pillows
      are equally effective in CPAP therapy, but do not generally lead to improved
      compliance.

PMID- 20673293
TI  - Beneficial effects of omega-3 fatty acids in cardiovascular disease.
AB  - There is a large body of evidence supporting beneficial effects of omega-3 fatty
      acids for both primary and secondary prevention of cardiac disease in people.
      However, evidence is increasing for the use of omega-3 fatty acids in dogs with
      cardiac disease as well. Omega-3 fatty acids' anti-inflammatory and anti
      arrhythmic effects may be beneficial in managing the loss of lean body mass and
      arrhythmias that are common in heart failure. However, omega-3 fatty acids also
      may have positive effects on myocardial energy metabolism, endothelial function,
      heart rate and blood pressure, and immune function. Additional research is needed
      to determine optimal indications, doses and formulations for dogs and cats with
      cardiac disease.

PMID- 20673294
TI  - A structural equation model relating objective and subjective masticatory
      function and oral health-related quality of life in patients with removable
      partial dentures.
AB  - The aim of this study was to investigate the relationships between objective
      masticatory function with respect to masticatory performance and food mixing
      ability, patients' perception of chewing ability and oral health-related quality
      of life (OHRQoL). Partially dentate patients with removable partial dentures (n =
      131, mean age 67.1 year) participated in the study. Four tests were performed to
      evaluate objective and subjective masticatory function and OHRQoL. Masticatory
      performance and food mixing ability were assessed using peanuts or a two-coloured
      wax cube as test items. Patients' perception of chewing ability was rated using a
      food intake questionnaire. OHRQoL was measured using the Japanese version of the
      oral health impact profile. A structural equation model was constructed based on
      hypothesis in which objective masticatory function would be related to OHRQoL via
      perceived chewing ability as a mediator. Structural equation modelling analysis
      found a statistically significant medium effect of perceived chewing ability on
      OHRQoL and statistically significant medium or small effects of masticatory
      performance on perceived chewing ability and OHRQoL (P < 0.05); however, the
      effect of food mixing ability on perceived chewing ability or OHRQoL was not
      statistically significant (P > 0.05). A fit index indicated that the model fitted
      well to the data (Goodness-of-fit index = 0.99). These results suggest that
      perceived chewing ability is a critical factor for OHRQoL and that masticatory
      performance rather than food mixing ability is important for perceived chewing
      ability and OHRQoL in patients with removable partial dentures.

PMID- 20673295
TI  - Material degradation in implant-retained cobalt-chrome and titanium frameworks.
AB  - The purpose of the study was to estimate in vitro material degradation in
      implants and cobalt-chrome or titanium frameworks, before and after exposure to
      artificial saliva. Four full-arch implant frameworks were fabricated according to
      the CrescoTM method (Astra Tech AB, Molndal, Sweden), two in a cobalt-chrome
      alloy and two in commercially pure (CP) titanium. They were cut vertically, and
      the three central sections of each framework were used. Element leakage into an
      artificial saliva solution was observed with mass spectrometry. Before artificial
      saliva exposure, three Branemark System((r)) implants (Nobel Biocare AB,
      Gothenburg, Sweden) were screw-retained to cobalt-chrome sections, and three to
      titanium sections. The contact surfaces with the implants of the framework
      sections and the corresponding surfaces of six implants were examined with
      optical interferometry before and after exposure to artificial saliva to evaluate
      material degradation. Conventional descriptive statistics were used to present
      the mass spectrometry and interferometry data. One-way anova and Dunnett's T3
      post hoc test were used to identify and study differences between the groups. To
      highlight changes within the groups, the Student's t-test was used. The
      significance level was set at 5%. There was significantly more leakage of cobalt
      elements than of titanium and chrome (P < 0.05). After saliva exposure and
      framework connection, the implants roughened (P < 0.05). The titanium frameworks
      were generally rougher than the cobalt-chrome frameworks, both before and after
      saliva exposure (P < 0.05). The findings in this study suggest active material
      degradation processes for both implants and framework materials.

PMID- 20673296
TI  - The influence of partial implant-supported restorations on chewing side
      preference.
AB  - This study aimed at determining whether the individual's chewing side preference
      is affected by local effects, produced by the presence of implant-supported
      restorations. The test group included 81 patients with partial implant-supported
      prosthesis. The control group included 108 subjects with no implants. All
      subjects went through a series of laterality tests for chewing and tasks (hand,
      foot, eye and ear) side preference. The preferred chewing side (PCS) was
      determined by observing the first stroke of the chewing cycle during chewing a
      gum. A positive and significant correlation between the chewing side preference
      and the subject's sidedness during the different tasks was examined, by
      performing four Phi correlation tests for: chewing and handedness(r = 0.54; P <
      0.001); chewing and footedness (r = 0.49; P < 0.001); chewing and eyedness (r =
      0.65; P < 0.001) and chewing and earedness (r = 0.66, P < 0.001). Of the
      subjects, 78.3% preferred the right side for chewing, 19.1% preferred the left
      and 2.1% had no clear side preference. There was no statistical difference in
      chewing side preference distribution between genders. The distribution of chewing
      side preference was not significantly affected by the location of missing teeth
      or implants. In conclusion, implant placement will not affect PCS. Therefore,
      information on chewing side preference should be part of the routine preoperative
      examination for implant-supported restorations to provide a better treatment plan
      in those cases that the implant-supported restoration will be on the PCS.

PMID- 20673297
TI  - Manifestation of preferred chewing side for hard food on TMJ disc displacement
      side.
AB  - The purpose of this study was to reveal the relationship between chewing-side
      preference and anterior disc displacement (ADD) of the TMJ. Thirty-two healthy
      subjects with ages ranging from 26 to 34 years were selected from volunteer
      students at the Okayama University Dental School. Subjects were asked to chew
      freely with two kinds of test foods, beef jerky (hard food) and chiffon cake
      (soft food), thus expecting different amounts of mechanical loading on the TMJ.
      One, 4, and 7 s after starting the mastication, subjects were asked to open their
      mouth momentarily to have a digital image of their mouth taken. The bolus
      placement area was measured by processing the digital images, calculated as the
      number of pixel of bolus area. Area asymmetry index was used for the
      determination of preferred chewing side (PCS). Oblique sagittal MRI scanning in
      the closed mouth position was taken to evaluate the articular disc position. In
      asymptomatic subjects with ADD, a significant predominance of the PCS on the
      ipsilateral side of ADD was observed during the mastication of hard food. On the
      contrary, no correlation was found between unilateral ADD and PCS for the soft
      food. From the results of this study, it is suggested that ADD is the associating
      factor of PCS for hard food. Therefore, it would be necessary to break down the
      concept of PCS into at least two categories, one for hard food and one for soft
      food, considering the mechanical loading on the TMJ.

PMID- 20673298
TI  - Muscle moment arms and function of the siamang forelimb during brachiation.
AB  - Moment arms have an important modulating impact on muscle function, as they
      represent the capacity of the muscle to convert muscle action into limb
      movements. In the current paper, we provide muscle moment arm data of the
      forelimb of four siamangs, collected by detailed dissections on unfixed cadavers.
      The aim of this study is to assess the role of different forelimb muscles during
      brachiation. Moment arm data are compared with similar published data of non
      brachiating primates such as macaques, chimpanzees and humans. Our data show that
      shoulder adductors and endorotators and the elbow flexors are built for force
      generation, whereas the shoulder abductors, flexors and exorotators are best
      suited to gain speed and to change direction. Compared to non-brachiating
      species, both elbow and wrist flexors are particularly noticeable in terms of
      moment of force-generating capacity. However, the moment of force-generating
      capacity of the elbow extensor is not negligible, which indicates that the
      triceps also plays an active role, especially at the end of the support phase.
      Except for the elbow flexors, all muscles reach their maximum moment of force
      generating capacity during the support phase of brachiation. When brachiating on
      a more complex setup, the siamang will flex the elbows to angles that induce
      maximum moment arms as well.

PMID- 20673299
TI  - Investigating and modelling pituitary endocrine network function.
AB  - Endocrine cells in the mammalian pituitary are arranged into three-dimensional
      homotypic networks that wire the gland and act to optimise hormone output by
      allowing the transmission of information between cell ensembles in a temporally
      precise manner. Despite this, the structure-function relationships that allow
      cells belonging to these networks to display coordinated activity remain
      relatively uncharacterised. This review discusses the recent technological
      advances that have allowed endocrine cell network structure and function to be
      probed and the mathematical models that can be used to analyse and present the
      resulting data. In particular, we focus on the mechanisms that allow endocrine
      cells to dynamically function as a population to drive hormone release as well as
      the experimental and theoretical methods that are used to track and model
      information flow through the network.

PMID- 20673302
TI  - Mapping of kisspeptin fibres in the brain of the pro-oestrous rat.
AB  - Kisspeptins are a family of small peptides that play a key role in the
      neuroendocrine regulation of the reproductive function through neural pathways
      that have not yet been completely identified. The present study aimed to
      investigate the distribution of kisspeptin neurone fibres in the female rat brain
      by comparing precisely the immunoreactive pattern obtained with two antibodies:
      one specifically directed against kisspeptin-52 (Kp-52), the longest isoform, and
      the other directed against kisspeptin-10 (Kp-10), whose sequence is common to all
      putative mature isoforms. With both antibodies, immunoreactive cell bodies were
      exclusively observed in the arcuate nucleus, and immunoreactive fibres were
      confined to the septo-preoptico-hypothalamic continuum of the brain. Fibres were
      observed in the preoptic area, the diagonal band of Broca, the septohypothalamic
      area, the anteroventral periventricular, suprachiasmatic, supraoptic,
      paraventricular and periventricular nuclei, the dorsal border of the ventromedian
      nucleus, the dorsomedial and arcuate nuclei, and the median eminence. In the
      latter structure, varicose fibres were mainly distributed in the internal layer
      and were detected to a lesser extent throughout the external layer, including
      around the deeper part of the infundibular recess. Most regions of immunoreactive
      cells and fibres matched perfectly for the two antibodies. However, fibres in the
      dorsolateral septum, anterior fornix, accumbens nucleus and the lateral bed
      nucleus of the stria terminalis were only recognised by antibody anti-Kp-10,
      suggesting that anti-Kp-10 may recognise a wider range of kisspeptin isoforms
      than anti-Kp-52 or cross-react with molecules other than kisspeptin in rat
      tissue. Overall, these results illustrate the variety of projection sites of
      kisspeptin neurones in the rat and suggest that these peptides play a role in
      different functions.

PMID- 20673300
TI  - Noradrenergic nuclei that receive sensory input during mating and project to the
      ventromedial hypothalamus play a role in mating-induced pseudopregnancy in the
      female rat.
AB  - In female rats, vaginal-cervical stimulation (VCS) received during mating induces
      bicircadian prolactin surges that are required for the maintenance of pregnancy
      or pseudopregnancy (PSP). The neural circuits that transmit VCS inputs to the
      brain have not been fully described, although mating stimulation is known to
      activate medullary noradrenergic cell groups that project to the forebrain. In
      response to VCS, these neurones release noradrenaline within the ventrolateral
      division of the ventromedial hypothalamus (VMHvl) and the posterodorsal medial
      amygdala (MePD), two forebrain sites that are implicated in the initiation of
      PSP. Noradrenaline receptor activation within the VMHvl is both necessary and
      sufficient for PSP induction, suggesting that noradrenaline acting within the
      VMHvl is particularly important in mediating the effects of VCS towards the
      establishment of PSP. We therefore investigated whether or not endogenous, VCS
      induced noradrenaline release within the VMHvl is involved in PSP induction in
      the rat. Before the receipt of sufficient mating stimulation to induce PSP, a
      retrograde neurotoxin, dopamine-beta-hydroxylase-saporin (DBH-SAP), was infused
      bilaterally into the either the VMHvl or the MePD to selectively destroy afferent
      noradrenergic nuclei in the brainstem. DBH-SAP infusions into the VMHvl lesioned
      mating-responsive noradrenergic neurones in A1 and A2 medullary nuclei and
      reduced the incidence of PSP by 50%. Infusions of DBH-SAP into the MePD had no
      effect on the subsequent induction of PSP. These results suggest that VCS is
      conveyed to mating-responsive forebrain areas by brainstem noradrenergic
      neurones, and that the activity of noradrenergic cells projecting to the VMHvl is
      involved in the induction of PSP.

PMID- 20673303
TI  - Treatment of vitiligo in children and adolescents by autologous cultured pure
      melanocytes transplantation with comparison of efficacy to results in adults.
AB  - BACKGROUND: Transplantation of autologous cultured pure melanocytes is a well
      established procedure for the treatment of refractory and stabilized vitiligo.
      However, there was no report specifically comparing the efficacy with the regard
      to defined age groups (children-adolescence-adult). OBJECTIVE:   We analysed the
      efficacy of this procedure in the treatment of vitiligo in children and
      adolescents and compare it with the results in adults treated during the same
      period and using identical procedures. METHODS: Melanocytes were isolated from
      the roof of suction blister, cultured and expanded with Hu16 medium in vitro, and
      transplanted to laser-denuded receipt area. A total of 12 children (8-12 years),
      20 adolescents (13-17 years) and 70 adults with vitiligo were treated using this
      procedure. RESULTS: The patients obtained satisfactory results (repigmentation of
      50% or more) results in children, adolescents and adults were 83.3%, 95.0% and
      84.0% respectively. The mean extent of repigmentation in children, adolescents
      and adults was 80.7%, 78.9% and 76.6% respectively. There was no statistical
      difference in repigmentation among these three groups. After adjusting for all
      factors (gender, type of vitiligo, period of stability, location of the lesion or
      transplanted cell density) individually or totally using multiple regression
      analysis, age still did not correlate to the extent of repigmentation.
      CONCLUSIONS: The satisfactory results obtained in the treatment of vitiligo in
      children and adolescents by transplantation of cultured autologous pure
      melanocytes are comparable with the results in adults. Therefore, this procedure
      can be considered in refractory and stable vitiligo in children and adolescents,
      especially in patients with large vitiliginous lesions.

PMID- 20673301
TI  - Vasopressin protects hippocampal neurones in culture against nutrient deprivation
      or glutamate-induced apoptosis.
AB  - Vasopressin (VP) secreted within the brain modulates neuronal function by acting
      as a neurotransmitter. Recent studies show that VP prevents serum deprivation
      induced apoptosis in the neuronal cell line, H32. To determine whether VP is anti
      apoptotic in hippocampal neurones, primary cultures of these neurones were used
      to examine the effect of VP on neuronal culture supplement (B27) deprivation-, or
      glutamate-induced apoptosis, and the signalling pathways mediating the effects.
      Removal of B27 supplement from the culture medium for 24 h or the addition of
      glutamate (3-10MUm) decreased neuronal viability (P<0.05) and increased Tdt
      mediated dUTP nick-end labelling (TUNEL) staining and caspase-3 activity
      (P<0.05), which is consistent with apoptotic cell death. VP (10 nm) reduced B27
      deprivation- or glutamate-induced cell death (P<0.05). These anti-apoptotic
      effects of VP were completely blocked by a V1 but not a V2 receptor antagonist,
      indicating that they are mediated via V1 VP receptors. The anti-apoptotic effect
      of VP in neurones involves activation of mitogen-activated protein kinase
      (MAPK)/extracellular signal-regulated kinase (ERK) and inositol
      trisphosphate/protein kinase B (Akt) signalling pathways. This was shown by the
      transient increases in phospho-ERK and phospho-Akt after incubation with VP
      revealed by western blot analyses, and the ability of specific inhibitors to
      reduce the inhibitory effect of VP on caspase-3 activity and TUNEL staining by
      70% and 35%, respectively (P<0.05). These studies demonstrate that VP has anti
      apoptotic actions in hippocampal neurones, an effect that is mediated by the
      MAPK/ERK and phosphatidylinositol-3 kinase/Akt signalling pathways. The ability
      of VP to reduce nutrient deprivation or glutamate overstimulation-induced
      neuronal death suggests that VP acts as a neuroprotective agent within the brain.

PMID- 20673304
TI  - Objective and non-invasive evaluation of photorejuvenation effect with intense
      pulsed light treatment in Asian skin.
AB  - BACKGROUND: Intense pulsed light (IPL) has been widely used for
      photorejuvenation. Although previous literature has shown clinical effectiveness
      of IPL treatments on cutaneous photoaging, the associated changes in the
      biophysical properties of the skin following IPL treatments have not been fully
      elucidated. OBJECTIVE: The aim of this study was to evaluate changes in skin
      biophysical properties in patients with photoaging after IPL treatments, using
      non-invasive, objective skin measuring devices. PATIENTS AND METHODS: A total of
      26 Korean women with facial dyschromias underwent three sessions of IPL treatment
      at 4-week intervals. Outcome assessments included standardized photography,
      global evaluation by blinded investigators, patients' self-assessment and
      objective measurements of colour (Mexameter MX18, Chromatometer), elasticity
      (Cutometer), roughness (Visiometer), sebum (Sebumeter) and skin hydration
      (Corneometer). Results  Intense pulsed light treatments produced a 15% decrease
      in the size of representative pigmented lesions (P < 0.05). Patients' self
      assessment revealed that 84% and 58% of subjects considered their pigmented
      lesions and wrinkles were improved respectively. Objective colorimetric
      measurement demonstrated significant improvements following IPL treatments that
      were most remarkable after one session of IPL. Moreover, skin elasticity showed
      significant improvements at the end of the study. Skin wrinkles as measured using
      Visiometer showed a mild improvement without statistical significance. Sebum
      secretion and water content of skin remained unchanged. CONCLUSIONS: Intense
      pulsed light provided significant improvement in the appearance of facial
      pigmented lesions in Korean patients. These effects appeared to be more
      remarkable in improving pigmentation, skin tone and elasticity.

PMID- 20673305
TI  - Etanercept: effectiveness and safety data of a retrospective study.

PMID- 20673306
TI  - Cellulite, smoking and angiotensin-converting enzyme (ACE) gene
      insertion/deletion polymorphism.

PMID- 20673307
TI  - Patients' experience of pain and pain relief following hip replacement surgery.
AB  - AIMS: The aim of this study was to describe patients' experience of pain and pain
      relief following hip replacement surgery. BACKGROUND: Annually, many patients
      undergo hip replacement surgery. Previous research has focused largely on the
      long-term effects on pain for patients who undergo hip replacement surgery and to
      a lesser degree on their subjective, early postoperative pain experience. DESIGN:
      A descriptive qualitative design was used. METHODS: The study was carried out in
      an orthopaedic ward at a hospital in Sweden during 2006. Qualitative interviews
      were conducted with 15 patients who had undergone hip replacement surgery. Data
      were analysed by means of qualitative content analysis. RESULTS: The
      postoperative pain experience was characterised in terms of interrelated contexts
      of time, various bodily activities and postoperative pain intensity. The
      postoperative pain intensity was characterised in terms of intensive and worst
      imaginable, strange feelings and fear and a feeling of faintness. Easing of
      postoperative pain was related to professional care features, such as nursing
      staff, pharmacological pain relief and technical aids. Self-care features were
      related to relieving body positions, endurance and looking ahead. CONCLUSION:
      Although the development of total hip replacement surgery has been very
      successful, there are issues that need to be addressed in relation to
      postoperative pain management. The findings in this study show that there are
      reasons for making a more concerted effort to develop postoperative pain
      management, particularly during the first few days after surgery. RELEVANCE TO
      CLINICAL PRACTICE: The results provide some indication that pain management for
      this group of patients in the early postoperative period needs to be improved to
      reduce the fear of moving and improve the process of regaining independence.
      Devoting more attention to the patients during the initial postoperative phase
      may be the key to improve the training and making it even more effective.

PMID- 20673308
TI  - Low back pain and work-related factors among nurses in intensive care units.
AB  - AIM: To examine the relationship of low back pain prevalence and treatment to
      personal and work-related characteristics among intensive care unit nurses.
      BACKGROUND: Back pain is the most common work-related health problem among
      nurses. DESIGN: A cross-sectional study including a survey conducted in 2007.
      METHODS: The study sample included 1345 nurses in 65 intensive care units in 22
      South Korean hospitals. Back pain prevalence was measured by the frequency of
      back pain (always, once a week, once a month or once in two or more months)
      during the past year. Multilevel logistic regression analyses were conducted to
      examine the relationship between back pain and personal and work-related
      characteristics. RESULTS: The mean age of nurses was 27.2 years. Overall, 90.3%
      of nurses had back pain at least once a month (21.9% always, 40.7% once a week
      and 27.7% once a month). Only 18.3% had received medical treatment for their back
      pain. Compared with neonatal intensive care unit nurses, who had the lowest
      prevalence, nurses in other specialties, excluding paediatric intensive care
      units, had a greater likelihood of back pain. Specialty medical (e.g. cardiology,
      neurology) intensive care unit nurses had the greatest probability of back pain
      and treatment. Perceiving staffing as inadequate and working 6 or more night
      shifts per month were related to a 64% increase (OR = 1.64; 95% CI =1.16-2.33)
      and 48% increase (OR =1.48; 95% CI = 1.10-1.99) in back pain, respectively.
      Nurses with 2-4 years of working experience in intensive care units had the
      greatest probability of back pain and treatment. CONCLUSIONS: A high prevalence
      of back pain was found in intensive care unit nurses, even though they comprise a
      very young workforce in Korea. RELEVANCE TO CLINICAL PRACTICE: Improving nurse
      staffing, reducing the frequency of night shifts and assessing risk factors in
      specific intensive care unit specialties are suggested to decrease back pain
      prevalence.

PMID- 20673309
TI  - Relationship between an increased serum kynurenine/tryptophan ratio and
      atherosclerotic parameters in hemodialysis patients.
AB  - Essential amino acid tryptophan (Trp) is mainly catabolized by indoleamine 2,3
      dioxygenase, which leads to the formation of kynurenine (Kyn). In this study, we
      reexamined whether an increased indoleamine 2,3-dioxygenase activity, as
      estimated by the Kyn/Trp ratio (MUM/mM), is associated with atherosclerotic
      parameters in hemodialysis (HD) patients. Serum Trp and Kyn were measured in 243
      HD patients by liquid chromatography/electrospray ionization tandem mass
      spectrometry. We measured carotid artery intima-medial thickness, brachial-ankle
      pulse wave velocity, ankle-brachial pressure index, and the cardio-ankle vascular
      index. Log-transformed Kyn/Trp ratio was significantly correlated with log
      transformed time on HD (rho=0.28, P<0.01), log-transformed highly sensitive C
      reactive protein (rho=0.20, P<0.01), and peripheral total lymphocyte count (rho=
      0.13, P<0.05). A significant association was found between log-transformed
      Kyn/Trp ratio and mean carotid artery intima-medial thickness (rho=0.18, P<0.01).
      Mean carotid artery intima-medial thickness was significantly higher in the
      lowest quartile of Kyn/Trp ratio (<165) (0.62+/-0.12 mm) when compared with the
      highest quartile (>=304) (0.68+/-0.15 mm) (P<0.01). Ankle-brachial pressure index
      was lower in the second quartile (1.01+/-0.20), the third quartile (1.01+/-0.19),
      and the fourth quartile (1.03+/-0.15) compared with that in the first quartile
      (1.09+/-0.13) (P<0.05). It follows from these findings that the Kyn/Trp ratio
      increases with time on HD, and is associated with advanced atherosclerotic
      changes in chronic HD patients.

PMID- 20673310
TI  - Forelimb dyskinesia mediated by high-frequency stimulation of the subthalamic
      nucleus is linked to rapid activation of the NR2B subunit of N-methyl-D-aspartate
      receptors.
AB  - Dyskinesia is a major side-effect of chronic l-DOPA administration, the reference
      treatment for Parkinson's disease. High-frequency stimulation of the subthalamic
      nucleus (STN-HFS) alleviates parkinsonian motor symptoms and indirectly improves
      dyskinesia by decreasing the L-DOPA requirement. However, inappropriate
      stimulation can also trigger dyskinetic movements, in both human and rodents. We
      investigated whether STN-HFS-evoked forelimb dyskinesia involved changes in
      glutamatergic neurotransmission as previously reported for L-DOPA-induced
      dyskinesias, focusing on the role of NR2B-containing N-methyl-D-aspartate
      receptors (NR2B/NMDARs). We applied STN-HFS in normal rats at intensities above
      and below the threshold for triggering forelimb dyskinesia. Dyskinesiogenic STN
      HFS induced the activation of NR2B (as assessed by immunodetection of the
      phosphorylated residue Tyr(1472)) in neurons of the subthalamic nucleus,
      entopeduncular nucleus, motor thalamus and forelimb motor cortex. The severity of
      STN-HFS-induced forelimb dyskinesia was decreased in a dose-dependent manner by
      systemic injections of CP-101,606, a selective blocker of NR2B/NMDARs, but was
      either unaffected or increased by the non-selective N-methyl-D-aspartate receptor
      antagonist, MK-801.

PMID- 20673311
TI  - Functional identification of an outwardly rectifying pH- and anesthetic-sensitive
      leak K(+) conductance in hippocampal astrocytes.
AB  - Astrocytes function as spatial K(+) buffers by expressing a rich repertoire of
      K(+) channels. Earlier studies suggest that acid-sensitive tandem-pore K(+)
      channels, mainly TWIK-related acid-sensitive K(+) (TASK) channels, mediate part
      of the passive astroglial membrane conductance. Here, using a combination of
      electrophysiology and pharmacology, we investigated the presence of TASK-like
      conductance in hippocampal astrocytes of rat brain slices. Extracellular pH
      shifts to below 7.4 (or above 7.4) induced a prominent inward (or outward)
      current in astrocytes in the presence of tetrodotoxin, a Na(+) channel blocker,
      and 4,4'-diisothiocyanatostilbene-2,2'-disulfonate, a co-transporter blocker. The
      pH-sensitive current was insensitive to quinine, a potent blocker of tandem-pore
      K(+) channels including TWIK-1 and TREK-1 channels. Voltage-clamp analysis
      revealed that the pH-sensitive current exhibited weak outward rectification with
      a reversal potential of -112 mV, close to the Nernst equilibrium potential for
      K(+) . Furthermore, the current-voltage relationship was well fitted with the
      Goldman-Hodgkin-Katz current equation for the classical open-rectifier 'leak'
      K(+) channel. The pH-sensitive K(+) current was potentiated by TASK channel
      modulators such as the volatile anesthetic isoflurane but depressed by the local
      anesthetic bupivacaine. However, unlike TASK channels, the pH-sensitive current
      was insensitive to Ba(2+) and quinine. Thus, the molecular identity of the pH
      sensitive leak K(+) channel is unlikely to be attributable to TASK channels.
      Taken together, our results suggest a novel yet unknown leak K(+) channel
      underlying the pH- and anesthetic-sensitive background conductance in hippocampal
      astrocytes.

PMID- 20673312
TI  - Signaling through erbB receptors is a critical functional regulator in the mature
      cochlea.
AB  - Noise, ototoxic substances and various genetic factors are common causes of
      profound hearing loss. Cochlear implants can often restore hearing in these
      cases, but only if a sufficient number of responsive auditory nerve fibers
      remain. Over time, these nerve fibers degenerate in the damaged ear, and it is
      therefore important to establish factors that control neuronal survival and
      maintain neural excitability. Recent studies show that neuregulins and their
      receptors are important for survival and proper targeting of neurons in the
      developing inner ear. A role for neuregulins as maintainers of the neuronal
      population in the mature inner ear was therefore hypothesized. Here, this
      hypothesis was directly tested by chronic local application of substances that
      block neuregulin receptors. Using auditory brainstem response measurements, we
      demonstrate that such receptor block leads to a progressive hearing impairment
      that develops over the course of weeks. This impairment occurs despite a normal
      number of auditory neurons and preserved outer hair cell function. Real-time
      quantitative reverse transcriptase-polymerase chain reaction shows alterations in
      neurotrophin-3 expression, suggesting that this growth factor participates in
      regulating cochlear sensitivity. The present work demonstrates the critical
      importance of neuregulin/erbB signaling in long-term functional regulation in the
      mature guinea pig hearing organ.

PMID- 20673313
TI  - Identification and characterization of Cs(+) -permeable K(+) channel current in
      mouse cerebellar Purkinje cells in lobules 9 and 10 evoked by molecular layer
      stimulation.
AB  - The mouse cerebellum consists of 10 lobules, which are distinguishable by their
      anatomical and functional properties. However, the differences in the slow
      postsynaptic currents (sPSCs) of Purkinje cells between lobules have not been
      well studied. We recorded the sPSCs of lobules 3, 9 and 10 evoked by tetanic
      stimulation of the molecular layer in cerebellar slices, and found a novel
      outward sPSC mediated by the GABA(B) receptor in loblues 9 and 10 but hardly at
      all in lobule 3. We showed that the lobule-specific difference is at least partly
      attributable to differences in the density of GABAergic neurons (higher in lobule
      10 than in lobules 3 and 9), and the functional expression level of postsynaptic
      GABA(B) receptor currents (larger in lobules 9 and 10 than in lobule 3). The G
      protein-coupled inward rectifying K(+) channel (GIRK) is known to be activated by
      GABA(B) receptors; however, the outward sPSC was not blocked by a GIRK blocker,
      was not sensitive to Cs(+) block, and was observed when Cs(+) was used as a
      charge carrier. These results suggest that a K(+) channel other than GIRK could
      be activated by GABA(B) receptors. KCNK13 is a Cs(+)-permeable K(+) channel that
      shows intense expression of mRNA in Purkinje cells. KCNK13 current was enhanced
      by co-expression of G(betagamma) subunits and was observed when Cs(+) was used as
      a charge carrier in heterologous expression systems, and the amino acids critical
      for these features were identified by mutagenesis. Taken together, these results
      show that KCNK13 is a legitimate candidate for the Cs(+)-permeable K(+) channel
      activated by GABA(B) receptors, presumably via G(betagamma) subunits in Purkinje
      cells.

PMID- 20673314
TI  - Addressing poverty, education, and gender equality to improve the health of women
      worldwide.
AB  - The Millennium Development Goals (MDG) that target alleviating poverty, improving
      primary education, and fostering gender equity are important as a foundation to
      promote world health. Achieving these goals will create an environment for
      healthy lives for women and children. Poverty, education, and gender equality,
      although undeniably linked, need to be addressed individually. Nurses have the
      capacity and political will to address MDGs and to contribute to the health and
      well-being of the world population.

PMID- 20673315
TI  - Millennium development goals and global women's and infants' health.
AB  - This article presents a brief history and description of the Millennium
      Development Goals (MDGs) as a framework for addressing the world's health needs.
      They focus on decreasing poverty, decreasing child and maternal mortality, and
      ensuring gender equality in terms of education, work opportunities, and health
      and health care. Progress on attainment of MDGs is reported, and links between
      social determinants of health and the well-being of women and newborns are
      presented. Implications for maternal newborn nurses are discussed.

PMID- 20673316
TI  - Millennium development goals and global health of women and newborns.

PMID- 20673317
TI  - Sustaining the vision for Millennium Development Goal 6, to halt and reverse the
      spread of HIV/AIDS and other infections.
AB  - The purpose of Millennium Development Goal 6 is to halt and reverse the spread of
      HIV/AIDS, malaria, and other diseases and provide universal access to treatment
      for HIV/AIDS. In this article we describe progress made in meeting the targets
      for HIV/AIDS set for 2015 and the President's Emergency Plan for AIDS Relief.
      This funding is geared toward developing sustainable solutions with which to
      combat diseases that threaten our global community.

PMID- 20673318
TI  - Achieving Millennium Development Goal 5, the improvement of maternal health.
AB  - The purpose of this article is to describe the progress made toward the
      achievement of Millennium Development Goal 5, the improvement of maternal health.
      Maternal mortality rates (MMR) remain high globally, and in the United States
      there have been recent increases in MMR. Interventions to improve global maternal
      health are described. Nurses should be aware of the enduring epidemic of global
      maternal mortality, advocate for childbearing women, and contribute to
      implementing effective interventions to reduce maternal mortality.

PMID- 20673319
TI  - Descriptive study of 32 cases of doxycycline-overdosed calves.
AB  - BACKGROUND: Reports of doxycycline-induced toxicity are limited despite common
      use of this antibiotic to treat infectious respiratory disorders in calves.
      OBJECTIVE: To describe previously unreported kidney lesions and diagnostic test
      results in doxycycline-overdosed calves and to compare these results with other
      findings reported previously. ANIMALS: Thirty-two calves that presented with
      adverse effects after receiving high doses of doxycycline as a treatment for mild
      respiratory disorders. METHOD: Retrospective review of medical records. RESULTS:
      Clinical examination identified mainly lethargy, dyspnea, cough, tongue paresia
      or paralysis associated with dysphagia and sialorrhea, tachycardia, tachypnea,
      and signs of myopathy. Blood analysis indicated increases in creatine kinase,
      lactate dehydrogenase, aspartate aminotransferase, and sorbitol dehydrogenase
      activities and increased serum creatinine and urea concentrations. ECG recordings
      and Doppler echocardiography examination identified ventricular premature beats
      and a decrease in left ventricular global and systolic function, respectively.
      Necropsy and histopathology disclosed necrosis of the myocardium, tongue, and
      some striated muscles, acute renal tubular necrosis, and fatty degeneration or
      congestion of the liver. CONCLUSIONS: Most of these findings corroborate previous
      observations made in doxycycline-overdosed calves, and further suggest myocardial
      and striated muscular toxicity as well as renal toxicity in doxycycline-overdosed
      calves.

PMID- 20673320
TI  - Neurogenic diabetes insipidus presenting in a patient with subacute liver
      failure: a case report.
AB  - INTRODUCTION: To the best of our knowledge, this is the first report in the
      literature of development of neurogenic diabetes insipidus in a patient with
      subacute liver failure. CASE PRESENTATION: A 25-year-old man presented with
      subacute liver failure. While awaiting a liver transplant, the patient developed
      cerebral edema, which resulted in neurogenic diabetes insipidus secondary to
      cerebral edema. The patient died before the liver transplantation could be
      carried out. CONCLUSION: Neurogenic diabetes insipidus is well recognized in the
      neurosurgical population as a consequence of cerebral edema and increased
      intracranial pressure, both of which occur commonly in patients with subacute
      liver failure.

PMID- 20673321
TI  - RuleMonkey: software for stochastic simulation of rule-based models.
AB  - BACKGROUND: The system-level dynamics of many molecular interactions,
      particularly protein-protein interactions, can be conveniently represented using
      reaction rules, which can be specified using model-specification languages, such
      as the BioNetGen language (BNGL). A set of rules implicitly defines a
      (bio)chemical reaction network. The reaction network implied by a set of rules is
      often very large, and as a result, generation of the network implied by rules
      tends to be computationally expensive. Moreover, the cost of many commonly used
      methods for simulating network dynamics is a function of network size. Together
      these factors have limited application of the rule-based modeling approach.
      Recently, several methods for simulating rule-based models have been developed
      that avoid the expensive step of network generation. The cost of these "network
      free" simulation methods is independent of the number of reactions implied by
      rules. Software implementing such methods is now needed for the simulation and
      analysis of rule-based models of biochemical systems. RESULTS: Here, we present a
      software tool called RuleMonkey, which implements a network-free method for
      simulation of rule-based models that is similar to Gillespie's method. The method
      is suitable for rule-based models that can be encoded in BNGL, including models
      with rules that have global application conditions, such as rules for
      intramolecular association reactions. In addition, the method is rejection free,
      unlike other network-free methods that introduce null events, i.e., steps in the
      simulation procedure that do not change the state of the reaction system being
      simulated. We verify that RuleMonkey produces correct simulation results, and we
      compare its performance against DYNSTOC, another BNGL-compliant tool for network
      free simulation of rule-based models. We also compare RuleMonkey against problem
      specific codes implementing network-free simulation methods. CONCLUSIONS:
      RuleMonkey enables the simulation of rule-based models for which the underlying
      reaction networks are large. It is typically faster than DYNSTOC for benchmark
      problems that we have examined. RuleMonkey is freely available as a stand-alone
      application http://public.tgen.org/rulemonkey. It is also available as a
      simulation engine within GetBonNie, a web-based environment for building,
      analyzing and sharing rule-based models.

PMID- 20673322
TI  - The mental health of populations directly and indirectly exposed to violent
      conflict in Indonesia.
AB  - BACKGROUND: Large disasters affect people who live both near and far from the
      areas in which they occur. The mental health impact is expected to be similar to
      a ripple effect, where the risk of mental health consequences generally decreases
      with increasing distance from the disaster center. However, we have not been able
      to identify studies of the ripple effect of man-made disaster on mental health in
      low-income countries. OBJECTIVES: The objective was to examine the hypothesis of
      a ripple effect on the mental health consequences in populations exposed to man
      made disasters in a developing country context, through a comparison of two
      different populations living in different proximities from the center of disaster
      in Mollucas. METHODS: Cross-sectional longitudinal data were collected from 510
      Internally Displaced Persons (IDPs) living in Ambon, who were directly exposed to
      the violence, and non-IDPs living in remote villages in Mollucas, Indonesia, who
      had never been directly exposed to violence in Mollucas. Data were collected
      during home visits and statistical comparisons were conducted by using chi square
      tests, t-test and logistic regression. RESULTS: There was significantly more
      psychological distress "caseness" in IDPs than non-IDPs. The mental health
      consequences of the violent conflict in Ambon supported the ripple effect
      hypothesis as displacement status appears to be a strong risk factor for
      distress, both as a main effect and interaction effect. Significantly higher
      percentages of IDPs experienced traumatic events than non-IDPs in all six event
      types reported. CONCLUSIONS: This study indicates that the conflict had an impact
      on mental health and economic conditions far beyond the area where the actual
      violent events took place, in a diminishing pattern in line with the hypothesis
      of a ripple effect.

PMID- 20673323
TI  - Enhancing cytotoxic and apoptotic effect in OVCAR-3 and MDAH-2774 cells with all
      trans retinoic acid and zoledronic acid: a paradigm of synergistic molecular
      targeting treatment for ovarian cancer.
AB  - BACKGROUND: Ovarian cancer is the most fatal gynecologic malignancies in the
      world. Although, platinum based treatments are widely used, the disease becomes
      treatment refractory within two years, and novel treatment options should be
      searched. All- trans retinoic acid (ATRA) induces growth arrest, differentiation
      and cell death in some types of cancer cells and its combination with various
      anticancer agents results in enhanced cytotoxicity. Zoledronic acid is a common
      bisphosphonate known for its anticancer effects beyond its current use in the
      treatment of cancer-induced bone disease. We aimed to investigate the possible
      additive/synergistic effect of both agents in OVCAR-3 and MDAH-2774 ovarian
      cancer cell lines, since both agents show superiority to conventional cytotoxics
      in terms of adverse events. METHODS: XTT cell proliferation assay was used for
      showing cytotoxicity. For verifying apoptosis, both DNA Fragmentation by ELISA
      assay and caspase 3/7 activity measurement were used. OligoGeArray which consists
      of 112 apoptosis related genes was used to elucidate the genetic changes within
      cancer cells. To validate our oligoarray results, quantitative real-time PCR was
      performed on four selected genes that were maximally effected by the combination
      treatment: lymphotoxin beta receptor (LTBR), myeloid cell leukemia-1 (MCL-1),
      tumor necrosis factor receptor superfamily, member 1A (TNFRSF1A), TNFRSF1A
      associated death domain protein (TRADD). RESULTS: We demonstrated that a novel
      combination of ATRA and zoledronic acid is a strong inducer of apoptotic related
      cell death in both ovarian cancer cells. While the combination therapy
      significantly induced proapoptotic genes such as tumor necrosis factor receptor
      superfamily (TNFRSF), TRADD and caspase 4, some of the antiapoptotic genes such
      as members of MCL-1, LTBR, BAG3 and Bcl-2 family members were inhibited.
      CONCLUSIONS: These are the preliminary molecular results of a novel combination
      treatment of ATRA and zoledronic acid, with fewer side effects as compared to
      conventional cytotoxic agents. With additional experimental analysis, it may
      serve as a good option for the treatment of refractory and elderly ovarian cancer
      patients, for whom there exists very limited choice of treatment.

PMID- 20673324
TI  - Persistent alveolar soft-part sarcoma with liver metastasis: a case report.
AB  - INTRODUCTION: Alveolar soft-part sarcomas are rare, slow-growing tumors that
      metastasize commonly via vascular routes to the lungs, bones, lymph nodes and
      brain, causing morbidity and mortality. To the best of our knowledge, this is the
      first case describing metastasis to the liver reported from Nigeria. CASE
      PRESENTATION: A 57-year-old man of the Urhobo ethnic group of Nigeria presented
      with a persistent mass in his left calf. It was initially diagnosed as soft
      tissue sarcoma, and its associated systemic effects lead to his death before a
      histological diagnosis could be obtained. CONCLUSIONS: Alveolar soft-part sarcoma
      with metastasis to the liver can occur in our region (northeast Africa), and a
      high index of suspicion is required to make an early diagnosis, followed by
      prompt surgical excision with clear margins in order to prevent mortality.

PMID- 20673326
TI  - End-of-life care in Germany: Study design, methods and first results of the EPACS
      study (Establishment of Hospice and Palliative Care Services in Germany).
AB  - BACKGROUND: In order to tackle the deficits in the provision of palliative home
      care, profound structural changes in the outpatient sector were introduced by law
      in Germany in 2007. The EPACS study was carried out (Research Accompanying the
      Establishment of Hospice and Palliative Care Services in Rhineland-Palatinate,
      Germany) to document the quality of inpatient and outpatient end-of-life care in
      Rhineland-Palatinate, Germany, before the implementation of these changes. With
      this article we focus on the study design and methods of the EPACS-Study. We
      further report first results regarding several aspects of outpatient end-of-life
      care. METHODS: The cross-sectional survey was based on a random sample of 5000
      inhabitants of Rhineland-Palatinate that had died from May 25 until August 24 of
      the year 2008. Relatives of these randomly drawn deceased persons were
      interviewed by means of a written survey. RESULTS: The overall response
      proportion considering only those questionnaires that actually were delivered (n
      = 3833) was 36.0%. Factors influencing participation were age, sex, and marital
      status. 355 (25.8%) deceased persons had used professional home care in the four
      weeks prior to their death, but only very few persons had used a specialised
      palliative home care service (n = 30; 8.5%). There was a clear gap between the
      need for specialised outpatient care and the actual utilisation of these
      services. CONCLUSIONS: Satisfaction with professional home care was relatively
      high, but physicians were rated less favourable than nurses. There were deficits
      especially with respect to physicians' communicative and supportive skills.
      Further analyses are necessary to provide more detailed information about quality
      of care in different care settings and for distinct groups. Predictors of good
      care, as well as obstacles to it, must be further investigated. In the long run,
      a follow-up survey must be conducted to compare quality of home care before and
      after the structural changes in Germany.

PMID- 20673327
TI  - Synergy of combined doxycycline/TUDCA treatment in lowering Transthyretin
      deposition and associated biomarkers: studies in FAP mouse models.
AB  - Familial Amyloidotic Polyneuropathy (FAP) is a disorder characterized by the
      extracellular deposition of fibrillar Transthyretin (TTR) amyloid, with a special
      involvement of the peripheral nerve. We had previously shown that doxycycline
      administered for 3 months at 40 mg/Kg/ml in the drinking water, was capable of
      removing TTR amyloid deposits present in stomachs of old TTR-V30M transgenic
      mice; the removal was accompanied by a decrease in extracellular matrix
      remodeling proteins that accompany fibrillar deposition, but not of non-fibrillar
      TTR deposition and/or markers associated with pre-fibrillar deposits. On the
      other hand, Tauroursodeoxycholic acid (TUDCA), a biliary acid, administrated to
      the same mouse model was shown to be effective at lowering deposited non
      fibrillar TTR, as well as the levels of markers associated with pre-fibrillar
      TTR, but only at young ages. In the present work we evaluated different
      doxycycline administration schemes, including different periods of treatment,
      different dosages and different FAP TTR V30M animal models. Evaluation included
      CR staining, immunohistochemistry for TTR, metalloproteinase 9 (MMP-9) and serum
      amyloid P component (SAP). We determined that a minimum period of 15 days of
      treatment with a 8 mg/Kg/day dosage resulted in fibril removal. The possibility
      of intermittent treatments was also assessed and a maximum period of 15 days of
      suspension was determined to maintain tissues amyloid-free. Combined cycled
      doxycycline and TUDCA administration to mice with amyloid deposition, using two
      different concentrations of both drugs, was more effective than either individual
      doxycycline or TUDCA, in significantly lowering TTR deposition and associated
      tissue markers. The observed synergistic effect of doxycycline/TUDCA in the range
      of human tolerable quantities, in the transgenic TTR mice models prompts their
      application in FAP, particularly in the early stages of disease.

PMID- 20673325
TI  - EDUCORE project: a clinical trial, randomised by clusters, to assess the effect
      of a visual learning method on blood pressure control in the primary healthcare
      setting.
AB  - BACKGROUND: High blood pressure (HBP) is a major risk factor for cardiovascular
      disease (CVD). European hypertension and cardiology societies as well as expert
      committees on CVD prevention recommend stratifying cardiovascular risk using the
      SCORE method, the modification of lifestyles to prevent CVD, and achieving good
      control over risk factors. The EDUCORE (Education and Coronary Risk Evaluation)
      project aims to determine whether the use of a cardiovascular risk visual
      learning method--the EDUCORE method--is more effective than normal clinical
      practice in improving the control of blood pressure within one year in patients
      with poorly controlled hypertension but no background of CVD; METHODS/DESIGN:
      This work describes a protocol for a clinical trial, randomised by clusters and
      involving 22 primary healthcare clinics, to test the effectiveness of the EDUCORE
      method. The number of patients required was 736, all between 40 and 65 years of
      age (n = 368 in the EDUCORE and control groups), all of whom had been diagnosed
      with HBP at least one year ago, and all of whom had poorly controlled
      hypertension (systolic blood pressure >or= 140 mmHg and/or diastolic >or= 90
      mmHg). All personnel taking part were explained the trial and trained in its
      methodology. The EDUCORE method contemplates the visualisation of low risk SCORE
      scores using images embodying different stages of a high risk action, plus the
      receipt of a pamphlet explaining how to better maintain cardiac health. The main
      outcome variable was the control of blood pressure; secondary outcome variables
      included the SCORE score, therapeutic compliance, quality of life, and total
      cholesterol level. All outcome variables were measured at the beginning of the
      experimental period and again at 6 and 12 months. Information on sex, age,
      educational level, physical activity, body mass index, consumption of
      medications, change of treatment and blood analysis results was also recorded;
      DISCUSSION: The EDUCORE method could provide a simple, inexpensive means of
      improving blood pressure control, and perhaps other health problems, in the
      primary healthcare setting; TRIAL REGISTRATION: The trial was registered with
      ClinicalTrials.gov, number NCT01155973 [http://ClinicalTrials.gov].

PMID- 20673328
TI  - Prognostic significance of TRAIL death receptors in Middle Eastern colorectal
      carcinomas and their correlation to oncogenic KRAS alterations.
AB  - BACKGROUND: Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a
      member of the tumour necrosis factor cytokine family that induces apoptosis upon
      binding to its death domain containing receptors, TRAIL receptor 1 (DR4) and
      TRAIL receptor 2 (DR5). Expression of TRAIL receptors is higher in colorectal
      carcinoma (CRC) as compared to normal colorectal mucosa and targeted therapy with
      TRAIL leads to preferential killing of tumor cells sparing normal cells. METHODS:
      We investigated the expression of TRAIL and its receptors in a tissue microarray
      cohort of 448 Middle Eastern CRC. We also studied the correlation between TRAIL
      receptors and various clinico-pathological features including key molecular
      alterations and overall survival. RESULTS: CRC subset with TRAIL-R1 expression
      was associated with a less aggressive phenotype characterized by early stage (p =
      0.0251) and a histology subtype of adenocarcinomas (p = 0.0355). Similarly CRC
      subset with TRAIL-R2 expression was associated with a well-differentiated tumors
      (p < 0.0001), histology subtype of adenocarcinomas (p = 0.0010) and tumors in
      left colon (p = 0.0009). Over expression of pro apoptotic markers: p27KIP1 and
      KRAS4A isoforms was significantly higher in CRC subset with TRAIL-R1 and TRAIL-R2
      expression; TRAIL-R1 expression was also associated with cleaved caspase-3(p =
      0.0011). Interestingly, TRAIL-R2 expression was associated with a microsatellite
      stable (MS--S/L) phenotype (p = 0.0003) and with absence of KRAS mutations (p =
      0.0481). CONCLUSION: TRAIL-R1 expression was an independent prognostic marker for
      better survival in all CRC samples and even in the CRC group that received
      adjuvant therapy. The biological effects of TRAIL in CRC models, its enhancement
      of chemosensitivity towards standard chemotherapeutic agents and the effect of
      endogenous TRAIL receptor levels on survival make TRAIL an extremely attractive
      therapeutic target.

PMID- 20673329
TI  - A renewed focus on primary health care: revitalize or reframe?
AB  - The year 2008 celebrated 30 years of Primary Health Care (PHC) policy emerging
      from the Alma Ata Declaration with publication of two key reports, the World
      Health Report 2008 and the Report of the Commission on the Social Determinants of
      Health. Both reports reaffirmed the relevance of PHC in terms of its vision and
      values in today's world. However, important challenges in terms of defining PHC,
      equity and empowerment need to be addressed.This article takes the form of a
      commentary reviewing developments in the last 30 years and discusses the future
      of this policy. Three challenges are put forward for discussion (i) the challenge
      of moving away from a narrow technical bio-medical paradigm of health to a
      broader social determinants approach and the need to differentiate primary care
      from primary health care; (ii) The challenge of tackling the equity implications
      of the market oriented reforms and ensuring that the role of the State in the
      provision of welfare services is not further weakened; and (iii) the challenge of
      finding ways to develop local community commitments especially in terms of
      empowerment.These challenges need to be addressed if PHC is to remain relevant in
      today's context. The paper concludes that it is not sufficient to revitalize PHC
      of the Alma Ata Declaration but it must be reframed in light of the above
      discussion.

PMID- 20673330
TI  - Preliminary study into the components of the fear-avoidance model of LBP: change
      after an initial chiropractic visit and influence on outcome.
AB  - BACKGROUND: In the last decade the sub grouping of low back pain (LBP) patients
      according to their likely response to treatment has been identified as a research
      priority. As with other patient groups, researchers have found few if any factors
      from the case history or physical examination that are helpful in predicting the
      outcome of chiropractic care. However, in the wider LBP population psychosocial
      factors have been identified that are significantly prognostic. This study
      investigated changes in the components of the LBP fear-avoidance beliefs model in
      patients pre- and post- their initial visit with a chiropractor to determine if
      there was a relationship with outcomes at 1 month. METHODS: Seventy one new
      patients with lower back pain as their primary complaint presenting for
      chiropractic care to one of five clinics (nine chiropractors) completed
      questionnaires before their initial visit (pre-visit) and again just before their
      second appointment (post-visit). One month after the initial consultation,
      patient global impression of change (PGIC) scores were collected. Pre visit and
      post visit psychological domain scores were analysed for any association with
      outcomes at 1 month. RESULTS: Group mean scores for Fear Avoidance Beliefs (FAB),
      catastrophisation and self-efficacy were all improved significantly within a few
      days of a patient's initial chiropractic consultation. Pre-visit
      catastrophisation as well as post-visit scores for catastrophisation, back
      beliefs (inevitability) and self-efficacy were weakly correlated with patient's
      global impression of change (PGIC) at 1 month. However when the four assessed
      psychological variables were dichotomised about pre-visit group medians those
      individuals with 2 or more high variables post-visit had a substantially
      increased risk (OR 36.4 (95% CI 6.2-213.0) of poor recovery at 1 month. Seven
      percent of patients with 1 or fewer adverse psychological variables described
      poor benefit compared to 73% of those with 2 or more. CONCLUSIONS: The results
      presented suggest that catastrophisation, FAB and low self-efficacy could be
      potential barriers to early improvement during chiropractic care. In most
      patients presenting with higher psychological scores these were reduced within a
      few days of an initial chiropractic visit. Those patients who exhibited higher
      adverse psychology post-initial visit appear to have an increased risk of poor
      outcome at 1 month.

PMID- 20673331
TI  - Microbial oxidation of arsenite in a subarctic environment: diversity of arsenite
      oxidase genes and identification of a psychrotolerant arsenite oxidiser.
AB  - BACKGROUND: Arsenic is toxic to most living cells. The two soluble inorganic
      forms of arsenic are arsenite (+3) and arsenate (+5), with arsenite the more
      toxic. Prokaryotic metabolism of arsenic has been reported in both thermal and
      moderate environments and has been shown to be involved in the redox cycling of
      arsenic. No arsenic metabolism (either dissimilatory arsenate reduction or
      arsenite oxidation) has ever been reported in cold environments (i.e. < 10
      degrees C). RESULTS: Our study site is located 512 kilometres south of the Arctic
      Circle in the Northwest Territories, Canada in an inactive gold mine which
      contains mine waste water in excess of 50 mM arsenic. Several thousand tonnes of
      arsenic trioxide dust are stored in underground chambers and microbial biofilms
      grow on the chamber walls below seepage points rich in arsenite-containing
      solutions. We compared the arsenite oxidisers in two subsamples (which differed
      in arsenite concentration) collected from one biofilm. 'Species' (sequence)
      richness did not differ between subsamples, but the relative importance of the
      three identifiable clades did. An arsenite-oxidising bacterium (designated GM1)
      was isolated, and was shown to oxidise arsenite in the early exponential growth
      phase and to grow at a broad range of temperatures (4-25 degrees C). Its arsenite
      oxidase was constitutively expressed and functioned over a broad temperature
      range. CONCLUSIONS: The diversity of arsenite oxidisers does not significantly
      differ from two subsamples of a microbial biofilm that vary in arsenite
      concentrations. GM1 is the first psychrotolerant arsenite oxidiser to be isolated
      with the ability to grow below 10 degrees C. This ability to grow at low
      temperatures could be harnessed for arsenic bioremediation in moderate to cold
      climates.

PMID- 20673332
TI  - Cytosolic phospholipase A2 alpha amplifies early cyclooxygenase-2 expression,
      oxidative stress and MAP kinase phosphorylation after cerebral ischemia in mice.
AB  - BACKGROUND: The enzyme cytosolic phospholipase A2 alpha (cPLA2alpha) has been
      implicated in the progression of cerebral injury following ischemia and
      reperfusion. Previous studies in rodents suggest that cPLA2alpha enhances delayed
      injury extension and disruption of the blood brain barrier many hours after
      reperfusion. In this study we investigated the role of cPLA2alpha in early
      ischemic cerebral injury. METHODS: Middle cerebral artery occlusion (MCAO) was
      performed on cPLA2alpha+/+ and cPLA2alpha-/- mice for 2 hours followed by 0, 2,
      or 6 hours of reperfusion. The levels of cPLA2alpha, cyclooxygenase-2, neuronal
      morphology and reactive oxygen species in the ischemic and contralateral
      hemispheres were evaluated by light and fluorescent microscopy. PGE2 content was
      compared between genotypes and hemispheres after MCAO and MCAO and 6 hours
      reperfusion. Regional cerebral blood flow was measured during MCAO and
      phosphorylation of relevant MAPKs in brain protein homogenates was measured by
      Western analysis after 6 hours of reperfusion. RESULTS: Neuronal cPLA2alpha
      protein increased by 2-fold immediately after MCAO and returned to pre-MCAO
      levels after 2 hours reperfusion. Neuronal cyclooxygenase-2 induction and PGE2
      concentration were greater in cPLA2alpha+/+ compared to cPLA2alpha-/- ischemic
      cortex. Neuronal swelling in ischemic regions was significantly greater in the
      cPLA2alpha+/+ than in cPLA2alpha-/- brains (+/+:2.2+/-0.3 fold vs. -/-:1.7+/-0.4
      fold increase; P<0.01). The increase in reactive oxygen species following 2 hours
      of ischemia was also significantly greater in the cPLA2alpha+/+ ischemic core
      than in cPLA2alpha-/- (+/+:7.12+/-1.2 fold vs. -/-:3.1+/-1.4 fold; P<0.01). After
      6 hours of reperfusion ischemic cortex of cPLA2alpha+/+, but not cPLA2alpha-/-,
      had disruption of neuron morphology and decreased PGE2 content. Phosphorylation
      of the MAPKs-p38, ERK 1/2, and MEK 1/2-was significantly greater in cPLA2a+/+
      than in cPLA2alpha-/- ischemic cortex 6 hours after reperfusion. CONCLUSIONS:
      These results indicate that cPLA2alpha modulates the earliest molecular and
      injury responses after cerebral ischemia and have implications for the potential
      clinical use of cPLA2alpha inhibitors.

PMID- 20673333
TI  - NDRG2 suppresses the proliferation of clear cell renal cell carcinoma cell A-498.
AB  - BACKGROUND: Recently, the anti-tumor activity of N-myc downstream-regulated gene
      2 (NDRG2) was shown decreased expression in clear cell renal cell carcinoma
      (CCRCC), but the role of the down-expression of NDRG2 has not been described.
      METHODS: The NDRG2 recombinant adenovirus plasmid was constructed. The
      proliferation rate and NDRG2 expression of cell infected with recombinant plasmid
      were mesured by MTT, Flow cytometry analysis and western blot. RESULTS: The CCRCC
      cell A-498 re-expressed NDRG2 when infected by NDRG2 recombinant adenovirus and
      significantly decreased the proliferation rate. Fluorescence activated cell
      sorter analysis showed that 25.00% of cells expressed NDRG2 were in S-phase
      compared to 40.67% of control cells, whereas 62.08% of cells expressed NDRG2 were
      in G1-phase compared to 54.39% of control cells (P < 0.05). In addition, there
      were much more apoptotic cells in NDRG2-expressing cells than in the controls (P
      < 0.05). Moreover, upregulation of NDRG2 protein was associated with a reduction
      in cyclin D1, cyclin E, whereas cyclinD2, cyclinD3 and cdk2 were not affected
      examined by western blot. Furthermore, we found that p53 could upregulate NDRG2
      expression in A-498 cell. CONCLUSIONS: We found that NDRG2 can inhibit the
      proliferation of the renal carcinoma cells and induce arrest at G1 phase. p53 can
      up-regulate the expression of NDRG2. Our results showed that NDRG2 may function
      as a tumor suppressor in CCRCC.

PMID- 20673335
TI  - OpenChrom: a cross-platform open source software for the mass spectrometric
      analysis of chromatographic data.
AB  - BACKGROUND: Today, data evaluation has become a bottleneck in chromatographic
      science. Analytical instruments equipped with automated samplers yield large
      amounts of measurement data, which needs to be verified and analyzed. Since
      nearly every GC/MS instrument vendor offers its own data format and software
      tools, the consequences are problems with data exchange and a lack of
      comparability between the analytical results. To challenge this situation a
      number of either commercial or non-profit software applications have been
      developed. These applications provide functionalities to import and analyze
      several data formats but have shortcomings in terms of the transparency of the
      implemented analytical algorithms and/or are restricted to a specific computer
      platform. RESULTS: This work describes a native approach to handle
      chromatographic data files. The approach can be extended in its functionality
      such as facilities to detect baselines, to detect, integrate and identify peaks
      and to compare mass spectra, as well as the ability to internationalize the
      application. Additionally, filters can be applied on the chromatographic data to
      enhance its quality, for example to remove background and noise. Extended
      operations like do, undo and redo are supported. CONCLUSIONS: OpenChrom is a
      software application to edit and analyze mass spectrometric chromatographic data.
      It is extensible in many different ways, depending on the demands of the users or
      the analytical procedures and algorithms. It offers a customizable graphical user
      interface. The software is independent of the operating system, due to the fact
      that the Rich Client Platform is written in Java. OpenChrom is released under the
      Eclipse Public License 1.0 (EPL). There are no license constraints regarding
      extensions. They can be published using open source as well as proprietary
      licenses. OpenChrom is available free of charge at http://www.openchrom.net.

PMID- 20673334
TI  - A case-control analysis of common variants in GIP with type 2 diabetes and
      related biochemical parameters in a South Indian population.
AB  - BACKGROUND: Glucose-dependent insulinotropic polypeptide (GIP) is one of the
      incretins, which plays a crucial role in the secretion of insulin upon food
      stimulus and in the regulation of postprandial glucose level. It also exerts an
      effect on the synthesis and secretion of lipoprotein lipase, from adipocytes,
      important for lipid metabolism. The aim of our study was to do a case-control
      association analysis of common variants in GIP in association with type 2
      diabetes and related biochemical parameters. METHOD: A total of 2000 subjects
      which includes 1000 (584M/416F) cases with type 2 diabetes and 1000 (470M/530F)
      normoglycemic control subjects belonging to Dravidian ethnicity from South India
      were recruited to assess the effect of single nucleotide polymorphisms (SNPs) in
      GIP (rs2291725, rs2291726, rs937301) on type 2 diabetes in a case-control manner.
      The SNPs were genotyped by using tetra primer amplification refractory mutation
      system-PCR (ARMS PCR). For statistical analysis, our study population was divided
      into sub-groups based on gender (male and female). Association analysis was
      carried out using chi-squared test and the comparison of biochemical parameters
      among the three genotypes were performed using analysis of covariance (ANCOVA).
      RESULT: Initial analysis revealed that, out of the total three SNPs selected for
      the present study, two SNPs namely rs2291726 and rs937301 were in complete
      linkage disequilibrium (LD) with each other. Therefore, only two SNPs, rs2291725
      and rs2291726, were genotyped for the association studies. No significant
      difference in the allele frequency and genotype distribution of any of the SNPs
      in GIP were observed between cases and controls (P > 0.05). Analysis of
      biochemical parameters among the three genotypes showed a significant association
      of total cholesterol (P = 0.042) and low density lipoprotein (LDL) with the G
      allele of the SNP rs2291726 in GIP (P = 0.004), but this was observed only in the
      case of female subjects. However this association does not remain significant
      after correction for multiple testing by Bonferroni's inequality method.
      CONCLUSION: No statistically significant association was observed between any of
      the SNPs analysed and type 2 diabetes in our population. But the analysis of
      biochemical parameters indicates that the G allele in rs2291726 may be a putative
      risk allele for increased LDL cholesterol and further studies in other population
      needs to be carried out for ascertaining its role in cholesterol metabolism and
      subsequent cardiovascular risk.

PMID- 20673337
TI  - Predictive factors of non-deterioration of glucose tolerance following a 2-year
      behavioral intervention.
AB  - AIM: To identify predictive factors associated with non-deterioration of glucose
      metabolism following a 2-year behavioral intervention in Japanese-Brazilians.
      METHODS: 295 adults (59.7% women) without diabetes completed 2-year intervention
      program. Characteristics of those who maintained/improved glucose tolerance
      status (non-progressors) were compared with those who worsened (progressors)
      after the intervention. In logistic regression analysis, the condition of non
      progressor was used as dependent variable. RESULTS: Baseline characteristics of
      non-progressors (71.7%) and progressors were similar, except for the former being
      younger and having higher frequency of disturbed glucose tolerance and lower C
      reactive protein (CRP). In logistic regression, non-deterioration of glucose
      metabolism was associated with disturbed glucose tolerance - impaired fasting
      glucose or impaired glucose tolerance - (p < 0.001) and CRP levels </= 0.04 mg/dL
      (p = 0.01), adjusted for age and anthropometric variables. Changes in
      anthropometry and physical activity and achievement of weight and dietary goals
      after intervention were similar in subsets that worsened or not the glucose
      tolerance status. CONCLUSION: The whole sample presented a homogeneous behavior
      during the intervention. Lower CRP levels and diagnosis of glucose intolerance at
      baseline were predictors of non-deterioration of the glucose metabolism after a
      relatively simple intervention, independent of body adiposity.

PMID- 20673336
TI  - Taxonomic distribution and origins of the extended LHC (light-harvesting complex)
      antenna protein superfamily.
AB  - BACKGROUND: The extended light-harvesting complex (LHC) protein superfamily is a
      centerpiece of eukaryotic photosynthesis, comprising the LHC family and several
      families involved in photoprotection, like the LHC-like and the photosystem II
      subunit S (PSBS). The evolution of this complex superfamily has long remained
      elusive, partially due to previously missing families. RESULTS: In this study we
      present a meticulous search for LHC-like sequences in public genome and expressed
      sequence tag databases covering twelve representative photosynthetic eukaryotes
      from the three primary lineages of plants (Plantae): glaucophytes, red algae and
      green plants (Viridiplantae). By introducing a coherent classification of the
      different protein families based on both, hidden Markov model analyses and
      structural predictions, numerous new LHC-like sequences were identified and
      several new families were described, including the red lineage chlorophyll a/b
      binding-like protein (RedCAP) family from red algae and diatoms. The test of
      alternative topologies of sequences of the highly conserved chlorophyll-binding
      core structure of LHC and PSBS proteins significantly supports the independent
      origins of LHC and PSBS families via two unrelated internal gene duplication
      events. This result was confirmed by the application of cluster likelihood
      mapping. CONCLUSIONS: The independent evolution of LHC and PSBS families is
      supported by strong phylogenetic evidence. In addition, a possible origin of LHC
      and PSBS families from different homologous members of the stress-enhanced
      protein subfamily, a diverse and anciently paralogous group of two-helix
      proteins, seems likely. The new hypothesis for the evolution of the extended LHC
      protein superfamily proposed here is in agreement with the character evolution
      analysis that incorporates the distribution of families and subfamilies across
      taxonomic lineages. Intriguingly, stress-enhanced proteins, which are universally
      found in the genomes of green plants, red algae, glaucophytes and in diatoms with
      complex plastids, could represent an important and previously missing link in the
      evolution of the extended LHC protein superfamily.

PMID- 20673338
TI  - The Drosophila homolog of the mammalian imprint regulator, CTCF, maintains the
      maternal genomic imprint in Drosophila melanogaster.
AB  - BACKGROUND: CTCF is a versatile zinc finger DNA-binding protein that functions as
      a highly conserved epigenetic transcriptional regulator. CTCF is known to act as
      a chromosomal insulator, bind promoter regions, and facilitate long-range
      chromatin interactions. In mammals, CTCF is active in the regulatory regions of
      some genes that exhibit genomic imprinting, acting as insulator on only one
      parental allele to facilitate parent-specific expression. In Drosophila, CTCF
      acts as a chromatin insulator and is thought to be actively involved in the
      global organization of the genome. RESULTS: To determine whether CTCF regulates
      imprinting in Drosophila, we generated CTCF mutant alleles and assayed gene
      expression from the imprinted Dp(1;f)LJ9 mini-X chromosome in the presence of
      reduced CTCF expression. We observed disruption of the maternal imprint when CTCF
      levels were reduced, but no effect was observed on the paternal imprint. The
      effect was restricted to maintenance of the imprint and was specific for the
      Dp(1;f)LJ9 mini-X chromosome. CONCLUSIONS: CTCF in Drosophila functions in
      maintaining parent-specific expression from an imprinted domain as it does in
      mammals. We propose that Drosophila CTCF maintains an insulator boundary on the
      maternal X chromosome, shielding genes from the imprint-induced silencing that
      occurs on the paternally inherited X chromosome. See commentary:
      http://www.biomedcentral.com/1741-7007/8/104.

PMID- 20673339
TI  - Control of positive end-expiratory pressure (PEEP) for small animal ventilators.
AB  - BACKGROUND: The positive end-expiratory pressure (PEEP) for the mechanical
      ventilation of small animals is frequently obtained with water seals or by using
      ventilators developed for human use. An alternative mechanism is the use of an on
      off expiratory valve closing at the moment when the alveolar pressure is equal to
      the target PEEP. In this paper, a novel PEEP controller (PEEP-new) and the PEEP
      system of a commercial small-animal ventilator, both based on switching an on-off
      valve, are evaluated. METHODS: The proposed PEEP controller is a discrete
      integrator monitoring the error between the target PEEP and the airways opening
      pressure prior to the onset of an inspiratory cycle. In vitro as well as in vivo
      experiments with rats were carried out and the PEEP accuracy, settling time and
      under/overshoot were considered as a measure of performance. RESULTS: The
      commercial PEEP controller did not pass the tests since it ignores the airways
      resistive pressure drop, resulting in a PEEP 5 cmH2O greater than the target in
      most conditions. The PEEP-new presented steady-state errors smaller than 0.5
      cmH2O, with settling times below 10 s and under/overshoot smaller than 2 cmH2O.
      CONCLUSION: The PEEP-new presented acceptable performance, considering accuracy
      and temporal response. This novel PEEP generator may prove useful in many
      applications for small animal ventilators.

PMID- 20673340
TI  - CT-guided iodine-125 seed permanent implantation for recurrent head and neck
      cancers.
AB  - BACKGROUND: To investigate the feasibility, and safety of 125I seed permanent
      implantation for recurrent head and neck carcinoma under CT-guidance. RESULTS: A
      retrospective study on 14 patients with recurrent head and neck cancers undergone
      125I seed implantation with different seed activities. The post-plan showed that
      the actuarial D90 of 125I seeds ranged from 90 to 218 Gy (median, 157.5 Gy). The
      follow-up was 3 to 60 months (median, 13 months). The median local control was 18
      months (95% CI, 6.1-29.9 months), and the 1-, 2-, 3-, and 5- year local controls
      were 52%, 39%, 39%, and 39%, respectively. The 1-, 2-, 3-, and 5- survival rates
      were 65%, 39%, 39% and 39%, respectively, with a median survival time of 20
      months (95% CI, 8.7-31.3 months). Of all patients, 28.6% (4/14) died of local
      recurrence, 7.1% (1/14) died of metastases, one patient died of hepatocirrhosis,
      and 8 patients are still alive to the date of data analysis. CONCLUSION: CT
      guided 125I seed implantation is feasible and safe as a salvage or palliative
      treatment for patients with recurrent head and neck cancers.

PMID- 20673341
TI  - Effects of cerebrovascular disease on amyloid precursor protein metabolites in
      cerebrospinal fluid.
AB  - BACKGROUND: Alzheimer's disease (AD) and cerebrovascular disease (CVD) including
      chronic small vessel disease of the brain (SVD) are the most frequent causes of
      dementia. AD is associated with metabolism of amyloid precursor protein (APP) and
      low levels of amyloid-beta peptide (Abeta) X-42 in the cerebrospinal fluid (CSF).
      CVD and SVD are established risk factors for AD, brain white matter lesions (WML)
      are established surrogate markers for SVD and are also associated with reduced
      CSF AbetaX-42.A cohort survey was performed to examine whether SVD or acute CVD
      affects APP metabolism and to explore a potential association between WML and APP
      metabolism in two groups; cognitively impaired patients, subjective and mild (SCI
      and MCI) and stroke patients. Through measurements of CSF APP metabolite levels
      in patients with a wide range of WML volumes, this study aimed to determine how
      SVD influences APP metabolism. METHODS: Sixty-three patients were included: 37
      with subjective cognitive impairment (SCI) or mild cognitive impairment (MCI)
      without stroke, and 26 after acute stroke. Chronic and acute WML volume and
      infarct volume were determined by magnetic resonance imaging (MRI) post-scan
      processing, and CSF levels of alpha- and beta-cleaved soluble APP (sAPP-alpha and
      sAPP-beta, AbetaX-38, AbetaX-40 and AbetaX-42) were determined. The Mann-Whitney
      test was used to compare the patient groups. Chronic and acute WML volumes,
      infarct volume, age, and sex were used as predictors for CSF biomarker levels in
      linear regression analysis. RESULTS: CSF levels of sAPP-alpha and sAPP-beta were
      strongly correlated (r = 0.95, p < 0.001) and lower levels of these biomarkers
      were found in the stroke group than in the SCI/MCI group; median sAPP-alpha 499.5
      vs. 698.0 ng/mL (p < 0.001), sAPP-beta 258.0 vs. 329.0 ng/mL (p < 0.005). CSF
      levels of sAPP-alpha, sAPP-beta, AbetaX-38, AbetaX-40 and AbetaX-42 were
      inversely correlated with chronic WML volume (p </= 0.005; p </= 0.01; p </=
      0.01; p </= 0.05; p </= 0.05 respectively), but not with acute WML or infarct
      volumes. CONCLUSIONS: Lower CSF levels of sAPP-alpha and sAPP-beta in the stroke
      group than in the SCI/MCI group and an inverse correlation with chronic WML
      indicate that ischemia lowers the levels of CSF sAPP metabolites and suggests
      that APP axonal transport or metabolism may be affected in SVD of the brain.

PMID- 20673342
TI  - What's the effect of the implementation of general practitioner cooperatives on
      caseload? Prospective intervention study on primary and secondary care.
AB  - BACKGROUND: Out-of-hours care in the primary care setting is rapidly changing and
      evolving towards general practitioner 'cooperatives' (GPC). GPCs already exist in
      the Netherlands, the United Kingdom and Scandinavia, all countries with strong
      general practice, including gatekeepers' role. This intervention study reports
      the use and caseload of out-of-hours care before and after implementation of a
      GPC in a well subscribed region in a country with an open access health care
      system and no gatekeepers' role for general practice. METHODS: We used a
      prospective before/after interventional study design. The intervention was the
      implementation of a GPC. RESULTS: One year after the implementation of a GPC, the
      number of patient contacts in the intervention region significantly increased at
      the GPC (OR: 1.645; 95% CI: 1.439-1.880), while there were no significant changes
      in patient contacts at the Emergency Department (ED) or in other regions where a
      simultaneous registration was performed. Although home visits decreased in all
      general practitioner registrations, the difference was more pronounced in the
      intervention region (intervention region: OR: 0.515; 95% CI: 0.411-0.646, other
      regions: OR: 0.743; 95% CI: 0.608-0.908). At the ED we observed a decrease in the
      number of trauma cases (OR: 0.789; 95% CI: 0.648-0.960) and of patients who came
      to hospital by ambulance (OR: 0.687; 95% CI: 0.565-0.836). CONCLUSIONS: One year
      after its implementation more people seek help at the GPC, while the number of
      contacts at the ED remains the same. The most prominent changes in caseload are
      found in the trauma cases. Establishing a GPC in an open health care system,
      might redirect some patients with particular medical problems to primary care.
      This could lead to a lowering of costs or a more cost-effective out of hours
      care, but further research should focus on effective usage to divert patient
      flows and on quality and outcome of care.

PMID- 20673343
TI  - Ethics review as a component of institutional approval for a multicentre
      continuous quality improvement project: the investigator's perspective.
AB  - BACKGROUND: For ethical approval of a multicentre study in Canada, investigators
      must apply separately to individual Research Ethics Boards (REBs). In principle,
      the protection of human research subjects is of utmost importance. However, in
      practice, the process of multicentre ethics review can be time consuming and
      costly, requiring duplication of effort for researchers and REBs. We used our
      experience with ethical review of The Canadian Perinatal Network (CPN), to gain
      insight into the Canadian system. METHODS: The applications forms of 16 different
      REBs were abstracted for a list of standardized items. The application process
      across sites was compared. Correspondence between the REB and the investigators
      was documented in order to construct a timeline to approval, identify the
      specific issues raised by each board, and describe how they were resolved.
      RESULTS: Each REB had a different application form. Most (n = 9) had a two or
      three step application process. Overall, it took a median of 31 days (range 2-174
      days) to receive an initial response from the REB. Approval took a median of 42
      days (range 4-443 days). Privacy and consent were the two major issues raised.
      Several additional minor or administrative issues were raised which delayed
      approval. CONCLUSIONS: For CPN, the Canadian REB process of ethical review proved
      challenging. REBs acted independently and without unified application forms or
      submission procedures. We call for a critical examination of the ethical, privacy
      and institutional review processes in Canada, to determine the best way to
      undertake multicentre review.

PMID- 20673344
TI  - Acute Unstable Depressive Syndrome (AUDS) is associated more frequently with
      epilepsy than major depression.
AB  - BACKGROUND: Depressive disorders are frequent in epilepsy and associated with
      reduced seizure control. Almost 50% of interictal depressive disorders have to be
      classified as atypical depressions according to DSM-4 criteria. Research has
      mainly focused on depressive symptoms in defined populations with epilepsy (e.g.,
      patients admitted to tertiary epilepsy centers). We have chosen the opposite
      approach. We hypothesized that it is possible to define by clinical means a
      subgroup of psychiatric patients with higher than expected prevalence of epilepsy
      and seizures. We hypothesized further that these patients present with an Acute
      Unstable Depressive Syndrome (AUDS) that does not meet DSM-IV criteria of a Major
      Depressive Episode (MDE). In a previous publication we have documented that AUDS
      patients indeed have more often a history of epileptic seizures and abnormal EEG
      recordings than MDE patients (Vaaler et al. 2009). This study aimed to further
      classify the differences of depressive symptoms at admittance and follow-up of
      patients with AUDS and MDE. METHODS: 16 AUDS patients and 16 age- and sex-matched
      MDE patients were assessed using the Symptomatic Organic Mental Disorder
      Assessment Scale (SOMAS), the Montgomery and Asberg Depression Rating Scale
      (MADRS), and the Mini-Mental State Test (MMST), at day 2, day 4-6, day 14-16 and
      3 months after admittance to a psychiatric emergency unit. Life events were
      assessed with The Social Readjustment Rating Scale (SRRS) and The Life Experience
      Survey (LES). We also screened for medication serum levels and illicit drug
      metabolites in urine. RESULTS: AUDS patients had significantly higher SOMAS
      scores (average score at admission 6.6 +/- 0.8), reflecting increased symptom
      fluctuation and motor agitation, and decreased insight and concern compared to
      MDE patients (2.9 +/- 0.7; p < 0.001). Degree of mood depression, cognition, life
      events, drug abuse and medication did not differ between the two groups.
      CONCLUSIONS: AUDS patients present with rapidly fluctuating mood symptoms, motor
      agitation and relative lack of insight and concern. Seizures, epilepsy and EEG
      abnormalities are overrepresented in AUDS patients compared to MDE patients. We
      suggest that the study of AUDS patients may offer a new approach to better
      understanding epilepsy and its association with depressive disorders. TRIAL
      REGISTRATION: NCT00201474.

PMID- 20673345
TI  - Tracking tumor evolution via prostate-specific antigen: an individual post
      operative study.
AB  - BACKGROUND: The progress of the prostate-specific antigen (PSA) level after
      radical prostatectomy is observed for a patient in order to extract information
      about the mode of tumor cell growth. Although PSA values are determined routinely
      to find the doubling time of the prostate marker, to our knowledge, this analysis
      is the first in the literature. RESULTS: The prostate tumor marker values were
      determined regularly after the surgery and plotted on a logarithmic scale against
      time. An initial rapid-growth mode changed to a slower power-law regime within
      two years of surgery. Our analysis associates this observation with a transition
      in the growth mode from unrestricted growth of dispersed cells to their clumping
      into macroscopic structures. CONCLUSIONS: Such studies may help determine the
      appropriate time window for postoperative therapies in order to increase the life
      expectancy of the patient.

PMID- 20673346
TI  - A case report of thoracic compartment syndrome in the setting of penetrating
      chest trauma and review of the literature.
AB  - Trauma-related thoracic compartment syndrome (TCS) is a rare, life threatening
      condition that develops secondary to elevated intra-thoracic pressure and
      manifests itself clinically as significantly elevated airway pressures, inability
      to provide adequate ventilation and hemodynamic instability temporally related to
      closure of a thoracic surgical incision. TCS is exceedingly rare in the trauma
      population. We present a case of TCS following surgical repair of a stab wound
      injury that necessitated decompressive thoracotomy and peri-operative open-chest
      management.

PMID- 20673347
TI  - The effect of different cardiovascular risk presentation formats on intentions,
      understanding and emotional affect: a randomised controlled trial using a web
      based risk formatter (protocol).
AB  - BACKGROUND: The future risk of heart disease can be predicted with increasing
      precision. However, more research is needed into how this risk is conveyed and
      presented. The aim of this study is to compare the effects of presenting
      cardiovascular risk in different formats on individuals' intention to change
      behaviour to reduce risk, understanding of risk information and emotional affect.
      METHODS/DESIGN: A randomised controlled trial comprising four arms, with a
      between subjects design will be performed. There will be two intervention groups
      and two control groups. The first control comprises a pre-intervention
      questionnaire and presents risk in a bar graph format. The second control
      presents risk in a bar graph format without pre-intervention questionnaire. These
      two control groups are to account for the potential Hawthorne effect of thinking
      about cardiovascular risk before viewing actual risk. The two intervention groups
      comprise presenting risk in either a pictogram or metonym format (image depicting
      seriousness of having a myocardial infarction). 800 individuals' aged between 45
      and 64 years, who have not been previously diagnosed with heart disease and have
      access to a computer with internet, will be given a link to a website comprising
      a risk calculator and electronic questionnaires. 10-year risk of having a
      coronary heart disease event will be assessed and presented in one of the three
      formats. A post-intervention questionnaire will be completed after viewing the
      risk format. Main outcome measures are (i) intention to change behaviour, (ii)
      understanding of risk information, (iii) emotional affect and (iv) worry about
      future heart disease. Secondary outcomes are the sub-components of the theory of
      planned behaviour: attitudes, perceived behavioural control and subjective norms.
      DISCUSSION: Having reviewed the literature, we are not aware of any other studies
      which have used the assessment of actual risk, in a trial to compare different
      graphical cardiovascular risk presentation formats. This trial will provide data
      about which graphical cardiovascular risk presentation format is most effective
      in encouraging behaviour change to reduce cardiovascular risk. TRIAL
      REGISTRATION: Current Controlled Trials ISRCTN91319318.

PMID- 20673349
TI  - The enigmatic nature of altruism in organ transplantation: a cross-cultural study
      of transplant physicians' views on altruism.
AB  - BACKGROUND: Although altruism is a key principle in our current organ donation
      and transplantation system, the meanings and implications of the term have been
      widely debated. Recently, a new type of living organ donation--anonymous and non
      directed, also called living altruistic donation (LAD)--has brought the issue
      into sharper focus. Transplant physicians' views on altruism might influence
      their attitudes and actions toward living altruistic donors. This study aimed to
      explore such views among transplant physicians in France and Quebec. FINDINGS: A
      total of 27 French and 19 Quebec transplant physicians participated in
      individual, semi-structured interviews between October 2004 and December 2005.
      The majority of these participants associated altruism with gratuitousness and
      saw altruistic acts as multiple and varied, ranging from showing consideration to
      saving a person's life. CONCLUSIONS: The transplant physicians' discourses on
      altruism were quite diverse, leading us to question the relevance of the concept
      in organ transplantation and the appropriateness of the term "living altruistic
      donation."

PMID- 20673348
TI  - GU81, a VEGFR2 antagonist peptoid, enhances the anti-tumor activity of
      doxorubicin in the murine MMTV-PyMT transgenic model of breast cancer.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) is a primary stimulant of
      angiogenesis under physiological and pathological conditions. Anti-VEGF therapy
      is a clinically proven strategy for the treatment of a variety of cancers
      including colon, breast, lung, and renal cell carcinoma. Since VEGFR2 is the
      dominant angiogenic signaling receptor, it has become an important target in the
      development of novel anti-angiogenic therapies. We have reported previously the
      development of an antagonistic VEGFR2 peptoid (GU40C4) that has promising anti
      angiogenic activity in vitro and in vivo. METHODS: In the current study, we
      utilize a derivative of GU40C4, termed GU81 in therapy studies. GU81 was tested
      alone or in combination with doxorubicin for in vivo efficacy in the MMTV-PyMT
      transgenic model of breast cancer. RESULTS: The derivative GU81 has increased in
      vitro efficacy compared to GU40C4. Single agent therapy (doxorubicin or GU81
      alone) had no effect on tumor weight, histology, tumor fat content, or tumor
      growth index. However, GU81 is able to significantly to reduce total vascular
      area as a single agent. GU81 used in combination with doxorubicin significantly
      reduced tumor weight and growth index compared to all other treatment groups.
      Furthermore, treatment with combination therapy significantly arrested tumor
      progression at the premalignant stage, resulting in increased tumor fat content.
      Interestingly, treatment with GU81 alone increased tumor-VEGF levels and
      macrophage infiltration, an effect that was abrogated when used in combination
      with doxorubicin. CONCLUSION: This study demonstrates the VEGFR2 antagonist
      peptoid, GU81, enhances the anti-tumor activity of doxorubicin in spontaneous
      murine MMTV-PyMT breast tumors.

PMID- 20673350
TI  - An open-source software tool for the generation of relaxation time maps in
      magnetic resonance imaging.
AB  - BACKGROUND: In magnetic resonance (MR) imaging, T1, T2 and T2* relaxation times
      represent characteristic tissue properties that can be quantified with the help
      of specific imaging strategies. While there are basic software tools for specific
      pulse sequences, until now there is no universal software program available to
      automate pixel-wise mapping of relaxation times from various types of images or
      MR systems. Such a software program would allow researchers to test and compare
      new imaging strategies and thus would significantly facilitate research in the
      area of quantitative tissue characterization. RESULTS: After defining
      requirements for a universal MR mapping tool, a software program named MRmap was
      created using a high-level graphics language. Additional features include a
      manual registration tool for source images with motion artifacts and a tabular
      DICOM viewer to examine pulse sequence parameters. MRmap was successfully tested
      on three different computer platforms with image data from three different MR
      system manufacturers and five different sorts of pulse sequences: multi-image
      inversion recovery T1; Look-Locker/TOMROP T1; modified Look-Locker (MOLLI) T1;
      single-echo T2/T2*; and multi-echo T2/T2*. Computing times varied between 2 and
      113 seconds. Estimates of relaxation times compared favorably to those obtained
      from non-automated curve fitting. Completed maps were exported in DICOM format
      and could be read in standard software packages used for analysis of clinical and
      research MR data. CONCLUSIONS: MRmap is a flexible cross-platform research tool
      that enables accurate mapping of relaxation times from various pulse sequences.
      The software allows researchers to optimize quantitative MR strategies in a
      manufacturer-independent fashion. The program and its source code were made
      available as open-source software on the internet.

PMID- 20673351
TI  - Some considerations for analyzing biodiversity using integrative metagenomics and
      gene networks.
AB  - BACKGROUND: Improving knowledge of biodiversity will benefit conservation
      biology, enhance bioremediation studies, and could lead to new medical
      treatments. However there is no standard approach to estimate and to compare the
      diversity of different environments, or to study its past, and possibly, future
      evolution. PRESENTATION OF THE HYPOTHESIS: We argue that there are two conditions
      for significant progress in the identification and quantification of
      biodiversity. First, integrative metagenomic studies - aiming at the simultaneous
      examination (or even better at the integration) of observations about the
      elements, functions and evolutionary processes captured by the massive sequencing
      of multiple markers - should be preferred over DNA barcoding projects and over
      metagenomic projects based on a single marker. Second, such metagenomic data
      should be studied with novel inclusive network-based approaches, designed to draw
      inferences both on the many units and on the many processes present in the
      environments. TESTING THE HYPOTHESIS: We reached these conclusions through a
      comparison of the theoretical foundations of two molecular approaches seeking to
      assess biodiversity: metagenomics (mostly used on prokaryotes and protists) and
      DNA barcoding (mostly used on multicellular eukaryotes), and by pragmatic
      considerations of the issues caused by the 'species problem' in biodiversity
      studies. IMPLICATIONS OF THE HYPOTHESIS: Evolutionary gene networks reduce the
      risk of producing biodiversity estimates with limited explanatory power, biased
      either by unequal rates of LGT, or difficult to interpret due to (practical)
      problems caused by type I and type II grey zones. Moreover, these networks would
      easily accommodate additional (meta)transcriptomic and (meta)proteomic data.

PMID- 20673352
TI  - Simvastatin attenuates ventilator-induced lung injury in mice.
AB  - INTRODUCTION: Mechanical ventilation (MV) is a life saving intervention in acute
      respiratory failure without alternative. However, particularly in pre-injured
      lungs, even protective ventilation strategies may evoke ventilator-induced lung
      injury (VILI), which is characterized by pulmonary inflammation and vascular
      leakage. Adjuvant pharmacologic strategies in addition to lung protective
      ventilation to attenuate VILI are lacking. Simvastatin exhibited anti
      inflammatory and endothelial barrier stabilizing properties in vitro and in vivo.
      METHODS: Mice were ventilated (12 ml/kg; six hours) and subjected to simvastatin
      (20 mg/kg) or sham treatment. Pulmonary microvascular leakage, oxygenation,
      pulmonary and systemic neutrophil and monocyte counts and cytokine release in
      lung and blood plasma were assessed. Further, lung tissue was analyzed by
      electron microscopy. RESULTS: Mechanical ventilation induced VILI, displayed by
      increased pulmonary microvascular leakage and endothelial injury, pulmonary
      recruitment of neutrophils and Gr-1high monocytes, and by liberation of
      inflammatory cytokines in the lungs. Further, VILI associated systemic
      inflammation characterized by blood leukocytosis and elevated plasma cytokines
      was observed. Simvastatin treatment limited pulmonary endothelial injury,
      attenuated pulmonary hyperpermeability, prevented the recruitment of leukocytes
      to the lung, reduced pulmonary cytokine levels and improved oxygenation in
      mechanically ventilated mice. CONCLUSIONS: High-dose simvastatin attenuated VILI
      in mice by reducing MV-induced pulmonary inflammation and hyperpermeability.

PMID- 20673353
TI  - Adjuvant radiotherapy and chemotherapy in breast cancer: 30 year follow-up of
      survival.
AB  - BACKGROUND: The long term outcome (more than 15 years) of adjuvant treatment in
      patients with primary operable breast cancer has rarely been examined. METHODS: A
      randomised clinical trial of radiotherapy, chemotherapy (28 day cycles of
      cyclophosphamide, methotrexate and 5-fluorouracil) or both on women with primary
      operable breast cancer (n = 322) was followed-up for a median of 27 years.
      RESULTS: 260 (81%) patients died, 204 (78%) from breast cancer. Cancer specific
      survival (SE) at 10 years, 20 years and 30 years was 41 (3)%, 34 (3)% and 33 (3)%
      respectively. Presence of more than 3 involved lymph nodes increased cancer
      specific mortality (HR 1.88, 95% CI 1.34-2.63) after adjustment for age, socio
      economic deprivation and adjuvant treatment. Both age (HR 1.63, 95% CI 1.19-2.22)
      and involved lymph nodes (HR 1.59, 95% CI 1.17-2.14) were significant predictors
      of all-cause mortality after adjustment for other factors. There was no
      significant difference in all-cause or cancer-specific survival between patients
      in each of the 3 treatment arms. CONCLUSIONS: The present study highlights the
      long term impact of node positive disease but does not indicate that any regimen
      was associated with significantly better long-term survival.

PMID- 20673354
TI  - Increased entropy of signal transduction in the cancer metastasis phenotype.
AB  - BACKGROUND: The statistical study of biological networks has led to important
      novel biological insights, such as the presence of hubs and hierarchical
      modularity. There is also a growing interest in studying the statistical
      properties of networks in the context of cancer genomics. However, relatively
      little is known as to what network features differ between the cancer and normal
      cell physiologies, or between different cancer cell phenotypes. RESULTS: Based on
      the observation that frequent genomic alterations underlie a more aggressive
      cancer phenotype, we asked if such an effect could be detectable as an increase
      in the randomness of local gene expression patterns. Using a breast cancer gene
      expression data set and a model network of protein interactions we derive
      constrained weighted networks defined by a stochastic information flux matrix
      reflecting expression correlations between interacting proteins. Based on this
      stochastic matrix we propose and compute an entropy measure that quantifies the
      degree of randomness in the local pattern of information flux around single
      genes. By comparing the local entropies in the non-metastatic versus metastatic
      breast cancer networks, we here show that breast cancers that metastasize are
      characterised by a small yet significant increase in the degree of randomness of
      local expression patterns. We validate this result in three additional breast
      cancer expression data sets and demonstrate that local entropy better
      characterises the metastatic phenotype than other non-entropy based measures. We
      show that increases in entropy can be used to identify genes and signalling
      pathways implicated in breast cancer metastasis and provide examples of de-novo
      discoveries of gene modules with known roles in apoptosis, immune-mediated tumour
      suppression, cell-cycle and tumour invasion. Importantly, we also identify a
      novel gene module within the insulin growth factor signalling pathway, alteration
      of which may predispose the tumour to metastasize. CONCLUSIONS: These results
      demonstrate that a metastatic cancer phenotype is characterised by an increase in
      the randomness of the local information flux patterns. Measures of local
      randomness in integrated protein interaction mRNA expression networks may
      therefore be useful for identifying genes and signalling pathways disrupted in
      one phenotype relative to another. Further exploration of the statistical
      properties of such integrated cancer expression and protein interaction networks
      will be a fruitful endeavour.

PMID- 20673355
TI  - Secular trends in pediatric antiretroviral treatment programs in rural and urban
      Zambia: a retrospective cohort study.
AB  - BACKGROUND: Since 2003 pediatric antiretroviral treatment (ART) programs have
      scaled-up in sub-Saharan Africa and should be evaluated to assess progress and
      identify areas for improvement. We evaluated secular trends in the
      characteristics and treatment outcomes of children in three pediatric ART clinics
      in urban and rural areas in Zambia. METHODS: Routinely collected data were
      analyzed from three ART programs in rural (Macha and Mukinge) and urban (Lusaka)
      Zambia between program implementation and July 2008. Data were obtained from
      electronic medical record systems and medical record abstraction, and were
      categorized by year of program implementation. Characteristics of all HIV
      infected and exposed children enrolled in the programs and all children
      initiating treatment were compared by year of implementation. RESULTS: Age
      decreased and immunologic characteristics improved in all groups over time in
      both urban and rural clinics, with greater improvement observed in the rural
      clinics. Among children both eligible and ineligible for ART at clinic
      enrollment, the majority started treatment within a year. A high proportion of
      children, particularly those ineligible for ART at clinic enrollment, were lost
      to follow-up prior to initiating ART. Among children initiating ART, clinical and
      immunologic outcomes after six months of treatment improved in both urban and
      rural clinics. In the urban clinics, mortality after six months of treatment
      declined with program duration, and in the rural clinics, the proportion of
      children defaulting by six months increased with program duration. CONCLUSIONS:
      Treatment programs are showing signs of progress in the care of HIV-infected
      children, particularly in the rural clinics where scale-up increased rapidly over
      the first three years of program implementation. However, continued efforts to
      optimize care are needed as many children continue to enroll in ART programs at a
      late stage of disease and thus are not receiving the full benefits of treatment.

PMID- 20673356
TI  - MS4--Multi-Scale Selector of Sequence Signatures: an alignment-free method for
      classification of biological sequences.
AB  - BACKGROUND: While multiple alignment is the first step of usual classification
      schemes for biological sequences, alignment-free methods are being increasingly
      used as alternatives when multiple alignments fail. Subword-based combinatorial
      methods are popular for their low algorithmic complexity (suffix trees ...) or
      exhaustivity (motif search), in general with fixed length word and/or number of
      mismatches. We developed previously a method to detect local similarities (the N
      local decoding) based on the occurrences of repeated subwords of fixed length,
      which does not impose a fixed number of mismatches. The resulting similarities
      are, for some "good" values of N, sufficiently relevant to form the basis of a
      reliable alignment-free classification. The aim of this paper is to develop a
      method that uses the similarities detected by N-local decoding while not imposing
      a fixed value of N. We present a procedure that selects for every position in the
      sequences an adaptive value of N, and we implement it as the MS4 classification
      tool. RESULTS: Among the equivalence classes produced by the N-local decodings
      for all N, we select a (relatively) small number of "relevant" classes
      corresponding to variable length subwords that carry enough information to
      perform the classification. The parameter N, for which correct values are data
      dependent and thus hard to guess, is here replaced by the average repetitivity
      kappa of the sequences. We show that our approach yields classifications of
      several sets of HIV/SIV sequences that agree with the accepted taxonomy, even on
      usually discarded repetitive regions (like the non-coding part of LTR).
      CONCLUSIONS: The method MS4 satisfactorily classifies a set of sequences that are
      notoriously hard to align. This suggests that our approach forms the basis of a
      reliable alignment-free classification tool. The only parameter kappa of MS4
      seems to give reasonable results even for its default value, which can be a great
      advantage for sequence sets for which little information is available.

PMID- 20673357
TI  - Atypical perceptual narrowing in prematurely born infants is associated with
      compromised language acquisition at 2 years of age.
AB  - BACKGROUND: Early auditory experiences are a prerequisite for speech and language
      acquisition. In healthy children, phoneme discrimination abilities improve for
      native and degrade for unfamiliar, socially irrelevant phoneme contrasts between
      6 and 12 months of age as the brain tunes itself to, and specializes in the
      native spoken language. This process is known as perceptual narrowing, and has
      been found to predict normal native language acquisition. Prematurely born
      infants are known to be at an elevated risk for later language problems, but it
      remains unclear whether these problems relate to early perceptual narrowing. To
      address this question, we investigated early neurophysiological phoneme
      discrimination abilities and later language skills in prematurely born infants
      and in healthy, full-term infants. RESULTS: Our follow-up study shows for the
      first time that perceptual narrowing for non-native phoneme contrasts found in
      the healthy controls at 12 months was not observed in very prematurely born
      infants. An electric mismatch response of the brain indicated that whereas full
      term infants gradually lost their ability to discriminate non-native phonemes
      from 6 to 12 months of age, prematurely born infants kept on this ability.
      Language performance tested at the age of 2 years showed a significant delay in
      the prematurely born group. Moreover, those infants who did not become
      specialized in native phonemes at the age of one year, performed worse in the
      communicative language test (MacArthur Communicative Development Inventories) at
      the age of two years. Thus, decline in sensitivity to non-native phonemes served
      as a predictor for further language development. CONCLUSION: Our data suggest
      that detrimental effects of prematurity on language skills are based on the low
      degree of specialization to native language early in development. Moreover,
      delayed or atypical perceptual narrowing was associated with slower language
      acquisition. The results hence suggest that language problems related to
      prematurity may partially originate already from this early tuning stage of
      language acquisition.

PMID- 20673358
TI  - Retrospective agreement and consent to neurocritical care is influenced by
      functional outcome.
AB  - INTRODUCTION: Only limited data are available on consent and satisfaction of
      patients receiving specialized neurocritical care. In this study we (i) analyzed
      the extent of retrospective consent to neurocritical care--given by patients or
      their relatives--depending on functional outcome one year after hospital stay,
      and (ii) identified predisposing factors for retrospective agreement to
      neurocritical care. METHODS: We investigated 704 consecutive patients admitted to
      a nonsurgical neurocritical care unit over a period of 2 years (2006 through
      2007). Demographic and clinical parameters were analyzed, and the patients were
      grouped according to their diagnosis. Functional outcome, retrospective consent
      to neurocritical care, and satisfaction with hospital stay was obtained by mailed
      standardized questionnaires. Logistic regression analyses were calculated to
      determine independent predictors for consent. RESULTS: High consent and
      satisfaction after neurointensive care (91% and 90%, respectively) was observed
      by those patients who reached an independent life one year after neurointensive
      care unit (ICU) stay. However, only 19% of surviving patients who were
      functionally dependent retrospectively agreed to neurocritical care. Unfavorable
      functional outcome and the diagnosis of stroke were independent predictors for
      missing retrospective consent. CONCLUSIONS: Retrospective agreement to
      neurocritical care is influenced by functional outcome. Especially in severely
      affected stroke patients who cannot communicate their preferences regarding life
      sustaining therapy, neurocritical care physicians should balance the expected
      burdens and benefits of treatment to meet the patients' putative wishes. Efforts
      should be undertaken to identify predictors for severe disability after
      neurocritical care.

PMID- 20673359
TI  - Sampling and pyrosequencing methods for characterizing bacterial communities in
      the human gut using 16S sequence tags.
AB  - Intense interest centers on the role of the human gut microbiome in health and
      disease, but optimal methods for analysis are still under development. Here we
      present a study of methods for surveying bacterial communities in human feces
      using 454/Roche pyrosequencing of 16S rRNA gene tags. We analyzed fecal samples
      from 10 individuals and compared methods for storage, DNA purification and
      sequence acquisition. To assess reproducibility, we compared samples one cm apart
      on a single stool specimen for each individual. To analyze storage methods, we
      compared 1) immediate freezing at -80 degrees C, 2) storage on ice for 24 or 3)
      48 hours. For DNA purification methods, we tested three commercial kits and bead
      beating in hot phenol. Variations due to the different methodologies were
      compared to variation among individuals using two approaches--one based on
      presence-absence information for bacterial taxa (unweighted UniFrac) and the
      other taking into account their relative abundance (weighted UniFrac). In the
      unweighted analysis relatively little variation was associated with the different
      analytical procedures, and variation between individuals predominated. In the
      weighted analysis considerable variation was associated with the purification
      methods. Particularly notable was improved recovery of Firmicutes sequences using
      the hot phenol method. We also carried out surveys of the effects of different
      454 sequencing methods (FLX versus Titanium) and amplification of different 16S
      rRNA variable gene segments. Based on our findings we present recommendations for
      protocols to collect, process and sequence bacterial 16S rDNA from fecal samples-
      some major points are 1) if feasible, bead-beating in hot phenol or use of the
      PSP kit improves recovery; 2) storage methods can be adjusted based on
      experimental convenience; 3) unweighted (presence-absence) comparisons are less
      affected by lysis method.

PMID- 20673360
TI  - Radiotherapy with or without chemotherapy for patients with T1-T2 glottic
      carcinoma: retrospective analysis.
AB  - BACKGROUND: To assess the results for local control (LC) and survival in patients
      with early-stage glottic cancer (GC) who were treated by radiotherapy (RT) with
      or without chemotherapy. METHODS: Fifty-eight patients with T1-T2 squamous cell
      carcinoma of the glottis who were treated between 2001 and 2006 were analyzed
      retrospectively. Potential prognostic factors for LC were evaluated by univariate
      analysis. RESULTS: The 5-year LC rate in all patients was 84.3%. The overall 5
      year LC rates for patients with T1a, Tb, and T2 GC were 85.9%, 83%, and 85%,
      respectively. Of the 58 patients, eight developed recurrent disease at the
      primary site, and one had lymph node recurrences on the neck. In the final
      analysis, the total laryngectomy-free survival rate was 93% at five years, and
      the ultimate LC rates for T1a, Tb, and T2 were 100%, 90.9%, and 95.2%,
      respectively. In a univariate analysis of 55 patients, there was no statistical
      significance between the LC rate for RT alone and that for chemoradiation. Only
      two patients died of laryngeal carcinoma, and one died of intercurrent disease.
      Fifty-five patients were living disease-free at the end of the study period. The
      5-year overall survival (OS) rate for all patients was 88.1%, and the 5-year OS
      rates for T1a, Tb, and T2 were 91.6%, 77.8%, and 89.9%, respectively.
      CONCLUSIONS: The retrospective analysis showed a high rate of LC and larynx
      preservation in patients with T1-T2 GC by means of RT with or without
      chemotherapy. There was, however, no statistical difference in LC rates for the
      two types of therapy.

PMID- 20673361
TI  - Cervical collagen and biomechanical strength in non-pregnant women with a history
      of cervical insufficiency.
AB  - BACKGROUND: It has been suggested that cervical insufficiency (CI) is
      characterized by a "muscular cervix" with low collagen and high smooth muscle
      concentrations also in the non-pregnant state. Therefore, the aim of this study
      was to investigate the biomechanical properties, collagen concentration, smooth
      muscle cell density, and collagen fiber orientation in cervical biopsies from non
      pregnant women with a history of CI. METHODS: Cervical punch biopsies (2 x 15 mm)
      were obtained from 57 normal non-pregnant women and 22 women with a history of
      CI. Biomechanical tensile testing was performed, and collagen content was
      determined by hydroxyproline quantification. Histomorphometry was used to
      determine the volume densities of extracellular matrix and smooth muscle cells
      from the distal to the proximal part of each sample. Smooth muscle cells were
      identified using immunohistochemistry. Finally, collagen fiber orientation was
      investigated. Data are given as mean +/- SD. RESULTS: Collagen concentration was
      lower in the CI group (58.6 +/- 8.8%) compared with the control group (62.2 +/-
      6.6%) (p = 0.033). However, when data were adjusted for age and parity, no
      difference in collagen concentration was found between the two groups. Maximum
      load of the specimens did not differ between the groups (p = 0.78). The tensile
      strength of cervical collagen, i.e. maximum load normalized per unit collagen (mg
      of collagen per mm of specimen length), was increased in the CI group compared
      with controls (p = 0.033). No differences in the volume density of extracellular
      matrix or smooth muscle cells were found between the two groups. Fibers not
      oriented in the plane of sectioning were increased in CI patients compared with
      controls. CONCLUSIONS: Cervical insufficiency does not appear to be associated
      with a constitutionally low collagen concentration or collagen of inferior
      mechanical quality. Furthermore, the hypothesis that a "muscular cervix" with an
      abundance of smooth muscle cells contributes to the development of cervical
      insufficiency is not supported by the present study.

PMID- 20673362
TI  - Characterization of two Runx1-dependent nociceptor differentiation programs
      necessary for inflammatory versus neuropathic pain.
AB  - BACKGROUND: The cellular and molecular programs that control specific types of
      pain are poorly understood. We reported previously that the runt domain
      transcription factor Runx1 is initially expressed in most nociceptors and
      controls sensory neuron phenotypes necessary for inflammatory and neuropathic
      pain. RESULTS: Here we show that expression of Runx1-dependent ion channels and
      receptors is distributed into two nociceptor populations that are distinguished
      by persistent or transient Runx1 expression. Conditional mutation of Runx1 at
      perinatal stages leads to preferential impairment of Runx1-persistent nociceptors
      and a selective defect in inflammatory pain. Conversely, constitutive Runx1
      expression in Runx1-transient nociceptors leads to an impairment of Runx1
      transient nociceptors and a selective deficit in neuropathic pain. Notably, the
      subdivision of Runx1-persistent and Runx1-transient nociceptors does not follow
      the classical nociceptor subdivision into IB4+ nonpeptidergic and IB4-
      peptidergic populations. CONCLUSION: Altogether, we have uncovered two distinct
      Runx1-dependent nociceptor differentiation programs that are permissive for
      inflammatory versus neuropathic pain. These studies lend support to a
      transcription factor-based distinction of neuronal classes necessary for
      inflammatory versus neuropathic pain.

PMID- 20673363
TI  - Human isolates of Bartonella tamiae induce pathology in experimentally inoculated
      immunocompetent mice.
AB  - BACKGROUND: Bartonella tamiae, a newly described bacterial species, was isolated
      from the blood of three hospitalized patients in Thailand. These patients
      presented with headache, myalgia, anemia, and mild liver function abnormalities.
      Since B. tamiae was presumed to be the cause of their illness, these isolates
      were inoculated into immunocompetent mice to determine their relative
      pathogenicity in inducing manifestations of disease and pathology similar to that
      observed in humans. METHODS: Three groups of four Swiss Webster female mice aged
      15-18 months were each inoculated with 10(6-7) colony forming units of one of
      three B. tamiae isolates [Th239, Th307, and Th339]. A mouse from each
      experimental group was sampled at 3, 4, 5 and 6 weeks post-inoculation. Two
      saline inoculated age-matched controls were included in the study. Samples
      collected at necropsy were evaluated for the presence of B. tamiae DNA, and
      tissues were formalin-fixed, stained with hematoxylin and eosin, and examined for
      histopathology. RESULTS: Following inoculation with B. tamiae, mice developed
      ulcerative skin lesions and subcutaneous masses on the lateral thorax, as well as
      axillary and inguinal lymphadenopathy. B. tamiae DNA was found in subcutaneous
      masses, lymph node, and liver of inoculated mice. Histopathological changes were
      observed in tissues of inoculated mice, and severity of lesions correlated with
      the isolate inoculated, with the most severe pathology induced by B. tamiae
      Th239. Mice inoculated with Th239 and Th339 demonstrated myocarditis,
      lymphadenitis with associated vascular necrosis, and granulomatous hepatitis and
      nephritis with associated hepatocellular and renal necrosis. Mice inoculated with
      Th307 developed a deep dermatitis and granulomas within the kidneys. CONCLUSIONS:
      The three isolates of B. tamiae evaluated in this study induce disease in
      immunocompetent Swiss Webster mice up to 6 weeks after inoculation. The human
      patients from whom these isolates were obtained had clinical presentations
      consistent with the multi-organ pathology observed in mice in this study. This
      mouse model for B. tamiae induced disease not only strengthens the causal link
      between this pathogen and clinical illness in humans, but provides a model to
      further study the pathological processes induced by these bacteria.

PMID- 20673364
TI  - Contralateral acupuncture versus ipsilateral acupuncture in the rehabilitation of
      post-stroke hemiplegic patients: a systematic review.
AB  - BACKGROUND: Contralateral acupuncture (CAT) involves inserting needles in the
      meridian on the side opposite the disease location and is often used in post
      stroke rehabilitation. The aim of this systematic review is to summarize and
      critically evaluate the evidence for and against the effectiveness of CAT for
      post-stroke rehabilitation as compared to ipsilateral acupuncture (IAT). METHODS:
      Seventeen databases were searched from their inceptions through June 2010.
      Prospective clinical trials were included if CAT was tested as the sole treatment
      or as an adjunct to other treatments for post-stroke rehabilitation and compared
      to IAT. RESULTS: Eight randomized clinical trials (RCTs) met our inclusion
      criteria. Four of them reported favorable effects of CAT compared to IAT for at
      least one outcome. A meta-analysis showed superior effects of CAT compared to IAT
      on recovery rate (n = 361; risk ratio (RR), 1.12; 95% confidence intervals (CIs),
      1.04 to 1.22, P = 0.005). Subgroup analysis also showed favorable effects of
      using CAT on patients with cerebral infarction (n = 261; RR, 1.15; 95% CIs, 1.04
      to 1.27, P = 0.006). Further analysis including patients with cerebral infarction
      and intracranial hemorrhage, however, failed to show these advantages (n = 100;
      RR, 1.11; 95% CIs, 0.85 to 1.46, P = 0.43). CONCLUSION: The results of our
      systematic review and meta-analysis suggest that there is limited evidence for
      CAT being superior to IAT in the treatment of cerebral infarction. The total
      number of RCTs included in our analysis was low, however, and the RCTs included
      had a high risk of bias. Future RCTs appear to be warranted.

PMID- 20673365
TI  - A meta-analysis for the effect of prophylactic GTN on the incidence of post-ERCP
      pancreatitis and on the successful rate of cannulation of bile ducts.
AB  - BACKGROUND: Glyceryl trinitrate (GTN) has been shown to be able to relax the
      sphincter of Oddi (SO) both in animals and humans. Theoretically, the use of
      these compounds during and after endoscopic retrograde cholangiopancreatgraphy
      (ERCP) could relax the biliary and pancreatic sphincters, facilitating
      cannulation of common bile duct (CBD) during the procedure, or minimizing
      potential pancreatic outflow obstruction after the procedure. However, clinical
      trials evaluating the protective effect of GTN on the post-endoscopic retrograde
      cholangiopancreatgraphy pancreatitis (PEP) have yielded inconclusive results.
      This meta-analysis is to systematically assess the effect of prophylactic
      administration of glyceryl trinitrate (GTN) on the prevention of PEP and the
      effect on the cannulation of bile ducts. METHODS: By searching PubMed (1966 to
      September 2009), CENTRAL (Cochrane Controlled trials Register; issue 3, 2009) and
      EMBASE.com (1984 to September 2009), two independent reviewers systematically
      identified prospective randomized controlled trials (RCTs) detecting the effect
      of prophylactic GTN on the incidence of PEP and on the cannulation of bile ducts.
      A meta-analysis of these clinical trials was then performed. RESULTS: There are
      55/899(6.1%) patients suffering PEP in the treatment group versus 95/915(10.4%)
      patients in the placebo group. The overall pooled risk of PEP was significantly
      lower in the GTN group than in the placebo group (OR 0.56, 95% CI: 0.40 to 0.79,
      p = 0.001). Subgroup analyses suggested that GTN administered by the sublingual
      form (OR 0.34,95% CI:0.16 to 0.75, p = 0.007) is more effective than transdermal
      route(OR 0.64,95% CI:0.40 to 1.01, p = 0.05), and the protective effect of GTN
      was far more obvious in the centers with high incidence of PEP (OR 0.40, 95%
      CI:0.24 to 0.67, p = 0.0006) than those centers with a low incidence of PEP (OR
      0.75, 95% CI: 0.47 to 1.20, p = 0.22). Additionally, the meta-analysis suggests
      that GTN was not helpful for the cannulation of bile ducts. CONCLUSION: We
      concluded that prophylactic administration of GTN may significantly reduce the
      incidence of PEP and not be helpful for the cannulation of bile ducts.

PMID- 20673366
TI  - Differential activation of the lateral premotor cortex during action observation.
AB  - BACKGROUND: Action observation leads to neural activation of the human premotor
      cortex. This study examined how the level of motor expertise (expert vs. novice)
      in ballroom dancing and the visual viewpoint (internal vs. external viewpoint)
      influence this activation within different parts of this area of the brain.
      RESULTS: Sixteen dance experts and 16 novices observed ballroom dance videos from
      internal or external viewpoints while lying in a functional magnetic resonance
      imaging scanner. A conjunction analysis of all observation conditions showed that
      action observation activated distinct networks of premotor, parietal, and
      cerebellar structures. Experts revealed increased activation in the ventral
      premotor cortex compared to novices. An internal viewpoint led to higher
      activation of the dorsal premotor cortex. CONCLUSIONS: The present results
      suggest that the ventral and dorsal premotor cortex adopt differential roles
      during action observation depending on the level of motor expertise and the
      viewpoint.

PMID- 20673367
TI  - Malaria resurgence risk in southern Europe: climate assessment in an historically
      endemic area of rice fields at the Mediterranean shore of Spain.
AB  - BACKGROUND: International travel and immigration have been related with an
      increase of imported malaria cases. This fact and climate change, prolonging the
      period favouring vector development, require an analysis of the malaria
      transmission resurgence risk in areas of southern Europe. Such a study is made
      for the first time in Spain. The Ebro Delta historically endemic area was
      selected due to its rice field landscape, the presence of only one vector,
      Anopheles atroparvus, with densities similar to those it presented when malaria
      was present, in a situation which pronouncedly differs from already assessed
      potential resurgence areas in other Mediterranean countries, such as France and
      Italy, where many different Anopheles species coexist and a different vector
      species dominates. METHODS: The transmission risk was assessed analysing: 1)
      climate diagrams including the minimum temperature for Plasmodium falciparum and
      Plasmodium vivax development; 2) monthly evolution of the Gradient Model Risk
      (GMR) index, specifying transmission risk period and number of potential
      Plasmodium generations; 3) ecological characteristics using remote sensing images
      with the Eurasia Land Cover characteristics database and the monthly evolution of
      the Normalized Difference Vegetation Index (NDVI); 4) evaluation of A. atroparvus
      population dynamics. RESULTS: Climatological analyses and GMR index show that a
      transmission risk presently exists, lasting from May until September for P.
      falciparum, and from May until October for P. vivax. The GMR index shows that the
      temperature increase does not actually mean a transmission risk increase if
      accompanied by a precipitation decrease reducing the number of parasite
      generations and transmission period. Nevertheless, this limitation is offset by
      the artificial flooding of the rice fields. Maximum NDVI values and A. atroparvus
      maximum abundance correspond to months with maximum growth of the rice fields.
      CONCLUSIONS: The Ebro Delta presents the ecological characteristics that favour
      transmission. The temperature increase has favoured a widening of the monthly
      potential transmission window with respect to when malaria was endemic. The
      combined application of modified climate diagrams and GMR index, together with
      spatial characterization conforms a useful tool for assessing potential areas at
      risk of malaria resurgence. NDVI is a good marker when dealing with a rice field
      area.

PMID- 20673368
TI  - Predicting beta-turns and their types using predicted backbone dihedral angles
      and secondary structures.
AB  - BACKGROUND: Beta-turns are secondary structure elements usually classified as
      coil. Their prediction is important, because of their role in protein folding and
      their frequent occurrence in protein chains. RESULTS: We have developed a novel
      method that predicts beta-turns and their types using information from multiple
      sequence alignments, predicted secondary structures and, for the first time,
      predicted dihedral angles. Our method uses support vector machines, a supervised
      classification technique, and is trained and tested on three established datasets
      of 426, 547 and 823 protein chains. We achieve a Matthews correlation coefficient
      of up to 0.49, when predicting the location of beta-turns, the highest reported
      value to date. Moreover, the additional dihedral information improves the
      prediction of beta-turn types I, II, IV, VIII and "non-specific", achieving
      correlation coefficients up to 0.39, 0.33, 0.27, 0.14 and 0.38, respectively. Our
      results are more accurate than other methods. CONCLUSIONS: We have created an
      accurate predictor of beta-turns and their types. Our method, called DEBT, is
      available online at http://comp.chem.nottingham.ac.uk/debt/.

PMID- 20673369
TI  - Cdk5 phosphorylates non-genotoxically overexpressed p53 following inhibition of
      PP2A to induce cell cycle arrest/apoptosis and inhibits tumor progression.
AB  - BACKGROUND: p53 is the most studied tumor suppressor and its overexpression may
      or may not cause cell death depending upon the genetic background of the cells.
      p53 is degraded by human papillomavirus (HPV) E6 protein in cervical carcinoma.
      Several stress activated kinases are known to phosphorylate p53 and, among them
      cyclin dependent kinase 5 (Cdk5) is one of the kinase studied in neuronal cell
      system. Recently, the involvement of Cdk5 in phosphorylating p53 has been shown
      in certain cancer types. Phosphorylation at specific serine residues in p53 is
      essential for it to cause cell growth inhibition. Activation of p53 under non
      stress conditions is poorly understood. Therefore, the activation of p53 and
      detection of upstream kinases that phosphorylate non-genotoxically overexpressed
      p53 will be of therapeutic importance for cancer treatment. RESULTS: To determine
      the non-genotoxic effect of p53; Tet-On system was utilized and p53 inducible HPV
      positive HeLa cells were developed. p53 overexpression in HPV-positive cells did
      not induce cell cycle arrest or apoptosis. However, we demonstrate that
      overexpressed p53 can be activated to upregulate p21 and Bax which causes G2
      arrest and apoptosis, by inhibiting protein phosphatase 2A. Additionally, we
      report that the upstream kinase cyclin dependent kinase 5 interacts with p53 to
      phosphorylate it at Serine20 and Serine46 residues thereby promoting its
      recruitment on p21 and bax promoters. Upregulation and translocation of Bax
      causes apoptosis through intrinsic mitochondrial pathway. Interestingly,
      overexpressed activated p53 specifically inhibits cell-growth and causes
      regression in vivo tumor growth as well. CONCLUSION: Present study details the
      mechanism of activation of p53 and puts forth the possibility of p53 gene therapy
      to work in HPV positive cervical carcinoma.

PMID- 20673370
TI  - Development of the ATAQ-IPF: a tool to assess quality of life in IPF.
AB  - BACKGROUND: There is no disease-specific instrument to assess health-related
      quality of life (HRQL) in patients with idiopathic pulmonary fibrosis (IPF).
      METHODS: Patients' perspectives were collected to develop domains and items for
      an IPF-specific HRQL instrument. We used item variance and Rasch analysis to
      construct the ATAQ-IPF (A Tool to Assess Quality of life in IPF). RESULTS: The
      ATAQ-IPF version 1 is composed of 74 items comprising 13 domains. All items fit
      the Rasch model. Domains and the total instrument possess acceptable psychometric
      characteristics for a multidimensional questionnaire. The pattern of correlations
      between ATAQ-IPF scores and physiologic variables known to be important in IPF,
      along with significant differences in ATAQ-IPF scores between subjects using
      versus those not using supplemental oxygen, support its validity. CONCLUSIONS:
      Patient-centered and careful statistical methodologies were used to construct the
      ATAQ-IPF version 1, an IPF-specific HRQL instrument. Simple summation scoring is
      used to derive individual domain scores as well as a total score. Results support
      the validity of the ATAQ-IPF, and future studies will build on that validity.

PMID- 20673371
TI  - Gene genealogies indicates abundant gene conversions and independent evolutionary
      histories of the mating-type chromosomes in the evolutionary history of
      Neurospora tetrasperma.
AB  - BACKGROUND: The self-fertile filamentous ascomycete Neurospora tetrasperma
      contains a large (approximately 7 Mbp) and young (< 6 MYA) region of suppressed
      recombination within its mating-type (mat) chromosomes. The objective of the
      present study is to reveal the evolutionary history, including key genomic
      events, associated with the various regions of the mat chromosomes among ten
      strains representing all the nine known species (lineages) contained within the
      N. tetrasperma species complex. RESULTS: Comparative analysis of sequence
      divergence among alleles of 24 mat-linked genes (mat A and mat a) indicates that
      a large region of suppressed recombination exists within the mat chromosome for
      each of nine lineages of N. tetrasperma sensu latu. The recombinationally
      suppressed region varies in size and gene composition among lineages, and is
      flanked on both ends by normally recombining regions. Genealogical analyses among
      lineages reveals that eight gene conversion events have occurred between
      homologous mat A and mat a-linked alleles of genes located within the region of
      restricted recombination during the evolutionary history of N. tetrasperma.
      CONCLUSIONS: We conclude that the region of suppressed recombination in the mat
      chromosomes has likely been subjected to independent contraction and/or expansion
      during the evolutionary history of the N. tetrasperma species complex.
      Furthermore, we infer that gene conversion events are likely a common phenomenon
      within this recombinationally suppressed genomic region. We argue that gene
      conversions might provide an efficient mechanism of adaptive editing of
      functional genes, including the removal of deleterious mutations, within the
      young recombinationally suppressed region of the mat chromosomes.

PMID- 20673372
TI  - Impact of diastolic dysfunction severity on global left ventricular volumetric
      filling - assessment by automated segmentation of routine cine cardiovascular
      magnetic resonance.
AB  - OBJECTIVES: To examine relationships between severity of echocardiography (echo) 
      evidenced diastolic dysfunction (DD) and volumetric filling by automated
      processing of routine cine cardiovascular magnetic resonance (CMR). BACKGROUND:
      Cine-CMR provides high-resolution assessment of left ventricular (LV) chamber
      volumes. Automated segmentation (LV-METRIC) yields LV filling curves by
      segmenting all short-axis images across all temporal phases. This study used cine
      CMR to assess filling changes that occur with progressive DD. METHODS: 115 post
      MI patients underwent CMR and echo within 1 day. LV-METRIC yielded multiple
      diastolic indices - E:A ratio, peak filling rate (PFR), time to peak filling rate
      (TPFR), and diastolic volume recovery (DVR80 - proportion of diastole required to
      recover 80% stroke volume). Echo was the reference for DD. RESULTS: LV-METRIC
      successfully generated LV filling curves in all patients. CMR indices were
      reproducible (< or = 1% inter-reader differences) and required minimal processing
      time (175 +/- 34 images/exam, 2:09 +/- 0:51 minutes). CMR E:A ratio decreased
      with grade 1 and increased with grades 2-3 DD. Diastolic filling intervals,
      measured by DVR80 or TPFR, prolonged with grade 1 and shortened with grade 3 DD,
      paralleling echo deceleration time (p < 0.001). PFR by CMR increased with DD
      grade, similar to E/e' (p < 0.001). Prolonged DVR80 identified 71% of patients
      with echo-evidenced grade 1 but no patients with grade 3 DD, and stroke-volume
      adjusted PFR identified 67% with grade 3 but none with grade 1 DD (matched
      specificity = 83%). The combination of DVR80 and PFR identified 53% of patients
      with grade 2 DD. Prolonged DVR80 was associated with grade 1 (OR 2.79, CI 1.65
      4.05, p = 0.001) with a similar trend for grade 2 (OR 1.35, CI 0.98-1.74, p =
      0.06), whereas high PFR was associated with grade 3 (OR 1.14, CI 1.02-1.25, p =
      0.02) DD. CONCLUSIONS: Automated cine-CMR segmentation can discern LV filling
      changes that occur with increasing severity of echo-evidenced DD. Impaired
      relaxation is associated with prolonged filling intervals whereas restrictive
      filling is characterized by increased filling rates.

PMID- 20673373
TI  - Measuring the context of care in an Australian acute care hospital: a nurse
      survey.
AB  - BACKGROUND: This study set out to achieve three objectives: to test the
      application of a context assessment tool in an acute hospital in South Australia;
      to use the tool to compare context in wards that had undergone an evidence
      implementation process with control wards; and finally to test for relationships
      between demographic variables (in particular experience) of nurses being studied
      (n = 422) with the dimensions of context. METHODS: The Alberta Context Tool (ACT)
      was administered to all nursing staff on six control and six intervention wards.
      A total of 217 (62%) were returned (67% from the intervention wards and 56% from
      control wards). Data were analysed using Stata (v9). The effect of the
      intervention was analysed using nested (hierarchical) analysis of variance;
      relationships between nurses' experience and context was examined using canonical
      correlation analysis. RESULTS: Results confirmed the adaptation and fit of the
      ACT to one acute care setting in South Australia. There was no difference in
      context scores between control and intervention wards. However, the tool
      identified significant variation between wards in many of the dimensions of
      context. Though significant, the relationship between nurses' experience and
      context was weak, suggesting that at the level of the individual nurse, few
      factors are related to context. CONCLUSIONS: Variables operating at the level of
      the individual showed little relationship with context. However, the study
      indicated that some dimensions of context (e.g., leadership, culture) vary at the
      ward level, whereas others (e.g., structural and electronic resources) do not.
      The ACT also raised a number of interesting speculative hypotheses around the
      relationship between a measure of context and the capability and capacity of
      staff to influence it.We propose that context be considered to be dependent on
      ward- and hospital-level factors. Additionally, questions need to be considered
      about the unit of measurement of context in studies of knowledge implementation-
      is individual (micro), ward (meso) or hospital-level (macro) data most
      appropriate? The preliminary results also raise questions about how best to
      utilise this instrument in knowledge translation research.

PMID- 20673374
TI  - Intentions to use contraceptives in Pakistan: implications for behavior change
      campaigns.
AB  - BACKGROUND: Since 1990-91, traditional method use has increased at a faster rate
      in Pakistan than modern method use. The importance of hormonal methods or the IUD
      has diminished and that of traditional methods has increased in the method mix.
      There is a need to identify factors motivating and deterring the adoption of
      specific family planning methods among married men and women in Pakistan.
      METHODS: In addition to social and demographic characteristics of respondents, a
      representative household survey collected information on psychological correlates
      of family planning behavior from 1,788 non-pregnant wives and 1,805 husbands with
      not-pregnant wives. Males and females were from separate households. Principal
      components analysis was conducted to identify the underlying constructs that were
      important for each gender. Multinomial logistic regression analysis was conducted
      to determine the correlates of male and female intentions to use contraceptive
      methods. RESULTS: Amongst women, the perception that her in-laws support family
      planning use was the strongest determinant of her intentions to use contraceptive
      methods. A woman's belief in the importance of spacing children and her
      perception that a choice of methods and facilities with competent staff were
      available were also powerful drivers of her intentions to use contraceptive
      methods. The strongest obstacle to a woman's forming an intention to use
      contraceptive methods was her belief that family planning decisions were made by
      the husband and fertility was determined by God's will. Fears that family
      planning would harm a woman's womb lowered a woman's intentions to use methods
      requiring procedures, such as the IUD and female sterilization.The perception
      that a responsible, caring, husband uses family planning to improve the standard
      of living of his family and to protect his wife's health was the most important
      determinant of a man's intention to use condoms. A husband's lack of self
      efficacy in being able to discuss family planning with his wife was the strongest
      driver of the intention to use withdrawal. A man's fear that contraceptives would
      make a woman sterile and harm her womb lowered his intention to use modern
      contraceptive methods. CONCLUSIONS: These findings highlight the importance of
      having secondary target audiences such as mothers-in-law and husbands in family
      planning behavior change campaigns implemented in Pakistan. Campaigns that stress
      the importance of child spacing are likely to have an impact. Client perceptions
      of the quality of care are important determinants of intentions to use
      contraceptive methods in Pakistan. Client concerns that the IUD and sterilization
      procedures might harm a woman's womb and cause sterility should be addressed. The
      findings suggest that there is a need to assess the actual quality of service
      delivery in Pakistan.

PMID- 20673375
TI  - C-reactive protein levels: a prognostic marker for patients with head and neck
      cancer?
AB  - BACKGROUND: Recent advances in understanding complex tumor interactions have led
      to the discovery of an association between inflammation and cancer, in particular
      for colon and lung cancer, but only a very few have dealt with oral cancer.
      Therefore, the aim of the current study was to investigate the significance of
      preoperative C-reactive protein (CRP) levels as a parameter for development of
      lymph node metastases or recurrence. MATERIALS AND METHODS: In 278 patients with
      oral cancer, preoperative CRP levels were compared with development of recurrence
      and metastasis. RESULTS: In 27 patients from the normal CRP group, and in 21
      patients from the elevated CRP group, local recurrence was observed. Concerning
      lymph node metastases, 37 patients were in the normal group and 9 patients in the
      elevated CRP group. No significant correlation could be found between elevated
      CRP levels and metastasis (p = 0.468) or recurrence (p = 0.137). CONCLUSION: Our
      findings do not appear to support a correlation between preoperative CRP levels
      and development of recurrence or metastases. In further studies, CRP levels in
      precancerous lesions and in Human Papilloma Virus (HPV) positive patients with
      oral squamous cell carcinoma (SCC) should be studied.

PMID- 20673376
TI  - A polyphenol extract modifies quantity but not quality of liver fatty acid
      content in high-fat-high-sucrose diet-fed rats: possible implication of the
      sirtuin pathway.
AB  - High-fat or high-fat-high-sucrose diets are known to induce non-alcoholic fatty
      liver disease and this is emerging as one of the most common liver diseases
      worldwide. Some polyphenols have been reported to decrease rat hepatic lipid
      accumulation, in particular those extracted from red grapes such as resveratrol.
      The present study was designed to determine whether a polyphenol extract (PPE),
      from red grapes, modulates liver fatty acid composition and desaturase activity
      indexes in rats fed a high-fat-high-sucrose (HFHS) diet, and to explore whether
      sirtuin-1 deacetylase activation was implicated in the effect of the PPE against
      liver steatosis. The effect of this PPE on mitochondriogenesis and mitochondrial
      activity was also explored. The PPE decreased liver TAG content in HFHS+PPE diet
      fed rats in comparison with HFHS diet-fed rats. The PPE had no effect on liver
      fatty acid composition, desaturase activity indexes and stearoyl-CoA desaturase 1
      (SCD1) gene expression. Sirtuin-1 deacetylase protein expression was
      significantly increased with the PPE; AMP kinase protein expression was higher
      with the PPE in comparison with the HFHS rats, but no modification of
      phosphorylated AMP kinase was observed. Protein expression of phospho-acetyl-CoA
      carboxylase was decreased in HFHS rats and returned to basal values with the PPE.
      Finally, the PPE modulated PPARgamma coactivator-1alpha (PGC-1alpha) but did not
      modify mitochondriogenesis and mitochondrial activity. In conclusion, the PPE
      partially prevented the accumulation of TAG in the liver by regulating acetyl-CoA
      carboxylase phosphorylation, a key enzyme in lipid metabolism, probably via
      sirtuin-1 deacetylase activation. However, the PPE had no effect on the
      qualitative composition of liver fatty acids.

PMID- 20673377
TI  - Comparison of different maximum safe levels in fortified foods and supplements
      using a probabilistic risk assessment approach.
AB  - Different European institutions have developed mathematical models to propose
      maximum safe levels either for fortified foods or for dietary supplements. The
      objective of the present study was to compare and check the safety of these
      different maximum safe levels (MSL) by using a probabilistic risk assessment
      approach. The potential maximum nutritional intakes were estimated by taking into
      account all sources of intakes (base diet, fortified foods and dietary
      supplements) and compared with the tolerable upper intake levels for vitamins and
      minerals. This approach simulated the consequences of both food fortification and
      supplementation in terms of food safety. Different scenarios were tested. They
      are the result of the combination of several MSL obtained using the previous
      models. The study was based on the second French Individual and National Study on
      Food Consumption performed in 2006-7, matched with the French food nutritional
      composition database. The analyses were based on a sample of 1918 adults aged 18
      79 years. Some MSL in fortified foods and dietary supplements obtained
      independently were protective enough, although some others could lead to
      nutritional intakes above the tolerable upper intake levels. The simulation
      showed that it is crucial to consider the inter-individual variability of
      fortified food intakes when setting MSL for foods and supplements. The risk
      assessment approach developed here by integrating the MSL for fortified foods and
      dietary supplements is useful for ensuring consumer protection. It may be
      subsequently used to test any other MSL for vitamins and minerals proposed in the
      future.

PMID- 20673378
TI  - Increased potassium intake from fruit and vegetables or supplements does not
      lower blood pressure or improve vascular function in UK men and women with early
      hypertension: a randomised controlled trial.
AB  - K-rich fruit and vegetables may lower blood pressure (BP) and improve vascular
      function. A randomised controlled trial (ISRCTN50011192) with a cross-over design
      was conducted in free-living participants with early stages of hypertension
      (diastolic BP>80 and < 100 mmHg, not receiving BP-lowering medication) to test
      this hypothesis. Following a 3-week run-in period on a control diet, each subject
      completed four dietary 6-week dietary interventions (control+placebo capsules, an
      additional 20 or 40 mmol K(+)/d from fruit and vegetables or 40 mmol potassium
      citrate capsules/d) using a Latin square design with a washout period >= 5 weeks
      between the treatment periods. Out of fifty-seven subjects who were randomised,
      twenty-three male and twenty-five female participants completed the study;
      compliance to the intervention was corroborated by food intake records and
      increased urinary K(+) excretion; plasma lipids, vitamin C, folate and
      homocysteine concentrations, urinary Na excretion, and body weight remained were
      unchanged. On the control diet, mean ambulatory 24 h systolic/diastolic BP were
      132.3 (sd 12.0)/81.9 ((SD) 7.9) mmHg, and changes (Bonferroni's adjusted 95 % CI)
      compared with the control on the diets providing 20 and 40 mmol K(+)/d as fruit
      and vegetables were 0.8 (- 3.5, 5.3)/0.8 (- 1.9, 3.5) and 1.7 (- 3.0, 5.3)/1.5 (-
      1.5, 4.4), respectively, and were 1.8 (- 2.1, 5.8)/1.4 (- 1.6, 4.4) mmHg on the
      40 mmol potassium citrate supplement, and were not statistically significant.
      Arterial stiffness, endothelial function, and urinary and plasma isoprostane and
      C-reactive protein (CRP) concentrations did not differ significantly between the
      diets. The present study provides no evidence to support dietary advice to
      increase K intake above usual UK intakes in the subjects with early stages of
      hypertension.

PMID- 20673379
TI  - Phaseolin from Phaseolus vulgaris bean modulates gut mucin flow and gene
      expression in rats.
AB  - Dietary protein might modulate mucin flow and intestinal mucin gene expression.
      Since unheated phaseolin from Phaseolus vulgaris bean is resistant to digestion
      and increases gut endogenous protein losses, we hypothesised that unheated
      phaseolin influences mucin flow and gene expression, and that phaseolin heat
      treatment reverses these effects. The hypothesis was tested using a control diet
      containing casein as the sole protein source and three other diets with casein
      being replaced by 33 and 67 % of unheated and 67 % of heated phaseolin. The rats
      were fed for 6 d and euthanised. Digesta and faeces were collected for
      determining digestibility and mucin flow. Gut tissues were collected for mucin
      (Muc1, Muc2, Muc3 and Muc4) and Trefoil factor 3 (Tff3) gene expressions. Colonic
      mucin flow decreased linearly with increasing the dietary level of unheated
      phaseolin (P < 0.05). Unheated phaseolin increased N flow in ileum, colon and
      faeces (P < 0.05), and reduced apparent N digestibility linearly (P < 0.01). Heat
      treatment reversed all these changes (P < 0.05 to < 0.001), except mucin flow.
      The expressions of Muc mRNA in gut tissues were influenced by dietary phaseolin
      level (ileum and colon: Muc3 and Muc4) and thermal treatment (ileum: Muc2; colon:
      Muc2, Muc3, Muc4 and Tff3) (P < 0.05 to 0.001). In conclusion, phaseolin
      modulates mucin flow and Muc gene expression along the intestines differentially.

PMID- 20673380
TI  - Molecular mechanisms controlling human adipose tissue development: insights from
      monogenic lipodystrophies.
AB  - Appropriately functioning adipose tissue is essential for human health, a fact
      most clearly illustrated by individuals with lipodystrophy, who have impaired
      adipose development and often suffer severe metabolic disease as a result. Humans
      with obesity display a similar array of metabolic problems. This reflects
      failures in fat tissue function in obesity, which results in consequences similar
      to those seen when insufficient adipose tissue is present. Thus a better
      understanding of the molecules that regulate the development of fat tissue is
      likely to aid the generation of novel therapeutic strategies for the treatment of
      all disorders of altered fat mass. Single gene disruptions causing lipodystrophy
      can give unique insights into the importance of the proteins they encode in human
      adipose tissue development. Moreover, the mechanisms via which they cause
      lipodystrophy can reveal new molecules and pathways important for adipose tissue
      development and function as well as confirming the importance of molecules
      identified from studies of cellular and animal models.

PMID- 20673381
TI  - Selective review of cognitive aging.
AB  - Research concerned with relations between adult age and cognitive functioning is
      briefly reviewed. The coverage is necessarily selective, and is organized in
      terms of five major questions. These are what abilities are related to age, how
      many distinct influences are contributing to the relations between age and
      cognitive functioning, do the differences between people increase with advancing
      age, what is responsible for the discrepancies between cross-sectional and
      longitudinal age comparisons of cognitive functioning, and what methods can be
      used to identify causes of age-related influences on cognition. Although
      definitive answers are not yet possible, quite a bit of information relevant to
      the questions is now available. Moreover, the existing information has
      implications for the design, analysis, and interpretation of cognitive and
      neuropsychological research concerned with aging.

PMID- 20673382
TI  - My head hurts just thinking about it.

PMID- 20673383
TI  - Finger millet in nutrition transition: an infant weaning food ingredient with
      chronic disease preventive potential.

PMID- 20673384
TI  - Dietary supplements, quality scores and missing data in the review of validation
      studies.

PMID- 20673386
TI  - Editorial. Training in Neuroradiology in Europe. Report of the Seminar held in
      Venice, June 1997.

PMID- 20673387
TI  - Transforming growth factor-Beta binds reversibly in vitro to guglielmi detachable
      coils.
AB  - SUMMARY: We determined the propensity for and reversibility of transforming
      growth factor-beta(TGFbeta) binding to uncoated Guglielmi Detachable Coils (GDC)
      and to GDC coated with extracellular matrix (ECM) proteins. Three 1.0 centimetre
      samples each of uncoated GDC-18 and of GDC-18 coated with either poly-L-lysine,
      laminin, type I collagen, type IV collagen, fibronectin, or poly-L-lysine and
      laminin were prepared. These samples were immersed briefly in a solution
      containing I(125)-labelled TGFbeta at a concentration of 0.225 mug/ml with
      initial specific activity of 123.3 mCi/mg (DuPont-NEN, Billerica, MA), and were
      counted using a scintillation counter. Each sample was then placed in a vial
      containing saline, shaken for 60 seconds, and counted again. Selected samples
      were immersed for varying periods within the TGFbeta solution and counted before
      and after saline rinse. Samples were rinsed one week after initial rinsing and
      counted again. The amount of binding between coil types was compared using the
      Student t test. For all samples initial binding of TGFbeta was in the order of 60
      120 pg/cm. For the pre-rinse data there were no statistically significant
      differences between the amount bound to any single coil coating type relative to
      other coatings. Compared to the initial accumulations, the amount remaining after
      rinsing ranged from 40% (poly-L-lysine) to 63% (poly-L-lysine with laminin), with
      a mean of 55% among the seven coil types. After rinsing there was more growth
      factor remaining on uncoated coils than on poly-L-lysine-coated coils (p=0.05),
      fibronectin-coated coils (p=0.01), and type IV collagen-coated coils (p=0.04).
      There was a trend toward greater residual growth factor on coils coated with poly
      L-lysine and laminin compared to coils coated with poly-L-lysine alone (p=0.10).
      Delayed, second rinsing of the samples one week after initial testing
      demonstrated only minor incremental loss of TGFbeta from the coil surfaces. After
      five minutes of immersion, accumulation was approximately 200% greater than that
      noted with brief submersion, but immersions lasting over five minutes did not
      yield increasing levels of TGFbeta binding. TGFbeta binds to GDC coils. Binding
      is not improved with ECM protein-coated coils compared to uncoated coils. The
      absolute amount of TGFbeta bound to the coil will likely result in local
      concentrations of growth factor in the order of those required for biological
      activity in vivo.

PMID- 20673388
TI  - Assessment of Complication Types and Rates Related to Diagnostic Angiography and
      Interventional N euroradiologic Procedures. A Four Year Review (1993-1996).
AB  - SUMMARY: We determined the types and rates of complications related to diagnostic
      angiography and neuroradiologic interventional procedures at a centre that
      carries out the full spectrum of angiographic procedures. The occurrence of
      immediate and delayed complications in 1929 neuroangiographic procedures (1358
      diagnostic and 571 interventional) performed between the years 1993-1996 was
      prospectively identified and recorded on a daily basis. A retrospective review of
      all charts of patients having procedures conducted during the study period was
      also carried out to ensure that no complications were missed. The overall
      complication rate for diagnostic cerebral angiography was 2.2%. Puncture site
      complications ranged from 0 - 0.1 %. Vessel injury distal to the puncture site
      ranged from 0.2 - 0.6%. The temporary neurologic complication rate was 0.3%,
      while the permanent rate was 0.4%. There were no contrast reactions. The death
      rate was 0.1 %. Interventional procedures had higher incidences of complications
      with overall rates ranging from 5.3 - 33%. Temporary and permanent neurologic
      deficits occurred at a rate of 0 - 10.5% depending upon the procedure involved.
      Individual complication and death rates and complication categories are provided
      for arteriovenous malformation embolisation, tumour embolisation, temporary
      balloon occlusion tests, detachable balloon vessel sacrifice, urokinase infusion,
      angioplasty, papavarine infusion, GDC embolisation, and carotid cavernous fistula
      embolisation. When carried out in experienced hands, neuroangiography and
      neurointervention are relatively safe with low incidences of neurologic and non
      neurologic complications. Knowledge of these rates is important when counselling
      patients prior to treatments or deciding upon the risk-benefit ratio of
      preoperative procedures.

PMID- 20673389
TI  - The nature of early intraluminal thrombosis in terminal aneurysms occluded with
      guglielmi detachable coils.
AB  - SUMMARY: To investigate the early intraluminal thrombotic events after
      endovascular treatment of terminal aneurysms with detachable coils, and to assess
      the biological changes over the first three weeks, terminal arterial bifurcation
      aneurysms were produced microsurgically in 20 rabbits. After a healing period of
      three weeks, transfemoral angiography was performed and all aneurysms were
      occluded with Guglielmi Detachable Coils (GDC). Complete (i.e. 100%) occlusion
      was achieved in ten aneurysms. About 95% occlusion (only a small neck remnant)
      was seen in eight cases. In two cases, occlusion was about 70 - 80%. Half of the
      animals were treated by anticoagulation during and continuously two days after
      occlusion therapy. Angiographic studies and histological analysis were done for
      four aneurysms (two without and two with anticoagulation) after 24 - 48 hours, 3 
      4 days, 6 - 7 days, 14 days, and 21 days after the treatment. On macroscopic
      examination, complete occlusion of the aneurysms by early thrombus formation was
      found in all cases during the first two days. After three to seven days,
      recanalization and fibrinolysis were observed, leading to a reopening of the
      neck, and part of the dome. After three weeks recanalization was found in six out
      of eight aneurysms, regardless of whether the animal was under anticoagulation.
      In nine cases, the degree of occlusion was overestimated by angiography compared
      to the pathological findings. During the early phase after occlusion of an
      aneurysm with platinum coils, extensive clot formation is induced. Over time due
      to the natural fibrinolysis, continuous recanalization beginning at the neck
      takes place. These findings can explain the clinical phenomenon of early
      thromboembolic complications, and the reopening and regrowth of aneurysms
      occluded with metallic coils observed at later stages.

PMID- 20673390
TI  - Correlation of Continuous EEG Monitoring with [O-l5]H2O Positron Emission
      Tomography Determination of Cerebral Blood Flow during Balloon Test Occlusion of
      the Internal Carotid Artery. Experience in 34 cases.
AB  - SUMMARY: The purpose of this paper was to evaluate the utility of continuous
      electroencephalography (EEG) during balloon test occlusion (BTO) of the internal
      carotid artery (ICA). Continuous EEG monitoring and [O-15] H2O PET cerebral blood
      flow (CBF) studies were completed in 34 patients undergoing BTO of the ICA. CBF
      determinations were obtained as a baseline without carotid occlusion, and
      following balloon occlusion, with continuous EEG monitoring. Patients were
      divided into three groups based on clinical and CBF response to BTO. Group I had
      no clinical signs or symptoms and had a CBF decrease less than 10 ml/l00 g/min
      ipsilateral to the occlusion. Group II had no symptoms but CBF fell to 35 to 25
      ml/l00 g/min on the occluded side. Group III were clinically unable to tolerate
      occlusion or CBF fell to less than 25 ml/l00 g/min on the occluded side. The
      results of continuous 21 channel EEG monitoring were assessed at the time of the
      examination and retrospectively reviewed for changes in the EEG pattern
      indicative of ischaemia. On the basis of PET CBF, eighteen patients were
      classified as Group I, four as Group II, and twelve as Group III. EEG evidence of
      ischaemia was seen in three patients, all members of Group III. Of the three
      patients, only one patient had clinical signs or symptoms of ischaemia. All four
      patients in Group II had PET quantitated CBF levels indicating carotid sacrifice
      should be done with caution or following a presacrifice by-pass procedure, and
      nine patients in Group III with PET quantitated CBFs below eligibility for
      carotid sacrifice, were not identified by EEG monitoring. Even when CBF falls
      below 25 ml/100 g/minute continuous EEG monitoring is insensitive to reduction in
      perfusion. Reliance upon EEG for detection of cerebral hypoperfusion in
      interventionl neuroradiological procedures will significantly underestimate
      ischaemic risk.

PMID- 20673391
TI  - [O-15]H2O Positron Emission Tomography Determination of Cerebral Blood Flow
      Reserve after Intravenous Acetazolamide during Balloon Test Occlusion of the
      Internal Carotid Artery.
AB  - SUMMARY: The purpose of this paper was to evaluate the effects of acetazolamide
      on cerebral blood flow (CBF) measured by [O-15]H2O positron emission tomography
      (PET) during balloon test occlusion (BTO) of the internal carotid artery (ICA).
      [O-15]H2O PET cerebral blood flow studies were completed in 20 patients
      undergoing BTO CBF determinations were obtained without carotid occlusion as a
      baseline, following balloon occlusion, and as a third scan with balloon occlusion
      after an intravenous acetazolamide bolus. The balloon was left deflated between
      scans, and was only inflated immediately before and during the 90 second period
      of time needed for CBF determination. Significance was determined at the P < 0.05
      level. Two of twenty studies were technical failures. Prior to acetazolamide
      there was a significant decrease in CBF (P < 0.0007) ipsilateral to the
      occlusion. After acetazolamide administration there was no statistically
      significant change in flow on the occluded side (P < 0.3047); however, there was
      a significant increase in cerebral blood flow (P < 0.0002) on the non-occluded
      side. In this patient population, there was no acetazolamide-induced CBF
      decompensation (steal) phenomenon or haemodynamically significant risk in CBF
      ipsilateral to the occlusion.

PMID- 20673392
TI  - Penetration Difference of n-Butyl2-Cyanoacrylate into the Nidus in the
      Embolisation of Brain Arteriovenous Malformation.
AB  - SUMMARY: Prediction of nidal penetration of the glue is difficult in the
      embolisation of brain arteriovenous malformations (AVM). We evaluated penetration
      differences of glue-lipiodol mixtures with and without tungsten powder for
      embolisation of brain AVM. Fifty eight injections during embolisation of brain
      AVM in 15 patients were evaluated. Glue contained lipiodol only (N=25), or
      lipiodol and tungsten powder (N=33). Glue concentration ranged from 20 to 80%.
      Injection was done at the pedicle (N=41) or nidus (N=17). Degree of penetration
      was rated as good, fair, or poor according to penetrated glue amount in the
      nidus. Penetration difference was compared in each injection at the pedicle or
      nidus. When the glue mixtures were injected at the pedicle, the glue-lipiodol
      mixture (GLM) penetrated into the nidus in eight of 16 injections (50%) and the
      glue-lipiodol-tungsten mixtures (GLTM) in 23 of 25 (92%). When glue was injected
      at the nidus, GLM was confined to the nidus in nine of nine injections (100%) and
      GLTM in seven of eight (88%). Penetration into the vein was noted in two of 25
      injections (8%) in GLM and six of 33 (18%) in GLTM. Penetration difference into
      the nidus between GLM and GLTM was statistically significant (p < 0.05) when the
      glue mixtures were injected at the pedicle. GLM and GLTM can be used effectively
      at the nidus. In contrast to GLM, GLTM can be used effectively at the pedicle.
      However, the risk of venous penetration seemed to be higher with GLTM than in
      GLM.

PMID- 20673393
TI  - Basilar artery fenestration aneurysms treated with guglielmi detachable coils.
AB  - SUMMARY: Four patients with basilar artery fenestration aneurysms at the vertebra
      basilar junction were admitted after subarachnoid haemorrhage. In two of them
      attempted surgery failed. Subsequently, all four were embolised with Guglielmi
      Detachable Coils (GDC), three of them in the acute phase. In one case the initial
      embolisation was incomplete, but follow-up angiography demonstrated spontaneous
      total occlusion. In another, partial reopening was treated with further
      embolisation. Three patients recovered completely after treatment. One patient
      still has deficits related to surgery of an accompanying aneurysm at the middle
      cerebral artery. He is clinically improving but still not back at work. In two
      cases the fenestration was combined with a hypoplastic upper vertebral artery on
      one side. A hypoplastic veretebral artery on one side may frequently be part of
      the developmental anomaly of basilar fenestration aneurysms. The anatomical
      configuration and location of these aneurysms is such that their true nature is
      sometimes difficult to disclose at cerebral angiography and is only realised
      during embolisation. Treatment with GDC coils seems superior to surgery in
      basilar artery fenestration aneurysms.

PMID- 20673394
TI  - Motor evoked potentials predicting early recovery from paraparesis after
      embolisation of a spinal dural arteriovenous fistula.
AB  - SUMMARY: Spinal dural arteriovenous malformation is an increasingly diagnosed
      cause of ischaemic myelopathy. Though routine intraoperative monitoring has been
      demonstrated to be of benefit in the endovascular treatment of these lesions, its
      predictive value has not been well documented. We present the case of an elderly
      woman with progressive spastic paraparesis who demonstrated marked improvement in
      limb muscle motor evoked potentials of the lower extremities immediately
      following endovascular occlusion of the lesion. The patient subsequently showed
      improvement in strength, sensation and sphincter control.

PMID- 20673395
TI  - De Novo Appearance of Three Cavernomas in an Infant with Dural AV Shunts. Case
      Report.
AB  - SUMMARY: Cavernomas of the brain and spinal cord are malformations which are
      generally considered congenital and often found in young adults. Although the
      distinction of a sporadic and a hereditary type is discussed, the natural history
      is still poorly understood. We present the unusual case of an infant first
      submitted to CT scan, MRI and MR-angiography at the age of three months,
      revealing multiple AV shunts of the superior sagittal and the sigmoid sinus, with
      a small pial supply. A second angiogram at the age of six months showed an
      additional parietal pial AVM. At this time, partial embolisation of the dural AV
      shunts was performed. At the age of three, the child was restudied by MRI and
      three formerly invisible cavernomas were detected.

PMID- 20673396
TI  - Aneurysm on a persisting primitive trigeminal artery occluded with guglielmi
      detachable coils.
AB  - SUMMARY: A persisting primitive trigeminal artery (PPTA) is present in 0.2 - 0.6%
      of all cerebral angiographies. 27 cases of PPTA aneurysms have been reported. We
      present a case with sixth cranial nerve palsy due to a non ruptured aneurysm on a
      persisting primitive trigeminal artery. The aneurysm was successfully occluded
      with Guglielmi Detachable Coils with preservation of the parent artery. The
      cranial nerve palsy resolved and recovery was uneventful.

PMID- 20673397
TI  - Letter to the editor. Early polymerisation of histoacryl mixed with lipiodol.

PMID- 20673398
TI  - Editorial. Ethics and research: applications in interventional neuroradiology.

PMID- 20673399
TI  - Origin of the perforating arteries of the interpeduncular fossa in relation to
      the termination of the basilar artery.
AB  - SUMMARY: We studied the perforating arteries of the interpeduncular fossa in 100
      human brains which had previously been embalmed and injected with coloured
      intravascular neoprene latex. Three groups of perforating arteries were observed:
      the short interpeduncular arteries, a group of very fine arteries which can
      originate on every artery in the interpeduncular fossa and are destined to the
      cerebral peduncles and the oculomotor nerves (III); the diencephalic arteries,
      larger in diameter, most of which supply the mamillary bodies; only a few of them
      (one or two) penetrate the diencephalic floor and reach the posterior limb of the
      internal capsule and the anterior and medial thalamus; the diencephalic arteries
      are either individual branches of the PI segment of the posterior cerebral
      arteries (PCA) or stem from the same segment of the PCA via a trunk common to the
      mesencephalic arteries; the latter supply the mesencephalic area medial to the
      pars reticularis of the black substance. Our study focusses on where the
      diencephalic and mesencephalic arteries originate, based on how both anterior
      longitudinal neural arteries merged into a basilar artery in the embryo. When
      merging was symmetrical, whether in the early stages or later, the origins are
      more or less equally distributed; however, when merging was asymmetrical, the
      great majority of the perforating diencephalic and mesencephalic arteries stem
      from the P1 segment on the side that merged earliest (cranially).

PMID- 20673400
TI  - Basilar tip aneurysms and basilar tip anatomy.
AB  - SUMMARY: Five hundred and eighty one cerebral aneurysms seen from 1986-1997 were
      reviewed. Fifty five basilar tip aneurysms were demonstrated. The analysis of the
      anatomic disposition of the distal basilar artery in 47 of them showed the
      prevalence of caudal fusion in 91% of cases. The fusion is either symmetrical or
      asymmetrical. The neck of the aneurysm is preferentially implanted on the caudal
      part of the fusion. Recognition of the distal basilar artery anatomy allows the
      origin and extent of the perforating branches territory arising from the PI
      segment to be predicted in each type of basilar tip disposition. The caudal
      variant supplies a small ipsilateral territory, whereas the cranial one often
      provides a bilateral supply. In the cranial arrangement one can observe
      interpeduncular anastomoses between the perforators across the midline prior to
      penetrating the mesencephalo-diencephalic structures. The risks involved in the
      sacrifice of the P1 segment can then be anticipated.

PMID- 20673401
TI  - Paediatric spinal arteriovenous malformations: angioarchitecture and endovascular
      treatment.
AB  - SUMMARY: This is a retrospective review of the clinical records and imaging of 14
      children with spinal arteriovenous malformations referred to the
      neurointerventional service at our institution. The lesions are categorized by
      anatomic location into subpial (5 cases), epidural (3 cases), and paraspinal (6
      cases). There were no dural arteriovenous fistulas in this group. The subpial
      lesions include both the intramedullary arteriovenous malformations (2 cases) and
      the perimedullary arteriovenous fistulas (3 cases). Two of the patients with
      perimedullary fistulas were first cousins and both had Rendu-Osler-Weber
      syndrome. The six paraspinallesions were vertebral-vertebral fistulas with five
      of these located at the first cervical metamere. Eleven cases (79%) were
      arteriovenous fistulas and three cases (21 %) were arteriovenous malformations
      with a nidus. There were nine (82%) high flow arteriovenous fistulae and two
      (18%) low flow arteriovenous fistulae. The ages range from seven months to 15
      years, with a mean age of seven years. There were nine males and five females.
      Clinical presentations included: bruit alone (6 patients), progressive scoliosis
      (1 patient), pain (2 patients), neurologic deficit (4 patients) and one case of
      Cobb's syndrome. Management included: no treatment (1 patient), endovascular
      embolisation (10 patients) and surgery (3 patients). Of the patients who
      underwent endovascular treatment all were treated from the arterial side. Two
      patients were treated by N-butyl cyanoacrylate (NBCA) alone, two with NBCA and
      coils, one with balloons alone, three with balloons and coils and two with coils
      alone. In the endovascular treatment group, nine fistulae were completely
      obliterated (all high flow fistulae) and one patient had partial treatment (a
      spinal cord arteriovenous malformation). There were no complications from
      endovascular treatment.

PMID- 20673402
TI  - Endovascular coil embolisation of metachronous mycotic aneurysms. Case
      presentation and review of technical and management issues.
AB  - SUMMARY: While receiving optimal antibiotic therapy for subacute bacterial
      endocarditis (SBE), a teenage girl with mild congenital mitral insufficiency
      presented with two separate episodes of subarachnoid haemorrhage from two rapidly
      evolving metachronous mycotic aneurysms within the vertebrobasilar circulation.
      Both aneurysms were successfully treated by endovascular coil embolisation with
      the GDC system. This permitted at the minimum, successful amelioration of the
      short term risk of rerupture of the aneurysms, and facilitated operative
      management of the patient's infected mitral valve. The case further illustrates
      the utility and effectiveness of endovascular therapy for managing not only the
      neurovascular sequelae of SBE, but also perhaps the enhanced ability to optimally
      manage the source of mycotic aneurysms. In addition, the potential limitations
      and risks of this therapeutic strategy are assessed.

PMID- 20673403
TI  - Multiple spinal perimedullary arteriovenous fistulae associated with the parkes
      weber syndrome. A case report.
AB  - SUMMARY: We present a rare case of multiple spinal perimedullary arteriovenous
      fistulae associated with the Parkes-Weber (PW) syndrome. A 31-year-old male known
      to have the PW syndrome involving the left leg since birth, presented with a 7
      month-history of progressive myelopathy of the lower extremities and dysfunction
      of the bladder and bowel. Myelography demonstrated dilated intradural vessels.
      Angiography demonstrated two distinct single hole perimedullary arteriovenous
      fistulae near the conus at two different metameres. They were supplied by the
      left posterior spinal artery. The patient was treated by transarterial
      embolisation using polyvinyl alcohol particles, which resulted in venous side
      occlusion of the fistulae. After the treatment, the patient developed transient
      worsening of the spasticity of the lower extremities, and was treated by
      heparinization. After heparinization, the patient partially recovered from the
      pre-embolisation status of his myelopathy. The follow-up angiogram one year after
      the embolisation demonstrated persistent obliteration of both fistulae. At long
      term follow-up, the patient can ambulate without assistance and work as a farmer.

PMID- 20673404
TI  - Mechanical intracranial embolectomy. A report of two cases.
AB  - SUMMARY: Cerebral ischaemia due to thrombo-embolic complications of intracranial
      endovascular therapy remains one of the more obvious hazards of this otherwise
      rather gentle treatment. In this connection the time factor is usually well
      controlled and the possibility to achieve a good result from thrombolysis are
      possibly better(7). To directly extract an embolus mechanically would be an
      attractive alternative. This has so far been hampered by the lack of suitable
      tools. The use of a microsnare intended for intravascular retrieval of foreign
      bodies like displaced coils or broken catheters shown here must further encourage
      development of specially designed "thrombectomy devices" for intracranial use.
      Such a tool may well have an impact on the treatment of noniatrogenic emboli as
      well.

PMID- 20673405
TI  - A pitfall of fibrinolysis. Aneurysms found after attempted fibrinolytic therapy
      of occluded arteries.
AB  - SUMMARY: Three patients with angiographically invisible aneurysms found after
      attempted fibrinolytic therapy are presented. One aneurysm bled during the
      procedure with a tragic result. All of aneurysms were located distal to the
      occluded arteries. Aneurysms were preexisting and invisible distal to the
      occluded artery, or they developed rapidly after the fibrinolysis. These
      aneurysms were at a risk for rupture during and after fibrinolytic therapy.

PMID- 20673406
TI  - Foramen magnum dural arteriovenous fistulae with repeated subarachnoid
      haemorrhage.
AB  - SUMMARY: We report a patient who had dural arteriovenous fistulae in the region
      of the foramen magnum with repeated subarachnoid haemorrhage. Magnetic resonance
      imaging revealed abnormal vascular structures on the right side of the medulla
      oblongata in an extra-axial portion. Angiographic findings showed that the lesion
      was supplied from the meningeal arteries and drained directly into the
      subarachnoid vein. There was venous dilatation. Embolisation was performed via
      the transarterial approach using a micro coil and liquid material. Three years
      after treatment, the patients' condition is good and follow-up angiograms
      confirmed the stability of the treatment outcome. While dural arteriovenous
      fistulae of the foramen magnum are rare, this malformation results in a high rate
      of bleeding and requires treatment.

PMID- 20673407
TI  - Letter to the Editor. Neck Plastic Intra-Aneurysmal GDC Embolisation with Double
      Protective Balloons. Method of Multiple Guiding Catheter Introduction.

PMID- 20673408
TI  - Letter to the Editor. Pre-operative Embolisation of the Inferior Petrosal Sinus:
      Is It Free of Risks?

PMID- 20673409
TI  - Editorial. The Issue of Carotid Stenting: the Impetus to Change our Practice of
      Interventional Neuroradiology?

PMID- 20673410
TI  - 1998 world Federation of interventional and therapeutic neuroradiology.
      Guidelines for fellowship training programmes in interventional neuroradiology.

PMID- 20673411
TI  - Errata corrige. Basilar tip aneurysms and basilar tip anatomy. Interventional
      neuroradiology 4: 121-125, 1998.

PMID- 20673412
TI  - Radiation dose and image quality in neuroangiography: effects of increased tube
      voltage, added x-ray filtration and antiscatter grid removal.
AB  - SUMMARY: During endovascular treatment the patient may be subject to fluoroscopy
      for long periods as well as multiple x-ray exposures. The radiation dose to the
      patient can be considerable, and cause local deterministic effects such as
      alopecia or even skin burn. The potential carcinogenic effects should also be
      noted, being especially important in the paediatric population. We measured
      radiation doses to patients and personnel during neuroendovascular procedures and
      diagnostic neuroangiography. We also tried to reduce the radiation dose to the
      patient utilising increased tube voltage, additional primary X-ray filtration and
      by removing the antiscatter grid in front of the image intensifier, employing air
      gap technique. We investigated radiation doses to patient and personnel during
      neuroangiographic procedures and optimized the examination technique with regard
      to radiation dose with maintained image quality. Radiation exposure to patients
      and personnel was measured with thermoluminescent dosimeters and permanently
      mounted KermaDoseArea-Product meters in front of the X-ray tubes during 13
      cerebral angiographies and six neuroendovascular procedures. We performed
      experiments with radiation dose measurements and evaluation of image quality with
      80 and 90 kV tube voltage during image acquisition and 75 and 85 kV during
      fluoroscopy, as well as with different primary X-ray filtration. Images from
      patient studies acquired with the original grid in front of the image intensifier
      were compared with images from patient studies acquired with the grid removed and
      air gap technique (30 cm). Images from patient studies acquired with the original
      examination technique were compared to images from patient studies acquired with
      increased x-ray tube voltage, increased x-ray filtering and with the antiscatter
      grid removed using an airgap as scatter reduction method. Radiation exposure to
      personnel was very low using standard protective devices. Measurable doses were
      recorded only on the hands and forehead of the neuroradiologist. Maximum entrance
      skin dose was about 1 Gy on the side of the patientspatient's forehead during an
      endovascular procedure. Increasing the tube voltage from 75 to 85 - 85 and 90 kV,
      exchanging the original 0.5 mm aluminium primary filtration for 0.2 mm copper and
      removing the antiscatter grid allowed us to reduce entrance skin dose to the
      patient by 70% with unchanged or slightly improved image quality.

PMID- 20673413
TI  - Pre-operative Angiography and Embolisation of Petroclival Meningiomas.
AB  - SUMMARY: We reviewed our experience of 15 patients with petroclival meningiomas
      who underwent pre-operative angiography, 11 of whom were embolised in the same
      session. We analysed our cases to evaluate the variations in vascular supply to
      these tumours, their potential for embolisation, and the techniques used for
      their devascularization; as well as associated MRl findings. The petroclival
      region is vascularised by the basal tentorial arcade. Petroclival meningiomas
      derive their blood supply from the ICA and ECA branches which form this network,
      and may also parasitize supply from the vertebrobasilar system. ICA
      (meningohypophyseal trunk) supply was present in all our patients, and 93% also
      had ECA contributions (basal tentorial branches of the middle and accessory
      meningeal arteries, the ascending pharyngeal artery, the artery of foramen
      rotundum and transmastoid branches of the occipital artery). 47% had pial supply
      from the vertebrobasilar system. The ECA supply was partly or completely
      embolised in each of the 11 patients, and the meningohypophyseal contribution in
      one; there were no complications. Pre-operative angiographic assessment of
      patients with petroclival meningiomas provides important information for
      determining the surgical approach, and when combined with embolisation may
      facilitate a more complete resection of these surgically challenging lesions.

PMID- 20673414
TI  - Combined transarterial and transvenous embolisation of jugulotympanic
      paragangliomas.
AB  - SUMMARY: Paragangliomas of the jugular region present a greater challenge to the
      surgeon than paragangliomas in other locations. Because of the vascular nature of
      the tumour, bleeding can be substantial not only from arterial inflow to the
      tumour, but also from venous bleeding, if not embolised prior to surgery. Six
      patients were treated with combined transarterial and transvenous embolisation
      followed by surgical resection. In each instance, the diagnosis of jugulotympanic
      paraganglioma was suspected based on MR features. Substantial reduction in loss
      of blood appears to result from the combined transarterial and transvenous
      embolisation approach.

PMID- 20673415
TI  - Pitfalls of GDC Embolisation of Intracranial Aneurysms.
AB  - SUMMARY: We present a critical analysis of the cerebral aneurysm GDC embolisation
      technique and its numerous possible pitfalls with the experience of 448 aneurysms
      in 401 patients performed during a seven year period at UCLA's Division of
      Interventional Neuroradiology. A "pitfall" is defined as any hidden or not easily
      recognized danger or difficulty. We review pitfalls related to micro
      catheterization, GDC coil delivery, complex vascular anatomy, post-embolisation
      management, and pre-existing patient's clinical condition. The possible
      associated technical and clinical complications include aneurysm rupture, parent
      artery occlusion, thrombo-embolic stroke, coil stretching/rupture, coil
      migration, incomplete embolisation or embolisation failure. Lastly we present a
      discussion of our experience and suggestions of how to avoid some of these
      pitfalls.

PMID- 20673416
TI  - Endovascular treatment of an intracranial dural arteriovenous fistula with spinal
      venous drainage. A case report.
AB  - SUMMARY: A case of type V intracranial dural arteriovenous fistula (DAVF) is
      reported because of its unusual rapidly progressive paraparesis, Despite this
      clinical presentation, the diagnosis of DAVF was made and precocious endovascular
      treatment was instituted, Angiographic normalization was obtained after
      embolisation and the patient significantly improved within the first weeks,
      although at the six month control MRI there still was a hyperintense signal of
      the cord in T2 weighted images, but less extensive than originally.

PMID- 20673417
TI  - Post-embolisation flow disturbances at the basilar tip triggering the development
      of an arterial aneurysm. A case report.
AB  - SUMMARY: We present the case of an ll-year-old boy with a large intracerebral and
      intraventricular haemorrhage due to rupture of a left temporal arteriovenous
      malformation. The child initially presented with severe headaches and meningism,
      right VIth nerve palsy, right hemianopsia, and expressive aphasia. After
      stabilization of his neurological status, the patient was embolised in two
      sessions with acrylic glue (Histoacryl(*)), obliterating nearly 90% of the nidus,
      the residual to be considered for gamma-knife radiosurgery. The first session of
      embolisation had been complicated, during retrieval of the microcatheter, by an
      erratic embolus of glue in the basilar artery. The child was kept for 24 hours
      under heparin anticoagulation in order to avoid any thrombosis, followed by
      aspirin. His neurological examination remained stable without worsening of his
      clinical condition. Further angiographic controls demonstrated the patency of the
      basilar artery itself with remodelling changes at the basilar tip, with
      preservation of the perforators in this region. Secondary dilatation of the
      basilar tip with development of an arterial aneurysm was noted three years after
      the accident, pointing to the importance of flow turbulence and vascular wall
      weakness in the development of an arterial aneurysm. The clinical follow-up of
      this patient is 3.5 years; his neurological status is stable with hemianopsia,
      mild dysphasia and memory difficulties. Further follow-up will be needed in order
      to determine the therapeutic requirement for the arterial aneurysm.

PMID- 20673418
TI  - Endovascular treatment of intracavernous carotid aneurysm with
      hyperprolactinaemia.
AB  - SUMMARY: A 42-year-old woman presented with headache, galactorrhoea, marked
      hyperprolactinemia and normal neurologic examination. CT, MR and MR-angiography
      showed an intracavernous carotid artery aneurysm with minimal displacement of the
      pituitary stalk. Treatment by embolisation using GDC coils allowed exclusion of
      the aneurysm. Galactorrhoea resolved and serum prolactin levels fell to normal
      after eight months. Followup MR showed absence of the aneurysm, although the
      discrete mass effect persisted, suggesting that hyperprolactinaemia was due to
      pulsatility.

PMID- 20673419
TI  - Letter to the editor. I have seen as a child.

PMID- 20673420
TI  - Letter to the Editor. Premature Polymerisation of Histoacryl mixed with Lipiodol.

PMID- 20673421
TI  - Letter to the editor. Experiments with lipiodol.

PMID- 20673422
TI  - Prognostic assessment in cerebral arteriovenous malformations.

PMID- 20673423
TI  - Percutaneous treatment of herniated lumbar disc by intradiscal oxygen-ozone
      injection.
AB  - SUMMARY: We report our experience of treating lumbar herniated disc by
      intradiscal injection of an oxygen-ozone mixture. Ozone (03, MW = 48) is a
      triatomic molecule, having antiviral, disinfectant and antiseptic properties.
      Several mechanisms of action have been proposed to explain the efficacy of the
      treatment: 1) analgesic action; 2) anti-inflammatory action; 3) oxidant action on
      the proteoglycan in the nucleus pulposus. We treated 93 patients (50 women, 43
      men) aged from 24 to 45 yrs (average age 38 yrs) from June 1996 to April 1998.
      All patients presented sciatica and/or low back pain, lasting two or more months;
      patients had in the mean time received both medical and physical therapy with
      mild or no benefit. Diagnostic tests in all patients included plain film x-ray,
      CT and/or MR at the level of the lumbar spine disclasing a herniated or protruded
      disc with nerve root or thecal sac compression. We divided patients to be treated
      in to two groups: the first one group included 35 patients already selected for
      surgery who presented herniated or protruded disc with radicular pain with
      associated neurological deficit (hypoesthesia and partial loss of reflex). Those
      patients had already had medical and physical therapy for two or more months and
      agreed to try the percutaneous treatment before surgery. CT or MR in this group
      demonstrated the presence of intraforaminal, extra or sub-ligamentary and
      sequestrated herniated disc. The second group included 58 patients with radicular
      pain but without neurological deficit; patients in this group had received
      medical and/or physical therapy for two or more months and CT showed the presence
      of a small subligamentary herniated or protruded disc. We considered the results
      according to the modified MacNab method. In the first group we had "failure" in
      all patients; in seven cases the symptoms improved for one month, but recurred
      later on. In the second group 45 patients had "success" showing complete clinical
      recovery within five to six days after treatment, all remained without symptoms
      up to six months or more of follow-up. The remaining 13 patients presented the
      same symptoms again within three months after a temporary clinical recovery. The
      goal of this study was to present this new technique that can also be compared
      with a previous study of different percutaneous treatment. Clinical and
      neuroradiological indications and the contraindications are well known, and must
      be followed to achieve good results and avoid complications.

PMID- 20673424
TI  - Spontaneous Resolution of a Ruptured Dissecting PICA Aneurysm. Report of Two
      Cases.
AB  - SUMMARY: Spontaneous dissecting aneurysms (SDAs) seldom involve the intradural
      vertebral artery VA, the posterior cerebral, basilar or postero inferior
      cerebellar arteries (PICAs), where they produce subarachnoid haemorrhage and/or
      ischaemia. These lesions may develop spontaneously or occasionally after minor
      trauma and occur in young people in whom there is no underlying abnormality to
      explain the appearance of the dissection in most cases. Spontaneous dissecting
      aneurysm of the PICA is rare and its natural history is not well understood.
      Surgery or endovascular treatment for PICA dissection remain controversial
      because they suggest vessel occlusion. Only in a few cases is the bypass between
      the occipital artery and the PICA possible with trapping of the dissected
      segment. Reinforcement of the arterial wall does not seem efficient and the
      surgical approach per se with sole exclusion of the aneurysm may be disastrous.
      We describe two cases of SDA of PICA that presented with subarachnoid haemorrhage
      (SAH), treated conservatively, with spontaneous cure of the lesions,
      angiographically confirmed at mid-time follow-up of five and four months. These
      favourable spontaneous thromboses, like 11 other similar case reported in the
      literature, did not show any rebleed. The possibility of a benign clinical course
      of this lesion exists; clinical and angiographic management of the patient before
      a decision for a aggressive treatment is proposed.

PMID- 20673425
TI  - Multiple Intracranial Arterial Aneurysms: A Congenital Metameric Disease? Review
      of 113 Consecutive Patients with 280 AA.
AB  - SUMMARY: We reviewed the angiographic study and clinical charts of 398
      consecutive cases of intracranial arterial aneurysms, involving adults and
      children in the last 11 years (1986-1997). Giant aneurysms, dissecting aneurysms,
      mycotic aneurysms, and fusiform aneurysm were excluded. From the 341 patients
      presenting so-called berry aneurysm disease, attention was paid to multiple
      aneurysm sub group. One hundred and thirteen cases were analysed and compared
      with a group of single AA (228 cases) from the same material. Three longitudinal
      embryological territories giving rise to cranial endothelial cells and media were
      used to regroup the aneurysm sites. Eighty four cases presented aneurysms in the
      rostral region (74%), 20 cases with aneurysms involving rostral and middle
      territories (18%), 1 case presented aneurysm involving the middle and caudal
      territories (0.9%),5 cases had aneurysms in the rostral and caudal territories
      (4.4%) and three cases presented aneurysm involving rostral, medial and caudal
      territories at the same time (2.7%). No multiple group was located in the middle
      or caudal territories alone. When several arterial territories were concerned
      they were adjacent in 95.6% of cases. Multiple AA could therefore result from
      mesodermal/neural crest stem cell or focal endothelial cell defect within one or
      two (usually consecutive) embryonic segments. Mirror lesions would correspond to
      bilateral symmetrical impairment in the same territory or involvement of a group
      of cells with bilateral distribution. AA may result from a constitutional
      vasculopathy, later expressed with focal overproduction of the arterial wall
      without remodelling correction. Secondary mutations and triggers are likely to be
      needed to lead to such AA production.

PMID- 20673426
TI  - Influence of temperature on embolisation with cyanoacrylate.
AB  - SUMMARY: We evaluated the influence of temperature on the viscosity of mixtures
      with different histoacrylllipiodol concentrations and on injection control, to
      test the radiological visualization of these mixtures. A viscosimeter was used to
      measure the viscosity of different histoacryl and lip iodol combinations at
      various temperatures. After introduction of these blends into the polyethylene
      tubes, their radiological densities were evaluated by means of CT and DSA.
      Viscosity was found to be directly proportional to the percentage of lipiodol and
      inversely proportional to the temperature. By digital subtraction, the mixtures
      were still visible when the percentage of histoacryl reached 90%. Warming
      histoacryl and lipiodol mixtures to a temperature that is close to 40 degrees C
      decreases the mixture's viscosity significantly and makes the injection easier to
      manage. Tantalum and tungsten powders do not necessarly have to be added to
      visualize mixtures containing less than 90% histoacryl.

PMID- 20673427
TI  - Endovascular management of a major vascular complication after orthognatic
      surgery.
AB  - SUMMARY: We describe the effective endovascular management of a severe
      haemorrhagic complication in a 24 year old man is reported which could not be
      controlled by surgical means. Major bleeding caused by bilateral injured internal
      maxillary arteries after orthognatic surgery occurred. Angiography proved to be
      efficient in exactly localizing the bleeding sites while endovascular occlusion
      ultimately stopped the bleeding in a life-threatening situation for the patient.

PMID- 20673428
TI  - Endovascular embolisation of a cerebral arteriovenous fistula with hereditary
      haemorrhagic telangiectasia. Case report and review of the literature.
AB  - SUMMARY: We report a case of cerebral arteriovenous fistula (AVF) associated with
      hereditary haemorrhagic telangiectasia (HHT). Although the patient had no
      symptoms from the cerebral AVF, the AVF was successfully embolised using a
      twostaged double provocative test. We reviewed the literature of HHT and have
      concluded that there are two types of cerebral arteriovenous communication in
      patients with HHT and endovascular embolisation is the most reasonable therapy
      for the fistula type from the standpoint of its angioarchitecture.

PMID- 20673429
TI  - Repositioning of displaced guglielmi detachable coils after endosaccular
      embolisation using a modification of the neck plastic technique. A technical
      note.
AB  - SUMMARY: After undergoing prior partial surgical clipping of an acutely ruptured
      internal carotid aneurysm, a 29-year-old woman was referred for endovascular
      treatment of the gradually enlarging aneurysm remnant. The aneurysm had a
      somewhat peculiar ellipsoid configuration due to placement of the clip, with the
      largest dimension measuring less than 4 mm, and the neck measuring approximately
      2 mm. Using the conventional endosaccular coil embolisation technique, two small
      electrolytically detachable coils were carefully folded into the aneurysm sac to
      produce excellent tight packing. However, immediately after detachment,a loop of
      the second coil inadvertently herniated out of the aneurysm into the center of
      the parent artery, exhibiting substantial pulse synchronous displacement. This
      created a potentially unstable situation for the remaining coils within the
      embolised aneurysm. To correct this problem we attempted to reposition the loop
      into the aneurysm using a modification of the previously described neck plastic
      technique. This technique succeeded without untoward complication. Although there
      are theoretical risks and limitations, the modified neck plastic technique may be
      useful in selective cases of inadvertent coil misplacement during endosaccular
      coil embolisation of aneurysms with the GDC system.

PMID- 20673430
TI  - Balloon migration into a giant carotid aneurysm after parent artery occlusion
      using detachable balloons.
AB  - SUMMARY: We treated a 70-year-old man with a giant paraophthalmic region aneurysm
      of the right internal carotid artery using the parent artery occlusion technique
      with three detachable balloons. Initially, the patient did well, but migration of
      the distal balloon into the aneurysm was detected seven months later. This report
      suggests that initial parent artery occlusion using balloons will not always
      induce permanent thrombosis of a large aneurysm, because the occlusion and
      thrombosis is strictly dependant on the position of the balloons that are used,
      and adjunct use of coils may be indicated.

PMID- 20673431
TI  - Accentuated Vasospasm during Treatment of an Acutely Ruptured Aneurysm with
      Electrolytically Detachable Coils: Coincidence or Causation?
AB  - SUMMARY: We report an unusual case of precipitous worsening of vasospasm
      associated with subarachnoid haemorrhage that developed during endosaccular coil
      embolisation of a ruptured posterior communicating aneurysm. The acutely
      worsening vasospasm occurred in the distal ipsilateral anterior circulation
      remote from the site of microcatheter manipulation, resulting in transient
      occlusion. Despite successful endovascular treatment of both the aneurysm and
      vasospasm, the patient continued to clinically decline and eventually died. This
      case raises important issues regarding the potential mechanisms and optimal
      therapeutic strategies for this complication, which are reviewed.

PMID- 20673433
TI  - Editorial comment. "Corrosion of tungsten spirals" by weill et Al.

PMID- 20673432
TI  - Letter. "Corrosion" of tungsten spirals. A disturbing finding.
AB  - SUMMARY: Very long-term (more than 30 months after treatment) skull plain films
      of patients treated with Mechanical Detachable Spirals "MDS" (tungsten) for
      intracranial aneurysm or dural fistula by venous approach, showed a decreasing
      level of radiopacity of the spirals suggesting that this material was resorbing
      with time. To date, all the aneurysms selectively treated with "MDS" which were
      followed-up by angiography more than 30 months after treatment (three cases)
      showed recanalization. The recanalization was proportional to degree of the
      "corrosion".

PMID- 20673434
TI  - From the literature. Carotid angioplasty. A two-year experience, results and
      complications.

PMID- 20673435
TI  - Thrombolytic therapy for cerebral embolism.
AB  - SUMMARY: We summarized our clinical experience of thrombolytic therapy for
      cerebral embolism to evaluate the relation between the prognosis and the
      occlusion site, and the role of pre-treatment CBF measurement for supratentorial
      cerebral embolism. 56 cases of thrombolysis were analyzed and results were
      compaired with conservative medical therapy group. For ICA embolism, we stopped
      thrombolysis in the early period because of its poor collateral circulation. MCA
      embolism seemed to be a good candidate for this treatment and results were
      significantly better than the conservative medical therapy group in good recovery
      rate, severe disablity rate and large size infarction rate. In basilar artery
      embolism, thrombolysis seemed to be the most effective treatment in spite of the
      high mortality rate. Pre-treatment CBF measurement was important and useful to
      estimate the severity of ischemia, and it could make it possible to avoid severe
      hemorrhagic complications.

PMID- 20673436
TI  - Intravascular ultrasound with percutaneous transluminal angioplasty for supra
      aortic arteries.
AB  - SUMMARY: One of the major complications during or after percutaneous transluminal
      angioplasty (PTA) is distal embolism. We performed intravascular ultrasound
      (IVUS) to assess the morphological characteristics of atheromatous plaques which
      caused stenosis of arteries. In 7 cases of ICA stenosis, IVUS demonstrated
      hyperechoic plaques which were considered to be fibrous. Mixed type of plaque was
      observed in one case of ICA stenosis and another one case of ICA stenosis had
      plaque which was hyperechoic with acoustic shadowing. In all cases of SCA
      stenosis, plaques were hypoechoic, indicating fatty plaque. Distal embolism
      occurred after PTA in the case of ICA stenosis which had a mixed type of plaque.
      It is important to evaluate plaque morphology to prevent distal embolism. PTA is
      considered to be contraindicated in cases of ICA stenosis having hypoechoic
      plaques or ulceration.

PMID- 20673437
TI  - Stenting of the extracranial carotid artery in a high-risk population.
AB  - SUMMARY: The results of nine patients with carotid stenosis in a high-risk
      surgical population that were treated by stent supported angioplasty are
      reported. There were eight males and one female between the ages of 53 to 74. A
      balloon expandable stent was deployed by a transfemoral approach. Technical
      success was achieved in all cases. There were no periprocedural complications.
      The mean % stenosis decreased from 84% to 5.2% after stenting. No arterial
      dissection was recorded and smooth contour of the vessel was demonstrated in all
      patients. We have observed long term patency for over 6 months in seven patients.
      Mean angiographic stenosis was 20% and 21% at 3 and 6 months, respectively
      (range, 5 to 32%). No further stenosis was recorded. Carotid stenting is an
      alternative strategy to carotid endoarterectomy (CEA) for high-risk patients, for
      whom the complications of CEA may exceed the potential benefits.

PMID- 20673438
TI  - Results and problems in percutaneous transluminal angioplasty for internal
      carotid artery stenosis.
AB  - SUMMARY: Percutaneous transluminal angioplasty (PTA) is currently performed as a
      therapeutic strategy for the management of the cervical carotid artery stenosis.
      In our clinic, PTA was performed successfully in all 24 patients initially.
      Restenosis was observed in 4 of 24 patients who received 3 to 6 month follow-up
      angiography. Repeated PTA was performed in 4 patients, 3 of whom were
      successfully treated, while severe wall dissection occurred in 1 patient.
      Furthermore, asymptomatic rerestenosis was noted in 1 of 4 patients who received
      repeated PTA. Dissection was noted in 5 of 28 procedures, which occurred more
      often in the patients with calcified or restenotic lesions. These results suggest
      that stenting or emergent surgery should be prepared in PTA of the carotid artery
      stenosis to avoid major complications, especially when the patients have
      calcified or restenotic lesions.

PMID- 20673439
TI  - PTA for Internal Carotid Artery Stenosis.
AB  - SUMMARY: Thirty-one lesions of internal carotid artery (ICA) stenosis were
      treated by percutaneous transluminal angioplasty (PTA). All the patients were
      males except two. There were 18 extracranial ICA stenosis and 13 intracranial ICA
      stenosis. Four patients were treated in acute stage and 27 were in chronic stage.
      In 27 patients in the chronic stage, clinical presentation was transient ischemic
      attack or reversible ischemic neurological deficits or minor completed stroke.
      Dilatation of any degree was observed in all patients except one in the chronic
      group. Good dilatation (stenosis ratio after PTA is less than 50%) was observed
      in 11 out of 13 intracranial lesions and in 10 out of 14 extracranial lesions.
      Restenosis was two out of 11 intracranial good dilated lesions and 6 out of 10
      good dilated extracraniallesions. No patients but one have experienced recurrent
      symptoms. Symptomatic complications occurred in only one patient who encountered
      arterial dissection during PTA resulting in severe hemiparesis. In four patients
      in the acute stage, dilatation of any degree was observed in two and good
      dilatation was seen in two. In conclusion, PTA for chronic ICA stenosis is an
      effective and safe technique. However, extracranial lesions tend to develop
      restenosis. Self-expandable stent will be one of the solutions for extracranial
      lesions. Major complications of PTA are distal embolism and arterial dissection.
      PTA for acute ICA stenosis is a challenging technique.

PMID- 20673440
TI  - Treatment of Restenosis after PTA for Internal Carotid Stenosis.
AB  - SUMMARY: Thirteen cases of restenosis occurred after percutaneous transluminal
      angioplasty (PTA) in 63 cases of internal carotid stenoses. They were treated by
      PTA or carotid endarterectomy. The patients were sufficiently informed of each
      treatment. Seven of them were initially treated by repeated PTA. The stenosis
      ratio improved from 82% to 30% after repeated PTA on average. However, one case
      in the PTA treated group resulted in restenosis and then carotid endarterectomy
      was performed. The other case also caused restenosis and was treated by PTA. Six
      cases were initially treated by carotid endarterectomy and all cases were
      successfully treated without difficulty. The success rate of the PTA was 2/7
      (29%) in restenosis cases. One case causing re-restenosis had severe
      calcification in the arterial wall. PTA was thought to be effective for the
      restenosis cases after initial PTA if the arterial calcification was not severe.

PMID- 20673441
TI  - Follow-up Study after Percutaneous Transluminal Cerebral Angioplasty.
AB  - SUMMARY: The purpose of this study was to assess the safety and efficacy of
      percutaneous transluminal cerebral balloon angioplasty (PTCBA) of extra- and
      intra-cranial arteries by investigating procedural outcome. Eighty
      haemodynamically significant extra- and intra-cranial lesions (% diameter
      stenosis > 70) in 74 clinically symptomatic patients were treated by elective and
      initial PTCBA between March 1991 and February 1996 and followed thereafter.
      Death, stroke including transient ischemia, surgery, or repeated angioplasty of
      restenosis or new lesions were regarded as cerebral events after the initial
      PTCBA. Crescendo ischaemic symptoms disappeared completely after clinically
      successful dilatation. The clinical success rate was 81% (65/80). Angiographic
      restenosis rate at 3 months was 22% (14/65). By life-table method, the
      death/stroke risk was 16% and death/stroke/surgery/repeated PTCBA risk was 49% at
      2 years following PTCBA, respectively. In conclusion, PTCBA successfully,
      decreased recurrent neurological symptoms and produced a favourable short-term
      outcome, whereas restenosis limited long-term benefit.

PMID- 20673442
TI  - Percutaneous transluminal angioplasty for intracranial atherosclerotic stenosis.
AB  - SUMMARY: Eleven patients with symptomatic intracranial atherosclerotic stenotic
      lesions underwent percutaneous transluminal angioplasty (PTA). Seven patients had
      stenosis in M1 segment of the middle cerebral artery (MCA), two in the cavernous
      internal carotid artery, one in M2 segment of the MCA and one in the P2 segment
      of the posterior cerebral artery. Initial successful dilatation (less than 50%
      residual stenosis) was obtained in nine patients (81.8%). Permanent neurological
      deficit related to PTA was seen in one patient and transient symptoms were
      observed in two. Re-stenosis was revealed in two cases (18.2%) in the early
      followup period. All patients with successful dilatation and without re-stenosis
      never had TIA or stroke after PTA. Intracranial PTA is an effective procedure,
      but several problems remain to be solved.

PMID- 20673443
TI  - Percutaneous Transluminal Angioplasty for Atherosclerotic Stenosis of the
      Intracranial Cerebral Arteries. Special reference to the device for reducing the
      complications drawn from the analysis of our complicated cases.
AB  - SUMMARY: Percutaneous transluminal angioplasty (PTA) was carried out 43 times for
      40 lesions in 38 cases of atheroscrelotic stenosis of the intracranial or skull
      base cerebral arteries. The stenotic lesions involved the middle cerebral artery
      in 15 cases, the basilar artery in seven cases, the internal carotid artery
      (petrous-supraclinoid portion) in 14 cases, and the intracranial vertebral artery
      in four cases. Nearly all cases were symptomatic, such as TIA or stroke, and the
      degree of stenosis ranged from 70 to 99 percent, with a mean of 80 percent. PTA
      was performed using a STEALTH balloon angioplasty catheter. In these trials, PTA
      was successfully performed (as indicated by a residual stenosis under 50%) 36
      times. The initial success rate was 84% and stenosis was reduced from 80% to 25%.
      Clinical follow-up was performed from 3 to 62 months with a mean of 40 months.
      During this period, death due to myocardial infarction or pneumonia occurred in
      four cases, stroke related to previous PTA occurred in one case (due to re
      stenosis) and stroke unrelated to previous PTA occurred in two cases.
      Angiographic follow-up was performed in 30 cases after 36 successful PTA
      procedures. Re-stenosis was seen in 20% of the cases, symptomatic complication
      occurred in 7%, and asymptomatic complications occurred in 7% of the cases. There
      was no mortality in this series. From analysis of complicated cases, there are
      several characteristic findings on the stenotic lesion. These are the stenotic
      lesions that located near the bifurcation, involving long segment, or showing
      irregular shape which is including ulcer or dissection. It is important to keep a
      fundamental and safe technique to reduce the complication. And besides, it is
      very important to keep the strict indication and to avoid the high-risk patient
      from a morphological point of view.

PMID- 20673444
TI  - Preoperative embolization for meningioma using lipiodol.
AB  - SUMMARY: Four patient (3 males, 1 female) with meningioma treated by preoperative
      embolization using lipiodol since January 1997 were included in this study.
      Almost the same procedure was performed on them; superselective catheterization
      into feeders from the external carotid artery, slow infusion of lipiodol, and
      proximal occlusion with liquid coils. Duration between embolization and direct
      surgery varied (5-13 days). Three meningiomas resected 5 days after the
      embolization were successful but one resected after 13 days needed transfusion.
      Post operative complications were seen in two patients, one is lockjaw due to
      ischaemia of the temporal muscles, and the other is transient dilatation of
      perifocal oedema. The ischaemic effect and safety of lipiodol as embolic material
      are discussed.

PMID- 20673445
TI  - Intra-aneurysmal Embolization for the Treatment of Cerebral Aneurysms Using
      Detachable Coils.
AB  - SUMMARY: From October 1993 to February 1998, intraaneurysmal embolization by
      endovascular treatment with detachable coils was performed for 41 cases of
      cerebral aneurysm. As a detachable coil, interlocking detachable coils (IDC) were
      used in the initial 15 cases and Guglielmi detachable coils (GDC) were used in
      the subsequent 26 cases. As for 15 cases treated with IDC, complete occlusion was
      performed in 9 cases, subtotal occlusion in 4 cases and partial occlusion in 2
      cases. In one of the partial occluded cases, a coil compaction occurred 6 months
      after embolization. Distal emboli were recognized on CT after embolization in 3
      cases, however, only one case was symptomatic. Intra-operative bleeding occurred
      in one case, but no obvious hemorrhage after coil embolization in any case. As
      for 26 cases treated with GDC, complete occlusion was performed in 18 cases,
      subtotal occlusion in 8 cases. In one case of basilar-tip aneurysm, a mild coil
      compaction occurred 6 months after embolization. Distal emboli were recognized on
      CT after embolization in 3 cases, however, only one case was symptomatic (minor
      stroke). No intra-operative bleeding and no obvious hemorrhage after coil
      embolization occurred in any case. From our experiences, treatment for poor-grade
      ruptured aneurysm is still difficult, but intraaneurysmal embolization for
      cerebral aneurysms using detachable coils is possible and a useful alternative,
      especially for surgically difficult aneurysms. The results of treatment of
      aneurysm with GDC are much better than those with IDC, so the indications for
      intra-aneurysmal embolization with GDC might increase in the future.

PMID- 20673446
TI  - Clinical Results and Problems in Embolization for Intracranial Aneurysms using
      Electrically Detachable Coils.
AB  - SUMMARY: Nineteen patients with intracranial aneurysm were treated using
      electrically detachable coils (GDC or IEDC) and angiographic results and
      complications were assessed. In 18 aneurysms treated by endosaccular occlusion,
      11 (61%), 3 (17%) and 4 (22%) resulted in complete occlusion, neck remnant and
      dome filling, respectively. Neither haemorrhagic nor thromboembolic complications
      occurred in 19 patients. Embolization using electrically detachable coils seemed
      to be a safe and useful procedure without complications, but we should give
      attention to avoiding complications and incomplete occlusion in particular in a
      case of 1) wide-necked, 2) small (< 3 mm) or 3) complex- shaped aneurysms.

PMID- 20673447
TI  - Coil embolization for intracranial aneurysm by direct puncture of the carotid
      artery in elderly patients.
AB  - SUMMARY: Seven aneurysms in elderly patients (average 78 year-old) were treated
      by intra-aneurysmal coil embolization. The 19 gage elastic needle or 4.0Fr.
      sheath introducer was placed into the carotid artery, and 3.0Fr. microcatheter
      was advanced into the aneurysm. An operative difficulty to approach to the
      aneurysm due to arteriosclerosis was ameliorated by this method. Mobility related
      to this procedure was a local hematoma at the puncture site in one case.

PMID- 20673448
TI  - Evaluation of Intra-aneurysmal Blood Flow: Investigation of the Flow in
      Experimental Aneurysms.
AB  - SUMMARY: We evaluated the flow in experimental pig aneurysms using a high speed
      video system with tracer particles and digital subtraction angiography (DSA). We
      found that flow velocity in experimental aneurysms was fast on the inflow of
      aneurysms. There was a certain correlation between mean transit time (MTT) and
      velocity in experimental aneurysms. Therefore, the differences of flow velocity
      in aneurysms will be detected using DSA. The flow in aneurysms was much changed
      by platinum coil embolization.

PMID- 20673449
TI  - Endosaccular embolization for internal carotid artery aneurysms at the c3
      portion.
AB  - SUMMARY: Direct surgery for the aneurysms at the C3 portion of the internal
      carotid artery (ICA) requires relatively complicated procedures. We present three
      patients with this aneurysm who underwent endovascular embolization. The
      remodelling technique was utilized in two of these patients with unruptured
      aneurysms. Sufficient obliteration was achieved in every case. Endovascular
      embolization may be an important alternative for ICA C3 aneurysms.

PMID- 20673450
TI  - A case of partially thrombosed giant basilar aneurysm successfully treated by
      coil embolization followed by proximal clipping.
AB  - SUMMARY: A case of unclippable partially thrombosed giant basilar artery (BA)
      aneurysm was treated successfully by intra-aneurysmal GDC embolization followed
      by proximal BA occlusion. Balloon occlusion test of the BA showed a good
      opacification of the aneurysm angiographically through plentiful collateral flow
      from anterior circulation. This combination may prevent coil compaction and will
      promote intra-aneurysmal thrombosis.

PMID- 20673451
TI  - Surgery of a large paraclinoid aneurysm with the support of coil embolization.
AB  - SUMMARY: An attempt was made to clip the neck of a large paraclinoid aneurysm
      with the support of a balloon catheter, using a trapping-evacuation technique.
      The clip applied to the neck slipped off because of blood pressure through the
      posterior communicating artery which arose from the dome of the aneurysm.
      Therefore, using portable digital subtraction angiography (DSA) equipment, we
      placed interlocking detachable coils (IDCs) in the aneurysm for the purpose of
      reducing the intraaneurysmal pressure. Although the aneurysm was eventually
      trapped with two clips, this case indicates the supportive role of intravascular
      intervention in aneurysmal surgery when clipping an aneurysm or immediately after
      clip failure.

PMID- 20673452
TI  - Embolization of Ruptured Cerebral Aneurysms with GDC in Acute Stage.
AB  - SUMMARY: 21 cases of 22 ruptured cerebral aneurysms were treated in acute stage
      with Guglielmi detachable coils and the outcome was assesed. GDCs were placed
      intra-aneurysm for intra-aneurysmal occlusion. CASES: age 42-80 (mean; 59) y.o.,
      7 male and 14 female; 4, 6, 8 and 3 patients were categorized (Hunt and Hess) as
      grades 1, 2, 3 and 4 respectively. GDC embolization was performed within 24 hours
      of primary hemorrhage in 11 patients, within 2 to 3 days in 4 patients and 5 to
      19 days in 6 patients. The occlusion rate was 100% in 7 ANs, more than 75% in 9
      ANs and less than 75% in 6 ANs. There were 7 cases of complications, two coil
      deposits, one embolism and 4 reruptures.

PMID- 20673453
TI  - Six cases of ruptured aneurysm, treated with cellulose acetate polymer.
AB  - SUMMARY: We review 6 cases of ruptured aneurysm which were elderly, poor-grade
      SAH or requiring high-risk surgery treated with Cellulose Acetate Polymer (CAP).
      A 76-year-old female with A-com aneurysm was comatose. Heart failure was her
      complication (case 1). An 81-year-old female with A-com aneurysm was semicomatose
      (case 2). An 89-year-old female with MCA aneurysm was semicomatose and had right
      hemiplegia (case 3). An 88-year-old female with MCA aneurysm was comatose (case
      4). A 55-year-old male with IC-PC aneurysm had a small intracerebral hematoma and
      was semicomatose (case 5). A 52-year-old female with IC-Ach aneurysm was
      somnolent (case 6). All cases had no rebleeding after embolization. CAP
      embolization was complete in all cases but case 1. Case 4 died from primary brain
      damage on the day 7. Three cases stayed in a severely disabled state and died
      after 3 months (case 1), 2 months (case 2) and 4 months (case 3) from onset
      respectively. Case 5 remains in a moderately disabled state after 2 years. Case 6
      had a anterior choroidal artery which was hard to spare on aneurysmal clipping.
      She is free from neurological deficits after CAP embolization. Angiography after
      2 years demonstrated complete obstruction of the aneurysm. CAP is good for cases
      which are elderly, poorgrade SAH or difficult to treat with surgery. CAP
      embolization has some advantages over GDC coil obstruction for aneurysm
      treatment.

PMID- 20673454
TI  - Spontaneous dissecting pseudoaneurysm of the extracranial internal carotid
      artery: endovascular treatment with a palmaz stent.
AB  - SUMMARY: This case illustrates the usefulness of an endovascular stent to treat a
      pseudoaneurysm of the cervical internal carotid artery. A 46-year-old male
      patient presented with a spontaneous dissection of the cervical internal carotid
      artery. After failing conservative therapy, he was treated by endovascular
      placement of a Palmaz stent at level of the pseudoaneurysm and dissection.
      Immediate obliteration of pseudoaneurysm was achieved, and patency of the
      internal carotid artery was maintained. The patient sustained no neurological
      complications and the stenosis of treated carotid artery did not occur during the
      6-month follow-up period. For internal carotid artery dissection, stent placement
      seems to be a reasonable therapeutic alternative to direct surgery.

PMID- 20673455
TI  - Vein-loaded stent system to occlude wide-necked aneurysms.
AB  - SUMMARY: We devised a vein-loaded stent system to immediately close the
      aneurysmal orifice without interrupting the parent arterial flow. Ten
      experimental widenecked aneurysms located on canine common carotid arteries were
      treated with the implantation of a newly modified vein-loaded stent system. After
      deploying the stent, half of them were managed under administration of 50 mg of
      ticlopidine hydrochloride per day and the other half followed up without any
      anticoagulation therapy. Immediately after the stent placement, all aneurysms
      were completely obliterated with patency of the parent artery in the successfully
      implanted vessels in both groups. Follow-up angiography one week later disclosed
      complete occlusion of the aneurysm with patency of the parent artery in 67% (2/3)
      of the group with ticlopidine, while none of the group without drugs showed
      patency of the parent artery. The rate of patency of the parent artery was found
      to be improved by administration of ticlopidine, but was still lower than that of
      a conventional stent. Further modifications will be needed before clinical use.

PMID- 20673456
TI  - Endovascular treatment of vein of galen aneurysmal malformations.
AB  - SUMMARY: We report two cases of vein of Galen aneurysmal dilatation (VGAD) and
      four cases of vein of Galen aneurysmal malformation (VGAM) with special reference
      to clinical features and therapeutic indications of endovascular treatment. A
      case with VGAD was treated by radiosurgery in 1985 with no amelioration to the
      patient. A case of choroidal type VGAM underwent an operation in 1987, but died
      of massive hemorrhage 2 years later. The other case of VGAD has been followed-up
      conservatively. The remaining cases of VGAM (two choroidal type and one mural
      type) were treated by endovascular treatment. The two cases of choroidal type
      were successfully embolized but died of systemic complications, and the only case
      of mural type was cured.

PMID- 20673457
TI  - The strategy of dural arteriovenous fistula with isolated sinus.
AB  - SUMMARY: We treated 7 cases of dural arteriovenous fistulas (dAVF) with isolated
      sinus by transvenous direct embolization. The fistulas located in the transverse
      sigmoid sinus in 5 cases, superior sagittal sinus in 1 case and transverse
      sigmoid and superior sagittal sinus in 1 case. The initial symptoms were
      generalized convulsion in 2 cases, disturbed consciousness in 1 case, tinnitus in
      2 cases and transient ischemic attack in 2 cases. We performed sinus packing with
      coils in all cases following transarterial embolization. All patients improved
      neurologically after the treatments and AVFs completely disappeared in all cases.

PMID- 20673458
TI  - Embolization of cerebral arteriovenous malformations with cellulose acetate
      polymer. Histological study of the resected specimens.
AB  - SUMMARY: To test the usefulness of a cellulose acetate polymer(CAP) solution for
      brain arteriovenous malformations (AVMs), we analyzed the clinical and
      histological results of patients with AVMs embolized using CAP solution. We
      reviewed the cases of six patients with cerebral AVMs treated by embolization
      prior to surgical resection. We used two types of CAP solutions, CAP-M and CAP-L,
      which are mixtures of 250 mg of solid CAP and 1800 or 2250 mg of bismuth trioxide
      dissolved in 5.5 or 7.0 ml of dimethyl sulfoxide, respectively. All patients
      underwent surgical resection 1 to 37 days after the embolization procedure.
      Resected specimens were fixed in formalin and stained for light microscopic
      examination. Eighteen feeding vessels were embolized. The reduction rate of the
      nidus volume was between 20% and nearly 100%. Mild ischemic deficits occurred in
      one patients but there were no hemorrhagic complications related to the
      embolization procedures. All AVMs were completely resected by surgery. Direct
      inspection at surgery revealed that there was no apparent swelling or hematomas
      in the normal brain areas adjacent to the nidus, and the AVMs were soft enough to
      be easily retracted. The histological examinations disclosed no or mild
      inflammatory reactions within two weeks after embolization. The internal elastic
      lamina was preserved in every case. Recanalization of embolized vessels was not
      observed until 37 days after embolization. CAP solution is a safe and useful
      embolic agent for brain AVMs. Further study is needed to resolve the issue of
      recanalization.

PMID- 20673459
TI  - Embolization of cerebral arteriovenous malformations to enhance the success of
      subsequent radiosurgery.
AB  - SUMMARY: We studied angiographic changes in embolized arteriovenous malformations
      (AVMs) by comparing pre- and postembolization angiograms and angiograms preceding
      radiosurgery. This study sought factors determining the usefulness of
      embolization as a pretreatment to enhance the success of subsequent radiosurgery.
      Thirty patients with cerebral AVMs treated in this manner over 4 years were
      studied. In these cases AVMs were embolized with cyanoacrylate and were treated
      with Gamma-knife radiosurgery. The mean size of the AVM nidus was reduced by a
      fraction of seven following embolization. The subsequent angiogram for planning
      radiosurgery showed further nidus reduction in 10 AVMs, no change in 12, and
      regrowth in 8. In all size-reduction cases the nidus was sufficiently packed, and
      2 AVMs had thrombosed completely before radiosurgery. All the regrowing AVMs were
      of diffuse type; 6 were associated with already-developed leptomeningeal
      channels, and the remaining 3 were fed by newly sprouted meningeal feeders. Five
      AVMs disappeared following radiosurgery, all representing size-reduction or
      nochange cases. Analysis of cases with regrowth showed increased risk of that
      event with feeder occlusion of a multi-axially supplied AVM, lack of reduction of
      shunt flow, or remaining meningeal feeders. On the other hand, when embolization
      as pretreatment prior to radiosurgery succeeds in producing a small, compacted,
      plexiform nidus with slow shunt flow, it furthers the likelihood of successful
      radiosurgery. Nidus embolization and occlusion of fistulous and meningeal feeders
      are mandatory, while proximal feeder occlusion and use of embolic materials which
      risk recanalization should be avoided to prevent nidus regrowth.

PMID- 20673460
TI  - Embolization of posterior circulation aneurysms with detachable coils.
AB  - SUMMARY: We evaluated the usefulness of endovascular treatment of posterior
      circulation aneurysms with GDCs and IDCs. Five cases were treated with IDCs, and
      15 cases were treated with GDCs. In this study, 8 aneurysms were identified at
      the basilar bifurcation, 3 at the PI segment of the posterior cerebral artery, 1
      at the origin of the superior cerebellar artery, 2 at the vertebrobasilar
      junction, 1 at the origin of the posterior inferior cerebellar artery, 1 at the
      distal anterior inferior cerebellar artery, and 4 dissecting aneurysms at the
      vertebral artery. Thirteen of the aneurysms were small (< 12 mm), 5 were large
      (13-24 mm), and 2 were giant (> 25 mm). Of the 20 patients, 14 patients returned
      to their previous occupation. Patients with permanent deficits included 2
      patients with infarction caused by thromboembolic complications during the
      embolization procedure, and 2 with infarction caused by vasospasm. There were 2
      deaths. The outcomes of the patients seemed favorable. However, long-term
      followup is necessary to determine the usefulness of detachable coils.

PMID- 20673461
TI  - Endovascular treatment of excessive spasticity from spinal cord injury. A case
      report.
AB  - SUMMARY: We report a new treatment for excessive spasticity using an endovascular
      technique. A 52-year-old woman with intractable spasticity of the hip joints and
      abdominal muscles was treated with an injection of 70% alcohol into Adamkiewicz's
      artery, which destroyed the spinal cord fed by Adamkiewicz's artery and cut the
      reflex arcs of excessive spasticity. Immediately after the treatment a
      significant change was noticed in muscle tonicity of the lower extremities, and
      intractable spasticity disappeared. Skin necrosis and muscle damage occurred
      because of the alcohol that leaked into the muscle branch of the subcostal
      artery. However, these complications could be treated by simple necrotomy. No
      recurrence was observed during the follow-up period. We believe this endovascular
      treatment will become a new strategy for excessive spasticity arising from spinal
      cord injury.

PMID- 20673462
TI  - The efficacy of endovascular surgery for treatment of giant aneurysms with
      special reference to coil embolization for endosaccular occlusion.
AB  - SUMMARY: We assessed the long-term follow-up results of platinum coil
      embolization and aneurysmography (ARG) with endovascular surgery for giant
      aneurysms. 24 cases of giant aneurysms were treated over a period of seven years.
      In the present study, the 16 of these for which surgical clipping was impossible
      so that only endovascular surgery was employed were investigated in detail. In 10
      cases the cavernous sinus area was involved, in two each the tip of the basilar
      artery, and the bifurcation of the ophthalmic artery, and in one each the
      extracranial internal carotid and the vertebral artery. Since conventional
      angiography did not allow the position and size of the neck of 10 cavernous sinus
      aneurysms to be identified, making treatment decisions difficult, we applied the
      ARG developed by the senior author. Prior to treatment, balloon test occlusion of
      the parent arteries was performed. In all 10 cavernous sinus cases, ARG
      successfully revealed the morphology of the aneurysm. A small neck was diagnosed
      for seven of the aneurysms of the cavernous sinus and all those located at the
      basilar and ophthalmic arteries, making a total of 11, and for these endosaccular
      embolization was carried out. In the other 5 cases, proximal occlusion using Gold
      valve balloons was performed. Under ARG, embolization of the aneurysms could be
      safely accomplished with platinum coils, without dislocation of the coils into
      the parent arteries in all cases. In four out of 10 cases, re-opening of the
      aneurysms occurred after 2 months or longer, so that re-embolization was
      required. Regarding complications, transient monoparesis of the upper extremity
      was encountered in one case. After angiographic and MRA follow-up of 1-36 months
      (average, 13.8 months), 4 of 10 cases demonstrated complete occlusion, and 5
      displayed an 80-90% reduction in blood flow. In only one case, involving a
      basilar tip aneurysm, was the treatment unsuccessful in preventing eventual
      rupture and death. In cases where the morphology of the aneurysm is unclear, ARG
      can be considered indispensable for determining the treatment modality and safe
      performance of localized embolization of the neck by endovascular surgery.
      However, since coils used for embolization of giant aneurysms may move or become
      compacted, re-opening can occur so that applications may be limited, especially
      with terminal type lesions with intraluminal thrombus, and the necessity for long
      term follow-up must be emphasized.

PMID- 20673463
TI  - Intravascular treatment for cerebral aneurysms.
AB  - SUMMARY: We have treated 142 aneurysms with intrasaccular or parent artery
      occlusions. Selective intrasaccular occlusions were attempted on 109 cases. Total
      or subtotal saccular occlusion was achieved in 93 of 96 cases. lntrasaccular
      occlusion could not be achieved in 13 cases because of various reasons such as
      wide neck, branching from aneurysmal dome, difficult to catheterize, and aneurysm
      too small. Parent artery occlusion was attempted on 33 cases. Twenty-five
      patients had giant aneurysms of the internal carotid artery (ICA) at the
      cavernous portion. The rest of this group had dissecting or fusiform aneurysms of
      the vertebral artery. Parent artery occlusion was achieved in 30 cases with six
      ischemic symptoms. High percentage of occlusion rate and low morbidity and
      mortality for metallic coil embolization prove the efficacy of this endovascular
      treatment.

PMID- 20673464
TI  - Surgical management of cerebral aneurysms in comparison with endovascular
      treatment.
AB  - SUMMARY: We report our surgical results of 92 intrabasal (below the ophthalmic
      segment) carotid aneurysms and 16 basilar aneurysms after the era of skull base
      surgery. These lesions were the most difficult location for neck clipping of
      aneurysms. Mortality, surgery associated mortality and morbidity of intra basal
      carotid aneurysm surgery were 2.2%, 0% and 9.7% respectively. Mortality and
      morbidity of basilar ameurysm surgery were 0% and 6.2% respectively. Although
      endovascular treatment of cerebral aneurysms with detachable coils is premising
      treatment due to its convenience and less invasiveness, results of this treatment
      must be superior to the results of microsurgery for it to become a widely
      accepted therapy.

PMID- 20673465
TI  - Treatment of cerebral aneurysms: surgical, endovascular or combined intervention.
AB  - SUMMARY: A retrospective study of 437 cases of cerebral aneurysms over a 4 year
      period is reported. Surgical clipping was performed in 322 cases (254 ruptured
      and 68 incidental aneurysms) and endovascular embolization was done in 50 cases
      (26 ruptured and 24 incidental aneurysms). No intervention (either surgical or
      endovascular) was performed in 65 patients. In the direct surgical treatment
      group, mortality was 1.5% in incidental and 9.8% in ruptured aneurysms and good
      recovery was seen in 98.5% and 74.8% cases respectively. In the endovascular
      intervention group, results were poor due to the severity of their neurological
      grading and older age. Mortality was 42.3% in ruptured and 4.2% in incidental
      aneurysms. Six out of 26 ruptured and 11 out 24 incidental aneurysm patients had
      complications in the endovascular treatment group. We have discussed the results
      and indications for both modes of treatment in our study.

PMID- 20673466
TI  - Coil Embolization of Cerebral Aneurysms. Experience with IDC and GDC.
AB  - SUMMARY: Coil embolization was performed in 86 cerebral aneurysm patients using
      two types of detachable platinum coils, IDC (Interlocking detachable coil) and
      GDC (Guglielmi electrical detachable coil). Results of IDC and GDC were compared.
      The occlusion rate of the aneurysm sac was similar. Coil compaction occurred
      frequent and early in cases with GDC. As clinical outcome, 94% of the patients in
      both group obtained good results. No bleeding or rebleeding occurred in the
      follow-up with IDC or GDC.

PMID- 20673467
TI  - Embolism in the superior cerebellar artery following coil embolization of basilar
      tip aneurysms: anatomy and hemodynamics.
AB  - SUMMARY: We aimed to identify anatomic factors favoring intra-aneurysmal clot
      embolization complicating coil embolization of basilar tip aneurysms. Thirty
      basilar tip aneurysm cases were classified angiographically into three types
      according to branching pattern of the superior cerebellar artery (SCA) and coil
      embolization complications were analyzed. The SCA may arise from the basilar
      artery (BA) just proximal to the origin of the posterior cerebral artery (PCA),
      initially coursing at an angle (more than 60 degrees ) relative to the BA, (type
      A). Alternatively the SCA may originate directly from the PCA at a sharp angle
      less than 30 degrees relative to the BA (type C). Type B includes patterns
      intermediate between types A and C. Behavior of particles chosen to simulate
      intra-aneurysmal clots was also observed in a plastic tube model with pulsatile
      water flow simulating configurations A and C. Type C branching was seen in 35%
      (21/60) of SCA, being dominant on the left side and associated with large
      aneurysms and broad necks. All 3 of 24 coil embolization patients with ischemic
      complications in the SCA territory had large aneurysms and type C SCA branching,
      2 aneurysms having broad necks. in the plastic model embolized "clots" more
      frequently lodged in type C than in type A SCA. "Clots" close to the orifice
      migrated more easily than those in the dome of the plastic aneurysm. Large
      basilar tip aneurysms with broad necks carry a risk of intra-aneurysmal clot
      migration into the SCA, during and after the embolization, especially in type C
      configurations, because pulsatile blood flow in the basilar artery may disperse
      clots between the coils and carry them into the sharply angulated SCA. Avoiding
      this complication requires meticulous coil packing to interrupt inflow into the
      aneurysm as well as appropriate anti-coagulation therapy.

PMID- 20673468
TI  - An in vitro study to define the term "dense packing" of aneurysms with detachable
      coils, liquid embolic material and their combination.
AB  - SUMMARY: The purpose of this study was to define the terms minimal and maximal
      "dense packing" of a given cavity with platinum coils and liquid material
      (cellulose acetate polymer; CAP) using precise in vitro volumetric methods. Tests
      were performed using a simple in vitro aneurysm model, precisely measured in
      volume and thereafter filled with platinum coils and/or CAP. The volume of the
      aneurysmal cavity was measured with a very precise special micropump. The volume
      of each platinum coil (GDC) was also calculated. Minimal dense packing was
      defined as the point where there was angiographic evidence of complete filling of
      the cavity and exclusion from the parent lumen of the aneurysm. Maximal dense
      packing was defined as the point where introduction of additional coils resulted
      in their protrusion into the parent artery. At minimal dense packing the ratio of
      aneurysm volume to coil volume ranged from 25.97% to 32.50%. At maximal dense
      packing the ratio ranged from 29.55% to 36.16%. The volumetric ratio ofminimal
      and maximal dense packing obtained was lower than we had expected. The volumetric
      ratio with CAP was 106.08% and 126.08% and the ratio obtained by the combined use
      of coils and CAP ranged from 103.78% to 140.2%. When the volumetric ratio of the
      packing is much lower than the ratio of dense packing by rough estimate, we
      should expect coil compaction and careful follow-up should be done. Liquid
      material filled the lumen more densely and the additional use of liquid may be
      useful to prevent coil compaction.

PMID- 20673469
TI  - Measurement of volume ratio to predict coil compaction, on aneurysmal
      embolization.
AB  - SUMMARY: The relationship between volume embolization ratio and coil compaction
      on the intracranial aneurysms occluded using Guglielmi detachable coils (GDCs)
      was determined. From March 1997 to February 1998, 38 intracranial aneurysms were
      embolized using GDCs. Aneurysm volume was calculated assuming that aneurysms are
      ellipsoids of the diameter in three planes. Coil volume was calculated assuming
      that detachable coils are cylinder of primary coil. Coil compaction was observed
      in aneurysms embolized at a volume embolization ratio under 21%. There was no
      coil compaction in aneurysms embolized at a volume embolization ratio of over
      21%. Measurement of the volume embolization ratio is useful to predict the coil
      compaction. Intracranial aneurysms should be embolized at a volume embolization
      ratio of 25-33%.

PMID- 20673470
TI  - Morphological Study of Carotid Artery of WHHL Rabbit after Balloon Dilatation.
AB  - SUMMARY: We performed balloon dilatation in the carotid artery of WHHL rabbits
      and examined subsequent morphological alteration over time. The balloon was
      inserted as far as the carotid bifurcation and observations were made on the
      morphological alteration after dilatation in the atherosclerotic intimal
      thickening from immediately after balloon dilatation over a period of ten months.
      Immediately after balloon dilatation, endothelial cells came of circularly and
      stretching, fragmentation off elastic fibers and coming off of smooth muscle
      cells of the media were confirmed. No change in the degree of thickening after
      dilatation was seen in the atherosclerotic intimal thickening of the carotid
      bifurcation. Three weeks later, endothelium covering except some parts, circular
      neointima and fibrosis of the media were observed; foamy cells had accumulated in
      the upper layer of the atherosclerotic intimal thickening, and that region was
      not yet covered with endothelial cells. The progress of fibrous intimal
      thickening so as to keep the lumen smooth was seen up to six months later, but
      foamy cells were not found in the neointima.

PMID- 20673471
TI  - Percutaneous Transluminal Angioplasty (PTA) with Wallstent for Internal Carotid
      Artery Stenosis. A Case Report.
AB  - SUMMARY: A 67 year-old male who had suffered from myocardial infarction, was
      admitted to our clinic to examine his internal carotid artery stenosis revealed
      by preoperative study for heart surgery. Although he had no neurological
      symptoms, the angiograms showed severe stenosis of his right internal carotid
      artery. To improve stenotic internal carotid artery, PTA was performed employing
      a selfexpanding stent. The stenotic right internal carotid artery was improved
      from 75% to 11% immediately after the stenting though restenosis mildly occurred
      up to 16% three months later. No complication occurred during this stenting
      procedure. Afterwards the patient uneventfully received coronary artery bypass
      grafting (CABG) surgery.

PMID- 20673472
TI  - Efficacy of palmaz stent deployment for subclavian artery stenosis.
AB  - SUMMARY: Percutaneous angioplasty is a useful method for improvement of posterior
      circulation of the brain in subclavian artery stenosis and occlusion. Recently,
      the Palmaz stent was introduced for peripheral vessels stenosis. We evaluated the
      efficacy and care point of Palmaz stent deployment for subclavian artery stenosis
      in seven cases (5 stenosis and 2 occlusion) with symptoms and a mean age of 65.1
      years. The stents could be deployed exactly at the stenotic region in all cases.
      The pressure gradient disappeared in all cases, and the clots were fixed between
      vessel wall and stent. Antegrade circulation and significant clinical symptoms
      improvement were obtained in all cases. In angioplasty of subclavian artery
      stenosis, as compared with balloon angioplasty alone, Palmaz stent is a very
      useful device with fewer complications including distal thrombosis of the
      vertebrobasilar circulation.

PMID- 20673473
TI  - The "over the core wire" technique for detachable coil retrieval.
AB  - SUMMARY: We report four cases of malpositioned detachable coil retrieval. In all
      cases, the malpositioned coils were retrieved without additional neurological
      deficits. The stretched core wire was grasped with a fixed-loop snare (Gooseneck
      microsnare), and the detachable coil was retrieved using an over the core wire
      technique with a hydrophilic microcatheter.

PMID- 20673474
TI  - Application of three dimensional angiography for diagnosis of patients and
      intravascular surgery. Part 1.
AB  - SUMMARY: We examined newly developed three-dimensional angiography to understand
      the anatomy for surgery and for intravascular surgery in order to decide when
      treatment should be stopped. The subjects were 23 patients chosen randomly
      (angiography, 22). The diagnoses in these patients included aneurysm (5),
      arteriovenous malformation (6), meningioma, glioma, vascular tumours of the brain
      and the neck (5), and vascular diseases (6) including carotid artery stenosis,
      Moya-Moya disease, middle cerebral artery occlusion, and megadolico-ectasia (6).
      The new technique was used for intravascular surgery in six cases, which allowed
      the neck of the aneurysm and the bifurcation to be revealed. This method is
      useful for determining whether another coil should be inserted. In patients with
      basilar top aneurysm using this technique during coil embolization the intra
      aneurysmal blood flow disappeared because complete embolization was performed.
      This technique was more useful during coil embolization, especially to decide the
      timing of withdrawal in intravascular surgery compared with conventional DSA.

PMID- 20673475
TI  - Vertebral arteriovenous fistula treated by embolization technique. Report of
      three cases.
AB  - SUMMARY: Three patients with vertebral arteriovenous fistulae are described.
      Transarterial embolization by microcoils and balloons was used in each case and
      the fistula was completely occluded in one case immediately after embolization.
      Another two cases with partial obliteration of the fistula were followed and
      showed complete occlusion of the fistula after a one year follow-up. After
      embolization of the fistula, each patient improved in clinical signs and symptoms
      and showed no complications. Transarterial embolization for vertebral
      arteriovenous fistula is a safe and effective treatment.

PMID- 20673476
TI  - Spinal Dural AVF Two Cases with MRI Follow-up.
AB  - SUMMARY: Spinal dural arteriovenous fistula (d-AVF) is one of the arteriovenous
      malformations that are treatable by surgery or embolization. We present two cases
      treated by embolization and stress the necessity of early diagnosis and
      treatment, and the usefulness of T2WI on MRI for follow-up after embolization.
      One was a 51-year-old man who presented with gait disturbance and sphincter
      dysfunction. MRI revealed diffuse swelling on T1WI, and intramedullary high
      signal intensity on T2WI. A spinal d-AVF was found through tiny
      radicullomeningeal arteries via the right Th12 intercostal artery that drained
      into engorged retromedullary veins. The spinal d-AVF was embolized with 50% NBCA.
      Six months after the embolization, he was able to go back to his job, T2WI showed
      disappearance of the high signal intensity, which was confirmed at angiography
      one year after the embolization. The other case was a 62-year-old man who
      presented with sensory disturbance and gait disturbance. MRI showed the same
      findings, without the flow voids on them in case 1. The high signal area in the
      central spinal cord was thought to be syringomyelia, in which a syrinx
      subarachnoid shunt was tried in vain. On the surface of the spinal cord,
      abnormally engorged and tortuous vessels were found. The syrinx was not
      confirmed. An angiogram showed a spinal d-AVF fed by the radicullomeningeal
      artery through a common trunk of the Th11/12 intercostal arteries with drainage
      into the retromedullary vein. The spinal d-AVF was embolized. Six months after
      the embolization, T2WI showed a decrease of high intensity areas. Early diagnosis
      and treatment are important for the prognosis of spinal d-AVF. T2WI may be the
      best way to check for recurrence.

PMID- 20673477
TI  - Embolization Method for Cavernous Sinus Fistula within the Cavernous Sinus.
AB  - SUMMARY: The complications of dural and direct cavernous sinus fistula (CCF)
      arise mainly from the specific venous route. However, embolization at an
      inappropriate site within the cavernous sinus (CS) is also a major factor.
      Therefore, we first diagrammed the surrounding structures of the CS to elucidate
      the specificity of the venous routes. Next, we divided the inside structure of
      the CS into four compartments, to examine orifices at which part we can start
      embolization with the least danger of causing complications when we have to
      embolize them within the CS. We obtained findings which will be useful to prevent
      complications such as subarachnoid haemorrhage, glaucoma, central retinal vein
      thrombosis and marked neurological impairment.

PMID- 20673478
TI  - A case of sigmoid sinus dural arteriovenous fistula after treated cavernous dural
      arteriovenous fistula.
AB  - SUMMARY: Transvenous embolization has been recommended recently as the primary
      treatment for symptomatic cavernous dural arteriovenous fistula (dural AVF). We
      present a case of sigmoid sinus dural AVF which developed after transvenous
      embolization of cavernous dural AVF. A 43-year-old man was admitted to our
      hospital because of left conjunctivill chemosis, exophthalmus and abducens nerve
      palsy. Cerebral angiograms showed left cavernous dural AVF fed by the bilateral
      internal and external carqtid arteries and draining into the enlarged left
      superior ophthalmic vein. Transfemoral approach in the cqvernous sinus via
      inferior petrosal sinus (IPS) was difficult because of the occlusive change of
      IPS. Then, direct canulation of the left superior ophthalmic vein and transvenous
      embolization using interlocking detachable coils (IDC) were performed. Dural AVF
      and clinical symptoms were disappeard rapidly after embolization. Six months
      later, follow-up cerebral angiograms showed development of a dural AVF in the
      left sigmoid sinus. The pathogenesis of dural AVF remains unclear. We suggest
      that injury to the sinus wall during endovascular procedures may have provoked
      the development of dural AVF in our case. Clinical and angiographical follow-up
      are important.

PMID- 20673479
TI  - [BMP7 signaling via BMPR1A, BMPR1B inhibits the proliferation of lung large
      carcinoma NCI-H460 cell].
AB  - BACKGROUND AND OBJECTIVE: It has been demonstrated that bone morphogenetic
      protein 7 (BMP7) may both inhibit and enhance cell proliferation of many kinds of
      cancers, but the impact of BMP7 on lung cancer cells and the exact mechanisms are
      not clear. The aim of this study is to investigate the effect of BMP7 on
      proliferation of lung carcinoma cells and explore the roles of different types of
      I receptors in BMP7 signal transmission by blocking endogenous BMPRIs. METHODS:
      The levels of expression of BMPIRs (BMP7 type I receptors) mRNA in four different
      NSCLC (human non-small cell lung tumor) cell lines and HBE (normal human
      bronchial epithelial) cell were detected by RT-PCR. The responsiveness of
      pulmonary large carcinoma NCI-H460 cell to BMP7 treatment as well as to a
      combination of BMP7 and anti-BMPIRs treatment in proliferation were detected by
      MTT. RESULTS: RT-PCR showed that NCI-H460 cells expressed all three types of
      BMPIRs; MTT showed that BMP7 inhibit the proliferation of NCI-H460 cell line.
      Blocking endogenous BMPR1A, BMPR1B obviously reversed the inhibition of BMP7 on
      the proliferation of NCI-H460 cell respectively (P = 0.003, P = 0.014). Moreover,
      blocking both endogenous BMPR1A and BMPR1B almost offset the effect of BMP7 on
      the proliferation of NCI-H460 cell completely (P < 0.001). But ACVR1A blocking
      did not affect the proliferation of NCI-H460 cell et al (P = 0.074). CONCLUSIONS:
      BMP7 signaling via BMPR1A and BMPR1B inhibits the proliferation of pulmonary
      large carcinoma cell NCI-H460.

PMID- 20673480
TI  - [microRNA expression profiling of side population cells in human lung cancer and
      preliminary analysis].
AB  - BACKGROUND AND OBJECTIVE: Recent studies indicate that the side population (SP)
      which is an enriched source of cancer stem cells (CSCs) is the root cause of
      tumor growth and development. SP appears to be highly resistant to chemo- and
      radio-therapy which becomes an important factor in tumor recurrence and
      metastasis. The aim of this study is to determine the difference of microRNA
      expression profiles between SP cells and non-SP cells so as to lay necessary
      basis for research on the function of miRNA in lung cancer stem cells. METHODS:
      SP and non-SP cells were isolated using flow cytometry and Hoechst 33342 dye
      efflux assay from human lung adenocarcinoma A549 cell. The total RNA was
      extracted. The microarray detection system was employed to analyze whether there
      was difference in miRNA expression profile between SP and non-SP cells. RESULTS:
      A total of 85 differentially expressed miRNA were found, including 32 over
      expression and 53 low-expression miRNA in SP. CONCLUSIONS: miRNA may play
      important roles in tumorigenesis of lung cancer stem cell. The study of miRNA
      contributes to elucidate the molecular mechanism of lung cancer stem cell.

PMID- 20673481
TI  - [Establishment of orthotopic lung cancer model expressing enhanced green
      fluorescent protein].
AB  - BACKGROUND AND OBJECTIVE: In vivo molecular imaging with mouse model could
      continuously and in real-time monitor the changes of the tumor. The aim of this
      study is to establish stable enhanced green fluorescent protein (EGFP) expressing
      NCI-H460 cell lines and relevant mouse model via orthotopic transplantation, and
      to study the characteristic of this model and the quantitative detection method
      of the primary tumor and metastatic lesions. METHODS: Human lung cancer NCI-H460
      cells were transfected with retroviral vector containing the EGFP. Stable high
      level expression of EGFP was maintained in the subcutaneously-growing tumors.
      Fragments of the subcutaneously growing tumor, which were comprised of EGFP
      expressing cells, were implanted by surgical orthotopic implantation (SOI) in the
      lung of nude mice. The dynamic growth of orthotopic tumor was observed using in
      vivo fluorescence imaging. The correlation of fluorescence area and tumor volume
      was tested. RESULTS: After the model established, green fluorescent can be
      observed through the flap in day 7. Tumor formation rate was 100%. Mean survival
      time of tumor-bearing nude mice was 34.2 days. The metastasis sites were the
      contralateral lung, mediastinal and hilar lymph nodes, pleura and diaphragm;
      metastasis rates were 87.5%, 75%, 25% and 12.5%, respectively. Tumor volume and
      fluorescence area was correlated (r = 0.873, P = 0.001). CONCLUSIONS: The nude
      mouse model bearing orthotopic human lung cancer expressing EGFP has been
      successfully established. The model might be used for further molecular studies
      on tumor metastasis, angiogenesis and also be applied to anti-tumor drug
      screening in preclinical stage.

PMID- 20673482
TI  - [Imaging and pathological features of percutaneous cryosurgery on normal lung
      evaluated in a porcine mode].
AB  - BACKGROUND AND OBJECTIVE: Lung cancer is one of the most commonly occurring
      malignancies and frequent causes of death in the world. Cryoablation is a safe
      and alternative treatment for unresectable lung cancer. Due to the lung being gas
      containing organ and different from solid organs such as liver and pancreas, it
      is difficult to achieve the freezing range of beyond the tumor edge 1 cm safety
      border. The aim of this study is to examine the effect of different numbers of
      freeze cycles on the effectiveness of cryoablation on normal lung tissue and to
      create an operation guideline that gives the best effect. METHODS: Six healthy
      Tibetan miniature pigs were given a CT scan and histological investigation after
      percutaneous cryosurgery. Cryoablation was performed as 2 cycles of 10 min of
      active freezing in the left lung; each freeze followed by a 5 min thaw. In the
      right lung, we performed the same 2 cycles of 5 min of freezing followed by 5 min
      of thawing. However, for the right lung, we included a third cycle of consisting
      of 10 min of freezing followed by 5 min of thawing. Three cryoprobes were
      inserted into the left lung and three cryoprobes in the right lung per animal,
      one in the upper and two in the lower lobe, so as to be well away from each
      other. Comparison under the same experimental condition was necessary. During the
      experiment, observations were made regarding the imaging change of ice-ball. The
      lungs were removed postoperatively at 3 intervals: 4 h, 3 d of postoperation and
      7 d of postoperation, respectively, to view microscopic and pathological change.
      RESULTS: The ice-ball grew gradually in relation to the increase in time, and the
      increase in number of cycles. The size of the cryolesion (hypothesis necrotic
      area) in specimens, over time, became larger in size than the size of the ice
      ball during operation, regardless of whether 2 or 3 freeze-thaw cycles were
      performed. The area of necrosis was gradually increased over the course of time.
      The hypothesis necrotic area was equal to necrosis area 3 d after cryosurgery.
      CONCLUSIONS: Percutaneous cryoablation of the lung can achieve complete ablation
      of target tissue. The freezing technique may be different depending on the
      individual circumstances of each tumor. In technology, 3 freeze-thaw cycles are
      recommended, and the range of cryoablation's effective diameter may be not
      necessarily beyond the tumor edge at least 1 cm safe border during cryosurgery.

PMID- 20673483
TI  - [Immune evasion of human lung carcinoma cell A549 suppressed by human lymphoma
      cell Jurkat via Fas/FasL pathway].
AB  - BACKGROUND AND OBJECTIVE: Tumor escape from the host immune system has been a
      major problem in immunotherapy of human malignancies. FasL/Fas-induced apoptosis
      plays an important role in various immunological processes. The aim of this study
      is to investigate the immune evasion in human lung carcinoma cell A549 induced by
      human lymphoma cell Jurkat via Fas/FasL pathway. METHODS: Jurkat cells and A549
      cells were co-cultured at different proportions. The apoptotic rates of A549
      cells were determined by flow cytometry (FCM). Protein levels of Fas, FasL and
      Caspase-8 in A549 cells were detected by Western blot. RESULTS: Survival rates of
      A549 cells gradually decreased and apoptotic rates of A549 cells were
      significantly enhanced along with ratio increasing between Jurkat and A549.
      Meanwhile, the protein levels of Fas and Caspase-8 gradually increased in A549
      cells, and the protein levels of FasL had no significant difference in all
      groups. CONCLUSIONS: The Jurkat cells might decrease the survival rates of A549
      cells and enhanced its apoptosis and immune evasion partly via Fas/FasL pathway.

PMID- 20673484
TI  - [Effect of sCD40L combined with vinorelbine on lung adenocarcinoma cell A549].
AB  - BACKGROUND AND OBJECTIVE: The results of published data on the effect of CD40
      signal related to cancer cell sensitivity to chemotherapy are inconclusive. The
      aim of this study is to investigate the effect of soluble CD40 ligand (sCD40L)
      combined with vinorelbine on lung adenocarcinoma cell line A549. METHODS: Lung
      adenocarcinoma A549 cells were chosen as target cells and CD40 signal was
      stimulated by sCD40L. MTT assay and flow cytometry were used to determine the
      changes of cell proliferation, cell cycle and apoptosis of A549 cells treated by
      vinorelbine after CD40 was stimulated. The activity of Caspase-3 was measured
      using Caspase-3 cellular activity assay kit plus. RESULTS: After CD40
      stimulation, an increase of inhibition on CD40 positive cell line A549
      proliferation was confirmed when vinorelbine was added (P < 0.05). However, no
      significant changes were shown in apoptosis and cell cycle (P > 0.05). On the
      other hand, the activity of Caspase-3 was substantially decreased (P < 0.05).
      CONCLUSIONS: Stimulation of CD40 can increase lung adenocarcinoma cell line A549
      sensitivity to vinorelbine, which may be through a non-apoptosis, Caspase
      independent mechanism, and not associated with the inhibition of cell cycle.

PMID- 20673486
TI  - [A study on the application of 18F-FDG-PET-CT for the radiotherapy of patients
      with stage III non-small cell lung cancer].
AB  - BACKGROUND AND OBJECTIVE: PET-CT have emerged as powerful imaging tools in
      radiotherapy to add information that might lead to a change in GTV definition in
      patients with non-small cell lung cancer (NSCLC). The aim of this study was to
      investigate the impact of co-registering 18F-FDG-PET-CT images on the gross tumor
      volume (GTV), the planning target volume (PTV), and critical organ dose in
      radiation therapy planning of NSCLC. METHODS: Thirty patients with stage III
      NSCLC, referred for radical radiation therapy, underwent PET-CT scanning. GTV was
      delineated on the CT imaging and PET-CT fused imaging respectively. The two
      images were used to develop the radiotherapy planning at the GE Advantage Sim 6.0
      workstation. Dose-volume histograms (DVH) parameters were selected to be
      paralleled to compare the quality of the two plans and the impact of PET-CT on
      radiation plan (RP) was further analyzed. RESULTS: (1) PET-CT image changed the
      clinical stage: 3 patients (10%) upstaged and 3 patients (10%) downstaged. (2)
      PET-CT image altered GTV and PTV: GTV and PTV was decreased by PET-CT image
      fusion in 18 patients (60%) and was increased in 12 patients (40%). A significant
      (> 25%) treatment volume modification was observed in 17 patients (56.67%). (3)
      PET-CT image changed the parameters of DVH: to deliver the same target dose of 60
      Gy in 30 fractions, all dose-volume characteristics decreased in treatment
      planning for the 18 patients with decreased PTV based on PET-CT; the issue was
      the contrary for the 12 patients who had enlarged PTV based on PET-CT.
      CONCLUSIONS: The use of the co-registration of PET-CT significantly reduced
      inaccurate outlining of the GTV and/or to geographic misses.

PMID- 20673485
TI  - [A prospective randomized study of the radiotherapy volume for limited-stage
      small cell lung cancer: a preliminary report].
AB  - BACKGROUND AND OBJECTIVE: Controversies exists with regard to target volumes as
      far as thoracic radiotherapy (TRT) is concerned in the multimodality treatment
      for limited-stage small cell lung cancer (LSCLC). The aim of this study is to
      prospectively compare the local control rate, toxicity profiles, and overall
      survival (OS) between patients received different target volumes irradiation
      after induction chemotherapy. METHODS: LSCLC patients received 2 cycles of
      etoposide and cisplatin (EP) induction chemotherapy and were randomly assigned to
      receive TRT to either the post- or pre-chemotherapy tumor extent (GTV-T) as study
      arm and control arm, CTV-N included the positive nodal drainage area for both
      arms. One to 2 weeks after induction chemotherapy, 45 Gy/30 Fx/19 d TRT was
      administered concurrently with the third cycle of EP regimen. After that,
      additional 3 cycles of EP consolidation were administered. Prophylactic cranial
      irradiation (PCI) was administered to patients with a complete response. RESULTS:
      Thirty-seven and 40 patients were randomly assigned to study arm and control arm.
      The local recurrence rates were 32.4% and 28.2% respectively (P = 0.80); the
      isolated nodal failure (INF) rates were 3.0% and 2.6% respectively (P = 0.91);
      all INF sites were in the ipsilateral supraclavicular fossa. Medastinal N3
      disease was the risk factor for INF (P = 0.02, OR = 14.13, 95% CI: 1.47-136.13).
      During radiotherapy, grade I, II weight loss was observed in 29.4%, 5.9% and
      56.4%, 7.7% patients respectively (P = 0.04). Grade 0-I and II-III late pulmonary
      injury was developed in 97.1%, 2.9% and 86.4%, 15.4% patients respectively (P =
      0.07). Median survival time was 22.1 months and 26.9 months respectively. The 1
      to 3-year OS were 77.9%, 44.4%, 37.3% and 75.8%, 56.3%, 41.7% respectively (P =
      0.79). CONCLUSIONS: The preliminary results of this study indicate that irradiant
      the post-chemotherapy tumor extent (GTV-T) and positive nodal drainage area did
      not decrease local control and overall survival while radiation toxicity was
      reduced. But the current sample size has not met designed requirements, and
      further investigation is warranted before final conclusions could be drawn.

PMID- 20673487
TI  - [Clinical significance and diagnostic value of Survivin autoantibody in non-small
      cell lung cancer patients].
AB  - BACKGROUND AND OBJECTIVE: Lung cancer is one of the most common cancers worldwide
      and causes more deaths per year than other cancers. Autoantibody was one hotspot
      in tumor marker research. But the clinical value of Survivin autoantibody is not
      clear in lung cancer patients at present. The aim of this study is to determine
      whether Survivin autoantibody could be used as a diagnostic factor of lung cancer
      and what the clinical value of Survivin autoantibody was in nonsmall cell lung
      cancer (NSCLC). METHODS: Survivin cDNA sequence was obtained by RT-PCR and
      inserted into prokaryotic expression vector pET30a(+). Fusion protein of Survivin
      was expressed in E. coil BL21(DE3). SDS-PAGE and Western blot were used to
      confirm the fusion protein. The Survivin protein was purified by Ni-NTA agarose
      affinity chromatography. At last, indirect ELISA was used to detect Survivin
      autoantibody level in the serums of 215 samples from NSCLC patients and serums
      from 20 samples of nonmalignant lung disease patients as well as 89 samples of
      healthy persons were also detected as control. RESULTS: The recombinant vector
      pET30a(+)/Survivin was contructed and the Survivin protein is successfully
      expressed in E.coil BL21(DE3) as inclusion body. Indirect ELISA was done to
      detect Survivin autoantibody in these serums using purified Survivin protein. It
      was shown that the positive rate of Survivin autoantibody was 19.5%, with a
      specificity of 88.9% in NSCLC patients. The expression of Survivin autoantibody
      has correlation with the volume of tumor and the metastasis of tumor in NSCLC
      patients (P < 0.05). In our research, positive detection rate of NSCLC was much
      improved by detecting Survivin autoantibody combined with CEA compared to other
      tumor markers combined with CEA. CONCLUSIONS: In this study, purified fusion
      protein of Survivin was successfully obtained. Indirect ELISA for detecting
      Survivin autoantibody in serum of NSCLC patients using purified Survivin protein
      was established. Our results indicated that Survivin autoantibody as a latent
      value of tumor marker could be used for clinical diagnosis in NSCLC patients.

PMID- 20673488
TI  - [Safety analysis of ambulatory chemotherapy in lung cancer].
AB  - BACKGROUND AND OBJECTIVE: Ambulatory chemotherapy has now been a popular way of
      treatment in developed countries, for its less medical costs and incidence of
      adverse events. The aim of this study is to estimate the feasibility and safety
      of ambulatory chemotherapy in lung cancer in Shanghai chest hospital. METHODS:
      Medical data including performance status, cycles of chemotherapy, pathologic
      type, adverse events in hospital and adverse events after discharge from
      hospital. RESULTS: We estimated a total of 1 573 lung cancer patients admitted in
      Shanghai chest hospital, during October 2008 to April 2009, including 416
      patients treated in the way of ambulatory chemotherapy, 1 157 patients treated in
      the routine way. Rate of grade III/IV gastrointestinal toxicity was fewer in the
      ambulatory chemotherapy group (21.88%) than routine chemotherapy group (P <
      0.01); meanwhile, rate of leukopenia was higher in the ambulatory chemotherapy
      group (49.28%) than routine chemotherapy group (35.0%)(P < 0.01). Days of
      hospitalization and medical costs were less in the ambulatory chemotherapy group
      (4.48 d vs 14.04 d, 6 911.32 vs 14 623.59, all P < 0.01). CONCLUSIONS: Ambulatory
      chemotherapy is a favorable way to promote.

PMID- 20673489
TI  - [Expression and clinical significance of mTOR and PTEN in non-small cell lung
      cancer].
AB  - BACKGROUND AND OBJECTIVE: It has been proved that mTOR was an important signal
      transduction molecular and protein kinase regulating cell growth and
      proliferation, and mTOR could activate the downstream protein effector. PTEN
      could negatively regulate mTOR signal pathway and inhibit its activity. The aim
      of this study is to detect the mRNA expression levels of mTOR and PTEN gene,
      which are the key genes of mTOR signaling pathway in human non-small cell lung
      cancer (NSCLC) tissue. The relationship between mTOR signaling pathway and NSCLC
      is also explored. METHODS: Lung cancer tissue specimens were obtained from 65
      patients. Adjacent-tumor non-small cell lung cancer tissues from the 30 patients
      were served as control. The RT-PCR technique was used to detect the mTOR and PTEN
      gene expression levels. RESULTS: The average mRNA expression levels of mTOR gene
      were significantly higher (0.23 +/- 0.16) in lung cancer than in adjacent-tumor
      tissue (0.12 +/- 0.09)(P < 0.01). The average mRNA expression levels of PTEN gene
      were (0.19 +/- 0.28) in lung cancer, while the mRNA expression levels of PTEN
      gene were (0.53 +/- 0.28) in adjacent-tumor tissue (P < 0.01). The levels of PTEN
      gene expression in non-small cell lung cancer were significantly lower than that
      in adjacent-tumor lung tissue. There are not significant relationship between
      mTOR and PTEN gene expression levels and patients' age, gender, pathological
      type, differentiation, lymph node metastasis, except tumor size. CONCLUSIONS: The
      expression of mTOR is activated in NSCLC. The expression of PTEN is absent or
      decreased. The mTOR activated in NSCLC may be correlate with the absent or
      decreased of PTEN. The absent or decreased expression of PTEN and the actived
      mTOR may play important roles in carcinogenesis and metastasis of NSCLC.

PMID- 20673490
TI  - [Correlation between pre-treatment anemia and prognosis in non-small cell lung
      cancer patients].
AB  - BACKGROUND AND OBJECTIVE: The patients with non-small cell lung cancer (NSCLC)
      might contract anemia, however, whether anemia is one of the independent
      prognostic factors to the patients with NSCLC is still controversial. So the aim
      of this study is to investigate the correlation between anemia and overall
      survival (OS) in patients with NSCLC. METHODS: 1 018 patients with operable NSCLC
      were retrospectively analyzed in our hospital from January 2000 to December 2008.
      RESULTS: The occurrence of anemia before operation was 252/1 018 (24.1%). The OS
      in NSCLC patients without anemia was (2 425.98 +/- 50.03) days, and the OS in
      patients with anemia was (2 107.15 +/-93.86) days. There was significant
      difference in the OS between them (P = 0.001). The patients with anemia in stage
      I had shorter survival time than those without anemia (P < 0.001). But there was
      no difference in other stage patients. TNM stage, gender, tumor size and lymph
      nodes metastasis were correlated with OS using Cox regression analysis.
      CONCLUSIONS: Anemia is correlated with survival in operable NSCLC patients.
      Moreover, it is an independent prognostic factor in NSCLC patients with stage I.

PMID- 20673491
TI  - [Detecting EGFR autoantibodies in serums of NSCLC patients with peptide array].
AB  - BACKGROUND AND OBJECTIVE: Autoantibodies as new tumor markers may play an
      important role in the early diagnosis and evaluating the prognosis of lung
      cancer. In this study, we detect epidermal growth factor receptor (EGFR)
      autoantibodies using peptide array and screen the epitopes which are recognized
      by EGFR autoantibodies. METHODS: Peptide array covering the extracellular domain
      of EGFR protein was synthesized by a synthesizer (ASPSL) made by Intavis company.
      EGFR autoantibodies in the serums of non-small cell lung cancer patients was
      detected using peptide array. RESULTS: Six of 20 patients were found to have EGFR
      autoantibodies. The positive rate is 30%. Nine high frequency spots were found in
      the 6 positive patients and 8 high frequency spots clustered in the III and IV
      domains. CONCLUSIONS: These findings will offer new clues for the further studies
      of EGFR and EGFR autoantibodies.

PMID- 20673492
TI  - [Progress of lymphadenectomy on lung cancer surgery].
AB  - Lymphatic metastasis is the main metastatic route for lung cancer, and is also
      one of the most important prognostic factors. Therefore, lymph node dissection
      has been an important procedure in standard lung cancer surgery. But so far, the
      mode and the extent of lymph node dissection during surgery are controversial for
      lung cancer in different pathological types, stages, or in different lobes. In
      this review, we summarize advances on the clinical significance, modes and
      extents of lymph node dissection during lung cancer surgery.

PMID- 20673493
TI  - [Research progresses of albumin-bound paclitaxel in the treatment of non-small
      cell lung cancer].

PMID- 20673494
TI  - [Meeting reports for the launch of Chinese Association on Tobacco Control Smoking
      and Disease Control Committee and the proposal].

PMID- 20673497
TI  - [Effects of vitamin C on A549 cell proliferation, apoptosis and expressions of
      Caspase, Survivin].
AB  - BACKGROUND AND OBJECTIVE: It was proven that Vitamin C could inhibit the growth
      of many types of tumors as an antioxidant. The aim of this study is to explore
      role of Vitamin C in proliferation and apoptosis of lung carcinoma cell line A549
      and the underlying mechanism. METHODS: A549 cells were cultured in vitro and
      incubated with Vitamin C. The cell viability was measured by growth curve and
      clonogentic assay. Flow cytometry was used to analyze cell cycle and detect
      apoptosis. The levels of expression of Caspase-3 mRNA and Survivin mRNA were
      detected by RT-PCR. RESULTS: Vitamin C of 400 microg/mL, 4 mg/mL significantly
      inhibited the growth of A549 cell lines (P = 0.024, P = 0.015, respectively).
      Flow cytometry showed that the cells major stagnation stayed in the G0/G1 and S
      phase and the apoptotic rate increased with time prolonged. Vitamin C
      signifiantly up-regulated the expression of Caspase-3 mRNA, but had no effect on
      Survivin mRNA. CONCLUSION: Vitamin C can inhibit the proliferation of A549, block
      A549 cells in G0/G1 and S phase, and induce apoptosis of A549 cells. Apotosis
      occurred by up-regulated the expression of Caspase-3.

PMID- 20673495
TI  - [Pemetrexed combined DDP in the treatment of advanced non-small cell lung cancer:
      a case report and literature review].
AB  - BACKGROUND AND OBJECTIVE: The aim of this study is to integrate with literature
      review, and explore the value of treatment of advanced non-small cell lung cancer
      with second line. METHODS: For the metastatic progressive non-small cell lung
      adenocarcinoma patient, the evaluation of efficacy for complete response (CR)
      with endostar combined GC, the sequential treatment with gefitinib, used
      pemetrexed combined DDP as the second line treatment, followed up and observed
      with the progression free survival (PFS) and survival time of patient. RESULTS:
      Pemetrexed combined DDP in the treatment of 5 cycles, the evaluation of lung
      cancer efficacy for CR, bone metastasis was steady, PFS was 6.6 months, survival
      time is 22 months now, improved the quality of living life. CONCLUSIONS: For
      advanced non-small cell lung adenocarcinoma recurrence and metastasis, after the
      treatment of first line and maintenance therapy, selecting adequately pemetrexed
      combined DDP, as the second line treatment, can prolong the lifetime and improve
      the quality of life.

PMID- 20673498
TI  - [Interference of homologous sequences on the SNP study of CYP2A13 gene].
AB  - BACKGROUND AND OBJECTIVE: It has been proven that cytochrome P450 enzyme 2A13
      (CYP2A13) played an important role in the association between single nucleotide
      polymorphisms (SNP) and human diseases. Cytochrome P450 enzymes are a group of
      isoenzymes, whose sequence homology may interfere with the study for SNP. The aim
      of this study is to explore the interference on the SNP study of CYP2A13 caused
      by homologous sequences. METHODS: Taqman probe was applied to detect distribution
      of rs8192789 sites in 573 subjects, and BLAST method was used to analyze the
      amplified sequences. Partial sequences of CYP2A13 were emplified by PCR from 60
      cases. The emplified sequences were TA cloned and sequenced. RESULTS: For
      rs8192789 loci in 573 cases, only 3 cases were TT, while the rest were CT
      heterozygotes, which was caused by homologous sequences. There are a large number
      of overlapping peaks in identical sequences of 60 cases, and the SNP of 101 amino
      acid site reported in the SNP database is not found. The cloned sequences are 247
      bp, 235 bp fragments. CONCLUSION: The homologous sequences may interfere the
      study for SNP of CYP2A13, and some SNP may not exist.

PMID- 20673499
TI  - [Expression and its clinical significance of SHP2 in non-small cell lung cancer].
AB  - BACKGROUND AND OBJECTIVE: Precious studies proven that aberrant tyrosine
      phosphorylation has linked with cancer. The aim of this work is to study the
      expression and significance of SHP2 in non-small cell lung cancer (NSCLC) through
      tissue microarray technique and immunohistochemical method. METHODS: Eighty NSCLC
      specimens were constructed into tissue microarray and performed using
      immunohistochemistry. RESULTS: The total positive rates of SHP2 were 70.7%
      (56/80) in NSCLC, 72.5% (29/40) in squamous cell carcinoma and 75% (27/40) in
      adenocarcinoma, which was not significant difference in sex, age, the size of
      tumor, histology, clinical stages and differentiation (P > 0.05), the positive
      rates of SHP2 were significantly higher in the cases with lymphnode metastasis
      than those without (P < 0.05). CONCLUSION: The expression rate of SHP2 is high
      and closely correlated to lymphnode metastasis in NSCLC, which implies the
      occurrence and development of lung cancer maybe related to SHP2, and SHP2 maybe a
      new marker and therapeutic targets for lung cancer.

PMID- 20673500
TI  - [Research on fast track surgery application in lung cancer surgery].
AB  - BACKGROUND AND OBJECTIVE: Fast track surgery (FTS) is a systematical method to
      accelerate the recovery of surgical patients by reducing the physical and mental
      trauma stress of them. The research is to investigate the feasibility of FTS
      application in lung cancer surgery. METHODS: A total of 80 cases of lung cancer
      patients with single leaf lobotomy resection were randomized into two groups.
      While the experimental group was treated with the conception of FTS, and the
      control group was treated with the traditional methods. The incident rate of post
      operation pain degrees, telecasts, pleural effusion, the post-operation time stay
      in hospital time and the total cost during hospitalization in two groups were
      compared respectively. RESULTS: In FTS group: the VAS score of post-operation
      pain at 1 h, 6 h, 12 h, 24 h and 48 h all significantly decreased compared to the
      traditional therapy group. The incidence rate of telecast was 10.53%. The
      incidence rate of pleural effusion was 26.31%. The length of stay after operation
      was (4 +/- 1) d and the total cost was RMB 15 600 +/- 7 600. In the control
      group, the above values were 77.78%, 33.33%, 22.22%, (9 +/- 1) d, RMB 23 600 +/-
      5 400, respectively. The post operation pain (VAS method) of FTS group was
      remarkablely below the control group. There has significant difference of the
      incident rate of telecasts, stay time in hospital and the total cast in two
      groups (P < 0.05). No significant difference was observed in the incident rate
      ofpleural effusion. CONCLUSION: The new methods of FTS can apparently accelerates
      recovery after lung cancer resection, reduces complications, shorten timestay in
      hospital and cut down the total cost.

PMID- 20673501
TI  - [Detection of EGFR and COX-2 expression by immunohistochemical method on a tissue
      microarray section in lung cancer and biological significance].
AB  - BACKGROUND AND OBJECTIVE: Epidermal growth factor receptor (EGFR) and
      cyclooxygenase-2 (COX-2), which can regulate growth, invasion and metastasis of
      tumor through relevant signaling pathway, have been detected in a variety of
      solid tumors. The aim of this study is to investigate the biological significance
      of EGFR and COX-2 expression in lung cancer and the relationship between them.
      METHODS: The expression of EGFR and COX-2 was detected in 89 primary lung cancer
      tissues, 12 premalignant lesions, 12 lymph node metastases, and 10 normal lung
      tissues as the control by immunohistochemical method on a tissue microarray
      section. RESULTS: EGFR protein was detectable in 59.6%, 41.7%, and 66.7% of
      primary lung cancer tissues, premalignant lesions and lymph node metastases,
      respectively; COX-2 protein was detectable in 52.8%, 41.7%, and 66.7% of primary
      lung cancer tissues, premalignant lesions and lymph node metastases,
      respectively, which were significantly higher than those of the control (P <
      0.05). The positive ratios and the levels of the expression of EGFR and COX-2
      proteins were closely related to histological type, clinical stage and lymph node
      metastasis of lung cancer (P < 0.05), but not to histological grade, sex and age
      (P > 0.05). COX-2 expression was related to gross type (P < 0.05). A highly
      positive correlation was observed between EGFR and COX-2 expression (P < 0.01).
      CONCLUSION: Overexpression of EGFR and COX-2 may play an important role in the
      tumorgenesis, progression and malignancy of lung cancer. Detection of EGFR and
      COX-2 expression might be helpful to diagnosis and prognosis of lung cancer.

PMID- 20673502
TI  - [Vinorelbine plus oxaliplatin versus vinorelbine plus cisplatin for advanced non
      small cell lung cancer: a systematic review].
AB  - BACKGROUND AND OBJECTIVE: Cisplatin (DDP) plus vinorelbine (NVB) constitute the
      first-line regimen (NP regimen) for non-small cell lung cancer (NSCLC).
      Oxaliplatin (OXA) is another effective drug in treatment of NSCLC with mild
      toxicities to gastrointestinal tract, kidney and bone marrow. The aim of this
      study is to evaluate the efficiency and safety between NVB plus OXA (NO) regimen
      and NP regimen for advanced NSCLC. METHODS: We searched CBM CNKI, VIP, Cochrane
      Library, PubMed, EMBASE, ASCO etc. conference proceedings and internet
      information. Randomized controlled trials of NO versus NP for advanced NSCLC were
      included; we evaluated the quality of the included studies and analyzed data by
      Cochrane Collaboration's RevMan 5.0 software. RESULTS: Fourteen randomized trials
      involving 1 270 patients were included. There were no statistical differences
      between NO and NP in overall response rate, disease control rate, 1-year survival
      rate, anemia and thrombocytopenia. Gastrointestinal toxicity, leucopenia,
      alopecia and kidney toxicity were more serious in NP (P < 0.05), but neuritis was
      more serious in NO, with significant difference (P < 0.05). CONCLUSION: The
      clinical efficacy of NO and NP for advanced NSCLC was similar, but the side
      effects were different. The toxicity of NO has the tendency to be more tolerable.

PMID- 20673503
TI  - [Correlation of postoperative serum VEGF levels with platelet counts in non-small
      cell lung cancer].
AB  - BACKGROUND AND OBJECTIVE: It ha been proven that serum vascular endothelial
      growth factor (VEGF) concentration was elevated significantly after surgery in
      patients of non-small cell lung cancer (NSCLC). Platelet may be the main resource
      of serum VEGF. The aim of this study is to investigate the correlation between
      postoperative dynamic changes of serum VEGF levels and platelet counts in
      patients of NSCLC who underwent surgery. METHODS: Serum VEGF levels were
      determined in 76 patients of NSCLC who were treated with surgery by ELISA (enzyme
      linked immunosorbent assay) method before operation and on postoperative day 1,
      7. At the same day the concentrations of platelet were determined. RESULTS (1)
      Serum VEGF in patients of NSCLC on preoperative day, postoperative 1 day and 7
      day were (842.06 +/- 527.24) pg/mL, (1 119.28 +/- 609.62) pg/mL, (1 574.09 +/-
      873.38) pg/mL, respectively (P < 0.001); (2) Platelet counts in patients of NSCLC
      on preoperative day, postoperative 1 day and 7 day were (230.42 +/- 82.56 x
      10(9)/L, (196.47 +/- 81.48) x 10(9)/L, (237.90 +/- 86.94) x 10(9)/L; the value on
      postoperative 1 day was the lowest (P < 0.001); (3) On postoperative 7 day, serum
      VEGF in the group of lower than the mean and higher than the mean were
      respectively (1 398.81 +/- 734.00) pg/mL and (1 842.86 +/- 1 006.63) pg/mL (P =
      0.043). CONCLUSION: Serum VEGF in patients of NSCLC after surgery were elevated.
      In the group of higher platelet counts, serum VEGF increased more significantly.

PMID- 20673504
TI  - [A meta analysis on the relationship between myeloperoxidase G-463A genetic
      polymorphisms and lung cancer susceptibility].
AB  - BACKGROUND AND OBJECTIVE: The relationship between myeloperoxidase G-463A genetic
      polymorphisms and lung cancer susceptibility has been studied extensively.
      However, the outcomes are not consistent. The aim of this study is to evaluate
      the relationship between myeloperoxidase genetic polymorphisms and lung cancer
      susceptibility by meta analysis. METHODS: Documents published were retrieved
      through databases associated with the study. Taking into account the
      possibilities of heterogeneity of the studies, a statistical test for
      heterngeneity was performed. The odds ratio and 95% CI were used to evaluate the
      risks. The meta analysis was applied with RevMan software 4.2, and the forest
      plot and funnel plot of meta analysis were worked out. RESULTS: A total of 5 381
      cases and 5 827 controls from studies for Caucasian and a total of 1 558 cases
      and 1 755 controls from studies for East Asians were included. For Caucasian the
      pooled OR was 0.91 (95% CI: 0.81-1.02); For East Asians, the pooled OR is 0.83
      (95% CI: 0.63-1.09). Publication bias exits in the study for Caucasian, but not
      for East Asians. CONCLUSION: The results of this study indicated that the
      polymorphism of myeloperoxidase G-463A was not significantly associated with the
      lung cancer risk for Caucasian or East Asians. However, further studies for the
      East Asians is needed for the few subjects.

PMID- 20673505
TI  - [Diagnotic value of the combined determination of telomerase activity in induced
      sputum, pleural effusion and fiberobronchoscopic biopsy samples in lung cancer].
AB  - BACKGROUND AND OBJECTIVE: It has been proven that telomerase activation
      correlates with the carcinogenesis, aggressiveness and turnover of lung cancer.
      Telomerase is one of the improtant molecular biomarkers for diagnosis and
      targeting therapy in lung cancer. The aim of this study is to investigate the
      diagnostic value of the combined determination of telomerase activity in induced
      sputum, pleural effusion and fiberobronchoscopic biopsy in lung cancer patients.
      METHODS: The technique of TRAP (telomeric repeat amplification protocal)-PCR
      ELISA was employed to detect telomease levels of induced sputum, pleural effusion
      and fiberobronchoscopic biopsy in 80 lung cancer patients with pleural effusion
      and 50 benign pulmonary disease patients with pleural effusion. RESULTS:
      Telomemse levels of induced sputum, pleural effusion and fiberobronchoscopic
      biopsy were all significantly higher in patients with lung cancer than those with
      benign pulmonary disease (P < 0.001). There was no significant difference in the
      level of telomerase activity between different pathologic types (P > 0.05). The
      sensitivity of induced sputum, pleural effusion and fiberobronchoscopic biopsy
      were 62.5% (50/80), 46.3% (37/80) and 60.0% (48/80), respectively. The
      specificity were 72.0% (36/50), 66.0% (33/50) and 70.0% (35/50), respectively.
      The overall accuracy were 66.2% (86/130), 53.8% (70/130) and 63.8% (83/130),
      respectively. The sensitivity, specificity and overall accuracy of combined
      induced sputum, pleural effusion and fiberobronchoscopic biopsy were 85.0%
      (68/80), 78.0% (39/50) and 82.3% (107/130), respectively. The sensitivity of
      telomease level in combined detection for diagnosis of lung cancer was much
      higher than that in single sample detection (P < 0.01). CONCLUSION: The
      sensitivity of telomease activity in combined three samples was the highest. It
      can further improve the accuracy for the diagnosis of lung cancer with pleural
      effusion.

PMID- 20673506
TI  - [BSD2000 deep hyperthermia combined with chemotherapy of PT regimen in patients
      with non-small cell lung cancer].
AB  - BACKGROUND AND OBJECTIVE: The aim of this study is to determine the short-term
      efficacy, toxicity and the rate of life-quality improvement of BSD2000 deep
      hyperthermia combined with chemotherapy of PT regimen in patients with non-small
      cell lung cancer (NSCLC) by comparation with PT regimen alone. METHODS: Sixty
      patients with NSCLC were randomly divided into the treatment group and control
      group, with 30 each. The treatment group was treated with chemotherapy
      (paclitaxel: 135 mg/m2 ivdirp 3 h qd d1+cisplatin: 20 mg/m2 ivdirp qd d1-5) in
      combination with BSD2000 deep hyperthermia, and hyperthermia was positioned
      precisely and maintained for 60 min (2 times a cycle: d1, 4 after the end of
      chemotherapy within two hours). The control group was treated with chemotherapy
      alone. Treatment response in both groups were evaluated as well as side-effects
      after 3 cycles. By observing the results, comparing response rate, toxic side
      effects and quality of life improvement rate in two groups. RESULTS: The
      efficiency and the rate of life-quality improvement in the treatment group were
      63.33%, 76.67% respectively, and 36.67%, 40.00% in the control group
      respectively. There were significant differences between two groups (P < 0.05).
      The main side-effects were myelosuppression and gastrointestinal reactions, no
      significant difference between two groups (P > 0.05). CONCLUSION: BSD2000 deep
      hyperthermia combined with chemotherapy in patients with NSCLC can significantly
      increase the efficacy, response rate and quality of life improvement and without
      increasing side-effects compared to chemotherapy alone.

PMID- 20673507
TI  - [The changes of blood coagulation in surgical patients with lung cancer].
AB  - BACKGROUND AND OBJECTIVE: Patients with malignant tumor are at high risk of
      thrombophilia, which contributes to thromboembolism. Surgical treatment is one of
      the critical risk factors. In this study, changes and clinical significances of
      blood coagulation of lung cancer patients pre- and post operation were
      investigated. METHODS: A prospective, controlled study were carried out in 74
      lung disease patients, who were divided into lung cancer group and benign lung
      disease group. In each group, pre- and postoperative changes in prothrombin time
      (PT), activated partial thromboplastin time (APT), platelet count (PLT), D-dimer
      (D-D) and fibrinogen (Fib) and clinical performances were observed and compared
      in intra- and intergroups. RESULTS: The concentration of Fib both in lung cancer
      group and its subgroup (adenocarcinoma of lung) increased, preoperative
      differences between benign lung disease group and subgroup (squamous cell
      carcinoma of lung) was significant (P < 0.05). PT (postoperative 1st to 7th day)
      in lung cancer group prolonged, APTT (postoperative 3rd to 7th day) reduced, Fib
      (postoperative 3rd to 7th day) and D-D (postoperative 1st to 7th day) increased,
      PLT reduced on the 1st, 3rd day but then increased on the 5th, 7th day after
      operation, the difference between pre- and post-operation was significant (P <
      0.05). D-D and PT in lung cancer group on the 7th day was longer than in benign
      lung disease group (P < 0.05). One pulmonary thromboembolism (PTE) case in lung
      cancer group occurred, while in benign lung disease group none venous
      thromboembolism (VTE) appeared. CONCLUSION: Patients with lung cancer are in high
      hypercoagulable state, and prone to VTE. It is necessary to take some
      interventions to avoid VTE.

PMID- 20673508
TI  - [Advances of microRNAs correlated with invasion and metastasis of tumors].

PMID- 20673509
TI  - [HLA and immune of lung cancer].

PMID- 20673510
TI  - [The next generation sequencing technology and its application in cancer
      research].

PMID- 20673511
TI  - [Advances of the correlation between JAK-STAT3 signaling pathway and the
      biological behavior of non-small cell lung cancer].

PMID- 20673512
TI  - [The relationship of GLUT1 and lung cancer and its PET imaging].

PMID- 20673513
TI  - [Application of videomediastinoscopy in positive PET finding for mediastinal
      lymph node of lung cancer].
AB  - BACKGROUND AND OBJECTIVE: Positron emission tomography (PET) is used increasingly
      in staging of non-small cell lung cancer (NSCLC) as a non-invasive tool. However,
      the role of PET in mediastinal lymphatic staging of NSCLC is not clear. The aim
      of this study was to demonstrate the efficacy of mediastinoscopy in determining
      mediastinal lymphatic metastasis in cases of positive PET finding. METHODS: We
      performed PET preoperatively in 68 patients with clinically operable NSCLC
      between 2003 and 2008. Mediastinal lymphatic defined as metastasis by PET
      (SUV(max) > 2.5) was recorded. Mediastinoscopy being performed initially in all
      patients. Involvement of mediastinal lymph nodes was verified to compare the
      sensitivity and specificity of mediastinoscopy and the related PET results.
      RESULTS: From 2003 to 2008, 61 mediastinoscopy were performed. There were 38 men
      and 23 women, aged from 41 to 81 years (mean 60 years). Localization of the tumor
      was right lung in 41 patients and left lung in 20 patients. After the operation,
      45 patients were demonstrated to have N2 or N3 disease. Ten patients with N3
      mediastinal metastasis for chemotherapy, 38 patients with N2 mediastinal
      metastasis for neuadjuvant chemotherapy while lung resection and systemic
      mediastinal lymphatic dissection through thoracotomy was performed in the
      remaining 16 patients with no mediastinal metastasis. The positive prediction
      value of PET scan was 73.8% (45/61). The sensitivity, specificity, accuracy,
      positive prediction value and negative prediction value in diagnosis of
      metastasis of mediastinal lymph nodes were 93.8% (45/48), 100% (13/13), 95.1%
      (58/61), 100% (45/45), 81.3% (13/16) for mediastinoscopy, respectively.
      CONCLUSION: PET results do not provide acceptable accuracy rates. Mediastinoscopy
      still remains the gold standard for mediastinal staging of NSCLC.

PMID- 20673514
TI  - Scientific evidence on the supportive cancer care with Chinese medicine.
AB  - Complementary and alternative medicine has been increasingly utilized by cancer
      patients in developed countries. Among the various forms of complementary and
      alternative medicine, Traditional Chinese Medicine is one of the few that has a
      well constructed theoretical framework and established treatment approaches for
      diseases including cancer. Recent research has revealed growing evidence
      suggesting that Traditional Chinese Medicine is effective in the supportive care
      of cancer patients during and after major conventional cancer treatments. This
      paper succinctly summarizes some published clinical evidence and meta-analyses
      which support the usage of various Traditional Chinese Medicine treatment
      strategies including Chinese herbal medicine, acupuncture and Qigong in
      supportive cancer care.

PMID- 20673515
TI  - [The expression and prognostic significance of ERCC1 and GST-pi in lung cancer].
AB  - BACKGROUND AND OBJECTIVE: It has been known that the expression levels of ERCC1
      and GST-pi were correlated with tumorigenesis and prognosis. The aim of this
      study is to investigate the relationship between expression levels of ERCC1 and
      GST-pi, and clinicopathologic parameters and survival in patients with lung
      cancer. METHODS: The expression levels of ERCC1 and GST-pi were detected by
      immunohistochemical staining on tissue micro-array sections made of 148 cases of
      lung cancer and 7 cases of normal lung samples. The results were compared with
      relevant clinical and pathologic data. RESULTS: Positive rates of ERCC1 and GST
      pi were 36.2% and 73.6%, respectively. None of normal lung samples was positive
      staining. Positive expression of ERCC1 was significantly higher in group of non
      small cell lung cancer (NSCLC), highly differentiated and the smokers less than
      400 (P < 0.05), positive expression of GST-pi was significantly higher in group
      of non-smokers and NSCLC (P < 0.05). There were significant correlations between
      expression of ERCC1 and GST-pi (r = 0.253, P = 0.001). The 5 years survival rate
      was higher in positive expression of ERCC1. There was significant correlations
      between expression of ERCC1 and survival (P = 0.037). There was no significant
      correlations between expression of GST-pi and survival (P = 0.614). Multivariate
      analysis using Cox regression model showed that expression levels of ERCC1 and
      GST-pi were not the important independent prognostic factors for survival.
      CONCLUSION: ERCC1 and GST-pi are aberrant highly expressed in NSCLC with positive
      correlation, which indicate they might act synergistically in tumorigenesis of
      NSCLC. The positive expression of ERCC1 have better survival and may have effect
      on prognosis.

PMID- 20673516
TI  - [The sonodynamic effects of Chlorin e6 on the proliferation of human lung
      adenocarcinoma cell SPCA-1].
AB  - BACKGROUND AND OBJECTIVE: Sonodynamic therapy (SDT) is a promising new approach
      for cancer therapy. The purpose of this study is to detect the effects of SDT on
      the cell proliferation of human lung adenocarcinoma cell SPCA-1, using Chlorin e6
      as a sonosensitizing agent activated by ultrasound. METHODS: SPCA-1 and normal
      peripheral mononuclear cell (PMNC) were treated with ultrasound or Chlorin e6
      alone and combined. Cell proliferation was determined by MTT assay, and cell
      morphology was studied by inverted microscope after 6 h treated. RESULTS: 1.0 MHz
      ultrasound (1.0 W/ cm(2)-2.0 W/cm2 x 60 s) and Chlorin e6 (0.4 mg/mL-3.2 mg/mL)
      inhibited the cell proliferation of both SPCA-1 and PMNC cells in a intensity-
      and a dose-dependent manner respectively. Compared with the ultrasound (1.0 W/cm2
      x 60 s) or Chlorin e6 (0.05 mg/mL-0.2 mg/mL) alone, the inhibitory effect on the
      cell proliferation was remarkably increased by the combination of ultrasound and
      chlorin e6 in SPCA-1 cells (P < 0.05), but no same effect was observed in PMNC
      cells (P > 0.05). Compared with the ultrasound (1.0 W/cm2 x 60 s) or chlorin e6
      (0.2 mg/mL) alone, the combination treatment of ultrasound with Chlorin e6
      induced more necrotic cells in SPCA-1 cells (P < 0.05). CONCLUSION: There was a
      significant selectively inhibitory effect of sonodynamic effect with Chlorin e6
      on the SPCA-1 cell growth. Chlorin e6 may be a promising sonosensitizing agent
      for the treatment of non-small cell lung cancer.

PMID- 20673517
TI  - [Study on the prognosis of the T1a non-small cell lung cancer].
AB  - BACKGROUND AND OBJECTIVE: The new edition of the TNM staging for lung and pleural
      tumours has been finished, which put weight on the extent of primary tumor as one
      of the important prognosises. But little study has performed on the primary tumor
      extent < or = 2 cm. The aim of this study is to explore the prognosis of patients
      with tumor extent < or = 2 cm in stage I of non-small cell lung cancer, which
      helps us to choose the best treatment for these patients. METHODS: Retrospective
      study on the clinical response and survival time of whom underwent complete
      surgical resection and diagnosed as T1a of stage I NSCLC from 1998 to 2004 was
      analyzed. Data was analyzed by SPSS 17.0 software. RESULTS: Overall survival rate
      was 80.8%. By the study, age (P = 0.241), gender (P = 0.175), history of smoking
      (P = 0.845), pathologic type ( P =0.265), and systematic mediastinal
      lymphadenectomy (SML )(P = 0.918) or not, postoperative adjuvant chemotherapy or
      not ( P = 0.616) and visceral pleural invasion (P = 0.827) were not the
      prognosises of these patients. Only the tumor differentiation such as poorly
      differentiated was the important prognosis ( P = 0.01). CONCLUSION: In the tumor
      extent < or = 2 cm of stage I non-small cell lung cancer, the visceral pleural
      invasion maybe not influence the patients survival. The tumor differentiation is
      one of the important prognostic factors.

PMID- 20673518
TI  - [Immediate versus delayed topotecan after first-line therapy in small cell lung
      cancer].
AB  - BACKGROUND AND OBJECTIVE: How to prolong progression free survival (PFS) and
      overall survival (OS) of patients with small cell lung cancer (SCLC) has been one
      of the hottest issues. We retrospectively reviewed our data to compare the
      survival of immediate with delayed topotecan after first-line therapy in SCLC.
      METHODS: In our retrospective study, 53 patients with SCLC were divided into two
      groups as follow: patients receiving topotecan-containing regimen as
      maintenance/consolidation (maintenance/consolidation chemotherapy group) and
      salvage chemotherapy (salvage chemotherapy group). The Log-rank test was used to
      assess the difference in OS between two groups. Cox regression model was used for
      the multivariable analysis of independent prognostic factors. RESULTS: Twenty
      nine patients received topotecan as maintenance/consolidation treatment, whereas
      24 patients salvage chemotherapy. The response rates were 51.7% and 41.7%,
      respectively. The median survival time were 20 months and 27 months respectively
      (P = 0.89). Multivariate Cox regression analyses identified sex and stage as
      independent prognostic factors. CONCLUSION: Efficacy of first-line therapy was
      improved by topotecan maintenance/ consolidation treatment, which did not result
      in any significant survival benefits in SCLC.

PMID- 20673519
TI  - [A meta analysis of gemcitabine plus platinum chemotherapy compared with single
      agent chemotherapy in the treatment of non-small cell lung cancer].
AB  - BACKGROUND AND OBJECTIVE: Whether gemcitabine plus platinum chemotherapy is
      superior to gemcitabine or platinum single-agent chemotherapy for patients with
      non-small cell lung cancer (NSCLC) is still in dispute, and the aim of this study
      is to evaluate the efficacy and safety of gemcitabine combining platinum
      chemotherapy for patients with NSCLC. METHODS: We searched relevant randomized
      controlled trials (RCTs) from VIP, CBM, CNKI, the Cochrane library, PUBMED and
      EMBASE. We traced the related references and experts in this field and
      communicated with other authors to obtain the information that has not been
      found. We made quality assessment of qualified RCTs assessed by the exclusion and
      inclusion criteria and used RevMan 5.0 provided by the Cochrane Collaboration to
      perform meta-analysis. RESULTS: Four RCTs were eligible and included 984
      patients. Meta analysis results suggested that: compared with gecitabine single
      agent chemotherapy, the combination had a statistically significant benefit in
      increasing the response rate (OR = 3.29, 95% CI: 1.79-6.05, P = 0.000 1) and 2
      year survival rate (OR = 3.22, 95% CI: 1.45-7.12, P = 0.004) while increased the
      risk of the incidence of adverse reactions, especially the grade 3-4
      thrombocytopenia (RR = 8.16, 95% CI: 1.71-39.07, P = 0.009); compared with
      cisplatin single-agent chemotherapy, the combination had a statistically
      significant benefit in increasing the response rate (OR = 3.51, 95% CI: 2.20
      5.60, P < 0.01) and 1-year survival rate (OR = 1.67, 95% CI: 1.16-2.41, P =
      0.006) while increased the risk of the incidence of adverse reactions, especially
      the grade 3-4 thrombocytopenia (OR = 28.55, 95% CI: 14.06-57.04, P < 0.01).
      CONCLUSION: Compared with single-agent chemotherapy, the combining can
      significantly improve the efficiency and survival rate while increase the
      toxicity rare. The results still need to be proved by high quality RCTs.

PMID- 20673520
TI  - [Systematic review of the relationship between family history of lung cancer and
      lung cancer risk].
AB  - BACKGROUND AND OBJECTIVE: Fourty years ago, Tokuhata and Lilienfeld provided the
      first epidemiologic evidence of familial aggregation of lung cancer. Familial
      aggregation and increased familial risk for lung cancer have been reported in
      several studies, subsequently. But the results are not consistent with each
      other. The aim of this study is to further explore the relationship between
      family history of lung cancer and lung cancer risk. METHODS: By searching PubMed,
      CENTRAL, CBM, CNKI and VIP, we collected both domestic and overseas published
      documents before November, 2009 on family history of lung cancer and lung cancer
      risk. RevMan version 4.2 was used to perform meta-analysis on the case-control
      study results, the combined odds ratio (OR) and the 95% confidence interval (CI)
      were calculated as well. RESULTS: Twenty-eight publications were included into
      the combined analysis, which indicated that the lung cancer risk of the probands'
      first-degree relatives was 1.88 times higher than that of their controls' (P <
      0.001). In the sub-study, compared with the controls' father mother and siblings,
      the OR of the probands' father mother and siblings was 1.62 (P < 0.001), 1.96 (P
      < 0.001) and 1.92 (P < 0.001), respectively. For smoking status, lung cancer risk
      in first-degree relatives of smoking probands was 1.73 (P < 0.001) times higher
      than that of their corresponding controls'. And for non-smoking subjects the lung
      cancer risk was 1.42 (P = 0.02) times higher in proboands' first-degree
      relatives. For gender categories, lung cancer risk in first-degree relatives of
      female probands was 1.89 (P < 0.001) times higher than that of their
      corresponding controls'. And for male subjects, the lung cancer risk was 1.99 (P
      < 0.001) times higher in proboands' first-degree relatives. CONCLUSION: Lung
      cancer risk was increased in probands' first-degree relatives, and obvious
      familial aggregation of lung cancer was observed in this study.

PMID- 20673521
TI  - [Skills and the clinical application of CT guided radioactive seed 125I
      implantation in treating multiple lung metastatic masses].
AB  - BACKGROUND AND OBJECTIVE: 125I seed implantation treatment of pulmonary
      metastases, often because of complicated structure of the chest, was considered
      as restricted areas. The aim of this study is to evaluate the effectiveness of CT
      guided radioactive 125I seed implantation in treating lung metastatic tumors.
      METHODS: Totally 115 metastatic masses were found in 30 patients with CT guiding.
      125I seeds were implanted into lung metastatic masses. The approach of
      implantation was determined according to the location of the lesions (hilar
      masses, peripheral masses and masses covered by skeletal thorax). The therapeutic
      effects were evaluated by CT. RESULTS: Uniform distribution were achieved by
      single puncture in 84.3% of patients. The rest patients (15.7%) were received
      replanting. The follow-up period was 6-24 months (mean 14.6). Among 115 lesions
      in 30 cases, complete response (CR) was achieved in 80 nodes, partial response
      (PR) in 20 nodes, No change (NC) in 8 nodes and progressive disease (PD) in 7
      nodes. The total response rate was 86.9%. The one-year local control rate were
      93.9% (108/115). No severe perioperative complications occurred. CONCLUSION: CT
      guided radioactive seed 125I implantation is a safe and effective procedure in
      treating multiple lung metastatic tumor with minimal invasion.

PMID- 20673522
TI  - [Prevention and treatment of atelectasis after thoracotomy for lung cancer].
AB  - BACKGROUND AND OBJECTIVE: Atelectasis is a common complication after thoracotomy,
      and it may threaten patients' life if it was not treated correctly and properly.
      The aim of this article is to explore and discuss the prevention and treatment
      for atelectasis during the perioperative period, and also to explore new methods
      for reducing the perioperative mortality due to atelectasis after thoracotomy.
      METHODS: We retrospectively reviewed the medical records of 374 lung cancer
      patients who underwent thoracotomy in our department between Jan 2007 and Nov
      2009. RESULTS: Atelectasis occurred in 14 patients among all the 374 lung cancer
      patients who underwent thoracotomy. All the atelectasis returned to reexpansion
      after treatment. CONCLUSION: The incidence of atelectasis in these series is
      relatively low compared with the reports in literatures. Good perioperative
      preparation and perioperative treatment can remarkably decrease the incidence and
      mortality of atelectasis after thoracotomy in the treatment of lung cancer.

PMID- 20673523
TI  - [Molecular factors related to gefitinib efficacy in advanced non-small cell lung
      cancer].

PMID- 20673524
TI  - [E-cadherin/beta-catenin and the invasion and metastasis of lung cancer].

PMID- 20673525
TI  - [Reasearch advances on lung cancer stem cell].

PMID- 20673526
TI  - [Advances of microRNAs correlated with invasion and metastasis of lung cancer].

PMID- 20673527
TI  - [The clinical signifcance of expression of ERCC1 and PkCalpha in non-small cell
      lung cancer].
AB  - BACKGROUND AND OBJECTIVE: Excision repair cross-complementing 1 (Excision-Repair
      Cross-Complementing 1, ERCC1), an important member of the DNA repair gene family,
      plays a key role in nucleotide excision repair and apoptosis of tumor cells.
      Protein kinase C-alpha (Protein kinase C, PKCalpha), an isozyme in protein kinase
      C family, is an important signaling molecule in signal transduction pathways of
      tumors, which has been implicated in malignant transformation and proliferation.
      The aim of this study was to explore the clinical significance of ERCC1 and
      PKCalpha in non-small cell lung cancer (NSCLC). METHODS: The expression of ERCC1
      and PKCalpha were examined by immunohistochemistry (IHC) in the specimens of 51
      cases of NSCLC patients tissue and 21 cases of paracancerous tissue. The
      relationship between detected data and patients' clinical parameters was analyzed
      by SPSS 13.0 software. RESULTS: The positive expression rate of ERCC1 and
      PKCalpha in NSCLC tissues was significantly higher than paracancerous tissues (P
      < 0.05). Expression of ERCC1 was closely related to clinical stage and N stage.
      The positive rate of ERCC1 was higher in III+IV or N1+N2 stage patients compared
      with I+II or N0 stage (P = 0.011, P = 0.015). We also found that 5-year survival
      of negative group of ERCC1 was remarkably higher than that of positive group by
      chi2 test (P < 0.05). Expression of ERCC1 was positively correlative to PKCalpha
      by Spearman's correlation analysis (r = 0.425, P = 0.002) in NSCLC. CONCLUSION:
      The results suggest ERCC1 and PKCalpha might be correlated with the development
      of NSCLC. ERCC1 might be related to prognosis of NSCLC. There might be existed a
      mechanism of coordination or regulation between ERCC1 and PKCalpha.

PMID- 20673528
TI  - [A case report of carina and right main bronchus resection and reconstruction
      with left thoracic incision].

PMID- 20673529
TI  - Severe cutaneous interface drug eruption associated with bendamustine.
AB  - Bendamustine is an anti-neoplastic agent approved by the FDA in 2008 for use as
      monotherapy or in combination with other agents to treat chronic lymphocytic
      leukemia (CLL) and progressed indolent B-cell non-Hodgkin lymphoma (NHL). In
      clinical trials and post-marketing safety reports administration of bendamustine
      with drugs that have known adverse reactions (i.e., allopurinol, rituximab) has
      been associated with rash, toxic skin reactions, and bullous exanthems. Here, we
      describe a patient with NHL who developed a severe cutaneous reaction associated
      with the administration of bendamustine. The severity of this drug eruption
      identifies an important adverse reaction with this drug and a potential cause for
      patient morbidity.

PMID- 20673530
TI  - Penicillium marneffei infection in an African man.
AB  - Penicilliosis is a systemic fungal infection caused by Penicillium marneffei. The
      infection is most commonly seen in Southeast Asia, Southern China, Hong Kong, and
      Taiwan. It is rarely seen among individuals of African descent. Here, we report a
      case of penicilliosis in an African man from Namibia who was studying in
      Malaysia. He presented with multiple umbilicated papules associated with cough,
      fever, loss of appetite, and weight. He also had urethral discharge and admitted
      to unprotected sexual intercourse with multiple partners. Histopathological
      examination of a skin papule showed the presence of multiple 2 to 4 microm
      intracellular yeast cells. Culture of the papule revealed Penicillium marneffei.
      The serology for human immunodeficiency virus (HIV) was positive. This case
      illustrates the need to recognize penicilliosis in any individuals staying or
      travelling to Southeast Asia and the need to look for underlying HIV infection in
      adults with umbilicated papules.

PMID- 20673531
TI  - Mycobacterium haemophilum: Cutanoeus nodules in a renal transplant patient.
AB  - A 52-year-old male with a history of renal transplantation and chronic iatrogenic
      immunosuppression presented with a several-week history of hyperpigmented
      cutaneous nodules on bilateral upper and lower extremities. Biopsy showed
      inflammatory granulomatous dermatitis caused by acid-fast bacilli (AFB). However,
      tissue cultures for mycobacterium were repeatedly negative. The patient was
      diagnosed with Mycobacterium haemophilum based on PCR results and was placed on
      empiric antibiotic therapy.

PMID- 20673532
TI  - Acroangiodermatitis of Mali in a patient with congenital myopathy.
AB  - Pseudo-Kaposi sarcoma is a disease entity that encompasses acroangiodermatitis as
      well as Steward-Bluefarb syndrome. It has varied etiologies and clinical
      presentations. Most important distinction is from Kaposi sarcoma and this is
      mainly histopathological. Here we report a case of acroangiodermatitis in a
      patient with congenital myopathy and have also discussed its pathogenesis.

PMID- 20673533
TI  - Prominent Degos-like skin lesions in a patient with chronic cutaneous lupus
      erythematosus.
AB  - Malignant atrophic papulosis, commonly known as Degos disease, is a rare
      vasculopathy encompassing both benign, cutaneous and lethal systemic variants. We
      report a case of chronic cutaneous lupus erythematosus in a 41-year-old male
      presenting with prominent Degos-like skin lesions. Multiple atrophic, porcelain
      white, scar-like papules and plaques with dusky, erythematous borders, suggestive
      of malignant atrophic papulosis, were noted on the patient's back. Additional
      cutaneous findings included photo-distributed facial erythema and discoid lupus
      like plaques on the face, shoulders, and arms. Clinicopathological correlation
      supported a diagnosis of chronic cutaneous lupus erythematosus;
      hydroxychloroquine was initiated with good clinical response. No new or active
      lesions were observed at the sixteen-month follow-up. This case highlights a rare
      skin finding associated with chronic cutaneous lupus erythematosus and
      underscores the importance of ruling out primary autoimmune disease, particularly
      lupus, before a diagnosis of malignant atrophic papulosis can be made.

PMID- 20673534
TI  - A principal case of multiple lymphoid collision tumors involving both B-cell
      chronic lymphocytic leukemia and metastatic malignant melanoma.
AB  - B-cell chronic lymphocytic leukemia/small lymphocytic B-cell lymphoma (CLL/B-SLL)
      is a neoplasm of B-cell lymphocytes that occurs frequently in the older
      population as an asymptomatic elevation of the white blood cell count (WBC) and
      has a good overall prognosis. Malignant melanoma of the skin is a neoplasm
      derived from cutaneous melanocytes that frequently arises among the elderly and,
      depending on certain histopathologic features, may metastasize loco-regionally or
      distally. However, only one report describes synchronous presentation of these
      two malignancies within the same lymph node. In this report, we present the
      unique case of an 87-year-old male with a presumed history of indolent CLL/B-SLL,
      in which metastatic malignant melanoma and CLL/B-SLL both involved 112 of 145
      dissected regional lymph nodes. Possible explanations regarding the mechanisms
      that can lead to this rare presentation of both CLL/B-SLL and melanoma in the
      same lymph nodes are discussed.

PMID- 20673535
TI  - Aquagenic wrinkling of the palms: A case report and literature review.
AB  - Aquagenic wrinkling of the palms (AWP) is a condition that results in pain and
      edema of the hands after exposure to water. We describe a 32-year-old woman who
      presented with a several-year history of AWP. She was unable to tolerate a 20
      percent aluminum chloride solution because of irritation, but a gel formulation
      of 15 percent aluminum chloride controlled her symptoms without side effects.

PMID- 20673536
TI  - Successful treatment of hand and foot psoriasis with infliximab.
AB  - Hand and foot psoriasis is a disabling condition associated with significant
      quality-of-life issues. It is characterized by hyperkeratosis and/or the
      development of recurrent crops of sterile pustules with associated erythema,
      fissuring, and scaling symmetrically localized on palm and soles. Systemic
      conventional therapies include retinoids, psoralen-UVA (PUVA), methotrexate, and
      cyclosporine. So far, only limited evidence supports the use of TNF-alfa
      blockers. Because there are reports of paradoxical induction of pustular
      psoriasis following the use or withdrawal of infliximab as well as other TNF
      inhibitors, the use of these agents in palmoplantar psoriasis has been cautioned.
      The authors describe the clinical characteristics and evolution of 4 adult
      patients with severe palmoplantar psoriasis who were treated successfully with
      infliximab. Patient data is available for a minimum of 10 months and as many as
      16. One of them with concomitant HCV infection showed no increased viral
      replication or progression of liver disease for a follow-up of 10 months;
      afterwards infliximab was stopped because of an infusion-related urticaria. All
      other patients displayed a good clinical response (> or =PPPASI 50) and were
      still receiving this regimen at last observation. This report provides
      preliminary evidence to support a cautious use of infliximab in patients with
      palmoplantar psoriasis.

PMID- 20673537
TI  - Retention mucocele on the lower lip associated with inadequate use of pacifier.
AB  - Mucocele forms because of salivary gland mucous extravasation or retention and is
      usually related to trauma in the area of the lower lips. Ruptured ducts release
      the mucous that accumulates into adjacent tissues, leading to swelling. This
      report describes a large mucocele involving the lower lip, which was produced in
      a child by incorrect use of a pacifier. A few important concepts are discussed to
      help clinicians in the diagnosis and treatment of this pathology.

PMID- 20673538
TI  - Dyshidrosiform Pemphigus vulgaris: Report of an unusual case.
AB  - Dyshidrosiform Bullous pemphigoid is a well-known entity, but dyshidrosiform
      pemphigus vulgaris has rarely been described. Our patient, a 36-year-old female,
      with a known case of pemphigus vulgaris (PV) for the last 6 years, presented with
      a 3 month history of a dyshidrosiform eruption of the soles. On the basis of
      histopathological and direct immunofluorence (DIF) findings, the new eruption was
      diagnosed as PV. We report our case as dyshidrosiform pemphigus vulgaris.

PMID- 20673539
TI  - [Linear lichen planopilaris of the face].
AB  - Linear lichen planopilaris of the face is a rare variant of lichen plano-
      pilaris. Asymptomatic follicular papules in a linear configuration are the
      characteristic clinical features. The incidence is still unknown, but there are a
      few cases reported exclusively in male adults. We present the case of a fourteen
      year-old girl with linear lichen planopilaris of the face. Improvement was
      obtained with the use of tacrolimus 0.03 percent ointment.

PMID- 20673540
TI  - Nevus lipomatosus cutaneous superficialis: An unusual presentation.
AB  - Nevus lipomatosus cutaneous superficialis (NLCS) is an uncommon benign
      hamartomatous condition characterized by the presence of mature ectopic
      adiopocytes in the dermis. Clinically they are classified into two forms. The
      classical form is characterized by groups of multiple, non-tender, soft,
      pedunculated, cerebriform, yellowish or skin-colored papules, nodules, or
      plaques. The other form of NLCS clinically manifests as a solitary dome-shaped or
      sessile papule. The classical NLCS is mostly reported to involve the pelvic or
      gluteal region. We report here a case of adult-onset classical NLCS on the pinna
      because of its rarity and unusual location. In addition, our patient also had
      some rare features of NLCS, such as onset in the latter part of life, presence of
      foul-smelling discharge, and comedo-like plugs on the lesions.

PMID- 20673541
TI  - A misdiagnosed nail bed melanoma.
AB  - Nail bed melanoma or subungual melanoma is frequently misdiagnosed compared to
      other melanoma in other anatomic sites. We report the case of a 48-year-old woman
      presenting with a dystrophic and pigmented lesion of her fourth finger nail. This
      initial presentation had been mistaken for onychomycosis, but biopsy of nail bed
      and nail matrix confirmed nail bed melanoma. This case is presented to help
      increase the awareness of atypical presentations of acral melanoma.

PMID- 20673542
TI  - Erythematous plaques on the face, trunk, and upper arms.
AB  - An 18-year-old woman presented with a one-year history of erythematous to
      slightly violaceous indurated papules and plaques on the face, earlobes, neck,
      upper arms, chest, and upper back.

PMID- 20673543
TI  - A congenital, erythematous eruption.
AB  - A 2-day-old male patient born full-term via uncomplicated vaginal delivery was
      seen for multiple erythematous, scaly papules that were present at birth.
      Physical examination showed a well-appearing male with erythematous papules with
      scale on his scalp, face, trunk, and bilateral upper and lower extremities. A 4
      mm punch biopsy was performed on one of the representative papules on his abdomen
      and subsequent histopathological tests showed multiple Langerhans cells in the
      papillary dermis with positive CD1a and Langerin stains. There was no
      extracutaneous involvement. A diagnosis of congenital self-healing Langerhans
      cell histiocytosis was made.

PMID- 20673544
TI  - Annular lesions on the lower limbs of young female.

PMID- 20673545
TI  - Prevalence and treatment outcome in anxious versus nonanxious depression: results
      from the German Algorithm Project.
AB  - OBJECTIVE: The objective of this study was to explore the prevalence of anxious
      depression in an inpatient population, to describe its clinical and
      sociodemographic correlates, and to compare treatment outcomes between patients
      with anxious and nonanxious depression. Furthermore, the efficacy of algorithm
      guided treatment versus treatment as usual in patients with anxious versus
      nonanxious depression was evaluated. METHOD: Data were collected on 429
      inpatients with the diagnosis of a depressive episode (according to ICD-10) and a
      score of >= or = 15 on the 21-item Hamilton Depression Rating Scale (HDRS-21).
      The German Algorithm Project, phase 3 (GAP3), was conducted between 2000 and 2005
      in 10 psychiatric departments throughout Germany. A baseline HDRS-21
      anxiety/somatization factor score of >= or = 7 was considered indicative of
      anxious depression. Remission was defined as an HDRS-21 score or <= = 9. To
      evaluate the efficacy of algorithm-guided treatment, patients were randomly
      assigned into 3 groups: 2 different treatment algorithms or treatment as usual.
      RESULTS: The prevalence of anxious depression was 49%. Patients with anxious
      depression were more likely than those with nonanxious depression to be older
      (mean +/- SD = 45.3 +/- 12.8 vs 42.9 +/- 12.0 years, odds ratio [OR] = 1.02 [95%
      CI, 1.00-1.03], P = .046), retired (70% vs 30%, OR = 3.09 [95% CI, 1.70-5.62], P
      = .000), without school qualification (74% vs 26%, OR = 3.11 [95% CI, 1.09-8.83],
      P = .035), more severely depressed (mean +/- SD HDRS-21 score = 20.1 +/- 5.0 vs
      18.5 +/- 4.4, OR = 1.08 [95% CI, 1.03-1.12], P = .001), and more likely to have a
      longer duration of the current episode (mean +/- SD = 20.9 +/- 26.2 vs 13.7 +/-
      14.3 weeks, OR = 1.02 [95% CI, 1.01-1.03], P = .011). Patients with anxious
      depression were more likely to display a variety of melancholic features. In
      patients with anxious depression compared to those with nonanxious depression,
      remission was less likely to be achieved (48.6% vs 61.5%, OR = 0.63 [95% CI, 0.42
      0.92], P = .018) and took longer to occur (mean +/- SD = 44 +/- 3.4 vs 30 +/- 2.8
      days, HR = 0.65 [95% CI, 0.50-0.85], P = .001). There was no significant
      interaction with the treatment mode with regard to remission (Wald = 0.20, P =
      .890). CONCLUSIONS: Anxious depression is common in patients diagnosed with
      depression. The poorer treatment outcome in patients with anxious depression
      demonstrates the need to address the issue of specific treatment strategies for
      this subgroup. However, anxious depression has no moderating effect on the
      efficacy of algorithm-guided treatment. TRIAL REGISTRATION:
      http://www.germanctr.de/ Identifier: DRKS00000161.

PMID- 20673546
TI  - McLean-Harvard International First-Episode Project: two-year stability of ICD-10
      diagnoses in 500 first-episode psychotic disorder patients.
AB  - OBJECTIVE: Because clinical and biologic research and optimal clinical practice
      require stability of diagnoses over time, we determined stability of ICD-10
      psychotic disorder diagnoses and sought predictors of diagnostic instability.
      METHOD: Patients from the McLean-Harvard International First-Episode Project,
      conducted from 1989 to 2003, who were hospitalized for first psychotic illnesses
      (N = 500) were diagnosed by ICD-10 criteria at baseline and 24 months, on the
      basis of extensive prospective assessments, to evaluate the longitudinal
      stability of specific categorical diagnoses and predictors of diagnostic change.
      RESULTS: Diagnostic stability averaged 90.4%, ranking as follows: schizoaffective
      disorder (100.0%) > mania with psychosis (99.0%) > mixed affective episode
      (94.9%) > schizophrenia (94.6%) > delusional disorder (88.2%) > severe depressive
      episode with psychotic symptoms (85.2%) > acute psychosis with/without
      schizophrenia symptoms = unspecified psychosis (all 66.7%) >> acute schizophrenia
      like psychosis (28.6%). Diagnoses changed by 24 months of follow-up to
      schizoaffective disorder (37.5%), bipolar disorder (25.0%), schizophrenia
      (16.7%), or unspecified nonorganic psychosis (8.3%), mainly through emerging
      affective features. By logistic regression, diagnostic change was associated with
      Schneiderian first-rank psychotic symptoms at intake > lack of premorbid
      substance use. CONCLUSIONS: We found some psychotic disorder diagnoses to be more
      stable by ICD-10 than DSM-IV criteria in the same patients, with implications for
      revisions of both diagnostic systems.

PMID- 20673547
TI  - Rapid resolution of suicidal ideation after a single infusion of an N-methyl-D
      aspartate antagonist in patients with treatment-resistant major depressive
      disorder.
AB  - OBJECTIVE: Suicidal ideation is a medical emergency, especially when severe.
      Little research has been done on pharmacologic interventions that could address
      this problem. Ketamine, an N-methyl-D-asparate antagonist, has been reported to
      have antidepressant effects within hours. We examined the effects of a single
      dose of ketamine on suicidal ideation in subjects with treatment-resistant major
      depressive disorder (MDD). METHOD: Thirty-three subjects with DSM-IV-diagnosed
      MDD received a single open-label infusion of ketamine (0.5 mg/kg) and were rated
      at baseline and at 40, 80, 120, and 230 minutes postinfusion with the Scale for
      Suicide Ideation (SSI), the Montgomery-Asberg Depression Rating Scale, the
      Hamilton Depression Rating Scale, and the Beck Depression Inventory. The study
      was conducted between October 2006 and January 2009. RESULTS: Suicidal ideation
      scores decreased significantly on the SSI as well as on the suicide subscales of
      other rating instruments within 40 minutes; these decreases remained significant
      through the first 4 hours postinfusion (P < .001). Ten subjects (30%) had an SSI
      score >= 4 at baseline; all these scores dropped below 4 (9 dropped by 40 minutes
      and 1 by 80 minutes). For those patients with a starting score below 4 on the
      SSI, only 1 reached a score of 4. Depression, anxiety, and hopelessness were
      significantly improved at all time points (P < .001). CONCLUSIONS: Suicidal
      ideation in the context of MDD improved within 40 minutes of a ketamine infusion
      and remained improved for up to 4 hours postinfusion. Future studies with
      ketamine in suicidal ideation are warranted due to the potential impact on public
      health. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00088699.

PMID- 20673548
TI  - Reduced anterior cingulate and orbitofrontal volumes in child abuse-related
      complex PTSD.
AB  - OBJECTIVE: Classic posttraumatic stress disorder (PTSD) is associated with
      smaller hippocampus, amygdala, and anterior cingulate cortex (ACC) volumes. We
      investigated whether child abuse-related complex PTSD--a severe form of PTSD with
      affect dysregulation and high comorbidity--showed similar brain volume
      reductions. METHOD: We used voxel-based morphometry to measure gray matter
      concentrations in referred outpatients with child abuse-related complex PTSD (n =
      31) compared to matched healthy nontraumatized controls (n = 28). Complex PTSD
      was diagnosed using the Structured Clinical Interview for DSM-IV-TR and the
      Structured Clinical Interview for Disorders of Extreme Stress. All respondents
      were scanned on a 1.5-T magnetic resonance system at the VU Medical Center,
      Amsterdam, The Netherlands, between September 2005 and February 2006. RESULTS: As
      was hypothesized, patients with child abuse-related complex PTSD showed
      reductions in gray matter concentration in right hippocampus (P(SVC corrected) =
      .04) and right dorsal ACC (P(SVC corrected) = .02) compared to controls. In
      addition, a reduction in gray matter concentration in the right orbitofrontal
      cortex (OFC) was found. Severity of child abuse and PTSD-hyperarousal correlated
      negatively with ACC volume. Impulsivity correlated negatively with hippocampus
      volume, and anger, with hippocampus and OFC volume. Comorbidity of borderline
      personality disorder--compared to comorbid cluster C personality disorder-
      accounted for more extensive reductions in the ACC and OFC volume. CONCLUSIONS:
      In complex PTSD, not only the hippocampus and the ACC but also the OFC seem to be
      affected, even in the absence of comorbid borderline personality disorder. These
      results suggest that neural correlates of complex PTSD are more severe than those
      of classic PTSD.

PMID- 20673549
TI  - Long-acting injectable versus oral naltrexone maintenance therapy with
      psychosocial intervention for heroin dependence: a quasi-experiment.
AB  - OBJECTIVE: To conduct a quasi-experimental comparison of early clinical outcomes
      between injectable, sustained-release, depot naltrexone formulation versus oral
      naltrexone maintenance therapy in individuals with opiate dependence. METHOD:
      Early retention in treatment and urine-confirmed opiate use in the first 8 weeks
      postdetoxification were compared between patients (diagnosed as opiate-dependent
      according to DSM-IV criteria) participating in 2 concurrently run randomized
      clinical trials of oral (n = 69; patients treated from September 1999 to May
      2002) and long-acting injectable (n = 42; patients treated from November 2000 to
      June 2003) naltrexone maintenance therapy with psychosocial therapy. RESULTS:
      Long-acting injectable naltrexone produced significantly better outcome than oral
      naltrexone on days retained in treatment (F(1,106) = 6.49, P = .012) and for 1
      measure of opiate use (F(1,106) = 5.26, P = .024); other measures were not
      significantly different, but differences were in the same direction. In
      subanalyses, there were interaction effects between baseline heroin use severity
      and type of treatment. In subanalyses, heroin users with more severe baseline use
      showed better retention with oral naltrexone maintenance therapy combined with
      intensive psychotherapy (behavioral naltrexone therapy) as compared to retention
      shown by severe heroin users treated with long-acting naltrexone injections
      combined with standard cognitive-behavioral therapy (chi2(1)= 9.31, P = .002);
      less severe heroin users evidenced better outcomes when treated with long-acting
      injectable naltrexone. CONCLUSIONS: This quasi-experimental analysis provides
      tentative indications of superior outcomes for heroin-dependent patients treated
      with long-acting injectable naltrexone compared to oral naltrexone. The finding
      that heroin users with more severe baseline use achieved better outcomes with
      oral naltrexone is most probably attributable to the intensive nature of the
      psychosocial treatments provided and points to the opportunity for continued
      research in augmenting injectable naltrexone with psychosocial strategies to
      further improve outcome, especially in individuals with more severe use. The
      results should be considered exploratory given the quasi-experimental nature of
      the study.

PMID- 20673550
TI  - Two clinical trial designs to examine personalized treatments for psychiatric
      disorders.
AB  - The National Institute of Mental Health Strategic Plan calls for the development
      of personalized treatment strategies for mental disorders. In an effort to
      achieve that goal, several investigators have conducted exploratory analyses of
      randomized controlled clinical trial (RCT) data to examine the association
      between baseline subject characteristics, the putative moderators, and the
      magnitude of treatment effect sizes. Exploratory analyses are used to generate
      hypotheses, not to confirm them. For that reason, independent replication is
      needed. Here, 2 general approaches to designing confirmatory RCTs are described
      that build on the results of exploratory analyses. These approaches address
      distinct questions. For example, a 2 * 2 factorial design provides an empirical
      test of the question, "Is there a greater treatment effect for those with the
      single-nucleotide polymorphism than for those without that polymorphism?" and the
      hypothesis test involves a moderator-by-treatment interaction. In contrast, a
      main effects strategy evaluates the intervention in subgroups and involves
      separate hypothesis-testing studies of treatment for subjects with the genotypes
      hypothesized to have enhanced and adverse response. These designs require widely
      disparate sample sizes to detect a given effect size. The former could need as
      many as 4-fold the number of subjects. As such, the choice of design impacts the
      research costs, clinical trial duration, and number of subjects exposed to risk
      of an experiment, as well as the generalizability of results. When resources are
      abundant, the 2 * 2 design is the preferable approach for identifying
      personalized interventions because it directly tests the differential treatment
      effect, but its demand on research funds is extraordinary.

PMID- 20673552
TI  - Identifying depressive subtypes in a large cohort study: results from the
      Netherlands Study of Depression and Anxiety (NESDA).
AB  - OBJECTIVE: The heterogeneity of depression in the current classification system
      remains a point of discussion in the psychiatric field, despite previous efforts
      to subclassify depressive disorders. Data-driven techniques may help to come to a
      more empirically based classification. This study aimed to identify depressive
      subtypes within a large cohort of subjects with depression. METHOD: Baseline data
      from 818 persons with a DSM-IV diagnosis of current major depressive disorder or
      minor depression who participated in the Netherlands Study of Depression and
      Anxiety were used. Respondents were recruited in the community, in primary care,
      and in specialized mental health care from September 2004 through February 2007.
      Latent classes were derived from latent class analysis using 16 depressive
      symptoms from the Composite International Diagnostic Interview and the Inventory
      of Depressive Symptomatology. Classes were characterized using demographic,
      clinical psychiatric, psychosocial, and physical health descriptors. RESULTS:
      Three classes were identified: a severe melancholic class (prevalence, 46.3%), a
      severe atypical class (prevalence, 24.6%), and a class of moderate severity
      (prevalence, 29.1%). Both severe classes were characterized by more neuroticism
      (melancholic OR = 1.05 [95% CI, 1.01-1.10]; atypical OR = 1.07 [95% CI, 1.03
      1.12]), more disability (melancholic OR = 1.07 [95% CI, 1.05-1.09]; atypical OR =
      1.06 [95% CI, 1.04-1.07]), and less extraversion (melancholic OR = 0.95 [95% CI,
      0.92-0.99]; atypical OR = 0.95 [95% CI, 0.92-0.99]) than the moderate class.
      Comparing the melancholic class with the atypical class revealed that the
      melancholic class had more smokers (atypical OR = 0.57 [95% CI, 0.39-0.84]) and
      more childhood trauma (atypical OR = 0.86 [95% CI, 0.74-1.00]), whereas the
      atypical class had more women (atypical OR = 1.52 [95% CI, 0.99-2.32]), a higher
      body mass index (atypical OR = 1.13 [95% CI, 1.09-1.17]), and more metabolic
      syndrome (atypical OR = 2.17 [95% CI, 1.38-3.42]). CONCLUSIONS: Both depression
      severity (moderate vs severe) and the nature of depressive symptoms (melancholic
      vs atypical) were found to be important differentiators between subtypes. Higher
      endorsement rates of somatic symptoms and more metabolic syndrome in the atypical
      class suggest the involvement of a metabolic component.

PMID- 20673551
TI  - Suicidality and risk of suicide--definition, drug safety concerns, and a
      necessary target for drug development: a brief report.
AB  - OBJECTIVE: To address issues concerning potential treatment-emergent
      "suicidality," a consensus conference was convened March 23-24, 2009.
      PARTICIPANTS: This gathering of participants from academia, government, and
      industry brought together experts in suicide prevention, clinical trial design,
      psychometrics, pharmacoepidemiology, and genetics, as well as research
      psychiatrists involved in studies in studies of psychiatric disorders associated
      with elevated suicide risk across the life cycle. The process involved reviews of
      the relevant literature, and a series of 6 breakout sessions focused on specific
      questions of interest. EVIDENCE: Each of the participants at the meeting received
      references relevant to the formal presentations (as well as the slides for the
      presentations) for their review prior to the meeting. In addition, the assessment
      instruments of suicidal ideation/behavior were reviewed in relationship to
      standard measures of validity, reliability, and clinical utility, and these
      findings were discussed at length in relevant breakout groups, in the final
      plenary session, and in the preparation of the article. Consensus and dissenting
      views were noted. CONSENSUS PROCESS: Discussion and questions followed each
      formal presentation during the plenary sessions. Approximately 6 questions per
      breakout group were prepared in advance by members of the Steering Committee and
      each breakout group chair. Consensus in the breakout groups was achieved by
      nominal group process. Consensus recommendations and any dissent were reviewed
      for each breakout group at the final plenary session. All plenary sessions were
      recorded and transcribed by a court stenographer. Following the transcript, with
      input by each of the authors, the final paper went through 14 drafts. The output
      of the meeting was organized into this brief report and the accompanying full
      article from which it is distilled. The full article was developed by the authors
      with feedback from all participants at the meeting and represents a consensus
      view. Any areas of disagreement at the conference have been noted in the text.
      CONCLUSIONS: The term suicidality is not as clinically useful as more specific
      terminology (ideation, behavior, attempts, and suicide). Most participants
      applauded the FDA's encouragement of standard definitions and definable
      expectations for investigators and industry sponsors. Further research of
      available assessment instruments is needed to verify their utility, reliability,
      and validity in identifying suicide-associated treatment-emergent adverse effects
      and/or a signal of efficacy in suicide prevention trials. The FDA needs to
      systematically monitor postmarketing events by encouraging the development of a
      validated instrument for postmarketing surveillance of suicidal ideation,
      behavior, and risk. Over time, the FDA, industry, and clinical researchers should
      evaluate the impact of the requirement that all central nervous system clinical
      drug trials must include a Columbia Classification Algorithm of Suicide
      Assessment (C-CASA)-compatible screening instrument for assessing and documenting
      the occurrence of treatment-emergent suicidal ideation and behavior. Finally,
      patients at high risk for suicide can safely be included in clinical trials, if
      proper precautions are followed.

PMID- 20673553
TI  - A double-blind, randomized study comparing the efficacy and safety of sertindole
      and risperidone in patients with treatment-resistant schizophrenia.
AB  - OBJECTIVE: The comparative efficacy of second-generation antipsychotics has yet
      to be fully elucidated in patients with treatment-resistant schizophrenia. The
      objective of this study was to examine the efficacy and safety of sertindole,
      compared to risperidone, in this patient population. METHOD: In this multicenter,
      phase 3, randomized, double-blind, parallel-group study, only patients with DSM
      IV schizophrenia who had failed an adequate antipsychotic treatment within the
      previous 6 months and who had not responded positively to haloperidol during
      screening were eligible for enrollment. The primary efficacy variable was change
      in Positive and Negative Syndrome Scale (PANSS) from baseline to final
      assessment. Weekly assessments included the PANSS, the Brief Psychiatric Rating
      Scale (BPRS), the Scale for the Assessment of Negative Symptoms (SANS), and the
      Clinical Global Impressions (CGI) scale. The study was conducted between June
      1996 and April 1998. RESULTS: Of the 321 patients randomly assigned to double
      blind treatment, 217 patients completed the study (sertindole, n/n = 142/216
      [66%]; risperidone, n/n = 75/105 [71%]). The main reason for withdrawal in both
      groups was ineffective therapy. The between-group difference in PANSS total score
      was not statistically significant and both groups showed improvement, with mean
      changes of -18.6 in the sertindole group and -20.9 in the risperidone group based
      on observed cases and -12.0 and -19.0, respectively, based on the last
      observation-carried-forward method for inputing missing data. There were no
      statistically significant differences between the groups in any of the secondary
      end points: PANSS positive and negative subscales, CGI scores, BPRS total scores
      and positive symptom subscale scores, and SANS total scores. Patients reported
      similar levels of adverse events and treatment-emergent adverse events (TEAEs),
      except for extrapyramidal syndrome-related TEAEs, which were more common in the
      risperidone-treated group. Prolongation of the QTc interval was observed
      significantly more frequently with sertindole treatment. CONCLUSIONS: Sertindole
      and risperidone are effective and well-tolerated in patients with treatment
      resistant schizophrenia. Sertindole offers an alternative treatment option for
      refractory patients in Europe given its good EPS profile, favorable metabolic
      profile, and comparable efficacy to risperidone.

PMID- 20673554
TI  - Adjunctive armodafinil for major depressive episodes associated with bipolar I
      disorder: a randomized, multicenter, double-blind, placebo-controlled, proof-of
      concept study.
AB  - OBJECTIVE: To evaluate the efficacy and safety of armodafinil, the longer-lasting
      isomer of modafinil, when used adjunctively in patients with bipolar depression.
      METHOD: In this 8-week, multicenter, randomized, double-blind, placebo-controlled
      study conducted between June 2007 and December 2008, patients who were
      experiencing a major depressive episode associated with bipolar I disorder
      (according to DSM-IV-TR criteria) despite treatment with lithium, olanzapine, or
      valproic acid were randomly assigned to adjunctive armodafinil 150 mg/d (n = 128)
      or placebo (n = 129) administered once daily in the morning. The primary outcome
      measure was change from baseline in the total 30-item Inventory of Depressive
      Symptomatology, Clinician-Rated (IDS-C30) score. Secondary outcomes included
      changes from baseline in scores on the Montgomery-Asberg Depression Rating Scale,
      among other psychological symptom scales. Statistical analyses were performed
      using analysis of covariance (ANCOVA), with study drug and concurrent mood
      stabilizer treatment for bipolar disorder as factors and the corresponding
      baseline value as a covariate. A prespecified sensitivity analysis was done using
      analysis of variance (ANOVA) if a statistically significant treatment-by-baseline
      interaction was found. Tolerability was also assessed. RESULTS: A significant
      baseline-by-treatment interaction in the total IDS-C30 score (P = .08) was found.
      Patients administered adjunctive armodafinil showed greater improvement in
      depressive symptoms as seen in the greater mean +/- SD change on the total IDS
      C30 score (-15.8 +/- 11.57) compared with the placebo group (-12.8 +/- 12.54)
      (ANOVA: P = .044; ANCOVA: P = .074). No differences between treatment groups were
      observed in secondary outcomes. Adverse events reported more frequently in
      patients receiving adjunctive armodafinil were headache, diarrhea, and insomnia.
      Armodafinil was not associated with an increased incidence and/or severity of
      suicidality, depression, or mania or with changes in metabolic profile
      measurements. CONCLUSIONS: In this proof-of-concept study, adjunctive armodafinil
      150 mg/d appeared to improve depressive symptoms according to some, but not all,
      measures and was generally well tolerated in patients with bipolar depression.
      TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00481195.

PMID- 20673555
TI  - Shared neural activity in panic disorder and undifferentiated somatoform disorder
      compared with healthy controls.
AB  - OBJECTIVE: In previous studies, some brain areas, including parahippocampal
      gyrus, were suggested to be associated with panic disorder. Both panic disorder
      and somatoform disorders are associated with anxiety. This study sought to
      determine if there are shared neural activity underlying panic disorder and
      undifferentiated somatoform disorder. METHOD: Sixteen nonmedicated patients with
      panic disorder, 16 nonmedicated patients with undifferentiated somatoform
      disorder, and 10 healthy subjects were scanned between February 2005 and August
      2006. Diagnoses were made according to the Korean version of the Structured
      Clinical Interview for DSM-IV Axis I Disorders, Research Version, Patient/Non
      Patient Edition. Regional cerebral perfusion was measured by 99 m-Tc-ethyl
      cysteinate dimer single photon emission computed tomography (SPECT). Using
      statistical parametric mapping analysis, we compared the SPECT images between the
      groups. RESULTS: Significant hyperperfusion was found at the left superior
      temporal gyrus and the left supramarginal gyrus in the panic disorder patients
      when compared to the controls (family-wise error [FWE], P < .001). The somatoform
      disorder patients showed hyperperfusion in the left hemisphere at the superior
      temporal gyrus, inferior parietal lobule, middle occipital gyrus, precentral
      gyrus, postcentral gyrus, and, in the right hemisphere, at the superior temporal
      gyrus when compared to the controls (false discovery rate [FDR], P < .001). In
      contrast, significant hypoperfusion was found at the right parahippocampal gyrus
      in each of panic disorder (FWE, P = .001) and somatoform disorder (FWE, P < .001)
      groups compared to healthy controls. However, no significant differences were
      found in regional cerebral perfusion between the 2 disorder groups. CONCLUSIONS:
      Both panic disorder and undifferentiated somatoform disorder showed
      hyperperfusion in the left superior temporal gyrus and hypoperfusion in the right
      parahippocampal gyrus, which suggests that the 2 disorders are likely to share
      neural activity.

PMID- 20673557
TI  - Effects of atomoxetine with and without behavior therapy on the school and home
      functioning of children with attention-deficit/hyperactivity disorder.
AB  - OBJECTIVE: To evaluate the effects of atomoxetine alone and in combination with
      behavior therapy on the school functioning of children with attention
      deficit/hyperactivity disorder (ADHD). Most atomoxetine studies have not assessed
      school functioning other than by measuring the change in ADHD symptoms. Combining
      behavior therapy with atomoxetine may be particularly beneficial for the academic
      domain as medication has not been found to produce sustained benefits in this
      realm. However, there is little research examining the effects of combining
      atomoxetine and behavior therapy. METHOD: In an 8-week open-label trial, 56
      children aged 6-12 years with ADHD diagnosed according to DSM-IV-TR were randomly
      assigned to receive atomoxetine and behavior therapy or atomoxetine alone.
      Behavior therapy consisted of an 8-week parenting course, a child social skills
      course, and a teacher-implemented daily report card of classroom behavior. The
      primary outcome was direct observation of the subject's classroom behavior.
      Secondary outcomes included change in ADHD symptoms and functioning at home and
      school. All data were collected between March 2007 and May 2008. RESULTS:
      Classroom observations showed that atomoxetine decreased rule violations (P <
      .0001). Moreover, atomoxetine was associated with significant improvements in
      ADHD and oppositional defiant disorder symptoms at home and school and enhanced
      functioning in both domains (Impairment Rating Scale: all P < .001). Combined
      treatment led to greater improvements in parent-rated symptoms of inattention (P
      < .01), problem behaviors (P < .001), and academic impairment (P < .05). However,
      teachers did not report significant group differences. CONCLUSIONS: Atomoxetine
      improved ADHD symptoms and classroom functioning as measured by parents,
      teachers, and direct observation. The addition of behavior therapy led to further
      improvements at home but not at school. TRIAL REGISTRATION: clinicaltrials.gov
      Identifier: NCT00918567.

PMID- 20673556
TI  - Fluoxetine treatment of alcoholic perpetrators of domestic violence: a 12-week,
      double-blind, randomized, placebo-controlled intervention study.
AB  - OBJECTIVE: Behaviorally based therapies for the treatment of perpetrators who
      initiate intimate partner violence (IPV) have generally shown minimal therapeutic
      efficacy. To explore a new treatment approach for IPV, we examined the effects of
      a selective serotonin reuptake inhibitor on the irritability subscale score of
      the Modified Overt Aggression Scale. This score served as a surrogate marker for
      the anger and physical aggression that characterize perpetrators of IPV. METHOD:
      A 12-week, double-blind, randomized, placebo-controlled intervention study
      employing fluoxetine, alcohol treatment, and cognitive-behavioral therapy was
      performed. Sixty (46 men) non-court-mandated, DSM-IV-diagnosed alcoholic
      perpetrators of IPV with a history of at least 2 episodes of IPV in the year
      prior to participation in the study were evaluated. The primary outcome measure
      was the score on the irritability subscale of the Modified Overt Aggression
      Scale. Secondary measures included anxiety, depression, and ratings by the
      perpetrator's spouse/significant other. The study was conducted from January 2002
      through December 2007. RESULTS: A repeated-measures analysis of variance using
      the irritability subscale scores obtained from perpetrators who completed the 12
      week study (n = 24) showed a significant drug effect (F(1,21) = 12.09, P = .002).
      Last observation carried forward (F(1,32) = 4.24, P = .048) as well as intent-to
      treat analysis (F(1,54) = 5.0, P = .034) also showed a significant drug effect.
      Spouses'/significant others' physical and nonphysical Partner Abuse Scale ratings
      showed a significant reduction of abuse over time (F(1,11) = 10.2, P = .009 and
      F(1,11) = 24.2, P = .0005, respectively). CONCLUSION: This is the first
      controlled study to show that a pharmacologic intervention employing a selective
      serotonin reuptake inhibitor, in conjunction with alcohol treatment and cognitive
      behavioral therapy, can reduce measures of anger and physical aggression in
      alcoholic perpetrators of IPV.

PMID- 20673558
TI  - Antipsychotic medication and oxidative cell stress: a systematic review.
AB  - OBJECTIVE: To look at (1) the association between antipsychotics and cell stress,
      (2) whether first-generation antipsychotics may show different effects than
      second-generation antipsychotics, and (3) whether recommendations can be made
      regarding medication. DATA SOURCES: We conducted a systematic review of 5
      databases for all articles published until December 31, 2007: PubMed, Ovid
      MEDLINE, EMBASE, PsycINFO, and EBM Reviews. Under specific headings (eg, "heat
      shock proteins" and "oxidative stress"), a systematic search of these databases
      included such terms as HSP70 and homocysteine, and specific search strings were
      constructed. No limits were placed on the year or language of publication.
      References from pertinent articles or books were retrieved. STUDY SELECTION: We
      included 42 articles of human studies from 2,387 references originally retrieved.
      We included only articles that (1) were quantitative; (2) referred only to human
      tissue, in vivo, or in vitro; (3) stated what tissue was examined; (4) identified
      what metabolites were measured; and (5) had references. DATA EXTRACTION: All
      articles were assessed by 2 authors, which ensured that the inclusion criteria
      were met. The selected studies were too heterogeneous to be combined for any
      useful meta-analysis. Three authors, therefore, independently interpreted the
      data, using specified criteria to judge whether each study showed a beneficial,
      detrimental, or no effect on the markers measured. DATA SYNTHESIS: The analysis
      revealed no conclusive association with direct or indirect markers of oxidative
      cell stress and antipsychotics. For every reviewed antipsychotic, we revealed
      differing research results showing a beneficial, detrimental, or no effect. This
      was true for in vivo as well as in vitro studies. CONCLUSIONS: It remains unclear
      whether antipsychotics increase or reduce cell stress. Claims of neuroprotective
      properties of antipsychotics seem premature.

PMID- 20673560
TI  - Subsyndromal depressive symptoms after symptomatic recovery from mania are
      associated with delayed functional recovery.
AB  - OBJECTIVE: This study examined whether the presence of subsyndromal depressive
      symptoms predicted functional recovery after an acute manic episode. METHOD:
      Subjects with bipolar I disorder (according to the Structured Clinical Interview
      for DSM-IV) who, at the time of symptomatic recovery from an acute manic or
      hypomanic episode, had a concomitant functional recovery (n = 52) were compared
      on demographic variables and mood symptoms to those who had symptomatically
      recovered but not functionally recovered (n = 33). Demographic and mood variables
      were examined in the nonfunctionally recovered group to assess predictors of time
      to functional recovery. The primary functional outcome measure used was the Life
      Functioning Questionnaire, a 5-minute, gender-neutral self-report scale to
      measure role function in 4 domains: workplace, duties at home, leisure time with
      family, and leisure time with friends. Participants in the study were recruited
      from July 2000 through February 2005. RESULTS: Depressive symptoms, even at a
      subsyndromal level, were significantly associated with persisting functional
      impairment after symptomatic recovery from a manic episode (P < .02).
      Subsyndromal depressive symptoms also significantly predicted a slower time to
      functional recovery over the next 9 months (P = .006). CONCLUSION: The presence
      of even mild subsyndromal depressive symptoms may interfere with functional
      recovery in patients with bipolar disorder after symptomatic recovery from a
      manic or hypomanic episode.

PMID- 20673561
TI  - Evaluation of Interleukin-18 as a Non Invasive Marker of Liver Fibrosis among
      Chronic Hepatitis C Virus Patients.
AB  - BACKGROUND: The World Health Organization has declared hepatitis C a global
      health problem, with approximately 3% of the world's population (roughly 170-200
      million people) infected with hepatitis C virus (HCV). In Egypt, Chronic
      hepatitis C is the main cause of liver cirrhosis and liver cancer. Liver biopsy
      is currently the gold standard method for ascertaining the presence of cirrhosis,
      and scoring the severity of necroinflammation and fibrosis, but it is invasive,
      expensive and associated with rare but serious complications. There has been
      increasing interest in noninvasive assessment of liver fibrosis by the use of
      surrogate serum markers; one of them is interleukin-18 (IL-18). OBJECTIVES: The
      aim of this study was the estimation of the levels of interleukin-18 in chronic
      hepatitis C patients and comparing between IL-18 levels and results of liver
      biopsy, aspartate aminotransferase (AST) and alanine aminotransferase (ALT)
      levels. MATERIAL AND METHODS: It included fifty chronic viral hepatitis C
      patients who were subjected to liver biopsy as well as fifty healthy blood donors
      as a control group. Sera were tested for estimation of ALT and AST levels and
      were subjected to enzyme-linked immunosorbent assay (ELISA) for determination of
      IL-18 levels. RESULTS: The mean level of IL-18 was significantly higher in
      chronic hepatitis C patients (347.22pg/ml) compared to the controls
      (209.61pg/ml), and there was significant relation between levels of IL-18 and the
      stage of liver fibrosis. CONCLUSION: IL-18 could be used as an additional non
      invasive marker for monitoring the degree of liver fibrosis in chronic hepatitis
      C patients.

PMID- 20673559
TI  - Relapse prevention in first-episode schizophrenia--maintenance vs intermittent
      drug treatment with prodrome-based early intervention: results of a randomized
      controlled trial within the German Research Network on Schizophrenia.
AB  - OBJECTIVE: After acute treatment of the first illness episode in schizophrenia,
      antipsychotic maintenance treatment is recommended for at least 1 year. Evidence
      for the optimal subsequent treatment is still scarce. Targeted intermittent
      treatment was found to be less effective than continuous treatment at preventing
      relapse in multiple episode patients; however, a post hoc analysis of our own
      data from a previous study suggested comparable efficacy of the 2 treatment
      approaches in first-episode patients. The current study was therefore designed to
      compare prospectively the relapse preventive efficacy of further maintenance
      treatment and targeted intermittent treatment in patients with ICD-10-diagnosed
      first-episode schizophrenia. METHOD: A randomized controlled trial was conducted
      within the German Research Network on Schizophrenia. Entry screening took place
      between November 2000 and May 2004. After 1 year of antipsychotic maintenance
      treatment, stable first-episode patients were randomly assigned to 12 months of
      further maintenance treatment or stepwise drug discontinuation and targeted
      intermittent treatment. In case of prodromal symptoms of an impending relapse,
      patients in both groups received early drug intervention, guided by a decision
      algorithm. The primary outcome measure was relapse (increase in the Positive and
      Negative Syndrome Scale positive score > 10, Clinical Global Impressions-Change
      score >= 6, and decrease in Global Assessment of Functioning score > 20 between 2
      visits). RESULTS: Of 96 first-episode patients, only 44 were eligible for the
      assigned treatment (maintenance treatment, n = 23; intermittent treatment, n =
      21). The rates of relapse (19% vs 0%; P = .04) and deterioration (up to 57% vs
      4%; P < .001) were significantly higher in the intermittent treatment group than
      in the maintenance treatment group, but quality-of-life scores were comparable.
      Intermittent treatment patients received a significantly lower amount of
      antipsychotics (in haloperidol equivalents; P < .001) and tended to show fewer
      side effects, particularly extrapyramidal side effects. CONCLUSIONS: Maintenance
      treatment is more effective than targeted intermittent treatment in preventing
      relapse, even in stable first-episode patients after 1 year of maintenance
      treatment, and should be the preferred treatment option. However, about 50% of
      patients remain stable at a significantly lower drug dose and show fewer side
      effects, and a substantial proportion refuse maintenance treatment. Alternative
      long-term treatment strategies, including targeted intermittent treatment, should
      therefore be provided in individual cases. TRIAL REGISTRATION: clinicaltrials.gov
      Identifier: NCT00159120.

PMID- 20673562
TI  - Statistical process control for cancelled operations at the paediatric surgery
      department of a university hospital.
AB  - BACKGROUND: Being a cause of delayed patient management and underutilization of
      resources, cancelled operations are considered a low quality service. Moreover,
      anticipation of surgery is stressful for both patients and families, particularly
      if the patient is a child; additional anxiety posed by last-minute cancellation
      is, therefore, of primary concern. OBJECTIVES: The present study was done to
      estimate the rate and explore the determinant causes of cancellation of planned
      operations on the day of surgery at the paediatric surgery department of a
      university hospital in Alexandria. METHODS: A cross sectional study was
      performed, interviewing some paediatric surgeons and anaesthesiologists
      practising at the hospital to collect in depth information about causes of
      cancelled operations, in addition to revising daily operation sheets for 181
      operations to calculate cancellation rate and causes of cancelled operations. To
      Study patterns of variation in cancellation rate, a control chart (p-chart) was
      drawn. RESULTS: The overall cancellation rate was almost 25%. Analysis of the
      control chart showed an average cancellation rate of 25%, upper control limit of
      74% and a Lower control limit of zero. Of the cancelled operations, 64.4% were of
      avoidable causes. Pareto chart showed that not being fit for anaesthesia either
      for electrolyte disturbances, low haemoglobin level or fever was the commonest
      reason for cancellation of operation, followed by patient having chest infection
      and patient or doctors not showing on the day of operation (those formed more
      than 85% of causes). CONCLUSION AND RECOMMENDATIONS: Implementation of outpatient
      preoperative assessment and preparation for surgery, in addition to the
      improvement of communication between patient, doctors and nurses are highly
      recommended.

PMID- 20673563
TI  - Improvement of knowledge, attitudes and practices of health care workers towards
      the transmission of blood-borne pathogens: an intervention study.
AB  - BACKGROUND: Health care workers (HCW) are at risk of occupational infection with
      blood-borne pathogens (BBP). AIM OF THE STUDY: 1) to assess the knowledge,
      attitude and practice (KAP) of nurses, lab technicians and housekeepers working
      in nine Primary Health Care centers in Cairo and Giza governorates in Egypt
      concerning BBP; 2) to apply a health education intervention on BBP; 3) to assess
      the effectiveness of the health education intervention on the level of KAP of the
      study population. METHODS: A total of 130 study participants were enrolled and
      received the health education intervention, only 86 participants came back for
      the post-intervention evaluation (drop-out rate = 33.8%). RESULTS: It was found
      that 34% of participants were exposed to one or more needle stick injuries during
      the 3 months preceding the intervention, and only 13.8% received the hepatitis B
      immunization. Comparison of the pre- and post-intervention scores for the total
      study population showed a significant increase in the post-intervention
      cumulative KAP score, as well as the knowledge, attitude and practice scores by
      about 13, 12, 11 and 20% respectively (p<0.001). The housekeepers, compared to
      nurses and lab technicians, were the best recipients to the health education
      intervention with a significantly higher percent change of the KAP score (27.7,
      16.9 and 9.5% respectively, p=0.005). Reasons for non-compliance to the
      application of preventive measures to protect against BBP were lack of resources,
      work overload and lack of training. CONCLUSION AND RECOMMENDATIONS: Continuous
      education and in-service training on prevention of BBP transmission is mandatory
      to protect HCW.

PMID- 20673564
TI  - Flow cytometry for cell cycle parameters in healthcare workers potentially
      exposed to ionizing radiation.
AB  - INTRODUCTION: There is much controversy about the effects of chronic low dose
      exposure to ionizing radiation and the possible consequences particularly in
      occupational exposures. OBJECTIVES: This study aims at the assessment of cell
      cycle in healthcare workers (HCWs) occupationally exposed to radiation. Subjects
      and Methods. Participants in the study included 106 HCWs, of them 79 were
      potentially exposed to ionizing radiation during their routine work, while the
      other 27 were non-exposed subjects taken as controls. Exposure was monitored by
      thermo-luminescent dosimeters. Peripheral blood lymphocytes were separated, fixed
      and stained with propidium iodide followed by analysis via flow cytometry for DNA
      content as a marker of cell cycle and apoptosis pattern. RESULTS: Compared to
      controls, exposed subjects showed a significant higher mean percentage of G2/M
      cell (4.01+/-4.19 vs. 1.88+/-3.02, p<0.05) and higher mean percentage of
      coefficient of variation (CV) (4.41+/-1.37 vs. 3.81+/-1.07, p<0.05). Furthermore,
      HCWs with older age, longer duration of exposure and higher cumulative radiation
      dose had significant higher G2/M % and CV% with lower G0/G1 % than other workers.
      Significant correlation was found between cumulative dose of radiations and the
      mean percentage of cells in the phases of G0/G1 and G2/M as well as their mean
      CV% (p<0.05). CONCLUSION AND RECOMMENDATIONS: Healthcare workers exposed to
      radiation had cellular changes that could be detected by flow cytometry that
      probably can be used as a follow up marker for potential major harmful effects.

PMID- 20673565
TI  - Quality of diabetes care in family health facilities in one health district in
      alexandria.
AB  - BACKGROUND: The aim of the present study was to evaluate the quality of service
      provided to type 2 diabetes in family health facilities in one Health District in
      Alexandria governorate. Also, the study aimed at assessing the difference in the
      quality of diabetes care between family health units and family health centers.
      MATERIAL AND METHODS: Records of 384 diabetic patients in 6 family health units
      and 3 family health centers were reviewed to abstract variables used to compute
      process and outcome performance measures for diabetes care. RESULTS: The level of
      performing process of care measures varied between individual measures with
      microalbuminuria testing done for 1.3% of the sample while smoking cessation
      counseling was done for all smokers. All measures were performed in family health
      centers in higher or equal percentage to family health units. Out of 14 cases who
      performed glycated hemoglobin test, one case from a family health center had
      value below 7%. The last measured systolic blood pressure was below 140 mm/Hg for
      64.6% of all patients while the last measured diastolic blood pressure was less
      than 90 mm/Hg for 58.1% of all patients. The total cholesterol level was equal or
      less than 193 mg/dl for 50.5% of tested 194 patients. Outcome measures showed
      better control of blood pressure and cholesterol level in patients attended
      family health units than patients attended family health centers. CONCLUSION AND
      RECOMMENDATIONS: Diabetes care provided by family health facilities in Al
      Montazah health district, Alexandria, was not conforming to diabetes practice
      guidelines for family physicians. Patient's co-payment might play a role in the
      low performance of expensive diabetes preventive services. It was recommended to
      adjust fee for diabetes preventive services according to patients' willingness to
      pay and to conduct further studies to investigate the effect of financing methods
      on the quality of care provided under the Egyptian Health Sector Reform Program.

PMID- 20673566
TI  - Measuring Patient Safety Culture in Riyadh's Hospitals: A Comparison between
      Public and Private Hospitals.
AB  - BACKGROUND: The issue of patient safety has received an increasing attention
      worldwide. In Saudi Arabia, policy makers and health organizations continually
      strive to substantially reduce medical errors and improve quality of health care.
      The aim of this research was to explore the perceptions of Riyadh hospitals'
      staff on patient safety and error reporting and to identify factors that
      influence the levels of frequency of events reported. MATERIAL AND METHODS: A
      cross-sectional survey, using Hospital Survey on Patient Safety Culture (HSPSC),
      was carried out in 2008. The questionnaire was distributed to all hospitals'
      staff in Riyadh, which included nine public hospitals and two private hospitals.
      A total of 1224 questionnaires were returned over a six-month period, giving a
      response rate of 47.4%. RESULTS: Organizational learning was the safety culture
      dimension with the highest positive response (75.9%), while the non-punitive
      response to error received the lowest positive response (21.1%). The key areas
      that need improvement in public hospitals include handoffs and transitions,
      communication openness, staffing, and non-punitive response to error. The private
      hospitals need an improvement in two aspects; staffing and non-punitive response
      to error. The results show that all types of mistakes were reported more
      frequency in private hospitals than in public hospitals. Most respondents
      reported "no events" in the twelve months preceding the survey, with the
      percentage of not reporting being higher in private sector compared to public
      hospitals. The high percent of "no event" reports may represent under-reporting
      in all hospitals. Regression analysis indicated that event reporting was
      influenced by feedback and communication about error, staff position, teamwork
      across units, non- punitive response to error, supervisor/managers expectations
      and actions promoting patients safety, and type of hospital. CONCLUSION AND
      RECOMMENDATIONS: Areas needs improvement in Riyadh hospitals includes handoffs
      and transitions, communication openness, staffing and non-punitive response to
      error. Healthcare organizations should reduce the fear of blame culture and
      create a climate of open communication and continuous learning.

PMID- 20673567
TI  - Miss and missed diagnosed cases at the emergency department of king fahd hospital
      of the university in khobar, king saudi arabia.
AB  - BACKGROUND: Medical errors in the emergency department (ED) are common, and
      proportion of preventable adverse events is among the highest for all areas of
      medical care. Some of the most common types of medical mistakes in ED include
      misdiagnosis, medication errors, surgery errors, nosocomial infections,
      laboratory test errors, and administrative errors. The present work aims to
      assess rate and identify contributing factors to miss and missed diagnoses at the
      ED of King Fahd Hospital of the University (KFHU) in Khobar, KSA. METHODS: It is
      a retrospective cohort study. Target population was medical records and database
      of inpatients admitted from the ED to the study hospital during the year 2007 and
      the study sample amounted to 441 cases. Accuracy of the diagnosis in the present
      study was assessed by comparing the degree of matching between ED diagnosis and
      the final discharge diagnosis using (ICD-9-CM) diagnostic codes. Accuracy of
      diagnosis was divided into four main categories: fully matched, partially
      matched, unmatched and symptoms& unspecific. However, missed diagnosis was
      defined as cases where the ED diagnosis was not documented in the ED sheet.
      RESULTS: Missed diagnosis represented (8.4%), fully/partially matched diagnosis
      was 62.3%, unmatched diagnosis was 10.7% and symptoms & unspecific diagnosis was
      (18.6%). Consultants experienced high percentage of fully/partially matched
      diagnosis (65.3%), while interns experienced high percentage of unmatched
      diagnosis (26.3%). The percentage of unmatched diagnosis at night shifts was
      relatively high 18.9%. Also, slightly more than one fifth of cases were diagnosed
      as symptoms & unspecific at evening shifts (21.2%). CONCLUSION AND
      RECOMMENDATIONS: Percentages of missed and unmatched diagnoses were relatively
      high. Also, percentage of unmatched diagnosis at night shifts and symptoms &
      unspecific diagnosis at evening shifts were high. The level of performance of
      interns was low in comparison to consultants leading to high percentage of
      unmatched diagnosis. Continuous medical education and training of ED physicians
      especially junior staff to continually improve their knowledge and skills,
      appropriate supervision of the medical staff to ensure competence, and proper
      manpower planning and recruitment to compensate for shortage of the ED medical
      staff especially at night shifts were highly recommended.

PMID- 20673568
TI  - Risk factors of oral health problems among adults in marion county, indiana, USA.
AB  - OBJECTIVE: This study aimed to identify the risk factors associated with
      orodontal diseases (ODD), including periodontal diseases (PDD) with or without
      dental caries (DC), in Marion County, Indianapolis, Indiana, USA. MATERIAL AND
      METHODS: A questionnaire was mailed to 121 randomly selected residents in Marion
      County. The number of visits to dentist in the two-year duration prior to the
      survey was studied, an indicator of the demand for orodontal care. RESULTS: The
      study provided that ODD was still recording as high as a 61.6% prevalence rate in
      Marion County. The number of dental visits significantly correlated with age,
      sex, race, and income (r =0.778, p<0.001). Also ODD significantly increased by
      age (p=0.011). Gender was not a risk factor for ODD (OR=0.885, 95% CI 0.412,
      1.902). CONCLUSIONS AND RECOMMENDATIONS: With such rates and in the presence of
      the available oral health programs, it is concluded that oral health problems
      pose a threat to the public health in Marion County's health resources. The
      rising demand for dental services depletes resources and exaggerates the
      likelihood of health disparity. An overall evaluation of the dental care system
      in Marion County, focusing on prevention is stressing.

PMID- 20673569
TI  - Role of action observation and action in sequence learning and coding.
AB  - A complex sequence learning task was used to determine if the type of coding
      acquired through physical practice (PP), observation of the stimulus (Obs-S), or
      observation of stimulus and action (Obs-SA) differs between conditions and
      whether the type of observation influences subsequent learning of the task when
      physical practice was permitted. Participants in the Obs-S group were permitted
      to watch the sequentially illuminated stimuli on the screen. In the Obs-SA group
      participants could see both flexion-extension movements of the model's arm
      performing the sequence and the sequentially illuminated stimuli on the screen.
      Participants in the PP group actually performed the 16-element sequence with
      their dominant right arm. Delayed retention tests and two inter-manual transfer
      tests were completed following each of two acquisition sessions. First, the data
      indicated that learning the sequence structure, as revealed by response time per
      element, occurred similarly irrespective of the initial practice condition.
      Secondly, the movement sequence appeared to be coded in abstract visual-spatial
      coordinates resulting in effector-independent performance. Finally, observing the
      model's action and sequential stimuli allows participants to transfer the
      perceived aspects of the movement sequence into efficient coordination patterns
      when additional physical practice is permitted.

PMID- 20673570
TI  - Decontamination of textile wastewater via TiO2/activated carbon composite
      materials.
AB  - Water scarcity and pollution rank equal to climate change as the most urgent
      environmental turmoil for the 21st century. To date, the percolation of textile
      effluents into the waterways and aquifer systems, remain an intricate conundrum
      abroad the nations. With the renaissance of activated carbon, there has been a
      steadily growing interest in the research field. Recently, the adoption of
      titanium dioxide, a prestigious advanced photo-catalyst which formulates the new
      growing branch of activated carbon composites for enhancement of adsorption rate
      and discoloration capacity, has attracted stern consideration and supports
      worldwide. Confirming the assertion, this paper presents a state of art review of
      titanium dioxide/activated carbon composites technology, its fundamental
      background studies, and environmental implications. Moreover, its major
      challenges together with the future expectation are summarized and discussed.
      Conclusively, the expanding of activated carbons composites material represents a
      potentially viable and powerful tool, leading to the plausible improvement of
      environmental conservation.

PMID- 20673571
TI  - The role of experience in night work: Lessons from two ergonomic studies.
AB  - The purpose of this article is to analyze some connections between experience,
      health and work, especially in the field of night work. As a result of the baby
      boom, the proportion of elderly workers is steadily increasing, while at the same
      time many workers are reaching retirement age and being replaced by younger
      people. And, in the same time, there is an overall gradual increase in shift work
      and night work. To our knowledge, worker experience has not been extensively
      studied in this context. This was our focus in studying work activity in two very
      different situations, in a hospital and in a steel industry. In these two studies
      we observed that the experienced workers endeavor to plan ahead, especially at
      night. They do this to limit fatigue and to avoid emergencies and ensure that
      work is stress-free and as far as possible under control. But experience not only
      brings workers to plan ahead, it also enables them to do so, thanks to the
      resources it confers: gaining familiarity with tasks and acquiring the ability to
      identify critical situations, gaining knowledge about themselves and awareness of
      situations that cause difficulty; and gaining a better overview of the collective
      aspects of their work and of ways to share tasks or obtain assistance. They are
      able to undertake these strategies thanks to specific skills and capacities they
      have built along their professional career, which notably leads them to find the
      best trade-off between several goals, possibly contradictory. Such experience is
      especially valuable at night, when the worker is tired, and when there are fewer
      supervisors present. This experience can only be gained, however, if the work
      environment fosters its acquisition and provides an opportunity to make use of
      it, especially during the night shift and especially with respect to planning
      tasks ahead of time.

PMID- 20673572
TI  - Long-haul pilots use in-flight napping as a countermeasure to fatigue.
AB  - The aim of this study was to examine the effects of fatigue on the amount of in
      flight sleep obtained by airline pilots during long-haul duty periods. A total of
      301 pilots collected sleep/wake and work/rest data for a period of at least 2
      weeks each. Fatigue likelihood, i.e. low, moderate, high, or extreme, was
      estimated for each duty period based on a pilot's sleep/wake behaviour prior to
      duty and the time of day that the duty period occurred. Participants obtained 1.8
      h of sleep (i.e. 27% of their rest time) during duty periods with low fatigue
      likelihood and 3.7 h of sleep (i.e. 54% of their rest time) during duty periods
      with extreme fatigue likelihood. These results indicate that (i) long-haul pilots
      obtain substantially more sleep during duty periods when fatigue is likely to be
      extreme than when fatigue is likely to be low and (ii) long-haul pilots use in
      flight napping as a fatigue countermeasure, but more could be done to increase
      its efficacy.

PMID- 20673573
TI  - When hoarding is a symptom of OCD: a case series and implications for DSM-V.
AB  - Hoarding, the excessive collection and failure to discard objects of apparently
      little value, can represent a serious psychiatric problem and pose a threat to
      public health. Hoarding has traditionally been considered a symptom (or symptom
      dimension) of Obsessive-Compulsive Disorder (OCD), but its nosological status has
      recently been debated. Mounting evidence suggests that, once other primary causes
      are ruled out, hoarding may be a discrete diagnostic entity, recently named
      Hoarding Disorder. However, hoarding can sometimes be a genuine OCD symptom. This
      can be confusing and clinicians may sometimes struggle making the differential
      diagnosis. To illustrate this, we describe 10 OCD patients with severe hoarding
      behavior that is better conceptualized as a symptom of OCD. We focus on the
      motivations for hoarding and the overlapping of hoarding with other obsessive
      compulsive symptom dimensions. We estimate that this clinical presentation is
      relatively rare and accounts for a minority of severe hoarding cases. We discuss
      the unique characteristics of hoarding as a symptom of OCD and the implications
      for DSM-V.

PMID- 20673574
TI  - Phosphorylated glucosamine inhibits the inflammatory response in LPS-stimulated
      PMA-differentiated THP-1 cells.
AB  - This study evaluated the effect of phosphorylated glucosamine (pGlc) on the
      regulation of cytokines involved in immunological activities. Changes in the
      inflammatory profiles of lipopolysaccharide (LPS)-stimulated phrobol 12-myristate
      13-acetate (PMA)-differentiated THP-1 macrophage models were investigated
      following pGlc treatment. Treatment with pGlc inhibited the production of pro
      inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha),
      interleukin-1beta (IL-1beta), and interleukin-6 (IL-6). In addition, pGlc
      suppressed the regulation of inflammatory mediators such as TNF-alpha, IL-1beta,
      IL-6, inducible NO synthase (iNOS), and cyclooxygenase-2 (COX-2) in LPS
      stimulated THP-1 macrophages. Furthermore, we confirmed that the LPS-stimulated
      transcription of MAP kinases in PMA-differentiated THP-1 macrophages was
      inhibited by pGlc. According to this study, pGlc can be considered as a potential
      anti-inflammatory agent.

PMID- 20673575
TI  - Isolation and structure elucidation of 5'-O-beta-D-glucopyranosyl
      dihydroascorbigen from Cardamine diphylla rhizome.
AB  - From the methanol extract of Cardamine diphylla rhizome, 5'-O-beta-d
      glucopyranosyl-dihydroascorbigen (1) and 6-hydroxyindole-3-carboxylic acid 6-O
      beta-d-glucopyranoside (2) were isolated. The structures of the compounds were
      elucidated using spectroscopic methods. This is the second report on the presence
      of a glucosylated indole ascorbigen in plants.

PMID- 20673576
TI  - What is the financial cost of treating periprosthetic hip fractures?
AB  - A total of 146 patients were identified from a prospective database of all hip
      fractures over a 10-year period at a United Kingdom teaching hospital. The
      financial costs were calculated and analysed and then compared with the money
      recovered through the tariff produced by Payment by Results.A total of 62% of the
      study group were female; mean age of 79 years; mean length of stay of 39
      days.Fractures occurred around total hip replacement (THR) in 63 cases, revision
      THR in 27 cases and hemiarthroplasty in 56 cases. Fixation of the fracture was
      performed in 61 cases, revision arthroplasty in 62 cases and 23 were treated non
      operatively.The mean cost of treatment was L23,469 per patient (range L615
      L223,000; median L18,031). Ward costs were responsible for 80.3%, theatre costs
      5.7%, implants 6.7% and investigations 7.3%. The difference in cost was
      statistically significant when further surgery was required (p = 0.01) and length
      of stay was greater than 30 days (p < 0.0001), and when compared with the money
      recovered by the Trust(mean L3702; p < 0.0001). These results reveal the
      significant economic impact of treating this group of patients at specialist
      centres.

PMID- 20673577
TI  - Membrane stretch and cytoplasmic Ca2+ independently modulate stretch-activated BK
      channel activity.
AB  - Large conductance Ca(2+)-activated K(+) (BK) channels are responsible for changes
      in chemical and physical signals such as Ca(2+), Mg(2+) and membrane potentials.
      Previously, we reported that a BK channel cloned from chick heart (SAKCaC) is
      activated by membrane stretch. Molecular cloning and subsequent functional
      characterization of SAKCaC have shown that both the membrane stretch and
      intracellular Ca(2+) signal allosterically regulate the channel activity via the
      linker of the gating ring complex. Here we investigate how these two gating
      principles interact with each other. We found that stretch force activated SAKCaC
      in the absence of cytoplasmic Ca(2+). Lack of Ca(2+) bowl (a calcium binding
      motif) in SAKCaC diminished the Ca(2+)-dependent activation, but the
      mechanosensitivity of channel was intact. We also found that the abrogation of
      STREX (a proposed mechanosensing apparatus) in SAKCaC abolished the
      mechanosensitivity without altering the Ca(2+) sensitivity of channels. These
      observations indicate that membrane stretch and intracellular Ca(2+) could
      independently modulate SAKCaC activity.

PMID- 20673578
TI  - Highly sensitive determination of recombinant human erythropoietin-alpha in
      aptamer-based affinity probe capillary electrophoresis with laser-induced
      fluorescence detection.
AB  - Recombinant human erythropoietin-alpha (rHuEPO-alpha) has been widely used in
      clinic for anemia treatment. The detection and quantification of rHuEPO-alpha is
      essential for monitoring this widespread recombinant glycoprotein pharmaceutical.
      In this paper, we developed a new affinity probe capillary electrophoresis/laser
      induced fluorescence (APCE/LIF) method for the detection of rHuEPO-alpha by using
      a specific single-stranded DNA aptamer probe for the first time. In this method,
      the complex of aptamer-rHuEPO-alpha and the free aptamer can be well separated
      and identified by their migration and fluorescence intensity after systematic
      optimization. The existence of sodium cation in the sample buffer and running
      buffer played a critical role for stabilizing complex and enhancing the
      separation efficiency, additionally, suitable high voltage and sample buffer
      additives were also important for improving the peak height of the complex. Under
      the optimized conditions, the method was successfully applied for the
      quantification of rHuEPO-alpha in physiological buffer, artificial urine and
      human serum. The linear range for rHuEPO-alpha was from 0.2 to 100 nM and the
      limit of detection was 0.2 nM (i.e. 7.4 ng/mL). Further binding experiments using
      fluorescein isothiocyanate-labeled rHuEPO-alpha (F-rHuEPO-alpha) and N
      deglycosylated F-rHuEPO-alpha demonstrated that the oligosaccharides moiety was
      of importance in the specific interaction between rHuEPO-alpha and its aptamer.

PMID- 20673579
TI  - Holistic versus analytic processing: evidence for a different approach to
      processing of Chinese at the word and character levels in Chinese children.
AB  - Among 30 Hong Kong Chinese fourth graders, sensitivities to character and word
      constructions were examined in judgment tasks at each level. There were three
      conditions across both tasks: the real condition, consisting of either actual two
      character compound Chinese words or real Chinese compound characters; the
      reversed condition, with either the order of the two morphemes in the word or the
      order of the semantic and phonetic radicals in the character reversed; and the
      random condition, with either two morphemes randomly combined to create arbitrary
      nonwords or a semantic radical and a phonetic radical randomly combined using
      correct orthographic rules to create noncharacters. On the word level, children
      performed worst in the reversed condition and best with real words, whereas on
      the character level, children performed worst in the random condition and best in
      the reversed condition. Findings imply a holistic tendency toward word-level
      processing and an analytic approach to character-level processing in these
      Chinese children.

PMID- 20673580
TI  - Individual differences in growth in executive function across the transition to
      school predict externalizing and internalizing behaviors and self-perceived
      academic success at 6 years of age.
AB  - Building on an existing latent variable analysis of executive function (EF) in
      children (N=191, 57% boys and 43% girls) making the transition to school (Hughes
      et al. (2010), Developmental Neuropsychology, vol. 35, pp. 20-36), the current
      study both documented average developmental improvements from 4 to 6years of age
      and examined individual differences in EF growth in relation to latent factors
      for two sets of child outcome measures at 6years: (a) first-grade teachers'
      ratings of emotional symptoms, hyperactivity, and conduct/peer problems and (b)
      children's self-perceived academic and social competencies. With effects of
      concurrent verbal ability and EF controlled, variation in EF slopes across the
      transition to school predicted variation in latent constructs for (a) all four
      problem behavior subscales and (b) children's self-reported academic (but not
      social) competence. These findings underscore the clinical and educational
      significance of early individual differences in EF and highlight the value of
      adopting a developmental perspective.

PMID- 20673581
TI  - [Treatment of hepatocellular carcinoma using precision transcatheter arterial
      chemoembolization (TACE): results of two years' experience in a general
      hospital].
AB  - OBJECTIVES: To present our experience in the use of microspheres preloaded with
      adriamycin (DC Bead((r))) in the transcatheter arterial chemoembolization (TACE)
      of hepatocellular carcinoma, in a two-year prospective multidisciplinary study in
      consecutive patients to evaluate the efficacy, safety, and tolerance of this
      procedure. MATERIAL AND METHODS: From May 2007 to January 2010, we performed 30
      TACE procedures in 17 patients (3 women and 14 men; mean age, 68 years; age
      range, 56-85 years). We performed a mean of 1.76 procedures per patient using the
      precision TACE protocol. Outcomes were evaluated using the RECIST-EASL criteria
      by clinical, laboratory, CT, and MRI follow-up at 1, 3, 6, and 12 months.
      RESULTS: The procedure was considered an initial technical success in all cases.
      The total dose was delivered in seven cases; in the remaining cases, the total
      dose was not reached (mean dose, 80mg). An objective response was observed in
      64.7% of patients: a complete response was observed in 29.41% and a partial
      response in 35.29%. Disease was stabilized in 23.52% and progressed in 11.76%. We
      observed two cases of abscess/necrosis and one of ischemic cholecystitis. There
      were no deaths or cases of liver failure related with the procedure. CONCLUSIONS:
      TACE using microspheres preloaded with adriamycin (DC Beads(r)) is safe and
      effective, given the low rate of complications, good tolerance in patients, and
      increased tumor response.

PMID- 20673582
TI  - Interspecies correlations of toxicity to eight aquatic organisms: theoretical
      considerations.
AB  - Interspecies correlations allow the prediction of toxicity to a number of other
      species. However, little attention has been paid to the theoretical
      considerations of the interspecies relationship based on the differences of bio
      uptake and toxic mechanism between species. This study examines the interspecies
      correlations of toxicity between species of Vibrio fischeri, river bacteria,
      algae, Daphnia magna, carp, Tetrahymena pyriformis, fathead minnow and guppy
      based on the theoretical background. The results show that there are good
      interspecies correlations between marine bacterium and fresh water bacteria or
      fish and fish. It is suggested that compounds share the same bio-uptake and toxic
      mechanism of action between the species. On the other hand, poor interspecies
      relationships were found between toxicities to algae and T. pyriformis or D.
      magna. It is suggested that compounds have different toxic mechanisms of action
      between these species. Interspecies relationships can be improved by inclusion of
      the octanol/water partition coefficient or the energy of the lowest unoccupied
      molecular orbital. They reflect the difference of bio-uptake or toxic mechanism
      of action between species for organic compounds. Benzoic acids show very
      different toxicity contributions to the three species, V. fischeri, D. magna and
      carp. They can be easily absorbed into the unicellular bacteria, V. fischeri. On
      the contrary, the skin and lipid content of multicellular organisms, such as D.
      magna and fish, can strongly inhibit the bio-uptake for ionizable compounds,
      which results in the different toxic effect between V. fischeri and D. magna or
      carp. Good correlation coefficients were observed between toxicities to V.
      fischeri and D. magna or fishes by inclusion of hydrophobic and ionization
      parameters. V. fischeri or D. magna can serve as a surrogate of fish toxicity for
      hydrophobic and ionizable compounds studied. Toxic mechanisms of action are
      discussed based on the theoretical background of the interspecies correlation.

PMID- 20673583
TI  - Gestational trophoblastic disease.
AB  - Gestational trophoblastic disease encompasses a range of pregnancy-related
      disorders, consisting of the premalignant disorders of complete and partial
      hydatidiform mole, and the malignant disorders of invasive mole, choriocarcinoma,
      and the rare placental-site trophoblastic tumour. These malignant forms are
      termed gestational trophoblastic tumours or neoplasia. Improvements in management
      and follow-up protocols mean that overall cure rates can exceed 98% with
      fertility retention, whereas most women would have died from malignant disease 60
      years ago. This success can be explained by the development of effective
      treatments, the use of human chorionic gonadotropin as a biomarker, and
      centralisation of care. We summarise strategies for management of gestational
      trophoblastic disease and address some of the controversies and future research
      directions.

PMID- 20673584
TI  - The role of biosilica in the osteoprotegerin/RANKL ratio in human osteoblast-like
      cells.
AB  - Earlier studies have demonstrated that biosilica, synthesized by the enzyme
      silicatein, induces hydroxyapatite formation in osteoblast-like SaOS-2 cells.
      Here we study the effect of biosilica on the expressions of osteoprotegerin [OPG]
      and the receptor activator for NF-kappaB ligand [RANKL] in the SaOS-2 cell model.
      We show that during growth of SaOS-2 cells on biosiliceous matrices
      hydroxyapatite formation is induced, while syntheses of cartilaginous
      proteoglycans and sulfated glycosaminoglycans are down-regulated. Furthermore,
      quantitative real-time RT-PCR analysis revealed a strong time-depended increase
      in expression of OPG in biosilica exposed SaOS-2 cells while the steady-state
      expression level of RANKL remained unchanged. These results have been
      corroborated on the protein level by ELISA assays. Therefore, we propose that
      biosilica stimulated OPG synthesis in osteoblast-like cells counteracts those
      pathways that control RANKL expression and function (e.g. maturation of pre
      osteoclasts and activation of osteoclasts). Hence, the data obtained in the
      present study reveal the considerable biomedical potential of biosilica for
      treatment and prophylaxis of osteoporotic disorders.

PMID- 20673585
TI  - Short and long term effects of granulocyte colony-stimulating factor during
      induction therapy in acute myeloid leukemia patients younger than 65: results of
      a randomized multicenter phase III trial.
AB  - This prospective multicenter phase III clinical trial was designed to assess
      efficacy and safety of G-CSF as an adjunct to de novo AML remission induction
      therapy (www.clinicaltrials.gov. NCT00820976). Patients' characteristics were
      similar in both arms. G-CSF improved severity and duration of leukopenia. Three
      year OS were similar (25.6 +/- 5.1% vs. 31.8 +/- 5.6%) in both arms except for
      patients with myeloblastic features. Significant factors for better survival were
      the use of G-CSF (p=0.049), female sex (p=0.05) and single induction cycle
      (p<0.001) in multivariate analysis. Female patients performed better than male
      patients. Better survival obtained among female AML patients needs to be
      validated within the context of cytogenetic analysis.

PMID- 20673586
TI  - Longitudinal studies of SRC family kinases in imatinib- and dasatinib-resistant
      chronic myelogenous leukemia patients.
AB  - This report aims to more accurately define the frequency of the involvement of
      SRC Family Kinases (SFKs) in imatinib- and dasatinib-resistant CML patients.
      Clinical samples were analysed during in vivo treatment. We confirmed the high
      frequency of SFKs involvement in Tyrosine kinase inhibitor-resistant CML (52% of
      the cases) and even further in progressive disease and blast crises (60% of the
      cases). The SFKs deregulation is also observed in patients harboring BCR-ABL
      mutations. In T315I and F317L mutated patients, CML-resistance appears to be
      promoted by SFKs kinase protein reactivation once the BCR-ABL mutated clone has
      decreased on Omacetaxine.

PMID- 20673587
TI  - Do subtypes of graves' orbitopathy exist?
AB  - PURPOSE: To describe the prevalence of fat and muscle volume (MV) increase in
      Graves' orbitopathy (GO) patients, calculated from computed tomography scans, and
      the associated ophthalmic and endocrine characteristics. DESIGN: Consecutive,
      observational case series. PARTICIPANTS: Ninety-five consecutive Caucasian GO
      patients attending the thyroid eye clinic. METHODS: Volumetry using age-specific
      reference values in untreated GO patients who had been rendered euthyroid. MAIN
      OUTCOME MEASURES: Subgroups in GO and main characteristics. RESULTS: Four
      subgroups could be distinguished: Group 1, no fat volume (FV) or MV increase (n =
      24); group 2, only FV increase (n = 5); group 3, only MV increase (n = 58); and
      group 4, both FV and MV increase (n = 8). Patients with an increase of MV were
      older and had higher thyroid-stimulating hormone-binding inhibitory
      immunoglobulin TBII, more proptosis, and more impaired ductions than those
      without MV increase. Patients with an increase of FV differed from those without
      FV increase only in having more proptosis. The clinical activity score did not
      differ between the 4 groups. CONCLUSIONS: Of these GO patients, 25% have orbital
      fat and MVs within an age-specific reference range. An increase of the FV is seen
      in only 14% of GO patients and characterized by proptosis. Muscle enlargement
      occurs in 70% of patients and is associated with older age, higher TBII values,
      more proptosis, and impaired motility.

PMID- 20673588
TI  - Long-term phenotypic study after allogeneic cultivated corneal limbal epithelial
      transplantation for severe ocular surface diseases.
AB  - PURPOSE: To determine the long-term epithelial lineage of origin of surgically
      removed grafts after allogeneic cultivated corneal limbal epithelial
      transplantation (CLET). DESIGN: Interventional case reports. PARTICIPANTS: We
      studied 2 eyes from 2 patients with total corneal stem cell destruction; 1 eye
      was from a patient with Stevens-Johnson syndrome and 1 eye had sustained chemical
      injury. METHODS: Allogeneic cultivated corneal limbal epithelial sheets on human
      amniotic membrane (AM) were transplanted onto the ocular surface. Regrafting (1
      eye, 42 months later) or penetrating keratoplasty (1 eye, 75 months later) were
      performed after the initial transplantation procedure for further visual
      rehabilitation. MAIN OUTCOME MEASURES: The excised grafts were subjected to
      clinical evaluation and to light- and transmission electron microscopy (TEM)
      examination and to immunohistochemical analysis. RESULTS: In clinically
      conjunctival grafts, TEM and immunohistochemical analysis disclosed only small
      areas where the original cultivated corneal epithelial cells persisted.
      Neighboring conjunctival epithelial cells had apparently invaded a large portion
      of the corneal surface (keratin 3/12(-), Muc5ac(+)). In clinically corneal
      grafts, transplanted allogeneic cultivated corneal epithelial cells clearly
      survived for a long period of time (keratin 3/12(+), Muc5ac(-)); there was no
      infiltration by inflammatory cells, nor was there dissolution of the AM
      substrate. CONCLUSIONS: We theorize that the process of graft opacification after
      allogeneic CLET is responsible for the loss of transplanted cultivated corneal
      epithelial cells and that this is followed by conjunctival cell invasion onto the
      corneal surface. The results of this study confirmed that in the clinically
      evaluated corneal graft, transplanted cultivated corneal epithelial cells indeed
      survived for a long period of time on the corneal surface and maintained ocular
      surface integrity, even though the transplanted cells were allogeneic.

PMID- 20673589
TI  - Effects and complications of bevacizumab use in patients with retinopathy of
      prematurity: a multicenter study in taiwan.
AB  - PURPOSE: To investigate the effects and complications of the anti-vascular
      endothelial growth factor agent bevacizumab in the treatment of retinopathy of
      prematurity (ROP) in Taiwanese patients. DESIGN: A multicenter, retrospective
      case series study. PARTICIPANTS: Twenty-seven patients (49 eyes) from 4 medical
      centers across Taiwan. METHODS: This study included patients receiving
      intravitreal injections of bevacizumab (IVB) (0.625 mg) for the treatment of ROP
      between 2007 and 2009 at 4 major medical centers in Taiwan. The effects and
      complications associated with this treatment were analyzed. Patients were
      followed for at least 6 months after bevacizumab injection. MAIN OUTCOME
      MEASURES: Regression of ROP and the complications associated with the injection
      of bevacizumab. RESULTS: Forty-nine eyes of 27 patients (18 male and 9 female)
      were included in the study. Mean gestational age and birth weight were 26.0 +/-
      2.4 weeks and 971.6 +/- 589.6 g, respectively. There were 41 eyes (23 patients)
      with stage 3 ROP, 6 eyes (3 patients) with stage 4A ROP, and 2 eyes (1 patient)
      with stage 5 ROP. All of the eyes received only a single injection of IVB. The
      mean injection time was 36.8 +/- 2.6 weeks postmenstrual age for eyes with stage
      3 ROP. A total of 37 of 41 eyes (90%) with stage 3 ROP regressed after
      bevacizumab injection only. Four eyes (10%) required additional laser treatment
      to regress the ROP. Of 6 eyes (3 patients) with stage 4A ROP, 2 eyes (1 patient;
      33%) regressed after bevacizumab injection and 4 eyes (67%) regressed after
      bevacizumab injection and subsequent vitrectomy. The 2 eyes with stage 5 ROP
      exhibited decreased vascular tortuosity after bevacizumab injection, but the
      retina failed to reattach after vitrectomy surgeries. Major complications
      included vitreous or pre-retinal hemorrhage in 4 eyes (8%) and transient vascular
      sheathing in 2 eyes (4%). CONCLUSIONS: Bevacizumab injection seems effective and
      well tolerated in some cases of ROP, especially in stage 3 ROP. Ocular
      complications could result from the injection of bevacizumab in pediatric eyes.

PMID- 20673590
TI  - High-resolution imaging of resolved central serous chorioretinopathy using
      adaptive optics scanning laser ophthalmoscopy.
AB  - OBJECTIVE: To compare pathologic changes in photoreceptors in eyes with resolved
      central serous chorioretinopathy (CSC) seen on high-resolution images obtained by
      adaptive optics scanning laser ophthalmoscopy (AO SLO) with visual acuity (VA)
      and findings on spectral-domain optical coherence tomography (SD OCT). DESIGN:
      Observational case series. PARTICIPANTS: Forty-five eyes of 38 patients with
      resolved CSC and 20 normal eyes of 20 volunteer subjects. METHODS: All patients
      underwent a full ophthalmologic examination, SD OCT, and imaging with an original
      prototype AO SLO system fabricated using liquid crystal-on-silicon technology.
      MAIN OUTCOME MEASURES: Cone mosaic patterns and cone density on AO SLO images and
      VA in eyes with CSC. RESULTS: In normal eyes, AO SLO images showed a regular
      photoreceptor mosaic pattern and average cone densities 0.2, 0.5, and 1.0 mm from
      the central fovea of 67,900, 33,320, and 14,450 cones/mm(2). In eyes with CSC,
      cone densities were significantly lower at each distance from the central fovea
      (P = 0.009 at 0.2 mm, P = 0.007 at 0.5 mm, and P = 0.004 at 1.0 mm), and 2
      distinct cone mosaic patterns were seen. Group 1 CSC eyes had regular cone mosaic
      patterns with small dark regions. Group 2 CSC eyes had irregular mosaic patterns
      with large dark regions. Compared with group 1, group 2 had significantly lower
      average cone density and worse average logarithm of the minimum angle of
      resolution (logMAR) VA (P<0.001). Mean cone density in eyes with disruptions in
      the photoreceptor inner and outer segment (IS/OS) junction or in the intermediate
      line on SD OCT images was significantly lower than that in eyes with an intact
      IS/OS junction or intermediate line (P<0.001 for both). Cone density 0.2 mm from
      the central fovea correlated with logMAR VA and mean foveal thickness (1-mm
      diameter area) measured on SD OCT images (P<0.001 for both). CONCLUSIONS:
      Adaptive optics SLO images showed abnormal cone mosaic patterns and reduced cone
      densities in eyes with resolved CSC, and these abnormalities were associated with
      VA loss, suggesting that AO SLO is a useful means to detect and measure cone
      abnormalities associated with VA loss in these eyes.

PMID- 20673592
TI  - Cytotoxicity effects of water dispersible oxidized multiwalled carbon nanotubes
      on marine alga, Dunaliella tertiolecta.
AB  - The multiwalled carbon nanotubes (MWNTs) are novel materials with many potential
      applications. The ecotoxicity of these materials is not well studied, but it is
      essential for environmental impact assessments. In this study a commercially
      available MWNT material was carboxylated by microwave assisted acid oxidation.
      This functionalized MWNT (f-MWNT) material was examined for toxicity effects
      using unicellular marine green alga Dunaliella tertiolecta. D. tertiolecta was
      exposed to f-MWNT which had been pre-equilibrated with culture media for 24 h.
      Substantial growth lag phase was observed at 5 and 10 mgL(-1) f-MWNT, and the
      resulting 50% effective concentration (EC50) on 96-h growth was 0.82 +/- 0.08
      mgL(-1). During mid-exponential growth phase cytotoxicity was evidenced at 10
      mgL(-1) f-MWNT in 36% reduction in exponential growth rate, 88 mV more positive
      glutathione redox potential (indicative of oxidative stress), 5% and 22%
      reduction in photosystem II (PSII) quantum yield and functional cross section
      respectively, all relative to the control cultures. However, when the large f
      MWNT aggregates in the media with 10 mgL(-1) f-MWNT were removed by 0.2 MUm
      filtration, D. tertiolecta did not show significant cytotoxicity effects in any
      of the above parameters. This suggests that the cytotoxicity effects originated
      predominantly from the large f-MWNT aggregates. Analysis of the f-MWNT
      aggregation dynamics suggests active interaction between f-MWNT and algal cells
      or cell metabolites that promoted f-MWNT aggregation formation. The f-MWNT
      particles were also found absorbed on algal cell surface. The direct contact
      between f-MWNT and cell surface was likely responsible for reduced PSII
      functional cross section and oxidative stress during exponential growth.

PMID- 20673593
TI  - Impact of water activity of diverse media on spore germination of Aspergillus and
      Penicillium species.
AB  - The effects of water activity (a(w)) of diverse media i/ culture medium for
      sporogenesis, a(w sp) ii/ liquid spore suspension medium, a(w su) and iii/ medium
      for germination, a(w ge), on the germination time t(G) of Aspergillus
      carbonarius, Aspergillus flavus, Penicillium chrysogenum and Penicillium expansum
      were assessed according to a screening matrix at 0.95 and 0.99 a(w). It was shown
      that i/ reduced t(G)s were obtained at 0.95 a(w sp) except for P. expansum ii/ a
      significant effect of a(w su) on t(G) was demonstrated for A. carbonarius, P.
      chrysogenum and P. expansum iii/ the most important factor for controlling the
      germination time was the medium for germination except for A. carbonarius (a(w
      su)). In accordance with the fact that fungal spores can swell as soon as they
      are suspended in an aqueous solution it is recommended to re-suspend fungal
      spores in a solution at the same water activity as that of subsequent germination
      studies.

PMID- 20673594
TI  - Depression and hemoglobin A1c in type 1 and type 2 diabetes: the role of self
      efficacy.
AB  - AIMS: To examine a self-efficacy explanation of the finding that depression is
      related to hemoglobin A1c (A1c) level in people with type 1 but not type 2
      diabetes. METHODS: Cross-sectional design involving 124 participants with type 1
      (n=32) and type 2 (n=92) diabetes. Participants completed measures of depression
      and diabetes-related self-efficacy. A1c was obtained from medical records.
      RESULTS: Replicating prior findings, A1c was significantly correlated with
      depression in type 1 participants (r=.51, p<.01), but not in type 2 participants
      (r=.11, ns). As hypothesized, A1c was significantly correlated with self-efficacy
      among type 1 participants (r=-.42, p<.05) but not among type 2 participants (r=
      .01, ns). Self-efficacy also mediated the effect of A1c on depression among the
      type 1 participants (Z=2.21, p<.05). CONCLUSION: In people with type 1, but not
      type 2 diabetes, A1c levels are related to diabetes adherence mastery (self
      efficacy), which mediates the link between A1c and depression. Results are
      discussed with regard to the proposal that perceptions of ineffective control
      over one's health play a role in the development of depression (a consequence
      model of depression in diabetes).

PMID- 20673595
TI  - Hepatitis C virus infection: a "liaison a trois" amongst the virus, the host, and
      chronic low-level inflammation for human survival.
AB  - This review covers the various aspects of the immune system that allows the
      relationship between the hepatitis-C virus, the host and chronic low-level
      inflammation, to be highly flexible and able to defend the host from persistent
      infections. This ambiguity mainly stems from the property of the immune system
      that can be both protective and harmful. Immunity cannot be fully protective
      without producing a certain degree of damage (acute hepatitis resulting in
      resolving HCV infection). In addition, the balance between protection and tissue
      damage is critical for the development of chronic HCV infection. The
      establishment of a state of chronic low-level inflammation is instrumental to
      limit liver immunopathology, to limit viral spread, and ultimately to ensure a
      long-lasting survival of the host. It is dictated by a fine equilibrium
      maintained by multiple immunologic mechanisms, including: sensory perception of
      innate immunity, virus-specific T and B cell functions, control of immune
      responses, and finally the balance between immunity and immunopathology that has
      principally evolved to favor the survival of the species.

PMID- 20673596
TI  - Biomedical system based on the Discrete Hidden Markov Model using the Rocchio
      Genetic approach for the classification of internal carotid artery Doppler
      signals.
AB  - When the maximum likelihood approach (ML) is used during the calculation of the
      Discrete Hidden Markov Model (DHMM) parameters, DHMM parameters of the each class
      are only calculated using the training samples (positive training samples) of the
      same class. The training samples (negative training samples) not belonging to
      that class are not used in the calculation of DHMM model parameters. With the aim
      of supplying that deficiency, by involving the training samples of all classes in
      calculating processes, a Rocchio algorithm based approach is suggested. During
      the calculation period, in order to determine the most appropriate values of
      parameters for adjusting the relative effect of the positive and negative
      training samples, a Genetic algorithm is used as an optimization technique. The
      purposed method is used to classify the internal carotid artery Doppler signals
      recorded from 136 patients as well as of 55 healthy people. Our proposed method
      reached 97.38% classification accuracy with fivefold cross-validation (CV)
      technique. The classification results showed that the proposed method was
      effective for the classification of internal carotid artery Doppler signals.

PMID- 20673597
TI  - Comments on "Analytical modelling of fringe and core biodegradation in
      groundwater plumes." by Gutierrez-Neri et al. in J. Contam. Hydrol. 107: 1-9.
AB  - In this comment, we revisit equations concerning the analytical solutions
      presented by Gutierrez-Neri and co-workers for reactive transport for a pollutant
      undergoing core and fringe degradations. We state that a correction needs to be
      made in Eq. (9) of the work of Gutierrez-Neri et al. in order that the equation
      follows closely previous work published by J. Bear (in 1-D) and P.A. Domenico (in
      3-D). Furthermore we derive alternative solutions for Eqs. (13)-(16) which
      separate more clearly the first-order reaction and the instantaneous reaction. It
      is shown that the corrected solution agrees better with the results from the
      numerical model than the previous solution. An improvement is also made by giving
      a solution which avoids negative concentrations. Furthermore, the corresponding
      solution for the electron acceptor reacting with the pollutant is given.

PMID- 20673598
TI  - Outcomes and management costs in patients hospitalized for skin and skin
      structure infections.
AB  - BACKGROUND: This study was conducted to determine outcomes and costs of treating
      complicated skin and skin-structure infections (cSSSIs) due to gram-positive
      only, gram-negative only, or mixed pathogens (gram-positive and gram-negative),
      including those with methicillin-resistant Staphylococcus aureus (MRSA) or
      Pseudomonas aeruginosa. METHODS: Data on length of stay (LOS), mortality, and
      charges for cSSSIs were compiled from claims in the multihospital Solucient
      database from 2002 to 2006. RESULTS: Among the 5156 cases with pathogens
      identified, 59.7% were gram-positive, 21.5% were gram-negative, and 18.8% were
      mixed. Patients with mixed pathogens incurred significantly higher LOS (17.2
      days), mortality (10.2%), and charges ($80,093) than those with cSSSIs due to
      gram-negative pathogens (10.1 days, 6.5%, and $41,634, respectively) or to gram
      positive pathogens (9.5 days, 4.8%, and $40,046, respectively). MRSA was isolated
      from 21.6% of all cases and from 26.3% of cases involving mixed pathogens. MRSA
      cases had significantly longer LOS and greater mortality than non-MRSA cases, but
      similar total charges. P aeruginosa occurred in 13.3% of all cases and in 36.3%
      of cases involving mixed pathogens. P aeruginosa cases had significantly higher
      LOS and charges compared with non-P aeruginosa cases. CONCLUSION: Although gram
      positive pathogens were the most common causes of cSSSIs, cases involving mixed
      and resistant pathogens were associated with longer LOS, greater mortality, and
      higher total charges.

PMID- 20673599
TI  - A field trial evaluating the Quantiferon Gold tuberculosis tube test in an
      endemic population.
AB  - The Quantiferon Gold tuberculosis tube test is a sensitive and specific way to
      diagnosis latent and active tuberculosis. The test is easy to administer and
      potentially can be used under field conditions and in a remote analytical
      laboratory. We screened an endemic population under field conditions and
      transferred our specimens via express mail to a distant site for analysis.

PMID- 20673600
TI  - Fathers in the birth room: what are they expecting and experiencing? A
      phenomenological study.
AB  - OBJECTIVE: to explore the role, expectations and meanings that individual fathers
      ascribe to their presence at birth. DESIGN: a Heideggerian phenomenological
      approach utilising in-depth interviews at two different time points. SETTING:
      large tertiary maternity unit in the North West of England. PARTICIPANTS: 11
      first-time fathers accessed through hospital-based parentcraft sessions.
      FINDINGS: four main themes were evident: fathers' disconnection with pregnancy
      and labour; fathers on the periphery of events during labour; control; and
      fatherhood beginning at birth and reconnection. KEY CONCLUSIONS: birth is the
      moment that fathers ascribe as the beginning of fatherhood. However, through
      their lack of knowledge and perceived control, they struggle to find a role
      there. IMPLICATIONS FOR PRACTICE: midwives are ideally placed to help fathers to
      find a role through parentcraft and encouraging participation at birth.

PMID- 20673601
TI  - Effect of daily hemodialysis on depressive symptoms and postdialysis recovery
      time: interim report from the FREEDOM (Following Rehabilitation, Economics and
      Everyday-Dialysis Outcome Measurements) Study.
AB  - BACKGROUND: Clinical depression and postdialysis fatigue are important concerns
      for patients with kidney failure and can have a negative impact on quality of
      life and survival. STUDY DESIGN: The FREEDOM (Following Rehabilitation, Economics
      and Everyday-Dialysis Outcome Measurements) Study is an ongoing prospective
      cohort study investigating the clinical and economic benefits of daily (6 times
      per week) hemodialysis (HD). In this interim report, as part of an a priori
      planned analysis, we examine the long-term impact of daily HD on depressive
      symptoms, measured using the Beck Depression Inventory (BDI) survey, and
      postdialysis recovery time, measured using a previously validated questionnaire.
      SETTING & PARTICIPANTS: Adult patients initiating daily HD with a planned 12
      month follow-up. OUTCOMES & MEASUREMENTS: The BDI survey and postdialysis
      recovery time question were administered at baseline, and changes were assessed
      at months 4 and 12. RESULTS: 239 participants were enrolled (intention-to-treat
      cohort) and 128 completed the study (per-protocol cohort). Mean age was 52 years,
      64% were men, 55% had an arteriovenous fistula, and 90% transitioned from in
      center HD therapy. In the per-protocol cohort, there was a significant decrease
      in mean BDI score over 12 months (11.2 [95% CI, 9.6-12.9] vs 7.8 [95% CI, 6.5
      9.1]; P<0.001). For robustness, the intention-to-treat analysis was performed,
      yielding similar results. The percentage of patients with depressive symptoms
      (BDI score>10) significantly decreased during 12 months (41% vs 27%; P=0.03).
      Similarly, in the per-protocol cohort, there was a significant decrease in
      postdialysis recovery time over 12 months (476 [95% CI, 359-594] vs 63 minutes
      [95% CI, 32-95]; P<0.001). The intention-to-treat analysis yielded similar
      results. The percentage of patients experiencing prolonged postdialysis recovery
      time (>or=60 minutes) also significantly decreased (81% vs 35%; P=0.001).
      LIMITATIONS: Observational study with lack of control arm. CONCLUSIONS: Daily HD
      is associated with long-term improvement in depressive symptoms and postdialysis
      recovery time.

PMID- 20673591
TI  - Course of cytomegalovirus retinitis in the era of highly active antiretroviral
      therapy: five-year outcomes.
AB  - PURPOSE: To describe the 5-year outcomes of patients with cytomegalovirus (CMV)
      retinitis and AIDS in the era of highly active antiretroviral therapy (HAART).
      DESIGN: Prospective, multicenter, observational study. PARTICIPANTS: A total of
      503 patients with AIDS and CMV retinitis. METHODS: Follow-up every 3 months with
      medical history, ophthalmologic examination, laboratory testing, and retinal
      photographs. Participants were classified as having previously diagnosed CMV
      retinitis and immune recovery (CD4+ T cells >= 100 cells/MUl), previously
      diagnosed retinitis and immune compromise, and newly diagnosed CMV retinitis
      (diagnosis <45 days before enrollment). MAIN OUTCOME MEASURES: Mortality,
      retinitis progression (movement of the border of a CMV lesion >= 1/2 disc
      diameter or occurrence of a new lesion), retinal detachment, immune recovery
      uveitis (IRU), and visual loss (< 20/40 and >= 20/200). RESULTS: Overall
      mortality was 9.8 deaths/100 person-years (PY). Rates varied by group at
      enrollment from 3.0/100 PY for those with previously diagnosed retinitis and
      immune recovery to 26.1/100 PY for those with newly diagnosed retinitis. The rate
      of retinitis progression was 7.0/100 PY and varied from 1.4/100 PY for those with
      previously diagnosed retinitis and immune recovery to 28.0/100 PY for those with
      newly diagnosed retinitis. The rate of retinal detachment was 2.3/100 eye-years
      (EY) and varied from 1.2/100 EY for those with previously diagnosed retinitis and
      immune recovery to 4.9/100 EY for those with newly diagnosed retinitis. The rate
      of IRU was 1.7/100 PY and varied from 1.3/100 PY for those with previously
      diagnosed retinitis and immune recovery at enrollment to 3.6/100 PY for those
      with newly diagnosed retinitis who subsequently experienced immune recovery. The
      rates of visual loss to < 20/40 and to <= 20/200 were 7.9/100 EY and 3.4/100 EY,
      respectively; they varied from 6.1/100 EY and 2.7/100 EY for those with
      previously diagnosed retinitis and immune recovery to 11.8/100 EY and 5.1/100 EY
      for those with newly diagnosed retinitis. Although the event rates tended to
      decline with time, in general, at no time did they reach zero. CONCLUSIONS:
      Despite the availability of HAART, patients with AIDS and CMV retinitis remain at
      increased risk for mortality, retinitis progression, complications of the
      retinitis, and visual loss over a 5-year period. FINANCIAL DISCLOSURE(S):
      Proprietary or commercial disclosure may be found after the references.

PMID- 20673602
TI  - Depression and cognitive function in maintenance hemodialysis patients.
AB  - BACKGROUND: Both depression and cognitive impairment are common in hemodialysis
      patients, are associated with adverse clinical outcomes, and place an increased
      burden on health care resources. STUDY DESIGN: Cross-sectional cohort. SETTING &
      PARTICIPANTS: 241 maintenance hemodialysis patients in the Boston, MA, area.
      PREDICTOR: Depressive symptoms, defined as a Center for Epidemiological Studies
      Depression Scale (CES-D) score >=16. OUTCOME: Performance on a detailed
      neurocognitive battery. RESULTS: Mean age was 63.8 years, 49.0% were women, 21.6%
      were African American, and median dialysis therapy duration was 13.8 months.
      There were 57 (23.7%) participants with significant depressive symptoms. In
      multivariable analysis adjusting for age, sex, education, and other comorbid
      conditions, participants with and without depressive symptoms performed similarly
      on the Mini-Mental State Examination (P = 0.4) and tests of memory. However,
      participants with greater depressive symptoms performed significantly worse on
      tests assessing processing speed, attention, and executive function, including
      Trail Making Test B (P = 0.02) and Digit-Symbol Coding (P = 0.01). Defining
      depression using a CES-D score >=18 did not substantially change results.
      LIMITATIONS: Cross-sectional design, absence of brain imaging. CONCLUSIONS:
      Hemodialysis patients with a greater burden of depressive symptoms perform worse
      on tests of cognition related to processing speed and executive function. Further
      research is needed to assess the effects of treating depressive symptoms on
      cognitive performance in dialysis patients.

PMID- 20673603
TI  - Midaortic syndrome in neurofibromatosis type 1 resulting in bilateral renal
      artery stenosis.
AB  - We describe the case of a 23-year-old white woman with a long history of
      hypertension. She was referred to us 7 years after her initial diagnosis of
      hypertension when her blood pressure control worsened during pregnancy. Clinical
      examination showed an abdominal bruit and weak femoral pulses. Imaging showed
      midaortic syndrome with bilateral renal artery stenosis as the cause of her
      hypertension, and further investigations showed neurofibromatosis type 1 as the
      underlying disorder. Midaortic syndrome, a rare disorder of the abdominal aorta
      that is different from classic coarctation, typically is associated with
      neurofibromatosis. Renal artery stenosis is common, as are weak femoral pulses
      and impaired development of the lower limbs. Because of the rarity of this
      syndrome, only anectodal evidence exists with regard to treatment. Surgery and
      interventional treatment with stent placement in the abdominal aorta have been
      reported, as well as good outcomes with long-term medical management. Our patient
      continues to be healthy without intervention, with reasonable blood pressure
      control and normal kidney function on a 4-drug antihypertensive regimen. We
      discuss midaortic syndrome with a focus on diagnosis, differential diagnosis,
      associated conditions, and management. Nephrologists, radiologists, and
      ultrasonographers should be aware of this rare cause of renovascular
      hypertension.

PMID- 20673604
TI  - Diagnosis and management of severe respiratory acidosis: a 65-year-old man with a
      double-lung transplant and shortness of breath.
AB  - Respiratory acidosis is characterized by a primary increase in whole-body carbon
      dioxide stores caused by a positive carbon dioxide balance. This acid-base
      disorder, if severe, may be life-threatening, therefore requiring prompt
      recognition and expert management. The case presented highlights the essential
      features of the diagnosis and management of respiratory acidosis. A brief
      description of the modifiers of carbon dioxide production, the pathogenesis of
      respiratory acidosis, and an algorithm for assessment and management of this
      disorder is included. Key teaching points include the clinical value of both
      arterial and venous blood gas analyses and the importance of proper recognition
      of a primary respiratory arrest in contrast to primary circulatory arrest when
      managing a patient who requires resuscitation from "cardiorespiratory arrest."

PMID- 20673605
TI  - Defining acute kidney injury in database studies: the effects of varying the
      baseline kidney function assessment period and considering CKD status.
AB  - BACKGROUND: Existing acute kidney injury (AKI) definitions are not well adapted
      for database studies, leading to a great variety of methods used in research.
      Variations in time before hospitalization used to assess baseline kidney function
      when identifying episodes of AKI may lead to different case samples and mortality
      risks in database studies, but the magnitude of these effects is not known. STUDY
      DESIGN: A retrospective cohort study. SETTINGS & PARTICIPANTS: 1,126,636 veterans
      hospitalized at least once within the US Department of Veterans Affairs health
      care system between 2000 and 2005. PREDICTOR: AKI was defined by comparing (using
      ratio [>=1.5] or difference [increase of 0.3-0.5 mg/dL]) the highest serum
      creatinine level during hospitalization with the lowest level during 4 different
      baseline assessment periods (in-hospital only and 3, 6, or 12 months
      preadmission). OUTCOMES & MEASUREMENTS: In-hospital mortality risk was estimated
      using multivariable logistic regression models. RESULTS: Using the ratio
      definition, the cumulative incidence of AKI ranged from 12.5% (in-hospital only)
      to 18.3% (12 months preadmission). Newly added cases had milder AKI and lower
      mortality risk. The discriminative power increased slightly (C statistic
      increased from 0.846 to 0.855; P = 0.001) by extending the baseline period to at
      least 3 months. Both the ratio and difference definitions did not perform well in
      patients with chronic kidney disease stages 4 and 5. LIMITATIONS: Possibility of
      residual confounding and under-representation of women (4.5%). CONCLUSIONS: Many
      additional AKI cases may be identified by extending the baseline assessment
      period; however, added cases may be less severe with lower mortality risk. The
      relative strengths of these biases and combined effects of reducing
      misclassification (identification of more AKI cases) and increasing risk dilution
      (identifying milder cases) may vary across populations. Consensus regarding how
      baseline kidney function should be determined in database studies should be
      reached.

PMID- 20673606
TI  - Features and outcome of patients receiving multiple Medical Emergency Team
      reviews.
AB  - BACKGROUND AND OBJECTIVES: There is no information on the clinical features and
      outcome of patients receiving multiple Medical Emergency Team (MET) reviews.
      Accordingly, we studied the characteristics and outcome of patients receiving one
      MET call and compared them with those receiving multiple MET reviews. DESIGN:
      Retrospective observational study using prospectively collected data. SETTING:
      Tertiary hospital. PATIENTS: Cohort of 1664 patients receiving 2237 MET reviews
      over a 2-year period. MEASUREMENTS AND MAIN RESULTS: We retrieved information
      about patient demographics, reasons for MET review, procedures performed by the
      MET and hospital outcome. We found that 1290 (77.5%) patients received a single
      MET review and 374 (22.5%) received multiple MET reviews (mean 2.5 reviews,
      median 2.0). Multiple MET reviews were more likely to be in surgical patients (p
      < 0.001) and to be due to arrhythmias (p = 0.016). Multiple MET review patients
      were more likely to be admitted for gastrointestinal diseases (p < 0.001), had a
      50% longer hospital stay (p < 0.001) and a 34.6% increase in hospital mortality
      (p < 0.001) compared to single MET review patients. Their odds ratio (OR) for
      mortality was 2.14 (95% C.I.: 1.62-2.83; p < 0.001). After exclusion of patients
      with not for resuscitation (NFR) orders, the OR for mortality was 2.92 (95% C.I.:
      2.10-4.06; p < 0.001). The in-hospital mortality of patients subject to multiple
      MET reviews who were not designated NFR was 34.1%, but only 9.7% of these deaths
      occurred within 48 h of the initial MET review. CONCLUSION: In our hospital, one
      fifth of patients receiving MET calls are subject to multiple MET calls. Such
      patients have identifiable features and have an increased risk of morbidity and
      mortality. Within any rapid response system, such patients should be recognized
      as a higher risk group and receive specific additional attention.

PMID- 20673607
TI  - Short- and long-term outcome of infants born after maternal (pre)-eclampsia,
      HELLP syndrome and thrombophilia: a retrospective, cohort study.
AB  - OBJECTIVES: To investigate the short- and long-term outcome of children born from
      mothers with pre-eclampsia, eclampsia and/or HELLP syndrome, and to determine the
      differences between children born from mothers with and without underlying
      thrombophilic disorder. STUDY DESIGN: Four hundred and nine infants (from 370
      women) born between February 1991 and January 2006 were eligible for evaluation
      and were classified into group A (n = 162) and group B (n = 247). Thirty-four
      infants were not admitted to the hospital. Between-group differences were tested
      with regard to neonatal mortality, morbidity and follow-up measurements for
      neuromotor and mental development at 9 months and 2 years of age, using two
      tailed Student's t-tests, Fisher's exact tests and logistic regression models.
      RESULTS: Of the 409 infants, 44 infants (10.8%; n = 20 group A/n = 24 group B)
      died. The mean gestational age in both groups was 31.9 (SD: 3.5) weeks. Of the
      375 admitted infants 152 (40.5%) were related to a thrombophilic mother and 223
      (59.5%) were not. Six children were lost to follow-up. At 9 months and 2 years of
      age development was assessed in 326 surviving children. At 9 months of age, 193
      (59.2%; n = 66 group A/n = 127 group B) children showed a normal (52% group A
      versus 63.8% group B, P=0.046), 24 (7.4%; n = 9 group A/n = 15 group B) a suspect
      and 14 (4.3%; n = 6 group A, n=8 group B) an abnormal development during follow
      up assessment. Ninety-five children (29.1%; n = 46 group A/n = 49 group B) did
      not have a follow-up assessment. At 2 years of age, 112 children (34.4%; n = 43
      group A/n = 69 group B) had a normal, 21 (6.4%; n = 11 group A/n = 10 group B) a
      suspect and 17 (5.2%; n = 5 group A/n = 12 group B) an abnormal development. 176
      children (54%; n = 70 group A/n = 106 group B) did not have a follow-up
      assessment. CONCLUSION: Short-term outcome was not different between infants from
      mothers with or without thrombophilic disorders. At 9 months of age, the
      probability of having a normal development was significantly lower in children
      born from a mother with an underlying thrombophilic disorder than in those
      without. At 2 years of age, no differences in development were observed.

PMID- 20673608
TI  - The effect of hormonal status on the expression of estrogen and progesterone
      receptor in vaginal wall and periurethral tissue in urogynecological patients.
AB  - OBJECTIVE: Our objective was to study the expression of estrogen receptor (ER)
      isoforms ER alpha (alpha) and ER beta (beta) and of progesterone receptor (PR) in
      the vaginal wall and in periurethral tissue of women who underwent
      urogynecological surgical treatment with reference to estrogen status. STUDY
      DESIGN: The study included 89 patients undergoing vaginal surgery for
      urogynecological conditions. Patients' history and clinical data including
      estrogen status and body mass index (BMI) were evaluated. Biopsies from the
      vaginal wall and from periurethral tissue were obtained during surgery. The
      expression of ER alpha and beta and of PR in vaginal wall and periurethral tissue
      was measured by RT-PCR. RESULTS: Nine patients were premenopausal. Eighty women
      were menopausal, of whom 21 were taking estrogen/progestin replacement therapy
      (HRT), 20 used local estrogen, and 39 had no endocrine treatment. Neither BMI nor
      age had any influence on the expression of ER and PR. Menopausal women showed a
      higher amount of PR expression in vaginal tissue than premenopausal women. Women
      with no endocrine treatment showed a lower amount of ER beta expression in
      vaginal tissue. CONCLUSION: Steroid receptors are expressed in periurethral and
      vaginal tissue. The receptor expression varies with hormonal changes only in
      vaginal tissue. Vaginal tissue seems to be more sensitive to estrogen than
      periurethral tissue.

PMID- 20673609
TI  - Binding of bisphenol A and acrylamide to BSA and DNA: insights into the
      comparative interactions of harmful chemicals with functional biomacromolecules.
AB  - The interactions between bisphenol A (BPA)/acrylamide (AA) and bovine serum
      albumin (BSA)/deoxyribonucleic acid (DNA) was investigated by the equilibrium
      dialysis, fluorophotometry, isothermal titration calorimetry (ITC) and circular
      dichroism (CD). The bindings of BPA and AA to BSA and DNA responded to the
      partition law and Langmuir isothermal model, respectively. The saturation mole
      number of AA was calculated to be 24 per mol BSA and 0.26 per mol DNA-P. All the
      reactions were spontaneous driven by entropy change. BPA stacked into the
      aromatic hydrocarbon groups of BSA and between adjacent basepairs of DNA via the
      hydrophobic effect. The interactions of AA with BSA and DNA induced the formation
      of hydrogen bond and caused changes of their secondary structures. At normal
      physiological condition, 0.100 mmol/l BPA reduced the binding of vitamin B(2) to
      BSA by more than 70%, and 2.8 mmol/l AA by almost one half. This work provides an
      insight into non-covalent intermolecular interaction between organic contaminant
      and biomolecule, helping to elucidate the toxic mechanism of harmful chemicals.

PMID- 20673610
TI  - Enhanced photocatalysis on TiO2 nanotube arrays modified with molecularly
      imprinted TiO2 thin film.
AB  - A molecularly imprinted TiO(2) film was constructed onto the surface of a TiO(2)
      nanotube (NT) array, getting a novel composite TiO(2) catalyst. Compared with
      unmodified TiO(2) NT and the non-imprinted film modified TiO(2) NT, the
      molecularly imprinted film modified TiO(2) NT not only exhibits a much higher
      adsorption capacity for the target contaminant but also shows an enhanced
      photocatalytic activity in degrading the target contaminant. Moreover, the
      molecularly imprinted inorganic semiconductor film is not degraded during
      photocatalysis, owing to its stable physicochemical properties which is superior
      to those of conventional molecularly imprinted organic polymer films.

PMID- 20673611
TI  - Mathematical modeling of cadmium(II) solvent extraction from neutral and acidic
      chloride media using Cyanex 923 extractant as a metal carrier.
AB  - This paper describes experimental work and the mathematical modeling of solvent
      extraction of cadmium(II) from neutral and acidic aqueous chloride media with a
      Cyanex 923 extractant in Exxol D-100. Solvent extraction experiments were carried
      out to analyze the influence of variations in the composition of the aqueous and
      organic phases on the efficiency of cadmium(II) extraction. In neutral and acidic
      chloride conditions, the extraction of cadmium(II) by the organophosphorous
      extractant Cyanex 923 (L) is based on the solvation mechanism of neutral
      H(n)CdCl((2+n)) species and the formation of H(n)CdCl((2+n))L(q) complexes in the
      organic phase, where n=0, 1, 2 and q=1, 2. The mathematical model of cadmium(II)
      extraction was derived from the mass balances and chemical equilibria involved in
      the separation system. The model was computed with the Matlab software. The
      equilibrium parameters for metal extraction, i.e. the stability constants of the
      aqueous Cd-Cl complexes, the formation constants of the acidic Cd-Cl species and
      the metal equilibrium extraction constants, were proposed. The optimized
      constants were appropriate, as there was good agreement when the model was fitted
      to the experimental data for each of the experiments.

PMID- 20673612
TI  - Visceral pain - still an enigma?

PMID- 20673613
TI  - Coherent and incoherent effects on the imaging and scattering process in
      transmission electron microscopy and off-axis electron holography.
AB  - The standard treatment for the different plane wave components of incoming
      electrons in transmission electron microscope imaging is an incoherent
      superposition. However, projectile electrons in transmission electron microscopes
      are localized in space, and therefore have to be described as coherent wave
      packets. Moreover, recent developments towards ultrafast electron microscopy and
      dynamic transmission electron microscopy require a description using highly
      localized wave-packets. Here we will extend the standard stationary modeling of
      the elastic scattering processes in high-resolution microscopy to a fully time
      dependent approach, by using the direct solution of the time-dependent
      Schrodinger equation. We will draw the connection to the detection of coherent
      wave-packets, giving explicit implications for the reconstructed waves in off
      axis electron holography. Additionally the description of incoherent aberrations
      is extended to incorporate the influence of the biprism accurately, leading to a
      modified form of the damping of spatial frequencies.

PMID- 20673614
TI  - Production of biogenic amines "in vitro" in relation to the growth phase by
      Enterobacteriaceae species isolated from traditional sausages.
AB  - Histidine, lysine, ornithine and tyrosine decarboxylase activities were tested in
      79 strains of Enterobacteriaceae (41 of Hafnia alvei, 17 of Serratia
      liquefaciens, 5 of Enterobacter cloacae, 4 of Citrobacter braakii, 2 of Proteus
      vulgaris, 2 of Proteus mirabilis, 2 of Providencia stuartii, 2 of Klebsiella
      terrigena, 1 of Rahnella aquatilis, 1 of Salmonella arizonae, 1 of Citrobacter
      youngae and 1 of Escherichia coli) isolated from Botillo, a Spanish traditional
      sausage. In general, the strains were positive for all four activities, with the
      exception of two strains of H. alvei and the E. coli strain, which did not
      display histidine decarboxylase activity. The strains of P. mirabilis and P.
      stuartii did not exhibit any of the four activities tested. Accumulation of
      putrescine and cadaverine was studied throughout growth of the 75 strains that
      displayed ornithine and lysine decarboxylase activities. Biogenic amines were
      produced particularly in the exponential phase, with maximum accumulation
      occurring after between 12 to 72 h, depending on the biogenic amine and microbial
      species considered. Maximum accumulation of putrescine varied greatly between
      species and within the same species, and ranged from 18 mg/l in the R. aquatilis
      strain to 7325 mg/l in a H. alvei strain. Maximum accumulation of cadaverine
      varied less than that of putrescine, and ranged from 30 mg/l in the R. aquatilis
      strain to 1935 mg/l in a S. liquefaciens strain.

PMID- 20673615
TI  - Effects of extensor synovectomy and excision of the distal ulna in rheumatoid
      arthritis on long-term function.
AB  - PURPOSE: Objective outcomes data after excision of the distal ulna in rheumatoid
      arthritis are lacking. The aim of this study was to evaluate the functional
      results of this surgery in the long term. METHODS: We prospectively collected
      data on range of motion (22 wrists), visual analog pain scores (14 wrists), and
      grip strength measured using a Jamar dynamometer (20 hands) in a group of 23
      patients (26 wrists) preoperatively and at 3 months, 12 months, and a minimum of
      5 years postoperatively (range, 5.3-10.4 y). The Jebsen-Taylor hand function test
      was administered to 9 patients at the same time points. A subgroup of patients
      also underwent extensor carpi radialis longus to extensor carpi ulnaris tendon
      transfer (11 wrists). RESULTS: At one year, there were improvements in wrist
      pronation and supination, which were maintained at final follow-up. Active radial
      deviation decreased significantly at 3 months (p = .01) and one year (p = .02);
      this remained reduced at final follow-up (not significant). Wrist extension and
      active ulnar deviation showed slight improvements by one year, but reduced to
      levels below that measured preoperatively by final follow-up. Wrist flexion was
      significantly reduced at all time points postoperatively. Grip strength showed
      improvement from 10.0 kg (standard deviation [SD] 4.1 kg) preoperatively to 12.5
      kg (SD 4.6 kg) 1 year after surgery and returned to preoperative levels (9.5 kg,
      SD 5.6 kg) by final follow-up. Wrist pain was significantly reduced from a mean
      score of 5 (SD 4) preoperatively to 2 (SD 2) postoperatively (p = .01). The
      Jebsen-Taylor hand function test showed improvements in writing and card turning.
      CONCLUSIONS: In the long term, excision of the distal ulna in rheumatoid patients
      results in an improvement in some aspects of hand function. There is a
      significant (p = .01) reduction in wrist pain but a reduction of wrist flexion.
      TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 20673616
TI  - Detection of highly pathogenic avian influenza virus infection in vaccinated
      chicken flocks by monitoring antibodies against non-structural protein 1 (NS1).
AB  - H5 and H7 highly pathogenic avian influenza virus (HPAIV) represent a major
      global concern in poultries and human health. Avian influenza (AI) vaccines are
      available but not preferred for field applications, primarily because vaccination
      interferes with sero-surveillances of AIV infection. To overcome the problem,
      ELISA systems using non-structural protein 1 (NS1) of AIV as antigens (NS1-ELISA)
      have been developed to measure anti-NS1 antibodies that are raised in AIV
      infected but not in vaccinated chickens. However, some AI-vaccinated chickens
      having a weak anti-virus immune response may subsequently be infected with AIV
      and spread the virus. This raises a concern for the validity of NS1-ELISA to
      detect AIV infection in previously vaccinated chickens. In this study, we
      developed NS1-ELISA and assessed its feasibility to detect HPAIV infection in
      chickens previously immunized with H5 or H7 AI vaccines. The results indicated
      that the NS1-ELISA could identify HPAIV infection in both unvaccinated and
      vaccinated chickens at 1 week after infection in correlation with results from
      time-consuming virus isolation tests. Taken together, the NS1-ELISA system would
      be valuable tool to define HPAIV infection when AI vaccine program is in place.

PMID- 20673617
TI  - The use of MUCT technology to identify skull fracture in a case involving blunt
      force trauma.
AB  - A 40-year-old man was admitted to hospital with a scalp wound but died 22 days
      later after unsuccessful treatment. Initial assessment of the cranial fragments
      removed during surgery revealed fine fracture lines on the endocranial surface,
      and a dark arcuate line on the ectocranial surface. To investigate the extent of
      the fractures a MUCT scan of the fragments was taken, examined in 3D, and
      compared to plain radiographs. Some fractures were found to extend through the
      full thickness of the skull. This case presents a novel application of MUCT
      technology to forensic radiology.

PMID- 20673618
TI  - Determination of cidofovir in human plasma after low dose drug administration
      using high-performance liquid chromatography-tandem mass spectrometry.
AB  - A sensitive and specific method for the determination of cidofovir (CDV) in human
      plasma using high-performance liquid chromatography with tandem mass spectrometry
      (LC-MS/MS) was developed and validated. Plasma samples were processed by a solid
      phase extraction (SPE) procedure using Varian SAX extraction cartridges prior to
      chromatography. The internal standard was (13)C5-Folic acid ((13)C5-FA).
      Chromatography was performed using a Luna C8(2) analytical column, 5 microm, 150
      mm x 3.0 mm, using an isocratic elution with a mobile phase consisting of 43%
      methanol in water containing 12 mM ammonium acetate, at a flow rate of 0.3
      mL/min. The retention times of CDV and (13)C5-FA were 2.1 min and 1.9 min,
      respectively, with a total run time of 5 min. The analytes were detected by a
      Micromass Quattro Micro triple quadrupole mass spectrometer in positive electron
      spray ionization (ESI) mode using multiple reaction monitoring (MRM). The
      extracted ions monitored following MRM transitions were m/z 280.0-->262.1 for CDV
      and m/z 447.0-->294.8 for (13)C5-FA (IS). The assay was linear over the range 20
      1000 ng/mL. Accuracy (101.6-105.7%), intra-assay precision (4.1-5.4%), and inter
      assay precision (5.6-6.8%) were within FDA limits. No significant variation in
      the concentration of CDV was observed with different sample storage conditions.
      This method is simple, adaptable to routine application, and allows easy and
      accurate measurement of CDV in human plasma.

PMID- 20673619
TI  - Perceived dominance in physicians: are female physicians under scrutiny?
AB  - OBJECTIVE: This research aims at identifying how specific physician verbal and
      nonverbal behaviors are related to perceived dominance of female and male
      physicians. METHOD: Analogue patients (163 students) watched videotaped excerpts
      of eight physicians and indicated how dominant they perceived each physician to
      be. RESULTS: Female physicians who spoke more, talked more while doing something
      else, spoke with louder voices, modulated their voices more, were oriented more
      toward the patients, sat at a smaller interpersonal distance, were more
      expansive, and had a more open arm position were perceived as more dominant.
      These relations were significantly more pronounced in female than in male
      physicians. With respect to verbal behavior, not agreeing with the patient,
      structuring the discussion, setting the agenda, and asking questions were related
      to being perceived as significantly more dominant in female than in male
      physicians. CONCLUSION: Patients interpret verbal and nonverbal female and male
      physicians' cues differently. If a behavior contradicts gender stereotypes
      regarding women, this behavior is perceived as particularly dominant in female
      physicians. PRACTICE IMPLICATIONS: To provide optimal care, physicians need to be
      aware of the expectations their patients harbor toward them--especially expected
      behavior related to the gender of the physician.

PMID- 20673620
TI  - Effective training strategies for teaching communication skills to physicians: an
      overview of systematic reviews.
AB  - OBJECTIVE: Physicians need good communication skills to communicate effectively
      with patients. The objective of this review was to identify effective training
      strategies for teaching communication skills to qualified physicians. METHODS:
      PubMED, PsycINFO, CINAHL, and COCHRANE were searched in October 2008 and in March
      2009. Two authors independently selected relevant reviews and assessed their
      methodological quality with AMSTAR. Summary tables were constructed for data
      synthesis, and results were linked to outcome measures. As a result, conclusions
      about the effectiveness of communication skills training strategies for
      physicians could be drawn. RESULTS: Twelve systematic reviews on communication
      skills training programmes for physicians were identified. Some focused on
      specific training strategies, whereas others emphasized a more general approach
      with mixed strategies. Training programmes were effective if they lasted for at
      least one day, were learner-centred, and focused on practising skills. The best
      training strategies within the programmes included role-play, feedback, and small
      group discussions. CONCLUSION: Training programmes should include active,
      practice-oriented strategies. Oral presentations on communication skills,
      modelling, and written information should only be used as supportive strategies.
      PRACTICE IMPLICATIONS: To be able to compare the effectiveness of training
      programmes more easily in the future, general agreement on outcome measures has
      to be established.

PMID- 20673621
TI  - Examination of posttraining supervision of peer counselors in a motivational
      enhancement intervention to reduce drinking in a sample of heavy-drinking college
      students.
AB  - Importance of peer counselor posttraining supervision on motivational
      interviewing (MI) microskills and postintervention drinking outcomes were
      evaluated in a sample of heavy-drinking undergraduate students completing Brief
      Alcohol Screening and Intervention for College Students (BASICS; L.A. Dimeff,
      J.S. Baer, D.R. Kivlahan, & G.A. Marlatt, 1999). Two peer counselor groups were
      trained using identical protocols. Posttraining, one group was randomized to
      receive supervision, whereas the other received no supervision. Groups were
      subsequently compared on MI microskills. College students (n = 122) were randomly
      assigned to either assessment-only control, supervision, or no supervision groups
      and completed a BASICS intervention. Postintervention drinking outcomes were
      examined. Results suggested supervision aided peer counselors in reducing use of
      closed-ended questions. Both treatment groups reduced total drinks per week and
      heavy-drinking behaviors compared to control. No differences on peak blood
      alcohol concentration (BAC) or alcohol-related consequences were observed.
      Differences in supervision did not influence drinking outcomes; however,
      posttraining supervision for peer counselors deficient in MI microskills may be
      needed to improve BASICS fidelity.

PMID- 20673622
TI  - Pro-inflammatory role of Anti-Ro/SSA autoantibodies through the activation of
      Furin-TACE-amphiregulin axis.
AB  - Prolonged inflammation can be detrimental because it may cause host toxicity and
      tissue damage. Indeed, excessive production of inflammatory cytokines is often
      associated with many autoimmune diseases. In this study we demonstrate that the
      anti-Ro/SSA autoantibodies (Abs) stimulate the production of pro-inflammatory
      cytokines IL-6 and IL-8 by human healthy salivary gland epithelial cells (healthy
      SGEC). The secretion of these cytokines is due to amphiregulin (AREG) that is
      overexpressed in healthy SGEC treated with anti-Ro/SSA Abs and in Sjogren's
      syndrome. We have discovered that the up-regulation of AREG occurs through TNF
      alpha produced following anti-Ro/SSA Abs treatment. The gene silencing technique
      was used to study the AREG-TNF-alpha-IL-6/IL-8 secretion pathway, demonstrating
      that: (i) TNF-alpha gene silencing provokes a significant decrease of
      proinflammatory cytokines production and AREG expression in anti-Ro/SSA Abs
      treated healthy SGEC; (ii) AREG gene silencing has a potent inhibitory effect on
      TNF-alpha-induced IL-6 and IL-8 secretion in healthy SGEC treated with anti
      Ro/SSA Abs. These findings indicate that TACE-mediated AREG shedding plays a
      critical role in TNF-alpha-induced IL-6 and IL-8 secretion by the human healthy
      salivary gland epithelial cells, suggesting that this may be one of the possible
      intracellular mechanisms involved in the salivary glands inflammatory response in
      Sjogren's syndrome.

PMID- 20673623
TI  - Nanoscale enzyme reactors in mesoporous carbon for improved performance and
      lifetime of biosensors and biofuel cells.
AB  - Nanoscale enzyme reactors (NERs) of glucose oxidase in conductive mesoporous
      carbons were prepared in a two-step process of enzyme adsorption and follow-up
      enzyme crosslinking. MSU-F-C, a mesoprous carbon, has a bottleneck pore structure
      with mesocellular pores of 26 nm connected with window mesopores of 17 nm. This
      structure enables the ship-in-a-bottle mechanism of NERs, which effectively
      prevents the crosslinked enzymes in mesocellular pores from leaching through the
      smaller window mesopores. This NER approach not only stabilized the enzyme but
      also expedited electron transfer between the enzyme and the conductive MSU-F-C by
      maintaining a short distance between them. In a comparative study with GOx that
      was simply adsorbed without crosslinking, the NER approach was proven to be
      effective in improving the sensitivity of glucose biosensors and the power
      density of biofuel cells. The power density of biofuel cells could be further
      improved by manipulating several factors, such as by adding a mediator, changing
      the order of adsorption and crosslinking, and inserting a gold mesh as an
      electron collector.

PMID- 20673624
TI  - Impedance biosensing using phages for bacteria detection: generation of dual
      signals as the clue for in-chip assay confirmation.
AB  - In the present work, we compare the use of antibodies (Ab) and phages as
      bioreceptors for bacteria biosensing by Electrochemical Impedance Spectroscopy
      (EIS). With this aim, both biocomponents have been immobilised in parallel onto
      interdigitated gold microelectrodes. The produced surfaces have been
      characterised by EIS and Fourier Transform Infra-Red (FTIR) Spectroscopy and have
      been applied to bacteria detection. Compared to immunocapture, detection using
      phages generates successive dual signals of opposite trend over time, which
      consist of an initial increase in impedance caused by bacteria capture followed
      by impedance decrease attributed to phage-induced lysis. Such dual signals can be
      easily distinguished from those caused by non-specific adsorption and/or
      crossbinding, which helps to circumvent one of the main drawbacks of reagentless
      biosensors based in a single target-binding event. The described strategy has
      generated specific detection of Escherichia coli in the range of 10(4)-10(7) CFU
      mL(-1) and minimal interference by non-target Lactobacillus. We propose that the
      utilisation of phages as capture biocomponent for bacteria capture and EIS
      detection allows in-chip signal confirmation.

PMID- 20673625
TI  - Application of oxygen-independent biosensor for testing yeast fermentation
      capacity.
AB  - The pyrroloquinoline quinone (PQQ)-dependent soluble glucose dehydrogenase based
      carbon paste electrodes were investigated and applied for glucose monitoring in
      the oxygen deficient media. Reagentless biosensors possessing a wide linear range
      (up to 5 mM glucose with a detection limit of 0.12 mM) were designed. The oxygen
      insensitive response of the biosensor creates the opportunity to use it as a flow
      through device for continuous monitoring of glucose in media during the wine
      yeast fermentation process. The analysis of glucose assimilation rate by yeast
      strains using the developed biosensor correlated well (R2=0.9938) with convenient
      yeast testing methods.

PMID- 20673626
TI  - Paclitaxel/carboplatin versus topotecan/paclitaxel/carboplatin in patients with
      FIGO suboptimally resected stage III-IV epithelial ovarian cancer a multicenter,
      randomized study.
AB  - OBJECTIVE: The objective of this prospective randomized phase III trial was to
      compare paclitaxel plus carboplatin (PC) versus topotecan plus carboplatin and
      paclitaxel (TPC) in women with suboptimal stage III (residual tumour >1cm) or
      stage IV ovarian cancer to evaluate the survival rate and toxicities. METHODS:
      Eligible for the study were patients aged at least 18 years old with
      histological/cytological diagnosis of FIGO stages III (residual tumour >=1 cm
      after primary surgery)--IV epithelial ovarian cancer. Patients were randomized to
      iv PC on day 1, every 21 days or iv topotecan daily for three days and PC on day
      3, every 21 days. RESULTS: The intention to treat population was made of 326
      patients in total, 170 in the PC group and 156 in the TPC group. The life table
      estimates of survival probabilities at one, three and five years were,
      respectively, 0.94 (95% CI: 0.88-0.97), 0.53 (95% CI: 0.44-0.62) and 0.32 (95%CI:
      0.23-0.42) in the PC group, and 0.92 (95% CI: 0.86-0.95), 0.52 (95% CI: 0.42
      0.61), and 0.32(95%CI: 0.22-0.43) in the TPC group (log-rank test at 5 years:
      ns). The results of the survival analysis based on Cox regression model showed no
      statistically significant differences between groups (p-value: ns). The number of
      subjects with at least one event with possible relationship to study medication
      was 151 (88.8%) in the PC group and 139 (89.1%) in the TPC group (p=ns). In the
      PC group, 79 patients (23.6%) experienced at least one Adverse Event (AE) graded
      as severe and 16 patients (4.8%) at least one life-threatening AE, whilst in the
      TPC group, the number of patients who presented at least one severe or life
      threatening AE was 86 (24%) and 37 (10.3%), respectively. CONCLUSION: The results
      of the present study show that the addition of topotecan to a standard
      paclitaxel/carboplatin regimen in the treatment of advanced epithelial ovarian
      cancer did not result in significant advantages in terms of survival rate. A
      slightly worse toxicity profile for TPC was observed.

PMID- 20673627
TI  - Synthesis and biological evaluation of anilino substituted pyrimidine linked
      pyrrolobenzodiazepines as potential anticancer agents.
AB  - A series of new anilino substituted pyrimidine linked pyrrolo[2,1
      c][1,4]benzodiazepine (PBD) conjugates were prepared and evaluated for their
      anticancer activity. The effects of four promising PBD conjugates on cell cycle
      of cancerous cell line A375 were investigated. These compounds showed the
      characteristic features of apoptosis like enhancement in the levels of p53,
      release of cytochrome c, and cleavage of PARP.

PMID- 20673628
TI  - Labeling of nucleosides with fluorescent 6-chloro-2,3-napthalimide.
AB  - The synthesis and fluorescence properties of new highly fluorescent nucleosides
      are reported. 6-Chloro-2,3-napthalimides activated with benzotriazole and
      chlorine label nucleosides quickly and efficiently in yields of 70-82%: the
      products exhibit quantum efficiencies of 10-94% in solvents of diverse polarity.

PMID- 20673629
TI  - Synthesis of 3,3-diindolyl oxyindoles efficiently catalysed by FeCl3 and their in
      vitro evaluation for anticancer activity.
AB  - A simple and highly efficient method has been developed for the synthesis of 3,3
      diindolyl oxyindoles by the reaction of indoles with isatin or 5-fluoro isatin
      using a catalytic amount (5 mol%) of FeCl(3) at room temperature in a short
      reaction time in high yields. All these compounds were evaluated against a panel
      of five human cancer lines and most of them showed potent cytotoxicity. Compound
      4b showed IC(50) of 4.7 and 5 microM against SK-N-SH and DU-145 cell lines,
      respectively, whereas 4c, 4d, 4f and 4k showed IC(50) of 2.2, 1.2, 3.6 and 3.6
      microM, respectively, against DU-145 cell line. Interestingly, some of the
      compounds are selectively potent in prostate cancer (DU-145) with IC(50) values
      of 1.2-19.6 microM.

PMID- 20673630
TI  - Discovery of a novel class of triazolones as checkpoint kinase inhibitors--hit to
      lead exploration.
AB  - Checkpoint Kinase-1 (Chk1, CHK1, CHEK1) is a Ser/Thr protein kinase that mediates
      cellular responses to DNA-damage. A novel class of Chk1 inhibitors,
      triazoloquinolones/triazolones (TZ's) was identified by high throughput
      screening. The optimization of these hits to provide a lead series is described.

PMID- 20673631
TI  - Dimethylaminopyridine derivatives of lupane triterpenoids are potent disruptors
      of mitochondrial structure and function.
AB  - Development of mitochondrially-targeted drugs is receiving increasing attention
      because of the central roles these organelles play in energy production, reactive
      oxygen generation, and regulation of cell death pathways. Previous studies have
      demonstrated that both natural and synthetic triterpenoids can disrupt
      mitochondrial structure and function. In this study, we tested the ability of a
      number of dimethylaminopyridine (DMAP) derivatives of lupane triterpenoids to
      target mitochochondria in two human melanoma cell lines and an untransformed
      normal fibroblast line. These compounds induced a striking fragmentation and
      depolarization of the mitochondrial network, along with an inhibition of cell
      proliferation. A range of potencies among these compounds was noted, which was
      correlated with the number, position, and orientation of the DMAP groups.
      Overall, the extent of proliferation inhibition mirrored the effectiveness of
      mitochondrial disruption. Thus, DMAP derivatives of lupane triterpenoids can be
      potent mitochondrial perturbants that appear to suppress cell growth primarily
      via their mitochondrial effects.

PMID- 20673632
TI  - Efficient synthesis and biological evaluation of demethyl geranylgeranoic acid
      derivatives.
AB  - Synthetic retinoids have generated in the fields of dermatology and oncology due
      to their potent anti-proliferative and differentiation activities. We efficiently
      synthesized different demethyl geranylgeranoic acid (GGA) analogs, and evaluated
      their biological activities. Among the demethyl analogs synthesized, 3-demethyl
      derivative exhibited the highest anti-proliferative activity in HL-60 cells. In
      addition, a 3-demethyl derivative induced apoptosis more potently than 9Z
      retinoic acid. These activities were due to the high binding affinity of 3
      demethyl derivative for retinoid receptors. We found that, in a conjugated
      polyene system combined with a methyl substituent, the position of the methyl
      played an important role in the regulation of gene transcription and apoptosis
      inducing activity. These results provided useful information on the structure
      activity relationships of GGA derivatives that function as acyclic retinoic acid
      analogs. This information is likely to be useful in the development of new anti
      cancer drugs.

PMID- 20673633
TI  - 6-Alkylquinolone-3-carboxylic acid tethered to macrolides synthesis and
      antimicrobial profile.
AB  - Two series of clarithromycin and azithromycin derivatives with terminal 6
      alkylquinolone-3-carboxylic unit with central ether bond in the linker were
      prepared and tested for antimicrobial activity. Quinolone-linker intermediates
      were prepared by Sonogashira-type C(6)-alkynylation of 6-iodo-quinolone
      precursors. In the last step, 4'' site-selective acylation of 2'-protected
      macrolides was completed with the EDC reagent, which selectively activated a
      terminal, aliphatic carboxylic group in dicarboxylic intermediates. Antimicrobial
      activity of the new series of macrolones is discussed. The most potent compound,
      4''-O-{6-[3-(3-carboxy-1-ethyl-4-oxo-1,4-dihydroquinolin-6-yl)-propoxy]-hexanoyl}
      azithromycin (10), is highly active against bacterial respiratory pathogens
      resistant to macrolide antibiotics and represents a promising lead for further
      investigation.

PMID- 20673634
TI  - Kinetic study for a stress testing of l,l-ethylenedicysteine by ultra-performance
      liquid chromatography/tandem mass spectrometry analysis.
AB  - This study proposed a stress testing to study oxidative stability and estimate
      the potential shelf-life of l,l-ethylenedicysteine (l,l-EC) under normal storage
      temperature condition (20-25 degrees C). l,l-EC was detected as a function of
      time at four different temperatures by ultra-performance liquid
      chromatography/tandem mass spectrometry (UPLC/MS/MS). The degradation of l,l-EC
      followed the first order kinetics, and the temperature-dependent kinetics was
      well described by the linear Arrhenius equation. The activation energy (E(a)) was
      calculated, and the shelf-life at 25 and 4 degrees C was predicted. The results
      are useful for the proper storage and quality evaluation of l,l-EC.

PMID- 20673635
TI  - Developmental myosin heavy chain mRNA in masseter after orthognathic surgery: a
      preliminary study.
AB  - INTRODUCTION: A microarray study showed an increase of developmental myosin heavy
      chain (MyHC) mRNA in the masseter muscle after surgery. The aim of the study was
      to determine the expression of the embryonic MYH3 and perinatal MYH8 for use as
      potential marker for muscle adaptation after orthognathic surgery. MATERIAL AND
      METHODS: 24 adult patients with a prognathic (11) or retrognathic (13) mandible
      were involved in the study. 192 biopsies were taken from two parts of the muscles
      presurgically and 6 months following. The expression of MYH3 and MYH8 were
      quantified using real-time polymerase chain reaction (RT-PCR). Absolute
      quantification was done by CT-values. RESULTS: MYH3 was up-regulated in
      prognathia (8.5, P<0.001) and in retrognathia (2.8, P<0.043). MYH8 was up
      regulated in retrognathia only (4.0, P<0.063) and down-regulated in prognathia (
      1.6). MYH3 values correlated in retrognathic patients (P<0.005) before and after
      surgery. CONCLUSION: MYH3 and MYH8 could play a role in functional adaptation
      after orthognathic surgery and orofacial orthopaedics.

PMID- 20673636
TI  - Duplicated, translocated maxilla and upper lip: a case report of a rare
      congenital anomaly.
AB  - A 3-month-old male patient presented to the maxillofacial department in Al-Amiri
      Dental Center, Kuwait, with a facial deformity. There was no family history of
      any systemic illness or abnormalities nor consanguinity. On examination; the
      patient had a transverse incomplete facial cleft on the right cheek, the maxilla
      and the upper lip were duplicated and translocated to the right lower jaw and
      lip, with all components of mucosa as well as a complete compliment of deciduous
      teeth. There was unilateral macrosomia as well as cleft of the secondary palate
      and triple uvulae. The mandible had restricted mobility. Photographs and a
      Computerized Axial tomogram (CAT scan) were taken and a complete work up to
      exclude congenital cardiac disease was also done. The surgical approach, and
      possible future operations were explained in detail and discussed with the
      parents. Their consent was taken.

PMID- 20673637
TI  - A modified midfacial degloving approach for the treatment of unilateral paranasal
      sinus tumours.
AB  - PURPOSE: The midfacial degloving approach (MFDA) is the primary option for the
      removal of benign and malignant sinonasal tumours. However, the classic MFDA does
      not compensate for the fact that most benign and malignant paranasal sinus (PNS)
      tumours are unilateral and the incisions may lead to some unnecessary
      complications?. Surgical exposure is limited to the upper and deep part of the
      PNS. Modifications of the classical MFDA that minimize complications and improve
      surgical field exposure are warranted. PATIENTS: The medical records of 27
      consecutive patients who had undergone surgery using a modified MFDA for
      treatment of unilateral benign or malignant tumours from 2000 to 2006, were
      reviewed. RESULTS: We developed and performed a modified MFDA utilizing a
      hemigingivobuccal incision, a transfixion incision, mucosal detachment of the
      pyriform aperture and separation of the upper lateral cartilage from the nasal
      bone in 27 patients with unilateral benign (85%) or malignant (15%) PNS
      neoplasms. Adequate surgical exposure was achieved in all cases. No technical
      problems and no intraoperative complications related to the surgical procedure
      were encountered. CONCLUSION: Our modified MFDA provides sufficient surgical
      exposure for the removal of unilateral malignant or benign PNS tumours with few
      surgical or cosmetic complications.

PMID- 20673638
TI  - Hypoglossia-hypodactyly syndrome in a newborn.
AB  - Hypoglossia-hypodactyly syndrome is characterised by small tongue associated with
      limb deficiency. It is an extremely rare condition with around 30 cases reported
      in world literature. We report a case of hypoglossia-hypodactyly syndrome that in
      addition to features already described also had supernumerary nipples,
      microcephaly and micropenis with cryptorchidism. Hypodactyly was symmetrical in
      all four limbs. These features have not been reported previously.

PMID- 20673640
TI  - Bronchoalveolar lavage neutrophilia in acute lung allograft rejection and
      lymphocytic bronchiolitis.
AB  - BACKGROUND: Acute cellular rejection and lymphocytic bronchiolitis can impair
      allograft function after lung transplant (LTx). Both may be refractory to
      corticosteroid treatment. We hypothesized that bronchoalveolar lavage (BAL)
      neutrophilia may be increased in either acute rejection or lymphocytic
      bronchiolitis or may increase with increasing histologic severity. METHODS: All
      consecutive BAL with subsequent transbronchial biopsy (TBB) specimens, performed
      in 339 LTx recipients from 2001 to 2008, were retrospectively analyzed. TBB
      specimens were classified according to histologic grade with analysis of BAL
      total cell count and cell differentials. RESULTS: The analysis included 768 TBB
      specimens. After adjustment for possible confounders, BAL total cell count
      significantly increased both with grade A or B severity (p < 0.0001). A higher A
      grade was characterized by a significant increase in BAL lymphocytosis and
      neutrophilia (p < 0.0001), whereas for higher B grades, only a more prominent BAL
      neutrophilia was seen (p < 0.0001). CONCLUSIONS: Higher grade A, but,
      particularly, higher grade B severity scores are characterized by increased BAL
      neutrophilia.

PMID- 20673641
TI  - Value of 3.0 T MR imaging in refractory partial epilepsy and negative 1.5 T MRI.
AB  - BACKGROUND: High-field 3.0 T MR scanners provide an improved signal-to-noise
      ratio which can be translated in higher image resolution, possibly allowing
      critical detection of subtle epileptogenic lesions missed on standard-field 1.0
      1.5 T MRIs. In this study, the authors explore the potential value of re-imaging
      at 3.0 T patients with refractory partial epilepsy and negative 1.5 T MRI.
      METHODS: We retrospectively identified all patients with refractory partial
      epilepsy candidate for surgery who had undergone a 3.0 T MR study after a
      negative 1.5 T MR study. High-field 3.0 T MRIs were reviewed qualitatively by
      neuroradiologists experienced in interpreting epilepsy studies with access to
      clinical information. Relevance and impact on clinical management were assessed
      by an epileptologist. RESULTS: Between November 2006 and August 2009, 36 patients
      with refractory partial epilepsy candidate for surgery underwent 3.0 T MR study
      after a 1.5 T MR study failed to disclose a relevant epileptogenic lesion. A
      potential lesion was found only in two patients (5.6%, 95% CI: 1.5-18.1%). Both
      were found to have hippocampal atrophy congruent with other presurgical
      localization techniques which resulted in omission of an invasive EEG study and
      direct passage to surgery. CONCLUSIONS: The frequency of detection of a new
      lesion by re-imaging at 3.0 T patients with refractory partial epilepsy candidate
      for surgery was found to be low, but seems to offer the potential of a
      significant clinical impact for selected patients. This finding needs to be
      validated in a prospective controlled study.

PMID- 20673639
TI  - Effects of supercharging reagents on noncovalent complex structure in
      electrospray ionization from aqueous solutions.
AB  - The effects of two supercharging reagents, m-nitrobenzyl alcohol (m-NBA) and
      sulfolane, on the charge-state distributions and conformations of myoglobin ions
      formed by electrospray ionization were investigated. Addition of 0.4% m-NBA to
      aqueous ammonium acetate solutions of myoglobin results in an increase in the
      maximum charge state from 9+ to 19+, and an increase in the average charge state
      from 7.9+ to 11.7+, compared with solutions without m-NBA. The extent of
      supercharging with sulfolane on a per mole basis is lower than that with m-NBA,
      but comparable charging was obtained at higher concentration. Arrival time
      distributions obtained from traveling wave ion mobility spectrometry show that
      the higher charge state ions that are formed with these supercharging reagents
      are significantly more unfolded than lower charge state ions. Results from
      circular dichroism spectroscopy show that sulfolane can act as chemical
      denaturant, destabilizing myoglobin by ~1.5 kcal/mol/M at 25 degrees C. Because
      these supercharging reagents have low vapor pressures, aqueous droplets are
      preferentially enriched in these reagents as evaporation occurs. Less evaporative
      cooling will occur after the droplets are substantially enriched in the low
      volatility supercharging reagent, and the droplet temperature should be higher
      compared with when these reagents are not present. Protein unfolding induced by
      chemical and/or thermal denaturation in the electrospray droplet appears to be
      the primary origin of the enhanced charging observed for noncovalent protein
      complexes formed from aqueous solutions that contain these supercharging
      reagents, although other factors almost certainly influence the extent of
      charging as well.

PMID- 20673642
TI  - Quadrupolar-coupling-specific binomial pulse sequences for in vivo 23Na NMR and
      MRI.
AB  - Aimed at selective detection of (23)Na with specific quadrupolar couplings for in
      vitro NMR and MRI, we present a series of quadrupolar binomial pulse sequences
      offering high specificity with respect to the quadrupolar couplings of the
      excited species. It is demonstrated that pulse sequences with an increasing
      number of elements, e.g., 11, 121, 1331, 14641, and 15101051, with the units
      representing flip angles smaller than the 90 degrees pulses typically encountered
      in binomial spin-1/2 solvent suppression experiments, and different phase
      combinations may provide a high degree of flexibility with respect to quadrupolar
      coupling selectivity and robustness towards rf inhomogeneity. This may facilitate
      efficient separation of, for example, intra and extracellular (23)Na in tissues
      with efficient control of the excitation (or suppression) of central as well as
      satellite transitions through on- and off-resonance irradiation. The pulse
      sequences are described in terms of their analogy to binomial liquid-state NMR
      solvent suppression experiments and demonstrated numerically and experimentally
      through NMR and MRI experiments on a 7 T horizontal small-bore animal magnet
      system.

PMID- 20673643
TI  - Pneumatic switched angle spinning NMR probe with capacitively coupled double
      saddle coil.
AB  - Switched angle spinning (SAS) experiments can be used for generating isotropic
      anisotropic correlations in oriented samples in a single experiment. In order for
      these methods to become widespread, specialized hardware is required. Here we
      describe the electronic and mechanical design and performance of a double
      resonance SAS probe. Unlike many previous SAS probe implementations, the focus
      here is on systems where the dipolar couplings are partially averaged by
      molecular motion. This probe has a moving double saddle coil capacitively coupled
      to the stationary circuit. Angle switching is accomplished by a steam engine-type
      pneumatic mechanism. The speed and stability of the switching hardware for SAS
      experiments are demonstrated using spectra of model compounds.

PMID- 20673644
TI  - The metabolic syndrome as a predictor of incident diabetes and cardiovascular
      events in the Health 2000 Study.
AB  - AIM: The study aimed to examine the role of the metabolic syndrome (MetS) as a
      predictor of incident cardiovascular disease (CVD) events and incident diabetes,
      and to compare the various definitions of MetS. METHODS: The population-based
      Health 2000 Study included 6105 individuals, aged 30-79 years, followed-up for 7
      years. CVD during follow-up was defined as coronary death, acute myocardial
      infarction, coronary revascularization or stroke. MetS was defined according to
      the International Diabetes Federation (IDF), the 2005 National Cholesterol
      Education Program-Adult Treatment Panel III (ATP III), the World Health
      Organization (WHO) and the new Harmonization definitions. The Bayesian
      information criterion (BIC) was used to compare different Cox proportional
      hazards regression models. RESULTS: The highest prevalence estimates of MetS at
      baseline were observed with the Harmonization definition: 47.8% in men and 40.7%
      in women. During the follow-up, 238 cases of incident CVD and 172 cases of
      incident diabetes were observed. All definitions of MetS were significant
      predictors for incident CVD and diabetes. BIC suggested that the new
      Harmonization definition of MetS as one entity was a better predictor of the CVD
      endpoint than the sum of its components, but not for diabetes. Also, the
      Harmonization definition of MetS was a better predictor of CVD than the
      Framingham equation in women, but not in men. CONCLUSION: Irrespective of
      definition, MetS is a significant predictor of incident CVD events and incident
      diabetes. Also, the new Harmonization definition may be a better predictor of
      incident CVD than the sum of its components.

PMID- 20673645
TI  - Transmission of pandemic influenza A (H1N1) 2009 within households: Edmonton,
      Canada.
AB  - BACKGROUND: In April 2009, a novel influenza A, subtype H1N1, now referred to as
      the Pandemic (H1N1) 2009 virus (pH1N1), began circulating in countries around the
      world. Describing the transmission characteristics of this novel influenza A
      virus is important to predict current, and future, disease spread. The Public
      Health response to the first wave of pH1N1 in Alberta focused on the
      identification and management of secondary cases within households. OBJECTIVES:
      The purpose of this study was to describe transmission characteristics of pH1N1
      in households in Edmonton, the capital city of Alberta, during the first wave,
      and to identify the serial interval and secondary attack rate (SAR) in this
      setting. STUDY DESIGN: This is a prospective analysis of pH1N1 household
      transmission within 87 urban Canadian households between April 30 and June 9,
      2009; with each household having at least one laboratory-confirmed case. The
      secondary attack rate was calculated in the 262 household contacts using a
      weighted average by number of susceptible individuals in each household. The
      serial interval, or time to illness in secondary cases, was analyzed using
      survival analysis with a Weibull model. RESULTS: Within the 87 households, 42
      (48.3%) had no secondary cases develop; 25 (28.7%) had one secondary case
      develop; and 20 (22.9%) had more than one secondary case develop. The secondary
      attack rate did not decrease with increasing household size and households with
      two members exhibited the lowest secondary attack rate at 14.1%. Children under
      the age of 19, and individuals with an underlying medical condition, were at
      increased risk (p<0.05) of becoming a secondary case. The overall secondary
      attack rate among the 262 susceptible household contacts was 30.2% (95% CI: 12.6
      52.2). The median serial interval for pH1N1 transmission was 3.4 days (95% CI:
      2.9-3.9). CONCLUSIONS: The identified transmission characteristics of pH1N1 among
      Canadian households differ slightly from other previously reported North American
      estimates, but are in keeping with historical transmission rates of pandemic
      influenza viruses.

PMID- 20673646
TI  - Reorganization of the primary somatosensory cortex during stroke recovery.
AB  - OBJECTIVE: Animal and human studies have indicated that stroke induces
      reorganization of the motor and somatosensory cortices. We aimed to clarify how
      changes in the primary somatosensory (SI) cortex correlate with stroke recovery.
      METHODS: We recorded somatosensory evoked fields (SEFs) with
      magnetoencephalography from 15 patients with stroke affecting upper extremity
      motor function. The size of the hand representation in the SI cortex was
      calculated from the Euclidean distance between the sources of SEFs to thumb and
      little finger tactile stimulation. The measurements were made at 1-7 days (T0),
      at 1 (T1), and at 3 months (T2) after stroke, with concomitant evaluation of hand
      function. RESULTS: The affected hand function was improved at T1 and T2 compared
      with T0 (p<0.01). At T1, the SI hand representation in the affected hemisphere
      was enlarged compared with T0 or T2 (12.6+/-0.8 at T1 vs. 9.6+/-0.8 mm at T0 and
      10.2+/-0.8 at T2, p<0.05). In patients with subcortical infarction, the increase
      in cortical representation at T1 correlated strongly with impairment of hand
      function (r=0.8, p<0.01). CONCLUSION: Reorganization of the SI cortex provokes a
      transient enlargement of the hand representation that normalizes as hand
      functions are regained. SIGNIFICANCE: The temporal evolution of plastic changes
      during stroke recovery might be useful in evaluating motor recovery.

PMID- 20673647
TI  - Clinical correlates of frontal intermittent rhythmic delta activity (FIRDA).
AB  - OBJECTIVES: To investigate the clinical correlates of frontal intermittent
      rhythmic delta activity (FIRDA). METHODS: we prospectively assessed all EEG
      studies recorded in our center over 3 months for the presence of frontal
      intermittent rhythmic delta activity (FIRDA). The FIRDA group was compared with a
      randomly selected control group from among EEGs recorded during the same period.
      Comparisons among FIRDA and non-FIRDA groups were performed using uni- and multi
      variate analyses. RESULTS: We found 36 patients with FIRDA among 559 EEG
      recordings (6%); the control group consisted of 80 subjects. While epilepsy was
      more frequent in the control group, structural brain lesions and encephalopathy
      were independently associated with the occurrence of FIRDA, but we could not
      identify any specific etiology. Asymmetric FIRDA was associated with an
      underlying brain lesion. Occasionally, FIRDA was recorded in otherwise healthy
      subjects during hyperventilation. CONCLUSION: FIRDA appears more common than
      previously reported, and is associated with a wide range of lesions and
      encephalopathic conditions. SIGNIFICANCE: FIRDA occurrence should prompt
      investigations for toxic-metabolic disturbances and for structural lesions
      (particularly if asymmetric), but does not suggest an epileptic predilection.

PMID- 20673649
TI  - Electronic media use and sleep in school-aged children and adolescents: A review.
AB  - Electronic media have often been considered to have a negative impact on the
      sleep of children and adolescents, but there are no comprehensive reviews of
      research in this area. The present study identified 36 papers that have
      investigated the relationship between sleep and electronic media in school-aged
      children and adolescents, including television viewing, use of computers,
      electronic gaming, and/or the internet, mobile telephones, and music. Many
      variables have been investigated across these studies, although delayed bedtime
      and shorter total sleep time have been found to be most consistently related to
      media use. A model of the mechanisms by which media use may affect sleep is
      presented and discussed as a vehicle for future research.

PMID- 20673648
TI  - Effects of homeopathic medicines on polysomnographic sleep of young adults with
      histories of coffee-related insomnia.
AB  - BACKGROUND: Homeopathy, a common form of alternative medicine worldwide, relies
      on subjective patient reports for diagnosis and treatment. Polysomnography offers
      a modern methodology for evaluating the objective effects of taking homeopathic
      remedies that clinicians claim exert effects on sleep quality in susceptible
      individuals. Animal studies have previously shown changes in non rapid eye
      movement sleep with certain homeopathic remedies. METHODS: Young adults of both
      sexes (ages 18-31) with above-average scores on standardized personality scales
      for either cynical hostility or anxiety sensitivity (but not both) and a history
      of coffee-induced insomnia participated in the month-long study. At-home
      polysomnographic recordings were obtained on successive pairs of nights once per
      week for a total of eight recordings (nights 1, 2, 8, 9, 15, 16, 22, 23).
      Subjects (N=54) received placebo pellets on night 8 (single-blind) and verum
      pellets on night 22 (double-blind) in 30c doses of one of two homeopathic
      remedies, Nux Vomica or Coffea Cruda. Subjects completed daily morning sleep
      diaries and weekly Pittsburgh sleep quality index scales, as well as profile of
      mood states scales at bedtime on polysomnography nights. RESULTS: Verum remedies
      significantly increased PSG total sleep time and NREM, as well as awakenings and
      stage changes. Changes in actigraphic and self-rated scale effects were not
      significant. CONCLUSIONS: The study demonstrated the feasibility of using in
      home, all-night sleep recordings to study homeopathic remedy effects. Findings
      are similar though not identical to those reported in animals with the same
      remedies. Possible mechanisms include initial disruption of the nonlinear
      dynamics of sleep patterns by the verum remedies.

PMID- 20673650
TI  - Radiological predictors of recurrent primary spontaneous pneumothorax following
      non-surgical management.
AB  - BACKGROUND: Studies to date have not identified any reliable predictors for
      recurrence of primary spontaneous pneumothorax (PSP) on plain chest radiograph
      (CXR). The aim of this study was to assess whether abnormalities on CXR at first
      presentation of PSP can be used to predict recurrence of PSP. METHOD: The study
      included all patients admitted to The Canberra Hospital between 1998 and 2004.
      CXRs taken at initial presentation were reviewed retrospectively by an
      independent radiologist. Radiological abnormalities on CXR included: pleural
      thickening: blebs/bullae; pleural irregularities and pleural adhesions. RESULTS:
      One hundred patients were followed up for a mean duration of 57 months. The total
      rate of recurrence was 54%. Multivariate analysis found that the presence of an
      abnormality (irrespective of the type) increased the likelihood of recurrence and
      the risk of recurrence increased with each additional abnormality. Patients
      having one, two and three or more abnormalities were 3.0 (95% CI=2.09, 3.91,
      p=0.018), 5.3 (95% CI=4.47, 6.13, p<0.001) and 12.6 (95% CI=11.57, 13.63,
      p<0.001) times more likely to develop recurrence respectively. CONCLUSION: In
      view of these results we now offer surgical treatment at first presentation PSP
      in patients in whom we identify two or more radiological abnormalities on CXR.

PMID- 20673651
TI  - Determination of ginsenoside Rg3 in human plasma and urine by high performance
      liquid chromatography-tandem mass spectrometry.
AB  - Here we report a method capable of quantifying ginsenoside Rg3 in human plasma
      and urine. The method was validated over linear range of 2.5-1000.0ngmL(-1) for
      plasma and 2.0-20.0ngmL(-1) for urine using ginsenoside Rg1 as I.S. Compounds
      were extracted with ethyl acetate and analyzed by HPLC/MS/MS (API-4000 system
      equipped with ESI(-) interface and a C(18) column). The inter- and intra-day
      precision and accuracy of QC samples were <or=8.5% relative error and were
      <or=14.4% relative standard deviation for plasma; were <or=5.6% and <or=13.3% for
      urine. The Rg3 was stable after 24h at room temperature, 3 freeze/thaw cycles and
      131 days at -30 degrees C. This method has been applied to pharmacokinetic study
      of ginsenoside Rg3 in human.

PMID- 20673652
TI  - DNA overstretched state: S-DNA form or force-induced melting? Comment on
      "Biophysical characterization of DNA binding from single molecule force
      measurements" by Mark C. Williams et al.

PMID- 20673653
TI  - Single molecule force measurements: insights from molecular simulations. Comment
      on "Biophysical characterization of DNA binding from single molecule force
      measurements" by Kathy R. Chaurasiya et al.

PMID- 20673654
TI  - Does neonatal and infant neurodevelopmental morbidity of multiples and singletons
      differ?
AB  - The mortality and morbidity of twins may differ from that in singletons because
      of the greater incidence of intrauterine growth restriction, higher rates of
      prematurity, zygosity and even from the presence of a same age sibling during
      childhood. Early outcomes appear poorer for twins, but any differences are lost
      when corrections for gestation and growth restriction are made. Some studies show
      poorer cognitive outcomes for twins; larger and more recent studies show small
      but significant differences even when confounders are taken into account.
      Cerebral palsy rates are considerably higher in twins, especially with the death
      of a co-twin. Behavioural outcomes are broadly similar in twins and singletons,
      with growth and gestation being more important determinants than plurality.
      Psychiatric symptoms again are broadly similar, although there appears to be a
      reduced risk of suicide in twins.

PMID- 20673655
TI  - Preventive effect of botulinum toxin A in microanastomotic thrombosis: a rabbit
      model.
AB  - BACKGROUND: Microvascular free tissue transfers play an important role in the
      reconstruction of body defects. Various aetiologies lead to vascular thrombosis
      and free-flap failure. In this study, the effects of botulinum toxin A on vessel
      diameters and prevention of anastomotic thrombosis were studied in a blinded
      vasospasm model in rabbits. METHODS: One side of 16 adult rabbit ears was pre
      treated with botulinum toxin type A, and normal saline injections were performed
      as control in the contralateral side. Seven days later, vessel diameters were
      measured in both the groups; the vessels were then cut and reanastomosed after
      vasospastic challenge and vessel patencies were evaluated. RESULTS: Both artery
      and vein diameters were significantly larger in the botulinum toxin A group
      (P=0.002 and < 0.001, respectively). The patency rate of arterial and venous
      anastomosis was significantly higher in the neurotoxin pre-treated group (P=0.038
      and 0.003, respectively). CONCLUSION: This study shows that pre-treatment with
      botulinum toxin type A is associated with a lower rate of arterial and venous
      thrombosis in rabbit-model microanastomosis. Further studies are necessary to
      evaluate its ability to decrease vasospasm and thrombosis in free-flap survival
      of humans.

PMID- 20673656
TI  - Atypical fibroxanthoma of the scalp following hair transplantation in a 35-year
      old male.
AB  - Atypical fibroxanthoma (AFX) is an uncommon spindle cell neoplasm of the elderly.
      This case report presents an atypical case of AFX of the scalp 8 years after hair
      transplantation in a 35-year-old male patient. Possible synergistic effects of
      previous sun exposure radiation to the scalp, together with the thermal and
      radiation injury of carbon dioxide (CO(2)) laser, might explain the mechanisms of
      the development of AFX at such an early age. To the best of our knowledge, this
      case report is the first description in the medical literature of development of
      skin malignancy on a hair-transplanted scalp.

PMID- 20673657
TI  - Trends in mortality and mean age at death from lung cancer in Austria (1975
      2007).
AB  - OBJECTIVE: To investigate trends in mortality and mean age at death from lung
      cancer (MADLC) compared to mean age at death from all causes (MAD) over the
      period 1975 - 2007 in Austria. Results are assessed with respect to secular
      trends in smoking habits. METHODS: MAD and MADLC were computed by year and gender
      as the expected value of a fitted Weibull distribution. Age-period-cohort effects
      on lung cancer death rates were estimated by hierarchical Poisson models.
      RESULTS: In females MADLC was on average about 2 years higher than in males and
      tended to decrease since the mid 1980s, while after the mid 1990s MADLC in males
      increased such that the difference between men and women shrank to about half a
      year in 2007. Females dying from lung cancer lost about 6 years of life during
      the late 1970s but more than 10 years after 2000, while males lost 2 years in the
      1970s and 5 years after 2000. Males demonstrated a decreasing risk with
      increasing year of birth, with the exception of cohorts born during or
      immediately after the World Wars that showed peak relative risks (RR). Females
      did not show pronounced birth cohort effect except for a peak RR for cohorts born
      during and after World War II. CONCLUSIONS: MADLC provides additional information
      about secular trends in addition to incidence data. The declining trend of MADLC
      in females and in males up to the mid 1990s points to a change of smoking habits
      with an earlier onset of smoking in both genders. The subsequent increase in
      males during the last decade may be attributed to an increasing proportion of
      quitters because smoking cessation delays onset of lung cancer.

PMID- 20673658
TI  - Production of 5-hydroxymethylfurfural in ionic liquids under high fructose
      concentration conditions.
AB  - Acid-promoted, selective production of 5-hydroxymethylfurfural (HMF) under high
      fructose concentration conditions was achieved in ionic liquids (ILs) at 80
      degrees C. A HMF yield up to 97% was obtained in 8min using 1-butyl-3
      methylimidazolium chloride ([C(4)mim]Cl) catalyzed with 9mol% hydrochloric acid.
      More significantly, an HMF yield of 51% was observed when fructose was loaded at
      a high concentration of 67wt% in [C(4)mim]Cl. Water content below 15.4% in the
      system had little effect on HMF yield, whereas a higher water content was
      detrimental to both reaction rate and HMF yield. In situ NMR analysis suggested
      that the transformation of fructose to HMF was a highly selective reaction that
      proceeded through the cyclic fructofuranosyl intermediate pathway. This work
      increased our capacity to produce HMF, and should be valuable to facilitate cost
      efficient conversion of biomass into biofuels and bio-based products.

PMID- 20673659
TI  - Speech errors of amnesic H.M.: unlike everyday slips-of-the-tongue.
AB  - Three language production studies indicate that amnesic H.M. produces speech
      errors unlike everyday slips-of-the-tongue. Study 1 was a naturalistic task: H.M.
      and six controls closely matched for age, education, background and IQ described
      what makes captioned cartoons funny. Nine judges rated the descriptions blind to
      speaker identity and gave reliably more negative ratings for coherence,
      vagueness, comprehensibility, grammaticality, and adequacy of humor-description
      for H.M. than the controls. Study 2 examined "major errors", a novel type of
      speech error that is uncorrected and reduces the coherence, grammaticality,
      accuracy and/or comprehensibility of an utterance. The results indicated that
      H.M. produced seven types of major errors reliably more often than controls:
      substitutions, omissions, additions, transpositions, reading errors, free
      associations, and accuracy errors. These results contradict recent claims that
      H.M. retains unconscious or implicit language abilities and produces spoken
      discourse that is "sophisticated," "intact" and "without major errors." Study 3
      examined whether three classical types of errors (omissions, additions, and
      substitutions of words and phrases) differed for H.M. versus controls in basic
      nature and relative frequency by error type. The results indicated that
      omissions, and especially multi-word omissions, were relatively more common for
      H.M. than the controls; and substitutions violated the syntactic class regularity
      (whereby, e.g., nouns substitute with nouns but not verbs) relatively more often
      for H.M. than the controls. These results suggest that H.M.'s medial temporal
      lobe damage impaired his ability to rapidly form new connections between units in
      the cortex, a process necessary to form complete and coherent internal
      representations for novel sentence-level plans. In short, different brain
      mechanisms underlie H.M.'s major errors (which reflect incomplete and incoherent
      sentence-level plans) versus everyday slips-of-the tongue (which reflect errors
      in activating pre-planned units in fully intact sentence-level plans).
      Implications of the results of Studies 1-3 are discussed for systems theory,
      binding theory and relational memory theories.

PMID- 20673660
TI  - Sequential hair mercury in mothers and children from a traditional riverine
      population of the Rio Tapajos, Amazonia: seasonal changes.
AB  - Riverine populations of the Brazilian Amazon depend on fish for their principal
      source of protein, which changes in availability with seasonal fluctuations in
      the aquatic ecosystem. We report seasonal (high and low waters) and interannual
      changes in total mercury and methylmercury concentrations in hair of subsistence
      fish-eaters from a traditional riverine village on the banks of the Rio Tapajos
      in the Brazilian Amazonia. Retrospective exposure assessment was conducted from
      hair concentrations in segments representative of 2 years. A total of 32 mothers
      and their 51 children were studied. They reported high fish consumption (4-14
      times a week). Ranges of total mercury and methylmercury concentrations in hair
      were 1.0-51.0 and 0.5-41.4microgg(-1), with means of 12.4 and 10.2microgg(-1),
      respectively. The relative mean value for methylmercury was 80%. There was a
      significant correlation between mothers and children for both total-Hg (r=0.4826;
      P=0.003) and methyl-Hg (r=0.5214; P=0.004). Mercury concentrations along hair
      strands of individuals showed significant variation coinciding with seasonal high
      and low waters. The changes in the aquatic environment impacted fish species
      availability, which is reflected in the total and MeHg concentrations in hair.

PMID- 20673661
TI  - [Being a doctor in Massachusetts General Hospital Harvard Medical School].

PMID- 20673662
TI  - [The best srategies to optimize lipid control: increasing statins dose or
      ezetimibe coadministration?].

PMID- 20673663
TI  - [Faintness at extreme altitude].

PMID- 20673664
TI  - [Characteristics of acute pyelonephritis that require hospital admission].

PMID- 20673665
TI  - In vivo tibial stiffness is maintained by whole bone morphology and cross
      sectional geometry in growing female mice.
AB  - Whole bone morphology, cortical geometry, and tissue material properties modulate
      skeletal stresses and strains that in turn influence skeletal physiology and
      remodeling. Understanding how bone stiffness, the relationship between applied
      load and tissue strain, is regulated by developmental changes in bone structure
      and tissue material properties is important in implementing biophysical
      strategies for promoting healthy bone growth and preventing bone loss. The goal
      of this study was to relate developmental patterns of in vivo whole bone
      stiffness to whole bone morphology, cross-sectional geometry, and tissue
      properties using a mouse axial loading model. We measured in vivo tibial
      stiffness in three age groups (6, 10, 16 wk old) of female C57Bl/6 mice during
      cyclic tibial compression. Tibial stiffness was then related to cortical
      geometry, longitudinal bone curvature, and tissue mineral density using
      microcomputed tomography (microCT). Tibial stiffness and the stresses induced by
      axial compression were generally maintained from 6 to 16 wks of age. Growth
      related increases in cortical cross-sectional geometry and longitudinal bone
      curvature had counteracting effects on induced bone stresses and, therefore,
      maintained tibial stiffness similarly with growth. Tissue mineral density
      increased slightly from 6 to 16 wks of age, and although the effects of this
      increase on tibial stiffness were not directly measured, its role in the
      modulation of whole bone stiffness was likely minor over the age range examined.
      Thus, whole bone morphology, as characterized by longitudinal curvature, along
      with cortical geometry, plays an important role in modulating bone stiffness
      during development and should be considered when evaluating and designing in vivo
      loading studies and biophysical skeletal therapies.

PMID- 20673666
TI  - Finite element analysis of an accordion-like honeycomb scaffold for cardiac
      tissue engineering.
AB  - Optimizing the function of tissue engineered cardiac muscle is becoming more
      feasible with the development of microfabricated scaffolds amenable to
      mathematical modeling. In the current study, the elastic behavior of a recently
      developed poly(glycerol sebacate) (PGS) accordion-like honeycomb (ALH) scaffold
      [Engelmayr et al., 2008. Nature Materials 7 (12), 1003-1010] was analyzed.
      Specifically, 2D finite element (FE) models of the ALH unit cell (periodic
      boundary conditions) and tessellations (kinematic uniform boundary conditions)
      were utilized to determine a representative volume element (RVE) and to
      retrospectively predict the elastic effective stiffnesses. An RVE of 90 ALH unit
      cells (?3.18*4.03mm) was found, indicating that previous experimental uni-axial
      test samples were mechanically representative. For ALH scaffolds microfabricated
      from PGS cured 7.5h at 160 degrees C, FE predicted effective stiffnesses in the
      two orthogonal material directions (0.081+/-0.012 and 0.033+/-0.005MPa) matched
      published experimental data (0.083+/-0.004 and 0.031+/-0.002MPa) within 2.4% and
      6.4%. Of potential use as a design criterion, model predicted global strain
      amplifications were lower in ALH (0.54 and 0.34) versus rectangular honeycomb
      (1.19 and 0.74) scaffolds, appearing to be inversely correlated with previously
      measured strains-to-failure. Important in matching the anisotropic mechanical
      properties of native cardiac muscle, FE predicted ALH scaffolds with 50MUm wide
      PGS struts to be maximally anisotropic. The FE model will thus be useful in
      designing future variants of the ALH pore geometry that simultaneously provide
      proper cardiac anisotropy and reduced stiffness to enhance heart cell-mediated
      contractility.

PMID- 20673667
TI  - Are fixed limb inertial models valid for dynamic simulations of human movement?
AB  - During human movement, muscle activation and limb movement result in subtle
      changes in muscle mass distribution. Muscle mass redistribution can affect limb
      inertial properties and limb dynamics, but it is not currently known to what
      extent. The objectives of this study were to investigate: (1) how physiological
      alterations of muscle and tendon length affect limb inertial characteristics, and
      (2) how such changes affect dynamic simulations of human movement. To achieve
      these objectives, a digital model of a human leg, custom software, and Software
      for interactive musculoskeletal modeling were used to simulate mass
      redistribution of muscle-tendon structures within a limb segment during muscle
      activation and joint movement. Thigh and shank center of mass and moments of
      inertia for different muscle activation and joint configurations were determined
      and compared. Limb inertial parameters representing relaxed muscles and fully
      active muscles were input into a simulated straight-leg movement to evaluate the
      effect inertial parameter variations could have on movement simulation results.
      Muscle activation and limb movement altered limb segment center of mass and
      moments of inertia by less than 0.04 cm and 1.2%, respectively. These variations
      in limb inertial properties resulted in less than 0.01% change in maximum angular
      velocity for a simulated straight-leg hip flexion task. These data demonstrate
      that, for the digital human leg model considered, assuming static quantities for
      segment center of masses and moments of inertia in movement simulations appear
      reasonable and induce minimal errors in simulated movement dynamics.

PMID- 20673668
TI  - High strain rate response of rabbit femur bones.
AB  - Strain rate dependence of the mechanical response of hard tissues has led to a
      keen interest in their dynamic properties. The current study attempts to
      understand the high strain rate characteristics of rabbit femur bones. The
      testing was conducted using a split-Hopkinson pressure bar equipped with a high
      speed imaging system to capture the fracture patterns. The bones were also
      characterized under quasi-static compression to enable comparison with the high
      strain rate results. The quasi-static compressive moduli of the epiphyseal and
      diaphyseal regions were measured to be in the range of 2-3 and 5-7GPa,
      respectively. Under high strain rate loading conditions the modulus is observed
      to increase with strain rate and attains values as high as 15GPa for epiphyseal
      and 30GPa for diaphyseal regions of the femur. The strength at high strain rate
      was measured to be about twice the quasi-static strength value. A large number of
      small cracks initiated on the specimen surface close to the incident bar.
      Coalescence of crack branches leading to fewer large cracks resulted in specimen
      fragmentation. In comparison, the quasi-static failure was due to shear cracking.

PMID- 20673669
TI  - Anisotropic and hyperelastic identification of in vitro human arteries from full
      field optical measurements.
AB  - In this paper, we present a new approach for the bi-axial characterization of in
      vitro human arteries and we prove its feasibility on an example. The specificity
      of the approach is that it can handle heterogeneous strain and stress
      distributions in arterial segments. From the full-field experimental data
      obtained in inflation/extension tests, an inverse approach, called the virtual
      fields method (VFM), is used for deriving the material parameters of the tested
      arterial segment. The obtained results are promising and the approach can
      effectively provide relevant values for the anisotropic hyperelastic properties
      of the tested sample.

PMID- 20673670
TI  - Comparison between in vivo and theoretical bite performance: using multi-body
      modelling to predict muscle and bite forces in a reptile skull.
AB  - In biomechanical investigations, geometrically accurate computer models of
      anatomical structures can be created readily using computed-tomography scan
      images. However, representation of soft tissue structures is more challenging,
      relying on approximations to predict the muscle loading conditions that are
      essential in detailed functional analyses. Here, using a sophisticated multi-body
      computer model of a reptile skull (the rhynchocephalian Sphenodon), we assess the
      accuracy of muscle force predictions by comparing predicted bite forces against
      in vivo data. The model predicts a bite force almost three times lower than that
      measured experimentally. Peak muscle force estimates are highly sensitive to
      fibre length, muscle stress, and pennation where the angle is large, and
      variation in these parameters can generate substantial differences in predicted
      bite forces. A review of theoretical bite predictions amongst lizards reveals
      that bite forces are consistently underestimated, possibly because of high levels
      of muscle pennation in these animals. To generate realistic bites during
      theoretical analyses in Sphenodon, lizards, and related groups we suggest that
      standard muscle force calculations should be multiplied by a factor of up to
      three. We show that bite forces increase and joint forces decrease as the bite
      point shifts posteriorly within the jaw, with the most posterior bite location
      generating a bite force almost double that of the most anterior bite. Unilateral
      and bilateral bites produced similar total bite forces; however, the pressure
      exerted by the teeth is double during unilateral biting as the tooth contact area
      is reduced by half.

PMID- 20673671
TI  - Brownian dynamics simulation of the crystallization dynamics of charged colloidal
      particles.
AB  - Crystal formation process of charged colloidal particles is investigated using
      Brownian dynamics (BD) simulations. The particles are assumed to interact with
      the pair-additive repulsive Yukawa potential. The time evolution of
      crystallization process and the crystal structure during the simulation are
      characterized by means of the radial distribution functions (RDF) and mean square
      displacement (MSD). The simulations show that when the interaction is featured
      with long-range, particles can spontaneously assemble into body-centered-cubic
      (BCC) arrays at relatively low particle number density. When the interaction is
      short-ranged, with increasing the number density particles become trapped into a
      stagnant disordered configuration before the crystallization could be actualized.
      The simulations further show that as long as the trapped configurations are
      bypassed, the face-centered-cubic (FCC) structures can be achieved and are
      actually more stable than BCC structures.

PMID- 20673672
TI  - Deposition kinetics of zinc oxide nanoparticles on natural organic matter coated
      silica surfaces.
AB  - The deposition kinetics of ZnO nanoparticles on silica surfaces and surfaces that
      pre-coated with Suwannee River humic acid (SRHA) were examined over a wide range
      of environmentally relevant ionic strengths in both monovalent and divalent
      solutions by employing a quartz crystal microbalance with dissipation (QCM-D).
      Deposition efficiencies of ZnO nanoparticles on bare silica surfaces increased
      with increasing ionic strength in both NaCl and CaCl(2) solutions, which agreed
      with the trends of interaction forces between nanoparticle and silica surface and
      thus was consistent with classic Derjaguin-Landau-Verwey-Overbeek (DLVO) theory.
      The presence of divalent cation Ca(2+) in solutions greatly enhanced the
      deposition kinetics of ZnO nanoparticles on silica surfaces. Pre-coated SRHA on
      silica surfaces hindered the deposition of ZnO nanoparticles in both monovalent
      and divalent solutions, which was not consistent with classic DLVO theory. Steric
      repulsion, a non-DLVO interaction, was found to be a major mechanism controlling
      the deposition of ZnO nanoparticle on SRHA-coated silica surfaces.

PMID- 20673673
TI  - Sociodemographic, behavioral, and substance use correlates of reckless driving in
      the United States: findings from a national Sample.
AB  - This study examined the sociodemographic, behavioral, psychiatric, and substance
      use correlates of three forms of reckless driving using a nationally
      representative sample of U.S. adults. Participants were 43,093 adults from the
      National Epidemiologic Survey on Alcohol and Related Conditions (NESARC).
      Interviewers administered the Alcohol Use Disorder and Associated Disabilities
      Interview Schedule--DSM-IV version (AUDADIS-IV). This measure provides extensive
      sociodemographic data as well as diagnoses for mood, anxiety, personality, and
      substance use disorders. Reckless driving was significantly associated with male
      gender, lower levels of income, being born in the U.S., and numerous forms of
      antisocial behaviors. Fully adjusted models revealed significant effects with
      respect to substance use disorders across categories of reckless drivers with
      those having their licenses revoked or suspended being particularly more likely
      to be diagnosed with antisocial (AOR = 3.35, 95% CI = 2.54, 4.42) and paranoid
      personality disorder (AOR = 1.56, 95% CI = 1.07, 2.29). All three reckless
      driving groups were more likely to have a family history of antisocial behavior
      than non-reckless drivers. Study findings provide information from which targeted
      behavioral interventions can be applied.

PMID- 20673674
TI  - Successful treatment with rituximab and thalidomide of POEMS syndrome associated
      with Waldenstrom macroglobulinemia.
AB  - A POEMS syndrome is a rare disorder characterized by polyneuropathy,
      organomegaly, endocrinopathy, monoclonal gammopathy and skin abnormalities
      including hyperpigmentation and hypertrichosis. Here we report a 55-year-old
      female case of a POEMS syndrome associated with Waldenstrom macroglobulinemia.
      The patient had bed-bound polyneuropathy, splenomegaly, IgM-lambda type
      monoclonal (M) protein, elevated lambda-type free light chain (FLC), infiltration
      of CD20-positive lymphoplasmacytic cells in bone marrow, edema and
      hypertrichosis, and was diagnosed to have an 'atypical' POEMS syndrome associated
      with macroglobulinemia. Nerve conduction studies and a sural nerve biopsy
      confirmed a demyelination and axonal degeneration without IgM deposition on
      myelin sheathes. None of neuron-related auto-antibodies characteristic of IgM
      paraproteinemic neuropathies was detected in her serum and cerebrospinal fluid.
      Weekly administration of rituximab (375mg/m(2)) combined with thalidomide
      (50mg/day) was initiated. By eight weeks of the treatment, the ambulation
      activity of the patient was restored and her polyneuropathy completely
      disappeared as determined by clinical symptoms and electrophysiological
      examinations. This is the first case report presenting a POEMS syndrome
      associated with WM treated with rituximab and thalidomide. The further
      examinations of the present case should shed light on the pathogenesis of the
      'atypical' POEMS syndrome.

PMID- 20673675
TI  - Malnutrition at the time of diagnosis is associated with a shorter disease
      duration in ALS.
AB  - BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative
      disease. During the course of the illness, malnutrition can occur and may shorten
      survival. The aim of our study was to determine whether clinical nutritional
      parameters that are used in daily practice are associated with prognosis and
      whether they can help guide therapeutic decisions. METHODS: We retrospectively
      reviewed a cohort of ALS patients in our institution between January 2002 and
      January 2006. Clinical and demographic outcomes were compiled. To evaluate
      predictors of survival, we analyzed several clinical nutritional parameters
      available in daily practice (body mass index, weight loss exceeding 10% of
      premorbid weight at the time of diagnosis and during the course of the disease
      and the use of technical supports such as percutaneous endoscopic gastrostomy
      (PEG) and non-invasive ventilation). RESULTS: Sixty-three patients were
      retrospectively studied. Thirteen patients had weight loss exceeding 10% of
      premorbid weight at the time of diagnosis and thirty patients had weight loss
      meeting this criterion at final examination. Weight loss exceeding 10% at the
      time of diagnosis was associated with a shorter duration of disease (17+/-6months
      versus 35+/-26months; p=0.002). A linear correlation was found between mean
      disease duration and time between onset and diagnosis (p<0.0001). The subgroup of
      patients with a PEG had a longer survival time than the other subgroup of
      patients (p=0.02). CONCLUSIONS: In ALS patients, early and marked weight loss
      significantly predicts a worse prognosis. The percentage of premorbid weight loss
      is a suitable and useful measure that can be used in daily practice to identify
      patients with a poor prognosis.

PMID- 20673676
TI  - Phase distribution of hydrocarbons in the water column after a pelagic deep ocean
      oil spill.
AB  - Spills from wrecks are a potential major source of pollution in the deep ocean.
      However, not much is known about the fate of a spill at several kilometers depth,
      beyond the oceans continental shelves. Here, we report the phase distribution of
      hydrocarbons released from the wrecks of the Prestige tanker, several years after
      it sank in November 2002 to depths between 3500 and 3800 m. The released oil
      reached the surface waters above the wrecks without any signs of weathering and
      leaving an homogenous signature throughout the water column. At depths of several
      kilometers below the sea surface, the occurrence and spread of the deep sea oil
      spill could be evaluated better by quantifying and characterizing the dissolved
      hydrocarbon signature, rather than just the investigation of hydrocarbons in the
      suspended particulate matter.

PMID- 20673678
TI  - [Usefulness of brain natriuretic peptide levels, as compared with usual clinical
      control, for the treatment monitoring of patients with heart failure].
AB  - BACKGROUND AND OBJECTIVES: Chronic heart failure continues to have a poor
      prognosis, in spite of advances made in its therapy. It is uncertain whether
      symptom-guided therapy optimization is the most effective strategy in this
      setting. The aim of our study was to evaluate the usefulness of a brain
      natriuretic peptide (BNP)-guided therapy for the treatment of patients with heart
      failure. PATIENTS AND METHODS: We carried out a prospective and randomized study
      including 60 patients consecutively discharged with the diagnosis of heart
      failure NYHA class III or IV in one cardiology department of a Spanish hospital;
      30 patients were randomly assigned to a symptom-guided therapy group based on the
      clinical Framingham score, and 30 to a BNP-guided therapy group. Therapy was
      adjusted to obtain a clinical score <2 in the symptom-guided group and BNP levels
      <100pg/ml in the BNP-guided group. Follow up was 16+/-4 months. RESULTS: BNP
      guided group had lower BNP levels during follow up than had symptom-guided group:
      14(20)pg/ml versus 111+/-71pg/ml at 18 months, p=0.029. Clinical score was
      similar in both groups: 0.42(0.33) versus 0.39(0.63) at 18 months. Probability of
      survival (86% in both groups) and probability of being free of readmissions for
      heart failure (68 versus 66%) at 18 months were similar in both groups.
      CONCLUSIONS: In our experience, in patients with heart failure, BNP-guided
      therapy did not improve clinical outcomes compared with symptom-guided therapy.

PMID- 20673677
TI  - [Evaluation of the influenza a H1N1 vaccination in Castilla and Leon regions,
      Spain].
AB  - BACKGROUND AND OBJECTIVES: The recent approval of influenza A H1N1 monovalent
      vaccine has attracted considerable public health interest. The aim of this paper
      is to assess the development of vaccination campaign in Castilla y Leon. MATERIAL
      AND METHOD: We have performed a descriptive analysis of the number of vaccines
      given in Castilla y Leon from November 16, 2009 to January 17, 2010, inside the
      designed campaign for that purpose. RESULTS: The total number of vaccines
      administered has been 116,243, 86,810 of which were from Focetria((r)) which were
      administered to 3286 children under 18 years; 28,439 were from Pandemrix((r)) and
      994 from Panenza((r)). The estimated vaccination coverage for all of the target
      groups has reached a percentage of 26.3% while the coverage achieved in pregnant
      women has been 4.7%. Of all the vaccines administered during this period, 82.2%
      were applied in the first month of the vaccination campaign. CONCLUSION: The
      introduction of pandemic vaccine in target groups of Castilla y Leon has been
      lower than expected, with a mismatch between the different health areas.

PMID- 20673679
TI  - [Prognostic value of NT-proBNP in chronic pulmonary disease exacerbation].
AB  - BACKGROUND AND OBJECTIVE: Brain natriuretic peptide (BNP) is produced and
      released mainly from ventricles. BNP has been shown to be useful in diagnosis and
      prognosis in heart failure and some pulmonary conditions. The aim of this study
      is to analyse whether NT-proBNP has a prognostic value in chronic pulmonary
      patients without overt heart failure. PATIENT AND METHOD: We conducted an
      observational and prospective study. We included 192 patients admitted to the
      Internal Medicine Departments of Hospital Clinico "Lozano Blesa" (Zaragoza,
      Spain) and "Virgen de la Luz" (Cuenca, Spain) with acute exacerbation of
      pulmonary disease. Blood samples were taken to determine NT-proBNP
      concentrations. All patients were followed for 6 months after admission. RESULTS:
      6,3% of patients died, 22,9% were prescribed with home oxygen-therapy, 18,2%
      received a diuretic prescription and 21,9% were re-admitted at least once during
      the follow-up period. Mean NT-proBNP was 1180pg/ml. A concentration above
      500pg/ml and 350pg/ml of NT-proBNP was useful to predict mortality and diuretic
      prescription respectively. CONCLUSIONS: Among patients with acute exacerbations
      of chronic pulmonary disease, NT-proBNP could be a prognostic factor to identify
      those at risk of death or worst clinical development.

PMID- 20673680
TI  - [Predictive factors of ESBL versus non-ESBL Escherichia coli bacteraemia and
      influence of resistance on the mortality of the patients].
AB  - BACKGROUND AND OBJECTIVES: To analyze predictor factors of extended-spectrum
      betalactamasa (ESBL)-producing E. coli and its repercussion in mortality.
      PATIENTS AND METHODS: Observational and comparative study of a cohort of non
      paediatric admitted patients with E. coli bacteraemia (EB). RESULTS: 153 EB (22%
      ESBL-producing strains). Risk factors associated with ESBLB: previous antibiotic
      treatment (OR 2.61; 95% CI 1.1-6.19), severity Winston score <=2 (OR 9.83, 95% CI
      3.42-28.26) and health-related acquired infection (OR 5.35; 95% CI 1.57-18.27).
      Related mortality rate was 21%, being independent risk factors: cancer (OR 4.02;
      95% CI 1.08-14.82), high severity of underlying disease (McCabe) (OR 7.69; 95% CI
      1.96-30.09) and critical severity of illness at onset (Winston) (OR 48.89; 95% CI
      11.58-206.97). Inappropriate empirical therapy was more frequent in EBSL
      producing group (67%, p<0.05). CONCLUSIONS: Previous antibiotic treatment,
      severity Winston score <=2 and health-related acquisition are factors associated
      to ESBL EB. EBSL-producing strains or inadequate treatment were not associated to
      higher mortality. Factors statistically associated to mortality were cancer,
      severity of underlying diseases and critical severity of illness at onset.

PMID- 20673681
TI  - [Opioid rotation: a therapeutic choice in the management of refractory cancer
      pain].

PMID- 20673682
TI  - Plasma Epstein-Barr viral load measurement as a diagnostic marker of lymphoma in
      HIV-infected patients.
AB  - BACKGROUND AND OBJECTIVES: To assess the use of the Epstein-Barr virus (EBV)
      viral load as a marker for lymphoma diagnosis in HIV-infected patients. We also
      aimed to identify the relationship between EBV viral load in plasma and the
      presence of EBV in lymphoma cells. PATIENTS AND METHODS: Retrospective
      observational study of two HIV-infected populations: one of patients diagnosed
      with lymphoma and a control group. Thirty-nine patients with AIDS-related
      lymphoma (ARL) (32 non-Hodgkin's and 7 Hodgkin's lymphomas) and 134 HIV-positive
      individuals without neoplasia or opportunistic infections were studied. Blood
      samples were collected before lymphoma treatment in ARL patients. EBV viral load
      was measured in plasma by real-time quantitative PCR and the presence of EBV-EBER
      mRNA in lymphoma tumor was investigated by in situ hybridization. RESULTS:
      Patients with ARL had higher EBV viral loads than those without lymphoma:
      24,180.5 (+/-73,387.6)copies/mL versus 2.6 (+/-21.6)copies/mL (p<0.001). HIV
      infected patients without lymphoma had negative or very low EBV load values.
      Among ARL patients, no correlation was found between EBV viral loads and CD4+
      lymphocyte counts or between EBV and HIV RNA loads, or any other clinical or
      biological parameter. Cases with an EBV-EBER-positive lymphoma had higher EBV
      viral loads than those with EBER-negative tumors. CONCLUSIONS: EBV viral load is
      a useful marker of lymphoma in HIV-infected patients, and may be a useful tool
      for early diagnosis and treatment.

PMID- 20673683
TI  - Chlorotoxin bound magnetic nanovector tailored for cancer cell targeting,
      imaging, and siRNA delivery.
AB  - Ribonucleic acid interference (RNAi) is a powerful molecular tool that has
      potential to revolutionize the treatment of cancer. One major challenge of
      applying this technology for clinical application is the lack of site-specific
      carriers that can effectively deliver short interfering RNA (siRNA) to cancer
      cells. Here we report the development and assessment of a cancer-cell specific
      magnetic nanovector construct for efficient siRNA delivery and non-invasive
      monitoring through magnetic resonance imaging (MRI). The base of the nanovector
      construct is comprised of a superparamagnetic iron oxide nanoparticle core coated
      with polyethylene glycol (PEG)-grafted chitosan, and polyethylenimine (PEI). The
      construct was then further functionalized with siRNA and a tumor-targeting
      peptide, chlorotoxin (CTX), to improve tumor specificity and potency. Flow
      cytometry, quantitative RT-PCR, and fluorescence microscopy analyses confirmed
      receptor-mediated cellular internalization of nanovectors and enhanced gene
      knockdown through targeted siRNA delivery. The ability of this nanovector
      construct to generate specific contrast enhancement of glioblastoma cells was
      demonstrated through MR imaging. These findings suggest that this CTX enabled
      nanoparticle carrier may be well suited for delivery of RNAi therapeutics to
      brain cancer cells.

PMID- 20673684
TI  - Core-crosslinked polymeric micelles with controlled release of covalently
      entrapped doxorubicin.
AB  - Doxorubicin (DOX) is clinically applied in cancer therapy, but its use is
      associated with dose limiting severe side effects. Core-crosslinked biodegradable
      polymeric micelles composed of poly(ethylene glycol)-b-poly[N-(2-hydroxypropyl)
      methacrylamide-lactate] (mPEG-b-p(HPMAm-Lac(n))) diblock copolymers have shown
      prolonged circulation in the blood stream upon intravenous administration and
      enhanced tumor accumulation through the enhanced permeation and retention (EPR)
      effect. However a (physically) entrapped anticancer drug (paclitaxel) was
      previously shown to be rapidly eliminated from the circulation, likely because
      the drug was insufficiently retained in the micelles. To fully exploit the EPR
      effect for drug targeting, a DOX methacrylamide derivative (DOX-MA) was
      covalently incorporated into the micellar core by free radical polymerization.
      The structure of the doxorubicin derivative is susceptible to pH-sensitive
      hydrolysis, enabling controlled release of the drug in acidic conditions (in
      either the intratumoral environment and/or the endosomal vesicles). 30-40% w/w of
      the added drug was covalently entrapped, and the micelles with covalently
      entrapped DOX had an average diameter of 80 nm. The entire drug payload was
      released within 24 h incubation at pH 5 and 37 degrees C, whereas only around 5%
      release was observed at pH 7.4. DOX micelles showed higher cytotoxicity in B16F10
      and OVCAR-3 cells compared to DOX-MA, likely due to cellular uptake of the
      micelles via endocytosis and intracellular drug release in the acidic organelles.
      The micelles showed better anti-tumor activity than free DOX in mice bearing
      B16F10 melanoma carcinoma. The results presented in this paper show that mPEG-b
      p(HPMAm-Lac(n)) polymeric micelles with covalently entrapped doxorubicin is a
      system highly promising for the targeted delivery of cytostatic agents.

PMID- 20673685
TI  - Transferrin-conjugated nanoparticles of poly(lactide)-D-alpha-tocopheryl
      polyethylene glycol succinate diblock copolymer for targeted drug delivery across
      the blood-brain barrier.
AB  - We developed in this research a nanoparticle system for targeted drug delivery
      across the blood-brain barrier (BBB), which consists of the transferrin (Tf)
      conjugated nanoparticles of poly(lactide)-D-alpha-Tocopheryl polyethylene glycol
      succinate (PLA-TPGS) diblock copolymer. The NPs were prepared by the
      nanoprecipitation method and characterized for their various physicochemical and
      pharmaceutical properties. Cellular uptake and cytotoxicity of the Tf-conjugated
      PLA-TPGS NPs formulation of coumarin 6 as a model imaging agent or Docetaxel as a
      model drug were investigated in close comparison with those for the PLGA NPs
      formulation, the bare PLA-TPGS NPs formulation as well as with the clinical
      Taxotere. The Tf-conjugated PLA-TPGS NPs formulation demonstrated great
      advantages over the other two NPs formulations and the original
      imaging/therapeutic agents. IC50 data showed that the Tf-conjugated PLA-TPGS NPs
      formulation of Docetaxel could be 23.4%, 16.9% and 229% more efficient than the
      PLGA NPs, the PLA-TPGS NPs formulations and Taxotere after 24 h treatment,
      respectively. Moreover, our preliminary ex vivo biodistribution investigation
      demonstrated that although not as satisfactory, the Tf-conjugated PLA-TPGS NPs
      formulation could be able to deliver imaging/therapeutic agents across the BBB.

PMID- 20673686
TI  - Mercury hair concentrations and dietary exposure among Inuit preschool children
      in Nunavut, Canada.
AB  - There is concern that the traditional diet is a source of mercury exposure among
      Inuit in the Canadian Arctic. Mercury exposure in utero and in early childhood
      presents a risk to neurodevelopment. The objectives of the present study were to
      assess the dietary mercury exposure from traditional food among Inuit children 3
      to 5 years of age in Nunavut, and evaluate the association between estimated
      dietary mercury intake and body burden. A cross-sectional Nunavut Inuit Child
      Health Survey was conducted in 2007 and 2008 which included assessment of dietary
      habits and children's hair mercury (Hg) levels. Further, an Inuit Adult Health
      Survey was conducted in the same years which included assessment of dietary
      habits and whole blood mercury concentrations. Traditional food samples were
      collected during this study and previously from the Canadian Arctic. Daily
      mercury intake from traditional food was calculated. Body mercury burden was
      determined using the hair mercury concentration. The geometric mean of children's
      hair Hg was 0.66 MUg/g and varied by region. Nearly 25% of children had hair Hg
      concentrations equal to or higher than 2 MUg/g (WHO reference level). There was a
      significant correlation between mercury levels in children's hair and that of the
      adults in the same household. For children, beluga muktuk, narwhal muktuk, ringed
      seal liver, fish, caribou meat and ringed seal meat were the major dietary
      sources of mercury. These food items together accounted for over 95% of total
      daily dietary mercury intake. A positive linear regression relationship between
      children's hair mercury levels and estimated dietary mercury intake was observed.
      Estimated intake in Baffin decreased by 30% compared to 20 years ago. Some
      traditional food items were significant sources of mercury to Inuit children in
      Nunavut. Although a reduction in the consumption of these diet items may be a way
      to reduce mercury intake, the nutritional, social and cultural benefits of
      traditional food and countervailing risks must be taken into account in risk
      mitigation.

PMID- 20673687
TI  - Dechlorane plus in multimedia in northeastern Chinese urban region.
AB  - Dechlorane plus (DP) was quantified by gas chromatography/mass spectrometry
      (GC/MS) in soil and ambient air (collected from Harbin City, a typical
      northeastern Chinese urban region), water and sediment samples (collected in the
      segment within Harbin of Songhua River, located in northeast of China). The
      average concentrations of DP in sediment and soil samples were 123.6 pg g-1 dry
      weight (dw), and 11.3 pg g-1 dw, respectively. However, the concentration of DP
      in water was below the method detection limit (MDL). The inter-media comparison
      between water and sediment suggested that the sediment may be a receptor for DP.
      For air samples, two methods were used for collecting air in order to compare,
      active air sampling (AAS) and passive air sampling (PAS). The average
      concentrations of DP were 0.4 pg m-3 and 6.9 pg m-3 for AAS and PAS samples,
      respectively. Discrepancies of deployment period and different calculated method
      for DP concentration may help to explain the remarkable difference between PAS
      and AAS. Overall, DP in all matrices in Harbin City showed lower concentrations
      than that in the Great Lakes region. The anti-DP isomer was consistently greater
      than that of the syn-DP isomer in all matrices. The average fractional abundance
      of the syn-DP isomer (f(syn)) was smaller than the technical DP composition
      (f(syn)=0.35) according to other studies in the Great Lakes region. As we know,
      this study is the first attempt to comprehensively study DP concentrations in
      four different matrices (water, ambient air, sediment and soil) in China.

PMID- 20673688
TI  - Evaluation of in vitro cytotoxicity and hepatotoxicity of platinum(II) and
      palladium(II) oxalato complexes with adenine derivatives as carrier ligands.
AB  - In vitro antitumour activity of the [Pt(ox)(L(n))(2)] (1-7) and [Pd(ox)(L(n))(2)]
      (8-14) oxalato (ox) complexes involving N6-benzyl-9-isopropyladenine-based N
      donor carrier ligands (L(n)) against ovarian carcinoma (A2780), cisplatin
      resistant ovarian carcinoma (A2780cis), malignant melanoma (G-361), lung
      carcinoma (A549), cervix epitheloid carcinoma (HeLa), breast adenocarcinoma
      (MCF7) and osteosarcoma (HOS) human cancer cell lines was studied. Some of the
      tested complexes were even several times more cytotoxic as compared with
      cisplatin employed as a positive control. The improved cytotoxic effect was
      demonstrated for the platinum(II) complexes 3 (IC(50)=3.2+/-1.0 microM and 3.2+/
      0.6 microM) and 5 (IC(50)=4.0+/-1.0 microM and 4.1+/-1.4 microM) against A2780
      and A2780cis, as compared with 11.5+/-1.6 microM, and 30.3+/-6.1 microM
      determined for cisplatin, respectively. The significant in vitro cytotoxicity
      against MCF7 (IC(50)=8.2+/-3.8 microM for 12) and A2780 (IC(50)=5.4+/-1.2 microM
      for 14) was evaluated for the palladium(II) oxalato complexes, which again
      exceeded cisplatin, whose IC(50) equalled 19.6+/-4.3 microM against the MCF7
      cells. Selected complexes were also screened for their in vitro cytotoxic effect
      in primary cultures of human hepatocytes and they were found to be non
      hepatotoxic.

PMID- 20673689
TI  - Physical radiotherapy treatment planning based on functional PET/CT data.
AB  - Positron emission tomography (PET) provides molecular information about the tumor
      microenvironment in addition to anatomical imaging. Hence, it seems to be highly
      beneficial to integrate PET data into radiotherapy (RT) treatment planning.
      Functional PET images can be used in RT planning following different strategies,
      with different orders of complexity. In a first instance, PET imaging data can be
      used for better target volume delineation. A second strategy, dose painting by
      contours (DPBC), consists of creating an additional PET-based target volume which
      will then be treated with a higher dose level. In contrast, dose painting by
      numbers (DPBN) aims for a locally varying dose prescription according to the
      variation of the PET signal. For both dose painting approaches, isotoxicity
      planning strategies should be applied in order not to compromise organs at risk
      compared to conventional modern RT treatment. In terms of physical dose painting
      treatment planning, several factors that may introduce limitations and
      uncertainties are of major importance. These are the PET voxel size,
      uncertainties due to image acquisition and reconstruction, a reproducible image
      registration, inherent biological uncertainties due to biological and chemical
      tracer characteristics, accurate dose calculation algorithms and radiation
      delivery techniques able to apply highly modulated dose distributions. Further
      research is necessary in order to investigate these factors and their influence
      on dose painting treatment planning and delivery thoroughly. To date, dose
      painting remains a theoretical concept which needs further validation.
      Nevertheless, molecular imaging has the potential to significantly improve target
      volume delineation and might also serve as a basis for treatment alteration in
      the future.

PMID- 20673690
TI  - Radiation exposure of the heart, lung and skin by radiation therapy for breast
      cancer: a dosimetric comparison between partial breast irradiation using
      multicatheter brachytherapy and whole breast teletherapy.
AB  - BACKGROUND AND PURPOSE: Accelerated partial breast irradiation by means of
      multicatheter brachytherapy shows great promise in the modern treatment of early
      breast cancer combining high efficacy in preventing tumour recurrence with low
      levels of toxicity. The present work attempts a dosimetric comparison between
      this treatment modality and conventional whole breast external beam radiotherapy
      by looking at differences in risk organ exposure to radiation. PATIENTS AND
      METHODS: The planning CT data sets of 16 consecutive patients with left-sided
      breast cancer who received external beam radiotherapy to the whole breast
      followed by a boost to the tumour bed using multicatheter interstitial
      brachytherapy after breast conserving surgery were used to create two independent
      physical treatment plans - one for an external radiotherapy, one for sole partial
      breast brachytherapy in each case assuming a total reference dose of 50Gy for
      each patient. Dose-volume parameters D(0.1cc), D(0.5cc), D(1cc,)D(2cc),
      D(5cc,)D(10cc), D(25cc), D(50cc), V(100), V(90), V(50), V(10), V(5) for the
      ipsilateral lung, the heart and the adjacent skin were calculated and compared
      between the two treatment modalities. RESULTS: All organs at risk showed a
      substantially lower radiation exposure in the brachytherapy plan. This was most
      pronounced for the heart with values differing by a factor of four. Although
      somewhat less marked this was also true for the ipsilateral lung and the adjacent
      skin with exposure ratios of three and two, respectively. CONCLUSIONS: With the
      use of multicatheter interstitial brachytherapy substantial reductions in the
      radiation exposure of risk organs can be achieved in comparison to whole breast
      external beam radiotherapy. These are likely to translate into profound clinical
      benefits.

PMID- 20673691
TI  - [ILCOR 2010 Conference: the process to new CPR guidelines].

PMID- 20673692
TI  - [Image fusion of gated-SPECT and CT angiography in coronary artery disease.
      Importance of anatomic-functional correlation].
AB  - A 77-year old patient was admitted for acute coronary syndrome without ST
      elevation. His risk was stratified using the myocardial perfusion gated SPECT,
      mild inferior ischemia being observed. Thus, medical therapy was optimized and
      the patient was discharged. He continued with exertional dyspnea so a coronary CT
      angiography was performed. It revealed severe lesions in the proximal RCA. SPECT
      CT fusion images correlated the myocardial perfusion defect with a posterior
      descending artery from the RCA, in a co-dominant coronary area. Subsequently,
      cardiac catheterism was indicated for his treatment. The current use of image
      fusion studies is limited to patients in whom it is difficult to attribute a
      perfusion defect to a specific coronary artery. In our patient, the fusion images
      helped to distinguish between the RCA and the circumflex artery as the culprit
      artery of ischemia.

PMID- 20673693
TI  - Using the transbuccal cannula/drill sleeve for soft tissue protection during the
      transoral approach.

PMID- 20673694
TI  - Transconjunctival incision for total maxillectomy--an alternative for subciliary
      incision.
AB  - A subciliary incision may be associated with various complications of the lower
      eyelid when it is used during a total maxillectomy. The use of the
      transconjunctival incision instead is an alternative in suitable patients. The
      records of 17 patients were reviewed in whom a transconjunctival incision was
      used during total maxillectomy. These included 13 in whom the Weber-Ferguson
      incision was used, and 4 who had a sublabial incision. There was mild
      conjunctival oedema in all the cases during the immediate postoperative period
      but it did not last for more than two days. Four patients had mild to moderate
      oedema of the lid that resolved within two days. One had mild ectropion with
      transient epiphora, which was caused by early removal of the medial canthal
      sutures. We found the approach to be cosmetically acceptable as it avoids a scar
      in the subciliary region. The transconjunctival incision can be used in place of
      the subciliary incision for lateral exposure during total maxillectomy. There are
      few complications associated with the lower lid, and it has good cosmetic
      results; if it is combined with a sublabial incision in suitable patients, the
      maxillectomy is virtually scar-free.

PMID- 20673695
TI  - The association between reduced GFR and hearing loss: a cross-sectional
      population-based study.
AB  - BACKGROUND: Chronic kidney disease (CKD) has long been associated with hearing
      loss in certain syndromes. Reported evidence to date has come from only small
      observational studies. We present the first community-based study to show an
      association between nonsyndromal CKD and hearing loss. STUDY DESIGN: Cross
      sectional population-based study to examine the relationship between CKD and age
      related hearing loss. SETTING & PARTICIPANTS: The Blue Mountains Hearing Study is
      a survey of age-related hearing loss conducted in 1997-2004; a total of 2,564
      participants had audiometric testing and complete renal data. PREDICTOR OR
      FACTOR: Moderate CKD, defined as estimated glomerular filtration rate (eGFR) <60
      mL/min/1.73 m(2). OUTCOMES: Bilateral hearing loss, defined as average pure-tone
      threshold >25 dB for measurements at frequencies of 0.5, 1.0, 2.0, and 4.0 kHz.
      MEASUREMENTS: Baseline biochemistry tests, including serum creatinine, were
      performed. Pure-tone audiometry was performed in sound-treated booths. RESULTS:
      Moderate CKD was present in 513 of 2,564 participants. Of persons with moderate
      CKD, 279 (54.4%) had measured hearing loss compared with 581 (28.3%) with eGFR
      >=60 mL/min/1.73 m(2). Moderate CKD was independently associated with hearing
      loss (OR, 1.43; 95% CI, 1.10-1.84; P = 0.006) after adjusting for age; sex; noise
      exposure; education; diabetes, hypertension, and stroke histories; and smoking.
      Participants with eGFR <45 mL/min/1.73 m(2) had the highest prevalence of hearing
      loss (73%) compared with those with eGFR >=90 mL/min/1.73 m(2) (19%; multivariate
      adjusted OR, 2.4 [95% CI, 1.3-4.5]). Analyses were repeated after excluding
      participants reporting furosemide use (a known ototoxic agent); the association
      between moderate CKD and hearing loss remained significant (multivariate adjusted
      OR, 1.40 [95% CI, 1.08-1.83]; P = 0.01). LIMITATIONS: The present study is not
      longitudinal and does not permit causal inference from the observed associations.
      CONCLUSIONS: Moderate CKD per se was associated independently with hearing loss.
      Recognizing this link could lead to earlier hearing assessment with appropriate
      interventions to preserve the hearing of patients with CKD.

PMID- 20673696
TI  - [Combined pulmonary fibrosis and emphysema].
AB  - The combination of pulmonary fibrosis and emphysema (CPFE) is a recently defined
      syndrome, in which an upper lobe emphysema and lower lobe fibrosis coexist in a
      single patient. These patients have a characteristic lung function profile, with
      dynamic and static lung volumes apparently normal or minimally altered,
      contrasting with a significant reduction of carbon monoxide transfer (DLco) and
      exercise hypoxemia. Pulmonary hypertension is highly prevalent and is the
      principal negative prognostic factor for this condition. High resolution computed
      axial tomography (HRCT) is the main tool to confirm the diagnosis. Cigarette
      smoking has been proposed as the main factor in its etiology; however, neither
      pathogenic mechanisms nor the sequence of events involved in this syndrome has
      been clarified yet. Experimental studies in animal models are providing
      information on the involvement of some inflammatory mediators in the
      pathogenesis. There is currently no consensus on the therapeutic approach to be
      followed in these patients, since those published to date on this subject are
      limited to well-characterised series of cases. Therefore, it is a pathology with
      many unknowns yet to be resolved and highly likely to be underdiagnosed, unless
      its functional clinical characteristics are taken into account.

PMID- 20673697
TI  - Targeting apoptosis pathways by natural compounds in cancer: marine compounds as
      lead structures and chemical tools for cancer therapy.
AB  - Natural compounds derived from marine organisms have shown a wide variety of anti
      tumor effects and a lot of attention has been drawn to further development of the
      isolated compounds. A vast quantity of individual chemical structures from
      different organisms has shown a variety of apoptosis inducing mechanisms in a
      variety of tumor cells. The bis-steroidal cephalostatin 1 for example, induces
      apoptosis via activation of caspases whereas the polyketide discodermolide
      inhibits cell growth by binding to and stabilizing microtubule and salisporamide
      A, the product of an actinobacterial strain, is an inhibitor of the proteasome.
      This great variety of mechanisms of action can help to overcome the multitude of
      resistances exhibited by different tumor specimens. Products from marine
      organisms and their synthetic derivates are therefore an important source for new
      therapeutics for single agent or combined therapy with other chemotherapeutics to
      support the struggle against cancer.

PMID- 20673698
TI  - Combinations of mTORC1 inhibitor RAD001 with gemcitabine and paclitaxel for
      treating non-Hodgkin lymphoma.
AB  - Single-agent mammalian target of rapamycin complex 1 (mTORC1) inhibitors have
      recently been reported as effective salvage treatment in non-Hodgkin lymphoma
      (NHL). The combined effect of mTORC1 inhibitor, RAD001, with chemotherapeutic
      agents used for relapsed or refractory NHL was examined. Synergistic interactions
      were observed for RAD001 plus gemcitabine or paclitaxel in six NHL cell lines;
      enhanced gemcitabine- and paclitaxel-induced caspase-dependent apoptosis
      associated with down-regulation of mTOR signaling was detected. Synergistic
      interactions were also observed with RAD001 plus gemcitabine and paclitaxel. In
      conclusion, synergistic cytotoxicity was observed with RAD001 plus gemcitabine
      and paclitaxel in NHL cells. Combination therapy with these three drugs should be
      examined in patients with refractory or relapsed NHL.

PMID- 20673701
TI  - Cancer of unknown primary patients with midline nodal distribution: midway
      between poor and favourable prognosis?
AB  - BACKGROUND: Midline nodal cancer of unknown primary (CUP) has varying definitions
      and an unclear natural history compared to that of extragonadal germ cell cancer
      (EGCC) and neuroendocrine tumors. METHODS: We systematically reviewed all
      published series of patients with midline nodal CUP using three distinct
      definitions and presented our own retrospective cohort. RESULTS: Sixty four fit
      patients (median age 64) with poorly differentiated carcinoma or adenocarcinoma
      in midline nodal areas were treated from 1998 to 2008 at our center. Only two
      patients had elevated serum germ cell markers. Forty-eight percentage of patients
      responded to platinum-based chemotherapy (CR 11%). The median survival was 12
      months (2-year survival 18%). Good PS (Hazard Ratio HR 0.287, p=0.058) and
      administration of platinum (HR 0.340, p=0.08) predicted for more favourable
      outcome. A subgroup of 15 male patients selected with stricter criteria had a CR
      rate of 33% and median survival of 18 months (2-year survival 24%). We identified
      10 series of midline nodal CUP patients defined with discordant criteria. Despite
      high response rates (35-65%) to platinum chemotherapy, the median survival
      clustered around 12 months. Predictive factors for superior survival were low
      tumor bulk, patient fitness, female gender, carcinomatous histology, and absence
      of visceral metastases. There were differences between midline nodal CUP patients
      and EGCC as well as neuroendocrine tumors (age, tumor markers, response to
      therapy, long-term survival). CONCLUSIONS: Midline nodal CUP patients are poorly
      defined, fare less well than EGCC or neuroendocrine cancer and probably
      constitute a heterogeneous entity with a minority harbouring atypical germ cell
      cancer.

PMID- 20673699
TI  - Inhibition of cyclooxygenase-2-dependent survivin mediates decursin-induced
      apoptosis in human KBM-5 myeloid leukemia cells.
AB  - We demonstrate that decursin induces apoptosis via regulation of cyclooxygenase-2
      (COX-2) and survivin in leukemic KBM-5 cells. By activating an apoptotic
      machinery, decursin is cytotoxic to KBM-5 cells. In this apoptotic process,
      decursin can activate caspase family members and triggers PARP cleavage. At the
      same time, the expression of COX-2 and survivin in the cells is downregulated.
      Furthermore, decursin is in synergy with COX-2 inhibitor, celecoxib or NS398 for
      the induction of apoptosis. Overall, these results suggest that decursin, via
      inhibiting COX-2 and survivin, sensitizes human leukemia cells to apoptosis and
      is a potential chemotherapeutic agent to treat this disease.

PMID- 20673702
TI  - Upregulation of N-acetylaspartic acid resulting nitric oxide toxicity induces
      aspartoacylase mutations and protein interaction to cause pathophysiology seen in
      Canavan disease.
AB  - Aspartoacylase (ASPA) converts N-acetylaspartic acid into aspartate and acetate.
      In Canavan disease (CD), N-acetylaspartic acid (NAA) is found to be increased and
      over 65 mutations including IVS4+1 G -> T, deletion of introns and exons have
      been reported in the ASPA gene. These changes lead to severe form or mild form of
      CD. The present study was aimed to understand mechanism in the cause of mutations
      in ASPA and pathophysiology seen in patients with CD. We have reported that
      elevated levels of NAA induce inducible nitric oxide (iNOS) to produce nitric
      oxide toxicity in CD. Nitric oxide toxicity has been shown to induce several
      mutations including base change G -> T and deletion and enhances protein
      interaction in several genes. Therefore we hypothesize that upregulation of NAA
      stimulates NOS and the resulting nitric oxide toxicity induces ASPA mutations and
      protein interaction to result pathophysiological abnormalities seen in patients
      with CD.

PMID- 20673703
TI  - Efficacy of photodynamic therapy in cutaneous leishmaniasis: a "hidden" local
      heat effect?

PMID- 20673704
TI  - Low-dose X-ray irradiation promotes fracture healing through up-regulation of
      vascular endothelial growth factor.
AB  - Compared with high and medium dose irradiation, low-dose irradiation (LDI)
      revealed different yet healing promotion effects, such as hormesis and adaptive
      response. A recent milestone work by Zhou demonstrated that LDI at 1 Gy promoted
      callus formation and mineralization in a rat model, yet without being able to
      address the underlying mechanism. It is well known that vascular endothelial
      growth factor (VEGF) is a key cytokine that regulates angiogenesis, especially
      important found in the process of fracture healing to interplay with other
      molecules. Furthermore, recent studies revealed that tissue repair might be
      enhanced by LDI through up-regulation of the level of VEGF. In view of this
      general phenomenon, we propose the following hypothesis that low-dose X-ray
      irradiation at <= 1 Gy promotes fracture healing through up-regulation of VEGF.

PMID- 20673705
TI  - Carcass characteristics of Criollo Cordobes kid goats under an extensive
      management system: effects of gender and liveweight at slaughter.
AB  - Thirty males and thirty females suckling Criollo Cordobes kid goats of
      approximately 60 to 90 days old were used in this study. Kids were slaughtered at
      <9.5 kg, >9.5<11 kg and >11 kg of empty body weight. The carcasses showed a
      medium conformation index. The meat and fat colour, and internal subcutaneous
      fatness were mainly scored as either pink, cream, slight and low-medium,
      respectively. The shoulder comprised 66-67% muscle, 24-27% bone and 4-6% fat. The
      slaughter weight had significant effects on the following characteristics:
      dressing yield, carcass measures and indices, subcutaneous fatness, meat colour,
      and muscle/fat ratio. The effect of gender was smaller: the female kids presented
      the highest fatness values for all parameters studied. Also, these animals
      displayed the lowest percentage of joints of extra class. The meat of female kids
      contained significantly less muscle and bone and a higher proportion of fat than
      that of male kids. The allometric analysis displays an early growth in the
      carcass measures and indices, fifth quarter, joints and bone proportion of
      shoulder. Internal and dissectible fats show a late growth. Principal component
      (PC) analysis was performed to study the relationship between carcass quality
      variables. The six first PC's explained about 85% of the total variability. The
      weight and yield of the carcasses were more effective to define the first PC. The
      projection of the carcass quality data in the first two PC's allowed
      distinguishing between carcass weight and carcass conformation groups, but not
      between gender and fatness.

PMID- 20673706
TI  - Haralampos M. Moutsopoulos: a lifetime in autoimmunity.
AB  - Three years ago, the Journal of Autoimmunity and Autoimmunity Reviews launched a
      series of special issues devoted to the contributions of outstanding scholars in
      autoimmunology. The special issues are devoted not only to recognize
      achievements, but also to include a series of dedicated papers that reflect the
      scholar's work, but also are cutting-edge research and reviews in immunology.
      This special issue is devoted to Haralampos M. Moutsopoulos of the National
      University of Athens. His contributions to patient care, teaching, and original
      research are legion. The papers that are included reflect not only a wide range
      of scholarship in autoimmunology, but importantly are written by his colleagues
      and friends, and by former students. They encompass original scholarship in
      Sjogren's syndrome, but also in a number of effector pathways in both adult and
      pediatric autoimmunology.

PMID- 20673707
TI  - Visual observation of selective elution of components from skin-mimetic lipid
      membrane.
AB  - Selective elution of components was visually observed on a mixture of lipids
      (ceramide III, palmitic acid, and cholesterol) as a mimicry of stratum corneum
      (SC) which was melted and sandwiched between glass plates. The lipid membrane was
      exposed to an aqueous solution of sodium dodecyl sulphate (SDS) and observed by
      an optical microscope. The contact of the lipid membrane with a SDS solution
      caused the elution of the lipid component as "myelin-form", and the lipid
      membrane changed to a sponge structure. An infrared absorption spectroscopic
      study revealed that the SDS penetrated into the lipid mixture, and the fraction
      of ceramide in the sponge phase became higher than that in the lipid membrane
      before SDS treatment. The selective elution behaviour was confirmed by observing
      the behaviour of each component in lipid membrane by means of a fluorescence
      staining method: The cholesterol was eluted with producing visual myelin-form on
      the contact with a SDS solution, and the following elution of palmitic acid
      occurred without myelin-form, while the ceramide III resisted the exposure to the
      SDS solution. These results are valid to elucidate the influence of surfactants
      on SC.

PMID- 20673708
TI  - A review of the clinical evidence for intensity-modulated radiotherapy.
AB  - AIMS: Intensity-modulated radiotherapy (IMRT) is a development of three
      dimensional conformal radiotherapy that offers improvements in dosimetry in many
      clinical scenarios. Here we review the clinical evidence for IMRT and present
      ongoing or unpublished randomised controlled trials (RCTs). METHODS: We
      identified randomised and non-randomised comparative studies of IMRT and
      conventional radiotherapy using MEDLINE, hand-searching Radiotherapy and Oncology
      and the International Journal of Radiation Oncology, Biology and Physics and the
      proceedings of the American Society for Therapeutic Radiology and Oncology and
      the European Society for Therapeutic Radiology and Oncology annual meetings. The
      metaRegister of Controlled Trials was searched to identify completed-unpublished,
      ongoing and planned RCTs. RESULTS: Sixty-one studies comparing IMRT and
      conventional radiotherapy were identified. These included three RCTs in head and
      neck cancer (205 patients) and three in breast cancer (664 patients) that had
      reported clinical outcomes; these were all powered for toxicity-related end
      points, which were significantly better with IMRT in each trial. There were 27
      additional non-randomised studies in head and neck (1119 patients), 26 in
      prostate cancer (>5000 patients), four in breast cancer (875 patients) and nine
      in other tumour sites. The results of these studies supported those of the RCTs
      with benefits reported in acute and late toxicity, health-related quality of life
      and tumour control end points. Twenty-eight completed-unpublished, ongoing or
      planned RCTs incorporating IMRT were identified, including at least 12,310
      patients, of which 15 compared conventional radiotherapy within IMRT as a
      randomisation or pre-planned stratification. DISCUSSION: Inverse-planned IMRT
      maintains parotid saliva production and reduces acute and late xerostomia during
      radiotherapy for locally advanced head and neck cancer, reduces late rectal
      toxicity in prostate cancer patients allowing safe dose escalation and seems to
      reduce toxicity in several other tumour sites. Forward-planned IMRT reduces acute
      toxicity and improves late clinician-assessed cosmesis compared with conventional
      tangential breast radiotherapy.

PMID- 20673709
TI  - UK guidelines for the safe delivery of intensity-modulated radiotherapy.
AB  - This paper outlines the guidelines for the development of intensity-modulated
      radiotherapy (IMRT) in the UK. The guidelines are designed to cover the complete
      implementation of IMRT, with guidelines in the following categories:
      commissioning, quality, clinical, audit, and training and education. These
      guidelines have been compiled by the Radiotherapy Development Board of the Royal
      College of Radiologists and will support the safe application of IMRT in the UK.

PMID- 20673710
TI  - Fatty acid metabolism in cystic fibrosis.
AB  - Despite identification twenty years ago of the gene responsible for cystic
      fibrosis transmembrane conductance regulator (CFTR), the protein defective in
      cystic fibrosis (CF), research of this monogenetic disease has not provided an
      explanation for the divergent symptoms, and a treatment breakthrough is still
      awaited. This review discusses different aspects of disturbances in lipid
      metabolism seen in CF. These include increased release of arachidonic acid (AA)
      from cell membrane phospholipids and a low status of linoleic and docosahexaenoic
      acids. Recent research has explored more complicated lipid associations.
      Disturbances in annexins and ceramides might act in concert to explain the impact
      on inflammation and AA release. The connections to CFTR and between the
      disturbances in essential fatty acid metabolism are reviewed. The metabolic
      interactions, some of which might be compensating, possibly explain the
      difficulties in understanding the fatty acid disturbances in relation to
      different symptoms and their relation to the defective CFTR.

PMID- 20673711
TI  - Sustainable disposal of municipal solid waste: post bioreactor landfill
      polishing.
AB  - Sustainable disposal of municipal solid waste (MSW) requires assurance that
      contaminant release will be minimized or prevented within a reasonable time frame
      before the landfill is abandoned so that the risk of contamination release is not
      passed to future generations. This could be accomplished through waste acceptance
      criteria such as those established by the European Union (EU) that prohibit land
      disposal of untreated organic matter. In the EU, mechanical, biological and/or
      thermal pretreatment of MSW is therefore necessary prior to landfilling which is
      complicated and costly. In other parts of the world, treatment within highly
      engineered landfills is under development, known as bioreactor landfills.
      However, the completed bioreactor landfill still contains material, largely
      nonbiodegradable carbon and ammonia that may be released to the environment over
      the long-term. This paper provides a conceptual analysis of an approach to ensure
      landfill sustainability by the rapid removal of these remaining materials,
      leachate treatment and recirculation combined with aeration. The analysis in this
      paper includes a preliminary experimental evaluation using real mature leachate
      and waste samples, a modeling effort using a simplified mass balance approach and
      input parameters from real typical bioreactor cases, and a cost estimate for the
      suggested treatment method.

PMID- 20673712
TI  - Detection of refractive index changes in individual living cells by means of
      surface plasmon resonance imaging.
AB  - Real time imaging of living cell activation is an increasing demand in
      disciplines of life science and medicine. We previously reported that surface
      plasmon resonance (SPR) sensors detect large changes of refractive index with
      living cells, such as mast cells, keratinocyte, human basophils and B-cells
      activated by biological stimuli. However, conventional SPR sensors detect only an
      average change of refractive index with thousands of cells at detectable area on
      a sensor chip. In this study, we developed an SPR imaging (SPRI) sensor with a
      CMOS camera and an objective lens in order to analyze refractive index of
      individual living cells and their changes upon stimuli. The SPRI sensor could
      detect reactions of individual rat basophilic leukemia (RBL-2H3) cells, mouse
      keratinocyte (PAM212) cells, and human epidermal carcinoma (A431) cells in
      response to either specific or non-specific stimuli, such as antigen, phorbol
      ester or epidermal growth factor, with or without their inhibitors, resembling
      signals obtained by a conventional SPR sensor. Moreover, we distinguished
      reactions of different type cells, co-cultured on a sensor chip, and revealed
      that the increase of refractive index around nuclei is rapid and potent as
      compared to that in peripheries in the reaction of RBL-2H3 cells against antigen.
      This system may be a useful tool to investigate the mechanism of refractive index
      changes evoked in near-membrane fields of living cells, and to develop a system
      of high-throughput screening for clinical diagnosis.

PMID- 20673713
TI  - Optimization of ricotta cheese whey (RCW) fermentation by response surface
      methodology.
AB  - A central composite design (CCD) was performed to evaluate the effects of four
      factors, i.e. temperature (T), pH, agitation rate (K) and initial lactose
      concentration (L), on ricotta cheese whey batch fermentation and to optimize the
      process leading to the formation of bio-ethanol. Anaerobic batch fermentation
      experiments were carried out by using the yeast Kluyveromyces marxianus. After a
      preliminary experimental analysis, the values of the chosen factors were 32 and
      40 degrees C for T, 4 and 6 for pH, 100 and 300 rpm for K, 40 and 80 g L(-1) for
      L. Response surface methodology (RSM) was used to optimize the fermentation
      process and an empirical polynomial model was used to fit the experimental data.
      The best operating conditions resulted to be T=32.35 degrees C, pH 5.41, K=195.56
      rpm and L=40 g L(-1) and the model ensured a good fitting of the observed data.

PMID- 20673714
TI  - Bio-oil from photosynthetic microalgae: case study.
AB  - Microalgae possess the potential to produce bio-oils, carbohydrates, protein,
      amino acids and other value added products, each of which increase its value as a
      crop. Unfortunately, proven systems do not yet exist for commercial scale
      production. System designs have generally not adequately accounted for water and
      energy use at scale, as well as byproduct markets, and thus yielded systems that
      are both unaffordable and unsustainable. We address energy and water use by
      presenting a straightforward microalga-to-bio-oil production process and then
      characterize system performance using steady-state water and energy balances.
      Practical limitations to commercial production of bio-oils from photosynthetic
      microalgae are proposed and conclusions drawn regarding system potential for
      assumed biomass productivities. As this is a theoretical analysis of a generic
      process and in practice many of the bottlenecks presented remain to be solved, it
      is our intent that the analysis framework presented herein can be applied to
      future systems that propose such solutions.

PMID- 20673715
TI  - Catalysis of the electrochemical reduction of oxygen by bacteria isolated from
      electro-active biofilms formed in seawater.
AB  - Biofilms formed in aerobic seawater on stainless steel are known to be efficient
      catalysts of the electrochemical reduction of oxygen. Based on their genomic
      analysis, seven bacterial isolates were selected and a cyclic voltammetry (CV)
      procedure was implemented to check their electrocatalytic activity towards oxygen
      reduction. All isolates exhibited close catalytic characteristics. Comparison
      between CVs recorded with glassy carbon and pyrolytic graphite electrodes showed
      that the catalytic effect was not correlated with the surface area covered by the
      cells. The low catalytic effect obtained with filtered isolates indicated the
      involvement of released redox compounds, which was confirmed by CVs performed
      with adsorbed iron-porphyrin. None of the isolates were able to form electro
      active biofilms under constant polarization. The capacity to catalyze oxygen
      reduction is shown to be a widespread property among bacteria, but the property
      detected by CV does not necessarily confer the ability to achieve stable oxygen
      reduction under constant polarization.

PMID- 20673716
TI  - In situ encapsulation of laccase in microfibers by emulsion electrospinning:
      preparation, characterization, and application.
AB  - Laccase from Trametes versicolor was successfully in situ encapsulated into the
      poly(D,L-lactide) (PDLLA)/PEO-PPO-PEO (F108) electrospun microfibers by emulsion
      electrospinning. The porous morphology of electrospun microfibers was observed
      with scanning electron microscope, and the core-shell structure of microfibers
      and existence of laccase in microfibers were proved by laser confocal scanning
      microscopy micrograph. In this study, fibrous porosity and core-shell structure
      are advantageous to the activity and stability preservation of immobilized
      laccase. The activity of immobilized laccase could retain over 67% of that of the
      free enzyme. After 10 successive runs in the enzyme reactor, the immobilized
      laccase could also maintain 50% of its initial activity. Crystal violet dye was
      successfully degraded by the PDLLA/F108-laccase electrospun microfiber membranes.
      It was observed that the immobilized laccase possessed a broadening pH range of
      catalysis activity compared to free laccase.

PMID- 20673717
TI  - Discovery and structure-activity relationships of a series of pyroglutamic acid
      amide antagonists of the P2X7 receptor.
AB  - A computational lead-hopping exercise identified compound 4 as a structurally
      distinct P2X(7) receptor antagonist. Structure-activity relationships (SAR) of a
      series of pyroglutamic acid amide analogues of 4 were investigated and compound
      31 was identified as a potent P2X(7) antagonist with excellent in vivo activity
      in animal models of pain, and a profile suitable for progression to clinical
      studies.

PMID- 20673718
TI  - Addressing time-dependent CYP 3A4 inhibition observed in a novel series of
      substituted amino propanamide renin inhibitors, a case study.
AB  - Time-dependent inhibitors of CYPs have the potential to perpetrate drug-drug
      interactions in the clinical setting. After finding that several leading
      compounds in a novel series of substituted amino propanamide renin inhibitors
      inactivated CYP3A4 in an NADPH-dependent and time-dependent manner, a search to
      identify the cause of this liability was initiated. Extensive SAR revealed that
      the amide bridge present in compound 1 as a possible culprit. Through the
      installation of a metabolic soft spot distal to this moiety, potent renin
      inhibitors with improved CYP profile were identified.

PMID- 20673719
TI  - Discovery and expanded SAR of 4,4-disubstituted quinazolin-2-ones as potent T
      type calcium channel antagonists.
AB  - The discovery and synthesis of 4,4-disubstituted quinazolinones as T-type calcium
      channel antagonists is reported. Based on lead compounds 2 and 3, a focused SAR
      campaign driven by the optimization of potency, metabolic stability, and
      pharmacokinetic profile identified 45 as a potent T-type Ca(2+) channel
      antagonist with minimized PXR activation. In vivo, 45 suppressed seizure
      frequency in a rat model of absence epilepsy and showed significant alterations
      of sleep architecture after oral dosing to rats as measured by EEG.

PMID- 20673720
TI  - Fourth ventricular chordoid meningioma.
AB  - The chordoid variant of meningioma is a histological subtype which carries with
      it a more aggressive clinical course and a propensity for recurrence. Similar to
      other meningioma subtypes, this lesion is encountered typically in the
      supratentorial compartment, often along the cerebral convexities. The chordoid
      meningioma subtype is found primarily in the adult population, and may
      occasionally be associated with the systemic manifestations of Castleman's
      disease. We present an adult patient with a rare chordoid meningioma located
      within the fourth ventricle. This lesion was treated with gross total resection.
      Chordoid meningioma must be considered within the differential diagnosis of
      intraventricular tumors. This histological subtype of meningioma warrants close
      follow-up. The patient must also be evaluated for systemic manifestations of
      Castleman's disease.

PMID- 20673721
TI  - Unilateral craniotomy for bilateral cerebral aneurysms.
AB  - Multiple intracranial aneurysms located bilaterally in the anterior circulation
      are usually clipped sequentially by separate craniotomies or a bilateral
      craniotomy. However, in selected patients, bilateral aneurysms can be clipped on
      both sides in a single sitting through a unilateral approach and unilateral
      craniotomy without causing morbidity. We present our technique and results of
      bilateral aneurysms clipped through a unilateral craniotomy from the ruptured
      aneurysm side. Ten patients (between 2006 and 2008) aged 20years to 67years with
      bilateral supratentorial anterior circulation saccular aneurysms, World
      Federation of Neurological Surgeons Scale (WFNS) score subarachnoid hemorrhage
      (SAH) grades 1 and 3, Fisher grades 2 and 3, were operated with unilateral orbito
      pterional craniotomy and clipping of bilateral aneurysms. A total of 23
      aneurysms, 12 located contralaterally, were successfully clipped with a good
      outcome in nine patients and no mortality at all. We therefore conclude that the
      unilateral orbito-pterional approach can be safely employed in selected patients
      harboring bilateral supratentorial saccular aneurysms and presenting with SAH,
      having WFNS grade 1 to 3, Fisher grade up to grade 3. The brain must be lax intra
      operatively. Wide opening of the basal cisterns, 3rd ventriculostomy, and
      clipping of ruptured aneurysms are the important steps to be performed first
      before clipping the contralateral aneurysm thus avoiding a second craniotomy.

PMID- 20673722
TI  - New 4H-chromen-4-one and 2H-chromene derivatives as anti-picornavirus capsid
      binders.
AB  - Substituted (E)-3-styryl-4H-chromen-4-ones 1a-d, 3-[(1E,3E)-4-phenylbuta-1,3
      dienyl]-4H-chromen-4-ones 2a-d, (E)-3-styryl-2H-chromenes 3a-d and 3-[(1E,3E)-4
      phenylbuta-1,3-dienyl]-2H-chromenes 4a-d were designed and synthesized to improve
      the anti-picornavirus activity of previously tested analogues. The new compounds
      were evaluated in vitro against human rhinovirus (HRV) serotypes 1B and 14 and
      enterovirus (EV) 71. All the compounds interfered with the replication of
      picornaviruses, although considerable differences were observed in the
      sensitivity of viruses to each compound. Generally, both HRVs were more
      susceptible than EV71 and their sensitivity was dependent upon the linker chain
      length as well as upon the oxidation state of the heterocyclic ring. (E)-3-Styryl
      2H-chromene (3a) emerged as the most effective inhibitor of both HRVs showing
      IC(50) values of 0.20 microM and 1.38 microM towards serotype 1B and 14,
      respectively. The potent activity was also coupled with low cytotoxicity
      resulting in high therapeutic indexes (250 and 36, respectively). Mechanism of
      action studies indicated that 3a, like structurally related compounds, behaves as
      a capsid binder interfering with the early stages of rhinovirus infection,
      probably at the adsorption and/or uncoating level.

PMID- 20673723
TI  - Conjugates of betulin derivatives with AZT as potent anti-HIV agents.
AB  - Fourteen novel conjugates of 3,28-di-O-acylbetulins with AZT were prepared as
      anti-HIV agents, based on our previously reported potent anti-HIV triterpene
      leads, including 3-O-acyl and 3,28-di-O-acylbetulins. Nine of the conjugates (49
      53, 55, 56, 59, and 60) exhibited potent anti-HIV activity at the submicromolar
      level, with EC(50) values ranging from 0.040 to 0.098muM in HIV-1(NL4-3) infected
      MT-4 cells. These compounds were equipotent or more potent than 3-O-(3',3'
      dimethylsuccinyl)betulinic acid (2), which is currently in Phase IIb anti-AIDS
      clinical trial.

PMID- 20673725
TI  - Design, synthesis and anticholinesterase activity of a novel series of 1-benzyl-4
      ((6-alkoxy-3-oxobenzofuran-2(3H)-ylidene) methyl) pyridinium derivatives.
AB  - A novel series of benzofuranone-ylidene-methyl benzylpyridinium derivatives (6a
      u) were synthesized as acetylcholinesterase inhibitors. The anticholinesterase
      activity of synthesized compounds was measured using colorimetric Ellman's
      method. It was revealed that some synthesized compounds exhibited high
      anticholinesterase activity, among them compound 6b was the most active compound
      (IC(50)=10 + or - 6.87 nM).

PMID- 20673724
TI  - Structure-based design, synthesis, and biological evaluation of lipophilic-tailed
      monocationic inhibitors of neuronal nitric oxide synthase.
AB  - Selective inhibitors of neuronal nitric oxide synthase (nNOS) have the potential
      to develop into new neurodegenerative therapeutics. Recently, we described the
      discovery of novel nNOS inhibitors (1a and 1b) based on a cis-pyrrolidine
      pharmacophore. These compounds and related ones were found to have poor blood
      brain barrier permeability, presumably because of the basic nitrogens in the
      molecule. Here, a series of monocationic compounds was designed on the basis of
      docking experiments using the crystal structures of 1a,b bound to nNOS. These
      compounds were synthesized and evaluated for their ability to inhibit neuronal
      nitric oxide synthase. Despite the excellent overlap of these compounds with 1a,b
      bound to nNOS, they exhibited low potency. This is because they bound in the nNOS
      active site in the normal orientation rather than the expected flipped
      orientation used in the computer modeling. The biphenyl or phenoxyphenyl tail is
      disordered and does not form good protein-ligand interactions. These studies
      demonstrate the importance of the size and rigidity of the side chain tail and
      the second basic amino group for nNOS binding efficiency and the importance of
      the hydrophobic tail for conformational orientation in the active site of nNOS.

PMID- 20673726
TI  - Design, synthesis, and cholesterol-lowering efficacy for prodrugs of
      berberrubine.
AB  - In order to enhance oral bioavailability of berberine (BBR) for its cholesterol
      lowering efficacy in vivo, a series of ester or ether prodrugs of berberrubine
      (M1), which is an active metabolite of BBR after first-pass metabolism, were
      designed, semi-synthesized, and evaluated. Among these M1 prodrugs, compound 5g
      possessing palmitate at the 9-position showed a moderate LogP value and esterase
      hydrolysis rate for releasing M1 in blood. Its cholesterol-lowering efficacy in
      vivo was evaluated in hyperlipidemic SD rats. Compound 5g (100mg/kg/d) reduced
      blood CHO and LDL-c by 35.8% and 45.5%, respectively, similar to that by BBR. It
      also exhibited a good safety in rats with no side-effect on liver and kidney
      function. Therefore, the design of M1 prodrug appears to be an effective strategy
      to improve pharmacokinetic feature of BBR for its lipid-lowering efficacy in
      vivo.

PMID- 20673727
TI  - Synthesis, biological evaluation, and structure-activity relationship study of
      novel cytotoxic aza-caffeic acid derivatives.
AB  - Three series of aza-caffeic acid derivatives with different linkers were designed
      and synthesized. Each of the synthesized derivatives was then used in
      cytotoxicity screening on either 8 or 12 human cancer cell lines. The structure
      activity relationships on three structural regions A, B, and C are analyzed in
      detail, indicating that a nine bond linker B, containing a piperazine unit, is
      the most favorable linker leading to the generation of molecules with potent
      cytotoxicities. Compound (E)-1-(4-(3,4-dichlorobenzyl)piperazin-1-yl)-3-(4-(4
      ethoxybenzyloxy)-3,5-dimethoxyphenyl)prop-2-en-1-one (80) exhibited the most
      significant and selective cytotoxicity to KB, BEL7404, K562, and Eca109 cell
      lines, with IC(50) values of 0.2, 2.0, 1.7, and 1.1 microM, respectively,
      stronger than that seen for caffeic acid phenethyl ester (CAPE) and cisplatin
      (CDDP). Flow cytometric and western blot analysis indicate that compound 80 plays
      a role in mitochondria-dependent apoptosis activity by suppressing K562 cell
      proliferation in a concentration- and time-dependent manner.

PMID- 20673728
TI  - Discovery of achiral inhibitors of the hepatitis C virus NS3 protease based on
      2(1H)-pyrazinones.
AB  - Herein, the design, synthesis and inhibitory potency of a series of novel
      hepatitis C virus (HCV) NS3 protease inhibitors are presented. These inhibitors
      are based on a 2(1H)-pyrazinone P3 scaffold in combination with either a P2
      phenylglycine or a glycine, and they were evaluated on the wild type as well as
      on two resistant variants of the enzyme, A156T and D168V. Molecular modelling
      suggested that the aromatic side-chain of the P2 phenylglycine occupies the same
      space as the substituent in position 6 on the pyrazinone core. The versatile
      synthetic route applied for the pyrazinone synthesis made a switch between the
      two positions easily feasible, resulting in phenyl- or benzyl substituted
      pyrazinones and leaving glycine as the P2 residue. Of several P1-P1' residues
      evaluated, an aromatic P1-P1' scaffold was found superior in combination with the
      new P3-P2 building block. As a result, an entirely new type of achiral and
      rigidified inhibitors was discovered, with the best of the novel inhibitors
      having fourfold improved potency compared to the corresponding tripeptide lead.
      We consider these achiral inhibitors highly suitable as starting points for
      further optimization.

PMID- 20673729
TI  - Discovery of 2-(4-((1H-1,2,4-triazol-1-yl)methyl)-5-(4-bromophenyl)-1-(2
      chlorophenyl)-1H-pyrazol-3-yl)-5-tert-butyl-1,3,4-thiadiazole (GCC2680) as a
      potent, selective and orally efficacious cannabinoid-1 receptor antagonist.
AB  - Structure-activity relationship studies in a series of diarylpyrazolyl
      thiadiazoles identified cannabinoid-1 receptor antagonists with excellent potency
      and selectivity. Based on its exceptional in vivo efficacy in animal models and
      its favorable pharmacokinetic and toxicological profiles, 2-(4-((1H-1,2,4-triazol
      1-yl)methyl)-5-(4-bromophenyl)-1-(2-chlorophenyl)-1H-pyrazol-3-yl)-5-tert-butyl
      1,3,4-thiadiazole (GCC2680) was selected as a preclinical candidate for the
      treatment of obesity.

PMID- 20673730
TI  - 3D histomorphometric quantification of trabecular bones by computed
      microtomography using synchrotron radiation.
AB  - Conventional bone histomorphometry is an important method for quantitative
      evaluation of bone microstructure. X-ray computed microtomography is a non
      invasive technique, which can be used to evaluate histomorphometric indices in
      trabecular bones (BV/TV, BS/BV, Tb.N, Tb.Th, Tb.Sp). In this technique, 3D images
      are used to quantify the whole sample, differently from the conventional one, in
      which the quantification is performed in 2D slices and extrapolated for 3D case.
      In this work, histomorphometric quantification using synchrotron 3D X-ray
      computed microtomography was performed to quantify the bone structure at
      different skeletal sites as well as to investigate the effects of bone diseases
      on quantitative understanding of bone architecture. The images were obtained at
      Synchrotron Radiation for MEdical Physics (SYRMEP) beamline, at ELETTRA
      synchrotron radiation facility, Italy. Concerning the obtained results for normal
      and pathological bones from same skeletal sites and individuals, from our
      results, a certain declining bone volume fraction was achieved. The results
      obtained could be used in forming the basis for comparison of the bone
      microarchitecture and can be a valuable tool for predicting bone fragility.

PMID- 20673731
TI  - Three-dimensional mandibular motion after closed and open reduction of unilateral
      mandibular condylar process fractures.
AB  - OBJECTIVE: To detect the changes in 3D mandibular motion after two types of
      condylar fracture therapies. MATERIALS AND METHODS: Using a 3D motion analyzer,
      free mandibular border movements were recorded in 21 patients successfully
      treated for unilateral fractures of the mandibular condylar process (nine
      patients: open reduction, rigid internal fixation, and functional treatment; 12
      patients: closed reduction and functional treatment; follow-up: 6-66 months), and
      in 25 control subjects. RESULTS: No differences were found among the groups at
      maximum mouth opening (MO), protrusion and in lateral excursions. During opening,
      the patients had a larger maximal deviation to the fractured side than the
      controls (controls 2.3 mm, open treatment 3.9 mm, closed treatment 4.2 mm;
      Kruskal-Wallis test, p=0.014; closed treatment vs. controls, p=0.004), with a
      larger coronal plane angle (controls 2.4 degrees , open treatment 3.6 degrees ,
      closed treatment 4.4 degrees ; p=0.016; closed treatment vs. controls, p=0.013).
      In the closed treatment patients, a longer follow-up was related to increased
      maximum MO (p=0.04), sagittal plane angle (p=0.03), and reduced lateral
      mandibular deviation during MO (p=0.03). CONCLUSION: Mandibular condylar
      fractures can recover good function; some kinematic variables of mandibular
      motion were more similar to the norm in the open treatment patients than in
      closed treatment patients.

PMID- 20673732
TI  - The impact of localized fatigue on contralateral tremor and muscle activity is
      exacerbated by standing posture.
AB  - Physiological tremor is an inherent feature of the motor system that is
      influenced by intrinsic (neuromuscular) and/or extrinsic (task) factors. Given
      that tremor must be accounted for during the performance of many fine motor
      skills; there is a requirement to clarify how different factors interact to
      influence tremor. This study was designed to assess the impact localized fatigue
      of a single arm and stance position had on bilateral physiological tremor and
      forearm muscle activity. Results demonstrated that unilateral fatigue produced
      bilateral increases in tremor and wrist extensor activity. For example, fatigue
      resulted in increases in extensor activity across both exercised (increased 8-10%
      MVC) and the non-exercised arm (increased 3-7% MVC). The impact of fatigue was
      not restricted to changes in tremor/EMG amplitude, with altered hand-finger
      coupling observed within both arms. Within the exercised arm, cross-correlation
      values decreased (pre-exercise r=0.62-0.64; post-exercise r=0.37-0.43) while
      coupling increased within the non-exercised arm (pre-exercise r=0.51-0.55; post
      exercise r=0.62-0.67). While standing posture alone had no significant impact on
      tremor/EMG dynamics, the tremor and muscle increases seen with fatigue were more
      pronounced when standing. Together these results demonstrate that the combination
      of postural and fatigue factors can influence both tremor/EMG outputs and the
      underlying coordinative coupling dynamics.

PMID- 20673733
TI  - Distribution and morphology of the juxtapositions between growth hormone
      releasing hormone-(ghrh)-immunoreactive neuronal elements.
AB  - Previous studies revealed that growth hormone-releasing hormone (GHRH)
      immunoreactive (IR) neurons form a circumscribed cell group in the basal
      infundibulum/median eminence of the human hypothalamus. GHRH from these neurons
      is released into the hypothalamo-hypophyseal portal circulatory system in a
      pulsatile manner. It is a common consensus that the pulsatile release of GHRH is
      the main driving force behind the pulsatile release of growth hormone (GH) and
      may contribute to the regulation of other hypothalamic functions. The pulsatile
      release of GHRH requires synchronized activity of GHRH-IR neurons. However, the
      morphological basis of this synchronization between the GHRH-IR neural elements
      has not been elucidated yet. Since the utilization of electron microscopy
      combined with immunohistochemistry is virtually impossible in the human brain due
      to the long post mortem period, immunohistochemistry, evaluated with oil
      immersion light microscopy, was used in order to reveal the associations between
      the GHRH elements. Numerous GHRH-GHRH juxtapositions have been detected in the
      infundibular area/median eminence, where GHRH-IR axonal varicosities often formed
      multiple contacts with GHRH-IR perikarya. Examination of these associations with
      high magnification oil immersion light microscopy revealed (1) axonal swellings
      at the site of the contacts and (2) no gaps between the contacting elements
      suggesting that these juxtapositions may be functional synapses. The large number
      of GHRH-GHRH juxtapositions in the infundibular area/median eminence suggests
      that these synapse-like structures may represent the morphological substrate of
      the synchronized activity of GHRH neurons that in turn may result in the
      pulsatile release of GHRH in human.

PMID- 20673734
TI  - Clofarabine for treatment of acute lymphoblastic leukaemia in adults.

PMID- 20673735
TI  - [Depression in oncology].
AB  - The purpose of this paper was to make a brief review of the main problematics
      raised by depression in oncology in terms of prevalence, semiology, screening,
      risk, prognosis factors and treatment. This reflection was based on recent
      literature data obtained through a PubMed search. Depressive disorders have
      frequently been encountered in cancer patients. During routine oncology daily
      care, depression screening, assessment and treatment are of paramount importance
      regarding psychosocial management. Depressive elements have a tremendous impact
      on the quality of life, tolerance and compliance with anticancer treatment.
      Moreover, depression morbidity and its possible influence on prognosis represent
      an important challenge in terms of prevention. A specific semiology for
      depressive disorders in the oncologic field might be more relevant with practical
      clinical implications. Optimal care of these mood disorders have to be
      implemented as soon as possible and be supported by the association of
      pharmacological treatment and psychotherapy.

PMID- 20673736
TI  - [Solitary and extramedullary plasmocytoma in the head and neck region: five cases
      report].
AB  - PURPOSE: To assess the outcome and the management of solitary extramedullary
      plasmocytoma in the head and neck region. PATIENTS AND METHODS: From 1997 to
      2008, five cases of solitary extramedullary plasmocytoma were treated in the
      department of radiotherapy at Salah-Azaiz Institute. Three patients had a
      solitary plasmocytoma of the nasal fossa; the others were ethmoidal and
      submandibular node. All patients received irradiation of 40 to 45 Gy in the
      primary site associated to surgery in four cases. Among the five patients, two
      had radiotherapy after recurrence. RESULTS: Four complete responses were noted
      with a follow-up of 12, 36, 52 and 72 months. Multiple myeloma occurred in one
      patient 8 years after treatment. CONCLUSION: Radiotherapy is the best effective
      local treatment. Local control of extramedullary plasmocytoma in the head and
      neck region seems to be improved when the dose is at least 45 Gy. Predictive
      parameters of unfavourable outcome and conversion of extramedullary plasmocytoma
      to multiple myeloma should be better defined.

PMID- 20673737
TI  - Gating and tracking, 4D in thoracic tumours.
AB  - The limited ability to control for a tumour's location compromises the accuracy
      with which radiation can be delivered to tumour-bearing tissue. The resultant
      requirement for larger treatment volumes to accommodate target uncertainty
      restricts the radiation dose because more surrounding normal tissue is exposed.
      With image-guided radiation therapy (IGRT), these volumes can be optimized and
      tumouricidal doses may be delivered, achieving maximum tumour control with
      minimal complications. Moreover, with the ability of high precision dose delivery
      and real-time knowledge of the target volume location, IGRT has initiated the
      exploration of new indications in radiotherapy such as hypofractionated
      radiotherapy (or stereotactic body radiotherapy), deliberate inhomogeneous dose
      distributions coping with tumour heterogeneity (dose painting by numbers and
      biologically conformal radiation therapy), and adaptive radiotherapy. In short:
      "individualized radiotherapy". Tumour motion management, especially for thoracic
      tumours, is a particular problem in this context both for the delineation of
      tumours and organs at risk as well as during the actual treatment delivery. The
      latter will be covered in this paper with some examples based on the experience
      of the UZ Brussel. With the introduction of the NOVALIS system (BrainLAB,
      Feldkirchen, Germany) in 2000 and consecutive prototypes of the ExacTrac IGRT
      system, gradually a hypofractionation treatment protocol was introduced for the
      treatment of lung tumours and liver metastases evolving from motion-encompassing
      techniques towards respiratory-gated radiation therapy with audio-visual feedback
      and most recently dynamic tracking using the VERO system (BrainLAB, Feldkirchen,
      Germany). This evolution will be used to illustrate the recent developments in
      this particular field of research.

PMID- 20673738
TI  - The final stage of the collapse of a cloud of bubbles close to a rigid boundary.
AB  - The final stage of the collapse of a hemispherical cloud of bubbles close to a
      rigid boundary was investigated by ultra high-speed photography with up to 200
      million frames/s. Our investigations reveal two types of secondary shock wave
      emission during cloud rebound. In the first case, the secondary shock wave
      emission is a consequence of the free collapse of a bubble within the cloud by
      the ambient pressure in the fluid. In the second case, it is a consequence of the
      interaction of the cloud-collapse-induced shock wave with microbubbles situated
      close to the collapse site of the cloud. The latter can be very powerful,
      resulting in a secondary shock wave emission with a maximum amplitude of about
      0.5 GPa.

PMID- 20673739
TI  - Percept-based and object-based error processing: an experimental dissociation of
      error-related negativity and error positivity.
AB  - OBJECTIVE: Investigated the effect of presentation duration of masked visual
      stimuli and presentation mode (randomized, blocked) on error-related negativity
      (ERN) and error positivity (Pe). METHOD: In two experiments, participants
      responded with the left and right hand to leftward and rightward arrows presented
      for different durations (0-117 ms). Different stimulus durations were fully
      randomized in Experiment 1 but run in separate blocks in Experiment 2. RESULTS:
      In both experiments, percent correct and Pe amplitude increased with increasing
      stimulus duration. By contrast, ERN was only found for (blocked) longer stimulus
      durations of Experiment 2, and absent with the randomized stimulus durations of
      Experiment 1. CONCLUSIONS: Presence of a Pe in the absence of ERN in Experiment 1
      suggests that conscious error processing can occur without prior unconscious
      error detection. To explain the pattern of ERN/Pe effects, two separate processes
      of error detection are suggested, operating independently at the levels of object
      based (Pe) and purely perceptual stimulus representations (ERN), respectively.
      SIGNIFICANCE: A novel model of error processing is developed, elaborating on the
      reinforcement-learning theory of ERN. It is suggested that giving a response
      retrieves appropriate stimulus representations whose activation typically
      precedes this response; in case of mismatch with actually present stimuli, ERN is
      elicited.

PMID- 20673740
TI  - Current status on electrodiagnostic standards and guidelines in neuromuscular
      disorders.
AB  - The aim of this review is to present the status of electrodiagnostic standards
      and guidelines in neuromuscular disorders. Electrodiagnostic guidelines are
      developed on the background of medical technology assessment, wherefore a short
      presentation of medical technology assessment is given covering: (1) Evidence
      based medicine, i.e. "to do the right thing", describing practice parameters and
      the STARD initiative which introduces evidence-based medicine in
      electrodiagnostic medicine, (2) Continuous quality improvement, i.e. "to do the
      thing right", describing variation among laboratories in methods and
      interpretation of tests, and the need for medical audit and implementation of
      electrodiagnostic guidelines, (3) Outcome studies, i.e. "is it worthwhile to do
      the right thing right?". In electrodiagnostic medicine there are very few outcome
      studies. Standards and guidelines described in the literature for different
      neuromuscular disorders are presented, often as figures or tables. These cover
      guidelines developed in detail for CIDP by expert consensus multicentre groups by
      AAN, INCAT, EFNS/PNS and for other inflammatory demyelinating neuropathies are
      described, as well as guidelines differentiating between demyelinating
      pathophysiology and axonal loss by motor and sensory nerve conduction studies.
      Furthermore, electrodiagnostic guidelines for ALS as detailed in the El Escorial,
      the modified El Escorial and the recent supplementary Awaji criteria are
      described and presented in a comprehensive table. Only few electrodiagnostic
      guidelines are published for nerve entrapment, cervical radiculopathy and
      neuromuscular transmission failure whereas none are known for myopathy. If no
      electrodiagnostic criteria for a given disorder exist, criteria for the
      electrodiagnostic examination are described if present. It is concluded that
      future research is needed in order to develop more electrodiagnostic guidelines
      in neuromuscular disorders by international expert consensus groups. Such
      research should use an evidence-based medicine approach and medical technology
      assessment and include continuous quality development and outcome studies.

PMID- 20673741
TI  - Sleep maintenance insomnia complaints predict poor CPAP adherence: A clinical
      case series.
AB  - BACKGROUND: Although CPAP is a highly efficacious treatment for obstructive sleep
      apnea (OSA), low adherence presents a significant challenge for sleep medicine
      clinicians. The present study aimed to evaluate the relationship between insomnia
      symptoms and CPAP use. We hypothesized that pre-treatment insomnia complaints
      would be associated with poorer CPAP adherence at clinical follow-up. METHODS:
      This was a retrospective chart review of 232 patients (56.5% men, mean age=53.6+/
      12.4years) newly diagnosed with OSA (mean AHI=41.8+/-27.7) and prescribed CPAP in
      the Johns Hopkins Sleep Disorder Center. Difficulty initiating sleep, difficulty
      maintaining sleep, and early morning awakening were measured via three self
      report items. CPAP use was measured via objective electronic monitoring cards.
      RESULTS: Thirty-seven percent of the sample reported at least one frequent
      insomnia complaint, with 23.7% reporting difficulty maintaining sleep, 20.6%
      reporting early morning awakening and 16.6% reporting difficulty initiating
      sleep. After controlling for age and gender, sleep maintenance insomnia displayed
      a statistically significant negative relationship with average nightly minutes of
      CPAP use (p<.05) as well as adherence status as defined by the Centers for
      Medicaid and Medicare Services (p<.02). CONCLUSIONS: To our knowledge, these are
      the first empirical data to document that insomnia can be a risk factor for
      poorer CPAP adherence. Identifying and reducing insomnia complaints among
      patients prescribed CPAP may be a straightforward and cost-effective way to
      increase CPAP adherence.

PMID- 20673742
TI  - Sleepiness is not always perceived before falling asleep in healthy, sleep
      deprived subjects.
AB  - OBJECTIVE: To test whether subjects spontaneously signal sleepiness before
      falling asleep under monotonous conditions. METHODS: Twenty-eight healthy
      students were deprived of sleep for one night and then underwent a "maintenance
      of-wakefulness test" (MWT) consisting of four 40-min trials. They were told to
      give a signal as soon as they felt sleepy and to try to stay awake as long as
      possible. In a first series of tests, the subjects were given no reward (nr); in
      a second series, monetary rewards (wr) were given both for an accurate perception
      of sleepiness and for staying awake longer. RESULTS: Seventeen of the 28 subjects
      (60.7%) did not signal sleepiness before a sleep fragment occurred in at least
      one of the four MWT trials. Women were more reliably aware of sleepiness than men
      in the nr trials (p=.02), while the men's performance improved in the wr trials
      (p<.02), becoming equivalent to the women's performance. CONCLUSIONS: Our results
      cast doubt on the general assumption that one cannot fall asleep without feeling
      sleepy first. If similar results can be obtained in monotonous driving or working
      situations, this will imply that accidents caused by sleepiness or by falling
      asleep cannot necessarily be attributed to an individual's negligence.

PMID- 20673743
TI  - Expressions of cervical cancer-related signs and symptoms.
AB  - BACKGROUND: Cervical cancer is the second most common cancer in women worldwide.
      Although developing countries are the hardest hit by cervical cancer, women
      living in Europe are also at risk for this disease. PURPOSE OF THE STUDY: The
      purpose of the study was to explore how women treated for cervical cancer at an
      academic hospital in Tshwane, South Africa, expressed their cervical cancer
      related signs and symptoms during the initial consultation with health care
      professionals. METHODS AND SAMPLE: A qualitative, exploratory and contextual
      research design was used. The sampling method was purposive and convenience. Self
      reported data were gathered using semi-structured interviews. Diekelmann's
      hermeneutical analysis approach was used to analyze the data. The sample size
      totaled 12 (n = 12). RESULTS: Four themes emerged from the data-- ignorance,
      communication, delayed diagnosis and expectations. All participants lacked
      knowledge and awareness of the signs and symptoms of cervical cancer. The
      majority failed to communicate the real nature of their signs and symptoms and
      was only diagnosed after several visits to the primary health clinic. CONCLUSION:
      Nurses should use every opportunity to screen women for cervical cancer as the
      woman might not be able to express her cervical cancer-related signs and
      symptoms.

PMID- 20673744
TI  - Modify washing solutions in the process of deglycerolization in ACP 215 and
      storage at 4 degrees C in 0.9% sodium chloride in 24h.
AB  - BACKGROUND: The ACP 215 was a functional closed system for preparing glycerolized
      and deglycerolized RBCs, CSBT had approved the technique of long term storage
      glycerolized rare blood lower than -65 degrees C, and then deglycerolized by this
      machine. From the manual method to use ACP 215, Chinese blood banks chose 9%
      sodium chloride and 0.9% sodium chloride in deglycerolization process, while the
      AABB guideline prescribed that 12% sodium chloride and 0.9% sodium chloride-0.2%
      glucose were acceptable in washing step of ACP 215. In addition, 0.9% sodium
      chloride was the only solution which was permitted by CSBT to be added into
      postwash RBCs, while in America many kinds of additive solutions like AS-3 could
      be added into postwash RBCs and stored at 4 degrees C for 14 days. Changes of
      washing solutions and preservation solution were much different from the original
      procedure of ACP 215 approved by the FDA. It was necessary to assess the quality
      of deglyceroled and postwash RBCs by this modified process in ACP 215 in China.
      STUDY DESIGN AND METHODS: Two-unit whole bloods were collected from each
      volunteer and preserved in CP2D for anticoagulant. It was then centrifuged to
      separate the plasma, and suspending RBCs were stored at 4 degrees C in MAP for 6
      days. Each unit of RBC was transferred to a 1000-ml PVC plastic bag, an improved
      procedure including the single-disposable glycerolization set in an automated,
      functionally closed system (ACP 215, Haemonetics) was used to glycerolize RBC
      with 40% (wt/vol) glycerol, then frozen at -80 degrees C. Two modified washing
      solutions of 9% sodium chloride and 0.9% sodium chloride were used to
      deglycerolize the same RBCs with single disposable deglycerolization set in ACP
      215. The deglycerolized RBCs were stored at 4 degrees C in 0.9% sodium chloride
      for 24h. RESULTS: The freeze-thaw recovery value was 95.3+/-1.8% (mean+/-SD); the
      freeze-thaw-wash recovery value was 82.3+/-5.94% (mean+/-SD); the residure
      glycerol was 6.1+/-1.66 mg/dl (mean+/-SD), storage at 4 degrees C in 0.9% sodium
      chloride within 24h after deglycerolization the supernatant Hb was 43+/-12 mg/dl
      (mean+/-SD); the hemolysis rate was 0.2+/-0.1% (mean+/-SD); the supernatant
      potassium level was 4.03+/-0.81 mM (mean+/-SD); and the postwash units were
      negative for both aerobic and anaerobic bacteria. CONCLUSION: The postwash of
      deglycerolized RBC had an acceptable FTW recovery value, and stored in 0.9%
      sodium chloride for 24h at 4 degrees C, had an acceptable hemolysis. Modified
      washing solutions of 9% sodium chloride and 0.9% sodium chloride and without any
      of preservation had not affected the quality of frozen RBCs prepared in ACP 215
      and postwash stored at 4 degrees C in 0.9% sodium chloride within 24h.

PMID- 20673745
TI  - The neutralizing antibody response to the vaccinia virus A28 protein is
      specifically enhanced by its association with the H2 protein.
AB  - The vaccinia virus (VACV) entry-fusion complex (EFC) is composed of at least nine
      membrane proteins. Immunization of mice with individual EFC genes induced
      corresponding protein-binding antibody but failed to protect against VACV
      intranasal challenge and only DNA encoding A28 elicited low neutralizing
      antibody. Because the A28 and H2 proteins interact, we determined the effect of
      immunizing with both genes simultaneously. This procedure greatly enhanced the
      amount of antibody that bound intact virions, neutralized infectivity, and
      provided partial protection against respiratory challenge. Neither injection of
      A28 and H2 plasmids at different sites or mixing A28 and H2 sera enhanced
      neutralizing antibody. The neutralizing antibody could be completely removed by
      binding to the A28 protein alone and the epitope was located in the C-terminal
      segment. These data suggest that the interaction of H2 with A28 stabilizes the
      immunogenic form of A28, mimicking an exposed region of the entry-fusion complex
      on infectious virions.

PMID- 20673746
TI  - Switch to high-level virus replication and HLA class I upregulation in
      differentiating megakaryocytic cells after infection with pathogenic hantavirus.
AB  - Hantaan virus (HTNV), the prototype member of the Hantavirus genus in the family
      Bunyaviridae, causes hemorrhagic fever with renal syndrome (HFRS) in humans.
      Hemorrhage is due to endothelial barrier damage and a sharp decrease in platelet
      counts. The mechanisms underlying HTNV-associated acute thrombocytopenia have not
      been elucidated so far. Platelets are produced by mature megakaryocytes that
      develop during megakaryopoiesis. In this study, we show that HTNV targets
      megakaryocytic cells whereas rather non-pathogenic hantaviruses did not infect
      this cell type. After induction of differentiation megakaryocytic cells switched
      from low-level to high-level HTNV production without reduction in cell survival
      or alteration in differentiation. However, increased HTNV replication resulted in
      strong upregulation of HLA class I molecules although HTNV escaped type I
      interferon (IFN)-associated innate responses. Taken together, HTNV efficiently
      replicates in differentiating megakaryocytic cells resulting in upregulation of
      HLA class I molecules, the target structures for cytotoxic T cells (CTLs).

PMID- 20673747
TI  - A novel two-component Tobacco mosaic virus-based vector system for high-level
      expression of multiple therapeutic proteins including a human monoclonal antibody
      in plants.
AB  - Expression of multiple therapeutic proteins from Tobacco mosaic virus (TMV)-based
      vectors was not successful when plants were coinoculated with a mixture of two
      TMV vectors engineered to express two foreign genes individually. Here, we have
      engineered and developed a defective RNA (dRNA)-based TMV vector (dRT-V) that
      utilizes two components of the same virus, with the dRNA component depending on
      the helper virus for replication. Agrobacterium-mediated coinoculation of
      Nicotiana benthamiana plants with both components of the dRT-V resulted in high
      level expression of a human growth hormone and a lichenase-fused lethal factor
      protein of Bacillus anthracis. Furthermore, both heavy and light chains were
      expressed and assembled into a monoclonal antibody (mAb) specific to the
      protective antigen of B. anthracis, and the average yield of the purified
      antibody obtained was 120 mg/kg of fresh tissue. Our data suggest that dRT-V has
      a potential for rapid, cost-effective, large-scale manufacturing of multiple
      therapeutic proteins including mAbs in response to any biological emergencies.

PMID- 20673748
TI  - Pro: the FloTrac device should be used to follow cardiac output in cardiac
      surgical patients.

PMID- 20673749
TI  - Con: the FloTrac device should not be used to follow cardiac output in cardiac
      surgical patients.

PMID- 20673750
TI  - Coronary artery bypass graft surgery and moderate aortic stenosis: when to leave
      well enough alone.

PMID- 20673751
TI  - Stuck with a decision: what is the "true" aortic valve area--anatomic, geometric,
      or effective orifice area?

PMID- 20673752
TI  - The role of ultrasonography in the differentiation of the various types of
      filaricele due to bancroftian filariasis.
AB  - OBJECTIVE: (i) To determine the frequencies of urogenital pathologies in men
      infected with bancroftian filariasis, and (ii) to evaluate the role of
      ultrasonography (USG) as a diagnostic tool to differentiate between diverse
      pathologies with different clinical implications. To date, all types of scrotal
      enlargement resulting from lymphatic filariasis (LF) have been summarized under
      one term: "filaricele". PATIENTS AND METHODS: Data were compiled from recruitment
      phases for field trials in an endemic area for LF in Ghana. 1453 men aged 18
      years and above underwent ultrasound examinations of the scrotum. Observation
      parameters were: Filaria Dance Sign (FDS), dilation of supratesticular lymphatic
      vessels, thickness of scrotal skin, occurrence and amount of fluid accumulation,
      echogenicity of the fluid between the layers of the tunica vaginalis, as well as
      position and homogenicity of testis, epididymis and spermatic cord. In 1132 men,
      blood samples were taken for parasitological analysis. RESULTS: In 56% of
      examined patients, fluid accumulation around the testis was detected (38%
      subclinical-, 18% clinical stages). Differentiation of the echogenicity of the
      fluid revealed echo-free hydrocele (EFH) in 47% and echo-dense hydrocele (EDH) in
      9%. Patients without hydrocele and subclinical stages had a thinner scrotal skin
      than those in clinical stages or with lymphscrotum (P < 0.001). In the EDH group
      the scrotal skin was thicker than in the EFH group (P < 0.001). 1.4% had a
      lymphscrotum. FDS was detected in 24% of all 1453 volunteers who underwent USG.
      The number of worm nests correlated with microfilarial load and levels of
      circulating filarial antigen (P < 0.001; 20% microfilaremic, 48% antigen
      positive). CONCLUSION: In an unexpected high number of men (56%) fluid
      accumulation around the testis was detected by USG of which more than one third
      (38%) presented with subclinical stages. The study showed that echo-dense and
      echo-free fluid could be differentiated and that a considerable number of cases
      had EDH (9%) posing a risk to develop necrotic testis and infertility and
      therefore requiring immediate surgical intervention. USG thus turned out to be a
      useful diagnostic technique to differentiate between those cases requiring
      immediate surgical intervention from those that can be treated with (anti
      wolbachial and hyperpermeability reducing) drugs that ameliorate or halt
      progression of the disease.

PMID- 20673753
TI  - Multidigestion in continuous flow tandem protease-immobilized microreactors for
      proteomic analysis.
AB  - Proteolysis by sequence-specific proteases is the key step for positive
      sequencing in proteomic studies integrated with mass spectrometry (MS). The
      conventional method of in-solution digestion of protein is a time-consuming
      procedure and has limited sensitivity. In this study, we report a simple and
      rapid system for the analysis of protein sequence and protein posttranslational
      modification by multienzymatic reaction in a continuous flow using the enzyme
      (trypsin, chymotrypsin, or alkaline phosphatase)-immobilized microreactor. The
      feasibility and performance of the single microreactor and tandem microreactors
      that were connected by the different microreactors were determined by the
      digestion of nonphosphoprotein (cytochrome c) and phosphoproteins (beta-casein
      and pepsin A). The single microreactor showed rapid digestion compared with that
      of in-solution digestions. Multiple digestion by the tandem microreactors showed
      higher sequence coverage compared with that by in-solution or the single
      microreactor. Moreover, the tandem microreactor that was made by using the
      combination of protease-immobilized microreactor and phosphatase-immobilized
      microreactor showed the capability for phosphorylation site analysis in
      phosphoproteins without the use of any enrichment strategies or radioisotope
      labeling techniques. This approach provides a strategy that can be applied to
      various types of linking microreactor-based multienzymatic reaction systems for
      proteomic analysis.

PMID- 20673754
TI  - Exosome secretion of dendritic cells is regulated by Hrs, an ESCRT-0 protein.
AB  - Exosomes are nanovesicles derived from multivesicular bodies (MVBs) in antigen
      presenting cells. The components of the ESCRT (endosomal sorting complex required
      for transport) pathway are critical for the formation of MVBs, however the
      relationship between the ESCRT pathway and the secretion of exosomes remains
      unclear. We here demonstrate that Hrs, an ESCRT-0 protein, is required for
      fascilitating the secretion of exosomes in dendritic cells (DCs). Ultrastructural
      analyses showed typical saucer-shaped exosomes in the culture supernatant from
      both the control and Hrs-depleted DCs. However, the amount of exosome secretion
      was significantly decreased in Hrs-depleted DCs following stimulations with
      ovalbumin (OVA) as well as calcium ionophore. Antigen-presentation activity was
      also suppressed in exsosomes purified from Hrs-depleted DCs, while no alteration
      in OVA degradation was seen in Hrs-depleted DCs. These data indicated that Hrs is
      involved in the regulation of antigen-presentation activity through the exosome
      secretion.

PMID- 20673755
TI  - Cathepsin B-dependent motor neuron death after nerve injury in the adult mouse.
AB  - There are significant differences in the rate of neuronal death after peripheral
      nerve injury between species. The rate of neuronal death of motor neurons after
      nerve injury in the adult rats is very low, whereas that in adult mice is
      relatively high. However, the understanding of the mechanism underlying axotomy
      induced motor neuron death in adult mice is limited. Cathepsin B (CB), a typical
      cysteine lysosomal protease, has been implicated in three major morphologically
      distinct pathways of cell death; apoptosis, necrosis and autophagic cell death.
      The possible involvement of CB in the neuronal death of hypogrossal nucleus (HGN)
      neurons after nerve injury in adult mice was thus examined. Quantitative analyses
      showed the mean survival ratio of HGN neurons in CB-deficient (CB-/-) adult mice
      after nerve injury was significantly greater than that in the wild-type mice. At
      the same time, proliferation of microglia in the injured side of the HGN of CB-/-
      adult mice was markedly reduced compared with that in the wild-type mice. On the
      injured side of the HGN in the wild-type adult mice, both pro- and mature forms
      of CB markedly increased in accordance with the increase in the membrane-bound
      form of LC3 (LC3-II), a marker protein of autophagy. Furthermore, the increase in
      CB preceded an increase in the expression of Noxa, a major executor for axotomy
      induced motor neuron death in the adult mouse. Conversely, expression of neither
      Noxa or LC3-II was observed in the HGN of adult CB-/- mice after nerve injury.
      These observations strongly suggest that CB plays a critical role in axotomy
      induced mortor neuron death in adult mice.

PMID- 20673756
TI  - Effects of previous experience and associated knowledge on retrieval processes of
      faces: an ERP investigation of newly learned faces.
AB  - Conspicuously absent from face recognition research is a direct comparison of
      well-known faces with newly learned faces for which the associated biographical
      knowledge and the perceptual expertise were experimentally manipulated. Such a
      comparison can test competing assumptions made by serial and interactive
      activation and competition (IAC) models about the role of previous experience and
      biographical knowledge in face recognition. We measured behavioral performance
      and event-related potentials (ERPs) for four classes of faces: unfamiliar faces,
      faces of celebrities, and two classes of experimentally familiarized faces
      learned one week prior to the recognition test either with or without associated
      biographical knowledge. Newly learned faces associated with biographical
      knowledge showed distinct priming and old/new effects starting around 420 ms in
      the ERP when compared to faces without such information, and when compared to
      famous faces. In addition, faces for which all biographical facts were
      successfully remembered showed not only faster recognition performance than faces
      without biographical knowledge, but also a priming effect in the N170 latency.
      Previous experience including biographical knowledge associated with a face thus
      influenced retrieval processes of faces both in late, semantic and early, pre
      semantic processing stages. These findings provide novel evidence in favor of IAC
      models. In addition, famous faces had the same ERP effects as faces learned
      without associated facts. Our results show that newly learned faces are
      experimentally indistinguishable from famous faces yet provide superior
      experimental control.

PMID- 20673758
TI  - Immunolocalization of pro- and mature-brain derived neurotrophic factor (BDNF)
      and receptor TrkB in the human brainstem and hippocampus.
AB  - Brain-derived neurotrophic factor (BDNF) and its receptor TrkB are essential in
      promoting normal development of the central nervous system. Specific functions
      that are affected in knockout models include respiratory control, coordination of
      movement and balance, and feeding activities. The expression of these markers has
      not yet been studied in the human infant brain. This study provides a detailed
      account of the distribution and localization of both pro- and mature-recombinant
      human (rh) forms of BDNF, and of TrkB in the human infant brainstem and
      hippocampus, and qualitatively compares this expression to that seen in the human
      adult. Using commercially available antibodies, we applied immunohistochemistry
      on formalin fixed and paraffin embedded human brain tissue [n=8 for infant, n=6
      for adult], and qualitatively analyzed the expression of proBDNF, rhBDNF and
      TrkB. Amongst the brainstem regions studied, the greatest expression of the
      markers was in the mesencephalic trigeminal of the pons, and in the medulla, the
      inferior olive and arcuate nucleus. The lowest expression was in the substantia
      nigra of the midbrain and pontine locus coeruleus. Compared to adults, all the
      studied markers had a higher expression in the infant brainstem nuclei of the
      hypoglossal, vestibular, dorsal motor nucleus of the vagus, prepositus, cuneate,
      and dorsal raphe. In the hippocampus, only TrkB showed a higher expression in
      infants compared to adults. We conclude that BDNF and TrkB play important roles
      in controlling respiration, movement, balance and feeding in the brainstem and
      that the TrkB receptor is the most age-sensitive component of this system,
      especially in the hippocampus.

PMID- 20673757
TI  - Comparison of the post-embolization effects of tissue-plasminogen activator and
      simvastatin on neurological outcome in a clinically relevant rat model of acute
      ischemic stroke.
AB  - Data has emerged, largely from non-thromboembolic animal models of stroke, that
      suggests that statins, which have efficacy in preventing strokes when given pre
      ischemically, may have a positive effect on stroke even when given post
      ischemically, possibly through pleitropic cerebrovascular effects. The goal of
      this study was to characterize the effects of IV tPA in a clinically relevant
      model of stroke utilizing a vascular occlusion with a freshly formed clot, and
      evaluate the effects of post-ischemic administration of simvastatin on stroke
      outcome in this model. Neurological deficit, clot burden, and lesion volume were
      assessed after treatment with tPA in one experiment, and after treatment with
      simvastatin in another. In the tPA experiment, treatment with 10mg/kg of tPA IV
      (with 20% given as an initial bolus, and 80% given as an infusion over the
      remaining 30 min), starting within an hour after stroke, resulted in significant
      reductions, compared with control animals, in neurological deficit (mean+/-SD
      neuroscores of 21.5+/-21.1 and 30+/-29.3, respectively, p=0.005), clot burden
      (p=0.010) and lesion volume (p=0.049) at 24h. In the simvastatin experiment on
      the other hand, treatment with a 20mg/kg of simvastatin as a single
      intraperitoneal dose within an hour after stroke resulted in no salutary effects
      on neurological deficit, clot burden or lesion volume compared with controls at
      24h. These results suggest that more research needs to be done to fully ascertain
      the therapeutic potential and optimal dosing paradigm of a post-ischemic
      treatment with a statin.

PMID- 20673759
TI  - Ameliorating effects of tropisetron on dopaminergic disruption of prepulse
      inhibition via the alpha(7) nicotinic acetylcholine receptor in Wistar rats.
AB  - Nicotine has ameliorating effects on sensorimotor gating deficits in
      schizophrenia. We have shown that nicotine ameliorated disruption of prepulse
      inhibition (PPI) via the alpha(7) nicotinic acetylcholine receptor (nAChR) in
      Wistar rats. The 5-HT(3) receptor antagonist tropisetron was recently found to be
      an alpha(7) nAChR partial agonist. We initially investigated the effects of
      tropisetron on disruption of PPI induced by phencyclidine (PCP) (2mg/kg) or
      apomorphine (1mg/kg). Tropisetron had no effect on the disruption of PPI induced
      by PCP, but ameliorated the disruption by apomorphine. The ameliorating effect of
      tropisetron was antagonized by methyllycaconitine (2 or 5mg/kg), a partially
      selective alpha(7) nAChR antagonist. Next, to find the action site of
      tropisetron, we examined c-Fos protein expression in the nucleus accumbens (NAc),
      dorsolateral striatum (DLst) and ventral tegmental area (VTA). Tropisetron alone
      did not change the number of c-Fos-positive cells, whereas apomorphine increased
      the number of positive cells in the NAc and DLst. Tropisetron administration
      followed by apomorphine administration decreased the number of positive cells in
      the VTA compared with the apomorphine-alone group. These results suggest that
      tropisetron has an ameliorating effect on the sensorimotor gating deficits via
      the alpha(7) nAChR, and that one possible site of its action is the VTA.

PMID- 20673760
TI  - A BALB/c mouse model shows that liver involvement in dengue disease is immune
      mediated.
AB  - In the present study, BALB/c mice were used to develop a model for the hepatic
      injury associated to dengue infection. Histological analysis after subcutaneous
      inoculation with a low viral dose of dengue-2 virus showed Kupffer cell
      hyperplasia and an increased inflammatory cellular infiltrate next to the bile
      ducts on days 5, 7 and 14 post-inoculation, mainly characterized by the presence
      of mononuclear cells. The liver mRNA transcription level of IL-1beta was highest
      on the 5th day post-infection (p.i.) and decreased by the 21st day, TNF-alpha
      showed a peak of mRNA transcription after 14 days p.i. coinciding with the
      regression of cellular infiltrates and elevated expression of TGF-beta mRNA.
      Serum AST and ALT levels were slightly elevated at 7 and 14 days post-infection.
      Dengue-2 RNA levels were undetectable in the liver on any of the days following
      inoculation. Our observations suggest that, as it is true for humans, the animals
      undergo a transient and slight liver inflammation, probably due to local cytokine
      production and cellular infiltration in the liver.

PMID- 20673761
TI  - Neuropeptide Y modifies the disease course in the R6/2 transgenic model of
      Huntington's disease.
AB  - Huntington's disease (HD) is an inherited neurodegenerative disorder
      characterized by progressive neuronal dysfunction and cell loss, especially
      striatal GABAergic neurons, generating motor, cognitive and affective problems.
      Although the disease-causing gene is known, the exact mechanism by which it
      induces its pathological effect remains unknown, and no cure is currently
      available for this disease. Interestingly, striatal neurons that express
      neuropeptide Y (NPY) are preferentially spared in HD and the number of such cells
      is increased in the striatum of HD patients. Furthermore, neurogenesis in the
      subventricular zone (SVZ) also appears to be up-regulated in HD patients, and
      previously we also demonstrated in wild-type mice that intracerebroventricular
      (ICV) NPY promotes SVZ neurogenesis with migration of the newborn cells towards
      the striatum where they differentiate into GABAergic neurons. Therefore, we
      sought to determine whether NPY could be of therapeutic benefit in a transgenic
      mouse model of HD (R6/2) through an action on SVZ neurogenesis. We found that a
      single ICV injection of NPY in R6/2 mice increased survival time through reduced
      weight loss as well as having a beneficial effect on motor function as evidenced
      by improving rotarod performance and reducing paw-clasping. We also demonstrated
      that the degree of cerebral and striatal atrophy was reduced following such a
      single NPY injection and that whilst the peptide also increased the number of
      BrdU-positive cells in the SVZ (but not in the dentate gyrus) of R6/2 mice, this
      was not sufficient to account for the changes in anatomy and function that we
      found.. These results suggest that NPY may be of some therapeutic interest in
      patients with HD, although further work is needed to ascertain exactly how it
      mediates its beneficial effects.

PMID- 20673762
TI  - Intracerebroventricular delivery of glucocerebrosidase reduces substrates and
      increases lifespan in a mouse model of neuronopathic Gaucher disease.
AB  - Gaucher disease is caused by a deficit in the enzyme glucocerebrosidase. As a
      consequence, degradation of the glycolipids glucosylceramide (GluCer) and
      glucosylsphingosine (GluSph) is impaired, and their subsequent buildup can lead
      to significant pathology and early death. Type 1 Gaucher patients can be treated
      successfully with intravenous replacement enzyme, but this enzyme does not reach
      the CNS and thus does not ameliorate the neurological involvement in types 2 and
      3 Gaucher disease. As one potential approach to treating these latter patients,
      we have evaluated intracerebroventricular (ICV) administration of recombinant
      human glucocerebrosidase (rhGC) in a mouse model of neuronopathic Gaucher
      disease. ICV administration resulted in enzyme distribution throughout the brain
      and alleviated neuropathology in multiple brain regions of this mouse model.
      Treatment also resulted in dose-dependent decreases in GluCer and GluSph and
      significantly extended survival. To evaluate the potential of continuous enzyme
      delivery, a group of animals was treated ICV with an adeno-associated viral
      vector encoding hGC and resulted in a further extension of survival. These data
      suggest that ICV administration of rhGC may represent a potential therapeutic
      approach for type 2/3 Gaucher patients. Preclinical evaluation in larger animals
      will be needed to ascertain the translatability of this approach to the clinic.

PMID- 20673763
TI  - The plasma membrane redox system is impaired by amyloid beta-peptide and in the
      hippocampus and cerebral cortex of 3xTgAD mice.
AB  - Membrane-associated oxidative stress has been implicated in the synaptic
      dysfunction and neuronal degeneration that occurs in Alzheimer's disease (AD),
      but the underlying mechanisms are unknown. Enzymes of the plasma membrane redox
      system (PMRS) provide electrons for energy metabolism and recycling of
      antioxidants. Here, we show that activities of several PMRS enzymes are
      selectively decreased in plasma membranes from the hippocampus and cerebral
      cortex of 3xTgAD mice, an animal model of AD. Our results that indicate the
      decreased PMRS enzyme activities are associated with decreased levels of coenzyme
      Q(10) and increased levels of oxidative stress markers. Neurons overexpressing
      the PMRS enzymes (NQO1 or cytochrome b5 reductase) exhibit increased resistance
      to amyloid beta-peptide (Abeta). If and to what extent Abeta is the cause of the
      impaired PMRS enzymes in the 3xTgAD mice is unknown. Because these mice also
      express mutant tau and presenilin-1, it is possible that one or more of the PMRS
      could be adversely affected by these mutations. Nevertheless, the results of our
      cell culture studies clearly show that exposure of neurons to Abeta1-42 is
      sufficient to impair PMRS enzymes. The impairment of the PMRS in an animal model
      of AD, and the ability of PMRS enzyme activities to protect neurons against Abeta
      toxicity, suggest enhancement PMRS function as a novel approach for protecting
      neurons against oxidative damage in AD and related disorders.

PMID- 20673764
TI  - Allogeneic stem cell transplantation does not improve neurological deficits in
      mucopolysaccharidosis type IIIA mice.
AB  - Mucopolysaccharidosis type IIIA (MPS IIIA) is a neurodegenerative metabolic
      disorder caused by mutations in the N-sulfoglucosamine sulfohydrolase gene with
      resultant accumulation of partially degraded heparan sulfate (HS). Whilst
      allogeneic bone marrow transplantation (BMT) is indicated for several lysosomal
      storage disorders featuring neurodegeneration, its use in MPS III is highly
      controversial. Published evidence suggests that BMT does not improve cognitive
      function in MPS III patients. Despite this, patients continue to be transplanted
      in some centers. We therefore sought to determine the clinical effectiveness of
      BMT in a murine model of MPS IIIA. Pre-symptomatic young adult mice pre
      conditioned with total body irradiation generated complete and stable donor-type
      chimerism. Whilst HS-derived disaccharides were reduced by up to 27% in the brain
      parenchyma, this was insufficient to decrease secondary cholesterol and GM3
      ganglioside storage or permit clinical improvement. These results suggest that
      BMT is ineffective in its unmodified form and should not be considered as a
      treatment for MPS IIIA children.

PMID- 20673765
TI  - Response of the Strongyloides ratti transcriptome to host immunological
      environment.
AB  - The immunological environment experienced by parasitic nematodes varies greatly
      between hosts and is particularly influenced by whether or not a host has been
      previously infected. How a parasitic nematode responds to these different
      environments is poorly understood, but may allow a parasite to ameliorate the
      adverse effects of host immunity on parasite fitness. Here we use a microarray
      approach to identify genes in the parasitic nematode Strongyloides ratti that
      exhibit differential transcription between different rat host immunological
      environments, and between replicate lines of S. ratti selected for either early
      or late reproduction. We hypothesise that such genes may be used by this species
      to cope with and respond to its host environment. Our results showed that,
      despite large phenotypic differences between S. ratti adults from different
      immunological environments, the S. ratti transcriptome exhibited a relatively
      stable pattern of expression. Thus, differential expression amongst treatments
      was limited to a small proportion of transcripts and generally involved only
      modest fold changes. These transcripts included a group of collagen genes up
      regulated in parasites early in an infection, and in immunised host environments,
      which may be related to protection against the damage caused to a parasite by
      host immune responses. We found that later in an infection, a number of genes
      associated with muscle function and repair were up-regulated in immunised host
      environments; these may help parasites maintain their position in the host
      intestine. Differences in transcription between selection lines of S. ratti were
      only observed in immunised hosts and included genes associated with the response
      to the host's immunological environment.

PMID- 20673766
TI  - Failure of Parastrongyloides trichosuri daf-7 to complement a Caenorhabditis
      elegans daf-7 (e1372) mutant: implications for the evolution of parasitism.
AB  - DAF-7 is the ligand of the TGF-beta pathway that, in conjunction with the insulin
      like and guanylyl cyclase pathways, controls entry into dauer development in
      Caenorhabditis elegans. Proposed orthologues of Ce-daf-7 have been identified in
      several species of parasitic nematodes and demonstrate an expression pattern that
      is consistent between parasitic nematode genera but different to that of Ce-daf
      7. This variation in expression pattern is consistent with the current paradigm
      in evolutionary developmental biology: that regulatory rather than functional
      change is the primary source of phenotypic diversity. In this work we
      investigated the proposed orthology of a daf-7 like sequence obtained from
      Parastrongyloides trichosuri, Pt-daf-7, to Ce-daf-7 via transformation rescue of
      a C. elegans daf-7 mutant with Pt-daf-7 coding regions. We also investigated
      further the difference in expression pattern of Pt-daf-7 both by fusing a Pt-daf
      7 promoter to a Ce-daf-7 coding region and to a gfp reporter gene. We found that
      Pt-daf-7 was unable to complement a C. elegans daf-7 mutant, even when reduced to
      the smallest functional TGF-beta unit possible, the ligand domain, and that this
      failure appears to be the result of gene silencing. Furthermore, we show that
      although the Pt-daf-7 promoter is active later in development than the Ce-daf-7
      promoter and most likely active in the correct neurons, a Ce-daf-7 coding region
      under control of a Pt-daf-7 promoter failed to rescue. Together, these results
      suggest that, if the free-living nematode developmental pathways, such as the DAF
      7 TGF- beta pathway, have been co-opted during the evolution of parasitism, this
      co-option has been both at the protein level and in the control of their
      transcription.

PMID- 20673767
TI  - Biological variations of MASP-3 and MAp44, two splice products of the MASP1 gene
      involved in regulation of the complement system.
AB  - The lectin pathway of complement is part of the innate immune system. The
      complement-activating pattern-recognition molecules (for which we suggest the
      abbreviation CAPREMs) mannan-binding lectin (MBL) and the three ficolins (H-, L-
      and M-ficolin) circulate in complexes with MBL-associated serine proteases (MASP
      1, -2 and -3) and two additional proteins (MAp19 and MAp44, also termed sMAP and
      MAP-1, respectively). When MBL or ficolins recognize a microorganism or altered
      self components, activation of the MASPs ensues, leading to the activation of the
      complement system. MASP-1, MASP-3 and MAp44 are all three encoded by the MASP1
      gene. MASP-1 and -3 share five domains (constituting the so-called A-chain), but
      have unique protease domains (B-chains). MAp44 shares the first four domains with
      MASP-1 and MASP-3, followed by 17 unique C-terminal amino acid residues. Thus,
      assays for the protease domain of MASP-3 and for the 17 C-terminal amino acids of
      MAp44 are required to measure these proteins specifically and here we present
      such assays for MASP-3 and MAp44. MASP-3 was captured with a monoclonal antibody
      (5F5) reacting with a common domain of the three proteins (CCP1) and the assay
      was developed with a monoclonal antibody (38.12.3) specific for the C-terminal
      part of the MASP-3 protease domain. MAp44 was captured with a monoclonal antibody
      (2D5) reacting with the C-terminus of MAp44 followed by assay development with a
      monoclonal anti-CCP1 antibody (4H2). Using Superose 6 gel permeation
      chromatography of serum, MASP-3 and MAp44 were found in complexes, which eluted
      in positions corresponding to 600-800 kDa and 500-700 kDa, respectively. The
      level of MASP-3 in donor sera (N=200) was log-normally distributed with a median
      value of 5.0 MUg/ml (range: 1.8-10.6 MUg/ml), and the corresponding value for
      MAp44, also log-normally distributed, was 1.7 MUg/ml (range: 0.8-3.2 MUg/ml). For
      MASP-3, the inter-assay coefficients of variation of low, intermediate and high
      level internal controls were 4.9%, 6.9% and 3.9% (N=12). For MAp44, the
      corresponding inter-assay CVs were 7.6%, 6.2%, and 7.0% (N=12). MASP-3 levels
      were low at birth and reached adult levels within the first 6 months, whereas
      MAp44 levels fell slightly during the first 6 months. Concomitant with the acute
      phase response in patients undergoing major surgery, levels of both proteins fell
      slightly over 1-2 days, but whereas MASP-3 recovered to baseline values over
      another 2 days, MAp44 only reached baseline values at around day 30. Thus,
      neither of the two proteins behaves as a classical acute phase protein.

PMID- 20673768
TI  - Effects of infection with Nosema pyrausta on survival and development of
      offspring of laboratory selected Bt-resistant and Bt-susceptible European corn
      borers.
AB  - Infection with Nosema pyrausta Paillot lengthens developmental period of Bt
      susceptible Ostrinia nubilalis (Hubner) to a similar extent as feeding on Cry1Ab
      incorporated diet in Cry1Ab-resistant O. nubilalis, and these two factors
      combined lengthen developmental period further than either alone. Resistant O.
      nubilalis mating with infected susceptible, or infected resistant partners would
      produce partially- and fully-resistant offspring, respectively, infected with N.
      pyrausta. To investigate the impacts on the progeny of such matings, test crosses
      were set up to produce partially- and fully Cry1Ab-resistant O. nubilalis
      offspring transovarially infected and not infected with N. pyrausta, which were
      exposed to Cry1Ab toxin at doses of 0, 3, or 30ng/cm(2) for 7days. Transovarial
      infection with N. pyrausta significantly decreased 7day survival of partially and
      fully-resistant O. nubilalis feeding on 30ng/cm(2) Cry1Ab. In addition, N.
      pyrausta infection delayed larval development (as measured by weight) of
      partially- and fully-resistant O. nubilalis feeding on 3 and 30ng/cm(2) Cry1Ab.
      Impacts of natural enemies on target pests may have the potential to impact
      evolution of resistance. N pyrausta-infected O. nubilalis are more strongly
      affected by feeding on Bt, and would be less likely to survive to adulthood to
      pass on resistance to the next generation. This indigenous microsporidium may
      work to delay evolution of resistance in O. nubilalis by lowering their ability
      to survive on Bt.

PMID- 20673769
TI  - Endothelial progenitor cells: quo vadis?
AB  - The term endothelial progenitor cell (EPC) was coined to refer to circulating
      cells that displayed the ability to display cell surface antigens similar to
      endothelial cells in vitro, to circulate and lodge in areas of ischemia or
      vascular injury, and to facilitate the repair of damaged blood vessels or augment
      development of new vessels as needed by a tissue. More than 10 years after the
      first report, the term EPC is used to refer to a host of circulating cells that
      display some or all of the qualities indicated above, however, essentially all of
      the cells are now known to be members of the hematopoietic lineage. The exception
      is a rare viable circulating endothelial cell with clonal proliferative potential
      that displays the ability to spontaneously form inosculating human blood vessels
      upon implantation into immunodeficient murine host tissues. This paper will
      review the current lineage relationships among all the cells called EPC and will
      propose that the term EPC be retired and that each of the circulating cell
      subsets be referred to according to the terms already existent for each subset.
      This article is part of a special issue entitled, "Cardiovascular Stem Cells
      Revisited".

PMID- 20673770
TI  - Identification of right heart-enriched genes in a murine model of chronic outflow
      tract obstruction.
AB  - The right ventricle (RV) differs in several aspects from the left ventricle (LV)
      including its embryonic origin, physiological role and anatomical design. In
      contrast to LV hypertrophy, little is known about the molecular circuits, which
      are activated upon RV hypertrophy (RVH). We established a highly reproducible
      model of RVH in mice using pulmonary artery clipping (PAC), which avoids
      detrimental RV pressure overload and thus allows long-term survival of operated
      mice. Magnetic resonance imaging revealed pathognomonic changes with striking
      similarities to human congenital heart disease- or pulmonary arterial
      hypertension-patients. Comparative, microarray based transcriptome analysis of
      right- and left-ventricular remodeling identified distinct transcriptional
      responses to pressure-induced hypertrophy of either ventricle, which were mainly
      characterized by stronger transcriptional responses of the RV compared to the LV
      myocardium. Hierarchic cluster analysis revealed a RV- and LV-specific pattern of
      gene activity after induction of hypertrophy, however, we did not find evidence
      for qualitatively distinct regulatory pathways in RV compared to LV. Data mining
      of nearly three thousand RV-enriched genes under PAC disclosed novel potential
      (co)-regulators of long-term RV remodeling and hypertrophy. We reason that
      specific inhibitory mechanisms in RV restrict excessive myocardial hypertrophy
      and thereby contribute to its vulnerability to pressure overload.

PMID- 20673771
TI  - Parameter study of simplified dragonfly airfoil geometry at Reynolds number of
      6000.
AB  - Aerodynamic study of a simplified Dragonfly airfoil in gliding flight at Reynolds
      numbers below 10,000 is motivated by both pure scientific interest and
      technological applications. At these Reynolds numbers, the natural insect flight
      could provide inspiration for technology development of Micro UAV's and more.
      Insect wings are typically characterized by corrugated airfoils. The present
      study follows a fundamental flow physics study (Levy and Seifert, 2009), that
      revealed the importance of flow separation from the first corrugation, the roll
      up of the separated shear layer to discrete vortices and their role in promoting
      flow reattachment to the aft arc, as the leading mechanism enabling high-lift,
      low drag performance of the Dragonfly gliding flight. This paper describes the
      effect of systematic airfoil geometry variations on the aerodynamic properties of
      a simplified Dragonfly airfoil at Reynolds number of 6000. The parameter study
      includes a detailed analysis of small variations of the nominal geometry, such as
      corrugation placement or height, rear arc and trailing edge shape. Numerical
      simulations using the 2D laminar Navier-Stokes equations revealed that the flow
      accelerating over the first corrugation slope is followed by an unsteady pressure
      recovery, combined with vortex shedding. The latter allows the reattachment of
      the flow over the rear arc. Also, the drag values are directly linked to the
      vortices' magnitude. This parametric study shows that geometric variations which
      reduce the vortices' amplitude, as reduction of the rear cavity depth or the
      reduction of the rear arc and trailing edge curvature, will reduce the drag
      values. Other changes will extend the flow reattachment over the rear arc for a
      larger mean lift coefficients range; such as the negative deflection of the
      forward flat plate. These changes consequently reduce the drag values at higher
      mean lift coefficients. The detailed geometry study enabled the definition of a
      corrugated airfoil geometry with enhanced aerodynamic properties, such as range
      and endurance factors, as compared to the nominal airfoil studied in the
      literature.

PMID- 20673772
TI  - On the stability of metabolic cycles.
AB  - We investigate the stability properties of two different classes of metabolic
      cycles using a combination of analytical and computational methods. Using
      principles from structural kinetic modeling (SKM), we show that the stability of
      metabolic networks with certain structural regularities can be studied using a
      combination of analytical and computational techniques. We then apply these
      techniques to a class of single input, single output metabolic cycles, and find
      that the cycles are stable under all conditions tested. Next, we extend our
      analysis to a small autocatalytic cycle, and determine parameter regimes within
      which the cycle is very likely to be stable. We demonstrate that analytical
      methods can be used to understand the relationship between kinetic parameters and
      stability, and that results from these analytical methods can be confirmed with
      computational experiments. In addition, our results suggest that elevated
      metabolite concentrations and certain crucial saturation parameters can strongly
      affect the stability of the entire metabolic cycle. We discuss our results in
      light of the possibility that evolutionary forces may select for metabolic
      network topologies with a high intrinsic probability of being stable.
      Furthermore, our conclusions support the hypothesis that certain types of
      metabolic cycles may have played a role in the development of primitive
      metabolism despite the absence of regulatory mechanisms.

PMID- 20673773
TI  - Gene feature interference deconvolution.
AB  - High-throughput microarray technologies measure the abundance of thousands of
      mRNA targets simultaneously. Due to the usual disparity between a few available
      samples (from limited conditions or time course points) and many gene expression
      values (entire genomes), a complex high-dimensional genomic system has to be
      analyzed, for instance by reverse engineering methods. The latter aim to
      reconstruct gene networks from experimentally observed expression changes caused
      by various kinds of perturbations. In particular, elucidating regulatory paths
      and assessing their reliability across replicates are central topics in this
      article. The reconstruction problem requires efficiency and accuracy from
      numerical optimization algorithms and statistical inference techniques. To this
      end, we focus on methods but also on the available experimental information
      produced in technical replicates. We propose a model-based approach based on a
      few steps. First, feature selection is performed by a projective method aimed to
      combine the gene measurements observed across replicates. Second, a quite
      heuristic sieving strategy is pursued to bypass the usual recourse to averaging.
      Third, the impact of dimensionality reduction on the biological system under
      study is evaluated. Evidence is obtained from the application of our approach to
      microarray time course experimental replicated data, and suggests that gene
      features, once identified, can be used for stabilization purposes relatively to
      the replicate variability. Both quantitative representation and qualitative
      assessment of the observed gene feature interference are reported in order to
      decipher specific gene regulatory map and the pathway-associated dynamics.

PMID- 20673774
TI  - Structure-based drug discovery and protein targets in the CNS.
AB  - Structure-based methods are having an increasing role and impact in drug
      discovery. The crystal structures of an increasing number of therapeutic targets
      are becoming available. These structures can transform our understanding of how
      these proteins perform their biological function and often provide insights into
      the molecular basis of disease. In addition, the structures can help the
      discovery process. Methods such as virtual screening and experimental fragment
      screening can provide starting hit compounds for a discovery project. Crystal
      structures of compounds bound to the protein can direct or guide the medicinal
      chemistry optimisation to improve drug-like properties - not only providing ideas
      on how to improve binding affinity or selectivity, but also showing where the
      compound can be modified in attempting to modulate physico-chemical properties
      and biological efficacy. The majority of drug discovery projects against globular
      protein targets now use these methods at some stage. This review provides a
      summary of the range of structure-based drug discovery methods that are in use
      and surveys the suitability of the methods for targets currently identified for
      CNS drugs. Until recently, structure-based discovery was difficult or unknown for
      these targets. The recent determination of the structures of a number of GPCR
      proteins, together with the steady increase in structures for other membrane
      proteins, is opening up the possibility for these structure-based methods to find
      increased use in drug discovery for CNS diseases and conditions.

PMID- 20673775
TI  - Size-dependent sex change can be the ESS without any size advantage of
      reproduction when mortality is size-dependent.
AB  - Almost all models of sex change evolution assume that reproductive rate increases
      with body size. However, size-dependent sex changing plants often show size
      independent reproductive success, presumably due to pollen limitation. Can the
      observed size-dependent sex change pattern be the ESS in this case? To answer
      this question, we analyze a game model of size-dependent sex expression in
      plants. We assume: (1) reproductive rate is perfectly independent of size; (2)
      mortality decreases with size in the same way for both sexes; (3) growth rates
      decrease at maturity, more for females than males. We show that the ESS is size
      dependent sex expression: small individuals are vegetative, intermediate
      individuals are male, and large individuals are female. These results demonstrate
      that mortality is important in size-dependent sex allocation even when mortality
      rate is independent of sex. They also offer an explanation of why we see
      populations in poor environments to have sex ratios more biased toward the first
      sex relative to high quality environments.

PMID- 20673776
TI  - Inhibitory tagging in visual search: only in difficult search are items tagged
      individually.
AB  - Several theories and models of visual search assume that inhibitory tagging of
      items is used to improve the efficiency of the search process, by discouraging
      revisits of previously inspected and rejected items. Therefore, search should
      become less efficient when the search display consists of moving items. In four
      experiments this hypothesis was tested. In the first two experiments there was no
      difference between search amongst static and moving items even though motion
      conditions were blocked (Experiment 1), or displays contained up to 36 items
      (Experiment 2). However, in Experiments 3 and 4, where the items used in the
      search display forced the participants to keep track of individual items
      performance dropped when the items moved. Visual search showed a remarkable
      robustness against motion, which current theories and models of visual search
      have difficulties to describe. Taken together, the results reported here indicate
      that there is a difference between the processes used in easier search and those
      used in search where items need to be individuated. A framework encompassing
      these results is proposed.

PMID- 20673777
TI  - Anisotropies in the perceived spatial displacement of motion-defined contours:
      opposite biases in the upper-left and lower-right visual quadrants.
AB  - In a recent study (Fan, Z., & Harris, J. (2008). Perceived spatial displacement
      of motion-defined contours in peripheral vision. Vision Research, 48(28), 2793
      2804), we demonstrated that virtual contours defined by two regions of dots
      moving in opposite directions were displaced perceptually in the direction of
      motion of the dots in the more eccentric region when the contours were viewed in
      the right visual field. Here, we show that the magnitude and/or direction of
      these displacements varies in different quadrants of the visual field. When
      contours were presented in the lower visual field, the direction of perceived
      contour displacement was consistent with that when both contours were presented
      in the right visual field. However, this illusory motion-induced spatial
      displacement disappeared when both contours were presented in the upper visual
      field. Also, perceived contour displacement in the direction of the more
      eccentric dots was larger in the right than in the left visual field, perhaps
      because of a hemispheric asymmetry in attentional allocation. Quadrant-based
      analyses suggest that the pattern of results arises from opposite directions of
      perceived contour displacement in the upper-left and lower-right visual
      quadrants, which depend on the relative strengths of two effects: a greater
      sensitivity to centripetal motion, and an asymmetry in the allocation of spatial
      attention.

PMID- 20673778
TI  - Social orienting: reflexive versus voluntary control.
AB  - Many studies have shown that the direction of gaze of a face covertly facilitates
      the response to a target presented in the matching direction. In this study we
      seek to determine whether there exist separate reflexive and voluntary forms of
      such covert social orienting and how they interact with each other. We measured
      the effect of the predictive value of a gaze cue on manual choice reaction times.
      When the predictive value of the gaze cue was zero, a facilitatory cueing effect
      was still observed which peaked at a cue onset to target onset delay (CTD) of
      150ms and largely diminished beyond a CTD of 500ms. When the gaze cue was 100%
      predictive of the future location of the target, at CTDs greater than 200, the
      predictive cue resulted in a significantly greater facilitation of response than
      occurred with a non-predictive cue. These results suggest that given enough time
      (about 200ms), the social cue is interpreted and a willful or voluntary spatially
      specific social cueing effect occurs. In addition, we found that a predictive cue
      resulted in a significant slowing of the observer's responses up to a CTD of
      200ms. These findings show that, similar to non-social spatial orienting, there
      appear to be two forms of social orienting including a reflexive component and
      voluntary component. We suggest a model of social orienting in which the
      voluntary social orienting system modulates tonic inhibition of the reflexive
      social orienting system.

PMID- 20673779
TI  - Local cerebral glucose utilization in rats exposed to an enriched environment: a
      comparison to impoverishment.
AB  - Environmental enrichment and environmental impoverishment have been shown to
      differentially alter brain function. Here, we investigate the effects of
      enrichment vs. impoverishment on cerebral use of glucose in rodents. Rats were
      housed from postnatal day 28 to day 58 in either a socially and environmentally
      enriched environment or an impoverished environment devoid of other rats or
      environmental stimuli. Locomotor activity was measured at the end of the
      enrichment/impoverishment period. Following the duration of the exposure to these
      environments, cerebral metabolic rate of glucose utilization was determined using
      quantitative 2-[(14)C]deoxyglucose autoradiography in 37 brain regions in the
      cerebral cortex, forebrain, brain stem and thalamus. There were no differences in
      locomotor activity between the conditions. The nucleus accumbens core and shell
      had significantly higher rates of glucose utilization in enriched compared to
      impoverished animals. These data suggest that environment has a significant
      effect on brain function which may help to explain the beneficial and protective
      effects of enrichment against drug abuse and addiction.

PMID- 20673781
TI  - Endogenous hyperinsulinaemia in insulinoma patients is not associated with
      changes in beta-cell area and turnover in the tumor-adjacent pancreas.
AB  - INTRODUCTION: Insulin therapy has been suggested to preserve beta-cell mass in
      patients with diabetes through the mechanisms of beta-cell rest as well as direct
      effects on beta-cell proliferation. However, data about the effects of
      hyperinsulinism on beta-cell mass and turnover in humans are sparse. PATIENTS AND
      METHODS: Pancreatic tissue specimens from five patients with pancreatic
      insulinomas and ten non-diabetic control subjects were examined. Pancreatic
      sections were stained for insulin, Ki67 (replication) and TUNEL (apoptosis), and
      quantitative morphometric analyses were performed. RESULTS: Fractional beta-cell
      area was 1.11%+/-0.67% in the tumor-free pancreatic tissue of the insulinoma
      patients and 0.78%+/-0.26% in the control group (p=0.19). There also were no
      differences in islet size (p=0.62) or beta-cell nuclear diameter (p=0.20). Beta
      cell replication and apoptosis were infrequently detected, without any measurable
      differences between the groups. There were also no differences in percentage of
      duct cells expressing insulin (p=0.47), a surrogate marker for islet neogenesis.
      CONCLUSIONS: Beta-cell area and turnover are not significantly altered in the
      proximity of intra-pancreatic insulinomas. Future in vivo studies, ideally
      employing larger animal models, are warranted to further evaluate the impact of
      exogenous insulin on beta-cell turnover.

PMID- 20673782
TI  - Adjunctive lamotrigine therapy for patients with bipolar II depression partially
      responsive to mood stabilizers.
AB  - This naturalistic study explored long-term effectiveness of adjunctive
      lamotrigine therapy for bipolar II depression. We analyzed prospective data from
      109 lamotrigine-treated outpatients with bipolar II depression inadequately
      responsive to mood stabilizers. Lamotrigine was added to prior treatment in a
      naturalistic fashion. Changes in depression severity were prospectively monitored
      for up to 52 weeks using a prospective mood chart and the Clinical Global
      Impressions-Bipolar Version-Severity (CGI-BP-S). Time to lamotrigine
      discontinuation during 52-week period was calculated using the Kaplan-Meier
      estimate. A significant reduction in the CGI-BP-S depression score was observed
      between baseline and week 52 with a large effect size. The discontinuation rates
      were 44.0% and 50.5% for the total sample and 14.3% and 22.9% for responders at
      24 weeks and 52 weeks, respectively. A higher number of prior hospitalizations
      for depression and a history of attempted suicide were associated with poor
      response to adjunctive lamotrigine treatment. Sustained benefits of an open-label
      lamotrigine add-on were indicated in patients with bipolar II depression.
      Adjunctive usage of lamotrigine was safe and generally well-tolerated. The
      potential benefit of adjunctive lamotrigine treatment was suggested in patients
      with bipolar II disorder suffering from depressive symptoms. Large-scale
      controlled studies are needed to confirm the effectiveness of adjunctive
      lamotrigine therapy for bipolar II depression.

PMID- 20673780
TI  - Hijacking the T-cell communication network by the human T-cell leukemia/lymphoma
      virus type 1 (HTLV-1) p12 and p8 proteins.
AB  - The non-structural proteins encoded by the orf-I, II, III, and IV genes of the
      human T-cell leukemia/lymphoma virus type 1 (HTLV-1) genome, are critical for the
      modulation of cellular gene expression and T-cell proliferation, the escape from
      cytotoxic T-cells and natural killer cells, and virus expression. In here, we
      review the main functions of the HTLV-1 orf-I products. The 12kDa product from
      orf-I (p12) is proteolytically cleaved within the endoplasmic reticulum (ER) to
      generate the 8kDa protein (p8). At the steady state, both proteins are expressed
      at similar levels in transfected T-cells. The p12 protein remains in the ER and
      cis-Golgi, whereas the p8 protein traffics to the cell surface and is recruited
      to the immunological synapse. The p12 and the p8 proteins have seemingly opposite
      effects on T-cells; the ER resident p12, modulates T-cell activation and
      proliferation, whereas p8 induces T-cell anergy. The p8 protein also increases
      the formation of cellular conduits, is transferred to neighboring T-cells, and
      increases virus transmission. The requirement for HTLV-1 infectivity of orf-I is
      demonstrated by the loss of virus infectivity in macaques exposed to an
      engineered virus, whereby expression of orf-I was ablated. Altogether the current
      knowledge demonstrates that the concerted activity of p8 and p12 is essential for
      the persistence of virus infected cells in the host.

PMID- 20673783
TI  - A cognitive neuropsychological model of antidepressant drug action.
AB  - The psychological mechanisms by which antidepressant drugs act to improve mood
      remain underspecified. In this paper we consider the evidence to suggest that
      early changes in emotional processing underlie subsequent mood improvement
      following antidepressant treatment. Negative biases in information processing are
      consistently found in depression, and we argue that primary mode of action of
      antidepressant drugs may be to remediate these biases providing a more positive
      social environment in which the patient can relearn emotional associations
      fostering later improvement in mood. Evidence from behavioural and functional
      magnetic resonance imaging studies supports this hypothesis. Experimental
      medicine models developed under this premise have the potential to screen for new
      treatments, to predict individual treatment response and to consider the effects
      of pharmacological vs psychological treatments.

PMID- 20673784
TI  - Reduced prefrontal cortex activation during divergent thinking in schizophrenia:
      a multi-channel NIRS study.
AB  - Relationships between deficits in verbal fluency and poor social functioning have
      been revealed in patients with schizophrenia. In previous studies, we
      demonstrated that deficits in idea fluency, which is ranked as a more complex
      type of verbal fluency and reflects divergent thinking ability, were more closely
      related to social dysfunction than deficits in simple word fluency. Although
      functional neuroimaging studies have provided detailed data regarding prefrontal
      dysfunction during word fluency tasks, the regions that relate to deficits in
      fluency of ideas and thoughts have not yet been clarified in schizophrenia
      patients. The purpose of the present study was to identify the prefrontal sub
      regions responsible for deficits in idea fluency using near-infrared spectroscopy
      (NIRS), which is more practical than other imaging methods, and to investigate
      the relationships between lesions and idea fluency deficits and social
      dysfunction in patients with schizophrenia. Eighteen outpatients with
      schizophrenia and 16 healthy subjects were recruited for this case-controlled
      study. Using 24-channel NIRS, we measured changes in hemoglobin concentration in
      the prefrontal cortical surface area during idea and letter fluency tests. The
      analyses revealed that schizophrenia patients generally exhibited a smaller
      increase in the concentration of oxyhemoglobin in the frontopolar region than the
      controls during both the tests. However, the areas in which reduced activations
      were demonstrated in the patients differed remarkably between the idea and letter
      fluency tests: reduced activations were observed in the ventral region during the
      former test and in the dorsal region of the frontopolar cortex during the latter
      test. The reduced activations in each sub-region appeared to affect the related
      cognitive impairment, since the patients showed significant poorer performances
      than the controls on both the tests. Moreover, hypoactivity during idea fluency
      was significantly correlated with poor social functioning as assessed using the
      Global Assessment of Functioning (GAF) in the patient group. The results of the
      present study suggest that the ventral region within the frontopolar cortex is
      responsible for divergent thinking, which is associated with poor social
      functioning in patients with schizophrenia.

PMID- 20673785
TI  - Impact of two toothpastes on repairing enamel erosion produced by a soft drink:
      an AFM in vitro study.
AB  - OBJECTIVES: The aim of the present in vitro study was the evaluation of two
      toothpastes (Sensodyne Pronamel and Biorepair Plus on repairing enamel erosion
      produced by a soft drink (Coca Cola), using Atomic Force Microscopy (AFM).
      METHODS: Fifty extracted human central incisors free of caries were selected and
      divided in a treatment and a control half; they were kept in artificial saliva
      during whole experimentation. The treatment halves were divided into five groups;
      group 1: demineralization with soft drink; group 2: demineralization with soft
      drink + Pronamel; group 3: demineralization with soft drink + Biorepair Plus;
      group 4: intact enamel + Pronamel; group 5: intact enamel + Biorepair Plus.
      Specimen demineralization was carried on in 4 intervals of 2 min. In groups 2, 3,
      4, and 5 the toothpastes were applied for 3 min at 0, 8, 24 and 36 h. The surface
      of each specimen was imaged by AFM and R(rms), root-mean-square roughness, and
      Maximum Depth of the cavities were registered. RESULTS: Amongst treatment
      specimens of groups 1, 2, and 3 a statistically significant difference (P<0.01)
      in R(rms) and Maximum Depth values was registered: the toothpastes reduced enamel
      demineralization. No statistical differences in R(rms) values were registered
      between the two toothpastes. CONCLUSIONS: The toothpastes tested (Pronamel and
      BioRepair Plus) offer a degree of protection from erosive drinks.

PMID- 20673786
TI  - Zebrafish Nanos interacts with and regulates the phosphorylation of Mylz2.
AB  - Nanos genes were required for differentiation of the anterior-posterior body axis
      in the Drosophila embryo. In addition to this somatic function, the nanos protein
      plays critical roles in the migration and survival of PGCs in vertebrates and
      invertebrates, but the regulating mechanisms of Nanos is largely undefined during
      the embyro development. In this study, we report a novel interaction between
      zebrafish Nanos and myosin light chain II (Mylz2). This stable complex, which is
      formed through the RNA-binding zinc finger domain and fourteen amino acids at the
      C-terminus of Nanos, was confirmed by GST pull-down and co-immunoprecipitation.
      Both of these two parts are required for the interaction with Mylz2, but ninety
      one amio acids at N-terminus of Nanos are not required. Using a phospho-myosin
      light chain 2 (Ser19) antibody, we demonstrate that Nanos downregulates the
      phosphorylation of the Mylz2 by cotransfecting PRK-FLAG-Na and PRK-HA-My Mylz2 in
      93T cell. We discuss the biological roles of the interaction between Nanos and
      Mylz2 and the Nanos regulating phosphorylation of the Mylz2 in PGCs.

PMID- 20673787
TI  - Timing and voluntary suppression of facial mimicry to smiling faces in a Go/NoGo
      task--an EMG study.
AB  - Results obtained with a novel emotional Go/NoGo task allowing the investigation
      of facial mimicry (FM) during the production and inhibition of voluntary smiles
      are discussed. Healthy participants were asked to smile rapidly to happy faces
      and maintain a neutral expression to neutral faces, or the reverse. Replicating
      and extending previous results, happy faces induced FM, as shown by stronger and
      faster zygomatic activation to happy than neutral faces in Go trials, and a
      greater number of false alarms to happy faces in NoGo trials. Facial mimicry
      effects remained present during participants' active inhibition of facial
      movement. Latencies of FM were short with 126-250 ms in Go trials, and 251-375 ms
      in NoGo trials. The utility of the Go/NoGo task, which allows the assessment of
      response inhibition in the domain of facial expression by installing strong
      prepotent motor responses via short stimulus presentation times and a great
      number of Go trials, is discussed.

PMID- 20673788
TI  - Androgens stimulate telomerase expression, activity and phosphorylation in
      ovarian adenocarcinoma cells.
AB  - Androgens have been implicated in increasing ovarian cancer risk. Most ovarian
      cancer cells have high telomerase activity which is effective in inducing ovarian
      carcinogenesis. The purpose of this study was to investigate the effects of
      testosterone and androstenedione on the viability of an ovarian adenocarcinoma
      cell line, the activity and expression of telomerase, and the phosphorylation
      status of its catalytic subunit in these cells. Results showed that androgens
      significantly increased the viability of ovarian cancer cells and that these
      hormones induced the expression, activity and phosphorylation of telomerase. This
      upregulation was blocked by phosphatidylinositol 3-kinase pathway inhibitors.
      These findings might have implications for understanding the role of androgens in
      ovarian carcinogenesis.

PMID- 20673789
TI  - Characterization of nestin expression in the spinal cord of GFP transgenic mice
      after peripheral nerve injury.
AB  - Many studies have shown that activation and increase in the number of astrocytes
      and microglia in the spinal cord participate in the initiation and maintenance of
      neuropathic pain, but little attention has been paid to the responses of neural
      progenitor cells to peripheral nerve injury. Nestin, a class VI intermediate
      filament protein, is expressed both in neuronal and glial progenitors as well as
      in their common precursors; and nestin-positive cells appear in the brain and
      spinal cord following various forms of damage to these regions. To clarify the
      responses of neural progenitor cells to nerve injury, we applied L5 spinal nerve
      transection (L5-SNT) to nestin-promoter GFP (pNestin-GFP) transgenic mice to
      narrow the target to them. While pNestin-GFP expression was strongly retained in
      the ependyma lining the central canal of the transgenic spinal cord even in
      adulthood, it was markedly reduced in the dorsal horn during postnatal
      development by day 7. Increases in pNestin-GFP expression and labeling by the
      proliferation marker 5-bromodeoxyuridine were broadly found in the dorsal horn of
      adult mice on day 3 after L5-SNT. On the other hand, the activation and increase
      in number of microglia and astrocytes are restricted to the superficial layer of
      the dorsal horn, the central terminal of injured primary afferent fibers.
      Purinergic P2X agonist alpha, beta-MeATP increased [Ca(2+)]i in nestin-positive
      cells in the superficial layer ipsilateral to nerve injury and P2 receptor
      antagonists suramin and pyridoxalphosphate-6-azophenyl-2,4-disulphonic acid
      (PPADS) blocked the expression and elongation of pNestin-GFP fibers in the slice
      culture of the spinal cord. These results with pNestin-GFP transgenic mice
      demonstrate that nestin-positive cells proliferate in the dorsal horn in response
      to peripheral nerve injury and suggest that ATP may contribute to the expression
      of nestin and activation of neural progenitor cells after nerve injury.

PMID- 20673790
TI  - Performance of a repetitive task by aged rats leads to median neuropathy and
      spinal cord inflammation with associated sensorimotor declines.
AB  - Epidemiological studies have demonstrated a relationship between advancing age
      and susceptibility to risk factors for median neuropathies and musculoskeletal
      disorders. In this study, we determined if performance of a voluntary reaching
      task by aged rats induced sensorimotor declines, median nerve dysfunction and
      increased inflammatory cytokines in peripheral nerves, muscle and spinal cord
      neurons. Aged (14 mon) rats were trained for 15 min/day for 4 weeks to learn a
      high repetition, low force (HRLF) task (19 reaches/min; 15% maximum pulling
      force). Aged task rats performed the task for 2 h/day, 3 days/wk, for 12 weeks
      (until they were 18 mon of age). No behavioral changes were detected in normal
      controls (NC) or food-restricted controls (FR C) as they aged. However, grip
      strength declined in HRLF rats in weeks 6-12 (P<0.01 each) and 12-week trained
      only rats (TR; P<0.05), compared to NC. Mechanical hypersensitivity was present
      in weeks 9 and 12 HRLF reach limb forepaws (P<0.01 and P<0.05, respectively), and
      12-week HRLF support limb forepaws (P<0.01) and hindpaws (P=0.03), compared to
      NC. By week 12, median nerve conduction velocity declined 23%, bilaterally, in
      HRLF (P<0.001 each), and 13% in TR (P<0.05), compared to NC. Tumor necrosis
      factor alpha (TNFalpha) increased in 12-week HRLF muscle (P=0.005), median nerve
      (P<0.01), and neurons in superficial lamina of HRLF cervical spinal cords
      (P<0.01), compared to NC. interleukin 1 beta (IL1beta) also increased in
      superficial lamina neurons (P<0.01). Loss of grip strength was correlated with
      median nerve conduction slowing (r=0.70) as well as increased nerve and muscle
      TNFalpha (r=-0.38 and r=-0.41, respectively); decrease in forepaw withdrawal
      thresholds was correlated with median nerve conduction slowing (r=0.81),
      increased nerve TNFalpha (r=-0.59), and increased TNFalpha and IL1beta in neurons
      in spinal cord dorsal horns (r=-0.52 and r=-0.47, respectively). Thus, aged rats
      performing a repetitive task exhibited sensorimotor declines that were associated
      with decreased median nerve conduction, and increased pro-inflammatory cytokines
      in the median nerve and cervical spinal cord neurons.

PMID- 20673791
TI  - Movement rehabilitation after spinal cord injuries: emerging concepts and future
      directions.
AB  - Considerable inroads are being made into developing new treatments for spinal
      cord injury (SCI) which aim to facilitate functional recovery, including
      locomotion. Research on rehabilitative strategies following SCI using animal
      models has demonstrated that regaining and maintaining motor function, such as
      standing or stepping, is governed by principles of skill acquisition. Mechanisms
      key to learning motor tasks, including retention and transfer of skill, feedback
      and conditions of practice, all have examples in the SCI animal literature,
      although the importance of many concepts may often be overlooked. Combinatorial
      strategies which include physical rehabilitation are beginning to yield promising
      results. However, the effects of molecular-cellular interventions including
      chondroitinaseABC, anti-NogoA, foetal stem cell transplantation, etc., are still
      poorly understood with reference to the changes made to spinal plasticity by
      training and exercise. Studies that investigate the interplay between
      rehabilitation and other treatments have had mixed results; it appears likely
      that precise timings of different interventions will help to maximize recovery of
      function. Understanding how the time-course of injury and different
      rehabilitative and treatment modalities might factor into spinal plasticity will
      be critical in future therapeutic interventions.

PMID- 20673792
TI  - Effect of short-term lead exposure on PTZ-induced seizure threshold in mice.
AB  - This study was designed to determine the effect of different concentrations of
      lead acetate on seizure threshold. Balb?c male mice were randomly divided into
      one control group provided with tap water and four experimental groups received
      lead acetate in drinking water for 30 days at concentrations of 50, 100, 200 and
      400 ppm. Intravenous infusion of pentylenetetrazole (PTZ) was used to induce
      seizure signs and elapsed time was recorded to calculate the threshold dose. At
      the end of the experiments blood samples were taken to measure the blood lead
      level. Threshold doses of PTZ were significantly lower in 100, 200 and 400 ppm
      lead exposed groups for the induction of all seizure stages. Blood lead level
      increased in all experimental groups compared to control dose-dependently.
      Considering the lack of any response induced by 50 ppm concentration of lead, it
      may be concluded that 100 ppm of lead was the minimal effective dose. Therefore,
      lead acetate at a concentration of 100 ppm that produces similar blood level in
      human populations approves the enhancement of convulsive attack risk. Considering
      the effect of low levels of lead in the reduction of seizure threshold, more
      investigations should be carried out to clarify the exact mechanisms.

PMID- 20673793
TI  - Antidepressant-like effects of the active acidic polysaccharide portion of
      ginseng in mice.
AB  - AIM OF THE STUDY: The biological of activity of Panax ginseng C.A. Meyer
      (ginseng) is complex but some of its known effects are related to affective and
      anxiety disorders, including the enhancement of neuroprotection, cellular
      resilience and plasticity. Whereas such effects suggest that ginseng might have
      antidepressant activity, previous studies show incongruent results. The sources
      of contrasting results might be many but one possibility is the utilization of
      different ginseng preparations in different studies. The current study was
      therefore designed to examine the effects of a very specific component of ginseng
      extract, the acidic polysaccharide portion of the plant (WGPA), containing
      arabinogalactan, type-I rhamnogalacturonan (RG-I)- and homogalacturonan (HG)-rich
      pectins. MATERIALS AND METHODS: WGPA was extracted from ginseng roots and
      administered orally to mice at 100 mg/kg and 200 mg/kg doses. WGPA was
      administered chronically, once daily for 1 week before the start of experiments
      and throughout the behavioral tests battery. Mice were tested for spontaneous
      activity, social interactions, anxiety-like behavior in the elevated plus-maze
      (EPM) and despair-like behavior in the forced swim test (FST). RESULTS: WGPA had
      no effects on spontaneous activity or behavior in the EPM. In contrast, 100 mg/kg
      (but not the 200 mg/kg) WGPA significantly reduced immobility time in the FST and
      both doses significantly increased social interactions and decreased aggressive
      behaviors in mice. CONCLUSION: These results suggest that chronic WGPA treatment
      might have antidepressant-like effects that are unrelated to generalized
      behavioral changes. The results are discussed in the context of the known ability
      of the active ingredients of ginseng to increase neuroprotection, similar to many
      of the current antidepressant and mood stabilizing drugs.

PMID- 20673794
TI  - Typhonium flagelliforme induces apoptosis in CEMss cells via activation of
      caspase-9, PARP cleavage and cytochrome c release: its activation coupled with
      G0/G1 phase cell cycle arrest.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The plant Typhonium flagelliforme (TF), commonly
      known as 'rodent tuber' in Malaysia, is often used as traditional remedy for
      cancer, including leukemia. AIM OF THE STUDY: We had previously identified
      morphologically that the linoleic acid rich fraction (DCM/F7) from the tubers of
      this plant induces selective anti-proliferative effects and apoptosis in CEMss
      cells. In this present study, we subjected the same DCM/F7 fraction to cell based
      activity analyses in order to determine the possible mechanism of cell death in
      leukemic CEMss cells in vitro. MATERIALS AND METHODS: Extraction of Typhonium
      flagelliforme tuber has done and fractionation has been done by vacuum liquid
      column chromatography. The anti-proliferative activity was assayed using MTT and
      the apoptosis detection was done by Annexin V and DNA laddering assay.
      Colorimetric caspase assay and immunoblot analysis were employed to detect the
      expression of protein associated with cell death. Cell cycle analysis was done
      using flow cytometry. RESULTS: We found that the cancer inhibitory effect of the
      DCM/F7 fraction in CEMss cells was 3 +/- 0.08 MUg/ml (IC(50)). An early apoptotic
      induction in CEMss cells was observed by Annexin V assay, which showed a clear
      dose-dependent DNA fragmentation being observed in gel electrophoresis at 10 and
      20 MUg/ml. The DCM/F7 fraction at 3 MUg/ml significantly arrested CEMss cells at
      G0/G1 phase (p<0.05). A constant but increasing pattern-related Sub-G0/G1 index
      was observed between 12 and 72 h treatment. In relation to this, we further
      investigated the biochemical events leading to cell death and found that the
      DCM/F7 fraction increased the cellular levels of caspase-3 and -9 on treated
      cells. Our results indicated that cytochrome c from mitochondria into the cytosol
      increased gradually as the DCM/F7 concentration increases, which later lead to
      the subsequent cleavage of PARP in to 85kDa fragments. On the contrary, Bcl-2
      protein was found to decrease concomitantly during treatment. CONCLUSIONS:
      Collectively, results presented in this study demonstrated that the DCM/F7
      fraction inhibited the proliferation of leukemia cells, leading to the programmed
      cell death, which was confirmed to be through the mitochondrial pathway.

PMID- 20673795
TI  - In vitro screening on beta-amyloid peptide production of plants used in
      traditional medicine for cognitive disorders.
AB  - AIM OF THE STUDY: The aim of the study was to investigate the activity on beta
      amyloid peptide production of crude extracts of 9 plant species traditionally
      used in Benin or in Madagascar for the treatment of cognitive disorders, in order
      to select candidates for Alzheimer's disease treatment. MATERIALS AND METHODS:
      For each species, hexane, dichloromethane, ethyl-acetate and water extracts were
      tested, at non-toxic concentrations, on CHO cells overexpressing the human
      neuronal beta-amyloid peptide precursor (APP695) to measure variations of APP
      processing (by Western-blotting) and, for the most active, of Abeta-amyloid
      production (by ECLIA). RESULTS: We observed, at non-toxic concentrations, a
      significant increase in CTF/APP ratio with Oldenlandia affinis cyclotide-enriched
      fraction, Prosopis africana EtOAc extract, Pterocarpus erinaceus aqueous extract
      and Trichilia emetica hexane extract. We also showed that the Pterocarpus
      erinaceus extract significantly decreased Abeta production, displaying effects
      similar to those of DAPT (gamma-secretase inhibitor) on APP processing, but may
      act on another inhibition site. CONCLUSION: These active extracts are worth
      further studies to isolate the compounds responsible for the observed activities,
      to analyze their mode of action and determine their clinical potentials.

PMID- 20673796
TI  - Progress on the transcriptomics of carcinogenic liver flukes of humans--unique
      biological and biotechnological prospects.
AB  - Liver flukes, such as Clonorchis sinensis and Opisthorchis viverrini, are food
      borne parasites that have a major impact on the health of humans and animals,
      particularly in Asia. However, the impact of C. sinensis and O. viverrini, in
      particular, is exacerbated in that these parasites can induce a malignant,
      untreatable cancer (cholangiocarcinoma, CCA) in chronically infected people. As a
      result, these flukes are classified as Group 1 carcinogens. Despite their
      substantial socio-economic importance, little is known about these parasites and
      their relationship with the definitive hosts at the molecular level. Here, we
      provide a background on these two carcinogenic flukes and review recent progress
      on characterizing their transcriptomes using next-generation technologies. We
      also describe the prospects that the transcriptomes of C. sinensis and O.
      viverrini provide as a resource for future -omic explorations and efforts to
      develop improved methods of intervention and control against these important
      pathogens and CCA, leading to biotechnological outcomes.

PMID- 20673797
TI  - CD133+ cells from human umbilical cord blood reduce cortical damage and promote
      axonal growth in neonatal rat organ co-cultures exposed to hypoxia.
AB  - To evaluate the effect of CD133(+) cells (endothelial progenitor cells) on the
      hypoxia-induced suppression of axonal growth of cortical neurons and the
      destruction of blood vessels (endothelial cells), we used anterograde axonal
      tracing and immunofluorescence in organ co-cultures of the cortex and the spinal
      cord from 3-day-old neonatal rats. CD133(+) cells prepared from human umbilical
      cord blood were added to the organ co-cultures after hypoxic insult, and axonal
      growth, vascular damage and apoptosis were evaluated. Anterograde axonal tracing
      with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate was used
      to analyze axonal projections from the cortex to the spinal cord. Immunolabeling
      co-cultured tissues of the cortex and the spinal cord were used to investigate
      the effect of CD133(+) cells on the survival of blood vessels and apoptosis in
      the brain cortex. Hypoxia remarkably suppressed axonal growth in organ co
      cultures of the cortex and the spinal cord, and this suppression was
      significantly restored by the addition of CD133(+) cells. CD133(+) cells also
      reduced the hypoxia-induced destruction of the cortical blood vessels and
      apoptosis. CD133(+) cells had protective effects on hypoxia-induced injury of
      neurons and blood vessels of the brain cortex in vitro. These results suggest
      that CD133(+) cell transplantation may be a possible therapeutic intervention for
      perinatal hypoxia-induced brain injury.

PMID- 20673798
TI  - A low molecular weight component of serum inhibits biofilm formation in
      Staphylococcus aureus.
AB  - Staphylococcus aureus has a variety of genes that can influence the process of
      biofilm formation. The ability to establish a biofilm is an important virulence
      factor for this pathogen, and yet, the regulation of this process in vivo is not
      well understood. S. aureus can form biofilms on intravenous catheters and this
      process plays a key role in the pathogenesis of catheter infections. In order to
      investigate whether or not serum is conducive to the process of biofilm
      formation, we grew S. aureus in serum and analyzed biofilm thickness and
      expression of biofilm-related genes. Whereas serum supported planktonic bacterial
      growth, it was a potent inhibitor of biofilm formation. The inhibitory serum
      component had a molecular weight less than 3000 kDa. The component was protease
      resistant and heat stable. The serum component induced a significant increase in
      the transcription of the intercellular adhesin gene icaA and the fibronectin
      binding protein gene fnbA. Transcription of other biofilm-related genes was
      affected in a strain-dependent manner. These results reveal that serum inhibits
      biofilm formation despite the fact that biofilms form on intravenous catheters.
      This may suggest that in vivo, biofilm formation is "selected for" by the force
      of blood flow and/or immune pressure rather than "induced" by serum.

PMID- 20673799
TI  - Nrf2 and DJ1 are consistently upregulated in inflammatory multiple sclerosis
      lesions.
AB  - Oxidative stress plays a major role in multiple sclerosis (MS), a chronic
      inflammatory central nervous system (CNS) disease. Invading leukocytes contribute
      to cell damage and demyelination by producing excessive amounts of cytotoxic
      mediators, including reactive oxygen species (ROS). To counteract the damaging
      effects of ROS the CNS is endowed with a repertoire of endogenous antioxidant
      enzymes, which are regulated by the transcription factor NF-E2-related factor 2
      (Nrf2). Upon exposure to ROS, Nrf2 translocates to the nucleus allowing
      transcriptional activation of various antioxidant enzymes. DJ1 is a protein that
      is involved in the stabilization of Nrf2 and hence acts as a positive regulator
      of Nrf2-driven antioxidant protection. Here, we investigate the (sub)cellular
      localization of Nrf2 and DJ1 in various MS lesion stages and show that Nrf2 is
      strikingly upregulated in active MS lesions, in both the nucleus and the
      cytoplasm of infiltrating macrophages and to a lesser extent in reactive
      astrocytes. Simultaneously, DJ1 protein expression is predominantly increased in
      astrocytes in both active and chronic inactive MS lesions compared to control
      brain tissue and normal-appearing white matter. Together, our findings suggest
      that persistent Nrf2-mediated transcription occurs in active MS lesions, but that
      this endogenous response is insufficient to prevent ROS-induced cellular damage,
      which is abundant in inflammatory MS lesions.

PMID- 20673800
TI  - Expression of immune-related genes in embryos and larvae of sea cucumber
      Apostichopus japonicus.
AB  - The echinoderm immunity system has been extensively investigated in adults in
      several classes such as echinoid and holothuroidea. However, the defense
      mechanism in embryos and larvae remains largely unexplored. To profile the immune
      related genes expression in embryos and larvae and to monitor the stimulation of
      the innate immune response by lipopolysaccharides (LPS) challenge, we
      investigated the expression patterns of nine immune-related genes in embryos and
      larvae of sea cucumber (Apostichopus japonicus) at eleven developmental stages
      using quantitative real-time PCR (qRT-PCR). The expression of six encoding
      proteins including heat shock protein70 (Hsp70), Hsp90, Hsp gp96, thymosin-beta,
      ferritin and DD104 protein was detected at all eleven development stages
      according to mRNA expression data. However, the expression of mannan-binding C
      type lectin (MBCL) was detected at early auricularia to juvenile stages, while
      lysozyme and serine proteinase inhibitor (SPI) were detected only at juvenile
      stage. Out of these nine genes, three (MBCL, lysozyme and SPI) were found to be
      up-regulated in mRNA expression upon LPS challenge, whereas the other six showed
      no significant change. Our study presents a first preliminary view into the
      expression patterns of immune-related genes at different developmental stages of
      sea cucumber, which increases the available information on echinoderm immunity.

PMID- 20673801
TI  - Weaving the (neuronal) web: fear learning in spider phobia.
AB  - Theories of specific phobias consider classical conditioning as a central
      mechanism in the pathogenesis and maintenance of the disorder. Although the
      neuronal network underlying human fear conditioning is understood in considerable
      detail, no study to date has examined the neuronal correlates of fear
      conditioning directly in patients with specific phobias. Using functional magnet
      resonance imaging (fMRI) we investigated conditioned responses using phobia
      relevant and non-phobia-relevant unconditioned stimuli in patients with specific
      phobias (n=15) and healthy controls (n=14) by means of a differential picture
      picture conditioning paradigm: three neutral geometric figures (conditioned
      stimuli) were followed by either pictures of spiders, highly aversive scenes or
      household items (unconditioned stimuli), respectively. Enhanced activations
      within the fear network (medial prefrontal cortex, anterior cingulate cortex,
      amygdala, insula and thalamus) were observed in response to the phobia-related
      conditioned stimulus. Further, spider phobic subjects displayed higher amygdala
      activation in response to the phobia-related conditioned stimulus than to the non
      phobia-related conditioned stimulus. Moreover, no differences between patients
      and healthy controls emerged regarding the non-phobia-related conditioned
      stimulus. The results imply that learned phobic fear is based on exaggerated
      responses in structures belonging to the fear network and emphasize the
      importance of the amygdala in the processing of phobic fear. Further, altered
      responding of the fear network in patients was only observed in response to the
      phobia-related conditioned stimulus but not to the non-phobia-related conditioned
      stimulus indicating no differences in general conditionability between patients
      with specific phobias and healthy controls.

PMID- 20673802
TI  - Neural substrates of implicit cueing effect on prospective memory.
AB  - Functional magnetic resonance imaging was used to examine the maintenance of
      intentions during an ongoing task involving implicit cues. Participants were
      required to detect target words while engaging in the ongoing task. Cues matched
      to the target category and cues matched to the action for targets were presented
      implicitly during the ongoing task. Implicit categorical target cues were found
      to enhance prospective memory performance, and implicit action cues accelerated
      responses more than irrelevant implicit cues in the prospective memory task. We
      found increased caudal anterior cingulate cortex (cACC) activity during the
      ongoing task with both implicit target and action cues, suggesting that alertness
      or preparatory attentional processes were strengthened by implicit cues. Implicit
      target cues elicited enhanced activity in the lateral anterior prefrontal cortex
      (Brodmann's area 10), which may be involved in dual processing of the ongoing
      task and the maintained intention. These results suggest that implicit cues may
      boost primitive attention toward an intended action and may be accessible to off
      line maintenance. The facilitation of prospective target detection and the action
      execution by target cues were associated with increased supplementary motor area
      (SMA) activity. In contrast, we found enhanced premotor cortex (PMC) activation
      with action cue during the prospective memory task, suggesting that the PMC may
      be involved in stimulus-induced and rather automatic action. These results
      demonstrate the effectiveness of implicit cues for examining the maintenance of
      intention. Overall, we found that implicit target cues can facilitate prospective
      memory performance, and implicit action cues can accelerate responses. The above
      mentioned neural underpinnings suggest that attentional and motor control
      processes are involved in the enhancement of prospective memory.

PMID- 20673803
TI  - Beyond revenge: neural and genetic bases of altruistic punishment.
AB  - It is still debated how altruistic punishment as one form of strong reciprocity
      has established during evolution and which motives may underlie such behavior.
      Recent neuroscientific evidence on the activation of brain reward regions during
      altruistic punishment in two-person one-shot exchange games suggests satisfaction
      through the punishment of norm violations as one underlying motive. In order to
      address this issue in more detail, we used fMRI during a one-shot economic
      exchange game that warrants strong reciprocity by introducing a third party
      punishment condition wherein revenge is unlikely to play a role. We report here
      that indeed, reward regions such as the nucleus accumbens showed punishment
      related activation. Moreover, we provide preliminary evidence that genetic
      variation of dopamine turnover impacts similarly on punishment-related nucleus
      accumbens activation during both first person and third party punishment. The
      overall pattern of results suggests a common cognitive-affective-motivational
      network as the driving force for altruistic punishment, with only quantitative
      differences between first person and third party perspectives.

PMID- 20673805
TI  - Plant microRNAs at a glance.

PMID- 20673804
TI  - Functioning of neural systems supporting emotion regulation in anxiety-prone
      individuals.
AB  - Previous neuroimaging studies suggest that prefrontal cortex (PFC) modulation of
      the amygdala and related limbic structures is an underlying neural substrate of
      effortful emotion regulation. Anxiety-prone individuals experience excessive
      negative emotions, signaling potential dysfunction of systems supporting down
      regulation of negative emotions. We examined the hypothesis that anxious
      individuals require increased recruitment of lateral and medial PFC to decrease
      negative emotions. An emotion regulation task that involved viewing moderately
      negative images was presented during functional magnetic resonance imaging
      (fMRI). Participants with elevated trait anxiety scores (n=13) and normal trait
      anxiety scores (n=13) were trained to reduce negative emotions using cognitive
      reappraisal. Blood oxygenation level-dependent (BOLD) changes were contrasted for
      periods when participants were reducing emotions versus when they were
      maintaining emotions. Compared to healthy controls, anxious participants showed
      greater activation of brain regions implicated in effortful (lateral PFC) and
      automatic (subgenual anterior cingulate cortex) control of emotions during down
      regulation of negative emotions. Left ventrolateral PFC activity was associated
      with greater self-reported reduction of distress in anxious participants, but not
      in healthy controls. These findings provide evidence of altered functioning of
      neural substrates of emotion regulation in anxiety-prone individuals. Anxious
      participants required greater engagement of lateral and medial PFC in order to
      successfully reduce negative emotions.

PMID- 20673806
TI  - The GATA-type transcriptional activator Gat1 regulates nitrogen uptake and
      metabolism in the human pathogen Cryptococcus neoformans.
AB  - Nitrogen uptake and metabolism are essential to microbial growth. Gat1 belongs to
      a conserved family of zinc finger containing transcriptional regulators known as
      GATA-factors. These factors activate the transcription of Nitrogen Catabolite
      Repression (NCR) sensitive genes when preferred nitrogen sources are absent or
      limiting. Cryptococcus neoformans GAT1 is an ortholog to the Aspergillus nidulans
      AreA and Candida albicans GAT1 genes. In an attempt to define the function of
      this transcriptional regulator in C. neoformans, we generated null mutants
      (gat1Delta) of this gene. The gat1 mutant exhibited impaired growth on all amino
      acids tested as sole nitrogen sources, with the exception of arginine and
      proline. Furthermore, the gat1 mutant did not display resistance to rapamycin, an
      immunosuppressant drug that transiently mimics a low-quality nitrogen source.
      Gat1 is not required for C. neoformans survival during macrophage infection or
      for virulence in a mouse model of cryptococcosis. Microarray analysis allowed the
      identification of target genes that are regulated by Gat1 in the presence of
      proline, a poor and non-repressing nitrogen source. Genes involved in ergosterol
      biosynthesis, iron uptake, cell wall organization and capsule biosynthesis, in
      addition to NCR-sensitive genes, are Gat1-regulated in C. neoformans.

PMID- 20673807
TI  - Modulation of the host immune response by cowpox virus.
AB  - Cowpox virus, a zoonotic poxvirus endemic to Eurasia, infects a large number of
      host species which makes its eradication impossible. The elimination of world
      wide smallpox vaccination programs renders the human population increasingly
      susceptible to infection by orthopoxviruses resulting in a growing number of
      zoonotic infections including CPXV transmitted from domestic animals to humans.
      The ability of CPXV to infect a wide range of mammalian host is likely due to the
      fact that, among the orthopoxviruses, CPXV encodes the most complete set of open
      reading frames expected to encode immunomodulatory proteins. This renders CPXV
      particularly interesting for studying poxviral strategies to evade and counteract
      the host immune responses.

PMID- 20673808
TI  - Platelets: pleiotropic roles in atherogenesis and atherothrombosis.
AB  - Platelets are small, anucleate blood elements of critical importance in
      cardiovascular disease. The ability of platelets to activate and aggregate to
      form blood clots in response to endothelial injury, such as plaque rupture, is
      well established. These cells are therefore important contributors to ischaemia
      in atherothrombosis, and antiplatelet therapy is effective for this reason.
      However, growing evidence suggests that platelets are also important mediators of
      inflammation and play a central role in atherogenesis itself. Interactions
      between activated platelets, leukocytes and endothelial cells trigger autocrine
      and paracrine activation signals, resulting in leukocyte recruitment at and into
      the vascular wall. Direct physical interaction may contribute also, through
      platelet adhesion molecules assisting localization of monocytes to the site of
      atherogenesis and platelet granule release contributing to the chronic
      inflammatory milieu which leads to foam cell development and accelerated
      atherogenesis. Recent studies have shown that antiplatelet therapy in animal
      models of accelerated atherogenesis can lead to decreased plaque size and improve
      plaque stability. This review examines the complexity of platelet function and
      the nature of interactions between activated platelets, leukocytes and
      endothelial cells. We focus on the growing body of evidence that platelets play a
      critical role in atherogenesis and contribute to progression of atherosclerosis.

PMID- 20673809
TI  - Oxidation in the nucleotide pool, the DNA damage response and cellular
      senescence: Defective bricks build a defective house.
AB  - Activation of persistent DNA damage response (DDR) signaling is associated with
      the induction of a permanent proliferative arrest known as cellular senescence, a
      phenomenon intrinsically linked to both tissue aging as well as tumor
      suppression. The DNA damage observed in senescent cells has been attributed to
      elevated levels of reactive oxygen species (ROS), failing DNA damage repair
      processes, and/or oncogenic activation. It is not clear how labile molecules such
      as ROS are able to damage chromatin-bound DNA to a sufficient extent to invoke
      persistent DNA damage and DDR signaling. Recent evidence suggests that the
      nucleotide pool is a significant target for oxidants and that oxidized
      nucleotides, once incorporated into genomic DNA, can lead to the induction of a
      DNA strand break-associated DDR that triggers senescence in normal cells and in
      cells sustaining oncogene activation. Evasion of this DDR and resulting
      senescence is a key step in tumor progression. This review will explore the role
      of oxidation in the nucleotide pool as a major effector of oxidative stress
      induced genotoxic damage and DDR in the context of cellular senescence and
      tumorigenic transformation.

PMID- 20673810
TI  - Protective effects of garlic extract and vitamin C against in vivo cypermethrin
      induced cytogenetic damage in rat bone-marrow.
AB  - The cytogenetic damage inflicted by the synthetic pyrethroid insecticide
      cypermethrin (CYP) on the bone-marrow of male white rats, as well as possible
      protective role of two natural elements: garlic extract (GRE, 500mg/kg) and
      vitamin C (VTC, 20mg/kg) against the mutagenic potential of the insecticide were
      assessed. CYP was orally intubated in a single treatment (1/2 LD(50)) or in
      repeated treatments (1/5 LD(50) daily, for 5 successive days), either alone, or
      concomitantly with repeated oral intubations (5 successive days) of each
      individual putative protector, or with their combination (GRE or/and VTC). One
      hundred and twenty male rats were divided over into five groups of each 24
      animals. The groups received nothing, a single dose or repeated treatments with
      insecticide alone, or associated with putative natural elements, separately or in
      combinations. Animals were sacrificed at their scheduled times and their femoral
      bone-marrows were flushed out to be utilized in the micronucleus test and
      metaphase chromosomal aberration assay. The results show that CYP administration
      significantly induced clastogenic effects, as revealed by the significant
      increase in the mean frequencies of micronucleated polychromatic erythrocytes and
      various structural chromosomal aberrations in bone-marrow metaphase cells of all
      groups of treated rats. On the other hand, this investigation clearly revealed
      the protective role of GRE and VTC, either each alone or in combination, against
      the mutagenic potential of cypermethrin: the garlic extract was often more
      efficient in its protective action against the insecticide toxicity than vitamin
      C. while the combination of both natural elements produced, in most cases, a more
      pronounced protective effect than when each was administered alone.

PMID- 20673811
TI  - Survey of gastrointestinal parasitic infections of beef cattle in regions under
      Mediterranean weather in Greece.
AB  - Gastrointestinal (GI) parasitic infections of beef cattle were investigated in 15
      farms from 3 different regions of Greece, characterized by temperate
      Mediterranean climate, during two years. A total of 262 faecal samples were
      collected. Helminth eggs were detected in 42 (16%) samples. Strongyle-type eggs
      were found in 28 (10.7%) samples, Strongyloides spp. and Toxocara spp. eggs in 8
      (3.1%) samples each, and Capillaria spp. and Moniezia spp. eggs in 1 (0.4%)
      sample each. Coccidian oocysts were found in 123 (46.9%) samples. A logistic
      regression model showed that the age of animals, the number of employees, and the
      region of animals were associated with coccidian infections. There was almost a
      four-fold increase in the risk of coccidian infections in calves less than 12
      months old compared with animals that were more than 36 months old (p<0.05). The
      risk of coccidian infections was 0.07, 0.18 and 0.27-fold lower for farms with 1,
      2 and 3 employees respectively compared to farms with 4 employees; farms with
      less than 4 employees had a protective effect (p<0.05 in all cases). Almost a
      four-fold increased risk of coccidian infections was shown for animals from
      Epirus compared with those from Thessaly (p<0.05). These findings are useful to
      formulate appropriate control strategies for coccidian parasites of beef cattle
      in Greece and other areas with similar climatic conditions.

PMID- 20673812
TI  - The prevalence and diagnostic/prognostic utility of sinus arrhythmia in the
      evaluation of congenital long QT syndrome.
AB  - BACKGROUND: Congenital long QT syndrome (LQTS) affects 1 in 2,500 people and can
      cause syncope and sudden death. Sinus arrhythmia (SA) is nonpathologic baseline
      respiratory variation of the RR interval. OBJECTIVE: This study sought to
      determine the frequency of SA and its clinical significance among patients with
      LQTS. METHODS: We performed an institutional review board-approved retrospective
      review of all patients (N = 571) evaluated in our LQTS clinic from 7/2000 to
      3/2008 diagnosed with LQTS (N = 281) or dismissed as otherwise normal (N = 290).
      Blinded to diagnosis, the first available electrocardiogram for each patient was
      examined to quantitate RR interval variability. RESULTS: Overall, 151 of 281
      patients (54%) with LQTS (159 female patients, average age 21.8 +/- 16.5 years,
      average QTc 466 +/- 43 ms) had SA with an average RR variability of 13% +/- 8%
      compared with 201 of 290 (69%) patients dismissed as normal (178 female patients,
      average age 21.7 +/- 16 years, average QTc 424 +/- 30 ms) who demonstrated SA
      with RR variability of 16% +/- 10% (P < .0001). These differences remained
      significant when patients on concurrent beta-blocker therapy were excluded (P <
      .001). SA was least common in LQT3 (23%) compared with LQT1 (61%, P < .005) and
      LQT2 (51%, P = .055). Patients presenting with torsades de pointes or aborted
      cardiac arrest had lower RR variability (10% +/- 7%, P < .03). CONCLUSION: SA
      frequency and magnitude of RR variability was lower among patients with LQTS
      compared with those patients dismissed as otherwise normal. This attenuation in
      RR interval variability remained when patients on beta-blocker therapy were
      excluded. Although the presence/absence of sinus arrhythmia is of little
      diagnostic value due to cohort overlap, LQTS patients with negligible RR interval
      variation may be at higher risk.

PMID- 20673813
TI  - Role of CaMKII in cardiovascular health, disease, and arrhythmia.

PMID- 20673814
TI  - Power and pitfalls of using transgenic mice to optimize therapy for CPVT: a need
      for prospective placebo-controlled clinical trials in genetic arrhythmia
      disorders.

PMID- 20673815
TI  - Population aging and its impacts: strategies of the health-care system in Taipei.
AB  - Taiwan is one of the fastest aging countries in the world. As such, the
      government has developed various strategies to promote an age-friendly health
      care system. Health services are supported by National Health Insurance (NHI),
      which insures over 97% of citizens and over 99% of health-care institutes. The
      current health-care system has difficulties in caring for older patients with
      multiple comorbidities, complex care needs, functional impairments, and post
      acute care needs. Taipei, an international metropolis with a well-preserved
      tradition of filial piety in Chinese societies, has developed various strategies
      to overcome the aforementioned barriers to an age-friendly health-care system.
      These include an emphasis on general medical care and a holistic approach in all
      specialties, development of a geriatrics specialty training program, development
      of post-acute services, and strengthening of linkages between health and social
      care services. Despite achievements thus far, challenges still include creating a
      more extensive integration between medical specialties, promotion of an
      interdisciplinary care model across specialties and health-care settings, and
      integration of health and social care services. The experiences of Taipei in
      developing an age-friendly health-care service system may be a culturally
      appropriate model for other Chinese and Asian communities.

PMID- 20673816
TI  - Role of intra operative cholangiogram in current day practice.
AB  - The role of Intra Operative Cholangiogram during laparoscopic cholecystectomy
      remains controversial. This review discusses the modalities used in the pre- and
      peri-operative assessment of Common Bile Duct. It also discusses the advantages
      and disadvantages of selective and routine IOC. In this review we explore the
      role of Intra Operative Cholangiogram in current day practice.

PMID- 20673817
TI  - Fungal infections of the nervous system: current perspective and controversies in
      management.
AB  - In the last two decades, more elaborative use of intensive care units for serious
      medical disorders, advancements in transplant procedures and concomitant use of
      immunosuppressive therapies as well as the pandemic spread of HIV, etc. have
      increased the incidence of systemic fungal infections, especially life
      threatening central nervous system (CNS) infections. The CNS fungal infections
      present with various clinical syndromes: meningitis; encephalitis;
      hydrocephalus/raised intracranial pressure (raised ICP); space occupying lesions;
      orbito-rhino-cerebral syndromes; acute cerebro-vascular events and spinal
      infections. However, the common presentations among these ones are basal
      meningitis, hydrocephalus, space occupying lesions (cerebral abscesses and
      granulomas) and stroke syndromes. Clinical picture may mimic tubercular
      meningitis and therefore, needs careful evaluation. The CNS mycoses carry higher
      risks of morbidities and mortality as compared to other infective processes and
      therefore promptly require precise diagnosis and appropriate medical and/or
      surgical management strategies to optimize the outcome. Among the antifungal
      drugs, the Amphotericin B had remained first line of therapy for many decades in
      invasive fungal infections but is not effective in many forms of mycoses.
      Fortunately, many useful antifungal drugs were introduced during the last two
      decades. Initially, the lipid based formulations of the Amphotericin B, then the
      new triazoles and most recently, echinocandins. These medications are used more
      frequently in combinations. Now evidence based data are gathering together in
      favor of their usefulness in the management of invasive fungal infections. But
      still, many questions are unanswered and controversies persist relating to their
      selection and use.

PMID- 20673818
TI  - Possible detrimental effects of neurosurgical irrigation fluids on neural tissue:
      an evidence based analysis of various irrigants used in contemporary
      neurosurgical practice.
AB  - Physiological saline and other solutions used as irrigation fluids during
      neurosurgical procedures have long been debated to cause adverse effects on
      neural tissue. Laboratory based research over the past fifty years has described
      the possible harm caused to central nervous system cells by normal saline, and
      has advocated the use of safer alternatives such as lactated Ringer's solution
      and artificial cerebrospinal fluid. However, there is a dearth of corresponding
      clinical studies to support this standpoint. Worldwide, normal saline remains the
      most widely used neurosurgical irrigation fluid. We have attempted to document
      the preference of practicing neurosurgeons worldwide regarding the irrigation
      fluids via an electronic mail survey, and have analyzed the available evidence on
      the relative safety of various irrigation fluids. We recommend the use of
      lactated Ringer's solution and artificial cerebrospinal fluid as neurosurgical
      irrigants, especially during neuroendoscopy and longer procedures requiring
      application of copious amount of irrigation fluid.

PMID- 20673819
TI  - Two cases of Noonan syndrome with severe respiratory and gastroenteral
      involvement and the SOS1 mutation F623I.
AB  - Noonan syndrome (NS) is an autosomal dominant, inherited disorder characterized
      by facial dysmorphism, congenital heart defects, and reduced postnatal growth.
      Dysregulated RAS-MAPK signalling is the common molecular basis for NS, a
      genetically heterogeneous disease. Germline mutations in genes encoding small
      GTPases of the RAS family (KRAS and NRAS), modulators of RAS function (PTPN11,
      SOS1 and SHOC2) or downstream signal transducers (RAF1) are causative for NS.
      SOS1 is the second major gene for NS after PTPN11. Compared to patients with
      mutations in other genes, SOS1 mutation-positive individuals in general tend to
      have a more favorable outcome, with less short stature and cognitive impairment.
      We describe two unrelated patients with NS carrying the same heterozygous SOS1
      missense mutation (c.1867T > A/p.F623I). The phenotype of both patients is
      remarkable as they show uncommon clinical features such as pulmonary
      lymphangiectasis, congenital pleural effusions, severe feeding problems, and
      laryngomalacia. These findings may be related to the specific mutation present in
      our two patients, or be part of the SOS1 phenotype. Detailed clinical assessment
      of large cohorts of patients with NS and SOS1 mutation is required to clarify
      this initial observation.

PMID- 20673820
TI  - Delayed bone age due to a dual effect of FGFR3 mutation in Achondroplasia.
AB  - Achondroplasia (ACH), the most common form of human dwarfism is caused by a
      mutation in the Fibroblast Growth Factor Receptor 3 (FGFR3) gene, resulting in
      constitutive activation of the receptor. Typical radiological features include
      shortening of the tubular bones and macrocephaly, due to disruption of
      endochondral ossification. Consequently, FGFR3 has been described as a negative
      regulator of bone growth. Studying a large cohort of ACH patients, a delay in
      bone age was observed shortly after birth (for boys p=2.6*10(-9) and for girls
      p=1.2*10(-8)). This delay was no longer apparent during adolescence. In order to
      gain further insight into bone formation, bone development was studied in a
      murine model of chondrodysplasia (Fgfr3(Y367C/+)) from birth to 6weeks of age.
      Delayed bone age was also observed in Fgfr3(Y367C/+) mice at 1week of age
      followed by an accelerated secondary ossification center formation. A low level
      of chondrocyte proliferation was observed in the normal growth plate at birth,
      which increased with bone growth. In the pathological condition, a significantly
      high level of proliferative cells was present at birth, but exhibited a transient
      decrease only to rise again subsequently. Histological and in situ analyses
      suggested the altered endochondral ossification process may result from delayed
      chondrocyte differentiation, disruption of vascularization and osteoblast
      invasion of the femur. All these data provide evidence that FGFR3 regulates
      normal chondrocyte proliferation and differentiation during bone growth and
      suggest that constitutive activation of the receptor disrupts both processes.
      Therefore, the consequences of FGFR3 activation on the physiological process of
      bone development appear to be dependent on spatial and temporal occurrence. In
      conclusion, these observations support the notion that FGFR3 has a dual effect,
      as both a negative and a positive regulator of the endochondral ossification
      process during post-natal bone development.

PMID- 20673821
TI  - Do drastic weather effects on diet influence changes in chemical composition,
      mechanical properties and structure in deer antlers?
AB  - We attempted to determine why after an exceptionally hard winter deer antlers
      fractured more often than usual. We assessed mechanical properties, structural
      variables and mineral composition of deer antlers grown in a game estate (LM)
      after freezing temperatures (late winter frosts, LWF), which resulted in high
      incidence of antler fractures despite being grown later in the year, and those
      grown after a standard winter (SW). Within each year, specimens from broken and
      intact antlers were assessed. LWF was associated with reduced impact energy (U)
      and somewhat reduced work to peak force (W), Young's modulus (E) and physical
      density, as well as cortical thickness. LWF was associated with considerably
      increased Si and reduced Na. In each year, broken antlers had lower Mn, P and
      physical density, and they had more Na and B than unbroken antlers. Because no
      such effect was found in farmed deer fed whole meal, and because freezing in
      plants usually produces an increase in Si content, which in turn reduces Mn, it
      is likely that LWF produced a diet rich in Si and low in Mn. Because antlers are
      grown transferring calcium phosphate from the own skeleton and Ca/P levels were
      slightly reduced, it seems likely that Mn reduction may have increased antler
      fractures. A comparison between farm deer and those in another game estate (LI)
      also shows a link between lower Mn content and lower W. Thus, small changes in
      minor bone minerals, probably induced by diet, may have marked effects in
      mechanical properties of bone.

PMID- 20673822
TI  - Isolation of murine bone marrow derived mesenchymal stem cells using Twist2 Cre
      transgenic mice.
AB  - While human bone marrow derived mesenchymal stem cells (BMSCs) are of great
      interest for their potential therapeutic value, their murine equivalent remains
      an important basic research model that can provide critical insights into the
      biology of this progenitor cell population. Here we present a novel transgenic
      strategy that allowed for the selective identification and isolation of murine
      BMSCs at the early stages of stromal cell culture. This strategy involved
      crossing Twist2 -Cre mice with Cre reporter mice such as Z/EG or Ai9, which
      express EGFP or Tomato fluorescent protein, respectively, upon Cre mediated
      excision of a stop sequence. Using this approach, we identified an adherent
      fluorescent protein+cell population (T2C+) that is present during the earliest
      stages of colony formation and by day 5 of culture represents ~20% of the total
      cell population. Cell surface profiling by flow cytometry showed that T2C+cells
      are highly positive for SCA1 and CD29 and negative for CD45, CD117, TIE2, and
      TER119. Isolation of T2C+cells by FACS selected for a cell population with
      skeletal potential that can be directed to differentiate into osteoblasts,
      adipocytes, or chondrocytes. We also demonstrated in a calvarial bone defect
      model that T2C+cells retain a strong efficacy for osteogenic repair and can
      support a hematopoietic environment. Collectively, these studies provide evidence
      that the Twist2-Cre x Cre reporter breeding strategy can be used to positively
      identify and isolate multipotent murine BMSCs.

PMID- 20673823
TI  - Identification of an Edwardsiella tarda surface antigen and analysis of its
      immunoprotective potential as a purified recombinant subunit vaccine and a
      surface-anchored subunit vaccine expressed by a fish commensal strain.
AB  - Edwardsiella tarda is the etiological agent of edwardsiellosis, a systematic
      disease that affects a wide range of marine and freshwater fish cultured
      worldwide. In order to identify E. tarda antigens with vaccine potential, we in
      this study conducted a systematic search for E. tarda proteins with secretion
      capacity. One of the proteins thus identified was Esa1, which contains 795 amino
      acid residues and shares extensive overall sequence identities with the D15-like
      surface antigens of several bacterial species. In silico analyses indicated that
      Esa1 localizes to outer membrane and possesses domain structures that are
      conserved among bacterial surface antigens. The vaccine potential of purified
      recombinant Esa1 was examined in a Japanese flounder (Paralichthys olivaceus)
      model, which showed that fish vaccinated with Esa1 exhibited a high level of
      survival and produced specific serum antibodies. Passive immunization of naive
      fish with antisera raised against Esa1 resulted in significant protection against
      E. tarda challenge. Taking advantage of the secretion capacity of Esa1 and the
      natural gut-colonization ability of a fish commensal strain, we constructed an
      Esa1-expressing recombinant strain, FP3/pJsa1. Western immunoblot and
      agglutination analyses showed that FP3/pJsa1 produces outer membrane-localized
      Esa1 and forms aggregates in the presence of anti-Esa1 antibodies. Vaccination
      analyses showed that FP3/pJsa1 as an intraperitoneal injection vaccine and an
      oral vaccine embedded in alginate microspheres produced relative percent survival
      rates of 79% and 52%, respectively, under severe challenging conditions that
      resulted in 92-96% mortality in control fish. Further analyses showed that
      following oral vaccination, FP3/pJsa1 was able to colonize in the gut but unable
      to disseminate into other tissues. Together these results indicate that Esa1 is a
      protective immunogen and an effective oral vaccine when delivered by FP3/pJsa1 as
      a surface-anchored antigen.

PMID- 20673824
TI  - Safety analysis of a Vero-cell culture derived Japanese encephalitis vaccine,
      IXIARO (IC51), in 6 months of follow-up.
AB  - Japanese encephalitis (JE) is the most common viral encephalitis in Asia. IXIARO
      is a Vero cell-derived, inactivated JE virus vaccine which has recently been
      approved in the US, Europe, Canada and Australia (trade name JESPECT). This
      overview of the safety and tolerability of IXIARO, for 6 months after the first
      vaccination in 7 Phase III trials, includes: 3558 subjects with at least one
      IXIARO vaccination, 435 subjects with a JE-VAX (manufactured by BIKEN,
      distributed by Sanofi Pasteur) vaccination, and 657 with phosphate-buffered
      saline solution with 0.1% Al(OH)(3) (PBS+Alum) control vaccination. The
      percentage of subjects reporting solicited local adverse events (AEs) with IXIARO
      (54%) was similar to PBS+Alum vaccination (56%) as were solicited systemic
      adverse events (40% IXIARO; 40% PBS+Alum vaccination). JE-VAX showed a higher
      frequency of subjects with solicited local adverse events (61%) but a slightly
      lower frequency of subjects with solicited systemic adverse events (36%). The
      frequency of subjects with any solicited and unsolicited AE with IXIARO (64%) was
      also similar to PBS+Alum vaccination (61%) and JE-VAX (64%); as for subjects with
      serious AEs (1% IXIARO; 2% PBS+Alum vaccination, 1% JE-VAX). No serious allergic
      reactions were observed in any group. This safety analysis indicates that IXIARO
      has a favorable safety profile, comparable to PBS+Alum control vaccination and
      appears to have a better local tolerability profile than JE-VAX.

PMID- 20673825
TI  - Implementing a birth dose of hepatitis B vaccine for home deliveries in Africa-
      too soon?
AB  - Despite the recommendation of the World Health Organization (WHO) to provide the
      first hepatitis B vaccine dose at birth (within 24h), there are epidemiological,
      economic and logistical reasons why this may not be the best approach for home
      births in Africa. The WHO policy presupposes that the epidemiology of hepatitis B
      infection in Africa is similar to the rest of the world and that the
      organizational, infrastructural and financial support is adequate. While babies
      born in health facilities may be relatively easy to immunize at birth, health
      systems and infrastructures in many resource-poor countries in Africa would be
      severely challenged, if required to reach home deliveries within 24h of birth.

PMID- 20673826
TI  - Time course of neuronal damage in the hippocampus following lithium-pilocarpine
      status epilepticus in 12-day-old rats.
AB  - Status epilepticus (SE) leads to serious damage in hippocampus of the adult
      brain. Much less is known about immature brain where neuronal degeneration may
      have different localization and time course. Lithium-pilocarpine SE was induced
      in 12-day-old male Wistar rats. Six different intervals after SE (from 4 h to 1
      week) were studied using Fluoro-Jade B staining. Three to four animals were used
      for every interval. Severity of damage in individual parts of hippocampal
      formation was semi-quantified. A consistent neuronal damage occurred in all
      hippocampal fields (CA 1, CA 3, dentate gyrus) at all survival intervals.
      Hippocampal fields CA 1 and CA 3 exhibited degeneration of interneurons located
      mainly in stratum oriens and pyramidale at shorter intervals (4-12h). Massive
      degeneration of pyramidal cells started at 24h in CA 1 and at 48 h in CA 3.
      Dentate gyrus exhibited degenerating neurons in granular layer with a peak at
      short intervals (4-8 h), and molecular layer was spared. The lower blade of
      dentate gyrus was more affected than the upper blade. Damage of hilar neurons was
      negligible. Our results demonstrate that SE elicited in immature rats causes
      acute neurodegeneration in the hippocampus. Time course of this degeneration is
      different for individual parts of hippocampal formation and for individual cell
      types.

PMID- 20673827
TI  - Review on anti-lipoprotein lipase antibodies.
AB  - Lipoprotein lipase (LPL) is a member of the lipase family, and LPL is known to
      hydrolyze triglyceride molecules found in lipoprotein particles. Understanding
      the pathogenesis of atherosclerosis in autoimmune diseases, particularly systemic
      lupus erythematosus (SLE), is vital to reduce morbidity and mortality of this
      disease. It is now recognized that SLE has a particular pattern of
      dyslipoproteinemia characterized by low HDL levels and increased triglycerides,
      which is aggravated by flare. Antilipoprotein lipase (anti-LPL) antibodies have
      been recently described in rheumatic diseases, mainly in SLE and systemic
      sclerosis (SSc). Several studies have reported a close link between antibodies,
      inflammation and lipoprotein levels and an increased risk of cardiovascular
      damage in this particular group of patients. These studies have emphasized the
      importance of rigorous clinical control of disease activity and prevention of
      cardiovascular risk factors. This review summarized the studies that have
      discussed the presence of anti-LPL in rheumatic diseases and other conditions and
      analyzed the importance of this antibody in the complex atherosclerotic process
      in autoimmune diseases.

PMID- 20673828
TI  - Role of en and novel interactions between msh, ind, and vnd in dorsoventral
      patterning of the Drosophila brain and ventral nerve cord.
AB  - Subdivision of the neuroectoderm into discrete gene expression domains is
      essential for the correct specification of neural stem cells (neuroblasts) during
      central nervous system development. Here, we extend our knowledge on dorsoventral
      (DV) patterning of the Drosophila brain and uncover novel genetic interactions
      that control expression of the evolutionary conserved homeobox genes ventral
      nervous system defective (vnd), intermediate neuroblasts defective (ind), and
      muscle segment homeobox (msh). We show that cross-repression between Ind and Msh
      stabilizes the border between intermediate and dorsal tritocerebrum and
      deutocerebrum, and that both transcription factors are competent to inhibit vnd
      expression. Conversely, Vnd segment-specifically affects ind expression; it
      represses ind in the tritocerebrum but positively regulates ind in the
      deutocerebrum by suppressing Msh. These data provide further evidence that in the
      brain, in contrast to the trunc, the precise boundaries between DV gene
      expression domains are largely established through mutual inhibition. Moreover,
      we find that the segment-polarity gene engrailed (en) regulates the expression of
      vnd, ind, and msh in a segment-specific manner. En represses msh and ind but
      maintains vnd expression in the deutocerebrum, is required for down-regulation of
      Msh in the tritocerebrum to allow activation of ind, and is necessary for
      maintenance of Ind in truncal segments. These results indicate that input from
      the anteroposterior patterning system is needed for the spatially restricted
      expression of DV genes in the brain and ventral nerve cord.

PMID- 20673829
TI  - Diversification of muscle types: recent insights from Drosophila.
AB  - Myogenesis is a highly conserved process ending up by the formation of
      contracting muscles. In Drosophila embryos, myogenesis gives rise to a
      segmentally repeated array of thirty distinct fibres, each of which represents an
      individual muscle. Since Drosophila offers a large range of genetic tools for
      easily testing gene functions, it has become one of the most studied and
      consequently best-described model organisms for muscle development. Over the last
      two decades, the Drosophila model system has enabled major advances in our
      understanding of how the initially equivalent mesodermal cells become competent
      for entering myogenic differentiation and how each distinct type of muscle is
      specified. Here we present an overview of Drosophila muscle development with a
      special focus on the diversification of muscle types and the genes that control
      acquisition of distinct muscle properties.

PMID- 20673830
TI  - Calpain inhibition attenuates intracellular changes in muscle cells in response
      to extracellular inflammatory stimulation.
AB  - Idiopathic inflammatory myopathies (IIMs), comprising of polymyositis,
      dermatomyositis, and inclusion-body myositis, are characterized by muscle
      weakness and various types of inflammatory changes in muscle cells. They also
      show non-inflammatory changes, including perifascicular atrophy, mitochondrial
      changes, and amyloid protein accumulation. It is possible that some
      molecules/mechanisms bridge the extracellular inflammatory stimulation and
      intracellular non-inflammatory changes. One such mechanism, Ca(2+) influx leading
      to calpain activation has been proposed. In this study, we demonstrated that post
      treatment with calpeptin (calpain inhibitor) attenuated intracellular changes to
      prevent apoptosis (Wright staining) through both mitochondrial pathway (increase
      in Bax:Bcl-2 ratio) and endoplasmic reticulum stress pathway (activation of
      caspase-12), which were induced by interferon-gamma (IFN-gamma) stimulation in
      rat L6 myoblast cells. Our results also showed that calpeptin treatment inhibited
      the expression of calpain, aspartyl protease cathepsin D, and amyloid precursor
      protein. Thus, our results indicate that calpain inhibition plays a pivotal role
      in attenuating muscle cell damage from inflammatory stimulation due to IFN-gamma,
      and this may suggest calpain as a possible therapeutic target in IIMs.

PMID- 20673831
TI  - Metabolic responses of Glossina pallidipes (Diptera: Glossinidae) puparia exposed
      to oxygen and temperature variation: implications for population dynamics and
      subterranean life.
AB  - Understanding the factors affecting insect gas exchange in subterranean
      environments is critical to understanding energy budgets and predicting mortality
      under field conditions. Here, we examine the metabolic rate (MR) responses of
      tsetse puparia, which remain underground for ca. 1 month in this life-stage, to
      varying oxygen and temperature. First, the effects of temperature and oxygen on
      puparial MR were investigated by ramping temperature from 15 to 35 degrees C
      under 10, 21 or 40% O(2). Overall, temperature was the dominant effect on
      puparial MR although O(2) had small but significant impacts. Second, critical
      O(2) concentration (P(CRIT)) for MR of puparia was examined across a range of
      oxygen concentrations (0-40%). P(CRIT) was 6% O(2) which is similar to P(CRIT) in
      other basal arthropods but relatively high for inactive or subterranean insects.
      Third, we asked if puparia exposed to anoxia might experience oxygen debt,
      potentially indicative of anaerobic metabolism or cellular repair. Metabolic
      responses to anoxia were limited or insignificant, but MR was marginally elevated
      (~ 15%) in anoxia-exposed (4h) puparia by 12h post-anoxia. Finally, we examined
      the ability of puparia to withstand water submersion, thus simulating flooding
      conditions frequently experienced in tropical soil habitats. Puparia were unable
      to survive submersion for >24h suggesting limited flooding tolerance. These novel
      results suggest that soil conditions experienced by puparia should not be
      limiting for MR, except possibly under high temperature-low O(2) conditions. Due
      to a large safety margin between P(CRIT) and soil oxygen levels and limited
      effects of oxygen on metabolism during temperature ramping experiments, we
      suggest that Glossina pallidipes puparia are not particularly susceptible to
      oxygen availability in their natural environment. However, soil flooding
      associated with tropical rainfall likely imposes strong selection on tsetse
      populations and may have had important effects for tsetse energy budgets and
      evolution.

PMID- 20673832
TI  - Redox regulation of Plasmodium falciparum ornithine delta-aminotransferase.
AB  - Ornithine delta-aminotransferase (OAT) of the malaria parasite Plasmodium
      falciparum catalyzes the reversible conversion of ornithine into glutamate-5
      semialdehyde and glutamate and is-in contrast to its human counterpart-activated
      by thioredoxin (Trx) by a factor of 10. Trx, glutaredoxin, and plasmoredoxin are
      redox-active proteins that play a crucial role in the maintenance and control of
      redox reactions, and were shown to interact with P. falciparum OAT. OAT, which is
      involved in ornithine homeostasis and proline biosynthesis, is essential for
      mitotic cell division in rapidly growing cells, thus representing a potential
      target for chemotherapeutic intervention. Here we report the three-dimensional
      crystal structure of P. falciparum OAT at 2.3 A resolution. The overall structure
      is very similar to that of the human OAT. However, in plasmodial OAT, the loop
      involved in substrate binding contains two cysteine residues, which are lacking
      in human OAT. Site-directed mutagenesis of these cysteines and functional
      analysis demonstrated that Cys154 and Cys163 mediate the interaction with Trx.
      Interestingly, the Cys154->Ser mutant has a strongly reduced specific activity,
      most likely due to impaired binding of ornithine. Cys154 and Cys163 are highly
      conserved in Plasmodium but do not exist in other organisms, suggesting that
      redox regulation of OAT by Trx is specific for malaria parasites. Plasmodium
      might require a tight Trx-mediated control of OAT activity for coordinating
      ornithine homeostasis, polyamine synthesis, proline synthesis, and mitotic cell
      division.

PMID- 20673834
TI  - The crystal structure of the [NiFe] hydrogenase from the photosynthetic bacterium
      Allochromatium vinosum: characterization of the oxidized enzyme (Ni-A state).
AB  - The crystal structure of the membrane-associated [NiFe] hydrogenase from
      Allochromatium vinosum has been determined to 2.1 A resolution. Electron
      paramagnetic resonance (EPR) and Fourier transform infrared spectroscopy on
      dissolved crystals showed that it is present in the Ni-A state (>90%). The
      structure of the A. vinosum [NiFe] hydrogenase shows significant similarities
      with [NiFe] hydrogenase structures derived from Desulfovibrio species. The amino
      acid sequence identity is ~ 50%. The bimetallic [NiFe] active site is located in
      the large subunit of the heterodimer and possesses three diatomic non-protein
      ligands coordinated to the Fe (two CN(-) , one CO). Ni is bound to the protein
      backbone via four cysteine thiolates; two of them also bridge the two metals. One
      of the bridging cysteines (Cys64) exhibits a modified thiolate in part of the
      sample. A mono-oxo bridging ligand was assigned between the metal ions of the
      catalytic center. This is in contrast to a proposal for Desulfovibrio sp.
      hydrogenases that show a di-oxo species in this position for the Ni-A state. The
      additional metal site located in the large subunit appears to be a Mg(2+) ion.
      Three iron-sulfur clusters were found in the small subunit that forms the
      electron transfer chain connecting the catalytic site with the molecular surface.
      The calculated anomalous Fourier map indicates a distorted proximal iron-sulfur
      cluster in part of the crystals. This altered proximal cluster is supposed to be
      paramagnetic and is exchange coupled to the Ni(3+) ion and the medial
      [Fe(3)S(4)](+) cluster that are both EPR active (S=1/2 species). This finding of
      a modified proximal cluster in the [NiFe] hydrogenase might explain the
      observation of split EPR signals that are occasionally detected in the oxidized
      state of membrane-bound [NiFe] hydrogenases as from A. vinosum.

PMID- 20673833
TI  - Structure of the RNA binding domain of a DEAD-box helicase bound to its ribosomal
      RNA target reveals a novel mode of recognition by an RNA recognition motif.
AB  - DEAD-box RNA helicases of the bacterial DbpA subfamily are localized to their
      biological substrate when a carboxy-terminal RNA recognition motif domain binds
      tightly and specifically to a segment of 23S ribosomal RNA (rRNA) that includes
      hairpin 92 of the peptidyl transferase center. A complex between a fragment of
      23S rRNA and the RNA binding domain (RBD) of the Bacillus subtilis DbpA protein
      YxiN was crystallized and its structure was determined to 2.9 A resolution,
      revealing an RNA recognition mode that differs from those observed with other RNA
      recognition motifs. The RBD is bound between two RNA strands at a three-way
      junction. Multiple phosphates of the RNA backbone interact with an
      electropositive band generated by lysines of the RBD. Nucleotides of the single
      stranded loop of hairpin 92 interact with the RBD, including the guanosine base
      of G2553, which forms three hydrogen bonds with the peptide backbone. A G2553U
      mutation reduces the RNA binding affinity by 2 orders of magnitude, confirming
      that G2553 is a sequence specificity determinant in RNA binding. Binding of the
      RBD to 23S rRNA in the late stages of ribosome subunit maturation would position
      the ATP-binding duplex destabilization fragment of the protein for interaction
      with rRNA in the peptidyl transferase cleft of the subunit, allowing it to "melt
      out" unstable secondary structures and allow proper folding.

PMID- 20673835
TI  - The neuroprotective effect of talipexole from paraquat-induced cell death in
      dopaminergic neuronal cells.
AB  - Talipexole is a non-ergot dopamine (DA) agonist that has been used in the
      treatment of Parkinson's disease. In the present study, we examined the effect of
      talipexole on paraquat (PQ)-induced N27 cell death and the intracellular pathways
      involved in this effect. Pretreatment of N27 cells with talipexole (1mM) resulted
      in significant protection against paraquat-induced cell death. In N27 cells,
      talipexole inhibited paraquat-induced apoptotic hallmarks such as cytochrome c
      release, caspase-3 activation, chromatin condensation and externalization of
      phosphatidilserine. Talipexole pretreatment prevents the reduction in the anti
      apoptotic Bcl-x(L) protein and increases in the pro-apoptotic form of Bak and p
      Bad, both induced by PQ. Finally, we also observed that talipexole abrogates the
      activation of cell death pathways JNK1/2 and p38 produced by PQ, and increases
      the phosphorylated (active) forms of the pro-survival pathways ERK1/2 and Akt.
      These results reveal that talipexole exerts a neuroprotective effect in a
      mesencephalic cell line exposed to the neurotoxin PQ, which is related to the
      etiology of Parkinson's disease.

PMID- 20673836
TI  - DARPins against a functional IgE epitope.
AB  - The monoclonal anti-IgE antibody omalizumab (Xolair is mostly used for the
      treatment of severe allergic asthma. However, the requirement of high doses and
      suboptimal cost-effectiveness limits the use of the treatment. Here we propose to
      use a new drug format based on non-immunoglobulin structures, potentially
      offering increased clinical efficacy while being more cost-effective. For this
      purpose, DARPinsTM (designed ankyrin repeat proteins) against the constant heavy
      chain region of IgE have been isolated. DARPins were binding to IgE with high
      specificity and affinities in the low nanomolar range. Selected DARPins
      antagonized the interaction between IgE and its high-affinity receptor in
      inhibition assays. Furthermore, anti-IgE DARPins were shown to inhibit
      proinflammatory mediator release from rat basophilic leukemia cells expressing
      human high-affinity IgE receptors with higher efficacy than the monoclonal anti
      IgE antibody omalizumab. DARPins may thus represent promising future drug
      candidates for the treatment of allergy.

PMID- 20673837
TI  - One-tube loop-mediated isothermal amplification combined with restriction
      endonuclease digestion and ELISA for colorimetric detection of resistance to
      isoniazid, ethambutol and streptomycin in Mycobacterium tuberculosis isolates.
AB  - In this study, we designed a simple and rapid colorimetric detection method, a
      one-tube loop-mediated isothermal amplification (LAMP)-PCR-hybridization
      restriction endonuclease-ELISA [one-tube LAMP-PCR-HY-RE-ELISA] system, to detect
      resistance to isoniazid, ethambutol and streptomycin in strains of Mycobacterium
      tuberculosis isolated from clinical specimens. The clinical performance of this
      method for detecting isoniazid-resistant, ethambutol-resistant and streptomycin
      resistant isolates of M. tuberculosis showed 98.9%, 94.3% and 93.8%,
      respectively. This assay is rapid and convenient that can be performed within one
      working day. One-tube LAMP-PCR-HY-RE-ELISA system was designed based on hot spot
      point mutations in target drug-resistant genes, using LAMP-PCR, hybridization,
      digestion with restriction endonuclease and colorimetric method of ELISA. In this
      study, LAMP assay was used to amplify DNA from drug-resistant M. tuberculosis,
      and ELISA was used for colorimetrical determination. This assay will be a useful
      tool for rapid diagnosis of mutant codons in strains of M. tuberculosis for
      isoniazid at katG 315 and katG 463, ethambutol at embB 306 and embB 497, and
      streptomycin at rpsL 43.

PMID- 20673839
TI  - Simultaneous detection of Ureaplasma parvum, Ureaplasma urealyticum, Mycoplasma
      genitalium and Mycoplasma hominis by fluorescence polarization.
AB  - A simple and practical method for simultaneous detection of Ureaplasma
      urealyticum (U. urealyticum), Ureaplasma parvum (U. parvum), Mycoplasma hominis
      (M. hominis) and Mycoplasma genitalium (M. genitalium) by fluorescence
      polarization (FP) assay has been developed. DNA of the 16S rRNA gene of U.
      urealyticum, U. parvum, M. genitalium and M. hominis was amplified using a
      forward primer and two reverse primers in an asymmetric PCR. Four probes labeled
      with different fluorophores were specific for U. urealyticum, U. parvum, M.
      hominis and M. genitalium, respectively. The probes hybridized with their target
      PCR products, and the hybridization increased the fluorescence polarization (FP)
      values. The pathogens were identified by the increased FP values. DNA extracted
      from 757 urethral samples was detected by the FP assay and the sequence method.
      The FP assay could detect co-infection more effectively than the sequence method
      did. The method presented in this study was expected to be extremely useful in
      clinic.

PMID- 20673838
TI  - Attenuation of bacterial virulence by quorum sensing-regulated lysis.
AB  - Genetically attenuated pathogenic bacteria have been extensively considered as
      vaccine candidates. However, insufficient attenuation has been a frequent
      limitation of this approach. Many pathogens use quorum sensing to escape host
      defense mechanism. Here, we hypothesized that quorum sensing can be manipulated
      to diminish pathogenesis. To test this hypothesis, we modified the quorum sensing
      circuitry of a live cholera vaccine strain to add a second layer of attenuation.
      Attenuation resulted from the expression of phage PhiX174 lysis gene E on a
      balanced lethal plasmid from the quorum sensing-regulated luxC promoter. For
      conditional expression of quorum sensing and positive selection in vivo, the host
      strain was deleted of its cqsA and thyA genes encoding cholera autoinducer 1 (CAI
      1) synthase and thymidylate synthase, respectively. A recombinant cqsA gene
      expressed from the cholera toxin (CT) promoter and an active thyA gene was
      provided in trans. The resulting strain expressed CAI-1 in AKI cultures (CT
      permissive condition) but not in LB medium. Additionally, it expressed elevated
      biofilm in LB medium compared to AKI conditions where CAI-1 is synthesized to
      repress biofilm formation. Induction of lysis gene E by quorum sensing restricted
      growth to a lower cell density in AKI medium, the suckling mouse intestine or LB
      supplemented with exogenous CAI-1. Microscopic examination revealed the presence
      of Vibrio cholerae ghost cells at high cell density. Lysis was accompanied by the
      release of intracellular beta-galactosidase to the culture medium. We conclude
      that it is possible to manipulate quorum sensing to attenuate a live vaccine
      vector and restrict its shedding to the environment and diminish its subsequent
      dissemination.

PMID- 20673840
TI  - In vivo growth of porcine reproductive and respiratory syndrome virus engineered
      nsp2 deletion mutants.
AB  - Prior studies on PRRSV strain VR-2332 non-structural protein 2 (nsp2) had shown
      that as much as 403 amino acids could be removed from the hypervariable region
      without losing virus viability in vitro. We utilized selected nsp2 deletion
      mutants to examine in vivo growth. Young swine (4 pigs/group; 5 control swine)
      were inoculated intramuscularly with one of 4 nsp2 deletion mutants (rDelta727
      813, rDelta543-726, rDelta324-523, rDelta324-726) or full-length recombinant
      virus (rVR-2332). Serum samples were collected on various days post-inoculation
      and analyzed by HerdChek* ELISA, PRRSV real time RT-PCR, gamma interferon (IFN
      gamma) ELISA, and nucleotide sequence analysis of the entire nsp2 coding region.
      Tracheobronchial lymph node weight compared to body weight was recorded for each
      animal and used as a clinical measurement of viral pathogenesis. Results showed
      that all deletion mutants grew less robustly than full-length recombinant virus,
      yet all but the large deletion virus (rDelta324-726) recovered to parental viral
      RNA levels by study end. Swine receiving the rDelta727-813 mutants had a
      significant decrease in lymph node enlargement compared to rVR-2332. While swine
      infection with rVR-2332 caused a rapid rise in serum IFN-gamma levels, the IFN
      gamma protein produced by infection with 3 of the 4 deletion mutant viruses was
      significantly reduced, perhaps due to differences in viral growth kinetics. The
      rDelta543-726 nsp2 mutant virus, although growth impaired, mimicked rVR-2332 in
      inducing a host serum IFN-gamma response but exhibited a 2-week delay. Targeted
      sequencing showed that all deletions were stable in the region coding for nsp2
      after one swine passage. The data suggested that the selected nsp2 deletion
      mutants were growth attenuated in swine, altered the induction of serum IFN
      gamma, an innate cytokine of unknown function in PRRSV clearance, and pointed to
      a domain that may influence tracheobronchial lymph node size.

PMID- 20673841
TI  - AMPA- and P2X7-receptor-mediated facilitation of [3H]D-aspartate release from
      nerve terminals isolated from the rat caudal brainstem.
AB  - Glutamate (GLU) plays a key role in the transmission and modulation of sensory
      input to the trigeminal caudal nuclei (TCN). In the present study, we
      investigated the regulation of previously taken-up [3H]D-aspartate ([3H]D-ASP)
      release from nerve terminals isolated from rat caudal brainstem, in particular
      from the zone containing the TCN. TCN neurons can be considered integrative relay
      neurons linking peripheral and central pain mechanisms. Understanding the
      mechanisms that control the release of GLU in this area could lead to more
      effective treatment of migraines and other types of pain associated with the
      trigeminal nerve. In isolated rat caudal brainstem synaptosomes, exposure to AMPA
      dose-dependently potentiated [K+](e)-stimulated release of [3H]D-ASP (maximum
      increase: 218+/-13.08%; EC(50): 1.60+/-0.08 MUM). This effect was inhibited by
      selective AMPA-receptor antagonists (competitive [NBQX] and non-competitive
      [GYKI52466]) but not by the kainate receptor subunit antagonists NS102 and ACET.
      AMPA-evoked responses were significantly enhanced by preventing AMPA receptor
      desensitization with cyclothiazide (10 MUM). Basal release of [3H]D-ASP was
      stimulated by millimolar concentrations of ATP (maximum increase: 197.80+/
      11.85%; EC(50): 545+/-3.15 MUM) and by the selective P2X7-receptor agonist
      benzoylbenzoyl-ATP. ATP also potentiated the release of [3H]D-ASP induced by
      depolarization. Its effect on basal [3H]D-ASP release was inhibited by the
      selective P2X7-receptor antagonist A-438079 and by the non-selective antagonist
      PPADS, but it was only partially suppressed by the ionotropic purinergic receptor
      antagonist TNP-ATP. Our findings demonstrate that glutamatergic nerve terminals
      in rat caudal brainstem express AMPA receptors that can facilitate [3H]D-ASP
      during terminal depolarization and P2X7 receptors that can also enhance this
      release under basal conditions.

PMID- 20673842
TI  - The influence of social support on cardiovascular responses during stressor
      anticipation and active coping.
AB  - This study investigated effects of different types of social support on
      cardiovascular reactivity during anticipation of, performance of and recovery
      from an evaluative speaking task. Thirty male and 30 female students were
      assigned to one of three social conditions: alone, mental activation of
      supportive ties, actual support transactions. Cardiovascular effects of social
      support were found to differ over task conditions and they were not
      unidirectional. During passive stressor anticipation, support conditions
      attenuated SBP reactivity, in particular mental activation of supportive ties.
      During active speech performance gender-specific support effects were observed.
      The alone condition elicited higher SBP reactivity in men compared to women,
      support conditions enhanced SBP reactivity in women and attenuated SBP reactivity
      in men resulting in comparable cardiovascular activation across gender groups.
      Drawing from research on active coping and energization gender-specific
      cardiovascular activation was attributed to differences in effort expenditure.

PMID- 20673843
TI  - Regulation of cell death in human fetal and adult ovaries--role of Bok and Bcl
      X(L).
AB  - Of eight million oocytes formed in fetal ovaries, only 400 are ovulated and the
      rest are degraded via apoptosis. Studies in rodents suggest an important role for
      Bok and Bcl-X(L) in ovarian apoptosis, but their expression patterns and roles in
      human ovaries are not well known. Protein expression of Bok and Bcl-X(L) as well
      as the death pathway effectors TNF and caspase-3 were determined in an important
      collection of samples consisting of human fetal and adult ovaries. A penetrant
      expression of Bok, Bcl-X(L), TNF and full length and cleaved caspase-3 were
      characterized in fetal ovaries, with specific patterns in oocytes and pre
      granulosa/granulosa cells. Bok and Bcl-X(L) were detected also in adult ovaries.
      Lentiviral shRNA delivery demonstrated that loss of Bok markedly reduces
      vulnerability to apoptosis and, conversely, loss of Bcl-X(L) increases apoptosis
      in human granulosa tumour cell line. The results suggest important roles for Bok
      and Bcl-X(L) in human ovarian development, follicle maturation and apoptosis.

PMID- 20673844
TI  - Anti-amnesic effect of Chong-Myung-Tang on scopolamine-induced memory impairments
      in mice.
AB  - AIM OF THE STUDY: Chong-Myung-Tang (CMT) consisted of Acorus gramineus Soland,
      Polygala tenuifolia Willdenow, and Poria cocos Wolf is one of the traditional
      Korean herbal medicines used for the therapy of learning and memory improvement.
      The present study was investigated the effect of CMT on learning and memory
      functions in SCOP-induced memory deficits mice. MATERIALS AND METHODS: The
      cognitive-enhancing effect of CMT on amnesic mice induced by SCOP was
      investigated by assessing the passive avoidance test and the Morris water maze
      test. In order to confirm the underlying mechanisms of memory enhancing effects
      of CMT, activities of AChE, choline acetyltransferase (ChAT), and antioxidant
      enzymes were measured. RESULTS: Administration of CMT significantly restored
      memory impairments induced by SCOP in the passive avoidance test and also reduced
      escape latency during trial sessions in the Morris water maze test. The increased
      AChE activity produced by SCOP was significantly inhibited by CMT. CMT
      significantly enhanced ChAT activity. Moreover, treatment with CMT to the amnesic
      mice induced by SCOP considerably decreased malondialdehyde levels and restored
      activities of superoxide dismutase and catalase to the control values.
      CONCLUSIONS: These results suggest that CMT may be useful for the cognitive
      improvement via regulation of cholinergic marker enzyme activities and the
      antioxidant defense system.

PMID- 20673845
TI  - Subtle white matter injury is common in term-born infants with a wide range of
      risks.
AB  - OBJECTIVES: Perinatal hypoxia-ischaemia affects cognitive outcomes of infants
      even when clinical symptoms were latent and intensive care was not required. We
      performed a retrospective analysis in a cohort of term infants who required
      intensive care (i) to investigate the incidence of abnormal white matter
      appearances on the magnetic resonance imaging obtained before 2 months corrected
      age, and (ii) to examine its relationships with other cerebral lesions, clinical
      backgrounds, and short-term outcome at 12 months. STUDY DESIGN: White matter
      appearances on T2-weighted imaging (T2WI) and fluid-attenuated inversion recovery
      imaging (FLAIR) were assessed in relationship with other cerebral lesions,
      clinical backgrounds, established white matter lesions on follow-up scans, and
      abbreviated developmental outcomes at 12 months in 150 term-born infants who were
      cared for at a tertiary neonatal intensive care unit with mixed indications for
      admission (positive pressure ventilation and intravenous inotropes required in
      38% and 49% of infants respectively). RESULTS: On T2WI and FLAIR, 14.0% and 41.3%
      of infants showed abnormal white matter intensities respectively, which were both
      related with lesions in the internal capsule and deep grey matter. Abnormal T2WI
      appearances were correlated with low Apgar scores and low blood base-excess
      whereas abnormal FLAIR appearances were associated with younger corrected age at
      scan. Follow-up studies in a cohort of infants revealed that abnormal white
      matter intensities further correlated with chronic long-T2 lesions after 8 months
      corrected age (n=40) and severe neuro-developmental disability at 12 months
      (n=104). CONCLUSIONS: Abnormal white matter intensities were associated with
      pathological clinical variables. White matter injury may not be a specific form
      of cerebral damage in preterm infants. For the precise evaluation of newborn
      brain imaging, it may be beneficial to account for corrected age even in term
      infants.

PMID- 20673846
TI  - Differential treatment regimen-related effects of cannabinoids on D1 and D2
      receptors in adolescent and adult rat brain.
AB  - Animal studies suggest differential effects of cannabinoids on dopamine-related
      behaviours in adolescence and adulthood however few studies have investigated the
      underlying neurochemical effects of cannabinoids during adolescence. The aim of
      the present study was to compare the effects of treatment with the synthetic
      cannabinoid, HU210, on dopamine receptor density in adolescent and adult rats.
      Adolescent (postnatal day (PND) 35) and adult (PND 70) rats received a single
      dose of 100MUg/kg HU210 or 25, 50 or 100MUg/kg HU210 for 4 or 14 days. Dopamine
      D1 receptor (D1R) or D2 receptor (D2R) density was measured in the medial and
      lateral (CPUL) caudate putamen, nucleus accumbens, olfactory tubercle (TU) and
      substantia nigra (D1R only) using in vitro autoradiography. D1R and D2R densities
      were 1.6-1.7- and 1.1-1.4-fold higher respectively in adolescent control rats
      compared to adults. In adult rats, D1R density was increased by 1.2- and 1.3-fold
      (p<0.05) in CPUL and TU respectively compared to controls, after 14 days of HU210
      treatment. A significant overall effect of treatment (p<0.05) on D2R density was
      also observed in adults after the single dose and 4 and 14 days administration of
      HU210. In adolescents, an overall effect of treatment on D1R density after a
      single exposure to HU210 was seen (p=0.0026) but no changes in D1R or D2R
      densities were observed in other treatment groups. These results suggest that the
      adolescent rat brain does not display the same compensatory mechanisms activated
      in the adult brain following cannabinoid treatment.

PMID- 20673847
TI  - Cytotoxic potency of H2O2 in cell cultures: impact of cell concentration and
      exposure time.
AB  - Using C6 glioma cells in this study we investigated in detail how exposure time
      and cell concentration affect the cytotoxic potency of H(2)O(2) in vitro. Median
      cytotoxic concentrations (EC(50)) decreased from 500 to 30 MUM with increasing
      incubation time from 1 to 24h. Twenty-four hours proved to be sufficient to
      determine incipient cytotoxic concentrations of H(2)O(2). The incipient EC(50)
      values were linearly related to the cell concentration. A cell concentration
      independent median cytotoxic cell dose (ED(50)) of 430 nmol/mg cell protein or
      860 nmol/10(7) cells was derived. Median cytotoxic H(2)O(2) concentrations were
      completely eliminated from the culture medium at a rate proportional to both the
      H(2)O(2) and the cell concentrations. In contrast to EC(50) values the
      corresponding areas under the concentration versus time curve (AUC) were
      independent of the cell concentration and amounted to 1800 MUM*min. With
      decreasing cell concentration the H(2)O(2) elimination decelerates and, thus,
      exposure to H(2)O(2) applied as a bolus approaches a continuous exposure to a
      steady H(2)O(2) concentration. Taken together, our results indicate that the
      cytotoxic potency of H(2)O(2) administered to cultured cells as a bolus is
      characterized by the AUC, which depends on its initial concentration, the ability
      of the cells to eliminate H(2)O(2), and the cell concentration. We recommend
      expressing the toxic potency of H(2)O(2) in vitro by the incipient toxic cell
      dose (e.g., nmol H(2)O(2)/mg cell protein or nmol H(2)O(2)/10(7) cells), in
      particular for comparative purposes.

PMID- 20673848
TI  - Progesterone induction of chondroitin sulfate proteoglycan aggrecan expression in
      human endometrial epithelial cells.
AB  - Chondroitin sulfate (CS) is the most abundant glycosaminoglycan species in the
      human endometrium, but the expression profile of CS proteoglycans (PGs) in this
      mucosal tissue remains fully undetermined. In this study, we aimed to clarify the
      expression of CSPGs including aggrecan, neurocan, melanoma-associated CSPG,
      neuroglycan C, and brevican in the human cycling endometrium. By reverse
      transcription-polymerase chain reaction, the gene transcripts for aggrecan core
      protein were detected in all samples examined, while other CSPGs were not.
      Western blotting showed the immunoreactivity for aggrecan core protein at
      approximately 370 kDa size after enzymatic digestion of CS-A and CS-C side
      chains. The expression level of aggrecan core protein was significantly higher in
      the secretory phase than in the proliferative phase. The immunostaining for
      aggrecan was detected in the endometrial microvascular endothelium throughout the
      menstrual cycle. The immunostaining in the glandular epithelium was faint during
      the proliferative and early secretory phase, but distinct during the mid-to-late
      secretory phase. Progesterone, but not 17beta-estradiol, induced aggrecan core
      protein expression in cultured endometrial epithelial cells. The endometrial
      expression pattern of aggrecan was distinct from that of other known CSPGs,
      suggesting the unique role of this proteoglycan at the implantation site.

PMID- 20673849
TI  - Partition-based mass clustering of tractography streamlines.
AB  - We describe a novel scalable clustering framework for streamlines obtained from
      diffusion tractography. Clustering is an attractive means of segmenting a large
      set of streamlines into anatomically relevant bundles. For most existing methods,
      however, the large datasets produced in high resolution or multiple subject
      studies are problematical. To achieve good scalability, our method repeatedly
      divides the data into subsets, which are then partitioned using hierarchical
      clustering. A final partition is obtained by recombining the subsets. In
      addition, the recombination scheme provides a consistency measure for cluster
      assignment of individual streamlines, which is used to clean up the final result.
      The clusters have good anatomical plausibility and we show that three clusters
      corresponding to the three known segments of the arcuate fasciculus show
      excellent agreement with literature. A major advantage of the method is the fact
      that it can find clusters in datasets of essentially arbitrary size. This fact is
      exploited to find consistent clusters in concatenated tractography data from
      multiple subjects. We expect the identification of bundles across subjects to be
      an important application of the method.

PMID- 20673850
TI  - Skin and urine pentosidine weakly correlate with joint damage in a cohort of
      patients with early signs of osteoarthritis (CHECK).
AB  - OBJECTIVES: Age-related changes in articular cartilage are likely to play a role
      in the aetiology of osteoarthritis (OA). One of the major age-related changes in
      cartilage is the accumulation of advanced-glycation-endproducts (AGEs). Since,
      cartilage tissue is not readily available from patients for studying AGE levels,
      alternative approaches such as analyzing skin and urine are needed to study the
      role of cartilage AGE levels in OA. METHODS: Paired human skin and cartilage
      samples were obtained post mortem. Paired skin and urine samples were obtained
      from the CHECK cohort (early OA patients). Pentosidine levels were measured by
      high-performance liquid chromatography (HPLC). As marker of cumulative cartilage
      damage X-rays of both knees and hips were scored. Urinary CTXII (uCTXII) levels
      were measured, to assess current cartilage breakdown. RESULTS: Cartilage and skin
      pentosidine correlate well (R=0.473, P=0.05). Skin pentosidine was higher in mild
      (summed (Kellgren & Lawrence K&L) over four large joints >=4) compared to no
      (summed K&L<=3) radiographic OA (P=0.007). Urinary pentosidine was not different
      between these two groups. Skin pentosidine levels were not related to cartilage
      breakdown (highest vs lowest tertile of uCTXII). Urinary pentosidine, however,
      was higher in the highest compared to the lowest uCTXII tertile (P=0.009).
      Multiple regression analysis showed age to be the only predictor of the summed
      K&L score and age, creatinine clearance and urinary pentosidine as predictors of
      uCTXII. CONCLUSION: The higher skin and urinary pentosidine levels in those with
      mild compared to no radiographic joint damage and low vs high cartilage breakdown
      respectively suggest that AGEs may contribute to disease susceptibility and/or
      progression. However, relations are weak and cannot be used as surrogate markers
      of severity of OA.

PMID- 20673852
TI  - On the second role of the random element in minimization.
AB  - Although the main reason for adding a random element at every step of
      minimization procedure is to reduce predictability of the upcoming treatment
      assignments in single-center open-label trials, there is another reason for its
      use, applicable to double-blind trials. Adding the random element at every
      allocation step allows one to avoid a fully deterministic sequence of treatment
      assignments for sequences of covariates for which at every allocation step one of
      the treatments leads to a better balance in covariates than all other treatments.
      An example of such a sequence is provided in this communication.

PMID- 20673851
TI  - Non-stereo-selective cytosolic human brain tissue 3-ketosteroid reductase is
      refractory to inhibition by AKR1C inhibitors.
AB  - Cerebral 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD) activity was suggested
      to be responsible for the local directed formation of neuroactive 5alpha,3alpha
      tetrahydrosteroids (5alpha,3alpha-THSs) from 5alpha-dihydrosteroids. We show for
      the first time that within human brain tissue 5alpha-dihydroprogesterone and
      5alpha-dihydrotestosterone are converted via non-stereo-selective 3-ketosteroid
      reductase activity to produce the respective 5alpha,3alpha-THSs and 5alpha,3beta
      THSs. Apart from this, we prove that within the human temporal lobe and limbic
      system cytochrome P450c17 and 3beta-HSD/Delta(5-4) ketosteroid isomerase are not
      expressed. Thus, it appears that these brain regions are unable to conduct de
      novo biosynthesis of Delta(4)-3-ketosteroids from Delta(5)-3beta-hydroxysteroids.
      Consequently, the local formation of THSs will depend on the uptake of
      circulating Delta(4)-3-ketosteroids such as progesterone and testosterone. 3alpha
      and 3beta-HSD activity were (i) equally enriched in the cytosol, (ii) showed
      equal distribution between cerebral neocortex and subcortical white matter
      without sex- or age-dependency, (iii) demonstrated a strong and significant
      positive correlation when comparing 46 different specimens and (iv) exhibited
      similar sensitivities to different inhibitors of enzyme activity. These findings
      led to the assumption that cerebral 3-ketosteroid reductase activity might be
      catalyzed by a single enzyme and is possibly attributed to the expression of a
      soluble AKR1C aldo-keto reductase. AKR1Cs are known to act as non-stereo
      selective 3-ketosteroid reductases; low AKR1C mRNA expression was detected.
      However, the cerebral 3-ketosteroid reductase was clearly refractory to
      inhibition by AKR1C inhibitors indicating the expression of a currently
      unidentified enzyme. Its lack of stereo-selectivity is of physiological
      significance, since only 5alpha,3alpha-THSs enhance the effect of GABA on the
      GABA(A) receptor, whereas 5alpha,3beta-THSs are antagonists.

PMID- 20673853
TI  - Plagiarism: the plague of digital media?

PMID- 20673854
TI  - Neck strength recovery after a single bout of specific strengthening exercise.
AB  - OBJECTIVE: To determine the level of neck strength decrement and the rate of
      strength recovery of the neck muscles after a single bout of specific neck
      conditioning exercise in both males and females. HYPOTHESIS: A decrement in neck
      strength may be evident after a bout of strengthening exercise. DESIGN:
      Intervention study with pre-and-post design. SETTING: Biomechanics laboratory.
      PARTICIPANTS: Twenty healthy participants (10 male and 10 female, mean +/-
      standard deviation age 22 +/- 1.2 years). MAIN OUTCOME MEASURES: Participants
      performed a single bout of neck strengthening exercise. Neck strength testing
      using an isokinetic dynamometer was performed pre and at five time points (1 h,
      one, three, five and seven days) post-exercise to assess the level of neck
      strength decrement and neck strength recovery rate from pre-exercise levels.
      RESULTS: Statistically significant (p > or = 0.036) decreases in neck extension
      strength were recorded in all participants 1 h and one day post-exercise. The
      level of neck extension strength returned to pre-exercise levels three days post
      exercise and surpassed pre-exercise levels five and seven days post-exercise. The
      male participants' neck flexion strength decrement and recovery followed a
      similar pattern to that displayed in neck extension but more variability in neck
      flexion strength recovery rates were recorded in the female participants in this
      study. CONCLUSION: The consistent strength recovery times for the male
      participants recorded in this study idealise the prescription of neck
      strengthening exercises in a periodised fashion. More investigation needs to be
      instigated for the female neck musculature as consistent strength recovery rates
      were not identified in this study.

PMID- 20673855
TI  - Correlation of three different knee joint position sense measures.
AB  - OBJECTIVE: The purpose of this study was to investigate correlation during
      concurrent measurement among three knee joint position sense (JPS) measures in
      sitting position and between two measures in standing position. METHODS:
      Isokinetic dynamometer, electrogoniometer, and two dimensional (2D) video
      analysis were used for measuring knee JPS. The JPS was measured both in sitting
      and standing positions. All three measures were employed concurrently to measure
      knee JPS in sitting position; however, only the electrogoniometer and 2D video
      analysis were concurrently used in the standing position. The knee JPS was
      recorded in sitting position at 15 degrees, 30 degrees, and 45 degrees and in
      standing at high, mid and low knee flexion positions. RESULTS: The results of the
      study suggest excellent correlation (0.94-0.98) between the electrogoniometer and
      2D video analysis measures in standing position. In sitting position, good to
      excellent correlation (0.63-0.92) was found between the isokinetic dynamometer
      and electrogoniometer; however, fair to good correlation was found between 2D
      video analysis and either of the two measures (electrogoniometer [0.52-0.57] and
      isokinetic dynamometer [0.41-0.63]. CONCLUSION: Either 2D video or an
      electrogoniometer may be used to measure JPS in standing position; however, in
      sitting position 2D video should not be used if the camera is required to be
      placed at 10 degrees from the plane of motion.

PMID- 20673856
TI  - Warming-up before sporting activity improves knee position sense.
AB  - OBJECTIVE: To evaluate the effects of a warm-up program on knee joint position
      sense in karatekas. DESIGN: Repeated measures design. SETTING: Research
      laboratory. PARTICIPANTS: Ten young amateur karatekas (17.6 +/- 4.0 years of
      age). MAIN OUTCOME MEASURES: Knee joint position sense evaluated before and
      immediately after a warm-up program through active repositioning in open kinetic
      chain (OKC) and closed kinetic chain (CKC). RESULTS: At baseline testing no
      differences were observed between OKC and CKC in absolute (4.1 +/- 1.6 degrees
      vs. 3.4 +/- 2.0 degrees) and relative angular errors (2.4 +/- 3.4 degrees vs. 2.1
      +/- 3.5 degrees). After the warm-up program, a significant decrease in absolute
      angular error was observed only in CKC (from 3.4 +/- 2.0 degrees to 1.8 +/- 0.5,
      p < 0.05). Additionally, in CKC the subjects reduced the relative angular error
      to approximately zero (from 2.1 +/- 3.5 degrees to -0.01 +/- 1.6 degrees) and
      decreased the variability of the responses, expressed by the decrease in standard
      deviation of the relative errors. CONCLUSIONS: The warm-up program enhanced knee
      joint position sense only in CKC. Since no effects were detected in OKC, the
      evaluation of the effects of warm-up on knee joint position sense using merely an
      OKC technique would underestimate the valuable role of warm-up.

PMID- 20673857
TI  - Clinical massage and modified Proprioceptive Neuromuscular Facilitation
      stretching in males with latent myofascial trigger points.
AB  - OBJECTIVES: To determine the immediate effects of modified Proprioceptive
      Neuromuscular Facilitation (PNF) stretching (group I) versus Myofascial Trigger
      Point (MTrP) therapy plus modified PNF stretching (group II) in comparison to a
      control group receiving no treatment. DESIGN: Randomized, assessor-blind, (3 x 4)
      mixed-model repeated measures. SETTING: University laboratory. PARTICIPANTS:
      Thirty physically active males with tight hamstrings and at least one latent MTrP
      on muscles innervated by the lumbosacral, sciatic, tibial and common peroneal
      nerves. MAIN OUTCOME MEASURES: Knee range of motion (ROM), stretch perception,
      pressure pain threshold (PPT) and subjective pain intensity. Outcomes were
      evaluated at baseline, immediately after treatment, at 10 and 30 min. RESULTS:
      Significant changes over time occurred for group II in all outcomes (p < or =
      0.001). Group II also showed lower pain intensity scores than group I immediately
      post-treatment (p = 0.045) and a strong clinical effect over group I in ROM at
      all follow-ups (effect sizes = 0.9-1.0, p < or = 0.05). Other differences were
      found between both stretching groups as compared to the control group (p < or =
      0.05). CONCLUSION: The results indicate immediate pre- to post-treatment benefits
      from MTrP therapy combined with modified PNF stretching in young and physically
      active males with latent MTrPs.

PMID- 20673858
TI  - Short and mid-term results of a comprehensive treatment program for longstanding
      adductor-related groin pain in athletes: a case series.
AB  - OBJECTIVE: To evaluate short and mid-term results of active physical therapy in
      athletes with longstanding groin pain. DESIGN: Case series. SETTING: Primary care
      physical therapy practice. PARTICIPANTS: A total of 44 athletes suffering
      longstanding adductor-related groin pain. INTERVENTION: A combination of passive
      (joint mobilization) and active (exercises) physical therapy interventions. MAIN
      OUTCOME MEASUREMENTS: Return to (the same level of) sports, restriction in
      sports, and recurrence. RESULTS: Directly after treatment, return to the same
      level and type of sport was successful in 38 athletes (86%), and without symptoms
      in 34 athletes (77%). At 6.5-51 months follow up, 10/38 (26%) of those that
      returned to sports had experienced a relapse; 22 (50%) athletes were able to
      participate in sports without any restrictions at the mid-term follow-up.
      CONCLUSIONS: For athletes with longstanding groin pain, short term results of
      physical therapy seem positive, whereas mid-term results are moderately positive.
      The risk for recurrence is high.

PMID- 20673859
TI  - Long-term visual associations affect attentional guidance.
AB  - When observers perform a visual search task, they are assumed to adopt an
      attentional set for what they are looking for. The present experiment
      investigates the influence of long-term visual memory associations on this
      attentional set. On each trial, observers were asked to search a display for a
      grayscale version of a known traffic sign. On each trial, a distractor sign was
      drawn in full color. This color could either be related or unrelated to the
      target sign. Distractors interfered more with search when their color was related
      (e.g. red when the target was a stop sign), implying that long-term color
      associations resulted in inadvertent attentional guidance, even though color was
      irrelevant to the task. The results add to the growing body of evidence that long
      term memory representations automatically affect attentional orienting.

PMID- 20673860
TI  - Ultrastructural consideration on the nature, sol and gel, of the aqueous
      cytoplasm in embedment-free section electron microscopy.
AB  - TEM of any in situ cells in embedment-free sections--regardless of specimen
      fixation methods--clearly shows strand-lattices occupying the cytoplasmic matrix.
      The cytoplasmic matrix is assumed to be a site of soluble proteins; however, it
      appears indistinct as conventional TEM cannot target it. Strand-lattices similar
      to the cytoplasmic ones are duplicated in bovine serum albumin as well as solated
      gelatin fixed at warm temperatures and at appropriate concentrations, while
      lattices from gelatin gelated by cooling before fixation are much more compact
      than those from solated gelatin at a given concentration. Based on the finding of
      the in vitro proteins, a new interpretation of cell ultrastructures in embedment
      free section TEM is proposed: first, differences in the compactness of
      cytoplasmic lattices represent those in the protein concentration in the
      cytoplasmic matrix; second, when loose and compact lattices are contiguous within
      a cell, the cytoplasmic matrix domain occupied by the compact lattice is in a gel
      state while the remaining domain of the same cell is in a sol state. The
      explanation for the states of the gel and sol based on the lattice-compactness is
      applicable to changes in the lattice-compactness of the cytoplasmic matrix of
      neurohypophyseal axons under intense secretion.

PMID- 20673861
TI  - A new semi-empirical kinetic method for the determination of ion exchange
      constants for the counterions of cationic micelles.
AB  - A new method, based upon semi-empirical kinetic approach, for the determination
      of ion exchange constant for ion exchange processes occurring between counterions
      at the cationic micellar surface is described in this review article. Basically,
      the method involves a reaction kinetic probe which gives observed pseudo-first
      order rate constants (k(obs)) for a nucleophilic substitution reaction between
      the nonionic and anionic reactants (R and S) in the presence of a constant
      concentration of both reactants as well as cationic micelles and varying
      concentrations of an inert inorganic or organic salt (MX). The observed data
      (k(obs), versus [MX]) fit satisfactorily (in terms of residual errors) to an
      empirical equation which could be derived from an equation explaining the
      mechanism of the reaction of the kinetic probe in terms of pseudophase micellar
      (PM) model coupled with another empirical equation. This (another) empirical
      equation explains the effect of [MX] on cationic micellar binding constant (K(S))
      of the anionic reactant (say S) and gives an empirical constant, K(X/S). The
      magnitude of K(X/S) is the measure of the ability of X(-) to expel S(-) from a
      cationic micellar pseudophase to the bulk aqueous phase through ion exchange X(
      )/S(-). The values of K(X/S) and K(Y/S) (where Y(-) is another inert counterion)
      give the ion exchange constant, K(X)(Y) (=K(X)/K(Y) where K(X) and K(Y) represent
      cationic micellar binding constants of X(-) and Y(-), respectively). The
      suitability of this method is demonstrated by the use of three different reaction
      kinetic probes and various MX.

PMID- 20673862
TI  - Mutations in IMPG2, encoding interphotoreceptor matrix proteoglycan 2, cause
      autosomal-recessive retinitis pigmentosa.
AB  - Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal diseases
      caused by progressive degeneration of the photoreceptor cells. Using autozygosity
      mapping, we identified two families, each with three affected siblings sharing
      large overlapping homozygous regions that harbored the IMPG2 gene on chromosome
      3. Sequence analysis of IMPG2 in the two index cases revealed homozygous
      mutations cosegregating with the disease in the respective families: three
      affected siblings of Iraqi Jewish ancestry displayed a nonsense mutation, and a
      Dutch family displayed a 1.8 kb genomic deletion that removes exon 9 and results
      in the absence of seven amino acids in a conserved SEA domain of the IMPG2
      protein. Transient transfection of COS-1 cells showed that a construct expressing
      the wild-type SEA domain is properly targeted to the plasma membrane, whereas the
      mutant lacking the seven amino acids appears to be retained in the endoplasmic
      reticulum. Mutation analysis in ten additional index cases that were of Dutch,
      Israeli, Italian, and Pakistani origin and had homozygous regions encompassing
      IMPG2 revealed five additional mutations; four nonsense mutations and one
      missense mutation affecting a highly conserved phenylalanine residue. Most
      patients with IMPG2 mutations showed an early-onset form of RP with progressive
      visual-field loss and deterioration of visual acuity. The patient with the
      missense mutation, however, was diagnosed with maculopathy. The IMPG2 gene
      encodes the interphotoreceptor matrix proteoglycan IMPG2, which is a constituent
      of the interphotoreceptor matrix. Our data therefore show that mutations in a
      structural component of the interphotoreceptor matrix can cause arRP.

PMID- 20673863
TI  - Distinct effects of allelic NFIX mutations on nonsense-mediated mRNA decay
      engender either a Sotos-like or a Marshall-Smith syndrome.
AB  - By using a combination of array comparative genomic hybridization and a candidate
      gene approach, we identified nuclear factor I/X (NFIX) deletions or nonsense
      mutation in three sporadic cases of a Sotos-like overgrowth syndrome with
      advanced bone age, macrocephaly, developmental delay, scoliosis, and unusual
      facies. Unlike the aforementioned human syndrome, Nfix-deficient mice are unable
      to gain weight and die in the first 3 postnatal weeks, while they also present
      with a spinal deformation and decreased bone mineralization. These features
      prompted us to consider NFIX as a candidate gene for Marshall-Smith syndrome
      (MSS), a severe malformation syndrome characterized by failure to thrive,
      respiratory insufficiency, accelerated osseous maturation, kyphoscoliosis,
      osteopenia, and unusual facies. Distinct frameshift and splice NFIX mutations
      that escaped nonsense-mediated mRNA decay (NMD) were identified in nine MSS
      subjects. NFIX belongs to the Nuclear factor one (NFI) family of transcription
      factors, but its specific function is presently unknown. We demonstrate that NFIX
      is normally expressed prenatally during human brain development and
      skeletogenesis. These findings demonstrate that allelic NFIX mutations trigger
      distinct phenotypes, depending specifically on their impact on NMD.

PMID- 20673864
TI  - Mutations in the DBP-deficiency protein HSD17B4 cause ovarian dysgenesis, hearing
      loss, and ataxia of Perrault Syndrome.
AB  - Perrault syndrome is a recessive disorder characterized by ovarian dysgenesis in
      females, sensorineural deafness in both males and females, and in some patients,
      neurological manifestations. No genes for Perrault syndrome have heretofore been
      identified. A small family of mixed European ancestry includes two sisters with
      well-characterized Perrault syndrome. Whole-exome sequencing of genomic DNA from
      one of these sisters revealed exactly one gene with two rare functional variants:
      HSD17B4, which encodes 17beta-hydroxysteroid dehydrogenase type 4 (HSD17B4), also
      known as D-bifunctional protein (DBP). HSD17B4/DBP is a multifunctional
      peroxisomal enzyme involved in fatty acid beta-oxidation and steroid metabolism.
      Both sisters are compound heterozygotes for HSD17B4 c.650A>G (p.Y217C) (maternal
      allele) and HSB17B4 c.1704T>A (p.Y568X) (paternal allele). The missense mutation
      is predicted by structural analysis to destabilize the HSD17B4 dehydrogenase
      domain. The nonsense mutation leads to very low levels of HSD17B4 transcript.
      Expression of mutant HSD17B4 protein in a compound heterozygote was severely
      reduced. Mutations in HSD17B4 are known to cause DBP deficiency, an autosomal
      recessive disorder of peroxisomal fatty acid beta-oxidation that is generally
      fatal within the first two years of life. No females with DBP deficiency
      surviving past puberty have been reported, and ovarian dysgenesis has not
      previously been associated with this illness. Six other families with Perrault
      syndrome have wild-type sequences of HSD17B4. These results indicate that
      Perrault syndrome and DBP deficiency overlap clinically; that Perrault syndrome
      is genetically heterogeneous; that DBP deficiency may be underdiagnosed; and that
      whole-exome sequencing can reveal critical genes in small, nonconsanguineous
      families.

PMID- 20673865
TI  - A palindrome-mediated recurrent translocation with 3:1 meiotic nondisjunction:
      the t(8;22)(q24.13;q11.21).
AB  - Palindrome-mediated genomic instability has been associated with chromosomal
      translocations, including the recurrent t(11;22)(q23;q11). We report a syndrome
      characterized by extremity anomalies, mild dysmorphia, and intellectual
      impairment caused by 3:1 meiotic segregation of a previously unrecognized
      recurrent palindrome-mediated rearrangement, the t(8;22)(q24.13;q11.21). There
      are at least ten prior reports of this translocation, and nearly identical PATRR8
      and PATRR22 breakpoints were validated in several of these published cases. PCR
      analysis of sperm DNA from healthy males indicates that the t(8;22) arises de
      novo during gametogenesis in some, but not all, individuals. Furthermore,
      demonstration that de novo PATRR8-to-PATRR11 translocations occur in sperm
      suggests that palindrome-mediated translocation is a universal mechanism
      producing chromosomal rearrangements.

PMID- 20673866
TI  - Anesthesia complications during scheduled cesarean delivery for morbidly obese
      women.
AB  - OBJECTIVE: We sought to estimate the morbidity associated with regional
      anesthesia in morbidly obese women undergoing scheduled cesarean delivery. STUDY
      DESIGN: This was a retrospective cohort study of women undergoing elective
      scheduled cesarean delivery from September 2004 through December 2008. RESULTS: A
      total of 142 morbidly obese, 251 overweight and obese, and 185 normal-weight
      women met inclusion criteria. Differences between groups were identified
      regarding: complicated placement (5.6%, 2.8%, and 0%, respectively; P = .007),
      failure to establish (2%, 0%, and 0%, respectively; P = .047), and insufficient
      duration (4%, 0%, and 0%, respectively; P = .02) of regional anesthesia. The
      groups differed in the frequency of general anesthesia (6%, 0%, and 0%,
      respectively; P = .003), intraoperative hypotension (3%, 0%, and 0%,
      respectively; P = .01), and overall anesthetic complications (8.4%, 0%, and 0%,
      respectively; P < .0001). Prepregnancy body mass index > or = 40 kg/m(2)
      (receiver operating characteristic area under the curve, 0.856; positive
      likelihood ratio, 4.0) and delivery body mass index > or = 45 kg/m(2) (receiver
      operating characteristic area under the curve, 0.877; positive likelihood ratio,
      4.1) were predictive of anesthetic complications. CONCLUSION: Morbidly obese
      women have significant risk for anesthesia complications during cesarean
      delivery.

PMID- 20673867
TI  - The maternal body mass index: a strong association with delivery route.
AB  - OBJECTIVE: We sought to assess body mass index (BMI) effect on cesarean risk
      during labor. STUDY DESIGN: The Consortium on Safe Labor collected electronic
      data from 228,668 deliveries. Women with singletons > or = 37 weeks and known BMI
      at labor admission were analyzed in this cohort study. Regression analysis
      generated relative risks for cesarean stratifying for parity and prior cesarean
      while controlling for covariates. RESULTS: Of the 124,389 women, 14.0% had
      cesareans. Cesareans increased with increasing BMI for nulliparas and multiparas
      with and without a prior cesarean. Repeat cesareans were performed in > 50% of
      laboring women with a BMI > 40 kg/m(2). The risk for cesarean increased as BMI
      increased for all subgroups, P < .001. The risk for cesarean increased by 5%, 2%,
      and 5% for nulliparas and multiparas with and without a prior cesarean,
      respectively, for each 1-kg/m(2) increase in BMI. CONCLUSION: Admission BMI is
      significantly associated with delivery route in term laboring women. Parity and
      prior cesarean are other important predictors.

PMID- 20673869
TI  - Inhibition of Streptococcus mutans adherence and biofilm formation using
      analogues of the SspB peptide.
AB  - OBJECTIVE: Streptococcus gordonii is a pioneer colonizer of the enamel salivary
      pellicle that forms biofilm on the tooth surfaces. Recent reports show the
      surface protein analogue peptide {400 (T) of SspB 390-402 is substituted to K
      forming SspB (390-T400K-402)} from S. gordonii interacts strongly with salivary
      receptors to cariogenic bacteria, Streptococcus mutans. To characterize the
      analogue peptide biological activities, we investigated its binding and
      inhibiting effects, and the role of its amino acid moities. METHODS: We measured
      binding activity of analogue peptides to salivary components using the BIAcore
      assay; assayed inhibition activities of peptides for bacterial binding and growth
      on saliva-coated hydroxyapatite beads (s-HA); and describe the peptides
      interfering with biofilm formation of S. mutans on polystyrene surfaces. RESULTS:
      The SspB (390-T400K-402 and -401) peptides significantly bound with salivary
      components and inhibited the binding of S. mutans and S. gordonii to s-HA without
      bactericidal activity; but did not inhibit binding of Streptococcus mitis, a
      beneficial commensal. Further, the lack of D and E-L at position 390 and 401-402
      in the peptide, and substituted peptide SspB (D390H- or D390K-T400K-402) did not
      bind to salivary components or inhibit binding of S. mutans. The SspB (390-T400K
      402) peptide inhibited biofilm formation on salivary components-coated
      polystyrene surfaces in absence of conditioned planktonic cells. CONCLUSIONS: We
      found constructing the peptide to include positions 390(D), 400(K) and 401(E),
      two surface positive and negative connective charges, and at least 12 amino acids
      are required to bind salivary components and inhibit the binding of S. mutans and
      S. gordonii.

PMID- 20673870
TI  - Assaultive violence and the risk of posttraumatic stress disorder following a
      subsequent trauma.
AB  - Breslau, Peterson, and Shultz (2008) reported that prior trauma alone, in the
      absence of PTSD, did not predict an increased PTSD risk, relative to no prior
      trauma. Only prior trauma that resulted in PTSD predicted an increased PTSD risk
      following a subsequent trauma. Recently, Cougle, Resnick, and Kilpatrick (2009)
      proposed that the effect of prior trauma might vary by type of prior trauma, a
      possibility not considered in Breslau et al. They report that childhood sexual or
      physical assault, in the absence of PTSD, increased the PTSD risk following a
      subsequent trauma. This report examines the PTSD effects of prior assaultive
      violence, using data from Breslau et al. (1998). The study assessed PTSD in
      relation to up to three events. Analysis was performed on the subset with PTSD
      assessment for two distinct events, the earliest trauma and a subsequent trauma
      (n=967), using as reference persons with no prior trauma (n=972). Neither prior
      assaultive violence nor other prior traumas, in the absence of PTSD, influenced
      the subsequent risk of PTSD. In contrast, prior PTSD increased considerably the
      PTSD risk of a subsequent trauma. The limitations in Cougle et al. (2009) and in
      this study and future research directions are discussed.

PMID- 20673868
TI  - A genetic association study of maternal and fetal candidate genes that predispose
      to preterm prelabor rupture of membranes (PROM).
AB  - OBJECTIVE: We sought to determine whether maternal/fetal single-nucleotide
      polymorphisms (SNPs) in candidate genes are associated with preterm prelabor
      rupture of membranes (pPROM). STUDY DESIGN: A case-control study was conducted in
      patients with pPROM (225 mothers and 155 fetuses) and 599 mothers and 628 fetuses
      with a normal pregnancy; 190 candidate genes and 775 SNPs were studied. Single
      locus/haplotype association analyses were performed; false discovery rate was
      used to correct for multiple testing (q* = 0.15). RESULTS: First, a SNP in tissue
      inhibitor of metalloproteinase 2 in mothers was significantly associated with
      pPROM (odds ratio, 2.12; 95% confidence interval, 1.47-3.07; P = .000068), and
      this association remained significant after correction for multiple comparisons.
      Second, haplotypes for Alpha 3 type IV collagen isoform precursor in the mother
      were associated with pPROM (global P = .003). Third, multilocus analysis
      identified a 3-locus model, which included maternal SNPs in collagen type I alpha
      2, defensin alpha 5 gene, and endothelin 1. CONCLUSION: DNA variants in a
      maternal gene involved in extracellular matrix metabolism doubled the risk of
      pPROM.

PMID- 20673871
TI  - Changed relative to what? Housekeeping genes and normalization strategies in
      human brain gene expression studies.
AB  - Many studies in biological psychiatry compare the abundance of individual
      messenger RNAs between cases and control subjects or, more recently, between
      genotype groups. Most utilize some form of normalization procedure, usually
      expressing the transcript(s) of interest relative to that of a housekeeping gene
      or genes (also called reference genes), to overcome various sources of
      experimental error. Indeed, normalization is such a standard procedure that its
      purpose, principles, and limitations are sometimes overlooked, and some papers
      lack sufficient information as to its implementation. Here, we review the
      rationales for normalization and argue that in well-conducted psychiatric gene
      expression studies using human brain tissue, it is reducing intersubject
      variability rather than experimental error that is the major benefit of
      normalization. We also review the conceptual and empirical basis for the category
      of housekeeping genes-i.e., genes with a ubiquitous and invariant expression. We
      conclude that the evidence is against any such simple categorization and that a
      more pragmatic, less dogmatic, approach to the selection and implementation of
      reference genes is required, which takes into account the particular issues that
      pertain to human brain tissue studies. This pragmatism extends to the issue of
      whether normalization should be to one or multiple reference genes. We end by
      making several recommendations toward a more flexible, transparent, and
      comprehensive approach to data presentation and analysis. We illustrate the
      review with examples from studies of schizophrenia and mood disorder.

PMID- 20673872
TI  - Epigenetic transmission of the impact of early stress across generations.
AB  - BACKGROUND: Traumatic experiences in early life are risk factors for the
      development of behavioral and emotional disorders. Such disorders can persist
      through adulthood and have often been reported to be transmitted across
      generations. METHODS: To investigate the transgenerational effect of early
      stress, mice were exposed to chronic and unpredictable maternal separation from
      postnatal day 1 to 14. RESULTS: We show that chronic and unpredictable maternal
      separation induces depressive-like behaviors and alters the behavioral response
      to aversive environments in the separated animals when adult. Most of the
      behavioral alterations are further expressed by the offspring of males subjected
      to maternal separation, despite the fact that these males are reared normally.
      Chronic and unpredictable maternal separation also alters the profile of DNA
      methylation in the promoter of several candidate genes in the germline of the
      separated males. Comparable changes in DNA methylation are also present in the
      brain of the offspring and are associated with altered gene expression.
      CONCLUSIONS: These findings highlight the negative impact of early stress on
      behavioral responses across generations and on the regulation of DNA methylation
      in the germline.

PMID- 20673873
TI  - Striatal and extrastriatal dopamine D2/D3 receptors in schizophrenia evaluated
      with [18F]fallypride positron emission tomography.
AB  - BACKGROUND: Alterations in dopamine D(2)/D(3) receptor binding have been reported
      in schizophrenia, and a meta-analysis of imaging studies has shown a modest
      elevation in striatum. Newer radioligands now allow the assessment of these
      receptors in extrastriatal regions. We used positron emission tomography with
      [(18)F]fallypride to evaluate D(2)/D(3) receptors in both striatal and
      extrastriatal regions in schizophrenia. METHODS: Twenty-one patients with
      schizophrenia and 22 matched healthy control subjects were scanned with an ECAT
      EXACT HR+ camera. Two-tissue compartment modeling and the reference tissue method
      gave binding potentials relative to nondisplaceable uptake, total plasma
      concentration, and free plasma concentration. These were compared between groups
      in five striatal and eight extrastriatal regions. Several regional volumes were
      lower in the patient group, and positron emission tomography data were corrected
      for partial volume effects. RESULTS: Binding potential values differed in three
      regions between groups. Values for binding potential relative to nondisplaceable
      uptake from two-tissue compartment modeling in patients and control subjects,
      respectively, were 28.7 +/- 6.8 and 25.3 +/- 4.3 in postcommissural caudate, 2.9
      +/- .7 and 2.6 +/- .4 in thalamus, and 1.8 +/- .5 and 2.1 +/- .7 in uncus. Loss
      of D(2)/D(3) receptors with age was found in striatal and extrastriatal regions
      and was greater in neocortex. CONCLUSIONS: Our study found selective alterations
      in D(2)/D(3) receptors in striatal and extrastriatal regions, consistent with
      some but not all previously published reports. As previously shown for the
      striatum, a more sensitive imaging approach for studying the role of dopamine in
      the pathophysiology of schizophrenia might be assessment of neurotransmitter
      levels rather than D(2)/D(3) receptor levels in extrastriatal regions.

PMID- 20673874
TI  - Use of eye movement monitoring to examine item and relational memory in
      schizophrenia.
AB  - BACKGROUND: Patients with schizophrenia may be impaired at remembering interitem
      and item-context relationships (relational memory), even when memory for items is
      intact. Here, we applied the novel approach of using eye movements to assess
      integrity of item and relational memory in schizophrenia. This method does not
      rely on introspection and may be more readily translated to animal models than
      traditional behavioral methods. METHODS: Sixteen healthy control subjects and 16
      patients were administered a scene memory task while eye movements were
      monitored. During testing, participants indicated whether the scenes were
      unchanged, contained a new item (item manipulation), had a change in item
      location (relational manipulation), or were new. It was predicted that memory
      would be disproportionately impaired when relational changes were made. RESULTS:
      Results confirmed that tasks were equally difficult and showed that patients were
      impaired identifying all scene types. These behavioral impairments were
      associated with more severe disorganization and negative symptoms. Eye movement
      results were more specific. Both groups looked disproportionately at critical
      regions of repeated versus novel scenes-an effect of scene repetition. However,
      in contrast with predictions, patients showed equivalent eye-movement-based
      memory impairment whether changes were relational or item-based. CONCLUSIONS:
      This is the first experiment to demonstrate that eye movements can be used to
      investigate item and relational memory in schizophrenia. The eye movement
      procedure was well tolerated and was more specific than behavioral measures with
      respect to memory impairment. Results suggest that eye movements may be of use in
      clinical trials and translational studies employing animal models.

PMID- 20673875
TI  - Psychiatric brain banking: three perspectives on current trends and future
      directions.
AB  - Postmortem human brain tissue is critical for advancing neurobiological studies
      of psychiatric illness, particularly for identifying brain-specific transcripts
      and isoforms. State-of-the-art methods and recommendations for maintaining
      psychiatric brain banks are discussed in three disparate collections, the
      National Institute of Mental Health Brain Tissue Collection, the Harvard Brain
      Tissue Resource Center, and the Mount Sinai School of Medicine Alzheimer's
      Disease and Schizophrenia Brain Bank. While the National Institute of Mental
      Health Brain Tissue Collection obtains donations from medical examiners and
      focuses on clinical diagnosis, toxicology, and building life span control
      cohorts, the Harvard Brain Tissue Resource Center is designed as a repository to
      collect large-volume, high-quality brain tissue from community-based donors
      across a nationwide network, placing emphasis on the accessibility of tissue and
      related data to research groups worldwide. The Mount Sinai School of Medicine
      Alzheimer's Disease and Schizophrenia Brain Bank has shown that prospective
      recruitment is a successful approach to tissue donation, placing particular
      emphasis on clinical diagnosis through antemortem contact with donors, as well as
      stereological tissue sampling methods for neuroanatomical studies and frozen
      tissue sampling approaches that enable multiple assessments (e.g., RNA, DNA,
      protein, enzyme activity, binding) of the same tissue block. Promising scientific
      approaches for elucidating the molecular and cellular pathways in brain that may
      contribute to schizophrenia are briefly discussed. Despite different perspectives
      from three established brain collections, there is consensus that varied
      networking strategies, rigorous tissue and clinical characterization, sample and
      data accessibility, and overall adaptability are integral to the success of
      psychiatric brain banking.

PMID- 20673876
TI  - Genome-wide association-, replication-, and neuroimaging study implicates HOMER1
      in the etiology of major depression.
AB  - BACKGROUND: Genome-wide association studies are a powerful tool for unravelling
      the genetic background of complex disorders such as major depression. METHODS: We
      conducted a genome-wide association study of 604 patients with major depression
      and 1364 population based control subjects. The top hundred findings were
      followed up in a replication sample of 409 patients and 541 control subjects.
      RESULTS: Two SNPs showed nominally significant association in both the genome
      wide association study and the replication samples: 1) rs9943849 (p(combined) =
      3.24E-6) located upstream of the carboxypeptidase M (CPM) gene and 2) rs7713917
      (p(combined) = 1.48E-6), located in a putative regulatory region of HOMER1.
      Further evidence for HOMER1 was obtained through gene-wide analysis while
      conditioning on the genotypes of rs7713917 (p(combined) = 4.12E-3). Homer1
      knockout mice display behavioral traits that are paradigmatic of depression, and
      transcriptional variants of Homer1 result in the dysregulation of cortical-limbic
      circuitry. This is consistent with the findings of our subsequent human imaging
      genetics study, which revealed that variation in single nucleotide polymorphism
      rs7713917 had a significant influence on prefrontal activity during executive
      cognition and anticipation of reward. CONCLUSION: Our findings, combined with
      evidence from preclinical and animal studies, suggest that HOMER1 plays a role in
      the etiology of major depression and that the genetic variation affects
      depression via the dysregulation of cognitive and motivational processes.

PMID- 20673877
TI  - Common variants in major histocompatibility complex region and TCF4 gene are
      significantly associated with schizophrenia in Han Chinese.
AB  - BACKGROUND: Schizophrenia is a complex major psychiatric disorder affecting ~1%
      of the world population. Recently, in a genome-wide association study and a
      follow-up in Caucasians, Stefansson et al. examined 7662 schizophrenic cases and
      29053 normal control subjects and reported seven common single nucleotide
      polymorphisms (SNPs) that were significantly (>10(-8)) associated with
      schizophrenia. METHODS: To investigate whether these risk SNPs were significantly
      associated in Han Chinese, we analyzed the seven SNPs in 2496 schizophrenia
      patients and 5184 normal control subjects. Because only three of the seven SNPs
      were polymorphic in Han Chinese, we genotyped two additional common SNPs from the
      same risk regions. RESULTS: Three SNPs, rs6932590 (p = .00096), rs3131296 (p =
      1.29 * 10(-6)), and rs3130375 (p = 1.76 * 10(-5)), mapping to the major
      histocompatibility complex region and one SNP rs2958182 (p = 3.64 * 10(-6))
      located in the TCF4 gene were significant in our sample set. A meta-analysis
      using published genome-wide association study results also supported our
      findings. CONCLUSIONS: Our results confirm that common risk factors in the major
      histocompatibility complex region and TCF4 gene are associated with schizophrenia
      in Han Chinese, but our results fail to show an association with SNP rs12807809
      in the NRGN gene.

PMID- 20673878
TI  - Nicotine withdrawal increases threat-induced anxiety but not fear:
      neuroadaptation in human addiction.
AB  - BACKGROUND: Stress response neuroadaptation has been repeatedly implicated in
      animal addiction models for many drugs, including nicotine. Programmatic
      laboratory research that examines the stress response of nicotine-deprived humans
      is necessary to confirm that stress neuroadaptations observed in animal models
      generalize to humans. METHODS: Two experiments tested the prediction that
      nicotine deprivation selectively increases startle response associated with
      anxiety during unpredictable threat but not fear during imminent, predictable
      threat. Dependent smokers (n = 117) were randomly assigned to 24-hour nicotine
      deprived or nondeprived groups and participated in one of two experiments wherein
      electric shock was administered either unpredictably (noncontingent shock;
      Experiment 1) or predictably (cue-contingent shock; Experiment 2). RESULTS:
      Nicotine deprivation increased overall startle response in Experiment 1, which
      involved unpredictable administration of shock. Age of first cigarette and years
      of daily smoking were significant moderators of this deprivation effect. Self
      reported withdrawal symptoms also predicted startle response during unpredictable
      shock. In contrast, nicotine deprivation did not alter overall or fear
      potentiated startle in Experiment 2, which involved predictable administration of
      shock. CONCLUSIONS: These results provide evidence that startle response during
      unpredictable threat may be a biomarker of stress neuroadaptations among smokers
      in nicotine withdrawal. Contrast of results across unpredictable versus
      predictable shock experiments provides preliminary evidence that these stress
      neuroadaptations manifest selectively as anxiety during unpredictable threat
      rather than in every stressful context. Individual differences in unpredictable
      threat startle response associated with withdrawal symptoms, age of first
      cigarette, and years daily smoking link this laboratory biomarker to clinically
      relevant indexes of addiction risk and relapse.

PMID- 20673879
TI  - Alpha phase locking predicts residual working memory performance in
      schizophrenia.
AB  - BACKGROUND: Working memory (WM) deficits are a core feature of schizophrenia.
      Recent electrophysiological evidence indicates that the brain systems for visual
      encoding are especially impaired. However, patients still achieve performance
      levels clearly above chance, which indicates the existence of residual mechanisms
      supporting WM encoding. The present study presents evidence that alpha phase
      locking of the electroencephalogram is a marker for such residual cognitive
      mechanisms. METHODS: Alpha phase locking during encoding into WM was compared
      between 17 patients with early-onset schizophrenia (EOS) and 17 healthy control
      subjects. Results of phase locking were correlated with accuracy. A median split
      based on alpha phase locking in patients was used to compare accuracy between
      control subjects and patients with high and low alpha phase locking. RESULTS:
      Alpha phase locking increased with WM memory load in both EOS and control
      subjects, although alpha phase locking was generally reduced in EOS. Furthermore,
      for EOS, a positive correlation between alpha phase locking and performance was
      obtained. Additionally, patients exhibiting high phase locking did not differ in
      performance from control subjects. CONCLUSIONS: These results provide the first
      evidence for a relationship between alpha phase locking and visual WM encoding.
      This neural mechanism seems to be preserved in some patients with schizophrenia
      and then allows them to attain normal performance levels.

PMID- 20673880
TI  - Objective cognitive performance associated with electroconvulsive therapy for
      depression: a systematic review and meta-analysis.
AB  - BACKGROUND: Electroconvulsive therapy (ECT) is the most acutely effective
      treatment for depression, but is limited by cognitive side effects. However,
      research on their persistence, severity, and pattern is inconsistent. We aimed to
      quantify ECT-associated cognitive changes, specify their pattern, and determine
      progression. METHODS: MEDLINE, EMBASE, PsycArticles, PsychINFO, PsychLIT, and
      reference lists were systematically searched through January 2009. We included
      all independent, within-subjects design studies of depressed patients receiving
      ECT where cognition was assessed using standardized tests. Main outcome was
      change in performance after ECT relative to pretreatment scores with respect to
      delay between finishing ECT and cognitive testing. We explored potential
      moderators' influence, e.g., electrode placement, stimulus waveform. RESULTS:
      Twenty-four cognitive variables (84 studies, 2981 patients) were meta-analyzed.
      No standardized retrograde amnesia tests were identified. Significant decreases
      in cognitive performance were observed 0 to 3 days after ECT in 72% of variables:
      effect sizes (ES) ranging from -1.10 (95% confidence interval [CI], -1.53 to 
      .67) to -.21 (95% CI, -.40 to .01). Four to 15 days post-ECT, all but one CI
      included zero or showed positive ES. No negative ES were observed after 15 days,
      with 57% of variables showing positive ES, ranging from .35 (95% CI, .07-.63) to
      .75 (95% CI, .43-1.08). Moderators did not influence cognitive outcomes after 3
      days post-ECT. CONCLUSIONS: Cognitive abnormalities associated with ECT are
      mainly limited to the first 3 days posttreatment. Pretreatment functioning levels
      are subsequently recovered. After 15 days, processing speed, working memory,
      anterograde memory, and some aspects of executive function improve beyond
      baseline levels.

PMID- 20673881
TI  - Exploring the favorable ion-exchange ability of phthalylated cellulose biopolymer
      using thermodynamic data.
AB  - A phthalylated ion-exchange biopolymer was obtained by adding cellulose to molten
      phthalic anhydride in a quasi solvent-free procedure. Through this route 2.99+/
      0.07 mmolg(-1) of pendant groups containing ester and carboxylic acid moieties
      were incorporated into the polymeric structure that was characterized by
      elemental analysis, solid-state carbon nuclear magnetic resonance (CP/MAS),
      infrared spectroscopy, X-ray diffraction, and thermogravimetry. The chemically
      modified polysaccharide is able to exchange cations from aqueous solution as
      demonstrated by batchwise methodology. The data were adjusted to a modified
      Langmuir equation to give 2.43+/-0.12 and 2.26+/-0.11 mmolg(-1) for divalent
      cobalt and nickel cations, respectively. The net thermal effects obtained from
      calorimetric titration measurements were also adjusted to a modified Langmuir
      equation, and the enthalpy of the interaction was calculated to give endothermic
      values of 2.11+/-0.28 and 2.50+/-0.31kJmol(-1) for these cations, respectively.
      The spontaneity of this ion-exchange process is reflected in negative Gibbs
      energy and with a contribution of positive entropic values. This set of
      thermodynamic data at the solid-liquid interface suggests a favorable ion
      exchange process for this anchored biopolymer for cation exchange from the
      environment.

PMID- 20673882
TI  - Iodine-catalyzed one-pot acetalation-esterification reaction for the preparation
      of orthogonally protected glycosides.
AB  - An iodine-catalyzed one-pot tandem acetalation-esterification reaction of thio-
      and O-glycosides has been developed providing a fast and mild route to
      orthogonally protected glycosides ready to be used as building blocks in
      glycosylation reactions.

PMID- 20673883
TI  - Polysaccharide purified from Polyporus umbellatus (Per) Fr induces the activation
      and maturation of murine bone-derived dendritic cells via toll-like receptor 4.
AB  - In this study, we report that a polysaccharide isolated from a Chinese medicinal
      herb, Zhu Ling (the sclerotium of Polyporus umbellatus (Per) Fr), induces
      phenotypic and functional maturation of murine bone-derived dendritic cells
      (BMDCs). Treatment of BMDCs with Polyporus polysaccharide (PPS) resulted in
      enhanced cell-surface expression of CD86, as well as enhanced production of both
      interleukin (IL)-12 p40 and IL-10 in a dose-dependent manner. In addition,
      treatment of BMDCs with PPS resulted in increased T cell-stimulatory capacity and
      decreased phagocytic ability. PPS-induced production of IL-12 p40 was inhibited
      by monoclonal antibodies to Toll-like receptor 4 (TLR4). Flow cytometric analysis
      showed that fluorescence-labeled PPS (f-PPS) bound specifically to BMDCs. This
      binding was blocked by both unlabeled PPS and anti-TLR4, but not by anti-TLR2 and
      anti-CR3 monoclonal antibodies. Taken together, our data show that PPS promotes
      the activation and maturation of murine BMDCs via TLR4.

PMID- 20673884
TI  - BDCA-2 signaling inhibits TLR-9-agonist-induced plasmacytoid dendritic cell
      activation and antigen presentation.
AB  - Plasmacytoid dendritic cells (PDCs) express Toll-like receptor (TLR) 9, which
      mediates recognition of microbial DNA during infection or self-DNA in autoimmune
      diseases. Triggering TLR-9 in PDC induces either maturation (lysosomal TLR-9
      triggering) or type I interferon (IFN-I) production (endosomal TLR-9 triggering).
      PDCs also express BDCA-2 (CD303), a C-type lectin receptor (CLR) unique to these
      cells. CLRs appear to function in innate immunity and microbial recognition, and
      may cooperate with TLRs to fine-tune inflammatory responses. It has been shown
      that anti-BDCA-2 monoclonal antibody is internalized by PDC for antigen
      presentation and inhibits TLR-9 induced IFN-I expression. Here we investigated
      the cross-talk between BDCA-2 and TLR-9-signaling during PDC maturation and
      antigen presentation. We found that BDCA-2-induced signaling in PDCs inhibits up
      regulation of CD86 and CD40 molecules in CpG-activated PDCs, but not in CD40L
      activated PDCs. Furthermore, triggering of BDCA-2 diminished the ability of CpG-
      and CD40L-stimulated PDCs to process and present antigen to antigen-specific
      autologous memory T cells. This study demonstrates that BDCA-2 represents an
      attractive target for clinical immunotherapy of IFN-I dependent autoimmune
      diseases influencing both, IFN-I production and antigen-specific T-cell
      stimulation by PDC.

PMID- 20673885
TI  - Early activation does not translate into effector differentiation of peripheral
      CD8T cells during the acute phase of Kawasaki disease.
AB  - Early diagnosis of acute Kawasaki disease (KD), lying in the spectrum between
      infectious and autoimmune diseases, can be difficult. To clarify the role of
      peripheral CD8T cells in KD, we examined their activation, proliferation,
      maturation, and effector function by four-color flow cytometry. Compared to
      healthy/febrile controls, acute KD patients showed striking increase in early
      activation marker CD69(+)CD8T cells and maturation subsets, but HLA-DR(+)CD8T
      cells representing late activation did not increase. Although Ki67(+)CD8T cells
      reflecting ongoing cell division increased in acute KD and febrile controls,
      absolute numbers of CD8T cells and maturation subsets decreased in acute KD
      versus healthy controls. Effector cells were lower in acute than in convalescent
      KD. Perforin(+)CD8T cells, denoting cytolytic activity, were lower in KD patients
      versus febrile controls. CD69(+)CD8T cells increase in acute KD but effector
      differentiation is absent. CD69(+)CD8T cells could be a marker to determine
      disease progression, treatment response, and convalescence in acute KD.

PMID- 20673886
TI  - Are executive skills primarily mediated by the prefrontal cortex in childhood?
      Examination of focal brain lesions in childhood.
AB  - INTRODUCTION: Based on the study of adults with brain insult, traditional
      localizationist views have argued that executive skills are primarily mediated by
      prefrontal cortex. It remains unclear whether a similar pattern of localization
      exists in childhood. METHODS: To investigate this hypothesis, we compared the
      performance of children, aged 7-16 years, with radiological evidence of brain
      pathology. The sample was divided according to lesion location as follows:
      frontal pathology (n=38), extra-frontal pathology (n=20), generalized pathology
      (n=21) and healthy controls (n=40). Using a multidimensional model of executive
      function described by Anderson (2002) and Anderson (1998; Anderson et al., 2001c,
      2001d), these groups were compared on a range of executive function domains
      including: attentional control, goal setting, cognitive flexibility, and
      information processing. Additional, non-executive measures were also
      administered. RESULTS: Contrary to adult lesion-based studies, there was little
      differentiation in executive processes between frontal and extra-frontal groups.
      CONCLUSIONS: These results provide support for contemporary models which propose
      a distributed, but integrated neural network for executive skills, suggesting
      that the integrity of the entire brain is necessary for adequate executive
      functions in childhood. Further, focal lesions to any brain region during
      development may render children vulnerable to a range of executive deficits that
      would not normally be expected following similar pathology in adulthood.

PMID- 20673887
TI  - Neurobehavioral effects of prenatal exposure to methylmercury and PCBs, and
      seafood intake: neonatal behavioral assessment scale results of Tohoku study of
      child development.
AB  - As factors affecting neonatal neurodevelopment, methylmercury, polychlorinated
      biphenyls (PCBs), and maternal seafood intake reflecting n-3 polyunsaturated
      fatty acids (PUFAs) are believed to have adverse or beneficial effects, but there
      are a few reports addressing such factors simultaneously. We carried out a birth
      cohort study to clarify the effects of these three factors on the Neonatal
      Behavioral Assessment Scale (NBAS), administered 3 days after birth. In a total
      of 498 mother-neonate pairs, the total mercury level (median, 1.96microg/g) in
      maternal hair at parturition and the summation operatorPCB level (45.5ng/g-lipid)
      in cord blood were analyzed, and maternal seafood intake was estimated using a
      semi-quantitative food frequency questionnaire. A negative relationship between
      the hair mercury level and the motor cluster of NBAS was observed, even after
      adjusting for PCBs, maternal seafood intake, and possible confounders such as
      maternal age, birth weight, and parity. The summation operatorPCB level was
      negatively correlated with the motor cluster, but this association was attenuated
      after adjusting for mercury and the confounders. There was seen to be a positive
      association between maternal seafood intake and the motor cluster when
      considering the effects of mercury and PCBs. In conclusion, our data suggest that
      prenatal exposure to methylmercury adversely affects neonatal neurobehavioral
      function; in contrast, maternal seafood intake appears to be beneficial. The
      neurobehavioral effect of prenatal exposure to PCBs remains unclear in our study.
      Further research is necessary to elucidate interactive effects of methylmercury,
      PCBs, and n-3 PUFAs, originating from fish, on child neurodevelopment.

PMID- 20673888
TI  - [Visits to the emergency department due to ecstasy (MDMA) and amphetamine
      derivative consumption: Epidemiological, clinical and evolutional profile].
AB  - OBJECTIVES: To describe clinical and epidemiologic characteristics of emergency
      department visits related with ecstasy usage, determine the rate of re-visits of
      the patients and their related factors. MATERIAL AND METHODS: The clinical
      histories of the patients coming to the Emergency Department for ecstasy-related
      problems were reviewed during 89 consecutive months in order to define the
      epidemiological and clinical profile. The computerized system of admission was
      used to study re-visits to the emergency department, reviewing the clinical
      history of the re-visits to see if they were related with drug consumption.
      RESULTS: The study included 498 cases (71% male, mean age 26.5 years). The
      majority of the patients were attended on the weekend (66.6%) and at night (57%).
      Main complaints were anxiety or altered thoughts (32.8%), agitation (17.2%),
      impaired awareness level (7.2%) and convulsions or abnormal movements (5.6%). A
      total of 81% of the patients had consumed other substances besides ecstasy,
      mainly ethanol (53%), cocaine (36%) and gammahydroxibutirate (liquid ecstasy,
      25%). Twenty six patients (5%) required admission to hospital (6 in the intensive
      care unit) and 4 died (0.8%). Fifteen percent of the patients were re-attended in
      the same ED for drug-related problems after a mean follow-up of 3 years, the new
      visit being more frequent during the first months. The need for an urgent
      psychiatric visit (OR: 6.3; 95% CI: 2.9-12.8) and hospital admission (OR: 3.5;
      95% CI: 1.5-8.4) during their first ED attendance were independently associated
      with a greater risk of re-attendance. CONCLUSIONS: Ecstasy consumption frequently
      leads to an ED visit, sometimes due to severe medical complications, and at least
      15% of patients will need urgent care again for drug-related problems within the
      next 3 years. This likelihood increases along with increased severity of the
      index episode (need of psychiatric consultation or hospital admission).

PMID- 20673889
TI  - Who identified endometriosis?
AB  - Although uterine adenomyoma and endometriosis were described around the turn of
      the 19th century, the history of the identification of endometriosis has remained
      controversial and continues to confuse recent literature affecting the management
      of the disease. Using histologic parameters of endometrial structure and
      activity, the first scientist to identify the condition, under the name
      "adenomyoma," was Thomas Cullen. John Sampson was the first to identify the
      pathogenesis of the condition.

PMID- 20673890
TI  - High levels of mineralocorticoids in preovulatory follicular fluid could
      contribute to oocyte development.
AB  - OBJECTIVE: To identify aldosterone and precursors in ovarian follicles and to
      relate levels of mineralocorticoids to previously described renin-angiotensin
      system follicular fluid content. DESIGN: Experimental. SETTING: Academic
      laboratory and affiliated large private practice. PATIENT(S): Women undergoing
      oocyte retrieval for in vitro fertilization (IVF). MAIN OUTCOME MEASURE(S): The
      concentrations of mineralocorticoids were measured in plasma and follicular
      fluid. Granulosa cell mRNA expression and oocyte receptor content were evaluated.
      RESULT(S): High concentrations of preovulatory aldosterone and corticosterone
      were measured in follicular fluid (419.5+/-122.2 and 218,383+/-124,143 pg/mL,
      respectively). Increased mineralocorticoid levels are found in follicular fluid
      compared with in plasma and in large follicles compared with in small. Plasma
      aldosterone levels increase before ovulation. Granulosa cell gene expression that
      promotes aldosterone production and accumulation of corticosterone is increased
      in younger patients. Aldosterone receptors are localized to the surface of human
      oocytes. CONCLUSION(S): High levels of aldosterone and its precursor,
      corticosterone, were found in ovarian follicles. This combined with the presence
      of aldosterone receptors on oocytes suggests a possible role for aldosterone in
      oocyte development.

PMID- 20673891
TI  - Fertility in women after surgical treatment of nonepithelial ovarian tumors.
AB  - Conservative treatment is an acceptable option for women with nonepithelial
      ovarian tumors who wish to preserve fertility.

PMID- 20673893
TI  - Emergency response to the Haitian earthquake--as bad as it gets.

PMID- 20673892
TI  - Low-dose human chorionic gonadotropin versus estradiol/progesterone luteal phase
      support in gonadotropin-releasing hormone agonist-triggered assisted reproductive
      technique cycles: understanding a new approach.
AB  - It remains unclear how GnRH agonist (GnRHa) triggering affects the luteal phase,
      so we investigated the luteal phase after GnRHa triggering, supported with
      conventional E(2)/P with or without low-dose hCG. E(2)/P support, compared with
      low-dose hCG, induced a shorter luteal phase (11.2 +/- 1.1 vs. 15.0 +/- 1.6 days)
      and fewer subjective complaints (0 vs. 42%), whereas hCG caused more free fluid
      accumulation and enlarged ovaries than E(2)/P alone. Steroids and low-dose hCG
      differentially affected corpus luteum function, ovarian size, free fluid
      accumulation, and patient comfort.

PMID- 20673894
TI  - Preserved splenic function after angioembolisation of high grade injury.
AB  - BACKGROUND: After introducing splenic artery embolisation (SAE) in the
      institutional treatment protocol for splenic injury, we wanted to evaluate the
      effects of SAE on splenic function and assess the need for immunisation in SAE
      treated patients. METHODS: 15 SAE patients and 14 splenectomised (SPL) patients
      were included and 29 healthy blood donors volunteered as controls. Clinical
      examination, medical history, general blood counts, immunoglobulin
      quantifications and flowcytometric analysis of lymphocyte phenotypes were
      performed. Peripheral blood smears from all patients and controls were examined
      for Howell-Jolly (H-J) bodies. Abdominal doppler, gray scale and contrast
      enhanced ultrasound (CEUS) were performed on all the SAE patients. RESULTS:
      Leukocyte and platelet counts were elevated in both SAE and SPL individuals
      compared to controls. The proportion of memory B-lymphocytes did not differ
      significantly from controls in either group. In the SAE group total IgA, IgM and
      IgG levels as well as pneumococcal serotype specific IgG and IgM antibody levels
      did not differ from the control group. In the SPL group total IgA and IgG
      Pneumovax((r)) (PPV23) antibody levels were significantly increased, and 5 of 12
      pneumococcal serotype specific IgGs and IgMs were significantly elevated. H-J
      bodies were only detected in the SPL group. CEUS confirmed normal sized and well
      perfused spleens in all SAE patients. CONCLUSION: In our study non-operative
      management (NOM) of high grade splenic injuries including SAE, was followed by an
      increase in total leukocyte and platelet counts. Normal levels of immunoglobulins
      and memory B cells, absence of H-J bodies and preserved splenic size and
      intraparenchymal blood flow suggest that SAE has only minor impact on splenic
      function and that immunisation probably is unnecessary.

PMID- 20673895
TI  - Frequency of pressure ulcers in the paediatric population: a literature review
      and new empirical data.
AB  - BACKGROUND: Published pressure ulcer incidence and prevalence figures in the
      paediatric population vary widely. The frequency of pressure ulcers in the German
      paediatric population is unknown. Currently, a systematic synthesis of PU
      incidence and prevalence studies in paediatric settings is missing. OBJECTIVES:
      To determine the prevalence and incidence of pressure ulcers in the paediatric
      population and the anatomic sites that are most often affected; and whether
      pressure ulcer occurrence in German paediatric hospital samples is comparable to
      international figures. DESIGN: A systematic literature review and a secondary
      data analysis were conducted. METHODS: The MEDLINE und CINAHL databases were
      searched. Methodological quality of relevant studies was systematically
      evaluated, relevant data extracted and synthesised. Data from five German-wide
      pressure ulcer prevalence studies were analysed. RESULTS: In total, 19 studies
      were identified containing any information about pressure ulcer frequency in the
      paediatric population. Methodological quality of many studies was low. Taking
      only higher quality studies into account, pressure ulcer incidence was
      approximately 7% in the total paediatric population and 26% in the ICU setting.
      Prevalence estimates varied between 2% and 28%. Excluding grade 1 pressure
      ulcers, prevalence ranged from 1% to 5%. Especially in newborns and infants, the
      head was most often affected by pressure injuries. Many pressure ulcers were
      caused by medical devices. In Germany, pressure ulcer prevalence grade 1-4 in the
      general paediatric population was 2.3% (95% CI 1.4-3.6%). Excluding grade 1
      pressure ulcer, prevalence was 0.8% (95% CI 0.4-1.8%). CONCLUSIONS: Due to
      considerable methodological limitations and insufficient reporting there is a
      dearth of sound empirical evidence about pressure ulcer frequency in the
      paediatric population. Conducting and reporting of future studies must be
      improved. Pressure ulcer prevalence in German hospital samples was comparable to
      international figures. Newborns, infants, and small children are at higher risk
      to develop pressure ulcers at the occipital region as compared to other anatomic
      locations. The likelihood of developing sacral and heel pressure ulcers increases
      with increasing age and growth.

PMID- 20673896
TI  - Midnight census revisited: Reliability of patient day measurements in US hospital
      units.
AB  - BACKGROUND: Patient days are widely used in nurse staffing research and for
      nursing quality measurement. Nursing hours per patient day (NHPPD) and fall rates
      incorporate patient days in the denominator and are endorsed by the US National
      Quality Forum (NQF) as nursing sensitive consensus measures. Measurement error
      introduced by patient days would affect the accuracy of these nursing quality
      indicators. OBJECTIVES: The aim of this study was to assess the reliability of
      five patient day reporting methods accepted by the National Database of Nursing
      Quality Indicators (NDNQI). The specific aims were (1) to investigate the
      agreement of five patient day measurements with a defined quasi-gold standard,
      (2) to explore method bias by investigating the association of potential
      confounding variables with the differences between the routine measurements and
      the quasi-gold standard, and (3) to extrapolate the potential effect of bias of
      the patient day methods on nursing quality indicators. DESIGN: A multiple census
      study with a national convenience sample of hospital units in the US was
      conducted. SETTING: 260 out of 282 units (92%) from 54 hospitals sent bi-hourly
      patient census data for seven randomly selected days in September 2008. METHODS:
      The multiple census data comprised the quasi-gold standard and was compared with
      data routinely submitted to the database. Intraclass correlations were calculated
      for an agreement analysis. A Bayesian regression analysis was conducted to
      explore the impact of different data collection methods and the degree of short
      stay patients. RESULTS: Overall agreement between routine data and the quasi-gold
      standard was excellent (ICC [95% CI]: 0.967 [0.958-0.974]). A Bayesian regression
      analysis identified that two methods underestimated patient days and an
      interaction between the degrees of short stay patients and one of the data
      collection methods also affected patient day measurement by up to 7.6%.

PMID- 20673897
TI  - Stroke prevention care delivery: predictors of risk factor management outcomes.
AB  - BACKGROUND: Internationally, the development and implementation of stroke care
      guidelines have resulted in the evolution of stroke prevention outpatient clinics
      designed to accelerate patient access to treatment and behavioral risk reduction
      following transient ischemic attack or stroke. OBJECTIVES: To examine the extent
      to which selected demographic, social-psychological, physiological, and adherence
      characteristics predicted achievement of blood pressure and glucose targets in a
      group of patients referred to a Canadian stroke prevention clinic with confirmed
      transient ischemic attack (TIA) or stroke and hypertension and/or diabetes.
      PARTICIPANTS: A total of 313, English speaking, adult patients who were referred
      from family or emergency department physicians to a stroke prevention clinic
      provided demographic data and received social-psychological screening testing at
      intake. Of these, 93 participants who met criteria of confirmed TIA or stroke
      plus hypertension and/or diabetes were identified as the study group. Seventy
      seven of study group participants completed a 6-month follow-up. METHODS:
      Admission screening tests included the Modified and Mini-Mental State
      Examinations, Trail Making Test, Clock Drawing Test, a medication self-efficacy
      scale, the Lubben Social Network Scale and the Geriatric Depression Scale. Family
      physician follow-up was ascertained 4-8 weeks after intake. At approximately 6
      months after the initial screening measures, 77 study group participants
      completed additional measures of adherence, blood pressure and/or glycated
      hemoglobin. RESULTS: Transient ischemic attack was confirmed in 58% and stroke in
      42% of the study group. Mean age was 69 years (SD=11); 53% were male; 97% had
      hypertension; and 25% were diabetic; some had both. Twenty-three percent were not
      followed-up by family practitioners. At 6-month follow-up, 97% reported >=80%
      adherence to medication; only 57% met treatment targets. A logistic regression
      analysis identified three independent predictors of achieving blood pressure
      and/or glucose targets: self-efficacy expectations (OR, 1.61; 95% CI, 1.03-2.54;
      p=0.04), Mini-Mental State (OR, 1.28; 95% CI, 1.06-1.54; p=0.009); and self
      reported adherence (OR, 1.14; 95% CI, 1.01-1.29; p=0.03). CONCLUSIONS: Three
      simple screening measures identified patients at increased risk of not achieving
      clinical risk factor management targets.

PMID- 20673898
TI  - Transcutaneous very-high-resolution ultrasound to quantify arterial wall layers
      of muscular and elastic arteries: validation of a method.
AB  - BACKGROUND: High-resolution ultrasound (HRU) is used to measure carotid intima
      media thickness (IMT). We postulated that very-high-resolution ultrasound (VHRU,
      25-55MHz) provides more detailed information on arterial morphology. METHODS:
      Rabbit and pig arterial specimens and artificial elastin membranes were studied
      with HRU and VHRU, and compared to histology. Bilateral carotid, brachial,
      radial, ulnar, femoral, and tibial arteries were imaged in vivo in 15 humans to
      determine the precision of VHRU and in 53 teenagers to compare VHRU to HRU.
      RESULTS: The assessment of IMT, adventitia thickness (AT) and combined intima
      media-adventitia thickness (IMAT) in muscular arteries was accurate and precise
      by VHRU with the exception that the AT of the smallest arteries was not
      delineated with 25MHz. VHRU was accurate and precise for IMAT in small and for
      IMT in large elastic arteries and allowed to qualitatively assess elastin fibers
      of the media. HRU was accurate for IMT of large muscular and elastic arteries
      only. Intima thickness (IT) was grossly overestimated by both VHRU and HRU.
      CONCLUSION: Transcutaneous VHRU provides a noninvasive method of quantifying
      elastic and muscular arterial AT, IMT and IMAT in children and adults, but
      neither VHRU nor HRU is able to assess IT in non-diseased vessels.

PMID- 20673899
TI  - Analysis of saphenous vein graft lesion composition using near-infrared
      spectroscopy and intravascular ultrasonography with virtual histology.
AB  - OBJECTIVE: To examine the composition of saphenous vein graft (SVG) lesions using
      two novel modalities, near-infrared spectroscopy (NIRS) and intravascular
      ultrasonography with virtual histology (IVUS-VH). METHODS: We performed NIRS and
      IVUS-VH imaging of 23 SVGs in 21 patients undergoing clinically-indicated
      angiography. RESULTS: Mean patient and SVG age was 66+/-7 and 10+/-7 years,
      respectively. SVG lesion location was aorto-ostial in 8 (35%), body in 13 (57%)
      and distal anastomotic in 2 (9%). Compared to anastomotic lesions, body lesions
      had larger mean lumen area (6.4+/-1.8 mm2 vs. 4.2+/-6.4 mm2, P=0.02) but similar
      mean plaque burden (73+/-5% vs. 70+/-10%, P=0.66). A NIRS lipid core plaque was
      identified in 9 of 13 body lesions vs. 1 of 10 anastomotic lesions (69% vs. 10%,
      P=0.005). SVG body lesions had higher lipid core burden index (LCBI) compared to
      anastomotic lesions (184+/-76 vs. 49+/-54, P<0.001). By IVUS-VH, SVG lesions had
      high % necrotic core (28+/-10%) and % dense calcium (13+/-10%), without any
      significant difference between body and anastomotic sites. Older SVG age was
      associated with higher lesion and vessel LCBI (r=0.76 and r=0.64, respectively,
      P<0.001), but was not associated with IVUS-VH determined plaque composition.
      Higher HDL-cholesterol was associated with lower lesion LCBI (r=-0.43, P=0.04).
      CONCLUSIONS: NIRS-measured lipid core plaque in SVGs increases with increasing
      SVG age and is infrequent in anastomotic lesions. No association was found
      between IVUS-VH plaque composition measurements and SVG lesion location or age.

PMID- 20673900
TI  - Effects of mechanical loading patterns, bone graft, and proximity to periosteum
      on bone defect healing.
AB  - The goal of this study is to elucidate whether mechanobiological factors,
      including mechanical loading patterns, presence of bone graft, and proximity to
      the periosteum, correlate to de novo tissue generation and healing in critical
      sized long bone defects, which are enveloped by periosteum in situ and are
      bridged at 16 weeks, in sheep femora. Quantitative histomorphometric measures of
      defect cross sections show that, along the axis least able to resist bending
      loads (minor centroidal axis, CA), bone laid down in the first two weeks after
      surgery exhibits more mineralization albeit less total area compared to bone
      along the axis most able to resist bending loads (major CA). Similarly, areas of
      the cross section along the minor CA show a higher degree of perfusion albeit
      less total area of perfusion compared to bone along the major CA. Furthermore,
      proximity to the periosteal niche, in conjunction with the presence of bone graft
      and predominant loading patterns, relates significantly to the radial
      distribution of early bone apposition and perfusion of bone at 16 weeks after
      surgery (linear regression with R(2)>0.80). In the absence of graft, early bone
      density is relatively evenly distributed in the defect zone, as is the intensity
      of perfused tissue. As measured by a steeper average slope in intensity of
      fluorochrome (new bone) distribution between the periosteum and the IM nail, the
      presence of bone graft retards initial bone formation in the defect zone and is
      associated with less evenly distributed tissue perfusion (steeper slope)
      persisting 16 weeks after surgery. Finally, although the mean area of bone
      resorption is not significantly different within or between groups defined by the
      presence of graft and/or mechanical loading patterns in the defect zone, the mean
      area of infilling resorption spaces is significantly higher in areas of the
      defect zone least able to resist bending (minor CA) but is not significantly
      related to the presence of bone graft. To our knowledge, the use of the major and
      minor centroidal axes to relate prevailing mechanical loading patterns to area
      and density of early bone generation in bone defects has not been reported prior
      to this study and may provide a new means to assess structure-function
      relationships in de novo bone generation and healing of bone defects.

PMID- 20673901
TI  - Aliphatic carboxylic acids and alcohols as efficiency and elution strength
      enhancers in micellar liquid chromatography.
AB  - Micellar liquid chromatography (MLC) uses surfactant solutions as mobile phases
      with added organic additives to enhance both the elution strength and the
      chromatographic efficiency. Two aliphatic carboxylic acids (1-butanoic and 1
      pentanoic) were used as MLC additives and compared with the two corresponding
      alcohols (1-butanol, 1-pentanol) in terms of elution strength, efficiency and
      selectivity. A set of 11 phenol derivatives was used as probe compounds. All
      micellar mobile phases were prepared with sodium dodecylsulfate (SDS) with
      concentration ranging from 0.05 to 0.15M and the modifier content within 1.0 and
      5.0% (v/v). The elution strength of different mobile phases containing a constant
      amount of SDS and different amounts of modifiers; and mobile phases containing a
      constant amount of modifier and different SDS concentration were determined and
      discussed. The effect of the acid modifiers on efficiency was studied
      constructing van Deemter plots that showed no minimum within the 0.01-0.7mL/min
      flow rate range studied. Temperature effects were also studied constructing the
      classical van't Hoff plots. The slight curvature of the plots in the 25-70
      degrees C range may indicate some modification of the surfactant-bonded moiety
      layer on the stationary phase surface. Since no definitive advantage of the use
      of aliphatic acids were established compared to their alcohol counterpart, their
      terrible smell will probably preclude their use as MLC organic modifiers.

PMID- 20673902
TI  - The impact of sampling time on peak capacity and analysis speed in on-line
      comprehensive two-dimensional liquid chromatography.
AB  - Comprehensive two-dimensional liquid chromatography (2DLC) offers a number of
      practical advantages over optimized one-dimensional LC in peak capacity and thus
      in resolving power. The traditional "product rule" for overall peak capacity for
      a 2DLC system significantly overestimates peak capacity because it neglects under
      sampling of the first dimension separation. Here we expand on previous work by
      more closely examining the effects of the first dimension peak capacity and
      gradient time, and the second dimension cycle times on the overall peak capacity
      of the 2DLC system. We also examine the effects of re-equilibration time on under
      sampling as measured by the under-sampling factor and the influence of molecular
      type (peptide vs. small molecule) on peak capacity. We show that in fast 2D
      separations (less than 1h), the second dimension is more important than the first
      dimension in determining overall peak capacity and conclude that extreme measures
      to enhance the first dimension peak capacity are usually unwarranted. We also
      examine the influence of sample types (small molecules vs. peptides) on second
      dimension peak capacity and peak capacity production rates, and how the sample
      type influences optimum second dimension gradient and re-equilibration times.

PMID- 20673903
TI  - Development and validation of a nonaqueous capillary electrophoretic method for
      the enantiomeric purity determination of a synthetic intermediate of new 3,4
      dihydro-2,2-dimethyl-2H-1-benzopyrans using a single-isomer anionic cyclodextrin
      derivative and an ionic liquid.
AB  - The enantiomeric purity determination of a synthetic intermediate of new 3,4
      dihydro-2,2-dimethyl-2H-1-benzopyrans, i.e. 4-amino-2,2-dimethyl-6
      ethoxycarbonylamino-3,4-dihydro-2H-1-benzopyran, was successfully carried out
      using an anionic cyclodextrin (CD) derivative combined with a chiral ionic liquid
      (IL). In order to obtain high resolution and efficiency values, the addition of a
      chiral IL, i.e. ethylcholine bis(trifluoromethylsulfonyl)imide (EtChol NTf(2)),
      to the background electrolyte containing heptakis(2,3-di-O-methyl-6-O-sulfo)-beta
      CD (HDMS-beta-CD) was found to be essential. A simultaneous increase in
      separation selectivity and enantioresolution seems to indicate a synergistic
      effect of HDMS-beta-CD and EtChol NTf(2). The best enantioseparation of the key
      intermediate was achieved using a methanolic solution of 0.75M formic acid, 10mM
      ammonium formate, 1.5mM HDMS-beta-CD and 5mM EtChol NTf(2). Levamisole was
      selected as internal standard. The optimized conditions allowed the determination
      of 0.1% of each enantiomer in the presence of its stereoisomer using the method
      of standard additions. The NACE method was then fully validated with respect to
      selectivity, response function, trueness, precision, accuracy, linearity and
      limits of detection and quantification.

PMID- 20673904
TI  - Effects of the redox state of porous graphitic carbon on the retention of
      oligosaccharides.
AB  - Retention of hydrophilic compounds on porous graphitic carbon (PGC) is afforded
      by polar interactions with induced dipoles within this polarizable stationary
      phase. These interactions depend on the redox state of PGC, which can be
      influenced by application of an electrical field or by chemical means. We
      explored the impact of oxidizing and reducing agents on the retention of
      fluorescence labeled neutral oligosaccharides. Malto-oligosaccharides were
      employed as simple model system. Subsequently, the effects on the retention of
      glycans typical for immunoglobulin G (IgG) antibodies were investigated. Chemical
      oxidation of the PGC surface increased the retention of all analytes tested.
      Selectivities were significantly altered by the redox treatment, emphasizing the
      need for controlling the redox state of PGC to achieve reproducible conditions.
      Furthermore a column pre-conditioning protocol is presented, which allowed for
      reproducible chromatography of neutral IgG glycans.

PMID- 20673905
TI  - The solubilisation of a water insoluble functionalized silicone oil in an aqueous
      surfactant solution: a novel mechanism for the solubilisation process.
AB  - The solubilisation of the functionalized silicone oil aminoethyl aminopropyl
      methylpolysiloxane WR 1300 has been investigated in aqueous solutions of the
      surfactant pentaethoxy-iso-tridecanol (iC(13)E(5)). The silicone oil consists of
      a linear backbone with an average of 200 dimethylsiloxane units and 2-3
      functionalized side groups. In various applications the compound is considered a
      silicone oil. The surfactant iC(13)E(5) forms a L(alpha)-phase in water, and with
      decane a microemulsion can be obtained. The solubilisation experiments started
      with lamellar iC(13)E(5) phases. With proper amounts of WR 1300 transparent,
      optically isotropic but highly viscous single phases are formed. These phases
      cannot be considered true microemulsions with an oil core and a surrounding
      surfactant layer. Cryo-TEM micrographs show micelles with irregular shapes and
      about 25 nm diameter. Their size is independent of the oil/surfactant ratio. It
      can be explained on the basis of a model where the amino groups of the oil are
      all found at the surface of the micelles, limiting the radius of the aggregates
      to the largest length of the polydimethylsiloxane backbone between two such
      groups or between one end of the oil and one functionalized group. The micellar
      structures contain only a few siloxane molecules exposing their hydrophilic
      groups to the water. The functionalized silicone oil molecules can thus be
      considered as surfactant molecules with a few polar groups and a large
      hydrophobic chain from dimethyl siloxane.

PMID- 20673906
TI  - Degradability of poly(L-lysine) and poly(DL-aminoserinate) complexed with a
      polyanion under conditions modelling physico-chemical characteristics of body
      fluids.
AB  - Poly(L-lysine), (PLL), and poly(DL-amino serinate), (PSA), are respectively
      enzymatically and hydrolytically degradable polycations. This work was aimed at
      investigating their degradability when they are complexed with polyanions, namely
      poly(acrylic acid) and poly(L-lysine citramide), taken as simple models of DNA in
      polyplexes. Comparison was made with degradation characteristics of the same
      polycations in solution in the absence of polyanion on the basis of size
      exclusion chromatography and capillary zone electrophoresis. Complexed PLL
      remained enzymatically degradable by trypsin, an endopeptidase, but was no longer
      degradable by aminopeptidase, an exopeptidase. Trypsin yielded a mixture of
      trilysin and tetralysin. Complexed PSA remained hydrolytically degradable in
      aqueous media. The hydrolysis of PSA led to DL-serine. However, traces of anionic
      species were also detected that were identified as residues of constituting
      repeating units issued from the N-benzyloxycarbonyl polyaminoserinate precursor
      (PSAZ).

PMID- 20673907
TI  - A facile approach to the fabrication of graphene/polystyrene nanocomposite by in
      situ microemulsion polymerization.
AB  - This paper reports a large scale production route for polystyrene (PS)
      nanoparticle-functionalized graphene sheets using water based in situ
      microemulsion polymerization. The higher surface area of the graphene basal plane
      and the better proximity of the reactant species in in situ microemulsion
      polymerization were used to functionalize the graphene sheets using PS
      nanoparticles. The thermal properties of the PS were improved with the
      incorporation of graphene in the composite. The modified graphene exhibited good
      compatibility and interactions with the host PS matrix to form conducting PS
      films.

PMID- 20673908
TI  - A novel method to control inner and outer haze of an anti-glare film by surface
      modification of light-scattering particles.
AB  - Anti-glare films with various inner haze and outer haze were fabricated by a
      novel and simple method to modify the surface of the light-scattering particles
      via an acid or base treatment. The mechanism of formation of the inner and outer
      haze was investigated by the morphology of the AG coating layer. When the solvent
      evaporated, the treated light-scattering particles easily aggregated in the AG
      coating layer, increasing the outer haze and decreasing the inner haze. XPS
      analysis revealed that this result may have resulted from partial removal of the
      stabilizers on the light-scattering particles by the acid or base treatment. In
      this study, we demonstrated that the ratio of outer haze to inner haze varied
      from 0.32 to 3.14 with the same relative composition of particle, resin, and
      solvent in the AG coating; this ratio could be controlled by adjusting the
      proportion of untreated particles to treated particles.

PMID- 20673909
TI  - Technique for characterization of the wettability properties of gas diffusion
      media for proton exchange membrane fuel cells.
AB  - In this paper, a measurement technique based on the capillary penetration method
      is presented for use in estimating the wettability properties of gas diffusion
      media (GDM), a component for proton exchange membrane fuel cells (PEMFCs). The
      present method solves several critical issues, including the formation of an
      external meniscus and the evaporation of imbibed solvent, both of which greatly
      affect the apparent rate of solvent imbibition. Solvent evaporation is prevented
      by inserting a GDM sample between two thin stainless steel plates to form a tri
      layer structure having non-porous evaporation covers on each side of the porous
      GDM sample. The presence of stainless steel plates in contact with the GDM sample
      was demonstrated to have a negligible impact on the evaluation of the Washburn
      material constant.

PMID- 20673910
TI  - Aggregation and adsorption behavior of cetylpyridinium chloride in aqueous sodium
      salicylate and sodium benzoate solutions.
AB  - The critical micelle concentration (cmc) values of cetylpyridinium chloride (CPC)
      were determined in the presence of salicylate and benzoate ions in the less
      explored concentration region where viscosity is Newtonian. The cmc of CPC
      decreased from 9 x 10(-4) to 7 x 10(-7) and 3 x 10(-6) mol kg(-1) by adding about
      0.3 mol kg(-1) of salicylate and benzoate, respectively. The ortho hydroxyl group
      in salicylate thus has a remarkable influence on the micellization of CPC and the
      extent of this favorable effect is found to be about 3.5 kJ mol(-1). The Corrin
      Harkins equation was modified to explain the variation of cmc with electrolyte
      concentration in the presence of mixed counterions. The slope of the equation
      does not provide the value of the total counterion binding constant (beta), but
      gives us information about the lower limit to the value of beta, which is found
      to be 0.66. Addition of salicylate and benzoate increases the counterion binding
      to CPC micelles compared to that in the presence of chloride alone. An adsorption
      isotherm was derived to estimate the surface excess of CPC in the presence of
      mixed counterions.

PMID- 20673911
TI  - Non-word repetition in adolescents with specific language impairment and autism
      plus language impairments: a qualitative analysis.
AB  - Non-word repetition (NWR) was investigated in adolescents with typical
      development, Specific Language Impairment (SLI) and Autism Plus language
      Impairment (ALI) (n=17, 13, 16, and mean age 14;4, 15;4, 14;8 respectively). The
      study evaluated the hypothesis that poor NWR performance in both groups indicates
      an overlapping language phenotype (Kjelgaard & Tager-Flusberg, 2001). Performance
      was investigated both quantitatively, e.g. overall error rates, and
      qualitatively, e.g. effect of length on repetition, proportion of errors
      affecting phonological structure, and proportion of consonant substitutions
      involving manner changes. Findings were consistent with previous research
      (Whitehouse, Barry, & Bishop, 2008) demonstrating a greater effect of length in
      the SLI group than the ALI group, which may be due to greater short-term memory
      limitations. In addition, an automated count of phoneme errors identified poorer
      performance in the SLI group than the ALI group. These findings indicate
      differences in the language profiles of individuals with SLI and ALI, but do not
      rule out a partial overlap. Errors affecting phonological structure were
      relatively frequent, accounting for around 40% of phonemic errors, but less
      frequent than straight Consonant-for-Consonant or vowel-for-vowel substitutions.
      It is proposed that these two different types of errors may reflect separate
      contributory mechanisms. Around 50% of consonant substitutions in the clinical
      groups involved manner changes, suggesting poor auditory-perceptual encoding.
      From a clinical perspective algorithms which automatically count phoneme errors
      may enhance sensitivity of NWR as a diagnostic marker of language impairment.
      LEARNING OUTCOMES: Readers will be able to (1) describe and evaluate the
      hypothesis that there is a phenotypic overlap between SLI and Autism Spectrum
      Disorders (2) describe differences in the NWR performance of adolescents with SLI
      and ALI, and discuss whether these differences support or refute the phenotypic
      overlap hypothesis, and (3) understand how computational algorithms such as the
      Levenshtein Distance may be used to analyse NWR data.

PMID- 20673912
TI  - Mothers' autobiographical memory and book narratives with children with specific
      language impairment.
AB  - This study examined the role that mothers' scaffolding plays in the
      autobiographical memory (AM) and storybook narratives of children with specific
      language impairment (SLI). Seven 4-5-year-old children and their mothers co
      constructed narratives in both contexts. We also compared children's narratives
      with mothers to their narratives with an experimenter. Narratives were assessed
      in terms of narrative style (i.e., elaborativeness) and topic control. Mothers'
      elaborative and repetitive questions during AM and book narratives were related
      to children's elaborations, whereas mothers' elaborative and repetitive
      statements were not. Mothers produced more topic-controlling utterances than
      children in both contexts; however, both mothers and children provided
      proportionally more information in the book context. Additionally, children were
      more elaborative with mothers compared to an experimenter. LEARNING OUTCOMES:
      Readers will be able to: (1) understand the importance of mother-child narratives
      for both typical and clinical populations; (2) understand how mother-child
      autobiographical memory and storybook narratives may differ between typical and
      clinical populations; and (3) consider the implications for designing narrative
      intervention studies for language impaired children.

PMID- 20673913
TI  - Toward discerning the mechanisms of atrial fibrillation from surface
      electrocardiogram and spectral analysis.
AB  - Atrial fibrillation (AF) is the main cause of stroke and the most common
      sustained arrhythmia, afflicting about 2.3 million Americans. Clinical treatment
      and management of AF would benefit from a noninvasive and global assessment of
      the arrhythmia; however, that avenue seems currently limited in part by our poor
      understanding of arrhythmia itself. Experimental studies of AF in the isolated
      sheep heart demonstrated that high-frequency sources in the posterior wall of the
      left atrium drive the fibrillatory activity throughout both atria. Motivated by
      those results and by a growing body of work investigating how measurements of the
      cycle length of activity in patients during AF can contribute to its treatment,
      we focused our analysis on the dispersion of dominant frequency (DF) of the
      activity during AF in humans. Using electroanatomic mapping and Fourier methods,
      we generated 3-dimensional intracardiac DF maps of the atria in patients before
      AF ablation procedures and identified relatively small high-DF (HDF) sites. In
      patients with paroxysmal AF, the HDF sites are often localized to the posterior
      left atrium near the ostia of the pulmonary veins. In contrast, patients with
      permanent AF demonstrate HDF sites that are more often localized to the atria
      than the posterior left atrium-pulmonary vein junction. In our study, ablation at
      HDF sites resulted in significant slowing of the arrhythmia and termination of
      sustained AF in 87% of patients with paroxysmal AF. Furthermore, we found that
      abolishing, by ablation, preexisting left atrium to right atrium DF gradients
      predicted long-term freedom of AF in both paroxysmal and persistent AF patients.
      Overall, the analysis of intracardiac electrical recordings in the frequency
      domain has greatly enhanced our understanding of its underlying mechanisms and
      may contribute to monitoring drug effects and guide ablation procedures aiming at
      its termination. On the other hand, current body surface mapping methods have
      also suggested better correlations between surface AF frequency and intracardiac
      local DFs as compared with spatiotemporal activation patterns. Therefore, further
      study of the correlation of spectral observables obtained from the atria and from
      the surface electrocardiogram during AF seems to have the potential to advance
      our ability to diagnose and discern mechanisms of AF noninvasively.

PMID- 20673914
TI  - The development of children's early memory skills.
AB  - A multitask battery tapping nonverbal memory and language skills was used to
      assess 60 children at 18, 24, and 30 months of age. Analyses focused on the
      degree to which language, working memory, and deliberate memory skills were
      linked concurrently to children's Elicited Imitation task performance and whether
      the patterns of association varied across the different ages. Language ability
      emerged as a predictor of immediate Elicited Imitation performance by 24 months
      of age and predicted delayed performance at each age. In addition to the
      contributions of language, children's abilities to search for and retrieve toys
      in the deliberate memory task were associated with their immediate Elicited
      Imitation performance at each age. In addition to language, working memory was
      positively associated with aspects of both immediate and delayed performance at
      all ages. The extent to which it was possible to replicate and extend previous
      cross-sectional work in this longitudinal study is discussed.

PMID- 20673915
TI  - Physical activity, fitness, weight status, and cognitive performance in
      adolescents.
AB  - OBJECTIVE: To examine the association of participation in physical sports
      activity during leisure time, sedentary behaviors, cardiorespiratory and muscular
      fitness, and weight status with cognitive performance in Spanish adolescents.
      STUDY DESIGN: This cross-sectional study comprised a total of 1820 adolescents
      (958 female) aged 13.0 to 18.5 years. Cognitive performance (verbal, numeric and
      reasoning abilities, and an overall score) was measured with the "SRA-Test of
      Educational Ability." Participation in physical sports activity during leisure
      time (yes/no) and time devoted to study, television viewing, and playing video
      games were self-reported and categorized as <= 3 hours/day and >3 hours/day. We
      assessed cardiorespiratory and muscular fitness with field-based tests.
      Adolescents were classified as underweight, normal weight, overweight, and obese.
      RESULTS: Participation in physical sports activities during leisure time was
      associated with better cognitive performance study variables (all P < .001),
      independent of potential confounders including cardiorespiratory fitness and body
      mass index. We did not observe an association of time devoted to study,
      television viewing, or playing video-games with cognitive performance. Likewise,
      cognitive performance was similar across cardiorespiratory and muscular fitness
      levels and body weight categories. CONCLUSION: Participation in physical sports
      activity during leisure time may positively influence cognitive performance in
      adolescents.

PMID- 20673916
TI  - Evidence for subtle verbal fluency deficits in occasional stimulant users: quick
      to play loose with verbal rules.
AB  - Psychostimulants like cocaine and amphetamine are commonly abused by young adults
      who often state that they take these drugs to increase social or cognitive
      performance. The current study tested the hypothesis that individuals at early
      stages of occasional stimulant use show subtle executive dysfunctions such as
      verbal fluency deficits. 155 young (age 18-25), non-dependent occasional users of
      stimulants and 49 stimulant naive comparison subjects performed the Delis-Kaplan
      Verbal Fluency test. Correlation and median split analyses were conducted to
      account for stimulant history and co-drug use. Compared to stimulant naive
      subjects, occasional stimulant users generated significantly more responses on an
      over-learned verbal fluency task (Category Fluency), but at the expense of
      increased error rates (Set Loss and Repetition Errors). These performance
      differences were not related to lifetime uses of stimulants or marijuana. Taken
      together, these results support the hypothesis that individuals who are using
      stimulants occasionally exhibit subtle executive dysfunctions when required to
      generate verbal sets under time pressure. In particular, occasional stimulant
      users apply quickly but inaccurately verbal rules, which may represent a mix of
      diminished cognitive flexibility along with increased rigidity and impulsivity.
      This specific executive dysfunction may help to identify individuals at risk for
      stimulant use or dependence.

PMID- 20673917
TI  - Stress hormones during flooding therapy and their relationship to therapy outcome
      in patients with panic disorder and agoraphobia.
AB  - In spite of excessive fear during a panic attack, studies have found no or little
      evidence for an activation of cortisol during natural panic attacks. Whether this
      phenomenon is related to psychopathology or outcome of psychotherapy is unknown.
      In this study, 10 patients with panic disorder and agoraphobia were treated with
      cognitive behavioural therapy including 3 in-vivo exposures (flooding) to
      individual phobic situations. Before, during and after exposure, the level of
      subjective fear was assessed and blood was collected simultaneously. Cortisol and
      ACTH were analysed from plasma. Ten matched healthy control subjects went through
      the same procedure. Fear and stress hormones during exposure were compared in
      patients and controls as well as related to therapy outcome at the end of therapy
      and 2 follow-ups in patients. Results showed that the concentrations of cortisol
      and ACTH did not significantly increase during exposure. Patients' cortisol
      concentrations were higher than those of controls at baseline and during
      exposure, while ACTH concentrations were comparable before and during exposure,
      and even lower than those of controls at recovery. Cortisol concentrations were
      moderately but consistently correlated to therapy outcome, i.e. patients with
      least cortisol release during exposure profited least from therapy. The study
      showed that a lack of stimulation of the HPA system at repeated confrontation
      with the phobic situation was related to therapeutic outcome. Mechanisms of
      action via the influence of cortisol on extinction learning or the inhibition of
      central excitatory neurotransmission are conceivable.

PMID- 20673919
TI  - Characteristics and correlates of sensory function in chronic inflammatory
      demyelinating polyneuropathy.
AB  - BACKGROUND: Sensory assessments are included in clinical and research practice in
      chronic inflammatory demyelinating polyneuropathy (CIDP). However, their
      characteristics and relevance in relation to motor involvement and function have
      rarely been studied. OBJECTIVES: To investigate the characteristics and
      correlates of sensory function in CIDP. METHODS: We evaluated the sensory
      clinical and electrophysiological features in 31 clinically-stabilized,
      prospectively recruited, CIDP patients and analyzed their relation with motor
      strength and function as well as with electrophysiology. RESULTS: Sensory
      function primarily affected large fibres and was predominant in the lower limbs.
      Sensory Sum Scores (SSS) correlated with Medical Research Council (MRC) motor
      scores, Overall Neuropathy Limitation Scores (ONLS) and presence of positive
      sensory symptoms, in upper and lower limbs. Rydel-Seiffer vibration scores
      correlated with MRC and ONLS scores, in the lower limbs only. Correlations of SSS
      with sensory nerve action potential (SNAP) amplitudes and summated compound
      muscle action potential (CMAP) amplitudes, were present in the lower limbs but
      not in the upper limbs, whereas such correlations were ascertained in all
      extremities for Rydel-Seiffer scores. SNAPs correlated with ONLS scores
      exclusively in the legs. CONCLUSIONS: These results show that sensory involvement
      relates to motor function in CIDP, suggesting that the disease activity affects
      concurrently motor and sensory fibres in the disorder. The findings of this cross
      sectional analysis may otherwise suggest the practical reliability and usefulness
      of clinical sensory scores, particularly the SSS, in monitoring disease
      progression and effects of treatment in the disorder. Further longitudinal study
      is required to confirm this.

PMID- 20673918
TI  - Danaparoid sodium attenuates the effects of heat stress.
AB  - BACKGROUND: Heat stroke is a condition characterized by high body temperature
      that can lead to hemorrhage and necrosis in multiple organs. Anticoagulants, such
      as danaparoid sodium (DA), inhibit various types of inflammation; however, the
      anti-inflammatory mechanism of action is not well understood. Given that heat
      stroke is a severe inflammatory response disease, we hypothesized that DA could
      inhibit inflammation from heat stress and prevent acute heat stroke. MATERIALS
      AND METHODS: Male Wistar rats were given a bolus injection of saline or DA (50
      U/kg body weight) into the tail vein just prior to heat stress (42  degrees C for
      30 min). Markers of inflammation were then determined in serum and tissue
      samples. RESULTS: In rats pretreated with DA, induction of cytokines (interleukin
      [IL]-1beta, IL-6, and tumor necrosis factor [TNF]-alpha), nitric oxide (NO), and
      high mobility group box 1 (HMGB1) protein were reduced compared with saline
      treated rats. Histologic changes observed in lung, liver, and small intestine
      tissue samples of saline-treated rats were attenuated in DA-treated rats.
      Moreover, DA pretreatment improved survival in our rat model of heat stress
      induced acute inflammation. CONCLUSION: Collectively, our findings demonstrate
      that DA pretreatment may have value as a new therapeutic tool for heat stroke.

PMID- 20673920
TI  - LRRK2 Gly2385Arg polymorphism, cigarette smoking, and risk of sporadic
      Parkinson's disease: a case-control study in Japan.
AB  - Previous case-control studies in Japanese and ethnic Chinese populations reported
      that the LRRK2 Gly2385Arg variant is a risk factor for Parkinson's disease (PD).
      We aimed to validate the previous findings and investigate whether cigarette
      smoking influences the relationship between the Gly2385Arg variant and PD.
      Included were 229 cases within 6years of onset of sporadic PD. Controls were 358
      inpatients and outpatients without a neurodegenerative disease. The frequency of
      the heterozygous genotype was 13.1% of cases and 6.4% of controls: adjusted OR
      for the GA genotype was 2.06 (95% CI: 1.15-3.69). Compared with subjects with the
      GG genotype who had ever smoked, those with the GA genotype who had never smoked
      had a 5.8-fold increased risk of sporadic PD. The multiplicative interaction
      between the SNP and smoking was not statistically significant. With respect to
      the additive interaction, the estimated attributable proportion due to
      interaction (AP), but not relative excess risk due to interaction or the synergy
      index, was statistically significant (AP=0.50, 95% CI: 0.05-0.94), suggesting the
      presence of a biological interaction. The present study confirms that the LRRK2
      Gly2385Arg variant is a risk factor for sporadic PD. In addition, we provide new
      evidence for the biological interaction between the polymorphism and smoking with
      regard to the risk of sporadic PD.

PMID- 20673921
TI  - Re: Dipstick pseudohematuria: unnecessary consultation and evaluation. P. K. Rao,
      T. Gao, M. Pohl and J. S. Jones J Urol 2010; 183: 560-565.

PMID- 20673924
TI  - Re: Is suppression of hypothalamic-pituitary-adrenal axis significant during
      clinical treatment of phimosis? F. O. Pileggi, C. E. Martinelli, Jr., M. F. G. S.
      Tazima, J. C. Daneluzzi and Y. A. M. V. A. Vicente J Urol 2010; 183: 2327-2331.

PMID- 20673925
TI  - Developing erosion models for integrated coastal zone management: a case study of
      The New Caledonia west coast.
AB  - The tropical climate and human pressures (mining industry, forest fires) cause
      significant sediment inputs into the New Caledonia lagoon and are a major cause
      of degradation of the fringing reefs. The erosion process is spatially
      characterized on the west coast of New Caledonia to assess potential sediment
      inputs in the marine area. This paper describes the methodologies that are used
      to map soil sensitivity to erosion using remote sensing and a geographic
      information system tool. A cognitive approach, multi-criteria evaluation model
      and Universal Soil Loss Equation are implemented. This article compares the
      relevance of each model in order to spatialize and quantify potential erosion at
      catchment basin scale. These types of studies provide valuable results for
      focusing on areas subject to erosion and serve as a decision-making tool for the
      minimization of lagoon vulnerability to the natural and human dynamics on the
      level of the catchment basins.

PMID- 20673926
TI  - [Specialist palliative care home care support teams in Spain].

PMID- 20673927
TI  - [Donor lymphocyte infusions after allogeneic stem cell transplantation: single
      center clinical experience].
AB  - BACKGROUND AND OBJECTIVE: Donor lymphocyte infusions (DLI) have proven to be
      useful for the treatment of relapse after allogenic stem cell transplantation
      (SCT) and for the conversion of mixed chimerism (MC) into complete chimerism. The
      objective of the present study is to analyze the results of DLI used in both
      scenarios in a single centre. PATIENTS AND METHOD: Twenty five patients were
      retrospectively analyzed: DLI was used for relapse treatment in 18 cases and for
      conversion of mixed chimerism in 7. RESULTS: Six patients from the first group
      (35%) showed response in a median of 137 days (23-250). After a median follow-up
      of 12 months (7 months-8 years), 5 patients remained in complete remission.
      Additionally, one patient recieved prophylactic DLI with good results. Six of the
      7 patients (85%) who received DLI for MC showed response. After a median follow
      up of 7 years (6-8), 4 patients (57%) remained in remission. CONCLUSIONS: In our
      experience, DLI showed clinical benefit in the management of mixed chimerism,
      although it was less useful in the management of relapse. Novel strategies should
      be considered in high risk patients.

PMID- 20673928
TI  - Glucose metabolism after normalization of markers of iron overload by venesection
      in subjects with hereditary hemochromatosis.
AB  - Hereditary hemochromatosis (HH) is associated with abnormal glucose metabolism
      (AGM). We investigated the effect on glucose metabolism of normalization of the
      markers of iron overload by phlebotomy in subjects with HH. We prospectively
      studied 11 newly diagnosed subjects with HH and AGM using a standard 75-g oral
      glucose tolerance test. Basal quantitative insulin sensitivity check index
      (QUICKI) and stimulated oral glucose insulin sensitivity index (OGIS) insulin
      sensitivity was calculated from glucose and insulin data, whereas beta-cell
      function was assessed using C-peptide concentration after adjusting for ambient
      insulin sensitivity. After normalization of ferritin and transferrin saturations
      by venesection for 12 (range, 8-16) months, subjects were studied again using the
      same methods. From 11 subjects with AGM at the time that HH was diagnosed, 7 had
      impaired glucose tolerance (IGT) and 4 had type 2 diabetes mellitus (T2DM).
      Normalization of the iron stores (ferritin and transferrin) improved the glucose
      tolerance status of 4 patients with IGT (to normal glucose tolerance), whereas 2
      of those with IGT progressed to T2DM. In 5 patients, glucose tolerance status did
      not change (4 T2DM and 1 IGT). The area under the insulin and the C-peptide curve
      during the oral glucose tolerance test and the hepatic insulin extraction
      increased (P = .05), whereas no statistically significant changes occurred in
      insulin sensitivity. However, the disposition index, a measure of the ability of
      insulin release to compensate for insulin resistance, improved significantly (P =
      .02). Normalization of ferritin and transferrin saturation by venesection in
      subjects with HH and AGM led to improvements in some, but not all, measures of
      insulin secretion and action. Most patients with AGM had an improvement in
      glucose tolerance status, probably due to the augmented action of insulin in
      peripheral tissues.

PMID- 20673929
TI  - Ezetimibe decreases SREBP-1c expression in liver and reverses hepatic insulin
      resistance in mice fed a high-fat diet.
AB  - Ezetimibe inhibits intestinal cholesterol absorption, thereby reducing serum
      cholesterol. Recent studies suggest that ezetimibe affects liver steatosis and
      insulin resistance. We investigated the impact of ezetimibe on insulin
      sensitivity and glucose metabolism in C57BL/6 mice. We analyzed 4 mouse groups
      fed the following diets: normal chow (4% fat) for 12 weeks, normal chow for 10
      weeks followed by normal chow plus ezetimibe for 2 weeks, high-fat chow (32% fat)
      for 12 weeks, and high-fat chow for 10 weeks followed by high-fat chow plus
      ezetimibe for 2 weeks. In the normal chow + ezetimibe group, ezetimibe had no
      impact on body weight, fat mass, lipid metabolism, liver steatosis, glucose
      tolerance, or insulin sensitivity. In the high-fat chow + ezetimibe group,
      ezetimibe had no impact on body weight or fat mass but significantly decreased
      serum low-density lipoprotein cholesterol, triglyceride, and glutamate pyruvate
      transaminase levels; liver weight; hepatic triglyceride content; and hepatic
      cholesterol content and increased the hepatic total bile acid content. In
      association with increases in IRS-2 and Akt phosphorylation, ezetimibe
      ameliorated hepatic insulin resistance in the high-fat chow + ezetimibe group,
      but had no effect on insulin sensitivity in primary cultured hepatocytes. A DNA
      microarray and Taqman polymerase chain reaction revealed that ezetimibe up
      regulated hepatic SREBP2 and SHP expression and down-regulated hepatic SREBP-1c
      expression. SHP silencing mainly in the liver worsened insulin resistance, and
      ezetimibe protected against insulin resistance induced by down-regulation of SHP.
      Ezetimibe down-regulated SREBP-1c in the liver and reversed hepatic insulin
      resistance in mice fed a high-fat diet.

PMID- 20673930
TI  - Serum levels of angiopoietin-related growth factor are increased in metabolic
      syndrome.
AB  - Angiopoietin-related growth factor (AGF), a novel hepatokine, showed therapeutic
      implications in diabetic and obese animal models. Although the physiologic
      functions of human AGF have not yet been identified, serum levels of AGF
      displayed up-regulation in groups with diseases including preeclampsia and
      diabetes; and there was little association between genetic variability of AGF and
      metabolic syndrome-related phenotypes. We analyzed serum levels of AGF and other
      biochemical and anthropometric markers in 216 Korean persons--the numbers of
      healthy controls and those with metabolic syndrome were 138 and 78, respectively-
      to confirm research data from animal models. Women had higher AGF than men
      (265.01 vs 311.84 ng/mL, P = .003). This study showed that serum AGF levels were
      significantly higher in subjects with metabolic syndrome (325.89 ng/mL) than
      those in the healthy group (272.44 ng/mL) (P = .003). Among the components of
      metabolic syndrome, subjects with high waist circumference or decreased high
      density lipoprotein cholesterol had significantly increased serum AGF (271.92 vs
      313.68 ng/mL, P = .013; 271.01 vs 310.58 ng/mL, P = .023, respectively).
      According to multivariate regression analysis, metabolic syndrome itself and
      waist circumference could be used, in addition to sex and age, as predictors of
      serum AGF level. In conclusion, serum AGF levels were paradoxically increased in
      metabolic syndrome, in comparison with data from animal experiments and data on
      sex, age, and waist circumference. Metabolic syndrome can be a predictor of serum
      AGF level. Further studies are needed to explore the possibilities of
      compensatory up-regulation, or AGF resistance, to explain the physiologic roles
      of AGF in metabolic syndrome.

PMID- 20673931
TI  - Characterization of a xylose containing oligosaccharide, an inhibitor of
      multidrug resistance in Staphylococcus aureus, from Ipomoea pes-caprae.
AB  - Pescaprein XVIII (1), a type of bacterial efflux pump inhibitor, was obtained
      from the CHCl(3)-soluble resin glycosides of beach morning glory (Ipomoea pes
      caprae). The glycosidation sequence for pescaproside C, the glycosidic acid core
      of the lipophilic macrolactone 1 containing D-xylose and L-rhamnose, was
      characterized by means of several NMR techniques and FAB mass spectrometry.
      Recycling HPLC also yielded eight non-cytotoxic bacterial resistance modifiers,
      the two pescapreins XIX (2) and XX (3) as well as the known murucoidin VI (4),
      pecapreins II (6) and III (7), and stoloniferins III (5), IX (8) and X (9), all
      of which contain simonic acid B as their oligosaccharide core. Compounds 1-9 were
      tested for in vitro antibacterial and resistance-modifying activity against
      strains of Staphylococcus aureus possessing multidrug resistance efflux
      mechanisms. All of the pescapreins potentiated the action of norfloxacin against
      the NorA over-expressing strain by 4-fold (8 microg/mL from 32 microg/mL) at a
      concentration of 25 microg/mL.

PMID- 20673932
TI  - Toxicity of apolar and polar Lantana camara L. crude extracts in mice.
AB  - Lantana camara L, widely used in folk medicine, presents toxicity for farm
      animals. The acute poisoning effects of the apolar and polar L. camara L.
      extracts in mice were done. The percentage of death during 7 days after
      treatment, the acute signs of toxicity as well as the general activity observed
      in open field were assessed. The extracts were administered by i.p. route at 1.5,
      3.0 and 5.0 g/kg. Animals were evaluated during the first 2 h after the
      treatments to assess the acute signs of toxicity and daily observations were done
      for the presence of death. In the end of the experiment, at day 7, or immediately
      after death the animals had their organs removed, weighted and observed for
      macroscopic alterations. (1)H NMR and TLC analysis suggest the presence of
      triterpenoids in the apolar phase but not in the polar phase. Results showed also
      that both extracts produced similar percentage of death, mainly after 2 days of
      treatment; only the apolar extract presented a dose-dependent increased
      lethality. At necropsy, mice treated by both apolar and polar extracts were
      severely icteric, dehydrated and constipated, with hepatosis, showed congested
      heart and lung, and nephrosis; no skin lesions were shown. The main signs of
      toxicity revealed a decreased spontaneous general activity. In addition, it was
      observed a decreased duration of locomotion and animal rearing parallel to an
      increased immobility in the open field. The similarity of the signs related to
      the acute toxicity for both apolar and polar extracts suggested that the extracts
      have some of the active toxic principles in common. Data from open field behavior
      and spontaneous signs of toxicity suggest that the toxic principles have
      depressive properties on central nervous system.

PMID- 20673933
TI  - [Leeches of the upper aerodigestive tract].
AB  - INTRODUCTION: The leech is an aquatic worm living in fresh water, especially in
      tropical areas. It may be found exceptionally in the upper aerodigestive tract
      (UADT) after consumption of spring water or water from natural wells, after
      swimming in still waters (lakes and dams). The author's objective was to study
      epidemiological, clinical, therapeutic, and evolutive aspects of this
      infestation. PATIENT AND METHODS: This prospective 2-year study was carried out
      from January 1, 2007 to December 31, 2008. We included all patients consulting at
      the emergency unit presenting with leeches in the UADT. RESULTS: Twenty patients
      living in rural settings were included: 16 children, mostly boys (sex ratio 3:1).
      All cases were recorded during the summer season, with 14 cases due to
      consumption of fresh water and six due to swimming in still waters. The delay
      between infestation and onset of symptoms ranged from 2 to 15 days. Leeches were
      found in the oropharynx (six cases), the nasopharynx (five cases), the
      hypopharynx (six cases), and the glottis (three cases). An anemia syndrome was
      noted in four patients. All parasites were removed. All patients were given local
      antiseptics and analgesics. Patients with anemia were given iron supplementation.
      The outcome was favorable for all patients. DISCUSSION: UADT leeches are not
      uncommon in Morocco. The infestation is usually observed in the summer. Symptoms
      vary according to UADT localization. The diagnosis should be made rapidly to
      prevent complications. Whatever the localization, removing the parasite is
      difficult. In laryngeal localizations induction general anesthesia is
      recommended, without intubation. Evolution after treatment is rapidly favorable,
      with complete disappearance of symptoms.

PMID- 20673934
TI  - [Diagnosis contribution of biomarkers in Alzheimer disease: A case of
      frontotemporal dementia].
AB  - INTRODUCTION: Cerebrospinal fluid biomarkers are a fundamental contribution for
      the diagnosis of Alzheimer disease, in particular for young people. CASE REPORT:
      We report a case of Alzheimer disease of a 51-years old man whose clinical
      presentation corresponded to frontotemporal behavioural criteria. The clinical
      evaluation noticed some troubles in verbal memory. Only the CSF biomarkers
      confirmed the diagnosis. CONCLUSION: There are different phenotypes of presenile
      Alzheimer disease and among them we note frontotemporal dementia. It is very
      important to identify them to introduce a specific treatment.

PMID- 20673935
TI  - Plasmodium falciparum immunodetection in bone remains of members of the
      Renaissance Medici family (Florence, Italy, sixteenth century).
AB  - Medical accounts and ancient autopsy reports imply that tertian malarial fevers
      caused the death of four members of the Medici family of Florence: Eleonora of
      Toledo (1522-1562), Cardinal Giovanni (1543-1562), don Garzia (1547-1562) and
      Grand Duke Francesco I (1531-1587). All members of the Medici family hunted in
      the endemic malarial areas of Tuscany, such as the marshy areas surrounding their
      villas and along the swampy Maremma and were, therefore, highly exposed to the
      risk of being infected by Falciparum malaria. To determine if the original death
      certificates issued by the court physicians were correct, we carried out
      immunological investigations and then compared the biological results to the
      historical sources. Bone samples were examined for the presence of Plasmodium
      falciparum histidine-rich- protein-2 (PfHRP2) and P. falciparum lactate
      dehydrogenase (PfLDH) using two different qualitative double-antibody
      immunoassays. Our findings provide the first modern laboratory evidence of the
      presence of P. falciparum ancient proteins in the skeletal remains of four
      members of the Medici family. We confirm the clinical diagnosis of the court
      physicians, using modern methods. Finally, this study demonstrates that
      immunodetection can be successfully applied not only to mummified tissues but
      also to skeletal remains, thus opening new paths of investigation for large
      archaeological series.

PMID- 20673936
TI  - Reply to comment: Is PCR testing on blood samples useful or not in the diagnosis
      of Toxoplasma encephalitis?

PMID- 20673937
TI  - Microencapsulated citronella oil for mosquito repellent finishing of cotton
      textiles.
AB  - Microcapsules containing citronella essential oil were prepared by complex
      coacervation and applied to cotton textiles in order to study the repellent
      efficacy of the obtained fabrics. Citronella released from treated textiles was
      indirectly monitored by the extractable content of its main components. Repellent
      activity was assessed by exposure of a human hand and arm covered with the
      treated textiles to Aedes aegypti mosquitoes. Fabrics treated with
      microencapsulated citronella presented a higher and longer lasting protection
      from insects compared to fabrics sprayed with an ethanol solution of the
      essential oil, assuring a repellent effect higher than 90% for three weeks.
      Complex coacervation is a simple, low cost, scalable and reproducible method of
      obtaining encapsulated essential oils for textile application. Repellent textiles
      were achieved by padding cotton fabrics with microcapsules slurries using a
      conventional pad-dry method. This methodology requires no additional investment
      for textile finishing industries, which is a desirable factor in developing
      countries.

PMID- 20673938
TI  - Copro-molecular identification of infections with hookworm eggs in rural Lao PDR.
AB  - The prevalence of hookworm eggs in fecal samples, by modified cellophane thick
      smear technique, was found to be 30.0% (61/203 samples) in Lahanam Village,
      Savannakhet Province, Lao PDR. The hookworm eggs were morphologically
      heterogeneous, so that identification was confirmed by copro-PCR with specific
      primers for hookworms and Trichostrongylus spp.; 12 samples were positive for
      Necator americanus, 19 for Ancylostoma spp., with one mixed infection of both.
      Sequencing of the Ancylostoma spp. copro-PCR products found A. duodenale, and
      also the animal hookworms, A. caninum and A. ceylanicum. Moreover,
      Trichostrongylus spp.-specific copro-PCR revealed a significant rate of infection
      (43/203; 21.2%). Sequencing confirmed the zoonotic species, T. colubriformis.
      PCR/sequencing is useful for differentiating parasite species. The positives by
      the Kato-Katz method, and by the combined hookworm/Trichostrongylus specific-PCR,
      were comparable, although the agreement between the two methodologies was only
      50%.

PMID- 20673939
TI  - Left upper quadrant abdominal pain in malaria: suspect pathological splenic
      rupture first.

PMID- 20673940
TI  - Thickness-shear vibration of a quartz plate connected to piezoelectric plates and
      electric field sensing.
AB  - We study thickness-shear vibration of a quartz plate connected to two
      piezoelectric ceramic plates with initial deformations caused by a biasing
      electric field. The theory for small deformations superposed on finite biasing
      deformations in an electroelastic body is used. It is shown that the resonant
      frequencies of the incremental thickness-shear vibration of the quartz plate vary
      with the biasing electric field. The biasing electric field induced frequency
      shift depends linearly on the field. Therefore this effect may be used for
      electric field sensing. The dependence of the electric field induced frequency
      shift on various material and geometric parameters is examined. When the electric
      field is of the order of 100V/mm, the relative frequency shift is of the order of
      10(-5). The case when the piezoelectric plates are replaced by piezomagnetic
      plates is also investigated for magnetic field sensing, and similar results are
      obtained.

PMID- 20673941
TI  - Human papillomavirus E1 and E2 mediated DNA replication is not arrested by DNA
      damage signalling.
AB  - Integration of human papillomaviruses into that of the host promotes genomic
      instability and progression to cancer; factors that promote integration remain to
      be fully identified. DNA damage agents can promote double strand breaks during
      DNA replication providing substrates for integration and we investigated the
      ability of DNA damage to regulate HPV E1 and E2 mediated DNA replication. Results
      demonstrate that HPV E1 and E2 replication is not arrested following DNA damage,
      both in vivo and in vitro, while replication by SV40 Large T antigen is arrested
      and ATR is the candidate kinase for mediating the arrest. LTAg is a target for
      PIKK DNA damage signalling kinases, while E1 is not. We propose that the failure
      of E1 to be targeted by PIKKs allows HPV replication in the presence of DNA
      damaging agents. Such replication will result in double strand breaks in the
      viral genome ultimately promoting viral integration and cervical cancer.

PMID- 20673942
TI  - Characterization of H5N1 highly pathogenic avian influenza virus strains isolated
      from migratory waterfowl in Mongolia on the way back from the southern Asia to
      their northern territory.
AB  - H5N1 highly pathogenic avian influenza (HPAI) viruses were isolated from dead
      wild waterfowl at Khunt, Erkhel, Doityn Tsagaan, Doroo, and Ganga Lakes in
      Mongolia in July 2005, May 2006, May 2009, July 2009, and May 2010, respectively.
      The isolates in 2005 and 2006 were classified into genetic clade 2.2, and those
      in 2009 and 2010 into clade 2.3.2. A/whooper swan/Mongolia/6/2009 (H5N1)
      experimentally infected ducks and replicated systemically with higher mortality
      than that of the isolates in 2005 and 2006. Intensive surveillance of avian
      influenza in migratory waterfowl flying from their nesting lakes in Siberia to
      Mongolia in every autumn indicate that HPAI viruses have not perpetuated at their
      nesting lakes until 2009. The present results demonstrate that wild waterfowl
      were sporadically infected with H5N1 HPAI viruses prevailing in domestic poultry
      in the southern Asia and died in Mongolia on the way back to their northern
      territory in spring.

PMID- 20673943
TI  - Impacts of manipulated regime shifts in shallow lake model ecosystems on the fate
      of hydrophobic organic compounds.
AB  - Regime shifts in shallow lakes may significantly affect partitioning of sediment
      bound hydrophobic organic chemicals (HOCs) such as polychlorobiphenyls (PCB) and
      polycyclic aromatic hydrocarbons (PAH). In replicated experimental model
      ecosystems mimicking the alternative stable states 'macrophyte-dominated' and
      'suspended solid - phytoplankton dominated', we tested the effects of macrophytes
      and benthivorous fish presence on mass distribution and bioaccumulation of
      hexachlorobenzene, PCBs and PAHs. HOC mass distributions and lipid-normalized
      concentrations in sediment (Soxhlet- and 6-h Tenax-extractable), suspended
      solids, macrophytes, periphyton, algae, zooplankton, invertebrates and carp
      revealed that mobile, i.e. less hydrophobic or less aged HOCs were more
      susceptible to ecological changes than their sequestered native counterparts.
      Macrophytes were capable of depleting considerable percentages of the
      bioavailable, fast desorbing HOC fractions in the sediment upper (bioactive)
      layer, but did not have a significant diluting effect on lipid-normalized HOC
      concentrations in carp. Carp structured invertebrate communities through
      predation and stimulated partitioning of HOCs to other system compartments by
      resuspending the sediment. These results show that shifts in ecosystem structure
      have clear effects on fate, risks and natural attenuation of sediment-bound
      organic contaminants.

PMID- 20673944
TI  - Predominance of ammonia-oxidizing archaea on granular activated carbon used in a
      full-scale advanced drinking water treatment plant.
AB  - Ozonation followed by granular activated carbon (GAC) is one of the advanced
      drinking water treatments. During GAC treatment, ammonia can be oxidized by
      ammonia-oxidizing microorganisms associated with GAC. However, there is little
      information on the abundance and diversity of ammonia-oxidizing microorganisms on
      GAC. In this study, the nitrification activity of GAC and the settlement of
      ammonia-oxidizing archaea (AOA) and bacteria (AOB) in GAC were monitored at a new
      full-scale advanced drinking water treatment plant in Japan for 1 year after
      plant start-up. Prechlorination was implemented at the receiving well for the
      first 10 months of operation to treat ammonia in raw water. During this
      prechlorination period, levels of both AOA and AOB associated with GAC were below
      the quantification limit. After prechlorination was stopped, 10(5) copies g-dry(
      1) of AOA amoA genes were detected within 3 weeks and the quantities ultimately
      reached 10(6)-10(7) copies g-dry(-1), while levels of AOB amoA genes still
      remained below the quantification limit. This observation indicates that AOA can
      settle in GAC rapidly without prechlorination. The nitrification activity of GAC
      increased concurrently with the settlement of AOA after prechlorination was
      stopped. Estimation of in situ cell-specific ammonia-oxidation activity for AOA
      on the assumption that only AOA and AOB determined can contribute to
      nitrification suggests that AOA may account for most of the ammonia-oxidation.
      However, further validation on AOB contribution is required.

PMID- 20673945
TI  - Polymeric microspheres containing silver nanoparticles as a bactericidal agent
      for water disinfection.
AB  - A facile methodology has been developed by anchoring silver nanoparticles on to
      the macroporous methacrylic acid copolymer beads for disinfection of water in
      this study. Methacrylic acid copolymer beads are prepared by suspension
      polymerization technique. Silver nanoparticles formed on these copolymer beads by
      chemical reduction method are stable and are not washed away by water washing.
      Their stability is due to the interaction of nanoparticles with the carboxylic
      functional group on the copolymer beads. Copolymer beads containing silver
      nanoparticles are tested for their antibacterial activity against two gram
      positive and two gram negative bacteria. Antibacterial activity tested shows that
      they can be a potent biocidal material for water disinfection as they are highly
      effective against both gram positive and gram negative bacteria tested. The
      silver nanoparticles bound copolymer beads performed efficiently in bringing down
      the bacterial count to zero for all the strains tested except spore forming
      Bacillus subtilis which showed 99.9% reduction. There is no bacterial
      adsorption/adhesion on the copolymer beads containing silver nanoparticles
      proving them as effective water disinfectant.

PMID- 20673946
TI  - Effect of water composition, distance and season on the adenosine triphosphate
      concentration in unchlorinated drinking water in the Netherlands.
AB  - The objective of our study was to determine whether water composition, distance
      to the treatment plant and season significantly affect the adenosine triphosphate
      (ATP) concentration in distributed drinking water, in order to resolve the
      suitability of ATP as an indicator parameter for microbial regrowth. Results
      demonstrated that the ATP concentration in distributed water averaged between 0.8
      and 12.1 ng ATP L(-1) in the Netherlands. Treatment plants with elevated biofilm
      formation rates in treated water, showed significantly higher ATP concentrations
      in distributed drinking water and ATP content was significantly higher in the
      summer/autumn compared to the winter period at these plants. Furthermore,
      transport of drinking water in a large-sized distribution system resulted in
      significantly lower ATP concentrations in water from the distal than the proximal
      part of the distribution system. Finally, modifications in the treatment
      significantly affected ATP concentrations in the distributed drinking water.
      Overall, the results from our study demonstrate that ATP is a suitable indicator
      parameter to easily, rapidly and quantitatively determine the total microbial
      activity in distributed drinking water.

PMID- 20673947
TI  - Loading of fecal indicator bacteria in North Carolina tidal creek headwaters:
      hydrographic patterns and terrestrial runoff relationships.
AB  - In the New River Estuary (NRE) in eastern North Carolina (NC), fecal indicator
      bacteria (FIB) levels exceed water quality standards, leading to closure of
      estuarine waters for shellfishing and classification of parts of the estuary as
      "impaired" per the Clean Water Act section 303(d) list. As a means to investigate
      fecal contamination and loading of FIB to the NRE, a continuous automated sampler
      (ISCO) outfitted with flow modules and water quality probes was placed in four
      first-order tidal creek headwaters. Total storm discharge and bacterial load for
      Escherichia coli (EC) and Enterococcus spp. (ENT) were calculated using graphical
      volumetric flow calculations and interpolation of FIB measurements over each
      storm's duration for 10 storms. Mean total load of 10(9)-10(12) EC and ENT cells
      (MPN) occurred over the course of each storm. Total storm loading, averaged
      across all storms, was as much as 30 and 37 times greater than equivalent
      duration of baseflow loading for EC and ENT, respectively. Within the first 30%
      of creek storm volume for all storms and all creeks combined, a mean cumulative
      load of only 37% and 44% of the total EC and ENT cells, respectively, was
      discharged, indicating these creeks are not demonstrating a 'first flush'
      scenario for FIB. The median storm Event Mean Concentrations (EMCs) were 6.37 *
      10(2) and 2.03 * 10(2) MPN/100 mL, for EC and ENT, respectively, compared with
      median baseflow concentrations of 1.48 * 10(2) and 4.84 * 10(1) for EC and ENT,
      respectively, and were significantly different between base and storm flow
      events. FIB was correlated with TSS (weak), flow rate (strong), and different
      stages (base, rising, peak, and falling) of the hydrograph (strong).
      Pollutographs indicate large intra-storm variability of FIB, and the need for
      more intensive sampling throughout a storm in order to attain accurate FIB
      contaminant estimates. Instream sediment concentrations ranged from 5 to 478
      (MPN/g) and 13 to 776 (MPN/g) for EC and ENT, respectively, indicating sediment
      as a source, but a minor reservoir. This overall approach for calculating loading
      in headwater tidal creeks is detailed. Accurate loading characterization of FIB
      during storms and dry weather conditions, and understanding intra-storm FIB
      concentrations, is imperative for understanding patterns of water quality
      impairment, establishing management planning, and developing appropriate
      mitigation strategies.

PMID- 20673948
TI  - Monitoring of bacterial communities during low temperature thermal treatment of
      activated sludge combining DNA phylochip and respirometry techniques.
AB  - Sludge reduction is one of the major challenges in biological wastewater
      treatment. One approach is to increase the sludge degradation yield together with
      the biodegradation kinetics. Among the various sludge pretreatment strategies
      proposed, thermal pretreatment at around 65  degrees C was described as
      promising. The enhancement in the biodegradation activity due to the selection of
      thermophilic hydrolytic bacteria was proposed, but further experiments are needed
      to demonstrate the specific role of these bacteria. In this study, concentrated
      activated sludge grown at 20  degrees C was subjected to thermal treatment at 65 
      degrees C for different periods. The originality of the work relied on a
      polyphasic approach based on the correlation between kinetics (chemical oxygen
      demand, COD; mixed liquor suspended solids, MLSS), bacterial activity
      (respirometry) and bacterial community structure (phylochip monitoring) in order
      to characterize the mechanisms involved in the thermal reduction of sludge. The
      bacterial activity in the aeration basin decreased to a very low level when
      recycling sludge was treated at 65  degrees C from 13 to 60 h, but then, started
      to increase after 60 h. In parallel to these fluctuations in activity, a drastic
      shift occurred in the bacterial community structure with the selection of
      thermophilic bacteria (mainly related to genera Paenibacillus and Bacillus),
      which are known for their specific hydrolases.

PMID- 20673949
TI  - Treatment of dairy wastewater by inorganic coagulants: Parametric and disposal
      studies.
AB  - Present study reports treatment of simulated dairy wastewater (SDW) by inorganic
      coagulants such as poly aluminum chloride (PAC), ferrous sulphate (FeSO(4)) and
      potash alum (KAl(SO(4))(2).12H(2)O). Batch coagulation experiments were conducted
      to evaluate the influence of initial pH (pH(i): 5-10) and coagulant dosage (m:
      100-5000 mg/L) on chemical oxygen demand (COD) removal from SDW. Residual COD and
      system pH were observed as function of time. Optimum pH(i) (pH(i,op)) was found
      to be 8.0 for all the three coagulants. Optimum m (m(op)) was found to be 300,
      800 and 500 mg/L for PAC, FeSO(4) and KAl(SO(4))(2).12H(2)O, respectively, giving
      69.2, 66.5 and 63.8% COD removal efficiency in 30 min. Heating values of the
      sludge generated by the coagulants PAC, FeSO(4) and KAl(SO(4))(2).12H(2)O were
      found to be 20.7, 29.6 and 17.3 MJ/kg, respectively.

PMID- 20673950
TI  - Cryptosporidium and Giardia detection in water bodies of Galicia, Spain.
AB  - The objective of this study was to determine the mean concentration (per litre)
      of Cryptosporidium oocysts and Giardia cysts in recreational river areas (n =
      28), drinking water treatments plants (DWTPs; n = 52) and wastewater treatment
      plants (WWTPs; n = 50) in Galicia (NW Spain). Water samples from rivers and from
      the influent (50-100 l) and the treated effluent (100 l) of the water plants were
      filtered using Filta-Max filters (IDEXX Laboratories, Inc., Westbrook, ME, USA).
      A total of 232 samples were processed and the (oo)cysts were concentrated,
      clarified by IMS and then detected by IFAT. The viability was determined by
      applying fluorogenic vital dye (PI). In the recreational areas, infective forms
      of Cryptosporidium and Giardia were detected in 16 (57.1%; 1-60 oocysts per
      litre) and 17 (60.7%; 1-160 cysts per litre) samples, respectively. In the water
      flowing into the water treatment plants, oocysts were detected in 21 DWTPs
      (40.4%; 1-13 oocysts per litre) and cysts were observed in 22 DWTPs (42.3%; 1-7
      cysts per litre). In the effluents from the treatment plants, Cryptosporidium
      oocysts and Giardia cysts were identified in 17 DWTPs (32.7%; 1-4 oocysts per
      litre) and in 19 DWTPs (36.5%; 1-5 cysts per litre), respectively. The highest
      concentrations of (oo)cysts were found in the WWTPs; specifically, oocysts were
      detected in 29 (58.0%; 1-80 oocysts per litre) and cysts in 49 (98.0%; 2-14.400
      cysts per litre) WWTP effluents. Cryptosporidium and Giardia were detected in 32
      (64.0%; 1-120 oocysts per litre) and 48 (96.0%; 2-6.000 cysts per litre) WWTP
      effluents, respectively. The percentage viability of the (oo)cysts ranged between
      90.0% and 95.0%. In all samples analysed. Moreover, it was found that the
      effluents from coastal WWTPs were discharged directly into the sea, while inland
      WWTPs were discharged directly into rivers. The concentrations of both
      enteropathogens detected in effluents from WWTPs therefore represent a
      significant risk to human and animal health. These results demonstrate the wide
      distribution of Cryptosporidium and Giardia in the environment, the
      ineffectiveness of treatments in DWTPs and WWTPs in reducing/inactivating both
      protozoa and the need to monitor the presence, viability and infectivity of
      Cryptosporidium and Giardia in water bodies. In conclusion, the findings suggest
      the need for better monitoring of water quality and identification of sources of
      contamination.

PMID- 20673951
TI  - Hazard and risk assessment for indirect potable reuse schemes: An approach for
      use in developing Water Safety Plans.
AB  - This paper describes research undertaken to develop an approach for facilitating
      an initial hazard assessment and risk characterisation for a proposed indirect
      potable reuse scheme, as part of the water safety plan recommended by the World
      Health Organization. The process involved a description and evaluation of the
      catchment, which was the sewerage system supplying the sewage treatment works
      that would provide the effluent to supply the pilot scale indirect potable reuse
      water treatment plant. Hazards, sources and barriers throughout the proposed
      system were identified and evaluated. An initial assessment of the possible
      hazards, highlighted chemical hazards as predominating, and assessment of risks,
      using a heat map as output, categorised most hazards as medium or high risk.
      However, this outcome has been influenced by a precautionary approach which
      assigned a high likelihood to the occurrence of hazards where no data was
      available on their occurrence in the system. As more data becomes available, and
      the waster safety plan develops, it is anticipated that the risk heat map will
      become more specific. Additionally, high quality targets, to drinking water
      standards, have been set, although water from the potable reuse plant will be
      discharged to receiving waters where it will undergo natural attenuation prior to
      further treatment to potable standards before distribution. The assessment has
      demonstrated the usefulness of the approach where data is initially limited, in
      generating a heat map allowing for prioritisation of hazards to a practical
      level.

PMID- 20673952
TI  - Effect of air-flow rate and turning frequency on bio-drying of dewatered sludge.
AB  - Sludge bio-drying is an approach for biomass energy utilization, in which sludge
      is dried by means of the heat generated by aerobic degradation of its organic
      substances. The study aimed at investigating the interactive influence of air
      flow rate and turning frequency on water removal and biomass energy utilization.
      Results showed that a higher air-flow rate (0.0909m(3)h(-1)kg(-1)) led to lower
      temperature than did the lower one (0.0455m(3)h(-1)kg(-1)) by 17.0% and 13.7%
      under turning per two days and four days. With the higher air-flow rate and lower
      turning frequency, temperature cumulation was almost similar to that with the
      lower air-flow rate and higher turning frequency. The doubled air-flow rate
      improved the total water removal ratio by 2.86% (19.5gkg(-1) initial water) and
      11.5% (75.0gkg(-1) initial water) with turning per two days and four days
      respectively, indicating that there was no remarkable advantage for water removal
      with high air-flow rate, especially with high turning frequency. The heat used
      for evaporation was 60.6-72.6% of the total heat consumption (34,400-45,400kJ).
      The higher air-flow rate enhanced volatile solids (VS) degradation thus improving
      heat generation by 1.95% (800kJ) and 8.96% (3200kJ) with turning per two days and
      four days. With the higher air-flow rate, heat consumed by sensible heat of inlet
      air and heat utilization efficiency for evaporation was higher than the lower
      one. With the higher turning frequency, sensible heat of materials and heat
      consumed by turning was higher than lower one.

PMID- 20673953
TI  - beta-1,3-Glucan/antisense oligonucleotide complex stabilized with
      phosphorothioation and its gene suppression.
AB  - Most of antisense oligonucleotides (ASOs) subjected to current clinical
      evaluation belong to phosphorothioate (PS) analogues. Although PS has great
      advantage in DNase resistance, it can induce nonspecific side-effects. Thus it is
      important to investigate the influence of ASOs with different PS contents. In
      this paper, we prepared the complex consisting of schizophyllan (SPG) and ASOs
      attached a dA40 tail with different PS contents to the 3' end of the ODN, which
      is introduced to stabilize the complex with SPG. With increase of PS content in
      the dA40, its complexation ability with SPG was improved and the complex showed
      high thermal stability. The thermal stability of the fully phosphorothioated ASOs
      was obtained by only replacing 20% of the oxygen of the phosphodiester moiety.
      The ability of gene suppression between PS and phosphodiester for antisense
      sequences was almost the same, indicating that the antisense sequences need not
      to be PS backbone. These data may provide new insight for the interaction between
      beta-1,3-glucan and DNA and help to deliver therapeutic ODNs.

PMID- 20673954
TI  - Carbon and hydrogen isotope fractionation during anaerobic quinoline degradation.
AB  - Quinoline is a N-heterocyclic compound often found at tar oil contaminated field
      sites. To provide information whether stable isotope analysis can help to
      characterize the fate of quinoline within contaminated aquifers, carbon and
      hydrogen isotope fractionation of quinoline were investigated during
      biodegradation under sulfate-reducing conditions. No significant carbon isotope
      effect was observed, however, substantial hydrogen isotope fractionation was
      detected. Thus, hydrogen isotope fractionation may be used as an indicator for in
      situ biodegradation of quinoline. The bulk hydrogen isotope enrichment factor was
      epsilonH(bulk)=-33+/-120/00. During the biodegradation of quinoline the primary
      intermediate 2-hydroxyquinoline was detected indicating hydroxylation at the C2
      position. According to this reaction mechanism, the reactive position specific
      hydrogen enrichment factor (epsilonH(reactive position)) and apparent kinetic
      hydrogen isotope effect (AKIE(H)) were calculated and gave values of
      epsilonH(reactive position)=-205+/-750/00 and AKIE(H)=1.26+/-0.12, respectively.
      The missing carbon isotope effect may be explained by strong masking or an
      enzymatic direct side-on insertion of oxygen from the MoOH(H) group of the
      molybdenum center across the CH bond at the C2-position of quinoline with
      concomitant hydride transfer. The later assumption is supported by recent studies
      showing that initial step of hydroxylation of N-heteroaromatic compounds proceeds
      via a similar reaction mechanism.

PMID- 20673955
TI  - Evaluation of the aquatic toxicity of two veterinary sulfonamides using five test
      organisms.
AB  - The aquatic toxicity of sulfaquinoxaline (SQO) and sulfaguanidine (SGD) was
      evaluated on the following test organisms: Daphnia magna (reproduction test),
      Pseudokirchneriella subcapitata, Scenedesmus dimorphus, Synecococcus leopoliensis
      (algal growth inhibition test) and Lemna gibba (duckweed growth inhibition test).
      Furthermore, the additivity of the two compounds was measured on D. magna (acute
      immobilisation test) and P. subcapitata (algal growth inhibition test) using the
      isobologram method. Results show that SQO and SGD are more toxic to green algae
      and daphnids, respectively, than other veterinary sulfonamides (SAs) and that
      their mixtures have a less then additive interaction. Taking into account the
      highest concentrations detected so far in surface waters for SQO (0.112 MUg L(
      1)) and for SGD (0.145 MUg L(-1)) and the lowest NOECs obtained with the five
      test organisms, divided by an assessment factor of 10, the following PNECs and
      risk quotients (RQs) were calculated. SQO: PNEC 2 MUg L(-1); RQ 0.056. SGD: PNEC
      39.5 MUg L(-1); RQ 0.004. Consequently, at the concentrations actually detected
      in the aquatic environment, the two SAs alone should not harm the freshwater
      organisms. However, it seems advisable, for veterinary mass treatments, the use
      of other SAs that have a lesser impact on the aquatic environment. Furthermore,
      considering the high probability of having complex mixtures of different SAs
      residues in water, each individual contamination should be evaluated by applying
      to the SAs mixtures the conservative criteria of additivity.

PMID- 20673956
TI  - Occurrence of estrogens in sewage sludge and their fate during plant-scale
      anaerobic digestion.
AB  - Estrogens, which contribute greatly to the endocrine-disrupting activity in
      sewage, are partially sorbed onto particulate matter during sewage treatment. We
      thus investigated the occurrence of estrogens in different kinds of sludge and
      throughout a plant-scale anaerobic digestion process. The analytical method was
      first validated when sorption interaction between spiked estrogens and sludge
      could occur. Hence, the recovery ratio of estrone (E1), 17beta-estradiol (E2),
      estriol (E3) and 17alpha-ethinylestradiol (EE2) were determined when added to
      liquid sludge and mixed under various conditions. We show that minor non
      extractable residues were formed (5-10%), suggesting that the sorption
      interaction established with sludge did not limit estrogen extraction. Estrogen
      concentrations measured in collected samples varied with sludge type. Secondary
      sludge showed higher E1 contents than primary sludge: respectively, 43 and 8 ng
      g(-1) dry weight (dw). Two pathways of E1 production during secondary treatment
      are proposed to explain such a result. Higher estrogen concentrations were found
      in secondary sludge from a conventional plant (55 ng g(-1)dw) compared to those
      from an advanced plant (13 ng g(-1)dw). Based on estimated estrogen
      concentrations in sewage, we conclude that operating parameters play a role in
      the sorption of estrogens during secondary treatment. Also, the hydrophobic
      properties of the estrogens influenced the individual adsorption of each
      molecule. Thus, E3 showed the highest estimated concentrations in sewage but very
      low concentrations in sludge. Finally, plant-scale anaerobic digestion showed low
      efficiency (<40%) for removing estrogens and, regarding the final dewatering
      process, concentrations increased for E2 and EE2.

PMID- 20673957
TI  - Spatial distribution of metals in smelter-impacted soils of woody habitats:
      influence of landscape and soil properties, and risk for wildlife.
AB  - The spatial distribution of total and CaCl(2)-extracted Cd, Pb and Zn
      concentrations in smelter-impacted soils was investigated over a polluted site
      (40 km(2)) in Northern France. The study was conducted on 262 soils sampled in
      woody habitats. Total and extracted concentrations of trace metals (TMs) rose up
      to 2402 and 59.5 mg kg(-1) for Cd, 41 960 and 13.7 mg kg(-1) for Pb, 38 760 and
      143.0 mg kg(-1) for Zn, respectively. The spatial dependence of both total and
      extracted concentrations showed a high spatial auto-correlation and ordinary
      kriging was used to predict soil concentrations. Investigating which variables
      influenced metal concentrations and their spatial distribution, we found that
      total concentrations mostly depended on the distance from the smelter, the wind
      and the organic carbon, while extracted concentrations were mainly modulated by
      the pH. Conditionally to those variables, other soil properties and landscape
      characteristics influenced both total and extracted concentrations. We conclude
      that total and extracted TM concentrations are governed by different processes
      which act at various spatial ranges: total concentrations are mainly related to
      input and retention of metals (large scale) whereas extracted concentrations were
      mainly explained by factors controlling metal solubility in soils (local scale).
      Spatial distributions of total and extracted TMs differed over the area, which
      should be considered for risk assessment. Maps of risk based on the US EPA's Eco
      SSLs (for plants, invertebrates and vertebrates) were realized, showing that
      wildlife may be at risk but that the relevance of Eco-SSL values is questionable.

PMID- 20673958
TI  - Decrease in the abundance and viability of oceanic phytoplankton due to trace
      levels of complex mixtures of organic pollutants.
AB  - Long range atmospheric transport and deposition is a significant introduction
      pathway of organic pollutants to remote oceanic regions, leading to their
      subsequent accumulation in marine organisms. Persistent organic pollutants (POPs)
      bioconcentrate in planktonic food webs and these exert a biogeochemical control
      on the regional and global cycling of POPs. Therefore, an important issue is to
      determine whether the anthropogenic chemical perturbation of the biosphere
      introduced by the myriad of organic pollutants present in seawater influences
      phytoplankton abundance and productivity. The results reported here from five
      sets of experiments performed in the NE Atlantic Ocean show that there is a toxic
      effect induced by trace levels of complex mixtures of organic pollutants on
      phytoplankton oceanic communities. The levels of single pollutant, such as
      phenanthrene and pyrene, at which lethality of phytoplankton is observed are high
      in comparison to field levels. Complex mixtures of organic pollutants, however,
      have an important toxic effect on phytoplankton abundances, viability and
      concentrations of Chlorophyll a at pollutant concentrations 20-40 folds those
      found in the open ocean. The toxicity of these complex mixtures of organic
      pollutants exceeds by 10(3) times the toxicity expected for a single pollutant.
      Therefore, our results point out the need for a systematic investigation of the
      influence of complex mixtures of organic hydrophobic pollutants to oceanic
      phytoplankton communities, a perturbation not accounted for on previous
      assessments of anthropogenic pressures in the marine environment.

PMID- 20673959
TI  - Removal of oseltamivir (Tamiflu) and other selected pharmaceuticals from
      wastewater using a granular bioplastic formulation entrapping propagules of
      Phanerochaete chrysosporium.
AB  - The capacity of the ligninolytic fungus Phanerochaete chrysosporium to degrade a
      wide variety of environmentally persistent xenobiotics has been largely reported
      in the literature. Beside other factors, one barrier to a wider use of this
      bioremediation fungus is the availability of effective formulations that ensure
      easy preparation, handling and application. In this series of laboratory
      experiments, we evaluated the efficiency of a granular bioplastic formulation
      entrapping propagules of P. chrysosporium for removal of four selected
      pharmaceuticals from wastewater samples. Addition of inoculated granules to
      samples of the wastewater treatment plant of Bologna significantly increased the
      removal of the antiviral drug oseltamivir (Tamiflu), and the antibiotics,
      erythromycin, sulfamethoxazol, and ciprofloxacin. Similar effects were also
      observed in effluent water. Oseltamivir was the most persistent of the four
      active substances. After 30d of incubation, approximately two times more
      oseltamivir was removed in bioremediated wastewater than controls. The highest
      removal efficiency of the bioplastic formulation was observed with the antibiotic
      ciprofloxacin. Microbiological DNA-based analysis showed that the bioplastic
      matrix supported the growth of P. chrysosporium, thus facilitating its adaptation
      to unusual environment such as wastewater.

PMID- 20673960
TI  - Are groundwater nitrate concentrations reaching a turning point in some chalk
      aquifers?
AB  - In past decades, there has been much scientific effort dedicated to the
      development of models for simulation and prediction of nitrate concentrations in
      groundwaters, but producing truly predictive models remains a major challenge. A
      time-series model, based on long-term variations in nitrate fertiliser
      applications and average rainfall, was calibrated against measured concentrations
      from five boreholes in the River Frome catchment of Southern England for the
      period spanning from the mid-1970s to 2003. The model was then used to "blind"
      predict nitrate concentrations for the period 2003-2008. To our knowledge, this
      represents the first "blind" test of a model for predicting nitrate
      concentrations in aquifers. It was found that relatively simple time-series
      models could explain and predict a significant proportion of the variation in
      nitrate concentrations in these groundwater abstraction points (R(2)=0.6-0.9 and
      mean absolute prediction errors 4.2-8.0%). The study highlighted some important
      limitations and uncertainties in this, and other modelling approaches, in
      particular regarding long-term nitrate fertiliser application data. In three of
      the five groundwater abstraction points (Hooke, Empool and Eagle Lodge), once
      seasonal variations were accounted for, there was a recent change in the
      generally upward historical trend in nitrate concentrations. This may be an early
      indication of a response to levelling-off (and declining) fertiliser application
      rates since the 1980s. There was no clear indication of trend change at the
      Forston and Winterbourne Abbas sites nor in the trend of nitrate concentration in
      the River Frome itself from 1965 to 2008.

PMID- 20673961
TI  - A risk-benefit analysis of wild fish consumption for various species in Alaska
      reveals shortcomings in data and monitoring needs.
AB  - Northern peoples face a difficult decision of whether or not to consume wild
      fish, which may contain dangerous levels of contaminants such as methylmercury
      (MeHg), but which also offer a number of positive health benefits, and play an
      important role in rural household economies. Here, new methods for developing
      consumption advice are applied to an existing data-set for methylmercury (MeHg)
      levels in Alaskan fish. We apply a quantitative risk-benefit analysis for eight
      freshwater, saltwater and anadromous fish species, using dose-response
      relationships to weigh the risks of MeHg bioaccumulation against the benefits of
      omega-3 fatty acids (EPA and DHA) toward cardiovascular and neurodevelopmental
      health endpoints. Findings suggests that consumption of many of the fish species
      reviewed here, including northern pike, Pacific Halibut, and arctic grayling, may
      lead to increased risk of coronary heart disease and declines in infant visual
      recognition memory. However, we also identify significant variation among
      regions, among studies within the same region, and also within studies, which
      make it difficult to craft consistent consumption advice. Whereas salmon
      consistently shows a net-benefit, for instance, data for arctic grayling, pike,
      sablefish, and some halibut are all too imprecise to provide consistent
      recommendations. We argue for more detailed local-scale monitoring, and
      identification of possible thresholds for increased risk in the future. We
      caution that MeHg and omega-3 FA are just two variables in a complicated calculus
      for weighing the risks and benefits of locally-available and culturally
      significant foods, and argue for future work that takes both a place-based and
      plate-based approach to diet and contamination.

PMID- 20673962
TI  - In vitro evaluation of the cytotoxicity of iron oxide nanoparticles with
      different coatings and different sizes in A3 human T lymphocytes.
AB  - The ever expanding use of engineered nanoscaled materials has brought about a
      commensurate growth in concern about their potential risks to human and
      environmental health. Toxicity of nanoparticles could vary with their
      physicochemical parameters. The dependence of cytotoxicity on particle size and
      surface coating of iron oxide nanoparticles was investigated in this in vitro
      study using the A3 human T lymphocyte as a model. Two different sizes (10 nm and
      50 nm) and two different surface coatings (amine and carboxyl groups) of iron
      oxide (IO) nanoparticles were tested with fluorescein diacetate (FDA) assay and
      WST-1 assay. In the 1-h FDA assay with PBS, IO nanoparticles did not show size
      dependent toxicity to A3 cells in terms of mass concentration; however, in terms
      of the number of particles per well and the total surface area, they did exhibit
      size-dependent toxicity. Fifty nanometer IO nanoparticles are more toxic than the
      10 nm counterparts. The results of both the 24-h FDA and WST-1 assays in a
      complete growth medium indicate size- and surface coating-dependent toxicity to
      A3 cells in terms of mass concentration. IO nanoparticles of the smaller size are
      more toxic than those of the larger size. IO nanoparticles with the carboxyl
      group have a higher toxicity than those with the amine group. However, in the 24
      h FDA assay, in terms of the number of particles per well and the resultant total
      surface area per well, the 50 nm IO nanoparticles are more toxic than those of
      size 10 nm. In terms of mass concentration, the number of particles per well and
      the total surface area, both of the 24-h assays showed the consistent results
      that IO nanoparticles with the carboxyl group have a higher toxicity than those
      with the amine group.

PMID- 20673963
TI  - Formation of metacinnabar by milling of liquid mercury and elemental sulfur for
      long term mercury storage.
AB  - In this paper we present the results of the formation of black HgS (metacinnabar)
      from liquid mercury and elemental sulfur using the mechanical energy provided by
      a ball mill in different conditions. Metacinnabar formation was observed even
      after short milling times (15 min) and unreacted liquid mercury was no longer
      detected after 60 min of milling. The reaction mechanism was monitored with a
      scanning electron microscope. The impact and friction forces of milling on the Hg
      and S mixture resulted in the formation of metacinnabar by reducing the size of
      mercury drops, giving rise to microspheres, and lowering the surface tension to
      allow sulfur grains to become adhered at the reaction interface. After 60 min of
      milling, the metacinnabar formation reaction was observed to be more than 99.99%
      complete, yielding a Toxicity Characteristic Leaching Procedure value of 3.1
      microg/L Hg. The reaction product thus complies with the limits of the most
      stringent Universal Treatment Standard requirements, which allow a maximum TCLP
      concentration of 25 microg/L.

PMID- 20673964
TI  - Prioritization of sediment management alternatives using stochastic multicriteria
      acceptability analysis.
AB  - Decision-making for sediment management is a complex task that requires the
      consideration of temporal and spatial impacts of several remedial alternatives as
      well as the associated economic, social and political impact. Multicriteria
      decision analysis (MCDA) is becoming increasingly recognized as an important
      environmental management tool that can be used to support the selection of
      suitable remediation alternatives and prioritization of management units in space
      and time. This paper proposes an MCDA framework for prioritizing sediment
      management alternatives. This framework involves identifying of a set of feasible
      options, as well as defining and evaluating criteria which integrate relevant
      technical, economic, social and environmental aspects of remedies. The
      methodology allows an explicit consideration of uncertainty in criteria scores
      and weights by assigning probability distributions and analyzing subsequent Monte
      Carlo simulations. The consideration of different stakeholder simulated values is
      used to assess the robustness of alternative rankings and to guide the selection
      of remediation options. An application of this methodology to a case study in the
      Bay of Santander, Spain, is presented. An assessment is conducted for the case of
      unknown preferences as well as for hypothetical preferences profiles for four
      types of stakeholders: Idealist, Politician, Environmentalist and Balanced. The
      results are used to visualize stakeholder positions and potential disagreements,
      allowing for the identification of a group of least preferred alternatives for
      each stakeholder. Stakeholder involvement has the potential to ease the remedy
      selection process during all stages of the decision-making process and to
      eventually remedy implementation.

PMID- 20673965
TI  - The use of modelling to predict levels of estrogens in a river catchment: how
      does modelled data compare with chemical analysis and in vitro yeast assay
      results?
AB  - Effluent discharges at Rodbourne sewage treatment works (STWs) were assessed
      using chemical and in vitro biological analysis as well as modelling predictions.
      Results showed that Rodbourne STW discharged less estrone (E1) than expected, but
      similar 17beta-estradiol (E2) and 17alpha-ethinyl estradiol (EE2) to those
      predicted by a widely cited effluent prediction model. The Exposure Analysis
      Modelling System (EXAMS) model was set up using measured effluent concentrations
      as its starting point to predict estrogen concentrations along a 10 km length of
      the receiving water of the River Ray. The model adequately simulated estrogen
      concentrations along the river when compared to July 2007 measured data. The
      model predicted combined estrogen equivalents in reasonable agreement with
      estrogenicity as measured by passive sampler (POCIS) extracts using the yeast
      estrogen screen. Using gauged mean flow values for 2007 the model indicated that
      the most important determinand for estrogen exposure in the Ray was not season,
      but proximity to the Rodbourne effluent. Thus, fish in the first 3 km downstream
      of Rodbourne were typically exposed to two or even three times more estrogens
      than those living 7-10 km further downstream. The modelling indicated that,
      assuming the effluent estrogen concentrations measured in February 2008 were
      typical, throughout the year the whole length of the Ray downstream of Rodbourne
      would be estrogenic, i.e. exceeding the 1 ng/L E2 equivalent threshold for
      endocrine disruption.

PMID- 20673966
TI  - Long-term monitoring (1960-2008) of the river-sediment transport in the Red River
      Watershed (Vietnam): temporal variability and dam-reservoir impact.
AB  - The Red River (China/Vietnam, A=155,000 km(2)) is a typical humid tropics river
      originating from the mountainous area of Yunnan Province in China. Based on
      information on daily discharge (Q) and suspended particulate matter (SPM)
      concentration between 1960-2008 for the SonTay gauging station (outlet of the
      River and entry to the Delta) provided by the National Institute IMHE-MONRE, the
      mean annual SPM flux was estimated at 90 Mt/yr, corresponding to a sediment yield
      of 600 t/km(2)/yr. The temporal variability of annual SPM fluxes (ranging from 24
      to 200 Mt/yr) is strongly related to the interannual hydrological conditions.
      However, some years of high water flow were not associated with high sediment
      fluxes, especially after 1989 when the HoaBinh dam came into operation.
      Therefore, the median discharge pre- (3389 m(3)/s) and post 1989 (3495 m(3)/s)
      are similar indicating there was little or no change between both periods.
      Sediment rating curves (power law-type; SPM=aQ(b)) were fitted for both periods
      (1960-1989; 1990-2008). The analysis of the pre- and post-1989 sediment rating
      parameters (a, b) suggests a downshift of b-parameter values after 1989,
      attributed to a decrease of the sediment supply due to the commissioning of the
      HoaBinh dam. A single sediment rating curve derived from 1960-1989 data was used
      to simulate the annual variability of former sediment delivery, generating
      excellent cumulative flux estimates (error ~1%). In contrast, applying the same
      rating curve to the 1990-2008 data resulted in systematic and substantial (up to
      109%) overestimation. This suggests that the HoaBinh dam reduces annual SPM
      delivery to the delta by half, implying important metal/metalloid storage behind
      the HoaBinh dam.

PMID- 20673967
TI  - TAPIR--Finnish national geochemical baseline database.
AB  - In Finland, a Government Decree on the Assessment of Soil Contamination and
      Remediation Needs has generated a need for reliable and readily accessible data
      on geochemical baseline concentrations in Finnish soils. According to the Decree,
      baseline concentrations, referring both to the natural geological background
      concentrations and the diffuse anthropogenic input of substances, shall be taken
      into account in the soil contamination assessment process. This baseline
      information is provided in a national geochemical baseline database, TAPIR, that
      is publicly available via the Internet. Geochemical provinces with elevated
      baseline concentrations were delineated to provide regional geochemical baseline
      values. The nationwide geochemical datasets were used to divide Finland into
      geochemical provinces. Several metals (Co, Cr, Cu, Ni, V, and Zn) showed
      anomalous concentrations in seven regions that were defined as metal provinces.
      Arsenic did not follow a similar distribution to any other elements, and four
      arsenic provinces were separately determined. Nationwide geochemical datasets
      were not available for some other important elements such as Cd and Pb. Although
      these elements are included in the TAPIR system, their distribution does not
      necessarily follow the ones pre-defined for metal and arsenic provinces. Regional
      geochemical baseline values, presented as upper limit of geochemical variation
      within the region, can be used as trigger values to assess potential soil
      contamination. Baseline values have also been used to determine upper and lower
      guideline values that must be taken into account as a tool in basic risk
      assessment. If regional geochemical baseline values are available, the national
      guideline values prescribed in the Decree based on ecological risks can be
      modified accordingly. The national geochemical baseline database provides
      scientifically sound, easily accessible and generally accepted information on the
      baseline values, and it can be used in various environmental applications.

PMID- 20673968
TI  - Do the VOCs that evaporate from a heavily polluted river threaten the health of
      riparian residents?
AB  - To understand the potential threat of volatile organic compounds (VOCs) to the
      health of residents living close to a heavily polluted river, this study
      investigated the species and the concentration of VOCs evaporating from a river
      and surveyed the health condition of the nearby residents. Air samples were taken
      seasonally at the upstream, midstream, and downstream water surfaces of the
      river, and at different locations at certain distances from the river. These
      samples were analyzed qualitatively and quantitatively through gas chromatography
      and electron capture detector (GC/ECD) for chlorinated organic compounds, and
      through gas chromatography and flame ionization detector (GC/FID) for ordinary
      hydrocarbons. The health data obtained from valid health questionnaires of 908
      residents were analyzed through Statistical Package for Social Science (SPSS)
      software. Twenty-six species of VOCs were identified in the environment adjacent
      the river, many of which are carcinogenic or believed to be carcinogenic to
      humans. However, results of this study shows that the VOCs evaporating from the
      polluted river have not been definitively identified as a major factor of cancer
      in the residents. However, the risk of suffering from certain chronic diseases
      may increase in residents living less than 225 m away from the river due to the
      high levels of evaporated VOCs. Residents living less than 225 m away from the
      river and with nearby specific industries are 3.130 times more at risk of
      suffering from chronic diseases than those with no nearby specific industries.

PMID- 20673969
TI  - Enhanced hemostatic indices in patients with pulmonary arterial hypertension: an
      observational study.
AB  - BACKGROUND: Pulmonary arterial hypertension (PAH) is a chronic progressive
      disease characterized by persistent elevation of pulmonary artery pressure.
      Regardless of the initial trigger, the elevated pulmonary arterial pressure and
      vascular resistance in patients with PAH are primarily caused by remodeling and
      thrombosis of small- and medium-sized pulmonary arteries and arterioles, as well
      as sustained vasoconstriction. Recent studies have emphasized the relevance of
      several biomarkers of hemostasis in the PAH progression. However, there is no
      agreement whether hemostatic indices are indeed distinguishing PAH patients from
      controls. METHODS: Plasma fibrinogen, D-dimer, platelet count, and mean platelet
      volume, and platelet aggregation induced by ADP and collagen were serially
      measured in 34 patients with PAH, and 34 matched by age and sex normal
      volunteers. RESULTS: Hemostatic indices were significantly higher for fibrinogen
      (p=0.0001), D-dimer (p=0.001), mean platelet volume (p=0.001), and platelet
      aggregation induced by ADP-, and collagen (p=0.0001 for both) in PAH patients
      when compared to healthy controls. In contrast, platelet counts were almost
      identical between both groups. CONCLUSIONS: Patients with PAH exhibit activation
      of hemostatic indices compared to healthy controls. These data support previous
      observations that hemostatic abnormalities including platelet activation may
      directly impact pathogenesis of PAH, and need to be confirmed in larger
      randomized studies with more comprehensive assessment of hemostatic indices for
      justification of antithrombotic strategies.

PMID- 20673970
TI  - The role of neoadjuvant chemotherapy in the management of patients with advanced
      stage ovarian cancer: survey results from members of the Society of Gynecologic
      Oncologists.
AB  - OBJECTIVE: Recent randomized controlled data suggest that neoadjuvant
      chemotherapy (NACT) with interval debulking (ID) may produce similar overall
      survival and progression free survival compared to standard primary cytoreduction
      followed by chemotherapy. The object of our study was to assess current patterns
      of care among members of the Society of Gynecologic Oncologists (SGO),
      specifically collating their opinions on and use of NACT for advanced stage
      ovarian cancer. METHODS: A 20-item questionnaire was sent to all working e-mail
      addresses of SGO members (n=1137). The data was collected and analyzed using
      descriptive statistics with commercially available online survey software. The
      Chi-square test for independence was used to determine differences in responses
      between groups. RESULTS: Of 339 (30%) responding members, most rarely employ
      NACT, with 60% of respondents using NACT in less than 10% of advanced stage
      ovarian cancer cases. Respondents did not consider available evidence sufficient
      to justify NACT followed by ID (82%), nor did most think it should be preferred
      (74%). Sixty-two percent of respondents thought it was impossible to accurately
      predict preoperatively whether an optimal cytoreduction is possible. Thirty-nine
      percent believed that women with bulky upper abdominal disease on preoperative
      imaging would benefit from NACT versus primary debulking. If gross disease were
      found at ID, 43% would continue to treat with IV chemotherapy, and 42% would
      place an IP port if optimally cytoreduced. When ID reveals microscopic disease,
      51% would continue IV treatment and the remaining IP therapy. Eighty-six percent
      of the respondents believed that both biological and surgical factors determine
      patient outcomes. CONCLUSIONS: The majority of responding SGO members do not
      treat patients with NACT followed by ID. Currently available studies of NACT/ID
      have been insufficient to convince most gynecologic oncologists to incorporate it
      into practice. Our results provide a benchmark against which further research can
      assess the penetration of NACT/ID into clinical practice.

PMID- 20673971
TI  - Laparoscopic nerve-sparing radical hysterectomy with fascia space dissection
      technique for cervical cancer: description of technique and outcomes.
AB  - OBJECTIVES: The objectives of this study were to describe our laparoscopic nerve
      sparing radical hysterectomy (LNSRH) technique and to assess the feasibility and
      safety of the procedure, as well as its impact on voiding function. We introduce
      a fascia space dissection technique in order to preserve the pelvic splanchnic
      nerve, the hypogastric nerve and the bladder branch of the inferior hypogastric
      plexus under magnification (*10.5) during laparoscopic radical hysterectomy (LRH)
      with pelvic lymphadenectomy. METHODS: From October 2006 to November 2009, 163
      consecutive patients with cervical cancer underwent laparoscopic radical
      hysterectomy (LRH) and pelvic lymphadenectomy, with 82 women undergoing LNSRH
      with fascia space dissection technique (LNSRH group) and 81 undergoing LRH (LRH
      group). Data from 163 patients were prospectively collected and compared. Post
      operative assessment of bladder function included the following: the time to
      recover the ability to void spontaneously and to achieve a post-void residual
      urine (PVR) volume of less than 50 ml, with urination function graded. RESULTS:
      The laparoscopic nerve-sparing radical hysterectomy procedure was completed
      successfully and was conducted safely in all of the patients. There were no
      conversions to open surgery in the two groups. The median operative duration in
      the LNSRH and the LRH groups were 163.52+/-34.47 min and 132.13+/-31.42 min,
      respectively. Blood loss was 142.12+/-62.38 ml and 187.69+/-68.63 ml,
      respectively. The time taken to obtain a post-void residual urine volume of less
      than 50 ml after removal of the urethral catheter was 7.42+/-2.35 d (5-18 d) in
      LNSRH group and was 16.75+/-7.73 d (5-35 d) in LRH group (P<0.05). The bladder
      void function recovery to Grades 0-I was 76 (92.7%) for the LNSRH group and 59
      (72.8%) for the LRH group. A mean follow-up of 22.3 (5-42) months was adhered to,
      and no patient had a recurrence or metastasis. CONCLUSIONS: The technique
      described in this preliminary study appears to be safe, feasible, and easy in our
      population, with satisfactory recovery of voiding function.

PMID- 20673972
TI  - Learning about ovarian cancer at the time of diagnosis: video versus usual care.
AB  - OBJECTIVE: Effective patient -clinician communication at diagnosis is important,
      yet decreased provider time for face-to-face interactions makes traditional
      paradigms in cancer care difficult. We evaluated the effects of an educational
      video on patients' distress, cancer knowledge, coping skills and attitudes
      regarding learning about cancer at the time of ovarian cancer diagnosis. METHODS:
      An educational video was developed in which oncology professionals, women with
      ovarian cancer, and their relatives discussed cancer information and experiences.
      Women admitted for initial diagnostic surgical staging for ovarian cancer were
      randomized to the educational or placebo video. Before and after the video,
      patients completed measures of (1) ovarian cancer information, (2) emotional
      distress, (3) learning attitudes, and (4) coping self-efficacy. Outcomes were
      analyzed for differences in mean change between intervention and placebo groups
      using t-tests. RESULTS: Fifty-nine subjects were randomized (30 intervention/29
      placebo). The majority were advanced staged, white, insured, high school
      educated, employed, and rated their disease seriousness as high. Anxiety, general
      distress and cancer-specific distress were high. Pre-post video: distress and
      self-efficacy between groups were unchanged, intervention subjects answered more
      knowledge items correctly (p=0.0004) and developed more negative learning
      attitudes (p=0.037). Following the educational video, patients who developed more
      negative attitudes also had increased intrusive thinking (p=0.046), a sign of
      increased distress. CONCLUSIONS: Video presentation of cancer-related information
      increases learning under conditions of high distress and disease threat however,
      it is not without risk for some. Differing information needs may affect women's
      emotional response under these conditions.

PMID- 20673973
TI  - Lymph nodes: is total number or station number a better predictor of lymph node
      metastasis in endometrial cancer?
AB  - OBJECTIVE: Gynecologic oncologists have sought to define adequate
      lymphadenectomy. The purpose of this study is to determine the probability of
      detecting lymph node metastasis by lymph node count compared to number of nodal
      stations sampled. METHODS: This is a clinicopathologic review of surgically
      staged endometrial carcinoma patients from 2000 to 2008. Information was
      extracted from patients' medical records. Student t-test, Wilcoxon rank sum test,
      Chi-square and Fisher exact tests were used. Elimination logistic regression was
      performed to identify independent significant predictors of lymph node
      metastasis. p<.05 was considered significant for all tests. RESULTS: The study
      population consisted of 352 patients with a mean age of 65. Forty patients
      (11.36%) had lymph node metastasis. Number of nodes sampled was not associated
      with lymph node status on univariate analyses. Patients with lymph node
      metastases detected was increased when 8 or more nodal stations were sampled
      compared to less than 8 (19.4% vs. 9.8%, p=.04). More significance was seen when
      9 or more stations were sampled (32% vs. 9.8%, p=.004). Multivariate logistic
      regression analysis, controlling for age, grade, depth of myometrial invasion,
      number of nodes sampled, and number of nodal stations sampled, found only grade
      (p=.002), depth of myometrial invasion (p<.0003), and sampling of 9 or more nodal
      stations (p=.03) to be independent predictors of node status. CONCLUSIONS: Lymph
      node count did not accurately predict risk of lymph node metastasis. Number of
      nodal stations sampled was a more precise predictor of lymph node metastases.

PMID- 20673974
TI  - Upstaging pathologic stage I ovarian carcinoma based on dense adhesions is not
      warranted: a clinicopathologic study of 84 patients originally classified as FIGO
      stage II.
AB  - BACKGROUND: FIGO stage II ovarian cancer comprises 8% of ovarian cancers. It is a
      common but not universal practice to upstage densely adherent pathologic stage I
      tumors to stage II. FIGO guidelines are not clear, and data supporting this
      practice are sparse. METHODS: We retrospectively reviewed patients with stage II
      ovarian cancer and grouped them based upon histologic evidence of extraovarian
      extension. Tumors densely adherent to extraovarian structures but without
      histologic tumor outside the ovary were considered pathologic stage I. All others
      were considered surgical-pathologic stage II. Three histologic patterns of
      extraovarian tumor involvement were identified. RESULTS: Eighty-four patients
      were studied. Twenty-four patients had pathologic stage I disease and 60 had
      histologic evidence of extraovarian pelvic spread and were surgical-pathologic
      stage II. The 5-year survival for stage I was 100%, and the median survival was
      not reached. The 5-year survival for those with surgical-pathologic stage II
      disease was 56.8% and the median survival was 73 months. There were no
      differences observed based upon pattern of extraovarian spread. The survival
      difference between pathologic stage I and surgical-pathologic stage II was
      significant (p<0.001). There were no differences seen in 5-year survival among
      surgical-pathologic stage II patients with serous, endometrioid or clear cell
      histologies (64.5%, 64.8% and 64.3% respectively). CONCLUSION: These
      retrospective data suggest that the practice of upstaging densely adherent
      pathologic stage I tumors to stage II may not be warranted. Cell type is not a
      prognostic factor in stage II.

PMID- 20673975
TI  - In vitro and in vivo histone deacetylase inhibitor therapy with vorinostat and
      paclitaxel in ovarian cancer models: does timing matter?
AB  - OBJECTIVE: To determine whether the combination of vorinostat (suberoylanilide
      hydroxamic acid, SAHA) and paclitaxel is more effective than either individual
      agent and to evaluate the effect of drug sequencing in ovarian cancer cell lines
      and in mouse models. METHODS: For in vitro studies, three ovarian cancer cell
      lines (2774, SKOV-3 and OVCAR-3) were grown with either 10 nM paclitaxel, or
      vorinostat (0.3, 1, 3 or 10 MUM), or vehicle (DMSO) and subsequently treated with
      10 nM paclitaxel, or vorinostat (0.3, 1, 3, or 10 MUM), or DMSO. Apoptosis was
      analyzed. In the mouse, treatments were given for a total of 5 weeks: vehicle
      control, paclitaxel, vorinostat, vorinostat followed by paclitaxel, paclitaxel
      followed by vorinostat, and simultaneous vorinostat and paclitaxel. Endpoints
      were survival, ascites and tumor weight. Protein expression was analyzed by
      Western blots. RESULTS: In two cell lines (SKOV-3, OVCAR-3), the sequence of
      vorinostat and paclitaxel administration did not significantly alter the
      apoptosis percentages and the combination was not superior to individual agents.
      However, in one cell line (2774), the most effective combination in achieving
      apoptosis was paclitaxel followed by low dose vorinostat. In the mouse model,
      both control and vorinostat alone treatment groups were inferior to paclitaxel
      and the combination treatment groups, but no significant differences were
      observed between the groups receiving both paclitaxel and vorinostat based on the
      sequence of administration. CONCLUSIONS: The efficacy of the combination and
      sequence of vorinostat and paclitaxel administration was cell line dependent and
      suggests that responses vary based on tumor specific characteristics.

PMID- 20673976
TI  - Higher sensitivity to patupilone versus paclitaxel chemotherapy in primary
      uterine serous papillary carcinoma cell lines with high versus low HER-2/neu
      expression in vitro.
AB  - OBJECTIVE: To compare the in vitro sensitivity/resistance to patupilone versus
      paclitaxel in uterine serous papillary carcinoma (USPC) with high versus low HER
      2/neu expression. METHODS: Six primary USPC cell lines, half of which overexpress
      HER-2/neu at a 3+ level, were evaluated for growth rate and tested for their in
      vitro sensitivity/resistance to patupilone versus paclitaxel by MTS assays.
      Quantitative RT-PCR was used to identify potential mechanisms underlying the
      differential sensitivity/resistance to patupilone versus paclitaxel in primary
      USPC cell lines. RESULTS: Cell lines overexpressing HER-2/neu showed higher
      proliferation when compared to low HER-2/neu-expressing cell lines. Compared to
      low-expressing cell lines, high HER-2/neu expressors were significantly more
      sensitive to patupilone than to paclitaxel (P<0.0002). In contrast, there was no
      appreciable difference in sensitivity to patupilone versus paclitaxel in primary
      USPC cell lines with low HER-2/neu expression. Higher levels of beta-tubulin III
      (TUBB3) and P-glycoprotein (ABCB1) were detected in USPC cell lines with high
      versus low HER-2/neu expression (P<0.05). CONCLUSIONS: USPC overexpressing HER
      2/neu display greater in vitro sensitivity to patupilone and higher levels of the
      patupilone molecular target TUBB3 when compared to low HER-2/neu expressors. Due
      to the adverse prognosis associated with HER-2/neu overexpression in USPC
      patients, patupilone may represent a promising novel drug to combine to platinum
      compounds in this subset of aggressive endometrial tumors.

PMID- 20673977
TI  - Successful use of omalizumab for prevention of fire ant anaphylaxis.

PMID- 20673978
TI  - Interferon response factor 3 is essential for house dust mite-induced airway
      allergy.
AB  - BACKGROUND: Pattern-recognition receptors (PRRs) are critically involved in the
      pathophysiology of airway allergy, yet most of the signaling pathways downstream
      of PRRs implicated in allergic airway sensitization remain unknown. OBJECTIVE: We
      sought to study the effects of genetic depletion of interferon response factor
      (IRF) 3 and IRF7, important transcription factors downstream of various PRRs, in
      a murine model of house dust mite (HDM)-induced allergic asthma. METHODS: We
      compared HDM-induced allergic immune responses in IRF3-deficient (IRF3(-/-)),
      IRF7(-/-), and wild-type mice. RESULTS: Parameters of airway allergy caused by
      HDM exposure were strongly attenuated in IRF3(-/-), but not IRF7(-/-), mice
      compared with those in wild-type mice. Indeed, in HDM-exposed IRF3(-/-) mice HDM
      specific T(H)2 cell responses did not develop. This correlated with impaired
      maturation and migration of IRF3(-/-) lung dendritic cells (DCs) on HDM
      treatment. Furthermore, adoptive transfer of HDM-loaded DCs indicated that IRF3(
      /-) DCs had an intrinsic defect rendering them unable to migrate and to prime HDM
      specific T(H)2 responses. Intriguingly, we also show that DC function and
      allergic airway sensitization in response to HDM were independent of signaling by
      type I interferons, the main target genes of IRF3. CONCLUSION: Through its role
      in DC function, IRF3, mainly known as a central activator of antiviral immunity,
      is essential for the development of T(H)2-type responses to airway allergens.

PMID- 20673979
TI  - Nasal application of rBet v 1 or non-IgE-reactive T-cell epitope-containing rBet
      v 1 fragments has different effects on systemic allergen-specific antibody
      responses.

PMID- 20673980
TI  - Ciliary dysfunction and ultrastructural abnormalities are features of severe
      asthma.
AB  - BACKGROUND: Epithelial dysfunction has been implicated in asthma pathophysiology,
      but no studies have directly assessed ciliary function in asthma. OBJECTIVE: To
      study the ciliary function and epithelial ultrastructure of patients with asthma
      and healthy controls. METHODS: We studied ciliary beat frequency and beat pattern
      by using digital high-speed video imaging and ultrastructure by transmission
      electron microscopy of bronchial epithelial strips from 7 subjects with mild, 7
      with moderate, and 19 with severe asthma and 9 healthy controls. RESULTS: The
      median (interquartile range) ciliary beat frequency was decreased in moderate
      (6.5 [4.4-8.5] Hz) and severe asthma (6.7 [6.1-7.6] Hz) compared with controls
      (10.5 [9.7-11.8] Hz; P < .01). Dyskinesia and immotility indices were higher in
      severe asthma (65% [43%-75%]; 6.3% [1%-9.5%], respectively) compared with
      controls (4% [0%-6.7%; 0%, respectively; P < .01). These abnormalities were
      related to disease severity (ciliary beat frequency, r(s) = -0.68; dyskinesia
      index, r(s) = 0.86; immotility index, r(s) = 0.65; P < .0001). The ultrastructure
      of the epithelium was abnormal in severe asthma with a reduction in ciliated
      cells, an increase in dead cells, and ciliary disorientation compared with all
      other groups (P < .05). Compared with patients with mild asthma and healthy
      controls, patients with severe asthma showed increased ciliary depletion,
      microtubular defects, mitochondrial damage, and cytoplasmic blebbing (P < .01).
      All of these changes were related to disease severity. CONCLUSION: Ciliary
      dysfunction and ultrastructural abnormalities are closely related to asthma
      severity. Ciliary dysfunction is a feature of moderate to severe asthma, and
      profound ultrastructural abnormalities are restricted to severe disease. Whether
      these changes contribute to the development of severe asthma phenotype remains to
      be determined.

PMID- 20673981
TI  - Effective treatment of therapy-resistant chronic spontaneous urticaria with
      omalizumab.

PMID- 20673982
TI  - Genetic influence on the age at onset of asthma: a twin study.
AB  - BACKGROUND: Although the genetics of asthma susceptibility have been frequently
      explored, little is known about genetic factors that influence the age at onset
      of asthma. OBJECTIVE: To study the variation in the age at onset of asthma
      attributable to genetic and environmental factors. METHODS: Data on the age at
      onset and predictors of asthma were collected in 2002 via a multidisciplinary
      questionnaire study of 34,782 Danish twins 20 to 71 years of age. Survival
      analytic methods were applied to partition variation in the age at onset of
      asthma into genetic and environmental components. RESULTS: Sex, hay fever, atopic
      dermatitis, smoking, and exposure to passive smoking in childhood were
      significant risk factors, whereas BCG vaccination was protective for asthma. The
      risk of asthma in the co-twin of an affected twin was higher in monozygotic than
      in dizygotic twins (hazard ratio, 2.59; 95% CI, 1.83-3.68; P < .001). The risk of
      asthma in the co-twin decreased with increasing age at onset of asthma in the
      index twin (hazard ratio per ten years, 0.86; 95% CI, 0.76-0.98; P = .019). The
      effect was attenuated in dizygotic twins relative to monozygotic twins (P =
      .005). Genetic factors explained 34% of the variation in the age at onset of
      asthma, and environmental factors accounted for 66%. CONCLUSION: Host-related
      differences in genetic makeup cause different individuals to develop asthma at
      different ages. Better understanding of the causes for variation in the age at
      onset of disease may ultimately lead the way to targeted treatments.

PMID- 20673985
TI  - Asthma in the elderly: diagnosis and management.
AB  - The National Asthma Education and Prevention Program's "Expert Panel Report 3:
      Guidelines for the Diagnosis and Management of Asthma" apply to all ages. This
      review discusses additional specific points for elderly patients. These patients
      are very heterogeneous. Their asthma can have begun at any time and can vary
      greatly in severity. It is frequently associated not only with any of the
      diseases that affect older persons but also with comorbid lung diseases. Many
      patients have irreversible airway obstruction, which is due to severe airway
      remodeling, chronic obstructive pulmonary disease, or bronchiectasis. Diagnosis
      should include chest radiography and computed tomographic scanning to diagnose
      other lung diseases if FEV1 remains low after treatment. Asthma pathogenesis
      includes not only IgE-mediated allergy but also innate immune inflammation from
      endotoxin and trypsin-like proteases, and therefore evaluation and control of
      environmental exposures is an important part of management. Pharmacologic
      treatment, too, is adjusted to achieve and maintain control and is basically the
      same for all ages, except that elderly patients have reduced response to
      bronchodilators and increased side effects from beta adrenergic agonists and
      glucocorticoids. Many elderly patients have difficulty inhaling aerosols, and
      therefore nebulizers might be a better delivery system. Oral medications have the
      benefit of greater ease of administration and greater efficacy on the peripheral
      airways. Leukotriene antagonists and low-dose theophylline are often helpful
      additives to aerosol glucocorticoids. Oral glucocorticoids might be indicated for
      severe asthma.

PMID- 20673984
TI  - Dual-specificity phosphatase 1 as a pharmacogenetic modifier of inhaled steroid
      response among asthmatic patients.
AB  - BACKGROUND: Inhaled corticosteroids (ICSs) are considered first-line treatment
      for persistent asthma, yet there is significant variability in treatment
      response. Dual-specificity phosphatase 1 (DUSP1) appears to mediate the anti
      inflammatory action of corticosteroids. OBJECTIVE: We sought to determine whether
      variants in the DUSP1 gene are associated with clinical response to ICS
      treatment. METHODS: Study participants with asthma were drawn from the following
      multiethnic cohorts: the Genetics of Asthma in Latino Americans (GALA) study; the
      Study of African Americans, Asthma, Genes & Environments (SAGE); and the Study of
      Asthma Phenotypes and Pharmacogenomic Interactions by Race-ethnicity (SAPPHIRE).
      We screened GALA study participants for genetic variants that modified the
      relationship between ICS use and bronchodilator response. We then replicated our
      findings in SAGE and SAPPHIRE participants. In a group of SAPPHIRE participants
      treated with ICSs for 6 weeks, we examined whether a DUSP1 polymorphism was
      associated with changes in FEV(1) and self-reported asthma control. RESULTS: The
      DUSP1 polymorphisms rs881152 and rs34507926 localized to different haplotype
      blocks and appeared to significantly modify the relationship between ICS use and
      bronchodilator response among GALA study participants. This interaction was also
      seen for rs881152 among SAPPHIRE but not SAGE participants. Among the group of
      SAPPHIRE participants prospectively treated with ICSs for 6 weeks, rs881152
      genotype was significantly associated with changes in self-reported asthma
      control but not FEV(1). CONCLUSION: DUSP1 polymorphisms were associated with
      clinical response to ICS therapy and therefore might be useful in the future to
      identify asthmatic patients more likely to respond to this controller treatment.

PMID- 20673986
TI  - Resurrection men and the FEF25-75.

PMID- 20673987
TI  - Transplantation of hematopoietic stem cells and long-term survival for primary
      immunodeficiencies in Europe: entering a new century, do we do better?
AB  - BACKGROUND: Hematopoietic stem cell transplantation remains the only treatment
      for most patients with severe combined immunodeficiencies (SCIDs) or other
      primary immunodeficiencies (non-SCID PIDs). OBJECTIVE: To analyze the long-term
      outcome of patients with SCID and non-SCID PID from European centers treated
      between 1968 and 2005. METHODS: The product-limit method estimated cumulative
      survival; the log-rank test compared survival between groups. A Cox proportional
      hazard model evaluated the impact of independent predictors on patient survival.
      RESULTS: In patients with SCID, survival with genoidentical donors (n = 25) from
      2000 to 2005 was 90%. Survival using a mismatched relative (n = 96) has improved
      (66%), similar to that using an unrelated donor (n = 46; 69%; P = .005).
      Transplantation after year 1995, a younger age, B(+) phenotype, genoidentical and
      phenoidentical donors, absence of respiratory impairment, or viral infection
      before transplantation were associated with better prognosis on multivariate
      analysis. For non-SCID PID, in contrast with patients with SCID, we confirm that,
      in the 2000 to 2005 period, using an unrelated donor (n = 124) gave a 3-year
      survival rate similar to a genoidentical donor (n = 73), 79% for both. Survival
      was 76% in phenoidentical transplants (n = 23) and worse in mismatched related
      donor transplants (n = 47; 46%; P = .016). CONCLUSION: This is the largest cohort
      study of such patients with the longest follow-up. Specific issues arise for
      different patient groups. Patients with B-SCID have worse survival than other
      patients with SCID, despite improvements in each group. For non-SCID PID,
      survival is worse than SCID, although more conditions are now treated. Individual
      disease categories now need to be analyzed so that disease-specific prognosis may
      be better understood and the best treatments planned.

PMID- 20673988
TI  - Serum amyloid P attenuates M2 macrophage activation and protects against fungal
      spore-induced allergic airway disease.
AB  - BACKGROUND: Aspergillus fumigatus conidia aggravate asthmatic responses. Lung
      macrophages normally kill fungal conidia, but the presence of type 2 cytokines
      during asthma contributes to the alternative (or M2) activation of these cells,
      which secrete proallergic factors and exhibit impaired innate immunity.
      OBJECTIVE: Considering that pentraxins modulate macrophage function, we examined
      the effect of C-reactive protein (CRP) and serum amyloid P (SAP) in an
      experimental model of A fumigatus-induced allergic airway disease. METHODS: The
      effects of SAP and CRP on M2 macrophage differentiation were examined in vitro,
      and the in vivo effects of these pentraxins were analyzed in the asthma model.
      RESULTS: SAP inhibited the generation of M2 markers, such as arginase and the
      chitinase Ym-1, through an FcgammaR-dependent mechanism in cultured macrophages.
      This effect correlated with a decrease in signal transducer and activator of
      transcription 6 (STAT6) phosphorylation in SAP-treated M2 macrophages. In vivo
      treatment with SAP significantly decreased methacholine-induced bronchial
      resistance, mucus cell metaplasia, the number of "found in inflammatory zone 1"
      (FIZZ1)-positive cells in the lungs, and collagen deposition compared with the
      control group. CRP had a modest effect on M2 differentiation, and in vivo
      treatment with CRP had a minor effect or exacerbated A fumigatus-induced lung
      disease. Finally, the adoptive transfer of SAP-pretreated M2 macrophages into
      allergic mice significantly attenuated disease when compared with nontransferred
      or M2-transferred control groups. CONCLUSIONS: These findings demonstrate that
      SAP is a potent inhibitor of M2 macrophage differentiation and represents a novel
      therapy in A fumigatus-induced allergic disease.

PMID- 20673983
TI  - In utero smoke exposure and impaired response to inhaled corticosteroids in
      children with asthma.
AB  - BACKGROUND: Few studies have examined the effects of in utero smoke exposure
      (IUS) on lung function in children with asthma, and there are no published data
      on the impact of IUS on treatment outcomes in children with asthma. OBJECTIVES:
      To explore whether IUS exposure is associated with increased airway
      responsiveness among children with asthma and whether IUS modifies the response
      to treatment with inhaled corticosteroids (ICSs). METHODS: To assess the impact
      of parent-reported IUS exposure on airway responsiveness in childhood asthma, we
      performed a repeated-measures analysis of methacholine PC(20) data from the
      Childhood Asthma Management Program, a 4-year, multicenter, randomized, double
      masked, placebo-controlled trial of 1041 children age 5 to 12 years comparing the
      long-term efficacy of ICS with mast cell stabilizing agents or placebo. RESULTS:
      Although improvement was seen in both groups, children with asthma and IUS
      exposure had on average 26% less of an improvement in airway responsiveness over
      time compared with unexposed children (P = .01). Moreover, while children who
      were not exposed to IUS who received budesonide experienced substantial
      improvement in PC(20) compared with untreated children (1.25-fold increase; 95%
      CI, 1.03-1.50; P = .02), the beneficial effects of budesonide were attenuated
      among children with a history of IUS exposure (1.04-fold increase, 95% CI, 0.65
      1.68; P = .88). CONCLUSION: In utero smoke exposure reduces age-related
      improvements in airway responsiveness among children with asthma. Moreover, IUS
      appears to blunt the beneficial effects of ICS use on airways responsiveness.
      These results emphasize the importance of preventing this exposure through
      smoking cessation counseling efforts with pregnant women.

PMID- 20673989
TI  - MiR-155 is overexpressed in patients with atopic dermatitis and modulates T-cell
      proliferative responses by targeting cytotoxic T lymphocyte-associated antigen 4.
AB  - BACKGROUND: MicroRNAs (miRNAs) are short noncoding RNAs that suppress gene
      expression at the posttranscriptional level. Atopic dermatitis is a common
      chronic inflammatory skin disease characterized by the presence of activated T
      cells within the skin. OBJECTIVE: We sought to explore the role of miRNAs in the
      pathogenesis of atopic dermatitis. METHODS: Global miRNA expression in healthy
      and lesional skin of patients with atopic dermatitis was compared by using TaqMan
      MicroRNA Low Density Arrays. miR-155 expression in tissues and cells was
      quantified by means of quantitative real-time PCR. The cellular localization of
      miR-155 was analyzed by means of in situ hybridization. The regulation of
      cytotoxic T lymphocyte-associated antigen (CTLA-4) by miR-155 was investigated by
      using luciferase reporter assays and flow cytometry. CTLA-4 expression and
      functional assays were performed on T(H) cells overexpressing miR-155. RESULTS:
      miR-155 was one of the highest-ranked upregulated miRNAs in patients with atopic
      dermatitis. In the skin miR-155 was predominantly expressed in infiltrating
      immune cells. miR-155 was upregulated during T-cell differentiation/activation
      and was markedly induced by T-cell activators in PBMCs in vitro and by
      superantigens and allergens in the skin in vivo. CTLA-4, an important negative
      regulator of T-cell activation, was identified as a direct target of miR-155.
      Overexpression of miR-155 in T(H) cells resulted in decreased CTLA-4 levels
      accompanied by an increased proliferative response. CONCLUSION: miR-155 is
      significantly overexpressed in patients with atopic dermatitis and might
      contribute to chronic skin inflammation by increasing the proliferative response
      of T(H) cells through the downregulation of CTLA-4.

PMID- 20673991
TI  - Identification of sperm subpopulations with defined motility characteristics in
      ejaculates from Florida goats.
AB  - The aims of this study were to test the presence of discrete sperm subpopulations
      in Florida goat ejaculates using a computer-assisted sperm analysis (CASA) system
      and to establish the relationship between the distribution of the subpopulations
      found and individual buck, total motility, and sperm concentration. Clustering
      methods and discriminant analysis were applied to identify motile sperm
      subpopulations within the semen samples. Principal component analysis revealed
      that three principal components represented more than the 88% of the variance.
      After the cluster analysis was performed four motile sperm subpopulations were
      identified. Subpopulation 1 consisted of rapid and linear sperm (39.84%),
      Subpopulation 2 consisted of slow but linear spermatozoa (33.23%), Subpopulation
      3 consisted of rapid, high ALH but non-linear spermatozoa (14.63%), and
      Subpopulation 4 consisted of slow and non-linear spermatozoa (12.31%). There were
      significant differences in the distribution of the four subpopulations (P <
      0.001) as well as in the percentage of total motility and the overall sperm
      concentration (P < 0.05) in fresh ejaculates among the four bucks tested. In
      conclusion, four well-defined motile sperm subpopulations were identified in
      Florida goat ejaculates. The relationship between the distribution of the sperm
      subpopulations and individual buck, total motility, and sperm concentration shows
      that the spermatozoa of each have different motility patterns. Therefore, the
      study of discrete subpopulations of motile spermatozoa could lead to a
      substantial increase in information acquired during caprine semen analysis.

PMID- 20673990
TI  - A large intergenic noncoding RNA induced by p53 mediates global gene repression
      in the p53 response.
AB  - Recently, more than 1000 large intergenic noncoding RNAs (lincRNAs) have been
      reported. These RNAs are evolutionarily conserved in mammalian genomes and thus
      presumably function in diverse biological processes. Here, we report the
      identification of lincRNAs that are regulated by p53. One of these lincRNAs
      (lincRNA-p21) serves as a repressor in p53-dependent transcriptional responses.
      Inhibition of lincRNA-p21 affects the expression of hundreds of gene targets
      enriched for genes normally repressed by p53. The observed transcriptional
      repression by lincRNA-p21 is mediated through the physical association with hnRNP
      K. This interaction is required for proper genomic localization of hnRNP-K at
      repressed genes and regulation of p53 mediates apoptosis. We propose a model
      whereby transcription factors activate lincRNAs that serve as key repressors by
      physically associating with repressive complexes and modulate their localization
      to sets of previously active genes.

PMID- 20673992
TI  - Durability of four composite resin cements bonded to dentin under simulated
      pulpal pressure.
AB  - OBJECTIVES: This study aimed to investigate the durability of four adhesive
      luting systems bonded to dentin with and without simulated hydrostatic pulpal
      pressure (PP). METHODS: Composite blocks were bonded to dentin with four adhesive
      systems: Multilink Automix (MA), Multilink Sprint (MS), Clearfil Esthetic cement
      (CE) and RelyX ARC (RAC) under either a PP of 0 or 15 cm H(2)O. After 3 d water
      storage at 37 degrees C or thermal cycling (TC), of 30 d with 5000 TC or 90 d
      with 15,000 TC micro-tensile bond strength (microTBS) was tested. Failure
      analysis of the bonding interface was performed using a scanning electron
      microscope (SEM). RESULTS: Independent of PP application groups MA and RAC showed
      significantly higher microTBS than CE and MS (P< or =0.05). A significant
      decrease in microTBS was found for RAC and MS when subjected to PP (P< or =0.05),
      whereas CE and MA showed no significant difference (P>0.05). TC had no
      significant influence on the microTBS in RAC, MA and CE without PP application
      (P>0.05), whereas CE with PP and MS showed a significant decrease in microTBS (P<
      or =0.05) when subjected to TC. SIGNIFICANCE: Based on these results, there were
      significant differences between materials. Pulpal pressure and artificial aging
      also seem to have an effect on in-vitro evaluation of bonding durability. If
      considered relevant to the materials' service performance then these conditions
      should be applied in the materials' testing.

PMID- 20673993
TI  - National identification of Dutch youth: an exploratory study.
AB  - 246 Dutch participants aged 8, 10, 12, 14, and 16 years were presented with the
      Strength of Identification Scale (SoIS; Barrett, 2007) and the National Identity
      scale based on Cultural and Historical achievements (NICH; derived from the
      NATID, Keillor & Hult, 1999). The study aimed to examine the extent and nature of
      Dutch children and adolescents' identification with The Netherlands and to
      explore whether changes in aspects of national identification are evident across
      age. Already at age 8 years children identify themselves with the Dutch nation
      and with increasing age national identification becomes primarily determined by
      the extent that participants consider themselves to be Dutch and show positive
      affect towards the Dutch nation. Identification on the basis of cultural and
      historical achievements of the Dutch people became less evident following the age
      of 10 years although Dutch historical and cultural achievements contributed
      significantly to the extent of national identification.

PMID- 20673994
TI  - Cognitive behaviour therapy for adolescent offenders with mental health problems
      in custody.
AB  - Many studies have identified high levels of mental health problems among
      adolescents in custody and there is increasing evidence that mental health
      problems in this population are associated with further offending and mental
      health problems into adulthood. Despite recent improvements in mental health
      provision within custodial settings there is little evidence of structured
      interventions being offered or of their effectiveness being evaluated. A
      cognitively based intervention was developed and offered to adolescents with a
      variety of mental health problems in different secure settings, and the outcomes
      compared with a control group. Although this small-scale study did not identify
      significant differences in outcomes for the two groups, both recruitment and
      retention in therapy were good, and potential candidates were not excluded on the
      basis of learning difficulties or co-morbidity. The study demonstrated the
      viability of a delivering cognitively based intervention for common mental health
      problems within secure settings.

PMID- 20673996
TI  - Is cardiometabolic risk improved by weight-loss drugs?

PMID- 20673995
TI  - Effect of naltrexone plus bupropion on weight loss in overweight and obese adults
      (COR-I): a multicentre, randomised, double-blind, placebo-controlled, phase 3
      trial.
AB  - BACKGROUND: Despite increasing public health concerns regarding obesity, few safe
      and effective drug treatments are available. Combination treatment with sustained
      release naltrexone and bupropion was developed to produce complementary actions
      in CNS pathways regulating bodyweight. The Contrave Obesity Research I (COR-I)
      study assessed the effect of such treatment on bodyweight in overweight and obese
      participants. METHODS: Men and women aged 18-65 years who had a body-mass index
      (BMI) of 30-45 kg/m(2) and uncomplicated obesity or BMI 27-45 kg/m(2) with
      dyslipidaemia or hypertension were eligible for enrolment in this randomised,
      double-blind, placebo-controlled, phase 3 trial undertaken at 34 sites in the
      USA. Participants were prescribed mild hypocaloric diet and exercise and were
      randomly assigned in a 1:1:1 ratio to receive sustained-release naltrexone 32 mg
      per day plus sustained-release bupropion 360 mg per day combined in fixed-dose
      tablets (also known as NB32), sustained-release naltrexone 16 mg per day plus
      sustained-release bupropion 360 mg per day combined in fixed-dose tablets (also
      known as NB16), or matching placebo twice a day, given orally for 56 weeks. The
      trial included a 3-week dose escalation. Randomisation was done by use of a
      centralised, computer-generated, web-based system and was stratified by study
      centre. Co-primary efficacy endpoints at 56 weeks were percentage change in
      bodyweight and proportion of participants who achieved a decrease in bodyweight
      of 5% or more. The primary analysis included all randomised participants with a
      baseline weight measurement and a post-baseline weight measurement while on study
      drug (last observation carried forward). This study is registered with
      ClinicalTrials.gov, number NCT00532779. FINDINGS: 1742 participants were enrolled
      and randomised to double-blind treatment (naltrexone 32 mg plus bupropion, n=583;
      naltrexone 16 mg plus bupropion, n=578; placebo, n=581). 870 (50%) participants
      completed 56 weeks of treatment (n=296; n=284; n=290, respectively) and 1453
      (83%) were included in the primary analysis (n=471; n=471; n=511). Mean change in
      bodyweight was -1.3% (SE 0.3) in the placebo group, -6.1% (0.3) in the naltrexone
      32 mg plus bupropion group (p<0.0001 vs placebo) and -5.0% (0.3) in the
      naltrexone 16 mg plus bupropion group (p<0.0001 vs placebo). 84 (16%)
      participants assigned to placebo had a decrease in bodyweight of 5% or more
      compared with 226 (48%) assigned to naltrexone 32 mg plus bupropion (p<0.0001 vs
      placebo) and 186 (39%) assigned to naltrexone 16 mg plus bupropion (p<0.0001 vs
      placebo). The most frequent adverse event in participants assigned to combination
      treatment was nausea (naltrexone 32 mg plus bupropion, 171 participants [29.8%];
      naltrexone 16 mg plus bupropion, 155 [27.2%]; placebo, 30 [5.3%]). Headache,
      constipation, dizziness, vomiting, and dry mouth were also more frequent in the
      naltrexone plus bupropion groups than in the placebo group. A transient increase
      of around 1.5 mm Hg in mean systolic and diastolic blood pressure was followed by
      a reduction of around 1 mm Hg below baseline in the naltrexone plus bupropion
      groups. Combination treatment was not associated with increased depression or
      suicidality events compared with placebo. INTERPRETATION: A sustained-release
      combination of naltrexone plus bupropion could be a useful therapeutic option for
      treatment of obesity. FUNDING: Orexigen Therapeutics.

PMID- 20673997
TI  - Porous nanofibrous PLLA scaffolds for vascular tissue engineering.
AB  - Tissue-engineered small-diameter vascular grafts are needed for patients
      requiring replacement of their injured coronary and below-the-knee vessels.
      Understanding the interactions between the scaffolds and implanted cells and
      therefore the phenotype control of smooth muscle cells (SMCs) is critical for
      constructing functional vascular grafts. In this study, the effect of nanofibrous
      (NF) poly-L-lactide (PLLA) scaffolds on phenotype control of human aortic smooth
      muscle cells (HASMCs) was investigated. A tubular NF PLLA scaffold for blood
      vessel regeneration was fabricated and cell seeding studies showed cell
      distribution throughout the scaffold. It was found that NF PLLA scaffolds
      preferentially supported contractile phenotype of HASMCs under the in vitro
      culture conditions, as evidenced by elevated gene expression level of SMCs
      contractile markers including smooth muscle myosin heavy chain, smoothelin and
      myocardin. In vivo subcutaneous implantation studies confirmed HASMCs
      differentiation in the implants. Taken together, the results showed promising
      application of the porous NF PLLA scaffolds for reconstruction of tissue
      engineered vascular grafts.

PMID- 20673998
TI  - The influence of collagen film nanostructure on pulmonary stem cells and collagen
      stromal cell interactions.
AB  - We have recently identified a rare subpopulation of lung colony cells with the
      characteristics of pulmonary stem cells, and discovered that stem cell colonies
      grew preferentially on type I collagen films in a serum-free medium. In order to
      further optimize culture conditions and determine stem cell growth in relation to
      microenvironments (including the stroma, medium and nanostructures of type I
      collagen films), both primary and pre-sorted stem cells were cultured on the type
      I collagen films with controllable degree of polymerization and film thickness,
      as confirmed by an atomic force microscope and surface profiler. We found that in
      a primary culture, the spreading of stromal cells is greatly restrained and both
      the size and number of colonies are significantly reduced on highly polymerized
      collagen films. In contrast, in a pre-sorted stem cell culture without stromal
      cells, the intrinsic stem cell properties and cell number are independent of the
      degree of collagen polymerization. Our results indicate that the nanostructures
      of type I collagen films primarily affect stem colony formation through the
      collagen-stroma interactions. In those cases, collagen film thickness shows no
      effect on colony formation.

PMID- 20673999
TI  - The role of reactive oxygen species and hemeoxygenase-1 expression in the
      cytotoxicity, cell cycle alteration and apoptosis of dental pulp cells induced by
      BisGMA.
AB  - Biocompatibility of dentin bonding agents (DBAs) and resin composite is important
      to preserve the pulp vitality after operative restoration. Bisphenol-glycidyl
      methacrylate (BisGMA) is one common monomer adding into DBAs and resin. In this
      study, we found that exposure of human dental pulp cells to BisGMA (>0.1 mM) led
      to cytotoxicity, G2/M cell cycle arrest and apoptosis as analyzed by propidium
      iodide (PI) and PI/annexin V dual fluorescent flow cytometry. These events were
      associated with a decline of cdc2, cdc25C and cyclinB1 expression at both mRNA
      and protein levels. BisGMA also induced the expression of hemeoxygenase-1 (HO-1),
      an oxidative stress responsive gene, in pulp cells. Catalase could prevent the
      BisGMA-induced alteration of cell cycle-related genes (cdc2, cdc25C, cyclinB1)
      and HO-1 expression in dental pulp cells. Interestingly, Zn-protoporphyrin (2.5-5
      microM), a HO inhibitor, enhanced the BisGMA-induced reactive oxygen species
      (ROS) production and cytotoxicity. These results suggest that exposure to higher
      concentrations of BisGMA may stimulate ROS production, cell cycle arrest,
      apoptosis and cell death. Inducing the expression of HO-1 in dental pulp cells by
      BisGMA is mediated by ROS production and important to protect dental pulp against
      the toxicity by monomers present in composite resin and DBAs.

PMID- 20674000
TI  - The expansion of human ES and iPS cells on porous membranes and proliferating
      human adipose-derived feeder cells.
AB  - For clinical application of human embryonic stem cells (hESCs), it is critical to
      develop hESC culture techniques that completely exclude the use of animal feeder
      cells, mitotic inhibition, and enzyme treatments used in conventional hESC
      culture systems. Toward this goal, we attempted to maintain hESCs and induced
      pluripotent stem (iPS) cells on porous membranes (PMs) with proliferative human
      adipose-derived stromal cells (ASCs) seeded on the bottom surface of inverted
      PMs. This culture condition will ensure that the two cell types are separate from
      each other, yet retain the ability to interact through the pores of the membrane.
      We found that hESCs and iPS cells can be maintained stably and mechanically
      transferred without the need for enzyme treatment. In addition, the pluripotency
      of hESCs and iPS cells was stably maintained, as evidenced by immunostaining of
      Oct4, SSEA3/4 and TRA-1-60 as well as RT-PCR analyses of Nanog, Oct4 and Sox2
      expression. Furthermore, hESCs cultured on PMs showed a normal karyotype and in
      vivo teratoma formation containing all three germ layers.

PMID- 20674001
TI  - The relationship between terminal functionalization and molecular weight of a
      gene delivery polymer and transfection efficacy in mammary epithelial 2-D
      cultures and 3-D organotypic cultures.
AB  - Non-viral gene delivery vectors were developed for efficient gene transfer to
      hard-to-transfect mouse mammary epithelial cells. Ten modified versions of the
      same base poly(beta-amino ester), poly(1,4-butanediol diacrylate-co-5-amino-1
      pentanol), were tested in both traditional 2-D monolayer and in 3-D organotypic
      cultures. The polymers self-assembled with plasmid DNA encoding enhanced green
      fluorescent protein to form nanoparticles (approximately 100 nm) used to
      transfect the cells. Nanoparticle transfection efficacy was tuned by changes in
      synthesis and fabrication conditions and the transfection efficacy was analyzed
      using confocal microscopy and flow cytometry. The best performing polymeric
      nanoparticles transfected 57 +/- 6% of the cells in 2-D culture and 6 +/- 1% of
      the cells in 3-D culture. Small modifications to the polymer end-capping
      molecules and tuning of polymer molecular weight could either significantly
      enhance the transfection efficacy up to 6-fold or instead abolish efficacy
      completely. The efficacy of leading polymers was higher than that of the
      commercial transfection agent FuGENE HD by a factor of 13 in 2-D and 2 in 3-D.
      These non-viral nanoparticles may be useful as delivery reagents or targeted
      therapeutics for breast cancer. This gene delivery strategy is also a promising
      approach for studying the normal development of the mammary gland.

PMID- 20674002
TI  - Plastic compressed collagen as a biomimetic substrate for human limbal epithelial
      cell culture.
AB  - We describe, for the first time, the use of cellular plastic compressed collagen
      as a substrate for human limbal epithelial cell expansion and stratification. The
      characteristics of expanded limbal epithelial cells on either acellular collagen
      constructs or those containing human limbal fibroblasts were compared to a human
      central cornea control. After compression, human fibroblasts in collagen
      constructs remained viable and limbal epithelial cells were successfully expanded
      on the surface. After airlifting, a multilayered epithelium formed with
      epithelial cell morphology very similar to that of cells in the central cornea.
      Immunochemical staining revealed expression of basement membrane proteins and
      differentiated epithelial cell markers found in native central cornea.
      Ultrastructural analysis revealed cells on collagen constructs had many features
      similar to central cornea, including polygonal, tightly opposed surface
      epithelial cells with microvilli and numerous desmosomes at cell-cell junctions.
      Taken together, these data demonstrate that plastic compressed collagen
      constructs can form the basis of a biomimetic tissue model for in vitro testing
      and could potentially provide a suitable alternative to amniotic membrane as a
      substrate for limbal epithelial cell transplantation.

PMID- 20674003
TI  - Activation of mitogen-activated protein kinases cellular signal transduction
      pathway in mammalian cells induced by silicon carbide nanowires.
AB  - Because of emerging biomedical applications of nanoscale materials, the behavior
      of cells in contact with nanoscale materials must be better understood. SiC
      nanostructures constitute a new class of biomaterials and have potential in many
      applications. In this study, the cellular signal transduction processes and
      toxicity mechanisms of silicon carbide nanowires (SiCNWs) are investigated. The
      Chinese hamster ovary (CHO) cells in contact with SiCNWs have significantly lower
      reproduction rates and genomic instability which may be the upstream event of
      cell apoptosis. Expression of the phosphorylated form of the mitogen-activated
      protein kinases (MAPKs) family including phosphorylated signal-regulated kinases
      (p-ERKs), phosphorylated c-Jun NH2-terminal kinases (p-JNKs), and phosphorylated
      p38-mitogen-activated protein kinases (p-p38) are observed at different time
      points during exposure to SiCNWs. Moreover, activation of the MAPKs family by
      phosphorylation which is an upstream event giving rise to expression of
      cyclooxygenase-2 (COX-2) is also observed. The specific inhibitors of the MAPKs
      family are found to restrain COX-2 high expression at some time points. Our
      results show that activation of the MAPKs cellular signaling pathway and over
      expression of COX-2 are the main toxicity mechanisms in SiCNWs irritation.

PMID- 20674004
TI  - Patterning network structure to spatially control cellular remodeling and stem
      cell fate within 3-dimensional hydrogels.
AB  - The spatially directed 3-dimensional (3D) remodeling of synthetic materials may
      be useful to regionally control cell behavior. In this work, we developed a
      process to synthesize hyaluronic acid hydrogels using multiple modes of
      crosslinking applied sequentially; a primary addition reaction to introduce
      protease degradable peptide crosslinks, then a UV light-induced secondary radical
      reaction (enabling spatial control) to introduce non-degradable kinetic chains.
      These differential network structures either permitted (primary crosslinking
      only, "-UV") or inhibited (sequential crosslinking, "+UV") cellular remodeling.
      This behavior was validated by controlling the outgrowth from chick aortic arches
      or the spreading of encapsulated mesenchymal stem cells (MSCs), where only -UV
      regions permitted arch outgrowth and MSC spreading. Additionally, network
      structures dictated adipogenic/osteogenic MSC fate decisions, with spatial
      control, by controlling encapsulated MSC spreading. This manipulation of
      microenvironmental cues may be valuable for advanced tissue engineering
      applications requiring the spatial control of cells in 3D.

PMID- 20674006
TI  - Anti-angiogenic activity of heparin-like polysulfonated polymeric drugs in 3D
      human cell culture.
AB  - The activity of new anti-angiogenic polymeric drugs was tested in a 3D
      endothelial cell culture system applied as a model of angiogenesis. The assay was
      performed in a highly reproducible fibrin matrix that supported endothelial cell
      attachment, proliferation, migration, and formation of capillary-like structures.
      Active growth factors (FGF and/or VEGF) were added to the medium to induce the
      formation of blood vessel-like structures, and the effect of the active polymers
      was then tested by a semi-quantitative immunostaining protocol and visualized by
      laser-scanning confocal microscopy. The synthetic heparin-like macromolecules
      that were tested for their anti-angiogenic efficacy were previously characterized
      in terms of their anti-proliferative activity in 2D tissue culture. Two different
      anti-angiogenic monomers, a methacrylic derivative of 5-amino-2
      naphthalenesulfonic acid (MANSA) and 2-acrylamido-2-methylpropane sulfonic acid
      (AMPS), were copolymerized with a hydrophilic monomer (vinyl pyrrolidone, VP) or
      a hydrophobic monomer (butyl acrylate, BA), giving rise to different copolymeric
      systems with controlled microstructure and supramolecular organization. Both
      copolymeric systems have demonstrated a composition-dependent anti-mitogenic
      effect in "2D in vitro" cell culture experiments using aFGF as pro-angiogenic
      growth factor and BALB/c 3T3 fibroblast as cell model, as was shown in a previous
      publication. These 3D experiments provide evidence for the strong and specific
      modulation of angiogenesis by these systems. The 3D experiments constitute an
      improvement over 2D in vitro experiments and in vivo experiments with angiogenic
      drugs and may help to reduce the number of animal experiments.

PMID- 20674005
TI  - Use of molecular beacons to image effects of titanium surface microstructure on
      beta1 integrin expression in live osteoblast-like cells.
AB  - This study used molecular beacon technology to examine substrate-dependent
      changes in integrin subunit expression in living cells. Molecular beacons are
      oligonucleotide probes that can be delivered into live cells to allow for real
      time imaging of mRNA. They have a stem-loop hairpin structure with a fluorophore
      quencher pair, which opens when bound to the target mRNA sequence, resulting in a
      fluorescent signal upon excitation. A novel molecular beacon that is specific to
      the beta1 integrin subunit mRNA was developed and used to image osteoblast-like
      MG63 cells in vitro on both glass and titanium surfaces of varying roughness.
      Specificity was verified by comparing the molecular beacon signal intensities to
      real-time PCR results in both wild-type cells and cells with shRNA knockdown of
      beta1 integrin mRNA. The molecular beacon was able to detect changes due to both
      surface microtopography and silencing of the mRNA target. The results showed that
      effects of the substrate on beta1 mRNA noted previously in confluent cultures
      were evident in pre-confluent cells as well, supporting the hypothesis that beta1
      integrin pairs are important in proliferation as well as differentiation of
      osteoblasts. This technique overcomes the limitations of traditional gene assays
      (PCR, immunofluorescence) by allowing for the real-time measurement and tracking
      of specific mRNAs in individual live cells prior to confluence.

PMID- 20674007
TI  - Primary cardiomyocyte-targeted bioreducible polymer for efficient gene delivery
      to the myocardium.
AB  - A cardiomyocyte-targeted Fas siRNA delivery system was developed using primary
      cardiomyocyte (PCM) specific peptide-modified polymers with high transfection
      efficiency and low cytotoxicity. Primary cardiomyocyte (PCM) specific peptide,
      selected by phage display, was conjugated to bioreducible poly(cystamine
      bisacrylamide-diaminohexane, CBA-DAH) (PCD). The specificity of the PCM-modified
      polymer to cardiomyocytes was confirmed by competition study with free PCM ligand
      and by delivery to non-cardiomyocyte NIH 3T3 fibroblasts. The cellular binding
      and uptake of the PCM-polymer/pDNA polyplex was inhibited by addition of free PCM
      peptide. The impact of PCM conjugation on cellular uptake and transfection
      efficiency was greater in H9C2 rat cardiomyocytes than in NIH 3T3 cells. Fas
      siRNA/PCM-polymer polyplexes exhibited significant Fas gene silencing in rat
      cardiomyocytes under hypoxic conditions, leading to inhibition of cardiomyocyte
      apoptosis. These findings demonstrate the utility of the addition of a primary
      cardiomyocyte (PCM) specific peptide modification to a bioreducible polymer for
      targeted delivery of Fas siRNA to inhibit cardiomyocyte apoptosis.

PMID- 20674008
TI  - Sequential delivery of vascular endothelial growth factor and sphingosine 1
      phosphate for angiogenesis.
AB  - Angiogenesis is an organized series of events, beginning with vessel
      destabilization, followed by endothelial cell re-organization, and ending with
      vessel maturation. Vascular endothelial growth factor (VEGF) aids in vascular
      permeability and endothelial cell recruitment while sphingosine 1-phosphate (S1P)
      stimulates vascular stability. Accordingly, VEGF may inhibit vessel stabilization
      while S1P may inhibit endothelial cell recruitment. For this reason, we created a
      new externally-regulated delivery model that not only permits sustained release
      of bioactive factors, but also temporal separation of the delivery of growth
      factors. Using this model, sequential delivery of factors was first confirmed in
      vitro with associated endothelial cells responding in a dose dependent manner.
      Furthermore, using a modified murine Matrigel plug model, it is apparent that
      delivery strategies where VEGF presentation is temporally separated from S1P
      presentation not only led to greater recruitment of endothelial cells, but also
      higher maturation index of associated vessels.

PMID- 20674009
TI  - An anti-ROS/hepatic fibrosis drug delivery system based on salvianolic acid B
      loaded mesoporous silica nanoparticles.
AB  - The rhodamine B (RhB) covalently grafted SBA-15-structured mesoporous silica
      nanoparticles (MSNs-RhB) of high surface area (750 m(2) g(-1)), large pore volume
      (0.7 cm(3) g(-1)), uniform particle size (about 400 nm) and positively charged
      surface (29.6 +/- 5.0 mV), has been developed as a drug delivery system (SAB@MSNs
      RhB) for anti-ROS (reactive oxygen species)/hepatic fibrosis by loading a
      negatively charged drug salvianolic acid B (SAB). The dosage formulation SAB@MSNs
      RhB effectively protected the loaded drug SAB from decomposition. The multi
      release experimental results showed that SAB@MSNs-RhB exhibited an outstanding
      SAB sustained-release property, and relatively high SAB release rates and
      concentrations in a long term after the consumption of previously released SAB as
      compared to SAB loaded MSNs (SAB@MSNs) of negatively charged surface (-31.1 +/-
      2.6 mV). The influences of the drug concentration, incubation time, drug formula
      and drug carrier on the ROS level, proliferative activity and cytotoxicity of LX
      2 cells were evaluated. The results showed that the inhibiting effect of SAB@MSNs
      RhB on the ROS level and proliferative activity of LX-2 cells was more remarkable
      than free SAB in a long term (72 h), and became more intensive with the increase
      of the sample concentration and the incubation time. SAB@MSNs-RhB enhanced the
      cellular drug uptake, the drug bioaccessability and efficacy for anti-ROS/hepatic
      fibrosis via the nanoparticles-mediated endocytosis and the sustained release of
      the drug. There was no visible cytotoxicity of free SAB, MSNs-RhB and SAB@MSNs
      RhB against LX-2 cells in a broad concentration range (0.5-100 microm) and
      incubation time periods up to 72 h. The blood compatibility of the carrier MSNs
      RhB was evaluated by investigating the hemolysis and coagulation behaviors in a
      broad concentration range (50-500 microg mL(-1)) under in vitro conditions. The
      results suggested that MSNs-RhB possessed good blood compatibility.

PMID- 20674010
TI  - The influence of skeletal maturity on allogenic synovial mesenchymal stem cell
      based repair of cartilage in a large animal model.
AB  - One of the potential factors that may affect the results of mesenchymal stem cell
      (MSC)-based therapy is the age of donors and recipients. However, there have been
      no controlled studies to investigate the influence of skeletal maturity on the
      MSC-based repair of cartilage. The purpose of this study was to compare the
      repair quality of damaged articular cartilage treated by a scaffold-free three
      dimensional tissue-engineered construct (TEC) derived from synovial MSCs between
      immature and mature pigs. Synovial MSCs were isolated from immature and mature
      pigs and the proliferation and chondrogenic differentiation capacities were
      compared. The TEC derived from the synovial MSCs were then implanted into
      equivalent chondral defects in the medial femoral condyle of both immature and
      mature pigs, respectively. The implanted defects were morphologically and
      biomechanically evaluated at 6 months postoperatively. There was no skeletal
      maturity-dependent difference in proliferation or chondrogenic differentiation
      capacity of the porcine synovial MSCs. The TEC derived from synovial MSCs
      promoted the repair of chondral lesion in both immature and mature pigs without
      the evidence of immune reaction. The repaired tissue by the TEC also exhibited
      similar viscoelastic properties to normal cartilage regardless of the skeletal
      maturity. The results of the present study not only suggest the feasibility of
      allogenic MSC-based cartilage repair over generations but also may validate the
      use of immature porcine model as clinically relevant to test the feasibility of
      synovial MSC-based therapies in chondral lesions.

PMID- 20674011
TI  - Differential efficacy of gels derived from small intestinal submucosa as an
      injectable biomaterial for myocardial infarct repair.
AB  - Injectable biomaterials have been recently investigated as a therapeutic approach
      for cardiac repair. Porcine-derived small intestinal submucosa (SIS) material is
      currently used in the clinic to promote accelerated wound healing for a variety
      of disorders. In this study, we hypothesized that gels derived from SIS
      extracellular matrix would be advantageous as an injectable material for cardiac
      repair. We evaluated 2 forms of SIS gel, types B (SIS-B) and C (SIS-C), for their
      ability to provide a therapeutic effect when injected directly into ischemic
      myocardium using a murine model of an acute myocardial infarction.
      Echocardiography analysis at both 2 and 6 weeks after infarction demonstrated
      preservation of end-systolic left ventricular geometry and improvement of cardiac
      contractility in the hearts injected with SIS-B when compared with control hearts
      injected with saline. However, the SIS-C gel provided no functional efficacy in
      comparison with control. Histological analysis revealed that SIS-B reduced
      infarct size and induced angiogenesis relative to control, whereas injection of
      SIS-C had minimal effect on these histological parameters. Characterization of
      both gels revealed differential growth factor content with SIS-B exhibiting
      higher levels of basic fibroblast growth factor than SIS-C, which may explain, at
      least in part, the differential histological and functional results. This study
      suggests that SIS gel offers therapeutic potential as an injectable material for
      the repair of ischemic myocardium. Further understanding of SIS gel
      characteristics, such as biological and physical properties, that are critical
      determinants of efficacy would be important for optimization of this biomaterial
      for cardiac repair.

PMID- 20674012
TI  - Effects of immobilizing sites of RGD peptides in amphiphilic block copolymers on
      efficacy of cell adhesion.
AB  - This paper examines the effects of immobilizing sites of a bioactive ligand on
      its biological efficacy in a self assembly biomaterial. We synthesized an
      amphiphilic block copolymer PCLA-PEG-PCLA (PCLA: poly(epsilon-caprolactone-co
      lactide), PEG: poly(ethylene glycol)), and then achieved immobilization of
      arginine-glycine-aspartate (RGD) peptides into either hydrophobic PCLA blocks or
      hydrophilic PEG blocks. The block copolymers could self assemble into hydrogels
      composed of percolated micelle network in water, and the sol-gel transition
      temperature was adjusted between room and body temperatures. In vitro
      examinations of chondrocyte viability were performed. We found that
      immobilization of RGD in hydrophilic blocks enhanced cell adhesion on the
      corresponding hydrogel surface much more significantly than that in hydrophobic
      blocks. The difference might come from that RGD ligands in hydrophilic blocks are
      exposed on the micellar surface in water more than those in hydrophobic blocks.
      The present research highlights the importance of the immobilizing sites of RGD
      peptides in amphiphilic polymers on the eventual cell-binding efficacy, and is
      thus meaningful for guiding the molecular design of bioactive materials.

PMID- 20674013
TI  - Vascular endothelial growth factor (VEGF) and VEGF-receptor expression in
      placenta of hyperglycemic pregnant women.
AB  - Hyperglycemia occurs in a variety of conditions such as overt diabetes,
      gestational diabetes and mild hyperglycemia, all of which are generally defined
      based on the oral glucose tolerance test and glucose profiles. Whereas diabetes
      has received considerable attention in recent decades, few studies have examined
      the mechanisms of mild hyperglycemia and its associated disturbances. Mild
      gestational hyperglycemia is associated with macrosomia and a high risk of
      perinatal mortality. Morphologically, the placenta of these women is
      characterized by an increase in the number of terminal villi and capillaries,
      presumably as part of a compensatory mechanism to maintain homeostasis at the
      maternal-fetal interface. In this study, we analised the expression of VEGF and
      its receptors VEGFR-1 (Flt-1) and VEGFR-2 (KDR) in placentas from mildly
      hyperglycemic women. This expression was compared with that of normoglycemic
      women and women with gestational and overt diabetes. Immunohistochemistry
      revealed strong staining for VEGF and VEGFR-2 in vascular and trophoblastic cells
      of mildly hyperglycemic women, whereas the staining for VEGFR-1 was discrete and
      limited to the trophoblast. The pattern of VEGF and VEGF-receptor reactivity in
      placentas from women with overt diabetes was similar to that of normoglycemic
      women. In women with gestational diabetes, strong staining for VEGFR-1 was
      observed in vascular and trophoblastic cells whereas VEGF and VEGFR-2 were
      detected only in the trophoblast. The expression of these proteins was confirmed
      by western blotting, which revealed the presence of an additional band of 75 kDa.
      In the decidual compartment, only extravillous trophoblast reacted with all
      antibodies. Morphological analysis revealed collagen deposition around large
      arteries in all groups with altered glycemia. These findings indicate a placental
      response to altered glycemia that could have important consequences for the
      fetus. The change in the placental VEGF/VEGFR expression ratio in mild
      hyperglycemia may favor angiogenesis in placental tissue and could explain the
      hypercapillarization of villi seen in this gestational disturbance.

PMID- 20674015
TI  - Therapy-related myelodysplastic syndrome with 17p deletion following long-term
      azathioprine treatment.

PMID- 20674014
TI  - Functional distinctions in cytosolic calcium regulation between cells of the
      glomerular filtration barrier.
AB  - The importance of intracellular calcium ([Ca(2+)]i) regulation in the glomerular
      filtration barrier (GFB) has recently been highlighted by mutations in the cation
      channel TRPC6, resulting in a renal-specific phenotype. We examined the effects
      of FFA, a tool that can activate TRPC6, on [Ca(2+)]i in human conditionally
      immortalised glomerular endothelial cells (ciGEnC) and human podocytes (ciPod)
      that form the GFB. Changes in [Ca(2+)]i stimulated by FFA were measured in Fura 2
      AM loaded cells. In GEnC, cell activation by FFA was dependent on external
      Ca(2+), yet in ciPod it was not. Depletion of internal Ca(2+) stores with
      thapsigargin did not affect cell activation by FFA in ciGEnC, but inhibited it in
      ciPod in a nephrin-dependent manner, demonstrated using nephrin deficient (ND)
      ciPod in conjunction with nephrin rescue experiments. FFA induced [Ca(2+)]i store
      release in ciPod, but not in ciGEnC or ND ciPod. In parallel, there were
      differences in the localisation of overexpressed TRPC6 between ciGEnC and ciPod.
      Furthermore, co-transfection of nephrin with TRPC6 in HEK293 cells reduced the
      FFA-induced increase in [Ca(2+)]i and nephrin clustering altered TRPC6
      distribution. In conclusion, cell activation by FFA in podocytes stimulates the
      opening of a Ca(2+) channel, probably TRPC6, in a nephrin-dependent manner with a
      different activation profile to GEnC.

PMID- 20674016
TI  - Methods for measuring proteasome activity: current limitations and future
      developments.
AB  - The proteasome has been validated as a therapeutic target, with proteasome
      inhibitors showing particular efficacy in the treatment of Multiple Myeloma. A
      wide range of methods have been developed to profile proteasome activity. These
      include the current method of choice fluorogenic peptide substrates, as well as
      bioluminescent imaging, immunological methods, and more recently, site-specific
      fluorescent probes. The aim of this review is to evaluate the currently available
      methods for profiling proteasome activity and their suitability for use in
      translational studies. Ongoing development of techniques for profiling proteasome
      activity will facilitate future research into proteasome-related pathologies,
      thus accelerating the development of more specific drug regimes.

PMID- 20674017
TI  - Should minimal residual disease monitoring be the standard of care for all
      patients with acute promyelocytic leukemia?

PMID- 20674018
TI  - NF-kappaB localization in multiple myeloma plasma cells and mesenchymal cells.
AB  - Several reports demonstrated that the activation of Nuclear Factor-kappa B NF
      kappaB is essential for the pathogenesis of multiple myeloma (MM). We analyzed
      the nuclear localization of NF-kappaB in MM-cells derived from 60 different
      patients with MM at presentation and in relapse, as well as in three myeloma cell
      lines. Nuclear localization (the active form) of NF-kappaB was detected in only
      one MM-sample from a refractory patient and in two samples from relapsed
      patients, while all the other samples, including the MM-cell lines, almost
      exclusively express the cytoplasmic (inactive) form of NF-kappaB. In mesenchymal
      cells from MM-patients NF-kappaB was clearly present in the nucleus. In addition,
      the proteasome inhibitor Bortezomib, which is described to antagonize NF-kappaB
      activity, had a consistent antitumor activity against both chemoresistant and
      chemosensitive MM-cells, regardless the NF-kappaB localization, thus suggesting
      the existence of other molecular targets of proteasome inhibitors in MM.

PMID- 20674019
TI  - The role of p53 and autophagy in Dasatinib resistance of CLL lymphocytes.

PMID- 20674020
TI  - The deacetylase inhibitor LAQ824 induces notch signalling in haematopoietic
      progenitor cells.
AB  - AML progenitor cells (AML-PC) undergo significant apoptosis in response to the
      deacetylase inhibitor (DACi) LAQ824 and lose the replating capacity which was not
      observed with the DACi valproic acid. Treatment of normal hematopoietic
      progenitor cells (HPC) with LAQ824 resulted in (i) inhibition of differentiation,
      (ii) an G2/M cell cycle arrest exclusively in multipotent CD34(+) HPC and (iii)
      induction of apoptosis predominantly in committed CD34(-) HPC. Gene expression
      analysis showed induction of coactivator and target genes of the notch pathway as
      well as cell cycle arrest-inducing genes in the most primitive CD34(+) CD38(-)
      HPC population which may in part be responsible for the considerable, but
      reversible haematotoxicity of this drug.

PMID- 20674021
TI  - Decreased incidence of febrile episodes with antibiotic prophylaxis in the
      treatment of decitabine for myelodysplastic syndrome.
AB  - We analyzed the role of antibiotic prophylaxis during decitabine treatment for
      MDS. The primary endpoint was the incidence of febrile episodes. The total number
      of decitabine cycles given to 28 patients was 131, and febrile episodes occurred
      in 15 cycles (11.5%). Antibiotic prophylaxis was orally administered in 95 cycles
      (72.5%). Febrile episodes were significantly less frequent among patients who
      received antibiotic prophylaxis (7.4%) than in those without prophylaxis (22.2%)
      (P=0.017). In conclusion, antibiotic prophylaxis reduced the incidence of febrile
      episodes in patients who received decitabine treatment for MDS, especially at
      earlier cycles and in the presence of severe cytopenia.

PMID- 20674022
TI  - Introduction of oxygenated side chain into imidazolium ionic liquids: evaluation
      of the effects at different biological organization levels.
AB  - The biological effects of a class of oxygenated imidazolium ionic liquids were
      studied in comparison with alkyl imidazolium salts (BMIM BF4 and BMIM N(CN)2).The
      cellular and subcellular effects were evaluated on rat pheochromocytoma PC12 cell
      lines, through MTT test, lactate dehydrogenase release and acetylcholinesterase
      inhibition; the eco-toxicological responses were assessed through the acute
      toxicity tests towards Daphnia magna and Vibrio fischeri. The introduction of
      ethoxy moieties in the lateral chain of imidazolium cations reduced the
      biological effects in all the tests. The acute toxicity towards D. magna was not
      affected by the number of ethoxy units, but the crustacean seemed to be sensitive
      to the type of anion; on the contrary, a further addition of ethoxy moieties
      increased the toxicity towards V. fischeri, M(OE)4MIM N(CN)2 being the most toxic
      oxygenated ionic liquid. In the cytotoxicity assays the salts with oxygenated
      cations resulted ineffective compared to BMIMs, independently from the anion and
      the number of ethoxy units in the lateral chain. In order to estimate the
      influence on membrane fluidity, an analysis of fluorescence anisotropy was done
      and it indicated that BMIM BF4, the most toxic ionic liquid among the tested
      ones, led to a destabilization of the model membranes at any molarity.

PMID- 20674023
TI  - Characterization of genes expressed in response to cadmium exposure in the
      earthworm Eisenia fetida using DDRT-PCR.
AB  - The transition metal cadmium is a pervasive and persistent environmental
      contaminant that is both a human toxicant and a carcinogen. To inhibit cadmium
      induced damage, cells increase the expression of genes encoding stress-response
      proteins. The transcription of many stress-responsive genes, including those that
      encode metallothioneins, glutathione-S-transferases (GSTs) and heat shock
      proteins have been reported. The aim of this work was to investigate in Eisenia
      fetida the genes whose expressions are regulated following exposure to cadmium.
      mRNA differential display reverse transcription-polymerase chain reaction was
      used to analyze gene expression in E. fetida exposed to 50mg/l cadmium solution.
      Among the derived cDNA clones sequenced, we found 15 genes up-regulated and 12
      down-regulated in response to cadmium exposure. The translated amino acid
      sequences of eight clones were similar to the Lumbricus terrestris hemoglobin
      dodecamer, Tribolium castaneum membrane protein, Escherichia coli UMN026 DNA
      binding transcriptional activator, Brugia malayi immunoglobulin, Homo sapiens
      cell growth-inhibiting protein, Apis mellifera poly U binding factor, Escherichia
      fergusonii copper transporter, and the mRNA that encodes E. coli K-12 cytoplasmic
      insertase into membrane protein. Five cDNA fragments presented no homology with
      known gene sequences, suggesting that these sequences may either encode proteins
      not yet identified or correspond to untranslated regions of mRNA molecules. In
      depth functional analyses of these genes are needed to reveal their exact roles.

PMID- 20674024
TI  - In situ cage experiments with Potamopyrgus antipodarum--a novel tool for real
      life exposure assessment in freshwater ecosystems.
AB  - In situ experiments are an important tool within ecotoxicological research but
      there is a lack of suitable methodologies especially for freshwater invertebrate
      species. Within this study, a novel in situ methodology with Potamopyrgus
      antipodarum was developed. Snails were inserted into cages, made of Plexiglas
      measuring 7 * 9 * 7 cm(3) and fixed with stainless steel pins into the sediment
      at the relevant sampling sites. During the experiment physico-chemical properties
      of the water and concentrations of metals, PAHs and PCBs were measured in the
      sediment. The growth and survival of the snails was not affected, but the
      reproduction increased significantly at one of the most polluted sites. The
      increase in reproduction was neither correlated with physico-chemical parameters,
      nor with the concentrations of the different compounds, but maybe related to
      certain groups of estrogenic compounds. The study demonstrates the excellent
      applicability of this novel in situ test.

PMID- 20674025
TI  - Genotyping of Leptospira interrogans strains from Argentina by Multiple-Locus
      Variable-number tandem repeat Analysis (MLVA).
AB  - Leptospirosis outbreaks occur regularly in Argentina and other South American
      countries, but little is known about their epidemiological relationships.
      Application of new molecular tools, such as the Multiple-Locus Variable-number
      tandem repeat Analysis (MLVA) is limited by scant available data on regional
      strains. We have analyzed the genetic diversity of a collection of 31 strains of
      Leptospira interrogans isolated in Argentina during the past five decades from
      humans and animals, including a strain from an environmental source and another
      isolated from an opossum. Genotyping was performed by 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
      eight distinct MLVA genotypes, with a dominant one, genotype A. Strains with this
      genotype were consistently isolated since 1960, representing 55% of the total
      strains and spanning an extensive geographical distribution. Other seven
      genotypes were less frequent, and only genotypes A and Hond Utrecht IV were
      isolated during the last decade. Different kinds of repeat blocks for each VNTR
      locus were identified by sequence analysis. VNTR copy number differences among
      genotypes always involved only one of these blocks. MLVA patterns obtained reveal
      the genetic diversity and relationships between strains, and constitute the
      framework for the genotyping of leptospires in the region.

PMID- 20674026
TI  - A community planning process for the implementation of evidence-based practice.
AB  - Over the past 10 years, increasing attention has been paid to the development and
      implementation of 'evidence-based' practices or EBPs. In 1998, the National
      Academy of Sciences' Institute of Medicine began drawing attention to the
      discrepancy between research findings and practice patterns in the treatment of
      substance abuse. The community coalition described in this study was developed to
      create a partnership between substance abuse treatment providers, policy makers,
      university-based researchers, and consumers to examine treatment advances and
      evaluate their possible application in local community settings. In the first
      year the community coalition conducted a needs assessment, with the goal of
      prioritizing areas for practice change. The needs assessment process included
      focus groups, key informant interviews, and a survey of substance abuse treatment
      providers. The questions addressed at each stage of the assessment varied, but
      collectively all methods formed the basis for consensus-building for a change in
      practice in substance abuse treatment. The results of the needs assessment were
      further refined and influenced the development and implementation of two evidence
      based practices (EBPs) within multiple agencies. Implications for using a
      community needs assessment to highlight coalition building and identify and
      adopting EBPs are discussed.

PMID- 20674027
TI  - The 'electric stroke' and the 'electric spark': anatomists and eroticism at
      George Baker's electric eel exhibition in 1776 and 1777.
AB  - In 1776 and 1777 five living electric eels exhibited in London became a
      sensational spectacle that appealed to anatomists, electricians and connoisseurs
      of erotica. George Baker's exhibition made visible the 'electric spark' of the
      electrical eel and a series of experiments were both witnessed by and
      participated in by members of the Royal Society and the metropolitan elite. Some
      participants even grasped the eels firmly in their hands and felt the 'electric
      stroke' of the eel in addition to observing the spark. In their observation of
      the electric eel some of these spectators transposed the vivid electric spark
      from the sphere of electricians and anatomists into that of satirical and erotic
      literature. Here the erotic electric eel proliferated in the literature and the
      eel took on quite different connotations that nonetheless were reliant on readers
      knowledge and experience of the exhibition, experiments and the preoccupations of
      anatomists. George Baker's electric eel exhibition of 1776 and 1777 is then
      instructive in exploring the production and circulation of knowledge in Georgian
      Britain. The story of the electric eel in Georgian culture charts the creation of
      the electric spark and stroke as objects of observation and encounter, their
      exhibitionary context, and finally their divergent meanings as the electric eel
      became erotically charged for a metropolitan masculine elite.

PMID- 20674028
TI  - 'Almighty God! What a wonderful discovery!': did Charles Darwin really believe
      life came from space?

PMID- 20674029
TI  - Human complement activation and anaphylatoxins generation induced by snake venom
      toxins from Bothrops genus.
AB  - Snake venoms are a complex mixture of components, which have a wide range of
      actions both on prey and human victims. The genus Bothrops causes the vast
      majority of snakebites in Central and South America, being responsible for 80% of
      snake envenomations in Brazil. Envenomations are characterized by prominent local
      effects, including oedema, haemorrhage and necrosis, which can lead to permanent
      disability. Systemic manifestations such as haemorrhage, coagulopathy, shock and
      acute renal failure may also occur. In the present study we have investigated the
      action of venoms from 19 species of snakes from the genus Bothrops, occurring in
      Brazil, on the complement system in in vitro studies. All venoms were able to
      activate the classical complement pathway, in the absence of sensitizing
      antibody. This activation was in part associated with the cleavage of C1
      Inhibitor by proteases present in these venoms, which disrupts complement
      activation control. No modification of the membrane bound complement regulators,
      such as DAF, CR1 and CD59 was detected, after treatment of human erythrocytes
      with the snake venoms. Some of the Bothrops venoms were also able to activate
      alternative and lectin pathways, as measured in haemolytic and ELISA assays. C3a,
      C4a and C5a were generated in sera treated with the venoms, not only through C
      activation, but also by the direct cleavage of complement components, as
      determined using purified C3 and C4. Metallo- and/or serine-protease inhibitors
      prevented cleavage of C3 and C4. These results suggest that Bothrops venoms can
      activate the complement system, generating a large amount of anaphylatoxins,
      which may play an important role in the inflammatory process presented in humans
      after snake envenomations, and they may also assist, due to their vasodilatory
      effects, to enhance the spreading of other venom components.

PMID- 20674030
TI  - Synthesis, anticancer activities, interaction with DNA and mitochondria of
      manganese complexes.
AB  - Two new complexes [(Etdpa)MnCl(2)] and [(Adpa)Mn(Cl)(H(2)O)] (Etdpa = ethyl bis(2
      pyridylmethyl)amino-2-propionate; Adpa = bis(2-pyridylmethyl)amino-2-propionic
      acid) were synthesized and characterized by spectral methods. The crystal
      structure of [(Etdpa)MnCl(2)] shows that the Mn(II) atom is coordinated by three
      N atoms (N1, N2, N3), one oxygen atom (O1) of the ligand (Etdpa) and two chloride
      atoms (Cl1, Cl2), forming a distorted octahedral geometry. The binding
      interaction between ct-DNA and the synthesized complexes was relatively weak, but
      they can inhibit the induced swelling of Ca(2+)-loaded mitochondria in a dose
      dependent manner. The [(Adpa)Mn(Cl)(H(2)O)] can cause the obvious decrease of
      mitochondria membrane potential. The MTT (3-[4,5-Dimethylthiazol-2-yl]-2,5
      diphenpyltetra-zolium bromide) assay shows that the two Mn(II) complexes are more
      active against cancer cells. Especially [(Adpa)Mn(Cl)(H(2)O)] can inhibit the
      proliferation of glioma cells with IC(50) 9.5 MUM. Experimental results indicate
      that the [(Adpa)Mn(Cl)(H(2)O)] could be a new potential antitumor complex to
      target the mitochondria.

PMID- 20674031
TI  - Preparation, 99mTc-labeling and biodistribution studies of a PNA oligomer
      containing a new ligand derivative of 2,2'-dipicolylamine.
AB  - A new azido derivative of 2,2'-dipicolylamine (Dpa), 2-azido-N,N-bis((pyridin-2
      yl)methyl)ethanamine, (Dpa-N(3)) was readily prepared from the known 2
      (bis(pyridin-2-ylmethyl)amino)ethanol (Dpa-OH). It was demonstrated that Dpa-N(3)
      could be efficiently labeled with both [Re(CO)(3)(H(2)O)(3)]Br and
      [(99m)Tc(H(2)O)(3)(CO)(3)](+) to give [Re(CO)(3)(Dpa-N(3))]Br and
      [(99m)Tc(CO)(3)(Dpa-N(3))](+), respectively. Furthermore, Dpa-N(3) was
      successfully coupled, on the solid phase, to a Peptide Nucleic Acid (PNA)
      oligomer (H-4-pentynoic acid-spacer-spacer-tgca-tgca-tgca-Lys-NH(2); spacer= -NH
      (CH(2))(2)-O-(CH(2))(2)-O-CH(2)-CO-) using the Cu(I)-catalyzed [2+3] azide/alkyne
      cycloaddition (Cu-AAC, often referred to as the prototypical "click" reaction) to
      give the Dpa-PNA oligomer. Subsequent labeling of Dpa-PNA with
      [(99m)Tc(H(2)O)(3)(CO)(3)](+) afforded [(99m)Tc(CO)(3)(Dpa-PNA)] in radiochemical
      yields >90%. Partitioning experiments in a 1-octanol/water system were carried
      out to get more insight on the lipophilicity of [(99m)Tc(CO)(3)(Dpa-N(3))](+) and
      [(99m)Tc(CO)(3)(Dpa-PNA)]. Both compounds were found rather hydrophilic (log
      D(o/w) values at pH=7.4 are -0.50: [(99m)Tc(CO)(3)(Dpa-N(3))](+) and -0.85:
      [(99m)Tc(CO)(3)(Dpa-PNA)]. Biodistribution studies of [(99m)Tc(CO)(3)(Dpa-PNA)]
      in Wistar rats showed a very fast blood clearance (0.26 +/- 0.1 SUV, 1h p.i.) and
      modest accumulation in the kidneys (5.45 +/- 0.45 SUV, 1h p.i.). There was no
      significant activity in the thyroid and the stomach, demonstrating a high in vivo
      stability of the (99m)Tc-labeled Dpa-PNA conjugate.

PMID- 20674032
TI  - The Hypomania Checklist-32 and the Mood Disorder Questionnaire as screening tools
      -going beyond samples of purely mood-disordered patients.
AB  - BACKGROUND: Bipolar disorders are often not recognized. Several screening tools
      have been developed, e.g., the Hypomania Checklist-32 (HCL-32) and the Mood
      Disorder Questionnaire (MDQ) to improve this situation. Whereas the German HCL-32
      has been used in non-clinical samples, neither the HCL-32 nor the MDQ has been
      validated in German samples of mood-disordered patients. Additionally, hardly any
      prior study has included patients with non-mood disorders or has considered
      potential effects of comorbid conditions. Therefore the goal of this study was to
      test the validity of both scales in a diverse patient sample while also taking
      into account psychiatric comorbidity. METHOD: A multi-site study was conducted
      involving seven centers. Patients (n=488) completed the HCL-32 and MDQ and were
      independently interviewed with the Structured Clinical Interview for DSM (SCID).
      RESULTS: Sensitivity for bipolar I was similar for HCL-32 and MDQ (.88 and .84)
      but slightly different for bipolar II (.90 and .83), specificity, however, was
      higher for MDQ. In general, a comorbid condition led to increased scores in both
      tools regardless of whether the primary diagnosis was bipolar or not. LIMITATIONS
      AND DISCUSSION: Although we included not just mood-disordered patients, detailed
      subgroup analyses for all diagnostic categories were not possible due to sample
      sizes. In summary, HCL-32 and MDQ seem fairly comparable in detecting bipolar
      disorders although their effectiveness depends on the goal of the screening,
      psychiatric comorbidity, and potentially the setting.

PMID- 20674033
TI  - Prevalence and correlates of eating disorders in 875 patients with bipolar
      disorder.
AB  - OBJECTIVE: Relatively little is known about the co-occurrence of bipolar and
      eating disorders. We therefore assessed the prevalence and clinical correlates of
      eating disorders in 875 patients with bipolar disorder. METHOD: 875 outpatients
      with DSM-IV bipolar I or II disorder were evaluated with structured diagnostic
      interviews and clinician- and self-administered questionnaires to determine
      bipolar and eating disorder diagnoses, other comorbid Axis I disorder diagnoses,
      and demographic and historical illness characteristics. RESULTS: 125 (14.3%)
      patients met DSM-IV criteria for at least one comorbid lifetime Axis I eating
      disorder, with binge eating disorder (N=77) being more common than bulimia
      nervosa (n=42) and anorexia nervosa (N=27). There were no significant eating
      disorder comorbidity differences between bipolar I and bipolar II patients.
      Presence of a lifetime comorbid eating disorder was associated with female
      gender, younger age, earlier age of onset of mood symptoms and of bipolar
      disorder, presentation in a mixed episode, greater number of prior mood episodes,
      history of rapid cycling and suicide attempts, greater mean BMI, obesity and
      severe obesity, and family history of depression, bipolar disorder, alcoholism,
      and drug abuse. When the three eating disorder groups were compared, lifetime
      anorexia nervosa was associated with normal weight and a lifetime anxiety
      disorder, lifetime bulimia nervosa was associated with overweight, and lifetime
      binge eating disorder was associated with obesity and severe obesity.
      CONCLUSIONS: Patients with bipolar disorder, especially women, not infrequently
      have comorbid eating disorders, and this comorbidity is associated with an
      earlier age of onset and more severe course of bipolar illness.

PMID- 20674034
TI  - Quality of marital relationship and depression: results of a 10-year prospective
      follow-up study.
AB  - BACKGROUND: Although the long-term course of depression has been intensively
      examined, there are only few studies on the long-term development of depressed
      patients' spousal relationships. The aim of the study was to assess the quality
      and stability of depressed patients' spousal relationships in the long-term
      course of depression and to identify predictors of relationship outcome. METHODS:
      In the study, 50 inpatients with Major Depression were followed-up one, two and
      ten years after discharge from hospital and compared to a healthy control group
      matched by age and sex. Marital satisfaction was measured by the Terman item.
      Expressed Emotion (EE) was assessed with the Five-Minute Speech Sample (FMSS) and
      the Perceived Criticism Index (PC). RESULTS: In the follow-up period of ten
      years, 26 patients (56.5%) had a recurrence. Ten years after discharge from
      hospital 8 couples were separated, 11 were unhappy and 26 couples were happy with
      their spousal relationship. The quality of marital relationship decreased over
      the follow-up period. In comparison to a healthy control group, patients showed a
      significantly worse quality of marital relationship at follow-up. Besides age and
      course of depression, the spousal EE status was a prognostic factor for the
      quality of the relationship after 10 years. CONCLUSIONS: The results confirm the
      decrease of marital satisfaction over time in the long-term course of depression.
      Identified interpersonal predictors of the quality of spousal relationship in
      major depression could be used as indication criteria for couple therapy.

PMID- 20674035
TI  - Treatment for depression and change in mood instability.
AB  - BACKGROUND: Mood varies along at least 2 dimensions, severity and instability
      (MI). Compared with severity, there is little research on the treatment of MI. We
      assessed changes in MI with community psychiatric treatment, in patients with
      depression and mood swings. METHOD: Diagnoses were obtained with the MINI. Thirty
      four patients completed the Mood Disorders Questionnaire, the Beck Depression
      Inventory (BDI) and the State-Trait Anxiety Inventory (STAI-T). MI was calculated
      from visual analogue scales (VAS) ratings for depression and anxiety. The VAS was
      rated twice a day for a week. The BDI, STAI-T and VAS were repeated after 3-6
      months of treatment. RESULTS: Patients improved with treatment on depression
      (BDI) and anxiety (STAI-T) severity but not on MI. However, change in MI
      predicted change in depression severity (BDI). LIMITATIONS: The sample size was
      relatively small and information on treatment was limited. There was no control
      group. Studies of longer duration and with more comprehensive treatment might be
      necessary to show changes in MI. CONCLUSIONS: MI does not respond consistently
      within 3-6 months to common effective psychiatric treatments for depression and
      anxiety. Improved treatment of MI could result in improved treatment for major
      depression.

PMID- 20674036
TI  - Base rates for depersonalization according to the 2-item version of the Cambridge
      Depersonalization Scale (CDS-2) and its associations with depression/anxiety in
      the general population.
AB  - BACKGROUND: Recently, the two item version of the Cambridge Depersonalization
      Scale (CDS-2) has been validated in a clinical sample and has demonstrated that
      it is a useful tool for the detection of clinically significant depersonalization
      (DP). In order to provide a framework for the interpretation of the CDS-2 scores
      the aim of this study was to achieve normative data of a representative sample of
      the German population and to evaluate the associations with depression, anxiety
      and sociodemographic characteristics. METHODS: A nationally representative face
      to-face household survey was conducted during the mid of 2009 in Germany. The
      sample comprised N = 2512 participants. The survey questionnaire consisted of the
      CDS-2, the Hospital Anxiety and Depression Scale, and demographic
      characteristics. RESULTS: Case level of DP was found for 3.4% of the participants
      without significant sex and age differences. Although DP was strongly associated
      with depression and anxiety, principal component analysis clearly supported the
      distinctiveness of the psychopathological syndromes of depression, anxiety and
      DP. LIMITATIONS: A criterion standard diagnostic interview for DP, anxiety and
      depression was not included. CONCLUSIONS: The results provide a framework for the
      interpretation of the CDS-2 scores and support the view that DP is a common and
      distinct psychopathological syndrome.

PMID- 20674037
TI  - Potential involvement of serotonin receptor genes with age of onset and gender in
      schizophrenia: a preliminary study in a Spanish sample.

PMID- 20674038
TI  - Lack of association of NALCN genetic variants with schizophrenia.
AB  - NALCN (sodium leak channel, non-selective) is located on chromosome 13q
      (suggested linkage region for schizophrenia). We analyzed 21 polymorphisms in 464
      schizophrenia subjects, 220 controls subjects and 119 small nuclear families. We
      observed nominal association with rs9518320 and rs9518331, suggesting that NALCN
      is not related to schizophrenia risk.

PMID- 20674039
TI  - Cannabis involvement in individuals with bipolar disorder.
AB  - In a study of 471 bipolar disorder (BD) cases and 1761 controls, individuals with
      BD were 6.8 times more likely to report a lifetime history of cannabis use. Rates
      of DSM-IV cannabis use disorders in those with BD were 29.4% and were
      independently and significantly associated with increased suicide attempts,
      greater likelihood of mixed episodes and greater disability attributable to BD.

PMID- 20674040
TI  - Morningness/eveningness, pubertal timing, and substance use in adolescent girls.
AB  - The purpose of this study was to examine the associations between
      Morningness/Eveningness (M/E; a measure of sleep-wake preference) and alcohol,
      cigarette, and marijuana use as well as the interaction of M/E and pubertal
      timing. The data represent baseline measures from a longitudinal study examining
      the association of psychological functioning and smoking with reproductive and
      bone health in 262 adolescent girls (11-17 years). The primary measures used for
      this study were pubertal timing (measured by age at menarche), the
      Morningness/Eveningness scale, and substance use (alcohol, cigarettes, and
      marijuana). Multiple group path modeling showed that there was a significant
      interaction between pubertal timing and M/E on cigarette use. The direction of
      the parameter estimates indicated that for the early and on-time groups, Evening
      preference was associated with more cigarette use. For the late timing group the
      association was not significant. The results point to the need to consider sleep
      preference as a characteristic that may increase risk for substance use in
      adolescents.

PMID- 20674041
TI  - Ecologically valid support for the link between cognitive and psychosocial
      functioning in bipolar disorder.
AB  - Prior research into the link between cognitive and psychosocial functioning in
      bipolar disorder has examined primarily asymptomatic patients, has measured these
      domains concurrently, and has failed to establish convergent validity in the
      assessment of psychosocial dysfunction. The present study examines the relation
      between cognitive and psychosocial functioning at the time of discharge from
      hospitalization for acute mood disturbance. We obtained measures of psychosocial
      functioning that were both close and distant to the time of neuropsychological
      testing; the former from the discharging psychiatrists, and the latter from
      reports of formally recognized disability status, determined by persons wholly
      unrelated to the present research. Sixty-three patients with bipolar I disorder,
      hospitalized for acute mood disturbance, completed a neuropsychological test
      battery 24 to 48 h prior to discharge. We compared patients with versus without
      formal disability status on the Global Assessment of Functioning (GAF) scale and
      on scores of neuropsychological tests. We also tested associations between GAF
      scores and cognitive test scores. Results supported the convergent validity in
      the measurement of psychosocial disability, underscored the robust connection
      between cognitive and psychosocial impairment, and highlighted the presence of
      this connection during an important clinical state - time of discharge from
      psychiatric hospitalization.

PMID- 20674042
TI  - Monoclonal antibodies to equine CD14.
AB  - CD14 is a receptor for the complex of lipopolysaccaride (LPS) and LPS-binding
      protein. Binding of this complex to CD14 in association with Toll-like receptor 4
      provides a major pathway for the initiation of innate immune responses to
      bacterial pathogens. We used a mammalian expressed extracellular region of equine
      CD14 (rCD14) derived from an IgG fusion protein to produce monoclonal antibodies
      (mAbs) to CD14. Eight mAbs were tested by flow cytometric analysis of equine
      leukocytes and by immunoblotting using rCD14 indicating that the mAbs recognized
      at least three different epitopes on equine CD14. One mAb, clone 105, was used
      for further characterization of CD14+ cells in peripheral blood mononuclear cells
      (PBMC). Phenotyping indicated that the majority of the CD14+ PBMC were non-B/non
      T-cells. Magnetic cell sorting enriched CD14+ cells to > 95% as detected by flow
      cytometry. Differential cell counts on Wright's-stained cytospin smears of CD14+
      cell fractions demonstrated that 49-73% of them were monocytes. The discrepancy
      between CD14+ cells detected by flow cytometric analysis and monocytes based on
      morphologic criteria suggests that some of the equine CD14+ PBMC are lymphoid
      cells. The mAbs to equine CD14 provide new tools for cellular analysis and CD14+
      cell isolation in horses.

PMID- 20674043
TI  - Analysis of glial secretome: the long pentraxin PTX3 modulates phagocytic
      activity of microglia.
AB  - Microglia, as the phagocytes of the central nervous system, play an important
      role in the recognition, engulfment, and clearance of apoptotic cells and
      invading microbes. Proteins secreted from activated glial cells may affect
      microglial phagocytic activity. Secreted proteins of mixed glial cells stimulated
      with lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) for 24h were
      identified for the first time by liquid chromatography and tandem mass
      spectrometric analysis. Several proteins were newly identified as a glia-secreted
      protein. Among the proteins identified by the mixed glia secretome analysis,
      pentraxin 3 (PTX3) secretion was most highly induced by LPS/IFN-gamma
      stimulation. Expression of PTX3 mRNA was detected in primary microglia and
      astrocyte cultures as well as glial cell lines. Glial secretion of PTX3 and its
      inflammatory induction was confirmed by Western blot analysis of conditioned
      media of mixed glial cultures. PTX3 did not influence LPS-induced nitric oxide
      production or neurotoxicity of BV-2 microglial cells. Most importantly, PTX3
      selectively modulated microglial phagocytosis activity; it promoted engulfment of
      zymosan particles, while it inhibited uptake of apoptotic cells. Our results
      indicate that glia-derived PTX3 may modulate phagocytic functions of microglia,
      and this may have important implications in the regulation of microglial activity
      in health and disease.

PMID- 20674044
TI  - Universal newborn hearing screening in the Champagne-Ardenne region: a 4-year
      follow-up after early diagnosis of hearing impairment.
AB  - INTRODUCTION: Permanent congenital hearing loss is one of the most frequent
      congenital anomaly at birth. Universal newborn hearing screening (UNHS) was
      introduced in numerous countries in order to allow an early diagnosis and
      intervention for congenital hearing impairment. OBJECTIVE: First aim of this
      study is to evaluate the accuracy of early diagnosis of hearing impairment after
      UNHS. Second aim is to discuss the auditory intervention proposed after this
      diagnosis. Last aim is to evaluate the relevance of UNHS for early diagnosis and
      intervention. MATERIALS AND METHODS: Prospective study. UNHS program was
      introduced in the entire French region of Champagne-Ardenne in January 2004.
      Forty-one children have benefited of an early diagnosis of hearing impairment
      until June 2007. They were included in an intervention program consisting of an
      audiometric follow-up and an auditory intervention. This program was conducted
      until June 2008. RESULTS: There were 28 males patients and 13 females patients.
      The diagnosis of hearing aid impairment was carried at an average age of 3.2
      month. The auditory follow-up allowed confirming the initial diagnosis of
      deafness for the majority of the children as for their degree of hearing loss.
      Auditory intervention was heterogeneous depending on degree of hearing loss of
      the children. CONCLUSION: This UNHS program demonstrates its validity and
      feasibility for early diagnosis and intervention of congenital hearing
      impairment. It brought a major impact on the management of congenital hearing
      impairment in Champagne-Ardenne.

PMID- 20674045
TI  - Propranolol for the treatment of airway hemangiomas: a case series and treatment
      algorithm.
AB  - OBJECTIVES: (1) To present six patients with symptomatic airway hemangiomas
      treated with oral propranolol. (2) To review the diagnostic and treatment options
      for airway hemangiomas and propose a new management protocol. STUDY DESIGN:
      Retrospective review. SETTING: Tertiary care children's hospital. SUBJECTS AND
      METHODS: Pediatric patients diagnosed with obstructive airway hemangiomas treated
      with oral propranolol. Patients were followed for symptomatic improvement and
      relief of airway obstruction on imaging or laryngoscopy. RESULTS: Seven patients
      presenting with airway obstruction were treated with propranolol. One patient had
      a focal hemangioma confined to the subglottis. Four patients had airway
      hemangiomas that extended beyond the confines of the larynx and trachea. A sixth
      patient had a bulky supraglottic hemangioma. A seventh patient with an extensive
      maxillofacial lesion failed propranolol therapy and was found to have a pyogenic
      granuloma on final pathology after excision. Six patients had failed standard
      medical therapy and/or surgical interventions and were treated successfully with
      oral propranolol with improvements in airway symptoms and oral intake, requiring
      no further surgical intervention. Treatment was initiated as early as 1.5 months
      of age, and as late as 22 months. No adverse side effects of propranolol were
      noted. CONCLUSIONS: Oral propranolol was successfully used to treat airway
      hemangiomas, resulting in rapid airway stabilization, obviating the need for
      operative intervention, and reducing the duration of systemic corticosteroid
      therapy while causing no obvious adverse effects. These outstanding results
      enable the possibility of use of a standardized diagnostic and treatment
      algorithm for airway hemangiomas that incorporates systemic propranolol.

PMID- 20674046
TI  - Proteins interacting with nicotinic acetylcholine receptors: expanding functional
      and therapeutic horizons.
AB  - Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels that
      carry out the fast actions of the neurotransmitter acetylcholine (ACh). Over the
      past 30 years, it has become clear that the activity of nAChRs is dependent on
      their interaction with a host of proteins, and the number of these that have been
      identified has increased considerably with recent large-scale proteomic analyses.
      This review focuses on these interacting proteins, discussing how they regulate a
      wide range of functions including receptor assembly, and trafficking to and from
      the cell surface, as well as how they directly modulate functional
      characteristics such as sensitivity and the degree of response to ACh. Mutations
      giving rise to disease states highlight the importance of these interacting
      proteins. Here, we consider their potential as future therapeutic targets for
      treating diseases associated with altered nAChR function.

PMID- 20674047
TI  - Spatio-temporal development of CYP1 activity in early life-stages of zebrafish
      (Danio rerio).
AB  - Endpoints of planar halogenated aromatic hydrocarbon (pHAH) and polycyclic
      aromatic hydrocarbon (PAH) toxicity are mediated via activation of the aryl
      hydrocarbon receptor (AhR) followed by activation of the so called "AhR-battery"
      of genes including the cytochrome P450 1 (CYP1) isoforms. The aim of this study
      was to develop a method to identify CYP1 activity in early life-stages of
      zebrafish (Danio rerio) in order to elucidate the spatio-temporal pattern of
      basal and induced CYP1 activities. Preliminary experiments with the fish embryo
      toxicity test (FET) were carried out to determine toxic effect thresholds of the
      AhR agonist beta-naphthoflavone. To assess basal and beta-naphthoflavone-induced
      CYP1 activity during early life-stages of zebrafish, the commonly used 7
      ethoxyresorufin-O-deethylase (EROD) assay was developed further for use in
      confocal laser scanning microscopy (CLSM) and spectrometry. Following exposure to
      selected cytochrome P450 inducers, zebrafish embryos were dechorionated,
      anaesthetized and inspected in vivo under the CLSM. Alternatively, embryos were
      homogenized, and EROD activity was measured using classical spectrometry in
      vitro. CLSM of CYP-induced fluorescence allowed for the in vivo detection of CYP1
      enzyme activity down to the cellular level as early as in the gastrulation stage.
      Basal and induced CYP1 activity was detected at all time points examined from 8h
      post-fertilization to early adulthood and showed a highly dynamic spatio-temporal
      pattern throughout zebrafish development. Basal and induced EROD activity was
      prominent in tissues of the cardiovascular system, the urinary tract, the
      digestive system, and parts of the brain as well as in the central portion of the
      eye and the otic vesicle during distinct stages of development. The
      differentiation between constitutive and induced spatio-temporal patterns of CYP1
      activity even as early as the gastrula stage provide further insights into the
      endogenous role of CYP1 activity.

PMID- 20674048
TI  - Antioxidant, genotoxic and lysosomal biomarkers in the freshwater bivalve (Unio
      pictorum) transplanted in a metal polluted river basin.
AB  - The freshwater painter's mussel (Unio pictorum) was used as sentinel species to
      assess the chemical disturbance in an Italian river (the river Cecina)
      characterized by elevated levels of trace metals of both natural and
      anthropogenic origin. Organisms were transplanted for 4 weeks in different
      locations of the river basin and the bioaccumulation of metals was integrated
      with a wide battery of biomarkers consisting of oxidative, genotoxic and
      lysosomal responses. Such parameters included the levels of individual
      antioxidants (catalase, glutathione-S-transferases, glutathione reductase, Se
      dependent and Se-independent glutathione peroxidases, total glutathione), the
      total oxyradical scavenging capacity (TOSC), metallothionein-like proteins, the
      assessment of DNA integrity, chromosomal damages and lysosomal membrane
      stability. Elevated levels of several metals were measured in sediments, but the
      relatively low tissue concentrations suggested a moderate bioaccumulation,
      possibly due to a high excretion efficiency, of U. pictorum and/or to a limited
      bioavailability of these elements, partly deriving from erosion of bedrocks.
      Among antioxidant responses, those based on glutathione metabolism and the
      activity of catalase were mostly affected in bivalves showing a significant
      accumulation of arsenic, mercury and/or nickel. In these specimens, the content
      of glutathione and the activities of glutathione reductase and glutathione
      peroxidases (H2O2) were respectively 9-, 6- and 4-fold lower than in controls,
      while a 3-fold increase was observed for catalase. Despite some differences in
      the response of individual antioxidants, a significant reduction of the
      capability to neutralize peroxyl radicals was observed in bivalves caged in all
      the impacted sites of the river basin; these organisms also exhibited a
      significant impairment at the DNA, chromosomal and lysosomal levels. Considering
      the mild contamination gradient in the investigated area, the overall results
      suggested that some oxidative biomarkers, as well as those evaluating chromosomal
      and cell damages, are highly sensitive and could be profitably applied to caged
      painter's mussels for environmental quality assessment in freshwater.

PMID- 20674049
TI  - Normal and abnormal development of pulmonary veins: state of the art and
      correlation with clinical entities.
AB  - Interest for the pulmonary veins has increased in the past decade after the
      potential arrhythmogenicity of the myocardial sleeve surrounding these structures
      has been recognized. Furthermore, there are several clinical entities, such as
      anomalous connection pattern and pulmonary vein stenosis, that are related to
      abnormal pulmonary vein development. In this review, we will describe current
      literature and aim to elucidate and reorganize current opinions on normal and
      abnormal pulmonary vein development in relation to clinical (management of)
      diseases. Several unresolved questions will be addressed, as well as current
      conceptual controversies. First, a general overview of development of structures
      at the venous pole of the heart, including normal development of the pulmonary
      vein from a primitive Anlage, will be provided. Recent insights indicate an
      important contributory role of the mesoderm behind the heart, the so-called
      second heart field, to this area. Subsequently, the formation of a myocardial and
      smooth muscle vascular wall of the pulmonary veins and the left atrium is
      described, as well as current insights in the mechanisms involved in the
      differentiation of these different cell types in this area. Next, developmental
      concepts of normal pulmonary venous drainage patterns are reviewed, and an
      overview is provided of clinical entities related to abnormal development at
      several anatomical levels. Lastly, attention is paid to arrhythmogenesis in
      relation to pulmonary vein development, as well the consequences for clinical
      management.

PMID- 20674050
TI  - Comparative evaluation of the usability of 2 different methods to perform mild
      hypothermia in patients with out-of-hospital cardiac arrest.
AB  - BACKGROUND: Several studies have shown that mild hypothermia (32-34 degrees C)
      markedly mitigates brain damage after cardiac arrest (CA). This study aimed to
      compare the efficacy of the non-invasive cooling device Hilotherm Clinic
      (Hilotherm GmbH, Germany) with conventional cooling to induce and maintain mild
      hypothermia in patients after out-of-hospital CA. METHODS: 50 adult patients with
      an indication for controlled mild hypothermia were prospectively assigned to
      conventional cooling (n=20) or cooling with the Hilotherm system (n=30). Patients
      receiving a cooling therapy by Hilotherm were treated either with 0.35 m(2)
      (n=20) or with 0.7 m(2) (n=10) surface area of cooling sleeves. RESULTS: The
      speed of cooling was significantly higher in both Hilotherm groups compared to
      conventional cooling (Hilotherm 0.7 m(2): 0.91 +/- 0.08 degrees C/h, Hilotherm
      0.35 m(2): 0.47 +/- 0.04 degrees C/h, and conventional: 0.3 +/- 0.04 degrees C/h,
      p <= 0.003). Temperature deviation from the target temperature of 33 degrees C
      was significantly higher in the conventional group compared to both Hilotherm
      groups. During induction of mild hypothermia a significant reduction of the mean
      arterial blood pressure and the heart rate was observed without significant
      differences between the groups. However, the speed of cooling (range 0.3-0.91
      degrees C/h) did not correlate to the decrease of blood pressure and heart rate.
      Norepinephrine dosing during induction of mild hypothermia and re-warming (1st
      2nd day) was significantly increased compared to the 3rd day after admission in
      all groups. Dobutamine dosing and 30 days in-hospital mortality did not differ
      significantly between the groups. CONCLUSIONS: Rapid and reliable mild
      hypothermia can be better achieved by the non-invasive cooling system Hilotherm
      compared to conventional cooling with ice packs and cold infusion.

PMID- 20674051
TI  - The importance of pulmonary artery pressures on late atrial arrhythmia in
      transcatheter and surgically closed ASD type secundum.
AB  - AIMS: Atrial fibrillation and flutter remain an important cause of morbidity in
      adults with atrial septal defect (ASD). This study aimed at investigating
      predictors for late (>= 1 month after repair) atrial arrhythmia. METHODS:
      Patients who underwent ASD closure after the age of 18 years, were selected
      through the databases of three medical centres in Belgium. Preprocedural,
      periprocedural and follow-up data were extracted. Univariate and multivariate Cox
      regression analysis was performed. Kaplan-Meier analysis was performed for any
      independent predictor of late atrial arrhythmia. RESULTS: A total of 155 patients
      (38 men and 117 women) was included. Twenty-four patients (median age 48.3 years,
      range 19.9-79.8) underwent surgical and 131 (median age 57.6 years, range 18.2
      86.9) underwent transcatheter closure. Thirty-nine patients (25.2%) presented
      with late atrial arrhythmia. Male gender (P = 0.008), creatinine (P = 0.002),
      atrial arrhythmia before (P < 0.0001) and within 1 month after repair (P = 0.001)
      and a mean pulmonary artery pressure (mPAP) >= 25 mmHg (P < 0.0001) correlated
      with late atrial arrhythmia in univariate Cox-regression analysis. Multivariate
      analysis showed that mPAP >= 25 mm Hg (HR 3.72; 95%CI 1.82-7.59; P < 0.0001) and
      the presence of atrial arrhythmia before (HR 3.22; 95%CI 1.56-6.66; P = 0.002)
      and within 1 month after repair (HR 2.08; 95%CI 2.08-15.92; P = 0.001) were
      predictive of late atrial arrhythmia. Kaplan-Meier analysis showed that patients
      with a mPAP >= 25 mm Hg had a higher risk at developing late atrial arrhythmia (P
      < 0.0001). CONCLUSION: In patients with ASD type secundum, a mPAP >= 25 mmHg is
      an independent predictor of late atrial arrhythmia. The presence of pulmonary
      hypertension before repair should raise awareness for atrial arrhythmias and may
      be used to guide therapy.

PMID- 20674052
TI  - Generalization of visuomotor adaptation to different muscles is less efficient:
      experiment and model.
AB  - Reaching to visual targets engages the nervous system in a series of
      transformations between sensory information and motor commands to muscles. We
      recently showed that visuomotor adaptation requiring modulation of the activity
      of the same muscles is more efficient than adaptation requiring a transition to
      different muscles. Here I specifically tested for adaptation at the level of the
      final transformation into muscle activation by assessing generalization to
      unpracticed areas of the workspace, and propose a computational model with
      modulation of muscle synergies. In the experiment, a visuomotor rotation was
      applied during a center-out isometric torque production task carefully configured
      such that adaptation and generalization could be achieved either by only
      rescaling the contribution of the same muscles, or by additionally requiring the
      recruitment of different muscles. Consistent with our previous finding, the time
      course of directional errors revealed that the degree of adaptation was
      substantially lower (by 28.1%) for the latter case. More importantly, directional
      error obtained for generalization that required, in principle, to recruit
      different muscles from these implicated in the adaptation was more than twice
      that of other generalization areas. Taken together, these results suggest that
      modulation within an original muscle synergy contributed to visuomotor
      adaptation, and that synergy recomposition imposed a limitation on both
      adaptation and generalization. I reproduced these results with a model of the
      sensorimotor transformation which includes two population codes, one for the
      sensory network and one for the motor network. Muscle synergies are defined as
      linear combination of muscles by connections of the motor network, and modulation
      of these synergies are elicited by adaptation of the weight of these connections.
      Finally, I speculate that the limitation imposed on synergy recomposition
      originates in the balance of inhibitory and excitatory mechanisms that operate at
      different levels of the nervous system, and that contribute to the functional
      organization of muscle recruitment by focusing activity on relevant muscles.

PMID- 20674053
TI  - Tonic postural lean after-effects influenced by support surface stability and
      dynamics.
AB  - Tonic neuromuscular processes are evident during lean after-effects, which occur
      after prolonged standing on a fixed ramp. Postural processes underlying lean
      after-effects were examined here using dynamic surface conditions. Three tilt
      adaptation conditions were tested with eyes-closed (n=11). Tilt adaptation
      conditions involved standing for 120s on a fixed toes-up ramp (7 degrees ) or on
      a toes-up sinusoidally tilted surface (7 degrees  +/- 3 degrees ), which was
      followed by 120s of standing on either a fixed horizontal surface or sway
      referenced surface. All participants showed postural after-effects (p < .003).
      Specifically, standing on a fixed horizontal surface after sine-tilt adaptation,
      resulted in forward leaning which decayed over 120s back to baseline. Standing on
      a sway-referenced surface after tilt-adaptation, initially showed no lean after
      effect, however over the course of the trial the center-of-pressure shifted
      backward (p < .02). This after-effect during sway-reference conditions was also
      evident in the sway-induced surface tilt, which increased in dorsiflexion (p <
      .002), rather than decaying back to baseline. Thus, adaptation occurs on a
      dynamically tilted surface, while reliability of the surface as a stable
      reference affects the return of the center-of-pressure and surface tilt to
      baseline. These findings relate to changes in flexor/extensor muscle tonic set
      point which also occur following a prolonged voluntary isometric contraction.

PMID- 20674054
TI  - The BUMP model of response planning: intermittent predictive control accounts for
      10 Hz physiological tremor.
AB  - Physiological tremor during movement is characterized by ~10 Hz oscillation
      observed both in the electromyogram activity and in the velocity profile. We
      propose that this particular rhythm occurs as the direct consequence of a
      movement response planning system that acts as an intermittent predictive
      controller operating at discrete intervals of ~100 ms. The BUMP model of response
      planning describes such a system. It forms the kernel of Adaptive Model Theory
      which defines, in computational terms, a basic unit of motor production or BUMP.
      Each BUMP consists of three processes: (1) analyzing sensory information, (2)
      planning a desired optimal response, and (3) execution of that response. These
      processes operate in parallel across successive sequential BUMPs. The response
      planning process requires a discrete-time interval in which to generate a minimum
      acceleration trajectory to connect the actual response with the predicted future
      state of the target and compensate for executional error. We have shown
      previously that a response planning time of 100 ms accounts for the intermittency
      observed experimentally in visual tracking studies and for the psychological
      refractory period observed in double stimulation reaction time studies. We have
      also shown that simulations of aimed movement, using this same planning interval,
      reproduce experimentally observed speed-accuracy tradeoffs and movement velocity
      profiles. Here we show, by means of a simulation study of constant velocity
      tracking movements, that employing a 100 ms planning interval closely reproduces
      the measurement discontinuities and power spectra of electromyograms, joint
      angles, and angular velocities of physiological tremor reported experimentally.
      We conclude that intermittent predictive control through sequential operation of
      BUMPs is a fundamental mechanism of 10 Hz physiological tremor in movement.

PMID- 20674055
TI  - Evaluating variability and uncertainty separately in microbial quantitative risk
      assessment using two R packages.
AB  - Quantitative risk assessment has emerged as a valuable tool to enhance the
      scientific basis of regulatory decisions in the food safety domain. This article
      introduces the use of two new computing resources (R packages) specifically
      developed to help risk assessors in their projects. The first package,
      "fitdistrplus", gathers tools for choosing and fitting a parametric univariate
      distribution to a given dataset. The data may be continuous or discrete.
      Continuous data may be right-, left- or interval-censored as is frequently
      obtained with analytical methods, with the possibility of various censoring
      thresholds within the dataset. Bootstrap procedures then allow the assessor to
      evaluate and model the uncertainty around the parameters and to transfer this
      information into a quantitative risk assessment model. The second package,
      "mc2d", helps to build and study two dimensional (or second-order) Monte-Carlo
      simulations in which the estimation of variability and uncertainty in the risk
      estimates is separated. This package easily allows the transfer of separated
      variability and uncertainty along a chain of conditional mathematical and
      probabilistic models. The usefulness of these packages is illustrated through a
      risk assessment of hemolytic and uremic syndrome in children linked to the
      presence of Escherichia coli O157:H7 in ground beef. These R packages are freely
      available at the Comprehensive R Archive Network (cran.r-project.org).

PMID- 20674056
TI  - Identification and haplotype distribution of Alicyclobacillus spp. from different
      juices and beverages.
AB  - Alicyclobacillus spp. is an important thermoacidophilic, spore-forming spoilage
      bacterium that is a major concern for beverage and juice industries. In order to
      develop effective control strategies and adequately address the prevalence of
      contamination sources, it is necessary to characterize Alicyclobacillus' ecology
      in fruit, juice and beverage production and processing environments.
      Alicyclobacillus spp. isolates were collected from juice, beverage, ingredients,
      and environmental samples over a period of ten years. A total of 141 isolates
      were characterized as Alicyclobacillus spp. by 16S rRNA analysis and the most
      frequently isolated species was found to be Alicyclobacillus acidoterrestris
      (45%), A. acidocaldarius subsp. acidocaldarius (30%), and A. acidocaldarius
      (11%). The majority of thermotolerant sporeformers isolated from apple juices and
      concentrates was found to be A. acidoterrestris (24 out of 36 total apple
      isolates); while A. acidoterrestris was most frequently associated with citrus,
      citrus concentrates, and their associated environments, isolated by University of
      Florida (UF) (15 out of total 28 UF citrus isolates). However, A. acidocaldarius
      and subsp. acidocaldarius were frequently isolated by Cornell University (CU) (29
      out of 35 CU citrus isolates), from citrus juices made from concentrate. Four
      major haplotypes of Alicyclobacillus spp. were identified based on the 16S rRNA
      gene sequencing from the 141 isolates tested. The Allelic Types (ATs) matched the
      phylogenetic analysis grouping of the different Alicyclobacillus spp. based on
      the isolation source. Our results suggest a predisposition for certain ATs of
      Alicyclobacillus spp. depending on juice or ingredient isolation source.

PMID- 20674057
TI  - Modeling inactivation kinetics of liquid egg white exposed to UV-C irradiation.
AB  - The efficiency of UV-C irradiation as a non-thermal pasteurization process for
      liquid egg white (LEW) was investigated. LEW inoculated with Escherichia coli K
      12 (ATCC 25253), pathogenic strain of Escherichia coli O157:H7 (NCTC12900) and
      Listeria innocua (NRRL B33314) were treated with UV light using a bench top
      collimated beam apparatus. Inoculated LEW samples were exposed to UV-C
      irradiation of known UV intensity of 1.314mW/cm(2) and sample depth of 0.153cm
      for 0, 3 5, 7, 10, 13, 17 and 20min. The populations of E. coli K-12, E. coli
      O157:H7 and L. innocua were reduced after 20min of exposure by 0.896, 1.403 and
      0.960logCFU respectively. Additionally, the inactivation data obtained for each
      strain suspended in LEW was correlated by using Weibull (2 parameter), Log-Linear
      (1 parameter), Hom (2 parameter) and modified Chick Watson (2 parameter) models.
      The inactivation kinetics of E. coli K-12, E. coli O157:H7 and L. innocua were
      best described by modified Chick Watson model with the smallest root mean squared
      error (RMSE) (R(2)> or =0.92).

PMID- 20674059
TI  - Newly diagnosed hyperglycemia and stress hyperglycemia in a coronary intensive
      care unit.
AB  - AIMS: To determine prevalence of newly diagnosed hyperglycemia (NDH) among
      patients with acute coronary disease, inquire relationship of stress
      hyperglycemia (SH) with functional outcomes. METHODS: Admission (APG) and first
      morning fasting plasma glucose (FPG) measurements were obtained, capillary
      glucose measurements (CGM) every 6-h within first day were performed-Group 1:
      Normoglycemics. Group 2: NDH cases: No known diabetes, APG>200mg/dl and/or
      FPG>126 and/or any of CGM>200. Group 2a: unrecognized glycemic disorder,
      HbA1c>6.0%. Group 2b: stress hyperglycemia, HbA1c<6.0%. Group 3: Recognized
      diabetes. Duration of ICU stays, APACHE-II scores were recorded. Logistic
      regression analysis was performed using ICU stay as dependent variable and age,
      groups, co-morbidities, problems in hospital, APACHE-II scores, CGMs were used as
      independent risk factors. RESULTS: There were 255 (51.6%) in Group 1, 82 (16.6%)
      in Group 2; 37 (7.5%) cases in Group 2a, 45 (9.1%) in Group 2b and 157 (31.8%) in
      Group 3. Group 2b spent longer time in ICU, had higher APACHE-II scores
      (p=0.0001, p=0.0001). Regression analysis demonstrated SH as an independent risk
      factor for duration of ICU stay (OR: 2.8, 95% CI: 1.3-6.2). CONCLUSIONS:
      Hyperglycemia was present in 48.4%; 16.6% had NDH, 9.1% had SH. Poor functional
      conditions of SH cases pointed that they need to be considered carefully.

PMID- 20674060
TI  - The opinion of adolescents and adults on Dutch restrictive and educational
      alcohol policy measures.
AB  - OBJECTIVES: The main objective of this study is to explore the opinion of 16-22
      year olds on alcohol policy measures compared to the opinion of adults older than
      22 years. METHODS: Data was collected in 2008 by using a Dutch panel. This panel
      was based on a representative probability of households with 8280 members of 16
      years and older. The study had a cross-sectional design and questionnaires were
      filled out through internet. RESULTS: According measures related to the
      availability of alcohol, the 16-18- and 19-22-year olds are significantly more
      negative about these policy measures than the respondents older than 22 years.
      Educational measures were more popular than restrictive availability measures
      among all three groups, and the opinions of the groups differed significantly
      from each other. Own alcohol use seemed to be the main predictor for the opinion
      on restrictive availability measures. CONCLUSIONS: The 16-22-year olds are more
      negative regarding restrictive availability measures and educational measures
      than adults older than 22 years, and the restrictive availability measures are
      less popular than the educational measures among the adolescents.

PMID- 20674061
TI  - A model for diagnosis of pulmonary infections in solid-organ transplant
      recipients.
AB  - BACKGROUND: Opportunistic pulmonary infections are a major cause of morbidity and
      mortality among solid organ transplant recipients. The diagnosis of these
      infections is challenging because of the broad spectrum of bacteria, fungi and
      viruses affecting these patients and the lack of specific signs and symptoms.
      Treatment directed at the offending organism started as soon as possible improves
      survival. OBJECTIVE: To develop a decision support system for the diagnosis of
      pulmonary infections in solid-organ transplant recipients. The model's goal is to
      improve the accuracy of the diagnosis and thus the appropriateness of empirical
      treatment. DESIGN: The model is built using a Bayesian network (also known as
      causal probabilistic network). The network is based on pathogen segments which
      are the main building blocks of the model. Segments share common risk factors,
      such as time after transplantation, latent infections of donor/recipient and
      organ transplanted. The segments are linked at symptoms, signs and diagnostic
      tests common to all pathogens. The outputs of the model are predicted
      probabilities of infectious pathogens. To populate the model with data we have
      mainly abstracted data from the literature, using a systematic approach. The
      structure of the model and its adaptation for decision support will be presented.
      EVALUATION: The first evaluation phase assessed the model's diagnosis in a series
      of 20 representative cases of opportunistic infections. A match between the
      case's diagnosis and the model's prediction was achieved in 17/20 of cases. The
      next evaluation phase will consist of a prospective observational study comparing
      the accuracy of the model's diagnosis vs. that of the physician within 24h of
      episode onset, as compared with a gold-standard diagnosis ascribed to the
      patients at the end of the infectious episode by two independent experts. Data
      for this phase are currently collected prospectively.

PMID- 20674062
TI  - Physiologic insulin delivery with insulin feedback: a control systems
      perspective.
AB  - Individuals with type 1 diabetes mellitus must effectively manage glycemia to
      avoid acute and chronic complications related to aberrations of glucose levels.
      Because optimal diabetes management can be difficult to achieve and burdensome,
      research into a closed-loop insulin delivery system has been of interest for
      several decades. This paper provides an overview, from a control systems
      perspective, of the research and development effort of a particular algorithm-
      the external physiologic insulin delivery system. In particular the introduction
      of insulin feedback, based on beta-cell physiology, is covered in detail. A
      summary of human clinical trials is provided in the context of the evolution of
      this algorithm, and this paper outlines some of the research avenues that show
      particular promise.

PMID- 20674063
TI  - Assessment of bilateral photoplethysmography for lower limb peripheral vascular
      occlusive disease using color relation analysis classifier.
AB  - This paper proposes the assessment of bilateral photoplethysmography (PPG) for
      lower limb peripheral vascular occlusive disease (PVOD) using a color relation
      analysis (CRA) classifier. PPG signals are non-invasively recorded from the right
      and left sides at the big toe sites. With the time-domain technique, the right-to
      left side difference is studied by comparing the subject's PPG data. The absolute
      bilateral differences construct various diminishing and damping patterns. These
      difference patterns in amplitude and shape distortion relate to the grades of
      PVOD, including the normal condition, lower-grade disease, and higher-grade
      disease. A CRA classifier is used to recognize the various patterns for PVOD
      assessment. Its concept is derived from the HSV color model and uses the hue,
      saturation, and value to depict the disease grades using the natural primary
      colors of red, green, and blue. PPG signals are obtained from 21 subjects aged 24
      65 years using an optical measurement technique. The proposed CRA classifier is
      tested using the physiological measurements, and the tests reveal its
      practicality for monitoring PPG signals.

PMID- 20674064
TI  - Wavelets and fuzzy relational classifiers: a novel diffusion-weighted image
      analysis system for pediatric metabolic brain diseases.
AB  - The diffusion-weighted imaging (DWI) technique can be utilized to investigate a
      variety of diseases. We propose an automated pilot system, which assists in the
      diagnosis of metabolic brain diseases, utilizing the DWI. In this study, DWI
      images are preprocessed and exponential apparent diffusion coefficient (eADC)
      images are produced. The eADC images are later brain extracted and normalized to
      a standard brain template. Subsequently, we utilized wavelets to denoise the eADC
      images. The images are rectified, thresholded and now conspicuous abnormal
      regions are subsequently identified utilizing different brain atlases. Abnormal
      regions constitute the features that will be used by a fuzzy relational
      classifier in order to categorize the diseases. A sensitivity and specificity of
      60% and 93.33%, respectively, in detecting metabolic brain diseases have been
      achieved.

PMID- 20674065
TI  - Induced L2-norm minimization of glucose-insulin system for Type I diabetic
      patients.
AB  - Using induced L2-norm minimization, a robust controller was developed for insulin
      delivery in Type I diabetic patients. The high-complexity nonlinear diabetic
      patient Sorensen-model was considered and Linear Parameter Varying methodology
      was used to develop open-loop model and robust H(infinity) controller.
      Considering the normoglycaemic set point (81.1 mg/dL), a polytopic set was
      created over the physiologic boundaries of the glucose-insulin interaction of the
      Sorensen-model. In this way, Linear Parameter Varying model formalism was
      defined. The robust control was developed considering input and output
      multiplicative uncertainties with two additional uncertainties from those used in
      the literature: sensor noise and worst-case design for meal disturbance (60 g
      carbohydrate). Simulation scenario on large meal absorption illustrates the
      applicability of the robust LPV control technique, while patient variability is
      tested with real data taken from the SPRINT clinical protocol on ICU patients.

PMID- 20674066
TI  - Parallelized computation for computer simulation of electrocardiograms using
      personal computers with multi-core CPU and general-purpose GPU.
AB  - Biological computations like electrocardiological modelling and simulation
      usually require high-performance computing environments. This paper introduces an
      implementation of parallel computation for computer simulation of
      electrocardiograms (ECGs) in a personal computer environment with an Intel CPU of
      Core (TM) 2 Quad Q6600 and a GPU of Geforce 8800GT, with software support by
      OpenMP and CUDA. It was tested in three parallelization device setups: (a) a four
      core CPU without a general-purpose GPU, (b) a general-purpose GPU plus 1 core of
      CPU, and (c) a four-core CPU plus a general-purpose GPU. To effectively take
      advantage of a multi-core CPU and a general-purpose GPU, an algorithm based on
      load-prediction dynamic scheduling was developed and applied to setting (c). In
      the simulation with 1600 time steps, the speedup of the parallel computation as
      compared to the serial computation was 3.9 in setting (a), 16.8 in setting (b),
      and 20.0 in setting (c). This study demonstrates that a current PC with a multi
      core CPU and a general-purpose GPU provides a good environment for parallel
      computations in biological modelling and simulation studies.

PMID- 20674067
TI  - An open source tool for heart rate variability spectral analysis.
AB  - In this paper we describe a software package for developing heart rate
      variability analysis. This package, called RHRV, is a third party extension for
      the open source statistical environment R, and can be freely downloaded from the
      R-CRAN repository. We review the state of the art of software related to the
      analysis of heart rate variability (HRV). Based upon this review, we motivate the
      development of an open source software platform which can be used for developing
      new algorithms for studying HRV or for performing clinical experiments. In
      particular, we show how the RHRV package greatly simplifies and accelerates the
      work of the computer scientist or medical specialist in the HRV field. We
      illustrate the utility of our package with practical examples.

PMID- 20674068
TI  - Palliative thoracic radiotherapy in non-small cell lung cancer. An analysis of
      1250 patients. Palliation of symptoms, tolerance and toxicity.
AB  - PURPOSE: To present our experience with short-time, split-course palliative
      thoracic radiotherapy (PTR) in patients with advanced non-small cell lung cancer
      (NSCLC) with special regard to palliation of symptoms, tolerance and toxicity of
      PTR treatment. PATIENTS AND METHODS: Between 1980 and 2005, a group of 1250
      patients with locally advanced or metastatic NSCLC was treated with PTR in our
      Center. All patients presented with moderate or severe symptoms related to local
      cancer growth. RESULTS: The response rate defined as palliation of NSCLC symptoms
      after PTR was 54.1% for cough, 68% for haemoptysis, 51.1% for thoracic pain,
      38.3% for dyspnoea, 12% for hoarseness, and 8% for dysphagia. Tolerance of PTR,
      expressed in terms of patient compliance to the treatment, was good in 92% of
      patients (i.e., 2 series of radiotherapy were given at the planned dose and
      time). Early treatment toxicity was observed in 4.6% of patients and included
      pneumonitis in 2.3%, intense nausea and vomiting in 0.6%, lung hemorrhage in
      0.6%, and severe oesophagitis in 0.5% of patients. Lhermitte's syndrome and
      broncho-oesophageal fistula were observed in 0.4% and 0.2%, respectively. Six out
      of 70 patients who survived longer than 2 years developed chronic pulmonary
      fibrosis with respiratory insufficiency and one patient presented symptoms of
      radiation-induced myelopathy. CONCLUSIONS: The analysis of our results and data
      from the literature show that short-time, split-course PTR is a safe and
      effective method of palliative treatment in patients with advanced NSCLC.

PMID- 20674070
TI  - Surgical treatment of early stage thymoma.

PMID- 20674069
TI  - Anticancer activity of Noscapine, an opioid alkaloid in combination with
      Cisplatin in human non-small cell lung cancer.
AB  - The purpose of this study was to examine the efficacy of Noscapine (Nos) and
      Cisplatin (Cis) combination treatment in vitro in A549 and H460 lung cancer
      cells, in vivo in murine xenograft model and to investigate the underlying
      mechanism. The combination index values (< 0.6) suggested synergistic effects of
      Nos+Cis and resulted in the highest increase in percentage of apoptotic NSCLC
      cells and increased expression of p53, p21, caspase 3, cleaved caspase 3, cleaved
      PARP, Bax, and decreased expression of Bcl2 and surviving proteins compared with
      treatment with either agent. Nos+Cis treatment reduced tumor volume by 78.1 +/-
      7.5% compared with 38.2 +/- 6.8% by Cis or 35.4 +/- 6.9% by Nos alone in murine
      xenograft lung cancer model. Nos+Cis treatment decreased expression of pAkt, Akt,
      cyclin D1, survivin, PARP, Bcl2, and increased expression of p53, p21, Bax,
      cleaved PARP, caspase 3, cleaved caspase 3, cleaved caspase 8, caspase 8, cleaved
      caspase 9 and caspase 9 compared to single-agent treated and control groups. Our
      results suggest that Nos enhanced the anticancer activity of Cis in an additive
      to synergistic manner by activating multiple signaling pathways including
      apoptosis. These findings suggest potential benefit for use of Nos and Cis
      combination in treatment of lung cancer.

PMID- 20674071
TI  - Fluorescent in situ hybridization (FISH) in the differential diagnosis of ground
      glass opacities in the lung.
AB  - Computed tomographic (CT) screening for lung cancer has increased the detection
      rate of nodules manifesting as ground-glass opacities (GGOs). The natural history
      of this new entity it is not well known nor is the factors that influence the
      growth, progression and malignant potential. This genetic study was performed in
      order to identify molecular markers with possible diagnostic and prognostic
      significance to differentiate lesions with malignant or benign profiles. Ten pure
      GGO fresh samples and 5 specimens of normal lung tissue were cytogenetically
      investigated using a direct method and short-term cultures, and molecular
      analysis was performed using the 4-target FISH LAVysion kit for the detection of
      non-small cell lung cancer (NSCLC). Interestingly, all the karyotypes turned out
      to be normal both with the direct method and cultured cells, while in 3 out of 10
      GGOs FISH analysis was abnormal for all the targets and in 2 cases only c-MYC
      amplification was observed. Karyotypes and FISH performed on the normal tissue
      samples gave normal results. Two of three FISH positive patients died, one had a
      relapse of the disease and at the last follow-up showed lung and bone metastases.
      Despite the small sample due to the rarity of pure GGOs, these preliminary
      results indicate that interphase FISH analyses are more informative than
      metaphase studies and might contribute clinically relevant information about the
      nature of these lesions.

PMID- 20674072
TI  - Environmental myopia: a diagnosis and a remedy.
AB  - Long-term ecological observation affords a picture of the past that uniquely
      informs our understanding of present and future ecological communities and
      processes. Without a long-term perspective, our vision is prone to environmental
      myopia. Long-term experiments (LTEs) in particular can reveal the mechanisms that
      underlie change in communities and ecosystem functioning in a way that cannot be
      understood by long-term monitoring alone. Despite the urgent need to know more
      about how climate change will affect ecosystems and their functioning, the
      continued existence of LTEs is extremely precarious and we believe that dedicated
      funds are needed to support them. A new non-profit organization called the
      Ecological Continuity Trust seeks to provide a solution to this problem by
      establishing an endowment that will be specifically earmarked to sustain LTEs as
      a scientific tool for the benefit of future generations.

PMID- 20674074
TI  - Nitrogen supply and abiotic stress influence canavanine synthesis and the
      productivity of in vitro regenerated Sutherlandia frutescens microshoots.
AB  - Environmental stresses can significantly alter the synthesis of both primary and
      secondary metabolites, resulting in medicinal plants with unpredictable
      biological activity. Here, in vitro shoot cultures of the medicinal plant
      Sutherlandia frutescens were used to study the impact of three abiotic stresses
      (nitrogen availability, drought and salinity), primarily on l-canavanine
      synthesis. This compound, a non-protein amino acid, is amongst those metabolites
      linked to the health benefits of Sutherlandia extracts. Nitrogen supplied to
      microplants positively correlated with canavanine levels, exhibited by a fourfold
      reduction when nitrates provided were halved. Although the biomass generated was
      lowered under these conditions, a higher capacity for rooting (52%) in comparison
      to the controls (37%) became evident. Only a small increase of the canavanine
      content in microplants growing on 100mM NaCl medium was detected, indicating that
      salinity stress was not a major limitation on cavanine production, but that it
      played more of a role in vitro on plantlet morphogenesis. Similarly, PEG as a
      supplement had little to no effect on canavanine synthesis. We conclude that a
      deeper understanding of the nutritional requirements for the agricultural crop
      management of S. frutescens, which serves the herbal products industry, is
      needed.

PMID- 20674073
TI  - High glucose disrupts oligosaccharide recognition function via competitive
      inhibition: a potential mechanism for immune dysregulation in diabetes mellitus.
AB  - Diabetic complications include infection and cardiovascular disease. Within the
      immune system, host-pathogen and regulatory host-host interactions operate
      through binding of oligosaccharides by C-type lectin. A number of C-type lectins
      recognise oligosaccharides rich in mannose and fucose - sugars with similar
      structures to glucose. This raises the possibility that high glucose conditions
      in diabetes affect protein-oligosaccharide interactions via competitive
      inhibition. Mannose-binding lectin, soluble DC-SIGN and DC-SIGNR, and surfactant
      protein D, were tested for carbohydrate binding in the presence of glucose
      concentrations typical of diabetes, via surface plasmon resonance and affinity
      chromatography. Complement activation assays were performed in high glucose. DC
      SIGN and DC-SIGNR expression in adipose tissues was examined via
      immunohistochemistry. High glucose inhibited C-type lectin binding to high
      mannose glycoprotein and binding of DC-SIGN to fucosylated ligand (blood group B)
      was abrogated in high glucose. Complement activation via the lectin pathway was
      inhibited in high glucose and also in high trehalose - a nonreducing sugar with
      glucoside stereochemistry. DC-SIGN staining was seen on cells with DC morphology
      within omental and subcutaneous adipose tissues. We conclude that high glucose
      disrupts C-type lectin function, potentially illuminating new perspectives on
      susceptibility to infectious and inflammatory disease in diabetes. Mechanisms
      involve competitive inhibition of carbohydrate binding within sets of defined
      proteins, in contrast to broadly indiscriminate, irreversible glycation of
      proteins.

PMID- 20674075
TI  - Heme oxygenase/carbon monoxide system participates in regulating wheat seed
      germination under osmotic stress involving the nitric oxide pathway.
AB  - To investigate the mechanism and signaling pathway of carbon monoxide (CO) and
      hematin in alleviating seed germination inhibition and lipid peroxidation,
      polyethylene glycol-6000 (PEG) was used to mimic osmotic stress in a series of
      experiments. The results showed that wheat seeds pretreated with a lower dose of
      PEG (12.5%) showed higher tolerance against osmotic stress as well as the up
      regulation of heme oxygenase (HO, EC 1.14.99.3) and decreased lipid peroxidation
      during recuperation, compared to those with a higher dose of PEG (50%). Exposure
      of wheat seeds to 25% PEG, HO-1 inhibitor or specific scavenger of nitric oxide
      (NO) alone differentially led to seed germination inhibition. The PEG-induced
      inhibitory effects on seed germination were ameliorated by the HO-1 inducer
      hematin, CO or NO donor. Additionally, hematin was able to markedly boost the
      HO/CO system. However, the addition of the HO-1 inhibitor or the specific
      scavenger of NO not only reversed the protective effects conferred by hematin,
      but also blocked the up-regulation of HO/CO. In addition, hematin-driven NO
      production in wheat seeds under osmotic stress was confirmed. Based on these
      results, we conclude that the endogenous HO/CO signal system is required for the
      alleviation of osmotic stress-induced wheat seed germination inhibition and lipid
      peroxidation, which might have a possible interaction with NO.

PMID- 20674076
TI  - Acclimation to frost alters proteolytic response of wheat seedlings to drought.
AB  - A comparative examination of cysteine proteinases in winter wheat (Triticum
      aestivum L.) seedlings differing in sensitivity to frost and drought revealed
      many similarities and differences in response to water deprivation.
      Azocaseinolytic activity was enhanced under water deficiency, but the enhancement
      was significantly lower in the tolerant genotype (Kobra cultivar). On the
      contrary, acclimation of wheat seedlings at low temperature had no effect on the
      proteolytic activity of the tolerant cultivar and depressed the azocaseinolytic
      activity of the sensitive cultivar (Tortija). However, the observed depression of
      enzyme activity was fully reversible under dehydration. The content of soluble
      proteins was reduced in dehydrated non-acclimated and in acclimated seedlings of
      the frost-sensitive cultivar, but increased in acclimated seedlings of the
      tolerant cultivar. The cysteine proteinases were preferentially induced under
      water deficiency when assessment was based on the inhibitory effect of
      iodoacetate on azocasein hydrolysis. Separation of cysteine proteinases by SDS
      PAGE containing gelatin as a substrate showed two bands with apparent molecular
      masses of 36 and 38 kDa in the sensitive cultivar, and a third band was detected
      (42 kDa) in the resistant cultivar. Water deficit and low temperature induced the
      new cysteine proteinases of molecular masses about 29, 33 and 42 kDa in sensitive
      non-acclimated seedlings. Polyclonal antibodies raised against Arabidopsis
      proteinase responsive to drought (RD21) cross-reacted with the protein in the 33
      kDa region, and a slight signal was obtained in the 42 kDa region, but only in
      dehydrated seedlings acclimated to frost. Several polypeptides of molecular
      masses of 30, 22, 20 and 18 kDa were recognized by the Arabidopsis aleurain-like
      proteinase (AtALEU) antibodies. The results presented indicate that cysteine
      proteinases are potentially responsible for both low temperature and drought
      tolerance.

PMID- 20674077
TI  - Pathogenesis-associated transcriptional patterns in Triticeae.
AB  - The Triticeae tribe of the plant Poaceae family contains some of the most
      important cereal crop plants for nutrition of humans and livestock such as wheat
      and barley. Despite the agronomical relevance of plant immunity, knowledge on
      mechanisms of disease or resistance in Triticeae is limited. It is hardly
      understood what actually stops a microbial invader when restricted by the plant
      and in how far a susceptible host plant contributes to pathogenesis.
      Transcriptional reprogramming of the host plant may be involved in both immunity
      and disease. This paper gives an overview about recent analyses of global
      pathogenesis-related transcriptional patterns in response of Triticeae to
      biotrophic or non-biotrophic fungal pathogens and their toxins. It highlights
      enriched biological functions in association with successful plant defence or
      disease as well as experiments that successfully translated gene expression data
      into analysis of gene functions.

PMID- 20674078
TI  - A nuclear-localized protein, KOLD SENSITIV-1, affects the expression of cold
      responsive genes during prolonged chilling in Arabidopsis.
AB  - Plants respond to cold by transcriptional and metabolic responses which underlie
      tolerance and acclimation mechanisms, but details at the molecular level are
      incomplete. Here we describe KOLD SENSITIV-1 (KOS1), a new gene required for
      responses to cold. KOS1 protein is predicted to have coiled-coil, Structural
      Maintenance of Chromosomes and nuclear-targeting domains. GFP-labeled KOS1
      localizes to the nucleus. Null mutants could not be isolated but two independent
      knockdown T-DNA mutants were obtained. Growth and development of kos1 knockdown
      mutant plants was comparable to wild type when grown at 21 degrees C. However,
      when grown at 4 degrees C these mutants exhibited accelerated leaf yellowing and
      smaller rosette size than wild type. Quantitative RT-PCR revealed that in the
      cold kos1 mutants had reduced expression of cold-responsive transcripts COR15A,
      COR15B, BAM3 and AMY3. Metabolite profiling revealed that ascorbate levels were
      lower in the mutants in the cold relative to wild type. KOS1 therefore represents
      a new gene that influences the regulation of transcript and metabolite levels in
      response to prolonged chilling temperatures.

PMID- 20674079
TI  - When and how to kill a plant cell: infection strategies of plant pathogenic
      fungi.
AB  - Fungi cause severe diseases on a broad range of crop and ornamental plants,
      leading to significant economical losses. Plant pathogenic fungi exhibit a huge
      variability in their mode of infection, differentiation and function of infection
      structures and nutritional strategy. In this review, advances in understanding
      mechanisms of biotrophy, necrotrophy and hemibiotrophic lifestyles are described.
      Special emphasis is given to the biotrophy-necrotrophy switch of hemibiotrophic
      pathogens, and to biosynthesis, chemical diversity and mode of action of various
      fungal toxins produced during the infection process.

PMID- 20674080
TI  - Differential proteomic responses to water stress induced by PEG in two creeping
      bentgrass cultivars differing in stress tolerance.
AB  - Protein metabolism and expression play important role in plant adaptation to
      water stress. The objectives of this study were to examine proteomic responses to
      water stress induced by polyethylene glycol (PEG) in creeping bentgrass (Agrostis
      stolonifera L.) leaves and to identify proteins associated with stress tolerance.
      Plants of two cultivars ('Penncross' and 'Penn-A4') differing in water stress
      tolerance were grown in sand irrigated daily with water (control) or PEG solution
      (osmotic potential of -0.66MPa) to induce water stress, for 28d in growth
      chambers. Shoot extension rate, relative water content and cell membrane
      stability were measured to compare drought tolerance between the two cultivars.
      All parameters maintained at a significantly higher level in 'Penn-A4' than in
      'Penncross' under PEG treatment. After 28d of water stress, proteins were
      extracted from leaves and separated by difference gel electrophoresis. Among 56
      stress-responsive protein spots, 46 were identified using mass spectrometry. Some
      proteins involved in primary nitrogen and carbon metabolism were down-regulated
      by PEG-induced water stress in both cultivars. The abundance of antioxidant
      enzyme proteins (ascorbate peroxidase, catalase and glutathione-S-transferase)
      increased under water stress, particularly ascorbate peroxidase in 'Penn-A4'. The
      abundance levels of actins, UDP-sulfoquinovose synthase and glucan exohydrolase
      were greater in 'Penn-A4' than in 'Penncross' under PEG treatment. Our results
      suggest that proteins involved in membrane synthesis, cell wall loosening, cell
      turgor maintenance, and antioxidant defense may play roles in perennial grass
      adaptation to PEG-induced water stress.

PMID- 20674081
TI  - [Progression of diabetic retinopathy during pregnancy: a retrospective analysis
      of a series of 77 consecutive patients].
AB  - INTRODUCTION: The aim of this study was to assess diabetic retinopathy
      progression during pregnancy and to determine the predictive factors of this
      progression. PATIENTS AND METHODS: Monocentric retrospective study including 77
      consecutive diabetic women submitted to a multidisciplinary medical follow-up
      during pregnancy with at least one ophthalmologic examination per trimester with
      ocular fundus photographs. RESULTS: Diabetic retinopathy was evidenced in 21
      (27.3%) of the patients during the first trimester (no proliferative form), in 22
      women (28.6%) during the second (two proliferative forms), and 24 (31.2%) during
      the third (two proliferative forms). Progression of at least 1 grade was
      evidenced in four patients from the first to the second trimester, in three from
      the second to the third, and finally in seven patients during the overall follow
      up period. Two patients showed progression to a proliferative form from the first
      to the second quarter. We failed to identify any predictive factor of diabetic
      retinopathy progression except when combining prior systemic hypertension and
      pregnancy-induced hypertension (p<0.03). CONCLUSION: The results of our study
      confirm that diabetic retinopathy progression is uncommon during pregnancy,
      especially if diabetic retinopathy is absent or mild at the beginning. Optimal
      blood sugar levels and blood pressure check-ups play a major role in preventing
      diabetic retinopathy progression. Collaborative medical follow-up can minimize
      ophthalmologic impairment during pregnancy.

PMID- 20674082
TI  - [Ocular contusions at the Cotonou, Benin, National University Hospital. A series
      of 654 cases].
AB  - AIM: To specify the epidemiologic characteristics of ocular contusions, take an
      inventory of etiological factors, and study clinical aspects. PATIENTS AND
      METHODS: This study was a retrospective, descriptive and analytical study. We
      carried out an exhaustive recruitment among the consultations in the
      ophthalmologic department at the Cotonou National University Hospital from 1st
      January 2006 to 30 April 2009 of all the patients with the ocular diagnosis of
      contusion. RESULTS: Of 21,892 consultations, 654 cases were ocular contusions,
      i.e., a total prevalence of 3%. The prevalence among ocular injuries was 70.8%.
      The majority of the patients were between 16 and 45 years old (74.9%) and the
      mean age was 31.2+/-3.5 years. A clear male prevalence was observed (79.7%). The
      principal cause was road traffic accidents (58.6%). The lesions most frequently
      encountered were in the conjunctiva (64.9%) and eyelids (24.5%). Lesions of the
      anterior segment were infrequent (9.1%) and those of the posterior segment were
      rare (1.5%). CONCLUSION: Ocular contusions account for a large part of ocular
      injuries in the ophthalmologic department of Cotonou National University Hospital
      and result above all from road traffic accidents. It is important to reduce the
      frequency in taking essentially preventive measures.

PMID- 20674083
TI  - [Treatment of circumscribed choroidal haemangiomas by photodynamic therapy: a
      review].
AB  - Circumscribed choroidal hemangioma (CCH) is an uncommon benign vascular tumor of
      the choroid that is usually diagnosed when it causes a decrease in vision due to
      exudative retinal detachment. The classical treatments of CCH were
      photocoagulation and radiotherapy, which induced additional chorioretinal damage,
      explaining the poor visual prognosis even in adequately treated patients. It is
      difficult to compare these two therapeutic options, laser photocoagulation having
      been abandoned for many years due to the retractile retinal scars that it
      induced. Conventional radiotherapy and proton therapy with a total dose of 20 Gy
      gave and give good results but can be performed only by teams used to these types
      of treatment. Recently, photodynamic therapy (PDT), which allows a selective
      occlusion of vascular lesions without damaging overlying retinal structures, has
      emerged as a sound alternative for the treatment of CCH. Most of the clinicians
      used the standard treatment of age related macular degeneration by photodynamic
      therapy (TAP) study protocol with or without variations. The main variations
      brought to the TAP study protocol were the duration of the verteporfin infusion,
      and/or the increase of the laser power settings, and/or the increase of the
      duration of exposure, and/or the number of PDT spots (single spot or multiple
      spots, overlapping or not). Mid-term PDT results are very encouraging. PDT has
      been reported to bring about resolution of subretinal fluid and to reduce tumor
      thickness in almost all cases. Visual acuity was improved or stabilized in at
      least 80% of the cases. Several studies reported on minor local side effects
      following PDT, consisting of atrophy and proliferation of the retinal pigment
      epithelium, atrophy of the choroid, transient choroidal effusion, and mild
      subretinal fibrosis. Published data demonstrated that PDT is a safe and effective
      alternative to radiotherapy or photocoagulation as first-line therapy for CCH.

PMID- 20674084
TI  - [Central toxic keratopathy and fibromyalgia: a case report].
AB  - INTRODUCTION: A patient with fibromyalgia after laser refractive surgery
      presented bilateral diffuse lamellar keratitis complicated by central toxic
      keratopathy. CLINICAL CASE: A 51-year-old patient, followed for fibromyalgia,
      consulted for visual loss 1 week after laser in situ keratomileusis. Slit lamp
      examination revealed stromal infiltrate in both eyes into the flap interface.
      Confocal microscopy showed an infiltration of inflammatory cells into the
      anterior stroma and the flap interface. Intensive topical corticosteroid
      treatment was used and the left eye was treated with flap lifting and interface
      irrigation. The corneal infiltrates decreased very slowly, and the left eye
      developed postoperative hyperopia. Diagnosis of central toxic keratopathy was
      discussed. Visual acuity, highly volatile, was limited to 7/10 (right eye) and
      6/10 (left eye). CONCLUSION: Diffuse lamellar keratitis (DLK) is a sterile
      inflammation after laser in situ keratomileusis. Central toxic keratopathy is
      characterized by noninflammatory central corneal opacification with a significant
      hyperopic shift. The cause of central toxic keratopathy is unknown. Fibromyalgia
      is a widespread, chronic pain disorder that includes a complex constellation of
      somatic and emotional symptoms. Patients often complain of dry eye sensations.
      Recent studies have highlighted a reduced corneal sensitivity in patients with
      fibromyalgia. There could be a relation between fibromyalgia, diffuse lamellar
      keratitis, and central toxic keratopathy. Some precautions may be used before
      LASIK in patients with fibromyalgia.

PMID- 20674085
TI  - "Pushed" monocanalicular intubation in children under general anesthesia with
      spontaneous ventilation. A preliminary report.
AB  - PURPOSE: We studied the possibility of placing a new type of monocanalicular
      nasal intubation under general anesthesia with spontaneous mask ventilation in
      congenital nasolacrimal duct obstruction. PATIENTS AND METHOD: This was a non
      randomized study of consecutive cases using a monocanalicular stent called the
      "pushed Monoka". The benefits of anchoring with meatus fixation are similar to
      the original Monoka device, but the probe guide or introducer is inside the
      silicone tube. The external diameter of the "pushed Monoka" is 0.96 mm (versus
      0.64 mm in the traditional Monoka). There are three lengths: 30, 35, and 40 mm.
      General anesthesia was administered by inhalation of a halogen gas using a facial
      mask. The technique was selected by lacrimal exploration to evaluate the extent
      of the stenosis (simple or complex). The location and freedom of movement of the
      stent into the inferior nasal meatus was tested using a second lacrimal probe.
      Only simple stenosis cases with positive metal-to-metal contact were included in
      the study. INSERTION TECHNIQUE: The introducer pushes the stent into the lacrimal
      duct. The introducer should be removed from the silicone sleeve very carefully by
      gently pulling it out, millimeter by millimeter. This action is carried out while
      paying careful attention to keeping the stent aligned with the major axis of the
      lacrimal sac. Throughout this phase, the anchoring plug should remain in contact
      with the lacrimal punctum. Once the introducer is completely removed, the
      anchoring plug is secured into the vertical canaliculus. A single-use plug
      inserter was used. RESULTS: Fourteen children (18 sides) with congenital
      nasolacrimal duct obstruction were consecutively included in the study. The
      pushed intubations were all performed under general anesthesia with spontaneous
      ventilation. The average age of the children was 26.2 months (range: 14 to 46
      months). The average duration of the procedure, measured between the moment that
      the facial mask was put into place and the child's awakening (crying,
      restlessness) was 14 minutes (range: 9 to 27 minutes). The most variable
      parameter was the use of the venous portal. The introduction of the pushed probe
      itself required an average 7 minutes (range: 3 to 11 minutes). None of the
      children showed epistaxis. In general terms, no intraoperative or postoperative
      complications were noted. The "pushed Monoka" tubes were withdrawn during
      postoperative appointments with a mean intubation duration of 34 days (range: 1
      to 59 days). Postoperative success (absence of epiphora, absence of mucous
      discharge) was achieved in 88% of cases (16/18 sides). The average follow-up was
      8.7 weeks (range: 3 to 26 weeks). Complications and side effects were minimal.
      One stent was withdrawn on day 1 due to a keratitis with respect to the anchoring
      plug. Three stents were spontaneously lost (16%) between day 2 and day 30.
      Anterior rhinoscopy found none of the stents in the inferior nasal meatus. These
      four cases were all considered successful as there was no postoperative epiphora
      noted. CONCLUSIONS: Pushed nasolacrimal intubation can be safely utilized under
      general anesthesia with spontaneous mask ventilation. This technique appears to
      be a simple and safe alternative to late and very late probing in the treatment
      of membranous congenital nasolacrimal duct obstruction in children older than 12
      months.

PMID- 20674086
TI  - [Xeroderma pigmentosum associated with intracerebral tumor: a case report].
AB  - Patients with the genetic disease xeroderma pigmentosum (XP) lack the ability to
      carry out a specific type of DNA repair process called nucleotide excision repair
      (NER). The NER pathway plays a critical role in the repair of DNA damage
      resulting from ultraviolet (UV) radiation. We report a case of a patient
      presenting a cutaneous form of XP. She presented acute paralysis of the third
      cranial nerve with cutaneous anesthesia. Nuclear magnetic resonance imaging
      revealed an intracranial tumor. She underwent surgery with incomplete tumor
      resection; anatomopathological study showed a schwannoma. Complementary
      radiosurgery was performed. The association between XP and neurological cancer is
      rare but not impossible. A priori, it would be assumed that the major medical
      outcome of hereditary deficiencies in DNA repair processes would be an increased
      risk of cancer. Indeed, there is an increased risk of cancer in several known DNA
      repair deficiencies including XP.

PMID- 20674087
TI  - Asymptomatic sustained ventricular fibrillation in a patient with left
      ventricular assist device.
AB  - Optimal medical treatment, cardiac resynchronization, and the use of an
      implantable cardioverter defibrillator are established therapies of severe
      congestive heart failure. In refractory cases, left ventricular assist devices
      are more and more used not only as bridging to cardiac transplantation but also
      as destination therapy. Ventricular arrhythmias may represent a life-threatening
      condition and often result in clinical deterioration in patients with congestive
      heart failure. We report a case of asymptomatic sustained ventricular
      fibrillation with preserved hemodynamics caused by a nonpulsatile left
      ventricular assist device. Consecutive adequate but unsuccessful discharges of
      the implantable cardioverter defibrillator were the only sign of the usually
      fatal arrhythmia, prompting the patient to consult emergency services.
      Electrolyte supplementation and initiation of therapy with amiodarone followed by
      external defibrillation resulted in successful restoration of a stable cardiac
      rhythm after 3.5 hours.

PMID- 20674088
TI  - The complexities of tracheal intubation with direct laryngoscopy and alternative
      intubation devices.
AB  - Intubation research on both direct laryngoscopy and alternative intubation
      devices has focused on laryngeal exposure and not the mechanics of actual
      endotracheal tube delivery or insertion. Although there are subtleties to
      tracheal intubation with direct laryngoscopy, the path of tube insertion and the
      direct line of sight are relatively congruent. With alternative intubation
      devices, this is not the case. Video or optical elements in alternative
      intubation devices permit looking around the curve of the tongue, without a
      direct line of sight to the glottic opening. With these devices, laryngeal
      exposure is generally the simple part of the procedure, and conversely, tube
      delivery to the glottic opening and advancement into the trachea are sometimes
      not straightforward. This article presents the mechanical and optical
      complexities of endotracheal tube insertion in both direct laryngoscopy and
      alternative devices. An understanding of these complexities is critical to
      facilitate rapid tracheal intubation and to minimize unsuccessful attempts.

PMID- 20674090
TI  - Prefrontal mediation of age differences in cognitive reappraisal.
AB  - Despite cognitive and physical declines, it has been suggested that older adults
      remain able to regulate their emotions effectively. However, whether this is true
      for all emotion regulation processes has not been established. We hypothesized
      that cognitive reappraisal, a form of emotion regulation requiring intact
      cognitive control ability, may be compromised in older age, and that this age
      difference would be mediated by reduced activation in prefrontal cortex (PFC).
      Sixteen younger and 15 older adults used gaze-directed reappraisal to increase
      and decrease emotion in response to unpleasant pictures. This was compared with
      simply viewing the pictures. Relative to younger adults, older adults were less
      successful using reappraisal to decrease unpleasant emotion but more successful
      using reappraisal to increase unpleasant emotion. They also exhibited reduced
      activation in dorsomedial and left ventrolateral prefrontal cortex. Importantly,
      activation in these regions differentially mediated the effect of age on emotion.
      This pattern confirms the importance of cognitive control in reappraising
      unpleasant situations and suggests that older age may (but does not always)
      confer effective emotion regulation.

PMID- 20674091
TI  - Estrogen receptor alpha gene variants are associated with Alzheimer's disease.
AB  - The present research is aimed at assessing the role of 3 estrogen receptor alpha
      (ESR1) gene variants in late onset Alzheimer's disease (AD) susceptibility. One
      thousand one hundred thirteen unrelated late onset sporadic AD patients, 1109
      healthy controls and 121 neurologically healthy elderly controls were used to
      carry out case-control genetic association studies with ESR1 rs3844508,
      rs2234693, and ESR1 noncoding deletion 1 (ESR1-NCD1) polymorphisms. Thirty-five
      healthy male samples were used for molecular analyses. The rs2234693 polymorphism
      is associated with AD in our population (odds ratio [OR], 1.29; p = 0.008). The
      rs3844508 marker confers protection against AD in males (OR, 0.57; p = 0.001) and
      the deletion ESR1-NCD1 is a risk factor for AD in women (OR, 1.67; p < 0.001).
      Molecular analyses on ESR1-NCD1 indicate that this deletion confers a higher
      response to estradiol activity on ESR1 receptor and it is also associated with
      differential expression of ESR1 isoforms. Our results support the involvement of
      ESR1 gene in AD and point to the existence of sexual dimorphism for ESR1 markers.
      In addition, carriers of ESR1-NCD1 deletion could overrespond to estradiol
      action.

PMID- 20674092
TI  - HSV-1 promotes Ca2+ -mediated APP phosphorylation and Abeta accumulation in rat
      cortical neurons.
AB  - Epidemiological and experimental findings suggest that chronic infection with
      Herpes simplex virus type 1 (HSV-1) may be a risk factor for Alzheimer's disease
      (AD), but the molecular mechanisms underlying this association have not been
      fully identified. We investigated the effects of HSV-1 on excitability and
      intracellular calcium signaling in rat cortical neurons and the impact of these
      effects on amyloid precursor protein (APP) processing and the production of
      amyloid-beta peptide (Abeta). Membrane depolarization triggering firing rate
      increases was observed shortly after neurons were challenged with HSV-1 and was
      still evident 12 hours postinfection. These effects depended on persistent sodium
      current activation and potassium current inhibition. The virally induced
      hyperexcitability triggered intracellular Ca(2+) signals that significantly
      increased intraneuronal Ca(2+) levels. It also enhanced activity- and Ca(2+)
      dependent APP phosphorylation and intracellular accumulation of Abeta42. These
      findings indicate that HSV-1 causes functional changes in cortical neurons that
      promote APP processing and Abeta production, and they are compatible with the co
      factorial role for HSV-1 in the pathogenesis of AD suggested by previous
      findings.

PMID- 20674094
TI  - Aluminum induces neurodegeneration and its toxicity arises from increased iron
      accumulation and reactive oxygen species (ROS) production.
AB  - The neurotoxicity of aluminum (Al) - the most abundant metal element on earth -
      has been known for years. However, the mechanism of Al-induced neurodegeneration
      and its relationship to Alzheimer's disease are still controversial. In
      particular, in vivo functional data are lacking. In a Drosophila model with
      chronic dietary Al overloading, general neurodegeneration and several behavioral
      changes were observed. Al-induced neurodegeneration is independent of beta
      amyloid or tau-associated toxicity, suggesting they act in different molecular
      pathways. Interestingly, Drosophila frataxin (dfh), which causes Friedreich's
      ataxia if mutated in humans, displayed an interacting effect with Al, suggesting
      Friedreich's ataxia patients might be more susceptible to Al toxicity. Al-treated
      flies accumulated large amount of iron and reactive oxygen species (ROS), and
      exhibited elevated SOD2 activity. Genetic and pharmacological efforts to reduce
      ROS or chelate excess Fe significantly mitigated Al toxicity. Our results
      indicate that Al toxicity is mediated through ROS production and iron
      accumulation and suggest a remedial route to reduce toxicity due to Al exposure.

PMID- 20674093
TI  - Nuclear localization sequence of FUS and induction of stress granules by ALS
      mutants.
AB  - Mutations in fused in sarcoma (FUS) have been reported to cause a subset of
      familial amyotrophic lateral sclerosis (ALS) cases. Wild-type FUS is mostly
      localized in the nuclei of neurons, but the ALS mutants are partly mislocalized
      in the cytoplasm and can form inclusions. We demonstrate that the C-terminal 32
      amino acid residues of FUS constitute an effective nuclear localization sequence
      (NLS) as it targeted beta-galactosidase (LacZ, 116 kDa) to the nucleus. Deletion
      of or the ALS mutations within the NLS caused cytoplasmic mislocalization of FUS.
      Moreover, we identified the poly-A binding protein (PABP1), a stress granule
      marker, as an interacting partner of FUS. Large PABP1-positive cytoplasmic foci
      (i.e. stress granules) colocalized with the mutant FUS inclusions but were absent
      in wild-type FUS-expressing cells. Processing bodies, which are functionally
      related to stress granules, were adjacent to but not colocalized with the mutant
      FUS inclusions. Our results suggest that the ALS mutations in FUS NLS can impair
      FUS nuclear localization, induce cytoplasmic inclusions and stress granules, and
      potentially perturb RNA metabolism.

PMID- 20674095
TI  - BDNF upregulation rescues synaptic plasticity in middle-aged ovariectomized rats.
AB  - Brain-derived neurotrophic factor (BDNF) has emerged as a possible broad-spectrum
      treatment for the plasticity losses found in rodent models of human conditions
      associated with memory and cognitive deficits. We have tested this strategy in
      the particular case of ovariectomy. The actin polymerization in spines normally
      found after patterned afferent stimulation was greatly reduced, along with the
      stabilization of long-term potentiation, in hippocampal slices prepared from
      middle-aged ovariectomized rats. Both effects were fully restored by a 60-minute
      infusion of 2 nM BDNF. Comparable rescue results were obtained after elevating
      endogenous BDNF protein levels in hippocampus with 4 daily injections of a short
      half-life ampakine (positive modulator of alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionate [AMPA]-type glutamate receptors). These results provide the
      first evidence that minimally invasive, mechanism-based drug treatments can
      ameliorate defects in spine plasticity caused by depressed estrogen levels.

PMID- 20674096
TI  - Engulfment adapter PTB domain containing 1 interacts with and affects processing
      of the amyloid-beta precursor protein.
AB  - Previous studies identified engulfment adapter phosphotyrosine binding (PTB)
      domain containing 1 (GULP1) as an NPXY-motif interactor of low-density
      lipoprotein receptor-related protein 1 (LRP1) and suggested a potential relevance
      in Alzheimer's disease (AD). Since AD associated proteins amyloid-beta A4
      precursor protein (APP) and LRP1 were shown to interact with the PTB domain of
      Fe65 and several other adapters via their intracellular NPXY-motifs, we examined
      a possible interaction of GULP1 PTB domain with the YENPTY-motif of APP. Here we
      demonstrate that GULP1 is present in human hippocampal and neocortical neurons.
      Confocal live cell imaging revealed that coexpressed and endogenous GULP1
      colocalizes with APP in the Golgi and endoplasmic reticulum. Analysis of the
      interacting domains by co-immunoprecipitation of point and deletion mutants
      revealed that the interaction depends on the PTB domain of GULP1 and the YENPTY
      motif of APP. Coexpression of GULP1 affected APP cell surface localization and
      suppressed generation of Abeta40/42 and sAPPalpha. Taken together, these data
      identify GULP1 as a novel neuronal APP interacting protein that alters
      trafficking and processing of APP.

PMID- 20674097
TI  - Rectal bleeding and diarrhea caused by bortezomib-induced colitis.

PMID- 20674098
TI  - [Evaluation of a new latex agglutination test for serotyping of Streptococcus
      pneumoniae strains covered by the 7-valent conjugate vaccine].

PMID- 20674099
TI  - Inhibition of monoamine oxidase by indole and benzofuran derivatives.
AB  - Monoamine oxidase (MAO) is an important drug target for the treatment of
      neurological disorders. A series of indole and benzofuran derivatives were
      synthesised and evaluated as inhibitors of the two MAO isoforms, MAO-A and MAO-B.
      In general, the derivatives were found to be selective MAO-B inhibitors with K(i)
      values in the nanoMolar (nM) to microMolar (microM) concentration range. The most
      potent MAO-B inhibitor, 3,4-dichloro-N-(2-methyl-1H-indol-5-yl)benzamide,
      exhibited a K(i) value of 0.03 microM and was 99 fold more selective for the B
      isoform. We conclude that these indole and benzofuran derivatives are promising
      reversible MAO-B inhibitors with a possible role in the treatment of
      neurodegenerative diseases such as Parkinson's disease (PD).

PMID- 20674100
TI  - [Asymmetrical lungs].

PMID- 20674101
TI  - [Persistent neurological disturbances].

PMID- 20674102
TI  - [Pulmonary arterial hypertension and malignant hematologic disorders].
AB  - Many recent publications have evidenced a statistical link between pulmonary
      arterial hypertension and myeloproliferative disorders, once excluded secondary
      causes of pulmonary arterial hypertension (more particularly, portal hypertension
      or thromboembolic events). Nonetheless, the frequency of such an association is
      quite variable, from 10 to 50 % and depends both on the population studied and on
      the type of myeloproliferative disorder. The most robust association is observed
      with essential thrombocythemia. Pulmonary arterial hypertension has also been
      described in association with lymphoma, acute leukemia, myeloma or large granular
      lymphocyte proliferation. The absence of large series call for a prospective
      study of pulmonary arterial hypertension in malignant hematologic disorders to
      firmly establish the exact frequency of such an association, to define more
      precisely its physiopathology in order to elaborate more specific diagnostic
      criteria together with guidelines for both treatment and follow-up.

PMID- 20674103
TI  - [Autoimmune hepatitis: diagnostic and therapeutic up-to-date].
AB  - Autoimmune hepatitis is a disorder of unknown aetiology that occurs in children
      and adults of all ages with a female predominance. The spectrum of presentation
      is wide, ranging from no symptoms to acute liver failure. The diagnosis is based
      on high level serum gammaglobulins, characteristic circulating autoantibodies and
      histologic abnormalities (necrosis and inflammation). Autoimmune hepatitis is
      classified on the basis of the autoantibody pattern: type 1 (antinuclear and/or
      smooth muscle antibodies) is the classic form whereas type II (liver-kidney
      microsome 1 antibody) is much less common and occurs mainly in childhood. Mixed
      forms of autoimmune hepatitis that share features with other putative autoimmune
      liver diseases, primary biliary cirrhosis and primary sclerosing cholangitis,
      have been described. Because of therapeutic issues, it is important to
      distinguish autoimmune hepatitis from other forms of hepatitis and the use of
      diagnostic scoring systems may be helpful. The treatment of autoimmune hepatitis
      has not changed for the past 30 years. It consists of corticosteroids associated
      with azathioprine. This treatment is rapidly effective but usually only
      suspensive. Relapse after treatment withdrawal is the rule (80% of cases). The
      main risk factor of recurrence is the degree of residual inflammation on liver
      biopsy. The frequency of side effects justifies an attempt of drug
      discontinuation provided that criteria of clinical, biochemical and histological
      remission are achieved after at least 2 years of treatment.

PMID- 20674104
TI  - [Rifampin-induced severe aseptic meningitis].
AB  - We report the first case of acute drug-induced aseptic meningitis (DIAM) due to
      rifampin in a young female with systemic lupus erythematosus (SLE). DIAM is
      uncommon and its diagnosis is often difficult. This type of drug hypersensitivity
      is more frequently observed in patients with a history of auto-immune disease,
      particularly SLE. The major categories of causative agents are: nonsteroidal anti
      inflammatory drugs, antimicrobials, intravenous immunoglobulins and biotherapies.

PMID- 20674105
TI  - [Endocrine hypertension].
AB  - Endocrine hypertension represents more than half of the causes of secondary
      hypertension. This entity encompasses several diseases including primary
      aldosteronism, paraganglioma/pheochromocytoma and Cushing's syndrome. The
      screening of endocrine hypertension should be performed in all the patients
      presenting with: (1) a resistant hypertension; (2) a severe hypertension; (3) the
      coexistence of hypertension with an adrenal adenoma, clinical or biological
      abnormalities. Clinical signs and symptoms, whenever present, lack specificity,
      especially for primary aldosteronism where hypertension is usually the unique
      symptom. Screening is performed by the measurement of several hormones and by a
      tomodensitometry to study the morphology of the adrenals: the presence of a
      solitary or multiples adenomas, or hyperplasia. Pheochromocytoma and Cushing's
      syndrome are very uncommon and should be referred to specialized centres. Primary
      aldosteronism is a frequent cause of secondary hypertension. Once the diagnosis
      is obtained, it is essential to differentiate whether it is a surgically
      correctable form or not. The patients with a bilateral adrenal hyperplasia can be
      managed effectively by mineralocorticoids receptor antagonist. The adrenalectomy
      will cure or improve hypertension for the majority of the patients with a
      lateralized secretion of aldosterone. The diagnosis and the treatment of these
      disorders can be challenging. However, the diagnosis of endocrine hypertension
      allows diagnosing surgical correctable form of hypertension, which is not
      possible in essential hypertension.

PMID- 20674106
TI  - Involved surgical margins in oral and oropharyngeal carcinoma-an anatomical
      problem?
AB  - A previous audit conducted in the West of Scotland (WoS) suggested that
      anatomical factors accounted for a substantial proportion of invaded surgical
      margins after resection of an oral or oropharyngeal squamous cell carcinoma
      (SCC). Since then a number of technical improvements have taken place, the most
      important of which has been advanced digital imaging that has enabled better
      surgical planning. In this study we compare the incidence of involved surgical
      margins in a recent group with those found in the earlier audit. The earlier
      (WoS) group comprised a consecutive series of patient operated on for a primary
      SCC of the oral cavity or oropharynx between November 1999 and November 2001
      (n=296). The later series comprised 178 patients operated on for oral or
      oropharyngeal SCC at the Southern General Hospital (SGH), Glasgow, between 2006
      and 2009. A total of 245 patients in the WoS cohort had information available on
      the invasion of the margins of whom 68 (28%) had an invaded margin. Of 177
      patients in the SGH group, 9 (5%) had an invaded margin (p=0.001). An anatomical
      approach to the resection of oral and oropharyngeal SCC is appropriate, as it
      results in a rate of invaded margins of less than 10% irrespective of size and
      site of the primary lesion.

PMID- 20674107
TI  - Reasons for delayed presentation in oral and oropharyngeal cancer: the patients
      perspective.
AB  - Patients with oral and oropharyngeal cancer (OOC) often delay presenting to their
      doctor or dentist. The aims of this study were to ask a consecutive cohort
      following treatment for OOC about their initial symptoms and the time spent
      before presentation to the healthcare profession. Also to discover their views on
      how to reduce delays in presentation. From a 2-year cohort treated within 2
      years, 71 completed a short survey and 44 were subsequently interviewed by
      telephone. A non-healing ulcer or sore was the commonest symptom patients first
      related to having cancer. Around half interpreted their symptoms as something
      minor, staying much the same initially, and something that probably would get
      better by itself. Most would have sought advice earlier if they had been more
      aware of oral cancer. Although many patients talked about their symptoms to
      spouse, partner, family or friends, over one-third said they spoke to nobody
      about it. Our sample did not find that access to a doctor or a dentist was a
      barrier to seeking advice. This study highlights that from the patients
      perception they generally thought their symptoms were trivial, would get better
      by themselves and gave little thought as to whether it might be cancer. Patients
      commented they knew nothing more about the disease. In their views the best way
      to get patients to self refer earlier was through improved awareness of the
      disease, as many felt there was a gross lack of knowledge in this field of
      cancers compared to other cancers.

PMID- 20674108
TI  - Management of vascular lesions of the mouth and lips using a potassium titanyl
      phosphate (KTP) laser: review of patient satisfaction.
AB  - We reviewed patient satisfaction with the management of oral vascular lesions
      using a potassium titanyl phosphate (KTP) laser. Questionnaires consisting of 10
      questions were given to 95 patients who had had laser treatment for oral vascular
      lesions between September 2007 and July 2009. A five-point scale ranging from
      poor (1) to very good (5) was used for the responses. Seventy-one percent of
      patients responded. Overall, they were very satisfied with the process of laser
      treatment (mean score more than 4.5/5), but were less satisfied with the levels
      of comfort 24h after the procedure (mean score 3.7/5), and after one week (mean
      score 4.2/5). As postoperative discomfort was highlighted as an area of
      dissatisfaction for some patients, modifications to aftercare instructions may
      improve this aspect of the service.

PMID- 20674109
TI  - Patient and carer unmet needs: a survey of the British association of head and
      neck oncology nurses.
AB  - The aim of this survey was to ask members of the British Association of Head and
      Neck Oncology Nurses (BAHNON) about the identification of patients and carers
      unmet needs in the routine out-patient review clinic and the support services
      available during consultation. A national postal survey was sent out to the 210
      current members of BAHNON in November 2009. Reminders were sent to non-responders
      in February 2010. The response rate was 61% (129/210). The vast majority (80%)
      were Clinical Nurse Specialists (CNS). The questionnaire data support the strong
      belief in attempts to identify unmet needs with over three-quarters feeling
      strongly about themselves being personally involved in attempting to identify
      unmet needs. Most of the responders used counselling and communication methods to
      elicit unmet concerns rather than specific tools such as questionnaires. The vast
      majority clearly felt that identifying unmet needs in clinic improves patients'
      perception of outcome post-treatment. Support services' readily' available at the
      time of consultation were as follows: H&N CNS (99%), Speech and Language (86%),
      Oncologist (84%), Dietician/Nutritionist (84%), Dentist (44%), Oral
      Rehabilitation consultant (27%), Dental Hygienist (26%), Physiotherapist (21%),
      Chaplain (20%), Emotional Support therapist (15%), Psychologist (15%),
      Occupational therapist (13%), Social worker (8%), other (11%). Although
      responders felt it very important to identify unmet needs in follow-up clinics,
      there is reliance on one to one discussion with the patient and carer. Hence in a
      busy clinic, needs might be easily missed and further research is required into
      ways to facilitate their identification.

PMID- 20674110
TI  - Direct and indirect effects of ammonia, ammonium and nitrate on phosphatase
      activity and carbon fluxes from decomposing litter in peatland.
AB  - Here we investigate the response of soils and litter to 5 years of experimental
      additions of ammonium (NH4), nitrate (NO3), and ammonia (NH3) to an ombrotrophic
      peatland. We test the importance of direct (via soil) and indirect (via litter)
      effects on phosphatase activity and efflux of CO2. We also determined how species
      representing different functional types responded to the nitrogen treatments. Our
      results demonstrate that additions of NO3, NH4 and NH3 all stimulated phosphatase
      activity but the effects were dependent on species of litter and mechanism
      (direct or indirect). Deposition of NH3 had no effect on efflux of CO2 from
      Calluna vulgaris litter, despite it showing signs of stress in the field, whereas
      both NO3 and NH4 reduced CO2 fluxes. Our results show that the collective impacts
      on peatlands of the three principal forms of nitrogen in atmospheric deposition
      are a result of differential effects and mechanisms on individual components.

PMID- 20674111
TI  - Effects of iron(III)chelates on the solubility of heavy metals in calcareous
      soils.
AB  - In this study I evaluated the effects of complexing agents on the solubility of
      heavy metals in an incubation experiment up to 56 days when complexing agents
      were applied as Fe-chelates (Fe-EDDS(S,S), Fe-EDDS(mix), Fe-EDTA and Fe-EDDHA) on
      calcareous soils at a level sufficient to correct Fe chlorosis (0.1 mmol kg(-1)).
      Of these ligands, EDDHA was the most efficient in keeping Fe in water-soluble
      form, and EDDS increased the solubility of Cu and Zn most, and only EDTA
      increased the solubility of Cd and Pb. EDTA increased the solubility of Ni
      steadily during the incubation period, equalling about 5-8% of the added EDTA
      concentration. [S,S]-EDDS was biodegraded within 56 days, whereas EDDS(mix) was
      less biodegradable. Ni-chelates were the most recalcitrant against
      biodegradation. The study shows that even a moderate input of chelates to soil
      increases the solubility of toxic heavy metals and their risk of leaching.

PMID- 20674112
TI  - Mosses as biomonitors of atmospheric heavy metal deposition: spatial patterns and
      temporal trends in Europe.
AB  - In recent decades, mosses have been used successfully as biomonitors of
      atmospheric deposition of heavy metals. Since 1990, the European moss survey has
      been repeated at five-yearly intervals. Although spatial patterns were metal
      specific, in 2005 the lowest concentrations of metals in mosses were generally
      found in Scandinavia, the Baltic States and northern parts of the UK; the highest
      concentrations were generally found in Belgium and south-eastern Europe. The
      recent decline in emission and subsequent deposition of heavy metals across
      Europe has resulted in a decrease in the heavy metal concentration in mosses for
      the majority of metals. Since 1990, the concentration in mosses has declined the
      most for arsenic, cadmium, iron, lead and vanadium (52-72%), followed by copper,
      nickel and zinc (20-30%), with no significant reduction being observed for
      mercury (12% since 1995) and chromium (2%). However, temporal trends were country
      specific with sometimes increases being found.

PMID- 20674113
TI  - Medication adherence behavior and priorities among older adults with CKD: a
      semistructured interview study.
AB  - BACKGROUND: Older adults with chronic kidney disease (CKD) typically use more
      than 5 medications and have multiple prescribing physicians. However, little is
      known about how they prioritize their medical conditions or decide which
      medications to take. METHODS: Semistructured interviews (average length, 40
      minutes) with 20 community-dwelling adults with CKD stages 3-5D receiving
      nephrology care at a tertiary referral center. Respondents were asked about
      medications, prescribing physicians, and medication-taking behaviors. We
      performed thematic analysis to explain patients' decisions regarding medication
      prioritization, understanding, and adherence decisions. RESULTS: Participants
      (age range, 55-84 years; mean, 72 years) used 5-14 prescribed medications, had 2
      9 physicians, and had 5-11 comorbid conditions. All had assigned implicit
      priorities to their medications. Although most expressed the intention to be
      adherent, many regularly skipped medications they considered less important. Most
      identified the prescribing physician and indication for each medication, but
      there often was substantial discordance between beliefs about medications and
      conventional medical opinion. Respondents prioritized medications based on the
      salience of the particular condition, perceived effects of the treatment, and
      barriers (physical, logistic, or financial) to using the prescribed drug. Side
      effects of medications were common and anxiety provoking, but discussions with
      the prescribing physician often were delayed or unfulfilling for the patient.
      CONCLUSIONS: Polypharmacy in patients with CKD leads to complex medication
      choices and adherence behaviors in this population. Most patients we interviewed
      had beliefs or priorities that were nonconcordant with conventional medical
      opinion; however, patients rarely discussed these beliefs and priorities or the
      resultant poor medication adherence with their physicians. Further study is
      needed to provide quantitative data about the magnitude of adherence barriers. It
      is likely that more effective communication about medication use could improve
      patients' health outcomes and reduce potential adverse drug events.

PMID- 20674114
TI  - Measuring the impact of programs that challenge the public stigma of mental
      illness.
AB  - Public stigma robs people with mental illnesses from rightful opportunities
      related to work and other important life goals. Advocates have developed anti
      stigma programs meant to address the prejudice and discrimination associated with
      these conditions. Evidence is now needed to make sense of program impact; this
      paper looks at measurement issues related to stigma change. Community-based
      participatory research is central to this research and includes the involvement
      of a diverse collection of stakeholders in all phases of evaluation.
      Investigators should be cautious about measures vis-a-vis social desirability
      effects and should directed by social validity of targeted audiences. Conceptual
      domains with some research support that correspond with assessments include
      behavior, penetration, psychological perspective, knowledge, and
      physiological/information processes. These issues are summarized as ten
      recommendations for evaluation of anti-stigma programs.

PMID- 20674115
TI  - Assisting war-torn populations--should we prioritize reducing daily stressors to
      improve mental health? Comment on Miller and Rasmussen (2010).

PMID- 20674116
TI  - Exploring the use of social network methods in designing healthcare quality
      improvement teams.
AB  - Teams are an integral component of quality improvement efforts in healthcare
      organizations. Quality improvement teams may involve persons either from the same
      or different disciplines. In either case, the selection of team members may be
      critical to the team's success. However, there is little research to guide
      selection of team members for quality improvement teams. In this paper, we use
      tools from social network analysis (SNA) to derive principles for the design of
      effective clinical quality improvement teams and explore the implementation of
      these principles using social network data collected from the inpatient general
      medicine services at a large academic medical center in Chicago, USA. While the
      concept of multidisciplinary teams focuses on the importance of the professional
      background of team members, SNA emphasizes the importance of the individual and
      collective connections of team members, both to persons outside the team and to
      each other. SNA also focuses on the location of individuals and groups between
      other actors in the flow of information and other resources within larger
      organizational networks. We hypothesize that external connections may be most
      important when the collection or dissemination of information or influence are
      the greatest concerns, while the relationship of team members to each other may
      matter most when internal coordination, knowledge sharing, and within-group
      communication are most important. Our data suggest that the social networks of
      the attending physicians can be characterized sociometrically and that new
      sociometric measures such as "net degree" may be useful in identifying teams with
      the greatest potential for external influence.

PMID- 20674117
TI  - Associations between income inequality at municipality level and health depend on
      context - a multilevel analysis on myocardial infarction in Sweden.
AB  - This study investigates whether a) income inequality in Swedish municipalities
      increases the risk of myocardial infarction (AMI); b) the association between
      income inequality and AMI is mediated by level of residential segregation,
      measured as homogeneity in parishes (as a proxy for neighbourhoods) within
      municipalities; and c) there is an interaction between parish homogeneity and
      individual level social position. The study population consisted of all
      individuals aged 40-64 years in 1990 who lived in municipalities with >50,000
      inhabitants (n = 1,284,955). Data on socioeconomic, demographic information and
      diagnosis data on AMI were obtained by linkage between authority-administered
      registers and the National Patient Register. All individuals were followed from
      1991 onwards until the first relevant discharge, death or end of observation
      period (1998). We used a multilevel Poisson model where individuals were nested
      within 729 parishes which in turn were nested in 41 municipalities. We found that
      the risk for AMI was lower in the municipalities with higher degree of income
      inequality. Segregation of households in the highest income quintile diluted, but
      did not eliminate, the association between income inequality and risk of AMI -
      the degree of parish affluence seemed to be more important as a mediator than
      other parish characteristics, even when individual level characteristics were
      added to the model. Interaction analyses showed that the divide between manual
      workers and non-manual employees became more apparent in parishes with a higher
      degree of parish affluence. This was more apparent in municipalities with higher
      income inequality and was due to a decreasing risk among high level non-manual
      employees and an unchanged risk among manual workers. The results give some
      support to the idea that income inequality might serve as a proxy for social
      stratification even in a comparatively egalitarian context.

PMID- 20674118
TI  - Medical specialty prestige and lifestyle preferences for medical students.
AB  - In the context of doctor shortages and mal-distributions in many Western
      countries, prestige and lifestyle friendliness have emerged as significant
      factors for medical students when they choose a medical specialty. In this study,
      we surveyed two samples of Australian medical students and had them rank 19
      medical specialties for prestige (N = 530) and lifestyle friendliness (N = 644).
      The prestige rankings were generally consistent with previous ratings by
      physicians, lay people and advanced medical students, with surgery, internal, and
      intensive care medicine ranking the highest, and public health, occupational, and
      non-specialist hospital medicine ranking lowest. This suggests that medical
      students have incorporated prevailing prestige perceptions of practicing doctors
      and the community. Lifestyle rankings were markedly different from prestige
      rankings, where dermatology, general practice, and public health medicine were
      ranked the most lifestyle friendly, and surgery, obstetrics/gynaecology and
      intensive care were ranked least friendly. Student lifestyle rankings differed
      from physician and author-generated rankings, indicating that student preferences
      should be considered rather than relying on ratings created by others. Few
      differences were found for gender or year of study, signifying perceptions of
      prestige and lifestyle friendliness were consistent across the students sampled.
      Having access to and understanding these rankings will assist career counsellors
      to aid student and junior doctor decision-making and aid workforce planners to
      address gaps in medical specialty health services.

PMID- 20674119
TI  - Mycobacterium lentiflavum--a cause of infections in the head and neck: case
      report and literature review.

PMID- 20674120
TI  - Evaluation for clinical predictors of positive temporal artery biopsy in giant
      cell arteritis.
AB  - PURPOSE: To examine the clinical predictors of a positive temporal artery biopsy
      (TAB) among patients suspected of having giant cell arteritis. PATIENTS AND
      METHODS: We conducted a retrospective study of all consecutive patients who
      underwent TAB by a single surgeon (K.L.R.) at the Department of Oral
      Maxillofacial Surgery from April 30, 2002, to June 29, 2006. The medical records
      were reviewed for the clinical symptoms, laboratory findings, biopsy results, and
      final diagnosis. The variables of interest as predictors of positive biopsy
      findings were analyzed using logistic regression analysis. RESULTS: During the
      study period, 82 patients underwent TAB. Histologic evidence of arteritis was
      present in 22 patients (26.8%). Two (2.4%) were diagnosed with giant cell
      arteritis clinically but had negative TAB findings. The patients presenting with
      weight loss or jaw claudication were more likely to have a positive TAB finding
      (odds ratio 4.50, 95% confidence interval 1.45 to 13.93; and odds ratio 3.71, 95%
      confidence interval 1.28 to 10.76, respectively). No laboratory findings were
      predictive of a positive TAB finding. Prednisone use before TAB also was not
      associated with a decreased likelihood of a positive finding. CONCLUSIONS:
      Patients suspected of having giant cell arteritis were more likely to have a
      positive TAB finding if they presented with weight loss or jaw claudication. In
      the present series, corticosteroid therapy before biopsy did not affect the rate
      of positive TAB findings.

PMID- 20674121
TI  - Bone healing after bur and Er:YAG laser ostectomies.
AB  - PURPOSE: Ostectomies, performed by different methods, are often necessary in oral
      and maxillofacial surgery. Rotatory and reciprocating devices are most frequently
      used but have disadvantages, such as noise, vibration, and the potential for
      inducing thermal damage. Laser systems are interesting alternatives to these
      procedures. We analyzed bone healing in a rat model after mandibular ostectomy
      with a surgical bur or noncontact erbium:yttrium-aluminum-garnet laser using
      different energy levels. MATERIALS AND METHODS: Four groups of 5 rats each
      underwent ostectomy of the bone cortical of the mandibular body, with irrigation,
      using a surgical bur or erbium:yttrium-aluminum-garnet laser with different
      energy parameters. A metal plate was used for morphologic standardization of the
      cavities. The samples collected after 7, 14, 45, 60, and 90 days were analyzed by
      optical microscopy. RESULTS: The ostectomies performed with surgical burs
      resulted in bone healing from the cortical endosteum and remaining trabecular
      bone. The cortical endosteum was repaired after 45 days, followed by bone
      remodeling. After laser irradiation, healing involved bone neoformation from the
      external cortical surface and endosteum. Surface regions with thermal damage were
      observed after laser treatment in the 3 conditions used up to day 60, followed by
      bone remodeling. CONCLUSIONS: Laser ostectomies resulted in a thin layer of
      thermal damage. Bone healing was faster when surgical burs were used, with
      similar results reached after 90 days.

PMID- 20674123
TI  - Surgical and prosthodontic consequences of inadequate treatment planning for
      fixed implant-supported prosthesis in the edentulous mandible.
AB  - Treatment planning for mandibular fixed implant-supported prostheses requires
      close communication between surgeons and restorative dentists. Improper implant
      positioning can result in significant difficulty for patient comfort and
      fabrication of a functional prosthesis. This case report describes the
      consequences of placing implants with no preoperative planning with regard to the
      implant position based on the final restorative plan. A 46-year-old male had all
      of his remaining maxillary and mandibular teeth extracted, and had 5 implants
      placed immediately in the interforaminal region of the mandible with the intent
      of providing a fixed prosthesis. Six weeks later, the patient was referred for
      prosthodontic care. The patient had no prostheses at that time and was in severe
      pain due to impingement of the lower lip by one of the implants. The implants
      were deemed to be in unfavorable positions and angulations. Thereafter, the case
      was treatment-planned systematically, requiring 2 additional surgical procedures-
      -removal of one of the implants and alveoloplasty of posterior mandible for
      creation of space for prosthetic components. The remaining 4 implants with
      unfavorable angulations posed a prosthodontic challenge for fabrication of a
      prosthesis. The situation was eventually managed by fabrication of a screw
      retained metal-resin fixed prosthesis over the remaining 4 implants. Although the
      situation was managed successfully, it resulted in increased time and treatment
      expenses, additional appointments, and elaborative steps for correction.
      Prosthodontics-driven treatment planning concepts and guidelines for prevention
      of such situations are described in this article.

PMID- 20674122
TI  - In vitro oral biofilm formation on triclosan-coated sutures in the absence and
      presence of additional antiplaque treatment.
AB  - PURPOSE: This study evaluated the in vitro plaque inhibitory effect of triclosan
      coated polyglactin 910 sutures in the absence and presence of an additional
      antiplaque agent commonly used after oral surgery. MATERIALS AND METHODS:
      Triclosan-coated sutures were incubated for 4 hours in freshly collected human
      saliva and, when appropriate, subsequently treated with an antiplaque rinse
      containing chlorhexidine-cetyl pyridinium as active components. Sutures without a
      triclosan-coating served as a control. RESULTS: Triclosan-coated sutures harbored
      similar amounts of plaque as did uncoated sutures. Exposure to the antiplaque
      rinse caused significant decreases in viable organisms for uncoated and triclosan
      coated sutures. However, after application of the antiplaque rinse, more micro
      organisms were found on triclosan-coated than on uncoated sutures. CONCLUSION:
      Sutures coated with triclosan do not provide a sufficient antimicrobial effect to
      prevent in vitro colonization by oral bacteria, whereas use in combination with a
      chlorhexidine-cetyl pyridinium-containing antiplaque rinse appears to be
      counterproductive.

PMID- 20674124
TI  - Effects of Class III malocclusion on young male adults' vocal tract development:
      a pilot study.
AB  - PURPOSE: To compare the vocal tract configuration between male speakers with
      Class III malocclusion and their normally developing counterparts and to
      investigate the concomitant acoustic changes caused by the alterations in vocal
      tract configuration. PATIENTS AND METHODS: Eight young male patients with Class
      III malocclusion and 8 normally developing counterparts participated in this
      study. Acoustic reflection technology was used to measure vocal tract dimensions
      in the 2 groups. A continuous speech sample and 4 sustained vowels (/a/, /ae/,
      /i/, and /u/) were recorded from each participant to obtain the fundamental
      frequency and the first 3 formant frequencies (F1, F2, and F3). RESULTS: The
      results showed significantly greater oral length and oral volume for young male
      patients with Class III malocclusion than their cohorts. The F1 of vowel /u/ was
      found to be significantly higher in male patients with Class III malocclusion
      than their cohorts. The vowel space of the 4 recorded vowels was reduced and the
      F1-F2 formant map for /u/ was relatively more scattered in male patients with
      Class III malocclusion than in the control speakers. CONCLUSION: This study has
      provided preliminary information on the effects of Class III malocclusion on
      vocal tract configuration and concomitant acoustic changes in young male
      patients.

PMID- 20674125
TI  - Shrapnel-induced mandibular hypomobility.

PMID- 20674126
TI  - Laryngeal mask airways have a lower risk of airway complications compared with
      endotracheal intubation: a systematic review.
AB  - PURPOSE: The purpose of the present study was to determine whether, in patients
      undergoing general anesthesia, those provided with a laryngeal mask airway (LMA)
      have a lower risk of airway-related complications than those undergoing
      endotracheal intubation. MATERIALS AND METHODS: A systematic review of randomized
      prospective controlled trials was done to compare the risk of airway
      complications with an LMA versus an endotracheal tube (ETT) in patients receiving
      general anesthesia. Two independent reviewers identified 29 randomized
      prospective controlled trials that met the predetermined inclusion and exclusion
      criteria. The data for each individual outcome measure were combined to analyze
      the relative risk ratios (RRs). The Cochrane RevMan software was used for
      statistical analysis. RESULTS: When an ETT was used to protect the airway, a
      statistically significant greater incidence of hoarse voice (RR 2.59, 95%
      confidence interval [CI] 1.55 to 4.34), a greater incidence of laryngospasm
      during emergence (RR 3.16, 95% CI 1.38 to 7.21), a greater incidence of coughing
      (RR 7.12, 95% CI 4.28 to 11.84), and a greater incidence of sore throat (RR 1.67,
      95% CI 1.33 to 2.11) was found compared with when an LMA was used to protect the
      airway. The differences in the risk of regurgitation (RR 0.84, 95% CI 0.27 to
      2.59), vomiting (RR 1.56, 95% CI 0.74 to 3.26), nausea (RR 1.59, 95% CI 0.91 to
      2.78), and the success of insertion on the first attempt (RR 1.08, 95% CI 0.99 to
      1.18) were not statistically significant between the 2 groups. CONCLUSIONS: For
      the patients receiving general anesthesia, the use of the LMA resulted in a
      statistically and clinically significant lower incidence of laryngospasm during
      emergence, postoperative hoarse voice, and coughing than when using an ETT. The
      risk of aspiration could not be determined because only 1 study reported a single
      case of aspiration, which was in the group using the ETT.

PMID- 20674127
TI  - Squamous cell carcinoma recurrence around dental implants.
AB  - PURPOSE: The role of dental implants as part of functional and esthetic oral
      rehabilitation after ablative intraoral tumor surgery has been established. The
      purpose of this article is to highlight the phenomenon of tumor recurrence around
      dental implants. MATERIALS AND METHODS: Twenty-one consecutive cases of patients
      all treated surgically for squamous cell carcinoma of the oral mucosa between
      January 2003 and December 2007 were reviewed, regardless of staging. Dental
      rehabilitation was established by means of oral implants. Fifty-six implants were
      placed either during tumor ablation surgery (16 patients) of afterward (5
      patients). Radiotherapy was given according to the guidelines of the NWHNT
      (Netherlands Working group on Head and Neck Tumors). RESULTS: In the group of
      simultaneous implantation, 3 patients developed local recurrence around one of
      the implants. No recurrence was found in the group implanted in second stage
      surgery. Local recurrence around a dental implant is a severe oncological setback
      that drew our attention. CONCLUSION: Influence on radiation fields and errors in
      surgical techniques are discussed, as well as the possibility of inducing changes
      in sensitized mucosa. Because of the small number of patients, no conclusions can
      be drawn. Further multicentered examinations should be performed.

PMID- 20674128
TI  - Comparison of treatment outcomes associated with early versus late treatment of
      mandible fractures: a retrospective chart review and analysis.
AB  - PURPOSE: We conducted outcomes assessment for all patients who had undergone
      treatment of mandible fractures at Tufts Medical Center across the 2 specialties
      of oral and maxillofacial surgery and otolaryngology. The aim of the present
      study was to determine whether a correlation existed between the development of
      postoperative complications and late treatment of mandible fractures (defined as
      treatment provided >48 hours after the time of injury). PATIENTS AND METHODS: All
      patients with mandible fractures treated at Tufts Medical Center between January
      1, 2003 and January 1, 2008, underwent chart review to document the relevant
      data, including the time of fracture, time of treatment, and complications
      recorded during postoperative follow-up. The only patients included in the review
      were those who had follow-up data with good documentation. RESULTS: Our dataset
      included 92 patients, with a mean age of 28.74 years. The injury scores, compared
      between the early and late treatment and complication and noncomplication groups,
      were equivocal. Of our 92 treated patients, 19 (20.7%) had >=1 postoperative
      complication. Of the 19 patients with any complication, 10 had undergone early
      treatment and 9 had been treated after 48 hours. Of our late treatment group, 25%
      developed >=1 complication. The overall complication rate for the early group was
      18%. CONCLUSIONS: Our study did not reveal a statistically significant difference
      in the development of postoperative complications after mandible fracture repair
      between the early and late treatment groups. Our study seemed to have a result
      similar to that of some of the earlier studies investigating the same variable.

PMID- 20674129
TI  - Biomechanical analysis comparing natural and alloplastic temporomandibular joint
      replacement using a finite element model.
AB  - PURPOSE: Prosthetic materials and bone present quite different mechanical
      properties. Consequently, mandible reconstruction with metallic materials (or a
      mandible condyle implant) modifies the physiologic behavior of the mandible
      (stress, strain patterns, and condyle displacements). The changing of bone strain
      distribution results in an adaptation of the temporomandibular joint, including
      articular contacts. MATERIALS AND METHODS: Using a validated finite element
      model, the natural mandible strains and condyle displacements were evaluated.
      Modifications of strains and displacements were then assessed for 2 different
      temporomandibular joint implants. Because materials and geometry play important
      key roles, mechanical properties of cortical bone were taken into account in
      models used in finite element analysis. RESULTS: The finite element model allowed
      verification of the worst loading configuration of the mandibular condyle.
      Replacing the natural condyle by 1 of the 2 tested implants, the results also
      show the importance of the implant geometry concerning biomechanical mandibular
      behavior. The implant geometry and stiffness influenced mainly strain
      distribution. CONCLUSION: The different forces applied to the mandible by the
      elevator muscles, teeth, and joint loads indicate that the finite element model
      is a relevant tool to optimize implant geometry or, in a subsequent study, to
      choose a more suitable distribution of the screws. Bone screws (number and
      position) have a significant influence on mandibular behavior and on implant
      stress pattern. Stress concentration and implant fracture must be avoided.

PMID- 20674130
TI  - Comparing 3-dimensional virtual methods for reconstruction in craniomaxillofacial
      surgery.
AB  - PURPOSE: In the present project, the virtual reconstruction of digital osteomized
      zygomatic bones was simulated using different methods. MATERIALS AND METHODS: A
      total of 15 skulls were scanned using computed tomography, and a virtual
      osteotomy of the left zygomatic bone was performed. Next, virtual reconstructions
      of the missing part using mirror imaging (with and without best fit registration)
      and thin plate spline interpolation functions were compared with the original
      left zygomatic bone. RESULTS: In general, reconstructions using thin plate spline
      warping showed better results than the mirroring approaches. Nevertheless, when
      dealing with skulls characterized by a low degree of asymmetry, mirror imaging
      and subsequent registration can be considered a valid and easy solution for
      zygomatic bone reconstruction. CONCLUSIONS: The mirroring tool is one of the
      possible alternatives in reconstruction, but it might not always be the optimal
      solution (ie, when the hemifaces are asymmetrical). In the present pilot study,
      we have verified that best fit registration of the mirrored unaffected hemiface
      and thin plate spline warping achieved better results in terms of fitting
      accuracy, overcoming the evident limits of the mirroring approach.

PMID- 20674131
TI  - Inferior vena cava thrombus associated with intravascular cooling catheter.

PMID- 20674132
TI  - Interventions to improve rates of post-mortem examination after stillbirth.
AB  - OBJECTIVE: Despite recognition of the value of post-mortem examination following
      stillbirth, worldwide rates have declined since the early 1990s. There is a
      paucity of published evidence relating to factors that can improve post-mortem
      uptake. The aim of this study was to assess post-mortem rates following
      stillbirth and identify trends in the past 18 years that may have affected
      acceptance of the investigation. STUDY DESIGN: Retrospective cohort study.
      RESULTS: Sharp declines in post-mortems coincided with publicity surrounding
      unlawful organ retention. Although nationally post-mortem rates have continued to
      fall, in our unit there was recovery in post-mortem rates. This increase was
      associated with implementation of policies to promote the uptake of perinatal
      post-mortem, including availability of specialist perinatal pathologists,
      education in the value of post-mortem, and senior staff involvement in
      counselling regarding the procedure. CONCLUSION: The need to improve uptake of
      post-mortem examination following stillbirth is internationally recognized. The
      results of this study suggest that increased local availability of specialist
      perinatal pathologists, who can support education in the value of post-mortem,
      along with senior staff obtaining consent, may help achieve this goal.

PMID- 20674133
TI  - Notes on a stick: use and acceptability of woman-held maternity notes.
AB  - OBJECTIVE: To provide expectant mothers with a USB stick containing their
      maternity notes, including ultrasound images, and to assess its use and
      acceptability versus conventional care with exclusively hospital-held notes.
      STUDY DESIGN: USB group: 200 women attending Zurich University Hospital
      Obstetrics Department for antenatal-to-postnatal care in 2006-2007. CONTROLS: 200
      women attending the Obstetrics Department for delivery only, after receiving
      conventional antenatal care elsewhere. Women were interviewed using an
      essentially identical postpartum questionnaire for each group, with minor wording
      differences. MAIN OUTCOME MEASURES: Overall satisfaction with pregnancy and
      delivery, feeling of safety, interest in the pregnancy, partner involvement,
      usefulness of USB stick in emergencies, impact on smoking behaviour, data
      confidentiality concerns, pregnancy and infant outcome. Stepwise multiple
      regression was used to identify determinants of overall impressions of pregnancy
      and delivery. RESULTS: Of the USB group, 98.5% wished to repeat the USB
      experience in a subsequent pregnancy; of the controls, 86.5% would have
      appreciated the experience, and 18.0% could think of situations in their
      pregnancy (vacation, emergencies) where the stick would have helped; 7.5% of the
      USB group shared their stick data with a doctor outside the Department, and 80.5%
      felt safer having the stick available. Along with preterm delivery and mode of
      delivery, the USB stick was a significant determinant of the overall positive
      impression of pregnancy. Primary caesarean section was (inexplicably) more
      frequent in the USB group. CONCLUSION: The questionnaire confirmed that issuing
      women with their maternity notes on a USB stick is a major advance in patient
      empowerment, satisfaction and safety.

PMID- 20674134
TI  - Perinatal morbidity and mortality in twin pregnancies with dichorionic placentas
      following assisted reproductive techniques or ovarian induction alone: a
      comparative study.
AB  - OBJECTIVE: To compare maternal and perinatal outcome in non-spontaneously and
      spontaneously conceived dichorionic twin pregnancies. STUDY DESIGN: We report a
      retrospective study of all 350 twin pregnancies delivered >=22 weeks of gestation
      between January 1, 2001 and December 31, 2005 in a tertiary maternity unit. We
      compared maternal outcome, perinatal morbidity and neonatal mortality between
      spontaneous and non-spontaneous dichorionic twin pregnancies, with a subgroup
      analysis separating pregnancies following assisted reproduction technology (ART
      group) from those following ovarian induction alone (OI group). Generalized
      linear model and multivariate analysis were performed. RESULTS: The proportion of
      primiparous women and the mean maternal age were higher in the non-spontaneously
      conceived dichorionic twin pregnancy group as expected (70.2% vs. 38.2%, p<0.001
      and 32.1 +/- 3.8 vs. 30.7 +/- 4.6 years, p<0.01). Multivariate analysis, adjusted
      for maternal age and parity, revealed that non-spontaneously conceived
      dichorionic twin pregnancies were associated with a higher risk of very preterm
      birth (OR 2.20, 95% confidence interval 1.02-4.77, p<0.05), low birth weight
      (1.77, 1.21-2.61, p<0.01), very low birth weight (1.99, 1.13-3.49, p<0.05), NICU
      admission (1.66, 1.14-2.43, p<0.01), and fetal or neonatal death (3.21, 1.30
      7.95, p<0.05). Multivariate analysis confirmed that the mean gestational age
      (p<0.01) and mean birth weight of the first (p<0.05) and second twins (p<0.01)
      were lower in the non-spontaneously conceived dichorionic twin pregnancy group.
      These associations were confirmed in the OI group analysis (n=39) but not in the
      ART group (n=65). Ovarian induction was associated with an increase in the risk
      of preterm and very preterm births (2.25, 1.06-4.75, p<0.05 and 3.47, 1.42-8.49,
      p<0.01, respectively), low and very low birth weights (2.87, 1.63-5.05, p<0.001
      and 2.59, 1.33-5.07, p<0.01, respectively), NICU admission (2.92, 1.67-5.11,
      p<0.001) and fetal or neonatal death (4.20, 1.40-12.56, p<0.05). The mean
      gestational age (p<0.001) and mean birth weight of the first (p<0.01) and second
      twins (p<0.001) were also lower in the OI group. CONCLUSIONS: Twin pregnancies
      with dichorionic placentation following non-spontaneously conceived pregnancy are
      associated with a higher risk of adverse perinatal outcome compared with
      dichorionic spontaneously conceived twin pregnancies especially in case of
      ovarian induction alone.

PMID- 20674135
TI  - National survey on management of weight reduction in PCOS women in the United
      Kingdom.
AB  - OBJECTIVE: To identify the most commonly used methods for weight reduction in
      women with polycystic ovarian syndrome (PCOS) utilized by obstetricians and
      gynaecologists in the United Kingdom (UK). STUDY DESIGN: Permission was sought
      from the Royal College of Obstetricians and Gynaecologists (RCOG) to conduct an
      electronic survey of all consultants practising in the UK. The questionnaire was
      anonymous and an electronic link was sent via email to the 1140 consultants whose
      details were provided by the RCOG. A 27-item questionnaire was developed. The
      variables evaluated were first-line methods of weight reduction used, proportion
      of women with PCOS seen that were obese, whether the patients had tried other
      weight reduction methods before seeking help, the optimal dietary advice and
      optimal composition, the optimal duration and frequency of exercise suggested,
      BMI used for suggesting weight loss, percentage of women in whom weight loss
      worked, length of time allowed prior to suggesting another method, methods
      considered most effective by patients, use of metformin for weight loss, criteria
      used for prescribing metformin, first-line anti-obesity drugs preferred if any,
      second- and third-line methods used, referral to other specialists and criteria
      for referral for bariatric surgery. Responses were categorical and are reported
      as proportions. RESULTS: One hundred and seven (9.4%) consultants responded to
      the questionnaire. One hundred and four (97%) provided advice on diet and 101
      (94%) advice on exercise as their first-line strategy for weight management.
      Fifty-one (47.7%) stated that they provided specific information on an optimal
      dietary intake, 53 (49.9%) on the optimal dietary composition and 61 (57%) on the
      optimal duration and frequency of exercise per week. The commonest second-line
      methods used were anti-obesity drugs and metformin and the most popular third
      line management options were anti-obesity drugs and bariatric surgery.
      CONCLUSIONS: The results suggest that the information provided to women with PCOS
      on weight management is variable, and highlight the need for specific guidelines
      and further research on weight management in women with this condition.

PMID- 20674136
TI  - Maternal gastric carcinoma metastatic to the placenta.

PMID- 20674137
TI  - Symptomatic pelvic hematoma following transvaginal reconstructive pelvic surgery:
      incidence, clinical presentation, risk factors, and outcome.
AB  - OBJECTIVE: To assess the incidence, clinical presentation, risk factors and
      outcome of symptomatic pelvic hematomas following transvaginal pelvic
      reconstructive surgery. MATERIALS AND METHODS: We reviewed the medical records of
      all women undergoing transvaginal reconstructive pelvic surgery in our
      institution between January 2006 and July 2009. RESULTS: 462 patients underwent
      pelvic reconstructive surgery, of whom 28 (6%) presented with symptomatic pelvic
      hematomas. All cases occurred after transvaginal hysterectomy, 25 (90%) presented
      with fever, 20 (71%) with pelvic pain and 5 (20%) with urinary retention. All
      hematomas were diagnosed by ultrasound. They were located at the vaginal cuff in
      18 (64%), anterior vaginal wall in six (21%) and posterior vaginal wall in four
      patients (14%), and had a mean volume of 590 +/- 140 cm(3). Laboratory data
      included leukocytosis (71%), thrombocytosis (57%) and elevated liver enzymes
      (18%). Nine patients (33%) required ultrasound-guided drainage of the hematoma,
      which resulted in marked clinical improvement. Surgical outcome was not affected
      by the presence of pelvic hematoma. CONCLUSIONS: A postoperative symptomatic
      pelvic hematoma is not rare and is closely related to transvaginal hysterectomy.
      Its clinical presentation includes fever, pelvic pain, leukocytosis,
      thrombocytosis and occasionally liver dysfunction. Surgical outcome is generally
      unaffected.

PMID- 20674138
TI  - Amino-terminal pro-brain natriuretic peptide (NT-proBNP) is a biomarker of
      cardiac filling pressures in pre-eclampsia.
AB  - OBJECTIVE: To evaluate if amino-terminal pro-brain natriuretic peptide (NT
      proBNP) plasma levels reflect intracardiac filling pressures in pre-eclamptic
      patients. STUDY DESIGN: In a cross-sectional study we investigated 22 untreated
      critically ill pre-eclamptic women between 22 and 34 weeks gestation. All
      patients underwent intra-arterial blood pressure and central hemodynamic
      measurements and NT-proBNP was determined in stored plasma. Baseline
      characteristics, plasma NT-proBNP concentrations and relevant laboratory
      variables were investigated for correlations with hemodynamic values using
      Spearman's rank correlation test. RESULTS: No significant correlations were
      demonstrated between NT-proBNP concentrations and variables associated with the
      severity of the pre-eclampsia. We found significant positive correlations between
      NT-proBNP and diastolic pulmonary pressure (r = 0.59; p = 0.005) and pulmonary
      capillary wedge pressure (PCWP) (r = 0.51; p = 0.015). Multiple linear regression
      analysis showed that the association between NT-proBNP and PCWP was not affected
      by creatinine level. CONCLUSION: NT-proBNP is a biomarker of left ventricular
      cardiac filling pressures in untreated pre-eclamptic patients.

PMID- 20674139
TI  - Evaluation of pelvic floor muscle cross-sectional area using a 3D computer model
      based on MRI in women with and without prolapse.

PMID- 20674140
TI  - Effect of sphingosine-1-phosphate supplementation on follicular integrity of
      vitrified-warmed mouse ovarian grafts.
AB  - OBJECTIVE: To investigates the effect of sphingosine-1-phosphate (S1P)
      supplementation on follicular integrity and apoptosis in vitrified-warmed mouse
      ovarian grafts. STUDY DESIGN: Ovaries from 4-week-aged ICR mice were vitrified
      using a vitrification solution with or without 2 MUM S1P. After warming,
      follicular normality was assessed by histological analysis and TUNEL assay. A
      part of ovaries vitrified with or without 2 MUM S1P was transplanted, and 2 weeks
      later, gross and microscopic follicular morphology was assessed. RESULTS: During
      vitrification and warming, inclusion of 2 MUM S1P into the vitrification solution
      significantly raised the rate of morphologically intact follicles compared to
      controls (36.6% vs. 30.8%, p=0.047). This protective effect was profound
      especially in primordial follicles (45.5% vs. 34.6%, p=0.034). After
      transplantation of vitrified-warmed ovaries, the morphological integrity of
      primordial follicles was superior in the S1P-treated group (55.0% vs. 39.4%,
      p=0.035). The rates of non-apoptotic follicles (TUNEL-negative) were similar in
      the two groups in either non-transplanted or transplanted ovaries. CONCLUSION:
      Inclusion of S1P in the vitrification solution during transplantation of
      vitrified-warmed ovary had a beneficial effect on preservation of the primordial
      follicular pool.

PMID- 20674141
TI  - Transvaginal repair of genital prolapse with polypropylene mesh using a tension
      free technique.
AB  - OBJECTIVES: To assess the perioperative complications and short-term outcomes of
      prolapse repair using transvaginal polypropylene mesh. STUDY DESIGN:
      Retrospective study. In the period from April 2007 to September 2009, 67 women
      underwent vaginal repair with implantation of a soft mesh manufactured by
      Gynecare. RESULTS: All the patients had a stage 3 or stage 4 prolapse. Total mesh
      was used in eight patients (11.9%), isolated anterior mesh in 36 patients (53.7%)
      and isolated posterior mesh in 23 patients (34.4%). We reported one
      intraoperative bladder injury and no other serious complications. At 3 months,
      all the 67 patients were available for follow-up. Vaginal erosion occurred in
      eight patients (11.9%), shrinkage of mesh in six patients (8.7%), granuloma
      without exposure in four patients (5.9%), de novo urinary incontinence in three
      patients (4.5%) and flatus incontinence in one patient (1.5%). Failure rate was
      7.5% (recurrent prolapse stage 3 or 4, even asymptomatic). CONCLUSION: Our study
      suggests that transvaginal polypropylene mesh applied with a tension-free
      technique is a safe and effective method with low intraoperative complications
      but with considerable potential postoperative morbidity.

PMID- 20674142
TI  - Necrotic adnexal tumor after detorsion in pregnancy: excise or leave?

PMID- 20674143
TI  - Molecular evidence of stereo-specific lactoferrin dimers in solution.
AB  - Gathering experimental evidence suggests that bovine as well as human lactoferrin
      self-associate in aqueous solution. Still, a molecular level explanation is
      unavailable. Using force field based molecular modeling of the protein-protein
      interaction free energy we demonstrate (1) that lactoferrin forms highly stereo
      specific dimers at neutral pH and (2) that the self-association is driven by a
      high charge complementarity across the contact surface of the proteins. Our
      theoretical predictions of dimer formation are verified by electrophoretic
      mobility and N-terminal sequence analysis on bovine lactoferrin.

PMID- 20674144
TI  - Detection capacity, information gaps and the design of surveillance programs for
      invasive forest pests.
AB  - Integrated pest risk maps and their underlying assessments provide broad guidance
      for establishing surveillance programs for invasive species, but they rarely
      account for knowledge gaps regarding the pest of interest or how these can be
      reduced. In this study we demonstrate how the somewhat competing notions of
      robustness to uncertainty and potential knowledge gains could be used in
      prioritizing large-scale surveillance activities. We illustrate this approach
      with the example of an invasive pest recently detected in North America, Sirex
      noctilio Fabricius. First, we formulate existing knowledge about the pest into a
      stochastic model and use the model to estimate the expected utility of
      surveillance efforts across the landscape. The expected utility accounts for the
      distribution, abundance and susceptibility of the host resource as well as the
      value of timely S. noctilio detections. Next, we make use of the info-gap
      decision theory framework to explore two alternative pest surveillance
      strategies. The first strategy aims for timely, certain detections and attempts
      to maximize the robustness to uncertainty about S. noctilio behavior; the second
      strategy aims to maximize the potential knowledge gain about the pest via
      unanticipated (i.e., opportune) detections. The results include a set of spatial
      outputs for each strategy that can be used independently to prioritize
      surveillance efforts. However, we demonstrate an alternative approach in which
      these outputs are combined via the Pareto ranking technique into a single
      priority map that outlines the survey regions with the best trade-offs between
      both surveillance strategies.

PMID- 20674145
TI  - Subsoil TPH contamination in two oil pipeline pumping stations and one pipeline
      right-of-way in north Mexico.
AB  - This investigation deals with the characterization carried out in zones around
      two pipeline pumping stations and one pipeline right-of-way in the north of
      Mexico. In particular those areas where contamination was evaluated: (a) south
      area of the separation ditch in the Avalos station, (b) the area between the
      separation ditch at the Avalos station, (c) km 194+420 of the Moctuzma station,
      and (d) km 286+900 in the Candelaria station. Results of this investigation
      showed that only four samples showed TPH values higher than the Mexican limit for
      2004: AVA 1B, with 21,191 mg kg(-1); AVA 1C, with 9348 mg kg(-1); AVA 2B, with
      13,970 mg kg(-1); and MOC 2A, with 4108 mg kg(-1).None of the sampled points
      showed the presence of PAHs at values higher than those found in the Mexican or
      American legislations. PAH were detected in the range of 0.0004 and 13.05 mg kg(
      1).It is suggested to implement surfactant soil washing as a remediation
      technique for the approximately 600 m(3) that need to be treated.

PMID- 20674146
TI  - A multi-criteria approach for the dumping of dredged material in the Thermaikos
      Gulf, Northern Greece.
AB  - A multi-criteria approach was applied for the disposal into the sea of ~1,100,000
      m(3) of sediment, dredged from a coastal area in the northeastern part of the
      Thermaikos Gulf. This sediment (classified as muddy) is distributed vertically
      into two distinct Layers (A and B) with the thickness of the surficial
      sedimentary unit ranging from 7 to 54 cm. Its geochemistry reveals increased Cr
      and Ni concentrations, which may be attributed to natural enrichment through the
      erosion of the adjacent igneous and metamorphic rocks. In addition, a low to
      moderate contamination from urban-originated heavy metals, like Cu, Pb and Zn as
      well as from aliphatic and polycyclic hydrocarbons was identified for the upper
      Layer A. However, the limited proportion (5.5%) of the polluted Layer A in the
      total volume of the dredged material could not affect the good quality (assessed
      by the Sediment Quality Guidelines) of the bulk sediment. The identification of
      the optimum marine dumping site was based on (a) the physicochemical similarity
      (detected by the application of a cluster analysis) of the dredged material with
      the surficial deposits of potential dumping sites in the Outer Thermaikos Gulf,
      and (b) the consideration, based on previous studies, of various criteria related
      to the disposal area such as deep-water circulation, influence on living
      resources, impact on economical (aquaculture, fishing, navigation), recreational
      (fishing) and military activities.

PMID- 20674147
TI  - Surface water quality and its control in a river with intensive human impacts--a
      case study of the Xiangjiang River, China.
AB  - Surface water quality and its natural and anthropogenic controls in the
      Xiangjiang River were investigated using multivariate statistical approaches and
      a comprehensive observation dataset collected from 2004 to 2008. Cluster analysis
      (CA) grouped the 15 different sampling stations into five clusters with similar
      hydrochemistry characteristics and pollution levels. Four principal components
      (PCs), nutrients, heavy metals, natural components, and organic components, were
      extracted from the entire dataset. Comparison of the different regional
      characteristics of these four PCs revealed a decreasing trend for heavy metals
      and an increasing trend for organic factor on an annual scale, and the seasonal
      trend was only observed for natural factor. We also conducted analysis of
      variance (ANOVA) in combination with principal component analysis (PCA) to
      quantify the relative contribution of spatial and temporal variations to each of
      the four PCs. The results revealed that 62% of the contributions from the spatial
      sites were responsible for variations in heavy metals, while 83% of the
      contributions from the sampling time were responsible for natural variations
      observed. However, no significant spatial or temporal contributions were found to
      be responsible for the nutrient and organic variations. Finally, some suggestions
      regarding water management were put forward based on the current status and
      future trends of surface water quality in the Xiangjiang River.

PMID- 20674148
TI  - Treatment of E. coli HB101 and the tetM gene by Fenton's reagent and ozone in cow
      manure.
AB  - The destruction of antibiotic-resistant microorganisms at the source of
      contamination is necessary due to their adverse effects and to their increasingly
      widespread occurrence in the environment. To address this problem, Fenton and
      ozone oxidation processes were applied to synthetically contaminated cow manure
      to remove the tetM gene and its host, Escherichia coli HB101. The efficiency of
      the processes was evaluated by enumeration of E. coli HB101 and by PCR
      amplification of the tetM gene. The results of this study show that 56.60%
      bacterial inactivation (corresponding to a 0.36 log reduction) was achieved by a
      Fenton reagent dose of 50 mM H(2)O(2) and 5 mM Fe(2+) without acidifying the
      manure. Despite the high organic content of cow manure, 98.50% bacterial
      inactivation (corresponding to a 1.83 log reduction) was obtained by the
      ozonation process with an applied dose of 3.125 mg ozone/g manure slurry. The PCR
      study revealed that the band intensity of the tetM gene gradually decreased by
      increasing the Fenton reagent and the applied ozone dose. However, significantly
      high doses of oxidants would be required to completely eliminate bacterial
      pollution in manure.

PMID- 20674149
TI  - Efficacy and tolerability of botulinum toxin type A in patients with neurogenic
      detrusor overactivity and without concomitant anticholinergic therapy: comparison
      of two doses.
AB  - BACKGROUND: Botulinum toxin type A (BoNTA) has been reported to be effective for
      treatment of patients with neurogenic detrusor overactivity (NDO) refractory to
      anticholinergic agents. However, in most of the studies, the efficacy was
      associated with concomitant use of anticholinergics. OBJECTIVE: To evaluate the
      efficacy and tolerability of BoNTA and compare two different doses in patients
      with NDO without concomitant anticholinergics. DESIGN, SETTING, AND PARTICIPANTS:
      Between 2004 and 2006, adults with NDO refractory to anticholinergics or
      discontinued anticholinergics due to adverse events or contraindications from
      four different French clinical centres were included in a prospective,
      randomised, double-blind, comparative trial. Inclusion criteria were urinary
      incontinence (UI) resulting from NDO that could not be managed with
      anticholinergics. Patients with bladder cancer, lithiasis, or urinary infection
      were excluded. INTERVENTION: Patients were randomised to receive an intradetrusor
      injection of 500 U or 750 U of BoNTA. MEASUREMENTS: The initial evaluation (ie,
      clinical and urodynamic variables and quality of life [QoL]) was repeated at days
      30, 90, 180, and 360. Primary outcome was complete continence rate at day 30.
      Secondary outcomes were cumulative incontinence rate, reappearance of leakages,
      pad usage, urodynamics, and QoL. RESULTS AND LIMITATIONS: Seventy-seven patients
      received 500 U (n=39) or 750 U (n=38) of BoNTA and were included in the full
      analysis set for efficacy analysis. Complete continence at day 30 was observed in
      22 patients (56.4%) and 28 patients (73.7%) receiving 500 U or 750 U of BoNTA,
      respectively (p=0.056; one-sided chi(2) test to compare to alpha=0.025). The
      median delay in the reappearance of leakages was 168 d. Monotherapy of BoNTA
      significantly improved UI in patients with NDO. Although there was a trend
      towards a greater improvement with 750 U of BoNTA, no statistically significant
      differences in terms of clinical and urodynamic variables and QoL were found
      between the treatment groups. Tolerability was excellent and equivalent for both
      doses. CONCLUSIONS: Monotherapy of BoNTA at Dysport (Ipsen, Brisbane, CA, USA)
      doses of 500 U or 750 U seems to be effective and well tolerated in patients with
      NDO.

PMID- 20674151
TI  - Molecular mechanisms of vacuum therapy in penile rehabilitation: a novel animal
      study.
AB  - BACKGROUND: Penile rehabilitation (PR) is widely applied after radical
      prostatectomy. Vacuum erectile device (VED) therapy is the one of three PR
      methods used in the clinical setting that improve erectile function (EF) and is
      the only PR method which may preserve penile length. However, its unknown
      mechanism hampered doctors' recommendations and patients' compliance. OBJECTIVES:
      To assess the effects of VED therapy on erectile dysfunction (ED) in a rat model
      of bilateral cavernous nerve crush (BCNC) and to investigate the molecular
      mechanism of VED in postprostatectomy ED. DESIGN, SETTING, AND PARTICIPANTS: This
      was an experimental study using Sprague-Dawley rats in three groups: sham, BCNC,
      and BCNC plus VED. INTERVENTION: Intervention included BCNC, electrical
      stimulation of the cavernous nerve (CNS), and VED therapy. MEASUREMENTS: At the
      end of a 4-wk period, CNS was used to assess EF by maximum intracavernosal
      pressure (ICP)/mean arterial pressure (MAP) ratio and duration (area under the
      curve [AUC]). For the structural analyses, whole rat penis was harvested.
      Terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling assay was
      used for the assessment of apoptotic indices (AI). Immunohistochemistry was
      performed for endothelial nitric oxide synthase (eNOS), alpha-smooth muscle actin
      (ASMA), transforming growth factor beta 1 (TGF-beta1), and hypoxia inducible
      factor-1alpha (HIF-1alpha). Staining for Masson's trichrome was utilized to
      calculate the smooth muscle/collagen ratios. RESULTS AND LIMITATIONS: EF was
      improved with VED therapy measured by ICP/MAP ratios and AUC. VED therapy reduced
      HIF-1alpha expression and AI significantly compared with control. Animals exposed
      to VED therapy had decreased TGF-beta1 expression, increased smooth
      muscle/collagen ratios, and preserved ASMA and eNOS expression. CONCLUSIONS: To
      our knowledge, this is the first scientific study to suggest that VED therapy in
      the BCNC rat model preserves EF through antihypoxic, antiapoptotic, and
      antifibrotic mechanisms.

PMID- 20674150
TI  - Validation of the 2009 TNM version in a large multi-institutional cohort of
      patients treated for renal cell carcinoma: are further improvements needed?
AB  - BACKGROUND: A new edition of the TNM was recently released that includes
      modifications for the staging system of kidney cancers. Specifically, T2 cancers
      were subclassified into T2a and T2b (< or =10 cm vs >10 cm), tumors with renal
      vein involvement or perinephric fat involvement were classified as T3a cancers,
      and those with adrenal involvement were classified as T4 cancers. OBJECTIVE: Our
      aim was to validate the recently released edition of the TNM staging system for
      primary tumor classification in kidney cancer. DESIGN, SETTING, AND PARTICIPANTS:
      Our multicenter retrospective study consisted of 5339 patients treated in 16
      academic Italian centers. INTERVENTION: Patients underwent either radical or
      partial nephrectomy. MEASUREMENTS: Univariable and multivariable Cox regression
      models addressed cancer-specific survival (CSS) after surgery. RESULTS AND
      LIMITATIONS: In the study, 1897 patients (35.5%) were classified as pT1a, 1453
      (27%) as pT1b, 437 (8%) as pT2a, 153 (3%) as pT2b, 1059 (20%) as pT3a, 117 (2%)
      as pT3b, 26 (0.5%) as pT3c, and 197 (4%) as pT4. At a median follow-up of 42 mo,
      786 (15%) had died of disease. In univariable analysis, patients with pT2b and
      pT3a tumors had similar CSS, as did patients with pT3c and pT4 tumors. Moreover,
      both pT3a and pT3b stages included patients with heterogeneous outcomes. In
      multivariable analysis, the novel classification of the primary tumor was a
      powerful independent predictor of CSS (p for trend <0.0001). However, the
      substratification of pT1 tumors did not retain an independent predictive role.
      The major limitations of the study are retrospective design, lack of central
      pathologic review, and the small number of patients included in some substages.
      CONCLUSIONS: The recently released seventh edition of the primary tumor staging
      system for kidney tumors is a powerful predictor of CSS. However, some of the
      substages identified by the classification have overlapping prognoses, and other
      substages include patients with heterogeneous outcomes. The few modifications
      included in this edition may have not resolved the most critical issues in the
      previous version.

PMID- 20674152
TI  - The use of intraoperative suprasellar pneumocisternogram for resection of large
      pituitary tumors.
AB  - Adequate removal of large pituitary tumors with significant suprasellar extension
      remains a challenge through the trans-sphenoidal corridor because of this route's
      limited working window. The application of intracisternal air and intraoperative
      fluoroscopy is explored as a form of intraoperative imaging to maximize tumor
      resection and to confirm adequate suprasellar tumor decompression. The authors
      confirmed adequate decompression of suprasellar space using this technique of
      fluoroscopy with the present intrathecal air for 10 of 12 patients with giant,
      non-functioning pituitary tumors. Intraoperative cerebrospinal fluid fistulae
      prevented the use of intrathecal air in the remaining two patients.

PMID- 20674153
TI  - Icariin, a natural flavonol glycoside, induces apoptosis in human hepatoma SMMC
      7721 cells via a ROS/JNK-dependent mitochondrial pathway.
AB  - In this study, the anticancer effect of icariin, a natural flavonol glycoside,
      against human hepatoma SMMC-7721 cells and the underlying mechanisms were
      investigated. Icariin triggered the mitochondrial/caspase apoptotic pathway
      indicated by enhanced Bax-to-Bcl-2 ratio, loss of mitochondrial membrane
      potential, cytochrome c release, and caspase cascade. Moreover, icariin induced a
      sustained activation of the phosphorylation of c-Jun N-terminal kinase (JNK) but
      not p38 and ERK1/2, and SP600125 (an inhibitor of JNK) almost reversed icariin
      induced apoptosis in SMMC-7721 cells. In addition, icariin provoked the
      generation of reactive oxygen species (ROS) in SMMC-7721 cells, while the
      antioxidant N-acetyl cysteine almost completely blocked icariin-induced JNK
      activation and apoptosis. Taken together, these findings suggest that icariin
      induces apoptosis through a ROS/JNK-dependent mitochondrial pathway.

PMID- 20674155
TI  - The role of Ca pathway in Cd uptake and translocation by the hyperaccumulator
      Sedum alfredii.
AB  - Effect of Ca on plant growth, Cd uptake and translocation in the hyperaccumulator
      Sedum alfredii was investigated, as to reveal the possible pathway of Cd entry
      into the plants system. High Ca increased plant growth under Cd stress after 7 d,
      and significantly affected the total Cd influx and translocation rate. Short-term
      kinetics of (109)Cd influx performed using radiotracers confirmed a significant
      inhibition of (109)Cd influx into the roots induced by high Ca. Under exposure of
      5.0 mM Ca, K(m) of (109)Cd influx into roots was 2-fold higher in the
      hyperaccumulator, although the V(max) value remained at similar level, when
      compared with the treatments of 0.5 mM Ca. Calcium concentrations in xylem sap of
      the hyperaccumulator decreased with the increasing Cd levels and significant
      negative correlationship between the two elements was observed. However,
      increased xylem loading of Cd was observed in the hyperaccumulator in response to
      the increasing exogenous Ca level from 0.5 to 4.0 mM, but reverse effect was
      observed when higher Ca levels (8-32 mM) were presented in the solutions. These
      results suggest that Cd uptake and translocation in the hyperaccumulator S.
      alfredii plants is positively associated with Ca pathway.

PMID- 20674154
TI  - NO-releasing NSAIDs suppress NF-kappaB signaling in vitro and in vivo through S
      nitrosylation.
AB  - NO-NSAIDs are promising anticancer drugs, comprising an NSAID, an NO-releasing
      moiety, and a spacer linking them. Although the effect of NO-NSAIDs on a wide
      variety of signaling and other cellular mechanisms has been deciphered, a key
      question remains unanswered, that being the role of NO to the overall biological
      effect of these agents. It has been shown that NO can directly modify sulfhydryl
      residues of proteins through S-nitrosylation and induce apoptosis. We studied 3
      NO-NSAIDs having a different NSAID, spacer, and NO-releasing moiety. In vitro:
      aspirin, NO-ASA, naproxen, and NO-naproxen inhibited HT-29 human colon cancer
      cell growth, the IC(50)s being >5000, 192+/-6, 2800+/-210 and 95+/-5MUM at 24h,
      respectively. NO-Aspirin and NO-naproxen reduced NF-kappaB protein levels, and
      activated caspase-3 enzyme in a dose- and time-dependent manner. Based on the
      biotin switch assay, NO-ASA and NO-naproxen S-nitrosylated NF-kappaB p65 in a
      time-dependent manner. Pretreatment of the cells with carboxy-PTIO, abrogated the
      S-nitrosylation of NF-kappaB p65. In vivo: rats treated with NO-ASA, NONO-ASA,
      and NO-naproxen showed S-nitrosylation of NF-kappaB p65 in the stomach tissue,
      increases in plasma TNF-alpha, and reductions in mucosal PGE(2) levels. These
      data provide a mechanistic role for NO and a rational for the chemopreventive
      effects of NO-NSAIDs.

PMID- 20674156
TI  - Adsorption and desorption of Cu(II), Cd(II) and Pb(II) ions using chitosan
      crosslinked with epichlorohydrin-triphosphate as the adsorbent.
AB  - In this study, chitosan (CTS) was crosslinked with both epichlorohydrin (ECH) and
      triphosphate (TPP), by covalent and ionic crosslinking, respectively. The
      resulting new CTS-ECH-TPP adsorbent was characterized by CHN analysis, EDS, FTIR
      spectroscopy, TGA and DSC, and the adsorption and desorption of Cu(II), Cd(II)
      and Pb(II) ions in aqueous solution were investigated. Potentiometric studies
      were also performed and revealed three titratable protons for each pK(a) value of
      5.14, 6.76 and 9.08. The results obtained showed that the optimum pH values for
      adsorption were 6.0 for Cu(II), 7.0 for Cd(II) and 5.0 for Pb(II). The kinetics
      study demonstrated that the adsorption process proceeded according to the pseudo
      second-order model. Three isotherm models (Langmuir, Freundlich and Dubinin
      Radushkevich) were employed in the analysis of the adsorption equilibrium data.
      The Langmuir model resulted in the best fit and the new adsorbent had maximum
      adsorption capacities for Cu(II), Cd(II) and Pb(II) ions of 130.72, 83.75 and
      166.94 mg g(-1), respectively. Desorption studies revealed that HNO(3) and HCl
      were the best eluents for desorption of Cu(II), Cd(II) and Pb(II) ions from the
      crosslinked chitosan.

PMID- 20674157
TI  - A seasonal study of polycyclic aromatic hydrocarbons in PM(2.5) and PM(2.5-10) in
      five typical cities of Liaoning Province, China.
AB  - Fourteen polycyclic aromatic hydrocarbons (PAHs) in PM(2.5) and PM(2.5-10)
      samples collected in five cities (Shenyang, Anshan, Jinzhou, Fushun and Dalian),
      Liaoning Province, China in 2004 and 2005 were analyzed by using a HPLC equipped
      with fluorescence and UV detectors. Results showed total PAHs concentrations in
      PM(2.5) and PM(2.5-10) were in the range of 75.32-1900.89 ng m(-3) and 16.74
      303.24 ng m(-3), respectively. 90% of the total PAHs were in PM(2.5). PAHs in
      PM(2.5) had a winter to summer ratio varying from 6.5 to 125.8 while PAHs in
      PM(2.5-10) had a ratio ranging from 1.7 to 37.6. Total PAHs concentrations were
      most abundant at residential/commercial sites and were fewest at an industrial
      site for both PM(2.5) and PM(2.5-10). Urban background sites showed unexpected
      higher PAHs concentrations. Total BaP equivalent concentration (BaPeq) for
      PM(2.5) ranged from 7.80 to 88.42 ng m(-3) in different function zones.
      Similarities of PAHs profiles between sampling sites and between fine and coarse
      fractions were compared by coefficient of divergence which indicated that
      remarkable differences in PAHs compositions existed. Principal component analysis
      (PCA) associated with diagnostic ratios revealed coal combustion and vehicle
      emission were the major sources for PM(2.5) and PM(2.5-10) associated PAHs.

PMID- 20674158
TI  - Application of sequential extractions and X-ray absorption spectroscopy to
      determine the speciation of chromium in Northern New Jersey marsh soils developed
      in chromite ore processing residue (COPR).
AB  - The Cr speciation in marsh soils developed in weathering chromite ore processing
      residue (COPR) was characterized using sequential extractions and synchrotron
      microbeam and bulk X-ray absorption spectroscopic (XAS) analyses. The sequential
      extractions suggested substantial Cr associated with reducible and oxidizable
      soil components, and significant non-extractable residual Cr. Notable differences
      in Cr speciation estimates from three extraction schemes underscore the
      operationally defined nature of Cr speciation provided by these methods. Micro X
      ray fluorescence maps and MU-XAS data indicated the presence of MUm-sized
      chromite particles scattered throughout the weathered COPR matrix. These
      particles derive from the original COPR material, and have relatively high
      resistance towards weathering, and therefore persist even after prolonged
      leaching. Bulk XAS data further indicated Cr(III) incorporated in Fe(OH)(3), and
      Cr(III) associated with organic matter. The low Cr contents of the weathered
      material (200-850 ppm) compared to unweathered COPR (20,000-60,000 ppm) point to
      substantial Cr leaching during COPR weathering, with partial repartitioning of
      released Cr into secondary Fe(OH)(3) phases and organics. The effects of anoxia
      on Cr speciation, and the potential of active COPR weathering releasing Cr(VI)
      deeper in the profile require further study.

PMID- 20674159
TI  - The role of iodine monochloride for the oxidation of elemental mercury.
AB  - The removal of Hg(0) by the homogenous gas-phase reaction and particle-induced
      reaction was investigated under various conditions. Iodine monochloride was found
      to be efficient for Hg(0) oxidation, with the apparent 2nd-order rate constant of
      about 10.5(+/-0.3)*10(-17) cm(3) molecules(-1) s(-1) and 5.7(+/-0.3)*10(-17)
      cm(3) molecules(-1) s(-1) at 273 K and 373 K, respectively. The pilot-scale tests
      showed that the removal of Hg(0) by ICl increased significantly in presence of
      flyash. It was predicted that over 90% of Hg(0) removal efficiency can be
      obtained with 0.2 ppmv ICl and 20 g/m(3) flyash in flue gas. Though the reaction
      between Hg(0) and ICl was by far faster than that of Hg(0)/Cl(2), the major
      product was found to be HgCl(2) rather than HgI(2), which implicated that iodine
      might partly act as the accelerant in Hg(0) oxidation by facilitating the
      formation of certain intermediates. The results indicated that using ICl to
      oxidize elemental mercury in coal-fired flue gas can save the consumption of
      iodine, and it appeared to be a promising oxidant to enhance the removal of
      Hg(0).

PMID- 20674160
TI  - Chemical characterization of dust particles recovered from bag filters of
      electric arc furnaces for steelmaking: some factors influencing the formation of
      hexachlorobenzene.
AB  - To make clear some factors controlling the formation of hexachlorobenzene (HCB)
      in the process of electric arc furnace (EAF) steelmaking, six dust samples
      recovered from different bag filters in commercial EAF steelmaking plants have
      been characterized with XRD, SEM-EPMA, XPS and temperature-programmed desorption
      (TPD) techniques. These dust samples contain 1.9-8.0 mass% of chlorine element,
      and the XPS and TPD measurements exhibit that the Cl is enriched at the dust
      surface and composed of the inorganic and organic functionalities, part of the Cl
      being evolved as HCl in the temperature region of flue gas treatment. All of the
      samples also include 2.1-6.4 mass% of carbon element, and some of the C can
      release CO(2) in the TPD up to 300 degrees C to form active carbon sites. The
      number is related closely to HCB concentration of each dust. Further, it is
      suggested that the Zn present in the samples consists of ZnFe(2)O(4), ZnO and
      surface ZnCO(3), and the dust with a larger content of the ZnCO(3) has a higher
      concentration of HCB. It is possible that HCB formation occurs via gas-solid
      solid interactions among gaseous Cl-containing compounds in flue gas, active
      carbon sites and surface Zn-species produced in exhaust ducts and bag filters.

PMID- 20674161
TI  - Zinc oxide particles induce inflammatory responses in vascular endothelial cells
      via NF-kappaB signaling.
AB  - This study investigated inflammatory effects of zinc oxide (ZnO) particles on
      vascular endothelial cells. The effects of 50 and 100-nm ZnO particles on human
      umbilical vein endothelial cells (HUVECs) were characterized by assaying
      cytotoxicity, cell proliferation, and glutathione levels. A marked drop in
      survival rate was observed when ZnO concentration was increased to 45 MUg/ml. ZnO
      concentrations of <=3 MUg/ml resulted in increased cell proliferation, while
      those of <=45 MUg/ml caused dose-dependent increases in oxidized glutathione
      levels. Treatments with ZnO concentrations <=45 MUg/ml were performed to
      determine the expression of intercellular adhesion molecule-1 (ICAM-1) protein,
      an indicator of vascular endothelium inflammation, revealing that ZnO particles
      induced a dose-dependent increase in ICAM-1 expression and marked increases in NF
      kappaB reporter activity. Overexpression of IkappaBalpha completely inhibited ZnO
      induced ICAM-1 expression, suggesting NF-kappaB plays a pivotal role in
      regulation of ZnO-induced inflammation in HUVECs. Additionally, TNF-alpha, a
      typical inflammatory cytokine, induced ICAM-1 expression in an NF-kappaB
      dependent manner, and ZnO synergistically enhanced TNF-alpha-induced ICAM-1
      expression. Both 50 and 100-nm ZnO particles agglomerated to similar size
      distributions. This study reveals an important role for ZnO in modulating
      inflammatory responses of vascular endothelial cells via NF-kappaB signaling,
      which could have important implications for treatments of vascular disease.

PMID- 20674162
TI  - Grain size distribution of road-deposited sediment and its contribution to heavy
      metal pollution in urban runoff in Beijing, China.
AB  - Pollutant washoff from road-deposited sediment (RDS) is an increasing problem
      associated with the rapid urbanization of China that results in urban non-point
      source pollution. Here, we analyzed the RDS grain size distribution and its
      potential impact on heavy metal pollution in urban runoff from impervious
      surfaces of urban villages, colleges and residences, and main traffic roads in
      the Haidian District, Beijing, China. RDS with smaller grain size had a higher
      metal concentration. Specifically, particles with the smallest grain size (<44
      MUm) had the highest metal concentration in most areas (unit: mg/kg): Cd 0.28
      1.31, Cr 57.9-154, Cu 68.1-142, Ni 25.8-78.0, Pb 73.1-222 and Zn 264-664.
      Particles with smaller grain size (<250 MUm) contributed more than 80% of the
      total metal loads in RDS washoff, while suspended solids with a grain size <44
      MUm in runoff water accounted for greater than 70% of the metal mass in the total
      suspended solids (TSS). The heavy metal content in the TSS was 2.21-6.52% of that
      in the RDS. These findings will facilitate our understanding of the importance of
      RDS grain size distribution in heavy metal pollution caused by urban storm
      runoff.

PMID- 20674163
TI  - The comparison of photooxidation processes for the minimization of organic load
      of colored wastewater applying the response surface methodology.
AB  - In this comparative study, the effectiveness of three photooxidation processes
      (UV/H(2)O(2), UV/S(2)O(8)(2-) and UV/O(3)) for degradation of an azo dye model
      pollutant was investigated using several process parameters. The process
      parameters such as initial pH, the concentrations of oxidant in the reactor inlet
      stream and the type of oxidant were considered. In order to investigate the
      influence of cross-factor effects of process parameters, the full factorial
      design was applied with three factors (two numeric and one categorical) at three
      levels combined with response surface modeling. The ANOVA results (R(2), F, p)
      showed high accuracy of developed quadratic model for the zero-order
      mineralization rate constants of AO7 model wastewater. Among process parameters
      studied, the type of oxidant and the concentration of oxidant were shown to be
      the most influential parameters of studied photooxidation processes. The highest
      rate of mineralization of AO7 model wastewater, k(obs)=7.507*10(-7) M s(-1), was
      obtained for UV/O(3) process at the initial pH 10 and oxidant reactor input rate
      of 0.6 mM min(-1). However, when comparing the operating costs for each process
      studied, it was evident that UV/H(2)O(2) process is 1.6 times less expensive than
      UV/O(3) process considering the mineralization of organic content of AO7 model
      wastewater.

PMID- 20674164
TI  - Effect of annealing treatment on the crystallisation and leaching of dumped base
      metal smelter slags.
AB  - Leaching tests of base metals contained in two smelter slags were undertaken in
      ammonia and nitric acid solutions aiming to recover Co, Cu and Zn. Leaching tests
      were conducted at 25 and 60 degrees C at pH=0 and 3 in HNO(3) and pH=12 in
      NH(4)OH media. XRD analysis revealed that the dumped slags were amorphous.
      Annealing these slags at 1180 degrees C produced crystalline phases comprising
      diopside, magnetite and fayalite. SEM and EDS analysis revealed that Cu and Pb
      compounds have concentrated in the magnetite phase, whereas another phase rich in
      Zn and Cu was located in the diopside matrix. ICP-OES analysis of the pregnant
      leaching solutions (PLS) showed that 30-60% of Co, Cu and Zn were released from
      the amorphous slags treated in HNO(3) at pH=0, and lesser in ammonia. However,
      the contamination by Fe and Pb was higher at pH=0. The contamination of the PLS
      obtained by leaching of the crystallised slags remained low. The low Fe and Pb
      contamination was attributed in this case to the chemical stability of the
      crystalline phases formed upon annealing treatment. The higher solubilisation of
      metals contained in amorphous slags was attributed to the collapse of silicate
      structures during nitric acid leaching at pH~0.

PMID- 20674165
TI  - Arsenic content and fractionation in the surface sediments of the Guangzhou
      section of the Pearl River in Southern China.
AB  - The Guangzhou section of the Pearl River (GSPR) has been seriously affected by
      long-term intensive industrial and urban activities. The objectives of this study
      were to determine the total As (TAs) content and the forms of that As in order to
      investigate the geochemical relationships between As forms and sediment mineral
      phases of the surface sediments of the GSPR. Fifteen samples of surface sediment
      were collected and analyzed for TAs as well as As chemical forms. Results
      indicated that TAs in the sediment samples averaged 24.6 mg kg(-1) and ranged
      from 16.7 to 33.4 mg kg(-1). These values are generally higher than the probable
      effect level of 17.0 mg kg(-1). The As was mostly associated with iron oxides
      (53.5%), followed by association with the residual fraction (36.2%). Amor-Fe
      bound As and Cry-Fe bound As quantities were positively correlated to the Amor-Fe
      and Cry-Fe quantities, respectively. In addition, organic matter (OM), clay and
      Sum-Fe contents were positively correlated to TAs in the sediment fractions. The
      molar ratios of iron oxide-bound As to iron content approached the maximum molar
      ratios of As to Fe for natural hematite, magnetite, and goethite. Adverse effects
      caused by As will likely frequently occur at these high levels of As
      contamination. Thus, it is necessary to remediate the sediment of the GSPR to
      reduce the potential risks of As contamination.

PMID- 20674166
TI  - Distribution of 16 EPA-priority polycyclic aromatic hydrocarbons (PAHs) in
      sludges collected from nine Tunisian wastewater treatment plants.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are organic compounds which may be
      present as contaminants in wastewater sewage sludge. Due to their toxicity and
      persistence in the solid phase, information should be gathered relating to their
      presence in sewage sludge in order to determine their contamination risks after
      land application. In this study, sewage sludge samples from nine Tunisian
      wastewater treatment plants (WWTPs) were characterized for the total content in
      16 EPA-priority PAHs using an optimized extraction protocol. These WWTPs differ
      in the type of applied treatment and the wastewater source. Through this first
      assessment of PAHs in Tunisian sludges, their total concentration varied from 96
      to the highest level of 7718 ng g(-1). Regardless of the source of wastewater,
      the highest PAH content was found in sludges deriving from untreated wastewater
      (natural lagooning). In addition, some correlation was found between the
      distribution patterns of each PAH, the type of applied treatment on one hand and
      the wastewater source on other hand.

PMID- 20674167
TI  - Remediation of hexavalent chromium through adsorption by bentonite based
      Arquad(r) 2HT-75 organoclays.
AB  - Unlike hydrophobic organic pollutants, the potential of organoclays to adsorb
      inorganic ionic contaminants is relatively underexplored. The present study
      attempts to characterise bentonite (QB) based organoclays synthesised from a
      commercially available, low-cost alkyl ammonium surfactant Arquad(r) 2HT-75 (Aq)
      and test their ability to adsorb hexavalent chromium (Cr (VI)) in aqueous
      solution. XRD, FTIR and TGA characterisation techniques prove successful
      modification of the bentonite structure and reveal that higher surfactant
      loadings gives rise to more ordered surfactant conformation in the organoclays.
      The zeta potential values indicate that higher surfactant loadings also create
      positive charges on the organoclay surfaces. Detailed isothermal and kinetic
      studies show that the organoclays effectively remove hexavalent chromium (Cr
      (VI)) from aqueous solution by both physical and chemical adsorption processes.
      Higher surfactant loadings provide better adsorption efficiency. The adsorption
      performance is reasonably efficient under the levels of pH, temperature,
      electrolyte concentration and natural organic matter concentration that generally
      prevail in contaminated soil and water. This study shows that organoclay sorbents
      offer good potential for remediating Cr (VI) under real environmental conditions.

PMID- 20674168
TI  - Two-dimensional fuzzy fault tree analysis for chlorine release from a chlor
      alkali industry using expert elicitation.
AB  - The hazards associated with major accident hazard (MAH) industries are fire,
      explosion and toxic gas releases. Of these, toxic gas release is the worst as it
      has the potential to cause extensive fatalities. Qualitative and quantitative
      hazard analyses are essential for the identification and quantification of these
      hazards related to chemical industries. Fault tree analysis (FTA) is an
      established technique in hazard identification. This technique has the advantage
      of being both qualitative and quantitative, if the probabilities and frequencies
      of the basic events are known. This paper outlines the estimation of the
      probability of release of chlorine from storage and filling facility of chlor
      alkali industry using FTA. An attempt has also been made to arrive at the
      probability of chlorine release using expert elicitation and proven fuzzy logic
      technique for Indian conditions. Sensitivity analysis has been done to evaluate
      the percentage contribution of each basic event that could lead to chlorine
      release. Two-dimensional fuzzy fault tree analysis (TDFFTA) has been proposed for
      balancing the hesitation factor involved in expert elicitation.

PMID- 20674169
TI  - Adsorption of methylene blue on raw and MTZ/imogolite hybrid surfaces: effect of
      concentration and calorimetric investigation.
AB  - The synthetic imogolite sample was used for organofunctionalization process with
      2-mercaptothiazoline (MTZ). The compound 2-mercaptothiazoline was anchored onto
      imogolite surface by heterogeneous route. Due to the increment of basic centers
      attached to the pendant chains the dye adsorption capability of the final
      chelating material, was found to be higher than is precursor. The ability of
      these materials to remove methylene blue from aqueous solution was followed by a
      series of adsorption isotherms at room temperature and pH 4.0. The maximum number
      of moles adsorbed was determined to be 40.32*10(-2) and 65.13*10(-2) mmol g(-1)
      for IMO and IMO(MTZ), respectively. The energetic effects caused by dye cations
      adsorption were determined through calorimetric titrations. Thermodynamics
      indicated the existence of favorable conditions for such methylene blue-nitrogen
      and sulfur interactions.

PMID- 20674170
TI  - Comments on "Fluoride removal from water using activated and MnO2-coated tamarind
      fruit (Tamarindus indica) shell: batch and column studies".
AB  - This response comments on the importance and advantage of employing constraint on
      isotherm and kinetic models, for the benefit of young scientific researchers.

PMID- 20674171
TI  - Temporal changes and depth wise variations in pit pond hydrochemistry
      contaminated with industrial effluents with special emphasis on metal
      distribution in water-sediment system.
AB  - The investigation showed pronounced temporal and vertical variations of pit lake
      water chemistry contaminated with industrial effluents. An intermixing layer of
      few meters at a depth of 5-8 m usually separates an upper oxic epilimnion with
      alkaline pH from deeper sub-oxic/anoxic zone with relatively lower pH. Metal
      concentrations were in higher magnitude at anoxic zone in comparison to surface
      layer. Most of the parameters including metals showed higher concentrations
      during summer, while least concentrations were observed during monsoon. In
      shallow sediments, metals were mainly in insoluble-residual form, while redox
      metals were fractionated as oxihydroxide-reducible form. Geoaccumulation of
      metals in bottom sediments were Fe>Cr>Pb>Cu>Cd>Mn>Zn. Toxicity assessment showed
      that pit pond water is highly contaminated (C(d)=7.52) and moderate pollution
      load (PLI=2.272) in shallow sediments, with metal evaluation index (HEI) value of
      11.08 and 15.91 respectively.

PMID- 20674172
TI  - Multiple errors made by authors result in a huge overestimation of potential
      exposure to particles in the size range 10-30 nm in TiO(2) nanoparticle
      production facilities.

PMID- 20674173
TI  - Equilibrium, kinetic and thermodynamic studies on aluminum biosorption by a
      mycelial biomass (Streptomyces rimosus).
AB  - This work focused on kinetic, equilibrium and thermodynamic studies on aluminum
      biosorption by Streptomyces rimosus biomass. Infrared spectroscopy analysis shows
      that S. rimosus present some groups: hydroxyl, methyl, carboxyl, amine, thiol and
      phosphate. The maximum biosorption capacity of S. rimosus biomass was found to be
      11.76 mg g(-1) for the following optimum conditions: particle size, [250-560]
      MUm, pH 4-4.25, biomass content of 25 g L(-1), agitation of 250 rpm and
      temperature of 25  degrees C. Langmuir, Freundlich and Dubinin-Radushkevich (D-R)
      models were applied to describe the biosorption isotherms at free pH (pH(i) 4)
      and fixed pH (pH(f) 4). Langmuir model is the most adequate. With fixed pH, the
      maximum biosorption capacity is enhanced from 6.62 mg g(-1) to 11.76 mg g(-1).
      The thermodynamic parameters (DeltaG degrees , DeltaH degrees  and DeltaS degrees
      ) showed the feasibility, endothermic and spontaneous nature of the biosorption
      at 10-80  degrees C. The activation energy (Ea) was determined as 52.18 kJ mol(
      1) using the Arrhenius equation and the rate constant of pseudo-second-order
      model (the most adequate kinetic model). The mean free energy was calculated as
      12.91 kJ mol(-1) using the D-R isotherm model. The mechanism of Al(III)
      biosorption on S. rimosus could be a chemical ion exchange and carboxyl groups
      are mainly involved in this mechanism.

PMID- 20674174
TI  - e-Health and chronic pain management: current status and developments.

PMID- 20674175
TI  - Changes in undamaged fibers following peripheral nerve injury: a role for TNF
      alpha.

PMID- 20674176
TI  - When does nerve injury hurt?

PMID- 20674177
TI  - Multiplex real-time qPCR for the detection of Ehrlichia canis and Babesia canis
      vogeli.
AB  - Ehrlichia canis and Babesia canis vogeli are two tick-borne canine pathogens with
      a worldwide importance. Both pathogens are transmitted by Rhipicephalus
      sanguineus, the brown dog tick, which has an increasing global distribution. A
      multiplex quantitative real-time PCR (qPCR) assay for the simultaneous detection
      of the tick-borne pathogens E. canis and B. canis vogeli was developed using dual
      labeled probes. The target genes were the 16S rRNA of E. canis and the heat shock
      protein 70 (hsp70) of B. canis vogeli. The canine beta actin (ACTB) gene was used
      as an internal control gene. The assay was conducted without using any pre
      amplification steps such as nested reactions. The sensitivity of each reaction in
      the multiplex qPCR assay was tested in the presence of high template
      concentrations of the other amplified genes in the same tube and in the presence
      of canine DNA. The detection threshold of the multiplex assay was 1-10 copies/MUl
      in all channels and the amplifications of the B. canis hsp70 and ACTB were not
      affected by the other simultaneous reactions, while minor interference was
      observed in the amplification of the E. canis 16S rRNA gene. This assay would be
      useful for diagnostic laboratories and may save time, labor and costs.

PMID- 20674178
TI  - Efficacy, safety and pharmacokinetics of 1,2,4-trioxolane OZ78 against an
      experimental infection with Fasciola hepatica in sheep.
AB  - The synthetic peroxide OZ78 is an effective flukicide in the rodent model, but
      the potential of OZ78 in target animals has not been studied to date. In the
      present study, OZ78 was administered at 50mg/kg orally and subcutaneously to
      sheep harbouring an experimental Fasciola hepatica infection and the efficacy,
      tolerability and pharmacokinetic profiles were monitored. OZ78 given orally or
      subcutaneously revealed no effect neither on faecal egg counts nor on worm
      burdens. Apart from significant subcutaneous swelling at the injection sites of
      most of the treated animals, no other treatment related adverse events occurred.
      OZ78 had no significant effect on any haematological, coagulation or clinical
      chemistry variables tested. Following oral administration, a mean C(max) of
      45.8+/-13 MUg/ml was reached after 1h. An estimated elimination half-life of 1.0
      h and a mean AUC of 116.2+/-47 MUg min/ml was calculated for the oral
      administration. Following subcutaneous treatment with OZ78 C(max) and t(max) were
      13.7+/-6.1MUg/ml and 0.9+/-0.4h, respectively. The alpha and beta half-lives were
      4.5+/-4.3 h and 56.5+/-36 h, respectively and the mean AUC was 219.1+/-74 MUg
      min/ml. Further studies are needed to determine whether the excellent activity
      observed with OZ78 in the rat model can be translated into efficacy in larger
      mammals.

PMID- 20674179
TI  - Aelurostrongylus abstrusus and Troglostrongylus sp. (Nematoda: Metastrongyloidea)
      infections in cats inhabiting Ibiza, Spain.
AB  - Multiple species of metastrongylid lungworm (Nematoda: Metastrongyloidea) have
      been reported to infect members of the Felidae. This study describes two
      metastrongylid species infecting cats in Ibiza, Spain, including clinical
      features of infection and diagnosis via morphological and molecular
      characterisation of larval stages. Cats (n=7) presented with suspect lungworm
      infection, exhibiting coughing and other respiratory signs of infection. Faecal
      samples were collected from each cat and were subjected to the Baermann method
      for the detection of first stage larvae. In four cats, two different species of
      larvae were observed on the basis of morphology and were further molecularly
      characterised by PCR and sequencing of the 18S rRNA gene. Sequence data confirmed
      the presence of Aelurostrongylus abstrusus and an unknown species of
      Troglostrongylus. Molecular characterisation of Oslerus rostratus is also
      reported for the first time. Given the diversity of metastrongylid species
      capable of infecting cats, and morphological similarity of larval stages, an
      emphasis should be placed on the use of molecular characterisation for accurate
      diagnosis of infection.

PMID- 20674180
TI  - Animal models for depression and the mismatch hypothesis of disease.
AB  - Early life stress is one of the best characterized risk factors for psychiatric
      disorders, including depression, and many animal models have therefore studied
      the long-term physiological and behavioural consequences of early life stress. In
      most approaches a very deterministic view of adverse experiences early in life
      prevails, linking these events inevitably with later pathology. By summarizing
      literature on early life programming and adaptive phenotypic plasticity the
      current review proposes that early life challenges may induce changes that
      prepare an individual for life in a more hostile environment and are therefore
      predominantly beneficial. Adult diseases as depression might thus not be promoted
      by early life adversity per se, but by a mismatch of the programmed and the later
      actual environment in combination with a more vulnerable or resilient genetic
      predisposition. The present review further discusses the ability of currently
      available animal models for depression to investigate this novel hypothesis.
      Finally, a number of criteria and research strategies are outlined that would be
      necessary to address the mismatch hypothesis of depression.

PMID- 20674181
TI  - Elevated levels of circulating matrix metalloproteinase-9 are associated with a
      dysregulated cortisol rhythm--A case-control study of coronary artery disease.
AB  - A dysregulated cortisol pattern has been found to be associated with systemic
      inflammatory activity in patients with coronary artery disease (CAD). Matrix
      metalloproteinase (MMP)-9 is involved in both inflammation and matrix degradation
      and considered a main contributor to coronary plaque rupture. In this study, we
      hypothesized that a dysfunctional cortisol response also involved a failure to
      regulate systemic MMP-9 levels in CAD patients. Total MMP-9, active MMP-9 and the
      endogenous inhibitor TIMP-1 were measured in 30 CAD patients and 30 healthy
      controls. Morning and evening cortisol was measured in repeated saliva samples.
      Patients had higher levels of total and active MMP-9 (both p<0.01) and increased
      24-h cortisol output (p<0.05) characterized by higher levels of evening cortisol
      (p=0.011). MMP-9 was associated with evening cortisol (p<0.001) independent of
      smoking and inflammatory markers. Compared with controls, patients also showed a
      blunted cortisol response to stress. After stress, the levels of MMP-9 became
      significantly reduced in controls whereas they remained unchanged in patients.
      The data indicate that MMP-9 is differently regulated in patients due to a
      dysfunctional hypothalamic-pituitary-adrenal (HPA) axis and emphasize the role of
      MMP-9 as a possible link between stress and cardiovascular disease.

PMID- 20674182
TI  - Is serotonin responsible for the relationship between sleep debt and suicide? A
      comment on Kohyama's hypothesis.

PMID- 20674183
TI  - A new hypothesis on the mechanism of digital clubbing secondary to pulmonary
      pathologies.
AB  - Our hypothesis concerns the chronic activation of macrophages, and the continual
      production of pro-fibrotic tissue repair factors, as a cause of digital clubbing
      in an array of pulmonary pathologies. The level of macrophage activation will
      differ between individuals, corresponding to the variable immune response to
      these pulmonary pathologies. Due to this variability, there is a corresponding
      inconsistency in the presentation of clubbing. Although testing of this
      hypothesis would be difficult, there is evidence to support our theory; including
      a link to chronic diseases involving granulomas, where there would be a large
      collection of macrophages present and pathologies in organs with large resident
      macrophage populations. This theory, therefore, could also be developed to
      include non-pulmonary causes of clubbing.

PMID- 20674184
TI  - Do cytokines induce vascular calcification by the mere stimulation of TNAP
      activity?
AB  - Vascular calcification occurs during aging in the general population and is
      increased in the intima by atherosclerosis and in the media by diabetes type 2.
      In both intima and media, calcification may lead to the formation of a tissue
      very similar if not identical to bone, with bone cells and bone marrow. Since
      vascular calcification is associated with cardiovascular complications, a better
      understanding of the inducing mechanisms could lead to the development of new
      therapeutic strategies. Many studies have provided evidence for a role of
      inflammation and inflammatory cytokines such as tumour necrosis factor (TNF)
      alpha and interleukin (IL)-1beta in the vascular calcification process. TNF-alpha
      and IL-1beta have indeed been shown to stimulate in vitro the expression by
      vascular smooth muscle cells (VSMCs) of tissue-non specific alkaline phosphatase
      (TNAP), a key enzyme in the mineralization process, and to trigger the trans
      differentiation of VSMCs into osteoblast-like cells, expressing the master
      transcription factor RUNX2. These data are however somewhat contradictory with
      the known inhibitory effects of inflammatory cytokines on bone formation. TNF
      alpha for instance dramatically decreases RUNX2 RNA expression, protein stability
      and activity, and as a consequence, is a potent inhibitor of osteoblast
      differentiation and bone formation. In the present article, we propose a new
      hypothesis to explain this calcification paradox. We propose that cytokines block
      bone formation by decreasing RUNX2-mediated type I collagen production in
      osteoblasts, whereas they induce vascular ossification by the mere stimulation of
      TNAP by VSMCs, independently of RUNX2. We propose that this stimulation of TNAP
      in VSMCs in vitro and in vivo may be sufficient to induce the calcification of
      collagen fibrils, and that the absence of crystal clearance, in turn, induces the
      differentiation of VSMCs and/or mesenchymal stem cells into bone-forming cells,
      eventually leading to formation of a bone-like tissue. In case future
      experimental studies support this hypothesis, the early stimulatory and late
      inhibitory effects of inflammation on vascular calcification will have to be
      taken into consideration in the development of new therapeutic strategies.

PMID- 20674186
TI  - Altitude, body iron stores, and cancer.

PMID- 20674185
TI  - Oral lichen planus is a unique disease model for studying chronic inflammation
      and oral cancer.
AB  - Oral lichen planus (OLP) is a chronic inflammatory disease, which has been
      defined by the World Health Organization as a potential precancerous condition,
      representing a generalized state associated with a significantly increased risk
      of oral cancer. We would like to put forward a hypothesis that inflammatory
      mediators such as cytokines and chemokines released from infiltrating T
      lymphocytes induce fundamental changes of proteins in oral epithelial cells,
      leading to the progression of OLP to oral squamous cell carcinoma (OSCC). These
      altered proteins can act as the key risk factors associated with the local
      microenvironment and development of OSCC. Identification of these proteins would
      add to our understanding of the connection between chronic inflammation and OSCC.

PMID- 20674187
TI  - Protein denaturing conditions in beef deep semimembranosus muscle results in
      limited MU-calpain activation and protein degradation.
AB  - The objective was to determine the effect of muscle location on protein
      solubility and protein degradation in deep (DSM) and superficial (SSM) portion of
      beef semimembranosus. At 24 h postmortem, the semimembranosus was removed from
      beef carcasses (n=10), packaged in high-oxygen modified atmosphere (80% O2+20%
      CO2), and displayed for 7 d at 1 degrees C. DSM had higher (P<0.05) L*, a*, b*,
      and hue values than SSM throughout display. DSM had significantly higher protein
      denaturation and less protein concentration than SSM. Western blotting for MU
      calpain autolysis revealed that DSM maintained more (P<0.05) unautolyzed MU
      calpain than SSM. This result coincided with less desmin and troponin-T
      degradation in samples from the DSM. These results confirm the hypothesis that
      increased protein denaturation in DSM results in minimal proteolysis by
      negatively affecting MU-calpain activation. This demonstrates a potential to
      alter progression of proteolysis and improvement in tenderness associated with
      postmortem storage.

PMID- 20674188
TI  - Volatile profile and microbiological characterization of hollow defect in dry
      cured ham.
AB  - This paper describes the physicochemical and microbiological parameters and
      volatile profile of the muscles surrounding the coxofemoral joint which are
      affected with hollow defect when compared to the part of muscles nearby which did
      not show this defect. Differences of the same parameters between both areas in
      dry-cured hams without this defect were also analyzed. Gram-positive catalase
      positive cocci were the predominant flora in the muscles affected with hollow
      defect, with the main species being Staphyloccocus equorum, Staphylococcus
      nepalensis and Staphylococcus xylosus. Lactic acid bacteria, Listeria
      monocytogenes and Staphylococcus aureus were <2 log CFU g(-1) and Salmonella spp.
      was not detected. Volatile profile of samples affected with hollow defect had
      higher amounts of compounds such as esters, pyrazines, sulfurs and furans. There
      was a positive correlation between the amount of ester compounds and the hollow
      defect intensity. Moisture content was lower and pH values were higher in
      affected areas than in unaffected areas.

PMID- 20674189
TI  - Importance of DNA damage checkpoints in the pathogenesis of human cancers.
AB  - All forms of life on earth must cope with constant exposure to DNA-damaging
      agents that may promote cancer development. As a biological barrier, known as DNA
      damage response (DDR), cells are provided with both DNA repair mechanisms and
      highly conserved cell cycle checkpoints. The latter are responsible for the
      control of cell cycle phase progression with ATM, ATR, Chk1, and Chk2 as the main
      signaling molecules, thus dealing with both endogenous and exogenous sources of
      DNA damage. As cell cycle checkpoint and also DNA repair genes, such as BRCA1 and
      BRCA2, are frequently mutated, we here discuss their fundamental roles in the
      pathogenesis of human cancers. Importantly, as current evidence also suggests a
      role of MAPK's (mitogen activated protein kinases) in cell cycle checkpoint
      control, we describe in this review both the ATR/ATM-Chk1/Chk2 signaling pathways
      as well as the regulation of cell cycle checkpoints by MAPK's as molecular
      mechanisms in DDR, and how their dysfunction is related to cancer development.
      Moreover, since damage to DNA might be the common underlying mechanism for the
      positive outcome of chemotherapy, we also discuss targeting anticancer treatments
      on cell cycle checkpoints as an important issue emerging in drug discovery.

PMID- 20674190
TI  - Can telomere alterations predict biochemical recurrence in prostate
      adenocarcinoma? A preliminary study.
AB  - Telomeres function in human somatic tissues to stabilize chromosome ends.
      Telomere shortening can be one of the ways that cause chromosomal instability in
      the pathogenesis of prostatic carcinoma. In the current study, we evaluated
      telomere length (TL) in normal and malignant prostate tissues, and its
      association with prognostic factors and with time to biochemical tumor
      recurrence. Tissue microarrays constructed from paraffin blocks from radical
      prostatectomy specimens containing 61 randomly selected cases were used. Sections
      were hybridized with a Cy3-labeled telomere-specific peptide nucleic acid probe.
      TL, proportional to probe fluorescence intensity, was visually evaluated.
      Statistical analysis was done to relate TL clinical and pathological prognostic
      variables. The majority (49/61) of prostate cancers displayed abnormally short
      telomeres. Univariate analysis revealed inverse correlation between telomere
      shortening in tumor and Gleason scores (p=0.017). Multivariate analyses pointed
      to TL as an independent predictor in addition to serum pre-operative PSA for
      reduced biochemical progression-free survival (p=0.035). Telomere shortening is a
      common alteration in prostatic adenocarcinoma. Normal or long telomeres are
      rarely seen and, when present, seem to provide a growth advantage for the tumor
      as being an advocate for poor differentiation.

PMID- 20674191
TI  - Investigation of human papillomavirus in bladder cancer in a series of Tunisian
      patients.
AB  - The association between human papillomavirus (HPV) infection and development of
      bladder cancer is variable. Furthermore, the prevalence of HPV DNA in bladder
      carcinoma subtypes varies from study to study. To clarify the impact of HPV
      infection on the development of bladder carcinoma, we performed a retrospective
      study on Tunisian patients to determine the status of HPV infection in urothelial
      carcinoma, squamous cell carcinoma, and adenocarcinoma. A total of 125 formalin
      fixed, paraffin-embedded archival tissue specimens of bladder carcinoma were
      reviewed and classified according to the World Health Organization (WHO)
      classification of tumors (119 urothelial carcinomas, five squamous carcinomas,
      and one adenocarcinoma). Anogenital HPV DNA detection was performed using three
      different polymerase chain reaction (PCR) techniques: the first one used primers
      pU-2R/pU-1M specific to high-risk oncogenic HPV; the second one used primers PU
      2R/PU-31B specific to low-risk oncogenic HPV; and the third one employed
      consensus primers (E1-547R/E1-350L). No evidence of HPV infection was detected by
      morphological examination and PCR in any case of bladder carcinoma. Our study
      shows that the anogenital HPVs investigated are not associated with the
      pathogenesis of bladder cancer in Tunisia; however, the question of whether other
      subtypes of HPV contribute to bladder carcinogenesis remains to be clarified.

PMID- 20674192
TI  - [Statement: cancer treatments and ovarian reserve].
AB  - PURPOSE OF REVIEW: The purpose of this review is to update the reader on the
      impact of cancer treatment on fertility, the options of fertility preservation,
      and the new markers to assess ovarian function. ESSENTIAL POINTS: The impact of
      chemotherapy and radiotherapy on fertility depends on the drugs and the doses
      used. It often affects ovarian reserve significantly, and the presence of
      menstruation is not a reliable reflection of it. Fertility preservation
      techniques, such as ovarian protection, and preferably cryopreservation combined
      with assisted reproductive medicine, should be individually discussed and
      possibly proposed to the patients. The use of new markers for ovarian reserve
      assessment will help to evaluate infraclinic chemotherapy and/or radiotherapy
      induced effects on ovarian reserve, prior to clinical effects.

PMID- 20674193
TI  - Evaluation of serum VEGF levels in untreated erythrocytosis patients.
AB  - The aim of this prospective study was to investigate the involvement of
      angiogenesis in the etiopathogenesis of the different classes of erythrocytosis
      (polycythemia vera PV, idiopathic erythrocytosis and secondary erythrocytosis).
      The angiogenic activity was evaluated by the assessment of the serum VEGF levels
      in 78 untreated erythrocytosis patients and 21 healthy subjects. The results
      indicated that VEGF was overproduced in advanced and untreated PV patients and at
      less degree, in early PV, a subgroup of idiopathic erythrocytosis, thus
      confirming an increased angiogenic activity. However, VEGF does not play an
      angiogenic role in secondary erythrocytosis.

PMID- 20674194
TI  - Detection and genotyping of GB virus-C in dromedary camels in the United Arab
      Emirates.
AB  - GB virus-C/hepatitis G virus (GBV-C/HGV), collectively known as GBV-C, is widely
      spread and was discovered while searching for a causative agent for non-A-E
      hepatitis. The aim of this study was to determine the rate of infection and
      genotypic characteristics of GBV-C in Arabian camels in the United Arab Emirates
      (UAE). A total of 22 blood and 8 milk samples from healthy camels were screened
      using RT-PCR/nested PCR of the 5'-untranslated region (UTR). Phylogenetic
      analysis was conducted by sequencing the UTR region of randomly picked clones.
      The results obtained showed that the rate of GBV-C infection in camels was 18.2%
      (4 out of 22). All camels milk samples tested negative. Sequence analysis of the
      5'-UTR using isolates from the 4 camels revealed the prevalence of the
      European/North American genotype 2 when compared to the 6 reference genotypes in
      GenBank.

PMID- 20674195
TI  - Transmission of classical swine fever virus depends on the clinical course of
      infection which is associated with high and low levels of virus excretion.
AB  - Infection with moderately virulent strains of classical swine fever virus (CSFV)
      can lead to different courses of disease: either (sub)acute, resulting in death
      or recovery, or chronic disease. The virus excretion dynamics between these
      courses are quite dissimilar, but it is not known if this also results in
      differences in virus transmission. In this study, the excretion and transmission
      dynamics of the moderately virulent Paderborn strain were studied in 15 one-to
      one experiments. In these experiments, a single inoculated pig was housed with a
      single susceptible contact pig from day 1 post-inoculation (p.i.). Each contact
      pig that became infected was removed and replaced by a new contact pig at day 17
      p.i. and day 26 p.i. Infection of contact pigs was monitored by reverse
      transcription quantitative real-time PCR on oropharyngeal fluid samples. Five of
      the inoculated pigs developed the chronic form or died during the acute phase
      (high excreting pigs), while 10 pigs recovered from the infection (low excreting
      pigs). In the first contact period, there was no significant difference in virus
      excretion between the high and low excreting pigs, while in the second and third
      contact period, high excreting pigs excreted significantly higher quantities of
      virus. Over the entire study period, the reproduction ratio differed
      significantly between the high (143 [56.3-373]) and low excreting pigs (23.1
      [11.5-45.0]). This indicates the importance of high excreting pigs in
      transmission of CSFV. Furthermore, this study showed the rate of CSFV infections
      from a contaminated environment.

PMID- 20674196
TI  - Male reproductive tract abnormalities: more common after assisted reproduction?
AB  - BACKGROUND: In this era of increased use of assisted reproduction (AR)
      techniques, the prevalence rates of hypospadias, cryptorchidism, poor semen
      quality have been increasing in parallel with a rising incidence of testicular
      cancer. It is suggested that these problems result from the disruption of gonadal
      development during fetal life causing the testicular dysgenesis syndrome (TDS).
      AIM: The aim of our study was to evaluate the influence of conventional in vitro
      fertilization (IVF) and intracytoplasmic sperm injection (ICSI), on the
      development of male genital tract abnormalities. STUDY DESIGN AND SUBJECTS: We
      analyzed a cohort of 15,206 neonates born from January 1, 1999 through December
      31, 2008 at the Department of Obstetrics and Gynecology, Medical School,
      University of Pecs, including 890 children (5.9%) born after IVF or ICSI. We
      examined the association between these AR methods and developmental abnormalities
      of the genital tract (hypospadias, cryptorchidism), after controlling for
      potential confounding factors, such as prematurity, low birthweight and twinning.
      RESULTS: Preterm birth and low birthweight are risk factors for hypospadias and
      cryptorchidism (p<0.001), twinning increases the risk of hypospadias (p<0.001).
      ICSI was revealed as a risk factor for hypospadias in singletons (OR: 3.190,
      95%CI: 1.266-8.042) and in normal birthweight (>2500 g) infants (OR: 3.966,
      95%CI: 1.193-13.181, respectively). Similar but not nonsignificant trends were
      seen for cryptorchidism. CONCLUSION: IVF and ICSI, by increasing the risks of
      prematurity, low birthweight, and multiple gestation, are indirect risk factors
      for developing male genital malformations. In infants with normal birhtweight or
      from singleton pregnancies, ICSI is a specific risk factor for hypospadias.

PMID- 20674198
TI  - Genetics of the sudden infant death syndrome.
AB  - The sudden infant death syndrome (SIDS) is currently defined as "the sudden
      unexpected death of an infant less than 1 year of age with onset of the fatal
      episode apparently occurring during sleep, that remains unexplained after a
      thorough investigation". SIDS, whose etiology remains rather vague, is still the
      major cause of death among infants between 1 month and 1 year of age in
      industrialized countries with varying incidences in different populations.
      Herein, after touching on definitory approaches and several current hypotheses
      concerning SIDS etiology, we focus on the triple risk model of SIDS and discuss
      two large classes of genetic factors potentially contributing to or predisposing
      for the generation of a vulnerable infant that, when encountering an
      environmental trigger, may succumb to SIDS. We conclude by acknowledging that for
      the integration of the vast and complex genetic evidence concerning SIDS, a lot
      more research will be required and we briefly discuss the potential use of
      recently presented animal models for functional studies of SIDS pathology.

PMID- 20674197
TI  - Antenatal antecedents of a small head circumference at age 24-months post-term
      equivalent in a sample of infants born before the 28th post-menstrual week.
AB  - BACKGROUND: Little is known about the antecedents of microcephaly in early
      childhood among children born at extremely low gestational age. AIM: To identify
      some of the antecedents of microcephaly at age two years among children born
      before the 28th week of gestation. STUDY DESIGN: Observational cohort study.
      SUBJECTS: 1004 infants born before the 28th week of gestation. OUTCOME MEASURES:
      Head circumference Z-scores of <-2 and >or=-2, <-1. RESULTS: Risk of microcephaly
      and a less severely restricted head circumference decreased monotonically with
      increasing gestational age. After adjusting for gestational age and other
      potential confounders, the risk of microcephaly at age 2 years was increased if
      microcephaly was present at birth [odds ratio: 8.8 ((95% confidence interval:
      3.7, 21)], alpha hemolytic Streptococci were recovered from the placenta
      parenchyma [2.9 (1.2, 6.9)], the child was a boy [2.8 (1.6, 4.9)], and the
      child's mother was not married [2.5 (1.5, 4.3)]. Antecedents associated not with
      microcephaly, but with a less extreme reduction in head circumference were
      recovery of Propionibacterium sp from the placenta parenchyma [2.9 (1.5, 5.5)],
      tobacco exposure [2.0 (1.4, 3.0)], and increased syncytial knots in the placenta
      [2.0 (1.2, 3.2)]. CONCLUSIONS: Although microcephaly at birth predicts a small
      head circumference at 2 years among children born much before term, pregnancy and
      maternal characteristics provide supplemental information about the risk of a
      small head circumference years later. Two findings appear to be novel. Tobacco
      exposure during pregnancy, and organisms recovered from the placenta predict
      reduced head circumference at age two years.

PMID- 20674199
TI  - Micro-RNA - A potential for forensic science?
AB  - Micro-RNAs (miRNAs) are a class of small non-coding RNA (ncRNA) molecules with a
      length of 18 to 24 nucleotides which play an essential regulative role for many
      cellular processes. Whereas mRNA-analysis has become a well established technique
      in many forensic laboratories, micro-RNA has only recently been introduced to
      forensic science. Herein we provide a short outline of biogenesis, mode of
      function and regulation of miRNAs and take a look at tissue and cell specific
      miRNA expression. After recapitulating the role of mRNA analysis in forensic
      science we compare it to miRNA analysis and discuss the results of two recent
      studies applying miRNA analysis to a forensic research setting. We conclude that
      analysis of miRNA and perhaps small non-coding RNAs in general clearly has
      potential for forensic applications and merits attention of forensic scientists.

PMID- 20674200
TI  - Resolution of aviation forensic toxicology findings with the aid of DNA
      profiling.
AB  - Body components of aviation accident fatalities are often scattered,
      disintegrated, commingled, contaminated, and/or putrefied at accident scenes.
      These situations may impose difficulties in victim identification/tissue
      matching. The prevalence of misidentification in relation to aviation accident
      forensic toxicology has not been well established. Therefore, the Civil Aerospace
      Medical Institute (CAMI) toxicology database was searched for the 1998-2008
      period for those cases wherein DNA profiling was performed to resolve identity
      issue of the samples submitted to CAMI for toxicological evaluation. During this
      period, biological samples from the casualties of a total of 3523 accidents were
      submitted to CAMI. The submitted samples were primarily from pilots. Out of the
      3523 accidents, at least, one fatality had occurred in 3366 (~ 96%) accidents;
      thus, these accidents were considered fatal accidents. Accordingly, biological
      samples from 3319 pilots (3319 of the 3366 accidents) were received at CAMI for
      toxicological testing. Of these 3319 pilots, 3275 (~ 99%) were fatally injured.
      DNA profiling was performed in 15 (~ 0.5%) of the 3319 accidents. The profiling
      was conducted upon the requests of families in two accidents, accident
      investigators in three, and pathologists in four. In six accidents, contradictory
      toxicological findings led CAMI to initiate DNA profiling. The requests made by
      families and investigators were primarily triggered by inconsistency between the
      toxicological results and the history of drug use of the victims, while by
      pathologists because of commingling of samples. In three (20%) of the 15
      accidents, at least one submitted sample was misidentified or mislabeled. The
      present study demonstrated that the number of aviation accident cases requiring
      DNA profiling was small and this DNA approach was effectively applied in
      resolving aviation toxicology findings associated with those accidents.

PMID- 20674201
TI  - Efficacy of synthetic glue treatment of high crypoglandular fistula-in-ano.
AB  - OBJECTIVES: In France, seton drainage followed by fistulotomy is currently the
      standard treatment for high cryptoglandular fistula-in-ano. Biological or
      synthetic glues, such as Glubran((r)) 2, have been recently proposed for sealing
      the fistula tract. The purpose of this study is to determine the healing rate
      with glubran 2 and to assess the functional outcome after cure of fistula-in-ano.
      PATIENTS AND METHODS: From July 2006 to July 2008, 34 patients (20 males; median
      age 48.5 years, range 22-55 years) with high cryptoglandular anal fistulas were
      treated with glubran 2. Patients were seen for physical examination at 1, 3 and 6
      months, then interviewed by telephone at 1 and 2 years, and in September 2009.
      The Fecal incontinence severity index (FISI) score was used to assess continence.
      RESULTS: The healing rate at 1 month was 67.6% (23 patients); the fistula failed
      to heal in 11 patients. All 23 patients with a healed fistula remained recurrence
      free, with no continence disorders noted, during the median 34-month follow-up
      period (range 21-43 months). One patient was lost to follow-up after 6 months.
      CONCLUSION: Glubran 2 provides an effective treatment for high fistula-in-ano,
      with no change in continence. In future, a randomized comparison of this agent
      with fibrin glues should be useful.

PMID- 20674202
TI  - Liver transplantation for multiple angiomyolipomas complicating tuberous
      sclerosis complex.
AB  - Tuberous sclerosis complex is a genetic multisystem disorder characterised by
      widespread hamartomas in several organs, including the brain, heart, skin, eyes,
      kidney, lung, and liver. Hepatic multiple, bilateral angiomyolipomas are a rare
      and usually asymptomatic complication in patients with tuberous sclerosis. We
      report here the case of a patient who needed liver transplantation because of
      debilitating manifestations and mechanical complications of massive liver
      involvement by multiple angiomyolipomas (severe malnutrition, anorexia and
      abdominal pain). Seventeen tumors, from 2 to 16 cm in diameter, were identified
      at examination of the liver explant. No feature suggestive of malignant behaviour
      was identified at histological examination. In conclusion, this unusual
      indication of liver transplantation underlines the interest of this therapeutic
      approach for benign tumors for which the multiplicity of the lesions and their
      huge volume prevent any attempt at surgical resection.

PMID- 20674203
TI  - Quantitative assessment of perirectal tumor infiltration with dynamic contrast
      enhanced multi-detector row CT in rectal cancer.
AB  - OBJECTIVE: To evaluate the efficacy of discriminant function analysis of
      perirectal tumor infiltration with dynamic contrast-enhanced 64-detector row CT
      in rectal cancer. MATERIALS AND METHODS: Forty-nine patients with rectal cancer
      underwent dynamic contrast-enhanced CT. A total of 96 axial CT slices containing
      the tumors were evaluated. The 96 images were separated into two groups with or
      without perirectal tumor infiltration based on pathological findings. The
      discriminant function was set-up using CT density differences between the mass
      and the adjacent perirectal tissue within 5 mm from the mass at 20 and 40 s as
      independent variables. The results of the discriminant function analysis were
      compared to those of CT morphology and pathology. RESULTS: CT morphological
      diagnosis was accurate on 71.9% (69/96) of the slices with 82.5% sensitivity and
      64.3% specificity. Discriminant function analysis correctly identified 88.5%
      (85/96) of the slices with 85.0% sensitivity and 91.1% specificity. Overstaging
      occurred significantly more (P<0.05) on morphological analysis (20.8%, 20/96)
      than discriminant function analysis (5.2%, 5/96) of the CT slices. CONCLUSIONS:
      Discriminant function analysis of dynamic contrast-enhanced CT improves the
      diagnostic accuracy and specificity of perirectal tumor infiltration in rectal
      cancer.

PMID- 20674204
TI  - High-resolution phase-contrast MRI of aortic and pulmonary blood flow during rest
      and physical exercise using a MRI compatible bicycle ergometer.
AB  - PURPOSE: To establish high-resolution phase-contrast magnetic resonance imaging
      (PC-MRI) using a MRI compatible bicycle ergometer to quantify aortic and
      pulmonary blood flow during resting conditions and exercise. MATERIALS AND
      METHODS: In 20 healthy volunteers (mean age, 26.8+/-5.0 years) high-resolution PC
      MRI (mean temporal resolution, 7.4+/-3.2 ms) was performed in the ascending aorta
      (AA) and main pulmonary artery (PA) during physical rest and three exercise
      stages: stage 1, no-load operation; stage 2, heart rate increase 40% compared to
      rest; stage 3, heart rate increase 80% compared to rest. Flow quantification in
      AA and PA included flow volume (FV), average velocity (AV), peak velocity (PV)
      and time to PV (TP). RESULTS: In stage 1 only TP demonstrated a significant
      change. With progression to stage 2, all parameters altered significantly. Flow
      measurements during stage 3 evidenced further alterations only of AV and TP
      regarding both AA and PA. The deviation of the heart rate from the desired target
      value was significantly higher for stage 3 compared to stage 2, and 15% of the
      subjects did not reach the desired target heart rate of stage 3 at all.
      CONCLUSION: Flow quantification by high-resolution PC-MRI during exercise using a
      MRI compatible bicycle ergometer is feasible. Medium exercise stages are
      necessary and sufficient to demonstrate flow alterations in healthy volunteers.
      PC-MRI ergometry may give insights into aberrant hemodynamic conditions in
      patients with cardiovascular and pulmonary disease.

PMID- 20674206
TI  - Focal ground-glass opacities in non-small cell lung carcinoma resection patients.
AB  - PURPOSE: To retrospectively determine the frequency, natural progression,
      radiographic characteristics, and primary cancer cell type of focal ground-glass
      opacities (GGOs) identified on serial radiographic examinations in patients with
      prior non-small cell lung carcinoma (NSCLC) resection. METHODS: One thousand
      three hundred and seventy-nine CT examinations in 154 patients with NSCLC
      resection between 1997 and 2008 were reviewed by two radiologists to determine
      the frequency of postoperative focal GGOs. Percentages, imaging characteristics
      and primary cancer cell types of GGOs that persisted, resolved, or resected were
      recorded. For persistent GGOs, growth rate was determined. RESULTS: Of 154
      patients, 67 (44%) developed 174 GGO during a mean follow-up of 2.7 years
      (standard deviation 2.23 years, range 1 month to 10 years). Of these 174
      opacities, 110 (63%) spontaneously resolved within 6 months. Of the remaining 64
      lesions, 5 (3%) were resected and 59 (34%) persisted and demonstrated indolent
      growth with a median annual growth rate of 2.02 mm. Of the 59 persistent GGOs, 41
      (69%) were nodularly shaped, 58 (95%) indistinctly marginated, 17 (29%) with
      pseudocavitation and 25 (42%) contained solid elements. Adenocarcinoma was the
      original resected cancer in more than half of these lesions (37 of 59, 63%).
      CONCLUSIONS: In individuals who have undergone NSCLC resection, approximately 44%
      will develop focal GGO on follow-up CT examination. A majority of these GGOs will
      spontaneously resolve by 6 months after initial identification. As most
      persistent GGOs are indolent, we propose an initial 6-month interval reimaging
      once postoperative GGOs are detected followed by subsequent annual surveillance.

PMID- 20674205
TI  - Coronary dual source multi detector computed tomography in patients suspected of
      coronary artery disease: prevalence of incidental extra-cardiac findings.
AB  - OBJECTIVES: (1) To establish the prevalence of incidental extra-cardiac findings
      (ECFs) in coronary multi detector computed tomography (CCT) performed in a large,
      homogeneous cohort of patients suspected of coronary artery disease (CAD). (2) To
      examine whether any association can be established between ECFs and pretest risk
      as determined by conventional risk factors for CAD, the Diamond-Forrester risk
      model or coronary artery calcium scores. (3) To assess cost related to extra
      cardiac examinations. DESIGN: Retrospective study of consecutive patients who had
      CCT performed. A large field of view was recreated from the non-enhanced CT scan
      and evaluated by a radiologist for incidental ECFs. SUBJECTS: Patients with chest
      pain referred to CTA by a cardiologist. RESULTS: In 1383 patients a total of 481
      ECFs were indentified, 378 minor (meaning no follow-up was needed) and 103 major
      ECFs (ECF followed up clinically and/or with additional imaging), in a total of
      393 (28%) patients. 85 (6%) patients had one major ECF and 9 (0.7%) patients had
      two major ECFs. In 19 (4 cases of malignancy) patients the major ECF had
      therapeutic consequences. Significant positive associations were found between
      age and smoking, respectively and the presence of ECFs. The cost estimate of
      saving one life from malignant disease based on ECF examinations is 40,190?.
      CONCLUSION: Incidental extra-cardiac findings are common, sometimes revealing
      serious, even malignant disease. Diagnostic follow-up of major ECFs seems to be
      cost-effective in a Danish clinical setting. We recommend investigating a large
      field of view for incidental ECFs following CCT.

PMID- 20674207
TI  - Radiation protection in medical imaging: a never ending story?

PMID- 20674208
TI  - Analysis of omnoponum by surface-ionization mass spectrometry and liquid
      chromatography tandem mass spectrometry methods.
AB  - This paper provides the development of analytical capabilities of surface
      ionization mass spectrometry (SI/MS) and high performance liquid chromatography
      with tandem mass spectrometry (HPLC/MS/MS) for narcotic analgesic omnoponum,
      which perfectly exemplifies a mixture of opium alkaloids. It has been revealed
      that the investigated opiates solution, omnoponum, is ionized by the surface
      ionization (SI) method with high sensitivity. In the SI mass spectrum, M+, (M
      H)+, (M-H-2nH)+, (M-R)+ and (M-R-2nH)+ ion lines, where M is a molecule, H is the
      hydrogen atom and R is a radical, were observed. These ion lines consist of
      combined omnoponum mixture SI mass spectra, i.e. morphine, codeine, thebaine,
      papaverine, and narcotine. Moreover, while the study of omnoponum by HPLC/MS/MS
      methods has attested that the mixture really consists of 5 components, it has
      been demonstrated that the SI/MS method can be utilized for the analysis of this
      mixture without the necessity of its chromatographic separation.

PMID- 20674209
TI  - Rapid separation and characterization of active flavonolignans of Silybum
      marianum by ultra-performance liquid chromatography coupled with electrospray
      tandem mass spectrometry.
AB  - Ultra-performance liquid chromatography (UPLC) interfaced with the electrospray
      ionization (ESI) tandem mass spectrometer (MS(n)) was developed for the
      simultaneous determination of silychristins A (1) and B (2), silydianin (3),
      silybins A (4) and B (5), and isosilybins A (6) and B (7), major bioactive
      flavonolignans in silymarin, a herbal remedy derived from the milk thistle
      Silybum marianum. In this study, the seven major active flavonolignans including
      the diastereomers 1/2, 4/5, and 6/7 were completely separated using UPLC with an
      ACQUITY UPLC C(18) column and a MeOH/water/formic acid mobile phase system. The
      collision-induced dissociation (CID) MS(n) spectra of these flavonolignans were
      studied systematically using ESI-MS. The results with the present methodology
      show that UPLC-MS(n) can be useful for general screening of active natural
      products from plant extracts and for the specific quality control of silymarin.

PMID- 20674210
TI  - Effect of physical fitness and endurance exercise on indirect biomarkers of
      growth hormone and insulin misuse: Immunoassay-based measurement in urine
      samples.
AB  - Indirect biomarkers of recombinant human growth hormone (rhGH), insulin-like
      growth factor-I (IGF-I), insulin-like growth factor-II (IGF-II), insulin-like
      growth factor binding proteins (IGFBP-2 and IGFBP-3) and insulin (C-peptide) were
      measured together with urinary parameters of renal damage (beta(2)-microglobulin
      and proteinuria) by immunoassays, in house validated for the purpose, in 61
      subjects (36 elite athletes, 18 recreational athletes and 7 sedentary
      individuals) with different levels of physical fitness and endurance exercise.
      Validation parameters were good for the evaluated assays, excluding a high inter
      assay imprecision and inaccuracy of 24 and 26% obtained for GH assay. The range
      of concentrations found in urine samples under investigation was generally
      covered by the calibration curves of the studied immunoassays. However, for the
      samples below or above the calibration curve, opportune dilution or concentration
      were performed. Particularly, C-peptide samples had to be diluted 1:5 and beta(2)
      microglobulin ones assayed using a triple sample volume, to fall within the
      calibration range. Urinary C-peptide was the only biomarker statistically higher
      in samples of elite athletes when compared to recreational athletes and sedentary
      individuals. Among elite athletes, tae-kwon-do athletes showed the highest IGF-II
      basal values while weightlifting athletes showed the lower IGF-I and IGFBP-3
      basal values. The trend observed in weightlifters' basal samples was confirmed in
      their training samples: IGF-I, IGF-II, IGFBP-3 and beta(2)-microglobulin were
      lower in with respect to those from synchronised swimming. Over the training
      season, within athlete variability was observed for IGFBP-3 for weightlifting
      athletes. In the studied subjects, no direct associations were found between
      biomarkers of GH or insulin misuse and urinary parameters of renal damage,
      eventually due to high-workload endurance training. The variations observed in
      different biomarkers should be taken in consideration in the hypothesis of
      setting reference concentration ranges for doping detection.

PMID- 20674212
TI  - Determination of dermatan sulfate and chondroitin sulfate as related substances
      in heparin by capillary electrophoresis.
AB  - Capillary electrophoresis (CE) was applied to the quantitation of dermatan
      sulfate (DS) and chondroitin sulfate (CS) as related substances in sodium
      heparin. The method is based on the selective digestion of either CS and DS
      contained in the main drug heparin, by using chondroitinase ABC (specific for
      both DS and CS) and chondroitinase AC (specific for only CS). The unsaturated
      disaccharides released after exhaustive digestion, can be separated by CE using a
      110mM phosphate buffer, pH 3.5 as the background electrolyte in a fused silica
      capillary (64.5cmx50mum i.d.) at 40 degrees C and -30kV. Since the level of each
      disaccharide released upon enzymatic digestion corresponds to its content in the
      native glycosaminoglycan, the amount of CS and DS was determined by proportion
      with the released disaccharides. In particular, DeltaUA-->GalNAc-4S Na(2) and
      DeltaUA-->GalNAc-6S Na(2) were selected for quantitation of CS and DS because of
      their significant response and short migration time (less than 7min).The method
      was validated for linearity, accuracy, precision and it showed to be able in
      detecting selectively, DS and CS at impurity level (LOD 0.01%, w/w). The proposed
      CE approach was finally applied to real samples. The results obtained were found
      in excellent correlation with those achieved by the analysis of the same samples
      using the official USP method based on high performance anion exchange
      chromatography (HPAEC) with pulsed amperometric detector.

PMID- 20674211
TI  - New coated SPME fibers for extraction and fast HPLC determination of selected
      drugs in human blood.
AB  - Polythiophene (PTh) and polypyrrole (PPy) as sorbent phases for solid phase
      microextraction (SPME) were applied in order to extract the multi-resistant
      Staphylococcus aureus (MRSA) antibiotic drugs (linezolid and daptomycin) from
      whole blood followed by high performance liquid chromatography (HPLC)
      determination with UV detection. Relative standard deviations (RSDs) of in vitro
      and pseudo in vivo measurements performed in whole blood were in the range of
      4.58-15.91% and 6.09-17.33% for linezolid and daptomycin, respectively.
      Determination coefficients (R(2)) were in range of 0.9884-0.9945 and 0.9807
      0.9818 for linezolid and daptomycin, respectively. This study proved better
      adsorption capacity of PTh SPME coating compared to PPy coating for both,
      linezolid and daptomycin.

PMID- 20674213
TI  - Quantitative determination of sirolimus in dog blood using liquid chromatography
      tandem mass spectrometry, and its applications to pharmacokinetic studies.
AB  - A rapid, sensitive method of detecting sirolimus in blood was developed and
      applied in pharmacokinetic studies employing deionized water for hemolysis and a
      weakly basic mobile phase to enhance chromatographic peak intensity. Dog blood
      samples were processed via liquid-liquid extraction and the amounts of sirolimus
      and tacrolimus, an internal standard, were quantified by LC-MS/MS. Specificity,
      the lower limit of quantification, linearity, accuracy, precision, dilution,
      recovery, matrix effects, robustness and stability were within the acceptable
      range for assay validation. The concentration of sirolimus was quantifiable in
      blood samples for up to 36 h after the dog had received a 3 mg/kg dose of
      sirolimus. These observations suggest that sirolimus can be detected at low
      levels in dog blood using a basic mobile phase and metal-free hemolysis. This
      method is therefore applicable to pharmacokinetic studies in dogs.

PMID- 20674214
TI  - Using Raman spectroscopy in tablet moisture surface analysis: tablet surface
      markers.
AB  - A method was developed to monitor the hydration of a tablet surface using
      chemical functional groups able to bind atmospheric water through H-bonding. In
      this study, generic oral dissolving loratadine tablets were used. These tablets
      have relatively high mannitol and lactose concentrations. Both mannitol and
      lactose have C-OH alcohol functional groups, several of which are potentially
      available for H-bonding with atmospheric water. The Raman intensity of the
      alcohol functional groups decreases upon hydration. This observation can be used
      to indirectly monitor water adsorbed to tablet surfaces at the alcohol sites. The
      hydration assay is based on the change in the Raman peak intensity of the alcohol
      C-OH stretching at 875.5 cm(-1). Consequently the decrease in the Raman intensity
      of this vibration can be used to monitor water adsorption. The Raman measurement
      of tablet surface water was compared to the direct moisture measurement method
      using a microbalance. The Raman spectroscopy is used to monitor the water that is
      specifically bound to the C-OH alcohol functional groups available for hydration.
      The microbalance was used to monitor the tablets' weight change during water
      adsorption and desorption. The distribution of the ratio of the Raman intensity
      of C-OH peak at 875.5 cm(-1) divided by the intensity of loratadine's C-Cl peak
      at 712.6 cm(-1) was experimentally determined to be a Gaussian distribution with
      a mean of 3.22+/-0.277. Raman analysis indicates that there is both tightly and
      loosely bound water at the tablet surface. This can be a useful technique with
      regard to inspecting and controlling the tablet drying process.

PMID- 20674215
TI  - Evaluation of the Architect tacrolimus assay in kidney, liver, and heart
      transplant recipients.
AB  - The narrow therapeutic range of tacrolimus requires therapeutic drug monitoring
      to prevent transplant rejection and to minimize nephrotoxicity. The aim of this
      study was to evaluate the analytical performance of the tacrolimus
      chemiluminescent microparticle immunoassay (CMIA) in everyday practice
      comparatively with other methods. CMIA imprecision and accuracy were tested using
      low, medium, and high concentrations in control samples. The limits of
      quantification (LOQ) of CMIA and antibody-conjugated magnetic immunoassay (ACMIA)
      were evaluated using negative whole-blood samples containing 0.4-5.7 ng/ml of
      tacrolimus from a stock solution. CMIA was compared with ACMIA, enzyme multiplied
      immunoassay (EMIT), and liquid chromatography-tandem mass spectrometry (LC
      MS/MS), using 176 samples from recipients (135 men and 41 women) of heart (n=19),
      kidney (n=107), or liver (n=50) transplants. CMIA total precision was 5.7%, 3.7%
      and 3.6% with the low-, medium-, and high-concentration controls, respectively;
      corresponding values for accuracy were 98%, 104%, and 104%. LOQ was 0.5 (95%CI,
      0.22-1.38) with CMIA and 2.5 ng/ml with ACMIA. Linear regression results were as
      follows: CMIA=1.2LC-MS/MS+0.14 (r=0.98); CMIA=0.93EMIT+0.36 (r=0.975);
      CMIA=1.15ACMIA-0.25 (r=0.988); and, for tacrolimus concentrations in the 1-15
      ng/ml range, of special interest as many transplant recipients are given low-dose
      tacrolimus, CMIA=1.05LC-MS/MS+0.38 (r=0.94). Two patients had falsely elevated
      tacrolimus concentrations due to interference in the ACMIA assay; one was a renal
      transplant recipient who stopped her treatment and had tacrolimus concentrations
      of 12.5 ng/ml by ACMIA and <0.5 ng/ml by CMIA; the other was an HIV-positive
      renal transplant recipient whose tacrolimus concentrations by ACMIA were 1.8-43.7
      fold those by CMIA. Such interferences with ACMIA, which may be related to
      endogenous antibodies in the plasma, are likely to negatively impact patient
      care. In conclusion, the tacrolimus CMIA assay is suitable for routine laboratory
      use and does not suffer from the interferences seen with ACMIA in some patients.

PMID- 20674216
TI  - Capillary electrophoresis--mass spectrometry: recent trends in clinical
      proteomics.
AB  - The increasing attention now paid to the elucidation of human proteome
      strengthened the development of analytical instruments able to provide reliable
      proteins and peptides quantitation and characterization in biological fluids and
      tissues. Emerging from proteomics, clinical proteomics exclusively considers its
      biomedical applications. It evaluates, often by high-throughput comparative
      platforms, the protein and peptide variations in body fluids, cells and tissues
      under different physiological and pathological conditions with the aim of
      discovering disease biomarkers. Among the available analytical methodologies,
      mass spectrometry in coupling with liquid chromatography or capillary
      electrophoresis demonstrated to be the eligible technique for protein detection
      and identification. This review summarizes the most recent applications of
      capillary electrophoresis-mass spectrometry to clinical proteomics, focusing on
      capillary zone electrophoresis separation mode and ESI and MALDI ionizations,
      which are the most frequently applied capillary electrophoresis-mass spectrometry
      hyphenated techniques.

PMID- 20674217
TI  - Calorimetric determination of dissolution enthalpy with a novel flow-through
      method.
AB  - A new calorimetric flow-through system for determining the enthalpies of
      dissolution with small amount of solids (<1mg) was developed. The system was
      designed to be used as an add-on cell with a 4 ml twin heat conduction
      calorimeter 2277 TAM but the principle is adoptable also for other heat
      conduction calorimeters. The system was tested with two salts (NaCl, KCl),
      sucrose and different polymorphic forms of theophylline at 25 degrees C and 40
      degrees C by using water as the solvent. The system gave more accurate and
      precise results at 25 degrees C. The precision was not affected by the extent of
      the dissolution enthalpy. The accuracy was dependent on the calibration utilized
      but even the normal electrical calibration gave acceptable values. The results
      obtained at 40 degrees C were also acceptable but not as good as at 25 degrees C
      due to heat leaks. The effect of heat leaks can be minimized by heating the
      inflowing solvent outside the calorimeter prior to entering the flow-through
      cell.

PMID- 20674218
TI  - Proteomic study of serum proteins in a type 2 diabetes mellitus rat model by
      Chinese traditional medicine Tianqi Jiangtang Capsule administration.
AB  - Proteomics technology was for the first time applied to investigate the changes
      of serum proteins levels in type 2 diabetes mellitus (T2DM) rat model after
      treated by Chinese traditional medicine Tianqi Jiangtang Capsule (ten normal
      Wistar rats, ten with T2DM and ten with T2DM administrated by Tianqi Jiangtang
      Capsule). In addition to two-dimensional polyacrylamide gel electrophoresis (2
      DE), serum protein profiling in the three groups was further performed using
      matrix-assisted laser desorption/ionization mass spectrometry (MALDI-TOF-TOF/MS).
      11 visualized spots were differentially regulated and identified as diabetes
      associated proteins. All the samples in three groups were then analyzed by ELISA
      and estimated the 7 proteins which were found to vary. The distinct effect of
      T2DM induction on the pattern of rat serum includes the down-regulation of
      Apolipoprotein E, Apolipoprotein A-I, Ig gamma-2A chain C region, and up
      regulation of Transthyretin (TTR), Haptoglobin (Hp), Serum amyloid P-componen
      (SAP), Prothrombin. The majority of those protein levels were interestingly
      restored to those of healthy rats after Tianqi Jiangtang Capsule treatment.

PMID- 20674219
TI  - Etiology of septic arthritis in children: an update for the new millennium.
AB  - OBJECTIVE: We sought to describe the causative organisms and joints involved in
      cases of pediatric septic arthritis in the post-Haemophilus influenzae type B and
      post-pneumococcal vaccine age and in the age of increasing infection with
      community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA).
      METHODS: This was a retrospective chart review of all children younger than 13
      years presenting to our tertiary care pediatric emergency department between
      January 1, 2003, and December 31, 2007, with the diagnosis of septic arthritis.
      We reviewed the results of synovial fluid Gram stain and synovial fluid and blood
      culture. We defined septic arthritis as any of these 3 tests being positive for a
      known pathogen. We report patient characteristics, joint(s) involved, and
      organisms identified in these cases. RESULTS: We describe 13 cases of septic
      arthritis. Fifteen joints were involved. The most common joint involved was the
      hip (6/15) followed by the elbow (3/15), knee (2/15), and ankle (2/15). The most
      common organism involved was methicillin-sensitive S aureus (6/13), followed by
      CA-MRSA (2/13) and Streptococcus pneumoniae (2/13). CONCLUSION: Our results
      support continued concern for involvement of the hip and knee in cases of
      pediatric septic arthritis and consideration of other joints such as the elbow.
      Our data also suggest that empiric antibiotic coverage for CA-MRSA is indicated
      in cases of pediatric septic arthritis, as well as continued coverage for
      methicillin-sensitive S aureus and S pneumoniae.

PMID- 20674220
TI  - Acute episode of reversible blindness after an overdose of beta blockers and
      calcium channel antagonist.

PMID- 20674221
TI  - Using appendicitis scores in the pediatric ED.
AB  - STUDY OBJECTIVE: The aims of the study were to prospectively evaluate the
      Alvarado and Samuel (pediatric appendicitis score [PAS]) appendicitis scoring
      systems in children and determine performance based on sex. METHODS: Children
      with abdominal pain concerning for appendicitis were recruited. Nine parameters
      evaluated by the scores were documented before imaging/surgery consultation. Test
      characteristics were calculated on all patients and by sex. RESULTS: Two hundred
      eighty-seven patients enrolled; median age was 9.8 years; and 155 (54%) were
      diagnosed with pathologic examination-confirmed appendicitis. Patients with
      appendicitis had mean PAS of 7.6, and those without had mean of 5.6 (P < .001).
      Patients with appendicitis had a mean Alvarado of 7.2, and those without had a
      mean of 5.2 (P < .001). In appendicitis patients, PAS cutoff of 6 or greater
      would give 137 correct diagnoses; sensitivity, 88%; specificity, 50%; and
      positive predictive value (PPV), 67%. An Alvarado cutoff of 7 or greater would
      give 118 correct diagnoses; sensitivity, 76%; specificity, 72%; and PPV, 76%.
      Both performed better in males than females. CONCLUSION: Regardless of sex,
      neither PAS nor Alvarado has adequate predictive values for sole use to diagnose
      appendicitis.

PMID- 20674222
TI  - Complications of percutaneous procedures.
AB  - Minimally invasive percutaneous procedures are increasingly being performed by
      both interventional radiologists and noninterventionalists. Patients with
      postprocedural issues will likely present to the emergency department for
      evaluation and treatment. This review focuses on the evaluation and management of
      the complications of common percutaneous procedures.

PMID- 20674223
TI  - Methadone-induced torsade de pointes.

PMID- 20674224
TI  - Do modern conflicts create different medical needs?
AB  - PURPOSES: This study involved analysis of (a) type of injuries and medical
      services used by military casualties in 3 conflicts and (b) medical needs of
      military and civilian casualties from the 2006 conflict. BASIC PROCEDURES:
      Military casualties from 3 conflicts and military and civilian casualties from
      the 2006 conflict were analyzed. Casualties were compared in relation to type of
      injury, length of stay (LOS), and operating room use (ORU). MAIN FINDINGS:
      Hospital LOS of soldiers in many departments decreased while increasing in
      intensive care unit (ICU). Type of injuries sustained by civilians and military
      casualties differed significantly. More civilian casualties required admission to
      ICU. Civilian ORU was higher for orthopedic and otolaryngological procedures.
      PRINCIPAL CONCLUSIONS: Civilians are less well protected during military
      conflicts, therefore, more susceptible to certain kind of injuries. Civilian and
      military casualties during conflicts have different medical needs. Civilians have
      higher morbidity than soldiers, which result in an increased need for treatment
      in ICU.

PMID- 20674225
TI  - In flight auscultation: comparison of electronic and conventional stethoscopes.
AB  - OBJECTIVES: The ability to auscultate during air medical transport is compromised
      by high ambient noise levels. The aim of this study was to assess the
      capabilities of a traditional and an amplified stethoscope (which is expected to
      reduce background and ambient noise) to assess heart and breath sounds during
      medical transport in a Falcon 50 plane. METHODS: A prospective, double-blind,
      randomized study was performed. We tested 1 model of traditional stethoscope
      (Littman cardiology III) and 1 model of amplified stethoscope (Littman 3100). We
      studied heart and lung auscultation during real medical evacuations aboard Falcon
      50 (medically configured). For each, the quality of auscultation was described
      using a numeric rating scale (ranging from 0 to 10, with 0 corresponding to "I
      hear nothing" and 10 corresponding to "I hear perfectly"). Comparisons were
      accomplished using a t test for paired values. RESULTS: A total of 32 comparative
      evaluations were performed. For cardiac auscultation, the value of the rating
      scale was 5.8 +/- 1.5 and 6.4 +/- 1.9, respectively, for the traditional and
      amplified stethoscope (P = .018). For lung sounds, quality of auscultation was
      estimated at 3.3 +/- 2.4 for traditional stethoscope and at 3.7 +/- 2.9 for
      amplified stethoscope (P = .15). CONCLUSIONS: Practicians in Falcon 50 are more
      able to hear cardiac sounds with an amplified than with a traditional
      stethoscope, whereas there is no significant difference concerning breath sounds
      auscultation.

PMID- 20674226
TI  - Extra scrotal spermatocele causing lower abdominal pain: a first case report.
AB  - Lower quadrant abdominal pain is a common complaint evaluated in emergency
      departments (EDs). The number of differential diagnoses is lowered when the pain
      in a male patient is associated with a palpable tender mass. These diagnoses
      include inguinal hernia, inflamed inguinal lymph node, rectus sheath hematoma,
      cryptorchidism, mass derived from the spermatic cord, and polyorchidism. We
      report a case of extra scrotal spermatocele causing lower quadrant abdominal pain
      that was misdiagnosed as an inguinal hernia on several ED visits. Lower quadrant
      mass and pain caused by a spermatocele are unusual conditions. Upon the patient's
      third (ED) visit, the painful mass remained located in his right lower quadrant.
      The lower quadrant mass was movable on palpation and with pressure could be
      delivered into the superior aspect of the scrotum. The patient had an abdominal
      and pelvic computed tomography scan and lower quadrant ultrasound. The imaging
      studies revealed the mass to be a cystic structure. Surgical excision confirmed
      that the mass was a spermatocele. Differential diagnoses, diagnostic approaches,
      and treatment are discussed.

PMID- 20674227
TI  - Incomplete documentation of elements of Ottawa Ankle Rules despite an electronic
      medical record.
AB  - PURPOSE: The purpose of the study was to observe the frequency of complete
      documentation of the elements of the Ottawa Ankle Rules (OAR) in acute foot and
      ankle injuries in an emergency department with an electronic medical record.
      PROCEDURE: Seven hundred patient visits for acute ankle/foot injuries were
      reviewed. Each component of the OAR was tabulated as positive, negative, or not
      documented. Radiograph ordering and results were collected. Descriptive
      statistics were calculated. MAIN FINDINGS: Of the 700 charts evaluated, 663
      received a radiograph, with 138 fractures identified. The OAR components were
      completely documented in 288 subjects (41%; 95% confidence interval, 37%-45%).
      One hundred percent of the charts documented weight-bearing status (template
      provided), but less than 0.5% (n = 3) documented a navicular examination (not
      mentioned on the template). CONCLUSION: Incomplete documentation of examination
      components is common, even with prompting from an electronic medical record. This
      engenders both medicolegal risk and an inability to perform quality analyses to
      minimize unnecessary radiograph use.

PMID- 20674228
TI  - A 24-year-old woman with neck pain.

PMID- 20674229
TI  - Severe carbon monoxide poisoning complicated by hypothermia: a case report.
AB  - It is proposed that the significant elevation of interleukin-6 (>400 pg/mL) in
      cerebrospinal fluid during the early phase of carbon monoxide poisoning may be a
      predictive biomarker for the development of delayed encephalopathy. A 52-year-old
      man presented to the emergency department with severe carbon monoxide poisoning.
      On arrival, the patient was comatose with decorticate rigidity (Glasgow Coma
      Scale, E1V1M3). His core body temperature, measured in the urinary bladder, was
      32.4 degrees C. Laboratory blood analysis revealed elevated CO-Hb (36.0%) and
      metabolic acidosis with elevated lactate (pH 7.081; base excess [BE], -19.2
      mmol/L; HCO3, -9.8 mmol/L; lactate, 168.8 mg/dL). After treatment with hyperbaric
      oxygen and several different rewarming techniques, he became alert and his core
      body temperature increased to normal. Interleukin-6 in cerebrospinal fluid at 5.5
      hours after his last exposure to carbon monoxide was significantly elevated (752
      pg/mL). However, he did not develop delayed encephalopathy. In this case,
      hypothermia in the range of therapeutic hypothermia (32 degrees C to 34 degrees
      C) may have suppressed formation of reactive oxygen species and subsequent lipid
      peroxydation, preventing the development of delayed encephalopathy. Therapeutic
      hypothermia initiated soon after the last exposure to carbon monoxide may be an
      effective prophylactic method for preventing the development of delayed
      encephalopathy.

PMID- 20674230
TI  - Idiopathic purpura fulminans.

PMID- 20674231
TI  - Thrombolysis associated with LUCAS (Lund University Cardiopulmonary Assist
      System) as treatment of valve thrombosis resulting in cardiac arrest.

PMID- 20674232
TI  - Computed tomography scanning during a traumatic resuscitation.

PMID- 20674233
TI  - Wunderlich syndrome: an unusual cause of flank pain.

PMID- 20674234
TI  - A case of closed total dislocation of talus and literature review.

PMID- 20674235
TI  - Use of inhaled nitric oxide in the treatment of right ventricular myocardial
      infarction.

PMID- 20674236
TI  - Bedside ultrasonography as a safe and effective tool to diagnose acute
      epiglottitis.
AB  - Acute epiglottitis is a true airway emergency in the emergency department (ED).
      The patient may appear very toxic and rapidly progress to respiratory distress
      and life-threatening condition. The inflammatory process includes not only
      epiglottis but also the rest of the supraglottic area including the vallecula,
      aryepiglottic folds, and arytenoids. Soft tissue swelling over this windpipe area
      can be very dramatic. The criterion standard of diagnosis is direct inspection of
      cherry red and swollen epiglottis by laryngoscopy in the operation room with
      immediate access to anesthetists or ear, nose, and throat specialists. However,
      before the patients are well prepared, the clinical condition may critically go
      downhill; and any intention to visualize the throat can result in severe and
      fatal airway spasm. Thumbprint sign on lateral radiography of neck is typical,
      but it may be extremely risky to let a patient leave the consulting room for the
      study if respiratory distress has developed. We demonstrate a safe and practical
      way to investigate the epiglottis by bedside ultrasonography to visualize the
      "alphabet P sign" in a longitudinal view through thyrohyoid membrane by emergency
      physician in the ED.

PMID- 20674237
TI  - Low yield of ED magnetic resonance imaging for suspected epidural abscess.
AB  - PURPOSE: The aim of this study was to estimate the yield of emergency department
      (ED) magnetic resonance imaging (MRI) in detecting spinal epidural abscess (SEA)
      and to identify clinical factors predicting positive MRI results. BASIC
      PROCEDURE: We examined a cohort of patients who underwent MRI to rule out SEA,
      followed by a nested case-control comparison of those with positive results and a
      sample with negative results. A positive result was defined as osteomyelitis,
      discitis, or SEA. Predictor variables included temperature, presenting complaint,
      drug abuse status, history of SEA or back surgery, midline back tenderness,
      neurologic deficit, MRI level, mean white blood cell count, erythrocyte
      sedimentation rate, and C-reactive protein level. MAIN FINDINGS: Fourteen of the
      120 available MRIs were excluded; 7 (6.6%) of the remaining 106 were positive.
      Temperature was 1.1 degrees C higher in cases than controls (95% CI, 0.6-1.7).
      CONCLUSION: Emergency department MRI for suspected SEA has a low yield. Clinical
      guidelines are needed to improve efficiency.

PMID- 20674238
TI  - Inadequacy of temperature and white blood cell count in predicting bacteremia in
      patients with suspected infection.
AB  - BACKGROUND: Early treatment of sepsis in Emergency Department (ED) patients has
      lead to improved outcomes, making early identification of the disease essential.
      The presence of systemic inflammatory response criteria aids in recognition of
      infection, although the reliability of these markers is variable. STUDY
      OBJECTIVE: This study aims to quantify the ability of abnormal temperature, white
      blood cell (WBC) count, and bandemia to identify bacteremia in ED patients with
      suspected infection. METHODS: This was a post hoc analysis of data collected for
      a prospective, observational, cohort study. Consecutive adult (age >= 18 years)
      patients who presented to the ED of a tertiary care center between February 1,
      2000 and February 1, 2001 and had blood cultures obtained in the ED or within 3 h
      of admission were enrolled. Patients with bacteremia were identified and charts
      were reviewed for presence of normal temperature (36.1-38 degrees C/97-100.4
      degrees F), normal WBC (4-12 K/MUL), and presence of bandemia (> 5% of WBC
      differential). RESULTS: There were 3563 patients enrolled; 289 patients (8.1%)
      had positive blood cultures. Among patients with positive blood cultures, 33% had
      a normal body temperature and 52% had a normal WBC count. Bandemia was present in
      80% of culture-positive patients with a normal temperature and 79% of culture
      positive patients with a normal WBC count. Fifty-two (17.4%) patients with
      positive blood cultures had neither an abnormal temperature nor an abnormal WBC.
      CONCLUSION: A significant percentage of ED patients with blood culture-proven
      bacteremia have a normal temperature and WBC count upon presentation. Bandemia
      may be a useful clue for identifying occult bacteremia.

PMID- 20674239
TI  - Evaluating an intervention to increase cancer knowledge in racially diverse
      communities in South Carolina.
AB  - OBJECTIVE: To conduct a cancer education intervention with racially diverse
      communities in South Carolina. METHODS: The study was conducted at eight
      different sites in six counties in SC. The intervention included a 3-h general
      cancer knowledge and 30-min prostate cancer knowledge component. Pre- and post
      intervention surveys were administered. Maximum scores were 31, 10 and 5 for the
      general cancer knowledge, prostate cancer knowledge and perceived self-efficacy
      in patient-physician interaction instruments, respectively. Analyses were
      completed using SPSS 16.0, SAS 9.1.3, and R v2.6.1. RESULTS: The study sample
      consisted of 164 predominantly African American participants. Most of the
      participants who reported age were 50+ years (62.5%). Among those who reported
      income, 46.1% had an annual household income <$40,000. The mean general cancer
      knowledge pre-test score was 26.2 (standard deviation (SD) 3.7) with a mean post
      intervention increase of 2.15 points (p<0.01). The mean pre-test prostate cancer
      knowledge score was 7.3 (SD 2.0) with a post-intervention increase of 0.48 points
      (p<0.01). Perceived self-efficacy in patient-physician interaction scores had a
      ceiling effect. CONCLUSION: General cancer knowledge and prostate cancer
      knowledge scores increased following the intervention. PRACTICE IMPLICATIONS: The
      intervention was successful in the short-term. It could be continued by community
      members.

PMID- 20674240
TI  - Following the clues: teaching medical students to explore patients' contexts.
AB  - OBJECTIVE: Physicians often overlook important contextual clues that patients
      give during an encounter. The objective of our study was to increase medical
      students' knowledge and skills in identifying contextual issues. METHODS: Six
      consecutive learning experiences, including a standardized patient (SP) encounter
      and activities designed to trigger reflection, were implemented within a first
      year Introduction to Clinical Medicine course. Evaluation of the intervention was
      measured through self-confidence, attitudes, SP history checklist, and student
      and small group facilitator evaluations. RESULTS: Standardized patient
      encounters, coupled with activities designed to trigger reflection, can help
      students identify patients' contextual clues. Students' confidence in eliciting
      patient clues significantly increased after the intervention. Our results suggest
      that some contextual clues were more difficult for students to elicit.
      CONCLUSION: Multi-faceted approaches that include activities to trigger
      reflection are effective in teaching students to recognize and respond to
      contextual clues, however, more research is needed. PRACTICE IMPLICATIONS: While
      students elicited most clues in this study, they struggled with identifying some
      clues. These results suggest the need for additional research and educational
      development in this area.

PMID- 20674241
TI  - Recovery at work: the relationship between social identity and commitment among
      substance abuse counselors.
AB  - The complex makeup of the substance abuse treatment workforce poses unique
      challenges to the field. One interesting dynamic is the high rate of counselors
      who are personally recovering from addictions. Based on social identity theory,
      it was expected that counselors working in the field of substance abuse treatment
      who are in recovery themselves will identify more with their profession and
      report higher professional and organizational commitment. Data from a study of
      substance abuse counselors from across the United States support the proposed
      relationship between personal recovery status and professional commitment but not
      organizational commitment.

PMID- 20674242
TI  - Warfarin anticoagulation before angioplasty relieves thrombus burden in Budd
      Chiari syndrome caused by inferior vena cava anatomic obstruction.
AB  - OBJECTIVES: Pulmonary embolism (PE) is one of the major complications after
      percutaneous balloon angioplasty (PTBA) for Budd-Chiari's syndrome (BCS). The
      purpose of this study was to investigate the role of warfarin pre-treatment in
      the prevention of PE after PTBA in patients with large inferior vena cava (IVC)
      thrombus. PATIENTS AND METHODS: From October 2002 to December 2009, 16 patients
      with symptomatic membranous or segmental IVC occlusion and large thrombus were
      treated with warfarin before PTBA. Eleven patients were men and 5 were women. The
      median age was 36 years, ranging from 21 to 52 years. The median duration of
      warfarin treatment before PTBA was 7 months, ranging from 3 to 12 months.
      Fourteen patients had membranous IVC occlusion and 2 had segmental occlusion. All
      16 patients had significant thrombi underneath the obstructive lesions. PE
      diagnosis was based on clinical presentation and pulmonary computerized
      tomographic angiogram, if indicated. RESULTS: In 14 of 16 patients, IVC thrombus
      was completely or near-completely resolved based on follow-up cavogram and PTBA
      was performed. In the other 2 patients, residual thrombus was demonstrated by
      cavogram at 12 months. PTBA and stent placement were carried out. IVC patency in
      the 16 patients was confirmed by completion cavogram. No major bleeding
      complication during warfarin pre-treatment aimed to keep international normalized
      ratio (INR) 2 to 3. There was no clinically significant PE or death in this group
      during follow-up, ranging from 6 to 40 months (median 21 months). CONCLUSION:
      Spontaneous fibrinolysis of IVC thrombus occurs within 1 year in the majority of
      the patients treated with warfarin. Pre-treatment with warfarin prevents PE after
      PTBA in the patients with BCS with IVC membranous or segmental occlusion and
      large thrombus.

PMID- 20674243
TI  - Incorporating simulation in vascular surgery education.
AB  - The traditional apprenticeship model introduced by Halsted of "learning by doing"
      may just not be valid in the modern practice of vascular surgery. The model is
      often criticized for being somewhat unstructured because a resident's experience
      is based on what comes through the "door." In an attempt to promote uniformity of
      training, multiple national organizations are currently delineating standard
      curricula for each trainee to govern the knowledge and cases required in a
      vascular residency. However, the outcomes are anything but uniform. This means
      that we graduate vascular specialists with a surprisingly wide spectrum of
      abilities. Use of simulation may benefit trainees in attaining a level of
      technical expertise that will benefit themselves and their patients. Furthermore,
      there is likely a need to establish a simulation-based certification process for
      graduating trainees to further ascertain minimum technical abilities.

PMID- 20674244
TI  - Microcirculatory effects of local and remote ischemic preconditioning in
      supraceliac aortic clamping.
AB  - INTRODUCTION: Supraceliac aortic clamping in major vascular procedures promotes
      splanchnic ischemia and reperfusion (I/R) injury that may induce endothelial
      dysfunction, widespread inflammation, multiorgan dysfunction, and death. We
      tested the hypothesis that local or remote ischemic preconditioning (IPC) may be
      protective against injury after supraceliac aortic clamping through the
      modulation of mesenteric leukocyte-endothelial interactions, as evaluated with
      intravital microscopy and expression of adhesion molecules. METHODS: Fifty-six
      male Wistar rats (weight, 190 to 250 g), were divided into four groups of 14 rats
      each: control-sham surgery without aortic occlusion; I/R through supraceliac
      aortic occlusion for 20 minutes, followed by 120 minutes of reperfusion; local
      IPC through supraceliac aortic occlusion for two cycles of 5 minutes of ischemia
      and 5 minutes of reperfusion, followed by the same protocol of the IR group;
      remote IPC through infrarenal aortic occlusion for two cycles of 10 minutes of
      ischemia and 10 minutes of reperfusion, followed by the same protocol of the IR
      group. Seven animals per group were used to evaluate in vivo leukocyte
      endothelial interactions in postcapillary venules with intravital microscopy and
      another seven animals per group were used to collect mesentery samples for
      immunohistochemistry demonstration of adhesion molecules expression. RESULTS:
      Supraceliac aortic occlusion increased the number of rolling leukocytes with
      slower velocities and increased the number of adherent leukocytes to the venular
      surface and leukocyte migration to the interstitium. The expression of P
      selectin, E-selectin, and intercellular adhesion molecule-1 was also increased
      significantly after I/R. Local or remote IPC reduced the leukocyte recruitment in
      vivo and normalized the expression of adhesion molecules. CONCLUSIONS: Local or
      remote IPC reduces endothelial dysfunction on mesenteric microcirculation caused
      by I/R injury after supraceliac aortic clamping.

PMID- 20674245
TI  - Midterm outcome of endovascular repair of ruptured isolated iliac artery
      aneurysms.
AB  - PURPOSE: This study analyzed the clinical and morphologic outcomes of
      endovascular treatment of ruptured isolated iliac artery aneurysms (RIIAA) at
      midterm follow-up. METHODS: Eleven patients with RIIAA (1 woman, 10 men; mean
      age, 73 years; mean IIAA diameter, 69.1 mm) were identified in a single-center
      database of patients who underwent endovascular aortoiliac aneurysm repair
      between April 2001 and December 2009. Devices inserted included 9 leg endografts
      in 7 patients (Excluder, n=7; Zenith, n=2), 3 bifurcated stent grafts in 3
      patients (Excluder), and 1 aortouniiliac stent graft in 1 patient (Zenith).
      Endovascular occlusion of the internal iliac artery or its branches was performed
      in all cases by coils (n=10) or Amplatzer occluder plug (n=1). Immediately after
      endovascular aneurysm exclusion, a computed tomography (CT) angiography was
      obtained in nine patients. Except for this adjunct postimplantation CT scanning,
      the imaging follow-up was the same as for nonruptured aortoiliac aneurysms at 3,
      6, and 12 months and annually thereafter. RESULTS: Mean delay from hospital
      admission to intervention was 78.5 minutes. Mean intervention time was 150
      minutes. The assisted primary technical success rate was 100%. Median lengths of
      stay were 2 days in the intensive care unit and 13 days in the hospital.
      Abdominal compartment syndrome developed in three patients who received open
      abdomen treatment. The 30-day mortality was 18%. The mean follow-up was 23 months
      (range, 0-69 months). There were no late deaths during the follow-up. There was
      no need for late surgical conversion. Aneurysm sac shrinkage (defined as >5 mm)
      was recorded in five patients, whereas the sac diameter remained stable in four.
      There was no patient with aneurysm sac growth. Additional stent graft insertion
      as the only secondary intervention for a type Ib leak was performed. Type II
      endoleaks (primary and secondary) were found in 36% and secondary Ib in 9% of the
      patients. CONCLUSION: Emergency stent grafting of RIIAA is feasible and safe with
      good midterm outcome.

PMID- 20674246
TI  - Usefulness and limitations of computational models in aortic disease risk
      stratification.
AB  - OBJECTIVE: In risk stratification of aortic diseases such as aneurysm and aortic
      dissection, diameter is one parameter whose influence on the average aortic wall
      stress is directly described by the Laplace law. More advanced mechanical models
      can be used and may yield additional information, such as transmural stress
      distributions. The question then arises of how refined models need to be to
      provide clinicians with practical help. METHODS: Two sets of finite element
      models were used. The relative roles of diameter, material stiffness,
      longitudinal stretch, blood pressure, wall thickness, and vessel curvature were
      explored using simplified aortic models for comparison with the Laplace law. The
      influences of the material properties nonlinearity and residual stress on the
      transmural stress distribution were investigated using an advanced aortic model
      including recent experimental findings in older humans. RESULTS: The Laplace law
      was confirmed as one effective, basic tool to assess the average wall stress in
      the aortic wall, both in the circumferential and longitudinal directions.
      However, the simplified models were sufficient to show that, as already reported
      in the literature, longitudinal stretch and vessel curvature have potentially
      equally strong or even stronger contributions to wall stress than the parameters
      included in the Laplace law. When the advanced model was used, and residual
      stress induced by large opening angles such as found in older subjects was
      introduced, the transmural stress gradient was found inverted compared with
      expectations, with the largest stresses now toward the adventitia. The results
      suggested that the intima may be increasingly shielded from higher stresses as
      one gets older, which might be protective against the initiation of dissection
      tears in the thoracic aorta. CONCLUSION: Biomechanical analysis of the aorta may
      be refined by using increasingly detailed computational models. Simplified models
      can readily improve on the Laplace law in the assessment of aortic wall stress,
      and as such, may already contribute to better risk stratification of aortic
      disease. Advanced models may also enhance our understanding of the mechanistic
      aspects in the pathogenesis of aortic disease. However, their applicability in a
      patient-specific context may be limited by the large number of input data they
      require, some of which might stay out of the clinicians' reach.

PMID- 20674247
TI  - Lessons learned from the analysis of gender effect on risk factors and procedural
      outcomes of lower extremity arterial disease.
AB  - INTRODUCTION: Despite overall improvement, there is still a gender-related
      disparity in the outcomes of lower extremities peripheral arterial disease (PAD).
      We analyzed sex-related variability among factors that are known to influence
      outcomes. METHODS: Data on PAD inpatient hospitalizations from New York, New
      Jersey, and Florida state hospital discharge databases (1998-2007) were analyzed
      using univariate and multivariate logistic regression analyses. RESULTS: Of the
      372,692 surgical hospitalizations identified, 162,730 (43.66%) involved women.
      Men and women undergoing vascular procedures differed in that more men smoked
      (18% vs 14%; P<.0001), and more men had coronary artery disease (40% vs 33%;
      P<.0001). Women were more likely to be obese (11.86% vs 4.89%; P<.0001), black
      (18.81% vs 12.66%; P<.0001), older, and have critical limb ischemia (CLI) (39.41%
      vs 37.67%; P<.0001). They had higher mortality (5.26% vs 4.21%; P<.0001) and
      complication rates, especially bleeding (10.62 % vs 8.19%; P<.0001) and infection
      (3.23% vs 2.88%; P<.0001). Mortality rates after endovascular procedures were
      lower and showed marginal difference between genders (2.87% vs 2.11%; P<.0001).
      The difference was more pronounced after open revascularizations (5.05% for women
      vs 4.00% for men; P<.0001) and amputations (9.82% for women vs 8.82% for men;
      P<.0001). Bleeding differences between men and women were greatest when both open
      and endovascular procedures were done during the same hospitalizations and lowest
      after major amputations. Similar to bleeding, transgender differences in
      postoperative infections were more pronounced after combination of open and
      endovascular procedures. Using a multivariable model, female gender remained a
      predictor of perioperative mortality, infection, and bleeding after vascular
      intervention (odds ratios 1.15, 1.21, and 1.32, respectively). Female gender
      negatively influenced the mortality of patients with cerebrovascular and coronary
      disease and those of black race even after adjusting for relevant clinical and
      demographic risk factors. Gender effect on mortality dissipated in octogenarians
      and patients with claudication. CONCLUSION: Female gender continues to be an
      important risk factor that negatively influences the outcomes of vascular
      interventions; however, these effects vary between different high-risk groups and
      procedures. Gender effect on mortality dissipates in elderly patients. Prompt
      recognition of the associations between gender and various risk factors of
      cardiovascular disease and aggressive modification of these risk factors in
      female patients may improve gender-related disparity in the outcomes of vascular
      disease.

PMID- 20674248
TI  - Prior endovascular abdominal aortic aneurysm repair provides no survival benefits
      when the aneurysm ruptures.
AB  - OBJECTIVE: It has been proposed that prior endovascular abdominal aortic aneurysm
      (AAA) repair (EVAR) confers protective effects in the setting of ruptured AAA
      (rAAA). This study was conducted to compare outcomes of rAAA repairs in patients
      with and without prior EVAR. METHODS: A retrospective review identified 18
      patients with (group 1) and 233 patients without (group 2) antecedent EVAR who
      presented with rAAA from January 2001 to December 2008. Patient characteristics
      and perioperative variables were noted and the outcomes were compared. Multiple
      logistic regression was used to identify factors contributing to morbidity and
      mortality and Kaplan-Meier analyses to estimate late survival rates. RESULTS:
      Baseline characteristics were similar between groups. Mean age was 78 years in
      group 1 and 74.8 years in group 2 (P=.17). Men comprised 83.3% of patients in
      group 1 and 77.3% in group 2 (P=.77). Hemodynamic instability at rAAA was noted
      with similar frequency between groups, 55.6% vs 52.6%, respectively (P=.99). Mean
      time from EVAR to rAAA was 4.0 years and from last follow-up computed tomography
      (CT) 1.2 years. The devices involved were Ancure (Guidant, Menlo Park, Calif)
      (9), AneuRx (Medtronic, Minneapolis, Minn) (5), Zenith (Cook Medical Inc,
      Bloomington, Ind) (3), and Excluder (W.L Gore, Flagstaff, Ariz) (1). Mean
      preoperative AAA size was 6.4 cm in group 1. All but 1 patient had an endoleak at
      the time of rupture. Of 14 patients with CT follow-up, only 3 patients had a
      known increase in size (>=5 mm) and only 3 were known to have an endoleak.
      Fifteen patients were treated by a single intervention, whereas 3 patients
      underwent multiple procedures. In group 2, open repair was performed in 218
      patients and EVAR in 15. Morbidity (66.7% vs 56.7%) and in-hospital mortality
      (38.9% vs 36.9%) were nearly identical between groups. One-year survival rates
      (27.8% vs 48.2%; P=.15) were also similar. The mortality rates for EVAR for
      primary rAAA was 20% as compared to 38.1% for open repair for rAAAs (P=.27).
      CONCLUSION: rAAA remains a lethal problem in patients with and without prior EVAR
      alike. An existing endograft provides neither acute nor 1-year survival benefits
      after rAAA repairs. Prediction of patients at risk for rupture post-EVAR is
      difficult, as only a minority of patients had a known prior endoleak or sac
      enlargement.

PMID- 20674249
TI  - Seventeen-year follow-up after ascending-to-infrarenal aorta bypass for recurrent
      coarctation in an adult.
AB  - Anatomic repair of complex aortic coarctation is associated with significant
      mortality and morbidity, including paraplegia. Extra-anatomic bypass strategies
      have been developed to reduce these complications and allow the correction of any
      concomitant conditions during the same operation. We present the case of a woman
      with uncontrolled hypertension and preductal coarctation of the aorta diagnosed
      at age 22 who underwent an unsuccessful attempt at primary repair, followed by
      extra-anatomic bypass from the ascending-to-infrarenal aorta. The patient has
      remained normotensive, with no additional complications related to the disease or
      the procedure, during a follow-up of 17 years.

PMID- 20674251
TI  - A vascular disease educational program in the preclinical years of medical school
      increases student interest in vascular disease.
AB  - BACKGROUND: New training paradigms in vascular surgery necessitate medical
      student interest in vascular disease. We examined the effects of incorporation of
      a vascular disease educational program during the second year of the medical
      school curriculum on student acquisition of knowledge and interest in the
      treatment of vascular disease. METHODS: We developed and administered a new
      educational program on vascular disease and delivered the program to all second
      year medical students. The new program encompassed 9 didactic hours, including 7
      traditional lecture hours and 2 hours of problem-based learning. After completing
      the program, students were surveyed regarding vascular disease-specific
      knowledge, interest in treating vascular disease, and career choices. Third-year
      students who were not exposed to the program were surveyed as a control group. We
      recorded the voluntary student enrollment in the vascular and endovascular
      surgery rotation during the following academic year. Voluntary enrollment of the
      students exposed to the vascular disease education program was compared with
      enrollment for the previous 8 years. RESULTS: Before the introduction of the new
      educational program, 946 total lecture hours were delivered to first- and second
      year medical students, comprising 490 hours (52%) given by nonsurgeon physicians,
      445 (47%) by nonphysicians, and 11 (1%) by surgeons. Survey response rate was 93%
      (112 of 121) for second-year students and 95% (39 of 41) for third-year students.
      After the vascular disease program, second-year students answered 7.1 +/- 1.4 of
      9 vascular disease questions correctly, whereas unexposed third-year students
      answered 7.2 +/- 1.7 questions correctly (P = .96). Most second-year medical
      students described a "somewhat" or "much greater" interest in the medical (63%),
      procedural (59%), and overall (63%) management of vascular disease after exposure
      to the program. Most also had a "somewhat" or "much greater" interest in a
      vascular medicine (64%) or vascular and endovascular surgery (60%) rotation.
      Enrollment in the vascular surgery third-year clerkship increased significantly
      to a mean of 3.0 students/month from 1.16 students/month in the prior year (P =
      .0032, postintervention year vs 8 prior years). CONCLUSION: A vascular disease
      educational program administered to second-year medical students increases
      interest in vascular disease and interest in further training. The increased
      interest translates to greater student enrollment in the vascular surgery
      clerkship in the subsequent academic year.

PMID- 20674252
TI  - The structure and processes of the Pacific Vascular Symposium 6.

PMID- 20674253
TI  - Two-stage operative cytoreduction and intraperitoneal chemotherapy for diffuse
      malignant peritoneal mesothelioma: Operative morbidity and mortality in phase I
      and II trials.
AB  - AIMS: The standard of care for diffuse malignant peritoneal mesothelioma involves
      operative cytoreduction and intraperitoneal chemotherapy. Most centers favor
      aggressive operative cytoreduction, accepting high morbidity and mortality. In
      our trials, patients underwent less extensive cytoreduction followed by prolonged
      intraperitoneal chemotherapy. Patients underwent a second cytoreduction with
      heated intraperitoneal chemotherapy. We hypothesized this would result in lower
      operative morbidity and mortality with similar survival. METHODS: Hospital
      records, discharge summaries, microbiology, radiography, and office records were
      retrospectively reviewed to supplement a prospective database. 30-day morbidity
      and mortality were categorized, and classified according to the Clavien
      methodology. RESULTS: 47 first and 39 second operations were performed with 13%
      and 26% morbidity, respectively. Mortality was 2%. Infections comprised 59% of
      the morbidity. Inclusive of both operations, formal peritonectomy was performed
      in 16% of patients, resection of isolated lesions in less than half, and only 19%
      had a visceral organs other than the spleen resected. At the completion of the
      protocol, only 3% of patients had visible intraperitoneal disease. The mean total
      length of stay for both operations combined was 16 +/- 23 days. Overall median
      survival was 54.9 months, and median survival for the epithelioid subtype was
      70.2 months. CONCLUSIONS: A two-stage cytoreduction with intraperitoneal
      chemotherapy offers median survival comparable to one-stage protocols, with
      relatively low morbidity, mortality, visceral resections and length of stay
      despite two operations. This series supports that our protocol is a feasible and
      safe approach.

PMID- 20674254
TI  - [Respiratory support using veno-venous ECMO during lung resection for
      aspergilloma].
AB  - Respiratory support using extra corporeal membrane oxygenation (ECMO) is rarely
      used in the setting of adult lung surgery, with the exception of lung
      transplantation. We report the case of a patient with pulmonary aspergilloma, for
      whom selective bronchial intubation was required to facilitate surgery.
      Intolerance to unilateral ventilation was anticipated due to poor underlying lung
      function. Intra-operatively, an attempt to lung exclusion was responsible for
      severe hypoxemia. The use of veno-venous ECMO allowed to improve oxygenation and
      lung resection was carried out successfully at the expense of major intra
      operative bleeding.

PMID- 20674255
TI  - [Letter on the article: "What philosophy can say about immunogenicity"].

PMID- 20674258
TI  - [Nonsurgical management of obesity in adults].
AB  - General practitioners are placed in an ideal position to manage obesity. First,
      they have to consider the motivation of the obese patient to change his habits.
      When the patient is not motivated to loss weight, their role is to identify and
      treat co-morbidities, to evaluate the risk related to the obesity and to
      establish a therapeutic diagnosis to evaluate motivation and ability to change.
      If the patient is motivated, the therapeutic choices have to be adapted
      individually to each patient. An inadequate management may not only result in a
      failure but may increase obesity. The objectives in obesity treatment are to
      achieve weight loss in order to reduce health risk as far as possible, to
      maintain that weight loss, to restore quality of life. Goals and methods must be
      realistic. Even a modest weight loss (5-10 % of initial weight) will improve
      health indices in an obese patient. Dietary treatment and physical activity are
      fundamental to the management of obesity. Compliance with the diet is the major
      problem, especially during the phase of weight maintenance after the excess
      weight loss has been lost. Initial weight reduction depends on the level of
      energy deficit and weight maintenance on compliance to a low fat diet and a
      physical activity programme. Cognitive behavioural approaches should be an
      integral part of the management of a chronic disease. This treatment is very
      useful to improve body image, self-esteem, management of stress and control of
      disordered eating patterns. A psychotherapeutic approach is often necessary,
      especially when the obesity is psycho-determined. Obesity drugs should be used
      for carefully selected patients, as an adjunct to diet therapy and lifestyle
      modifications, under medical supervision.

PMID- 20674256
TI  - [Epidermolysis bullosa acquisita].
AB  - Epidermolysis bullosa acquisita (EBA) is a rare autoimmune subepidermal bullous
      disease with autoimmunity to the type VII collagen which is the major component
      of anchoring fibrils. Clinical manifestations of the classical EBA include skin
      fragility, blisters over the trauma-prone surfaces and milium cysts. Other
      presentations of EBA have been reported: mucosal predominant appearance
      reminiscent of cicatricial pemphigoid, bullous pemphigoid-like presentation and
      IgA-EBA. Making a definitive diagnosis of EBA could be difficult because
      specialized tests available in only some laboratories are necessary to confirm
      the clinical suspicion: immunoelectron microscopy demonstrating immune deposits
      on anchoring fibrils and immunoblotting or enzyme-linked immunosorbent assay
      (Elisa) detecting autoantibodies recognizing the type VII collagen. EBA
      frequently is associated with Crohn's disease and an inflammatory bowel disease
      must be ruled out in patients with EBA and abdominal manifestations. EBA
      potentially is serious, has usually a chronical evolution and is difficult to
      treat.There are no guidelines for treatment of EBA, which is adapted to clinical
      severity and include dapsone, cyclosporine and rituximab.

PMID- 20674259
TI  - Nepafenac-assisted mydriasis in a rabbit model.
AB  - PURPOSE: To compare the effectiveness of nepafenac 0.10% in achieving and
      maintaining pupil dilation with the effectiveness of flurbiprofen 0.03% and a
      placebo in a rabbit model. SETTING: Department of Ophthalmology, University of
      California, San Francisco, California, USA. DESIGN: Laboratory study. METHODS:
      Adult pigmented rabbits were randomized to 3 equal-sized groups: placebo,
      flurbiprofen, and nepafenac. Cataract surgery was performed in randomized order
      by a surgeon who was masked to group assignment. The treatment or placebo was
      administered starting 1 day before surgery. Phenylephrine 10.0% was administered
      starting 30 minutes before surgery. Phacoemulsification was performed in standard
      fashion. Pupil measurements were recorded before and after surgery. A linear
      mixed model with a random effect for the rabbits and a fixed effect for the
      treatment groups was used to compare mean pupil diameters between groups.
      RESULTS: Baseline pupil measurements were similar between the placebo,
      flurbiprofen, and nepafenac groups. Preoperative pupil dilation was statistically
      significantly greater in the nepafenac group (mean 11.5 mm +/- 0.5 [SD]) than in
      the placebo group (mean 10.2 +/- 1.1 mm) and the flurbiprofen group (mean 9.9 +/-
      1.1 mm) (P<.005 and P<.001, respectively). The greater dilation was maintained at
      the end of surgery, at which time the nepafenac group had statistically
      significantly larger pupils (mean 9.4 +/- 1.2 mm) than the placebo group (mean
      7.9 +/- 0.6 mm) and the flurbiprofen group (mean 8.5 +/- 0.9 mm) (P<.001 and
      P<.05, respectively). CONCLUSION: Nepafenac was more effective than a placebo and
      flurbiprofen in achieving maximum preoperative and postoperative pupil mydriasis
      in rabbits.

PMID- 20674260
TI  - Standing phacoemulsification: a prospective audit of 20 consecutive cases.
AB  - PURPOSE: To audit the surgical and postoperative complications and the visual
      outcomes of standing phacoemulsification and compare these with the results of
      conventional seated phacoemulsification. SETTING: District general hospital,
      Sidcup, England. DESIGN: Prospective comparative case series. METHODS: This
      prospective audit comprised consecutive patients having standing
      phacoemulsification; a control group was drawn from all conventional
      phacoemulsification procedures on the same operating lists. One eye per patient
      was included. Demographic and surgical data, complications, and preoperative and
      postoperative visual acuity and intraocular pressure were recorded. Paired and
      unpaired t tests were used to compare mean values, and the chi-square test with
      Yates correction or the Fisher exact test was used to compare frequencies.
      RESULTS: Twenty patients requiring standing phacoemulsification and 89 control
      patients were enrolled over a 32-month period. The 2 groups were similar in
      characteristics except the standing group was younger (68.2 years versus 78.0
      years) (P<.005) and had a longer axial length (23.8 mm versus 23.1 mm) (P<.05).
      No patient in the standing group and 6% of patients in the control group had
      operative complications, although the difference between groups was not
      statistically significant. The rates of postoperative complications were
      comparable. Pinhole-corrected distance visual acuity was similar (6/12 or better:
      90% in standing group and 94% in control group; 6/6 or better: 55% and 44%,
      respectively). Best-case analyses were similar between groups (6/12 or better,
      100% versus 98%; 6/6 or better, 58% versus 51%). CONCLUSIONS: Standing
      phacoemulsification was as safe as conventional seated surgery when performed by
      the same experienced surgeon. Visual results were excellent.

PMID- 20674261
TI  - Optimizing the vault of collagen copolymer phakic intraocular lenses in eyes with
      keratoconus and myopia: comparison of 2 methods.
AB  - PURPOSE: To compare 2 methods for optimizing the final central vault of a
      collagen copolymer posterior chamber phakic intraocular lens (pIOL) (Visian
      Implantable Collamer Lens) in eyes with keratoconus and myopia. SETTING: Private
      practice, Beverly Hills, California, USA. DESIGN: Comparative interventional
      study. METHODS: The length of the pIOL to implant in keratoconic eyes with myopia
      was selected based on the white-to-white (WTW) distance or the sulcus-to-sulcus
      (STS) distance using the pIOL manufacturer's protocol. The final central vault
      distance was compared a minimum of 3 months postoperatively. RESULTS: The pIOL
      length was based on WTW measurements in 8 eyes of 6 patients and on STS
      measurements in 8 eyes of 5 patients. There was no significant difference between
      the 2 groups in the mean preoperative WTW distance, STS distance, or manifest
      refraction spherical equivalent (MRSE) (P = .22, P = .37, and P = 1.00,
      respectively). The mean postoperative vault was 1.03 corneal thickness +/- 0.72
      (SD) in the WTW group and 1.18 +/- 0.35 corneal thickness in the STS group (P =
      .61). The vault distance was less than 1.0 corneal thickness in 3 eyes (37.5%) in
      the WTW group and 1 eye (12.5%) in the STS group. A small postoperative vault was
      associated with a high preoperative MRSE (P = .03). CONCLUSIONS: The WTW and STS
      methods both provided adequate final central pIOL vault in keratoconic eyes with
      myopia. The STS calculations gave greater final vault and higher vault
      predictability, although the difference between the 2 methods was not
      statistically significant.

PMID- 20674262
TI  - Correlation between keratometric and refractive astigmatism in pseudophakic eyes.
AB  - PURPOSE: To determine the correlation between refractive and keratometric
      astigmatism in pseudophakic eyes. SETTING: Vissum Madrid, Madrid, Spain. DESIGN:
      Case series. METHODS: Consecutive eyes that had phacoemulsification with
      intraocular lens implantation during the first quarter of 2003 were evaluated.
      The refractive and keratometric astigmatism were compared 2 months
      postoperatively. RESULTS: The mean postoperative keratometric astigmatism (0.91
      diopter [D] +/- 0.67 [SD]) in the 121 eyes was statistically significantly higher
      than the mean postoperative refractive astigmatism (0.64 +/- 0.72 D) (P<.0001).
      Regression analysis found a significant correlation between the refractive and
      keratometric errors of the J0 component (P<.001, r(2) = 0.29) and between the
      refractive and keratometric errors of the J45 component (P<.001, r(2) = 0.36)
      CONCLUSION: Keratometric astigmatism was responsible for about 30% of the
      refractive astigmatism in pseudophakic eyes. Other undetermined factors induce
      astigmatism in these cases.

PMID- 20674263
TI  - Electrophysiological correlates of semantic processing in Williams syndrome.
AB  - Williams syndrome (WS), a genetic neurodevelopmental disorder due to
      microdeletion in chromosome 7, has been described as a syndrome with an
      intriguing socio-cognitive phenotype. Cognitively, the relative preservation of
      language and face processing abilities coexists with severe deficits in visual
      spatial tasks, as well as in tasks involving abstract reasoning. However, in
      spite of early claims of the independence of language from general cognition in
      WS, a detailed investigation of language subcomponents has demonstrated several
      abnormalities in lexical-semantic processing. Nonetheless, the neurobiological
      processes underlying language processing in Williams syndrome remain to be
      clarified. The aim of this study was to examine the electrophysiological
      correlates of semantic processing in WS, taking typical development as a
      reference. A group of 12 individuals diagnosed with Williams syndrome, with age
      range between 9 and 31 years, was compared with a group of typically developing
      participants, individually matched in chronological age, gender and handedness.
      Participants were presented with sentences that ended with words incongruent
      (50%) with the previous sentence context or with words judged to be its best
      completion (50%), and they were asked to decide if the sentence made sense or
      not. Results in WS suggest atypical sensory ERP components (N100 and P200),
      preserved N400 amplitude, and abnormal P600 in WS, with the latter being related
      to late integration and re-analysis processes. These results may represent a
      physiological signature of underlying impaired on-line language processing in
      this disorder.

PMID- 20674264
TI  - The relationship between motor abilities and early social development in a
      preschool cohort of children with cerebral palsy.
AB  - AIM: To investigate the relationship between motor ability and early social
      development in a cohort of preschool children with cerebral palsy (CP). DESIGN:
      Population-based cohort study. METHODS: Participants were 122 children with CP
      assessed at 18, 24 and 30 months, corrected age (ca). Motor ability was measured
      by the Gross Motor Function Classification System (GMFCS) with classification
      assigned by physiotherapists. The sample was representative of a population-based
      cohort (I=48, 38.4%, II=19, 15.2%, III=17, 13.6%, IV=22, 17.6% and V=19, 15.2%).
      Social development was measured by the Paediatric Evaluation of Disability
      Inventory (PEDI) and included capabilities in social interaction, social
      communication, interactive play and household/community tasks. RESULTS: Cross
      sectional analyses indicated a significant relationship between motor ability and
      social development at 18 months, F(4, 56)=11.44, p<.0001, eta(2)=.45, at 24
      months, F(4, 79)=15.66, p<.0001, eta(2)=.44 and at 30 months, F(4, 76)=16.06,
      p<.0001, eta(2)=.49. A longitudinal analysis with a subset of children (N=24)
      indicated a significant interaction between age at assessment and GMFCS, F(2,
      21)=7.02, p=.005, eta(2)=.40. Comparison with community norms indicated that at
      18 months corrected age, 44.3% of the cohort was greater than two standard
      deviations below the mean (>2SD) for social development and a further 27.9% of
      the cohort was greater than one standard deviation below the mean (>1SD).
      INTERPRETATION: There is a relationship between motor ability and social
      development in preschool children with CP. Children with CP may require support
      for social development in additional to physical interventions, from as early as
      18 months.

PMID- 20674265
TI  - Gait patterns in hemiplegic children with Cerebral Palsy: comparison of right and
      left hemiplegia.
AB  - The aims of this study are to compare quantitatively the gait strategy of the
      right and left hemiplegic children with Cerebral Palsy (CP) using gait analysis.
      The gait strategy of 28 right hemiparetic CP (RHG) and 23 left hemiparetic CP
      (LHG) was compared using gait analysis (spatio-temporal and kinematic parameters)
      and considering the hemiplegic classification based on four gait strategies. Our
      results demonstrated that velocity was a significant parameter to differentiate
      RHG and LHG: all hemiplegic types revealed in fact that RHG walked with higher
      velocity than LHG. The ankle strategy displayed an increased number of
      differences between RHG and LHG from hemiplegia of Type I to Type III. In all the
      comparison, the LHG showed the less physiological gait pattern. As for knee
      kinematics, differences between right and left hemiplegic gait pattern were
      evidenced only in children with hemiplegia Type II: the LHG walked with a more
      flexed knee at initial contact, marked hyperextension in midstance and reduced
      knee flexion ability in the swing phase. The hip strategy was quite normal in
      both groups in hemiplegia Type I. In the other two types, LHG showed a limited
      extension ability in midstance in comparison to RHG. In conclusion, our data
      revealed that RHG and LHG were in general characterised by different gait
      patterns, evidencing a general a progression of involvement in the different
      types of hemiplegia; in particular in all the hemiplegic types the LHG patients
      revealed a more severe involvement than the RHG individuals and the differences
      were more evident at the distal joints, especially at the ankle joint.

PMID- 20674266
TI  - Aerobic capacity in children and adolescents with cerebral palsy.
AB  - This study described the aerobic capacity [VO(2peak) (ml/kg/min)] in contemporary
      children and adolescents with cerebral palsy (CP) using a maximal exercise test
      protocol. Twenty-four children and adolescents with CP classified at Gross Motor
      Functional Classification Scale (GMFCS) level I or level II and 336 typically
      developing children were included. All children performed a progressive exercise
      test on a treadmill with respiratory gas-exchange analysis. The results are
      compared with normative values for age and gender-matched controls. Aerobic
      capacity of children and adolescents with CP, who are classified at GMFCS level I
      or II was significantly lower than that of typically developing controls.
      Especially in girls with CP, the aerobic capacity deteriorated with age. The
      aerobic capacity of contemporary children and adolescents with CP, who are
      classified at GMFCS level I or II is significantly lower than that of typically
      developing controls.

PMID- 20674267
TI  - Improving social understanding of individuals of intellectual and developmental
      disabilities through a 3D-facail expression intervention program.
AB  - Individuals with intellectual and developmental disabilities (IDD) have specific
      difficulties in cognitive social-emotional capability, which affect numerous
      aspects of social competence. This study evaluated the learning effects of using
      3D-emotion system intervention program for individuals with IDD in learning
      socially based-emotions capability in social contexts. The 3D-emotion system
      involves three stages with 24 questions with designed different social events.
      The experimental study was to evaluate using a single subject design on three
      participants with IDD for identifying the effects of 3D-emotion system
      intervention program; and the collected data of using this system and informal
      interview with the participants' were involved. The results showed that three
      participants had significant positive effects on using of the 3D-emotion system
      intervention program, and in terms of follow-up learning have been discussed in
      this paper.

PMID- 20674268
TI  - Probabilistic self-organizing maps for qualitative data.
AB  - We present a self-organizing map model to study qualitative data (also called
      categorical data). It is based on a probabilistic framework which does not assume
      any prespecified distribution of the input data. Stochastic approximation theory
      is used to develop a learning rule that builds an approximation of a discrete
      distribution on each unit. This way, the internal structure of the input dataset
      and the correlations between components are revealed without the need of a
      distance measure among the input values. Experimental results show the
      capabilities of the model in visualization and unsupervised learning tasks.

PMID- 20674269
TI  - Modeling cognitive and emotional processes: a novel neural network architecture.
AB  - In our continuous attempts to model natural intelligence and emotions in machine
      learning, many research works emerge with different methods that are often driven
      by engineering concerns and have the common goal of modeling human perception in
      machines. This paper aims to go further in that direction by investigating the
      integration of emotion at the structural level of cognitive systems using the
      novel emotional DuoNeural Network (DuoNN). This network has hidden layer
      DuoNeurons, where each has two embedded neurons: a dorsal neuron and a ventral
      neuron for cognitive and emotional data processing, respectively. When input
      visual stimuli are presented to the DuoNN, the dorsal cognitive neurons process
      local features while the ventral emotional neurons process the entire pattern. We
      present the computational model and the learning algorithm of the DuoNN, the
      input information-cognitive and emotional-parallel streaming method, and a
      comparison between the DuoNN and a recently developed emotional neural network.
      Experimental results show that the DuoNN architecture, configuration, and the
      additional emotional information processing, yield higher recognition rates and
      faster learning and decision making.

PMID- 20674270
TI  - Aortic wall erosion after percutaneous closure of atrial septal defect.
AB  - A 26-year-old woman presented with acute hemolysis 1 month after percutaneous
      closure of an atrial septal defect. Three-dimensional transesophageal
      echocardiography was used to establish the diagnosis of a fistula from the aorta,
      toward the device and both atria. The patient required urgent surgical
      correction. Transcatheter closure of atrial septal defects has proven to be a
      highly successful alternative to surgery in the appropriate patient. Cardiac
      perforation and device erosion of the aortic wall are infrequent but potentially
      lethal complications of percutaneous occluder device insertion. Supportive
      features of device erosion include a wrong preimplantation assessment of the
      rims, the device extends across the atrial septum, and the device encroaches on
      the surrounding structures. In this case, the presumed mechanism of aortic
      fistula was aortic erosion by the left atrial disk of the occluder device.

PMID- 20674271
TI  - Activation of the type I interferon pathway in primary Sjogren's syndrome.
AB  - Sjogren's syndrome (SS), a chronic autoimmune systemic disease affecting middle
      aged women, is characterized by lymphocytic infiltration of the salivary and
      lachrymal glands resulting in dry eyes and dry mouth. Recent advances have
      revealed a major role for activation of the type I interferon (IFN) pathway in
      the pathogenesis of the syndrome, as evidenced by the increased circulating type
      I IFN activity and an IFN "signature" in peripheral blood mononuclear cells
      (PBMC) and minor salivary gland (MSG) biopsies from these patients. Polymorphisms
      in genes involved in the IFNalpha pathway, such as IRF5 and STAT4, have been
      found to be associated with disease susceptibility. While the initial triggers of
      the innate immune response in SS remain elusive, preliminary evidence supports
      the role of inappropriately expressed endogenous LINE-1 (L1) retroelements as
      potential triggers of type I IFN activation in SS, possibly through Toll-like
      receptor (TLR) dependent or independent pathways. Proteins of the methylation
      machinery and the APOBEC family of cytidine deaminases are coordinately
      overexpressed, suggesting that those proteins might contribute to regulation of
      the inappropriately expressed L1 endogenous retroelements in SS. Given the
      apparent central role of IFNalpha in the pathogenesis of SS, blockade of this
      cytokine may be a rational therapeutic approach. In the current review we
      summarize the current evidence regarding the potential triggers of type I IFN
      activation as well as the data supporting genetic and epigenetic regulation of
      the type I IFN system in SS.

PMID- 20674272
TI  - Intralesional injection of triamcinolone hexacetonide as an alternative treatment
      for central giant-cell granuloma in 21 cases.
AB  - Central giant-cell granulomas are benign, but occasionally aggressive, lesions
      that traditionally have been treated surgically. 21 cases of central giant-cell
      granuloma of the jaw were treated with intralesional injection of
      corticosteroids. The treatment protocol adopted was intralesional injection of
      20mg/ml triamcinolone hexacetonide diluted in an anaesthetic solution of 2%
      lidocaine/epinephrine 1:200,000 in the proportion 1:1; 1.0ml of the solution was
      infiltrated for every 1cm(3) of radiolucid area of the lesion, totalling 6
      biweekly applications. Ten patients had aggressive lesions and 11 nonaggressive.
      Two patients showed a negative response to the treatment and underwent surgical
      resection, 4 showed a moderate response and 15 a good response. 8 of the 19 who
      had a moderate-to-good response to the drug treatment underwent osteoplasty to
      reestablish facial aesthetics. In these cases, only mature or dysplastic bone was
      observed, with the presence or absence of rare giant multinucleated cells. The
      advantages of this therapy are its less-invasive nature, the probable lower cost
      to the patient, lower risk and the ability to treat the lesion surgically in the
      future, if necessary.

PMID- 20674273
TI  - Quantitative EEG abnormalities in persons with "pure" epileptic predisposition
      without epilepsy: a low resolution electromagnetic tomography (LORETA) study.
AB  - OBJECTIVE: Epileptic predisposition means genetically determined, increased
      seizure susceptibility. Neurophysiological evaluation of this condition is still
      lacking. In order to investigate "pure epileptic predisposition" (without
      epilepsy) in this pilot study the authors prospectively recruited ten persons who
      displayed generalized tonic-clonic seizures precipitated by 24 or more hours of
      sleep deprivation but were healthy in any other respects. METHODS: 21-channel
      EEGs were recorded in the morning, in the waking state, after a night of
      sufficient sleep in the interictal period. For each person, a total of 120s
      artifact-free EEG was processed to low resolution electromagnetic tomography
      (LORETA) analysis. LORETA activity (Ampers/meters squared) was computed for 2394
      voxels, 19 active electrodes and 1Hz very narrow bands from 1 to 25Hz. The data
      were compressed into four frequency bands (delta: 0.5-4.0Hz, theta: 4.5-8.0Hz,
      alpha: 8.5-12.0Hz, beta: 12.5-25.0Hz) and projected onto the MRI figures of a
      digitized standard brain atlas. The band-related LORETA results were compared to
      those of ten, age- and sex-matched healthy persons using independent t-tests.
      p<0.01 differences were accepted as statistically significant. RESULTS:
      Statistically significant decrease of alpha activity was found in widespread,
      medial and lateral parts of the cortex above the level of the basal ganglia.
      Maximum alpha decrease and statistically significant beta decrease were found in
      the left precuneus. Statistically not significant differences were delta increase
      in the medial-basal frontal area and theta increase in the same area and in the
      basal temporal area. DISCUSSION: The significance of alpha decrease in the
      patient group remains enigmatic. beta decrease presumably reflects non-specific
      dysfunction of the cortex. Prefrontal delta and theta increase might have
      biological meaning despite the lack of statistical significance: these findings
      are topographically similar to those reported in idiopathic generalized epilepsy
      in previous investigations. SIGNIFICANCE: Quantitative EEG characteristics of the
      genetically determined epilepsy predisposition were given in terms of frequency
      bands and anatomical distribution.

PMID- 20674274
TI  - Imaging foci of epileptic discharges from simultaneous EEG and fMRI using the
      canonical HRF.
AB  - PURPOSE: Simultaneous electroencephalography and functional magnetic resonance
      imaging (EEG-fMRI) is considered as a powerful and non-invasive method that
      allows definition of the irritative zone. However, the complex interictal
      epileptic discharge (IED) may be present in some patients, and sometimes no
      active foci can be localized using General Linear Model (GLM) which is a widely
      adopted tool in EEG-fMRI study. The purpose of this study is to develop a new
      scheme to improve the detectability and localize the canonical HRF localizable
      foci. METHOD: Various IEDs are classified using a combination of an independent
      component analysis (ICA) and a temporal correlation analysis between the
      independent components and the raw EEG channel; and the classified IEDs are then
      separately used for foci localization. This scheme is tested by ten patients with
      variable IEDs, including two patients whose activity could not be identified by
      common method. RESULT: Applying this scheme to the two patients, some foci
      consistent with electroclinical data were localized. When it was applied to the
      remaining eight patients with positive results using common method, 2-4 types of
      IEDs were classified, and the activity could be identified from at least one type
      of IED. The results were similar to that received from common method. CONCLUSION:
      These results indicate that the proposed scheme could enhance the imaging of the
      localizable foci by isolating its IEDs. This scheme is potentially a useful tool
      for epilepsy clinic.

PMID- 20674275
TI  - Bromoderma in a patient with migrating partial seizures in infancy.
AB  - A 5-month-old boy with migrating partial seizures in infancy acquired bromoderma
      4 weeks after initiating potassium bromide (KBr) therapy (60mg/kg/day).
      Erythematous pustules appeared on the forehead within a few days of attaching
      electroencephalography electrodes, and on the cheek at the site of nasogastric
      tube fixation. These later developed into vegetant plaques. Bromoderma aggravated
      at the site of skin biopsy that was performed 4 weeks after KBr termination.
      Bromoderma tuberosum should be recognized widely, considering the increasing use
      of KBr for treating intractable childhood epilepsy.

PMID- 20674276
TI  - Triple pathology in epilepsy: coexistence of cavernous angiomas and cortical
      dysplasias with other lesions.
AB  - Coexistence of cortical dysplasias (CD) with cavernomas has rarely been reported.
      We reviewed our surgical specimens from patients who underwent surgery for
      pharmacoresistant epilepsy between 2003 and 2008, and identified seven cases with
      cavernoma, of whom two had overlying CD. In addition, each of these patients had
      a third form of a potentially epileptogenic lesion: hippocampal sclerosis in one,
      and venous angioma in the other. We conclude that CD is heterogeneous, with
      milder forms appearing to co-exist with other pathologies, including vascular
      abnormalities and hippocampal sclerosis.

PMID- 20674277
TI  - RCTs with new antiepileptic drugs in children: a systematic review of monotherapy
      studies and their methodology.
AB  - Few randomised controlled trials (RCTs) have been performed in which a second
      generation antiepileptic drug (AED) used as monotherapy was compared with placebo
      or another AED in children (<18 years of age) with epilepsy. We describe the
      results of the available studies, assess the validity of these results, and give
      recommendations for optimal study design for AED monotherapy studies in children
      with epilepsy. Studies were identified using PubMed (Medline), Embase and the
      Cochrane Library (January 1990-January 2010). All reports were assessed for
      methodological quality and results were summarised descriptively. Nine RCTs were
      included. No difference in efficacy and safety between second-generation AEDs and
      first-generation AEDs in children was detected. Considerable heterogeneity in
      study design, inclusion criteria and primary endpoints impaired formal meta
      analysis and correct interpretation of results. Follow-up periods were between 2
      and 104 weeks; the dosage of the tested AEDs varied between studies, with
      sometimes use of apparent subtherapeutic dosages; in only two studies the method
      of randomisation was well described, in only three the power calculations;
      several studies did not use an intention-to-treat analysis. Although from the
      available studies first- and second-generation AEDs appear to have similar
      efficacy and safety in children with epilepsy, these trials are inadequate to
      provide a sufficient evidence base for decision making. Better trials are needed:
      AEDs should be studied in optimal paediatric doses, power should be sufficient to
      detect small but clinically relevant differences, and the follow-up period should
      be long enough. Most important, primary endpoint to be evaluated should be time
      to treatment failure or retention rate, since these outcomes combine efficacy and
      safety.

PMID- 20674278
TI  - Deficits in visual sustained attention differentiate genetic liability and
      disease expression for schizophrenia from Bipolar Disorder.
AB  - BACKGROUND: There is mounting evidence for shared genetic liability to psychoses,
      particularly with respect to Schizophrenia (SZ) and Bipolar Disorder (BD), which
      may also involve aspects of cognitive dysfunction. Impaired sustained attention
      is considered a cardinal feature of psychoses but its association with genetic
      liability and disease expression in BD remains to be clarified. METHODS: Visual
      sustained attention was assessed using the Degraded Symbol Continuous Performance
      Test (DS-CPT) in a sample of 397 individuals consisting of 50 remitted SZ
      patients, 119 of their first degree relatives, 47 euthymic BD patients, 88 of
      their first degree relatives and 93 healthy controls. Relatives with a personal
      history of schizophrenia or bipolar spectrum disorders were excluded. Performance
      on the DS-CPT was evaluated based on the response criterion (the amount of
      perceptual evidence required to designate a stimulus as a target) and sensitivity
      (a signal-detection theory measure of signal/noise discrimination). RESULTS: We
      found no effect of genetic risk or diagnosis for either disorder on response
      criterion. In contrast, impaired sensitivity was seen in SZ patients and to a
      lesser degree in their relatives but not in BD patients and their relatives.
      These findings were not attributable to IQ, medication, age of onset or duration
      of illness. CONCLUSIONS: Our results argue for the specificity of visual
      sustained attention impairment in differentiating SZ from BD. They also suggest
      that compromised visual information processing is a significant contributor to
      these deficits in SZ.

PMID- 20674280
TI  - Effects of cannabis use on age at onset in schizophrenia and bipolar disorder.
AB  - BACKGROUND: Cannabis use may decrease age at onset in both schizophrenia and
      bipolar disorder, given the evidence for substantial phenotypic and genetic
      overlap between both disorders. METHODS: 766 patients, aged 16 to 65 years, were
      assessed with the Composite International Diagnostic Interview (CIDI) for
      substance abuse/use. 676 subjects were diagnosed with schizophrenia and 90
      subjects with bipolar disorder. The influence of cannabis use on age at onset in
      both schizophrenia and bipolar disorder was examined using regression analysis.
      RESULTS: Cannabis and other substance use was more frequent in patients with
      schizophrenia compared to the bipolar group. Both cannabis use and a
      schizophrenia diagnosis predicted earlier age at onset. There was a significant
      interaction between cannabis use and diagnosis, cannabis having a greater effect
      in bipolar patients. Age at onset in users of cannabis was comparable in both
      diagnostic groups whereas bipolar non-users were significantly older than
      schizophrenia non-users at onset. CONCLUSION: Cannabis use may decrease age at
      onset in both schizophrenia and bipolar patients and reduce the effect of
      diagnosis. This is consistent with the view that cannabis use may unmask a pre
      existing genetic liability that is partly shared between patients with
      schizophrenia and bipolar disorder.

PMID- 20674279
TI  - Temporal processing in schizophrenia: effects of task-difficulty on behavioral
      discrimination and neuronal responses.
AB  - Deficits in temporal judgment in schizophrenia have been observed in behavioral
      and electrophysiological studies for years. The functional neuroanatomy of
      temporal judgment in schizophrenia is, however, poorly understood. Recent
      neurophysiological research suggests that timing deficits in this population may
      not be widespread across all timing tasks, but specifically associated with high
      levels of difficulty. We evaluated differences between individuals with
      schizophrenia (N=16) and healthy subjects (N=18) during a temporal discrimination
      task at two levels of difficulty. Subjects were studied with functional magnetic
      resonance imaging (fMRI) at 3T while discriminating tone durations. Behaviorally,
      the schizophrenia group performed worse than the control group at both levels of
      difficulty. Similarly, group differences in patterns of brain activation were
      observed across both difficulty conditions. In the easy condition, individuals
      with schizophrenia showed less activation in the supplementary motor area and
      insula/opercula, regions known to be involved in temporal processing. These group
      differences increased in the difficult condition. In addition, the striatum was
      less active in individuals with schizophrenia in the difficult condition.
      Comparing the difficult to easy conditions revealed robust differences in the
      bilateral striatum and the insula/opercula, suggesting that the striatum plays a
      key role in temporal processing deficits in schizophrenia, especially under
      difficult conditions. These observations suggest that temporal judgment deficits
      reflect widespread neuroanatomical network involvement in schizophrenia, some of
      which are not directly related to task difficulty. These findings shed light on
      disparate findings in the timing literature regarding the role of task difficulty
      in temporal judgment deficits in schizophrenia.

PMID- 20674281
TI  - The quest to identify heterogeneously resistant vancomycin-intermediate
      Staphylococcus aureus strains.
AB  - Definitive identification of heterogeneously resistant vancomycin-intermediate
      Staphylococcus aureus (hVISA) strains in the clinical microbiology laboratory has
      been an elusive goal for over a decade. Clinical data continue to affirm the
      importance of identifying hVISA strains in order to optimise antistaphylococcal
      therapy, especially for patients with infective endocarditis and other infections
      with high bacterial loads. Whilst the population analysis profile-area under the
      curve method can identify hVISA isolates with a high degree of accuracy, this
      method is not amenable to routine use in a clinical microbiology laboratory.
      Other methods to identify hVISA isolates lack sensitivity and/or specificity.
      Thus, the quest continues.

PMID- 20674282
TI  - In vitro activity of isavuconazole against 140 reference fungal strains and 165
      clinically isolated yeasts from Japan.
AB  - The in vitro susceptibilities of 140 laboratory reference strains of fungi,
      including type strains, and 165 clinical yeast isolates from Japan towards
      isavuconazole compared with fluconazole (FLC), itraconazole (ITC), voriconazole
      and amphotericin B were measured. Broth microdilution methods based on Clinical
      and Laboratory Standards Institute (CLSI) methods were used for yeasts, and RPMI
      MOPS medium semi-solidified with 0.2% low-melting-point agarose based on CLSI
      guidelines was used for moulds. The range of isavuconazole minimum inhibitory
      concentrations (MICs) was 0.0004-0.21 mg/L for Candida albicans, 0.0036-0.4 mg/L
      for Candida glabrata, 0.023-0.058 mg/L for Candida krusei, 0.0026-0.032 mg/L for
      Cryptococcus neoformans, 0.1-0.39mg/L for Aspergillus fumigatus and 0.2-0.39 mg/L
      for Aspergillus terreus. Isavuconazole was as active as ITC against the dimorphic
      true pathogenic fungi, with a range of MICs from <0.0004 mg/L to 0.0063 mg/L for
      Blastomyces dermatitidis and Histoplasma capsulatum. It was also active against
      uncommon dematiaceous fungi such as Exophiala spp. and Phialophora spp. as well
      as against dermatophytic species. Isavuconazole showed very good in vitro
      antifungal activity with a broad spectrum, including against FLC-resistant
      Candida spp., Aspergillus spp. and uncommon opportunistic fungal species. This is
      the first report of the in vitro susceptibility of Japanese clinical yeast
      isolates to isavuconazole. No cross-resistance was found to isavuconazole amongst
      FLC-resistant strains.

PMID- 20674283
TI  - Macrolide-resistant Mycoplasma pneumoniae in adults with community-acquired
      pneumonia.

PMID- 20674284
TI  - Post-antibiotic effect (PAE) of moxifloxacin in multidrug-resistant
      Stenotrophomonas maltophilia.

PMID- 20674285
TI  - Susceptibility of Klebsiella pneumoniae clinical isolates from 2007 to 2009 to
      colistin and comparator antibiotics.

PMID- 20674286
TI  - Dopaminergic modulation of the default mode network in Parkinson's disease.
AB  - Default mode network (DMN) is characterized by a deactivation of several cortical
      areas (including medial prefrontal cortex and posterior cingulate cortex) during
      goal-directed experimental tasks. Few findings are reported on DMN and the
      involvement of dopaminergic medication on this network in Parkinson's disease
      (PD). To evaluate the effect of levodopa on DMN deactivation, we conducted a
      randomized, crossover, placebo-controlled experiment consisting of two fMRI
      assessments in fourteen non-demented, non-depressed PD patients compared to
      thirteen healthy volunteers. They received either acute doses of levodopa or
      placebo in two fMRI sessions. Brain deactivation was evaluated during a facial
      emotion recognition task. While the control subjects showed a classical brain
      deactivation pattern during the emotional task, the PD patients taking placebo
      only deactivated the ventral medial prefrontal cortex. Patients failed to
      deactivate the posterior midline and lateral parts of DMN network. After levodopa
      administration, this network was restored conjointly with the improvement of
      motor dysfunction in PD patients. The levodopa effect on DMN is probably the
      consequence of a beneficial dopamine (DA) medication effect which leads to a fine
      tuning of the dopamine level in the motor part of striatum, resulting to a global
      improvement of physical state of PD patients and consequently an increased
      attentional resource to external stimuli. The absence of medial prefrontal
      deactivation impairment may suggest a preserved mesocortical DA system in these
      patients.

PMID- 20674287
TI  - Biocompatible novel starch/polyaniline composites: characterization, anti
      cytotoxicity and antioxidant activity.
AB  - Starch/polyaniline composites have been synthesized using oxidative
      polymerization of polyaniline in an aqueous dispersion of starch isolated from
      Colocasia esculenta corm. Scanning electron micrographs reveals the growth of
      polyaniline over the surface of the starch granules. DPPH scavenging and
      haemolysis prevention assay have been performed to estimate the antioxidant
      activity and cytotoxicity of the composites. Formation of new properties of the
      composites as compared to starch and poloyaniline was evident from the X-ray
      diffraction analysis (XRD). Characterization done using UV-Vis, FTIR and DSC
      analysis provide evidence of composite formation. Composite possesses antioxidant
      nature which increases with the concentration of polyaniline. The haemolysis
      prevention activity of these novel composite materials is found to increase as
      compared to the pure polyaniline with minor compromise in the antioxidant
      activity. The materials show tremendous potential for biomedical applications.

PMID- 20674288
TI  - Functionalization of gold nanoparticles with amino acid, beta-amyloid peptides
      and fragment.
AB  - Gold nanoparticles (Au NPs) were functionalized by cysteine (Cys), beta-amyloid
      peptides (Cys(0)Abeta(1-28), Cys(0)Abeta(1-40), Abeta(1-42)) and a pentapeptide
      fragment (Leu-Pro-Phe-Phe-Asp-OH (LPFFD-OH)). Optical absorption spectra of these
      systems were recorded and the plasmon resonance maximum values (lambda(max)) of
      the UV-vis spectra together with the transmission electron microscopy (TEM)
      images were also analysed. Both TEM images and the appearance of a new absorption
      band between approximately 720 and 750 nm in the visible spectra of the Au
      cysteine and Au-LPFFD-OH systems most probably indicate that upon addition of
      these molecules to Au NPs-containing aqueous dispersions formation of aggregates
      is occurred. The wavelength shift between the two observed absorption bands in
      cysteine- and pentapeptide-modified Au NPs systems are Deltalambda=185 and 193
      nm, respectively. These results suggest that the monodisperse spherical gold
      nanoparticles were arranged to chained structure due to the effect of these
      molecules. For confirmation of the binding of citrate and cysteine onto the
      plasmonic metal surface (1)H NMR measurements were also performed. (1)H NMR
      results may suggest that the citrate layer on the metal surface is replaced by
      cysteine leading to a formation of organic double layer structure. In the
      presence of beta-amyloid peptides the aggregation was not observed, especially in
      the Au-Cys(0)Abeta(1-40) and Au-Abeta(1-42) systems, however compared to the
      cysteine or LPFFD-OH-containing gold dispersion with Cys(0)Abeta(1-28) measurable
      less aggregation were occurred. The spectral parameters clearly suggest that
      Abeta(1-42) can attach or bind to the surface of gold nanoparticles via both the
      apolar and the N-donors containing side-chains of amino acids and no aggregation
      in the colloidal gold dispersion was observed.

PMID- 20674289
TI  - Nanomicelle with long-term circulation and enhanced stability of camptothecin
      based on mPEGylated alpha,beta-poly (L-aspartic acid)-camptothecin conjugate.
AB  - To enhance the stability and long-term circulation of camptothecin (CPT),
      mPEGylated alpha,beta-poly (L-aspartic acid)-CPT conjugates were synthesized, and
      used to fabricate nanomicelle. Firstly, alpha,beta-poly (L-aspartic acid)
      derivative (PAA-der) containing alkyne groups was synthesized via the ring
      opening of PSI with propargyl amine. And then, azide-functionalized CPT
      derivatives (CPT-N(3)) and azide-terminated poly (ethylene glycol) methyl ether
      (mPEG-N(3)) were conjugated with PAA-der by click cycloaddition to give mPEG
      graft-PAA-CPT conjugates. The formation of mPEG-graft-PAA-CPT nanomicelles was
      confirmed by fluorescence spectrophotoscopy and particle size measurements. It
      was found that all the nanomicelles showed spherical shapes with size about 178
      nm. MPEG-graft-PAA-CPT nanomicelles showed good storage stability, even
      incubation at 37 degrees C for 60 days, and improved the stability of CPT lactone
      form in aqueous media. A steady release rate of CPT was kept for 72h, suggested
      the great potential of mPEG-graft-PAA-CPT nanomicelles as polymer prodrug of CPT.

PMID- 20674290
TI  - Polymerization of catechin catalyzed by Mn-, Fe- and Al-oxides.
AB  - The role of short-range order (SRO) metal oxides, which are common in acid soils
      and associated environments, in influencing the abiotic transformations of
      catechin, which is common in the soil of tea plantations, still remains poorly
      understood. The aim of this study was to investigate the catalytic power of SRO
      Mn(IV)-, Fe(III)- and Al-oxides in influencing the abiotic transformations of
      catechin. At the end of a 90-h reaction period, the release of CO(2) in all the
      oxide-catechin systems is higher than that for the system with only catechin.
      Polymerization of catechin is catalyzed and enhanced by SRO-oxides, as is
      indicated by the absorbance values of the supernatants, which were obtained via
      visible adsorption spectroscopy, and the yields of humic polymers. The sequence
      of the oxides that increased the yield of total humic polymers in these systems
      under ambient atmosphere is: Fe(III)-oxide>Mn(IV)-oxide>Al-oxide>>no catalyst
      (catechin). The electron spin resonance (ESR) and Fourier transformation infrared
      absorption spectrometry (FT-IR) of humic polymers formed in the oxide-catechin
      systems were similar to the spectra obtained from the humic polymers extracted
      from the soil. The catalytic power of SRO-oxides in promoting the oxidative
      polymerization of catechin, the resultant formation of humic substances, and C
      turnover in acid soils thus merit attention.

PMID- 20674291
TI  - Glucosamine HCl as a new carrier for improved dissolution behaviour: effect of
      grinding.
AB  - The co-grinding technique is one of the most effective methods for improving the
      dissolution rate of poorly water-soluble drugs and it is superior to other
      approaches from an economical as well as an environmental stand point, as the
      technique does not require any toxic organic solvents. The present work is an
      attempt to use d-glucosamine HCl (G-HCl) as a potential excipient to improve
      dissolution rate of carbamazepine (CBZ) from physical mixtures and co-grinding
      formulations. The effect of order of grinding on dissolution of CBZ was also
      investigated. Co-ground of drug and G-HCL were prepared using different ratios
      using ball mill. The samples were subjected to different grinding times. In order
      to investigate the effect of grinding process on dissolution behaviour of CBZ,
      the drug was ground separately in the absence of glucosamine. Then the mixture of
      ground CBZ and un-ground d-glucosamine HCl were prepared. Physical mixtures of
      CBZ and G-HCl were also prepared for comparison. The properties of prepared co
      ground systems and physical mixtures were studied using a dissolution tester, FT
      IR, SEM, XRPD, and DSC. These results showed that the presence of glucosamine can
      increase dissolution rate of CBZ compared to pure CBZ. The results showed the
      order of grinding had a big impact on the dissolution performance of CBZ
      formulations containing glucosamine. All dissolution profiles generally showed
      that the fastest dissolution rate was obtained when ground CBZ was mixed with un
      ground glucosamine. This was closely followed by the co-grinding of CBZ with
      glucosamine where lower grinding times showed the fastest dissolution. XRPD
      showed that the grinding of CBZ can reduce the percentage crystallinity of drug
      crystals. DSC study of ground CBZ showed that the grinding induced polymorphism
      transformations in the CBZ crystals and the limit and type of these
      transformations were related to the grinding time.

PMID- 20674292
TI  - Optimization of the hydrophobic domain in poly(ethylene oxide)-poly(varepsilon
      caprolactone) based nano-carriers for the solubilization and delivery of
      Amphotericin B.
AB  - The aim of the study was to develop a polymeric nano-carrier based on methoxy
      poly(ethylene oxide)-b-poly(epsilon-caprolactone) (MePEO-b-PCL) for the optimum
      solubilization and delivery of Amphotericin B (AmB). For this purpose, MePEO-b
      PCL block co-polymers containing palmitoyl substituent on PCL (at a 100%
      substitution level) were synthesized through preparation of substituted monomer,
      that is, alpha-palmitoyl-epsilon-caprolactone, and further ring opening
      polymerization of this monomer by methoxy PEO (5000 g mol(-1)) using stannous
      octoate as catalyst. Prepared block co-polymers were characterized for their
      molecular weight by (1)H NMR and gel permeation chromatography, and assembled to
      polymeric nano-carriers. The self-assembly of synthesized MePEO-b-PPaCL to
      spherical particles of nanometer size range was shown by dynamic light scattering
      (DLS) and transmission electron microscopy (TEM). The efficacy of nano-carriers
      formed from this structure (abbreviated as MePEO-b-PPaCL) in comparison to
      unmodified MePEO-b-PCL and those with benzyl and cholesteryl substituent on PCL
      (abbreviated as MePEO-b-PBCL and MePEO-b-PChCL, respectively) on the
      solubilization and hemolytic activity of AmB against rat red blood cells was
      assessed. Under identical conditions, the maximum solubilization of AmB was
      achieved by nano-carriers prepared from MePEO-b-PPaCL (436 microg/mL), followed
      by MePEO-b-PChCL (355 microg/mL), MePEO-b-PBCL (296 microg/mL) and MePEO-b-PCL
      (222 microg/mL). The hemolytic activity of AmB was reduced the most by its
      encapsulation in MePEO-b-PChCL nano-particles which showed only 7% hemolysis at
      30 microg/mL AmB concentration. This was followed by MePEO-b-PCL nano-particles
      which illustrated 15% hemolysis, MePEO-b-PPaCL with 40% hemolysis and MePEO-b
      PBCL with 60% hemolysis at 30 microg/mL AmB concentrations, respectively. In
      contrast Fungizone showed 90% hemolysis at 30 microg/mL AmB concentration. Based
      on the improved solubility and reduced hemolytic activity, the MePEO-b-PChCL nano
      carriers are considered as optimum structures for AmB delivery.

PMID- 20674293
TI  - Characterization of hybrid bilayer membranes on silver electrodes as
      biocompatible SERS substrates to study membrane-protein interactions.
AB  - Hybrid bilayer lipid membranes (HBMs) were built on roughened silver electrodes
      exhibiting surface-enhanced Raman scattering (SERS) activity. The HBM consisted
      of a first layer of octadecanethiol (ODT) directly bound to the electrode
      surface, on which a second layer of 1,2-diphytanoyl-sn-glycero-3-phosphocholine
      (DPhPC) was obtained by self-assembled phospholipid vesicle fusion. The
      electrochemical properties of the HBM were investigated in situ by cyclic
      voltammetry (CV), AC voltammetry and electrochemical impedance spectroscopy
      (EIS). The results indicate that our HBMs are well-formed, and their insulating
      properties are comparable to those observed for HBM supported by smooth metal
      substrates. The interaction between the bilayer and the human enzyme cytochrome
      P450 2D6 (CYP2D6) was investigated. Surface-enhanced resonance Raman scattering
      (SERRS) measurements in combination with AC and EIS, performed on the same
      electrode sample, proved that the CYP2D6 is immobilized on the HBM without
      evident alterations of its active site and without significant perturbations of
      the bilayer architecture. This study yields novel insights into the properties of
      HBMs built on roughened surfaces, providing in situ electrochemical
      characterization of a substrate which is suitable for studying peripheral
      membrane proteins with SERRS spectroscopy.

PMID- 20674294
TI  - Investigating the effects of sodium dodecyl sulfate on the aggregative behavior
      of hen egg-white lysozyme at acidic pH.
AB  - The research presented here is aimed at examining the effects of sodium dodecyl
      sulfate on the aggregative behavior of hen egg-white lysozyme at pH 2.0. Through
      various spectroscopic techniques, dynamic light scattering, and electron
      microscopy, we first demonstrated that SDS exhibited a biphasic effect on
      lysozyme fibrillation. The presence of SDS at higher concentrations (e.g., 0.25,
      5.00, or 20.00 mM SDS) was found to suppress fibril formation of lysozyme whereas
      fibrillogenic lysozyme-SDS ensemble containing beta-sheet-rich conformation was
      observed upon the addition of lower concentrations of SDS (e.g., 0.00, 0.06, or
      0.1mM SDS). Next, our equilibrium urea-unfolding data revealed that lysozyme
      samples with higher SDS concentrations showed superior thermodynamic stabilities
      over the ones with no or lower levels of SDS. Finally, the correlation between
      SDS concentration and lysozyme aggregative/fibrillogenic propensity and the
      underlying interacting mechanism were further explored using surface tensiometry
      and isothermal titration calorimetry. We believe the outcome from this work may
      not only help decipher the molecular mechanism of amyloid fibrillation, but also
      shed light on a rational design of potential therapeutic strategies for amyloid
      pathology.

PMID- 20674295
TI  - Surfactants and ureas affect the cloud point of amphiphilic drug, clomipramine
      hydrochloride.
AB  - Clomipramine hydrochloride (CLP) is an antidepressant drug which shows
      temperature dependent phase separation, also known as the cloud point (CP).
      Increase in pH decreases the CP of the drug solution. Addition of ureas/thioureas
      at a fixed pH (6.25) decreases/increases the CP. In ureas, presence of >CO bond
      causes a decrease in repulsions among positively charged drug molecules. However,
      >CS bond (of thioureas) behaves oppositely and hence CP increases. Cationic and
      non-ionic surfactants form mixed micelles and hence increase the CP. Anionic
      surfactants, at low concentrations, retard micellization and increase the CP. At
      higher concentrations, these surfactants also form mixed micelles and, due to
      charge opposite to the drug molecules, reduce the repulsion among micelles and
      act as CP suppressors. Increase in solution pH/drug concentration at different
      fixed concentrations of CTAB causes the CP to decrease/increase. Dye
      solubilization results with the drug have provided proof to the above
      explanation.

PMID- 20674296
TI  - Significant effect of polar head group of surfactants on the solubilization of
      Zein in mixed micellar (SDS-DDAB) media.
AB  - In recent years, the ability of ionic surfactants such as sodium dodecyl sulfate
      (SDS) to solubilize the water-insoluble protein Zein in aqueous solution,
      referred to as the Zein solubilization test, has been investigated to rank the
      skin irritation potential and protein denaturation potential of surfactants.
      However, the potential of cationic surfactants towards solubilization of Zein has
      not been explored much. In present report, the effect of the concentration of
      cationic surfactant, dodecylethyldimethylammonium bromide (DDAB) on Zein
      solubilization in the presence of anionic surfactant, SDS has been investigated.
      It has been observed that the solubilization of the Zein protein induced by SDS
      is affected by the presence of DDAB. The electrostatic and hydrophobic
      interactions between two surfactants are the deciding factors for the
      solubilization of Zein. The estimated values of critical aggregation
      concentration (cac) and critical micellization concentration (cmc) indicate that
      the association of Zein with SDS-DDAB takes place at somewhat higher
      concentration than with SDS. Fluorescence study reveals the more hydrophobic
      environment for the pyrene in SDS-DDAB in Zein than SDS-DDAB in water. The
      aggregation behavior of mixed surfactants in the presence of protein has also
      been analyzed. Thermodynamic study of the colloidal behavior of mixed surfactants
      depicts that at higher temperature enthalpy factor as well as entropic factor
      increases however, increase in entropy dominates over enthalpy factor.

PMID- 20674297
TI  - MnO2 nanostructures of different morphologies from amino acids-MnO4- reactions in
      aqueous solutions.
AB  - In this paper, we describe a simple method for the synthesis of MnO(2)
      nanostructures (quantum dots) by permanganate oxidations of methionine and
      cysteine. Upon addition of permanganate to a solution of reductant (methionine
      and/or cysteine), yellow-brown color species appears within the time of mixing
      which was stable for several weeks. The UV-vis spectroscopy and transmission
      electron microscopy (TEM) techniques were used to characterize the nature of
      color formed. TEM images show that the MnO(2) sol consists of aggregated
      spherical nonoparticles (size in the range ca<or=7 nm) of various forms. In
      addition, we observed the different morphologies of the MnO(2) nanostructures
      (MnO(2) nanoparticles, nanosheet, and fiber-like aggregated nanostructures) under
      different experimental conditions. The effect of various parameters, such as
      [H(+)], [MnO(4)(-)], and [reductants] was also investigated.

PMID- 20674298
TI  - Kinetics of coacervation transition versus nanoparticle formation in chitosan
      sodium tripolyphosphate solutions.
AB  - Chitosan (deacetylation=75-85%) and sodium tripolyphosphate (TPP) solutions were
      observed to undergo spontaneous coacervation transition or nanoparticle formation
      depending on the chitosan concentration and the volumetric mixing ratio
      [chitosan/TPP]. Three distinct conditions have been identified: (i)
      [chitosan]<or=0.5mg/ml, 0.5<or=[chitosan/TPP]<or=2 and pH<5.5, yields spontaneous
      coacervation, (ii) 0.5<or=[chitosan]<or=2.5mg/ml, [chitosan/TPP]>or=2 and
      3.5<pH<5.5, produces chitosan nanoparticles and (iii)
      0.5<or=[chitosan]<or=3mg/ml, 3<or=[chitosan/TPP]<or=6 and 5<pH<7.5, favors
      induced coacervation. Sizing done by TEM and dynamic light scattering studies
      revealed that chitosan nanoparticles had typical diameter in the range
      approximately 150-350 nm depending on polymer concentration and chitosan/TPP
      mixing ratio, which reduced by approximately 40% when polyethylene glycol (PEG)
      was added to these solutions. The long-time light scattering probing of the
      solutions revealed that residual interactions continuously produced soluble
      intermolecular complexes over extended period of time, a process that enabled the
      generation of coacervate droplets seamlessly. The coacervates (formed
      spontaneously or induced), and chitosan and chitosan-PEG nanoparticles, were used
      for encapsulating hydrophobic protein synthesis inhibitor model drug
      cycloheximide. The comparative in vitro release profiles in phosphate buffer and
      simulated intestinal fluid was monitored at 37 degrees C.

PMID- 20674299
TI  - First quinquennial review of intensity-modulated radiotherapy at St Bartholomew's
      Hospital, London.
AB  - Intensity-modulated radiotherapy (IMRT) is a relatively new technique of
      delivering external beam radiotherapy that is becoming increasingly available in
      the UK. This paper summarises the introduction and initial clinical work in IMRT
      over the period 2004-2009. Physics aspects of commissioning are described,
      including the development of a robust method of quality control using a sweeping
      gap test. Details of the organisational changes necessary to introduce IMRT are
      given. The clinical selection and practice in head and neck sites are described,
      together with promising early results on the maintenance of salivary flow after
      IMRT. A summary of research into optimal planning for pelvic cancer follows. The
      controversial areas of breast and paediatric IMRT are discussed with
      recommendations on practice. The potential for concomitant boost therapy is
      exemplified in the treatment of brain metastatic disease.

PMID- 20674300
TI  - Computed tomography-magnetic resonance image registration in radiotherapy
      treatment planning.
AB  - Magnetic resonance imaging (MRI) is being increasingly used in radiotherapy
      treatment planning (RTP). MRI has the potential to provide improved localisation
      of target volumes, leading to better tumour control rates and reduced normal
      tissue complications, due to capabilities including excellent soft-tissue
      discrimination and the ability to provide scans in which the image contrast is
      weighted according to different tissue properties. When computed tomography (CT)
      MRI image registration is deployed, MR's advantages are combined with CT's
      geometrical security and its ability to provide electron density information. The
      quality of CT-MRI image registration can be favourably influenced by aspects of
      scan acquisition, including patient positioning/immobilisation and scan
      protocols. Appropriate protocols can ameliorate the possible presence of MR
      spatial distortions and other artefacts, but quality assurance of scanning
      remains essential. Here, the methods and quality assurance of CT-MR image
      registration are discussed. Developments in MRI scanner technology are
      progressively offering advantages for RTP, in terms of the possibility of better
      matching of patient positioning versus CT in a greater range of anatomical
      regions, while allowing thinner slices for better image quality in reformatted
      orthogonal planes.

PMID- 20674301
TI  - Validity of self-reported abdominal obesity in Thai adults: a comparison of waist
      circumference, waist-to-hip ratio and waist-to-stature ratio.
AB  - BACKGROUND AND AIMS: Waist circumference (WC), waist-to-hip ratio (WHR) and waist
      to-stature ratio (WSR), being common proxy measures of abdominal obesity, are
      useful tools in epidemiologic studies, but little is known about their validity
      when the indices are derived from self-reported measurements. We determine and
      compare the validity of self-reported WC, WHR and WSR in order to identify the
      optimal index for use in epidemiologic surveys. METHODS AND RESULTS: Technician-
      and self-reported measurements of height, waist and hip circumference were
      obtained from 613 Thai adults (mean age 35 years). Regarding technician-reported
      measurements as reference, diagnostic test properties were derived and
      performances of the indices compared using receiver-operator-characteristic
      curves and the area-under-the-curve (AUC) analyses. There was good agreement
      between technician- and self-reported measurements for WC and WSR (concordance
      correlation coefficients ranged from 0.84 to 0.90) but not for WHR (0.50 in men,
      0.45 in women). The sensitivity and specificity of self-reported WC and self
      reported WSR as measures of abdominal obesity were superior to those of self
      reported WHR in both sexes. AUCs for WC and WSR were comparable (0.93 and 0.92,
      respectively, in men; 0.88 and 0.87 in women) and significantly higher than for
      WHR (0.80 in men; 0.76 in women; p<0.0001). CONCLUSION: WC and WSR derived from
      self-reported waist and height measurements are valid methods for determining
      abdominal obesity. Self-reported measurements should not be used to derive the
      WHR. In Asian populations, WSR may be the optimal index of abdominal obesity when
      measurements are derived from self-reports in epidemiologic surveys.

PMID- 20674302
TI  - Dietary patterns and the prevalence of metabolic syndrome in Korean women.
AB  - BACKGROUND AND AIMS: The role of dietary patterns in metabolic syndrome has not
      been adequately investigated in Asian women. We aimed to identify dietary
      patterns and to evaluate the cross-sectional relationship between dietary
      patterns and the prevalence of metabolic syndrome in Korean women. METHODS AND
      RESULTS: In a cross-sectional study of 4984 women aged 30-79 years, dietary
      patterns were derived from 16 food groups using factor analysis. Metabolic
      syndrome was defined based on the Adult Treatment Panel III of the National
      Cholesterol Education Program (ATPIII NCEP) criteria as having three or more risk
      factors using a modified obesity index. Logistic regression was used to estimate
      the association between dietary pattern and the prevalence of metabolic syndrome.
      Three dietary patterns (Western, healthy and traditional) were identified. Higher
      consumption of the healthy pattern was inversely associated with metabolic
      syndrome (OR [95% CI] for highest vs. lowest quartile: 0.58 [0.50-0.91]; P for
      trend = 0.012) and most components of metabolic syndrome. In a stratified
      analysis by menopausal status, the inverse association of the healthy dietary
      pattern and metabolic syndrome was statistically significant only among
      postmenopausal women (OR [95% CI] for highest vs. lowest quartile: 0.60 [0.40
      0.86]; P for trend = 0.004). The Western and traditional patterns showed no
      association with metabolic syndrome, but were related to some individual risk
      factors for metabolic syndrome. CONCLUSIONS: These results suggest that the
      healthy dietary pattern is associated with a reduced risk for metabolic syndrome
      in Korean women, particularly in postmenopausal women.

PMID- 20674303
TI  - Food selection based on high total antioxidant capacity improves endothelial
      function in a low cardiovascular risk population.
AB  - BACKGROUND AND AIMS: Oxidative stress has been advocated as a major cause for
      cardiovascular disease (CVD), and low plasma antioxidant concentrations are
      associated with endothelial dysfunction, the first step towards atherosclerosis.
      However, although the antioxidant content in fruits and vegetables may explain at
      least in part their protective effect against CVD, supplementation with
      antioxidant vitamins fails to improve endothelial function and reduce CVD risk.
      The aim of this study was to investigate the impact of a diet rich in
      antioxidants on endothelial function measured by flow-mediated dilatation (FMD)
      in volunteers at low cardiovascular risk. METHODS AND RESULTS: In a crossover
      trial, 24 subjects (13 women, mean age 61 +/- 3 years), received, in a randomised
      order, a 14-day high (HT) and a 14-day low (LT) antioxidant diets, with a 2-week
      wash-out (WO) in between. Both diets were comparable in daily portions of fruits
      and vegetables, and in alcohol, fibre and macronutrient intake, but differed in
      their total antioxidant capacity. Before and after each diet, anthropometrics,
      blood pressure, fasting plasma glucose, lipid profile, hepatic enzymes,
      circulating antioxidant concentrations, high sensitivity C-reactive protein (hs
      CRP) and FMD were assessed. FMD increased significantly during the HT diet
      compared to the LT (p < 0.000). FMD values were 2.3% higher after HT compared
      with LT (p < 0.001) after adjustment for age, gender and diet order. alpha
      tocopherol increased significantly (p < 0.05) and hs-CRP and of gamma
      glutamyltranspeptidase decreased significantly (p < 0.05 and p < 0.01,
      respectively) during the HT diet, compared with the LT diet. CONCLUSIONS: A short
      term HT diet improves endothelial function in volunteers at low cardiovascular
      risk, which may further reduce their risk of CVD.

PMID- 20674304
TI  - Glycaemic index and body fat distribution in children: the results of the ARCA
      project.
AB  - BACKGROUND AND AIMS: Various dietary factors may play a critical role in body
      weight regulation. Among them, the role of glycaemic index (GI) remains a subject
      of debate. The present study aimed at evaluating the association between dietary
      GI, body mass index (BMI) and body fat distribution in school children. METHODS
      AND RESULTS: 3734 Italian children (M/F = 1883/1851; age range 6-11 years) were
      cross-sectionally screened for anthropometry (BMI, waist circumference),
      lifestyle and clinical history (questionnaire) and dietary habits (1-year food
      frequency questionnaire). Energy and macronutrients intake, dietary GI and
      glycaemic load (GL) were calculated. GI was directly associated with age, waist
      and BMI z-scores, energy, fibre and carbohydrate intake (r: from 0.080 to 0.238,
      P < 0.001), and negatively with fat intake (r: -0.060, P < 0.0001). BMI, waist
      circumference, energy intake, carbohydrate, protein and fibre intake and GL
      significantly increased, whilst fat intake decreased, going up across quartiles
      of residuals of dietary GI. At linear regression analysis, GI was associated with
      BMI and waist z-scores independently of age, sex, parental overweight/obesity,
      parental education, and energy intake, protein, fat, carbohydrate, fibre and GL
      residuals. In particular, GI was the sole nutritional factor among those under
      investigation, significantly associated with waist circumference. Controlling for
      covariates, the risk of overweight/obesity or of central fat distribution was
      almost two-folds higher in the upper quartile in comparison to the lowest
      quartile of dietary GI. CONCLUSION: Dietary GI is an independent determinant of
      body fat distribution in children as well as of total adiposity.

PMID- 20674305
TI  - The third Italian National Food Consumption Survey, INRAN-SCAI 2005-06--part 1:
      nutrient intakes in Italy.
AB  - BACKGROUND AND AIMS: Italian National Food Consumption Survey, INRAN-SCAI 2005
      06, is the third national food consumption survey performed in Italy. This study
      describes energy and nutrient intakes in Italy. METHODS AND RESULTS: A national
      cross-sectional food consumption survey was conducted using consecutive 3-day
      food records between October 2005 and December 2006. A sample of 3323 males and
      females aged 0.1-97.7 years living in private households was investigated.
      Individual food records were converted into energy and nutrient intakes with the
      use of recently updated national food composition databases. For each subject,
      intakes of energy and of 27 nutrients were calculated, including six minerals
      (i.e., iron, calcium, phosphorus, magnesium, potassium and zinc) and 10 vitamins
      (i.e., thiamine, riboflavin, vitamin C, vitamin B6, retinol, beta-carotene,
      vitamin A as retinol equivalents (REs), vitamin E, vitamin D and vitamin B12. On
      average, 36% of calories appeared to derive from fat (11% from saturated fatty
      acids) and 45% from available carbohydrates (15% from soluble carbohydrates).
      CONCLUSIONS: The results of the INRAN-SCAI 2005-06 survey in terms of nutrient
      intakes provide an important piece of information for nutrition surveillance of
      the population and may also be used to identify priorities for further research.

PMID- 20674306
TI  - The APOA1/C3/A4/A5 cluster and markers of allostatic load in the Boston Puerto
      Rican Health Study.
AB  - BACKGROUND AND AIMS: The APOA1/C3/A4/A5 cluster encodes key regulators of plasma
      lipids. Interactions between dietary factors and single nucleotide polymorphisms
      (SNPs) in the cluster have been reported. Allostatic load, or physiological
      dysregulation in response to stress, has been implicated in shaping health
      disparities in ethnic groups. We aimed to determine the association between
      polymorphisms in the APOA1/C3/A4/A5 cluster with allostatic load parameters,
      alone, and in interaction with dietary fat intake in Puerto Ricans adults.
      METHODS AND RESULTS: Data on demographic and anthropometric measures, lifestyle
      behaviors, and medication use, as well as blood and urine samples for biomarker
      analysis, were obtained from participants of the Boston Puerto Rican Health Study
      (n=821, age 45-75 y). The 12 polymorphisms analyzed were not associated with
      allostatic load parameters. Significant interactions were observed between
      dietary fat intake and APOA1-75 in association with waist circumference (WC),
      (P=0.005), APOC3-640 with diastolic blood pressure (DBP), (P=0.003), and APOA4
      N147S and APOA5 S19W with systolic blood pressure (SBP), (P=0.001 and P=0.002,
      respectively). Puerto Ricans homozygous for the common allele of APOA1-75, APOA4
      N147S and APOA5 S19W had lower WC and SBP when consuming <31% of total fat from
      energy, than participants with the minor allele. Participants heterozygous for
      APOC3-640 had lower DBP at total fat intake >=31% from energy. CONCLUSION: SNPs
      in APOA1/C3/A4/A5, as modulated by dietary fat intake, appear to influence
      allostatic load parameters in Puerto Ricans.

PMID- 20674307
TI  - Comparison of physical and psychological status in younger and older overweight
      obese women.
AB  - BACKGROUND AND AIM: Obesity prevalence is noticeably growing, even in the
      elderly. Most of the studies concerning the impact of obesity in the elderly
      evaluated physical co-morbidities, whilst very few data are available on
      psychological co-morbidities in people >= 60 years of age. The present study
      aimed to compare anthropometrical measures, physical co-morbidities and
      psychosocial factors correlated with overweight and obesity in younger and
      elderly people. METHODS AND RESULTS: In 456 women in the age range of 18-59 years
      and 128 women in the age range of 60-80 years with body mass index (BMI) >= 25/kg
      m2, body weight, height and waist and hip circumferences were measured. The
      presence of co-morbidities such as osteoarthritis, hypertension, type 2 diabetes
      and hypercholesterolaemia was assessed. The Obesity Related Well Being 97
      Questionnaire (ORWELL 97), Body Uneasiness Test (BUT), Symptom Check List 90 (SCL
      90) and Binge Eating Scale (BES) tests were used to evaluate psychometric
      variables. BMI was not significantly different between younger overweight-obese
      subjects and older overweight-obese subjects, whereas waist circumference and
      waist-to-hip ratio (WHR) were significantly higher in the elderly.
      Osteoarthritis, hypertension and hypercholesterolaemia were significantly more
      frequent in the elderly. Older overweight-obese subjects had better scores in
      most of the psychometric questionnaires. CONCLUSIONS: Our results show that older
      overweight-obese subjects have generally more physical co-morbidities but a
      better psychological status than younger adults, despite similar BMI. These data
      may contribute to a better understanding of obesity consequences in the elderly
      and may help clinicians to differentiate obesity treatments in relation to
      patients' age.

PMID- 20674308
TI  - Reduction in generation of reactive oxygen species and endothelial dysfunction
      during postprandial state.
AB  - BACKGROUND AND AIMS: To characterise changes in generation of cellular reactive
      oxygen species (ROS) in healthy males during the postprandial state, and to
      analyse the influence of the postprandial state on endothelial ROS generation and
      endothelial dysfunction. METHODS AND RESULTS: Seventeen healthy subjects were
      recruited. Blood samples were collected in the fasting state and 2, 4, 6 and 8h
      after liquid-meal intake (composition: 25% fat, 55% dextromaltose and 14%
      protein), providing 40 gfat m(-2) body surface. Plasma lipids, apolipoproteins,
      glucose and insulin were measured during this period. Peripheral blood
      mononuclear cells (PBMCs) were isolated by density-gradient centrifugation. The
      influence of postprandial state on intracellular ROS generation was measured by
      two different methods in PBMCs and in a human immortalised endothelial cell line
      (ECV 304). Artery flow-mediated vasodilation (FMD) was used to evaluate the
      endothelial function, and oxygen consumption by PBMCs was measured. Reduced ROS
      generation was observed in all methods and cells during the postprandial period.
      FMD was impaired 8h after meal intake (23+/-6 vs. 13+/-2, P<0.05 vs. baseline).
      The consumption of oxygen was reduced in PBMCs (-14% into 2h, P<0.05 vs. baseline
      and -27% after 4h, P<0.01 vs. baseline). ROS generation was correlated with
      plasma lipids, insulin, apolipoproteins and oxygen consumption. CONCLUSIONS: In
      contrast to the previously reported elevation of postprandial oxidative stress,
      this study shows reduced ROS generation in PBMCs and in ECV 304. Data obtained in
      both cellular models suggest the existence of a protective response against
      plasma postprandial oxidative stress.

PMID- 20674309
TI  - Can the Mediterranean diet lower HbA1c in type 2 diabetes? Results from a
      randomized cross-over study.
AB  - BACKGROUND AND AIMS: To investigate the impact of a diet modeled on the
      traditional Cretan Mediterranean diet on metabolic control and vascular risk in
      type 2 diabetes. METHODS AND RESULTS: Twenty-seven subjects (47-77 yrs) with type
      2 diabetes were randomly assigned to consume either the intervention diet ad
      libitum or their usual diet for 12 weeks and then cross over to the alternate
      diet. Most of the meals and staple foods for the intervention diet were provided.
      Lipids, glycemic variables, blood pressure, homocysteine, C-reactive protein,
      plasma carotenoids and body composition (anthropometry and dual energy X-ray
      absorptiometry) were assessed at baseline, and at the end of both diet periods.
      Dietary adherence was monitored using plasma carotenoid and fatty acid (FA)
      analysis, complemented by diet diaries. Compared with usual diet, on the ad
      libitum Mediterranean intervention diet glycosylated haemoglobin fell from 7.1%
      (95% CI: 6.5-7.7) to 6.8% (95% CI: 6.3-7.3) (p=0.012) and diet quality improved
      significantly [plant:animal (g/day) food ratio increased from 1.3 (95% CI: 1.1
      1.5) to 5.4 (95% CI: 4.3-6.6) (p<0.001)], plasma lycopene and lutein/zeaxanthin
      increased (36% and 25%, respectively), plasma saturated and trans FAs decreased,
      and monounsaturated FAs increased. CONCLUSION: A traditional moderate-fat
      Mediterranean diet improves glycemic control and diet quality in men and women
      with well-controlled type 2 diabetes, without adverse effects on weight.

PMID- 20674310
TI  - Large brachial artery diameter and diabetes in post-menopausal women.
AB  - BACKGROUND AND AIM: Vascular remodelling is one of the possible compensatory
      mechanisms in response to artery wall injury. It was demonstrated that post
      menopausal women with carotid atherosclerosis had a larger brachial artery
      diameter (BAD) than women without carotid plaques. Therefore, it is possible to
      hypothesise that artery enlargement could be a marker of early atherosclerosis.
      To investigate the eventual association between carotid and brachial artery
      diameter and disease affecting the vascular wall, we performed a case-control
      study in post-menopausal women with or without type II diabetes mellitus. METHODS
      AND RESULTS: We enrolled 28 cases (with diabetes) and 56 controls (without
      diabetes) matched for age and carotid atherosclerosis presence and severity. On
      the t-test, women with diabetes showed significantly larger brachial and common
      carotid artery diameters and, as expected, higher plasma glucose level and
      homeostasis model assessment (HOMA) than women without diabetes. On the
      univariate analysis, only plasma glucose level results correlated to BAD in the
      whole sample. Multivariate analysis confirmed that diabetes was a good predictor
      of brachial and carotid artery diameter, while age, systolic blood pressure and
      triglycerides were correlated only to the carotid diameter. CONCLUSIONS: Our data
      confirm that vascular remodelling is a systemic process occurring in conditions
      related to atherosclerosis, such as type II diabetes. Indeed, artery diameter
      could be a marker of early response of vessel wall to injury.

PMID- 20674311
TI  - Acute resveratrol supplementation improves flow-mediated dilatation in
      overweight/obese individuals with mildly elevated blood pressure.
AB  - BACKGROUND AND AIMS: Flow-mediated dilatation of the brachial artery (FMD) is a
      biomarker of endothelial function and cardiovascular health. Impaired FMD is
      associated with several cardiovascular risk factors including hypertension and
      obesity. Various food ingredients such as polyphenols have been shown to improve
      FMD. We investigated whether consuming resveratrol, a polyphenol found in red
      wine, can enhance FMD acutely and whether there is a dose-response relationship
      for this effect. METHODS AND RESULTS: 19 overweight/obese (BMI 25-35 kg m(-2))
      men or post-menopausal women with untreated borderline hypertension (systolic BP:
      130-160 mmHg or diastolic BP: 85-100 mmHg) consumed three doses of resveratrol
      (resVidaTM 30, 90 and 270 mg) and a placebo at weekly intervals in a double
      blind, randomized crossover comparison. One hour after consumption of the
      supplement, plasma resveratrol and FMD were measured. Data were analyzed by
      linear regression versus log(10) dose of resveratrol. 14 men and 5 women (age 55
      +/- 2 years, BMI 28.7 +/- 0.5 kg m(-2), BP 141 +/- 2/89 +/- 1 mmHg) completed
      this study. There was a significant dose effect of resveratrol on plasma
      resveratrol concentration (P < 0.001) and on FMD (P < 0.01), which increased from
      4.1 +/- 0.8% (placebo) to 7.7 +/- 1.5% after 270 mg resveratrol. FMD was also
      linearly related to log(10) plasma resveratrol concentration (P < 0.01).
      CONCLUSION: Acute resveratrol consumption increased plasma resveratrol
      concentrations and FMD in a dose-related manner. This effect may contribute to
      the purported cardiovascular health benefits of grapes and red wine.

PMID- 20674312
TI  - Risk for cardiovascular events in an Italian population of patients with type 2
      diabetes.
AB  - BACKGROUND AND AIM: This study aims to analyse the risk of cardiovascular events
      in a local cohort of patients with type 2 diabetes, and to evaluate the
      prognostic accuracy of four algorithms used to estimate cardiovascular risk: the
      Framingham study, United Kingdom Prospective Diabetes Study (UKPDS), Riskard
      study and Progetto Cuore. METHOD AND RESULTS: We analysed clinical charts of the
      Diabetes Clinics of Modena for the period 1991-95. Patients in the age range of
      35-65 with type 2 diabetes and no previous cardiovascular disease were eligible.
      The incidence of new cardiovascular disease was compared with estimated rates
      deriving from the different functions. A stratification was obtained in subgroups
      at different cardiovascular risk, allowing comparison between the algorithms. A
      total of 1532 patients were eligible; women presented a worse cardiovascular risk
      profile. An absolute 10-year rate of cardiovascular events of 14.9% was observed.
      Comparing patients with events with event-free subjects, we found significant
      differences in systolic blood pressure, age at visit, smoking, high-density
      lipoprotein (HDL)-cholesterol, duration of diabetes, glycosylated haemoglobin
      (HbA1c) and co-morbidities. Comparing the estimated risk rate according to the
      different functions, Italian algorithms were more consistent with observed data;
      however, Progetto Cuore and Riskard show underestimation of events when applied
      to females. CONCLUSIONS: Estimation of cardiovascular risk is dependent on the
      algorithm adopted and on the baseline risk of the reference cohort. Functions
      designed for a specific population, including risk variables peculiar for
      diabetes, should be adopted to increase the performance of such functions which
      is clearly unsatisfactory at present.

PMID- 20674313
TI  - Influence of chylomicron remnants on human monocyte activation in vitro.
AB  - BACKGROUND AND AIMS: Atherosclerosis is known to be an inflammatory disease and
      there is increasing evidence that chylomicron remnants (CMR), the lipoproteins
      which carry dietary fats in the blood, cause macrophage foam cell formation and
      inflammation. In early atherosclerosis the frequency of activated monocytes in
      the peripheral circulation is increased, and clearance of CMR from blood may be
      delayed, however, whether CMR contribute directly to monocyte activation and
      subsequent egress into the arterial wall has not been established. Here, the
      contribution of CMR to activation of monocyte pro-inflammatory pathways was
      assessed using an in vitro model. METHODS AND RESULTS: Primary human monocytes
      and CMR-like particles (CRLP) were used to measure several endpoints of monocyte
      activation. Treatment with CRLP caused rapid and prolonged generation of reactive
      oxygen species by monocytes. The pro-inflammatory chemokines MCP-1 and IL-8 were
      secreted in nanogram quantities by the cells in the absence of CRLP. IL-8
      secretion was transiently increased after CRLP treatment, and CRLP maintained
      secretion in the presence of pharmacological inhibitors of IL-8 production. In
      contrast, exposure to CRLP significantly reduced MCP-1 secretion. Chemotaxis
      towards MCP-1 was increased in monocytes pre-exposed to CRLP and was reversed by
      addition of exogenous MCP-1. CONCLUSION: Our findings indicate that CRLP activate
      human monocytes and augment their migration in vitro by reducing cellular MCP-1
      expression. Our data support the current hypothesis that CMR contribute to the
      inflammatory milieu of the arterial wall in early atherosclerosis, and suggest
      that this may reflect direct interaction with circulating blood monocytes.

PMID- 20674314
TI  - Coronary artery disease, cerebral non-fatal ischemic stroke in retinal vein
      occlusion: an 8-yr follow-up.
AB  - Forty-five consecutive subjects (26M, 19F; mean age 54 +/- 14 yrs) with a
      diagnosed retinal vein occlusion (RVO), were followed-up for 8 yrs. As many as
      145 sex-age- and blood pressure-matched individuals (78M, 67F; mean age 54.4 +/-
      13.5 yrs), that did not experience any vascular event, served as controls. At the
      time of the RVO, controls and subjects did not differ as to hypercholesterolemia,
      hypertrigliceridemia, diabetes mellitus, smoking habits, inherited/acquired
      thrombophilia. At the follow-up completion, they differed as to statin
      consumption (p = 0.016). During the 8-yrs follow-up, in the control population,
      11 out of 145 (7.6%) subjects had experienced a major vascular event (8 coronary
      artery disease; 3 cerebral non-fatal ischemic stroke). In contrast, of the 45
      subjects with a history of RVO, as many as 10 (22.2%) had experienced a major
      vascular event: 4 coronary artery disease; 4 cerebral non-fatal ischemic stroke;
      2 cardiovascular + cerebrovascular event (p = 0.012). A prolonged antiplatelet
      treatment, prior to the major vascular event, was found in 5/45 cases (11.1%) vs
      23/145 (15.9%) controls (p = 0.63). In contrast, a long-lasting administration of
      anti-hypertensive drugs, to achieve a control of blood pressure, was found in
      83.4% of controls and only in 46.7% of cases (p < 0.0001). In conclusion, in a 8
      yr follow-up, coronary artery disease and/or non-fatal ischemic stroke were more
      common in subjects with a history of RVO than in a large setting of subjects
      comparable for cardiovascular risk factors. These data also argue for RVO as a
      vascular disease in which aggressive anti-hypertensive therapy to prevent stroke
      and/or myocardial infarction is needed.

PMID- 20674315
TI  - Depression is associated with increased occurrence of left ventricle concentric
      geometry in older subjects independently of blood pressure levels.
AB  - BACKGROUND AND AIM: Depression is emerging as an independent risk factor for CV
      events, though mechanisms underlying this association are unknown. We
      investigated the relation between depression and LV hypertrophy (LVH) and LV
      structure in a group of elderly subjects. METHODS AND RESULTS: Three hundred
      seventy patients (mean age 79 +/- 6 years) were enrolled. CV risk factors were
      assessed. Depression was defined as a score >= 6 on the 15-item Geriatric
      Depression Scale. On the basis of the presence of LVH and of LV relative wall
      thickness (RWT) 4 echocardiographic patterns of LV adaptation were defined:
      concentric LVH (LVH with increased RWT); eccentric LVH (LVH with normal RWT);
      concentric LV remodeling (no LVH with increased RWT); normal LV (no LVH with
      normal RWT). Prevalence of hypertension was approximately 86% and 24.7% had
      diabetes (n.s. depressed vs not depressed subjects). BP was comparable in these
      two groups (134.7 +/- 1.4 vs 135.3 +/- 1.8 mmHg, 77.1 +/- 0.8 vs 76.3 +/- 1.0
      mmHg for SBP and DBP respectively). Depressed subjects (n = 165) showed a
      significantly higher occurrence of concentric LVH than not depressed, after
      adjustment for age, sex, and hypertension. Depression was associated with a 2.1
      fold higher risk of showing a LV concentric, either remodeling or LVH, pattern
      after adjustment for age, sex, and traditional CV risk factors. CONCLUSIONS:
      Depression is accompanied by a higher occurrence of concentric LVH in elderly
      subjects, independently of BP levels.

PMID- 20674316
TI  - Hyperglycemic and stressogenic effects of monocrotophos in rats: evidence for the
      involvement of acetylcholinesterase inhibition.
AB  - The purpose of this study was to investigate the involvement of
      acetylcholinesterase (AChE) inhibition in hyperglycemic and stressogenic effects
      of monocrotophos in rats. Oral administration of monocrotophos (1.8 mg/kg b.w.,
      1/10 LD(50)) caused reversible hyperglycemia in rats with peak increase occurring
      at 2 h following administration. The hyperglycemic outcome at 2 h was accompanied
      by significant inhibition of acetylcholinesterase (AChE) activity in brain (84%),
      adrenal (68%) and liver (53%) and stressogenic effects as revealed by marked
      increase in plasma corticosterone (102%) and liver tyrosine aminotransferase
      (TAT) (104%) activity. At 4 h following administration, there was normalization
      of hyperglycemia and hypercorticosteronemia, marginal attenuation of liver TAT
      activity and marked increase in liver glycogen content, without spontaneous
      reactivation of AChE activity in the organs studied. Interestingly, pre-treatment
      of rats with acetylcholine (ACh) receptor antagonists-atropine sulfate and methyl
      atropine nitrate offered significant protection against hyperglycemia,
      hypercorticosteronemia and increased liver TAT activity induced by monocrotophos.
      Our results clearly demonstrate the involvement of AChE inhibition in
      hyperglycemia and stressogenic effects of monocrotophos in rats following acute
      exposure. Protection offered by both, general and peripheral ACh antagonists
      provide further evidence for the involvement of peripheral AChE inhibition in the
      monocrotophos-induced effects.

PMID- 20674317
TI  - Male and female NOD mice differentially express peroxisome proliferator-activated
      receptors and pathogenic cytokines.
AB  - The peroxisome proliferator-activated receptors (PPARs) have been implicated in
      regulating the immune response. We determined the relative changes in the
      transcriptional expression of PPAR isoforms (alpha, gamma1 and gamma2) and
      cytokines involved in the pathogenesis of type 1 diabetes (T1D) in the immune
      cells of 5 weeks, 10 weeks and diabetic male non-obese diabetic (NOD) mice
      compared to those of female NOD mice from our previous studies, "normalized"
      against their respective non-obese diabetic resistant (NOR) mice controls.
      Overall PPARalpha was significantly more elevated in the macrophages of female
      NOD mice of all age groups whereas PPARgamma, particularly the PPARgamma2 isoform
      was more depressed in the macrophages and CD4(+) lymphocytes of female NOD mice
      compared to their male counterparts. The pro-inflammatory cytokines, IL-1 and
      TNFalpha, as well as the Th1 cytokines, IL-2 and IFNgamma were more elevated in
      female NOD mice whereas the Th2 cytokine, IL-4, was more depressed in these mice
      compared to their male counterparts. These findings suggest that the
      preponderance of T1D in female NOD mice may be influenced by the more pronounced
      changes in the expression of PPAR isoforms and pathogenic cytokines compared to
      those in male NOD mice.

PMID- 20674318
TI  - Lowering of platelet aggregation and serum eicosanoid levels in rats fed with a
      diet containing coconut oil blends with rice bran oil or sesame oil.
AB  - The present investigation was undertaken to study the effects of feeding a diet
      containing blended and interesterified fat to rats on thrombotic parameters such
      as platelet aggregation and eicosanoid levels in blood serum. Male Wistar rats
      were fed with a diet containing 10% fat from native; coconut oil (CNO), rice bran
      oil (RBO), sesame oil (SESO), blended; (CNO+RBO blend (B), CNO+SESO(B), or
      interesterified oils; CNO+RBO interesterified (I), CNO+SESO(I) for a period of 60
      days. Rats given a diet containing blended oil of CNO+RBO(B) or CNO+SESO(B)
      showed a decrease in rate of ADP induced aggregation of platelets by 34% and 30%,
      respectively, compared to those fed with CNO. Aggregation induced by collagen was
      also reduced similarly in rats given blended or interesterified oils of CNO with
      RBO or SESO. Feeding interesterified oil CNO+RBO(I), and CNO+SESO(I) to rats also
      resulted in decrease in rate of ADP induced platelet aggregation by 37% and 34%,
      respectively, compared to rats fed with CNO. The prostacyclin/thromboxane ratio
      in serum was increased in rats fed with blended and interesterified oil compared
      to those fed with CNO. These results indicated that CNO when blended or
      interesterified with RBO or SESO exhibit antithrombotic effects as compared to
      the effect observed by feeding rats with CNO.

PMID- 20674319
TI  - Immune senescence.

PMID- 20674320
TI  - Immune memory and aging: an infinite or finite resource?
AB  - Recent developments in the field of immune memory research and the accumulating
      literature on age-related alterations in homeostasis, primary and memory T cell
      responses make it pertinent to address whether and how memory responses are
      affected by aging with regard to their generation, maintenance, and protective
      function. New knowledge of T cell repertoire maintenance over long periods of
      time, particularly when confronted with persistent pathogen challenge, is now
      enriched further by studies on whether recent immunological memory can 'overfill'
      and/or constrict prior memory responses. Along with studies on potentiation of
      memory responses by dietary/metabolic interventions and the recent advances on
      regulation of primary responses with aging, these findings provide a platform for
      new approaches to vaccination of older adults.

PMID- 20674322
TI  - CT lung densitometry in young adults with alpha-1-antitrypsin deficiency.
AB  - BACKGROUND: Severe (PiZZ) and moderate (PiSZ) alpha-1-antitrypsin (AAT)
      deficiency predispose to lung emphysema, especially in smokers. We hypothesized
      that multi-slice computed tomography (CT) might be superior to pulmonary function
      tests (PFT) to detect lung emphysema in AAT-deficient individuals at the age of
      32 years. METHODS: A subgroup of PiZZ and PiSZ individuals identified during the
      Swedish newborn screening programme in 1972-74 underwent multi-slice CT and PFT
      at the age of 32 years. From the CT scans the percentile density at 15% (PD(15))
      and the relative area below -910 Hounsfield Units (RA(-910) HU) were calculated.
      The results of PFT and CT were compared between the AAT-deficient individuals and
      an age-matched control group. RESULTS: Twenty-five PiZZ, 11 PiSZ and 17 PiMM
      individuals participated in the study. All Pi subgroups had normal lung function.
      The mean PD(15) was 81 (SD 22) g/L in the PiZZ individuals, 96 (SD 35) g/L in the
      PiSZ individuals and 79 (SD 17) g/L in the PiMM individuals (ns), and the RA-910
      were 30 (SD 18)%, 24 (SD 20)%, and 32 (SD 18)%, respectively (ns). For the never
      smoker subgroups, in the PiZZ (n = 23), PiSZ (n = 8) and PiMM (n = 12), the mean
      PD(15) were 95 (SD 35) g/L, 81 (SD 22) g/L, and 75 (SD 12) g/L, respectively
      (ns). PD(15) was significantly correlated to CT derived lung size (r = -0.72; p <
      0.001). CONCLUSIONS: CT densitometry revealed no signs of emphysema and no
      differences between the AAT-deficient individuals identified by neonatal
      screening and age-matched control subjects.

PMID- 20674321
TI  - Inborn errors of mucocutaneous immunity to Candida albicans in humans: a role for
      IL-17 cytokines?
AB  - The various clinical manifestations of chronic mucocutaneous candidiasis (CMC)
      often result from acquired T-cell immunodeficiencies. More rarely, CMC results
      from inborn errors of immunity, the recent dissection of which has shed light on
      the molecular mechanisms of mucocutaneous immunity to Candida albicans. CMC may
      accompany various other infectious diseases in patients with almost any broad and
      profound T-cell primary immunodeficiency. By contrast, CMC is one of the few key
      infections in patients with autosomal dominant hyper IgE syndrome (mutations in
      STAT3), and in rare patients with autosomal recessive predisposition to
      mucocutaneous and invasive fungal infections (mutation in CARD9). In patients
      with mutations in STAT3 and CARD9, the development of IL-17-producing T cells is
      impaired. Moreover, CMC is the principal, if not only, infection in patients with
      autosomal recessive autoimmune polyendocrinopathy syndrome-I (mutations in AIRE).
      Patients with this condition have high titers of neutralizing autoantibodies
      (auto-Abs) against the IL-17 cytokines IL-17A, IL-17F, and IL-22. Collectively,
      these data suggest that human IL-17A, IL-17F, and IL-22 are essential for
      mucocutaneous immunity to C. albicans. They also suggest that the distinct
      syndrome of isolated CMC, without auto-immunity or other infections, may be
      caused by inborn errors of IL-17 immunity.

PMID- 20674323
TI  - Sorting of polypropylene resins by color in MSW using visible reflectance
      spectroscopy.
AB  - In this paper, an automated sorter is proposed for distinguishing polypropylene
      (PP) plastics based on their color. This sorting system uses visible (VIS)
      reflectance spectroscopy to separate PP resins according to their colors. A
      "Three-Filter" identification algorithm was developed to recognize the PP color
      (blue, red, green, white or yellow), and accordingly, give the command for
      throwing or not throwing PP to a series of electro pneumatic valves. The proposed
      sorting system was demonstrated to be fast and accurate, despite the presence of
      different labels and surface contamination on the PP resins.

PMID- 20674324
TI  - Greenhouse gas emissions from home composting of organic household waste.
AB  - The emission of greenhouse gases (GHGs) is a potential environmental disadvantage
      of home composting. Because of a lack of reliable GHG emission data, a
      comprehensive experimental home composting system was set up. The system
      consisted of six composting units, and a static flux chamber method was used to
      measure and quantify the GHG emissions for one year composting of organic
      household waste (OHW). The average OHW input in the six composting units was 2.6
      3.5 kg week(-1) and the temperature inside the composting units was in all cases
      only a few degrees (2-10  degrees C) higher than the ambient temperature. The
      emissions of methane (CH(4)) and nitrous oxide (N(2)O) were quantified as 0.4-4.2
      kg CH(4)Mg(-1) input wet waste (ww) and 0.30-0.55 kg N(2)OMg(-1)ww, depending on
      the mixing frequency. This corresponds to emission factors (EFs) (including only
      CH(4) and N(2)O emissions) of 100-239 kg CO(2)-eq.Mg(-1)ww. Composting units
      exposed to weekly mixing had the highest EFs, whereas the units with no mixing
      during the entire year had the lowest emissions. In addition to the higher
      emission from the frequently mixed units, there was also an instant release of
      CH(4) during mixing which was estimated to 8-12% of the total CH(4) emissions.
      Experiments with higher loads of OHW (up to 20 kg every fortnight) entailed a
      higher emission and significantly increased overall EFs (in kg substance per Mg(
      1)ww). However, the temperature development did not change significantly. The GHG
      emissions (in kg CO(2)-eq.Mg(-1)ww) from home composting of OHW were found to be
      in the same order of magnitude as for centralised composting plants.

PMID- 20674325
TI  - Colorimetric genotyping of single nucleotide polymorphism based on selective
      aggregation of unmodified gold nanoparticles.
AB  - We have developed a colorimetric method for genotyping of single nucleotide
      polymorphism (rs2131877) in 15 human DNA samples using selective aggregation of
      unmodified gold nanoparticles. First, we designed two different types of
      oligonucleotide probes with either thymine or cytosine at the end that are
      perfect complementary to the target allele sequence. After hybridization of the
      probe and target DNAs, the double-stranded DNA was added to the unmodified gold
      nanoparticle suspensions. By adjusting the salt concentration, we could induce
      aggregation of gold nanoparticles exclusively for the samples with the perfectly
      matched double-stranded DNAs, which resulted in a distinct color change of the
      suspension. This enabled us to discern samples with three different genotypes of
      the target sequences by naked eye: (i) the genotype with only T (thymine)
      alleles; (ii) that with only C (cytosine) alleles; (iii) that with both T and C
      alleles. We also confirmed these results by an independent direct sequencing
      method. These results suggest that the selective aggregation of unmodified gold
      nanoparticles can successfully be used to discern genotypes of single nucleotide
      polymorphisms.

PMID- 20674326
TI  - Lambda exonuclease pre-treatment for improved DNA-chip performance depends on the
      relative probe-target position.
AB  - The hybridisation characteristics of DNA targets to solid phase bound probes,
      e.g. in DNA microarrays, depend on the probe-target position and on target
      renaturation if a dsDNA target is used. We investigated a lambda exonuclease
      treatment of a PCR amplified dsDNA target to produce ssDNA with regard to probe
      target position, treatment duration and inactivation time towards its impact on
      fluorescence or electrical signals on two DNA-chip formats. Surprisingly, the
      achieved amplification factors varied by three orders of magnitude, i.e. 2-1074
      fold signal enhancement, depending on the relative probe-target position and
      readout scheme. The presented results can be used to design future studies
      involving lambda exonuclease preanalytic treatments.

PMID- 20674327
TI  - Nanoplasmonic biosensing with on-chip electrical detection.
AB  - A nanoplasmonic biosensor chip with integrated electrical detection is presented.
      The concept is based on the local refractive index sensitivity of nanoplasmonic
      gold nanodisks (110 nm in diameter and 20 nm in height) that are fabricated,
      through a parallel method, directly on an array of silicon solar cells or
      photoactive diodes. The nanoplasmonic properties of the sensor chip were
      investigated both optically and electrically, with excellent agreement between
      the two. We show that local changes in the refractive index of the surrounding
      environment gives changes in the nanoplasmonic properties of the gold nanodisks,
      which induce corresponding changes in the photocurrent at single wavelengths of
      the nanoplasmonic solar cells. With a simple light-emitting diode as light
      source, and together with a material-specific modification protocol, the
      photocurrent output of the nanoplasmonic sensor chip was successfully used to
      monitor a specific biorecognition reaction in real-time.

PMID- 20674328
TI  - An integrated photo-thermal sensing system for rapid and direct diagnosis of
      anemia.
AB  - This article presents a thermal biosensor to diagnose the anemia without chemical
      treatments using temperature increase of red blood cells (RBC) when hemoglobin
      molecules absorb specific wavelength of photons and convert them to thermal
      energy. For measuring temperature change of red blood cell, the micro-scaled
      platinum resistance temperature detector (Pt RTD) was developed. For maintenance
      of constant ambient temperature, we designed and fabricated a thermostat system.
      The thermostat system consists of a K-type thermocouple and two electric heaters
      that serve to increase the system temperature, which is monitored by the
      thermocouple. Both heaters and the thermocouple were connected to a proportional
      integral-derivative (PID) controller and enabled to maintain the temperature
      constant (<+/-0.1 degrees C). For specific heating of red blood cell, 8.0 W/cm(2)
      diode pumped solid state (DPSS) continuous wave (CW) laser module was used with
      532 nm wavelength. Using this system, we successfully measured the temperature
      variations (from 66.33+/-2.72 degrees C to 74.16+/-2.06 degrees C) of whole blood
      samples from 10 anemic patients and subsequently determined the concentration of
      hemoglobin (from 7.2 g/dL to 9.8 g/dL). The method proposed in this paper
      requires significantly less amount of whole blood sample (6 MUl) compared with
      the conventional methods (175 MUl) and allows instantaneous diagnosis (3 s) of
      anemia.

PMID- 20674329
TI  - Simultaneous electrochemical determination of superoxide anion radical and
      nitrite using Cu,ZnSOD immobilized on carbon nanotube in polypyrrole matrix.
AB  - A novel highly sensitive biosensor for the direct and simultaneous determination
      of superoxide anion radical (O2-) and nitrite (NO2-) was developed by
      incorporation of carbon nanotube (CNT) solubilized in nafion in polypyrrole (PPy)
      matrix on Pt electrode followed by immobilization of Cu,ZnSOD (SOD1) on it. The
      CNT/PPy nanocomposite electrode enhanced the immobilization of SOD1 and promoted
      the electron transfer of SOD1 minimizing its fouling effect. The surface
      morphological images of PPy and CNT-PPy nanocomposite on Pt electrode were
      obtained by scanning electron microscopy exhibiting highly microporous
      structures. The electrochemical behavior of the biosensor investigated by cyclic
      voltammetry revealed that the SOD1 immobilized electrode showed characteristic of
      SOD1 quasi-reversible redox peaks with a formal potential of +0.065 V vs.
      Ag/AgCl. The biosensor exhibited a linear response over the concentration range
      from 0.1 to 750 MUM, with a detection limit of 0.1+/-0.03 MUM for O2- and a
      corresponding linear range of 0.5-2000 MUM, with a detection limit of 0.5+/-0.025
      MUM for NO2-. In addition, the biosensor exhibited high sensitivity, good
      reproducibility and retained stability over 30 days. This modified electrode was
      quite effective not only in detecting O2- and NO2- independently but also
      determining the concentration of O2- and NO2- simultaneously in vitro and from
      cancer cells.

PMID- 20674330
TI  - An improved sensitivity nonenzymatic glucose biosensor based on a CuxO modified
      electrode.
AB  - An enzymeless biosensor based on CuxO/Cu electrode was investigated in this
      study. The XRD analysis confirmed that CuxO nanostructured material was composed
      of Cu2O and CuO. The FESEM images showed that the catalysts were flower-like with
      large surface area. From cyclic voltammograms, the peak current of CuxO/Cu
      electrode was 6, 6.3 and 1.7 times higher than that of the Cu foil, Cu2O/GCE and
      CuO/GCE electrodes, respectively. The biosensor based on CuxO/Cu exhibited
      excellent performance for glucose detection, giving a linear dependence between
      current and glucose concentration (R=0.996), with a low detection limit (0.049
      mM) and high sensitivity (1.62 mA cm(-2) mM(-1)). Finally, the CuxO/Cu sensor was
      applied and checked in the glucose determination in blood serum samples.

PMID- 20674331
TI  - Chemical vectors for gene delivery: uptake and intracellular trafficking.
AB  - Chemical vectors for non-viral gene delivery are based on engineered DNA
      nanoparticles produced with various range of macromolecules suitable to mimic
      some viral functions required for gene transfer. Many efforts have been
      undertaken these past years to identify cellular barriers that have to be passed
      for this issue. Here, we summarize the current status of knowledge on the uptake
      mechanism of DNA nanoparticles made with polymers and liposomes, their endosomal
      escape, cytosolic diffusion, and nuclear import of pDNA. Studies reported these
      past years regarding pDNA nanoparticles endocytosis indicated that there is no
      clear evident relationship between the ways of entry and the transfection
      efficiency. By contrast, the sequestration of pDNA in intracellular vesicles and
      the low number of pDNA close to the nuclear envelop are identified as the major
      intracellular barriers. So, intensive investigations to increase the cytosolic
      delivery of pDNA and its migration toward nuclear pores make sense to bring the
      transfection efficiency closer to that of viruses.

PMID- 20674332
TI  - Systems biology of apoptosis signaling networks.
AB  - Apoptosis is a complex but highly defined cellular program of cell demolition.
      Apoptosis can be triggered by the extrinsic or the intrinsic death pathways.
      Deregulation of apoptosis leads to a number of serious diseases, including
      cancer. A substantial progress in understanding apoptotic signaling networks has
      been recently achieved using systems biology. This review will give an overview
      of the contemporary models of apoptotic signaling networks. The potential of the
      dynamic models, which include all known components of the network, versus the
      importance of searching for new components of the networks using different
      screening techniques will be discussed. The further development of apoptotic
      signaling networks should provide ways to sensitize cells toward apoptosis and
      provide new therapies for cancer treatment.

PMID- 20674333
TI  - An international validation study of the EORTC QLQ-INFO25 questionnaire: an
      instrument to assess the information given to cancer patients.
AB  - AIM: The EORTC Quality of Life (QOL) Group has developed an instrument to
      evaluate the information received by cancer patients. This study assessed the
      psychometric characteristics of the EORTC INFO module in a large
      international/multi-cultural sample of cancer patients. METHODS: The provisional
      26-item information module (EORTC INFO26) was administered with the EORTC QLQ-C30
      and the information scales of the inpatient satisfaction module EORTC IN-PATSAT32
      on two occasions during the patients' treatment and follow-up period.
      Questionnaire-hypothesised scale structure, reliability, validity and
      responsiveness to changes were evaluated through standard psychometric analyses.
      Patient acceptability was assessed with a debriefing questionnaire. RESULTS: The
      study comprised 509 patients from 8 countries (7 European countries and Taiwan)
      with different cancers and disease stages. Multi-trait scaling analysis led to
      the deletion of one item but confirmed the hypothesised 4 multi-item scales
      (information about disease, medical tests, treatment and other services) and
      eight single items. Internal consistency for all scales was good (alpha>0.70), as
      was test-retest reliability (intraclass correlations>0.70). All items can be
      combined to generate a single score (alpha>0.90). Convergent validity was
      supported by significant correlations with related areas of IN-PATSAT32 (r>0.40).
      Low correlations with EORTC QLQ-C30 scales confirmed divergent validity (r<0.30)
      The EORTC INFO-25 module discriminated among groups based on gender, age,
      education, levels of anxiety and depression, information wishes and satisfaction.
      Only one scale captured changes over time. CONCLUSIONS: The EORTC QLQ-INFO 25 is
      a reliable and valid self-reported instrument. The module can be used in cross
      cultural observational and intervention studies.

PMID- 20674334
TI  - Interconversion of three measures of performance status: an empirical analysis.
AB  - PURPOSE: To construct empirically a conversion table to convert performance
      status scores among the Eastern Cooperative Oncology Group (ECOG), Karnofsky
      Performance Status (KPS) and Palliative Performance Scale (PPS) measures, using a
      large sample of patients with advanced cancer. METHODS: Seven physicians
      completed assessments on 1385 consecutive patients attending an oncology
      palliative care clinic, or admitted to an acute cancer palliative care unit. The
      three measures were distributed as a questionnaire package; the order in which
      they were presented was randomly assigned for each week. Scales were compared
      using the hit rate and the weighted kappa coefficient (kappa(w)). The KPS and PPS
      were compared directly; for comparisons of either scale with the ECOG, all 70
      possible categorisations of KPS and PPS were computed. An 'ideal' categorisation
      was selected based on maximisation of both statistical methods. RESULTS: The KPS
      and PPS matched in 1209 out of 1385 assessments (hit rate 87%; kappa(w) 0.97).
      For both the KPS and the PPS, the categorisation of 100 (ECOG 0), 80-90 (1), 60
      70 (2), 40-50 (3), 10-30 (4) had the highest hit rate (75%), and the second
      highest kappa(w) (0.84, p<0.0001). One other combination had a slightly higher
      kappa(w) (0.85 for both KPS and PPS), but a lower hit rate (73% for KPS, 72% for
      PPS). CONCLUSIONS: We have derived empirically a conversion scale among the ECOG,
      KPS and PPS scales. The proposed scale provides a means of translating amongst
      these measures, which may improve accuracy of communication about performance
      status amongst oncology clinicians and researchers.

PMID- 20674335
TI  - Predictors of outcome and methodological issues in children with acute
      lymphoblastic leukaemia in El Salvador.
AB  - BACKGROUND: Most children with cancer live in low-income countries (LICs) where
      risk factors in paediatric acute lymphoblastic leukaemia (ALL) developed in high
      income countries may not apply. METHODS: We describe predictors of survival for
      children in El Salvador with ALL. We included patients <16 years diagnosed with
      ALL between January 2001 and July 2007 treated with the El Salvador-Guatemala
      Honduras II protocol. Demographic, disease-related, socioeconomic and nutritional
      variables were examined as potential predictors of event-free survival (EFS) and
      overall survival (OS). RESULTS: 260/443 patients (58.7%) were classified as
      standard risk. Standard- and high-risk 5-year EFS were 56.3 +/- 4.5% and 48.6 +/-
      5.5%; 5-year OS were 77.7 +/- 3.8% and 61.9 +/- 5.8%, respectively. Among
      standard-risk children, socioeconomic variables such as higher monthly income
      (hazard ratio [HR] per $100 = 0.84 [95% confidence interval (CI) 0.70-0.99;
      P=0.04]) and parental secondary education (HR = 0.49, 95% CI 0.29-0.84; P = 0.01)
      were associated with better EFS. Among high-risk children, higher initial white
      blood cell (HR per 10*10(9)/L = 1.03, 95% CI 1.02-1.05; P<0.001) predicted worse
      EFS; socioeconomic variables were not predictive. The difference in EFS and OS
      appeared related to overestimating OS secondary to poor follow-up after
      abandonment/relapse. CONCLUSION: Socioeconomic variables predicted worse EFS in
      standard-risk children while disease-related variables were predictive in high
      risk patients. Further studies should delineate pathways through which
      socioeconomic status affects EFS in order to design effective interventions. EFS
      should be the primary outcome in LIC studies.

PMID- 20674336
TI  - Management and prevention of complications of subcutaneous intravenous infusion
      port.
AB  - Subcutaneous intravenous infusion port (SIIP) has become an increasingly and
      widely adopted technique in the management of oncology patients. This route has
      been used not only for chemotherapy but also for parenteral nutrition provision,
      blood transfusion, medication administration, blood sample collection,
      hemodialysis, and so on. This system provides a safe vascular access with low
      complication rate which helps preventing patients from vascular infection and
      catheter associated thrombosis. In this study, we reviewed 1247 cases of breast
      cancer patients that had subcutaneous intravenous infusion port implanted for
      chemotherapy in our general surgery department from 1990 to 2008. The result
      indicates that complication decreases as our technique and experience mature. We
      hereby share our accrued experience and improved technique, hoping to be of help
      to young surgeons.

PMID- 20674337
TI  - Impact of ammonia and sulphate concentration on thermophilic anaerobic digestion.
AB  - The effect of increasing concentrations of ammonia and sulphate on thermophilic
      anaerobic digestion (52 degrees C) was studied at laboratory-scale. The substrate
      consisted of a synthetic solution supplemented with ammonia and sodium sulphate.
      In terms of biogas production, the results showed that the C/N and C/SO(4)(2-)
      thresholds were 4.40 and 1.60, respectively, corresponding to 620 mg FA (free
      ammonia)/L and 1400 mg SO(4)(2-)/L. No reduction in biogas production was
      observed until reaching the above concentration of sulphate in the sulphate
      toxicity test. However, when the concentration of ammonia was increased to 620 mg
      FA/L in the ammonia toxicity test, a gradual decrease of 21% was observed for the
      biogas. In order to characterise each set of experiments kinetically, a biogas
      production first-order kinetic model was used to fit the experimental data. The
      proposed model accurately predicted the behaviour of the microorganisms affecting
      the thermophilic anaerobic digestion, allowing its evolution to be predicted.

PMID- 20674338
TI  - Eliminating inhibition of enzymatic hydrolysis by lignosulfonate in unwashed
      sulfite-pretreated aspen using metal salts.
AB  - This study demonstrated the efficiency of Ca(II) and Mg(II) in removing
      inhibition of enzymatic hydrolysis by lignosulfonate through non-productive
      adsorption of enzymes. Adding 1 mmol/g cellulose of either metal salt restores
      approximately 65% of the activity lost when a pure cellulose/cellulase solution
      is spiked with lignosulfonate. Addition of either Ca(II) or Mg(II) is also
      effective in counteracting soluble inhibitors of cellulase present in unwashed
      aspen solid substrate produced by SPORL (sulfite pretreatment to overcome
      recalcitrance of lignocelluloses). Soluble inhibitors are often removed by
      thoroughly washing the lignocellulosic solid substrate following pretreatment. It
      was determined that adding 1 mmol of MgSO(4)/g substrate (oven dry) to the
      unwashed aspen substrate gave enzymatic substrate digestibility (SED) equivalent
      to that of washing for a range of enzyme loadings. These results demonstrate that
      applying divalent metal salts eliminates the need for washing, thereby saving
      considerable process water and cost for production of chemicals and biofuels from
      lignocellulose.

PMID- 20674339
TI  - Enhancing fermentative hydrogen production from sucrose.
AB  - This study evaluated the hypothesis that fermentative hydrogen production from
      organic-rich feedstock could be enhanced by supplementing with waste materials
      such as cattle manure that could provide nutritional needs, buffering capacity,
      and native hydrogen-producing organisms. This hypothesis was tested in batch
      reactors fed with sucrose blended with cattle manure run at 25 degrees C without
      any nutrient supplements, pH adjustments, buffering, or gas-sparging. Hydrogen
      production rates in these reactors ranged 16-30 mL H(2)/g DeltaCOD-day, while
      hydrogen content in the biogases ranged 50-59%. Compared to literature studies
      conducted at higher temperatures, hydrogen yields found in this study at 25
      degrees C were higher in the range of 3.8-4.7 mol H(2)/mol sucrose added, with
      higher positive net energy yields (>14 kJ/L). This study demonstrated that cattle
      manure as a supplement could not only provide hydrogen-producing seed,
      nutritional needs, and buffering capacity, but also increase hydrogen yield by
      approximately 10%, improving the economic viability of fermentative biohydrogen
      production from sugary wastes.

PMID- 20674340
TI  - Effect of biodiesel glycerol type and fermentor configuration on mixed-acid
      fermentations.
AB  - The MixAlco process biologically converts biomass to carboxylate salts that may
      be converted to a variety of chemicals and fuels. This study examines the
      viability of different types of glycerol as a potential feedstock. Batch
      fermentations of crude biodiesel glycerol were compared to distilled and refined
      glycerol. Continuous fermentations were performed in a CSTR and a packed-bed
      fermentor with refined glycerol. While crude and distilled glycerol are difficult
      to process industrially, all types of glycerol performed well during MixAlco
      fermentations, producing acid concentrations above 22 g/L and conversions of
      greater than 65%. The CSTR configuration produced excellent acid concentrations
      (16 g/L) while the packed-bed configuration produced high amounts of cell
      material for use in cell extract products or starter cultures.

PMID- 20674341
TI  - Wastewater treatment high rate algal ponds for biofuel production.
AB  - While research and development of algal biofuels are currently receiving much
      interest and funding, they are still not commercially viable at today's fossil
      fuel prices. However, a niche opportunity may exist where algae are grown as a by
      product of high rate algal ponds (HRAPs) operated for wastewater treatment. In
      addition to significantly better economics, algal biofuel production from
      wastewater treatment HRAPs has a much smaller environmental footprint compared to
      commercial algal production HRAPs which consume freshwater and fertilisers. In
      this paper the critical parameters that limit algal cultivation, production and
      harvest are reviewed and practical options that may enhance the net harvestable
      algal production from wastewater treatment HRAPs including CO(2) addition,
      species control, control of grazers and parasites and bioflocculation are
      discussed.

PMID- 20674342
TI  - Water hyacinth (Eichhornia crassipes) waste as an adsorbent for phosphorus
      removal from swine wastewater.
AB  - Both live plants and dried straw of water hyacinth were applied to a sequential
      treatment of swine wastewater for nitrogen and phosphorus reduction. In the
      facultative tank, the straw behaved as a kind of adsorbent toward phosphorus. Its
      phosphorus removal rate varied considerably with contact time between the straw
      and the influent. In the laboratory, the straw displayed a rapid total phosphorus
      reduction on a KH(2)PO(4) solution. The adsorption efficiency was about 36% upon
      saturation. At the same time, the water hyacinth straw in the facultative tank
      enhanced NH(3)-N removal efficiency as well. However, no adsorption was evident.
      This study demonstrated an economically feasible means to apply water hyacinth
      phosphorus straw for the swine wastewater treatment. The sequential system
      employed significantly reduced the land use, as compared to the wastewater
      stabilization pond treatment, for pollution amelioration of swine waste.

PMID- 20674343
TI  - Life-cycle assessment of microalgae culture coupled to biogas production.
AB  - Due to resource depletion and climate change, lipid-based algal biofuel has been
      pointed out as an interesting alternative because of the high productivity of
      algae per hectare and per year and its ability to recycle CO(2) from flue gas.
      Another option for taking advantage of the energy content of the microalgae is to
      directly carry out anaerobic digestion of raw algae in order to produce methane
      and recycle nutrients (N, P and K). In this study, a life-cycle assessment (LCA)
      of biogas production from the microalgae Chlorella vulgaris is performed and the
      results are compared to algal biodiesel and to first generation biodiesels. These
      results suggest that the impacts generated by the production of methane from
      microalgae are strongly correlated with the electric consumption. Progresses can
      be achieved by decreasing the mixing costs and circulation between different
      production steps, or by improving the efficiency of the anaerobic process under
      controlled conditions. This new bioenergy generating process strongly competes
      with others biofuel productions.

PMID- 20674344
TI  - Cultivation, photobioreactor design and harvesting of microalgae for biodiesel
      production: a critical review.
AB  - Microalgae have the ability to mitigate CO(2) emission and produce oil with a
      high productivity, thereby having the potential for applications in producing the
      third-generation of biofuels. The key technologies for producing microalgal
      biofuels include identification of preferable culture conditions for high oil
      productivity, development of effective and economical microalgae cultivation
      systems, as well as separation and harvesting of microalgal biomass and oil. This
      review presents recent advances in microalgal cultivation, photobioreactor
      design, and harvesting technologies with a focus on microalgal oil (mainly
      triglycerides) production. The effects of different microalgal metabolisms (i.e.,
      phototrophic, heterotrophic, mixotrophic, and photoheterotrophic growth),
      cultivation systems (emphasizing the effect of light sources), and biomass
      harvesting methods (chemical/physical methods) on microalgal biomass and oil
      production are compared and critically discussed. This review aims to provide
      useful information to help future development of efficient and commercially
      viable technology for microalgae-based biodiesel production.

PMID- 20674345
TI  - Utilization of sludge palm oil as a novel substrate for biosurfactant production.
AB  - This paper introduces sludge palm oil (SPO) as a novel substrate for
      biosurfactant production by liquid state fermentation. Potential strains of
      microorganism were isolated from various hydrocarbon-based sources at palm oil
      mill and screened for biosurfactant production with the help of drop collapse
      method and surface tension activity. Out of 22 isolates of microorganism, the
      strain S02 showed the highest bacterial growth with a surface tension of 36.2
      mN/m and was therefore, selected as a potential biosurfactant producing
      microorganism. Plackett-Burman experimental design was employed to determine the
      important nutritional requirement for biosurfactant production by the selected
      strain under controlled conditions. Six out of 11 factors of the production
      medium were found to significantly affect the biosurfactant production.
      K(2)HPO(4) had a direct proportional correlation with the biosurfactant
      production while sucrose, glucose, FeSO(4), MgSO(4), and NaNO(3) showed inversely
      proportional relationship with biosurfactant production in the selected
      experimental range.

PMID- 20674346
TI  - Application of cellulase-free xylano-pectinolytic enzymes from the same bacterial
      isolate in biobleaching of kraft pulp.
AB  - A synergistic action of xylano-pectinolytic enzymes from the same bacterial
      isolate Bacillus pumilus was evaluated for the prebleaching of kraft pulp. The
      enzymatic prebleaching of kraft pulp resulted in 8.5% reduction in kappa number
      of the pulp, showing remarkable delignification with the enzyme treatment. This
      approach resulted in 25% reduction in active chlorine consumption in subsequent
      bleaching stages without any decrease in brightness. Increase in Burst factor
      (9%), Tear factor (4.6%), Breaking length (4.4%), Double fold number (12.5%),
      Gurley porosity (4%) and Viscosity (11.8%) of enzyme treated pulp reflected the
      significant improvement in pulp properties. This is the first report describing
      the use of xylanase and pectinase produced simultaneously in the same production
      medium from the same bacterial isolate for effective biobleaching of kraft pulp.
      Use of this xylano-pectinolytic synergism in paper and pulp industry will
      ultimately help in making the process not only economically feasible but also eco
      friendly.

PMID- 20674347
TI  - Biotreatability of wastewater generated during machinery washing in a wood-based
      industry: COD, formaldehyde and nitrogen removal.
AB  - This paper describes biotreatability tests for treating a wastewater stream
      generated by wood-floor industries after cleaning and washing of machinery used
      to apply urea-formaldehyde resins onto wood-fiber boards. A biological system
      consisting of an anaerobic-intermittently aerated reactor in lab-scale was
      constructed. Since the investigated wastewater is intermittently generated, the
      system was designed to operate in batch mode. The treatment focused on removal of
      formaldehyde and COD, as well as the efficiency of nitrification-denitrification.
      The proposed cheap and relatively simple-to-operate biological system achieved
      COD and formaldehyde removal rates of 65+/-11% and 93+/-4% respectively. In spite
      of anaerobic ammonium removal and denitrification, the intermittently-aerated
      reactor showed poor performance for nitrification. Therefore, a better
      understanding of constraints for the process improvement is necessary. Regardless
      the constraints faced during the investigation, the proposed system can be
      considered feasible to partially reduce a great amount of biodegradable compounds
      in urea-formaldehyde-based wastewaters. However, to comply with strict threshold
      limits for industrial effluent discharges, the use of biological treatment
      combined with more advanced processes is needed to achieve a better quality of
      the final effluent.

PMID- 20674348
TI  - The action of bromoconduritol on ER glucosidase II.
AB  - Bromoconduritol (6-bromo-3,4,5-trihydroxycyclohex-1-ene; BCD) has been known as
      an inhibitor of glucosidase II (G-II), which plays pivotal roles in glycoprotein
      processing and folding in the ER. Previous works suggested that BCD specifically
      inhibits the cleavage of the innermost glucose (Glc) among two alpha1-3 linked
      Glc residues (cleavage-2). This study addressed the mode of BCD's inhibition
      toward G-II by using fluorescently labeled substrates. Our analysis clarified
      that BCD inhibits both cleavage-1 and cleavage-2 activities of G-II. However, the
      inhibitory activity toward cleavage-2 was 6-fold higher than that toward cleavage
      1. Inhibition against both of these activities was retained after dialysis,
      supporting that BCD exhibits inhibition through irreversible binding to G-II.

PMID- 20674349
TI  - Antimicrobial phenolic abietane diterpene from Lycopus europaeus L. (Lamiaceae).
AB  - A new acetylated highly oxygenated abietane-type diterpenoid named euroabienol
      was isolated in pure state from Lycopus europaeus L. (Lamiaceae) fruits and its
      structure elucidated through both extensive spectral and chemical means. The
      presence of a phenolic C ring with a rare substitution pattern in euroabienol and
      its high relative amount in the fruits (1%, based on the weight of the fruits)
      urged us to try to establish its possible biological role. Thus, it was screened
      for its in vitro antimicrobial activity against fifteen strains of bacteria and
      six fungal strains. Euroabienol showed a broad spectrum of activity and probably
      is a first line defense plant metabolite against pathogen attack. This is the
      first report on the occurrence of abietanes in the genus Lycopus.

PMID- 20674350
TI  - Discovery of imidazo[1,2-a]pyrazine-based Aurora kinase inhibitors.
AB  - The synthesis and structure-activity relationships (SAR) of novel, potent
      imidazo[1,2-a]pyrazine-based Aurora kinase inhibitors are described. The X-ray
      crystal structure of imidazo[1,2-a]pyrazine Aurora inhibitor 1j is disclosed.
      Compound 10i was identified as lead compound with a promising overall profile.

PMID- 20674351
TI  - Development of 2-pyrrolidinyl-N-methyl pyrimidones as potent and orally
      bioavailable HIV integrase inhibitors.
AB  - A series of 2-pyrrolidinyl-N-methyl pyrimidones HIV integrase inhibitors has been
      explored leading to the identification of derivative 13, which showed high
      activity at inhibiting viral replication in cell culture, favorable
      pharmacokinetic profile in two preclinical species, and an attractive profile
      against a panel of HIV-integrase mutants.

PMID- 20674352
TI  - Inhibition of interleukin-1beta converting enzyme (ICE or caspase 1) by aspartyl
      acyloxyalkyl ketones and aspartyl amidooxyalkyl ketones.
AB  - A series of acyloxyalkyl and amidooxyalkyl ketones appended to a carbobenzyloxy
      aspartic acid core have been prepared. The most potent of these new inhibitors
      was 4i with a K(i) of 0.5 microM. These two series provide an improved
      understanding of the binding requirements for the hydrophobic prime side of ICE.

PMID- 20674353
TI  - Development of methotrexate proline prodrug to overcome resistance by MDA-MB-231
      cells.
AB  - The resistance to methotrexate by a number of cancer cells such as breast cancer
      cell-line MDA-MB-231 due to poor permeability renders it less effective as an
      anticancer agent for these cells. Proline prodrug of methotrexate (Pro-MTX) was
      designed as a substrate of prolidase which is specific for imido bond of
      dipeptide containing proline and expected to penetrate MDA-MB-231 cells more
      efficiently. The prodrug was synthesized by solid-phase peptide synthesis method
      and examined as a substrate of pure prolidase as well as cell homogenate. The
      cytotoxicity against MDA-MB-231 and non-methotrexate resistant breast cancer cell
      line, MCF-7 was also examined by XTT assay. The results showed that Pro-MTX was a
      substrate of prolidase. It was also shown that the prodrug could be converted to
      parent drug methotrexate in Caco-2 and HeLa cell homogenate. When tested with
      Caco-2 and MCF-7 cells, Pro-MTX showed weaker cytotoxicity compared with
      methotrexate. But for methotrexate resistant MDA-MB-231 cells, Pro-MTX showed
      stronger activity than methotrexate. The results indicated that the proline
      prodrug of methotrexate may overcome the resistance of human breast cancer cells
      in culture.

PMID- 20674354
TI  - Carbonic anhydrase inhibitors. Antioxidant polyphenols effectively inhibit
      mammalian isoforms I-XV.
AB  - A series of polyphenolic derivatives, including resveratrol, dobutamine,
      curcumin, catechin and silymarine were investigated for the inhibition of all the
      catalytically active mammalian isozymes of the metalloprotein carbonic anhydrase
      (CA, EC 4.2.1.1), that is, CA I-CA XV. These polyphenols effectively inhibited
      CAs, with K(I)s in the range of 380 nM-12.02 microM. The various isozymes showed
      quite diverse inhibition profiles with these compounds, which possess scaffolds
      not present in other investigated CA inhibitors (CAIs). These data may lead to
      drug design campaigns of effective CAIs possessing a diverse inhibition mechanism
      compared to sulfonamide/sulfamate inhibitors, based on such less investigated
      scaffolds.

PMID- 20674355
TI  - Pyrrolo[1,2-a]pyrazine and pyrazolo[1,5-a]pyrazine: novel, potent, and selective
      series of Vasopressin 1b receptor antagonists.
AB  - Novel series of pyrrole-pyrazinone and pyrazole-pyrazinone have been identified
      as potent and selective Vasopressin(1b) receptor antagonists. Exploration of the
      substitution pattern around the core of these templates allowed generation of
      compounds with high inhibitory potency at the Vasopressin(1b) receptor, including
      examples that showed good selectivity with respect to Vasopressin(1a),
      Vasopressin(2), and Oxytocin receptor subtypes.

PMID- 20674356
TI  - Synthesis of selenophene derivatives as novel CHK1 inhibitors.
AB  - A series of selenophene derivatives 3 were synthesized as potential CHK1
      inhibitors. The effects of substitution on the 4'- or 5'-position of selenophene
      moiety and shifting the hydroxyl group position on C6- phenolic ring of oxindole
      were explored. This study led to the discovery of the most potent CHK1 inhibitors
      29-33 and 39-43, which had IC(50) values in the subnanomolar range.

PMID- 20674357
TI  - Novel imidazobenzazepine derivatives as dual H1/5-HT2A antagonists for the
      treatment of sleep disorders.
AB  - A novel imidazobenzazepine template (5a) with potent dual H(1)/5-HT(2A)
      antagonist activity was identified. Application of a zwitterionic approach to
      this poorly selective and poorly developable starting point successfully
      delivered a class of high quality leads, 3-[4-(3-R(1)-2-R-5H-imidazo[1,2
      b][2]benzazepin-11-yl)-1-piperazinyl]-2,2-dimethylpropanoic acids (e.g., 9, 19,
      20, and 21), characterized by potent and balanced H(1)/5-HT(2A) receptor
      antagonist activities and good developability profiles.

PMID- 20674358
TI  - Studies on the structure-activity relationship of 1,3,3,4-tetra-substituted
      pyrrolidine embodied CCR5 receptor antagonists. Part 2: Discovery of highly
      potent anti-HIV agents.
AB  - Modification of 1,3,3,4-tetra-substituted pyrrolidine embodied CCR5 receptor
      antagonists revealed that introducing a fluoro group at the 3-position of the 3
      phenyl group to reduce metabolism did not adversely affect the high potency
      against HIV infection, and that replacing the piperidine ring with a tropane ring
      could deliver the most potent anti-HIV agents. Stereochemistry of the substituted
      tropane ring is essential for maintaining the potent anti-HIV activity because
      only exo-isomers displayed subnanomolar whole cell activity.

PMID- 20674359
TI  - Seeing mutations in living cells.
AB  - BACKGROUND: Evolution depends on mutations: rare errors in the transmission of
      genetic information. Experimentally, mutations have been found by detecting
      altered phenotypes or sequencing complete genomes, but most mutations do not have
      overt phenotypes, and sequencing is expensive and has limited time resolution.
      The major source of mutations is DNA replication errors. Nearly all mistakes in
      DNA replication are detected and repaired by the mismatch repair machinery.
      RESULTS: We use a functional, fluorescently labeled derivative of one of the key
      mismatch repair proteins (MutL) to see and count the small fraction of errors in
      Escherichia coli that does not get repaired and is converted into stable
      mutations by the next round of DNA replication. Over a 300-fold range, there is a
      linear relationship between the frequency of fluorescent foci and the genetically
      measured mutation frequency, and the mean frequency of fluorescent foci agrees
      well with estimates of the global mutation rate. CONCLUSION: We describe a method
      for detecting the majority of genomic mutations emerging in living cells,
      independently of their potential phenotype. The distribution of emerging
      mutations per cell is roughly Poisson distributed, suggesting that all the cells
      in the population have roughly the same mutation rate.

PMID- 20674360
TI  - Experience-driven plasticity in binocular vision.
AB  - Experience-driven neuronal plasticity allows the brain to adapt its functional
      connectivity to recent sensory input. Here we use binocular rivalry, an
      experimental paradigm in which conflicting images are presented to the individual
      eyes, to demonstrate plasticity in the neuronal mechanisms that convert visual
      information from two separated retinas into single perceptual experiences.
      Perception during binocular rivalry tended to initially consist of alternations
      between exclusive representations of monocularly defined images, but upon
      prolonged exposure, mixture percepts became more prevalent. The completeness of
      suppression, reflected in the incidence of mixture percepts, plausibly reflects
      the strength of inhibition that likely plays a role in binocular rivalry.
      Recovery of exclusivity was possible but required highly specific binocular
      stimulation. Documenting the prerequisites for these observed changes in
      perceptual exclusivity, our experiments suggest experience-driven plasticity at
      interocular inhibitory synapses, driven by the correlated activity (and also the
      lack thereof) of neurons representing the conflicting stimuli. This form of
      plasticity is consistent with a previously proposed but largely untested anti
      Hebbian learning mechanism for inhibitory synapses in vision. Our results
      implicate experience-driven plasticity as one governing principle in the neuronal
      organization of binocular vision.

PMID- 20674361
TI  - The yolk syncytial layer in early zebrafish development.
AB  - The yolk syncytial layer (YSL) plays crucial roles in early zebrafish
      development. The YSL is a transient extra-embryonic syncytial tissue that forms
      during early cleavage stages and persists until larval stages. During
      gastrulation, the YSL undergoes highly dynamic movements, which are tightly
      coordinated with the movements of the overlying germ layer progenitor cells, and
      has critical functions in cell fate specification and morphogenesis of the early
      germ layers. Movement coordination between the YSL and blastoderm cells is
      dependent on contact between these tissues, and is probably required for the
      patterning and morphogenetic function of the YSL. In this review, we will discuss
      recent advances in elucidating the molecular and cellular mechanisms underlying
      the YSL morphogenesis and movement coordination between the YSL and blastoderm
      during early development.

PMID- 20674362
TI  - Family members' lived experience in the intensive care unit: a phemenological
      study.
AB  - AIM: To describe the lived experience of family members of patients in the
      intensive care unit. BACKGROUND: Admission of a critically ill relative to an
      intensive care unit causes anxiety and stress to family members. Nursing care is
      initially focused on maintaining the physiological stability of the patient and
      less on the needs and concerns of family members. Understanding how families make
      sense of this experience may help nurses focus on the delivery of family centred
      care. METHODOLOGY: A phenomenological method was used to describe the lived
      experiences of family members of patients in an intensive care unit. In-depth
      interviews were conducted with six family members and analysed using qualitative
      thematic analysis. RESULTS: Four main themes emerged from the data: the need to
      know, making sense of it all, being there with them and caring and support.
      Family members needed honest information about the patient's progress and outcome
      to make the situation more bearable for them. Making sense of the situation was a
      continuous process which involved tracking and evaluating care given. Being with
      their relative sustained their family bond and was a way to demonstrate love and
      support. Caring reassurance provided by the nurses enabled a sense of security.
      Support was needed by family members to assist them in coping. CONCLUSION: The
      research provided an insight into how family members viewed the impact of the
      admission and how they subsequently found ways of dealing with the situation.
      RELEVANCE TO CLINICAL PRACTICE: Using a holistic approach to nursing assessment
      and care delivery in intensive care necessitates that nurses interact with and
      care for family members of patients. Development of a philosophy of family
      centred care is necessary, with formal assessment of families to take place soon
      after admission and an appropriate plan of care drawn up at this time.

PMID- 20674363
TI  - Staff empowerment in intensive care: nurses' and physicians' lived experiences.
AB  - AIM: The purpose of the study was to describe empowerment from the perspective of
      intensive care staff. What makes intensive care staff experience inner strength
      and power? BACKGROUND: Intensive care staff are repeatedly exposed to traumatic
      situations and demanding events, which could result in stress and burnout
      symptoms. A higher level of psychological empowerment at the workplace is
      associated with increased work satisfaction and mental health, fewer burnout
      symptoms and a decreased number of sick leave days. METHOD: Open-ended interviews
      were conducted with 12 intensive care unit (ICU) staff (four registered nurses,
      four enrolled nurses and four physicians) in southern Sweden. Data were analysed
      using a phenomenological method. FINDINGS: Intensive care staff were found to be
      empowered both by internal processes such as feelings of doing good, increased
      self-esteem/self-confidence and increased knowledge and skills, and by external
      processes such as nourishing meetings, well functioning teamwork and a good
      atmosphere. CONCLUSION: Findings show that not only personal knowledge and
      skills, but also a supporting atmosphere and a good teamwork, has to be focused
      and encouraged by supervisors in order to increase staff's experiences of
      empowerment. Staff also need a chance to feel that they do something good for
      patients, next of kin and other staff members.

PMID- 20674364
TI  - Non-paretic lower limb constraint with a step decreases the asymmetry of vertical
      forces during sit-to-stand at two seat heights in subjects with hemiparesis.
AB  - This study investigated the effects of non-paretic leg constraint by a step,
      combined with two different seat heights, on weight-bearing on the paretic leg
      and reduction of asymmetry during STS. Thirteen adult subjects (60.4 +/- 5.7
      years) were selected, with chronic hemiparesis (43.7 +/- 50 months) due to
      stroke. Two force plates were used to analyze the vertical force (Fz) in the
      standing position and during STS. Individuals were instructed to rise from an
      instrumented bench at two seat heights, 100% (normal) and 130% (elevated) of knee
      height with four foot positions: (1) spontaneous (SPO); (2) symmetrical (SYM);
      (3) asymmetrical (ASY; non-paretic limb in front of paretic); and (4) step (STP;
      non-paretic limb supported on a step and paretic at ground level). A reduction of
      asymmetry occurred during STS movement when the non-paretic leg was constrained
      by a step compared with positions SPO (p<0.001), SYM (p<0.001) and ASY (p=0.02)
      at the normal seat level. Raising seat height to 130% increased asymmetry in the
      SPO condition (p=0.01); however, this effect was reversed in the ASY and STP
      conditions. Constraint of the non-paretic leg by a step is presented as a
      potential therapeutic route to a less asymmetrical STS. Together with a higher
      seat level this can benefit the training of individuals with hemiparesis unable
      to keep the paretic foot backward during STS from a standard seat height.

PMID- 20674365
TI  - Nanostructured bacterial materials for innovative medicines.
AB  - The development of innovative medicines and personalized biomedical approaches
      require the identification and implementation of new biocompatible materials
      produced by methodologically simple and cheap fabrication methods. The biological
      fabrication of materials, mostly carried out by microorganisms, has historically
      provided organic compounds with wide-spectrum biomedical applications, including
      hyaluronic acid, poly(gamma-glutamic acid) and polyhydroxyalkanoates.
      Additionally, the implementation of new methodological platforms such as
      metabolic engineering and systems biology have facilitated the controlled
      production of natural nanoparticles produced by bacteria, including metallic
      deposits of Au, Ag, Cd, Zn or Fe, virus-like particles or other nanoscale protein
      only entities. The unexpected potential of such self-organized and functional
      materials in nanomedical scenarios (especially in drug delivery, imaging and
      tissue engineering) prompts serious consideration of further exploitation of
      bacterial cell factories as convenient alternatives to chemical synthesis and as
      sources of novel bioproducts that could dramatically expand the existing catalog
      of biomedical materials.

PMID- 20674366
TI  - Nitrogen fixation and nitrogen transformations in marine symbioses.
AB  - Many marine organisms have coevolved symbiotic relationships with nitrogen-fixing
      bacteria in nitrogen limited environments such as coral reefs. In addition, some
      of these organisms also harbor microbes that carry out nitrification and
      denitrification. Prokaryotes involved in nitrogen fixation and other nitrogen
      transformations are symbionts in a range of eukaryotic hosts in the marine
      environment including shipworms, diatoms, corals and sponges. Molecular genetic
      approaches, and other analytical techniques, have provided exciting new insights
      into symbiont diversity and the relationship between host and symbiont. We review
      the current state of knowledge of these symbioses and highlight important avenues
      for future studies.

PMID- 20674367
TI  - Design, synthesis, and evaluation of quinazoline T cell proliferation inhibitors.
AB  - We report here on a class of quinazoline molecules that inhibit T cell
      proliferation. The most potent compound N-p-tolyl-2-(3,4,5
      trimethoxyphenyl)quinazolin-4-amine (S101) and its close analogs were found to
      inhibit the proliferation of T cells from human peripheral blood mononuclear
      cells (PBMC) and Jurkat cells, with IC(50) in the sub-micromolar range. The
      inhibitor induced G2 cell cycle arrest but did not inhibit IL-2 secretion. The
      anti-proliferative effect correlated with inhibition of the tyrosine
      phosphorylation of SLP-76, a molecular element in the signaling pathway of the T
      cell receptor (TCR). The inhibitor restrained proliferation of lymphocytes with
      much higher potency than non-hematopoietic cells. This new class of specific T
      cell proliferation inhibitors may serve as lead molecules for the development of
      agents aimed at diseases in which T cell signaling plays a role and agents to
      induce tolerance to grafted tissues or organs.

PMID- 20674368
TI  - New effective inhibitors of the Abelson kinase.
AB  - The effects of substituents on the aryl ring were studied by the preparation and
      testing of several PD173955 analogs. Inserting a single carbon atom into the C-N
      bond in the aniline subunit (PDC) reduced the kinase inhibition by a factor of
      200. Despite its decreased affinity for Abl compared with PD173955, PDC exhibits
      a Ki very similar to that reported for Imatinib. Increased water solubility is
      also gained by replacing the thiomethyl group with an amino or glycyl moiety. For
      both PD173955 and PDC, the analogs with amino groups in place of the methylthio
      group are 10 times more inhibitory than the parent molecules. Two molecules were
      identified with Kis about three orders of magnitude lower than reported for
      Imatinib.

PMID- 20674369
TI  - Glycopeptide dendrimer colchicine conjugates targeting cancer cells.
AB  - Screening of a 65,536-member one-bead-one-compound (OBOC) combinatorial library
      of glycopeptide dendrimers of structure
      ((betaGal)(n)(+1)X(8)X(7)X(6)X(5))(2)DapX(4)X(3)X(2)X(1)(beta-Gal)(m)
      (betaGal=beta-galactosyl-thiopropionic acid, X(8-1)=variable amino acids, Dap=l
      2,3-diaminopropionic acid, n, m=0, or 1 if X(8)=Lys resp. X(1)=Lys) for binding
      of Jurkat cells to the library beads in cell culture, resynthesis and testing
      lead to the identification of dendrimer J1 (betaGal-Gly-Arg-His-Ala)(2)Dap-Thr
      Arg-His-Asp-CysNH(2) and related analogues as delivery vehicles. Cell targeting
      is evidenced by FACS with fluorescein conjugates such as J1F. The colchicine
      conjugate J1C is cytotoxic with LD(50)=1.5 microM. The beta-galactoside groups
      are necessary for activity, as evidenced by the absence of cell-binding and
      cytotoxicity in the non-galactosylated, acetylated analogue AcJ1F and AcJ1C,
      respectively. The pentagalactosylated dendrimer J4 betaGal(4)(Lys-Arg-His
      Leu)(2)Dap-Thr-Tyr-His-Lys(betaGal)-Cys) selectively labels Jurkat cell as the
      fluorescein derivative J4F, but its colchicine conjugate J4C lacks cytotoxicity.
      Tubulin binding assays show that the colchicine dendrimer conjugates do not bind
      to tubulin, implying intracellular degradation of the dendrimers releasing the
      active drug.

PMID- 20674370
TI  - Synthesis and properties of triplex-forming oligonucleotides containing 2'-O-(2
      methoxyethyl)-5-(3-aminoprop-1-ynyl)-uridine.
AB  - 2'-O-(2-Methoxyethyl)-5-(3-aminoprop-1-ynyl)-uridine phosphoramidite (MEPU) has
      been synthesized from d-ribose and 5-iodouracil and incorporated into triplex
      forming oligonucleotides (TFOs) by automated solid-phase oligonucleotide
      synthesis. The TFOs gave very high triplex stability with their target duplexes
      as measured by ultraviolet/fluorescence melting and DNase I footprinting. The
      incorporation of MEPU into TFOs renders them resistant to degradation by serum
      nucleases.

PMID- 20674371
TI  - Novel nucleosides as potent influenza viral inhibitors.
AB  - Influenza virus infection constitutes a significant health problem in need of
      more effective therapies. We have recently identified ((2R,3S,4R,5R)-3-acetoxy-5
      (4-benzamido-2-oxopyrimidin-1(2H)-yl)-4-fluoro-3,4-dimethyl-tetrahydrofuran-2-yl)
      methyl benzoate (18c) as a potent influenza virus inhibitor. We now here report
      the synthesis and evaluation of a series of C-3' modified ribose nucleosides.
      These novel compounds were prepared, primarily by taking known ((2R,3R,4R)-3
      benzoyloxy-4-fluoro-4-methyl-5-oxo-tetrahydrofuran-2-yl)methyl benzoate (1) and
      converting it in to C-3 keto sugar (7), reacting C-3 keto group with methyl
      magnesium bromide, followed by coupling these sugars with purine and pyrimidine
      bases. Anti influenza viral activity was determined by screening against both A
      and B viral strains.

PMID- 20674372
TI  - Rational design, synthesis, and characterization of highly fluorescent optical
      switches for high-contrast optical lock-in detection (OLID) imaging microscopy in
      living cells.
AB  - A major challenge in cell biology is to elucidate molecular mechanisms that
      underlie the spatio-temporal control of cellular processes. These studies require
      microscope imaging techniques and associated optical probes that provide high
      contrast and high-resolution images of specific proteins and their complexes.
      Auto-fluorescence however, can severely compromise image contrast and represents
      a fundamental limitation for imaging proteins within living cells. We have
      previously shown that optical switch probes and optical lock-in detection (OLID)
      image microscopy improve image contrast in high background environments. Here, we
      present the design, synthesis, and characterization of amino-reactive and cell
      permeable optical switches that integrate the highly fluorescent fluorophore,
      tetramethylrhodamine (TMR) and spironaphthoxazine (NISO), a highly efficient
      optical switch. The NISO moiety in TMR-NISO undergoes rapid and reversible,
      excited-state driven transitions between a colorless spiro (SP)-state and a
      colored merocyanine (MC)-state in response to irradiation with 365 and >530nm
      light. In the MC-state, the TMR (donor) emission is almost completely
      extinguished by Forster resonance energy transfer (FRET) to the MC probe
      (acceptor), whereas in the colorless SP-state, the quantum yield for TMR
      fluorescence is maximal. Irradiation of TMR-NISO with a defined sequence of 365
      and 546nm manipulates the levels of SP and MC with concomitant modulation of FRET
      efficiency and the TMR fluorescence signal. High fidelity optical switching of
      TMR fluorescence is shown for TMR-NISO probes in vitro and for membrane permeable
      TMR-NISO within living cells.

PMID- 20674373
TI  - Design, synthesis, and pharmacological effects of structurally simple ligands for
      MT(1) and MT(2) melatonin receptors.
AB  - A series of phenoxyalkyl and phenylthioalkyl amides were prepared as
      melatoninergic ligands. Modulation of affinity of the newly synthesized compound
      by applying SARs around the terminal amide moiety, the alkyl chain, and the
      methoxy group on the aromatic ring provides compounds with nanomolar affinity for
      both melatonin receptor subtypes. Affinity towards MT(1) and MT(2) receptors were
      modulated also exploiting chirality. The investigation of intrinsic activity
      revealed that all the tested compounds behave as full or partial agonists.

PMID- 20674374
TI  - New synthetic flavone derivatives induce apoptosis of hepatocarcinoma cells.
AB  - Natural flavonoids have broad biological activity, including anticancer. In this
      study, a series of novel flavone derivatives were synthesized with the
      substitutions of chlorine, isopropyl, methoxy, and nitro groups on the benzene
      ring of flavone skeleton to develop effective anticancer agents.
      Antiproliferative assays showed that the synthesized chemicals possess notable
      activity against hepatocarcinoma cells (HepG-2); in particular, the compound 6f
      with chlorine and dimethoxy modifications at the two benzene rings showed an
      IC(50) at 1.1 microM to HepG-2. The 6f also displayed marked anticancer activity
      towards a panel of cancer cells, including nasopharyngeal carcinoma cells (CNE-2
      and CNE-1), breast adenocarcinoma cell (MCF-7), and epithelial carcinoma cells
      (Hela). Exposing HepG-2 cells to compound 6f at 10 microM induced chromatin
      condensation, nuclear disassembly, and DNA fragmentation. In 6f-treated HepG-2
      cells, the sub-G(0) population was remarkably increased; and in these cells, both
      caspase-8 and caspase-9 activity was significantly increased, which in turn
      activated caspase-3. In addition, proapoptotic Bax was upregulated by compound 6f
      while the antiapoptotic Bcl-2 was downregulated. Taken together, our data suggest
      that the new flavonoid derivative 6f triggers apoptosis through both death
      receptor and mitochondria-dependent intrinsic pathways, being a potent
      therapeutic agent against hepatocarcinoma.

PMID- 20674375
TI  - Design, synthesis, and in vitro antiprotozoal, antimycobacterial activities of N
      {2-[(7-chloroquinolin-4-yl)amino]ethyl}ureas.
AB  - We have synthesized a new series of quinoline tripartite hybrids from
      chloroquine, ethambutol, and isoxyl drugs, using a short synthetic route.
      Compounds 1-8 were tested in vitro against five protozoa (Giardia intestinalis,
      Trichomonas vaginalis,Entamoeba histolytica, Leishmania mexicana and Trypanosoma
      cruzi) and Mycobacterium tuberculosis. N-(4-Butoxyphenyl)-N'-{2-[(7
      chloroquinolin-4-yl)amino]ethyl}urea (6) was the most active compound against all
      parasites tested. Compound 6 was 670 times more active than metronidazole,
      against G. intestinalis. It was as active as pentamidine against L. mexicana, and
      it was twofold more potent than ethambutol and isoxyl versus M. tuberculosis.
      This compound could be considered as a new broad spectrum antimicrobial agent.

PMID- 20674376
TI  - C2C12 myoblast sensitivity to different apoptotic chemical triggers.
AB  - Apoptosis is a form of cell death crucial for normal development and tissue
      homeostasis. Its typical features include chromatin changes, nuclear breakdown,
      plasma membrane blebbing and splitting of cellular content into apoptotic bodies,
      that progressively undergo phagocytosis. Apoptosis is considered essential for
      skeletal muscle development, where defective cells are deleted during
      differentiation. In addition, it plays a relevant role in several muscle
      myopathies, as well as in denervation and disuse. The aim of this study was to
      evaluate muscle cell sensitivity to different apoptotic triggers, acting through
      different mechanisms of action. Chemical agents, active against distinct
      intracellular targets, such as mitochondrial respiratory chain and DNA, have been
      chosen to better highlight cell death mechanisms. To induce apoptosis, C2C12
      myoblasts have been exposed to H(2)O(2), staurosporine, cisplatin and etoposide,
      at different doses and incubation times, and they have been analysed by flow
      cytometry, scanning and transmission electron microscopy. Flow cytometry analysis
      revealed a certain subdiploid peak after all treatments. The best apoptotic
      effect was observable, as confirmed at reverted microscope, at minimum doses and
      after the major exposure time. At ultrastructural level programmed cell death has
      been observed. Characteristic chromatin condensation and margination, as well as
      apoptotic bodies, frequently appeared, even if in the presence of secondary
      necrosis; surface blebs were also observed during scanning microscopic
      observation. In particular, exposure to H(2)O(2) or staurosporine showed the
      largest number of myoblasts in late apoptotic stages and in secondary necrosis.
      Cisplatin treatments revealed few early apoptotic cells. The analysis of
      etoposide-induced apoptosis was in agreement with data obtained from flow
      cytometry, indicating a significant increase of apoptotic cell number. These
      results suggest that all conditions are able to induce apoptosis in C2C12
      myoblasts, which occurs, considering trigger mechanisms of action, mostly
      following the mitochondrial pathway, if not excluding that due to DNA damage.
      Therefore, mitochondria permeability alteration is an important step in skeletal
      muscle programmed cell death. This last conclusion seems to have a significant
      relevance in understanding the mechanisms involved in muscle disorders,
      denervation and chronic muscle disuse, conditions frequently characterized by a
      decline in mitochondrial content and by an increase of mitochondrial apoptosis
      susceptibility.

PMID- 20674377
TI  - Quantitative expression of myogenic regulatory factors MyoD and myogenin in pacu
      (Piaractus mesopotamicus) skeletal muscle during growth.
AB  - Skeletal muscle growth is regulated by differential expression of myogenic
      regulatory factors (MRFs). We evaluated hyperplasia, hypertrophy and quantitative
      expression of MRFs MyoD and myogenin in 45, 90, 180, and 400 days post-hatching
      (dph) and adult pacu (Piaractus mesopotamicus) skeletal muscle. Transverse
      sections of white dorsal muscles were obtained to evaluate hypertrophy and
      hyperplasia. MyoD and myogenin gene expression was determined by reverse
      transcription quantitative real-time polymerase chain reaction (RT-qPCR). Pacu
      skeletal muscle had similar morphology at all stages. The highest and the lowest
      frequencies of fiber diameters <20 MUm were found at the 45 dph and adult stages,
      respectively. Their frequency was similar in the 90, 180, and 400 dph stages. The
      highest percentage of >50 MUm diameter fibers were found in 180 and 400 dph, and
      adult fish. Hyperplasia was the main mechanism observed in pacu skeletal muscle
      growth at 45dph; this declined through 90, 180, and 400 dph and remained low in
      adult fish; the latter presented hypertrophy as the main mechanism responsible
      for skeletal muscle growth. The high frequencies of 20-50 MUm diameter fibers at
      90, 180, and 400 dph can be related to intense hypertrophy. The mRNA levels for
      MyoD and myogenin were similar in 45, 90, and 400 dph and adult fish, peaking at
      180 dph. The high MyoD expression at 180 dph can be related to intense myoblast
      proliferation and hyperplasia, while high myogenin expression can be related to
      intense myoblast differentiation and fusion during hypertrophy. MyoD and myogenin
      expression patterns in adults can respectively be associated with myoblast
      proliferation and differentiation, which both contribute to hypertrophy.
      Differential MyoD and myogenin expression in pacu white muscle probably is
      associated with differences in growth patterns during the stages analyzed. In
      this study, the 180 dph pacu could represent an interesting phase to investigate
      suitable strategies in commercial fish production focusing on skeletal muscle
      growth improvement to raise healthy, fast-growing fish.

PMID- 20674378
TI  - The optimization of an energy-dispersive X-ray diffraction system for potential
      clinical application.
AB  - In the past decade, energy-dispersive X-ray diffraction (EDXRD) has been used to
      identify the nature of tissues. However, these systems have limited clinical use
      because of problems such as the long measurement times. In this study, the
      relation between various setup parameters and some performance specifications
      such as sensitivity, spatial resolution and momentum transfer resolution were
      assessed using both geometrical calculations and modeling. Accuracy of the
      derived relations was also confirmed by means of experimental measurements. As an
      example, the optimum parameters were determined for obtaining diffraction
      patterns of breast tissue for an efficient acquisition time. Accordingly, the
      results of this study could introduce a useful tool for EDXRD optimization in
      clinical application.

PMID- 20674379
TI  - Effects of omentopexy combined with granulocyte colony-stimulating factor in a
      rabbit heart model.
AB  - OBJECTIVE: We investigated whether omentopexy combined with subcutaneously
      administered granulocyte colony-stimulating factor (G-CSF) reduces infarction
      areas and improves left ventricular dysfunction in a rabbit model of coronary
      occlusion and reperfusion. METHODS: A coronary artery of a male Japanese white
      rabbit was ligated for 30 min and then reperfused. An omental pedicle graft was
      fixed onto the myocardial ischemic area after abrading the epicardium. G-CSF (10
      MUg kg(-1)day(-1)) was subcutaneously administered for 5 days postoperatively.
      Animals were assigned to groups (n = 7 per group) as follows: group N, saline;
      group O, omentopexy and saline; group G, G-CSF; and group OG, omentopexy and G
      CSF. At 4 weeks postoperatively, left ventricular ejection fraction and left
      ventricular end-diastolic diameter were evaluated by echocardiography. Harvested
      left ventricles were stained with Evans blue and triphenyltetrazolium chloride to
      measure necrotic and fibrotic areas. The arteriolar density in ischemic and
      nonischemic areas was evaluated. At 7 days postoperatively, the intrathoracic
      omentum was evaluated (n = 6 per group). RESULTS: Echocardiography at 4 weeks
      postoperatively revealed significant improvement in the left ventricular
      dysfunction of group OG. Necrosis and fibrosis in ischemic areas were
      significantly reduced in groups G and OG. Arteriolar density in the ischemic area
      and intrathoracic omentum weight were increased largely in group OG than in the
      other groups. CONCLUSIONS: Omentopexy with G-CSF offers more potential benefits
      for the ischemic heart than G-CSF alone.

PMID- 20674380
TI  - A coronary artery stent--in the radial artery!

PMID- 20674381
TI  - Editorial comment: Outcomes and re-interventions after one-stage repair of
      transposition of the great arteries and aortic arch obstruction.

PMID- 20674383
TI  - Pore size is significant in hemofiltration.

PMID- 20674384
TI  - Left atrial ablation through monolateral thoracotomy.

PMID- 20674385
TI  - Epithelial ovarian cancer: focus on targeted therapy.
AB  - Ovarian cancer remains the leading cause of gynecological cancer-related
      mortality in the Western World despite the advances in surgical techniques and
      chemotherapy regimens over the past three decades. Although response rates and
      complete responses in advanced disease are >80% and 40-60%, respectively, after
      first-line treatment with carboplatin and paclitaxel, most of the patients will
      eventually relapse with a median progression-free survival of 18 months.
      Currently, research efforts have improved our understanding on the molecular
      biology of ovarian cancer and novel targeted treatment strategies are likely to
      contribute to the management of the disease and give the chance to an
      individualized therapeutic approach.

PMID- 20674386
TI  - ERR receptors as potential targets in osteoporosis.
AB  - The bone fragility and increased fracture risk associated with osteoporosis in
      post-menopausal women is a major public health concern. Current treatments for
      osteoporosis relying on hormone replacement therapies are suspected to have an
      association with increased breast cancer risk, highlighting the need for
      identifying new potential targets in bone. Recent data suggest that the estrogen
      related receptor (ERR)alpha, an orphan nuclear receptor, represses osteoblast
      differentiation, and that its deletion in knockout mouse models results in
      increased mineral density. Furthermore, modulation of ERRalpha activity reduces
      proliferation and tumorigenesis of breast cancer cells. These results indicated
      that inhibition of ERRalpha might provide a treatment for osteoporosis without
      displaying adverse effects in breast cancer. This review focuses on the role of
      the ERR receptors, and in particular ERRalpha, in the differentiation of bone
      precursor cells and its consequences on bone homeostasis, and discusses the
      possible grounds for the discrepancies reported in the literature.

PMID- 20674387
TI  - Retinoid X receptors: common heterodimerization partners with distinct functions.
AB  - Retinoid X receptors (RXRs) have been implicated in a diversity of cellular
      processes ranging from cellular proliferation to lipid metabolism. These
      pleiotropic effects stem not only from the ability of RXRs to dimerize with
      diverse nuclear receptors, which exert transcriptional control on specific
      aspects of cell biology, but also because binding of RXR ligands to heterodimers
      can stimulate transcriptional activation by RXR partner receptors. This signaling
      network is rendered more complex by the existence of different RXR isotypes
      (RXRalpha, RXRbeta, RXRgamma) with distinct properties that thereby modulate the
      transcriptional activity of RXR-containing heterodimers. This review discusses
      the emerging roles of RXR isotypes in the RXR signaling network and possible
      implications for our understanding of nuclear receptor biology and pharmacology.

PMID- 20674388
TI  - Expression, refolding and purification of a human interleukin-17A variant.
AB  - A human interleukin-17A (IL-17A) variant was overexpressed in Escherichia coli
      BL21 (DE3) under the control of a T(7) promoter. The resulting insoluble
      inclusion bodies were isolated and solubilized by homogenization with 6 M
      guanidine HCl. The denatured recombinant human IL-17A variant was refolded in 20
      mM Tris-HCl, pH 9.0, 500 mM arginine, 500 mM guanidine HCl, 15% glycerol, 1 mM
      cystamine, and 5 mM cysteine at 2-8 degrees C for 40 h. The refolded IL-17A
      variant was subsequently purified using a combination of cation-exchange,
      reversed-phase and fluoroapatite chromatography. The final purified product was a
      monodisperse and crystallizable homodimer with a molecular weight of 30,348.3 Da.
      The protein was active in both receptor binding competition assay and IL-17A
      dependent biological activity assay using human dermal fibroblasts.

PMID- 20674389
TI  - An efficient data format for mass spectrometry-based proteomics.
AB  - The diverse range of mass spectrometry (MS) instrumentation along with
      corresponding proprietary and nonproprietary data formats has generated a
      proteomics community driven call for a standardized format to facilitate
      management, processing, storing, visualization, and exchange of both experimental
      and processed data. To date, significant efforts have been extended towards
      standardizing XML-based formats for mass spectrometry data representation,
      despite the recognized inefficiencies associated with storing large numeric
      datasets in XML. The proteomics community has periodically entertained alternate
      strategies for data exchange, e.g., using a common application programming
      interface or a database-derived format. However, these efforts have yet to gain
      significant attention, mostly because they have not demonstrated significant
      performance benefits over existing standards, but also due to issues such as
      extensibility to multidimensional separation systems, robustness of operation,
      and incomplete or mismatched vocabulary. Here, we describe a format based on
      standard database principles that offers multiple benefits over existing formats
      in terms of storage size, ease of processing, data retrieval times, and
      extensibility to accommodate multidimensional separation systems.

PMID- 20674390
TI  - Changes in muscle activation patterns and subjective low back pain ratings during
      prolonged standing in response to an exercise intervention.
AB  - BACKGROUND: Low back pain (LBP) development has been associated with occupational
      standing. Increased hip and trunk muscle co-activation is considered to be
      predisposing for LBP development during standing in previously asymptomatic
      individuals. The purpose of this work was to investigate muscle activation and
      LBP responses to a prescribed exercise program. Pain-developing (PD) individuals
      were expected to have decreased LBP and muscle co-activation following exercise
      intervention. METHODS: Electromyography (EMG) data were recorded from trunk and
      hip muscle groups during 2-h of standing. An increase of >10mm on visual analog
      scale (VAS) during standing was threshold for PD categorization. Participants
      were assigned to progressive exercise program with weekly supervision or control
      (usual activity) for 4 weeks then re-tested. RESULTS: Forty percent were
      categorized as PD on day 1, VAS=24.2 (+/-4.0)mm. PD exercisers (PDEX) had lower
      VAS scores (8.93+/-3.66 mm) than PD control (PDCON) (16.5+/-6.3 mm) on day 2
      (p=0.007). Male PDEX had decreased gluteus medius co-activation levels (p<0.05)
      on day 2. DISCUSSION: The exercise program proved beneficial in reducing LBP
      during standing. There were changes in muscle activation patterns previously
      associated with LBP. Predisposing factors for LBP during standing were shown to
      change positively with appropriate exercise intervention.

PMID- 20674391
TI  - Internalization of a second transhepatic biliary access with a captured microwire
      forced-buckle maneuver: description, anatomic applications, and results.
AB  - Percutaneous biliary drains are classified into external and internal/external
      drains. Internal/external drains can drain bile externally and internally (ie,
      anatomically) into bowel. Internal drainage is usually desired because it is
      associated with less morbidity. Not infrequently, operators encounter a situation
      in which one of two transhepatic biliary access tracts has been successfully
      internalized, and a second access cannot be internalized. The present report
      describes a technique that internalizes a second percutaneous transhepatic
      biliary access-relying on an initially successful first internalization-by
      capturing a microwire from the externalized to the internalized tract and forcing
      it down into the bowel. The anatomic applications and results of this technique
      are described.

PMID- 20674392
TI  - Comparison of the endotracheal cardiac output monitor to thermodilution in
      cardiac surgery patients.
AB  - OBJECTIVES: To compare cardiac output (CO) measurements from a novel endotracheal
      bioimpedance cardiac output monitor device (ECOM; ConMed, Irvine, CA) to
      simultaneous pulmonary artery thermodilution (TD) CO. DESIGN: Prospective study.
      SETTING: One academic hospital. PARTICIPANTS: Forty volunteer patients undergoing
      cardiac surgery. INTERVENTIONS: Intraoperative CO measurements. MEASUREMENTS AND
      MAIN RESULTS: Simultaneous comparative data points were collected from ECOM and
      TD at 4 periods: post-induction, post-sternotomy, post-cardiopulmonary bypass,
      and post-chest closure. The mean CO(TD) was compared with CO(ECOM) for each
      operative period then assessed for agreement by linear regression, Bland-Altman
      analysis, and percent error methods. There were 35 men (87.5%) with a mean age of
      66 +/- 10.7 years in the present study population. R values (p value) for the 4
      time periods were 0.50 (0.002), 0.33 (0.035), 0.42 (0.007), and 0.48 (0.002).
      Bias and 95% limits of agreement in L/min were -0.11 (-2.40 to 2.18), 0.04 (-2.57
      to 2.65), -0.06 (-2.86 to 2.74), and 0.02 (-2.42 to 2.45). Percent errors of the
      4 time periods were 51%, 53%, 50%, and 48%. CONCLUSIONS: ECOM did not adequately
      agree with TD in patients undergoing cardiac surgery.

PMID- 20674393
TI  - Endotracheal cardiac output monitor in a patient with severe tricuspid
      regurgitation.

PMID- 20674394
TI  - Transfusion requirements in 811 patients during and after cardiac surgery: a
      prospective observational study.
AB  - OBJECTIVE: To identify patients at risk for intra- and postoperative blood
      product transfusion in a mixed adult cardiac surgical patient population. DESIGN:
      A prospective, observational study. SETTING: A single-center university hospital.
      PARTICIPANTS: Patients (n = 811) undergoing cardiac surgery from January 1, 2008,
      to November 30, 2008. INTERVENTIONS: The outcome in terms of transfusion of red
      blood cells (RBCs), fresh frozen plasma (FFP), and/or pooled platelets within the
      first 24 hours after surgery was studied. Pre- and perioperative risk factors for
      bleeding and transfusion of blood products were studied. MEASUREMENTS AND MAIN
      RESULTS: The majority of RBCs and FFP (>70%) were given to a minority of patients
      (<12%). The type of surgical procedure, previous cardiac surgery, and emergency
      operations were all significantly associated with the transfusion of RBCs, FFP,
      and platelets. Antithrombotic therapy was not significantly associated with the
      transfusion requirement in the mixed group of cardiac patients. However, in the
      low-risk procedures such as coronary artery bypass graft surgery, ongoing
      antithrombotic therapy at the time of the operation significantly increased the
      risk of transfusion in this otherwise low-risk category of surgery. CONCLUSIONS:
      The identification of high-risk patients is necessary to optimize the
      perioperative management of bleeding complications. Because of the high
      variability in transfusion requirements, a specifically tailored patient
      intervention based on the individual's risk profile appears more likely to
      improve patient outcome compared with general interventions given to the entire
      patient group.

PMID- 20674395
TI  - Does preoperative B-type natriuretic peptide better predict adverse outcome and
      prolonged length of stay than the standard European System for Cardiac Operative
      Risk Evaluation after cardiac surgery?
AB  - OBJECTIVES: Although B-type natriuretic peptide (BNP) strongly predicts cardiac
      morbidity and mortality, the European System for Cardiac Operative Risk
      Evaluation (EuroSCORE) has a modest predictive value to identify a composite
      operative risk after cardiac surgery. The authors tested the hypothesis that a
      single preoperative BNP measurement would be superior to standard EuroSCORE in
      predicting composite adverse outcomes after cardiac surgery. DESIGN: A
      prospective observational study. SETTING: A teaching university hospital.
      PARTICIPANTS: Two hundred eight adult patients. INTERVENTIONS: Conventional
      cardiac surgery with cardiopulmonary bypass. MEASUREMENTS AND MAIN RESULTS: The
      preoperative additive EuroSCORE and BNP measurement were performed in all
      patients. Postoperative nonfatal major adverse cardiac events (malignant
      ventricular arrhythmia, myocardial infarction, and cardiac dysfunction), all
      cause mortality, and prolonged lengths of stay were chosen as study endpoints.
      Predictive abilities of both EuroSCORE and BNP were assessed using logistic
      regression and compared with receiver operating characteristic (ROC) curves.
      Thirty-six (17%, 95% confidence interval [CI], 12%-22%) patients experienced 49
      events over the study period. The areas under the ROC curves assessing the
      utility of EuroSCORE and BNP in predicting adverse outcome and prolonged in
      hospital stay were 0.59 (95% CI, 0.48-0.69) versus 0.76 (95% CI, 0.68-0.85; p <
      0.001) and 0.65 (95% CI, 0.57-0.74) versus 0.71 (95% CI, 0.63-0.80; p = 0.147),
      respectively. Using logistic regression, BNP considered as a dichotomized
      variable was the only independent predictor of adverse cardiac outcome (adjusted
      odds ratio = 10.7; 95% CI, 4.1-27.8; p < 0.001). CONCLUSIONS: Preoperative BNP
      measurement is a strong, independent, and more accurate predictor of adverse
      outcome than EuroSCORE in patients undergoing cardiac surgery. BNP could be
      considered as a simple and objective tool for the detection of high-risk patients
      after cardiac surgery.

PMID- 20674396
TI  - Effect of preservation solution choice on antibody-mediated rejection after heart
      transplantation.

PMID- 20674397
TI  - Aortic valve pathophysiology during left ventricular assist device support.
AB  - The increased applicability and excellent results with left ventricular assist
      devices (LVADs) have revolutionized the available treatment options for patients
      with advanced heart failure. Pre-existing valve abnormalities are common in this
      population, and subsequent development of valve abnormalities after LVAD
      placement is also often noted. Although native mitral and tricuspid valve disease
      is more common in heart failure patients before LVAD placement, aortic valves are
      much more likely to generate abnormal pathophysiology in the LVAD patient during
      as well as after LVAD placement. The aim of this comprehensive review is to
      review aortic valve function in LVAD patients and highlight the consideration of
      pre-existing valve disease on patient treatment at the time of LVAD implant. The
      basis for structural changes leading to valve pathophysiology during and after
      LVAD placement will be described, providing a basis for improved clinical
      understanding and new strategies to prevent these conditions.

PMID- 20674398
TI  - Early presentation of de novo high grade glioma with epileptic seizures:
      electroclinical and neuroimaging findings.
AB  - We report the clinical, EEG and neuroradiologic findings from three adult
      patients who developed new-onset seizure disorders as early clinical
      manifestations of de novo high grade glioma. The malignancies could not be
      recognised at the time of the first epileptic seizure because of minimal non
      specific brain abnormalities, which showed no signs of necrosis or significant
      contrast enhancement on computed tomography and magnetic resonance imaging. Focal
      EEG abnormalities were recorded in all cases and appeared consistent with the
      neuroradiologic findings. The patients regained normal neurological status after
      the first seizure but rapidly developed space-occupying necrotic lesions. Two
      patients underwent surgery and received histological diagnoses of the tumours.
      Another patient was finally diagnosed with a malignant glioma based on the
      neuroradiologic picture and rapid progression of the cerebral lesion. It should
      be noted that in adult patients, new-onset epileptic seizures might reveal the
      presence of malignant gliomas at a very early stage in the tumour formation
      process. This report indicates that typical anatomoradiologic features of de novo
      high grade glioma, such as necrosis and rim-contrast enhancement, could be absent
      at the time of the first epileptic seizure but become clear within a short period
      after clinical presentation.

PMID- 20674399
TI  - De novo generalised non-convulsive status epilepticus triggered by
      piperacillin/tazobactam.

PMID- 20674400
TI  - The kickstand technique for circular external fixator assembly.
AB  - External fixation has been shown to be an extremely versatile tool for surgical
      reconstruction of the lower extremity. Modern circular-ring fixators, based on
      original Ilizarov design, are widely used for their stiffness, utility,
      adjustability, and effectiveness. Because of the full-radius enclosure of the
      limb, however, it can be difficult to place the fixator on a supine patient. Our
      institutions have used a useful technique to aid application of the fixator by
      suspending the limb several centimeters above the operating table.

PMID- 20674401
TI  - Interferon-regulatory factor 4 is essential for the developmental program of T
      helper 9 cells.
AB  - Interferon-regulatory factor 4 (IRF4) is essential for the development of T
      helper 2 (Th2) and Th17 cells. Herein, we report that IRF4 is also crucial for
      the development and function of an interleukin-9 (IL-9)-producing CD4(+) T cell
      subset designated Th9. IRF4-deficient CD4(+) T cells failed to develop into IL-9
      producing Th9 cells, and IRF4-specific siRNA inhibited IL-9 production in wild
      type CD4(+) T cells. Chromatin-immunoprecipitation (ChIP) analyses revealed
      direct IRF4 binding to the Il9 promoter in Th9 cells. In a Th9-dependent asthma
      model, neutralization of IL-9 substantially ameliorated asthma symptoms. The
      relevance of these findings is emphasized by the fact that the induction of IL-9
      production also occurs in human CD4(+) T cells accompanied by the upregulation of
      IRF4. Our data clearly demonstrate the central function of IRF4 in the
      development of Th9 cells and underline the contribution of this T helper cell
      subset to the pathogenesis of asthma.

PMID- 20674402
TI  - SAP protein-dependent natural killer T-like cells regulate the development of
      CD8(+) T cells with innate lymphocyte characteristics.
AB  - CD8(+) T cells are selected via low-affinity interaction with MHC class I
      molecules on thymic epithelial cells (TECs). However, compromised T cell receptor
      signaling was proposed to force CD8(+) T cell selection on hematopoietic cells
      through a SLAM-associated protein (SAP)-dependent mechanism similar to NKT cells.
      The outcome is an unconventional CD8(+) T cell with phenotypic and functional
      characteristics of innate lymphocytes. Here we showed that Id3(-/-) CD8(+) T
      cells had an innate-like phenotype and required SAP for their development.
      However, like conventional CD8(+) T cells, Id3(-/-) CD8(+) thymocytes were
      selected on TECs. The requirement for SAP and the innate-like phenotype was not
      intrinsic to Id3(-/-) CD8(+) thymocytes. Rather, an expanded population of NKT
      like cells induced the innate phenotype on CD8(+) T cells through production of
      interleukin-4. Our findings reveal that accumulation of NKT-like cells promotes
      conventional CD8(+) thymocytes to acquire innate lymphocyte characteristics.

PMID- 20674403
TI  - Peripheral odontogenic fibroma: a clinicopathologic study of 151 cases and review
      of the literature with special emphasis on recurrence.
AB  - OBJECTIVE: The peripheral odontogenic fibroma (POdF) is a rare benign neoplasm of
      odontogenic origin with limited data on recurrence. The purpose of this study was
      to define the clinical and histopathologic spectrum of POdF and to investigate
      its recurrence rate and variables associated with its recurrence. STUDY DESIGN: A
      total of 151 cases of POdF were accepted for this study, which documented
      clinical, histopathologic, and follow-up data. Multivariate stepwise logistic
      regression was used to investigate the association of categorical variables and
      recurrence. RESULTS: POdF should be considered a mixed odontogenic tumor because
      it is composed of active odontogenic epithelial and ectomesenchymal components.
      Of the 58 cases with follow-up, 29 recurred. Budding of the basal cell layer of
      the surface squamous epithelium was associated with higher recurrence (P=.0186);
      27 cases with recurrence which exhibited this feature. The presence of
      calcification in direct apposition to epithelial rests was associated with lower
      recurrence (P=.0076); 13 cases that did not recur exhibited this feature.
      CONCLUSIONS: POdF has a 50% recurrence rate. Budding of the surface epithelium
      and calcification in apposition to odontogenic epithelial rests are histologic
      predictors of recurrence.

PMID- 20674404
TI  - Predicting risk for bisphosphonate-related osteonecrosis of the jaws: CTX versus
      radiographic markers.
AB  - BACKGROUND AND OBJECTIVE: The most common risk factor for bisphosphonate-related
      osteonecrosis of the jaws (BRONJ) is dentoalveolar surgery. It has been suggested
      that reduced serum C-terminal telopeptide (CTX) can determine the degree of
      osteoclast suppression and may predict the development of BRONJ after
      dentoalveolar surgery. Although there are many radiographic appearances
      associated with BRONJ, there are little data that describes changes preceding
      dentoalveolar surgery. The objective of this retrospective study was: 1) to
      investigate if reduced serum CTX values (i.e., <150 pg/mL) were associated with
      BRONJ after dentoalveolar surgery; and 2) to determine if specific radiographic
      changes are associated with teeth that develop BRONJ after extraction. STUDY
      DESIGN: A retrospective review of radiographic and/or serum CTX data was
      performed for 68 patients with a history of bisphosphonate therapy who either
      underwent dental extraction or were diagnosed with BRONJ in the Department of
      Oral and Maxillofacial Surgery during the period 2007-2009. Postoperative healing
      was assessed for 26 patients with reduced serum CTX levels (<150 pg/mL) who
      either underwent dental extraction or treatment for BRONJ. Preoperative
      radiographs were evaluated for 55 patients who either healed normally or
      developed BRONJ after dental extraction. RESULTS: All 26 patients (100%) who had
      serum CTX levels <150 pg/mL healed successfully after dentoalveolar surgery (20
      patients) or after treatment for BRONJ (6 patients). Among the 55 patients who
      underwent radiographic evaluation, 24 patients (83%) with BRONJ exhibited
      periodontal ligament (PDL) widening associated with extracted teeth, whereas only
      3 patients (11%) who healed normally demonstrated PDL widening. CONCLUSION: These
      data suggest that radiographic PDL widening may be a more sensitive indicator
      than CTX testing in predicting risk of BRONJ. Current guidelines that recommend
      minimal surgical intervention may need to be revised to include alternative
      strategies for the elimination or management of this pathology.

PMID- 20674405
TI  - Comparison of flap and flapless procedures for the stability of chemically
      modified SLA titanium implants: an experimental study in a canine model.
AB  - BACKGROUND: Flapless implant surgery has been shown to accelerate recovery and
      increase the vascularity of the peri-implant mucosa after implant placement.
      OBJECTIVE: The aim of this study was to compare dental implant stabilization
      patterns between flap and flapless implant surgeries over the first 8 weeks after
      implant placement. STUDY DESIGN: In 6 mongrel dogs, bilateral, edentulated, and
      flat alveolar ridges were created in the mandible. After 3 months of healing, 2
      implants (Straumann SLA-active) were placed in each side of the mandible using
      either a flap or flapless procedure. The implant stability quotient (ISQ) that
      was obtained from Osstell Mentor was measured at the time of implantation and
      weekly over the first 8 weeks after implant placement. RESULTS: Implants
      stabilized more quickly without flap elevation than with flap elevation. For
      flapless implants, an increase in stability occurred after 2 weeks without a
      period of decreasing stability. However, for flap implants, a shift in implant
      stability from decreasing stability to increasing stability occurred after 2
      weeks. CONCLUSION: In the canine model, flapless surgical placement of implants
      may increase the initial stability of implants compared with implants placed
      after the reflection of the mucoperiosteal flap.

PMID- 20674406
TI  - Predisposition of allergy in patients with benign migratory glossitis.
AB  - OBJECTIVE: The purpose of this study was to investigate the presence of allergy
      in patients with benign migratory glossitis (BMG) using patch and prick tests.
      PATIENTS AND METHODS: Eighty patients (40 BMG and 40 healthy controls) received
      patch and prick tests. If at least one test result was positive, patients were
      considered to be allergic. RESULTS: The prick test was positive in 10 patients
      (25.0%) of the study group and in 4 patients (10.0%) of the control group. The
      patch test was positive in 12 patients (30.0%) of the study group and in 6
      patients (15.0%) of the control group. When results of both tests were evaluated
      together, the study group showed a positive rate of 47.5% (n = 19), whereas the
      control group showed a positive rate of 22.5% (n = 9) (P = .02). CONCLUSION: Our
      results revealed that a combination of prick and patch tests can significantly
      enhance the diagnostic accuracy of predisposition of allergy in patients with
      BMG.

PMID- 20674407
TI  - Implant-supported restoration of congenitally missing teeth using cancellous bone
      block-allografts.
AB  - BACKGROUND AND OBJECTIVE: Patients with congenitally missing teeth may present
      with undeveloped alveolar bone morphology, making implant reconstruction a
      challenge. The aim of the present study was to evaluate the outcome of dental
      implants after ridge augmentation with cancellous freeze-dried block bone
      allografts in patients with congenitally missing teeth. STUDY DESIGN: Twelve
      patients with a mean age of 21 +/- 4 years, were included. Congenitally missing
      teeth included maxillary lateral incisors, a maxillary canine, and mandibular
      central and lateral incisors. A bony deficiency of >=3 mm horizontally and <=3 mm
      vertically according to computerized tomography served as inclusion criteria.
      Twenty-one implants were inserted after a healing period of 6 months. Five out of
      21 implants were immediately restored. Bone measurements were taken before bone
      augmentation, during implant placement, and at second-stage surgery. RESULTS:
      Nineteen cancellous allogeneic bone-blocks were used. The mean follow-up time was
      30 +/- 16 months. Bone block and implant survival rates were 100% and 95.2%,
      respectively. Mean bone gain was statistically significant (P < .001): 5 +/- 0.5
      mm horizontally and 2 +/- 0.5 mm vertically. All of the patients received a fixed
      implant-supported prosthesis. Soft tissue complications occurred in 4 patients
      (30%). Complications after cementation of the crowns were seen in 1 implant
      (4.8%). All implants remained clinically osseointegrated at the end of the follow
      up examination. There was no crestal bone loss around the implants beyond the
      first implant thread. CONCLUSION: Cancellous bone block-allografts can be used
      successfully for implant-supported restorations in patients with congenitally
      missing teeth.

PMID- 20674408
TI  - The hazards of gutka chewing.

PMID- 20674409
TI  - Use of botulinum toxin A for drug-refractory trigeminal neuralgia: preliminary
      report.
AB  - OBJECTIVE: Botulinum toxin type A (BTX-A) has been used to treat migraine and
      occipital neuralgia. We report preliminary results of an ongoing study that
      assesses the efficacy of BTX-A on trigeminal neuralgia (TN) patients refractory
      to medical treatment. STUDY DESIGN: We treated 15 patients (8 men and 7 women)
      between 28 and 67 years of age who were suffering from drug-refractory TN from
      February 2008 to January 2010. Symptoms, including pain duration, provoking
      factors, affected nerve branch, frequency of TN attacks, and severity of pain
      just before injections, were evaluated 1 week, 1 month, and 6 months after
      injection. We injected 50 U reconstituted BTX-A solution at the trigger zones.
      The overall response to treatment was assessed via a 9-point patient global
      assessment scale and compared with values at baseline. Statistical analysis was
      performed by the analysis of variance (ANOVA) test for frequency of TN attacks,
      the Friedman test for severity of pain, and the Wilcoxon signed-rank test for
      PGA, and all with the use of SPSS software. RESULTS: Eight men and 7 women aged
      28-67 years (mean 48.9 y) suffering from TN from 6 months to 24 years all
      improved regarding frequency and severity of pain attacks; in 7 patients, pain
      was completely eradicated and there was no need for further medication. In 5
      patients, nonsteroidal antiinflammatory drugs were enough to alleviate pain
      attacks, and 3 patients again responded to anticonvulsive drugs after injection.
      All patients developed higher pain thresholds after injections. The ANOVA test
      showed a significant difference in frequency of attacks before injection and at 1
      week, 1 month, and 6 months after injection (P < .001). Friedman test and pair
      comparison of pain severity scores with Bonferroni correction adjustment showed a
      significant difference (P < .001) between severity of pain before and after
      injection. Wilcoxon signed-rank test showed significant improvement in all
      patients up to 6 months after injection (P < .001). Complications included
      transient paresis of the buccal branch of the facial nerve in 3 patients.
      CONCLUSION: This study supports other similar studies and shows that BTX-A is a
      minimally invasive method that can play a role in treating TN before other more
      invasive therapies, i.e., radiofrequency and surgery.

PMID- 20674411
TI  - The role of surgical therapy in the management of intravenous bisphosphonates
      related osteonecrosis of the jaw.
AB  - OBJECTIVES: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) seems
      resistant to conventional treatment approaches. We report a study with a surgical
      concept characterized by resection of the necrotic bone followed by sufficient
      wound closure. STUDY DESIGN: In a clinical study of 24 patients with 33 sites of
      BRONJ, the surgical basis of the treatment was as follows: (1) conservative
      treatment with antimicrobiological rinsing, (2) resection of the entire necrotic
      bone and smoothening of any sharp bone edges, and (3) coverage of the remaining
      bone by use of a bilayered wound closure. RESULTS: In 88% of cases, BRONJ could
      be treated with success by use of this surgical therapy. Median follow-up was 60
      weeks. There was no statistically significant difference between treatment
      results irrespective of whether or not bisphosphonate treatment was continued.
      CONCLUSION: Because of the high success rate of this surgical technique it seems
      that patients with BRONJ may benefit from this approach.

PMID- 20674412
TI  - Oral focal mucinosis associated with cervical external root resorption: a case
      report.
AB  - BACKGROUND: Oral focal mucinosis (OFM) and cervical external root resorption are
      both rare lesions with an unknown etiology. In this article we report on a rare
      occurrence of OFM associated with cervical external root resorption. METHODS: A
      44-year-old female patient presented with sharp pain while drinking cold
      beverages and a firm localized gingival overgrowth adjacent to the buccal aspect
      of tooth #19. An excisional biopsy of the gingival lesion was taken and a deep
      cavity was found in the buccal aspect of the root. The cavity was restored with
      an amalgam filling. RESULTS: The histological findings were of a well
      circumscribed lesion composed of myxomatous connective tissue, which contained
      numerous stellate-shaped fibroblasts. Based on the findings, a diagnosis of OFM
      was made. CONCLUSION: A rare case of OFM and cervical external root resorption
      occurring in the same site was described. A possible link between these 2
      phenomena was hypothesized.

PMID- 20674413
TI  - Effect of different water flows on root surface temperature during ultrasonic
      removal of posts.
AB  - OBJECTIVE: This in vitro study evaluated rises in temperature on the outer root
      surface of human incisors during ultrasonic post removal with different water
      flows. STUDY DESIGN: Thirty-six extracted teeth (12 maxillary central incisors,
      12 maxillary lateral incisors, and 12 mandibular incisors) were used. After root
      canal preparation, the teeth were obturated, and prefabricated posts were
      cemented into the prepared spaces. Posts were ultrasonically instrumented dry and
      with irrigation at 20 mL/min and 40 mL/min. Temperature changes on the entire
      mesial outer surfaces of the roots were measured at 10-second intervals using an
      infrared thermal imaging camera. RESULTS: Increases in root surface temperature
      were significantly lower when posts were instrumented with 40 mL/min water
      irrigation compared with dry vibration and 20 mL/min irrigation, which also
      significantly differed from each other. Statistical analysis among tooth groups
      showed differences in the mean temperature rise of maxillary central incisors and
      maxillary lateral incisors compared with mandibular incisors when posts were
      instrumented dry or with 20 mL/min irrigation. There were no significant
      differences in mean temperature rises between the studied groups when 40 mL/min
      irrigation was used. CONCLUSIONS: Water cooling during ultrasonic post
      instrumentation significantly reduced temperature increases on the outer root
      surface; however, the intensity of the cooling was also important. Our results
      suggest that copious water irrigation during post removal is an effective method
      to protect the root's surrounding tissue.

PMID- 20674414
TI  - Adrenal crisis provoked by dental infection: case report and review of the
      literature.
AB  - Primary adrenal insufficiency is an endocrine disorder characterized by cortisol
      and aldosterone deficiency caused by destruction of the adrenal cortex. Adrenal
      crisis is a medical emergency with acute symptoms: nausea, vomiting, abdominal
      pain, fever, hypoglycemia, seizures, hypovolemic shock, and cardiovascular
      failure. It occurs in patients with chronic adrenal insufficiency who are exposed
      to additional stress, such as infection, trauma, or surgical procedures. Dental
      infection is a possible cause of adrenal crisis in patients with chronic adrenal
      insufficiency, so pediatric endocrinologists and pediatric dentists should be
      aware of this risk. The purpose of this report was to present a 6-year-old
      patient in whom Addison disease was diagnosed through adrenal crisis provoked by
      dental infection. The patient was treated with intravenous rehydration,
      intravenous hydrocortisone and antibiotics, and extraction of the infected
      primary tooth. Multidisciplinary approach and collaboration between the pediatric
      endocrinologist and the pediatric dentist are necessary to enable adequate
      medical and dental treatment in children with primary adrenal insufficiency.

PMID- 20674415
TI  - Genetic analysis of intraoral KIT-positive gastrointestinal stromal tumor (GIST).
AB  - Gastrointestinal stromal tumors (GISTs), mesenchymal neoplasms originating from
      the cells of Cajal, usually appear in the gastrointestinal tract and abdomen.
      They often mimic other lesions, including smooth muscle cell tumors and
      neurogenic tumors. This study presents a case in which a GIST appeared over a 2
      month period and was treated by excision and curettage, with no sign of
      recurrence during the next 42 months. The study also aims to characterize the
      GIST. Histopathologic analysis and KIT gene amplification and sequencing were
      performed. On mutation analysis of the GIST material, the novel 69338Tdel
      mutation was found in exon 11, and the diagnosis of intraoral stromal tumor was
      made. GISTs in the intraoral region display pathologic properties similar to
      others developed throughout the gastrointestinal system. Diagnosis is the first
      step of treatment for a patient. The discovery of oncogenic KIT mutations in
      GISTs has led to the development of targeted molecular therapy using tyrosine
      kinase inhibitors. This study investigates the histopathologic and molecular
      diagnostics of GISTs, and, to the authors' knowledge, it represents the first
      genetic study of a GIST developing in the intraoral region.

PMID- 20674416
TI  - Orthodontic extrusion of the lower third molar with an orthodontic mini implant.
AB  - Neurologic changes owing to damage to the inferior alveolar nerve (IAN) are the
      most serious complication of lower third molar (M3) extraction because of their
      close spatial relationship. We adopted the concept of regional orthodontic
      treatment and extrusion, using skeletal anchorage with an orthodontic mini
      implant. Two malformed M3s that were closely apposed to the IAN were extruded
      with the aid of 3 or 4 orthodontic brackets and a mini implant. Both of the M3s
      were extruded successfully. The patients experienced little discomfort with the
      orthodontic appliances and there was neither permanent neurologic damage nor
      fracture of the root fragments following subsequent M3 extraction. Orthodontic
      treatment using a miniscrew to separate the IAN and M3, or luxation of the M3 may
      be a good alternative treatment option for extrusion of a vertically impacted
      lower M3 with fragile roots.

PMID- 20674417
TI  - Comparison of ondansetron and metoclopramide antiemetic prophylaxis in
      maxillofacial surgery patients.
AB  - PURPOSE: The purpose of this study was to compare the efficacy of ondansetron and
      metoclopramide, administered for the prophylaxis of vomiting in patients
      undergoing oral and maxillofacial surgery under general anesthesia. METHODS: One
      hundred patients undergoing mandibular osteotomy surgery were studied. Patients
      were allocated randomly to receive 1 of 2 treatment regimens: 0.15 mg/kg
      ondansetron or 0.5 mg/kg metoclopramide intravenously 30 minutes before
      extubation. All were adults and were treated by one surgeon and all operations
      were the same and lasted 2.5 to 3.0 hours. The patients were assessed at 3 time
      periods: 0 to 3 hours, 3 to 12 hours, and 12 to 24 hours postoperatively for
      emesis. RESULT: The data from this study showed that during the first 24-hour
      postoperative period, patients receiving ondansetron following general anesthesia
      had an 11% (11 patients) incidence of emesis compared with 28% (22 patients) in
      the group that received metoclopramide. CONCLUSION: In this study, ondansetron
      (0.1 mg/kg) was twice as effective in preventing postoperative vomiting compared
      with metoclopramide.

PMID- 20674418
TI  - Oral ulcer associated with alendronate: a case report.
AB  - Irritation of the mucosa of the aerodigestive tract is a well-known adverse
      effect of alendronate, whereas oral ulceration has been reported in only 14
      articles in both the English and non-English literature. All of these have been
      associated with misuse of the drug. We here present the first case of severe oral
      ulceration attributable to use of alendronate without inappropriate therapeutic
      administration of the medication.

PMID- 20674419
TI  - SAPHO syndrome with affection of the mandible: diagnosis, treatment, and review
      of literature.
AB  - The synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a
      rare syndrome of unknown etiology. Involvement of the mandible is found in almost
      10% of cases. In the literature, conservative treatment is recommended most
      often, because decortication and partial resection are found to be ineffective
      and of temporary profit. We report a case of SAPHO syndrome in a 44-year-old
      women with unilateral hyperostosis of the mandible and massive painful swelling
      of the surrounding soft tissues. Owing to facial disfiguration and pain,
      resection of the affected bone followed by immediate reconstruction with a
      microvascular iliac crest flap were performed. The aim of this paper was to
      present the necessity of surgical intervention in SAPHO syndrome of the mandible
      in cases of esthetic and functional limitation.

PMID- 20674420
TI  - Time to abandon the term angiomyolipoma for non-PEComatous angiomyomatous (or
      angiomatous) oral tumors with adipocytes.
AB  - Angiomyolipoma (AML) is the most common benign mesenchymal neoplasm of the
      kidneys with well-established clinical and morphological features. The oral and
      maxillofacial pathology literature contains several examples that identify
      angiomyomatous proliferations of the oral mucosa that contain an adipocytic
      component as analogous to classic renal AMLs although they differ significantly
      in their immunohistochemical phenotype. Herein, through review of the pertinent
      oral pathology literature and the detailed description of 2 lesions, one an oral
      angiomyoma with an adipocytic component and the other an apparently hamartomatous
      angioleiomyomatous proliferation with adipocytes, we provide, in our opinion, a
      solid argument against the use of the term AML for non-PEComatous oral tumors.

PMID- 20674421
TI  - Contrast STRAFI-MAS imaging.
AB  - We demonstrate the possibility of multidimensional contrast (T(1)-, T(2)-weighted
      and triple-quantum filtered) magnetic resonance imaging using a simple and
      effective solid-state NMR technique, stray-field imaging with sample magic-angle
      spinning (STRAFI-MAS). This imaging technique can be easily implemented in
      today's standard solid-state NMR laboratory, making it a potentially valuable
      imaging application to material science.

PMID- 20674423
TI  - Breast milk and gene delivery: is lysinuric protein intolerance an exemplar?

PMID- 20674422
TI  - Dynamic-contrast-enhanced-MRI with extravasating contrast reagent: rat cerebral
      glioma blood volume determination.
AB  - The accurate mapping of the tumor blood volume (TBV) fraction (vb) is a highly
      desired imaging biometric goal. It is commonly thought that achieving this is
      difficult, if not impossible, when small molecule contrast reagents (CRs) are
      used for the T1-weighted (Dynamic-Contrast-Enhanced) DCE-MRI technique. This is
      because angiogenic malignant tumor vessels allow facile CR extravasation. Here, a
      three-site equilibrium water exchange model is applied to DCE-MRI data from the
      cerebrally-implanted rat brain U87 glioma, a tumor exhibiting rapid CR
      extravasation. Analyses of segments of the (and the entire) DCE data time-course
      with this "shutter-speed" pharmacokinetic model, which admits finite water
      exchange kinetics, allow TBV estimation from the first-pass segment. Pairwise
      parameter determinances were tested with grid searches of 2D parametric error
      surfaces. Tumor blood volume (vb), as well as ve (the extracellular,
      extravascular space volume fraction), and Ktrans (a CR extravasation rate
      measure) parametric maps are presented. The role of the Patlak Plot in DCE-MRI is
      also considered.

PMID- 20674424
TI  - Oligodendroglia from ADSL-deficient patient produce SAICAribotide and SAMP.
AB  - Succinylpurines accumulate in the body fluids of patients with adenylosuccinate
      lyase (ADSL) deficiency but their source in the cerebrospinal fluid remains
      obscure. Study based on the incorporation of 13C-stable isotope-labeled glycine
      into cultured oligodendroglia from ADSL-deficient patient and the measurement of
      labeled products by LC/MS/MS showed total intracellular concentrations of
      succinylpurines from 45 to 99MUmol/l and so these results suggest that these
      cells can be the source of the compounds in vivo.

PMID- 20674425
TI  - Thiamine deficiency in a cat: resolution of MRI abnormalities following thiamine
      supplementation.
AB  - Thiamine (vitamin B(1)) is an essential component of a number of metabolic
      pathways and thiamine deficiency results in a progressive encephalopathy in both
      humans and animals. Confirming thiamine deficiency is problematic and relies on
      demonstrating reduced red blood cells transketolase activity, or indirect methods
      including urinary organic acid analysis and dietary analysis. The characteristic
      and selective vulnerability of different brain regions in carnivores has been
      demonstrated by magnetic resonance (MR) imaging in the dog and cat as an aid to
      diagnosis. A 2-year-old, female, domestic shorthair cat was presented with an
      acute onset of seizures and ataxia. MR imaging was consistent with thiamine
      deficiency and supplementation resulted in a progressive clinical improvement.
      Repeated MR imaging 4 days after starting thiamine supplementation revealed near
      complete resolution of the MR abnormalities. Repeated MR imaging following
      appropriate therapy may be useful to further confirm thiamine deficiency.

PMID- 20674426
TI  - Myelitis due to reactivated spinal toxoplasmosis in a cat.
AB  - The diagnosis, management, and subsequent post-mortem confirmation of a case of
      suspected reactivated spinal toxoplasmosis in a 10-year-old female neutered
      Cornish Rex are described. While an ante-mortem diagnosis of toxoplasmosis was
      considered possible based on the neuroanatomical diagnosis of central nervous
      system (CNS) disease primarily involving spinal cord segment C6-T2 and the
      progressive elimination of other potential causes, Toxoplasma gondii antibody
      titres were consistent with previous exposure rather than active infection. A
      poor response to appropriate therapy did not support a diagnosis of
      toxoplasmosis. A post-mortem morphological diagnosis of marked segmental non
      suppurative myelitis and necrosis, and an aetiological diagnosis of toxoplasmosis
      were made. The clinical and pathological findings are supportive of CNS
      inflammation due to reactivation of latent tissue T gondii cysts.

PMID- 20674427
TI  - Epidermal growth factor receptor expression is predictive of poor prognosis in
      feline cutaneous squamous cell carcinoma.
AB  - The aim of this study was to investigate epidermal growth factor receptor (EGFR)
      expression in feline cutaneous squamous cell carcinoma (FC-SCC) and assess its
      prognostic role. Nineteen formalin-fixed paraffin-embedded excisional biopsies of
      FC-SCC were tested for EGFR expression using immunohistochemistry (IHC).
      Relationships between EGFR expression and histopathological parameters
      (differentiation, mitotic activity), disease-free interval (DFI) and overall
      survival (OS) at 24 months were further investigated. Fourteen of 19 tumours
      (73.7%) were positive for EGFR, with great variation in intensity and proportion
      of labelled cells. EGFR expression was not correlated with tumour differentiation
      or mitotic activity. Nine cats (47.4%) died of tumour-related causes. Patients
      with EGFR-positive tumours had a significantly worse outcome (P=0.0217), with
      decreased DFIs (P=0.0075) and survival times (P=0.0391). These data suggest that
      EGFR expression carries a negative prognostic significance in FC-SCC. EGFR
      inhibitors in association with conventional treatments may improve outcome for
      the subgroup of cats with EGFR-positive tumours.

PMID- 20674428
TI  - Detection of Tritrichomonas foetus in cats in Greece.
AB  - Intestinal infection of cats with Tritrichomonas foetus has been reported in the
      USA, Canada, several European countries, and Australia. However, T foetus has not
      been previously reported in cats in Greece. The aim of this study was to test
      fecal samples from cats living in Greece for the presence of T foetus DNA. Feces
      were collected from 31 cats living in Greece. DNA was extracted from the fecal
      samples and the presence of T foetus DNA was detected by a single-tube nested
      polymerase chain reaction (PCR). T foetus specific DNA was detected in the feces
      of 6/30 (20.0%) cats. All six cats were reported to have normal fecal quality at
      the time of sample collection and five of them were adults. The present study
      confirms for the first time the presence of T foetus in cats in Greece and
      suggests that T foetus infection is often asymptomatic in older cats.

PMID- 20674429
TI  - Evaluation of dose area product vs. patient dose in diagnostic X-ray units.
AB  - Dose Area Product (DAP) meters which measure in units of [Gy*m(2)], are widely
      used in radiology, fluoroscopy and interventional cardiology X-ray units.
      However, assessment of the radiological hazard to the patient undergoing a given
      diagnostic procedure cannot be readily obtained from the measured value of DAP.
      We also developed simple relationships between Entrance Surface Dose (ESD) and
      the DAP value measured in air, for different collimator field sizes and patient
      thickness. To establish these relationships, measurements were performed in a
      water phantom using high-sensitive thermoluminescent detectors (LiF:Mg,Cu,P)
      calibrated in terms of Kerma in water. Using these relationships developed for a
      given X-ray unit, calculations of ESD (in mGy) could be performed on the basis of
      DAP by the X-Ray unit software itself, if the X-ray unit could also evaluate the
      Focus-to-Skin Distance (FID), e.g. by ultra-sound techniques.

PMID- 20674430
TI  - [Perception of ethical attitudes of intensive care nurses on treatment
      limitation].
AB  - OBJECTIVE: Analyze the perception of intensive care nurses regarding the
      limitation of therapeutic efforts (LET). METHOD: A 2-month cross-sectional,
      descriptive study carried out among Intensive Care nursing staff of our Hospital.
      An anonymous survey was used to assess the attitudes of intensive care nurses on
      LET. RESULTS: Fifty-two nurses (86.6%), 57.7% women, with a working experience of
      8.8+/-4.8 years and 17.7%, had some additional training in ethics. The decision
      not to hospitalize a patient whose short term quality of life is very poor
      changes when the patient's opinion is considered (36.5% vs 61.5%, p=0.008), a
      difference that is greater in male nurses without prior training in ethics. A
      total of 23.1% were not aware of the existence of agreed on guidelines on LET in
      the Service. A total of 17.3% consider that limiting treatment, either by not
      providing it or by withdrawing it, is a form of passive euthanasia, which would
      be an acceptable practice as opposed to euthanasia and 84.6% consider that
      administering a treatment is not the same as withdrawing it. Of those surveyed,
      36.5% felt that the neither the nursing staff should not participate in the
      decision to limit treatment nor the patients (34.6%) nor family (23.1%).
      CONCLUSIONS: Nursing is not aware of the importance it can have, along with the
      family and patient, in decision making in relationship to the limitation of the
      treatment of the critical patient, providing a humanizing and ethical view of the
      care.

PMID- 20674431
TI  - HIV clinical pharmacists--the US perspective.
AB  - Clinical pharmacists have been involved in treating people with HIV and AIDS
      since the epidemic began. Their roles have evolved from inpatient infectious
      diseases training clinical pharmacists offering treatment regimens for the
      serious opportunistic infections seen in the hospital, to clinical pharmacists
      who received specialized training in the treatment of people with HIV in the
      ambulatory care setting. Their roles and benefits have been documented in the
      literature, but not to a large extent. Improvements in adherence and cost savings
      have been seen, but significant improvements in clinical outcomes (changes in
      viral load and CD4 cell counts) are quite complex and often difficult to identify
      in the small studies that have been published. This manuscript will review the
      published data on this topic, and provide examples of clinically trained
      pharmacists in the US who focus on the treatment of people with HIV infection.
      The pharmacists discussed here practice in a variety of settings (privately
      managed free-clinics and government managed clinics), take care of a variety of
      types of patients (children, adults, military veterans, lower socio-economic
      groups, etc.), and are employed by a variety of institutions (academic,
      pharmaceutical company, large healthcare systems and small healthcare systems).
      These pharmacists were chosen to be representative of the wide variety of
      individuals, positions and roles of clinical pharmacists involved in the
      treatment of HIV in the US.

PMID- 20674432
TI  - Hepatitis B virus genotyping: current methods and clinical implications.
AB  - Hepatitis B virus (HBV) is a major cause of liver cirrhosis and hepatocellular
      carcinoma (HCC). Eight different HBV genotypes have been identified with distinct
      geographical distributions. Different genotyping methods exist including
      sequencing, INNO-LiPA, restriction fragment polymorphism (RFLP), multiplex PCR,
      serotyping, oligonucleotide microarray chips, reverse dot blot, restriction
      fragment mass polymorphism (RFMP), invader assay, and real-time PCR. Several
      investigators have studied the influence of HBV genotypes on clinical outcomes in
      chronic HBV patients. This review describes the current genotyping techniques, as
      well as their advantages and limitations. It also presents the clinical evidence
      that correlates HBV genotypes to clinical outcomes including disease severity,
      HCC development, response to therapy, disease chronicity, transplantation
      outcomes, and occult infection.

PMID- 20674435
TI  - Red cell membrane and malaria.
AB  - Malaria is the most serious and widespread parasitic disease of humans, with up
      to 500 million people being infected each year with malaria parasites and a
      million individuals, predominantly infants and young children, dying as a
      consequence of the infection. During intra-erythrocytic life cycle of 48h, over
      400 proteins produced by parasites are exported into the red cell cytoplasm and a
      number of these proteins interact with membrane skeleton. Significant progress is
      being made in identifying the binding domains in both parasite proteins and red
      cell proteins that mediate protein-protein interactions. These various parasite
      red cell protein interactions are responsible for striking structural and
      morphological changes in the infected red cell including loss of normal discoid
      shape, perturbations in the rheological and adhesive properties of the cell that
      are responsible for the clinical manifestation of malaria infection, malarial
      anemia and cerebral malaria. It is anticipated these ongoing advances will offer
      opportunities for the discovery of new and urgently needed therapeutic targets
      for the treatment of malaria.

PMID- 20674434
TI  - Metabolomic analysis of normal and sickle cell erythrocytes.
AB  - Metabolic signatures of specialized circulating hematopoietic cells in
      physiological or human hematological diseases start to be described. We use a
      simple and highly reproductive extraction method of erythrocytes metabolites
      coupled with a liquid chromatography-mass spectrometry based metabolites
      profiling method to determine metabolomes of normal and sickle cell erythrocytes.
      Sickle cell erythrocytes and normal erythrocytes metabolomes display major
      differences in glycolysis, in glutathione, in ascorbate metabolisms and in
      metabolites associated to membranes turnover. In addition, the amounts of
      metabolites derived from urea cycle and NO metabolism that partly take place
      within erythrocyte were different between normal and sickle cell erythrocytes.
      These results show that metabolic profiling of red blood cell diseases can now be
      determined and might indicate new biomarkers that can be used for the follow-up
      of sickle cell patients.

PMID- 20674433
TI  - Japanese encephalitis virus remains an important cause of encephalitis in
      Thailand.
AB  - BACKGROUND: Japanese encephalitis virus (JEV) is endemic in Thailand and
      prevention strategies include vaccination, vector control, and health education.
      METHODS: Between July 2003 and August 2005, we conducted hospital-based
      surveillance for encephalitis at seven hospitals in Bangkok and Hat Yai. Serum
      and cerebrospinal (CSF) specimens were tested for evidence of recent JEV
      infection by immunoglobulin M (IgM) enzyme-linked immunosorbent assay (ELISA) and
      a plaque reduction neutralization test (PRNT). RESULTS: Of the 147 patients
      enrolled and tested, 24 (16%) had evidence of acute flavivirus infection: 22
      (15%) with JEV and two (1%) with dengue virus. Of the 22 Japanese encephalitis
      (JE) cases, 10 (46%) were aged <= 15 years. The median length of hospital stay
      was 13 days; one 13-year-old child died. Ten percent of encephalitis patients
      enrolled in Bangkok hospitals were found to have JEV infection compared to 28% of
      patients enrolled in hospitals in southern Thailand (p < 0.01). Four (40%) of the
      10 children with JE were reported as being vaccinated. CONCLUSIONS: JEV remains
      an important cause of encephalitis among hospitalized patients in Thailand. The
      high proportion of JE among encephalitis cases is concerning and additional
      public health prevention efforts or expanded vaccination may be needed.

PMID- 20674436
TI  - [Quality and safety about hemapheresis practicing: from a self-evaluation of
      medical practices to a systematic risk management process].
AB  - Hemapheresis is made up of a set of essential methods for modern medical
      practices. Applicated to donors, they allow production of labile blood products
      as well as raw material for plasma products industrial manufacturing; applicated
      to patients, they are indispensable for the treatment of many pathologies.
      Conditions for their implementation are very variable according to the teams who
      have few tools at their disposal to access, standardize and make reliable their
      activity. Therefore, an approach has been initiated by the Institut National de
      la Transfusion Sanguine and the Hemapheresis French Society to develop a guide
      which primary goal is to help teams evaluate themselves in different areas of
      their responsibilities. The generalization of the evaluation of professional
      practices in all activities and specialties required recently by the third
      iteration of the certification procedure of health institutions and a new law
      about French health system reinforce us in our approach. Finally, hemapheresis is
      not without risks, neither for donors nor for patients, which now encourages us
      to analyze sharply our procedures, to identify risk situations and develop means
      of prevention. This second step is already a current news for us.

PMID- 20674437
TI  - Transport mechanisms in the ammonium transporter family.
AB  - Ammonium transport is mediated by membrane proteins of the ubiquitous Amt/Rh
      family. Despite the availability of different X-ray structures that provide many
      insights on the ammonium permeation process, the molecular details of its
      mechanism remain controversial. The X-ray structures have revealed that the pore
      of the Amt and Rh proteins is characterized by a hydrophobic portion about 12A
      long in which electronic density was observed in crystallographic study of AmtB
      from Escherichia coli. This electronic density was initially only observed when
      crystals were grown in presence of ammonium salt and was thus attributed to
      ammonia (NH(3)) molecules, and lead the authors to suggest that the conduction
      mechanism in the Amt/Rh proteins involves the single-file diffusion of NH(3)
      molecules. However, other X-ray crystallography results and molecular mechanics
      simulations suggest that the pore of AmtB could also be filled with water
      molecules. The possible presence of water molecules in the pore lumen calls for a
      reassessment of the growing consensus that Amt/Rh proteins work as plain NH(3)
      channels. Indeed, functional experiments on plant ammonium transporters and
      rhesus proteins suggest a variety of permeation mechanisms including the passive
      diffusion of NH(3), the antiport of NH(4)(+)/H(+), the transport of NH(4)(+), or
      the cotransport of NH(3)/H(+). We discuss these mechanisms in light of some
      recent functional and simulation studies on the AmtB transporter and illustrate
      how they can be reconciled with the available high resolution X-ray data.

PMID- 20674438
TI  - [Detection of B19 parvovirus in plasma pools before solvent-detergent treatment
      of plasma: AFSSAPS and EFS Aquitaine-Limousin's experience].
AB  - Since 1998, the Aquitaine-Limousin branch of the French Blood Institute has set
      up a parvovirus B19 (PV B19) systematic screening on each unit of plasma to be
      treated by solvent-detergent procedure for virus inactivation. Parvovirus B19
      nucleic acid systematic testing in plasma pools became mandatory since 2005
      (European monograph "Human plasma" - pooled and treated for virus inactivation).
      The French competent state authority (AFSSAPS) has decided to introduce this test
      as a part of the external quality control of labile blood products. This process
      is related to the harmonization of quality control practice realised on blood
      products in Europe even if the human plasma pooled and treated for virus
      inactivation by solvent-detergent is considered in France as a blood labile
      component. Implementation of this test required a validation step and a close
      cooperation between AFSSAPS and Aquitaine-Limousin blood transfusion centre.
      Validation consisted in perfecting a semi-quantitative, real-time nucleic acid
      testing method with automated extraction. This collaborative study leads us to
      control 1642 plasma pools. All the results were under the threshold of 10,0
      IU/microL. AFSSAPS's results were in agreement with those of Aquitaine-Limousin's
      blood transfusion center who carry out the parvovirus B19 screening both on fresh
      frozen plasma units composing the pool and on plasma pools.

PMID- 20674439
TI  - [Stem cell transplantation in Morocco: report of 87 cases].
AB  - PURPOSE: The autologous peripheral blood stem cells (CSP) are used as a support
      to the restoration of the hematopoiesis in oncohematology. The objective of this
      work, carried out in the laboratory of cryobiology at the Center Regional of
      Blood Transfusion, Casablanca, is to assess the short- and long-term results of
      this type of autograft. PATIENTS AND METHODS: This retrospective study focused on
      87 patients treated for hematological malignancies in services of oncohaematology
      over a period from June 2004 to March 2009. One hundred and twenty-seven
      cytapheresis were conducted to collect the CSP. The rate of CD34+ cells ranged
      from two to 50x10(6) per kilogram. The removal, treatment with 10% DMSO, the
      characterization, cryopreservation, thawing and washing of grafts on Cobe 2991
      were made before the autograft. RESULTS: Forty-nine patients were transplanted
      for multiple myeloma, 24 for Hodgkin's disease, 13 for a non-Hodgkin lymphoma and
      one for rabdomyosarcome. The mean age of patients was 35 years. The mean length
      of hospitalization was 27 days. The average time of release for aplasia is 7 to
      49 days, with a mean of 16 days. A blood transfusion was necessary during the
      aplasia: two to 41 red blood cells per patient and six to 298 platelet units per
      patient. The short-term complications after autologous transplantation are
      primarily infectious. Seven times the progressive hematologic malignancies and
      seven deaths are regrettable. CONCLUSION: The autologous CSP is simple, effective
      and well tolerated, which should be developed in our context.

PMID- 20674440
TI  - [Post-transfusion hepatitis C. From screening to compensation].
AB  - In France, during the last decades preceding the 1990s, 100,000 to 400,000 blood
      recipients may have been infected by hepatitis C. Since 1990, thanks to advances
      in transfusion safety, the risk of hepatitis C contamination has become extremely
      low. Given the natural history of the disease, it can be a long time unnoticed.
      Thus, even today, a significant part of infected individuals do not know their
      serological status. Through several periods and several campaigns, we present the
      various means used for the detection of post-transfusion hepatitis C at the Caen
      University Hospital. These methods have been introduced as a result of
      legislation or through arrangements made by the institution. They were made
      possible through the action of haemovigilance system, monitoring adverse
      reactions related to blood products and of blood products traceability which
      helps to realise special researches in case of suspected transfused blood
      products. In addition to posttransfusion hepatitis C detection, we are discussing
      available victim ways to be indemnified for the injury suffered by contamination
      by hepatitis C.

PMID- 20674441
TI  - [Quality control of defrosted cord blood units: results from an inter-laboratory
      study].
AB  - PURPOSE: Today, haematopoietic stem cell graft from placental blood concerns more
      than 15 % of allogeneic grafts. An inter-laboratory study of the quality control
      of defrosted cord blood units has been coordinated by the French society for cell
      and tissue bioengineering (SFBCT), with the cord blood bank of Bourgogne Franche
      Comte and controlled by the French health products safety agency (Afssaps). The
      aim of this study is to ensure the inter-laboratory reproducibility of the
      quality controls practised by the banks during defrosting. The cellular outputs
      were analyzed according to the defrosting techniques, according to the method
      used in flow cytometry: single-platform (SP) versus double-platform (DP), or the
      product nature, i.e. in total blood or miniaturized. METHODS: Forty-two units of
      placental blood (USP), which were out of range were provided for defrosting to 14
      participating sites. USP were defrosted and controlled according to the
      procedures of each bank. Once the USP is defrosted, a part of the product was
      controlled by the site and the other part by Afssaps. Following controls were
      carried out: numeration of the total nucleated cells (TNC) and of CD34+ cells
      (made by a SP method in Afssaps) and functional assay. RESULTS: Concerning TNC,
      the defrosting sites obtained a cellular output of 94 %+/-28 in day 0 compared
      with an output of 72 %+/-24 in Afssaps showing a rather good stability of the USP
      transmitted with an average deviation of 23 %+/-22. The freezing process with or
      without reduction of volume does not affect this variation. Concerning the
      numeration of CD34+ cells, the average deviation between the participating sites
      and Afssaps was 29 %+/-23 compared with 21 %+/-16 for the sites using a SP method
      against 47 %+/-25 for those using a DP method. The CD34+ outputs are equal to 82
      % +/- 60 in day 0 for the participating sites against 52 %+/-20 for Afssaps. For
      the sites using a DP method, it is stressed that this output is particularly high
      with a rate of 126 %+/-90 (n=15) whereas it is 62 %+/-20 (n=32) for the sites
      using a SP method. CONCLUSION: These results underline a good stability of viable
      CD34+ cells and a greater reliability of the SP methods for the CD34+ cell
      numeration for these defrosted USP. Lastly, the results of the functional assay
      regarding the average clonogenicities (equal to 15 %) reinforce the conclusions
      on the quality of the defrosted products.

PMID- 20674442
TI  - [Evaluation of immediate breast reconstruction and radiotherapy: factors
      associated with complications].
AB  - OBJECTIVES: To determine prospectively the factors associated with reconstruction
      failure (i.e. requiring expander removal) and capsular contracture in patients
      undergoing mastectomy and immediate two-stage breast reconstruction with a tissue
      expander and implant, and radiotherapy for breast cancer. This is a multi
      institutional prospective nonrandomized trial. PATIENTS AND METHODS: Between
      2/1998 and 9/2006, we prospectively evaluated 141 consecutive patients who
      received 141 implants after mastectomy and underwent chest wall radiotherapy (46
      to 50 Gy in 23 to 25 fractions). Patients were evaluated after 24 to 36 months by
      two senior physicians (radiation oncologist and surgeon). RESULTS: Medical follow
      up was 37 months. Baker 1 and 2 capsular contracture was observed in 67.5% of
      patients, Baker 3 and 4 in 32.5%. There were 32 reconstruction failures. In a
      univariate analysis, the following factors were associated with Baker 3 and 4
      capsular contracture: surgeon, use of hormonotherapy and smoking, of which only
      one remained in the multivariate analysis: surgeon. In a univariate analysis, the
      following factors were associated with reconstruction failure: tumor size T3 or
      T4, smoking, pN+ axilla. Three factors remained associated with reconstruction
      failure in a multiple logistic regression: large tumors T3/T4, smoking and pN+
      axilla. CONCLUSIONS: Mastectomy, radiotherapy and immediate breast reconstruction
      with a tissue expander and implant should be considered when breast conserving
      surgery has been denied. Adequate patients can be easily selected by using three
      factors of favourable outcome.

PMID- 20674443
TI  - [Breast cancer in young patient in Morrocco].
AB  - OBJECTIVE: The aim of this retrospective study is to determine the
      epidemiological, clinical, therapeutic aspects and prognostic factors of breast
      cancer in women through a comparative study of 648 patients treated for breast
      cancer: 165 patients are at 35 years of age or less (G 1), 286 patients are more
      than 35 years old and non menopausal (G 2). PATIENT AND METHOD: We have
      collected, for each group, the epidemioclinical data. Nonmetastatic and operable
      cancer was treated by surgery (conservative or radical) followed by an adjuvant
      treatment (chemotherapy, radiotherapy, hormomotherapy) that was indicated
      according to prognosis factors. Locally advanced forms or metastatic at the
      moment of diagnosis were treated firstly by chemotherapy. RESULTS: T2N1 forms
      with lymph node involvement, high grade (SBR II, III) and negative hormonal
      receptors (HR-) were predominant. There was no difference between the two groups
      of women concerning risk factors or clinical criterias, except for the
      mammography that was more sensible in the second group. CONCLUSION: The breast
      cancer in our young patient doesn't seem to be different from the older ones
      either in clinical presentation or evolution. The conclusions of different
      authors are divergent but they are all for evoluated forms with more defavorable
      prognosis than in the older women.

PMID- 20674444
TI  - [Accelerated partial breast irradiation: bifractionated 40Gy in one week. A
      French pilot phase II study].
AB  - PURPOSE: Since 2009, accelerated partial breast irradiation (APBI) in North
      America has been allowed to be used for selected group of patients outside a
      clinical trial according to the ASTRO consensus statement. In France, accelerated
      partial breast irradiation is still considered investigational, several clinical
      trials have been conducted using either intraoperative (Montpellier) or
      Mammosite((r)) (Lille) or brachytherapy modality (PAC GERICO/FNCLCC). Here, we
      report the original dosimetric results of this technique. PATIENTS AND METHODS:
      Since October 2007, Institut Gustave-Roussy has initiated a phase II trial using
      3D-conformal accelerated partial breast irradiation (40 Gy in 10 fractions BID in
      1 week). Twenty-five patients with pT1N0 breast cancer were enrolled and were
      treated by two minitangent photons beams (6MV) and an "en face" electron beam (6
      22 MeV). RESULTS: The mean clinical target volume and planning target volume were
      respectively 15.1cm(3) (range: 5.2-28.7 cm(3)) and 117 cm(3) (range: 52-185
      cm(3)). The planning target volume coverage was adequate with at least a mean of
      99% of the volume encompassed by the isodose 40 Gy. The mean dose to the planning
      target volume was 41.8 Gy (range: 41-42.4 Gy). Dose inhomogeneity did not exceed
      5%. Mean doses to the ipsilateral lung and heart were 1.6 Gy (range: 1.0-2.3 Gy)
      and 1.2 Gy (range: 1.0-1.6 Gy), respectively. CONCLUSION: The 3D conformal
      accelerated partial breast irradiation using two minitangent and "en face"
      electron beams using a total dose of 40 Gy in 10 fractions BID over 5 days
      achieves appropriate planning target volume coverage and offers significant
      normal-tissue sparing (heart, lung). Longer follow-up is needed to evaluate the
      tissue tolerance to this radiation dose.

PMID- 20674445
TI  - [Role of lymph node irradiation in breast cancer patients with negative
      pathologic node status after neoadjuvant chemotherapy: the Rene-Huguenin Cancer
      Center experience].
AB  - PURPOSE: Neoadjuvant chemotherapy generally induces significant changes in the
      pathological extent of disease. This potential down-staging challenges the
      standard indications of adjuvant radiation therapy. We assessed the utility of
      lymph node irradiation in breast cancer patients with pathological N0 status
      (pN0) after neoadjuvant chemotherapy and breast-conserving surgery. PATIENTS AND
      MATERIALS: Among 1054 breast cancer patients treated with neoadjuvant
      chemotherapy in our institution between 1990 and 2004, 248 patients with clinical
      N0 or N1-N2 lymph node status at diagnosis had pN0 status after neoadjuvant
      chemotherapy and breast-conserving surgery. Cox regression analysis was used to
      identify factors influencing locoregional recurrence-free survival, disease-free
      survival and overall survival. RESULTS: All 248 patients received breast
      irradiation, and 158 patients (63.7%) also received lymph node irradiation. With
      a median follow-up of 88 months, the 5-year locoregional recurrence-free survival
      and overall survival rates were respectively 89.4% and 88.7% with lymph node
      irradiation and 86.2% and 92% without lymph node irradiation (no significant
      difference). Survival was poorer among patients who did not have a pathological
      complete primary tumor response (pCR) (hazards ratio [HR]=3.05; 95% CI, 1.17 to
      7.99) and in patients with N1-N2 clinical status at diagnosis ([HR]=2.24; 95% CI,
      1.15 to 4.36). Lymph node irradiation did not significantly affect survival.
      CONCLUSIONS: Relative to combined breast and local lymph node irradiation,
      isolated breast irradiation does not appear to be associated with a higher risk
      of locoregional relapse or death among breast cancer patients with pN0 status
      after neoadjuvant chemotherapy. These results need to be confirmed in a
      prospective study.

PMID- 20674446
TI  - [Health related quality of life and endpoints in oncology].
AB  - In order to perform a clinical trial in oncology, the choice of the primary
      endpoint is a major concern, not only for sample size calculation but also
      regarding the clinical meaning of the results which represents treatment utility
      for patients or public health system. Endpoints could be classified in two
      categories: "clinical endpoints" including overall survival and health related
      quality of life (QoL); "biological markers" including, for example, progression
      free survival (PFS). If conceptual and methodological limits of quality of life
      are well identified with dedicated researches, limits of progression free
      survival remain less targeted and known by clinicians. Numerous clinical trials
      having only demonstrated a progression free survival benefit could be discussed
      according to clinical benefit. In this context, quality of life constitutes an
      available and a useful alternative endpoint for trials to ensure treatment
      benefit in a patient or public health point of view. As quality of life,
      methodological researches should be pursued to improve scientific robustness for
      assessments and analyses of progression free survival.

PMID- 20674447
TI  - [Postoperative radiotherapy of uterine sarcoma: a multicentric retrospective
      study].
AB  - PURPOSE: Surgery is the treatment of choice for localized uterine sarcomas. We
      conducted a retrospective study to define prognostic factors. PATIENTS AND
      METHODS: We studied 111 cases of patients treated by adjuvant radiotherapy for
      uterine sarcoma in seven French centers. The median decline was 31 months. We
      conducted a univariate analysis to identify factors correlated with local
      recurrence. The statistically significant factors were studied in multivariate
      analysis by Cox model. RESULTS: The median dose of external beam radiotherapy was
      45 Gy. Forty-three percent of patients had vaginal vault brachytherapy and 21 %
      chemotherapy. Only 6.3 % of patients had complications of acute grade III and 8.1
      % of long-term sequelae of radiotherapy. The survival rate at 5 years was 74.6 %.
      They noted 12.6 % of isolated locoregional recurrences, against 29.7 % for
      distant recurrences, 80 % were pulmonary. Factors correlated with the risk of
      locoregional relapse were menopausal status (P = 0.045) and surgical margins
      suspicious or not healthy (P = 0.0095). The chemotherapy did not improve overall
      survival or disease free survival but the numbers were low. CONCLUSION: The
      postoperative radiotherapy provides good local control in this disease.
      Brachytherapy is sometimes done, but it does not improve local control.
      Chemotherapy is not a standard localized stage but the rate of metastatic
      recurrence calls for the development of strategies involving systemic treatment
      with radiotherapy.

PMID- 20674448
TI  - [Stereotactic radiotherapy for lung cancer: Non-invasive real-time tumor
      tracking].
AB  - PURPOSE: Stereotactic radiation therapy using the CyberKnife((r)) has been
      introduced in France in 2006. Two treatment modalities are currently available:
      the first one (Synchrony((r))) is a real-time fiducial-based target tracking
      system, while the other (Xsight Lung Tracking [XLT] System((r))) is completely
      fiducial-free. PATIENTS AND METHODS: Sixty-eight patients were treated for a
      pulmonary tumor between June 2007 and November 2009. Since august 2008, the XLT
      System((r)) was used for 26 patients. We report the necessary conditions for the
      XLT System (position, laterality and size of the tumor), the toxicity and outcome
      of this treatment. RESULTS: Twenty-two patients were analyzed. Median follow-up
      was 6 months (min=3; max=16). Local control rate was 100%. The main toxicity was
      grade grade 1 pulmonary alveolitis (27%). No grade 3 or 4 toxicities were
      reported. CONCLUSION: The high local control rate and low toxicity obtained with
      the CyberKnife((r)) XLT System((r)) suggest that such treatment is an alternative
      for inoperable patients.

PMID- 20674449
TI  - [Multifocal Langerhans cell histiocytosis of bone: indications for radiotherapy].
AB  - Langerhans cell histiocytosis is a non-malignant proliferative disease of unknown
      etiology that can affect one or more organs. This is a rare disease, 1 to
      2/100,000, affecting mainly children with a male predominance. The osseous
      lesions are the most frequent (60 to 90%). There is however no consensus
      treatment for the management of these sites. We report the cases of two patients
      successfully treated with radiotherapy after primary chemotherapy, at doses of 15
      Gy in ten sessions of 1.5 Gy for one patient and 18 Gy in ten fractions of 1.8 Gy
      for the other. Single or multifocal bone Langerhans cell histiocytosis without
      visceral involvement is a benign, self-limiting affection in most cases. Some
      bone lesions could be treated by radiotherapy alone. But the high variability of
      doses currently given in the literature does not allow determining the lowest
      effective dose limiting the risk of secondary neoplasia or impaired growth in
      children, in whom lower doses of 6 to 8 Gy are recommended. The decision of
      radiotherapy must be weighed against the risk of the disease. Caution should be
      the rule in this non-malignant tumour pathology.

PMID- 20674450
TI  - The role of radiotherapy in the treatment of pterygium: a review of the
      literature including more than 6000 treated lesions.
AB  - Pterygium is a benign conjunctival neoformation usually treated by surgical
      excision, but recurrences may affect 30% to 89% of cases, so that adjunctive
      therapies like conjunctival autografting, antimitotic drugs and beta-irradiation
      (beta-irradiation) are often used to improve the rate of local control. Our essay
      has reviewed relevant studies addressing the role of postoperative irradiation in
      the treatment of pterygium in the last 30 years through an Internet-based search
      and hand search in libraries. Sixteen studies on beta-irradiation and one on soft
      X-ray irradiation were accessible. They covered more than 6000 lesions treated by
      surgical excision and postoperative beta-irradiation using strontium-90 ((90)Sr)
      applicators at doses varying from 10 to 60 Gy/1-6 fractions/1-6 weeks starting
      within 3 days postoperatively. The rates of local recurrence were in general
      lower than 15% and major complications such as scleral thinning, ulceration,
      infections, or radiation-induced cataract were rarely encountered. Early
      postoperative beta-irradiation at a dose of 30 Gy/three fractions/2-3 weeks
      starting within 24h from surgical excision is an effective and safe procedure
      with local control rates comparable to chemotherapeutic agents and conjunctival
      autografting and superior to simple excision alone.

PMID- 20674452
TI  - Investigations in the physical mechanism of sonocrystallization.
AB  - This paper addresses the issue of mechanistic aspects of sonocrystallization with
      approach of coupling experiments with simulations of bubble dynamics. The major
      experimental result of our study is that, as compared to a mechanically agitated
      crystallization system, the dominant crystal size (or median) of the crystal size
      distribution (CSD) of sonocrystallization systems is smaller, but span of CSD is
      larger. The CSD is influenced by nucleation rate and growth rate. The nature of
      convection in the medium is found to be the crucial factor. In a mechanically
      agitated system, uniform velocity field prevails in crystallization volume, due
      to which both dominant crystal size and span of CSD reduce. The convection in a
      sonicated system is of a different kind. This convection has two components, viz.
      microturbulence (or micro-convection), which is continuous oscillatory motion of
      liquid induced by radial motion of cavitation bubble, and shock waves, which are
      discrete, high pressure amplitude waves emitted by the bubble. These components
      have different impact on crystallization process due to their nature. Shock waves
      increase the nucleation rate and microtubulence governs growth of the nuclei.
      However, the effect of shock waves is more marked than microturbulence (or micro
      convection). Nucleation rate shows an order of magnitude rise with sonication,
      while growth rate (and hence the dominant crystal size) reduces with sonication
      as compared to the mechanically agitated system.

PMID- 20674451
TI  - Fibromyalgia syndrome: prevalence, pharmacological and non-pharmacological
      interventions in outpatient health care. An analysis of statutory health
      insurance data.
AB  - OBJECTIVE: Fibromyalgia syndrome (FMS) is a chronic pain condition impacting on
      quality of life, causing physical and psychological impairment resulting in
      limited participation in professional and social life. The objective of this
      study was to assess the prevalence, recommended pharmacological and non
      pharmacological interventions of FMS, patients' characteristics and to compare
      findings to current research. METHODS: About 1.6 Mio patients of a German
      statutory health insurance company (GEK) in 2007 were analyzed for: (a) the
      prevalence of FMS (ICD-10: M79.7); (b) and comorbid depression (ICD-10: F32/33);
      (c) the recommended pharmacological and non-pharmacological intervention rates;
      (d) and characteristics of patients associated with being prescribed recommended
      interventions. RESULTS: The (a) standardized prevalence of FMS in 2007 was 0.05%
      in men and 0.4% in women. (b) 51.9% of the patients with prevalent FMS had a
      comorbid depression in 2007 (88.2% female). (c) 66% of FMS patients received the
      recommended pharmacological treatment, 59% physical therapy, 6.1% cognitive
      behavioural therapy and 3.4% a combination of these (multi-component therapy,
      MCT). (d) One year increase in age was associated with a 3% decrease in the
      predicted odds of receiving MCT (95%, CI 0.95-0.99). CONCLUSION: The current data
      indicate an FMS-prevalence that differs from epidemiological surveys and
      screenings, probably due to methodological differences. Especially females with
      comorbid depression are affected. The likelihood of receiving MCT is not
      associated with gender, but with younger age. Yet, the findings seem to indicate
      insufficient and inadequate treatment, but FMS warrants more research.

PMID- 20674453
TI  - Improvement of iron removal from silica sand using ultrasound-assisted oxalic
      acid.
AB  - This paper deals with the removal of iron from silica sand in aqueous oxalic
      acid, in the absence and presence of ultrasound. The parameters investigated were
      the reaction temperature, stirring speed, ultrasound power, acid concentration
      and reaction time. The optimum conditions for the maximum removal of 75.4% of
      iron with ultrasound were determined as follows: reaction temperature, 95 degrees
      C; stirring speed, 500 rpm; ultrasound power, 150 W; acid concentration, 4 g/l;
      reaction time 30 min. The method induces a remarkable acceleration for the iron
      leaching process, the leach acid concentration reducing dramatically and the
      removal efficiency increasing considerably, compared to conventional stirring
      method. The advantages of ultrasound-assisted leaching were also confirmed by
      characterizing the silica sand and the leached solid samples using particle size,
      SEM and color measurement analysis.

PMID- 20674454
TI  - Fluid transfer as a mechanism leading to endotension.
AB  - Some abdominal aortic aneurysms bridged with a minimally invasively introduced
      stent graft prosthesis increase in size without any diagnosable evidence of
      endoleakage (endotension). There are three possible pathways proposed through
      which undetectable low rates of blood flow may cause an aneurysm sac to be
      refilled: through the thrombus at the prosthesis attachment sites, through the
      clotted collaterals and through the clotted stent graft wall. If the inflow is
      more rapid than any drainage through the wall of the aneurysm is re-pressurised.
      However, critical magnitudes for the permeability of the clotted graft and the
      geometry of the thrombus at the aneurysm, necessary to inhibit endotension, are
      not known. The aim of this study was to determine which boundary conditions
      prevent endotension. An analytical model based on Darcy's Law was used to
      estimate the pressure in the aneurysm sac due to fluid transfer. Experimentally
      determined time- and pressure-dependent permeability of red and intraluminal
      thrombus, and of clotted graft materials were input into the model. The
      computational analysis showed that endotension is unlikely to be caused by fluid
      transfer from the collaterals or via the prosthesis attachment sites, but rather
      due to flow through the stent graft wall. Based on this study it can be stated
      that grafts with a permeability below 2e-13 mm(2) should diminish the occurrence
      of endotension.

PMID- 20674455
TI  - Automatic breath and snore sounds classification from tracheal and ambient sounds
      recordings.
AB  - In this study respiratory sound signals were recorded from 23 patients suspect of
      obstructive sleep apnea, who were referred for the full-night sleep lab study.
      The sounds were recorded with two microphones simultaneously: one placed over
      trachea and one hung in the air in the vicinity of the patient. During recording
      the sound signals, patients' Polysomnography (PSG) data were also recorded
      simultaneously. An automatic method was developed to classify breath and snore
      sound segments based on their energy, zero crossing rate and formants of the
      sound signals. For every sound segment, the number of zero crossings, logarithm
      of the signal's energy and the first formant were calculated. Fischer Linear
      Discriminant was implemented to transform the 3-dimensional (3D) feature set to a
      1-dimensional (1D) space and the Bayesian threshold was applied on the
      transformed features to classify the sound segments into either snore or breath
      classes. Three sets of experiments were implemented to investigate the method's
      performance for different training and test data sets extracted from different
      neck positions. The overall accuracy of all experiments for tracheal recordings
      were found to be more than 90% in classifying breath and snore sounds segments
      regardless of the neck position. This implies the method's accuracy is
      insensitive to patient's position; hence, simplifying data analysis for an entire
      night recording. The classification was also performed on sounds signals recorded
      simultaneously with an ambient microphone and the results were compared with
      those of the tracheal recording.

PMID- 20674456
TI  - Influence of mesh density, cortical thickness and material properties on human
      rib fracture prediction.
AB  - The purpose of this paper was to investigate the sensitivity of the structural
      responses and bone fractures of the ribs to mesh density, cortical thickness, and
      material properties so as to provide guidelines for the development of finite
      element (FE) thorax models used in impact biomechanics. Subject-specific FE
      models of the second, fourth, sixth and tenth ribs were developed to reproduce
      dynamic failure experiments. Sensitivity studies were then conducted to quantify
      the effects of variations in mesh density, cortical thickness, and material
      parameters on the model-predicted reaction force-displacement relationship,
      cortical strains, and bone fracture locations for all four ribs. Overall, it was
      demonstrated that rib FE models consisting of 2000-3000 trabecular hexahedral
      elements (weighted element length 2-3mm) and associated quadrilateral cortical
      shell elements with variable thickness more closely predicted the rib structural
      responses and bone fracture force-failure displacement relationships observed in
      the experiments (except the fracture locations), compared to models with constant
      cortical thickness. Further increases in mesh density increased computational
      cost but did not markedly improve model predictions. A +/-30% change in the major
      material parameters of cortical bone lead to a -16.7 to 33.3% change in fracture
      displacement and -22.5 to +19.1% change in the fracture force. The results in
      this study suggest that human rib structural responses can be modeled in an
      accurate and computationally efficient way using (a) a coarse mesh of 2000-3000
      solid elements, (b) cortical shells elements with variable thickness distribution
      and (c) a rate-dependent elastic-plastic material model.

PMID- 20674457
TI  - Fracture toughness and compressive properties of cancellous bone at the head of
      the femur and relationships to non-invasive skeletal assessment measurements.
AB  - Osteoporosis defines a causal relationship between reduced bone density, reduced
      mechanical competence of the bone tissue of the sufferers and concomitantly an
      increased risk of fracture in life. The aims of the present study is: (1) to
      provide further evidence to support the use of Quantitative Ultrasound (QUS)
      results from peripheral sites to provide a prediction of the density of the
      proximal femur; and (2) to provide rational evidence for the well-proven ability
      of QUS to predict directly 'risk of fracture'. 20 femoral heads were obtained
      from 15 Caucasian females and 5 Caucasian males undergoing emergency surgery for
      a fractured neck of femur. QUS investigations of the calcaneus, proximal phalanx,
      distal radius and mid-shaft tibia were undertaken on the donors with 72h of
      surgery. 128 fracture toughness samples and 20 compression cores were
      manufactured and tested. Significant relationships were found between QUS
      parameters determined in vivo and the apparent density (g/cm(3)) of the tissue at
      the proximal femur and both the fracture toughness and strength determined in
      vitro from the same donor individual. In this study we relate QUS results
      obtained in vivo to the actual apparent density of bone tissue from the proximal
      femur, donated by the same individual, and the fracture toughness and compressive
      strength. The study demonstrates the ability of QUS investigations at peripheral
      sites to accurately predict the density of bone from the proximal femur and
      provides evidence to support the use of QUS to predict the 'risk of fracture'
      directly.

PMID- 20674458
TI  - Time-dependent fixation and implantation forces for a femoral knee component--an
      in vitro study.
AB  - Implant survival rate is a primary concern for individuals receiving a primary
      total knee arthroplasty. Loosening is the primary reason for revision surgery and
      was therefore the focus of the current study. To better understand the mechanics
      of implant fixation, the time-dependent fixation of a femoral knee component was
      measured in vitro on three cadaveric femurs. The fixation of each femoral knee
      component was measured with strain gauged implants for at least 10min on each
      femoral component. Additionally, impaction forces were measured during the
      implantation of each component. These forces were 2-6 times less than previously
      reported. The implantation impact forces were higher for the bones with higher
      bone density. Power law regressions were fit to the absolute value of the
      principal strains measured on the components over time to quantify the relaxation
      of the bone. The average power coefficient value for the three bones was lower
      for the bones with higher bone density. The average power coefficient value for
      the maximum principal strains was significantly higher than that of the minimum
      principal strains in each bone. The results were extrapolated to approximate the
      fixation strength at 9 months after implantation. In this time period the strain
      was predicted to decrease to between 78 and 91% of the strain 1s after
      implantation where those with lower bone density will have decreased fixation
      strength.

PMID- 20674459
TI  - Respiratory problems in neurologic movement disorders.
AB  - BACKGROUND: Movement disorders are a group of neurological motor disturbances
      manifested by either paucity or slowness of movement, such as seen in Parkinson's
      disease, or by abnormal involuntary movements, called hyperkinesias, which
      include tremor, dystonia, chorea, tics, myoclonus, and stereotypy. The aim of
      this review is to draw attention to the respiratory problems that are sometimes
      associated with these various movement disorders. METHODS: References for this
      review were identified by searches of PubMed through June 2010, a text word
      search strategy. There were no language restrictions. Books on movement
      disorders, personal experience and judgment were also used in preparation of this
      review. RESULTS: Data from 245 articles were critically reviewed, compared and
      integrated. CONCLUSION: Although movement disorders are primarily considered
      motor disorders, the purpose of this review is to draw attention to their
      involvement of the respiratory system. It is critical that clinicians recognize
      the phenomenology and take appropriate action to prevent and treat the various
      respiratory problems associated with the various neurological disorders. Timely
      institution of therapeutic interventions is needed to favorably impact on the
      quality of life and survival of these patients.

PMID- 20674461
TI  - Apolipoprotein E epsilon 4 allele is not associated with age at onset or MMSE of
      Parkinson's disease in a Korean study.

PMID- 20674460
TI  - Occurrence of depression and anxiety prior to Parkinson's disease.
AB  - OBJECTIVE: To assess the relationship between depression and anxiety and
      Parkinson's disease (PD). BACKGROUND: Many people with PD suffer from depression
      and anxiety prior to the onset of motor symptoms. Studies suggest these
      psychiatric conditions may be risk factors for PD or prodromal non-motor
      symptoms. METHODS: Using a population-based approach in three California
      counties, we recruited 371 incident PD cases, 402 population and 115 sibling
      controls. We recorded self-reports of lifetime depression/anxiety diagnoses and
      use of psychotropic medications. We adjusted for age, race, sex, pack-years of
      smoking, and education, and also conducted analyses after excluding (lagging)
      both diagnoses and medication use first occurring within 2, 5, 10, and 20 years
      of the index/diagnosis date. RESULTS: Cases were more likely to have received a
      diagnosis of depression or anxiety at any time prior to index date (OR 1.42, 95%
      CI 1.01, 2.00), but were not more likely to have been both diagnosed and treated
      (OR 1.11, 95% CI 0.77, 1.60). Male PD patients received diagnoses combined with
      treatment more often than population controls within 5 years of PD diagnosis (OR
      2.21, 95% CI 1.21, 4.04; 2 year lag: OR 2.44, 95% CI 1.29, 4.61; 5 year lag: OR
      1.67, 95% CI 0.80, 3.49). We did not see any differences for females. Results for
      cases compared to sibling controls were similar to those for population controls.
      CONCLUSION: These results suggest that depression and anxiety may be early
      symptoms during the prodromal phase of PD.

PMID- 20674462
TI  - The prevalence of Parkinson's disease in a rural area of North-East England.
AB  - AIMS AND OBJECTIVES: We have previously reported the age-adjusted prevalence of
      idiopathic Parkinson's disease (PD) in North Tyneside, an urban area of North
      East England, as 139 cases (95% CI 116 to 162) per 100,000. The aim of this study
      was to report the prevalence of idiopathic PD in a rural area of North-East
      England. METHODS: The same case-finding methodology as that employed in North
      Tyneside was used to identify cases of PD in an area of North Northumberland with
      a population of 59,613 at the 2001 UK census. All GPs in the study area were
      asked to provide details of patients registered with their service that may have
      PD or were on PD medication. Furthermore, all patients registered with the local
      PD service or under the care of a consultant neurologist or other relevant
      secondary care specialist were considered for inclusion. Inclusion in the study
      required fulfillment of the UK Brain Bank criteria. RESULTS: One-hundred-and-six
      cases were identified (50 women and 56 men), giving crude and age-adjusted
      prevalence estimates of 178 cases (95% CI 144 to 212) and 142 cases (95% CI 118
      to 165) per 100,000 respectively. The age-adjusted prevalence rate within our
      rural study area was remarkably similar to that seen in other urban UK studies.
      Only 71 cases (67.0%) were identified through GP records. CONCLUSIONS: The
      prevalence of PD rural and urban areas of North-East England is remarkably
      similar.

PMID- 20674463
TI  - Evidence from cognitive neuroscience supports action observation as part of an
      integrated approach to stroke rehabilitation.

PMID- 20674465
TI  - MYB transcription factors in Arabidopsis.
AB  - The MYB family of proteins is large, functionally diverse and represented in all
      eukaryotes. Most MYB proteins function as transcription factors with varying
      numbers of MYB domain repeats conferring their ability to bind DNA. In plants,
      the MYB family has selectively expanded, particularly through the large family of
      R2R3-MYB. Members of this family function in a variety of plant-specific
      processes, as evidenced by their extensive functional characterization in
      Arabidopsis (Arabidopsis thaliana). MYB proteins are key factors in regulatory
      networks controlling development, metabolism and responses to biotic and abiotic
      stresses. The elucidation of MYB protein function and regulation that is possible
      in Arabidopsis will provide the foundation for predicting the contributions of
      MYB proteins to the biology of plants in general.

PMID- 20674466
TI  - Quantifying variability in radiation dose due to respiratory-induced tumor
      motion.
AB  - State of the art radiation treatment methods such as hypo-fractionated
      stereotactic body radiation therapy (SBRT) can successfully destroy tumor cells
      and avoid damaging healthy tissue by delivering high-level radiation dose that
      precisely conforms to the tumor shape. Though these methods work well for
      stationary tumors, SBRT dose delivery is particularly susceptible to organ
      motion, and few techniques capable of resolving and compensating for respiratory
      induced organ motion have reached clinical practice. The current treatment
      pipeline cannot accurately predict nor account for respiratory-induced motion in
      the abdomen that may result in significant displacement of target lesions during
      the breathing cycle. Sensitivity of dose deposition to respiratory-induced organ
      motion represents a significant challenge and may account for observed
      discrepancies between predictive treatment plan indicators and clinical patient
      outcomes. Improved treatment-planning and delivery of SBRT requires an accurate
      prediction of dose deposition uncertainties resulting from respiratory motion. To
      accomplish this goal, we developed a framework that models both organ
      displacement in response to respiration and the underlying random variations in
      patient-specific breathing patterns. Our organ deformation model is a four
      dimensional maximum a posteriori (MAP) estimation of tissue deformation as a
      function of chest wall amplitudes computed from clinically obtained respiratory
      correlated computed tomography (RCCT) images. We characterize patient-specific
      respiration as the probability density function (PDF) of chest wall amplitudes
      and model patient breathing patterns as a random process. We then combine the
      patient-specific organ motion and stochastic breathing models to calculate the
      resulting variability in radiation dose accumulation. This process allows us to
      predict uncertainties in dose delivery in the presence of organ motion and
      identify tissues at risk of receiving insufficient or harmful levels of
      radiation.

PMID- 20674467
TI  - Can social interaction constitute social cognition?
AB  - An important shift is taking place in social cognition research, away from a
      focus on the individual mind and toward embodied and participatory aspects of
      social understanding. Empirical results already imply that social cognition is
      not reducible to the workings of individual cognitive mechanisms. To galvanize
      this interactive turn, we provide an operational definition of social interaction
      and distinguish the different explanatory roles - contextual, enabling and
      constitutive - it can play in social cognition. We show that interactive
      processes are more than a context for social cognition: they can complement and
      even replace individual mechanisms. This new explanatory power of social
      interaction can push the field forward by expanding the possibilities of
      scientific explanation beyond the individual.

PMID- 20674464
TI  - BMP signaling in vascular development and disease.
AB  - Genetic and functional studies indicate that common components of the bone
      morphogenetic protein (BMP) signaling pathway play critical roles in regulating
      vascular development in the embryo and in promoting vascular homeostasis and
      disease in the adult. However, discrepancies between in vitro and in vivo
      findings and distinct functional properties of the BMP signaling pathway in
      different vascular beds, have led to controversies in the field that have been
      difficult to reconcile. This review attempts to clarify some of these issues by
      providing an up to date overview of the biology and genetics of BMP signaling
      relevant to the intact vasculature.

PMID- 20674468
TI  - The effect of soft contact lens care products on lens modulus.
AB  - PURPOSE: To examine the relative changes in modulus of nine soft contact lens
      materials when exposed to three lens care solutions. METHOD: Measurements of
      elastic modulus were made using an Instron 3343 tensiometer of lenses which had
      been pre-soaked in ReNu Multi-Purpose (Bausch & Lomb), OPTI-FREE RepleniSH
      (Alcon), Clear Care (CIBA Vision) hydrogen peroxide, or a saline control solution
      for one week. The solutions were changed three times during the week-long soaking
      period. Following this, the lenses were measured for centre thickness and were
      cut into two samples of identical width. Young's modulus was measured in the
      force range of 0.015-0.035 N. RESULTS: Measurements in saline ranged form 0.31MPa
      for etafilcon A to 1.76 MPa for lotrafilcon A. All of the lenses, with the
      exception of senofilcon A, displayed a significant change in modulus with at
      least one of the solutions. Both etafilcon A and lotrafilcon B showed a
      significant change in modulus with all solutions. With lotrafilcon B in hydrogen
      peroxide solution, modulus reduced from 1.32 to 0.93 MPa (P<0.0001). Galyfilcon A
      decreased from 0.36 to 0.31 MPa in ReNu Multi-Purpose (P<0.0001) and lotrafilcon
      A decreased from 1.76 to 1.64 MPa in OPTI-FREE RepleniSH (P=0.04). Comfilcon A
      increased from 0.78 to 0.85 MPa (P<0.0001) in peroxide. CONCLUSIONS: The use of
      some contact lens-solution combinations results in significant changes in
      modulus. In the case of the multi-purpose solutions, the changes probably relate
      to uptake of the formulation components and, in the case of peroxide, to chemical
      changes to the polymer.

PMID- 20674469
TI  - Obituary--rigid contact lenses.
AB  - Scleral and corneal rigid lenses represented 100 per cent of the contact lens
      market immediately prior to the invention of soft lenses in the mid-1960s. In the
      United Kingdom today, rigid lenses comprise 2 per cent of all new lens fits. Low
      rates of rigid lens fitting are also apparent in 27 other countries which have
      recently been surveyed. Thus, the 1998 prediction of the author that rigid lenses
      -also referred to as 'rigid gas permeable' (RGP) lenses or 'gas permeable' (GP)
      lenses--would be obsolete by the year 2010 has essentially turned out to be
      correct. In this obituary, the author offers 10 reasons for the demise of rigid
      lens fitting: initial rigid lens discomfort; intractable rigid lens-induced
      corneal and lid pathology; extensive soft lens advertising; superior soft lens
      fitting logistics; lack of rigid lens training opportunities; redundancy of the
      rigid lens 'problem solver' function; improved soft toric and bifocal/varifocal
      lenses; limited uptake of orthokeratology; lack of investment in rigid lenses;
      and the emergence of aberration control soft lenses. Rigid lenses are now being
      fitted by a minority of practitioners with specialist skills/training. Certainly,
      rigid lenses can no longer be considered as a mainstream form of contact lens
      correction. May their dear souls (bulk properties) rest in peace.

PMID- 20674470
TI  - Development of antibody surrogates for the treatment of cancers and autoimmune
      disease.
AB  - Some therapeutic monoclonal antibodies function by focusing the killing power of
      the immune system on particular cellular targets, a process known as antibody
      dependent cell-mediated cytotoxicity (ADCC). There is considerable interest in
      developing small-molecule therapeutics that utilize this mechanism of action and
      so act as a kind of antibody surrogate. Progress and challenges in this
      interesting field are reviewed here.

PMID- 20674471
TI  - Synthetic receptors with antibody-like binding affinities.
AB  - Antibodies are critical reagents in biological research and are increasingly
      being developed as therapeutic agents. They typically exhibit very high affinity
      and selectivity for their ligands. Synthetic protein-binding agents rarely
      achieve the combination of high affinity and selectivity for their target protein
      that is typical of a good antibody. However, significant efforts are underway to
      develop a new generation of protein ligands with improved properties. This
      article reviews progress towards this goal and suggests fruitful strategies for
      future research.

PMID- 20674472
TI  - Let's get digital: digitizing chemical biology with microfluidics.
AB  - Digital microfluidics (DMF) has recently emerged as a popular technology for a
      wide range of applications in chemical biology. In DMF, nL-mL droplets containing
      samples and reagents are controlled (i.e., moved, merged, mixed, and dispensed
      from reservoirs) by applying a series of electrical potentials to an array of
      electrodes coated with a hydrophobic insulator. DMF is distinct from microchannel
      based fluidics as it allows for precise control over multiple reagent phases
      (liquid and solid) in heterogeneous systems with no need for complex networks of
      microvalves. Here, we review the state-of-the-art in DMF as applied to a wide
      range of applications in chemical biology, including proteomics, enzyme assays
      and immunoassays, applications involving DNA, cell-based assays, and clinical
      applications.

PMID- 20674473
TI  - Nanoscale interfaces to biology.
AB  - Nanotechnology has held great promise for revolutionizing biology. The biological
      behavior of nanomaterials depends primarily on how they interface to biomolecules
      and their surroundings. Unfortunately, interface issues like non-specific
      adsorption are still the biggest obstacles to the success of nanobiotechnology
      and nanomedicine, and have held back widespread practical use of nanotechnology
      in biology. Not only does the biological interface of nanoparticles (NPs) need to
      be understood and controlled, but also NPs must be treated as biological entities
      rather than inorganic ones. Furthermore, one can adopt an engineering perspective
      of the NP-biological interface, realizing that it has unique, exploitable
      properties.

PMID- 20674474
TI  - White light generation in Eu- and Mn-codoped Ca(7)Mg(2)P(6)O(24) phosphor for
      white light-emitting diodes.
AB  - Polycrystalline Ca(7)Mg(2)P(6)O(24):Eu(2+),Mn(2+) phosphors were prepared by a
      solid-state reaction under a weak reductive atmosphere. The phosphors have been
      characterized by X-ray diffraction and fluorescence measurements. The results
      show that the obtained phosphors are of single-phase rhombohedral
      Ca(7)Mg(2)P(6)O(24). Upon excitation of 355nm ultraviolet (UV) light, two intense
      broad bands have clearly been observed due to the allowed 5d-4f transition of
      Eu(2+) and the forbidden (4)T(1)-(6)A(1) transition of Mn(2+), respectively. A
      white light has been obtained from Ca(7)Mg(2)P(6)O(24):0.035Eu(2+),0.5Mn(2+)
      phosphor with CIE chromaticity coordinates of (x=0.32, y=0.29) and color
      temperature of 6175K. These results suggest that
      Ca(7)Mg(2)P(6)O(24):Eu(2+),Mn(2+) phosphors could be a promising candidate for UV
      converting white light-emitting diodes (LEDs).

PMID- 20674475
TI  - Synthesis, spectroscopic characterization and reactivity studies of
      oxovanadium(IV) complexes with bulky N,N'-polymethylenebis(3,5
      (t)Bu(2)salicylaldimine) ligands.
AB  - A series of new sterically hindered N,N'-polymethylenebis(3,5
      (t)Bu(2)salicylaldimine) ligands (H(2)L(x)) VO(IV) complexes, [VO{(2-O-3,5
      (t)Bu(2)C(6)H(2))CHN-R-NCH-(3,5-(t)Bu(2)-C(6)H(2)O-2)] (X), where R=-(CH(2))(3)-
      (3), -(CH(2))(4)- (4), -(CH(2))(5)- (5), -(CH(2))(6)- (6) and 
      CH(2)C(CH(3))(2)CH(2)- (7) and early reported -(CH(2))(2)- (1) and 
      CH(2)CH(CH(3))- (2), has been synthesized and characterized by spectroscopic (IR,
      UV/vis, (1)H NMR, EPR), electrochemical and magnetic susceptibility measurements.
      Complexes 1-7 are described a trigonal distorted pyramids. All seven compounds
      give nearly the same parallel hyperfine coupling constant (A(z)) regardless that
      the geometry of VO(IV) changes from square pyramidal to trigonal distorted
      pyramids. Chemical oxidation of 1-7 by one equiv Ce(IV) leads to the formation of
      stable [VO(V)L(x)](+) complexes. Cyclic voltammograms of 2-6 in DMSO along with a
      quasi-reversible VO(IV)/VO(V) redox couple also showed irreversible
      phenolate/phenoxyl responses. Each 1 and 7 shows only one reversible VO(IV)
      centered oxidation waves. Chemical oxidation of H(2)L(x) forms the stable
      [H(2)L(x)](+) radical species.

PMID- 20674476
TI  - Diagnostic accuracy of an allele-specific reverse transcriptase-PCR assay
      targeting the H275Y oseltamivir resistant mutation in 2009 pandemic influenza
      A/H1N1 virus.
AB  - BACKGROUND: Oseltamivir resistant 2009 pandemic influenza A/H1N1 viruses (pH1N1)
      are emerging and rapid molecular assays identifying these strains are needed for
      clinical management. OBJECTIVE: Development and evaluation of an allele-specific,
      real-time reverse transcriptase-PCR assay (ASPCR) targeting the H275Y oseltamivir
      resistant mutation in pH1N1 virus. STUDY DESIGN: ASPCR uses two allele-specific
      forward primers (wild-type and mutant) and a common reverse primer and probe.
      Wild-type and mutant genotypes were defined by the difference in PCR Ct values
      (DeltaCt(mut-wt)) between the mutant primer and wild-type primer amplification
      curves for the same sample. Mixtures of wild-type and mutant genotypes were
      analyzed to evaluate sensitivity and determine assay cut-off values. ASPCR
      results were confirmed using an allelic discrimination assay (AD) and
      pyrosequencing. RESULTS: Mixtures containing 5-95% mutant genotype could be
      detected. A DeltaCt(mut-wt)>or=3.5 identified wild-type genotype (<10% mutant);
      between 3.5 and -3.5 identified mixed genotypes (10-90% mutant); and <or=-3.5
      identified fully mutant genotype (>90% mutant). Among 264 clinical samples, 171
      were wild-type, 10 were mixed, and 29 were fully mutant. The 39 samples with
      mixed or mutant results were from 11 patients. Of 107 samples with sufficient
      volume tested by ASPCR and AD, 12 were indeterminate by AD due to low viral load,
      86 were wild-type by both assays, and 9 were mutant by both assays. Thirteen
      samples were confirmed by pyrosequencing and one discrepant sample was mixed by
      ASPCR and fully mutant by pyrosequencing. CONCLUSIONS: ASPCR is sensitive,
      quantitative and specific for H275Y mutation analysis and provides an accurate
      approach for detecting pH1N1 oseltamivir resistance in clinical samples.

PMID- 20674477
TI  - Antiviral agents: to treat or not to treat? An old dilemma revisited in light of
      new data from the 2009 influenza A(H1N1) pandemic.

PMID- 20674478
TI  - Evaluation of the Xpert Flu A Panel nucleic acid amplification-based point-of
      care test for influenza A virus detection and pandemic H1 subtyping.
AB  - BACKGROUND: Influenza antigenic point-of-care (POC) tests are too insensitive for
      individual reliable diagnosis of influenza virus infections without additional
      laboratory confirmation. Molecular POC tests could be a valuable alternative.
      OBJECTIVES: To evaluate the first influenza molecular POC test commercially
      available, the Cepheid Xpert Flu A Panel designed to simultaneously detect
      influenza A virus and subtype A(H1N1) 2009 pandemic virus, and compare it with in
      house real-time RT-PCR (qRT-PCR). STUDY DESIGN: Clinical specimens positive for
      influenza virus and influenza virus isolates with different viral loads and of
      different type and subtype were used to determine the analytical reactivity and
      sensitivity. A panel of pathogen negative specimens and isolates of 19 different
      respiratory pathogens were used to determine the analytical specificity. RESULTS:
      Except A(H9N2) virus the Xpert Flu A Panel detected A(H1N1) seasonal and 2009
      pandemic, A(H3N2), A(H5N2), A(H5N1) and A(H7N7) viruses and correctly subtyped
      A(H1N1) 2009 virus. Analytical sensitivity was similar to qRT-PCR in the range of
      400-5000 viral particles per ml. However, of most subtypes some specimens with
      cycle threshold values greater than 30 in qRT-PCR and A(H1N1) 2009 specimens with
      inconsistent results in the qRT-PCR due to primer or probe mismatches were not
      detected in the Xpert Flu A Panel. Analytical specificity was 100%. CONCLUSIONS:
      The Xpert Flu A Panel is the first commercially available POC molecular test for
      detection of influenza A virus and determination of the H1 2009 subtype and is
      analytically reasonable sensitive compared with qRT-PCR and highly specific and
      therefore a welcome alternative to antigenic POC tests.

PMID- 20674479
TI  - Chikungunya fever in Singapore: acute clinical and laboratory features, and
      factors associated with persistent arthralgia.
AB  - BACKGROUND: In Singapore, the first local outbreak of chikungunya was reported in
      January 2008, followed by a larger outbreak occurred in August 2008. During the
      initial outbreak period, a strict containment strategy was adopted and all
      chikungunya PCR-confirmed cases were isolated and hospitalised at the designated
      national outbreak management centre. OBJECTIVES: To detail daily clinical and
      laboratory features of chikungunya cases during acute illness, and determine
      factors associated with persistent arthralgia at week 6. STUDY DESIGN:
      Prospective cohort study of patients with PCR-confirmed chikungunya infection and
      hospitalised within 5 days of illness onset, from 1st August to 10th November
      2008. Post-hospital discharge, patients were followed up at the specialist
      outpatient clinic, and assessed for arthralgia at week 6 of illness. RESULTS: Of
      the 97 patients in the study, the most common presenting symptoms were fever
      (89.7%) and arthralgia (87.6%). Mean nadir leukocyte and platelet counts were
      3.5(SD 1.9) * 10(9)/L and 165(SD 42) * 10(9)/L respectively. Of the 39 patients
      who were evaluated at week 6, 14 (35.9%) had persistent arthralgia. Those with
      persistent arthralgia tended to be females (p = 0.003), and had a lower peak
      creatinine level (p = 0.036) than those without. Peak viral load (p = 0.664), and
      duration of fever (p = 0.056) and viremia (p = 0.55) respectively, were not
      significantly different between those with persistent arthralgia and those
      without. CONCLUSIONS: This study details the daily clinical and laboratory
      features of chikungunya patients during acute illness. Those with persistent
      arthralgia tended to be females, who had significantly lower peak creatinine
      level.

PMID- 20674480
TI  - Effect of breathing 7% carbon dioxide on the human soleus Hoffmann-reflex
      recruitment curve.
AB  - OBJECTIVE: To examine the effect of inhaling 7% carbon dioxide on the recruitment
      curve of the soleus H-reflex. METHODS: Five males and five females (apparently
      healthy; 21-40 yr) with surface EMG electrodes over the soleus muscle randomly
      breathed room air or a 7% CO2, 21% O2, balance N2 mix for 10 min. The tibial
      nerve was stimulated to elicit the H-reflex recruitment curve. H-reflex
      threshold, motor threshold, slope of ascending H-reflex curve, Hmax:Mmax ratio,
      and latency of Hmax were compared. RESULTS: Breathing 7% carbon dioxide increased
      the H-reflex threshold (as a percent of motor threshold) from 73% (SD 0.09) to
      84% (SD 0.12; p<0.05), decreased the Hmax:Mmax ratio from 0.504 (SD 0.290) to
      0.403 (SD 0.253; p<0.05), and increased the H wave latency (in msec) from 32.8
      (SD 1.6) to 34.6 (SD 2.6; p<0.05). Slope of ascending H-reflex curve (room air:
      125 (SD 89); CO2: 135 (SD 92); p>0.05), Mmax (room air: 3.70 mV (SD 1.57); CO2:
      3.69 mV (SD 1.53); p>0.05), and motor threshold (p>0.05) remained unchanged.
      CONCLUSIONS: Breathing 7% carbon dioxide reduces afferent synaptic transmission
      in the soleus muscle by slowing transmission, increasing threshold stimulus, and
      reducing H wave size. SIGNIFICANCE: Clinicians and scientists should consider the
      possibility that carbon dioxide can reduce afferent synaptic transmission.

PMID- 20674481
TI  - Is there a time window for increased plasticity? The need for longitudinal data.

PMID- 20674482
TI  - Detection of experimental ERP effects in combined EEG-fMRI: evaluating the
      benefits of interleaved acquisition and independent component analysis.
AB  - OBJECTIVE: The present study examined the benefit of rapid alternation of EEG and
      fMRI (a common strategy for avoiding artifact caused by rapid switching of MRI
      gradients) for detecting experimental modulations of ERPs in combined EEG-fMRI.
      The study also assessed the advantages of aiding the extraction of specific ERP
      components by means of signal decomposition using Independent Component Analysis
      (ICA). METHODS: 'Go-nogo' task stimuli were presented either during fMRI scanning
      or in the gaps between fMRI scans, resulting in 'gradient' and 'no-gradient'
      ERPs. 'Go-nogo' differences in the N2 and P3 components were subjected to
      conventional ERP analysis, as well as single-trial and reliability analyses.
      RESULTS: Comparable N2 and P3 enhancement on 'nogo' trials was found in the
      'gradient' and 'no-gradient' ERPs. ICA-based signal decomposition resulted in
      better validity (as indicated by topography), greater stability and lower
      measurement error of the predicted ERP effects. CONCLUSIONS: While there was
      little or no benefit of acquiring ERPs in the gaps between fMRI scans, ICA
      decomposition did improve the detection of experimental ERP modulations.
      SIGNIFICANCE: Simultaneous and continuous EEG-fMRI acquisition is preferable to
      interleaved protocols. ICA-based decomposition is useful not only for artifact
      cancellation, but also for the extraction of specific ERP components.

PMID- 20674483
TI  - Rolandic discharges: clinico-neurophysiological correlation.
AB  - OBJECTIVE: The aim of this study was to analyze neurophysiologic aspects of
      rolandic discharges. METHODS: We reviewed 45 electroencephalograms of patients
      divided into two groups: those with benign childhood epilepsy with centrotemporal
      spikes (BCECTS) and symptomatic partial epilepsy (SPE), following ILAE criteria
      (1989). The EEG data analyzed were: horizontal dipole discharges, double spike
      phenomenon, the extension of epileptiform discharges and background activity.
      RESULTS: There was a predominance of horizontal dipole between patients with
      BCECTS compared with patients with SPE; however, this difference was not
      statistically significant. There was also no statistically significant difference
      between the two groups when the double spike phenomenon and the extension of
      discharges beyond the rolandic area were considered. The slower background
      activity in the SPE group was the only variable with statistical significance.
      CONCLUSIONS: This study revealed similarities between rolandic discharges of two
      different epilepsy groups. The only reliable parameter to differentiate the
      groups was the background activity. SIGNIFICANCE: Our findings suggest that most
      EEG rolandic features are not pathognomonic of BCECTS, as they are related to the
      area of the discharges and not to the epileptic syndrome itself.

PMID- 20674484
TI  - "New Year's resolutions" versus real life.

PMID- 20674485
TI  - Predicting the future: ERP markers of language risk in infancy.

PMID- 20674486
TI  - The onset of ALS?

PMID- 20674487
TI  - Two-stage electrodialytic concentration of glyceric acid from fermentation broth.
AB  - The aim of this research was the application of a two-stage electrodialysis (ED)
      method for glyceric acid (GA) recovery from fermentation broth. First, by
      desalting ED, glycerate solutions (counterpart is Na+) were concentrated using
      ion-exchange membranes, and the glycerate recovery and energy consumption became
      more efficient with increasing the initial glycerate concentration (30 to 130
      g/l). Second, by water-splitting ED, the concentrated glycerate was
      electroconverted to GA using bipolar membranes. Using a culture broth of
      Acetobacter tropicalis containing 68.6 g/l of D-glycerate, a final D-GA
      concentration of 116 g/l was obtained following the two-stage ED process. The
      total energy consumption for the D-glycerate concentration and its
      electroconversion to D-GA was approximately 0.92 kWh per 1 kg of D-GA.

PMID- 20674488
TI  - Effects of NREM sleep instability on cognitive processing.
AB  - OBJECTIVE: Cyclic alternating pattern (CAP) A1 subtypes, characterized by high
      voltage slow waves, are generated by the frontal cortex and are suspected to have
      a role in cognitive processing during NREM sleep. Conversely, CAP A2 and A3
      subtypes are characterized by variable amounts of rapid EEG potentials arising
      from the parietal-occipital areas and often coincide with arousals. We tested the
      hypothesis that CAP subtypes differentially correlate with cognitive functions.
      SUBJECTS AND METHODS: Eight healthy participants were recruited. Two nocturnal
      polysomnography studies and a series of neuropsychological tests were obtained in
      the subjects during the morning and afternoon of the first day and on the morning
      of the second day. RESULTS: In agreement with our original hypothesis, we found
      that CAP A1 subtypes were correlated with better neuropsychological functioning
      the day after, for verbal fluency, working memory, and both delayed recall and
      recognition of words. These same neuropsychological test results were found to be
      negatively correlated with CAP A2 subtypes. CAP A3 subtypes were negatively
      correlated with the Trial Making test Parts A and B. CONCLUSIONS: The results
      suggest that CAP A1 might be related to better cognitive functioning, whereas CAP
      A2 and A3 correlated with worse cognitive functioning. Further studies are needed
      to better understand how CAP influences cognitive performance, especially
      frontally-dependent functions and memory.

PMID- 20674489
TI  - Double-blind, randomized, placebo controlled trial on the effect of 10 days low
      frequency rTMS over the vertex on sleep in Parkinson's disease.
AB  - OBJECTIVE: A recent report indicates repetitive transcranial magnetic stimulation
      (rTMS) improves sleep in Parkinson's disease (PD). The aim of this work is to
      evaluate the effect of 10days rTMS on sleep parameters in PD patients. METHODS:
      Double-blind, placebo-controlled design. Eighteen idiopathic PD patients
      completed the study. Sleep parameters were evaluated through actigraphy and the
      Parkinson's Disease Sleep Scale (PDSS), along with depression (Hamilton
      Depression Rating Scale, HDS), and the Unified Parkinson's Disease Rating Scale
      (UPDRS). Evaluations were carried out before treatment with rTMS (pre-evaluation,
      PRE), after the rTMS treatment programme (post-evaluation, POST), and one week
      after POST (POST-2). Nine PD patients received real rTMS and the other 9 received
      sham rTMS daily for 10days, (100 pulses at 1Hz) applied with a large circular
      coil over the vertex. RESULTS: Stimulation had no effect over actigraphic
      variables. Conversely PDSS, HDS, and UPDRS were significantly improved by the
      stimulation. Notably, however, these changes were found equally in groups
      receiving real or sham stimulation. CONCLUSIONS: rTMS, using our protocol, has no
      therapeutic value on the sleep of PD patients, when compared to appropriate sham
      controls. Future works assessing the possible therapeutic role of rTMS on sleep
      in PD should control the effect of placebo.

PMID- 20674490
TI  - Prasinoderma singularis sp. nov. (Prasinophyceae, Chlorophyta), a solitary
      coccoid Prasinophyte from the South-East Pacific Ocean.
AB  - During the BIOSOPE cruise in the South-East Pacific Ocean in 2004, several
      unidentified strains of prasinophytes were isolated into culture. Of these, nine
      strains composed a group for which the partial 18S rRNA gene sequence was related
      to Prasinoderma coloniale. The ultrastructure, morphology, division process,
      pigment composition, genome size and molecular genetic phylogeny of these nine
      strains were investigated, using P. coloniale as a reference. The 18S rRNA gene
      sequence of P. singularis sp. nov. shares only 96.9% of identity with that of P.
      coloniale and contains a conserved insertion of 567bp length not recorded in P.
      coloniale. When compared to P. coloniale, P. singularis sp. nov. is
      morphologically characterized by the absence of colonies, smaller cells with a
      thinner cell wall, and a second cell type with a different cell covering.

PMID- 20674491
TI  - Dependence between volumes of protoplast and lorica in lugol-fixed tintinnid
      ciliates.
AB  - The relationship between the volume of tintinnid loricae and protoplasts was
      studied on the basis of bulk data derived from samples collected in a range of
      temperate environments: riverine, lacustrine, estuarine, and marine. All
      organisms were fixed with acid Lugol solution (0.5-1.0%). The dependence was
      described with the allometric equation: VL=2.74*VP(1.03), where VL and VP are
      volumes [MUm(3)] of loricae and protoplasts, respectively. The dependence was
      highly significant (p<0.001, n=417, R(2)=0.85). On average, protoplasts occupied
      31% of the lorica volume. One species, Helicostomella subulata,was omitted from
      the calculations and treated separately since this ciliate has a relatively large
      lorica. The relationship identified between lorica and protoplast volumes permits
      recalculating incomplete data if protoplasts are the only body part measured.

PMID- 20674492
TI  - Nosocomial infections and their control.

PMID- 20674493
TI  - Occupational exposure to motor exhaust in Stockholm, Sweden--different grouping
      strategies using variability in NO2 to create homogenous groups.
AB  - AIM: The aim of the present study was to investigate the personal variability in
      occupational exposure to NO(2), as a marker of exposure to diesel exhaust, and to
      compare a statistical method of grouping workers in homogenous groups with a
      grouping performed by a qualified occupational hygienist. METHODS: Forty-seven
      workers exposed to motor exhaust in their occupation were included. Personal
      measurements of NO(2) were performed with diffusive samplers over three full
      working shifts. The results from the measurements were analysed with a linear
      mixed effects model, taking both between and within-worker variability into
      consideration. The workers were divided into occupational groups in different
      ways in order to find a categorization, with maximal homogeneity in exposure in
      each group. We used (B)R(0.95) as an estimator of the between-worker variability.
      To study the effect of the divisions on the fit of the statistical model, we used
      the Akaike Information Criterion. RESULTS: The geometric mean for NO(2) for all
      47 workers was 69 MUg/m(3) and the between-worker variability (B)R(0.95) was
      23.8. In six successive steps, the 47 workers were divided into up to eight
      groups, based on observed job characteristics. In the final grouping, seven
      groups were included with geometric means ranging from 32 MUg/m(3) for outdoor
      workers, to 316 MUg/m(3) for the most exposed group (tunnel construction
      workers). The (B)R(0.95) varied between 2.4 and 6.3. The within-worker
      variability (W)R(0.95) for the last division differed in the groups from 2.0 to
      7.9. The Akaike Information Criterion decreased from 246, if all persons were
      included in one group, to 174 for the final grouping. CONCLUSIONS: The average
      level of NO(2) varied about 10 times between the different occupational groups,
      with the highest level for tunnel construction workers (316 MUg/m(3)) and lowest
      for outdoor workers (32 MUg/m(3)). For four of the seven groups the between
      worker variability was higher than the within-worker variability.

PMID- 20674494
TI  - What's popular in sports medicine and sports science research?

PMID- 20674495
TI  - Heart fatty acid binding protein (H-FABP) as a diagnostic biomarker in patients
      with acute coronary syndrome.
AB  - AIMS AND OBJECTIVES: Diagnosis of myocardial ischaemia at an early stage in the
      emergency department is often difficult. A recently proposed biomarker, heart
      fatty acid binding protein (H-FABP) has been found to appear in the circulation
      superior to that of cardiac troponins in the early hours of acute coronary
      syndrome. We proposed to evaluate the levels of H-FABP and ascertain its utility
      as an early biomarker for acute coronary syndrome (ACS). METHODS AND RESULTS: The
      present study was carried out in 485 subjects, of whom 297 were diagnosed as
      patients with ACS, 89 were diagnosed as non-cardiac chest pain (NCCP) and 99
      people served as healthy controls. H-FABP levels were measured in comparison with
      standard markers such as troponin I and CK-MB in all subjects enrolled in the
      study. The levels of H-FABP were significantly raised in patients when compared
      to controls and NCCP (P<0.001). Receiver Operator Characteristic Curve (ROC)
      analysis showed H-FABP to be a good discriminator between patients with ischaemic
      heart disease and patients without ischaemic heart disease. The area under the
      curve was found to be 0.965 with 95% CI (0.945-0.979). The cut-off value above
      which H-FABP can be considered positive was found to be 17.7ng/ml. CONCLUSION: H
      FABP is a promising biomarker for the early detection of patients with acute
      coronary syndrome.

PMID- 20674496
TI  - Recent advances in critical care medicine relevant to cardiac surgery.
AB  - Many advances have taken place in intensive care, which are based on large
      multicentre randomised controlled trials or large observational studies which
      control for multiple variables. Of particular importance to cardiac surgery
      patients have been the NICE study of glycaemic control in ICU and the SAFE study
      of fluid resuscitation in ICU. These studies have established the standard of
      care for the control of glycaemia in ICU patients and the conditions which
      require albumin fluid resuscitation as opposed to crystalloid resuscitation in
      ICU and vice versa. A large study of resuscitation with starch is currently under
      way. There is also remaining concern about the effect of blood on outcome in
      cardiac surgery patients. Observational studies have established an independent
      association between the transfusion of older red cells and increased risk of
      death in ICU patients. Such findings suggest caution with excessive transfusion
      after cardiac surgery and the need for a large randomised controlled trial.

PMID- 20674497
TI  - Perioperative metabolic therapy improves redox status and outcomes in cardiac
      surgery patients: a randomised trial.
AB  - OBJECTIVE: Perioperative therapy with antioxidants and metabolic substrates has
      the potential to reduce oxidative stress and improve recovery from cardiac
      surgery, particularly in elderly and high risk cases. The aim of this study was
      to assess the effect of perioperative metabolic therapy at a biochemical,
      clinical and economic level in cardiac surgical patients. METHODS: Patients
      (n=117, mean age 65 +/- 1.0 years, 74% male) undergoing elective coronary artery
      bypass graft (CABG) and/or valve surgery in 2004-2006 were randomised to receive
      in double blinded fashion, while on the waiting list for surgery (approximately
      two months) and one month after surgery, either metabolic therapy (coenzyme
      Q(10), magnesium orotate, lipoic acid, omega-3 fatty acids and selenium) or
      placebo. Biochemical and clinical outcomes were assessed. RESULTS: Cardiac
      surgery increased oxidative stress and decreased plasma levels of key
      antioxidants. Metabolic therapy for a mean of 76 +/- 7.5 days increased
      antioxidant levels preoperatively so that the adverse effect of surgery on redox
      status was attenuated. Metabolic therapy reduced plasma troponin I, 24 hours
      postoperatively from 1.5 (1.2-1.8) (geometric mean 95% CI) MUg/L, to 2.1 (1.8
      2.6) MUg/L (P=0.003) and shortened the mean length of postoperative hospital stay
      by 1.2 days from 8.1 (7.5-8.7) to 6.9 (6.4-7.4) days (P=0.004) and reduced
      hospital costs. Metabolic therapy was inexpensive and had no clinically
      significant side effects. CONCLUSIONS: Perioperative metabolic therapy for
      cardiac surgery is safe and inexpensive and is associated with improved redox
      status, reduced myocardial damage, and shortened length of postoperative hospital
      stay.

PMID- 20674498
TI  - Feedback of trial results to participants: a survey of clinicians' and patients'
      attitudes and experiences.
AB  - PURPOSE: There is growing interest in the provision of trial results to trial
      participants. However, there are a number of gaps in the research base relating
      to the closure of clinical trials and feedback of results to participants.
      METHODS: The aim of this research was to explore the practice of feeding back
      trial results to trial participants and to identify best practice in this area.
      Postal questionnaires were sent to members of the UK National Cancer Research
      Institute Clinical Studies Groups (NCRI CSG) and to patients over the age of 18
      years who completed trial treatment (located in one Cancer Network) during a 16
      month period (April 07-July 08). RESULTS: 145 NCRI CSG member surveys and 81
      patient questionnaires were returned. The vast majority of all respondents
      supported the idea of offering results to trial participants. However, NCRI
      members and trial participants differed in their opinions about the timing and
      method for the provision of results. CONCLUSION: The results provide an insight
      into the views of these groups in relation to desire for results and practical
      aspects of results feedback which should inform further investigations into trial
      management and the practice of feedback of trial results.

PMID- 20674500
TI  - Communication skills training in end of life care--short of the mark?

PMID- 20674499
TI  - Short-term and long-term elderly cancer survivors: a population-based comparative
      and controlled study of morbidity, psychosocial situation, and lifestyle.
AB  - PURPOSE: The aim of this study was to compare how short-term (1-5 years) and long
      term (>=5 years) elderly cancer survivors and matched cancer-free controls report
      their morbidity, psychosocial situation, lifestyle and rurality. METHODS: Among
      11,899 persons aged >=70 years who participated in the second Health Survey of
      North-Trondelag County (1995-1997), 479 had been diagnosed with invasive primary
      cancer 1-10 years before the survey according to Cancer Registry of Norway and
      self-report. Each patient was randomly age- and gender-matched with three
      controls without cancer (N=1437). Descriptive statistics was performed. RESULTS:
      The cancer sample consisted of 265 (55%) short-term and 214 (45%) long-term
      survivors, where 223 (47%) lived in rural and 256 (53%) lived in urban areas. No
      significant differences were found when comparing short and long-term survivors.
      When all cancer survivors were compared with controls, the survivors reported
      significantly poorer 'self-rated health', and more 'visits to a medical doctor'.
      Stepwise logistic regression analysis explained 3.3% variance in being cancer
      survivors, with 'visits to a medical doctor' and 'personal activity of daily
      living problems' as variables contributing to the model. Rural versus urban areas
      of living explained 6.3% variance in being a rural inhabitant, with 'self
      reported health' as the variable showing significant contribution to the model.
      CONCLUSION: Short and long-term older cancer survivors showed similar
      psychosocial situation, morbidity, and lifestyle. Compared to cancer-free
      controls, survivors reported poorer health, more activity of daily living
      problems, and more frequently medical consultations. Elderly cancer survivors
      living in rural areas reported poorer health than those living in urban areas.

PMID- 20674501
TI  - Single layer centrifugation of stallion spermatozoa improves sperm quality
      compared with sperm washing.
AB  - This study compared the effect on semen quality of different handling methods
      used in the preparation of stallion semen doses for artificial insemination. The
      three methods were (i) extending the ejaculate to 30-50 x 10(6)/ml, (ii) single
      layer centrifugation (SLC) and (iii) sperm washing (centrifugation without a
      colloid). An additional treatment was to add seminal plasma (SP) in various
      proportions to some SLC preparations. The resulting samples were evaluated for
      sperm motility by computer assisted sperm analysis, membrane integrity using the
      Nucleocounter SP-100 and chromatin integrity by the sperm chromatin structure
      assay. SLC samples consistently had better sperm quality than the extended
      samples. Sperm washing did not confer any beneficial effect compared with the
      extended samples and these samples had significantly worse sperm quality than the
      SLC samples (motility, P<0.01; viability, P<0.001). There was no evidence to
      suggest that adding SP to the SLC samples could enhance sperm motility for more
      than a few hours. Longer term cold storage of spermatozoa in the presence of
      small concentrations of SP resulted in a reduction in total motility and
      progressive motility compared with SLC alone. High concentrations of SP were
      detrimental to sperm survival.

PMID- 20674502
TI  - Bar code-based pre-transfusion check in pre-operative autologous blood donation.
AB  - BACKGROUND: The objective of this study was to demonstrate the feasibility of a
      bar code-based identification system for the pre-transfusion check at the bedside
      in the setting of pre-operative autologous blood donation (PABD). MATERIALS AND
      METHODS: Between July 2003 and December 2008 we determined the compliance rate
      and causes of failure of electronic bedside checking for PABD transfusion.
      RESULTS: A total of 5627 (9% of all transfusions) PABD units were administered
      without a single mistransfusion. The overall rate of compliance with electronic
      checking was 99%. CONCLUSIONS: The bar code-based identification system was
      applicable to the pre-transfusion check for PABD transfusion.

PMID- 20674503
TI  - The effect of self-efficacy on cardiovascular lifestyle.
AB  - BACKGROUND: It is important that patients with vascular diseases adopt a healthy
      lifestyle so as to reduce vascular risk. Since self-efficacy is an important
      precondition for health behavior change in patients with chronic disease, we
      investigated whether self-efficacy was associated with cardiovascular lifestyle
      in patients with clinical manifestations of vascular diseases. METHODS AND
      DESIGN: In this observational cohort study, 125 patients who had recently been
      referred for cerebrovascular disease, coronary heart disease, or peripheral
      arterial disease participated in a 1-year self-management intervention. They
      completed a self-efficacy questionnaire and questions about their cardiovascular
      lifestyle at baseline and after 1 year. Logistic regression analyses were
      performed to quantify the impact of change in self-efficacy on physical activity,
      smoking behavior, alcohol consumption, and food choices. RESULTS: Improved self
      efficacy was associated with improved adherence to guidelines for physical
      activity (OR 3.5, 95%CI 1.0-11.0) and food choices (B 0.15, 95%CI 0.00-0.31). No
      such improvement was seen regarding adherence to guidelines for smoking or
      alcohol intake. CONCLUSION: In patients with vascular diseases, improvements in
      self-efficacy are associated with an improvement in cardiovascular lifestyle,
      namely, more exercise and better food choices.

PMID- 20674504
TI  - Management of recurrent epididymitis in children: application of neurovascular
      sparing vas clipping in refractory cases.
AB  - PURPOSE: To investigate the efficacy of therapeutic methods for recurrent
      epididymitis and neurovascular sparing vas clipping in refractory cases.
      MATERIALS AND METHODS: Fifteen boys with recurrent epididymitis were enrolled:
      the first group (9) with primary structural anomalies and the second group (6)
      with voiding dysfunction without structural anomalies. Median age was 4 (29
      months to 7 years) and 4.5 (6 months to 11 years) years, respectively. Mean
      follow up was 7.5 (2-11) and 5.2 (3.5-8) years, respectively. RESULTS:
      Urethrovasal reflux was detected in all patients of the first group except one.
      Endoscopic injection of bulking agent was successfully applied in three patients
      with no recurrent epididymitis. No further episodes of epididymitis were reported
      after valve ablation or clean intermittent catheterization. In four non
      responders, vas clipping was successfully undertaken. Voiding dysfunction was the
      possible etiology of epididymitis but with no obvious urethrovasal reflux in the
      second group. No further episodes of epididymitis occurred using bladder
      retraining and medications for detrusor and sphincter relaxation. CONCLUSIONS:
      The results suggest that neurovascular sparing vas clipping can be used
      effectively in children with structural anomalies and urethrovasal reflux who
      have developed intractable epididymitis.

PMID- 20674505
TI  - CD45RA expression on HCMV-specific effector memory CD8+ T cells is associated
      with the duration and intensity of HCMV replication after transplantation.
AB  - In this cross-sectional study on 42 solid organ transplant recipients, the
      association of kinetics of human cytomegalovirus (HCMV) replication and EMRA HCMV
      specific CD8+ T cells was investigated. Correlation was observed between the
      duration of HCMV replication after transplantation and CD45RA+CD27- (r=0.609;
      p=0.004), CD45RA+CD28- (r=0.579; p=0.008) or CD45RA+CCR7- (r=0.488; p=0.029) HCMV
      specific CD8+ T cells percentages. In the multivariate regression analyses,
      CD45RA+CD27-, CD45RA+CD28- or CD45RA+CCR7- HCMV-specific CD8+ T cells percentages
      increased 5.58% (p=0.001), 5.35% (p=0.001) or 4.49% (p=0.012), respectively, with
      every 10-day increase in the duration of HCMV replication. Moreover, CD45RA+CD27-
      or CD45RA+CD28- frequencies increased 4.16% (p=0.024) or 3.58% (p=0.049),
      respectively, with every unity increase in log(10) genomes/mL. These observations
      support the major association between the frequency of EMRA HCMV-specific CD8+ T
      cells and the duration of post-transplant HCMV replication episodes in solid
      organ transplantation recipients.

PMID- 20674506
TI  - Alternatively activated alveolar macrophages in pulmonary fibrosis-mediator
      production and intracellular signal transduction.
AB  - Activated macrophages have been characterized as M1 and M2 according to their
      inflammatory response pattern. Here we analyzed the M2 marker expression and
      intracellular signal transduction in the course of cytokine-driven
      differentiation. We found elevated spontaneous production of the chemokines
      CCL17, CCL18 and CCL22 and increased expression of CD206 by alveolar macrophages
      from patients with lung fibrosis. Stimulation of normal human AM with Th2
      cytokines IL-4 and/or IL-10 in vitro revealed IL-4 as the most powerful inducer
      of M2-phenotype in AM and monocytes. Importantly, IL-10 enhanced IL-4-induced
      expression of CCL18 and IL-1RA in a synergistic fashion. IL-4/IL-10 stimulation
      induces a strong activation of STAT3 in AM from fibrosis patients. These results
      suggest an important role for M2 polarized AM in the pathogenesis of pulmonary
      fibrosis and indicate that both IL-4 and IL-10 account for human AM phenotype
      shift to M2, as seen in patients with fibrotic interstitial lung diseases.

PMID- 20674508
TI  - Seizure prediction: the Fourth International Workshop.
AB  - The recently convened Fourth International Workshop on Seizure Prediction (IWSP4)
      brought together a diverse international group of investigators, from academia
      and industry, including epileptologists, neurosurgeons, neuroscientists, computer
      scientists, engineers, physicists, and mathematicians who are conducting
      interdisciplinary research on the prediction and control of seizures. IWSP4
      allowed the presentation and discussion of results, an exchange of ideas, an
      assessment of the status of seizure prediction, control, and related fields, and
      the fostering of collaborative projects.

PMID- 20674507
TI  - Differentiation of attention-related problems in childhood absence epilepsy.
AB  - The current study examined the specific types of attention-related problems
      children with childhood absence epilepsy (CAE) experience and the role of disease
      factors in the development of attention-related problems. Thirty-eight subjects
      with CAE and 46 healthy controls, aged 6 to 16, participated in the study. The
      Behavior Assessment System for Children (BASC) was completed by parents, and the
      Attention Problems and Hyperactivity subscales were used to characterize the
      problems of children with CAE. Item analysis within the subscales revealed that
      children with CAE demonstrate higher rates of hyperactive (overactivity and
      fidgetiness) and inattentive (forgetfulness and distractibility) problems, and
      require more supervision. Within-CAE-group analyses revealed that those who were
      actively having seizures were more impatient and those with a longer duration of
      illness were less proficient in completing homework. Children with CAE are at
      risk for certain inattentive and hyperactive problems, which can differ depending
      on duration of illness and active seizure status.

PMID- 20674509
TI  - Abdominal pain 1 month after adjustable gastric banding: an unusual complication
      caused by connecting tubing.

PMID- 20674510
TI  - Unidirectional barbed suture versus continuous suture with intracorporeal knots
      in laparoscopic myomectomy: a randomized study.
AB  - STUDY OBJECTIVE: To estimate the effectiveness of unidirectional knotless barbed
      suture and continuous suture with intracorporeal knots in the repair of uterine
      wall defects during laparoscopic myomectomy. DESIGN: Randomized clinical study
      (Canadian Task Force Classification I). SETTING: Single-center study in a
      university hospital. PATIENTS: This study enrolled 44 women who underwent
      laparoscopic myomectomy. INTERVENTIONS: In accord with to the randomization, the
      uterine wall defects were closed either with a continuous suture with
      intracorporeal knots (group V) or a unidirectional knotless barbed suture (group
      L). MEASUREMENTS AND MAIN RESULTS: The time required to suture the uterine wall
      defect was significantly lower in group L (11.5 +/- 4.1 minutes) than in group V
      (17.4 +/- 3.8 minutes; p <.001). However, no significant difference was observed
      in the operative time between the 2 study groups. The intraoperative blood loss
      was significantly lower in group L than in group V (p =.004). The degree of
      surgical difficulty was significantly lower in group L (3.7 +/- 1.1) than in
      group V (6.1 +/- 2.1; p <.001). CONCLUSION: The unidirectional knotless barbed
      suture may facilitate the suture of uterine wall defects during laparoscopic
      myomectomy. When compared with continuous suture and intracorporeal knots, the
      barbed suture reduces the time required to suture the uterine wall defect and the
      intraoperative blood loss.

PMID- 20674511
TI  - Calbindin-immunoreactive cells in the fish enteric nervous system.
AB  - Calbindin is present in a large proportion of the intrinsic primary afferent
      neurons (IPANs) in the mammalian gut. Little is known about either calbindin or
      IPANs in fish. In the present study, calbindin immunoreactivity was investigated
      in the enteric nervous system of the teleost shorthorn sculpin (Myoxocephalus
      scorpius). Calbindin-immunoreactive nerve cell bodies and nerve fibres were
      present in all the gut regions except the cardiac stomach. The highest proportion
      was found in the proximal intestine where calbindin-immunoreactive cells
      constituted 59+/-6% (N=3) of the total Hu C/D-immunoreactive myenteric nerve cell
      population. In other regions, calbindin-immunoreactive cells constituted around
      30% of the total population. The cells were generally multipolar with one long
      axon. The size distribution differed significantly between calbindin-positive and
      calbindin-negative cells in each of the three animals examined. Calbindin
      positive neurons in the proximal intestine had a mean cross-sectional soma area
      of 163+/-73MUm(2) (n=183 cells) while calbindin-negative cells were 348+/
      221MUm(2) (n=127 cells). Calbindin immunoreactivity colocalised to a large extent
      with serotonin immunoreactivity, but not with choline acetyltransferase (ChAT)
      immunoreactivity. Thus, the calbindin-immunoreactive nerve cell population in the
      shorthorn sculpin gut seems to constitute a homogenous subpopulation of the
      enteric neurons, at least when considering the size and content of some
      transmitters. Whether markers other than serotonin and ChAT would differentiate
      the population remains to be tested. In conclusion, the calbindin-immunoreactive
      cells in the sculpin differ from mammalian IPANs with regard to several
      parameters and future functional studies could hopefully add information about
      the role of this large group of cells in the fish enteric nervous system.

PMID- 20674512
TI  - Circadian changes in autonomic function in conscious rats with heart failure:
      effects of amiodarone on sympathetic surge.
AB  - Cardiovascular events are characterized by circadian periodicity with a peak
      prevalence during the awakening period, which suggests a morning surge in
      sympathetic activity. We developed an experimental system to determine circadian
      changes in heart rate (HR), blood pressure (BP), locomotor activity (Loc),
      respiratory rate and autonomic function in conscious, unrestrained rats. The
      effects of amiodarone on circadian variation of these variables were determined
      in rats with myocardial infarction and subsequent congestive heart failure (CHF).
      We continuously recorded BP, HR and Loc for 24h in rats with CHF (n=16) or after
      a sham operation (Sham; n=7). To determine circadian changes in sympathovagal
      balance, digitized BP and HR data throughout 24h were analyzed based on maximum
      entropy. The study was repeated after 3 weeks of oral amiodarone (50mg/kg/day) or
      saline administration. Baseline HR, mean BP, and Loc were higher in the dark
      period than in the light period (all p<0.05) in both CHF and Sham rats, which is
      consistent with the circadian periodicity of nocturnal animals. Low-frequency
      components of diastolic BP variability (LFdp), an index of sympathetic tone, were
      significantly higher during the awakening period (16:00-20:00) than during the
      sleeping period (08:00-14:00), a finding analogous to the sympathetic morning
      surge in men. Amiodarone suppressed this transient increase in LFdp power during
      the awakening period. Our experimental system could detect sympathetic surge in
      conscious rats. Amiodarone suppressed the sympathetic surge, which could explain,
      at least in part, beneficial effects of amiodarone in patients with CHF.

PMID- 20674513
TI  - Mouse CSB protein is important for gene expression in the presence of a single
      strand break in the non-transcribed DNA strand.
AB  - CSB protein is required for strand-specific repair of bulky DNA lesions in
      transcribed genes and mediates transcription recovery after exposure to DNA
      damaging agents. We enzymatically generated DNA single-strand breaks (SSBs) with
      3'-OH and 5'-phosphate termini in defined positions of a plasmid-borne gene and
      measured their effect on transcription in cell lines with different statuses of
      the Csb gene. A single SSB in the transcribed region of the gene caused
      significant decrease of gene expression. In all tested cell lines of mouse and
      human origin, a SSB in the transcribed DNA strand was less harmful for gene
      expression than a SSB situated in the opposing DNA strand. CSB deficiency
      exhibited no effect on the expression of the nicked DNA in human fibroblasts
      immortalised by SV40 large T-antigen but caused a very strong decrease of gene
      expression in spontaneously transformed mouse embryonic fibroblasts (MEFs).
      Compared to the corresponding CSB-proficient MEFs, the effect was on average 6.7
      fold stronger for a defined SSB located in the non-transcribed DNA strand, but
      only 2.4-fold for a SSB in the transcribed strand and 1.7-fold for a SSB located
      in the non-genic region. At the same time, CSB deficiency did not compromise the
      overall efficiency of repair of SSBs generated by treatment of the cells with
      hydrogen peroxide. The gene expression data thus indicate that CSB prevents
      irreversible transcription failures at the sites of DNA damage, acting
      preferentially at SSBs located in the non-transcribed DNA strand of the
      transcribed genes. We further conclude that SSBs in the non-transcribed DNA
      strand are commonly more harmful for transcription than those situated in the
      transcribed strand.

PMID- 20674514
TI  - Determination of hypersensitivity to genotoxic agents among Escherichia coli
      single gene knockout mutants.
AB  - We have tested the KEIO collection of 3985 different viable single gene knockouts
      in Escherichia coli to identify genes whose loss increases sensitivity to one or
      more of six different chemotherapeutic agents and mutagens: Bleomycin (BLM),
      Cisplatin (CPT), ICR-191 (ICR), 5-azacytidine (5AZ), Zebularine (ZEB), and 5
      bromo-2'-deoxyuridine (5BdU). We discovered a set of 156 strains that display a
      significant increase in sensitivity to at least one of the agents tested. Each
      genotoxic agent generates a distinct "sensitivity profile" that is characteristic
      of the agent. Comparison with an independent study of sensitivity profiles for an
      extensive set of antibiotics pinpoints those effects that are relatively specific
      for each agent. In some cases engineered double mutants have greatly increased
      effects. These results provide insight into the mechanism of action of each
      agent, and define targets for the design of co-drugs that can potentiate these
      agents. An example is the finding that mutants lacking one of several genes in
      the folate biosynthetic pathway are hypersensitive to ZEB, leading to a
      demonstration of synergy between trimethoprim and ZEB.

PMID- 20674515
TI  - Regulation of tolerance to DNA alkylating damage by Dot1 and Rad53 in
      Saccharomyces cerevisiae.
AB  - To maintain genomic integrity cells have to respond properly to a variety of
      exogenous and endogenous factors that produce genome injuries and interfere with
      DNA replication. DNA integrity checkpoints coordinate this response by slowing
      cell cycle progression to provide time for the cell to repair the damage,
      stabilizing replication forks and stimulating DNA repair to restore the original
      DNA sequence and structure. In addition, there are also mechanisms of damage
      tolerance, such as translesion synthesis (TLS), which are important for survival
      after DNA damage. TLS allows replication to continue without removing the damage,
      but results in a higher frequency of mutagenesis. Here, we investigate the
      functional contribution of the Dot1 histone methyltransferase and the Rad53
      checkpoint kinase to TLS regulation in Saccharomyces cerevisiae. We demonstrate
      that the Dot1-dependent status of H3K79 methylation modulates the resistance to
      the alkylating agent MMS, which depends on PCNA ubiquitylation at lysine 164.
      Strikingkly, either the absence of DOT1, which prevents full activation of Rad53,
      or the expression of an HA-tagged version of RAD53, which produces low amounts of
      the kinase, confer increased MMS resistance. However, the dot1Delta rad53-HA
      double mutant is hypersensitive to MMS and shows barely detectable amounts of
      activated kinase. Furthermore, moderate overexpression of RAD53 partially
      suppresses the MMS resistance of dot1Delta. In addition, we show that MMS-treated
      dot1Delta and rad53-HA cells display increased number of chromosome-associated
      Rev1 foci. We propose that threshold levels of Rad53 activity exquisitely
      modulate the tolerance to alkylating damage at least by controlling the abundance
      of the key TLS factor Rev1 bound to chromatin.

PMID- 20674516
TI  - Proficient repair in chromatin remodeling defective ino80 mutants of
      Saccharomyces cerevisiae highlights replication defects as the main contributor
      to DNA damage sensitivity.
AB  - Ino80 is an evolutionarily conserved member of the SWI2/SNF2-family of ATPases in
      Saccharomyces cerevisiae. It resides in a multiprotein helicase/chromatin
      remodeling complex, and has been shown to play a key role in the stability of
      replication forks during replication stress. Though yeast with defects in ino80
      show sensitivity to killing by a variety of DNA-damaging agents, a role for the
      INO80 protein complex in the repair of DNA has only been assessed for double
      strand breaks, and the results are contradictory and inconclusive. We report that
      ino80Delta cells are hypersensitive to DNA base lesions induced by ultraviolet
      (UV) radiation and methyl methanesulfonate (MMS), but show little (or no)
      increased sensitivity to the DNA double-strand break (DSB)-inducing agents
      ionizing radiation and camptothecin. Importantly, ino80Delta cells display
      efficient removal of UV-induced cyclobutane pyrimidine dimers, and show a normal
      rate of removal of DNA methylation damage after MMS exposure. In addition,
      ino80Delta cells have an overall normal rate of repair of DSBs induced by
      ionizing radiation. Altogether, our data support a model of INO80 as an important
      suppressor of genome instability in yeast involved in DNA damage tolerance
      through a role in stability and recovery of broken replication forks, but not in
      the repair of lesions leading to such events. This conclusion is in contrast to
      strong evidence for the DNA repair-promoting role of the corresponding INO80
      complexes in higher eukaryotes. Thus, our results provide insight into the
      specialized roles of the INO80 subunits and the differential needs of different
      species for chromatin remodeling complexes in genome maintenance.

PMID- 20674517
TI  - An Artemis polymorphic variant reduces Artemis activity and confers cellular
      radiosensitivity.
AB  - Artemis is required for V(D)J recombination and the repair of a subset of
      radiation-induced DNA double strand breaks (DSBs). Artemis-null patients display
      radiosensitivity (RS) and severe combined immunodeficiency (SCID), classified as
      RS-SCID. Strongly impacting hypomorphic Artemis mutations confer marked infant
      immunodeficiency and a predisposition for EBV-associated lymphomas. Here, we
      provide evidence that a polymorphic Artemis variant (c.512C > G: p.171P > R),
      which has a world-wide prevalence of 15%, is functionally impacting. The c.512C >
      G mutation causes an approximately 3-fold decrease in Artemis endonuclease
      activity in vitro. Cells derived from a patient who expressed a single Artemis
      allele with the polymorphic mutational change, showed radiosensitivity and a DSB
      repair defect in G2 phase, with Artemis cDNA expression rescuing both phenotypes.
      The c.512C > G change has an additive impact on Artemis function when combined
      with a novel C-terminal truncating mutation (p.436C > X), which also partially
      inactivates Artemis activity. Collectively, our findings provide strong evidence
      that monoallelic expression of the c.512C > G variant impairs Artemis function
      causing significant radiosensitivity and a G2 phase DSB repair defect. The
      patient exhibiting monoallelic c.512C > G-Artemis expression showed
      immunodeficiency only in adulthood, developed bilateral carcinoma of the nipple
      and myelodysplasia raising the possibility that modestly decreased Artemis
      function can impact clinically.

PMID- 20674518
TI  - Characteristics of gastroesophageal reflux in adults with cystic fibrosis.
AB  - BACKGROUND: Gastroesophageal reflux (GER) in adults with cystic fibrosis (CF) is
      poorly characterized. This study examines the frequency and predictors of GER
      symptoms and their relationship to lung function in adults with CF. METHODS:
      Cross-sectional study of adults at the University of Minnesota CF Clinic using
      two validated self report surveys: The Mayo GER questionnaire and the GERD
      Symptom Assessment Scale (GSAS). RESULTS: Of 274 invited patients, 201 (73%)
      completed the surveys and 173 performed spirometry at the same visit. Frequent
      symptoms (at least weekly) were reported by 24% of the patients and an additional
      39% experienced occasional symptoms. Heartburn, acid regurgitation and dysphagia
      were the most common symptoms and 18% reported that GER symptoms worsened their
      respiratory condition. Females and patients reporting weight loss had more
      symptoms (mean GSAS symptom score 4.9 vs. 4.0, p=0.025 and 5.3 vs. 4.2, p=0.04)
      and more severe symptoms (mean GSAS distress score 5.6 vs. 3.8, p=0.005 and 6.8
      vs. 4.0, p=0.01) compared to males and those who did not report weight loss.
      Patients on acid suppression (n=122, 61%) continued to report heartburn (n=80,
      66%) and acid regurgitation (n=47, 23%). GER symptoms and severity of symptoms
      were not predictive of FEV(1) or FVC. CONCLUSIONS: GER symptoms were present in a
      majority of patients. Females and patients with weight loss require special
      attention to their GER symptoms. Many patients on acid suppression continued to
      be report symptoms.

PMID- 20674519
TI  - Accelerating high quality bioanalytical LC/MS/MS assays using fused-core columns.
AB  - High quality, ultra-fast bioanalytical LC/MS/MS methods were developed using
      short columns packed with fused-core particles and high (1.0-3.0 mL/min) flow
      rates. For more than two years, at flow rates up to 3.0 mL/min, using 0.33 min
      non-ballistic gradients, these methods were shown to provide comparable or better
      performance than slower assays for accuracy, precision, sensitivity, specificity,
      and ruggedness, and met all criteria required by the bioanalytical regulatory
      guidance.

PMID- 20674520
TI  - Molecularly-imprinted microspheres for selective extraction and determination of
      melamine in milk and feed using gas chromatography-mass spectrometry.
AB  - Molecularly-imprinted polymers in the form of microspheres were synthesized using
      the dispersion polymerization protocol; cyromazine was used as dummy template,
      while methacrylic acid, ethylene glycol dimethacrylate and acetonitrile (MeCN)
      were used as functional monomer, cross-linker, and porogen, respectively. When
      compared with the non-imprinted polymer, the molecularly-imprinted polymers
      (MIPs) showed outstanding affinity toward melamine in MeCN with a maximum binding
      concentration (B(max)) of 53.20 nmol mg(-1) MIPs, imprinting effect of 4.6, and a
      dissociation constant (K(d)) of 90.45 microM. After optimization of the
      molecularly-imprinted solid-phase extraction conditions, a new method was
      developed to determine the melamine in milk and feed with gas chromatography-mass
      spectrometry. The performance of this method has been evaluated in the tainted
      milk and feed in terms of recovery, precision, linearity, the limit of detection
      (LOD) and limit of quantitation (LOQ). Recovery ranged in samples from 93.1 to
      101.3% with intra-day and inter-day relative standard deviation values below
      5.34%. The LOD and LOQ of melamine in milk and feed were 0.01 microg mL(-1)
      (microg g(-1)) and 0.05 microg mL(-1) (microg g(-1)), respectively.

PMID- 20674521
TI  - Validated GC/MS method for the simultaneous determination of clozapine and
      norclozapine in human plasma. Application in psychiatric patients under clozapine
      treatment.
AB  - A sensitive and specific GC/MS method for the determination of clozapine (CLZ)
      and its major metabolite norclozapine (NCLZ), in plasma has been developed,
      optimized and validated. Specimen preparation includes solid-phase extraction of
      both analytes using Bond-Elut Certify cartridge and further derivatization with
      TFAA. Clozapine-d8 was used as internal standard for the determination of CLZ and
      NCLZ. Limits of detection were 0.45 ng/mL for CLZ and 1.59 ng/mL for NCLZ, while
      limits of quantification were 1.37 ng/mL for CLZ and 4.8 ng/mL for NCLZ, as
      calculated by the calibration curves. The calibration curves were linear up to
      600 ng/mL for CLZ and NCLZ. Absolute recovery ranged from 82.22% to 95.35% for
      both analytes. Intra- and interday accuracy was less than 7.13% and --12.52%,
      respectively, while intra- and interday precision was between 9.47% and 12.07%,
      respectively, for CLZ and NCLZ. The method covers all therapeutic range and
      proved suitable for the determination of CLZ and NCLZ not only in psychiatric
      patients but also in forensic cases with clozapine implication.

PMID- 20674522
TI  - Development and validation of sensitive and selective LC-MS/MS methods for the
      determination of BMS-708163, a gamma-secretase inhibitor, in plasma and
      cerebrospinal fluid using deprotonated or formate adduct ions as precursor ions.
AB  - BMS-708163 is a gamma-secretase inhibitor that is being developed for the
      treatment of Alzheimer's disease. Several LC-MS/MS methods have been developed
      for the determination of BMS-708163 in both plasma and cerebrospinal fluid in
      support of dog, rat, mouse and human studies. To support non-clinical studies, an
      LC-MS/MS method with a lower limit of quantitation (LLOQ) of 5 ng/mL, was
      developed and validated in dog, rat, and mouse plasma by using the deprotonated
      ion as the precursor ion. To support clinical studies, an LC-MS/MS method with
      LLOQ of 0.1 ng/mL, was developed and validated in human plasma by using the
      formate adduct as the precursor ion. Formic acid (0.01%) in water and
      acetonitrile was found to be the most favorable mobile phases for both
      deprotonated and formate adduct ions in negative electrospray ionization mode. A
      combination of a 3M Empore C18 plate for SPE and a Waters Atlantis dC18
      analytical column for separation was used to achieve a highly selective solid
      phase extraction and chromatographic procedure from plasma without dry down and
      reconstitution steps. In the development of an assay for BMS-708163 in cerebral
      spinal fluid (CSF), significant non-specific binding of BMS-708163 was observed
      and resolved with pre- or post-spike of 0.2% Tween 20 into CSF samples. A dilute
      and-shoot LC-MS/MS method with LLOQ of 0.1 ng/mL was developed and validated to
      assess BMS-708163 exposure in human CSF.

PMID- 20674523
TI  - Any use in proteomics for low-tech approaches? Detecting fibrinogen chains of
      different animal species in two-dimensional electrophoresis patterns.
AB  - We characterized the two-dimensional electrophoretic patterns of fibrinogen
      chains alpha, beta, and gamma from the plasma of six animal species -Bos taurus,
      Canis familiaris, Equus caballus, Felis catus, Gallus domesticus and Sus scrofa.
      Comparing the spots resolved from serum and plasma samples, or exploiting the
      cross-reactivity of animal fibrinogen with an antiserum raised against the human
      protein could detect only some of the fibrinogen chains. Conversely, the analysis
      of the precipitate obtained by heating plasma for some minutes at 56 degrees C
      was adequate for the recognition of all fibrinogen chains in all samples.
      Physicochemical properties of the homologous proteins were found to extensively
      vary across species, with complete separation among the mapping areas for alpha,
      beta and gamma chains and maximal heterogeneity among beta chains.

PMID- 20674524
TI  - Multiples clinic: a model for antenatal care.
AB  - Antenatal care has become more focused in recent years with an increase in the
      number of specialist clinics providing care in a multidisciplinary manner.
      Multiple pregnancies are complex with complications for the mother and babies
      arising frequently. As a group they lend themselves well to a specialist clinic
      model where interested doctors and midwives can provide care tailored to the
      individual. This makes it less likely that complications will be missed and
      provides a consistent approach to care that patients desire. This article aims to
      describe models of care that can be given in such a clinic, acknowledging that
      one model will not fit all. The scant evidence that exists is presented along
      with selected examples of individual complications.

PMID- 20674525
TI  - Funding criteria for common procedures: a postcode lottery in NHS plastic
      surgery.

PMID- 20674526
TI  - An overview of methods for vascular mapping in the planning of free flaps.
AB  - INTRODUCTION: The aim of this overview is to describe the various methods for
      vascular mapping of flaps together with their advantages and drawbacks. MATERIALS
      AND METHODS: The PubMed database was used. Relevant search terms included 'flap'
      in combination with 'hand-held Doppler' (HHD), 'colour duplex sonography' (CDS),
      'digital subtraction angiography' (DSA), 'computed tomography angiography' (CTA)
      and 'magnetic resonance angiography' (MRA). All studies found between January
      2000 and January 2010 was evaluated. RESULTS: A total of 72 articles were found.
      Of these, 62 were usable for this overview. Recommendations could not be found
      for all types of flaps. Therefore, no uniform guidelines can be provided; some
      findings are, however, unequivocal. In general, HHD is cheap and easy to use, but
      relatively unreliable in determining the exact site of emergence at fascia level
      of perforators. CTA and MRA provide the best three-dimensional images. CTA offers
      more detailed images, MRA has the advantage however of not using radiation. CDS
      can be of value to offer information about the amount of flow in vessels or in
      cases in which CTA or MRA are contraindicated. DSA appears to be fading out
      slowly. CONCLUSION: CTA and MRA are currently the best methods available to map
      the vasculature of donor sites of perforator flaps with variable anatomy such as
      anterolateral thigh (ALT) and deep inferior epigastric perforator (DIEP). In
      flaps with standard anatomy and superficial vasculature, HHD or no mapping at all
      remains the method of choice.

PMID- 20674527
TI  - Demystifying trans-axillary augmentation/periareolar mastopexy: a novel, two
      stage, single-operation approach to management of the contralateral breast in
      implant reconstruction.
AB  - BACKGROUND: Following unilateral tissue expander/implant reconstruction, combined
      augmentation/mastopexy of the contralateral breast may be performed in an attempt
      to improve breast symmetry. Combined augmentation/mastopexy can be a very
      difficult operation, even for the surgeon with substantial experience. To
      simplify the technical approach to this complex problem, the senior author (PGC)
      has developed a 'two-stage, single-operation' approach. The purpose of this study
      is to review the safety and efficacy of this approach to the contralateral breast
      in the setting of unilateral, implant-based reconstruction. METHODS: A
      retrospective review of all combined trans-axillary augmentation/periareolar
      mastopexies performed from 1998 to 2007 was undertaken. Only patients who had a
      history of prior unilateral mastectomy and immediate expander placement were
      included. Photographic documentation of long-term aesthetic results was evaluated
      by two independent observers. RESULTS: In total, 26 combined, trans-axillary
      augmentation/periareolar mastopexies were performed in patients, who had
      initiated unilateral, postmastectomy, tissue expander/implant reconstruction on
      the contralateral side. No patient desired revisional surgery for inadequate
      ptosis correction or malpositioning of the nipple. A total of 69% of patients had
      a 'very good to excellent' overall aesthetic result. Of those patients who were
      deemed to have a 'good' aesthetic result, the development of a capsular
      contracture in the reconstructed breast detracted from the overall aesthetics.
      CONCLUSION: The two-stage, single-operation approach to unilateral
      augmentation/mastopexy described here can produce a good aesthetic result and
      allow for adequate oncologic follow-up. In particular, excellent results are seen
      in patients with grade I or II ptosis and good-quality skin preoperatively.
      Monitoring of the breast for cancer, using mammography, is still possible with
      this technique.

PMID- 20674528
TI  - Joy, struggle and support: postpartum experiences of first-time mothers in a
      Tanzanian suburb.
AB  - OBJECTIVES: To explore and describe postpartum experiences of first-time mothers
      in a Tanzanian, multiethnic, low-income suburb. METHODS: Individual qualitative
      interviews with 10 first-time mothers, 4-10 weeks postpartum in Ilala suburb, Dar
      es Salaam, Tanzania. RESULTS: The first-time mothers enjoyed motherhood and the
      respectful status it implied. To understand and handle the infant's needs and own
      bodily changes were important during postpartum. The tradition of abstaining from
      sex up to 4 years during breastfeeding was a concern as male's faithfulness was
      questioned and with HIV a threat to family health. Partner relationship changed
      towards shared parental and household work and the man's active participation was
      appreciated. Support from family members and others in the neighbourhood were
      utilised as a resource by the mothers. In instances of uncertainties on how to
      handle things, their advice was typically followed. The new mothers generally had
      good experiences of health care during the childbearing period. However, they
      also experienced insufficiencies in knowledge transfer, disrespectful behaviour,
      and unofficial fees. KEY CONCLUSIONS AND IMPLICATION FOR PRACTICE: The mothers'
      perspective of postpartum revealed that they actively searched for ways to attain
      infants' and own health needs, and family health in general. Prolonged sexual
      abstinence was considered a risk for the partner having other sexual partners and
      contracting HIV. The mothers relied heavily on the informal support network,
      which sometimes meant risking family health due to misinformation and harmful
      practices. Health care and informal support systems should complement each other
      to attain adequate support for the families postpartum.

PMID- 20674529
TI  - A comparison of school injuries between children with and without disabilities.
AB  - OBJECTIVE: The aim of this study was to compare rates, nature, and mechanisms of
      school injuries in children with and without disabilities. METHODS: We conducted
      a retrospective cohort study with repeated measures of 269 919 children with and
      without disabilities who were enrolled in 35 adapted schools from a large urban
      school district. Reports of injuries sustained from 1994 to 1998 were collected
      by the district's insurance division, and disability was assessed using special
      education guidelines determined by the California Department of Education. A
      generalized estimating equations model was used to estimate rate ratios,
      accounting for the repeated, nested nature of the data. RESULTS: Children with
      disabilities had more than double the rate of injury reported than children
      without disabilities (incidence density ratio [IDR] 2.3, 95% CI, 2.2-2.5). Almost
      one third of these injuries were due to fights, roughhousing, and assaults. Among
      all disabled children, those with orthopedic disabilities had the highest risk,
      with rates over 5 times that of children without disabilities (IDR 5.4, 95% CI,
      4.4-6.6). Children with cognitive disabilities had comparatively lower rates of
      injury than children with physical disabilities. CONCLUSIONS: For children with
      disabilities, physical impairment may play a greater role than cognitive
      impairment in managing risk for injury at school. Individual education programs
      (IEP), developed for children in special education, could be tailored to include
      injury prevention strategies.

PMID- 20674530
TI  - Adolescent fighting: racial/ethnic disparities and the importance of families and
      schools.
AB  - OBJECTIVE: To identify factors associated with fighting among African American,
      Asian/Pacific Islander, Latino, and white youth, with a focus on family and
      school connectedness. METHODS: Subjects were 4010 adolescents (12-17 years old)
      from the 2003 California Health Interview Survey. Stratified logistic regression
      examined whether fighting in the past year was associated with various risk and
      protective factors among African American, Asian/Pacific Islander, Latino, and
      white youth subsamples. RESULTS: Fighting was reported by 27% of African
      American, 24% of Latino, 16% of white, and 6% of Asian/Pacific Islander youth.
      Male gender, alcohol use, and smoking were associated with higher odds of
      fighting among whites and Latinos. Poverty was associated with higher odds of
      fighting among whites and African Americans, as was depression among Latinos.
      Higher family support was associated with decreased odds of fighting for white
      youth. Higher school support was associated with decreased odds of fighting for
      Latino youth. CONCLUSIONS: A higher proportion of African American and Latino
      youth report fighting than do whites and Asians/Pacific Islanders. There is,
      however, important variation in racial/ethnic disparities in risk and protective
      factors associated with fighting. Family and school factors may be protective
      against fighting. Prevention and intervention efforts to decrease youth violence
      might benefit from tailoring to communities' racial/ethnic composition and paying
      greater attention to family and community influences on adolescent fighting.

PMID- 20674531
TI  - The ripples of adolescent motherhood: social, educational, and medical outcomes
      for children of teen and prior teen mothers.
AB  - OBJECTIVE: We examined medical, educational and social risks to children of teen
      mothers and children of nonadolescent mothers with a history of teen birth (prior
      teen mothers) and considered these risks at both the individual and societal
      level. METHODS: A population-based, retrospective cohort study tracked outcomes
      through young adulthood for children born in Manitoba, Canada (n = 32 179).
      chi(2) and logistic regression analyses examined risk of childhood death or
      hospitalization, failure to graduate high school, intervention by child
      protective services, becoming a teen mother, and welfare receipt as a young
      adult. RESULTS: For children of both teen and prior teen mothers, adjusted
      likelihoods of death during infancy, school-aged years, and adolescence were more
      than 2-fold higher than for other children. Risks for hospitalization, high
      hospital use, academic failure, and poor social outcomes were also substantially
      higher. At a societal level, only 16.5% of cohort children were born to teen and
      prior teen mothers. However, these children accounted for 27% of first-year
      hospitalizations, 34% of deaths (birth to 17 years), 30% of failures to graduate
      high school, 51% in foster care, 44% on welfare as young adults, and 56% of next
      generation young teen mothers. CONCLUSIONS: Children of prior teen mothers had
      increased risks for poor health and for educational and social outcomes nearly
      equal to those seen in children of teen mothers. Combined, these relatively few
      children experienced a large share of the negative outcomes occurring among young
      people. Our results suggest the need to expand the definition of risk associated
      with adolescent motherhood and target their children for enhanced medical and
      social services.

PMID- 20674532
TI  - Parental understanding of infant health information: health literacy, numeracy,
      and the Parental Health Literacy Activities Test (PHLAT).
AB  - OBJECTIVE: To assess parental health literacy and numeracy skills in
      understanding instructions for caring for young children, and to develop and
      validate a new parental health literacy scale, the Parental Health Literacy
      Activities Test (PHLAT). METHODS: Caregivers of infants (age <13 months) were
      recruited in a cross-sectional study at pediatric clinics at 3 academic medical
      centers. Literacy and numeracy skills were assessed with previously validated
      instruments. Parental health literacy was assessed with the new 20-item PHLAT.
      Psychometric analyses were performed to assess item characteristics and to
      generate a shortened, 10-item version (PHLAT-10). RESULTS: A total of 182
      caregivers were recruited. Although 99% had adequate literacy skills, only 17%
      had better than ninth-grade numeracy skills. Mean score on the PHLAT was 68%
      (standard deviation 18); for example, only 47% of caregivers could correctly
      describe how to mix infant formula from concentrate, and only 69% could interpret
      a digital thermometer to determine whether an infant had a fever. Higher
      performance on the PHLAT was significantly correlated (P < .001) with education,
      literacy skill, and numeracy level (r = 0.29, 0.38, and 0.55 respectively).
      Caregivers with higher PHLAT scores were also more likely to interpret age
      recommendations for cold medications correctly (odds ratio 1.6, 95% confidence
      interval 1.02, 2.6). Internal reliability on the PHLAT was good (Kuder-Richardson
      coefficient of reliability = 0.76). The PHLAT-10 also demonstrated good validity
      and reliability. CONCLUSIONS: Many parents do not understand common health
      information required to care for their infants. The PHLAT and PHLAT-10 have good
      reliability and validity and may be useful tools for identifying parents who need
      better communication of health-related instructions.

PMID- 20674533
TI  - Impact of different types of walking aids on the physiological energy cost during
      gait for elderly individuals with several pathologies and dependent on a
      technical aid for walking.
AB  - In elderly individuals balance disorders and muscle weakness can lead to
      prescribing a walker. There are several different models. According to the very
      poor effort tolerance in this population, the energy cost necessary to operate
      walking technical aids should be taken into account when making a choice.
      OBJECTIVE: Compare two types of walker in regards to energy cost produced during
      gait in weakened elderly individuals. METHOD: Thirty subjects over the age of 65
      (six men and 24 women, mean age 81.9 years) were admitted in geriatrics care.
      They all required a walker and performed the same 10-m course with a fixed
      walker, then with a model bearing front wheels. The walking speed (S) was
      computed, heart rate at rest (HRrest) and maximum heart rate (HRmax) were
      recorded during the test. The physiological cost index (PCI=HRmax-HRrest/S) was
      calculated. Finally a timed get-up-and-go (TGUG) test was performed with each of
      these technical aids. RESULTS: With a rollator walker, HRmax was lower (P<0.05)
      and S higher (P<0.001). It was 2.01 with a fixed walker versus 1.23 with a
      rollator walker (P<0.01). We found this speed difference during the TGUG test
      (72.26 sec vs. 82.93 sec, P=0.001). DISCUSSION AND CONCLUSION: There are very
      little studies on the evaluation of physiological energy cost produced during
      gait with a walker. The characteristics of our population did not allow us to
      conduct our test without a technical aid. The use of a fixed walker leads to a
      major increase in gait PCI, probably due to the required repeated efforts for
      lifting the walker. This model must be avoided in case of cardiac or respiratory
      disorders.

PMID- 20674534
TI  - Gait initiation reflects the adaptive biomechanical strategies of adolescents
      with idiopathic scoliosis.
AB  - BACKGROUND: The dynamics behavior of patients with idiopathic scoliosis obviously
      requires some biomechanical compensatory strategies. Our objective is to analyze
      the ground reaction forces (GRF) exerted during gait initiation in order to
      determine the dynamic consequences of idiopathic scoliosis. METHODS: Ten
      adolescent girls suffering from idiopathic scoliosis with a right thoracic
      curvature (Cobb>15 degrees ) and 15 healthy adolescents participated in this
      study. Two force plates were used to record the ground force evolution for the
      right and left limbs tested during gait initiation. RESULTS: Whichever limb was
      used to initiate gait, gait initiation duration was found to be significantly
      longer in persons with scoliosis than in healthy subjects. In the scoliosis group
      (SG), the impulses, occurrences and forces values were also greater than in
      healthy subjects. Under the stance foot, the anteroposterior and vertical forces
      were always increased. Under the swing foot, the SG showed the same
      characteristics associated to decreased mediolateral impulses parameters. Even
      greater differences were observed between these two groups in terms of peak
      occurrences during left-limb gait initiation. The intragroup comparisons only
      unveiled very few differences between the two limbs for the control group (CG),
      whereas significantly higher values were recorded for the group of scoliosis
      patients when gait was initiated with the left limb rather than with the right
      one. CONCLUSION: For patients with scoliosis specific dynamic behavior adjustment
      are made during gait initiation patterns, for both limbs in order to maintain
      balance during gait to compensate for their spine deformation. Patients with
      scoliosis always showed slower dynamic patterns than healthy controls. These
      results show the importance of including specific evaluation and dynamic physical
      rehabilitation for patients with idiopathic scoliosis.

PMID- 20674535
TI  - Characteristics and survival associated with ovarian cancer diagnosed as first
      cancer and ovarian cancer diagnosed subsequent to a previous cancer.
AB  - OBJECTIVE: To examine the risk of subsequent primary ovarian cancer among women
      diagnosed previously with cancer (subsequent cohort) and to compare demographic
      and tumor characteristics affecting overall survival of these women and women
      diagnosed with first primary ovarian cancer (index cohort). METHODS: We
      identified the two cohorts of women using the 1973-2005 Surveillance,
      Epidemiology and End Results (SEER) result data. We calculated relative risk of
      subsequent primary ovarian cancer and estimated 5-year risks of dying (hazard
      ratios) after diagnosis of the first or subsequent primary ovarian cancer in the
      two cohorts, respectively using Cox modeling. RESULTS: Women diagnosed with index
      cancers of the corpus uteri, colon, cervix, and melanoma at age younger than 50
      had increased risk of ovarian cancer within 5 years after diagnosis (p<0.05);
      young breast cancer survivors had continued risk beyond 20 years. In 5-year
      follow-up survival analysis, the factors associated with a better survival
      (p<0.05) were similar in both cohorts and included more recent diagnosis;
      localized or regional disease; age <50 years at diagnosis; and being white versus
      black. A lower risk of dying from mucinous, endometrioid, or non-epithelial
      tumors than from serous was seen after 15 months (p<0.01), or after 32 months
      from diagnosis of the index and subsequent cohorts, respectively. CONCLUSIONS:
      Age, stage, and histology affect ovarian cancer survival. The increased risk of
      ovarian cancer over time, especially among breast and colon cancer survivors who
      are less than 50 years of age, suggests common etiologies and necessitates
      careful surveillance by health care providers and increased survivors awareness
      through educational efforts.

PMID- 20674536
TI  - Childhood cancer survival: a report from the United Kingdom Childhood Cancer
      Study.
AB  - BACKGROUND: Improvements in diagnostic approaches and refinements to treatment
      protocols have resulted in 5-year survival levels above 70% for children
      diagnosed with cancer in economically developed parts of the world. For some
      cancers, including leukaemia and tumours of the central nervous system, age and
      sex have been identified as important prognostic indicators. METHODS: We examined
      long-term survival, and affects of age and sex, in a population-based case
      control study. Children (0-14 years) newly diagnosed with cancer were ascertained
      between 1991 and 1996 (n=4433). Follow-up information was obtained from the
      National Health Service (NHS) Information Centre for Health and Social Care which
      records all exits from the NHS including deaths. RESULTS: For all cancer
      diagnoses combined, 5-year survival was 72.7% dropping to 67.9% at 15 years. As
      expected, survival differed between diagnostic subtypes ranging from 38.1% for
      intracranial embryonal tumours to 96.2% for Hodgkin lymphoma. Compared to girls,
      boys diagnosed with acute lymphoblastic leukaemia were at a higher risk of dying
      (RR=1.26, 95% CI 1.03-1.53), whereas boys diagnosed with an intracranial
      embryonal tumour were at a lower risk of death (RR=0.63, 95% CI 0.43-0.91).
      CONCLUSION: Our initial findings are consistent with previous reports, and
      highlight the importance of considering differences by age and sex. The
      completeness and population-based nature of the original case-control study is an
      important feature which will provide the basis for future more detailed
      investigations linking disease determinants to outcome.

PMID- 20674537
TI  - Primary exploration of CDR3 spectratyping and molecular features of TCR beta
      chain in the peripheral blood and tissue of patients with colorectal carcinoma.
AB  - BACKGROUND: The immunoscope spectratyping to TRBV CDR3 had been applied in
      infectious diseases, tumors, autoimmune diseases and so on, this study aimed to
      primarily explore CDR3 spectratyping and molecular features of TCR beta chain in
      the peripheral blood and tissue of patients with colorectal carcinoma. METHODS:
      Blood and tissue samples were collected from seven patients with colorectal
      carcinoma (CRC), while blood samples were also collected from two healthy
      controls as control. Using the real-time fluorescence quantitative reverse
      transcription polymerase chain reaction (RQ-PCR) and DNA melting curve analysis
      techniques, the features of T-cell receptor beta chain variable region (TRBV)
      were determined. RESULTS: The gene melting spectral pattern (GMSP) of 24 TRBV
      gene families exhibited a highly diverse multimodal shape for most of the TRBV
      gene families, compared to healthy controls, the more GMSP of patients with CRC
      showed either a single peak, or several prominent melting peaks (skewed) for
      certain TRBV gene families. Different patients have different skewed patterns. In
      the analysis results of sequence, some TRBV CDR3 gene families showed sharing the
      same motif, such as, TRBV6 of P5, TRBV13.1 of P6 and TRBV21 of P7 (tissue sample)
      shared the same motif 'GT'; TRBV1 of P1 and TRBV21 of P7 shared the same motif
      'AGG', TRBV11 of P1, TRBV21 of P5 and TRBV21 of P7 (tissue sample) shared the
      same motif 'TDTQY', and even TRBV21 of P5 and P7 (tissue sample) shared the large
      motif 'SGTDTQY'. As a whole, most of TRBV gene families have the similar motifs
      'X-Q', the nucleotide 'X' mainly was 'E', it also was possible be 'T', 'G' or 'K'
      in some CDR3 gene families of patients with CRC. CONCLUSIONS: There were
      different GMSPs in different patients with CRC, CDR3 spectratyping and the
      molecular features of TCR beta chain in the peripheral blood and tissue of
      patients with CRC were not same or similar, this information would provide ideas
      for individualized therapy to CRC.

PMID- 20674538
TI  - Incidence of cancer in kidney-transplant recipients: a long-term cohort study in
      a single center.
AB  - In a long-term cohort study, we calculated cancer incidences and survival rates
      after the development of these cancers in kidney-transplant recipients. The
      cancer incidences were compared with those in the general population. The
      occurrence of cancer was recorded in all patients who received kidney
      transplantation between 1966 and 2006. The median follow-up time was more than 9
      years with a maximum of almost 40 years. Altogether 327 (17%) of 1906 patients
      developed cancer after transplantation: 142 (7%) had non-cutaneous malignancies;
      178 (9%) cutaneous squamous-cell carcinomas and 138 (7%) basal-cell carcinomas.
      The cumulative incidence of any cancer was 13%, 33% and 47% after 10, 20 and 30
      years, respectively. The incidences of cancers of the oral cavity, stomach,
      female genital organs, kidney, thyroid gland, leukemias and lymphomas, and
      cutaneous squamous-cell carcinoma were significantly increased with a highest
      standardized morbidity ratio of 40 for cutaneous squamous-cell carcinomas.
      Survival rates after non-cutaneous malignancies were 57%, 43% and 36% and after
      non-melanocytic skin cancer 99%, 90% and 77% after 1, 3 and 5 years,
      respectively. The increased incidence of non-cutaneous malignancies after kidney
      transplantation is associated with a high mortality. Prevention of cancer after
      kidney transplantation should be a major focus of future research.

PMID- 20674539
TI  - A diacylglycerol-dependent signaling pathway contributes to regulation of
      antibacterial autophagy.
AB  - Autophagy mediates the degradation of cytoplasmic contents in the lysosome and
      plays a significant role in immunity. Lipid second messengers have previously
      been implicated in the regulation of autophagy. Here, we demonstrate a signaling
      role for diacylglycerol (DAG) in antibacterial autophagy. DAG production was
      necessary for efficient autophagy of Salmonella, and its localization to bacteria
      containing phagosomes preceded autophagy. The actions of phospholipase D and
      phosphatidic acid phosphatase were required for DAG generation and autophagy.
      Furthermore, the DAG-responsive delta isoform of protein kinase C was required,
      as were its downstream targets JNK and NADPH oxidase. Previous studies have
      revealed a role for the ubiquitin-binding adaptor molecules p62 and NDP52 in
      autophagy of S. Typhimurium. We observed bacteria-containing autophagosomes
      colocalizing individually with either DAG or ubiquitinated proteins, indicating
      that both signals can act independently to promote antibacterial autophagy. These
      findings reveal an important role for DAG-mediated PKC function in mammalian
      antibacterial autophagy.

PMID- 20674541
TI  - Electrostatic interaction in the NH(2)-terminus accelerates inactivation of the
      Kv1.4 channel.
AB  - Inactivation of potassium channels plays an important role in shaping the
      electrical signalling properties of nerve and muscle cells. While it has been
      assumed that the rapid inactivation of the Kv1.4 channel is controlled by a "ball
      and chain" inactivation mechanism, the chain structure of the channel has not
      been well defined. Here, by conducting electrophysiological studies on variants
      containing mutations of the positively charged and negatively charged segments of
      the NH(2)-terminal of the channel protein, we show that neutralization or
      deletion of the positively charged segment (residues 83-98) significantly slowed
      the inactivation process. Replacement of this positively charged segment with the
      negatively charged segment (residues 123-137), and vice versa, so that both
      segments were simultaneously positively or negatively charged, also slowed the
      inactivation process. Furthermore, the inactivation process was not changed when
      the positively charged and the negatively charged segments were interchanged. In
      contrast, the voltage dependence of activation and inactivation of the channels
      was not significantly altered by these mutants. These results indicate that the
      electrostatic interaction between the positively and negatively charged segments
      plays a critical role in the inactivation process of the Kv1.4 channel. Taken
      together, we propose that the electrostatic interaction accelerates the
      inactivation of the Kv1.4 channel by making it easier for the inactivation ball
      to access its binding site.

PMID- 20674540
TI  - The aryl hydrocarbon receptor nuclear translocator-interacting protein 2
      suppresses the estrogen receptor signaling via an Arnt-dependent mechanism.
AB  - We explored whether modulation of the estrogen receptor (ER) signaling is
      possible through an aryl hydrocarbon receptor nuclear translocator (Arnt)
      dependent mechanism. We utilized the Arnt-interacting protein 2 (Ainp2) to
      examine whether the presence of Ainp2 in MCF-7 cells would interfere with the
      Arnt-mediated ER signaling. We found that Arnt increased the 17 beta-estradiol
      (E2)-dependent luciferase activity and Ainp2 significantly suppressed this Arnt
      mediated luciferase activity. Ainp2 significantly suppressed 25% of the E2- and
      Arnt-dependent up-regulation of the GREB1 message. No suppression of the ER
      target gene expression by Ainp2 was detected in Arnt-knockdown MCF-7 cells and in
      Arnt-independent ER signaling. Although Ainp2 did not interact with ER alpha and
      ER beta, it suppressed the ER alpha::Arnt interaction and reduced the E2-driven
      recruitment of Arnt to the GREB1 promoter. We concluded that Ainp2 suppresses the
      ER signaling by not allowing Arnt to participate in the ER-dependent, Arnt
      mediated activation of gene transcription.

PMID- 20674542
TI  - Plasma membrane sterol complexation, generated by filipin, triggers signaling
      responses in tobacco cells.
AB  - The effects of changes in plasma membrane (PM) sterol lateral organization and
      availability on the control of signaling pathways have been reported in various
      animal systems, but rarely assessed in plant cells. In the present study, the
      pentaene macrolide antibiotic filipin III, commonly used in animal systems as a
      sterol sequestrating agent, was applied to tobacco cells. We show that filipin
      can be used at a non-lethal concentration that still allows an homogeneous
      labeling of the plasma membrane and the formation of filipin-sterol complexes at
      the ultrastructural level. This filipin concentration triggers a rapid and
      transient NADPH oxidase-dependent production of reactive oxygen species, together
      with an increase in both medium alkalinization and conductivity. Pharmacological
      inhibition studies suggest that these signaling events may be regulated by
      phosphorylations and free calcium. By conducting FRAP experiments using the di-4
      ANEPPDHQ probe and spectrofluorimetry using the Laurdan probe, we provide
      evidence for a filipin-induced increase in PM viscosity that is also regulated by
      phosphorylations. We conclude that filipin triggers ligand-independent signaling
      responses in plant cells. The present findings strongly suggest that changes in
      PM sterol availability could act as a sensor of the modifications of cell
      environment in plants leading to adaptive cell responses through regulated
      signaling processes.

PMID- 20674543
TI  - A synopsis of the process of lipid peroxidation since the discovery of the
      essential fatty acids.
AB  - Eighty years ago, Burr and Burr, introduced for the first time the concept of
      essential fatty acids. Now is very well known that requirements for
      polyunsaturated fatty acids PUFAs can not be met by de novo metabolic processes
      within mammalian tissues. Animals are absolutely dependent on plants for
      providing the two major precursors of the n-6 and n-3 fatty acids, C18:2n-6;
      linoleic and C18:3n-3; alpha-linolenic acids. In animal tissues these precursors
      are transformed to fatty acids containing three to six double bonds. During the
      last four decades the interest in polyunsaturated fatty acids has augmented
      manifolds, and the number of published studies is rising each year. The current
      impetus for this interest has been mainly the observation that PUFAs and their
      metabolites have several physiological roles including: energy provision,
      membrane structure, cell signaling and regulation of gene expression. In addition
      the observation that PUFAs are targets of lipid peroxidation opens a new
      important area of investigation. Melatonin, the main secretory product of the
      pineal gland, efficiently scavenges both the hydroxyl and peroxyl radicals
      counteracting lipid peroxidation in biological membranes. In addition the two key
      pineal biochemical functions, lipoxygenation and melatonin synthesis may be
      synergistically regulated by the status of n-3 essential fatty acids. At the
      retina level, free radicals may preferentially react with the membrane
      polyunsaturated fatty acids leading to the release of lipoperoxide radicals.
      These lipoperoxides can induce oxidative stress linked to membrane lysis, damage
      to neuronal membranes may be related to alteration of visual function.

PMID- 20674544
TI  - Structural motifs are closed into cycles in proteins.
AB  - Beta-hairpins, triple-strand beta-sheets and betaalphabeta-units represent simple
      structural motifs closed into cycles by systems of hydrogen bonds. Secondary
      closing of these simple motifs into large cycles by means of different
      superhelices, split beta-hairpins or SS-bridges results in the formation of more
      complex structural motifs having unique overall folds and unique handedness such
      as abcd-units, phi-motifs, five- and seven-segment alpha/beta-motifs. Apparently,
      the complex structural motifs are more cooperative and stable and this may be one
      of the main reasons of high frequencies of occurrence of the motifs in proteins.

PMID- 20674545
TI  - Critical role for the catalytic activity of phospholipase C-gamma1 in epidermal
      growth factor-induced cell migration.
AB  - Phospholipase C-gamma1 (PLC-gamma1), a tyrosine kinase substrate, has been
      implicated in the pathway for the epidermal growth factor receptor (EGFR)-induced
      cell migration. However, the underlying mechanism by which PLC-gamma1 mediates
      EGFR-induced cell migration remains elusive. In the present study, we sought to
      determine whether the lipase activity of PLC-gamma1 is required for EGFR-induced
      cell migration. We found that overexpression of PLC-gamma1 in squamous cell
      carcinoma SCC4 cells markedly enhanced EGF-induced PLC-gamma1 activation,
      intracellular calcium rise, and cell migration. This enhancement was abolished by
      mutational inactivation of the catalytic domain of PLC-gamma1. Inhibition of the
      downstream signaling processes mediated by the activity of phospholipase C (PLC)
      using IP(3) receptor inhibitor or intracellular calcium chelator blocked EGF
      induced cell migration. These data indicate that EGF-induced cell migration is
      mediated by the lipase domain of PLC-gamma1 and the subsequent IP(3) generation
      and intracellular calcium mobilization.

PMID- 20674546
TI  - COPI-mediated retrograde trafficking from the Golgi to the ER regulates EGFR
      nuclear transport.
AB  - Emerging evidence indicates that cell surface receptors, such as the entire
      epidermal growth factor receptor (EGFR) family, have been shown to localize in
      the nucleus. A retrograde route from the Golgi to the endoplasmic reticulum (ER)
      is postulated to be involved in the EGFR trafficking to the nucleus; however, the
      molecular mechanism in this proposed model remains unexplored. Here, we
      demonstrate that membrane-embedded vesicular trafficking is involved in the
      nuclear transport of EGFR. Confocal immunofluorescence reveals that in response
      to EGF, a portion of EGFR redistributes to the Golgi and the ER, where its NH(2)
      terminus resides within the lumen of Golgi/ER and COOH-terminus is exposed to the
      cytoplasm. Blockage of the Golgi-to-ER retrograde trafficking by brefeldin A or
      dominant mutants of the small GTPase ADP-ribosylation factor, which both resulted
      in the disassembly of the coat protein complex I (COPI) coat to the Golgi,
      inhibit EGFR transport to the ER and the nucleus. We further find that EGF
      dependent nuclear transport of EGFR is regulated by retrograde trafficking from
      the Golgi to the ER involving an association of EGFR with gamma-COP, one of the
      subunits of the COPI coatomer. Our findings experimentally provide a
      comprehensive pathway that nuclear transport of EGFR is regulated by COPI
      mediated vesicular trafficking from the Golgi to the ER, and may serve as a
      general mechanism in regulating the nuclear transport of other cell surface
      receptors.

PMID- 20674547
TI  - RAF protein-serine/threonine kinases: structure and regulation.
AB  - A-RAF, B-RAF, and C-RAF are a family of three protein-serine/threonine kinases
      that participate in the RAS-RAF-MEK-ERK signal transduction cascade. This cascade
      participates in the regulation of a large variety of processes including
      apoptosis, cell cycle progression, differentiation, proliferation, and
      transformation to the cancerous state. RAS mutations occur in 15-30% of all human
      cancers, and B-RAF mutations occur in 30-60% of melanomas, 30-50% of thyroid
      cancers, and 5-20% of colorectal cancers. Activation of the RAF kinases requires
      their interaction with RAS-GTP along with dephosphorylation and also
      phosphorylation by SRC family protein-tyrosine kinases and other protein
      serine/threonine kinases. The formation of unique side-to-side RAF dimers is
      required for full kinase activity. RAF kinase inhibitors are effective in
      blocking MEK1/2 and ERK1/2 activation in cells containing the oncogenic B-RAF
      Val600Glu activating mutation. RAF kinase inhibitors lead to the paradoxical
      increase in RAF kinase activity in cells containing wild-type B-RAF and wild-type
      or activated mutant RAS. C-RAF plays a key role in this paradoxical increase in
      downstream MEK-ERK activation.

PMID- 20674548
TI  - Identification of BMP-responsive elements in the mouse Id2 gene.
AB  - Inhibitor of DNA binding/differentiation (Id) genes are the targets of bone
      morphogenetic protein (BMP) signals in various types of cells. We investigated
      the molecular basis of BMP6-induced gene expression of mouse Id2 in C2C12
      myoblasts. BMP6-dependent Id2 expression occurred immediately without de novo
      protein synthesis and was blocked by an inhibitor of the BMP type I receptors. A
      reporter assay identified a BMP6-responsive region 3.0kb upstream of the
      transcription initiation site. The region showed sequence similarity to the mouse
      Id1 promoter and shared potential Smad binding sites with it, two GGCGCC
      palindromes and one GTCT element. Mutation analysis demonstrated the involvement
      of these elements in the BMP response. Gel shift and chromatin
      immunoprecipitation (ChIP) assays confirmed the physical binding of Smad proteins
      to these elements. The 3'-positioned GGCGCC palindrome and the GTCT element were
      separated by 5-bp and conformed to the canonical BMP-responsive sequence. In
      addition, the 5'-positioned GGCGCC was accompanied by a previously
      uncharacterized CGCC element, which were separated by a 5-bp space, and this
      configuration coincided with that of a similar but distinct sequence to which a
      Drosophila homolog of the Smad complex can bind. Reporter and gel shift assays
      revealed the importance of this bipartite sequence. Therefore, we have identified
      the BMP-responsive elements in mouse Id2 and also shown that the CGCC sequence
      contributes to target recognition by Smad proteins.

PMID- 20674549
TI  - Red cell PMVs, plasma membrane-derived vesicles calling out for standards.
AB  - Plasma membrane-derived vesicles (PMVs) or microparticles are vesicles (0.1-1mum
      in diameter) released from the plasma membrane of all blood cell types under a
      variety of biochemical and pathological conditions. PMVs contain cytoskeletal
      elements and some surface markers from the parent cell but lack a nucleus and are
      unable to synthesise macromolecules. They are also defined on the basis that in
      most cases PMVs express varying amounts of the cytosolic leaflet lipid
      phosphatidylserine, which is externalised during activation on their surface.
      This marks the PMV as a biologically distinct entity from that of its parent
      cell, despite containing surface markers from the original cell, and also
      explains its role in events such as phagocytosis and thrombosis. There is
      currently a large amount of variation between investigators with regard to the
      pre-analytical steps employed in isolating red cell PMVs or RPMVs (which are
      slightly smaller than most PMVs), with key differences being centrifugation and
      sample storage conditions, which often leads to result variability.
      Unfortunately, standardization of preparation and detection methods has not yet
      been achieved. This review highlights and critically discusses the variables
      contributing to differences in results obtained by investigators, bringing to
      light numerous studies of which RPMVs have been analysed but have not yet been
      the subject of a review.

PMID- 20674550
TI  - Genome-to-function characterization of novel fungal P450 monooxygenases oxidizing
      polycyclic aromatic hydrocarbons (PAHs).
AB  - Fungi, particularly the white rot basidiomycetes, have an extraordinary
      capability to degrade and/or mineralize (to CO(2)) the recalcitrant fused-ring
      high molecular weight (4 aromatic-rings) polycyclic aromatic hydrocarbons (HMW
      PAHs). Despite over 30years of research demonstrating involvement of P450
      monooxygenation reactions in fungal metabolism of HMW PAHs, specific P450
      monooxygenases responsible for oxidation of these compounds are not yet known.
      Here we report the first comprehensive identification and functional
      characterization of P450 monooxygenases capable of oxidizing different ring-size
      PAHs in the model white rot fungus Phanerochaete chrysosporium using a successful
      genome-to-function strategy. In a genome-wide P450 microarray screen, we
      identified six PAH-responsive P450 genes (Pc-pah1-Pc-pah6) inducible by PAHs of
      varying ring size, namely naphthalene, phenanthrene, pyrene, and benzo(a)pyrene
      (BaP). Using a co-expression strategy, cDNAs of the six Pc-Pah P450s were cloned
      and expressed in Pichia pastoris in conjunction with the homologous P450
      oxidoreductase (Pc-POR). Each of the six recombinant P450 monooxygenases showed
      PAH-oxidizing activity albeit with varying substrate specificity towards PAHs (3
      5 rings). All six P450s oxidized pyrene (4-ring) into two monohydroxylated
      products. Pc-Pah1 and Pc-Pah3 oxidized BaP (5-ring) to 3-hydroxyBaP whereas Pc
      Pah4 and Pc-Pah6 oxidized phenanthrene (3-ring) to 3-, 4-, and 9-phenanthrol.
      These PAH-oxidizing P450s (493-547 aa) are structurally diverse and novel
      considering their low overall homology (12-23%) to mammalian counterparts. To our
      knowledge, this is the first report on specific fungal P450 monooxygenases with
      catalytic activity toward environmentally persistent and highly toxic HMW PAHs.

PMID- 20674551
TI  - Treatment of PCR products with exonuclease I and heat-labile alkaline phosphatase
      improves the visibility of combined bisulfite restriction analysis.
AB  - DNA methylation plays a vital role in the regulation of gene expression. Abnormal
      promoter hypermethylation is an important mechanism of inactivating tumor
      suppressor genes in human cancers. Combined bisulfite restriction analysis
      (COBRA) is a widely used method for identifying the DNA methylation of specific
      CpG sites. Here, we report that exonuclease I and heat-labile alkaline
      phosphatase can be used for PCR purification for COBRA, improving the visibility
      of gel electrophoresis after restriction digestion. This improvement is observed
      when restriction digestion is performed at a high temperature, such as 60 degrees
      C or 65 degrees C, with BstUI and TaqI, respectively. This simple method can be
      applied instead of DNA purification using spin columns or phenol/chloroform
      extraction. It can also be applied to other situations when PCR products are
      digested by thermophile-derived restriction enzymes, such as PCR restriction
      fragment length polymorphism (RFLP) analysis.

PMID- 20674552
TI  - Bovine binder-of-sperm protein BSP1 promotes protrusion and nanotube formation
      from liposomes.
AB  - Binder-of-sperm (BSP) proteins interact with sperm membranes and are proposed to
      extract selectively phosphatidylcholine and cholesterol from these. This change
      in lipid composition is a key step in sperm capacitation. The present work
      demonstrates that the interactions between the protein BSP1 and model membranes
      composed with phosphatidylcholine lead to drastic changes in the morphology of
      the lipidic self-assemblies. Using cryo-electron microscopy and fluorescence
      microscopy, we show that, in the presence of the protein, the lipid vesicles
      elongate, and form bead necklace-like structures that evolve toward small
      vesicles or thread-like structures. In the presence of multilamellar vesicles,
      where a large reservoir of lipid is available, the presence of BSP proteins lead
      to the formation of long nanotubes. Long spiral-like threads, associated with
      lipid/protein complexes, are also observed. The local curvature of lipid
      membranes induced by the BSP proteins may be involved in lipid domain formation
      and the extraction of some lipids during the sperm maturation process.

PMID- 20674553
TI  - Inhibition of cell growth and potentiation of tumor necrosis factor-alpha (TNF
      alpha)-induced apoptosis by a phenanthroindolizidine alkaloid antofine in human
      colon cancer cells.
AB  - Based on the potential of natural products as a source for the development of
      cancer chemotherapeutic agents, this study was performed to investigate the anti
      proliferative and antitumor effects of antofine, a phenanthroindolizidine
      alkaloid derived from Cynanchum paniculatum. Antofine showed potent anti
      proliferative effects in several human cancer cells with IC(50) values in the
      nanomolar range. Treatment with antofine for 24h did not result in the induction
      of apoptotic cell death but moderately induced cell cycle arrest at G0/G1 phase
      and inhibited the expression of cyclin D1, cyclin E, and CDK4. In addition,
      antofine inhibited the transcriptional activity of beta-catenin/Tcf in human
      colon HCT 116 cells, and the expression level of beta-catenin and cyclin D1 was
      also down-regulated by antofine in human colon SW480 cells. Moreover, antofine
      potentiated tumor necrosis factor-alpha (TNF-alpha)-induced apoptosis, which was
      demonstrated by the increase of Annexin V-positive cell population and of the
      cleavage of poly (ADP-ribose) polymerase (PARP) and caspase-8. Antofine also
      effectively suppressed tumor growth in the HCT 116 implanted xenograft nude mouse
      model. Taken together, these findings suggest that antofine might be a potential
      candidate for the development of cancer chemotherapeutic agents derived from
      natural products.

PMID- 20674554
TI  - The neural mechanisms of reciprocal communication.
AB  - Imitation in humans has been attributed to increased activation of the mirror
      neuron system, but there is no neural model to explain reciprocal communication.
      In this study, we investigated whether reciprocal, communicative, imitative
      exchanges activate the same neural system as imitation of simple movements, and
      whether the neural network subserving communication is lateralized. Fifteen
      participants were tested using functional magnetic resonance imaging with an
      online interactive-imitative paradigm while they performed finger movements for
      three different purposes: (1) to imitate the experimenter, (2) to elicit an
      imitation from the experimenter, and (3) to simply perform the movement.
      Subtraction analysis (imitation > movement, initiation > movement) revealed the
      activation of a strongly lateralized network, where the infra-parietal lobule
      (IPL) activation was lateralized to the left, while the infero-frontal gyrus
      (IFG) activation was to the right. It is concluded that imitation in a
      communicative paradigm recruits a lateralized network, with left fronto- and
      right parietal activation, that overlaps with a network that subserves
      understanding of an Other's intentions in relation to the Self. This finding
      lends plausibility to the suggestion that the neural network for imitation
      evolved to support interpersonal communication.

PMID- 20674555
TI  - Crossmodal congruency effects based on stimulus identity.
AB  - We investigated whether the crossmodal congruency effect, normally observed in
      spatial compatibility tasks, would also affect performance on a task based on
      discriminating stimulus identity (i.e., a non-spatial dimension). Two rhythms
      were presented to participants' eyes, ears, and/or hands in a 4-alternative
      rhythm discrimination task. Stimulus identity and stimulus modality were varied
      orthogonally. When the target and distractor rhythms were presented in different
      sensory modalities, significant crossmodal congruency effects were observed in
      all conditions (i.e., performance on the incongruent distractor trials was
      significantly more error-prone than on the congruent distractor trials). In
      contrast to the results of previous studies, these crossmodal distractor effects
      were neither based on the spatial compatibility of the stimuli nor on an abstract
      semantic matching of stimulus identity, but instead on the identity of the target
      rhythm. Intriguingly, the magnitude of the crossmodal congruency effects differed
      as a function of the target modality, but were unaffected by the modality of the
      distractor.

PMID- 20674556
TI  - Alterations in the brain electrical activity in a rat model of sepsis-associated
      encephalopathy.
AB  - Sepsis and septic shock are the commonest causes of death in the intensive care
      units. Although recent research have improved our understanding of the progress
      and pathophysiology of sepsis and septic shock, underlying mechanisms in sepsis
      associated encephalopathy is still poorly understood. The incidence of sepsis
      associated encephalopathy has been reported to vary from 8% to 70% of septic
      patients. We aimed at investigating the brain's electrical activity using
      somatosensory-evoked potentials and electrocorticographical recordings in cecal
      ligation and puncture rat model of sepsis. Significant decrease in mean arterial
      pressure, increase in heart rate, deteriorated neurological reflexes together
      with positive blood cultures results, thrombocytopenia and increased blood
      lactate levels suggesting the successful induction of sepsis in the present
      study. Elongated latencies and increased amplitudes were observed in
      somatosensory recordings of septic group, while electrocorticograms revealed
      slight decrease in median and spectral edge frequencies amplitudes and
      significantly increased delta activities in 50% of the septic rats. These results
      would suggest that the studies based on the investigation of the sepsis
      associated encephalopathy in animal models needs to be combined with the
      electrophysiological confirmations of the brain dysfunction following the
      induction of sepsis.

PMID- 20674557
TI  - The origin recognition complex subunit, ORC3, is developmentally regulated and
      supports the expression of biochemical markers of neuronal maturation in cultured
      cerebellar granule cells.
AB  - The origin recognition complex (ORC) regulates DNA replication. However, some
      members of the ORC core, such as ORC3 and ORC5, have been implicated in neuronal
      maturation. In cultured cerebellar granule cells (CGCs), ORC3 mRNA and protein
      levels increased from 6 to 8days in vitro, a time that coincided with the maximal
      development of the dendritic arbor. In contrast, expression of ORC5 remained low
      throughout CGC maturation. Activation of type-4 metabotropic glutamate receptors
      with the selective enhancer, PHCCC, during a critical time-window (from 4 to
      6days in vitro) anticipated the developmental peak of ORC3, increased the
      expression of two proteins associated with neuronal maturation, i.e. the mitogen
      associated protein-2 (MAP-2) and postsynaptic density-95 (PSD-95), as well as
      dendritic length. siRNA-induced ORC3 knockdown reduced MAP-2 and PSD-95
      expression on its own and abrogated the action of PHCCC. We examined whether the
      maturational effects of ORC3 were mediated by changes in the activity of the
      monomeric GTP-binding protein, Rho, which is known to regulate granule cell
      morphology. ORC3 knockdown increased the levels of the GTP-bound active form of
      Rho, whereas exposure to PHCCC reduced Rho activation. The action of PHCCC was
      largely attenuated in cultures deprived of ORC3. Finally, granule cell exposure
      to the Rho-associated kinase inhibitor, Y-27632, abolished the lowering effect of
      ORC3 knockdown on MAP-2 expression, and increased dendritic length. These data
      suggest that ORC3 supports neuronal maturation by inhibiting the Rho signaling
      pathway, and mediates the differentiating activity of mGlu4 receptors in cultured
      cerebellar granule cells.

PMID- 20674558
TI  - 1-(3',4',5'-Trimethoxyphenyl)-3-(3'',4''-dimethoxy-2''-hydroxyphenyl)-propane
      with microtubule-depolymerizing ability induces G2/M phase arrest and apoptosis
      in HepG2 cells.
AB  - 1-(3',4',5'-Trimethoxyphenyl)-3-(3'',4''-dimethoxy-2''-hydroxyphenyl)-propane
      (DP), a novel synthesized 1,3-diarylpropanes compound, showed growth inhibitory
      effect on human hepatoma HepG2 cells in a concentration-dependent manner. The
      growth inhibitory effect of DP on HepG2 cells was associated with microtubule
      depolymerization, G2/M phase arrest and apoptosis induction. The G2/M phase
      arrest induced by DP resulted from its microtubule-depolymerizing ability, and DP
      treated HepG2 cells finally underwent caspase-dependent apoptosis. DP increased
      the levels of death receptor 4 (DR4), death receptor 5 (DR5) and pro-apoptotic
      protein Bax, but decreased the levels of anti-apoptotic protein Bcl-2. Meanwhile,
      the decrease in the mitochondrial membrane potential (MMP) and the release of
      cytochrome c from mitochondria were observed in DP-treated HepG2 cells. DP
      increased the levels of reactive oxygen species (ROS) in HepG2 cells, and
      antioxidant N-acetylcysteine (NAC) completely blocked DP-induced ROS accumulation
      and the disruption of the balance between Bax and Bcl-2 proteins, and effectively
      blocked the decreased MMP and apoptosis, but had no effect on the activation of
      caspase-8 and the up-regulations of DR4 and DR5 induced by DP. These results
      suggest that DP induces G2/M phase arrest through interruption of microtubule
      network followed by the death receptor- and ROS-mediated apoptosis in HepG2
      cells.

PMID- 20674559
TI  - H(2)O(2) preferentially synergizes with nitroprusside to induce apoptosis
      associated with superoxide dismutase dysregulation in human melanoma irrespective
      of p53 status: Antagonism by o-phenanthroline.
AB  - The pro-oxidant hydrogen peroxide (H(2)O(2)) is converted to a reactive oxygen
      species by transition metals like iron. Since mutations in the p53 tumor
      suppressor gene contribute to drug resistance, we used genetically-matched human
      C8161 melanoma harbouring wt or DN-R175H mutant p53, to investigate the influence
      of p53 status on the potentiation of H(2)O(2) toxicity by: (a) intact sodium
      nitroprusside or nitroferricyanide (SNP), (b) its light-exhausted NO-depleted
      form (lex-SNP), (c) potassium ferricyanide, or (d) ferric ammonium sulphate.
      Whereas single treatments with SNP or H(2)O(2) were partly cytotoxic,
      preferentially potentiation of H(2)O(2) toxicity was evidenced with intact or lex
      SNP. No comparable increase of H(2)O(2) toxicity was induced by ferricyanide,
      ferric ammonium sulphate or S-nitroso-N-acetyl penicillamine (SNAP), a known NO
      donor lacking iron. Immune blotting revealed apoptosis-associated PARP cleavage
      induced by [SNP+H(2)O(2)] irrespective of p53 status. This correlated with an
      eightfold induction of [Mn-SOD; SOD2] in wt p53 melanoma cells, and with a super
      induction of the same enzyme reciprocal with loss of [Cu,Zn-SOD; SOD1], in mutant
      p53 cells. All these changes were antagonized by the anti-oxidant N
      acetylcysteine or the iron chelator o-phenanthroline. We hypothesize that
      superoxide dismutase imbalance and iron-dependent redox changes involving OH
      species generated from a Fenton reaction between [SNP+H(2)O(2)], may be important
      in this anti-tumor activity. Although tumor drug resistance is frequently
      associated with DN-p53 mutations, our data shows for the first time the
      preferential ability of SNP to enhance H(2)O(2) toxicity, irrespective of p53
      status.

PMID- 20674560
TI  - Identification of serum proteins that bind with S100A8, S100A9 and S100A8/A9:
      clinical significance of using proteins for monitoring the postoperative
      condition of liver recipients.
AB  - BACKGROUND: Serum proteins that non-specifically bind with human S100A8/A9 (h
      S100A8/A9) have been proposed. Our aim was to isolate and identify these
      proteins, and verify their clinical significance for monitoring the postoperative
      condition of liver recipients, and further to discuss the transportation of human
      fibronectin (h-FN) with h-S100A8/A9 and its functional role in vivo. METHODS: To
      isolate the serum proteins, recombinant human S100A8, S100A9 and S100A8/A9
      affinity columns were used. Proteins were identified by mass spectrometry. Two
      enzyme-linked immunosorbent assays (ELISA) were used to measure h-S100A8/A9 and h
      FN in the sera of liver recipients. Flow cytometry was employed to detect h
      S100A8/A9 and h-FN on immunological cells. Western blotting was used to confirm
      serum constituents using antibodies specific to each constituent. RESULTS: One of
      the proteins was identified with h-FN, and its fluctuation pattern in the serum
      of the recipient was in contrast to that of CRP. Flow cytometry showed a positive
      reaction for h-S100A8/A9 and h-FN on neutrophils and monocytes, indicating that
      both proteins exist on these cells. CONCLUSIONS: The h-FN could be transported
      with S100A8/A9 in blood and/or on immunological cells, and effectively prevent
      further attack by various internal oxidants or repair damaged liver tissue in
      vivo.

PMID- 20674561
TI  - A promoter polymorphism -2122C>T of CHI3L1 is associated with serum low density
      lipoprotein cholesterol level in Korean subjects.
AB  - OBJECTIVES: This study assessed the effects of 10 tagging single nucleotide
      polymorphisms (SNPs) of the CHI3L1 gene on serum LDL cholesterol levels in 290
      Korean subjects. DESIGN AND METHODS: Genotyping analyses of SNPs were conducted
      by TaqMan(r) method. The effects of the promoter SNP on mRNA expression and
      nuclear factor binding were measured by real-time PCR and electrophoretic
      mobility shift assay, respectively. RESULTS: Among 10 tagging SNPs, -2122C>T SNP
      (rs946261) in the promoter region was significantly associated with serum LDL
      cholesterol level (P=0.005). The T allele of -2122C>T was associated with
      significantly increased mRNA expressions in peripheral blood cells of the
      subjects, and also increased a nuclear factor binding measured by an
      electrophoretic mobility shift assay. CONCLUSIONS: -2122C>T of CHI3L1, a promoter
      SNP which affects the mRNA expression and nuclear factor binding, is
      significantly associated with serum LDL cholesterol levels in Korean subjects.

PMID- 20674562
TI  - Hepatoma-derived growth factor promotes the resistance to anti-tumor effects of
      nordihydroguaiaretic acid in colorectal cancer cells.
AB  - Hepatoma-derived growth factor (HDGF) is correlated with aggressive tumor
      behaviors such as invasion and angiogenesis. Nevertheless, the potential
      involvement of HDGF in cell resistance to natural plant phenols-based
      chemotherapy is still unclear. This study demonstrated that over-expression of
      HDGF could confer the resistance of human colorectal cancer (CRC) cells to
      nordihydroguaiaretic acid (NDGA) toxicity. Enforced expression of HDGF could
      inhibit NDGA-induced apoptosis through the mitochondrial pathway in CRC cells,
      and attenuate the inhibitory effect of NDGA on tumor growth. Therefore, our
      results suggest that HDGF represents a potential molecule associated with
      chemotherapy resistance, which may have major implications in improving
      chemotherapy of colorectal cancer.

PMID- 20674563
TI  - Sulfur dioxide upregulates the aortic nitric oxide pathway in rats.
AB  - Sulfur dioxide (SO(2)) is a common gaseous pollutant. It is also, however,
      endogenously generated from sulfur-containing amino acids. Recent studies have
      demonstrated that rat blood pressure can be lowered by SO(2)-exposure in vivo and
      that vasodilation caused by SO(2) at low concentrations (<450 microM) is
      endothelium-dependent in rat aorta. However, effects of SO(2) on nitric oxide
      synthase (NOS) and nitric oxide (NO) production have not been previously studied
      in rat aorta. The objective of the present study is to assess the effects of
      acute (10 min) and prolonged (2h) stimulation with different concentrations of
      SO(2) on NO/cGMP pathway in isolated rat aorta. The results show that: (1) the
      acute and prolonged pretreatments with SO(2) produced an inhibition of
      vasoconstrictions induced by norepinephrine. (2) SO(2) potentiated activity of
      endothelial nitric oxide synthase (eNOS), but not of induced NOS (iNOS). (3)
      SO(2) could increase expression of eNOS gene on the transcription and translation
      levels in rat aorta. (4) SO(2) enhanced NO formation in aortic tissue. (5) The
      level of cGMP in rat aorta was increased by SO(2) and no change of cAMP. These
      findings led to the conclusion: there were acute and prolonged effects of SO(2)
      on the NO/cGMP signalling pathway; and SO(2) could upregulate the eNOS-NO-cGMP
      pathway and at least partly by which the SO(2) might cause vasodilation and
      inhibition to vasoconstriction.

PMID- 20674564
TI  - In vitro binding characteristics of [3H]AZ11637326, a novel alpha7-selective
      neuronal nicotinic receptor agonist radioligand.
AB  - AZ11637326 (5'-(2-fluoro[3,4,5(-3)H3]phenyl)-spiro[1-azabicyclo [2.2.2]octane
      3,2'(3'H)-furo[2,3-b]pyridine) is a potent partial agonist at the human alpha7
      neuronal nicotinic receptor with sub-nanomolar affinity for the human and rat
      alpha7 [(125)I]alpha-bungarotoxin binding sites. In a search for novel agonist
      radioligands and imaging ligands for the alpha7 nicotinic receptor,
      [(3)H]AZ11637326 was synthesized and its in vitro membrane binding properties
      were characterized. [(3)H]AZ11637326 bound to halpha7-HEK membranes with high
      specificity (>95%), high affinity (230 pM) and a B(max) of 460 fmol/mg. The rank
      order of affinity of nicotinic standards determined with [(3)H]AZ11637326
      strongly correlated with those determined using the classical alpha7 antagonist
      [(125)I]alpha-bungarotoxin, indicating that [(3)H]AZ11637326 bound to halpha7-HEK
      membranes with an alpha7 nicotinic-like pharmacology. The K(i) values for the
      standards were on average 2.3-fold lower affinity than determined using the
      prototypical alpha7 nicotinic antagonist [(125)I]alpha-bungarotoxin. Because
      [(3)H]AZ11637326 specific binding is rapid and reversible, the K(i) values
      determined using this ligand are more accurate estimates of affinity than those
      determined using the kinetically sluggish [(125)I]alpha-bungarotoxin.
      [(3)H]AZ11637326 also bound to a high affinity (510 pM), nicotine-sensitive site
      on rat hippocampal membranes with an average B(max) of 55 fmol/mg. With rat
      hippocampal membranes, the nicotine-sensitive fraction of total binding was sub
      optimal for a radioligand (~50%), yet the potencies and rank order of the K(i)
      values for standards were consistent with an alpha7 nicotinic pharmacology.
      Overall, these studies indicate that [(3)H]AZ11637326 is a useful new in vitro
      probe of the alpha7 nicotinic receptor agonist site and support its potential
      utility for in vivo receptor occupancy studies.

PMID- 20674565
TI  - Comparison of the efficacy of tacrolimus and cyclosporine A in a murine model of
      dinitrofluorobenzene-induced atopic dermatitis.
AB  - Tacrolimus (FK506) and cyclosporine A (Cys A) are immunosuppressive drugs used in
      the treatment of inflammatory diseases and for preventing rejection of allogeneic
      transplants. Tacrolimus forms a complex with FK506 binding protein (FKBP), and
      Cys A forms a complex with cyclophilin. These tacrolimus-FKBP and Cys A
      cyclophilin complexes interact with calcineurin (CaN), thereby suppressing
      activation of T cells. In contrast, steroidal anti-inflammatory drugs suppress
      the immune system mainly via inhibition of nuclear factor kappa-light-chain
      enhancer of activated B cells (NF-kappaB) and the activating protein-1 (AP-1)
      pathway. Previously, we reported that tacrolimus, but not dexamethasone, reduced
      scratching behavior in a murine model of atopic dermatitis. To elucidate the
      mechanism involved in the inhibition of scratching behavior, we used a mouse
      model of allergic dermatitis to compare the characteristics of tacrolimus and Cys
      A treatment. We found that Cys A suppressed scratching behavior induced by
      application of 2,4-dinitrofluorobenzene, as did tacrolimus. In addition, both
      drugs attenuated increases in vascular permeability and scratching behavior
      induced by passive cutaneous anaphylaxis. These results indicate that inhibition
      of the CaN pathway plays an important role in tacrolimus- and Cys A-induced
      inhibition of scratching behavior in mice. Furthermore, we observed that CaN
      inhibitors suppressed mast cell-dependent allergic reaction.

PMID- 20674566
TI  - Effects of the NOP receptor agonist Ro65-6570 on the acquisition of opiate- and
      psychostimulant-induced conditioned place preference in rats.
AB  - Activation of the Nociceptin/Orphanin FQ (NOP) receptor may have anti-abuse
      effects. The present study examined the consequence of NOP receptor activation on
      the rewarding effect of opiates and psychostimulants in the conditioned place
      preference task in rats. First, the motivational effect of the NOP receptor
      agonists Ro64-6198 (0.316-3.16 mg/kg i.p.) and Ro65-6570 (1-10mg/kg i.p.) when
      administered alone, was assessed. Ro65-6570 was selected for further drug
      combination studies since, unlike Ro64-6198, it was devoid of an intrinsic
      motivational effect. Next, the minimal effective dose to induce reward for the
      opiates heroin (0.1-3.16 mg/kg i.p.), morphine (1-10mg/kg i.p.), hydrocodone
      (0.316-10mg/kg i.p.), tilidine (1-31.6 mg/kg i.p.), hydromorphone (0.1-10mg/kg
      i.p.), and oxycodone (0.0316-10mg/kg i.p.), as well as for the psychostimulants
      cocaine (3.16-31.6 mg/kg i.p.) and dexamphetamine (0.316-3.16 mg/kg i.p.) in
      combination with Ro 65-6570 (0 or 3.16 mg/kg i.p.) was determined. All drugs
      produced conditioned place preference, and for opiates and cocaine, but not for
      dexamphetamine, the minimal effective dose was higher when combined with Ro65
      6570 (3.16 mg/kg i.p.). Attenuation of the rewarding effect of tilidine (3.16
      mg/kg i.p.) and oxycodone (1mg/kg i.p.) by Ro65-6570 (3.16 mg/kg i.p.) could be
      reversed by pre-treatment with the NOP receptor antagonist J-113397 (4.64 mg/kg
      i.p.), suggesting that the attenuating effect of Ro65-6570 on opiates is due to
      activation of the NOP receptor. Taken together, the present study suggests that
      activation of NOP receptors effectively attenuates the rewarding effect of
      opiates, but may be less effective in reducing psychostimulant-induced reward.

PMID- 20674567
TI  - Gatifloxacin-induced histamine release and hyperglycemia in rats.
AB  - Gatifloxacin, a fluoroquinolone antimicrobial agent, has been reported to cause
      both hypoglycemia and hyperglycemia in diabetic and non-diabetic patients. The
      purpose of the present study was to investigate the mechanism of gatifloxacin
      induced hyperglycemia in normal and diabetic rats. Rats received a single
      intravenous injection of gatifloxacin and samples of their arterial blood were
      collected periodically. Diabetic rats were produced by the injection of
      streptozotocin and nicotinamide. In normal rats, the concentration of serum
      glucose decreased after the injection of gatifloxacin at 50mg/kg, while it
      increased with gatifloxacin at 100mg/kg. The concentrations of serum epinephrine
      and histamine increased after the injection of gatifloxacin at 100mg/kg. The
      increases in serum glucose and epinephrine concentrations were reduced by
      pretreatment with diphenhydramine at 1mg/kg. In diabetic rats, the concentration
      of serum glucose actually increased after the injection of gatifloxacin at
      50mg/kg, concomitant with increases in the serum epinephrine and histamine
      concentrations. The concentration of serum immunoreactive insulin slightly
      increased after the injection of gatifloxacin at 50mg/kg. In addition, repeated
      oral administration of gatifloxacin to rats at 300 mg/kg twice a day for 7 days
      did not change glucose tolerance. In conclusion, gatifloxacin-induced release of
      histamine can contribute to an increase in the serum epinephrine concentration
      and hyperglycemia in normal rats. In diabetic rats, lower doses of gatifloxacin
      can induce hyperglycemia owing to the low level of insulin secretion that they
      exhibit compared with normal animals.

PMID- 20674568
TI  - Generation of trans-mitochondrial mito-mice by the introduction of a pathogenic
      G13997A mtDNA from highly metastatic lung carcinoma cells.
AB  - To investigate the effects of respiration defects on the disease phenotypes, we
      generated trans-mitochondrial mice (mito-mice) by introducing a mutated G13997A
      mtDNA, which specifically induces respiratory complex I defects and metastatic
      potentials in mouse tumor cells. First, we obtained ES cells and chimeric mice
      containing the G13997A mtDNA, and then we generated mito-mice carrying the
      G13997A mtDNA via its female germ line transmission. The three-month-old mito
      mice showed complex I defects and lactate overproduction, but showed no other
      phenotypes related to mitochondrial diseases or tumor formation, suggesting that
      aging or additional nuclear abnormalities are required for expression of other
      phenotypes.

PMID- 20674569
TI  - Nucleosome deposition and DNA methylation may participate in the recognition of
      premature termination codon in nonsense-mediated mRNA decay.
AB  - In non-mammalian eukaryotes, an abnormally long 3' untranslated region (UTR) is
      generally thought to be the definitive signal in the recognition of a premature
      termination codon (PTC) in nonsense-mediated mRNA decay (NMD). However, because
      the lengths of 3' UTRs in normal mRNAs are widely distributed, "abnormally long"
      is hard to define. Distinct peaks of nucleosome deposition and DNA methylation
      have recently been found at coding region boundaries. We propose that nucleosomes
      and DNA methylation just upstream of a normal stop codon are ideal indicators for
      the position of a normal stop codon and may thus serve as signals in PTC
      recognition.

PMID- 20674571
TI  - Osmoregulated trehalose-derived oligosaccharides in Sinorhizobium meliloti.
AB  - Sinorhizobium meliloti is a soil bacterium accumulating glutamate, N
      acetylglutaminyl glutamine amide and trehalose in hyperosmolarity. Besides these
      compatible solutes, we highlighted several compounds in S. meliloti Rm1021 wild
      type strain. The purification and the structural characterization based on liquid
      chromatography evaporative light scattering detector, electrospray ionization
      high resolution mass spectrometry and nuclear magnetic resonance techniques
      showed they were four linear oligosaccharides composed of 3, 4, 5 and 6 glucose
      units all linked by alpha-(1-->2) linkages except a terminal alpha-(1<-->1)
      linkage. These oligosaccharides were cytoplasmic and were observed in several
      wild-type strains suggesting they were common features in S. meliloti strains
      grown in hyperosmolarity.

PMID- 20674572
TI  - Knock-out of metacaspase and/or cytochrome c results in the activation of a ROS
      independent acetic acid-induced programmed cell death pathway in yeast.
AB  - To gain further insight into yeast acetic acid-induced programmed cell death (AA
      PCD) we analyzed the effects of the antioxidant N-acetyl-L-cysteine (NAC) on cell
      viability, hydrogen peroxide (H(2)O(2)) production, DNA fragmentation, cytochrome
      c (cyt c) release and caspase-like activation in wild type (wt) and metacaspase
      and/or cyt c-lacking cells. We found that NAC prevents AA-PCD in wt cells, by
      scavenging H(2)O(2) and by inhibiting both cyt c release and caspase-like
      activation. This shows the occurrence of a reactive oxygen species (ROS)
      dependent AA-PCD. Contrarily no NAC dependent change in AA-PCD of mutant cells
      was detectable, showing that a ROS-independent AA-PCD can also occur.

PMID- 20674573
TI  - The role of telomeres and telomerase in stem cell aging.
AB  - Stem cells regenerate our bodies. In a similar manner to match ignition, stem
      cell "ignition" has to be precisely tuned to avoid uncontrolled proliferation as
      may occur in tumors or, inversely, the lack of proliferation as happens in
      degenerative disorders. During the last years it has become evident that
      telomeres and telomerase are main components of the stem cell "ignition"
      mechanism, providing a way to restrain cancer and delay aging.

PMID- 20674574
TI  - Crystal structure of Bifidobacterium Longum phosphoketolase; key enzyme for
      glucose metabolism in Bifidobacterium.
AB  - The crystal structure of Bifidobacterium longum phosphoketolase, a thiamine
      diphosphate (TPP) dependent enzyme, has been determined at 2.2A resolution. The
      enzyme is a dimer with the active sites located at the interface between the two
      identical subunits with molecular mass of 92.5 kDa. The bound TPP is almost
      completely shielded from solvent except for the catalytically important C2-carbon
      of the thiazolium ring, which can be accessed by a substrate sugar through a
      narrow funnel-shaped channel. In silico docking studies of B. longum
      phosphoketolase with its substrate enable us to propose a model for substrate
      binding.

PMID- 20674575
TI  - The novel finding of four distinct prepro-IGF-I E domains in a perciform fish,
      Sciaenops ocellatus, during ontogeny.
AB  - In fishes, insulin-like growth factor-I (IGF-I) stimulates growth and
      differentiation but also plays a role in a number of other processes including
      osmoregulation, metabolism, immune response and reproduction. This study presents
      the cDNA encoding multiple prepro-IGF-I transcripts obtained from red drum,
      Sciaenopsocellatus, and examines differential expression in select adult tissues
      and during ontogeny. Four distinct transcripts were sequenced which were
      identical in the coding region for the signal (132 bp) and mature (204 bp)
      peptides but differed in the coding region of the E peptide by the exclusion of
      117 (Ea-1), 81 (Ea-2) or 36 (Ea-3) bp compared to the 222 bp present in Ea-4.
      Analysis of the pertinent portion of the genomic sequence of this gene suggests
      that the transcripts are a result of alternative splicing. This is the first
      report of the expression of all four known prepro-IGF-I transcripts in a teleost
      other than a salmonid. The deduced amino acid sequences exhibited 70-95% identity
      with teleosts and somewhat lower identity to other vertebrates (60-75%). Three of
      the 4 transcripts (Ea-2, Ea-3, Ea-4) were expressed in the liver, ovary, spleen,
      gall bladder, brain, red muscle, pancreas and spinal cord of adults. Only the Ea
      4 transcript was expressed in adult stomach tissue while no signal was detected
      in pituitary, retina, intestine, adipose or white muscle. In contrast, all 4
      transcripts were expressed throughout ontogeny. The apparent expression of the Ea
      1 transcript only during the larval stage may indicate a developmental role for
      this E peptide in red drum.

PMID- 20674576
TI  - Immunostaining of Atlantic salmon (Salmo salar L.) leucocytes.
AB  - Different salmon leucocyte subpopulations were identified by immunostaining using
      rabbit antiserum raised against the salmonid cell line TO derived from head
      kidney leucocytes in combination with other available immunoglobulins. The rabbit
      anti-TO cell line serum immunostained all isolated leucocytes from head kidney,
      peripheral blood and spleen, as shown by analyses of these leucocytes by flow
      cytometry and by fluorescence microscopy. In cytospin preparations, the staining
      of salmon leucocytes using rabbit anti-TO serum as the primary antibody revealed
      greater morphological details compared to conventional staining procedures,
      especially among isolated spleen leucocytes where cells with a morphology usually
      limited to dendritic cells were seen. Other cells of various shapes and
      protrusions were also stained although the anti-TO serum did not stain
      protrusions on all cell types. Among the immunoglobulin positive cells, the thin
      protrusions were only seen when immunostained using anti-IgM antibody. The same
      was observed for neutrophils stained using the monoclonal E3D9 antibody. The
      double staining of cells using rabbit anti-TO serum and monoclonal antibodies
      specific for IgM positive cells or neutrophils clearly show how the morphology of
      these cells can be compared with the rest of the leucocyte population. The
      staining of salmon leucocytes by antiserum to a salmon leucocyte cell line TO
      provides a tool for staining the total population of salmon immune cells, and can
      be used in immunofluorescence or confocal microscopy in combinations with
      labelling of cellular components or pathogens. The detailed morphological
      characteristics, such as cell protrusions, visualized by the presented staining
      have not been observed on fish leucocytes by conventional cell staining
      procedures.

PMID- 20674577
TI  - Identification of a novel monoclonal antibody recognizing CD133.
AB  - Human CD133 (prominin-1), a cell surface glycoprotein, is used as a marker of
      hematopoietic and neural stem cells. Antibodies that recognize a glycosylation
      dependent CD133 epitope have been extensively used for enrichment of tumor
      initiating cells in a variety of cancers. These currently available antibodies
      are restricted for use in only a subset of biological assays. We have generated a
      novel anti-human CD133 monoclonal antibody, using a recombinant protein
      consisting of highly immunogenic amino acid residues selected from the native
      CD133 protein as an immunogen. The antibody (identified as clone 7) specifically
      recognizes the CD133 protein in a variety of immunological applications including
      Western blot, immunofluorescence, flow cytometry and immunohistochemistry.
      Further, clone 7 specifically recognizes an unmodified CD133 extracellular
      domain, and not its glycosylated epitope. In conclusion, the specificity and
      usefulness in a wide range of applications suggest that clone 7 could be a
      valuable tool to identify CD133 positive cells as well as to target them for
      therapy.

PMID- 20674578
TI  - Insect-toxic secreted proteins and virulence of the entomopathogenic fungus
      Beauveria bassiana.
AB  - Fungal virulence has been mostly associated with cuticle-degrading enzymes that
      can be regulated depending on nutrient conditions. However, few studies have
      related fungal virulence to insect-toxic secreted proteins. Here, we describe how
      the presence of secreted toxic proteins may be linked to conidial virulence,
      which can be affected by nutrient factors. In this study we evaluated: (1) the
      virulence of the conidia of four Beauveria bassiana strains (EABb 01/103-Su, EABb
      01/12-Su, EABb 01/88-Su and EABb 01/110-Su) grown on three different media (malt
      extract agar (MA), Rice (Rice), Sabouraud dextrose agar (SDA) and harvested from
      the cadavers of fungal-infected Galleria mellonella larvae (CAD) and (2) the
      toxicity of the crude soluble protein extracts (CSPEs) obtained from Adamek's
      liquid medium inoculated with these conidia. Conidial suspensions were obtained
      from the four media, assessed on G. mellonella larvae and used to produce CSPEs
      that were injected into healthy G. mellonella larvae. The larvae were also
      injected with conidia obtained from MA and CAD cultures to expose them to in vivo
      secreted proteins. For all isolates, the CAD conidia were by far the most
      virulent, followed by conidia grown on SDA, Rice and MA. The injected CSPEs
      showed the same toxicity trends as the conidial suspensions. In addition, the
      outcomes of injection of the in vivo-secreted proteins showed that the toxic
      proteins secreted in vitro by the EABb 01/110-Su strain are not produced in vivo.
      However, the other strains produced toxic proteins both in vivo and in vitro,
      suggesting that these toxic proteins may be virulence factors involved in
      invertebrate pathogenesis.

PMID- 20674579
TI  - Cardiovascular determinants and prognostic significance of CC Chemokine Ligand-18
      (CCL18/PARC) in patients with stable coronary artery disease.
AB  - Chemokines are important mediators of angiogenesis, hematopoiesis and leucocyte
      trafficking. CC Chemokine Ligand-18 (CCL18)/ pulmonary and activation-regulated
      chemokine (PARC) is a circulating chemokine that plays a role in injury healing,
      physiological homing of mononuclear blood cells and inflammatory responses.
      CCL18/PARC is also expressed in atherosclerotic plaques. We prospectively
      evaluated CCL18/PARC levels and their cardiovascular and biological determinants
      in a large cohort of 285 patients with stable coronary heart disease who were
      subsequently followed for 3 years for hard cardiac events. It was found that
      CCL18/PARC levels were associated with decreased cardiac function, decreased
      exercise capacity and increased inflammatory parameters including interleukin-6
      (IL-6) and hs-CRP. More importantly high CCL18/PARC levels were an independent
      predictor of future cardiovascular events. Therefore, CCL18/PARC is a potential
      diagnostic and prognostic parameter in patients with stable coronary artery
      disease.

PMID- 20674580
TI  - Bordered tug-of-war models are neither general nor predictive of reproductive
      skew.
AB  - Models of reproductive skew assume reproductive shares are either conceded,
      competed over, or both. Previous mathematical evaluations found that simultaneous
      concessions and contests are evolutionarily unstable. Recently, Shen and Reeve
      (2010) challenged these conclusions and developed a series of sub-models they
      argued to be a unified approach to reproductive skew: the general bordered tug-of
      war (BTOW). However, BTOW fails as a general model for two reasons: (1) the BTOW
      strategy cannot invade populations where individuals either only compete for or
      only concede reproductive shares and (2) contrary to Shen and Reeve's assertion,
      BTOW populations are easily invaded by strategies with fewer or no concessions,
      but competing at lower levels. The failure of BTOW as a general model has major
      implications for interpreting experiments on reproductive skew. A large number of
      studies have measured the effects of genetic relatedness and competitive ability
      on reproductive skew, with a great majority finding no significant correlation
      between variation in within-group relatedness or competitive ability and across
      group differences in skew. No model of reproductive skew except one variant of
      the BTOW predicts such results. With the rejection of BTOW as a valid general
      model, it is clear that these results are contradictory to reproductive skew
      theory rather than supportive of it.

PMID- 20674581
TI  - Cholesterol myristate suppresses the apoptosis of mesenchymal stem cells via
      upregulation of inhibitor of differentiation.
AB  - To identify small molecules that suppress the apoptosis of mesenchymal stem cells
      (MSCs) is promising for stem cell therapy. We recently showed that bone
      morphogenetic protein 4 (BMP4) signalling involves the effect of cholesterol
      myristate on the proliferation of MSCs. The present study evaluated the effects
      of cholesterol myristate on the apoptosis of MSCs and the inhibitor of
      differentiation (Id1), target gene of BMP4 signalling. MSCs transfected by the
      Id1 promoter reporter construct, cholesterol myristate increases the activity of
      Id1 promoter. However, structurally related steroids such as cholesterol, beta
      sitosterol and cholesten-3-one, lack of the myristate, did not affect the
      activity of Id1 promoter, suggesting that myristate is essential for this effect.
      This effect depends on BMP signalling. Apoptosis analysis indicated that
      cholesterol myristate inhibited the apoptosis of MSCs induced by serum-free.
      Cholesterol myristate increases the expression of Id1 and its target gene bcl-x/l
      in MSCs treated with serum-free. Moreover, noggin, a BMP antagonist, reduced the
      anti-apoptotic effects of cholesterol myristate. Thus, this study aims to provide
      evidence that cholesterol myristate suppresses the apoptosis of MSCs via up
      regulation of Id1. These findings can be applied for improving MSCs survival in
      stem-cell transplantation, bone-marrow transplantation, treatment of bone
      diseases such as osteoporosis and chemotherapy.

PMID- 20674582
TI  - Species coexistence under resource competition with intraspecific and
      interspecific direct competition in a chemostat.
AB  - Competition theory has developed separately for direct competition and for
      exploitative competition. However, the combined effects of the two types of
      competition on species coexistence remain unclear. To examine how intraspecific
      and interspecific direct competition contributes to the coexistence of species
      competing for a single resource, we constructed a chemostat-type resource
      competition model. With general functions for intraspecific and interspecific
      direct competition, we derived necessary and sufficient conditions (except for a
      critical case that rarely occurs in a biological sense) that determine the number
      of stably coexisting species. From these conditions, we found that the number of
      coexisting species is determined just by the invasibility of each species into
      subcommunities with a smaller number of species. In addition, using a combination
      of rigorous mathematical theory and a simple graphical method, we can demonstrate
      how the stronger intraspecific direct competition facilitates species invasion,
      leading to a larger number of coexisting species.

PMID- 20674583
TI  - Characterization of 27-hydroxy-13-desmethyl spirolide C and 27-oxo-13,19
      didesmethyl spirolide C. Further insights into the complex Adriatic Alexandrium
      ostenfeldii toxin profile.
AB  - Alexandrium ostenfeldii is a widespread toxic dinoflagellate that has recently
      bloomed across the Adriatic Sea, seriously threatening both shellfish consumers
      and aquacultures. In 2007 we reported on preliminary studies carried out on field
      samples and cultures of A. ostenfeldii. At the time, along with three major
      spirolides - among which 27-hydroxy-13,19-didesmethyl spirolide C (3) proved to
      be a novel compound - a number of new minor spirolides were detected.
      Unfortunately, for all of them only Mass Spectrometry-based structural hypotheses
      could be ventured due to their very small amount. In the present paper we report
      on isolation and High Resolution Mass Spectrometry- and NMR-based structural
      elucidation of two of those minor spirolides detected in our previous study.

PMID- 20674584
TI  - Effects of A2 type botulinum toxin on spontaneous miniature and evoked
      transmitter release from the rat spinal excitatory and inhibitory synapses.
AB  - We observed effects of newly developed A2 type botulinum toxin (A2NTX) on
      spontaneous miniature and evoked transmitter release from inhibitory (glycinergic
      or GABAergic), or excitatory (glutamatergic) nerve terminals in rat spinal cord,
      by use of 'synaptic bouton' preparations, under voltage-clamp condition. A2NTX
      (0.1-1 pM) initially augmented and then decreased amplitude and frequency of
      spontaneous miniature release of glycine or GABA (mIPSCs) concentration
      dependently. At an increased concentration (1-10 pM), A2NTX suppressed the
      amplitude of glutamatergic mEPSCs. The rank order of the inhibitory effects was
      glycinergic > GABAergic >> glutamatergic synapses. Focal electrical stimulation
      of 'synaptic boutons' elicited eIPSC or eEPSC with larger amplitude and low
      failure rate (Rf). A2NTX (0.01-1 pM) initially enhanced the amplitude or
      decreased the failure rate of eIPSC or eEPSC, and then almost completely
      abolished the generation of eIPSC or eEPSC. The action of A2NTX on the evoked
      transmitter release was partially reversible. The rank order of the inhibitory
      effects on the amplitude or Rf were glycinergic eIPSC >= GABAergic eIPSC >
      glutamatergic eEPSCs. Excess extracellular K(+) or Ca(2+) (excess [K(+)](o) or
      [Ca(2+)](o)), and 4-AP restored spontaneous miniature glycinergic, GABAergic or
      glutamatergic postsynaptic currents suppressed by A2NTX. We conclude that A2NTX
      inhibits spontaneous miniature release at 0.1-10 pM and evoked release at 0.01-1
      pM in rat spinal cord, and the inhibition was much efficient in the evoked rather
      than the spontaneous miniature release. Excess [K(+)](o), 4-AP and excess
      [Ca(2+)](o), which can raise the intracellular Ca(2+) concentration via the
      activation of voltage-dependent Ca(2+) channels, rescue the transmission
      suppressed by A2NTX poisoning, suggesting the transmitter release machinery
      became less sensitive to intracellular Ca(2+) in A2NTX poisoned 'synaptic
      boutons'.

PMID- 20674585
TI  - Endoplasmic reticulum stress in murine liver and kidney exposed to microcystin
      LR.
AB  - To investigate the effect of microcystin-LR (MC-LR) on apoptosis based on the
      endoplasmic reticulum stress (ERS) pathway in mouse liver and kidney, male ICR
      mice were intraperitoneally injected with 20 MUg kg(-1) body weight MC-LR for 21
      days, and mRNA and protein levels of ERS special molecules in liver and kidney
      were analyzed using quantitative real-time PCR and western blotting. MC-LR
      significantly improved mRNA and protein expression of C/EBP homologous protein
      (CHOP) and cleaved caspase-12 in liver, whereas it inhibited expression of CHOP
      and caspase-12 in kidney. MC-LR also induced significant down-regulation of B
      cell lymphoma/leukemia-2 (Bcl-2) mRNA expression in liver and weak up-regulation
      in kidney. These results indicated the involvement of the ERS pathway in MC-LR
      induced apoptosis of hepatic cells but not in renal cells of mice. The weight
      changes and histological damage of liver and kidney were in accordance with the
      appearance of ERS. Our results indicate that ERS plays an important role in
      hepatic cell apoptosis induced by MC-LR, and is considered as a new pathway of
      liver toxicity. Its relative special genes might be considered as potentially new
      biomarkers used for risk assessment of MC-LR in the environment.

PMID- 20674586
TI  - Recombinant expression in human cells of active integrin alpha 1 beta 1-blocking
      RTS-disintegrin jerdostatin.
AB  - Jerdostatin, an RTS short disintegrin cloned from Protobothrops jerdonii and
      recombinantly produced in Escherichia coli, is a potent and specific antagonist
      of the alpha(1)beta(1) integrin. Jerdostatin selectively blocked the adhesion of
      alpha(1)beta(1)-K562 cell to collagens I and IV in vitro and angiogenesis in
      vivo. Here we report the recombinant production of jerdostatin in a mammalian
      cell system, a prerequisite for developing a conditional transgenic mouse to
      investigate the effect of systemic expression of jerdostatin on tumor
      development. For proper export of jerdostatin, a secretion leader sequence was
      engineered at the protein's N-terminus. A FLAG epitope was also included at the N
      terminus of the mature disintegrin to facilitate its isolation and
      characterization of recombinant jerdostatin (rJerd). This pRc-CMV/FLAG-rJerd
      construct was transiently expressed in HEK-293 cells and was efficiently secreted
      into the culture medium. rJerd bound to recombinant soluble alpha(1)beta(1)
      integrin in a saturable and cation-independent manner. Soluble rJerd also
      inhibited the binding of alpha(1)beta(1) integrin to the CB3 fragment of collagen
      IV in a dose-dependent manner (IC(50) 570 nM). Mammalian cell-expressed
      jerdostatin disrupted the adhesion of RuGli cells to collagen IV. Our results
      highlight pRc-CMV/FLAG-rJerd as a suitable construct for expressing soluble
      active alpha(1)beta(1)-blocking jerdostatin in a mammalian cell system.

PMID- 20674587
TI  - Immunochemical and biological characterization of monoclonal antibodies against
      BaP1, a metalloproteinase from Bothrops asper snake venom.
AB  - BaP1 is a P-I class of Snake Venom Metalloproteinase (SVMP) relevant in the local
      tissue damage associated with envenomations by Bothrops asper, a medically
      important species in Central America and parts of South America. Six monoclonal
      antibodies (MoAb) against BaP1 (MABaP1) were produced and characterized regarding
      their isotype, dissociation constant (K(d)), specificity and ability to
      neutralize BaP1-induced hemorrhagic and proteolytic activity. Two MABaP1 are IgM,
      three are IgG1 and one is IgG2b. The K(d)s of IgG MoAbs were in the nM range. All
      IgG MoAbs recognized conformational epitopes of BaP1 and B. asper venom
      components but failed to recognize venoms from 27 species of Viperidae,
      Colubridae and Elapidae families. Clone 7 cross-reacted with three P-I SVMPs
      tested (moojeni protease, insularinase and neuwiedase). BaP1-induced hemorrhage
      was totally neutralized by clones 3, 6 and 8 but not by clone 7. Inhibition of
      BaP1 enzymatic activity on a synthetic substrate by MABaP1 was totally achieved
      by clones 3 and 6, and partially by clone 8, but not by clone 7. In conclusion,
      these neutralizing MoAbs against BaP1 may become important tools to understand
      structure-function relationships of BaP1 and the role of P-I class SVMP in
      snakebite envenomation.

PMID- 20674588
TI  - Electromagnetic cellular interactions.
AB  - Chemical and electrical interaction within and between cells is well established.
      Just the opposite is true about cellular interactions via other physical fields.
      The most probable candidate for an other form of cellular interaction is the
      electromagnetic field. We review theories and experiments on how cells can
      generate and detect electromagnetic fields generally, and if the cell-generated
      electromagnetic field can mediate cellular interactions. We do not limit here
      ourselves to specialized electro-excitable cells. Rather we describe physical
      processes that are of a more general nature and probably present in almost every
      type of living cell. The spectral range included is broad; from kHz to the
      visible part of the electromagnetic spectrum. We show that there is a rather
      large number of theories on how cells can generate and detect electromagnetic
      fields and discuss experimental evidence on electromagnetic cellular interactions
      in the modern scientific literature. Although small, it is continuously
      accumulating.

PMID- 20674589
TI  - Letter from the editors: clinical trials in nuclear medicine.

PMID- 20674590
TI  - Introduction to clinical decision making.
AB  - In the last few years there has been a remarkable increase in the amount of
      clinical data in the average hospital chart, and more and more problem-solving
      algorithms have been developed. We need better "thinking tools" to help us handle
      the flow of information. The term "clinical decision making" is used to describe
      a systematic way to handle data and algorithms to decide on a best course of
      action. This introductory article discusses some of the problems in establishing
      a decision criterion, both for a population and for an individual patient.
      Comparing the probabilities and utilities of various diagnostic outcomes (true
      positive, false positive, etc.) leads to a diagnostic strategy. The article also
      discusses conditional probability. Bayes' theorem, and likelihood ratios.

PMID- 20674591
TI  - The Clinical Trials Network of the Society of Nuclear Medicine.
AB  - The Clinical Trials Network of the Society of Nuclear Medicine was formed to
      provide quality assurance of both imaging and radiopharmaceutical manufacturing
      in clinical trials. The intention is to register and qualify a large number
      (>200) of sites, both in the United States and internationally, to be able to do
      the positron emission tomography imaging part of clinical trials. Initially, the
      types of trials to be supported include evaluation of novel radiopharmaceuticals
      and trials that use approved or experimental radiopharmaceuticals for early
      assessment of tumor response to novel chemotherapy agents. The Clinical Trials
      Network is organized into 7 committees that provide overall oversight and
      strategic guidance, database management, site qualification and monitoring,
      scanner validation, clinical site orientation, technologist education, trial
      design, and a manufacturer's registry. At the end of the first year, more than
      200 potential clinical trial sites and more than 125 manufacturing sites have
      expressed interest in participating. The qualification process is well underway.
      Funding is being provided by 3 large pharmaceutical companies. An investigational
      new drug application has been obtained for F-18 fluorothymidine that is held by
      Society of Nuclear Medicine to allow simplification of data management during
      multisite trials with F-18 fluorothymidine. A second investigational new drug
      application is in preparation for F-18 fluoromisonidazole. A supply of oncology
      chest phantoms has been manufactured and have been shipped to numerous sites for
      scanner validation. Educational materials are being developed for the physicians,
      technologists, and research coordinators at the sites. This is an important
      initiative that is likely to help significantly expand the role of molecular
      imaging and will help bring the right treatment to the right patient at the right
      time.

PMID- 20674592
TI  - Design of clinical trials.
AB  - Clinical trial design for nuclear medicine diagnostic imaging
      radiopharmaceuticals must include a design for preclinical safety studies. These
      studies should establish that the investigational product (IP) does not have a
      toxic effect. As a further requirement, radiopharmaceutical clinical trials
      include a human study (phase 1) that provides biodistribution, pharmacokinetics,
      and radiation dosimetry information. These studies demonstrate to the Food and
      Drug Administration that the IP either meets or exceeds the toxicology and
      radiation exposure safety limits. Satisfying this requirement can result in the
      Food and Drug Administration approving the performance of late-phase (phase 2/3)
      clinical trials that are designed to validate the clinical efficacy of the
      diagnostic imaging agent in patients who have a confirmed diagnosis for the
      intended application. Emphasis is placed on the most typical trial design for
      diagnostic imaging agents that use a comparator to demonstrate that the new IP is
      similar in efficacy to an established standard comparator. Such trials are called
      equivalence, or noninferiority, trials that attempt to show that the new IP is
      not less effective than the comparator by more than a statistically defined
      amount. Importantly, the trial design must not inappropriately favor one
      diagnostic imaging agent over the other. Bias is avoided by the use of a core
      laboratory with expert physicians who are not involved in the trial for
      interpreting and objectively scoring the image sets obtained at the clinical
      trial sites. Clinical trial design must also follow Good Clinical Practice (GCP)
      guidelines. GCP stipulates the clinical trial process, including protocol and
      Case Report Form design, analyses planning, as well as analyzing and preparing
      interim and final clinical trial/study reports.

PMID- 20674593
TI  - The role of the core imaging laboratory in multicenter trials.
AB  - The incorporation of imaging biomarkers and clinical trials is now common.
      Because of the multiple technical, clinical, and regulatory demands to ensure
      high-quality quantitative information, the core laboratory serves as a critical
      intermediary between the study sponsor and the site. It provides unique expertise
      not found in typical clinical research organizations. This expertise goes far
      beyond the passive receipt of images for conductance of central reads of data and
      includes the proactive and early involvement in the selection of sites for
      imaging, the qualification and assistance for managing the local site logistics,
      on-the-fly and active quality control of imaging data in close working
      relationship with sites, and preparation for and conductance of central image
      reads or quantification in a manner which bears up to regulatory scrutiny.

PMID- 20674594
TI  - Operation of a radiopharmacy for a clinical trial.
AB  - Clinical investigations of radiopharmaceuticals are undertaken to advance
      promising compounds toward approval by the Food and Drug Administration (FDA) as
      "legend drugs." This FDA approval requires that the safety and efficacy of the
      investigational drug (ID) be demonstrated through clinical trials. The
      investigational radiopharmaceutical drug service (IRDS) is a pharmacy service
      that plays a critical role in the acquisition, preparation, accountability, and
      distribution of radiopharmaceuticals used in clinical research. Due to their
      radioactive and other unique properties, and their potential role as biomarkers
      or tools in clinical trials of other therapeutic drugs, radiopharmaceutical drugs
      must be managed by a qualified IRDS rather than by a typical pharmacy-based
      investigational drug service (IDS). The IRDS is responsible for establishing
      study-specific procedures for appropriate radiopharmaceutical drug
      accountability, billing, procurement, storage, preparation, dispensing and
      destruction of investigational drugs within the hospital. All drugs, and
      particularly parenteral drug products, must be safe for administration to human
      subjects enrolled in clinical trials regardless of their FDA regulatory status as
      approved or investigational new drug products. The United States Pharmacopeia
      (USP) <797> sterile compounding requirements provides enforceable minimum
      practice and quality standards for compounded sterile preparations of drug
      products based on current scientific information and best sterile compounding
      practices. Consequently, they apply equally to facilities dedicated to IDS and
      IRDS operations. The FDA also regulates drug manufacturing through current Good
      Manufacturing Practices (cGMP). This rule (21CFR Part 212) establishes cGMP
      regulations specific to positron emission tomography radiopharmaceuticals,
      separate from the regular drug cGMP rule (Parts 210 and 211). Compliance with
      regulatory, statutory, and sponsor requirements is a major consideration in the
      operation of a radiopharmacy for clinical trials. Sponsors conduct audits as part
      of the quality assurance of clinical trials. Audits of clinical trial sites by
      the sponsor, sponsor's clinical research organization, institutional review
      board, or FDA always include a detailed review of drug accountability records.
      Audits for radiopharmaceutical drug products typically begin by confirming the
      clinical site is appropriately licensed and authorized to receive, possess,
      store, handle, prepare and administer radiopharmaceuticals. All procedures for
      radiopharmaceutical drug accountability must comply with applicable federal
      regulations and the specific requirements specified by the study sponsor.

PMID- 20674595
TI  - Statistical analysis of clinical trials.
AB  - The randomized clinical trial is widely viewed to be the gold standard for
      evaluation of treatments, diagnostic procedures, or disease screening. The proper
      design and analysis of a clinical trial requires careful consideration of the
      study objectives (eg, whether to demonstrate treatment superiority or
      noninferiority) and the nature of the primary end point. Different statistical
      methods apply when the end point variable is discrete (counts), continuous
      (measurements), or time to event (survival analysis). Other complicating factors
      include patient noncompliance, loss to follow-up, missing data, and multiple
      comparisons when more than 2 treatments are evaluated in the same study. This
      article provides an overview of the basic statistical approaches for analyzing
      clinical trials with binary, continuous or time-to-event outcomes as well as
      methods for handling protocol deviations due to noncompliance and early drop-out.
      Issues surrounding the determination of sample size and power of clinical trials
      are also discussed.

PMID- 20674596
TI  - Food and Drug Administration requirements for testing and approval of new
      radiopharmaceuticals.
AB  - In March 2004, the Food and Drug Administration (FDA) published a report entitled
      Challenge and Opportunity on the Critical Path to New Medical Products in which
      it explained the critical path to medical product development and called for a
      nationwide effort to modernize the critical-path sciences with the aim of moving
      medical product development and patient care into the 21st century. The report
      identified medical imaging and imaging biomarkers as potential clinical
      development tools to facilitate medical product development and to help minimize
      drug attritions and development timelines. Also, in recent years, basic research
      on receptor-based imaging has led to an increase in the new investigational
      radiopharmaceuticals, many of which are in basic research stages in academic
      institutions. It is therefore an opportune time to review the FDA requirements
      for testing and approval of new radiopharmaceuticals to further the cause of
      development and approval of newer medical imaging and therapeutic agents.
      Although the radiopharmaceutical-development process aligns well with the drug
      development process for conventional pharmaceuticals, it has its own challenges
      and unique considerations. For example, unique issues surrounding short-lived
      positron emission tomography drugs have necessitated revisions and refinements to
      the existing regulations. The FDA Modernization Act mandate has finally resulted
      in the publication of new cGMPs (current good manufacturing practice) for
      positron emission tomography drugs. Often, the radiopharmaceutical community is
      not well-informed about the regulatory pathways and scientific basis for the
      regulations they are subjected to. Questions, such as (1) "Do I need an
      investigational new drug (IND) or can I do my investigation under an RDRC
      (radioactive drugs research committee) oversight?" (2) "What type of information
      on radiopharmaceutical product quality is needed for an IND?" (3) "What level of
      cGMPs I am expected to operate under?" (4) "Do I need a traditional IND or can I
      perform studies under an exploratory IND?" (5) "What are the IND-enabling
      pharmacology and toxicology studies?" (6) "Is my practice consistent with
      pharmacy compounding or do I need to file an application with the FDA?", for
      example, are a source of confusion to the radiopharmaceutical community. This
      review provides an overview of FDA's drug development and approval process with
      special emphasis on radiopharmaceuticals and attempts to clarify many regulatory
      issues and questions by providing appropriate discussion and FDA references.

PMID- 20674597
TI  - The institutional review board.
AB  - Several ethical transgressions involving human subjects in scientific research
      during the last century have led to guidelines for acceptable research conduct
      and oversight. Thoughtful examination of these events yielded ethical documents
      whose principles eventually became codified into federal regulations governing
      research. These regulations specify the composition and function of the
      institutional review board (IRB), as well as the criteria by which the IRB judges
      the acceptability of proposed research. Continuous advances in medicine and
      technology generate the need to test new and potentially viable interventions for
      safety and efficacy. These advances in medical science rely heavily on the
      altruism and sometimes heroism of individuals who put their own well being at
      risk for the benefit of others by participating in clinical research experiments.
      It is therefore necessary for researchers to understand the function of the IRB
      and ethics review committees from which approval is required before research in
      human subjects may begin. Understanding the function of the IRB requires an
      appreciation for the rules by which it is governed, as well as the history and
      circumstances that influenced the creation of those rules. Researchers who
      appreciate the IRB's purpose will be better equipped to navigate the labyrinth of
      research guidelines and regulations.

PMID- 20674599
TI  - Painful engagement in deliberate self-harm: The role of conditional goal setting.
AB  - Conditional goal setting is the tendency for people to see attainment of their
      future personal goals as necessary for their well-being. It has been argued that
      this represents an unhealthy way of relating to one's goals, as well as being
      particularly problematic when goals are perceived as unlikely. High conditional
      goal setting has been found to be related to depression and to hopelessness. The
      present study examined conditional goal setting in deliberate self-harm, where
      problematic thinking about the future is very prominent. A group of individuals
      attending hospital for a recent episode of deliberate self-harm (N=25) were
      compared with controls attending hospital for minor injuries (N=25) as well as a
      psychologically disordered but non-suicidal control group (N=25). Participants
      generated goals and rated goal likelihood, the extent to which those goals were
      seen as necessary for their future well-being (conditional goal setting), and
      also the extent to which the goals were seen as sufficient for their future well
      being (goal sufficiency). Deliberate self-harm patients showed a higher degree of
      both conditional goal setting and goal sufficiency than did both of the other
      groups, further confirming the idea of painful engagement with personal goals,
      rather than disengagement, as characterising deliberate self-harm.

PMID- 20674598
TI  - The other allele: exploring the long allele of the serotonin transporter gene as
      a potential risk factor for psychopathy: a review of the parallels in findings.
AB  - Converging evidence suggests that the short allele of the serotonin transporter
      gene polymorphism increases risk for a variety of psychological disorders,
      including depression, anxiety, and alcoholism. Thus, the short allele is
      typically considered the "risk" allele, and findings related to the long allele
      are rarely discussed. However, upon closer examination, findings associated with
      the long allele of the serotonin transporter gene share striking similarities
      with findings from studies of psychopathy. Here, the parallels between findings
      associated with the long/long genotype and findings associated with psychopathic
      traits in the areas of neuropsychology, psychophysiology, hormones, and brain
      imaging are reviewed. It is suggested that the long/long genotype may be a
      potential risk factor for the development of psychopathic traits.

PMID- 20674600
TI  - Community associated methicillin resistant staphylococcus aureus (CA-MRSA)
      infective endocarditis in Italy.

PMID- 20674601
TI  - Polygenic heterogeneity: a complex model of genetic inheritance in psychiatric
      disorders.

PMID- 20674603
TI  - Microglial activation and increased microglial density observed in the
      dorsolateral prefrontal cortex in autism.
AB  - BACKGROUND: In the neurodevelopmental disorder autism, several neuroimmune
      abnormalities have been reported. However, it is unknown whether microglial somal
      volume or density are altered in the cortex and whether any alteration is
      associated with age or other potential covariates. METHODS: Microglia in sections
      from the dorsolateral prefrontal cortex of nonmacrencephalic male cases with
      autism (n = 13) and control cases (n = 9) were visualized via ionized calcium
      binding adapter molecule 1 immunohistochemistry. In addition to a
      neuropathological assessment, microglial cell density was stereologically
      estimated via optical fractionator and average somal volume was quantified via
      isotropic nucleator. RESULTS: Microglia appeared markedly activated in 5 of 13
      cases with autism, including 2 of 3 under age 6, and marginally activated in an
      additional 4 of 13 cases. Morphological alterations included somal enlargement,
      process retraction and thickening, and extension of filopodia from processes.
      Average microglial somal volume was significantly increased in white matter (p =
      .013), with a trend in gray matter (p = .098). Microglial cell density was
      increased in gray matter (p = .002). Seizure history did not influence any
      activation measure. CONCLUSIONS: The activation profile described represents a
      neuropathological alteration in a sizeable fraction of cases with autism. Given
      its early presence, microglial activation may play a central role in the
      pathogenesis of autism in a substantial proportion of patients. Alternatively,
      activation may represent a response of the innate neuroimmune system to synaptic,
      neuronal, or neuronal network disturbances, or reflect genetic and/or
      environmental abnormalities impacting multiple cellular populations.

PMID- 20674602
TI  - Early life programming and neurodevelopmental disorders.
AB  - For more than a century, clinical investigators have focused on early life as a
      source of adult psychopathology. Early theories about psychic conflict and toxic
      parenting have been replaced by more recent formulations of complex interactions
      of genes and environment. Although the hypothesized mechanisms have evolved, a
      central notion remains: early life is a period of unique sensitivity during which
      experience confers enduring effects. The mechanisms for these effects remain
      almost as much a mystery today as they were a century ago. Recent studies suggest
      that maternal diet can program offspring growth and metabolic pathways, altering
      lifelong susceptibility to diabetes and obesity. If maternal psychosocial
      experience has similar programming effects on the developing offspring, one might
      expect a comparable contribution to neurodevelopmental disorders, including
      affective disorders, schizophrenia, autism, and eating disorders. Due to their
      early onset, prevalence, and chronicity, some of these disorders, such as
      depression and schizophrenia, are among the highest causes of disability
      worldwide according to the World Health Organization 2002 report. Consideration
      of the early life programming and transcriptional regulation in adult exposures
      supports a critical need to understand epigenetic mechanisms as a critical
      determinant in disease predisposition. Incorporating the latest insight gained
      from clinical and epidemiological studies with potential epigenetic mechanisms
      from basic research, the following review summarizes findings from a workshop on
      Early Life Programming and Neurodevelopmental Disorders held at the University of
      Pennsylvania in 2009.

PMID- 20674604
TI  - Stability of brain neocortical slice seizure-like activity during low-magnesium
      exposure: Measurement and effect of artificial cerebrospinal fluid temperature.
AB  - Low-magnesium perfusion is an established method for inducing seizure-like
      activity in neocortical slices and is widely utilized as a model of human
      epilepsy. However, many contentious issues remain around optimizing in vitro
      cortical slice experimental protocols. In this study we investigated the
      stability of low-magnesium seizure-like event (SLE) activity at different
      perfusion temperatures; with an aim towards determining whether time-dependent
      effects in this preparation could be attributed to a reduction in tissue
      viability. The results showed that SLE characteristics changed significantly and
      consistently over a 3h recording period, independent of artificial cerebrospinal
      fluid temperature; there was a median increase in event frequency of 61%
      (p<0.001) following 2h of recording which remained elevated after 3h (52%,
      p<0.001). Event amplitude was significantly reduced after 3h (38% reduction,
      p<0.001). Similar effects were recorded whether perfusion temperature was
      maintained at 26 degrees C or 36 degrees C. No evidence was found to implicate a
      reduction in slice viability in these time-dependent changes in SLE behaviour.
      The results indicate that low-magnesium-induced SLE activity is not stable for
      long periods and the likelihood of time-related changes in slice performance must
      be considered when planning and interpreting experiments utilizing the low
      magnesium seizure model.

PMID- 20674605
TI  - High inter-rater reliability in analyzing results of decomposition-based
      quantitative electromyography in subjects with or without neuromuscular disorder.
AB  - Decomposition-based quantitative electromyography (DQEMG) comprises a group of
      methods used to obtain information related to the health of the neuromuscular
      system. Although primarily objective, aspects of the data analysis protocol
      include operator decisions that may impact its reliability and reduce the
      applicability of the technique among multiple users. Thus, the objective of this
      study was to establish the inter-rater reliability of the protocol used for DQEMG
      analysis among five raters. Seventy data files previously obtained using DQEMG
      from healthy control subjects and patients with disorders of the neuromuscular
      system were analyzed by four novice and one experienced rater. Values obtained
      from this analysis were then evaluated for reliability within the novice raters
      and in contrast to the results of the experienced rater to examine the influence
      of the level of rater experience on the results obtained. The majority of the
      parameters associated with the number of motor unit potentials and their
      physiological characteristics were found to be reliable among all raters, with
      moderate-high ICC values observed for both the biceps brachii and first dorsal
      interosseous muscles. The data suggest that the level of rater experience does
      not greatly influence the results obtained and that the analysis can be reliably
      performed by a rater who is given suitable instruction. These findings are
      important particularly given the potential use of DQEMG as an outcome measure in
      multi-center studies.

PMID- 20674606
TI  - Reconstruction and quantitative evaluation of dopaminergic innervation of
      striatal neurons in dissociated primary cultures.
AB  - Repairing the nigrostriatal pathway is expected to become a future treatment
      strategy for Parkinson disease. Our aim is to establish an in vitro model for the
      quantitative analysis of the nigrostriatal projections of dopaminergic neurons
      using primary dissociated neruons. To form the mesencephalic cell region,
      mesencephalic cells derived from rat embryos were plated within an isolation
      wall, which was removed after cell adhesion to the coverslip. After incubation
      for 11 days, the dopaminergic neurites extending to the outside of the
      mesencephalic cell region were mainly axons. Treatment with glial cell line
      derived neurotrophic factor for 11 days significantly promoted the outgrowth of
      dopaminergic axons from the mesencephalic cell region in a concentration
      dependent manner. When striatal cells were plated outside the mesencephalic cell
      region, dopaminergic neurites were remarkably extended to the striatal cell
      region. Moreover, immunocytochemistry for tyrosine hydroxylase and synaptophysin
      revealed that dopaminergic axons formed synapses with striatal neurons. By
      contrast, spinal cells did not increase dopaminergic neurite outgrowth. These
      results indicate that the present method is valuable for evaluating nigrostriatal
      projections in vitro.

PMID- 20674607
TI  - Reverse phase protein microarray technology in traumatic brain injury.
AB  - Antibody based, high throughput proteomics technology represents an exciting new
      approach in understanding the pathobiologies of complex disorders such as cancer,
      stroke and traumatic brain injury. Reverse phase protein microarray (RPPA) can
      complement the classical methods based on mass spectrometry as a high throughput
      validation and quantification method. RPPA technology can address problematic
      issues, such as sample complexity, sensitivity, quantification, reproducibility
      and throughput, which are currently associated with mass spectrometry-based
      approaches. However, there are technical challenges, predominantly associated
      with the selection and use of antibodies, preparation and representation of
      samples and with analyzing and quantifying primary RPPA data. Here we present
      ways to identify and overcome some of the current issues associated with RPPA. We
      believe that using stringent quality controls, improved bioinformatics analysis
      and interpretation of primary RPPA data, this method will significantly
      contribute in generating new level of understanding about complex disorders at
      the level of systems biology.

PMID- 20674608
TI  - [Perioperative multimodal rehabilitation in colorectal surgery: its use is more
      than justified].

PMID- 20674609
TI  - A duplex real-time RT-PCR for the detection of bluetongue virus in bovine semen.
AB  - The control measures prescribed by the World Organization for Animal Health (OIE)
      for international trade in extended semen implicate repeated free testing of the
      donor's blood for bluetongue virus (BTV). The aim of this study was to validate a
      real-time RT-PCR for the direct testing of semen for artificial insemination
      (AI). The amplification of the BTV target was combined with an internal control
      target in duplex format. Optimal RNA recovery and efficient removal of PCR
      inhibitors was established using Trizol-based RNA extraction. The total assay was
      highly repeatable, the preliminary analysis of the specificity was 100% (95% CI:
      92-100%) and the limit of detection was -0.36 log(10)TCID(50) ml(-1) (95% CI: 
      0.53 to -0.18 log(10)TCID(50) ml(-1)) in BTV-8 spiked extended semen. The
      protocol was evaluated using 89 extended semen samples from 19 bulls showing
      typical clinical signs of a natural BTV-8 infection. Forty-eight samples were
      positive, 30 were doubtful and 11 were negative. Infectious BTV-8 was isolated.
      Based on varying real-time RT-PCR results of additional straws from cut-off
      samples it is highly recommended to analyse at least five straws per semen batch
      before declaring semen free of BTV. In conclusion, the partially validated assay
      presented has the potential to be used for the control of semen for international
      trade through direct testing of the semen.

PMID- 20674610
TI  - Influenza virus detection with pentabody-activated nanoparticles.
AB  - A nanoparticle-based immunoassay was developed for the rapid and sensitive
      detection of avian influenza virus (AIV). In this method, AIV-specific pentabody
      (pVHH3B) was conjugated to magnetic nanoparticles (MNPs) and used to capture AIV.
      Gold nanoparticles (GNPs), labelled with the anti-AIV mouse monoclonal antibody
      3C8, were used as a detector. In the presence of target samples, the pentabody
      pVHH3B enriched AIV on the MNPs. Thereafter, mAb 3C8-labelled GNPs (GNPs-mAb3C8)
      bound to MNPs via AIV and were separated using a magnetic field. GNPs in the
      complex catalyzed the oxidation of hydroquinone to quinone, and the OD value of
      quinone was measured. The developed assay displayed substantial signal change
      after incubation in an AIV sample in a concentration-dependent manner. The
      detection limit was 10 ng/ml, which is 10 times more sensitive than conventional
      double-antibody sandwich enzyme-linked immunosorbent assay (DAS-ELISA). In
      conclusion, by combining MNPs and a novel pentabody pVHH3B, this study provided a
      sensitive influenza viral detection assay that has the potential to become a
      rapid, sensitive and inexpensive diagnostic tool for infectious diseases.

PMID- 20674611
TI  - Development and validation of a real-time PCR assay for specific and sensitive
      detection of canid herpesvirus 1.
AB  - A TaqMan-based real-time PCR assay targeting the glycoprotein B-encoding gene was
      developed for diagnosis of canid herpesvirus 1 (CHV-1) infection. The established
      assay was highly specific, since no cross-reactions were observed with other
      canine DNA viruses, including canine parvovirus type 2, canine minute virus, or
      canine adenovirus types 1 and 2. The detection limit was 10(1) and 1.20 x 10(1)
      DNA copies per 10 microl(-1) of template for standard DNA and a CHV-1-positive
      kidney sample, respectively: about 1-log higher than a gel-based PCR assay
      targeting the thymidine kinase gene. The assay was also reproducible, as shown by
      satisfactory low intra-assay and inter-assay coefficients of variation. CHV-1
      isolates of different geographical origins were recognised by the TaqMan assay.
      Tissues and clinical samples collected from three pups which died of CHV-1
      neonatal infection were also tested, displaying a wide distribution of CHV-l DNA
      in their organs. Unlike other CHV-1-specific diagnostic methods, this
      quantitative assay permits simultaneous detection and quantitation of CHV-1 DNA
      in a wide range of canine tissues and body fluids, thus providing a useful tool
      for confirmation of a clinical diagnosis, for the study of viral pathogenesis and
      for evaluation of the efficacy of vaccines and antiviral drugs.

PMID- 20674612
TI  - Evaluation of human intestinal epithelial differentiated cells (Caco-2) for
      replication, plaque formation and isolation of avian influenza viruses.
AB  - Although various cultured cells are used for propagating influenza A viruses, the
      types of cells which can support replication of and plaque production by low
      pathogenic avian influenza (LPAI) viruses without supplementary trypsin are
      limited. In this study, the infectivity and growth kinetics of as well as plaque
      production by LPAI viruses in Caco-2 cells were investigated. The suitability of
      this cell line for virus isolation was examined and compared with virus isolation
      in embryonated chicken eggs. Generation of Caco-2 mediated viral variants, if
      any, was assessed phenotypically and genotypically. It was found that Caco-2
      cells can readily support continued replication of LPAI viruses without
      supplementary trypsin. Viruses replicate to high titer compared to embryonated
      chicken eggs, and more efficiently than in MDCK cells, without trypsin. Also,
      LPAI viruses produced plaques in Caco-2 cells. However, these cells were found to
      be less sensitive than embryonated chicken eggs for virus isolation. Notably, no
      phenotypic and genotypic changes of the viruses were observed during viral
      passages (at least up to 10th passage) in Caco-2 cells. These findings indicate
      that Caco-2 cells may provide an appropriate substrate for studying and
      cultivating AIVs.

PMID- 20674613
TI  - Learning grammatical categories from distributional cues: flexible frames for
      language acquisition.
AB  - Numerous distributional cues in the child's environment may potentially assist in
      language learning, but what cues are useful to the child and when are these cues
      utilised? We propose that the most useful source of distributional cue is a
      flexible frame surrounding the word, where the language learner integrates
      information from the preceding and the succeeding word for grammatical
      categorisation. In corpus analyses of child-directed speech together with
      computational models of category acquisition, we show that these flexible frames
      are computationally advantageous for language learning, as they benefit from the
      coverage of bigram information across a large proportion of the language
      environment as well as exploiting the enhanced accuracy of trigram information.
      Flexible frames are also consistent with the developmental trajectory of
      children's sensitivity to different sources of distributional information, and
      they are therefore a useful and usable information source for supporting the
      acquisition of grammatical categories.

PMID- 20674614
TI  - An automated predator avoidance task in zebrafish.
AB  - Zebrafish are becoming increasingly popular in behavioral neuroscience as
      investigators have started to realize the benefits of sophisticated genetic tools
      specifically developed for this species along with the pharmacological tools
      already available for other laboratory model organisms. The zebrafish has been
      proposed as an in vivo tool for the analysis of vertebrate fear responses as well
      as human psychopathological conditions such as anxiety. We have been developing
      behavioral tasks for zebrafish that could be utilized for screening mutation or
      drug induced changes in fear responses. In this paper we present a modified
      version of a previously developed predator avoidance paradigm that now allows the
      induction and quantification of avoidance reactions that we previously could not
      elicit. Most importantly, in the current paradigm zebrafish are now shown to
      respond to the appearance of a moving image of a sympatric predator, the Indian
      leaf fish, by increasing their distance from the image, a robust reaction that is
      easy to quantify in an automated manner. Unexpectedly, however, another fear
      response, the "diving" response, was seen robustly only at the beginning of the
      test but not in response to the predator stimulus. We discuss the implications of
      these results and conclude that although zebrafish fear responses are complex and
      context dependent, the current paradigm is a significant step towards high
      throughput screening for alterations in fear responses of zebrafish.

PMID- 20674615
TI  - Hemozoin-free Plasmodium falciparum mitochondria for physiological and drug
      susceptibility studies.
AB  - Isolation of mitochondria of high purity and with intact enzymatic activities
      from malaria parasites has proven to be a major obstacle in characterizing the
      parasite mitochondrial physiology. We describe here an improved procedure for the
      isolation of a mitochondrially enriched preparation from the trophozoite stage of
      erythrocytic Plasmodium falciparum, combining disruption by N(2) cavitation and
      differential centrifugation with magnetic removal of hemozoin-associated
      material. These mitochondrial preparations may be used to assay various
      mitochondrial enzyme activities, such as succinate and dihydroorotate
      dehydrogenases, ubiquinol-cytochrome c oxidoreductase, and cytochrome c oxidase.
      They also exhibit a low level of ATPase activity, which is only marginally
      inhibited by classical inhibitors. We have used this preparation to determine the
      susceptibility of mitochondrial activities to drugs and drug candidate compounds
      in both "wild type" and transgenic parasites.

PMID- 20674616
TI  - Evaluation of a rapid molecular screening approach for the detection of toxigenic
      Clostridium difficile in general and subsequent identification of the tcdC
      Delta117 mutation in human stools.
AB  - We have developed and validated a rapid molecular screening protocol for
      toxigenic Clostridium difficile, that also enables the identification of the
      hypervirulent epidemic 027/NAP1 strain. We describe a multiplex real-time PCR
      assay, which detects the presence of the tcdA and tcdB genes directly in stool
      samples. In case of positive PCR results, a separate multiplex real-time PCR
      typing assay was performed targeting the tcdC gene frame shift mutation at
      position 117. We prospectively compared the results of the screening PCR with
      those of a cytotoxicity assay (CTA), and a rapid immuno-enzyme assay for 161
      stool samples with a specific request for diagnosis of C. difficile infection
      (CDI). A total of 16 stool samples were positive by CTA. The screening PCR assay
      confirmed all 16 samples, and gave a PCR positive signal in eight additional
      samples. The typing PCR assay detected the tcdC Delta117 mutation in 2/24 samples
      suggesting the presence of the epidemic strain in these samples. This was
      confirmed by PCR ribotyping and sequencing of the tcdC gene. Using CTA as the
      "gold standard", the sensitivity, specificity, positive predictive value, and
      negative predictive value, for the screening PCR were 100%, 94.4%, 66.7%, and
      100%, respectively. In conclusion, PCR may serve as a rapid negative screening
      assay for patients suspected of having CDI, although the low PPV hamper the use
      of PCR as a standalone test. However, PCR results may provide valuable
      information for patient management and minimising the spread of the epidemic
      027/NAP1 strain.

PMID- 20674617
TI  - Diurnal fluctuations in subjective sleep time in humans.
AB  - Humans have the ability to estimate the passage of time in the absence of
      external time cues. In this study, we subjected 22 healthy males (aged 21.8+/-1.9
      years) to a 40-min nap trial followed by 80min of wakefulness repeated over 28h,
      and investigated the relationship between various sleep parameters and the
      discrepancy (DeltaST) of time estimation ability (TEA) during sleep, defined by
      the difference between actual sleep time (ST) and subjective sleep time (sub-ST)
      in each nap interval. Both ST and sub-ST were significant diurnal fluctuations
      with the peak in the early morning (9h after dim-light melatonin onset time, 2h
      after nadir time of core body temperature rhythm), and subjective sleep duration
      was estimated to be longer than actual times in all nap intervals (sub-ST>ST).
      There were significant diurnal fluctuations in discrepancy (sub-ST-ST) of TEA
      during sleep, and the degree of discrepancy correlated positively with increase
      in the amount of REM sleep and decrease in the amount of slow-wave sleep. These
      findings suggest that human TEA operates at a certain level of discrepancy during
      sleep, and that this discrepancy might be related to the biological clock and its
      associated sleep architecture.

PMID- 20674618
TI  - Effects of reversible pharmacological shutdown of cerebellar flocculus on the
      memory of long-term horizontal vestibulo-ocular reflex adaptation in monkeys.
AB  - The adaptation of the horizontal vestibulo-ocular reflex (HVOR) provides an
      experimental model for motor learning. Two studies, using cats and mice,
      respectively, have recently suggested pharmacologically that the memory of
      adaptation is located multiply in the cerebellum and brainstem. Here, we examined
      the effects of acute cerebellar flocculus shutdown on the adaptation in four
      monkeys. Two hours of 0.11Hz-10 degrees  turntable oscillation while viewing a
      stationary checked-patterned screen through the left-right reversing prism
      decreased the HVOR gains by 0.16, and 3 days of prism wearing combined with 2h of
      daily turntable oscillation decreased the HVOR gains by 0.27. Injections of
      lidocaine into bilateral flocculi did not affect the nonadapted HVOR gains, but
      depressed the visual suppression of the HVOR. They recovered the HVOR gains
      decreased by 2h of training, but very little affected the HVOR gains decreased by
      previous 2 days of training. Injections of control Ringer's solution did not
      affect the gains adapted by 2h or 3 days of training. These results are
      consistent with the previous studies, and suggest that the memory trace of
      adaptation of the HVOR initially resides in the flocculus but later resides,
      presumably, in the vestibular nuclei in the monkey.

PMID- 20674619
TI  - Hydrogen sulfide antagonizes homocysteine-induced neurotoxicity in PC12 cells.
AB  - Hydrogen sulfide (H2S) has been shown to protect neurons against oxidative
      stress. Lower levels of H(2)S as well as accumulation of homocysteine (Hcy), a
      strong risk of Alzheimer's disease (AD), are reported in the brains of AD
      patients. The aim of present study is to explore the protection of H2S against
      Hcy-induced cytotoxicity and apoptosis and the molecular mechanisms underlying in
      PC12 cells. We show that sodium hydrosulfide (NaHS), a H2S donor, protects PC12
      cells against Hcy-mediated cytotoxicity and apoptosis by preventing both the loss
      of mitochondrial membrane potential (MMP) and the increase in intracellular
      reactive oxygen species (ROS) induced by Hcy. NaHS not only promotes the
      expression of bcl-2, but also blocks the down-regulation of bcl-2 by Hcy. These
      results indicate that H2S protects neuronal cells against neurotoxicity of Hcy by
      preserving MMP and attenuating ROS accumulation through up-regulation of bcl-2
      level. Our study suggests a promising future of H2S-based therapies for
      neurodegenerative diseases such as AD.

PMID- 20674620
TI  - Obscure GI bleeding in the East or West: are capsule and double-balloon
      enteroscopy the best?

PMID- 20674621
TI  - Covered or uncovered stents in the colon?

PMID- 20674622
TI  - Gastric wall healing after NOTES procedures: closure with endoscopic clips
      provides superior histological outcome compared with threaded tags closure.
AB  - BACKGROUND: Closure of the transgastric access to the peritoneal cavity is a
      critical step in natural orifice transluminal endoscopic surgery (NOTES).
      OBJECTIVE: To perform a direct comparison of the histological healing post clips
      and threaded tags (T-tags) closure after transgastric NOTES procedures. SETTING: 
      DESIGN AND INTERVENTION: Twelve survival porcine experiments. After standardized
      endoscopic gastric wall puncture, balloon-dilation, and transgastric
      peritoneoscopy, closure of the gastric wall was performed with either clips or T
      tags. Necropsy at 14 days was performed for histological evaluation of 2-mm
      interval transversal cross sections of the gastrotomy site. MAIN OUTCOME
      MEASUREMENTS: Histological healing of the gastric wall opening. RESULTS:
      Endoscopic closure of the gastrotomy was successfully achieved in all 12 animals,
      followed by an uneventful 2-week clinical follow-up. Transmural healing was seen
      in 3 (75%) animals after clip closure compared with only 1 (12.5%) in the group
      with T-tag closure (P = .06). Gastric wall muscular bridging was observed in 4
      (100%) animals with clip closure compared with only 1 (12.5%) in the group with T
      tag closure (P = .01). LIMITATIONS: Animal model with short-term follow-up.
      CONCLUSIONS: Endoscopic clip closure results in a layer-to-layer transmural
      healing of the gastric wall. In contrast, T-tag gastric wall plication impairs
      gastric layer bridging. These findings might guide the future design of new
      endoscopic devices and techniques for gastrotomy closure after NOTES procedures.

PMID- 20674623
TI  - Transvaginal cholecystectomy by using a prototype flexible clip applier.
AB  - BACKGROUND: Currently, no endoscopic clips have been proven to be effective in
      ligating the cystic duct in natural orifice transluminal endoscopic surgery
      (NOTES) hybrid cholecystectomy. OBJECTIVE: To determine the safety and
      feasibility of a prototype endoscopic flexible clip applier, which is the only
      flexible device that deploys a zero-gap clip. DESIGN: Pilot study in a survival
      porcine model. Necropsy was performed at 2 weeks postprocedure. SETTING:
      University of Missouri animal laboratory, Columbia, Missouri. INTERVENTION:
      Transvaginal cholecystectomy was performed on 6 survival pigs using the NOTES
      Toolbox 1.0. MAIN OUTCOME MEASUREMENTS: Safety and feasibility of the described
      instrument. Investigators were asked to fill out a standardized, blinded
      questionnaire on the ease of use and functionality of the flexible clip applier.
      RESULTS: Clipping of the cystic duct was achieved with the flexible clip applier
      in all 6 pigs. The mean time for completion of clipping of the cystic duct was 9
      minutes. Multiple attempts were required to successfully fire the clip in 2 of 6
      pigs. We were unable to visualize the tip of the clip before deployment.
      Difficulty releasing the clip from the applier once fired and challenges in clip
      loading were encountered. The clips were visualized in place at necropsy, with no
      bile leakage, evidence of infection, or injury to surrounding structures seen in
      any cases. LIMITATIONS: Preclinical animal model. CONCLUSION: The prototype
      flexible clip applier showed adequate safety and was feasible in clipping the
      cystic duct in all animals. Design efforts to improve clip visualization,
      loading, and release are underway.

PMID- 20674624
TI  - EUS-guided pancreas ablation: is the sky really the limit?

PMID- 20674625
TI  - Effects of large-balloon dilation on the major duodenal papilla and the lower
      bile duct: histological evaluation by using an ex vivo adult porcine model.
AB  - BACKGROUND: Several articles have reported the usefulness of large-balloon
      dilation after endoscopic sphincterotomy in removing bile duct stones. Its
      histological effect on the duodenal papilla and the lower bile duct, however, is
      not well established. OBJECTIVE: To elucidate the histological consequence of
      large-balloon dilation. DESIGN: Animal experiment. SETTING: A referral center.
      MATERIALS AND INTERVENTIONS: After the evaluation of normal anatomy of the major
      duodenal papilla and the lower bile duct in resected specimens from pigs, large
      balloon dilation (12-20 mm) after small sphincterotomy was performed, and serial
      tissue sections were assessed for morphological changes. MAIN OUTCOME
      MEASUREMENTS: Macroscopic and microscopic findings of the duodenal papilla and
      the lower bile duct after large balloon dilation, with special interest in ductal
      wall disruption and perforation. RESULTS: The porcine specimens were comparable
      in size to humans. Balloons with diameters 12 mm or larger caused disruption of
      the ductal walls, and those 15 mm or larger resulted in perforation of the
      surrounding adipose tissue. The frequency of disruption and perforation increased
      in proportion to the balloon diameters. LIMITATIONS: Other sequelae including
      hemorrhage, pancreatitis, acute inflammatory changes, and late fibrosis could not
      be investigated in our ex vivo porcine model. CONCLUSIONS: Dilation with large
      balloons can tear the bile duct wall and cause potential impairment of sphincter
      function and overdilation of small extrahepatic bile ducts.

PMID- 20674626
TI  - Motion in the direction of making the video capsule our primary endoscope.

PMID- 20674627
TI  - First year of fellowship: lessons learned.

PMID- 20674628
TI  - Where will health care reform take GI practice?

PMID- 20674629
TI  - Integrating urgent multidetector CT scanning in the diagnostic algorithm of
      active lower GI bleeding.

PMID- 20674630
TI  - Closer examination of the nonbleeding visible vessel.

PMID- 20674631
TI  - Endoscopic submucosal dissection for early gastric cancer: is it the best option
      for patients with contraindications to surgery?

PMID- 20674633
TI  - Combination of pharmacologic and endoscopic therapy for preventing variceal
      rebleeding.

PMID- 20674635
TI  - Double-guidewire technique for difficult bile duct cannulation: why not insert a
      prophylactic pancreatic stent?

PMID- 20674636
TI  - Two-step piecemeal resection of larger colorectal polyps: does it make sense?

PMID- 20674637
TI  - Two-step treatment of lateral-spreading tumors.

PMID- 20674638
TI  - Didodecyldimethylammonium bromide (DDAB) induces caspase-mediated apoptosis in
      human leukemia HL-60 cells.
AB  - Didodecyldimethylammonium bromide (DDAB) is widely used for an efficient delivery
      system into mammalian cells. However, the biological activities of DDAB
      nanoparticles in mammalian cells are insufficiently understood. The purpose of
      this study was to establish a critical role of DDAB in cellular response. Here,
      we demonstrate that DDAB is a potent inducer of cell death in a wide range of
      tumor cell lines, wherein leukemia cells (HL-60 and U937) and neuroblastoma cells
      (Neuro2a) were more sensitive to DDAB than carcinoma cells such as HepG2 and Caco
      2 cells. Moreover, in HL-60 cells, treatment with DDAB led to increased numbers
      of apoptotic cells with fragmented DNA (99.6%) and high levels of caspase-3
      activation in comparison to that with actinomycin D. Cotreatment with a caspase-8
      inhibitor (Z-IETD-FMK) or a polyethylene glycol (Mr 2000) (PEG 2000) effectively
      prevented the activation of caspase-3 induced by DDAB. These results suggest that
      DDAB can trigger caspase-3-mediated apoptosis through the extrinsic caspase-8
      pathway and cytotoxic pore formation in cell membrane. Therefore, the present
      findings provide new insight into the biological activity of DDAB to induce
      caspase-mediated apoptosis.

PMID- 20674639
TI  - Predicting the consumption of foods low in saturated fats among people diagnosed
      with Type 2 diabetes and cardiovascular disease. The role of planning in the
      theory of planned behaviour.
AB  - The present study tested the utility of an extended version of the theory of
      planned behaviour that included a measure of planning, in the prediction of
      eating foods low in saturated fats among adults diagnosed with Type 2 diabetes
      and/or cardiovascular disease. Participants (N=184) completed questionnaires
      assessing standard theory of planned behaviour measures (attitude, subjective
      norm, and perceived behavioural control) and the additional volitional variable
      of planning in relation to eating foods low in saturated fats. Self-report
      consumption of foods low insaturated fats was assessed 1 month later. In partial
      support of the theory of planned behaviour, results indicated that attitude and
      subjective norm predicted intentions to eat foods low in saturated fats and
      intentions and perceived behavioural control predicted the consumption of foods
      low in saturated fats. As an additional variable, planning predicted the
      consumption of foods low in saturated fats directly and also mediated the
      intention-behaviour and perceived behavioural control-behaviour relationships,
      suggesting an important role for planning as a post-intentional construct
      determining healthy eating choices. Suggestions are offered for interventions
      designed to improve adherence to healthy eating recommendations for people
      diagnosed with these chronic conditions with a specific emphasis on the steps and
      activities that are required to promote a healthier lifestyle.

PMID- 20674640
TI  - Acute effect of walking on energy intake in overweight/obese women.
AB  - This study examined the acute effect of a bout of walking on hunger, energy
      intake, and appetite-regulating hormones [acylated ghrelin and glucagon-like
      peptide-1 (GLP-1)] in 19 overweight/obese women (BMI: 32.5 +/- 4.3 kg/m2).
      Subjects underwent two experimental testing sessions in a counterbalanced order:
      exercise and rest. Subjects walked at a moderate-intensity for approximately 40
      min or rested for a similar duration. Subjective feelings of hunger were assessed
      and blood was drawn at 5-time points (pre-, post-, 30-, 60-, 120-min post
      testing). Ad libitum energy intake consumed 1-2h post-exercise/rest was assessed
      and similar between conditions (mean +/- standard deviation; exercise: 551.5 +/-
      245.1 kcal [2.31 +/- 1.0 MJ] vs. rest: 548.7 +/- 286.9 kcal [2.29 +/- 1.2 MJ]).
      However, when considering the energy cost of exercise, relative energy intake was
      significantly lower following exercise (197.8 +/- 256.5 kcal [0.83 +/- 1.1 MJ])
      compared to rest (504.3 +/- 290.1 kcal [2.11 +/- 1.2 MJ]). GLP-1 was lower in the
      exercise vs. resting condition while acylated ghrelin and hunger were unaltered
      by exercise. None of these variables were associated with energy intake. In
      conclusion, hunger and energy intake were unaltered by a bout of walking
      suggesting that overweight/obese individuals do not acutely compensate for the
      energy cost of the exercise bout through increased caloric consumption. This
      allows for an energy deficit to persist post-exercise, having potentially
      favorable implications for weight control.

PMID- 20674641
TI  - AMPA receptor mediates mGlu 2/3 receptor antagonist-induced dopamine release in
      the rat nucleus accumbens shell.
AB  - The role of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor
      activation in the regulation of dopamine release by the metabotropic glutamate
      (mGlu) 2/3 receptors in the nucleus accumbens (NAc) shell was investigated using
      an in vivo microdialysis evaluation. The local application of 10 microM of
      LY341495, an mGlu 2/3 receptor antagonist, significantly increased extracellular
      dopamine levels in the NAc shell in freely moving rats. Pretreatment with an AMPA
      receptor antagonist, NBQX (0.3 mg/kg, i.p.) significantly attenuated the increase
      in dopamine release induced by LY341495 application to the basal level, while the
      systemic administration of NBQX alone had no effect on dopamine release in this
      region of the brain. Moreover, the local application of an AMPA receptor
      potentiator, CX546, at 100 or 300 microM also enhanced dopamine release in the
      NAc shell in a concentration-dependent manner. These findings suggest that the
      activation of the postsynaptic AMPA receptor plays a role in mediating the
      regulation of dopamine release by the mGlu 2/3 receptor in the NAc shell.

PMID- 20674642
TI  - Zinc-mediated attenuation of hippocampal mossy fiber long-term potentiation
      induced by forskolin.
AB  - The rise in presynaptic calcium induced by high-frequency stimulation activates
      the calcium-calmodulin-sensitive adenylyl cyclase (AC) 1 followed by the
      induction of long-term potentiation (LTP) at the hippocampal mossy fiber-CA3
      synapse. Zinc is released with glutamate from mossy fiber terminals. However, the
      role of the zinc in mossy fiber LTP is controversial. In the present study, the
      mechanism of zinc-mediated attenuation of mossy fiber LTP was examined in that
      induced by forskolin, an AC activator. Mossy fiber LTP induced by tetanic
      stimulation (100 Hz for 1 s) was attenuated in the presence of 5 microM ZnCl(2),
      whereas that induced by forskolin under test stimulation (0.1 Hz) was not
      attenuated. Forskolin-induced mossy fiber LTP was attenuated by perfusion with
      100 microM ZnCl(2) prior to the induction. However, the zinc (100 microM) pre
      perfusion did not attenuate mossy fiber LTP induced by Sp-cAMPS, an activator of
      protein kinase A, under test stimulation. Zinc is necessary to be taken up into
      mossy fiber boutons for effectively inhibiting AC activity. In hippocampal slices
      labeled with ZnAF-2 DA, a membrane-permeable zinc indicator, intracellular ZnAF-2
      signal was increased during tetanic stimulation in the presence of 5 microM
      ZnCl(2), but not under test stimulation. Intracellular ZnAF-2 signal was
      increased under test stimulation in the presence of 100 microM ZnCl(2). These
      results suggest that zinc taken up into mossy fibers attenuates forskolin-induced
      mossy fiber LTP via inhibition of AC activity. The significance of endogenous
      zinc uptake by mossy fibers is discussed focused on tetanus-induced mossy fiber
      LTP.

PMID- 20674643
TI  - Association of IKBA gene polymorphisms with the development of asthma.
AB  - Nuclear factor-kappaB (NF-kappaB) orchestrates the expression of genes
      responsible for airway inflammation and remodeling in asthma. The activity of NF
      kappaB is tightly regulated by IKBA, which may be modulated by genetic
      polymorphisms of the IKBA gene. We investigated the association between asthma
      susceptibility and IKBA gene polymorphisms in a Korean population. Genotyping was
      performed in BA (bronchial asthma) and NC (normal control). We measured reverse
      transcription-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent
      assay, and luciferase reporter assays, respectively. A -673A>T (rs2233407) was
      associated with asthma development in subjects with atopic asthma (odds ratio =
      0.56, p = 0.004). The IKBA mRNA level was higher in B-cell lines with the
      rs2233407 TT genotype compared with those with the AA genotype (p = 0.024). The
      luciferase activity of the rs2233407 T genotype was higher than that of the A (p
      = 0.002). The cytoplasmic levels of total IKBA and IKBA [p-S32] were higher in B
      cell lines of the rs2233407 TT genotype than those of the AA (p = 0.016 and p =
      0.036, respectively), whereas nuclear NF-kappaB activity in cells with the IKBA
      rs2233407 AA genotype was higher than in cells with the AA (p = 0.038). The IKBA
      rs2233407 A>T polymorphism may predispose individuals to the development of
      atopic asthma via regulation of IKBA gene expression at the transcriptional
      level.

PMID- 20674644
TI  - Renal crystal formation after combined or sequential oral administration of
      melamine and cyanuric acid.
AB  - We evaluated renal melamine-cyanurate crystal spherulite formation after single
      and repeated ingestion of both melamine (MEL) and cyanuric acid (CYA) in catfish
      and trout. MEL and CYA were co-administered orally over a range of doses, 0.1
      20mg/kg body weight (bw) of each compound, either once or repeatedly for 4, 14 or
      28 days (d). In catfish, the No Observable Adverse Effects Levels (NOAELs) for
      crystal formation for single, 4d or 14 d dosing were 10, 2.5 and 0.5mg/kg bw,
      respectively. In trout, the respective NOAELs were 2.5, 2.5 and 0.5mg/kg bw. No
      renal crystals formed in catfish fed 0.1mg/kg bw of each compound for 28 d.
      Sequential administration of 20mg/kg bw of MEL followed by 20mg/kg bw of CYA or
      vise-versa, with waiting periods of 1, 3, 7, 14 or 21 d between compound dosing
      also induced renal crystal formation in fish. These studies show that both
      catfish and trout are sensitive, non-mammalian models, for renal crystal
      formation following MEL and CYA ingestion. Since fish generally excrete chemicals
      more slowly than mammals, they may provide a "worst case scenario" model for
      higher risk populations, such as infants or persons with compromised renal
      function.

PMID- 20674645
TI  - Pluripotent stem cell derived hepatocyte like cells and their potential in
      toxicity screening.
AB  - Despite considerable progress in modelling human liver toxicity, the requirement
      still exists for efficient, predictive and cost effective in vitro models to
      reduce attrition during drug development. Thousands of compounds fail in this
      process, with hepatotoxicity being one of the significant causes of failure. The
      cost of clinical studies is substantial, therefore it is essential that
      toxicological screening is performed early on in the drug development process.
      Human hepatocytes represent the gold standard model for evaluating drug toxicity,
      but are a limited resource. Current alternative models are based on immortalised
      cell lines and animal tissue, but these are limited by poor function, exhibit
      species variability and show instability in culture. Pluripotent stem cells are
      an attractive alternative as they are capable of self-renewal and differentiation
      to all three germ layers, and thereby represent a potentially inexhaustible
      source of somatic cells. The differentiation of human embryonic stem cells and
      induced pluripotent stem cells to functional hepatocyte like cells has recently
      been reported. Further development of this technology could lead to the scalable
      production of hepatocyte like cells for liver toxicity screening and clinical
      therapies. Additionally, induced pluripotent stem cell derived hepatocyte like
      cells may permit in vitro modelling of gene polymorphisms and genetic diseases.

PMID- 20674646
TI  - Post-translational modification by SUMO.
AB  - Post-translational modifications (PTMs) are chemical alterations to a protein
      following translation, regulating stability and function. Reversible
      phosphorylation is an example of an important and well studied PTM involved in a
      number of cellular processes. SUMOylation is another PTM known to modify a large
      number of proteins and plays a role in various cellular processes including: cell
      cycle regulation, gene transcription, differentiation and cellular localisation.
      Therefore, understanding the role of SUMOylation in cell biology may allow the
      development of more efficient models, important in streamlining the drug
      discovery process. This review will focus on protein SUMOylation and its role in
      stem cell and somatic cell biology.

PMID- 20674647
TI  - Evaluation of the safety of the dietary antioxidant ergothioneine using the
      bacterial reverse mutation assay.
AB  - The dietary antioxidant L-(+)-ergothioneine was tested for its potential
      mutagenic activity using the bacterial reverse mutation assay. The experiments
      were carried out using histidine-requiring auxotrophic strains of Salmonella
      typhimurium (Salmonella typhimurium TA98, TA100, TA1535 and TA1537), and the
      tryptophan-requiring auxotrophic strain of Escherichia coli (Escherichia coli WP2
      uvrA) in the presence and absence of a post-mitochondrial supernatant (S9)
      prepared from livers of phenobarbital/beta-naphthoflavone-induced rats. The
      revertant colony numbers of vehicle control plates with and without S9 Mix were
      within the corresponding historical control data ranges. The reference mutagen
      treatments (positive controls) showed the expected, biologically relevant
      increases in induced revertant colonies in all experimental phases in all tester
      strains. No biologically relevant increases were observed in revertant colony
      numbers of any of the five test strains following treatment with L-(+)
      ergothioneine at any concentration level, either in the presence or absence of
      metabolic activation (S9 Mix) in the performed experiments. On the basis of the
      data reported, it can be concluded that L-(+)-ergothioneine did not induce gene
      mutations by base pair changes or frameshifts in the genome of the strains used.
      Thus L-(+)-ergothioneine has no mutagenic activity on the applied bacteria tester
      strains under the test conditions used in this study. Research is continuing to
      define the role of L-(+)-ergothioneine in disease pathophysiology. Further
      studies on its safety are suggested.

PMID- 20674648
TI  - Mechanism underlying the olfactory disturbance induced by an intraperitoneal
      injection of tributyltin chloride in rats.
AB  - Acute intoxication by tributyltin compounds has been known to induce olfactory
      disturbances, although the underlying mechanism remains unclear. This study
      investigates the acute effect of tributyltin chloride (TBTC) on the olfactory
      bulb in rats. The time-course characteristics of the intra-olfactory
      concentration of TBTC, the histopathological changes of the olfactory bulb and
      the olfactory function were examined for 96 h after a single intraperitoneal
      injection of 2.5 mg/kg of TBTC. The olfactory function was evaluated by the
      discriminating ability for a cycloheximide solution which has an unpleasant odor
      for rats. The concentration of TBTC in the olfactory bulb, which was measured
      using gas chromatography/mass spectrometry, quickly increased to a peak value
      within 24 h and then decreased. The viable cell number significantly decreased
      after the TBTC administration in the mitral cell layer and granule cell layer of
      the olfactory bulb, while apoptotic cells significantly increased in these areas
      at the same time. Hyposmia was evident 96 h after the TBTC injection, although
      olfactory testing could not been performed until that time because of anorexia.
      These results suggest that intraperitoneally injected TBTC was promptly
      transferred to the olfactory bulb through the blood-brain barrier, induced
      apoptosis of the cells in the olfactory bulb and finally elicited the olfactory
      disturbance.

PMID- 20674649
TI  - Reliability of physical examination tests used in the assessment of patients with
      shoulder problems: a systematic review.
AB  - BACKGROUND: Shoulder pain is a common clinical problem, and numerous tests are
      used to diagnose structural pathology. OBJECTIVES: To systematically review the
      reliability of physical examination procedures used in the clinical examination
      of patients with shoulder pain. DATA SOURCES: MEDLINE, PEDro, AMED, PsychInfo,
      Cochrane Library (2009) and CINAHL were searched from the earliest record on the
      database to June 2009. STUDY ELIGIBILITY CRITERIA: Reliability studies that
      included any patients with shoulder pain were analysed for their quality and
      reliability results. STUDY APPRAISAL AND SYNTHESIS METHODS: Pre-established
      criteria were used to judge the quality of the studies (high quality >60% methods
      score) and satisfactory levels of reliability (kappa or intraclass correlation
      coefficient > or =0.85, sensitivity analysis 0.70). A qualitative synthesis was
      performed based on levels of evidence. RESULTS: Thirty-six studies were included
      with a mean methods score of 57%. Seventeen studies were deemed to be of high
      quality; high-quality studies were less likely to meet the pre-agreed level of
      reliability. The majority of studies indicated poor reliability for all
      procedures investigated. LIMITATIONS: Overall, the evidence regarding reliability
      was contradictory. CONCLUSIONS AND IMPLICATIONS: There is no consistent evidence
      that any examination procedure used in shoulder assessments has acceptable levels
      of reliability. Alternate methods of classification which are reliable should be
      used to classify patients with shoulder problems.

PMID- 20674650
TI  - Influence of self-reported socio-economic status on lung function of adult
      Nigerians.
AB  - OBJECTIVES: Low socio-economic status is known to be associated with reduced lung
      function in childhood and early adulthood, and an increased risk of
      cardiovascular disease in older adults. The lung function of people in developing
      nations is known to be lower than that of their counterparts in developed
      nations. This study assessed whether childhood socio-economic status is related
      to lung function in adults in Nigeria. DESIGN: Cross-sectional study. SETTING:
      Ife central local government, Ile-Ife, Nigeria. PARTICIPANTS: One thousand nine
      hundred and thirty healthy adults aged 40 to 80 years took part in the study.
      Forced vital capacity (FVC) and forced expiratory volume in 1second (FEV(1)) were
      measured with a spirometer, and peak expiratory flow (PEF) was measured with a
      mechanical peak expiratory flow meter. The socio-economic status questionnaire
      gave equal importance to education, occupation and family income. Based on the
      score, the subjects were classified as lower, middle or higher status. MAIN
      OUTCOME MEASURES: Spirometry, assessment of peak flow meter and questionnaire to
      assess socio-economic status. RESULTS: The results showed a difference between
      the group with the highest socio-economic status and the other two groups [mean
      (standard deviation) FVC: high 3.63l (0.33), middle 3.57l (0.41), low 3.38l
      (0.35)]. The mean difference between the high and middle socio-economic groups
      was 0.07l [95% confidence interval (CI) 0.02 to 0.11]. A similar difference
      existed for FEV(1): high 3.16l (0.28), middle 3.06l (0.31), low 2.94l (0.34). The
      mean difference between the high and middle socio-economic groups was 0.11l (95%
      CI 0.07 to 0.15). Values for PEF were: high 404.30l/second (35.98), medium
      390.56l/second (41.53), low 376.03l/second (45.81). The mean difference between
      the high and medium socio-economic groups was 13.74l/second (95% CI 8.42 to
      19.06). There was a weak but significant association between socio-economic
      status and FVC (r=0.28), FEV(1) (r=0.26) and PEF (r=0.25). CONCLUSION: Self
      reported low socio-economic status is associated with lower lung function among
      adult Nigerians. This may increase their risk for respiratory and cardiovascular
      disease.

PMID- 20674651
TI  - A national framework for supporting improvements in the physiotherapy assessment
      and management of low back pain: the Scottish experience.
AB  - BACKGROUND: Similar to other countries worldwide, Scotland lacked a national view
      of whether the quality of the physiotherapy management of low back pain was
      compliant with national guidelines. Anecdotal evidence suggested that standards
      of care varied considerably despite the wide availability of clinical guidelines
      to clinicians. AIM: To develop a framework that supports National Health Service
      (NHS) Scotland in providing consistently applied high-quality physiotherapy
      assessment and management of low back pain in line with guideline
      recommendations. DESIGN: Prospective, multicentred national study, data
      collection and improvement phase. SETTING: All NHS boards in Scotland (n=14) plus
      two private provider sites. PARTICIPANTS: One hundred and eighty-six individual
      NHS sites and two private providers of services to patients with low back pain.
      METHOD: A national dataset was developed from evidence- and consensus-based
      guideline sources. All sites collected data (two 5-week periods) over 1 year
      (2008-2009) using a web-based database. This was interspersed by an improvement
      phase during which required improvements were considered and implemented. Issues
      were shared through a national network and national meeting. RESULTS: Data from
      2147 patients showed improvements in the documented physiotherapy management of
      low back pain over the two cycles. All participants developed and implemented
      remedial action plans based on the results of the first cycle. CONCLUSION: It is
      possible to implement a framework, which is led nationally but driven and owned
      locally, supporting physiotherapists in an active programme of locally determined
      improvement. However, although process and outcome are linked, the direct impact
      of this initiative on patient outcome is not known.

PMID- 20674652
TI  - Sources of stress and psychological morbidity among undergraduate physiotherapy
      students.
AB  - OBJECTIVES: Professional education can be a stressful experience for some
      individuals, and may impact negatively on emotional well-being and academic
      performance. Psychological morbidity and associated sources of stress have not
      been investigated extensively in physiotherapy students. This study explored
      sources of stress, psychological morbidity and possible associations between
      these variables in undergraduate physiotherapy students. DESIGN: A questionnaire
      based survey. The Undergraduate Sources of Stress Questionnaire was used to
      identify sources of stress, and the General Health Questionnaire-12 (GHQ-12) was
      used to rate the prevalence of psychological morbidity, using a conservative GHQ
      threshold of 3 to 4 to determine probable 'cases'. Uni- and multivariate tests of
      correlation were used to analyse the data. SETTING: An Irish educational
      institution. PARTICIPANTS: One hundred and twenty-five physiotherapy
      undergraduate students. RESULTS: More than one-quarter of all students (27%)
      scored above the GHQ threshold, indicating probable psychological morbidity. This
      is higher than the level of psychological morbidity reported by the general
      population. Regression analysis showed that academic (beta=0.31, P<0.001) and
      personal (beta=0.50, P<0.001) sources of stress subscales were significant
      coefficients, explaining 48% of the variance in psychological morbidity after
      controlling for part-time employment and hours spent studying. Individual
      significant items from these subscales were stressful events (beta=0.24,
      P=0.004), mood (beta=0.43, P< or =0.001) and overall level of stress (beta=0.35,
      P< or =0.001). CONCLUSIONS: The results highlighted the emotional vulnerability
      of a significant proportion of physiotherapy students, with academic and personal
      issues being the greatest concern. While personal causes of stress such as
      stressful events and mood are more difficult to control, manipulation of
      curricular factors may have positive effects on academic sources of stress.

PMID- 20674653
TI  - The influence of psychological factors on pre-operative levels of pain intensity,
      disability and health-related quality of life in lumbar spinal fusion surgery
      patients.
AB  - OBJECTIVES: To assess the extent to which perceived pain and psychological
      factors explain levels of disability and health-related quality of life (HRQOL)
      in patients scheduled for lumbar fusion surgery, and to test the hypothesis that
      relationships between pain intensity, mental health, fear of movement/(re)injury,
      disability and HRQOL are mediated by cognitive beliefs and appraisals. DESIGN:
      Cross-sectional, correlation study. SETTING: Orthopaedic outpatient setting in a
      tertiary hospital. PARTICIPANTS: One hundred and seven chronic back pain patients
      scheduled for lumbar fusion surgery. MEASURES: Visual analogue scale for pain
      intensity, Short Form 36 mental health subscale, Tampa Scale for Kinesiophobia,
      Back Beliefs Questionnaire, Self-efficacy Scale, Coping Strategy Questionnaire,
      Oswestry Disability Index and European Quality of Life Questionnaire. RESULTS:
      The group effect of multiple mediators significantly influenced the relationships
      between pain intensity and mental health, fear of movement/(re)injury, functional
      disability and HRQOL. Pain catastrophising significantly mediated the
      relationship between pain intensity and mental health, control over pain
      significantly mediated the relationship between mental health and functional
      disability, self-efficacy and pain outcome expectancy significantly mediated the
      relationship between mental health and HRQOL, and self-efficacy also
      significantly mediated the relationship between pain intensity, fear of
      movement/(re)jury and functional disability. The model explained 28, 30, 52 and
      42% of the variation in mental health, fear of movement/(re)injury, functional
      disability and HRQOL, respectively. CONCLUSIONS: This study highlights the strong
      influence and mediation roles of psychological factors on pain, mental health,
      fear of movement/(re)injury, disability and HRQOL in patients scheduled for
      lumber fusion. Future research should focus on screening as well as pre- and post
      operative interventions based on these psychological factors for the potential
      improvement of lumber fusion surgery outcomes.

PMID- 20674654
TI  - Long-term reliability of the incremental shuttle walking test in clinically
      stable cardiovascular disease patients.
AB  - OBJECTIVE: The incremental shuttle walking test (ISWT) is a valuable tool for
      assessing changes in patients' functional capacity during cardiac rehabilitation.
      However, studies have only assessed its test-retest reliability in the short
      term. The purpose of this study was to examine long-term test-retest reliability
      of the ISWT in clinically stable cardiac patients. DESIGN: Test-retest
      reliability assessment. SETTING: Continuous, community-based phase IV cardiac
      rehabilitation centre. PARTICIPANTS: Thirty patients with cardiovascular disease
      (15 males, 15 females; age 55 to 80 years) volunteered to participate in the
      study. INTERVENTIONS: Participants undertook two ISWTs, a minimum of 8 weeks
      apart. MAIN OUTCOME MEASURES: ISWT performance in metres. RESULTS: Overall, the
      mean distance walked in the pre-test was 502+/-161m and this did not differ from
      test to retest. The intraclass correlation coefficient was 0.80, indicating good
      test-retest reliability. Using the Bland and Altman method, there was a small
      mean test-retest difference (-7m). The 95% limits of agreement were large,
      ranging from -203m to 189m. CONCLUSIONS: Over long test-retest durations, there
      appears to be no learning effect in the ISWT, negating the need for a practice
      walk. The long-term random variation in the ISWT test is larger than in previous
      studies, probably due to greater physiological and psychological variation in the
      participants over 8 weeks compared with that seen in day-to-day testing. Factors
      influencing long-term test-retest reliability of the ISWT require further
      elucidation.

PMID- 20674655
TI  - An investigation of the use of passive movements in intensive care by UK
      physiotherapists.
AB  - OBJECTIVES: To investigate the current use of passive movements (PMs) by National
      Health Service (NHS) physiotherapists working with sedated and ventilated
      patients in critical care settings. DESIGN: Postal questionnaire. SETTING: All
      open NHS critical/intensive care units in England, Northern Ireland, Scotland and
      Wales. PARTICIPANTS: Physiotherapists working in UK NHS critical/intensive care
      units. RESULTS: Questionnaires were posted to 246 physiotherapists working in
      intensive care units; 165 (67%) were returned. One hundred and fifty-two
      respondents routinely treated ventilated and sedated patients, of which 151 (99%)
      reported utilising PMs. They were used most commonly (>70%) in patients admitted
      to critical care with medical, neurological or surgical problems. Respondents
      reported using a median of five repetitions of PMs once daily, and the majority
      of respondents took joints to the end of range (>78%). Joints most commonly
      treated included the shoulder, hip, knee, elbow and ankle. Heart rate and blood
      pressure were monitored by over 84% of respondents during treatment. CONCLUSIONS:
      Whilst there is little empirical evidence to underpin the use of PMs, this study
      found that PMs were used regularly by 99% of respondents working in NHS critical
      care settings. Further work is now needed to evaluate the immediate and long-term
      effects of PMs in critically ill patients to inform and develop future practice.

PMID- 20674656
TI  - Comparison of the 6-minute walk distance test performed on a non-motorised
      treadmill and in a corridor in healthy elderly subjects.
AB  - OBJECTIVE: To compare the 6-minute walk distance (6MWD) test performed on a non
      motorised treadmill (6MWD-T) with the 6MWD test performed in a corridor (6MWD-C)
      in healthy elderly subjects. PARTICIPANTS: Sixteen healthy elderly individuals.
      DESIGN: Participants performed three 6MWD-T tests and three 6MWD-C tests on two
      different days. OUTCOME MEASURES: Distance walked was recorded in metres.
      Perceived exertion and leg fatigue were rated on the modified Borg scale before
      and after each test. RESULTS: Using the Bland and Altman limits of agreement
      analysis method, the mean difference between the two methods was 153.3m (limits
      of agreement: 28 to 278). The mean difference between days 1 and 2 for the 6MWD-C
      test was -7.2m (limits of agreement: -45.4 to 30.8), and the mean difference
      between days 1 and 2 for the 6MWD-T test was -1.6m (limits of agreement: -64.0 to
      60.7). The mean difference between the first and second repetitions of the 6MWD-C
      test was -5m (limits of agreement: -41 to 31), and the mean difference between
      the first and second repetitions of the 6MWD-T test was -17m (limits of
      agreement: -85 to 51). CONCLUSIONS: The 6MWD-C and 6MWD-T tests are not
      interchangeable. However, the results showed good test-retest reliability between
      days and between test repetitions for both tests. Therefore, the 6MWD-T test may
      offer an alternative option to the 6MWD-C test when a 30-m corridor is not
      available. These findings may have implications for execution of the 6MWT-T test
      within cardiac and pulmonary rehabilitation.

PMID- 20674657
TI  - Experiences of new physiotherapy lecturers making the shift from clinical
      practice into academia.
AB  - OBJECTIVES: To explore the experiences of physiotherapists making the transition
      from practising physiotherapist to physiotherapy lecturer in higher education,
      and to understand these experiences in order to inform an explanation of ways of
      managing this transition. DESIGN: A qualitative, interpretive research design
      using semi-structured interviews. The interviews were transcribed, read and
      thematically analysed. PARTICIPANTS: Using purposive sampling, eight
      physiotherapy lecturers within their first 4 years of teaching in higher
      education at one North West university were interviewed. FINDINGS: Despite having
      previous successful clinical careers, participants initially struggled to make
      the transition, characterised by initial feelings of uncertainty and inadequacy.
      Participants took between 1.5 and 3 years to socialise into their new academic
      role, adopting a new professional identity as a physiotherapy academic. Informal
      learning and peer support were the most valued mechanisms of support, more so
      than a formally structured mentoring process. Challenges of dual professionalism
      and tensions emerged regarding the expected academic roles of a lecturer.
      Confidence in developing a pedagogy for higher education and contributing to
      established communities of practice were key indicators of successfully making
      the shift to becoming an academic. CONCLUSIONS: To meet the new physiotherapy
      lecturers' needs and build up confidence in higher education, more effective
      induction strategies are worthy of endeavour. More formal training designed to
      specifically address those aspects of transition particular to clinicians making
      the shift from clinical practice into academia is suggested.

PMID- 20674658
TI  - The 'lone ranger': a descriptive study of physiotherapy practice in Australian
      emergency departments.
AB  - OBJECTIVES: Physiotherapy services have recently been introduced to Australian
      emergency departments in an attempt to address service delivery issues such as
      access block. This study aimed to determine the roles, including those relating
      to extended scope practice, currently undertaken by physiotherapists in
      Australian emergency departments. DESIGN: Descriptive cross-sectional design. An
      Internet-based survey, containing 37 items to access demographic and perceptual
      data, was distributed to Australian emergency department physiotherapists between
      8 February and 30 April 2009. Twenty-eight of these questions generated
      categorical data, which were analysed using frequency distributions. Thematic
      analysis was undertaken for the nine questions that generated text responses.
      PARTICIPANTS: Participants were included if they were registered Australian
      physiotherapists working in an emergency department as part of the
      multidisciplinary team, and did not provide on-call service to the emergency
      department. Twenty-eight Australian emergency department physiotherapists met the
      inclusion criteria and completed the survey. RESULTS: The respondents were
      predominantly females working on a full-time basis in the emergency department.
      Responses indicated that the role is subject to time pressures with an emphasis
      on diagnosis and discharge planning. One respondent described emergency
      department physiotherapists as 'lone rangers' due to their autonomous work.
      Australian emergency department physiotherapists are not currently performing
      extended scope tasks, as many are prohibited under Australian legislation, but it
      is also unclear which tasks might be classified as extended scope. CONCLUSION:
      Australian emergency department physiotherapists currently perform traditional
      physiotherapy roles in a non-traditional work environment. The role is aligned
      with musculoskeletal physiotherapy; however, there is a degree of holistic care
      involved, particularly for elderly patients. The effect that an emergency
      department physiotherapy service has on health outcomes is not known, but the
      study participants indicated that they believe their service has system-wide
      benefits.

PMID- 20674659
TI  - What are the perceived needs of Pakistani women in the North west of England in
      relation to physiotherapy, and to what extent do they feel their needs are being
      met?
AB  - OBJECTIVE: To gain an insight into the needs of female Pakistani service users in
      relation to physiotherapy. DESIGN: A qualitative research design was utilised,
      drawing on ethnographic traditions and including ethnographic interviews. The
      interviews were transcribed and the data were analysed using thematic analysis.
      SETTING: A venue of the service user's own choosing in one geographical area of
      the North west of England. PARTICIPANTS: Six, Pakistani, Muslim female patients
      who had recently received physiotherapy from a range of specialisms. Five
      participants came to the UK from Pakistan, and one participant of Pakistani
      heritage came to the UK from East Africa. An interpreter was used in four of the
      six interviews. FINDINGS: Four main themes emerged from data analysis: issues of
      gender; language issues including the subthemes of crosscultural communication,
      time and materials; role of exercise; and acquiescence. CONCLUSIONS: It appears
      that physiotherapy provision for female patients with Pakistani backgrounds may
      be failing to meet their needs, which may affect compliance. In order to address
      these issues, culturally competent health care needs to be provided and the
      following points are worthy of consideration:

PMID- 20674661
TI  - Color categories affect pre-attentive color perception.
AB  - Categorical perception (CP) of color is the faster and/or more accurate
      discrimination of colors from different categories than equivalently spaced
      colors from the same category. Here, we investigate whether color CP at early
      stages of chromatic processing is independent of top-down modulation from
      attention. A visual oddball task was employed where frequent and infrequent
      colored stimuli were either same- or different-category, with chromatic
      differences equated across conditions. Stimuli were presented peripheral to a
      central distractor task to elicit an event-related potential (ERP) known as the
      visual mismatch negativity (vMMN). The vMMN is an index of automatic and pre
      attentive visual change detection arising from generating loci in visual
      cortices. The results revealed a greater vMMN for different-category than same
      category change detection when stimuli appeared in the lower visual field, and an
      absence of attention-related ERP components. The findings provide the first clear
      evidence for an automatic and pre-attentive categorical code for color.

PMID- 20674662
TI  - Influence of soil properties on molybdenum uptake and elimination kinetics in the
      earthworm Eisenia andrei.
AB  - This study aimed at determining the uptake and elimination kinetics of molybdenum
      in the earthworm Eisenia andrei, and the influence of soil properties on
      molybdenum bioaccumulation. Three natural and four artificial soils were spiked
      at concentrations of 10 and 100 microg Mo g(-1) dry soil. Earthworms were exposed
      individually to spiked soils and sampled at different time intervals for 21 d.
      Remaining earthworms were transferred to non-spiked soil to determine
      elimination, also for 21 d. Uptake and elimination rate constants and
      bioaccumulation factors (BAFs) were calculated using a one-compartment model, and
      related to total, water and CaCl2 extractable molybdenum concentrations in soil.
      Molybdenum was rapidly accumulated by the earthworms with uptake rate constants
      between 0.05 and 1.70 g dry soil g(-1) dry earthworm d(-1), and equilibrium
      generally was reached within 10 d. Molybdenum was not strongly bioaccumulated
      (BAF<or=4). Mo availability and bioaccumulation in earthworms was mainly affected
      by soil pH and organic carbon content.

PMID- 20674663
TI  - A factor(s) secreted from MIN-6 beta-cells stimulates differentiation of
      definitive endoderm enriched embryonic stem cells towards a pancreatic lineage.
AB  - In the mouse the developing pancreas is controlled by contact with, and
      signalling molecules secreted from, surrounding cells. These factors are best
      studied using explant cultures of embryonic tissue. The present study was
      undertaken to determine whether embryonic stem (ES) cells could be used as an
      alternative model in vitro system to investigate the role of cell-cell
      interactions in the developing pancreas. Transwell culture experiments showed
      that MIN-6 beta-cells secreted a factor or factors that promoted differentiation
      of ES cell derived definitive endoderm enriched cells towards a pancreatic fate.
      Further studies using MIN-6 condition medium showed that the factor(s) involved
      was restricted to MIN-6 cells, could be concentrated with ammonium sulphate, and
      was sensitive to heat treatment, suggesting that it was a protein or peptide.
      Further analyses showed that insulin or proinsulin failed to mimic the effects of
      the conditioned media. Collectively, these results suggest that beta-cells
      secrete a factor(s) capable of controlling their own differentiation and
      maturation. The culture system described here presents unique advantages in the
      identification and characterisation of these factors.

PMID- 20674664
TI  - Gonadotropins and gonadotropin receptors--evolutional genetics, signalling
      mechanisms, extra gonadal function and roles in oncogenesis.

PMID- 20674665
TI  - Berberine attenuates lipopolysaccharide-induced extracelluar matrix accumulation
      and inflammation in rat mesangial cells: involvement of NF-kappaB signaling
      pathway.
AB  - BACKGROUND: Our previous studies demonstrated that berberine could improve the
      renal function in rats and mice with diabetic nephropathy (DN) and inhibit
      extracellular matrix (ECM) component, fibronectin (FN) expression in rat
      mesangial cells (MCs) cultured under high glucose. However, the molecular
      mechanisms have not been fully elucidated. OBJECTIVE: To explore the potential
      mechanisms of berberine in the treatment of DN, we investigated the effects of
      berberine on lipopolysaccharide (LPS)-induced nuclear factor-kappa B (NF-kappaB)
      activation and its downstream inflammatory mediators, such as intercellular
      adhesion molecule-1 (ICAM-1), transforming growth factor-beta 1 (TGF-beta1),
      inducible nitric oxide synthase (iNOS) and fibronectin (FN) protein expression in
      rat MCs. METHOD: Cell proliferation was determined by 3-(4,5-dimethylthiazol-2
      yl)-2,5-diphenyltetrazolium bromide (MTT). The activation of NF-kappaB was
      detected by Western blot and confocal microscopy. The protein levels of ICAM-1,
      TGF-beta1, iNOS and FN in rat MCs were detected by Western blot. RESULTS: Our
      results revealed that berberine significantly suppressed LPS-induced cell
      proliferation and inhibited LPS-induced NF-kappaB nuclear translocation in MCs,
      as well as protein expression of ICAM-1, TGF-beta1, iNOS and FN. CONCLUSION:
      Berberine significantly repressed LPS-induced cell proliferation and FN
      expression in rat MCs through inhibiting the activation of NF-kappaB signaling
      pathway and protein expression of its downstream inflammatory mediators. The
      ameliorative effects of berberine on DN might be associated with this inhibition
      effect on NF-kappaB signaling pathway which was independent of its hypoglycemic
      effect.

PMID- 20674666
TI  - Protein kinase D activation stimulates the transcription of the insulin receptor
      gene.
AB  - Our previous studies proved that berberine (BBR) up-regulates the insulin
      receptor (InsR) gene by stimulating its promoter and calphostin C blocks this
      effect. Here, the present study was designed to discover the specific kinase
      isoform(s) used by berberine. In the blocking experiment, we found that Go6976, a
      kinase inhibitor that potently inhibit PKCMU/protein kinase D 1 (PKD1),
      effectively and specifically reduced the activity of BBR on InsR. PKD1/PKCMU is a
      member of the PKD family that also covers PKD2 and PKD3/PKCnu with high homology.
      The role of PKD1 in InsR expression was also proved by using another PKD
      activator oligomycin. In the RNA interference experiment, we found that the
      effects of BBR on InsR expression and on cellular glucose consumption were
      partially eliminated by silencing any one of the three PKDs and were totally
      abolished by silencing all of them. BBR enhanced the PKD1 catalytic activity, but
      not its expression. Along with BBR treatment, PKD1 ser916 autophosphorylation was
      increased time- and dose-dependently, indicating an activation of PKD1 by BBR.
      BBR also induces PKD1 translocation from cytosol-to-plasma membrane, further
      verifying the activation of PKD1. These results suggest that the PKD family is
      involved in the transcriptional regulation of the InsR gene; we consider it to be
      a potential new target to discover drugs for sugar-related disorders in the
      future.

PMID- 20674667
TI  - Alternative G protein coupling and biased agonism: new insights into melanocortin
      4 receptor signalling.
AB  - The melanocortin-4 receptor (MC4R) is a prototypical G protein-coupled receptor
      (GPCR) that plays a considerable role in controlling appetite and energy
      homeostasis. Signalling initiated by MC4R is orchestrated by multiple agonists,
      inverse agonism and by interactions with accessory proteins. The exact molecular
      events translating MC4R signalling into its physiological role, however, are not
      fully understood. This review is an attempt to summarize new aspects of MC4R
      signalling in the context of its recently discovered alternative G protein
      coupling, and to give a perspective on how future research could improve our
      knowledge about the intertwining molecular mechanisms that are responsible for
      the regulation of energy homeostasis by the melanocortin system.

PMID- 20674670
TI  - Knockdown of FoxO3a induces increased neuronal apoptosis during embryonic
      development in zebrafish.
AB  - Neuronal apoptosis sculpts the developing brain, and nearly all identified
      classes of neurons seem to be produced "in excess" during development. FoxO
      transcription factors regulate apoptosis in vitro in deprived of neurotrophins.
      It is unknown if FoxO3a is involved in the development of neurons. Here, we
      report a role of FoxO3a during neuronal development in zebrafish. By using in
      situ hybridization, we revealed that FoxO3a transcripts in zebrafish were
      gradually confined to regions of the central nervous system during embryonic
      development, including the forebrain, midbrain, midbrain-hindbrain boundary and
      hindbrain. By using FoxO3a morpholino antisense oligonucleotides, we observed
      that FoxO3a loss-of-function led to neural developmental defects, including
      increased neural apoptosis as detected by acridine orange and terminal
      deoxynucleotidyl transferase biotin-dUTP nick end labeling. These defects could
      be partially rescued by the injection of FoxO3a mRNA. In this study, we found
      that FoxO3a loss-of-function resulted in the decreased expression of neuronal
      markers as determined by in situ hybridization and relative quantitative real
      time PCR. Furthermore, the activation of FoxO3a was required for the maintenance
      of neuron survival but not necessary for the induction of neurogenesis. Our
      results indicated that FoxO3a might be essential for the maintenance of neural
      development in zebrafish. Therefore, this work provides novel evidence of FoxO3a
      in the embryonic neurodevelopment from zebrafish to other mammals.

PMID- 20674669
TI  - A comparison of patient characteristics and outcomes in selected European and
      U.S. rheumatoid arthritis registries.
AB  - PURPOSE: Randomized controlled trials (RCTs) have demonstrated the efficacy of
      biologic agents in the treatment of rheumatic diseases. However, results from
      RCTs may not be generalizable to clinical practice because of their strict
      inclusion and exclusion criteria. Assessment of safety using RCT data also is
      limited by short duration of follow-up and relatively small sample sizes, which
      generally preclude analysis of longer term outcomes and rare adverse events. In
      rheumatology, various observational cohorts and registries have been created to
      complement information obtained from RCTs, some with the primary purpose of
      monitoring effectiveness and safety of biologic agents. Most registries are
      either drug based or disease based. These registries include patients with a
      variety of rheumatic diseases including RA. METHODS: To provide a qualitative
      comparison of selected U.S. and European rheumatoid arthritis (RA) biologics
      registries and cohorts including ARTIS, BIOBADASER, BSRBR, BRASS, CLEAR, CORRONA,
      NDB, RABBIT, SCQM, and VARA. RESULTS: A careful comparison of these registries,
      as provided in this article, can provide a basis for understanding the many
      similarities and differences inherent in their design, as well as societal
      context and content, all of which can significantly impact their results and
      comparisons across registers. SUMMARY: The increasing use of biologic agents for
      treatment of rheumatic diseases has raised important questions about cost,
      safety, and effectiveness of these agents. The unique and variable features of
      patient populations and registry designs in Europe and the U.S. provide valuable
      and complementary data on comparative effectiveness and safety of biologic agents
      to what can be derived from RCTs.

PMID- 20674671
TI  - Effect of osmolarity on CSF volume during ventriculo-aqueductal and ventriculo
      cisternal perfusions in cats.
AB  - The effect of cerebrospinal fluid (CSF) osmolarity on the CSF volume has been
      studied on different CSF/brain tissue contact areas. It has been shown, on
      anesthetized cats under normal CSF pressure, that the perfusion of CSF system
      (12.96 MUl/min) by hyperosmolar CSF (400 mOsml/l) leads to significantly higher
      outflow volume (MUl/min) during ventriculo-cisternal perfusion (29.36 +/- 1.17
      and 33.50 +/- 2.78) than the ventriculo-aqueductal perfusion (19.58 +/- 1.57 and
      22.10 +/- 2.31) in experimental period of 30 or 60 min. Both of these
      hyperosmolar perfusions resulted in significantly higher outflow volume than the
      perfusions by isoosmolar artificial CSF (12.86 +/- 0.96 and 13.58 +/- 1.64).
      These results suggest that the volume of the CSF depends on both the CSF
      osmolarity and the size of the contact area between CSF system and surrounding
      tissue exposed to hyperosmolar CSF. However, all of these facts imply that the
      control of the CSF volume is not in accordance with the classical hypothesis of
      cerebrospinal fluid hydrodynamic. According to this hypothesis, the CSF volume
      should be regulated by active formation of CSF (secretion) inside the brain
      ventricles and passive CSF absorption outside of the brain. Obtained results
      correspond to the new hypothesis which claims that the volume of CSF depends on
      the gradients of hydrostatic and osmotic forces between the blood on one side and
      extracellular fluid and CSF on the other. The CSF exchange between the entire CSF
      system and the surrounding tissue should, therefore, be determined by
      (patho)physiological conditions that predominate within those compartments.

PMID- 20674672
TI  - A putative role for hypothalamic glucocorticoid receptors in hypertension induced
      by prenatal undernutrition in the rat.
AB  - Prenatal undernutrition induces hypertension later in life, possibly by
      disturbing the hypothalamo-pituitary-adrenal axis through programming decreased
      expression of hypothalamic glucocorticoid receptors. We examined the systolic
      blood pressure, heart rate and plasma corticosterone response to intra
      paraventricular dexamethasone, mifepristone and corticosterone in eutrophic and
      prenatally undernourished young rats. Undernutrition was induced during fetal
      life by restricting the diet of pregnant mothers to 10 g daily (40% of diet
      consumed by well-nourished controls). At day 40 of postnatal life (i) intra
      paraventricular administration of dexamethasone significantly reduced at least
      for 24h both the systolic pressure (-11.6%), the heart rate (-20.8%) and the
      plasma corticosterone (-40.0%) in normal animals, while producing lower effects (
      5.5, -8.7, and -22.3%, respectively) on undernourished rats; (ii) intra
      paraventricular administration of the antiglucocorticoid receptor ligand
      mifepristone to normal rats produced opposite effects (8.2, 20.3, and 48.0%
      increase, respectively) to those induced by dexamethasone, being these not
      significant in undernourished animals; (iii) intra-paraventricular corticosterone
      did not exert any significant effect. Results suggest that the low sensitivity of
      paraventricular neurons to glucocorticoid receptor ligands observed in prenatally
      undernourished rats could be due to the already reported glucocorticoid receptor
      expression, found in the hypothalamus of undernourished animals.

PMID- 20674673
TI  - GluR2/3 label expression of the AMPA-type glutamate receptor in the hippocampal
      formation of the homing pigeon stabilizes just after birth.
AB  - The compositions of the glutamate AMPA-type receptors influence the neural
      response and the subunits GluR2/3 has been referred to as essential for receptor
      trafficking and synapse consolidation. We investigate the GluR2/3 occurrence and
      expression in the hippocampal formation of newly born homing pigeons by a semi
      quantitative approach, the Western-blotting technique and by
      immunohistochemistry. Immunoreactivity for GluR2/3 occurs before hatching has
      been evident in neuropil that was fully dispersed over the hippocampus proper
      (HP) and the area parahippocampalis (APH). Although many HP cells are NeuN
      positives, a specific neuronal protein indicating that they are already
      differentiated as neurons while not one contains GluR2/3 at the hatching day
      (P0). Few neurons at the APH seem to express GluR2/3 at P0, but 3 days later (P3)
      the GluR2/3 labeling can be recognized in many HP neurons, showing a distribution
      pattern that resembles the adult, gradually increasing in intensity until P10.
      Also, the Western-blot shows an augment between P0 and P3, remaining stable after
      that. The enhancement of the neuronal label at P3 coincides with the retraction
      of the GluR2/3 label in neuropil, reducing their occurrence during the
      maturational period to become restricted to the dorsomedial portion as reported
      for adults. As the HP GluR2/3-containing cells are supposedly projecting neurons,
      taking together, the results signalize the relevance of the GluR2/3 in post-hatch
      formation of avian hippocampal circuitry in which the third day seems to be the
      critical period.

PMID- 20674674
TI  - Influence of methylprednisolone on magnetic resonance and histological measures
      during cuprizone-induced demyelination.
AB  - MRI is widely used for routine assessment of the progression of white matter
      injury while patients receive therapeutic agents, such as the glucocorticoid
      agonist methylprednisolone (MP). Given this, it is important to determine whether
      MRI parameters are altered by MP treatment in the absence of changes in cellular
      and myelin pathology. In this study, we compared magnetic resonance and
      histological measures during myelin injury in mice with and without short
      duration MP administration. Mice were scanned with a 4.7T MRI scanner before and
      after MP or vehicle injections using T2WI and DTI sequences and histology was
      performed on the brains following the second scan. Comparison of post-injection
      to pre-injection MRI showed a reduced T2WI intensity in the CC and an attenuated
      response in ADC|| and ADC perpendicular in the MP group in comparison with the
      vehicle group. However, quantitative analyses of myelin staining, neurofilament
      intensity and oligodendrocyte and microglial density were not different between
      the MP and the vehicle groups, indicating that the short duration MP treatment
      did not alter cellular and myelin pathology. These data suggest that MP could
      confound the validity of paraclinical measures such as ADC|| and ADC
      perpendicular that are otherwise being touted as markers of either axonal
      integrity or myelin repair.

PMID- 20674675
TI  - APP, APOE, complement receptor 1, clusterin and PICALM and their involvement in
      the herpes simplex life cycle.
AB  - The major Alzheimer's disease susceptibility genes (APOE, clusterin, complement
      receptor 1 (CR1) and phosphatidylinositol binding clathrin assembly protein,
      PICALM) can be implicated directly (APOE, CR1) or indirectly (clusterin and
      PICALM) in the herpes simplex life cycle. The virus binds to proteoliposomes
      containing APOE or APOA1 and also to CR1, and both clusterin and PICALM are
      related to a mannose-6-phosphate receptor used by the virus for cellular entry
      and intracellular transport. PICALM also binds to a nuclear exportin used by the
      virus for nuclear egress. Clusterin and complement receptor 1 are both related to
      the complement pathways and play a general role in pathogen defence. In addition,
      the amyloid precursor protein APP is involved in herpes viral transport and gamma
      secretase cleaves a number of receptors used by the virus for cellular entry.
      APOE, APOA1 and clusterin, or alpha 2-macroglobulin, insulysin and caspase 3,
      which also bind to the virus, are involved in beta-amyloid clearance or
      degradation, as are the viral binding complement components, C3 and CR1. There
      are multiple ways in which the products of key susceptibility genes might be able
      to modify the viral life cycle and in turn the virus interacts with key proteins
      involved in APP and beta-amyloid processing. These interactions support a role
      for the herpes simplex virus in Alzheimer's disease pathology and suggest that
      antiviral agents or vaccination might be considered as viable therapeutic
      strategies in Alzheimer's disease.

PMID- 20674676
TI  - Protective effect of (-)clausenamide against Abeta-induced neurotoxicity in
      differentiated PC12 cells.
AB  - The neurotoxicity of aggregated beta-amyloid (Abeta) has been implicated as a
      critical cause in the pathogenesis of Alzheimer's disease (AD). In the present
      study, we investigated the effect of (-)clausenamide ((-)Clau), an aqueous
      extract of leaves of Clausena lassium (lour) skeel, on the neurotoxicity of
      Abeta(25-35). The viability of differentiated PC12 cells was determined by MTT
      assay. Apoptosis was detected by flow cytometry. DCFH-DA was used for assessment
      of intracellular ROS generation, JC-1 and Rhodamine 123 for measurement of
      mitochondrial transmembrane potential (MMP). The intracellular calcium was
      determined with Fluo-3. The phosphorylation of p38 MAPK and the expression of Bcl
      2, Bax, P53, Caspase 3 were examined by Western blot. The results showed that (
      )Clau significantly elevated cell viability. Furthermore, (-)Clau arrested the
      apoptotic cascade by reversing overload of calcium, preventing ROS generation,
      moderated the dissipation of MMP and the misbalance of Bcl-2 and Bax, inhibiting
      the activation of p38 MAPK and the expression of P53 and cleaved Caspase 3. Our
      results suggested that (-)Clau may be a therapeutic agent for AD.

PMID- 20674677
TI  - Dissociation of summation and peak latencies in visual processing: an MEG study
      on stimulus eccentricity.
AB  - Research on the temporal characteristics of visual processing, as measured with
      critical flicker fusion or the latency of visual evoked potential (VEP), shows
      controversial results if different eccentricities of visual stimuli are compared.
      To clarify this question, a direct measure of cortical activity with
      magnetoencephalography (MEG) was applied to examine the neuronal summation
      latency and peak latency for both near and far peripheral stimuli. Consistent
      with cortical magnification, the peak amplitude for less eccentric stimuli was
      larger than that for more eccentric stimuli. More importantly, the current data
      also demonstrated longer cortical summation latency and peak latency for more
      eccentric visual stimuli, but only the summation latency difference between near
      and far stimuli correlated with the peak amplitude difference between near and
      far stimuli. These results suggest dissociable mechanisms of summation latency
      and peak latency with respect to their contributions to the stimulus eccentricity
      effect, and provide potential explanations for controversial results in previous
      studies.

PMID- 20674678
TI  - Improvements in proprioceptive functioning influence multisensory-motor
      integration in 7- to 13-year-old children.
AB  - Accurate and efficient sensorimotor behavior depends on precise localization of
      the body in space, which may be estimated using multiple sensory modalities
      (i.e., vision and proprioception). Although age-related differences in
      multisensory-motor integration across childhood have been previously reported,
      the extent to which age-related changes in unimodal functioning affect
      multisensory-motor integration is unclear. The purpose of the current study was
      to address this knowledge gap. Thirty-seven 7- to 13-year-old children moved
      their dominant hand in a target localization task to visual, proprioceptive, and
      concurrent visual and proprioceptive stimuli. During a subsequent experimental
      phase, we introduced a perturbation that placed the concurrent visual and
      proprioceptive stimuli in conflicting locations (incongruent condition) to
      determine the relative contributions of vision and proprioception to the
      multisensory estimate of target position. Results revealed age-related
      differences in the localization of incongruent stimuli in which the visual
      estimate of target position contributed more to the multisensory estimate in the
      younger children whereas the proprioceptive estimate was up-weighted in the older
      children. Moreover, above and beyond the effects of age, differences in
      proprioceptive functioning systematically influenced the relative contributions
      of vision and proprioception to the multisensory estimate during the incongruent
      trials. Specifically, improvements in proprioceptive functioning resulted in an
      up-weighting of proprioception, suggesting that the central nervous system of
      school-aged children utilizes information about unimodal functioning to integrate
      redundant sensorimotor inputs.

PMID- 20674679
TI  - Spatial short-term memory in rats: effects of learning trials on metabolic
      activity of limbic structures.
AB  - The oxidative metabolism was assessed in the hippocampus and related regions in
      rats that were trained in a spatial short-term memory task in the water maze
      following distinct training schedules. The cytochrome oxidase (COx)
      histochemistry was evaluated in groups of rats that received a daily session made
      up of either two or three learning trials. An untreated group was added to
      determine baseline levels of COx. We found that the 3-Trials group exhibited a
      better performance concerning the differences in latency between trials 1 and 2.
      Trained groups showed higher COx activity than the untreated group in the medial
      prefrontal cortex, dentate gyrus, CA1, and the mammillary region. However, a
      decrease in COx activity was found in the dentate gyrus, CA1, and supramammillary
      region of the 3-Trials group. In addition, COx activity levels found in this
      group were similar to those of the untreated group in some thalamic nuclei. Most
      of the regions that presented significant correlations between COx activity and
      behavioral scores were found in the 3-Trials group. These findings suggest an
      influence of task difficulty in the oxidative metabolism of brain regions
      involved in spatial learning.

PMID- 20674680
TI  - Localization and trafficking of endogenous anterior pharynx-defective 1, a
      component of Alzheimer's disease related gamma-secretase.
AB  - Anterior pharynx-defective 1 (Aph-1) is a multi-spanning membrane protein and an
      integral component of the high molecular weight gamma-secretase complex that also
      contains presenilin, nicastrin, and Pen-2. In order to clarify the existence of
      an endogenous fragment of Aph-1 and dissect the localization and processing of
      endogenous Aph-1 proteins, we examined cell lines and primary cell cultures with
      our own carboxyl terminal-specific antibodies for Aph-1aL. Fractionation and
      immunofluorescence studies indicated that the endogenous full-length Aph-1aL
      isoform localizes primarily to the endoplasmic reticulum as well as Golgi
      intermediate compartment, but small amount of it was detected at Golgi apparatus
      where most of its carboxyl terminal domain fragment existed. In primary neuronal
      and glial cultures, Aph-1aL was present in the neurites and glial cell processes.
      Endogenous Aph-1a and its proteolytic fragment have unique properties for
      cleavage control that may have implications for gamma-secretase regulation and
      intracellular distribution.

PMID- 20674682
TI  - The circling ci2 rat mutant revisited: receptor architecture of the motor cortex.
AB  - Circling behaviour of the ci2 rat mutant has been associated with an abnormal
      laterality concerning nigrostriatal and vestibular dopamine content and densities
      of several neurotransmitter receptors. Since not only subcortical, but also
      cortical activity subserve behavioural asymmetry, we applied quantitative in
      vitro receptor autoradiography to determine the densities of twenty
      neurotransmitter receptors in three areas of the motor cortex (Fr1, Fr2, Fr3) of
      the left and right hemispheres in adult male circling mutant rats (ci2/ci2), non
      circling littermates (ci2/+) and aged-matched rats from the background strain
      (LEW/Ztm, wild type). Rats had previously been monitored for motor behaviour and
      swimming abilities. Wild type and ci2/+ rats did not differ from the behavioural
      point of view, whereas ci2/ci2 animals were characterized by pronounced
      lateralized circling behaviour and were not able to perform the swimming test
      correctly. Left Fr2 of wild type rats contained significantly lower NMDA receptor
      densities than its right counterpart. No interhemispheric differences were found
      in the motor cortex of ci2/+ or ci2/ci2 animals. All three areas of wild type
      rats contain higher GABA(A) and adenosine A(1) receptor densities than those of
      ci2/+ and ci2/ci2 animals, respectively. Serotonin 5-HT(2) receptor densities
      were significantly lower in the motor cortex of ci2/ci2 animals than in that of
      their heterozygous littermates. Thus, since the ci2 rat mutant presents a wide
      range of behavioural and neurochemical lateralization anomalies, in addition to
      representing a model of Usher syndrome type 1, it may prove useful to understand
      the mechanisms underlying abnormal rotational behaviour and its relevance as a
      model of disturbances in cerebral asymmetry and their consequences.

PMID- 20674683
TI  - A transgenic mouse model of neuroepithelial cell specific inducible
      overexpression of dopamine D1-receptor.
AB  - Dopamine and its receptors appear in the brain during early embryonic period
      suggesting a role for dopamine in brain development. In fact, dopamine receptor
      imbalance resulting from impaired physiological balance between D1- and D2
      receptor activities can perturb brain development and lead to persisting changes
      in brain structure and function. Dopamine receptor imbalance can be produced
      experimentally using pharmacological or genetic methods. Pharmacological methods
      tend to activate or antagonize the receptors in all cell types. In the
      traditional gene knockout models the receptor imbalance occurs during development
      and also at maturity. Therefore, assaying the effects of dopamine imbalance on
      specific cell types (e.g. precursor versus postmitotic cells) or at specific
      periods of brain development (e.g. pre- or postnatal periods) is not feasible in
      these models. We describe a novel transgenic mouse model based on the
      tetracycline dependent inducible gene expression system in which dopamine D1
      receptor transgene expression is induced selectively in neuroepithelial cells of
      the embryonic brain at experimenter-chosen intervals of brain development. In
      this model, doxycycline-induced expression of the transgene causes significant
      overexpression of the D1-receptor and significant reductions in the incorporation
      of the S-phase marker bromodeoxyuridine into neuroepithelial cells of the basal
      and dorsal telencephalon indicating marked effects on telencephalic neurogenesis.
      The D1-receptor overexpression occurs at higher levels in the medial ganglionic
      eminence (MGE) than the lateral ganglionic eminence (LGE) or cerebral wall (CW).
      Moreover, although the transgene is induced selectively in the neuroepithelium,
      D1-receptor protein overexpression appears to persist in postmitotic cells. The
      mouse model can be modified for neuroepithelial cell-specific inducible
      expression of other transgenes or induction of the D1-receptor transgene in other
      cells in specific brain regions by crossbreeding the mice with transgenic mouse
      lines available already.

PMID- 20674684
TI  - The protective effects of interleukin-18 and interferon-gamma on neuronal damages
      in the rat hippocampus following status epilepticus.
AB  - To elucidate whether interleukin-18 (IL-18) or interferon-gamma (IFN-gamma)
      participates in neurodegeneartion, we investigated the changes in IL-18 and IFN
      gamma systems within the rat hippocampus following status epilepticus (SE). In
      non-SE induced animals, IL-18, IL-18 receptor alpha (IL-18Ralpha), IFN-gamma and
      IFN-gamma receptor alpha (IFN-gammaRalpha) immunoreactivity was not detected in
      the hippocampus. Following SE, IL-18 immunoreactivity was increased in CA1-3
      pyramidal cells as well as dentate granule cells. IL-18 immunoreactivity was also
      up-regulated in astrocytes and microglia/macrophages. IL-18Ralpha
      immunoreactivity was detected in astrocytes and microglia/macrophages. IFN-gamma
      immunoreactivity was detected only in astrocytes within all regions of the
      hippocampus. IFN-gammaRalpha immunoreactivity was increased in neurons as well as
      astrocytes. Intracerebroventricular infusions of recombinant rat IL-18 or IFN
      gamma alleviated SE-induced neuronal damages, while neutralization of IL-18, IFN
      gamma or their receptors aggravated them, as compared to saline-infused animals.
      These findings suggest that astroglial-mediated IFN-gamma pathway in response to
      IL-18 induction may play an important role in alleviation of SE-induced neuronal
      damages.

PMID- 20674685
TI  - Effect of transition metals in synaptic damage induced by amyloid beta peptide.
AB  - The amyloid beta-peptide (Abeta), which is thought to be the major cause of
      Alzheimer's disease (AD), is known to be capable of aggregating in different
      states: soluble monomers and oligomers, and insoluble aggregates. The Abeta
      aggregation state as well as its toxicity has been related to the interaction
      between the peptide and transition metals such as iron and copper. However, this
      relationship, as well as the effects of Abeta on the synaptic endings, is not
      fully understood. The aggregation states of Abeta in the presence of iron and
      copper, as well as their effects on synaptic viability and signaling were
      investigated in this work. During acute incubation treatments (5 min-4 h),
      Abeta/metal impaired mitochondrial function to the same extent as has been
      observed with the metal alone. However, in the presence of Abeta/iron (10 and 50
      muM), plasma membrane integrity was disrupted to a greater extent than when
      generated by either iron or Abeta alone, indicating that the membrane constitutes
      the first target of synaptic injury. Akt activation by Abeta/iron was evident
      after 5 min of incubation and was higher than that observed in the presence of
      the metal alone. This activation was barely detected after 4 h of incubation,
      demonstrating that there is no correlation between the extent of synaptic damage
      and the activation of this kinase. Extracellular signal-regulated kinases 1 and 2
      (ERK1/2) activation profile was different from that observed for Akt.
      Accordingly, the presence of Abeta/metal could differentially modulate the
      activity of these kinases. This work shows evidence of the initial events locally
      triggered at the synapse by Abeta and transition metals. As synapses have been
      proposed as the starting point of Abeta/metal-triggered events, the
      characterization of early mechanisms occurring in models that mimic AD could be
      important for the search of unexplored therapeutics tools.

PMID- 20674686
TI  - Neuropeptide coding of sympathetic preganglionic neurons; focus on adrenally
      projecting populations.
AB  - Chemical coding of sympathetic preganglionic neurons (SPN) suggests that the
      chemical content of subpopulations of SPN can define their function. Since
      neuropeptides, once synthesized are transported to the axon terminal, most
      demonstrated chemical coding has been identified using immunoreactive terminals
      at the target organ. Here, we use a different approach to identify and quantify
      the subpopulations of SPN that contain the mRNA for pituitary adenylate cyclase
      activating polypeptide (PACAP) or enkephalin. Using double-labeled
      immunohistochemistry combined with in situ hybridization (ISH) we firstly
      identified the distribution of these mRNAs in the spinal cord and determined
      quantitatively, in Sprague-Dawley rats, that many SPN at the T4-T10 spinal level
      contain preproPACAP (PPP+, 80 +/- 3%, n=3), whereas a very small percentage
      contain preproenkephalin (PPE+, 4 +/- 2%, n=4). A similar neurochemical
      distribution was found at C8-T3 spinal level. These data suggest that PACAP
      potentially regulates a large number of functions dictated by SPN whereas
      enkephalins are involved in few functions. We extended the study to explore those
      SPN that control adrenal chromaffin cells. We found 97 +/- 5% of adrenally
      projecting SPN (AP-SPN) to be PPP+ (n=4) with only 47 +/- 3% that were PPE+
      (n=5). These data indicate that adrenally projecting PACAPergic SPN regulate both
      adrenal adrenaline (Ad) and noradrenaline (NAd) release whereas the
      enkephalinergic SPN subpopulation must control a (sub) population of chromaffin
      cells - most likely those that release Ad. The sensory innervation of the adrenal
      gland was also determined. Of the few adrenally projecting dorsal root ganglia
      (AP-DRG) observed, 74 +/- 12% were PPP+ (n=3), whereas 1 +/- 1% were PPE+ (n=3).
      Therefore, if sensory neurons release peptides to the adrenal medulla, PACAP is
      most likely involved. Together, these data provide a neurochemical basis for
      differential control of sympathetic outflow particularly that to the adrenal
      medulla.

PMID- 20674687
TI  - The effect of mechanical strain or hypoxia on cell death in subpopulations of rat
      dorsal root ganglion neurons in vitro.
AB  - Spinal nerves and their associated dorsal root ganglion (DRG) cells can be
      subject to mechanical deformation and hypoxia associated with pathology such as
      disc herniation, spinal stenosis and spine trauma. There is very limited
      information on the response of adult DRG neurons to such stressors. In this study
      we used an in vitro approach to examine the response of adult DRG cells to (a)
      mechanical, hypoxic, and combined injuries; and (b) to compare the effects on
      injury on nociceptive and non-nociceptive neurons, as well as on non-neuronal
      cells. Mechanical injury (20% tensile strain) led to significant neuronal cell
      death (assessed by ethidium homodimer-1 labelling), which was proportional to
      strain duration (5 min, 1 h, 6 h or 18 h). Hypoxia (2% O(2) for 24 h) also
      promoted death of DRG neurons, and was further enhanced when mechanical strain
      and hypoxia were combined. Both mechanical strain and hypoxia significantly
      decreased the maximum neurite length. Conversely, death of non-neuronal cells was
      only increased by hypoxia and not by mechanical strain. Total cell death in
      response to mechanical injury or hypoxia was similar in both non-nociceptive
      (neurofilament, NF-200 immunoreactive) and nociceptive (calcitonin gene-related
      peptide, CGRP immunoreactive) neurons, but apoptosis (assessed by activated
      caspase-3 immunostaining) was significantly higher in CGRP than NF-200 neurons.
      Surprisingly, cell death of non-peptidergic nociceptors (identified by Griffonia
      simplicifolia IB4 lectin binding) was already high in control cultures, and was
      not increased further by either mechanical stretch or hypoxia. These results
      provide detailed information on the response of adult DRG subpopulations to
      hypoxia and mechanical strain, and describe in vitro models that could be useful
      for screening potential neuroprotective agents.

PMID- 20674688
TI  - Penile and urethral cancers are not common entities. Preface.

PMID- 20674689
TI  - Anatomic considerations of the penis, lymphatic drainage, and biopsy of the
      sentinel node.
AB  - This article reviews anatomic considerations in penile and urethral surgery, with
      a particular emphasis on lymphatic anatomy. The historical evolution of
      techniques to reduce the unnecessary use and operative morbidity of
      inguinofemoral lymph node dissection are reviewed, with an emphasis on sentinel
      node (SN) biopsy and dynamic SN biopsy techniques.

PMID- 20674690
TI  - Penile intraepithelial neoplasia and other premalignant lesions of the penis.
AB  - Invasive penile cancer is an aggressive malignancy that often requires partial or
      complete penile amputation. Premalignant penile lesions, such as penile
      intraepithelial neoplasia, will have been present prior to the development of
      invasive disease in a substantial percentage of patients. Early detection and
      treatment of premalignant penile lesions may prevent malignant progression while
      avoiding penile amputation. This review focuses on premalignant penile lesions
      and the associations of these lesions with the development of invasive penile
      cancer.

PMID- 20674691
TI  - Penile cancer: clinical presentation, diagnosis, and staging.
AB  - Penile cancer is an uncommon malignancy in developed countries, with an estimated
      1290 new cases of invasive penile cancer and 290 deaths among men in the United
      States in 2009, but is much more common in the developing countries of Asia,
      Africa, and South America. This disease can result in loss of function,
      disfigurement, and death. Thus, recognizing penile cancer early in the clinical
      setting and accurately diagnosing the patients is critical. Because the
      management and prognosis varies by the extent of local disease, lymph node
      status, and other factors, accurate staging of penile cancer is of utmost
      importance. This article focuses on the presentation, diagnosis, and staging of
      invasive squamous cell carcinoma of the penis. The authors highlight the recent
      changes to the American Joint Committee on Cancer's staging system for penile
      carcinoma and discuss other prognostic factors and predictive models.

PMID- 20674692
TI  - Imaging tumors of the penis and urethra.
AB  - In penile and urethral cancers, imaging has come to play a crucial role in
      enhancing the precision of clinical staging and facilitating optimal surgical
      planning. Over the years, great improvements have occurred in imaging. High
      resolution magnetic resonance imaging (MRI) now represents the gold standard for
      evaluating the primary tumor and its local extension. Lymphotropic nanoparticle
      enhanced MRI, dynamic sentinel lymph node biopsy, and ultrasonography with fine
      needle aspiration seem to be the superior modalities for detecting malignant
      regional lymph nodes. Positron emission tomography combined with computed
      tomography has shown great promise as a whole body screen for the detection of
      distant metastases. Ultimately, the ability of imaging to augment clinical
      evaluation and enhance the accuracy of staging penile and urethral cancers will
      translate into improved surgical decision making and overall superior patient
      outcomes.

PMID- 20674693
TI  - Surgical management of carcinoma of the penis.
AB  - The potential devastating impact of curative traditional surgery on the patient's
      quality of life should always be a consideration even as urologic oncologists
      attempt to cure this potentially life-threatening malignancy. The development of
      penile-preserving surgical techniques will reduce the negative impact of
      amputations on functional and cosmetic outcomes only if oncologists continue to
      place oncologic objectives first and foremost for patients.

PMID- 20674694
TI  - Reconstruction of the penis after surgery.
AB  - This article describes penile reconstruction after surgery. Patient
      considerations in reconstruction, reconstruction of varied urethral defects,
      general principles of urethroplasty, surgical techniques of urethral
      reconstruction, reconstruction of scrotal and testicular defects, reconstruction
      of the penile shaft, and timing of reconstruction are discussed. The use of local
      pedicled flaps in penile reconstruction, distant free tissue transfer in penile
      reconstruction, varied forms of prostheses, management of complications following
      penile reconstruction, postoperative care in penile reconstruction patient, and
      penile transplantation are described.

PMID- 20674695
TI  - Mohs micrographic surgery for penoscrotal malignancy.
AB  - Mohs micrographic surgery (MMS) has been shown to reduce recurrence rates when
      used to excise many different mucocutaneous neoplasms, especially of the head and
      neck. The low recurrence rates are due to careful microscopic evaluation of the
      horizontal and vertical surgical margins. This article discusses the utility and
      limitations of MMS in controlling neoplasia of the male genitalia. Specific
      penoscrotal neoplasias discussed in this article include invasive and in situ
      squamous cell carcinoma, basal cell carcinoma, extramammary Paget disease, and
      granular cell tumor.

PMID- 20674696
TI  - Penile cancer: management of regional lymphatic drainage.
AB  - Presence and magnitude of the inguinal nodal metastases are the most important
      determinants of oncologic outcome in patients with squamous carcinoma of the
      penis (SCP). Surgical removal of the inguinal lymph nodes provides an important
      staging and therapeutic benefit to SCP patients, while the methodology of
      appropriate patient selection for lymph node dissection continues to evolve.
      Compliant, motivated, and reliable patients with low risk of harboring metastatic
      inguinal lymph nodes can be managed with careful inguinal surveillance. In SCP
      patients whose primary tumors demonstrate pathologic features of aggressive
      disease, modified bilateral inguinal lymph node dissection should be performed
      and converted to classic ilioinguinal lymph node dissection if metastatic disease
      is confirmed on frozen sections. Patients with bulky inguinal metastases are
      unlikely to be cured by surgery alone. Integration of systemic therapy,
      especially in a presurgical setting, is an attractive strategy for management of
      patients with advanced SCP, and is currently being studied prospectively.

PMID- 20674697
TI  - Controversies in ilioinguinal lymphadenectomy.
AB  - Patients with penile cancer who are proven to have negative inguinal lymph nodes
      have an excellent prognosis. Furthermore, patients with small-volume inguinal
      node involvement can often be cured by surgery alone. Lymphadenectomy has clear
      survival benefits for patients when applied to those with lymph node metastasis.
      However, the current morbidity of the standard technique of lymphadenectomy is an
      impediment to its universal application, and innovative strategies to reduce the
      morbidity of staging/treatment that do not compromise oncologic control must be
      developed and standardized. The optimal integration of multimodality therapy to
      improve survival in advanced disease will occur only through collaborative
      studies between centers with significant patient volume, which would be
      facilitated through the development of regional referral centers.

PMID- 20674698
TI  - Radiation therapy for cancer of the penis.
AB  - Radiotherapy, in the form of external beam radiotherapy or interstitial
      brachytherapy, provides an effective penile-sparing option for localized squamous
      cell carcinoma of the penis. Interstitial brachytherapy is completed in 4 to 5
      days and provides 5-year penile preservation rates of 70% to 88%, and at 10
      years, 67% to 72%. Surgery provides effective salvage for local failures,
      maintaining cause-specific survival at 84% to 92% at 10 years. Ideal tumors for
      brachytherapy should be less than 4 cm without extension onto the shaft. More
      advanced cases can be considered for external radiotherapy.

PMID- 20674699
TI  - Surgery for urethral cancer.
AB  - Primary urethral cancers represent less than 1% of genitourinary malignancy.
      Given this is an uncommon disease, there are limited data to guide diagnostic and
      treatment strategies. Surgical extirpation remains the standard for most
      patients, with the addition of chemotherapy and radiation therapy in select
      patients. The surgical approach to urethral cancer depends largely on the
      location and extent of the tumor.

PMID- 20674700
TI  - Carcinoma of the urethra: radiation oncology.
AB  - Urethral cancer is a rare but aggressive neoplasm. Early-stage distal lesions can
      be successfully treated with a single modality. Results for definitive
      radiotherapy using either or both external beam radiation therapy and
      brachytherapy have shown excellent cure rates in men and women. The primary
      advantage of radiotherapy is organ preservation. Advanced tumors, however, have
      poor outcomes with single modality treatment. Results have been improved using a
      combination of radiotherapy and chemotherapy, chiefly 5-fluorouracil and
      mitomycin C. Although literature is limited to case reports because of the rarity
      of the disease, the markedly improved results compared with older results of
      surgery with or without radiation warrant consideration.

PMID- 20674701
TI  - Chemotherapy for penile and urethral carcinoma.
AB  - Although surgery is the mainstay of curative treatment of carcinomas of the penis
      and urethra, there is a role for systemic cytotoxic chemotherapy for locally
      advanced, unresectable, or metastatic tumors. Although this field is limited by a
      paucity of clinical trials or prospective data, the available single
      institutional retrospective reviews indicate that multi-agent cisplatin-based
      combination chemotherapy regimens have significant activity and may allow
      curative surgery for patients with otherwise unresectable tumors. Toxicity
      remains a concern in this typically older patient population, and clearly new
      regimens are necessary. This article reviews the available literature on
      chemotherapy for carcinoma of the penis and urethra in the neoadjuvant, adjuvant,
      and metastatic setting.

PMID- 20674702
TI  - Management of the male urethra after cystectomy.
AB  - Approximately 70,000 new cases of bladder cancer are diagnosed yearly, of which
      52,000 are male patients. In 2009 there were approximately 14,000 deaths
      attributed to bladder cancer, 10,000 of which were men. Approximately 40% to 45%
      of all cases are high-grade tumors with half of these being muscle-invasive
      tumors at the time of diagnosis. With the preponderance of men in this
      population, there is a need for clear management strategies regarding the
      retained urethra in those men undergoing radical cystectomy. This article reviews
      the incidence of urothelial carcinoma in the retained urethra, risk factors for
      the development of urethral urothelial carcinoma, surveillance strategies,
      treatment modalities, and outcomes following intervention.

PMID- 20674703
TI  - Homebase behavior of zebrafish in novelty-based paradigms.
AB  - Zebrafish (Danio rerio) are emerging as a promising model species in neuroscience
      research. Many traditional rodent behavioral paradigms may be adapted for
      zebrafish testing. Exposing zebrafish to three different "open field" tanks for
      30 min, we showed that fish display robust homebase behavior, in which one area
      of the tank is chosen as a preferred point of reference during the test, which
      the fish frequently return to and spend a longer duration in. This phenotype
      strikingly resembles rodent homebase behavior, confirming that both species use
      homebases as "reference points" for their exploration. Our study introduces a
      simple method for zebrafish homebase phenotyping, and further supports the
      utility of these fish in neurobehavioral and cognitive research.

PMID- 20674704
TI  - Demand for sucrose in the genetically obese Zucker (fa/fa) rat.
AB  - Obese Zucker rats (fa/fa) eat more food than lean controls in free-feeding
      conditions, which strongly influences their phenotypic expression. Few studies,
      however, characterize their food consumption in environments that are more
      representative of foraging conditions, e.g., how effort plays a role in food
      procurement. This study examined the reinforcing efficacy of sucrose in obese
      Zucker rats by varying the responses required to obtain single sucrose pellets.
      Male Zucker rats (15 lean, 14 obese) lever-pressed under eight fixed ratio (FR)
      schedules of sucrose reinforcement, in which the number of lever-presses required
      to gain access to a single sucrose pellet varied from 1 to 300. Linear and
      exponential demand equations, which characterize the value of a reinforcer by its
      sensitivity to price (FR), were fit to the number of food reinforcers and
      responses made. Free food consumption was also examined. Obese Zuckers, compared
      to leans, consumed more food under free-feeding conditions. Moreover, they had
      higher levels of consumption and response output, but only at low FR values. Both
      groups were equally sensitive to price increases at higher FR values. This
      suggests that environmental conditions may interact with genes in the expression
      of food reinforcer efficacy.

PMID- 20674705
TI  - Home birth--proceed with caution.

PMID- 20674706
TI  - The science and practice of HIV prevention.

PMID- 20674707
TI  - Delays in UK stroke prevention.

PMID- 20674708
TI  - The double-helix derailed: the story of the BRCA patent.

PMID- 20674710
TI  - Jean William Pape: GHESKIO founder and Gates Award winner.

PMID- 20674712
TI  - Carotid artery stenting versus endarterectomy for carotid stenosis.

PMID- 20674713
TI  - Carotid artery stenting versus endarterectomy for carotid stenosis.

PMID- 20674714
TI  - Human papillomavirus vaccine coverage.

PMID- 20674715
TI  - Human papillomavirus vaccine coverage.

PMID- 20674717
TI  - Colorectal cancer.

PMID- 20674718
TI  - Colorectal cancer.

PMID- 20674720
TI  - Clinical Trials Directive: better regulation required now.

PMID- 20674721
TI  - Pneumonia's link with the head and heart.

PMID- 20674722
TI  - Development of multiple W/O/W emulsions as dermal carrier system for
      oligonucleotides: effect of additives on emulsion stability.
AB  - Multiple water-in-oil-in-water (W/O/W) emulsions are of major interest as
      potential skin delivery systems for water-soluble drugs like oligonucleotides due
      to their distinct encapsulation properties. However, multiple emulsions are
      highly sensitive in terms of variations of the individual components. The
      presence of osmotic active ingredients in the inner water phase is crucial for
      the generation of stable multiple emulsions. In order to stabilize the emulsions
      the influence of NaCl, MgSO(4), glucose and glycine and two cellulose derivatives
      was investigated. Briefly, multiple W/O/W emulsions using Span 80 as a lipophilic
      emulsifier and different hydrophilic emulsifiers (PEG-40/50 stearate, steareth-20
      and polysorbate 80) were prepared. Stability of the emulsions was analyzed over a
      period of time using rheological measurements, droplet size observations and
      conductivity analysis. In this study we show that additives strongly influence
      the properties stability of multiple emulsions. By increasing the concentration
      of the osmotic active ingredients, smaller multiple droplets are formed and the
      viscosity is significantly increased. The thickening agents resulted in a
      slightly improved stability. The most promising emulsions were chosen and further
      evaluated for their suitability and compatibility to incorporate a DNAzyme
      oligonucleotide as active pharmaceutical ingredient.

PMID- 20674723
TI  - Reverse micelle-loaded lipid nano-emulsions: new technology for nano
      encapsulation of hydrophilic materials.
AB  - This study presents novel, recently patented technology for encapsulating
      hydrophilic species in lipid nano-emulsions. The method is based on the phase
      inversion temperature method (the so-called PIT method), which follows a low
      energy and solvent-free process. The nano-emulsions formed are stable for months,
      and exhibit droplet sizes ranging from 10 to 200 nm. Hydrophilic model molecules
      of fluorescein sodium salt are encapsulated in the oily core of these nano
      emulsion droplets through their solubilisation in the reverse micellar system. As
      a result, original, multi-scaled nano-objects are generated with a 'hydrophilic
      molecule in a reverse-micelles-in-oil-in-water' structure. Once fluorescein has
      been encapsulated it remains stable, for thermodynamic reasons, and the
      encapsulation yields can reach 90%. The reason why such complex objects can be
      formed is due to the soft method used (PIT method) which allows the conservation
      of the structure of the reverse micelles throughout the formulation process, up
      to their entrapment in the nano-emulsion droplets. In this study, we focus the
      investigation on the process itself, revealing its potential and limits. Since
      the formulation of nanocarriers for the encapsulation of hydrophilic substances
      still remains a challenge, this study may constitute a significant advance in
      this field.

PMID- 20674724
TI  - Determination of partition and binding properties of solutes to stratum corneum.
AB  - The binding property of a number of relatively hydrophilic solutes to native and
      delipidized stratum corneum (SC) and their partition coefficients to extracted
      lipid have been measured by equilibration experiments to expand the current
      database which consisted of mostly hydrophobic solutes. Using the extended
      database, quantitative structure property relationships (QSPR) have been proposed
      for predicting the partition and binding coefficients of both hydrophobic and
      hydrophilic solutes to the SC protein, and lipid. Solute partition to the SC
      lipid is best fitted by PC(lip/w)=K(ow)(0.69) and solute binding to the SC
      protein is best described by PC(pro/w)=4.2K(ow)(0.31). The two QSPR models of
      solute partition to the SC lipid and binding to the SC protein have been further
      combined into a two-phase model to predict the overall partition coefficient of
      solutes to the stratum corneum (K(sc/w)). Our study not only extends the database
      of solute partition and binding properties of the SC to include hydrophilic
      solutes, but also demonstrates that the thermodynamic equilibrium properties of
      the SC partition and binding can be fitted with good accuracy by combining QSPR
      models with the multiphase and heterogeneous structures of the SC.

PMID- 20674725
TI  - Disulfide crosslinked stearoyl carrier peptides containing arginine and histidine
      enhance siRNA uptake and gene silencing.
AB  - The siRNA has been expected to apply for several diseases such as cancer since
      siRNA specifically silences the disease-associated genes. However, effective gene
      carriers should be developed to overcome the low siRNA stability in vivo, form
      stable complexes and facilitate intracellular uptake of siRNA. In this study, to
      develop a safe and efficient siRNA carrier, stearoyl (STR) peptides with Cys (C),
      Arg (R), and His (H) residues that can form disulfide cross linkages via Cys (C)
      were synthesized, and their suitability as siRNA carriers was evaluated. The
      particle size of STR-CH(2)R(4)H(2)C/siRNA complexes was about 100 nm. The
      cellular uptake ability after transfection with FAM-siRNA with STR
      CH(2)R(4)H(2)C, CH(2)R(4)H(2)C, or STR-GH(2)R(4)H(2)G was significantly higher
      than that with FAM-siRNA only. STR-CH(2)R(4)H(2)C showed the highest cellular
      uptake ability when compared with CH(2)R(4)H(2)C and STR-GH(2)R(4)H(2)G. STR
      CH(2)R(4)H(2)C did not induce substantial cytotoxicity. The intratumor injection
      of STR-CH(2)R(4)H(2)C/vascular endothelial growth factor (VEGF) siRNA (siVEGF)
      complexes achieved a high anti-tumor effect in tumor bearing mice. These results
      suggest STR-CH(2)R(4)H(2)C has potential of effective siRNA carrier possible to
      exercise silencing effect in vitro and in vivo.

PMID- 20674726
TI  - The ratio of unsaturated fatty acids in biosurfactants affects the efficiency of
      gene transfection.
AB  - An unsaturated hydrocarbon chain in phospholipid was reported to affect a phase
      transition and a fusogenic activity after mixing membranes, and consequently to
      achieve a high DNA transfection efficiency. We previously showed that a
      biosurfactant mannosylerythritol lipid-A (MEL-A) enhances the gene transfection
      efficiency of cationic liposomes. Here, we have studied the effects of
      unsaturated fatty acid ratio of MEL-A on the physicochemical properties and gene
      delivery into cells of cationic liposomes using MEL-A with three different
      unsaturated fatty acid ratios (9.1%, 21.5%, and 46.3%). The gene transfer
      efficiency of cationic liposomes containing MEL-A (21.5%) was much higher than
      that of those containing MEL-A (9.1%) and MEL-A (46.3%). MEL-A (21.5%)-containing
      cationic liposomes induced highly efficient membrane fusion after addition of
      anionic liposomes and led to subsequent DNA release. Imaging analysis revealed
      that MEL-A (21.5%)-containing liposomes fused with the plasma membrane and
      delivered DNA into the nucleus of NIH-3T3 cells, MEL-A (46.3%)-containing
      liposomes fused with the plasma membrane did not deliver DNA into the nucleus,
      and MEL-A (9.1%)-containing liposomes neither fused with the plasma membrane nor
      delivered DNA into the nucleus. Thus, it is understandable that the unsaturated
      fatty acid ratio of MEL-A strongly influences the gene transfection efficiency of
      cationic liposomes.

PMID- 20674727
TI  - Quantitative analysis of crystalline pharmaceuticals in tablets by pattern
      fitting procedure using X-ray diffraction pattern.
AB  - A pattern-fitting procedure using an X-ray diffraction pattern was applied to the
      quantitative analysis of binary system of crystalline pharmaceuticals in tablets.
      Orthorhombic crystals of isoniazid (INH) and mannitol (MAN) were used for the
      analysis. Tablets were prepared under various compression pressures using a
      direct compression method with various compositions of INH and MAN. Assuming that
      X-ray diffraction pattern of INH-MAN system consists of diffraction intensities
      from respective crystals, observed diffraction intensities were fitted to
      analytic expression based on X-ray diffraction theory and separated into two
      intensities from INH and MAN crystals by a nonlinear least-squares procedure.
      After separation, the contents of INH were determined by using the optimized
      normalization constants for INH and MAN. The correction parameter including all
      the factors that are beyond experimental control was required for quantitative
      analysis without calibration curve. The pattern-fitting procedure made it
      possible to determine crystalline phases in the range of 10-90% (w/w) of the INH
      contents. Further, certain characteristics of the crystals in the tablets, such
      as the preferred orientation, size of crystallite, and lattice disorder were
      determined simultaneously. This method can be adopted to analyze compounds whose
      crystal structures are known. It is a potentially powerful tool for the
      quantitative phase analysis and characterization of crystals in tablets and
      powders using X-ray diffraction patterns.

PMID- 20674728
TI  - Bioadhesive nanoparticles of fungal chitosan for oral DNA delivery.
AB  - Chitosan is an ideal candidate for oral DNA delivery due to its mucoadhesive
      properties. Chitosan (CS) produced under GMP conditions from fungal source was
      used to encapsulate a plasmid DNA coding for a reporter gene. Nanoparticles made
      by complex coacervation of CS and DNA had a size around 200 nm, a positive zeta
      potential, a high association of DNA and protected the plasmid against nuclease
      degradation. Their transfection ability was assessed in differentiated intestinal
      Caco-2 cells. An N/P ratio of 4 and a DNA concentration of 8 microg/ml were the
      optimal conditions leading to a transfection efficiency similar to the one
      reached with polyethyleneimine (PEI)-DNA complexes without cytotoxicity. M cells
      in monolayers influenced DNA uptake up to 8 microg of DNA/ml when complexed with
      CS. Fungal trimethylchitosan was also tested but the complexes interactions were
      too strong to induce transfection in vitro. Confocal microscopy studies showed
      that CS/DNA and PEI/DNA nanoparticles were found at the apical surface of cell
      monolayers and DNA was co-localized within the nucleus. Quantification seemed to
      show that more DNA was associated with the cells when incubated with CS
      nanoparticles and that the presence of M cells slightly influenced DNA uptake
      when complexed with CS. In conclusion, we developed a new nanocarrier made of
      fungal CS promising for oral gene delivery and oral DNA vaccination.

PMID- 20674729
TI  - Inclusion of the poorly water-soluble drug simvastatin in mesocellular foam
      nanoparticles: drug loading and release properties.
AB  - The purpose of this study was to develop spherical mesocellular foam (MCF) loaded
      with a poorly water-soluble drug, intended to be orally administered, able to
      improve the dissolution rate and enhance the drug loading capacity. Spherical MCF
      with a continuous 3-D pore system was synthesized using Pluronic 123 triblock
      polymer (P123) as a surfactant coupled with cetyltrimethyl ammonium bromide
      (CTAB) as a co-surfactant. A model drug, simvastatin (SV), was loaded onto
      spherical MCF via a procedure involving a combination of adsorption equilibrium
      and solvent evaporation. The drug release rate and the drug loading efficiency of
      spherical MCF were compared with those of fibrous SBA-15. Investigations using
      nitrogen adsorption, scanning electron microscopy (SEM), transmission electron
      microscopy (TEM), powder X-ray diffraction (PXRD), differential scanning
      calorimetry (DSC), thermogravimetric analysis (TGA) and HPLC demonstrated the
      successful incorporation of SV into the MCF host. It was found that spherical MCF
      has a high drug loading efficiency up to 37.5%, and higher than that of fibrous
      SBA-15 with a pore diameter of 6.5 nm. It is worth noting that fast release rate
      of SV was obtained from spherical MCF compared with SBA-15 and pure crystalline
      SV using enzyme-free simulated intestinal fluid (SIF, pH 6.8).

PMID- 20674730
TI  - Preparation, characterization and in vivo pharmacodynamic evaluation of
      thymopentin loaded poly(lactide acid)/poly(lactide-co-glycolide acid) implants.
AB  - To avoid the clinical inconvenience of repeated injection of the immune modulator
      thymopentin (TP5), biodegradable implants comprising a mixed polymer matrix of
      poly(lactide acid) (PLA) and poly(lactide-co-glycolide acid) (PLGA) were produced
      using a simple extrusion method. Drug release from these TP5-loaded implants was
      characterized both in vitro and in vivo. Pharmacodynamic studies were carried out
      in immunosuppressed rats using the ratio of CD4(+)/CD8(+) cells, determined by
      flow cytometry, as an index of immunity. The results indicated that the
      entrapment efficiency of the implants was greater than 98%, but the release rate
      of TP5 depended on the drug loading. Implants containing less than 10% TP5 showed
      consistent release over 30 days, with low burst-release both in vitro and in
      vivo. Improved immunity and survival rates were observed in rats treated by TP5
      injection and in rats given middle-to-high dose implants. When the release of TP5
      exceeded 0.1 mg/kg body weight/day the CD4(+)/CD8(+) ratios increased in the 3
      weeks after implantation, reaching a maximum (91.6% of the normal level) by the
      end of the third week. The TP5-loaded implants presented here provide a promising
      alternative to injections and the results support the further development of
      controlled-release TP5 formulations.

PMID- 20674731
TI  - Further study of (+/-)-mefloquinium chloride solvates. Crystal structures of the
      hemihydrate and monohydrate of (+/-)-mefloquinium chloride, from data collected
      at 120 K.
AB  - The crystal structure of a monohydrate of (+/-)-mefloquinium chloride, (+/-)
      [MEFHCl.(H(2)O)], has been obtained from data collected at 120 K. Further details
      of the crystal structure of a hemihydrate, (+/-)-[MEFHCl*(1/2)(H(2)O)],
      previously determined at room temperature, are also reported from data collected
      at 120 K. The structural data, along with X-ray powder patterns, infrared spectra
      (both mid and near IR ranges) and DSC data, provide definitive evidence for the
      two hydrates. Further attempts to completely resolve the crystal structure of a
      tetragonal solvated phase failed due to the considerable disorder, involving the
      solvates, either water or methanol, even at 120 K, however X-ray powder pattern
      and infrared spectral and DSC data for this phase are also reported. Comparisons
      of the data obtained for the hydrates in this study, with X-ray powder patterns
      and mid-infrared spectra of previously reported forms of (+/-)-mefloquinium
      chloride have highlighted erroneous assignments and allowed structural
      identification of previously and differently designated forms.

PMID- 20674732
TI  - Nanocrystals: industrially feasible multifunctional formulation technology for
      poorly soluble actives.
AB  - Poor solubility of new drugs and their related low oral bioavailability and
      general delivery problems are becoming a major challenge. Nanocrystals being a
      kind of "universal" formulation approach for these molecules are reviewed in this
      paper regarding the industrial feasibility, i.e. industrially available
      production processes (bottom-up and top-down technologies), regulatory aspects
      and nanotoxicology. This article also includes second generation nanocrystals
      (<<100 nm) as smartCrystals. The status of products on the market and in clinical
      phases is presented. The different special features of nanocrystals, which are
      exploited in different products, are described (tablets, capsule, aqueous
      nanosuspension). The main focus is given for oral and intravenous products.
      However, the potential and delivery strategies for other administration routes
      are discussed, i.e. dermal and mucosal, ocular, pulmonary and targeted delivery
      (e.g. via differential protein adsorption to the brain). In addition, the
      potential of the nanocrystal technology for delivery of poorly soluble, non
      pharmaceutical actives is highlighted, i.e. in cosmetics or nutraceuticals.

PMID- 20674733
TI  - What breaks a melody: perceiving F0 and intensity sequences with a cochlear
      implant.
AB  - Pitch perception has been extensively studied using discrimination tasks on pairs
      of single sounds. When comparing pitch discrimination performance for normal
      hearing (NH) and cochlear implant (CI) listeners, it usually appears that CI
      users have relatively poor pitch discrimination. Tasks involving pitch sequences,
      such as melody perception or auditory scene analysis, are also usually difficult
      for CI users. However, it is unclear whether the issue with pitch sequences is a
      consequence of sound discriminability, or if an impairment exists for sequence
      processing per se. Here, we compared sequence processing abilities across
      stimulus dimensions (fundamental frequency and intensity) and listener groups
      (NH, CI, and NH listeners presented with noise-vocoded sequences). The sequence
      elements were firstly matched in discriminability, for each listener and
      dimension. Participants were then presented with pairs of sequences, constituted
      by up to four elements varying on a single dimension, and they performed a
      same/different task. In agreement with a previous study (Cousineau et al., 2009)
      fundamental frequency sequences were processed more accurately than intensity
      sequences by NH listeners. However, this was not the case for CI listeners, nor
      for NH listeners presented with noise-vocoded sequences. Intensity sequence
      processing was, nonetheless, equally accurate in the three groups. These results
      show that the reduced pitch cues received by CI listeners do not only elevate
      thresholds, as previously documented, but also affect pitch sequence processing
      above threshold. We suggest that efficient sequence processing for pitch requires
      the resolution of individual harmonics in the auditory periphery, which is not
      achieved with the current generation of implants.

PMID- 20674734
TI  - Ethnomedicinal study of plants used by Sheko ethnic group of Ethiopia.
AB  - AIM OF THE STUDY: This study was conducted to document and evaluate knowledge on
      medicinal plant use by Sheko ethnic group in Southwest Ethiopia. MATERIALS AND
      METHODS: Interviews and ranking exercises were the main methods employed to
      collect the ethnobotanical data. Fidelity level (FL) values were calculated for
      claimed Sheko medicinal plants to estimate their healing potentials. RESULTS:
      Seventy-one Sheko medicinal plants were reported, the majority of which were used
      to treat skin and gastro-intestinal ailments. Ocimum lamiifolium, Phytolacca
      dodecandra, Amaranthus dubius and Amaranthus graecizans were the medicinal plants
      assigned with the highest FL values, a possible indication of their better
      healing potential. The majority of Sheko medicinal plants were found to be herbs,
      and leaf was the most preferred plant part in remedy preparations. The study
      indicated that men, older people and illiterate ones had better knowledge of
      medicinal plants use as compared to women, younger people and literate ones,
      respectively. CONCLUSIONS: The study showed that the Sheko people have rich
      knowledge of medicinal plant use. This knowledge is however, currently threatened
      mainly due to acculturation. Awareness should thus be created among Sheko
      community by concerned bodies regarding the usefulness of their medical practice.
      The efficacy and safety of the claimed medicinal plants need to be evaluated
      before recommending them for a wider use with priority given to those with high
      fidelity level values.

PMID- 20674735
TI  - Increased virulence using engineered protease-chitin binding domain hybrid
      expressed in the entomopathogenic fungus Beauveria bassiana.
AB  - Insect cuticles consist mainly of interlinked networks of proteins and the highly
      insoluble polysaccharide, chitin. Entomopathogenic fungi, such as Beauveria
      bassiana, invade insects by direct penetration of host cuticles via the action of
      diverse hydrolases including proteases and chitinases coupled to mechanical
      pressure. In order to better target cuticle protein-chitin structures and
      accelerate penetration speed, a hybrid protease (CDEP-BmChBD) was constructed by
      fusion of a chitin binding domain BmChBD from Bombyx mori chitinase to the C
      terminal of CDEP-1, a subtilisin-like protease from B. bassiana. Compared to the
      wild-type, the hybrid protease was able to bind chitin and released greater
      amounts of peptides/proteins from insect cuticles. The insecticidal activity of
      B. bassiana was enhanced by including proteases, CDEP-1 or CDEP:BmChBD produced
      in Pichia pastoris, as an additive, however, the augment effect of CDEP:BmChBD
      was significantly higher than that of CDEP-1. Expression of the hybrid protease
      in B. bassiana also significantly increased fungal virulence compared to wild
      type and strains overexpressing the native protease. These results demonstrate
      that rational design virulence factor is a potential strategy for strain
      improvement by genetic engineering.

PMID- 20674736
TI  - Lower respiratory tract infection in cynomolgus macaques (Macaca fascicularis)
      infected with group A Streptococcus.
AB  - Group A Streptococcus (GAS), a human-specific pathogen, is best known for causing
      pharyngitis ("strep-throat") and necrotizing fasciitis ("flesh-eating disease").
      However, the organism is also an uncommon but important cause of community
      acquired bronchopneumonia, an infection with an exceptionally high mortality
      rate. Inasmuch as little is known about the molecular pathogenesis of GAS lower
      respiratory tract infection, we sought to develop a relevant human infection
      model. Nine cynomolgus macaques were infected by intra-bronchial instillation of
      either sterile saline or GAS (10(5) or 10(7) CFU). Animals were continuously
      monitored and sacrificed at five days post-inoculation. Serial bronchial alveolar
      lavage specimens and tissues collected at necropsy were used for histologic and
      immunohistochemical examination, quantitative microbial culture, lung and blood
      biomarker analysis, and in vivo GAS gene expression studies. The lower
      respiratory tract disease observed in cynomolgus macaques mimicked the clinical
      and pathological features of severe GAS bronchopneumonia in humans. This new
      monkey model will be useful for testing hypotheses bearing on the molecular
      pathogenesis of GAS in the lower respiratory tract.

PMID- 20674737
TI  - Neural aspects of immunomodulation: focus on the vagus nerve.
AB  - Inflammation and immunity have been implicated in a wide variety of diseases and
      disorders ranging from Alzheimer's disease to cardiovascular disease to
      hemorrhagic shock. In this review, we will briefly consider the evidence for the
      neural concomitants of immunomodulation. First, we will briefly review the
      anatomy and physiology of neural-immune communication. Evidence for the
      somatotopic organization of the vagus nerve and for pain processes suggests that
      such an organization may be relevant for the investigation of the neural
      concomitants of immunity. Then we will provide an overview of what is known from
      both animal and human studies including neuroimaging and clinical studies.
      Finally, we will discuss some of the challenges and opportunities in this
      exciting area of investigation.

PMID- 20674738
TI  - Stimulation of beta2-adrenergic receptors inhibits calcineurin activity in CD4(+)
      T cells via PKA-AKAP interaction.
AB  - The sympathetic nervous system (SNS) is able to modulate immune functions via
      adrenoceptor-dependent mechanisms. Activation of beta2-adrenergic receptors (AR)
      on CD4(+) T lymphocytes has been shown to inhibit Th1-cytokine production and
      cell proliferation. Here, we investigated the role of the calcium/calmodulin
      dependent protein phosphatase calcineurin (CaN), a key element of the T cell
      receptor (TCR)-signaling pathway, in beta2-AR-mediated suppression of T cell
      function. Purified rat splenic CD4(+) T cells were stimulated with anti-CD3/anti
      CD28 in presence or absence of the beta2-AR agonist terbutaline (TERB). Treatment
      with TERB induced a dose-dependent inhibition of cellular CaN activity, along
      with a reduction in IL-2 and IFN-gamma production, and T cell proliferation. Co
      administration of the beta-AR antagonist nadolol abolished these effects.
      Blockade of the cAMP-dependent protein kinase A (PKA) with the inhibitor H-89
      completely prevented TERB-induced CaN inhibition. However, a receptor-independent
      rise in the second messenger cAMP was not sufficient to suppress CaN activity.
      Disruption of the interaction between PKA and A-kinase anchoring protein (AKAP)
      by the inhibitor peptide St-Ht31 fully blocked TERB-induced CaN inhibition,
      demonstrating that PKA-AKAP interaction is essential for the beta2-AR-mediated
      CaN inhibition. Taken together, this study provides evidence for a link between
      the beta2-AR and TCR signaling pathways since expression of IL-2 and IFN-gamma in
      activated T cells largely depends on dephosphorylation of the transcription
      factor NFAT by CaN, and identifies a novel intracellular mechanism that can lead
      to downregulation of T cell function after SNS activation.

PMID- 20674739
TI  - mamO and mamE genes are essential for magnetosome crystal biomineralization in
      Magnetospirillum gryphiswaldense MSR-1.
AB  - Four non-magnetic mutants of Magnetospirillum gryphiswaldense strain MSR-1 were
      isolated by transposon mutagenesis and found to contain interruption of either
      the mamO or mamE gene within the mamAB operon. Studies indicated that mamO and
      mamE genes are essential for magnetosome crystal biomineralization in MSR-1. This
      is the first report of a single gene (mamO or mamE) whose mutation affects
      crystal biomineralization in MSR-1.

PMID- 20674740
TI  - The polypeptide core of Microcin E492 stably associates with the mannose permease
      and interferes with mannose metabolism.
AB  - Microcin E492 (MccE492) is an antibacterial protein whose activity on target
      cells requires ManYZ, the inner membrane component of the mannose permease. We
      show here that MceA, the polypeptide core of MccE492, stably associates with
      ManYZ both in the presence and in the absence of MceB, the MccE492 immunity
      protein. The two known physiological activities of the mannose permease were
      assayed in cells co-expressing MceA and MceB. Under these conditions, growth on
      mannose as the sole carbon source is prevented; this was not observed in cells
      expressing only MceB. In contrast, susceptibility to bacteriophage lambda
      infection was not affected.

PMID- 20674741
TI  - The many faces of EMMPRIN - roles in neuroinflammation.
AB  - The central nervous system (CNS) is a relatively immune-privileged organ, wherein
      a well-instated barrier system (the blood-brain barrier) prevents the entry of
      blood cells into the brain with the exception of regular immune surveillance
      cells. Despite this tight security immune cells are successful in entering the
      CNS tissue where they result in states of neuroinflammation, tissue damage and
      cell death. Various components of the blood-brain barrier and infiltrating cells
      have been examined to better understand how blood cells are able to breach this
      secure barrier. Proteases, specifically matrix metalloproteinases (MMP), have
      been found to be the common culprits in most diseases involving
      neuroinflammation. MMPs secreted by infiltrating cells act specifically upon
      targets on various components of the blood-brain barrier, compromising this
      barrier and allowing cell infiltration into the CNS. Extracellular matrix
      metalloproteinase inducer (EMMPRIN) is an upstream inducer of several MMPs and is
      suggested to be the master regulator of MMP production in disease states such as
      cancer metastasis. EMMPRIN in the context of the CNS is still relatively
      understudied. In this review we will introduce EMMPRIN, discuss its ligands and
      roles in non-CNS conditions that can help implicate its involvement in CNS
      disorders, showcase its expression within the CNS in healthy and disease
      conditions, elucidate its ligands and receptors, and briefly discuss the emerging
      roles it plays in various diseases of the CNS involving inflammation.

PMID- 20674742
TI  - New insights into the role of mitochondrial dysfunction and protein aggregation
      in Parkinson's disease.
AB  - Parkinson's disease (PD) is a common neurodegenerative movement disorder that
      affects increasing number of elderly in the world population. The disease is
      caused by a selective degeneration of dopaminergic neurons in the substantia
      nigra pars compacta with the molecular mechanism underlying this
      neurodegeneration still not fully understood. However, various studies have shown
      that mitochondrial dysfunction and abnormal protein aggregation are two of the
      major contributors for PD. In fact this notion has been supported by recent
      studies on genes that are linked to familial PD (FPD). For instance, FPD linked
      gene products such as PINK1 and parkin have been shown to play critical roles in
      the quality control of mitochondria, whereas alpha-synuclein has been found to be
      the major protein aggregates accumulated in PD patients. These findings suggest
      that further understanding of how dysfunction of these pathways in PD will help
      develop new approaches for the treatment of this neurodegenerative disorder.

PMID- 20674743
TI  - MS and the B cell controversy.
AB  - The contribution of B cells and their products to the pathogenesis of MS has long
      been debated. The presence of B cells, plasma cells and excess immunoglobulins in
      MS lesions and in the cerebrospinal fluid of MS patients implicate the humoral
      immune system in the disease. Correlations of higher levels of CSF B cells and
      immunoglobulins found in some studies with a more aggressive clinical course of
      MS have bolstered the notion that the humoral immune system is involved in MS
      pathogenesis. However, until the advent of rituximab, a monoclonal antibody
      therapy that specifically lyses B cells, confirmation of the key role of B cells
      and their products in MS had been lacking. Development of this therapeutic
      monoclonal antibody to CD20, a cell surface molecule confined to B cells, allowed
      determination of the effects of B cell depletion. Perhaps somewhat unexpectedly,
      depletion of circulating B cells led to rapid and profound reduction in
      gadolinium enhancing lesions on brain MRI in three separate studies in relapsing
      MS subjects. When examined, depletion of B cells in the blood was accompanied by
      depletion of B cells in CSF. Notably, reduction of enhancing brain lesions was
      not accompanied by reduction in CSF immunoglobulins. Whether the critical role of
      B cells occurs in the periphery, in the CNS, or in both locations has not yet
      been determined.

PMID- 20674744
TI  - Assessment of evidence for a protective role of vitamin D in multiple sclerosis.
AB  - Evidence for a role of vitamin D insufficiency in determining risk in Multiple
      Sclerosis (MS) is supported by studies in both pediatric- and adult-onset
      patients. The potential role of vitamin D in modulating MS disease activity is an
      area of active clinical trials research, and the possibility of primary disease
      prevention with vitamin D supplementation in early life is an emerging concept.
      With Sir Austin Bradford Hill's criteria as a framework, the present review
      assesses the evidence for a causal relationship between vitamin D insufficiency
      and the pathobiology of MS, and discusses rationale for future clinical trials
      with vitamin D.

PMID- 20674745
TI  - Mutational hotspots in electron transfer flavoprotein underlie defective folding
      and function in multiple acyl-CoA dehydrogenase deficiency.
AB  - We have carried out an extensive in silico analysis on 18 disease associated
      missense mutations found in electron transfer flavoprotein (ETF), and found that
      mutations fall essentially in two groups, one in which mutations affect protein
      folding and assembly, and another one in which mutations impair catalytic
      activity and disrupt interactions with partner dehydrogenases. We have further
      experimentally analyzed three of these mutations, ETFbeta-p.Cys42Arg, ETFbeta
      p.Asp128Asn and ETFbeta-p.Arg191Cys, which have been found in homozygous form in
      patients and which typify different scenarios in respect to the clinical
      phenotypes. The ETFbeta-p.Cys42Arg mutation, related to a severe form of multiple
      acyl-CoA dehydrogenase deficiency (MADD), affects directly the AMP binding site
      and intersubunit contacts and impairs correct protein folding. The two other
      variations, ETFbeta-p.Asp128Asn and ETFbeta-p.Arg191Cys, are both associated with
      mild MADD, but these mutations have a different impact on ETF. Although none
      affects the overall alpha/beta fold topology as shown by far-UV CD, analysis of
      the purified proteins shows that both have substantially decreased enzymatic
      activity and conformational stability. Altogether, this study combines in silico
      analysis of mutations with experimental data and has allowed establishing
      structural hotspots within the ETF fold that are useful to provide a rationale
      for the prediction of effects of mutations in ETF.

PMID- 20674746
TI  - The selective estrogen receptor modulator raloxifene inhibits cardiac delayed
      rectifier potassium currents and voltage-gated sodium current without QTc
      interval prolongation.
AB  - Raloxifene is widely used in the treatment of postmenopausal osteoporosis and
      also has been shown to be cardioprotective. The effect of raloxifene on cardiac
      ion channels is not fully understood. The present study investigated whether
      raloxifene could affect the cloned hERG channel (I(hERG)) and recombinant human
      cardiac KCNQ1/KCNE1 channel (I(Ks)) stably expressed in HEK 293 cells using a
      patch-clamp technique. Raloxifene blocked I(hERG) with an IC(50) of 1.1 MUM and
      decreased I(Ks) (IC(50): 4.8 MUM) without affecting activation kinetics. In
      addition, raloxifene significantly decreased I(Na) (IC(50): 2.8 MUM) in guinea
      pig ventricular myocytes. However, this drug (1 MUM) did not increase QRS and QTc
      interval in isolated guinea pig hearts. These results demonstrate that
      raloxifene, despite its inhibitory action on delayed rectifier potassium
      currents, does not prolong ECG QTc interval, suggesting that raloxifene is likely
      a safe selective estrogen receptor modulator with less cardiac toxicity.

PMID- 20674747
TI  - Expression, purification and functional characterization of recombinant Zucchini
      yellow mosaic virus HC-Pro.
AB  - HC-Pro is a helper component-proteinase which acts as a multifunctional protein
      in the potyviral life cycle. Apart from its proteolytic activity, HC-Pro has the
      capacity to bind duplex small RNAs (sRNAs). To investigate HC-Pro-mediated sRNA
      binding in vitro, high amounts of purified protein are required. For this
      purpose, the Zucchini yellow mosaic virus (ZYMV) HC-Pro was expressed as a fusion
      with hexa-histidine (6xHis) or maltose-binding protein (MBP) in Escherichia coli.
      The expressed fusion proteins were purified by affinity chromatography. 6xHis:HC
      Pro and MBP:HC-Pro were partially soluble. Electrophoretic mobility-shift assays
      demonstrated that only MBP:HC-Pro exhibits the sRNA binding activity. The
      recombinant HC-Pro bound 21 bp siRNAs as well as 19 bp and 24 bp siRNAs. A point
      mutation in the highly conserved FRNK box produced the HC-Pro(FINK) protein,
      previously shown to be associated with reduced viral symptoms and weak sRNA
      binding. In this study, sRNA binding of the MBP:HA-HC-Pro(FINK) was not
      detectable. The high yield of purified HC-Pro offers the possibility to study the
      biochemistry of the protein in detail.

PMID- 20674748
TI  - Expression and purification of 15 kDa granulysin utilizing an insect cell
      secretion system.
AB  - Granulysin is an antimicrobial and proinflammatory protein expressed in activated
      human T cells and natural killer cells. A single mRNA produces the 15 kDa isoform
      which is then cleaved at the amino and carboxy termini to produce the 9 kDa
      isoform. Recombinant 9 kDa granulysin has been studied in detail but little is
      known about the function of the 15 kDa isoform, and no protocol has been
      published describing expression and purification of this form. Two commercially
      available preparations of the recombinant 15 kDa granulysin contain tags that may
      affect function. Here we describe for the first time a method to produce 15 kDa
      granulysin as a secreted protein from insect cells. The 15 kDa granulysin is
      purified using a HiTrap Heparin column and a Resource S column. A typical a yield
      of purified 15 kDa granulysin is 0.6 mg/L of insect cell supernatant.

PMID- 20674749
TI  - A Monte Carlo method for locally multivariate brain mapping.
AB  - Locally multivariate approaches to functional brain mapping offer a highly
      appealing complement to conventional statistics, but require restrictive region
      of-interest hypotheses, or, in exhaustive search forms (such as the "searchlight"
      algorithm; Kriegeskorte et al., 2006), are excessively computer intensive. We
      therefore propose a non-restrictive, comparatively fast yet highly sensitive
      method based on Monte Carlo approximation principles where locally multivariate
      maps are computed by averaging across voxelwise condition-discriminative
      information obtained from repeated stochastic sampling of fixed-size search
      volumes. On simulated data containing discriminative regions of varying size and
      contrast-to-noise ratio (CNR), the Monte Carlo method reduced the required
      computer resources by as much as 75% compared to the searchlight with no
      reduction in mapping performance. Notably, the Monte Carlo mapping approach not
      only outperformed the general linear method (GLM), but also produced higher
      discriminative voxel detection scores than the searchlight irrespective of
      classifier (linear or nonlinear support vector machine), discriminative region
      size or CNR. The improved performance was explained by the information-average
      procedure, and the Monte Carlo approach yielded mapping sensitivities of a few
      percent lower than an information-average exhaustive search. Finally, we
      demonstrate the utility of the algorithm on whole-brain, multi-subject functional
      magnetic resonance imaging (fMRI) data from a tactile study, revealing that the
      central representation of gentle touch is spatially distributed in somatosensory,
      insular and visual regions.

PMID- 20674751
TI  - Origin and genetic diversity of Chinese domestic ducks.
AB  - China is particularly rich in duck genetic resources. In order to reveal the
      genetic diversity and origin of Chinese domestic duck, the 667 bp control region
      of mitochondrial DNA of 238 domestic ducks from 26 indigenous breeds, 25 wild
      mallards and nine spot-billed ducks were sequenced and analyzed them together
      with the published data for 12 mallards and nine spot-billed ducks. The haplotype
      diversity (Hd, 0.645) and average nucleotide diversity (Pi, 0.115%) indicate low
      genetic diversity of Chinese domestic ducks. The NJ phylogenetic tree and reduced
      median-joining network chart were constructed using a total of 72 haplotypes. The
      genetic contribution of mallard (Anas platyrhynchos) can be detected in most of
      Chinese indigenous duck breeds and that of spot-billed duck (Anas zonorhyncha)
      can also be detected in few Chinese indigenous duck breeds. The results indicated
      that the Chinese domestic ducks mainly derived from mallard (A. platyrhynchos)
      and few derived from spot-billed duck (A. zonorhyncha).

PMID- 20674750
TI  - CLADA: cortical longitudinal atrophy detection algorithm.
AB  - Measurement of changes in brain cortical thickness is useful for the assessment
      of regional gray matter atrophy in neurodegenerative conditions. A new
      longitudinal method, called CLADA (cortical longitudinal atrophy detection
      algorithm), has been developed for the measurement of changes in cortical
      thickness in magnetic resonance images (MRI) acquired over time. CLADA creates a
      subject-specific cortical model which is longitudinally deformed to match images
      from individual time points. The algorithm was designed to work reliably for
      lower resolution images, such as the MRIs with 1*1*5 mm(3) voxels previously
      acquired for many clinical trials in multiple sclerosis (MS). CLADA was evaluated
      to determine reproducibility, accuracy, and sensitivity. Scan-rescan variability
      was 0.45% for images with 1mm(3) isotropic voxels and 0.77% for images with 1*1*5
      mm(3) voxels. The mean absolute accuracy error was 0.43 mm, as determined by
      comparison of CLADA measurements to cortical thickness measured directly in post
      mortem tissue. CLADA's sensitivity for correctly detecting at least 0.1mm change
      was 86% in a simulation study. A comparison to FreeSurfer showed good agreement
      (Pearson correlation=0.73 for global mean thickness). CLADA was also applied to
      MRIs acquired over 18 months in secondary progressive MS patients who were imaged
      at two different resolutions. Cortical thinning was detected in this group in
      both the lower and higher resolution images. CLADA detected a higher rate of
      cortical thinning in MS patients compared to healthy controls over 2 years. These
      results show that CLADA can be used for reliable measurement of cortical atrophy
      in longitudinal studies, even in lower resolution images.

PMID- 20674752
TI  - Molecular phylogenetics of moray eels (Muraenidae) demonstrates multiple origins
      of a shell-crushing jaw (Gymnomuraena, Echidna) and multiple colonizations of the
      Atlantic Ocean.
AB  - Moray eels (Muraenidae) are apex predators on coral reefs around the world, but
      they are not well studied because their cryptic habitats and occasionally
      aggressive behaviors make them difficult to collect. We provide a molecular
      phylogeny of moray eels including 44 species representing two subfamilies, eight
      genera, and all tropical ocean basins. Phylogenetic relationships among these
      taxa are estimated from portions of mitochondrial loci cytochrome b (632 bp) and
      cytochrome oxidase subunit 1 (596 bp), and portions of the nuclear loci RAG-1
      (421 bp) and RAG-2 (754 bp). We test four sets of contrasting phylogenetic
      hypotheses using Bayes Factors, Shimodaira-Hasegawa tests, and Templeton tests.
      First, our results support the subfamily-level taxonomic distinction between true
      morays (Muraeninae) and snakemorays (Uropterygiinae), statistically rejecting
      hypotheses of non-monophyly for each subfamily. Second, we reject a monophyletic
      grouping of the genera Gymnomuraena and Echidna, which share a durophagous (shell
      crushing) cranial morphology and dentition, indicating that the durophagous
      characters are not homologous. Third, we demonstrate that durophagous feeding
      habits and associated morphological characters have evolved in parallel in an
      ancestor of Gymnomuraena and at least three additional times within the genus
      Echidna. Finally, the tree topology indicates multiple invasions of the Atlantic
      from the Indo-Pacific, one of these occurring immediately prior to formation of
      the Isthmus of Panama approximately 2.8 MYA (million years ago) and one or two
      others occurring in the early to mid Miocene. Cladogenesis occurring within the
      Atlantic during the mid Miocene and Pliocene also contributed to moray species
      diversity. These data include a pair of sister species separated by the Isthmus
      of Panama, allowing a time-calibrated tree with an estimated crown age for
      Muraenidae at between 41 and 60 MYA, consistent with fossil evidence. Most
      lineage accumulation within morays occurred from the late Oligocene (24-27 MYA)
      through the Miocene (5-23 MYA) to the late Pliocene (~ 2.5 MYA).

PMID- 20674753
TI  - Phylogenetic position of the enigmatic Lepidogalaxias salamandroides with comment
      on the orders of lower euteleostean fishes.
AB  - This study examines phylogenetic placement of the enigmatic Western Australian
      Lepidogalaxias, and extends previous studies by including eight new taxa to
      enable re-examination phylogenetic relationships of lower euteleostean fishes at
      the ordinal level, based on mitochondrial genomes from 39 ingroup taxa and 17
      outgroups. Our results suggest that Lepidogalaxias occupies a basal position
      among all euteleosts, in contrast with earlier hypotheses that variously
      suggested a closer relationship to esocid fishes, or to the galaxiid Lovettia. In
      addition our evidence shows that Osmeriformes should be restricted Retropinnidae,
      Osmeridae, Plecoglossidae and Salangidae. This reduced Osmeriformes is supported
      in our results as the sister group of Stomiiformes. Galaxiidae, which is often
      closely linked to Osmeriformes, emerges as sister group of a combined
      Osmeriformes, Stomiiformes, Salmoniformes, Esociformes and Argentiformes, and we
      give Galaxiiformes the rank of order to include all remaining galaxioid fishes
      (Galaxias and allied taxa, Aplochiton and Lovettia). Our results also support a
      sister group relationship between Salmoniformes and Esociformes, which are
      together the sister group of Argentiniformes.

PMID- 20674754
TI  - Colonization of segmented filamentous bacteria and its interaction with the
      luminal IgA level in conventional mice.
AB  - Segmented filamentous bacteria (SFB) colonize in the ileum. They promote the
      development of intraepithelial lymphocytes and immunoglobulin A (IgA)-producing
      cells in the small intestine. In SFB-monoassociated mice, changes in SFB
      colonization of the small intestine were related to the level of IgA derived from
      maternal milk during the suckling period and self-produced in the small intestine
      after weaning. In this study, we investigated whether or not maternal and
      neonatal IgA influence the colonization of SFB in conventional mice from 18 to
      105 days old. The pups were forcedly weaned at 20 days old. SFB could be detected
      in the distal small intestine after day 22, and their number rapidly reached a
      maximum on day 28. Thereafter, they gradually declined to one-fourth of the
      maximum level. The lowest concentrations of IgA in the small intestinal and cecal
      contents were detected on day 22. Thereafter, they increased as the age of the
      mice increased. The expression of the polymeric immunoglobulin receptor gene in
      the distal small intestine increased after weaning. These results suggested that
      the colonization of SFB in the pre-weaning and post-weaning periods might be
      prevented with IgA derived from maternal milk and self-produced IgA,
      respectively.

PMID- 20674755
TI  - Prognostic factors for outcomes of pediatric patients with refractory or relapsed
      acute leukemia undergoing allogeneic progenitor cell transplantation.
AB  - Allogeneic stem cell transplantation (SCT) is the only curative therapy for
      patients with refractory or relapsed acute leukemia, although the prognosis
      remains poor. Few reports have described outcomes of SCT in pediatric patients
      with refractory acute leukemia. To identify prognostic factors for these
      patients, we retrospectively evaluated SCT outcomes for advanced acute leukemia
      in 82 pediatric patients from 3 transplant units in Nagoya City between 1990 and
      2008. Median age at transplantation was 8 years (range, 0.5-17 years).
      Transplantation was performed in the first refractory relapse for 53 patients
      (64.6%), in the second or subsequent relapse for 16 patients (19.5%), and during
      primary induction failure for 13 patients (15.9%). Only 4 patients (4.9%)
      underwent transplantation in the untreated first relapse, and 39 patients (47.6%)
      received unrelated donor progenitor cells. Of the 82 patients, 61 died (77.9%),
      with a median survival of 7.1 months (95% confidence interval [CI], 4.2-10.0
      months). Median disease-free survival (DFS) was 4.7 months (95% CI, 2.6-6.9
      months). In multivariate analysis, peripheral blood blasts, cord blood
      transplantation, and more than 3 courses of previous salvage chemotherapy were
      predictive of DFS. These results support the notion that allogeneic SCT offers
      only a small chance of cure for most pediatric patients with refractory or
      relapsed acute leukemia, and suggest that reduction of the leukemia burden and
      earlier optimal timing of transplantation are essential for long-term survival
      even in patients with refractory acute leukemia.

PMID- 20674756
TI  - One-antigen mismatched related versus HLA-matched unrelated donor hematopoietic
      stem cell transplantation in adults with acute leukemia: Center for International
      Blood and Marrow Transplant Research results in the era of molecular HLA typing.
AB  - Approximately 13% of patients lacking an HLA-identical sibling have a one-antigen
      mismatched related donor (MMRD). Historically, outcomes from the use of a one
      antigen MMRD were considered equivalent to those from the use of a matched
      unrelated donor (UD). Recent improvements in UD stem cell transplantation (SCT)
      resulting from better molecular HLA matching justifies investigating whether UD
      should be preferred over MMRD in adult patients with acute leukemia. Here, we
      compared the outcomes of MMRD (n = 89) and HLA-A, -B, -C, and -DRB1 allele
      matched UD (n = 700) SCT reported to the Center for International Blood and
      Marrow Transplant Research between 1995 and 2005. The patients underwent
      transplantation for acute myelogenous leukemia or acute lymphoblastic leukemia in
      first or second complete remission. Donor type was not associated with
      hematologic recovery. Univariate and multivariate comparisons of MMRD versus HLA
      matched UD transplants showed no statistically significant differences in overall
      survival, disease-free survival, treatment-related mortality, relapse, or 100-day
      grade III-IV acute graft-versus-host disease (GVHD). MMRD SCT was associated with
      a lower rate of chronic GVHD at 1 year (35% vs 47%; P = .03), which was confirmed
      by multivariate analysis (relative risk, 0.58; 95% confidence interval, 0.39
      0.85; P < .01). According to our data, HLA-matched UD and MMRD SCT are associated
      with comparable survival. Given that less chronic GVHD was observed in the MMRD
      transplantations, this option, when available, remains the first choice in
      patients with acute leukemia without an HLA-identical sibling in need of
      allogeneic SCT.

PMID- 20674757
TI  - Intravenous busulfan plus melphalan is a highly effective, well-tolerated
      preparative regimen for autologous stem cell transplantation in patients with
      advanced lymphoid malignancies.
AB  - We investigated the administration of intravenous (i.v.) busulfan (Bu) combined
      with melphalan (Mel) in patients with advanced lymphoid malignancies undergoing
      autologous stem cell transplantation. Bu 130 mg/m(2) was infused daily for 4
      days, either as a fixed dose per body surface area (BSA), or to target an average
      daily area under the curve of 5000 MUmol-min, determined by a test dose of i.v.
      Bu at 32 mg/m(2) given 48 hours prior to the high-dose regimen, followed by a
      rest day, followed by 2 daily doses of Mel at 70 mg/m(2). Stem cells were infused
      the following day. Eighty patients had i.v. Bu delivered per test dose guidance.
      The median daily systemic Bu exposure was 4867 MUmol-min. One hundred two
      patients (Hodgkin lymphoma n = 49, non-Hodgkin lymphoma n = 12, multiple myeloma
      = 41) with a median age of 44 years (range: 19-65 years) were treated. The 2-year
      overall survival and progression-free survival rates were 85% and 57%,
      respectively, for patients with Hodgkin lymphoma, 67% and 64%, respectively, for
      patients with non-Hodgkin lymphoma, and 82% and 42%, respectively, for patients
      with multiple myeloma. The regimen was very well tolerated with treatment-related
      mortality at 100 days, 1 year, and 2 years of 1%, 3%, and 3%, respectively.
      Intravenous Bu-Mel was well tolerated. Disease control wa encouraging, and should
      be explored in larger phase II studies.

PMID- 20674759
TI  - The effect of a single bolus of exogenous surfactant on lung compliance persists
      until two weeks after treatment in a model of acid aspiration pneumonitis.
AB  - Aspiration pneumonitis, a direct cause of acute lung injury, is associated to a
      severe deterioration of lung function due in part to endogenous surfactant system
      impairment. We evaluated the effects of selective exogenous surfactant
      administration in a murine model of acid-induced lung injury both at short and
      long term. Hydrochloric acid was instilled into the right bronchus of the mice
      (0.1 M, 1.5 ml/kg). Six hours from acid instillation, they received, in the
      injured lung, a 1 ml/kg bolus of porcine surfactant (Curosurf(r)) 40 or 80 mg
      phospholipids/ml (Surf40 or Surf80), or saline (0.9% NaCl, vehicle) Functional,
      biochemical, histological and inflammatory results were obtained 24 h after
      injury. In the Surf80 and vehicle group, lung mechanics and histology were
      assessed again after two weeks. Micro-Computed Tomography scans were performed at
      24 h and two weeks. 24 h after injury in the Surf80 group respiratory system
      compliance and oxygenation were significantly improved compared to the vehicle,
      while neutrophilic fraction in bronchoalveolar lavage was significantly lower.
      Surfactant-treated mice maintained a better compliance and a significantly
      reduced inflammatory infiltrate also two weeks after treatment compared to
      vehicle. Micro-Computed Tomography scan suggested a more pronounced reduction of
      injury in surfactant-treated animals two weeks after injury (p = 0.09). We showed
      a beneficial effect on lung function of a single bolus of exogenous surfactant in
      unilateral acid-induced lung injury up to two weeks after treatment. Our results
      may suggest a role of surfactant replacement in modulating spontaneous evolution
      of injury.

PMID- 20674758
TI  - Reduced-intensity conditioning allogeneic hematopoietic cell transplantation for
      patients with hematologic malignancies who relapse following autologous
      transplantation: a multi-institutional prospective study from the Cancer and
      Leukemia Group B (CALGB trial 100002).
AB  - We prospectively treated 80 patients with relapse of malignancy or secondary
      myelodysplasia after autologous hematopoietic cell transplantation (AHCT) with
      allogeneic HCT (allo-HCT) using a reduced-intensity conditioning regimen of
      fludarabine 150 mg/m(2) plus intravenous busulfan 6.4 mg/kg. Both matched sibling
      (MSD) and unrelated donors (MUD) were allowed. Patients transplanted from MUD
      donors received more intensive graft-versus-host disease (GVHD) prophylaxis,
      including rabbit antithymocyte globulin (ATG) 10 mg/kg, mycophenolate mofetil,
      and an extended schedule of tacrolimus. With a median follow-up of 3.1 years (0.9
      5.8), treatment-related mortality (TRM) at 6 months and 2 years was 8% and 23%,
      respectively. Neither TRM nor the rates of acute GVHD (aGVHD) were different in
      those with sibling or MUD donors. Donor CD3 cell chimerism >90% at day +30 was
      achieved more often in patients with MUD than with matched sibling donors, 70%
      versus 23% (P < .0001). Median event-free suvival was higher in patients who
      achieved early full donor chimerism (14.2 versus 8 months, P = .0395). Allo-HCT
      using this reduced-intensity conditioning regimen can be performed with low TRM
      in patients who have received a prior AHCT. Efforts to improve early donor CD3
      chimerism may improve event-free survival.

PMID- 20674760
TI  - Metabolic rate and specific dynamic action of the Red-legged Honeycreeper, a
      nectar-feeding Neotropical passerine.
AB  - Rate of oxygen consumption (VO(2)) and carbon dioxide production (VCO(2)) were
      measured in the Red-legged Honeycreeper (Cyanerpes cyaneus, mean body mass 14.0+/
      0.1g) at ambient temperatures (T(a)) between 15 degrees C and 35 degrees C to
      determine the basal metabolic rate (BMR). VO(2) in response to the light-dark
      cycle and the specific dynamic action (SDA) effect was also investigated. BMR was
      estimated to be 2.mLO(2) g(-1)h(-1), 10% lower than expected according to the
      Aschoff-Pohl relationship for passerines and 12% higher than expected following
      Mckechnie and Wolf's (2004) equation. Below 25 degrees C, VO(2) was linearly
      related to T(a). Body temperature averaged 40.2 degrees C and was not affected by
      T(a) over the range of temperature tested. The SDA was demonstrated at 20 degrees
      C by a two fold increase in VO(2) compared to pre-feeding levels. The
      honeycreepers showed a marked light-dark VO(2) cycle, with a mean reduction of
      46% at night. During the night, birds rely on their body reserves as deduced from
      the respiratory quotient (RQ) values. Honeycreepers show a metabolic rate higher
      than predicted by allometry, marked diel fluctuations in their metabolic rates
      and a moderate SDA effect despite of the simplicity of nectar as food.

PMID- 20674761
TI  - Effects of acute changes in salinity and temperature on routine metabolism and
      nitrogen excretion in gambusia (Gambusia affinis) and zebrafish (Danio rerio).
AB  - Acute stress may affect metabolism and nitrogen excretion as part of the adaptive
      response that allows animals to face adverse environmental changes. In the
      present paper the acute effects of different salinities and temperatures on
      routine metabolism, spontaneous activity and excretion of ammonia and urea were
      studied in two freshwater fish: gambusia, Gambusia affinis and zebrafish, Danio
      rerio, acclimated to 27 degrees C. The effects on gill morphology were also
      evaluated. Five salinities (0 per thousand, 10 per thousand, 20 per thousand, 30
      per thousand and 35 per thousand) were tested in gambusia, while four salinities
      were used in zebrafish (0 per thousand, 10 per thousand, 20 per thousand and 25
      per thousand). Each salinity acute stress was tested alone or in combination with
      an acute temperature reduction to 20 degrees C. In gambusia, both salinity and
      temperature acute stress strongly stimulated urea excretion. Routine oxygen
      consumption was barely affected by acute salinity or temperature stress, and was
      reduced by the combined effects of temperature and high salinity. Gills
      maintained their structural integrity in all stressing conditions; hyperplasia
      and hypertrophy of mitochondria-rich cells were observed. In zebrafish,
      temperature and salinity acute changes, both alone and in combination, scarcely
      affected any parameter tested. The major effect observed was a reduction of
      nitrogen excretion at 20 degrees C-25 per thousand; under these extreme
      conditions a significant structural disruption of gills was observed. These
      results confirm the high tolerance to acute salinity and temperature stress in
      gambusia, and demonstrate the involvement of urea excretion modulation in the
      stress response in this species.

PMID- 20674762
TI  - Regulation of liver glutamate dehydrogenase by reversible phosphorylation in a
      hibernating mammal.
AB  - Glutamate dehydrogenase (GDH) is a key enzyme that links amino acid and
      carbohydrate metabolism in cells. Regulation is likely most important when
      organisms are confronted with extreme stresses such as the low environmental
      temperatures and lack of food associated with winter. Many small mammals, such as
      Richardson's ground squirrels, Spermophilus richardsonii, cope with these
      conditions by hibernating. Animals enter long periods of profound torpor where
      metabolic rate is greatly suppressed, body temperature drops to near-ambient and
      all metabolic needs must be met from fixed internal body stores of fuels. To
      investigate how GDH is regulated under these conditions, kinetic properties of
      GDH were analyzed in liver from euthermic and torpid squirrels, revealing
      significant differences in V(max), K(m) glutamate, K(a) ADP and inhibition by
      urea between the two forms of GDH. These data suggested an activation of the
      glutamate-oxidizing activity of GDH in the hypometabolic state. Subsequent
      experiments suggested that the molecular basis of the kinetic differences was a
      change in the protein phosphorylation state of GDH between euthermia and torpor.
      Specifically, liver GDH appears to be dephosphorylated and activated when animals
      transition into torpor and this may serve to promote amino acid oxidation to
      contribute to energy production and gluconeogenesis. This is the first study to
      show that mammalian liver GDH can be regulated by reversible phosphorylation,
      providing an important new regulatory mechanism for GDH control.

PMID- 20674763
TI  - [Invasive fungal infection in a patient with Burkitt lymphoma].

PMID- 20674764
TI  - Toll-like receptor 8 and 9 polymorphisms in Crimean-Congo hemorrhagic fever.
AB  - Crimean-Congo hemorrhagic fever (CCHF) is an acute viral hemorrhagic fever. The
      clinical course and outcome of the CCHF infection are different in humans. Toll
      like receptors (TLRs) are a family of pathogen recognition receptors. TLR8 and
      TLR9 contribute to the recognition of viruses. We investigated frequency of TLR8
      Met1Val, TLR8 -129C/G, TLR9 -1486T/C and TLR9 2458G/A polymorphisms in CCHF
      patients and healthy controls. Our study was conducted between June 1 and August
      31, 2007 in Cumhuriyet University Hospital, Turkey. TLR genotypes were detected
      using the PCR-RFLP assay in 85 CCHF patients and 171 healthy controls. We found
      that heterozygous plus homozygous mutant genotypes frequency for TLR8 Met1Val and
      for TLR9 -1486T/C were significantly higher in CCHF patients than controls (p =
      0.038 and p = 0.009, respectively). The frequency of TLR8 -129G/G genotype in the
      fatal CCHF patients was significantly higher than that of the non-fatal patients
      (p = 0.026). The frequency of TLR9 -1486C/C genotype was significantly higher in
      fatal CCHF patients than in healthy controls (p = 0.009) and in patients with
      severe disease compared to non-severe disease (p = 0.044). Our findings suggest
      that TLR8 Met1Val, TLR8 -129C/G, and TLR9 -1486T/C polymorphisms are important on
      clinical course of CCHF disease.

PMID- 20674765
TI  - Protein phosphatase with EF-hand domains 2 (PPEF2) is a potent negative regulator
      of apoptosis signal regulating kinase-1 (ASK1).
AB  - The function of protein phosphatases with EF-hand domains (PPEF) in mammals is
      not known. Large-scale expression profiling experiments suggest that PPEF
      expression may correlate with stress protective responses, cell survival, growth,
      proliferation, or neoplastic transformation. Apoptosis signal regulating kinase-1
      (ASK1) is a MAP kinase kinase kinase implicated in cancer, cardiovascular and
      neurodegenerative diseases. ASK1 is activated by oxidative stress and induces pro
      apoptotic or inflammatory signalling, largely via sustained activation of MAP
      kinases p38 and/or JNK. We identify human PPEF2 as a novel interacting partner
      and a negative regulator of ASK1. In COS-7 or HEK 293A cells treated with
      H(2)O(2), expression of PPEF2 abrogated sustained activation of p38 and one of
      the JNK p46 isoforms, and prevented ASK1-dependent caspase-3 cleavage and
      activation. PPEF2 efficiently suppressed H(2)O(2)-induced activation of ASK1.
      Overexpessed as well as endogenous ASK1 co-immunoprecipitated with PPEF2. PPEF2
      was considerably more potent both as a suppressor of ASK1 activation and as its
      interacting partner as compared to protein phosphatase 5 (PP5), a well-known
      negative regulator of ASK1. PPEF2 was found to form complexes with endogenous
      Hsp70 and to a lesser extent Hsp90, which are also known interacting partners of
      PP5. These data identify, for the first time, a possible downstream signalling
      partner of a mammalian PPEF phosphatase, and suggest that, despite structural
      divergence, PPEF and PP5 phosphatases may share common interacting partners and
      functions.

PMID- 20674766
TI  - A review of Charcot neuroarthropathy of the midfoot and hindfoot: what every
      radiologist needs to know.
AB  - Charcot neuroarthropathy (CN) occurs commonly in diabetic patients in the joints
      of the foot and ankle. Radiologists may be the first to suggest the diagnosis of
      CN and can facilitate prompt intervention and treatment if they are aware of the
      radiographic manifestations of CN and the signs of progression of disease.
      Radiologists should also become aware of the evolving treatment of the disease as
      focus is shifting toward early surgical intervention and limb salvage rather than
      amputation. Knowledge of preoperative assessment, the types of surgeries
      performed, and some of the encountered postoperative complications enable the
      radiologist to facilitate timely intervention by our surgical colleagues and be a
      valuable member of the management team.

PMID- 20674767
TI  - Second-look targeted studies after breast magnetic resonance imaging: practical
      tips to improve lesion identification.
AB  - Second-look studies, so-called because a re-evaluation of the breast is performed
      after review of magnetic resonance imaging (MRI) findings, offer the possibility
      of identifying correlates to MRI-detected lesions that were not previously
      suspected at mammography or ultrasound, thereby permitting immediate biopsy. To
      maximize the identification of ultrasound and mammographic correlates to MRI
      identified lesions, one must carefully review the initial MRI examination as well
      as be cognizant of breast normal anatomy and variations in breast position across
      imaging modalities. We review the steps required for planification and
      realization of a successful second-look evaluation. After a correlate has been
      found and percutaneous biopsy performed, we recommend obtaining a T1-weighted
      noncontrast MRI sequence to verify metallic marker placement at the site of
      biopsy. This step ensures correct correlation between imaging modalities,
      provides immediate feedback for the radiologist, and, in case of error, allows
      the patient to be immediately redirected to repeat biopsy, often under MRI
      guidance. In the case of correct correlation, short-term follow-up is
      recommended, as for other breast percutaneous interventional procedures. We
      propose a simple management algorithm following second-look targeted studies.

PMID- 20674768
TI  - How will you need me, how will you read me, when I'm 64 (or more!)?: volume
      computed tomographic scanning and information overload in the emergency
      department.
AB  - Computed tomographic (CT) scanning technology now employs up to 320 detector rows
      of 0.5-mm width and allows rapid acquisition of isotropic volume datasets over
      the entire body. Data from a single CT acquisition can be reconstructed into
      image series that would formerly have required multiple acquisitions. Small
      isotropic voxels permit scan parameters to be general while reconstruction
      algorithms remain specific to anatomy. While this results in more efficient
      operation in the Emergency Department, it necessitates new ways of displaying,
      interpreting, and archiving the information. Critical decisions include how much
      of the patient to scan and how to time contrast injections when imaging multiple
      organs. These choices must be made in light of dose considerations to the patient
      and the general population of patients. The technical basis of high-density CT
      scanning is discussed, including detector configurations and reconstruction
      techniques. Volumetric scanning in the Emergency Department can improve patient
      care but requires a change of technical habits.

PMID- 20674769
TI  - Spinal cord stimulation: the types of neurostimulation devices currently being
      used, and what radiologists need to know when evaluating their appearance on
      imaging.
AB  - Neural stimulation is increasingly used as a treatment for chronic pain. Common
      indications for spinal cord stimulation include chronic neuropathic and
      oncological pain, intractable angina, or chronic pain secondary to vascular
      disease. It is estimated that up to 4 million patients may be candidates for the
      therapy. Therefore, it is likely that an increasing number of patients will have
      spinal neurostimulation devices implanted over the coming years. Because
      radiography and computed tomography are the primary imaging modalities used to
      evaluate the proper positioning of these devices, radiologists should be familiar
      with their appearance. The purpose of this article is to discuss the types of
      neurostimulation devices currently being used and to demonstrate their respective
      imaging appearances.

PMID- 20674770
TI  - Prevention of neointima formation by taurine ingestion after carotid balloon
      injury.
AB  - The sulfur-containing amino acid, taurine, has been shown to ameliorate the
      vascular disorders. We examined the effects of taurine ingestion on intimal
      thickening following balloon injury. Balloon injury was induced in the left
      common carotid artery of Wistar rats. Taurine (3% (w/v)) was mixed in the
      drinking water from 2 days prior to, until 14 days after the induction of balloon
      injury. The ratio of intima-to-media was significantly reduced by 26% in the
      taurine-treated rats at 14 days after the induction of injury, which was
      associated with reduced proliferation of the vascular smooth muscle cells (SMCs)
      in both the media and the intima. Attenuation of arterial superoxide production
      by taurine ingestion was evident from the results of both the lucigenin
      chemiluminescence method and in situ detection by dihydroethidium (DHE) staining.
      Moreover, LPS-stimulated TNF-alpha production in the blood cells was decreased in
      the taurine-treated rats. The results of the study showed that taurine suppresses
      neointimal formation in balloon-injured arteries, associated with reduced
      proliferation of the vascular SMCs, which is attributable to the anti-oxidative
      effects of taurine. In addition, the anti-inflammatory effects of taurine
      chloramine produced by neutrophils may be related to reduction in SMC
      proliferation in part.

PMID- 20674773
TI  - A relevant question for site balanced studies relates to the comparative
      predictability of minimization to the alternative of permuted blocks.

PMID- 20674774
TI  - Systems of support to increase colorectal cancer screening and follow-up rates
      (SOS): design, challenges, and baseline characteristics of trial participants.
AB  - BACKGROUND: Screening decreases colorectal cancer (CRC) morbidity and mortality,
      yet remains underutilized. Screening breakdowns arise from lack of uptake and
      failure to follow-up after a positive screening test. OBJECTIVES: Systems of
      support to increase colorectal cancer screening and follow-up (SOS) is a
      randomized trial designed to increase: (1) CRC screening and (2) follow-up of
      positive screening tests. The Chronic Care Model and the Preventive Health Model
      inform study design. METHODS: The setting is a large nonprofit healthcare
      organization. In part-1 study, patients age 50-75 due for CRC screening are
      randomized to one of 4 study conditions. Arm 1 receives usual care. Arm 2
      receives automated support (mailed information about screening choices and fecal
      occult blood tests (FOBT)). Arm 3 receives automated and assisted support (a
      medical assistant telephone call). Arm 4 receives automated, assisted, and care
      management support (a registered nurse provides behavioral activation and
      coordination of care). In part-2, study patients with a positive FOBT or adenomas
      on flexible sigmoidoscopy are randomized to receive either usual care or nurse
      care management. Primary outcomes are: 1) the proportion with CRC screening, 2)
      the proportion with a complete diagnostic evaluation after a positive screening
      test. RESULTS: We sent recruitment letters to 15,414 patients and 4675 were
      randomized. Randomly assigned treatment groups were similar in age, sex, race,
      education, self-reported health, and CRC screening history. CONCLUSIONS: We will
      determine the effectiveness and cost effectiveness of stepped increases in
      systems of support to increase CRC screening and follow-up after a positive
      screening test over 2years.

PMID- 20674775
TI  - The use of mid-trial reviews for design modifications in small scale clinical
      studies.
AB  - Many clinical studies such as those in the areas of toxicology, early phase
      clinical trials and bioequivalence studies use small samples due to the high cost
      of experimentation. These studies test hypotheses based on small samples. These
      small samples result in low power and therefore even if the alternative
      hypotheses may be true the chance of it being rejected is low. The sample size is
      determined in an ad-hoc way and no proper scientific approach is used. Sample
      size calculations for clinical studies are usually conducted to determine the
      total number of patients needed to satisfy a specified power requirement, and
      their validity is dependent on pre-trial knowledge of nuisance parameters and
      distributional and modelling assumptions. Another short coming is that often
      hypotheses are tested without checking the assumptions required by the test. This
      paper looks at design reviews in the context of small samples. It examines
      several design modifications done with a small internal pilot study. In the past
      similar techniques have been applied to large scale studies but its performance
      is yet to be established in small scale clinical studies thus the contribution of
      this paper is in justifying the validity of these techniques for small samples
      too. The methodology is illustrated on an uncontrolled observational toxicology
      study. In this paper simulations will be presented showing that the design
      modifications would not influence the type-I error rate and that these would be
      successful in preserving the power, and the implementation of the design review
      procedure will be described.

PMID- 20674776
TI  - The bright future of Chinese herbal medicine: only after a twisty road.
AB  - This article discusses the fundamental theory and history of Chinese herbal
      medicine (CHM) and points out that a series of problems and debates arise about
      CHM. In order to solve these problems, we need to answer the following three
      questions for the future development of CHM: Is CHM safe? Is CHM effective? Which
      ingredient is effective or noxious? Meanwhile, we need to properly handle the
      relationship between inheritance and innovation during the development of CHM.

PMID- 20674777
TI  - Implementation and experience of a web-based allocation system with Pocock and
      Simon's minimization methods.
AB  - Minimization is a type of dynamic randomization method that is recommended for
      use in clinical trials. However, partly due to its organizational complexity in
      implementation, the utilization of minimization is seldom reported. We developed
      a centralized random allocation system named "MagMin" using Pocock and Simon's
      minimization methods, which has been in use since 2006. To date, 5 clinical
      trials have been randomized using this system, and the other 17 clinical trials
      are still running on this system. An example is introduced in this paper to
      describe the implementation of this system. Problems and countermeasures are also
      discussed.

PMID- 20674778
TI  - Foreword.

PMID- 20674779
TI  - Preface surgical complications.

PMID- 20674780
TI  - Preventing electrosurgical energy-related injuries.
AB  - Electrosurgery is used on a daily basis in the operating room, but it remains
      poorly understood by those using it. In addition, the physics of electrosurgery
      are far more complicated than those of laser. Common belief notwithstanding,
      electrosurgery has an enormous capacity for patient injury if used incorrectly,
      even though technology has markedly reduced the likelihood of patient or surgeon
      injuries. This article is intended to educate the clinician regarding the basis
      of electrosurgery and provide an explanation on how injuries may occur as well as
      how they may be prevented.

PMID- 20674781
TI  - Prevention, diagnosis, and treatment of gynecologic surgical site infections.
AB  - Surgical site infections (SSIs) have a significant effect on patient care and
      medical costs. This article outlines the risks that lead to SSIs and the
      preventive measures, including antimicrobial prophylaxis, which decrease the
      incidence of infection. This article also reviews the diagnosis and treatment of
      gynecologic SSIs.

PMID- 20674782
TI  - Avoiding major vessel injury during laparoscopic instrument insertion.
AB  - Major vessel injuries during laparoscopy most commonly occur during insertion of
      Veress needle and port trocars through the abdominal wall. This article reviews
      methods for avoiding major vessel injury while gaining laparoscopic access,
      including anatomic relationships of abdominal wall landmarks to the major
      retroperitoneal vessels. Methods for periumbilical placement of the Veress needle
      and primary trocar are reviewed in terms of direction and angle of insertion, and
      alternative methods and locations are discussed. Methods for secondary port
      placement are reviewed in terms of direction, depth, and speed of placement.

PMID- 20674783
TI  - Complications of hysteroscopic and uterine resectoscopic surgery.
AB  - Adverse events associated with hysteroscopic procedures are in general rare, but,
      with increasing operative complexity, it is now apparent that they are
      experienced more often. A spectrum of complications exist ranging from those that
      relate to generic components of procedures such as patient positioning and
      anesthesia and analgesia, to a number that are specific to intraluminal
      endoscopic surgery (perforation and injuries to surrounding structures and blood
      vessels). The response of premenopausal women to excessive absorption of nonionic
      fluids deserves special attention. There is also an increasing awareness of
      uncommon but problematic sequelae related to the use of monopolar uterine
      resectoscopes that involve thermal injury to the vulva and vagina. The uterus
      that has previously undergone hysteroscopic surgery can behave in unusual ways,
      at least in premenopausal women who experience menstruation or who become
      pregnant. Better understanding of the mechanisms involved in these adverse
      events, as well as the use or development of several devices, have collectively
      provided the opportunity to perform hysteroscopic and resectoscopic surgery in a
      manner that minimizes risk to the patient.

PMID- 20674784
TI  - Gynecologic surgery and the management of hemorrhage.
AB  - Surgical blood loss of more than 1000 mL or blood loss that requires a blood
      transfusion usually defines intraoperative hemorrhage. Intraoperative hemorrhage
      has been reported in 1% to 2% of hysterectomy studies. Preoperative evaluation of
      the patient can aid surgical planning to help prevent intraoperative hemorrhage
      or prepare for the management of hemorrhage, should it occur. To this effect, the
      medical and medication history and use of alternative medication must be
      gathered. This article discusses the methods of preoperative management of
      anemia, including use of iron, recombinant erythropoietin, and gonadotropin
      releasing hormone agonists. The authors have also reviewed the methods of
      intraoperative and postoperative management of bleeding.

PMID- 20674785
TI  - Understanding errors during laparoscopic surgery.
AB  - Complications may occur during laparoscopic surgery, even with a skilled surgeon
      and under ideal circumstances; human error is inevitable. Videotaped procedures
      from malpractice cases are evaluated to ascertain potential contributing
      cognitive factors, systems errors, equipment issues, and surgeon training.
      Situation awareness and principles derived from aviation crew resource management
      may be adapted to help avoid systems error. The current process of surgical
      training may need to be reconsidered.

PMID- 20674786
TI  - Postoperative neuropathy in gynecologic surgery.
AB  - The development of a postoperative neuropathy is a rare complication that can be
      devastating to the patient. Most cases of postoperative neuropathy are caused by
      improper patient positioning and the incorrect placement of surgical retractors.
      This article presents the nerves that are at greatest risk of injury during
      gynecologic surgery through a series of vignettes. Suggestions for protection of
      each nerve are provided.

PMID- 20674787
TI  - Hollow viscus injury during surgery.
AB  - Reproductive tract surgery carries a risk of injury to the bladder, ureter, and
      gastrointestinal (GI) tract. This is due to several factors including close
      surgical proximity of these organs, disease processes that can distort anatomy,
      delayed mechanical and energy effects, and the inability to directly visualize
      organ surfaces. The purpose of this article is to review strategies to prevent,
      recognize, and repair injury to the GI and urinary tract during gynecologic
      surgery.

PMID- 20674788
TI  - Inheritance of resistance to pyrethroids in Triatoma infestans, the main Chagas
      disease vector in South America.
AB  - An outbreak of pyrethroid resistance was recently detected in Triatoma infestans
      from northern Argentina. To analyze the inheritance of the resistant phenotype,
      we carried out experimental crosses between resistant (R) and susceptible (S)
      strains captured in Argentina during 2005. The R strain was collected from
      sprayed houses in the north of the province of Salta while the S strain was
      collected in the province of Chaco. Both strains were bred in the laboratory for
      reciprocal crosses (F1), intercrosses (F2) and backcrosses (BC). The descendents
      were tested by a standard insecticide resistance bioassay. Resistance ratios were
      1 for S strain, 103.36 for R strain and 18.34 for F1. The regression lines of F1
      generations (R*S and S*R) showed no significant differences and were closer to
      that of the R parents, indicating that inheritance of deltamethrin resistance in
      T. infestans is autosomal and incompletely dominant (D=0.20). Chi-square analysis
      from responses of intercross and backcross progenies rejected the hypothesis of a
      single gene being responsible for resistance. The minimum number of independent
      segregation genes was three, as calculated with Lande's method. The genetic basis
      here described for the resistant phenotype indicate that, under pyrethroid
      selective pressure, the resistant genotypes could be easily spread to susceptible
      insects from resistant individuals, posing a major threat to vectorial control of
      Chagas disease.

PMID- 20674789
TI  - Rodent host cell/Lassa virus interactions: evolution and expression of alpha
      Dystroglycan, LARGE-1 and LARGE-2 genes, with special emphasis on the Mastomys
      genus.
AB  - Arenaviruses are usually rodent-borne viruses that constitute a major threat for
      human health. Among them, Lassa Fever Virus (LFV) occurs in Western Africa where
      it infects hundreds of thousands of people annually. According to the most recent
      surveys, LFV is hosted by one of the multimammate rats, Mastomys natalensis, but
      has never been detected in its sibling and sometimes sympatric species Mastomys
      erythroleucus. This pattern suggests that intrinsic, i.e. genetic properties
      underlie such a drastic epidemiological difference (M. natalensis as a reservoir
      vs. M. erythroleucus as a non-reservoir species). Here we investigate genomic
      differences between these two closely related rodent species by focusing on three
      genes that have recently been described as pivotal for LFV/human cell
      interactions: Dystroglycan (the LFV cellular receptor), LARGE-1 and LARGE-2 (two
      enzymes that are essential to Dystroglycan functioning). For all three genes,
      sequence analyses showed that amino-acid chains undergo extremely strong
      purifying selective pressures, and indicated that no nucleotide (therefore no
      tertiary structure) change can be advocated to explain species-specific
      differences in LFV-cellular mediation. Nevertheless, preliminary studies of
      kidney-specific expression profiles suggested that important species-specific
      differences exist between Mastomys species. Taking into account current knowledge
      about LFV-human cell interactions, our results may point towards a possible role
      for LARGE-1 and LARGE-2 enzymes at the intracellular replication level of the
      virus, rather than at the LFV-host cell receptor binding step.

PMID- 20674790
TI  - Emerging respiratory infections in the 21st century. Preface.

PMID- 20674791
TI  - Emerging bacterial, fungal, and viral respiratory infections in transplantation.
AB  - Kidney, liver, heart, pancreas, lung, and small intestine transplantations are
      viable therapeutic options for patients with end-stage organ failure. Ongoing
      advancements of surgical techniques, immunosuppressive regimens, and
      perioperative management have resulted in improved survival of allograft
      recipients. Despite these refinements, infections still contribute to substantial
      morbidity and mortality, limiting long-term success rates of these procedures.
      This article discusses the emerging bacterial, fungal, and viral respiratory
      infections in transplantation.

PMID- 20674792
TI  - Common and emerging fungal pulmonary infections.
AB  - Fungal pulmonary infections are becoming more prevalent as a consequence of the
      rising prevalence of immunocompromised patients. Besides ubiquitous opportunistic
      fungi such as Aspergillus spp and geographically delimited mycoses, fungi that
      were previously thought to be of uncertain pathogenicity, such as hyaline and
      dematiaceous molds, are increasingly being diagnosed as the causes of invasive
      disease in profoundly immunosuppressed hosts. Overall progress in the clinical
      management of fungal pulmonary infections has been slow compared with other areas
      of infectious diseases. However, recent encouraging advances in fungal
      diagnostics and therapeutics have resulted in improved clinical outcomes,
      particularly in vulnerable patient populations such as solid organ or allogeneic
      hematopoietic stem cell transplant recipients. This article provides an overview
      of endemic mycoses and other emerging fungal pulmonary infections. Recent
      developments in terms of the diagnosis and clinical management of these
      infections are also discussed.

PMID- 20674793
TI  - Emerging and established parasitic lung infestations.
AB  - Many lung infestations from established and newly emerging parasites have been
      reported as a result of the emergence of HIV/AIDS, the increasing use of
      immunosuppressive drugs, increasing organ transplantations, the increase in
      global travel, and climate change. A renewed interest in parasitic lung
      infections has been observed recently because many protozoal and helminthic
      parasites cause clinically significant lung diseases. The diseases caused by
      these parasites may mimic common and complicated lung diseases ranging from
      asymptomatic disease to acute respiratory distress syndrome requiring critical
      care management. The availability of new molecular diagnostic methods and
      antiparasitic drugs enables early diagnosis and prompt treatment to avoid the
      morbidity and mortality associated with these infestations. Good hygiene
      practices, improvement in socioeconomic conditions, vector control measures, and
      consumption of hygienically prepared and properly cooked food are essential to
      reduce the occurrence of parasitic infestations.

PMID- 20674794
TI  - Emerging, novel, and known influenza virus infections in humans.
AB  - Influenza viruses continue to cause yearly epidemics and occasional pandemics in
      humans. In recent years, the threat of a possible influenza pandemic arising from
      the avian influenza A(H5N1) virus has prompted the development of comprehensive
      pandemic preparedness programs in many countries. The recent emergence of the
      pandemic influenza A(H1N1) 2009 virus from the Americas in early 2009, although
      surprising in its geographic and zoonotic origins, has tested these preparedness
      programs and revealed areas in which further work is necessary. Nevertheless, the
      plethora of epidemiologic, diagnostic, mathematical and phylogenetic modeling,
      and investigative methodologies developed since the severe acute respiratory
      syndrome outbreak of 2003 and the subsequent sporadic human cases of avian
      influenza have been applied effectively and rapidly to the emergence of this
      novel pandemic virus. This article summarizes some of the findings from such
      investigations, including recommendations for the management of patients infected
      with this newly emerged pathogen.

PMID- 20674795
TI  - Severe acute respiratory syndrome and coronavirus.
AB  - Severe acute respiratory syndrome (SARS) is a highly infectious disease with a
      significant morbidity and mortality. Respiratory failure is the major
      complication, and patients may progress to acute respiratory distress syndrome.
      Health care workers are particularly vulnerable to SARS. SARS has the potential
      of being converted from droplet to airborne transmission. There is currently no
      proven effective treatment of SARS, so early recognition, isolation, and
      stringent infection control are the key to controlling this highly contagious
      disease. Horseshoe bats are implicated in the emergence of novel coronavirus
      infection in humans. Further studies are needed to examine host genetic markers
      that may predict clinical outcome.

PMID- 20674796
TI  - Respiratory infections due to drug-resistant bacteria.
AB  - Pneumonia is the most common infection that is the leading cause of death. The
      increasing antimicrobial resistance in major respiratory pathogens such as
      Streptococcus pneumoniae, Staphylococcus aureus and gram-negative bacteria has
      severely restricted the treatment options. Respiratory infections caused by
      multidrug-resistant bacteria are associated with a greater likelihood of
      inappropriate antimicrobial therapy and poor clinical outcome. Especially,
      treatment of infections caused by pandrug-resistant gram-negative bacteria is a
      major challenge. Continuous efforts to control the global spread of drug
      resistant bacteria are essential.

PMID- 20674797
TI  - Occupation-related respiratory infections revisited.
AB  - Occupational pulmonary infectious diseases include tuberculosis (TB) and many
      viral pathogens, including influenza, coronavirus (severe acute respiratory
      syndrome or SARS), varicella, respiratory syncytial virus, and hantavirus. This
      review focuses on TB, influenza, and SARS, because the published literature is
      extensive for these 3 infections. The lessons from these 3 are relevant for all
      nosocomial pulmonary infectious diseases.

PMID- 20674798
TI  - Pulmonary infectious complications of tumor necrosis factor blockade.
AB  - The understanding of the infection risks posed by tumor necrosis factor (TNF)
      antagonists has continued to evolve in the 10 years since these drugs first were
      introduced. Recent prospective studies have confirmed the risk of tuberculosis
      (TB) reactivation posed by TNF antibodies to be several fold greater than soluble
      TNF receptor. Certolizumab pegol, a monovalent anti-TNF Fab' fragment, appears to
      share this risk, despite its lack of Fc and its inability to cross-link
      transmembrane TNF or activate complement. Two-step (boosted) tuberculin skin test
      screening and initiation of treatment for latent TB infection can greatly reduce
      the TB risk of anti-TNF treatment in western countries. Current recommendations
      for withdrawal of anti-TNF therapy when TB is diagnosed place patients at risk
      for paradoxical worsening due to recovery of TNF-dependent inflammation. Further
      research is needed to determine how best to prevent and manage their infectious
      complications and to determine their potential adjunctive therapeutic role in
      chronic infectious diseases.

PMID- 20674800
TI  - Extensively drug-resistant tuberculosis: epidemiology and management challenges.
AB  - Widespread global use of rifampin for 2 decades preceded the emergence of
      clinically significant multidrug-resistant tuberculosis (MDR-TB) in the early
      1990s. The prevalence of MDR-TB has gradually increased such that it accounts for
      approximately 5% of the global case burden of disease (approximately half a
      million cases in 2007). Eclipsing this worrying trend is the widespread emergence
      of extensively drug-resistant TB (XDR-TB). This article reviews the insights
      provided by clinical and molecular epidemiology regarding global trends and
      transmission dynamics of XDR-TB, and the challenges clinicians have to face in
      diagnosing and managing cases of XDR-TB. The ethical and management dilemmas
      posed by recurrent defaulters, XDR-TB treatment failures, and isolation of
      incurable patients are also discussed. Given the past global trends in MDR-TB, if
      aggressive preventive and management strategies are not implemented, XDR-TB has
      the potential to severely cripple global control efforts of TB.

PMID- 20674799
TI  - The convergence of the global smoking, COPD, tuberculosis, HIV, and respiratory
      infection epidemics.
AB  - At the beginning of the 21st century, we are facing the convergence of several
      epidemics. These include tobacco smoking, tuberculosis, HIV infection, influenza,
      and chronic obstructive pulmonary disease. These epidemics interact by way of
      increasing disease susceptibility and worsening outcomes. To control these
      interacting epidemics, we need to better understand each infection and how it
      influences the others. Multifaceted approaches will be necessary to reduce the
      impact on those in developing nations most likely to be affected by the
      convergence of all epidemics.

PMID- 20674801
TI  - Childhood tuberculosis: an emerging and previously neglected problem.
AB  - Although awareness is growing, childhood tuberculosis (TB) remains a neglected
      disease in many resource-limited settings. In part this reflects operational
      difficulties, lack of visibility in official reports, as well as perceptions that
      children tend to develop mild disease, contribute little to disease transmission,
      and do not affect epidemic control. At an international level there is greater
      appreciation that children contribute significantly to the global TB disease
      burden and suffer severe TB-related morbidity and mortality, particularly in TB
      endemic areas, where the disease often remains undiagnosed. However, this is not
      always the case at the national or local level and there remains an urgent need
      for feasible and implementable policies to guide clinical practice. Pediatric TB
      can be regarded as an emerging epidemic in areas where the adult epidemic remains
      out of control and Mycobacterium tuberculosis transmission is ongoing. This
      article reviews important concepts, challenges, and management principles related
      to childhood TB; it also summarizes the main priorities for future research.

PMID- 20674802
TI  - Tuberculosis in the global aging population.
AB  - Despite the decline in the overall incidence of tuberculosis (TB) in many
      developed countries, it remains an important problem among the older population.
      The control of TB in the elderly remains a major challenge because of the
      limitations of the existing tools for the diagnosis and treatment of latent TB
      infection and clinically active disease. This article examines the current and
      possible future status of TB in the elderly, focusing on epidemiology, risk
      factors, preventive treatment strategies, and clinical disease.

PMID- 20674803
TI  - Nontuberculous mycobacterial lung diseases.
AB  - Nontuberculous mycobacteria (NTM) are generally hardy, ubiquitous environmental
      bacteria that vary in geographic distribution and pulmonary pathogenicity.
      Relatively few of the more than 115 species of NTM have been associated with lung
      disease. Diagnosis of disease due to NTM relies on a combination of clinical,
      imaging, and microbiologic data. Because NTM may present as acid-fast bacilli in
      respiratory secretions of patients with clinical and radiologic features that
      mimic tuberculosis, laboratory discrimination of NTM from Mycobacterium
      tuberculosis is a priority. This discrimination is now often rapidly achievable
      using molecular techniques, although some tests have limited sensitivity. NTM
      species have different antibiotic response patterns, and success with medical
      treatment alone varies. Macrolides are an essential component of therapy for many
      species but must be combined with other drugs.

PMID- 20674804
TI  - Emerging advances in rapid diagnostics of respiratory infections.
AB  - Recent developments in rapid diagnostics for respiratory infections have mostly
      occurred in the areas of antigen and nucleic acid detection. Nucleic acid
      amplification tests have improved the ability to identify respiratory viruses in
      clinical specimens and have played pivotal roles in the rapid characterization of
      new viral pathogens. Antigen-detection assays in immunochromatographic or similar
      formats are most easily developed as near-patient tests, although they have been
      developed commercially only for a limited range of respiratory pathogens. New
      approaches for respiratory pathogen detection are needed, and breath analysis is
      an exciting area with enormous potential.

PMID- 20674805
TI  - Antiviral drug resistance: mechanisms and clinical implications.
AB  - Antiviral drug resistance is an increasing concern in immunocompromised patient
      populations, where ongoing viral replication and prolonged drug exposure lead to
      the selection of resistant strains. Rapid diagnosis of resistance can be made by
      associating characteristic viral mutations with resistance to various drugs as
      determined by phenotypic assays. Management of drug resistance includes
      optimization of host factors and drug delivery, selection of alternative
      therapies based on knowledge of mechanisms of resistance, and the development of
      new antivirals. This article discusses drug resistance in herpesviruses and
      hepatitis B.

PMID- 20674806
TI  - Is augmented central respiratory-sympathetic coupling involved in the generation
      of hypertension?
AB  - Respiratory modulation of autonomic neural activity, with consequent phasic
      alteration of cardiac and vascular function, has been observed in many species
      including humans and is considered an index of cardiovascular health. Whilst many
      factors contribute to this modulation, including for example baroreceptor reflex
      feedback, it is accepted that a significant component is derived from an
      interaction within the central nervous system. Functional links between the
      brainstem circuitry generating the respiratory rhythm and neurons responsible for
      generate sympathetic and parasympathetic activity to the cardiovascular system
      have long been hypothesized, although the detailed understanding of these
      interactions is incomplete. There are several proposed physiological functions
      for these interactions including the matching of ventilation to cardiac output
      and tissue blood flow. However, recent observations suggest that altered central
      respiratory coupling may play a role in the development of hypertension and in
      the maintenance of elevated levels of sympathetic vasomotor activity in disease.
      The focus of this review article is to discuss these observations and place them
      within the context of current understanding of the neural substrates that might
      be responsible for respiratory-sympathetic coupling.

PMID- 20674807
TI  - The effects of baroreceptor stimulation on central respiratory drive: a review.
AB  - The neural systems that control breathing and the circulation are located in
      adjacent longitudinal columns in the ventrolateral medulla. They have much in
      common, in terms of their structure, function, and evolution. In the most part,
      both systems are affected by the same sensory modalities and receive input from
      many of the same higher centres. Indeed, such is the parallel organisation of the
      two systems that stimuli that alter the behaviour of the one almost invariably
      influence the other. It is well-known that rhythmic respiratory inputs exert
      powerful effects on parasympathetic and sympathetic outputs. However, the
      question of whether cardiovascular inputs exert any influence on respiratory
      rhythmogenesis is more contentious. Here, we review the effects of baroreceptor
      activation, classically considered a 'cardiovascular' stimulus, on respiratory
      drive. We show that, although subtle, baroreceptor inputs evoke reproducible
      prolongation of expiration in a range of preparations. The consequences of this
      reflex are discussed with regard to cardiorespiratory coordination.

PMID- 20674808
TI  - Phenotypic changes in bone marrow-derived murine macrophages cultured on PEG
      based hydrogels activated or not by lipopolysaccharide.
AB  - Macrophages are phenotypically diverse cells performing a number of functions
      involved in immunity, inflammation, wound healing, tissue homeostasis and the
      foreign body reaction. In the latter, the type of biomaterial and the surrounding
      environment likely have an impact on macrophage phenotype and, subsequently, the
      severity of the reaction. The objectives for this study were to characterize the
      phenotype of bone marrow-derived murine macrophages in response to poly(ethylene
      glycol) (PEG)-based hydrogels, a promising class of materials for cell delivery.
      Gene expression was used as a measure of phenotype and characterized by IL-1beta,
      TNF-alpha, iNOS, IL-12beta, arginase, VEGF-A, and IL-10. Macrophages were
      cultured on PEG hydrogels, PEG hydrogels with RGD tethers, and medical grade
      silicone rubber, a well-characterized biomaterial, up to 96 h in the absence and
      presence of lipopolysaccharide (LPS) to simulate an inflammatory environment.
      Macrophage interrogation led to immediate up-regulation (10*) of IL-1beta and TNF
      alpha within 4h, followed by an increase in IL-10/IL-12beta and a subsequent
      concomitant decrease in the pro-inflammatory genes by 96 h, suggesting a shift
      from classically activated to a regulatory phenotype. LPS stimulation led to a
      stronger early up-regulation of pro-inflammatory genes (e.g. 20-30* for IL-1beta
      and TNF-alpha), followed by upregulation (4-6*) of arginase, suggesting a shift
      from an elevated classically activated to a wound healing phenotype. Material
      type played a significant role in regulating pro-inflammatory genes, which was
      most pronounced with PEG alone. Overall, our findings indicate that macrophages
      undergo similar phenotypic changes for the materials tested, but the magnitudes
      of these responses are highly material dependent.

PMID- 20674809
TI  - Phospholipid bilayer formation on a variety of nanoporous oxide and organic
      xerogel films.
AB  - Lipid bilayers supported by nanoporous xerogel materials are being explored as
      models for cell membranes. In order to better understand and characterize the
      nature of the surface-bilayer interactions, several oxide and organic nanoporous
      xerogel films (alumina, titania, iron oxide, phloroglucinol-formaldehyde,
      resorcinol-formaldehyde and cellulose acetate) have been investigated as a
      scaffold for vesicle-fused 1,2-dioleoyl-glycero-3-phosphocholine (DOPC) lipid
      bilayer formation and mobility. The surface topography of the different
      substrates was analyzed using contact and tapping-mode atomic force microscopy
      and the surface energy of the substrates was determined using contact angle
      goniometry. Lipid bilayer formation has been observed with fluorescence
      microscopy and lateral lipid diffusion coefficients have been determined using
      fluorescence recovery after photobleaching. Titania xerogel films were found to
      be a robust and convenient support for formation of a two-phase DOPC/1,2
      distearoyl-glycero-3-phosphocholine bilayer and domains were observed with this
      system. It was found that the cellulose acetate xerogel film support produced the
      slowest lipid lateral diffusion.

PMID- 20674810
TI  - Abdominal nodal localization of Castleman's disease: report of a case.
AB  - INTRODUCTION: Castleman's disease (CD) is a rare benign disorder that may grow in
      any area where lymphoid tissue is normally present but the most frequent site is
      mediastinum (67%); the abdomen is rarely affected by this pathology. In the
      pathogenesis of CD an important role could be played by HHV-8. Diagnosis is
      difficult and the diagnostic certainty is obtained only by histological
      examination. For this disease there is no gold-standard treatment. CASE REPORT:
      We report the case of a woman of 33 years of age affected by a rare form of
      abdominal nodal localization of Castleman's Disease for which the patient
      underwent surgery. CONCLUSION: CD must be included in the differential diagnosis
      of retroperitoneal tumors even though the definitive diagnosis can only be
      achieved by histological and immunohistochemical examination. In the case of
      single location, the treatment of choice is surgical removal.

PMID- 20674811
TI  - Predictive factors for successful early laparoscopic cholecystectomy in acute
      cholecystitis: a prospective study.
AB  - BACKGROUND: Early laparoscopic cholecystectomy has become the treatment of choice
      for acute cholecystitis. However, the rate of intraoperative conversion to open
      surgery remains high and has provoked an interest in studying the predictive
      factors for better patient selection to minimize the conversion rates. MATERIALS
      AND METHODS: 50 patients of acute cholecystitis were operated within 5 days of
      onset of symptoms. Comparative evaluation of the patient groups undergoing
      successful versus failed early laparoscopic cholecystectomy was done to identify
      preoperative factors predicting conversion/failure of the laparoscopic procedure.
      Predictive factors for intraoperative and histopathological severity of acute
      cholecystitis were also identified. RESULTS: 40 patients underwent successful
      completion of early laparoscopic cholecystectomy, 8 required conversions to open,
      while in 2 patients the procedure had to be abandoned due to phlegmon formation.
      Male sex, preoperative duration of symptoms WBC counts, serum alkaline
      phosphatase, serum amylase, and serum C-reactive protein were significant
      predictors of histopathological severity of acute cholecystitis. Intraoperative
      and histopathological severity of acute cholecystitis had good association with
      conversion rate of early laparoscopic cholecystectomy. Male sex and serum C
      reactive protein levels >3.6 mg/dl at admission were very strong predictors of
      conversion/failure of early laparoscopic cholecystectomy in acute cholecystitis.
      CONCLUSION: Male patients of acute cholecystitis or patient with serum C-reactive
      protein levels of >3.6 mg/dl at admission have high risk of conversion in early
      laparoscopic cholecystectomy and warrant a conservative early management followed
      by delayed laparoscopic cholecystectomy.

PMID- 20674812
TI  - Selection and characterisation of affibody molecules inhibiting the interaction
      between Ras and Raf in vitro.
AB  - Development of molecules with the ability to selectively inhibit particular
      protein-protein interactions is important in providing tools for understanding
      cell biology. In this work, we describe efforts to select small Ras- and Raf
      specific three-helix bundle affibody binding proteins capable of inhibiting the
      interaction between H-Ras and Raf-1, from a combinatorial library displayed on
      bacteriophage. Target-specific variants with typically high nanomolar or low
      micromolar affinities (K(D)) could be selected successfully against both
      proteins, as shown by dot blot, ELISA and real-time biospecific interaction
      analyses. Affibody molecule variants selected against H-Ras were shown to bind
      epitopes overlapping each other at a site that differed from that at which H-Ras
      interacts with Raf-1. In contrast, an affibody molecule isolated during selection
      against Raf-1 was shown to effectively inhibit the interaction between H-Ras and
      Raf-1 in a dose-dependent manner. Possible intracellular applications of the
      selected affibody molecules are discussed.

PMID- 20674813
TI  - Ubiquitin-proteasome system and mitochondria - reciprocity.
AB  - Recently, sporadic links have been published between mitochondria - membrane
      confined organelles - and the cytosolic ubiquitin-proteasome system (UPS) for
      removal of cellular proteins. For example, Fzo1, a mitochondrial outer membrane
      mitofusin was shown to be ubiquitinated by a ubiquitin ligase, Cdc53(MDM30), and
      degraded by the proteasome. Two additional ubiquitin ligases, MITOL/MARCH-V and
      MULAN, as well as a deubiquitinating enzyme, Ubp16/USP30, are embedded in
      mitochondrial outer membranes and participate in mitochondrial dynamics. Defects
      in mitochondrial morphology or respiration capacity are also reported for
      mutations in other UPS components such as the Ub ligases Parkin and Rsp5 as well
      as in proteasome subunits. These examples are likely to reflect a pervasive
      involvement of UPS in recycling of mitochondria-associated proteins. The flux of
      imported proteins and the proximity to oxidative phosphorylation results in
      abundant damaged or misfolded proteins that generate the need for a responsive
      quality control system. Within the mitochondrial matrix there is a self-contained
      ATP-dependent system for protein turnover. However at the outer membrane, the UPS
      may play a corresponding role in recycling either membrane-embedded or imported
      proteins. In a parallel process, ubiquitination also partakes in selection of
      damaged mitochondria to the lysozome/vacuole via autophagy. In the reverse
      direction, components of the UPS are sensitive to cellular REDOX potential, and
      as such are affected by reactive oxygen species (ROS) generated as a byproduct of
      mitochondrial respiration. This review will try to address the regulation of
      mitochondrial morphology and metabolic function by UPS, as well as the reciprocal
      relationship between aberrant ROS produced by mitochondria and ubiquitination or
      proteasome activity. This article is part of a Special Issue entitled The 26S
      Proteasome: When degradation is just not enough!

PMID- 20674815
TI  - [Dreaming is a hypnic state of consciousness: getting rid of the Goblot
      hypothesis and its modern avatars].
AB  - SUMMARY: In the late nineteenth century, French logician Edmond Goblot first
      hypothesized that dreaming occurred at the moment of awakening only. Revisiting-
      more or less directly--Goblot's hypothesis, several contemporary authors have
      since renewed this unusual claim that oniric experience does not occur during
      sleep. So did some influential analytical philosophers (Wittgenstein, Malcolm,
      Dennett), with their typical formalism, and famous dream researcher Calvin Hall,
      who tried to provide experimental evidence for the Goblot's hypothesis. More
      recently, French neurobiologist Jean-Pol Tassin claimed, on the basis of
      controversial neurobiological and cognitive principles, that only awakening gives
      rise to a dream, by instantaneous shaping of information issuing of neural
      networks activated during preceding sleep. Actually, numerous and robust
      experimental data in sleep psychophysiology clearly rule out Goblot's hypothesis
      and its modern avatars. Thus, results of studies using nocturnal awakenings (with
      or without preceding hypnic stimulation), as well as observations of onirical
      behaviours (like rapid eye movement sleep behavior disorders, or voluntary
      movements of lucid dreamers) demonstrate that dreaming definitely occurs during
      sleep. Actually, cortical evoked potentials can be observed during sleep, which
      likely reflect controlled cognitive processes. Dreaming is a hypnic state of
      consciousness, and seems to represent a sleep thought which, although uneasily
      accessible, is nevertheless open to psychological investigation.

PMID- 20674816
TI  - Excitability of the lower-limb area of the motor cortex in Parkinson's disease.
AB  - SUMMARY OBJECTIVE: The excitability of the lower-limb area of the motor cortex
      was investigated in patients with Parkinson's disease (PD) and in control
      subjects. Our results were compared to literature data assessing upper-limb
      cortical area. We analysed the effect of dopaminergic substitution therapy (DST).
      METHODS: Motor evoked potential (MEP) were assessed with transcranial magnetic
      stimulation (TMS) in 24 PD patients with (ON) and without (OFF) DST, and nine age
      matched controls. RESULTS: Resting motor threshold (RMT), active motor threshold
      (AMT), cortical silent period (CSP), MEP amplitude and area did not differ
      significantly between groups and medication states. A paired-pulse TMS study
      revealed normal short-interval intracortical inhibition (SICI) but impaired
      intracortical facilitation (ICF) in PD OFF, partially normalized under DST. Post
      hoc analysis uncovered two opposite effects of DST on MEP amplitude, separating
      the population in two groups. The paired-pulse study confirmed this division,
      showing that both groups exhibited distinct intracortical functioning, which was
      differently influenced by DST. CONCLUSIONS: The lower-limb motor cortical areas
      of PD patients essentially exhibited an ICF reduction whereas in upper-limb
      areas, literature data demonstrated impairment of both SICI and ICF. Our data
      revealed two groups of patients showing different excitability states and
      opposite responses to DST. SIGNIFICANCE: The defective ICF in lower-limb areas
      could play a key role in the pathophysiology of gait disorders in PD. The fact
      that two cortical excitability states are inversely influenced by DST may reflect
      different conditions of denervation and compensatory mechanisms progression.

PMID- 20674814
TI  - Role of ubiquitin-proteasome-mediated proteolysis in nervous system disease.
AB  - Proteolysis by the ubiquitin-proteasome pathway (UPP) is now widely recognized as
      a molecular mechanism controlling myriad normal functions in the nervous system.
      Also, this pathway is intimately linked to many diseases and disorders of the
      brain. Among the diseases connected to the UPP are neurodegenerative disorders
      such as Alzheimer's, Parkinson's and Huntington's diseases. Perturbation in the
      UPP is also believed to play a causative role in mental disorders such as
      Angelman syndrome. The pathology of neurodegenerative diseases is characterized
      by abnormal deposition of insoluble protein aggregates or inclusion bodies within
      neurons. The ubiquitinated protein aggregates are believed to result from
      dysfunction of the UPP or from structural changes in the protein substrates which
      prevent their recognition and degradation by the UPP. An early effect of abnormal
      UPP in diseases of the nervous system is likely to be impairment of synaptic
      function. Here we discuss the UPP and its physiological roles in the nervous
      system and how alterations in the UPP relate to development of nervous system
      diseases. This article is part of a Special Issue entitled The 26S Proteasome:
      When degradation is just not enough!

PMID- 20674817
TI  - Preanalytical factors and reference values in posturographic studies. Much
      remains to be done and explored.

PMID- 20674819
TI  - From atopic dermatitis to asthma: the atopic march.
AB  - OBJECTIVE: To examine the mechanisms whereby allergen exposure through the
      epidermis could initiate systemic allergy and predispose individuals to the
      development of 1 or more atopic diseases via the so-called atopic march. DATA
      SOURCES: PubMed databases from 1950 to the present were searched for relevant
      articles pertaining to epidemiologic and genetic evidence of the progression of
      the atopic march. STUDY SELECTION: Articles concerning pathophysiologic
      conditions that link atopic dermatitis, allergic rhinitis, and asthma were
      examined. RESULTS: The data suggest that a sequence of atopic manifestations
      occurs, typically atopic dermatitis in infancy followed by allergic rhinitis
      and/or asthma in later stages. Reduced filaggrin expression is implicated as a
      major predisposing factor for atopy in multiple lines of evidence, including
      genome-wide analysis and microarray investigations. Other gene products have an
      important role. Cross-sectional and longitudinal studies provide preliminary
      epidemiologic support for the sequential development of allergic diseases.
      CONCLUSION: The mechanisms by which allergen exposure through the epidermis can
      initiate systemic allergy and predispose individuals to atopic dermatitis,
      allergic rhinitis, and asthma have become clearer in recent years. Longitudinal
      studies of individuals carrying loss-of-function filaggrin gene mutations are
      needed to further define the risks associated with epidermal barrier dysfunction
      and potentially identify specific targets for barrier repair and prevention of
      atopic dermatitis and other atopic disease. The effects of preventive and
      treatment strategies have been inconsistent across studies, and further research
      is warranted before any definitive recommendations can be made.

PMID- 20674821
TI  - Impact of asthma control on sleep, attendance at work, normal activities, and
      disease burden.
AB  - BACKGROUND: The 2007 Expert Panel Report 3 asthma treatment guidelines place
      substantial emphasis on understanding the effectiveness of treatment strategies
      on outcomes such as disease control. OBJECTIVE: To assess the impact of asthma
      control on patient-reported outcomes and disease burden in a real-world setting.
      METHODS: Patients aged 18 to 64 years with moderate to severe asthma defined by
      medical and pharmaceutical use were asked to participate in a cross-sectional
      survey of asthma care, control, and burden. Patients were included if they had an
      International Classification of Diseases, Ninth Revision, Clinical Modification
      code for asthma, a prescription for an Expert Panel Report 3-defined controller
      medication (or combinations), and 24-month pre-index continuous eligibility.
      Patients with chronic obstructive pulmonary disease were excluded. Survey
      respondent data were linked to commercial health claims information to create the
      research database. The Asthma Therapy Assessment Questionnaire (ATAQ) was used as
      the measure of control. The ATAQ scores range from 0 to 4, with 0 indicating no
      asthma control problems. RESULTS: A total of 1,199 patients (73% women) completed
      the survey and had their claims data linked for analysis. Age, sex, and
      comorbidity index measures did not differ between respondents and nonrespondents.
      Only 12.2% of respondents scored 0 on the ATAQ, 77.0% scored 1 or 2, and 10.8%
      scored 3 or 4. The ATAQ scores were moderately correlated with patient-rated
      severity. Decreasing levels of asthma control were associated with greater
      prevalences of sleep problems, depression, functional impairment, and effect on
      work and regular activities. CONCLUSIONS: Approximately 88% of patients with
      moderate to severe asthma were not fully controlled despite anti-inflammatory
      drug treatment. Lack of asthma control is associated with substantial patient
      burden.

PMID- 20674820
TI  - Asthma in pregnancy and its pharmacologic treatment.
AB  - BACKGROUND: Asthma is among the most common serious medical problems in
      pregnancy, and its prevalence may be increasing. Management is problematic
      because asthma may harm the fetus, yet little is known about fetal risks of
      asthma medications. OBJECTIVE: To examine the prevalence, symptom control, and
      pharmacologic treatment of asthma in pregnancy. METHODS: Study participants were
      a random sample of 3,609 mothers of nonmalformed infants born in Massachusetts
      between 1998 and 2006. Interviewed within 6 months of delivery, participants were
      asked specific asthma-related questions and classified as having physician
      diagnosed, possible, past, or no asthma; those with physician-diagnosed asthma
      were classified as having well-controlled, not well-controlled, or poorly
      controlled asthma. Drug treatments were grouped into corticosteroids, beta(2)
      agonists, leukotriene modifiers, combination products, and others. RESULTS:
      Physician-diagnosed asthma was present in 502 women (13.9%) and possible asthma
      in an additional 578(16.0%). Higher rates of asthma were observed among women who
      were younger, white, obese, and less well educated, had lower income, and smoked
      during pregnancy. Secular changes were unremarkable: leukotriene modifiers were
      used by only 3.4% of asthmatic women; inhaled steroid use increased only from
      19.0% during 1997-1999 to 23.3% in 2003-2005, whereas use of inhaled beta(2)
      agonists exceeded 50% in both periods. Less than 40% of women with poorly
      controlled asthma symptoms reported use of a controller medication. CONCLUSIONS:
      High rates of asthma and asthma symptoms, together with the low rates of use of
      controller medications, underscore the need to better understand the risks and
      safety of asthma medications during pregnancy.

PMID- 20674822
TI  - GSTM1, GSTP1, prenatal smoke exposure, and atopic dermatitis.
AB  - BACKGROUND: The increase in the prevalence of atopic dermatitis (AD) is likely to
      involve changes in specific environmental exposures among genetically susceptible
      individuals. OBJECTIVE: To evaluate the effect of glutathione S-transferase (GST)
      genotype polymorphisms and prenatal smoke exposure on pediatric AD on the basis
      of the cord blood cotinine levels. METHODS: We conducted a case-control study
      composed of 34 children with AD and 106 non-AD controls, all of whom were
      selected from 483 participants in the Taiwan Birth Panel cohort study. Cord blood
      samples and information on perinatal factors of children were gathered at birth.
      At 2 years of age, information about the development of AD and environmental
      exposures was collected. We compared AD with non-AD children for GTM1 and GSTP1
      polymorphisms stratified by the cotinine level. Multiple logistic regressions
      were performed to estimate the association of genotype polymorphisms and cotinine
      levels with AD. RESULTS: GSTM1 null and GSTP1 Ile/Ile genotypes showed a
      significant increase in the risk of AD (odds ratio [OR], 3.61; 95% confidence
      interval [CI], 1.40-9.31; and OR, 3.11; 95% CI, 1.30-7.46; respectively). In
      children with a cotinine level less than 0.1 ng/mL, the risk of AD increased for
      those carrying 2 GSTP1 Ile-105 alleles (OR, 6.63; 95% CI, 1.46-30.18). In
      children a with cotinine level of 0.1 ng/mL or greater, the GSTM1 null genotype
      was significantly related to AD (OR, 5.21; 95% CI, 1.32-20.58). CONCLUSIONS:
      Within groups of children, genetic polymorphisms in GSTM1 and GSTP1 may be
      responsible for differences in susceptibility to AD with regard to prenatal smoke
      exposure.

PMID- 20674823
TI  - Use of intranasal ketorolac and modified oral aspirin challenge for
      desensitization of aspirin-exacerbated respiratory disease.
AB  - BACKGROUND: Intranasal ketorolac challenges can induce respiratory reactions in
      patients with aspirin-exacerbated respiratory disease (AERD). OBJECTIVE: To
      determine whether intranasal ketorolac challenges might be used for aspirin
      desensitization. METHODS: One hundred patients with suspected AERD who were
      referred to Scripps Clinic from May 1, 2007 to December 31, 2009 were challenged
      with 4 increasing doses of ketorolac intranasally at 30-minute intervals.
      Symptoms, objective changes in the results of their nasal examination, peak nasal
      inspiratory flow rates, and forced expiratory volume in 1 second (FEV(1)) values
      were recorded. After nasal ketorolac dosing, patients were given oral aspirin as
      part of the challenge and desensitization. A control group consisted of 100
      patients who had previously undergone our standard oral aspirin challenges and
      desensitization. Both groups were consecutively enrolled and had similar clinical
      characteristics. RESULTS: Compared with the standard oral aspirin challenge and
      desensitization, intranasal ketorolac and modified aspirin challenge
      significantly attenuated the mean percentage decrease in FEV(1) values (8.5% vs
      13.4%; P = .01) and decreased the percentage of extrapulmonary reactions (23% vs
      45%; P = .002), particularly laryngospasm (7% vs19%; P = .02) and
      gastrointestinal reactions (12% vs 33%; P = .001). This new protocol was
      significantly shorter, lasting an average of 1.9 vs 2.6 days (P = <.001). In
      fact, 83% of the patients completed the new protocol in less than 48 hours
      compared with only 20% in the oral challenge control group (P < .001).
      CONCLUSIONS: Intranasal ketorolac challenge and desensitization followed by rapid
      oral aspirin challenges is effective, safe, and less time-consuming than our
      standard oral aspirin desensitization protocol.

PMID- 20674824
TI  - Use of commercial anti-penicillin IgE fluorometric enzyme immunoassays to
      diagnose penicillin allergy.
AB  - BACKGROUND: The intermittent unavailability of penicilloyl-polylysine since
      September 2000 has focused interest on commercial anti-penicillin IgE
      fluorometric enzyme immunoassay (FEIA) tests to evaluate penicillin allergy.
      There has been no published comparison of commercial anti-penicillin IgE FEIAs
      and penicillin skin testing performed in the United States. OBJECTIVE: To
      determine whether the current commercial anti-penicillin IgE FEIAs can replace or
      augment penicillin skin testing and oral challenges when evaluating individuals
      with a history of penicillin allergy for future therapeutic penicillin tolerance.
      METHODS: A prospective convenience sample of 150 individuals with a history of
      penicillin allergy were evaluated between January 23, 2007, and August 4, 2009,
      with both penicillin skin tests and commercial anti-penicillin IgE FEIAs to
      penicillin G, penicillin V, and amoxicillin. All individuals with a negative
      penicillin skin test result underwent oral penicillin class antibiotic
      challenges. All individuals with a positive anti-penicillin IgE FEIA result also
      underwent oral penicillin class antibiotic challenges. RESULTS: Six individuals
      (4.0%; 95% confidence interval [CI], 0.9% to 7.1%) had positive penicillin skin
      test results, and none had positive FEIA results. Four individuals (2.7%; 95% CI,
      0.1% to 5.3%) had positive FEIA results, and none had positive penicillin skin
      test results. Three individuals (2.0%; 95% CI, -0.2% to 4.2%) had positive oral
      challenge results, 1 with hives at 6 hours after challenge and 2 with delayed
      onset (at >24 hours) nonurticarial rashes, and none had positive FEIA results.
      CONCLUSIONS: The current commercial anti-penicillin IgE FEIAs are not useful in
      diagnosing penicillin allergy in patients with remote histories of penicillin
      allergy. Penicillin skin testing and, if the results are negative, an oral
      challenge remain the criterion standard tests to determine therapeutic penicillin
      tolerance.

PMID- 20674825
TI  - Development of a daily diary for patients with chronic idiopathic urticaria.
AB  - BACKGROUND: Chronic idiopathic urticaria (CIU) is a disease characterized by
      itching and skin hives or wheals of unknown cause that vary in size and last for
      at least 6 weeks. The criterion standard for measuring disease activity is the
      urticaria activity score (UAS). However, content validity of the UAS has not been
      previously reported. OBJECTIVES: To identify outcomes important to patients with
      CIU, create an urticaria patient daily diary based on the UAS and input from
      patients, and assess its content validity. METHODS: A qualitative research study
      was conducted in 2 stages using one-on-one telephone interviews of patients with
      CIU. In stage 1, patients were asked to discuss the impact of CIU on aspects of
      their life and to evaluate the content of the UAS. On the basis of this
      information, a patient daily diary, including UAS items, was developed. In stage
      2, patients were interviewed to determine whether the urticaria patient daily
      diary was comprehensive and easily understood. RESULTS: Stage 1 interviews showed
      that CIU has an extensive impact on patients, from the primary symptoms of
      itching, hives, and angioedema to the broader aspects of sleep and health-related
      quality of life. Stage 2 interviews demonstrated the content validity of the
      urticaria patient daily diary and resulted in minor modifications to the diary.
      When the urticaria patient daily diary was administered in conjunction with the
      Dermatology Life Quality Index and Medical Outcomes Study Sleep Scale, patients
      considered the assessment to be comprehensive, although some recommendations were
      made to include more items on emotional issues and other aspects of angioedema.
      CONCLUSIONS: The final urticaria patient daily diary is an easy-to-administer,
      comprehensive assessment of symptoms for CIU patients. Future research is needed
      to establish its additional psychometric properties.

PMID- 20674826
TI  - Population pharmacokinetics of plasma-derived C1 esterase inhibitor concentrate
      used to treat acute hereditary angioedema attacks.
AB  - BACKGROUND: C1 esterase inhibitor (C1-INH) replacement is recommended as a first
      line therapy for acute edema attacks in hereditary angioedema (HAE). Only limited
      pharmacokinetic analyses of the administered C1-INH in plasma are available.
      OBJECTIVE: To investigate retrospectively the population pharmacokinetics of a
      plasma-derived C1-INH (pC1-INH) concentrate used to treat acute HAE attacks in a
      randomized, placebo-controlled phase 2/3 study in patients with HAE. METHODS:
      Acute abdominal and facial attacks were treated with either a pC1-INH concentrate
      (Berinert) at single intravenous doses of 10 or 20 U/kg body weight or placebo.
      Plasma sampling was conducted 0, 1, and 4 hours after dosing. A nonlinear
      retrospective population pharmacokinetic model was obtained using the assumption
      of a 1-compartment model. RESULTS: The final population pharmacokinetic model was
      based on data from 97 patients treated with 10 or 20 U/kg of pC1-INH concentrate.
      The estimated mean half-life was 32.7 hours (90% confidence interval, 16.6-48.8
      hours), and the estimated mean clearance was 0.92 mL/kg/h (90% confidence
      interval, 0.50-1.33 mL/kg/h). CONCLUSIONS: The half-life of the same pC1-INH
      concentrate reported in a previous study was confirmed by this retrospective
      population pharmacokinetic analysis in patients treated for acute HAE attacks. In
      contrast to other treatment options with shorter half-lives, the long half-life
      of pC1-INH concentrate may provide an extended period of protection, even after
      the symptoms of an attack have subsided.

PMID- 20674827
TI  - Effect of the addition of montelukast to fluticasone propionate for the treatment
      of perennial allergic rhinitis.
AB  - BACKGROUND: Guidelines for the treatment of patients with allergic rhinitis (AR)
      recommend intranasal corticosteroids as first-line therapy. In clinical trials,
      however, only 50% of patients obtain excellent symptom control. OBJECTIVE: To
      evaluate the effectiveness of montelukast add-on therapy in patients with
      perennial AR (PAR) who have incomplete relief of symptoms after 2 weeks of
      treatment with intranasal fluticasone propionate. METHODS: We performed a 4-week
      parallel, randomized, double-blind, placebo-controlled trial. One hundred two
      patients with a history of PAR and a positive skin test reaction to perennial
      allergens were recruited. They completed the Rhinitis Quality of Life
      Questionnaire (RQLQ) and were given intranasal fluticasone propionate, 200 microg
      daily. They were asked to complete symptom diary cards twice daily. After 2 weeks
      of treatment, patients with a mean total nasal symptom score of at least 4 during
      the past week (n = 54) were randomized to receive either montelukast (n = 28) or
      placebo (n = 26) in addition to the continued use of fluticasone propionate. At
      weeks 3 and 4, the RQLQ was completed again and symptom diary cards were
      collected. RESULTS: Compared with baseline, there were significant improvements
      in almost all domains of the RQLQ while taking fluticasone propionate (P < .001).
      A similar trend was observed for nasal symptom scores. After randomization to
      receive montelukast or placebo, there were no significant differences in RQLQ
      measures or nasal symptom scores between the groups during the 2 weeks of
      combination therapy. CONCLUSION: The addition of montelukast to an intranasal
      corticosteroid for the treatment of PAR with residual symptoms is no more
      effective than is placebo.

PMID- 20674828
TI  - Relationship between fractional exhaled nitric oxide and nasal nitric oxide in
      airways disease.
AB  - BACKGROUND: Invasive techniques show evidence of a unified allergic airway.
      Nitric oxide is measured noninvasively from the lungs (fractional exhaled nitric
      oxide [FeNO]) and nose (nasal nitric oxide [nNO]). OBJECTIVE: To investigate the
      relationship between FeNO and nNO in different airway conditions. METHODS: A
      total of 227 participants were assessed: 41 healthy volunteers (HVs), 33 patients
      with asthma, 52 patients with allergic rhinitis (AR), 63 with unified airway
      disease (UAD), and 38 with nasal polyposis (NP). Correlation and multiple linear
      regression analyses were performed. RESULTS: Geometric means (95% confidence
      intervals) for FeNO were as follows: 14.7 (12.4-17.5) ppb for HVs, 29.0 (22.5
      37.4) ppb for asthma patients, 23.1 (19.0-28.1) for AR patients, 27.2 (23.0-32.4)
      for UAD patients, and 28.5 (21.5-37.8) for NP patients. For nNO, the values were
      as follows: 878.1 (807.0-955.6) ppb for HVs, 674.1 (557.4-815.1) for asthma
      patients, 853.3 (778.8-934.8) ppb for AR patients, 763.4 (694.1-839.5) for UAD
      patients, and 388.6 (317.9-474.9) for NP patients. The nNO was lower in the NP
      group than the other groups (P < .001). The nNO and FeNO were correlated in the
      AR patients (r = 0.56; P < .0001) and HVs (r = 0.44; P = .004) but not
      significantly in the other groups. Multiple linear regression of the whole cohort
      demonstrated that after diagnosis, age, sex, and inhaled corticosteroids were
      taken into account nNO had a significant association with FeNO (P = .02).
      CONCLUSION: Reduced nNO in NP patients is due to ostiomeatal complex obstruction.
      FeNO is sensitive to suppression by inhaled corticosteroids. The AR and HV groups
      have no such confounders; hence, correlation is most evident. Exclusion of
      confounders reveals a correlation between upper and lower airway inflammation
      with noninvasive techniques.

PMID- 20674829
TI  - Double-blind, placebo-controlled study of azelastine and fluticasone in a single
      nasal spray delivery device.
AB  - BACKGROUND: A proof-of-concept study suggested that combination therapy with
      commercial azelastine hydrochloride nasal spray and fluticasone propionate nasal
      spray significantly improved nasal symptoms of seasonal allergic rhinitis
      compared with either agent alone. OBJECTIVE: To compare an azelastine-fluticasone
      combination nasal spray administered in a single-delivery device with a
      commercially available azelastine nasal spray and fluticasone nasal spray.
      METHODS: This 14-day, multicenter, randomized, double-blind study was conducted
      during the Texas mountain cedar season. After a 5-day placebo lead-in, 610
      patients with moderate-to-severe nasal symptoms were randomized to treatment with
      (1) azelastine nasal spray, (2) fluticasone nasal spray, (3) combination
      azelastine and fluticasone nasal spray, or (4) placebo nasal spray. All
      treatments were given as 1 spray per nostril twice daily. The primary efficacy
      variable was the change from baseline in the total nasal symptom score (TNSS),
      consisting of nasal congestion, runny nose, itchy nose, and sneezing. RESULTS:
      All 3 active groups were statistically superior (P <or= .02) to placebo, and the
      combination was statistically superior (P <or= .003) to either agent alone. The
      TNSS improved by 28.4% with combination azelastine-fluticasone, 20.4% with
      fluticasone, 16.4% with azelastine, and 11.2% with placebo. All 3 treatments were
      well tolerated. CONCLUSIONS: The combination azelastine-fluticasone nasal spray
      provided statistically significant improvement in the TNSS and additive clinical
      benefit compared with either agent alone in patients with moderate-to-severe
      seasonal allergic rhinitis. TRIAL REGISTRATION: clinicaltrials.gov Identifier:
      NCT00660517.

PMID- 20674830
TI  - The Back to School asthma study: the effect of montelukast on asthma burden when
      initiated prophylactically at the start of the school year.
AB  - BACKGROUND: Pediatric asthma hospitalizations peak in early autumn. OBJECTIVE: To
      determine the effectiveness of montelukast therapy in reducing the asthma burden
      in children when initiated prophylactically on school return. METHODS: This was a
      randomized, multicenter, double-blind, placebo-controlled study of children with
      asthma aged 6 to 14 years. No minimum asthma symptoms were required, and patients
      could continue inhaled corticosteroid (ICS) use. Montelukast, 5 mg, chewable
      tablet (n = 580) or matching placebo (n = 582) was taken the night before the
      first day of school and nightly thereafter for 8 weeks. The primary end point was
      the percentage of days with worsening asthma, defined by one of the following:
      (1) increased beta-agonist use, (2) increased daytime symptoms, (3) awake "all
      night," (4) oral corticosteroid rescue or increased ICS use for worsening asthma,
      or (5) unanticipated health care utilization. RESULTS: The reduction in the
      percentage of days with worsening asthma with montelukast use versus placebo use
      was not significant (24.3% vs 27.2%, P = .07). Prespecified subgroup analyses
      demonstrated nonsignificant trends favoring montelukast therapy in boys and older
      children but no effect by baseline ICS use or history of cold symptoms. Post hoc
      analysis showed a nonsignificant trend favoring montelukast therapy in reducing
      worsening asthma days for children commencing school after August 15 compared
      with earlier commencement. CONCLUSIONS: Montelukast use was not significantly
      more effective than was placebo use in reducing the percentage of days with
      worsening asthma when initiated at the start of the school year. The effect of
      montelukast treatment on the fall peak in asthma burden may depend on sex, age,
      and the date of school return.

PMID- 20674831
TI  - Clinical efficacy of asian ladybug whole-body extract skin testing.

PMID- 20674832
TI  - A new autosomal recessive, heterozygous pair of mutations of CYBA in a patient
      with chronic granulomatous disease.

PMID- 20674833
TI  - Severe anaphylaxis to hymenoptera stings: does the basal serum tryptase
      concentration really matter?

PMID- 20674835
TI  - Evaluating the effectiveness of medications in the treatment of allergic
      rhinitis.

PMID- 20674834
TI  - Subcutaneous immunoglobulin infusion to treat infants and toddlers with antibody
      deficiencies.

PMID- 20674837
TI  - Modified protocol for desensitization to glatiramer acetate.

PMID- 20674838
TI  - Prophylaxis against Leptospirosis using a nosode: can this large cohort study
      serve as a model for future replications?

PMID- 20674839
TI  - Large-scale application of highly-diluted bacteria for Leptospirosis epidemic
      control.
AB  - BACKGROUND: Leptospirosis is a zoonotic disease of major importance in the
      tropics where the incidence peaks in rainy seasons. Natural disasters represent a
      big challenge to Leptospirosis prevention strategies especially in endemic
      regions. Vaccination is an effective option but of reduced effectiveness in
      emergency situations. Homeoprophylactic interventions might help to control
      epidemics by using highly-diluted pathogens to induce protection in a short time
      scale. We report the results of a very large-scale homeoprophylaxis (HP)
      intervention against Leptospirosis in a dangerous epidemic situation in three
      provinces of Cuba in 2007. METHODS: Forecast models were used to estimate
      possible trends of disease incidence. A homeoprophylactic formulation was
      prepared from dilutions of four circulating strains of Leptospirosis. This
      formulation was administered orally to 2.3 million persons at high risk in an
      epidemic in a region affected by natural disasters. The data from surveillance
      were used to measure the impact of the intervention by comparing with historical
      trends and non-intervention regions. RESULTS: After the homeoprophylactic
      intervention a significant decrease of the disease incidence was observed in the
      intervention regions. No such modifications were observed in non-intervention
      regions. In the intervention region the incidence of Leptospirosis fell below the
      historic median. This observation was independent of rainfall. CONCLUSIONS: The
      homeoprophylactic approach was associated with a large reduction of disease
      incidence and control of the epidemic. The results suggest the use of HP as a
      feasible tool for epidemic control, further research is warranted.

PMID- 20674840
TI  - Chelidonium majus 30C and 200C in induced hepato-toxicity in rats.
AB  - INTRODUCTION: Homeopathy is a popular form of complementary and alternative
      medicine and is used to treat for certain liver ailments. AIM: To analyze the
      efficacy of homeopathic Chelidonium majus (Chel) 30C and 200C in amelioration of
      experimentally induced hepato-toxicity in rats. METHODS: Rats were randomized
      into six sub-groups: negative control; negative control+EtOH; positive control;
      positive control+EtOH group; Chel 30; Chel 200. Rats were sacrificed at day 30,
      60, 90 and 120; various toxicity biomarkers and pathological parameters were
      evaluated. Gelatin zymography for determination of metalloproteinases activity
      and Western blot of p53 and Bcl-2 proteins were also employed. All analyses were
      observer blind. RESULTS: Chronic feeding of p-dimethyl amino azo benzene (p-DAB)
      and phenobarbital (PB) elevated the levels of aspartate aminotransferase (AST),
      alanine aminotransferase (ALT), gamma glutamyl transferase (GGT), lactate
      dehydrogenase (LDH), triglyceride, cholesterol, creatinine and bilirubin and
      lowered the levels of glutathione (GSH), glucose-6-phosphate dehydrogenase (G-6
      PD), catalase and HDL-cholesterol. There were statistically significant
      modulations of these parameters in the treated animals, compared to positive
      controls. In both treated groups, there was downregulation of metalloproteinases,
      p53 and Bcl-2 proteins compared to over-expression in the positive control
      groups. CONCLUSION: Both the potencies of Chel exhibited anti-tumor and anti
      oxidative stress potential against artificially induced hepatic tumors and hepato
      toxicity in rats. More studies are warranted.

PMID- 20674841
TI  - Heparin-binding epidermal growth factor expression in KATO-III cells after
      Helicobacter pylori stimulation under the influence of strychnos Nux vomica and
      Calendula officinalis.
AB  - INTRODUCTION: Previous studies have shown the stimulating effect of Helicobacter
      pylori on the gene expression of heparin-binding epidermal growth factor (HB-EGF)
      using the gastric epithelial cell line KATO-III. Strychnos Nux vomica (Nux
      vomica) and Calendula officinalis are used in highly diluted form in homeopathic
      medicine to treat patients suffering from gastritis and gastric ulcers. AIM AND
      METHOD: To investigate the influence of Nux vomica and Calendula officinalis on
      HB-EGF-like growth factor gene expression in KATO-III cells under the stimulation
      of H. pylori strain N6 using real-time PCR with and without addition of Nux
      vomica and Calendula officinalis as a 10c or 12c potency. RESULTS: Baseline
      expression and stimulation were similar to previous experiments, addition of Nux
      vomica 10c and Calendula officinalis 10c in a 43% ethanolic solution led to a
      significant reduction of H. pylori induced increase in gene expression of HB-EGF
      (reduced to 53.12+/-0.95% and 75.32+/-1.16% vs. control; p<0.05), respectively.
      Nux vomica 12c reduced HB-EGF gene expression even in dilutions beyond Avogadro's
      number (55.77+/-1.09%; p<0.05). Nux vomica 12c in a 21.5% ethanol showed a
      smaller effect (71.80+/-3.91%, p<0.05). This effect was only be observed when the
      drugs were primarily prepared in ethanol, not in aqueous solutions. The data
      suggest that both drugs prepared in ethanolic solution are potent inhibitors of
      H. pylori induced gene expression.

PMID- 20674842
TI  - Preliminary investigation of metal and metalloid contamination of homeopathic
      products marketed in Croatia.
AB  - BACKGROUND: Due to their popularity as a complementary therapy in many diseases,
      homeopathic products of animal, vegetable, mineral and chemical origin should be
      tested for the presence of contaminants to prevent eventual toxic effects.
      OBJECTIVE: Thirty samples of homeopathic products were analyzed to estimate
      possible contamination with potentially toxic elements: Pb, Cd, As, Hg, Cr, Ni
      and Zn, and to assess human exposure to these metals/metalloid as a consequence
      of their consumption. METHODS: Atomic absorption spectrometry was used to
      determine metal and metalloid concentrations. RESULTS: Most tested products had
      very low metal/metalloid levels (below the limit of quantification of the
      method), but the metal/metalloid levels in the remaining products were in the
      following ranges (in microg g(-1)): Pb 0.33-1.29 (6 samples), Cd 2.78 (1 sample),
      As 0.22 (1 sample), Hg 0.02-0.12 (24 samples), Cr 0.40-10.27 (10 samples), Ni
      0.43-55.00 (19 samples), and Zn 2.20-27.80 (11 samples). In the absence of
      regulatory standards for homeopathic products, the obtained results were compared
      to maximum allowable levels (MALs) as proposed by USP Ad Hoc Advisory Panel. Some
      analyzed preparations had metal levels above MALs (Pb: 2 samples; Cd: 1 sample;
      Ni: 2 samples). However, estimated cumulative daily intakes from tested
      homeopathic products were in all cases lower than permitted daily exposures for
      all dosage forms. CONCLUSION: The risk of bioaccumulation of metals/metalloid
      from the homeopathic medicines seems to be rather low, due to small quantities of
      those products prescribed to be applied per day, as well as insignificant metal
      contamination of the majority of tested products. However, the fact that
      particular formulations were contaminated by metals above MALs indicates
      potential risk and points to the necessity of regular monitoring of homeopathic
      products for metal contamination, due to their frequent and mostly unsupervised
      use.

PMID- 20674843
TI  - Database on veterinary clinical research in homeopathy.
AB  - OBJECTIVE: The aim of the present report is to provide an overview of the first
      database on clinical research in veterinary homeopathy. PROCEDURES: Detailed
      searches in the database 'Veterinary Clinical Research-Database in Homeopathy'
      (http://www.carstens-stiftung.de/clinresvet/index.php). RESULTS: The database
      contains about 200 entries of randomised clinical trials, non-randomised clinical
      trials, observational studies, drug provings, case reports and case series.
      Twenty-two clinical fields are covered and eight different groups of species are
      included. The database is free of charge and open to all interested veterinarians
      and researchers. CONCLUSION: The database enables researchers and veterinarians,
      sceptics and supporters to get a quick overview of the status of veterinary
      clinical research in homeopathy and alleviates the preparation of systematical
      reviews or may stimulate reproductions or even new studies.

PMID- 20674844
TI  - Semi-standardised homeopathic treatment of premenstrual syndrome with a limited
      number of medicines: feasibility study.
AB  - BACKGROUND: Individualised homeopathy involves a large number of possible
      medicines. For clinical research purposes it is desirable to limit this number,
      create more consistency between prescribers and optimising the accuracy of
      prescription. Using a semi-standardised treatment protocol, we aimed to improve
      homeopathic management of targeted subgroups of women with premenstrual
      syndrome/symptoms (PMS/S). OBJECTIVES: To design a semi-standardised protocol for
      individualised prescribing in PMS/S with a limited number of homeopathic
      medicines, and to explore the feasibility of working with it in daily homeopathic
      practice. METHODS: With help of an expert panel, homeopathic medicines were
      selected, as well as predictive symptoms and characteristics (keynotes) for each
      medicine. With those, we designed a patient questionnaire and a diagnostic
      algorithm. The patient questionnaire contained 123 questions, representing
      potential predictive symptoms for 11 homeopathic medicines for PMS/S. The
      medicines selected (in rank order) were Sep, Nat-m, Lach, Cimic, Lac-c, Puls,
      Calc, Lil-t, Mag-p, Mag-c, Phos. In a feasibility study 20 homeopathic doctors
      used the protocol in daily practice. The diagnosis was confirmed by daily rating
      of pre-defined symptoms during two consecutive menstrual cycles. The
      acceptability and feasibility of the protocol were evaluated after 3 months
      follow-up, at which time we also measured changes in premenstrual symptom scores
      and patient-reported changes in symptoms and general health. RESULTS: The doctors
      mostly complied with the protocol and valued the computerised diagnostic
      algorithm as a useful tool for homeopathic medicine selection. 33 patients
      completed 3 months follow-up. By then, 19 patients still taking the first
      medicine on the basis of the algorithm. We received valid symptom records of 30
      patients. Premenstrual symptom scores dropped by 50% or more in 12 patients and
      by 30-50% in 6 patients; scores dropped by less than 30% or increased in 12
      patients. Recruitment of patients (n=38 in 9 months) proved difficult. Adherence
      to the diaries and the questionnaire was satisfactory. CONCLUSIONS: It is
      feasible to use a semi-standardised protocol for individualised homeopathic
      prescribing in PMS, in daily practice. Its predictive value and the percentage of
      women with PMS/S helped by the selected medicines remain to be evaluated in
      further research. In future research, active promotion will be needed to recruit
      patients.

PMID- 20674845
TI  - Case history: individualized homeopathy and severe chronic idiopathic neutropenia
      (SCN).
AB  - BACKGROUND: Severe chronic neutropenia (SCN) places the sufferer at increased
      risk of bacterial infection, often requiring emergency hospital admission and
      long-term antibiotic treatment. METHOD: A single clinical case study of
      idiopathic SCN in a boy of 3 years and 8 months at the start of treatment
      individualized, classical homeopathic treatment was given. Neutrophil count was
      measured at: 5, 17, 21, 29 and 41 months after commencing treatment. RESULTS: Low
      neutrophil count (0.6 and 0.3 x 10(9)/L) was documented for 17 months prior to
      commencing treatment. After 17 months of individualized homeopathy, neutrophil
      count was 1.74, rising to 2.22 at 21 and 3.4 at 29 months treatment. Forty-one
      months after commencing treatment neutrophil count was 3.8 with an intermediate
      peak of 9 recorded during the year. As the child found the procedure distressing,
      blood testing was then discontinued by the parents. CONCLUSIONS: The child
      received no other treatment, including complementary medicine or antibiotics,
      while receiving homeopathic treatment. Individualized homeopathic intervention
      may be the catalyst for the resolution of idiopathic SCN in this case. However,
      as this was a single case, a controlled study is recommended as a next step.

PMID- 20674846
TI  - Hong Kong homeopathy: how it arrived and how it connected with Chinese medicine.
AB  - Translated as 'Shunshi Liaofa' in Mandarin, homeopathy received considerable
      attention from local physicians, thanks to Dr Heribert Schmidt who shared his
      views on the similarities between this western medical therapy and Chinese
      medicine during his visit to Hong Kong in 1954. Considered widely as non
      scientific and superstitious, Chinese medicine was pushed to the periphery during
      the 1950s. On the contrary, adopted by western advanced countries, homeopathy was
      generally regarded as scientific and reliable. Schmidt's acknowledgement of the
      scientific roots of Chinese medicine excited many traditional therapists. The
      purpose of this paper is to trace the history of how homeopathy was introduced to
      Hong Kong and discuss its relationship with scientification of Chinese medicine.

PMID- 20674847
TI  - The concept of health - in the history of medicine and in the writings of
      Hahnemann.
AB  - The number of notions of health is not infinite. In the history of medicine we
      can only find a number of different conceptions or paradigmatic ideas of health,
      in a variety of references and combinations. Health was seen as: 1. harmonious
      balance between principles or entities, 2. result of a struggle against opposing
      forces, 3. continuous dialectical process, 4. hierarchy of components or
      functions, 5. potential to perform and to develop, 6. transcendence towards
      higher levels of being, 7. result of conscious autonomous action, 8. optimal
      causal functioning, or 9. public task and responsibility. Hahnemann's view of
      health, as reflected in his writings, utilized virtually all of these elements.
      They reappear for instance as: 1. harmonious tuning of the life force, 2. defeat
      of pathogenetic influences, 3. admittance of aggravations, 4. autocracy of the
      spirit-like life principle, 5. reference to a higher goal of human existence, 6.
      perfecting character of medical service, 7. concern about dietetics and life
      style, 8. utilization of causality and natural science, and 9. appealing to
      governmental provisions and medical police. These paradigms have been repeatedly
      recombined and applied. The theory of medicine is the attempt to analyze, adjust,
      and develop concepts that meet the demand of contemporary medical practice.
      Medical theory lies between the fields of observable facts and metaphysical
      convictions. Distinguishing the levels of practice, theory, and metaphysics could
      allow the open discussion of theoretical issues, such as the concept of health or
      disease, without raising purely theoretical objections to well-established
      practice.

PMID- 20674848
TI  - 20 years ago: The British Homoeopathic Journal, July 1990.

PMID- 20674849
TI  - "Homeopathy: ex nihilo fit nihil"?

PMID- 20674850
TI  - Central sensitization versus synaptic long-term potentiation (LTP): a critical
      comment.

PMID- 20674851
TI  - Synaptic plasticity and central sensitization: author reply.

PMID- 20674852
TI  - Conflicts of interest and conflicting views on physician compensation: fee-for
      service versus salaried medicine.

PMID- 20674853
TI  - Transfer of cholesterol by the NPC team.
AB  - The mechanisms of intracellular cholesterol transport are largely unknown. In
      this issue of Cell Metabolism, Wang et al. (2010) identify amino acid residues on
      the lumenal lysosomal protein Niemann-Pick C2 (NPC2) that are required for
      intralysosomal transfer of endocytosed cholesterol to membrane-bound NPC1 via a
      process that avoids movement of hydrophobic cholesterol through the aqueous
      phase.

PMID- 20674854
TI  - A clock ticks in pancreatic beta cells.
AB  - Circadian rhythm is a pervasive feature of life, programmed by the conserved core
      clock machinery. A recent study in Nature (Marcheva et al., 2010) reveals that
      core clock components regulate beta cell function and integrate insulin secretion
      into rhythmic metabolic regulation, providing new insight into the pathogenesis
      of diabetes.

PMID- 20674855
TI  - A new way to lower blood pressure: pass the chili peppers please!
AB  - Activation of TRPV1 channels in sensory nerves by capsaicin promotes neuropeptide
      release, leading to the perception of pain and inflammation. In this issue, Yang
      et al. (2010) demonstrate that vascular TRPV1 mediates a beneficial effect of
      capsaicin in the cardiovascular system, promoting nitric oxide release and
      lowering blood pressure.

PMID- 20674856
TI  - Our unindicted coconspirators: human metabolism from a microbial perspective.
AB  - The human gut is populated by a microbiota composed of tens of trillions of
      organisms and millions of genes that together form a metabolic "organ." Intra-
      and interpersonal differences in the structure and functions of this organ
      suggest that it could contribute to our normal metabolic variations and also to
      metabolic disorders. This Commentary discusses experimental approaches for
      connecting microbial and host metabolism in the context of health and disease.

PMID- 20674857
TI  - Rim2alpha determines docking and priming states in insulin granule exocytosis.
AB  - Insulin secretion is essential for maintenance of glucose homeostasis, but the
      mechanism of insulin granule exocytosis, the final step of insulin secretion, is
      largely unknown. Here, we investigated the role of Rim2alpha in insulin granule
      exocytosis, including the docking, priming, and fusion steps. We found that
      interaction of Rim2alpha and Rab3A is required for docking, which is considered a
      brake on fusion events, and that docking is necessary for K(+)-induced
      exocytosis, but not for glucose-induced exocytosis. Furthermore, we found that
      dissociation of the Rim2alpha/Munc13-1 complex by glucose stimulation activates
      Syntaxin1 by Munc13-1, indicating that Rim2alpha primes insulin granules for
      fusion. Thus, Rim2alpha determines docking and priming states in insulin granule
      exocytosis depending on its interacting partner, Rab3A or Munc13-1, respectively.
      Because Rim2alpha(-/-) mice exhibit impaired secretion of various hormones stored
      as dense-core granules, including glucose-dependent insulinotropic polypeptide,
      growth hormone, and epinephrine, Rim2alpha plays a critical role in exocytosis of
      these dense-core granules.

PMID- 20674858
TI  - Activation of TRPV1 by dietary capsaicin improves endothelium-dependent
      vasorelaxation and prevents hypertension.
AB  - Some plant-based diets lower the cardiometabolic risks and prevalence of
      hypertension. New evidence implies a role for the transient receptor potential
      vanilloid 1 (TRPV1) cation channel in the pathogenesis of cardiometabolic
      diseases. Little is known about impact of chronic TRPV1 activation on the
      regulation of vascular function and blood pressure. Here we report that chronic
      TRPV1 activation by dietary capsaicin increases the phosphorylation of protein
      kinase A (PKA) and eNOS and thus production of nitric oxide (NO) in endothelial
      cells, which is calcium dependent. TRPV1 activation by capsaicin enhances
      endothelium-dependent relaxation in wild-type mice, an effect absent in TRPV1
      deficient mice. Long-term stimulation of TRPV1 can activate PKA, which
      contributes to increased eNOS phosphorylation, improves vasorelaxation, and
      lowers blood pressure in genetically hypertensive rats. We conclude that TRPV1
      activation by dietary capsaicin improves endothelial function. TRPV1-mediated
      increase in NO production may represent a promising target for therapeutic
      intervention of hypertension.

PMID- 20674859
TI  - Myeloid type I interferon signaling promotes atherosclerosis by stimulating
      macrophage recruitment to lesions.
AB  - Inflammatory cytokines are well-recognized mediators of atherosclerosis.
      Depending on the pathological context, type I interferons (IFNs; IFNalpha and
      IFNbeta) exert either pro- or anti-inflammatory immune functions, but their exact
      role in atherogenesis has not been clarified. Here, we demonstrate that IFNbeta
      enhances macrophage-endothelial cell adhesion and promotes leukocyte attraction
      to atherosclerosis-prone sites in mice in a chemokine-dependent manner. Moreover,
      IFNbeta treatment accelerates lesion formation in two different mouse models of
      atherosclerosis and increases macrophage accumulation in the plaques.
      Concomitantly, absence of endogenous type I IFN signaling in myeloid cells
      inhibits lesion development, protects against lesional accumulation of
      macrophages, and prevents necrotic core formation. Finally, we show that type I
      IFN signaling is upregulated in ruptured human atherosclerotic plaques. Hereby,
      we identify type I IFNs as proatherosclerotic cytokines that may serve as
      additional targets for prevention or treatment.

PMID- 20674860
TI  - Cardiolipin remodeling by ALCAT1 links oxidative stress and mitochondrial
      dysfunction to obesity.
AB  - Oxidative stress causes mitochondrial dysfunction and metabolic complications
      through unknown mechanisms. Cardiolipin (CL) is a key mitochondrial phospholipid
      required for oxidative phosphorylation. Oxidative damage to CL from pathological
      remodeling is implicated in the etiology of mitochondrial dysfunction commonly
      associated with diabetes, obesity, and other metabolic diseases. Here, we show
      that ALCAT1, a lyso-CL acyltransferase upregulated by oxidative stress and diet
      induced obesity (DIO), catalyzes the synthesis of CL species that are highly
      sensitive to oxidative damage, leading to mitochondrial dysfunction, ROS
      production, and insulin resistance. These metabolic disorders were reminiscent of
      those observed in type 2 diabetes and were reversed by rosiglitazone treatment.
      Consequently, ALCAT1 deficiency prevented the onset of DIO and significantly
      improved mitochondrial complex I activity, lipid oxidation, and insulin signaling
      in ALCAT1(-/-) mice. Collectively, these findings identify a key role of ALCAT1
      in regulating CL remodeling, mitochondrial dysfunction, and susceptibility to
      DIO.

PMID- 20674861
TI  - Identification of surface residues on Niemann-Pick C2 essential for hydrophobic
      handoff of cholesterol to NPC1 in lysosomes.
AB  - Water-soluble Niemann-Pick C2 (NPC2) and membrane-bound NPC1 are cholesterol
      binding lysosomal proteins required for export of lipoprotein-derived cholesterol
      from lysosomes. The binding site in NPC1 is located in its N-terminal domain
      (NTD), which projects into the lysosomal lumen. Here we perform alanine-scanning
      mutagenesis to identify residues in NPC2 that are essential for transfer of
      cholesterol to NPC1(NTD). Transfer requires three residues that form a patch on
      the surface of NPC2. We previously identified a patch of residues on the surface
      of NPC1(NTD) that are required for transfer. We present a model in which these
      two surface patches on NPC2 and NPC1(NTD) interact, thereby opening an entry pore
      on NPC1(NTD) and allowing cholesterol to transfer without passing through the
      water phase. We refer to this transfer as a hydrophobic handoff and hypothesize
      that this handoff is essential for cholesterol export from lysosomes.

PMID- 20674863
TI  - Intestinal specific LXR activation stimulates reverse cholesterol transport and
      protects from atherosclerosis.
AB  - Several steps of the HDL-mediated reverse cholesterol transport (RCT) are
      transcriptionally regulated by the nuclear receptors LXRs in the macrophages,
      liver, and intestine. Systemic LXR activation via synthetic ligands induces RCT
      but also causes increased hepatic fatty acid synthesis and steatosis, limiting
      the potential therapeutic use of LXR agonists. During the last few years, the
      participation of the intestine in the control of RCT has appeared more evident.
      Here we show that while hepatic-specific LXR activation does not contribute to
      RCT, intestinal-specific LXR activation leads to decreased intestinal cholesterol
      absorption, improved lipoprotein profile, and increased RCT in vivo in the
      absence of hepatic steatosis. These events protect against atherosclerosis in the
      background of the LDLR-deficient mice. Our study fully characterizes the
      molecular and metabolic scenario that elects the intestine as a key player in the
      LXR-driven protective environment against cardiovascular disease.

PMID- 20674862
TI  - Diurnal regulation of MTP and plasma triglyceride by CLOCK is mediated by SHP.
AB  - We examined the role of clock genes in the diurnal regulation of plasma
      triglyceride-rich apolipoprotein B-lipoproteins and their biosynthetic chaperone,
      microsomal triglyceride transfer protein (MTP). Clock(mt/mt) mice showed
      sustained hypertriglyceridemia and high MTP expression. CLOCK knockdown activated
      MTP promoter and reduced small heterodimer partner (SHP, NROB2). CLOCK
      upregulated SHP by binding to its E box. SHP suppressed MTP expression by binding
      to the HNF4alpha/LRH-1 at the MTP promoter. Cyclic expression of MTP after serum
      shock was abrogated by siCLOCK and siSHP. Plasma triglyceride and MTP showed
      reduced diurnal variations in Shp(-/-) mice. Whereas peaks and nadirs in SHP
      expression were inversely correlated with those of MTP, these changes were
      reduced in Clock(mt/mt) mice. Expression of Shp abrogated hypertriglyceridemia in
      Clock(mt/mt) mice. Together, these studies describe a role of Clock/Shp in the
      diurnal regulation of MTP and plasma triglyceride and indicate that disruptions
      in circadian regulation might cause hyperlipidemia.

PMID- 20674864
TI  - Iron regulatory proteins secure mitochondrial iron sufficiency and function.
AB  - Mitochondria supply cells with ATP, heme, and iron sulfur clusters (ISC), and
      mitochondrial energy metabolism involves both heme- and ISC-dependent enzymes.
      Here, we show that mitochondrial iron supply and function require iron regulatory
      proteins (IRP), cytosolic RNA-binding proteins that control mRNA translation and
      stability. Mice lacking both IRP1 and IRP2 in their hepatocytes suffer from
      mitochondrial iron deficiency and dysfunction associated with alterations of the
      ISC and heme biosynthetic pathways, leading to liver failure and death. These
      results uncover a major role of the IRPs in cell biology: to ensure adequate iron
      supply to the mitochondrion for proper function of this critical organelle.

PMID- 20674866
TI  - Colonic opacification in a patient with end-stage kidney disease.

PMID- 20674867
TI  - Vomiting and painful abdomen in dementia.

PMID- 20674868
TI  - Probiotics for ulcerative colitis ... Are the good bugs back?

PMID- 20674869
TI  - A necrotic liver mass.

PMID- 20674870
TI  - A rare cause of upper gastrointestinal bleeding.

PMID- 20674871
TI  - Lower gastrointestinal bleeding in a patient with a history of breast cancer.

PMID- 20674872
TI  - Summary of invasive pneumococcal disease burden among children in the Asia
      Pacific region.
AB  - Invasive pneumococcal disease (IPD) burden is significant in the Asia-Pacific
      region. This review describes the epidemiology and Streptococcus pneumoniae (SP)
      serotype distribution of IPD in children in the Asia-Pacific region from studies
      published from 1999 to 2010. IPD incidence varies widely in Asia-Pacific
      countries depending on the method of surveillance, the population studied, and
      the time period. Incidences are highest for younger children, with rates near 100
      200 cases per 100,000 children aged <1 or 2 years. Incidences of preventable
      disease are estimated to be 6-200 cases per 100,000. Heptavalent pneumococcal
      conjugate vaccine (PCV7) serotype coverage shows a very wide range over the Asia
      Pacific region. Ten countries have high vaccine serotype coverage (>70%), and six
      countries have low vaccine serotype coverage (<50%). The majority of SP serotypes
      in children with IPD in most countries in the Asia-Pacific region are susceptible
      to penicillin (intermediate and resistant <50%); a few countries have SP
      serotypes with high level resistance to penicillin (intermediate and resistant
      >50%). Japan, Taiwan, and Thailand have high PCV7 serotype coverage. Countries
      with low pneumococcal resistance to antimicrobials have shown increasingly higher
      nonsusceptibility with time. National vaccination programmes that include PCV7,
      10-valent pneumococcal conjugate vaccine (PCV), or 13-valent PCV would
      significantly affect IPD burden in children aged <5 years in the Asia-Pacific
      region, as well as the burden of penicillin-nonsusceptible IPD.

PMID- 20674873
TI  - Dual expression system for assembling phage lambda display particle (LDP) vaccine
      to porcine Circovirus 2 (PCV2).
AB  - The bacteriophage lambda small capsid protein D forms trimers on the phage head.
      D-fusion polypeptides can be expressed from plasmids in E. coli and remain
      soluble without aggregation. We report a dual expression system for the display
      of four immunodominant regions of porcine Circovirus 2 (PCV2) capsid protein
      (CAP) as D-CAP fusions on lambda display particles (LDP). The LDP-D-CAP
      preparation proved an effective vaccine in pigs, eliciting both cellular and
      humoral immune responses and PCV2 neutralizing antibodies. In our dual system
      wild type D expression was encoded by a heteroimmune infecting phage. The D
      fusion protein expression in the infected cells was from an inducible plasmid,
      enabling the deferral of D-fusion expression until needed. The effective vaccine
      preparation depended upon the gradient purification of very high concentration,
      essentially tail-less display particles, not previously described.

PMID- 20674874
TI  - Vaccination with peptide mimotopes produces antibodies recognizing bacterial
      capsular polysaccharides.
AB  - A phage display peptide library was screened using a panel of antibodies to the
      capsular polysaccharides of Streptococcus agalactiae and Neisseria meningitidis.
      Mimotopes NPDHPRVPTFMA (2-8), LIPFHKHPHHRG (3-2) and EQEIFTNITDRV (G3) showing
      the highest binding capacity and strongest ELISA reaction were selected for
      immunization experiments. These mimotopes were either synthesised as
      oligodeoxynucleotides for DNA immunization or MAP (multiple antigen peptide) for
      peptide immunization. Mimotope-DNA vaccination, particularly for G3, induced
      antibodies recognizing a number of target bacteria. This response was seen after
      the second boost injection and was significantly enhanced by the 3rd boost
      injection with a Th1-associated profile, which was dominated by IgG2a, followed
      by IgG1. Mimotope-MAP immunization also produced strong humoral immune responses
      to the bacteria. Antibodies from G3 DNA immunization reacted with the surface
      molecules of S. agalactiae, N. meningitidis and Escherichia coli K5 shown by
      indirect immunofluorescence staining, indicating a possible localization to the
      bacterial capsule. Antibodies produced both from DNA/MAP immunization reacted
      with purified bacterial capsular polysaccharides by ELISA and were of high
      avidity. We have further characterized peptide G3 by a 'tiling path' study to
      examine the effect of changing individual residues in the peptide in raising
      antibodies, which showed that the EIFTN motif in G3 was important in generating
      antibodies to several capsulated bacteria. We conclude that mimotope immunization
      with DNA or MAP potentially induces strong antibody responses against
      encapsulated bacteria. It is suggested that the antibody targets are
      polysaccharides, and these antibodies may cross react at least among closely
      related species of bacteria.

PMID- 20674875
TI  - First report of Streptococcus pneumoniae serotype 6D isolates from invasive
      infections.
AB  - We report the first invasive Streptococcus pneumoniae isolates of serotype 6D and
      the first occurrence of this serotype in Europe. Till now, the appearance of
      serotype 6D pneumococci in nasopharyngeal carriage has been speculated to be
      associated with a selective pressure from vaccination with the conjugated 7
      valent antipneumococcal vaccine. Our observations indicate that this serotype is
      present also among unvaccinated individuals in the population where mass infant
      vaccination has not yet been introduced. Importantly, these strains were isolated
      from invasive infections, indicating the full virulence potential of pneumococci
      belonging to serotype 6D and its importance for future vaccine formulations.

PMID- 20674876
TI  - Severe combined immunodeficiency (SCID) and rotavirus vaccination: reports to the
      Vaccine Adverse Events Reporting System (VAERS).
AB  - BACKGROUND: Rotavirus vaccines are the only live vaccines recommended for infants
      in the US. Postmarketing reports have described severe gastroenteritis with
      vaccine viral shedding in infants who received rotavirus vaccine and were later
      diagnosed with SCID. The US Food and Drug Administration recently approved
      labeling changes for RotaTeq and Rotarix contraindicating administration to
      individuals with a history of SCID. We queried VAERS to characterize reports of
      SCID after rotavirus vaccination. METHODS: VAERS inclusion criteria included
      current US-licensed rotavirus vaccines, report dates from February 3, 2006 to
      January 15, 2010, and queries for the MedDRA preferred term "combined
      immunodeficiency" as well as any text containing the terms, "SCID" or "combined
      immunodeficiency." RESULTS: We identified nine reports of SCID and rotavirus
      vaccination in infants between 3 and 9 months of age. All but one case presented
      with diarrhea among other symptoms. All infants were hospitalized and had workups
      leading to the SCID diagnosis. Stool rotavirus testing was positive in all cases
      and the virus was identified as the vaccine strain in six cases. Prolonged viral
      shedding was documented in five cases. No deaths were reported. CONCLUSION: The
      aforementioned labeling changes were warranted given the risk posed by live
      rotavirus vaccine to individuals with SCID, as illustrated by these VAERS cases.
      Although congenital, SCID was not diagnosed in these infants until after
      rotavirus vaccination. Earlier identification of SCID (e.g., from expanded
      newborn screening or heightened clinical vigilance) could prevent inadvertent
      live rotavirus vaccine administration and also potentially result in earlier life
      saving stem cell transplants.

PMID- 20674877
TI  - HbS and HbC associate with malaria transmission: human genetics links to
      vaccinology?

PMID- 20674878
TI  - Yellow fever vaccination coverage among children in Brazilian capitals.
AB  - Brazil recommends universal yellow fever (YF) vaccination for children who reside
      in or travel to endemic areas. We conducted a household survey to calculate YF
      vaccine coverage among children 18-30 months of age in 27 capital cities. A total
      of 9285 children were surveyed in the 15 cities with YF fever universal
      vaccination; 7290 (79%) had documented evidence of YF vaccination by 12 months of
      age, 7996 (86%) by 18 months of age, and 8479 (91%) prior to the survey. In 12
      cities with selective YF vaccination coverage was only 1% by 18 months of age. YF
      fever vaccination can be improved to reach all children where vaccine is
      recommended.

PMID- 20674879
TI  - Positive effect of the introduction of Haemophilus influenzae type b vaccination
      in the expanded program on immunization in Cameroon.
AB  - The microbiological surveillance of acute bacterial meningitis in the three
      northern provinces of Cameroon, namely North, Far North and Adamaoua shows the
      disappearance of Hib from cerebrospinal fluid specimens examined in the
      laboratory of the Centre Pasteur, in Garoua, using culture and/or soluble antigen
      testing, since the Hib immunization introduction on 1 February 2009.

PMID- 20674880
TI  - Impact of unfounded vaccine safety concerns on the nationwide measles-rubella
      immunization campaign, Georgia, 2008.
AB  - Vaccine safety fears following media reports of adverse events led to low (50.3%)
      coverage in a supplementary measles-rubella immunization campaign in Georgia in
      2008. Review of adverse events associated with the campaign identified 432
      reports (<0.1% of ~ 493,000 vaccinees) including 338 (78.2%) cases of syncope.
      There were no deaths. Causality assessment was performed for 79 cases perceived
      by providers as severe and with clinical details available. Conditions likely
      caused by the vaccine were identified in 13 (16.5%) cases (allergic and local
      reactions, thrombocytopenia). Thirty-seven (46.8%) cases had symptoms consistent
      with syncope or anxiety attack; 36 (97.3%) of them were initially misdiagnosed as
      anaphylactic shock/allergies/"postvaccinal reactions". Twenty-nine (36.7%) cases
      had coincidental illnesses. Safety fears were unfounded and exaggerated by media
      reports and providers' difficulties in recognizing syncope/anxiety attacks. Risk
      communication strategies to address perceived vaccine safety concerns are
      urgently needed to ensure that the goal of measles and rubella elimination in the
      European Region of the World Health Organization is met.

PMID- 20674881
TI  - Report of the 2nd "French Clinical Vaccinology Meeting Jean-Gerard Guillet":
      immunization and respiratory diseases.
AB  - The 2nd French Clinical Vaccinology conference held on 20th April 2009 in Paris
      (France) was a unique opportunity to discuss basic and translational research in
      vaccinology and its implications for patients for respiratory diseases. This
      conference is organized by the Clinical Research Center Cochin-Pasteur, that has
      been involved for several years clinical research in vaccines. We report on here
      the key findings of the conference, especially the immunization of the chronic
      respiratory diseases, the clinical effectiveness of vaccines and the development
      of new vaccines in pulmonology.

PMID- 20674882
TI  - Prevalence of high-risk indications for influenza vaccine varies by age, race,
      and income.
AB  - Estimates of the proportions of the population who are at high risk of influenza
      complications because of prior health status or who are likely to have decreased
      vaccination response because of immunocompromising conditions would enhance
      public health planning and model-based projections. We estimate these proportions
      and how they vary by population subgroups using national data systems for 2006
      2008. The proportion of individuals at increased risk of influenza complications
      because of health conditions varied 10-fold by age (4.2% of children <2 years to
      47% of individuals >64 years). Age-specific prevalence differed substantially by
      gender, by racial/ethnic groups (with African Americans highest in all age
      groups) and by income. Individuals living in families with less than 200% of
      federal poverty level (FPL) were significantly more likely to have at least one
      of these health conditions, compared to individuals with 400% FPL or more (3-fold
      greater among <2 and 30% greater among >64 years). Among children, there were
      significantly elevated proportions in all regions compared to the West. The
      estimated prevalence of immunocompromising conditions ranged from 0.02% in young
      children to 6.14% older adults. However, national data on race/ethnicity and
      income are not available for most immunocompromising conditions, nor is it
      possible to fully identify the degree of overlap between persons with high-risk
      health conditions and with immunocompromising conditions. Modifications to
      current national data collection systems would enhance the value of these data
      for public health programs and influenza modeling.

PMID- 20674883
TI  - Echinacea and its alkylamides: effects on the influenza A-induced secretion of
      cytokines, chemokines, and PGE2 from RAW 264.7 macrophage-like cells.
AB  - The goal of this study was to determine whether extracts and isolated alkylamides
      from Echinacea purpurea would be useful for prevention of the inflammatory
      response that accompanies infections with H1N1 influenza A. Seventeen extracts
      and 4 alkylamides were tested for the ability to inhibit production of cytokines,
      chemokines, and PGE2 from RAW 264.7 macrophage-like cells infected with the H1N1
      influenza A strain PR/8/34. The alkylamides undeca-2Z,4E-diene-8,10-diynic acid
      isobutylamide, dodeca-2E,4E,8Z,10E/Z-tetraenoic acid isobutylamide, dodeca-2E,4E
      dienoic acid isobutylamide, and undeca-2E-ene-8,10-diynoic acid isobutylamide
      suppressed production of TNF-alpha and PGE2 from infected cells. Dodeca-2E,4E
      dienoic acid isobutylamide was especially effective at inhibiting production of
      these mediators and also strongly inhibited production of G-CSF, CCL2/MCP-1,
      CCL3/MIP-1alpha and CCL5/RANTES. In contrast, the ethanol extracts (75%), which
      were prepared from dormant roots of E. purpurea grown in different locations
      throughout North Carolina, displayed a range of effects from suppression to
      stimulation of mediator production. Precipitation of the extracts with ethanol
      removed the stimulatory activity, however, even after precipitation; many of the
      extracts did not display any suppressive activity. Analysis of the extracts
      revealed slight variations in concentration of alkylamides, caftaric acid, and
      cichoric acid, but the activity of the extracts did not strongly correlate with
      concentrations of these compounds. Our in vitro experiments suggest that E.
      purpurea extracts have the potential for use in alleviating the symptoms and
      pathology associated with infections with influenza A; however, further study
      will be necessary to define procedures necessary to unmask the alkylamide
      activity in crude extracts.

PMID- 20674884
TI  - Time flies with music whatever its emotional valence.
AB  - The present study used a temporal bisection task to investigate whether music
      affects time estimation differently from a matched auditory neutral stimulus, and
      whether the emotional valence of the musical stimuli (i.e., sad vs. happy music)
      modulates this effect. The results showed that, compared to sine wave control
      music, music presented in a major (happy) or a minor (sad) key shifted the
      bisection function toward the right, thus increasing the bisection point value
      (point of subjective equality). This indicates that the duration of a melody is
      judged shorter than that of a non-melodic control stimulus, thus confirming that
      "time flies" when we listen to music. Nevertheless, sensitivity to time was
      similar for all the auditory stimuli. Furthermore, the temporal bisection
      functions did not differ as a function of musical mode.

PMID- 20674885
TI  - [Care of ST elevated myocardial infarction patients in Vendee in 2008:
      observational and descriptive study].
AB  - PURPOSE OF THE STUDY: Estimating the quality of care of the patients presenting
      an ST-elevation myocardial infarction in Vendee. PATIENTS AND METHOD: Prospective
      observational study carried out over the year 2008. Included patients presenting
      a myocardial infarction for less than 24 hours, they were alive when emergency
      team arrived, and were taken care of by the SMUR, the emergencies or the
      cardiology of the hospital of La Roche-sur-Yon. RESULTS: Two hundred and
      seventeen patients were included, 163 men and 54 women, average age: 65 years.
      Fifty-six percent of the patients called initially the emergency medical service,
      half of those within an hour after pain began. Seventy-two percent of them were
      looked after by a SMUR. Twenty-six percent consulted initially a general
      practitioner, and one third of those were redirected towards the emergency
      medical service. Thirty percent of all patients followed the ideal procedure
      defined by succession of chest pain, emergency medical service call, SMUR,
      angioplasty or fibrinolysis. The average time between the ECG and the
      fibrinolysis is 36 minutes, or of the arrival in coronarography room is 105
      minutes. The balloon is inflated 42 minutes later. Eighty-six percent of the
      patients taken care of in the acute phase benefited from a strategy of
      reperfusion, primary angioplasty (63%) or fibrinolysis (21%). Ninety percent of
      revascularisations were successful. CONCLUSION: In the case of the chest pain,
      the emergency medical service is under-used. The number of revascularised
      patients is satisfactory, but the whole procedure takes too much time, especially
      when the treatment is the angioplasty.

PMID- 20674886
TI  - Performance on a simple response time task: Is sleep or work more important for
      miners?
AB  - The purpose of the current study was to investigate the impact of work- and sleep
      related factors on an objective measure of response time in a field setting.
      Thirty-five mining operators working 12-h shift patterns completed daily sleep
      and work diaries, wore activity monitors continuously and completed palm-based
      psychomotor vigilance tests (palmPVT) at the start and end of each shift. Linear
      mixed models were used to test the main effects on response time of roster,
      timing of test, sleep history and prior wake. The time at which the test occurred
      was a significant predictor of response time (F3(,)403(.)4 = 6.72, p < .01) with
      the end of night shifts being associated with significantly slower response times
      than the start of night shifts, and the start or end of day shifts. Further, the
      amount of sleep obtained in the 24h prior to the test was also a significant
      predictor of response time (F3(,)407(.)0 = 3.05, p < .01). The results suggest
      that, as expected, the end of night shift is associated with changes in response
      time indicative of performance impairments. Of more interest however is that
      immediate sleep history was also predictive of changes in response time with
      lower amounts of prior sleep related to slower response times. The current data
      provides further evidence that sleep is a primary mediator of performance,
      independent of roster pattern.

PMID- 20674887
TI  - Promoter hypermethylation and expression profile of MGMT and CDH1 genes in oral
      cavity cancer.
AB  - BACKGROUND: Several genetic alterations have been reported to contribute to the
      development of oral squamous cell carcinoma (OSCC). Methylation of CpG-islands in
      cancer-related genes may serve as epigenetic biomarkers for oral cancer diagnosis
      and prognosis. The objective of this study was to analyze methylation profile of
      MGMT and CDH1 genes and their link with expression activity in patients with oral
      cavity cancer. METHODS: Promoter hypermethylation status of MGMT and CDH1 genes
      were assayed by Methylation-specific PCR (MSP) in OSCC (n=76) tissues kept in
      paraffin and normal oral tissues (n=57) served as control. Also, we investigated
      MGMT and CDH1 mRNA levels by real-time quantities reverse transcripts PCR.
      Methylation and mRNA expression profiles of these genes and their association
      with clinical data were determined. RESULTS: Aberrant promoter hypermethylation
      of CDH1 and MGMT genes were detected in 61.8% (47 of 76) and 73.7% (56 of 76) of
      the OSCC cases, respectively, with significant difference between cases and
      controls for MGMT (P=0.027). CDH1 promoter methylation in cases and healthy
      controls was not significant. The mRNA expression level results showed
      statistically significant (P=0.03) differences between cases and healty controls
      for the MGMT gene. However, the difference for the CDH1 gene was not significant.
      CONCLUSION: Our findings, for the first time, in a South-Eastern Iranian
      population, indicate that the two genes are aberrantly methylated in OSCC, and
      that MGMT methylation may be considered as a potential molecular marker for the
      poor survival in advanced OSCC.

PMID- 20674888
TI  - Movement decoupling: A self-help intervention for the treatment of
      trichotillomania.
AB  - Trichotillomania (TTM) is classified as an impulse control disorder characterized
      by the recurrent urge to pull out one's own hair resulting in noticeable hair
      loss. Cognitive-behavioral therapy, involving habit reversal training, currently
      represents the treatment of choice. The present study assessed the feasibility
      and effectiveness of a novel self-help technique, entitled decoupling (DC). DC
      aims at attenuating TTM by performing movements that decouple the behavioral
      elements involved in hair pulling. A total of 42 subjects with TTM were recruited
      via self-help forums for TTM and were randomized either to DC or progressive
      muscle relaxation (PMR). After four weeks, participants were asked to fill out
      the same questionnaires as before and rate the effectiveness of the intervention.
      The completion rate was high and the reliability of the assessments at least
      satisfactory. The DC group showed a significantly greater decline on the
      Massachusetts General Hospital - Hair-Pulling Scale, which served as the primary
      outcome, relative to PMR indicating a medium to strong effect size. Declines on
      scales tapping depression and obsessive-compulsive disorder were comparable
      between the two groups. Despite some methodological limitations and the need for
      replication including follow-up and expert ratings, the present study suggests
      that DC may prove beneficial to a substantial number of individuals affected with
      TTM.

PMID- 20674889
TI  - [Resident training in breast surgery].

PMID- 20674890
TI  - God: Do I have your attention?
AB  - Religion is commonly defined as a set of rules, developed as part of a culture.
      Here we provide evidence that practice in following these rules systematically
      changes the way people attend to visual stimuli, as indicated by the individual
      sizes of the global precedence effect (better performance to global than to local
      features). We show that this effect is significantly reduced in Calvinism, a
      religion emphasizing individual responsibility, and increased in Catholicism and
      Judaism, religions emphasizing social solidarity. We also show that this effect
      is long-lasting (still affecting baptized atheists) and that its size
      systematically varies as a function of the amount and strictness of religious
      practices. These findings suggest that religious practice induces particular
      cognitive-control styles that induce chronic, directional biases in the control
      of visual attention.

PMID- 20674891
TI  - Density, connectedness and attentional capture in hierarchical patterns: evidence
      from simultanagnosia.
AB  - We examined the effects of different grouping cues (item density, number and
      connectedness) on the ability of a patient with simultanagnosia (GK) to identify
      compound stimuli. In Experiment 1, the effects of density and connectedness on
      the recognition of global and local forms were examined. In Experiment 2, the
      spatial distance of local elements was manipulated by varying the size of the
      global forms and the number of local elements, to assess whether the distance
      between the local elements or their number determined the effects on global/local
      processing in disconnected patterns. The results showed that high item density
      and connectedness, each facilitates the grouping of local elements into global
      shapes, determined the explicit recognition of global stimuli in simultanagnosia.
      Moreover, in addition to any bias to attend to the local level, there was also
      evidence for attentional capture by stimuli at the global level. The data
      indicate that grouping processes still operate in simultanagnosia and can
      overcome biases to select at a local level. Any biases in selection can also be
      compounded by poor attentional disengagement.

PMID- 20674892
TI  - [Grade of knowledge about the advance directive document by the chronic patient
      who comes to the emergency department].
AB  - OBJECTIVE: To evaluate the patient's and their caregiver's knowledge of the
      advance directive document (ADD) in patients with chronic diseases who come to
      the emergency department due to decompensation and their caregivers. To discover
      the patient's willingness and associated factors to draw up an ADD. MATERIAL AND
      METHODS: A descriptive cohort study including patients with an acutely
      decompensated chronic evolving disease attending the ED medicine section at an
      urban tertiary teaching hospital was performed. The patients' demographic and
      clinical variables were recorded. After control of their symptoms, an anonymous
      structured oral interview was also administered. Dependent variables included
      were previous knowledge of the ADD, and the patient willingness to draw it up.
      The relationship among independent and dependent variables was analyzed. RESULTS:
      A total of 380 people (190 patients and 190 carers) were analyzed. Compared with
      patients, carers were more frequently women (76% vs 42%, p<0.001), younger (58+/
      15 vs 73+/-12, p<0.001), and had a better knowledge of the disease (88% vs 74%,
      p<0.001) and of the ADD (28% vs 16%, p<0.001). Only 5% of the patients had
      received ADD information from their physician. The only factor associated with
      the patients' previous knowledge of the ADD was to have completed at least
      secondary school (p<0.05). Forty-six percent of patients were favorable to the
      drawing up of an ADD. The only variable associated with such a willingness was to
      be 70 or younger (p<0.05). Eighty-eight percent of the patients were in favor of
      the distribution of information leaflets in the ED. CONCLUSIONS: There is poor
      patient and carer knowledge regarding the ADD among patients with chronic
      diseases. Nonetheless, almost half of patients would be willing to draw up an
      ADD. EDs can contribute to improve the information about it.

PMID- 20674893
TI  - Age-related changes in the localization of DNA methyltransferases during meiotic
      maturation in mouse oocytes.
AB  - The effects of maternal aging on the localization of DNA methyltransferases were
      evaluated during mouse oocyte maturation using fluorescence staining. And we
      conclude that maternal aging affects the cytoplasmic-to-nuclear trafficking of
      DNA methyltransferases in mouse oocytes during the time from germinal vesicle
      breakdown to metaphase I.

PMID- 20674894
TI  - Angiotensin-(1-7), its receptor Mas, and the angiotensin-converting enzyme type 2
      are expressed in the human ovary.
AB  - OBJECTIVE: To investigate whether angiotensin (Ang)-(1-7), its receptor Mas, and
      angiotensin-converting enzyme type 2 (ACE2) are present in human ovary. DESIGN:
      Cross-sectional study. SETTING: Academic hospital. PATIENT(S): Twelve
      reproductive-age women and five postmenopausal women undergoing oophorectomy for
      nonovarian diseases and seven women having controlled ovarian hyperstimulation
      for IVF. INTERVENTION(S): Ovarian tissue was obtained from the reproductive-age
      women and postmenopausal women undergoing oophorectomy for nonovarian diseases.
      Follicular fluid (FF) samples were obtained from the women having controlled
      ovarian hyperstimulation for IVF. MAIN OUTCOME MEASURE(S): Localization of Ang-(1
      7) and Mas by immunohistochemistry; measurement of Ang-(1-7) in ovarian FF by
      RIA; detection of messenger RNAs encoding Mas and ACE2 with use of real-time
      polymerase chain reaction; assessment of 125I-labeled Ang-(1-7) binding to
      ovarian sections with use of autoradiographic binding assay. RESULT(S):
      Angiotensin-(1-7) and the receptor Mas were localized to primordial, primary,
      secondary, and antral follicles, stroma, and corpora lutea of reproductive-age
      ovaries. Postmenopausal women expressed both the peptide and its receptor in the
      ovarian stroma. Angiotensin-(1-7) was detectable in FF (mean+/-SE: 191+/-54
      pg/mL). Both Mas and ACE2 messenger RNAs were expressed in ovarian tissue, as
      revealed by real-time polymerase chain reaction, and ovarian binding sites for
      125I-labeled Ang-(1-7) were identified by autoradiography. CONCLUSION(S):
      Angiotensin-(1-7), its receptor Mas, and ACE2 are expressed in the human ovary.
      The peptide is present in several ovarian compartments and can be quantified in
      FF.

PMID- 20674895
TI  - A prospective clinical study of interventional ultrasound sclerotherapy on women
      with hydrosalpinx before in vitro fertilization and embryo transfer.
AB  - In this prospective clinical study, ultrasound-guided transvaginal aspiration and
      sclerotherapy with 98% ethanol was performed before the IVF cycle in 33 patients
      with hydrosalpinx. The results showed that ultrasound aspiration and
      sclerotherapy could improve the endometrial receptivity and outcomes of IVF, with
      no recurring sign of the hydrosalpinx and no adverse effect on ovarian reserve or
      responsiveness during the IVF procedure.

PMID- 20674896
TI  - Orthodox Judaism does not necessarily prohibit all multifetal reductions.

PMID- 20674897
TI  - Loss of sympathetic nerve fibers in intestinal endometriosis.
AB  - This study analyzed by immunofluorescence staining the sympathetic innervation in
      the bowel adjacent to the endometriotic lesion and in the healthy tissue at the
      border of the resected specimen. Sympathetic nerve fibers are significantly
      reduced in the mucosal and muscular layer near the endometriotic lesions; in
      contrast, sensory nerve fiber density is not altered in the area near the
      endometriotic lesions.

PMID- 20674899
TI  - What do consistently high-performing in vitro fertilization programs in the U.S.
      do?
AB  - OBJECTIVE: To identify common clinical and laboratory practices among
      consistently high-performing IVF programs. DESIGN: Questionnaire study of
      selected IVF programs. SETTING: Academic and private practice IVF programs.
      PATIENT(S): Ten of 12 programs identified as having consistently high singleton
      delivery rates per cycle. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Common
      clinical practices. RESULT(S): Common clinical practices identified among these
      programs included testing all patients for ovarian reserve, endometrial defects,
      and hydrosalpinges; use of a mixed LH and FSH stimulation protocol with step-down
      dosing; and use of ultrasound guidance for ET. Common laboratory practices
      included selective use of intracytoplasmic sperm injection, group culture of
      embryos in microdrops, and use of blastocyst ET in selected cases. Common
      laboratory features included good air quality using filtration and heated stages
      for oocyte and embryo work. CONCLUSION(S): Although a number of factors were
      identified in this best-practices questionnaire, programs often differed in many
      aspects of care. However, high-performing programs cited experience of
      physicians, embryologists, and staff members as well as consistency of approach,
      attention to detail, and good communication as being vital to excellent outcomes.

PMID- 20674898
TI  - Uterine luminal epithelium-specific proline-rich acidic protein 1 (PRAP1) as a
      marker for successful embryo implantation.
AB  - Proline-rich acidic protein 1 mRNA is highly expressed in the uterine luminal
      epithelium (LE) of day 0.5 mouse uterus, disappears in the preimplantation day
      3.5 uterus, and reappears abundantly in the LE after embryo implantation has
      occurred or upon artificial decidualization. In ovariectomized uterus, Prap1 is
      down-regulated by P, transiently down-regulated by E(2) treatment for 6 hours,
      but dramatically induced by E(2) treatment for 3 days.

PMID- 20674900
TI  - A superior mesenteric vein thrombosis associated with in vitro fertilization.
AB  - OBJECTIVE: To describe a case of superior mesenteric vein thrombosis associated
      with IVF. DESIGN: Case report. SETTING: University teaching hospital. PATIENT(S):
      A 33-year-old female developed progressive abdominal pain several days after ET
      in her first IVF cycle. A computed tomography scan 12 days after ET showed a
      superior mesenteric vein thrombosis. INTERVENTION(S): Therapeutic
      anticoagulation. MAIN OUTCOME MEASURE(S): Resolution of the superior mesenteric
      vein thrombosis with therapeutic anticoagulation. RESULT(S): Early diagnosis and
      treatment of a superior mesenteric vein thrombosis associated with IVF led to a
      favorable outcome. CONCLUSION(S): Endocrine alterations consequent to controlled
      ovarian hyperstimulation for IVF place patients at risk for thromboembolic
      events. Thromboembolic events may occur during an IVF cycle in the absence of
      overt ovarian hyperstimulation, an inherited thrombophilia, or pregnancy. Early
      diagnosis and treatment of superior mesenteric vein thrombosis can lead to a
      favorable outcome. Treatment guidelines for superior mesenteric vein thrombosis
      in setting of IVF are discussed.

PMID- 20674901
TI  - A randomized controlled trial comparing the effectiveness of single versus double
      intrauterine insemination in unexplained infertility.
AB  - In a prospective randomized trial comparing efficacy of double over single
      intrauterine insemination (IUI), 160 couples with unexplained infertility
      underwent controlled ovarian hyperstimulation and IUI. The pregnancy rates were
      similar and statistically not different between groups, suggesting that double
      IUI added no advantage over single IUI.

PMID- 20674902
TI  - Use of high-magnification microscopy for the assessment of sperm recovered after
      two different sperm processing methods.
AB  - OBJECTIVE: To compare the quality of sperm samples obtained after density
      gradient centrifugation and swim-up by performing a nuclear structural analysis
      with high magnification microscopy at *8,000. DESIGN: Prospective and randomized
      split-sample study. SETTING: Reproductive Medicine Center. PATIENT(S): Sperm
      samples from 53 male-partners of couples undergoing infertility treatment.
      INTERVENTION(S): Samples were analyzed by high magnification microscopy before
      and after preparation and classified according the level of nuclear
      vacuolization. MAIN OUTCOME MEASURE(S): Recovery rate, motility rate and
      percentage of sperm scoring each of 4 grades of vacuolization in fresh and
      processed sample. RESULT(S): Both sperm processing methods, swim-up and density
      gradient centrifugation, allow the selection of sperm with lower nuclear
      vacuolization and presumably lower DNA fragmentation than the whole ejaculate.
      CONCLUSION(S): Swim-up produces samples with less vacuolization, but the recovery
      rate is also lower. The choice of processing technique would then depend on
      whether intrauterine insemination, IVF or ICSI/IMSI is to be performed. A
      prospective randomized study scoring fertility rates would be necessary to
      directly access the influence of these methods on the fertility outcome.

PMID- 20674903
TI  - Dynamics of early estradiol production may be associated with outcomes of in
      vitro fertilization.
AB  - This study investigated the effects of total E(2) production during controlled
      ovarian stimulation (COS) calculated by "modified area under the curve for E(2)
      (AUC-E(2))" and of the changes in E(2) level during the initial stimulation
      period calculated as "slope of initial increase in E(2) (Sl-E(2))" on the
      outcomes of IVF cycles using GnRH antagonist protocols. The findings suggest that
      the rate of initial increase in E(2) rather than total E(2) production during COS
      might affect the competence of retrieved oocytes in GnRH antagonist cycles.

PMID- 20674904
TI  - Abnormal sperm count and motility on semen analysis are not sufficiently
      predictive of abnormal Kruger morphology.
AB  - Abnormal morphology by Kruger's strict criteria cannot be predicted reliably by
      the presence of other abnormal parameters on semen analysis. Assessment of Kruger
      morphology therefore remains a necessary component of a complete semen analysis
      in the workup of the infertile couple.

PMID- 20674905
TI  - Pregnancies and deliveries after injection of vitrified-warmed oocytes with
      cryopreserved testicular sperm.
AB  - The purpose of this study is to report successful pregnancies and deliveries from
      embryos derived from vitrified-warmed oocytes injected with frozen-thawed
      testicular sperm. After the vitrification-warming procedure, surviving oocytes
      from 11 patients were microinjected with thawed testicular spermatozoa, and
      subsequent viable cleaving embryos were transferred, resulting in four clinical
      pregnancies.

PMID- 20674906
TI  - Anti-implantation effect of 2-[piperidinoethoxyphenyl]-3-[4-hydroxyphenyl]-2H
      benzo(b)pyran, a potent antiestrogenic agent in rats.
AB  - OBJECTIVE: To investigate the anti-implantation effect and hormonal profile of 2
      [piperidinoethoxyphenyl]-3-[4-hydroxyphenyl]-2H-benzo(b)pyran (K-1) in rats.
      DESIGN: In vivo assays for anti-implantation activity were performed in pregnant
      rats. Assays for estrogenicity/antiesrogenicity were performed in immature
      ovariectomized female rats. In vitro competitive binding of K-1 to human
      recombinant ERalpha, transient transfection assay using ERE-luciferase reporter,
      and alkaline phosphatase (ALP) activity as a measure of estrogenicity
      and/antiestrogenicity in human endometrial carcinoma cells were performed.
      SETTING: Research laboratory. ANIMAL(S): Adult female rats for anti-implantation
      activity, immature ovariectomized female rats, and immature castrated/intact male
      rats. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Number of implantations,
      uterine growth, luciferase reporter activity, ER binding affinity, and ALP
      activity. RESULT(S): Compound K-1 given orally for 1-7 days post coitum at the
      dose of 100 MUg/kg body weight prevented pregnancy in 100% of rats. K-1 was a
      potent antiestrogenic, and at 50 MUg/kg, it could inhibit the effect of 1 MUg
      E(2) in immature rats. Compound was devoid of uterotrophic, androgenic, or
      antigonadotropic activity. A high affinity binding to ERalpha was displayed by K
      1, with a relative binding affinity of 5% of E(2). In human endometrial carcinoma
      cells, K-1 did not induce ERalpha-mediated transcriptional activation that is
      measured as luciferase reporter activity. K-1 antagonized the E-induced
      transcriptional activation significantly. K-1 also antagonized E-induced ALP
      activity in human endometrial cells. CONCLUSION(S): K-1 appeared to exert its
      antifertility action by virtue of its strong antiestrogenic activity.

PMID- 20674907
TI  - Race, socioeconomic status, and response to methotrexate treatment of ectopic
      pregnancy in an urban population.
AB  - On the basis of the documented racial disparities in ectopic pregnancy incidence
      and mortality we hypothesized that African-American women with ectopic pregnancy
      would be more likely than white women to have treatment failure with
      methotrexate. In this retrospective cohort study, a racial disparity in
      methotrexate effectiveness was not found, but a significant relationship between
      low socioeconomic status and methotrexate failure was demonstrated.

PMID- 20674908
TI  - A giant oocyte in a cohort of retrieved oocytes: does it have any effect on the
      in vitro fertilization cycle outcome?
AB  - OBJECTIVE: To investigate an association between the presence of a giant oocyte
      and outcome for the cohort in in vitro fertilization (IVF). DESIGN: Retrospective
      study. SETTING: Hospital-based academic medical center. PATIENT(S): IVF and
      IVF/intracytoplasmic sperm injection (ICSI) cycles having at least one giant
      oocyte (study group; n = 105), matched with cycles without a giant oocyte
      (external control group). A further subanalysis compared giant oocyte cycles with
      the next closest cycles within patients (internal control group; n = 65).
      INTERVENTION(S): Standard IVF protocols. MAIN OUTCOME MEASURE(S): Incidence of
      giant oocytes, fertilization rate, quality of cohort embryos, and pregnancy
      outcome. RESULT(S): Out of 97,556 oocytes, 117 (0.12%) were giant. Compared with
      the external control group, cleavage in the study group was abnormal (increased
      percentage of 1-cell and 10-cell embryos and decreased percentage of 6-cell and 7
      cell embryos), although there was no difference for percentage of embryos with
      perfect symmetry, fragmentation, or implantation, clinical pregnancy, or
      ongoing/delivered rate. The study group had two cases of pregnancy termination
      due to chromosomal abnormalities (4.4%) versus none in external controls. No
      striking differences in embryo quality existed between the study and internal
      control groups. CONCLUSION(S): A giant oocyte is associated with abnormal
      cleavage in cohort embryos, but not with implantation or pregnancy rates. Giant
      oocytes occur sporadically and appear not to reflect quality of remaining oocytes
      in the ovary.

PMID- 20674909
TI  - Meiotic chromosome abnormalities in fertile men: are they increasing?
AB  - OBJECTIVE: To determine the basal frequencies of meiotic chromosome abnormalities
      in fertile men. DESIGN: Descriptive design. SETTING: Research university
      laboratory and clinical andrology service. PATIENT(S): Seventeen fertile donors
      undergoing vasectomy. INTERVENTION(S): Analysis of testicular biopsies. MAIN
      OUTCOME MEASURE(S): Meiotic chromosome abnormalities in metaphase I
      spermatocytes. RESULT(S): A total of 1,407 spermatocytes I was analyzed. The main
      meiotic abnormality was absence or low chiasma number of individual bivalents
      (23.4%), followed by structural (3.3%) and numerical (0.7%) abnormalities. Sex
      chromosomes and G-group chromosomes were the most commonly found as univalents at
      metaphase I. Statistically significant heterogeneity was found for meiotic
      abnormalities among fertile men, caused by interindividual variation in the level
      of dissociated sex chromosomes (ranging from 3.2% to 43.7%). The mean total
      percentage of meiotic abnormalities in spermatocytes I from fertile men was
      27.4%, 1.7 times higher than those described a few decades ago in fertile and
      even in infertile men. CONCLUSION(S): Fertile men are a heterogeneous group for
      meiotic errors, with individuals showing percentages of meiotic abnormalities as
      high as 50%. From these findings, caution is recommended when using meiotic
      studies to diagnose and provide genetic counselling to patients consulting for
      infertility.

PMID- 20674910
TI  - An approach to noninvasive delivery, biodistribution, and fertility control
      potential evaluation of the Cuproferrogel iron oxide-copper-styrene maleic
      anhydride-dimethyl sulphoxide in the female.
AB  - Under guidance of an external pulsed magnetic field the Cuproferrogel iron oxide
      copper-styrene maleic anhydride-dimethyl sulphoxide delivered into the rat/rabbit
      oviduct resulted in oocytes with granulated cytoplasm, zona enlargement, membrane
      disintegration, and finally loss of viability in 72 hours. Also, the percentage
      biodistribution of magnetic and electrically conductive particles observed under
      safe level advocates the use of Cuproferrogel as a potential female fertility
      control molecule.

PMID- 20674911
TI  - A comparison of the effects of three different luteal phase support protocols on
      in vitro fertilization outcomes: a randomized clinical trial.
AB  - OBJECTIVE: To evaluate the effects of three different luteal phase support
      protocols on pregnancy and implantation rates, as well as luteal phase hormone
      profile in intracytoplasmic sperm injection-ET cycles. DESIGN: A prospective,
      randomized study. SETTING: A tertiary teaching and research hospital. PATIENT(S):
      Two hundred eighty-eight patients who were undergoing intracytoplasmic sperm
      injection with a long protocol of controlled ovarian hyperstimulation.
      INTERVENTION(S): Group 1 (E(2) + P) received daily P plus 4 mg of E(2), group 2
      (hCG + P) received P plus 1,500 IU of hCG, and group 3 (P only) received daily
      vaginal P gel. Blood samples were drawn on the day of hCG administration, as well
      as 7 and 10 days after the hCG for the E(2) and P measurements. MAIN OUTCOME
      MEASURE(S): The clinical pregnancy rate. RESULT(S): No difference existed between
      the E(2) + P and hCG + P groups with respect to pregnancy rate, but it was
      significantly lower in the P-only group.The implantation rate was significantly
      lower in the P-only group than in the other groups.The highest miscarriage rate
      was in the P-only group (38%). CONCLUSION(S): In assisted reproductive technology
      cycles including treatment with GnRH agonist, adding 4 mg of oral E(2) to P
      during the luteal phase significantly increased the pregnancy and implantation
      rates and decreased the miscarriage rate compared with the use of P only.

PMID- 20674912
TI  - Association between socio-psycho-behavioral factors and male semen quality:
      systematic review and meta-analyses.
AB  - OBJECTIVE: To identify the factors associated with male semen quality from many
      socio-psycho-behavioral factors. DESIGN: Medline/PubMed, EMBASE, and CNKI were
      searched to identify relevant publications for systematic review and meta
      analysis. PATIENT(S): None. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S):
      Thirteen socio-psycho-behavioral factors in 57 cross-sectional studies with
      29,914 participants from 26 countries/regions were involved in this review. Six
      factors (age, body mass index [BMI], psychological stress, smoking, alcohol, and
      coffee consumption) were included in meta-analyses. RESULT(S): Smoking can
      deteriorate all of the sperm parameters of both fertile and infertile men, but it
      is not risk factor for semen volume in Switzerland and Iran and for sperm density
      in the United States, Denmark, and Brazil; higher age and alcohol consumption are
      risk factors for lower semen volume; and psychological stress can lower sperm
      density and sperm progressive motility and increase abnormal sperm.
      CONCLUSION(S): This review further suggested that higher age, smoking, alcohol
      consumption, and psychological stress were risk factors for semen quality. These
      results indicated that health programs focusing on lifestyle and psychological
      health would be helpful for male reproductive health. Well-designed studies are
      needed to further identify the role of more socio-psycho-behavioral factors in
      male semen quality.

PMID- 20674913
TI  - The forgotten coil.
AB  - OBJECTIVE: To raise awareness of forgotten intrauterine contraceptive devices
      (IUDs). DESIGN: Case report. SETTING: District general hospital in London.
      PATIENT(S): Two women, one with secondary infertility and one with heavy, painful
      periods, both unaware they had an IUD. INTERVENTION(S): Removal of the forgotten
      IUD. MAIN OUTCOME MEASURE(S): Return of fertility and improvement in gynecologic
      symptoms. RESULT(S): After the removal of the IUD, the first patient who had had
      secondary infertility conceived within 1 month. In the second patient, the
      symptoms of menorrhagia and dysmenorrhea improved after removal of the IUD.
      CONCLUSION(S): Although it is rare, a forgotten IUD is a potential cause of
      unexplained infertility and a differential diagnosis for gynecologic symptoms.

PMID- 20674914
TI  - Prediction of pregnancy rate by blastocyst morphological score and age, based on
      1,488 single frozen-thawed blastocyst transfer cycles.
AB  - OBJECTIVE: To present an estimation of the pregnancy rate after IVF or
      intracytoplasmic sperm injection stratified by blastocyst morphology and age.
      DESIGN: Retrospective analysis. SETTING: Private IVF clinic. PATIENT(S): A total
      of 1,488 single frozen-thawed blastocyst transfer cycles. INTERVENTION(S): All
      frozen-thawed blastocysts used in the study were obtained in the patients' first
      oocytes retrieval cycles. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate (CPR),
      viable pregnancy rate (VPR), and delivery rate (DR) according to blastocyst
      morphological score (Gardner and Schoolcraft score) in three different age
      groups: women aged 22-33 years, 34-37 years, and 38-45 years. RESULT(S): The
      quality of blastocysts degraded as age group increased. The proportions of good
      quality blastocysts (grades 4 and above) were 62.3%, 56.3%, and 41.1% in age
      groups of 22-33 years, 34-37 years, and 38-45 years. Within the same blastocyst
      quality, CPR, VPR, and DR tended to be lower with increased age. Chances of
      pregnancy were reduced by 60% or more for women 38 years and older with
      blastocyst morphology of grades 1 and 2. Significant trends were observed for
      both age and blastocyst morphology groups. CONCLUSION(S): There was a significant
      correlation between blastocyst quality and CPR, VPR, and DR in addition to the
      influence of age on the three rates. The findings may help predict successful
      pregnancy in single-blastocyst transfer.

PMID- 20674915
TI  - Unusual nontuberculous mycobacterium infection of the rectum.

PMID- 20674916
TI  - Combined contrast-enhanced power Doppler and real-time sonoelastography performed
      during EUS, used in the differential diagnosis of focal pancreatic masses (with
      videos).
AB  - BACKGROUND: Contrast-enhanced power Doppler (CEPD) and real-time sonoelastography
      (RTSE) performed during EUS were previously described to be useful for the
      differential diagnosis between chronic pseudotumoral pancreatitis and pancreatic
      cancer. OBJECTIVE: To prospectively assess the accuracy of the combination of
      CEPD and RTSE to differentiate pancreatic focal masses. DESIGN: Cross-sectional
      feasibility study. SETTING: A tertiary-care academic referral center. PATIENTS:
      The study group included 54 patients with chronic pancreatitis (n = 21) and
      pancreatic adenocarcinoma (n = 33). INTERVENTIONS: Both imaging methods (CEPD and
      RTSE) were performed sequentially during the same EUS examination. Power Doppler
      mode examination was performed after intravenous injection of a second-generation
      contrast agent (2.4 mL of SonoVue), and the data were digitally recorded,
      comprising both the early arterial phase and venous/late phase. Three 10-second
      sonoelastographic videos were also digitally recorded that included the focal
      mass and the surrounding pancreatic parenchyma. Postprocessing analyses based on
      specially designed software were used to analyze the CEPD and RTSE videos. A
      power Doppler vascularity index was used to characterize CEPD videos, the values
      being averaged during a 10-second video in the venous phase. Hue histogram
      analysis was used to characterize RTSE videos, with the mean hue histogram values
      being also averaged during a 10-second video. MAIN OUTCOME MEASUREMENTS: To
      differentiate chronic pancreatitis and pancreatic cancer. RESULTS: The
      sensitivity, specificity, and accuracy of combined information provided by CEPD
      and RTSE to differentiate hypovascular hard masses suggestive of pancreatic
      carcinoma were 75.8%, 95.2%, and 83.3%, respectively, with a positive predictive
      value and negative predictive value of 96.2% and 71.4%, respectively. LIMITATION:
      A single-center, average size of study population. CONCLUSIONS: A combination of
      CEPD and RTSE performed during EUS seems to be a promising method that allows
      characterization and differentiation of focal pancreatic masses.

PMID- 20674917
TI  - Management of an iatrogenic ileal perforation by temporary transileostomy
      placement of a fully covered esophageal self-expanding metal stent.

PMID- 20674918
TI  - Postabortion care counseling practiced by health professionals in southeastern
      Nigeria.
AB  - OBJECTIVE: To determine the practice of postabortion care (PAC) counseling among
      healthcare professionals in southeastern Nigeria. METHODS: A cross-sectional
      questionnaire-based survey conducted among healthcare professionals in Anambra
      State, southeastern Nigeria, in 2006. Participants were chosen using a multi
      stage sampling technique. A pre-tested questionnaire assessing the practice of
      PAC counseling was administered. RESULTS: A total of 431 health professionals
      were questioned: 270 (62.6%) medical doctors and 161 (37.4%) nurses. Of 302
      (70.1%) respondents who reported practicing PAC counseling, only 173 (40.1%) had
      received formal training. PAC counseling was most commonly practiced by health
      professionals working in the University Teaching Hospital (90.5%). It was also
      more commonly practiced by nurses in rural areas compared with nurses working in
      urban areas (75 [67.6%] vs 24 [48.0%]; P=0.02). CONCLUSION: A high proportion of
      health professionals reported practicing PAC counseling. However, less than half
      had received formal training in PAC counseling. An increased PAC training
      activity program, with an emphasis on counseling, is recommended for health
      professionals to improve the overall quality of PAC service delivery.

PMID- 20674919
TI  - Screening for cervical neoplasia in Bangladesh using visual inspection with
      acetic acid.
AB  - OBJECTIVE: To report the organization and early results of a visual inspection
      with acetic acid (VIA) screening program for cervical cancer prevention in
      Bangladesh. METHODS: Opportunistic VIA screening was offered by trained medical
      personnel to healthy women attending healthcare facilities in 44 districts.
      Colposcopy and/or directed biopsies were performed on VIA-positive women at
      Bangabandhu Sheikh Mujib Medical University (BSMMU) or medical college hospitals.
      The numbers of screened and VIA-positive women as well as the results of
      colposcopy, biopsy, and treatment of those with cervical intraepithelial
      neoplasia (CIN) attending BSMMU are reported. RESULTS: From January, 2005, to
      June, 2008, 104098 women underwent VIA screening. Among them, 5013 (4.8%) women
      were positive, of whom 4371 (87.2%) attended colposcopy clinics in different
      hospitals. Of the 2188 who underwent colposcopy at BSMMU, 157 were diagnosed with
      CIN 2-3 and 123 with invasive cancer. For 2065 women (excluding the cancer
      cases), results for sensitivity, specificity, and positive predictive value of
      VIA to detect CIN 2-3 lesions were 93.6%, 58.3%, and 15.6%, respectively. Almost
      half the women with CIN 2 or 3 lesions had treatment. CONCLUSION: A VIA-based
      program would facilitate the development of screening, diagnosis, and treatment
      of cervical neoplasia and improve awareness of cervical cancer prevention in
      Bangladesh.

PMID- 20674920
TI  - Characterizing gait induced normal strains in a murine tibia cortical bone defect
      model.
AB  - The critical role that mechanical stimuli serve in mediating bone repair is
      recognized but incompletely understood. Further, previous attempts to understand
      this role have utilized application of externally applied mechanical loads to
      study the tissue's response. In this project, we have therefore endeavored to
      capitalize on bone's own consistently diverse loading environment to develop a
      novel model that would enable assessment of the influence of physiologically
      engendered mechanical stimuli on cortical defect repair. We used an inverse
      dynamics approach with finite element analysis (FEA) to first quantify normal
      strain distributions generated in mouse tibia during locomotion. The strain
      environment of the tibia, as previously reported for other long bones, was found
      to arise primarily due to bending and was consistent in orientation through the
      stance phase of gait. Based on these data, we identified three regions within a
      transverse cross-section of the mid-diaphysis as uniform locations of either peak
      tension, peak compression, or the neutral axis of bending (i.e. minimal strain
      magnitude). We then used FEA to quantify the altered strain environment that
      would be produced by a 0.6mm diameter cylindrical cortical bone defect at each
      diaphyseal site and, in an in situ study confirmed our ability to accurately
      place defects at the desired diaphyseal locations. The resulting model will
      enable the exploration of cortical bone healing within the context of
      physiologically engendered mechanical strain.

PMID- 20674921
TI  - The influence of altering push force effectiveness on upper extremity demand
      during wheelchair propulsion.
AB  - Manual wheelchair propulsion has been linked to a high incidence of overuse
      injury and pain in the upper extremity, which may be caused by the high load
      requirements and low mechanical efficiency of the task. Previous studies have
      suggested that poor mechanical efficiency may be due to a low effective handrim
      force (i.e. applied force that is not directed tangential to the handrim). As a
      result, studies attempting to reduce upper extremity demand have used various
      measures of force effectiveness (e.g., fraction effective force, FEF) as a guide
      for modifying propulsion technique, developing rehabilitation programs and
      configuring wheelchairs. However, the relationship between FEF and upper
      extremity demand is not well understood. The purpose of this study was to use
      forward dynamics simulations of wheelchair propulsion to determine the influence
      of FEF on upper extremity demand by quantifying individual muscle stress, work
      and handrim force contributions at different values of FEF. Simulations
      maximizing and minimizing FEF resulted in higher average muscle stresses (23% and
      112%) and total muscle work (28% and 71%) compared to a nominal FEF simulation.
      The maximal FEF simulation also shifted muscle use from muscles crossing the
      elbow to those at the shoulder (e.g., rotator cuff muscles), placing greater
      demand on shoulder muscles during propulsion. The optimal FEF value appears to
      represent a balance between increasing push force effectiveness to increase
      mechanical efficiency and minimize upper extremity demand. Thus, care should be
      taken in using force effectiveness as a metric to reduce upper extremity demand.

PMID- 20674922
TI  - Determination of joint moments with instrumented force shoes in a variety of
      tasks.
AB  - Ground reaction forces (GRFs) are often used in inverse dynamics analyses to
      determine joint loading. These GRFs are usually measured using force plates
      (FPs). As an alternative, instrumented force shoes (FSs) can be used, which have
      the advantage over FPs that they do not constrain foot placement. This study
      tested the FS system in one normal weight subject (77kg) performing 19 different
      lifting, pushing and pulling and walking tasks. Kinematics were measured with an
      optoelectronic system and the GRFs and the positions of the centre of pressure
      (CoP) were synchronously measured with FPs and FSs. Differences between the
      outcomes of the two measurement systems (i.e. CoP and GRFs) and the resulting
      ankle and L5/S1 joint moments were determined at the instant of the peak GRF
      (DaPF). For most lifting and pushing and pulling tasks, the difference between
      the FP and FS measurements remained small: GRF DaPF remained below 3% body
      weight, CoP DaPF remained below 10mm, ankle moment DaPF remained below 7% of the
      peak total ankle moment that occurred during normal walking and L5/S1 moment DaPF
      remained below 7% of the peak total L5/S1 moment that occurred during normal
      symmetric lifting. More substantial differences were only found in the maximal
      pushing tasks. For the walking tasks, peak vertical GRFs were somewhat
      underestimated. However, differences in ankle and L5/S1 moments remained small,
      i.e. DaPF below 7% of the peak total moment that occurred during normal walking.

PMID- 20674923
TI  - The relationship between gap formation and grip-to-grip displacement during
      cyclic testing of repaired flexor tendons.
AB  - The assessment of repair site gap formation during cyclic loading of
      reconstructed flexor tendons provides important data on the performance of repair
      techniques in the early postoperative period. This study describes our cyclic
      testing protocol and evaluates the relationship between changes in optical gap
      and grip-to-grip displacement. Sixteen sheep hind limb deep flexor tendons were
      randomized into four repair groups (n=4 per group): a 2-strand repair (modified
      Kessler) and 4-strand repair (Adelaide), both with and without a simple running
      peripheral suture. Repaired tendons were cycled for 1000 cycles at appropriate
      rehabilitation loads for the reconstruction. Tendons were paused at 18 pre
      determined cycle points to measure gap and displacement. A strong positively
      linear relationship between gap and displacement was demonstrated for all repair
      groups (R2>0.90). An initial non-linear region during the first 10 cycles was
      noted with some combined core and peripheral repairs. Although trends in
      displacement after 10 cycles can be used to reflect gapping behaviour, direct
      optical measurement of gap remains preferable. We hypothesized that the
      adjustment of suture strands and equilibration of forces within the
      reconstruction occurs mostly during the initial 10 cycles. Gap-cycle curves
      provide a good illustration of dynamic changes at the repair site, and should be
      added more frequently to cyclic testing studies.

PMID- 20674924
TI  - Silica-based monolithic capillary columns-Effect of preparation temperature on
      separation efficiency.
AB  - The temperature effects during the sol-gel process and ageing of the silica-based
      monolith on the structure and separation efficiency of the capillary columns
      (100microm i.d., 150mm) for HPLC separations were studied. The tested columns
      were synthesized from a mixture of tetramethoxysilane, polyethylene glycol and
      urea under the acidic conditions. The temperature was varied from 40 degrees C to
      44 degrees C and formation of bypass channels between the silica mold and the
      capillary wall was examined. The temperature of 43 degrees C was estimated as
      optimal for preparation of efficient silica capillary columns which were
      subsequently modified by octadecyldimethyl-N,N-diethylaminosilane or covered by
      poly(octadecyl methacrylate) and tested using standard mixture of alkylbenzenes
      under the isocratic conditions.

PMID- 20674925
TI  - Evaluation of eggshell membrane-based bio-adsorbent for solid-phase extraction of
      linear alkylbenzene sulfonates coupled with high-performance liquid
      chromatography.
AB  - The potential of eggshell membrane (ESM) as a novel solid-phase extraction bio
      adsorbent was investigated in the present study. The ESM with a unique structure
      of intricate lattice network showed a predominant ability to capture linear
      alkylbenzene sulfonates (LAS) as a model of organic pollutants by the hydrophobic
      interactions between ESM and LAS molecular at pH very close to the isoelectric
      point of ESM, which was similar to the most widely used trapping mechanism for
      SPE. Under the optimal conditions, the breakthrough capacities of the ESM packed
      cartridge for C10-C13 LAS homologues were found to be 30, 53, 50, and 43microgg(
      1), respectively. On the basis of high-performance liquid chromatography
      separation and UV detection of LAS homologues, the proposed system could respond
      down to 0.027ngmL(-1) of LAS with a linear calibration range from 0.2 to 100ngmL(
      1), showing a good LAS enrichment ability of eggshell membrane biomaterial with
      high sensitivity, and could be successfully used for the detection of residual
      LAS in environmental water samples. The reproducibility among columns was
      satisfactory (RSD among columns is less than 10%). A comparison study with ESM,
      C8 and C18 as adsorbents for LAS demonstrated that ESM-based bio-adsorbent was
      advantageous over C8 and C18, the widely used traditional adsorbents.

PMID- 20674926
TI  - Determination of intracellular sulphydryl compounds by microchip electrophoresis
      with selective chemiluminescence detection.
AB  - An analytical method based on microchip electrophoresis (MCE) and
      chemiluminescence detection (CL) was developed for the determination of
      intracellular sulphydryl compounds. Cell injection/loading, cytolysis,
      electrophoretic separation, and CL detection were integrated onto a simple cross
      microfluidic chip. Selective CL detection of sulphydryl compounds was achieved by
      deploying the luminol-Na(2)S(2)O(8) reaction. Under the CL conditions selected,
      many endogenous compounds in biological systems such as amino acids, biogenic
      amines, peptides and proteins did not produce any CL signal, which further
      ensured a high selectivity of the proposed MCE-CL assays. Sulphydryl compounds
      including cysteine (Cys), glutathione (GSH), and hemoglobin (Hb) were selected as
      the test compounds. The MCE separation was completed within 120s. The detection
      limits were estimated to be 7amol for Cys, 32amol for GSH and 69amol for Hb,
      respectively. The present method was applied to analyze individual red blood
      cells collected from both healthy subjects and cancer patients. It was found that
      the average intracellular contents of Cys, GSH and Hb were in the ranges of 26
      43amol/cell, 128-323amol/cell and 522-667amol/cell, respectively for cancer
      patients, compared to 579-609amol Hb/cell and not detectable Cys and GSH for
      healthy subjects.

PMID- 20674927
TI  - Mesoporous silicate MCM-48 as an enrichment medium for ambient volatile organic
      compound analysis.
AB  - This study investigated the sorption/desorption properties of MCM-48 and its
      applicability as a sorbent for on-line gas chromatographic analysis of ambient
      volatile organic compounds (VOCs). To establish a valid comparison, commercially
      available carbon sorbents were evaluated under similar analytical conditions. Two
      trapping temperatures of 30 degrees C and -20 degrees C, representing ambient and
      sub-ambient temperatures, were tested by trapping a full range of VOCs from C(2)
      C(12). At ambient temperatures, due to the mesoporosity, the MCM-48 showed
      considerably limited trapping efficiency compared to microporous carbon sorbents
      on the highly volatile section of VOCs and only began to show effective trapping
      for compounds larger than C(7). Cooling to sub-ambient temperatures (e.g., -20
      degrees C) extended the effective trapping down to C(4) VOCs, drastically
      increasing the applicability of MCM-48 as an in-line enrichment medium for gas
      chromatographic analysis of VOCs. The mesoporosity of MCM-48 also aided
      desorption. Much lower desorption temperatures (100-180 degrees C) were required
      for full desorption as compared to the temperatures (greater than 200 degrees C)
      required for carbon sorbents. Moreover, the easy desorption was accompanied by a
      low memory effect, as the large pores of MCM-48 can clean up more efficiently
      after desorption, with little residue left behind.

PMID- 20674928
TI  - Self-assembly of beta-cyclodextrin and pluronic into hollow nanospheres in
      aqueous solution.
AB  - This paper studies self-assembly of beta-cyclodextrin (beta-CD) and tri-block
      pluronic (PEG-PPG-PEG) in aqueous solution. It was found that they could form
      hollow spheres due to the formation of coil-rod beta-CD/PEG-PPG-PEG inclusion
      complexes. In these beta-CD/PEG-PPG-PEG complexes, the beta-CDs are
      preferentially stacked along the PPG block of pluronic to form rod block and PEG
      segments act as coil block. The assemblies of beta-CD/PEG-PPG-PEG complexes show
      dependence of beta-CDs concentration and temperature. Furthermore, the aggregates
      will disrupt upon dilution below the critical micelle concentration.

PMID- 20674930
TI  - Automatic shifts of attention in the Dimensional Change Card Sort task: subtle
      changes in task materials lead to flexible switching.
AB  - Two experiments tested a hypothesis that reducing demands on executive control in
      a Dimensional Change Card Sort task will lead to improved performance in 3-year
      olds. In Experiment 1, the shape dimension was represented by two dissimilar
      values (stars and flowers), and the color dimension was represented by two
      similar values (red and pink). This configuration of stimuli rendered shape more
      salient than color. In Experiment 2, attentional weights of each dimension value
      were manipulated by using two versus four values to represent the dimensions of
      shape and color. The results indicated that increasing saliency of the postswitch
      dimension (Experiment 1) and reducing attentional weights of individual dimension
      values (Experiment 2) lead to a marked improvement in the postswitch sorting
      accuracy in 3-year-olds.

PMID- 20674929
TI  - Stability and composition of functional synergies for speech movements in
      children with developmental speech disorders.
AB  - The aim of this study was to investigate the consistency and composition of
      functional synergies for speech movements in children with developmental speech
      disorders. Kinematic data were collected on the reiterated productions of
      syllables spa(/spa?/) and paas(/pa?s/) by 10 6- to 9-year-olds with developmental
      speech disorders (five with speech sound disorder [SSD] and five with subtype
      childhood apraxia of speech [CAS]) and six normally speaking children using
      electro-magnetic midsagittal articulography (EMMA). Results showed a higher
      variability of tongue tip movement trajectories and a larger contribution of the
      lower lip relative to the jaw in oral closures for the five children with CAS
      compared to normally developing controls, indicating that functional synergies
      for speech movements in children with CAS may be both delayed and less stable.
      Furthermore, the SSD group showed a composition of tongue tip movements that is
      different from both CAS and controls. These results suggest that the differences
      in speech motor characteristics between SSD and subtype CAS are qualitative
      rather than quantitative. At the same time, the results suggest that both SSD and
      subtype CAS increase movement amplitude as an adaptive strategy to increase
      articulatory stability. Although in direct comparison no exclusive
      characteristics were found to differentiate subtype CAS from the group of
      children with SSD and from normally developing children, these preliminary
      results are promising for quantifying the role of speech motor processes in
      childhood speech sound disorders. LEARNING OUTCOMES: The reader will be able to:
      (1) describe the development of speech motor control and explain the role of
      functional synergies/coordinative structures; (2) explain the measurement of the
      stability and composition of speech movements; (3) identify the difficulties in
      studying disordered speech motor development; (4) describe the differences in
      speech motor characteristics between SSD and subtype CAS; (5) describe the
      potential role of motor control strategies in developmental speech disorders.

PMID- 20674931
TI  - School entry age outcomes for infants with birth weight <= 800 grams.
AB  - OBJECTIVE: To evaluate the mortality and long-term morbidity rates of extremely
      low birth weight (ELBW) infants admitted to neonatal intensive care units
      (NICUs). STUDY DESIGN: This was a longitudinal cohort study of all admissions
      born between 1983 and 2003 with birth weight <= 800 g at a single tertiary NICU.
      Trends in survival and neurodevelopmental outcome rates at school entry in four 5
      year epochs were analyzed. RESULTS: Of 917 admissions, 552 survived to NICU
      discharge, with significantly increasing survival rates from 46% in epoch 1 to
      71% in epoch 4 (P < .0001). Although the overall impairment rate of 30% did not
      change, the pattern of impairments did. Cognitive (P = .017) and hearing (P =
      .014) impairment rates increased. Visual impairment rates decreased (P = .042),
      with a trend toward decreasing cerebral palsy from 20% to 12% (P = .061).
      CONCLUSIONS: Improved survival of low birth weight preterm infants has been
      associated with different types of neurodevelopmental impairments, including
      increased cognitive impairment rates.

PMID- 20674932
TI  - Systolic blood pressure contributes to intracerebral haemorrhage after
      thrombolysis for ischemic stroke.
AB  - The frequency and risk factors for intracerebral haemorrhage (ICH) after ischemic
      stroke are well-known. ICH frequency is increased by the use of antithrombotic or
      thrombolytic drugs. Several experimental studies have demonstrated a relationship
      between ICH and hypertension after fibrinolysis, but the optimal blood pressure
      levels in patients treated with recombinant tissue plasminogen activator (rTPA)
      are as yet unknown. We evaluated the role of blood pressure in patients with
      ischemic stroke treated with rTPA within 3h of symptom onset. We treated 86
      consecutive patients admitted to our stroke unit between 2002 and 2008 and
      prospectively recorded the clinical and instrumental data in our stroke registry.
      We evaluated haemorrhagic complications by reviewing imaging findings. Blood
      pressure was recorded before rTPA and at 6, 12, 18, and 32h. Total cerebral
      haemorrhage occurred in eleven (12.7%) patients, and symptomatic intracerebral
      haemorrhage occurred in seven (8.1%). We failed to find a correlation between
      blood pressure levels and stroke severity at admission. High blood pressure
      levels correlated with a worse outcome. Systolic blood pressure was significantly
      higher in ICH patients relative to rTPA-treated patients without haemorrhagic
      complications (p<0.03). This study indicates that rTPA-induced haemorrhage is
      influenced by systolic blood pressure. More aggressive pharmacological reduction
      of hypertension during fibrinolysis and the subsequent 32h may reduce this
      complication.

PMID- 20674933
TI  - High levels of serum uric acid are associated with silent brain infarction.
AB  - BACKGROUND: Uric acid has been known to exert neuroprotective effects by acting
      as a free radical scavenger; however, several observational studies indicated
      that high levels of serum uric acid increased the risk of cardiovascular events
      or stroke. We sought to determine whether increased levels of uric acid are
      associated with the presence of silent brain infarction (SBI). METHODS: We
      recruited a consecutive series of non-stroke individuals who visited the
      Healthcare System in our hospital and underwent brain MRI (n=1577). We conducted
      intensive interviews and laboratory examinations, including serum uric acid. We
      examined associations between SBI and vascular risk factors including uric acid
      by controlling possible confounders. RESULTS: Of the 1577 subjects recruited, 921
      were men and 656 were women, and the uric acid level was much higher in the men
      (6.3+/-1.3) than in the women (4.7+/-1.0). There was a strong dose-response
      relationship between the quartiles of uric acid and the presence of SBI in women
      (p=0.001), but not in men. Multivariable analysis showed that the highest
      quartile of uric acid level was an independent risk factor for the presence of
      SBI in total patients (adjusted OR, 1.79; 95% CI, 1.11-2.91). However, this
      association remained significant in women (adjusted OR, 2.64; 95% CI, 1.17-5.91),
      but not in men. CONCLUSIONS: Our results suggest that an increased level of uric
      acid may be a risk factor for the presence of SBI. Serum uric acid level might be
      a good serum marker of underlying SBI or future stroke, especially in women.

PMID- 20674934
TI  - Frontotemporal lobar degeneration with motor neuron disease showing severe and
      circumscribed atrophy of anterior temporal lobes.
AB  - Frontotemporal lobar degeneration (FTLD) is characterized by a variety of
      behavioral and psychiatric symptoms based on the dysfunction of frontal and/or
      temporal lobes. A 63-year-old Japanese man without a family history of
      neurological diseases developed progressive symptoms of frontotemporal dementia,
      followed by motor neuron disease (MND). Brain magnetic resonance images
      demonstrated severe atrophy in the anterior temporal lobes from early clinical
      stage. The symptoms got rapidly worsened and the patient died of respiratory
      failure 1year 8months after the disease onset. A postmortem study revealed severe
      and circumscribed atrophy in the anterior temporal lobes, and histological
      examination disclosed marked neuronal loss with many neuronal cytoplasmic
      inclusions which were immunoreactive for ubiquitin antibodies and phosphorylated
      TAR DNA-binding protein of 43kDa (TDP-43) antibodies in hippocampal dentate
      granule cells and amygdalae, as well as a few neuronal cytoplasmic inclusions
      without dystrophic neurites in the temporal neocortex. This case report showed
      typical features of FTLD-MND in clinical course and TDP-43 pathology with unusual
      severity and distribution of cerebral atrophy, suggesting a unique manifestation
      of FTLD-MND.

PMID- 20674935
TI  - Adult or late-onset triple A syndrome: case report and literature review.
AB  - Triple A syndrome is caused by mutations in the gene encoding ALADIN, leading to
      achalasia, alacrima and addisonism. Neurologic manifestations of the disease
      include motor neuron disease-like presentations, motor-sensory or autonomic
      neuropathy, optic atrophy, cerebellar ataxia, Parkinsonism, and mild dementia. We
      report a 60-year-old Japanese man with triple A syndrome. He was born to non
      consanguineous parents. He underwent a surgical operation for achalasia at age
      40, and thereafter, he developed a slowly progressive gait disturbance.
      Neurological examinations at age 60 revealed limb muscle wasting and weakness
      with pyramidal tract signs, distal-dominant sensory disturbance, optic atrophy,
      and autonomic dysfunction. Alacrima was detected using Schirmer test. All of
      these features were consistent with typical triple A syndrome. He lacked adrenal
      insufficiency that is frequently observed in patients with the classic phenotype
      of triple A syndrome. His sural nerve biopsy showed a moderate loss of myelinated
      fibers and hypomyelination. He was homozygous for a missense mutation, p.R155H,
      in the disease-causing gene, AAAS. Seven patients with genetically-confirmed,
      adult or late-onset triple A syndrome, including ours, have been reported to
      date. All the patients showed upper and lower motor neuron signs (100%), while
      sensory disturbance (29%) and autonomic dysfunction (57%) were less frequent.
      Careful assessment for alacrima followed by molecular genetic analysis of AAAS
      should be considered in patients who show a combined phenotype of motor neuron
      disease and sensory/autonomic disturbance, even in elderly patients.

PMID- 20674936
TI  - An atypical case of neuro-Whipple: Clinical presentation, magnetic resonance
      spectroscopy and follow-up.
AB  - We report a case of a 53-year-old man with a 2-year history of progressive gait
      and balance disturbance, supranuclear ophthalmoparesis, mild dysarthria and
      dysmetria. EMG revealed a lower limb axonal sensory-motor neuropathy, while MR
      imaging demonstrated a small focal lesion in the right frontal lobe, mild diffuse
      hyperintensity of the periventricular white matter and diffuse brain atrophy.
      Magnetic resonance spectroscopy revealed a mild decrease in N-acetyl-aspartate
      peak and an increase in the choline peak in the small right frontal lesion and
      within 6 voxels of interest in normal appearing cerebral tissue. According to the
      clinical picture the diagnosis of WD was made by the positivity of PCR for T.
      whipplei DNA on CSF. After treatment the patient showed a mild clinical
      improvement although MR images and laboratory test remained unchanged. The MRS
      findings suggest that the pathological process of the disease diffusely involves
      the brain. Despite the absence of gastrointestinal involvement WD should be
      suspected in all complex and atypical neurological pictures, even in presence of
      peripheral involvement, in order to be able to start treatment promptly.

PMID- 20674937
TI  - Pulmonary valve replacement in repaired tetralogy of Fallot by left thoracotomy
      avoid ascending aorta injury.

PMID- 20674938
TI  - Fetal surgical management of congenital heart block in a hydropic fetus: lessons
      learned from a clinical experience.

PMID- 20674939
TI  - Surgical pitfalls of excising an intramyocardial lipoma.

PMID- 20674940
TI  - Selective antegrade cerebral perfusion during aortic arch surgery confers
      survival and neuroprotective advantages.
AB  - OBJECTIVE: To assess the impact of using antegrade cerebral perfusion during
      aortic arch surgery on postoperative survival and neurologic outcomes. METHODS:
      All operations were performed at the same hospital between January 2001 and
      January 2009. Patients undergoing aortic arch surgery using antegrade cerebral
      perfusion during deep hypothermia were compared with patients undergoing aortic
      arch surgery without antegrade cerebral perfusion during the same study period.
      Multivariable logistic regression and Cox proportional hazards model were used to
      identify predictors of postoperative cerebrovascular accidents and midterm
      survival, respectively. There were 46 patients in the antegrade cerebral
      perfusion group and 78 patients in the non-antegrade cerebral perfusion group.
      RESULTS: There were no statistically significant differences in age, proportion
      of emergency operations, or proportion of type A aortic dissection between the 2
      groups. There was a statistically significant and clinically important difference
      in the rates of postoperative cerebrovascular complications (2% antegrade
      cerebral perfusion vs 13% non-antegrade cerebral perfusion, P = .03),
      postoperative duration of mechanical ventilation (1.15 +/- 0.19 days antegrade
      cerebral perfusion vs 2.13 +/- 0.38 days non-antegrade cerebral perfusion, P =
      .02), and 3-year survival (93% antegrade cerebral perfusion vs 78% non-antegrade
      cerebral perfusion, P = .03). Antegrade cerebral perfusion was shown to be a
      significant predictor of reduced postoperative stroke rates and better survival
      at 3 years. CONCLUSIONS: Antegrade cerebral perfusion was associated with
      improved survival and neurologic outcomes in patients undergoing aortic arch
      surgery, especially for cases requiring prolonged aortic arch repair periods.

PMID- 20674941
TI  - Aortic dissection and rupture in adolescents after tetralogy of Fallot repair.

PMID- 20674942
TI  - Composite reconstruction with cryopreserved fascia lata, single mandibular
      titanium plate, and polyglactin mesh after redo surgery and radiation therapy for
      recurrent chest wall liposarcoma.

PMID- 20674944
TI  - Salvage surgery for advanced non-small cell lung cancer after response to
      gefitinib.

PMID- 20674945
TI  - Sutureless aortic valve replacement with the Trilogy Aortic Valve System:
      multicenter experience.
AB  - OBJECTIVE: To evaluate the modular sutureless Arbor Trilogy Aortic Valve System
      (Arbor Surgical Technologies, Irvine, Calif), designed for minimally invasive
      aortic valve replacement. METHODS: In a prospective multicenter study, 32
      patients with severe aortic valve stenosis underwent aortic valve replacement
      with the Trilogy valve between 2006 and 2008. Concomitant coronary artery bypass
      grafting was performed in 6 patients. Transthoracic echocardiography was
      performed at baseline, at discharge, at 4 to 6 months, at 11 to 14 months, and
      annually thereafter. RESULTS: Valve implantation was successful in 30 patients.
      The procedure was converted to conventional aortic valve replacement in 2
      patients. Mean bypass time was 111 +/- 42 minutes, and crossclamp time was 70 +/-
      23 minutes. Valve implantation took 21 +/- 7 minutes. The transvalvular gradients
      at discharge were 10 +/- 3 mm Hg (mean) and 20 +/- 7 mm Hg (peak), and the
      effective orifice area was 1.9 +/- 0.4 cm(2). At 2-year follow-up, gradients were
      7 +/- 3 mm Hg (mean) and 14 +/- 4 mm Hg (peak), and the effective orifice area
      was 1.9 +/- 0.3 cm(2). There was no intraoperative mortality: Two patients died
      of causes unrelated to the valve during follow-up. One redo aortic valve
      replacement was performed at 22 months for prosthetic valve endocarditis.
      CONCLUSIONS: Sutureless aortic valve replacement is feasible and safe with the
      Trilogy System. After an initial learning curve, the modular valve design allows
      a more rapid and simple implantation compared with conventional stented tissue
      valves. The simplicity may also facilitate a greater adoption of minimally
      invasive aortic valve replacement by a broader spectrum of surgeons.

PMID- 20674946
TI  - Magellanic penguin mortality in 2008 along the SW Atlantic coast.
AB  - Magellanic penguins migrate from Patagonia reaching northern Argentina, Uruguay,
      and southern Brazil on their winter migration, in parallel with the seasonal
      pulse of anchovy spawning. In 2008, Magellanic penguins went further north than
      usual. Many died and a few swam nearly to the Equator. Twelve groups surveyed
      5000 km of coastline encountering 3371 penguins along the coast. Most penguins
      arrived in northern Brazil (68.4%) without petroleum (2933, 87%). Almost all
      penguins without petroleum were juveniles (2915, 99%) and 55% were alive when
      found. Penguins were dehydrated, anemic, hypothermic, and emaciated. Of the
      penguins with petroleum, 13% arrived in the southern half of Brazil, showing that
      petroleum pollution remains a problem along the SW Atlantic coast. The mortality
      occurred in the winter of 2008 when sea surface temperature were unusually cold
      perhaps reducing the prey for penguins.

PMID- 20674947
TI  - Characterizing the diversity of coral reef habitats and fish communities found in
      a UNESCO World Heritage Site: the strategy developed for Lagoons of New
      Caledonia.
AB  - Since 1972, the UNESCO "World Heritage Convention" offers an international canvas
      for conservation and management that targets areas of high cultural and
      environmental significance. To support the designation of areas within the 36.000
      km(2) of New Caledonia coral reefs and lagoons as a World Heritage Site, the
      natural value and diversity of the proposed zones needed to be demonstrated. To
      exhaustively identify each configuration of shallow habitats, high resolution
      remote sensing images were used to select the sampling sites. This optimal scheme
      resulted in the selection of nearly 1300 sampling sites, and was then simplified
      to render its application realistic. In the final sampling plan, only the most
      common or the most remarkable coral zones were selected. Following this
      selection, in situ habitat and fish surveys were conducted in 2006-2008 in five
      large areas spanning a 600 km-long latitudinal gradient. Habitats were described
      using line-intercept transects in parallel with underwater visual census of
      indicator and commercial coral reef fish species. We report here on the results
      achieved in terms of: (i) the actual diversity of coral habitats captured by the
      remote sensing based sampling strategy, (ii) the different reef fish communities
      captured from the different sites, and (iii) how well they represent New
      Caledonia diversity. We discuss the possible generalization of this scheme to
      other sites, in the context of World Heritage Site selection and for other large
      scale conservation planning activities.

PMID- 20674948
TI  - Exercise training in ovariectomized rats stimulates estrogenic-like effects on
      expression of genes involved in lipid accumulation and subclinical inflammation
      in liver.
AB  - We hypothesized that the reduction in liver fat accumulation known to occur with
      exercise training in ovariectomized (Ovx) rats is associated with reduced
      expression of genes involved in lipogenesis while favoring the expression of
      transcription factors regulating lipid oxidation. We also tested the hypothesis
      that liver fat accumulation in Ovx rats is associated with an increased gene
      expression of several inflammatory biomarkers and that exercise training would
      attenuate this response. Sprague-Dawley female rats (14 weeks of age) were
      randomly divided into 4 groups of sedentary sham-operated (Sham), Ovx, Ovx with
      17beta-estradiol (E2) supplementation using a pellet (0.72 mg; 0.012 mg/d) with a
      biodegradable carrier binder, and Ovx trained with endurance exercise. Endurance
      exercise training consisted of continuous running on a motor-driven rodent
      treadmill 5 times per week for 5 weeks. Fat accumulation in liver as well as in
      adipose fat depots was higher (P < .01) in Ovx than in Sham rats. This response
      was prevented in Ovx animals with 17beta-estradiol supplementation and with
      endurance exercise training. Liver gene expressions of sterol regulatory element
      binding protein 1-c, stearoyl coenzyme A desaturase 1 (and its protein content),
      carbohydrate response element binding protein, and acetyl-coenzyme A carboxylase
      were increased with estrogen withdrawal (P < .01). These responses were corrected
      with E2 supplementation alone as well as with training alone. Conversely, hepatic
      peroxisome proliferator-activated receptor alpha messenger RNA levels were lower
      (P < .01) after estrogen removal compared with Sham rats. The lower hepatic
      peroxisome proliferator-activated receptor alpha messenger RNA levels in Ovx rats
      were reincreased by E2 replacement or by exercise training. Gene expression of
      proinflammatory cytokines including inhibitor-kappaB kinase beta and interleukin
      6, as well as protein content of nuclear factor-kappaB, was higher (P < .01) in
      Ovx than in Sham animals. E2 supplementation or exercise training prevented the
      expression of the proinflammatory markers. It is concluded that exercise training
      reduces fat accumulation in liver of Ovx rats possibly through regulation of key
      molecules involved in lipogenesis and lipid oxidation. Exercise training also
      acts as estrogens in properly regulating the expression of inflammatory
      biomarkers in liver of Ovx rats.

PMID- 20674949
TI  - [Training in vascular and interventional radiology. An obstacle race?].

PMID- 20674950
TI  - Progression and survival results after radical hepatic metastasectomy of indolent
      advanced neuroendocrine neoplasms (NENs) supports an aggressive surgical
      approach.
AB  - BACKGROUND: Neuroendocrine neoplasms most commonly metastasize to the liver.
      Operative extirpation of neuroendocrine neoplasm hepatic metastases improves
      symptoms and seems to improve survival, but subsequent evidence is required. The
      current study evaluates the progression-free survival and overall survival of
      patients after resection (with or without ablation) of neuroendocrine neoplasm
      hepatic metastases. As a secondary endpoint, the prognostic factors associated
      with progression-free survival and overall survival were evaluated. METHODS:
      Seventy-four patients with neuroendocrine neoplasm hepatic metastases underwent
      hepatic resection between December 1992 and December 2009. Thirty-eight patients
      underwent synchronous cryoablation. Patients were assessed radiologically and
      serologically at monthly intervals for the first 3 months and then at 6-month
      intervals after treatment. Progression-free survival and overall survival were
      determined; clinicopathologic and treatment-related factors associated with
      progression-free survival and overall survival were evaluated through univariate
      and multivariate analyses. RESULTS: No patient was lost to follow-up. The median
      follow-up for the patients who were alive was 41 months (range, 1-162). The
      median progression-free survival and overall survival after hepatic resection
      were 23 and 95 months, respectively. Five- and 10-year overall survival were 63%
      and 40%, respectively. Two independent factors were associated with overall
      survival: histologic grade (P < .001) and extrahepatic disease (P = .021). The
      only independent predictor for progression-free survival was pathologic margin
      status (P = .023). CONCLUSION: In selected patients, aggressive operative
      extirpation of neuroendocrine neoplasm hepatic metastases is effective in
      achieving long-term survival. Disease progression, however, is a common
      occurrence; therefore, a multimodality treatment approach for progressive disease
      is necessary. Integrating the knowledge of identified prognostic factors can both
      improve patient selection and identify patients at greatest risk of treatment
      failure.

PMID- 20674952
TI  - Tetraodon nigroviridis as a nonlethal model of infectious spleen and kidney
      necrosis virus (ISKNV) infection.
AB  - Infectious spleen and kidney necrosis virus (ISKNV) is the type species of the
      genus Megalocytivirus, family Iridoviridae. We have previously established a high
      mortality ISKNV infection model of zebrafish (Danio rerio). In this study, a
      nonlethal Tetraodon nigroviridis model of ISKNV infection was established. ISKNV
      infection did not cause lethal disease in Tetraodon but could infect almost all
      the organs of this species. Electron microscopy showed ISKNV particles were
      present in infected tissues. Immunofluorescence and quantitative real-time PCR
      analysis showed that nearly all the virions and infected cells were cleared at 14
      d postinfection. The expression profiles of interferon-gamma and tumor necrosis
      factor-alpha gene in response to ISKNV infection were significantly different in
      Tetraodon and zebrafish. The establishment of the nonlethal Tetraodon model of
      ISKNV infection can offer a valuable tool complementary to the zebrafish
      infection model for studying megalocytivirus disease, fish immune systems, and
      viral tropism.

PMID- 20674951
TI  - Characterization of entry and infection of monocytic THP-1 cells by Kaposi's
      sarcoma associated herpesvirus (KSHV): role of heparan sulfate, DC-SIGN,
      integrins and signaling.
AB  - KSHV effectively binds, enters and establishes infection in THP-1 cells with
      initial concurrent expression of latent ORF73 and lytic ORF50 genes and
      subsequent persistence of ORF73. KSHV genome persisted for 30 days and lytic
      cycle could be activated. KSHV utilized heparan sulfate for binding to THP-1
      cells and primary monocytes. Blocking DC-SIGN did not inhibit KSHV binding;
      however, virus entry in THP-1 cells and in primary monocytes was reduced. In
      addition to the previously identified integrins alpha3beta1, alphavbeta3 and
      alphavbeta5, integrin alpha5beta1 was also utilized for infection. KSHV entered
      THP-1 cells via clathrin and caveolin mediated endocytosis and did not utilize
      macropinocytosis as in human dermal endothelial cells, and required an endosomal
      acidification. Infection also induced phosphorylation of FAK, Src, PI3K, NF
      kappaB and ERK1/2 signaling molecules, and entry was blocked by tyrosine kinase
      inhibitors. These findings suggest that THP-1 cells are highly useful model for
      studying KSHV infection of monocytes.

PMID- 20674953
TI  - Genome characterization of a debilitation-associated mitovirus infecting the
      phytopathogenic fungus Botrytis cinerea.
AB  - The full-length sequences of Botrytiscinereamitovirus 1 (BcMV1) and an associated
      RNA (BcMV1-S) in strain CanBc-1c-78 of Botrytis cinerea were determined. Sequence
      analysis showed that BcMV1 is 2804 nt long and AU-rich (66.8%). BcMV1 shares 95%
      nucleotide sequence identity with Ophiostomanovo-ulmimitovirus 3b (OnuMV3b).
      However, it is 472 nt longer than OnuMV3b. Mitochondrial codon usage revealed
      that BcMV1 contains one open reading frame encoding RdRp, which is 96% identical
      to the RdRp of OnuMV3b. These findings confirm that BcMV1 belongs to the genus
      Mitovirus and is a strain of OnuMV3b. BcMV1-S is 2171 nt long and derived from
      BcMV1 through a single internal in-frame deletion of 633 nt, suggesting that it
      is a defective RNA of BcMV1. BcMV1-S was found to suppress the replication of
      BcMV1 and to be co-transmissible with BcMV1 through hyphal anastomosis. Its
      presence, however, did not alleviate the BcMV1-associated debilitation phenotypes
      of B. cinerea.

PMID- 20674955
TI  - Identification and characterization of prohibitin as a receptor protein mediating
      DENV-2 entry into insect cells.
AB  - Dengue is transmitted primarily by mosquitoes of the Aedes genus. Despite a
      number of studies, no insect dengue virus receptor protein has been clearly
      identified and characterized. Using a number of separation methodologies and
      virus overlay protein binding assays we identified a 35kDa protein that
      segregated with susceptibility to dengue serotype 2 (DENV-2) infection in two
      mosquito species and two mosquito cell lines. Mass spectroscopy identified the
      protein to be prohibitin, a strongly conserved and ubiquitously expressed protein
      in eukaryotic cells. Antibody mediated inhibition of infection and siRNA mediated
      knockdown of prohibitin expression significantly reduced infection levels and
      subsequent virus production in both Aedes aegypti and Aedes albopictus cell
      lines. Confocal microscopy showed a significant degree of intracellular
      colocalization between prohibitin and DENV-2 E protein, and coimmunoprecipitation
      confirmed that prohibitin interacts with dengue E. Prohibitin is the first
      characterized insect cell expressed dengue virus receptor protein.

PMID- 20674954
TI  - Significance of host cell kinases in herpes simplex virus type 1 egress and lamin
      associated protein disassembly from the nuclear lamina.
AB  - The nuclear lamina is thought to be a steric barrier to the herpesvirus capsid.
      Disruption of the lamina accompanied by phosphorylation of lamina proteins is a
      conserved feature of herpesvirus infection. In HSV-1-infected cells, protein
      kinase C (PKC) alpha and delta isoforms are recruited to the nuclear membrane and
      PKC delta has been implicated in phosphorylation of emerin and lamin B. We tested
      two critical hypotheses about the mechanism and significance of lamina
      disruption. First, we show that chemical inhibition of all PKC isoforms reduced
      viral growth five-fold and inhibited capsid egress from the nucleus. However,
      specific inhibition of either conventional PKCs or PKC delta does not inhibit
      viral growth. Second, we show hyperphosphorylation of emerin by viral and
      cellular kinases is required for its disassociation from the lamina. These data
      support hypothesis that phosphorylation of lamina components mediates lamina
      disruption during HSV nuclear egress.

PMID- 20674956
TI  - Subcellular localization of the MNV-1 ORF1 proteins and their potential roles in
      the formation of the MNV-1 replication complex.
AB  - Human noroviruses are the leading cause of nonbacterial gastroenteritis worldwide
      and are now recognised as a significant human pathogen. Whereas human noroviruses
      cannot be cultivated in the laboratory, mouse norovirus 1 (MNV-1) is easily
      cultivated and has a defined tropism for cells of a mononuclear origin. As such,
      MNV-1 provides an ideal opportunity to study many aspects of norovirus biology
      and replication. Previously, we have shown that MNV-1 RNA replication is
      associated with components of the early and late secretory pathway and that all
      six open reading frame 1 (ORF1) proteins are associated with the viral dsRNA
      within the replication complex (RC) during the course of infection. In this
      study, we further characterise the subcellular localisation of the MNV-1 ORF1
      proteins when recombinantly expressed in cells. We show that two MNV-1 proteins,
      NS1-2 and NS4, associate with the endoplasmic reticulum and endosomes,
      respectively. Whereas NS6 (the viral protease) appeared to localize within the
      cytoplasm and to mitochondria, NS7 (the viral polymerase) was observed to
      localize diffusely within the cytoplasm and within the nucleus, and NS3 localized
      to discrete foci within the cytoplasm which were of unknown origin. Based on the
      localization patterns observed we propose a model by which NS1-2 and NS4 may
      recruit host membranes to the MNV-1 RC during replication.

PMID- 20674957
TI  - Bacteria permeabilization and disruption caused by sludge reduction technologies
      evaluated by flow cytometry.
AB  - Technologies proposed in the last decades for the reduction of the sludge
      production in wastewater treatment plants and based on the mechanism of cell
      lysis-cryptic growth (physical, mechanical, thermal, chemical, oxidative
      treatments) have been widely investigated at lab-, pilot- and, in some cases, at
      full-scale but the effects on cellular lysis have not always been demonstrated in
      depth. The research presented in this paper aims to investigate how these sludge
      reduction technologies affect the integrity and permeabilization of bacterial
      cells in sludge using flow cytometry (FCM), which permits the rapid and
      statistically accurate quantification of intact, permeabilised or disrupted
      bacteria in the sludge using a double fluorescent DNA-staining instead of using
      conventional methods like plate counts and microscope. Physical/mechanical
      treatments (ultrasonication and high pressure homogenisation) caused moderate
      effects on cell integrity and caused significant cell disruption only at high
      specific energy levels. Conversely, thermal treatment caused significant damage
      of bacterial membranes even at moderate temperatures (45-55  degrees C).
      Ozonation significantly affected cell integrity, even at low ozone dosages, below
      10 mgO(3)/gTSS, causing an increase of permeabilised and disrupted cells. At
      higher ozone dosages the compounds solubilised after cell lysis act as scavengers
      in the competition between soluble compounds and (particulate) bacterial cells.
      An original aspect of this paper, not yet reported in the literature, is the
      comparison of the effects of these sludge reduction technologies on bacterial
      cell integrity and permeabilization by converting pressure, temperature and ozone
      dosage to an equivalent value of specific energy. Among these technologies,
      comparison of the applied specific energy demonstrates that achieving the
      complete disruption of bacterial cells is not always economically advantageous
      because excessive energy levels may be required.

PMID- 20674958
TI  - Munition constituents: Preliminary sediment screening criteria for the protection
      of marine benthic invertebrates.
AB  - Sediment screening criteria for many munition constituents (MC) are not available
      in sources typically used in regulatory-driven ecological risk assessments for
      contaminated sediment sites. Preliminary sediment quality benchmarks (SQBs) for
      MC were developed for screening potential risks to marine benthic invertebrates
      at a munitions contaminated sediment site in Puget Sound, WA, USA. SQBs were
      developed for 2,4,6-trinitrotoluene (TNT) and 13 breakdown products; six other
      explosive nitroaromatic compounds and nitramines (e.g., RDX, HMX); and five
      propellants, plasticizers, and stabilizers. The SQBs were developed using
      freshwater and limited marine aquatic toxicity values (and hence are considered
      preliminary) and equilibrium partitioning theory to relate water concentrations
      of the compounds to sediment concentrations. The SQBs are derived from the lowest
      available aquatic toxicity values for aquatic invertebrates from published
      reviews, original studies, and database sources; ranges of logK(ow) and K(oc)
      values from published reviews and database sources, and some K(oc) values
      calculated from logK(ow). SQBs are presented for 25 MC as organic carbon
      normalized values and as ranges of dry weight values for various levels of
      organic carbon content of sediments. Comparison of the preliminary SQBs with
      method detection limits and sample detection limits achieved at the contaminated
      sediment site demonstrates their utility in risk screening of benthic
      invertebrates.

PMID- 20674959
TI  - Climate driven release of carbon and mercury from permafrost mires increases
      mercury loading to sub-arctic lakes.
AB  - In sub-arctic and arctic regions mercury is an element of concern for both
      wildlife and humans. Over thousands of years large amounts of atmospherically
      deposited mercury, both from natural and anthropogenic sources, have been
      sequestered together with carbon in northern peatlands. Many of these peatlands
      are currently underlain by permafrost, which controls mire stability and
      hydrology. With the ongoing climate change there is concern that permafrost
      thawing will turn large areas of these northern peatlands from carbon/mercury
      sinks into much wetter carbon/mercury-sources. Here we can show that such a
      change in mire structure in the sub-arctic Stordalen mire in northern Sweden
      actually is responsible for an increased export of mercury to the adjacent lake
      Inre Harrsjon. We also show that sediment mercury accumulation rates during a
      warm period in the pre-industrial past were higher than in the 1970s when
      atmospheric input peaked, indicating that in areas with permafrost, climate can
      have an effect on mercury loading to lakes as large as anthropogenic emissions.
      Thawing of permafrost and the subsequent export of carbon is a widespread
      phenomenon, and the projection is that it will increase even more in the near
      future. Together with our observations from Stordalen, this makes northern
      peatlands into a substantial source of mercury, at risk of being released into
      sensitive arctic freshwater and marine systems.

PMID- 20674960
TI  - Induction of metachromasia in cationic dyes and fluorochromes using a clay
      mineral: a potentially valuable model for histochemical studies.
AB  - The use of simple model substrates to analyze conditions and mechanisms of
      metachromatic reactions is an important strategy in histochemical studies. In
      this study we show that in the presence of the three-layered silicate clay
      montmorillonite, diluted solutions of thionine and toluidine blue develop an
      immediate metachromatic shift (from blue to reddish violet). Likewise,
      hypoemission and red shift in the fluorescence spectra of acridine orange,
      pyronine Y and ethidium bromide appear when montmorillonite is added to the dye
      solution. Cationic dyes could insert as stacked structures into the negatively
      charged interlamellar spaces of the clay. These spectral results indicate that on
      account of its strong aggregating capacity, montmorillonite is a suitable model
      substrate to study metachromatic reactions.

PMID- 20674961
TI  - Serum leptin-adiponectin ratio and endometrial cancer risk in postmenopausal
      female subjects.
AB  - OBJECTIVE: Obesity is a well-known risk factor for the development of endometrial
      cancer. Elevated endogenous estrogen and insulin resistance are recognized to be
      major factors that link obesity and cancer development. However, there is
      increasing evidence that the adipokines adiponectin and leptin, which are
      directly produced in adipose tissue, impact several obesity-related cancers. The
      purpose of the current study was to investigate the relationships of the
      concentration of leptin, adiponectin, and the leptin-to-adiponectin ratio (L/A
      ratio) with the endometrial cancer risk in postmenopausal female subjects.
      METHODS: A case-control study was performed in 146 postmenopausal female subjects
      with endometrial cancer and 150 control subjects with no history of cancer. The
      serum levels of the adipokines leptin and adiponectin were measured, and the
      associations of these adipokines and the L/A ratios with the endometrial cancer
      risk were analyzed. RESULTS: The leptin levels and the L/A ratios were
      significantly higher in the incident cases of endometrial cancer (8.2 +/- 0.5,
      2.05 +/- 1.08 ng/ml) than in the controls subjects (4.5 +/- 0.5, 0.98 +/- 0.18,
      P<0.0001), whereas the adiponectin levels were significantly lower in the
      incident cases (6.2 +/- 0.4 MUg/ml) than in the control subjects (9.0 +/- 0.4
      MUg/ml, P<0.0001). For the incident cases, the serum levels of the adipokines
      were significantly correlated with the patient body mass index (BMI) (P<0.001 for
      leptin, P<0.05 for adiponectin), and the leptin levels and the L/A ratios were
      significantly correlated with the homeostasis model assessment ratio (HOMA-R) and
      the fasting insulin levels (P<.001). Higher L/A ratios were found to be
      significantly associated with an increased risk of endometrial cancer [OR (95%
      CI) for the top vs. the bottom tertile of the L/A ratio was 6.0 (3.2-11.9), P
      value<0.0001]. Moreover, the ORs of the L/A ratios were higher than those of
      leptin or adiponectin alone. The association of the L/A ratios with endometrial
      cancer risk remained after adjusting for the obesity indices, hypertension, and
      presence of diabetes mellitus. CONCLUSION: The present results suggested that the
      L/A ratio was independently associated with an increased risk for endometrial
      cancer development. Additional research will elucidate the molecular mechanisms
      by which these adipokines are associated with the development of endometrial
      cancer.

PMID- 20674962
TI  - Epothilone B enhances surface EpCAM expression in ovarian cancer Hey cells.
AB  - OBJECTIVES: Epothilone B (EpoB), like Taxol, stabilizes microtubules resulting in
      an inhibition of microtubule dynamic instability. The drug is being evaluated in
      phase III clinical trials. An EpoB analog, Ixabepilone, was approved by the FDA
      for the treatment of taxane-resistant metastatic breast cancer. Epithelial cell
      adhesion antigen (EpCAM) expression is significantly higher in epithelial ovarian
      cancer cells compared to normal cells. The effects of EpoB and other microtubule
      interacting agents on surface EpCAM expression were studied. METHODS: Biochemical
      methods, immunofluorescence and flow cytometry were used to identify EpCAM
      expression on the surface of the ovarian cancer cell line, Hey, after exposure to
      EpoB. The relationship between EpoB-mediated surface EpCAM expression and EpoB
      induced alpha-tubulin acetylation, a surrogate marker for stable microtubules, in
      Hey cells also was investigated. RESULTS: Nanomolar concentrations of EpoB,
      Taxol, discodermolide or vinblastine caused a marked increase in surface EpCAM
      expression in Hey cells. Alpha-tubulin acetylation was increased following
      treatment with Taxol, EpoB and discodermolide, but not with vinblastine,
      indicating that drug-enhanced surface EpCAM expression does not correlate with
      tubulin acetylation or stabilization. Unexpectedly, EpoB did not have a
      significant effect on EpCAM mRNA expression, nor did it alter the level of total
      cellular EpCAM in Hey cells. CONCLUSIONS: The results indicate that disruption of
      the microtubule cytoskeleton is associated with the redistribution of cell
      surface antigens in ovarian cancer cells. The increase in cell surface EpCAM
      antigen density may facilitate the antibody targeting of EpCAM-positive ovarian
      cancer cells.

PMID- 20674963
TI  - Exposure of rye (Secale cereale) cultivars to elevated ozone levels increases the
      allergen content in pollen.

PMID- 20674964
TI  - Efficacy of sublingual immunotherapy with grass allergens for seasonal allergic
      rhinitis: a systematic review and meta-analysis.
AB  - BACKGROUND: The benefit of sublingual immunotherapy (SLIT) with grass allergens
      for seasonal allergic rhinitis has been extensively studied, but data on efficacy
      are still equivocal. OBJECTIVE: To assess the effectiveness of SLIT with grass
      allergens in the reduction of symptoms and medication in patients with seasonal
      allergic rhinitis to grass pollen. METHODS: Computerized bibliographic searches
      of MEDLINE (1995-2010) were supplemented by hand searches of reference lists.
      Studies were included if they were double-blind randomized controlled trials
      (RCTs) comparing SLIT to placebo and if they included patients with history of
      allergy to grass pollen treated with natural grass pollen extracts. Nineteen RCTs
      with 2971 patients were analyzed. The outcomes assessed were symptom and
      medication scores. RESULTS: Using a random-effects model, SLIT with grass
      allergens significantly reduces both symptoms (standardized mean difference, 
      0.32; 95% CI, -0.44 to -0.21) and medication use (standardized mean difference, 
      0.33; 95% CI, -0.50 to -0.16) compared with placebo. The treatment is more
      efficacious in adults than in children. Prolonging duration of preseasonal
      treatment for more than 12 weeks improves the treatment efficacy. CONCLUSION:
      This meta-analysis found that SLIT with grass allergens is effective in patients
      with seasonal allergic rhinitis compared with placebo. The benefit is clinically
      modest, and criteria are needed to identify patients most likely to benefit from
      SLIT.

PMID- 20674965
TI  - Patients' safety for global health.

PMID- 20674966
TI  - The case for a global rare-diseases registry.

PMID- 20674967
TI  - A highly elastic tissue sealant based on photopolymerised gelatin.
AB  - Gelatin is widely used as a medical biomaterial because it is readily available,
      cheap, biodegradable and demonstrates favourable biocompatibility. Many
      applications require stabilisation of the biomaterial by chemical crosslinking,
      and this often involves derivatisation of the protein or treatment with cytotoxic
      crosslinking agents. We have previously shown that a facile photochemical method,
      using blue light, a ruthenium catalyst and a persulphate oxidant, produces
      covalent di-tyrosine crosslinks in resilin and fibrinogen to form stable hydrogel
      biomaterials. Here we show that various gelatins can also be rapidly crosslinked
      to form highly elastic (extension to break >650%) and adhesive (stress at break
      >100 kPa) biomaterials. Although the method does not require derivatisation of
      the protein, we show that when the phenolic (tyrosine-like) content of gelatin is
      increased, the crosslinked material becomes resistant to swelling, yet retains
      considerable elasticity and high adhesive strength. The reagents are not
      cytotoxic at the concentration used in the photopolymerisation reaction. When
      tested in vivo in sheep lung, the photopolymerised gelatin effectively sealed a
      wound in lung tissue from blood and air leakage, was not cytotoxic and did not
      produce an inflammatory response. The elastic properties, thermal stability,
      speed of curing and high tissue adhesive strength of this photopolymerised
      gelatin, offer considerable improvement over current surgical tissue sealants.

PMID- 20674968
TI  - Effects of pseudowollastonite (CaSiO3) bioceramic on in vitro activity of human
      mesenchymal stem cells.
AB  - We report the effects of two pseudowollastonite (beta-CaSiO(3)) substrates on the
      attachment, viability, proliferation and osteogenic differentiation of human
      mesenchymal stem cells (hMSCs), and provide detailed mechanistic links of surface
      texture, soluble factors and culture media to cell activities. Cell attachment
      and viability were lower for psWf (fine-grained, roughness 0.74 microm) than for
      psWc (coarse-grained, roughness 1.25 microm) surface, and were ascribed to the
      greater specific area of the finer psWf particles resulting in higher release
      rate of Si, which is cytotoxic at high levels. Interestingly, proliferation was
      greater on psWf. Osteogenic differentiation occurred on both surfaces, indicated
      by calcium phosphate bone nodule formation and by osteocalcin, osteopontin and
      core-binding factor alpha-1 gene expression. Gene levels were lower on psWf than
      on psWc at day 8 in growth medium, explained by differences in Ca and/or Si
      concentrations between the two surfaces. Similar gene expression on both surfaces
      at day 16 in both growth and osteogenic induction media was attributed to pro
      osteogenic effects of Ca and P at specific concentrations and complementary Ca
      and P levels on the two surfaces. In summary, soluble factors from substrates may
      be more important for osteogenic differentiation in growth medium than small
      surface roughness variations within a factor of 2. Optimum concentration ranges
      exist for individual soluble factors to balance cell toxicity/growth versus
      osteogenic differentiation, and soluble factors together have complex,
      cooperative or opposing, effects on a given cell activity.

PMID- 20674969
TI  - Biomaterials derived from silk-tropoelastin protein systems.
AB  - A structural protein blend system based on silkworm silk fibroin and recombinant
      human tropoelastin is described. Silk fibroin, a semicrystalline fibrous protein
      with beta-sheet crystals provides mechanical strength and controllable
      biodegradation, while tropoelastin, a noncrystallizable elastic protein provides
      elasticity. Differential scanning calorimetry (DSC) and temperature modulated DSC
      (TMDSC) indicated that silk becomes miscible with tropoelastin at different blend
      ratios, without macrophase separation. Fourier transform infrared spectroscopy
      (FTIR) revealed secondary structural changes of the blend system (beta-sheet
      content) before and after methanol treatment. Atomic Force Microscopy (AFM) nano
      indentation demonstrated that blending silk and tropoelastin at different ratios
      resulted in modification of mechanical features, with resilience from
      approximately 68%- approximately 97%, and elastic modulus between 2 and 9 Mpa,
      depending on the ratio of the two polymers. Some of these values are close to
      those of native aortic elastin or elastin-like polypeptides. Significantly,
      during blending and drying silk-tropoelastin form micro- and nano-scale porous
      morphologies which promote human mesenchymal stem cell attachment and
      proliferation. These blends offer a new protein biomaterial system for cell
      support and tailored biomaterial properties to match mechanical needs.

PMID- 20674970
TI  - FGF-2 and VEGF functionalization of starPEG-heparin hydrogels to modulate
      biomolecular and physical cues of angiogenesis.
AB  - Tissue engineering therapies require biomaterials capable of encouraging an
      angiogenic response. To dissect the influence of different pro-angiogenic stimuli
      a set of starPEG-heparin hydrogels with varied physicochemical properties was
      used as a highly efficient reservoir and tunable delivery system for basic
      fibroblast growth factor (FGF-2) and vascular endothelial growth factor (VEGF).
      The engineered gel materials could be precisely tailored by decoupling the
      biomolecular functionalization from the variation of the viscoelastic matrix
      characteristics. Culture experiments with human umbilical vein endothelial cells
      (HUVECs) revealed the interplay of growth factor presentation, adhesive
      characteristics and elasticity of the gel matrices in triggering differential
      cellular behavior which allowed identifying effective pro-angiogenic conditions.

PMID- 20674971
TI  - Long term culture of human embryonic stem cells on recombinant vitronectin in
      ascorbate free media.
AB  - Human embryonic stem cells (hESC) are expected to provide revolutionary
      therapeutic applications and drug discovery technologies. In order for this to be
      achieved a reproducible, defined animal component free culture system is required
      for the scale-up production of undifferentiated hESC. In this work we have
      investigated the applicability of a recombinantly produced domain of human
      vitronectin as an extracellular matrix alternative to the common standards
      Geltrex or Matrigel. In addition we have validated an ascorbate free media
      capable of supporting CD30(low) populations of hESC through a multi-factorial
      analysis of bFGF and Activin A. The recombinant vitronectin domain combined with
      the ascorbate free media were capable of supporting 3 cell lines, MEL1, MEL2 and
      hES3 for 10 or more passages while maintaining hESC pluripotency markers and
      differentiation capacity. The culture method outlined here provides a platform
      for future investigation into growth factor and extracellular matrix effects on
      hESC maintenance prior to bioreactor scale-up.

PMID- 20674972
TI  - Expression of regulatory T cell (Treg) activation markers in endometrial tissues
      from early and late pregnancy in the feline immunodeficiency virus (FIV)-infected
      cat.
AB  - Regulatory T cells (Tregs) support pregnancy maintenance by suppressing placental
      inflammation, while diminished Treg function may accompany reproductive failure.
      Experimental FIV infection frequently results in vertical transmission and
      increased pregnancy failure in the cat. The mechanism of reproductive compromise
      is unknown. We hypothesized that FIV infection alters endometrial Treg population
      dynamics and function, potentiating vertical transmission and reproductive
      failure. RNA collected from early and late gestation reproductive tissue and
      fetuses from FIV infected and control cats was probed for expression of FIV gag
      and Treg markers CD25, FOXP3, and CTLA4, using real time reverse-transcriptase
      (RT)-PCR. Frequent placental and fetal infection and reproductive failure were
      detected at early and late pregnancy. Expression of FOXP3 and CTLA4 was higher in
      early gestation tissues from control cats. FIV infection significantly reduced
      expression of FOXP3 and CTLA4 at early, but not late pregnancy. At late
      pregnancy, CTLA4 was expressed to higher levels in infected tissues. The number
      of tissues with decreased co-expression of FOXP3 and CTLA4 was significant in
      infected cats at early pregnancy. No significant changes in CD25 expression
      occurred between FIV-infected and control animals at early or late pregnancy.
      Differences in Treg marker expression were not significant between viable and non
      viable pregnancies in infected cats. The detection of Treg markers in these
      feline tissues provides the first evidence of feline endometrial Tregs and
      suggests that such cells diminish as pregnancy progresses. These cells may be
      depleted or rendered less functional by viral infection, but understanding their
      role in pregnancy requires further study.

PMID- 20674973
TI  - Quantification of CD20 mRNA and protein levels in chronic lymphocytic leukemia
      suggests a post-transcriptional defect.
AB  - Chronic lymphocytic leukemia is less effectively treated than other B cell
      malignancies with the anti-CD20 agent, rituximab, presumably due, at least in
      part, to low CD20 expression. CD20 expression is typically measured by flow
      cytometry, which may not be quantitative. This study was undertaken to measure
      total CD20 protein in CLL B cells using quantitative immunoblot analysis. The
      results demonstrated that total CD20 protein levels were consistently decreased
      by ~60% in CLL B cells with low CD20 fluorescence staining. Surprisingly, real
      time polymerase chain reaction analysis showed that CD20 mRNA levels were normal
      or close to normal, depending on the comparative B cell population, and did not
      correlate well with protein expression. We conclude that CD20 protein is
      substantially decreased in CLL due to a post-transcriptional defect.

PMID- 20674974
TI  - Clonal selection of 11q CN-LOH and CBL gene mutation in a serially studied
      patient during MDS progression to AML.
AB  - By conventional metaphase and SNP array cytogenetics we serially studied a
      patient affected by high-risk myelodysplastic syndrome (MDS), documenting the
      conversion from partial trisomy 8q to trisomy 8 and partial tetrasomy 8q during
      progression to acute myeloid leukemia (AML). Moreover, the serial application of
      high resolution genomic array analysis at different disease stages allowed the
      description of cryptic abnormalities and the demonstration of their enrichment in
      the AML phase. In particular the detection and quantification of a copy-neutral
      loss of heterozygosity region located in chromosome 11q guided the search for
      point mutations in the CBL gene, thus allowing the escription of the novel
      missense mutation K382E and the demonstration of its selection during progression
      to secondary AML.

PMID- 20674975
TI  - Predicting the unpredictable? Identifying high-risk versus low-risk parents with
      intellectual disabilities.
AB  - OBJECTIVES: This study set out to identify risk factors affecting parents with
      intellectual disabilities (IDs) by determining: (i) whether perception of family
      support differs between parents with IDs, referring professionals, and a
      specialist parenting service; (ii) whether multivariate familial and demographic
      factors differentiates 'high-risk' from 'low-risk' parenting; and (iii) the
      impact of partner relationships on parental competency and risk status. METHODS:
      Secondary data analysis was conducted on data gathered from 101 parents with IDs
      and 172 of their children, all of whom had been referred to a specialist
      parenting service over a 5 year period. RESULTS: Cross-tabulations were applied
      to the data to examine causal processes and to improve general understanding of
      the risks associated with families. Contrary to popular expectations IQ levels of
      the main parent, relationship status, parental age, employment, amenities, valued
      support and parents' perception of need were not identified as contributory
      factors distinguishing 'high-risk' from 'low-risk' parents. Instead, 'high-risk'
      parenting associated more with parental reports of childhood trauma (emotional
      abuse and physical neglect in particular), parents' having additional special
      needs in addition to their IDs or parents who were raising a child with special
      needs. Other 'high-risk' factors identified related to the male partners of
      mothers with IDs, many of whom did not have IDs and/or whose histories included
      anti-social behaviors or criminality. CONCLUSIONS: The study identified some high
      risk variables among parents with IDs that can distinguish them from low-risk
      parents with IDs. PRACTICE IMPLICATIONS: These findings generate challenges for
      agencies who attempt to capture the needs of parents with IDs and who endeavour
      to provide services to families deemed to be "at risk." These outcomes will be of
      special interest to the courts, especially when parents with IDs are involved in
      care proceedings.

PMID- 20674976
TI  - Effects of urban particulate deposition on microbial communities living in
      bryophytes: an experimental study.
AB  - Our previous in situ study showed that bryophyte-microorganism complexes were
      affected by particulate atmospheric pollution. Here, the effect of urban
      particulate wet deposits on microbial communities living in bryophytes was
      studied under controlled conditions. An urban particulate solution was prepared
      with particles extracted from analyzer' filters and nebulized on bryophytes in
      treatments differing in frequency and quantity. The bryophytes did not accumulate
      metallic trace elements, which were present in very weak concentrations. However,
      in treated microcosms the total microbial biomass and the biomasses of
      cyanobacteria, active testate amoebae and fungi significantly decreased in
      response to the deposition of particles. These results confirm that microbial
      communities living in terrestrial bryophytes could be more sensitive indicators
      of atmospheric pollution than bryophytes. Moreover, they suggest that unicellular
      predators--such as testate amoebae--could be especially useful microbial
      indicators, since they seem to be both directly and indirectly affected by
      pollution.

PMID- 20674977
TI  - Anti-oxidative status and hepatic enzymes following acute administration of
      diethyl phthalate in olive flounder Paralichthys olivaceus, a marine culture
      fish.
AB  - Although diethyl phthalate (DEP) is one of the most frequently used phthalates in
      solvents and fixatives for numerous industrial products, almost no research has
      been done on its biochemical toxicity in aquatic animals. Olive flounder
      (Paralichthys olivaceus), an important culture fish in far eastern Asian
      countries, were treated with intraperitoneal DEP at 0, 100, 300 or 900 mg/kg for
      three consecutive days and biochemical effects were assessed in the liver, kidney
      and serum 24 h after the final dosing. Measured parameters were mostly restricted
      to oxidative status and toxicity of the organs. In the hepatic tissue, there were
      significant increases in lipid peroxide (LPO) at 100mg/kg and above. Other
      hepatic parameters, which were examined, changed only after 900 mg/kg: reduced
      glutathione content (GSH), glutathione reductase activity (GR), glutathione
      peroxidase (GPx) activity increased; catalase (CAT) activity decreased. DEP also
      induced elevation in LPO levels at above 100 mg/kg in renal tissues; however,
      there was only a decrease in GR and glutathione S-transferase (GST) activities
      with DEP 900 mg/kg in contrast to the liver. Enzyme activities of aspartate
      aminotransferase (AST) and alanine aminotransferase (ALT) in hepatic tissues
      decreased in a dose-dependent manner in response to DEP at above 300 mg/kg. DEP
      at 300-900 mg/kg, although not uniform among parameters, caused increases in
      serum alkaline phosphatase (ALP), lactate dehydrogenase (LDH), AST, ALT
      activities and osmolality value, suggesting that DEP at these doses induced
      hepatic cell damage. The results indicate that 100-900 mg/kg DEP induced
      oxidative stress and the fish seemed to activate compensatory anti-oxidant
      systems to cope with the imposed substance on the liver. Such compensatory
      activation was not evident in the kidney. Overall, DEP was only weakly toxic to
      olive flounder in terms of oxidative and hepatic damage.

PMID- 20674978
TI  - Social network and health outcomes among African American cardiac rehabilitation
      patients.
AB  - OBJECTIVE: We tested the hypotheses that the number of close social network
      members and the health-related support provided by social network members are
      predictive of coping efficacy and health behaviors. METHODS: Cross-sectional data
      were collected from 115 African Americans enrolled in cardiac rehabilitation.
      Measures included the social convoy model, SF-36, the Social Interaction
      Questionnaire, the Patient Self-Efficacy Questionnaire, and an investigator
      developed assessment of health behaviors. RESULTS: Bivariate relationships were
      found between the number of inner network members and coping efficacy (r = .19, P
      < .05) and health behaviors (r = .18, P < .06), and between health-related
      support and coping efficacy (r = .22, P < .05) and health behaviors (r = .28, P <
      .001). Regression analyses support the hypothesis that close network members
      predicted better coping efficacy (beta = .18, P < .05) and health behaviors (beta
      = .19, P < .05). Health-related support also predicted coping efficacy (beta =
      .23, P < .05) and health behaviors (beta = .30, P < .01). CONCLUSION: African
      Americans with larger inner networks have more health support, better health
      behaviors, and higher coping efficacy. The number of close social network members
      and related health-support promote health through health behaviors and coping
      efficacy.

PMID- 20674979
TI  - Multiple mycotic aneurysms reveal Staphylococcus lugdunensis endocarditis in a
      young patient.
AB  - Mycotic aneurysms are rare, and depending on their location, can threaten
      functional prognosis. We report on a 17-year-old girl with no previous history of
      cardiovascular or infectious disease, referred to our Department of Cardiology
      with right hemiplegia and aphasia. A neurological evaluation revealed thrombosis
      of a mycotic cerebral aneurysm, complicated by ischemic and hemorrhagic
      infarction. Transthoracic echocardiography indicated huge, highly mobile mitral
      vegetation associated with a mitral regurgitation with a triple stream.
      Hemocultures isolated Staphylococcus lugdunensis. Shortly afterward, she
      developed bilateral tibial and pedal mycotic aneurysm. The patient received
      antibiotics, with minor neurological improvement initially, but she soon died
      because of a brain herniation. Based on our findings in this case, we discuss the
      features of endocarditis attributable to S. lugdunensis.

PMID- 20674980
TI  - Working with evaluation stakeholders: A rationale, step-wise approach and
      toolkit.
AB  - In the broad field of evaluation, the importance of stakeholders is often
      acknowledged and different categories of stakeholders are identified. Far less
      frequent is careful attention to analysis of stakeholders' interests, needs,
      concerns, power, priorities, and perspectives and subsequent application of that
      knowledge to the design of evaluations. This article is meant to help readers
      understand and apply stakeholder identification and analysis techniques in the
      design of credible evaluations that enhance primary intended use by primary
      intended users. While presented using a utilization-focused-evaluation (UFE)
      lens, the techniques are not UFE-dependent. The article presents a range of the
      most relevant techniques to identify and analyze evaluation stakeholders. The
      techniques are arranged according to their ability to inform the process of
      developing and implementing an evaluation design and of making use of the
      evaluation's findings.

PMID- 20674981
TI  - Low temperature photo-oxidation of chloroperoxidase Compound II.
AB  - Oxidation of the heme-thiolate enzyme chloroperoxidase (CPO) from Caldariomyces
      fumago with peroxynitrite (PN) gave the Compound II intermediate, which was photo
      oxidized with 365 nm light to give a reactive oxidizing species. Cryo-solvents at
      pH ~ 6 were employed, and reactions were conducted at temperatures as low as -50
      degrees  C. The activity of CPO as evaluated by the chlorodimedone assay was
      unaltered by treatment with PN or by production of the oxidizing transient and
      subsequent reaction with styrene. EPR spectra at 77K gave the amount of ferric
      protein at each stage in the reaction sequence. The PN oxidation step gave a 6:1
      mixture of Compound II and ferric CPO, the photolysis step gave an approximate
      1:1 mixture of active oxidant and ferric CPO, and the final mixture after
      reaction with excess styrene contained ferric CPO in 80% yield. In single
      turnover reactions at -50 degrees C, styrene was oxidized to styrene oxide in
      high yield. Kinetic studies of styrene oxidation at -50 degrees C displayed
      saturation kinetics with an equilibrium constant for formation of the complex of
      K(bind)=3.8 x 10(4)M(-1) and an oxidation rate constant of k(ox)=0.30s(-1). UV
      Visible spectra of mixtures formed in the photo-oxidation sequence at ca. -50
      degrees  C did not contain the signature Q-band absorbance at 690 nm ascribed to
      CPO Compound I prepared by chemical oxidation of the enzyme, indicating that
      different species were formed in the chemical oxidation and the photo-oxidation
      sequence.

PMID- 20674982
TI  - Patient predictors of response to cognitive behaviour therapy and interpersonal
      psychotherapy in a randomised clinical trial for depression.
AB  - OBJECTIVES: This study examined patient predictors of response to interpersonal
      psychotherapy (IPT) and cognitive behaviour therapy (CBT). METHOD: Participants
      were 177 adults with a primary diagnosis of major depressive disorder randomised
      to 16 weekly sessions of either IPT or CBT. Pre and post treatment depressive
      symptomatology was assessed by an independent clinician with the Montgomery
      Asberg Depression Rating Scale. RESULTS: General predictors of response were
      perceived logic of therapy, recurrent depression and childhood reasons for
      depression (r2 =.21). Only one differential predictor of treatment response was
      identified. Increasing comorbid personality disorder symptoms was associated with
      decreases in response to IPT but not CBT. CONCLUSION: The results indicate that
      attention to specific pretreatment patient factors may enhance response to
      psychotherapy.

PMID- 20674983
TI  - Brain derived neurotrophic factor gene polymorphism (Val66Met) and short-term
      antidepressant response in major depressive disorder.
AB  - BACKGROUNDS: To determine the association between the brain derived neurotrophic
      factor (BDNF) Val66Met polymorphism and short-term antidepressant response in
      Taiwanese patients with major depressive disorder (MDD). METHODS: We recruited
      117 MDD patients who were randomized to fluoxetine or venlafaxine treatment and
      106 controls. The association between genotypes and percentage changes in the
      Hamilton Rating Scale for Depression (HAM-D) scores over time was analyzed by
      repeated-measures ANOVA. The antidepressants were included in the model as
      covariates. RESULTS: The frequency of the BDNF Val66Met polymorphisms was not
      significantly different between patient and control groups. Significantly changes
      in HAM-D scores were noted after 2 and 4 weeks of venlafaxine treatment among
      different genotypes. CONCLUSIONS: Results suggest antidepressants acting through
      different mechanisms may affect the BDNF Val66Met polymorphism differently.

PMID- 20674984
TI  - Brain-derived neurotrophic factor and serotonin transporter gene-linked promoter
      region genes alter serum levels of brain-derived neurotrophic factor in humans.
AB  - BACKGROUND: Polymorphisms in the brain-derived neurotrophic factor (BDNF)
      val66met and serotonin transporter gene-linked promoter region (5-HTTLPR) are
      associated with alterations in mood and BDNF protein, but the effects of two
      genetic variations on the serum level of BDNF is unclear. Therefore, we sought to
      explore the effects of two polymorphisms on serum levels of BDNF in healthy
      subjects. METHODS: One hundred healthy Korean subjects were genotyped. Serum
      levels of BDNF were measured with enzyme-linked immunoassay, and factors (sex,
      age, body mass index, alcohol and smoking) that can affect BDNF level were
      evaluated. The effects of these two genetic variations on serum levels of BDNF
      were tested using an analysis of covariance. RESULTS: We found that serum levels
      of BDNF were significantly affected by the factor 'genotype' (met carrier vs. val
      homozygote) (F=4.618, p=0.034) and (s homozygote vs. l carrier) (F=3.965,
      p=0.049), respectively. Moreover, subjects with s homozygosity at the 5-HTTLPR
      and BDNF met carriers (16.2+/-7.9 ng/ml) had lower serum levels of BDNF as
      compared with those with l carriers of the 5-HTTLPR in combination with BDNF val
      homozygosity (21.7+/-4.4 g/ml) (p=0.024). LIMITATIONS: A larger study will be
      needed to confirm this additive effect of both risk genotypes. CONCLUSIONS: In
      this study, we report for the first time that healthy subjects who were
      homozygous for s at 5HTTLPR and the met allele of the BDNF val66met polymorphism
      displayed significantly lower serum levels of BDNF. Our findings might contribute
      to a better understanding of the effect of BDNF and 5-HTTLPR gene on serum BDNF
      level in humans.

PMID- 20674985
TI  - Fibromyalgia syndrome and depressive symptoms: comorbidity and clinical
      correlates.
AB  - OBJECTIVE: Fibromyalgia is characterized by chronic widespread musculoskeletal
      pain and higher pain perception in specific anatomic sites called tender points.
      Fibromyalgia is frequently associated with psychiatric symptoms, like depression
      and anxiety; indeed some authors have argued about the possibility to classify
      this syndrome into affective spectrum disorder. Few studies have analyzed the
      impact of depressive symptoms on pain threshold. This research is aimed at
      evaluating the prevalence and the clinical correlates of depressive symptoms in
      fibromyalgic patients, and investigating their impact on pain perception and
      quality of life. METHODS: Outpatients between 18 and 75 years with diagnosis of
      fibromyalgia according to the criteria of the American College of Rheumatology
      have been included. All subjects have been evaluated with the following rating
      scales: HAM-D; VAS (to quantify pain); a visual analogical scale to evaluate
      quality of life; and Paykel's List of Recent Life Events. RESULTS: Thirty
      subjects have been recruited. Most patients (83.3%) had clinically significant
      depressive symptoms as indicated by a HAM-D score >7. Depressive symptoms are
      associated with higher pain perception, worse quality of life and more severe
      life events. CONCLUSION: The presence of depressive symptoms is associated with a
      great impairment in patients with fibromyalgia syndrome: indeed the psychiatric
      comorbidity lowers pain threshold and worsens the quality of life of our
      patients. Future studies should be conducted in order to identify the individual
      factors, e.g. stress or inflammatory processes, which drive the association
      between depression and higher severity of fibromyalgia syndrome.

PMID- 20674986
TI  - Bipolar disorder and polymorphisms of glutathione S-transferases M1 (GSTM1) and
      T1 (GSTT1).
AB  - Glutathione S-transferases are ubiquitous multifunctional enzymes, which play a
      key role in cellular detoxification. The present case-control study was performed
      in Shiraz, Iran to investigate the association between polymorphisms of
      glutathione S-transferases M1 (GSTM1) and T1 (GSTT1) and susceptibility to
      bipolar disorder (BPD). A total of 228 BPD patients participated in the study. In
      addition, 236 healthy blood donors, who frequency matched with the patients
      according to age and gender, were also studied as a control group. Statistical
      analysis revealed that polymorphisms of neither GSTM1 (OR=0.73, 95% CI: 0.50
      1.05) nor GSTT1 (OR=0.98, 95% CI: 0.65-1.47) were associated with risk of BPD.
      Patients were stratified according to their age of onset into early onset (below
      19 years old) and late onset (more than 19 years old) groups. Among the early
      onset group, the GSTM1 null genotype decreases the risk of BPD (OR=0.43, 95% CI:
      0.24-0.79). Further analysis showed that a combination of "GSTM1 positive
      genotype and GSTT1 null genotype" versus "positive genotypes of GSTM1 and GSTT1"
      increased the risk of BPD (OR=2.28, 95% CI: 1.07-4.85). However, there was no
      significant association between the study polymorphisms and risk of BPD among the
      late onset group. The present finding indicated that GSTM1 and GSTT1 are
      candidate polymorphisms for susceptibility to BDP among adolescents.

PMID- 20674987
TI  - Optimization of a procedure to accurately detect equine TNFalpha in serum
      samples.
AB  - The systemic component of chronic inflammatory diseases may lead to clinical
      complications. High levels of TNFalpha, a pro-inflammatory cytokine, are found in
      human patients with COPD and asthma. Horses are also susceptible to an array of
      chronic inflammatory disorders possibly associated with systemic inflammation,
      including respiratory diseases. Currently, there is no commercially available
      ELISA validated to assess TNFalpha in equine serum samples. Moreover, the
      reported normal mean concentration of serum TNFalpha in horses vary greatly.
      Hence, we sought to optimize and validate a procedure to quantify this cytokine
      in equine serum samples using a sandwich ELISA. Our results indicate that the
      nature of diluent buffers greatly impact the detection of TNFalpha in equine
      serum samples as its quantification increased in some cases from non-detectable
      levels to the ng/ml range. Linearity assays performed with serum samples from six
      animals serially diluted in four different buffers showed that serum matrix
      interference was animal-dependant. The specificity of TNFalpha detection was also
      assessed. Our optimized assay conditions were validated by quantifying levels of
      TNFalpha in serum samples from normal horses and horses affected with chronic
      pulmonary disease (heaves).

PMID- 20674988
TI  - Development and characterization of mouse monoclonal antibodies specific for
      chicken interleukin 18.
AB  - Four mouse monoclonal antibodies (mAbs) which are specific for chicken
      interleukin 18 (chIL18) were produced and characterized by enzyme-linked
      immunosorbent assay (ELISA), Western blotting, quantitative real-time PCR and
      neutralization assays. Using Western blot analysis, monoclonal antibodies
      specific for chIL18 identified a 23 kDa Pichia pastoris-expressed chIL18 and 66
      kDa E. coli-derived MBP fusion protein of chIL18. Bioassays for chIL18 using
      primary chicken spleen cells showed dose-dependent IFN-gamma mRNA expression and
      induction of IFN-gamma from primary splenocytes, and triggered nitric oxide (NO)
      production in the HD11 macrophage cell line. These mAbs showed neutralizing
      chIL18 activity. Taken together, these mouse mAbs which detect chicken IL-18 will
      be significant new immune reagents and useful tools for basic and applied
      research in poultry.

PMID- 20674989
TI  - Feline pancreatic islet-like clusters and insulin producing cells express
      functional Toll-like receptors (TLRs).
AB  - Toll-like receptors (TLRs) are cellular receptors that recognize molecules
      derived from pathogens, endogenous molecules generated after cellular stress, and
      free fatty acids. TLR activation leads to a proinflammatory reaction that is
      fundamental in the initiation of an innate immune response and subsequent
      adaptive responses but also can damage tissues. TLRs are not only expressed
      within the immune system, but also in most other organ systems including the
      pancreas. TLR4 is expressed in pancreatic beta-cells of rodents and humans and
      its stimulation affects insulin secretion in response to glucose. A low-grade
      inflammation is often associated with disturbed performance of beta-cells and
      insulin resistance, the cardinal metabolic event of type-2 diabetes. Feline
      diabetes mellitus shares many similarities with type-2 diabetes in humans. Our
      objective was to elucidate the role of TLRs in feline pancreatic islets and islet
      like clusters (ILC) that consist of islets with their adjacent tissue. We tested
      whether TLRs are triggered by their agonists and lead to the expression of
      inflammatory cytokines. We confirmed the expression of all known feline TLRs in
      pancreas and ILC. Furthermore, stimulation with TLR agonists increased IL-6 mRNA
      and protein content and the expression of other proinflammatory cytokines
      indicating a clear proinflammatory response. The reactivity to TLR ligands was
      stronger in beta-cell enriched populations obtained after sorting by FACS
      indicating that inflammatory stimuli can also be generated within beta-cells. We
      conclude that the microenvironment of feline beta-cells harbor the potential for
      inflammatory reactions, that can be initiated by molecules released from bacteria
      or viruses or other molecules recognized by TLRs. Therefore infections associated
      with bacteriemia and viremia can induce inflammation in islets and damage the
      endocrine pancreatic tissue.

PMID- 20674990
TI  - Preclinical models of antipsychotic drug-induced metabolic side effects.
AB  - Antipsychotic drugs (APDs), and the 'atypical' APDs in particular, are commonly
      associated with metabolic side effects in humans. These include glucose
      dysregulation, insulin resistance, hyperlipidemia, weight gain and hypertension,
      which put patients at increased risk of cardiometabolic disorders. The underlying
      biology of APD-induced side effects in humans is poorly understood, and therefore
      preclinical rodent models are essential for translational research. With numerous
      recent studies on the topic, there is an emerging consensus that some symptoms,
      such as glucose dysregulation and insulin resistance, are more reliably observed
      than others, such as weight gain and hypertension, but, comparison between
      preclinical studies is complicated by numerous factors, including drug-specific
      effects and variables such as diet and treatment regimen. In this paper, we
      provide a major review of this important and growing field of preclinical study,
      and address crucial issues for future research.

PMID- 20674991
TI  - Domoic acid uptake and elimination kinetics in oysters and mussels in relation to
      body size and anatomical distribution of toxin.
AB  - Toxin accumulation by suspension-feeding qualifier depends on a balance between
      processes regulating toxin uptake (i.e. ingestion and absorption of toxic cells)
      and elimination (i.e. egestion, exchange among tissues, excretion, degradation
      and/or biotransformation) during exposure to toxic blooms. This laboratory study
      compares the size-specific uptake and elimination kinetics of domoic acid (DA)
      from Pseudo-nitzschia multiseries in two co-occurring bivalves, the oyster
      Crassostrea virginica and the mussel Mytilus edulis. Domoic acid concentrations
      were measured in visceral and non-visceral tissues of different-sized oysters and
      mussels during simultaneous long-term exposure to toxic P. multiseries cells in
      the laboratory, followed by depuration on a non-toxic algal diet. Mussels
      attained 7-17-fold higher DA concentrations than oysters, depending on the body
      size and exposure time, and also detoxified DA at higher rates (1.4-1.6 d(-1))
      than oysters (0.25-0.88 d(-1)) of a comparable size. Small oysters attained
      markedly higher weight-specific DA concentrations (maximum=78.6 MUg g(-1)) than
      large, market-sized individuals (<= 13 MUg g(-1)), but no clear relationship was
      found between body size and DA concentration in mussels (maximum=460 MUg g(-1)).
      Therefore, differential DA accumulation by the two species was, on average,
      approximately 3-fold more pronounced for large bivalves. An inverse relationship
      between DA elimination rate and body size was established for oysters but not
      mussels. Elimination of DA was faster in viscera than in other tissues of both
      bivalves; DA exchange rate from the former to the latter was higher in oysters.
      The contribution of viscera to the total DA burden of mussels was consistently
      greater than that of other tissues during both uptake (>80%) and depuration
      (>65%) phases, whereas it rapidly decreased from 70-80% to 30-40% in oysters, and
      this occurred faster in smaller individuals. Residual DA concentrations (<= 0.25
      MUg g(-1)) were detected at later depuration stages (up to 14 d), mainly in
      viscera of oysters and non-visceral tissues of mussels, suggesting that a second,
      slower-detoxifying toxin compartment exists in both species. However, a simple
      exponential decay model was found to adequately describe DA elimination kinetics
      in these bivalves. The lower capacity for DA accumulation in oysters compared to
      mussels can thus only be explained by the former's comparatively low toxin intake
      rather than faster toxin elimination.

PMID- 20674992
TI  - Iron deficiency activates pro-inflammatory signaling in macrophages and foam
      cells via the p38 MAPK-NF-kappaB pathway.
AB  - BACKGROUND/OBJECTIVES: Major bleeding in patients with acute coronary syndrome
      (ACS) increases the risk of recurrent ACS and mortality. However, the mechanism
      involved is poorly understood. Bleeding induces iron deficiency. Iron deficiency
      enhances inflammation in other diseases. Thus, in this paper, the particular
      effect of iron deficiency on atherosclerotic plaque destabilization, especially
      the pro-inflammatory role of iron deficiency in atheroma and the mechanism
      involved were investigated. METHODS: Extracellular matrix metalloproteinase
      inducer (EMMPRIN) and matrix metalloproteinase-9 (MMP-9) mRNA levels were
      investigated by RT-PCR. EMMPRIN and MMP-9 protein levels, nuclear factor (NF)
      kappaB-p65 protein levels, peroxisome proliferator-activated receptor gamma
      (PPARgamma) protein levels, and mitogen-activated protein kinase (MAPK)
      phosphorylation were determined by western blotting. MMP-9 enzymatic activity was
      assayed by gelatin zymography. RESULTS: Iron deficiency enhanced EMMPRIN, MMP-9
      production, and MMP-9 enzymatic activity in THP-1 derived macrophages and foam
      cells. Iron deficiency elicited the activation of NF-kappaB and p38 MAPK. By
      using the p38 inhibitor and NF-kappaB inhibitor, the study established that
      EMMPRIN and MMP-9 inductions by iron deficiency required the consecutive upstream
      activation of p38 MAPK and NF-kappaB. This pro-inflammatory action was not
      prevented by PPARgamma agonist. Meanwhile, iron deficiency did not modulate
      PPARgamma expression. Retinoid X receptor agonist suppressed the effects of iron
      deficiency on EMMPRIN , MMP-9, and NF-kappaB, but not on MAPK activation.
      CONCLUSIONS: Iron deficiency enhances atheroma inflammation through p38 MAPK-NF
      kappaB-EMMPRIN/MMP-9 pathway. Our findings provide a potential mechanism for the
      association of major bleeding with recurrent ACS and mortality in patients with
      ACS.

PMID- 20674993
TI  - Glucometabolic responses during Glucose Tolerance Test: a comparison between
      known diabetes and newly detected diabetes after acute myocardial infarction.
AB  - BACKGROUND: Glucose Tolerance Test (GTT) newly detects diabetes (new diabetes) in
      a substantial number of patients without a history of diabetes (known diabetes)
      after acute myocardial infarction (AMI). Patients with new diabetes have poor
      outcomes, despite their lower HbA1c levels. METHODS: This study consisted of 53
      patients with new diabetes and 47 patients with known diabetes who underwent GTT
      1 week after AMI. Sixty-eight patients with normal GTT and 78 patients with
      impaired glucose tolerance served as control. Plasma glucose and insulin were
      measured at fasting, 30 m, 60 m and 120 m after glucose load. Peak glucose
      fasting glucose was used as a measure of glucose fluctuation. Homeostasis model
      assessment of insulin resistance and the Stumvoll's equations were used to assess
      insulin sensitivity and beta-cell function, respectively. RESULTS: Fasting
      glucose (115 +/- 20 mg/dl versus 129 +/- 41 mg/dl, p=0.02) and hemoglobin A1C
      (5.7 +/- 0.5% versus 6.7 +/- 1.4%, p<0.001) in new diabetes were significantly
      lower than known diabetes. Insulin sensitivity was similarly impaired in both new
      diabetes and known diabetes (3.2 +/- 2.2 versus 3.0 +/- 1.9, p=0.58). Impairment
      of insulin secretion was less severe in new diabetes than in known diabetes. Peak
      glucose-fasting glucose was significantly greater in diabetic patients than
      inpatients with normal GTT (75 +/- 30 mg/dl, p<0.001) and impaired glucose
      tolerance (95 +/- 24 mg/dl, p<0.001), with no difference between new diabetes and
      known diabetes (156 +/- 36 mg/dl versus 165 +/- 57 mg/dl, p=0.36). CONCLUSIONS:
      These findings suggested that insulin resistance and exaggerated glucose
      fluctuation could be attributable to poor outcomes after AMI in patients with new
      diabetes.

PMID- 20674994
TI  - Likelihood of obstructive coronary disease in metabolic syndrome patients with
      abnormal stress echocardiography.
AB  - BACKGROUND: Metabolic syndrome (MetSx) encompasses several risk factors for
      macrovascular coronary artery disease. An association between MetSx and coronary
      syndrome X has also been reported, suggesting that patients with MetSx are more
      likely to have endothelial dysfunction in the setting of angiographically normal
      coronary arteries. It remains unknown whether MetSx patients with abnormal stress
      echocardiography (SE) are more likely to have obstructive coronary disease (CAD)
      compared to patients without MetSx. METHODS: We identified symptomatic patients
      without known CAD and abnormal SE who underwent coronary angiography within 4
      weeks after the SE. Patients were grouped according to their MetSx and impaired
      fasting glucose (IFG) status. We compared the proportion of patients with
      obstructive CAD in each subgroup using the x(2) test. Multivariate regression
      analysis was used to adjust for the pre-test probability of underlying coronary
      artery disease. RESULTS: Among 583 consecutive symptomatic patients who had an
      abnormal SE and were referred for angiography, 158 (36%) met the NCEP definition
      of MetSx. MetSx patients had a trend towards having more obstructive CAD than
      those without MetSx (OR 1.44, p = 0.07). After adjusting for pre-test probability
      of coronary disease, smoking and LDL-C, MetSx/IFG combination was an independent
      predictor of obstructive CAD (OR 2.06 [1.24-3.44], p < 0.001) but MetSx with
      normal fasting blood glucose was not (OR 0.91 [0.47-1.70], p 0.09). CONCLUSION:
      Symptomatic patients with MetSx and IFG are more likely to have angiographically
      significant CAD after abnormal SE than patients without MetSx or those with
      normal fasting blood glucose.

PMID- 20674995
TI  - Autonomic nervous system dysfunction in advanced systolic heart failure.
AB  - BACKGROUND: An alteration of the autonomic nervous system has been described in
      heart failure (HF). The aim of this study was to assess, compare and relate the
      impairment of both arms of the autonomic nervous systems, the sympathetic and
      parasympathetic (SNS and PNS) in a same group of patients. METHODS: We analyzed
      23 patients with advanced HF (NYHA III-IV/IV and IV/IV) and EF<35% who were on
      the waiting list for heart transplantation. We assessed the SNS by determining
      cardiac uptake of (123)I metaiodobenzylguanidine, and analyzed the heart
      mediastinum rate (HMR) and the myocardial washout rate (WR). The PNS was assessed
      by 24-hour Holter ECG recording and subsequent analyses of heart rate turbulence
      (HRT) in which turbulence onset (TO) and turbulence slope (TS) were determined.
      RESULTS: In the study of the SNS, HMR values were 1.32 +/- 0.12, and WR 0.36 +/-
      0.1. Higher creatinine levels were associated with a lower WR (r=-0.604; p=0.02).
      In the study of the SNP, TO was higher the lower the LVEF (r=-0.410; p=0.052),
      and age was associated with a lower TS (r=-0.4; p=0.059). In the study of the
      relationships between the SNS and PNS, HMR was correlated in a nearly significant
      manner with TO (r=-0.399; p=0.059) and WR with TS (r=-0.447; p=0.033).
      CONCLUSIONS: In stable patients with advanced HF (NYHA III-IV and IV/IV), a
      significant and parallel impairment occurs in both arms of the autonomic nervous
      system. This could have prognostic implications and would help to prioritize
      patients on the waiting list for heart transplantation.

PMID- 20674996
TI  - Acidic and basic fibroblast growth factors involved in cardiac angiogenesis
      following infarction.
AB  - Acidic and basic fibroblast growth factors (FGF-1/FGF-2) promote angiogenesis in
      cancer. Angiogenesis is integral to cardiac repair following myocardial
      infarction (MI). The potential regulation of FGF-1/FGF-2 in cardiac angiogenesis
      postMI remains unexplored. Herein, we examined the temporal and spatial
      expression of FGF-1/FGF-2 and FGF receptors (FGFR) in the infarcted rat heart at
      days 1, 3, 7, and 14 postMI. FGF-1/-2 gene and protein expression, cells
      expressing FGF-1/-2 and FGFR expression were examined by quantitative in situ
      hybridization, RT-PCR; western blot, immunohistochemistry and quantitative in
      vitro autoradiography. Compared to the normal heart, we found that in the border
      zone and infarcted myocardium 1) FGF-1 gene expression was increased in the first
      week postMI and returned to control levels at week 2; FGF-1 protein levels were,
      however, largely reduced at day 1, then elevated at day 3 peaked at day 7 and
      declined at day 14; and cells expressing FGF-1 were primarily inflammatory cells;
      2) FGF-2 gene expression was significantly elevated from day 1 to day 14; the
      increase in FGF-2 protein level was most evident at day 7 and cells expressing
      FGF-2 were primarily endothelial cells; 3) FGFR expression started to increase at
      day 3 and remained elevated thereafter; and 4) FGF-1/FGF-2 and FGFR expression
      remained unchanged in the noninfarcted myocardium. Thus, FGF-1/FGF-2 and FGFR
      expression are enhanced in the infarcted myocardium in the early stage after MI,
      which is spatially and temporally coincident with angiogenesis, suggesting that
      FGF-1/FGF-2 are involved in regulating cardiac angiogenesis and repair.

PMID- 20674997
TI  - Mesenchymal stem cell injection ameliorates the inducibility of ventricular
      arrhythmias after myocardial infarction in rats.
AB  - BACKGROUND: Mesenchymal stem cell transplantation is a promising new therapy to
      improve cardiac function after myocardial infarction (MI). The
      electrophysiological consequences of MSC implantation has not been systematically
      studied. METHODS: We investigated the electrophysiological and arrhythmogenic
      effects of mesenchymal stem cells (MSCs) therapy in experimental infarction
      model. Rats were subjected to MI operation by LAD ligation and randomly allocated
      to receive intramyocardially injection PBS (MI-PBS) or 5 * 10(5) EGFP labeled
      MSCs (MI-MSCs). Electrophysiological study, histological examination, and western
      blotting were performed 2 weeks after cell transplantation. RESULTS: Programmed
      electrical stimulation (PES) showed a significant reduced inducible ventricular
      tachycardias (VTs), raised ventricular fibrillation threshold (VFT) and prolonged
      ventricular effective refractory period (VERP) in MSC-treated rats compared to
      PBS-treated animals. MSC implantation led to markedly longer action potential
      duration (APD) and shorter activation time (AT) in infarcted border zone (IBZ) of
      left ventricular epicardium compared with PBS-treated hearts. Histological study
      revealed that fibrotic area and collagen deposition in infarcted region were
      significantly lower in MI-MSC group than in MI-PBS group. Abnormal alterations of
      Connexin 43 including reduction and lateralization were significantly attenuated
      by MSC treatment. CONCLUSIONS: This study provide strong evidence that MSC
      implantation ameliorates interstitial fibrosis and the remodeling of gap
      junction, attenuates focal heterogeneity of reporlarization and conduction and
      reduces vulnerability to VTs. The results suggest that MSC transplantation might
      emerge as a new preventive strategy against VAs besides improving cardiac
      performance in ischemic heart disease.

PMID- 20674998
TI  - Mortality in adult congenital heart disease: are national registries reliable for
      cause of death?
AB  - BACKGROUND: Statistics on cause-specific mortality are important for prognostic
      research. The aim of this study was to assess the utility of the national
      mortality registry in research on causes of death in adult patients with
      congenital heart disease (CHD). METHODS: The CONCOR registry of over 10,000
      adults with CHD was used to verify the causes of death provided by the WHO
      guidelines based national mortality registry, by linkage. RESULTS: Of 7277
      patients linked to the national mortality registry, 196 (2.4%) were recorded
      deceased, versus 228 deceased patients (3.1%) recorded in the CONCOR registry,
      during a follow-up of 25,900 patient years. Median age at death was 48.9 years.
      Of all deaths in the CONCOR registry, 77% had a cardiovascular origin; nearly 50%
      were due to progressive heart failure and arrhythmias. The national mortality
      registry recorded death due to progressive heart failure and arrhythmias in only
      8.5%. Moreover, this registry recorded death with an 'unspecified' cause in
      approximately 30%, primarily containing patients who died due to progressive
      heart failure and arrhythmias according to their medical records. CONCLUSION: WHO
      guidelines based national mortality registries lack the specificity and
      completeness needed for accurate research on causes of death in adult patients
      with CHD.

PMID- 20674999
TI  - Clinical implications of switching from intensive to moderate statin therapy
      after acute coronary syndromes.
AB  - BACKGROUND AND AIMS: Intensive statin therapy represents an effective option
      after acute coronary syndromes (ACS). Despite evidence, switching to less
      effective statins frequently occurs in practice. Aim of this observational study
      was to assess the impact of switching from intensive to moderate statin therapy
      on clinical outcomes after ACS. METHODS AND RESULTS: A cohort of 1321 consecutive
      ACS patients (886 men, age 71 +/- .8 years) discharged on atorvastatin 80 mg/d in
      a 6.5 year period was followed for 12 months after discharge. During follow-up,
      557 patients (42%) were switched by primary care physicians to moderate statin
      therapy, either for side effects (56%) or for safety concerns (44%). No major
      adverse reaction was reported. Increasing age (HR 1.52 per 10-year increase, 95%
      CI 1.23-1.78, p=0.01), and female gender (HR 1.11, 95% CI 1.06-1.23, p=0.02) were
      associated with a higher probability of switch. Patients following a cardiac
      rehabilitation program (HR 0.64 95% CI 0.49-0.86, p=0.02) and diabetic subjects
      (HR 0.81, 95% CI 0.67-0.92, p=0.02) were more likely to continue atorvastatin 80
      mg/d. During follow-up, a major adverse clinical event occurred in 331 patients
      (one-year probability 0.25, 95% CI 0.22-0.27). Multivariate analysis with Cox
      proportional hazards method, including statin switching as a time-dependent
      covariate, demonstrated that, after adjustment for demographic and clinical
      variables, reduction from intensive to moderate statin therapy was an independent
      predictor of adverse clinical outcomes (HR 2.7, 95% CI 1.7-5.1, p=0.004).
      CONCLUSION: Switching from intensive to moderate statin therapy after ACS is
      associated with an increased incidence of adverse clinical events.

PMID- 20675000
TI  - The prevalence and risk factors for cholelithiasis and asymptomatic gallstones in
      adults with congenital heart disease.
AB  - PURPOSE: Cyanosis is considered to be a risk factor for cholelithiasis which is
      an important complication of cyanotic congenital heart disease (CCHD) in adults.
      In this study, the prevalence of cholelithiasis and asymptomatic calcium
      bilirubinate gallstones was evaluated in adults with congenital heart disease
      (CHD). Furthermore, risk factors for this potentially high risk complication were
      assessed. MATERIALS AND METHODS: Subjects were derived from 114 consecutive
      congenital patients who visited our center from May 2008 to January 2009. For
      analyses of risk factors, we divided them into 4 groups: group A, 15 CCHD
      patients without reparative surgery (7 men, 31.8 +/- 7.0 years old); group B, 41
      CCHD patients rendered acyanotic by reparative surgery (21 men, 32.5 +/- 11.8
      years old); group C, 23 unoperated acyanotic CHD patients (11 men, 42.4 +/- 16.4
      years old); and group D, 35 patients who were acyanotic before and after
      operation (18 men, 36.3 +/- 14.8 years old). Gallstones were identified by
      abdominal ultrasound and risk factors were analyzed by a multivariate logistic
      regression model. RESULTS: Cholecystectomy was performed in 5/114 (4.3%),
      asymptomatic gallstones were seen in 16/114 (14%), and symptomatic gallstones
      except for patients after cholecystectomy were seen in 7/114 (6.1%). In group A,
      4 (27%) with gallstones underwent cholecystectomy (p<0.01). Non-cholesterol
      gallstones were observed in 5 patients (33%) in group A, 12 patients (29%) in
      group B, nobody in group C, and 3 patients (8.6%) in group D. By a multivariate
      logistic regression model, CCHD by nature regardless of repair, prolonged
      cyanosis periods, higher frequency of cardiopulmonary bypass (CPB), and lower
      platelet counts were significant factors predicting gallstones (odds ratio 4.48,
      1.08, 3.96, and 0.87, 95% CI, 1.14-17.5, 1.00-1.18, 1.65-9.54, and 0.75-0.99,
      respectively). CONCLUSIONS: The prevalence of cholelithiasis and asymptomatic
      gallstones is significantly high in CCHD patients regardless of cardiac repairs.
      CCHD by nature, prolonged cyanosis durations, high frequency of CPB and low
      platelet counts have influences on gallstone formation in adults with CHD.

PMID- 20675001
TI  - Relation of flow-mediated dilation to global arterial load: impact of
      hypertension and additional cardiovascular risk factors.
AB  - BACKGROUND: Endothelial dysfunction may be related to increased left ventricular
      (LV) mass due to an association between endothelial dysfunction with increased
      arterial load. Therefore, we evaluated whether brachial artery flow-mediated
      dilation (FMD) is related to global arterial load. METHODS: Pulse pressure/stroke
      index (PP/SVi, global arterial stiffness, prognostically validated), stroke
      volume/PP (SV/PP, global arterial compliance), and % of the predicted SV/PP by
      heart rate, age and body weight (confounder-adjusted global compliance,
      prognostically validated) were used as LV geometry-related indices of global
      arterial load. RESULTS: Compared to normotensive participants (NT, n = 50), those
      with hypertension (HTN, n = 51) had lower FMD (8.3% +/- 5.4 vs. 12.8% +/- 6.5),
      higher PP/SVi (1.24 +/- 0.34 vs. 1.04 +/- 0.28 mmHg m(2)/ml), higher LV mass and
      higher relative wall thickness (all p < 0.01); in contrast, SV/PP and % of
      predicted SV/PP did not differ between NT and HTN (all p>0.1). Impaired FMD was 3
      4-fold more prevalent than LV hypertrophy or increased arterial load both in NT
      and in HTN. Within NT and HTN separately, PP/SVi, SV/PP and % of predicted SV/PP
      were comparable among tertiles of FMD. Only in NT, lower FMD was associated with
      higher peak exercise systolic BP (p < 0.05). In multivariable regression models,
      FMD was not associated with indices of arterial load independently (all p > 0.1).
      CONCLUSIONS: In young-to-middle-age subjects with cardiovascular risk factors,
      impaired FMD is more prevalent than traditional preclinical manifestation of
      cardiovascular disease, and may exist independent to increased arterial load.
      Thus, endothelial dysfunction assessment may refine cardiovascular risk profile
      and risk-reduction strategies based on detection of traditional target organ
      damage.

PMID- 20675002
TI  - Stability analysis of motion patterns in biathlon shooting.
AB  - The aim of this study was to analyze the stability of the aiming process of elite
      biathlon athletes. Nine elite athletes performed four series of five shots onto
      the same target and onto targets next to each other in a shooting hall. A video
      based system reconstructed the horizontal and vertical motion of the muzzle. The
      time period starting after repeating the rifle and ending with the shot was
      divided in 10 intervals of equal duration. Eight kinematic parameters describing
      the motion in these intervals were calculated. Based on the parameter values
      obtained a special variant of an artificial network of type SOM (self-organizing
      map) was trained. Similar neurons were combined to clusters. For each shot the 10
      data sets describing the aiming process were then mapped to the corresponding
      neurons. The sequence of the related clusters in the respective succession was
      used as representation of the complex aiming motion. In a second processing step
      types of shots were identified applying a second net. A more stable pattern could
      be inferred for the members of the national squad compared to the biathletes
      classified in the next best performance level. Only small differences between the
      two shooting conditions could be observed.

PMID- 20675004
TI  - Aspirin for people with diabetes: a misleading inference in a recent meta
      analysis?

PMID- 20675003
TI  - Micro-array for the identification of Shiga toxin-producing Escherichia coli
      (STEC) seropathotypes associated with Hemorrhagic Colitis and Hemolytic Uremic
      Syndrome in humans.
AB  - A micro-array has been developed, based on the GeneDisc(R) array, for the genetic
      identification of 12 O-types and 7 H-types of Shiga toxin-producing Escherichia
      coli (STEC) including the most clinically relevant enterohemorrhagic E. coli
      (EHEC) serotypes. The genes selected for determination of the O antigens
      (rfbE(O157), wzx(O26), wzx(O103), wbd1(O111), ihp1(O145), wzx(O121), wzy(O113),
      wzy(O91), wzx(O104), wzy(O118), wzx(O45), and wbgN(O55)) and H-types (fliC(H2),
      fliC(H7), fliC(H8), fliC(H11), fliC(H19), fliC(H21), and fliC(H28)) showed a high
      specificity and concordance with serology. The micro-array also had a high
      specificity for EHEC-associated virulence factors, including Shiga toxins 1 and 2
      (stx1 and stx2), intimin (eae), enterohemolysin (ehxA), serine protease (espP),
      catalase peroxidase (katP), the type II secretion system (etpD), subtilase
      cytotoxin (subA), autoagglutinating adhesin (Saa) and type III secreted effectors
      encoded in the genomic islands OI-122 (ent/espL2, nleB, and nleE) and OI-71
      (nleF, nleH1-2, and nleA). The eae gene was detected in all typical EHEC strains,
      and the pattern of nle genes encoded in OI-71 and OI-122 was found to be closely
      associated with certain serotypes of typical EHEC and emerging EHEC strains.
      Virulence plasmid associated genes such as katP, espP, and etpD were more common
      in EHEC than in STEC strains; this supports their association with virulence.
      This array constitutes a valuable approach for the identification of STEC strains
      with a high potential for human virulence.

PMID- 20675005
TI  - Glucose intolerance and cardiovascular risk factors in Hong Kong: data from two
      occupation-based cross-sectional surveys.
AB  - AIMS: To examine the distribution of plasma glucose and related cardiovascular
      risk factors in two occupation-based cross-sectional surveys in a Chinese ethnic
      population. METHODS: Two cross-sectional surveys in a Hong Kong working
      population. In 1990, 1496 participants aged 18-66 years underwent an OGTT,
      anthropometric, and other biochemical measures. Identical measures were collected
      from 534 participants aged 20-72 years in 2001-2003. Data were direct age
      standardised to compare CVD risk factor prevalence. Linear regression modelling
      was used to examine the distribution of continuous CVD risk factors. RESULTS:
      Mean (SD) 2-h plasma glucose values were 5.6mmol/l (2.1) in 1990 and 6.5mmol/l
      (2.5) in 2001-2003, an apparent increase of 0.5mmol/l (95% CI 0.3 to 0.7,
      p<0.001) after age and sex adjustment. However, there was no significant
      difference in the age-standardised prevalence of glucose intolerance, overweight
      or obesity. There were significantly smaller proportions of women with
      hypertension and hyperlipidaemia and male smokers in the second compared to the
      first survey. CONCLUSIONS: We observed a relatively adverse glycaemia profile,
      which may have worsened over time, in two healthy populations of survey
      respondents, with comparatively low rates of most CVD risk factors. This has
      implications for the future burden of disease associated with hyperglycaemia in
      this population.

PMID- 20675006
TI  - Phosphatidylinositol-3-kinase p110gamma contributes to bile salt-induced
      apoptosis in primary rat hepatocytes and human hepatoma cells.
AB  - BACKGROUND & AIMS: Glycochenodeoxycholate (GCDC) and taurolithocholate (TLC) are
      hepatotoxic and cholestatic bile salts, whereas tauroursodeoxycholate (TUDC) is
      cytoprotective and anticholestatic. Yet they all act, in part, through
      phosphatidylinositol-3-kinase(PI3K)-dependent mechanisms ("PI3K-paradox").
      Hepatocytes express three catalytic PI3K Class I isoforms (p110alpha/beta/gamma),
      specific functions of which, in liver, are unclear. In other cell types,
      p110gamma is associated with detrimental effects. To shed light on the PI3K
      enigma, we determined whether hydrophobic and hydrophilic bile salts
      differentially activate distinct p110 isoforms in hepatocytes, and whether
      p110gamma mediates bile salt-induced hepatocyte cell death. METHODS: Isoform
      specific PI3K activity assays were established to determine isoform activation by
      bile salts in rat hepatocytes. Activation of Akt and JNK was determined by
      immunoblotting. Following stimulation with hydrophobic bile salts, hepatocellular
      apoptosis was determined morphologically after Hoechst staining and by analysis
      of caspase-3/-7 activity or caspase-3 cleavage. Activity or expression of PI3K
      p110gamma was inhibited pharmacologically (AS604850) or by knock-down using
      specific siRNA. RESULTS: All bile salts tested activated p110beta, while
      p110alpha was activated by TUDC and GCDC. Intriguingly, only hydrophobic bile
      salts activated p110gamma. Inhibition of p110gamma attenuated GCDC-induced Akt-
      and JNK-activation, but did not alter TUDC- or cAMP-induced Akt-signaling in rat
      hepatocytes. Inhibition or knock-down of p110gamma markedly attenuated
      hydrophobic bile salt-induced apoptosis in rat hepatocytes and human hepatoma
      cell lines but did not alter Fas-, tumor necrosis factor alpha- and etoposide
      induced apoptosis. Depletion of Ca(++) prevented GCDC-induced toxicity in rat
      hepatocytes but did not affect GCDC-induced Akt- and JNK-activation. CONCLUSIONS:
      PI3K p110gamma is activated by hydrophobic, but not hydrophilic bile salts. Bile
      salt-induced hepatocyte apoptosis is partly mediated via a PI3K p110gamma
      dependent signaling pathway, potentially involving JNK.

PMID- 20675007
TI  - Fibroblast growth factor 21 levels are increased in nonalcoholic fatty liver
      disease patients and are correlated with hepatic triglyceride.
AB  - BACKGROUND & AIMS: Fibroblast growth factor 21 (FGF21), a hormone primarily
      secreted by the liver in response to peroxisome proliferator-activated receptor
      alpha (PPARalpha) activation, has recently been shown to possess beneficial
      effects on lipid metabolism and hepatic steatosis in animal models. This study
      investigated the association of FGF21 with nonalcoholic fatty liver disease
      (NAFLD) in Chinese patients. METHODS: Serum FGF21 levels were determined by
      enzyme-linked immunosorbent assay (ELISA) in 224 NAFLD and 124 control subjects,
      and their association with parameters of adiposity, glucose, and lipid profiles
      and levels of liver injury markers was studied. Besides serum concentrations, the
      mRNA expression of FGF21 in the liver tissue was also quantified by real-time PCR
      in 17 subjects with different degrees of steatosis, and was correlated with the
      levels of intrahepatic lipid. The protein levels of FGF21 were determined by
      quantitative ELISA. RESULTS: Serum FGF21 levels in patients with NAFLD (402.38
      pg/ml [242.03, 618.25]) were significantly higher than those in control subjects
      (198.62 pg/ml [134.96, 412.62]) (p<0.01). In human liver tissues, FGF21 mRNA
      expression increased with the degree of steatosis. Both FGF21 mRNA expression and
      serum FGF21 concentrations were positively correlated with intrahepatic
      triglyceride (TG) having r = 0.692 and r = 0.662, respectively, at p<0.01.
      Furthermore, the increased expression of FGF21 was accompanied by elevated
      protein levels in liver tissues. CONCLUSIONS: These results support the role of
      FGF21 as a key regulator of hepatic lipid metabolism in humans, and suggest that
      serum FGF21 can be potentially used as a biomarker for NAFLD.

PMID- 20675008
TI  - Role of small intestinal bacterial overgrowth and delayed gastrointestinal
      transit time in cirrhotic patients with minimal hepatic encephalopathy.
AB  - BACKGROUND & AIMS: Minimal hepatic encephalopathy (MHE) is the mildest form in
      the spectrum of hepatic encephalopathy. This cross-sectional study was carried
      out to elucidate the role of bacterial overgrowth of the small intestine and
      delayed intestinal transit among patients with MHE. METHODS: Two-hundred-thirty
      patients with cirrhosis were screened; 102 patients (44.4%) who met the
      eligibility criteria were included in the study. MHE was diagnosed when the
      psychometric hepatic encephalopathy score was <=-5. All patients underwent a
      glucose breath test for small intestinal bacterial overgrowth (SIBO) and
      lactulose breath test for oro-cecal transit time (OCTT). RESULTS: Fifty-seven
      (55.9%) patients with cirrhosis had MHE. Among these patients with MHE, 22
      (38.6%) had SIBO, while 4 (8.9%) without MHE had SIBO (p = 0.001). The prevalence
      of SIBO was higher in patients with CTP classes B and C (69.2%) compared to those
      in CTP class A (30.8%); p = 0.054. OCTT was significantly prolonged in patients
      who had SIBO than in those who did not have SIBO (p<0.0001). Univariate analysis
      demonstrated that increased age, female gender, low educational status, low
      albumin, presence of SIBO, and prolonged OCTT were associated with the presence
      of MHE. Multivariate analysis demonstrated SIBO as the only factor associated
      with MHE. CONCLUSIONS: Our study conclusively demonstrates high prevalence of
      SIBO in patients with cirrhosis with MHE. This study gives the rationale of
      treatment directed against SIBO and gut dysmotility, which may include non
      absorbable antibiotics such as rifaximin, probiotics, and prokinetics.

PMID- 20675009
TI  - Epigenetic inactivation of the tumor suppressor gene RIZ1 in hepatocellular
      carcinoma involves both DNA methylation and histone modifications.
AB  - BACKGROUND & AIMS: The retinoblastoma-interacting zinc finger gene RIZ1 is
      inactivated in many cancers, but the underlying mechanisms remain unknown. This
      study aimed to investigate the epigenetic mechanisms of RIZ1 inactivation by
      analyzing the relationship between DNA methylation and histone modifications
      during regulation of RIZ1 expression. METHODS: Methylation-specific PCR, RT-PCR,
      and immunohistochemistry were performed to examine RIZ1 methylation and
      expression. Dynamic changes in histone H3 lysine 9 (H3K9) modifications and
      histone deacetylases (HDACs) associated with the promoter were analyzed by
      chromatin immunoprecipitation (ChIP). RESULTS: RIZ1 methylation was detected in
      66.7% (32/48) HCC tissues, 6.3% (3/48) corresponding non-cancerous tissues, and
      66.7% (4/6) HCC cell lines. All 32 HCC tissues with promoter methylation showed
      complete loss of RIZ1 protein, whereas RIZ1 protein was present in all the
      corresponding non-cancerous tissues. Neither 5-aza-2-deoxycitidine (5-Aza-dC) nor
      Trichostatin A (TSA) reversed promoter methylation, but did restore RIZ1 mRNA and
      resulted in the downregulation of HDAC1 but not HDAC3. However, 5-Aza-dC+TSA
      induced a partial reversal of promoter methylation and a markedly synergistic
      reactivation of RIZ1. Moreover, both HDAC1 and HDAC3 were downregulated. The ChIP
      assays showed 5-Aza-dC and/or TSA also contributed to the dynamic conversion of
      trimethylated to acetylated H3K9 at the promoter. Furthermore, a decrease in H3K9
      trimethylation preceded an increase in H3K9 acetylation. CONCLUSIONS: Our results
      suggest that promoter methylation and H3K9 modifications work together to silence
      the RIZ1 gene in HCC. 5-Aza-dC can restore the expression of RIZ1, as reflected
      by its effects on histone modification levels. This finding indicates that
      cooperative effects between these epigenetic modifications exist.

PMID- 20675010
TI  - Changing patient consultation patterns in primary care: an investigation of
      uptake of the Minor Ailments Service in Scotland.
AB  - OBJECTIVES: To study the impact and potential predictors of uptake of patient
      registrations and supplied medicines under the Minor Ailments Scheme (MAS) in
      Scotland. The MAS was introduced in 2006, intending to improve health care access
      by re-directing patients from primary care to community pharmacies. METHODS:
      Numbers of dispensed MAS items and patient registrations were obtained for all
      community pharmacies in Scotland for the period 2006-2009. Local demographic and
      socioeconomic characteristics were attributed to community pharmacies as
      potential predictors of MAS service uptake. RESULTS: There were significantly
      more MAS registrations in community pharmacies located in the most deprived
      areas. MAS registrations in rural areas were significantly lower than in urban
      areas. Rates of MAS items supplied ranged from 219.9 to 3604.6 items per 10,000
      Health Board population in 2008/09. Urban pharmacies supplied 72.6 MAS items per
      month compared to 43.3 items per month by rural pharmacies. 96.7 items per month
      were supplied by pharmacies in the most deprived areas compared to 53.2 items per
      month in the least deprived areas. CONCLUSION: There has been geographical
      variation in uptake of the MAS service. Community pharmacies under multiple
      ownership engaged in MAS activity to a greater extent than independent
      pharmacies, with higher uptake in community pharmacies located in deprived and
      urban areas.

PMID- 20675011
TI  - Socio-economic determinants of mortality in Taiwan: combining individual and
      aggregate data.
AB  - There is a very large literature that examines the relationship between health
      and income. Two main hypotheses have been investigated: the income inequality
      hypothesis and the absolute income hypothesis. Most of previous studies that used
      mortality data have been criticized for estimating an aggregate model that does
      not account for non-linear links between health and income at the individual
      level. In this paper we follow a novel approach to avoid this bias, combining
      aggregate mortality data with individual-level data on socio-economic
      characteristics. We test the income inequality and absolute income hypotheses
      using county-level mortality data from Life Statistic of Department of Health and
      individual-level data from Taiwan census Family Income and Expenditure Survey
      (FIES) for 1976-2004. We find the evidence to support the absolute income
      hypothesis but not income inequality hypothesis in the case of the general
      population. We also find strong evidence that education does have significant
      effects on individuals' health and the estimates are not sensitive to income
      equivalent scales.

PMID- 20675012
TI  - Lineage-specific expansion of DNA-binding transcription factor families.
AB  - DNA-binding domains (DBDs) are essential components of sequence-specific
      transcription factors (TFs). We have investigated the distribution of all known
      DBDs in more than 500 completely sequenced genomes from the three major
      superkingdoms (Bacteria, Archaea and Eukaryota) and documented conserved and
      specific DBD occurrence in diverse taxonomic lineages. By combining DBD
      occurrence in different species with taxonomic information, we have developed an
      automatic method for inferring the origins of DBD families and their specific
      combinations with other protein families in TFs. We found only three out of 131
      (2%) DBD families shared by the three superkingdoms.

PMID- 20675013
TI  - Discrete event simulation of a proton therapy facility: a case study.
AB  - Proton therapy is a type of particle therapy which utilizes a beam of protons to
      irradiate diseased tissue. The main difference with respect to conventional
      radiotherapy (X-rays, gamma-rays) is the capability to target tumors with extreme
      precision, which makes it possible to treat deep-seated tumors and tumors
      affecting noble tissues as brain, eyes, etc. However, proton therapy needs high
      energy cyclotrons and this requires sophisticated control-supervision schema to
      guarantee, further than the prescribed performance, the safety of the patients
      and of the operators. In this paper we present the modeling and simulation of the
      irradiation process of the PROSCAN facility at the Paul Scherrer Institut. This
      is a challenging task because of the complexity of the operation scenario, which
      consists of deterministic and stochastic processes resulting from the
      coordination-interaction among diverse entities such as distributed automatic
      control systems, safety protection systems, and human operators.

PMID- 20675015
TI  - Large-scale screening of TARDBP mutation in amyotrophic lateral sclerosis in
      Japanese.
AB  - Mutations in TARDBP encoding TDP (TAR DNA binding protein)-43 have been reported
      in familial and sporadic amyotrophic lateral sclerosis (ALS), but mostly in
      Caucasians. In other ethnic groups, four types of mutations are found in familial
      ALS. In sporadic ALS, the TARDBP mutations frequency is low in Caucasians (0-5%)
      and no mutation has been found in other ethnic groups. To examine spectrum of
      TARDBP mutations and its frequency in Japanese, we screened the TARDBP mutation
      in 721 Japanese ALS by direct sequencing. We identified a novel mutation, c.1069G
      > A (p.Gly357Ser) and a known mutation in sporadic ALS. One patient was
      homozygous for p.Gly357Ser, which was the first for TARDBP mutation. Our study
      showed that TARDBP mutations also occur in non-Caucasian sporadic ALS. The
      estimated frequency of the TARDBP mutation in sporadic ALS is 0.29% in Japanese.
      The mutation frequency in familial ALS in Japanese is also similar to that in
      Caucasian, and is ~10 times higher than that in Japanese sporadic ALS.

PMID- 20675014
TI  - Use of warfarin therapy at a target international normalized ratio of 3.0 for
      cutaneous polyarteritis nodosa.
AB  - BACKGROUND: Cutaneous polyarteritis nodosa (CPN) is an uncommon disorder that can
      be difficult to manage effectively. We have previously suggested that CPN might
      be associated with the presence of anti-phosphatidylserine-prothrombin complex
      (anti-PS/PT) antibodies, members of the antiphospholipid antibody family.
      OBJECTIVE: To evaluate clinical manifestations and effective treatments of CPN.
      METHODS: We conducted a retrospective analysis of three patients with CPN who
      responded to warfarin therapy. IgG and IgM anti-PS/PT antibodies were measured
      with a specific enzyme-linked immunosorbent assay. RESULTS: There was a dramatic
      improvement in our three CPN patients following warfarin therapy adjusted to a
      target international normalized ratio (INR) of about 3.0. Active disease
      progression was halted by sustained warfarin therapy during which the patients
      experienced resolution of their skin manifestations. LIMITATIONS: A small number
      of cases were studied and the study design was retrospective. CONCLUSION: We
      propose that warfarin therapy at a target INR of roughly 3.0 could be effective
      for treating patients with CPN. We further believe that treatment with warfarin
      led to the effective attenuation of anti-PS/PT antibodies related to prothrombin,
      and improved the symptoms in our CPN patients.

PMID- 20675016
TI  - [Red blood cell transfusion increases tissue oxygenation and improves the
      clinical outcome (con)].

PMID- 20675017
TI  - [Coordination between primary and specialized care in gastroenterology is
      insufficient. A survey of gastroenterologists and general practitioners].
AB  - BACKGROUND AND OBJECTIVES: Collaboration between general practitioners (GPs) and
      specialists is considered crucial to provide high-quality healthcare. The
      objective of this study was to analyze the relationship between
      gastroenterologists and GPs in regional hospitals and their referring primary
      care centers in Catalonia (Spain). MATERIALS AND METHODS: A descriptive,
      observational, cross-sectional study was carried out using anonymous
      questionnaires between January and April 2008. RESULTS: A total of 314 surveys
      were administered (261 GPs and 53 gastroenterologists). The overall relationship
      was considered highly deficient or insufficient by 62.3% of gastroenterologists
      (95% CI, 47.9-74.9) and by 55.6% of GPs (95% CI, 49.3-61.7). More than half
      (56.6%) of the gastroenterologists did not know any GPs, or only a very few, and
      the situation was the same for 80.4% of GPs. Sixty-four percent of
      gastroenterologists considered that the quality of care for digestive diseases in
      primary care was highly deficient or insufficient while 21.1% of GPs considered
      that the care provided by gastroenterologists was highly deficient or
      insufficient. The perception of healthcare in both primary and specialized
      settings was substantially better when there was good interaction between
      gastroenterologists and GPs. CONCLUSIONS: Practitioners acknowledge that the
      degree of interaction between different levels of healthcare is insufficient.
      Moreover, gastroenterologists consider that the management of digestive diseases
      in primary care is deficient. Establishing a personal relationship between the
      two types of practitioners substantially improves mutual assessment.

PMID- 20675018
TI  - [Handling the therapeutic response from the tumor with PET].

PMID- 20675019
TI  - Synthesis and antifungal evaluation of novel triazole derivatives as inhibitors
      of cytochrome P450 14alpha-demethylase.
AB  - A series of 1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-substituted-2
      propanols (1a-v, 2a-w), which are analogues of fluconazole, have been designed
      and synthesized as the potential antifungal agents by the click reaction. Click
      reaction approach toward the synthesis of two sets of novel 1,2,3-triazolyl
      linked triazole antifungal derivatives 1a-v, 2a-w was achieved by Cu(I)-catalyzed
      1,3-dipolar cycloaddition of propargylated intermediate 8 with substituted
      azidomethyl benzene. The 1,2,3-triazolyl group was inserted into the side chain
      of the target molecule which can increase the antifungal activity of compounds.

PMID- 20675020
TI  - Iodine concentration in cow's milk and its relation with urinary iodine
      concentrations in the population.
AB  - BACKGROUND & AIMS: The importance of milk intake to the supply of dietary iodine
      is not fully known. We therefore undertook a study in Spain of the iodine
      concentration in cow's milk and the impact of the frequency of milk consumption
      on urinary iodine concentrations in three study populations. METHODS: We studied
      the iodine concentration in 362 samples of milk from 45 commercial brands and
      compared it with the milk iodine status in studies undertaken 17 years earlier.
      The epidemiologic studies were performed in three different places in the south
      of Spain: two in school-age children (N = 757 and N = 1205 children) and one in
      adults (N = 1051). A milk consumption questionnaire was given and urinary iodine
      concentrations measured. RESULTS: The mean concentration of iodine in the milk
      rose from 1991 (117 +/- 37 MUg/L) to 2008 (259 +/- 58 MUg/L) (P < 0.001). The
      iodine concentration was greater in skimmed milk (273 +/- 52 MUg/L) than in semi
      skimmed milk (254 +/- 57 MUg/L) or whole milk (251 +/- 61 MUg/L) (P < 0.0001).
      The winter samples had a greater concentration of iodine (270 +/- 55 MUg/L) than
      the summer samples (247 +/- 58 MUg/L) (P < 0.0001), independently of the type of
      milk. The urinary iodine concentrations in all three epidemiologic studies were
      significantly associated with the frequency of milk intake. CONCLUSIONS: The
      concentration of iodine in cow's milk has risen over recent years, and it is
      higher in skimmed milk. The results also show that cow's milk is a relevant
      source of dietary iodine.

PMID- 20675021
TI  - Re: P. Mehanna, J. Devine, J. McMahon, Lip split and mandibulotomy modifications
      [Br. J. Oral Maxillofac. Surg. 48 (2010) 314-315].

PMID- 20675022
TI  - Effects of maturation on the mechanical properties of regenerated and residual
      tissues in the rabbit patellar tendon after resection of its central one-third.
AB  - BACKGROUND: The central one-third portion of the patellar tendon is commonly used
      as a graft for the reconstruction of the anterior cruciate ligament. Although
      several studies have been carried out on mechanical properties of healing tendons
      in mature animals, there have been no studies on regenerated and residual tissues
      in the immature patellar tendon after the removal of its central portion.
      METHODS: An entire one-third defect was made in the patellar tendon of 2-, 3- and
      6-month-old rabbits. After 3 weeks, the tissue regenerated in the defect and the
      residual tissue were biomechanically and histologically evaluated. FINDINGS: The
      length of patellar tendons in 6-month-old animals after the resection of its
      central one-third was significantly longer than that in age-matched controls. The
      cross-sectional area of all operated tendons was significantly larger compared to
      age-matched controls. There were no significant effects of maturation on the
      mechanical properties of regenerated and residual tissues in operated tendons,
      although tensile strength and tangent modulus of normal tendons were
      significantly greater in 6-month rabbits than in immature ones. The histology of
      each of regenerated and residual tissues was similar in the three groups.
      INTERPRETATION: There were no remarkable effects of maturation on regenerated and
      residual tissues after the removal of the central one-third tendon. However, the
      strength and the modulus of normal tendons are significantly lower in immature
      patients than in mature ones. Therefore, surgeons should take account of the
      inferior mechanical properties of the tendon in skeletally immature patients at
      the time of surgeries for the reconstruction of the anterior cruciate ligament.

PMID- 20675023
TI  - An initiation-termination two-phase model of worrying.
AB  - Researchers have identified many factors that are associated with worrying,
      ranging from a verbal/left hemisphere bias to intolerance of uncertainty. This
      paper describes an initiation-termination (IT) two-phase model of worrying that
      attempts to comprehensively put together the many different pieces of the puzzle.
      The first phase of the model concerns the development of perceptions of threat,
      which initiates the process of worrying. The strength of a perceived threat is
      influenced by the perceived probability and cost of an undesirable future
      outcome, along with danger/risk salience. The second phase concerns acceptance of
      the prospect of an uncertain future threat, which terminates the process of
      worrying. Factors that play roles in this second phase include beliefs about the
      value of worrying, the desire for certainty, a perseverative-iterative style, and
      a sense of closure regarding one's role in trying to prevent or plan for the
      threat. The factors that play roles in these two phases are discussed, as are the
      implications of the model for conceptualizing, treating and conducting research
      on worrying.

PMID- 20675024
TI  - National poverty reduction strategies and HIV/AIDS governance in Malawi: a
      preliminary study of shared health governance.
AB  - The public health and development communities understand clearly the need to
      integrate anti-poverty efforts with HIV/AIDS programs. This article reports
      findings about the impact of the Poverty Reduction Strategy Paper (PRSP) process
      on Malawi's National HIV/AIDS Strategic Framework (NSF). In this article we ask,
      how does the PRSP process support NSF accountability, participation, access to
      information, funding, resource planning and allocation, monitoring, and
      evaluation? In 2007, we developed and conducted a survey of Malawian government
      ministries, United Nations agencies, members of the Country Coordination
      Mechanism, the Malawi National AIDS Commission (NAC), and NAC grantees (N = 125,
      90% response rate), seeking survey respondents' retrospective perceptions of NSF
      resource levels, participation, inclusion, and governance before, during, and
      after Malawi's PRSP process (2000-2004). We also assessed principle health sector
      and economic indicators and budget allocations for HIV/AIDS. These indicators are
      part of a new conceptual framework called shared health governance (SHG), which
      seeks congruence among the values and goals of different groups and actors to
      reflect a common purpose. Under this framework, global health policy should
      encompass: (i) consensus among global, national, and sub-national actors on goals
      and measurable outcomes; (ii) mutual collective accountability; and (iii)
      enhancement of individual and group health agency. Indicators to assess these
      elements included: (i) goal alignment; (ii) adequate resource levels; (iii)
      agreement on key outcomes and indicators for evaluating those outcomes; (iv)
      meaningful inclusion and participation of groups and institutions; (v) special
      efforts to ensure participation of vulnerable groups; and (vi) effectiveness and
      efficiency measures. Results suggest that the PRSP process supported
      accountability for NSF resources. However, the process may have marginalized key
      stakeholders, potentially undercutting the implementation of HIV/AIDS Action
      Plans.

PMID- 20675025
TI  - From mainstream to marginal? Trends in the use of Chinese medicine in China from
      1991 to 2004.
AB  - In many Western societies, alternative healing options, including Chinese
      medicine, have started to move from the marginal to mainstream. In China, Chinese
      medicine has been an established component in the official health care system,
      but its relevance and effectiveness have often been challenged in a society
      committed to modernization. Despite abundant speculation, little research has
      established empirical facts regarding the use of Chinese medicine in China. This
      paper uses a longitudinal dataset to examine the trends from 1991 to 2004, and
      explore the extent to which changing population demographic and socioeconomic
      characteristics contributed to the observed trends. It finds that in the formal
      medical sector, the use of Chinese medicine has contracted, particularly in
      cities. Changing population demographic and socioeconomic characteristics cannot
      entirely account for the contraction. Rather, shifts in cultural values and
      structural changes in the health care system may have led to the observed
      decline.

PMID- 20675026
TI  - You can't get anything perfect: "user perspectives on the delivery of cognitive
      behavioural therapy by telephone".
AB  - Remote psychotherapy services such as telephone-administered cognitive
      behavioural therapy (T-CBT) have the potential to provide effective psychological
      treatment whilst simultaneously maximising efficiency, lowering costs and
      improving access to care. However, a lack of research examining the acceptability
      of non face-to-face psychotherapy means that little is known about users'
      perceptions of these delivery models. This paper reports data from two
      qualitative evaluations of T-CBT delivered in the voluntary and occupational
      health sectors in the UK. It explores users' acceptance of T-CBT, contrasting
      initial socially-construed expectations with more positive regard derived from
      experiential norms. User satisfaction with T-CBT was mixed. However, the relative
      ease with which most participants adapted to telephone-based care was suggestive
      of a shared construct of mental health service provision that prioritised the
      accessibility and availability of services over the social, professional and
      medico-legal perspectives that conventionally promote the co-location of
      practitioner and client.

PMID- 20675028
TI  - [Multiple pulmonary embolisms caused by acrylic cement after vertebroplasty].

PMID- 20675027
TI  - Refining the visual-cortical hypothesis in category learning.
AB  - Participants produce steep typicality gradients and large prototype-enhancement
      effects in dot-distortion category tasks, showing that in these tasks to-be
      categorized items are compared to a prototypical representation that is the
      central tendency of the participant's exemplar experience. These prototype
      abstraction processes have been ascribed to low-level mechanisms in primary
      visual cortex. Here we asked whether higher-level mechanisms in visual cortex can
      also sometimes support prototype abstraction. To do so, we compared dot
      distortion performance when the stimuli were size constant (allowing some low
      level repetition-familiarity to develop for similar shapes) or size variable
      (defeating repetition-familiarity effects). If prototype formation is only
      mediated by low-level mechanisms, stimulus-size variability should lessen
      prototype effects and flatten typicality gradients. Yet prototype effects and
      typicality gradients were the same under both conditions, whether participants
      learned the categories explicitly or implicitly and whether they received trial
      by-trial reinforcement during transfer tests. These results broaden out the
      visual-cortical hypothesis because low-level visual areas, featuring retinotopic
      perceptual representations, would not support robust category learning or
      prototype-enhancement effects in an environment of pronounced variability in
      stimulus size. Therefore, higher-level cortical mechanisms evidently can also
      support prototype formation during categorization.

PMID- 20675029
TI  - [Solitary pulmonary nodule in a patient exposed to welding fumes].

PMID- 20675030
TI  - [Cost-effectiveness study of the diagnosis of pleural effusion in chest diseases
      outpatient clinic].
AB  - OBJECTIVE: To evaluate the diagnostic efficacy of pleural procedures, safety,
      delay and cost of the diagnosis of pleural effusion (PE) by analysing the
      parameters that are dependent on the area of patient management (outpatient or
      inpatient). PATIENTS AND METHODS: Prospective non-randomized study. Two groups
      were established depending on whether they were managed in a specific outpatient
      unit or as a conventional hospital inpatient, with the rest of the criteria being
      the same for the study of the PE. RESULTS: We included 60 outpatients and 34
      inpatients. The median number of visits as an outpatient was 2 (range 2-3), and
      the time an inpatient was hospitalized was 13 (range 7.7-25-2) days. The number
      of analytical and imaging studies was significantly higher in the inpatient
      group. There were no differences in the number of cytology and pleural biopsies,
      or complications between groups. There were no differences in time to performing
      computed tomography. The number of days until the pleural biopsy and the time
      until to obtain a diagnosis was lower in the outpatient group. Mean total cost
      for an outpatient was euro1.352 and euro9.793,2 for inpatients. CONCLUSIONS:
      Management of ambulatory diagnosis of PE patients is highly cost-effective. The
      effectiveness and safety of forms of the study is at least similar. In this
      study, the mean cost for a hospitalised inpatient for a PE was 7.2 times higher
      than outpatient management.

PMID- 20675031
TI  - Immediate-type drug hypersensitivity and associated factors in a general
      population.
AB  - BACKGROUND: Our aim was to assess the prevalence and associated risk factors of
      common hypersensitivity reactions to drugs in the adult population, for which
      limited data are available. METHODS: The data consisted of 1052 questionnaires
      obtained from adults. The questionnaires consisted of questions on immediate-type
      hypersensitivity reactions induced by drugs (itching, skin rash/hives, angio
      oedema, shortness of breath, hypotension, and loss of consciousness). The
      questionnaire added knowledge on physician's diagnosis of asthma, allergic
      rhinitis, eczema, and other chronic systemic diseases. RESULTS: The prevalence of
      self-reported drug hypersensitivity reactions was 11.8% for all reactions.
      Hypersensitivity reactions to analgesics were the most common (37.2%) followed by
      antibiotics (24.2%). Multivariate analysis showed that female gender (Odds Ratio
      (OR) 95% Confidence Interval (CI) (2.00 (1.25-3.21)), physician-diagnosed
      allergic rhinitis (3.03 (1.64-5.59)), and eczema (3.22 (1.87-5.53)) were
      associated with any type of drug hypersensitivity reactions. Itching was
      associated with allergic rhinitis (4.50 (2.06-9.81)) and eczema diagnosis (4.24
      (2.14-8.64)). Skin rash/hives were associated with female gender (2.67 (1.24
      5.74)), allergic rhinitis (4.57 (1.99-10.05)), and eczema (5.36 (2.65-10.84)).
      Angio-oedema was higher in females (5.74 (1.69-18.5)). In addition, eczema (2.87
      (1.12-7.32)) and systemic hypertension (2.60(1.03-6.10)) were associated with
      angio-oedema. Shortness of breath was only associated with ever asthma diagnosis
      (6.59 (2.09-20.83)). Factors associated with loss of consciousness were female
      gender (5.56 (1.27-24.30)), allergic rhinitis diagnosis (4.76 (1.73-13.14)), and
      systemic hypertension (2.74 (1.02-7.41)). CONCLUSION: The study showed that
      females and subjects with allergic diseases and hypertension were more
      susceptible to drug hypersensitivity reactions.

PMID- 20675032
TI  - Diethyltoluamide (DEET) increases CD63 expression in a contact urticaria
      patient's basophils.

PMID- 20675033
TI  - Cystic fibrosis, atopy, asthma and ABPA.
AB  - The role of atopy on cystic fibrosis (CF) progression remains unclear but
      evidence suggests that it may influence the appearance of co-morbid conditions
      such as CF asthma or allergic bronchopulmonary aspergillosis (ABPA). Recognising
      asthma in patients with CF is not always easy but the identification of atopic
      markers favours the diagnosis. Physicians should be aware of this fact in order
      to achieve a better control of respiratory symptoms in patients with CF.
      Bronchial mucosa inflammation and abnormal mucus predispose to mould
      colonisation. These patients are at higher risk of allergic sensitisation,
      especially when atopic susceptibility is present. In the particular case of A.
      fumigatus, allergic sensitisation precedes ABPA development, which occurs in up
      to 10% of CF patients. Progression of lung function deterioration is most
      strikingly pronounced in patients with ABPA. Therefore, sensitisation with A.
      fumigatus should be regularly tested in patients with CF, especially those at
      higher risk. Recombinant allergens constitute an important advance in
      differentiating Aspergillus sensitisation from ABPA itself.

PMID- 20675034
TI  - Role of aeroallergen nasal challenge in asthmatic children.
AB  - BACKGROUND: The majority of allergic asthmatic patients are sensitised to several
      aeroallergens. Discrimination of the clinically relevant allergen is essential
      for the correct use of immunotherapy. OBJECTIVE: To investigate nasal challenge
      and its role in screening clinically relevant allergens in asthmatic children.
      METHODS: Aeroallergen nasal challenge was performed in five different groups of
      patients (asthma; asthma & rhinitis; rhinitis; atopic controls; and non-atopic
      controls). Differences between groups after challenge were evaluated by means of
      spirometry and acoustic rhinometry. RESULTS: Nasal challenge was performed in 125
      patients, 25 per group. The positive nasal response of immediate type was
      recorded in 21 patients with asthma only (P<0.001), 18 with asthma and rhinitis
      (P<0.001), 19 with rhinitis (P<0.001), two atopic control patients and in no
      healthy control patients. However, no differences were observed between the
      asthma group and the groups with rhinitis symptoms. The risk of a positive
      challenge was much higher in the asthma without rhinitis group compared to atopic
      controls (OR 29.57; 95%CI: 5.47-159.97). CONCLUSION: Aeroallergen nasal challenge
      is a safe technique in asthmatic children and could be useful in establishing the
      clinically relevant allergen even in the absence of rhinitis.

PMID- 20675035
TI  - Accuracy of sonographic fetal weight estimation of fetuses with a birth weight of
      1500 g or less.
AB  - OBJECTIVE: To compare 35 commonly used formulae for small and average sized
      fetuses on their accuracy in estimating the birth weight in fetuses of 1500 g or
      less. STUDY DESIGN: For this retrospective study a database search was performed
      for all singleton pregnancies without structural or chromosomal defects and with
      a birth weight of 1500 g or less where the last ultrasound examination was
      performed within seven days before delivery. Percentage error and absolute
      percentage error were calculated based on 35 different weight estimation
      formulae. Multiple regression analysis was used to determine the significant
      contributors to the absolute percentage error. RESULTS: One hundred and ninety
      three cases fulfilled the inclusion criteria. The median birth weight was 990 g.
      The percentage error ranged between -15.2% (underestimation with the Merz I
      formula) and 37.4% (overestimation with the Jordaan formula) and the respective
      standard deviations between 10.5% (Mielke I) and 54.0% (Schillinger),
      respectively. The absolute percentage error was between 8.5% and 37.6%. The most
      accurate weight estimation was achieved with the formula from Mielke (percentage
      error 1.8% and absolute percentage error 8.5%). Multiple regression analysis
      showed that significant contributors to the percentage error of the Mielke
      formula were biparietal diameter (OR=-0.206, p=0.045), occipitofrontal diameter
      (OR=0.765, p<0.0001), abdominal circumference (OR=-2.953, p<0.0001), femur length
      (OR=-0.903, p<0.0001), head to abdomen ratio (OR=-1.080, p<0.0001) and fetal
      weight (OR=2.847, p<0.0001). CONCLUSION: When estimating fetal weight in fetuses
      weighing 1500 g or less, one has to be aware of the great differences in accuracy
      among the formulae.

PMID- 20675036
TI  - Perioperative cesarean delivery morbidity among HIV-infected women under highly
      active antiretroviral treatment: a case-control study.
AB  - OBJECTIVE: To compare post-cesarean complications between HIV-infected women on
      highly active antiretroviral therapy (HAART) and a matched group of non-HIV
      infected women, and to evaluate predisposing risk factors for these complications
      in the HIV group. STUDY DESIGN: We performed a retrospective study of 160 HIV
      infected women and 320 non-infected women who underwent cesarean section in a
      single reference center from 1997 to 2007. All HIV patients were under high
      active antiretroviral therapy (HAART). The women were assessed for a large number
      of major and minor postoperative complications. Selected risk factors for
      perioperative morbidity were analyzed in the HIV-positive group and data were
      analyzed using logistic regression. RESULT(S): Overall postoperative
      complications did not differ significantly between the two groups (26.9% in HIV
      patients vs. 22.8% in controls; OR = 1.24; 95% confidence interval [CI] = 0.8
      1.92). Anemia was the most frequent morbidity observed, affecting 17.5% of HIV
      positive women and 11.8% of controls. Major complications were associated with a
      CD4+ cell count of < 500 cell/ml (OR = 3.28, 95% CI = 1.04-10.31) and prematurity
      < 34 weeks (OR = 9.76, 95% CI = 1.99-47.71). CONCLUSION(S): Post-cesarean
      complications were not significantly increased in HIV-infected women on HAART
      compared to non-HIV-infected women. Prematurity and low CD4+ cell count were risk
      factors for major complications.

PMID- 20675037
TI  - Reducing the rate of preterm birth through a simple antenatal screen-and-treat
      programme: a retrospective cohort study.
AB  - OBJECTIVE: To assess whether a simple screen-and-treat strategy in pregnancy,
      previously tested in a randomised controlled study, also effectively lowers the
      rate of preterm delivery under real-life conditions. STUDY DESIGN: In a
      retrospective cohort study, data were enrolled of 2986 women with singleton
      pregnancies presenting for routine antenatal care between 11 and 24 weeks and
      registering for delivery. Data of 1273 women in the intervention group were
      collected between 1 September 2004 and 31 August 2005. The data of 1713 women in
      the control group had been collected 2 years previously. All women were screened
      for asymptomatic vaginal infection using Gram stain, differentiating between
      bacterial vaginosis, vaginal candidiasis, trichomoniasis, or combinations of any
      of the three. Women with infection received standard treatment and follow-up.
      Prenatal care was the same for women in the intervention and control groups, the
      only difference being the absence of screening and treating for vaginal infection
      in the control group. The primary outcome variable was the rate of preterm
      delivery at less than 37 weeks. Secondary outcome variables were preterm delivery
      at less than 37 weeks combined with birth weights <= 2500 g, <= 2000 g, <= 1500
      g, or <= 1000 g. RESULTS: In the intervention group, the rate of preterm birth
      was significantly lower than in the control group (8.2% vs. 12.1%, p < 0.0001),
      as was the number of preterm infants with birth weights of 2500 g or below. Also,
      a significant difference between groups was found for very preterm deliveries,
      i.e., those occurring before 33 weeks (1.9% vs. 5.4%, p < 0.0001). CONCLUSION:
      Integration of a simple screen-and-treatment programme for common vaginal
      infections into routine antenatal care led to a significant reduction in preterm
      births in a general population of pregnant women.

PMID- 20675038
TI  - Simulating a thermal water quality trading market for education and model
      development.
AB  - Thermal water quality trading is an emerging policy tool that allows thermal
      polluters to comply with effluent restrictions by paying landowners to plant
      shade trees. A simulation game was created to help participants understand the
      structure, dynamics, benefits, and drawbacks of thermal water quality trading
      markets. Simulation participants negotiate to make trades, and their decisions
      are entered into a system dynamics model that simulates tree growth and water
      temperature. A debriefing session allows the participants to discuss outcomes and
      strategies. The exercise has been performed twice and has proven to be a useful
      teaching tool. These simulations provided valuable insight into decision-making
      strategies in thermal water quality trading markets, suggesting decision rules
      that the researchers used for subsequent model development.

PMID- 20675039
TI  - Interaction effects of organic load and cycle time in an AsBr applied to a
      personal care industry wastewater treatment.
AB  - A mechanically stirred anaerobic sequencing batch reactor (ASBR) containing
      granular biomass was applied to the treatment of a wastewater simulating the
      effluent from a personal care industry. The ASBR was operated with cycle lengths
      (t(C)) of 8, 12 and 24 h and applied volumetric organic loads (AVOL) of 0.75,
      0.50 and 0.25 gCOD/L.d, treating 2.0 L liquid medium per cycle. Stirring
      frequency was 150 rpm and the reactor was kept in an isothermal chamber at 30 
      degrees C. Increase in t(C) resulted in efficiency increase at constant AVOL,
      reaching 77% at t(C) of 24 h versus 69% at t(C) of 8 h. However, efficiency
      decreased when AVOL decreased as a function of increasing t(C), due to the lack
      of substrate in the reaction medium. Moreover, replacing part of the wastewater
      by a chemically balanced synthetic one did not yield the expected effect and
      system efficiency dropped.

PMID- 20675040
TI  - Trace metals in river bed sediments: an assessment of their partitioning and
      bioavailability by using multivariate exploratory analysis.
AB  - In this study, river bed sediments were submitted to a BCR sequential extraction,
      together with three bioavailability tests: a weak acid elutriate (HCl), a
      physiologically based extraction test (PBET) and a toxicity characteristic
      leaching procedure (TCLP). The most remarkable features of the BCR procedure
      were: i) Mn and Zn showed the highest proportion of the F1 exchangeable fraction;
      ii) in addition to Fe, Pb and Zn were the metals with the higher percentages in
      the F2 reducible fraction; iii) Fe and Cu were the elements with the highest
      proportion of the F3 oxidizable fraction; iv) the application of Principal
      Component Analysis to the metals in each of the three fractions did not show
      clear associations between metals and sediment components considered as metal
      scavengers, v) considering the sum of the three BCR fractions, the elements
      showed a decreasing availability of: Fe > Pb > Zn > Cu > Mn > Ni > Cr. The single
      extractions followed a decreasing extractability order of: HCl > PBET > TCLP and
      they were far from the extractability deduced from the sum of fractions in the
      BCR extraction.

PMID- 20675042
TI  - Sequestration and in vivo effect of lead on DE2009 microalga, using high
      resolution microscopic techniques.
AB  - Algae are primary producers in a wide variety of natural ecosystems, and these
      microorganisms have been used in bioremediation studies. Nevertheless, very
      little is known about the in vivo effect of heavy metals on individual living
      cells. In this paper, we have applied a method based on confocal laser scanning
      microscopy and lambda scan function (CLSM-lambdascan) to determine the effect of
      lead (Pb), at different concentrations, on the DE2009 microalga. At the same
      time, we have optimized a method based on CLSM and image-analysis software (CLSM
      IA) to determine in vivo biomass of this microorganism. The results obtained by
      lambda scan function indicated that the pigment peak decreases while the
      concentration of metal increases at pH 7. On the other hand at pH 4 there is no
      good correlation between the concentration of metal and the intensity of the
      emission of fluorescence of the pigment. Also, in some cases a displacement of
      the Chl a peak towards 680 nm is produced. Total and individual biomass
      determined by CLSM-IA shows statistically significant differences between
      unpolluted and 10 mM polluted cultures. Complementary studies using electron
      microscopy techniques coupled to energy dispersive X-ray microanalysis (EDX)
      demonstrate that the microalga can sequestrate Pb extra- and intracellularly.

PMID- 20675041
TI  - Preferential induction of G1 arrest in androgen-responsive human prostate cancer
      cells by androgen receptor signaling antagonists DL3 and antiandrogen
      bicalutamide.
AB  - The purpose of this study was to further characterize cell growth-inhibitory
      effects of a recently identified androgen receptor (AR) signaling inhibitor 6
      amino-2-[2-(4-tert-butyl-pnenoxy)-ethylsulfanyl]-1H-pyrimidin-4-one (DL3)(5) and
      antiandrogen bicalutamide (Bic). DL3 was more potent than Bic in induction of G1
      arrest and reduction of G1-related cell cycle protein expression in AR-positive
      LNCaP cells. DL3, but not Bic, moderately inhibited growth of AR-negative PC-3
      cells independent of G1 arrest. The data indicated that DL3 inhibit cell growth
      in both AR-dependent and -independent manners and is potentially a potent
      therapeutic agent for the management of advanced human prostate cancer.

PMID- 20675043
TI  - Emission of polycyclic aromatic hydrocarbons from selected processes in
      steelworks.
AB  - The emission of polycyclic aromatic hydrocarbons from selected processes in
      steelworks in southern Poland was investigated. Size-segregated samples of air
      particulate matter (<0.25, 0.25-0.5, 0.5-1.0, 1.0-2.5 and 2.5-10 MUm) were
      collected at the electric arc furnace and rolling mill. The PAHs were sampled
      with the personal cascade impactor and identified by HPLC with fluorescence
      detector. The obtained results showed that collected PAH contents were
      significantly higher at the electric arc furnace. The highest content of total
      PAHs (93 ng m(-3)) was present in the smallest particles of 0.5 MUm aerodynamic
      diameter or less, indicating that the ultrafine particles have a high
      contribution in the overall PM(2.5) fine fraction. Concentrations of Py, CH, BbF,
      BaP and BghiP came to 76% of total PAHs content in <0.25 MUm fraction. The five-
      and six-ring compounds (BbF, BkF, BaP, DBA, BghiP) with 4-ring chrysene presented
      typical unimodal size distribution with one predominant peak for this particles'
      diameter. Phenanthrene and fluoranthene exhibited highest concentrations on
      coarse particles in the range of 10-2.5 MUm, decreasing with decrease of a
      particle size fraction. Using the toxic equivalent factor (TEF), the mean
      contributions of the carcinogenic potency of BaP to the air samples collected at
      the arc furnace and rolling mill (fraction below 0.25 MUm) were determined to be
      66.3% and 50.3%, respectively.

PMID- 20675044
TI  - The distribution, enrichment and source of potential harmful elements in surface
      sediments of Bohai Bay, North China.
AB  - A geochemical study of Bohai Bay surface sediments was carried out to analyze the
      potential harmful element (PHE: Ge, Mo, In, Sn, Sb, Te, Tl, Bi and V)
      concentrations, transportation and deposition, enrichment factors and sources.
      Germanium, Mo, In, Sn, Sb, Te, Tl, Bi and V concentrations in the surface
      sediments were: 1.43-1.71, 0.52-1.43, 0.04-0.12, 2.77-4.14, 1.14-2.29, 0.027
      0.085, 0.506-0.770, 0.27-0.63 and 70.35-115.90 MUg/g, respectively. The
      distributions of total PHE concentrations, together with sequential extraction
      analyses, showed that the PHEs were mainly due to natural inputs from the
      continental weathering delivered to the bay by rivers and atmospheric
      transportation and deposition. However, high Mo, Sb, Te, Bi and V occurred in non
      residual fractions, suggesting some anthropogenic inputs in addition to the
      natural inputs. Besides sources, the distributions of PHEs were influenced by the
      coupling of physical, chemical and biological processes. Enrichment factor (EF)
      was computed for each site for each element in order to assess the polluting
      elements and the degree of pollution at each site. Results revealed that the EFs
      were generally lower than 1.0, particularly for Ge, Mo, In, Sn, Tl and V;
      however, the EFs were higher (>1.5), particularly for Sb, Te and Bi, revealing
      moderate contamination.

PMID- 20675045
TI  - Cation exchange interaction between antibiotic ciprofloxacin and montmorillonite.
AB  - Exploring the interactions between antibiotics and soils/minerals is of great
      importance in resolving their fate, transport, and elimination in the environment
      due to their frequent detection in wastewater, river water, sewage sludge and
      soils. This study focused on determining the adsorption properties and mechanisms
      of interaction between antibiotic ciprofloxacin and montmorillonite (SAz-1), a
      swelling dioctahedral mineral with Ca(2+) as the main interlayer cation. In
      acidic and neutral aqueous solutions, a stoichiometric exchange between
      ciprofloxacin and interlayer cations yielded an adsorption capacity as high as
      330 mg/g, corresponding to 1.0 mmol/g. When solution pH was above its pK(a2)
      (8.7), adsorption of ciprofloxacin was greatly reduced due to the net repulsion
      between the negatively charged clay surfaces and the ciprofloxacin anion. The
      uptake of ciprofloxacin expanded the basal spacing (d(001)) of montmorillonite
      from 15.04 to 17.23 A near its adsorption capacity, confirming cation exchange
      within the interlayers in addition to surface adsorption. Fourier transform
      infrared results further suggested that the protonated amine group of
      ciprofloxacin in its cationic form was electrostatically attracted to negatively
      charged sites of clay surfaces, and that the carboxylic acid group was hydrogen
      bonded to the basal oxygen atoms of the silicate layers. The results indicate
      that montmorillonite is an effective sorbent to remove ciprofloxacin from water.

PMID- 20675046
TI  - Environmental geochemistry of ancient volcanic ashes.
AB  - Volcanic ashes from the Puna and surrounding Andean areas in northern Argentina
      show that sometimes volcanic ash deposits are very well preserved (up to several
      million years) and can remain a potential hazard for the environment in a similar
      way as current deposits. Eight ashes have been characterized by SEM-EDX and DRX,
      and their potential released geochemical fluxes were examined by using water and
      nitric acid batches, which are analyzed by ICP-OES, ICP-MS and ISE (F). Results
      demonstrate that water batch system is better medium than nitric acid for this
      study. The high and fast reactivity of these ancient ashes is mainly associated
      with their high content in glass. The order of magnitude of released contents of
      implied elements is consistent among the samples, i.e.,
      Al>B>Fe>Zn>F>P>Mn>Ba>Sr>Li>Ti>Rb>Cu>Ni>Sb>Pb>As>Cr>V. Ash-water interaction,
      although infrequent in arid regions such as the Puna Region in northern
      Argentina, introduces rapid changes in the geochemical fluxes of elements and pH
      and may constitute a potential hazard for the environment. In fact, many of these
      elements are included in the drinking water guidelines due to their potential
      toxicity and may constitute potential hazards for the environment and human
      health.

PMID- 20675047
TI  - Behaviors and mechanism of acid dyes sorption onto diethylenetriamine-modified
      native and enzymatic hydrolysis starch.
AB  - In this paper, different starches were modified by diethylenetriamine. The native
      starch reacted with diethylenetriamine giving CAS, whereas the enzymatic
      hydrolysis starch was modified by diethylenetriamine producing CAES. Adsorption
      capacities of CAES for four acid dyes, namely, Acid orange 7 (AO7), Acid orange
      10 (AO10), Acid green 25 (AG25) and Acid red 18 (AR18) have been determined to be
      2.521, 1.242, 1.798 and 1.570 mmol g(-1), respectively. In all cases, CAES has
      exhibited higher sorption ability than CAS, and the increment for these dyes took
      the sequence of AO7 (0.944 mmol g(-1))>AO10 (0.592 mmol g(-1))>AR18 (0.411 mmol
      g(-1))>AG25 (0.047 mmol g(-1)). Sorption kinetics and isotherms analysis showed
      that these sorption processes were better fitted to pseudo-second-order equation
      and Langmuir equation. Chemical sorption mechanisms were confirmed by studying
      the effects of pH, ionic strength and hydrogen bonding. Thermodynamic parameters
      of these dyes onto CAES and CAS were also observed and it indicated that these
      sorption processes were exothermic and spontaneous in nature.

PMID- 20675048
TI  - Cadmium biosorption by ozonized activated sludge: the role of bacterial flocs
      surface properties and mixed liquor composition.
AB  - Cadmium uptake by activated sludge was studied following modifications of sludge
      composition and surface properties induced by ozone treatment. Ozone leads to the
      solubilization of sludge compounds as well as their mineralization, especially
      humic like substances. Small particles were formed following floc disintegration,
      leading to a decrease of average floc size. The study of surface properties
      underlined the mineralization as the number of surface binding sites decreased
      with the increase of ozone dose. Depending on ozone dose, cadmium uptake by
      activated sludge flocs was either increased or decreased. Different mechanisms
      were involved: below 10 mg O(3)/g TS, the increase of floc specific surface area
      following floc size decrease as well as the release of phosphate ions yielded an
      increase by 75% of cadmium uptake, due to the better availability of biosorption
      sites and the increase of precipitation. Inversely, at higher ozone doses, the
      number of biosorption sites decreased due to oxidation by ozone. Moreover,
      dissolved organic matter concentration increased and provided ligands for metal
      complexation. Cadmium uptake was therefore limited for ozone doses ranging from
      10 to 16.8 mg O(3)/g TS.

PMID- 20675049
TI  - Copper extraction from ammoniacal medium in a pulsed sieve-plate column with LIX
      84-I.
AB  - This article reports on a study of copper removal from ammoniacal aqueous
      solution (1.0 kg m(-3) Cu, pH 9.5) by liquid-liquid extraction using a pulsed
      sieve-plate column. The extractant tested was the hydroxyoxime LIX 84-I (2
      hydroxy-5-nonylacetophenone oxime) in the aliphatic diluent Shellsol D-70. The
      results of the pilot plant experiments demonstrated the feasibility of operating
      the extraction process in this type of column, with efficiencies of copper
      removal in the range of 90.5-99.5%. Several effects on the column performance
      were examined, namely the aqueous and organic flow rates and the pulse velocity.
      The axial dispersion model was applied to simulate the concentration profiles,
      which reasonably predicted the experimental data. The overall mass transfer
      coefficient was evaluated from the experimental data and was found to be between
      9*10(-6) and 1.2*10(-5) m s(-1). These data were compared with the ones obtained
      from the resistances in series model, which indicated that the resistance due to
      chemical reaction was 84-91% of the overall resistance to mass transfer. The
      extraction using a hollow fiber contactor was also carried out to compare the
      membrane process performance with the one of conventional process.

PMID- 20675050
TI  - The efficacy and mechanisms of fungal suppression of freshwater harmful algal
      bloom species.
AB  - Microorganisms have attracted worldwide attention as possible agents for
      inhibiting water blooms. Algae are usually indirectly inhibited and degraded by
      secretion from microorganisms. In this study, algal cultures Microcystis
      aeruginosa (Ma) FACH-918, Microcystis flos-aquae (Mf) FACH-1028, Oocystis borgei
      (Ob) FACH-1108, and M. aeruginosa PCC 7806 were co-cultured with the fungus
      strain Trichaptum abietinum 1302BG. All algal cells were destroyed within 48
      hours (h) of co-incubation. Scanning electron microscope and transmission
      electron microscope observation revealed that the fungal strain had preying
      ability on the algal cells. The mechanism may be that the algal cells were
      encased with a mucous membrane secreted by the fungal mycelia, and finally
      degraded by the fungus directly.

PMID- 20675051
TI  - Catalytic ozonation of fenofibric acid over alumina-supported manganese oxide.
AB  - The catalytic ozonation of fenofibric acid was studied using activated alumina
      and alumina-supported manganese oxide in a semicontinuous reactor. The rate
      constants at 20 degrees C for the non-catalytic reaction of fenofibric acid with
      ozone and hydroxyl radicals were 3.43+/-0.20 M(-1) s(-1) and (6.55+/-0.33)*10(9)
      M(-1) s(-1), respectively. The kinetic constant for the catalytic reaction
      between fenofibric acid and hydroxyl radicals did not differ significantly from
      that of homogeneous ozonation, either using Al(2)O(3) or MnO(x)/Al(2)O(3). The
      results showed a considerable increase in the generation of hydroxyl radicals due
      to the use of catalysts even in the case of catalytic runs performed using a real
      wastewater matrix. Both catalysts promoted the decomposition of ozone in
      homogeneous phase, but the higher production of hydroxyl radicals corresponded to
      the catalyst with more activity in terms of ozone decomposition. We did not find
      evidence of the catalysts having any effect on rate constants, which suggests
      that the reaction may not involve the adsorption of organics on catalyst surface.

PMID- 20675052
TI  - Synthesis of novel tripodal-benzimidazole from 2,4,6-tris(p-formylphenoxy)-1,3,5
      triazine: structural, electrochemical and antimicrobial studies.
AB  - Four new tripodal-benzimidazole derivatives were synthesized by Schiff base
      reaction between 2,4,6-tris(p-formylphenoxy)-1,3,5-triazine (TRIPOD) and
      different diamine derivatives. The structures of the obtained compounds were
      identified by FT-IR, (1)H NMR, (13)C NMR and UV-vis spectral data, thermal
      analysis and elemental analysis. Electrochemical behaviors of the compounds were
      studied by cyclic voltammetry in DMF including 0.1 M [NBu(4)] [PF(6)]. The
      voltammograms showed peaks having similar characteristics except tripodal
      benzimidazole including -NO(2) derivative. In addition, their antimicrobial
      activities were evaluated by using the standard disk diffusion method in
      dimethylformamide media. The activities were determined against 4 bacteria
      cultures by comparing to those of gentamycin.

PMID- 20675054
TI  - Above-level mechanical hyperalgesia in rats develops after incomplete spinal cord
      injury but not after cord transection, and is reversed by amitriptyline, morphine
      and gabapentin.
AB  - Spinal cord injury (SCI) is a major cause of persistent neuropathic pain of
      central origin. Recent evidence suggests neuropathic pain in clinically complete
      SCI patients correlates with limited sensory function below the lesion (sensory
      discomplete). On this basis we examined if the onset of mechanical hyperalgesia
      was different in rodents after a severe incomplete clip-compression SCI versus a
      complete spinal cord transection at thoracic segment T13. Above-level withdrawal
      behaviors evoked by forepaw stimulation provided evidence of mechanical
      hyperalgesia after incomplete but not complete SCI, whereas below-level responses
      evoked by hindpaw stimulation revealed hypersensitivity after both injuries. The
      latency of the above-level response was 4-5 wks but was longer after a moderate
      clip-compression injury. Mechanical hyperalgesia was fully reversed by three
      analgesic drugs used in treating neuropathic SCI pain, but their duration of
      action differed significantly, showing a rank order of amitriptyline (24-48
      h)?morphine (6 h)>gabapentin (2 h). Evidence of central sensitization in cervical
      spinal cord segments that receive sensory projections from the forelimbs was
      provided by immunohistochemistry for Zif268, a functional marker of
      neuroplasticity. Zif268-immunoreactive neurons in laminae I/II increased in
      response to repetitive noxious forepaw stimulation in the incomplete SCI group,
      and this response was reduced in the complete transection and sham-operated
      groups. These data are consistent with the hypothesis that neuropathic pain of
      cord origin is more likely to develop after SCI when there is an incomplete loss
      of axons traversing the lesion.

PMID- 20675053
TI  - Role of peripheral endothelin receptors in an animal model of complex regional
      pain syndrome type 1 (CRPS-I).
AB  - Chronic post-ischemic pain (CPIP) is an animal model of CRPS-I developed using a
      3-h ischemia-reperfusion injury of the rodent hind paw. The contribution of local
      endothelin to nociception has been evaluated in CPIP mice by measuring sustained
      nociceptive behaviors (SNBs) following intraplantar injection of endothelin-1 or 
      2 (ET-1, ET-2). The effects of local BQ-123 (ETA-R antagonist), BQ-788 (ETB-R
      antagonist), IRL-1620 (ETB-R agonist) and naloxone (opioid antagonist) were
      assessed on ET-induced SNBs and/or mechanical and cold allodynia in CPIP mice.
      ETA-R and ETB-R expression was assessed using immunohistochemistry and Western
      blot analysis. Compared to shams, CPIP mice exhibited hypersensitivity to local
      ET-1 and ET-2. BQ-123 reduced ET-1- and ET-2-induced SNBs in both sham and CPIP
      animals, but not mechanical or cold allodynia. BQ-788 enhanced ET-1- and ET-2
      induced SNBs in both sham and CPIP mice, and cold allodynia in CPIP mice. IRL
      1620 displayed a non-opioid anti-nociceptive effect on ET-1- and ET-2-induced
      SNBs and mechanical allodynia in CPIP mice. The distribution of ETA-R and ETB-R
      was similar in plantar skin of sham and CPIP mice, but both receptors were over
      expressed in plantar muscles of CPIP mice. This study shows that ETA-R and ETB-R
      have differing roles in nociception for sham and CPIP mice. CPIP mice exhibit
      more local endothelin-induced SNBs, develop a novel local ETB-R agonist-induced
      (non-opioid) analgesia, and exhibit over-expression of both receptors in plantar
      muscles, but not skin. The effectiveness of local ETB-R agonists as anti
      allodynic treatments in CPIP mice holds promise for novel therapies in CRPS-I
      patients.

PMID- 20675055
TI  - Shortened strongyle-type egg reappearance periods in naturally infected horses
      treated with moxidectin and failure of a larvicidal dose of fenbendazole to
      reduce fecal egg counts.
AB  - Deworming horses with anthelmintics that have activity against encysted small
      strongyle larvae (L(3) and L(4)) is a common practice in parasite control
      programs. The two drugs currently available for this use are moxidectin (MOX)
      administered in a single dose of 0.4 mg/kg and fenbendazole (FBZ) given at the
      larvicidal dose (10mg/kg for 5 days). Here, we report the efficacy of MOX and the
      larvicidal dose of FBZ for reducing counts of strongyle-type eggs per gram of
      feces in naturally infected horses. Fecal egg counts (FECs) of 15 yearlings were
      observed following deworming. On day 0, 6 of the 15 yearlings were administered a
      larvicidal dose of FBZ; 14 days later, all 15 yearlings received MOX at a single
      dose of 0.4 mg/kg. Feces were collected on day 0 for pre-treatment egg counts.
      Feces were collected at weekly intervals thereafter during FEC observation
      periods. FECs of FBZ-treated horses were compared at day 0 and 14 days post
      treatment. The difference in means pre- and post-treatment with FBZ was not
      statistically significant (p=0.65). On days 0 and 42 of the MOX treatment
      observation period the mean FEC of the yearlings that had not received the FBZ
      treatment did not differ significantly from that of the FBZ-treated yearlings.
      MOX was effective in reducing fecal egg counts to 0 EPG for 21 days. At day 35
      all but 2 of the yearlings had some eggs present (range=4-361 EPG) and at day 42
      all but 1 yearling had eggs present (range=3-432 EPG). At day 42 the group mean
      FEC reduction had fallen from 100% to 67%. Results of this study do not support
      the use of the larvicidal dose of FBZ for small strongyle control. Larger field
      studies will be needed to investigate whether egg reappearance periods are
      shortening for MOX-treated horses.

PMID- 20675056
TI  - Malignant pheochromocytomas and paragangliomas - the importance of a
      multidisciplinary approach.
AB  - Approximately 10% of the pheochromocytomas and 20% of the paragangliomas are
      malignant with poor survival. As the biological behaviour of these tumours cannot
      be predicted with certainty from pathology the diagnosis of malignancy is
      difficult. Genetic testing is gaining impact as mutations in the tumour
      suppressor gene Von Hippel-Lindau and the mitochondrial succinate dehydrogenase
      enzyme complex subunit B (SDHB) are associated with malignancy. Excess release of
      catecholamines is characteristic for pheochromocytomas. High levels of
      chromogranin A, that is co-stored and co-secreted with catecholamines, may
      indicate tumour mass and malignancy and can be used to monitor response and
      relapse. The secretory and non-secretory tumours can be visualised with
      functional (specific and non-specific) imaging as SPECT and PET using 123I-MIBG,
      somatostatin analogues, 18F-DOPA, and 18F-FDG. These modalities are recommended
      in patients with extra-adrenal and suspected metastatic/malignant disease, in
      case of distorted post-operative anatomy, and when suspected recurrence. The
      sensitivities of 123I-MIBG scintigraphy or 18F-DOPA PET are relatively low in
      SDHB mutated tumours, but high using 18F-FDG. Specific PET imaging with
      somatostatin analogues generally has high sensitivity in malignant disease. There
      are no curative therapeutic options for malignant, metastatic
      pheochromocytomas/paragangliomas, wherefore consolidation of quality of life is
      essential. Adjuvant radionuclide treatment with beta-emitting isotopes coupled to
      MIBG or somatostatin analogues have shown response in approximately 30%.
      Chemotherapy is restricted to patients not accessible for surgery and resistant
      to radionuclide therapy. Novel targeted therapies, which mainly through a
      cytostatic effect interfere with specific targeted molecules needed for
      carcinogenesis and tumour growth show encouraging results.

PMID- 20675058
TI  - Osteoporosis as a potential contributor to the bone metastases.
AB  - Bone metastasis is a serious complication of patients with tumor, and most
      primary tumors can metastasize to bone. And the main threat and the reason for
      most cancer deaths are not the primary neoplasias, but secondary tumors, the
      metastases. To minimize the morbidity and economic expenditure associated with
      bone metastases, it is important to decrease the etiological factors of bone
      metastasis. Although current evidence suggested that the therapies to the
      underlying malignancy bone metastasis might result in bone loss leading to
      osteoporosis, no studies have shown direct evidence the successful seeding of
      bone metastases of cancer cells is the part played by osteoporosis. In the state
      of osteoporosis, for the enhancement of the osteolysis, the increased
      inflammatory factors could make blood vessels leakier, resulting in the easier
      hematogenous metastasis to bone and bone marrow. Moreover, leptin, which was
      positive correlation with osteoporosis, has been showed to exert angiogenic
      effects and could regulate VEGF expression, promoting the proliferation of the
      cancer blood vessel. In addition, the increased growth factors in osteoporosis
      could enrich the local microenvironment, promoting the growth of the metastasis
      mass. Given the above background, we hypothesize that osteoporosis may be a
      potential contributor to the bone metastases.

PMID- 20675059
TI  - Can time production predict cognitive decline?
AB  - Time production may predict age-related losses in verbal and visuospatial
      functions in a fashion similar to reaction time measurements. In a preliminary
      investigation, young subjects outperformed older ones in the Rey auditory-verbal
      learning test and Raven's Standard Progressive Matrices, but not in time
      productions of 3-10s. Nevertheless, time production of a brief interval was
      correlated with verbal learning scores. These results may be due to age-related
      changes in prefrontal cortex.

PMID- 20675057
TI  - Progesterone improves cognitive performance and attenuates smoking urges in
      abstinent smokers.
AB  - BACKGROUND: Progesterone, a steroid hormone, has been implicated in many CNS
      functions including reward, cognition, and neuroprotection. The goal of this
      study was to examine the dose-dependent effects of progesterone on cognitive
      performance, smoking urges, and smoking behavior in smokers. METHODS: Thirty
      female and thirty-four male smokers participated in a double-blind, placebo
      controlled study. Female smokers were in the early follicular phase of their
      menstrual cycle during study participation. Smokers were randomly assigned to
      either 200 or 400mg/day of progesterone or placebo, given in two separate doses,
      during clinic visit. The first 3 days of the treatment period, smokers abstained
      from smoking, which was verified with breath CO levels. Smokers attended an
      experimental session on day 4 where the number of cigarettes smoked were recorded
      starting 2h after the medication treatment. RESULTS: Progesterone treatment,
      200mg/day, significantly improved cognitive performance in the Stroop and the
      Digit Symbol Substitution Test. Progesterone at 400mg/day was associated with
      reduced urges for smoking but did not change ad lib smoking behavior.
      CONCLUSIONS: These findings suggest a potential therapeutic value of progesterone
      for smoking cessation.

PMID- 20675060
TI  - The porcine tribbles homolog 3 (TRIB3) gene: Identification of a missense
      mutation and association analysis with meat quality and production traits in
      Italian heavy pigs.
AB  - TRIB3 plays an important role in energy metabolism. This work aimed to study the
      porcine tribbles homolog 3 (TRIB3) gene and to evaluate its association with meat
      quality and carcass traits in pigs. By sequencing a portion of the porcine TRIB3
      gene two single nucleotide polymorphisms (SNPs) in the first coding exon (one
      synonymous SNP: c.132 T>C; and one missense mutation: c.146C>T, p.P49L) were
      identified. The two polymorphisms were in complete linkage disequilibrium. In
      silico analysis of the p.P49L mutation suggested that it could have functional
      effects. Association studies in four groups of pigs (651 animals in total)
      indicated that this gene marker was associated with back fat thickness in Italian
      Large White and Italian Duroc pigs in two different experimental designs (P<0.1
      and P<0.05). This polymorphism tended to be associated with lactate content of
      the semimembranosus muscle (P<0.1). Among several other tissues, TRIB3 is
      expressed in fat and skeletal muscle.

PMID- 20675061
TI  - Semiquantitative detection of male pork tissue in meat and meat products by PCR.
AB  - Consumer awareness has increased concerning castration of piglets without
      analgesia or anaesthesia. On the other hand the occurrence of boar taint is not
      tolerated by consumers. Currently no reliable methods exist for the on-line
      detection of boar taint in the slaughterhouse or for genetic sexing of pigs.
      Therefore, as an alternative the detection of male pork meat was sought. Based on
      detection of a length polymorphism of the sex chromosomal amelogenin gene a
      reliable, specific and highly sensitive PCR method for qualitative and semi
      quantitative determination of male pork tissue in meat and meat products was
      determined. A set of 25 male and 25 female meat samples could be correctly
      identified and mixtures with as little as 0.1% male meat content could be
      detected. Therefore the method can be used for production and control of specific
      meat products containing low amounts of male pork meat and thus avoiding boar
      taint.

PMID- 20675062
TI  - Intramuscular fatty acid composition of "Galician Mountain" foals breed. Effect
      of sex, slaughtered age and livestock production system.
AB  - The effects of sex, slaughtered age (9 vs. 12 months) and livestock production
      system (freedom extensive system vs. semi extensive system) of "Galician
      Mountain" foals breed on the fatty acid composition were studied. The sex and
      slaughtered age of the animals had no statistical significance in the
      intramuscular fatty acids. Furthermore, the livestock production system showed
      differences in the fatty acid profiles from the Longissimus dorsi. The feeding
      system showed significant differences in PUFA content (P<0.001) higher in freedom
      extensive production system that semi extensive system, whereas MUFA content was
      significantly (P<0.001) higher in semi extensive system. This major PUFA content
      in freedom extensive production showed a significant (r=0.70, P<0.01) correlation
      with C18:3n-3 content and can be attributed to their eaten only pasture until
      slaughtered. The higher MUFA contents (P<0.001) observed for semi extensive
      production system foals were very significant (r=0.98, p<0.01) correlated with
      C18:1cis-9 content and less significant (r=0.81, P<0.01) correlated with C16:1cis
      9 content. In addition, the data reinforced the evidence that foals from
      extensive production system on wood pasture have a higher nutritional quality
      (mainly due to the higher levels of n-3 PUFA) when compared to concentrate-fed
      foals, as a result of the beneficial effects of grass on meat fatty acid
      profiles.

PMID- 20675063
TI  - Comparison of liver tumor motion with and without abdominal compression using
      cine-magnetic resonance imaging.
AB  - PURPOSE: Abdominal compression (AC) can be used to reduce respiratory liver
      motion in patients undergoing liver stereotactic body radiotherapy. The purpose
      of the present study was to measure the changes in three-dimensional liver tumor
      motion with and without compression using cine-magnetic resonance imaging.
      PATIENTS AND METHODS: A total of 60 patients treated as a part of an
      institutional research ethics board-approved liver stereotactic body radiotherapy
      protocol underwent cine T2-weighted magnetic resonance imaging through the tumor
      centroid in the coronal and sagittal planes. A total of 240 cine-magnetic
      resonance imaging sequences acquired at one to three images each second for 30-60
      s were evaluated using an in-house-developed template matching tool (based on the
      coefficient correlation) to measure the magnitude of the tumor motion. The
      average tumor edge displacements were used to determine the magnitude of changes
      in the caudal-cranial (CC) and anteroposterior (AP) directions, with and without
      AC. RESULTS: The mean tumor motion without AC of 11.7 mm (range, 4.8-23.3) in the
      CC direction was reduced to 9.4 mm (range, 1.6-23.4) with AC. The tumor motion
      was reduced in both directions (CC and AP) in 52% of the patients and in a single
      direction (CC or AP) in 90% of the patients. The mean decrease in tumor motion
      with AC was 2.3 and 0.6 mm in the CC and AP direction, respectively. Increased
      motion occurred in one or more directions in 28% of patients. Clinically
      significant (>3 mm) decreases were observed in 40% and increases in <2% of
      patients in the CC direction. CONCLUSION: AC can significantly reduce three
      dimensional liver tumor motion in most patients, although the magnitude of the
      reduction was smaller than previously reported.

PMID- 20675064
TI  - Accelerated partial breast irradiation with interstitial implants: risk factors
      associated with increased local recurrence.
AB  - PURPOSE: To analyze patient, disease, and treatment-related factors regarding
      their impact on local control after interstitial multicatheter accelerated
      partial breast irradiation (APBI). METHODS AND MATERIALS: Between November 2000
      and April 2005, 274 patients with early breast cancer were recruited for the
      German-Austrian APBI Phase II trial (ClinicalTrials.gov identifier: NCT00392184).
      In all, 64% (175/274) of the patients received pulsed-dose-rate (PDR)
      brachytherapy and 36% (99/274) received high-dose-rate (HDR) brachytherapy.
      Prescribed reference dose for HDR brachytherapy was 32 Gy in eight fractions of 4
      Gy, twice daily. Prescribed reference dose in PDR brachytherapy was 49.8 Gy in 83
      consecutive fractions of 0.6 Gy each hour. Total treatment time was 3 to 4 days.
      RESULTS: The median follow-up time was 64 months (range, 9-110). The actuarial 5
      year local recurrence free survival rate (5-year LRFS) was 97.7%. Comparing
      patients with an age <50 years (49/274) vs. >=50 years (225/274), the 5-year LRFS
      resulted in 92.5% and 98.9% (exact p = 0.030; 99% confidence interval, 0.029
      0.032), respectively. Antihormonal treatment (AHT) was not applied in 9% (24/274)
      of the study population. The 5-year LRFS was 99% and 84.9% (exact p = 0.0087; 99%
      confidence interval, 0.0079-0.0094) in favor of the patients who received AHT.
      Lobular histology (45/274) was not associated with worse local control compared
      with all other histologies (229/274). The 5-year LRFS rates were 97.6% and 97.8%,
      respectively. CONCLUSIONS: Local control at 5 years is excellent and comparable
      to therapeutic successes reported from corresponding whole-breast irradiation
      trials. Our data indicate that patients <50 years of age ought to be excluded
      from APBI protocols, and that patients with hormone-sensitive breast cancer
      should definitely receive adjuvant AHT when interstitial multicatheter APBI is
      performed. Lobular histology need not be an exclusion criterion for future APBI
      trials.

PMID- 20675065
TI  - Usefulness of interim FDG-PET after induction chemotherapy in patients with
      locally advanced squamous cell carcinoma of the head and neck receiving
      sequential induction chemotherapy followed by concurrent chemoradiotherapy.
AB  - PURPOSE: Induction chemotherapy (ICT) has been used to select patients for organ
      preservation and determine subsequent treatments in patients with locally
      advanced squamous cell carcinoma of the head and neck (LASCCHN). Still, the
      clinical outcomes of LASCCHN patients who showed response to ICT are
      heterogeneous. We evaluated the efficacy of interim 18-fluoro-2-deoxy-glucose
      positron emission tomography (FDG-PET) after ICT in this specific subgroup of
      LASCCHN patients who achieved partial response (PR) after ICT to predict clinical
      outcomes after concurrent chemoradiotherapy (CCRT). METHODS AND MATERIALS: Twenty
      one patients with LASCCHN who showed PR to ICT by Response Evaluation Criteria In
      Solid Tumors before definitive CCRT were chosen in this retrospective analysis.
      FDG-PET was performed before and 2-4 weeks after ICT to assess the extent of
      disease at baseline and the metabolic response to ICT, respectively. We examined
      the correlation of the metabolic response by the percentage decrease of maximum
      standardized uptake value (SUVmax) on the primary tumor or lymph node after ICT
      or a specific threshold of SUVmax on interim FDG-PET with clinical outcomes
      including complete response (CR) rate to CCRT, progression-free survival (PFS),
      and overall survival (OS). RESULTS: A SUVmax of 4.8 on interim FDG-PET could
      predict clinical CR after CCRT (100% vs. 20%, p=0.001), PFS (median, not reached
      vs. 8.5 mo, p<0.001), and OS (median, not reached vs. 12.0 months, p=0.001) with
      a median follow-up of 20.3 months in surviving patients. A 65% decrease in SUVmax
      after ICT from baseline also could predict clinical CR after CCRT (100% vs.
      33.3%, p=0.003), PFS (median, not reached vs. 8.9 months, p<0.001) and OS
      (median, not reached vs. 24.4 months, p=0.001) of the patients. CONCLUSION: These
      data suggest that interim FDG-PET after ICT might be a useful determinant to
      predict clinical outcomes in patients with LASCCHN receiving sequential ICT
      followed by CCRT.

PMID- 20675066
TI  - Local tumor control, visual acuity, and survival after hypofractionated
      stereotactic photon radiotherapy of choroidal melanoma in 212 patients treated
      between 1997 and 2007.
AB  - PURPOSE: To evaluate long-term local tumor control, visual acuity, and survival
      after hypofractionated linear accelerator-based stereotactic photon radiotherapy
      in patients with choroidal melanoma. METHODS AND MATERIALS: Between 1997 and
      2007, 212 patients with choroidal melanoma unsuitable for ruthenium-106
      brachytherapy or local resection were treated stereotactically at a linear
      accelerator with 6-MV photon beams at the Medical University of Vienna in five
      fractions over 7 days. Twenty-four patients received a total dose of 70 Gy (five
      fractions of 14 Gy), 158 a total dose of 60 Gy (five fractions of 12 Gy) and 30
      patients a total dose of 50 Gy (five fractions of 10 Gy) applied on the 80%
      isodose. Ophthalmologic examinations were performed at baseline and every 3
      months in the first 2 years, every 6 months until 5 years, and once a year
      thereafter until 10 years after radiotherapy. Assessment of visual acuity,
      routine ophthalmologic examinations, and measurement of tumor base dimension and
      height using standardized A-scan and B-scan echography were done at each visit.
      Funduscopy and fluorescein angiography were done when necessary to document tumor
      response. RESULTS: Median tumor height and volume decreased from 4.8 mm and 270.7
      mm3 at baseline to 2.6 mm and 86.6 mm3 at the last individual follow-up,
      respectively (p<0.001, p<0.001). Median visual acuity decreased from 0.55 at
      baseline to hand motion at the last individual follow-up (p<0.001). Local tumor
      control was 95.9% after 5 years and 92.6% after 10 years. Thirty-two patients
      developed metastatic disease, and 22 of these patients died during the follow-up
      period. CONCLUSION: Hypofractionated stereotactic photon radiotherapy with 70 to
      50 Gy delivered in five fractions in 7 days is sufficient to achieve excellent
      local tumor control in patients with malignant melanoma of the choroid. Disease
      outcome and vision are comparable to those achieved with proton beam
      radiotherapy. Decreasing the total dose below 60 Gy seems to be possible.

PMID- 20675067
TI  - Proton radiotherapy: the biological effect of treating alternating subsets of
      fields for different treatment fractions.
AB  - PURPOSE: Common practice in proton radiotherapy is to deliver a subset of all
      fields in the treatment plan on any given treatment day. We investigate using
      biological modeling if the resulting variation in daily dose to normal tissues
      has a relevant detrimental biological effect. METHODS AND MATERIALS: For four
      patient groups, the cumulative normalized total dose (NTD) was determined for
      normal tissues (OARs) of each patient using the clinically delivered
      fractionation schedule (FS(clin)), and for hypothetical fractionation schedules
      delivering all fields every day (FS(all)) or only a single field each day
      (FS(single)). Cumulative three-dimensional NTD distributions were summarized
      using the generalized equivalent uniform dose (gEUD) model. RESULTS: For the
      skull base/cervical spine chordoma group, the largest effect is a 4-Gy increase
      in gEUD of the chiasm when treating only a subset of fields on any day. For lung
      cancer and pancreatic cancer patients, the variation in the gEUD of normal
      tissues is <0.2 Gy. For the prostate group, FS(clin) increases the gEUD of the
      femoral heads by 9 Gy compared with FS(all). Use of FS(single) resulted in the
      highest NTD to normal tissues for any patient. FS(all) resulted in an integral
      NTD to the patient that is on average 5% lower than FS(clin) and 10% lower than
      FS(single). CONCLUSION: The effects of field set of the day treatment delivery
      depend on the tumor site and number of fields treated each day. Modeling these
      effects may be important for accurate risk assessment.

PMID- 20675068
TI  - Effectiveness of radiotherapy for elderly patients with glioblastoma.
AB  - PURPOSE: Radiotherapy plays a central role in the definitive treatment of
      glioblastoma. However, the optimal management of elderly patients with
      glioblastoma remains controversial, as the relative benefit in this patient
      population is unclear. To better understand the role that radiation plays in the
      treatment of glioblastoma in the elderly, we analyzed factors influencing patient
      survival using a large population-based registry. METHODS AND MATERIALS: A total
      of 2,836 patients more than 70 years of age diagnosed with glioblastoma between
      1993 and 2005 were identified from the Surveillance, Epidemiology, and End
      Results (SEER) registry. Demographic and clinical variables used in the analysis
      included gender, ethnicity, tumor size, age at diagnosis, surgery, and
      radiotherapy. Cancer-specific survival and overall survival were evaluated using
      the Kaplan-Meier method. Univariate and multivariate analysis were performed
      using Cox regression. RESULTS: Radiotherapy was administered in 64% of these
      patients, and surgery was performed in 68%. Among 2,836 patients, 46% received
      surgery and radiotherapy, 22% underwent surgery only, 18% underwent radiotherapy
      only, and 14% did not undergo either treatment. The median survival for patients
      who underwent surgery and radiotherapy was 8 months. The median survival for
      patients who underwent radiotherapy only was 4 months, and for patients who
      underwent surgery only was 3 months. Those who received neither surgery nor
      radiotherapy had a median survival of 2 months (p<0.001). Multivariate analysis
      showed that radiotherapy significantly improved cancer-specific survival (hazard
      ratio [HR], 0.43, 95% confidence interval [CI] 0.38-0.49) after adjusting for
      surgery, tumor size, gender, ethnicity, and age at diagnosis. Other factors
      associated with Cancer-specific survival included surgery, tumor size, age at
      diagnosis, and ethnicity. Analysis using overall survival as the endpoint yielded
      very similar results. CONCLUSIONS: Elderly patients with glioblastoma who
      underwent radiotherapy had improved cancer-specific survival and overall survival
      compared to patients who did not receive radiotherapy.

PMID- 20675069
TI  - Prediction of response to preoperative chemoradiotherapy in rectal cancer by
      multiplex kinase activity profiling.
AB  - PURPOSE: Tumor response of rectal cancer to preoperative chemoradiotherapy (CRT)
      varies considerably. In experimental tumor models and clinical radiotherapy,
      activity of particular subsets of kinase signaling pathways seems to predict
      radiation response. This study aimed to determine whether tumor kinase activity
      profiles might predict tumor response to preoperative CRT in locally advanced
      rectal cancer (LARC). METHODS AND MATERIALS: Sixty-seven LARC patients were
      treated with a CRT regimen consisting of radiotherapy, fluorouracil, and, where
      possible, oxaliplatin. Pretreatment tumor biopsy specimens were analyzed using
      microarrays with kinase substrates, and the resulting substrate phosphorylation
      patterns were correlated with tumor response to preoperative treatment as
      assessed by histomorphologic tumor regression grade (TRG). A predictive model for
      TRG scores from phosphosubstrate signatures was obtained by partial-least-squares
      discriminant analysis. Prediction performance was evaluated by leave-one-out
      cross-validation and use of an independent test set. RESULTS: In the patient
      population, 73% and 15% were scored as good responders (TRG 1-2) or intermediate
      responders (TRG 3), whereas 12% were assessed as poor responders (TRG 4-5). In a
      subset of 7 poor responders and 12 good responders, treatment outcome was
      correctly predicted for 95%. Application of the prediction model on the remaining
      patient samples resulted in correct prediction for 85%. Phosphosubstrate
      signatures generated by poor-responding tumors indicated high kinase activity,
      which was inhibited by the kinase inhibitor sunitinib, and several discriminating
      phosphosubstrates represented proteins derived from signaling pathways implicated
      in radioresistance. CONCLUSIONS: Multiplex kinase activity profiling may identify
      functional biomarkers predictive of tumor response to preoperative CRT in LARC.

PMID- 20675070
TI  - High retention and safety of percutaneously implanted endovascular embolization
      coils as fiducial markers for image-guided stereotactic ablative radiotherapy of
      pulmonary tumors.
AB  - PURPOSE: To compare the retention rates of two types of implanted fiducial
      markers for stereotactic ablative radiotherapy (SABR) of pulmonary tumors, smooth
      cylindrical gold "seed" markers ("seeds") and platinum endovascular embolization
      coils ("coils"), and to compare the complication rates associated with the
      respective implantation procedures. METHODS AND MATERIALS: We retrospectively
      analyzed the retention of percutaneously implanted markers in 54 consecutive
      patients between January 2004 and June 2009. A total of 270 markers (129 seeds,
      141 coils) were implanted in or around 60 pulmonary tumors over 59 procedures.
      Markers were implanted using a percutaneous approach under computed tomography
      (CT) guidance. Postimplantation and follow-up imaging studies were analyzed to
      score marker retention relative to the number of markers implanted. Markers
      remaining near the tumor were scored as retained. Markers in a distant location
      (e.g., pleural space) were scored as lost. CT imaging artifacts near markers were
      quantified on radiation therapy planning scans. RESULTS: Immediately after
      implantation, 140 of 141 coils (99.3%) were retained, compared to 110 of 129
      seeds (85.3%); the difference was highly significant (p<0.0001). Of the total
      number of lost markers, 45% were reported lost during implantation, but 55% were
      lost immediately afterwards. No additional markers were lost on longer-term
      follow-up. Implanted lesions were peripherally located for both seeds (mean
      distance, 0.33 cm from pleural surface) and coils (0.34 cm) (p=0.96). Incidences
      of all pneumothorax (including asymptomatic) and pneumothorax requiring chest
      tube placement were lower in implantation of coils (23% and 3%, respectively) vs.
      seeds (54% and 29%, respectively; p=0.02 and 0.01). The degree of CT artifact was
      similar between marker types. CONCLUSIONS: Retention of CT-guided percutaneously
      implanted coils is significantly better than that of seed markers. Furthermore,
      implanting coils is at least as safe as implanting seeds. Using coils should
      permit implantation of fewer markers and require fewer repeat implantation
      procedures owing to lost markers.

PMID- 20675071
TI  - Treatment outcomes of locally advanced oropharyngeal cancer: a comparison between
      combined modality radio-chemotherapy and two variants of single modality altered
      fractionation radiotherapy.
AB  - PURPOSE: To compare outcomes in patients with locally advanced oropharyngeal
      cancer treated with radio-chemotherapy (RT-CT), accelerated fractionation
      radiotherapy (AccRT), or hypofractionated radiotherapy (HypoRT). METHODS AND
      MATERIALS: Subjects were 321 consecutive patients with newly diagnosed
      oropharyngeal cancer, Stage III or IVA/B, treated between January 2001 and
      December 2005 at the BC Cancer Agency with RT-CT (n = 157), AccRT (n = 57), or
      HypoRT (n = 107). Outcomes examined were disease-specific survival (DSS),
      locoregional control (LRC), overall survival (OS), rate of G-tube use, and rate
      of hospitalization for acute complications. RESULTS: Median follow-up was 3.4
      years. Three-year Kaplan-Meier DSS with RT-CT, AccRT, and HypoRT were 80%, 81%,
      and 74%, respectively (p = 0.219). Cox regression analysis identified treatment
      modality as a significant factor affecting DSS (p = 0.038). Compared with RT-CT,
      the hazard ratio (HR) for DSS was 1.0 with AccRT and 2.0 with HypoRT (p = 0.021).
      Kaplan-Meier pairwise comparisons found no significant difference in LRC and OS
      between RT-CT and AccRT. HypoRT was associated with significantly lower LRC (p =
      0.005) and OS (p = 0.008) compared with RT-CT. There were significant differences
      in the rates of G-tube use (p < 0.001) and of hospitalization (p = 0.036) among
      the three treatment groups, with the most frequent rates observed in the RT-CT
      group. CONCLUSIONS: In patients with locally advanced oropharyngeal cancer, AccRT
      conferred DSS, LRC, and OS comparable to that of RT-CT. Patients treated with RT
      CT experienced higher rates of treatment-related acute toxicities. HypoRT was
      associated with the least favorable outcomes.

PMID- 20675072
TI  - 10-year experience with I-125 prostate brachytherapy at the Princess Margaret
      Hospital: results for 1,100 patients.
AB  - PURPOSE: To report outcomes for 1,111 men treated with iodine-125 brachytherapy
      (BT) at a single institution. METHODS AND MATERIALS: A total of 1,111 men (median
      age, 63) were treated with iodine-125 prostate BT for low- or intermediate-risk
      prostate cancer between March 1999 and November 2008. Median prostate-specific
      antigen (PSA) level was 5.4 ng/ml (range, 0.9-26.1). T stage was T1c in 66% and
      T2 in 34% of patients. Gleason score was 6 in 90.1% and 7 or 8 in 9.9% of
      patients. Neoadjuvant hormonal therapy (2-6 months course) was used in 10.1% of
      patients and combined external radiotherapy (45 Gy) with BT (110 Gy) in 4.1% (n =
      46) of patients. Univariate and multivariate Cox proportional hazards were used
      to determine predictors of failure. RESULTS: Median follow-up was 42 months
      (range, 6-114), but for biochemical freedom from relapse, a minimum PSA test
      follow-up of 30 months was required (median 54; n = 776). There were 27 failures,
      yielding an actuarial 7-year disease-free survival rate of 95.2% (96 at risk
      beyond 84 months). All failures underwent repeat 12-core transrectal ultrasound 
      guided biopsies, confirming 8 local failures. On multivariate analysis, Gleason
      score was the only independent predictor of failure (p = 0.001; hazard ratio, 4.8
      (1.9-12.4). Median International Prostate Symptom score from 12 to 108 months
      ranged between 3 and 9. Of the men reporting baseline potency, 82.8% retained
      satisfactory erectile function beyond 5 years. CONCLUSION: Iodine-125 prostate BT
      is a highly effective treatment option for favorable- and intermediate-risk
      prostate cancer and is associated with maintenance of good urinary and erectile
      functions.

PMID- 20675073
TI  - Intensity-modulated radiotherapy for oral cavity squamous cell carcinoma:
      patterns of failure and predictors of local control.
AB  - PURPOSE: Few studies have evaluated the use of intensity-modulated radiotherapy
      (IMRT) for squamous cell carcinoma (SCC) of the oral cavity (OC). We report
      clinical outcomes and failure patterns for these patients. METHODS AND MATERIALS:
      Between October 2002 and June 2009, 37 patients with newly diagnosed SCC of the
      OC underwent postoperative (30) or definitive (7) IMRT. Twenty-five patients
      (66%) received systemic therapy. The median follow-up was 38 months (range, 10-87
      months). The median interval from surgery to RT was 5.9 weeks (range, 2.1-10.7
      weeks). RESULTS: Thirteen patients experienced local-regional failure at a median
      of 8.1 months (range, 2.4-31.9 months), and 2 additional patients experienced
      local recurrence between surgery and RT. Seven local failures occurred in-field
      (one with simultaneous nodal and distant disease) and two at the margin. Four
      regional failures occurred, two in-field and two out-of-field, one with
      synchronous metastases. Six patients experienced distant failure. The 3-year
      actuarial estimates of local control, local-regional control, freedom from
      distant metastasis, and overall survival were 67%, 53%, 81%, and 60% among
      postoperative patients, respectively, and 60%, 60%, 71%, and 57% among definitive
      patients. Four patients developed Grade >= 2 chronic toxicity. Increased surgery
      to RT interval predicted for decreased LRC (p = 0.04). CONCLUSIONS: Local
      regional control for SCC of the OC treated with IMRT with or without surgery
      remains unsatisfactory. Definitive and postoperative IMRT have favorable toxicity
      profiles. A surgery-to-RT interval of < 6 weeks improves local-regional control.
      The predominant failure pattern was local, suggesting that both improvements in
      target delineation and radiosensitization and/or dose escalation are needed.

PMID- 20675074
TI  - Adjuvant and definitive radiotherapy for adrenocortical carcinoma.
AB  - PURPOSE: To evaluate the impact of both adjuvant and definitive radiotherapy on
      local control of adrenocortical carcinoma. METHODS AND MATERIALS: Outcomes were
      analyzed from 58 patients with 64 instances of treatment for adrenocortical
      carcinoma at the University of Michigan's Multidisciplinary Adrenal Cancer
      Clinic. Thirty-seven of these instances were for primary disease, whereas the
      remaining 27 were for recurrent disease. Thirty-eight of the treatment regimens
      involved surgery alone, 10 surgery plus adjuvant radiotherapy, and 16 definitive
      radiotherapy for unresectable disease. The effects of patient, tumor, and
      treatment factors were modeled simultaneously using multiple variable Cox
      proportional hazards regression for associations with local recurrence, distant
      recurrence, and overall survival. RESULTS: Local failure occurred in 16 of the 38
      instances that involved surgery alone, in 2 of the 10 that consisted of surgery
      plus adjuvant radiotherapy, and in 1 instance of definitive radiotherapy. Lack of
      radiotherapy use was associated with 4.7 times the risk of local failure compared
      with treatment regimens that involved radiotherapy (95% confidence interval, 1.2
      19.0; p = 0.030). CONCLUSIONS: Radiotherapy seems to significantly lower the risk
      of local recurrence/progression in patients with adrenocortical carcinoma.
      Adjuvant radiotherapy should be strongly considered after surgical resection.

PMID- 20675075
TI  - Salvage reirradiaton with stereotactic body radiotherapy for locally recurrent
      head-and-neck tumors.
AB  - PURPOSE: In this study, we present our results of reirradiation of locally
      recurrent head-and-neck cancer with image-guided, fractionated, frameless
      stereotactic body radiotherapy technique. METHODS AND MATERIALS: From July 2007
      to February 2009, 46 patients were treated using the CyberKnife (Accuray,
      Sunnyvale, CA) at the Department of Radiation Oncology, Hacettepe University,
      Ankara, Turkey. All patients had recurrent, unresectable, and previously
      irradiated head-and-neck cancer. The most prominent site was the nasopharynx
      (32.6%), and the most common histopathology was epidermoid carcinoma. The
      planning target volume was defined as the gross tumor volume identified on
      magnetic resonance imaging and computed tomography. There were 22 female and 24
      male patients. Median age was 53 years (range, 19-87 years). The median tumor
      dose with stereotactic body radiotherapy was 30 Gy (range, 18-35 Gy) in a median
      of five (range, one to five) fractions. RESULTS: Of 37 patients whose response to
      therapy was evaluated, 10 patients (27%) had complete tumor regression, 11
      (29.8%) had partial response, and 10 (27%) had stable disease. Ultimate local
      disease control was achieved in 31 patients (83.8%). The overall survival was
      11.93 months in median (ranged, 11.4-17.4 months), and the median progression
      free survival was 10.5 months. One-year progression-free survival and overall
      survival were 41% and 46%, respectively. Grade II or greater long-term
      complications were observed in 6 (13.3%) patients. On follow-up, 8 (17.3%)
      patients had carotid blow-out syndrome, and 7 (15.2%) patients died of bleeding
      from carotid arteries. We discovered that this fatal syndrome occurred only in
      patients with tumor surrounding carotid arteries and carotid arteries receiving
      all prescribed dose. CONCLUSIONS: Stereotactic body radiotherapy is an appealing
      treatment option for patients with recurrent head-and-neck cancer previously
      treated with radiation to high doses. Good local control with considerable 1-year
      survival is achieved with a relatively high rate of morbidity and related
      mortality.

PMID- 20675077
TI  - Volumetric arc therapy and intensity-modulated radiotherapy for primary prostate
      radiotherapy with simultaneous integrated boost to intraprostatic lesion with 6
      and 18 MV: a planning comparison study.
AB  - PURPOSE: The aim of the present study was to compare intensity-modulated
      radiotherapy (IMRT) with volumetric arc therapy (VMAT), in the treatment of
      prostate cancer with maximal dose escalation to the intraprostatic lesion (IPL),
      without violating the organ-at-risk constraints. Additionally, the use of 6-MV
      photons was compared with 18-MV photons for all techniques. METHODS AND
      MATERIALS: A total of 12 consecutive prostate cancer patients with an IPL on
      magnetic resonance imaging were selected for the present study. Plans were made
      for three IMRT field setups (three, five, and seven fields) and one VMAT field
      setup (single arc). First, optimal plans were created for every technique using
      biologic and physical planning aims. Next, an additional escalation to the IPL
      was planned as high as possible without violating the planning aims of the first
      step. RESULTS: No interaction between the technique and photon energy (p=.928)
      occurred. No differences were found between the 6- and 18-MV photon beams, except
      for a reduction in the number of monitor units needed for 18 MV (p<.05). All
      techniques, except for three-field IMRT, allowed for dose escalation to a median
      dose of >=93+/-6 Gy (mean+/-standard deviation) to the IPL. VMAT was superior to
      IMRT for rectal volumes receiving 20-50 Gy (p<.05). CONCLUSION: VMAT allowed for
      dose escalation to the IPL with better sparing of the rectum than static three-,
      five-, and seven-field IMRT setups. High-energy photons had no advantage over low
      energy photons.

PMID- 20675076
TI  - Association between pulmonary uptake of fluorodeoxyglucose detected by positron
      emission tomography scanning after radiation therapy for non-small-cell lung
      cancer and radiation pneumonitis.
AB  - PURPOSE: To study the relationship between fluorodeoxyglucose (FDG) uptake in
      pulmonary tissue after radical radiation therapy (RT) and the presence and
      severity of radiation pneumonitis. METHODS AND MATERIALS: In 88 consecutive
      patients, (18)F-FDG-positron emission tomography was performed at a median of 70
      days after completion of RT. Patients received 60 Gy in 30 fractions, and all but
      15 had concurrent platinum-based chemotherapy. RT-induced pulmonary inflammatory
      changes occurring within the radiation treatment volume were scored, using a
      visual (0 to 3) radiotoxicity grading scale, by an observer blinded to the
      presence or absence of clinical radiation pneumonitis. Radiation pneumonitis was
      retrospectively graded using the Radiation Therapy Oncology Group (RTOG) scale by
      an observer blinded to the PET radiotoxicity score. RESULTS: There was a
      significant association between the worst RTOG pneumonitis grade occurring at any
      time after RT and the positron emission tomograph (PET) radiotoxicity grade (one
      sided p = 0.033). The worst RTOG pneumonitis grade occurring after the PET scan
      was also associated with the PET radiotoxicity grade (one-sided p = 0.035). For
      every one-level increase in the PET toxicity scale, the risk of a higher RTOG
      radiation pneumonitis score increased by approximately 40%. The PET radiotoxicity
      score showed no significant correlation with the duration of radiation
      pneumonitis. CONCLUSIONS: The intensity of FDG uptake in pulmonary tissue after
      RT determined using a simple visual scoring system showed significant correlation
      with the presence and severity of radiation pneumonitis. (18)F-FDG-PET may be
      useful in the prediction, diagnosis and therapeutic monitoring of radiation
      pneumonitis.

PMID- 20675078
TI  - Phase I trial of simultaneous in-field boost with helical tomotherapy for
      patients with one to three brain metastases.
AB  - PURPOSE: Stereotactic radiosurgery is an alternative to surgical resection for
      selected intracranial lesions. Integrated image-guided intensity-modulated
      capable radiotherapy platforms such as helical tomotherapy (HT) could potentially
      replace traditional radiosurgery apparatus. The present study's objective was to
      determine the maximally tolerated dose of a simultaneous in-field boost
      integrated with whole brain radiotherapy for palliative treatment of patients
      with one to three brain metastases using HT. METHODS AND MATERIALS: The
      inclusion/exclusion criteria and endpoints were consistent with the Radiation
      Therapy Oncology Group 9508 radiosurgery trial. The cohorts were constructed with
      a 3 + 3 design; however, additional patients were enrolled in the lower dose
      tolerable cohorts during the toxicity assessment periods. Whole brain
      radiotherapy (30 Gy in 10 fractions) was delivered with a 5-30-Gy (total lesion
      dose of 35-60 Gy in 10 fractions) simultaneous in-field boost delivered to the
      brain metastases. The maximally tolerated dose was determined by the frequency of
      neurologic Grade 3-5 National Cancer Institute Common Toxicity Criteria, version
      3.0, dose-limiting toxicity events within each Phase I cohort. RESULTS: A total
      of 48 patients received treatment in the 35-Gy (n = 3), 40-Gy (n = 16), 50-Gy (n
      = 15), 55-Gy (n = 8), and 60-Gy (n = 6) cohorts. No patients experienced dose
      limiting toxicity events in any of the trial cohorts. The 3-month RECIST
      assessments available for 32 of the 48 patients demonstrated a complete response
      in 2, a partial response in 16, stable disease in 6, and progressive disease in 8
      patients. CONCLUSION: The delivery of 60 Gy in 10 fractions to one to three brain
      metastases synchronously with 30 Gy whole brain radiotherapy was achieved without
      dose-limiting central nervous system toxicity as assessed 3 months after
      treatment. This approach is being tested in a Phase II efficacy trial.

PMID- 20675080
TI  - Fractionated stereotactic radiotherapy in the treatment of vestibular schwannoma
      (acoustic neuroma): predicting the risk of hydrocephalus.
AB  - PURPOSE: To determine the incidence and predictive factors for the development of
      hydrocephalus in patients with acoustic neuromas (AN) treated with fractionated
      stereotactic radiotherapy. PATIENTS AND METHODS: Seventy-two patients with AN
      were treated with fractionated stereotactic radiotherapy between 1998 and 2007
      (45-50 Gy in 25-30 fractions over 5 to 6 weeks). The pretreatment MRI scan was
      assessed for tumor characteristics and anatomic distortion independently of
      subsequent outcome and correlated with the risk of hydrocephalus. RESULTS: At a
      median follow-up of 49 months (range, 1-120 months), 5-year event-free survival
      was 95%. Eight patients (11%) developed hydrocephalus within 19 months of
      radiotherapy, which was successfully treated. On univariate analysis,
      pretreatment factors predictive of hydrocephalus were maximum diameter (p =
      0.005), proximity to midline (p = 0.009), displacement of the fourth ventricle (p
      = 0.02), partial effacement of the fourth ventricle (p < 0.001), contact with the
      medulla (p = 0.005), and more brainstem structures (p = 0.004). On multivariate
      analysis, after adjusting for fourth ventricular effacement, no other variables
      remained independently associated with hydrocephalus formation. CONCLUSIONS:
      Fractionated stereotactic radiotherapy results in excellent tumor control of AN,
      albeit with a risk of developing hydrocephalus. Patients at high risk, identified
      as those with larger tumors with partial effacement of the fourth ventricle
      before treatment, should be monitored more closely during follow-up. It would
      also be preferable to offer treatment to patients with progressive AN while the
      risk of hydrocephalus is low, before the development of marked distortion of
      fourth ventricle before tumor diameter significantly exceeds 2 cm.

PMID- 20675079
TI  - Metronomic small molecule inhibitor of Bcl-2 (TW-37) is antiangiogenic and
      potentiates the antitumor effect of ionizing radiation.
AB  - PURPOSE: To investigate the effect of a metronomic (low-dose, high-frequency)
      small-molecule inhibitor of Bcl-2 (TW-37) in combination with radiotherapy on
      microvascular endothelial cells in vitro and in tumor angiogenesis in vivo.
      METHODS AND MATERIALS: Primary human dermal microvascular endothelial cells were
      exposed to ionizing radiation and/or TW-37 and colony formation, as well as
      capillary sprouting in three-dimensional collagen matrices, was evaluated.
      Xenografts vascularized with human blood vessels were engineered by
      cotransplantation of human squamous cell carcinoma cells (OSCC3) and human dermal
      microvascular endothelial cells seeded in highly porous biodegradable scaffolds
      into the subcutaneous space of immunodeficient mice. Mice were treated with
      metronomic TW-37 and/or radiation, and tumor growth was evaluated. RESULTS: Low
      dose TW-37 sensitized primary endothelial cells to radiation-induced inhibition
      of colony formation. Low-dose TW-37 or radiation partially inhibited endothelial
      cell sprout formation, and in combination, these therapies abrogated new
      sprouting. Combination of metronomic TW-37 and low-dose radiation inhibited tumor
      growth and resulted in significant increase in time to failure compared with
      controls, whereas single agents did not. Notably, histopathologic analysis
      revealed that tumors treated with TW-37 (with or without radiation) are more
      differentiated and showed more cohesive invasive fronts, which is consistent with
      less aggressive phenotype. CONCLUSIONS: These results demonstrate that metronomic
      TW-37 potentiates the antitumor effects of radiotherapy and suggest that patients
      with head and neck cancer might benefit from the combination of small molecule
      inhibitor of Bcl-2 and radiation therapy.

PMID- 20675081
TI  - A matched control analysis of adjuvant and salvage high-dose postoperative
      intensity-modulated radiotherapy for prostate cancer.
AB  - PURPOSE: It is unclear whether immediate adjuvant radiotherapy for high-risk
      disease at prostatectomy (capsule perforation, seminal vesicle invasion, and/or
      positive surgical margins) is equivalent to delayed salvage radiotherapy at
      biochemical recurrence. We performed a matched case analysis comparing high-dose
      adjuvant intensity modulated radiotherapy (A-IMRT) with salvage IMRT (S-IMRT).
      METHODS AND MATERIALS: One hundred forty-four patients with high-risk disease at
      prostatectomy were referred for A-IMRT, and 134 patients with high-risk disease
      were referred at biochemical recurrence (rising prostate-specific antigen [PSA],
      following prostatectomy, above 0.2 ng/ml) for S-IMRT. Patients were matched in a
      1:1 ratio according to preoperative PSA level, Gleason score, and pT stage.
      Median doses of 74 Gy and 76 Gy were prescribed for A-IMRT and S-IMRT,
      respectively. We report biochemical relapse free survival (bRFS) rates using the
      Kaplan-Meier method. Univariate and multivariate analyses were used to examine
      tumour- and treatment-related factors. RESULTS: A total of 178 patients were
      matched (89:89). From the end of radiotherapy, the median follow-up was 36 months
      for both groups. The 3-year bRFS rate for the A-IMRT group was 90% compared to
      65% for the S-IMRT group (p < 0.05). On multivariate analysis, S-IMRT, Gleason
      grades of >= 4+3, perineural invasion, preoperative PSA level of >= 10 ng/ml, and
      omission of androgen deprivation (AD) were independent predictors for a reduced
      bRFS (p < 0.05). From the date of surgery, the median follow-up was 43 and 60
      months for A-IMRT and S-IMRT, respectively. The 3-year bRFS rate for A-IMRT was
      91% compared to 79% for S-IMRT (p < 0.05). On multivariate analysis, Gleason
      grades of >= 4+3, perineural invasion, and omission of AD were independent
      predictors for a reduced bRFS (p < 0.05). S-IMRT was no longer an independent
      prognostic factor (p = 0.08). CONCLUSIONS: High-dose A-IMRT significantly
      improves 3-year bRFS compared to S-IMRT. Gleason grades of >= 4+3, perineural
      invasion, and omission of AD were independent prognostic factors for a decreased
      bRFS, both from the dates of surgery and from radiotherapy.

PMID- 20675082
TI  - Rectal inoculation of sheep with E. coli O157:H7 results in persistent infection
      in the absence of a protective immune response.
AB  - Escherichia coli (E. coli) O157:H7 can cause haemorrhagic colitis and the
      haemolytic uremic syndrome in humans. Ruminants are the main reservoir for this
      bacterium: they can harbour the bacteria in the gastrointestinal tract without
      showing clinical symptoms. The reason for this persistence is still unclear,
      although it has been suggested that E. coli O157:H7 can suppress the immune
      system. To investigate the effects on the immune system of ruminants, an
      infection model is needed that mimics a long-term infection as it can occur in
      both sheep and cattle. As the terminal rectum has recently been identified as a
      primary colonisation site in cattle, we developed a rectal inoculation model for
      sheep and used this model to study immune responses against selected virulence
      factors of E. coli O157:H7 (intimin, EspA and EspB). Sheep were infected and re
      infected when E. coli O157:H7 excretion was no longer detectable. The animals did
      not develop serum or local antibody responses but showed a cellular response
      against EspA and intimin respectively 9 and 16 days after infection. This
      response was also present 5 days after re-infection, albeit lower, and did not
      prevent animals from being re-infected. These results demonstrate that E. coli
      O157:H7 can be persistently present in the large intestine of sheep without
      inducing a clear protective immune response.

PMID- 20675083
TI  - Elevated expression of four apolipoprotein genes during the 32-35 week gestation
      window in the human developing lung.
AB  - BACKGROUND: Co-expression of four apolipoproteins with a sex difference was
      observed in the mouse developing lung with an increase during the day of the
      surge of surfactant synthesis and a causal relationship was proposed. AIMS: To
      determine whether these apolipoproteins and lipoprotein lipase (LPL) are
      expressed in the human fetal lung. To compare the distribution patterns of apoC
      II and LPL proteins at different developmental ages. STUDY DESIGN: Real-time PCR
      with RNA samples and immunohistochemistry with tissues from lungs of fetuses
      deceased between 19 and 40 weeks' pregnancy. RESULTS: Elevated apolipoprotein A-I
      (apoA-I), apoA-II, apoC-II, and apoH expression was observed only during a short
      gestation time window from 32 to 35 weeks' gestation. LPL was expressed at
      relatively constant levels over gestation time. The gene encoding for the
      essential co-factor of LPL, apoC-II, was expressed at similar levels than LPL
      gene only during the 32-35 week gestation window. ApoC-II and LPL protein
      distribution vary according to gestation time, with obvious co-localization in
      capillaries at 32 weeks' gestation, but not in samples collected at 22-24 weeks'
      gestation. CONCLUSIONS: ApoA-I, apoA-II, apoC-II, and apoH genes are expressed
      with a human-specific narrow peak of elevated expression in late gestation.
      Specific and developmental time-dependent distribution profiles were observed for
      apoC-II and LPL proteins. The 32-35 weeks' gestation window, where high levels of
      expression of apolipoproteins and co-localization of apoC-II and LPL protein were
      observed, correlates with the reported decrease in the incidence and severity of
      respiratory distress syndrome (RDS) consequently to the surge of surfactant
      synthesis.

PMID- 20675084
TI  - Maternal breast milk odour induces frontal lobe activation in neonates: a NIRS
      study.
AB  - We used near-infrared spectroscopy (NIRS) to examine differences in neonates'
      orbito-frontal cortical activation in response to the odours of maternal breast
      milk and formula milk in terms of changes in the oxygenation of cerebral blood
      flow. Twenty-six healthy neonates were tested in their cribs while they slept in
      a silent room. The neonates were exposed to each olfactory stimulus by an
      experimenter. NIRS monitoring was performed using optodes placed above the
      bilateral anterior orbito-frontal gyri. The differences in oxygenated haemoglobin
      (oxy-Hb) values between baseline and stimulation were defined as the change in
      oxy-Hb. The degrees of change were calculated by an analysis of variance (ANOVA).
      A 2 (stimulus: breast milk and formula milk) * 2 (probe location: right and left)
      ANOVA showed that the odour of maternal breast milk (right/left: M=0.28/0.48)
      induced a significantly (F=6.36, p<0.05) greater increase in the oxygenated blood
      of the orbito-frontal region than did the odour of formula milk (right/left: M=
      0.03/-0.07). Differences in the intensity of odour had no significant influence
      on the blood oxygenation of the orbito-frontal region. Maternal breast milk odour
      increased oxygenated blood flow in the orbito-frontal region to a greater extent
      than did formula milk odour. These results suggest that neonates can distinguish
      between the odours of maternal breast milk versus formula.

PMID- 20675086
TI  - Dysplastic hepatic nodules: radiological abnormalities and histopathological
      correlations.
AB  - Pathological studies of explanted cirrhotic livers have made it possible to
      define precisely the principal morphological characteristics of the transitional
      stages of the regenerative nodule to dysplastic nodule to hepatocellular
      carcinoma. The aim of our study was to examine the imaging features of
      histologically proven dysplastic nodules and to compare them with their
      histopathological features. A large majority (63%) of the dysplastic nodules in
      our series was hypervascular and 16% had the classic appearance of hepatocellular
      carcinoma. Even if the management of a high-grade dysplastic nodule differs
      little from that of a hepatocellular carcinoma, it is important to remember that
      not all hypervascular nodules in a cirrhotic liver are necessarily a
      hepatocellular carcinoma or a high-grade dysplastic nodule.

PMID- 20675085
TI  - Maternal and paternal height and BMI and patterns of fetal growth: the Pune
      Maternal Nutrition Study.
AB  - We examined the differential associations of each parent's height and BMI with
      fetal growth, and examined the pattern of the associations through gestation.
      Data are from 557 term pregnancies in the Pune Maternal Nutrition Study. Size and
      conditional growth outcomes from 17 to 29 weeks to birth were derived from
      ultrasound and birth measures of head circumference, abdominal circumference,
      femur length and placental volume (at 17 weeks only). Parental height was
      positively associated with fetal head circumference and femur length. The
      associations with paternal height were detectible earlier in gestation (17-29
      weeks) compared to the associations with maternal height. Fetuses of mothers with
      a higher BMI had a smaller mean head circumference at 17 weeks, but caught up to
      have larger head circumference at birth. Maternal but not paternal BMI, and
      paternal but not maternal height, were positively associated with placental
      volume. The opposing associations of placenta and fetal head growth with maternal
      BMI at 17 weeks could indicate prioritisation of early placental development,
      possibly as a strategy to facilitate growth in late gestation. This study has
      highlighted how the pattern of parental-fetal associations varies over gestation.
      Further follow-up will determine whether and how these variations in
      fetal/placental development relate to health in later life.

PMID- 20675087
TI  - Whole tumour first-pass perfusion using a low-dose method with 64-section
      multidetector row computed tomography in oesophageal squamous cell carcinoma.
AB  - PURPOSE: To propose a low-dose method at tube current-time product of 50 mAs for
      whole tumour first-pass perfusion of oesophageal squamous cell carcinoma using 64
      section multidetector row computed tomography (MDCT), and to assess the original
      image quality and accuracy of perfusion parameters. MATERIALS AND METHODS: Fifty
      nine consecutive patients with confirmed oesophageal squamous cell carcinomas
      were enrolled into our study, and underwent whole tumour first-pass perfusion
      scan with 64-section MDCT at 50 mAs. Image data were statistically reviewed
      focusing on original image quality demonstrated by image-quality scores and
      signal-to-noise (S/N) ratios; and perfusion parameters including perfusion (PF,
      in ml/min/ml), peak enhanced density (PED, in HU), time to peak (TTP, in seconds)
      and blood volume (BV, in ml/100 g) for the tumour. To test the interobserver
      agreement of perfusion measurements, perfusion analyses were repeatedly
      performed. RESULTS: Original image-quality scores were 4.71+/-0.49 whereas S/N
      ratios were 5.21+/-2.05, and the scores were correlated with the S/N ratios
      (r=0.465, p<0.0001). Mean values for PF, PED, TTP and BV of the tumour were
      33.27+/-24.15 ml/min/ml, 24.06+/-9.87 HU, 29.42+/-8.61 s, and 12.45+/-12.22
      ml/100 g, respectively. Intraclass correlation coefficient between the replicated
      measurements of each perfusion parameter was greater than 0.99, and mean
      difference of the replicated measurements of each parameter was close to zero.
      CONCLUSION: Whole tumour first-pass perfusion with 64-section MDCT at low-dose
      radiation could be reproducible to assess microcirculation in oesophageal
      squamous cell carcinoma without compromising subjective original image quality of
      the tumour.

PMID- 20675088
TI  - Isolation, genetic and functional characterization of novel soil nirK-type
      denitrifiers.
AB  - Denitrification, the reduction of nitrogen oxides (NO(3)(-) and NO(2)(-)) to N(2)
      via the intermediates NO and N(2)O, is crucial for nitrogen turnover in soils.
      Cultivation-independent approaches that applied nitrite reductase genes
      (nirK/nirS) as marker genes to detect denitrifiers showed a predominance of genes
      presumably derived from as yet uncultured organisms. However, the phylogenetic
      affiliation of these organisms remains unresolved since the ability to denitrify
      is widespread among phylogenetically unrelated organisms. In this study,
      denitrifiers were cultured using a strategy to generally enrich soil
      microorganisms. Of 490 colonies screened, eight nirK-containing isolates were
      phylogenetically identified (16S rRNA genes) as members of the Rhizobiales. A
      nirK gene related to a large cluster of sequences from uncultured bacteria mainly
      retrieved from soil was found in three isolates classified as Bradyrhizobium sp.
      Additional isolates were classified as Bradyrhizobium japonicum and Bosea sp.
      that contained nirK genes also closely related to the nirK from these strains.
      These isolates denitrified, albeit with different efficiencies. In Devosia sp.,
      nirK was the only denitrification gene detected. Two Mesorhizobium sp. isolates
      contained a nirK gene also related to nirK from cultured Mesorhizobia and
      uncultured soil bacteria but no gene encoding nitric oxide or nitrous oxide
      reductase. These isolates accumulated NO under nitrate-reducing conditions
      without growth, presumably due to the lethal effects of NO. This showed the
      presence of a functional nitrite reductase but lack of a nitric oxide reductase.
      In summary, similar nirK genotypes recurrently detected mainly in soils likely
      originated from Rhizobia, and functional differences were presumably strain
      dependent.

PMID- 20675089
TI  - Chiral analysis of pharmaceuticals by capillary electrophoresis using antibiotics
      as chiral selectors.
AB  - The review summarizes the use of the chiral capillary electrophoresis (CE) with
      different class of antibiotics as chiral selectors in the pharmaceutical field.
      Basic factors influencing the enantioseparation are shortly discussed. Non
      aqueous capillary electrophoresis is also included as well as the coupling of CE
      to MS. The selection of a chiral selector according the ionic state and structure
      of the analyte is described. Summary of pharmaceutical applications of chiral CE
      is given.

PMID- 20675090
TI  - Determination of SNX-2112, a selective Hsp90 inhibitor, in plasma samples by high
      performance liquid chromatography and its application to pharmacokinetics in
      rats.
AB  - A sensitive and specific reversed-phase high-performance liquid chromatography
      method with ultraviolet detection has been developed and validated for the
      identification and quantification of SNX-2112 in rat plasma. Following sample
      preparation using liquid-liquid extraction, the analytes were separated by the
      mobile phase acetonitrile-water (40:60, v/v) with an Agilent RP-HPLC column
      (ZORBAX SB-C18, 5 microm, 4.6 mm x 250 mm) at a flow rate of 1 ml/min, column
      temperature of 30 degrees C and detection wavelength of 251 nm. The retention
      time of SNX-2112 was 11.2 min. A good linear relationship was obtained in the
      concentration range studied (0.07-21 microg/ml, R(2)>0.9982), and the LLOD and
      LLOQ for SNX-2112 were 0.02 and 0.07 microg/ml, respectively. The mean absolute
      recovery of SNX-2112 in plasma ranged from 88.58 to 99.61% at the studied
      concentrations. The intra- and inter-batch relative standard deviations were 1.7
      3.5 and 1.9-4.4%, respectively. This method was successfully applied to
      pharmacokinetic studies in rats after intravenous administration of SNX-2112.

PMID- 20675091
TI  - Product of alaptide synthesis: determination of the absolute configuration.
AB  - Alaptide is the active substance of the veterinary dermatological ointment
      ALAPTID and a potential drug in human medicine. Electronic circular dichroism
      spectroscopy (ECD), transparent spectral region optical rotation (OR), and ab
      initio calculations were employed to determine the absolute configuration of
      alaptide. No X-ray structural data determining the absolute configuration were
      available. It was not possible to employ vibrational circular dichroism
      spectroscopy (VCD), because alaptide was not sufficiently soluble in common
      solvents used in VCD spectroscopy to generate reliable spectra. Both ECD spectra
      and OR values of alaptide solution were in good agreement with predicted data and
      determined unambiguously the absolute configuration of alaptide synthesized from
      (S)-alanine as being (S).

PMID- 20675092
TI  - Sacral insufficiency fractures: an easily overlooked cause of back pain in the
      ED.
AB  - Sacral insufficiency fractures are an important and treatable cause of severe
      back pain. Despite publication of several case reports since its original
      description in 1982, awareness of these injuries remains inadequate in emergency
      medicine. Most patients are elderly women presenting with intractable lower back
      pain. Postmenopausal osteoporosis is the most significant risk factor. Marked
      sacral tenderness is common. Neurologic impairment is rarely detectable. Routine
      radiography of the spine and pelvis is usually inconclusive. Computed tomography
      remains the diagnostic modality of choice. Treatment is usually conservative.

PMID- 20675093
TI  - Nontraumatic massive right-sided Bochdalek hernia in an adult: an unusual
      presentation.
AB  - Diaphragmatic hernias in adults usually pose a diagnostic challenge; the
      presentations are varied and range from acute abdominal pain with features of gut
      obstruction, pleuritic chest pain, breathlessness, to a pregnant woman with pain
      abdomen. The usual cause in adults is posttraumatic. Because of varied
      presentations, the diagnosis is often delayed. We present a case of a young woman
      who presented with sudden-onset breathlessness with similar episodes in the past
      and no history of trauma, who proved to be having a right-sided diaphragmatic
      hernia. This case is reported not only because of rarity of nontraumatic right
      sided Bochdalek hernias in adults, but also because of peculiar presentation and
      history.

PMID- 20675094
TI  - Ventricular fibrillation after correct pacing in digoxin intoxication.

PMID- 20675095
TI  - Identifying patient information needs about cancer clinical trials using a
      Question Prompt List.
AB  - OBJECTIVE: Question Prompt Lists (QPLs) have demonstrated significant promise in
      facilitating communication in general, surgical and palliative oncology settings
      yet have not been tested in the oncology clinical trial setting. We aimed to
      develop a targeted QPL for Clinical Trials (QPL-CT). METHODS: Breast, lung, and
      genitourinary cancer patients who either had (trial experienced) or had not
      (trial naive) participated in a clinical trial joined focus groups to help
      develop and explore the acceptability of a QPL-CT. Clinicians also participated
      in separated focus groups. Focus groups were audio-recorded and transcribed. We
      explored patients' trial information needs and views about the utility of the QPL
      CT. RESULTS: Patients focused on four trial information needs: understanding
      foundational information, conflict of interest issues and financial implications
      of trial participation. Of note, experienced patients need to personalize
      foundational information. CONCLUSION: Patient information needs varied
      considerably and were influenced by trial experience. Patients valued the QPL-CT
      as an aid to gathering new trial information and ensuring that their information
      needs were met. PRACTICE IMPLICATIONS: Physicians need to carefully elicit
      patient information needs and tailor trial information to meet these needs. The
      QPL-CT, may be of great benefit during clinical trial discussions.

PMID- 20675096
TI  - "Practicing medicine": patient perceptions of physician communication and the
      process of prescription.
AB  - OBJECTIVE: This study explores patient perceptions of physician communication
      regarding prescription medications and develops a theory of the effects of
      perceived physician communication on the patient decision-making process of
      medication taking. METHODS: Using a grounded theory approach, this study
      systematically analyzed patient narratives of communication with physicians
      regarding prescription medications and the patient's resulting medication taking
      and adherence behavior. RESULTS: Participants described concern about side
      effects, lack of perceived need for medications, and healthcare system factors as
      barriers to medication adherence. Overall, participants seemed to assess the
      utility of communication about these issues based on their perceptions of their
      physician as the source of the message. CONCLUSION: The theory generated here
      includes patient assessments of their physician's credibility (trustworthiness
      and expertise) as a critical influence in how chronically-ill patients process
      information about the need for prescribed therapy. Trial and error to find
      appropriate medications seemed to deteriorate patients' perceptions of their
      physicians' credibility. PRACTICE IMPLICATIONS: A practical application of this
      theory is the recommendation for physicians to increase perceived expertise by
      clearly outlining treatment processes at the outset of treatment, presenting
      efficacy and timeline expectations for finding appropriate medications.

PMID- 20675097
TI  - How serious of a problem is staff turnover in substance abuse treatment? A
      longitudinal study of actual turnover.
AB  - In the substance abuse treatment field, the annual turnover rate is cited as
      being anywhere between 19% and 50% (J.A. Johnson & P.M. Roman, 2002; S.L. Gallon,
      R.M. Gabriel, J.R.W. Knudsen, 2003; H.K. Knudsen, J.A. Johnson, & P.M. Roman,
      2003; A.T. McLellan, D. Carise, & H.D. Kleber, 2003). However, no research to
      date has evaluated these claims by tracking turnover longitudinally using
      organizational turnover data from substance abuse treatment centers. This
      research presents the results of a longitudinal study designed to systematically
      examine actual turnover among counselors and clinical supervisors. Twenty-seven
      geographically dispersed treatment organizations, serving a wide range of clients
      in the public and private sector, provided data for the study over a 2-year time
      span (2008-2009). The annual turnover rate was 33.2% for counselors and 23.4% for
      clinical supervisors. For both groups, the majority of turnover was voluntary
      (employee-initiated). Specific reasons for turnover were largely consistent
      across the two groups, with the most common reason being a new job or new
      opportunity. The findings are discussed in terms of the unique employment context
      of substance abuse treatment. Practical recommendations are also discussed to
      help stem the tide of turnover in the field of substance abuse treatment.

PMID- 20675098
TI  - [Albumin in sepsis].
AB  - Human serum albumin is a small (66kD) globular protein representing over 60 % of
      the total plasma protein content. It is made up of 585 amino 6 acids and contains
      35 cysteine residues forming disulfide bridges that contribute to its overall
      tertiary structure. It has a free cysteine-derived thiol group at Cys-34, which
      accounts for 80 % of its redox activity. Physiologically, serum albumin exists in
      a reduced form with a free thiol contributing to its antioxidant properties. It
      is synthesized primarily in the liver and is an acute-phase protein. It is a
      multifunctional plasma protein ascribed ligand-binding and transport properties
      as well as antioxidants and enzymatic functions. It maintains colloid osmotic
      pressure, modulates inflammatory response and may influence oxidative damage.
      Hypoalbuminemia is common in the intensive care unit and may be due to decreased
      synthesis by the liver and/or to increased losses or increased proteolysis and
      clearance. Although albumin was long used to control vascular collapse in
      critically ill patients, the evidence suggests that it does not offer a benefit
      over crystalloid solutions in vascular collapse. However, human serum albumin is
      an important circulating antioxidant and it may be beneficial in critically ill
      patients to limit oxidative damage. A number of studies suggest that in specific
      groups of hypoalbuminemic critically ill patients, albumin administration may
      have beneficial effects on organ function, although the exact mechanisms remain
      undefined. Further trials are needed to confirm theses observations and to
      clearly demonstrate whether albumin should be administered in critically ill
      patients with hypoalbuminemia.

PMID- 20675099
TI  - DSM-IV criteria for childhood separation anxiety disorder: informant, age, and
      sex differences.
AB  - BACKGROUND: The present study examines frequency of DSM-IV symptom and diagnostic
      criteria for separation anxiety disorder (SAD) by informant, age, and sex.
      METHODS: Children aged 4-15 years with a primary DSM-IV diagnosis of SAD (N=106)
      were assessed using structured diagnostic interviews (Kinder-DIPS; DSM-IV-TR
      Version). Frequency of DSM-IV symptom and diagnostic criteria were examined as a
      function of informant and child characteristics, along with impairment and
      distress ratings. RESULTS: The most frequently reported symptoms were separation
      related distress, avoidance of being alone/without an adult and sleeping away
      from caregivers or from home, with nightmares the least frequently endorsed
      criterion. Child report did not yield any significant sex or age differences.
      However, parent report revealed greater reluctance or avoidance of school
      attendance for girls than boys, and for younger children (<8 years). Parent
      report indicated greater symptom-related impairment than child report, and the
      number of symptoms was correlated with impairment based on parent report, and
      with distress based on child report. CONCLUSIONS: The primary indicators of SAD
      appear to be separation distress, avoidance of being alone, and sleeping away
      from caregivers. Findings suggest that parents may be best placed to determine
      impairment, while children may be the most accurate reporters of more covert
      internal distress. Implications for clinicians are that reports from multiple
      informants should be used to gain the most comprehensive information about
      childhood SAD.

PMID- 20675100
TI  - Genetic seizure susceptibility underlying acute encephalopathies in childhood.
AB  - We herein investigated risk factors of pediatric acute encephalopathy (AE)
      regarding the hitherto uncharacterized genetic background of seizure
      susceptibility underlying the pathogenesis of AE. The study included 15 patients
      with a history of various types of AE in childhood. We undertook the mutational
      analysis of the neuronal sodium channel alpha 1 subunit (SCN1A) gene which is the
      most representative gene for hyperthermia-induced seizure susceptibility. Six
      patients (40%) had a positive family history of seizures or AE, especially
      febrile seizures, in first- or second-degree relatives. The SCN1A-R1575C mutation
      was detected in a patient with a history of acute encephalitis with refractory,
      repetitive partial seizures (AERRPS) and also in the patient's apparently healthy
      father. In the present study, dense familial seizure predisposition was present
      in the patients with AE. Although the presence of seizure susceptibility alone is
      insufficient to cause AE, it can exacerbate seizures and the subsequent
      development of inflammatory reactions in the brain when environmental factors are
      included. Genetic seizure susceptibility may contribute to some types of AE in
      childhood.

PMID- 20675102
TI  - Electrochemical and spectral study on the effects of Al(III) and nano-Al13
      species on glutamate dehydrogenase activity.
AB  - A functionalized multi-wall nanotube (MWNT) modified glass carbon electrode (GCE)
      was used to study the effects of aluminum species on glutamate dehydrogenase
      (GLDH) activity by monitoring amperometric i-t curve for the oxidation of the
      enzymatically generated NADH. The conformational changes of the coenzyme
      nicotinamide adenine dinucleotide (NAD(+)) induced by Al(III) and nanometer-sized
      tridecameric aluminum polycation (nano-Al(13)) were investigated by the
      fluorescence technique. The results showed that the electrochemical method may be
      a potential tool to investigate the activity of enzymes in the biological system.
      It may also be useful in studying the effects of nano-sized aluminum compounds on
      biomolecules in order to discuss their safety to the environment and human.

PMID- 20675101
TI  - MicroRNA expression profiling in the prefrontal cortex of individuals affected
      with schizophrenia and bipolar disorders.
AB  - MicroRNAs (miRNAs) are a large family of small non-coding RNAs which negatively
      control gene expression at both the mRNA and protein levels. The number of miRNAs
      identified is growing rapidly and approximately one-third is expressed in the
      brain where they have been shown to affect neuronal differentiation, synaptosomal
      complex localization and synapse plasticity, all functions thought to be
      disrupted in schizophrenia. Here we investigated the expression of 667 miRNAs
      (miRBase v.13) in the prefrontal cortex of individuals with schizophrenia (SZ, N
      = 35) and bipolar disorder (BP, N = 35) using a real-time PCR-based Taqman Low
      Density Array (TLDA). After extensive QC steps, 441 miRNAs were included in the
      final analyses. At a FDR of 10%, 22 miRNAs were identified as being
      differentially expressed between cases and controls, 7 dysregulated in SZ and 15
      in BP. Using in silico target gene prediction programs, the 22miRNAs were found
      to target brain specific genes contained within networks overrepresented for
      neurodevelopment, behavior, and SZ and BP disease development. In an initial
      attempt to corroborate some of these predictions, we investigated the extent of
      correlation between the expressions of hsa-mir-34a, -132 and -212 and their
      predicted gene targets. mRNA expression of tyrosine hydroxylase (TH),
      phosphogluconate dehydrogenase (PGD) and metabotropic glutamate receptor 3 (GRM3)
      was measured in the SMRI sample. Hsa-miR-132 and -212 were negatively correlated
      with TH (p = 0.0001 and 0.0017) and with PGD (p = 0.0054 and 0.017,
      respectively).

PMID- 20675103
TI  - A novel technique for producing durable multifunctional textiles using
      nanocomposite coating.
AB  - The treatment of textiles with Ag/TiO(2) nanoparticles causes a brownish color
      that limits the application of this otherwise good composite. In this paper, a
      novel method is introduced to overcome this problem. To this end, the effect of
      various concentrations of cross-linkable polysiloxane (XPs) and Ag mixed with XPs
      on TiO(2) treated fabrics has been investigated. The results reveal the
      performance of the method in the application of Ag and TiO(2) nanoparticles
      separately. In addition to the major effect of XPs on durability, the synergistic
      effect of applying XPs, especially Ag mixed with XPs, on TiO(2) has been
      confirmed. Unexpectedly, increasing the concentration of XPs not only did not
      limit the TiO(2) activity but allowed light absorption by the TiO(2) particles
      due to the low refractive index of XPs. Therefore, XPs treatment can be helpful
      for increasing the bioactivity and the general photo-catalytic activity of
      TiO(2). The results also showed that the hydrophilicity-hydrophobicity of treated
      substrate can be adjusted over a broad range by controlling the concentrations of
      these two nanoparticles and the XPs ratio. Other characteristics of treated
      fabrics such as antibacterial, self-cleaning, stain photo-degradability, UV
      protection, air permeability and washing durability were also investigated.

PMID- 20675104
TI  - Electrokinetic flow near an undulated, charged surface.
AB  - In this study, using the iterative finite difference method, the effect of an
      irregular condition at boundary, the surface undulation, in a charged surface
      system on the two dimensional electrokinetic flow near the surface is analyzed.
      The results reveal that, for the electrokinetic flow, the undulation of charged
      surface may have two major effects: one is that it changes the flow pattern of
      electrolyte solution, especially in the region close to the undulated surface;
      the other is that, due to the increase of effective surface area, the magnitude
      of velocity field may be increased considerably. In addition, when either the
      amplitude of undulation is increased, or the period of undulation is decreased,
      both the maximum velocity and the tangential flow rate will be raised to an
      extent. This is important for applications, for example, the electrophoresis of a
      biological cell, the electroosmosis of electrolyte solution in a micro-channel,
      etc.

PMID- 20675105
TI  - Ag/Al(OH)3 mesoporous nanocomposite film as antibacterial agent.
AB  - In this study, Ag/Al(OH)(3) mesoporous nanocomposite film was fabricated for
      antibacterial agent. As a matrix, a mesoporous Al(OH)(3) layer was prepared by
      alkali surface modification of an Al substrate. Subsequently, mesoporous
      Al(OH)(3) matrix was immersed in a polyol solution for 4h at an elevated
      temperature to deposit silver nanoparticles (Ag NPs) by in situ dispersion. The
      Al(OH)(3) porous matrix had flaky crystals weaved and covered all substrate
      surface so that the specific surface area was considerably increased because of
      voids having several tens of nanometers between the flakes. After in situ
      dispersion of Ag NPs by polyol process, the Ag NPs were nucleated and grown at
      the surface of mesoporous Al(OH)(3) layer with tight binding. In antibacterial
      activity, Ag/Al(OH)(3) mesoporous nanocomposite film demonstrated an excellent
      bacterial growth inhibition property. It is believed that the Ag/Al(OH)(3)
      mesoporous nanocomposite film is suitable for the antibacterial agent in a wide
      variety of biomedical applications.

PMID- 20675106
TI  - Evolutionary-driven support vector machines for determining the degree of liver
      fibrosis in chronic hepatitis C.
AB  - OBJECTIVE: Hepatic fibrosis, the principal pointer to the development of a liver
      disease within chronic hepatitis C, can be measured through several stages. The
      correct evaluation of its degree, based on recent different non-invasive
      procedures, is of current major concern. The latest methodology for assessing it
      is the Fibroscan and the effect of its employment is impressive. However, the
      complex interaction between its stiffness indicator and the other biochemical and
      clinical examinations towards a respective degree of liver fibrosis is hard to be
      manually discovered. In this respect, the novel, well-performing evolutionary
      powered support vector machines are proposed towards an automated learning of the
      relationship between medical attributes and fibrosis levels. The traditional
      support vector machines have been an often choice for addressing hepatic
      fibrosis, while the evolutionary option has been validated on many real-world
      tasks and proven flexibility and good performance. METHODS AND MATERIALS: The
      evolutionary approach is simple and direct, resulting from the hybridization of
      the learning component within support vector machines and the optimization engine
      of evolutionary algorithms. It discovers the optimal coefficients of surfaces
      that separate instances of distinct classes. Apart from a detached manner of
      establishing the fibrosis degree for new cases, a resulting formula also offers
      insight upon the correspondence between the medical factors and the respective
      outcome. What is more, a feature selection genetic algorithm can be further
      embedded into the method structure, in order to dynamically concentrate search
      only on the most relevant attributes. The data set refers 722 patients with
      chronic hepatitis C infection and 24 indicators. The five possible degrees of
      fibrosis range from F0 (no fibrosis) to F4 (cirrhosis). RESULTS: Since the
      standard support vector machines are among the most frequently used methods in
      recent artificial intelligence studies for hepatic fibrosis staging, the
      evolutionary method is viewed in comparison to the traditional one. The
      multifaceted discrimination into all five degrees of fibrosis and the slightly
      less difficult common separation into solely three related stages are both
      investigated. The resulting performance proves the superiority over the standard
      support vector classification and the attained formula is helpful in providing an
      immediate calculation of the liver stage for new cases, while establishing the
      presence/absence and comprehending the weight of each medical factor with respect
      to a certain fibrosis level. CONCLUSION: The use of the evolutionary technique
      for fibrosis degree prediction triggers simplicity and offers a direct expression
      of the influence of dynamically selected indicators on the corresponding stage.
      Perhaps most importantly, it significantly surpasses the classical support vector
      machines, which are both widely used and technically sound. All these therefore
      confirm the promise of the new methodology towards a dependable support within
      the medical decision-making.

PMID- 20675107
TI  - Red meat consumption and risk of heart failure in male physicians.
AB  - BACKGROUND AND AIMS: Heart failure (HF) remains a major public health issue. Red
      meat and dietary heme iron have been associated with an increased risk of
      coronary heart disease and hypertension, two major risk factors for HF. However,
      it is not known whether red meat intake influences the risk of HF. We therefore
      examined the association between red meat consumption and incident HF. METHODS
      AND RESULTS: We prospectively studied 21,120 apparently healthy men (mean age
      54.6 y) from the Physicians' Health Study (1982-2008). Red meat was assessed by
      an abbreviated food questionnaire and incident HF was ascertained through annual
      follow-up questionnaires. We used Cox proportional hazard models to estimate
      hazard ratios. In a multivariable model, there was a positive and graded relation
      between red meat consumption and HF [hazard ratio (95% CI) of 1.0 (reference),
      1.02 (0.85-1.22), 1.08 (0.90-1.30), 1.17 (0.97-1.41), and 1.24 (1.03-1.48) from
      the lowest to the highest quintile of red meat, respectively (p for trend
      0.007)]. This association was observed for HF with (p for trend 0.035) and
      without (p for trend 0.038) antecedent myocardial infarction. CONCLUSION: Our
      data suggest that higher intake of red meat is associated with an increased risk
      of HF.

PMID- 20675108
TI  - Atherogenic dyslipidemia in patients with established coronary artery disease.
AB  - BACKGROUND AND AIMS: Patients with stable coronary heart disease (CHD) and
      atherogenic dyslipidemia (AD) have a high-risk of recurrence and are those who
      derive most benefit from treatment with lipid-lowering agents. The aim of this
      study was to examine the prevalence of AD in patients with stable coronary heart
      disease and to investigate associated factors. METHODS: Cross-sectional study
      involving 7823 subjects admitted for a coronary event between 6 months and 10
      years previously. AD was considered to be the concurrent presence of low HDL
      cholesterol (<1.03 mmol/L [40 mg/dL] in males, <1.29 mmol/L [50 mg/dL] in
      females) and elevated triglycerides (>=1.7 mmol/L [150 mg/dL]). RESULTS: Mean age
      was 65.3 (10.1) years, 73.6% were males and 80.3% were receiving treatment with
      statins. Low HDL-cholesterol was observed in 26.3% of the participants, 39.7% had
      elevated triglyceride concentration and 13.0% had AD. The percentage of AD in
      patients with criteria for metabolic syndrome was 30.9%. Factors associated
      directly and independently with the presence of AD in the multivariate analysis
      were female sex, history of coronary syndrome without ST elevation or coronary
      revascularization, presence of atrial fibrillation, body mass index, LDL
      cholesterol, systolic blood pressure and blood glucose levels, while age and
      glomerular filtration rate were significantly and inversely associated with AD.
      CONCLUSION: A significant proportion of patients with coronary disease could
      benefit from interventions aimed at increasing HDL-cholesterol and reducing
      triglycerides.

PMID- 20675109
TI  - Early development of essential fatty acid deficiency in rats: fat-free vs.
      hydrogenated coconut oil diet.
AB  - This study examined the effects of feeding an essential fatty acid deficient
      (EFAD) diet either without fat or with added hydrogenated coconut oil (HCO) on
      fatty acid profiles in rats. Both diets induced equivalent biochemical evidence
      of EFAD reflected by the triene/tetraene ratio in plasma phospholipids within 2
      weeks. However, the HCO diet led to larger increases of 16:1n7 and 18:1n9 in
      muscle but smaller increases in fat tissue and plasma triglycerides than the fat
      free diet, suggesting greater increases in hepatic de novo lipogenesis with the
      latter. In addition, the HCO diet led to larger decreases of some 18:3n3
      metabolites, particularly 22:6n3, in muscle, fat and brain tissues than the fat
      free diet, presumably related to lesser stimulation of elongation and
      desaturation. Thus, these secondary effects of an EFAD diet on fatty acid
      metabolism can be modified by the saturated fat in the diet while the primary
      impact of both diets on development of EFAD is unaffected.

PMID- 20675110
TI  - A retrospective analysis of practice patterns in the management of acute asthma
      attack across Turkey.
AB  - OBJECTIVE: To evaluate patient characteristics and practice patterns in the
      management of acute asthma attack at tertiary care centers across Turkey.
      METHODS: A total of 294 patients (mean age: 50.4 +/- 15.1 years; females: 80.3%)
      diagnosed with persistent asthma were included in this retrospective study upon
      their admission to the hospital with an acute asthma attack. Patient
      demographics, asthma control level, asthma attack severity and the management of
      the attack were evaluated. RESULTS: There was no influence of gender on asthma
      control and attack severity. In 57.5% of the patients, asthma attack was
      moderate. Most patients (78.9%) were hospitalized with longer duration evident in
      the severe attack. Spirometry and chest X-Ray were the most frequent tests
      (85.4%), while steroids (72.0% parenteral; 29.0% oral) and short-acting beta
      agonists (SABA) + anticholinergics (45.5%) were the main drugs of choice in the
      attack management. Attack severity and pre-attack asthma control level was
      significantly correlated (p < 0.001). Pre-attack asthma was uncontrolled in 42.6%
      of the patients with severe attack. Most of the patients were on combination of
      more than one (two in 38.7% and 3-4 in 31.2%) controller drugs before the attack.
      CONCLUSION: Providing country specific data on practice patterns in the
      management of acute asthma attack in a representative cohort in Turkey,
      prescription of steroids and SABA + anticholinergics as the main drugs of choice
      was in line with guidelines while the significant relation of pre-attack asthma
      control to risk/severity of asthma attack and rate/duration of hospitalization
      seem to be the leading results of the present study.

PMID- 20675111
TI  - Epigenomics of centromere assembly and function.
AB  - The centromere is a complex chromosomal locus where the kinetochore is formed and
      microtubules attach during cell division. Centromere identity involves both
      genomic and sequence-independent (epigenetic) mechanisms. Current models for how
      centromeres are formed and, conversely, turned off have emerged from studies of
      unusual or engineered chromosomes, such as neocentromeres, artificial
      chromosomes, and dicentric chromosomes. Recent studies have highlighted the
      importance of unique chromatin marked by the histone H3 variant CENP-A, classical
      chromatin (heterochromatin and euchromatin), and transcription during centromere
      activation and inactivation. These advances have deepened our view of what
      defines a centromere and how it behaves in various genomic and chromatin
      contexts.

PMID- 20675112
TI  - Cohesin ties up the genome.
AB  - Cohesin was originally identified as a mediator of sister chromatid cohesion both
      in mitosis and meiosis. Emerging evidences suggest that it also participates in
      the organization of interphase chromatin. The ring-shaped complex regulates gene
      expression by constraining chromatin topology in concert with factors such as the
      insulator CTCF, at least in certain loci. The global relevance of this function
      of cohesin remains to be assessed, but its contribution to the pathology of the
      Cornelia de Lange syndrome seems evident. Our current knowledge of the molecular
      mechanisms underlying cohesin behavior should now be considered from the
      perspective of its novel functions, which promise to be as relevant for cell
      viability as cohesion.

PMID- 20675113
TI  - Trends in the use of Fenton, electro-Fenton and photo-Fenton for the treatment of
      landfill leachate.
AB  - Advanced oxidation processes (AOPs) such as Fenton, electro-Fenton and photo
      Fenton have been applied effectively to remove refractory organics from landfill
      leachate. The Fenton reaction is based on the addition of hydrogen peroxide to
      the wastewater or leachate in the presence of ferrous salt as a catalyst. The use
      of this technique has proved to be one of the best compromises for landfill
      leachate treatment because of its environmental and economical advantages. Fenton
      process has been used successfully to mineralize wide range of organic
      constituents present in landfill leachate particularly those recalcitrant to
      biological degradation. The present study reviews the use of Fenton and related
      processes in terms of their increased application to landfill leachate. The
      effects of various operating parameters and their optimum ranges for maximum COD
      and color removal are reviewed with the conclusion that the Fenton and related
      processes are effective and competitive with other technologies for degradation
      of both raw and pre-treated landfill leachate.

PMID- 20675114
TI  - Controlled combustion tests and bottom ash analysis using household waste with
      varying composition.
AB  - The influence of the co-combustion of household waste with either sewage sludge,
      shredder fluff, electronic and electrical waste (WEEE) or PVC on the bottom ash
      quality and content was investigated under controlled laboratory conditions using
      a pot furnace. This laboratory approach avoids the interpretation problems
      related to large variations in input waste composition and combustion conditions
      that are observed in large scale MSW incinerators. The data for metals content,
      transfer coefficients and leaching values are presented relative to data for a
      base household waste composition that did not contain any of the added special
      wastes. The small WEEE invited direct measurement of precious metals content in
      the ashes, where measurement accuracy is facilitated by using only mobile phone
      scrap for small WEEE. The analyses were carried out for different particle size
      ranges that are of relevance to the recyclability of metals and minerals in the
      ashes. Positive correlations were found between elements content of the input
      waste and the bottom ashes, and also between increased levels of Cl, Mo and Cu in
      the input waste and their leaching in the bottom ashes. These correlations
      indicate that addition of PVC, small WEEE and shredder fluff in input waste can
      have a negative influence on the quality of the bottom ashes. Enrichment of Au
      and Ag occurred in the fractions between 0.15 and 6 mm. The precious metals
      content represents an economically interesting intrinsic value, even when the
      observed peak values are properly averaged over a larger volume of ashes.
      Overall, it has been shown that changes in quality and content of bottom ashes
      may be traced back to the varied input waste composition.

PMID- 20675115
TI  - Continuous-feeding vermicomposting as a recycling management method to revalue
      tomato-fruit wastes from greenhouse crops.
AB  - Huge quantities of discarded fruits generated from greenhouse crops represent a
      worldwide environmental problem. The aim of this work was to assess the
      efficiency of vermicomposting as a recycling management option for
      biotransforming tomato-fruit wastes from greenhouses into an organic nutrient
      rich product available for agricultural purposes. A pilot vermireactor was
      constructed. It was provided with a manure layer, where an initial population of
      Eisenia fetida was introduced and fed continuously at a high organic loading rate
      (13.6 kg TOC m(-3)wk(-1)) for 150 days. Vermicompost chemical and enzymatic
      parameters as well as the bacterial and fungal community structure were
      determined for 210 days (vermicomposting plus a maturation period). Earthworm
      biomass increased after 90 days, and then declined due to increasing pH,
      electrical conductivity and ammonium concentration. The temporal patterns of
      dehydrogenase, beta-glucosidase, protease and urease were related to earthworm
      growth and the stabilization of organic matter. Bacterial DGGE profiles differed
      between the period of degradation of labile substrates and the maturation step.
      Fungal communities at the stage of maximum earthworm biomass differed most,
      suggesting a gut passage effect. The end product was chemically stable and
      enriched in nutrients, demonstrating that tomato-fruit wastes can be successfully
      vermicomposted into a valuable soil amendment. We suggest continuous-feeding
      vermicomposting as an environmentally sound management option for greenhouse
      wastes.

PMID- 20675116
TI  - Label-free optical biosensor based on localized surface plasmon resonance of twin
      linked gold nanoparticles electrodeposited on ITO glass.
AB  - A simple low-cost electrochemical approach has been used to directly deposit twin
      linked gold nanoparticles (TGNPs) onto transparent indium tin oxide (ITO) coated
      film glass. The as-prepared TGNPs have a transverse localized surface plasmon
      resonance (LSPR) band at 540 nm and a longitudinal LSPR band at about 710 nm. The
      longitudinal LSPR band of TGNPs exhibits higher refractive index sensitivity (245
      nm/RIU) than its transverse LSPR band. The resulting "clean" surface of the TGNPs
      is easy applied to the further modification. The subsequent bioconjugation of
      TGNP films with goat anti-mouse-immunoglobulin G (anti-m-IgG) is successfully
      employed for the detection of mouse-immunoglobulin G (m-IgG) in a model based on
      the specific binding affinity between the antigen and antibody. The
      spectrophotometric sensor shows concentration-dependent binding for m-IgG. This
      study reveals a simple and sensitive method to fabricate a label-free optical
      biosensor based on longitudinal LSPR band of TGNPs on ITO substrate.

PMID- 20675117
TI  - A gold nanorod-based optical DNA biosensor for the diagnosis of pathogens.
AB  - A novel optical biosensor for detecting target DNA, utilizing gold nanorods
      (GNRs) as molecular probes is demonstrated. This sensor is based on simultaneous
      biorecognition-mediated hybridization of target DNA in a sandwich type manner
      with two different capture probe DNA sequences modified separately with identical
      sets of GNRs, which leads to aggregation of GNRs. The hybridization induced
      aggregation as revealed by TEM analysis, promotes the modulation of surface
      plasmon resonance of GNRs, which forms the basis of complementary target DNA
      detection from the Chlamydia trachomatis pathogen. Thermally induced reversible
      dissociation of hybridized DNA is demonstrated by melting analysis. The present
      sensing strategy is successfully demonstrated by detecting PCR amplified C.
      trachomatis pathogen gene isolated from human urine sample in a concentration
      range of 0.25-20 nM. Furthermore, this sensor displays excellent specificity by
      discriminating the target DNA versus other non-specific pathogenic genes.

PMID- 20675118
TI  - Optical fiber sensor for Hg(II) based on carbon dots.
AB  - An optical fiber sensor for Hg(II) in aqueous solution based on sol-gel
      immobilized carbon dots nanoparticles functionalized with PEG(200) and N-acetyl-L
      cysteine is described. This sol-gel method generated a thin (about 750 nm),
      homogenous and smooth (roughness of 2.7+/-0.7 A) film that immobilizes the carbon
      dots and allows reversible sensing of Hg(II) in aqueous solution. A fast (less
      than 10 s), reversible and stable (the fluorescence intensity measurements
      oscillate less than 1% after several calibration cycles) sensor system was
      obtained. The sensor allow the detection of submicron molar concentrations of
      Hg(II) in aqueous solution. The fluorescence intensity of the immobilized carbon
      dots is quenched by the presence of Hg(II) with a Stern-Volmer constant (pH=6.8)
      of 5.3*10(5) M(-1).

PMID- 20675119
TI  - Performing enzyme-free H2O2 biosensor and simultaneous determination for AA, DA,
      and UA by MWCNT-PEDOT film.
AB  - An enzyme-free hydrogen peroxide (H2O2) biosensor based on MWCNT-PEDOT film
      modified electrode has been successfully performed on glassy carbon electrode
      (GCE) and indium tin oxide (ITO) electrode. At an applied potential of -0.5V vs.
      Ag/AgCl, the MWCNT-PEDOT electrode exhibited linearly dependence on H2O2
      concentration in the range of 0.1-9.8 mM. It can be observed two significantly
      linear sections. One shows sensitivity of 943 MUM mM(-1) cm(-2) with signal/noise
      of 6; and the other one shows sensitivity of 174 MUM mM(-1) cm(-2) with
      signal/noise of 4 in pH 7 PBS. It also presented excellent stability at room
      temperature, with a variation of response current less than 5% over 30 days.
      Moreover, the sensor was characterized by cyclic voltammetry (CV), scanning
      electronic microscopy (SEM), atomic force microscopy (AFM), and different pulse
      voltammetry (DPV). This sensor also can simultaneously detect AA, DA, and UA and
      can be utilized to develop multifunctional biosensors.

PMID- 20675120
TI  - Quality indicators in breast cancer care.
AB  - To define a set of quality indicators that should be routinely measured and
      evaluated to confirm that the clinical outcome reaches the requested standards,
      Eusoma has organised a workshop during which twenty four experts from different
      disciplines have reviewed the international literature and selected the main
      process and outcome indicators available for quality assurance of breast cancer
      care. A review of the literature for evidence-based recommendations have been
      performed by the steering committee. The experts have identified the quality
      indicators also taking into account the usability and feasibility. For each of
      them it has been reported: definition, minimum and target standard, motivation
      for selection and level of evidence (graded according to AHRO). In overall 17
      main quality indicators have been identified, respectively, 7 on diagnosis, 4 on
      surgery and loco-regional treatment, 2 on systemic treatment and 4 on staging,
      counselling, follow-up and rehabilitation. Breast Units in Europe are invited to
      comply with these indicators and monitor them during their periodic audit
      meetings.

PMID- 20675121
TI  - Occurrence of other tumors in patients with GIST.
AB  - OBJECTIVE: Evaluate the presence of other tumors in cohort of patients with GIST
      treated at a cancer treatment referral center - INCA. METHODS: We reviewed the
      medical records of patients diagnosed with GIST who were treated at INCA between
      1998 and 2008. Immunohistological diagnosis was confirmed by a pathologist
      specialized in sarcomas. Patients presenting second non-GIST tumors were
      identified. Age, sex, tumor location, risk groups (according to the National
      Institutes of Health criteria), characteristics of non-GIST tumors and treatment
      results were analyzed. RESULTS: Among the 101 patients diagnosed with GIST who
      were evaluated during the study period, 14 (13.8%) had other non-GIST tumors, 9
      females (64.3%), with a median age of 68 years (10-79 years). The stomach was the
      location of GISTs in 8 cases (57.1%), followed by the small bowel in 4 cases
      (28.5%), colon and mesentery with 1 case (7.1%) each. The mean size of lesions
      was 4.79 cm (0.3-15 cm), with malignant potential low/very low in 7 cases (50%),
      intermediate in 5 cases (35.7%) and high in 2 cases (14.3%). The diagnosis of
      GIST was incidental in 6 cases and in one case the non-GIST tumor was incidental.
      The non-GIST tumors were most frequent in the stomach (adenocarcinoma), in 4
      cases (28.5%) and colon/rectum (adenocarcinoma) in 4 other cases. The other sites
      involved were breast (ductal carcinoma), kidney (clear cell carcinoma), prostate
      (adenocarcinoma), endometrium (adenocarcinoma), ovary (adenocarcinoma) and
      adrenal (neuroblastoma), with one case each. The tumors were synchronous in 7
      cases (50%). With a median follow-up after GIST resection of 41 months (2-87
      months), 9 patients were alive without evidence of disease, 2 died due to GIST, 2
      died due to non-GIST tumors and the remaining patient died due to postoperative
      complications. CONCLUSIONS: We discovered a 13.8% incidence of non-GIST tumors in
      a series of 101 GIST cases under our care. This association should always be
      considered in the management of patients with GIST.

PMID- 20675122
TI  - Manipulating the molecular weight of alginate produced by Azotobacter vinelandii
      in continuous cultures.
AB  - Alginate production by Azotobacter vinelandii in chemostat cultures was evaluated
      at different dilution rates (D) and inlet sucrose concentrations of 5 and 20 g l(
      1). At the low inlet sucrose concentration, the molecular weight of alginate
      increased from 800 to 1800 kDa when D increased from 0.05 to 0.10 h(-1), whereas
      the opposite trend was observed with the high inlet sucrose concentration. This
      behaviour can be explained by changes in specific sucrose uptake rate. Thus, a
      decrease in alginate molecular weight was dependent on the specific sucrose
      uptake rate when this rate was higher than 0.42 g g(-1) h(-1). The manipulation
      of the D can be used to select the molecular weight of alginate in continuous
      culture.

PMID- 20675123
TI  - Dispersed ozone flotation of Chlorella vulgaris.
AB  - Flotation separation of Chlorella vulgaris, a species with excellent potential
      for CO(2) capture and lipid production, was studied using dispersed ozone gas.
      Pure oxygen aeration did not yield flotation. Conversely, applying ozone
      effectively separation algae from broth through flotation. The ozone dose applied
      for sufficient algal flotation is <0.05 mg/g biomass, much lower than those used
      in practical drinking waterworks (0.1-0.3 mg/g suspended solids). Main products,
      lipid C16:0, was effectively collected in the flotage phase. The algae removal
      rate, surface charge, and hydrophobicity of algal cells, and proteins and
      polysaccharides contents of algogenic organic matter (AOM) were determined.
      Certain quantities of proteins were present in the cultivated algal suspension,
      hence, minimal quantity of ozone was required to release intracellular proteins
      as surfactants to lead to effective flotation.

PMID- 20675124
TI  - Production of lignocellulolytic enzymes and enhancement of in vitro digestibility
      during solid state fermentation of wheat straw by Phlebia floridensis.
AB  - Degradation by white rot fungi has the potential to increase digestibility of
      wheat straw and thus improve its value as animal feed. To optimize conditions for
      production of lignocellulolytic enzymes by Phlebia floridensis during solid state
      fermentation of wheat straw along with enhancement of in vitro digestibility, a
      response surface methodology (RSM) based experiment was designed. Effect of
      moisture content, inorganic nitrogen source (NH(4)Cl) and malt extract on
      lignocellulolytic enzymes, changes in chemical constituents and digestibility of
      wheat straw was evaluated. With increase in moisture content, laccase production
      increased up to 34-fold, while Manganese peroxidase was optimally produced in the
      presence of almost equal amount (50-55 mg/g of WS) of NH(4)Cl and malt extract.
      These supplements also significantly (p<0.05) enhanced the production of CMCase
      and xylanase. In vitro digestibility was increased by almost 50% with a loss of
      27.6% and 14.6% in lignin and total organic matter, respectively. The present
      findings revealed P. floridensis to be an efficient organism for
      lignocellulolytic enzymes production and simultaneous enhancement in in vitro
      digestibility of wheat straw.

PMID- 20675125
TI  - Life-cycle analysis on biodiesel production from microalgae: water footprint and
      nutrients balance.
AB  - This research examines the life-cycle water and nutrients usage of microalgae
      based biodiesel production. The influence of water types, operation with and
      without recycling, algal species, geographic distributions are analyzed. The
      results confirm the competitiveness of microalgae-based biofuels and highlight
      the necessity of recycling harvested water and using sea/wastewater as water
      source. To generate 1 kg biodiesel, 3726 kg water, 0.33 kg nitrogen, and 0.71 kg
      phosphate are required if freshwater used without recycling. Recycling harvest
      water reduces the water and nutrients usage by 84% and 55%. Using sea/wastewater
      decreases 90% water requirement and eliminates the need of all the nutrients
      except phosphate. The variation in microalgae species and geographic distribution
      are analyzed to reflect microalgae biofuel development in the US. The impacts of
      current federal and state renewable energy programs are also discussed to suggest
      suitable microalgae biofuel implementation pathways and identify potential
      bottlenecks.

PMID- 20675126
TI  - Drawida willsi Michalsen activates cellulolysis in pressmud vermireactor.
AB  - In the present study, the role of earthworm species Drawida willsi Michalsen in
      cellulose decomposition of microbial rich pressmud substrate has been evaluated,
      and to assess whether this native species of earthworm digest cellulose directly
      (with associated gut microbiota) and also to know if there is any effect on
      microbial biomass and activity leading to a change in the equilibrium between
      fungi and bacteria during decomposition process. The findings suggest that the
      presence or absence of earthworms in vermireactors significantly increased the
      rate of cellulose decomposition (0.43 and 0.26% cellulose loss day(-1) with and
      without earthworms, respectively). However, the direct contribution of D. willsi
      to degradation of cellulose was not significant; although the presence of
      earthworms considerably increased microbial biomass and cellulase and beta
      glucosidase activity.

PMID- 20675127
TI  - Systematic investigation of biomass and lipid productivity by microalgae in
      photobioreactors for biodiesel application.
AB  - We describe a methodology to investigate the potential of given microalgae
      species for biodiesel production by characterizing their productivity in terms of
      both biomass and lipids. A multi-step approach was used: determination of
      biological needs for macronutrients (nitrate, phosphate and sulphate),
      determination of maximum biomass productivity (the "light-limited" regime),
      scaling-up of biomass production in photobioreactors, including a theoretical
      framework to predict corresponding productivities, and investigation of how
      nitrate starvation protocol affects cell biochemical composition and triggers
      triacylglycerol (TAG) accumulation. The methodology was applied to two freshwater
      strains, Chlorella vulgaris and Neochloris oleoabundans, and one seawater diatom
      strain, Cylindrotheca closterium. The highest total lipid content was achieved
      with N. oleoabundans (25-37% of DW), while the highest TAG content was found in
      C. vulgaris (11-14% of DW). These two species showed similar TAG productivities.

PMID- 20675128
TI  - Serratia sp. ZF03: an efficient radium biosorbent isolated from hot-spring waters
      in high background radiation areas.
AB  - The aim of this study is to isolate and characterize (226)Ra biosorbing
      indigenous bacterial strains from soils and hot-springs containing high
      concentrations of (226)Ra by using biochemical and molecular approaches. Fifteen
      bacteria were isolated and their phylogenetic affiliations were determined based
      on their 16S rRNA gene and the two most relevant hypervariable regions of this
      gene; V3 and V6 analysis. A pigmented Serratia sp. ZF03 strain isolated from the
      water with (226)Ra content of 50471 mBq l(-1), caused 70% removal of (226)Ra at a
      radioactivity level of 50 Bq ml(-1), after 5 min and 75-80% in equilibrium time
      of 1 h, depending on the particular biosorption system and experimental
      conditions studied. The biosorption equilibrium was described by Langmuir and
      Freundlich isotherm models. Kinetic studies indicated that the biosorption
      follows pseudo-second-order kinetics. Effect of different physico-chemical
      parameters on (226)Ra sorption, FTIR, SEM and TEM analysis were also
      investigated.

PMID- 20675129
TI  - The feasibility study of crude palm oil transesterification at 30  degrees C
      operation.
AB  - The objective of this research is to investigate the potential of
      transesterification of crude palm oil (CPO) to biodiesel at 30 degrees C. The
      mass transfer limitations problem crucial at 30 degrees C due to the viscosity of
      CPO has been addressed. The process parameters that are closely related to mass
      transfer effects like enzyme loading, agitation speed and reaction time were
      optimized. An optimum methanol to oil substrate molar ratio at 6.5:1 was observed
      and maintained throughout the experiments. The optimum operating condition for
      the transesterification process was found at 6.67 wt% of enzyme loading and at
      150 rpm of agitation speed. The corresponding initial reaction and FAME yield
      obtained at 6 h were 89.29% FAME yield/hr and 85.01%, respectively. The 85% FAME
      yield obtained at 30 degrees C operation of CPO transesterification shows that
      the process is potentially feasible for the biodiesel synthesis.

PMID- 20675130
TI  - InCl3 mediated one-pot multicomponent synthesis, anti-microbial, antioxidant and
      anticancer evaluation of 3-pyranyl indole derivatives.
AB  - A simple and convenient method for the one-pot three-component synthesis of 3
      pyranyl indoles has been accomplished by tandem Knoevenagel-Michael reaction of 3
      cyanoacetyl indole, various aromatic aldehydes and malononitrile catalyzed by
      InCl(3) in ethanol under reflux conditions. The newly synthesized 3-pyranyl
      indoles were evaluated for anti-microbial, antioxidant, and anticancer
      activities. Some of the compounds showed good anticancer activity against MCF-7
      breast cancer cell lines on comparison with of standard drug.

PMID- 20675131
TI  - Unnatural enantiomer of chaetocin shows strong apoptosis-inducing activity
      through caspase-8/caspase-3 activation.
AB  - Chaetocin, a natural product isolated from Chaetomium species fungi, was reported
      to have various biological activities, including antitumor and antifungal
      activities. Recently, we reported the first total synthesis of chaetocin and its
      derivatives. Here, we examined the cell-death-inducing activity of these
      compounds in human leukemia HL-60 cells. The unnatural enantiomer of chaetocin
      (ent-chaetocin) was more potent than chaetocin, and was found to induce apoptosis
      through the caspase-8/caspase-3 activation pathway.

PMID- 20675132
TI  - Synthesis and biochemical evaluation of a range of (4-substituted
      phenyl)sulfonate derivatives of 4-hydroxybenzyl imidazole-based compounds as
      potent inhibitors of 17alpha-hydroxylase/17,20-lyase (P45017alpha) derived from
      rat testicular microsomes.
AB  - We report the synthesis, biochemical evaluation and rationalisation of the
      inhibitory activity of a range of (4-substituted phenyl)sulfonate derivatives of
      4-hydroxybenzyl imidazole against the two components of 17alpha-hydroxylase/17,20
      lyase (P450(17alpha)), namely, 17alpha-hydroxylase (17alpha-OHase) and 17,20
      lyase (lyase). The results show the compounds to be highly potent inhibitors with
      limited selectivity towards the lyase component [e.g., toluene-4-sulfonic acid 4
      imidazol-1-ylmethyl-phenyl ester (4) possessed an IC(50) value of 40 nM against
      17alpha-OHase and 30 nM against lyase].

PMID- 20675133
TI  - SAR studies of non-zinc-chelating MMP-13 inhibitors: improving selectivity and
      metabolic stability.
AB  - SAR studies to improve the selectivity and metabolic stability of a class of
      recently discovered MMP-13 inhibitors are reported. Improved selectivity was
      achieved by modifying interactions with the S1' pocket. Metabolic stability was
      improved through reduction of inhibitor lipophilicity. This translated into lower
      in vivo clearance for the preferred compound.

PMID- 20675134
TI  - Discovery of imidazo[1,2-b]pyridazine derivatives as IKKbeta inhibitors. Part 1:
      Hit-to-lead study and structure-activity relationship.
AB  - Imidazo[1,2-b]pyridazine derivatives from high-throughput screening were
      developed as IKKbeta inhibitors. By the optimization of the 3- and 6-position of
      imidazo[1,2-b]pyridazine scaffold, cell-free IKKbeta inhibitory activity and
      TNFalpha inhibitory activity in THP-1 cell increased. Also, these compounds
      showed high kinase selectivity. The structure-activity relationship was revealed
      and the interaction model of imidazo[1,2-b]pyridazine compounds with IKKbeta was
      constructed.

PMID- 20675135
TI  - Preparation of classical Re/99mTc(CO)3(+) and novel 99mTc(CO)2(NO)2+ cores
      complexed with flavonol derivatives and their binding characteristics for Abeta(1
      40) aggregates.
AB  - Classical (99m)Tc(CO)(3)(+) and novel (99m)Tc(CO)(2)(NO)(2+) cores complexed with
      flavonol derivatives were prepared. Autoradiography of postmortem AD transgenic
      mice (Tg C57, APP, PS1 12-month-old) brain section confirmed the binding property
      of [(99m)Tc(CO)(3)(+)-3-OH-flavone](0) to Abeta((1-40)) aggregates, while the
      novel (99m)Tc(CO)(2)(NO)(2+) labeled compounds showed no binding sites in AD
      transgenic mice sections. Intravenous administration of [(99m)Tc(CO)(3)(+)-3-OH
      flavone](0) resulted in moderate brain uptake (0.48+/-0.05%ID/g) at 5 min post
      injection and slow clearance from the brain issues in 2h post-injection (120 min:
      0.39+/-0.08%ID/g). Then an Abeta((1-40))-receptor-targeted Re(CO)(3)(+)-3-OH
      flavone, was prepared to identify the structure of the technetium complex. UV-vis
      absorption and fluorescence emission properties have been studied at room
      temperature in order to determine the natures of the lowest electronically
      excited states of Re(CO)(3)(+)-3-OH-flavone and the ligand. The fluorescent
      rhenium complex Re(CO)(3)(+)-3-OH-flavone showed high affinity for Abeta((1-40))
      aggregates in vitro by fluorescence spectra (dissociation constant (K(d))=11.16
      nM). In conclusion, the results suggested that (99m)Tc(CO)(3)(+)-3-OH-flavone
      should be a suitable candidate as Abeta plaque SPECT imaging agent for AD.

PMID- 20675136
TI  - Synthesis and biological evaluation of oxoindolin-3-ylidene ethyl
      benzothiohydrazides as non-peptide TPO mimics.
AB  - A novel series of oxoindolin-3-ylidene ethyl benzohydrazides were designed,
      synthesized, and identified as small molecule agonists of thrombopoietin (TPO)
      receptor c-mpl. Sulfur-oxygen exchange in oxoindolin-3-ylidene ethyl
      benzohydrazides was found to improve their agonistic activities. Several
      oxoindolin-3-ylidene ethyl benzothiohydrazides have been identified as full
      agonists of c-mpl.

PMID- 20675137
TI  - Proline isosteres in a series of 2,4-disubstituted pyrrolo[1,2-f][1,2,4]triazine
      inhibitors of IGF-1R kinase and IR kinase.
AB  - Pyrrolidine, pyrrolidinone, carbocyclic, and acyclic groups were used as
      isosteric proline replacements in a series of insulin-like growth factor I
      receptor kinase/insulin receptor kinase inhibitors. Examples that were similar in
      potency to proline-containing reference compounds were shown to project a key
      fluoropyridine amide into a common space, while less potent compounds were not
      able to do so for reasons of stereochemistry or structural rigidity.

PMID- 20675138
TI  - Synthesis and evaluation of oryzalin analogs against Toxoplasma gondii.
AB  - The synthesis and evaluation of 20 dinitroanilines and related compounds against
      the obligate intracellular parasite Toxoplasma gondii is reported. Using in vitro
      cultures of parasites in human fibroblasts, we determined that most of these
      compounds selectively disrupted Toxoplasma microtubules, and several displayed
      sub-micromolar potency against the parasite. The most potent compound was
      N(1),N(1)-dipropyl-2,6-dinitro-4-(trifluoromethyl)-1,3-benzenediamine (18b),
      which displayed an IC(50) value of 36 nM against intracellular T. gondii. Based
      on these data and another recent report [Ma, C.; Tran, J.; Gu, F.; Ochoa, R.; Li,
      C.; Sept, D.; Werbovetz, K.; Morrissette, N. Antimicrob. Agents Chemother. 2010,
      54, 1453], an antimitotic structure-activity relationship for dinitroanilines
      versus Toxoplasma is presented.

PMID- 20675139
TI  - A stable analog of isochorismate for the study of MenD and other isochorismate
      utilizing enzymes.
AB  - A novel analog of isochorismate, in which the enolpyruvyl substituent is replaced
      with a carboxymethoxyl group, has been synthesized in four steps from a known
      intermediate. This analog is more stable than the natural product, but still acts
      as a good substrate for the enzyme MenD (SEPHCHC synthase). The enzyme consumes
      the (+)-enantiomer only, with an apparent turnover similar to that of the natural
      substrate, and an apparent Michaelis constant conveniently higher than that of
      isochorismate. This analog will be useful in the study of any isochorismate
      utilizing enzyme.

PMID- 20675140
TI  - Evaluation of HER2/neu oncoprotein in serum and tissue samples of women with
      breast cancer: correlation with clinicopathological parameters.
AB  - BACKGROUND: HER2/neu (HER2) is a proto-oncogen of the EGF Receptor family. The
      assessment of serum HER2 level is useful for predicting the patients' response to
      chemotherapy or hormonal therapy and selection of proper patients for treatment
      with Herceptin. We aimed to compare serum HER2 levels with immunohistochemistry
      in tumoral tissues and investigate correlation between these levels and various
      prognostic factors. MATERIALS AND METHODS: This cross-sectional study was
      conducted on 75 patients with breast carcinoma referred to surgical ward of
      Mashhad Imam Reza's hospital from November 2008 to February 2009. Pre-operative
      serum samples were collected and stored in -20 degrees C. Surgical samples were
      investigated for the type of carcinoma, tumor size, lymph node metastasis, stage
      as well as grade of the tumor. Tissue HER2 over-expression was evaluated by
      immunohistochemistry (IHC) staining and HER2 levels were studied by ELISA method.
      Statistical analysis was performed by SPSS software. RESULTS: Serum HER2 cut-off
      level was 18.4 ng/ml; 46.7% of patients were serum HER2-positive and 43% were IHC
      positive. There was a high statistical correlation between these two parameters
      (P=0.018). Statistically, there was no significant correlation between serum HER2
      and age, tumor size, stage, grade and metastatic lymph nodes (P>0.05).
      CONCLUSION: Serum HER2 level assay can be considered as a complementary method
      besides tissue methods.

PMID- 20675141
TI  - Bilateral stress fracture of the femoral shaft after total knee arthroplasty: a
      case report.
AB  - The authors present a case of bilateral stress fracture of the femoral shaft 15
      years after total knee arthroplasty. Considerable femoral bowing deformity and
      varus malposition of the femoral and tibial components after total knee
      arthroplasty may produce abnormal stresses and lead to stress fracture of the
      distal femur in the region of greatest curvature.

PMID- 20675142
TI  - Synthesis, activity, and pharmacokinetic properties of a series of
      conformationally-restricted thiourea analogs as novel hepatitis C virus
      inhibitors.
AB  - A series of novel conformationally-restricted thiourea analogs were designed,
      synthesized, and evaluated for their anti-HCV activity. Herein we report the
      synthesis, structure-activity relationships (SARs), and pharmacokinetic
      properties of this new class of thiourea compounds that showed potent inhibitory
      activities against HCV in the cell-based subgenomic HCV replicon assay. Among
      compounds tested, the fluorene compound 4b was found to possess the most potent
      activity (EC(50)=0.3 microM), lower cytotoxicity (CC(50)>50 microM), and
      significantly better pharmacokinetic properties compared to its corresponding
      fluorenone compound 4c.

PMID- 20675143
TI  - Small photoactivatable molecules for controlled fluorescence activation in living
      cells.
AB  - The search for chemical probes which allow a controlled fluorescence activation
      in living cells represent a major challenge in chemical biology. To be useful,
      such probes have to be specifically targeted to cellular proteins allowing
      thereof the analysis of dynamic aspects of this protein in its cellular
      environment. The present paper describes different methods which have been
      developed to control cellular fluorescence activation emphasizing the
      photochemical activation methods known to be orthogonal to most cellular
      components and, in addition, allowing a spatio-temporal controlled triggering of
      the fluorescent signal.

PMID- 20675144
TI  - Cytogenetic analysis of two Coprophanaeus species (Scarabaeidae) revealing wide
      constitutive heterochromatin variability and the largest number of 45S rDNA sites
      among Coleoptera.
AB  - The Coleopterans of Scarabaeinae clade presents Coprophanaeus (Megaphanaeus)
      ensifer and C. (Coprophanaeus) cyanescens (Scarabaeidae) when they are studied
      cytogenetically by different techniques. The species present symmetric
      karyotypes, diploid number of 2n=20, and meta-submetacentric chromosomes. C. (M.)
      ensifer present an XY sex-determining mechanism and C. (C.) cyanescens an XY(p)
      parachute mechanism. Analysis of constitutive heterochromatin (CH) in the two
      species revealed the presence of diphasic autosomes, with log arm
      heterochromatics. Moreover, an additional heterochromatic block in four autosomal
      bivalents were observed in C. (M.) ensifer. CMA(3)/DA/DAPI fluorochrome staining
      detected CMA(3) positive heterochromatic blocks restricted to the sex chromosomes
      in C. (C.) cyanescens, whereas in C. (M.) ensifer CMA(3) positive pericentromeric
      blocks were present in all autosomes, in the Y chromosome and in the four
      additional heterochromatic blocks. DAPI staining was neutral in both species.
      Silver nitrate (AgNO(3)) staining was inefficient for the detection of the
      nucleolar organizer region (NORs), but showed affinity for the heterochromatic
      regions. Fluorescence in situ hybridization (FISH) revealed the presence of 45S
      rDNA sites in the terminal region of the three autosomal bivalents of C. (C.)
      cyanescens and in seven bivalents and the Y chromosome of C. (M.) ensifer. These
      results contribute to a better understanding of chromosome evolution in the genus
      Coprophanaeus, and demonstrate a wide CH variability and the largest number of
      ribosomal sites among Coleoptera.

PMID- 20675145
TI  - Cryo-electron tomography on vitrified sections: a critical analysis of benefits
      and limitations for structural cell biology.
AB  - The technology to produce cryo-electron tomography on vitrified sections is now a
      few years old and some specialised labs worldwide have gathered sufficient
      experience so that it is justified at this point to critically analyse its
      usefulness for cellular and molecular biology, and make predictions on how the
      method might develop from here. Remarkably, the production of vitrified sections
      has been introduced some 40 years ago (the very origin dates back to Christensen,
      1971, and McDowall et al., 1983). However, the real breakthrough came between
      2002 and 2004 when the groups of Jacques Dubochet and Carmen Manella
      independently resurrected the vitrified sectioning technology from its sleeping
      beauty state. And despite its hooks and hurdles a beauty indeed it is! When
      aiming at the right subjects the results obtained by vitrified sectioning and
      soon after by cryo-electron tomography exceeded all expectations. Molecular
      details of intracellular structures were imaged with never before seen clarity in
      a comparable setting, and the structural preservation of macromolecular
      assemblies within cells was stunning. However, as with every progress, the great
      results we now have with vitrified sectioning come at a price. The sectioning
      procedure and handling of vitrified sections is tricky and requires substantial
      training and experience. Once frozen, the specimens cannot be manipulated anymore
      (e.g., by staining or immuno-labelling). The contrast, as with all true cryo-EM
      approaches, is produced solely by small density differences between cytosol and
      macromolecular assemblies, membranes, or nucleic acid structures (e.g.,
      ribosomes, nucleosomes, inner nuclear structures, etc.). Vitrified sectioning
      should not be seen as a competition to the more established plastic-section
      tomography, but constitutes an excellent complement, filling in high-resolution
      detail in the overview of cellular architecture. Here we critically compare the
      benefits and limitations of vitrified sectioning for its application to modern
      structural cell biology.

PMID- 20675146
TI  - Clinical indication for intraoperative 3D imaging during open reduction of
      fractures of the neck and head of the mandibular condyle.
AB  - PURPOSE: This study aimed to evaluate the use of intraoperative cone-beam
      computed tomography (CBCT) in monitoring the results of repositioning and
      osteosynthesis of condylar process and head (capitulum) fractures of the mandible
      to see if CBCT is beneficial for these patients. PATIENTS AND METHODS: Sixty
      patients (22 females and 38 males, age range 16-79 years, average 36.5 years)
      with condylar process and head fractures according to the classification of
      Spiessl and Schroll were treated during the study period. Thirty-four of the 60
      patients received a CBCT scan immediately after surgical treatment under aseptic
      conditions. RESULTS: In all 34 cases, intraoperative CBCT provided high-quality
      imaging of the condylar process in all three planes. In four patients (11.8%),
      unsatisfactory reposition or unexpected complications were detected which could
      immediately be corrected with a surgical revision. CONCLUSION: Intraoperative use
      of CBCT enables optimization of the surgical outcome for fractures of the
      condylar process and head of the mandible, reduces postoperative complications,
      and spares patients from repeated intervention. In addition, intraoperative CBCT
      enables safer treatment with minimally invasive approaches.

PMID- 20675147
TI  - How to use bleomycin A5 for infantile maxillofacial haemangiomas: clinical
      evaluation of 82 consecutive cases.
AB  - OBJECTIVE: Bleomycin A5 has been reported effective for infantile haemangioma
      (IH), but the usage and complications were described a little. We have used
      bleomycin A5 to treat maxillofacial IHs for 15 years. This paper describes the
      procedures to use bleomycin A5 and avoid its complications based on our clinical
      practices. METHODS: Bleomycin A5 (8mg, powder) was mixed with 2% lidocaine (3ml)
      and dexamethasone (1ml, 5mg), the mixture concentration is 2mg/ml (bleomycin A5).
      The drug was given by multiple intralesional injections, with the dosage
      calculated according to the age of the patient and size of the lesion. Cautions
      were paid to the drug dosage and concentration, as well as the depth of
      injection. The patients were also given oral prednisone (2-5mg/kg every other
      day) during proliferating stage. RESULTS: After treatment with bleomycin A5 in
      appropriate quantity and concentration, injecting depth, all haemangiomas
      involuted completely, with smaller lesions showing better recovery of skin colour
      and less scar formation, and no serious side effects happened. CONCLUSION:
      Bleomycin A5 is an effective treatment for IHs. Oral prednisone is necessary for
      patients at proliferating stage.

PMID- 20675148
TI  - An additional maneuver to repair mitral paravalvular leak.
AB  - Paravalvular leaks still occur following prosthetic valvular replacement. When
      the leaks are large or are causing symptoms or hemolysis, they require closure.
      Multiple techniques, including transcatheter interventions, are described in the
      literature to deal with the problem. This article describes a simple surgical
      technique that can secure closure of mitral paravalvular leaks in the vicinity of
      the coronary sinus.

PMID- 20675149
TI  - Video-assisted pericardioscopic surgery: refinement of a new technique for
      implanting epimyocardial pacemaker leads.
AB  - OBJECTIVE: Current alternative approaches for pacemaker lead implantation imply
      the breach of the pleural space. Recently, the feasibility of experimental lead
      implantation by rigid endoscopy has been described. The use of flexible
      endoscopes and a standardised application has not been realised yet. Our main
      goal was to compare rigid and flexible endoscopy and to establish a standardised
      protocol for the implementation of a closed-chest subxiphoid approach for
      epimyocardial lead implantation. METHODS: Rigid and flexible endoscopes were used
      for placement of screw-in pacing leads (4-F). A total of 17 adult pigs (80 kg)
      were anaesthetised and a 10-mm subxiphoid axial incision performed. The
      pericardium was opened and entered under endoscopic vision. Epimyocardial
      electrodes were implanted through the endoscope onto all four chambers. Standard
      haemodynamic measurements and pacing measurements were carried out. RESULTS: Both
      methods were deployed in the first three individuals. Superior endorsement of
      rigid endoscopy, due to better orientation and stability, led to its exclusive
      deployment in the remaining 14 individuals. Access to the implantation sites was
      quick (<10 min). A plastic cover had to be applied to reduce arrhythmia
      (VentricularExtraSystoles(bare): 17 +/- 2.2 min(-1) vs
      VentricularExtraSystoles(cover): 5 +/- 1.9 min(-1); n = 4). Measured pacing
      parameters were comparable with classic endocardial-derived thresholds. Post
      mortem examination revealed no relevant damage/injury and/or bleeding in the
      heart and circumjacent tissue. There was no evidence of injury at the
      implantation sites and the corresponding pericardium. The electrodes showed
      excellent anchorage inside the myocardial tissue (penetration depths: 3 +/-
      0.2mm) and resisted high tractive forces. CONCLUSION: Flexible endoscopy is not
      suitable for exclusive deployment inside the pericardial space, whereas rigid
      endoscopy presented itself as a safe, fast and simple approach for epimyocardial
      lead implantation using an insulating trocar. Without cover, malignant arrhythmia
      constrains the implementation of video-assisted pericardioscopic surgery (VAPS).
      Subxiphoid VAPS permits optimal lead positioning under direct vision without
      fluoroscopy, without the breach of the pleural space and with a short procedural
      duration (<60 min). Our standardised minimal-invasive approach allows
      visualisation and intervention, potentially of all intrapericardial structures.

PMID- 20675150
TI  - NEXT = new events in xurgical technology.

PMID- 20675152
TI  - Voluntary stepping behavior under single- and dual-task conditions in chronic
      stroke survivors: A comparison between the involved and uninvolved legs.
AB  - OBJECTIVE: If balance is lost, quick step execution can prevent falls. Research
      has shown that speed of voluntary stepping was able to predict future falls in
      old adults. The aim of the study was to investigate voluntary stepping behavior,
      as well as to compare timing and leg push-off force-time relation parameters of
      involved and uninvolved legs in stroke survivors during single- and dual-task
      conditions. We also aimed to compare timing and leg push-off force-time relation
      parameters between stroke survivors and healthy individuals in both task
      conditions. METHODS: Ten stroke survivors performed a voluntary step execution
      test with their involved and uninvolved legs under two conditions: while focusing
      only on the stepping task and while a separate attention-demanding task was
      performed simultaneously. Temporal parameters related to the step time were
      measured including the duration of the step initiation phase, the preparatory
      phase, the swing phase, and the total step time. In addition, force-time
      parameters representing the push-off power during stepping were calculated from
      ground reaction data and compared with 10 healthy controls. RESULTS: The involved
      legs of stroke survivors had a significantly slower stepping time than uninvolved
      legs due to increased swing phase duration during both single- and dual-task
      conditions. For dual compared to single task, the stepping time increased
      significantly due to a significant increase in the duration of step initiation.
      In general, the force time parameters were significantly different in both legs
      of stroke survivors as compared to healthy controls, with no significant effect
      of dual compared with single-task conditions in both groups. CONCLUSIONS: The
      inability of stroke survivors to swing the involved leg quickly may be the most
      significant factor contributing to the large number of falls to the paretic side.
      The results suggest that stroke survivors were unable to rapidly produce muscle
      force in fast actions. This may be the mechanism of delayed execution of a fast
      step when balance is lost, thus increasing the likelihood of falls in stroke
      survivors.

PMID- 20675151
TI  - Time-of-flight secondary ion mass spectrometry imaging demonstrates the specific
      localization of deca-bromo-diphenyl-ether residues in the ovaries and adrenal
      glands of exposed rats.
AB  - Deca-bromo-diphenyl ether (DBDE) is one of the most efficient brominated flame
      retardant (BFR) available on the market. We recently demonstrated that when
      administered to female rat by oral route, DBDE is efficiently absorbed, with the
      highest residual concentrations found in two endocrine glands, namely the adrenal
      glands and the ovaries. Time-of-flight secondary ion mass spectrometry (TOF-SIMS)
      imaging, a technique usually used for the study of endogenous compounds, was
      applied for the first time to a persistent organic pollutant, allowing to detect
      and to precisely localize DBDE residues in these two target tissues. The
      detection of the bromide ion ((81)Br isotope) by TOF-SIMS mass spectrometry
      imaging allowed us to demonstrate a marked cortical tropism of DBDE residues for
      the adrenal glands in female rats dosed per os 2 mg.kg(-1) DBDE, daily, over 96
      h. In ovaries, DBDE residues were found to be concentrated in spots corresponding
      to part of the corpora lutea. Hepatic residues of DBDE were found to be
      homogeneously distributed. Due to the intrinsic toxicity of DBDE, its
      accumulation in the adrenal glands and the ovaries may be connected to the
      mechanisms of actions by which DBDE could trigger endocrine disruption in
      mammals.

PMID- 20675153
TI  - Repair results of 2-tendon rotator cuff tears utilizing the transosseous
      equivalent technique.
AB  - BACKGROUND: The purpose of this study was to examine the healing rate of 2-tendon
      rotator cuff tears repaired by the use of a transosseous-equivalent (TOE) suture
      bridge technique. MATERIALS AND METHODS: Forty-three patients with combined
      supraspinatus and infraspinatus tendon tears underwent arthroscopic repair using
      TOE technique. Forty of these patients were then evaluated by MRI and clinical
      exam at a minimum of 1-year follow-up to determine the rate of healing of the
      repair and clinical outcomes associated with healing. RESULTS: Eighty-three
      percent of the repairs demonstrated intact rotator cuff repairs at a mean of 16
      months post-op. Larger tears (3.5 vs 2.8 cm) were associated with failure (P =
      .01), as was more advanced fatty infiltration (Goutallier 1.3 vs 0.3, P = .01).
      Age was not different between intact and nonintact tendons. Strength was the only
      clinical finding that differed between intact and nonintact tendons. CONCLUSION:
      Two-tendon tears of the rotator cuff can heal at a high rate with the use of TOE
      suture bridge repair technique. Furthermore, tear size and Goutallier grading
      were negatively correlated with postoperative healing. The incremental
      improvement in the rate of observed rotator cuff healing still does not translate
      to statistical differences in the objective shoulder scoring systems.

PMID- 20675154
TI  - The timing of rotator cuff repair for the restoration of function.
AB  - INTRODUCTION: This study was developed to test the hypothesis that there is a
      period in which a painful, traumatic rotator cuff tear, with associated weakness
      and the inability to abduct above shoulder level, should be repaired to allow for
      improvement in function. METHODS: Forty-two consecutive, prospectively followed
      patients met the criteria for entrance into this study. Of those, 36 patients
      were available for a minimum 9 months follow-up (average, 31 months; range, 9-71)
      by office visit. Patient outcomes were measured using the UCLA End-Result and
      ASES scoring systems. Patient variables, including time from injury to repair,
      tear size, degree of preoperative fat infiltration, patient satisfaction, and
      improvement in pain, were evaluated for their association with surgical outcome
      using independent t testing. Time to repair was evaluated at 0-2 months, 2-4
      months, and greater than 4 months. RESULTS: Pain scores improved from 7 to 1.4 (P
      < .01) and active elevation improved from 55 degrees  to 133 degrees  (P < .01).
      UCLA/ASES scores improved from 8/30 to 26/79, respectively (P < .01, P < .01).
      All but 2 of the 36 patients were satisfied with their result. Preoperative fatty
      atrophy did not correlate with postoperative function. Rotator cuff tear size had
      no influence on patient outcome if repaired before 4 months. Massive tears
      repaired after 4 months had the worst outcome. CONCLUSION: Our results emphasize
      that the treatment outcome for traumatic rotator cuff tears of all sizes, with
      associated weakness, is not compromised up to 4 months after their injury.

PMID- 20675155
TI  - Delayed valgus instability and proximal migration of the radius after radial head
      prosthesis failure.

PMID- 20675156
TI  - Correlation of psychomotor findings and the outcome of a physical therapy program
      to treat scapular dyskinesis.
AB  - BACKGROUND: This pilot study was performed to investigate the influence of
      psychomotor skills on the outcome of a specific nonoperative program (scapular
      dyskinesis-program) to treat scapular dyskinesis. MATERIALS AND METHODS: Fifteen
      patients (group A) with positive and 11 patients (group B) with a negative
      outcome after physical therapy were included. To test the psychomotor skills of
      the patients the Motorische Leistungsserie (MLS) was used. The test results of
      the patients of group A were then compared with those of group B. RESULTS: For 2
      parameters, a significant correlation could be detected. However, due to the
      small sample size, a clear but statistically insignificant difference could be
      found for several other factors. CONCLUSION: We, therefore, hypothesize that
      psychomotor skills testing is a potential method to predict the outcome of
      nonoperative treatment for scapular dyskinesis. Further investigations with a
      larger sample size are necessary to confirm this assumption.

PMID- 20675157
TI  - Injection of embryonic median ganglionic eminence cells or fibroblasts within the
      amygdala in rats kindled from the piriform cortex.
AB  - BACKGROUND: Intracerebral infusion of anticonvulsant agent secreting cells has
      proven to raise the threshold for seizure generation in epileptogenic areas.
      Median ganglionic eminence (MGE) is the main embryonic region where future
      GABAergic cells originate. Here we report the results of intraamygdaline grafting
      of MGE cells versus fibroblasts in a piriform cortex kindling model of epilepsy
      in the rat. MATERIAL AND METHODS: Rats were implanted with an electrode in the
      left piriform cortex and subjected to infusion at the left basolateral amygdala
      of cells obtained from the MGE of embryos or fibroblasts. Some of the donor cells
      were obtained from transgenic rats expressing the green fluorescent protein
      (GFP). Seizure and neurologic behavior were recorded, and inmunohistochemical and
      ultrastructural studies were carried out. RESULTS: Cells obtained from the
      embryonic MGE elevated both the afterdischarge and the seizure threshold
      progressively, being significant 3 weeks after their injection. On the contrary,
      fibroblasts injected into the amygdala raised the seizure thresholds the first
      week, the effect weaning during the following weeks. Fibroblasts and MGE cells
      were shown at the injected amygdala. No behavioral side effects were recorded in
      either experimental group. CONCLUSION: MGE cells implanted at the amygdala may
      control the focal component of temporolimbic seizures. This effect may be
      mediated by local release of GABA.

PMID- 20675158
TI  - COX-2 over-expression correlates with VEGF and tumour angiogenesis in canine
      mammary cancer.
AB  - This study was designed to investigate the possible roles of cyclooxygenase-2
      (COX-2) and vascular endothelial growth factor (VEGF) in canine mammary cancer
      angiogenesis. Immunohistochemistry was performed on 70 tumours (28 benign and 42
      malignant) in order to detect COX-2 and VEGF expression. Microvessel density
      (MVD) was determined by CD31 immunolabelling to assess tumour angiogenesis. There
      was a significantly higher expression of COX-2 (P<0.001), VEGF (P<0.001) and MVD
      (P<0.001) in malignant compared to benign tumours. In the malignant group, the
      MVD of COX-2 positive tumours was significantly higher than that of COX-2
      negative tumours (P=0.026). A similar association was observed for VEGF (P<0.001)
      positive tumours. The results from this study suggested that over-expression of
      COX-2 and VEGF may contribute to increased angiogenesis and aggression in
      malignant tumours.

PMID- 20675159
TI  - Urocortin in dogs: a new platform to develop future research in veterinary
      cardiology.

PMID- 20675161
TI  - GPU-accelerated molecular modeling coming of age.
AB  - Graphics processing units (GPUs) have traditionally been used in molecular
      modeling solely for visualization of molecular structures and animation of
      trajectories resulting from molecular dynamics simulations. Modern GPUs have
      evolved into fully programmable, massively parallel co-processors that can now be
      exploited to accelerate many scientific computations, typically providing about
      one order of magnitude speedup over CPU code and in special cases providing
      speedups of two orders of magnitude. This paper surveys the development of
      molecular modeling algorithms that leverage GPU computing, the advances already
      made and remaining issues to be resolved, and the continuing evolution of GPU
      technology that promises to become even more useful to molecular modeling.
      Hardware acceleration with commodity GPUs is expected to benefit the overall
      computational biology community by bringing teraflops performance to desktop
      workstations and in some cases potentially changing what were formerly batch-mode
      computational jobs into interactive tasks.

PMID- 20675160
TI  - Peripheral N-methyl-d-aspartate receptors contribute to mechanical
      hypersensitivity in a rat model of inflammatory temporomandibular joint pain.
AB  - The aim of this study was to determine whether peripheral N-methyl-d-aspartate
      (NMDA) receptors are involved in inflammation-induced mechanical hypersensitivity
      of the temporomandibular joint (TMJ) region. We developed a rat model of
      mechanical sensitivity to Complete Freund's Adjuvant (CFA; 2MUl containing 1MUg
      Mycobacterium tuberculosis)-induced inflammation of the TMJ and examined changes
      in sensitivity following injection of NMDA receptor antagonists (dl-2-amino-5
      phosphonovaleric acid (AP5) or Ifenprodil) with CFA. CFA injected into the TMJ
      resulted in an increase in mechanical sensitivity relative to pre-injection that
      peaked at day 1 and lasted for up to 3days (n=8, P<0.05). There was no change in
      mechanical sensitivity in vehicle-injected rats at any time-point (n=9). At day
      1, there was a significant increase in mechanical sensitivity in animals injected
      with CFA+vehicle (n=7) relative to those injected with vehicle alone (n=7,
      P<0.05), and co-injection of AP5 (n=6) or Ifenprodil (n=7) with CFA blocked this
      hypersensitivity. Subcutaneous injection of AP5 (n=7) and Ifenprodil (n=5)
      instead of into the TMJ had no significant effect on CFA-induced hypersensitivity
      of the TMJ region. Western blot analysis revealed constitutive expression of the
      NR1 and NR2B subunits in trigeminal ganglion lysates. Immunohistochemical studies
      showed that 99% and 28% of trigeminal ganglion neurons that innervated the TMJ
      contained the NR1 and NR2B subunits respectively. Our findings suggest a role for
      peripheral NMDA receptors in inflammation-induced pain of the TMJ region.
      Targeting peripheral NMDA receptors with peripheral application of NMDA receptor
      antagonists could provide therapeutic benefit and avoid side effects associated
      with blockade of NMDA receptors in the central nervous system.

PMID- 20675162
TI  - Detection of His-tagged Long-R3-IGF-I in a black market product.
AB  - OBJECTIVE: Performance-enhancing substances are illicitly used in elite or
      amateur sports and may be obtained from the black market due to a cheaper and
      easier availability. Although various studies have shown that black market
      products frequently do not contain the declared substances, enormous amounts of
      illegally produced and/or imported drugs are confiscated from athletes or at
      customs with alarming results concerning the outcome of the analyses of the
      ingredients. This case report describes the identification of His-tagged Long-R3
      IGF-I, which is usually produced for biochemical studies, in an injection vial.
      DESIGN: The ingredients were isolated by immunoaffinity purification and
      identified by nano-UPLC, high-resolution/high accuracy mass spectrometry of the
      intact and trypsinated substance and by an enzyme-linked immunosorbent assay.
      RESULTS: (Tandem) mass spectra characterized the protein as Long-R3-IGF-I with a
      His6-tag attached to the C-terminus by the linker amino acids Leu-Glu.
      CONCLUSION: His-tags are commonly added to proteins during synthesis to allow a
      convenient and complete purification of the final product and His-tags are
      subsequently removed by specific enzymes when being attached to the N-terminus.
      The effects of His-tagged Long-R3-IGF-I in humans have not been elucidated or
      described and the product may rather be a by-product from biochemical studies
      than synthesized for injection purposes.

PMID- 20675163
TI  - Enzymatic activity of methionine adenosyltransferase variants identified in
      patients with persistent hypermethioninemia.
AB  - Methionine adenosyltransferases (MAT's) are central enzymes in living organisms
      that have been conserved with a high degree of homology among species. In the
      liver, MAT I and III, tetrameric and dimeric isoforms of the same catalytic
      subunit encoded by the gene MAT1A, account for the predominant portion of total
      body synthesis of S-adenosylmethionine (SAM), a versatile sulfonium ion
      containing molecule involved in a variety of vital metabolic reactions and in the
      control of hepatocyte proliferation and differentiation. During the past 15years
      28 MAT1A mutations have been described in patients with elevated plasma
      methionines, total homocysteines at most only moderately elevated, and normal
      levels of tyrosine and other aminoacids. In this study we describe functional
      analyses that determine the MAT and tripolyphosphatase (PPPase) activities of 18
      MAT1A variants, six of them novel, and none of them previously assayed for
      activity. With the exception of G69S and Y92H, all recombinant proteins showed
      impairment (usually severe) of MAT activity. Tripolyphosphate (PPPi) hydrolysis
      was decreased only in some mutant proteins but, when it was decreased MAT
      activity was always also impaired.

PMID- 20675164
TI  - Iron metabolism in macrophages from HFE hemochromatosis patients.
AB  - HFE-linked hereditary hemochromatosis is a common form of iron-overload disease
      in European populations. We studied the role of HFE in macrophage iron
      metabolism. Patients under venesection treatment had higher EPO levels and
      drastically reduced levels of transferrin receptor (TfRC and TfR2) mRNA, and also
      decreased levels of HAMP mRNA in macrophages cultured in autologous serum.
      Macrophages from C282Y/C282Y patients cultured either in autologous serum or in
      FBS with or without iron supplementation, had elevated CYBRD1 (cytochrome b
      reductase 1), SLC40A1 (ferroportin) and FTL (ferritin L) mRNA levels. Those
      incubated with holo-Tf also showed lower levels of TfRC and TfR2 mRNA. Iron flux
      from C282Y/C282Y macrophages incubated with a low concentration of non
      transferrin-bound iron (NTBI) was similar to that from wild-type macrophages, but
      incubation with holo-Tf or high NTBI did not trigger a continuous increase in the
      cytosolic calcein-chelatable iron pool in C282Y/C282Y macrophages conversely to
      wild-type cells. All culture conditions revealed a high level of intracellular
      ferritin in C282Y/C282Y macrophages compared to wild-type cells. These results
      suggest that the non-functional C282Y form of HFE may alter the balance between
      cytosolic calcein-chelatable iron and sequestered iron, thereby disrupting the
      iron uptake and release equilibrium in cells involved in iron storage.

PMID- 20675165
TI  - Amyloid Abeta , cut from APP by beta-secretase BACE1 and gamma-secretase, induces
      apoptosis via opening type-1 porin/VDAC in cell membranes of hypometabolic cells
      A basic model for the induction of apoptosis!?

PMID- 20675166
TI  - A rapid, noninvasive immunoassay for frataxin: utility in assessment of
      Friedreich ataxia.
AB  - Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disorder
      caused by reduced amounts of the mitochondrial protein frataxin. Frataxin levels
      in research studies are typically measured via Western blot analysis from patient
      fibroblasts, lymphocytes, or muscle biopsies; none of these is ideal for rapid
      detection in large scale clinical studies. Recently, a rapid, noninvasive lateral
      flow immunoassay was developed to accurately measure picogram levels of frataxin
      protein and shown to distinguish lymphoblastoid cells from FRDA carriers,
      patients and controls. We expanded the immunoassay to measure frataxin directly
      in buccal cells and whole blood from a large cohort of controls, known carriers
      and patients typical of a clinical trial population. The assay in buccal cells
      shared a similar degree of variability with previous studies conducted in
      lymphoblastoid cells (~10% coefficient of variation in controls). Significant
      differences in frataxin protein quantity were seen between the mean group values
      of controls, carriers, and patient buccal cells (100, 50.2, and 20.9% of control,
      respectively) and in protein extracted from whole blood (100, 75.3, and 32.2%,
      respectively), although there was some overlap between the groups. In addition,
      frataxin levels were inversely related to GAA repeat length and correlated
      directly with age of onset. Subjects with one expanded GAA repeat and an
      identified frataxin point mutation also carried frataxin levels in the disease
      range. Some patients displaying an FRDA phenotype but carrying only a single
      identifiable mutation had frataxin levels in the FRDA patient range. One patient
      from this group has a novel deletion that included exons 2 and 3 of the FXN gene
      based on multiplex ligation-dependent probe amplification (MLPA) analysis of the
      FXN gene. The lateral flow immunoassay may be a useful means to noninvasively
      assess frataxin levels repetitively with minimal discomfort in FRDA patients in
      specific situations such as clinical trials, and as a complementary diagnostic
      tool to aid in identification and characterization of atypical patients.

PMID- 20675167
TI  - ["Good practices" and patient satisfaction].
AB  - OBJECTIVE: The Patient Autonomy Act should contribute to a "patient-centred"
      health care. The study objectives were to determine to what extent patients
      believe that their basic rights under the LAP (best practices) are being met.
      Secondly, to study the relationship between this performance and reported patient
      satisfaction levels. MATERIALS & METHODS: A total of 13,773 patients were
      interviewed (31.7% >60 years and 53.6% women) receiving health care at 21 Spanish
      public hospitals. The number of "good practices" (GP) was analysed using
      descriptive statistics; relationship between GP and satisfaction was measured
      using logistic regression. RESULTS: The medical discharge information was one of
      the most established practices. The compliance level ranged from 97.4% of parents
      of children over 6 years in paediatric service and 76.2% of patients attending
      obstetric services. The welcome process (Odds Ratio 3.53, IC-95% CI; 1.95-6.41,
      P<0.001), informed consent (Odds Ratio 2.77, 95% CI; 1.40-5.47), to recognize
      which type of professional was providing care at all the times (Odds Ratio 3.36,
      95% CI; 1.96-5.78), were the aspects that increased probability that the patient
      felt satisfied. CONCLUSIONS: Compliance to patient rights was increased in all
      services analysed. When these rights are respected patient satisfaction
      increases.

PMID- 20675168
TI  - [Statistical Process Control (SPC) can help prevent treatment errors without
      increasing costs in radiotherapy].
AB  - PURPOSE: Statistical Process Control (SPC) was applied to monitor patient set-up
      in radiotherapy and, when the measured set-up error values indicated a loss of
      process stability, its root cause was identified and eliminated to prevent set-up
      errors. MATERIALS AND METHODS: Set up errors were measured for medial-lateral
      (ml), cranial-caudal (cc) and anterior-posterior (ap) dimensions and then the
      upper control limits were calculated. Once the control limits were known and the
      range variability was acceptable, treatment set-up errors were monitored using
      sub-groups of 3 patients, three times each shift. These values were plotted on a
      control chart in real time. RESULTS: Control limit values showed that the
      existing variation was acceptable. Set-up errors, measured and plotted on a X
      chart, helped monitor the set-up process stability and, if and when the stability
      was lost, treatment was interrupted, the particular cause responsible for the non
      random pattern was identified and corrective action was taken before proceeding
      with the treatment. CONCLUSION: SPC protocol focuses on controlling the
      variability due to assignable cause instead of focusing on patient-to-patient
      variability which normally does not exist. Compared to weekly sampling of set-up
      error in each and every patient, which may only ensure that just those sampled
      sessions were set-up correctly, the SPC method enables set-up error prevention in
      all treatment sessions for all patients and, at the same time, reduces the
      control costs.

PMID- 20675169
TI  - [The induced prescription: a problem that conceals deficiencies in prescription
      management].

PMID- 20675170
TI  - [A program to protocolize nursing care].
AB  - OBJECTIVE: To decrease variability in clinical practice and to standardise and
      develop a systematic care programusing nursing care protocols. MATERIALS AND
      METHODS: The Directorate of Nursing of the Gregorio Maranon Hospital decided to
      develop a systematic program to produce nursing care protocols in 2004. It
      followed 5 phases: preparation, processing, dissemination, evaluation and
      updating. The program was based on the methodology for continuous improvement
      cycle (PDCA). Particular attention was paid to the evaluation phase, and to the
      three types of tools used: evaluation of the process and performance indicators
      and a survey on the perception of professionals. RESULTS: A total of 30 protocols
      and 80 procedures were developed. They were evidence based, accessible, available
      for updating and with evaluation indicators. DISCUSSION: Nursing care protocols
      decrease the variability of clinical practice. They homogenize care and increase
      the involvement of professionals. The evaluation of the process, outcomes and
      adherence of professionals is imperative for continuous improvement.

PMID- 20675171
TI  - [Multidisciplinary coordination to ensure correct patient medication: medication
      reconciliation].

PMID- 20675172
TI  - High HIV knowledge relates to low stigma in pharmacists and university health
      science students in Guyana, South America.
AB  - OBJECTIVES: The objective of this study was to investigate HIV knowledge and its
      relation to HIV stigma among health science students and pharmacists in Guyana,
      South America. This study also evaluated how the Public Health Strengthening in
      Guyana Project's (PHSGP) HIV/AIDS/STI educational initiatives influenced HIV
      knowledge levels among health science students at the University of Guyana.
      METHODS: A total of 119 individuals, consisting of pharmacists (n=42) and health
      science students (n=77) participated in this cross-sectional study. All
      participants completed validated measures of HIV knowledge and HIV stigma.
      RESULTS: Overall, health science students scored high on knowledge about HIV risk
      factors and modes of HIV infection, but were less knowledgeable about more
      complex HIV treatment issues such as adherence and drug resistance. Students who
      had received educational HIV training had significantly higher levels of HIV
      knowledge than those who had not received training. Pharmacists had excellent
      knowledge regarding HIV risk factors and modes of infection, but had some
      important gaps in knowledge regarding the importance of HIV medication adherence
      and drug resistance. Overall, low levels of HIV stigma were endorsed, and those
      with higher HIV knowledge reported lower HIV stigma. CONCLUSIONS: Although the
      HIV curriculum has enhanced HIV knowledge, gaps in HIV knowledge remain, such as
      complex HIV treatment issues. The results of this study are discussed within the
      context of the challenges of HIV capacity building in resource-poor countries.

PMID- 20675173
TI  - Physical exercise for the prevention and treatment of type 2 diabetes.
AB  - The prevalence of type 2 diabetes is rapidly increasing worldwide, yet its
      primary prevention and treatment are still a challenge. The objectives of this
      review are to assess the effects of exercise on the prevention of type 2 diabetes
      in high-risk individuals and on glycaemic control in type 2 diabetic patients.
      Considering the available reports, there is unequivocal and strong evidence that
      physical exercise can prevent or delay progression to type 2 diabetes in subjects
      with impaired glucose tolerance. Also, lifestyle interventions, including diet
      and physical exercise, can result in a reduction of around 50% in diabetes
      incidence that persists even after the individual lifestyle counselling has
      stopped. In addition, short-term randomized studies have confirmed that physical
      training based on endurance and/or resistance exercises can also improve blood
      glucose control in type 2 diabetics with a mean glycated haemoglobin decrease of
      0.6%. Thus, physical exercise should be part of any therapeutic strategy to slow
      the development of type 2 diabetes in high-risk individuals and to improve
      glucose control in type 2 diabetes.

PMID- 20675174
TI  - Ultrasound for wool dyeing and finishing.
AB  - The effects of ultrasound at 35-39 kHz on several wool dyeing and finishing
      processes have been investigated as a way of reducing environmental impact.
      Ultrasound improved the effectiveness of cleaning scoured wool in water and to a
      lesser extent in water-nonionic surfactant. Scanning electron microscopy did not
      indicate any surface damage. Fluorescence microscopy revealed increased levels of
      sulphydryl groups on the wool surface suggesting ultrasound caused the removal of
      thioester-bound lipids. Ultrasound pre-treatment increased the effectiveness of
      subsequent oxidative-reductive bleaching, but had no effect on the uptake of acid
      levelling and acid milling dyes. The pre-treatment retarded the uptake of
      reactive dye, possibly by increasing the crystallinity of the fibre or removing
      surface bound lipids. Ultrasound did not improve dyeing under conditions that are
      currently used in industry, but did show potential to reduce the chemical and
      energy requirements of dyeing wool with reactive and acid milling dyes, but not
      acid levelling dyes.

PMID- 20675175
TI  - Coating a stainless steel plate with silver nanoparticles by the sonochemical
      method.
AB  - Ultrasound irradiation is used for the deposition of silver nanoparticles with an
      average size of 40 nm on the surface of a stainless steel plate. The sonochemical
      reduction of an AgNO(3) solution (water, ethylene glycol and aqueous ammonia) was
      carried out at 30 degrees C. Irradiation was done with a high intensity
      ultrasonic horn (Ti horn from Sonics and Materials VCX600, 20 kHz, 600 W at 70%
      efficiency) under an argon flow. The influence of the distance of the stainless
      steel plate from the sonicator tip varied, and a homogeneous coating without
      agglomeration was achieved at a distance of 1 cm. By controlling the reaction
      conditions and the distance from the tip we could achieve a homogeneous monolayer
      coating of silver nanoparticles on the stainless steel surface. The silver
      deposited stainless steel plates were analysed by UV-visible, XRD, SEM and FIB
      analyses.

PMID- 20675176
TI  - Mechanical design of an intracranial stent for treating cerebral aneurysms.
AB  - Endovascular treatment of cerebral aneurysms using stents has advanced markedly
      in recent years. Mechanically, a cerebrovascular stent must be very flexible
      longitudinally and have low radial stiffness. However, no study has examined the
      stress distribution and deformation of cerebrovascular stents using the finite
      element method (FEM) and experiments. Stents can have open- and closed-cell
      structures, and open-cell stents are used clinically in the cerebrovasculature
      because of their high flexibility. However, the open-cell structure confers a
      risk of in-stent stenosis due to protrusion of stent struts into the normal
      parent artery. Therefore, a flexible stent with a closed-cell structure is
      required. To design a clinically useful, highly flexible, closed-cell stent, one
      must examine the mechanical properties of the closed-cell structure. In this
      study, we investigated the relationship between mesh patterns and the mechanical
      properties of closed-cell stents. Several mesh patterns were designed and their
      characteristics were studied using numerical simulation. The results showed that
      the bending stiffness of a closed-cell stent depends on the geometric
      configuration of the stent cell. It decreases when the stent cell is stretched in
      the circumferential direction. Mechanical flexibility equal to an open-cell
      structure was obtained in a closed-cell structure by varying the geometric
      configuration of the stent cell.

PMID- 20675177
TI  - Influence of disturbances on the control of PC-mouse, goal-directed arm
      movements.
AB  - This study concerns the influence of visuomotor rotating disturbance on motion
      dynamics and brain activity. It involves using a PC-mouse and introducing a
      predefined bias angle between the direction of motion of the mouse pointer and
      that of the screen cursor. Subjects were asked to execute three different tasks,
      designed to study the effect of visuomotor rotation on direction control, extent
      control or the two together. During each task, mouse movement, screen cursor
      movement and electroencephalograph (EEG) signals were recorded. An algorithm was
      used to detect and discard EEG signals contaminated by artifacts. Movement
      performance indexes and brain activity are used to evaluate motion control,
      tracking ability, learning and control. The results suggest the direction control
      is planned before the movement and controlled by an adaptive control while extent
      control is controlled by a real-time feedback. The measurements also confirm that
      increased motion and/or brain activity occur for bias angles in the ranges +/-(90
      120 degrees ) for both direction and extension controls. After-effects when
      changing the angle of visual rotation have been seen to be proportional to the
      variation in the adaptation angle.

PMID- 20675178
TI  - Estimation of distributed arterial mechanical properties using a wave propagation
      model in a reverse way.
AB  - To estimate arterial stiffness, different methods based either on distensibility,
      pulse wave velocity or a pressure-velocity loop, have been proposed. These
      methods can be employed to determine the arterial mechanical properties either
      locally or globally, e.g. averaged over an entire arterial segment. The aim of
      this study was to investigate the feasibility of a new method that estimates
      distributed arterial mechanical properties non-invasively. This new method is
      based on a wave propagation model and several independent ultrasound and pressure
      measurements. Model parameters (including arterial mechanical properties) are
      obtained from a reverse method in which differences between modeling results and
      measurements are minimized using a fitting procedure based on local sensitivity
      indices. This study evaluates the differences between in vivo measured and
      simulated blood pressure and volume flow waveforms at the brachial, radial and
      ulnar arteries of 6 volunteers. The estimated arterial Young's modulus range from
      1.0 to 6.0MPa with an average of (3.8+/-1.7)MPa at the brachial artery and from
      1.2 to 7.8MPa with an average of (4.8+/-2.2)MPa at the radial artery. A good
      match between measured and simulated waveforms and the realistic stiffness
      parameters indicate a good in vivo suitability.

PMID- 20675179
TI  - Displacement and tuberculosis: recognition in nursing care.
AB  - Through a qualitative of study of public health nurses and their clients in
      Toronto, Canada, displacement is described as a central feature in illness and
      care. Specifically, how client experiences are anchored in circumstances of
      international migration and contagiousness is described, along with how nurses
      take up understandings of displacement as part of their daily work through
      diminishing the social displacement of immigration, connecting here and there,
      and minimizing the displacement of contagiousness. The research illustrates how
      responding to the implacing and displacing elements of the illness experience and
      broader lifecourse can be an important part of professional practice. Moreover it
      highlights how place sensitive geographical inquiry is insightful with respect to
      understanding the interplay between illness, wellbeing, and health care work.

PMID- 20675180
TI  - A framework for identifying similarities among countries to improve cross
      national comparisons of health systems.
AB  - Cross-national research on health system performance can yield important findings
      for public policy purposes. We seek to further this research by examining the
      problem of selection bias, an important methodological issue that investigators
      initially should consider. Because of the logistical difficulties and enormous
      expense involved in collecting voluminous data from many countries, researchers
      often must rely on information contained in data sets of international
      organizations, such as the World Health Organization (WHO) and the Organization
      for Economic Cooperation and Development. Under the circumstances, the
      comparisons that researchers can make will depend to a great extent on the
      availability and richness of data for certain measures. This situation raises the
      potential for selection or experimenter bias. We use multivariate statistics to
      group countries with similar characteristics, an approach that we believe will
      mitigate the problem. We perform a cluster analysis of 186 countries using
      principal components derived from 7 demographic variables and 27 mortality and
      burden of disease variables. Our analysis produced six clusters that we believe
      represent suitable groupings for comparative purposes.

PMID- 20675181
TI  - Learning deformation and structure simultaneously: in situ endograft deformation
      analysis.
AB  - The learning of the shape and appearance behavior of complex anatomical
      structures is of growing importance in the successful use of medical imaging
      data. We propose a method to simultaneously learn a model of shape variation and
      the behavioral structure of objects in volumetric data sets. The algorithm
      performs a group-wise registration of a set of examples, and accounts for the
      heterogeneous deformation or variability properties of the data. We use the
      method for the in situ analysis of endograft deformation in the thoracic aorta
      during the cardiac cycle. The method is based on an emerging model of the shape
      variation, which is learned autonomously from a gated computed tomography
      sequence. It automatically adapts to the highly non-uniform elasticity properties
      of the structure during learning. The resulting deformation model is used for the
      measurement of global and local characteristics of the endograft movement. The
      method allows for the in situ localization of the stent during the cardiac cycle,
      and the measurement of its deformation. Furthermore, it makes the comparison of
      different endograft designs possible, and can serve as a basis for fitting a
      physical model of the endograft- and vessel surface to individual patients. The
      latter is essential for long-term risk assessment of the impact of endografts in
      highly mobile areas. We evaluate the approach on 10 data sets from patients that
      underwent endograft placement after traumatic ruptures of the thoracic aorta.

PMID- 20675183
TI  - Language evolution in the laboratory.
AB  - The historical origins of natural language cannot be observed directly. We can,
      however, study systems that support language and we can also develop models that
      explore the plausibility of different hypotheses about how language emerged. More
      recently, evolutionary linguists have begun to conduct language evolution
      experiments in the laboratory, where the emergence of new languages used by human
      participants can be observed directly. This enables researchers to study both the
      cognitive capacities necessary for language and the ways in which languages
      themselves emerge. One theme that runs through this work is how individual-level
      behaviours result in population-level linguistic phenomena. A central challenge
      for the future will be to explore how different forms of information transmission
      affect this process.

PMID- 20675182
TI  - The multifaceted interplay between attention and multisensory integration.
AB  - Multisensory integration has often been characterized as an automatic process.
      Recent findings indicate that multisensory integration can occur across various
      stages of stimulus processing that are linked to, and can be modulated by,
      attention. Stimulus-driven, bottom-up mechanisms induced by crossmodal
      interactions can automatically capture attention towards multisensory events,
      particularly when competition to focus elsewhere is relatively low. Conversely,
      top-down attention can facilitate the integration of multisensory inputs and lead
      to a spread of attention across sensory modalities. These findings point to a
      more intimate and multifaceted interplay between attention and multisensory
      integration than was previously thought. We review developments in the current
      understanding of the interactions between attention and multisensory processing,
      and propose a framework that unifies previous, apparently discordant, findings.

PMID- 20675184
TI  - Translating DNA damage into cancer cell death-A roadmap for E2F1 apoptotic
      signalling and opportunities for new drug combinations to overcome
      chemoresistance.
AB  - The cellular transcription factor E2F1 has been identified as a tumor suppressor
      regulating the activities of p53 and its homologue TAp73, and promoting apoptosis
      by the activation of a plethora of death pathways. More than 15 years of
      experimentation recognized E2F1 as the key player in apoptosis induced by DNA
      damage in all types of human cancer. This occurs by several mechanisms that
      affect RB-E2F1 interaction, E2F1 stability and its binding to promoters of E2F1
      regulated genes. Recent progress has been made in revealing new proapoptotic
      genes regulated by E2F1 and it seems that many still remain to be discovered.
      However, whereas in the past one focused mainly on identifying E2F1 target genes
      translating cellular stress signals into cell death, today the DNA damage-induced
      regulatory network governing E2F1's ability to induce apoptosis is rapidly
      gaining attention as well. Notably, the lately uncovered role of pRB and E2F3 in
      triggering E2F1-dependent apoptosis through chemotherapy gains our understanding
      of the DNA damage response in normal and tumor cells. In this context a large
      body of evidence indicates that nuclear cofactors targeting E2F1 seem to have a
      major impact on its tumor suppressor function. These new findings are discussed
      in the context of preclinical studies applying E2F1 overexpression in combination
      with genotoxic anticancer agents - called chemogene therapy, thereby providing
      new mechanistic links between the E2F1-induced apoptotic programming and advanced
      cancer phenotype.

PMID- 20675185
TI  - Impact Factor steadily rising and now 3.123!

PMID- 20675186
TI  - Molecular analysis of human group A rotavirus G10P[14] genotype in Slovenia.
AB  - BACKGROUND: Rotavirus G10 genotype is one of the main rotaviruses circulating in
      cattle throughout the world but is also found in asymptomatic and symptomatic
      infections in children, and thought to be acquired through zoonotic transmission.
      OBJECTIVES: To determine the genetic diversity of G10P[14] rotavirus strains
      detected in various regions in Slovenia during a study on the molecular
      epidemiology of rotaviruses conducted in 2007. STUDY DESIGN: Five G10P[14]
      rotavirus strains detected in Slovenia in 2007 were subjected to sequencing and
      phylogenetic analysis of the genes encoding VP7, NSP4 and partial VP4 (VP8*) and
      VP6 rotavirus proteins. RESULTS: Sequence and phylogenetic analysis of the four
      genes analyzed revealed a significant genetic diversity. Overall, the Slovenian
      G10P[14] are divided into two phylogenetic lineages. CONCLUSIONS: These results
      suggest that the G10P[14] strains found in Slovenian children did not emerge from
      a common source but possibly result of at least two independent zoonotic
      transmissions. Phylogenetic analysis and comparison with sequence data available
      in GenBank points towards a bovine origin to these strains.

PMID- 20675188
TI  - EEG latency analysis for hemispheric lateralisation in Landau-Kleffner syndrome.
AB  - OBJECTIVE: To determine the reliability of latency analysis in lateralising the
      origin of epileptiform discharges in pre-surgical assessment of Landau-Kleffner
      syndrome (LKS). METHODS: A computer aided-method was developed to identify
      leading regions and measure inter-hemispheric latencies before and after
      averaging discharges. Scalp and intracranial EEG recordings were studied from
      seven patients undergoing surgical treatment. The laterality suggested by latency
      analysis was compared with that suggested by pharmacological tests. RESULTS:
      Latency analysis of bilateral discharges showed a consistent leading hemisphere.
      The earliest low-amplitude deflections were located in temporal regions in all
      patients. Contralateral low-amplitude deflections, and ipsilateral and
      contralateral earliest large negative peaks were recorded in temporal and less
      frequently in parasagittal regions. Presurgical inter-hemispheric latencies
      ranged between 8 and 48 ms for the deflections and between 4 and 30 ms for the
      peaks. The leading hemisphere identified by latency analysis of the earliest low
      amplitude deflections coincided with that suggested by pharmacological tests in
      all 7 patients, whereas latency of later components coincided in 6. CONCLUSIONS:
      Latency analysis appears to be a reliable method to estimate the hemisphere
      driving bilateral discharges in LKS. SIGNIFICANCE: It can be carried out non
      invasively and could be used to confirm, and eventually replace, results from
      pharmacological tests.

PMID- 20675187
TI  - Prediction of human voluntary movement before it occurs.
AB  - OBJECTIVE: Human voluntary movement is associated with two changes in
      electroencephalography (EEG) that can be observed as early as 1.5 s prior to
      movement: slow DC potentials and frequency power shifts in the alpha and beta
      bands. Our goal was to determine whether and when we can reliably predict human
      natural movement BEFORE it occurs from EEG signals ONLINE IN REAL-TIME. METHODS:
      We developed a computational algorithm to support online prediction. Seven
      healthy volunteers participated in this study and performed wrist extensions at
      their own pace. RESULTS: The average online prediction time was 0.62+/-0.25 s
      before actual movement monitored by EMG signals. There were also predictions that
      occurred without subsequent actual movements, where subjects often reported that
      they were thinking about making a movement. CONCLUSION: Human voluntary movement
      can be predicted before movement occurs. SIGNIFICANCE: The successful prediction
      of human movement intention will provide further insight into how the brain
      prepares for movement, as well as the potential for direct cortical control of a
      device which may be faster than normal physical control.

PMID- 20675189
TI  - Cervical cancer: does our message promote screening? A pilot study in a South
      African context.
AB  - PURPOSE: The purpose of the study was to explore if cervical cancer information
      presented in a non-stigmatizing manner could promote screening in women living in
      a resource poor environment in Tshwane, South Africa. METHODS: An exploratory,
      contextual, quantitative door-to-door survey was conducted. The sampling method
      was convenience (n = 105). Structured interviews were used to gather self
      reported data. Chi-square tests were used for secondary data analyses. RESULTS:
      The study provided evidence that presenting information on cervical cancer in a
      non-stigmatizing manner based on the theme of self protection promoted cervical
      screening. The study further provided evidence that women preferred a cervical
      cancer message that does not focus on the sexual risk factors of this disease.
      More than a third of the sample preferring a message introducing cervical cancer
      as a sexually transmitted infection (n = 32) were of the opinion that this
      message were stigmatizing, blameful and displayed misunderstanding of their
      lives. CONCLUSIONS: Cervical cancer screening is indeed not simple. The screening
      rate not only in South Africa but many other countries serves as proof. It can
      therefore not be afforded to add to the barriers by presenting information on
      cervical cancer in a way perceived as stigmatizing and blameful. Presenting
      information in way that women prefer might not only promote cervical screening,
      but might motivate them in such a way that they are screened.

PMID- 20675190
TI  - Symptom prevalence and changes of symptoms over ten days in hospitalized patients
      with advanced cancer: a descriptive study.
AB  - PURPOSE: This prospective study described symptom prevalence and changes of
      symptoms over ten days in patients with advanced cancer admitted to two Swiss
      tertiary care hospitals because of symptoms, deterioration of health status, or
      complications. METHOD: Prevalence, frequency, severity of and distress from 31
      symptoms were assessed repeatedly with the Memorial Symptom Assessment Scale in
      103 patients at admission, and on day six (n = 76) and ten (n = 53) of the
      hospital stay. Repeated measures regression models were used for analysis.
      RESULTS: The mean number of symptoms experienced was 13.0 (SD = 6.1) at
      admission, 9.7 (SD = 5.4) on day six, 9.3 (SD = 4.9) on day ten. Lack of energy
      was most prevalent (82% of patients) and most frequent, pain was most severe and
      distressing; symptom scores of all but 4 symptoms (weight loss, "I don't look
      like myself," vomiting, itching) were >2 on a scale from 0 to 4. Over time, the
      average number of symptoms decreased significantly for the whole group (P <
      .0001) and for patients discharged after day six (P = .006), but not for patients
      dropping out after day six due to worsening health status (P = .78). Individual
      trajectories showed that symptom prevalence varied greatly within and among
      patients. CONCLUSIONS: High symptom prevalence at admission, identification of
      areas in symptom management with the potential for improvement, and wide
      variability in symptom prevalence among patients call for comprehensive symptom
      assessment and individual treatment, especially in patients with a worsening
      health status.

PMID- 20675191
TI  - Direct and indirect roles of the LTbetaR pathway in central tolerance induction.
AB  - Medullary thymic epithelial cells (mTECs) play a critical role in thymic negative
      selection of autoreactive thymocytes, especially for thymocytes specific for
      peripheral tissue-restricted self-antigens (TRA). Deficiency in lymphotoxin b
      receptor (LTbetaR) is associated with peripheral tissue inflammation, but whether
      this is caused by defective negative selection has been unclear; the significance
      of the LTbetaR pathway for negative selection is evident in some models but not
      others. Here, we revisit the data and clarify the role of LTbetaR in mTEC
      development and function and thymic TRA expression. These processes are discussed
      as potential mechanisms for LTbetaR-mediated control of negative selection.

PMID- 20675192
TI  - Collaborative study of irregular erythrocyte antibodies in Japan: results from
      the Japanese study group of allo-immunity and antigen diversity in Asian
      populations.
AB  - As a national study, we evaluated the frequencies of irregular erythrocyte
      antibodies (Abs) by gender and history of transfusion or pregnancy. In total,
      data from 248,785 patients were analyzed, from whom 4222 irregular erythrocyte
      Abs were detected in 3554 cases (1.43%). Abs frequencies in these 4222 cases were
      as follows: anti-E, 26%; anti-Le(a), 26%; anti-P(1), 11%; anti-M, 6%; anti-E+c,
      4%; anti-Fy(b), 4%; anti-Di(a), 3%; anti-Le(b), 3%; and anti-D, 2%. In pregnancy,
      anti-D (5%), anti-Jr(a) (3%) and anti-E+c (6%) Abs were, with statistical
      significance, more frequent. Among transfused patients, anti-E (38%), anti-E+c
      (8%), anti-Jk(a) (4%), anti-e+C (2%) and anti-E+Jk(a) (1%) Abs were, with
      statistical significance, more frequent.

PMID- 20675193
TI  - Caution with the published database reviews analyzing the off-label use of
      recombinant activated factor VII (rFVIIa) in cardiac surgery.

PMID- 20675194
TI  - Quantitative MAIPA: Comparison of different MAIPA protocols.
AB  - INTRODUCTION: In a screening setting, maternal anti-HPA 1a antibody level has
      been found to be a good prognostic tool to identify newborns at risk for severe
      NAIT. AIM: Identify the optimal MAIPA protocol for quantitation of anti-HPA 1a
      antibodies. MATERIALS AND METHODS: Plasma were analysed for anti-HPA 1a
      antibodies using different monoclonal antibodies, lyophilized or fresh platelets
      and MAIPA protocols. RESULTS: The anti-HPA 1a antibody level varied significantly
      when different monoclonal antibodies were used. However, there was a strong
      correlation between maternal anti-HPA 1a antibody level and platelet count in the
      newborn. The sensitivity of the assay depended on the adopted MAIPA protocol.
      CONCLUSION: Consistent tests results are of importance for the clinical impact of
      the test.

PMID- 20675195
TI  - The effects of hypertension on the paediatric brain: a justifiable concern.
AB  - The prevalence of hypertension in children is increasing but its neurological
      effects are under-recognised. Here, we describe acute and chronic effects of
      childhood hypertension on the nervous system. Acute neurological involvement
      ranges from posterior reversible encephalopathy syndrome to, possibly, infarction
      and haemorrhage. Children with chronic hypertension are likely to have learning
      disabilities and deficiencies in executive function, which are potentially
      reversible with antihypertensive treatment. These cognitive defects may be
      secondary to abnormal regulation of cerebral blood flow. Raised blood pressure in
      childhood could also contribute to the early development of atherosclerosis,
      which can have both short-term and long-term adverse effects on vasculature.
      Clinical studies are needed to better define the full clinical range of
      paediatric hypertension on a child's nervous system. Furthermore, accurate
      biomarkers to define cognitive abnormalities and cerebral involvement need to be
      identified.

PMID- 20675196
TI  - High intestinal and systemic levels of decoy receptor 3 (DcR3) and its ligand
      TL1A in active ulcerative colitis.
AB  - Decoy receptor-3 (DcR3) is a member of the TNF receptor superfamily of proteins,
      which has been implicated in anti-apoptotic and anti-inflammatory pathways, via
      binding to TL1A, LIGHT and Fas-L. The role of the TL1A/DcR3 ligand/receptor pair
      in ulcerative colitis (UC) has not been studied. We investigated the systemic
      (peripheral blood) and local (large intestine) expression of DcR3 and TL1A in 64
      patients with UC and 56 healthy controls. DcR3 serum concentrations were highly
      elevated in patients with active UC (P<0.0001 vs. healthy controls). This
      elevation was clearly related to the presence of intestinal inflammation as it
      was less frequently observed in patients in remission (P=0.003 vs. active UC)
      whereas effective treatment resulted in disappearance or significant decrease of
      serum DcR3 (P=0.006 vs. pre-treatment). Furthermore, DcR3 mRNA transcripts were
      significantly elevated in inflamed areas of the colon (P=0.002 vs. non-affected
      of the same patient). In addition to DcR3 elevation, we found increased
      circulating levels of TL1A in patients with either active or inactive UC in
      comparison to healthy controls (P<0.001 for both). We conclude that elevated
      serum DcR3 may serve as an indicator of active colonic inflammation in patients
      with UC. TL1A/DcR3-mediated pathways may participate in the pathogenesis of UC.

PMID- 20675197
TI  - Impact of trough IgG on pneumonia incidence in primary immunodeficiency: A meta
      analysis of clinical studies.
AB  - Primary immunodeficiency disease (PIDD) associated with hypogammaglobulinemia is
      typically treated with immunoglobulin replacement therapy. When administered as
      intravenous immunoglobulin (IVIG), an IgG trough occurs prior to the next
      replacement dose. While frequently measured, IgG trough levels required to
      minimize infection risk are not established. To address this question, all
      available studies evaluating trough IgG and pneumonia incidence in PIDD patients
      with hypogammaglobulinemia receiving IVIG were quantitatively combined by meta
      analysis. Seventeen studies with 676 total patients and 2,127 patient-years of
      follow-up were included. Pneumonia incidence declined by 27% with each 100mg/dL
      increment in trough IgG (incidence rate ratio, 0.726; 95% confidence interval,
      0.658-0.801). Pneumonia incidence with maintenance of 500 mg/dL IgG trough levels
      (0.113 cases per patient-year) was 5-fold that with 1000 mg/dL (0.023 cases per
      patient-year). This meta-analysis provides evidence that pneumonia risk can be
      progressively reduced by higher trough IgG levels up to at least 1000 mg/dL.

PMID- 20675198
TI  - Latency to first psychogenic nonepileptic seizure upon admission to inpatient EEG
      monitoring: evidence for semiological differences.
AB  - Two hundred sixteen consecutive patients diagnosed with psychogenic nonepileptic
      seizures (PNES) admitted to the epilepsy monitoring unit at our institution over
      a 4.5-year period were retrospectively identified. PNES were classified into four
      semiological subcategories: major motor (n=123), minor motor (n=38), akinetic
      (n=32), and subjective/experiential (n=23). The median latency to first PNES for
      the entire population was 7 hours (range: <1 to 207 hours), confirming previous
      observations that the latency to first PNES on admission is often <24 hours. The
      novel observation is that latency to first PNES was dependent on type. The median
      latency to first PNES was significantly prolonged in both the minor motor
      (median=21 hours) and subjective/experiential (median=22 hours) groups as
      compared with the major motor (median=5 hours) and akinetic (median=4 hours)
      groups. Thus, patients with one of these two subtypes may require longer
      admissions to capture the event of interest and confirm the diagnosis.

PMID- 20675199
TI  - The effect of vagus nerve stimulation therapy on body mass index in children.
AB  - The effects of vagus nerve stimulation on weight in individuals with epilepsy are
      not fully characterized. A retrospective review was performed of all pediatric
      patients who underwent placement of a vagus nerve stimulator at Duke University
      Medical Center. Baseline body mass index (BMI) percentile was compared with
      percentile on follow-up visits. We studied 23 patients who had undergone VNS
      placement during the period 2001-2009. Baseline BMI percentile was 61.7 +/- 34.3.
      We had a power of 81% to detect a difference of 20 in BMI percentile from
      baseline to last follow-up. At the 1-year follow-up (mean=345 +/- 112 days) and
      last follow-up (mean 4.2 +/- 2.4 years) the average BMI percentile was 61.6 +/-
      31.88 and 56.09 +/- 30.83, respectively. There was no significant difference in
      BMI percentile as compared with baseline at the 1-year and last follow-up visits
      (P=0.992 and 0.681, respectively). Long-term pediatric VNS therapy did not have a
      major clinically significant effect on BMI percentile during an average follow-up
      of more than 4 years.

PMID- 20675200
TI  - Progesterone prevents allodynia after experimental spinal cord injury.
AB  - Chronic pain after spinal cord injury represents a therapeutic challenge.
      Progesterone, a neuroprotective steroid, has been shown to modulate nociceptive
      thresholds, whereas its effect on neuropathic pain needs to be further explored.
      In this study, we evaluated whether progesterone could ameliorate pain-associated
      behaviors in animals subjected to a spinal cord hemisection. The development of
      mechanical and cold allodynia was assessed in injured male rats treated with
      daily injections of progesterone or vehicle. The expression of N-methyl-D
      aspartate receptor (NMDAR) subunits, protein kinase C gamma (PKCgamma),
      preprodynorphin (ppD), and kappa opioid receptor (KOR), key players in chronic
      pain mechanisms, was determined in the dorsal spinal cord. Twenty-eight days
      after injury, all vehicle-treated animals presented allodynic behaviors and a
      marked increase in NMDAR subunits, PKCgamma, and ppD mRNA levels, with no changes
      in KOR mRNA levels. Progesterone prevented the development of mechanical
      allodynia and reduced the painful responses to cold stimulation. In correlation
      with the attenuation of pain behaviors, the steroid prevented NMDAR subunits and
      PKCgamma mRNAs upregulation, did not modify the elevated ppD mRNA levels, but
      increased KOR expression. In conclusion, progesterone modulates neuropathic pain
      after spinal cord injury, creating a favorable molecular environment that may
      decrease spinal nociceptive signaling. PERSPECTIVE: The present study suggests
      that progesterone administration could represent an interesting strategy to
      modulate neuropathic pain circuits after spinal cord injury. Further studies are
      needed to investigate the potential progesterone receptors involved in these
      actions.

PMID- 20675201
TI  - Competitive interactions between vestibular and cardiac rhythms in the modulation
      of muscle sympathetic nerve activity.
AB  - We tested the hypothesis that vestibular and cardiac rhythms compete to modulate
      muscle sympathetic nerve activity (MSNA) in human subjects. Sinusoidal galvanic
      vestibular stimulation was applied across the mastoid processes at each subject's
      cardiac frequency and at +/-0.1, +/-0.2, +/-0.3 and +/-0.6 Hz. Cyclic modulation
      of MSNA was weakest at this central frequency (44.8+/-2.3%; n=8); significantly
      lower than when delivered 0.1 Hz lower (57.7+/-3.3%) or 0.1 Hz higher (56.3+/
      3.3%) than this frequency. We conclude that vestibular inputs compete with
      baroreceptor inputs operating at the cardiac rhythm, with vestibular modulation
      of MSNA being lowest when competition with the baroreceptors is highest.

PMID- 20675202
TI  - [Insulin resistance as a mechanism of adaptation during human evolution].
AB  - The recent application of concepts of evolution to human disease is proving
      useful to understand certain pathophysiological mechanisms of different entities
      that span genomic alterations of immunity, respiratory and hormone function, and
      the circulatory and neural systems. However, effort has concentrated on
      explaining the keys to adaptation that define human metabolism and, since the
      early 1960s, several theories have been developed. This article reviews some of
      the hypotheses postulated in recent years on the potential benefit of insulin
      resistance and discusses the most recent knowledge. The concept of the thrifty
      gene seems to have been definitively refuted by current knowledge. The current
      paradigm describes an interaction between the metabolic and the immune systems
      resulting from their coevolution, promoted by evolutionary pressures triggered by
      fasting, infection and intake of different foods. The activation and regulation
      of these ancient mechanisms in integrated and interdependent areas defines
      insulin resistance as a survival strategy that is critical during fasting and in
      the fight against infection. The relationship with some components of the diet
      and, particularly, with the symbiotic intestinal microflora points to new
      paradigms in understanding the pathophysiology of obesity, metabolic syndrome and
      type 2 diabetes mellitus.

PMID- 20675203
TI  - [Evaluation of metabolic control targets in patients with type 2 diabetes
      mellitus].
AB  - OBJECTIVE: To evaluate the extent to which metabolic targets in type 2 diabetes
      (DM-2) are achieved in the Endocrinology and Clinical Nutrition Unit of the
      Hospital Puerta del Mar in Cadiz (Spain) from 2005 to 2008. METHOD: The database
      included in the computer application HP-Doctor used for all patients attended in
      our unit (admissions, consultations and peripheral centers) was analyzed. All
      patients with a principal or secondary diagnosis of DM-2 were included. Clinical
      characteristics, chronic complications, drug treatment and the percentage of
      patients who achieved annual mean targets of glycosylated hemoglobin (HbA1c) and
      low-density lipoprotein cholesterol (LDLc) were analyzed. RESULTS: From 2005 to
      2008, the number of DM-2 patients with computerized records increased by 108.7%.
      In 2008, 1,177 patients were evaluated. A total of 10.8% were active smokers, 53%
      had hypertension, and 51.2% and 12.6% presented with retinopathy and
      cardiovascular disease, respectively. During the study period, the percentage of
      patients with a mean HbA1c <7% was similar (2005: 31.7% 2008: 30.4%), those with
      LDLc <100 mg/dl increased from 19.2% to 25.6% and only 9.2% of patients achieved
      both targets, HbA1c <7% and LDLc <100 mg/dl. CONCLUSIONS: In 2008, only 30% of DM
      2 patients achieved a mean HbA1c < 7% and only 25% had LDLc < 100 mg/dl.
      Metabolic control in DM-2 patients should be improved.

PMID- 20675204
TI  - [Acute toxic hepatitis induced by methimazole: two cases].

PMID- 20675205
TI  - [Bilateral primary renal Burkitt lymphoma presenting with acute renal failure].
AB  - We report the case of a 12 year-old girl who presented with acute renal failure
      with massive infiltration in both kidneys due to a Burkitt lymphoma that was
      diagnosed by percutaneous renal biopsy. This case fulfilled all the diagnostic
      criteria of Malbrain et al. to be considered as primary renal non-Hodgkin
      lymphoma. We discuss the differential diagnosis with other processes that present
      with acute renal failure and bilateral nephromegaly, and the mechanism by which
      renal failure occurs. It should be emphasised that this patient showed clinical
      symptoms compatible with rheumatic disease at diagnosis. The possibility of joint
      and muscle problems should be considered as a sign of onset of hematopoietic
      disease.

PMID- 20675206
TI  - Selective intrauterine growth restriction in monochorionic twins:
      pathophysiology, diagnostic approach and management dilemmas.
AB  - Selective intrauterine growth restriction (sIUGR) in monochorionic twins is
      associated with a substantial increase in perinatal mortality and morbidity for
      both twins. Clinical evolution depends on the combination of the effects of
      placental insufficiency in the IUGR twin with inter-twin blood transfer through
      placental anastomoses. Classification of sIUGR into types according to the
      characteristics of umbilical artery diastolic flow in the IUGR twin permits the
      differentiation of clinical and prognostic groups. sIUGR type I has normal
      diastolic flow and relatively good outcome. Type II is defined by persistently
      absent/reverse end-diastolic flow and is associated with a high risk of
      intrauterine demise of the IUGR twin and/or very preterm delivery. Type III is
      defined by the presence of intermittent absent/reverse end-diastolic flow
      (iAREDF), and is associated with 10-20% risk of unexpected fetal demise of the
      smaller twin and 10-20% risk of neurological injury in the larger twin. The
      management strategy for sIUGR with abnormal umbilical artery Doppler (types II
      and III) remains a challenge, and may include elective fetal therapy or close
      surveillance with fetal therapy or elective delivery in the presence of severe
      fetal deterioration. Small clinical series reporting the use of cord occlusion or
      laser therapy in severe cases suggest that the outcome of the larger twin might
      be improved. There is probably no single optimal strategy, since decisions will
      ultimately be influenced by the severity of IUGR, gestational age, parents'
      wishes and technical issues.

PMID- 20675207
TI  - Latex deposition on suture needles and contamination of surgical wounds.

PMID- 20675208
TI  - Comparison of different stepwise screening strategies for type 2 diabetes:
      Finding from Danish general practice, Addition-DK.
AB  - AIM: To examine attendance, number of people with T2DM and costs of three
      different stepwise screening strategies for T2DM in general practice (GP).
      METHODS: Diabetes risk questionnaires were mailed to individuals aged 40-69 years
      from 45 general practices in 2001-2002 and individuals at high risk for T2DM,
      were asked to contact their GP to arrange a screening test. In 2005-2006, 26
      general practices were randomised into two different opportunistic screening
      programmes (OP-direct and OP-subsequent) and risk questionnaires were distributed
      to individuals aged 40-69 years during GP consultations. In the OP-direct
      approach, high-risk individuals were offered to start the screening during the
      actual consultation while high-risk individuals in the OP-subsequent approach,
      were invited to a screening test at a later date. We report attendance, number of
      people with T2DM and costs of each screening approach. RESULTS: The mail
      distributed approach identified 0.8% of the target population with T2DM, the OP
      direct approach and the OP-subsequent approach, 0.9% and 0.5% respectively. Cost
      per person with T2DM was in the mail-distributed approach: ? 1058, OP-direct
      approach: ? 707 and the OP-subsequent approach: ? 727. CONCLUSION: This study
      indicates that opportunistic screening identifies the same level of unknown
      diabetes as a mail-distributed approach but with lower costs.

PMID- 20675209
TI  - Australian Aboriginal kinship: a means to enhance maternal well-being.
AB  - BACKGROUND: The relocation of women from their rural communities to birth in a
      centralised hospital is becoming increasingly common as maternity units close in
      rural areas of Australia. The significance for Aboriginal women when they are
      denied the support of kin around the time of birth but have that support re
      established postnatally is explored. METHODS: This paper gathered data from
      multiple sources including in-depth interviews with three Aboriginal mothers and
      one partner; observational field notes; and during debriefing, the knowledge and
      experience of an Aboriginal midwife. Thematic analysis was utilised to both
      explore and critique the collected data. FINDINGS AND DISCUSSION: Aboriginal
      women are particularly disadvantaged by maternity unit closures in rural areas of
      the south eastern Australian state of New South Wales (NSW). However, contrary to
      the expectation that this would result in postnatal mental health problems, the
      support the Aboriginal participants in this study received from kin may have had
      a mediating effect which enhanced their well-being and possibly prevented mental
      ill health. RECOMMENDATIONS: Recommendations relate to strategies and policies
      that have the potential to increase community governance and feelings of cultural
      safety for Aboriginal childbearing women living in rural areas. CONCLUSION: While
      the practice of forcing Aboriginal women to relocate around the time of birth has
      a negative impact on perinatal health outcomes, kinship support may be a
      mediating factor.

PMID- 20675210
TI  - Inhibition of ERK1/2 prevents neural and mesendodermal differentiation and
      promotes human embryonic stem cell self-renewal.
AB  - Extracellular signal-regulated kinases (ERKs) have many important functions
      during embryogenesis. However, their role in embryonic stem (ES) cells is
      controversial. Previous studies reported that, in contrast to mouse ES cells,
      human ES cells differentiate if ERK1/2 is inhibited. We reexamined the role of
      ERK1/2 in human ES cells using a chemically defined culture system and found that
      when ERK1/2 is blocked with specific chemical inhibitors, neural and
      mesendodermal differentiation is prevented, but cells become sensitive to BMP
      induced differentiation. Inhibition of ERK1/2 significantly reduced the
      clonogenicity of human ES cells by preventing cell adhesion and survival. When
      this negative effect was avoided, we were able to maintain human ES cell self
      renewal for more than 3months in the presence of ERK1/2 inhibitors in a
      chemically defined culture system containing FGF2 and activin A but no BMP4. Our
      results suggest that the functional outcome of FGF/ERK1/2 signaling in human ES
      cells is influenced by the relative levels of activin A/TGFbeta and BMP activity.
      Moreover, activation of ERK1/2 in human ES cells is required for proper neural
      and mesendodermal differentiation. In contrast to mouse ES cells, a low level of
      BMP4 is sufficient to initiate extraembryonic differentiation when ERK1/2 is
      inhibited.

PMID- 20675211
TI  - The medical home, preventive care screenings, and counseling for children:
      evidence from the Medical Expenditure Panel Survey.
AB  - OBJECTIVE: Little is known about the role of the medical home in promoting
      essential preventive health care services in the general pediatric population.
      This study examined associations between having a medical home and receipt of
      health screenings and anticipatory guidance. METHODS: We conducted a cross
      sectional analysis of the 2004-2006 Medical Expenditure Panel Survey (MEPS). Our
      sample included 21 055 children aged 0 to 17 years who visited a health care
      provider in the year prior to the survey. A binary indicator of the medical home
      was developed from 22 questions in MEPS, reflecting 4 of the 7 American Academy
      of Pediatrics' recommended components of the medical home: accessible, family
      centered, comprehensive, and compassionate care. Multivariable logistic
      regression was used to examine the association between the medical home and
      receipt of specific health screenings and anticipatory guidance, controlling for
      confounding variables. RESULTS: Approximately 49% of our study sample has a
      medical home. The medical home, defined when the usual source of care is a person
      or facility, is significantly associated with 3 health screenings (ie, weight,
      height, and blood pressure) and several anticipatory guidance topics (ie, advice
      about dental checkups, diet, exercise, car and bike safety), with odds ratios
      ranging from 1.26 to 1.54. CONCLUSIONS: The medical home is associated with
      increased odds of children receiving some health screenings and anticipatory
      guidance. The medical home may provide an opportunity to improve the delivery of
      these services for children.

PMID- 20675236
TI  - Patent ductus arteriosus: when does it become a significant lesion for full-term
      newborns?

PMID- 20675237
TI  - Understanding neonatal jaundice: a perspective on causation.
AB  - Neonatal jaundice can be best understood as a balance between the production and
      elimination of bilirubin, with a multitude of factors and conditions affecting
      each of these processes. When an imbalance results because of an increase in
      circulating bilirubin (or the bilirubin load) to significantly high levels
      (severe hyperbilirubinemia), it may cause permanent neurologic sequelae
      (kernicterus). In most infants, an increase in bilirubin production (e.g., due to
      hemolysis) is the primary cause of severe hyperbilirubinemia, and thus reducing
      bilirubin production is a rational approach for its management. The situation can
      become critical in infants with an associated impaired bilirubin elimination
      mechanism as a result of a genetic deficiency and/or polymorphism. Combining
      information about bilirubin production and genetic information about bilirubin
      elimination with the tracking of bilirubin levels means that a relative
      assessment of jaundice risk might be feasible. Information on the level of
      bilirubin production and its rate of elimination may help to guide the clinical
      management of neonatal jaundice.

PMID- 20675238
TI  - Risk factors for liver steatosis in obese children and adolescents.
AB  - BACKGROUND: Concurrent with the recent rise of the incidence in obesity,
      nonalcoholic fatty liver disease is increasingly prevalent in childhood. The aim
      of this study was to identify non-invasive biomarkers for liver steatosis in
      obese children and adolescents. METHODS: We used a cross-sectional study to
      examine risk factors for liver steatosis in obese children and adolescents. Sixty
      nine obese subjects aged 6-17 years were recruited. The diagnosis of liver
      steatosis was made by liver ultrasonography. Anthropometric, serum biochemical
      variables, and oral glucose tolerance tests were measured. RESULTS: Thirty-eight
      (55.1%) subjects had liver steatosis. Elevated alanine aminotransferase levels (>
      30 IU/L in boys and >19 IU/L in girls) were found in 27 (71.1%) of the 38
      subjects with liver steatosis. In multivariate logistic regression analysis,
      liver steatosis was associated with waist circumference and the change of plasma
      glucose level before and after oral glucose tolerance testing (C-OGTT). For every
      5 cm increase in waist circumference, there was an odds ratio of 1.391 for
      predicting liver steatosis (95% confidence interval: 1.009-1.916, p = 0.044). C
      OGTT was the only laboratory variable that independently predicted liver
      steatosis, with an odds ratio of 1.198 (95% confidence interval: 1.022-1.404, p =
      0.026) for each 5 mg/dL of increase. CONCLUSION: In this hospital-based sample of
      obese children and adolescents, liver steatosis was common. Liver steatosis was
      positively associated waist circumference and C-OGTT. These findings have
      implications for screening liver steatosis in obese children and adolescents.

PMID- 20675239
TI  - Comparison of clinical characteristics and neutrophil values in omental
      infarction and acute appendicitis in children.
AB  - BACKGROUND: Omental infarction is a rare occurrence in children. It is often
      diagnosed during surgery for suspected appendicitis. This study investigated the
      use of clinical and laboratory data for distinguishing between omental infarction
      and acute appendicitis. METHODS: Seven patients with surgically and
      pathologically proven omental infarction and 28 age- and sex-matched patients
      with acute appendicitis were included in this study. The clinical
      characteristics, imaging study results and laboratory data were analyzed.
      RESULTS: All 35 patients had right lower quadrant abdominal pain at presentation.
      The frequency of nausea and fever were significantly lower in the omental
      infarction group compared with the acute appendicitis group (p< 0.001 and p=
      0.018, respectively). In laboratory studies, the white blood cell count, C
      reactive protein value and neutrophil percentage were all higher in the acute
      appendicitis group compared with the omental infarction group (p= 0.001, p<
      0.001, and p= 0.008, respectively). It was possible to separate patients with
      omental infarction from those with acute appendicitis based on a neutrophil
      percentage of less than 77% (sensitivity 100%, specificity 100%). CONCLUSIONS:
      Results of the current study suggest that omental infarction should be considered
      as a possible diagnosis in patients presenting with right lower quadrant
      abdominal pain without nausea or fever, and with a neutrophil percentage below
      77%.

PMID- 20675240
TI  - Management of patent ductus arteriosus in term or near-term neonates with
      respiratory distress.
AB  - BACKGROUND: Respiratory distress and patent ductus arteriosus (PDA) in neonates
      are mutually perpetuating. Contrary to the situation in premature infants, the
      recognition, clinical relevance and optimal management of PDA in full-term
      neonates are unclear. The present study aimed to identify PDA as a possible cause
      of respiratory distress in term and near-term neonates, and to examine the
      clinical responsiveness of PDA to different treatment modalities in mature
      gestational-age neonates. METHODS: Patients with gestational ages of over 34
      weeks were included in this retrospective chart review; they had PDA as the sole
      recognizable cause of respiratory distress and were free of all other diseases.
      Clinical responsiveness to different regimens, including conservative treatment,
      drug therapy with preload reduction and inotropic agent with or without the
      addition of indomethacin, and surgical intervention were analyzed. RESULTS: Forty
      four neonates qualified for this study. Six received no treatment and their
      cardiorespiratory symptoms resolved within 1 week (regimen A). Symptoms in 11
      neonates were relieved after use of diuretic and inotropic agents (regimen B).
      Twelve neonates became asymptomatic without further intervention after
      indomethacin treatment in addition to preload reduction and inotropes (regimen
      C). A total of 15 of the 44 infants underwent PDA ligation (regimen D) due to
      persistent heart failure following regimens B or C, but had speedy resolution of
      respiratory symptoms following surgery. There were significant differences in
      birth body weight and hemodynamic variation based on left atrium to aortic root
      dimensional ratio between the treatment (regimens B, C and D) and non-treatment
      (regimen A) groups (p < 0.05). CONCLUSION: PDA plays an important role in
      prolonging respiratory distress in term or near-term neonates. Although most
      infants respond to noninvasive medical treatment, surgical ligation during the
      neonatal period is warranted in certain mature infants. Surgical treatment should
      be considered in patients with smaller birth body weights and those with
      increased left atrium to aortic root dimensional ratios.

PMID- 20675241
TI  - Evaluation of right ventricle function in children with primary nephrotic
      syndrome.
AB  - BACKGROUND: We aimed to evaluate right ventricle (RV) function in children with
      primary nephrotic syndrome (PNS). METHODS: RV hemodynamics were evaluated by
      Doppler echocardiography in 50 children with PNS (aged 2.5-12 years), either at
      PNS onset (n = 37) or relapse (n = 13), and in 50 normal controls. Heart rate,
      stroke volume, cardiac output, RV enddiastolic and end-systolic volume, RV
      ejection fraction, RV end-diastolic pressure, RV peak systolic and end-systolic
      pressure were determined from pressure-volume loops. The maximal rates of RV
      pressure upstroke and fall (dP/d t(max) and dP/d t(min), respectively) were
      calculated. Effective pulmonary arterial elastance was calculated as end-systolic
      pressure divided by stroke volume. Plasma tumor necrosis factor-alpha (TNF-alpha)
      and insulin-like growth factor 1 (IGF-1) were also measured. RESULTS: RV end
      diastolic pressure was increased by an average of 20% in 39 of the patients with
      PNS, whereas RV ejection fraction was reduced by an average of 15% compared with
      controls (p < 0.05 for both). Cardiac output and stroke volume were maintained,
      indicating compensation at the expense of increased RV end-diastolic and end
      systolic volumes and increased RV filling pressure (p < 0.05). Plasma TNF-alpha
      was elevated in patients with PNS (326 +/- 117 kU/L vs. 75 +/- 23 kU/L, p <
      0.05); IGF-1 was similar in PNS patients and controls. CONCLUSION: Right
      ventricle function was impaired in children with PNS. The characteristics were
      unrelated to blood pressure and IGF-1, but may be correlated with TNF-alpha and
      disease duration. Further studies are needed to evaluate the etiology and
      clinical implications of this abnormality.

PMID- 20675242
TI  - Management of congenital cystic adenomatoid malformation and bronchopulmonary
      sequestration in newborns.
AB  - BACKGROUND: Congenital cystic adenomatoid malformation (CCAM) and
      bronchopulmonary sequestration (BPS) are major embryonic pulmonary developmental
      anomalies. Early surgical excision is becoming an increasingly common option. We
      investigated the clinical features and management of patients with CCAM and BPS
      at the National Taiwan University Hospital. METHODS: We conducted a retrospective
      review of neonates diagnosed with CCAM and/or BPS at the Hospital from July 1995
      to January 2008. Prenatal examination, postnatal presentation, management and
      patient outcome were analyzed. We also propose a concise algorithm for the
      practical management of these conditions. RESULTS: Sixteen patients were
      recruited including eight (50%) with CCAM, five (31%) with BPS and three (19%)
      with mixed-type lesions (CCAM with BPS). Thirteen (81%) patients were diagnosed
      antenatally at a median gestational age of 20 weeks. Eleven (69%) patients
      underwent surgical resection before 6 months of age because of respiratory
      distress or repeated pulmonary infection. There were no surgery-related
      complications among the seven patients who underwent early surgery within 1 month
      of age. Five (31%) patients remained asymptomatic and did not undergo surgery.
      All patients survived with no limitations to daily activity during follow-up
      periods of 1-8 years. CONCLUSION: The high proportion of mixed-type lesions
      suggests that CCAM and BPS may share the same developmental ancestry. Early
      surgical resection within 1 month of age is safe in symptomatic patients.

PMID- 20675243
TI  - Effect of body weight on temperature control and energy expenditure in preterm
      infants.
AB  - BACKGROUND: The purpose of this study was to compare resting energy expenditure
      (REE) in premature infants of different body weights during weaning from the
      incubator. We hypothesized that premature infants would respond to weaning from
      an incubator with an increase in REE, and that the increment would be larger in
      infants with lower body weights than in those with higher body weights. METHODS:
      Stable preterm infants with body weights between 1800-2200 g were enrolled. REE
      was measured using indirect calorimetry at 1 hour before weaning and 3 hours
      after turning off the incubator. REE measurements from infants with higher body
      weight (2000-2200 g, Group A) were compared to those of infants with lower body
      weight (1800-2000 g, Group B). RESULTS: A total of 22 patients were studied (10
      in Group A and 12 in Group B). REE increased significantly after weaning in both
      groups (Group A: from 62 +/- 7 kcal/kg/day to 69 +/- 8 kcal/kg/day, p = 0.045 and
      Group B: from 65 +/- 5 kcal/kg/day to 70 +/- 7 kcal/kg/day, p = 0.001). However,
      there was no significant difference in REE increments between the two groups.
      CONCLUSION: REE increased significantly in infants during weaning from an
      incubator. The increase in REE increment was similar in smaller (1800-2000 g) and
      larger (2000-2200 g) babies in this study. Weaning of preterm babies from an
      incubator may be safely started when their body weight reaches 1800 g.

PMID- 20675244
TI  - Neonatal tetanus after home delivery: report of one case.
AB  - Neonatal tetanus is a rare disease in developed countries, but remains common in
      developing countries. Pregnant women immigrating to Taiwan from developing
      countries may carry a risk of neonatal tetanus to the child, because of
      inadequate tetanus toxoid immunization and inappropriate postnatal cord care.
      Many young pediatricians in Taiwan are unfamiliar with this disease. Herein, we
      describe the clinical course of a newborn with neonatal tetanus, who was admitted
      with complaints of difficult feeding and muscle rigidity. After mechanical
      ventilation for 58 days and a prolonged hospital stay, the infant was discharged
      in good condition. It is important to maintain a high index of suspicion for
      neonatal sepsis when infants present with seizure-like symptoms, in order to
      allow its early diagnosis and appropriate treatment.

PMID- 20675245
TI  - Congenital colonic atresia: report of one case.
AB  - Colonic atresia is a very rare cause of intestinal obstruction, and surgical
      management is the mainstay of therapy. A case of congenital colonic atresia is
      reported in a full-term neonate who presented with delayed passage of meconium,
      abdominal distention and bilious vomiting. The present case and the pertinent
      literature are discussed, with an emphasis on surgical management.

PMID- 20675246
TI  - Bloody nipple discharge in an adolescent girl: unusual presentation of juvenile
      fibroadenoma.
AB  - Fibroadenoma accounts for 50-60% of all breast mass lesions in adolescents. It
      usually presents as a unilateral palpable breast mass. In contrast, bloody nipple
      discharge rarely occurs in childhood. We report the case of a 12-year-old
      pubertal girl who presented with a solitary breast mass and bloody nipple
      discharge. Physical examination and ultrasound showed a right breast subareolar
      homogenous mass, about 2.5 cm in diameter, near the lactiferous duct. Histologic
      diagnosis of the mass revealed a juvenile fibroadenoma with infarction and
      hemorrhage. The unusual clinical presentation and possible etiology in this
      patient is described, and the proper management of bloody nipple discharge in
      pediatric patients is discussed in association with a literature review.

PMID- 20675248
TI  - CT appearances following laparoscopic partial nephrectomy for renal cell
      carcinoma using a rolled cellulose bolster.
AB  - PURPOSE: To describe the evolving computed tomography (CT) appearances of a
      cellulose surgical bolster used as a hemostatic agent in patients who undergo
      laparoscopic partial nephrectomy for renal cell carcinoma. MATERIALS AND METHODS:
      We retrospectively reviewed the follow-up CT studies of 33 patients with stage
      T1N0M0 renal carcinoma who underwent laparoscopic partial nephrectomy using a
      rolled, oxidized, regenerated cellulose sheet sutured in place as a bolster in
      the parenchymal defect. Thirteen patients undergoing laparoscopic partial
      nephrectomy without the use of a bolster were also evaluated to differentiate
      imaging features. RESULTS: The bolster-related masses were significantly larger
      than those seen in the non-bolster patients. There was a decrease in size of the
      post-operative bolster-related mass with time. The bolster shape evolved with
      time, initially appearing oval, and becoming irregular with decreasing size.
      Equivocal increase in attenuation of 10-20 HU was seen in 6 patients. Increase in
      attenuation of greater than 20 HU was seen in 3 patients. There was no evidence
      of tumor recurrence in any of the patients. Invagination of fat was seen in two
      bolster-related masses at 18 months or greater. CONCLUSIONS: Cellulose bolster
      has a variable appearance on follow-up CT exams. Evolutionary features include
      reduction in bolster size and shape with time leading finally to non
      visualization. Bolster enhancement can mimic abscesses and tumor recurrence.

PMID- 20675249
TI  - Multiple FDG-avid sclerosing hemangiomas mimicking pulmonary metastases in a case
      of soft tissue sarcoma.
AB  - Non-neoplastic lesions have been known to mimic malignancies and metastases on
      positron emission tomography/computed tomography. We report the rare occurrence
      of multiple fluorodeoxyglucose-concentrating sclerosing hemangiomas in a patient
      with soft tissue sarcoma mimicking lung metastases.

PMID- 20675250
TI  - Pulling back the curtain: improving reviews in environmental health.

PMID- 20675252
TI  - From devastation comes hope.

PMID- 20675253
TI  - An uneven path forward: the history of methylmercury toxicity research.

PMID- 20675255
TI  - Bringing the bugs back in: environmental health research model combines
      toxicology and infectious disease.

PMID- 20675257
TI  - Emergency responder health: what have we learned from past disasters?

PMID- 20675258
TI  - The gene behind arsenic hyperaccumulation.

PMID- 20675259
TI  - Cancer report examines environmental hazards.

PMID- 20675260
TI  - Between the devil and the deep blue sea: dispersants in the gulf of Mexico.

PMID- 20675261
TI  - Soy formula of "minimal concern".

PMID- 20675262
TI  - Body of proof: biomonitoring data reveal widespread bisphenol A exposures.

PMID- 20675263
TI  - Breaking patterns of disease: early-life clues may predict long-term health.

PMID- 20675264
TI  - Evolution in environmental health: incorporating the infectious disease paradigm.

PMID- 20675265
TI  - In utero exposure to bisphenol A shifts the window of susceptibility for mammary
      carcinogenesis in the rat.
AB  - BACKGROUND: Bisphenol A (BPA) is a ubiquitous environmental chemical with
      reported endocrine-disrupting properties. OBJECTIVE: Our goal in this study was
      to determine whether prenatal exposure to BPA predisposes the adult rat mammary
      gland to carcinogenesis. METHODS: Pregnant rats were treated orally with 0, 25,
      or 250 microg BPA/kg body weight (BW) from gestation day (GD) 10 to GD21. For
      tumorigenesis experiments, prenatally exposed female offspring received a single
      gavage of 7,12-dimethylbenz(a)anthracene (DMBA; 30 mg/kg BW) on postnatal day
      (PND) 50, or PND100. RESULTS: Prenatal exposure of the dam to 250 microg BPA/kg
      BW combined with a single exposure of female offspring to DMBA on PND100, but not
      on PND50, significantly increased tumor incidence while decreasing tumor latency
      compared with the control group. Prenatal exposure of the dam to 250 microg
      BPA/kg BW, in the absence of DMBA to the female offspring, increased cell
      proliferation and elicited differential effects at the protein level at PND100
      compared with PND50. Differentially regulated proteins in the mammary gland
      included estrogen receptor-alpha, progesterone receptor-A, Bcl-2, steroid
      receptor coactivators, epidermal growth factor receptor, phospho-insulinlike
      growth factor 1 receptor, and phospho-Raf. CONCLUSIONS: Our study demonstrates
      that oral prenatal exposure to BPA increases mammary cancer susceptibility in
      offspring and shifts the window of susceptibility for DMBA-induced tumorigenesis
      in the rat mammary gland from PND50 to PND100. These changes are accompanied by
      differential effects of prenatal BPA exposure on the expression of key proteins
      involved in cell proliferation.

PMID- 20675266
TI  - Association between lead and cadmium and reproductive hormones in peripubertal
      U.S. girls.
AB  - BACKGROUND: Lead (Pb) and cadmium (Cd) are known reproductive toxicants thought
      to disrupt hormone production throughout sensitive developmental windows,
      although this has not been previously examined in nationally representative
      peripubertal children. OBJECTIVES: We examined the association between blood Pb
      and urinary Cd concentrations and the reproductive hormones inhibin B and
      luteinizing hormone (LH) in girls 6-11 years of age who participated in the cross
      sectional Third National Health and Nutrition Examination Survey (NHANES III)
      (1988-1994). METHODS: Pb (micrograms per deciliter) was measured in whole blood,
      and Cd was measured in urine (nanograms per milliliter). Inhibin B (picograms per
      milliliter) and LH (milli-International units per milliliter) were measured in
      residual sera for 705 girls. Survey logistic regression was used to estimate
      associations with pubertal onset based on inhibin B concentration > 35 pg/mL or
      LH concentration > 0.4 mIU/mL, and multinomial logistic regression was used to
      estimate the association between Pb and increasing categories of hormone
      concentrations. RESULTS: High Pb (>= 5 ug/dL) was inversely associated with
      inhibin B > 35 pg/mL [odds ratio (OR) = 0.26; 95% confidence interval (CI), 0.11
      0.60; compared with Pb < 1 ug/dL]. At 10 and 11 years of age, girls with low Pb
      (< 1 ug/dL) had significantly higher inhibin B than did girls with moderate (1
      4.99 ug/dL) or high Pb (>= 5 ug/dL). In the subsample of 260 girls with levels of
      inhibin B above the level of detection and using survey regression modeling,
      inhibin B levels were lower among girls with both high Pb and high Cd (beta= 
      0.52; 95% CI, -0.09 to -1.04) than among girls with high Pb alone (beta= -0.35;
      95% CI, -0.13 to -0.57), relative to girls with low Pb and low Cd. CONCLUSIONS:
      Higher Pb was inversely associated with inhibin B, a marker of follicular
      development, and estimated effects suggestive of pubertal delays appeared to be
      stronger in the context of higher Cd concentrations. These data underscore the
      importance of Pb and Cd as reproductive toxicants for young girls.

PMID- 20675269
TI  - [Oncologic radiotherapy].

PMID- 20675268
TI  - Artificial lighting as a vector attractant and cause of disease diffusion.
AB  - BACKGROUND: Traditionally, epidemiologists have considered electrification to be
      a positive factor. In fact, electrification and plumbing are typical initiatives
      that represent the integration of an isolated population into modern society,
      ensuring the control of pathogens and promoting public health. Nonetheless,
      electrification is always accompanied by night lighting that attracts insect
      vectors and changes people's behavior. Although this may lead to new modes of
      infection and increased transmission of insect-borne diseases, epidemiologists
      rarely consider the role of night lighting in their surveys. OBJECTIVE: We
      reviewed the epidemiological evidence concerning the role of lighting in the
      spread of vector-borne diseases to encourage other researchers to consider it in
      future studies. DISCUSSION: We present three infectious vector-borne diseases
      Chagas, leishmaniasis, and malaria-and discuss evidence that suggests that the
      use of artificial lighting results in behavioral changes among human populations
      and changes in the prevalence of vector species and in the modes of transmission.
      CONCLUSION: Despite a surprising lack of studies, existing evidence supports our
      hypothesis that artificial lighting leads to a higher risk of infection from
      vector-borne diseases. We believe that this is related not only to the simple
      attraction of traditional vectors to light sources but also to changes in the
      behavior of both humans and insects that result in new modes of disease
      transmission. Considering the ongoing expansion of night lighting in developing
      countries, additional research on this subject is urgently needed.

PMID- 20675267
TI  - Polymorphisms in GSTT1, GSTZ1, and CYP2E1, disinfection by-products, and risk of
      bladder cancer in Spain.
AB  - BACKGROUND: Bladder cancer has been linked with long-term exposure to
      disinfection by-products (DBPs) in drinking water. OBJECTIVES: In this study we
      investigated the combined influence of DBP exposure and polymorphisms in
      glutathione S-transferase (GSTT1, GSTZ1) and cytochrome P450 (CYP2E1) genes in
      the metabolic pathways of selected by-products on bladder cancer in a hospital
      based case-control study in Spain. METHODS: Average exposures to trihalomethanes
      (THMs; a surrogate for DBPs) from 15 years of age were estimated for each subject
      based on residential history and information on municipal water sources among 680
      cases and 714 controls. We estimated effects of THMs and GSTT1, GSTZ1, and CYP2E1
      polymorphisms on bladder cancer using adjusted logistic regression models with
      and without interaction terms. RESULTS: THM exposure was positively associated
      with bladder cancer: adjusted odds ratios (ORs) and 95% confidence intervals
      (CIs) were 1.2 (0.8-1.8), 1.8 (1.1-2.9), and 1.8 (0.9-3.5) for THM quartiles 2,
      3, and 4, respectively, relative to quartile 1. Associations between THMs and
      bladder cancer were stronger among subjects who were GSTT1 +/+ or +/- versus
      GSTT1 null (P(interaction) = 0.021), GSTZ1 rs1046428 CT/TT versus CC
      (P(interaction) = 0.018), or CYP2E1 rs2031920 CC versus CT/TT (P(interaction) =
      0.035). Among the 195 cases and 192 controls with high-risk forms of GSTT1 and
      GSTZ1, the ORs for quartiles 2, 3, and 4 of THMs were 1.5 (0.7-3.5), 3.4 (1.4
      8.2), and 5.9 (1.8-19.0), respectively. CONCLUSIONS: Polymorphisms in key
      metabolizing enzymes modified DBP-associated bladder cancer risk. The consistency
      of these findings with experimental observations of GSTT1, GSTZ1, and CYP2E1
      activity strengthens the hypothesis that DBPs cause bladder cancer and suggests
      possible mechanisms as well as the classes of compounds likely to be implicated.

PMID- 20675270
TI  - Synantocytes: the fifth type of glia? In comparison with astrocytes.
AB  - To date four types of glial cells have been identified in central nervous system:
      astrocytes, oligodendrocytes, microglia, ependymocytes. The latest results
      indicate the existence of the fifth glial type-synantocytes from the Greek word
      synanto that is for contact. Synantocyte processes reach neurons, astrocytes,
      oligodendrocytes, microglia, synapses, myelin sheaths and nervous fibres' nodes
      of Ranvier. Morphologically, synantocytes are similar to astrocytes, but they do
      not contain, like astrocytes, glial fibrillary acidic protein and S-100 beta
      protein. Synantocytes show expression of NG2 surface chondroition sulphate
      proteoglycan. Moreover, these cells in contrast to astrocytes do not have
      membrane transporters for glutamate (Glu), but have receptors for Glu and gamma
      aminobutyric acid, whose activation can contribute to keeping up ion balance in
      CNS. Synantocytes are components of synapses, participate in neuronal
      cytoskeleton stabilization and control myelin integrity, mediate oligodendrocytes
      answer to nervous fibres' damage and form glial scars. Thus, there are evidences
      that synantocytes and astrocytes make separate glial population, playing
      important functions in neuroprotection.

PMID- 20675271
TI  - Identification of chosen apoptotic (TIAR and TIA-1) markers expression in thyroid
      tissues from adolescents with immune and non-immune thyroid diseases.
AB  - The aim of this study was to estimate sodium iodide symporter (NIS) and thyroid
      peroxidase (TPO) expression in thyrocytes from patients with GD and no-toxic
      multinodular goitre (NTMG) in relationship with apoptotic (TIAR and TIA-1)
      markers. The investigation was performed on thyroid cells isolated from
      postoperation thyroid tissues from 15 patients aged 12-21 years old with GD and
      15 cases aged 13-21 years old with NTMG. Detection of NIS and TPO was performed
      by immunohistochemistry. Analysis of apoptotic markers in thyroid tissues was
      performed using antibodies to TIAR and TIA-1 by Western Blot and
      immunohistochemistry. Identification of proapoptotic TIAR and TIA-1 molecules in
      the thyroid tissues revealed a higher expression of both proteins in patients
      with Graves' disease (+++; +, respectively) in comparison to patients with NTNG
      (+; 0). In addition, TIAR expression was detected in three bands [p50, p42, p38
      (kDa)] and TIA-1 in two bands [p22, p17 (kDa)]. using Western Blot test in
      patients with thyroid autoimmune diseases. In patients with NTNG expression of
      both apoptotic proteins was lower and identified in single bands: 42 (kDa) for
      TIAR and 17 (kDa) for TIA-1. The analysis of expression of NIS and TPO in thyroid
      follicular cells was higher in patients with Graves' disease in compared to their
      detection in patients with NTMG. In addition, degree of thyroid antigen
      expression positive correlated with amount of proapoptotic markers (TIAR,
      p<0.001; TIA-1, p<0.025 for NIS; TIAR, p<0.012 for TPO). We conclude that
      elevated expression of NIS and TPO in Graves' disease is associated with higher
      stimulation and activation of apoptosis in thyroid follicular cells during
      autoimmune process.

PMID- 20675272
TI  - Age of menarche in girls with cystic fibrosis.
AB  - Malnutrition, delayed growth and puberty are commonly observed in children
      suffering from cystic fibrosis. The aim of this study was to assess the age of
      menarche in girls with CF using status quo analysis. The relationship between
      types of CFTR mutations and onset of the first menstruation was also evaluated.
      Material was based on somatic data gathered from medical history records of 47
      girls with cystic fibrosis, aged 11-18 years. All girls were patients of the
      Mother and Child Institute in Warsaw (Poland). RESULTS: The age of menarche in
      the girls in the study group was 14.65+/-1.21 years. In comparison with the
      healthy child population, girls with cystic fibrosis experienced menarche with 2
      years' delay. Menstruating girls were found to be statistically older and taller
      than their non-menstruating consorts. Regarding body mass and BMI, a marked
      tendency towards higher parameter values was noted in the menstruating group,
      although the differences did not reach statistical significance. A significant
      relationship between onset of menarche and type of CFTR mutation was found. Girls
      with cystic fibrosis enter puberty later than their peers, in spite of intensive
      medical care. The issue of growth and puberty in children with CF requires
      further detailed investigation under clinical and auxological aspects.

PMID- 20675273
TI  - Inducible nitric oxide synthase in duodenum of children with Giardia lamblia
      infection.
AB  - The investigation were performed on children with Giardia lamblia infection,
      diagnosed on the basis of positive stool tests for Giardia antigen (Elisa) or by
      microscopical detection of trophozoites in duodenal fluid. In duodenal biopsies
      morphological studies and immunohistochemical reaction for inducible nitric oxide
      synthase (iNOS) were performed. The control group was made up of duodenal tissue
      of children with excluded giardiasis and inflammation of the upper part of
      gastrointestinal tract. The duodenal biopsies from children without Giardia
      lamblia infection were found to have a high immunoreactivity for iNOS in
      enterocytes, the cells of intestinal crypts, endothelial cells of vessels and
      connective tissue cells of lamina propria. In children with giardiasis: in some
      biopsies the expression of iNOS was as high as in control group, in others was
      weaker detectable and the shortening of intestinal villi was seen. There were
      also duodenal biopsies with the lack of immunoreactivity for iNOS, with shorter
      villi and a large amount of mucus in the intestinal epithelium. Beside of goblet
      cells, also enterocytes were loaded with mucus. The pathological changes may
      cause malabsorption and also may have a negative influence on the defense of the
      intestinal wall against Giardia lamblia infection. The different morphological
      and immunohistochemical results in the duodenum of children with giardiasis can
      elucidate a variety of clinical symptoms from asymptomatic to severe infection.

PMID- 20675274
TI  - Immunoreactivity of ATF-2 and Fra-2 in human dental follicle.
AB  - It is asserted that epithelial rests in dental follicle (DF) existing around the
      impacted teeth in adults are effective in cyst formation. In this study, it is
      intended for determining and comparing the immunoreactivity (IR) ratio of ATF-2
      and Fra-2 proteins, the members of Activator Protein-1 (AP-1) family which
      regulates important cellular activities such as growth, proliferation and
      differentiation, in DF epithelial cells (EC) and connective tissue cells (CC). In
      this study, ATF-2 and Fra-2 immunoreactivity (ATF-2-IR and Fra-2-IR) in EC and CC
      in DF tissues obtained from 30 patients were analyzed by using
      immunohistochemical method. Ratios of ATF-2-IR positive cells were found 17.36+/
      9.55% in EC, 27.27+/-14.86% in CC and ratios of Fra-2-IR positive cells were
      found 20.04+/-11.47% in EC, 16.71+/-9.05% in CC. In the statistically comparison
      performed; significant differences were found between EC and CC in terms of both
      ATF-2-IR (p<0.001) and Fra-2-IR (p<0.05). In EC, no significant difference was
      found between ATF-2-IR and Fra-2-IR (p>0.05), whereas significant difference was
      found between ATF-2-IR and Fra-2-IR in CC (p<0.001). According to these data, it
      can be suggested that Fra-2 protein may be more effective than ATF-2 protein in
      cyst formation originated from EC of DF. Besides, finding that ATF-2-IR and Fra-2
      IR are different in CC although similar in EC shows that AP-1 members can be
      expressed at different ratios in same tissues.

PMID- 20675275
TI  - The estimation of oxidative stress markers and apoptosis in right atrium auricles
      cardiomyocytes of patients undergoing surgical heart revascularisation with the
      use of warm blood cardioplegia.
AB  - Oxidative stress markers and apoptosis were estimated during elective surgical
      heart revascularization. Eight patients with good ejection fraction underwent
      coronary artery bypass grafting (CABG) with the use of warm blood cardioplegia.
      Two right atrium auricle biopsy specimens were collected before and after the
      operation. Specimens underwent immunocytochemical analysis of mitochondrial
      manganese superoxide dismutase (MnSOD) expression and apoptosis estimation by the
      TUNEL method. Ultrastructure analysis under electron microscope was made.
      Satisfactory results of the operation were obtained. After CABG the MnSOD
      expression increase in sections of auricles was observed through the increase of
      stain intensity and the percentage of cells with positive stain (from 30 to 80%).
      The apoptotic cells percentage remained at approximately the same level. Under
      the electron microscope insignificant pathological changes were observed. On this
      basis one may assume that in the case of cardiosurgical procedures with short
      aorta cross-clamping time and low operation risk level the application of
      cardioplegia sufficiently prevents reactive oxygen forms (ROF) cytotoxic activity
      although it does not inhibit the expression of oxidative stress (OS) markers. In
      our opinion the method of examining right atrium sections is safe and provides
      results comparable with other publications. It may also be a voice in the
      discussion on new methods of heart protection during cardiac surgery procedures.

PMID- 20675276
TI  - Changes in vasoactive intestinal peptide, pituitary adenylate cyclase-activating
      polypeptide and neuropeptide Y-ergic structures of the enteric nervous system in
      the carcinoma of the human large intestine.
AB  - This investigation was aimed at immunohistochemical analysis of potential changes
      in the enteric nervous system caused by cancer of the large intestine. In this
      purpose, neurons and nerve fibers of intestinal plexuses containing
      neuropeptides: vasoactive intestinal peptide (VIP), pituitary adenylate cyclase
      activating polypeptide (PACAP) and neuropeptide Y (NPY), in pathologically
      changed part of the large intestine were microscpically observed and compared.
      Samples were taken from patients operated due to cancer of the sigmoid colon and
      rectum. The number of neurons and density of nerve fibres containing
      neuropeptides found in sections with cancer tissues were compared to those
      observed in sections from the uninvolved intestinal wall. Changes relating to
      reductions in the number of NPY-ergic neurons and density of nerve fibres in
      submucous and myenteric plexuses in the sections with cancer tissues
      (pathological sections) were statistically significant. A statistically similar
      presence of VIP-ergic and PACAP-ergic neurons in the submucosal and myenteric
      plexuses was observed in both the pathological and control sections. On the other
      hand, in the pathological sections, VIP-ergic nerve fibres in the myenteric
      plexuses and PACAP-ergic nerve fibres in the submucosal and myenteric plexuses
      were found to be less dense. Analysis revealed changes in pathologically affected
      part of the large intestine may caused disruption of proper intestinal function.
      Observed changes in the neural elements which are responsible for relaxation of
      the intestine may suggest dysfunction in the innervation of this part of the
      colon.

PMID- 20675277
TI  - Cytology of nasal mucosa, olfactometry and rhinomanometry in patients after CO2
      laser mucotomy in inferior turbinate hypertrophy.
AB  - To evaluate the cytology of nasal mucosa and sense of smell and nasal patency in
      patients underwent carbon dioxide laser turbinoplasty (CO2 laser mucotomy) due to
      chronic nasal hypertrophy. 46 patients with inferior turbinate hypertrophy
      underwent complete laryngological examination, anterior rhinomanometry, olfactory
      measurements and cytology of nasal mucous which were performed before and 3
      months after CO2 laser mucotomy. Laser mucotomy was performed under local
      anesthesia. Cytograms revealed significant changes in cell proportion before and
      after the surgery. Goblet cells predominated in nasal smears before the laser
      mucotomy. An average percentage of eosinophils in evaluated cytograms before the
      surgery was 2.1%. Three months after laser mucotomy we observed decrease in
      goblet cells proportion (the mean range of goblet cells was 16.4%) in nasal
      cytology. We have also observed improvement in olfactory function, however only
      in 7 patients (20.6%). The mean value of total nasal airway resistance (NAR)
      before treatment was 0.98+/-0.24 Pa/cm3/s at 75 Pa. Rhinomanometry after 3 months
      showed a reduction in mean total resistance from the pretreatment level to 0.77
      Pa/cm3/s. We believe that CO2 laser mucotomy is an efficacious, minimally
      invasive and easy to use treatment of inferior turbinate hypertrophy which is
      performed under local anesthesia with little discomfort for the patient and does
      not require hospitalization.

PMID- 20675278
TI  - Antiproliferative and pro-apoptotic effects of quercetin on human pancreatic
      carcinoma cell lines EPP85-181P and EPP85-181RDB.
AB  - Polyphenols are present in several edible plants and for many years induce high
      interest mainly due to their antioxidative and anti-inflammatory influence. At
      present, numerous studies are conducted on antineoplastic effects of the
      compounds. One of most effective biopolyphenols involves the flavonol quercetin.
      Our studies aimed at evaluation of antiproliferative and pro-apoptotic effects of
      quercetin alone and in combinations with daunorubicin on cells of human
      pancreatic carcinoma lines. The experiments were conducted on two cell lines,
      sensitive to daunorubicin EPP85-181P line, and its resistant variant EPP85
      181RDB. Effect of studied substances on cell proliferation was detected using
      sulphorhodamine B (SRB) protein staining method. Apoptotic damage was estimated
      using comet and TUNEL techniques. Our data demonstrated that quercetin exerted
      cytotoxic action on cells of the both neoplastic cell lines in concentration
      dependent manner. In the case of EPP85-181RDB cell line, quercetin seemed to
      sensitize resistant cells to daunorubicin. In parallel, the effect of both
      substances on the sensitive cell line was synergistic. Results of the studies
      confirmed that quercetin may probably break resistance of neoplastic cells to
      chemotherapy. On the other side, studied flavonol augmented action of cytostatic
      drug in case of sensitive tumour cells what suggest, that it might allow to
      decrease dosage of cytostatic drugs and reduce negative side effects of the
      treatment.

PMID- 20675279
TI  - The endothelial cell markers von Willebrand Factor (vWF), CD31 and CD34 are lost
      in glomerulonephritis and no longer correlate with the morphological indices of
      glomerular sclerosis, interstitial fibrosis, activity and chronicity.
AB  - Endothelial cells (ECs) are active participants of an inflammatory process in
      glomeruli. EC damage has been shown to play an important role in the progression
      of glomerulonephritis (GN). The degree of glomerular and peritubular capillary
      loss in models of progressive renal disease correlates with the severity of
      glomerulosclerosis and interstitial fibrosis. The aim of our study was to analyze
      the association of vWF, CD31 and CD34 immunoreactivity with the morphological
      indices of glomerular sclerosis, interstitial fibrosis, activity and chronicity
      in GN. A cross-sectional study of 22 patients with GN was conducted. Conventional
      stains (hematoxylin-eosin, periodic acid Schiff and Trichrome Gomori stains) and
      immunohistochemistry (vWF, CD31 and CD34) were employed on kidney biopsies.
      Activity and chronicity of GN, as well as glomerular segmental sclerosis and
      interstitial fibrosis, were evaluated according to a scoring system initially
      used for lupus nephritis and antineutrophil-cytoplasmic-antibody-associated
      vasculitis. Immunohistochemistry was assessed using a semi-quantitative score.
      Statistical analysis was performed using EpiInfo 6.04. The mean patient age was
      46.68+/-14.09; 14 patients were male, and eight were female. Performing
      Spearman's rank correlation test, no correlation was found between each marker
      and glomerular segmental sclerosis, interstitial fibrosis, activity and
      chronicity, which suggests a loss of these markers and microvasculature
      involvement.

PMID- 20675280
TI  - Evaluation of distant results after lamivudine discontinuation in children with
      chronic hepatitis B.
AB  - The aim of this study was to estimate distant results after discontinuation of
      long term lamivudine treatment in children with chronic hepatitis B. Furthermore,
      the emergence of HBV polymerase gene variants in YMDD motif during therapy was
      examined. Additionally, the most commonly occurring type of mutation in the
      polymerase YMDD region were investigated. The study involved 27 HBeAg positive
      children with chronic hepatitis B. Children included to lamivudine therapy were
      previously treated without effects with interferon alpha.

PMID- 20675281
TI  - Correlation between metallothionein (MT) expression and selected prognostic
      factors in ductal breast cancers.
AB  - Our study aimed at examining significance of metallothionein (MT) expression in
      ductal breast cancers by determination of a relationship between expression of MT
      protein (MT-1/2) and selected prognostic factors, including grade of histological
      differentiation (G), expression of Ki-67 proliferative antigen, expression of
      estrogen receptors (ER) and progesterone receptors (PgR) and expression of HER-2
      receptor. Material for the studies involved 54 samples of invasive ductal breast
      cancer, manifesting malignancy grades of G1-G3. In paraffin sections of examined
      tumours immunohistochemical reactions were performed using specific antibodies
      directed to MT, Ki-67, ER, PgR or HER-2. Intensity of MT-specific
      immunohistochemical reactions was measured using the semiquantitative IRS scale
      of Remmele. Intensity of colour reactions targeted at Ki-67, ER, PgR was
      evaluated scoring proportions of positive cells, while HER-2-specific reactions
      were evaluated in the scale of 0-3 points. The lowest level of MT expression was
      detected in breast cancer cases of G1 malignancy grade (G1 vs G3 p=0.020). A
      positive correlation between MT and Ki-67 antigen expression (r=0.32, p=0.019)
      was disclosed. Moreover, MT expression exhibited negative correlations with
      expression of ER (r=-0.35, p=0.008) and PgR (r=-0.27, p=0.046). No relationships
      could be detected between expression of MT and expression of HER-2 (r=0.12,
      p=0.37). The obtained results suggest that MT expression might be helpful in
      prognostic evaluation of ductal breast cancers.

PMID- 20675282
TI  - Prognostic value of CA 19-9 level in resectable pancreatic adenocarcinoma.
AB  - The prognosis in patients with pancreatic cancer is poor and some authors
      describe it as a lethal disease. At the time of diagnosis only 14% of patients
      could be surgically treated and up to 30% of them die within 12 months.
      Therefore, further clinical investigations on preoperative patient qualification
      are needed. A total of 81 patients were included into the study. The CA 19-9
      concentration was measured before surgery by an automated, commercially available
      enzyme immunoassay in Axsym analyzer (Abott Diagnostics Laboratory). A value of
      37 U/ml was used as the upper limit of normal levels. Tumors were staged
      according to the Union Against Cancer (UICC) of 2004 and graded during the
      histological evaluation according to the G0-G4 scale. All patients were monitored
      every three month via outpatient clinic visits. In the case of missing visit we
      contacted the families to establish the cause. We assessed perioperative, 12
      month, 2 year and 5 year survival. Twelve moth, 2 year and 5 year survival were
      assessed in the whole studied population and in the group of patients with the
      exception of these who died during the perioperative period. The total five year
      survival was 6%. The median time of survival was 467 days (range: 163 - 586
      days). The perioperative period was survived by 91.4% patients, 12 months were
      survived by 71.6% patients, 2 years were survived by 35.8% patients, 5 years were
      survived by 6.2% patients. The serum Ca 19-9 level was above the normal limit in
      80.5% patients. ROC curve analysis revealed that CA 19-9 level of more than 106
      U/ml was linked to 2 year survival with 79.3% sensitivity and 74.5% specificity.
      Preoperative level of CA 19-9 below 106U/ml represents a predictive factor of 2-
      and 5-year survival, independent of other factors, such as lower size of the
      tumor, absence of metastases to lymph nodes, female gender of patients. After
      exclusion of the patients who died in the perioperative period, no relationship
      could have been disclosed between preoperative CA 19-9 levels and one year
      survival. The observation points to the chance that patients with higher levels
      of CA 19-9 harbour micrometastases, the development of which is sufficiently slow
      to allow for a one-year survival of the patients but which increase the risk of
      death after two and five years.

PMID- 20675283
TI  - A comparative study of the protein C system in mother's blood, cord blood and
      amniotic fluid.
AB  - Activated protein C (APC) is an important anticoagulant which plays a role in
      pathophysiology of pregnancy, e.g. in maintenance of the uteroplacental
      circulation and development of the fetus as well as in pathogenesis of
      preeclampsia. The study objective was to compare the levels of the respective
      components of the protein C system (protein C, PC; protein S, PS; thrombomodulin,
      TM) as well as thrombin activatable fibrinolysis inhibitor - TAFI in mother's
      blood, cord blood and amniotic fluid. The study group consisted of 136 healthy
      parturients at term, divided into subgroups of 30-35. The immunoenzymatic method
      (ELISA) was used to measure the antigens of the components studied. The
      concentrations of PC and PS antigens were the highest in the mother's blood
      plasma (135.11+/-1.05% and 92.0+/-13.24%, respectively), lower in cord blood
      plasma (57.60+/-10.32% and 33.19+/-4.96%, respectively) and the lowest in
      amniotic fluid (6.75+/-3.50% and 2.40+/-1.64%, respectively); the differences
      between the levels of that of mother, fetus and amniotic fluid were statistically
      significant (p< or =0.0001). The TM and TAFI antigen concentrations were the
      highest in cord blood plasma (11.35+/-3.71 ng/ml and 91.50 (median; range: 71.76
      160.77) ng/ml, respectively) and lower in maternal plasma (4.51+/-0.71 ng/ml and
      55.46 - median; range: 39.77-68.54 ng/ml, respectively); the differences between
      the levels of that of cord blood plasma and maternal plasma were statistically
      significant (p< or =0.0001). Of the three protein C system components, PC and PS
      occur in relatively high concentrations in maternal blood, being lower in fetal
      blood and the lowest in amniotic fluid. On the other hand, as an exception, the
      concentrations of TM and TAFI are the highest in fetus blood.

PMID- 20675284
TI  - Pathological findings in cornea tissue of patients with penetrating keratoplasty.
AB  - The aim of this clinical study was to examine corneas extracted from the patients
      during penetrating keratoplasty for the presence of immunoglobulins and
      inflammatory cells that can be warning for the graft failure. Individual clinical
      diagnoses were correlated to the presence of the inflammatory signs in corneal
      tissue. The signs of inflammation in corneal layers were detected especially in
      group of patients classified as viral keratitis but were also found in corneas of
      patients with degenerative diseases of the cornea. Depending on the number of
      keratoplasties no statistical difference in analysed parameters was found.
      Inflammatory process represented by slight positive presence cellular
      infiltration and/or immunoglobulins could be present in corneal tissue also in
      absence of acute manifestation. Histological and immunohistochemical evaluation
      of corneal tissue from patients undergoing penetrating keratoplasty could improve
      estimation of correct diagnosis. Subsequently prompt adequate therapy could
      improve worse prognosis of corneal graft with evident immune process.

PMID- 20675285
TI  - Changes in thickness of each layer of developing chicken cornea after
      administration of caffeine.
AB  - The aim of the study was the presentation of changes in thickness of each layer
      of a developing cornea, that came into being under an influence of caffeine which
      was administered to chicken embryos. Research materials were 26 chicken embryos
      from breeding eggs that had been incubated. Breeding eggs were divided into two
      groups: control (n=30) in which Ringer liquid was given, and experimental (n=30)
      in which teratogenic dose of caffeine was administrated - 3.5 mg/egg. In 36th
      hour of incubation solutions were given with cannula through a hole in an egg
      shell directly onto amniotic membrane. After closing the hole with paraffin, eggs
      were put back into incubator. On 10th and 19th day of incubation corneas were
      taken for morphometric and morphological analysis. In experimental groups
      reduction of corneal thickness, thickening of corneal epithelium and corneal
      endothelium as well as Bowman's and Descemet's membranes, decrease of thickness
      of corneal stroma in comparison with the control group have been observed.
      Caffeine causes thickness changes of all layers and decreases the total thickness
      of a developing cornea.

PMID- 20675286
TI  - Melatonin modulates the effects of diethylstilbestrol (DES) on the anterior
      pituitary of the female Wistar rat.
AB  - We studied the anti-tumorigenic effect of melatonin in diethylstilbestrol (DES)
      treated anterior pituitaries in rats. Twenty-one female Wistar rats were randomly
      allocated into three groups: vehicle control rats, DES-treated rats, and DES
      treated rats co-administrated with melatonin beginning at week 13. At the end of
      16 weeks, rats were weighed and decapitated for morphological studies, including
      an H+E staining-based score evaluation in regard to cell proliferation,
      angiogenesis, immunostaining for VEGF, MMP-9, and AQP-1, and electron microscopy.
      Compared with vehicle, long-term treatment of DES significantly reduced rat body
      weight and increased H+E score, both of which were counteracted by melatonin.
      Administration of melatonin also reduced the expression of VEGF and MMP-9,
      although no changes were detected in AQP-1 expression. In rats cotreated with
      melatonin, the RER loosened and accumulated more secretion granules. We thus
      concluded that melatonin can modulate the effects of DES on the rat anterior
      pituitary by downregulating expression of VEGF and MMP-9 and suppressing the
      release of secretion granules, suggesting a therapeutic potential in estrogen
      induced pituitary malfunctions.

PMID- 20675287
TI  - TGF-beta1 immunohistochemistry and promoter methylation in chronic renal failure
      rats treated with Uremic Clearance Granules.
AB  - The aim of the study was the explain the mechanism related to therapeutic effects
      of Uremic Clearance Granules (Niaoduqing Keli in Chinese) on adenine-induced
      Chronic Renal Failure in rats. Thirty 8-week-old male Wistar rats were selected
      and randomly divided in to 3 groups: Normal Control Group (NCG)consisted of 10
      rats, Chronic Renal Failure Pathological Control Group (PCG) 10 rats, and Uremic
      Clearance Granules Treatment Group (UCG) 10 rats. Each rat in PCG and UCG was fed
      with adenine-enriched diets, containing 10 g adenine per kg food for 6 weeks.
      After fed with adenine, each rat in UCG was administered orally with 2 ml
      solution of Uremic Clearance Granules for 6 weeks. The concentration of Uremic
      Clearance Granules solution was 0.42 g/ml which was 10 times of human. On days 42
      and 84, the serum levels of creatinine, Blood Urea Nitrogen and homocysteine were
      determined. The methylation of TGFbeta1 promoter was tested by methylation
      specific PCR. TGF-beta1 mRNA and protein expression in rat renal cortex were
      analyzed by real-time RT-PCR and Immunohistochemistry. (1) Experimented on model
      of Chronic Renal Failure in rats, the preparation was proved to be able to reduce
      serum creatinine, Blood Urea Nitrogen, and homocysteine (p<0.05), improve renal
      function. (2) The expression of TGF-beta1 in mRNA and protein level were down
      regulated. (3) TGF-beta1 promoter was demethylated at some loci in PCG, and was
      recovered in UCG. After treatment with Uremic Clearance Granules, the Chronic
      Renal Failure Wistar rat's kidney function was recovered. The recovery may be
      result of the remethylation of TGF-beta1 promoter and then lead to TGF-beta1 be
      transcripted and translated normally. The experimental study explain the
      molecular mechanism by which Uremic Clearance Granules treat Chronic Renal
      Failure.

PMID- 20675288
TI  - Interactions of egg yolk lipoprotein fraction with boar spermatozoa assessed with
      a fluorescent membrane probe.
AB  - The interactions of a fluorescent membrane probe, 1-anilinonaphthalene-8-sulfonic
      acid (1,8-ANS), with boar spermatozoa were followed through the use of
      lipoprotein fraction of ostrich egg yolk (LPFo). Semen samples, extended in
      Kortowo 3 (K3) extender, were supplemented with 2% or 5% LPFo and stored for 3h
      at 16 degrees C. Additionally, cold shock-treated spermatozoa (1h at 4 degrees C)
      were stored in K3 extender supplemented with LPFo for 3h at 16 degrees C. In each
      boar, the fluorescent enhancement of ANS was observed in K3-extended semen
      supplemented with LPFo, prior to storage. Following storage, there was a
      significant increase in LPFo-ANS fluorescence, particularly in the sperm membrane
      overlying the head and midpiece regions. There were significant differences among
      the boars with respect to the sperm populations defined by the LPFo-ANS
      fluorescence. Sperm viability was not significantly affected during the storage
      period. Furthermore, the proportions of spermatozoa defined by the different
      patterns of LPFo-ANS fluorescence were low and remained unchanged after storage
      of cold shock-treated spermatozoa with 2% or 5% LPFo, suggesting irreversible
      damage to the sperm membrane architecture. These findings indicate that the ANS
      fluorescent probe could be used to shed more light on the nature of the
      interactions between LPFo and sperm membrane following semen preservation. Such
      valuable information could contribute to the development of an optimal protocol
      for cryopreservation of boar semen.

PMID- 20675289
TI  - Effects of maternal deprivation on the somatotrophic axis and neuropeptide Y in
      the hypothalamus and pituitary in female lambs. The histomorphometric study.
AB  - The effects of maternal deprivation on the somatotrophic axis and neuropeptide Y
      (NPY) neuronal system in the hypothalamus of female lambs were evaluated. Twelve
      week-old lambs were divided into two groups: the control (lambs stayed with
      mothers) and maternally deprived (MD; lambs separated for 3 days from mothers).
      The expression of immunoreactive (ir) somatostatin in the neurons of the
      periventricular nucleus (PEV) and in nerve terminals of the median eminence (ME),
      growth hormone (GH) in the adenohypophyseal cells and NPY in the neurons of the
      PEV and arcuate (ARC) nuclei of the hypothalamus using immunohistochemistry
      followed by the image analysis were estimated. Concentrations of GH in the blood
      plasma were determined by radioimmunoassay. The expression of ir somatostatin in
      the PEV and ME, ir NPY in the ARC and PEV, ir GH in adenohypophyseal cells, and
      blood plasma GH concentrations were greater (p<0.05) in MD than in the control
      lambs. In conclusion, MD affects the somatotrophic axis by enhancement of GH
      secretion via restraining of somatostatin output. The simultaneous increase of
      expression of hypothalamic ir NPY suggests NPY involvement in the regulation of
      psychoemotional stress through the somatotrophic axis in the female lambs.

PMID- 20675290
TI  - Immunolocalization of PTHrP in the parotid glands of three rodents species:
      Clethrionomys glareoulus, Microtus arvalis and white Swiss mice.
AB  - The current study was inspired by the fact that since 2004 no report had appeared
      on the occurrence of this peptide in healthy parotid glands of humans and
      animals. The objective of the current study was to investigate the
      immunolocalization of PTHrP in the parotid gland of three male rodents: 6 common
      voles (Microtus arvalis, Pallas, 1779), 6 bank voles (Clethrionomys glareoulus,
      Schreber, 1780) and 6 white Swiss mice, as well as to find out any species
      differences in the distribution of this peptide in various types of cells of the
      parotid gland. Immunocytochemical reactions were performed using the ABC
      technique with specific rabbit antibodies against human PTHrP (34-53)
      (CALBIOCHEM), diluted 1:70 and 1:50. We observed positive PTHrP expression in the
      epithelial cells of the striated duct in all the three animal species. The
      expression was strong in white mouse and very strong in common vole and bank
      vole. In all the rodent species studied, the reaction for PTHrP was granular in
      nature and irregularly distributed in the cytoplasm, being definitely stronger at
      the base and weaker at the apex of the cells. The PTHrP expression was negative
      in the epithelium of the intercalated duct, interlobular duct, main excretory
      duct, as well as in the myoepithelial cells surrounding the excretory ducts or
      serous acini.

PMID- 20675291
TI  - Antifungal activity of triterpenoid isolated from Azima tetracantha leaves.
AB  - The present study was designed to evaluate the antifungal activity of Azima
      tetracantha extracts and isolated compound (friedelin) against fungi. Antifungal
      activity was carried out using broth microdilution method and fractions were
      collected using (silica gel) column chromatography. The antifungal activity of
      Azima tetracantha crude extracts and isolated compound (friedelin) were evaluated
      using the micro dilution method. Hexane extract showed some antifungal activity.
      The compound also exhibited antifungal activity against tested fungi. The lowest
      MIC against Trichophyton rubrum (296) was 62.5 microg/ml and the MIC for
      Curvularia lunata was 62.5 microg/ml. These results suggest that Friedelin is a
      promising antifungal agent.

PMID- 20675292
TI  - Information-seeking at a caregiving website: a qualitative analysis.
AB  - BACKGROUND: The Internet is widely used for health information, yet little is
      known about the online activity of family caregivers of elders, a rapidly growing
      group. In order to better understand the online information-seeking activity of
      "e-caregivers" and other visitors at a caregiving website, we undertook a
      qualitative analysis of survey data from a website marketed as a comprehensive
      resource for adults caring for aging parents. OBJECTIVE: The objectives were to
      better understand what types of information are sought by those visiting a
      website focused on elder-care issues and to identify overarching themes that
      might inform future development of Internet resources related to caregiving and
      aging. METHODS: From March 2008 to March 2009, a 5-question pop-up survey was
      offered 9662 times and completed 2161 times. For 1838 respondents, included was a
      free text answer to the question "What were you looking for?" and 1467 offered
      relevant and detailed responses. The survey also asked about satisfaction with
      the site, gender of the respondent, and relationship to the individual being
      cared for. Content analysis was used to develop a coding dictionary, to code
      responses into information-seeking categories, and to identify overarching
      themes. RESULTS: Of the respondents (76% of whom were female), 50% indicated they
      were caring for parents, 17% for themselves only, and 31% for others. Over half
      (57%) reported finding what they were looking for, and 46% stated they were
      extremely likely to recommend the website. Frequently mentioned information
      seeking categories included "health information," "practical caregiving," and
      "support." Respondents also requested information related to housing, legal,
      insurance, and financial issues. Many responses referred to multiple comorbid
      conditions and complex caregiving situations. Overarching themes included (1) a
      desire for assistance with a wide range of practical skills and information and
      (2) help interpreting symptoms and behavior, such as knowing what life impacts to
      expect over the course of a health condition or treatment. CONCLUSION: Visitors
      to a website targeting adults caring for aging parents reported seeking both
      general information on caregiving and specific assistance with the complex
      custodial, medical, emotional, and financial aspects of caregiving. Visitors
      requested both information to build caregiving skills as well as assistance in
      interpreting and knowing what to expect from symptoms, health conditions, and
      changes in behavior and relationships. Many desired communication with and
      support from other caregivers. Health care providers and eHealth developers
      should expect that many caregivers of elders are using the Internet as a
      resource. Further research and development is needed to fully realize the
      Internet's potential for education and support of caregivers.

PMID- 20675293
TI  - Usability testing of an online self-management program for adolescents with
      juvenile idiopathic arthritis.
AB  - BACKGROUND: A new bilingual (English and French) Internet-based self-management
      program, Teens Taking Charge: Managing Arthritis Online, for adolescents with
      arthritis and their parents was developed following a needs assessment.
      OBJECTIVES: This study explored the usability (user performance and satisfaction)
      of the self-management program for youth with juvenile idiopathic arthritis (JIA)
      and their parents to refine the health portal prototype. METHODS: A qualitative
      study design with semi-structured, audio taped interviews and observation by a
      trained observer was undertaken with two iterative cycles to determine the
      usability (ease of use, efficiency, errors, and user satisfaction) of the user
      interface and content areas of the intervention. A purposive sample of English
      speaking (n = 11; mean age = 15.4, standard deviation [SD] 1.7) and French
      speaking (n = 8; mean age = 16.0, SD 1.2) adolescents with JIA and one of their
      respective parents/caregivers were recruited from 2 Canadian tertiary care
      centers. Descriptive statistics and simple content analyses were used to organize
      data into categories that reflected the emerging usability themes. RESULTS: All
      of the participants had access to a computer/Internet at home; however,
      adolescents were more comfortable using the computer/Internet than their parents.
      Adolescents and parents provided similar as well as differing suggestions on how
      the website user interface could be improved in terms of its usability
      (navigation; presentation and control usage errors; format and layout; as well as
      areas for further content development). There were no major differences in
      usability issues between English- and French-speaking participants. Minor changes
      to the website user interface were made and tested in a second cycle of
      participants. No further usability problems were identified in the second
      iterative cycle of testing. Teens and parents responded positively to the
      appearance and theme of the website (ie, promoting self-management) and felt that
      it was easy to navigate, use, and understand. Participants felt that the content
      was appropriate and geared to meet the unique needs of adolescents with JIA and
      their parents as well as English- and French-speaking families. Many participants
      responded that the interactive features (discussion board, stories of hope, and
      video clips of youth with JIA) made them feel supported and "not alone" in their
      illness. CONCLUSIONS: We describe the usability testing of a self-management
      health portal designed for English- and French-speaking youth with arthritis and
      their parents, which uncovered several usability issues. Usability testing is a
      crucial step in the development of self-management health portals to ensure that
      the various end users (youth and parents) have the ability to access, understand,
      and use health-related information and services that are delivered via the
      Internet and that they are delivered in an efficient, effective, satisfying, and
      culturally competent manner.

PMID- 20675294
TI  - Channeling and conformational changes in the heterotetrameric sarcosine oxidase
      from Corynebacterium sp. U-96.
AB  - We characterized the crystal structures of heterotetrameric sarcosine oxidase
      (SO) from Corynebacterium sp. U-96 complexed with methylthioacetate (MTA),
      pyrrole 2-carboxylate (PCA) and sulphite, and of sarcosine-reduced SO. SO
      comprises alpha-, beta-, gamma- and delta-subunits; FAD and FMN cofactors; and a
      large internal cavity. MTA and PCA are sandwiched between the re-face of the FAD
      isoalloxazine ring and the beta-subunit C-terminal residues. Reduction of flavin
      cofactors shifts the beta-subunit Ala1 towards the alpha-subunit Met55, forming a
      surface cavity at the oxygen-channel vestibule and rendering the beta-subunit C
      terminal residues mobile. We identified three channels connecting the cavity and
      the enzyme surface. Two of them exist in the inter-subunit space between alpha
      and beta-subunits, and the substrate sarcosine seems to enter the active site
      through either of these channels and reaches the re-side of the FAD isoalloxazine
      ring by traversing the mobile beta-subunit C-terminal residues. The third channel
      goes through the alpha-subunit and has a folinic acid-binding site, where the
      iminium intermediate is converted to Gly and either formaldehyde or, 5,10
      methylenetetrahydrofolate. Oxygen molecules are probably located on the surface
      cavity and diffuse to the FMN isoalloxazine ring; the H(2)O(2) formed exits via
      the oxygen channel.

PMID- 20675295
TI  - A novel laccase with urate oxidation activity from Lysobacter sp. T-15.
AB  - A unique urate-oxidizing enzyme was identified in a bacterium, strain T-15. Based
      on its phylogenetic, physiological and biochemical properties, strain T-15 was
      deemed to be a novel species within the genus Lysobacter. The enzyme expressed in
      Lysobacter sp. T-15 was composed of 592 amino acids and contained four consensus
      copper-binding sites, and the recombinant enzyme was, at least in this study,
      speculated to have three Cu ions per subunit. The primary structure of the enzyme
      was 33% identical to Marinomonas mediterranea polyphenol oxidase, but it showed
      no significant similarity to any known urate oxidase. With urate as the
      substrate, the catalytic efficiency (k(cat)/K(m)) of recombinant enzyme was 4.0 *
      10(2) s(-)(1)mM(-)(1), and it was not inhibited by xanthine, a strong urate
      oxidase inhibitor. The enzyme also showed activity toward 2,2'-azino-bis-(3
      ethylbenzothiazoline-6-sulphonic acid), 2,6-dimethoxyphenol and bilirubin, with
      catalytic efficiencies of 4.9 * 10(2), 1.1 * 10(2) and 3.6 * 10(3) s(-)(1)mM(
      )(1), respectively. We deemed the enzyme would be a member of laccase from its
      broad substrate specificity. However, typical laccase and other multi-copper
      oxidases such as bilirubin oxidase and ascorbate oxidase seldom exhibit urate
      oxidation activity. These results would expand the laccase substrate range to
      include urate.

PMID- 20675296
TI  - Invited commentary.

PMID- 20675297
TI  - On "Physical therapists make accurate and appropriate discharge
      recommendations..." Smith BA, Fields CJ, Fernandez N. Phys Ther. 2010;90:693-703.

PMID- 20675298
TI  - Expansion of human cardiac stem cells in physiological oxygen improves cell
      production efficiency and potency for myocardial repair.
AB  - AIMS: the ex vivo expansion of cardiac stem cells from minimally invasive human
      heart biopsies yields tens of millions of cells within 3-4 weeks, but chromosomal
      abnormalities were frequently detected in preliminary production runs. Here we
      attempt to avoid aneuploidy and improve cell quality by expanding human cardiac
      stem cells in physiological low-oxygen (5% O(2)) conditions, rather than in
      traditional culture in a general CO(2) incubator (20% O(2)). METHODS AND RESULTS:
      human heart biopsies (n = 16) were divided and processed in parallel to expand
      cardiac stem cells under 5% or 20% O(2). Compared with 20% O(2), 5% O(2) culture
      doubled the cell production and markedly diminished the frequency of aneuploidy.
      Cells expanded in 5% O(2) showed lower intracellular levels of reactive oxygen
      species, less cell senescence, and higher resistance to oxidative stress than
      those grown in 20% O(2), although the expression of stem cell antigens and
      adhesion molecules was comparable between groups, as was the paracrine secretion
      of growth factors into conditioned media. In vivo, the implantation of 5% O(2)
      cells into infarcted hearts of mice resulted in greater cell engraftment and
      better functional recovery than with conventionally cultured cells. CONCLUSION:
      the expansion of human adult cardiac stem cells in low oxygen increased cell
      yield, and the resulting cells were superior by various key in vitro and in vivo
      metrics of cell quality. Physiological oxygen tensions in culture facilitate the
      ex vivo expansion of healthy, biologically potent stem cells.

PMID- 20675299
TI  - Tolerability of prolonged linezolid therapy in bone and joint infection:
      protective effect of rifampicin on the occurrence of anaemia?
AB  - BACKGROUND: Linezolid therapy has shown high rates of clinical success in
      patients with osteomyelitis and prosthetic joint infections caused by Gram
      positive cocci. Recent studies have demonstrated that linezolid/rifampicin
      combination therapy prevents the emergence of rifampicin-resistant mutations in
      vitro. However, linezolid/rifampicin combination-related haematological and
      neurological toxicities have not been evaluated. OBJECTIVES: To assess the
      tolerability of prolonged linezolid/rifampicin combination therapy compared with
      other linezolid-containing regimens in patients with bone and joint infections.
      METHODS: We reviewed the medical records of 94 patients who had received
      linezolid for >4 weeks after bone and joint infections. Anaemia was defined as a
      >=2 g/dL reduction in haemoglobin, leucopenia as a total leucocyte count <4 *
      10(9)/L, and thrombocytopenia as a reduction in platelet count to <75% of
      baseline. RESULTS: Anaemia was less frequent among patients on
      linezolid/rifampicin combination therapy than among patients on linezolid alone
      or in combination with other drugs (9.3%, 44% and 52%, respectively; P<0.01). In
      multivariate analysis, age and treatment group were independently associated with
      anaemia. Thrombocytopenia was reported in 44% of patients on linezolid/rifampicin
      combination therapy, in 48% of patients on linezolid alone and in 57.7% of
      patients on other linezolid-containing regimens. Age was the only variable
      associated with thrombocytopenia (P=0.019) in univariate analysis. CONCLUSIONS:
      Linezolid/rifampicin combination therapy was associated with a significantly
      reduced incidence of anaemia among patients with bone and joint infections, but
      it did not have an effect on thrombocytopenia and peripheral neuropathy rates.
      Linezolid/rifampicin combination therapy was not associated with poor clinical
      outcomes.

PMID- 20675300
TI  - Lack of leptin activity in blood samples of Adelie penguin and bar-tailed godwit.
AB  - Unsuccessful attempts to identify the leptin gene in birds are well documented,
      despite the characterization of its receptor (LEPR). Since leptin and LEPR have
      poor sequence conservation among vertebrates, we speculated that a functional
      assay should represent the best way to detect leptin in birds. Using a leptin
      bioassay that is based on activation of the chicken LEPR in cultured cells, blood
      samples from wild birds with extreme seasonal variation in voluntary food intake
      and fat deposition (Adelie penguins and bar-tailed godwits) were tested for
      leptin activity. In these experiments, blood samples collected during the pre
      incubation and the chick-rearing periods of Adelie penguins, and during the
      migratory flight and refueling stages of bar-tailed godwits, were found to
      contain no detectable leptin activity, while the sensitivity of the assay to
      activation by human blood samples from donor subjects representing a variety of
      body mass indices and fat contents was clearly demonstrated. These results
      suggest that in birds, an alternative control mechanism to that of mammals
      operates in the communication between the body fat tissues and the central
      control on energy homeostasis.

PMID- 20675301
TI  - The differences in feeding-inhibitory responses to peripheral and central leptin
      between non-lactating and lactating rats.
AB  - This study was conducted to examine the contributions of central and peripheral
      leptin to hyperphagia in lactation. Lactating rats were mated at 7-8 weeks of age
      and housed singly with their litters. In experiment 1, food intakes were
      significantly (P<0.01) greater (350% on average) in lactation than in non
      lactation throughout a day. Cerebrospinal fluid (CSF) leptin levels remained
      constant despite plasma leptin levels being significantly (P<0.05) greater in non
      lactation than in lactation. In experiment 2, CSF leptin levels were not altered
      by i.v. injections of leptin (0.2 and 0.4 mg/kg body weight) despite that plasma
      leptin levels were dose dependently (P<0.01) increased. Moreover, i.v.
      administration of leptin significantly (P<0.05) decreased food intake in non
      lactating rats but not in lactating rats. In experiment 3, nocturnal food intakes
      were temporarily (P<0.05) reduced in non-lactating and lactating rats. I.c.v.
      administration of a leptin antagonist (15 MUg) blocked the reductions of food
      intakes. I.c.v. administration of leptin (10 MUg) significantly (P<0.05)
      decreased cumulative food intakes during 24 h in both the physiological states.
      In conclusion, this study has presented new evidence that the hyperphagia of
      lactating rats could be partly due to depressed sensitivity of neurons contacting
      blood leptin. In contrast, the responsiveness of leptin receptors contacting CSF
      leptin may not differ between non-lactating and lactating rats. Furthermore, the
      levels of CSF leptin remained constant independent of those of blood leptin.
      Therefore, the expression of hypothalamic leptin receptors contacting CSF could
      be involved in the difference in food intake between non-lactating and lactating
      rats.

PMID- 20675302
TI  - Peripubertal aromatase inhibition in male rats has adverse long-term effects on
      bone strength and growth and induces prostatic hyperplasia.
AB  - Aromatase inhibitors have been increasingly used in boys with growth retardation
      to prolong the duration of growth and increase final height. Multiple important
      roles of oestrogen in males point to potential adverse effects of this strategy.
      Although the deleterious effects of aromatase deficiency in early childhood and
      adulthood are well documented, there is limited information about the potential
      long-term adverse effects of peripubertal aromatase inhibition. To address this
      issue, we evaluated short-term and long-term effects of peripubertal aromatase
      inhibition in an animal model. Peripubertal male Wistar rats were treated with
      aromatase inhibitor letrozole or placebo and followed until adulthood. Letrozole
      treatment caused sustained reduction in bone strength and alteration in skeletal
      geometry, lowering of IGF1 levels, inhibition of growth resulting in
      significantly lower weight and length of treated animals and development of focal
      prostatic hyperplasia. Our observation of adverse long-term effects after
      peripubertal male rats were exposed to aromatase inhibitors highlights the need
      for further characterisation of long-term adverse effects of aromatase inhibitors
      in peripubertal boys before further widespread use is accepted. Furthermore, this
      suggests the need to develop more selective oestrogen inhibition strategies in
      order to inhibit oestrogen action on the growth plate, while beneficial effects
      in other tissues are preserved.

PMID- 20675303
TI  - Altered renal FGF23-mediated activity involving MAPK and Wnt: effects of the Hyp
      mutation.
AB  - Fibroblast growth factor-23 (FGF23), a hormone central to renal phosphate
      handling, is elevated in multiple hypophosphatemic disorders. Initial FGF23
      dependent Erk1/2 activity in the kidney localizes to the distal convoluted tubule
      (DCT) with the co-receptor alpha-Klotho (KL), distinct from Npt2a in proximal
      tubules (PT). The Hyp mouse model of X-linked hypophosphatemic rickets (XLH) is
      characterized by hypophosphatemia with increased Fgf23, and patients with XLH
      elevate FGF23 following combination therapy of phosphate and calcitriol. The
      molecular signaling underlying renal FGF23 activity, and whether these pathways
      are altered in hypophosphatemic disorders, is unknown. To examine Npt2a in vivo,
      mice were injected with FGF23. Initial p-Erk1/2 activity in the DCT occurred
      within 10 min; however, Npt2a protein was latently reduced in the PT at 30-60 
      min, and was independent of Npt2a mRNA changes. KL-null mice had no DCT p-Erk1/2
      staining following FGF23 delivery. Under basal conditions in Hyp mice, c-Fos and
      Egr1, markers of renal Fgf23 activity, were increased; however, KL mRNA was
      reduced 60% (P<0.05). Despite the prevailing hypophosphatemia and elevated Fgf23,
      FGF23 injections into Hyp mice activated p-Erk1/2 in the DCT. FGF23 injection
      also resulted in phospho-beta-catenin (p-beta-cat) co-localization with KL in
      wild-type mice, and Hyp mice demonstrated strong p-beta-cat staining under basal
      conditions, indicating potential crosstalk between mitogen-activated protein
      kinase and Wnt signaling. Collectively, these studies refine the mechanisms for
      FGF23 bioactivity, and demonstrate novel suppression of Wnt signaling in a KL
      dependent DCT-PT axis, which is likely altered in XLH. Finally, the current
      treatment of phosphate and calcitriol for hypophosphatemic disorders may increase
      FGF23 activity.

PMID- 20675304
TI  - Insulin treatment and high-fat diet feeding reduces the expression of three Tcf
      genes in rodent pancreas.
AB  - Specific single-nucleotide polymorphisms in intronic regions of human TCF7L2 are
      associated with an elevated risk of developing type 2 diabetes. Whether Tcf7l2 is
      expressed in pancreatic islets of rodent species at a considerable level,
      however, remains controversial. We used RT-PCR and quantitative RT-PCR to examine
      Tcf7l2 expression in rodent gut, pancreas, isolated pancreatic islets, and
      cultured cell lines. The expression level of Tcf7l2 was relatively lower in the
      pancreas compared to the gut or the pancreatic beta-cell line Ins-1.
      Immunostaining did not detect a Tcf7l2 signal in mouse pancreatic islets.
      Endogenous canonical Wnt activity was not appreciable in the pancreas of TOPGAL
      transgenic mice. Both Tcf7 and Tcf7l1, but not Lef1, were expressed in the
      pancreas. The expression of the three Tcf genes (Tcf7, Tcf7l1, and Tcf7l2) in the
      pancreas was reduced by treatment with insulin or high-fat diet feeding, in
      contrast to the stimulation of Tcf7l2 expression by insulin in the gut. We
      suggest that hyperinsulinemia represses Tcf gene expression in the pancreas.
      Whether and how this reduction alters the function of pancreatic beta cells
      during hyperinsulinemia deserves further investigation.

PMID- 20675305
TI  - Effects of adiponectin on human trophoblast invasion.
AB  - Adiponectin is an adipokine with insulin-sensitizing, anti-inflammatory, anti
      atherogenic, and anti-proliferative effects. The expression of specific
      adiponectin receptors in the placenta and in the endometrium suggests a role for
      this cytokine in placental development, but this role has not yet been
      elucidated. The invasion of trophoblast cells during the first trimester of
      pregnancy being crucial to placentation process, we have studied adiponectin
      effects on human trophoblast invasive capacities. We found that adiponectin
      stimulated human trophoblast cell migration in HTR-8/SVneo cells in a dose
      independent manner. In addition, adiponectin also significantly enhanced invasion
      of HTR-8/SVneo cells and of human extravillous trophoblast from first trimester
      placenta. These pro-invasive effects of adiponectin in human trophoblasts seem to
      be mediated in part via increased matrix metalloproteinases (MMP2 and MMP9)
      activities and via repression of TIMP2 mRNA expression. Our results suggest that
      adiponectin could be a positive regulator of the early invasion process by
      modulating the MMP/TIMP balance. Moreover, these results provide an insight into
      the role of adiponectin in pathological conditions characterized by insufficient
      or excessive trophoblast invasion.

PMID- 20675307
TI  - Adiponectin inhibits palmitate-induced apoptosis through suppression of reactive
      oxygen species in endothelial cells: involvement of cAMP/protein kinase A and AMP
      activated protein kinase.
AB  - The present study examined whether adiponectin can inhibit palmitate-induced
      apoptosis, and also the associated mechanisms and signal transduction pathways in
      human umbilical vein endothelial cells. Cells treated with 500 MUM palmitate for
      48 h increased reactive oxygen species (ROS) generation and induced apoptosis.
      Treatment with antioxidant N-acetyl-L-cysteine (1 mM) and globular adiponectin (5
      MUg/ml) inhibited palmitate-induced ROS generation and apoptosis. The AMP
      activated protein kinase (AMPK) activator 5-aminoimidazole-4-carboxamide-1-beta-D
      ribofuranoside (AICAR; 1 mM), and cAMP activators forskolin (10 MUM) and cholera
      toxin (200 ng/ml) also displayed the same effects. The inhibitory effects of
      adiponectin on ROS generation and apoptosis were reversed by the AMPK inhibitor
      compound C (40 MUM), cAMP inhibitor SQ22536 (50 MUM), and protein kinase A (PKA)
      inhibitor H-89 (10 MUM). The inhibitory effect of forskolin on palmitate-induced
      apoptosis was reversed by compound C, whereas the inhibitory effect of AICAR was
      not reversed by SQ22536 and H-89. AICAR and forskolin could not inhibit palmitate
      induced apoptosis in cells treated with dominant-negative AMPK. Forskolin
      increased phosphorylated AMPK at both Thr-172 and Ser-485/491. These results
      suggest that adiponectin inhibits palmitate-induced apoptosis by suppression of
      ROS generation via both the cAMP/PKA and AMPK pathways. Interaction between
      cAMP/PKA and AMPK pathways may be involved.

PMID- 20675306
TI  - Dynamic regulation of pituitary mRNAs for bone morphogenetic protein (BMP) 4, BMP
      receptors, and activin/inhibin subunits in the ewe during the estrous cycle and
      in cultured pituitary cells.
AB  - Recently, bone morphogenetic protein (BMP) 4 has been shown to inhibit FSH
      secretion in ewe. The detection of BMP4 mRNA and BMP receptors in the pituitary
      suggests that BMP4 can exert paracrine actions on FSH production. This work aimed
      at determining whether BMP4 and/or BMP receptor mRNA as well as activin/inhibin
      subunit mRNA fluctuates during the estrous cycle when FSHbeta mRNA and FSH
      release changed. The estrous cycles of ewes were synchronized with progestagen
      sponges. Ewes were killed in late follicular stage (n=5), before the secondary
      FSH surge (n=4), and in luteal phase (n=4). Using quantitative reverse
      transcription-PCR, we showed that the levels of mRNA for BMP4, BMP receptor, the
      inhibitor of differentiation 2 (Id2), a target gene of BMP4, and noggin did not
      change significantly across the estrous cycle. In contrast, the level of activin
      betaB mRNA and the percentage of immunoreactive cells for activin betaB-subunit
      were higher before the secondary surge of FSH compared to other groups. In ewe
      pituitary cell cultures, activin, GnRH, or estradiol-17beta (E(2)) did not
      significantly affect the levels of BMP4, BMP receptor, and Id2 mRNA. E(2), but
      not GnRH, increased the level of activin betaB mRNA. Moreover, the in vitro FSH
      release was not modified by noggin, a BMP antagonist. In contrast, SB431542, an
      inhibitor of activin pathway, inhibited FSH release. Collectively, our data
      showed that pituitary BMP4 would not play a crucial role in the regulation of FSH
      production during the estrous cycle, whereas local activin B would be a major
      stimulus of FSH synthesis necessary for the secondary FSH surge.

PMID- 20675308
TI  - The role of foot collateral vessels on ulcer healing and limb salvage after
      successful endovascular and surgical distal procedures according to an angiosome
      model.
AB  - OBJECTIVES: Analyze the influence of the collateral distal vessels on ischemic
      ulcer healing and limb salvage after successful distal procedures, according to
      an angiosome model. METHODS: Retrospective analysis of 76 ischemic ulcers
      revascularized by surgical (n = 41) and endovascular (n = 35) distal procedures.
      All interventions were primary procedures with single outflow vessel that
      remained patent during follow-up. Ulcers were classified according to an
      angiography angiosome study as ''direct revascularization'' ([DR] n = 45),
      ''indirect revascularization'' ([IR] n = 31), and IR ''through collaterals''
      ([IRc] n = 18). Healing rates and limb salvage were compared according to the
      type of revascularization. RESULTS: Ulcer healing rate at 12 months was higher in
      DR than in IR (92% vs 73%, P = .008) but similar to IRc (92% vs 85%). Limb
      salvage at 24 months was higher in DR than in IR (93% vs 72%, P = .02) but
      similar to IRc (93% vs 88%). CONCLUSION: Ulcer blood flow restoration through
      collateral vessels may give similar results to those obtained through its
      specific source artery.

PMID- 20675309
TI  - Acute infectious pseudoaneurysm of the descending thoracic aorta and review of
      infectious aortitis.
AB  - Thoracic aortic wall disruptions may occur secondary to trauma, surgical
      interventions, infection, or autoimmune or idiopathic inflammatory disorders.
      Such vessel wall disruption can lead to aortic dissections, aneurysm development,
      or more commonly, pseudoaneurysm (PSA) formation. Although aortic wall infections
      as an antecedent to mycotic aneurysms have been recognized since the 17th
      century, there has been a temporal evolution in the development of this disease.
      Prior to the antibiotic era they were commonly associated with endocarditis or
      syphilis. More recently, however, they are associated with infection of a damaged
      atherosclerotic area of the aorta and secondary hematogenous or contiguous
      seeding. We report the first case of the rapid development of a pseudoaneurysm in
      the descending thoracic aorta attributable to an infection of a contiguous
      esophageal duplication cyst by a diagnostic esophageal ultrasound (EUS) fine
      needle aspiration. A literature review of mycotic thoracic aortic aneurysms and
      pseudoaneurysms is also presented.

PMID- 20675310
TI  - Conversion of tunneled hemodialysis catheter into HeRO device can provide
      immediate access for hemodialysis.
AB  - Patients with central venous occlusion who are ''tunneled catheter dependent''
      are a challenge for hemodialysis access. A relatively new option for them is the
      hemodialysis reliable outflow (HeRO) device that can be totally implanted
      subcutaneously. However, patients still require a tunneled hemodialysis catheter
      that is used until the HeRO device is mature, 4 to 6 weeks later. Here, we
      describe a conversion of an existing tunneled hemodialysis catheter into a HeRO
      device, which was combined with a ''self-sealing'' Flixene graft. This allowed
      almost immediate use of the HeRO device without the need for placement of a
      catheter.

PMID- 20675311
TI  - Delayed release of an Amplatzer vascular plug in the treatment of a hypogastric
      artery aneurysm.

PMID- 20675312
TI  - Antibiotics for preventing progression of abdominal aortic aneurysms: a meta
      analysis of randomized trials.

PMID- 20675313
TI  - A novel treatment approach to a type II endoleak at endograft implantation using
      components of an endosensor monitoring device.
AB  - PURPOSE: There continues to be debate regarding optimal management of type II
      endoleaks following endovascular abdominal aortic aneurysm repair. CASE REPORT:
      We present an intraoperative treatment approach to type II endoleaks using
      components of the EndoSure Intrasac Pressure Monitor System. Our technique can
      easily be reproduced with commercially available guidewires and catheters. We
      also present a literature review that identifies type II endoleak characteristics
      associated with a high rate of persistence (high-risk endoleaks) and could
      benefit from early treatment. CONCLUSIONS: If a high-risk type II endoleak is
      identified intraoperatively, those patients may benefit from our model of an
      early intervention strategy. Early definitive treatment of the endoleaks could
      result in lower morbidity and reintervention rates.

PMID- 20675314
TI  - Long-term functional results for the surgical management of neurogenic thoracic
      outlet syndrome.
AB  - OBJECTIVE: To document long-term functional outcomes in patients treated for
      neurogenic thoracic outlet syndrome (NTOS). METHODS: Records of all patients
      undergoing treatment for NTOS at our center were reviewed. Patient demographics
      and co-morbidities were recorded. End-points included symptomatic relief, peri
      operative adjunctive procedures, functional outcome and employment continuity.
      RESULTS: From 1988-2008, 26 patients were operated upon for NTOS. Hallmarks of
      the diagnosis in operated patients included symptom duration less than 1 year and
      a positive Roos test. Patients receiving disability and those with cervical spine
      pathology or carpal tunnel syndrome were not considered for surgery. Mean patient
      age was 39.2 years (range 14-60 years) with a mean follow-up of 104.4 months.
      Eleven patients (42.3%) engaged in pre-operative physical therapy programs. 7 of
      9 patients (26.9%) received adjunctive peri-procedural scalene block with
      temporary symptom relief. All patients underwent thoracic outlet decompression by
      either 1st rib resection [18 total: 8 (44%) transaxillary and 10 (66%)
      supraclavicular)], cervical rib resection [6 (26.1%)] and/or scalenectomy [12
      (46.2%)]. Of the 22 patients available for follow-up, six patients (27.3%) have
      required continued post-operative narcotic analgesics. Sixteen patients (72.7%)
      returned to work and reported being at an equivalent or better functional outcome
      than their pre-operative status. CONCLUSIONS: Durable long-term functional
      outcomes can be achieved predicated on a highly selective approach to the
      surgical management of patients with NTOS. A majority of operated patients will
      not require adjunctive procedures or chronic narcotic utilization. Patients who
      undergo surgery can expect to return to work with little or no functional
      impairment.

PMID- 20675315
TI  - Early mortality following endovascular versus open repair of ruptured abdominal
      aortic aneurysms.
AB  - PURPOSE: To determine whether endovascular repair (EVAR) offers a survival
      advantage over open repair (OAR) with ruptured abdominal aortic aneurysms (RAAA).
      METHODS: Retrospective analysis of RAAA patients treated between 2003 and 2008.
      Univariate and multivariate analyses were performed. RESULTS: 167 patients
      presented with RAAA (OAR = 135, 80.8%, EVAR = 32, 19.2%). On univariate analysis,
      EVAR was associated with a decreased mortality relative to OAR, (15.6% vs 43.7%,
      P = .004). Patients who survived were younger (P < .0005), had a higher blood
      pressure (P < .0005), level of consciousness (P < .0005), and hemoglobin (P =
      .018), and a lower urea (P = .005) and international normalized ratio (INR; P =
      .001). On multivariate analysis, type of repair remained an independent predictor
      of 30-day mortality (OR: 0.121; 95% CI: 0.021-0.682, P = .017). CONCLUSION:
      Controlling for preoperative factors, EVAR is an independent predictor of lower
      30 day mortality relative to open repair after RAAA. This supports the wider use
      of endovascular repair in all patients with RAAA.

PMID- 20675316
TI  - Open repair and endovascular covered stent placement in the management of
      bilateral axillary artery aneurysms.
AB  - A 72-year-old male with chronic obstructive pulmonary disease and hyperlipidemia
      presented with acute right upper limb ischemia. Arterial occlusion was found to
      be secondary to a thrombosed axillary artery aneurysm. An open repair was
      performed with a polytetrafluoroethylene (PTFE) graft. On further workup, the
      patient was found to have an asymptomatic axillary artery aneurysm on the left
      hand side. Endovascular repair with a covered stent was chosen to treat this
      aneurysm.

PMID- 20675317
TI  - The effects of acarbose treatment on intimal hyperplasia in a rat carotid
      endarterectomy model of diet-induced insulin resistance.
AB  - BACKGROUND: Increased carotid restenosis due to revascularization therapy is
      associated with insulin resistance. We hypothesize that glucose control using
      acarbose may attenuate intimal hyperplasia in rat carotid endarterectomy model of
      diet-induced insulin resistance. METHODS: Rats were fed low-fat complex
      carbohydrate (control) or high-fat sucrose (insulin resistance) for 4 months.
      Three days preoperatively, some high-fat-sucrose rats were on acarbose, remainder
      of the rats received placebo. Rat carotids were assessed with duplex pre-and
      postoperatively. Acarbose and placebo continued for 2 weeks. Glucose, insulin,
      blood flow velocities and intimal hyperplasia were determined. RESULTS: High-fat
      sucrose plus acarbose attenuated intimal hyperplasia. Post-drug high-fat sucrose
      glucose decreased. Blood flow velocities postoperatively elevated above baseline.
      High-fat sucrose increased blood flow velocities postoperatively, which was
      attenuated with acarbose. CONCLUSION: Glucose control by acarbose in rat carotid
      endarterectomy model of diet-induced insulin resistance resulted in attenuation
      of intimal hyperplasia.

PMID- 20675318
TI  - Diagnostic accuracy of contrast-enhanced magnetic resonance angiography and
      duplex ultrasound in patients with peripheral vascular disease.
AB  - INTRODUCTION: Noninvasive techniques such as duplex ultrasound (DU) and contrast
      enhanced magnetic resonance angiography (CE-MRA) are valid alternatives in the
      preoperative evaluation of such patients. Our aim is to assess the diagnostic
      accuracy of CE-MRA and DU in patients with peripheral arterial disease (PAD).
      METHODS: Forty consecutive patients underwent DU, hybrid CE-MRA, and digital
      subtraction angiography (DSA). Magnetic resonance angiography and DSA images were
      evaluated independently and in a blinded fashion. Every segment was graded as
      normal, stenosed less than 50%, stenosed more than 50%, or occluded. RESULTS:
      There were 1720 segments for analysis. Duplex ultrasound depicting stenosis >50%
      demonstrated a sensitivity (S) 81.4%, specificity (E) 99%, positive predictive
      value (PPV) 96.2%, and negative predictive value (NPV) 94.8%. Occlusions showed S
      90%, E 97%, PPV 98.1%, and NPV 88.4%. Magnetic resonance angiography depicting
      stenosis >50% demonstrated a S 91%, E 99%, PPV 96.7%, and NPV 97.6%. Occlusions
      showed S 95.4%, E 98%, PPV 98.4%, and NPV 94.7%. CONCLUSION: Combined CE-MRA and
      DU is the first diagnostic approach in the preoperative assessment of PAD,
      leading to the use of DSA for selected cases.

PMID- 20675319
TI  - Lymphangiography in the diagnosis, localization, and treatment of a
      lymphaticopelvic fistula causing chyluria: a case report.
AB  - We present a 25-year-old man with chyluria resulting from a posttraumatic,
      postinflammatory lymphaticopelvic fistula. This aberrant connection between the
      lymphatic system and the urinary tract is rarely seen in the United States and
      can be difficult to diagnose. In this particular case, lymphangiography and
      postprocedure computed tomography (CT) imaging were used to diagnose and localize
      a fistula involving the right renal pedicle lymphatics and right urinary
      collecting system. This fistula ultimately resolved after the procedure and did
      not require sclerotherapy or surgical intervention. Lymphangiography is now
      rarely performed at most centers due to advancements in alternative diagnostic
      imaging modalities. However, this procedure remains a useful tool for the
      investigation and treatment of chyluria and other chyle leaks.

PMID- 20675320
TI  - Arterial pressure gradient of upper extremity arteriovenous access steal
      syndrome: treatment implications.
AB  - PURPOSE: Treatment options after arteriovenous fistula (AVF) associated steal
      include ligation, banding, and distal revascularization-interval ligation (DRIL).
      The purpose of this study was to evaluate the arterial pressure gradients in
      upper extremity steal syndrome. METHODS: Preoperative arteriography and
      sequential intra-arterial pressure readings were performed on consecutive AVF
      patients with hand ischemia. Analysis of variance (ANOVA) with repeated measures
      analyzed intersubject comparisons, and post hoc analysis identified anatomic
      locations with highest inflow pressures. RESULTS: Nine patients presented with
      ischemic hand symptoms after AVF. Pullback arterial pressure measurements
      revealed gradual increases in systolic and mean pressures as the catheter
      position was moved proximally from the AVF anastomosis. Post hoc analysis after
      ANOVA revealed higher axillary artery systolic pressure compared to proximal
      brachial artery (153 vs 116.8, P = .007). CONCLUSION: AVF-related steal syndrome
      decreases arterial inflow pressure of the affected extremity more proximally than
      previously thought. When performing a DRIL procedure, consideration should be
      given to placing the anastomosis as proximally as possible.

PMID- 20675321
TI  - Brachial artery aneurysm following open repair of posttraumatic false aneurysm
      and arteriovenous fistula.
AB  - True brachial artery aneurysms remain extremely rare and are most commonly
      related to repetitive blunt trauma. Although operative repair of false aneurysms
      is well established, management of true aneurysms is varied due to their rarity.
      We present a true brachial artery aneurysm, in a 55-year old male, which occurred
      some 22-years following the repair of a posttraumatic false aneurysm. Following
      arterial duplex and computerised tomography, aneurysectomy with reversed
      interposition vein graft was performed.

PMID- 20675322
TI  - Percutaneous drainage of aortic aneurysm sac abscesses following endovascular
      aneurysm repair.
AB  - PURPOSE: To report preliminary experiences with the treatment of aortic aneurysm
      sac abscesses following prior endovascular aortic aneurysm repair (EVAR) using
      computerized tomography (CT)-guided percutaneous drainage. CASE REPORTS: Three
      patients aged 73 to 78 years with aortic aneurysm sac infections following prior
      EVAR, 2 of which were associated with aortoduodenal fistula, underwent CT-guided
      percutaneous drainage and catheter placement. One patient had complete resolution
      of the aortic aneurysm sac abscess following percutaneous drainage; 1 patient was
      stabilized to eventual extraanatomic bypass, graft explantation, and fistula
      repair; and 1 patient was temporized to debridement and fistula repair with
      endograft preservation. CONCLUSION: CT-guided percutaneous drainage may be a
      helpful therapy in selected patients for the treatment of aortic aneurysm sac
      infections following EVAR.

PMID- 20675323
TI  - Endovascular management of mycotic aortic aneurysms.
AB  - PURPOSE: We report a single-center experience with the endovascular management of
      mycotic aortic aneurysms. CASE REPORTS: Four cases of mycotic aortic aneurysms
      are described; all treated with endovascular stent graft with variable
      configurations. All patients underwent successful placement of stent grafts for
      their aneurysms. No 30-day perioperative mortality was observed. One patient died
      during the follow-up period from a cause unrelated to the aneurysm. CONCLUSION:
      Repair of mycotic aneurysms can be accomplished with endovascular repair. This
      may be a valid alternative to open repair particularly in patients who are not
      candidates for conventional open repair.

PMID- 20675324
TI  - Subintimal angioplasty for advanced lower extremity ischemia due to TASC II C and
      D lesions of the superficial femoral artery.
AB  - OBJECTIVE: Subintimal angioplasty (SA) has evolved into a viable
      revascularization procedure for complex lower extremity lesions. Although patency
      rates are lower than those for autogenous bypass, limb salvage rates are
      comparable. This study reviewed the 8-year experience of SA in a single center.
      METHODS: Records of patients undergoing SA were reviewed. Clinical presentation
      and noninvasive exams were used to classify patients. Lesions were categorized by
      TransAtlantic InterSociety Consensus (TASC) II guidelines. Outcomes included
      technical success, patency, amputation-free survival, and limb salvage. RESULTS:
      120 patients with TASC II C/D lesions underwent SA. Technical success was 91%.
      Primary patency at 6 and 12 months was 90% and 73%. Secondary patency at 6 and 12
      months was 94% and 85%. One-year amputation-free survival was 90%. One-year limb
      salvage was 98%. CONCLUSIONS: SA for TASC C/D lesions is a safe procedure and may
      be considered an alternative to bypass, especially in high-risk patients.

PMID- 20675325
TI  - Endovascular retrieval of inferior vena cava filter penetrating into aorta: an
      unusual presentation of abdominal pain.
AB  - Inferior vena cava filters are commonly used in patients with contraindications
      to or failures of treatment with anticoagulation. However, these are not without
      complications. Serious complications include penetration of the filter struts
      into adjacent structures, including the aorta. The design of permanent filters
      makes retrieval in the instance of life-threatening complication complex, often
      requiring extensive surgical exploration. Retrievable filters may be more easily
      removed via endovascular methods, reducing the morbidity of surgical approaches.

PMID- 20675326
TI  - Infrarenal origin of the superior mesenteric artery: implications in endovascular
      repair of abdominal aortic aneurysm.
AB  - Endovascular aneurysm repair (EVAR) has become the preferred modality for the
      treatment of infrarenal abdominal aortic aneurysms (AAAs). A variety of anatomic
      factors must be considered when planning EVAR, including the relationship of the
      visceral arteries to the aneurysmal segment of the aorta. This report describes 2
      patients with infrarenal AAA in whom the superior mesenteric artery was the most
      caudal visceral vessel, originating inferior to the renal arteries.

PMID- 20675327
TI  - Damage control in the management of ruptured abdominal aortic aneurysm:
      preliminary results.
AB  - BACKGROUND: This study compared damage control measures (DCM), including
      operative techniques (DCO) and resuscitative measures (DCR), with standard
      treatment (ST) for ruptured abdominal aortic aneurysm (rAAA). METHODS: Historical
      cohort study methodology was used to evaluate outcomes for rAAA repairs related
      to DCM or ST over a 74-month period at a level I trauma center. RESULTS: Of 28
      repairs, 13 (46.4%) were DCM. Compared to ST patients, DCM patients had a lower
      mean preoperative BP (64.6 vs. 83.2 mm Hg, P = .03) and greater intraoperative
      blood loss (4.6 vs. 2.1 liters, P = .033). Patients who had both DCR and DCO (DCO
      & DCR) received more plasma (6.8 vs 2.6 units, P = .039) and less crystalloid
      (2.8 vs 10.5 liters, P = .005) than those receiving DCO only. A modest decrease
      in mortality was seen in the DCO & DCR group compared to DCO only. No DCO-related
      graft infections were observed. CONCLUSION: DCR use may prove beneficial in the
      management of rAAA.

PMID- 20675328
TI  - Changing from conventional to eversion endarterectomy in carotid artery disease-
      a safe transition process in the short and long term.
AB  - OBJECTIVES: To evaluate the transition process from conventional carotid
      endarterectomy (cCEA) to eversion carotid endarterectomy (eCEA). METHODS:
      Patients operated with carotid endarterectomy (CEA; 164 patients, 171 CEA) in
      2002-2003 were retrospectively included. RESULTS: In 2002, cCEA was applied in 64
      (80%) and eCEA in 16 (20%) patients. There was an inversion on the preponderant
      surgical technique in 2003 (cCEA in 34 patients [37%] and eCEA in 57 patients
      [63%]). Perioperative stroke or death occurred in 3 patients (3.8%) in 2002 and 5
      (5.5%) in 2003 (P = .78). Perioperative myocardial infarction occurred in 2
      patients (2.5%) in 2002 and 2 in 2003 (2.2%, P = 1.00). Median follow-up was 83
      (79-86) and 70 (67-74) months for the 2002 and 2003 cohorts, respectively, and
      there were no differences in survival or ipsilateral stroke between the groups.
      CONCLUSIONS: The transition from cCEA to eCEA is possible without significant
      changes in morbidity and mortality perioperatively and during follow-up.

PMID- 20675329
TI  - Endovenous ablation plus microphlebectomy/sclerotherapy for the treatment of
      varicose veins: single or two-stage procedure?
AB  - OBJECTIVE: The purpose of this study was to establish how often after the
      performance of endovenous ablation (EA), a second stage is required. METHODS:
      Eighty-six consecutive lower extremities in 76 patients treated with laser EA
      were the cohort of this study. The clinical result after EA at 1 month was
      classified as excellent (no varicosities), good (major reduction in size), and
      poor (no change). Need for further intervention (sclerotherapy or
      microphlebectomy) was determined at the 1-month follow-up. RESULTS: Complete
      resolution of varicosities after EA was found in 36 extremities (41.8%),
      reduction in size in 48 extremities (55.8%), and no change in 2 extremities
      (2.3%). Of the 86 extremities studied, 36 (41.8%) were considered in need of a
      second stage procedure. CONCLUSION: After EA, 58.2% of extremities did not
      require further treatment. These results add further justification to the
      performance of EA alone as a first stage.

PMID- 20675330
TI  - Carotid stenting and transcranial Doppler monitoring: indications for carotid
      stenosis treatment.
AB  - BACKGROUND: Recently, angioplasty and stenting of carotid arteries (CAS) have
      taken the place of surgery. The aim of our study is to assess the role of
      transcranial Doppler (TCD) monitoring during CAS to address the embolic
      complications during the stages of the procedure, with or without embolic
      cerebral protection devices. METHODS: A total of 152 patients were submitted to
      carotid stenting. All patients were submitted to carotid arteries Duplex
      scanning. RESULTS: Neurological complications are related to TCD detection of
      corpuscolate signals in rapid succession. Even if no reduction of the overall
      incidence rate of microembolic signals (MES) was observed, a decrease in the
      number of corpuscolate emboli were recorded when a cerebral protection was
      working. CONCLUSIONS: According to our study, even in selected patients on the
      basis of preoperative diagnostic criteria, CAS is burdened by a nonnegligible
      risk of subclinical embolic ischemic events detected at TCD and confirmed by
      diffusion-weighted magnetic resonance imaging (DW-MRI).

PMID- 20675331
TI  - A case of limb ischemia secondary to paradoxical embolism.
AB  - Paradoxical embolism is rarely considered a cause for acute limb ischemia.
      Although patent foramen ovales (PFOs) are often seen in young patients with
      stroke, clinicians may not consider evaluation for PFOs in young patients with
      acute peripheral ischemia. We present a 47-year-old patient presenting with lower
      extremity ischemia secondary to paradoxical embolism. This case highlights the
      importance of evaluating for paradoxical embolism in otherwise-unexplained cases
      of acute limb ischemia.

PMID- 20675332
TI  - Centralization harnessing volume-outcome relationships in vascular surgery and
      aortic aneurysm care should not focus solely on threshold operative caseload.
AB  - There has been great interest in the setting of threshold operative volumes for
      safety to guide centralisation of vascular surgical services by healthcare
      commissioners. This editorial examines the evidence for designing services around
      a numeric safety threshold in the relationship between volume and outcome in
      vascular surgery. Thresholds should be aimed at the best outcomes and equity of
      care. Equity means access to the most up-to-date technology and all the relevant
      support services for elective and emergency cases. The relationship of volume and
      outcome with quality is complex, and demands a shift in focus to infrastructural
      and procedural improvements that drive high-quality services rather than the
      concentration of planning exclusively around an operative volume threshold.

PMID- 20675333
TI  - The patients' perspective of carotid endarterectomy.
AB  - INTRODUCTION: No studies as yet have directly evaluated the patients' perspective
      of carotid endarterectomy (CEA). Here, we determine patient satisfaction,
      understanding, and perception of CEA. METHODS: Consecutive patients were
      identified from a prospectively maintained carotid database. A validated 10-point
      telephone questionnaire was conducted. Questions related to preoperative
      symptoms, experience of procedure, future interventions, and overall patient
      satisfaction. RESULTS: Of the 192 patients included, 136 completed the
      questionnaire (71% response rate). Ninety-two percent were satisfied with the
      explanation received, however, only 48% understood that CEA aimed to prevent
      future stroke. Eighty-five percent of patients received local anesthesia (LA)
      CEA, with 16% reporting severe or unbearable pain. Most patients (83%) would
      repeat CEA if necessary and 67% stated a future preference for LA CEA. The
      majority of patients (96%) were satisfied with their treatment overall.
      CONCLUSIONS: Most patients were satisfied with CEA. Greater emphasis could be
      placed on improving preoperative information-giving and intraoperative analgesia.

PMID- 20675334
TI  - Diabetic limb salvage: too much of a good thing?
AB  - Diabetic foot complications exact a significant toll on patients specifically and
      the health care system in general. Most data suggest that limb preservation
      generally results in a higher quality (and quantity) of life for the patient and
      lower overall direct and indirect costs. However, when focusing on a specific
      patient, significant questions remain. The most significant being: how much
      effort is too much? The purpose of this manuscript is to present a case that
      explores this issue.

PMID- 20675335
TI  - Endovascular embolization of iatrogenic lumbar artery pseudoaneurysm following
      extreme lateral interbody fusion (XLIF).
AB  - Iatrogenic lumbar artery pseudoaneurysm is a very rare complication of spinal
      surgery. To the best of our knowledge, this is the first report of a lumbar
      artery pseudoaneurysm after extreme lateral interbody fusion (XLIF). The lesion
      was diagnosed by catheter spinal angiography and was effectively treated with
      embolization.

PMID- 20675336
TI  - Vascular surgical antibiotic prophylaxis study (VSAPS).
AB  - This prospective, randomized study was performed at a single institution. Low
      risk patients undergoing elective vascular procedures were enrolled (August 2007
      to June 2009). Participants were randomized into 3 separate arms. They received
      cefazolin, cefazolin + vancomycin, or cefazolin + daptomycin prior to surgery. In
      total, 169 patients were included in the analysis. Mean age was 64 (range, 26
      85), and the patients' comorbidities were similar across all groups. Only
      Szilagyi II and III infections were analyzed. Any infection/methicillin-resistant
      Staphylococcus aureus (MRSA) infections was seen in 8 (12.9%)/2 (3.23%) in the
      cefazolin group, 7 (12.5%)/4 (7.14%) in the cefazolin + vancomycin group, and 2
      (3.92%)/(0%) in the cefazolin + daptomycin group. In this study, population of
      low-risk patients undergoing elective vascular procedures, there was a trend
      toward fewer infectious complications in the cefazolin + daptomycin group. Adding
      anti-MRSA agents to the current standard prophylaxis regimen does not appear to
      reduce the incidence of MRSA infection in low-risk patients.

PMID- 20675337
TI  - Diagnosis and surgical management of free-floating thrombus within the carotid
      artery.
AB  - OBJECTIVE: Free-floating thrombus (FFT) of the carotid artery is a rare condition
      of currently unknown etiology. Less than 150 cases have been described in the
      published world literature to date. DESIGN AND SETTING: We present 6 consecutive
      cases of carotid FFT, identified prospectively from 5000 carotid duplex scans
      over a 34-month period in a single tertiary center for vascular surgery. RESULTS:
      All 6 cases involved the left carotid bifurcation in neurologically symptomatic
      individuals. In 5 of the 6 cases, FFT occurred in the absence of a significantly
      stenosing atheromatous plaque and was not associated with an elevation in
      velocity on duplex. The patients were all treated with surgical
      thromboendarterectomy, with good result. CONCLUSIONS: Duplex imaging can
      underestimate the degree of stenosis. Free-floating thrombus presents a challenge
      in diagnosis due to its rapidly evolving nature. The management of FFT by acute
      thromboendarterectomy appears to be safe and effective in limiting further focal
      neurological sequelae.

PMID- 20675338
TI  - The coronary technique for complex carotid artery stenting in the setting of
      complex aortic arch anatomy.
AB  - Carotid artery stenting (CAS) remains a viable option for treating carotid artery
      lesions in high surgical risk patients. We retrospectively reviewed our
      experience in performing CAS in patients with complex aortic arch anatomy. The
      ''coronary technique'' uses an AL1 guiding catheter to engage the origin of the
      common carotid artery permitting delivery of protection device and stent. In
      total, 12 patients had complex arch anatomy which precluded access using the
      standard technique as determined on preoperative imaging. A total of 8 patients
      with such anatomy underwent femoral artery catheterization with placement of an
      Amplatz AL1 guide catheter into the common carotid artery. All were able to be
      successfully treated, with no dissection, neurovascular deficit, or other major
      complication. Based on this case series, we describe the coronary technique as a
      safe and viable method for CAS in the setting of complex anatomy which might
      otherwise preclude CAS.

PMID- 20675339
TI  - Pseudoaneurysm of high origin ulnar artery after penetrating trauma.
AB  - High origin ulnar artery from the brachial artery is rare and lies superficially
      in the forearm. Its reported frequency ranges from 0.17% to 2%. Pseudoaneurysms
      of peripheral arteries are very rare, and mostly these are the result of
      penetrating injuries. Here, we report a case pseudoaneurysm of high origin ulnar
      artery from the brachial artery and its surgical approach method.

PMID- 20675340
TI  - Subclavian artery access for transcatheter aortic valve implantation and
      cardiopulmonary support.

PMID- 20675341
TI  - An improved anion-exchange high-performance liquid chromatography method for
      measuring oxidized form of LDLs in human plasma.
AB  - BACKGROUND: Circulating oxidized low-density lipoproteins (LDLs) (ox-LDLs) could
      be a sensitive marker to predict future cardiovascular events. However, a method
      to evaluate oxidized forms of LDLs systemically in human plasma is not yet
      established. In this study, we developed a novel and convenient high-performance
      liquid chromatography (HPLC) method for measuring ox-LDL levels in humans.
      METHODS: Human plasma lipoproteins were separated by a modified HPLC method using
      a diethylaminoethyl-type anion-exchange gel column with stepwise elution. Ox-LDLs
      were detected by postcolumn reaction with a reagent containing cholesterol
      esterase and cholesterol oxidase. Particle size of each LDL fraction separated by
      HPLC was determined in 61 healthy subjects. RESULTS: Our HPLC method separated
      LDLs into three fractions, which were designated as LDL-1, LDL-2 and LDL-3, on
      the basis of their negative charges, with LDL-3 the most strongly retained
      fraction migrating fastest in the anodic direction, a property that reflects the
      net negative charge of the molecule. Western blot analysis revealed that
      apolipoprotein B100 in LDL-3 fraction was the most fragmented and oxidatively
      modified. When LDLs were oxidized in vitro by Cu2+ or 2,2-azo-bis (2
      aminopropane)-2HCl or modified by various aldehydes, all of the LDL fractions
      migrated at the position of LDL-3. Further, among three fractions, particle size
      was smallest in LDL-3 fraction. CONCLUSION: Here, we developed a convenient HPLC
      method and identified LDL-3 as oxidized LDL fractions, although ox-LDLs were
      present in LDL-2 fraction, albeit lesser concentrations than in LDL-3
      subfraction. Measuring ox-LDL levels in human plasma by this method may be useful
      to evaluate atherosclerotic disorders.

PMID- 20675342
TI  - On the efficiency and effectiveness of added-on serum magnesium in patients with
      hypokalaemia and hypocalcaemia.

PMID- 20675343
TI  - The miR-217 microRNA functions as a potential tumor suppressor in pancreatic
      ductal adenocarcinoma by targeting KRAS.
AB  - Aberrantly expressed microRNA (miRNA) is frequently associated with a variety of
      cancers, including pancreatic ductal adenocarcinoma (PDAC). In this study, we
      investigated the expression and possible role of miR-217 in PDAC. Data obtained
      by locked nucleic acid in situ hybridization and real-time quantitative
      polymerase chain reaction showed that miR-217 was downregulated in 76.2% (16/21)
      of PDAC tissues and in all tested PDAC cell lines when compared with the
      corresponding normal pancreatic tissue. Overexpression of miR-217 in PDAC cells
      inhibited tumor cell growth and anchorage-independent colony formation and miR
      217 decreased tumor cell growth in nude mouse xenografts in vivo. Using in silico
      predictions, KRAS was defined as a potential direct target of miR-217. Data from
      the dual-luciferase reporter gene assay showed that KRAS was a direct target of
      miR-217. Upregulation of miR-217 could decrease KRAS protein levels and reduce
      the constitutive phosphorylation of downstream AKT. Downregulation of miR-217
      expression in PDAC cells could increase cell anchorage-independent colony
      formation and KRAS protein levels. Furthermore, miR-217 expression was observed
      to be negatively correlated with KRAS protein expression in PDAC cell lines. We
      conclude that the frequently downregulated miR-217 can regulate KRAS and function
      as a tumor suppressor in PDAC. Therefore, miR-217 may serve as a useful
      therapeutic agent for miRNA-based PDAC therapy.

PMID- 20675344
TI  - Changing access to emergency care for patients undergoing outpatient procedures
      at ambulatory surgery centers: evidence from Florida.
AB  - The growth of ambulatory surgery centers (ASCs) as a setting for care in the
      United States raises unique safety concerns. In contrast to hospital-based
      outpatient departments (HOPDs), ASCs offer care at varying distances from
      hospital services potentially required to treat complications. To describe
      changes over time in the accessibility of hospital services for procedural
      outpatients, this study examined 4.3 million discharges for seven outpatient
      procedures frequently performed at ASCs and HOPDs. Between 2005 and 2007, the
      mean patient-to-emergency department (ED) distance increased by 12.4%. This
      change, which resulted from both an increase in the share of procedures performed
      at ASCs and an increase in the distance between ASCs and EDs, occurred
      predominantly within procedures that carried an elevated odds of hospital
      admission relative to the lowest risk procedures. Further research defining the
      risks associated with these changes in access to emergency care is needed to
      inform future ASC policy development and regulation.

PMID- 20675345
TI  - Improving communication between patients and providers using health information
      technology and other quality improvement strategies: focus on Asian Americans.
AB  - Disparities in provider-patient communication have been shown to exist among
      Asian Americans, especially those who are low-income and have limited English
      proficiency. These disparities have resulted in unmet health care needs and poor
      quality care. To identify strategies for improving provider-patient communication
      in this population, we conducted a systematic review of the literature and in
      depth interviews with key informants. Little published literature on
      interventions focused on Asian Americans was found. Most interventions were
      conducted among White populations and occurred in the waiting room before
      patients' visits with their providers. Interventions ranged from a leaflet
      encouraging patients to ask more questions, to more intensive face-to-face
      coaching before office visits. Health information technology (health IT) has not
      been widely used to improve communication, especially among patients with limited
      English proficiency. More research is needed using new health IT strategies to
      improve care for Asian Americans and other vulnerable populations.

PMID- 20675346
TI  - Improving communication between patients and providers using health information
      technology and other quality improvement strategies: focus on low-income
      children.
AB  - Effective communication between providers and patients has been linked to
      improved outcomes. Previous reviews of quality improvement strategies, including
      health information technology (health IT), have not focused on the needs of low
      income children. The authors conducted a systematic review of the literature on
      studies of communication surrounding the care of low-income children, with an
      emphasis on interventions and health IT.The search yielded six studies that
      focused on low-income children; three of the studies used health IT. Key
      informant interviews provided insight to the current use of health IT for
      provider-patient communication in geographically diverse, underresourced
      settings.The authors identify gaps between existing literature and clinical
      practice. Future research should focus on the specific impact of health IT in
      pediatric medicine, particularly in underresourced and safety net settings. These
      efforts should focus on the use of technological innovations to improve care for
      low-income children and their families.

PMID- 20675347
TI  - Impact of Medicaid/ SCHIP disenrollment on health care utilization and
      expenditures among children: a longitudinal analysis.
AB  - This study examines the impact of disenrolling from Medicaid/State Children's
      Health Insurance Programs (SCHIP) on health care utilization and expenditures
      among children using the 1996-2005 Medical Expenditure Panel Survey data. Changes
      in expenditures and utilization upon Medicaid/SCHIP disenrollment were examined
      for two disenrollment groups, children who became uninsured and those who
      transitioned to private insurance; relative to a control group, those
      continuously enrolled in Medicaid/SCHIP during the study period. In multivariate
      analysis, a modified two-part model and difference-in-difference analytic
      approach were used. The dependent variables were changes in total expenditures
      and changes in utilization (i.e., well-child visits, physician visits, emergency
      room visits, hospitalizations, and prescription drug use) from pre- to post
      disenrollment round. This study found that losing Medicaid/SCHIP coverage is
      associated with decreased preventive care utilization among children, regardless
      of the insurance status post-disenrollment. In addition, children who become
      uninsured following Medicaid/SCHIP disenrollment may also experience reductions
      in physician visits and prescription drug use.

PMID- 20675348
TI  - Health information technology and quality of health care: strategies for reducing
      disparities in underresourced settings.
AB  - Health information technology (health IT) has potential for facilitating quality
      improvement and reducing quality disparities found in underresourced settings
      (URSs). With this systematic literature review, complemented by key informant
      interviews, the authors sought to identify evidence regarding health IT and
      quality outcomes in URSs. The review included 105 peer-reviewed studies (2004
      2009) in all settings. Only 15 studies included URSs, and 8 focused on URSs.
      Based on literature across settings, most evidence was available for quality
      impact of order entry, clinical decision support systems, and computerized
      reminders. Study designs were predominantly quasi-experimental (37%) or
      descriptive (35%); 90% of the studies focused on the microsystem level of quality
      improvement, indicating a need for expanding research into patient experience and
      organizational and environmental levels. Key informants highlighted
      organizational partnerships and health IT champions and emphasized that for
      health IT to have an impact on quality, there must be an organizational culture
      of quality improvement.

PMID- 20675349
TI  - Characterizing declines in pediatric antidepressant use after new risk
      disclosures.
AB  - Steep declines in pediatric antidepressant use were documented following the 2004
      release of new safety information associating antidepressants with a risk of
      suicidality. The authors examine whether declines in pediatric antidepressant use
      were steeper among individuals with certain clinical or family characteristics.
      The authors find that declines in antidepressant use were associated with new (as
      compared with ongoing) treatment episodes. Although rates of antidepressant use
      were higher among children of college-educated parents prior to risk disclosures,
      these children were more likely to forgo antidepressant medication than children
      of less educated parents after risk disclosures. The authors find that both
      children with and without psychiatric impairment experienced declines in
      antidepressant medication use following the risk warnings, although the decline
      occurred more quickly in the latter group. The authors' findings highlight the
      need for additional data to assess the effects of risk disclosures on treatment
      patterns and health outcomes.

PMID- 20675350
TI  - The use of quality improvement and health information technology approaches to
      improve diabetes outcomes in African American and Hispanic patients.
AB  - Differences in rates of diabetes-related lower extremity amputations represent
      one of the largest and most persistent health disparities found for African
      Americans and Hispanics compared with Whites in the United States. Since many
      minority patients receive care in underresourced settings, quality improvement
      (QI) initiatives in these settings may offer a targeted approach to improve
      diabetes outcomes in these patient populations. Health information technology
      (health IT) is widely viewed as an essential component of health care QI and may
      be useful in decreasing diabetes disparities in underresourced settings. This
      article reviews the effectiveness of health care interventions using health IT to
      improve diabetes process of care and intermediate diabetes outcomes in African
      American and Hispanic patients. Health IT interventions have addressed patient,
      provider, and system challenges in the provision of diabetes care but require
      further testing in minority patient populations to evaluate their effectiveness
      in improving diabetes outcomes and reducing diabetes-related complications.

PMID- 20675351
TI  - Innovative strategies to reduce disparities in the quality of prenatal care in
      underresourced settings.
AB  - This study examined what innovative strategies, including the use of health
      information technology (health IT), have been or can be used to reduce
      disparities in prenatal care quality in underresourced settings. Based on
      literature review and key informant interviews, the authors identified 17
      strategies that have been or can be used to (a) increase access to timely
      prenatal care, (b) improve the content of prenatal care, and (c) enhance the
      organization and delivery of prenatal care. Health IT can be used to (a) increase
      consumer awareness about the importance of preconception and early prenatal care,
      facilitate spatial mapping of access gaps, and improve continuity of patient
      records; (b) support collaborative quality improvement, facilitate performance
      measurement, enhance health promotion, assist with care coordination, reduce
      clinical errors, improve delivery of preventive health services, provide decision
      support, and encourage completeness of documentation; and (c) support data
      integration and engineer collaborative innovation.

PMID- 20675352
TI  - Synonyms in health services research methodology.
AB  - There are often multiple discipline-specific terms for a given statistical
      concept, which can sow confusion in multidisciplinary teams or study sections if
      researchers are not aware of the synonyms from other disciplines. This article
      incorporates synonyms and a uniform definition of terminology related to study
      designs, elements of an equation, and types of bias. Greater multidisciplinary
      collaboration and exploration of new methods can be facilitated by this methods
      thesaurus.

PMID- 20675353
TI  - Use of qualitative methods in published health services and management research:
      a 10-year review.
AB  - Over the past 10 years, the field of health services and management research has
      seen renewed interest in the use of qualitative research methods. This article
      examines the volume and characteristics of qualitative research articles
      published in nine major health services and management journals between 1998 and
      2008. Qualitative research articles comprise 9% of research articles published in
      these journals. Although the publication rate of qualitative research articles
      has not kept pace with that of quantitative research articles, citation analysis
      suggests that qualitative research articles contribute comparably to the field's
      knowledge base. A wide range of policy and management topics has been examined
      using qualitative methods. Case study designs, interviews, and documentary
      sources were the most frequently used methods. Half of qualitative research
      articles provided little or no detail about key aspects the study's methods.
      Implications are discussed and recommendations are offered for promoting the
      publication of qualitative research.

PMID- 20675354
TI  - The influence of school-based natural mentoring relationships on school
      attachment and subsequent adolescent risk behaviors.
AB  - A relatively new area of research suggests that naturally occurring mentoring
      relationships may influence the development of adolescents by protecting against
      risk behaviors. Few studies have explored how these relationships function to
      reduce risk behavior among youth, especially in the school context. Based on
      previous research and theory, we proposed and tested a mediation model, which
      hypothesized that school attachment mediated the longitudinal association between
      school-based natural mentoring relationships and risk behaviors, including eight
      indicators of substance use and violence. Students (N = 3320) from 65 high
      schools across eight states completed a self-report questionnaire at baseline and
      1-year follow-up. The sample was comprised of youth with an average age of 14.8
      years and an almost equal percentage of females (53%) and males from various
      ethnic backgrounds. Tests for mediation were conducted in Mplus using path
      analysis with full information maximum likelihood procedures and models adjusted
      for demographic covariates and baseline level of the dependent variable. Results
      suggested that natural mentoring relationships had a protective indirect
      influence on all eight risk behaviors through its positive association on the
      school attachment mediator. Implications are discussed for strengthening the
      association between school-based natural mentoring and school attachment to
      prevent risk behaviors among youth.

PMID- 20675355
TI  - Conformational plasticity of RNA for target recognition as revealed by the 2.15 A
      crystal structure of a human IgG-aptamer complex.
AB  - Aptamers are short single-stranded nucleic acids with high affinity to target
      molecules and are applicable to therapeutics and diagnostics. Regardless of an
      increasing number of reported aptamers, the structural basis of the interaction
      of RNA aptamer with proteins is poorly understood. Here, we determined the 2.15 A
      crystal structure of the Fc fragment of human IgG1 (hFc1) complexed with an anti
      Fc RNA aptamer. The aptamer adopts a characteristic structure fit to hFc1 that is
      stabilized by a calcium ion, and the binding activity of the aptamer can be
      controlled many times by calcium chelation and addition. Importantly, the aptamer
      hFc1 interaction involves mainly van der Waals contacts and hydrogen bonds rather
      than electrostatic forces, in contrast to other known aptamer-protein complexes.
      Moreover, the aptamer-hFc1 interaction involves human IgG-specific amino acids,
      rendering the aptamer specific to human IgGs, and not crossreactive to other
      species IgGs. Hence, the aptamer is a potent alternative for protein A affinity
      purification of Fc-fusion proteins and therapeutic antibodies. These results
      demonstrate, from a structural viewpoint, that conformational plasticity and
      selectivity of an RNA aptamer is achieved by multiple interactions other than
      electrostatic forces, which is applicable to many protein targets of low or no
      affinity to nucleic acids.

PMID- 20675356
TI  - Genomic repertoires of DNA-binding transcription factors across the tree of life.
AB  - Sequence-specific transcription factors (TFs) are important to genetic regulation
      in all organisms because they recognize and directly bind to regulatory regions
      on DNA. Here, we survey and summarize the TF resources available. We outline the
      organisms for which TF annotation is provided, and discuss the criteria and
      methods used to annotate TFs by different databases. By using genomic TF
      repertoires from ~700 genomes across the tree of life, covering Bacteria, Archaea
      and Eukaryota, we review TF abundance with respect to the number of genes, as
      well as their structural complexity in diverse lineages. While typical eukaryotic
      TFs are longer than the average eukaryotic proteins, the inverse is true for
      prokaryotes. Only in eukaryotes does the same family of DNA-binding domain (DBD)
      occur multiple times within one polypeptide chain. This potentially increases the
      length and diversity of DNA-recognition sequence by reusing DBDs from the same
      family. We examined the increase in TF abundance with the number of genes in
      genomes, using the largest set of prokaryotic and eukaryotic genomes to date. As
      pointed out before, prokaryotic TFs increase faster than linearly. We further
      observe a similar relationship in eukaryotic genomes with a slower increase in
      TFs.

PMID- 20675357
TI  - Involvement of argonaute proteins in gene silencing and activation by RNAs
      complementary to a non-coding transcript at the progesterone receptor promoter.
AB  - Double-stranded RNAs that are complementary to non-coding transcripts at gene
      promoters can activate or inhibit gene expression in mammalian cells.
      Understanding the mechanism for modulating gene expression by promoter-targeted
      antigene RNAs (agRNAs) will require identification of the proteins involved in
      recognition. Previous reports have implicated argonaute (AGO) proteins, but
      identifications have differed with involvement of AGO1, AGO2, or both AGO1 and
      AGO2 being reported by different studies. The roles of AGO3 and AGO4 have not
      been investigated. Here, we examine the role of AGO 1-4 in gene silencing and
      activation of the progesterone receptor (PR) gene. Expression of AGO2 is
      necessary for efficient gene silencing or activation and AGO2 is recruited to the
      non-coding transcript that overlaps the promoter during both gene silencing and
      activation. Expression of AGO1, AGO3 and AGO4 are not necessary for gene
      silencing or activation nor are AGO1, AGO3, or AGO4 recruited to the target non
      coding transcript during gene activation. These data indicate that AGO2 is the
      primary AGO variant involved in modulating expression of PR by agRNAs.

PMID- 20675358
TI  - Silencing microRNA-34a inhibits chondrocyte apoptosis in a rat osteoarthritis
      model in vitro.
AB  - OBJECTIVE: miRNAs, which are non-coding RNAs, play a role in the pathogenesis of
      disease including OA. miRNA (miR)-34a is induced by p53, subsequently leading to
      cell apoptosis, which is one of the major factors in the pathogenesis of OA. The
      purpose of this study is to investigate the effect of silencing miR-34a on IL
      1beta-induced chondrocyte apoptosis in a rat OA model in vitro. METHODS: Locked
      nucleotide analogue (LNA)-modified miR-34a-specific anti-sense was transfected
      into rat chondrocyte monolayer culture. After that, IL-1beta was added to the
      chondrocytes to create an OA model in vitro. The effect of silencing miR-34a on
      the prevention of chondrocyte apoptosis was analysed by assessment of the
      expression levels of Col2a1 and iNOS, also through assessment of cell viability
      and TUNEL staining. RESULTS: The expression of miR-34a was significantly up
      regulated by IL-1beta. Silencing of miR-34a significantly prevented IL-1beta
      induced down-regulation of Col2a1, as well as IL-1beta-induced up-regulation of
      iNOS. Finally, MiR-34a inhibitor could also reduce TUNEL-positive cells.
      CONCLUSION: Silencing of miR-34a by LNA-modified anti-sense could effectively
      reduce rat chondrocyte apoptosis induced by IL-1beta. This present study revealed
      that silencing of miR-34a might develop a novel intervention for OA treatment
      through the prevention of cartilage degradation.

PMID- 20675359
TI  - Clinical experience with bosentan and sitaxentan in connective tissue disease
      associated pulmonary arterial hypertension.
AB  - OBJECTIVES: To report outcomes in patients with CTD-pulmonary arterial
      hypertension (CTD-PAH) in an observational cohort treated with bosentan or
      sitaxentan and determine whether differences would justify a randomized,
      controlled multicentre study in this subpopulation. METHODS: Patients with CTD
      PAH, diagnosed by right-heart catheter studies, were assigned to either bosentan
      or sitaxentan based on physician choice. All patients were followed up with
      repeat assessments and data were collected for the local registry database.
      RESULTS: The bosentan- (n = 32) and sitaxentan- (n = 22) treated groups had
      comparable haemodynamic and prognostic measures at baseline. Repeat haemodynamic
      assessments showed reductions in pulmonary vascular resistance with bosentan (-99
      dynes/s/cm(5), P < 0.01) and sitaxentan (-92 dynes/s/cm(5), P < 0.05). The 6-min
      walk distance improved at 3 months with sitaxentan (25 m, P < 0.05). N-terminal
      pro-B-type natriuretic peptide levels fell in the bosentan cohort at 6 months (
      70 pmol/l, P < 0.05) and 1 year (-83 pmol/l, P < 0.01). Haemoglobin fell with
      both drugs (at 3 months -0.5 g/dl bosentan, P < 0.05 and -0.9 g/dl sitaxentan, P
      < 0.005). Calculations of the difference in treatment effect did not demonstrate
      superiority of either therapy. The 1-year estimated clinical worsening event
      rates were high: 41% sitaxentan, 62% bosentan (P = 0.142), with serious event
      rates of 27 and 14% (P = 0.263, log-rank test), respectively. Six patients
      discontinued bosentan because of transaminase elevation within the first year.
      Estimated 1-year survival was similar in both groups and 96% overall. CONCLUSION:
      Both sitaxentan and bosentan appear effective in CTD-PAH, but the apparent
      additional benefit of sitaxentan reported from the open-label Sitaxentan To
      Relieve ImpaireD Exercise-2X study was not confirmed in this observational
      cohort. Although survival has improved, event rates continue to be substantial
      and CTD-PAH remains a therapeutic challenge.

PMID- 20675360
TI  - Assessment of the genotoxic potential of indirect chemical mutagens in HepaRG
      cells by the comet and the cytokinesis-block micronucleus assays.
AB  - Many chemical carcinogens require metabolic activation to form genotoxic
      compounds in human. Standard in vitro genotoxicity assays performed with
      activation systems, such as rat liver S9, are recognised to lead to a high number
      of false positives. The aim of this study was to evaluate the suitability of
      differentiated human hepatoma HepaRG cells as an in vitro model system for the
      detection of DNA damage induced by promutagens using the comet and the
      cytokinesis-block micronucleus assays. Several promutagens were tested, including
      aflatoxin B1 (AFB1), benzo[a]pyrene (B[a]P), acrylamide, N-nitrosodimethylamine
      (NDMA), cyclophosphamide (CPA), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine
      (PhIP) and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). Cytotoxicity of these
      compounds was assessed by measuring lactate dehydrogenase leakage. A 24 h
      exposure was generally needed to obtain an obvious positive response in
      differentiated HepaRG cells in the comet and in the cytokinesis-block
      micronucleus assays. Comet formation was observed with all compounds except IQ.
      B[a]P, CPA and AFB1 showed a dose-dependent increase in micronucleated cells,
      whereas no increase was observed with PhIP, IQ and acrylamide. These preliminary
      data on genotoxicity in differentiated HepaRG cells are promising but more
      chemicals must be tested to determine the ability of HepaRG cells to assess
      genotoxicity of chemicals in humans.

PMID- 20675361
TI  - Patients and providers view gout differently: a qualitative study.
AB  - OBJECTIVES: We sought to examine patients' and providers' views on the treatment
      of gout to better understand why management is suboptimal. METHODS: In-depth
      telephone interviews were conducted with gout patients (n = 26) who initiated
      treatment with a urate-lowering drug (ULD) in the previous 6 months and with
      providers who care for gout patients (n = 15). The interviews were audiotaped and
      transcribed verbatim. Using qualitative methods, results were analysed and themes
      were identified. Interviews focused on the acute management, chronic management
      and prevention and improvement strategies. RESULTS: Providers viewed the majority
      of patients as having excellent relief with non-steroidal anti-inflammatories,
      colchicine and glucocorticoids, while some patients felt these medications were
      ineffective. Providers felt that most patients had a good understanding of the
      rationale for ULD therapy and that patients responded well. Some patients felt
      ULDs triggered, worsened or had no impact on their disease. Most providers
      thought medication adherence was relatively good. Some patients reported
      discontinuing medications. Discontinuations were largely purposeful and due to
      clinical or financial concerns. Most providers thought they had adequate skills
      to teach disease self-management behaviours. Patients requested more information
      and longer visit times. CONCLUSIONS: Providers view gout as easily managed, while
      patients report challenges and purposeful non-adherence.

PMID- 20675362
TI  - Motivation and diabetes self-management.
AB  - OBJECTIVE: To examine the relationship between autonomous motivation and diabetes
      self-care activities among individuals with diabetes. METHODS: Seventy-seven
      individuals recruited from outpatient clinic registries (64% female, 77%
      Caucasian, mean age 63 years) completed measures of diabetes-related self-care
      (Summary of Diabetes Self-care Activities), motivation (Treatment Self-regulation
      Questionnaire), health literacy (Rapid Estimate of Adult Literacy in Medicine,
      Newest Vital Sign), health (SF-36v2), social support (Social Support Survey) and
      self-efficacy (Perceived Competence Scale). RESULTS: Autonomous motivation was
      the only variable significantly associated with maintaining diet (p<0.0001) and
      blood glucose testing (p<0.04) in regression analyses. No significant
      associations were identified for exercise. The variable of age approached
      significance (p = 0.06), with older individuals being less likely to have
      exercised in the past week. DISCUSSION: Individuals in this study had difficulty
      in maintaining self-care demands, especially exercise. Meeting recommended levels
      of self-care activity was challenging, even for patients with adequate levels of
      health literacy. Individuals with higher levels of autonomous motivation reported
      higher frequencies for maintaining diet and testing blood glucose, however, which
      supports the utility of Self-Determination Theory in promoting diabetes self
      care.

PMID- 20675363
TI  - Effects of smoking cues in movies on immediate smoking behavior.
AB  - INTRODUCTION: The objective of this study was to investigate the effect of
      smoking cues in movies on immediate smoking behavior. We tested whether smokers
      who are confronted with smoking characters in a movie smoke more cigarettes while
      watching than those confronted with non-smoking characters and whether this
      effect is less profound when smokers are more involved in the narrative (i.e.,
      transportation). METHOD: Using an experimental design, 60 daily smokers were
      assigned randomly to one of two movie conditions (smoking vs. non-smoking
      characters). Participants were exposed to a 72-min movie clip and were allowed to
      smoke while watching the movie. Transportation and smoking habits were assessed
      with a questionnaire afterward. RESULTS: The results showed a significant
      interaction effect between movie condition and transportation on immediate
      smoking behavior, indicating that smokers who were less transported smoked
      significantly more cigarettes when they were exposed to smoking characters
      compared with non-smoking characters. DISCUSSION: These results call for (a)
      increasing the awareness among people about the effect smoking cues in movies
      might have and (b) stricter control over smoking cues in movies.

PMID- 20675364
TI  - Cigarette smoking in middle age and a long-term risk of impaired activities of
      daily living: NIPPON DATA80.
AB  - INTRODUCTION: Few studies have reported the relationship between smoking in
      middle age and long-term risk of impaired activities of daily living (ADL).
      METHODS: We analyzed 2,276 men and women aged 47-59 years at the baseline survey
      of NIPPON DATA80 in 1980. At the follow-up survey in 1999, ADL was surveyed among
      1890 survivors. Multivariate-adjusted odds ratio (AOR) and 95% CI of impaired ADL
      or of composite outcome of either death or impaired ADL according to baseline
      smoking status were calculated by multiple logistic regression analyses. RESULTS:
      In 1999, 386 participants were dead, and 75 participants had impaired ADL.
      Compared with nonsmokers, AOR (95% CI) of impaired ADL was significantly higher
      in current smokers at baseline (odds ratio [OR] 2.11 [1.09-4.06]). Compared with
      nonsmokers, AOR of impaired ADL was higher as the number of cigarettes increased
      (OR 2.04 [1.02-4.06] for <20 cigarettes/day and OR 2.35 [0.94-5.88] for >20
      cigarettes/day; p for trend = .04). AOR of composite outcome for current smoking
      was 1.83 (1.37-2.41). DISCUSSION: Smoking in middle age would increase future
      risks of impaired ADL. Smoking cessation may be important to prevent future
      impairment of ADL as well as death.

PMID- 20675365
TI  - Defining "smoker": college student attitudes and related smoking characteristics.
AB  - INTRODUCTION: Less than half of college students who have smoked in the past
      month identify themselves as smokers. Thus, we examined (a) how college students
      define the term "smoker" and (b) how this definition impacts smoking behavior and
      attitudes. METHODS: We conducted 12 focus groups with a total of 73 college
      student smokers drawn from survey participants at two colleges in Minnesota (a
      two-year technical college and a four-year university). Each group was homogenous
      in terms of gender and school (two-year, four-year). RESULTS: The majority
      (56.2%) were female, 49.3% attended a 2-year college, and 32.9% were regular
      smokers (smoked > or = 25 of the last 30 days). Participants described a "smoker"
      in terms of (a) smoking frequency, ranging from smoking infrequently to smoking
      daily; (b) contextual factors, such that smoking alone indicates being a smoker
      rather than smoking at parties; (c) time since initiation; (d) whether one
      purchases cigarettes, such that "smokers" buy cigarettes while nonsmokers borrow
      them; (e) addiction and being able to quit without great effort; (f) whether
      smoking is habitual; and (g) personality and physical characteristic. These
      beliefs had implications on experiences in quitting smoking, motivation to quit,
      and perceived barriers. Many participants indicated confidence in being able to
      quit but believed that they were not "smokers" and thus did not need to quit.
      DISCUSSION: College students use a broad range of criteria to define who is a
      smoker. These criteria impact how motivated students are to quit smoking and
      their perception of needing to "quit smoking."

PMID- 20675366
TI  - Leishmania subtilisin is a maturase for the trypanothione reductase system and
      contributes to disease pathology.
AB  - Proteases are a ubiquitous group of enzymes that play key roles in the life cycle
      of parasites, in the host-parasite relationship, and in the pathogenesis of
      parasitic diseases. Furthermore, proteases are druggable targets for the
      development of new anti-parasitic therapy. The subtilisin protease (SUB; Clan SB,
      family S8) of Leishmania donovani was cloned and found to possess a unique
      catalytic triad. This gene was then deleted by gene knock-out, which resulted in
      reduced ability by the parasite to undergo promastigote to amastigote
      differentiation in vitro. Electron microscopy of SUB knock-out amastigotes
      revealed abnormal membrane structures, retained flagella, and increased
      binucleation. SUB-deficient Leishmania displayed reduced virulence in both
      hamster and murine infection models. Histology of spleens from SUB knock-out
      infected hamsters revealed the absence of psammoma body calcifications indicative
      of the granulomatous lesions that occur during Leishmania infection. To delineate
      the specific role of SUB in parasite physiology, two-dimensional gel
      electrophoresis was carried out on SUB(-/-) versus wild-type parasites. SUB knock
      out parasites showed altered regulation of the terminal peroxidases of the
      trypanothione reductase system. Leishmania and other trypanosomatids lack
      glutathione reductase, and therefore rely on the novel trypanothione reductase
      system to detoxify reactive oxygen intermediates and to maintain redox
      homeostasis. The predominant tryparedoxin peroxidases were decreased in SUB(-/-)
      parasites, and higher molecular weight isoforms were present, indicating altered
      processing. In addition, knock-out parasites showed increased sensitivity to
      hydroperoxide. These data suggest that subtilisin is the maturase for
      tryparedoxin peroxidases and is necessary for full virulence.

PMID- 20675367
TI  - Dual role of alpha-secretase cleavage in the regulation of gamma-secretase
      activity for amyloid production.
AB  - Processing of the amyloid precursor protein (APP) by beta- and gamma-secretases
      generates pathogenic beta-amyloid (Abeta) peptides associated with Alzheimer
      disease (AD), whereas cleavage of APP by alpha-secretases precludes Abeta
      formation. Little is known about the role of alpha-secretase cleavage in gamma
      secretase regulation. Here, we show that alpha-secretase-cleaved APP C-terminal
      product (alphaCTF) functions as an inhibitor of gamma-secretase. We demonstrate
      that the substrate inhibitory domain (ASID) within alphaCTF, which is bisected by
      the alpha-secretase cleavage site, contributes to this negative regulation
      because deleting or masking this domain turns alphaCTF into a better substrate
      for gamma-secretase. Moreover, alpha-secretase cleavage can potentiate the
      inhibitory effect of ASID. Inhibition of gamma-secretase activity by alphaCTF is
      observed in both in vitro and cellular systems. This work reveals an unforeseen
      role for alpha-secretase in generating an endogenous gamma-secretase inhibitor
      that down-regulates the production of Abeta. Deregulation of this feedback
      mechanism may contribute to the pathogenesis of AD.

PMID- 20675368
TI  - Tilapia hepcidin 2-3 peptide modulates lipopolysaccharide-induced cytokines and
      inhibits tumor necrosis factor-alpha through cyclooxygenase-2 and
      phosphodiesterase 4D.
AB  - The antimicrobial peptide, tilapia hepcidin (TH) 2-3, belongs to the hepcidin
      family, and its antibacterial function has been reported. Here, we examined the
      TH2-3-mediated regulation of proinflammatory cytokines in bacterial endotoxin
      lipopolysaccharide (LPS)-stimulated mouse macrophages. The presence of TH2-3 in
      LPS-stimulated cells reduced the amount of tumor necrosis factor (TNF)-alpha
      secretion. From a microarray, real-time polymerase chain reaction (PCR), and
      cytokine array studies, we showed down-regulation of the proinflammatory
      cytokines TNF-alpha, interleukin (IL)-1alpha, IL-1beta, IL-6, and the
      prostaglandin synthesis gene, cyclooxygenase (COX)-2, by TH2-3. Studies with the
      COX-2-specific inhibitor, melaxicam, and with COX-2-overexpressing cells
      demonstrated the positive regulation of TNF-alpha and negative regulation of cAMP
      degradation-specific phosphodiesterase (PDE) 4D by COX-2. In LPS-stimulated
      cells, TH2-3 acts like melaxicam and down-regulates COX-2 and up-regulates PDE4D.
      The reduction in intracellular cAMP by TH2-3 or melaxicam in LPS-stimulated cells
      supports the negative regulation of PDE4D by COX-2 and TH2-3. This demonstrates
      that the inhibition of COX-2 is among the mechanisms through which TH2-3 controls
      TNF-alpha release. At 1 h after treatment, the presence of TH2-3 in LPS
      stimulated cells had suppressed the induction of pERK1/2 and prevented the LPS
      stimulated nuclear accumulation of NF-kappaB family proteins of p65, NF-kappaB2,
      and c-Rel. In conclusion, TH2-3 inhibits TNF-alpha and other proinflammatory
      cytokines through COX-2-, PDE4D-, and pERK1/2-dependent mechanisms.

PMID- 20675369
TI  - Metabolomic profiling reveals biochemical pathways and biomarkers associated with
      pathogenesis in cystic fibrosis cells.
AB  - Cystic fibrosis (CF) is a life-shortening disease caused by a mutation in the
      cystic fibrosis transmembrane conductance regulator (CFTR) gene. To gain an
      understanding of the epithelial dysfunction associated with CF mutations and
      discover biomarkers for therapeutics development, untargeted metabolomic analysis
      was performed on primary human airway epithelial cell cultures from three
      separate cohorts of CF patients and non-CF subjects. Statistical analysis
      revealed a set of reproducible and significant metabolic differences between the
      CF and non-CF cells. Aside from changes that were consistent with known CF
      effects, such as diminished cellular regulation against oxidative stress and
      osmotic stress, new observations on the cellular metabolism in the disease were
      generated. In the CF cells, the levels of various purine nucleotides, which may
      function to regulate cellular responses via purinergic signaling, were
      significantly decreased. Furthermore, CF cells exhibited reduced glucose
      metabolism in glycolysis, pentose phosphate pathway, and sorbitol pathway, which
      may further exacerbate oxidative stress and limit the epithelial cell response to
      environmental pressure. Taken together, these findings reveal novel metabolic
      abnormalities associated with the CF pathological process and identify a panel of
      potential biomarkers for therapeutic development using this model system.

PMID- 20675371
TI  - Neuropilin-1 mediates divergent R-Smad signaling and the myofibroblast phenotype.
AB  - The transforming growth factor-beta (TGF-beta) superfamily is one of the most
      diversified cell signaling pathways and regulates many physiological and
      pathological processes. Recently, neuropilin-1 (NRP-1) was reported to bind and
      activate the latent form of TGF-beta1 (LAP-TGF-beta1). We investigated the role
      of NRP-1 on Smad signaling in stromal fibroblasts upon TGF-beta stimulation.
      Elimination of NRP-1 in stromal fibroblast cell lines increases Smad1/5
      phosphorylation and downstream responses as evidenced by up-regulation of
      inhibitor of differentiation (Id-1). Conversely, NRP-1 loss decreases Smad2/3
      phosphorylation and its responses as shown by down-regulation of alpha-smooth
      muscle actin (alpha-SMA) and also cells exhibit more quiescent phenotypes and
      growth arrest. Moreover, we also observed that NRP-1 expression is increased
      during the culture activation of hepatic stellate cells (HSCs), a liver resident
      fibroblast. Taken together, our data suggest that NRP-1 functions as a key
      determinant of the diverse responses downstream of TGF-beta1 that are mediated by
      distinct Smad proteins and promotes myofibroblast phenotype.

PMID- 20675370
TI  - FasL expression in activated T lymphocytes involves HuR-mediated stabilization.
AB  - A prolonged activation of the immune system is one of the main causes of
      hyperproliferation of lymphocytes leading to defects in immune tolerance and
      autoimmune diseases. Fas ligand (FasL), a member of the TNF superfamily, plays a
      crucial role in controlling this excessive lymphoproliferation by inducing
      apoptosis in T cells leading to their rapid elimination. Here, we establish that
      posttranscriptional regulation is part of the molecular mechanisms that modulate
      FasL expression, and we show that in activated T cells FasL mRNA is stable. Our
      sequence analysis indicates that the FasL 3'-untranslated region (UTR) contains
      two AU-rich elements (AREs) that are similar in sequence and structure to those
      present in the 3'-UTR of TNFalpha mRNA. Through these AREs, the FasL mRNA forms a
      complex with the RNA-binding protein HuR both in vitro and ex vivo. Knocking down
      HuR in HEK 293 cells prevented the phorbol 12-myristate 13-acetate-induced
      expression of a GFP reporter construct fused to the FasL 3'-UTR. Collectively,
      our data demonstrate that the posttranscriptional regulation of FasL mRNA by HuR
      represents a novel mechanism that could play a key role in the maintenance and
      proper functioning of the immune system.

PMID- 20675372
TI  - The L279P mutation of nuclear distribution gene C (NudC) influences its chaperone
      activity and lissencephaly protein 1 (LIS1) stability.
AB  - LIS1, a gene mutated in classical lissencephaly, plays essential roles in
      cytoplasmic dynein regulation, mitosis and cell migration. However, the
      regulation of LIS1 (lissencephaly protein 1) protein remains largely unknown.
      Genetic studies in Aspergillus nidulans have uncovered that the Nud (nuclear
      distribution) pathway is involved in the regulation of cytoplasmic dynein complex
      and a temperature-sensitive mutation in the nudC gene (L146P) greatly reduces the
      protein levels of NudF, an Aspergillus ortholog of LIS1. Here, we showed that
      L146 in Aspergillus NudC and its flanking region were highly conservative during
      evolution. The similar mutation in human NudC (L279P) obviously led to reduced
      LIS1 and cellular phenotypes similar to those of LIS1 down-regulation. To explore
      the underlying mechanism, we found that the p23 domain-containing protein NudC
      bound to the molecular chaperone Hsp90, which is also associated with LIS1.
      Inhibition of Hsp90 chaperone function by either geldanamycin or radicicol
      resulted in a decrease in LIS1 levels. Ectopic expression of Hsp90 partially
      reversed the degradation of LIS1 caused by overexpression of NudC-L279P.
      Furthermore, NudC was found to regulate the ATPase activity of Hsp90, which was
      repressed by the mutation of L279P. Interestingly, NudC itself was shown to
      possess a chaperone function, which also was suppressed by the L279P mutation.
      Together, these data suggest that NudC may be involved in the regulation of LIS1
      stability by its chaperone function.

PMID- 20675373
TI  - Stathmin and interfacial microtubule inhibitors recognize a naturally curved
      conformation of tubulin dimers.
AB  - Tubulin is able to switch between a straight microtubule-like structure and a
      curved structure in complex with the stathmin-like domain of the RB3 protein
      (T(2)RB3). GTP hydrolysis following microtubule assembly induces protofilament
      curvature and disassembly. The conformation of the labile tubulin heterodimers is
      unknown. One important question is whether free GDP-tubulin dimers are
      straightened by GTP binding or if GTP-tubulin is also curved and switches into a
      straight conformation upon assembly. We have obtained insight into the bending
      flexibility of tubulin by analyzing the interplay of tubulin-stathmin association
      with the binding of several small molecule inhibitors to the colchicine domain at
      the tubulin intradimer interface, combining structural and biochemical
      approaches. The crystal structures of T(2)RB3 complexes with the chiral R and S
      isomers of ethyl-5-amino-2-methyl-1,2-dihydro-3-phenylpyrido[3,4-b]pyrazin-7-yl
      carbamate, show that their binding site overlaps with colchicine ring A and that
      both complexes have the same curvature as unliganded T(2)RB3. The binding of
      these ligands is incompatible with a straight tubulin structure in microtubules.
      Analytical ultracentrifugation and binding measurements show that tubulin
      stathmin associations (T(2)RB3, T(2)Stath) and binding of ligands (R, S, TN-16,
      or the colchicine analogue MTC) are thermodynamically independent from one
      another, irrespective of tubulin being bound to GTP or GDP. The fact that the
      interfacial ligands bind equally well to tubulin dimers or stathmin complexes
      supports a bent conformation of the free tubulin dimers. It is tempting to
      speculate that stathmin evolved to recognize curved structures in unassembled and
      disassembling tubulin, thus regulating microtubule assembly.

PMID- 20675374
TI  - Erythrocyte tropomodulin isoforms with and without the N-terminal actin-binding
      domain.
AB  - Erythrocyte tropomodulin (E-Tmod or Tmod1) of 41 kDa is a tropomyosin (TM)
      binding protein that caps the slow-growing end of the actin filaments. Its N
      terminal half is flexible, whereas the C-terminal half has a single domain
      structure. E-Tmod/TM5 complex may function as a "molecular ruler" generating
      actin protofilaments of ~37 nm. Here we report the discovery of a short isoform
      of 29 kDa that lacks the N-terminal actin-binding domain (N-ABD) but retains the
      C-terminal actin-binding domain (C-ABD). E-Tmod29 can be generated by alternative
      splicing from an upstream promoter or by multiple transcriptional start sites
      from a downstream promoter. Promoter switching leads to a surge of E-Tmod41 in
      reticulocytes, which degrades quickly in the cytosol. We expressed recombinant
      isoforms in Escherichia coli and tested their binding toward TM5, G-actin, and F
      actin. Solid-phase binding assays show that, without the N-terminal 102 residues,
      E-Tmod29 binds to TM5 or G-actin more strongly than E-Tmod41 does, but barely
      binds to F-actin after TM5 binding. Differential bindings explain the distinct
      localizations of E-Tmod29 in the cytosol and E-Tmod41 on the membrane. Sequential
      bindings and immunofluorescent staining further suggest that 1) TM5 binding to E
      Tmod41 may open up the flexible N-terminal half, exposing N-ABD and unblocking C
      ABD; 2) N-ABD binds to F-actin and C-ABD binds to G-actin; and 3) F-actin binding
      to N-ABD may prevent G-actin from binding to C-ABD. E-Tmod29 may thus modulate
      the availability of TM5 and G-actin for E-Tmod41 to construct the protofilament
      based membrane skeletal network for circulating erythrocytes.

PMID- 20675375
TI  - Only one ATP-binding DnaX subunit is required for initiation complex formation by
      the Escherichia coli DNA polymerase III holoenzyme.
AB  - The DnaX complex (DnaX(3)deltadelta'chi psi) within the Escherichia coli DNA
      polymerase III holoenzyme serves to load the dimeric sliding clamp processivity
      factor, beta(2), onto DNA. The complex contains three DnaX subunits, which occur
      in two forms: tau and the shorter gamma, produced by translational frameshifting.
      Ten forms of E. coli DnaX complex containing all possible combinations of wild
      type or a Walker A motif K51E variant tau or gamma have been reconstituted and
      rigorously purified. DnaX complexes containing three DnaX K51E subunits do not
      bind ATP. Comparison of their ability to support formation of initiation
      complexes, as measured by processive replication by the DNA polymerase III
      holoenzyme, indicates a minimal requirement for one ATP-binding DnaX subunit.
      DnaX complexes containing two mutant DnaX subunits support DNA synthesis at about
      two-thirds the level of their wild-type counterparts. beta(2) binding (determined
      functionally) is diminished 12-30-fold for DnaX complexes containing two K51E
      subunits, suggesting that multiple ATPs must be bound to place the DnaX complex
      into a conformation with maximal affinity for beta(2). DNA synthesis activity can
      be restored by increased concentrations of beta(2). In contrast, severe defects
      in ATP hydrolysis are observed upon introduction of a single K51E DnaX subunit.
      Thus, ATP binding, hydrolysis, and the ability to form initiation complexes are
      not tightly coupled. These results suggest that although ATP hydrolysis likely
      enhances beta(2) loading, it is not absolutely required in a mechanistic sense
      for formation of functional initiation complexes.

PMID- 20675377
TI  - The sodium channel {beta}3-subunit induces multiphasic gating in NaV1.3 and
      affects fast inactivation via distinct intracellular regions.
AB  - Electrical excitability in neurons depends on the activity of membrane-bound
      voltage gated sodium channels (Na(v)) that are assembled from an ion conducting
      alpha-subunit and often auxiliary beta-subunits. The alpha-subunit isoform
      Na(v)1.3 occurs in peripheral neurons together with the Na(v) beta3-subunit, both
      of which are coordinately up-regulated in rat dorsal root ganglion neurons after
      nerve injury. Here we examine the effect of the beta3-subunit on the gating
      behavior of Na(v)1.3 using whole cell patch clamp electrophysiology in HEK-293
      cells. We show that beta3 depolarizes the voltage sensitivity of Na(v)1.3
      activation and inactivation and induces biphasic components of the inactivation
      curve. We detect both a fast and a novel slower component of inactivation, and we
      show that the beta3-subunit increases the fraction of channels inactivating by
      the slower component. Using CD and NMR spectroscopy, we report the first
      structural analysis of the intracellular domain of any Na(v) beta-subunit. We
      infer the presence of a region within the beta3-subunit intracellular domain that
      has a propensity to form a short amphipathic alpha-helix followed by a
      structurally disordered sequence, and we demonstrate a role for both of these
      regions in the selective stabilization of fast inactivation. The complex gating
      behavior induced by beta3 may contribute to the known hyperexcitability of
      peripheral neurons under those physiological conditions where expression of beta3
      and Na(v)1.3 are both enhanced.

PMID- 20675376
TI  - Distinct effects of voltage- and store-dependent calcium influx on stretch
      induced differentiation and growth in vascular smooth muscle.
AB  - Stretch of the vascular wall stimulates smooth muscle hypertrophy by activating
      the MAPK and Rho/Rho kinase (ROK) pathways. We investigated the role of calcium
      in this response. Stretch-stimulated expression of contractile and cytoskeletal
      proteins in mouse portal vein was inhibited at mRNA and protein levels by
      blockade of voltage-dependent Ca(2+) entry (VDCE). In contrast, blockade of store
      operated Ca(2+) entry (SOCE) did not affect smooth muscle marker expression but
      decreased global protein synthesis. Activation of VDCE caused membrane
      translocation of RhoA followed by phosphorylation of its downstream effectors
      LIMK-2 and cofilin-2. Stretch-activated cofilin-2 phosphorylation depended on
      VDCE but not on SOCE. VDCE was associated with increased mRNA expression of
      myocardin, myocyte enhancer factor (MEF) -2A and -2D, and smooth muscle marker
      genes, all of which depended on ROK activity. SOCE increased ERK1/2
      phosphorylation and c-Fos expression but had no effect on phosphorylation of LIMK
      2 and cofilin-2 or on myocardin and MEF2 expression. Knockdown of MEF2A or -2D
      eliminated the VDCE-induced activation of myocardin expression and increased
      basal c-Jun and c-Fos mRNA levels. These results indicate that MEF2 mediates VDCE
      dependent stimulation of myocardin expression via the Rho/ROK pathway. In
      addition, SOCE activates the expression of immediate-early genes, known to be
      regulated by MEF2 via Ca(2+)-dependent phosphorylation of histone deacetylases,
      but this mode of Ca(2+) entry does not affect the Rho/ROK pathway.
      Compartmentation of Ca(2+) entry pathways appears as one mechanism whereby
      extracellular and membrane signals influence smooth muscle phenotype regulation,
      with MEF2 as a focal point.

PMID- 20675378
TI  - An engineered alpha1 integrin-binding collagenous sequence.
AB  - Collagen is an extracellular matrix structural component that can regulate
      cellular processes through its interaction with the integrins, alpha1beta1,
      alpha2beta1, alpha10beta1, and alpha11beta1. Collagen-like proteins have been
      identified in a number of bacterial species. Here, we used Scl2 from
      Streptococcus pyogenes serotype M28 strain MGAS6274 as a backbone for the
      introduction of discrete integrin-binding sequences. The introduced sequences
      GLPGER, GFPGER, or GFPGEN did not affect triple helix stability of the Scl
      (Streptococcal collagen-like) protein. Using ELISA and surface plasmon resonance,
      we determined that Scl2(GLPGER) and Scl2(GFPGER) bound to recombinant human
      alpha1 and alpha2 I-domains in a metal ion-dependent manner and without a
      requirement for hydroxyproline. We predicted a novel and selective integrin
      binding sequence, GFPGEN, through the use of computer modeling and demonstrated
      that Scl2(GFPGEN) shows specificity toward the alpha1 I-domain and does not bind
      the alpha2 I-domain. Using C2C12 cells, we determined that intact integrins
      interact with the modified Scl2 proteins with the same selectivity as recombinant
      I-domains. These modified Scl2 proteins also acted as cell attachment substrates
      for fibroblast, endothelial, and smooth muscle cells. However, the modified Scl2
      proteins were unable to aggregate platelets. These results indicate that Scl2 is
      a suitable backbone for the introduction of mammalian integrin-binding sequences,
      and these sequences may be manipulated to individually target alpha1beta1 and
      alpha2beta1.

PMID- 20675379
TI  - Asn415 in the beta11-beta12 linker decreases proton-dependent desensitization of
      ASIC1.
AB  - Neurons of the mammalian nervous system express the proton-sensing ion channel
      ASIC1. Low concentrations of protons in the normal range of extracellular pH, pH
      7.4-7.3, shut the pore by a conformational transition referred as steady-state
      desensitization. Therefore, the potential of local acidification to open ASIC1
      relies on proton affinity for desensitization. This property is important
      physiologically and also can be exploited to develop strategies to increase or
      decrease the channel response to protons. In a previous study (Li, T., Yang, Y.,
      and Canessa, C. M. (2010) J. Biol. Chem. 285, 22706-22712), we found that Leu-85
      in the beta1-beta2 linker of the extracellular domain decreases the apparent
      proton affinity for steady-state desensitization and retards openings, slowing
      down the time course of the macroscopic currents. Here, we show that Asn-415 in
      the beta11-beta12 linker works together with the beta1-beta2 linker to stabilize
      a closed conformation that delays transition from the closed to the desensitized
      state. Substitutions of Asn-415 for Cys, Ser, or Gly render ASIC1 responsive to
      small increases in proton concentrations near the baseline physiological pH.

PMID- 20675380
TI  - Changes in accessibility of cytoplasmic substances to the pore associated with
      activation of the cystic fibrosis transmembrane conductance regulator chloride
      channel.
AB  - Opening of the cystic fibrosis transmembrane conductance regulator Cl(-) channel
      is dependent both on phosphorylation and on ATP binding and hydrolysis. However,
      the mechanisms by which these cytoplasmic regulatory factors open the Cl(-)
      channel pore are not known. We have used patch clamp recording to investigate the
      accessibility of cytoplasmically applied cysteine-reactive reagents to cysteines
      introduced along the length of the pore-lining sixth transmembrane region (TM6)
      of a cysteine-less variant of cystic fibrosis transmembrane conductance
      regulator. We find that methanethiosulfonate (MTS) reagents modify irreversibly
      cysteines substituted for TM6 residues Phe-337, Thr-338, Ser-341, Ile-344, Val
      345, Met-348, Ala-349, Arg-352, and Gln-353 when applied to the cytoplasmic side
      of open channels. However, the apparent rate of modification by internal [2
      sulfonatoethyl] methanethiosulfonate (MTSES), a negatively charged MTS reagent,
      is dependent on the activation state of the channels. In particular, cysteines
      introduced far along the axis of TM6 from the inside (T338C, S341C, I344C) showed
      no evidence of significant modification even after prolonged pretreatment of non
      activated channels with internal MTSES. In contrast, cysteines introduced closer
      to the inside of TM6 (V345C, M348C) were readily modified in both activated and
      non-activated channels. Access of a permeant anion, Au(CN)(2)(-), to T338C was
      similarly dependent upon channel activation state. The pattern of MTS
      modification we observe allows us to designate different pore-lining amino acid
      side chains to distinct functional regions of the channel pore. One logical
      interpretation of these findings is that cytoplasmic access to residues at the
      narrowest region of the pore changes concomitant with activation.

PMID- 20675381
TI  - Hrs controls sorting of the epithelial Na+ channel between endosomal degradation
      and recycling pathways.
AB  - Epithelial Na(+) absorption is regulated by Nedd4-2, an E3 ubiquitin ligase that
      reduces expression of the epithelial Na(+) channel (ENaC) at the cell surface.
      Defects in this regulation cause Liddle syndrome, an inherited form of
      hypertension. Previous work found that Nedd4-2 functions through two distinct
      effects on trafficking, enhancing both ENaC endocytosis and ENaC degradation in
      lysosomes. To investigate the mechanism by which Nedd4-2 targets ENaC to
      lysosomes, we tested the role of hepatocyte growth factor-regulated tyrosine
      kinase substrate (Hrs), a component of the endosomal sorting complexes required
      for transport (ESCRT)-0 complex. We found that alpha-, beta-, and gammaENaC each
      interact with Hrs. These interactions were enhanced by Nedd4-2 and were dependent
      on the catalytic function of Nedd4-2 as well as its WW domains. Mutation of ENaC
      PY motifs, responsible for inherited hypertension (Liddle syndrome), decreased
      Hrs binding to ENaC. Moreover, binding of ENaC to Hrs was reduced by
      dexamethasone/serum- and glucocorticoid-inducible kinase and cAMP, which are
      signaling pathways that inhibit Nedd4-2. Nedd4-2 bound to Hrs and catalyzed Hrs
      ubiquitination but did not alter Hrs protein levels. Expression of a dominant
      negative Hrs lacking its ubiquitin-interacting motif (Hrs-DeltaUIM) increased
      ENaC surface expression and current. This occurred through reduced degradation of
      the cell surface pool of proteolytically activated ENaC, which enhanced its
      recycling to the cell surface. In contrast, Hrs-DeltaUIM had no effect on
      degradation of uncleaved inactive channels. The data support a model in which
      Nedd4-2 induces binding of ENaC to Hrs, which mediates the sorting decision
      between ENaC degradation and recycling.

PMID- 20675382
TI  - CYR61 regulates BMP-2-dependent osteoblast differentiation through the
      {alpha}v{beta}3 integrin/integrin-linked kinase/ERK pathway.
AB  - Osteoporosis is one of the most common bone pathologies. A number of novel
      molecules have been reported to increase bone formation including cysteine-rich
      protein 61 (CYR61), a ligand of integrin receptor, but mechanisms remain unclear.
      It is known that bone morphogenetic proteins (BMPs), especially BMP-2, are
      crucial regulators of osteogenesis. However, the interaction between CYR61 and
      BMP-2 is unclear. We found that CYR61 significantly increases proliferation and
      osteoblastic differentiation in MC3T3-E1 osteoblasts and primary cultured
      osteoblasts. CYR61 enhances mRNA and protein expression of BMP-2 in a time- and
      dose-dependent manner. Moreover, CYR61-mediated proliferation and osteoblastic
      differentiation are significantly decreased by knockdown of BMP-2 expression or
      inhibition of BMP-2 activity. In this study we found integrin alpha(v)beta(3) is
      critical for CYR61-mediated BMP-2 expression and osteoblastic differentiation. We
      also found that integrin-linked kinase, which is downstream of the
      alpha(v)beta(3) receptor, is involved in CYR61-induced BMP-2 expression and
      subsequent osteoblastic differentiation through an ERK-dependent pathway. Taken
      together, our results show that CYR61 up-regulates BMP-2 mRNA and protein
      expression, resulting in enhanced cell proliferation and osteoblastic
      differentiation through activation of the alpha(v)beta(3) integrin/integrin
      linked kinase/ERK signaling pathway.

PMID- 20675383
TI  - Gain of cellular adaptation due to prolonged p53 impairment leads to functional
      switchover from p53 to p73 during DNA damage in acute myeloid leukemia cells.
AB  - Tumor suppressor p53 plays the central role in regulating apoptosis in response
      to genotoxic stress. From an evolutionary perspective, the activity of p53 has to
      be backed up by other protein(s) in case of any functional impairment of this
      protein, to trigger DNA damage-induced apoptosis in cancer cells. We adopted
      multiple experimental approaches to demonstrate that in p53-impaired cancer
      cells, DNA damage caused accumulation of p53 paralogue p73 via Chk-1 that
      strongly impacted Bax expression and p53-independent apoptosis. On the contrary,
      when p53 function was restored by ectopic expression, Chk-2 induced p53
      accumulation that in turn overshadowed p73 activity, suggesting an antagonistic
      interaction between p53 family members. To understand such interaction better,
      p53-expressing cells were impaired differentially for p53 activity. In wild-type
      p53-expressing cancer cells that were silenced for p53 for several generations,
      p73 was activated, whereas no such trend was observed when p53 was transiently
      silenced. Prolonged p53 interference, even in functional p53 settings, therefore,
      leads to the "gain of cellular adaptation" in a way that alters the cellular
      microenvironment in favor of p73 activation by altering p73-regulatory proteins,
      e.g. Chk1 activation and dominant negative p73 down-regulation. These findings
      not only unveil a hitherto unexplained mechanism underlying the functional
      switchover from p53 to p73, but also validate p73 as a promising and potential
      target for cancer therapy in the absence of functional p53.

PMID- 20675384
TI  - Pin1 associates with and induces translocation of CRTC2 to the cytosol, thereby
      suppressing cAMP-responsive element transcriptional activity.
AB  - Pin1 is a unique regulator, which catalyzes the conversion of a specific phospho
      Ser/Thr-Pro-containing motif in target proteins. Herein, we identified CRTC2 as a
      Pin1-binding protein by overexpressing Pin1 with Myc and FLAG tags in mouse
      livers and subsequent purification of the complex containing Pin1. The
      association between Pin1 and CRTC2 was observed not only in overexpression
      experiments but also endogenously in the mouse liver. Interestingly, Ser(136) in
      the nuclear localization signal of CRTC2 was shown to be involved in the
      association with Pin1. Pin1 overexpression in HepG2 cells attenuated forskolin
      induced nuclear localization of CRTC2 and cAMP-responsive element (CRE)
      transcriptional activity, whereas gene knockdown of Pin1 by siRNA enhanced both.
      Pin1 also associated with CRTC1, leading to their cytosol localization,
      essentially similar to the action of CRTC2. Furthermore, it was shown that CRTC2
      associated with Pin1 did not bind to CREB. Taken together, these observations
      indicate the association of Pin1 with CRTC2 to decrease the nuclear CBP.CRTC.CREB
      complex. Indeed, adenoviral gene transfer of Pin1 into diabetic mice improved
      hyperglycemia in conjunction with normalizing phosphoenolpyruvate carboxykinase
      mRNA expression levels, which is regulated by CRE transcriptional activity. In
      conclusion, Pin1 regulates CRE transcriptional activity, by associating with
      CRTC1 or CRTC2.

PMID- 20675385
TI  - By interacting with the C-terminal Phe of apelin, Phe255 and Trp259 in helix VI
      of the apelin receptor are critical for internalization.
AB  - Apelin is the endogenous ligand of the orphan seven-transmembrane domain (TM) G
      protein-coupled receptor APJ. Apelin is involved in the regulation of body fluid
      homeostasis and cardiovascular functions. We previously showed the importance of
      the C-terminal Phe of apelin 17 (K17F) in the hypotensive activity of this
      peptide. Here, we show either by deleting the Phe residue (K16P) or by
      substituting it by an Ala (K17A), that it plays a crucial role in apelin receptor
      internalization but not in apelin binding or in Galpha(i)-protein coupling. Then
      we built a homology three-dimensional model of the human apelin receptor using
      the cholecystokinin receptor-1 model as a template, and we subsequently docked
      K17F into the binding site. We visualized a hydrophobic cavity at the bottom of
      the binding pocket in which the C-terminal Phe of K17F was embedded by Trp(152)
      in TMIV and Trp(259) and Phe(255) in TMVI. Using molecular modeling and site
      directed mutagenesis studies, we further showed that Phe(255) and Trp(259) are
      key residues in triggering receptor internalization without playing a role in
      apelin binding or in Galpha(i)-protein coupling. These findings bring new
      insights into apelin receptor activation and show that Phe(255) and Trp(259), by
      interacting with the C-terminal Phe of the pyroglutamyl form of apelin 13 (pE13F)
      or K17F, are crucial for apelin receptor internalization.

PMID- 20675386
TI  - Stabilization of hypoxia-inducible factor-1alpha protein in hypoxia occurs
      independently of mitochondrial reactive oxygen species production.
AB  - The transcription factor hypoxia-inducible factor-1alpha (HIF-1alpha) is a master
      regulator of the cellular response to low oxygen. HIF-1alpha protein accumulates
      in hypoxia due to inhibition of prolyl hydroxylase enzymes, which under normoxic
      conditions use molecular oxygen to hydroxylate HIF-1alpha on two conserved
      proline residues (Pro(402) and Pro(564)), thus targeting the protein for 26 S
      proteasome-dependent degradation. A functional mitochondrial electron transport
      chain is known to be necessary for HIF-1alpha stabilization in hypoxia. It has
      been reported that reactive oxygen species (ROS), produced under hypoxia by
      complex III of the mitochondrial electron transport chain, play a critical role
      in the stabilization of the HIF-1alpha protein, possibly by directly inhibiting
      prolyl hydroxylase enzymes. In contrast, we found that ROS production by complex
      III is not required for hypoxia-induced HIF-1alpha stabilization. Thus,
      reestablishing mitochondrial oxygen consumption in the presence of a complex III
      inhibitor by using an artificial electron donor to complex IV or by
      overexpressing Ciona intestinalis alternative oxidase results in HIF-1alpha
      protein stabilization in hypoxia. Furthermore, five inhibitors that target
      different sites of the mitochondrial electron transport chain have similar
      effects on the HIF-1alpha protein half-life in hypoxia but vary in their effects
      on mitochondrial ROS production. Finally, ROS do not regulate prolyl hydroxylase
      activity directly. We conclude that HIF-1alpha protein stabilization in hypoxia
      occurs independently of mitochondrial ROS production. However, mitochondria can
      modulate the cellular hypoxic response through altered respiratory activity,
      likely by regulating the cellular oxygen availability.

PMID- 20675387
TI  - Drosophila p53 is required to increase the levels of the dKDM4B demethylase after
      UV-induced DNA damage to demethylate histone H3 lysine 9.
AB  - Chromatin undergoes a variety of changes in response to UV-induced DNA damage,
      including histone acetylation. In human and Drosophila cells, this response is
      affected by mutations in the tumor suppressor p53. In this work, we report that
      there is a global decrease in trimethylated Lys-9 in histone H3 (H3K9me3) in
      salivary gland cells in wild type flies in response to UV irradiation. In
      contrast, flies with mutations in the Dmp53 gene have reduced basal levels of
      H3K9me3, which are then increased after UV irradiation. The reduction of H3K9me3
      in response to DNA damage occurs preferentially in heterochromatin. Our
      experiments demonstrate that UV irradiation enhances the levels of Lys-9
      demethylase (dKDM4B) transcript and protein in wild type flies, but not in Dmp53
      mutant flies. Dmp53 binds to a DNA element in the dKdm4B gene as a response to UV
      irradiation. Furthermore, heterozygous mutants for the dKdm4B gene are more
      sensitive to UV irradiation; they are deficient in the removal of cyclobutane
      pyrimidine dimers, and the decrease of H3K9me3 levels following DNA damage is not
      observed in dKdm4B mutant flies. We propose that in response to UV irradiation,
      Dmp53 enhances the expression of the dKDM4B histone demethylase, which
      demethylates H3K9me3 preferentially in heterochromatin regions. This mechanism
      appears to be essential for the proper function of the nucleotide excision repair
      system.

PMID- 20675391
TI  - Government drops plans to extend smoking ban in England.

PMID- 20675388
TI  - Zmynd15 encodes a histone deacetylase-dependent transcriptional repressor
      essential for spermiogenesis and male fertility.
AB  - Spermatogenesis is a complex process through which male germ line stem cells
      undergo a multi-step differentiation program and sequentially become
      spermatogonia, spermatocytes, spermatids, and eventually spermatozoa. In this
      process, transcription factors act as switches that precisely regulate the
      expression of genes that in turn control the developmental program of male germ
      cells. Transcription factors identified to be essential for normal haploid gene
      expression all display transcription-activating effects and thus serve as the
      "on" switch for haploid gene expression. Here, we report that ZMYND15 acts as a
      histone deacetylase-dependent transcriptional repressor and controls normal
      temporal expression of haploid cell genes during spermiogenesis. Inactivation of
      Zmynd15 results in early activation of transcription of numerous important
      haploid genes including Prm1, Tnp1, Spem1, and Catpser3; depletion of late
      spermatids; and male infertility. ZMYND15 represents the first transcriptional
      repressor identified to be essential for sperm production and male fertility.

PMID- 20675392
TI  - Ectopic pregnancy.

PMID- 20675393
TI  - Investigating mildly abnormal serum aminotransferase values.

PMID- 20675394
TI  - Amiodarone-induced skin hyperpigmentation.

PMID- 20675395
TI  - Buying 'legal' recreational drugs does not mean that you are not breaking the
      law.
AB  - BACKGROUND: Recreational drug use in the UK is common; sources of recreational
      drugs are changing, with increasing purchase of legal highs from the Internet.
      Previous studies have shown that there is not consistency of active ingredient(s)
      in legal highs purchased from the Internet. AIM: The aim of this study was to
      determine the impact of the 16 April 2010 change to the Misuse of Drugs Act
      (1971) on the content of 'legal highs' purchased over the Internet and supplied
      within the UK. METHODS: Legal highs were purchased from a number of different
      Internet suppliers and the active ingredients determined by analysis undertaken
      within a Home Office approved and licensed laboratory set in a UK academic
      institution. The active ingredient(s) detected on screening were then compared to
      the UK legislation in force at the time of purchase to determine whether each
      individual 'legal' high was in fact legal or not. RESULTS: All 18 products
      purchased prior to the change in the UK legislation contained active ingredients
      that were legal under the Misuse of Drugs Act (1971) in force at that time. Six
      products were purchased and analysed after the changes to the UK Misuse of Drugs
      Act (1971) on the 16 April 2010. Five of the products contained information,
      either on the Internet site or the packaging, stating that the product contained
      legal substances; the final product did not specify the active ingredient and so
      purchasers would be unable to determine if this was truly a legal product. Five
      of the six products contained an active ingredient that is a Class B drug under
      the Misuse of Drugs Act (1971); the other product contained an unlicensed
      medicine not controlled under the Misuse of Drugs Act (1971). CONCLUSION: We have
      shown in this study that some drugs sold as 'legal' highs contain drugs that are
      controlled under the Misuse of Drugs Act (1971). Under current UK legislation,
      individuals purchasing legal highs that contained controlled drugs would be
      subject to the same penalties as if they had knowingly purchased a controlled
      drug. Dissemination of information on the harm associated with the use of legal
      highs should also inform individuals that they may be purchasing controlled
      substances and the potential legal consequences of this.

PMID- 20675396
TI  - Mephedrone use and associated adverse effects in school and college/university
      students before the UK legislation change.
AB  - BACKGROUND: Mephedrone is a synthetic cathinone that is commonly used as a
      recreational drug among those who attend nightclubs. There have been increasing
      reports of toxicity associated with its use and it was controlled as a Class B
      drug under the Misuse of Drugs Act (1971) in the UK on 16 April 2010. There has
      been a suggestion from media reports that mephedrone use is common in
      children/students but there is no data on the prevalence of its use among the
      general population. The aim of this study was to determine the prevalence and
      frequency of use of mephedrone among school and college/university aged
      individuals and to collect data on the sources of mephedrone and acute harm
      related to its use. METHODS: Data was collected using a questionnaire survey in
      schools, colleges and universities in the Tayside area of Scotland, UK in
      February 2010. RESULTS: A total of 1006 individuals completed the survey [501
      (49.8%) males and 505 (50.2%) females], of whom 349 classified their educational
      institute as a school and 657 as a college/university. Among them 205 (20.3%)
      reported previous use of mephedrone; 23.4% reported using only using mephedrone
      on one occasion previously, although 4.4% reported daily use. A total of 56% of
      those who had used mephedrone, reported at least one unwanted effect associated
      with its use. A total of 17.6% of users reported 'addiction or dependence'
      symptoms associated with their mephedrone use. A total of 48.8% of users sourced
      mephedrone from street level dealers, 10.7% from the Internet. CONCLUSION: We
      have shown in this study that the use of mephedrone among school and
      college/university students is common and that users found it easy to obtain.
      There was a high prevalence of unwanted effects associated with its use. Further
      work is needed to determine the impact of the recent changes in the UK
      legislation relating to mephedrone and other related cathinones and whether this
      has been effective in reducing the prevalence of mephedrone use.

PMID- 20675397
TI  - Cardiovascular and metabolic risk profiles in young and old patients with type 2
      diabetes.
AB  - BACKGROUND: Young patients (aged < 40 years) with type 2 diabetes (T2D) have a
      high lifetime risk of developing cardiovascular disease (CVD). However, little is
      known about the CVD risk profile of this cohort in the UK primary care setting.
      AIM: To determine CVD risk profile of young patients with T2D without CVD
      compared to older (aged >40 years) subjects. DESIGN: A cross-sectional study
      using The Health Improvement Network (THIN) database, which contains anonymized
      patient information from more than 300 general practices throughout England and
      Wales. METHODS: T2D subjects above the age of 18 years without previous CVD and
      not on lipid or blood pressure lowering therapy were randomly selected. Data on
      glycaemic control and CVD risk factors [weight, body mass index (BMI), lipid
      profile] were collected. RESULTS: A total of 49,919 patients with T2D were
      identified, of whom 2756 (0.5%) and 47,163 (99.5%) were aged below and above 40
      years, respectively. Despite being at least 30 years younger (mean age: early vs.
      later onset; 33.8 vs. 66.9 years, P < 0.001), the proportions of adverse CVD risk
      profiles for young patients were similar to the older cohort with T2D. For young
      vs. old patients: the prevalence of BMI >25: 84.4% vs. 85.3%, P = 0.77; total
      cholesterol >4 mmol/l: 53.4% vs. 53.8%, P = 0.76; systolic hypertension: 58.2 vs.
      58.4%, P = 0.36 and diastolic hypertension: 28.1 vs. 28.5%, P = 0.73). Glycaemic
      controls were similarly suboptimal between the two groups (mean HbA1c: young vs.
      old; 7.6% vs. 7.5%, P = 0.49). The prevalence of risk factor clustering were also
      similar between young vs. old patients with T2D. DISCUSSION: Young T2D subjects
      possess risk factors that confer high lifetime risk for macrovascular
      complications, and therefore merits aggressive cardioprotective treatment.

PMID- 20675398
TI  - Proteins associated with the size and expansion rate of the abdominal aortic
      aneurysm wall as identified by proteomic analysis.
AB  - OBJECTIVES: Identification of biomarkers for the natural history of abdominal
      aortic aneurysms (AAA) holds the key to non-surgical intervention and improved
      selection for AAA repair. We aimed to associate the basic proteomic composition
      of AAA wall tissue with the expansion rate and size in patients with AAA.
      METHODS: A proteomic approach was used, consisting of two-dimensional
      polyacrylamide gel electrophoresis (2D-PAGE) and mass spectrometry (MS) to
      identify differentially expressed proteins in AAA tissue. Relevant protein spots
      were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS).
      RESULTS: Spearman's correlation analysis revealed 16 protein spots were strongly
      correlated with AAA expansion rate (rho>+/-0.75). Nine protein spots were
      identified. Six protein spots showed correlation with AAA size (rho>+/-0.5).
      Three protein spots were identified: vitronectin with traces of calreticulin,
      albumin and a spot containing two proteins: collagen alpha-3(VI) chain and
      vitamin D binding protein. Interestingly, in our previous study vitronectin was
      shown to be down-regulated in a ruptured AAA group compared with non-ruptured
      AAA. Western blot analysis in the present study confirmed a correlation of
      vitronectin bands with AAA size in aortic aneurysm tissue. CONCLUSION: A
      proteomic approach seems valuable, and identified several candidates not
      previously associated with AAA. Larger studies are required to confirm the
      potential and clinical role of the identified proteins.

PMID- 20675399
TI  - Giant left atrial thrombus 17 years after orthotopic heart transplantation.
AB  - We present the case of a 66-year-old woman who underwent orthotopic heart
      transplantation 17 years earlier for dilated cardiomyopathy. After 7 years
      allograft coronary vasculopathy developed requiring coronary artery angioplasty.
      In year 15 postoperatively she experienced congestive heart failure and she
      became symptomatic requiring diuretics and digoxin treatment. In year 16
      postoperatively a routine coronary computed tomography (CT) angiography study
      revealed a giant thrombus in the left atrium. The patient had had no
      thromboembolic-related symptoms. Anticoagulation therapy was introduced and the
      patient has not presented any thromboembolic-related complication. As the
      symptoms of cardiac insufficiency worsened we decided to evaluate the patient for
      re-transplantation.

PMID- 20675400
TI  - Surgical outcomes of newly categorized peripheral T3 non-small cell lung cancers:
      comparisons between chest wall invasion and large tumors (>7 cm).
AB  - The prognosis for non-small cell lung cancer (NSCLC) with chest wall invasion can
      vary due to the heterogeneous nature of the cell population. Because NSCLC with
      large tumors (>7 cm) have been reclassified as T3, the applicability of the new
      designation must be evaluated. We reviewed 140 patients with chest wall T3 and 28
      patients with T3 NSCLC with large tumors, but no chest wall invasion who
      underwent resection at our institution. Among chest wall T3 patients, elderly T3
      patients (>=80 years old) who died within 42 months, patients with either lymph
      node or pulmonary metastasis, or patients with a large tumor (>7 cm) had poorer
      prognoses than those who had not. The survival rates for cases with chest wall T3
      and cases with a large tumor without chest wall invasion were not significantly
      different. NSCLC patients with chest wall T3 with lymph node, or pulmonary
      metastasis, or with a large tumor should be considered for further multimodal
      treatment with or without resection to enhance their survival time. Elderly
      patients with chest wall invasion may not be good candidates for resection. A
      large tumor is so aggressive that re-classification of large tumor cases as T3 is
      suitable.

PMID- 20675401
TI  - Laser-induced endothelial cell activation supports fibrin formation.
AB  - Laser-induced vessel wall injury leads to rapid thrombus formation in an animal
      thrombosis model. The target of laser injury is the endothelium. We monitored
      calcium mobilization to assess activation of the laser-targeted cells. Infusion
      of Fluo-4 AM, a calcium-sensitive fluorochrome, into the mouse circulation
      resulted in dye uptake in the endothelium and circulating hematopoietic cells.
      Laser injury in mice treated with eptifibatide to inhibit platelet accumulation
      resulted in rapid calcium mobilization within the endothelium. Calcium
      mobilization correlated with the secretion of lysosomal-associated membrane
      protein 1, a marker of endothelium activation. In the absence of eptifibatide,
      endothelium activation preceded platelet accumulation. Laser activation of human
      umbilical vein endothelial cells loaded with Fluo-4 resulted in a rapid increase
      in calcium mobilization associated cell fluorescence similar to that induced by
      adenosine diphosphate (10 MUM) or thrombin (1 U/mL). Laser activation of human
      umbilical vein endothelial cells in the presence of corn trypsin inhibitor
      treated human plasma devoid of platelets and cell microparticles led to fibrin
      formation that was inhibited by an inhibitory monoclonal anti-tissue factor
      antibody. Thus laser injury leads to rapid endothelial cell activation. The laser
      activated endothelial cells can support formation of tenase and prothrombinase
      and may be a source of activated tissue factor as well.

PMID- 20675402
TI  - Bag1 directly routes immature BCR-ABL for proteasomal degradation.
AB  - Degradation of BCR-ABL oncoproteins by heat shock protein 90 (Hsp90) inhibitors
      in chronic myelogenous leukemia is expected to overcome resistance to ABL
      tyrosine kinase inhibitors. However, the precise mechanisms still remain to be
      uncovered. We found that while c-Cbl E3 ligase induced ubiquitin-dependent
      degradation of mature and phosphorylated BCR-ABL proteins, another E3 ligase CHIP
      (carboxyl terminus of the Hsc70-interacting protein) degraded immature BCR-ABL
      proteins and efficiently suppressed BCR-ABL-dependent leukemic growth.
      Interestingly, Bag1 (Bcl-2-associated athanogene-1), a nucleotide exchange factor
      for Hsc70, directly bound BCR-ABL with a high affinity, which was enhanced by
      CHIP and Hsp90 inhibitors, inhibited by imatinib and competed with Hsc70. Bag1
      knockdown abrogated Hsp90 inhibitor-induced BCR-ABL degradation. Bag1 induced
      binding of immature BCR-ABL to proteasome. Expression of Bag1 induced BCR-ABL
      degradation and growth suppression in Ba/F3 cells when Hsc70 was knocked down
      with or without CHIP induction. CHIP appears to sort newly synthesized Hsp90
      unchaperoned BCR-ABL to the proteasome not only by inhibiting Hsc70 and thereby
      promoting Bag1 to bind BCR-ABL, but also by ubiquitinating BCR-ABL. Bag1 may
      direct CHIP/Hsc70-regulated protein triage decisions on BCR-ABL immediately after
      translation to the degradation pathway.

PMID- 20675403
TI  - Translational competence of ribosomes released from a premature termination codon
      is modulated by NMD factors.
AB  - In addition to their well-documented roles in the promotion of nonsense-mediated
      mRNA decay (NMD), yeast Upf proteins (Upf1, Upf2/Nmd2, and Upf3) also manifest
      translational regulatory functions, at least in vitro, including roles in
      premature translation termination and subsequent reinitiation. Here, we find that
      all upf Delta strains also fail to reinitiate translation after encountering a
      premature termination codon (PTC) in vivo, a result that led us to seek a
      unifying mechanism for all of these translation phenomena. Comparisons of the in
      vitro translational activities of wild-type (WT) and upf1 Delta extracts were
      utilized to test for a Upf1 role in post-termination ribosome reutilization.
      Relative to WT extracts, non-nucleased extracts lacking Upf1 had approximately
      twofold decreased activity for the translation of synthetic CAN1/LUC mRNA, a
      defect paralleled by fewer ribosomes per mRNA and reduced efficiency of the 60S
      joining step at initiation. These deficiencies could be complemented by purified
      FLAG-Upf1, or 60S subunits, and appeared to reflect diminished cycling of
      ribosomes from endogenous PTC-containing mRNAs to exogenously added synthetic
      mRNA in the same extracts. This hypothesis was tested, and supported, by
      experiments in which nucleased WT or upf1 Delta extracts were first challenged
      with high concentrations of synthetic mRNAs that were templates for either normal
      or premature translation termination and then assayed for their capacity to
      translate a normal mRNA. Our results indicate that Upf1 plays a key role in a
      mechanism coupling termination and ribosome release at a PTC to subsequent
      ribosome reutilization for another round of translation initiation.

PMID- 20675405
TI  - Drug metabolism and pharmacokinetics of 4-substituted methoxybenzoyl-aryl
      thiazoles.
AB  - Tubulins are some of the oldest and most extensively studied therapeutic targets
      for cancer. Although many tubulin polymerizing and depolymerizing agents are
      known, the search for improved agents continues. We screened a class of tubulins
      targeting small molecules and identified 4-(3,4,5-trimethoxybenzoyl)-2-phenyl
      thiazole (SMART-H) as our lead compound. SMART-H inhibited the proliferation of a
      variety of cancer cells in vitro, at subnanomolar IC(50), and in vivo, in nude
      mice xenografts, with near 100% tumor growth inhibition. Metabolic stability
      studies with SMART-H in liver microsomes of four species (mouse, rat, dog, and
      human) revealed half-lives between <5 and 30 min, demonstrating an interspecies
      variability. The clearance predicted based on in vitro data correlated well with
      in vivo clearance obtained from mouse, rat, and dog in vivo pharmacokinetic
      studies. SMART-H underwent four major metabolic processes, including ketone
      reduction, demethylation, combination of ketone reduction and demethylation, and
      hydroxylation in human liver microsomes. Metabolite identification studies
      revealed that the ketone and the methoxy groups of SMART-H were most labile and
      that ketone reduction was the dominant metabolism reaction in human liver
      microsomes. We designed and tested four derivatives of SMART-H to improve the
      metabolic stability. The oxime and hydrazide derivatives, replacing the ketone
      site, demonstrated a 2- to 3-fold improved half-life in human liver microsomes,
      indicating that our prediction regarding metabolic stability of SMART-H can be
      extended by blocking ketone reduction. These studies led us to the next
      generation of SMART compounds with greater metabolic stability and higher
      pharmacologic potency.

PMID- 20675404
TI  - Novel endoribonucleases as central players in various pathways of eukaryotic RNA
      metabolism.
AB  - For a long time it has been assumed that the decay of RNA in eukaryotes is mainly
      carried out by exoribonucleases, which is in contrast to bacteria, where
      endoribonucleases are well documented to initiate RNA degradation. In recent
      years, several as yet unknown endonucleases have been described, which has
      changed our view on eukaryotic RNA metabolism. Most importantly, it was shown
      that the primary eukaryotic 3' --> 5' exonuclease, the exosome complex has the
      ability to endonucleolytically cleave its physiological RNA substrates, and novel
      endonucleases involved in both nuclear and cytoplasmic RNA surveillance pathways
      were discovered concurrently. In addition, endoribonucleases responsible for long
      known processing steps in the maturation pathways of various RNA classes were
      recently identified. Moreover, one of the most intensely studied RNA decay
      pathways--RNAi--is controlled and stimulated by the action of different
      endonucleases. Furthermore, endoribonucleolytic cleavages executed by various
      enzymes are also the hallmark of RNA degradation and processing in plant
      chloroplasts. Finally, multiple context-specific endoribonucleases control
      qualitative and/or quantitative changes of selected transcripts under particular
      conditions in different eukaryotic organisms. The aim of this review is to
      discuss the impact of all of these discoveries on our current understanding of
      eukaryotic RNA metabolism.

PMID- 20675407
TI  - Combinatorial, site-specific requirement for heterochromatic silencing factors in
      the elimination of nucleosome-free regions.
AB  - High-resolution nucleosome occupancy maps of heterochromatic regions of wild-type
      and silencing-defective mutants of the fission yeast Schizosaccharomyces pombe
      revealed that heterochromatin induces the elimination of nucleosome-free regions
      (NFRs). NFRs associated with transcription initiation sites as well as those not
      associated with promoters are affected. We dissected the roles of the histone
      H3K9 methyltransferase Clr4 and the HP1 proteins Swi6 and Chp2, as well as the
      two catalytic activities of the SHREC histone deacetylase (HDAC)/ATPase effector
      complex. Strikingly, different DNA sites have distinct combinatorial requirements
      for these factors: Five classes of NFRs were identified that are eliminated by
      silencing factors through a mechanistic hierarchy governed by Clr4. The SHREC
      HDAC activity plays a major role in the elimination of class I-IV NFRs by
      antagonizing the action of RSC, a remodeling complex implicated in NFR formation.
      We propose that heterochromatin formation involves the deployment in several
      sequence-specific mechanisms to eliminate gaps between nucleosomes, thereby
      blocking access to the DNA.

PMID- 20675408
TI  - Disulfide bond acquisition through eukaryotic protein evolution.
AB  - Disulfide bonds play critical roles in protein stability and function. They are
      generally considered to be strongly conserved among species. Although there is
      compelling evidence in the literature for this conservation on a case-by-case
      basis, comparative genomic analyses of disulfide conservation have in the past
      been limited. By analyzing the conservation of all structurally validated
      disulfide bonds from the Protein Data Bank across 29 completely sequenced
      eukaryotic genomes, we observe elevated conservation of disulfide-bonded
      cysteines (half-cystines) compared with unpaired cysteines and other amino acids.
      Remarkably, half-cystines are even more conserved than tryptophan--the most
      conserved amino acid. Overall, once disulfide bonds are acquired in proteins,
      they are rarely lost. Moreover, the acquisition of disulfide bonds shows a strong
      positive correlation (R(2) = 0.74) with organismal complexity. Although the
      correlation weakens (R(2) = 0.59) when yeast is excluded from the analysis, this
      trend is still apparent when compared with the slightly negative correlation of
      unpaired cysteine acquisition with organismal complexity. The accrual of
      disulfide bonds is likely to reflect the demand for greater sophistication in
      protein function in complex species. Our findings provide further support for the
      increasing usage of cysteines in modern proteomes and suggest that there has been
      positive selection for disulfide bonds through eukaryotic evolution. Finally, we
      show that the acquisition of the functionally relevant disulfide bond in domain 2
      of the CD4 protein occurred independently in primates and rodents.

PMID- 20675406
TI  - Nf2/Merlin controls progenitor homeostasis and tumorigenesis in the liver.
AB  - The molecular signals that control the maintenance and activation of liver
      stem/progenitor cells are poorly understood, and the role of liver progenitor
      cells in hepatic tumorigenesis is unclear. We report here that liver-specific
      deletion of the neurofibromatosis type 2 (Nf2) tumor suppressor gene in the
      developing or adult mouse specifically yields a dramatic, progressive expansion
      of progenitor cells throughout the liver without affecting differentiated
      hepatocytes. All surviving mice eventually developed both cholangiocellular and
      hepatocellular carcinoma, suggesting that Nf2(-/-) progenitors can be a cell of
      origin for these tumors. Despite the suggested link between Nf2 and the
      Hpo/Wts/Yki signaling pathway in Drosophila, and recent studies linking the
      corresponding Mst/Lats/Yap pathway to mammalian liver tumorigenesis, our
      molecular studies suggest that Merlin is not a major regulator of YAP in liver
      progenitors, and that the overproliferation of Nf2(-/-) liver progenitors is
      instead driven by aberrant epidermal growth factor receptor (EGFR) activity.
      Indeed, pharmacologic inhibition of EGFR blocks the proliferation of Nf2(-/-)
      liver progenitors in vitro and in vivo, consistent with recent studies indicating
      that the Nf2-encoded protein Merlin can control the abundance and signaling of
      membrane receptors such as EGFR. Together, our findings uncover a critical role
      for Nf2/Merlin in controlling homeostasis of the liver stem cell niche.

PMID- 20675410
TI  - High rate of large-scale hemizygous deletions in asexually propagating Daphnia:
      implications for the evolution of sex.
AB  - The origin and maintenance of sex remains one of the most debated topics in
      evolutionary biology. Investigations of the molecular genetic consequences of
      asexuality, such as direct estimation of mutation and recombination rates in
      asexual lineages, are critical for explaining the prevalence of sex in nature. In
      this study, we use long-term mutation accumulation lines of asexually propagating
      Daphnia pulex and D. obtusa to examine the role of hemizygous deletion and
      ameiotic recombination (crossover and gene conversion) in the evolution of
      asexual taxa. Large-scale hemizygous deletions ranging from 2 to 30 kb are found
      to occur at a rate of 6.7 * 10(-5) locus(-1) generation(-1) in D. pulex, which is
      one order of magnitude higher than the rate of large-scale deletions in
      Saccharomyces cerevisiae and Drosophila melanogaster. A conservative estimate of
      gene conversion and crossing over in the apomictic germ line cells of Daphnia
      yields a rate of 3.3 * 10(-5) locus(-1) generation(-1). Our exceptionally high
      rate of large-scale segmental deletions suggests that the long-term survival of
      asexual Daphnia lineages is likely compromised by a high deleterious mutation
      pressure and that selection against deleterious mutations may play an important
      role in the evolution and maintenance of sex.

PMID- 20675409
TI  - A genomic portrait of human microsatellite variation.
AB  - Rapid advances in DNA sequencing and genotyping technologies are beginning to
      reveal the scope and pattern of human genomic variation. Although single
      nucleotide polymorphisms (SNPs) have been intensively studied, the extent and
      form of variation at other types of molecular variants remain poorly understood.
      Polymorphism at the most variable loci in the human genome, microsatellites, has
      rarely been examined on a genomic scale without the ascertainment biases that
      attend typical genotyping studies. We conducted a genomic survey of variation at
      microsatellites with at least three perfect repeats by comparing two complete
      genome sequences, the Human Genome Reference sequence and the sequence of J.
      Craig Venter. The genomic proportion of polymorphic loci was 2.7%, much higher
      than the rate of SNP variation, with marked heterogeneity among classes of loci.
      The proportion of variable loci increased substantially with repeat number.
      Repeat lengths differed in levels of variation, with longer repeat lengths
      generally showing higher polymorphism at the same repeat number. Microsatellite
      variation was weakly correlated with regional SNP number, indicating modest
      effects of shared genealogical history. Reductions in variation were detected at
      microsatellites located in introns, in untranslated regions, in coding exons, and
      just upstream of transcription start sites, suggesting the presence of selective
      constraints. Our results provide new insights into microsatellite mutational
      processes and yield a preview of patterns of variation that will be obtained in
      genomic surveys of larger numbers of individuals.

PMID- 20675411
TI  - A comparison of liver function after hepatectomy with inflow occlusion between
      sevoflurane and propofol anesthesia.
AB  - BACKGROUND: In this study, we compared liver function tests after hepatectomy
      with inflow occlusion as a function of propofol versus sevoflurane anesthesia.
      METHODS: One hundred patients undergoing elective liver resection with inflow
      occlusion were randomized into a sevoflurane group or a propofol group. General
      anesthesia was induced with 3 MUg/kg fentanyl, 0.2 mg/kg cisatracurium, and
      target-controlled infusion of propofol, set at a plasma target concentration of 4
      to 6 MUg/mL, or sevoflurane initially started at 8%. Anesthesia was maintained
      with target-controlled infusion of propofol (2-4 MUg/mL) or sevoflurane (1.5%
      2.5%). The primary end point was postoperative liver injury assessed by peak
      values of liver transaminases. RESULTS: Transaminase levels peaked between the
      first and the third postoperative day. Peak alanine aminotransferase was 504 and
      571 U/L in the sevoflurane group and the propofol group, respectively. Peak
      aspartate aminotransferase was 435 U/L after sevoflurane and 581 U/L in the
      propofol group. There were no significant differences in peak alanine
      aminotransferase or peak aspartate aminotransferase between groups. Other liver
      function tests including bilirubin and alkaline phosphatase, and peak values of
      white blood cell counts and creatinine, were also not different between groups.
      CONCLUSIONS: Sevoflurane and propofol anesthetics resulted in similar patterns of
      liver function tests after hepatectomy with inflow occlusion. These data suggest
      that the 2 anesthetics are equivalent in this clinical context.

PMID- 20675412
TI  - Case report: epidural hematoma nine days after removal of a labor epidural
      catheter.
AB  - Timely recognition and surgical decompression are crucial to minimize risk of
      permanent neurologic deficit from epidural hematoma. We present the case of a
      patient who developed acute back pain, sensory deficit, and ascending weakness 9
      days after removal of a labor epidural catheter. Magnetic resonance imaging
      revealed a heterogeneous fluid collection extending from C6-7 through the lumbar
      region, with cord deformity at T9-11. Decompression laminectomy was performed
      within 4 hours of symptom onset. Twelve hours later, her motor function had fully
      recovered. Subsequent anatomic and hematologic workup was inconclusive. This
      presentation is atypical given the delayed presentation of symptoms after
      epidural placement.

PMID- 20675413
TI  - The transition of children with disabilities to adulthood: what about dental
      care?

PMID- 20675414
TI  - Supplement at issue.

PMID- 20675415
TI  - Treating bell palsy.

PMID- 20675416
TI  - More about supplement.

PMID- 20675420
TI  - Controversial issues in treating the dental patient with autism.
AB  - BACKGROUND: The author conducted a literature review to investigate concerns that
      parents of a child with an autism spectrum disorder may have when oral health
      care is provided to the child. TYPES OF STUDIES REVIEWED: The author conducted a
      search of PubMed using the terms "mercury," "fluoride," "nitrous oxide,"
      "antibiotics," "gluten," "casein," "acetaminophen" and "dentistry" each with the
      term "autism." He identified controlled studies and literature reviews in both
      medical and alternative medical literature that were related to areas of
      importance to oral health care workers. The use of mercury, fluoride, nitrous
      oxide, antibiotic agents and acetaminophen all are sources of controversy between
      dentistry and the parents of children who have autism. RESULTS: The author found
      that patients who have autism frequently also have allergies, immune system
      problems, gastrointestinal disturbances and seizures. Dental health care workers
      must be aware of these comorbid conditions so they can provide optimal care to
      the children with autism spectrum disorders. The author found two distinct
      theories as to what causes autism: one that focuses on genetic causes, and one
      that focuses on the impact of the environment. He found that the interpretation
      of these theories might affect parents' concerns about various dental treatments.
      CLINICAL IMPLICATIONS: Dentists treating patients who have autism may need to
      provide more than standard patient care, as the use of time-tested dental
      treatment and prevention modalities may be questioned or refused by parents.

PMID- 20675421
TI  - The effect of antisialogogues in dentistry: a systematic review with a focus on
      bond failure in orthodontics.
AB  - BACKGROUND: The authors conducted a literature review to assess whether there is
      a reduction of salivation with the use of antisialogogues, whether the use of
      antisialogogues reduces the chair time needed for dental procedures and whether
      the use of antisialogogues reduces bond failure in orthodontics. METHODS: The
      authors conducted a search for original articles published from 1950 to April
      2010 by using the following databases: Cochrane Collaboration, PubMed, Scopus,
      EMBASE and ISI Web of Knowledge. They included in their review only human studies
      in which antisialogogues were used. They validated methodological quality and
      evidence grade. RESULTS: Twenty-six studies met the inclusion criteria. Twenty
      five of these studies were related to the effect of antisialogogues on
      salivation, and one study to bond failure. The authors found that there is
      evidence that antisialogogues work, inconclusive evidence that they reduce bond
      failure, and no evidence that they reduce chair time for dental procedures.
      CLINICAL IMPLICATIONS: Taking into account the systemic effects of
      antisialogogues, which exceed the time needed for bracket bonding, the use of
      antisialogogues for dental procedures in general is questionable.

PMID- 20675422
TI  - The use of platelet-rich plasma combined with demineralized freeze-dried bone
      allograft in the treatment of periodontal endosseous defects: a report of two
      clinical cases.
AB  - BACKGROUND: On the basis of systematic reviews and randomized controlled trials,
      the authors provide reports of two cases in which platelet-rich plasma (PRP)
      combined with demineralized freeze-dried bone allograft (DFDBA) was used to treat
      periodontal endosseous defects. CASE DESCRIPTION: Clinicians treated two
      circumferential endosseous defects with a probing pocket depth of 5 and 8
      millimeters, respectively (case 1), and a combined 1-2-3-wall endosseous defect
      with a probing pocket depth of 6 mm (case 2) by using the combination of PRP and
      DFDBA. At six months, complete periodontal pocket resolution occurred in all
      defects, and clinical attachment level and radiographic defect fill in all
      defects exhibited significant improvement compared with presurgical values.
      CLINICAL IMPLICATIONS: The combination of PRP and DFDBA may be clinically and
      radiographically efficacious in the treatment of periodontal endosseous defects.

PMID- 20675423
TI  - Gout of the temporomandibular joint: a review of the literature.
AB  - BACKGROUND: Gout is a common metabolic disorder that leads to elevated serum uric
      acid levels and deposition of urate crystals in tissues, leading to conditions
      such as arthritis and neuropathy. CASE DESCRIPTION: Although the prevalence of
      gout has been increasing during the past two decades, temporomandibular joint
      (TMJ) involvement is rare, with only 10 reports in the English-language
      literature. The authors present a rare case of gout involving the TMJ in a 51
      year-old woman. They also review reported cases of gout involving the TMJ,
      including the clinical, radiographic and microscopic diagnostic criteria. The
      patient was treated primarily with anti-inflammatory drugs and colchicine but
      refused to undergo surgery. To date, she continues to be free of symptoms despite
      the presence of gouty deposits. CLINICAL IMPLICATIONS: Because of its rarity, a
      clinician may overlook gout involving the TMJ in the differential diagnosis of
      facial pain even when the patient has received a diagnosis of gout in other
      joints.

PMID- 20675424
TI  - Dental care for pregnant women: an assessment of North Carolina general dentists.
AB  - BACKGROUND: The authors conducted a study to examine factors associated with
      general dentists' provision of care for pregnant women and the extent to which
      they provide comprehensive dental care. METHODS: The authors mailed an 86-item
      questionnaire to 1,000 practicing general dentists in North Carolina. Survey
      domains included provider knowledge about pregnancy and dental health, dental
      treatment practices, barriers to providing care, outcome expectancy, and personal
      and practice demographics. The primary dependent variables the authors analyzed
      were whether dentists provided any treatment to pregnant women and, among those
      who did, the extent to which they provided comprehensive services. The authors
      performed multivariate regression analyses to determine factors associated with
      dentists' provision of care to pregnant women (P < .05). RESULTS: A total of 513
      surveys were returned (a response rate of 51.3 percent), of which 495 surveys had
      complete responses. The authors included the completed surveys in their analyses.
      The mean age of the respondents was 46 years. The results of multivariate
      analysis showed that respondents who perceived a lack of demand for services
      among pregnant women and provided preconception counseling were less likely to
      provide any treatment for pregnant patients than were those who perceived a
      demand for services and who did not provide preconception counseling,
      respectively. Dentists who were male, had a low knowledge score, provided
      preconception counseling and treated largely white populations of patients were
      less likely than female dentists, those who had moderate or high knowledge
      scores, and those who treated a population of minority patients to provide
      comprehensive care for pregnant women. CONCLUSIONS: Most general dentists in
      private practice provide care for pregnant women, but the authors found notable
      gaps in dental provider knowledge and comprehensive dental services available for
      pregnant women. CLINICAL IMPLICATIONS: Although many general dentists provide
      some dental care to pregnant women, more should be done to ensure that this care
      is comprehensive.

PMID- 20675425
TI  - The effectiveness of a calcium sodium phosphosilicate desensitizer in reducing
      cervical dentin hypersensitivity: a pilot study.
AB  - BACKGROUND: NovaMin (NovaMin Technology, Alachua, Fla.) was introduced into the
      dental market as a desensitizer in December 2004. However, to the authors'
      knowledge, no researchers yet have evaluated the effectiveness of 100 percent
      NovaMin powder with NovaMin-containing toothpaste in reducing dentin
      hypersensitivity compared with the effectiveness of NovaMin-containing toothpaste
      only and a desensitizing toothpaste containing potassium nitrate as a control.
      METHODS: The authors divided 60 participants randomly into three groups: NovaMin
      powder with NovaMin-containing toothpaste (group 1), a placebo powder with
      NovaMin-containing toothpaste (group 2) and a placebo powder with the control
      toothpaste (group 3). The authors used tactile and cold stimuli and a visual
      analog scale to evaluate participants' pain at baseline, immediately after powder
      application and at one week, two weeks and four weeks after powder application.
      They analyzed data by using Friedman and Wilcoxon signed-rank tests for within
      group comparison. They used Kruskal-Wallis and Mann-Whitney U tests for between
      group comparison. They considered P < .05 to be statistically significant.
      RESULTS: Groups 1 and 2 showed significant hypersensitivity reduction over
      baseline at all time points. Group 3 showed significant hypersensitivity
      reduction at one week onward. Group 1 showed significant improvement compared
      with groups 2 and 3, except for response to tactile stimulus at four weeks with
      group 2. Between groups 2 and 3, there were significant differences at two and
      four weeks. CONCLUSIONS: and CLINICAL IMPLICATIONS: The use of NovaMin powder and
      NovaMin-containing toothpaste for hypersensitivity reduction is more effective
      than the use of a desensitizing toothpaste containing potassium nitrate and
      fluoride.

PMID- 20675426
TI  - Do faxed quitline referrals add value to dental office-based tobacco-use
      cessation interventions?
AB  - BACKGROUND: The Ask, Advise, Refer (AAR) model of intervening with patients who
      use tobacco promotes a brief office-based intervention plus referral to a tobacco
      quitline. However, there is little evidence that this model is effective. The
      primary aim of this study was to evaluate the effects on patients' tobacco use of
      two levels of a dental office-based intervention compared with usual care.
      METHODS: The authors randomly assigned 68 private dental clinics to one of three
      conditions: 5 As (Ask, Advise, Assess, Assist, Arrange); 3 As (AAR model); or
      usual care, and they enrolled 2,160 participants. RESULTS: At the 12-month
      assessment, compared with those in usual care, participants in the two
      intervention conditions combined were more likely to report cessation of tobacco
      use, as measured by nine-month prolonged abstinence (3 percent versus 2 percent;
      F(1,66) = 3.97, P < .10) and 12-month point prevalence (12 percent versus 8
      percent; F(1,66) = 7.32, P < .01). There were no significant differences between
      participants in the clinics using the 5 As and 3 As strategies. CONCLUSIONS: The
      results of this study are inconclusive as to whether referrals to a quitline add
      value to brief dental office-based interventions. Patients receiving telephone
      counseling quit tobacco use at higher rates, but only a small percentage of those
      proactively referred actually received counseling. CLINICAL IMPLICATIONS: The
      results confirm those of previous research: that training dental practitioners to
      provide brief tobacco-use cessation advice and assistance results in a change in
      their behavior, and that these practitioners are effective in helping their
      patients to quit using tobacco.

PMID- 20675427
TI  - Some evidence shows that certain mouthrinses can reduce halitosis.

PMID- 20675428
TI  - Adaptation of airline crew resource management principles to dentistry.
AB  - BACKGROUND: The aviation industry uses crew resource management (CRM) to address
      the human aspect of error. Dentistry can incorporate these concepts to reduce
      dental error. The authors provide a checklist to help clinicians mitigate error.
      METHODS: Health care systems have begun to focus on medical error. During the
      past 30 years, the airline industry has developed mitigation strategies that are
      being adapted for medicine. CRM involves the use of information, equipment and
      people to increase safety by targeting early identification of errors. RESULTS:
      To enhance safety, practitioners must implement forward-thinking strategies.
      Because human error is inevitable, threat and error management (TEM) techniques
      are needed to help identify and trap error before it develops into unexpected
      outcomes. Risk analysis increases situational awareness (SA) of potential dental
      error. Efficiency increases with early error detection. CONCLUSIONS: The authors
      provide a dental checklist that is divided into "appointment review," "before
      procedure," "procedure," "before dismissal" and "after dismissal" to organize
      dental activities in a manner that enhances error detection. PRACTICE
      IMPLICATIONS: The dental checklist is a tool to incorporate CRM and TEM
      techniques into the dental care environment to increase SA, safety and
      efficiency.

PMID- 20675429
TI  - The ceramic crown dilemma.

PMID- 20675430
TI  - Practice options for new dentists.

PMID- 20675431
TI  - What is the ethical course of action when a third-party payer denies coverage for
      a treatment I recommend simply because the treatment is not one of the plan's
      "evidence-based best practices"?

PMID- 20675433
TI  - Finding a balance: toward a substantive theory of employed mothers' personal and
      family health decision making.
AB  - PURPOSE: We investigated how mothers employed in support staff positions make
      personal and family health decisions. DESIGN: We used a critical feminist
      grounded theory design. METHODS: Twenty women employed at a large Canadian
      institution participated over two years in repeat interactive interviews.
      FINDINGS: "Finding a balance" was the emergent core process of health decision
      making in response to the basic social problem of multiple demands and
      uncoordinated, sometimes conflicting ideologies. Women emphasized recursive
      movement within a continuous process of four action phases: cueing in, figuring
      out, generating solutions, and assessing results. Two distinct views of finding a
      balance were revealed: weighing competing interests or harmonizing multiple
      interests. These distinctive views contributed to variation in women's approaches
      to decision making and to their personal and family health experiences.
      CONCLUSIONS: Women's experiences suggest a capacity for reflective practice in
      health decision making that provides an excellent basis for holistic,
      emancipatory nursing practice.

PMID- 20675432
TI  - Antinociceptive interactions between Mu-opioid receptor agonists and the
      serotonin uptake inhibitor clomipramine in rhesus monkeys: role of Mu agonist
      efficacy.
AB  - Mu-opioid agonists are effective analgesics but have undesirable effects such as
      sedation and abuse liability that limit their clinical effectiveness.
      Serotonergic systems also modulate nociception, and serotonin uptake inhibitors
      may be useful as adjuncts to enhance analgesic effects and/or attenuate
      undesirable effects of mu agonists. This study examined the effects of the
      serotonin uptake inhibitor clomipramine on behavioral effects produced in rhesus
      monkeys by mu agonists with varying efficacy at mu receptors (nalbuphine <
      morphine < methadone). Clomipramine and each mu agonist were studied alone and in
      fixed-proportion mixtures in assays of schedule-controlled responding, thermal
      nociception, and capsaicin-induced thermal allodynia. In the assay of schedule
      controlled responding, all mu agonists dose-dependently decreased response rates.
      Clomipramine was inactive alone and did not alter the effects of mu agonists. In
      the assay of thermal nociception, all mu agonists produced dose-dependent
      antinociception. Clomipramine was inactive alone but produced a proportion
      dependent enhancement of the antinociceptive effects of nalbuphine > morphine >
      methadone. In the assay of capsaicin-induced allodynia, nalbuphine produced dose
      dependent antiallodynia. Clomipramine alone was inactive, but as in the assay of
      thermal nociception, it produced a proportion-dependent enhancement in the
      effects of nalbuphine. These findings suggest that serotonin uptake inhibitors
      can selectively enhance the antinociceptive effects of mu agonists in nonhuman
      primates. These effects of serotonin uptake inhibitors may depend on the
      proportion of the serotonin uptake inhibitor and the efficacy of the mu agonist.
      The greatest enhancement was observed with intermediate proportions of
      clomipramine in combination with the low-efficacy mu agonist nalbuphine.

PMID- 20675434
TI  - CFTR and calcium-activated chloride channels in primary cultures of human airway
      gland cells of serous or mucous phenotype.
AB  - Using cell culture models, we have investigated the relative importance of cystic
      fibrosis transmembrane conductance regulator (CFTR) and calcium-activated
      chloride channels (CaCC) in Cl secretion by mucous and serous cells of human
      airway glands. In transepithelial recordings in Ussing chambers, the CFTR
      inhibitor CFTR(inh)-172 abolished 60% of baseline Cl secretion in serous cells
      and 70% in mucous. Flufenamic acid (FFA), an inhibitor of CaCC, reduced baseline
      Cl secretion by ~20% in both cell types. Methacholine and ATP stimulated Cl
      secretion in both cell types, which was largely blocked by treatment with 1,2
      bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) and partially by
      mucosal FFA or CFTR(inh)-172 with the exception of methacholine responses in
      mucous cells, which were not blocked by FFA and partially (~60%) by CFTR(inh)
      172. The effects of ionomycin on short-circuit current (I(sc)) were less than
      those of ATP or methacholine. Forskolin stimulated Cl secretion only if Cl in the
      mucosal medium was replaced by gluconate. In whole cell patch-clamp studies of
      single isolated cells, cAMP-induced Cl currents were ~3-fold greater in serous
      than mucous cells. Ionomycin-induced Cl currents were 13 times (serous) or 26
      times (mucous) greater than those generated by cAMP and were blocked by FFA. In
      serous cells, mRNA for transmembrane protein 16A (TMEM16A) was ~10 times more
      abundant than mRNA for CFTR. In mucous cells it was ~100 times more abundant. We
      conclude: 1) serous and mucous cells both make significant contributions to gland
      fluid secretion; 2) baseline Cl secretion in both cell types is mediated
      predominantly by CFTR, but CaCC becomes increasingly important after mediator
      induced elevations of intracellular Ca; and 3) the high CaCC currents seen in
      patch-clamp studies and the high TMEM16A expression in intact polarized cells
      sheets are not reflected in transepithelial current recordings.

PMID- 20675435
TI  - Bleomycin revisited: towards a more representative model of IPF?

PMID- 20675436
TI  - Did differences in mitochondrial properties influence the evolution of avian and
      mammalian lungs?

PMID- 20675437
TI  - Critical role for lactate dehydrogenase A in aerobic glycolysis that sustains
      pulmonary microvascular endothelial cell proliferation.
AB  - Pulmonary microvascular endothelial cells possess both highly proliferative and
      angiogenic capacities, yet it is unclear how these cells sustain the metabolic
      requirements essential for such growth. Rapidly proliferating cells rely on
      aerobic glycolysis to sustain growth, which is characterized by glucose
      consumption, glucose fermentation to lactate, and lactic acidosis, all in the
      presence of sufficient oxygen concentrations. Lactate dehydrogenase A converts
      pyruvate to lactate necessary to sustain rapid flux through glycolysis. We
      therefore tested the hypothesis that pulmonary microvascular endothelial cells
      express lactate dehydrogenase A necessary to utilize aerobic glycolysis and
      support their growth. Pulmonary microvascular endothelial cell (PMVEC) growth
      curves were conducted over a 7-day period. PMVECs consumed glucose, converted
      glucose into lactate, and acidified the media. Restricting extracellular glucose
      abolished the lactic acidosis and reduced PMVEC growth, as did replacing glucose
      with galactose. In contrast, slow-growing pulmonary artery endothelial cells
      (PAECs) minimally consumed glucose and did not develop a lactic acidosis
      throughout the growth curve. Oxygen consumption was twofold higher in PAECs than
      in PMVECs, yet total cellular ATP concentrations were twofold higher in PMVECs.
      Glucose transporter 1, hexokinase-2, and lactate dehydrogenase A were all
      upregulated in PMVECs compared with their macrovascular counterparts. Inhibiting
      lactate dehydrogenase A activity and expression prevented lactic acidosis and
      reduced PMVEC growth. Thus PMVECs utilize aerobic glycolysis to sustain their
      rapid growth rates, which is dependent on lactate dehydrogenase A.

PMID- 20675438
TI  - Lactococcus fujiensis sp. nov., a lactic acid bacterium isolated from vegetable
      matter.
AB  - Three strains of lactic acid bacteria, designated NJ 317(T), NJ 414 and NJ 415,
      were isolated from the outer leaves of Chinese cabbages (Brassica rapa L. var.
      glabra Regel) and characterized taxonomically. The strains were gram-reaction
      positive, catalase-negative, facultatively anaerobic cocci that did not produce
      gas from glucose and formed L-lactic acid. The major fatty acids were C(18 :
      1)omega9c, C(16 : 0), C(14 : 0) and summed feature 10. Morphological,
      physiological and phylogenetic data indicated that the strains belonged to the
      genus Lactococcus. These strains shared similar phenotypic characteristics and
      exhibited DNA relatedness values >96.6 % to each other, indicating that they
      represent a single species. The DNA G+C contents of the three strains were 42.1
      42.5 mol%. 16S rRNA gene sequences of the novel strains were determined and
      aligned with those of other species of the genus Lactococcus. On the basis of
      phylogenetic analysis the three strains grouped with other members of the genus
      Lactococcus. Lactococcus lactis and Lactococcus garvieae were the most closely
      related species, sharing a sequence similarity value of 94.4 % with the three
      strains. Ribotyping patterns, however, revealed that these strains were well
      separated from reference strains of species of the genus Lactococcus and DNA-DNA
      hybridization studies indicated that the novel strains had low levels (<20.2 %)
      of DNA relatedness with reference strains of L. lactis, L. garvieae and other
      type strains of previously described species, showing that they represent a
      different species. Based on this evidence, strains NJ 317(T), NJ 414 and NJ 415
      represent a novel species of the genus Lactococcus, for which the name
      Lactococcus fujiensis sp. nov. is proposed. The type strain is NJ 317(T) ( =
      JCM16395(T)  = CGMCC 1.10453(T)).

PMID- 20675439
TI  - Streptococcus porcorum sp. nov., isolated from domestic and wild pigs.
AB  - Seven isolates of an unidentified Gram-stain-positive, catalase-negative, coccus
      shaped organism isolated from domestic and wild pigs were characterized by
      phenotypic and molecular-genetic methods. Based on cellular morphology and
      biochemical criteria, the isolates were tentatively assigned to the genus
      Streptococcus, although the organisms did not appear to correspond to any
      recognized species. Comparative 16S rRNA gene sequencing showed that the unknown
      bacterium was phylogenetically closely related to, but distinct from,
      Streptococcus suis (97.5 % 16S rRNA gene sequence similarity to the type strain).
      rpoB and sodA sequence analysis showed minimum interspecies divergence from
      phylogenetically close 16S rRNA gene sequence-based relatives of 13.8 and 18.6 %,
      respectively. DNA-DNA hybridization of a strain of the unidentified organism
      demonstrated 8-18 % reassociation with S. suis NCTC 10234(T). The novel bacterium
      could be distinguished from S. suis and other Streptococcus species using
      biochemical tests. On the basis of phenotypic and phylogenetic evidence, it is
      proposed that the unknown isolates from domestic and wild animals be assigned to
      a novel species of the genus Streptococcus, Streptococcus porcorum sp. nov. The
      type strain is 682-03(T) ( = CCUG 58479(T)  = CECT 7593(T)).

PMID- 20675440
TI  - Primorskyibacter sedentarius gen. nov., sp. nov., a novel member of the class
      Alphaproteobacteria from shallow marine sediments.
AB  - Two gram-negative, aerobic, non-pigmented, non-motile, rod-shaped bacteria,
      strains KMM 9015 and KMM 9018(T), were isolated from a sample of shallow sediment
      collected from the Sea of Japan. An analysis of the nearly complete 16S rRNA gene
      sequences showed that the isolates were very close to each other phylogenetically
      (99.9 % sequence similarity) and their close relatives were Marinovum algicola
      FF3(T) (95.8 and 95.9 %, respectively) and members of the genera Leisingera (95.7
      95.1 and 95.8-95.2 %), Phaeobacter (95.0-94.2 and 95.1-94.2 %) and Thalassobius
      (96.3-94.8 and 96.2-94.7 %) of the class Alphaproteobacteria. In phylogenetic
      trees based on 16S rRNA gene sequences, strains KMM 9015 and KMM 9018(T) were
      positioned as a distinct phylogenetic line adjacent to Marinovum algicola. The
      major isoprenoid quinone was Q-10, the polar lipids consisted of
      phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol,
      diphosphatidylglycerol and an unknown lipid and the major fatty acid was C(18 :
      1)omega7c, followed by 11-methyl C(18 : 1)omega7c, in both strains. The DNA G+C
      contents of strains KMM 9015 and KMM 9018(T) were 60.2 and 61.9 mol%,
      respectively. Based on distinctive phenotypic characteristics and phylogenetic
      analysis, strains KMM 9015 and KMM 9018(T) represent a novel species in a novel
      genus, for which the name Primorskyibacter sedentarius gen. nov., sp. nov. is
      proposed. The type strain of Primorskyibacter sedentarius is strain KMM 9018(T) (
      = NRIC 0784(T)  = JCM 16874(T)).

PMID- 20675441
TI  - Photobacterium aphoticum sp. nov., isolated from coastal water.
AB  - A facultatively anaerobic marine gammaproteobacterium, designated strain M46(T),
      was isolated from Mediterranean seawater at Malvarrosa beach, Valencia, Spain.
      The strain was characterized by using a polyphasic approach and was found to be
      situated within the genus Photobacterium in the family Vibrionaceae. Phylogenetic
      analysis based on 16S rRNA gene sequences showed that strain M46(T) was closely
      related to P. rosenbergii CECT 7644(T), P. halotolerans CECT 5860(T) and P.
      ganghwense CECT 7641(T), showing sequence similarities of 96.8, 96.4 and 96.2 %,
      respectively. According to the results of phylogenetic analyses based on recA and
      gyrB gene sequences, the most closely related taxon was P. ganghwense CECT
      7641(T) with 87.4 and 85.0 % sequence similarity, respectively. Regardless of the
      gene used in phylogenetic analysis, strain M46(T) always formed a separate and
      stable clade containing these three species of the genus Photobacterium. Strain
      M46(T) was not luminescent and produced a diffusible brown pigment. It required
      NaCl to grow, reduced nitrate to nitrite and oxidized a small number of
      substrates in Biolog GN plates. Strain M46(T) was positive for arginine
      dihydrolase (ADH), beta-galactosidase, aesculin hydrolysis and DNase activity. In
      API ZYM tests, the novel strain was positive for alkaline phosphatase, leucine
      arylamidase and acidic phosphatase activities. The major cellular fatty acids
      were unsaturated C(18) and C(16), as in other members of the genus
      Photobacterium, but their relative amounts and the presence or absence of other
      fatty acids differentiated strain M46(T) from its closest relatives. Based on the
      results of this polyphasic taxonomic study, strain M46(T) represents a novel
      species of the genus Photobacterium, for which the name Photobacterium aphoticum
      is proposed. The type strain is M46(T) ( = CECT 7614(T)  = KCTC 23057(T)).

PMID- 20675442
TI  - Evolutionary dynamics of insertion sequences in relation to the evolutionary
      histories of the chromosome and symbiotic plasmid genes of Rhizobium etli
      populations.
AB  - Insertion sequences (IS) are mobile genetic elements that are distributed in many
      prokaryotes. In particular, in the genomes of the symbiotic nitrogen-fixing
      bacteria collectively known as rhizobia, IS are fairly abundant in plasmids or
      chromosomal islands that carry the genes needed for symbiosis. Here, we report an
      analysis of the distribution and genetic conservation of the IS found in the
      genome of Rhizobium etli CFN42 in a collection of 87 Rhizobium strains belonging
      to populations with different geographical origins. We used PCR to generate
      presence/absence profiles of the 39 IS found in R. etli CFN42 and evaluated
      whether the IS were located in consistent genomic contexts. We found that the IS
      from the symbiotic plasmid were frequently present in the analyzed strains,
      whereas the chromosomal IS were observed less frequently. We then examined the
      evolutionary dynamics of these strains based on a population genetic analysis of
      two chromosomal housekeeping genes (glyA and dnaB) and three symbiotic sequences
      (nodC and the two IS elements). Our results indicate that the IS contained within
      the symbiotic plasmid have a higher degree of genomic context conservation, lower
      nucleotide diversity and genetic differentiation, and fewer recombination events
      than the chromosomal housekeeping genes. These results suggest that the R. etli
      populations diverged recently in Mexico, that the symbiotic plasmid also had a
      recent origin, and that the IS elements have undergone a process of cyclic
      infection and expansion.

PMID- 20675443
TI  - Characterization of three mnp genes of Fomitiporia mediterranea and report of
      additional class II peroxidases in the order hymenochaetales.
AB  - We report the sequence-based characterization and expression patterns of three
      manganese peroxidase genes from the white rot fungus and grape vine pathogen
      Fomitiporia mediterranea (Agaricomycotina, Hymenochaetales), termed Fmmnp1,
      Fmmnp2, and Fmmnp3. The predicted open reading frames (ORFs) are 1,516-, 1,351-,
      and 1,345-bp long and are interrupted by seven, four, and four introns,
      respectively. The deduced amino acid sequences encode manganese peroxidases (EC
      1.11.1.13) containing 371, 369, and 371 residues, respectively, and are similar
      to the manganese peroxidases of the model white rot organism Phanerochaete
      chrysosporium. The expression of the genes is most likely differentially
      regulated, as revealed by real-time PCR analysis. Phylogenetic analysis reveals
      that other members of the order Hymenochaetales harbor mnp genes encoding
      proteins that are related only distantly to those of F. mediterranea.
      Furthermore, multiple partial lip- and mnp-like sequences obtained for Pycnoporus
      cinnabarinus (Agaricomycotina, Polyporales) suggest that lignin degradation by
      white rot taxa relies heavily on ligninolytic peroxidases and is not efficiently
      achieved by laccases only.

PMID- 20675444
TI  - Enhanced production of a plant monoterpene by overexpression of the 3-hydroxy-3
      methylglutaryl coenzyme A reductase catalytic domain in Saccharomyces cerevisiae.
AB  - Linalool production was evaluated in different Saccharomyces cerevisiae strains
      expressing the Clarkia breweri linalool synthase gene (LIS). The wine strain
      T(73) was shown to produce higher levels of linalool than conventional laboratory
      strains (i.e., almost three times the amount). The performance of this strain was
      further enhanced by manipulating the endogenous mevalonate (MVA) pathway:
      deregulated overexpression of the rate-limiting 3-hydroxy-3-methylglutaryl
      coenzyme A reductase (HMG-CoA reductase) doubled linalool production. In a
      haploid laboratory strain, engineering of this key step also improved linalool
      yield.

PMID- 20675445
TI  - The chitinolytic activity of Listeria monocytogenes EGD is regulated by
      carbohydrates but also by the virulence regulator PrfA.
AB  - Chitin, an insoluble polymer of N-acetyl-D-glucosamine (GlcNAc), is one of the
      most abundant carbohydrate polymers in marine and terrestrial environments.
      Chitin hydrolysis by Listeria monocytogenes depends on two chitinase-encoding
      genes, chiA and chiB, and the aim of this study was to investigate their
      regulation. Chitin induces the expression of both chitinases in late exponential
      growth phase, and chiA but not chiB is furthermore induced by the monomer GlcNAc.
      Furthermore, their expression is subjected to catabolite control. Chitinases
      expressed by bacterial pathogens have proven to be important not only for
      nutrient acquisition and environmental survival but also for infecting animals
      and humans. Interestingly, the central L. monocytogenes virulence gene regulator,
      PrfA, is required for the chitinolytic phenotype, as chitinase activity was
      significantly reduced in prfA mutant cells compared to its level in wild-type
      cells. In agreement with this, Northern blot analysis showed that the amounts of
      chiA and chiB transcripts upon induction by chitin were significantly lower in
      the prfA mutant than in the wild type. The chitinolytic activity and chiA and
      chiB expression were reduced in the absence of the sigB gene, indicating that
      sigma(B) is also important for the production of chitinases. The chiA, chiB, and
      chiA chiB mutants were not impaired for in vitro adhesion and invasion in
      epithelial cell lines, but the chiA chiB double mutant showed less survival
      ability in a chitin-enriched medium. The regulation of chitinolytic activity in
      L. monocytogenes is complex, and taken together, the results indicate that the
      biological role of this activity may not be limited to the external environment.

PMID- 20675446
TI  - Adaptation of methanogenic communities to the cofermentation of cattle excreta
      and olive mill wastes at 37 degrees C and 55 degrees C.
AB  - The acclimatization of methanogens to two-phase olive mill wastes (TPOMW) was
      investigated in pilot fermenters started up with cattle excreta (37 degrees C)
      and after changing their feed to excreta plus TPOMW (37 degrees C or 55 degrees
      C) or TPOMW alone (37 degrees C) until a steady state was reached (28 days).
      Methanogenic diversity was screened using a phylogenetic microarray (AnaeroChip),
      and positive targets were quantified by real-time PCR. Results revealed high
      phylogenetic richness, with representatives of three out of the four taxonomic
      orders found in digesters. Methanosarcina dominated in the starting excreta (>96%
      of total 16S rRNA gene copies; over 45 times more abundant than any other
      methanogen) at high acetate (0.21 g liter(-1)) and ammonia N concentrations (1.3
      g liter(-1)). Codigestion at 37 degrees C induced a 6-fold increase of
      Methanosarcina numbers, correlated with CH(4) production (r(Pearson) = 0.94; P =
      0.02). At 55 degrees C, the rise in temperature and H(2) partial pressure induced
      a burst of Methanobacterium, Methanoculleus, Methanothermobacter, and a group of
      uncultured archaea. The digestion of excreta alone resulted in low but constant
      biogas production despite certain oscillations in the methanogenic biomass.
      Unsuccessful digestion of TPOMW alone was attributed to high Cu levels inducing
      inhibition of methanogenic activity. In conclusion, the versatile Methanosarcina
      immediately adapted to the shift from excreta to excreta plus TPOMW and was
      responsible for the stimulated CH(4) production at 37 degrees C. Higher
      temperatures (55 degrees C) fostered methanogenic diversity by promoting some
      H(2) scavengers while yielding the highest CH(4) production. Further testing is
      needed to find out whether there is a link between increased methanogenic
      diversity and reactor productivity.

PMID- 20675447
TI  - Phenotypic characterization of Shewanella oneidensis MR-1 under aerobic and
      anaerobic growth conditions by using fourier transform infrared spectroscopy and
      high-performance liquid chromatography analyses.
AB  - Shewanella oneidensis is able to conserve energy for growth by reducing a wide
      variety of terminal electron acceptors during anaerobic respiration, including
      several environmentally hazardous pollutants. This bacterium employs various
      electron transfer mechanisms for anaerobic respiration, including cell-bound
      reductases and secreted redox mediators. The aim of this study was to develop
      rapid tools for profiling the key metabolic changes associated with these
      different growth regimes and physiological responses. Initial experiments focused
      on comparing cells grown under aerobic and anaerobic conditions. Fourier
      transform infrared (FT-IR) spectroscopy with cluster analysis showed that there
      were significant changes in the metabolic fingerprints of the cells grown under
      these two culture conditions. FT-IR spectroscopy clearly differentiated cells of
      S. oneidensis MR-1 cultured at various growth points and cells grown using
      different electron acceptors, resulting in different phenotypic trajectories in
      the cluster analysis. This growth-related trajectory analysis is applied
      successfully for the first time, here with FT-IR spectroscopy, to investigate the
      phenotypic changes in contrasting S. oneidensis cells. High-performance liquid
      chromatography (HPLC) was also used to quantify the concentrations of flavin
      compounds, which have been identified recently as extracellular redox mediators
      released by a range of Shewanella species. The partial least-squares regression
      (PLSR) multivariate statistical technique was combined with FT-IR spectroscopy to
      predict the concentrations of the flavins secreted by cells of S. oneidensis MR
      1, suggesting that this combination could be used as a rapid alternative to
      conventional chromatographic methods for analysis of flavins in cell cultures.
      Furthermore, coupling of the FT-IR spectroscopy and HPLC techniques appears to
      offer a potentially useful tool for rapid characterization of the Shewanella cell
      metabolome in various process environments.

PMID- 20675449
TI  - Modeling the effect of abrupt acid and osmotic shifts within the growth region
      and across growth boundaries on adaptation and growth of Listeria monocytogenes.
AB  - This study aims to model the effects of acid and osmotic shifts on the
      intermediate lag time of Listeria monocytogenes at 10 degrees C in a growth
      medium. The model was developed from data from a previous study (C. I. A.
      Belessi, Y. Le Marc, S. I. Merkouri, A. S. Gounadaki, S. Schvartzman, K. Jordan,
      E. H. Drosinos, and P. N. Skandamis, submitted for publication) on the effects of
      osmotic and pH shifts on the kinetics of L. monocytogenes. The predictive ability
      of the model was assessed on new data in milk. The effects of shifts were modeled
      through the dependence of the parameter h(0) ("work to be done" prior to growth)
      induced on the magnitude of the shift and/or the stringency of the new
      environmental conditions. For shifts across the boundary, the lag time was found
      to be affected by the length of time for which the microorganisms were kept at
      growth-inhibiting conditions. The predicted concentrations of L. monocytogenes in
      milk were overestimated when the effects of this shift were not taken into
      account. The model proved to be suitable to describe the effects of osmotic and
      acid shifts observed both within the growth domain and across the growth
      boundaries of L. monocytogenes.

PMID- 20675450
TI  - Restoration of growth phenotypes of Escherichia coli DH5alpha in minimal media
      through reversal of a point mutation in purB.
AB  - A point mutation (E115K) resulting in slower growth of Escherichia coli DH5alpha
      and XL1-Blue in minimal media was identified in the purB gene, coding for
      adenylosuccinate lyase (ASL), through complementation with an E. coli K-12
      genomic library and serial subcultures. Chromosomal modification reversing the
      mutation to the wild type restored growth phenotypes in minimal media.

PMID- 20675448
TI  - Identification of novel methane-, ethane-, and propane-oxidizing bacteria at
      marine hydrocarbon seeps by stable isotope probing.
AB  - Marine hydrocarbon seeps supply oil and gas to microorganisms in sediments and
      overlying water. We used stable isotope probing (SIP) to identify aerobic
      bacteria oxidizing gaseous hydrocarbons in surface sediment from the Coal Oil
      Point seep field located offshore of Santa Barbara, California. After incubating
      sediment with (13)C-labeled methane, ethane, or propane, we confirmed the
      incorporation of (13)C into fatty acids and DNA. Terminal restriction fragment
      length polymorphism (T-RFLP) analysis and sequencing of the 16S rRNA and
      particulate methane monooxygenase (pmoA) genes in (13)C-DNA revealed groups of
      microbes not previously thought to contribute to methane, ethane, or propane
      oxidation. First, (13)C methane was primarily assimilated by Gammaproteobacteria
      species from the family Methylococcaceae, Gammaproteobacteria related to
      Methylophaga, and Betaproteobacteria from the family Methylophilaceae. Species of
      the latter two genera have not been previously shown to oxidize methane and may
      have been cross-feeding on methanol, but species of both genera were heavily
      labeled after just 3 days. pmoA sequences were affiliated with species of
      Methylococcaceae, but most were not closely related to cultured methanotrophs.
      Second, (13)C ethane was consumed by members of a novel group of
      Methylococcaceae. Growth with ethane as the major carbon source has not
      previously been observed in members of the Methylococcaceae; a highly divergent
      pmoA-like gene detected in the (13)C-labeled DNA may encode an ethane
      monooxygenase. Third, (13)C propane was consumed by members of a group of
      unclassified Gammaproteobacteria species not previously linked to propane
      oxidation. This study identifies several bacterial lineages as participants in
      the oxidation of gaseous hydrocarbons in marine seeps and supports the idea of an
      alternate function for some pmoA-like genes.

PMID- 20675451
TI  - Requirement of the nitrogen starvation-induced protein Sll0783 for
      polyhydroxybutyrate accumulation in Synechocystis sp. strain PCC 6803.
AB  - Nitrogen is often a limiting nutrient in natural habitats. Therefore,
      cyanobacteria have developed multiple responses, which are controlled by
      transcription factor NtcA and the PII-signaling protein, to adapt to nitrogen
      deficiency. Transcriptional analyses of Synechocystis sp. strain PCC 6803 under
      nitrogen-deficient conditions revealed a highly induced gene (sll0783) which is
      annotated as encoding a conserved protein with an unknown function. This gene is
      part of a cluster of seven genes and has potential NtcA-binding sites in the
      upstream region. Homologues of this cluster occur in some unicellular,
      nondiazotrophic cyanobacteria and in several Alpha, Beta-, and
      Gammaproteobacteria, as well as in some Gram-positive bacteria. Most of the
      heterotrophic bacteria harboring this gene cluster are able to fix nitrogen and
      to produce polyhydroxybutyrate (PHB), whereas of the cyanobacteria, only
      Synechocystis sp. strain PCC 6803 can accumulate PHB. In this work, a
      Synechocystis sp. strain PCC 6803 sll0783 gene knockout mutant is characterized.
      This mutant is unable to accumulate PHB, a carbon and energy storage compound. In
      contrast, the levels of the carbon storage compound glycogen and the PHB
      precursor acetyl coenzyme A were similar to those of the wild type, indicating
      that the PHB-deficient phenotype does not likely result from a global deficiency
      in carbon metabolism. A specific deficiency in PHB synthesis was implied by the
      fact that the mutant exhibits impaired PHB synthase activity during prolonged
      nitrogen starvation. However, the expression of PHB synthase-encoding genes was
      not strongly affected in the mutant, suggesting that the impaired PHB synthase
      activity observed depends on a posttranscriptional process in which the product
      of sll0783 is involved.

PMID- 20675452
TI  - Effect of nitric oxide on anammox bacteria.
AB  - The effects of nitrogen oxides on anammox bacteria are not well known. Therefore,
      anammox bacteria were exposed to 3,500 ppm nitric oxide (NO) in the gas phase.
      The anammox bacteria were not inhibited by the high NO concentration but rather
      used it to oxidize additional ammonium to dinitrogen gas under conditions
      relevant to wastewater treatment.

PMID- 20675453
TI  - Interaction of Mycobacterium ulcerans with mosquito species: implications for
      transmission and trophic relationships.
AB  - Mycobacterium ulcerans is the causative agent of Buruli ulcer, a severe
      necrotizing skin disease that causes significant morbidity in Africa and
      Australia. Person-to-person transmission of Buruli ulcer is rare. Throughout
      Africa and Australia infection is associated with residence near slow-moving or
      stagnant water bodies. Although M. ulcerans DNA has been detected in over 30 taxa
      of invertebrates, fish, water filtrate, and plant materials and one environmental
      isolate cultured from a water strider (Gerridae), the invertebrate taxa
      identified are not adapted to feed on humans, and the mode of transmission for
      Buruli ulcer remains an enigma. Recent epidemiological reports from Australia
      describing the presence of M. ulcerans DNA in adult mosquitoes have led to the
      hypothesis that mosquitoes play an important role in the transmission of M.
      ulcerans. In this study we have investigated the potential of mosquitoes to serve
      as biological or mechanical vectors or as environmental reservoirs for M.
      ulcerans. Here we show that Aedes aegypti, A. albopictus, Ochlerotatus
      triseriatus, and Culex restuans larvae readily ingest wild-type M. ulcerans,
      isogenic toxin-negative mutants, and Mycobacterium marinum isolates and remain
      infected throughout larval development. However, the infections are not carried
      over into the pupae or adult mosquitoes, suggesting an unlikely role for
      mosquitoes as biological vectors. By following M. ulcerans through a food chain
      consisting of primary (mosquito larvae), secondary (predatory mosquito larva from
      Toxorhynchites rutilus septentrionalis), and tertiary (Belostoma species)
      consumers, we have shown that M. ulcerans can be productively maintained in an
      aquatic food web.

PMID- 20675454
TI  - Interplay between wheat cultivars, biocontrol pseudomonads, and soil.
AB  - There is a significant potential to improve the plant-beneficial effects of root
      colonizing pseudomonads by breeding wheat genotypes with a greater capacity to
      sustain interactions with these bacteria. However, the interaction between
      pseudomonads and crop plants at the cultivar level, as well as the conditions
      which favor the accumulation of beneficial microorganisms in the wheat
      rhizosphere, is largely unknown. Therefore, we characterized the three Swiss
      winter wheat (Triticum aestivum) cultivars Arina, Zinal, and Cimetta for their
      ability to accumulate naturally occurring plant-beneficial pseudomonads in the
      rhizosphere. Cultivar performance was measured also by the ability to select for
      specific genotypes of 2,4-diacetylphloroglucinol (DAPG) producers in two
      different soils. Cultivar-specific differences were found; however, these were
      strongly influenced by the soil type. Denaturing gradient gel electrophoresis
      (DGGE) analysis of fragments of the DAPG biosynthetic gene phlD amplified from
      natural Pseudomonas rhizosphere populations revealed that phlD diversity
      substantially varied between the two soils and that there was a cultivar-specific
      accumulation of certain phlD genotypes in one soil but not in the other.
      Furthermore, the three cultivars were tested for their ability to benefit from
      Pseudomonas inoculants. Interestingly, Arina, which was best protected against
      Pythium ultimum infection by inoculation with Pseudomonas fluorescens biocontrol
      strain CHA0, was the cultivar which profited the least from the bacterial
      inoculant in terms of plant growth promotion in the absence of the pathogen.
      Knowledge gained of the interactions between wheat cultivars, beneficial
      pseudomonads, and soil types allows us to optimize cultivar-soil combinations for
      the promotion of growth through beneficial pseudomonads. Additionally, this
      information can be implemented by breeders into a new and unique breeding
      strategy for low-input and organic conditions.

PMID- 20675455
TI  - Prolyl aminopeptidase from Streptomyces thermoluteus subsp. fuscus strain
      NBRC14270 and synthesis of proline-containing peptides by its S144C variant.
AB  - We specifically examined an exopeptidase, prolyl aminopeptidase (PAP), as a
      target for synthesis of proline-containing peptides. A PAP from Streptomyces
      thermoluteus subsp. fuscus NBRC14270 (PAP14270) was obtained using sequence-based
      screening. From PAP14270, 144Ser was replaced by Cys (scPAP14270) to give
      aminolysis activity. In contrast to wild-type PAP14270, scPAP14270 produced a
      polymer of proline benzyl ester and cyclo[Pro-Pro]. The product mass was
      confirmed using liquid chromatography-mass spectrometry (LC/MS). Several factors
      affecting the reaction, such as the pH, concentration of the substrate, and
      reaction time, were measured to determine their effects. Furthermore, a
      correlation was found between substrate specificity in proline peptide synthesis
      and the log D value of acyl acceptors in aminolysis catalyzed by scPAP14270.
      Results showed that dipeptide synthesis proceeded in a weakly acidic environment
      and that cyclization and polymerization occurred under alkaline conditions.
      Furthermore, results suggest that almost all amino acid esters whose log D value
      is greater than 0, except hydroxyproline benzyl ester (Hyp-OBzl), can be
      recognized as acyl acceptors. These findings support the use of PAPs as a tool
      for production of physiologically active proline peptides.

PMID- 20675456
TI  - Construction of self-transmissible green fluorescent protein-based biosensor
      plasmids and their use for identification of N-acyl homoserine-producing bacteria
      in lake sediments.
AB  - Many bacteria utilize quorum sensing (QS) systems to communicate with each other
      by means of the production, release, and response to signal molecules. N-Acyl
      homoserine lactone (AHL)-based QS systems are particularly widespread among the
      Proteobacteria, in which they regulate various functions. It has become evident
      that AHLs can also serve as signals for interspecies communication. However,
      knowledge on the impact of AHLs for the ecology of bacteria in their natural
      habitat is scarce, due mainly to the lack of tools that allow the study of QS in
      bacterial communities in situ. Here, we describe the construction of self
      mobilizable green fluorescent protein (GFP)-based AHL sensors that utilize the
      conjugation and replication properties of the broad-host-range plasmid RP4. We
      show that these novel AHL sensor plasmids can be easily transferred to different
      bacterial species by biparental mating and that they give rise to green
      fluorescent cells in case the recipient is an AHL producer. We also demonstrate
      that these sensor plasmids are capable of self-spreading within mixed biofilms
      and are a suitable tool for the identification of AHL-producing bacteria in lake
      sediment.

PMID- 20675457
TI  - Phagocytosis of Cryptococcus neoformans by, and nonlytic exocytosis from,
      Acanthamoeba castellanii.
AB  - Cryptococcus neoformans, an encapsulated, pathogenic yeast, is endowed with a
      variety of virulence factors, including a polysaccharide capsule. During
      mammalian infection, the outcome of the interaction between C. neoformans and
      macrophages is central to determining the fate of the host. Previous studies have
      shown similarities between the interaction of C. neoformans with macrophages and
      with amoebae, resulting in the proposal that fungal virulence for mammals
      originated from selection by amoeboid predators. In this study, we investigated
      the interaction of C. neoformans with the soil amoeba Acanthamoeba castellanii.
      Comparison of phagocytic efficiency of the wild type, nonencapsulated mutants,
      and complemented strains showed that the capsule was antiphagocytic for amoebae.
      Capsular enlargement was associated with a significant reduction in phagocytosis,
      suggesting that this phenomenon protects against ingestion by phagocytic
      predators. C. neoformans var. neoformans cells were observed to exit amoebae
      several hours after ingestion, in a process similar to the recently described
      nonlytic exocytosis from macrophages. Cryptococcal exocytosis from amoebae was
      dependent on the strain and on actin and required fungal viability. Additionally,
      the presence of a capsule was inversely correlated with the likelihood of
      extrusion in certain strains. In summary, nonlytic exocytosis from amoebae
      provide another parallel to observations in fungus-macrophage interactions. These
      results provide additional support for the notion that some mechanisms of
      virulence observed during mammalian infection originated, and were selected for,
      by environmental interactions.

PMID- 20675458
TI  - Mesophilic fermentation of renewable biomass: does hydraulic retention time
      regulate methanogen diversity?
AB  - The present long-term study (about 1,100 days) monitored the diversity of
      methanogens during the mesophilic, anaerobic digestion of beet silage. Six
      fermentor samples were analyzed by ribosomal RNA gene restriction analysis,
      fluorescence in situ hybridization, and fluorescence microscopy. Hydrogenotrophic
      methanogens dominated within the population in all samples analyzed.
      Multidimensional scaling revealed that a rapid decrease in hydraulic retention
      time resulted in increased species richness, which in turn led to slightly higher
      CH(4) yields.

PMID- 20675459
TI  - Cystic artery pseudo-aneurysm: a complication of xanthogranulomatous
      cholecystitis.
AB  - A 54-year-old man presented for radiology with pain and a feeling of fullness in
      the upper abdomen and an epigastric mass. Ultrasound revealed a large cystic mass
      with internal echoes, lying posterior and inferior to left lobe of the liver. The
      gallbladder was thick-walled and contracted, and contained a calculus and
      echogenic sludge. A cystic structure that produced swirling flow signals on
      colour Doppler was demonstrated within the gallbladder. The CT scan showed a
      thickened gallbladder with adjacent inflammation and a 2-cm pseudo-aneurysm in
      its wall. High-density material was present in the gallbladder lumen, in the
      extra-hepatic bile ducts and around the gastrohepatic ligament. A thick
      haemorrhagic pus, from which Escherichia coli was cultured, was drained from the
      gastrohepatic collection. An elective coeliac angiogram demonstrated a solitary
      pseudo-aneurysm of the medial branch of the cystic artery. Selective
      catheterisation of this artery with a micro-catheter enabled complete exclusion
      of the pseudo-aneurysm by a single micro-coil. Histological examination of the
      gallbladder, which was ultimately removed at open cholecystectomy, demonstrated
      xanthogranulomatous cholecystitis.

PMID- 20675460
TI  - False-positive radio-iodinated metaiodobenzylguanidine (123I-MIBG) accumulation
      in a mast cell-infiltrated infantile haemangioma.
AB  - Radio-iodinated metaiodobenzylguanidine ((123)I-MIBG) is used for the detection
      and staging of neuroblastoma, pheochromcytoma and other neuroendocrine tumours in
      diagnostic nuclear medicine. A specific uptake and storage mechanism provides the
      basis for imaging with (123)I-MIBG. Nevertheless, cases of false-positive (123)I
      MIBG scintigraphy with accumulation in non-chromaffin tumours have been
      described. Here, we present a case of a false-positive (123)I-MIBG scan in a case
      of a mast-cell infiltrated infantile haemangioma and discuss the possible uptake
      mechanism.

PMID- 20675461
TI  - 18F-FDG-PET-CT imaging findings of recurrent intracranial haemangiopericytoma
      with distant metastases.
AB  - A 42-year-old woman presented with local recurrence and distant lung and liver
      metastases 7 years after resection of a primary intracranial haemangiopericytoma.
      Whole-body (18)F-fluoro-2-deoxy-d-glucose (FDG)-positron emission tomography
      (PET)-CT scan showed no increased uptake in local recurrence or distant
      metastases except for a focus of increased FDG uptake within a hepatic
      metastasis. The hypermetabolic area correlated with an intratumoral hypoenhancing
      area on the CT scan. PET-CT scan may be useful to allow further understanding of
      the tumour.

PMID- 20675462
TI  - Mesenteric venous collateral vessels mimicking cystic pancreatic neoplasm.
AB  - We report an unusual case of intrapancreatic mesenteric venous collateral vessels
      following partial pancreatic surgical resection resembling pancreatic neoplasm
      upon greyscale sonographic and unenhanced CT examinations.

PMID- 20675463
TI  - Towards detecting the HER-2 receptor and metabolic changes induced by HER-2
      targeted therapies using medical imaging.
AB  - HER-2/neu (a receptor for human epidermal growth factor) is involved in cell
      survival, proliferation, angiogenesis and invasiveness. It is overexpressed in
      about 25% of breast cancers. Overexpression of HER-2 is associated with response
      to the anti-HER-2 antibody trastuzumab (herceptin). However, HER-2 expression can
      be heterogeneous within the primary tumour and can also exhibit discordant
      expression between a primary tumour and its metastases, bringing into question
      the practice of HER-2 screening to determine whether a patient is a candidate for
      trastuzumab using material obtained only from the primary tumour. Medical imaging
      modalities using HER-2-targeted tracers (or contrast agents) facilitate a global
      approach to the determination of HER-2 expression across all detectable tumour
      lesions, and could provide a more reliable indication of the patient's likely
      response to trastuzumab treatment. Here, I review the development and pre
      clinical (and occasional clinical) assessment of HER-2-targeted tracers. I
      discuss studies in which established imaging tracers, such as (11)C-choline, have
      been used to determine response to trastuzumab in a range of medical imaging
      modalities, including positron emission tomography (PET), single photon emission
      tomography (SPECT), MRI and optical imaging.

PMID- 20675465
TI  - Vascular neck bruit in a teenager.

PMID- 20675464
TI  - A new biodosimetric method: branched DNA-based quantitative detection of B1 DNA
      in mouse plasma.
AB  - A simple and accurate method for measuring the biological effects of radiation is
      of increasing importance, especially in mass casualty scenarios. We have
      therefore developed a new biodosimetric technique targeting circulating B1 DNA in
      mouse plasma by branched DNA signal amplification for rapid quantification of
      plasma DNA. This technology targets repetitive elements of the B1 retrotransposon
      in the mouse genome, followed by signal amplification using Panomics Quantigene
      2.0 reagents. Evaluation was conducted concerning precision, accuracy and
      linearity. Plasma samples were collected from mice 0-24 h after 0-10 Gy total
      body irradiation (TBI). The average inter- and intra-assay coefficients of
      variance were 8.7% and 12.3%, respectively. The average recovery rate of spiked
      DNA into plasma was 89.5%. This assay revealed that when BALB/c and NIH Swiss
      mice were exposed to 6 Gy TBI, plasma B1 DNA levels increased significantly at 3
      h post-TBI, peaked at 9 h and gradually returned toward baseline levels in 24 h.
      A dose-dependent change in plasma DNA was observed at 9 h post-TBI; the dose
      response relation was monotonic, exhibiting linearity for BALB/c mice from 3 to 6
      Gy (r = 0.993) and NIH Swiss mice from 3 to 7 Gy (r = 0.98). This branched DNA
      based assay is reliable, accurate and sensitive in detecting plasma B1 DNA
      quantitatively. A radiation dose-correlated increase in plasma B1 DNA was
      demonstrated in BALB/c and NIH Swiss mice in the dose range from 3 to 6 Gy,
      suggesting that plasma B1 DNA has potential as a biomarker for radiation
      biological effect.

PMID- 20675467
TI  - ICEEc2, a new integrative and conjugative element belonging to the pKLC102/PAGI-2
      family, identified in Escherichia coli strain BEN374.
AB  - The diversity of the Escherichia coli species is in part due to the large number
      of mobile genetic elements that are exchanged between strains. We report here the
      identification of a new integrative and conjugative element (ICE) of the
      pKLC102/PAGI-2 family located downstream of the tRNA gene pheU in the E. coli
      strain BEN374. Indeed, this new region, which we called ICEEc2, can be
      transferred by conjugation from strain BEN374 to the E. coli strain C600. We were
      also able to transfer this region into a Salmonella enterica serovar Typhimurium
      strain and into a Yersinia pseudotuberculosis strain. This transfer was then
      followed by the integration of ICEEc2 into the host chromosome downstream of a
      phe tRNA gene. Our data indicated that this transfer involved a set of three
      genes encoding DNA mobility enzymes and a type IV pilus encoded by genes present
      on ICEEc2. Given the wide distribution of members of this family, these mobile
      genetic elements are likely to play an important role in the diversification of
      bacteria.

PMID- 20675468
TI  - StyA1 and StyA2B from Rhodococcus opacus 1CP: a multifunctional styrene
      monooxygenase system.
AB  - Two-component flavoprotein monooxygenases are emerging biocatalysts that
      generally consist of a monooxygenase and a reductase component. Here we show that
      Rhodococcus opacus 1CP encodes a multifunctional enantioselective flavoprotein
      monooxygenase system composed of a single styrene monooxygenase (SMO) (StyA1) and
      another styrene monooxygenase fused to an NADH-flavin oxidoreductase (StyA2B).
      StyA1 and StyA2B convert styrene and chemical analogues to the corresponding
      epoxides at the expense of FADH2 provided from StyA2B. The StyA1/StyA2B system
      presents the highest monooxygenase activity in an equimolar ratio of StyA1 and
      StyA2B, indicating (transient) protein complex formation. StyA1 is also active
      when FADH2 is supplied by StyB from Pseudomonas sp. VLB120 or PheA2 from
      Rhodococcus opacus 1CP. However, in both cases the reductase produces an excess
      of FADH2, resulting in a high waste of NADH. The epoxidation rate of StyA1
      heavily depends on the type of reductase. This supports that the FADH2-induced
      activation of StyA1 requires interprotein communication. We conclude that the
      StyA1/StyA2B system represents a novel type of multifunctional flavoprotein
      monooxygenase. Its unique mechanism of cofactor utilization provides new
      opportunities for biotechnological applications and is highly relevant from a
      structural and evolutionary point of view.

PMID- 20675469
TI  - A novel replicative enzyme encoded by the linear Arthrobacter plasmid pAL1.
AB  - The soil bacterium Arthrobacter nitroguajacolicus Ru61a contains the linear
      plasmid pAL1, which codes for the degradation of 2-methylquinoline. Like other
      linear replicons of actinomycetes, pAL1 is characterized by short terminal
      inverted-repeat sequences and terminal proteins (TPpAL1) covalently attached to
      its 5' ends. TPpAL1, encoded by the pAL1.102 gene, interacts in vivo with the
      protein encoded by pAL1.101. Bioinformatic analysis of the pAL1.101 protein,
      which comprises 1,707 amino acids, suggested putative zinc finger and
      topoisomerase-primase domains and part of a superfamily 2 helicase domain in its
      N-terminal and central regions, respectively. Sequence motifs characteristic of
      the polymerization domain of family B DNA polymerases are partially conserved in
      a C-terminal segment. The purified recombinant protein catalyzed the
      deoxycytidylation of TPpAL1 in the presence of single-stranded DNA templates
      comprising the 3'-terminal sequence (5'-GCAGG-3'), which in pAL1 forms the
      terminal inverted repeat, but also at templates with 5'-(G/T)CA(GG/GC/CG)-3'
      ends. Enzyme assays suggested that the protein exhibits DNA topoisomerase, DNA
      helicase, and DNA- and protein-primed DNA polymerase activities. The pAL1.101
      protein, therefore, may act as a replicase of pAL1.

PMID- 20675470
TI  - The delta subunit of RNA polymerase, RpoE, is a global modulator of Streptococcus
      mutans environmental adaptation.
AB  - The delta subunit of RNA polymerase, RpoE, is widespread in low-G+C Gram-positive
      bacteria and is thought to play a role in enhancing transcriptional specificity
      by blocking RNA polymerase binding at weak promoter sites and stimulating RNA
      synthesis by accelerating core enzyme recycling. Despite the well-studied
      biochemical properties of RpoE, a role for this protein in vivo has not been
      defined in depth. In this study, we show that inactivation of rpoE in the human
      dental caries pathogen Streptococcus mutans causes impaired growth and loss of
      important virulence traits, including biofilm formation, resistance to
      antibiotics, and tolerance to environmental stresses. Complementation of the
      mutant with rpoE expressed in trans restored its phenotype to wild type. The
      luciferase fusion reporter showed that rpoE was highly transcribed throughout
      growth and that acid and hydrogen peroxide stresses repressed rpoE expression.
      Transcriptome profiling of wild-type and DeltarpoE cells in the exponential and
      early stationary phase of growth, under acid and hydrogen peroxide stress and
      under both stresses combined, revealed that genes involved in histidine
      synthesis, malolactic fermentation, biofilm formation, and antibiotic resistance
      were downregulated in the DeltarpoE mutant under all conditions. Moreover, the
      loss of RpoE resulted in dramatic changes in transport and metabolism of
      carbohydrates and amino acids. Interestingly, differential expression, mostly
      upregulation, of 330 noncoding regions was found. In conclusion, this study
      demonstrates that RpoE is an important global modulator of gene expression in S.
      mutans which is required for optimal growth and environmental adaptation.

PMID- 20675471
TI  - Unexpected abundance of coenzyme F(420)-dependent enzymes in Mycobacterium
      tuberculosis and other actinobacteria.
AB  - Regimens targeting Mycobacterium tuberculosis, the causative agent of
      tuberculosis (TB), require long courses of treatment and a combination of three
      or more drugs. An increase in drug-resistant strains of M. tuberculosis
      demonstrates the need for additional TB-specific drugs. A notable feature of M.
      tuberculosis is coenzyme F(420), which is distributed sporadically and sparsely
      among prokaryotes. This distribution allows for comparative genomics-based
      investigations. Phylogenetic profiling (comparison of differential gene content)
      based on F(420) biosynthesis nominated many actinobacterial proteins as candidate
      F(420)-dependent enzymes. Three such families dominated the results: the
      luciferase-like monooxygenase (LLM), pyridoxamine 5'-phosphate oxidase (PPOX),
      and deazaflavin-dependent nitroreductase (DDN) families. The DDN family was
      determined to be limited to F(420)-producing species. The LLM and PPOX families
      were observed in F(420)-producing species as well as species lacking F(420) but
      were particularly numerous in many actinobacterial species, including M.
      tuberculosis. Partitioning the LLM and PPOX families based on an organism's
      ability to make F(420) allowed the application of the SIMBAL (sites inferred by
      metabolic background assertion labeling) profiling method to identify F(420)
      correlated subsequences. These regions were found to correspond to flavonoid
      cofactor binding sites. Significantly, these results showed that M. tuberculosis
      carries at least 28 separate F(420)-dependent enzymes, most of unknown function,
      and a paucity of flavin mononucleotide (FMN)-dependent proteins in these
      families. While prevalent in mycobacteria, markers of F(420) biosynthesis
      appeared to be absent from the normal human gut flora. These findings suggest
      that M. tuberculosis relies heavily on coenzyme F(420) for its redox reactions.
      This dependence and the cofactor's rarity may make F(420)-related proteins
      promising drug targets.

PMID- 20675472
TI  - Dual biosynthesis pathway for longer-chain polyamines in the hyperthermophilic
      archaeon Thermococcus kodakarensis.
AB  - Long-chain and/or branched-chain polyamines are unique polycations found in
      thermophiles. Cytoplasmic polyamines were analyzed for cells cultivated at
      various growth temperatures in the hyperthermophilic archaeon Thermococcus
      kodakarensis. Spermidine [34] and N4-aminopropylspermine [3(3)43] were identified
      as major polyamines at 60 degrees C, and the amounts of N4-aminopropylspermine
      [3(3)43] increased as the growth temperature rose. To identify genes involved in
      polyamine biosynthesis, a gene disruption study was performed. The open reading
      frames (ORFs) TK0240, TK0474, and TK0882, annotated as agmatine ureohydrolase
      genes, were disrupted. Only the TK0882 gene disruptant showed a growth defect at
      85 degrees C and 93 degrees C, and the growth was partially retrieved by the
      addition of spermidine. In the TK0882 gene disruptant, agmatine and N1
      aminopropylagmatine accumulated in the cytoplasm. Recombinant TK0882 was purified
      to homogeneity, and its ureohydrolase characteristics were examined. It possessed
      a 43-fold-higher kcat/Km value for N1-aminopropylagmatine than for agmatine,
      suggesting that TK0882 functions mainly as N1-aminopropylagmatine ureohydrolase
      to produce spermidine. TK0147, annotated as spermidine/spermine synthase, was
      also studied. The TK0147 gene disruptant showed a remarkable growth defect at 85
      degrees C and 93 degrees C. Moreover, large amounts of agmatine but smaller
      amounts of putrescine accumulated in the disruptant. Purified recombinant TK0147
      possessed a 78-fold-higher kcat/Km value for agmatine than for putrescine,
      suggesting that TK0147 functions primarily as an aminopropyl transferase to
      produce N1-aminopropylagmatine. In T. kodakarensis, spermidine is produced mainly
      from agmatine via N1-aminopropylagmatine. Furthermore, spermine and N4
      aminopropylspermine were detected in the TK0147 disruptant, indicating that
      TK0147 does not function to produce spermine and long-chain polyamines.

PMID- 20675473
TI  - Mycobacterial biofilms facilitate horizontal DNA transfer between strains of
      Mycobacterium smegmatis.
AB  - Conjugal transfer of chromosomal DNA between strains of Mycobacterium smegmatis
      occurs by a novel mechanism. In a transposon mutagenesis screen, three transfer
      defective insertions were mapped to the lsr2 gene of the donor strain mc(2)155.
      Because lsr2 encodes a nonspecific DNA-binding protein, mutations of lsr2 give
      rise to a variety of phenotypes, including an inability to form biofilms. In this
      study, we show that efficient DNA transfer between strains of M. smegmatis occurs
      in a mixed biofilm and that the process requires expression of lsr2 in the donor
      but not in the recipient strain. Testing cells from different strata of standing
      cultures showed that transfer occurred predominantly at the biofilm air-liquid
      interface, as other strata containing higher cell densities produced very few
      transconjugants. These data suggest that the biofilm plays a role beyond mere
      facilitation of cell-cell contact. Surprisingly, we found that under standard
      assay conditions the recipient strain does not form a biofilm. Taking these
      results together, we conclude that for transfer to occur, the recipient strain is
      actively recruited into the biofilm. In support of this idea, we show that donor
      and recipient cells are present in almost equal numbers in biofilms that produce
      transconjugants. Our demonstration of genetic exchange between mycobacteria in a
      mixed biofilm suggests that conjugation occurs in the environment. Since biofilms
      are considered to be the predominant natural microhabitat for bacteria, our
      finding emphasizes the importance of studying biological and physical processes
      that occur between cells in mixed biofilms.

PMID- 20675474
TI  - NADP+ reduction with reduced ferredoxin and NADP+ reduction with NADH are coupled
      via an electron-bifurcating enzyme complex in Clostridium kluyveri.
AB  - It was recently found that the cytoplasmic butyryl-coenzyme A (butyryl-CoA)
      dehydrogenase-EtfAB complex from Clostridium kluyveri couples the exergonic
      reduction of crotonyl-CoA to butyryl-CoA with NADH and the endergonic reduction
      of ferredoxin with NADH via flavin-based electron bifurcation. We report here on
      a second cytoplasmic enzyme complex in C. kluyveri capable of energetic coupling
      via this novel mechanism. It was found that the purified iron-sulfur flavoprotein
      complex NfnAB couples the exergonic reduction of NADP+ with reduced ferredoxin
      (Fdred) and the endergonic reduction of NADP+ with NADH in a reversible reaction:
      Fdred2-+NADH+2 NADP++H+=Fdox+NAD++2 NADPH. The role of this energy-converting
      enzyme complex in the ethanol-acetate fermentation of C. kluyveri is discussed.

PMID- 20675475
TI  - Repair of DNA double-strand breaks following UV damage in three Sulfolobus
      solfataricus strains.
AB  - DNA damage repair mechanisms have been most thoroughly explored in the
      eubacterial and eukaryotic branches of life. The methods by which members of the
      archaeal branch repair DNA are significantly less well understood but have been
      gaining increasing attention. In particular, the approaches employed by
      hyperthermophilic archaea have been a general source of interest, since these
      organisms thrive under conditions that likely lead to constant chromosomal
      damage. In this work we have characterized the responses of three Sulfolobus
      solfataricus strains to UV-C irradiation, which often results in double-strand
      break formation. We examined S. solfataricus strain P2 obtained from two
      different sources and S. solfataricus strain 98/2, a popular strain for site
      directed mutation by homologous recombination. Cellular recovery, as determined
      by survival curves and the ability to return to growth after irradiation, was
      found to be strain specific and differed depending on the dose applied.
      Chromosomal damage was directly visualized using pulsed-field gel electrophoresis
      and demonstrated repair rate variations among the strains following UV-C
      irradiation-induced double-strand breaks. Several genes involved in double-strand
      break repair were found to be significantly upregulated after UV-C irradiation.
      Transcript abundance levels and temporal expression patterns for double-strand
      break repair genes were also distinct for each strain, indicating that these
      Sulfolobus solfataricus strains have differential responses to UV-C-induced DNA
      double-strand break damage.

PMID- 20675476
TI  - Antimicrobial peptides activate the Rcs regulon through the outer membrane
      lipoprotein RcsF.
AB  - Salmonella enterica species are exposed to envelope stresses due to their
      environmental and infectious lifestyles. Such stresses include amphipathic
      cationic antimicrobial peptides (CAMPs), and resistance to these peptides is an
      important property for microbial virulence for animals. Bacterial mechanisms used
      to sense and respond to CAMP-induced envelope stress include the RcsFCDB
      phosphorelay, which contributes to survival from polymyxin B exposure. The Rcs
      phosphorelay includes two inner membrane (IM) proteins, RcsC and RcsD; the
      response regulator RcsB; the accessory coregulator RcsA; and an outer membrane
      bound lipoprotein, RcsF. Transcriptional activation of the Rcs regulon occurred
      within minutes of exposure to CAMP and during the first detectable signs of CAMP
      induced membrane disorder. Rcs transcriptional activation by CAMPs required RcsF
      and preservation of its two internal disulfide linkages. The rerouting of RcsF to
      the inner membrane or its synthesis as an unanchored periplasmic protein resulted
      in constitutive activation of the Rcs regulon and RcsCD-dependent
      phosphorylation. These findings suggest that RcsFCDB activation in response to
      CAMP-induced membrane disorder is a result of a change in structure or
      availability of RcsF to the IM signaling constituents of the Rcs phosphorelay.

PMID- 20675477
TI  - Pyruvate is synthesized by two pathways in pea bacteroids with different
      efficiencies for nitrogen fixation.
AB  - Nitrogen fixation in legume bacteroids is energized by the metabolism of
      dicarboxylic acids, which requires their oxidation to both oxaloacetate and
      pyruvate. In alfalfa bacteroids, production of pyruvate requires NAD+ malic
      enzyme (Dme) but not NADP+ malic enzyme (Tme). However, we show that Rhizobium
      leguminosarum has two pathways for pyruvate formation from dicarboxylates
      catalyzed by Dme and by the combined activities of phosphoenolpyruvate (PEP)
      carboxykinase (PckA) and pyruvate kinase (PykA). Both pathways enable N2
      fixation, but the PckA/PykA pathway supports N2 fixation at only 60% of that for
      Dme. Double mutants of dme and pckA/pykA did not fix N2. Furthermore, dme pykA
      double mutants did not grow on dicarboxylates, showing that they are the only
      pathways for the production of pyruvate from dicarboxylates normally expressed.
      PckA is not expressed in alfalfa bacteroids, resulting in an obligate requirement
      for Dme for pyruvate formation and N2 fixation. When PckA was expressed from a
      constitutive nptII promoter in alfalfa dme bacteroids, acetylene was reduced at
      30% of the wild-type rate, although this level was insufficient to prevent
      nitrogen starvation. Dme has N-terminal, malic enzyme (Me), and C-terminal
      phosphotransacetylase (Pta) domains. Deleting the Pta domain increased the peak
      acetylene reduction rate in 4-week-old pea plants to 140 to 150% of the wild-type
      rate, and this was accompanied by increased nodule mass. Plants infected with Pta
      deletion mutants did not have increased dry weight, demonstrating that there is
      not a sustained change in nitrogen fixation throughout growth. This indicates a
      complex relationship between pyruvate synthesis in bacteroids, nitrogen fixation,
      and plant growth.

PMID- 20675478
TI  - Comparative study of the roles of AhpC and KatE as respiratory antioxidants in
      Brucella abortus 2308.
AB  - Brucella strains are exposed to potentially toxic levels of H2O2 both as a
      consequence of their aerobic metabolism and through the respiratory burst of host
      phagocytes. To evaluate the relative contributions of the sole catalase KatE and
      the peroxiredoxin AhpC produced by these strains in defense against H2O2-mediated
      toxicity, isogenic katE, ahpC, and katE ahpC mutants were constructed and the
      phenotypic properties of these mutants compared with those of the virulent
      parental strain B. abortus 2308. The results of these studies indicate that AhpC
      is the primary detoxifier of endogenous H2O2 generated by aerobic metabolism.
      KatE, on the other hand, plays a major role in scavenging exogenous and
      supraphysiologic levels of H2O2, although this enzyme can play a supporting role
      in the detoxification of H2O2 of endogenous origin if AhpC is absent. B. abortus
      ahpC and katE mutants exhibit wild-type virulence in C57BL/6 and BALB/c mice, but
      the B. abortus ahpC katE double mutant is extremely attenuated, and this
      attenuation is not relieved in derivatives of C57BL/6 mice that lack NADPH
      oxidase (cybb) or inducible nitric oxide synthase (Nos2) activity. These
      experimental findings indicate that the generation of endogenous H2O2 represents
      a relevant environmental stress that B. abortus 2308 must deal with during its
      residence in the host and that AhpC and KatE perform compensatory roles in
      detoxifying this metabolic H2O2.

PMID- 20675479
TI  - Inclusion membrane proteins of Protochlamydia amoebophila UWE25 reveal a
      conserved mechanism for host cell interaction among the Chlamydiae.
AB  - Chlamydiae are a group of obligate intracellular bacteria comprising several
      important human pathogens. Inside the eukaryotic cell, chlamydiae remain within a
      host-derived vesicular compartment, termed the inclusion. They modify the
      inclusion membrane through insertion of unique proteins, which are involved in
      interaction with and manipulation of the host cell. Among chlamydiae, inclusion
      membrane proteins have been exclusively found in members of the family
      Chlamydiaceae, which predominantly infect mammalian and avian hosts. Here, the
      presence of inclusion membrane proteins in Protochlamydia amoebophila UWE25, a
      chlamydial endosymbiont of free-living amoebae, is reported. A genome-wide
      screening for secondary structure motifs resulted in the identification of 23
      putative inclusion membrane proteins for this organism. Immunofluorescence
      analysis demonstrated that five of these proteins were expressed, and four of
      them could be localized to a halo surrounding the intracellular bacteria.
      Colocalization studies showed an almost complete overlap of the signals obtained
      for the four putative inclusion membrane proteins, and immuno-transmission
      electron microscopy unambiguously demonstrated their location in the inclusion
      membrane. The presence of inclusion membrane proteins (designated IncA, IncQ,
      IncR, and IncS) in P. amoebophila shows that this strategy for host cell
      interaction is conserved among the chlamydiae and is used by chlamydial symbionts
      and pathogens alike.

PMID- 20675480
TI  - Different roles of DosS and DosT in the hypoxic adaptation of Mycobacteria.
AB  - The DosS (DevS) and DosT histidine kinases form a two-component system together
      with the DosR (DevR) response regulator in Mycobacterium tuberculosis. DosS and
      DosT, which have high sequence similarity to each other over the length of their
      amino acid sequences, contain two GAF domains (GAF-A and GAF-B) in their N
      terminal sensory domains. Complementation tests in conjunction with phylogenetic
      analysis showed that DevS of Mycobacterium smegmatis is more closely related to
      DosT than DosS. We also demonstrated in vivo that DosS and DosT of M.
      tuberculosis play a differential role in hypoxic adaptation. DosT responds to a
      decrease in oxygen tension more sensitively and strongly than DosS, which might
      be attributable to their different autooxidation rates. The different
      responsiveness of DosS and DosT to hypoxia is due to the difference in their GAF
      A domains accommodating the hemes. Multiple alignment analysis of the GAF-A
      domains of mycobacterial DosS (DosT) homologs and subsequent site-directed
      mutagenesis revealed that just one substitution of E87, D90, H97, L118, or T169
      of DosS with the corresponding residue of DosT is sufficient to convert DosS to
      DosT with regard to the responsiveness to changes in oxygen tension.

PMID- 20675481
TI  - Characterization of the enzymes encoded by the anthrose biosynthetic operon of
      Bacillus anthracis.
AB  - Bacillus anthracis spores, the etiological agents of anthrax, possess a loosely
      fitting outer layer called the exosporium that is composed of a basal layer and
      an external hairlike nap. The filaments of the nap are formed by trimers of the
      collagenlike glycoprotein BclA. Multiple pentasaccharide and trisaccharide side
      chains are O linked to BclA. The nonreducing terminal residue of the
      pentasaccharide side chain is the unusual sugar anthrose. A plausible
      biosynthetic pathway for anthrose biosynthesis has been proposed, and an antABCD
      operon encoding four putative anthrose biosynthetic enzymes has been identified.
      In this study, we genetically and biochemically characterized the activities of
      these enzymes. We also used mutant B. anthracis strains to determine the effects
      on BclA glycosylation of individually inactivating the genes of the anthrose
      operon. The inactivation of antA resulted in the appearance of BclA
      pentasaccharides containing anthrose analogs possessing shorter side chains
      linked to the amino group of the sugar. The inactivation of antB resulted in BclA
      being replaced with only trisaccharides, suggesting that the enzyme encoded by
      the gene is a dTDP-beta-L-rhamnose alpha-1,3-L-rhamnosyl transferase that
      attaches the fourth residue of the pentasaccharide side chain. The inactivation
      of antC and antD resulted in the disappearance of BclA pentasaccharides and the
      appearance of a tetrasaccharide lacking anthrose. These phenotypes are entirely
      consistent with the proposed roles for the antABCD-encoded enzymes in anthrose
      biosynthesis. Purified AntA was then shown to exhibit beta-methylcrotonyl
      coenzyme A (CoA) hydratase activity, as we predicted. Similarly, we confirmed
      that purified AntC had aminotransferase activity and that purified AntD displayed
      N-acyltransferase activity.

PMID- 20675482
TI  - The PpaA/AerR regulators of photosynthesis gene expression from anoxygenic
      phototrophic proteobacteria contain heme-binding SCHIC domains.
AB  - The SCHIC domain of the B12-binding domain family present in the Rhodobacter
      sphaeroides AppA protein binds heme and senses oxygen. Here we show that the
      predicted SCHIC domain PpaA/AerR regulators also bind heme and respond to oxygen
      in vitro, despite their low sequence identity with AppA.

PMID- 20675483
TI  - Catabolic function of compartmentalized alanine dehydrogenase in the heterocyst
      forming cyanobacterium Anabaena sp. strain PCC 7120.
AB  - In the diazotrophic filaments of heterocyst-forming cyanobacteria, an exchange of
      metabolites takes place between vegetative cells and heterocysts that results in
      a net transfer of reduced carbon to the heterocysts and of fixed nitrogen to the
      vegetative cells. Open reading frame alr2355 of the genome of Anabaena sp. strain
      PCC 7120 is the ald gene encoding alanine dehydrogenase. A strain carrying a
      green fluorescent protein (GFP) fusion to the N terminus of Ald (Ald-N-GFP)
      showed that the ald gene is expressed in differentiating and mature heterocysts.
      Inactivation of ald resulted in a lack of alanine dehydrogenase activity, a
      substantially decreased nitrogenase activity, and a 50% reduction in the rate of
      diazotrophic growth. Whereas production of alanine was not affected in the ald
      mutant, in vivo labeling with [14C]alanine (in whole filaments and isolated
      heterocysts) or [14C]pyruvate (in whole filaments) showed that alanine catabolism
      was hampered. Thus, alanine catabolism in the heterocysts is needed for normal
      diazotrophic growth. Our results extend the significance of a previous work that
      suggested that alanine is transported from vegetative cells into heterocysts in
      the diazotrophic Anabaena filament.

PMID- 20675484
TI  - Bathy phytochromes in rhizobial soil bacteria.
AB  - Phytochromes are biliprotein photoreceptors that are found in plants, bacteria,
      and fungi. Prototypical phytochromes have a Pr ground state that absorbs in the
      red spectral range and is converted by light into the Pfr form, which absorbs
      longer-wavelength, far-red light. Recently, some bacterial phytochromes have been
      described that undergo dark conversion of Pr to Pfr and thus have a Pfr ground
      state. We show here that such so-called bathy phytochromes are widely distributed
      among bacteria that belong to the order Rhizobiales. We measured in vivo spectral
      properties and the direction of dark conversion for species which have either one
      or two phytochrome genes. Agrobacterium tumefaciens C58 contains one bathy
      phytochrome and a second phytochrome which undergoes dark conversion of Pfr to Pr
      in vivo. The related species Agrobacterium vitis S4 contains also one bathy
      phytochrome and another phytochrome with novel spectral properties. Rhizobium
      leguminosarum 3841, Rhizobium etli CIAT652, and Azorhizobium caulinodans ORS571
      contain a single phytochrome of the bathy type, whereas Xanthobacter
      autotrophicus Py2 contains a single phytochrome with dark conversion of Pfr to
      Pr. We propose that bathy phytochromes are adaptations to the light regime in the
      soil. Most bacterial phytochromes are light-regulated histidine kinases, some of
      which have a C-terminal response regulator subunit on the same protein. According
      to our phylogenetic studies, the group of phytochromes with this domain
      arrangement has evolved from a bathy phytochrome progenitor.

PMID- 20675485
TI  - Regulation of a novel gene cluster involved in secondary metabolite production in
      Streptomyces coelicolor.
AB  - Antibiotic biosynthesis in the streptomycetes is a complex and highly regulated
      process. Here, we provide evidence for the contribution of a novel genetic locus
      to antibiotic production in Streptomyces coelicolor. The overexpression of a gene
      cluster comprising four protein-encoding genes (abeABCD) and an antisense RNA
      encoding gene (alpha-abeA) stimulated the production of the blue-pigmented
      metabolite actinorhodin on solid medium. Actinorhodin production also was
      enhanced by the overexpression of an adjacent gene (abeR) encoding a predicted
      Streptomyces antibiotic regulatory protein (SARP), while the deletion of this
      gene impaired actinorhodin production. We found the abe genes to be
      differentially regulated and controlled at multiple levels. Upstream of abeA was
      a promoter that directed the transcription of abeABCD at a low but constitutive
      level. The expression of abeBCD was, however, significantly upregulated at a time
      that coincided with the initiation of aerial development and the onset of
      secondary metabolism; this expression was activated by the binding of AbeR to
      four heptameric repeats upstream of a promoter within abeA. Expressed divergently
      to the abeBCD promoter was alpha-abeA, whose expression mirrored that of abeBCD
      but did not require activation by AbeR. Instead, alpha-abeA transcript levels
      were subject to negative control by the double-strand-specific RNase, RNase III.

PMID- 20675486
TI  - Complete genome sequence of Lactobacillus casei Zhang, a new probiotic strain
      isolated from traditional homemade koumiss in Inner Mongolia, China.
AB  - Lactobacillus casei Zhang is a new probiotic bacterium isolated from koumiss
      collected in Inner Mongolia, China. Here, we report the main genome features of
      L. casei Zhang and the identification of several predicted proteins implicated in
      interactions with the host.

PMID- 20675487
TI  - Draft genome sequences of two Neisseria meningitidis serogroup C clinical
      isolates.
AB  - Neisseria meningitidis is a human-specific pathogen known for its capability to
      cause sepsis and meningitis. Here we report the availability of 2 draft genome
      sequences obtained from patients infected during the same epidemic outbreak. Both
      bacterial isolates belong to serogroup C, but their genome sequences show local
      and remarkable differences compared with each other or with the reference genome
      of strain FAM18.

PMID- 20675488
TI  - Complete genome sequence of Lactobacillus salivarius CECT 5713, a probiotic
      strain isolated from human milk and infant feces.
AB  - Lactobacillus salivarius is a homofermentative lactic acid bacterium and is
      frequently isolated from mucosal surfaces of healthy humans. L. salivarius CECT
      5713, a strain isolated simultaneously from breast milk and infant feces of a
      healthy mother-infant pair, has immunomodulatory, anti-inflammatory, and anti
      infectious properties, as revealed by several in vitro and in vivo assays. Here,
      we report its complete and annotated genome sequence.

PMID- 20675489
TI  - The E2 domain of OdhA of Corynebacterium glutamicum has succinyltransferase
      activity dependent on lipoyl residues of the acetyltransferase AceF.
AB  - Oxoglutarate dehydrogenase (ODH) and pyruvate dehydrogenase (PDH) complexes
      catalyze key reactions in central metabolism, and in Corynebacterium glutamicum
      there is indication of an unusual supercomplex consisting of AceE (E1), AceF
      (E2), and Lpd (E3) together with OdhA. OdhA is a fusion protein of additional E1
      and E2 domains, and odhA orthologs are present in all Corynebacterineae,
      including, for instance, Mycobacterium tuberculosis. Here we show that deletion
      of any of the individual domains of OdhA in C. glutamicum resulted in loss of ODH
      activity, whereas PDH was still functional. On the other hand, deletion of AceF
      disabled both PDH activity and ODH activity as well, although isolated AceF
      protein had solely transacetylase activity and no transsuccinylase activity.
      Surprisingly, the isolated OdhA protein was inactive with 2-oxoglutarate as the
      substrate, but it gained transsuccinylase activity upon addition of
      dihydrolipoamide. Further enzymatic analysis of mutant proteins and mutant cells
      revealed that OdhA specifically catalyzes the E1 and E2 reaction to convert 2
      oxoglutarate to succinyl-coenzyme A (CoA) but fully relies on the lipoyl residues
      provided by AceF involved in the reactions to convert pyruvate to acetyl-CoA. It
      therefore appears that in the putative supercomplex in C. glutamicum, in addition
      to dihydrolipoyl dehydrogenase E3, lipoyl domains are also shared, thus
      confirming the unique evolutionary position of bacteria such as C. glutamicum and
      M. tuberculosis.

PMID- 20675490
TI  - Characterization of NADH oxidase/NADPH polysulfide oxidoreductase and its
      unexpected participation in oxygen sensitivity in an anaerobic hyperthermophilic
      archaeon.
AB  - Many genomes of anaerobic hyperthermophiles encode multiple homologs of NAD(P)H
      oxidase that are thought to function in response to oxidative stress. We
      investigated one of the seven NAD(P)H oxidase homologs (TK1481) in the sulfur
      reducing hyperthermophilic archaeon Thermococcus kodakarensis, focusing on the
      catalytic properties and roles in oxidative-stress defense and sulfur-dependent
      energy conservation. The recombinant form of TK1481 exhibited both NAD(P)H
      oxidase and NAD(P)H:polysulfide oxidoreductase activities. The enzyme also
      possessed low NAD(P)H peroxidase and NAD(P)H:elemental sulfur oxidoreductase
      activities under anaerobic conditions. A mutant form of the enzyme, in which the
      putative redox-active residue Cys43 was replaced by Ala, still showed NADH
      dependent flavin adenine dinucleotide (FAD) reduction activity. Although it also
      retained successive oxidase and anaerobic peroxidase activities, the ability to
      reduce polysulfide and sulfur was completely lost, suggesting the specific
      reactivity of the Cys43 residue for sulfur. To evaluate the physiological
      function of TK1481, we constructed a gene deletant, DeltaTK1481, and mutant
      KUTK1481C43A, into which two base mutations altering Cys43 of TK1481 to Ala were
      introduced. DeltaTK1481 exhibited growth properties nearly identical to those of
      the parent strain, KU216, in sulfur-containing media. Interestingly, in the
      absence of elemental sulfur, the growth of DeltaTK1481 was not affected by
      dissolved oxygen, whereas the growth of KU216 and KUTK1481C43A was significantly
      impaired. These results indicate that although TK1481 does not play a critical
      role in either sulfur reduction or the response to oxidative stress, the NAD(P)H
      oxidase activity of TK1481 unexpectedly participates in the oxygen sensitivity of
      the hyperthermophilic archaeon T. kodakarensis in the absence of sulfur.

PMID- 20675491
TI  - A group IIC-type intron interrupts the rRNA methylase gene of Geobacillus
      stearothermophilus strain 10.
AB  - Group IIC introns insert next to the stem-loop structure of rho-independent
      transcription terminators, thus avoiding intact genes. The insertion sites of 17
      copies of the G.st.I1 intron from Geobacillus stearothermophilus were compared.
      One copy of the intron was found to interrupt an open reading frame (ORF)
      encoding an rRNA methylase.

PMID- 20675492
TI  - Inhibiting the initiation of Clostridium difficile spore germination using
      analogs of chenodeoxycholic acid, a bile acid.
AB  - To cause disease, Clostridium difficile spores must germinate in the host
      gastrointestinal tract. Germination is initiated upon exposure to glycine and
      certain bile acids, e.g., taurocholate. Chenodeoxycholate, another bile acid,
      inhibits taurocholate-mediated germination. By applying Michaelis-Menten kinetic
      analysis to C. difficile spore germination, we found that chenodeoxycholate is a
      competitive inhibitor of taurocholate-mediated germination and appears to
      interact with the spores with greater apparent affinity than does taurocholate.
      We also report that several analogs of chenodeoxycholate are even more effective
      inhibitors. Some of these compounds resist 7alpha-dehydroxylation by Clostridium
      scindens, a core member of the normal human colonic microbiota, suggesting that
      they are more stable than chenodeoxycholate in the colonic environment.

PMID- 20675493
TI  - Staphylococcus aureus NrdH redoxin is a reductant of the class Ib ribonucleotide
      reductase.
AB  - Staphylococci contain a class Ib NrdEF ribonucleotide reductase (RNR) that is
      responsible, under aerobic conditions, for the synthesis of deoxyribonucleotide
      precursors for DNA synthesis and repair. The genes encoding that RNR are
      contained in an operon consisting of three genes, nrdIEF, whereas many other
      class Ib RNR operons contain a fourth gene, nrdH, that determines a thiol redoxin
      protein, NrdH. We identified a 77-amino-acid open reading frame in Staphylococcus
      aureus that resembles NrdH proteins. However, S. aureus NrdH differs
      significantly from the canonical NrdH both in its redox-active site, C-P-P-C
      instead of C-M/V-Q-C, and in the absence of the C-terminal [WF]SGFRP[DE]
      structural motif. We show that S. aureus NrdH is a thiol redox protein. It is not
      essential for aerobic or anaerobic growth and appears to have a marginal role in
      protection against oxidative stress. In vitro, S. aureus NrdH was found to be an
      efficient reductant of disulfide bonds in low-molecular-weight substrates and
      proteins using dithiothreitol as the source of reducing power and an effective
      reductant for the homologous class Ib RNR employing thioredoxin reductase and
      NADPH as the source of the reducing power. Its ability to reduce NrdEF is
      comparable to that of thioredoxin-thioredoxin reductase. Hence, S. aureus
      contains two alternative thiol redox proteins, NrdH and thioredoxin, with both
      proteins being able to function in vitro with thioredoxin reductase as the
      immediate hydrogen donors for the class Ib RNR. It remains to be clarified under
      which in vivo physiological conditions the two systems are used.

PMID- 20675494
TI  - Toxicity of the colicin M catalytic domain exported to the periplasm is FkpA
      independent.
AB  - Colicin M (ColM) is a bactericidal protein that kills sensitive cells by
      hydrolyzing lipid II, involved in the biosynthesis of cell wall peptidoglycan. It
      recognizes FhuA on the outer leaflet, and its translocation through the outer
      membrane depends on the energized Ton complex in the inner membrane. To be active
      in the periplasm, ColM must be translocated through the outer membrane and then
      interact with FkpA, a periplasmic protein that exhibits both cis- and trans
      peptidylprolyl isomerase (PPiase) and chaperon activities. In an attempt to
      directly target ColM to the periplasm of the producing bacteria, we fused the
      presequence of OmpA to ColM (sp-ColM). We found that expression of this hybrid
      protein in an Escherichia coli strain devoid of ColM immunity protein (Cmi) was
      bactericidal. We showed that sp-ColM was correctly expressed, processed, and
      associated with the inner membrane. sp-ColM toxicity was related to its enzymatic
      activity and did not rely on the TonB import proteins or the FhuA receptor. The
      presence of both activity domains of FkpA was still required for sp-ColM
      activity. Analyses of deletion mutants of sp-ColM show that the domain required
      for toxicity corresponds to the C-terminal last 153 amino acids of ColM. Like the
      full-length protein, this domain is not active in the presence of the immunity
      protein Cmi. On the other hand, it does not require FkpA for toxic activity.

PMID- 20675495
TI  - Human hypervirulent Clostridium difficile strains exhibit increased sporulation
      as well as robust toxin production.
AB  - Toxigenic Clostridium difficile strains produce two toxins (TcdA and TcdB) during
      the stationary phase of growth and are the leading cause of antibiotic-associated
      diarrhea. C. difficile isolates of the molecular type NAP1/027/BI have been
      associated with severe disease and hospital outbreaks worldwide. It has been
      suggested that these "hypervirulent" strains produce larger amounts of toxin and
      that a mutation in a putative negative regulator (TcdC) allows toxin production
      at all growth phases. To rigorously explore this possibility, we conducted a
      quantitative examination of the toxin production of multiple hypervirulent and
      nonhypervirulent C. difficile strains. Toxin gene (tcdA and tcdB) and toxin gene
      regulator (tcdR and tcdC) expression was also monitored. To obtain additional
      correlates for the hypervirulence phenotype, sporulation kinetics and efficiency
      were measured. In the exponential phase, low basal levels of tcdA, tcdB, and tcdR
      expression were evident in both hypervirulent and nonhypervirulent strains, but
      contrary to previous assumptions, toxin levels were below the detectable
      thresholds. While hypervirulent strains displayed robust toxin production during
      the stationary phase of growth, the amounts were not significantly different from
      those of the nonhypervirulent strains tested; further, total toxin amounts were
      directly proportional to tcdA, tcdB, and tcdR gene expression. Interestingly,
      tcdC expression did not diminish in stationary phase, suggesting that TcdC may
      have a modulatory rather than a strictly repressive role. Comparative genomic
      analyses of the closely related nonhypervirulent strains VPI 10463 (the highest
      toxin producer) and 630 (the lowest toxin producer) revealed polymorphisms in the
      tcdR ribosome binding site and the tcdR-tcdB intergenic region, suggesting that a
      mechanistic basis for increased toxin production in VPI 10463 could be increased
      TcdR translation and read-through transcription of the tcdA and tcdB genes.
      Hypervirulent isolates produced significantly more spores, and did so earlier,
      than all other isolates. Increased sporulation, potentially in synergy with
      robust toxin production, may therefore contribute to the widespread disease now
      associated with hypervirulent C. difficile strains.

PMID- 20675496
TI  - The twin arginine transport system appears to be essential for viability in
      Sinorhizobium meliloti.
AB  - The twin arginine transport (Tat) system is responsible for transporting
      prefolded proteins to the periplasmic space. The Tat pathway has been implicated
      in many bacterial cellular functions, including motility, biofilm formation, and
      pathogenesis and symbiosis. Since the annotation of Sinorhizobium meliloti Rm1021
      genome suggests that there may be up to 94 putative Tat substrates, we
      hypothesized that characterizing the twin arginine transport system in this
      organism might yield unique data that could help in the understanding of twin
      arginine transport. To initiate this work we attempted a targeted mutagenesis of
      the tat locus. Despite repeated attempts using a number of different types of
      media, the attempts at mutation construction were unsuccessful unless the
      experiment was carried out in a strain that was merodiploid for tatABC. In
      addition, it was shown that a plasmid carrying tatABC was stable in the absence
      of antibiotic selection in a tat deletion background. Finally, fluorescence
      microscopy and live/dead assays of these cultures show a high proportion of dead
      and irregularly shaped cells, suggesting that the loss of tatABC is inversely
      correlated with viability. Taken together, the results of this work provide
      evidence that the twin arginine transport system of S. meliloti appears to be
      essential for viability under all the conditions that we had tested.

PMID- 20675497
TI  - Transcriptional profiling of XdrA, a new regulator of spa transcription in
      Staphylococcus aureus.
AB  - Transcription of spa, encoding the virulence factor protein A in Staphylococcus
      aureus, is tightly controlled by a complex regulatory network, ensuring its
      temporal expression over growth and at appropriate stages of the infection
      process. Transcriptomic profiling of XdrA, a DNA-binding protein that is
      conserved in all S. aureus genomes and shares similarity with the XRE family of
      helix-turn-helix, antitoxin-like proteins, revealed it to be a previously
      unidentified activator of spa transcription. To assess how XdrA fits into the
      complex web of spa regulation, a series of regulatory mutants were constructed;
      consisting of single, double, triple, and quadruple mutants lacking XdrA and/or
      the three key regulators previously shown to influence spa transcription directly
      (SarS, SarA, and RNAIII). A series of lacZ reporter gene fusions containing
      nested deletions of the spa promoter identified regions influenced by XdrA and
      the other three regulators. XdrA had almost as strong an activating effect on spa
      as SarS and acted on the same spa operator regions as SarS, or closely
      overlapping regions. All data from microarrays, Northern and Western blot
      analyses, and reporter gene fusion experiments indicated that XdrA is a major
      activator of spa expression that appears to act directly on the spa promoter and
      not through previously characterized regulators.

PMID- 20675498
TI  - A NAC for regulating metabolism: the nitrogen assimilation control protein (NAC)
      from Klebsiella pneumoniae.
AB  - The nitrogen assimilation control protein (NAC) is a LysR-type transcriptional
      regulator (LTTR) that is made under conditions of nitrogen-limited growth. NAC's
      synthesis is entirely dependent on phosphorylated NtrC from the two-component Ntr
      system and requires the unusual sigma factor sigma54 for transcription of the nac
      gene. NAC activates the transcription of sigma70-dependent genes whose products
      provide the cell with ammonia or glutamate. NAC represses genes whose products
      use ammonia and also represses its own transcription. In addition, NAC also
      subtly adjusts other cellular functions to keep pace with the supply of
      biosynthetically available nitrogen.

PMID- 20675500
TI  - Paediatric primary care in Europe: variation between countries.

PMID- 20675499
TI  - The genome sequence of the cyanobacterium Oscillatoria sp. PCC 6506 reveals
      several gene clusters responsible for the biosynthesis of toxins and secondary
      metabolites.
AB  - We report a draft sequence of the genome of Oscillatoria sp. PCC 6506, a
      cyanobacterium that produces anatoxin-a and homoanatoxin-a, two neurotoxins, and
      cylindrospermopsin, a cytotoxin. Beside the clusters of genes responsible for the
      biosynthesis of these toxins, we have found other clusters of genes likely
      involved in the biosynthesis of not-yet-identified secondary metabolites.

PMID- 20675501
TI  - Health experiences of adolescents with uncontrolled severe asthma.
AB  - BACKGROUND AND AIMS: Many adolescents with asthma experience continued symptoms
      and impaired quality of life despite modern therapy. This study sought to
      understand their experience and to use this understanding to improve their
      clinical management. DESIGN AND SUBJECTS: Qualitative study based on in-depth
      semi-structured interviews conducted with adolescents with uncontrolled severe
      asthma. RESULTS: 22 adolescents (11-18 years) with uncontrolled severe asthma
      were interviewed. Two of the overarching themes that emerged were: (A) medication
      and adherence; and (B) interaction with healthcare professionals and adherence
      with their advice. Despite frequent visits to clinic, some did not understand why
      they were using medications. Many felt that only some medications worked and were
      concerned about adverse effects. Factors related to intentional non-adherence
      were not being 'bothered' and conflicts with other activities. In particular,
      most were not using their spacer. Some though perceived a positive benefit to
      using their preventer treatment. Half the participants lived with a pet that they
      were sensitised to and two-thirds lived with a smoker. Adolescents felt involved
      in the clinic consultation and felt it was helpful but many did not take
      responsibility for interacting with health professionals. Parents were relied on
      to report symptoms, translate medical terms and remember the management plan.
      CONCLUSIONS: Adherence was often poor particularly with the use of spacers.
      Adolescents had a poor understanding of their medication and using it often
      conflicted with other activities. Adolescents are very reliant on their parents.
      Healthcare professionals need to work to empower them to gradually take on the
      responsibility for their asthma.

PMID- 20675502
TI  - ASN End-Stage Renal Disease Task Force: perspective on prospective payments for
      renal dialysis facilities.

PMID- 20675503
TI  - Single HPV test not useful for predicting CIN2 or worse or for guiding choice of
      further investigations for women aged 20-59 presenting to NHS Cervical Screening
      Programme with borderline abnormalities or mild dyskaryosis.

PMID- 20675504
TI  - In permanent atrial fibrillation, lenient rate control is not inferior to strict
      rate control for preventing cardiovascular morbidity and mortality.

PMID- 20675505
TI  - 40-year-old man with nausea and vomiting "found down".

PMID- 20675506
TI  - Fluorodeoxyglucose-PET/CT for diagnosis of intravascular large B-cell lymphoma.

PMID- 20675507
TI  - Patient-computer dialogue: a hope for the future.

PMID- 20675508
TI  - Characterization of bacterial infections in allogeneic hematopoietic stem cell
      transplant recipients who received prophylactic levofloxacin with either
      penicillin or doxycycline.
AB  - OBJECTIVE: To describe the effect of a combination prophylactic regimen of
      levofloxacin, a synthetic chemotherapeutic antibiotic of the fluoroquinolone drug
      class, with either penicillin or doxycycline on the changing epidemiology of
      bacterial infections and antimicrobial resistance patterns of isolated organisms
      in the allogeneic hematopoietic stem cell transplant (HSCT) patient population.
      PATIENTS AND METHODS: We conducted a single-center, retrospective cohort study of
      all allogeneic HSCT recipients from January 1, 2003, through August 31, 2008, who
      received prophylactic levofloxacin in combination with penicillin (or with
      doxycycline in penicillin-allergic patients) from allogeneic stem cell infusion
      until neutrophil engraftment. RESULTS: Of the 258 patients who underwent
      allogeneic HSCT during the study period, 231 received levofloxacin prophylaxis,
      76 (33%) of whom developed an infection within 3 months after transplant. Over
      time, the ratio of gram-positive to gram-negative (GN) infections decreased from
      2.11 in 2004, the first year that GN organisms were isolated, to 1.11 in 2008
      (P=.20). Emergence of fluoroquinolone-resistant GN bacteria was observed (P=.02),
      whereas resistance to extended-spectrum beta-lactams did not change over time.
      Combined vancomycin-resistant enterococci colonization and infection rates
      increased during the study period (P=.04). Clostridium difficile colitis was
      uncommon. CONCLUSION: Levofloxacin with penicillin or doxycycline prophylaxis may
      contribute to the emergence of resistant GN infections in allogeneic HSCT
      recipients over time. Our findings provide additional support for the current
      standard of practice of administering empiric monotherapy with an antipseudomonal
      beta-lactam if these patients develop fever or are suspected to have an
      infection.

PMID- 20675509
TI  - Flexible endoscopic management of Zenker diverticulum: the Mayo Clinic
      experience.
AB  - OBJECTIVE: To describe the outcome of patients undergoing flexible endoscopic
      therapy for symptomatic Zenker diverticulum. PATIENTS AND METHODS: We
      retrospectively evaluated the outcome of 22 consecutive patients who underwent
      flexible endoscopic cricopharyngeal myotomy using needle-knife electrocautery
      performed by a single endoscopist from March 2006 through January 2010. RESULTS:
      Of the 22 patients with symptomatic Zenker diverticulum, 13 were men and 9 were
      women (median age, 84.5 years). Moderate sedation was used in all but 3 (14%) of
      the patients. Postprocedural free air occurred in 6 patients (27%) and resolved
      uneventfully in all. Another patient developed a neck abscess 1 week after
      endoscopic treatment, which was surgically drained. All procedures were performed
      on an outpatient basis, although 8 patients (36%) required subsequent
      hospitalization. The mean (SD) length of stay in the hospital was 2.9 (1.64)
      days. All patients had initial symptomatic improvement, and 18 (82%) maintained
      improvement at a mean (SD) follow-up of 12.7 (9.2) months. CONCLUSION: Flexible
      endoscopic cricopharyngeal myotomy is an effective treatment of symptomatic
      Zenker diverticulum, with low recurrence rates and with the benefit of no general
      anesthesia and hospitalization in most cases. Esophageal perforation is the most
      common procedural complication.

PMID- 20675510
TI  - The visiting medical student clerkship program at Mayo Clinic.
AB  - OBJECTIVE: To describe the history, objectives, statistics, and initiatives used
      to address challenges associated with the Mayo Clinic Visiting Medical Student
      (VMS) Clerkship Program. MATERIALS AND METHODS: Mayo Clinic administrative
      records were reviewed for calendar years 1995 through 2008 to determine the
      effect of interventions to increase the numbers of appropriately qualified
      international VMSs and underrepresented minority VMSs. For numerical data,
      descriptive statistics were used; for comparisons, chi(2) tests were performed.
      RESULTS: During the specified period, 4908 VMSs participated in the Mayo VMS
      Program (yearly mean [SD], 351 [24]). Most students were from US medical schools
      (3247 [66%]) and were male (3084 [63%]). Overall, 3101 VMSs (63%) applied for and
      935 (30%) were appointed to Mayo Clinic residency program positions.
      Interventions to address the challenge of large numbers of international students
      who participated in our VMS program but did not apply for Mayo residency
      positions resulted in significantly fewer international students participating in
      our VMS program (P<.001), applying for Mayo residency program positions (P<.001),
      and being appointed to residency positions (P=.001). Interventions to address the
      challenge of low numbers of underrepresented minority students resulted in
      significantly more of these students participating in our VMS program (P=.005),
      applying for Mayo residency positions (P=.008), and being appointed to residency
      positions (P=.04). CONCLUSION: Our findings suggest that specific interventions
      can affect the characteristics of students who participate in VMS programs and
      who apply for and are appointed to residency program positions.

PMID- 20675511
TI  - Resident physicians' knowledge of underserved patients: a multi-institutional
      survey.
AB  - OBJECTIVE: To measure actual and perceived resident physician knowledge of
      underserved patient populations. PARTICIPANTS AND METHODS: Using the existing
      literature on vulnerable patient populations and interviews with experts in the
      field, we designed a cross-sectional, multi-institutional survey to assess actual
      and perceived resident knowledge of topics related to underserved populations.
      The survey of actual knowledge consisted of 30 multiple-choice questions, and the
      survey of perceived knowledge consisted of 15 items based on 3-point Likert
      scales of confidence. RESULTS: A total of 498 surveys were completed at 18
      residency programs representing 7 different specialties at 10 US institutions.
      Assessment of perceived knowledge demonstrated that residents were very confident
      only 14.0% of the time, somewhat confident 66.4% of the time, and not at all
      confident 19.6% of the time. Assessment of actual knowledge revealed that the
      average percent correct across all 30 questions was 38%. Women scored better than
      men (average score, 40.6% vs 36.0%; P=.01), and African Americans scored higher
      than members of other racial or ethnic groups (average score, 43.5% vs 38.0%;
      P=.04). Associations between residents' perceived and actual knowledge were
      generally high. CONCLUSION: For the US residents surveyed, the actual and
      perceived knowledge about most topics relating to underserved populations was
      low, whereas associations between actual and perceived knowledge were high. These
      findings suggest the need to improve resident education regarding underserved
      patient populations.

PMID- 20675512
TI  - Eight years of the Mayo International Health Program: what an international
      elective adds to resident education.
AB  - OBJECTIVE: To examine the educational benefits of international elective
      rotations during graduate medical education. PARTICIPANTS AND METHODS: We studied
      Mayo International Health Program (MIHP) participants from April 1, 2001, through
      July 31, 2008. Data from the 162 resident postrotation reports were reviewed and
      used to quantitatively and qualitatively analyze MIHP elective experiences.
      Qualitative analysis of the narrative data was performed using NVivo7 (QRS
      International, Melbourne, Australia), a qualitative research program, and
      passages were coded and analyzed for trends and themes. RESULTS: During the study
      period, 162 residents representing 20 different specialties were awarded
      scholarships through the MIHP. Residents rotated in 43 countries, serving over
      40,000 patients worldwide. Their reports indicated multiple educational and
      personal benefits, including gaining experience with a wide variety of pathology,
      learning to work with limited resources, developing clinical and surgical skills,
      participating in resident education, and experiencing new peoples and cultures.
      CONCLUSION: The MIHP provides the structure and funding to enable residents from
      a variety of specialties to participate in international electives and obtain an
      identifiable set of unique, valuable educational experiences likely to shape them
      into better physicians. Such international health electives should be encouraged
      in graduate medical education.

PMID- 20675513
TI  - Vitamin D deficiency in adults: when to test and how to treat.
AB  - Recent evidence for the nonskeletal effects of vitamin D, coupled with
      recognition that vitamin D deficiency is common, has revived interest in this
      hormone. Vitamin D is produced by skin exposed to ultraviolet B radiation or
      obtained from dietary sources, including supplements. Persons commonly at risk
      for vitamin D deficiency include those with inadequate sun exposure, limited oral
      intake, or impaired intestinal absorption. Vitamin D adequacy is best determined
      by measurement of the 25-hydroxyvitamin D concentration in the blood. Average
      daily vitamin D intake in the population at large and current dietary reference
      intake values are often inadequate to maintain optimal vitamin D levels.
      Clinicians may recommend supplementation but be unsure how to choose the optimal
      dose and type of vitamin D and how to use testing to monitor therapy. This review
      outlines strategies to prevent, diagnose, and treat vitamin D deficiency in
      adults.

PMID- 20675514
TI  - 52-year-old woman with dysphagia.

PMID- 20675515
TI  - Incomparable effectiveness--apples to apples?

PMID- 20675516
TI  - Can aquaporin-1 and adipophilin in urine distinguish between malignant and
      nonmalignant renal lesions?

PMID- 20675517
TI  - Using apolipoprotein B to manage dyslipidemia.

PMID- 20675518
TI  - Acute mesenteric ischemia.

PMID- 20675519
TI  - Management of drooling in children.
AB  - Drooling beyond the age of 4 years is neurodevelopmentally abnormal. Chronic
      "sialorrhoea" is seen in children with abnormal oral sensation and/or motor
      control and more infrequently when there is excessive production of saliva.
      Salivary production from the paired glands is under autonomic parasympathetic
      control. Management of the problem relies on multidisciplinary teams with a focus
      on assessment and when appropriate conservative interventions, oral motor
      training, dental appliances, medical and surgical treatment programs. Medically,
      the focus is on modifying the neuroglandular control of saliva with the use of
      anticholinergic agents. The article covers these areas of background, assessment
      and management in detail.

PMID- 20675520
TI  - Intensive insulin therapy-reduced mortality in patients in paediatric intensive
      care.

PMID- 20675521
TI  - The use of inhaled corticosteroids in the wheezy under 5-year-old child.
AB  - Inhaled corticosteroids are established as the most effective long-term anti
      inflammatory therapy for asthma. National and international treatment guidelines
      recommend the use of these agents for long-term asthma control in children. In
      children <5 years, there are significant difficulties in diagnosing asthma. There
      are multiple non-asthma causes of wheeze, and there remains a lack of consensus
      in the description of wheezing phenotypes in this group of children. There is
      also a relative paucity of data concerning the short- and long-term effectiveness
      and side-effects in the under-fives: treatment recommendations have drawn heavily
      from experience of asthma treatment in school-age children and remains
      controversial. This article discusses the important recent advances in the
      evidence-base and current expert opinions which are helping to delineate improved
      outcomes for young children with wheeze.

PMID- 20675522
TI  - Sedation for radiological imaging.

PMID- 20675523
TI  - An all-consuming case.
AB  - This is a case of a 6-month-old child who presented to the local paediatric
      department with a relatively short history of developmental regression,
      hypotonia, weight loss, irritability and hepatosplenomegaly. The child then
      proceeded to spike temperatures up to 39 degrees C. The case demonstrates the
      logical investigative process involved in such a case and discusses the
      differential diagnoses at each stage. It also highlights the importance of multi
      specialty work in complex cases and the potential consequence of premature
      closure of diagnosis.

PMID- 20675524
TI  - Common menstrual problems in adolescence.
AB  - Many girls tell their general practitioners and paediatricians about problems
      with their periods. This article focuses on a practical approach to managing
      menorrhagia, dysmenorrhoea, oligomenorrhoea and premenstrual syndrome (PMS) and
      reviews the literature on this topic.

PMID- 20675525
TI  - Using ePortfolios to support clinical training in paediatrics.

PMID- 20675526
TI  - Drug therapy for chronic asthma in children.
AB  - Asthma is a common chronic illness in children and a successful symptom control
      improves quality of life. Guidelines for the use of drugs in its management are
      widely available, but for children are often based on consensus opinion and
      extrapolation of data from studies in adolescents and adults. The aim of this
      review is to describe the clinical pharmacology of the drugs commonly used to
      manage chronic asthma in children and identify areas where further study might be
      useful to determine their best use.

PMID- 20675535
TI  - The cytoskeleton enhances gene expression in the response to the Harpin elicitor
      in grapevine.
AB  - The cytoskeleton undergoes dramatic reorganization during plant defence. This
      response is generally interpreted as part of the cellular repolarization
      establishing physical barriers against the invading pathogen. To gain insight
      into the functional significance of cytoskeletal responses for defence, two Vitis
      cell cultures that differ in their microtubular dynamics were used, and the
      cytoskeletal response to the elicitor Harpin in parallel to alkalinization of the
      medium as a fast response, and the activation of defence-related genes were
      followed. In one cell line derived from the grapevine cultivar 'Pinot Noir',
      microtubules contained mostly tyrosinylated alpha-tubulin, indicating high
      microtubular turnover, whereas in another cell line derived from the wild
      grapevine V. rupestris, the alpha-tubulin was strongly detyrosinated, indicating
      low microtubular turnover. The cortical microtubules were disrupted and actin
      filaments were bundled in both cell lines, but the responses were elevated in V.
      rupestris as compared with V. vinifera cv. 'Pinot Noir'. The cytoskeletal
      responsiveness correlated with elicitor-induced alkalinization and the expression
      of defence genes. Using resveratrol synthase and stilbene synthase as examples,
      it could be shown that pharmacological manipulation of microtubules could induce
      gene expression in the absence of elicitor. These findings are discussed with
      respect to a role for microtubules as positive regulators of defence-induced gene
      expression.

PMID- 20675536
TI  - Conversations between carers and people with schizophrenia: a qualitative
      analysis using leximancer.
AB  - We examined conversations between people with schizophrenia (PwS) and family or
      professional carers with whom they interacted frequently. We allocated PwS to one
      of two communication profiles: Low-activity communicators talked much less than
      their conversational partners, whereas high-activity communicators talked much
      more. We used Leximancer text analytics software to analyze the conversations. We
      found that carers used different strategies to accommodate to the PwS's behavior,
      depending on the PwS's communication profile and their relationship. These
      findings indicate that optimal communication strategies depend on the PwS's
      conversational tendencies and the relationship context. They also suggest new
      opportunities for qualitative assessment via intelligent text analytics
      technologies.

PMID- 20675537
TI  - Using institutional ethnography to understand the production of health care
      disparities.
AB  - Questions of health care access and equity are often examined by researchers
      using quantitative approaches, describing patterns of service utilization.
      Articles based on such approaches often reveal relatively little about how health
      care services and resources come to be distributed as they are. Articles about
      qualitative research with marginalized people, although offering textured
      accounts of people's experiences of care, often do not systematically link felt
      troubles to specific features of health systems. Institutional ethnography, a
      method of inquiry developed over the past 25 years by Canadian sociologist
      Dorothy Smith and her colleagues, offers a useful resource for researchers
      exploring and addressing health care disparities. Drawing on previous research
      and a study in progress on cancer care in Ontario, Canada, I consider the
      potential of institutional ethnography to make visible how disparities are
      produced in the routine operation of health services.

PMID- 20675538
TI  - Antihypertensive medication adherence among elderly Chinese Americans.
AB  - This study explored the level of antihypertensive medication adherence and
      examined certain demographic attributes and influential factors in relation to
      antihypertensive medication nonadherence among Chinese American elders using a
      descriptive cross-sectional survey design. Findings revealed that 52% of the
      elderly Chinese Americans adhered to their antihypertensive medications. Gender,
      education, years of residency in the United States, years of diagnosed
      hypertension, and perceived safety of taking antihypertensive medications did not
      contribute to the differences in medication adherence. Forgetfulness, medication
      adverse effects, language difficulties, and cultural barriers were the
      influential factors that hinder antihypertensive medication adherence. Developing
      effective and culturally appropriate strategies for Chinese American elders is
      recommended.

PMID- 20675539
TI  - Myoglobin's old and new clothes: from molecular structure to integrated function
      and evolution.

PMID- 20675541
TI  - Keeping the heart in balance: the functional interactions of myoglobin with
      nitrogen oxides.
AB  - Myoglobin (Mb) is an important intracellular oxygen-binding hemoprotein found in
      the cytoplasm of skeletal and cardiac muscle tissue playing a well-known role in
      O(2) storage and delivery. Within the last decade the knowledge about Mb's
      function has been considerably extended by the generation of myoglobin-deficient
      (myo(-/-)) mice, which for the first time enabled the analysis of Mb's role in
      physiology without pharmacological intervention. Utilizing the myo(-/-) mice, it
      has been demonstrated that beyond its function in O(2) supply Mb substantially
      contributes to nitric oxide (NO) homeostasis in the heart. By a dynamic cycle, in
      which a decrease in tissue O(2) tension drives the conversion of Mb from being a
      NO scavenger under normoxia to a NO producer during hypoxia, mitochondrial
      respiration is reversibly adapted to the intracellular O(2) tension. Therefore,
      Mb may act as an important O(2) sensor through which NO can regulate muscle
      energetics and function. As Mb is widespread throughout the fauna, the diverse
      oxygen-dependent interactions between Mb and nitrogen oxides may not only be of
      relevance for mammals but also for other vertebrates as evidenced by comparable
      phenotypes of 'artificial' (myo(-/-) mice) and 'natural' Mb knockouts (icefish
      and amphibians). In conclusion, it seems likely that Mb's multifunctional
      properties create an environment characterized by a tightly adapted aerobic
      mitochondrial respiration and low levels of free radicals, and thus serve an
      essential and beneficial role within the myocardium, which appears to be
      functionally important over a wide range of species.

PMID- 20675540
TI  - Myoglobin's old and new clothes: from molecular structure to function in living
      cells.
AB  - Myoglobin, a mobile carrier of oxygen, is without a doubt an important player
      central to the physiological function of heart and skeletal muscle. Recently,
      researchers have surmounted technical challenges to measure Mb diffusion in the
      living cell. Their observations have stimulated a discussion about the relative
      contribution made by Mb-facilitated diffusion to the total oxygen flux. The
      calculation of the relative contribution, however, depends upon assumptions, the
      cell model and cell architecture, cell bioenergetics, oxygen supply and demand.
      The analysis suggests that important differences can be observed whether steady
      state or transient conditions are considered. This article reviews the current
      evidence underlying the evaluation of the biophysical parameters of myoglobin
      facilitated oxygen diffusion in cells, specifically the intracellular
      concentration of myoglobin, the intracellular diffusion coefficient of myoglobin
      and the intracellular myoglobin oxygen saturation. The review considers the role
      of myoglobin in oxygen transport in vertebrate heart and skeletal muscle, in the
      diving seal during apnea as well as the role of the analogous leghemoglobin of
      plants. The possible role of myoglobin in intracellular fatty acid transport is
      addressed. Finally, the recent measurements of myoglobin diffusion inside muscle
      cells are discussed in terms of their implications for cytoarchitecture and
      microviscosity in these cells and the identification of intracellular impediments
      to the diffusion of proteins inside cells. The recent experimental data then help
      to refine our understanding of Mb function and establish a basis for future
      investigation.

PMID- 20675542
TI  - Unmasking the Janus face of myoglobin in health and disease.
AB  - For more than 100 years, myoglobin has been among the most extensively studied
      proteins. Since the first comprehensive review on myoglobin function as a
      dioxygen store by Millikan in 1939 and the discovery of its structure 50 years
      ago, multiple studies have extended our understanding of its occurrence,
      properties and functions. Beyond the two major roles, the storage and the
      facilitation of dioxygen diffusion, recent physiological studies have revealed
      that myoglobin acts as a potent scavenger of nitric oxide (NO(*)) representing a
      control system that preserves mitochondrial respiration. In addition, myoglobin
      may also protect the heart against reactive oxygen species (ROS), and, under
      hypoxic conditions, deoxygenated myoglobin is able to reduce nitrite to NO(*)
      leading to a downregulation of the cardiac energy status and to a decreased heart
      injury after reoxygenation. Thus, by controlling the NO(*) bioavailability via
      scavenging or formation, myoglobin serves as part of a sensitive dioxygen sensory
      system. In this review, the physiological relevance of these recent findings are
      delineated for pathological states where NO(*) and ROS bioavailability are known
      to be critical determinants for the outcome of the disease, e.g.
      ischemia/reperfusion injury. Detrimental and beneficial effects of the presence
      of myoglobin are discussed for various states of tissue oxygen tension within the
      heart and skeletal muscle. Furthermore, the impact of myoglobin on parasite
      infection, rhabdomyolysis, hindlimb and liver ischemia, angiogenesis and tumor
      growth are considered.

PMID- 20675544
TI  - 'It's hollow': the function of pores within myoglobin.
AB  - Despite a century of research, the cellular function of myoglobin (Mb), the
      mechanism regulating oxygen (O(2)) transport in the cell and the structure
      function relationship of Mb remain incompletely understood. In particular, the
      presence and function of pores within Mb have attracted much recent attention.
      These pores can bind to Xe as well as to other ligands. Indeed, recent cryogenic
      X-ray crystallographic studies using novel techniques have captured snapshots of
      carbon monoxide (CO) migrating through these pores. The observed movement of the
      CO molecule from the heme iron site to the internal cavities and the associated
      structural changes of the amino acid residues around the cavities confirm the
      integral role of the pores in forming a ligand migration pathway from the protein
      surface to the heme. These observations resolve a long-standing controversy - but
      how these pores affect the physiological function of Mb poses a striking question
      at the frontier of biology.

PMID- 20675543
TI  - Regulation of myoglobin expression.
AB  - Myoglobin is a well-characterized, cytoplasmic hemoprotein that is expressed
      primarily in cardiomyocytes and oxidative skeletal muscle fibers. However, recent
      studies also suggest low-level myoglobin expression in various non-muscle
      tissues. Prior studies incorporating molecular, pharmacological, physiological
      and transgenic technologies have demonstrated that myoglobin is an essential
      oxygen-storage hemoprotein capable of facilitating oxygen transport and
      modulating nitric oxide homeostasis within cardiac and skeletal myocytes.
      Concomitant with these studies, scientific investigations into the
      transcriptional regulation of myoglobin expression have been undertaken. These
      studies have indicated that activation of key transcription factors (MEF2, NFAT
      and Sp1) and co-activators (PGC-1alpha) by locomotor activity, differential
      intracellular calcium fluxes and low intracellular oxygen tension collectively
      regulate myoglobin expression. Future studies focused on tissue-specific
      transcriptional regulatory pathways and post-translational modifications
      governing myoglobin expression will need to be undertaken. Finally, further
      studies investigating the modulation of myoglobin expression under various
      myopathic processes may identify myoglobin as a novel therapeutic target for the
      treatment of various cardiac and skeletal myopathies.

PMID- 20675545
TI  - Roles of nitric oxide, nitrite and myoglobin on myocardial efficiency in trout
      (Oncorhynchus mykiss) and goldfish (Carassius auratus): implications for hypoxia
      tolerance.
AB  - The roles of nitric oxide synthase activity (NOS), nitrite and myoglobin (Mb) in
      the regulation of myocardial function during hypoxia were examined in trout and
      goldfish, a hypoxia-intolerant and hypoxia-tolerant species, respectively. We
      measured the effect of NOS inhibition, adrenaline and nitrite on the O(2)
      consumption rate and isometric twitch force development in electrically paced
      ventricular preparations during hypoxia, and measured O(2) affinity and nitrite
      reductase activity of the purified heart Mbs of both species. Upon hypoxia (9%
      O(2)), O(2) consumption and developed force decreased in both trout and goldfish
      myocardium, with trout showing a significant increase in the O(2) utilization
      efficiency, i.e. the ratio of twitch force to O(2) consumption, suggesting an
      increased anaerobic metabolism. NOS inhibition enhanced myocardial O(2)
      consumption and decreased efficiency, indicating that mitochondrial respiration
      is under a tone of NOS-produced NO. When trout myocardial twitch force and O(2)
      consumption are enhanced by adrenaline, this NO tone disappears. Consistent with
      its conversion to NO, nitrite reduced O(2) consumption and increased myocardial
      efficiency in trout but not in goldfish. Such a difference correlates with the
      lower O(2) affinity measured for trout Mb that would increase the fraction of
      deoxygenated heme available to catalyze the reduction of nitrite to NO. Whereas
      low-affinity trout Mb would favor O(2) diffusion within cardiomyocytes at high in
      vivo O(2) tensions, goldfish Mb having higher O(2) affinity and higher nitrite
      reductase activity appears better suited to facilitate O(2) diffusion and nitrite
      reduction in the heart during severe hypoxia, a condition particularly well
      tolerated by this species.

PMID- 20675546
TI  - Repeated bouts of dehydration deplete nutrient reserves and reduce egg production
      in the mosquito Culex pipiens.
AB  - In this study of the mosquito, Culex pipiens, we examined the impact of multiple
      bouts of dehydration and rehydration on survival, depletion of metabolic reserves
      and egg production in both non-diapausing and diapausing females. Mosquitoes
      provided with access to sugar during rehydration survived longer than those
      allowed to rehydrate without sugar, and their survival was similar to that of
      mosquitoes of the same age that were not dehydrated. Among mosquitoes not
      provided with sugar, each dehydration bout reduced the mosquito's dry mass - an
      effect likely to be due to the utilization of carbohydrates and lipid reserves.
      The toll on glycogen and lipid reserves is likely to be especially costly for
      diapausing mosquitoes that are dependent on these stored reserves for winter
      survival. Egg production in both non-diapausing and post-diapausing C. pipiens
      was also reduced in response to multiple bouts of dehydration. Although egg
      quality was not compromised, the number of eggs produced was reduced. Both non
      diapausing and diapausing females can compensate for the nutrient loss due to
      dehydration by sugar feeding but the opportunity to feed on sugar is likely to be
      rarely available in the overwintering habitat of diapausing females, thus the
      impact of dehydration may be especially pronounced in overwintering populations
      of C. pipiens.

PMID- 20675547
TI  - The mechanical power output of the pectoralis muscle of cockatiel (Nymphicus
      hollandicus): the in vivo muscle length trajectory and activity patterns and
      their implications for power modulation.
AB  - In order to meet the varying demands of flight, pectoralis muscle power output
      must be modulated. In birds with pectoralis muscles with a homogeneous fibre type
      composition, power output can be modulated at the level of the motor unit (via
      changes in muscle length trajectory and the pattern of activation), at the level
      of the muscle (via changes in the number of motor units recruited), and at the
      level of the whole animal (through the use of intermittent flight). Pectoralis
      muscle length trajectory and activity patterns were measured in vivo in the
      cockatiel (Nymphicus hollandicus) at a range of flight speeds (0-16 m s(-1))
      using sonomicrometry and electromyography. The work loop technique was used to
      measure the mechanical power output of a bundle of fascicles isolated from the
      pectoralis muscle during simulated in vivo length change and activity patterns.
      The mechanical power-speed relationship was U-shaped, with a 2.97-fold variation
      in power output (40-120 W kg(-1)). In this species, modulation of neuromuscular
      activation is the primary strategy utilised to modulate pectoralis muscle power
      output. Maximum in vivo power output was 22% of the maximum isotonic power output
      (533 W kg(-1)) and was generated at a lower relative shortening velocity (0.28
      V(max)) than the maximum power output during isotonic contractions (0.34 V(max)).
      It seems probable that the large pectoralis muscle strains result in a shift in
      the optimal relative shortening velocity in comparison with the optimum during
      isotonic contractions as a result of length-force effects.

PMID- 20675548
TI  - Comparison between mechanical power requirements of flight estimated using an
      aerodynamic model and in vitro muscle performance in the cockatiel (Nymphicus
      hollandicus).
AB  - There have been few comparisons between the relationship between the mechanical
      power requirements of flight and flight speed obtained using different
      approaches. It is unclear whether differences in the power-speed relationships
      reported in the literature are due to the use of different techniques for
      determining flight power or due to inter-specific differences. Here we compare
      the power-speed relationships in cockatiels (Nymphicus hollandicus) determined
      using both an aerodynamic model and measurements of in vitro performance of
      bundles of pectoralis muscle fibres under simulated in vivo strain and activity
      patterns. Aerodynamic power was calculated using different ranges of values for
      the coefficients in the equations: induced power factor (k 1.0-1.4), the profile
      (C(D, pro) 0.01-0.03) and parasite drag (C(D, par) 0.05-0.195) coefficients. We
      found that the aerodynamic power-speed relationship was highly sensitive to the
      values assumed for these coefficients and best fit the power calculated from in
      vitro muscle performance when k=1.2, C(D, pro)=0.02 and C(D, par)=0.13.

PMID- 20675549
TI  - The metabolic power requirements of flight and estimations of flight muscle
      efficiency in the cockatiel (Nymphicus hollandicus).
AB  - Little is known about how in vivo muscle efficiency, that is the ratio of
      mechanical and metabolic power, is affected by changes in locomotory tasks. One
      of the main problems with determining in vivo muscle efficiency is the large
      number of muscles generally used to produce mechanical power. Animal flight
      provides a unique model for determining muscle efficiency because only one
      muscle, the pectoralis muscle, produces nearly all of the mechanical power
      required for flight. In order to estimate in vivo flight muscle efficiency, we
      measured the metabolic cost of flight across a range of flight speeds (6-13 m s(
      1)) using masked respirometry in the cockatiel (Nymphicus hollandicus) and
      compared it with measurements of mechanical power determined in the same wind
      tunnel. Similar to measurements of the mechanical power-speed relationship, the
      metabolic power-speed relationship had a U-shape, with a minimum at 10 m s(-1).
      Although the mechanical and metabolic power-speed relationships had similar
      minimum power speeds, the metabolic power requirements are not a simple multiple
      of the mechanical power requirements across a range of flight speeds. The
      pectoralis muscle efficiency (estimated from mechanical and metabolic power,
      basal metabolism and an assumed value for the 'postural costs' of flight)
      increased with flight speed and ranged from 6.9% to 11.2%. However, it is
      probable that previous estimates of the postural costs of flight have been too
      low and that the pectoralis muscle efficiency is higher.

PMID- 20675550
TI  - Hypercarbic cardiorespiratory reflexes in the facultative air-breathing fish jeju
      (Hoplerythrinus unitaeniatus): the role of branchial CO2 chemoreceptors.
AB  - The aim of the present study was to determine the roles that externally versus
      internally oriented CO(2)/H(+)-sensitive chemoreceptors might play in promoting
      cardiorespiratory responses to environmental hypercarbia in the air-breathing
      fish, Hoplerythrinus unitaeniatus (jeju). Fish were exposed to graded hypercarbia
      (1, 2.5, 5, 10 and 20% CO(2)) and also to graded levels of environmental acidosis
      (pH approximately 7.0, 6.0, 5.8, 5.6, 5.3 and 4.7) equal to the pH levels of the
      hypercarbic water to distinguish the relative roles of CO(2) versus H(+). We also
      injected boluses of CO(2)-equilibrated solutions (5, 10 and 20% CO(2)) and acid
      solutions equilibrated to the same pH as the CO(2) boluses into the caudal vein
      (internal) and buccal cavity (external) to distinguish between internal and
      external stimuli. The putative location of the chemoreceptors was determined by
      bilateral denervation of branches of cranial nerves IX (glossopharyngeal) and X
      (vagus) to the gills. The data indicate that the chemoreceptors eliciting
      bradycardia, hypertension and gill ventilatory responses (increased frequency and
      amplitude) to hypercarbia are exclusively branchial, externally oriented and
      respond specifically to changes in CO(2) and not H(+). Those involved in
      producing the cardiovascular responses appeared to be distributed across all gill
      arches while those involved in the gill ventilatory responses were located
      primarily on the first gill arch. Higher levels of aquatic CO(2) depressed gill
      ventilation and stimulated air breathing. The chemoreceptors involved in
      producing air breathing in response to hypercarbia also appeared to be branchial,
      distributed across all gill arches and responded specifically to changes in
      aquatic CO(2). This would suggest that chemoreceptor groups with different
      orientations (blood versus water) are involved in eliciting air-breathing
      responses to hypercarbia in jeju.

PMID- 20675551
TI  - Development of a dopaminergic system in sea urchin embryos and larvae.
AB  - The mechanisms that regulate the organized swimming movements of sea urchin
      blastulae are largely unknown. Using immunohistochemistry, we found that dopamine
      (DA) and the Hemicentrotus pulcherrimus homolog of the dopamine receptor D1 (Hp
      DRD1) were strongly co-localized in 1-2 microm diameter granules (DA/DRD1
      granules). Furthermore, these granules were arranged across the entire surface of
      blastulae as they developed locomotory cilia before hatching, and remained
      evident until metamorphosis. DA/DRD1 granules were associated with the basal
      bodies of cilia, and were densely packed in the ciliary band by the eight-arm
      pluteus stage. The transcription of Hp-DRD1 was detected from the unfertilized
      egg stage throughout the period of larval development. Treatment with S-(-)
      carbidopa, an inhibitor of aromatic-l-amino acid decarboxylase, for 20-24 h (i)
      from soon after insemination until the 20 h post-fertilization (20 hpf) early
      gastrula stage and (ii) from the 24 hpf prism larva stage until the 48 hpf
      pluteus stage, inhibited the formation of DA granules and decreased the swimming
      activity of blastulae and larvae in a dose-dependent manner. Exogenous DA rescued
      these deprivations. The formation of DRD1 granules was not affected. However, in
      48 hpf plutei, the serotonergic nervous system (5HT-NS) developed normally.
      Morpholino antisense oligonucleotides directed against Hp-DRD1 inhibited the
      formation of DRD1 granules and the swimming of larvae, but did not disturb the
      formation of DA granules. Thus, the formation of DRD1 granules and DA granules
      occurs chronologically closely but mechanically independently and the swimming of
      blastulae is regulated by the dopaminergic system. In plutei, the 5HT-NS closely
      surrounded the ciliary bands, suggesting the functional collaboration with the
      dopaminergic system in larvae.

PMID- 20675552
TI  - Cuticular plasticization in the tick, Amblyomma hebraeum (Acari: Ixodidae):
      possible roles of monoamines and cuticular pH.
AB  - The degree of plasticization of the alloscutal cuticle of a 'hard' (ixodid) tick,
      Amblyomma hebraeum, and a 'soft' (argasid) tick, Ornithodoros moubata, was
      assessed throughout the blood-feeding period. Cuticle viscosity was calculated
      from rate of creep of cuticle under constant load using a Maxwell model. Feeding
      related plasticization (i.e. increased rate of extension under a constant load)
      occurred in A. hebraeum but not in O. moubata. Maxwell viscosity of unfed A.
      hebraeum cuticle was relatively high (approximately 720 GPa s) but was
      significantly lower in feeding ticks. Small partially fed ticks displayed a
      viscosity of approximately 108 GPa s. Still lower values (42 GPa s) were observed
      in the largest of the engorged ticks. Following cessation of feeding, there was a
      significant but limited reversal in viscosity back to approximately 100 GPa s.
      The water content of cuticle of unfed A. hebraeum (23.4% of wet mass) rose
      sharply after the onset of feeding and reached a plateau value of 34.0% at a
      fed/unfed weight ratio of 3 and beyond. Ixodid ticks lay down new endocuticle
      during the feeding period. The observed increase in cuticle hydration suggests
      that both old and new cuticles are hydrated during feeding. Monoamines may play
      an important role in controlling cuticle viscosity. Dopamine (DA) injected into
      partially fed A. hebraeum caused plasticization. 5-Hydroxytryptamine (serotonin,
      5-HT), which induces plasticization in the blood-sucking insect Rhodnius
      prolixus, had no statistically significant effect on tick cuticle. Octopamine
      (OA) and tyramine both caused cuticle stiffening (i.e. opposed plasticization).
      This suggests a possible inhibitory effect but co-injection of OA with DA did not
      reduce DA-induced plasticization. The mechanism leading to plasticization of tick
      cuticle may involve a change in cuticular pH. The viscosity of tick cuticle loops
      was highest at pH 8.0 (389 GPa s) and fell precipitously in the acidic range to a
      low value of 2.2 GPa s at pH 5.5-5.7. A cuticular pH of approximately 6.5 would
      account for the lowest viscosity observed under physiological conditions (42.4
      GPa s for large, day 0, engorged ticks). The V-ATPase inhibitor, concanamycin A,
      was a potent inhibitor of DA-induced plasticization. These results are consistent
      with a model in which DA acts to cause plasticization through transport of H(+)
      ions into the cuticle. Measurement of cuticular ion (Na(+), K(+), Ca(2+), Mg(2+))
      content did not suggest that plasticization is caused by any of these ions. Taken
      together, our results suggest that the mechanism of cuticular plasticization in
      feeding A. hebraeum is related to hydration, and involves the transport of H(+)
      ions into the sub-cuticular space by cells in the hypodermis. Feeding-induced
      plasticization was not observed in the rapid feeding tick, O. moubata.

PMID- 20675553
TI  - Peak energy turnover in lactating European hares: a test of the heat dissipation
      limitation hypothesis.
AB  - It has been suggested that maximum sustained metabolic rate (SusMR) in mammals as
      reached, for instance, during lactation, is due to a limited capacity for heat
      dissipation. Here, we experimentally tested whether heat dissipation limitation
      (HDL) also constrains energy turnover in lactating European hares.
      Experimentally, we made use of the fact that hares nurse their young only once
      per day, which allowed us to keep females and young either at the same or at
      different ambient temperatures. During the last lactation week (week 4) females
      kept at thermoneutrality (22 degrees C), irrespective of the cold load of their
      young, had significantly lower rates of metabolisable energy intake (MEI) than
      cold-exposed mothers (5 degrees C), as predicted by the HDL hypothesis. However,
      in week 2 of lactation females at thermoneutrality rearing cold-exposed young
      were able to increase MEI to levels indistinguishable from those of cold-exposed
      females. Thus, even at thermoneutral temperature females reached maximum rates of
      energy turnover, which was inconsistent with the HDL hypothesis. We conclude that
      SusMR in lactating European hares typically results not from physiological
      constraints but from an active restriction of their energy turnover in order to
      maximise lifetime reproductive success.

PMID- 20675554
TI  - Sound transmission and the recognition of temporally degraded sexual
      advertisement signals in Cope's gray treefrog (Hyla chrysoscelis).
AB  - Acoustic communication signals degrade as they propagate between signalers and
      receivers. While we generally understand the degrading effects of sound
      propagation on the structure of acoustic signals, we know considerably less about
      how receivers make behavioral decisions based on the perception of degraded
      signals in sonically and structurally complex habitats where communication
      occurs. In this study of acoustic mate recognition in Cope's gray treefrog, Hyla
      chrysoscelis (Cope 1880), we investigated how the temporal structure of male
      advertisement calls was compromised by propagation in a natural habitat and how
      females responded to stimuli mimicking various levels of temporal degradation. In
      a sound transmission experiment, we quantified changes in the pulsed structure of
      signals by broadcasting synthetic calls during active choruses from positions
      where we typically encountered signalers, and re-recording the signals from
      positions where we typically encountered potential receivers. Our main finding
      was that the silent gaps between pulses become increasingly 'filled in' by
      background noise and reverberations as a function of increasing propagation
      distance. We also conducted female phonotaxis experiments to determine the
      threshold modulation depth required to elicit recognition of the pulsatile
      structure of the call. Females were surprisingly tolerant of degraded temporal
      structure, and there was a tendency for greater permissiveness at lower playback
      levels. We discuss these results in terms of presumed mechanisms of call
      recognition in complex environments and the acoustic adaptation hypothesis.

PMID- 20675555
TI  - Electrolytic lesions within central complex neuropils of the cockroach brain
      affect negotiation of barriers.
AB  - Animals must negotiate obstacles in their path in order to successfully function
      within natural environments. These actions require transitions from walking to
      other behaviors, many of which are more involved than simple reflexes. For these
      behaviors to be successful, insects must evaluate objects in their path and then
      use that information to change posture or re-direct leg movements. Some of this
      control may occur within a region of the brain known as the central complex (CC).
      We used discrete electrolytic lesions to examine the role of certain sub-regions
      of the CC in various obstacle negotiation behaviors. We found that cockroaches
      with lesions to the protocerebral bridge (PB) and ellipsoid body (EB) exhibit
      abnormalities in turning and dealing with shelf-like objects; whereas,
      individuals with lesions to the fan-shaped body (FB) and lateral accessory lobe
      (LAL), exhibit abnormalities of those behaviors as well as climbing over blocks
      and up walls to a horizontal plane. Abnormalities in block climbing include
      decreased success rate, changes in climbing strategy, and delayed response to the
      block. Increases in these abnormal behaviors were significant in individuals with
      lesions to the FB and LAL. Although turning abnormalities are present in
      individuals with lesions to the LAL, EB and the lateral region of the FB, there
      are some differences in how these deficits present. For instance, the turning
      deficits seen in individuals with lateral FB lesions only occurred when turning
      in the direction opposite to the side of the brain on which the lesion occurred.
      By contrast, individuals with lesions to the EB and LAL exhibited turning
      abnormalities in both directions. Lesions in the medial region of the FB did not
      result in directional turning deficits, but in abnormalities in block climbing.

PMID- 20675556
TI  - Phenylhydrazine-induced anemia causes nitric-oxide-mediated upregulation of the
      angiogenic pathway in Notothenia coriiceps.
AB  - Antarctic icefishes possess several cardiovascular characteristics that enable
      them to deliver oxygen adequately in the absence of hemoglobin (Hb). To gain
      insight into mechanisms driving development of these cardiovascular
      characteristics of icefish, we chemically induced severe anemia in a red-blooded
      notothenioid, Notothenia coriiceps. After 10 days of treatment with
      phenylhydrazine HCl, the hematocrit and Hb concentration of N. coriiceps
      decreased by >90% and >70%, respectively. Anemic fish exhibited a significantly
      higher concentration of nitric oxide (NO) metabolites in their plasma compared
      with that of control animals, indicating that corporeal levels of NO are higher
      in anemic animals than in control fish. The activity of nitric oxide synthase
      (NOS) was measured in brain, retina, pectoral muscle and ventricle of control and
      anemic animals. With the exception of retina, no significant differences in NOS
      activities were observed, indicating that the increase in plasma NO metabolites
      is due to loss of Hb, which normally plays a major role in the degradation of NO,
      and not due to an overall increase in the capacity for NO production. To
      determine whether loss of Hb can stimulate remodeling of the cardiovascular
      system, we measured expression of HIF-1alpha, PHD2 and VEGF mRNA in retinae of
      control and anemic fish. Expression of all three genes was higher in anemic
      animals compared with control N. coriiceps, suggesting a causative relationship
      between loss of Hb and induction of angiogenesis that probably is mediated
      through nitric oxide signaling.

PMID- 20675557
TI  - Scaling for stress similarity and distorted-shape similarity in bending and
      torsion under maximal muscle forces concurs with geometric similarity among
      different-sized animals.
AB  - When geometric similarity, or isometry, prevails among animals of different sizes
      their form and proportions are similar. Weight increases as the cube of the
      length dimension, while cross-sectional areas increase as its square, so in load
      bearing structural elements the stress, caused by the body weight, increases in
      direct proportion to the length dimension, both for pure axial loads and for
      transverse bending and torsional loads. On this account, large body sizes would
      be expected to set up compensatory selection on the proportions of supporting
      structures, making them disproportionately thicker as required to maintain
      similar, size-independent safety factors against breakage. Most previous scaling
      theories have assumed that the strength of support elements has evolved with
      respect to loads due to the body weight. But then, from the arguments above, a
      scaling principle different from the geometric similarity rule would be required
      in order for safety factors to remain similar among different-sized animals.
      Still, most comparable animals of 'similar kind' scale in accordance with the
      geometric similarity rule. Here, we instead argue that muscle forces cause much
      larger loads on structural support elements during maximum performance events
      (such as during prey capture or escape from predators) than do loads dictated by
      the body weight (such as during cruising locomotion), and that structural
      strength therefore might evolve with respect to maximal muscle forces rather than
      to the body weight. We explore how the transverse and longitudinal lengths of
      structural support elements must scale to one another, and to muscle transverse
      length, in order to satisfy each of the following, functionally based, similarity
      principles for support elements placed in bending, or in torsion, by maximal
      muscle forces during locomotion: (1) similarity in axial stress, or (2) in
      torsional shear stress, and (3) similarity in bent shape, or (4) in twisted
      shape. A dimensional relationship that satisfies all four conditions actually
      turns out to be the geometric similarity rule. These functional attributes may
      therefore help to explain the prevalence of geometric similarity among animals.
      Conformance of different-sized species with the geometric similarity principle
      has not been directly selected for as such, of course, but may have arisen as a
      by-product of adaptation in morphological proportions, following upon selection,
      in each separate species-lineage, for adequate and similar safety factors against
      breakage, and similar optimal distorted shapes, of structural support elements
      placed in bending, or in torsion, by maximal muscle forces.

PMID- 20675558
TI  - Tarsal taste neuron activity and proboscis extension reflex in response to sugars
      and amino acids in Helicoverpa armigera (Hubner).
AB  - In adult female Helicoverpa armigera (Hubner), the fifth tarsomere of the
      prothoracic legs bears 14 gustatory trichoid chemosensilla. These chemosensilla
      were characterized through electrophysiological experiments by stimulating with
      sucrose, glucose, fructose, maltose, myo-inositol and 20 common amino acids. In
      electrophysiological recordings from nine sensilla, responses were obtained to
      certain compounds tested at 100 mmol l(-1), and the response spectra differed
      from broad to narrow. The four sugars excited the same receptor neuron in
      sensillum a and sensillum b; sucrose and myo-inositol, sucrose and lysine, myo
      inositol and lysine excited two different receptor neurons respectively in
      sensillum a; fructose and lysine excited two different receptor neurons in
      sensillum n. Furthermore, the four sugars, myo-inositol and lysine all elicited
      concentration-dependent electrophysiological responses. These six compounds also
      induced the proboscis extension reflex (PER) followed by ingestion of the
      solution when they were applied on the tarsi. Lysine and sucrose caused the
      strongest electrophysiological responses. However, sucrose had the strongest
      stimulatory effect on the PER whereas lysine had the weakest. Mixtures of sucrose
      with the other sugars or with lysine had a similar stimulatory effect on the PER
      as sucrose alone. The electrophysiological and behavioural responses caused by a
      range of sucrose concentrations were positively correlated. We conclude that the
      tarsal gustatory sensilla play an essential role in perceiving sugars available
      in floral nectar and provide chemosensory information determining feeding
      behaviour. Tarsal taste-receptor-neuron responses to lysine are implicated in
      oviposition behaviour.

PMID- 20675560
TI  - The impact of radiation therapy in patients with diffuse large B-cell lymphoma
      with positive post-chemotherapy FDG-PET or gallium-67 scans.
AB  - BACKGROUND: 2-[fluorine-18]fluoro-2-deoxy-D-glucose-positron emission tomography
      (PET) and gallium-67 citrate (gallium) response after chemotherapy are powerful
      prognostic factors in diffuse large B-cell lymphoma (DLBCL). However, clinical
      outcomes when consolidation radiation therapy (RT) is administered are less
      defined. PATIENTS AND METHODS: We reviewed 99 patients diagnosed with DLBCL from
      1996 to 2007 at Duke University who had a post-chemotherapy response assessment
      with either PET or gallium and who subsequently received consolidation RT.
      Clinical outcomes were estimated using the Kaplan-Meier method and compared using
      the log-rank test. RESULTS: Median follow-up was 4.4 years. Stage distribution
      was I-II in 70% and III-IV in 30%. Chemotherapy was R-CHOP or CHOP in 88%. Median
      RT dose was 30 Gy. Post-chemotherapy PET (n = 79) or gallium (n = 20) was
      positive in 21 of 99 patients and negative in 78 of 99 patients. Five-year in
      field control was 95% with a negative PET/gallium scan versus 71% with a positive
      scan (P < 0.01). Five-year event-free survival (EFS; 83% versus 65%, P = 0.04)
      and overall survival (89% versus 73%, P = 0.04) were also significantly better
      when the post-chemotherapy PET/gallium was negative. CONCLUSIONS: A positive
      PET/gallium scan after chemotherapy is associated with an increased risk of local
      failure and death. Consolidation RT, however, still results in long-term EFS in
      65% of patients.

PMID- 20675559
TI  - Clinical validation of an autoantibody test for lung cancer.
AB  - BACKGROUND: Autoantibodies may be present in a variety of underlying cancers
      several years before tumours can be detected and testing for their presence may
      allow earlier diagnosis. We report the clinical validation of an autoantibody
      panel in newly diagnosed patients with lung cancer (LC). PATIENTS AND METHODS:
      Three cohorts of patients with newly diagnosed LC were identified: group 1 (n =
      145), group 2 (n = 241) and group 3 (n = 269). Patients were individually matched
      by gender, age and smoking history to a control individual with no history of
      malignant disease. Serum samples were obtained after diagnosis but before any
      anticancer treatment. Autoantibody levels were measured against a panel of six
      tumour-related antigens (p53, NY-ESO-1, CAGE, GBU4-5, Annexin 1 and SOX2). Assay
      sensitivity was tested in relation to demographic variables and cancer
      type/stage. RESULTS: The autoantibody panel demonstrated a
      sensitivity/specificity of 36%/91%, 39%/89% and 37%/90% in groups 1, 2 and 3,
      respectively, with good reproducibility. There was no significant difference
      between different LC stages, indicating that the antigens included covered the
      different types of LC well. CONCLUSION: This assay confirms the value of an
      autoantibody panel as a diagnostic tool and offers a potential system for
      monitoring patients at high risk of LC.

PMID- 20675561
TI  - Misrepresentation.

PMID- 20675562
TI  - Differential effects on nitric oxide-mediated vasodilation in mesenteric and
      uterine arteries from cytomegalovirus-infected mice.
AB  - Chronic cytomegalovirus (CMV) infections are implicated in vascular diseases.
      Recently, we showed that an active mouse CMV (mCMV) infection in nonpregnant mice
      increased endothelial-dependent vasodilation in isolated mesenteric and uterine
      arteries. In late pregnancy, while increased vasodilation was found in mesenteric
      arteries from infected mice, there was a dramatic decrease in uterine arteries.
      Understanding the mechanisms for these vascular changes during CMV infections is
      important for pregnancy outcomes and long-term consequences of this chronic
      infection. Increased nitric oxide (NO) is implicated in CMV-associated
      atherosclerosis, and CMV replication is dependent on prostaglandin H synthase
      (PGHS) activity. Alternatively, CMV infections decrease NO under inflammatory
      conditions. We therefore hypothesized that changes in the contribution by NO or
      PGHS-induced vasodilators would explain the increased or decreased endothelial
      dependent vasodilation in arteries from nonpregnant and late pregnant mice,
      respectively. We found that the contribution by NO to methacholine-induced
      vasodilation was significantly increased in mesenteric, but not uterine, arteries
      isolated from nonpregnant and pregnant mCMV-infected mice. Prostaglandin
      inhibition did not affect endothelial-dependent vasodilation in any group.
      Vasodilation responses to sodium nitroprusside, an NO donor, were increased in
      mesenteric and uterine arteries isolated only from mCMV-infected nonpregnant
      mice. These results explain the increased vasodilation responses observed in
      mesenteric arteries from mCMV-infected mice; however, the decreased vasodilation
      in uterine arteries from pregnant mice could not be explained by these
      mechanisms. Thus CMV infection affects the contribution of NO differently in
      endothelial-dependent vasodilation in pregnant compared with nonpregnant mice and
      also in the mesenteric compared with the uterine vascular bed.

PMID- 20675564
TI  - Left ventricular underfilling and not septal bulging dominates abnormal left
      ventricular filling hemodynamics in chronic thromboembolic pulmonary
      hypertension.
AB  - Chronic thromboembolic pulmonary hypertension (CTEPH) is associated with abnormal
      left ventricular (LV) filling hemodynamics [mitral early passive filling wave
      velocity/late active filling wave velocity (E/A) < 1]. Pulmonary endarterectomy
      (PEA) acutely reduces pulmonary vascular resistance, resulting in an increase of
      mitral E/A. The abolishment of leftward septal bulging and an increase in right
      ventricular (RV) output are thought to be responsible for the increase of mitral
      E/A. In this study, we quantified the separate effects of leftward septal bulging
      and RV output on LV hemodynamics. In 39 CTEPH patients who underwent PEA,
      transmitral flow velocities and RV hemodynamic data were obtained pre- and
      postoperatively. A mathematical model describing the mechanics of ventricular
      interaction was fitted to the preoperative average values of cardiac output (CO;
      4.4 l/min), mean pulmonary artery pressure (mPAP; 50 mmHg), mitral E/A (0.74),
      and mean left atrial pressure (mLAP; 9.8 mmHg). Starting from this preoperative
      reference state with leftward septal bulging, PEA was simulated by changing mPAP
      and CO to average postoperative values (28 mmHg and 5.7 l/min, respectively).
      Simulated and postoperatively measured data on E/A (1.27 vs. 1.48), mLAP (12.6
      vs. 11.5 mmHg), and septal curvature (both rightward) were consistent. When an
      exclusive decrease of mPAP was simulated, mitral E/A increased 26%, mLAP
      decreased 16%, and septal curvature became rightward. When an exclusive increase
      of CO was simulated, mitral E/A increased 53% and mLAP increased 62%, whereas
      leftward septal bulging persisted. Thus, our simulations suggest that the
      increase of mitral E/A with PEA is caused two-thirds by an increase of RV output
      and one-third by the abolishment of leftward septal bulging.

PMID- 20675563
TI  - Angiotensin-(1-7) upregulates cardiac nitric oxide synthase in spontaneously
      hypertensive rats.
AB  - It has been shown that angiotensin (ANG)-(1-7) activates nitric oxide synthase
      (NOS) in isolated ventricular myocytes from normotensive rats. Since many ANG-(1
      7) actions are enhanced in situations of increased ANG II activity, as in
      hypertension, in this study we investigated the in vivo effect of ANG-(1-7) on
      NOS activity and expression of endothelial (eNOS), neuronal (nNOS), and inducible
      NOS (iNOS) in ventricles from spontaneously hypertensive rats (SHR). Rats were
      subjected to a 60-min ANG-(1-7) infusion (0.35 nmol/min); controls received
      saline. NOS activity was measured using the NADPH diaphorase histochemical method
      and by the conversion of L-[(14)C]arginine to citrulline, and NOS phosphorylation
      and expression were determined using Western blotting. In SHR, ANG-(1-7) infusion
      diminished mean arterial pressure from 180 +/- 9 to 146 +/- 9 mmHg (P < 0.05),
      and this effect was prevented by nitro-l-arginine methyl ester (l-NAME), a NOS
      inhibitor. In addition, NOS activity and eNOS phosphorylation were increased by
      ANG-(1-7) infusion. Ventricular eNOS and nNOS expression were increased 67.4 +/-
      6.4 and 51 +/- 10%, respectively, by ANG-(1-7), whereas iNOS was not changed. In
      another set of experiments, we evaluated the mechanism by which ANG-(1-7)
      modifies NOS activity. Isolated ventricle slices preincubated with ANG-(1-7)
      showed an increase in NOS activity and eNOS phosphorylation, which was blocked by
      an AT(2) and a bradykinin B(2) receptor antagonist, but not by the Mas receptor
      antagonist. Our results show that in rats in a hypertensive state, ANG-(1-7)
      infusion upregulates cardiac NOS expression and activity through an AT(2)- and
      bradykinin-dependent mechanism. In this way ANG-(1-7) may elicit its
      cardioprotective action and contribute to some of the counterregulatory AT(2)
      receptor effects that oppose the AT(1) receptor-mediated effects.

PMID- 20675565
TI  - Early activation of matrix metalloproteinases underlies the exacerbated systolic
      and diastolic dysfunction in mice lacking TIMP3 following myocardial infarction.
AB  - Extracellular matrix (ECM) remodeling is a critical aspect of cardiac remodeling
      following myocardial infarction. Tissue inhibitors of metalloproteinases (TIMPs)
      are physiological inhibitors of matrix metalloproteinases (MMPs) that degrade the
      ECM proteins. TIMP3 is highly expressed in the heart, and is markedly
      downregulated in patients with ischemic cardiomyopathy. We therefore examined the
      time- and region-dependent role of TIMP3 in the cardiac response to myocardial
      infarction (MI). TIMP3(-/-) and wild-type (WT) mice were subjected to MI by
      ligation of the left anterior descending artery. TIMP3(-/-)-MI mice exhibited a
      significantly compromised rate of survival compared with WT-MI mice, primarily
      due to increased left ventricular (LV) rupture, greater infarct expansion,
      exacerbated LV dilation, and greater systolic and diastolic dysfunction. Second
      harmonic generation imaging of unfixed and unstained hearts revealed greater
      collagen disarray and reduced density in the TIMP3(-/-) infarct myocardium
      compared with the WT group. Gelatinolytic and collagenolytic activities increased
      in TIMP3(-/-) compared with WT hearts at 1 day post-MI but not at 3 days or 1 wk
      post-MI. Neutrophil infiltration and inflammatory MMPs were significantly
      increased in the infarct and peri-infarct regions of TIMP3(-/-)-MI hearts.
      Treatment of TIMP3(-/-) mice with a broad-spectrum MMP inhibitor (PD-166793) for
      2 days before and 2 days after MI markedly improved post-MI infarct expansion, LV
      rupture incident, LV dilation, and systolic dysfunction in these mice up to 1 wk
      post-MI. Our data demonstrate that the initial rise in proteolytic activities
      early post-MI is a triggering factor for subsequent LV adverse remodeling, LV
      rupture, and dilated cardiomyopathy. Hence, timing of treatments to improve
      cardiac response to MI may be critical in producing favorable outcome.

PMID- 20675566
TI  - Resveratrol improves left ventricular diastolic relaxation in type 2 diabetes by
      inhibiting oxidative/nitrative stress: in vivo demonstration with magnetic
      resonance imaging.
AB  - Resveratrol is a natural phytophenol that exhibits cardioprotective effects. This
      study was designed to elucidate the mechanisms by which resveratrol protects
      against diabetes-induced cardiac dysfunction. Normal control (m-Lepr(db)) mice
      and type 2 diabetic (Lepr(db)) mice were treated with resveratrol orally for 4
      wk. In vivo MRI showed that resveratrol improved cardiac function by increasing
      the left ventricular diastolic peak filling rate in Lepr(db) mice. This
      protective role is partially explained by resveratrol's effects in improving
      nitric oxide (NO) production and inhibiting oxidative/nitrative stress in cardiac
      tissue. Resveratrol increased NO production by enhancing endothelial NO synthase
      (eNOS) expression and reduced O(2)(.-) production by inhibiting NAD(P)H oxidase
      activity and gp91(phox) mRNA and protein expression. The increased nitrotyrosine
      (N-Tyr) protein expression in Lepr(db) mice was prevented by the inducible NO
      synthase (iNOS) inhibitor 1400W. Resveratrol reduced both N-Tyr and iNOS
      expression in Lepr(db) mice. Furthermore, TNF-alpha mRNA and protein expression,
      as well as NF-kappaB activation, were reduced in resveratrol-treated Lepr(db)
      mice. Both Lepr(db) mice null for TNF-alpha (db(TNF-)/db(TNF-) mice) and Lepr(db)
      mice treated with the NF-kappaB inhibitor MG-132 showed decreased NAD(P)H oxidase
      activity and iNOS expression as well as elevated eNOS expression, whereas m
      Lepr(db) mice treated with TNF-alpha showed the opposite effects. Thus,
      resveratrol protects against cardiac dysfunction by inhibiting
      oxidative/nitrative stress and improving NO availability. This improvement is due
      to the role of resveratrol in inhibiting TNF-alpha-induced NF-kappaB activation,
      therefore subsequently inhibiting the expression and activation of NAD(P)H
      oxidase and iNOS as well as increasing eNOS expression in type 2 diabetes.

PMID- 20675567
TI  - Differential mechanisms of inhibition of glyceraldehyde-3-phosphate dehydrogenase
      by S-nitrosothiols and NO in cellular and cell-free conditions.
AB  - S-nitrosothiols are nitric oxide (NO)-derived molecules found in biological
      systems. They have been variously discussed as both NO reservoirs and as major
      actors in NO-dependent, but cGMP-independent, signal transduction. Although S
      nitrosation of specific cysteine residues has been suggested to represent a novel
      redox-based signaling mechanism, the exact mechanisms of S-nitrosothiol formation
      under (patho)physiological conditions and the determinants of signaling
      specificity have not yet been established. Here we examined the sensitivity of
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH) to inhibition by S
      nitrosocysteine (CysNO) and NO both intracellularly and in isolation. Bovine
      aortic endothelial cells (BAECs) and purified GAPDH preparations were treated
      with CysNO or NO, and enzymatic activity was monitored. Intracellular GAPDH was
      irreversibly inhibited upon CysNO administration, whereas treatment with NO
      resulted in a DTT-reversible inhibition of the enzyme. Purified GAPDH was
      inhibited by both CysNO and NO, but the inhibition pattern was diametrically
      opposite to that observed in the cells; CysNO-dependent inhibition was reversed
      with DTT, whereas NO-dependent inhibition was not. In the presence of GSH, NO
      inhibited purified GAPDH in a DTT-reversible way. Our data suggest that in
      response to CysNO treatment, cellular GAPDH undergoes S-nitrosation, which
      results in an irreversible inhibition of the enzyme under turnover conditions. In
      contrast, NO inhibits the enzyme via oxidative mechanisms that do not involve S
      nitrosation and are reversible. In summary, our data show that GAPDH is a target
      for CysNO- and NO-dependent inhibition; however, these two agents inhibit the
      enzyme via different mechanisms both inside the cell and in isolation.
      Additionally, the differences observed between the cellular system and purified
      protein strongly imply that the intracellular environment dictates the mechanism
      of inhibition.

PMID- 20675568
TI  - 20-HETE increases NADPH oxidase-derived ROS production and stimulates the L-type
      Ca2+ channel via a PKC-dependent mechanism in cardiomyocytes.
AB  - The production of 20-hydroxyeicosatetraenoic acid (20-HETE) is increased during
      ischemia-reperfusion, and inhibition of 20-HETE production has been shown to
      reduce infarct size caused by ischemia. This study was aimed to discover the
      molecular mechanism underlying the action of 20-HETE in cardiac myocytes. The
      effect of 20-HETE on L-type Ca(2+) currents (I(Ca,L)) was examined in rat
      isolated cardiomyocytes by patch-clamp recording in the whole cell mode.
      Superfusion of cardiomyocytes with 20-HETE (10-100 nM) resulted in a
      concentration-dependent increase in I(Ca,L), and this action of 20-HETE was
      attenuated by a specific NADPH oxidase inhibitor, gp91ds-tat (5 MUM), or a
      superoxide scavenger, polyethylene glycol-superoxide dismutase (25 U/ml),
      suggesting that NADPH-oxidase-derived superoxide is involved in the stimulatory
      action of 20-HETE on I(Ca,L). Treatment of cardiomyocytes with 20-HETE (100 nM)
      increased both NADPH oxidase activity and superoxide production by approximately
      twofold. To study the molecular mechanism mediating the 20-HETE-induced increase
      in NADPH oxidase activity, PKC activity was measured in cardiomyocytes.
      Incubation of the cells with 20-HETE (100 nM) significantly increased PKC
      activity, and pretreatment of cardiomyocytes with a selective PKC inhibitor, GF
      109203 (1 MUM), attenuated the 20-HETE-induced increases in I(Ca,L) and in NADPH
      oxidase activity. In summary, 20-HETE stimulates NADPH oxidase-derived superoxide
      production, which activates L-type Ca(2+) channels via a PKC-dependent mechanism
      in cardiomyocytes. 20-HETE and 20-HETE-producing enzymes could be novel targets
      for the treatment of cardiac ischemic diseases.

PMID- 20675569
TI  - Regulation of CYP2C19 expression by estrogen receptor alpha: implications for
      estrogen-dependent inhibition of drug metabolism.
AB  - Cytochrome P4502C19 (CYP2C19) is an important drug-metabolizing enzyme involved
      in the biotransformation of, for example, proton pump inhibitors and
      antidepressants. Several in vivo studies have shown that the CYP2C19 activity is
      inhibited by oral contraceptives, which can cause important drug interactions.
      The underlying molecular mechanism has been suggested to be competitive
      inhibition. However, the results presented here indicate that estradiol
      derivatives down-regulate CYP2C19 expression via estrogen receptor (ER) alpha,
      which interacts with the newly identified ER-binding half site [estrogen response
      element (ERE)] at the position -151/-147 in the CYP2C19 promoter. In gene
      reporter experiments in Huh-7 hepatoma cells, the activity of the luciferase
      construct carrying a 1.6-kb long CYP2C19 promoter fragment cotransfected with
      ERalpha was down-regulated upon treatment with 17beta-estradiol (EE) or 17alpha
      ethinylestradiol (ETE) at half-maximum concentrations of 10(-7) and 10(-8) M,
      respectively. Mutations introduced into the ERE half site -151/-147 significantly
      inhibited these ligand-dependent effects. Electrophoretic mobility shift assays
      and quantitative chromatin immunoprecipitation experiments revealed that estrogen
      receptor alpha binds to this element. A significant suppression of CYP2C19
      transcription by female sex steroids was confirmed by reverse transcription
      polymerase chain reaction after hormonal treatment of human hepatocytes.
      Inhibition experiments using a stable human embryonic kidney 293 CYP2C19 cell
      line revealed competitive inhibition at much higher concentrations of EE and ETE
      compared with those required for transcriptional inhibition. These results
      indicate that both EE and ETE inhibit CYP2C19 expression via an ERalpha-dependent
      regulatory pathway, thus providing a new insight into the molecular mechanism
      behind the inhibitory effect of oral contraceptives on CYP2C19 activity.

PMID- 20675570
TI  - Regulation of cell proliferation in the stomatal lineage by the Arabidopsis MYB
      FOUR LIPS via direct targeting of core cell cycle genes.
AB  - Stomata, which are epidermal pores surrounded by two guard cells, develop from a
      specialized stem cell lineage and function in shoot gas exchange. The Arabidopsis
      thaliana FOUR LIPS (FLP) and MYB88 genes encode closely related and atypical two
      MYB-repeat proteins, which when mutated result in excess divisions and abnormal
      groups of stomata in contact. Consistent with a role in transcription, we show
      here that FLP and MYB88 are nuclear proteins with DNA binding preferences
      distinct from other known MYBs. To identify possible FLP/MYB88 transcriptional
      targets, we used chromatin immunoprecitation (ChIP) followed by hybridization to
      Arabidopsis whole genome tiling arrays. These ChIP-chip data indicate that
      FLP/MYB88 target the upstream regions especially of cell cycle genes, including
      cyclins, cyclin-dependent kinases (CDKs), and components of the prereplication
      complex. In particular, we show that FLP represses the expression of the mitosis
      inducing factor CDKB1;1, which, along with CDKB1;2, is specifically required both
      for the last division in the stomatal pathway and for cell overproliferation in
      flp mutants. We propose that FLP and MYB88 together integrate patterning with the
      control of cell cycle progression and terminal differentiation through multiple
      and direct cell cycle targets. FLP recognizes a distinct cis-regulatory element
      that overlaps with that of the cell cycle activator E2F-DP in the CDKB1;1
      promoter, suggesting that these MYBs may also modulate E2F-DP pathways.

PMID- 20675571
TI  - The bHLH transcription factor POPEYE regulates response to iron deficiency in
      Arabidopsis roots.
AB  - Global population increases and climate change underscore the need for better
      comprehension of how plants acquire and process nutrients such as iron. Using
      cell type-specific transcriptional profiling, we identified a pericycle-specific
      iron deficiency response and a bHLH transcription factor, POPEYE (PYE), that may
      play an important role in this response. Functional analysis of PYE suggests that
      it positively regulates growth and development under iron-deficient conditions.
      Chromatin immunoprecipitation-on-chip analysis and transcriptional profiling
      reveal that PYE helps maintain iron homeostasis by regulating the expression of
      known iron homeostasis genes and other genes involved in transcription,
      development, and stress response. PYE interacts with PYE homologs, including IAA
      Leu Resistant3 (ILR3), another bHLH transcription factor that is involved in
      metal ion homeostasis. Moreover, ILR3 interacts with a third protein, BRUTUS
      (BTS), a putative E3 ligase protein, with metal ion binding and DNA binding
      domains, which negatively regulates the response to iron deficiency. PYE and BTS
      expression is also tightly coregulated. We propose that interactions among PYE,
      PYE homologs, and BTS are important for maintaining iron homeostasis under low
      iron conditions.

PMID- 20675572
TI  - NENA, a Lotus japonicus homolog of Sec13, is required for rhizodermal infection
      by arbuscular mycorrhiza fungi and rhizobia but dispensable for cortical
      endosymbiotic development.
AB  - Legumes form symbioses with arbuscular mycorrhiza (AM) fungi and nitrogen fixing
      root nodule bacteria. Intracellular root infection by either endosymbiont is
      controlled by the activation of the calcium and calmodulin-dependent kinase
      (CCaMK), a central regulatory component of the plant's common symbiosis signaling
      network. We performed a microscopy screen for Lotus japonicus mutants defective
      in AM development and isolated a mutant, nena, that aborted fungal infection in
      the rhizodermis. NENA encodes a WD40 repeat protein related to the nucleoporins
      Sec13 and Seh1. Localization of NENA to the nuclear rim and yeast two-hybrid
      experiments indicated a role for NENA in a conserved subcomplex of the nuclear
      pore scaffold. Although nena mutants were able to form pink nodules in symbiosis
      with Mesorhizobium loti, root hair infection was not observed. Moreover, Nod
      factor induction of the symbiotic genes NIN, SbtM4, and SbtS, as well as
      perinuclear calcium spiking, were impaired. Detailed phenotypic analyses of nena
      mutants revealed a rhizobial infection mode that overcame the lack of rhizodermal
      responsiveness and carried the hallmarks of crack entry, including a requirement
      for ethylene. CCaMK-dependent processes were only abolished in the rhizodermis
      but not in the cortex of nena mutants. These data support the concept of tissue
      specific components for the activation of CCaMK.

PMID- 20675573
TI  - Orchestration of the floral transition and floral development in Arabidopsis by
      the bifunctional transcription factor APETALA2.
AB  - The Arabidopsis thaliana transcription factor APETALA2 (AP2) has numerous
      functions, including roles in seed development, stem cell maintenance, and
      specification of floral organ identity. To understand the relationship between
      these different roles, we mapped direct targets of AP2 on a genome-wide scale in
      two tissue types. We find that AP2 binds to thousands of loci in the developing
      flower, many of which exhibit AP2-dependent transcription. Opposing, logical
      effects are evident in AP2 binding to two microRNA genes that influence AP2
      expression, with AP2 positively regulating miR156 and negatively regulating
      miR172, forming a complex direct feedback loop, which also included all but one
      of the AP2-like miR172 target clade members. We compare the genome-wide direct
      target repertoire of AP2 with that of SCHLAFMUTZE, a closely related
      transcription factor that also represses the transition to flowering. We detect
      clear similarities and important differences in the direct target repertoires
      that are also tissue specific. Finally, using an inducible expression system, we
      demonstrate that AP2 has dual molecular roles. It functions as both a
      transcriptional activator and repressor, directly inducing the expression of the
      floral repressor AGAMOUS-LIKE15 and directly repressing the transcription of
      floral activators like SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1.

PMID- 20675574
TI  - The tig1 histone deacetylase complex regulates infectious growth in the rice
      blast fungus Magnaporthe oryzae.
AB  - Magnaporthe oryzae is the most damaging fungal pathogen of rice (Oryza sativa).
      In this study, we characterized the TIG1 transducin beta-like gene required for
      infectious growth and its interacting genes that are required for plant infection
      in this model phytopathogenic fungus. Tig1 homologs in yeast and mammalian cells
      are part of a conserved histone deacetylase (HDAC) transcriptional corepressor
      complex. The tig1 deletion mutant was nonpathogenic and defective in
      conidiogenesis. It had an increased sensitivity to oxidative stress and failed to
      develop invasive hyphae in plant cells. Using affinity purification and
      coimmunoprecipitation assays, we identified several Tig1-associated proteins,
      including two HDACs that are homologous to components of the yeast Set3 complex.
      Functional analyses revealed that TIG1, SET3, SNT1, and HOS2 were core components
      of the Tig1 complex in M. oryzae. The set3, snt1, and hos2 deletion mutants
      displayed similar defects as those observed in the tig1 mutant, but deletion of
      HST1 or HOS4 had no detectable phenotypes. Deletion of any of these core
      components of the Tig1 complex resulted in a significant reduction in HDAC
      activities. Our results showed that TIG1, like its putative yeast and mammalian
      orthologs, is one component of a conserved HDAC complex that is required for
      infectious growth and conidiogenesis in M. oryzae and highlighted that chromatin
      modification is an essential regulatory mechanism during plant infection.

PMID- 20675575
TI  - Environmental regulation of lateral root emergence in Medicago truncatula
      requires the HD-Zip I transcription factor HB1.
AB  - The adaptation of root architecture to environmental constraints is a major
      agricultural trait, notably in legumes, the third main crop worldwide. This root
      developmental plasticity depends on the formation of lateral roots (LRs) emerging
      from primary roots. In the model legume Medicago truncatula, the HD-Zip I
      transcription factor HB1 is expressed in primary and lateral root meristems and
      induced by salt stress. Constitutive expression of HB1 in M. truncatula roots
      alters their architecture, whereas hb1 TILLING mutants showed increased lateral
      root emergence. Electrophoretic mobility shift assay, promoter mutagenesis, and
      chromatin immunoprecipitation-PCR assays revealed that HB1 directly recognizes a
      CAATAATTG cis-element present in the promoter of a LOB-like (for Lateral Organ
      Boundaries) gene, LBD1, transcriptionally regulated by auxin. Expression of these
      genes in response to abscisic acid and auxin and their behavior in hb1 mutants
      revealed an HB1-mediated repression of LBD1 acting during LR emergence. M.
      truncatula HB1 regulates an adaptive developmental response to minimize the root
      surface exposed to adverse environmental stresses.

PMID- 20675576
TI  - Role of Aspergillus fumigatus DvrA in host cell interactions and virulence.
AB  - The transcription factors that regulate Aspergillus fumigatus interactions with
      host cells and virulence are incompletely defined. We investigated the role of
      the putative C2H2 transcription factor DvrA in governing these processes.
      Although DvrA was identified by its limited homology to Candida albicans Bcr1, a
      DeltadvrA mutant strain of A. fumigatus had wild-type adherence to host
      constituents in vitro. However, it had increased capacity to damage both
      endothelial cells and a pulmonary epithelial cell line compared to the ability of
      the wild-type strain and a DeltadvrA::dvrA-complemented strain. This increase in
      damage required direct contact between the mutant and host cells. The DeltadvrA
      mutant also stimulated greater CCL20, interleukin-8, and tumor necrosis factor
      mRNA expression in a pulmonary epithelial cell line compared to levels induced by
      the control strains. Also, it was resistant to nikkomycin Z, suggesting an
      altered cell wall composition. As predicted by these in vitro results, the
      DeltadvrA mutant had increased virulence and stimulated a greater pulmonary
      inflammatory response than the wild-type strain and DeltadvrA::dvrA-complemented
      strains in the nonneutropenic mouse model of invasive pulmonary aspergillosis.
      These results indicate that DvrA influences A. fumigatus virulence as well as its
      capacity to damage host cells and stimulate a proinflammatory response.

PMID- 20675577
TI  - Identification of GIG1, a GlcNAc-induced gene in Candida albicans needed for
      normal sensitivity to the chitin synthase inhibitor nikkomycin Z.
AB  - The amino sugar N-acetylglucosamine (GlcNAc) is known to be an important
      structural component of cells from bacteria to humans, but its roles in cell
      signaling are less well understood. GlcNAc induces two pathways in the human
      fungal pathogen Candida albicans. One activates cyclic AMP (cAMP) signaling,
      which stimulates the formation of hyphal cells and the expression of virulence
      genes, and the other pathway induces genes needed to catabolize GlcNAc.
      Microarray analysis of gene expression was carried out under four different
      conditions in order to characterize the transcriptional changes induced by
      GlcNAc. The most highly induced genes include those that encode a GlcNAc
      transporter (NGT1) and the GlcNAc catabolic enzymes (HXK1, DAC1, and NAG1).
      GlcNAc also activated most of the genes whose expression is increased when cells
      are triggered with other stimuli to form hyphae. Surprisingly, GlcNAc also
      induced a subset of genes that are regulated by galactose (GAL1, GAL7, and
      GAL10), which may be due to cross talk between signaling pathways. A novel GlcNAc
      induced gene, GIG1, which is not essential for GlcNAc catabolism or the induction
      of hyphae, was identified. However, a Gig1-green fluorescent protein (GFP) fusion
      protein was specifically induced by GlcNAc, and not by other sugars. Gig1-GFP
      localized to the cytoplasm, where GlcNAc metabolism occurs. Significantly, a
      gig1Delta mutant displayed increased resistance to nikkomycin Z, which inhibits
      chitin synthase from converting UDP-GlcNAc into cell wall chitin. Gig1 is highly
      conserved in fungi, especially those that contain GlcNAc catabolic genes. These
      results implicate Gig1 in GlcNAc metabolism.

PMID- 20675578
TI  - Sulfate assimilation mediates tellurite reduction and toxicity in Saccharomyces
      cerevisiae.
AB  - Despite a century of research and increasing environmental and human health
      concerns, the mechanistic basis of the toxicity of derivatives of the metalloid
      tellurium, Te, in particular the oxyanion tellurite, Te(IV), remains unsolved.
      Here, we provide an unbiased view of the mechanisms of tellurium metabolism in
      the yeast Saccharomyces cerevisiae by measuring deviations in Te-related traits
      of a complete collection of gene knockout mutants. Reduction of Te(IV) and
      intracellular accumulation as metallic tellurium strongly correlated with loss of
      cellular fitness, suggesting that Te(IV) reduction and toxicity are causally
      linked. The sulfate assimilation pathway upstream of Met17, in particular, the
      sulfite reductase and its cofactor siroheme, was shown to be central to tellurite
      toxicity and its reduction to elemental tellurium. Gene knockout mutants with
      altered Te(IV) tolerance also showed a similar deviation in tolerance to both
      selenite and, interestingly, selenomethionine, suggesting that the toxicity of
      these agents stems from a common mechanism. We also show that Te(IV) reduction
      and toxicity in yeast is partially mediated via a mitochondrial respiratory
      mechanism that does not encompass the generation of substantial oxidative stress.
      The results reported here represent a robust base from which to attack the
      mechanistic details of Te(IV) toxicity and reduction in a eukaryotic organism.

PMID- 20675579
TI  - Transcription factors in light and circadian clock signaling networks revealed by
      genomewide mapping of direct targets for neurospora white collar complex.
AB  - Light signaling pathways and circadian clocks are inextricably linked and have
      profound effects on behavior in most organisms. Here, we used chromatin
      immunoprecipitation (ChIP) sequencing to uncover direct targets of the Neurospora
      crassa circadian regulator White Collar Complex (WCC). The WCC is a blue-light
      receptor and the key transcription factor of the circadian oscillator. It
      controls a transcriptional network that regulates ~20% of all genes, generating
      daily rhythms and responses to light. We found that in response to light, WCC
      binds to hundreds of genomic regions, including the promoters of previously
      identified clock- and light-regulated genes. We show that WCC directly controls
      the expression of 24 transcription factor genes, including the clock-controlled
      adv-1 gene, which controls a circadian output pathway required for daily rhythms
      in development. Our findings provide links between the key circadian activator
      and effectors in downstream regulatory pathways.

PMID- 20675580
TI  - Functional characterization of three leishmania poly(a) binding protein
      homologues with distinct binding properties to RNA and protein partners.
AB  - Trypanosomatid protozoans are reliant on posttranscriptional processes to control
      gene expression. Regulation occurs at the levels of mRNA processing, stability,
      and translation, events that may require the participation of the poly(A) binding
      protein (PABP). Here, we have undertaken a functional study of the three distinct
      Leishmania major PABP (LmPABP) homologues: the previously described LmPABP1;
      LmPABP2, orthologous to the PABP described from Trypanosoma species; and LmPABP3,
      unique to Leishmania. Sequence identity between the three PABPs is no greater
      than 40%. In assays measuring binding to A-rich sequences, LmPABP1 binding was
      poly(A) sensitive but heparin insensitive; LmPABP2 binding was heparin sensitive
      and less sensitive to poly(A), compatible with unique substitutions observed in
      residues implicated in poly(A) binding; and LmPABP3 displayed intermediate
      properties. All three homologues are simultaneously expressed as abundant
      cytoplasmic proteins in L. major promastigotes, but only LmPABP1 is present as
      multiple isoforms. Upon transcription inhibition, LmPABP2 and -3 migrated to the
      nucleus, while LmPABP1 remained predominantly cytoplasmic. Immunoprecipitation
      assays showed an association between LmPABP2 and -3. Although the three proteins
      bound to a Leishmania homologue of the translation initiation factor eukaryotic
      initiation factor 4G (eIF4G) (LmEIF4G3) in vitro, LmPABP1 was the only one to
      copurify with native LmEIF4G3 from cytoplasmic extracts. Functionality was tested
      using RNA interference (RNAi) in Trypanosoma brucei, where both orthologues to
      LmPABP1 and -2 are required for cellular viability. Our results indicate that
      these homologues have evolved divergent functions, some of which may be unique to
      the trypanosomatids, and reinforces a role for LmPABP1 in translation through its
      interaction with the eIF4G homologue.

PMID- 20675581
TI  - Subtelomeric silencing of the MTL3 locus of Candida glabrata requires yKu70,
      yKu80, and Rif1 proteins.
AB  - Candida glabrata is a haploid opportunistic fungal pathogen that is
      phylogenetically related to Saccharomyces cerevisiae. Even though C. glabrata has
      no known sexual cycle, it contains, like S. cerevisiae, three mating type-like
      loci (MTL) called MTL1, MTL2, and MTL3, as well as most of the genes required for
      mating, meiosis, and sporulation. MTL1 is localized at an internal position on
      chromosome B and is thought to be the locus corresponding to the MAT locus in S.
      cerevisiae. MTL2 and MTL3 are localized close to two telomeres on different
      chromosomes (29.4 kb from Chr E-L and 10.5 kb from Chr B-L, respectively). By
      using URA3 reporter gene insertions at the three MTL loci, we found that in
      contrast to the case for S. cerevisiae, only MTL3 is subject to transcriptional
      silencing while MTL2 is transcriptionally active, and this is in agreement with
      previously reported data. We found that the silencing of MTL3 is nucleated
      primarily at the left telomere of chromosome B and spreads over 12 kb to MTL3,
      rather than nucleating at flanking, closely positioned cis-acting silencers, like
      those flanking HMR and HML of S. cerevisiae. Interestingly, the silencing of MTL3
      absolutely requires the yKu70, yKu80, and Rif1 proteins, in sharp contrast to the
      silencing of the HM loci of S. cerevisiae. In addition, we found that several
      cell type-specific genes are expressed in C. glabrata regardless of the presence,
      or even absence, of mating type information at any of the MTL loci.

PMID- 20675582
TI  - Arc expression and neuroplasticity in primary auditory cortex during initial
      learning are inversely related to neural activity.
AB  - Models of learning-dependent sensory cortex plasticity require local activity and
      reinforcement. An alternative proposes that neural activity involved in
      anticipation of a sensory stimulus, or the preparatory set, can direct plasticity
      so that changes could occur in regions of sensory cortex lacking activity. To
      test the necessity of target-induced activity for initial sensory learning, we
      trained rats to detect a low-frequency sound. After learning, Arc expression and
      physiologically measured neuroplasticity were strong in a high-frequency auditory
      cortex region with very weak target-induced activity in control animals. After 14
      sessions, Arc and neuroplasticity were aligned with target-induced activity. The
      temporal and topographic correspondence between Arc and neuroplasticity suggests
      Arc may be intrinsic to the neuroplasticity underlying perceptual learning.
      Furthermore, not all neuroplasticity could be explained by activity-dependent
      models but can be explained if the neural activity involved in the preparatory
      set directs plasticity.

PMID- 20675583
TI  - Cardiac conduction is required to preserve cardiac chamber morphology.
AB  - Electrical cardiac forces have been previously hypothesized to play a significant
      role in cardiac morphogenesis and remodeling. In response to electrical forces,
      cultured cardiomyocytes rearrange their cytoskeletal structure and modify their
      gene expression profile. To translate such in vitro data to the intact heart, we
      used a collection of zebrafish cardiac mutants and transgenics to investigate
      whether cardiac conduction could influence in vivo cardiac morphogenesis
      independent of contractile forces. We show that the cardiac mutant dco(s226)
      develops heart failure and interrupted cardiac morphogenesis following
      uncoordinated ventricular contraction. Using in vivo optical mapping/calcium
      imaging, we determined that the dco cardiac phenotype was primarily due to
      aberrant ventricular conduction. Because cardiac contraction and intracardiac
      hemodynamic forces can also influence cardiac development, we further analyzed
      the dco phenotype in noncontractile hearts and observed that disorganized
      ventricular conduction could affect cardiomyocyte morphology and subsequent heart
      morphogenesis in the absence of contraction or flow. By positional cloning, we
      found that dco encodes Gja3/Cx46, a gap junction protein not previously
      implicated in heart formation or function. Detailed analysis of the mouse Cx46
      mutant revealed the presence of cardiac conduction defects frequently associated
      with human heart failure. Overall, these in vivo studies indicate that cardiac
      electrical forces are required to preserve cardiac chamber morphology and may act
      as a key epigenetic factor in cardiac remodeling.

PMID- 20675584
TI  - Stress coping stimulates hippocampal neurogenesis in adult monkeys.
AB  - Coping with intermittent social stress is an essential aspect of living in
      complex social environments. Coping tends to counteract the deleterious effects
      of stress and is thought to induce neuroadaptations in corticolimbic brain
      systems. Here we test this hypothesis in adult squirrel monkey males exposed to
      intermittent social separations and new pair formations. These manipulations
      simulate conditions that typically occur in male social associations because of
      competition for limited access to residency in mixed-sex groups. As evidence of
      coping, we previously confirmed that cortisol levels initially increase and then
      are restored to prestress levels within several days of each separation and new
      pair formation. Follow-up studies with exogenous cortisol further established
      that feedback regulation of the hypothalamic-pituitary-adrenal axis is not
      impaired. Now we report that exposure to intermittent social separations and new
      pair formations increased hippocampal neurogenesis in squirrel monkey males.
      Hippocampal neurogenesis in rodents contributes to spatial learning performance,
      and in monkeys we found that spatial learning was enhanced in conditions that
      increased hippocampal neurogenesis. Corresponding changes were discerned in the
      expression of genes involved in survival and integration of adult-born granule
      cells into hippocampal neural circuits. These findings support recent indications
      that stress coping stimulates hippocampal neurogenesis in adult rodents.
      Psychotherapies designed to promote stress coping potentially have similar
      effects in humans with major depression.

PMID- 20675585
TI  - Efficient reprogramming of adult neural stem cells to monocytes by ectopic
      expression of a single gene.
AB  - Neural stem cells have a broad differentiation repertoire during embryonic
      development and can be reprogrammed to pluripotency comparatively easily. We
      report that adult neural stem cells can be reprogrammed at very high efficiency
      to monocytes, a differentiated fate of an unrelated somatic lineage, by ectopic
      expression of the Ets transcription factor PU.1. The reprogrammed cells display a
      marker profile and functional characteristics of monocytes and integrate into
      tissues after transplantation. The failure to reprogram lineage-committed neural
      cells to monocytes with PU.1 suggests that neural stem cells are uniquely
      amenable to reprogramming.

PMID- 20675586
TI  - Ribosomal protein L7Ae is a subunit of archaeal RNase P.
AB  - To the mounting evidence of nonribosomal functions for ribosomal proteins, we now
      add L7Ae as a subunit of archaeal RNase P, a ribonucleoprotein (RNP) that
      catalyzes 5'-maturation of precursor tRNAs (pre-tRNAs). We first demonstrate that
      L7Ae coelutes with partially purified Methanococcus maripaludis (Mma) RNase P
      activity. After establishing in vitro reconstitution of the single RNA with four
      previously known protein subunits (POP5, RPP21, RPP29, and RPP30), we show that
      addition of L7Ae to this RNase P complex increases the optimal reaction
      temperature and k(cat)/K(m) (by approximately 360-fold) for pre-tRNA cleavage to
      those observed with partially purified native Mma RNase P. We identify in the Mma
      RNase P RNA a putative kink-turn (K-turn), the structural motif recognized by
      L7Ae. The large stimulatory effect of Mma L7Ae on RNase P activity decreases to
      <or= 4% of wild type upon mutating either the conserved nucleotides in this K
      turn or amino acids in L7Ae shown to be essential for K-turn binding. The
      critical, multifunctional role of archaeal L7Ae in RNPs acting in tRNA processing
      (RNase P), RNA modification (H/ACA, C/D snoRNPs), and translation (ribosomes),
      especially by employing the same RNA-recognition surface, suggests coevolution of
      various translation-related functions, presumably to facilitate their coordinate
      regulation.

PMID- 20675587
TI  - B1 cells promote pancreas infiltration by autoreactive T cells.
AB  - The entry of autoreactive T cells into the pancreas is a critical checkpoint in
      the development of autoimmune diabetes. In this study, we identify a role for B1
      cells in this process using the DO11 x RIP-mOVA mouse model. In transgenic mice
      with islet-specific T cells, but no B cells, T cells are primed in the pancreatic
      lymph node but fail to enter the pancreas. Reconstitution of the B1 cell
      population by adoptive transfer permits extensive T cell pancreas infiltration.
      Reconstituted B1 cells traffic to the pancreas and modify expression of adhesion
      molecules on pancreatic vasculature, notably VCAM-1. Despite substantial pancreas
      infiltration, islet destruction is minimal unless regulatory T cells are
      depleted. These data identify a role for B1 cells in permitting circulating islet
      specific T cells to access their Ag-bearing tissue and emphasize the existence of
      multiple checkpoints to regulate autoimmune disease.

PMID- 20675588
TI  - Neutrophil functions and autoimmune arthritis in the absence of p190RhoGAP:
      generation and analysis of a novel null mutation in mice.
AB  - Beta(2) integrins of neutrophils play a critical role in innate immune defense,
      but they also participate in tissue destruction during autoimmune inflammation.
      p190RhoGAP (ArhGAP35), a regulator of Rho family small GTPases, is required for
      integrin signal transduction in fibroblasts. Prior studies have also suggested a
      role for p190RhoGAP in beta(2) integrin signaling in neutrophils. To directly
      test that possibility, we have generated a novel targeted mutation completely
      disrupting the p190RhoGAP-encoding gene in mice. p190RhoGAP deficiency led to
      perinatal lethality and defective neural development, precluding the analysis of
      neutrophil functions in adult p190RhoGAP(-/-) animals. This was overcome by
      transplantation of fetal liver cells from p190RhoGAP(-/-) fetuses into lethally
      irradiated wild-type recipients. Neutrophils from such p190RhoGAP(-/-) bone
      marrow chimeras developed normally and expressed normal levels of various cell
      surface receptors. Although p190RhoGAP(-/-) neutrophils showed moderate reduction
      of beta(2) integrin-mediated adherent activation, they showed mostly normal
      migration in beta(2) integrin-dependent in vitro and in vivo assays and normal
      beta(2) integrin-mediated killing of serum-opsonized Staphylococcus aureus and
      Escherichia coli. A neutrophil- and beta(2) integrin-dependent transgenic model
      of the effector phase of autoimmune arthritis also proceeded normally in
      p190RhoGAP(-/-) bone marrow chimeras. In contrast, all the above responses were
      completely blocked in CD18(-/-) neutrophils or CD18(-/-) bone marrow chimeras.
      These results suggest that p190RhoGAP likely does not play a major indispensable
      role in beta(2) integrin-mediated in vitro and in vivo neutrophil functions or
      the effector phase of experimental autoimmune arthritis.

PMID- 20675589
TI  - Tethering of intercellular adhesion molecule on target cells is required for LFA
      1-dependent NK cell adhesion and granule polarization.
AB  - Alpha(L)beta(2) integrin (LFA-1) has an important role in the formation of T cell
      and NK cell cytotoxic immunological synapses and in target cell killing. Binding
      of LFA-1 to ICAM on target cells promotes not only adhesion but also polarization
      of cytolytic granules in NK cells. In this study, we tested whether LFA-1
      dependent NK cell responses are regulated by the distribution and mobility of
      ICAM at the surface of target cells. We show that depolymerization of F-actin in
      NK-sensitive target cells abrogated LFA-1-dependent conjugate formation and
      granule polarization in primary NK cells. Degranulation, which is not controlled
      by LFA-1, was not impaired. Fluorescence recovery after photobleaching
      experiments and particle tracking by total internal reflection fluorescence
      microscopy revealed that ICAM-1 and ICAM-2 were distributed in largely immobile
      clusters. ICAM clusters were maintained and became highly mobile after actin
      depolymerization. Moreover, reducing ICAM-2 mobility on an NK-resistant target
      cell through expression of ezrin, an adaptor molecule that tethers proteins to
      the actin cytoskeleton, enhanced LFA-1-dependent adhesion and granule
      polarization. Finally, although NK cells kept moving over freely diffusible ICAM
      1 on a lipid bilayer, they bound and spread over solid-phase ICAM-1. We conclude
      that tethering, rather than clustering of ICAM, promotes proper signaling by LFA
      1 in NK cells. Our findings suggest that the lateral diffusion of integrin
      ligands on cells may be an important determinant of susceptibility to lysis by
      cytotoxic lymphocytes.

PMID- 20675590
TI  - Roles for TGF-beta and programmed cell death 1 ligand 1 in regulatory T cell
      expansion and diabetes suppression by zymosan in nonobese diabetic mice.
AB  - Zymosan is a complex fungal component shown to be capable of both promoting and
      suppressing the development of autoimmune disorders in mice. In this study, we
      show that a single injection of zymosan just prior to diabetes onset can
      significantly delay the progression of disease in NOD mice. Zymosan treatment of
      NOD mice induced the production of biologically active TGF-beta from cells
      infiltrating the pancreas and was associated with expansion of programmed cell
      death 1 ligand 1(+)TGF-beta(+) macrophages and Foxp3(+) regulatory T cells in
      vivo. Neutralization of either TGF-beta or programmed cell death 1 ligand 1
      abrogated the protective effects of zymosan. Zymosan acted through TLR2 as well
      as ERK and p38 MAPK to induce macrophage secretion of TGF-beta and promotion of
      Foxp3(+) regulatory T cells in vitro and in vivo.

PMID- 20675591
TI  - ERK is integral to the IFN-gamma-mediated activation of STAT1, the expression of
      key genes implicated in atherosclerosis, and the uptake of modified lipoproteins
      by human macrophages.
AB  - The proinflammatory cytokine IFN-gamma is a master regulator of atherosclerosis
      and mediates its cellular actions mainly through STAT1. Unfortunately, the impact
      of other IFN-gamma inducible pathways on STAT1 activation and the regulation of
      downstream responses associated with atherosclerosis in human macrophages are
      poorly understood and were therefore investigated. In this study, we demonstrate
      that the IFN-gamma-mediated phosphorylation of STAT1 on Ser(727), crucial for its
      maximal activity, was attenuated in human macrophages by pharmacological
      inhibition of ERK. In these cells, IFN-gamma induced changes in the expression of
      several key genes implicated in atherosclerosis, such as MCP-1, through an ERK
      dependent mechanism. Additionally, the IFN-gamma-induced activity of STAT1
      responsive promoters was attenuated by transfection of dominant-negative forms of
      ERK and other key components of this pathway. Furthermore, the IFN-gamma-induced
      uptake of acetylated and oxidized low-density lipoprotein by human macrophages
      was attenuated by pharmacological inhibition or RNA interference-mediated
      knockdown of ERK. These studies suggest a critical role for ERK signaling in the
      IFN-gamma-mediated changes in macrophage cholesterol homeostasis and gene
      expression during atherosclerosis.

PMID- 20675592
TI  - Tumor cell-released TLR4 ligands stimulate Gr-1+CD11b+F4/80+ cells to induce
      apoptosis of activated T cells.
AB  - Gr-1(+)CD11b(+)F4/80(+) cells play important roles in tumor development and have
      a negative effect on tumor immunotherapy. So far, the mechanisms underlying the
      regulation of their immunosuppressive phenotype by classical and alternative
      macrophage activation stimuli are not well elucidated. In this study, we found
      that molecules from necrotic tumor cells (NTC-Ms) stimulated Gr
      1(+)CD11b(+)F4/80(+) cells to induce apoptosis of activated T cells but not
      nonstimulated T cells. The apoptosis-inducing capacity was determined by higher
      expression levels of arginase I and IL-10 relative to those of NO synthase 2 and
      IL-12 in Gr-1(+)CD11b(+)F4/80(+) cells, which were induced by NTC-Ms through TLR4
      signaling. The apoptosis-inducing capacity of NTC-Ms-stimulated Gr
      1(+)CD11b(+)F4/80(+) cells could be enhanced by IL-10. IFN-gamma may reduce the
      apoptosis-inducing capacity of Gr-1(+)CD11b(+)F4/80(+) cells only if their
      response to IFN-gamma was not attenuated. However, the potential of Gr
      1(+)CD11b(+)F4/80(+) cells to express IL-12 in response to IFN-gamma could be
      attenuated by tumor, partially due to the existence of active STAT3 in Gr
      1(+)CD11b(+)F4/80(+) cells and NTC-Ms from tumor. In this situation, IFN-gamma
      could not effectively reduce the apoptosis-inducing capacity of Gr
      1(+)CD11b(+)F4/80(+) cells. Tumor immunotherapy with 4-1BBL/soluble programmed
      death-1 may significantly reduce, but not abolish the apoptosis-inducing capacity
      of Gr-1(+)CD11b(+)F4/80(+) cells in local microenvironment. Blockade of TLR4
      signaling could further reduce the apoptosis-inducing capacity of Gr
      1(+)CD11b(+)F4/80(+) cells and enhance the suppressive effect of 4-1BBL/soluble
      form of programmed death-1 on tumor growth. These findings indicate the
      relationship of distinct signaling pathways with apoptosis-inducing capacity of
      Gr-1(+)CD11b(+)F4/80(+) cells and emphasize the importance of blocking TLR4
      signaling to prevent the induction of T cell apoptosis by Gr-1(+)CD11b(+)F4/80(+)
      cells.

PMID- 20675593
TI  - Escherichia coli K1 promotes the ligation of CD47 with thrombospondin-1 to
      prevent the maturation of dendritic cells in the pathogenesis of neonatal
      meningitis.
AB  - Dendritic cells (DCs) are professional APCs providing a critical link between
      adaptive and innate immune responses. Our previous studies have shown that
      Escherichia coli K1 internalization of myeloid DCs suppressed the maturation of
      the cells for which outer membrane protein A (OmpA) expression is essential. In
      this study, we demonstrate that infection of DCs with OmpA(+) E. coli
      significantly upregulates the expression of CD47, an integrin-associated protein,
      and its natural ligand thrombospondin 1 (TSP-1). Pretreatment of DCs with anti
      CD47 blocking Ab or knocking down the expression of CD47 or TSP-1, but not signal
      regulatory protein alpha by small interfering RNA, abrogated the suppressive
      effect of E. coli K1. Ligation of CD47 with a mAb prevented the maturation and
      cytokine production by DCs upon stimulation with LPS similar to the inhibitory
      effect induced by OmpA(+) E. coli. In agreement with the in vitro studies,
      suppression of CD47 or TSP-1 expression in newborn mice by a novel in vivo small
      interfering RNA technique protected the animals against E. coli K1 meningitis.
      Reconstitution of CD47 knockdown mice with CD47(+) DCs renders the animals
      susceptible to meningitis by E. coli K1, substantiating the role of CD47
      expression in DCs for the occurrence of meningitis. Our results demonstrate a
      role for CD47 for the first time in bacterial pathogenesis and may be a novel
      target for designing preventive approaches for E. coli K1 meningitis.

PMID- 20675594
TI  - TLR and B cell receptor signals to B cells differentially program primary and
      memory Th1 responses to Salmonella enterica.
AB  - Protective Th1 responses to Salmonella enterica do not develop in the absence of
      B cells. Using chimeric mice, we dissect the early (innate) and late (cognate)
      contributions of B cells to Th programming. B cell-intrinsic MyD88 signaling is
      required for primary effector Th1 development, whereas Ag-specific BCR-mediated
      Ag presentation is necessary for the development of memory Th1 populations.
      Programming of the primary T cell response is BCR/B cell MHC II independent, but
      requires MyD88-dependent secretion of cytokines by B cells. Chimeras in which B
      cells lack IFN-gamma or IL-6 genes make impaired Th1 or Th17 responses to
      Salmonella.

PMID- 20675596
TI  - Mast cells contribute to the mucosal adjuvant effect of CTA1-DD after IgG-complex
      formation.
AB  - Mast cell activation is one of the most dramatic immune-mediated responses the
      body can encounter. In the worst scenario (i.e., anaphylaxis), this response is
      fatal. However, the importance of mast cells as initiators and effectors of both
      innate and adaptive immunity in healthy individuals has recently been
      appreciated. It was reported that mast cell activation can be used as an adjuvant
      to promote Ag-specific humoral immune responses upon vaccination. In this study,
      we have used a clinically relevant mucosal adjuvant, cholera toxin A1 subunit
      (CTA1)-DD, which is a fusion protein composed of CTA1, the ADP-ribosylating part
      of cholera toxin, and DD, two Ig-binding domains derived from Staphylococcus
      aureus protein A. CTA1-DD in combination with polyclonal IgG induced
      degranulation and production of TNF-alpha from mouse mast cells. Furthermore,
      CTA1-DD and polyclonal IgG complex induced mast cell degranulation in mouse skin
      tissue and nasal mucosa. We also found that intranasal immunization with hapten
      (4-hydroxy-3-nitrophenyl) acetyl (NP) coupled to chicken gammaglobulin admixed
      with CTA1-DD complexed with polyclonal IgG greatly enhanced serum IgG anti-NP Ab
      responses and stimulated higher numbers of NP-specific plasma cells in the bone
      marrow as compared with that observed in mice immunized with NP-chicken
      gammaglobulin with CTA1-DD alone. This CTA1-DD/IgG complex-mediated enhancement
      was mast cell dependent because it was absent in mast cell-deficient Kit(W-sh/W
      sh) mice. In conclusion, our data suggest that a clinically relevant adjuvant,
      CTA1-DD, exerts additional augmenting effects through activation of mucosal mast
      cells, clearly demonstrating that mast cells could be further exploited for
      improving the efficacy of mucosal vaccines.

PMID- 20675595
TI  - Intralesional delivery of dendritic cells engineered to express T-bet promotes
      protective type 1 immunity and the normalization of the tumor microenvironment.
AB  - T-bet (Tbx21), a T-box transcription factor, has been previously identified as a
      master regulator of type 1 T cell polarization. We have also recently shown that
      the genetic engineering of human dendritic cells (DCs) to express human T-bet
      cDNA yields type 1-polarizing APCs in vitro (1). In the present study, murine
      CD11c(+) DCs were transduced with a recombinant adenovirus encoding full-length
      murine T-bets (DC.mTbets) and analyzed for their immunomodulatory functions in
      vitro and in vivo. Within the range of markers analyzed, DC.mTbets exhibited a
      control DC phenotype and were indistinguishable from control DCs in their ability
      to promote allogenic T cell proliferation in MLR in vitro. However, DC.mTbets
      were superior to control DCs in promoting Th1 and Tc1 responses in vitro via a
      mechanism requiring DC-T cell interaction or the close proximity of these two
      cell types and that can only partially be explained by the action of DC
      elaborated IL-12p70. When injected into day 7 s.c. CMS4 sarcoma lesions growing
      in syngenic BALB/c mice, DC.mTbets dramatically slowed tumor progression (versus
      control DCs) and extended overall survival via a mechanism dependent on both
      CD4(+) and CD8(+) T cells and, to a lesser extent, asialoGM1(+) NK cells.
      DC.mTbet-based therapy also promoted superior tumor-specific Tc1 responses in the
      spleens and tumor-draining lymph nodes of treated animals, and within the tumor
      microenvironment it inhibited the accumulation of CD11b(+)Gr1(+) myeloid-derived
      suppressor cells and normalized CD31(+) vascular structures. These findings
      support the potential translational utility of DC.Tbets as a therapeutic modality
      in the cancer setting.

PMID- 20675597
TI  - The complement inhibitors Crry and factor H are critical for preventing
      autologous complement activation on renal tubular epithelial cells.
AB  - Congenital and acquired deficiencies of complement regulatory proteins are
      associated with pathologic complement activation in several renal diseases. To
      elucidate the mechanisms by which renal tubular epithelial cells (TECs) control
      the complement system, we examined the expression of complement regulatory
      proteins by the cells. We found that Crry is the only membrane-bound complement
      regulator expressed by murine TECs, and its expression is concentrated on the
      basolateral surface. Consistent with the polarized localization of Crry, less
      complement activation was observed when the basolateral surface of TECs was
      exposed to serum than when the apical surface was exposed. Furthermore, greater
      complement activation occurred when the basolateral surface of TECs from Crry(-/
      )fB(-/-) mice was exposed to normal serum compared with TECs from wild-type mice.
      Complement activation on the apical and basolateral surfaces was also greater
      when factor H, an alternative pathway regulatory protein found in serum, was
      blocked from interacting with the cells. Finally, we injected Crry(-/-)fB(-/-)
      and Crry(+/+)fB(-/-) mice with purified factor B (an essential protein of the
      alternative pathway). Spontaneous complement activation was seen on the tubules
      of Crry(-/-)fB(-/-) mice after injection with factor B, and the mice developed
      acute tubular injury. These studies indicate that factor H and Crry regulate
      complement activation on the basolateral surface of TECs and that factor H
      regulates complement activation on the apical surface. However, congenital
      deficiency of Crry or reduced expression of the protein on the basolateral
      surface of injured cells permits spontaneous complement activation and tubular
      injury.

PMID- 20675599
TI  - Genetic evaluation of type traits in hypertrophic Piemontese cows.
AB  - The aim of this study was to estimate genetic parameters for type traits of
      hypertrophic Piemontese cows. Seven traditional type trait evaluations (70 to 100
      grid scores), 2 body measurements (cm), and 13 linear description traits (1 to 9
      grid scores) recorded on 21,757 Piemontese primiparous cows reared in 990 farms
      were used. Data were analyzed using a multiple-trait (22 traits) animal model
      with canonical transformation, accounting for a unique design matrix with the
      following effects: herd-year-classifier, days in milk, age at calving, and the
      genetic additive cow effect. Heritability estimates of traditional type
      evaluation traits were low for thorax, rump, feet and legs, and dairyness
      (<=0.10), intermediate for fleshiness and overall score evaluations (0.13 to
      0.15), and medium to high for body size (0.26). Genetic correlations of dairyness
      with all the other traditional type traits were low (from -0.14 to 0.16), those
      of feet and legs were moderate (0.19 to 0.44), and the remaining 5 traits were
      high (>=0.55), with an exception regarding fleshiness and body size (0.28).
      Medium-high heritability estimates were obtained for withers height (0.31) and
      trunk length (0.21), with a very high genetic correlation between these traits
      (0.97). The genetic correlations of body measurements with body size were also
      very high (about 0.96), high with thorax, rump, and overall score (0.47 to 0.59),
      and moderate with the other traditional type traits (0.04 to 0.27). Heritability
      estimates of all linear traits were moderate (0.09 to 0.15), with the exceptions
      of top line (0.07) and condition score (0.05). Genetic correlations between
      linear traits were generally low to moderate (from -0.11 to 0.44) with the only
      exceptions of the 6 fleshiness traits and body condition, which showed very high
      correlations (0.60 to 0.96). Moreover, skeletal traits as top line, bone
      thinness, and head scores presented moderate genetic correlations (0.51 to 0.65).
      Genetic correlations between linear traits and traditional type traits were
      consistent with the trend observed between type traits. In conclusion, body
      measurements seem to describe body size better than traditional evaluation or
      linear descriptors. The genetic correlations among type evaluation and linear
      description traits suggest the need for a reduction in the number of traits
      scored, particularly of those relating to muscular development.

PMID- 20675600
TI  - Changes of the activities of glycolytic and oxidative enzymes before and after
      slaughter in the longissimus muscle of Pietrain and Duroc pigs and a Duroc
      Pietrain crossbreed.
AB  - After slaughter of pigs, the pH of the meat decreases due to lactate accumulation
      within the tissue. In addition to calcium homeostasis, energy metabolism plays a
      key role during the muscle-to-meat transition, and it is interesting to know how
      specific enzymes of the glycolytic and oxidative pathways change during this
      process, especially in relation to the antemortem situation, and if there is an
      impact of these alterations on the meat quality characteristics. Therefore, in
      the present study samples of the LM from the pig genetic groups Pietrain (Pi),
      Duroc (Du), and a Du * Pi crossbreed population (DuPi) were collected 24 h before
      as well as 1 min, 40 min, and 12 h after slaughter, and the activities of the
      glycogen phosphorylase (GP), phosphofructokinase (PFK), lactate dehydrogenase
      (LDH), citrate synthase (CS), NADH-ubiquinone oxidoreductase (complex I), and
      cytochrome oxidase were analyzed. Additional investigations include carcass and
      meat quality characteristics as well as the microstructure of the LM. The Pi
      breed had greater (P < 0.05) carcass yield and lean meat values, but no
      differences (P > 0.05) of the meat quality traits could be determined between the
      investigated pig breeds. The Pi pigs exhibited a greater (P < 0.05) percentage of
      fast-twitch glycolytic and had smaller amounts (P < 0.05) of slow-twitch
      oxidative fibers in comparison with the Du pigs. The enzyme activities of the GP,
      PFK, and complex I increased (P < 0.05) immediately after slaughter (1 min
      postmortem) of the pigs and the activity of the LDH within 40 min postmortem.
      After 12 h, the GP, PFK, LDH, and complex I activities decreased to the amount of
      the preslaughter sample. No differences could be found with regard to the enzyme
      activities of the CS and cytochrome oxidase at all determination times.
      Considering the enzyme activities within the different breeds, the Pi pigs
      exhibited greater (P < 0.05) GP and PFK and the Du animals exhibited greater (P <
      0.05) CS and complex I activities. The study indicates that the glycolytic
      enzymes GP, PFK, and LDH as well as the complex I influence the muscle-to-meat
      transition process after slaughter of the animals without an impact on the muscle
      quality. The activities of the GP, PFK, CS, and complex I reflect the differences
      of the muscle fiber composition between the Pi and Du pigs.

PMID- 20675601
TI  - Efficacy of experimentally produced spray-dried plasma on infectivity of porcine
      circovirus type 2.
AB  - The value of incorporating spray-dried plasma (SDP) into the diet of weanling
      pigs to improve feed intake and growth performance has been well documented.
      However, limited work has been done to confirm that the spray-drying process
      eliminates all viral contaminates including porcine circovirus type 2 (PCV2). To
      determine the effect of spray-drying on PCV2 infectivity, colostrum-fed,
      crossbred, specific-pathogen-free (SPF) pigs were inoculated with PCV2
      contaminated SDP intraperitoneally (SDP-IP) or by oral gavage (SDP-OG),
      inoculated intraperitoneally with PCV2-positive plasma (POS), or left
      uninoculated (NEG). The plasma used for the experimentally produced SDP was
      collected from a SPF pig experimentally infected with a PCV2b isolate. Pigs in
      the NEG group remained seronegative, and PCV2 viremia was not detected. All pigs
      in the POS group became PCV2 viremic by 14 d postinoculation (DPI) and
      seroconverted by 28 DPI. In the SDP-IP group, all pigs became viremic by 35 DPI
      and seroconverted by 49 DPI. In the SDP-OG group, all animals became viremic by
      35 DPI and 2/3 pigs seroconverted by 35 DPI. There were no significant (P > 0.05)
      differences between anti-PCV2-IgG antibody sample-to-positive ratios among pigs
      in the POS, SDP-OG, or SDP-IP groups. This work provides direct evidence that the
      experimental spray-drying process used in this study was not effective in
      inactivating PCV2b in the plasma of a PCV2-infected pig based on a swine bioassay
      using PCV2-naive pigs. This work suggests that SDP sourced from pigs could
      represent a biosecurity risk for the industry.

PMID- 20675602
TI  - Differential effects of maternal undernutrition between days 1 and 90 of
      pregnancy on ewe and lamb performance and lamb parasitism in hill or lowland
      breeds.
AB  - This study examined the hypothesis that responses of Scottish Blackface (BF, a
      hill breed) and Suffolk (SUF, a lowland breed) ewes to undernutrition between d 1
      and 90 of pregnancy would differ. Over 2 consecutive breeding seasons, ewes (4
      pens/treatment; 15 to 20 ewes/pen) were artificially inseminated and from d 1 to
      90 after AI allocated to 0.75 (restricted; RES) or 1.0 (control; CON) energy
      requirements for ewe maintenance and fetal growth. From d 90 to term, all ewes
      were allocated feed to meet requirements for stage of pregnancy and expected
      litter size. On d 90, RES ewes had lighter BW (P = 0.001) and smaller BCS (P =
      0.019) than CON ewes. Plasma NEFA concentrations were greater in RES than CON
      ewes (P = 0.048) at d 60 of pregnancy. Pregnancy length was longer for RES than
      CON ewes (P = 0.003). Lambs from SUF-RES ewes had lighter birth weights than SUF
      CON lambs, but BF-RES lamb birth weights were not different from BF-CON lambs
      (interaction, P = 0.066). However, maternal undernutrition did not affect BW at
      weaning (P > 0.45). Between birth and 3 d of age, BF lambs maintained greater
      body temperatures (P < 0.001) and plasma concentrations of triiodothyronine (T3,
      P < 0.001) and thyroxine (P < 0.001) than SUF lambs. Lambs from RES ewes had
      greater concentrations of T3 (P = 0.026) than CON lambs, whereas these
      differences were greater between BF-RES and BF-CON lambs than between SUF-RES and
      SUF-CON lambs (interaction, P = 0.028). Maternal undernutrition did not affect
      lamb rectal temperature (P > 0.27). In yr 1 only, fewer lambs (P = 0.022) were
      reared to weaning by RES than CON ewes. Similarly, in yr 1 only, other strongyle
      fecal egg counts at weaning were greater in SUF-RES lambs than SUF-CON, BF-CON,
      or BF-RES lambs (interaction, P = 0.099). This experiment showed that lambs of a
      breed selected for lean tissue growth and normally maintained in a lowland
      environment were more affected by maternal undernutrition between d 1 and 90 of
      pregnancy than lambs of a hill breed managed in a more adverse environment.

PMID- 20675598
TI  - Regulation of dental enamel shape and hardness.
AB  - Epithelial-mesenchymal interactions guide tooth development through its early
      stages and establish the morphology of the dentin surface upon which enamel will
      be deposited. Starting with the onset of amelogenesis beneath the future cusp
      tips, the shape of the enamel layer covering the crown is determined by five
      growth parameters: the (1) appositional growth rate, (2) duration of appositional
      growth (at the cusp tip), (3) ameloblast extension rate, (4) duration of
      ameloblast extension, and (5) spreading rate of appositional termination.
      Appositional growth occurs at a mineralization front along the ameloblast distal
      membrane in which amorphous calcium phosphate (ACP) ribbons form and lengthen.
      The ACP ribbons convert into hydroxyapatite crystallites as the ribbons elongate.
      Appositional growth involves a secretory cycle that is reflected in a series of
      incremental lines. A potentially important function of enamel proteins is to
      ensure alignment of successive mineral increments on the tips of enamel ribbons
      deposited in the previous cycle, causing the crystallites to lengthen with each
      cycle. Enamel hardens in a maturation process that involves mineral deposition
      onto the sides of existing crystallites until they interlock with adjacent
      crystallites. Neutralization of acidity generated by hydroxyapatite formation is
      a key part of the mechanism. Here we review the growth parameters that determine
      the shape of the enamel crown as well as the mechanisms of enamel appositional
      growth and maturation.

PMID- 20675603
TI  - Enhancement technology improves palatability of normal and callipyge lambs.
AB  - The objective of this research was to determine if BPI Processing Technology
      (BPT) improved palatability of normal (NN) and callipyge (CN) lamb meat and to
      determine the mechanism by which palatability was improved. Ten ewe and 10 wether
      lambs of each phenotype were slaughtered, and carcass traits were assessed by a
      trained evaluator. The LM was removed at 2 d postmortem. Alternating sides served
      as controls (CON) or were treated with BPT. Muscles designated BPT were injected
      to a target 120% by weight with a patented solution containing water, ammonium
      hydroxide, carbon monoxide, and salt. Muscle pH, cooking loss, Warner-Bratzler
      shear force (WBS), sarcomere length, cooked moisture retention, and desmin
      degradation were measured. A trained sensory panel and a take-home consumer panel
      evaluated LM chops. Callipyge had a heavier BW and HCW, less adjusted fat
      thickness, reduced yield grades, and greater conformation scores than NN (P <
      0.05). For LM, NN had shorter sarcomeres, smaller WBS values, greater juiciness
      ratings, more off-flavors, reduced consumer ratings for raw characteristics (like
      of portion size, like of color, like of leanness, overall like of appearance) and
      greater consumer ratings for eating characteristics (like of juiciness, like of
      flavor) than CN (P < 0.05). For LM, BPT had greater cooked moisture retention,
      smaller WBS values, greater juiciness ratings, less off-flavors, and greater
      consumer ratings for raw characteristics (like of portion size, like of color,
      overall like of appearance) and eating characteristics (like of juiciness, like
      of flavor) than CON (P < 0.05). Significant phenotype * treatment interactions
      occurred for LM muscle pH, desmin degradation, tenderness, consumer like of
      texture/tenderness, and consumer overall like of eating quality (P < 0.05). For
      LM, BPT increased muscle pH more for NN than CN (P < 0.01) and increased desmin
      degradation for NN but decreased desmin degradation for CN (P < 0.01). The BPT
      enhancement improved LM tenderness ratings for CN more than NN (P < 0.05). For
      consumer like of texture/tenderness, BPT improved ratings for CN more than NN (P
      < 0.01). For consumer overall like of eating quality, BPT improved ratings for CN
      more than NN (P < 0.05). In summary, BPT had little to no effect on sarcomere
      length and desmin degradation, but improved palatability of NN and CN lamb by
      increasing cooked moisture retention, improving consumer acceptability of CN to
      near-normal levels.

PMID- 20675604
TI  - An application of change-point recursive models to the relationship between
      litter size and number of stillborns in pigs.
AB  - We developed and implemented change-point recursive models and compared them with
      a linear recursive model and a standard mixed model (SMM), in the scope of the
      relationship between litter size (LS) and number of stillborns (NSB) in pigs. The
      proposed approach allows us to estimate the point of change in multiple-segment
      modeling of a nonlinear relationship between phenotypes. We applied the procedure
      to a data set provided by a commercial Large White selection nucleus. The data
      file consisted of LS and NSB records of 4,462 parities. The results of the
      analysis clearly identified the location of the change points between different
      structural regression coefficients. The magnitude of these coefficients increased
      with LS, indicating an increasing incidence of LS on the NSB ratio. However,
      posterior distributions of correlations were similar across subpopulations
      (defined by the change points on LS), except for those between residuals. The
      heritability estimates of NSB did not present differences between recursive
      models. Nevertheless, these heritabilities were greater than those obtained for
      SMM (0.05) with a posterior probability of 85%. These results suggest a nonlinear
      relationship between LS and NSB, which supports the adequacy of a change-point
      recursive model for its analysis. Furthermore, the results from model comparisons
      support the use of recursive models. However, the adequacy of the different
      recursive models depended on the criteria used: the linear recursive model was
      preferred on account of its smallest deviance value, whereas nonlinear recursive
      models provided a better fit and predictive ability based on the cross-validation
      approach.

PMID- 20675605
TI  - Efficacy of different commercial phytase enzymes and development of an available
      phosphorus release curve for Escherichia coli-derived phytases in nursery pigs.
AB  - In 2 experiments, a total of 184 pigs (PIC, initial BW of 10.3 and 9.7 kg for
      Exp. 1 and 2, respectively) were used to develop an available P (aP) release
      curve for commercially available Escherichia coli-derived phytases. In both
      experiments, pigs were fed a corn-soybean meal basal diet (0.06% aP) and 2 diets
      with added inorganic P (iP) from monocalcium phosphate (Exp. 1: 0.075 and 0.15%
      aP; Exp. 2: 0.07 and 0.14% aP) to develop a standard curve. In Exp. 1, 100, 175,
      250, or 500 phytase units (FTU)/kg of OptiPhos 2000 or 200, 350, 500, or 1,000
      FTU/kg of Phyzyme XP were added to the basal diet. In Exp. 2, 250, 500, 750, or
      1,000 FTU/kg of OptiPhos 2000; 500, 1,000, or 1,500 FTU/kg of Phyzyme XP; or
      1,850 or 3,700 FTU/kg of Ronozyme P were added to the basal diet. One FTU was
      defined as the amount of enzyme required to release 1 umol of iP per minute from
      sodium phytate at 37 degrees C. For all phytase products, the manufacturer
      guaranteed phytase activities were used in diet formulation. All diets were
      analyzed for phytase activity using both the Phytex and AOAC methods. Pigs were
      blocked by sex and BW and allotted to individual pens with 8 pens per treatment.
      Pigs were killed on d 21, and fibulas were collected and analyzed for bone ash.
      In both experiments, increasing iP improved (linear, P < 0.01) G:F and percentage
      bone ash. Pigs fed increasing OptiPhos had improved (Exp. 1: linear, P < 0.001;
      Exp. 2: quadratic, P < 0.001) percentage bone ash, as did pigs fed increasing
      Phyzyme XP (linear, P < 0.001). In Exp. 2, increasing Ronozyme P improved
      (quadratic, P < 0.01) percentage bone ash. Using analyzed values from the AOAC
      method and percentage bone ash as the response variable, an aP release curve was
      developed for up to 1,000 FTU/kg of E. coli-derived phytases (OptiPhos 2000 and
      Phyzyme XP) in P-deficient diets. The prediction equation was Y = 
      0.000000125X(2) + 0.000236X + 0.016, where Y = aP release (%) and X = analyzed
      phytase (FTU/kg) in the diet.

PMID- 20675606
TI  - Metabolizable energy content of refined glycerin and its effects on growth
      performance and carcass and pork quality characteristics of finishing pigs.
AB  - Two studies were conducted with refined glycerin (97.7 and 97.5% glycerin for
      studies I and II, respectively) to determine ME content and effects on growth
      performance and carcass and pork quality measures of finishing pigs. An energy
      balance study using 24 barrows (21.5 +/- 0.6 kg initial BW) determined the
      apparent ME content of glycerin using a generalized randomized block design with
      2 dietary treatments: 1) control (99.85% corn + vitamins and minerals) and 2)
      glycerin (30% of corn in the control diet replaced with glycerin). A 7-d
      adaptation was followed by a 5-d collection period for feces and urine. The
      energy content of diets, feces, and urine was determined by bomb calorimetry. The
      DE of the glycerin diet was greater (P < 0.01) than that of the control diet
      (4,298 vs. 3,902 kcal/kg of DM); however, the ME content of the 2 diets was
      similar (3,820 vs. 3,723 kcal/kg of DM). The ME of refined glycerin (estimated by
      difference) was 3,584 kcal/kg of DM. A growth study was conducted with 128 gilts
      housed in groups of 4 and reared from 92.5 +/- 0.24 kg of BW for a 28-d period,
      using a split-plot design with a 4 * 2 factorial arrangement of treatments: 1)
      dietary glycerin level (0, 5, 10, and 15%) and 2) preslaughter handling (gentle
      vs. intense). The handling treatment was included to simulate the range in
      handling intensities that are likely to be experienced in practice. At the end of
      the 28-d period, one-half of the pens on study were slaughtered and used for
      carcass and pork quality evaluation with 2 pigs from each pen being subjected to
      each of the preslaughter handling treatments. There were no interactions (P >
      0.05) between dietary glycerin and preslaughter handling treatment. Dietary
      glycerin had no effect (P > 0.05) on growth performance, carcass measures, or
      meat quality. There were no differences (P > 0.05) between the gentle and intense
      handling treatments for carcass or pork quality measures. In conclusion, feeding
      glycerin to finishing pigs at up to 15% of the diet had no negative effect on
      growth performance or carcass and pork quality characteristics.

PMID- 20675607
TI  - Factors associated with sow stayability in 6 genotypes.
AB  - The purpose of this study was to determine the association of production factors
      with stayability to parity 4 (STAY4) under controlled experimental conditions.
      Data were from 2,293 female pigs, sampled from 6 genetic lines that were entered
      into the National Pork Producers Council Maternal Line National Genetic
      Evaluation Program. Genetic lines evaluated included Newsham (NH), National Swine
      Registry (NSR), American Diamond Swine Genetics (ADSG), Danbred (DAN), and 2
      Dekalb-Monsanto lines (DK44 and GPK347). Stepwise logistic regression was
      utilized in the analysis of STAY4. All effects were nested within genetic line.
      Categorical effects in the model were arrival date to the wean-to-finish unit
      (entry date) and breed-gestation-farrowing facility (farm). Continuous effects in
      the model were gilt backfat, LM depth, ADG, age at puberty, age at first
      farrowing, and traits recorded before the last litter of the sow (prefarrow
      backfat, number born alive, number weaned, litter weaning weight, lactation feed
      intake, lactation backfat loss, and lactation length). Factors significant for
      STAY4 included farm, entry date, age at first farrowing, ADG, gilt backfat, and
      lactation before removal effects, as well as feed intake, number born alive, and
      lactation length. Age at first farrowing and lactation feed intake affected all
      genetic lines. Regression coefficients for STAY4 on age at first farrowing were 
      0.014, -0.022, -0.017, -0.016, -0.011, and -0.021 (all P < 0.05), respectively,
      for NH, NSR, ADSG, DK44, GPK347, and DAN genetic lines. Regression coefficients
      for STAY4 on lactation feed intake were 0.043, 0.049, 0.051, 0.061, 0.120, and
      0.097 (all P < 0.05), respectively, for NH, NSR, ADSG, DK44, GPK347, and DAN
      females. Age at puberty, age at first farrowing, and lactation feed intake had
      the greatest effect on STAY4.

PMID- 20675608
TI  - Segmentation and thickness measurement of glomerular basement membranes from
      electron microscopy images.
AB  - An algorithm for segmentation and thickness measurement of the glomerular
      basement membranes (GBM) in electron microscopy kidney images is presented.
      Differences in intensities and variations between GBM and other components in the
      image are employed. Regions of extreme intensities such as the black area of
      blood cells and white areas of urinary spaces are pre-excluded. Areas of sharp
      edges are either at the GBM borders or unrelated to GBM regions. These non-GBM
      sharp edges, along with the pre-excluded regions, are used as barriers limiting
      the size of the fitting circles centered at a location in the image domain to
      form a two-dimensional function, proportional to the radius of the largest
      fitting circle, at the location. A local peak in the radius function corresponds
      to the largest circle in the local area. The set of the combined peaks in two
      perpendicular directions is calculated before a thinning procedure is applied.
      After removing the unwanted branches, a centerline of the GBM is produced. The
      segmentation of the GBM is then straightforward from expanding each point in the
      centerline to a circle of radius defined by the radius function. The average of
      the diameters of the circles gives the average GBM thickness. Results of the real
      GBM images are provided. Visual comparisons from the superimposed GBM boundaries
      show that the algorithm provides accurate GBM segmentation. The evaluations of
      the average GBM thicknesses are also compared to those from the manual tracing
      method.

PMID- 20675609
TI  - A longitudinal study of kidney structure and function in adults.

PMID- 20675610
TI  - The mutation c.1196_1202dup7bp (p.Ser402X) in the SLC12A3 gene clusters in
      Italian Gitelman syndrome patients and reflects the presence of a common
      ancestor.
AB  - BACKGROUND: Inactivating mutations in the SLC12A3 gene are the main cause of
      Gitelman's syndrome (GS), a renal tubular disorder inherited as an autosomal
      recessive trait. In our cohort of patients, we identified 11 probands from 11
      apparently unrelated Italian families that carry the c.1196_1202dup7bp mutation,
      which appears to be more frequent than other mutations in Italian GS patients.
      Therefore, we characterized in greater detail the SLC12A3 locus and its vicinity
      in those patients that carry this mutation in order to detect a possible shared
      haplotype. Three further probands characterized in France, carrying the same
      mutation, were also included in this study. METHODS: Sequence or fragment
      analyses were carried out to investigate seven intragenic polymorphisms
      (rs3217425, rs3816119, rs2304483, rs2278490, rs2278489, rs2289116 and rs2289115)
      that flank the mutation, as well as two extragenic markers, D16S3071 and
      D16S3057, flanking the SLC12A3 locus in the 5' and 3' termini, respectively.
      RESULTS: A shared haplotype co-segregates with the mutation both in Italian and
      French probands. Moreover, all the Italian families originate from a restricted
      area of Italy. Likewise, the French probands come from an area of France close to
      the north of Italy. CONCLUSION: It is likely that the c.1196_1202dup7bp mutation
      in the SLC12A3 gene reflects the presence of a common ancestor in an area
      covering the northern-central part of Italy and eastern France. A modified
      genotyping strategy for GS patients originating from this area has to be
      considered.

PMID- 20675611
TI  - Detection of androgen receptor mutations in circulating tumor cells: highlights
      of the long road to clinical qualification.

PMID- 20675612
TI  - Response to Cembrowski et al. regarding "Could susceptibility to low hematocrit
      interference have compromised the results of the NICE-SUGAR trial?".

PMID- 20675613
TI  - Complex assembly and metabolic profiling of Arabidopsis thaliana plants
      overexpressing vitamin B6 biosynthesis proteins.
AB  - In plants, vitamin B6 biosynthesis requires the activity of PDX1 and PDX2
      proteins. Arabidopsis thaliana encodes for three PDX1 proteins, named PDX1.1,
      1.2, and 1.3, but only one PDX2. Here, we show in planta complex assembly of PDX
      proteins, based on split-YFP and FPLC assays, and can demonstrate their presence
      in higher complexes of around 750 kDa. Metabolic profiling of plants ectopically
      expressing the different PDX proteins indicates a negative influence of PDX1.2 on
      vitamin B6 biosynthesis and a correlation between aberrant vitamin B6 content,
      PDX1 gene expression, and light sensitivity specifically for PDX1.3. These
      findings provide first insights into in planta vitamin B6 synthase complex
      assembly and new information on how the different PDX proteins affect plant
      metabolism.

PMID- 20675614
TI  - The increasing use of theory in social gerontology: 1990-2004.
AB  - OBJECTIVES: To determine how often theory is used in published research in social
      gerontology, compare theory use over a 10-year period (1990-1994 to 2000-2004),
      and identify the theories most frequently used in social gerontology research.
      METHODS: Systematic review of articles published in eight leading journals from
      2000 to 2004 (N = 1,046) and comparison with a review conducted 10 years earlier.
      RESULTS: Theory was mentioned in 39% of articles published from 2000 to 2004,
      representing a 12% increase in the use of theory over 10 years. This increase was
      driven by theories outside the core sociology of aging theories identified by
      Bengtson, V. L., Burgess, E. O., and Parrott, T. M. (1997). Theory, explanation,
      and a third generation of theoretical development in social gerontology. Journal
      of Gerontology: Social Sciences, 52B, S72-S88. The five most frequently used
      theories included the life course perspective, life-span developmental theories,
      role theory, exchange theory, and person-environment theory/ecological theories
      of aging. Commonly used models included stress process/stress and coping models,
      successful aging models, the Andersen behavioral model of health services use,
      models of control/self-efficacy/mastery, and disablement process models.
      DISCUSSION: Theory use in social gerontology increased between 1990 and 2004,
      with a shift toward theories that cross disciplines. However, the majority of
      research in social gerontology continues to be atheoretical. Models are widely
      used as a supplement to or substitute for theory. Many of these models are
      currently being debated and elaborated, and over time, they may emerge as
      important theoretical contributions to social gerontology.

PMID- 20675615
TI  - Forgiveness and the need to belong.
AB  - People who experience a strong need to belong might be particularly inclined to
      forgive wrongdoings to preserve social bonds. Three studies that utilized
      different methods and measures of forgiveness consistently demonstrated this is
      not the case. The authors found that individuals high in the need to belong
      report practicing forgiveness with less frequency and value it no more than those
      low in the need to belong (Study 1). In Study 2, they found that satisfying the
      need to belong led participants to express greater willingness to forgive
      hypothetical offenses compared to participants in a control group. Finally, in
      Study 3, the authors linked the need to belong to forgiveness of specific
      transgressions and found that this negative relationship was mediated by offense
      related anger and perceptions of offense severity. These findings suggest that
      needing to belong paradoxically interferes with forgiveness, even though
      forgiving could promote the satisfaction of belongingness needs following
      transgressions.

PMID- 20675616
TI  - The genomic distribution and local context of coincident SNPs in human and
      chimpanzee.
AB  - We have previously shown that there is an excess of sites that are polymorphic at
      orthologous positions in humans and chimpanzees and that this is most likely due
      to cryptic variation in the mutation rate. We showed that this might be a
      consequence of complex context effects since we found significant heterogeneity
      in triplet frequencies around coincident single nucleotide polymorphism (SNP)
      sites. Here, we show that the heterogeneity in triplet frequencies is not
      specifically associated with coincident SNPs but is instead driven by base
      composition bias around CpG dinucleotides. As a result, we suggest that cryptic
      variation in the mutation rate is truly cryptic, in the sense that the mutation
      rate does not appear to depend on any specific primary sequence context.
      Furthermore, we propose that the patterns around CpG dinucleotides are driven by
      the mutability of CpG dinucleotides in different DNA contexts. We also show that
      the genomic distribution of coincident SNPs is nonuniform and that there are some
      subtle differences between the distributions of single and coincident SNPs.
      Furthermore, we identify regions that contain high numbers of coincident SNPs and
      suggest that one in particular, a region containing the gene PRIM2, may be under
      balancing selection.

PMID- 20675617
TI  - A new framework for studying the isochore evolution: estimation of the
      equilibrium GC content based on the temporal mutation rate model.
AB  - Isochore is the genome-wide mosaic structure in guanine-cytosine (GC) content.
      The origin of isochores is thought to have emerged in the ancestral amniote
      genome, and the GC-rich isochore is eroded in the mammalian lineages. However,
      there are many enigmas in the isochore evolution: 1) although all the mammalians,
      birds, and even reptiles, which are clearly polyphyletic, have isochore, opossum
      and platypus lack GC-rich and GC-poor isochore classes; 2) although the isochore
      is predicted to vanish according to a fairly robust theory, a completely opposite
      conclusion was led in some mammalian lineages; and 3) the major three hypotheses
      on the isochore evolution cannot explain observed evidences without flaws. So far
      compositional evolution has been studied under the assumption that per base pair
      rate of GC-->AT (u) and AT-->GC (v) mutations are temporally constant (the
      constant model). With this model alone, however, it is difficult to explain the
      isochore evolution. We propose a simple model for compositional evolution based
      on the temporal per base pair rate of mutations (the variable model). In this
      model, rates u and v vary depending on temporal GC contents. Mathematically, the
      variable model is an expansion of the constant model. By using high-density human
      single nucleotide polymorphism data, we compared the variable model with the
      constant model. Although the variable model gave consistent results with the
      constant model, it can potentially describe the complicated isochore evolution,
      which the constant model cannot explain. The versatile characteristics of the
      variable model may shed new light on the mysterious isochore evolution.

PMID- 20675618
TI  - Two functionally distinct isoforms of TL1A (TNFSF15) generated by differential
      ectodomain shedding.
AB  - Tumor necrosis factor-like cytokine 1A (TL1A) is expressed in endothelial cells
      and contributes to T-cell activation, via an extracellular fragment TL1A(L72
      L251), generated by ectodomain shedding. Fragments of TL1A, referred to as
      vascular endothelial growth inhibitor, were found to induce growth arrest and
      apoptosis in endothelial cells; however, the underlying mechanisms remained
      obscure. Here, we show that full-length TL1A is the major detectable gene product
      in both human umbilical vein endothelial cells and circulating endothelial
      progenitor cells. TL1A expression was significantly enhanced in senescent
      circulating endothelial progenitor cells, and knockdown of TL1A partially
      reverted senescence. TL1A overexpression induced premature senescence in both
      circulating endothelial progenitor cells and human umbilical vein endothelial
      cells. We also identified a novel extracellular fragment of TL1A, TL1A(V84-L251),
      resulting from differential ectodomain shedding, which induced growth arrest and
      apoptosis in human umbilical vein endothelial cells. These findings suggest that
      TL1A is involved in the regulation of endothelial cell senescence, via a novel
      fragment produced by differential ectodomain shedding.

PMID- 20675621
TI  - Empowerment interventions for older adults.
AB  - There has been much discussion regarding the need to empower older adults to make
      informed health decisions and to test interventions targeting empowerment to
      promote health among older adults. It has been suggested that an empowerment
      approach may nurture an older adult's participation in health care decisions and
      promote positive health outcomes. The purpose of this article is to report the
      findings of a critical review of published empowerment intervention studies with
      community-dwelling older adults. A descriptive literature review was conducted to
      examine how empowerment is conceptualized across interventions, the guiding
      theoretical frameworks, the outcomes measured, as well as the health outcomes of
      these interventions. Based on the findings from this review, recommendations for
      future empowerment intervention research with older adults as well as
      implications for practice are proposed.

PMID- 20675619
TI  - Chronic medical conditions and the sex-based disparity in disability: the
      Cardiovascular Health Study.
AB  - BACKGROUND: Older women experience disability more commonly than their male
      peers. This disparity may be due, in part, to sex-based differences in the
      prevalence or the disabling effects of common medical conditions. The objectives
      of this analysis were to (a) quantify the extent to which excess disability in
      women is explained by higher prevalence of selected medical conditions and (b)
      evaluate whether the same conditions have differing effects on disability in men
      and women. METHODS: We analyzed cross-sectional data from 5,888 community
      dwelling older men and women. Disability was defined as difficulty with greater
      than or equal to one activity of daily living. Thirteen medical conditions were
      assessed by self-report, testing, or record review. RESULTS: Controlling for age,
      race, education, and marital status, women were more likely to experience
      disability (odds ratio = 1.70, 95% confidence interval = 1.36-2.11). Higher
      prevalence of arthritis and obesity in women explained 30.2% and 12.9%,
      respectively, of the sex-based difference in disability rates, whereas male
      prevalent diseases like vascular conditions and emphysema narrowed the disability
      gap. Women with arthritis, hearing problems, coronary artery disease, congestive
      heart failure, stroke, and claudication were more likely to exhibit disability
      compared with men with the same conditions (p < .001). CONCLUSIONS: Efforts to
      lessen sex-based inequality in disability should focus on reducing the prevalence
      of arthritis and obesity. Future generations may see greater functional disparity
      if rates of vascular disease and emphysema rise among women. Several conditions
      were more often associated with disability in women, suggesting additional sex
      based differences in the disablement process.

PMID- 20675620
TI  - Effects of testosterone administration on nocturnal cortisol secretion in healthy
      older men.
AB  - In animal studies, testosterone decreases, whereas estrogen increases, cortisol
      production. In one clinical study, short-term testosterone replacement attenuated
      corticotrophin-releasing hormone-stimulated cortisol secretion during leuprolide
      induced hypogonadism in young men. The effects of longer term testosterone
      treatment on spontaneous cortisol secretion in younger or older men are unknown.
      In a randomized, double-masked placebo-controlled study, we assessed the effects
      of testosterone supplementation (100 mg intramuscular every 2 week) for 26 weeks
      on nocturnal cortisol secretory dynamics in healthy older men. Testosterone
      administration increased early morning serum concentrations of free testosterone
      by 34%, decreased sex hormone-binding globulin by 20%, and did not alter early
      morning concentrations of cortisol-binding globulin or cortisol compared with
      placebo treatment. Testosterone did not significantly alter nocturnal mean and
      integrated cortisol concentrations, cortisol burst frequency, mass/burst, basal
      secretion, pulsatile cortisol production rate, pattern regularity, or approximate
      entropy. We conclude that low-dose testosterone supplementation for 26 weeks does
      not affect spontaneous nocturnal cortisol secretion in healthy older men.

PMID- 20675622
TI  - Surveillance turns to wildlife.

PMID- 20675623
TI  - More cases of 'bleeding calf syndrome' diagnosed across Scotland.

PMID- 20675625
TI  - Infection with bluetongue virus serotype 8 in Sweden in 2008.
AB  - On September 6, 2008, bluetongue was detected for the first time in Sweden.
      Intensified active surveillance in cattle and vector surveillance, prompted by
      the situation in northern Europe, preceded the detection. A vaccination campaign
      and intensive surveillance activities were initiated nationally, but with a focus
      on the southern part of the country. Measures included both active and passive
      surveillance by serology and PCR in ruminants, along with vector surveillance.
      The investigations revealed that the infection occurred over a large area of
      southern Sweden during September and October 2008, despite comparatively low
      vector activity, an apparently low viral load and no clinical disease.
      Transplacental infection was detected in one case.

PMID- 20675624
TI  - Effect of delivery method on the efficacy of Salmonella vaccination in chickens.
AB  - To investigate whether the efficacy of live vaccines is influenced by the mode of
      vaccine delivery, a widely-used UK live commercial Salmonella Enteritidis vaccine
      was delivered to pullet chicks either by spray, in drinking water, or in
      combination with a bivalent vaccine containing inactivated Salmonella Enteritidis
      and Salmonella Typhimurium. The birds were subsequently challenged with 10(2) or
      10(8) colony-forming units (cfu) of Salmonella Enteritidis through drinking water
      at either six or 20 weeks of age. Ten days after the challenge, the birds were
      euthanased and their caecal contents cultured for Salmonella. All of the
      vaccinated groups contained fewer Salmonella Enteritidis-positive birds than the
      unvaccinated groups. The 'spray-vaccinated' group contained significantly fewer
      Salmonella Enteritidis-positive birds than the 'water-vaccinated' group after
      challenge with 10(8) cfu at 20 weeks. However, there was little or no difference
      at the other challenge time points between the groups that received vaccine
      through different modes of delivery.

PMID- 20675627
TI  - Prevalence of a host-adapted group B Salmonella enterica in harbour porpoises
      (Phocoena phocoena) from the south-west coast of England.
AB  - A monophasic group B Salmonella enterica 4,12:a:- was first isolated in harbour
      porpoises (Phocoena phocoena) in Scotland in 1991. This paper reports the
      isolation of the same group B S enterica from harbour porpoise carcases found
      stranded along the Cornwall and Devon coastlines. Between 1991 and 2002, 80
      harbour porpoises were submitted for postmortem examination and subjected to
      bacteriological examination under the UK Cetacean Strandings Investigation
      Programme. A total of 28 Salmonella isolates were recovered and subjected to
      several tests, including biochemical, molecular and serological analysis.

PMID- 20675626
TI  - Use of a saline chaser to reduce the dose of contrast material for dynamic CT in
      cattle.
AB  - To investigate the effectiveness of a saline chaser in reducing the required dose
      of contrast material while carrying out dynamic CT scans in cattle, six
      clinically normal Holstein calves were subjected to CT scans of the head in a
      study using a crossover design. The calves were studied as three groups: group A
      received only contrast material (600 mgI/kg); group B received a 30 per cent
      lower dose of the same contrast material followed by 50 ml of saline solution;
      and group C received a 40 per cent lower dose of the same contrast material
      followed by 50 ml of saline solution. In all the animals, a power injector was
      used for administering the contrast material, with an injection rate of 4 ml/s
      and a pressure of 4.7 to 5.7 kg/cm(2). Attenuation values were obtained from the
      right and left maxillary arteries and dorsal sagittal sinus. There were no
      significant differences in the maximum enhancement value (MEV) of the maxillary
      arteries and dorsal sagittal sinus between groups A and B. The MEVs of the
      maxillary arteries and dorsal sagittal sinus in groups A and B were significantly
      greater than the MEV in group C (P<0.05). The use of a saline chaser allowed a 30
      per cent reduction in the dose of contrast material without decreasing vascular
      enhancement.

PMID- 20675628
TI  - Chronic rhinitis due to Streptococcus equi subspecies zooepidemicus in a dog.

PMID- 20675629
TI  - Secobarbital poisoning in an Amur tiger (Panthera tigris altaica).

PMID- 20675633
TI  - MRSA in pigs in Serbia.

PMID- 20675635
TI  - Mass mortalities in gulls associated with eating livestock fodder.

PMID- 20675636
TI  - Adenovirus in a red squirrel (Sciurus vulgaris) from Scotland.

PMID- 20675637
TI  - Preoperative embolization in the treatment of spinal metastasis.
AB  - Because of advances in the treatment of cancer, the average rate of patient
      survival is increasing. As patients with cancer live longer, the incidence of
      spinal metastasis also likely will increase. To help control pain and maintain
      function, some of these metastases will require surgical intervention. Because
      >60% of spinal metastases are hypervascular, preoperative embolization may be
      considered in order to decrease hemorrhage risk and improve outcomes.
      Embolization for spinal metastasis can be performed through the angiogram
      catheter. When such embolization is performed carefully, the complication rate is
      low.

PMID- 20675638
TI  - Randomized clinical trials in orthopaedic surgery: strategies to improve quantity
      and quality.
AB  - Randomized clinical trials (RCTs) generally provide the highest quality and least
      biased evidence for treatment effectiveness. Relatively few high-quality RCTs
      have been published in the orthopaedic literature. Barriers to increasing the
      quantity of trials include the orthopaedic culture, patient preferences, and the
      availability of treatment outside trials. Challenges to conducting better quality
      trials include sample size, random allocation, and blinding. Undertaking more
      high-quality trials can improve the evidence available for determining treatment
      effectiveness, resulting in better patient care.

PMID- 20675639
TI  - Therapy after injury to the hand.
AB  - Surgical and nonsurgical management of upper extremity disorders benefits from
      the collaboration of a therapist, the treating physician, and the patient. Hand
      therapy plays a role in many aspects of treatment, and patients with upper
      extremity injuries may spend considerably more time with a therapist than with a
      surgeon. Hand therapists coordinate edema control; pain management; minimization
      of joint contractures; maximization of tendon gliding, strengthening, and work
      hardening; counseling; and ongoing diagnostic evaluation. Modalities used to
      manage hand injuries include ultrasound, splinting, Fluidotherapy (Chattanooga
      Group, Chattanooga, TN), cryotherapy, various electrical modalities,
      phonophoresis, and iontophoresis.

PMID- 20675640
TI  - Metatarsalgia.
AB  - Metatarsalgia (ie, metatarsal pain) is one of the most common reports in patients
      with foot problems. This pain is confined to the area across the plantar
      forefoot, including the second through fourth metatarsal heads. However, it is
      frequently accompanied by deformity of the first and fifth rays as well as of the
      toes. There is great variability in possible causative factors, but all of them
      seem to be related to gait mechanics, foot anatomy, and foot and ankle deformity.
      An individualized treatment protocol is required. Nonsurgical management is
      usually sufficient to achieve satisfactory results. Surgical correction must be
      precise, and all pain-producing deformities must be corrected. Most patients
      present with abnormalities of the distal metatarsals. Metatarsal osteotomy, long
      a staple of treatment, always fails in the long term. Improved equipment and
      internal fixation methods may lead to better long-term outcomes.

PMID- 20675641
TI  - Bracing following correction of idiopathic clubfoot using the Ponseti method.
AB  - The Ponseti method for the management of idiopathic clubfoot has recently
      experienced a rise in popularity, with several centers reporting excellent
      outcomes. The challenge in achieving a successful outcome with this method lies
      not in correcting deformity but in preventing relapse. The most common cause of
      relapse is failure to adhere to the prescribed postcorrective bracing regimen.
      Socioeconomic status, cultural factors, and physician-parent communication may
      influence parental compliance with bracing. New, more user-friendly braces have
      been introduced in the hope of improving the rate of compliance. Strategies that
      may be helpful in promoting adherence include educating the family at the outset
      about the importance of bracing, encouraging calls and visits to discuss
      problems, providing clear written instructions, avoiding or promptly addressing
      skin problems, and refraining from criticism of the family when noncompliance is
      evident. A strong physician-family partnership and consideration of underlying
      cognitive, socioeconomic, and cultural issues may lead to improved adherence to
      postcorrective bracing protocols and better patient outcomes.

PMID- 20675642
TI  - Spinal epidural hematoma.
AB  - Spinal epidural hematoma is a rare condition that usually presents with acute,
      severe pain at the location of the hemorrhage, with radiation to the extremities.
      It can rapidly develop to include progressive and severe neurologic deficit. The
      pathophysiology often remains unclear. However, epidural hematoma in the lumbar
      spine is best described as the result of internal rupture of the Batson vertebral
      venous plexus. Clinical evaluation of pain control and neurologic deficit is the
      most important tool in early diagnosis. Currently, MRI is the diagnostic method
      of choice. Regardless of the setting, symptomatic spinal epidural hematoma is
      typically managed with urgent surgical decompression of the spinal canal.

PMID- 20675643
TI  - Diagnosis and treatment of acute Achilles tendon rupture.
AB  - This clinical practice guideline is based on a series of systematic reviews of
      published studies in the available literature on the diagnosis and treatment of
      acute Achilles tendon rupture. None of the 16 recommendations made by the work
      group was graded as strong; most are graded inconclusive; four are graded weak;
      two are graded as moderate strength; and two are consensus statements. The two
      moderate-strength recommendations include the suggestions for early postoperative
      protective weight bearing and for the use of protective devices that allow for
      postoperative mobilization.

PMID- 20675644
TI  - AAOS Clinical Practice Guideline: acute Achilles tendon rupture.

PMID- 20675645
TI  - Abolished synthesis of cholic acid reduces atherosclerotic development in
      apolipoprotein E knockout mice.
AB  - To investigate the effects of abolished cholic acid (CA) synthesis in the ApoE
      knockout model [apolipoprotein E (apoE) KO],a double-knockout (DKO) mouse model
      was created by crossbreeding Cyp8b1 knockout mice (Cyp8b1 KO), unable to
      synthesize the primary bile acid CA, with apoE KO mice. After 5 months of
      cholesterol feeding, the development of atherosclerotic plaques in the proximal
      aorta was 50% less in the DKO mice compared with the apoE KO mice. This effect
      was associated with reduced intestinal cholesterol absorption, decreased levels
      of apoB-containing lipoproteins in the plasma, enhanced bile acid synthesis,
      reduced hepatic cholesteryl esters, and decreased hepatic activity of ACAT2. The
      upregulation of Cyp7a1 in DKO mice seemed primarily caused by reduced expression
      of the intestinal peptide FGF15. Treatment of DKO mice with the farnesoid X
      receptor (FXR) agonist GW4064 did not alter the intestinal cholesterol
      absorption, suggesting that the action of CA in this process is confined mainly
      to formation of intraluminal micelles and less to its ability to activate the
      nuclear receptor FXR. Inhibition of CA synthesis may offer a therapeutic strategy
      for the treatment of hyperlipidemic conditions that lead to atherosclerosis.

PMID- 20675646
TI  - Computed tomography assessment of hip joints in asymptomatic individuals in
      relation to femoroacetabular impingement.

PMID- 20675647
TI  - Ben would approve.

PMID- 20675648
TI  - Dancing on the ceiling.

PMID- 20675649
TI  - Kinematic impact of anteromedial and posterolateral bundle graft fixation angles
      on double-bundle anterior cruciate ligament reconstructions.
AB  - BACKGROUND: Currently in double-bundle anterior cruciate ligament (ACL)
      reconstructions, the range of knee flexion angles that surgeons use for
      anteromedial (AM) and posterolateral (PL) bundle graft fixation spans from 0
      degrees to 90 degrees for both bundle grafts. Despite the recent popularity of
      this procedure, no consensus exists on an optimal set of AM and PL graft fixation
      angles. HYPOTHESIS: Graft fixation angles that simulate the native tensioning
      relationship of the AM and PL bundles will produce kinematic results similar to
      the intact knee, while graft fixation angles that do not simulate this
      relationship will under- or overconstrain the knee. STUDY DESIGN: Controlled
      laboratory study. METHODS: Twelve cadaveric knees were biomechanically tested in
      the intact state, ACL-sectioned state, and a randomized order of 7 double-bundle
      ACL reconstructed states at multiple graft fixation angle combinations. For each
      test state, data were collected for 88 N anterior tibial loads, 10 N.m valgus
      torques, 5 N.m internal rotation torques, and 2 simulated pivot shift loads
      consisting of a 5 N.m internal rotation torque coupled with either a 10 N.m
      valgus torque or an 88 N anterior tibial load at 0 degrees, 20 degrees, 30
      degrees, 60 degrees, and 90 degrees of knee flexion. RESULTS: The AM and PL graft
      fixation angle combinations of 0 degrees /0 degrees (AM graft fixation angle/PL
      graft fixation angle), 60 degrees /0 degrees, 45 degrees /15 degrees, and 75
      degrees /15 degrees restored normal laxity to the reconstructed knee in all of
      the biomechanical tests. The 30 degrees /30 degrees, 60 degrees /60 degrees, and
      90 degrees /90 degrees graft fixation angle combinations significantly restricted
      knee laxity compared with the intact state in various biomechanical tests.
      CONCLUSION: We found that as long as the PL bundle graft was fixed between 0
      degrees and 15 degrees , the AM graft could be fixed up to 75 degrees without
      restricting knee laxity. However, fixation of the PL graft at 30 degrees of knee
      flexion and above significantly overconstrained the knee. CLINICAL RELEVANCE:
      This study provides a range of angles that can be used in double-bundle ACL
      reconstructions to restore normal knee stability without causing overconstraint.

PMID- 20675650
TI  - Structural properties of the primary medial knee ligaments.
AB  - BACKGROUND: The structural properties of the individual components of the
      superficial medial collateral ligament (MCL), deep MCL, and posterior oblique
      ligament (POL) have not been studied in isolation. To define the necessary
      strength requirements for an anatomical medial knee reconstruction, knowledge of
      these structural properties is necessary. HYPOTHESIS: The components of the
      superficial MCL, POL, and deep MCL have significantly different structural
      properties. STUDY DESIGN: Controlled laboratory study. METHODS: This study used
      20 fresh-frozen nonpaired cadaveric knee specimens with a mean age of 54 years
      (range, 27 to 68 years). These knees provided 8 samples for each tested medial
      knee structure, which was individually isolated and loaded to failure at 20 mm
      per minute. Specifically tested were the superficial MCL with intact femoral and
      detached proximal tibial attachments, the superficial MCL with intact femoral and
      detached distal tibial attachments, the central arm of the POL, and the isolated
      deep MCL. Load was recorded as a function of displacement. Stiffness of the
      ligament at failure was calculated from these measurements. RESULTS: The mean
      load at failure for the superficial MCL with the intact femoral and distal tibial
      attachments was 557 N. Mean load at failure was 88 N for the intact femoral and
      proximal tibial divisions of the superficial MCL, 256 N for the POL, and 101 N
      for the deep MCL. Stiffness of the ligaments just before failure was 63, 17, 38,
      and 27 N/mm, in the same order as above. CONCLUSION: The proximal and distal
      tibial divisions of the superficial MCL, POL, and deep MCL produced loads of
      clinical importance. CLINICAL RELEVANCE: Knowledge of the structural properties
      of these attachment sites will assist in reconstruction graft choices, fixation
      method choices, and overall operative treatment of medial knee injury.

PMID- 20675651
TI  - Anatomic posterolateral knee reconstructions require a popliteofibular ligament
      reconstruction through a tibial tunnel.
AB  - BACKGROUND: No biomechanical study has been performed analyzing the merits of
      reconstructing the popliteofibular ligament (PFL) through a tibial tunnel with an
      anatomic reconstruction of the posterolateral knee. HYPOTHESIS: There is no
      difference in an anatomic posterolateral knee reconstruction with or without a
      PFL reconstruction placed through a tibial tunnel in restoring knee motion to the
      intact, uninjured state, and the knee is not overconstrained with this
      reconstruction. STUDY DESIGN: Controlled laboratory study. METHODS: Eight paired
      knees were tested in the intact state and then sectioned to simulate a grade III
      posterolateral knee injury. The reconstruction for the first paired knee
      reconstructed the PFL (through a tibial tunnel), popliteus tendon, and fibular
      collateral ligament (group 1); the matched knee reconstruction involved only the
      popliteus tendon and fibular collateral ligament (group 2). RESULTS:
      Reconstructions for group 1 knees restored knee motion to the intact state for
      all tested conditions at all knee flexion angles with no overconstraint of the
      knee. Without reconstructing the PFL (group 2), small but significant increases
      in motion were found for varus translation at 0 degrees (3.0 degrees ), 20
      degrees (3.1 degrees ), and 60 degrees (3.8 degrees ) of knee flexion compared
      with the intact state. At 60 degrees and 90 degrees of flexion, the
      reconstruction for group 2 had small but significant increases in internal
      rotation compared with the intact state (1.3 degrees and 1.8 degrees ,
      respectively). CONCLUSION: Inclusion of the PFL through a tibial tunnel as part
      of an anatomic posterolateral knee reconstruction restores knee stability back to
      the intact state and does not overconstrain the knee. Furthermore, inclusion of
      the PFL through a tibial tunnel restored normal internal rotation. CLINICAL
      RELEVANCE: The PFL should be included in anatomic reconstructions of grade III
      posterolateral knee injuries with placement through a tibial tunnel to best
      restore the intact, preinjury knee motion state and, most notably, normal
      internal rotation without evidence of overconstraint of the knee.

PMID- 20675652
TI  - Injuries to the pectoralis major muscle: diagnosis and management.
AB  - Injuries to the pectoralis major muscle are relatively infrequent but result in
      pain, weakness, and deformity of the upper extremity. The usual injury mechanism
      is during eccentric shortening of the pectoralis major under heavy load, such as
      when performing a bench press exercise. The ability to detect and treat a
      pectoralis major rupture is important for both the clinician and the patient and
      is aided with knowledge of the anatomy, the clinical findings, and results of
      nonoperative and operative care. It is important to understand the physical
      demands and desires of the patient as well as to understand the outcomes of both
      nonoperative and operative care to make an informed decision regarding optimal
      treatment. This article highlights the importance of the clinical examination in
      identifying the injury, examines various surgical techniques to repair the
      rupture, and reports on potential complication and reinjury rates.

PMID- 20675655
TI  - Rad18-mediated translesion synthesis of bulky DNA adducts is coupled to
      activation of the Fanconi anemia DNA repair pathway.
AB  - Fanconi anemia (FA) is a cancer susceptibility syndrome characterized by
      sensitivity to DNA-damaging agents. The FA proteins (FANCs) are implicated in DNA
      repair, although the precise mechanisms by which FANCs process DNA lesions are
      not fully understood. An epistatic relationship between the FA pathway and
      translesion synthesis (TLS, a post-replication DNA repair mechanism) has been
      suggested, but the basis for cross-talk between the FA and TLS pathways is poorly
      understood. We show here that ectopic overexpression of the E3 ubiquitin ligase
      Rad18 (a central regulator of TLS) induces DNA damage-independent mono
      ubiquitination of proliferating cell nuclear antigen (PCNA) (a known Rad18
      substrate) and FANCD2. Conversely, DNA damage-induced mono-ubiquitination of both
      PCNA and FANCD2 is attenuated in Rad18-deficient cells, demonstrating that Rad18
      contributes to activation of the FA pathway. WT Rad18 but not an E3 ubiquitin
      ligase-deficient Rad18 C28F mutant fully complements both PCNA ubiquitination and
      FANCD2 activation in Rad18-depleted cells. Rad18-induced mono-ubiquitination of
      FANCD2 is not observed in FA core complex-deficient cells, demonstrating that
      Rad18 E3 ligase activity alone is insufficient for FANCD2 ubiquitylation.
      Instead, Rad18 promotes FA core complex-dependent FANCD2 ubiquitination in a
      manner that is secondary to PCNA mono-ubiquitination. Taken together, these
      results demonstrate a novel Rad18-dependent mechanism that couples activation of
      the FA pathway with TLS.

PMID- 20675656
TI  - Polyembryony in non-apomictic citrus genotypes.
AB  - BACKGROUND AND AIMS: Adventitious embryony from nucellar cells is the mechanism
      leading to apomixis in Citrus sp. However, singular cases of polyembryony have
      been reported in non-apomictic genotypes as a consequence of 2x * 4x
      hybridizations and in vitro culture of isolated nucelli. The origin of the plants
      arising from the aforementioned processes remains unclear. METHODS: The genetic
      structure (ploidy and allelic constitution with microsatellite markers) of plants
      obtained from polyembryonic seeds arising from 2x * 4x sexual hybridizations and
      those regenerated from nucellus culture in vitro was systematically analysed in
      different non-apomictic citrus genotypes. Histological studies were also
      conducted to try to identify the initiation process underlying polyembryony. KEY
      RESULTS: All plants obtained from the same undeveloped seed in 2x * 4x
      hybridizations resulted from cleavage of the original zygotic embryo. Also, the
      plants obtained from in vitro nucellus culture were recovered by somatic
      embryogenesis from cells that shared the same genotype as the zygotic embryos of
      the same seed. CONCLUSIONS: It appears that in non-apomictic citrus genotypes,
      proembryos or embryogenic cells are formed by cleavage of the zygotic embryos and
      that the development of these adventitious embryos, normally hampered, can take
      place in vivo or in vitro as a result of two different mechanisms that prevent
      the dominance of the initial zygotic embryo.

PMID- 20675657
TI  - Palliative care for people with dementia.
AB  - The number of people with dementia will rise dramatically over the next 20 years.
      Currently, one in three people over the age of 65 will die with dementia. A
      PubMed search using MeSH headings for 'dementia' AND 'palliative care' and for
      specific areas, i.e. enteral feeding. National reports, UK guidelines and
      policies were also consulted. Advanced dementia is now being perceived as a
      'terminal illness' with a similar symptom burden and prognosis to advanced
      cancer. People with dementia have poor access to good quality end-of-life care.
      Interventions such as antibiotics, fever management policies and enteral tube
      feeding remain in use despite little evidence that they improve quality of life
      or other outcomes. Research is required on the effectiveness of 'holistic'
      palliative care, outcome measures and the impact on carers and families.

PMID- 20675658
TI  - C-reactive protein is a bystander of cardiovascular disease.
AB  - A large number of studies have evaluated the association of hs-C-reactive protein
      with atherosclerosis and coronary heart disease (CHD) in mechanistic, genetic,
      population-based studies, as well as clinical trials. This paper reviews the
      collective evidence to determine if hs-C-reactive protein is part of the causal
      pathway of atherosclerosis and CHD or whether it is a bystander.

PMID- 20675659
TI  - Covered stents in giant coronary artery aneurysm.

PMID- 20675660
TI  - Impact of early vs. late microvascular obstruction assessed by magnetic resonance
      imaging on long-term outcome after ST-elevation myocardial infarction: a
      comparison with traditional prognostic markers.
AB  - AIMS: Early and late microvascular obstruction (MO) assessed by magnetic
      resonance imaging (MRI) are prognostic markers for combined clinical endpoints
      after ST-elevation myocardial infarction (STEMI). However, there are only limited
      data for hard endpoints and no consensus exists which of the two best predicts
      clinical outcome. Furthermore, it is unclear whether the assessment of MO by MRI
      adds incremental prognostic information independent of traditional outcome
      markers. METHODS AND RESULTS: STEMI patients reperfused by primary angioplasty (n
      = 438) < 12 h after symptom onset underwent MRI at a median of 3 days after the
      index event. Microvascular obstruction was measured 1 and 15 min after gadolinium
      injection (early and late MO). Clinical follow-up was conducted after a median of
      19 months. The primary endpoint was defined as a composite of death, non-fatal
      myocardial re-infarction, and congestive heart failure. In contrast to the
      presence and extent of early MO, the presence and extent of late MO were
      independently associated with the composite primary endpoint in the multivariable
      Cox regression analysis adjusting for post-percutaneous coronary intervention
      TIMI-flow, ST-resolution, TIMI-risk score, ejection fraction, and infarct size.
      The presence of late MO was identified as the strongest independent predictor for
      the occurrence of the composite endpoint (hazard ratio 4.23, 95%CI 1.73-10.34, P
      = 0.002). Furthermore, the presence and extent of late MO provided an incremental
      prognostic value above the traditional prognostic markers. CONCLUSION: In
      contrast to early MO, the presence and extent of late MO are strong independent
      prognosticators after STEMI. www.ClinicalTrials.gov: NCT00299377.

PMID- 20675661
TI  - Cardiac and peripheral adjustments induced by early exercise training
      intervention were associated with autonomic improvement in infarcted rats: role
      in functional capacity and mortality.
AB  - AIMS: To test the effects of early exercise training (ET) on left ventricular
      (LV) and autonomic functions, haemodynamics, tissues blood flows (BFs), maximal
      oxygen consumption (VO(2) max), and mortality after myocardial infarction (MI) in
      rats. METHODS AND RESULTS: Male Wistar rats were divided into: control (C),
      sedentary-infarcted (SI), and trained-infarcted (TI). One week after MI, TI group
      underwent an ET protocol (90 days, 50-70% VO(2) max). Left ventricular function
      was evaluated non-invasively and invasively. Baroreflex sensitivity, heart rate
      variability, and pulse interval were measured. Cardiac output (CO) and regional
      BFs were determined using coloured microspheres. Infarcted area was reduced in TI
      (19 +/- 6%) compared with SI (34 +/- 5%) after ET. Exercise training improved the
      LV and autonomic functions, the CO and regional BF changes induced by MI, as well
      as increased SERCA2 expression and mRNA vascular endothelial growth factor
      levels. These changes brought about by ET resulted in mortality rate reduction in
      the TI (13%) group compared with the SI (54%) group. CONCLUSION: Early aerobic ET
      reduced cardiac and peripheral dysfunctions and preserved cardiovascular
      autonomic control after MI in trained rats. Consequently, these ET-induced
      changes resulted in improved functional capacity and survival after MI.

PMID- 20675662
TI  - Intolerance to beta-blockade in a mouse model of delta-sarcoglycan-deficient
      muscular dystrophy cardiomyopathy.
AB  - AIMS: Patients with mutations predisposing to cardiomyopathy often have routine
      assessments of left ventricular function. It is unclear whether asymptomatic mild
      cardiomyopathy should be treated with standard heart failure therapies. METHODS
      AND RESULTS: We tested the effect of metoprolol on cardiac haemodynamics and
      pathology in two animal models for muscular dystrophy and cardiomyopathy.
      Treatment started at an early stage in the development of the cardiomyopathy.
      Metoprolol was given orally (2.5 mg/kg/day) over 8 weeks to mdx mice (model for
      Duchenne muscular dystrophy) and delta-sarcoglycan-deficient (Sgcd(null)) mice
      (model for Limb girdle muscular dystrophy type 2F). In vivo pressure-volume
      loops, fibrosis, in vivo myocyte sarcolemmal injury, and beta-adrenergic receptor
      mRNA were assessed. In beta-blocked mdx mice, there was a beneficial reduction in
      afterload and restored contractility resulting in an increased stroke volume. In
      contrast, in Sgcd(null) mice, there was marked deterioration in haemodynamics
      (prolonged relaxation, Tau, and reduced stroke volume). Furthermore, challenging
      the beta-blocked Sgcd(null) mice with the beta-adrenergic agonist dobutamine led
      to markedly increased mortality. Patterns of sarcolemmal injury or beta
      adrenergic receptor mRNA could not account for this, though the acute rise in
      markers of active relaxation suggested abnormally high levels of intracellular
      calcium. CONCLUSION: beta-Blockers may not necessarily be beneficial in all
      cardiomyopathies, even when given at an early stage of development. Clinical
      trials of beta-blockers in muscular dystrophy-associated cardiomyopathy may need
      to stratify patients by genotype.

PMID- 20675663
TI  - Elevated pulmonary artery systolic pressure in patients with coronary artery
      disease and left ventricular dyssynchrony.
AB  - AIMS: We sought to determine whether inter- or intra-ventricular systolic
      dyssynchrony contributes to the occurrence of elevated pulmonary artery systolic
      pressure (PASP) in patients with coronary artery disease (CAD). METHODS AND
      RESULTS: One hundred and fifty-three consecutive CAD patients with preserved left
      ventricular ejection fraction (LVEF >40%) were enrolled. Detailed
      echocardiography was performed to measure PASP, inter-ventricular dyssynchrony
      (Ts-RL: time difference between lateral and right free wall), and intra
      ventricular dyssynchrony (Ts-SD, standard deviation of time to peak systolic
      velocity of 12 LV segments; Ts-12, maximal difference in Ts between any 2 of 12
      LV segments; Ts-6-basal, maximal difference in Ts between any 2 of 6 basal LV
      segments). Elevated PASP (>35 mmHg) was confirmed in 46 patients who had
      significantly prolonged intra-ventricular dyssynchrony (Ts-SD: 49.9 +/- 19.6
      vs.37.9 +/- 19.8 ms; Ts-12: 147.9 +/- 56.4 vs.110.9 +/- 53.9 ms; Ts-6-basal:
      114.2 +/- 51.9 vs. 85.7 +/- 48.5 ms, all P < 0.01) and inter-ventricular
      dyssynchrony (Ts-RL: 78.7 +/- 46.4 vs. 62.7 +/- 34.3 ms, P = 0.019) compared with
      those without elevated PASP. Indexes of intra- and inter-ventricular dyssynchrony
      and LV filling pressure (E/e') were significantly correlated with PASP.
      Multivariate analysis showed that left atrial dimension [odds ratio (OR) 4.23,
      95% confidence interval (CI) 1.64-10.90], E/e' septal (OR 1.15, 95% CI 1.04
      1.27), pulmonary vascular resistance (OR 5.38, 95% CI 1.55-18.74), and Ts-RL (OR
      1.02, 95% CI 1.01-1.03) were independent predictors for the occurrence of
      elevated PASP (all P < 0.05). CONCLUSION: Elevated PASP is common in CAD patients
      with preserved LVEF and is associated with LV diastolic dysfunction and LV
      mechanical dyssynchrony.

PMID- 20675664
TI  - Current state of knowledge on aetiology, diagnosis, management, and therapy of
      peripartum cardiomyopathy: a position statement from the Heart Failure
      Association of the European Society of Cardiology Working Group on peripartum
      cardiomyopathy.
AB  - Peripartum cardiomyopathy (PPCM) is a cause of pregnancy-associated heart
      failure. It typically develops during the last month of, and up to 6 months
      after, pregnancy in women without known cardiovascular disease. The present
      position statement offers a state-of-the-art summary of what is known about risk
      factors for potential pathophysiological mechanisms, clinical presentation of,
      and diagnosis and management of PPCM. A high index of suspicion is required for
      the diagnosis, as shortness of breath and ankle swelling are common in the
      peripartum period. Peripartum cardiomyopathy is a distinct form of
      cardiomyopathy, associated with a high morbidity and mortality, but also with the
      possibility of full recovery. Oxidative stress and the generation of a
      cardiotoxic subfragment of prolactin may play key roles in the pathophysiology of
      PPCM. In this regard, pharmacological blockade of prolactin offers the
      possibility of a disease-specific therapy.

PMID- 20675665
TI  - A unified view of ventricular remodelling.

PMID- 20675666
TI  - Exercise training in Chagas' cardiomyopathy: trials are welcome for this
      neglected heart disease.

PMID- 20675667
TI  - Cardiac remodelling and myocardial recovery: lost in translation?
AB  - The insight that decreases in left ventricular (LV) volume and mass occur
      secondary to the recovery of the myocardium at the cellular and molecular level
      has engendered a wider appreciation of the importance of LV remodelling as a
      mechanism for worsening heart failure. Despite these recent insights into the
      recognition of the importance of LV reverse remodelling in heart failure, many
      clinicians do not consider simple measurements of LV structure (i.e. LV volume)
      in their routine clinical decision-making process, preferring instead to rely on
      measurements of LV function [e.g. ejection fraction (EF)] when making decisions
      about medical and surgical treatment options. Although there are probably
      multiple reasons of why the use of LV volumes has not gained wider acceptance in
      day-to-day clinical management of heart failure patients, the most likely reason
      is that clinicians remain extremely comfortable using the LVEF to assess their
      heart failure patients. Importantly, LV volumes predict outcome more reliably
      than does the EF. Moreover, knowledge regarding LV volumes is extremely useful in
      optimizing patient selection for surgical and device therapies. Based on the
      foregoing arguments, we suggest that it is time to begin developing
      individualized clinical strategies based upon a consideration of the important
      role that LV remodelling plays in the pathogenesis of heart failure, and that we
      begin to incorporate measurements of LV volume and mass into the clinical
      decision-making process.

PMID- 20675669
TI  - A randomized trial of the effects of exercise training in Chagas cardiomyopathy.
AB  - AIMS: The effects of exercise training in chronic heart failure are well
      established, however, they have not been evaluated in Chagas cardiomyopathy
      (ChC). We sought to determine the effects of exercise training on functional
      capacity, health-related quality of life (HQoL), and brain natriuretic peptide
      (BNP) levels in patients with ChC. METHODS AND RESULTS: This randomized,
      controlled, single-blind trial included 40 patients with ChC (age 49.5 +/- 7.8
      years, 57.5% male) who did not practice regular exercise. All patients were
      assessed, at baseline and at the end of the study, by exercise test (VO(2) and
      exercise time), six-minute walk test (6MWT), Goldman Specific Activity Scale
      (SAS), HQoL, and BNP levels. Patients were randomized to inactive control group
      (ICG = 19) or exercise training group (ETG = 21). Exercise training group
      patients underwent 12 weeks of exercise training: walking for up to 30 min
      (intensity 50-70% HR reserve + HR at rest) and warm-up and cooling-down
      exercising, three times a week. The data were analysed for delta values (Delta=
      end - baseline). After intervention, compared with the ICG, the ETG had
      significant increases in functional parameters including, DeltaVO(2) (6.5 vs. 2.8
      mL/kg/min, P = 0.001), Delta exercise time (2.9 vs.1.1 min, P < 0.001), Delta6MWT
      distance (83.5 vs. 2.0 m, P = 0.001) improved DeltaSAS (8 vs. 1 patient, P =
      0.008), and HQoL: Delta domains vitality (7.5 vs. 0 points, P = 0.013), Delta
      emotional aspects (16.7 vs. 0 points, P = 0.012), and Delta mental health (16.1
      vs. 0 points, P = 0.031). There was no difference in BNP levels. CONCLUSION: In
      patients with ChC, exercise training was associated with a major improvement in
      functional capacity and HQoL without any adverse effects.

PMID- 20675668
TI  - Relations of serum phosphorus levels to echocardiographic left ventricular mass
      and incidence of heart failure in the community.
AB  - AIMS: To evaluate the association of serum phosphorus with cardiac
      structure/function and incident heart failure. METHODS AND RESULTS: We related
      serum phosphorus to echocardiographic left ventricular (LV) measurements cross
      sectionally, and to incident heart failure prospectively in 3300 participants
      (mean age 44 years, 51% women) free of heart failure, myocardial infarction, and
      chronic kidney disease (estimated glomerular filtration rate [eGFR]<60
      mL/min/1.73 m(2)). Cross-sectionally, serum phosphorus was related positively to
      LV mass, internal dimensions, and systolic dysfunction. On follow-up (mean 17.4
      years), 157 individuals developed heart failure. In models adjusting for
      established risk factors as time-varying covariates, each mg/dL increment in
      serum phosphorus was associated with a 1.74-fold risk of heart failure [95%
      confidence intervals (CI) 1.17-2.59]. Individuals in the highest serum phosphorus
      quartile experienced a two-fold (95% CI 1.28-3.40) risk of heart failure compared
      with participants in the lowest quartile. These relations were maintained upon
      additional adjustment for LV mass/dimensions and systolic dysfunction. In
      analyses restricted to individuals with eGFR >90 mL/min/1.73 m(2), no proteinuria
      and serum phosphorus <4.5 mg/dL, the association of serum phosphorus with heart
      failure remained robust. CONCLUSION: In our community-based sample, higher serum
      phosphorus was associated with greater LV mass cross-sectionally, and with an
      increased risk of heart failure prospectively.

PMID- 20675671
TI  - Correspondence concerning the article: is levosimendan better than dobutamine in
      acute heart failure in patients on beta blockade treatment? What is the evidence?

PMID- 20675672
TI  - How to treat acute decompensated heart failure in the 'beta-blocker era'?

PMID- 20675673
TI  - Skeletal myoblast implants induce minor propagation delays, but do not promote
      arrhythmias in the normal swine heart.
AB  - AIMS: Whether skeletal myoblast (SM) implants are proarrhythmic is still
      controversial due to conflicting pre-clinical and clinical data. We hypothesized
      that if SM implants are arrhythmogenic, they will facilitate the induction of
      ventricular tachyarrhythmias by promoting heterogeneous propagation of activation
      wavefronts. METHODS: Skeletal myoblast cells were harvested from 10 pigs. A month
      later, 125 +/- 37 * 10(6) cells were subepicardially injected in an area of ~2
      cm(2) at the anterolateral aspect of the left ventricle. Four weeks later, a
      ventricular stimulation protocol was conducted. Once explanted, epicardial
      wavefronts over SM and adjacent control areas were optically mapped. Eight saline
      injected animals were used as controls. To compare with clear arrhythmogenic
      substrates, propagation patterns were also evaluated in infarcted hearts and on a
      SM-implanted heart following amiodarone infusion. RESULTS: In SM hearts, fibrosis
      and differentiated SM cells were consistently found and no tachyarrhythmias were
      induced. Wavefronts propagated homogeneously over SM and adjacent areas, with no
      late activation zones, as opposed to the infarcted hearts. The time required for
      the wavefronts to depolarize both areas were similar, becoming only slightly
      longer at SM areas after an extra-stimulus (P = 0.025). Conduction velocities and
      APD(90) were also similar. Saline hearts showed similar results. The extent of
      the conduction delay was not related to the number of injected SM cells.
      CONCLUSION: In normal swine hearts, myoblast implants promote localized fibrosis
      and slightly retard epicardial wavefront propagation only after extra-stimuli.
      However, SM implants are not associated with local re-entry and do not facilitate
      ventricular tachyarrhythmias in the whole normal heart.

PMID- 20675674
TI  - EHRA Expert Consensus Statement on the management of cardiovascular implantable
      electronic devices in patients nearing end of life or requesting withdrawal of
      therapy.
AB  - The purpose of this Consensus Statement is to focus on implantable cardioverter
      defibrillator (ICD) deactivation in patients with irreversible or terminal
      illness. This statement summarizes the opinions of the Task Force members,
      convened by the European Heart Rhythm Association (EHRA) and the Heart Rhythm
      Society (HRS), based on ethical and legal principles, as well as their own
      clinical, scientific, and technical experience. It is directed to all healthcare
      professionals who treat patients with implanted ICDs, nearing end of life, in
      order to improve the patient dying process. This statement is not intended to
      recommend or promote device deactivation. Rather, the ultimate judgement
      regarding this procedure must be made by the patient (or in special conditions by
      his/her legal representative) after careful communication about the
      deactivation's consequences, respecting his/her autonomy and clarifying that
      he/she has a legal and ethical right to refuse it. Obviously, the physician asked
      to deactivate the ICD and the industry representative asked to assist can
      conscientiously object to and refuse to perform device deactivation.

PMID- 20675675
TI  - Surviving the night in the ICU: who needs senior intensivists?

PMID- 20675676
TI  - 24-hour staffing of intensive care units by trained specialists: one leap at a
      time.

PMID- 20675677
TI  - Air pollution, population vulnerability, and standards for ambient air quality.

PMID- 20675679
TI  - High exposure to passive tobacco smoking and the development of asthma in an
      adult patient who had never smoked.

PMID- 20675680
TI  - Compromised T-cell immunity and virus-like structure in a patient with pulmonary
      hypertension.

PMID- 20675681
TI  - Prediction of arterial oxygen tension: validation of a novel formula.

PMID- 20675678
TI  - Cystic fibrosis pulmonary guidelines: pulmonary complications: hemoptysis and
      pneumothorax.
AB  - RATIONALE: Cystic fibrosis (CF) is a recessive genetic disease characterized by
      dehydration of the airway surface liquid and impaired mucociliary clearance. As a
      result, individuals with the disease have difficulty clearing pathogens from the
      lung and experience chronic pulmonary infections and inflammation. There may be
      intermittent pulmonary exacerbations or acute worsening of infection and
      obstruction, which require more intensive therapies. Hemoptysis and pneumothorax
      are complications commonly reported in patients with cystic fibrosis. OBJECTIVES:
      This document presents the CF Foundation's Pulmonary Therapies Committee
      recommendations for the treatment of hemoptysis and pneumothorax. METHODS: The
      committee recognized that insufficient data exist to develop evidence-based
      recommendations and so used the Delphi technique to formalize an expert panel's
      consensus process and develop explicit care recommendations. MEASUREMENTS AND
      MAIN RESULTS: The expert panel completed the survey twice, allowing refinement of
      recommendations. Numeric responses to the questions were summarized and applied
      to a priori definitions to determine levels of consensus. Recommendations were
      then developed to practical treatment questions based upon the median scores and
      the degree of consensus. CONCLUSIONS: These recommendations for the management of
      the patient with CF with hemoptysis and pneumothorax are designed for general use
      in most individuals but should be adapted to meet specific needs as determined by
      the individuals, their families, and their health care providers. It is hoped
      that the guidelines provided in this manuscript will facilitate the appropriate
      application of these treatments to improve and extend the lives of all
      individuals with cystic fibrosis.

PMID- 20675682
TI  - Severe acute respiratory syndrome and venous thromboembolism in multiple organs.

PMID- 20675683
TI  - Diagnostic accuracy: theoretical models for preimplantation genetic testing of a
      single nucleus using the fluorescence in situ hybridization technique.
AB  - BACKGROUND: The aim of this study was to develop and use theoretical models to
      investigate the accuracy of the fluorescence in situ hybridization (FISH)
      technique in testing a single nucleus from a preimplantation embryo without the
      complicating effect of mosaicism. METHODS: Mathematical models were constructed
      for three different applications of FISH in preimplantation genetic testing (sex
      determination for sex-linked diseases, two-way reciprocal translocations and
      sporadic chromosome aneuploidy). The input values were the degree of aneuploidy
      (initially set at 3% per chromosome for sporadic aneuploidy) and the accuracy per
      probe (initially set at 95%), defined as the proportion of normal diploid nuclei
      with a normal signal pattern. The primary statistic was the predictive value of
      the test result. RESULTS: Testing two chromosome pairs to determine sex
      chromosome status or detect unbalanced translocation products had high predictive
      value: at least 99.5% for a normal test result (95% CI: 99-100%), and 90% for an
      abnormal test result (95% CI: 88-92%). However, the predictive value of an
      abnormal test result testing five chromosomes for sporadic chromosome aneuploidy
      was 41% (95% CI: 36-46%); 90% would be achieved with an aneuploidy rate per
      chromosome of 20.3% (equivalent to 99.5% prevalence for 23 chromosomes) rather
      than 3%, or with an accuracy per probe of 99.6% rather than 95%, or when testing
      23 chromosome pairs, rather than 5 pairs, with either 8.3% aneuploidy (86.4%
      prevalence) or 99.5% accuracy. CONCLUSIONS: Testing a single cell using the FISH
      technique has the potential to achieve acceptable analytical performance for sex
      determination and two-way reciprocal translocations, but is unlikely to achieve
      adequate performance testing for sporadic chromosome aneuploidy. New techniques
      for detecting the copy number of every chromosome are emerging, but it remains to
      be seen if the high accuracy required will be achieved.

PMID- 20675684
TI  - Characterization of human single-chain antibodies against highly pathogenic avian
      influenza H5N1 viruses: mimotope and neutralizing activity.
AB  - The development of new therapeutic targets and strategies to control highly
      pathogenic avian influenza (HPAI) H5N1 virus infection in humans is urgently
      needed. Neutralizing recombinant human antibodies would provide important agents
      for immunotherapy on human H5N1 virus infection and definition of the critical
      mimotope for vaccine development. In this study, we have characterized an anti-H5
      specific scFv clone, 3D1 from the human-scFv-displaying phage library. 3D1
      blocked the binding of H5-Fc to MDCK cells in flow cytometry and neutralized H5N1
      subtype influenza A viruses in a microneutralization assay. Employing a peptide
      displaying phage library, Ph.D-12, the mimotope was determined to be at #128-131
      and #204-211 of H5, which are silic acid-binding regions. In consistency with
      this result, 3D1 binds the recombinant sugar-binding domain (#50G-#272E) produced
      by a baculovirus vector. The 3D1 antibody employs the germline gene VH1-23. As
      this antibody is the first human anti-H5 scFv clearly defined on the sugar
      binding epitope, it allows us to investigate the influence of amino acid
      substitutions in this region on the determination of the binding specificity to
      either sialic acid alpha2,6-galactose (SA alpha2,6Gal) or sialic acid alpha2,3
      galactose (SA alpha2,3Gal) providing new insight for the development of effective
      H5N1 pandemic vaccines.

PMID- 20675685
TI  - Beyond genomic imprinting.

PMID- 20675686
TI  - Engineering mouse models to investigate the function of imprinting.
AB  - Some insight into the developmental basis for imprinting specific genes during
      the evolution of mammals can be gained from conventional gene 'knockout' studies.
      However, the consequences of full loss of function are often wide-ranging and may
      obscure the critical, dosage-related phenotype. This review focuses on transgenic
      techniques employed to alter the dosage of imprinted genes, including the
      application of bacterial artificial chromosome transgenic mice, in imprinting
      research. Advantages of dosage-based techniques over conventional knockout
      studies will be discussed, with examples. Important applications of transgenic
      mice in imprinting research, including studying gene expression patterns, the
      identification of imprinting centres and isolating the consequences of altered
      gene dosage, are reviewed with a particular focus on the imprinted domain on
      mouse distal chromosome 7.

PMID- 20675687
TI  - How genome-wide approaches can be used to unravel the remaining secrets of the
      imprintome.
AB  - Genomic imprinting is the differential expression of genes according to their
      transmitting parent and is achieved by labelling of the two alleles with
      different epigenetic marks. The majority of described imprinted genes are present
      in clusters with coordinate regulation. Multiple mechanisms are known to regulate
      this differential expression, including repression of one allele by the action of
      cis-acting macro non-coding RNAs, insulator elements, allele specific histone
      modifications and DNA methylation. A hallmark of all imprinted regions described
      so far is the presence of one or more differentially methylated regions (DMRs). A
      DMR is a nucleotide sequence rich in CpG dinucleotides that is specifically
      methylated on one parental chromosome and unmethylated on the allele derived from
      the other parent. This parent-specific differential methylation may be imparted
      during spermatogenesis or oogenesis (as is the case for gametic DMRs) or may be
      acquired during embryogenesis (somatic DMRs). This review will describe the
      advantages and disadvantages of some of the techniques that can be used to
      compare epigenetic marks between parental chromosomes and to understand how these
      marks affect the 3D interactions and monoallelic expression at imprinted loci.
      Recent advances in sequencing technologies, in particular, provide exciting new
      opportunities to study imprinting. These analyses are likely to lead to the full
      characterization of the 'imprintome', which includes uncovering the totality of
      imprinted genes within a genome, their epigenetic landscape and unique features
      that render them resistant to epigenetic reprogramming in the early embryo.

PMID- 20675688
TI  - Efficacy of motivational interviewing for smoking cessation: a systematic review
      and meta-analysis.
AB  - OBJECTIVE: A systematic review and meta-analysis to investigate the efficacy of
      interventions incorporating motivational interviewing for smoking cessation and
      identify correlates of treatment effects. DATA SOURCES: Medline/PubMed, PsycInfo
      and other sources including grey literature. STUDY SELECTION: Title/abstract
      search terms were motivational interview* OR motivational enhancement AND smok*,
      cigarette*, tobacco, OR nicotine. Randomised trials reporting number of smokers
      abstinent at follow up were eligible. DATA EXTRACTION: Data were independently
      coded by the first and third authors. We coded for a variety of study,
      participant, and intervention related variables. DATA SYNTHESIS: A random effects
      logistic regression with both a random intercept and a random slope for the
      treatment effect. RESULTS: 31 smoking cessation research trials were selected for
      the study: eight comprised adolescent samples, eight comprised adults with
      chronic physical or mental illness, five comprised pregnant/postpartum women and
      10 comprised other adult samples. Analysis of the trials (9485 individual
      participants) showed an overall OR comparing likelihood of abstinence in the
      motivational interviewing (MI) versus control condition of OR 1.45 (95% CI 1.14
      to 1.83). Additional potential correlates of treatment effects such as study,
      sample, and intervention characteristics were examined. CONCLUSIONS: This is the
      most comprehensive review of MI for smoking cessation conducted to date. These
      findings suggest that current MI smoking cessation approaches can be effective
      for adolescents and adults. However, comparative efficacy trials could be useful.

PMID- 20675689
TI  - Area deprivation, individual socioeconomic position and smoking among women in
      South Korea.
AB  - BACKGROUND: The objective of this study was to examine how area deprivation and
      individual socioeconomic position affect smoking among women using national
      survey data. METHODS: Smoking and individual sociodemographic characteristics
      were gathered from the Third Korea National Health and Nutrition Examination
      Survey, 2005. The Carstairs index was derived for each area using the 2005 census
      data. The data were analysed using multilevel logistic regression models.
      RESULTS: After adjusting for age and marital status, low education and manual
      jobs were significantly associated with a higher likelihood of smoking. In
      addition, the effect of manual jobs on smoking was modified by area deprivation.
      When individual occupation and area deprivation were examined together, results
      indicated that women with manual occupation had much greater odds of smoking when
      they lived in the least-deprived areas (OR, 4.03; CI, 2.00 to 8.14) than did
      women with manual job who lived in the middle- or most-deprived areas (OR, 2.19;
      CI, 1.15 to 4.16), compared to the reference group (housewives in the middle- or
      most-deprived areas). CONCLUSION: The results of the present study show that
      among Korean women, manual work is associated with smoking, and the association
      is strongest among those living in the least-deprived areas. This interaction
      between manual work and area deprivation resulted in a higher smoking prevalence
      among women in affluent urban areas.

PMID- 20675690
TI  - Indoor smoking bans in Bulgaria, Croatia, Northern Cyprus, Romania and Turkey.
AB  - BACKGROUND: The purpose of this study was to examine attitudes towards attempts
      to limit second-hand smoke (SHS) in five Eastern European nations. METHODS: The
      data consist of a Eurobarometer (64.3) survey distributed from November to
      December 2005. Logistic regression was employed to investigate support levels for
      indoor smoking bans across the five political units. RESULTS: Across nations,
      there is more support for smoking bans in offices and indoor work spaces and
      indoor public space as opposed to restaurants and bars and pubs. Personal smoking
      behaviours are linked strongly with the smoking bans. Most importantly, it is
      specific knowledge about the health dangers of smoking which fosters support for
      indoor smoking bans. CONCLUSION: Policy implications suggest that government and
      the media must disseminate accurate information about the harm of smoking to
      broader segments of the population to gain support for policies that affect the
      dangers of SHS in these nations.

PMID- 20675692
TI  - The management of gastric polyps.
AB  - BACKGROUND: Gastric polyps are important as some have malignant potential. If
      such polyps are left untreated, gastric cancer may result. The malignant
      potential depends on the histological type of the polyp. The literature base is
      relatively weak and any recommendations made must be viewed in light of this.
      DEFINITION: Gastric polyps are sessile or pedunculated lesions that originate in
      the gastric epithelium or submucosa and protrude into the stomach lumen.
      MALIGNANT POTENTIAL: Depending on histological type, some gastric polyps
      (adenomas and hyperplastic polyps) have malignant potential and are precursors of
      early gastric cancer. They may also indicate an increased risk of intestinal or
      extra-intestinal malignancy.

PMID- 20675691
TI  - Serum fibrosis markers are associated with liver disease progression in non
      responder patients with chronic hepatitis C.
AB  - OBJECTIVES: The aim of this study was to explore the association of serum
      fibrosis marker levels with the risk of clinical and histological disease
      progression in a large cohort of patients with chronic hepatitis C (CHC).
      METHODS: 462 prior non-responders to peginterferon and ribavirin enrolled in the
      randomised phase of the Hepatitis C Antiviral Long-term Treatment against
      Cirrhosis (HALT-C) Trial had baseline and annual serum samples tested for
      hyaluronic acid (HA), N-terminal peptide of procollagen type 3, tissue inhibitor
      of matrix metalloproteinase-1 (TIMP-1) and YKL-40. All patients underwent a
      pretreatment liver biopsy and follow-up biopsies at years 2 and 4. Histological
      progression was defined as a >=2 point increase in Ishak fibrosis score in
      patients without cirrhosis. Clinical outcomes included development of
      decompensation, hepatocellular cancer, death or an increase in the CTP (Child
      Turcotte-Pugh) score to >=7. RESULTS: Mean patient age was 49.5 years and 39% had
      histological cirrhosis at entry. Baseline HA, YKL-40 and TIMP-1 levels combined
      with other laboratory parameters were all significantly associated with clinical
      outcomes in the 69 (15%) patients with disease progression (p<0.0001). The best
      multivariate model to predict clinical outcomes included baseline bilirubin,
      albumin, international normalised ratio (INR) and YKL-40 levels. All of the
      baseline serum fibrosis marker levels were also significantly associated with
      histological fibrosis progression that developed in 70 (33%) of the 209 patients
      with cirrhosis (p <0.0001). However, baseline HA and platelet counts were best at
      predicting histological progression (area under the curve (AUC)=0.663).
      CONCLUSION: Pretreatment serum fibrosis marker levels are significantly increased
      in patients with CHC at risk of clinical and histological disease progression. If
      validated in additional cohorts, measurement of these markers could help identify
      patients with CHC who would benefit from more frequent and intensive monitoring.

PMID- 20675693
TI  - Enhanced liver fibrosis test can predict clinical outcomes in patients with
      chronic liver disease.
AB  - BACKGROUND: Clinicians use fibrosis in a liver biopsy to predict clinical
      outcomes of chronic liver disease. The performance of non-invasive tests has been
      evaluated against histological assessment of fibrosis but use of clinical
      outcomes as the reference standard would be ideal. The enhanced liver fibrosis
      (ELF) test was derived and validated in a large cohort of patients and shown to
      have high diagnostic accuracy (area under the curve (AUC)=0.80 95% CI 0.76 to
      0.85) in identification of significant fibrosis on biopsy. OBJECTIVE: To evaluate
      ELF performance in predicting clinical outcomes by following up the original ELF
      cohort. METHODS: Patients recruited to the ELF study at seven English centres
      were followed up for liver morbidity and mortality by examination of clinical
      data. Defaulting/discharged patients were followed up by family practitioner
      questionnaires. Primary outcome measure was liver-related morbidity/liver-related
      death. RESULTS: 457 patients were followed up (median 7 years), with
      ascertainment of clinical status in 92%. There were 61 liver-related outcomes (39
      deaths). Survival analysis showed that the ELF score predicts liver outcomes,
      with people having the highest ELF scores being significantly more likely to have
      clinical outcomes than those in lower-score groups. A Cox proportional hazards
      model showed fully adjusted HRs of 75 (ELF score 12.52-16.67), 20 (10.426-12.51)
      and 5 (8.34-10.425) compared with patients with ELF <8.34. A unit change in ELF
      is associated with a doubling of risk of liver-related outcome. CONCLUSIONS: An
      ELF test can predict clinical outcomes in patients with chronic liver disease and
      may be a useful prognostic tool in clinical practice.

PMID- 20675694
TI  - Early features of acute-on-chronic alcoholic liver failure: a prospective cohort
      study.
AB  - BACKGROUND: 'Acute-on-chronic liver failure' (ACLF) is characterised in a more
      advanced stage by liver failure associated with multiple other end-organ failure.
      The global clinical characteristics of this entity remain, however, ill-defined.
      OBJECTIVE: To characterise and evaluate the clinicopathological features of
      patients with ACLF compared with patients with chronic decompensated cirrhosis
      (CHD) in a prospective, homogeneous cohort of patients with histologically proven
      alcoholic cirrhosis from 2002 to 2007. RESULTS: In total 250 patients were
      screened (ACLF (n=70, 28%) and CHD (n=180, 72%)). Alcoholic liver disease was
      observed in respectively 61/70 (87%) of patients with ACLF and 72/180 (40%) of
      patients with CHD. After exclusion of 31 patients, 102 patients were studied: 54
      with ACLF (median age 51 years; Child-Pugh 12+/-2; in-hospital mortality 46%
      (25/54)) and 48 patients with CHD (median age 53 years; Child-Pugh 10+/-2; in
      hospital mortality 10% (5/48)). In the patients with ACLF who survived the
      hospital stay, the difference in transplant-free survival compared with patients
      with CHD tended to attenuate with time. At admission the apparent infection of
      patient groups was comparable but during hospitalisation infection occurred more
      frequently in patients with ACLF (31/53 (58%)) than in those with CHD (12/47=26%)
      (p=0.007). Early signs of infection, positive systemic inflammatory response
      syndrome (SIRS) criteria at admission and ductular bilirubinostasis (p=0.04),
      were early features that predicted outcome in ACLF. CONCLUSION: Patients with
      ACLF have a high short-term mortality but those who survived the acute
      exacerbation show a long-term outcome comparable to that of patients with CHD.
      Infection is the most common cause of mortality in these patients. Positive SIRS
      criteria and ductular bilirubinostasis are early markers of ACLF and might allow
      more rapid identification of high-risk patients.

PMID- 20675695
TI  - Prevalence of occult hepatitis B infection in a highly endemic area for chronic
      hepatitis B: a study of a large blood donor population.
AB  - BACKGROUND AND AIMS: The aim of the present study was to determine the population
      prevalence of occult hepatitis B (OHB) infection and its clinical profile in a
      highly endemic area of chronic hepatitis B virus disease. METHODS: OHB was first
      identified by individual sample testing for hepatitis B surface antigen (HBsAg)
      followed by nucleic acid testing (NAT) and vice versa for 3044 (cohort 1, stored
      sera from donation within 1 year) and 9990 (cohort 2, prospective study) blood
      donors, respectively. OHB was confirmed meticulously by >=2 out of 3 tests with
      detectable hepatitis B virus (HBV) DNA using a sensitive standardised assay.
      Detailed serology and viral load in the serum and liver were studied. RESULTS:
      The prevalence of OHB was 0.13% (4/3044) and 0.11% (11/9967) for cohort 1 and 2,
      respectively. In cohort 2, 10 out of 11 OHB samples were positive for anti-HBc
      (hepatitis B core antigen) antibody (all were immunoglobulin G). Seven had
      detectable anti-HBs. The serum HBV DNA levels were extremely low (highest 14.1
      IU/ml). Of the six donors who underwent liver biopsies, all had normal liver
      biochemistry, extremely low liver HBV DNA (highest 6.21 copies/cell) and nearly
      normal liver histology. For those with viral sequence generation, none had the
      common HBsAg mutant G145R. CONCLUSIONS: The prevalence of OHB in a highly endemic
      area of chronic HBV was very low, thus implying a low impact on transfusion
      services. To implement universal screening, the high cost of NAT should be taken
      into account. OHB blood donors had very low HBV replication, and normal liver
      biochemistry and histology, conferring a favourable prognosis.

PMID- 20675696
TI  - Antitumoural immunity by virus-mediated immunogenic apoptosis inhibits metastatic
      growth of hepatocellular carcinoma.
AB  - BACKGROUND AND AIMS: Viral infection of a dying cell dictates the immune response
      against intracellular antigens, suggesting that virotherapy may be an effective
      tool to induce immunogenic cell death during systemic cancer treatment. Since
      viruses and proteasome inhibitors both induce accumulation of misfolded proteins,
      endoplasmic reticulum (ER) stress and immune responses during treatment of
      hepatocellular carcinoma (HCC) with bortezomib and the tumour-specifically
      replicating virus hTert-Ad (human telomerase reverse transcriptase promoter
      regulated adenovirus) were investigated. METHODS: Unfolded protein response (UPR)
      pathways and ER stress-mediated apoptosis were investigated by western blots,
      caspase-3 assays, 4',6-diamidino-2-phenylindole (DAPI) and Annexin V staining in
      HCC cells following hTert-Ad/bortezomib treatment. Oncolysis was assessed in
      subcutaneous HCC mouse models. Antiviral/antitumoural immune responses were
      characterised in immunocompetent HCC mouse models by ELISA, ELISpot assays and
      pentamer staining. Systemic efficacy of antitumoural immunity was investigated by
      determination of lung metastases burden. RESULTS: Bortezomib and hTert-Ad trigger
      complementary UPR pathways but negatively interfere with important recovery
      checkpoints, resulting in enhanced apoptosis of HCC cells in vitro and improved
      oncolysis in vivo. In immunocompetent mice, bortezomib inhibited antiviral immune
      responses, whereas ER stress-induced apoptosis of infected HCC resulted in
      caspase-dependent triggering of antitumoural immunity. In therapeutic settings in
      immunocompetent, but not in immunodeficient or CD8-depleted mice, virotherapy
      induced antitumoural immunity efficiently inhibited outgrowth of non-infected
      lung metastases. Immunotherapeutic efficacy could be significantly improved by
      bortezomib in experiments with low viral doses. CONCLUSION: Proteasome inhibition
      during virotherapy disrupts the UPR, leading to enhanced ER stress-induced
      apoptosis, improved local oncolysis and antitumoural immunity. The results
      suggest that combining intratumoural virotherapy with adjuvant systemic
      therapies, which specifically support the function of the virotherapy as an
      antitumoural vaccine, is a promising immunotherapeutic strategy against HCC.

PMID- 20675698
TI  - Use of gelofusine for endoscopic mucosal resection.

PMID- 20675697
TI  - Activation of brain macrophages/microglia cells in hepatitis C infection.
AB  - OBJECTIVES: Hepatitis C virus (HCV) infection is commonly associated with
      cognitive dysfunction. Viral sequences and proteins were previously found in
      brain macrophage/microglia cells. The aim of the current study was to determine
      whether HCV infection affects the expression of key cytokines and chemokines in
      these cells. METHODS: Autopsy brain tissue from 15 patients was studied; 7
      patients were HCV positive and 8 were HCV negative. Cryostat sections of frontal
      cortex and subcortical white matter were stained with monoclonal antibodies
      specific for microglia/macrophages (anti-CD68) and separated by laser capture
      microscopy. Transcripts representing 25 various cytokines and chemokines were
      measured by real-time quantitative PCR. RESULTS: Compared with HCV-negative
      controls, HCV-positive patients demonstrated significantly higher levels of
      proinflammatory cytokines interleukin 1alpha (IL-1alpha), IL-1beta, tumour
      necrosis factor alpha (TNFalpha), IL-12 and IL-18. HCV infection was also
      associated with increased transcription of chemokines IL-8, IL-16 and interferon
      inducible protein 10 (IP-10). Type 1 interferon (IFN) activation was suggested by
      increased concentrations of IFNbeta and myxovirus resistance protein A (MxA)
      transcripts. Similar results were obtained when CD68-positive/HCV-positive cells
      were compared with CD68-positive/HCV-negative cells in each of the 7 HCV-infected
      patients. CONCLUSION: Evidence was found for activation of brain
      macrophages/microglia cells in autopsy brain tissue from HCV-positive patients.
      These findings could relate to the common presence of neurocognitive dysfunction
      among patients with chronic hepatitis C.

PMID- 20675699
TI  - Toll-like receptors 2/4 agonists: a potential strategy for preventing invasion
      and metastasis of hepatocellular carcinoma.

PMID- 20675700
TI  - New MRI modalities for assessment of inflammatory bowel disease.

PMID- 20675702
TI  - Socioeconomic status and diabetes-related hospital admissions: a cross-sectional
      study of people with diagnosed diabetes.
AB  - BACKGROUND: Low socioeconomic status (SES) is associated with adverse
      cardiovascular risk factor patterns and poorer outcomes for people with diabetes.
      METHODS: A cross-sectional study was performed using data for 35,925 people with
      diagnosed diabetes in Scotland and an area-based measure of SES using linked
      hospital and population-based diabetes register records. Comparisons by quintile
      of SES were made before (with p values presented for trend across quintiles given
      below) and after adjusting for other factors using multivariable logistic
      regression. RESULTS: People in the most deprived quintile were more likely than
      people in the most affluent quintile to have hospital records for diabetic kidney
      disease (2.4% vs 2.0%, p=0.049), diabetic ketoacidosis (3.5% vs 3.0%, p=0.11),
      hypoglycaemia (1.8% vs 1.4%, p=0.008), ischaemic heart disease (22% vs 17%,
      p<0.0001), stroke (6.8% vs 5.1%, p<0.0001) and peripheral arterial disease (4.1%
      vs 2.1%, p<0.0001). An independent effect of SES persisted for cardiovascular
      disease outcomes after adjusting for age and sex. There were minimal differences
      in disease management measures by SES. CONCLUSION: Managing current risk factors
      equitably is unlikely to remove socioeconomic inequalities in diabetes-related
      outcomes. Measures of SES may be valuable in risk scores and in making valid
      comparisons of the quality of diabetes care.

PMID- 20675701
TI  - Do different measures of early life socioeconomic circumstances predict adult
      mortality? Evidence from the British Whitehall II and French GAZEL studies.
AB  - BACKGROUND: Father's occupational position, education and height have all been
      used to examine the effects of adverse early life socioeconomic circumstances on
      health, but it remains unknown whether they predict mortality equally well.
      METHODS: We used pooled data on 18,393 men and 7060 women from the Whitehall II
      and GAZEL cohorts to examine associations between early life socioeconomic
      circumstances and all-cause and cause-specific mortality. RESULTS: During the 20
      y follow-up period, 1487 participants died. Education had a monotonic association
      with all mortality outcomes; the age, sex and cohort-adjusted HR for the lowest
      versus the highest educational group was 1.45 (95% CI 1.24 to 1.69) for all-cause
      mortality. There was evidence of a U-shaped association between height and all
      cause, cancer and cardiovascular mortality robust to adjustment for the other
      indicators (HR 1.41, 95% CI 1.03 to 1.93 for those shorter than average and HR
      1.36, 95% CI 0.98 to 1.88 for those taller than average for cardiovascular
      mortality). Greater all-cause and cancer mortality was observed in participants
      whose father's occupational position was manual rather than non-manual (HR 1.11,
      95% CI 1.00 to 1.23 for all-cause mortality), but the risks were attenuated after
      adjusting for education and height. CONCLUSIONS: The association between early
      life socioeconomic circumstances and mortality depends on the socioeconomic
      indicator used and the cause of death examined. Height is not a straightforward
      measure of early life socioeconomic circumstances as taller people do not have a
      health advantage for all mortality outcomes.

PMID- 20675703
TI  - Comparison of methods for modelling a count outcome with excess zeros:
      application to Activities of Daily Living (ADL-s).
AB  - BACKGROUND: Count outcomes are commonly encountered in many epidemiology
      applications, and are often characterised by a large proportion of zeros.
      Although linear or logistic regression models have often been used to analyse
      count outcomes, the resulting estimates are likely to be inefficient,
      inconsistent or biased. METHODS: Data were taken from the first wave of the
      English Longitudinal Study of Ageing (ELSA). The main outcome measure is
      difficulty (ranging from 0 to 6) with 'Activities of Daily Living (ADL-s)', such
      as dressing, walking across a room, bathing, eating, getting in and out of bed
      and using the toilet. Four regression models specifically developed for count
      outcomes were fitted to the data: Poisson, negative binomial (NB), zero-inflated
      Poisson (ZIP) and zero-inflated negative binomial (ZINB). The models were
      compared using the Likelihood Ratio (LR) test of overdispersion, the Vuong test
      and graphical methods. RESULTS: The plots of predictions showed that overall, the
      ZINB model fit best. Although the ZINB and the ZIP models showed similar fit, the
      LR test provided strong evidence that the ZINB had improved fit over the ZIP.
      Increasing difficulties with ADL-s were associated with fair/poor self-reported
      health, limiting longstanding illness and physical inactivity. The probability of
      not having any difficulty with ADL-s decreases with a limiting longstanding
      illness, increasing age, no education, fair/poor self-reported health and with
      not living with a partner. CONCLUSION: Models specifically developed for count
      outcomes with excess zeros such as ZINB can provide better insights into the
      investigation of the factors associated with the difficulties with ADL-s.

PMID- 20675704
TI  - Health inequalities in Europe: new insights from European Labour Force Surveys.
AB  - BACKGROUND: Socio-economic inequalities in health have become a major public
      health concern in Europe. The measurement of health inequalities over time and
      across countries does, however, remain a challenge. Previous European evidence
      found that health inequalities have been increasing in most countries, with
      greatly varying degrees. METHODS: The authors use the European Labour Force
      Survey (ELFS), with its unprecedented coverage of years and countries, as a
      potential complementary source for the measurement of health inequality. The ELFS
      provides information on sickness absence or reduced labour supply attributable to
      ill health. After constructing four separate and one overall health indicator,
      the authors compute health inequality indices for all countries and years, and
      analyse their trends. The authors also examine the sensitivity of the health
      inequality measures to different proxies of socio-economic status and. RESULTS:
      Health inequalities in the working age population have been increasing for
      several countries, but also decreasing in about as many countries, while they
      remained stable in a minority of countries. These results are not too sensitive
      to the various proxies for socio-economic status we employ, but they are
      sensitive to the specific health indicator from which the inequality index is
      derived. CONCLUSIONS: While not without its problems, the ELFS may offer a useful
      additional and hitherto unexploited resource for the measurement of socio
      economic inequalities in health across European countries and over time. Future
      research should try to understand how and why health inequality trends differ
      between different surveys as much as they appear to do in light of the present
      findings.

PMID- 20675705
TI  - Sleep disturbance and daytime sleepiness predict vascular dementia.
AB  - BACKGROUND: Disturbed sleep is common throughout the community and is associated
      with an increase in daytime sleepiness, both of which, in turn are associated
      with an increased risk of ischaemic vascular disease. The hypothesis that sleep
      disturbances are predictive of dementia, and in particular vascular dementia was
      tested in a large community-based cohort of older men. METHODS: A questionnaire
      on sleep disturbances was administered to 1986 men aged 55-69 years in the
      Caerphilly Cohort Study and 10 years later the men were examined clinically for
      evidence of dementia or cognitive impairment with no dementia (CIND). FINDINGS:
      Approximately 20% of the men reported disturbed sleep and 30% reported 'severe'
      daytime sleepiness. Ten years later 1,225 men (75% of the surviving men in the
      cohort) were tested and 268 (22%) were found to be cognitively impaired with 93
      (7.6%) showing clear evidence of dementia and the remaining 175 (14.3%) showing
      evidence of CIND. After adjustment for possible confounding, including cognitive
      function and the taking of sleeping tablets at baseline, sleep disturbances
      appeared to be predictive of dementia and CIND of vascular origin, while there
      was no suggestion of prediction of non-vascular cognitive impairment by sleep.
      Prediction of vascular dementia appeared to be particularly strong for daytime
      sleepiness, with an adjusted OR of 4.44 (95% CI 2.05 to 9.61). Further
      adjustments for psychological distress at baseline reduced the size of the
      relationships, but the ORs remain large, consistent with a direct positive effect
      of sleep disturbance on vascular dementia. INTERPRETATION: Sleep disturbances,
      and in particular severe daytime sleepiness, appear to be strongly predictive of
      vascular dementia, but have no predictive power for non vascular dementia.

PMID- 20675706
TI  - Anti-TNF therapy is associated with an increased risk of serious infections in
      patients with rheumatoid arthritis especially in the first 6 months of treatment:
      updated results from the British Society for Rheumatology Biologics Register with
      special emphasis on risks in the elderly.
AB  - OBJECTIVES: To evaluate the risk of serious infections (SIs) in patients with RA
      treated with anti-TNF therapy with emphasis on the risk across different ages.
      METHODS: Using data from the British Society for Rheumatology Biologics Register,
      a prospective observational study, we compared the risk of SI between 11 798 anti
      TNF-treated patients and 3598 non-biologic DMARD (nbDMARD)-treated patients.
      RESULTS: A total of 1808 patients had at least one SI (anti-TNF: 1512; nbDMARD:
      296). Incidence rates were: anti-TNF 42/1000 patient-years of follow-up (95% CI
      40, 44) and nbDMARD 32/1000 patient-years of follow-up (95% CI 28, 36). The
      adjusted hazard ratio (adjHR) for SI in the anti-TNF cohort was 1.2 (95% CI 1.1,
      1.5). The risk did not differ significantly between the three agents adalimumab,
      etanercept and infliximab. The risk was highest during the first 6 months of
      therapy [adjHR 1.8 (95% CI 1.3, 2.6)]. Although increasing age was an independent
      risk factor for SI in both cohorts, there was no difference in relative risk of
      infection in patients on anti-TNF therapy in the older population. There was no
      difference in hospital stay for SI between cohorts. Mortality within 30 days of
      SI was 50% lower in the anti-TNF cohort [odds ratio 0.5 (95% CI 0.3, 0.8)].
      CONCLUSIONS: These data add to currently available evidence suggesting that anti
      TNF therapy is associated with a small but significant overall risk of SI. This
      must be balanced against the risks associated with poor disease control or
      alternative treatments.

PMID- 20675708
TI  - Predictors at diagnosis of a first Wegener's granulomatosis relapse after
      obtaining complete remission.
AB  - OBJECTIVE: Although in most patients with WG, induction therapy leads to complete
      remission (CR), the high relapse rate remains a major problem. This study was
      undertaken to identify potential predictors of these relapses. METHODS: WG
      outcomes of patients included in two randomized trials were analysed. Patients
      were categorized into a predominant form of the disease using a scoring system
      composed of three granulomatous criteria (ear, nose and throat manifestations;
      lung nodules; and orbital pseudotumour) and three vascular criteria (serum
      creatinine >125 umol/l, haematuria or proteinuria and alveolar haemorrhage).
      RESULTS: Among 174 patients, 152 (87%) entered CR with CSs and CYC. The risk of
      death was higher for the vascular form [odds ratio (OR) 3.5 (95% CI 1.1, 11.4)].
      With a median follow-up of 50 months, 66 out of 152 patients experienced a
      relapse (5-year relapse rate: 49%). Multivariate analysis retained the following
      variables at diagnosis as independent predictors of relapse: specific cardiac
      involvement [hazard ratio (HR) 2.9 (95% CI 1.3, 6.5)], ANCA with cytoplasmic
      labelling pattern (c-ANCA) [HR 2.1 (95% CI 1.1, 4.3)] and higher age [HR 1.4 (95%
      CI 1.1, 1.7)]. Conversely, severe renal insufficiency was associated with a lower
      relapse rate [HR 0.4 (95% CI, 0.2-0.8)]. Comparing predominant granulomatous vs
      predominant vascular disease, relapses were more frequent and earlier with
      decreasing risk over time. CONCLUSIONS: Increased risk of first WG relapse after
      initial remission appears to be related to heart involvement, age and c-ANCA
      positivity at onset. Predominant granulomatous presentation disease seems to be
      associated with poorer outcomes after CR. These findings may help adapt treatment
      strategies.

PMID- 20675707
TI  - Occupational and environmental exposures and risk of systemic lupus
      erythematosus: silica, sunlight, solvents.
AB  - OBJECTIVES: We examined occupational and non-occupational exposures in relation
      to risk of SLE in a case-control study conducted through the Canadian Network for
      Improved Outcomes in SLE (CaNIOS). METHODS: SLE cases (n = 258) were recruited
      from 11 rheumatology centres across Canada. Controls (without SLE, n = 263) were
      randomly selected from phone number listings and matched to cases by age, sex and
      area of residence. Data were collected using a structured telephone interview.
      RESULTS: An association was seen with outdoor work in the 12 months preceding
      diagnosis [odds ratio (OR) 2.0; 95% CI 1.1, 3.8]; effect modification by sun
      reaction was suggested, with the strongest effect among people who reported
      reacting to midday sun with a blistering sunburn or a rash (OR 7.9; 95% CI 0.97,
      64.7). Relatively strong but imprecise associations were seen with work as an
      artist working with paints, dyes or developing film (OR 3.9; 95% CI 1.3, 12.3)
      and work that included applying nail polish or nail applications (OR 10.2; 95% CI
      1.3, 81.5). Patients were more likely than controls to report participation in
      pottery or ceramics work as a leisure activity, with an increased risk among
      individuals with a total frequency of at least 26 days (OR 2.1; 95% CI 1.1, 3.9).
      Analyses of potential respirable silica exposures suggested an exposure-response
      gradient (OR 1.0, 1.4. and 2.1 for zero, one and two or more sources of exposure,
      respectively; trend test P < 0.01). CONCLUSIONS: This study supports the role of
      specific occupational and non-occupational exposures in the development of SLE.

PMID- 20675709
TI  - Influence of myeloperoxidase by anti-myeloperoxidase antibodies and its
      association with the disease activity in microscopic polyangiitis.
AB  - OBJECTIVES: ANCAs with specificity for MPO are serological markers of ANCA
      associated vasculitides, especially microscopic polyangiitis (MPA). This study
      investigated potential associations between the influence of MPO-ANCA on the
      oxidation activity of MPO and the clinical manifestations as well as
      immunological characteristics of MPO-ANCA. METHODS: MPO-ANCA was purified with
      MPO-affinity chromatography from plasma of 13 consecutive patients with MPO-ANCA
      positive MPA. The titre, avidity, immunoglobulin G (IgG) subclasses and the
      ability to reverse the binding between ceruloplasmin and MPO of MPO-ANCA were
      tested using ELISA. The oxidation activity of MPO in the presence of MPO-ANCA was
      measured. The associations between the oxidation activity of MPO after binding
      MPO-ANCA and the clinical and immunological characteristics of MPO-ANCA were
      analysed. RESULTS: The MPO activity without binding to its autoantibodies was
      1.521 (0.12) (expressed by A-values at 10 min, using o-phenylenediamine as
      substrate). After binding affinity-purified MPO-ANCA, the MPO activity ranged
      from 1.083 to 1.642. Correlation analysis showed that the oxidation activity of
      MPO after binding MPO-ANCA positively correlated with the level of ceruloplasmin
      binding on MPO in presence of MPO-ANCA (r = 0.617, P = 0.025) and negatively
      correlated with initial sera creatinine levels (r = -0.564, P = 0.045), BVAS (r =
      -0.735, P = 0.004), avidity of MPO-ANCA (r = -0.575, P = 0.040), levels of IgG2
      (r = -0.610, P = 0.027) and IgG3 subclasses (r = -0.695, P = 0.008) of MPO-ANCA.
      CONCLUSIONS: MPO-ANCA from different patients can influence MPO activity with
      different levels. The low oxidation activity of MPO after binding MPO-ANCA might
      be associated with more severe disease.

PMID- 20675710
TI  - Impact of Behcet's syndrome on health-related quality of life: influence of the
      type and number of symptoms.
AB  - OBJECTIVE: To assess the overall impact of Behcet's syndrome (BS) on quality of
      life and the specific impact of the type and number of symptoms on the quality of
      life of adults with BS. METHODS: A questionnaire was mailed to the 641 adult
      members of the Behcet's Syndrome Society in the UK. Participants provided
      information on socio-demographic characteristics, disease duration, current
      symptoms (mouth ulcers, genital ulcers, skin lesions, fatigue, joint problems,
      stomach/bowel problems, eye problems, pathergy reaction, headaches and other
      neurological problems), symptom control and quality of life (the EQ-5D index).
      Linear regression was used to test the associations of the type and number of
      symptoms with the EQ-5D index. RESULTS: Of the 447 members, 400 who returned the
      questionnaires had a confirmed diagnosis of BS. Of them, 362 had information on
      the variables selected for this analysis (76% females and 94% white British). The
      mean EQ-5D index was 0.47 (S.D. 0.38). Of the 10 symptoms assessed, joint
      problems had the strongest impact on quality of life, followed by neurological
      problems, pathergy reaction and stomach/bowel problems (adjusted coefficients of 
      0.15, -0.13, -0.11 and -0.18, respectively). Furthermore, the number of symptoms
      was significantly related to the EQ-5D index after adjustment for socio
      demographic characteristics, disease duration and symptom control. The EQ-5D
      index decreased by -0.05 U for every additional symptom reported. CONCLUSIONS: BS
      has a considerable impact on quality of life. Both the type and number of
      symptoms affect the quality of life of adults with BS.

PMID- 20675711
TI  - The p-control chart: a tool for care improvement.
AB  - BACKGROUND: The p-chart is a user-friendly tool for monitoring adverse events. By
      converting data into knowledge, it is helpful in interpreting and reducing
      sources of variability in care. Certain basics for developing expertise to use p
      charts correctly are necessary. PURPOSE: This paper provides key elements on how
      to develop and interpret a p-chart for clinical practice, how to successfully
      integrate this tool within a comprehensive approach, and how to report a study
      based on p-chart utilization. P-chart building The p-chart combines time series
      analysis with a graphical presentation of data by plotting successive indicator
      measurements in chronological order. The pragmatic choice of well-defined
      indicators to be monitored is essential. Exact control limits based on the
      binomial distribution and the incorporation of risk adjustment represent
      important contributions for further improving the tool's performance in health
      care settings. P-chart implementation The solution needed to reduce adverse
      events is not available from measurement alone. The success of routine
      introduction of the p-chart requires investigation of the causes of indicator
      variations and the trying out of quality improvement initiatives. It must be
      supported by strong management leadership within an atmosphere of constructive
      evaluation. Perspectives The implementation of the p-chart into clinical practice
      encourages practitioners to continuously undertake a critical examination of the
      care delivered. Nearly a century after it was created in the manufacturing
      industry, the control chart now contributes to improving the quality of health
      care processes and patient safety.

PMID- 20675712
TI  - The perception of quinine taste intensity is associated with common genetic
      variants in a bitter receptor cluster on chromosome 12.
AB  - The perceived taste intensities of quinine HCl, caffeine, sucrose octaacetate
      (SOA) and propylthiouracil (PROP) solutions were examined in 1457 twins and their
      siblings. Previous heritability modeling of these bitter stimuli indicated a
      common genetic factor for quinine, caffeine and SOA (22-28%), as well as separate
      specific genetic factors for PROP (72%) and quinine (15%). To identify the genes
      involved, we performed a genome-wide association study with the same sample as
      the modeling analysis, genotyped for approximately 610,000 single-nucleotide
      polymorphisms (SNPs). For caffeine and SOA, no SNP association reached a genome
      wide statistical criterion. For PROP, the peak association was within TAS2R38
      (rs713598, A49P, P = 1.6 * 10(-104)), which accounted for 45.9% of the trait
      variance. For quinine, the peak association was centered in a region that
      contains bitter receptor as well as salivary protein genes and explained 5.8% of
      the trait variance (TAS2R19, rs10772420, R299C, P = 1.8 * 10(-15)). We confirmed
      this association in a replication sample of twins of similar ancestry (P =
      0.00001). The specific genetic factor for the perceived intensity of PROP was
      identified as the gene previously implicated in this trait (TAS2R38). For
      quinine, one or more bitter receptor or salivary proline-rich protein genes on
      chromosome 12 have alleles which affect its perception but tight linkage among
      very similar genes precludes the identification of a single causal genetic
      variant.

PMID- 20675713
TI  - Fukutin-related protein is essential for mouse muscle, brain and eye development
      and mutation recapitulates the wide clinical spectrums of dystroglycanopathies.
AB  - Mutations in fukutin-related protein (FKRP) cause a common subset of muscular
      dystrophies characterized by aberrant glycosylation of alpha-dystroglycan (alpha
      DG), collectively known as dystroglycanopathies. The clinical variations
      associated with FKRP mutations range from mild limb-girdle muscular dystrophy
      type 2I with predominantly muscle phenotypes to severe Walker-Warburg syndrome
      and muscle-eye-brain disease with striking structural brain and eye defects. In
      the present study, we have generated animal models and demonstrated that ablation
      of FKRP functions is embryonic lethal and that the homozygous-null embryos die
      before reaching E12.5. The homozygous knock-in mouse carrying the missense P448L
      mutation almost completely lacks functional glycosylation of alpha-DG in muscles
      and brain, validating the essential role of FKRP in the functional glycosylation
      of alpha-DG. However, the knock-in mouse survives and develops a wide range of
      structural abnormalities in the central nervous system, characteristics of
      neuronal migration defects. The brain and eye defects are highly reminiscent of
      the phenotypes seen in severe dystroglycanopathy patients. In addition, skeletal
      muscles develop progressive muscular dystrophy. Our results confirm that post
      translational modifications of alpha-DG are essential for normal development of
      the brain and eyes. In addition, both the mutation itself and the levels of FKRP
      expression are equally critical for the survival of the animals. The
      exceptionally wide clinical spectrums recapitulated in the P448L mice also
      suggest the involvement of other factors in the disease progression. The mutant
      mouse represents a valuable model to further elucidate the functions of FKRP and
      develop therapies for FKRP-related muscular dystrophies.

PMID- 20675714
TI  - From knowledge to planning considerations: a matrix to assess health needs for
      the perinatal network in eastern Paris.
AB  - BACKGROUND: Regionalization of perinatal care is required throughout networks to
      reduce perinatal morbidity and mortality and to organize access to health
      services for high-risk new borns, such as in the eastern Paris in 2007. Our study
      sought to design a matrix to build a perinatal knowledge base for assessing
      health needs and facilitating public health planning process for the perinatal
      network in eastern Paris. METHODS: Our matrix listed as its columns 'perinatal
      stages' from conception through the age of 6 years, whereas the rows covered
      components related to public health planning (i.e. target population, perinatal
      risk factors and health services). For each situation, the matrix lists require
      information and potential data sources to measure health status and health
      services. RESULTS: Our matrix structures the cyclical process for building
      knowledge for action. The eastern Paris has a population of 670,000. Its nine
      maternity units are distributed into three levels of care, a level-3 unit opened
      up in June 2007. A total of 16,400 deliveries occur every year in the nine units;
      2500 women living in the eastern area deliver outside the area. CONCLUSION: Our
      matrix is useful for building a comprehensive perinatal knowledge base depending
      upon perinatal stages and health-care dimensions. It should imply stakeholders in
      collecting, synthesizing and analysing massive amounts of data. It can be adapted
      to any health network or local health policy.

PMID- 20675715
TI  - Isoform-specific roles of protein phosphatase 1 catalytic subunits in
      sarcoplasmic reticulum-mediated Ca(2+) cycling.
AB  - AIMS: protein phosphatase 1 (PP1) is the major isotype of serine/threonine
      phosphatase in cardiomyocytes, and its activity has been thought to be important
      for heart failure progression. The PP1 catalytic subunits consist of three
      distinct genes, PP1alpha, PP1beta/delta, and PP1gamma. To date, the function of
      each PP1 isoform is not well characterized in cardiomyocytes. We sought to
      determine the functional contribution of each PP1 isoform to sarcoplasmic
      reticulum (SR)-mediated Ca(2+) cycling in isolated adult rat cardiomyocytes.
      METHODS AND RESULTS: adenoviral vectors encoding short hairpin RNA for each PP1
      isoform were transfected into isolated rat cardiomyocytes, and this was followed
      by analysis of cell shortening, Ca(2+) transients, and the phosphorylation levels
      of Ca(2+) regulatory proteins. Physical interactions between each PP1 isoform and
      SR Ca(2+) regulatory proteins were characterized in isolated cardiomyocytes
      expressing green fluorescent protein (GFP)-tagged PP1 catalytic subunits, and
      also in canine junctional and longitudinal SR preparations. Successful PP1
      isoform knockdown was achieved for each isoform without affecting the expression
      of the other isoforms. PP1beta knockdown most significantly enhanced the Ca(2+)
      transient and cell shortening by augmenting phospholamban (PLN) phosphorylation
      at baseline and with low-dose isoproterenol stimulation (10 nM). Interestingly,
      PP1beta was preferentially associated with sarco-endoplasmic ATPase and PLN in
      GFP-PP1-transfected cardiomyocytes, as well as in canine longitudinal SR
      preparations. CONCLUSION: these findings indicate that PP1beta is the most
      significant PP1 isoform involved in regulating SR Ca(2+) cycling in rat
      cardiomyocytes.

PMID- 20675716
TI  - Assessing the nutritional status of Palestinian adolescents from East Jerusalem:
      a school-based study 2002-03.
AB  - In Palestine, there is a little information about nutrition of adolescents
      compared to other age groups. This study was designed to assess the nutritional
      status of Palestinian school-aged children (11-16 years) in East Jerusalem during
      2002-03. A school-based cross-sectional study targeted randomly 313 adolescents
      from public and private schools. A previously validated and reliable
      questionnaire was administered through interviews that included anthropometric
      and hemoglobin measurements, 24-h dietary intake recall and physical activity
      questionnaire. It was found that being overweight (24.3%) or obese (9.9%)
      coexisted with being underweight (4.8%) and/or anemic (23.3%). Only 22.4% of the
      study subject had physical activity for >=5 days a week with boys being more
      physically active than girls (p < 0.01). Inadequate energy intake had 55.66% of
      boys and 64.81% of girls; inadequate protein intake was reported by 15.07% of
      boys and 43.08% of girls. The majority of them met <80% of the recommended daily
      allowances for most micronutrients. The whole sample and especially boys consumed
      more total, saturated fat, less monounsaturated fat and carbohydrates than what
      is advised. Obese and overweight adolescents had lower energy intake (p < 0.05)
      and a lower trend in being physically active than normal weight counterparts.
      School health education programs targeted at adolescents and parents need to be
      developed as part of overweight-obesity, malnutrition and anemia prevention.

PMID- 20675717
TI  - Hepatoportal sclerosis and extrahepatic portal venous obstruction associated with
      anti-phospholipid antibody syndrome in child.
AB  - We report a 2-year-old child with extrahepatic portal venous obstruction,
      hepatoportal sclerosis and pulmonary thromboembolism whose sole
      hypercoagulability factor was the presence of anti-phospholipid antibodies.

PMID- 20675718
TI  - Cohort profile: the Nordic Perinatal Bereavement Cohort.

PMID- 20675719
TI  - Dynamics of a novel centromeric histone variant CenH3 reveals the evolutionary
      ancestral timing of centromere biogenesis.
AB  - The centromeric histone H3 variant (CenH3) serves to target the kinetochore to
      the centromeres and thus ensures correct chromosome segregation during mitosis
      and meiosis. The Dictyostelium H3-like variant H3v1 was identified as the CenH3
      ortholog. Dictyostelium CenH3 has an extended N-terminal domain with no
      similarity to any other known proteins and a histone fold domain at its C
      terminus. Within the histone fold, alpha-helix 2 (alpha2) and an extended loop 1
      (L1) have been shown to be required for targeting CenH3 to centromeres. Compared
      to other known and putative CenH3 histones, Dictyostelium CenH3 has a shorter L1,
      suggesting that the extension is not an obligatory feature. Through ChIP analysis
      and fluorescence microscopy of live and fixed cells, we provide here the first
      survey of centromere structure in amoebozoa. The six telocentric centromeres were
      found to mostly consist of all the DIRS-1 elements and to associate with H3K9me3.
      During interphase, the centromeres remain attached to the centrosome forming a
      single CenH3-containing cluster. Loading of Dictyostelium CenH3 onto centromeres
      occurs at the G2/prophase transition, in contrast to the anaphase/telophase
      loading of CenH3 observed in metazoans. This suggests that loading during
      G2/prophase is the ancestral eukaryotic mechanism and that anaphase/telophase
      loading of CenH3 has evolved more recently after the amoebozoa diverged from the
      animal linage.

PMID- 20675720
TI  - HEXIM1 targets a repeated GAUC motif in the riboregulator of transcription 7SK
      and promotes base pair rearrangements.
AB  - 7SK snRNA, an abundant RNA discovered in human nucleus, regulates transcription
      by RNA polymerase II (RNAPII). It sequesters and inhibits the transcription
      elongation factor P-TEFb which, by phosphorylation of RNAPII, switches
      transcription from initiation to processive elongation and relieves pauses of
      transcription. This regulation process depends on the association between 7SK and
      a HEXIM protein, neither isolated partner being able to inhibit P-TEFb alone. In
      this work, we used a combined NMR and biochemical approach to determine 7SK and
      HEXIM1 elements that define their binding properties. Our results demonstrate
      that a repeated GAUC motif located in the upper part of a hairpin on the 5'-end
      of 7SK is essential for specific HEXIM1 recognition. Binding of a peptide
      comprising the HEXIM Arginine Rich Motif (ARM) induces an opening of the GAUC
      motif and stabilization of an internal loop. A conserved proline-serine sequence
      in the middle of the ARM is shown to be essential for the binding specificity and
      the conformational change of the RNA. This work provides evidences for a
      recognition mechanism involving a first event of induced fit, suggesting that 7SK
      plasticity is involved in the transcription regulation.

PMID- 20675721
TI  - The role of transcription factories-mediated interchromosomal contacts in the
      organization of nuclear architecture.
AB  - Using numerical simulations, we investigate the underlying physical effects
      responsible for the overall organization of chromosomal territories in interphase
      nuclei. In particular, we address the following three questions: (i) why are
      chromosomal territories with relatively high transcriptional activity on average,
      closer to the centre of cell's nucleus than those with the lower activity? (ii)
      Why are actively transcribed genes usually located at the periphery of their
      chromosomal territories? (iii) Why are pair-wise contacts between active and
      inactive genes less frequent than those involving only active or only inactive
      genes? We show that transcription factories-mediated contacts between active
      genes belonging to different chromosomal territories are instrumental for all
      these features of nuclear organization to emerge spontaneously due to entropic
      effects arising when chromatin fibres are highly crowded.

PMID- 20675722
TI  - DNA compaction by the higher-order assembly of PRH/Hex homeodomain protein
      oligomers.
AB  - Protein self-organization is essential for the establishment and maintenance of
      nuclear architecture and for the regulation of gene expression. We have shown
      previously that the Proline-Rich Homeodomain protein (PRH/Hex) self-assembles to
      form oligomeric complexes that bind to arrays of PRH binding sites with high
      affinity and specificity. We have also shown that many PRH target genes contain
      suitably spaced arrays of PRH sites that allow this protein to bind and regulate
      transcription. Here, we use analytical ultracentrifugation and electron
      microscopy to further characterize PRH oligomers. We use the same techniques to
      show that PRH oligomers bound to long DNA fragments self-associate to form highly
      ordered assemblies. Electron microscopy and linear dichroism reveal that PRH
      oligomers can form protein-DNA fibres and that PRH is able to compact DNA in the
      absence of other proteins. Finally, we show that DNA compaction is not sufficient
      for the repression of PRH target genes in cells. We conclude that DNA compaction
      is a consequence of the binding of large PRH oligomers to arrays of binding sites
      and that PRH is functionally and structurally related to the Lrp/AsnC family of
      proteins from bacteria and archaea, a group of proteins formerly thought to be
      without eukaryotic equivalents.

PMID- 20675724
TI  - Sequential epiretinal membrane removal with internal limiting membrane peeling in
      brilliant blue G-assisted macular surgery.
AB  - PURPOSE: To assess the selectivity of brilliant blue G (BBG) staining by
      analysing the morphological components of unstained and stained tissue obtained
      during epiretinal membrane (ERM) removal with internal limiting membrane (ILM)
      peeling in BBG-assisted macular surgery. METHODS: Twenty-six surgical specimens
      were removed from 13 eyes with epiretinal gliosis during vitrectomy using BBG for
      ERM and ILM peeling. We included eyes with idiopathic macular pucker, idiopathic
      macular hole and vitreomacular traction syndrome. The dye was injected into the
      fluid-filled globe. Unstained and stained epiretinal tissue was harvested
      consecutively and placed into separate containers. All specimens were processed
      for conventional transmission electron microscopy. RESULTS: The first surgical
      specimen of all eyes showed no intraoperative staining with BBG and corresponded
      to masses of cells and collagen. The second surgical specimen demonstrated good
      staining characteristics and corresponded to the ILM in all patients included. In
      seven eyes, the ILM specimens were seen with minor cell proliferations such as
      single cells or a monolayer of cells. Myofibroblasts, fibroblasts and astrocytes
      were present. In five cases, native vitreous collagen fibrils were found at the
      ILM. In six of the eyes, ILM specimens were blank. CONCLUSION: Our
      clinicopathological correlation underlines the selective staining properties of
      BBG. The residual ILM is selectively stained by BBG even when a small amount of
      cells and collagen adheres to its vitreal side. To reduce the retinal exposure to
      the dye, the surgeon might choose to remove the ERM without using the dye,
      followed by a BBG injection to identify residual ILM.

PMID- 20675723
TI  - A domain insertion in Escherichia coli GyrB adopts a novel fold that plays a
      critical role in gyrase function.
AB  - DNA topoisomerases manage chromosome supercoiling and organization in all forms
      of life. Gyrase, a prokaryotic heterotetrameric type IIA topo, introduces
      negative supercoils into DNA by an ATP-dependent strand passage mechanism. All
      gyrase orthologs rely on a homologous set of catalytic domains for function;
      however, these enzymes also can possess species-specific auxiliary regions. The
      gyrases of many gram-negative bacteria harbor a 170-amino acid insertion of
      unknown architecture and function in the metal- and DNA-binding TOPRIM domain of
      the GyrB subunit. We have determined the structure of the 212 kDa Escherichia
      coli gyrase DNA binding and cleavage core containing this insert to 3.1 A
      resolution. We find that the insert adopts a novel, extended fold that braces the
      GyrB TOPRIM domain against the coiled-coil arms of its partner GyrA subunit.
      Structure-guided deletion of the insert greatly reduces the DNA binding,
      supercoiling and DNA-stimulated ATPase activities of gyrase. Mutation of a single
      amino acid at the contact point between the insert and GyrA more modestly impairs
      supercoiling and ATP turnover, and does not affect DNA binding. Our data indicate
      that the insert has two functions, acting as a steric buttress to pre-configure
      the primary DNA-binding site, and serving as a relay that may help coordinate
      communication between different functional domains.

PMID- 20675725
TI  - Risk factors for idiopathic orbital inflammation: a case-control study.
AB  - OBJECTIVE: To identify risk factors involved in the development of idiopathic
      orbital inflammation (IOI). METHODS: Case-control study of 69 adults who had had
      a first episode of IOI and 296 adult controls with rhegmatogenous retinal
      detachment (RD) selected from three orbital centres in The Netherlands between
      2000 and 2006. Participants filled out a questionnaire on demographic factors,
      medical history, health status and exposures for the 2&emsp14;years prior to
      disease presentation. In addition, women were questioned about previous or
      current pregnancies and their hormonal status. ORs and accompanying 95% CIs for
      IOI in relation to potential risk factors such as body mass index (BMI),
      bisphosphonates and autoimmune disease were estimated. ORs were adjusted for age,
      sex, socio-economic status, smoking and blunt orbital trauma using logistic
      regression. Analyses were carried out both with and without multiple imputation
      of missing values. RESULTS: The risk of IOI was increased in participants who had
      a higher BMI (third vs first tertile: OR, 2.88; 95% CI 1.32 to 6.32) and in
      participants who used bisphosphonates (OR 8.68; 95% CI 1.16 to 65.0). The risk
      was decreased in participants with a higher socio-economic status (third vs first
      tertile: OR 0.38; 95% CI 0.17 to 0.84) and in women who were older at first
      childbirth (third vs first tertile: OR 0.14; 95% CI 0.03 to 0.64). An almost
      significant association was found for IOI and autoimmune disease (OR 2.56; 95% CI
      0.93 to 7.05). CONCLUSIONS: IOI is associated with lower socio-economic status,
      higher BMI and use of oral bisphosphonates. In women, IOI is also associated with
      younger age at first childbirth.

PMID- 20675726
TI  - Deep anterior lamellar keratoplasty: coming of age.

PMID- 20675727
TI  - Diffuse large B cell lymphoma of the  eyelid in a patient with AIDS.

PMID- 20675728
TI  - Long-term perimetric fluctuation in patients with different stages of glaucoma.
AB  - AIM: To evaluate the long-term perimetric fluctuation (LF) in patients with
      different stages of glaucoma according to the Glaucoma Staging System 2 (GSS2).
      METHODS: This multicentre retrospective study included 161 eyes of 161 stable
      glaucoma patients undergoing four visual-field tests (Humphrey SITA-Standard
      program over the central 24 degrees  or 30 degrees ) over a 2-year period. For
      each patient, the stage of the disease was classified according to GSS2. LF was
      then calculated as the mean of the standard deviations of point-to-point
      threshold sensitivities in the four repetitions. LF in GSS2 stages was compared
      using the t test. Results LF progressively increased from stage 0 to stage 4, and
      then decreased at stage 5. Stage 4 had a peak of 3.19 +/- 0.94 dB, with
      statistically significant differences compared with all the other stages. The
      lowest LF (1.65 +/- 0.60 dB) was found for normal subjects, whereas similar data
      were found for borderline patients and those at stages 1 and 5 (2.09 +/- 0.58,
      2.13 +/- 0.57 and 2.22 +/- 0.89 dB, respectively; p > 0.13). Visual fields with
      generalised defects had a lower LF (1.90 +/- 0.81) than those with mixed (2.84 +/
      0.87, p = 0.0003) and localised (2.63 +/- 0.72, p = 0.004) defects. Conclusions
      In this study, the authors showed that the lower the visual-field defect, the
      lower was LF, except at stage 5 of GSS2. As test-retest changes exceeding LF
      could represent a sign of progression, the authors suggest that clinicians using
      this classification system calculate LF, in order to better differentiate true
      progression from variability.

PMID- 20675729
TI  - Amniotic membrane transplantation as an adjunct to medical therapy in acute
      ocular burns.
AB  - AIMS: To evaluate the role of amniotic membrane transplantation in patients with
      acute ocular burns. METHODS: In a prospective, randomised, controlled clinical
      trial, 100 patients with grade II to IV acute ocular burns (Roper Hall
      Classification) were recruited. 50 patients with grade II-III burns were graded
      as moderate burns, and 50 patients with grade IV burns were graded as severe
      burns. Both groups were individually randomised into control group (n=25) and
      study group (n=25). The corresponding grade of ocular surface burn by Dua
      classification was noted. The eyes in the study group underwent amniotic membrane
      transplantation in addition to conventional medical therapy. In the control
      group, conventional medical therapy along with mechanical release of early
      adhesions as and when necessary was instituted. Rate of healing of corneal
      epithelial defect, visual acuity, extent of corneal vascularisation, corneal
      clarity and formation of symblepharon were compared in both groups. RESULTS: In
      patients with moderate ocular burns treated with amniotic membrane
      transplantation, the rate of epithelial healing was significantly better than the
      group treated with standard medical therapy alone (p=0.0004). There was no
      overall difference in the final visual outcome, symblepharon formation, corneal
      clarity and vascularisation with or without amniotic membrane transplantation.
      CONCLUSIONS: Amniotic membrane transplantation in eyes with acute ocular burns
      promotes faster healing of epithelial defect in patients with moderate grade
      burns. There seems to be no definite long-term advantage of amniotic membrane
      transplantation over medical therapy and mechanical release of adhesions in terms
      of final visual outcome, appearance of symblepharon and corneal vascularisation
      when compared in a controlled clinical setting.

PMID- 20675730
TI  - Diagnosis of bacterial endophthalmitis by broad-range quantitative PCR.
AB  - AIM: To measure the bacterial genome in ocular fluids and to analyse the clinical
      relevance of infectious endophthalmitis. METHODS: Nineteen ocular fluid samples
      (eight aqueous humour and 11 vitreous fluid samples) were collected from 19
      patients with suspected bacterial endophthalmitis. Fifty ocular samples from
      uveitis patients were also collected along with 40 samples from patients without
      ocular inflammation and used as controls. Bacterial ribosomal DNA (16S rDNA) was
      measured by a quantitative PCR assay. RESULTS: Bacterial 16S rDNA was detected in
      patients with clinically suspected bacterial endophthalmitis (18/19, 95%). With
      the exception of one case, high copy numbers of bacterial DNA were detected
      (1.7*10(3)-1.7*10(9) copies/ml) in these patients. There were 10 samples (53%)
      with positive bacterial cultures while there were nine samples (47%) with
      positive Gram-staining. Real-time PCR detected bacterial 16S rDNA in three (6%)
      of the 50 samples from the control uveitis patients. In addition, none of the
      samples from the control patients without intraocular inflammation were positive.
      CONCLUSIONS: Quantitative broad-range PCR of bacterial 16S rDNA is a useful tool
      for diagnosing bacterial endophthalmitis.

PMID- 20675731
TI  - Novel materials to enhance corneal epithelial cell migration on keratoprosthesis.
AB  - PURPOSE: To introduce a new modification for silicone optical core
      Keratoprosthesis. METHODS: Using mixtures of 2-hydroxyethyl methacrylate and
      acrylic acid polydimethylsiloxane (PDMS) films were modified with two-step oxygen
      plasma treatment, and then type I collagen was immobilised onto this modified
      surfaces. Both the biocompatibility of the modified films and cell behaviour on
      the surface of these films were investigated by in vitro tests, and formation of
      epithelial cell layer was evaluated by implantation of the modified films in the
      corneas of 10 rabbits. RESULTS: In vitro studies indicated that the number of
      attached and proliferated cells onto modified PDMS in comparison with the
      unmodified PDMS significantly increased. Histological studies showed that corneal
      epithelial cells migrated on the anterior surface of the modified films after
      1week. The corneal epithelial cell formed an incomplete monolayer cellular sheet
      after 10days. A complete epithelialisation on the modified surface was formed
      after 21days. The epithelial layer persisted on the anterior surface of implant
      after 1-month and 3-month follow-up. CONCLUSION: This method may have potential
      use in silicone optical core Keratoprosthesis.

PMID- 20675732
TI  - Retinal optical coherence tomography: past, present and future perspectives.
AB  - Optical coherence tomography (OCT) has undergone substantial changes since its
      first use in the 1990s. Although the first generation of OCT systems heralded a
      new era in the non-invasive diagnostic options in ophthalmology, they did not
      reveal much detail. Later devices offered more information and helped in the
      diagnosis and treatment of a variety of pathological conditions, primarily of the
      retina. With today's spectral-domain type models ophthalmologists are offered a
      comprehensive tool with the opportunity for early diagnosis and precise
      monitoring of patients with retinal and glaucomatous pathologies. However, as
      experience with these new devices grows and demands by clinicians and researchers
      rise, further improvements need to be addressed. Future developments in the
      improvement of the transverse resolution and extension of the penetration depth
      are to be expected. New modalities such as polarisation sensitive OCT (PS-OCT) or
      Doppler OCT are now in use and promise additional insights in the properties of
      physiological and pathological tissue. While PS-OCT reveals further detail in
      alterations of the retinal pigment epithelium, Doppler OCT gives additional
      information about blood flow measurements. With these and further new
      developments, OCT will continue to be an invaluable instrument in the
      armamentarium of modern ophthalmology.

PMID- 20675733
TI  - Never too old to harbour a young man's disease?

PMID- 20675734
TI  - Finding the will to recover: philosophical perspectives on agency and the sick
      role.
AB  - Recovery from a range of common medical conditions requires patients to have the
      will to change their behaviour. The authors argue that the proper recognition of
      the role of willpower in recovery is necessary for effective treatment.

PMID- 20675735
TI  - Ethics Committee or Community? Examining the identity of Czech Ethics Committees
      in the period of transition.
AB  - Reflecting on a three year long exploratory research of ethics committees in the
      Czech Republic authors discuss the current role and identity of research ethics
      committees. The research of Czech ethics committees focused on both self
      presentation and self-understanding of ECs members, and how other stakeholders
      (representatives of the pharmaceutical industry) view them. The exploratory
      research was based on formal and informal communication with the members of the
      ethics committees. Members of the research team took part at six regular
      voluntary meetings of the ethics committees' members, organised by the Forum of
      Czech Ethics Committees, and at three summer schools of medical ethics. There
      were realised twenty-five semi-structured interviews as well as six focus group
      sessions and a participant observation of several regular meetings of three
      ethics committees. On the grounds of experience from the interviews a simple
      questionnaire survey was realised among the members of the ethics committees. The
      ethics committees comprise a community of members working voluntarily, without
      claims to remuneration or prestige; the unifying goal is protection of subjects
      of research. The principal working methods are dialogue and agreement. The
      members of the ethics committees thus, among other things, create an informal
      community, which can be to a certain extent seen as a Kantian ethical community
      in a weak sense. The phenomenon of ethics committees can also be described by
      terms of an epistemic community and a community of practice. These concepts,
      which are borrowed from other authors and areas, are used as a way how to think
      of ECs role and identity a bit differently and are meant as a contribution to the
      current international debate on the topic.

PMID- 20675736
TI  - Ethical issues surrounding do not attempt resuscitation orders: decisions,
      discussions and deleterious effects.
AB  - Since their introduction as 'no code' in the 1980s and their later formalization
      to 'do not resuscitate' orders, such directions to withhold potentially life
      extending treatments have been accompanied by multiple ethical issues. The
      arguments for when and why to instigate such orders are explored, including a
      consideration of the concept of futility, allocation of healthcare resources, and
      reaching a balance between quality of life and quality of death. The merits and
      perils of discussing such decisions with patients and/or their relatives are
      reviewed and the unintended implications of 'do not attempt resuscitation' orders
      are examined. Finally, the paper explores some alternative methods to approaching
      the resuscitation decision, and calls for empirical evaluation of such methods
      that may reduce the ethical dilemmas physicians currently face.

PMID- 20675737
TI  - Eyewitness in Erewhon academic hospital. Part 12: the fall of the house of
      ethics.

PMID- 20675738
TI  - Complex calculations: ethical issues in involving at-risk healthy individuals in
      dementia research.
AB  - In dementia research evidence is mounting that therapeutic strategies that target
      moderate and even mild Alzheimer's disease may be missing the 'therapeutic
      window'. Given that the neuropathology that leads to Alzheimer's disease probably
      begins somewhere between 10 and 15 years before symptoms manifest, many believe
      that the optimal therapeutic strategy would target persons in the earliest phases
      of disease development or even earlier. This would include, for example, persons
      with prodromal Alzheimer's and even persons who are deemed at risk. Given the
      nature of research involving the central nervous system, it is conceivable that
      some therapeutic investigations may involve an increase over minimal risk. This
      paper examines how, in dementia research, at-risk persons, although healthy,
      bring multiple and intersecting vulnerabilities to the prospect of research
      participation even though they are clinically healthy. Current guidelines for
      research ethics may not provide adequately for the nuances of 'healthy
      individuals' and their possible vulnerabilities. In the context of
      neurodegenerative disease, the fact of being 'at risk' alters the vulnerability
      profile in significant ways. While healthy persons who are at risk of developing
      dementia may not appear to warrant placement in the research category of
      vulnerable participants (alongside prisoners, pregnant women and children)
      careful regard for the vulnerabilities that arise as a result of the intersecting
      circumstances of being healthy and at risk of an incurable disease are worthy of
      increased attention and consideration, particularly as the research effort for
      the increasingly prevalent disease of Alzheimer's moves forward.

PMID- 20675739
TI  - Asperger syndrome and the supposed obligation not to bring disabled lives into
      the world.
AB  - Asperger syndrome (AS) is an autistic spectrum condition that shares the range of
      social impairments associated with classic autism widely regarded as disabling,
      while also often giving rise to high levels of ability in areas such as maths,
      science, engineering and music. The nature of this striking duality of disability
      and ability is examined, along with its implications for our thinking about
      disability and the relevance of levels and kinds of disability to reproductive
      choices. In particular, it may be seen as posing a challenge to John Harris's
      influential position in reproductive ethics relating to disability. The paper
      argues that if, as Harris maintains, there is a quite general moral obligation to
      avoid bringing disabled lives into the world regardless of the level of
      disability, then AS must be seen as having a strong claim to be exempt from such
      an obligation. However, a broader critique of Harris's position leads to the
      conclusion that, in fact, this putative obligation does not exist.

PMID- 20675740
TI  - Ancillary care duties: the demands of justice.
AB  - Ancillary care is care that research participants need that is not essential to
      make the research safe or scientifically valid and is not needed to remedy
      injuries that eventuate as a result of the research project itself. Ancillary
      care duties have recently been defended on the grounds of beneficence,
      entrustment, utility and consent. Justice has also been mentioned as a possible
      basis of ancillary care duties, but little attention has been paid to this
      approach. In this paper, the author seeks to rectify this omission by arguing
      that ancillary care duties can be based on a principle of justice as
      rectification.

PMID- 20675742
TI  - Multiple regulatory mechanisms act in concert to control ferroportin expression
      and heme iron recycling by macrophages.

PMID- 20675743
TI  - Inherited bone marrow failure syndromes.

PMID- 20675744
TI  - Front-line treatment of mantle cell lymphoma.

PMID- 20675745
TI  - The measurement of patellar height: a review of the methods of imaging.
AB  - Many radiographic techniques have been described for measuring patellar height.
      They can be divided into two groups: those that relate the position of the
      patella to the femur (direct) and those that relate it to the tibia (indirect).
      This article looks at the methods that have been described, the logic behind
      their conception and the critical analyses that have been performed to test them.

PMID- 20675746
TI  - The surgical management of metastatic epidural compression of the spinal cord.
AB  - Metastatic epidural compression of the spinal cord is a significant source of
      morbidity in patients with systemic cancer. With improved oncological treatment,
      survival in these patients is improving and metastatic cord compression is
      encountered increasingly often. The treatment is mostly palliative. Surgical
      management involves early circumferential decompression of the cord with
      concomitant stabilisation of the spine. Patients with radiosensitive tumours
      without cord compression benefit from radiotherapy. Spinal stereotactic
      radiosurgery and minimally invasive techniques, such as vertebroplasty and
      kyphoplasty, with or without radiofrequency ablation, are promising options for
      treatment and are beginning to be used in selected patients with spinal
      metastases. In this paper we review the surgical management of patients with
      metastatic epidural spinal cord compression.

PMID- 20675747
TI  - The biomechanics of pedicle screw-based instrumentation.
AB  - There are three basic concepts that are important to the biomechanics of pedicle
      screw-based instrumentation. First, the outer diameter of the screw determines
      pullout strength, while the inner diameter determines fatigue strength. Secondly,
      when inserting a pedicle screw, the dorsal cortex of the spine should not be
      violated and the screws on each side should converge and be of good length.
      Thirdly, fixation can be augmented in cases of severe osteoporosis or revision. A
      trajectory parallel or caudal to the superior endplate can minimise breakage of
      the screw from repeated axial loading. Straight insertion of the pedicle screw in
      the mid-sagittal plane provides the strongest stability. Rotational stability can
      be improved by adding transverse connectors. The indications for their use
      include anterior column instability, and the correction of rotational deformity.

PMID- 20675748
TI  - Total hip replacement in morbidly obese patients with osteoarthritis: results of
      a prospectively matched study.
AB  - We compared 55 consecutive total hip replacements performed on 53 morbidly obese
      patients with osteoarthritis with a matched group of 55 total hip replacements in
      53 non-obese patients. The groups were matched for age, gender, prosthesis type,
      laterality and preoperative Harris Hip Score. They were followed prospectively
      for five years and the outcomes were assessed using the Harris Hip Score, the
      Short-form 36 score and radiological findings. Survival at five years using
      revision surgery as an endpoint, was 90.9% (95% confidence interval 82.9 to 98.9)
      for the morbidly obese and 100% for the non-obese patients. The Harris Hip and
      the Short-form 36 scores were significantly better in the non-obese group (p <
      0.001). The morbidly obese patients had a higher rate of complications (22% vs
      5%, p = 0.012), which included dislocation and both superficial and deep
      infection. In light of these inferior results, morbidly obese patients should be
      advised to lose weight before undergoing a total hip replacement, and counselled
      regarding the complications. Despite these poorer results, however, the patients
      have improved function and quality of life.

PMID- 20675749
TI  - Optimal acetabular orientation for hip resurfacing.
AB  - Pseudotumours are a rare complication of hip resurfacing. They are thought to be
      a response to metal debris which may be caused by edge loading due to poor
      orientation of the acetabular component. Our aim was to determine the optimal
      acetabular orientation to minimise the risk of pseudotumour formation. We matched
      31 hip resurfacings revised for pseudotumour formation with 58 controls who had a
      satisfactory outcome from this procedure. The radiographic inclination and
      anteversion angles of the acetabular component were measured on anteroposterior
      radiographs of the pelvis using Einzel-Bild-Roentgen-Analyse software. The mean
      inclination angle (47 degrees, 10 degrees to 81 degrees) and anteversion angle
      (14 degrees, 4 degrees to 34 degrees) of the pseudotumour cases were the same (p
      = 0.8, p = 0.2) as the controls, 46 degrees (29 degrees to 60 degrees) and 16
      degrees (4 degrees to 30 degrees) respectively, but the variation was greater.
      Assuming an accuracy of implantation of +/- 10 degrees about a target position,
      the optimal radiographic position was found to be approximately 45 degrees of
      inclination and 20 degrees of anteversion. The incidence of pseudotumours inside
      the zone was four times lower (p = 0.007) than outside the zone. In order to
      minimise the risk of pseudotumour formation we recommend that surgeons implant
      the acetabular component at an inclination of 45 degrees (+/- 10) and anteversion
      of 20 degrees (+/- 10) on post-operative radiographs. Because of differences
      between the radiographic and the operative angles, this may be best achieved by
      aiming for an inclination of 40 degrees and an anteversion of 25 degrees.

PMID- 20675750
TI  - Uncemented custom computer-assisted design and manufacture of hydroxyapatite
      coated femoral components: survival at 10 to 17 years.
AB  - We present the 10- to 17-year results of 112 computer-assisted design computer
      assisted manufacture femoral components. The total hip replacements were
      performed between 1992 and 1998 in 111 patients, comprising 53 men and 58 women.
      Their mean age was 46.2 years (24.6 to 62.2) with a mean follow-up of 13 years
      (10 to 17). The mean Harris Hip Score improved from 42.4 (7 to 99) to 90.3 (38 to
      100), the mean Oxford Hip Score from 43.1 (12 to 59) to 18.2 (12 to 51) and the
      mean Western Ontario MacMasters University Osteoarthritis Index score from 57.0
      (7 to 96) to 11.9 (0 to 85). There was one revision due to failure of the
      acetabular component but no failures of the femoral component. There were no
      revisions for aseptic loosening. The worst-case survival in this cohort of custom
      femoral components at 13.2 years follow-up was 98.2% (95% confidence interval 95
      to 99). Overall survival of this series of total hip replacements was 97.3% (95%
      confidence interval 95 to 99). These results are comparable with the best medium-
      to long-term results for femoral components used in primary total hip replacement
      with any means of fixation.

PMID- 20675751
TI  - Total knee replacement in patients with end-stage haemophilic arthropathy: 25
      year results.
AB  - Haemophilia is an x-linked inherited bleeding disorder which can cause severe
      arthropathy. We have reviewed the results of 70 primary total knee replacements
      (TKR) performed in 57 haemophilic patients between 1983 and 2007. The functional
      results were assessed using the Hospital for Special Surgery (HSS) knee scoring
      system and Kaplan-Meier survivorship analysis. Six patients died. HSS scores were
      available for 60 TKRs at a mean follow-up of 9.2 years (2 to 23); 57 (95%) had
      good or excellent results. Deep infection was recorded in one patient. Kaplan
      Meier analysis using infection and aseptic loosening as endpoints showed the
      survival rate at 20 years to be 94.0%. A reduction in infection, spontaneous
      haemarthrosis and improvement in the quality of life were noted to justify
      surgery in our series of patients with a mean age of 43 (25 to 70). We have found
      that using the latest techniques of continuous infusion of clotting Factor have
      significantly helped to reduce the complication rates and have achieved results
      which match those of the non-haemophilic population undergoing TKR.

PMID- 20675753
TI  - The long-term functional and radiological outcome after open reconstruction of
      the anterior cruciate ligament.
AB  - We identified a series of 128 patients who had unilateral open reconstruction of
      the anterior cruciate ligament (ACL) by a single surgeon between 1993 and 2000.
      In all, 79 patients were reviewed clinically and radiologically eight to 15 years
      after surgery. Assessment included measurement of the Lysholm and Tegner scores,
      the ACL quality-of-life score and the Short Form-12 score, as well as the
      International Knee Documentation Committee clinical assessment, measurement of
      laxity by the KT-1000 arthrometer, a single-leg hop test and standardised
      radiography of both knees using the uninjured knee as a control. Of the injured
      knees, 46 (57%) had definite radiological evidence of osteoarthritis (Kellgren
      Lawrence grade 2 or 3), with a mean difference between the injured and non
      injured knees of 1.2 grades. The median ACL quality-of-life score was 80
      (interquartile range (IQR) 60 to 90), the Lysholm score 84 (IQR 74 to 95), the
      Short Form-12 physical component score 54 (IQR 49 to 56) and the mean Hop Index
      0.94 (0.52 to 1.52). In total 58 patients were graded as normal, 20 as nearly
      normal and one as abnormal on the KT-1000 assessment and pivot-shift testing.
      Taking the worst-case scenario of assuming all non-attenders (n = 48), two septic
      failures and one identified unstable knee found at review to be failures, the
      failure rate was 40%. Only two of the patients reviewed stated that they would
      not have similar surgery again. Open reconstruction of the ACL gives good,
      durable functional results, but with a high rate of radiologically evident
      osteoarthritis.

PMID- 20675752
TI  - The effect of anteroposterior laxity on the range of movement and knee function
      following a cruciate-retaining total knee replacement.
AB  - The amount of anteroposterior laxity required for a good range of movement and
      knee function in a cruciate-retaining total knee replacement (TKR) continues to
      be debated. We undertook a retrospective study to evaluate the effects of
      anteroposterior laxity on the range of movement and knee function in 55 patients
      following the e-motion cruciate-retaining TKR with a minimum follow-up of two
      years. The knees were divided into stable (anteroposterior translation, < or = 10
      mm, 38 patients) and unstable (anteroposterior translation, > 10 mm, 17) groups
      based on the anteroposterior laxity, measured using stress radiographs. We
      compared the Hospital for Special Surgery (HSS) scores, the Western Ontario
      MacMasters University Osteoarthritis (WOMAC) index, weight-bearing flexion, non
      weight-bearing flexion and the reduction of flexion under weight-bearing versus
      non-weight-bearing conditions, which we referred to as delta flexion, between the
      two groups at the final follow-up. There were no differences between the stable
      and unstable groups with regard to the mean HHS and WOMAC total scores, as well
      as weight-bearing and non-weight-bearing flexion (p = 0.277, p = 0.082, p = 0.095
      and p = 0.646, respectively). However, the stable group had a better WOMAC
      function score and less delta flexion than the unstable group (p = 0.011 and p =
      0.005, respectively). Our results suggest that stable knees with laxity < or = 10
      mm have a good functional outcome and less reduction of flexion under weight
      bearing conditions than unstable knees with laxity > 10 mm following an e-motion
      cruciate-retaining TKR.

PMID- 20675754
TI  - Capsuloligamentotaxis and definitive fixation by an ankle-spanning Ilizarov
      fixator in high-energy pilon fractures.
AB  - Open reduction and internal fixation of high-energy pilon fractures are often
      associated with serious complications. Various methods have been used to treat
      these injuries, with variable results. A total of 17 consecutive patients with
      pilon fractures of AO/OTA type 43-B3 (n = 1), type C2 (n = 12) and type C3 (n =
      4) were treated by indirect reduction by capsuloligamentotaxis and stabilisation
      using an ankle-spanning Ilizarov fixator. The calcaneal ring was removed at a
      mean of 3.7 weeks (3 to 6). A total of 16 patients were available for follow-up
      at a mean of 29 months (23 to 43). The mean time to healing was 15.8 weeks (13 to
      23). Nine patients had pin-track infections but none had deep infection or
      osteomyelitis. Four patients (25%) had malunion. Fair, good or excellent ankle
      scores were found in 14 patients. External fixation with a ring fixator achieves
      stable reduction of the fractured fragments without additional trauma to soft
      tissues. With minimum complications and good healing results, the Ilizarov
      apparatus is particularly useful for high-energy pilon fractures.

PMID- 20675755
TI  - The use of patient-reported outcome measures and patient satisfaction ratings to
      assess outcome in hemiarthroplasty of the shoulder.
AB  - We have compared the outcome of hemiarthroplasty of the shoulder in three
      distinct diagnostic groups, using survival analysis as used by the United Kingdom
      national joint registers, patient-reported outcome measures (PROMs) as
      recommended by Darzi in the 2008 NHS review, and transition and satisfaction
      questions. A total of 72 hemiarthroplasties, 19 for primary osteoarthritis (OA)
      with an intact rotator cuff, 22 for OA with a torn rotator cuff, and 31 for
      rheumatoid arthritis (RA), were followed up for between three and eight years.
      All the patients survived, with no revisions or dislocations and no significant
      radiological evidence of loosening. The mean new Oxford shoulder score
      (minimum/worst 0, maximum/best 48) improved significantly for all groups (p <
      0.001), in the OA group with an intact rotator cuff from 21.4 to 38.8 (effect
      size 2.9), in the OA group with a torn rotator cuff from 13.3 to 27.2 (effect
      size 2.1) and in the RA group from 13.7 to 28.0 (effect size 3.1). By this
      assessment, and for the survival analysis, there was no significant difference
      between the groups. However, when ratings using the patient satisfaction
      questions were analysed, eight (29.6%) of the RA group were 'disappointed',
      compared with one (9.1%) of the OA group with cuff intact and one (7.7%) of the
      OA group with cuff torn. All patients in the OA group with cuff torn indicated
      that they would undergo the operation again, compared to ten (90.9%) in the OA
      group with cuff intact and 20 (76.9%) in the RA group. The use of revision rates
      alone does not fully represent outcome after hemiarthroplasty of the shoulder.
      Data from PROMs provides more information about change in pain and the ability to
      undertake activities and perform tasks. The additional use of satisfaction
      ratings shows that both the rates of revision surgery and PROMs need careful
      interpretation in the context of patient expectations.

PMID- 20675756
TI  - Does diabetes affect outcome after arthroscopic repair of the rotator cuff?
AB  - We compared the outcome of arthroscopic repair of the rotator cuff in 32 diabetic
      patients with the outcome in 32 non-diabetic patients matched for age, gender,
      size of tear and comorbidities. The Constant-Murley score improved from a mean of
      49.2 (24 to 80) pre-operatively to 60.8 (34 to 95) post-operatively (p = 0.0006)
      in the diabetic patients, and from 46.4 (23 to 90) pre-operatively to 65.2 (25 to
      100) post-operatively (p = 0.0003) in the non-diabetic patients at six months.
      This was significantly greater (p = 0.0002) in non-diabetic patients (18.8) than
      in diabetics (11.6). There was no significant change in the mean mental component
      of the Short-Form 12, but the mean physical component increased from 35 to 41 in
      non-diabetics (p = 0.0001), and from 37 to 39 (p = 0.15) in diabetics. These
      trends were observed at one year. Patients with diabetes showed improvement of
      pain and function following arthroscopic rotator cuff repair in the short term,
      but less than their non-diabetic counterparts.

PMID- 20675757
TI  - Polymorphism in interleukin-6 gene is associated with bone mineral density in
      patients with adolescent idiopathic scoliosis.
AB  - Low bone mass and osteopenia have been described in the axial and peripheral
      skeleton of patients with adolescent idiopathic scoliosis (AIS). Recently, many
      studies have shown that gene polymorphism is related to osteoporosis. However, no
      studies have linked the association between IL6 gene polymorphism and bone mass
      in AIS. This study examined the association between bone mass and IL6 gene
      polymorphism in 198 girls with AIS. The polymorphisms of IL6-597 G-->A, IL6-572 G
      ->C and IL6-174 G-->A and the bone mineral density in the lumbar spine and
      femoral neck were analysed and compared with their levels in healthy controls.
      The mean bone mineral density at both sites in patients with AIS was decreased
      compared with controls (p = 0.0022 and p = 0.0013, respectively). Comparison of
      genotype frequencies between AIS and healthy controls revealed a statistically
      significant difference in IL6-572 G-->C polymorphism (p = 0.0305). There was a
      significant association between the IL6-572 G-->C polymorphism and bone mineral
      density in the lumbar spine, with the CC genotype significantly higher with the
      GC (p = 0.0124) or GG (p = 0.0066) genotypes. These results suggest that the IL6
      572 G-->C polymorphism is associated with bone mineral density in the lumbar
      spine in Korean girls with AIS.

PMID- 20675758
TI  - Spondylolysis originates in the ventral aspect of the pars interarticularis: a
      clinical and biomechanical study.
AB  - Lumbar spondylolysis is a stress fracture of the pars interarticularis. We have
      evaluated the site of origin of the fracture clinically and biomechanically. Ten
      adolescents with incomplete stress fractures of the pars (four bilateral) were
      included in our study. There were seven boys and three girls aged between 11 and
      17 years. The site of the fracture was confirmed by axial and sagittal
      reconstructed CT. The maximum principal tensile stresses and their locations in
      the L5 pars during lumbar movement were calculated using a three-dimensional
      finite-element model of the L3-S1 segment. In all ten patients the fracture line
      was seen only at the caudal-ventral aspect of the pars and did not spread
      completely to the craniodorsal aspect. According to the finite-element analysis,
      the higher stresses were found at the caudal-ventral aspect in all loading modes.
      In extension, the stress was twofold higher in the ventral than in the dorsal
      aspect. Our radiological and biomechanical results were in agreement with our
      clinical observations.

PMID- 20675759
TI  - Factors affecting the incidence of infection in hip and knee replacement: an
      analysis of 5277 cases.
AB  - Infection remains a significant and common complication after joint replacement
      and there is debate about which contributing factors are important. Few studies
      have investigated the effect of the operating time on infection. We collected
      data prospectively from 5277 hip and knee replacements which included the type of
      procedure, the operating time, the use of drains, the operating theatre, surgeon,
      age and gender. In a subgroup of 3449 knee replacements further analysis was
      carried out using the tourniquet time in place of the operating time. These
      variables were assessed by the use of generalised linear modelling against
      superficial, deep or joint-space post-operative infection as defined by the
      Australian Surgical-Site Infection criteria. The overall infection rate was
      0.98%. In the replacement data set both male gender (z = 3.097, p = 0.00195) and
      prolonged operating time (z = 4.325, p < 0.001) were predictive of infection. In
      the knee subgroup male gender (z = 2.250, p = 0.02447), a longer tourniquet time
      (z = 2.867, p = 0.00414) and total knee replacement (versus unicompartmental knee
      replacement) (z = -2.052, p = 0.0420) were predictive of infection. These
      findings support the view that a prolonged operating time and male gender are
      associated with an increased incidence of infection. Steps to minimise intra
      operative delay should be instigated, and care should be exercised when
      introducing measures which prolong the duration of joint replacement.

PMID- 20675760
TI  - Custom-made endoprostheses for the femoral amputation stump: an alternative to
      hip disarticulation in tumour surgery.
AB  - Disarticulation of the hip in patients with high-grade tumours in the upper thigh
      results in significant morbidity. In patients with no disease of the proximal
      soft tissue a femoral stump may be preserved, leaving a fulcrum for movement and
      weight-bearing. We reviewed nine patients in whom the oncological decision would
      normally be to disarticulate, but who were treated by implantation of an
      endoprosthesis in order to create a functioning femoral stump. The surgery was
      undertaken for chondrosarcoma in four patients, pleomorphic sarcoma in three,
      osteosarcoma in one and fibrous dysplasia in one. At follow-up at a mean of 80
      months (34 to 132), seven patients were alive and free from disease, one had died
      from lung metastases and another from a myocardial infarction. The mean
      functional outcome assessment was 50 (musculoskeletal tumor society), 50 and 60
      (physical and mental Short-form 36 scores). Implantation of an endoprosthesis
      into the stump in carefully selected patients allows fitting of an above-knee
      prosthesis and improves wellbeing and the functional outcome.

PMID- 20675761
TI  - Chronic haematogenous osteomyelitis in children: a retrospective review of 167
      patients in Malawi.
AB  - We present a retrospective review of 167 patients aged 18 years and under who
      were treated for chronic haematogenous osteomyelitis at our elective orthopaedic
      hospital in Malawi over a period of four years. The median age at presentation
      was eight years (1 to 18). There were 239 hospital admissions for treatment
      during the period of the study. In 117 patients one admission was necessary, in
      35 two, and in 15 more than two. A surgical strategy of infection control
      followed by reconstruction and stabilisation was employed, based on the Beit CURE
      radiological classification of chronic haematogenous osteomyelitis as a guide to
      treatment. At a minimum follow-up of one year after the end of the study none of
      the patients had returned to our hospital with recurrent infection. A total of
      350 operations were performed on the 167 patients. This represented 6.7% of all
      children's operations performed in our hospital during this period. One operation
      only was required in 110 patients and none required more than three. Below-knee
      amputation was performed in two patients with chronic calcaneal osteomyelitis as
      the best surgical option for function. The most common organism cultured from
      operative specimens was Staphylococcus aureus, and the tibia was the bone most
      commonly affected. Polyostotic osteomyelitis occurred in four patients. We
      believe this is the largest reported series of patients treated for chronic
      haematogenous osteomyelitis.

PMID- 20675762
TI  - The normal centre-edge angle of Wiberg in the Chinese population: a population
      based cross-sectional study.
AB  - This study was designed to provide normal reference values for the centre-edge
      angle of Wiberg in the Chinese population by measuring 1494 radiographs according
      to the criteria of Tonnis. The mean angle was 23.1 degrees (4.7 degrees to 46.4
      degrees) in childhood (four to nine years), increasing to 28.9 degrees (6 degrees
      to 48 degrees) in adolescence (10 to 18 years) and reaching 32.8 degrees (13.7
      degrees to 58.8 degrees) in adults. The angle was positively correlated with age,
      increasing by a mean of 0.78 degrees annually before adulthood and by 0.070
      degrees annually in adults. A relative upward tendency after middle age might
      contribute to degenerative changes. No gender difference was discovered. The
      change in the angle with age was similar to that observed in other ethnic groups,
      showing moderate differences in the average of individual age groups, but the
      ethnic differences are not sufficient to explain the variation of incidence of
      developmental dysplasia of the hip in different races.

PMID- 20675763
TI  - Displaced fracture of the femoral neck in children: open versus closed reduction.
AB  - We have investigated whether early anatomical open reduction and internal
      fixation (ORIF) reduces the incidence of complications of fracture of the femoral
      neck in children, including avascular necrosis, compared with closed reduction
      and internal fixation (CRIF). We retrospectively reviewed 27 such fractures (15
      type-II and 12 type-III displaced fractures) in children younger than 16 years of
      age seen in our hospital between February 1989 and March 2007. We divided the
      patients into three groups according to the quality of the reduction (anatomical,
      acceptable, and unacceptable) and the clinical results into two groups
      (satisfactory and unsatisfactory). Of the 15 fractures treated by ORIF, 14
      (93.3%) had anatomical reduction and reduction was acceptable in one. Of the 12
      treated by CRIF, three (25.0%) had anatomical reduction, eight had acceptable
      reduction (66.7%), and one (8.3%) unacceptable reduction. Of the 15 fractures
      treated by ORIF, 14 (93.3%) had a good result and one a fair result. Of the 12
      treated by CRIF, seven (58.3%) had a good result, two (16.7%) a fair result and
      three (25.0%) a poor result. There were seven complications in five patients.
      ORIF gives better reduction with fewer complications, including avascular
      necrosis, than does CRIF in fractures of the femoral neck in children.

PMID- 20675764
TI  - The effect of injections of botulinum toxin type A combined with casting on the
      equinus gait of children with cerebral palsy.
AB  - Our aim was to evaluate the effect of adding inhibitory casting to the treatment
      of young children with cerebral palsy who received injections of botulinum
      neurotoxin A (BoNT-A) to gastrocnemius for equinus gait. Of the 20 patients in
      the series, 11 in group A had inhibitory casts applied on the day of the first
      set of BoNT-A injections and nine in group B did not have casting. Both groups
      received another BoNT-A injection four months later. The patients were followed
      for eight months and examined at five intervals. Both groups showed significant
      improvement in gait parameters and function (p < 0.0001) and selective motor
      control (p = 0.041, - 0.036) throughout the study. Group A had significantly
      better passive dorsiflexion of the ankle (p = 0.029), observational gait score (p
      = 0.006) and selective motor control (p = 0.036). We conclude that the addition
      of inhibitory casting enhances and prolongs the results of treatment and mainly
      influences the passive range of movement, while BoNT-A mostly influences the
      dynamic motion. The second injection further improved the results of most
      parameters. The gross motor function measure, the selective motor control test
      and the modified Tardieu scale correlated well with the results of treatment. We
      recommend the use of inhibitory casting whenever augmentation of the effect of
      treatment with BoNT-A is needed.

PMID- 20675765
TI  - Repair of a post-traumatic cartilage defect with a cell-free polymer-based
      cartilage implant: a follow-up at two years by MRI and histological review.
AB  - Microfracture is frequently used as the first line of treatment for the repair of
      traumatic cartilage defects. We present the clinical and histological results 18
      months to two-years after treatment in a 26-year-old male with a post-traumatic
      chondral defect of the medial femoral condyle managed by microfracture covered
      with chondrotissue, a cell-free cartilage implant made of a resorbable
      polyglycolic acid felt and hyaluronic acid.

PMID- 20675766
TI  - A new barbed device for repair of flexor tendons.
AB  - We split 100 porcine flexor tendons into five groups of 20 tendons for repair.
      Three groups were repaired using the Pennington modified Kessler technique, the
      cruciate or the Savage technique, one using one new device per tendon and the
      other with two new devices per tendon. Half of the tendons received supplemental
      circumferential Silfverskiold type B cross-stitch. The repairs were loaded to
      failure and a record made of their bulk, the force required to produce a 3 mm
      gap, the maximum force applied before failure and the stiffness. When only one
      device was used repairs were equivalent to the Pennington modified Kessler for
      all parameters except the force to produce a 3 mm gap when supplemented with a
      circumferential repair, which was equivalent to the cruciate. When two devices
      were used the repair strength was equivalent to the cruciate repair, and when the
      two-device repair was supplemented with a circumferential suture the force to
      produce a 3 mm gap was equivalent to that of the Savage six-strand technique.

PMID- 20675767
TI  - Effect of laceration and trimming of a tendon on the coefficient of friction
      along the A2 pulley: an in vitro study on turkey tendon.
AB  - We carried out lacerations of 50%, followed by trimming, in ten turkey flexor
      tendons in vitro and measured the coefficient of friction at the tendon-pulley
      interface with loads of 200 g and 400 g and in 10 degrees , 30 degrees, 50
      degrees and 70 degrees of flexion. Laceration increased the coefficient of
      friction from 0.12 for the intact tendon to 0.3 at both the test loads. Trimming
      the laceration reduced the coefficient of friction to 0.2. An exponential
      increase in the gliding resistance was found at 50 degrees and 70 degrees of
      flexion (p = 0.02 and p = 0.003, respectively) following trimming compared to
      that of the intact tendon. We concluded that trimming partially lacerated flexor
      tendons will reduce the gliding resistance at the tendon-pulley interface, but
      will lead to fragmentation and triggering of the tendon at higher degrees of
      flexion and loading. We recommend that higher degrees of flexion be avoided
      during early post-operative rehabilitation following trimming of a flexor tendon.

PMID- 20675768
TI  - Mapping the strain distribution on the proximal femur with titanium and flexible
      stemmed implants using digital image correlation.
AB  - We implanted titanium and carbon fibre-reinforced plastic (CFRP) femoral
      prostheses of the same dimensions into five prosthetic femora. An abductor jig
      was attached and a 1 kN load applied. This was repeated with five control femora.
      Digital image correlation was used to give a detailed two-dimensional strain map
      of the medial cortex of the proximal femur. Both implants caused stress shielding
      around the calcar. Distally, the titanium implant showed stress shielding,
      whereas the CFRP prosthesis did not produce a strain pattern which was
      statistically different from the controls. There was a reduction in strain beyond
      the tip of both the implants. This investigation indicates that use of the CFRP
      stem should avoid stress shielding in total hip replacement.

PMID- 20675769
TI  - The biggest debate since the NHS was founded.

PMID- 20675770
TI  - Shifting the deckchairs on the NHS Titanic.

PMID- 20675771
TI  - Homelessness is a healthcare issue.

PMID- 20675772
TI  - NHS after the May 2010 elections.

PMID- 20675773
TI  - Thomas Nettleton and the dawn of quantitative assessments of the effects of
      medical interventions.

PMID- 20675774
TI  - Swine flu: is panic the key to successful modern health policy?

PMID- 20675775
TI  - Paediatric respiratory disease: past, present and future.

PMID- 20675776
TI  - European Respiratory Society MD PhD programme in respiratory science.

PMID- 20675777
TI  - When asthma diagnosis becomes a challenge.

PMID- 20675778
TI  - Superoxide dismutase: master and commander?

PMID- 20675779
TI  - Strength and weakness of the new TNM classification for lung cancer.

PMID- 20675780
TI  - Recovery of body composition improves long-term outcomes after lung volume
      reduction surgery for emphysema.
AB  - Nutritional status deteriorates along with progression of emphysema, with the
      decline of body composition correlating with risk of disease-related events. Lung
      volume reduction surgery (LVRS), by improving respiratory function and recovering
      body composition, may influence long-term disease-related morbidity and mortality
      when compared to respiratory rehabilitation (RR). In this non-randomised study,
      44 male patients with moderate-to-severe emphysema underwent LVRS, while 35
      received RR. Respiratory parameters, body composition, number and time-to
      occurrence of disease-related events were evaluated for 5 yrs. After LVRS,
      respiratory and nutritional parameters had significantly greater and longer
      lasting improvements than after RR. Disease-related events occurred later and
      less frequently after surgery than after rehabilitation, with better morbidity
      and mortality survival curves (p<0.01 and p<0.03, respectively). Body mass index
      (BMI) > or =23kg x m(-2), BODE (BMI, airflow obstruction, dyspnoea, exercise
      capacity) index < or =2 and fat-free mass index (FFMI) > or =16kg x m(-2) at 1 yr
      were the best positive predictors of post-operative outcomes (p<0.03, p<0.04 and
      p<0.005, respectively). Reduction in residual volume at 36 months after surgery
      was significantly correlated with the increase of BMI (rho = -0.56, p = 0.009)
      and FFMI (rho = -0.64, p = 0.001). LVRS significantly and durably improved
      respiratory function and body composition over RR. Relationships among residual
      volume, BMI, FFMI and disease-related events suggest that recovery in respiratory
      dynamics improves nutritional status, thus significantly reducing long-term
      disease-related morbidity and mortality.

PMID- 20675781
TI  - Childhood asthma and infection: virus-induced exacerbations as determinants and
      modifiers.
AB  - Respiratory infections have been implicated in the origin and exacerbation of
      asthma in a variety of ways; however, systemisation of this knowledge in a way
      helpful for disease management remains suboptimal. Several conceptual issues need
      to be taken into account: the fact that the effects of an infection may vary
      according to genetic background, the current immune status of the host, and
      parallel environmental stimuli, in addition to the particular infectious agent
      itself. Moreover, childhood is a very special period because of the continuous
      processes taking place, such as neural, immune and respiratory maturation.
      Epidemiological studies have convincingly demonstrated that the majority of
      asthma exacerbations, in both adults and children, follow viral upper respiratory
      tract infections. Asthma exacerbations are still often unresponsive to current
      asthma treatment, and new therapeutic approaches are required. This review
      presents current knowledge on the associations between infection and exacerbation
      of established asthma with respect to definitions, epidemiology, mechanisms and
      treatment.

PMID- 20675782
TI  - Bronchoscopy is useful for diagnosing smear-negative tuberculosis in HIV-infected
      patients.

PMID- 20675783
TI  - Sputum induction versus gastric washing for the diagnosis of pulmonary
      mycobacterial disease.

PMID- 20675784
TI  - In vivo imaging of pulmonary alveolar proteinosis using confocal endomicroscopy.

PMID- 20675785
TI  - Undiagnosed coeliac disease in patients with emphysema: a fortuitous association?

PMID- 20675786
TI  - Panic attacks in COPD and the somato-psycho-somatic feedback.

PMID- 20675787
TI  - Inspiratory muscle strength and Borg dyspnoea score.

PMID- 20675788
TI  - Do beta(2)-agonists inhibit capsaicin-induced cough?

PMID- 20675790
TI  - Implied body action directs spatial attention.
AB  - Research confirms that the body influences perception, but little is known about
      the embodiment of attention. We investigated whether the implied actions of
      others direct spatial attention, using a lateralized covert-orienting task with
      nonpredictive central cues depicting static, right/left-facing bodies poised in
      midaction. Validity effects (decreased response times for validly compared with
      invalidly cued trials) indicated orienting in the direction of the implied
      action. In Experiment 1, we compared action (running, throwing) with nonaction
      (standing) cues. Only the action cues produced validity effects, suggesting that
      implied action directs attention. The action cues produced faster responses
      overall, suggesting that action cues prime motor responses. In Experiment 2, we
      determined whether action cues shifted attention in a specific direction rather
      than to a general side of space: Two cues had similar action speed and motor
      effort but differed in implied direction (jumping, vertical; throwing,
      horizontal). Validity effects were found only for the throw cues for which the
      implied motion direction was consistent with lateralized target locations. In
      Experiment 3, we compared block-like stimuli to the throwing action stimuli to
      examine whether lower level perceptual information could account for the
      attention effects alone. Validity effects were found only for the human-action
      stimuli. Overall, the results suggest that predictive simulations of action shift
      attention in action-consistent directions.

PMID- 20675791
TI  - Recognizing famous people.
AB  - In daily life, face identification requires that the observer select a single
      representation from hundreds if not thousands in memory. This breadth of choice
      is nearly impossible to replicate in the laboratory using newly learned faces,
      especially in the context of a Bubbles experiment (Gosselin & Schyns, 2001). In
      this study, we obviated this concern by studying the performance of observers in
      a face-naming task using 210 faces of celebrities. On each trial, we presented a
      face randomly sampled with Bubbles. We performed least-square multiple linear
      regressions on the location of the samples and on accuracy to pinpoint the facial
      features that were used effectively in this task. Correct face identification
      relied primarily on the eye areas in spatial frequency bands ranging from 4.37 to
      70 cycles per face (cpf) and on the mouth and the nose in a spatial frequency
      band ranging from 8.75 to 17.5 cpf. A comparison with other studies (Caldara et
      al., 2005; Schyns, Bonnar, & Gosselin, 2002) in which Bubbles was used with a set
      of 10 newly learned faces revealed that although the eye areas were useful across
      studies, the mouth area and higher spatial frequencies gained in importance when
      few newly learned faces were used.

PMID- 20675792
TI  - A comparison of the McGurk effect for spoken and sung syllables.
AB  - The importance of visual cues in speech perception is illustrated by the McGurk
      effect, whereby a speaker's facial movements affect speech perception. The goal
      of the present study was to evaluate whether the McGurk effect is also observed
      for sung syllables. Participants heard and saw sung instances of the syllables
      /ba/ and /ga/ and then judged the syllable they perceived. Audio-visual stimuli
      were congruent or incongruent (e.g., auditory /ba/ presented with visual /ga/).
      The stimuli were presented as spoken, sung in an ascending and descending triad
      (C E G G E C), and sung in an ascending and descending triad that returned to a
      semitone above the tonic (C E G G E C#). Results revealed no differences in the
      proportion of fusion responses between spoken and sung conditions confirming that
      cross-modal phonemic information is integrated similarly in speech and song.

PMID- 20675794
TI  - Event-related potentials to overlapping shapes: effects of saliency and
      interference.
AB  - Visual perception is often challenged by various difficulties that act
      concomitantly and whose respective impacts may therefore be hard to distinguish.
      We used event-related potentials to dissociate the impact of target saliency,
      generated by occlusion, from that of interference produced by incongruent
      nontargets. In one block, the target (a square) partially occluded another square
      tilted by 45 degrees. This nontarget square interfered only to a small extent
      with target perception. In another block, the target was the occluded stimulus,
      and interference from the nontarget was substantial. Blocks including two kinds
      of overlapping shapes (a cross and a square) were added to control for the
      interference effect. Block comparisons revealed that occlusion modulated an
      occipital N250 and reaction times. In contrast, interference modulated a parietal
      N380 but not reaction times.

PMID- 20675793
TI  - Capture versus suppression of attention by salient singletons:
      electrophysiological evidence for an automatic attend-to-me signal.
AB  - There is considerable controversy about whether salient singletons capture
      attention in a bottom-up fashion, irrespective of top-down control settings. One
      possibility is that salient singletons always generate an attention capture
      signal, but this signal can be actively suppressed to avoid capture. In the
      present study, we investigated this issue by using event-related potential
      recordings, focusing on N2pc (N2-posterior-contralateral; a measure of
      attentional deployment) and Pd (distractor positivity; a measure of attentional
      suppression). Participants searched for a specific letter within one of two
      regions, and irrelevant color singletons were sometimes present. We found that
      the irrelevant singletons did not elicit N2pc but instead elicited Pd; this
      occurred equally within the attended and unattended regions. These findings
      suggest that salient singletons may automatically produce an attend-to-me signal,
      irrespective of top-down control settings, but this signal can be overridden by
      an active suppression process to prevent the actual capture of attention.

PMID- 20675795
TI  - Feature-based attention to unconscious shapes and colors.
AB  - Two experiments employed feature-based attention to modulate the impact of
      completely masked primes on subsequent pointing responses. Participants processed
      a color cue to select a pair of possible pointing targets out of multiple targets
      on the basis of their color, and then pointed to the one of those two targets
      with a prespecified shape. All target pairs were preceded by prime pairs
      triggering either the correct or the opposite response. The time interval between
      cue and primes was varied to modulate the time course of feature-based
      attentional selection. In a second experiment, the roles of color and shape were
      switched. Pointing trajectories showed large priming effects that were amplified
      by feature-based attention, indicating that attention modulated the earliest
      phases of motor output. Priming effects as well as their attentional modulation
      occurred even though participants remained unable to identify the primes,
      indicating distinct processes underlying visual awareness, attention, and
      response control.

PMID- 20675796
TI  - Involuntary transfer of a top-down attentional set into the focus of attention:
      evidence from a contingent attentional capture paradigm.
AB  - In the present study, we investigated whether involuntarily directing attention
      to a target-colored distractor causes the corresponding attentional set to enter
      a limited-capacity focus of attention, thereby facilitating the identification of
      a subsequent target whose color matches the same attentional set. As predicted,
      in Experiment 1, contingent attentional capture effects from a target-colored
      distractor were only one half to one third as large when subsequent target
      identification relied on the same (vs. a different) attentional set. In
      Experiment 2, this effect was eliminated when all of the target colors matched
      the same attentional set, arguing against bottom-up perceptual priming of the
      distractor's color as an alternative account of our findings. In Experiment 3,
      this effect was reversed when a target-colored distractor appeared after the
      target, ruling out a feature-based interference account of our findings. We
      conclude that capacity limitations in working memory strongly influence
      contingent attentional capture when multiple attentional sets guide selection.

PMID- 20675798
TI  - The impact of attention load on the use of statistical information and
      coarticulation as speech segmentation cues.
AB  - In two artificial language learning experiments, we investigated the impact of
      attention load on segmenting speech through two sublexical cues: transitional
      probabilities (TPs) and coarticulation. In Experiment 1, we observed that
      coarticulation processing was resilient to high attention load, whereas TP
      computation was penalized in a graded manner. In Experiment 2, we showed that
      encouraging participants to actively search for "word" candidates enhanced
      overall performance but was not sufficient to preclude the impairment of
      statistically driven segmentation by attention load. As long as attentional
      resources were depleted, independently of their intention to find these "words,"
      participants segmented only TP words with the highest TPs, not TP words with
      lower TPs. Attention load thus has a graded and differential impact on the
      relative weighting of the cues in speech segmentation, even when only sublexical
      cues are available in the signal.

PMID- 20675797
TI  - Voluntary attention increases perceived spatial frequency.
AB  - Voluntary covert attention selects relevant sensory information for prioritized
      processing. The behavioral and neural consequences of such selection have been
      extensively documented, but its phenomenology has received little empirical
      investigation. Involuntary attention increases perceived spatial frequency
      (Gobell & Carrasco, 2005), but involuntary attention can differ from voluntary
      attention in its effects on performance in tasks mediated by spatial resolution
      (Yeshurun, Montagna, & Carrasco, 2008). Therefore, we ask whether voluntary
      attention affects the subjective appearance of spatial frequency--a fundamental
      dimension of visual perception underlying spatial resolution. We used a demanding
      rapid serial visual presentation task to direct voluntary attention and measured
      perceived spatial frequency at the attended and unattended locations. Attention
      increased the perceived spatial frequency of suprathreshold stimuli and also
      improved performance on a concurrent orientation discrimination task. In the
      control experiment, we ruled out response bias as an alternative account by using
      a lengthened interstimulus interval, which allows observers to disengage
      attention from the cued location. In contrast to the main experiment, the
      observers showed neither increased perceived spatial frequency nor improved
      orientation discrimination at the attended location. Thus, this study establishes
      that voluntary attention increases perceived spatial frequency. This
      phenomenological consequence links behavioral and neurophysiological studies on
      the effects of attention.

PMID- 20675799
TI  - Working memory, perceptual priming, and the perception of hierarchical forms:
      opposite effects of priming and working memory without memory refreshing.
AB  - Previous research has shown that stimuli held in working memory (WM) can
      influence spatial attention. Using Navon stimuli, we explored whether and how
      items in WM affect the perception of visual targets at local and global levels in
      compound letters. Participants looked for a target letter presented at a local or
      global level while holding a regular block letter as a memory item. An effect of
      holding the target's identity in WM was found. When memory items and targets were
      the same, performance was better than in a neutral condition when the memory item
      did not appear in the hierarchical letter (a benefit from valid cuing). When the
      memory item matched the distractor in the hierarchical stimulus, performance was
      worse than in the neutral baseline (a cost on invalid trials). These effects were
      greatest when the WM cue matched the global level of the hierarchical stimulus,
      suggesting that WM biases attention to the global level of form. Interestingly,
      in a no-memory priming condition, target perception was faster in the invalid
      condition than in the neutral baseline, reversing the effect in the WM condition.
      A further control experiment ruled out the effects of WM being due to
      participants' refreshing their memory from the hierarchical stimulus display. The
      data show that information in WM biases the selection of hierarchical forms,
      whereas priming does not. Priming alters the perceptual processing of repeated
      stimuli without biasing attention.

PMID- 20675800
TI  - Response priming driven by local contrast, not subjective brightness.
AB  - We demonstrate qualitative dissociations of brightness processing in visuomotor
      priming and conscious vision. Speeded keypress responses to the brighter of two
      luminance targets were performed in the presence of preceding dark and bright
      primes (clearly visible and flanking the targets) whose apparent brightness
      values were enhanced or attenuated by a visual illusion. Response times to the
      targets were greatly affected by consistent versus inconsistent arrangements of
      the primes, relative to the targets (response priming). Priming effects could
      systematically contradict subjective brightness matches, such that one prime
      could appear brighter than the other but could prime as if it were darker.
      Systematic variation of the illusion showed that response-priming effects
      depended only on local flanker-background contrast, not on the subjective
      appearance of the flankers. Our findings suggest that speeded motor responses, as
      opposed to conscious perceptual judgments, access an early phase of lightness and
      brightness processing prior to full lightness constancy.

PMID- 20675801
TI  - Effective 3-D shape discrimination survives retinal blur.
AB  - A single experiment evaluated observers' ability to visually discriminate 3-D
      object shape, where the 3-D structure was defined by motion, texture, Lambertian
      shading, and occluding contours. The observers' vision was degraded to varying
      degrees by blurring the experimental stimuli, using 2.0-, 2.5-, and 3.0-diopter
      convex lenses. The lenses reduced the observers' acuity from -0.091 LogMAR (in
      the no-blur conditions) to 0.924 LogMAR (in the conditions with the most blur;
      3.0-diopter lenses). This visual degradation, although producing severe
      reductions in visual acuity, had only small (but significant) effects on the
      observers' ability to discriminate 3-D shape. The observers' shape discrimination
      performance was facilitated by the objects' rotation in depth, regardless of the
      presence or absence of blur. Our results indicate that accurate global shape
      discrimination survives a considerable amount of retinal blur.

PMID- 20675802
TI  - A hit-and-miss investigation of asymmetries in wheelchair navigation.
AB  - In contrast to the leftward inattention caused by right parietal damage, normal
      brain function shows a subtle neglect of the right and left sides in peripersonal
      and extrapersonal space, respectively. This study explored how these attentional
      biases cause healthy individuals to collide with objects on the right. In
      Experiment 1, participants navigated manual and electric wheelchairs through a
      narrow doorway. More rightward collisions were observed for the electric, but not
      the manual, wheelchair. Experiment 2 demonstrated that the rightward deviation
      for electric wheelchairs increased for wider doorways. Experiment 3 established
      that the rightward deviation is not the result of task-related vestibular input,
      using a remote control device to operate the wheelchair. The rightward deviation
      persisted in Experiment 4 when the doorway was removed, suggesting that the bias
      is the result of a mis-bisection of space. In Experiment 5, the rightward bias
      was replicated using an electric scooter, which is steered using handlebars.
      Finally, Experiment 6 required participants to point to the middle of the
      doorway, using a laser, before moving the scooter. Rightward mis-bisection was
      observed in both conditions. Rightward mis-bisection of lines in extrapersonal
      space provides the most parsimonious explanation of the rightward collisions and
      deviations.

PMID- 20675803
TI  - Differences in duration discrimination of filled and empty auditory intervals as
      a function of base duration.
AB  - In the present experiments, participants were presented with two time intervals
      that were marked by auditory signals, and their task was to decide which of the
      two was longer in duration. In Experiment 1, the base durations were 50 and 1,000
      msec, whereas in Experiment 2, seven different base durations ranging from 50 to
      1,000 msec were employed. It was found that filled intervals (continuous tones)
      were discriminated more accurately than empty intervals (with onset and offset
      marked by clicks) at the 50-msec base duration, whereas no performance
      differences could be shown for longer ones. The findings are consistent with the
      notion of a unitary timing mechanism that governs the timing of both filled and
      empty auditory intervals, independent of base durations. A likely conceptual
      framework that could explain better performance with filled as compared with
      empty intervals represents an information-processing model of interval timing
      that evolved from scalar timing theory. According to this account, a performance
      decrement observed with empty intervals may be due to a misassignment of pulses
      generated by an internal pacemaker.

PMID- 20675805
TI  - Alignment to visual speech information.
AB  - Speech alignment is the tendency for interlocutors to unconsciously imitate one
      another's speaking style. Alignment also occurs when a talker is asked to shadow
      recorded words (e.g., Shockley, Sabadini, & Fowler, 2004). In two experiments, we
      examined whether alignment could be induced with visual (lipread) speech and with
      auditory speech. In Experiment 1, we asked subjects to lipread and shadow out
      loud a model silently uttering words. The results indicate that shadowed
      utterances sounded more similar to the model's utterances than did subjects'
      nonshadowed read utterances. This suggests that speech alignment can be based on
      visual speech. In Experiment 2, we tested whether raters could perceive alignment
      across modalities. Raters were asked to judge the relative similarity between a
      model's visual (silent video) utterance and subjects' audio utterances. The
      subjects' shadowed utterances were again judged as more similar to the model's
      than were read utterances, suggesting that raters are sensitive to cross-modal
      similarity between aligned words.

PMID- 20675804
TI  - Language identification from visual-only speech signals.
AB  - Our goal in the present study was to examine how observers identify English and
      Spanish from visual-only displays of speech. First, we replicated the recent
      findings of Soto-Faraco et al. (2007) with Spanish and English bilingual and
      monolingual observers using different languages and a different experimental
      paradigm (identification). We found that prior linguistic experience affected
      response bias but not sensitivity (Experiment 1). In two additional experiments,
      we investigated the visual cues that observers use to complete the language
      identification task. The results of Experiment 2 indicate that some lexical
      information is available in the visual signal but that it is limited. Acoustic
      analyses confirmed that our Spanish and English stimuli differed acoustically
      with respect to linguistic rhythmic categories. In Experiment 3, we tested
      whether this rhythmic difference could be used by observers to identify the
      language when the visual stimuli is temporally reversed, thereby eliminating
      lexical information but retaining rhythmic differences. The participants
      performed above chance even in the backward condition, suggesting that the
      rhythmic differences between the two languages may aid language identification in
      visual-only speech signals. The results of Experiments 3A and 3B also confirm
      previous findings that increased stimulus length facilitates language
      identification. Taken together, the results of these three experiments replicate
      earlier findings and also show that prior linguistic experience, lexical
      information, rhythmic structure, and utterance length influence visual-only
      language identification.

PMID- 20675806
TI  - Attenuating the haptic horizontal-vertical curvature illusion.
AB  - In a number of experiments, blindfolded subjects traced convex curves whose
      verticals were equal to their horizontal extent at the base. Overestimation of
      verticals, as compared with horizontals, was found, indicating the presence of a
      horizontal-vertical illusion with haptic curves, as well as with visible curves.
      Experiment 1 showed that the illusion occurred with stimuli in the frontal plane
      and with stimuli that were flat on the table surface in vision and touch. In the
      second experiment, the stimuli were rotated, and differences between vision and
      touch were revealed, with a stronger illusion in touch. The haptic horizontal
      vertical illusion was virtually eliminated when the stimuli were bimanually
      touched using free exploration at the body midline, but a strong illusion was
      obtained when curves were felt with two index fingers or with a single hand at
      the midline. Bimanual exploration eliminated the illusion for smaller 2.5-
      through 10.2-cm stimuli, but a weakened illusion remained for the largest 12.7-cm
      patterns. The illusion was present when the stimuli were bimanually explored in
      the left and right hemispace. Thus, the benefits of bimanual exploration derived
      from the use of the two hands at the body midline combined with free exploration,
      rather than from bimanual free exploration per se. The results indicate the
      importance of haptic exploration at the body midline, where the body can serve as
      a familiar reference metric for size judgments. Alternative interpretations of
      the results are discussed, including the impact of movement-based heuristics as a
      causal factor for the illusion. It was suggested that tracing the curve's peak
      served to bisect the curve in haptics, because of the change in direction.

PMID- 20675807
TI  - Inhibition of vection by red.
AB  - We investigated the effects of colors on vection induction. Expanding optical
      flows during one's forward self-motion were simulated by moving dots. The dots
      and the background were painted in equiluminant red and green. Experiments 1 and
      2 showed that vection was weaker when the background was red than when the
      background was green. In addition, Experiment 3 showed that vection was weaker
      when the moving dots were red than when the dots were green. Experiment 4
      demonstrated that red dots on a red background induced very weak vection, as
      compared with green dots on a green background. In Experiments 5 and 6, we showed
      that the present results could not be explained by a luminance artifact.
      Furthermore, Experiment 7 showed that a moving red grating induced weaker vection
      than did a green one. We concluded that a red visual stimulus inhibits vection.

PMID- 20675808
TI  - Auditory, tactile, and multisensory cues facilitate search for dynamic visual
      stimuli.
AB  - Presenting an auditory or tactile cue in temporal synchrony with a change in the
      color of a visual target can facilitate participants' visual search performance.
      In the present study, we compared the magnitude of unimodal auditory,
      vibrotactile, and bimodal (i.e., multisensory) cuing benefits when the nonvisual
      cues were presented in temporal synchrony with the changing of the target's color
      (Experiments 1 and 2). The target (a horizontal or vertical line segment) was
      presented among a number of distractors (tilted line segments) that also changed
      color at various times. In Experiments 3 and 4, the cues were also made spatially
      informative with regard to the location of the visual target. The unimodal and
      bimodal cues gave rise to an equivalent (significant) facilitation of
      participants' visual search performance relative to a no-cue baseline condition.
      Making the unimodal auditory and vibrotactile cues spatially informative produced
      further performance improvements (on validly cued trials), as compared with cues
      that were spatially uninformative or otherwise spatially invalid. A final
      experiment was conducted in order to determine whether cue location (close to
      versus far from the visual display) would influence participants' visual search
      performance. Auditory cues presented close to the visual search display were
      found to produce significantly better performance than cues presented over
      headphones. Taken together, these results have implications for the design of
      nonvisual and multisensory warning signals used in complex visual displays.

PMID- 20675809
TI  - Somatotopic or spatiotopic? Frame of reference for localizing thermal sensations
      under thermo-tactile interactions.
AB  - The thermal sense is diffuse and incapable of providing precise spatial
      information. From a phenomenon known as thermal referral, we know that touch
      influences the localization of cold or warmth, leading to our perceiving illusory
      thermal sensations at a thermally neutral site. This study investigated the frame
      of reference for localizing thermal sensations under thermal referral in order to
      shed light on how thermal and tactile modalities coordinate to process
      localization information. One thermally neutral tactile stimulator and two cold
      (warm) stimulators were presented to different sets of three fingers of both
      hands. The location of the neutral tactile stimulator varied, and the strength of
      the referral was estimated from participants' performance in localizing the
      neutral tactile stimulator. By manipulating the somatotopic and spatiotopic
      distances between the stimulated sites, we found that the somatotopic distance-
      more specifically, the distance between and among the sites being defined in
      cortical topography--determines the strength of thermal referral. Our findings
      suggest that localization of thermal sensations under thermo-tactile interactions
      is processed with respect to the somatotopic frame of reference and that this
      cross-modal processing resides in early cortical areas whose organization
      conserves topographic information.

PMID- 20675810
TI  - Decomposing the Garner interference paradigm: evidence for dissociations between
      macrolevel and microlevel performance.
AB  - Three Garner interference experiments are described in which baseline, filtering,
      and correlated performance were assessed at both a macrolevel (condition average)
      and microlevel (intertrial contingency), using the pair-wise combinations of
      auditory pitch, loudness, and location. Discrepancies between pairs of dimensions
      were revealed between macro- and microlevel estimates of performance and, also,
      between filtering costs and correlated benefits, relative to baseline. The
      examination of the intertrial effects associated with filtering costs suggested
      that effects of increased stimulus uncertainty were mandatory, whereas effects of
      irrelevant variation were not. The examination of the intertrial effects
      associated with correlated benefits suggested that the detection of stimulus
      repetition took precedence over that of stimulus change. Violations of standard
      horse race accounts of processing did not appear to stem from differences in the
      absolute or relative speeds of processing between dimensions but, rather, from
      the special role that certain dimensions (e.g., pitch) may play in certain
      modalities (e.g., audition). The utility of examining repetition effects is
      demonstrated by revealing a level of understanding regarding stimulus processing
      typically hidden by aggregated measures of performance.

PMID- 20675811
TI  - Redundancy gains in simple responses and go/no-go tasks.
AB  - In divided-attention tasks with two classes of target stimuli, participants
      typically respond more quickly if both targets are presented simultaneously, as
      compared with single-target presentation (redundant-signals effect). Different
      explanations exist for this effect, including serial, parallel, and coactivation
      models of information processing. In two experiments, we investigated redundancy
      gains in simple and go/no-go responses to auditory-visual stimuli presented with
      an onset asynchrony. In Experiment 1, go/no-go discrimination was performed for
      near-threshold and suprathreshold stimuli. Response times in both the simple and
      go/no-go responses were well explained by a common coactivation model assuming
      linear superposition of modality-specific activation. In Experiment 2, the go/no
      go task was made more difficult. Participants had to respond to high-frequency
      tones or right-tilted Gabor patches and to withhold their response for low tones
      and left-tilted Gabors. Redundancy gains were consistent with coactivation
      models; however, channel-specific buildup of evidence seems to occur at different
      speeds in the two tasks. Response times of 1 participant support a serial self
      terminating model of modality-specific information processing. Supplemental
      materials for this article may be downloaded from http://app.psychonomic
      journals.org/content/supplemental.

PMID- 20675812
TI  - Dimensional overlap accounts for independence and integration of stimulus
      response compatibility effects.
AB  - Extensive studies have been conducted to examine various attentional control
      effects that stem from stimulus-stimulus (S-S) and stimulus-response (S-R)
      incompatibility. Among these behavioral paradigms, the best-known are the Stroop
      effect, the Simon effect, and Posner's cue validity effect. In this study, we
      designed two behavioral tasks incorporating these effects (Simon-color-Stroop and
      Simon-spatial-Stroop) guided by a general framework of S-R ensemble, the
      dimensional overlap theory. We analyzed various attentional effects according to
      dimensional overlaps among S-S and S-R ensembles and their combinations. We found
      that behavioral performance was independently affected by various dimensional
      overlaps in the Simon-color-Stroop task, whereas different sources of dimensional
      overlap in the Simon-spatial-Stroop task interacted with each other. We argue
      that the dimensional overlap theory can be extended to serve as a viable unified
      theory that accounts for diverse attentional effects and their interactions and
      helps to elucidate neural networks subserving attentional control.

PMID- 20675813
TI  - Cardiorespiratory responses to exercise in CHF: a conspiracy of maladaptation.

PMID- 20675814
TI  - Sparkling water--bicarbonate for cervix and cystic fibrosis.

PMID- 20675815
TI  - Exercise: not just a medicine for muscle?

PMID- 20675816
TI  - Realistic cardiac electrophysiology modelling: are we just a heartbeat away?

PMID- 20675819
TI  - The therapeutic effects of a mother's voice: Should selected aspects of family
      centered care be moved from the margins to the center?

PMID- 20675820
TI  - Manual turns in patients receiving mechanical ventilation.

PMID- 20675821
TI  - A second set of eyes: An introduction to Tele-ICU.

PMID- 20675822
TI  - Care of pediatric oncology patients after continuous hyperthermic peritoneal
      perfusion.

PMID- 20675824
TI  - Evaluation standards for management of artificial airways.

PMID- 20675825
TI  - Implementing a certification review on a shoestring budget.

PMID- 20675827
TI  - I am a critical care nurse.

PMID- 20675830
TI  - Social inclusion.

PMID- 20675829
TI  - Regulation of ABCG1 expression in human keratinocytes and murine epidermis.
AB  - ABCG1, a member of the ATP binding cassette superfamily, facilitates the efflux
      of cholesterol from cells to HDL. In this study, we demonstrate that ABCG1 is
      expressed in cultured human keratinocytes and murine epidermis, and induced
      during keratinocyte differentiation, with increased levels in the outer
      epidermis. ABCG1 is regulated by liver X receptor (LXR) and peroxisome
      proliferator-activated receptor-delta (PPAR-delta) activators, cellular sterol
      levels, and acute barrier disruption. Both LXR and PPAR-delta activators markedly
      stimulate ABCG1 expression in a dose- and time-dependent fashion. PPAR-gamma
      activators also increase ABCG1 expression, but to a lesser degree. In contrast,
      activators of PPAR-alpha, retinoic acid receptor, retinoid X receptor, and
      vitamin D receptor do not alter ABCG1 expression. In response to increased
      intracellular sterol levels, ABCG1 expression increases, whereas inhibition of
      cholesterol biosynthesis decreases ABCG1 expression. In vivo, ABCG1 is stimulated
      3-6 h after acute barrier disruption by either tape stripping or acetone
      treatment, an increase that can be inhibited by occlusion, suggesting a potential
      role of ABCG1 in permeability barrier homeostasis. Although Abcg1-null mice
      display normal epidermal permeability barrier function and gross morphology,
      abnormal lamellar body (LB) contents and secretion leading to impaired lamellar
      bilayer formation could be demonstrated by electron microscopy, indicating a
      potential role of ABCG1 in normal LB formation and secretion.

PMID- 20675831
TI  - Alcohol & drug abuse: Dual Diagnosis Anonymous of Oregon.
AB  - Many people with addictions report that support from peer groups fosters
      recovery. For people with co-occurring mental illnesses, dual-diagnosis peer
      support groups are considered helpful, but they are often unavailable. Recently,
      Dual Diagnosis Anonymous peer support groups have spread widely throughout Oregon
      as a complement to integrated dual diagnosis treatments. This column describes
      Dual Diagnosis Anonymous and its rapid implementation in Oregon.

PMID- 20675832
TI  - Personal accounts: Tall Paul.

PMID- 20675833
TI  - Trends in behavioral health care service provision by community health centers,
      1998-2007.
AB  - OBJECTIVE: The federal government boosted support for community health centers in
      medically underserved areas in 2002-2007. This investigation compared trends in
      behavioral health services provided by community health centers nationwide during
      the first several years of that initiative with immediately prior trends.
      METHODS: Data were extracted from the Health Resources and Services
      Administration's Uniform Data System on community health centers for 1998-2007
      (2007, N=1,067). Regression analyses revealed trends in individual community
      health centers' likelihood of providing on-site specialty mental health care,
      crisis services, and substance abuse treatment. Aggregate data were used to show
      national trends in numbers of behavioral health encounters, patients, and
      encounters per patient. RESULTS: The number of federally funded community health
      centers increased 43% between 2001 and 2007, from 748 to 1,067, over twice the
      annual growth rate between 1998 and 2001. However, trends in individual community
      health centers' likelihood of providing different types of behavioral health care
      were generally consistent across the two time periods. In 2007, 77% of community
      health centers offered specialty mental health services, 20% offered 24-hour
      crisis intervention services, and 51% offered substance abuse treatment. The mean
      number of mental health encounters per mental health patient at community health
      centers in 2007 was 2.9. CONCLUSIONS: The behavioral health care safety net has
      widened through rapid recent growth in the number of community health centers as
      well as a continuing increase in the proportion offering specialty mental health
      services.

PMID- 20675834
TI  - Impact of patient language proficiency and interpreter service use on the quality
      of psychiatric care: a systematic review.
AB  - OBJECTIVE: This literature review examined the effects of patients' limited
      English proficiency and use of professional and ad hoc interpreters on the
      quality of psychiatric care. METHODS: PubMed, PsycINFO, and CINAHL (Cumulative
      Index to Nursing and Allied Health Literature) were systematically searched for
      English-language publications from inception of each database to April 2009.
      Reference lists were reviewed, and expert sources were consulted. Among the 321
      articles identified, 26 met inclusion criteria: peer-reviewed articles reporting
      primary data on clinical care for psychiatric disorders among patients with
      limited proficiency in English or in the provider's language. RESULTS: Evaluation
      in a patient's nonprimary language can lead to incomplete or distorted mental
      status assessment. Although both untrained and trained interpreters may make
      errors, untrained interpreters' errors may have greater clinical impact,
      compromising diagnostic accuracy and clinicians' detection of disordered thought
      or delusional content. Use of professional interpreters may improve disclosure in
      patient-provider communications, referral to specialty care, and patient
      satisfaction. CONCLUSIONS: Little systematic research has addressed the impact of
      language proficiency or interpreter use on the quality of psychiatric care in
      contemporary U.S. settings. Findings are insufficient to inform evidence-based
      guidelines for improving quality of care among patients with limited English
      proficiency. Clinicians should be aware of the ways in which quality of care can
      be compromised when they evaluate patients in a nonprimary language or use an
      interpreter. Given U.S. demographic trends, future research should help guide
      practice and policy by addressing deficits in the evidence base.

PMID- 20675835
TI  - Lifestyle interventions for adults with serious mental illness: a systematic
      literature review.
AB  - OBJECTIVE: The promotion of healthy lifestyles among persons with serious mental
      illness is an integral part of their recovery. The aims of this systematic
      literature review were to rate the methodological quality of lifestyle
      intervention outcome studies for persons with serious mental illness, summarize
      intervention strategies, examine physical health outcomes, and evaluate the
      inclusion of racial and ethnic minority groups in these studies. METHODS:
      Electronic bibliographic database searches were performed to locate studies
      conducted in the United States. Articles written in English and published in peer
      reviewed journals between 1980 and 2009 were included. The authors used a
      standardized instrument to rate studies' methodological quality. RESULTS: Twenty
      three articles were reviewed. Based on studies' methodological quality, three
      levels of evidence were found: single-group reports, quasi-experimental studies,
      and randomized controlled trials. Most interventions used behavioral techniques
      to improve dietary habits and increase physical activity. Twelve studies reported
      significant improvements in either weight loss or metabolic syndrome risk factors
      associated with receiving a lifestyle intervention. Persons from racial and
      ethnic minority groups were underrepresented, especially Hispanics and Asian
      Americans. Only one study included non-English-speaking participants.
      CONCLUSIONS: Lifestyle interventions adapted to persons with serious mental
      illness show promise in reducing weight loss and some risk factors for metabolic
      syndrome. The underrepresentation of persons from racial or ethnic minority
      groups in this literature limits its generalizability. Implications for research
      and practice are discussed.

PMID- 20675836
TI  - Receipt of help after deliberate self-harm among adolescents: changes over an
      eight-year period.
AB  - OBJECTIVE: This study assessed whether there were any changes in receiving help
      after deliberate self-harm among adolescents over an eight-year period as a
      result of significant changes in service provision and media attention and, if
      so, whether individual predictors of receiving help may aid in explaining these
      changes. METHODS: School surveys among Norwegian adolescents in 1994 (N=7,446)
      and 2002 (N=11,678) asked identical questions about whether the students had
      experienced deliberate self-harm and, if so, whether they had received treatment
      or help from various health services, from informal sources, or from no one.
      RESULTS: Among the 1,401 students with valid responses who reported deliberate
      self-harm, 23% had received treatment or help from health services and 48% had
      received help from family or friends. These proportions increased significantly
      from 1994 to 2002, when individual predictors were controlled for. The number of
      sources from which help had been received also increased significantly over the
      period, whereas the proportion reporting no receipt of help or treatment from
      anyone decreased from 49% to 40%. A history of a suicide attempt increased the
      likelihood of receiving help, both from health services and from family or
      friends. Male gender and poorer parental attachment increased the likelihood of
      not having received any help or treatment after deliberate self-harm.
      CONCLUSIONS: Only about one in four adolescents seems to be reached by health
      services after deliberate self-harm. Yet the increase in the proportion receiving
      help from professional and informal sources over this period suggests that
      changes in societal factors may have reduced barriers for these vulnerable young
      people to seek help.

PMID- 20675837
TI  - Mental health care for children with disruptive behavior problems: a view inside
      therapists' offices.
AB  - OBJECTIVES: In the United States, more money is spent on treatment for children's
      mental health problems than for any other childhood medical condition, yet little
      is known about usual care treatment for children. Objectives of this study were
      to characterize usual care outpatient psychotherapy for children with disruptive
      behavior problems and to identify consistencies and inconsistencies between usual
      care and common elements of evidence-based practices in order to inform efforts
      to implement evidence-based practices in usual care. METHODS: Participants
      included 96 psychotherapists and 191 children aged four to 13 who were presenting
      for treatment for disruptive behavior to one of six usual care clinics. An
      adapted version of the Therapy Process Observational Coding System for Child
      Psychotherapy-Strategies scale (TPOCS-S) was used to assess psychotherapy
      processes in 1,215 randomly selected (out of 3,241 collected) videotaped
      treatment sessions; treatment sessions were recorded for up to 16 months.
      RESULTS: Most children received a large amount of treatment (mean number of
      sessions=22, plus children received other auxiliary services), and there was
      great variability in the amount and type of care received. Therapists employed a
      wide array of treatment strategies directed toward children and parents within
      and across sessions, but on average all strategies were delivered at a low
      intensity. Several strategies that were conceptually consistent with evidence
      based practices were observed frequently (for example, affect education and using
      positive reinforcement); however, others were observed rarely (for example,
      assigning or reviewing homework and role-playing). CONCLUSIONS: Usual care
      treatment for these youths reflected great breadth but not depth. The results
      highlight specific discrepancies between evidence-based care and usual care, thus
      identifying potentially potent targets for improving the effectiveness of usual
      care.

PMID- 20675838
TI  - A prospective examination of service use by abused and neglected children
      followed up into adulthood.
AB  - OBJECTIVE: This study sought to determine whether abused and neglected children
      are more likely than those without childhood maltreatment to use health and
      social services as adults and whether psychiatric status mediates or moderates
      the relationship. METHODS: A prospective cohort design was used. Individuals with
      documented cases of physical and sexual abuse and neglect (ages 0-10) and
      nonvictimized children matched on age, sex, and race-ethnicity were interviewed
      in adulthood (mean age 41 years). Past-year service use (general medical, mental
      health, substance abuse, and social) was assessed during 2003-2004 interviews
      (maltreated group, N=458; control group, N=349). Psychiatric status
      (posttraumatic stress disorder [PTSD], drug abuse, and major depressive disorder)
      was assessed during 1989-1995 (mean age 29) by structured interview. RESULTS:
      Individuals with histories of childhood abuse and neglect were significantly more
      likely than their control group counterparts to use mental health services (odds
      ratio [OR]=1.60, 95% confidence interval [CI]=1.04-2.45) and social services
      (OR=2.95, CI=2.19-3.97) in adulthood. Psychiatric status in young adulthood (PTSD
      and major depressive disorder) partially mediated the relationship between
      childhood maltreatment and use of mental health services, whereas major
      depression and drug abuse moderated the relationship between maltreatment and use
      of any services and general medical services. CONCLUSIONS: In adulthood,
      individuals with documented histories of childhood abuse and neglect are more
      likely than persons without such histories to use some types of services, and
      psychiatric status mediates and moderates these relationships. Findings have
      implications for the provision of services to persons with childhood abuse and
      neglect.

PMID- 20675839
TI  - Trends in recognition of and service use for attention-deficit hyperactivity
      disorder in Britain, 1999-2004.
AB  - OBJECTIVE: National data suggest that attention-deficit hyperactivity disorder
      (ADHD) is underdiagnosed in Britain and that parental factors determine service
      use. This situation may have changed in recent years following policy and
      research recommendations. This study investigated changes in rates and correlates
      of service use for ADHD in Britain between 1999 and 2004. METHODS: Use of various
      services by children aged five to 16 with ADHD (N=176) who were identified in the
      cross-sectional, nationally representative 2004 British Child and Adolescent
      Mental Health Survey was examined. The 2004 sample was compared with a community
      sample identified in a similar survey conducted in 1999. RESULTS: Most parents
      (90%) of children with ADHD recognized the presence of a problem, and 55% thought
      that their child had hyperactivity. Past-year contacts with education-based
      professionals exceeded those with professionals in specialist health services
      (74% versus 51%). One-third of children with ADHD were taking medication. Child
      factors, including severity of ADHD and a comorbid emotional or behavioral
      disorder, were the main determinants of service use. Parental burden was also
      associated with specialist service use. Specialist service use increased over
      five years after adjustment for severity and parental perceptions and burden
      (odds ratio=1.76, 95% confidence interval=1.13-2.75, p=.013). CONCLUSIONS:
      Barriers to care for ADHD in Britain appear to have been reduced in recent years.
      Medication for ADHD appears to be used cautiously, and the study found little
      empirical evidence of overuse. There is a need for health services to provide
      training and support for education-based professionals to help them recognize and
      manage children with ADHD.

PMID- 20675840
TI  - Stigmatizing experiences of parents of children with a new diagnosis of ADHD.
AB  - OBJECTIVE: The experiences of parents of a child who received an initial
      diagnosis of attention-deficit hyperactivity disorder (ADHD) were examined to
      determine the ways in which they may have encountered stigmatizing situations.
      METHODS: Forty-eight parents of children aged six to 18 years were interviewed
      about their experiences leading up to their child's ADHD diagnosis, including
      their decisions to seek treatment. All interviews were recorded, transcribed, and
      analyzed using grounded theory methods. Codes were identified using a constant
      comparative approach, which led to theoretically defined thematic constructs of
      stigma. RESULTS: Stigmatizing experiences were noted by 77% of the sample. Nearly
      half (N=21, 44%) were concerned about how society would label their child, 40%
      (N=19) felt social isolation and rejection, and 21% (N=10) perceived health care
      professionals and school personnel as being dismissive of their concerns.
      Parents' own attitudes about ADHD treatment were shaped by their exposure to
      negative media (N=10, 21%), their mistrust of medical assessments (N=8, 17%), and
      the influence of general public views (N=3, 6%). These stigmatizing views were
      related to parental concerns about the impact that diagnosis and treatment would
      have on their child's self-esteem and opportunities for future success.
      CONCLUSIONS: The range of ways in which parents in the study experienced stigma
      highlights the need for multiple perspectives for community outreach and public
      health programs that are aimed at addressing and eliminating mental health
      stigma. Even though stigma is a well-established barrier to mental health service
      use, the anticipated benefits of treatment may outweigh parents' experiences with
      stigma.

PMID- 20675841
TI  - Perspectives on adolescent residential substance abuse treatment: when are
      adolescents done?
AB  - OBJECTIVES: The study evaluated responses from adolescents in substance abuse
      treatment, their parents, and treatment staff to the question of what constitutes
      treatment success. METHODS: Semistructured interviews were conducted with 28
      adolescents, 30 parents, and 29 staff at three residential substance abuse
      treatment programs in two states. Data were coded and organized into themes by
      respondent type. RESULTS: Respondents reported knowing when treatment was no
      longer needed based on changes in adolescents' substance use, treatment-related
      and other behaviors, and attitudes and character. A fourth category of responses
      indicated respondents' ambiguity regarding successful completion of substance
      abuse treatment. Little concurrence was found among adolescents, parents, and
      treatment center staff to indicate criteria suggesting that discharge is
      appropriate. CONCLUSIONS: Substance abuse treatment programs and their clients
      may benefit from ensuring that staff, parents, and adolescents are aware of
      treatment goals to promote more effective treatment and improve collaboration
      toward the adolescent's recovery.

PMID- 20675842
TI  - Age of diagnosis among Medicaid-enrolled children with autism, 2001-2004.
AB  - OBJECTIVE: This study examined child- and county-level factors associated with
      age of diagnosis of autism among Medicaid-enrolled children and the change in age
      of diagnosis over time. METHODS: National Medicaid claims from 2002 to 2004 were
      used to identify age of diagnosis and characteristics of children younger than
      ten years old with a diagnosis of autism (ICD-9 codes 299, 299.0x, or 299.8x).
      These data were linked to county-level education and health care variables.
      Linear regression with random effects for state and county was used to examine
      associations between these variables and age of diagnosis. RESULTS: A total of
      28,722 Medicaid-enrolled children newly diagnosed with an autism spectrum
      disorder were identified. Their average age of diagnosis was 64.9 months.
      Adjusted average age of diagnosis dropped 5.0 months for autistic disorder and
      1.8 months for other spectrum disorders during the study period. Asian children
      were diagnosed earlier than children in other racial or ethnic groups, although
      these differences were much more pronounced for other spectrum disorders than for
      autistic disorder. Children eligible for Medicaid through the poverty category
      were diagnosed earlier, on average, than children who were eligible through
      disability, foster care, or other reasons, although this difference decreased
      over time. Children in large urban or rural counties were diagnosed later than
      children in small urban or suburban counties. CONCLUSIONS: Findings showed that
      diagnosis of autism occurs much later than it should among Medicaid-enrolled
      children, although timeliness is improving over time. Analyses suggest that most
      of the observed variation is accounted for by child-level variables, rather than
      county-level resources or state policies.

PMID- 20675843
TI  - Health insurance coverage among persons with schizophrenia in the United States.
AB  - OBJECTIVE: This study estimated the rates of health insurance coverage in the
      U.S. civilian noninstitutionalized population with schizophrenia and assessed
      whether basic access to health care varied across health insurance categories.
      METHODS: Data from the Medical Expenditures Panel Survey collected between 2002
      and 2006 were used. RESULTS: The sample contained 328 records representing
      493,006 noninstitutionalized civilian persons with schizophrenia. Eighty-seven
      percent had Medicaid or Medicare, 8% received care through the Veterans Health
      Administration, and 15% had private insurance for at least one day during the
      year. About 7% were uninsured all of the year. The uninsured tended to be male
      (92%), nonwhite (54%), and unmarried (97%), and 30% of the uninsured had not had
      a medical checkup in more than five years. CONCLUSIONS: Almost all U.S. adults
      with schizophrenia were found to receive government health insurance, yet a
      measurable minority remained uninsured. These national estimates highlight
      opportunities for improving health service delivery for this vulnerable
      population.

PMID- 20675844
TI  - Criminal justice involvement of armed forces veterans in two systems of care.
AB  - OBJECTIVE: This study compared criminal justice involvement of veterans before
      and after receiving services from community-based programs of the Veterans Health
      Administration (VHA) (N=1,640) or a state Department of Mental Health (DMH) (N=
      693). METHODS: Anonymous extracts from VHA, DMH, and statewide criminal charging
      databases were analyzed by probabilistic population estimation to determine
      criminal charging rates in the years before and after the year of service receipt
      in each system of care. RESULTS: Veterans who received DMH services experienced a
      greater reduction in the rate of criminal charging than veterans who received VHA
      services (43% and 17% reductions). For veterans with co-occurring mental and
      substance use disorders, rates were reduced 33% among VHA service recipients,
      whereas they increased 48% among DMH service recipients. CONCLUSIONS: These
      differences indicate that the design of veterans' behavioral health service
      delivery systems would benefit from cross-sector outcome measures that complement
      clinical measures such as those used nationally by the VHA.

PMID- 20675845
TI  - A feasibility study of the use of asynchronous telepsychiatry for psychiatric
      consultations.
AB  - OBJECTIVE: This study examined the feasibility of conducting psychiatric
      consultations using asynchronous, or store-and-forward, video-based
      telepsychiatry. METHODS: Video-recorded 20- to 30-minute assessments of 60
      nonemergency, English-speaking adult patients in a medically underserved county
      in California were uploaded along with other patient data to a Web-based record.
      Two psychiatrists then used the record to provide psychiatric consultations to
      the referring primary care providers. RESULTS: Eighty-five percent of patients
      received diagnoses of mood disorders, 32% diagnoses of substance use disorders,
      53% diagnoses of anxiety disorders, and 5% other axis I diagnoses. Psychiatrists
      recommended short-term medication changes for 95% of the patients and provided
      guidelines for possible future changes. CONCLUSIONS: This study-the first study
      of asynchronous telepsychiatry to be published-demonstrated the feasibility of
      this approach. This type of assessment should not replace the face-to-face
      psychiatric interview, but it may be a very helpful additional process that
      improves access to care and expertise.

PMID- 20675846
TI  - Co-occurring disorders and learning difficulties: client perspectives from two
      community-based programs.
AB  - OBJECTIVE: This study explored the experiences of adults with learning
      disabilities in the mental health system. METHODS: Thirty-seven participants were
      clients at one of two community-based mental health agencies. Participants
      completed a standardized tool for assessment of a possible learning difficulty.
      Nineteen individuals met criteria, and nine participated in semistructured
      interviews. RESULTS: The quantitative results indicated that participants were
      challenged by limited education, long-term mental illness, and homelessness.
      Qualitative themes concerned challenges in the areas of job skills, education,
      comprehension of paperwork, housing, social skills, comprehension of agency
      literature, low self-esteem, and accessing services. CONCLUSIONS: The findings
      may help inform social service providers about the service gap between the
      education and mental health systems. People with co-occurring disorders and
      learning disabilities represent a segment of the treatment population that may
      experience limited access to social services without modifications to service
      delivery.

PMID- 20675847
TI  - Changes in prescription of psychotropics after an earthquake in Italy.

PMID- 20675848
TI  - Recovery-oriented care and choice.

PMID- 20675850
TI  - Effects of low-dose infliximab on spinal inflammation on magnetic resonance
      imaging in ankylosing spondylitis.

PMID- 20675851
TI  - Beyond early diagnosis: occult psoriatic arthritis.

PMID- 20675852
TI  - Are there patients with inflammatory disease who do not respond to prednisone?

PMID- 20675853
TI  - Lupus related longitudinal myelitis.

PMID- 20675854
TI  - Development of anti-CCP-positive rheumatoid arthritis following pegylated
      interferon-alpha2a treatment for chronic hepatitis C infection.

PMID- 20675855
TI  - Multifocal motor neuropathy with conduction block following treatment with
      infliximab.

PMID- 20675856
TI  - Successful treatment with infliximab of a patient with tumor necrosis factor
      associated periodic syndrome (TRAPS) who failed to respond to etanercept.

PMID- 20675857
TI  - Rituximab treatment in a child with rosai-dorfman disease and systemic lupus
      erythematosus.

PMID- 20675858
TI  - Reactivated varicella zoster virus may cause peripheral arterial thrombosis.

PMID- 20675859
TI  - Coexistent Wegener's granulomatosis and Goodpasture's disease.

PMID- 20675860
TI  - SET7/9 catalytic mutants reveal the role of active site water molecules in lysine
      multiple methylation.
AB  - SET domain lysine methyltransferases (KMTs) methylate specific lysine residues in
      histone and non-histone substrates. These enzymes also display product
      specificity by catalyzing distinct degrees of methylation of the lysine epsilon
      amino group. To elucidate the molecular mechanism underlying this specificity, we
      have characterized the Y245A and Y305F mutants of the human KMT SET7/9 (also
      known as KMT7) that alter its product specificity from a monomethyltransferase to
      a di- and a trimethyltransferase, respectively. Crystal structures of these
      mutants in complex with peptides bearing unmodified, mono-, di-, and
      trimethylated lysines illustrate the roles of active site water molecules in
      aligning the lysine epsilon-amino group for methyl transfer with S
      adenosylmethionine. Displacement or dissociation of these solvent molecules
      enlarges the diameter of the active site, accommodating the increasing size of
      the methylated epsilon-amino group during successive methyl transfer reactions.
      Together, these results furnish new insights into the roles of active site water
      molecules in modulating lysine multiple methylation by SET domain KMTs and
      provide the first molecular snapshots of the mono-, di-, and trimethyl transfer
      reactions catalyzed by these enzymes.

PMID- 20675861
TI  - Isoform-specific intermolecular disulfide bond formation of heterochromatin
      protein 1 (HP1).
AB  - Three mammalian isoforms of heterochromatin protein 1 (HP1), alpha, beta, and
      gamma, play diverse roles in gene regulation. Despite their structural
      similarity, the diverse functions of these isoforms imply that they are
      additionally regulated by post-translational modifications. Here, we have
      identified intermolecular disulfide bond formation of HP1 cysteines in an isoform
      specific manner. Cysteine 133 in HP1alpha and cysteine 177 in HP1gamma were
      involved in intermolecular homodimerization. Although both HP1alpha and HP1gamma
      contain reactive cysteine residues, only HP1gamma readily and reversibly formed
      disulfide homodimers under oxidative conditions. Oxidatively dimerized HP1gamma
      strongly and transiently interacted with TIF1beta, a universal transcriptional co
      repressor. Under oxidative conditions, HP1gamma dimerized and held TIF1beta in a
      chromatin component and inhibited its repression ability. Our results highlight a
      novel, isoform-specific role for HP1 as a sensor of the cellular redox state.

PMID- 20675862
TI  - Giant Cell Tumor (tumor gigantocellularis, osteoclastoma) - epidemiology,
      diagnosis, treatment.
AB  - The author presents the epidemiology, classification, clinical features and
      strategies of treatment of Giant Cell Tumor. Giant Cell Tumor of Bone accounts
      for 4-8% of primary bone tumors. It is most commonly seen in women aged 20 to 40
      years. The most common sites are the distal femur and proximal tibia, distal
      radius, and proximal humerus. Increasing pain at the tumor site is the most
      common presenting symptom. Three types of GCT can be distinguished
      radiographically according to the Cappanacci or Enneking classification. The
      mainstay of treatment is total mechanical removal with curettage. The recurrence
      rate is high (12-50%) during the first 2-3 years after surgery, regardless of pre
      operative tumor stage. 5-7% cases of giant cell tumor produce malignant
      recurrences, usually after five to more than 10 years after surgery.

PMID- 20675863
TI  - The results of arthroscopic capsular release in the treatment of frozen shoulder 
      two-year follow-up.
AB  - BACKGROUND: The term frozen shoulder refers to an inflammatory condition
      characterized by pain and reduced range of passive and active motion of the
      shoulder. Initial management is mostly conservative. In some cases, however,
      invasive treatment is necessary. Given the dearth of available data on long-term
      operative outcomes, it appears interesting to present a comprehensive discussion
      of this issue. The aim of this study was to evaluate the improvement of range of
      motion and function of the affected shoulder after a minimum of two-year follow
      up following arthroscopic capsular release of idiopathic and posttraumatic frozen
      shoulder. MATERIAL AND METHODS: The study enrolled 30 patients with frozen
      shoulder, including 16 patients with idiopathic FS and 14 patients with
      posttraumatic frozen shoulder. All patients had an anteroinferior capsular
      release and three additionally had a posterior capsulotomy. After a minimum of
      two-years of follow-up, the shoulder's range of motion and limb function were
      evaluated according to a modified version of the Constant-Murley Score (0-75),
      the ASES (American Shoulder and Elbow Surgeons) score and a subjective scale
      designed by the authors. RESULTS: The improvement in the range of motion after
      arthroscopic capsular release was considerable and statistically significant
      (p<0.05) compared to pre-operative values both intraoperatively and after a
      minimum of two years of follow-up in both groups and across all planes of
      movement tested. The improvement of function of the shoulder after a minimum two
      years following arthroscopic capsular release was significant (p<0.05) according
      to the Constant-Murley score (from 19.3 preoperatively to 65.9 postoperatively, 0
      75) and the ASES score (from 22.8 preoperatively to 92.7 postoperatively, 0-100).
      CONCLUSION: Arthroscopic capsular release significantly improved the range of
      motion and function in idiopathic and posttraumatic frozen shoulder.

PMID- 20675864
TI  - Comparative analysis of analgesic efficacy of selected physiotherapy methods in
      low back pain patients.
AB  - BACKGROUND: Low back pain syndromes are one of the most frequent causes of
      movement limitation in populations of highly industrialized countries. They are
      listed as the main cause of inability to work among people of working age.
      Chronic pain and the associated limitation of movement underlie the quest for
      effective therapies. The use of ultrasound, LLLT, vacuum therapy with Ultra Reiz
      current in physical therapy of these patients prompts research over their
      effectiveness in the therapy of patients with low-back pain. The aim of the work
      was to evaluate the analgesic efficacy of LLLT, ultrasound, and vacuum therapy
      with Ultra Reiz current in patients with low back pain. MATERIAL AND METHODS: The
      study involved 94 people divided into three groups (A,B,C). Group A (n=35)
      received a series of 10 low energy laser therapy sessions (wave length 808 nm,
      surface density of radiation 510 mW/cm(2), continuous wave form, scanning mode, a
      dose of 12 J/cm(2) on a surface of 100 cm(2) [10x10cm]). Patients in Group B
      (n=27) had ultrasound sessions with a wave intensity of 1 W/cm(2) for 3 minutes.
      Patients in Group C (n=32) underwent vacuum therapy (8 kPa) combined with Ultra
      Reiz current. Subjective pain assessment was carried out using a modified Latinen
      questionnaire and a visual analogue scale of pain intensity. Lumbosacral spine
      mobility was evaluated with the Schober test and the finger-to- floor test.
      RESULTS: In Group A, following low energy laser therapy, a statistically
      significant decrease in pain intensity was observed, together with decreased
      analgesic consumption compared to the other groups. In Group C, following vacuum
      therapy combined with Ultra Reiz currents, a significant decrease in the
      frequency of pain was observed together with increased physical activity compared
      to both Groups A and B, assessed according to a modified Laitinen pain indicator
      questionnaire. The biggest improvement in global spine mobility and lumbosacral
      flexion was observed in Group C (vacuum therapy plus Ultra Reiz current) compared
      to the other groups. However, the most significant improvement in lower spine
      extension was noted in Group B (ultrasound). CONCLUSIONS: 1. The study showed
      slightly higher analgesic efficacy of laser biostimulation in comparison to
      vacuum therapy combined with Ultra Reiz current in patients with low back pain.
      2. A more prominent increase in lumbosacral spine mobility was observed after
      vacuum therapy combined with Ultra Reiz current and ultrasound therapy.

PMID- 20675865
TI  - Cementless hip joint alloplasty complicated by intraoperative fracture of the
      femoral bone.
AB  - BACKGROUND: The aim of the study was to analyse the outcomes of hip replacement
      complicated by intraoperative femoral fractures and to analyse their effective
      management. MATERIALS AND METHODS: The medical records of 43 cases of
      intraoperative femoral fractures (1.4% of all hip replacements) were
      retrospectively reviewed. The patient group included 29 females. Patients' age
      ranged from 20 to 66 years (mean age: 48.4 years). Follow-up duration ranged from
      8 to 89 months (mean duration: 44 months). RESULTS: There were 13 fractures of
      the greater trochanter, 21 fractures of the lesser trochanter involving the
      calcar, 7 at the implant stem level, and two below the implant stem. In 3 cases,
      the fracture was treated with a revision stem, with cerclage used in 17 other
      cases. In the remaining cases, the fractures were stable and did not require any
      internal fixation. Eighteen patients had very good final results, 19 had good and
      6, fair results, according to Merle D'Aubigne- Postel's classification in
      Charnley's modification. None of our patients demonstrated evidence of stem
      loosening at the final follow-up. CONCLUSIONS: Unstable intraoperative femoral
      fractures during a hip replacement procedure are rare and occur mostly in
      patients with post-dysplastic hips with a narrow intramedullary canal. In cases
      of stable fractures of the trochanter and calcar region, 12 weeks of partial
      weight bearing without additional immobilization is a sufficient approach. The
      final results are satisfactory in most cases of intraoperative femoral fractures.

PMID- 20675866
TI  - Tibio-talo-calcaneal arthrodesis by a retrograde intramedullary nail.
AB  - BACKGROUND: The paper presents the results of tibio-talo-calcaneal fusions using
      Retrograde Nailing System and Bone Grafting. MATERIAL AND METHODS: From May 2006
      to January 2008, we performed 13 fusions in 11 consecutive patients with advanced
      ankle and hindfoot disease. Patients underwent 13 tibiotalocalcaneal fusions (2
      patients had initial tibiotalocalcaneal fusion using screws and subsequently
      developed a non-union) and all 11 patients were available for follow up. The
      procedure was performed unilaterally in all cases; there were 4 males and 7
      females. The average age at the time of surgery was 65.25 years (range 51-81
      years). The average duration of follow-up was 8 months (range between 6-15
      months). RESULTS: Solid fusion was achieved in all 11 cases. The average AOFAS
      score (maximum 78 points) improved from a pre-operative mean of 16 points [range
      3 to 29] to a mean of 54 points [range 42 to 70], excluding the scores for
      stability and range of motion. Patient satisfaction scale (maximum 10 points)
      improved from 3 to 7 in both pain and function. CONCLUSIONS: 1- Arthrodesis
      should be considered only after all conservative treatments fails; it is one of
      the most challenging surgical procedures that must be undertaken with care in
      order to provide the best possible outcome. 2- Thorough evaluation and
      examination will help the surgeon to find the correct indication and identify
      patients who are not suitable for the procedure. It is crucial to assess the
      vascular and neurological status and to obtain weight-bearing radiographs
      (possibly CT) of the ankle to evaluate the deformity. 3- The optimal position of
      the ankle is in neutral flexion, 0-5 degrees valgus, and 10 degrees external
      rotation, similar to the contralateral foot and posterior translation of the
      talus under the tibia (5mm). 4- Tibio-talo-calcaneal fusion with retrograde
      nailing and bone grafting is a successful salvage procedure in severe ankle and
      hind foot arthrosis with deformity.

PMID- 20675867
TI  - Habitual dislocation of the hip in neurofibromatosis type 1. Case study.
AB  - A 15-year-old boy with neurofibromatosis type 1 developed habitual dislocation of
      the right hip. No intraarticular pathology could be found in imaging studies. The
      dislocation became fixed during the follow-up.

PMID- 20675868
TI  - Diastematomyelia - a diagnostic and therapeutic problem. Case study.
AB  - BACKGROUND: Diastematomyelia is a type of dysraphism with a double or bifid
      spinal cord divided by an osseous septum. This defect often co-occurs with other
      developmental disorders of the skull or the atlanto-occipital junction. The
      course may be benign or aggressive. 2. CASE REPORTS: We describe two female
      patients treated in the Rehabilitation Clinic and the Orthopaedic Department at
      the Medical University of Lublin in the years 2004 - 2009. The first patient was
      diagnosed at the age of 20 years to have diastematomyelia at the L3 level and
      spina bifida occulta at L1- S5 and at the C1 arch. In the other patient,
      diastematomyelia at the L3 level and spondylolisthesis at L5-S1 were found at the
      age of 14 years. Initially both patients were treated for lumbosacral radicular
      syndromes. Physiotherapy intensified the pain. The patient with diastematomyelia
      and L5-S1 spondylolisthesis had L5-S1 segment stabilization performed at the age
      of 16. The pain subsided after the surgery. The other patient was instructed to
      stop rehabilitation, follow a balanced lifestyle, and refrain from physical work,
      which eliminated the pain. DISCUSSION: Managing a patient with diastematomyelia
      demands caution. Diagnosis of this defect requires a thorough cause-and-effect
      analysis of the presenting signs and symptoms of spinal dysfunction. The
      treatment should be dependent on local pain intensity (which is often not
      directly associated with the disorder) and on the degree of neurological
      dysfunction. 5. CONCLUSIONS: 1. A thorough clinical evaluation with spinal
      imaging prior to elective surgery for scoliosis and other spine deformities
      should be a standard procedure undertaken in order to avoid complications. 2. The
      treatment for diastematomyelia should depend on the intensity of local pain and
      on the level of neurological dysfunction. 3. Broadly understood rehabilitation is
      not always effective, often increasing the pain and/or neurological complaints.

PMID- 20675869
TI  - Assesment scores of functional efficiency in hip osteoathritis.
AB  - One of the fundamental problem to solved, connected with a way of proceeding in
      hip osteoarthritis is appropriate selection of diagnosis methods. Various scores
      helps in assessment of functional efficiency of the hip. They are applied on
      variable stages of diagnosis process, assumed way of treatment included
      physiotherapy and to analysis achieved results of treatment. Universal applied
      scores are: HHS, WOMAC, Merle D'Aubigne-Postel, Mayo. The purpose of this study
      was to compare methods mentioned above. The special attention was paid to an
      assessment of usefulness of scores in treatment process.

PMID- 20675870
TI  - [Treatment strategy of Alzheimer's disease: pause in clinical trials of Abeta
      vaccine and next steps].
AB  - The important pathognomonic features of Alzheimer disease (AD) brain are the
      occurrence of abundant neurofibrillary tangles (NFTs) in neurons and presence of
      extracellular deposits of beta-amyloid (Abeta)- senile plaques. In the early
      1980s, the NFTs were characterized, and cerebral amyloid was purified; further
      the amino acid sequences of the tau protein in the NFTs and of Abeta were
      identified. Immunohistochemical studies with antibodies to tau and Abeta revealed
      that extracellular accumulation of Abeta precedes that of tau in neurons.
      Molecular genetic studies revealed that abnormal gene mutations of familial AD
      accelerate Abeta production. On the basis of these findings, the amyloid cascade
      hypothesis that Abeta accumulation is the primary cause of neuronal degeneration
      and induces accumulation of tau in the AD brain was proposed and widely accepted.
      Thus, on the basis of this hypothesis, transgenic AD mice were treated with Abeta
      vaccine; the Abeta amyloid plaques were eliminated, and a dramatic improvement of
      the behavioral deficits was observed in the treated mice. The great success of
      preclinical studies promoted clinical trials of the Abeta vaccine in AD patients.
      However,the clinical trials were discontinued because of the occurrence of severe
      meningoencephalitis. Postmortem examination of the brains of the vaccinated
      patients with high titer of the anti- Abeta antibody in the serum revealed
      elimination of the Abeta plaques along with presence of cerebral inflammation.
      However, in autopsy-proven cases, assessment of the clinical and cognitive
      functions of the patients did not provide any evidence for improved survival or
      prolongation of the time to severe dementia. Thus, anti-Abeta antibody could
      eliminate the accumulated Abeta but could not rescue the degenerated neurons.
      Thus, the AD treatment strategy should be converted from repair and cure of AD to
      prevention. Anti-Abeta therapy must be started at the preclinical stage, and it
      is necessary to focus on tau and other proteins, mitochondria, glial cells, and
      other factors that influence the degeneration of neurons.

PMID- 20675871
TI  - [Alzheimer's disease in Japan and other countries: review of epidemiological
      studies in the last 10 years].
AB  - Alzheimer disease (AD) is the most common type of dementia. In this review
      article, we summarized the current findings concerning the prevalence and
      incidence of AD in Japan and other countries; these findings were reported in the
      last 10 years. The prevalence of dementia among individuals aged more than 65 and
      more than 75 years was 2.4%-8.4% and 15.8%, respectively; this was determined
      according to the DSM-IV or DSM-III-R criteria. Further, the worldwide ratio of AD
      and vascular dementia (VaD) was 1.8-4.8, which was calculated according to the
      NINCDS-ADRDA and NINDS-AIREN criteria. In Japan, the prevalence of dementia among
      individuals aged more than 65 years was 3.8%-11.0%; this value was calculated
      according to the DSM-IV or DSM-III-R criteria. Further, the AD/VaD ratio among
      these individuals was 2.1-4.1, which was calculated according to the NINCDS-ADRDA
      and NINDS-AIREN. The prevalence of dementia and the AD/VaD ratios vary widely
      among the previous reports. The reasons for this are variations in the diagnostic
      criteria, epidemiological methods, demographics caused by the aging population,
      and mortality rate. It is necessary to establish a standard international
      epidemiological method worldwide. In addition, the diagnostic criteria of other
      types of dementias such as dementia with Lewy bodies and idiopathic normal
      pressure hydrocephalus should be considered.

PMID- 20675872
TI  - [Risk factors for Alzheimer's disease].
AB  - Alzheimer disease (AD) is the most common cause of dementia in elderly patients.
      Identification of risk factors for AD would contribute to the understanding of AD
      pathogenesis and thus, help in the development of preventive methods. Early-onset
      familial AD is associated with mutations of the genes encoding amyloid precursor
      protein (APP), presenilin 1 (PS-1), or PS-2, resulting in the overproduction of
      amyloid beta-protein. Epidemiological and case-control studies have led to the
      identification of several risk factors for sporadic AD. The most concrete genetic
      risk factor for AD is the epsilon4 allele of apolipoprotein E gene (APOE). In
      addition, several genes such as CTNNA3, GAB2, PVRL2, TOMM40, and APOC1 are known
      to be the risk factors that contribute to AD pathogenesis. On the other hand,
      nongenetic risk factors, such as age, sex, alcohol consumption, smoking,
      depression, head injury, and nutrition have also been reported. Although aging is
      the strongest risk factor for AD, the mechanisms underlying the development of AD
      as a result of ageing remain to be elucidated.

PMID- 20675873
TI  - [Involvement of beta-amyloid in the etiology of Alzheimer's disease].
AB  - Amyloid beta-peptide (Abeta) is a key molecule in Alzheimer disease (AD).
      Cerebral deposition of Abeta was earlier thought to initiate the pathological
      cascade of AD, including the formation of senile plaques and neurofibrillary
      tangles, neuronal loss, and dementia. According to the classical amyloid
      hypothesis, the aggregation of Abeta into insoluble beta-sheet fibrils plays an
      important role in its neurotoxicity. However, this hypothesis is paradoxical: The
      concentrations of Abeta required for fibrillization and neurotoxicity are higher
      than its physiological concentrations. Cognitive decline in AD patients is not
      correlated with the levels of senile plaque formation or insoluble Abeta
      formation; instead it correlates with the levels of synapse loss and the levels
      of soluble Abeta. These observations suggest the existence of soluble toxic forms
      of Abeta in AD brains; these forms have recently been identified to be oligomeric
      assemblies of Abeta. At present, AD is believed to begin with synaptic
      dysfunction caused by soluble Abeta oligomers. This hypothesis termed the
      oligomer hypothesis, is based on the following observations: The levels of Abeta
      oligomers are high in AD brains. Exogenous Abeta oligomers at physiological
      concentrations cause synaptic and cognitive dysfunction in vivo and synapse loss
      and neuronal death in vitro. Furthermore, we observed that the E693delta mutation
      in the amyloid precursor protein found in AD patients causes disease by
      increasing the formation of Abeta oligomers without inducing the formation of
      Abeta fibrils or senile plaques. Currently, senile plaque formation is thought to
      occur in order to protect neurons from the toxicity of diffusible Abeta oligomers
      by sequestering them into deposits. Thus, soluble Abeta oligomers play a more
      important role in the etiology of AD insoluble Abeta fibrils.

PMID- 20675874
TI  - [Significance of tau in the development of Alzheimer's disease].
AB  - Based on the amyloid hypothesis, studies on for Alzheimer disease (AD) therapy
      mostly focus on elimination of beta-amyloid. However, results of recent studies
      on amyloid immunotherapy suggest that it may not be sufficient to target only
      beta-amyloid for AD therapy. Neurofibrillary tangles (NFTs), which contain
      hyperphosphorylated tau are the other pathological hallmark of AD; clinical
      progression of NFTs is from the entorhinal cortex to the limbic cortex, and
      neocortex. In a brain region showing NFTs, synapse loss and neuronal loss were
      observed; this suggests the possibility that NFT formation is involved in brain
      dysfunction because of synapse loss and neuronal loss. In the process of NFT
      formation, tau formed different aggregation species- tau oligomers, granules, and
      fibrils. From the analysis of different human tau-expressing mouse lines, soluble
      hyperphosphorylated tau, including the tau oligomer, was found to be involved in
      synapse loss; and granular tau formation was also found to be involved in
      neuronal loss. Therefore, inhibition of tau aggregation and tau phosphorylation
      is expected to prevent synapse loss and neuron loss, which may halt progressive
      dementia in AD.

PMID- 20675875
TI  - [Lifestyle-related diseases as risk factors for dementia].
AB  - In this article, we have reviewed the findings of prospective cohort studies
      throughout the world to examine influences of lifestyle-related diseases on the
      risks of total dementia, Alzheimer disease (AD), and vascular dementia (VD). In
      some cohort studies on elderly populations, diabetes was found to be consistently
      associated with the risk of VD, but was inconsistently associated with the risk
      of AD. A cohort study on the elderly residents of the town of Hisayama, Japan,
      revealed the significant associations between glucose intolerance and the risks
      of both VD and AD. Clinical and experimental evidence has indicated that glucose
      intolerance and diabetes induce dementia through various mechanisms such as
      atherosclerosis,microvascular disease, glucose toxicity, and impaired insulin
      metabolism. No cohort studies have indicated significant associations between
      late-life hypertension and the risk of AD, and only 1 study has revealed the
      significant influence of hypertension on the risk of VD in an elderly population.
      The Hisayama study revealed that late-life hypertension was a significant risk
      factor for the development of VD but not for AD. A few cohort studies have
      suggested the presence of significant associations between midlife hypertension
      and the risks of late-life AD and VD. Metabolic syndrome has been shown to be a
      risk factor for the development of cognitive impairment, but no prospective
      cohort studies have investigated the significant influence of this syndrome on
      the risk of AD or VD. Some cohort studies have examined the associations of
      hypercholesterolemia with the risk of AD, but the results were inconsistent.
      Further studies are required to resolve these issues.

PMID- 20675876
TI  - [Concept and clinical presentation of mild cognitive impairment].
AB  - Mild cognitive impairment (MCI) is considered to be a transition state between
      normal cognition and dementia. The subtype of MCI are highly heterogeneous in
      terms of etiology, presentation, and prognosis. Patients with the amnestic
      subtype of MCI are at a high risk of progression to Alzheimer disease (AD); this
      subtype may represent the prodromal stage of AD. In contrast, patients with the
      non-amnestic subtype may be at a high risk of progression to a non-AD dementia,
      including dementia with Lewy bodies, frontotemporal dementia, and vascular
      dementia. Most patients with amnestic MCI exhibit pathologic abnormalities in the
      mesial temporal lobe structures; several other concomitant pathologic
      abnormalities, including argyrophilic grain disease, neurofibrillary tangles,
      hippocampal sclerosis, and vascular lesions are also observed. Patients with MCI
      often exhibit neuropsychiatric symptoms, such as depression and apathy, and
      instrumental ADL are minimally restricted. Moreover, patients with MCI who are
      not aware of their memory deficits and in whom practice effects are not observed
      exhibit parietotemporal hypoperfusion on single photon emission CT, indicating
      that these findings are predictors of progression to AD. In this review, I have
      discussed the most current aspects related to the concept and clinical
      presentation of MCI, with emphasis possible risk factors for conversion to
      dementia.

PMID- 20675877
TI  - [Clinical characteristics of posterior cortical atrophy].
AB  - Posterior cortical atrophy (PCA) is a degenerative disease characterized by
      posterior cortical dysfunction, e. g. Balint syndrome and Gerstmann syndrome;
      however insight and memory are preserved. The most common neuropsychological
      symptoms seen in these patients are full blown Balint syndrome or some components
      of the syndrome. These patients behave differently from patients with stroke or
      traumatic injury. Patients with PCA manifesting as severe Balint syndrome, are
      almost blind except that they can walk without colliding with obstacles; in
      contrast patients with stroke or traumatic injury manifesting as Balint syndrome
      collide with obstacles. Although a number of studies have reported pathological
      backgrounds other than Alzheimer disease (AD) in patients with PCA. AD is the
      most common pathological background observed in such patients. The
      neuropsychological, morphological, and pathological profiles of patients with PCA
      differ from those of patients with typical AD. Recently, neuropsychological and
      pathological studies have reported cognitive diversity in patients with AD; PCA
      is a variant form of AD. Although the classification of PCAs into different
      categories might have little value with regard to pharmaceutical therapy, such
      information is important with regard to the care and support of patients with
      PCA.

PMID- 20675878
TI  - [Assessment scales for Alzheimer's disease].
AB  - Comprehensive examination is required to make an accurate and effective diagnosis
      of dementia associated with Alzheimer disease. Cognitive tests and psychological
      scales are useful for the objectively evaluation of symptoms that may not be
      completely revealed by the patient's medical history. The pattern and degree of
      the cognitive symptoms differ between individuals. The methods for evaluating the
      cognitive abilities of Alzheimer's patients can be divided into 2 categories. The
      first consists of cognitive tests that examine a certain aspect of cognitive
      function. The second consists of behavioral assessments that evaluate overall
      patient behavior. Cognitive tests specifically assess the domain of cognitive
      function, but their scope may be too narrow. Memory and visuospatial ability
      tests are useful and important for assessing Alzheimer patients. Behavioral
      assessments can evaluate the general condition of the patients, but there is a
      possibility of observer bias. Since Alzheimer disease has a prolonged course and
      is characterized by general changes, the concomitant use of cognitive tests and
      behavioral assessments is important for long-term assessment.

PMID- 20675879
TI  - [Neuroimaging for patients with Alzheimer disease in routine practice].
AB  - In routine practice neuroimaging has been applied as an adjunct technique for
      early and differential diagnosis of Alzheimer disease in routine practice. Of the
      several neuroimaging modalities, magnetic resonance imaging (MRI) and brain
      perfusion single-photon emission computed tomography (SPECT) have been commonly
      used in Japan; further software programs are used to aid statistical analysis of
      the imaging results. For example voxel-based specific regional analysis system
      for Alzheimer disease (VSRAD) for MRI and easy Z-score imaging system (eZIS) are
      used for the analysis of MRI and SPECT. In the early stage of Alzheimer disease,
      specific findings of regional atrophy and perfusion reduction are observed in
      some areas. In the posterior cingulate gyrus precuneus and parietal cortex,
      perfusion reduction was more frequently observed than atrophy. On the other hand,
      in the medial temporal structures, perfusion reduction was less frequently
      observed than atrophy. Perfusion reduction in the the posterior cingulate gyrus
      precuneus and in the parietal cortex was more prominent in the case of patients
      with early-onset Alzheimer disease than in the case of patients with late-onset
      Alzheimer disease. Further, atrophy in the medial temporal structures was more
      prominent in the case of patients with late-onset Alzheimer disease than in the
      case of those with early-onset Alzheimer disease. These findings are helpful for
      differentiating of Alzheimer disease from other diseases characterized by
      dementia.

PMID- 20675880
TI  - [Amyloid PET in Alzheimer research].
AB  - Amyloid positron emission tomography (PET) has recently emerged as a non-invasive
      neuroimaging technique for visualizing the accumulation of fibrillar amyloid-beta
      in the living human brain. Among several proposed radioligand tracers, Pittsburgh
      compound-B (PiB) has gained worldwide acceptance as a standard amyloid PET probe
      in a very short period because of its strong impact. Several lines of evidences
      from PiB-PET studies have suggested that the accumulation of amyloid-beta starts
      during the preclinical stage of Alzheimer disease (AD) and reaches the plateau
      phase before or during the mild cognitive impairment (MCI) stage. Therefore,
      amyloid-beta may be useful as a biomarker of AD, not only for the very early
      diagnosis but also for monitoring the therapeutic effect of disease-modifying
      agents that may reduce the amount of deposited amyloid-beta in the brains of
      patients with AD. Positive findings on amyloid PET along with amnestic MCI has
      been shown to be a strong predictor of AD conversion. The amyloid imaging
      technique is also useful to differentiate non-AD type degenerative disorders such
      as argyrophilic grain dementia and neurofibrillary tangle-dominant dementia,
      which are cumulatively called as tauopathies. Recently, many amyloid PET-positive
      and cognitively normal subjects were found in PiB-PET studies. PiB-PET studies on
      healthy subjects have also shown that apolipoprotein (APO) E4 boosts the
      accumulation of amyloid-beta and may consequently accelerate the pathogenesis of
      AD. In order to evaluate the clinical significance of positive and negative
      findings on amyloid PET, further prospective studies and comparison studies on
      PET pathology are essential.

PMID- 20675881
TI  - [Biological marker for Alzheimer's disease].
AB  - The possibility of that Alzheimer disease (AD)-modifying treatments such as
      amyloid beta-protein (Abeta) immunotherapies being available raises an urgent
      need for biological markers that will facilitate early and accurate diagnosis.
      This concept is now widely accepted,because without doubts that such treatments
      should be initiated during the early stages of the disease. In this review, we
      discusses the recent progress in identification of biological markers by placing
      a particular focus on Abeta and tau.

PMID- 20675882
TI  - [Drug therapy for Alzheimer's disease].
AB  - Cholinesterase inhibitors and memantine are widely used for the treatment of
      Alzheimer disease (AD) and other non-AD dementia worldwide. Since 2000, large
      scale prospective random control studies using meta-analysis have provided
      clinical evidence for the use of these drugs in AD and non-AD dementia. Here, we
      review these reports, including those on other drugs and newly developed drugs,
      which provide detailed clinical information for the daily management of dementia.

PMID- 20675883
TI  - [Development of new drugs for Alzheimer's disease].
AB  - Currently, only donepezil is available for the treatment of Alzheimer disease
      (AD) in Japan. Clinical trials of galantamine, rivastigmine, and memantine have
      been completed in Japan, and patients are awaiting government approval for the
      use of these drugs. The herbal medicine yokukansan was found to be effective for
      behavioral and psychological symptoms of dementia (BPSD) in patients, and
      juzentaihoto was found to reduce AD pathology in a mouse model. In addition,
      muscarinic and nicotinic acetylcholine receptor agonists, serotonergic agonists,
      other drugs are being developed. These medicines have little effect on the
      improvement of cognitive functions. The anti-histamine dimebolin was expected to
      have a significant effect on the improvement of cognitive functions, but
      unfortunately, it was rejected during phase III clinical trials. Disease
      modifying drugs such as alpha-secretase activators, beta- and gamma-secretase
      inhibitors or modulators, inhibitors of Abeta and tau aggregation, enhancers of
      Abeta degradation, immunotherapies to remove Abeta oligomers and fibrils, and
      neurotrophic factors are being developed. Some of these drugs are in phase III
      clinical trials and are expected to be available for clinical use in the near
      future.

PMID- 20675884
TI  - [Caring for patients with Alzheimer's disease].
AB  - The term "caring" refers to the process aimed at enabling people with
      disabilities to achieve and maintain optimal functioning. According to the
      International Classification of Functioning, Disability and Health (ICF) proposed
      by the World Health Organization in 2001, the functioning involves all aspects of
      daily life and applies to 3 levels: body functions and structures, activities,
      and participation. Caring is of 2 types; (1) therapeutic care, which restores and
      maintains the body functions; and (2) compensatory care, which compensates for
      the impairment of body functions and thus enhances and maintains the level of
      activity and participation. Alzheimer disease impairs multiple domains, including
      cognitive function and behaviors; therefore, it is very important to
      systematically and individually assess these impairments in each domain. Because
      there is inadequate data on the efficacy of cognitive training, compensatory care
      is principally used to overcome cognitive dysfunction. Caregivers should be
      equipped with skills required to cope with behavioral problems so that they can
      compensate for and even reduce these problems. Further, caregivers should not be
      overburdened, as this is reported to be a significant predictor for the poor
      outcome of patients with Alzheimer disease. Therefore, appropriate information
      regarding the disease, the impairments caused by it, the skills required to cope
      with these impairments, and social support services should be provided to the
      caregivers.

PMID- 20675885
TI  - [Thyroid-associated ophthalmopathy: case report of a euthyroid patient].

PMID- 20675886
TI  - 15th Conference of the European Society for Clinical Hemorheology and
      Microcirculation (ESCHM), June 28-July 1, 2009, Pontresina, Switzerland.

PMID- 20675887
TI  - Laudatio for the 2009 Fahraeus awardee: Prof. Dr. Friedrich Jung.

PMID- 20675888
TI  - From hemorheology to microcirculation and regenerative medicine: Fahraeus Lecture
      2009.

PMID- 20675889
TI  - Lessons from comparative hemorheology studies.
AB  - The flow properties of blood and its components vary widely throughout the animal
      kingdom. Even if nucleated avian and reptile red blood cells (RBC) are excluded
      from the analysis, RBC exhibit different rheological behavior among mammalian
      species. Both RBC aggregation and cellular deformability have been reported to
      vary among species, including placental mammals, marsupials, terrestrial and
      aquatic mammals. Although the relationships between blood flow behavior and
      species-specific characteristics have not been systematically investigated,
      studies to date allow recognition of interesting patterns, especially for RBC
      properties. These properties do not correlate with simple cellular parameters
      (e.g. mean cell volume), but more detailed analysis of RBC structure may reveal
      cellular aspects (e.g. surface charge density) that can be related to rheologic
      behavior. It has been postulated that the athletic capacity of mammalian species
      may predict the aggregation behavior of their RBC, but this hypothesis has not
      been supported by data from a wide range of athletic and sedentary species.
      Aquatic mammals also exhibit a very interesting diversity of hemorheological
      properties, which again are not yet easily related to specific circulatory
      adaptations. Data from current comparative studies suggest that a better
      understanding of the relations between specific hemorheological properties and
      specific hemodynamic adaptations in a variety of species should contribute to a
      better understanding of circulatory behavior; future studies are thus clearly
      indicated.

PMID- 20675890
TI  - Endothelial functions: Translating theory into clinical application.
AB  - The vascular endothelium plays a pivotal role in modulating endothelial
      homeostasis. A number of methods have been developed to assess the function of
      this important tissue in humans in vivo, in the hope that such data may
      contribute to the early diagnosis and risk stratification of patients at risk
      for, or with, cardiovascular disease. Despite these efforts, a number of issues,
      both practical and theoretical, arise from the attempt of quantifying the elusive
      "endothelial function", and from the attempt of defining what is "endothelial
      dysfunction". The present paper, based on a lecture held at the conference of the
      European Society of Hemorheology and Microcirculation, will try to deal with
      these issues.

PMID- 20675891
TI  - Degradation of and angiogenesis around multiblock copolymers containing poly(p
      dioxanone)- and poly(epsilon-caprolactone)-segments subcutaneously implanted in
      the rat neck.
AB  - The degradation behavior and the effect on angiogenesis of multiblock copolymers
      based on poly(p-dioxanone)- and poly(epsilon-caprolactone)-segments (PDC) were
      studied in vivo. PDC is a multifunctional biomaterial combining degradability and
      shape-memory capabilities. The "in vivo" degradation of PDC is characterized by a
      fragmentation occurring at the material tissue interface. This observation is
      consistent with the enzyme supported degradation behaviour, which was determined
      "in vitro". PDC revealed to induce the formation of blood micro-vessels nearby in
      the periimplantary tissues. Both might explain the good PDC integration into
      tissues in terms of a strong connection between the implant and the
      periimplantary tissue. Micro blood-vessels might be involved in the clearance of
      the small particles, which appear in the periimplantary tissue when PDC degrades.

PMID- 20675892
TI  - Reduced diagnostic value of lactate dehydrogenase (LDH) in the presence of
      radiographic contrast media.
AB  - Isoforms of the enzyme lactate dehydrogenase (LDH) were found in almost all cells
      of the organism and an elevated activity of LDH in the circulation is thought to
      be a clear indicator of elevated cell destruction coinciding with an increased
      release of components from the cellular cytoplasm, e.g. LDH. Here, we report on
      an in-vitro examination to test whether radiographic contrast media (RCM) could
      induce cell destruction followed by an increase in LDH release. The RCM were
      tested in non-flow cultures of human umbilical venous endothelial cells (HUVEC)
      of the fourth passage seeded on extracellular matrix and the results were
      compared to those from control cultures not exposed to contrast media. The
      examination revealed that the addition of contrast media to the cell culture
      media supplemented with pooled human serum (HSP) as source of exogenous LDH was
      followed by a strong decrease in LDH activity both in the absence and presence of
      HUVEC. Within 1.5 min after the addition of contrast media to the culture medium
      supplemented with HSP (30% vol of the culture medium were replaced by either of
      two contrast media, Iodixanol or Iopromide) the LDH activity decreased about 80%
      compared to the initial values. In contrast, the LDH activity did not change in
      cell culture media not supplemented with RCM. The partial replacement of HSP
      supplemented cell culture medium by RCM will cause a dilution of cell culture
      medium constituents. The decrease of LDH activity, however, was much stronger
      than the decrease thought to be attributable to the effects of dilution of cell
      culture medium, so that the role of dilution seems to be a minor one in this
      case. It has to be assumed that the RCM could interact with the LDH available in
      the culture medium as well as with the substrates delivered with the measurement
      system for the assessment of LDH activity, so that both, the amount of LDH and
      the activities of enzymes involved might be influenced. In the presence of HUVEC
      a similar effect was observed. Here, a little less strong decrease of LDH
      activity occurred compared to the decrease in cell culture medium without HUVEC.
      This was unexpected because a considerable amount of HUVEC were detached after
      the addition of contrast media and many of these cells were damaged seriously so
      that a significant amount of endogenous LDH should have been released. These
      unexpected results make it necessary to re-evaluate those past time examinations
      focussed on cell damage/destruction in the presence of contrast media, where the
      measurement of LDH activity was used as indicator or cell vitality and where cell
      decease rates were correlated to questionable toxic influences. According to the
      results of the examination reported here it is difficult to uphold the
      interpretation of recently published findings that contrast media almost
      exclusively induce cellular apoptosis and not necrosis.

PMID- 20675893
TI  - New fundamental and applied mechanisms in exercise hemorheology.
AB  - The present article summarizes recent data presented at the Exercise and
      Hemorheology symposium during the 15th Conference of the European Society for
      Clinical Hemorheology and Microcirculation (June 28-July 1, Pontresina,
      Switzerland, 2009). The review starts with several unresolved paradoxes in
      exercise hemorheology. Then, we focus on the potential hemorheological and
      immunological mechanisms involved in the adverse events sometimes reported in
      exercising sickle cell trait carriers, and the role of habitual physical
      activity. In a fourth part, new results on the effects of acute hypoxia on blood
      rheology are presented. Finally, we will discuss recent experimental evidences on
      the role of exercise on the regulation of nitric oxide synthesizing mechanisms in
      red blood cell.

PMID- 20675894
TI  - The different isoforms of the receptor for advanced glycation end products are
      modulated by pharmacological agents.
AB  - Elevated glucose concentration increases oxidation and Advanced Glycation End
      product (AGE) formation. The binding of circulatory AGEs or AGEs included in
      erythrocyte membrane to the receptor for AGEs (RAGE) generates in endothelial
      cells an oxidative stress and enhances the expression of inflammatory molecules.
      Engagement of RAGE by AGEs and subsequent signaling plays an important role in
      the development of diabetic complications. Soluble RAGE isoforms (sRAGE)
      neutralize the ligand-mediated damage by acting as a decoy. If the expression of
      RAGE is upregulated during the pathogenesis of inflammatory diseases, sRAGE
      mostly found decreased when complications ensue. By modulating RAGE isoform
      expression, it could be possible to reduce the incidence of complications. This
      review focused on the capability of Angiotensin Receptor Blockers (ARBs), which
      are used to treat patients with hypertension and/or diabetes, to modulate RAGE
      isoform expression because some data reported the interference with RAGE
      downstream. In this regard, three ARBs - irbesartan, telmisartan, candesartan
      cilexetil - were tested and provided evidence for their ability to inhibit in
      human endothelial cells the expression of membrane-bound and soluble RAGE
      isoforms induced by the inflammatory factor Tumor Necrosis Factor-alpha (TNF
      alpha), demonstrating the potential benefits of these molecules in RAGE-oriented
      therapies. Modulating RAGE isoforms expression by correcting endothelial
      dysfunction is achievable by drugs already used for hypertension or diabetes
      treatment such as ARBs.

PMID- 20675895
TI  - Evolution of rheological properties of erythrocytes and left ventricular geometry
      in cardiovascular disease risk patients.
AB  - The evolution of rheological properties of erythrocytes and geometrical
      parameters of left ventricle during therapies aimed at reducing cardiovascular
      disease (CVD) risk has been investigated. The study group consisted of 29
      individuals who were diagnosed with the presence of at least one CVD risk factor
      at the time of entry to the study. Appropriate therapies were applied and the
      patients were followed for two years. Two groups of patients could be
      distinguished. The first group consisted of 12 individuals who were rigorously
      applying the therapy and for whom blood pressure, total cholesterol, LDL and
      glucose returned to normal levels. The second group included 17 patients for whom
      the above mentioned parameters remained pathological in spite of the applied
      therapy. In the first group, erythrocyte deformability as well as LVMI improved:
      deformability increased on average by 17% (p < 0.025), whereas LVMI decreased by
      8% but not in a statistically significant manner (p < 0.27). In the second group,
      the results indicate worsening of both hemorheological properties and left
      ventricular geometry: RBC deformability became lower by 15% (p < 0.00001) and
      LVMI increased by 18% although this change was not statistically significant (p <
      0.19). The results indicate that blood rheology improves when the CVD risk is
      reduced by administered therapy and worsens when the risk increases. Similar
      behavior shows LVMI. It is very likely that left ventricular geometry is
      influenced by blood rheology.

PMID- 20675896
TI  - The endothelial-protective effects of HMG-CoA reductase inhibition in the setting
      of ischemia and reperfusion injury.
AB  - Animal studies have consistently demonstrated the ability of 3-hydroxy-3
      methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors to limit the damage
      induced by ischemia-reperfusion (IR) in the cardiac, cerebral and mesenteric
      circulation through a mechanism dependent on the upregulation of cyclooxygenase-2
      (COX-2). Our group performed studies aimed at investigating the mechanism of HMG
      CoA reductase inhibitor-mediated endothelial protection from IR injury, in
      particular the role of COX-2, in a human in vivo model of IR-induced endothelial
      dysfunction. We demonstrated that HMG-CoA reductase inhibition protects against
      IR-induced endothelial damage, an effect that was lost upon COX-2 inhibition.
      These observations may suggest a mechanistic explanation for the cardioprotection
      observed in clinical settings such as percutaneous coronary interventions and
      coronary artery bypass surgery and may also propose a mechanistic hypothesis for
      the reported cardiotoxic effects of cyclooxygenase-2 inhibitors observed in
      clinical studies. These studies are summarized and discussed in the present
      paper.

PMID- 20675897
TI  - Nitric oxide generation in red blood cells induced by mechanical stress.
AB  - Previous reports have demonstrated that red blood cells (RBC) have an active
      nitric oxide (NO) synthesizing mechanism which has properties similar to
      endothelial nitric oxide synthase (eNOS). This red cell NOS activity contributes
      to the NO export from RBC. The present study explored the influence of shear
      stress applied to RBC on NO concentrations of cell suspensions. RBC were exposed
      to shear stress by filtration through 5 microm diameter pores under 10 cm H2O
      pressure, generating a wall shear stress of approximately 110Pa. NO concentration
      in the RBC suspensions were measured using electrochemical NO probes before and
      after filtration through the micropores. NO concentration was found to be
      significantly increased after a single passage of RBC suspensions through the
      micropores. The increment in NO concentration depended on the presence of
      calcium, being 21.8+/-4.4 nM with 1 mM calcium and 13.7+/-2.7 nM without added
      calcium. Including the calcium chelator EDTA completely abolished this increase.
      The increment of NO was also affected by the level of oxygenation, being more
      pronounced under hypoxic conditions. These results confirm that RBC NO generating
      mechanisms can be stimulated by exposing red cells to shear stress and that
      calcium plays a role in this stimulation.

PMID- 20675898
TI  - Interaction effects of time of day and sub-maximal treadmill exercise on the main
      determinants of blood fluidity.
AB  - The purpose of this study was to investigate the effects of time of day on
      responses of the main determinants of blood rheology to acute endurance exercise.
      Ten healthy male subjects (age, 26.9 +/- 5.5 yr) performed two bouts of running
      at 65% of VO2peak for 45 min on a motorised treadmill in the morning (08:00 h)
      and evening (20:00 h), which were followed by 30 min recovery. The two exercise
      trials were performed in two separate days with 7 days intervening.
      Haemorheological variables were measured before, immediately after exercise and
      after recovery. Haematocrit, haemoglobin and RBC count were increased
      significantly (p < 0.01) after 45 min running in both morning and evening trials
      and normalised following recovery, irrespective of time of day. Plasma viscosity
      increased significantly (F2,18 = 12.4, p < 0.01) following sub-maximal exercise
      in both trials and returned to pre-exercise level at the end of recovery.
      Baseline values (p < 0.05) but not responses of plasma viscosity to exercise were
      significantly affected by time of day. Neither a significant main effect of
      exercise nor a significant (p > 0.05) time-of-day effect was found for plasma
      proteins. It was concluded that sub-maximal running at 08:00 or 20:00 h does not
      induce different responses in the main determinant of blood rheology.

PMID- 20675899
TI  - Ischemic and non-ischemic preconditioning: Endothelium-focused translation into
      clinical practice.
AB  - Pathophysiological studies have clearly demonstrated that the relationship
      between endothelial [dys]function and tissue ischemia is bidirectional: while it
      is well accepted that endothelial dysfunction has a key role in the progression
      and destabilization of coronary atherosclerosis, it is also well known that the
      endothelium is particularly sensitive to ischemia and reperfusion injury, and
      that this damage critically determines the extent of tissue damage, e.g.
      myocardial infarct size. Therefore, protecting the endothelium from ischemia
      could potentially have important clinical implications. In this scenario,
      reactive oxygen species [ROS] play a particularly important role: these elusive
      mediators are involved in determining the endothelial toxic effect of risk
      factors and are involved in reperfusion injury; however, most importantly, ROS
      are also key mediators of endothelial preconditioning, a protective process that
      is characterized by a reduced sensitivity to ischemia and reperfusion injury. We
      report considerations regarding these phenomena and their potential pharmacologic
      manipulation as discussed in a lecture at the recent Conference of the European
      Society of Clinical Hemorheology and Microcirculation held in Pontresina,
      Switzerland.

PMID- 20675900
TI  - Intraductally applied contrast-enhanced ultrasound (IA-CEUS) for improved
      visualization of obstructive diseases of the salivary glands, primary results.
AB  - PURPOSE: Obstructive diseases of the salivary glands are often based on
      Sialolithiasis; however, conventional radiological imaging or ultrasound does not
      provide a diagnosis in 5-10% of all cases. It was the aim of our study to examine
      the effectiveness and viability of an intraductal applied contrast-enhanced
      ultrasound (IA-CEUS) to improve the visualization of obstructive diseases of the
      salivary glands in comparison to conventional ultrasound and clinical symptoms.
      MATERIALS AND METHODS: The study included fifteen patients with swelling of
      indeterminate cause and/or pain of one or more salivary glands. A high-end
      ultrasound machine (Siemens, ACUSON, S 2000, Germany) with a multi-frequency
      linear 9 MHz transducer was used to carry out contrast-enhanced ultrasound with
      SonoVue. RESULTS: All patients were examined using all diagnostic ultrasound
      tools of the study. The results show that the procedure is easy and convenient to
      perform, as well as efficient, but more significantly, that the intraductal
      contrast agent improved the diagnostic assessment capabilities of ultrasound for
      patients with obstructive salivary gland diseases, thereby helping to identify
      the best treatment. CONCLUSION: In comparison to conventional ultrasound, the use
      of an intraductal applied contract-enhanced ultrasound not only improved the
      visualization of the glandular duct system as a whole, but was less time
      consuming as well as more reproducible. Thus, IA-CEUS with an intraductal applied
      contrast agent (IA-CEUS) is a promising tool that provides additional helpful
      information and an improvement for cases involving patients with unclear
      symptoms.

PMID- 20675901
TI  - Innovations in contrast enhanced high resolution ultrasound improve sonographic
      imaging of the intestine.
AB  - The aim was to describe the perfusion pattern of the inflamed bowel wall and the
      surrounding tissue in inflammatory bowel disease and diverticulitis of the
      sigmoid colon applying a high resolution matrix transducer and the new hybrid
      technique. We performed contrast enhanced ultrasound (CEUS) using an updated
      version of the 1-5 MHz (C1-5-D convex probe) and the 6-9 MHz probe (9L-D linear
      probe) as well as a matrix 6-15 MHz transducer (ML 6-15-D Matrix Array Linear
      Probe) and updated post-processing procedures to examine microvascularization of
      inflamed bowel wall in Crohn's disease (11 patients), ulcerative colitis (1
      patient) and diverticulitis of the sigmoid colon (2 patients). Assessment of
      mural microvascularization was successful as well as identification of fistulas
      (2 patients) and covered perforation (1 patient). Moreover analysis of time
      intensity curves revealed increase of signal intensity up to 20 dB. Summarizing,
      application of high resolution linear probes and use of updated post-processing
      methods substantially improve detection of inflammation-caused increased
      microcirculation of the bowel wall and the surrounding tissue as well as
      identification of complications as fistulas or covered perforations.

PMID- 20675902
TI  - Predictive value of duplex ultrasound for restenosis after renal artery stenting.
AB  - PURPOSE: Factors predicting renal function and recurrent stenosis following
      percutaneous renal revascularization are poorly identified. The predictive value
      of hemodynamic duplex ultrasound (DUS) parameters was evaluated. METHODS: In a
      prospective observational study patients undergoing stenting of renal artery
      stenosis (RAS) were included. Renal resistance index (RI) and peak systolic
      velocity (PSV) were measured at baseline, one day, and six months after
      intervention. RESULTS: At 6-months follow-up 16 (16.8%) restenosis of 105 treated
      renal arteries were detected. Baseline RI was 0.69 +/- 0.12 and increased
      significantly to 0.72 +/- 0.09 after 6 months (p < 0.0001), however, RI did not
      predict restenosis. PSV at baseline and age were independent predictors for
      increased RI at 6 months (p = 0.0078 and p = 0.0019). Diabetics had a significant
      higher RI before revascularization (0.74 +/- 0.08) than non-diabetics (0.68 +/-
      0.12, p = 0.04). PSV after stenting was higher in patients with restenosis (1.4
      +/- 0.4 m/sec vs. 1.0 +/- 0.3 m/sec, p = 0.002) and was an independent predictor
      for restenosis. CONCLUSIONS: Increased PSV within the stent one day after the
      procedure is predictive for restenosis. Patients with high grade RAS and older
      patients have a worse outcome. DUS is recommended to detect patients at risk for
      restenosis after percutaneous renal revascularization.

PMID- 20675903
TI  - Microcirculation of subepithelial gastric tumors using contrast-enhanced
      ultrasound.
AB  - OBJECTIVES: The evaluation of subepithelial tumors of the stomach is normally the
      domain of gastroscopy and endoscopic ultrasound. We investigated these rare
      tumors using transabdominal B-mode ultrasound and performed perfusion analysis of
      these tumors with contrast enhanced ultrasound. METHODS: Patients with
      gastrointestinal stromal tumors (GIST, n = 3), leiomyoma (n = 1) and schwannoma
      (n = 1) were routinely examined using conventional B-mode-ultrasound, colour
      Doppler ultrasound and contrast-enhanced ultrasound (contrast media: Sonovue;
      ultrasound device: Siemens Acuson Sequoia 512). Gastroscopy, endosonography with
      puncture of the subepithelial tumor and computed tomography were also performed
      in all patients. After surgery, the resected stomach tumors were correlated with
      the preoperative imaging findings. RESULTS: All calculated tumor sizes using any
      imaging modalities showed a good correlation with the macroscopic tumor sizes ex
      vivo. Histologically increased tumor size of the GISTs was correlated with large,
      central avascular areas. The GISTs and the leiomyoma presented with mixed
      echogenicity in B-mode-ultrasound. Colour Doppler ultrasound was able to detect
      some vessels in the periphery of the tumor only. Using contrast-enhanced
      ultrasound the GISTs and the leiomyoma presented hypervascular. The contrast
      pattern of these lesions was from the periphery to the centre or diffuse or a
      progressive centrifugal fill in during the arterial phase. We also registered
      slowly progressive washout starting at the end of the arterial phase and
      increasing into the late phase. The contrast media behaviour in the schwannoma
      was different from that describt above within the GISTs: it was noted to have a
      diffuse intralesional pattern at the start of the arterial phase followed by an
      early, rapidly progressing washout-phenomenon. CONCLUSION: In our pilot study B
      mode transabdominal ultrasound was able to visualise gastric subepithelial tumors
      larger than three centimetre. Contrast-enhanced ultrasound is a proven method in
      clinical practice for the perfusion analysis of gastric subepithelial tumors. It
      can also be used for the planning of ultrasound-guided biopsies to avoid
      punctures of necrotic tumor parts.

PMID- 20675904
TI  - Common carotid artery hemodynamic factors in patients with cerebral infarctions.
AB  - The aim of the study was to investigate the changes of the common carotid local
      hemodynamic factors like wall shear stress and tensile forces in 16 patients with
      chronic unilateral cerebral infarctions (CUCI), 58 patients with risk factors
      (RF) for cerebrovascular disease (CVD) and 25 healthy control subjects. The blood
      flow velocities (BFV), the internal diameters (D) and the vessel wall intima
      media thickness (IMT) in the common carotid arteries (CCA) were recorded with
      color duplex sonography. Systolic (SBP) and diastolic (DBP) blood pressure were
      measured and mean blood pressure (MBP) was calculated by the formula of Wiggers.
      Whole blood viscosity (WBV) at the shear rate of 94.5 s-1 was measured on the day
      of the Doppler ultrasound examination with a rotational viscometer Contraves Low
      Shear 30. Wall shear stress (WSS), the circumferential wall tension (T) and the
      tensile stress tau were calculated. The main RF in the patients' groups were
      hypertension and hyperlipidemia. The SBP, WBV and IMT were significantly
      increased in the patients with UCI and RF for CVD in comparison to controls.
      Lower systolic WSS and tau and higher T were established in the patients with
      UCI. The IMT correlated with WSS and tau. The study confirms the complex
      influence of the changes in WBV and blood pressure for the development of carotid
      atherosclerosis.

PMID- 20675905
TI  - Influence of hemorheological parameters and mean blood pressure on carotid blood
      flow asymmetry in patients with chronic unilateral cerebral infarctions.
AB  - The study aimed to follow the influence of some hemorheological parameters and
      mean blood pressure (MBP) on the carotid blood flow asymmetry in 20 patients with
      chronic unilateral cerebral infarctions (UCI) as compared to 30 patients with
      transient ischemic attacks (TIAs), 17 patients with risk factors (RF) for
      cerebrovascular disease (CVD) and 11 healthy controls. Hemorheological variables:
      hematocrit (HT), plasma (PV) and whole blood viscosity (WBV), serum lipids and
      echocardiographic parameters were investigated. Blood pressure (systolic,
      diastolic and mean) was registered and color duplex sonography of the carotid
      arteries was performed. The lumen diameter, the intima media thickness (IMT) and
      the blood flow velocity (systolic, mean and diastolic) in the carotid arteries
      were examined and the velocity asymmetry ratio (AR) was calculated. Significant
      increase of HT in UCI, of mean blood pressure (MBP) in the patients with RF and
      TIAs and of IMT and velocity parameters in all patients was established. The
      correlation analysis revealed parallel influence of HT, MBP, cardiac function,
      IMT, lumen diameter and some of the modifiable RF on the carotid AR in patients
      with chronic UCI affecting mainly the collateral circulation. The complex
      investigation of these factors would enable us to individualize the therapeutic
      approach in the patients with cerebral ischemic events.

PMID- 20675906
TI  - Platelet morphological, functional and rheological properties attributable to
      addictions.
AB  - Hemorheological abnormalities such as elevated whole blood viscosity, plasma
      viscosity, erythrocyte deformability and platelet aggregation, hematocrit and
      fibrinogen levels, are frequently examined as diagnostic tool and prognostic
      relevance in socially important hemorheological disorders. Distinct biological -
      morphological and functional platelet alterations, have been described in
      different addictions (heroin-, cocaine-, nicotine-, alcohol-, etc.). Chronic
      addictions could cause biochemical and conformational changes in platelets and
      their membranes, thus modulating platelet receptor expression, morphology
      (anisocytosis, giant platelets) and activation (alpha-granule release), platelet
      aggregation and hemorheological properties. Some of these alterations in chronic
      addicts - documented at cellular- and molecular level, could be easily used as a
      precise diagnostic tool with regard to thromboembolic complications and
      microcirulation injuries attributable to addictions. The present review focuses
      on some changes in platelet morphological, functional and rheological properties
      induced by chronic opiate/opioid abuse. Hypothesis is accumulated that free fatty
      acids (FFAs) and especially oleic acid (OA) could cause positive molecular and
      conformational changes in platelets of addicts with hemorheological disorders.

PMID- 20675907
TI  - Experimental evaluation of mechanical and electrical properties of RBC
      suspensions under flow. Role of RBC aggregating agent.
AB  - Mechanical and electrical properties of red blood cells (RBC) suspensions in
      dextran 70 (Dx70), dextran 150 (Dx150), dextran 500 (Dx500) and
      polyethileneglycol (PEG) 35,000 with different concentrations were evaluated
      through apparent viscosity and conductivity measurements under steady and
      unsteady flow conditions. RBCs suspensions of the washed RBS in PBS (control) and
      Dx70, Dx150, Dx500 and PEG in PBS with different concentrations, adjusted to the
      same hematocrit of 40% were used for the experiments. Conductivity time and shear
      rate dependences in parallel with the rheological properties of the samples were
      studied under transient flow regimes at different local structure of the uniform
      Couette flow. Their relationships on dextrans and PEG concentrations were
      evaluated too. Low shear viscosity increased and conductivity decreased of RBC
      suspensions, compared to non-aggregating suspensions, depending on dextrans and
      PEG concentrations. A time course of blood conductivity recorded under different
      flow conditions provides experimental description of RBC aggregation
      disaggregation processes and other cell-cell interactions. The results show that
      the blood conductivity is strongly dependent on the considered blood factors and
      is influenced by flow, shear rates and concentration of dextran and PEG
      solutions.

PMID- 20675908
TI  - Gender differences of blood rheological parameters in laboratory animals.
AB  - Although growing number of evidences supports the gender differences of
      hemorheological variables in human, little is known about this question in
      experimental animals. Investigating this question and giving laboratory-specific
      reference values, blood samples from healthy male and female CD rats and beagle
      dogs were tested for hematological parameters (microcell counter), blood and
      plasma viscosity (capillary viscometer), erythrocyte deformability (bulk
      filtrometry and ektacytometry), erythrocyte aggregation (light transmission
      aggregometer) and fibrinogen concentration (coagulometer). Besides the inter
      species alterations we found hematological gender differences too regarding the
      red blood cell count and hematocrit. In rats the erythrocyte aggregation index
      was higher in females, while in beagle dogs the males showed significantly higher
      aggregation index values. In rats the red blood cell deformability showed better
      values in females. In beagle dogs this was the opposite, the males had better
      elongation index (EI) values in the function of shear stress (SS). Besides this
      it was also experienced that the shape of the canine EI - SS curves differed from
      the rats' values. Gender differences with inter-species alterations can be
      observed in laboratory animals (rats and dogs) that have to be taken under
      consideration during planning experiments and evaluating results.

PMID- 20675909
TI  - Examination of aggregation of various red blood cell populations can be
      informative in comparison of splenectomy and spleen autotransplantation in animal
      experiments.
AB  - Using "Furka's spleen-chip" autotransplantation technique, in a follow-up study
      we investigated erythrocyte aggregation and its influencing factors regarding to
      asplenic-hyposplenic conditions. Healthy beagle dogs were equally divided into 4
      groups: "Sham"- sham operated control, "SE"-splenectomy, "AU-5" and "AU-10"
      autotransplantation with 5 or 10 spleen chips by Furka-method after splenectomy.
      Blood sampling for current investigation occurred on the 12th, 18th, 20th and
      24th postoperative months, besides comprehensive structural and functional
      examinations. In this study we focused on the aggregation properties of
      erythrocytes in native samples and of density separated "young" versus "old"
      erythrocytes (Myrenne MA-1 aggregometer). Fibrinogen concentration (Sysmex CA-500
      coagulometer) and erythrocyte sedimentation rate (ESR) were also determined. SE
      group showed significantly elevated ratio of "old" and "young" erythrocyte
      aggregation index values on the 20th and 24th postoperative months (1.5 and 2.16,
      respectively) comparing to the AU (1.14 and 1.05) and Sham groups (1.2 and 1.27).
      In SE group fibrinogen concentration was mildly higher and ESR almost doubled
      versus control. The greater differences experienced between "young" and "old"
      erythrocytes may reflect decreased splenic filtration function. Consequently, the
      comparison of aggregation and deformability properties of "young" and "old"
      erythrocytes may give important information about the function of the spleen.

PMID- 20675910
TI  - Splenic function and red blood cell deformability: The beneficial effects of
      spleen autotransplantation in animal experiments.
AB  - Erythrocyte deformability could be a suitable parameter reflecting hyposplenic
      asplenic conditions after splenectomy or spleen autotransplantation. The aim of
      this study was to analyze the efficacy of spleen autotransplantation using
      filtrometry and ektacytometry for testing erythrocyte deformability, besides
      complex structural, functional, hematological, hemostaseological and
      immunological examinations. Healthy beagle dogs were subjected to the study in
      the following experimental groups: "Sham"-sham operated control, "SE"
      splenectomy, "AU-5" and "AU-10"-autotransplantation with 5 or 10 spleen chips
      using "Furka's spleen chip" technique after splenectomy. Blood samples were taken
      before the operations and monthly afterwards for 1 year and bi-monthly till the
      end of the 2nd postoperative year. Erythrocyte deformability was measured by bulk
      filtrometry (relative cell transit time, RCTT) and on the 20th-24th postoperative
      months by ektacytometry (elongation index, EI), too. RCTT was elevated in
      operated groups till the 12th month. On the 20th/24th months "SE"-group expressed
      the highest level, while the "AU"-groups were close to "Sham"-group. Using
      ektacytometer we found that on the 20th/24th month both EImax and SS1/2 showed
      the lowest values (because of unusual curve characteristic) in "SE"-group and
      "AU"-groups almost reached the "SH"-group. Spleen autotransplantation partially
      restored the normal rheological conditions. Both filtrometry and ektacytometry
      was suitable to investigate hyposplenic-asplenic conditions.

PMID- 20675911
TI  - Application of leukocyte antisedimentation rate calculation in investigation of
      spleen salvaging experimental surgical techniques.
AB  - Clinical studied showed leukocyte antisedimentation rate (LAR) changes in various
      conditions that modulate the immune system. There is a lack of LAR data in animal
      experiments concerning splenic function after splenectomy or spleen preserving
      operations, thus we aimed to include LAR in our ongoing inbred canine study on
      following-up spleen salvaging surgical techniques. Blood samples of healthy
      beagle dogs served as normal control. The experimental groups were: "SH"-sham
      operated, "SE"-splenectomy, "R1/3" and "R2/3"-one-third/two-third of the spleen
      resected, "AU-5" and "AU-10"-autotransplantation with 5/10 spleen chips using
      Furka's techniques. On the 12th postoperative month Rabigen-Mono+Vanguard-Plus-5
      vaccines were given to the animals, which provoked immune response. Blood samples
      were taken before and one week after the vaccination. LAR was calculated by
      Bogar's method. In normal control group LAR was 3.11, leukocyte count was 12.04
      G/l. In the experimental groups LAR varied between 2.4-7.3 before vaccination.
      After vaccination LAR increased in all groups. Although "SE" group expressed the
      largest changes (LAR = 16.56; 135%), the leukocyte count increased only by 12%.
      In "AU" groups the increase was smaller, while "R" groups showed slight changes
      only. LAR can be applicable in animal experiments and may serve as a
      supplementary parameter in hemorheological investigations of hyposplenic-asplenic
      states.

PMID- 20675912
TI  - Fibrinolytic and procoagulant activity in septic and haemorrhagic shock.
AB  - Septic and haemorhagic shock carry the risk of high mortality. Failure of
      microcirculation secondary to alterations of haemostasis and fibrinolysis play a
      major role in the pathogenesis of shock. The aim of this study was to evaluate
      the clinical relevance of procoagulatory and fibrinolytic activities referring to
      survival. Therefore, 39 patients (23 to 80 yrs, 16 females, 23 males) suffering
      from haemorrhagic (n = 21) and septic shock (n = 18) were screened prospectively
      for plasmatic coagulation and fibrinolysis parameters. Thirteen patients (33.3%)
      developed lethal outcome. Concerning fibrinolysis, plasminogen was significantly
      lower in non-survivors by day 1 and plasmin-antiplasmin complex significantly
      higher by day 4 compared to survivors. Consecutive increase of plasminogen over
      day 4 and 7 was significantly stronger in survivors. Concerning haemostasis
      activation, thrombin-antithrombin complex was higher and D-dimers or fibrinogen
      levels were lower, but not significantly different, in non-survivors compared to
      survivors. We conclude from these data, that procoagulant activities are
      increased, but not significantly predictive for the clinical outcome in septic
      and haemorrhagic shock. By contrast, fibrinolysis, as measured by enhanced
      capacity and responsiveness, is clearly predictive and plays a significant role
      for survival, possibly due to its clearing function in microcirculation.

PMID- 20675913
TI  - Effects of phosphodiesterase (III/IV)-inhibitors and cytokines on mechanical
      properties of neutrophilic granulocytes in neonates and adults.
AB  - Sequestration of activated PMN and enrichment in tissues play a key role in
      tissue damage during septicaemia and after ischemia/reperfusion. Since
      polymorphonuclear neutrophilic granulocytes (PMN) of term neonates show various
      functional differences compared to PMN in adults (decreased chemotaxis, decreased
      intracellular killing, decreased adhesion) we studied the influence of
      interleukin 8 (IL-8), tumor necrosis factor-alpha (TNF-alpha) and N-formyl
      methionyl-leucyl-phenylalanine (fMLP) on the reduction of deformability of PMN in
      neonates and adults. The following phosphodiesterase (PDE)-inhibitors were
      applied to ameliorate the reduction in deformability when the PMN were stimulated
      with fMLP or IL-8: Enoximone, Milrinone (PDE-III-inhibitors), Pentoxifylline
      (PTX) and Piclamilast (PDE-IV-inhibitors). The micropipette technique and the
      cell transit analyzer (CTA) were used and compared. Aspiration times into
      micropipettes with an internal diameter of 5 microm, transit times through 8
      microm filter pores and neutrophil elastase concentrations were determined.
      Despite of the functional differences of PMN in neonates compared to adults the
      significant decrease of deformability of PMN activated with cytokines compared to
      passive PMN was not different in both groups. The neutrophil elastase
      concentrations reflect the activation of the PMN: highest concentrations during
      activation, decreased concentrations due to PDE-inhibitors, and PMN in a passive
      state. The neutrophil elastase concentrations were not different from PMN of
      neonates and adults. These PDE-inhibitors significantly increased the
      deformability of activated PMN but significant differences between the
      deformability of PMN in neonates and adults were not found. Despite the
      functional differences of PMN in neonates PDE-III/IV-inhibitors lead to similar
      improvement of mechanical properties of activated PMN in neonates and adults.
      These drugs may ameliorate impaired microcirculation also in neonates during
      inflammation.

PMID- 20675914
TI  - Rheological and hemostasiological aspects of thrombus formation in the left
      atrial appendage in atrial fibrillation? A new strategy for prevention of
      cardioembolic stroke.
AB  - Atrial fibrillation (AF), as the most common cardiac rhythm disturbance, gains in
      importance not only for the persons affected, but also for health care and social
      economy due to thromboembolic events, of which stroke is the most serious,
      disabling, and life threatening one. Cardiac embolism is due to thrombus
      formation mainly in the left atrial appendage (LAA). The pathophysiology leading
      to increased thrombogenicity is complex and requires a remodelling of the LAA
      structure, decreased LAA blood flow, activation of inflammatory processes,
      deviations of the hemostatic/fibrinolytic system, and activation/dysfunction of
      endothelial/endocardial cells. Altogether, a prothrombotic state proposed by
      Virchow more than 150 years ago. The presence of a LAA thrombus, therefore, is a
      result of a dynamic process of clot formation and lysis. A comprehensive
      understanding of this pathophysiology is helpful to optimize the management of
      patients at high risk of cardioembolic stroke. Especially those with
      contraindications for oral anticoagulation are in a need of an alternative
      approach that is not associated with a long-term risk of hemorrhage and other
      attendant circumstances. The reasonable alternative may be the exclusion of the
      LAA cavity from circulation by either surgical or percutaneous catheter-based
      procedures.

PMID- 20675915
TI  - The impact of rosiglitazone on nitric oxide bioavailability and endothelial
      function.
AB  - Clinical studies have demonstrated that rosiglitazone can improve vascular
      function in patients with diabetes mellitus. It remains unclear whether this
      effect depends on a direct improvement in endothelial function or whether it is
      mediated by the drug's effect on glycemic control. Yet, rosiglitazone has been
      linked to serious cardiovascular events. A number of studies recently
      investigated whether rosiglitazone affects endothelial function in healthy
      volunteers and patients with cardiovascular disease. Controversial observations
      have been reported; the observation that rosiglitazone might in certain cases
      impair endothelial function may suggest a mechanistic explanation for the
      observation of increased cardiovascular events in patients treated with
      rosiglitazone who have underlying cardiovascular disease. These studies are
      summarized and discussed in the present paper.

PMID- 20675916
TI  - The effects of colorectally insufflated oxygen-ozone on red blood cell rheology
      in rabbits.
AB  - Currently, with reappraisal of ozone therapy, it has been utilized worldwide in
      research and clinical field. Most of the studies investigating effects of ozone
      on blood parameters are conducted by directly ozonating the blood. Rectal
      insufflation is a simple, easy and inexpensive method of delivering ozone. Little
      is known how these gases affect some fundamental hemorheologic parameters when
      given by insufflation. We aimed to investigate the effects of colorectally
      insufflated oxygen-ozone on red blood cell rheology in rabbits. Rabbits were
      divided into Group 1 (control); Groups 2, 3 and 4 (oxygen rectally insufflated
      respectively for 15, 21 and 36 days); Groups 5, 6 and 7 (ozone rectally
      insufflated respectively for 15, 21 and 36 days). Erythrocyte deformability,
      aggregation and osmotic fragility were determined from blood samples at the end
      of each treatment period. Our study showed an improvement in deformability, a
      decrease in aggregation and an increase in fragility following a 15 day ozone
      treatment. With longer ozone application the changes in aggregation and fragility
      returned back to control levels, however its effect on deformability sustained.
      Therefore, more than two weeks ozone insufflation may induce adaptation to
      changes induced by ozone suggesting its systemic effects.

PMID- 20675917
TI  - Crosstalk between adenylyl cyclase signaling pathway and Ca2+ regulatory
      mechanism under red blood cell microrheological changes.
AB  - There are evidences that red blood cell (RBC) deformation and aggregation change
      under their incubation with catecholamines and it is connected with activation of
      intracellular signaling pathways. The present study was designed to explore the
      adenylyl cyclase signaling pathway and Ca2+ regulatory mechanism of RBCs together
      with their microrheological changes. The washed RBCs were resuspended in PBS. In
      each of the three research sessions RBC suspensions were divided into two
      aliquots: 1) control (without drug) and 2) with an appropriate drug. After cell
      incubation RBC deformability (RBCD) and aggregation (RBCA) were estimated. RBC
      incubation with catecholamines resulted in RBCD changes by 18-30%. RBCs
      incubation with forskolin facilitated an increase of RBCD by 17% (p < 0.05). A
      significant deformability rise under dB-AMP incubation was found by 27% (p <
      0.01). Ca2+ cell influx, stimulated by A23187, was accompanied by an increase of
      RBCA; whereas red cell deformability was changed only slightly. On the other
      hand, Ca2+ entry blocking into the cells by verapamil has led to significant RBCA
      decrease and RBCD rise. The obtained results make us believe that RBCD change was
      closely associated with Ca2+ control mechanisms. An effect of Ca2+ concentration
      increase on RBC microrheology was removed, if it was preliminary added to
      incubation medium EGTA as Ca2+ chelator. It was found that all four PDE
      inhibitors: IBMX, vinpocetine, rolipram, pentoxifylline decreased RBCA
      significantly and, quite the contrary, they increased red cell deformability. Our
      data have shown that Ca2+ entry increase was accompanied by red cell aggregation
      rise, while adenylyl cyclase-cAMP system stimulation led to red cell
      deformability increase and its aggregation lowered. The crosstalk between two
      intracellular signaling systems is probably connected with phosphodiesterase
      activity.

PMID- 20675918
TI  - In vitro evaluation of a nitinol based vein cuff for external valvuloplasty.
AB  - This study shows first in vitro tests of a nitinol based vein cuff developed for
      external valvuloplasty. In contrary to currently existing vein cuffs the tested
      model enables minimal invasive implantation and also maintains its round pre
      shaped profile at body temperature (37 degrees C). The examination of the cuff
      surface structure by scanning electron microscopy, profilometry and X-ray
      photoelectron spectroscopy after sterilization with ethylene oxide and before
      cyto-compatibility testing revealed a nearly smooth surface (mean square
      roughness Rq 66 +/- 33 nm) which was primarily composed of nickel, oxygen,
      titanium, carbon and silicon where nickel was the least fraction (Ni: 0.7%, Ti:
      1.7%, Si: 15.8%, O: 29.5%, C: 52.3%) of the surface elements. Si and C are
      supposed to be contaminations caused by a final cuff polishing with silicon
      carbide at the end of the manufacturing process. To evaluate cyto-compatibility
      initial cell adherence and cell activity were assessed. The results showed good
      initial cell adherence of L929 fibroblast-like cells on the cuff surface already
      after 24 h. The results also revealed no inhibitory effects on the activity of
      these cells (MTS test) later on. The test setup developed to analyse
      functionality in a dynamic mode was shown to be suited at blood pressures up to
      300 mmHg. The cuff successfully limited dilation of varicose veins (Vena saphena
      magna) at physiological blood pressures (< 120 mmHg) and also in cases of
      hypertonia (300 mmHg) to the diameter determined by the cuff (4.0 mm) over
      thecomplete testing period. This indicates that the clasp based cuff closure
      mechanism is suited to close the cuff under variable physiological and
      pathological blood pressure conditions. The cuff structure only allowed minimal
      adaptation on the inhomogenously dilating vein profile in the both peripheral
      cuff modules. Both peripheral modules followed the vessel dilation in correlation
      to the applied pressure. At pressures within the physiological range </= 120
      mmHg) the variation of the lateral arch module diameter was only marginal,
      whereas at 300 mmHg pressure the peripheral modules followed vein dilation up to
      a diameter of 5.0 to 5.5 mm. The cuff also maintained the pre-shaped round
      profile in the central and peripheral modules during the pressure increase and
      the consecutive cuff expansion. The study showed that the first nitinol based
      vein cuff for external valvuloplasty was processed well enough by
      electropolishing and sterilization to allow culturing of L929 fibroblast-like
      cells on the cuff surface as a test of general biocompatibility. The cuff also
      proved to limit dilation of varicose veins at physiological and pathological
      blood pressures in vitro. Further tests with primary cells from the venous wall
      will follow to test the specific biocompatibility before tests in vivo can be
      envisaged.

PMID- 20675919
TI  - Acute effects of short-term exposure to second-hand smoke on induced platelet
      aggregation.
AB  - Passive smoking may increase cardiovascular events by yet insufficiently
      understood mechanisms. We, therefore, tested the hypothesis that passive smoking
      could affect platelet aggregation. Fourteen healthy non-smoking males were
      exposed to second-hand smoke during 60 min in a room with smokers, who maintained
      the CO-concentration between 4.5-7.0 ppm throughout that period. Citrated blood
      was drawn before and immediately after smoke exposure (which took place between 6
      and 7 p.m.). The last 7 individuals had blood taken also at 9.00 a.m. before and
      the day after smoke exposure. Platelet aggregation was measured (a) in flowing
      whole blood using the platelet function analyser PFA-100, which determines the
      closure time (CT) of a collagen coated membrane pore by shear-induced platelet
      aggregation, and (b) with a Chrono-log 700 Aggregometer, assessing platelet
      aggregation either by the change of impedance in diluted whole blood or light
      transmission in platelet-rich plasma. After short term second-hand smoke exposure
      we did not observe an increase in platelet aggregation with any of the
      instruments. We conclude that acute exposure to second-hand smoke is unlikely to
      increase platelet aggregability. Other mechanisms must be involved in the
      increased risk of cardiovascular events associated with passive smoking.

PMID- 20675920
TI  - Regular physical activity alters the postocclusive reactive hyperemia of the
      cutaneous microcirculation.
AB  - Regular physical activity leads to increased endothelium-dependent
      vasodilatation. Postocclusive reactive hyperemia (PRH) is a transient increase of
      blood flow after the release of an arterial occlusion and has been used as a
      clinical tool to estimate endothelial function. The aim of our study was to
      assess the potential effect of regular physical training on PRH of skin
      microcirculation. Skin blood flux was estimated by laser-Doppler fluxmetry (LDF)
      in two groups of subjects: 12 highly trained athletes and 12 age-matched
      sedentary controls. LDF was measured on two specific skin sites: volar aspect of
      the forearm (nonglabrous area) and finger pulp of the middle finger (glabrous
      area). After the release of a 3-min occlusion of the brachial artery, we
      determined the following indices of PRH: the time to peak (tpeak), the maximal
      LDF (LDFpeak), the recovery time (trec), the area under the PRH curve (AUC).
      Baseline LDF did not differ between the trained and sedentary subjects in either
      site. On the forearm, we found no significant differences in either PRH
      parameter. On the contrary, on the finger pulp, there were statistically
      significant differences in the tpeak and the AUC (p < or = 0.05). The results
      show an altered PRH response of skin microcirculation in the finger pulp in the
      trained subjects. We may speculate that this could be the result of an increased
      endothelial vasodilator capacity. Further, the potential adaptations of the
      endothelium differ between the glabrous and nonglabrous skin sites.

PMID- 20675921
TI  - The influence of erythrocyte aggregation on induced platelet aggregation.
AB  - Red blood cells (RBCs) affect platelet aggregation in flowing blood (primary
      hemostasis). We tested the hypothesis that RBC aggregation could influence
      platelet aggregation. RBC aggregation was altered in vitro by: (i) changing
      plasma aggregatory properties with 3.7 g% dextran 40 (D40), 3.0 g% dextran 70
      (D70) or 1.55 g% dextran 500 (D500); (ii) changing RBC aggregatory properties by
      incubating RBCs in 50 mU/ml neuraminidase for 60 min (reduction of the surface
      sialic acid content, thus reducing electrostatic repulsion) and subsequent RBC
      resuspension in platelet rich plasma (PRP) containing 1 g% dextran 70. RBC
      aggregation was assessed with the sedimentation rate (ESR). Platelet aggregation
      was measured: (i) in flowing whole blood with a platelet function analyzer PFA
      100(R), which simulates in vivo conditions with RBCs flowing in the center and
      platelets along the wall, where they adhere to collagen and aggregate; and (ii)
      in a Chrono-log 700 Aggregometer, which measures changes of impedance by platelet
      aggregation in whole blood or changes in light transmission in PRP. We found that
      RBC aggregation increased with increasing molecular weight of dextran (ESR: 4 +/-
      3 mm/h, 34 +/- 14 mm/h and 89 +/- 23 mm/hfor D40, D70 and D500, respectively, p <
      0.0001) and with neuraminidase-treated RBCs (76 +/- 27 mm/h vs 27 +/- 8 mm/h,
      respectively, p < 0.0001). Platelet aggregation measured in whole blood under
      flow conditions (PFA-100) and without flow (Chronolog Aggregometer) was not
      affected by RBC aggregation. Our data suggest that RBC aggregation does not
      affect platelet aggregation in vitro and plays no role in primary hemostasis.

PMID- 20675922
TI  - Overhead rotation: A simple method to assess the mechanical stability of stored
      erythrocytes.
AB  - Erythrocytes loose some functional qualities during storage, which may influence
      the outcome after transfusion. One of them is mechanical stability, which
      determines their in vivo survival in the circulation. We have analyzed different
      forms of mechanical stress and have developed a simple, reproducible test for
      mechanical stability. Specimens of outdated erythrocyte units stored under
      routine conditions were investigated. Mechanical stress was applied either by
      rolling blood-containing 5 ml tubes at 15 rpm (Mixer 820, Swelab, Sweden) or
      overhead rotation at 10 rpm (Intelli-Mixer RM-2S Elmi, Skyline, Axon Lab AG,
      Baden, Switzerland). Free hemoglobin (Hb) in the supernatant was used as a
      parameter of membrane integrity. Stored erythrocyte units at the end of their
      "shelf-life" of 42 days had a median free Hb concentration of 1.8 g/l (25-75
      percentiles: 1.8-2.6 g/l) corresponding to a spontaneous hemolysis rate of 0.31%
      (0.28-0.46%). In samples subjected to 24 h rolling, free Hb rose to 4.8 (4.0-7.0;
      p = 0.005). Overhead rotation for 24 h increased free Hb to 17.1 (12.2-27.9) g/l
      when 1.5 ml blood in 5 ml tubes were used, and to 38.0 (19.6-55.2) g/l when 4.5
      ml in 5 ml tubes were used (p = 0.005 between the two groups), indicating that
      hemolysis during rotation depended on the blood volume. The type of tube also
      influenced the extent of hemolysis. A large variation was seen between different
      RBC units. The time course of hemolysis was an inverse exponential function; i.e.
      2 h of rotation induced already 45% and 7 h 86% of the hemolysis measured after a
      24 h rotation. We conclude that the rate of hemolysis after a standardized
      overhead rotation is a simple, useful laboratory test to determine the mechanical
      stability of stored erythrocytes. Large variations between different RBC units
      suggest that this may be valuable tool for the quality control of stored RBCs.

PMID- 20675923
TI  - Effects of time of day and acute resistance exercise on platelet activation and
      function.
AB  - The present study was designed to ascertain the interaction between time of day
      and resistance exercise on platelet activation and function. Ten healthy male
      subjects (age, 29.3 +/- 4.5 yr) undertook identical bouts of resistance exercise
      on two separate occasions. Tests were randomised and performed at two different
      time of day (08:00 and 20:00 h). Subjects performed 3 sets of 7 repetitions of
      six exercises at 80% of 1RM, which was followed by 30 min recovery. Beta
      thromboglobulin (B-TG) and platelet indices were measured at rest, post-exercise
      and at the completion of recovery. Platelet aggregation was determined in
      platelet rich plasma using collagen and three different concentrations of
      adenosine-5'-diphosphate. Platelet aggregations induced by different aggregating
      agents at rest were significantly higher in the morning (p < 0.05). Although
      platelet aggregations induced by collagen and ADP did not change in response to
      resistance exercise, significant differences between the results in the morning
      and evening trials were observed (p < 0.01). These differences emulated the
      differences observed at rest. A significant (P < 0.05) increase in B-TG was found
      following exercise with no difference between morning and evening trials. It was
      concluded that resistance exercise induces significant changes in platelet
      activation, irrespective of time of day, as assessed by beta-thromboglobulin.

PMID- 20675924
TI  - Melt-processable hydrophobic acrylonitrile-based copolymer systems with
      adjustable elastic properties designed for biomedical applications.
AB  - Acrylonitrile-based polymer systems (PAN) are comprehensively explored as
      versatile biomaterials having various potential biomedical applications, such as
      membranes for extra corporal devices or matrixes for guided skin reconstruction.
      The surface properties (e.g. hydrophilicity or charges) of such materials can be
      tailored over a wide range by variation of molecular parameters such as different
      co-monomers or their sequence structure. Some of these materials show interesting
      biofunctionalities such as capability for selective cell cultivation. So far, the
      majority of AN-based copolymers, which were investigated in physiological
      environments, were processed from the solution (e.g. membranes), as these
      materials are thermo-sensitive and might degrade when heated. In this work we
      aimed at the synthesis of hydrophobic, melt-processable AN-based copolymers with
      adjustable elastic properties for preparation of model scaffolds with controlled
      pore geometry and size. For this purpose a series of copolymers from
      acrylonitrile and n-butyl acrylate (nBA) was synthesized via free radical
      copolymerisation technique. The content of nBA in the copolymer varied from 45
      wt% to 70 wt%, which was confirmed by 1H-NMR spectroscopy. The glass transition
      temperatures (Tg) of the P(AN-co-nBA) copolymers determined by differential
      scanning calorimetry (DSC) decreased from 58 degrees C to 20 degrees C with
      increasing nBA-content, which was in excellent agreement with the prediction of
      the Gordon-Taylor equation based on the Tgs of the homopolymers. The Young's
      modulus obtained in tensile tests was found to decrease significantly with rising
      nBA-content from 1062 MPa to 1.2 MPa. All copolymers could be successfully
      processed from the melt with processing temperatures ranging from 50 degrees C to
      170 degrees C, whereby thermally induced decomposition was only observed at
      temperatures higher than 320 degrees C in thermal gravimetric analysis (TGA).
      Finally, the melt processed P(AN-co-nBA) biomaterials were sterilized with
      ethylene oxide and tested for cytotoxicity in direct contact tests with L929
      cells according to the EN DIN ISO standard 10993-5. All tested samples exhibited
      non-toxic effects on the functional integrity of the cell membrane and the
      mitochondrial activity. However, the morphology of the cells on the samples was
      different from that observed on polystyrene as control, indicating slightly
      cytotoxic effects according to the evaluation guide of the US Pharmacopeial
      Convention. Thus, the melt-processable, hydrophobic P(AN-co-nBA) copolymers with
      adjustable mechanical properties are promising candidates for in vitro
      investigations of tissue growth kinetics.

PMID- 20675925
TI  - [Genetic basis for skeletal disease. Nosology and molecular classification of
      skeletal dysplasias].
AB  - Skeletal dysplasias are a phenotypically and genetically heterogeneous group of
      disorders. Recent versions of the "nosology and classification of genetic
      skeletal disorders" have been based on the concept that disorders with similar
      clinical and radiographic abnormalities would have similar molecular bases.
      However, growing genetic/molecular evidence indicates that this is not
      necessarily the case. On the other hand, a molecular-pathogenic approach would be
      more appropriate to understand the pathophysiology behind these diseases and to
      facilitate research. Future revisions would need to integrate these two different
      strategies.

PMID- 20675926
TI  - [Genetic basis for skeletal disease. Genetic factors of osteoarthritis with
      particular reference to skeletal dysplasia].
AB  - Osteoarthritis (OA) is a degenerative disease of articular cartilage.
      Etiologically, it is classified as primary (idiopathic) and secondary forms.
      Primary OA is a polygenic disease based on genetic and environmental factors.
      Identification of its genetic factor, i.e., the susceptibility genes is rapidly
      in progress. Skeletal dysplasia, inherent failure of formation and/or development
      of the skeleton, is the frequent cause of secondary OA. Many diseases that belong
      to skeletal dysplasia, in particular, those which have epiphyseal dysplasia
      frequently associate OA. Recently, identification of disease genes for skeletal
      dysplasias is also rapidly in progress. In this paper, I review recent advance in
      the study of OA susceptibility genes with focus on the relation to disease genes
      for skeletal dysplasia.

PMID- 20675927
TI  - [Genetic basis for skeletal disease. Radiological approach for genetic skeletal
      disorders].
AB  - Genetic skeletal disorders comprise two broad categories, including bone
      dysplasia and dysostosis. Bone dysplasia refers to disorders in which the entire
      skeleton is more or less affected, while dysostosis to disorders in which
      individual bones are affected singly or in combination. The former occurs as a
      result of impaired genes (proteins) that play a pivotal role in both
      organogenesis and maintenance of bone and cartilage, while the latter as a result
      of impaired genes (proteins) that are important only in the organogenesis. In
      this review, the author focuses on radiological signs and their pathogenic
      mechanism commonly seen in bone dysplasias. However, it is important to realize
      that a radiological diagnosis of bone dysplasias depends on an overall pattern of
      skeletal abnormalities rather than single radiological signs, alone or in
      combination.

PMID- 20675928
TI  - [Genetic basis for skeletal disease. Genetic defects in chondrodysplasia].
AB  - Chondrodysplasia is a subset of skeletal dysplasia caused by genetic defects
      affecting chondrogenesis and its development, showing abnormal shape and
      structure of the skeleton. Pathology of growth plate results in defective
      skeletal development, such as short stature, while pathology of articular
      cartilage predisposes degenerative skeletal disease, such as early-onset
      osteoarthritis. Recently identified genetic basis for chondrodysplasia
      contributed much in understanding the biology and pathology of cartilage. The
      accumulated knowledge would be a clue to develop fundamental treatment for
      chondrodysplasia.

PMID- 20675929
TI  - [Genetic basis for skeletal disease. Osteogenesis imperfecta and genetic
      abnormalities].
AB  - Patients with osteogenesis imperfecta (OI) represent various degrees of bone
      fragility and accompany many clinical manifestations such as dentinogenesis
      imperfecta, blue sclera, growth disturbance, hearing impairment and so on.
      Although most OI is caused by genetic mutation of type I collagen gene ; COL1A1
      and COL1A2, other genes that concerns post-translational modification of type I
      collagen molecules such as CRTAP, LEPRE1, PPIB, SERPINH1 and FKBP10 were found to
      be the causative candidates of OI. On the other hand, genetic causes of type V
      and type VI OI are not identified. For the classification of OI, Sillence's
      classification had been used and had been repeatedly revised at the times of
      identification of new causative genes of OI.

PMID- 20675930
TI  - [Genetic basis for skeletal disease. Molecular advances in sclerosing bone
      disorders].
AB  - Sclerosing bone disorders are caused by impaired osteoclastic bone resorption or
      increased bone formation. Osteopetrosis, a representative disease caused by
      impaired bone resorption, is a heterogeneous disease, and various molecules have
      been recently identified to be responsible. In infantile malignant osteopetrosis,
      there are osteoclast-rich and osteoclast-poor forms, which are caused by
      dysfunction of osteoclasts and impaired osteoclastogenesis, respectively. As to
      the sclerosing bone diseases related to the increased bone formation, molecular
      analyses of these disorders uncovered the involvement of TGF-beta and Wnt
      signaling in the regulation of bone mass.

PMID- 20675931
TI  - [Genetic basis for skeletal disease. Establishment of novel treatments for
      fibrodysplasia ossificans progressiva (FOP)].
AB  - Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disorder
      characterized by progressive heterotopic bone formation in skeletal muscle
      tissue. In patients with FOP, heterozygous mutations have been identified in the
      BMP type I receptor, ALK2. This finding stimulates establishment of some animal
      models of FOP and development of novel treatments for FOP.

PMID- 20675932
TI  - [Genetic basis for skeletal disease. CNP therapy for achondroplasia].
AB  - By using transgenic and knockout mice, we have elucidated that C-type natriuretic
      peptide (CNP) is a potent stimulator of endochondral bone growth. Furthermore,
      loss-of-function mutations in the gene coding for guanylyl cyclase-B (GC-B) , the
      specific receptor for CNP, have been proved to cause impaired skeletal growth in
      humans. Following these results, we have started to translate the stimulatory
      effect of CNP on endochondral bone growth into the therapy for patients with
      achondroplasia, and have shown that targeted overexpression of CNP in cartilage
      or systemic administration of CNP reverses the impaired skeletal growth of mice
      model of achondroplasia.

PMID- 20675933
TI  - [Genetic basis for skeletal disease. Clinical characteristics of hypophosphatasia
      and its treatment].
AB  - Hypophosphatsia is caused by the defect of tissue-nonspecific alkaline
      phosphatase (ALP), and exhibits hypomineralization of skeleton and rachitic
      change of bone. The most severe form of hypophosphatasia is a perinatal form,
      which is also called a lethal form. However, some patients of this form can
      survive due to advances in neonatology. Other forms consist of infantile,
      childhood, adult and odonto types. Conventional therapies for hypophosphatasia
      are administration of vitamin B6 for convulsion and low calcium-containing milk
      for hypercalcemia. Bone marrow transplantation has been reported to treat several
      patients with hypophosphatasia. However, the method must be developed which
      improves the survival of donor mesenchymal cells in patients. Recombinant bone
      targeted ALP therapy is now on clinical trial in Canada and U.S.A and expected to
      be available in near future.

PMID- 20675934
TI  - [Genetic basis for skeletal disease. Stem cell therapy for genetic bone
      disorders].
AB  - Mesenchymal stem cells (MSCs) can show osteogenic differentiation capability when
      implanted in vivo , as well as cultured in vitro; therefore we attempted to use
      allogeneic MSCs for a patient with hypophosphatasia, which is caused by mutations
      in tissue non-specific alkaline phosphatase (TNSALP) gene. Donor MSCs were
      obtained by culture expansion of fresh marrow from the patient's father. Some of
      the MSCs were further cultured under osteogenic conditions on a culture dish or
      porous hydroxyapatite ceramics, resulting in cultured osteoblasts and osteogenic
      constructs, respectively. After traditional bone marrow transplantation, The
      donor MSCs and osteoblasts were injected into the patient and the constructs were
      implanted subcutaneously or intraosseous lesions. The patient's respiratory
      condition improved and donor cells were detected in newly formed bone tissue.
      These findings showed the importance of allogeneic MSC transplantation for the
      hypophosphatasia patient.

PMID- 20675935
TI  - [Genetic basis for skeletal disease. Hereditary rickets].
AB  - Hereditary rickets is caused by inborn error of vitamin D activation, vitamin D
      receptor (VDR) function or increased urinary phosphate excretion. Loss-of
      function mutation of 1alpha-hydroxylase gene and loss-of-function mutation of VDR
      gene result in vitamin D-dependent rickets type I and type II, respectively. X
      linked hypophosphatemic rickets (XLH) is the most common type of hypophosphatemic
      rickets, and autosomal dominant (ADHR) and negative (ARHR) types are rare. The
      diagnosis may be sometimes difficult and increasing cases of vitamin D deficiency
      must be distinguished.

PMID- 20675936
TI  - [Genetic basis for skeletal disease. Osteogenesis imperfecta].
AB  - Osteogenesis imperfecta (OI) is characterized by its bone fragility. But the
      spectrum of the severity of the fragility is widely distributed. Recently, amino
      bisphosphonate has been introduced into the treatment of the bone fragility of
      OI. Apparently, the treatment may reduce the frequency of the fractures in severe
      form of OI. However, its efficacy has not been supported by strong evidences,
      such as randomized controlled clinical trial. This section describes the
      pathophysiology and new pathogenetic mechanism of OI, and describes recent
      evidence for the efficacy of BP treatment in OI.

PMID- 20675937
TI  - [Genetic basis for skeletal disease. Orthopaedic intervention for bone
      dysplasias].
AB  - The aims of orthopaedic intervention for bone dysplasias are to maintain joint
      function, to prevent neurological complications, and then to improve the
      patient's quality of life. Bone lengthening technique can not only increase the
      body height, but also correct malalignment of the limb at the same treatment
      session, which is important to prevent early occurrence of the degenerative
      osteoarthritis. Intramedullary nailing for osteogenesis imperfecta protects long
      bones from fractures and prevents malunion when fracture takes place. Spinal
      instrumentation surgery is effective for prevention of the neurological
      complications and deterioration of the spinal deformities.

PMID- 20675938
TI  - [Genetic basis for skeletal disease. Dental management of patients with bone
      diseases].
AB  - Malformation of teeth can be found in patients with bone diseases, which was
      induced when the disease occurred during the tooth formation. The tooth
      malformation shows typical manifestations of the disease, which may demonstrate
      the occurrence of the bone disease. In this article, dental management of the
      patients with bone diseases such as X-linked hypophosphatemic rickets,
      osteogenesis imperfecta, and hypophosphatasia was presented.

PMID- 20675939
TI  - Introduction. The 10th anniversary of the establishment of the Tuskegee
      University National Center for Bioethics in Research and Health Care.

PMID- 20675940
TI  - Unsung hero: Monroe Nathan Work (theologian, social scientist, and crusader for
      social justice and civil rights).

PMID- 20675941
TI  - Sankofan socio-ethical reflections: the Tuskegee University National Bioethics
      Center's decade of operation, 1999-2009.
AB  - Primarily, this is a Sankofan socio-ethical analysis of the moral foundation of
      the Tuskegee University National Bioethics Center's decade of operation. The
      first section of the study will do the following: a) a Sankofan socio-ethical
      analysis of the Center's raison d'etre; and b) definitions of ethical terms and
      the social world of the infamous syphilis study. The second section, as a result
      of the analysis, will address the Center's following challenges: c) the Center's
      challenge of theory and practice; d) the Center's challenge of moral heritage;
      and e) the Center's challenge of the future.

PMID- 20675942
TI  - Tuskegee Bioethics Center 10th anniversary presentation: "Commemorating 10 years:
      ethical perspectives on origin and destiny".
AB  - More than 70 years have passed since the beginning of the Public Health Service
      syphilis study in Tuskegee, Alabama, and it has been over a decade since
      President Bill Clinton formally apologized for it and held a ceremony for the
      Tuskegee study participants. The official launching of the Tuskegee University
      National Center for Bioethics in Research and Health Care took place two years
      after President Clinton's apology. How might we fittingly discuss the Center's
      10th Anniversary and the topic 'Commemorating 10 Years: Ethical Perspectives on
      Origin and Destiny'? Over a decade ago, a series of writers, many of them African
      Americans, wrote a text entitled 'African-American Perspectives on Biomedical
      Ethics'; their text was partly responsible for a prolonged reflection by others
      to produce a subsequent work, 'African American Bioethics: Culture, Race and
      Identity'. What is the relationship between the discipline of bioethics and
      African American culture? This and related questions are explored in this
      commentary.

PMID- 20675943
TI  - Invoking "Tuskegee": problems in health disparities, genetic assumptions, and
      history.
AB  - Since 1972 the word "Tuskegee" has functioned as a metaphor for racism,
      paternalism, and deadly deception in government-sponsored medical research. There
      remain new lessons to be considered. We must understand how concepts of race
      become spoken and written about and then embedded in science that has racist
      implications. We have to consider how the researchers in the Tuskegee syphilis
      study assumed that syphilis was almost a different disease in Blacks and Whites,
      and yet were eager to make race disappear as the study's results would be used to
      generalize the concern for the dangers of syphilis. If we only look at what
      happened in that study as the past, or learn from it in narrow ways, we are in
      danger of re-creating the thinking that made it possible in the first place.

PMID- 20675944
TI  - The ethics of good communication in a complex research partnership.
AB  - The tripartite partnership among Morehouse School of Medicine, Tuskegee
      University, and University of Alabama at Birmingham is complex. In 2005, the
      three schools--with different institutional cultures, characters, and resources-
      agreed to collaborate in efforts to eliminate racial/ethnic disparities in cancer
      burdens. Pursuing this laudable aim predictably involved some miscommunication.
      The Bioethics Shared Resource (BSR) group foresaw such challenges and monitored
      interactions to prevent harm, noting that while effective communication is
      critical to the achievement of mutual goals, an understanding and prudent use of
      proven communication principles is a sine qua non for success. In this
      commentary, we share the undergirding moral concepts, communication approaches,
      and lessons learned. This experience has led us to propose an ethics of good
      communication for others to consider.

PMID- 20675945
TI  - A foundation for public health ethics at Tuskegee University in the 21st century.
AB  - This commentary is a reflection on Tuskegee University's National Center for
      Bioethics in Research and Health Care on the health and ethical challenges of the
      21st century. The Center has dedicated the last 10 years to addressing the
      unresolved biomedicine and public health issues and/or the ethical dilemmas that
      plague the nation's health. The authors believe that health disparities continue
      to worsen because the approach under-appreciates the ethical dilemma that plagues
      health policy and health disparities. The authors discuss synergies and the
      paradigmatic differences between science and medicine, religion, spirituality,
      and faith. They also discuss the importance of considering these relationships if
      improvements in the health of people of African descent are expected. The concept
      of Optimal Health is explored.

PMID- 20675946
TI  - Dietary consumption practices and cancer risk in African Americans in the rural
      South.
AB  - This study describes the dietary consumption practices of a sample of African
      Americans in the rural South. A qualitative research design involving a cross
      sectional food diary was utilized. Complete datasets were collected from 114
      participants, 66% female, between the ages of 19 and 79 years. The consumption of
      a variety of fruits, non-starchy vegetables and unprocessed cereals in daily
      meals was low in this sample. Frequent consumption of fried foods; fast foods;
      sugary, carbonated beverages; processed, high-fat and high-sodium foods; and low
      fruit and non-starchy vegetable intake were evident. The findings are crucial to
      the development for culturally-specific nutrition education intervention programs
      for African Americans in the rural South targeted at the modification of not only
      diet, but food preparation methods to reduce cancer risk.

PMID- 20675947
TI  - A comparison of two educational methods on immigrant Latinas breast cancer
      knowledge and screening behaviors.
AB  - Underutilization of screening mammography by Latinas continues unabated and may
      contribute to disparities in disease-free survival and mortality. OBJECTIVE:
      Comparison of two discussion group-centered educational interventions at
      enhancing breast cancer knowledge, breast self-exams (BSE), and screening
      mammography. METHODS: Pre-test post-test study design. Two cohorts of 200 Latinas
      each participated in survey screening and discussion groups at baseline. One
      cohort also viewed an animated video and had BSE training. Breast cancer
      knowledge, self-reported BSE and mammography history were measured at baseline
      and three months post-intervention. RESULTS: Breast cancer knowledge scores were
      good for both groups at baseline, and significantly increased at three month
      follow-up for both groups (p<.05) but no significant difference was observed
      between groups at baseline or post-intervention. CONCLUSION: Community-based
      discussion groups are a cost-effective method for improving breast cancer
      knowledge and promoting screening behaviors.

PMID- 20675948
TI  - Increasing prostate cancer screening among African American men.
AB  - The study evaluates the impact of prostate cancer education on screening rates
      among African American men in rural Black Belt counties in Alabama. The goal of
      the study is to promote screening behavior in African American men. The
      objectives were: 1) to identify enablers and barriers to screening; 2) to develop
      and test the effectiveness of an education intervention; and 3) to determine the
      impact of the intervention on prostate cancer screening rates through follow-up
      survey. The study followed a quasi-experimental three-phase design: 1) focus
      group, 2) education intervention, and 3) follow-up. Focus groups (N = 76)
      indicate men are reluctant to talk about their health with anyone. Analysis of
      pre-test and post-test paired t-test indicate a significant increase in knowledge
      and awareness of prostate cancer (85%). Follow-up survey results indicate that
      48% (N = 105) of the participants who had not been screened within the last 12
      months were screened after attending the education session.

PMID- 20675949
TI  - Healthy Lifestyle: a community-based cancer awareness and prevention intervention
      program.
AB  - Healthy Lifestyle engages the community in the development of a health behavior
      modification program to reduce cancer risk among African Americans. The
      objectives are 1) to assess knowledge, attitudes, and behaviors that affect
      cancer risk through focus group discussions; and 2) to identify community members
      to implement programs and practices that facilitate healthy behavior routines.
      Thirty-four African American focus group participants completed surveys regarding
      health knowledge and behavioral practices. Results from the focus groups
      identified three themes: 1) Health and Nutrition; 2) Environment; and 3) Family.
      The majority of focus group participants (94%) indicated that annual physical
      exams were important. However, of that group, 47% had not had a physical within
      the last 12 months and only 44% had scheduled appointments. Of the 79% who
      indicated they could commit to a two-year study, only 64% felt they could be
      leaders.

PMID- 20675950
TI  - Familias Sanas: an intervention designed to increase rates of postpartum visits
      among Latinas.
AB  - Familias Sanas (Healthy Families) is an educational intervention implemented and
      tested with low-income, immigrant Latina mothers. The program was designed to
      reduce existing health disadvantages of Latinas by empowering them to take active
      part in the management of their health and by encouraging them to advocate for
      themselves. Familias Sanas was implemented at a prenatal clinic located at a
      major urban hospital in the southwestern U.S. The efficacy of the intervention
      was evaluated through a randomized control trial measuring the participants' rate
      of postpartum visits and other relevant well-being measures. Initial findings
      show a significant effect of the intervention, with participants in the
      experimental group returning for their postpartum clinic visit at a higher rate
      in comparison with the control group. The results are discussed from a culturally
      specific perspective. Practice, policy, and research implications and
      recommendations are provided.

PMID- 20675951
TI  - Culturally targeted educational intervention to increase colorectal health
      awareness among African Americans.
AB  - BACKGROUND/OBJECTIVES: Colorectal cancer (CRC) is the third cause of cancer
      deaths for African Americans. OBJECTIVES: 1) increase CRC knowledge, 2) decrease
      cancer fatalism, and 3) increase colonoscopy screening for CRC among African
      Americans in North Carolina. METHODS: Churches and community-based organizations
      were randomized into intervention and control groups. The intervention group
      received a 90-minute culturally targeted educational program on colorectal
      health. Pre-test and post-test questionnaires were completed by both groups.
      RESULTS: A total of 539 African American men and women 50 years of age and older
      participated in this study. The intervention group had a significantly greater
      proportion of those receiving a colonoscopy within three months after the
      educational session than the control group. In the intervention group, CRC
      knowledge significantly increased and cancer fatalism attitudes significantly
      decreased. CONCLUSIONS: A culturally targeted faith/community-based educational
      intervention can increase CRC knowledge, decrease cancer fatalism, and increase
      screening for CRC among African Americans.

PMID- 20675952
TI  - Increasing HIV-related knowledge, communication, and testing intentions among
      Latinos: Protege tu Familia: Hazte la Prueba.
AB  - Latinos are less likely to be aware of their HIV seropositivity than African
      Americans and Whites. 'Protege tu Familia: Hazte la Prueba' is a culturally and
      linguistically-sensitive HIV/AIDS prevention and testing program targeting Latino
      families. Using community-based participatory research techniques, Spanish
      speaking bicultural community health workers helped develop and then used an
      educational flip chart and materials to conduct outreach and HIV prevention
      education in diverse settings. The intervention was created to increase HIV/AIDS
      related knowledge, to improve communication regarding sexual risk, and to augment
      intentions to use condoms and test for HIV. A secondary purpose was to decrease
      HIV-related stigma by improving knowledge about transmission and reducing
      homophobia. Participants demonstrated significant increases in HIV knowledge,
      intention to practice safer sex and communicate sexual risk to partner(s), and
      intention to test for HIV. Improvements were also found in self-reported comfort
      levels when interacting with and caring for the HIV positive, thus decreasing
      HIV/AIDS-related stigma.

PMID- 20675953
TI  - Promoting diabetes self-management among African Americans: an educational
      intervention.
AB  - Diabetes is a major national health problem that affects African Americans more
      seriously than other population groups. The purpose of this project was to
      increase knowledge and self-management of diabetes among African American adults
      40 years of age and older diagnosed with type II diabetes. A quasi-experimental
      pre-test/post-test comparison group design was used. Three educational sessions
      were provided to participants in the intervention group. Content included
      information about diabetes and its complications, risk factors, proper diet,
      recommendations for exercise, medications, and monitoring blood glucose. Teaching
      strategies included discussion, games, and demonstrations. Patient navigators
      provided follow-up by phone at the scheduled intervals. Preliminary results
      indicated significantly increased knowledge among intervention group participants
      between the pre- and post-test and the pre-test and follow-up. Findings for HbA1c
      values, body mass index, and weight were not significant.

PMID- 20675954
TI  - Comparative adaptation accuracy of acrylic denture bases evaluated by two
      different methods.
AB  - This study examined the adaptation accuracy of acrylic denture base processed
      using fluid-resin (PERform), injection-moldings (SR-Ivocap, Success, Mak Press),
      and two compression-molding techniques. The adaptation accuracy was measured
      primarily by the posterior border gaps at the mid-palatal area using a microscope
      and subsequently by weighing of the weight of the impression material between the
      denture base and master cast using hand-mixed and automixed silicone. The
      correlation between the data measured using these two test methods was examined.
      The PERform and Mak Press produced significantly smaller maximum palatal gap
      dimensions than the other groups (p<0.05). Mak Press also showed a significantly
      smaller weight of automixed silicone material than the other groups (p<0.05),
      while SR-Ivocap and Success showed similar adaptation accuracy to the compression
      molding denture. The correlationship between the magnitude of the posterior
      border gap and the weight of the silicone impression materials was affected by
      either the material or mixing variables.

PMID- 20675956
TI  - New approaches to blockade of the renin-angiotensin-aldosterone system: evidence
      from randomized controlled trials (RCTs) of angiotensin-converting enzyme
      inhibitors and angiotensin II-receptor blockers--questions remain unsolved.
AB  - Recent randomized controlled trials showed that blockade of the renin-angiotensin
      system (RAS) by angiotensin-converting enzyme (ACE) inhibitors and angiotensin II
      receptor blockers (ARBs) reduced cardiovascular and renal events. These drugs are
      widely used in the management of cardiovascular and renal diseases. Results from
      Randomized Controlled Trials (RCTs) so far, however, also raise several questions
      to be addressed. It should be noted that the residual event rate in the treatment
      arm in outcome studies that have employed ACE inhibitors or ARBs remains high.
      Such insufficient efficacy of RAS inhibition may result from the fact that
      neither ACE inhibitors nor ARBs completely suppress activity of RAS. Since then
      effort has been made to determine whether the dual blockade of RAS could provide
      further improvement in cardiovascular and renal outcome. This review extracts
      unsolved questions in the treatment with RAS inhibitors from outcome studies and
      discusses them from the clinical pharmacological point of view.

PMID- 20675955
TI  - More intensive lipid lowering is associated with regression of coronary
      atherosclerosis in diabetic patients with acute coronary syndrome--sub-analysis
      of JAPAN-ACS study.
AB  - AIM: We have shown that aggressive lipid lowering by pitavastatin and
      atorvastatin results in marked regression of atherosclerotic coronary lesions
      after acute coronary syndrome (ACS). The purpose of this study was to address the
      association of lipid levels after statin therapy with regression of
      atherosclerotic coronary lesions and major cardiovascular events in patients
      after ACS. METHODS: JAPAN-ACS is a prospective, randomized open-label study
      performed at 33 centers in Japan. Patients with ACS undergoing intravascular
      ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) were randomly
      assigned to receive either 4 mg/day pitavastatin or 20 mg/day atorvastatin within
      72 hours after PCI. IVUS image was obtained in 251 patients, including 73
      diabetic patients. Lipid profiles at the end of the study were divided into
      quartiles and the association with the percent change in non-culprit coronary
      plaque volume (PV) was assessed in total and diabetic patients. We also studied
      whether baseline and follow-up levels of HDL-cholesterol are associated with
      restenosis after PCI. RESULTS: Decreasing LDL-cholesterol, non-HDL-cholesterol,
      LDL-C/HDL-C ratio, apolipoprotein B quartiles were associated with a
      progressively smaller plaque burden in total and diabetic patients. In diabetic
      patients, further reduction of these parameters was associated with a
      significantly greater reduction in PV. We also found that patients with lower HDL
      cholesterol had a significantly higher incidence of target lesion
      revascularization. CONCLUSIONS: Early intensive statin therapy in patients after
      ACS results in remarkable regression of coronary PV. Diabetic patients can have a
      benefit with more intensive therapy to achieve a lower target level in Japanese.

PMID- 20675957
TI  - New approaches to blockade of the renin-angiotensin-aldosterone system:
      mineralocorticoid-receptor blockers exert antihypertensive and renoprotective
      effects independently of the renin-angiotensin system.
AB  - The role of angiotensin II in mediating hypertension and renal diseases is well
      documented, and inhibition of the renin-angiotensin-aldosterone system elicits
      antihypertensive and renoprotective effects. There is increasing evidence
      implicating aldosterone, in addition to angiotensin II, in the pathogenesis of
      hypertension and renal diseases. Beneficial effects of mineralocorticoid receptor
      (MR) blockers against these diseases have been reported and are independent of
      the effects exerted by renin-angiotensin system (RAS) inhibitors. MR blockers are
      increasingly being used, not only for primary aldosteronism but also for other
      resistant hypertensive patients whose blood pressure is insufficiently controlled
      by RAS inhibitors. In these settings, MR blockers have shown impressive results.
      In addition, anti-proteinuric effects of MR blockers have been observed in
      hypertensive patients treated with RAS inhibitors, but without significant
      effects on blood pressure. Interestingly, these effects of MR blockers are not
      always dependent on plasma aldosterone levels. These data suggest that MR
      blockers provide a potential therapeutic approach for patients with hypertension
      and renal impairment who are being treated with RAS inhibitors.

PMID- 20675958
TI  - New approaches to blockade of the renin-angiotensin-aldosterone system: chymase
      as an important target to prevent organ damage.
AB  - Chymase plays a crucial role in angiotensin II formation in various tissues.
      Angiotensin II induces gene expression of transforming growth factor (TGF)-beta
      and matrix metalloproteinase (MMP)-9 precursors, and chymase can convert
      precursors of TGF-beta and MMP-9 to their active forms. In cultured fibroblasts,
      significant increases in cell growth and TGF-beta levels were observed after
      chymase injection; these increases were inhibited by a chymase inhibitor, but not
      by an angiotensin II-receptor blocker. In apolipoprotein E-deficient mice,
      abdominal aortic aneurysm (AAA) development depends on an increase in MMP-9
      activities induced by angiotensin II infusion, but the inhibition of MMP-9
      activation by a chymase inhibitor resulted in attenuation of the angiotensin II
      induced AAA development. The upregulation of MMP-9 and TGF-beta levels is
      involved in damage to various organs, but these gene expressions are not
      completely induced by angiotensin II alone. Therefore, chymase inhibition may be
      useful for attenuating MMP-9 and TGF-beta levels, in addition to reducing
      angiotensin II formation, and this function may provide powerful organ
      protection. In this review, we propose the possible use of chymase inhibitors as
      agents to prevent organ damage.

PMID- 20675959
TI  - New approaches to blockade of the renin-angiotensin-aldosterone system:
      characteristics and usefulness of the direct renin inhibitor aliskiren.
AB  - Since renin inhibition interferes with the first and rate-limiting steps in the
      renin-angiotensin system, the renin step is a very attractive target for lowering
      blood pressure and minimizing target-organ damage. The newly developed direct
      renin inhibitor aliskiren has several attractive characteristics: it definitively
      reduces plasma renin activity among inhibitors of the renin-angiotensin system,
      is remarkably specific for human renin, exhibits a long half-life in plasma
      comparable to that of amlodipine, and has a high affinity for renal glomeruli and
      vasculature. Although these characteristics suggest the clinical usefulness and
      safety of aliskiren, several problems remain unsolved. Why does aliskiren have
      beneficial effects on the heart and kidneys of patients treated with angiotensin
      converting enzyme (ACE) inhibitors and/or angiotensin II type 1-receptor blockers
      (ARBs)? Is the blood-pressure-lowering effect of aliskiren dependent on the
      plasma renin activity? Does aliskiren exert a possible adverse effect via
      (pro)renin receptor-dependent intracellular signals? Here, we review the
      characteristics and usefulness of aliskiren and discuss the current issues
      associated with this direct renin inhibitor.

PMID- 20675960
TI  - New approaches to blockade of the renin-angiotensin-aldosterone system: overview
      of regulation of the renin-angiotensin-aldosterone system.
AB  - The critical role played by the renin-angiotensin-aldosterone system (RAAS) in
      the regulation of blood pressure and body fluid homeostasis has been well
      recognized. Angiotensin (Ang) II and aldosterone are the most powerful
      biologically active products of the RAAS, although there are also other bioactive
      Ang peptides involved in this system, including AngIII, AngIV, and Ang1-7. In
      addition to their physiological roles, AngII and aldosterone induce inflammation,
      cell growth, mitogenesis, apoptosis, migration, and differentiation; regulate
      gene expression of bioactive substances; and activate multiple intracellular
      signaling pathways, all of which contribute to cardiovascular tissue injury.
      During the last decade, both clinical and preclinical studies have demonstrated
      that various pharmacological interventions of the RAAS exert blood pressure
      independent cardiovascular-protective effects. In this Forum Minireview entitled
      "New approaches to blockade of the renin-angiotensin-aldosterone system", we will
      discuss the impact of RAAS inhibitors on prevention of the development of
      hypertension and cardiovascular diseases. Before going into details about the
      insights into RAAS inhibition that each of the four groups will provide, we
      herein briefly overview our current understanding of regulation of the
      circulating RAAS.

PMID- 20675961
TI  - Epigenetic characteristics of paternal chromatin in interspecies zygotes.
AB  - Both the sperm and oocyte are terminally differentiated cells, but within a very
      short post-fertilization period, their genomes are converted into a totipotent
      zygote. The process of this transformation has been studied in a number of
      mammals as well as in the pig, for which very inconsistent results have been
      published. To clarify these inconsistencies, we have used the interspecies
      intracytoplasmic sperm injection technique for embryo production and subsequent
      paternal genome remodeling evaluation. First, we injected boar sperm heads into
      ovulated and in vitro matured mouse oocytes. The boar spermatozoa consistently
      decondense in ovulated oocytes and form fully developed pronuclei with
      demethylated DNA (5-methylcytosine; 5-MeC). Additional labeling against other
      histone modifications (H3/K9 dimethylation, H3/K4 trimethylation) and HP1
      (Heterochromatin Protein 1) revealed similarity to those changes that are typical
      for natural mouse zygotes. On the other hand, no decondensation and formation of
      male pronuclei were observed, in spite of obvious oocyte activation, in in vitro
      matured oocytes. For this reason, we have evaluated the reprogramming parameters
      of in vitro matured mouse oocytes in more detail. In mouse zygotes
      (intraspecific), both pronuclei were consistently formed, but no sperm head
      chromatin demethylation was detected after 5-MeC labeling. Our observations
      suggest that porcine sperm heads are capable of undergoing active demethylation
      in in vivo matured mouse oocytes. On the other hand, in vitro matured oocytes
      possess much lower sperm remodeling capabilities.

PMID- 20675962
TI  - Ovarian follicular dynamics and hormonal changes in goats during early pregnancy.
AB  - The present study was conducted to characterize follicular development and its
      hormonal control during early pregnancy in goats. The ovaries of goats (n=8) were
      scanned daily for follicles (> or = 2 mm in diameter) and corpora lutea by
      transrectal ultrasound with blood sampling from the jugular vein for monitoring
      the hormonal changes during the first thirty-five days after mating. During early
      pregnancy, three (37.5%), four (50%) and one (12.5%) goat showed nine, eight and
      seven waves of follicular development, respectively. The corpora lutea were
      detected as early as Day 3.61 +/- 0.45 (7.47 +/- 0.43 mm) of pregnancy (Day 0=day
      of mating) and attained their maximal cross-sectional diameter (10.64 +/- 0.37
      mm) on Day 25.7 +/- 0.8 of pregnancy, respectively. A transient rise in FSH
      levels was temporally associated with the day of follicular wave emergence (up to
      three days prior to wave emergence). The plasma LH and estradiol levels were
      negatively correlated with the progesterone concentration. The rise in plasma
      immunoreactive (ir) inhibin levels was negatively correlated with the FSH
      concentration and positively correlated with the number of large-sized follicles.
      Alternatively, the mean plasma ir-inhibin levels showed a noticeable decline with
      the progression of pregnancy. The present results demonstrated that follicular
      development during early pregnancy shows a wave-like pattern, with seven to nine
      waves developing until Day 35 after breeding, and that the number of follicular
      waves can be predicted by the number of FSH peaks. The current study also
      demonstrated that the role of inhibin as an FSH regulator is maintained
      throughout early pregnancy.

PMID- 20675963
TI  - Experimental Scuticociliatosis in Japanese flounder (Paralichthys olivaceus)
      infected with Miamiensis avidus: pathological study on the possible neural routes
      of invasion and dissemination of the scuticociliate inside the fish body.
AB  - Japanese flounder (Paralichthys olivaceus) were experimentally infected with the
      highly pathogenic scuticociliate Miamiensis avidus (syn. Philasterides
      dicentrarachi) using the immersion method to clarify/identify the possible neural
      routes of entry and possible ways of dissemination of the scuticociliate in the
      fish body. Scuticociliates were observed on the skin and gills right from day 0-1
      post-infection, muscle tissue on day 2 post-infection, reached the brain, and
      spinal cord on day 3 post-infection, and systemic infection was prominent
      afterwards. Brain lesions were observed in most of the examined fish from days 3
      and 4 post-infection and considered to be the cause of the sudden increase in
      mortality. Affected fish showed varying degrees of tissue damage including severe
      epidermal and dermal necrotic lesions, necrotic myositis, encephalitis and
      myelitis. Whereas, scuticociliates were frequently observed along the optic
      and/or olfactory nerve in the fish which were accompanied by severe brain lesions
      but by minimum lesions in the gills and skin, suggesting that in addition to skin
      and/or gills, neural routes including periorbital and nasal routes may play a
      role in scuticociliate invasion to the brain. Scuticociliates were also observed
      in the peripheral nerve fibers in the muscle tissue, cranial and spinal nerves,
      cranial cavity and in the vertebral canal, suggesting that nerve fibers and/or
      cerebrospinal fluid circulation may be involved in the spread of the
      scuticociliate throughout the body in addition to the blood circulation and
      connective tissue.

PMID- 20675964
TI  - Fecal trimethylamine, lactate and volatile fatty acid concentrations and their
      relationships with diarrhea in newborn dairy calves.
AB  - To clarify the significance of fecal trimethylamine, lactate and volatile fatty
      acids (VFAs) in fermentative development of the hindgut in neonatal calves and
      the occurrence of diarrhea, 143 fecal samples (47 diarrheic, 93 normal and 3
      meconium) were collected from 58 dairy calves fed milk. An additional 20 fecal
      samples were obtained from 10 weaned calves aged 13 to 18 weeks. Fecal pH,
      trimethylamine, ammonia, lactate and VFAs were analyzed. Compared with weaned
      calves, the trimethylamine level was higher in milk-fed calves and was associated
      with a large number of cases of diarrhea, but it had little relationship with the
      fecal ammonia level. Feces collected from the youngest (<2 weeks age) calves were
      more acidic and were associated with a higher lactate concentration. Lactic
      fermentation and fecal acidity were tremendously accelerated, particularly in
      diarrhea. Despite large fluctuations, the VFA concentrations were lower in
      diarrheic than in normal feces. In diarrheic feces at the youngest stage, the
      lower proportion of n-butyrate in the VFAs was accompanied by the elevated
      proportion of acetate. However, the fermentative differences between the
      diarrheic and normal feces were less apparent with advancing age. Thus, the fecal
      lactate and VFA profiles revealed marked changes with advancing age and suffering
      from diarrhea. Upon comparison with weaned calves, the trimethylamine level was
      clearly higher in the milk-fed calves and showed huge elevations in diarrheic
      cases.

PMID- 20675965
TI  - Dietary supplementation with a probiotic fermented four-herb combination enhances
      immune activity in broiler chicks and increases survivability against Salmonella
      Gallinarum in experimentally infected broiler chicks.
AB  - Herbs including Curcuma longa, Houttuynia cordata, Prunus mume and Rubus coreanus
      have potential immune enhancing and antimicrobial effects. Probiotics also have
      antibacterial effects, and some are important in regulating the immune system.
      The aims of the present study were to evaluate the immune enhancing effects of a
      probiotic fermented four-herb combination (PFH) in broiler chicks and to
      demonstrate the prophylactic effect of PFH against Salmonella Gallinarum in
      experimentally infected broiler chicks as an initial step towards the development
      of feed supplements for promotion of immune activity and disease prevention.
      Continuous ingestion of PFH markedly increased lysozyme activity in serum and the
      spleen, peripheral blood mononuclear cell (PBMC) proliferation, the CD4(+):CD8(+)
      T lymphocyte ratio in the spleen and antibody production level in broiler chicks.
      Conversely, prostaglandin E(2) synthesis in serum and PBMC culture medium was
      significantly decreased in the PFH-fed chicks compared with the control group in
      a dose-dependent manner. In the chicks experimentally infected with S.
      Gallinarum, mortality was delayed in the 2% PFH-fed chicks. Moreover, the
      survival rates in the 2% PFH-fed group remained the highest among all the trial
      groups throughout the experimental period. Taken together, these findings suggest
      that PFH enhances immune activity in broiler chicks and increases survivability
      against Salmonella Gallinarum in experimentally infected broiler chicks, likely
      because of potent stimulation of nonspecific immune responses.

PMID- 20675966
TI  - Cognitive impairment in bipolar disorder: an overview.
AB  - Research on cognitive impairment in bipolar disorder (BD) has prompted
      significant insights about the illness. New studies challenge previous notions
      about the episodic nature of BD, and account for psychosocial disability
      unrelated to mood disturbance. This article provides a conceptual overview of the
      growing body of research on cognitive dysfunction in BD. We discuss the evidence
      in light of the complexity inherent in the connection between cognitive deficits
      and neurological abnormalities in BD. This article also addresses issues related
      to etiology, advancing an integration of neurological, clinical, cognitive, and
      psychosocial factors into a model that elucidates how these factors interact to
      negatively impact persons with BD with a more severe course of illness. Lastly,
      this article discusses implications for patient care and future considerations.

PMID- 20675967
TI  - The clinical spectrum of bipolar symptoms in epilepsy: a critical reappraisal.
AB  - Mood disorders are a frequent psychiatric comorbidity in patients with epilepsy,
      affecting quality of life and prognosis. Classic neuropsychiatric literature
      focused on major depression with data on bipolar disorder (BD) remains limited.
      However, emerging evidence suggests that mood instability, mixed irritability, or
      even mania is not uncommon in patients with epilepsy. Theoretically, epilepsy and
      BD share a number of clinical and neurobiological features. Both are episodic
      conditions that can become chronic. Moreover, the kindling phenomenon, changes in
      neurotransmitters, modifications in voltage-opened ion channels, and second
      messenger systems have been reported in both cases. This article reviews the
      available evidence regarding this intriguing comorbidity to discuss valuable
      clinical issues. In fact, recent data suggest that in most cases, bipolar
      symptoms are related to phenotype copies of BD such as peri-ictal manifestations
      (eg, preictal dysphoria or postictal mania), the so-called interictal dysphoric
      disorder, or the forced normalization phenomenon. In a minority of subjects,
      these symptoms represent treatment-emergent adverse effects of medications or
      surgery complications. Epileptologists need to be aware of the large and complex
      spectrum of bipolar symptoms in epilepsy to inform patients and their families,
      as well as to develop appropriate treatment strategies.

PMID- 20675968
TI  - Bipolar disorder: an update.
AB  - There has been a recent increase in the number of clinical trials and treatment
      options for bipolar disorder. This research has resulted in new treatment
      options. Most second-generation antipsychotics have demonstrated efficacy in the
      treatment of mania, both in monotherapy and as adjuncts to mood stabilizers. For
      bipolar depression, nearly all randomized, placebo-controlled studies have
      demonstrated that antidepressants do not provide any additional benefit to
      ongoing mood stabilizers. Additionally, antidepressants carry a risk of
      destabilization of bipolar disorder with an increase in mania, cycling, and
      chronic irritable dysphoria. Newer non-antidepressant treatments for depression
      include quetiapine, lamotrigine, modafinil, and pramipexole. These agents are
      effective for acute treatment and appear to be effective in maintenance. The
      least-studied phase of bipolar disorder is the maintenance phase. The use of
      multiple agents appears to be superior to monotherapy in relapse prevention.
      Despite the many advances in the pharmacotherapy of bipolar disorder, the overall
      prognosis of this severe illness does not appear to have changed.

PMID- 20675969
TI  - Frequency of generalized anxiety disorder in Chinese primary care.
AB  - OBJECTIVE: This study aimed to assess the frequency of generalized anxiety
      disorder (GAD) among primary care patients in China. We also determined the rate
      of comorbid major depression (MD) in patients with GAD and explored the
      differences in sociodemographic and health-related characteristics between
      patients with and without GAD. METHOD: We invited consecutive outpatients who
      presented to 4 primary care facilities in Shanghai, China to fill out a survey
      composed of a screening questionnaire based on the Diagnostic and Statistical
      Manual for Mental Disorders, Fourth Edition (DSM-IV) for GAD (GAD-7), the Zung
      Self-Rating Depression Scale (SDS), and various sociodemographic and health
      related variables. The 4 primary care facilities covered urban and suburban areas
      of the city. Patients completed the survey in the reception area as they waited
      for their medical appointment. RESULTS: The frequency of GAD in Chinese primary
      care was 4.1% (3.9% for males and 4.3% for females). This estimate was based on
      127 positive results among a total of 3073 surveys collected. Of the patients who
      screened positive for GAD, 72.4% also screened positive for MD. Patients with GAD
      were more likely to report chronic medical conditions and to attend a university
      affiliated primary care clinic. CONCLUSION: Our results showed that the frequency
      of GAD was significantly high in Chinese primary care patients. Compared with the
      GAD prevalence in Chinese general population from previously published studies,
      our findings suggest a link between GAD and health-seeking behaviors. Generalized
      anxiety disorder was also strongly correlated with MD. Integration of a routine
      GAD screening regime merits serious consideration to screen, diagnose, and treat
      patients with GAD in the primary care setting.

PMID- 20675970
TI  - Adjunctive aripiprazole, olanzapine, or quetiapine for major depressive disorder:
      an analysis of number needed to treat, number needed to harm, and likelihood to
      be helped or harmed.
AB  - OBJECTIVE: To describe the efficacy and safety of adjunctive aripiprazole,
      olanzapine, and quetiapine for major depressive disorder. DATA SOURCES: Published
      registration study reports, supplemented by clinical trial synopses as disclosed
      by manufacturers and product labeling. STUDY SELECTION: All available reports of
      studies were identified. DATA EXTRACTION: Descriptions of the principal results
      and calculation of number needed to treat (NNT) for response and remission and
      number needed to harm (NNH) for relevant dichotomous adverse outcomes were
      extracted. Likelihood to be helped or harmed (LHH) was subsequently calculated.
      DATA SYNTHESIS: Three registration studies of adjunctive aripiprazole, 5 for
      olanzapine-fluoxetine combination, and 2 for quetiapine extended-release reveal
      NNT for response and remission to range from 7 to 14 and 7 to 13, respectively,
      for adjunctive antipsychotic versus antidepressant monotherapy, depending on the
      antipsychotic and/or dose. Adverse event profiles for the 3 different adjunctive
      antipsychotics are more diverse, with adjunctive aripiprazole more strongly
      associated with akathisia (NNH, 6), adjunctive olanzapine with weight gain (NNH,
      3), and adjunctive quetiapine with somnolence (NNH, 5 for 300 mg/d and NNH, 6 for
      150 mg/d). CONCLUSIONS: Number needed to treat and NNH can be used to quantify
      efficacy and tolerability outcomes and help place various therapeutic options
      into clinical perspective. Likelihood to be helped or harmed can illustrate to
      the clinician and the patient the trade-offs between obtaining potential benefits
      versus harms. In the case of the adjunctive second-generation antipsychotics
      approved for treating major depressive disorder, these trade-offs vary greatly
      among the choices available and require careful, individualized, patient-centered
      clinical decision making.

PMID- 20675971
TI  - Use of selective serotonin reuptake inhibitors during pregnancy and risk of major
      and cardiovascular malformations: an update.
AB  - General consensus exists about the need to avoid drug intake as much as possible
      during pregnancy due to the lack of thorough evidence about the safety of
      pharmacologic treatments during gestation for both mothers and fetuses. In this
      respect, the overall safety profile of selective serotonin reuptake inhibitors
      (SSRIs) in pregnancy remains unclear. This article reviews current evidence about
      the safety of each SSRI during pregnancy in order to describe their specific
      teratogenic potential, with a particular focus on major and cardiovascular
      malformations, and to verify whether such toxicity can be considered as a class
      effect. The literature review included controlled studies and meta-analyses
      (retrieved using PsychINFO, EMBASE, and Medline from January 1966 to May 2010)
      from which the risk of major and/or cardiovascular malformations associated with
      a specific SSRI (ie, fluoxetine, paroxetine, sertraline, citalopram,
      escitalopram, and fluvoxamine) could be estimated. Although there is evidence to
      support the association between birth defects and first-trimester exposure to
      paroxetine, findings from the studies reviewed suggest a teratogenic potential of
      the whole SSRI class, consistent with preclinical evidence. These teratogenic
      effects are mainly in the heart region, and they are often described as septal
      defects. It may be suggested that the higher frequency of teratogenic effects
      reported for paroxetine might depend on specific pharmacologic features of this
      drug compared with other SSRIs, although it is difficult to test this hypothesis.
      It is noteworthy that current evidence on SSRI teratogenicity stems from studies
      affected by several methodological weaknesses (ie, lack of investigations using
      control groups of untreated depressed mothers, confounding by indication, and
      recall bias). Accordingly, we are not yet able to rule out the possibility that
      positive associations, as determined in some studies, result from analyses of
      poor quality.

PMID- 20675972
TI  - Therapeutic armamentarium for treating depression.
AB  - Depressive disorders are highly prevalent and are a leading cause of disability,
      morbidity, and mortality worldwide; however, they often remain undertreated or
      untreated. This article provides a broad overview of the many strategies for
      treating depression. More than 24 antidepressant medications and depression
      focused psychotherapies are available as first-choice options for treating
      depression. When patients have not had a satisfactory treatment response, the 2
      main strategies are switching to an alternative antidepressant therapy or adding
      a second antidepressant therapy. A large number of medication combinations have
      been reported in the literature, and some have been shown to be effective in
      controlled studies. Nonstandard alternatives to conventional antidepressant
      treatments include exercise, light therapy, sleep deprivation, and various
      complementary and alternative therapies. For more chronic and refractory forms of
      depression, various neuromodulation therapies are available or are being
      investigated. Because depressive disorders are common in primary care and other
      medical settings, medical practitioners should be aware of the therapeutic
      armamentarium available for treating depression.

PMID- 20675973
TI  - Neurocognitive correlates of emotional stimulus processing in pediatric bipolar
      disorder: a review.
AB  - Despite low prevalence rates in epidemiological studies, recent research suggests
      that bipolar disorder (BD) is being diagnosed at increasingly high rates in
      children and adolescents. To clarify the nosological boundaries of the disorder,
      studies of the clinical presentation of bipolar youth should be complemented with
      examinations of cognitive and neural functioning. More specifically, delineating
      the neurocognitive functioning of youth with BD when processing emotional stimuli
      may best elucidate how certain emotional contexts elicit symptoms that
      characterize pediatric BD. This information has the potential to clarify causes
      of pediatric BD, and to confirm the diagnosis of BD in youth. In this article, we
      discuss the affective, behavioral, cognitive, and neurological functioning of
      youth with BD when processing emotional stimuli. We focus on studies that have
      employed paradigms involving pictures and words with emotional valence, faces
      with emotional expressions, and responses to reward and punishment. The most
      consistent results on behavior are from studies involving facial stimuli, which
      find that youth with BD display a tendency to mislabel face emotions.
      Neurological data demonstrate that emotion-processing deficits in pediatric BD
      involve dysfunction within a distributed fronto-striatal-limbic network,
      including the dorsolateral and ventrolateral prefrontal cortex, anterior
      cingulate cortex, striatum, and amygdala. These data may begin to clarify why BD
      youth present with poor social functioning and deficits in regulating their
      affect and behavior.

PMID- 20675974
TI  - Overcoming the barriers to the diagnosis of dementia.
AB  - Cognitive assessment is an important skill for health care providers,
      particularly when considering the increasing prevalence of dementia. Studies have
      shown that the current diagnostic criteria for dementia are inadequate, and
      dementia is missed in both outpatient and inpatient settings. Screening tests,
      such as the Mini-Mental State Examination, detect the presence of cognitive
      impairment but will not provide a diagnosis of dementia. The gold standard for
      diagnosing dementia is the Diagnostic and Statistical Manual of Mental Disorders,
      Fourth Edition criteria. Different causes of dementia are assessed by conducting
      a detailed history and physical examination of the patient. Differentiating mild
      cognitive impairment from dementia is very important in terms of medical
      management, particularly in relation to treatment with cholinesterase inhibitors.

PMID- 20675975
TI  - Morphine sulfate and naltrexone hydrochloride extended release capsules in
      patients with chronic osteoarthritis pain.
AB  - OBJECTIVE: To assess the efficacy and safety of morphine sulfate and naltrexone
      hydrochloride extended release capsules (EMBEDA; MS-sNT), which contain morphine
      sulfate pellets with a sequestered naltrexone core, in treating patients with
      chronic, moderate-to-severe osteoarthritis (hip or knee) pain. PATIENTS AND
      METHODS: This phase 3 study had an enriched-enrollment, randomized-withdrawal,
      double-blind, multicenter design. Patients (N = 547) were titrated to an
      effective dose of MS-sNT (20-160 mg/day). Responders (n = 344) were randomized to
      12 weeks maintenance with an effective MS-sNT dose or were tapered to placebo
      over 2 weeks. The primary efficacy measure was the change from baseline (CFB) in
      diary average-pain scores (0-10 scale, Brief Pain Inventory [BPI]) from
      randomization to the last 7 days of the maintenance period. Secondary efficacy
      measures included the remaining BPI scores and Western Ontario and McMaster
      Universities (WOMAC) Osteoarthritis Index. Opioid withdrawal symptoms were
      assessed by the Clinical Opiate Withdrawal Scale (COWS) and Subjective Opiate
      Withdrawal Scale (SOWS). The study ran from January 10, 2007 through November 8,
      2007. RESULTS: MS-sNT maintained pain control better than placebo (mean CFB,
      diary average-pain score, -0.2 +/- 1.9 vs +/-0.3 +/- 2.1; P = 0.045). Change from
      baseline for MS-sNT pain-diary score (worst, least, average, current) was
      superior during the maintenance period visits, weeks 2 to 12 (P < 0.05). WOMAC
      composite score CFB was superior at most visits. MS-sNT was generally well
      tolerated, with a typical morphine safety profile. No patient taking MS-sNT as
      directed experienced withdrawal symptoms. CONCLUSION: MS-sNT provided effective
      analgesia in patients with chronic, moderate-to-severe osteoarthritis pain, with
      a safety profile typical of morphine-containing products. Naltrexone sequestered
      in MS-sNT had no clinically relevant effect when MS-sNT was taken as directed.

PMID- 20675976
TI  - Prediabetes: the importance of early identification and intervention.
AB  - Prediabetes is a state of abnormal glucose homeostasis characterized by the
      presence of impaired fasting glucose, impaired glucose tolerance, or both.
      Individuals with prediabetes are at increased risk for type 2 diabetes, compared
      with individuals with normal glucose values (normal fasting plasma glucose, < 100
      mg/dL [5.6 mmol/L]). The increased risk for cardiovascular disease in prediabetes
      is multifactorial, with etiologies including insulin resistance, hyperglycemia,
      dyslipidemia, hypertension, systemic inflammation, and oxidative stress. The
      preferred treatment is intensive lifestyle management and aggressive
      pharmacologic therapies directed toward individual coronary heart disease risk
      factors. The use of antihyperglycemic agents in this setting is a topic of
      intense debate. This review discusses the pathophysiology of prediabetes and its
      clinical implications, highlighting the importance of early identification and
      intervention.

PMID- 20675977
TI  - Causes of sudden cardiac arrest in young athletes.
AB  - Knowledge of sudden cardiac death in young athletes is imperative for all
      physicians and allied health professionals. The complete differential diagnosis
      of a young patient with sudden cardiac arrest will result in proper work-up and
      treatment. In this article, we review several etiologies of sudden cardiac death,
      including hypertrophic cardiomyopathy, arrhythmogenic right ventricular
      cardiomyopathy, Wolff-Parkinson-White syndrome, long QT syndrome, Brugada
      syndrome, and commotio cordis. Clinical findings, work-up, treatment, long-term
      management, and athlete preparticipation screening guidelines are discussed.

PMID- 20675978
TI  - Efficacy and tolerability of cyclobenzaprine extended release for acute muscle
      spasm: a pooled analysis.
AB  - OBJECTIVE: To assess the efficacy and tolerability of once-daily cyclobenzaprine
      extended release (CER) 15 and 30 mg in relieving acute muscle spasm. METHODS:
      This is a pooled analysis of 2 randomized, double-blind, placebo-controlled,
      parallel-group studies of identical design. Adults with local muscle spasm
      associated with neck/low back pain were randomized to treatment with once-daily
      CER 15 (n = 127) or 30 mg (n = 126), cyclobenzaprine immediate release (CIR) 10
      mg 3 times daily (n = 123), or placebo (n = 128) for 14 days. Primary outcome
      measures were the patient's rating of medication helpfulness and physician's
      clinical global assessment of response to therapy at day 4. RESULTS: Of 504
      patients, 330 (65.5%) completed the studies. Significantly greater improvements
      in patient's rating of medication helpfulness were reported with CER 15 and 30 mg
      versus placebo at day 4 (P < 0.025). No differences were reported between groups
      in physician's clinical global assessment. Significantly greater improvements (P
      < 0.025) were noted in patient-rated secondary measures versus placebo: relief
      from local pain at days 4 (CER 30 mg) and 8 (CER 15 and 30 mg), global impression
      of change at days 4 and 8 (CER 30 mg), and restriction of movement at day 4 (CER
      30 mg). Improvements with CER 15 and 30 mg on most efficacy measures were similar
      to CIR. There was less reported daytime drowsiness with CER 15 and 30 mg than
      with CIR (P < 0.05). Most adverse events (AEs) were mild in intensity. The most
      common AEs for all groups were dry mouth, constipation, dizziness, headache, and
      somnolence. The rate of somnolence reported as an AE was lower (P < 0.05) with
      CER 15 (0.8%) and 30 mg (1.6%) than with CIR (7.3%). CONCLUSION: Once-daily CER
      was effective in relieving acute muscle spasm based on patient's rating of
      medication helpfulness at day 4 and was generally well tolerated with a low rate
      of reported somnolence.

PMID- 20675979
TI  - Peripheral artery disease and genetics: is there a cause-and-effect relationship?
AB  - Peripheral artery disease (PAD) is a major health problem worldwide, affecting
      millions of patients. Although cardiovascular risk factors, such as diabetes,
      tobacco use, hypertension, and hypercholesterolemia have been associated with the
      development of PAD, the possible existence of an inherited genetic predisposition
      to PAD has been investigated in numerous familial aggregation studies. A link
      between genetics and PAD may open new avenues for the prevention of this morbid
      and mortal disorder. This is an overview of the potential association between
      genetics and PAD.

PMID- 20675980
TI  - Serologic markers: impact on early diagnosis and disease stratification in
      inflammatory bowel disease.
AB  - Inflammatory bowel disease (IBD) is difficult to diagnose, and differentiating
      between ulcerative colitis (UC) and Crohn's disease (CD) can be challenging.
      Overlapping symptoms of UC and CD often delay diagnosis, despite availability of
      endoscopic, radiologic, and histologic tools. This delay in diagnosis is quite
      common in clinical practice, which may also delay initiation of appropriate
      treatment. Abnormal immune responses found in IBD have led to the use of serum
      biomarkers (eg, anti-Saccharomyces cerevisiae antibody [ASCA], perinuclear
      antineutrophil cytoplasmic antibody [pANCA], antibodies to flagellin [anti
      CBir1]) to improve diagnostic confidence in IBD. These biomarkers are beginning
      to be used to stratify patients with UC and CD according to disease phenotype and
      risk of complications. Associations between quantity and quality of immune
      reactivity and severe disease phenotypes are increasingly evident. This suggests
      that serologic panels of multiple IBD biomarkers can be used to identify the
      relative risk of progression to complicated disease behaviors, and that this
      information may ultimately impact therapeutic decisions. This review discusses
      the diagnostic process and challenges in IBD, with emphasis on the role that
      serologic markers may play in addressing these challenges.

PMID- 20675981
TI  - Use of multicompartment compliance aids for elderly patients: patient viewpoints
      and hospital length of stay.
AB  - AIM: To explore elderly (aged > or = 75 years) patients' views regarding the use
      of multicompartment compliance aids (MCAs) and determine whether MCAs would
      prolong their length of hospital stay. METHODS: A cross-sectional, prospective
      study in 3 acute geriatric wards in a district general hospital in the United
      Kingdom. Patients admitted to the hospital who were found to be users of MCAs
      were interviewed about their perception of MCAs, and their length of hospital
      stay was monitored. RESULTS: A total of 1080 older patients were admitted over a
      3-month period. Only 51 (4.7%) patients were users of MCAs and constituted the
      study group. The majority (51%) of MCAs were requested by general practitioners.
      Eight (16%) patients were asked whether they wished to use the MCAs and 3 (6%)
      had formal assessment prior to MCA start. On the patients' survey, 18 (35%)
      patients did not prefer the MCA if they were given the choice. This group of
      patients had better cognitive function assessed by the Mini-Mental State
      Examination (24.4 [3.6] vs 21.8 [3.6]; P = 0.02) and were less dependent on
      social services (39% vs 67%; P = 0.04) in comparison with patients who did prefer
      the MCA. They expressed a greater lack of autonomy (94% vs 52%; P = 0.002) and
      decision making (78% vs 49%; P = 0.04). They tended to be more informed about
      their medications' names (44% vs 6%; P = 0.01), indications (28% vs 9%; P =
      0.02), and self-administration of medications (89% vs 39%; P = 0.01).
      Multicompartment compliance aids resulted in delayed discharges of 40 (78%)
      patients, with a mean of 1.3 days (standard deviation, 0.9 days; range, 0-3 days
      per patient) and a total of 65 days. CONCLUSION: The use of MCAs resulted in a
      lack of autonomy and decision making in older patients and a significant delay of
      discharges, thereby increasing hospital costs.

PMID- 20675982
TI  - Improving cardiovascular risk reduction for primary prevention--utility of
      lifetime risk assessment.
AB  - The objective of this article is to review the evidence basis for short-term risk
      assessments of overall coronary heart disease (CHD) burden as compared with
      lifetime risk estimates of CHD, based on the current medical literature. We
      reviewed literature published in the last 6 years using the terms "cardiovascular
      prevention," "Framingham risk scoring," "lifetime risk," and "cardiovascular risk
      assessment," and subsequently evaluated 98 publications to determine the
      variation in these approaches to estimate cardiovascular risk factors and impact
      on clinical decision making. The current evidence base suggests that lifetime
      risk estimates offset the significant impact of age on traditional, short-term
      risk estimates of cardiovascular risk. We conclude that the use of lifetime risk
      estimates may be more clinically meaningful than traditional, short-term risk
      estimates to assess an individual's overall risk burden, and may prevent the
      potential delay of therapeutic interventions to reduce cardiovascular events. For
      primary care, this difference may be of relevance to patients and should be
      communicated to them.

PMID- 20675983
TI  - Plasma Lp-PLA2 in acute coronary syndrome: association with major adverse cardiac
      events in a community-based cohort.
AB  - OBJECTIVE: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a useful
      inflammatory marker of cardiovascular risk, yet there are few reports on the
      prognostic significance of Lp-PLA2 as a risk factor for acute coronary syndrome
      (ACS). It is necessary to evaluate the association of Lp-PLA2 with major adverse
      cardiac events (MACE) in patients with ACS and assess its incremental value for
      risk discrimination over established risk factors and biomarkers. METHODS: One
      hundred fifty-two patients with ACS and 142 patients without coronary artery
      disease (CAD) from Shanghai Xuhui District, PRC (aged < 80 years) were enrolled
      from February 2007 to March 2008 and were followed for a median of 6 months
      (range, 4-10 months). Plasma Lp-PLA2 activity was measured at baseline with
      liquid chromatography tandem mass spectrometry. Its clinical significance was
      evaluated with existing risk indicators. RESULTS: Lp-PLA2 activity was higher in
      patients with ACS than in patients without CAD (22.36 +/- 1.23 mg/mL vs 19.74 +/-
      3.85 mg/mL; P = 0.027). During the follow-up period, 5 cases of cardiovascular
      death, 8 cases of nonfatal myocardial infarction, and 11 cases of target vessel
      revascularization occurred. Elevated Lp-PLA2 was associated with an increased
      risk of MACE (hazard ratio, 1.52; 95% confidence interval, 1.09-2.37; P = 0.033).
      The Lp-PLA2 activity level in incidental cases was higher than in nonincidental
      cases (P = 0.04). CONCLUSION: In this community-based cohort of patients with
      ACS, Lp-PLA2 was strongly and independently associated with major adverse cardiac
      events and contributed incrementally to risk discrimination.

PMID- 20675984
TI  - Sequential changes of serum aminotransferase levels in severely obese patients
      after losing weight through enrollment in a behavioral weight loss program.
AB  - Nonalcoholic fatty liver disease (NAFLD) is very prevalent in obese patients.
      However, increases in serum aminotransferase levels after weight loss have raised
      clinical concerns. This study documented sequential changes of serum
      aminotransferase levels for severely obese patients who lost a substantial amount
      of weight in a behavioral weight loss program. One hundred three severely obese
      patients who lost > 45.5 kg were treated in our clinic's weight management
      program. The prevalence of all risk factors except diabetes was higher among
      those with elevated (AE) baseline serum alanine transferase (ALT) levels than
      those with normal levels (AN). Weight losses at 8 and 24 weeks were 19.8 and 43.5
      kg in the AN group (n = 79 patients) and 21.8 and 45.5 kg in the AE group (n = 24
      patients), respectively. Total weight losses after completion of the program were
      58.4 kg in the AN group and 57.6 kg in the AE group. The baseline levels for the
      AN group were: ALT, 25.4 U/L and aspartate aminotransferase (AST)/ALT ratio,
      0.87. The baseline levels for the AE group were: ALT, 68.0 U/L and AST/ALT ratio,
      0.61. Peak ALT levels were 75.4 U/L in the AN group and 94.0 U/L in the AE group.
      The final serum ALT levels were 23.7 U/L and 27.3 U/L in the AN and AE groups,
      respectively. This severely obese population had a very high frequency of ALT
      elevations with weight loss, but elevations were transient; values usually
      returned to below baseline levels after substantial weight loss.

PMID- 20675985
TI  - Necrotizing fasciitis in a woman with a diabetic foot infection and peripheral
      neuropathy.
AB  - We report the case of a 62-year-old African American woman with poorly controlled
      diabetes who presented with the complaint of not being able to remove her
      stockings from her left foot. The patient had long-standing peripheral neuropathy
      from diabetes. Her physical examination in the emergency department was
      challenging because of extensive infection in her left lower extremity. Careful
      removal of the stockings resulted in the debridement of the lower third of her
      left leg and entire foot. Her laboratory findings were notable for a white blood
      cell count of 11.7 x 10(3) cells/mm(3) with 18% bands, an erythrocyte
      sedimentation rate of 100 mm/hour, and glycated hemoglobin of 11.5%. This case is
      unique in that the patient presented with both wet and dry gangrene of her lower
      extremities. We discuss the spectrum of infectious processes in diabetic foot
      infections and discuss the management of patients with necrotizing fasciitis.

PMID- 20675986
TI  - The many faces of type 2 diabetes.
AB  - OBJECTIVE: This report illustrates the treatment progression of a patient with
      rapidly decompensating type 2 diabetes. METHODS: The patient had to transition to
      insulin therapy within 2 years of her initial diagnosis, following only a brief
      period of glycemic control with diet management, weight loss, and oral agents.
      This relatively rapid progression to insulin requirement is occasionally seen in
      adults with typical type 2 diabetes that may classify as a number of different
      subtypes of diabetes. RESULTS: The case presented demonstrates how a simple
      stepwise approach to dose titration with basal insulin helped a patient with
      severe depletion of endogenous insulin achieve initial glycemic control, and how
      the addition of prandial insulin helped control her mealtime glycemic excursions.
      CONCLUSION: The use of basal-prandial insulin therapy is an effective option for
      patients with rapidly decompensating type 2 diabetes to achieve their glycemic
      goals without delays and to minimize associated morbidities.

PMID- 20675987
TI  - Puzzles in practice. Relapsing polychondritis (RPC).

PMID- 20675988
TI  - Antibiotic prescribing and antimicrobial resistance.

PMID- 20675989
TI  - Use of dabigatran versus warfarin for patients with atrial fibrillation.

PMID- 20675990
TI  - Association of American Medical Colleges predicts decreased number of US-trained
      physicians: profiling the response of Hofstra University School of Medicine in
      partnership with North Shore-Long Island Jewish Health System.

PMID- 20675992
TI  - [The Turkish Adult Risk Factor survey 2009: similar cardiovascular mortality in
      rural and urban areas].
AB  - OBJECTIVES: We analyzed 2009 survey of the Turkish Adult Risk Factor (TARF) Study
      to assess the distribution of all-cause and cardiovascular mortality in urban and
      rural areas and sex-specific coronary mortality in the age-bracket of 45 to 74
      years. STUDY DESIGN: The Marmara and Middle East regions have been surveyed every
      odd year in the TARF Study. In 2009, 1,655 participants were surveyed.
      Information on the mode of death was obtained from first-degree relatives and/or
      health personnel of local heath office; 960 participants underwent physical
      examination and ECG recording, and 572 subjects were evaluated on the basis of
      information obtained regarding health status. RESULTS: In the survey, 23 men and
      20 women were ascertained to have died. Twenty-one deaths were attributed to
      coronary disease and four deaths to cerebrovascular events. Assessment of the
      entire cohort in the age bracket of 45-74 years after a 19-year follow-up
      disclosed a high coronary mortality with 7.5 per 1000 person-years in men and 3.9
      in women. In a Cox regression analysis comprising 405 deaths (235 cardiovascular)
      and over 24,000 person-year follow-up, age-adjusted cardiovascular mortality was
      similar in rural and urban participants. All-cause mortality was higher in
      females living in urban areas than those living in rural areas (HR 1.41; 95% CI
      1.02-1.96). CONCLUSION: Cardiovascular mortality both in absolute terms and as a
      share of overall mortality persists to be high among Turkish adults, with similar
      rates in urban and rural areas. Age-adjusted all-cause mortality rate is higher
      among urban versus rural women.

PMID- 20675993
TI  - [EUROASPIRE III: a comparison between Turkey and Europe].
AB  - OBJECTIVES: The EUROASPIRE III survey was conducted in 2006-2007 in 22 countries
      in Europe (76 centers) to describe risk factors, lifestyle and therapeutic
      management of patients with coronary heart disease (CHD), compliance with current
      guidelines, and to document changes over time. This study aimed to assess the
      results of the EUROASPIRE III survey in terms of differences between Turkey and
      other European countries. STUDY DESIGN: The results of the EUROASPIRE III survey
      were compared with those of 17 centers from Turkey. Consecutive patients with a
      diagnosis of CHD (669 medical records, 23.8% women) were identified
      retrospectively, of which 338 patients (50.5%) were followed-up, interviewed, and
      examined at least six months after the index event (acute coronary syndrome or
      interventional procedure). RESULTS: Compared to the EUROASPIRE III data,
      recordings from Turkey's centers at discharge on classical risk factors did not
      exhibit remarkable differences; however, data on weight, height, waist
      circumference, lipid profile, glucose, and HbA1c measurements were more
      incomplete. In comparison to Europe population, the most important differences
      were observed in the higher rates of the following: young patients with
      myocardial infarction (>50 years, 20% vs. 12.7%), persistence in smoking (23.1%
      vs. 17.2%), immobility, low HDL-cholesterol (50.2% vs. 36.7%), insufficient
      follow-up by physicians after the index event (12% vs. 2.2%-except Turkey), and
      insufficient patient education. CONCLUSION: The data from the Turkey arm of the
      survey show that efforts for cardiovascular disease prevention fall short of the
      targets, similar to Europe.

PMID- 20675994
TI  - [The relationship between insulin resistance and left ventricular systolic and
      diastolic functions and functional capacity in patients with chronic heart
      failure and metabolic syndrome].
AB  - OBJECTIVES: The relationship between chronic heart failure (CHF) and insulin
      resistance (IR) has long been recognized. We examined the relationship of IR with
      left ventricular (LV) systolic and diastolic functions and functional capacity of
      CHF patients with metabolic syndrome. STUDY DESIGN: The study included 50
      nondiabetic CHF patients with metabolic syndrome (NYHA class I-III; 40 men, 10
      women; mean age 60+/-10 years). Metabolic syndrome was diagnosed according to the
      AHA/NHLBI (American Heart Association/National Heart, Lung, Blood Institute)
      criteria. Insulin resistance was determined by the homeostasis model assessment
      (HOMA). Pulse-wave Doppler echocardiography and tissue Doppler imaging were
      performed to assess LV structure and functions. RESULTS: Patients with LV
      ejection fraction <or=40% (n=25) had significantly higher NYHA functional class
      (p<0.001) compared to those with EF >40% (n=25). Fasting plasma insulin
      concentrations and HOMA-IR did not differ significantly in this respect. No
      significant differences were found in LV geometrical patterns, diastolic and
      systolic functions in patients with (HOMA >or=2.7; n=19) or without (HOMA <2.7;
      n=31) HOMA-IR. However, patients with HOMA-IR had a lower NYHA functional
      capacity (p<0.0001). HOMA-IR showed significant increases in parallel with NYHA
      functional class. CONCLUSION: Our findings suggest that IR in CHF patients with
      metabolic syndrome is not associated with LV systolic and diastolic functions,
      but is strongly linked with worsening in NYHA functional capacity.

PMID- 20675995
TI  - Differences in autonomic activity in individuals with optimal, normal, and high
      normal blood pressure levels.
AB  - OBJECTIVES: We investigated differences in autonomic activity in normotensive
      individuals having optimal, normal and high-normal blood pressure (BP) levels
      according to the guidelines of the European Society of Hypertension and European
      Society of Cardiology (ESH/ESC). STUDY DESIGN: The study included 294
      normotensive subjects (135 males, 159 females; age range 16 to 75 years) with
      similar clinical, morphometric, biochemical, electrocardiographic, and
      echocardiographic features. The subjects were classified into the following BP
      groups: group 1 (n=113) with optimal BP (<120/80 mmHg); group 2 (n=104) with
      normal BP (120-129/80-84 mmHg), and group 3 (n=77) with high-normal BP (130
      139/85-89 mmHg). All the subjects underwent 24-hour Holter monitoring to obtain
      heart rate variability (HRV) parameters of 24-hour, daytime, and nighttime
      periods. Normalized low (LFn) and high (HFn) frequency powers, and logarithmic
      (Log) values of HRV parameters were also calculated. RESULTS: On 24-hour Holter
      monitoring, heart rates were similar in three groups. Compared to group 1 and 2,
      group 3 exhibited significantly higher LF/HF (p<0.001) and LFn (p=0.001) values,
      and significantly lower HFn (p=0.001), pNN50 (p=0.001), and rMSSD (p=0.005)
      values. There were no significant differences between the groups with respect to
      daytime HRV parameters; however, nighttime LF/HF, LFn, and HFn values were
      significantly different between the groups. Log LF/HF values obtained during the
      24-hour and nighttime periods showed significant differences between group 1 and
      group 3 (for 24 hours, p<0.001; for night, p=0.001) and between group 2 and group
      3 (for 24 hours, p<0.001; for night, p=0.009), but group 1 and group 2 did not
      differ significantly in this respect (p>0.05). CONCLUSION: These findings suggest
      that subjects with high-normal BP have increased sympathetic activity and
      decreased parasympathetic activity, possibly making them more liable to
      hypertension.

PMID- 20675996
TI  - The efficiency and safety of percutaneous closure of secundum atrial septal
      defects with the Occlutech Figulla device: initial clinical experience.
AB  - OBJECTIVES: We evaluated the efficiency and safety of the Occlutech Figulla
      device in percutaneous closure of secundum atrial septal defects (ASD). STUDY
      DESIGN: The study included 28 patients (17 women, 11 men; mean age 43 years) who
      underwent percutaneous transcatheter closure using the Occlutech Figulla device
      for secundum ASDs causing a hemodynamically significant shunt. Defect size was
      estimated by transthoracic (TTE) and transesophageal (TEE) echocardiography, and
      also by balloon sizing in nine patients. The patients were followed-up for six
      months and were examined by TTE. RESULTS: The mean defect size was 20.3+/-2.1 mm
      on TTE, 22.1+/-1.9 mm on TEE, and 24.2+/-2.4 mm on balloon sizing. The mean
      device size was 26.8+/-3.6 mm (range 6 to 36 mm). The mean procedure time was
      44.7+/-21.4 minutes. The device was placed successfully in all the patients. A
      small residual flow was seen immediately after device placement in three patients
      (10.7%), which disappeared in two patients at three months, and in one patient at
      six months. During the procedure, complications were seen in four patients
      (14.3%), including transient sinus tachycardia in three patients (10.7%) and
      acute atrial fibrillation in one patient (3.6%). At six months, all the patients
      were asymptomatic. No ischemic stroke, cardiac perforation, device erosion,
      embolization, thrombus formation, or malposition of the device were observed.
      CONCLUSION: The Occlutech Figulla occluder is a safe and efficient device to
      close secundum ASDs. It may be preferred especially in patients with a high risk
      for thrombus formation.

PMID- 20675997
TI  - Acute anterior myocardial infarction in a young male patient homozygous for the
      factor V Leiden mutation.
AB  - There are several reports on the association between the factor V Leiden mutation
      and acute myocardial infarction (AMI) in young patients, in particular young
      males. A 28-year-old male patient was admitted with severe chest pain of new
      onset. He was an active smoker. His father had a history of coronary artery
      disease and AMI after the age of 45 years. There were no other major coronary
      risk factors. His electrocardiogram showed ST-segment elevation in the precordial
      leads V1 to V5. His blood pressure, pulse rate, and other clinical parameters
      were stable. Emergency coronary angiography showed a significant narrowing in the
      mid-portion of the left anterior descending (LAD) artery with a moderate
      intracoronary thrombus, and no or minimal atherosclerosis. The other coronary
      arteries were normal. Direct stenting was performed for the culprit lesion, which
      resulted in relief of obstruction and significant improvement in the LAD artery.
      DNA samples isolated from the peripheral blood were analyzed by polymerase chain
      reaction and the patient was found to be homozygous for the factor V Leiden
      mutation. Transthoracic echocardiography before discharge showed only mild
      hypokinesis of the anterior and apical segments.

PMID- 20675998
TI  - Single coronary artery arising from the right sinus of Valsalva.
AB  - Single coronary artery (SCA) is a rare congenital anomaly in which the entire
      coronary system arises from a solitary ostium. A 65-year-old male with a history
      of diabetes mellitus, hypertension, and hyperlipidemia was admitted with
      exertional angina pectoris of new onset. His physical examination, hemogram,
      thyroid function tests, chest X-ray, electrocardiogram, and transthoracic
      echocardiogram were normal. In treadmill exercise test, the patient could not
      reach submaximal heart rate due to fatigue. Coronary angiography revealed an SCA
      arising from the right sinus of Valsalva (type R-IIA). The left coronary artery
      (LCA) coursed anteriorly in front of the right ventricular outflow tract and gave
      off branches for the left anterior descending and left circumflex (LCx) arteries.
      A mild diffuse nonobstructive atherosclerotic lesion was also detected in the
      LCx. The entire SCA and the anterior course of the LCA in relation to the great
      vessels were further displayed by 16-row multislice computed tomography. The
      atherosclerotic lesion was not eligible for percutaneous intervention and the
      patient was scheduled for medical therapy with recommendation of risk factor
      modification.

PMID- 20675999
TI  - [A case of asymptomatic Brugada syndrome with type 1 ECG pattern and cardiac
      arrest: an evaluation of the prognostic value of electrophysiologic study].
AB  - Brugada syndrome is characterized by ST-segment elevation in the leads V1-3 of
      electrocardiography (ECG) in the absence of a structural heart disease. A 26-year
      old male patient was admitted with sudden cardiac arrest. Cardiopulmonary
      resuscitation was successful and he was referred to the reanimation unit due to
      unconsciousness. A year before, he was diagnosed as having Brugada syndrome with
      type 1 ECG pattern at another center, at which time electrophysiologic study
      (EPS) was not performed due to lack of symptoms and a family history of sudden
      cardiac death. In addition, family screening revealed two asymptomatic brothers
      having Brugada syndrome with type 1 ECG pattern. Medical follow-up was
      recommended to one of them. The other sibling underwent EPS at a different center
      where ventricular fibrillation was induced. An implantable cardioverter
      defibrillator (ICD) was recommended, but the patient refused. A further analysis
      of the family made at our center showed type 2 ECG changes in the father and in
      one of the cousins. Due to the development of persistent brain injury and an
      expected survival of less than a year, an ICD was not considered in the patient.
      The prognostic value of EPS is still controversial in asymptomatic patients with
      type 1 Brugada syndrome, without a family history of sudden cardiac death.

PMID- 20676000
TI  - Hypertrophic obstructive cardiomyopathy causing severe right and left ventricular
      outflow tract obstruction.
AB  - An 18-year-old male patient presented with a 3-year history of exertional
      dyspnea, dizziness, and angina. Echocardiography showed advanced hypertrophy of
      the left ventricle (LV), right ventricle (RV) free wall, and interventricular
      septum. There were apparent muscular bundles especially at the level of the right
      ventricular outflow tract (RVOT). Maximal pressure gradients across the RVOT and
      left ventricular outflow tract (LVOT) were 141 mmHg and 66 mmHg, respectively.
      There was also grade 2 aortic regurgitation. Transesophageal echocardiography and
      cardiac magnetic resonance imaging confirmed these findings. Despite treatment
      with propranolol and cibenzoline, the patient remained symptomatic with unchanged
      pressure gradients. Corrective surgery including an extensive muscular resection
      of the RVOT, minimal resection of the LVOT, and interposition of a graft patch in
      the RVOT resulted in complete disappearance of the RVOT gradient and a
      significant decrease to 28 mmHg in the LVOT gradient. During a year follow-up,
      aortic valvular insufficiency remained clinically stable and the patient was
      asymptomatic. This is the first case of hypertrophic obstructive cardiomyopathy
      with predominant RVOT obstruction treated by myectomy and patch graft
      interpositioning.

PMID- 20676001
TI  - Acute type A aortic dissection and left main coronary artery obstruction detected
      by transesophageal echocardiography.
AB  - A 63-year-old man was admitted with severe chest pain. The electrocardiogram
      demonstrated ST-segment depression in the anterior and lateral leads suggesting
      acute anterior myocardial ischemia. Contrast-enhanced thoracic computed
      tomography performed due to severe back pain showed acute dissection of the
      descending aorta. Coronary angiography showed normal coronary arteries.
      Transesophageal echocardiography revealed a Stanford type A aortic dissection
      involving the left main coronary ostium and causing left main coronary occlusion.
      The dissected flap caused partial obstruction of the coronary ostium and
      occasional separation of the lumen, resulting in nonsustained ventricular
      tachycardia. At emergency operation, the entry of the dissection was seen in the
      ascending aorta and the dissection extended throughout almost the entire sinus of
      Valsalva and the left main coronary trunk. The aortic flap was seen in the
      coronary ostium. Both the right and left coronary arteries were prepared widely
      and sutured directly to a composite graft. The ascending aorta was replaced with
      a composite graft through a Bentall procedure. Descending aortic repair was
      planned for a subsequent operation. The patient was hemodynamically stable for
      three weeks, but then developed respiratory insufficiency due to severe
      nosocomial pneumonia and died one month after the operation.

PMID- 20676002
TI  - [Percutaneous closure of a femoral arteriovenous fistula with an endovascular
      stent graft: a case report].
AB  - A 25-year-old male patient underwent primary femoral artery repair following a
      gunshot injury. Postoperative examination showed a thrill and bruit in the right
      femoral region. Peripheral angiography performed under right femoral Doppler
      ultrasound guidance revealed an arteriovenous fistula between the right
      superficial femoral artery and femoral vein. Through selective angiography from
      the left femoral artery, an endovascular stent was implanted in the right femoral
      artery. Control contrast injection showed near-total closure of the fistula and
      Doppler ultrasonography on the following day showed total closure.

PMID- 20676003
TI  - [Arrhythmogenic cardiomyopathy with predominant left ventricular involvement].
AB  - Arrhythmogenic right ventricular cardiomyopathy is a relatively well-defined
      clinical entity. This disease is characterized with right ventricular involvement
      and is an important cause of sudden cardiac death in young patients. However,
      arrhythmogenic cardiomyopathy with left-dominant involvement has recently been
      better described in the literature. This new presentation may be confused with
      other diseases such as idiopathic dilated cardiomyopathy. This review outlines
      left-dominant arrhythmogenic cardiomyopathy in the light of the most recent
      information.

PMID- 20676004
TI  - Left atrial myxoma demonstrated by real-time three-dimensional transesophageal
      echocardiography.

PMID- 20676005
TI  - A giant left atrium.

PMID- 20676006
TI  - [Isolated right ventricular myocardial infarction and saccular focal aortic root
      dissection leading to right coronary artery ostial obstruction in a patient
      receiving chemotherapy for small cell lung cancer].

PMID- 20676007
TI  - [A consequence of untreated hypertension: giant aneurysm of the aortic arch].

PMID- 20676008
TI  - [Mass surrounding the heart: findings of transthoracic echocardiography and
      computed tomography].

PMID- 20676009
TI  - Complications encountered in proximal humerus fractures treated with locking
      plate fixation.
AB  - OBJECTIVES: We evaluated the complications encountered following locking plate
      fixation of proximal humerus fractures. METHODS: The study included 103 patients
      (70 females, 33 males; mean age 62 years; range 21 to 90 years) who were treated
      with open reduction and locking plate fixation for proximal humerus fractures
      between September 2005 and April 2009. Fixation was performed using the PHILOS
      locking plate in 93 patients, and S3 humerus plate in 10 patients.
      Postoperatively, a shoulder-arm sling was applied for six weeks and a standard
      rehabilitation program was used in all the patients. Intraoperative, acute
      postoperative, and late postoperative complications were assessed on radiographs.
      Varus inclination was defined as less than 120 degrees of the inclination angle
      on immediate postoperative radiographs, and varus displacement as postoperative
      increases in the varus angle. The mean follow-up period was 19 months (range 2
      weeks to 43 months). RESULTS: Complications were seen in 10 patients (9.7%; mean
      age 67 years). The PHILOS plate was used in nine patients and S3 plate was used
      in one patient. Five patients (4.9%) had varus inclination with a mean
      inclination angle of 112.6 degrees (range 105 degrees to 118 degrees), four
      patients (3.9%) developed varus displacement with a mean inclination angle of
      102.5 degrees (range 95 degrees to 110 degrees), and intra-articular screw
      penetration was seen in five patients (4.9%). The remaining complications were
      fixation failure (n=1, 1%), implant fracture (n=1), and deep infection (n=1).
      Screw penetration exceeded 3 mm in three patients, requiring revision surgery.
      The mean ages of patients with varus inclination, varus displacement, and screw
      penetration were 76.6, 74.4, and 71 years, respectively. Three patients with
      varus inclination (60%) developed varus displacement. Screw penetration was
      observed in three patients (60%) with varus inclination, and in all patients with
      varus displacement. The mean Constant-Murley shoulder score was 67.8 (range 50 to
      90) in patients who developed a complication. CONCLUSION: Our findings show that
      locking plate and screw systems represent a significant treatment option in the
      treatment of comminuted and displaced humerus fractures, with low complication
      rates. Accurate indication, protection of the head's inclination angle through
      appropriate surgical approach and proper technique, and fine calculation of screw
      length are essential for successful functional results.

PMID- 20676010
TI  - Locking plate fixation of three- and four-part proximal humeral fractures.
AB  - OBJECTIVES: We evaluated the functional results of open reduction and internal
      fixation with a locking plate in patients with three- or four-part fractures of
      the proximal humerus. METHODS: We reviewed 32 consecutive patients (22 women, 10
      men; mean age 63 years; range 29 to 82 years) who were treated with open
      reduction and internal fixation using the PHILOS locking plate for comminuted
      proximal humeral fractures. According to the Neer classification, 12 patients
      (mean age 56 years) had three-part fractures, 19 patients (mean age 67 years) had
      four-part fractures, and one patient had a four-part fracture dislocation. Ten
      patients were in the age group of <60 years, 22 patients were in the age group of
      60=or>years. All the patients were evaluated with plain radiographs
      preoperatively; in addition, computed tomography was used in 14 patients in whom
      articular surface and tuberculum displacement could not be assessed adequately.
      The operation was performed through a standard deltopectoral approach, and
      minimal soft tissue dissection was used aiming not to impair vascularization of
      the fracture fragments. A cerclage wire was used to help reduction in 12
      patients. An oblique screw was inserted to stabilize the medial colon in cases in
      which medial cortical contact was insufficient. Bone grafting was not used in any
      of the patients. Active-assisted and passive exercises of the shoulder were
      initiated on the second postoperative day. Active abduction to 90 degrees was
      allowed two weeks after surgery. During follow-up, implant failure, loss of
      reduction, malunion, and bone healing were assessed on plain radiographs. Bone
      scintigraphy was performed after 12 postoperative months for the detection of
      avascular necrosis. The results were assessed using the Constant shoulder score.
      The mean follow-up period was 25 months (range 18 to 36 months). RESULTS: An
      anatomic or near-anatomic reduction was obtained in 29 patients (90.6%). In two
      patients, the fractures were fixed in a varus position, and in one patient, the
      greater tubercle was displaced proximally. All fractures united in a mean of
      three months (range 2 to 5 months). The mean Constant score of the patients was
      79.5 (range 50 to 100). The results were excellent in 13 patients (40.6%), good
      in nine patients (28.1%), fair in eight patients (25%), and poor in two patients
      (6.3%). The mean Constant scores were 88.3 (range 69 to 100) and 74.2 (range 50
      to 100) in three-part and four-part fractures, and 88.3 (range 71 to 100) and
      75.5 (range 50 to 100) in the age groups of <60 years and =or>60 years,
      respectively. Constant scores showed significant differences with respect to the
      number of comminution and age groups (p=0.03). Avascular necrosis was observed in
      two patients. None of the patients had reduction loss, implant failure, deep
      infection, or neurovascular injury, and none required implant removal.
      CONCLUSION: Preservation of humeral head vascularity through minimal soft tissue
      dissection, fixation with a locking plate, and early postoperative motion were
      effective in decreasing potential complications following surgical treatment of
      three- and four-part proximal humeral fractures. The degree of fracture
      comminution and age of the patients affect functional results significantly.

PMID- 20676011
TI  - Functional results of conservative therapy accompanied by interscalane brachial
      plexus block and patient-controlled analgesia in cases with frozen shoulder.
AB  - OBJECTIVES: We evaluated the efficacy of simultaneous interscalene block and
      catheter analgesia applied as an aid to conservative treatment in improving
      shoulder functions in patients with frozen shoulder. METHODS: Three patients (2
      women, 1 man; mean age 47 years) with frozen shoulder underwent conservative
      treatment including manipulation under interscalene brachial plexus block and
      subsequent rehabilitation under catheter analgesia to improve shoulder range of
      motion and function. Following manipulation under interscalene block, the
      patients were hospitalized for 15 to 28 days (mean 21 days) for an exercise
      program performed by a physiotherapist and orthopedist at least twice a day under
      interscalene catheter analgesia. Thirty minutes before each rehabilitation
      session, patient-controlled analgesia was administered via a pain relief pump.
      Active and passive range of motion (ROM) were measured and the severity of pain
      was rated using a visual analog scale (VAS) prior to and following interscalene
      block, during the exercise program, and at the end of the treatment. Functional
      assessments were made before and after treatment using the University of
      California in Los Angeles (UCLA) Shoulder Scale. The exercise program under
      interscalene analgesia was performed until pain-free and sufficient active
      movements were obtained, with at least 80% improvement in active and passive
      motion, a VAS score of 0-2, and an UCLA score of >27. RESULTS: Compared to
      pretreatment values, the ROM values showed remarkable increases at the end of the
      treatment. Active ROM reached at least 30 degrees external rotation, 40 degrees
      internal rotation, 150 degrees flexion, 45 degrees extension, and 100 degrees
      abduction in all cases. On presentation, the VAS scores of all cases were 10 for
      both active and passive movements, whereas they ranged from 0 to 2 on discharge.
      The mean UCLA score increased from 12.3 to 30.3 after treatment. Immediately
      after the interscalene block, two patients exhibited signs of Horner's syndrome
      which resolved spontaneously within an hour without the need for treatment. No
      complications or catheter-related problems such as infection, break-off, or
      displacement developed throughout the treatment period. There was no requirement
      for additional analgesia. CONCLUSION: In patients with frozen shoulder,
      interscalene block and continuous patient-controlled analgesia via an
      interscalene catheter provided sufficient analgesia and contributed to the
      recovery of shoulder functions through an effective and safe exercise program,
      with no side effects or complications. However, further studies are needed to
      assess the feasibility of home applications of interscalene patient-controlled
      analgesia to increase cost-effectiveness and patient satisfaction.

PMID- 20676012
TI  - Utilization of axillary brachial plexus block in the postoperative rehabilitation
      of intra-articular fractures of the distal humerus.
AB  - OBJECTIVES: An effective rehabilitation program is essential to prevent joint
      stiffness and regain range of motion after surgical treatment of intra-articular
      fractures of the distal humerus. We evaluated the effect of a physiotherapy
      program on functional results, that involved passive resistive stretching
      exercises performed under axillary brachial plexus block after radiographic
      observation of bone union of intra-articular fractures of the distal humerus
      treated with open reduction and internal fixation. METHODS: The study included 21
      patients (7 females, 14 males; mean age 34+/-5 years; range 21 to 57 years) who
      underwent open reduction and internal fixation for intra-articular fractures of
      the distal humerus. All the patients had closed fractures. Six patients had AO
      type C1, six patients had C2, and nine patients had C3 fractures. Surgical
      treatment consisted of a posterior incision, olecranon osteotomy, and fixation of
      the metaphyseal fragments using two reconstruction plates placed medially and
      laterally. Active range of motion exercises were started on the third
      postoperative day. To prevent early development of heterotopic ossification,
      passive range of motion exercises were avoided. Active stretching exercises were
      initiated three weeks after surgery. Upon radiographic observation of bone union,
      axillary brachial plexus block was performed. The physiotherapy program involved
      passive stretching exercises during nerve block, and active weight exercises
      after recovery from motor block. The catheter remained in the axillary region for
      three months, during which functional rehabilitation was continued 2-3 times a
      week on an outpatient basis. Functional results were evaluated according to the
      criteria of Jupiter et al. after a mean follow-up period of 31 months (range 24
      to 46 months). RESULTS: All fractures united within a mean of 11.9 weeks (range 9
      to 17 weeks) except for one type C3 fracture. Functional results were excellent
      in 10 patients (47.6%), good in eight patients (38.1%), moderate in two patients
      (9.5%), and poor in one patient (4.8%). Two patients with a moderate outcome had
      associated multiple fractures in the ipsilateral extremity. Distribution of the
      functional results according to the type of fractures were 4 excellent, 2 good in
      type C1; 4 excellent, 2 good in C2; and 2 excellent, 4 good, 2 moderate, and 1
      poor in C3 fractures. The mean loss of elbow extension was 16 degrees. The mean
      elbow flexion, pronation, and supination were measured as 131 degrees, 90
      degrees, and 75 degrees, respectively. None of the patients had nonunion at the
      olecranon osteotomy site, superficial or deep infection, or heterotopic
      ossification. Three patients developed transient ulnar nerve neuropraxia that
      resolved spontaneously during the follow-up period. There were no complications
      related to axillary catheterization. CONCLUSION: Following surgical treatment of
      intra-articular fractures of the distal humerus, a regular and pain-free
      physiotherapy program performed under axillary brachial plexus block on an
      outpatient basis increases patient compliance and enables early return to daily
      activities.

PMID- 20676013
TI  - Selective Kirschner wiring for displaced distal radial fractures in children.
AB  - OBJECTIVES: This study was designed to evaluate our departmental policy of
      plaster immobilization and selective Kirschner (K) wiring for the management of
      displaced distal radius fractures in children. METHODS: On a retrospective basis,
      we evaluated a consecutive series of 112 childhood displaced distal radius
      fractures (108 patients; 77 boys, 31 girls; mean age 10.5+/-2.6 years; range 5 to
      16 years) presenting with clinical deformity during a two-year period. There were
      97 incompletely displaced (86.6%), and 15 completely displaced (13.4%) fractures.
      All the fractures were managed with manipulation under general anesthesia and
      plaster immobilization. Additionally, K-wire fixation was performed following
      manipulation in seven (46.7%) of the completely displaced fractures. The mean
      follow-up period was 1.1 years (range 10 weeks to 2 years). RESULTS: The mean
      angulation of fractures prior to manipulation was 21.5+/-10.1 degrees, it
      decreased to 2.4+/-4.8 degrees following manipulation. Remanipulation was
      required in 11 fractures (9.8%) based on clinical and radiographic findings of
      redisplacement. Of these, eight fractures (8.3%) were incompletely displaced, and
      three fractures (20%) were completely displaced. All completely displaced
      fractures that required remanipulation had been additionally treated with K-wire
      fixation. Fractures requiring further treatment had a mean angulation of 17.1+/
      5.8 degrees prior to remanipulation, and a mean residual angulation of 4.7+/-6.0
      degrees at final radiographic assessment. A perfect fracture reduction was
      achieved in all the patients with a Salter-Harris II injury (n=22), and none of
      these patients required remanipulation. However, the quality of initial reduction
      was not associated with the development of redisplacement. There was no
      significant difference between isolated distal radius fractures (n=58) and
      combined radius and ulna fractures (n=32) with respect to remanipulation rate and
      final angulation (p>0.05). Final radiographs showed a significantly greater
      angulation in fractures which were initially completely displaced in comparison
      with those that were incompletely displaced (8.2+/-7.1 degrees vs. 4.2+/-5.7
      degrees; p=0.024), but this was not of clinical significance. None of the
      patients had radial shortening and no K-wire related complications were
      encountered. CONCLUSION: Our data suggest that there should be other factors
      involved in the development of redisplacement and the need for remanipulation
      other than the degree of fracture displacement and the quality of initial
      reduction. Selective K-wire fixation in displaced fractures does not seem to
      decrease redisplacement and remanipulation rates.

PMID- 20676014
TI  - The relationship between morphometric parameters and Trendelenburg sign following
      the Hardinge incision.
AB  - OBJECTIVES: We evaluated the relationship between morphometric parameters such as
      height, weight, and body mass index with the development of the Trendelenburg
      gait following the Hardinge approach, which is one of the most commonly used
      approaches in total hip arthroplasty. METHODS: The study included 59 patients (43
      women, 16 men; mean age 55 years; range 37 to 74 years) who underwent total hip
      arthroplasty via the Hardinge approach for primary coxarthrosis. The patients
      were examined postoperatively at 15 days, and at the end of the first and third
      months. The mean follow-up period was 24.3 months (range 12 to 37 months). The
      height, weight, and body mass index values of the patients with and without a
      positive Trendelenburg sign were compared. RESULTS: The Trendelenburg sign was
      positive in 19 patients (32.2%) following total hip arthroplasty with the
      Hardinge approach and persisted for a mean of 8.3 months (range 4-14 months).
      Patients with a positive Trendelenburg sign had a mean height of 157.4 cm (range
      151 to 173 cm), mean weight of 82.5 kg (range 70 to 108 kg), and mean body mass
      index of 33.2 kg/m(2) (range 25.4 to 30.5 kg/m(2)). The corresponding figures in
      patients without a Trendelenburg sign were as follows: 166.3 cm (range 158 to 180
      cm), 79.4 kg (range 72 to 94 kg), and 28.7 kg/m(2) (range 21.6 to 30.5 kg/m(2)).
      There was no significant difference between the two patient groups with respect
      to weight, but height and body mass index showed highly significant differences
      (p<0.0001). CONCLUSION: Based on our finding that patients having a significantly
      shorter height and greater body mass index sustained Trendelenburg positivity for
      quite a long time, we recommend that these two factors be taken into
      consideration in the preoperative evaluation of patients for total hip
      arthroplasty with the Hardinge approach. Thus, the use of the Hardinge approach
      in total hip arthroplasty may not be convenient in short subjects having
      borderline obesity.

PMID- 20676015
TI  - Radiographic and functional results of osteosynthesis using the proximal femoral
      nail antirotation (PFNA) in the treatment of unstable intertrochanteric femoral
      fractures.
AB  - OBJECTIVES: We evaluated the radiographic and functional results of the proximal
      femoral nail antirotation (PFNA) system in patients with unstable
      intertrochanteric femoral fractures. METHODS: The study included 45 patients (25
      women, 20 men; mean age 72 years; range 27 to 97 years) who underwent
      osteosynthesis using the PFNA for unstable intertrochanteric femoral fractures.
      The fractures were in the right hip in 25 patients, and in the left hip in 20
      patients. The fractures were classified according to the AO system. One patient
      had an open fracture due to firearm injury (Gustilo-Anderson 3A). The patients
      underwent surgery within a mean of eight days (range 2 to 21 days) from injury.
      The mean hospital stay was 13.5 days (range 4 to 25 days). Closed reduction was
      achieved in all the patients. The results were assessed clinically and
      radiographically. The neck-shaft angle of the femur (collodiaphysial angle) and
      the tip-apex distance were measured. The position of the helical screw within the
      femoral head was determined using the method of Cleveland and Bosworth. Clinical
      evaluation was made using the Harris hip score. Perioperative and postoperative
      complications were recorded. The mean follow-up period was 17.3 months (range 6
      to 23 months). RESULTS: The mean operation time was 37.8 min (range 22 to 118
      min) and the mean blood loss was 225 ml (range 150 to 450 ml). During surgery,
      femoral shaft fracture occurred in three patients, and greater trochanter
      fracture occurred in nine patients. Union was obtained in all the patients.
      Reduction was poor in four patients (8.9%), acceptable in seven patients (15.6%),
      and good in 34 patients (75.6%). The mean collodiaphysial angle was 136.7 degrees
      (range 125 degrees to 148 degrees). The tip-apex distance was <25 mm in 36
      patients (80%), and =or>25 mm in nine patients (20%). The position of the helical
      screw in the femoral head was appropriate in 38 patients (84.4%). Postoperative
      complications included secondary varus (n=2, 4.4%), calcification at the tip of
      the greater trochanter (n=7, 15.5%), sensitivity over the fascia lata (n=7),
      medial thigh pain (n=11, 24.4%), and screw cut-out (n=1, 2.2%). Nine patients
      developed femoral shortness (mean 9.4 mm; range 8 to 13 mm). Screws showed
      lateral displacement in five patients (11.1%), which was less than 5 mm in four
      patients. Secondary surgery was required in four patients (8.9%). The mean Harris
      hip score was 77.8. Harris hip scores were very good in 11 patients (24.4%), good
      in 19 patients (42.2%), moderate in nine patients (20%), and poor in six patients
      (13.3%). CONCLUSION: Due to advantages of high union rate, early postoperative
      mobilization, and short operation time, PFNA osteosynthesis is the method of
      choice for surgical treatment of unstable intertrochanteric femoral fractures..

PMID- 20676016
TI  - Short-term results of the Oxford phase 3 unicompartmental knee arthroplasty for
      medial arthritis.
AB  - OBJECTIVES: We evaluated short-term results of the Oxford phase 3
      unicompartmental knee arthroplasty (UKA) in patients with medial compartment
      arthritis. METHODS: The study included 38 patients (28 females, 10 males; mean
      age 67 years; range 56 to 75 years) who underwent UKA for isolated medial knee
      osteoarthritis. At the time of surgery, 28 patients were in the age group of 56
      64 years, and 10 patients were in the age group of 65-75 years. All the patients
      had Ahlback grade 2 primary medial compartment arthritis that had been
      unresponsive to conservative treatment. None of the patients had symptoms of
      patellofemoral arthrosis. Patients underwent UKA with the Oxford phase 3 cemented
      meniscal-bearing unicondylar prosthesis using minimally invasive surgery. The
      results were assessed preoperatively and at final controls according to the Knee
      Society clinical and functional rating system. Postoperative radiographic
      evaluations were made according to the Oxford criteria. The mean follow-up period
      was 24 months (range 18 to 32 months). RESULTS: The mean preoperative active knee
      flexion increased from 121.8 degrees (range 110 degrees to 130 degrees ) to 130.9
      degrees (range 120 degrees to 140 degrees) postoperatively (p<0.05). There was no
      limitation in knee extension both pre- and postoperatively. The mean preoperative
      and postoperative knee scores were 64.6 (range 47 to 80) and 97.5 (range 89 to
      100), and the mean functional scores were 59.6 (range 45 to 80) and 92.1 (range
      70 to 100), respectively (p<0.05). All the patients had an excellent knee score,
      while functional scores were excellent in 27 patients (71.1%) and good in 11
      patients (28.9%). Postoperative radiographic measurements showed that the
      position of the femoral components was within acceptable ranges in all the
      patients with a mean of 3 degrees valgus (range 5 degrees valgus to 8 degrees
      varus) and 0.5 degrees extension (range 3 degrees extension to 2 degrees
      flexion). The positioning of the femoral components in relation to the mechanical
      axis was central in 30 patients and 2-mm lateral (range 2 mm medial to 4 mm
      lateral) in eight patients. The position of the tibial components was also within
      acceptable ranges in all the patients with a mean of 1.5 degrees varus (range 2
      degrees varus to 2 degrees valgus) and a mean posterior inclination of 6.2
      degrees (range 5 degrees to 7 degrees). All the tibial components showed full
      congruency with the medial, lateral, anterior, and posterior planes, except for
      one which had a 4-mm undersizing in the anterior plane. The polyethylene insert
      was central and parallel to the tibial component in all the patients. No
      osteophytes or cement debris that might lead to impingement were observed. All
      the components remained in position until the final controls. Complications such
      as insert dislocation, infection, pulmonary embolism, deep venous thrombosis, or
      neurovascular injury were not observed. None of the patients required revision
      surgery. CONCLUSION: Our findings show that, with proper patient selection and
      strict adherence to the surgical technique, short-term results of the Oxford
      phase 3 unicompartmental knee prosthesis are excellent or good in the treatment
      of medial compartment osteoarthritis.

PMID- 20676017
TI  - Interposition arthroplasty in the treatment of hallux rigidus.
AB  - OBJECTIVES: We evaluated the outcomes of interposition arthroplasty performed for
      the treatment of hallux rigidus. METHODS: The study included 19 feet (4 left, 15
      right) of 17 patients (14 females, 3 males; mean age 61+/-5 years; range 55 to 71
      years) who were treated with interposition arthroplasty for hallux rigidus.
      According to the grading system of Coughlin and Shurnas, 18 feet were grade 3,
      one foot was grade 4. One-third of the base of the proximal phalanx was resected
      at surgery. Preoperative and postoperative radiographic assessments included the
      measurements of the joint space width of the first metatarsophalangeal (MTP)
      joint, hallux valgus angle, and intermetatarsal angle. Clinical evaluations were
      made using the AOFAS (American Orthopaedic Foot and Ankle Society) hallux
      metatarsophalangeal-interphalangeal scale. Postoperative satisfaction levels of
      the patients were questioned. The mean follow-up period was 21 months (range 9 to
      32 months). RESULTS: According to the AOFAS scale, the results were excellent in
      seven feet (36.8%), good in nine feet (47.4%), and fair in three feet (15.8%),
      with excellent and good results accounting for 84.2%. The mean total AOFAS score
      increased by 24.6 points postoperatively (p<0.05). The mean range of motion of
      the first MTP joint improved significantly from preoperative 24.2+/-5.4 degrees
      (range 10 degrees to 30 degrees) to postoperative 54.3+/-9.4 degrees (p<0.05).
      The mean joint space width of the first MTP joint was 1.0+/-0.3 mm (range 1 to 2
      mm) preoperatively, it increased to 3.0+/-1.1 mm (range 1 to 5 mm) on final
      radiographs (p<0.05). The mean hallux valgus angle decreased from preoperative
      13.8 degrees (range 9 degrees to 17 degrees) to postoperative 10.2 degrees (range
      4 degrees to 13 degrees), and the mean intermetatarsal angle increased from
      preoperative 10.5 degrees (range 8 degrees to 14 degrees) to postoperative 11.2
      degrees (range 8 degrees to 15 degrees). Patient satisfaction levels were very
      good in nine feet (47.4%), good in seven feet (36.8%), moderate in one foot
      (5.3%), and poor in two feet (10.5%). Complications included metatarsalgia
      aggravated by long walks (n=11, 57.9%), hypoesthesia of the big toe (n=3, 15.8%),
      and loss of ground contact of the big toe (n=15, 79%). The push-off power of the
      big toes was measured as 3/5 in five cases, 4/5 in 11 cases, and 5/5 in three
      cases. None of the patients developed infection or osteonecrosis postoperatively.
      CONCLUSION: Interposition arthroplasty is an appropriate surgical treatment
      method for hallux rigidus for elderly patients with low functional capacity.

PMID- 20676018
TI  - Validity of the Turkish version of the Kujala patellofemoral score in
      patellofemoral pain syndrome.
AB  - OBJECTIVES: Patellofemoral pain syndrome is one of the most common knee problems,
      with major effects on quality of life and function. The Kujala patellofemoral
      score is a functional evaluation instrument to evaluate knee problems related to
      the patellofemoral system. The aim of this study was to evaluate the validity of
      the Turkish version of the Kujala patellofemoral score in patients with
      patellofemoral pain syndrome. METHODS: After obtaining permission from Kujala et
      al., the Kujala patellofemoral score was translated into Turkish. The translated
      version was administered to 40 patients (32 women, 8 men; mean age 33+/-12 years;
      range 17 to 54 years) twice at a two-week interval to test internal consistency
      and test-retest reliability of the scale. All the patients had patellofemoral
      pain syndrome and did not receive any treatment before administration of the
      scale. Cronbach's alpha coefficient was used to assess internal consistency and
      Spearman's correlation analysis was used to assess test-retest reliability.
      RESULTS: Cronbach's alpha calculated for internal consistency of the Kujala
      patellofemoral score was 0.84. Correlation coefficients of the items to estimate
      test-retest reliability ranged from 0.613 (p=0.004) to 1.000 (p=0.000), with the
      mean correlation coefficient of 0.944 (p=0.000). CONCLUSION: There has been no
      functional assessment scale validated for Turkish patients with patellofemoral
      pain syndrome. Internal consistency of the Turkish version of the Kujala
      patellofemoral score showed good reliability and test-retest results showed high
      reliability, suggesting that it is an appropriate functional instrument for
      Turkish patients with patellofemoral pain syndrome.

PMID- 20676019
TI  - The use of an absorbable collagen cover (NeuraWrap) improves patency of
      interpositional vein grafts.
AB  - OBJECTIVES: Autologous interpositional vein grafts are used in peripheral
      arterial bypass procedures. Sudden exposure of vein grafts to arterial blood
      pressure is associated with increased wall tension leading to overdistension of
      the graft and changes in flow patterns. Overdistension of vein grafts often
      results in anastomotic leaks, thrombosis, and loss of patency. This study was
      designed to evaluate the use of a biodegradable collagen cover as a means of
      preventing overdistension of venous bypass grafts in a rat model. METHODS: Twenty
      two Sprague-Dawley female rats weighing 250-350 g were randomly assigned to two
      groups: study group (n= 15) and control group (n=7). In all the rats, a 10-mm
      segment of the left femoral vein was harvested and used as a graft in repair of a
      right femoral artery injury. Following this procedure, control rats remained
      untreated. After completion of the femoral artery repair in the study group, the
      graft was wrapped with a collagen cover of appropriate length (NeuraWrap Nerve
      Protector) and sutured to form a tube around the vein graft. At the end of the
      procedure, the intensity and duration of bleeding, and vessel patency were
      recorded and the proximal and distal arterial segments were examined by Doppler
      ultrasonography. All observations and measurements were repeated at 1 and 2 hours
      after surgery. After the second hour, all the rats were sacrificed and vein graft
      samples with the arterial portions were removed for histological study. RESULTS:
      After removal of the vascular clamps of the control group, a sudden distension
      was observed in all the vein grafts. In this group, bleeding at the anastomosis
      site lasted for 1 to 3 minutes and was followed by ballooning of the grafts. In
      the study group, however, none of the samples exhibited distension and
      ballooning. There was no bleeding in 11 samples at all, and bleeding time was
      less than one minute in the remaining four samples. In the control group, only
      one graft was patent at two hours, one of the grafts was occluded after only
      three minutes. In the study group, all the grafts were patent and no thrombosis
      was noted. The mean blood flow velocity of the control group measured at 0 hour
      by Doppler ultrasonography was 0.93+/-0.33 cm/sec in the proximal artery, and
      0.73+/-0.44 cm/sec in the distal artery. The mean blood flow velocities in the
      proximal and distal arteries of the study group were as follows, respectively: at
      0 hour: 0.45+/-0.27 and 0.46+/-0.22 cm/sec; at 1 hour: 0.40+/-0.22 and 0.62+/
      0.40 cm/sec; and at 2 hours: 0.55+/-0.22 and 0.64+/-0.37 cm/sec. CONCLUSION:
      Prevention of overdistension of vein grafts with the use of an external cover
      decreases anastomotic leaks, protects the intimal media, maintains blood flow,
      reduces the incidence of thrombosis, and thus provides a higher patency rate.

PMID- 20676020
TI  - An unusual cause of recurrent joint effusions: nonhemophilic hemosiderotic
      synovitis of the knee.
AB  - A 20-year-old female presented with a painful swelling in the right knee and
      snapping sensation on joint motion that appeared without trauma and recurred
      several times. She had no history of a bleeding disease or trauma. Physical
      examination showed no signs of rash or temperature change or systemic or local
      findings of an infection. The knee was tender and knee motion was painful, with
      90 degrees of flexion and full extension. The ballottement test was positive. All
      laboratory tests including rheumatologic and bleeding parameters were normal.
      Joint effusion analysis was normal except for its rusty-brown color. Magnetic
      resonance imaging showed synovial hypertrophy and grade 2 degeneration in the
      medial meniscus. During diagnostic and surgical arthroscopy, rust-colored
      synovial hypertrophy was noted in the suprapatellar pouch accompanied by patchy
      villi and nodules and cystic changes. The gross appearance of the synovium
      mimicked that of pigmented villonodular synovitis. Biopsy specimens were obtained
      from different parts of the synovium and a subtotal synovectomy was performed.
      The histopathologic diagnosis was reported as hemosiderotic synovitis. During a
      three-year follow-up, she had no pain, snapping sensation, or limitation of
      motion. There were no recurrent effusions.

PMID- 20676021
TI  - Expanding nail or expanding femur? An adverse event with the expandable
      intramedullary nail.
AB  - The expandable intramedullary nail is self-locking and has the advantage of
      reducing operating time and exposure to ionizing radiation. The nail is
      recommended for simple diaphyseal fractures involving the middle third of long
      bones, where the nail can bypass the fracture site by at least 5 cm. We
      encountered a unique complication with the expandable nail in a simple transverse
      shaft fracture at the junction of the middle and distal third of the left femur
      in an otherwise healthy 57-year-old man. The fracture was reduced and a 12-mm
      expandable nail was inserted. Following full expansion, intraoperative
      radiographs were obtained prior to closure. After six postoperative weeks, it was
      noted that the nail expanded the femoral canal, converting a simple fracture to a
      distally progressing comminuted fracture with a butterfly fragment. A review of
      the intraoperative radiographs showed slight widening of the medullary canal at
      the level of the fracture. As the alignment was satisfactory and callus was
      present, no further surgical intervention was considered. The patient was advised
      not to bear weight and was provided with a locked knee brace in extension to wear
      for six weeks. Radiographs at 12 weeks demonstrated good progress of healing with
      adequate callus and the patient was permitted to bear weight as tolerated and
      commence knee flexion. The fracture united satisfactorily at four months. This
      adverse experience emphasizes that caution should be exercised when expanding the
      nail, with close observation of the medullary canal diameter during the later
      stages of expansion.

PMID- 20676022
TI  - Reverse floating first metatarsal and floating third metatarsal with Lisfranc
      fracture dislocation: an unusual injury.
AB  - A 25-year-old man complained of severe pain in the right foot after a traffic
      accident. There was a wound on the medial aspect of the foot extending over the
      length of the first metatarsal. There was no sign of vascular compromise and
      sensations were intact. Radiographs showed dislocation of the first
      tarsometatarsal (Lisfranc) and metatarsophalangeal joints with the head of the
      first metatarsal facing proximally and plantarward (reverse floating first
      metatarsal), a segmental fracture of the second metatarsal, fracture dislocation
      of the third metatarsal from the metatarsophalangeal and tarsometatarsal joints
      (floating third metatarsal), and fractures at the base of the fourth and fifth
      metatarsals and of cuneiforms. Open reduction and internal fixation were
      performed. The metatarsal head was buttonholed through the capsule and muscles
      and was released and reduced. The fractured second metatarsal was reduced and
      stabilized with a K-wire. The third floating metatarsal was aligned and fixed
      with a K-wire. A below-knee posterior plaster splint was applied for six weeks.
      Full weight bearing was started at 10 weeks. The patient returned to his
      activities with only minimal discomfort. This is the first reported case of
      plantar Lisfranc dislocation and reverse floating first metatarsal.

PMID- 20676023
TI  - Transglutaminase 2 inhibits apoptosis induced by calcium- overload through down
      regulation of Bax.
AB  - An abrupt increase of intracellular Ca(2+) is observed in cells under hypoxic or
      oxidatively stressed conditions. The dysregulated increase of cytosolic Ca(2+)
      triggers apoptotic cell death through mitochondrial swelling and activation of
      Ca(2+)-dependent enzymes. Transglutaminase 2 (TG2) is a Ca(2+)-dependent enzyme
      that catalyzes transamidation reaction producing cross-linked and polyaminated
      proteins. TG2 activity is known to be involved in the apoptotic process. However,
      the pro-apoptotic role of TG2 is still controversial. In this study, we
      investigate the role of TG2 in apoptosis induced by Ca(2+)-overload.
      Overexpression of TG2 inhibited the A23187-induced apoptosis through suppression
      of caspase-3 and -9 activities, cytochrome c release into cytosol, and
      mitochondria membrane depolarization. Conversely, down-regulation of TG2 caused
      the increases of cell death, caspase-3 activity and cytochrome c in cytosol in
      response to Ca(2+)-overload. Western blot analysis of Bcl-2 family proteins
      showed that TG2 reduced the expression level of Bax protein. Moreover,
      overexpression of Bax abrogated the anti-apoptotic effect of TG2, indicating that
      TG2-mediated suppression of Bax is responsible for inhibiting cell death under
      Ca(2+)-overloaded conditions. Our findings revealed a novel anti-apoptotic
      pathway involving TG2, and suggested the induction of TG2 as a novel strategy for
      promoting cell survival in diseases such as ischemia and neurodegeneration.

PMID- 20676024
TI  - Pathways of oncogene-induced senescence in human melanocytic cells.

PMID- 20676025
TI  - Regulation of vitamin metabolism by p53 and p63 in development and cancer.

PMID- 20676027
TI  - Angiogenic cells, macroparticles and RNA transcripts in laparoscopic vs open
      surgery for colorectal cancer.
AB  - BACKGROUND: Angiogenesis is crucial for tissue repair and cancer progression. We
      investigated a panel of angiogenic cells, macroparticles and RNA transcripts
      before, during and after laparoscopic colectomy or open colectomy for colorectal
      cancer. RESULTS: Viable and apoptotic circulating endothelial cells were
      significantly increased after open but not after laparoscopic colectomy (p <
      0.01). A significant decrease of circulating mRNA coding for VEGFR-C and D and
      PDGFR-beta was found after laparoscopic but not after open colectomy. METHODS: A
      total of 24 patients were enrolled. Viable and apoptotic circulating endothelial
      cells, progenitors and macroparticles were evaluated by flow cytometry. The
      number of copies of angiogenesis-related RNA transcripts we reevaluated by
      quantitative PCR. CONCLUSION: Open, but not laparoscopic colectomy, was
      associated with a significant post-operative increase in circulating endothelial
      cells, either apoptotic (likely due to surgery-related vascular damage) and
      viable (likely representing vascular remodeling). Circulating RNA copies coding
      for some angiogenic genes were significantly decreased after laparoscopic
      colectomy likely because of the removal of the tumor lesion. This decrease was
      not observed after open colectomy,were a more pronounced wave of angiogenesis
      related to wound healing was expected. These results indicate a relevant wave of
      angiogenesis-related cells and transcripts after open but not after laparoscopic
      colectomy.

PMID- 20676026
TI  - Multivalent epigenetic marks confer microenvironment-responsive epigenetic
      plasticity to ovarian cancer cells.
AB  - "Epigenetic plasticity" refers to the capability of mammalian cells to alter
      their differentiation status via chromatin remodeling-associated alterations in
      gene expression. While epigenetic plasticity has been best associated with
      lineage commitment of embryonic stem cells, recent studies have demonstrated
      chromatin remodeling even in terminally differentiated normal cells, and advanced
      stage melanoma and breast cancer cells, in context-dependent responses to
      alterations in their microenvironment. In the current study, we extend this
      attribute of epigenetic plasticity to aggressive ovarian cancer cells, by using
      an integrative approach to associate cellular phenotypes with chromatin
      modifications ("ChIP-chip") and mRNA and microRNA expression. While we identified
      numerous gene promoters possessing the well-known "bivalent mark" of
      H3K27me3/H3K4me2, we also report 14 distinct, lesser-known bi-, tri-, and
      tetravalent combinations of activating and repressive chromatin modifications, in
      platinum-resistant CP70 ovarian cancer cells. The vast majority (>90%) of all the
      histone marks studied localized to regions within 2000 bp of transcription start
      sites, supporting a role in gene regulation. Upon a simple alteration in the
      microenvironment, transition from two- to three-dimensional culture, an increase
      (17% to 38%) in repressive-only marked promoters was observed, concomitant with a
      decrease (31% to 21%) in multivalent (i.e., juxtaposed permissive and repressive
      histone marked) promoters. Like embryonic/tissue stem and other (non-ovarian)
      carcinoma cells, ovarian cancer cell epigenetic plasticity reflects an inherent
      transcriptional flexibility for context-responsive alterations in phenotype. It
      is possible that this plasticity could be therapeutically exploited for the
      management of this lethal gynecologic malignancy.

PMID- 20676028
TI  - Polycomb group proteins: New targets of anti-cancer therapy.

PMID- 20676029
TI  - HDAC inhibitors conquer Polycomb proteins.

PMID- 20676030
TI  - Kinases involved in Rec8 phosphorylation revealed.

PMID- 20676031
TI  - HDAC inhibitors repress the polycomb protein BMI1.

PMID- 20676032
TI  - DeltaNp73beta is oncogenic in hepatocellular carcinoma by blocking apoptosis
      signaling via death receptors and mitochondria.

PMID- 20676034
TI  - A novel neuronal differentiation mechanism in which Slug and Escargot are major
      players.

PMID- 20676033
TI  - New functions for the Snail family of transcription factors: Two-faced proteins.

PMID- 20676035
TI  - Dancing with p53: The role of p38MAPK in mitosis of p53-deficient tetraploid
      cells.

PMID- 20676036
TI  - Properties of a general PK/PD model of antibody-ligand interactions for
      therapeutic antibodies that bind to soluble endogenous targets.
AB  - Antibodies that target endogenous soluble ligands are an important class of
      biotherapeutic agents. While much focus has been placed on characterization of
      antibody pharmacokinetics, less emphasis has been given to characterization of
      antibody effects on their soluble targets. We describe here the properties of a
      generalized mechanism-based PK/PD model used to characterize the in vivo
      interaction of an antibody and an endogenous soluble ligand. The assumptions and
      properties of the model are explored, and situations are described when
      deviations from the basic assumptions may be necessary. This model is most useful
      for in vivo situations where both antibody and ligand levels are available
      following drug administration. For a given antibody exposure, the extent and
      duration of suppression of free ligand is impacted by the apparent affinity of
      the interaction, as well as by the rate of ligand turnover. The applicability of
      the general equilibrium model of in vivo antibody-ligand interaction is
      demonstrated with an anti-Abeta antibody.

PMID- 20676037
TI  - A new role for microRNA-9 in human neural progenitor cells.

PMID- 20676038
TI  - Ionizing radiation and hematopoietic malignancies: altering the adaptive
      landscape.
AB  - Somatic evolution, which underlies tumor progression, is driven by two essential
      components: (1) diversification of phenotypes through heritable mutations and
      epigenetic changes and (2) selection for mutant clones which possess higher
      fitness. Exposure to ionizing radiation (IR ) is highly associated with increased
      risk of carcinogenesis. This link is traditionally attributed to causation of
      oncogenic mutations through the mutagenic effects of irradiation. On the other
      hand, potential effects of irradiation on altering fitness and increasing
      selection for mutant clones are frequently ignored. Recent studies bring the
      effects of irradiation on fitness and selection into focus, demonstrating that IR
      exposure results in stable reductions in the fitness of hematopoietic stem and
      progenitor cell populations. These reductions of fitness are associated with
      alteration of the adaptive landscape, increasing the selective advantages
      conferred by certain oncogenic mutations. Therefore, the link between irradiation
      and carcinogenesis might be more complex than traditionally appreciated: while
      mutagenic effects of irradiation should increase the probability of occurrence of
      oncogenic mutations, IR can also work as a tumor promoter, increasing the
      selective expansion of clones bearing mutations which become advantageous in the
      irradiation-altered environment, such as activated mutations in Notch1 or
      disrupting mutations in p53.

PMID- 20676039
TI  - Dasatinib alters the metastatic phenotype of B16-OVA melanoma in vivo.
AB  - The Src/Abl tyrosine kinase inhibitor dasatinib is an approved chronic myeloid
      leukemia treatment and is under investigation for solid tumor therapy. Members of
      the Src family of kinases (SFKs) are involved in the process of metastasis and
      dasatinib inhibits the migration and invasiveness of human melanoma cell lines in
      vitro. SFKs are also involved in immune function and angiogenesis, which both
      contribute to As active and passive immunotherapies continue to be investigated
      in metastatic melanoma, we investigated possible interactions between kinase
      inhibitors and immunotherapies. A murine syngenic model of metastatic melanoma in
      which B16F10 cells expressed ovalbumin (B16-OVA) was employed and the active
      immunotherapy comprised immunization with an OVA-expressing recombinant fowlpox
      virus (FPVOVA).Dasatinib did not affect B16-OVA viability, proliferation,
      migration or soft agar colony formation. However, depending on drug dose and
      schedule, differences in the metastatic behavior of B16-OVA were observed in vivo
      after dasatinib therapy. At a dose of 5 mg/kg/day given before tumor challenge,
      dasatinib therapy reduced the number of pulmonary metastases. Conversely, a
      higher dose (25 mg/kg/day), did not affect the number of pulmonary metastases and
      increased the number of extra-pulmonary metastases. Finally, immunization of B16
      OVA-bearing mice with FPVOVA reduced the number of lung metastases. Prior
      treatment of these mice with dasatinib 5 mg/kg/day did not affect the incidence
      of lung metastases. Although the mechanisms by which dasatinib alters the
      metastatic behavior of B16-OVA cells in vivo remain to be determined, we
      hypothesize that dasatinib acts via multiple tumor-extrinsic processes that
      include immune function and neoangiogenesis.

PMID- 20676040
TI  - Signaling pathways in the epithelial origins of pulmonary fibrosis.
AB  - Pulmonary fibrosis complicates a number of disease processes and leads to
      substantial morbidity and mortality. Idiopathic pulmonary fibrosis (IPF) is
      perhaps the most pernicious and enigmatic form of the greater problem of lung
      fibrogenesis with a median survival of three years from diagnosis in affected
      patients. In this review, we will focus on the pathology of IPF as a model of
      pulmonary fibrotic processes, review possible cellular mechanisms, review current
      treatment approaches and review two transgenic mouse models of lung fibrosis to
      provide insight into processes that cause lung fibrosis. We will also summarize
      the potential utility of signaling pathway inhibitors as a future treatment in
      pulmonary fibrosis. Finally, we will present data demonstrating a minimal
      contribution of epithelial-mesenchymal transition in the development of fibrotic
      lesions in the transforming growth factor-alpha transgenic model of lung
      fibrosis.

PMID- 20676042
TI  - The discovery of a Werner Helicase Interacting Protein (WHIP) association with
      the nuclear pore complex.
AB  - The gateway for molecular trafficking between the cytoplasm and the nucleus is
      the Nuclear Pore Complex (NPC). Through mass spectral analysis of the isolated
      Nuclear Pore Nup107-160 subcomplex, we discovered an in vivo interaction with
      Werner's Helicase Interacting Protein 1, (WRNIP1 or WHIP). WHIP was originally
      identified as a binding partner of Werner protein (WRN), which functions to
      maintain genome stability and is responsible for the progeria disease, Werner
      syndrome. We established the reciprocal isolation of Nup107 by alpha-WHIP. WHIP
      was found in purified Nuclear Envelope (NE) fractions treated with
      DNase/RNase/Heparin. We demonstrated by immunofluorescence microscopy that WHIP
      is located at the nuclear rim as well as punctate regions in the nuclear matrix.
      Ultimately, synchronized cells show a dynamic association between WHIP and the
      Nup107-160 subcomplex through the cell cycle without an interaction with WRN. We
      thus identify WHIP as a partner/component of the NE/NPC and set forth to
      investigate a role for the protein positioned at the NPC.

PMID- 20676041
TI  - Characterization of a novel mutation in the cardiac ryanodine receptor that
      results in catecholaminergic polymorphic ventricular tachycardia.
AB  - Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an arrhythmogenic
      disease that manifests as syncope or sudden death during high adrenergic tone in
      the absence of structural heart defects. It is primarily caused by mutations in
      the cardiac ryanodine receptor (RyR2). The mechanism by which these mutations
      cause arrhythmia remains controversial, with discrepant findings related to the
      role of the RyR2 binding protein FKBP12.6. The purpose of this study was to
      characterize a novel RyR2 mutation identified in a kindred with clinically
      diagnosed CPVT. Single-strand conformational polymorphism analysis and direct DNA
      sequencing were used to screen the RyR2 gene for mutations. Site-directed
      mutagenesis was employed to introduce the mutation into the mouse RyR2 cDNA. The
      impact of the mutation on the interaction between RyR2 and a 12.6 kDa FK506
      binding protein (FKBP12.6) was determined by immunoprecipitation and
      immunoblotting and its effect on RyR2 function was characterized by single cell
      Ca(2+) imaging and [(3)H]ryanodine binding. A novel CPVT mutation, E189D, was
      identified. The E189D mutation does not alter the affinity of the channel for
      FKBP12.6, but it increases the propensity for store-overload-induced Ca(2+)
      release (SOICR). Furthermore, the E189D mutation enhances the basal channel
      activity of RyR2 and its sensitivity to activation by caffeine. The E189D RyR2
      mutation is causative for CPVT and functionally increases the propensity for
      SOICR without altering the affinity for FKBP12.6. These observations strengthen
      the notion that enhanced SOICR, but not altered FKBP12.6 binding, is a common
      mechanism by which RyR2 mutations cause arrhythmias.

PMID- 20676043
TI  - ERBB3: Multifunctional enabler or primary actor in pancreatic cancer?

PMID- 20676044
TI  - Loss of inhibitory insulin receptor substrate-1 phosphorylation: An early event
      in endometrial hyperplasia and progression to carcinoma.

PMID- 20676045
TI  - Differential control of ATGL-mediated lipid droplet degradation by CGI-58 and
      G0S2.
AB  - Lipid droplets (LDs) are intracellular storage sites for triacylglyerols
      (TAGs)and steryl esters, and play essential roles in energy metabolism and
      membrane biosynthesis. Adipose triglyceride lipase (ATGL) is the key enzyme for
      TAG hydrolysis (lipolysis) in adipocytes and LD degradation in nonadipocyte
      cells. Lipase activity of ATGL in vivo largely depends on its C-terminal sequence
      as well as coactivation by CGI-58. Here we demonstrate that the C-terminal
      hydrophobic domain in ATGL is required for LD targeting and CGI-58-independent LD
      degradation. Overexpression of wild type ATGL causes a dramatic decrease in LD
      size and number, whereas a mutant lacking the hydrophobic domain fails to
      localize to LDs and to affect their morphology. Interestingly, coexpression of
      CGI-58 is able to promote LD turnover mediated by this ATGL mutant. Recently we
      have discovered that G0S2 acts as an inhibitor of ATGL activity and ATGL-mediated
      lipolysis. Here we show that G0S2 binds to ATGL irrelevantly of its activity
      state or the presence of CGI-58. In G0S2-expressing cells, the combined
      expression of CGI-58 and ATGL is incapable of stimulating LD turnover. We propose
      that CGI-58 and G0S2 regulate ATGL via non-competing mechanisms.

PMID- 20676046
TI  - tRNA and cytochrome c in cell death and beyond.
AB  - Both transfer RNA (tRNA) and cytochrome c are essential to cellular function:
      tRNA mediates protein synthesis while cytochrome c is required for oxidative
      phosphorylation and apoptosis induction. tRNA has recently been implicated as a
      direct regulator of the well-conserved apoptotic role of cytochrome c.
      Interaction between these molecules could potentially coordinate biosynthesis,
      energy production and apoptosis. Here we review the diversity and dynamics of
      tRNA and how this class of non-coding RNAs may regulate the role of cytochrome c
      in apoptosis. We comment on unanswered questions in the cell biology of this
      interaction and how answers may influence our understanding of disease.

PMID- 20676048
TI  - The 20th ion channel meeting: September 2009, France.
AB  - The French Ion Channel society has existed since 1989 and its main goal is to
      annually organize a scientific meeting. This meeting, which gathers young and
      senior French scientists, provides a great opportunity for exchange and
      interaction among the ion channel research community. Additionally, for many
      years, the French ion channel meeting has attracted a significant number of
      scientists from different European countries, promoting the discussion of new
      insights and advances, as well as aiding in the establishment of collaborations.
      In this report, we summarize the five symposia selected for their novelty and
      importance in human channelopathies, neuroplasticity, ion channel regulations,
      intracellular ion channels and plant physiology.

PMID- 20676047
TI  - Oligomerization of the voltage-gated proton channel.
AB  - The voltage-gated proton channel exists as a dimer, although each protomer has a
      separate conduction pathway, and when forced to exist as a monomer, most major
      functions are retained. However, the proton channel protomers appear to interact
      during gating. Proton channel dimerization is thought to result mainly from
      coiled-coil interaction of the intracellular C-termini. Several types of evidence
      are discussed that suggest that the dimer conformation may not be static, but is
      dynamic and can sample different orientations. Zn(2+) appears to link the
      protomers in an orientation from which the channel(s) cannot open. A tandem WT-WT
      dimer exhibits signs of cooperative gating, indicating that despite the abnormal
      linkage, the correct orientation for opening can occur. We propose that C
      terminal interaction functions mainly to tether the protomers together.
      Comparison of the properties of monomeric and dimeric proton channels speaks
      against the hypothesis that enhanced gating reflects monomer-dimer
      interconversion.

PMID- 20676049
TI  - Loss of ATM positively regulates the expression of hypoxia inducible factor 1
      (HIF-1) through oxidative stress: Role in the physiopathology of the disease.
AB  - Ataxia Telangiectasia (AT) is an autosomal recessive disorder characterized by a
      wide variety of progressive clinical symptoms. This includes neuronal
      degeneration, oculocutaneous telangiectasias, diabetes mellitus,
      immunodeficiency, increased risk of cancer and sensitivity to ionizing radiation.
      The gene mutated in this disease, ATM (Ataxia Telangiectasia Mutated), encodes a
      protein kinase involved in DNA double strand breaks signalling and repair. ATM
      deficient cells also display an increase in oxidative stress, by poorly
      characterized mechanism(s), which clearly contributes to the neurodegenerative
      aspect of the disease. Despite these advances, the occurrence of the vascular
      abnormalities, glucose intolerance and insulin resistance remains poorly
      understood. In different cellular models where ATM expression was disrupted, we
      demonstrated that the absence of ATM leads to an increased expression of both
      subunits of the transcription factor Hypoxia Inducible Factor 1 (HIF-1). We also
      observed enhanced trans-activating functions of HIF-1. HIF-1 is the central
      regulator of responses to hypoxia which induces the transcription of genes
      involved in angiogenesis (e.g., VEGF-Vascular Endothelial Growth Factor) and
      cellular metabolism (e.g., GLUT-1). Interestingly, we demonstrated that ATM
      disruption positively regulates both expression and function of the basal glucose
      transporter GLUT-1 as well as the proangiogenic factor, VEGF. In addition, our
      results suggest that the absence of ATM increases HIF-1 proteins biosynthesis,
      and this effect is dependant on the oxidative stress existing in ATM deficient
      cells. Our compelling results highlight a new link between ATM deficiency and the
      clinical features of the disease and provide a molecular link between ATM
      downregulation and the increase in tumor angiogenesis observed in human breast
      cancers.

PMID- 20676050
TI  - FM19G11: A new modulator of HIF that links mTOR activation with the DNA damage
      checkpoint pathways.
AB  - The network consisting of mTOR and p53 pathways is crucial to understanding a
      wide variety of physiological and pathological events, including cancer and
      aging. In addition, the HIF1alpha protein, a downstream target of mTOR, is a
      hallmark of different tumor types and was the desired strategy of many drug
      discovery efforts. Here we present the novel chemical entity FM19G11, a new
      modulator of HIF1alpha expression, which was used as a molecular tool to dissect
      and further characterize the cross-talk between these signaling cascades in human
      colon carcinoma cell lines. To our knowledge, FM19G11 is the first drug that
      triggers a DNA damage response (DDR) associated with G(1)/S-phase arrest in a p53
      dependent manner, due to rapid hyper-activation of the growth signaling pathway
      through mTOR. Assessment of colonies demonstrated that FM19G11 decreases the
      clonogenicity of HT29, HCT116/p53(+/+) and HCT116/p53(-/-) cells. Moreover,
      FM19G11 causes significant lower colony growth in soft agar of p53-proficient
      human colon cancer cells. Consequently, p53 sensitizes human colon cancer cells
      to FM19G11 by significant reduction of their viability, lessening their colony
      formation capability and shrinking their anchorage-independent growth. Cell
      signaling studies served to assign a new mode of action to FM19G11, whose tumor
      suppressant activity compromises the survival of functional p53 malignant cells.

PMID- 20676051
TI  - MAD2 downregulation in hypoxia is independent of promoter hypermethylation.
AB  - Aberrant expression of the MAD2 protein has been linked to chromosomal
      instability, malignant transformation and chemoresistance. Although reduced MAD2
      expression is well recognised in human cancer cell lines, the mechanism(s)
      underlying its downregulation remain elusive. The objective of this study was to
      establish the impact of hypoxia on MAD2 expression and to investigate the
      potential role of aberrant promoter methylation as a possible mechanism of MAD2
      downregulation. For this purpose, three ovarian cancer cell lines, displaying
      differing levels of MAD2, were treated with chromatin modifying drugs, pre and
      post-hypoxia exposure and a DHPLC analysis of DNA promoter methylation carried
      out. We show that hypoxia induces downregulation of MAD2 expression,
      independently of MAD2 promoter methylation. We also show no evidence of MAD2
      promoter methylation in breast and prostate cancer cells or in breast cancer
      clinical material. While our findings provide no evidence for MAD2 promoter
      methylation, we show a concomitant upregulation of p21 with downregulation of
      MAD2 in hypoxia. Our in vitro results were also confirmed in an ovarian cancer
      tissue microarray (TMA), where a reciprocal staining of MAD2 and CAIX was found
      in 21/60 (35%) of tumours. In summary, MAD2 downregulation may be a crucial
      mechanism by which hypoxic cells become chemorefractory. This stems from our
      previous work where we demonstrated that MAD2 downregulation induces cellular
      senescence, a viable cellular fate, with resultant cellular resistance to
      paclitaxel. Moreover, MAD2 downregulation could play a central role in the
      induction of chemoresistance in hypoxia, a key tumour microenvironment associated
      with chemoresistance.

PMID- 20676052
TI  - TRPV4-mediated channelopathies.
AB  - Transient receptor potential vanilloid sub type 4 (TRPV4) is a member of non
      selective cation channel that is important for sensation of several physical and
      chemical stimuli and also involved in multiple physiological functions. Recently
      it gained immense medical and clinical interest as several independent studies
      have demonstrated that mutations in the TRPV4 gene can results in genetic
      disorders like Brachyolmia, Charcot-Marie-Tooth disease type 2C, Spinal Muscular
      Atrophy and Hereditary Motor and Sensory Neuropathy type 2. Close analysis of the
      data obtained from these naturally occurring as well as other TRPV4 mutants
      suggest that it is not the altered channel activity of these mutants per se, but
      the involvement and interaction of other factors that seem to modulate
      oligomerization, trafficking and degradation of TRPV4 channels. Also, these
      factors can either enhance or reduce the activity of TRPV4. In addition, there
      are some potential signaling events that can also be involved in these genetic
      disorders. In this review, we analyzed how and what extent certain cellular and
      molecular functions like oligomerization, surface expression, ubiquitination and
      functional interactions might be affected by these mutations.

PMID- 20676053
TI  - The future of monoclonal antibody technology.
AB  - With the rapid growth of monoclonal antibody-based products, new technologies
      have emerged for creating modified forms of antibodies, including fragments,
      conjugates and multi-specific antibodies. We created a database of 450
      therapeutic antibodies in development to determine which technologies and
      indications will constitute the "next generation" of antibody products. We
      conclude that the antibodies of the future will closely resemble the antibodies
      that have already been approved for commercial sale. 

PMID- 20676054
TI  - Stimulants in bipolar disorder: beyond common beliefs.

PMID- 20676055
TI  - Varenicline-induced Psychosis.

PMID- 20676056
TI  - ADAM10 is the physiologically relevant, constitutive alpha-secretase of the
      amyloid precursor protein in primary neurons.
AB  - The amyloid precursor protein (APP) undergoes constitutive shedding by a protease
      activity called alpha-secretase. This is considered an important mechanism
      preventing the generation of the Alzheimer's disease amyloid-beta peptide
      (Abeta). alpha-Secretase appears to be a metalloprotease of the ADAM family, but
      its identity remains to be established. Using a novel alpha-secretase-cleavage
      site-specific antibody, we found that RNAi-mediated knockdown of ADAM10, but
      surprisingly not of ADAM9 or 17, completely suppressed APP alpha-secretase
      cleavage in different cell lines and in primary murine neurons. Other proteases
      were not able to compensate for this loss of alpha-cleavage. This finding was
      further confirmed by mass-spectrometric detection of APP-cleavage fragments.
      Surprisingly, in different cell lines, the reduction of alpha-secretase cleavage
      was not paralleled by a corresponding increase in the Abeta-generating beta
      secretase cleavage, revealing that both proteases do not always compete for APP
      as a substrate. Instead, our data suggest a novel pathway for APP processing, in
      which ADAM10 can partially compete with gamma-secretase for the cleavage of a C
      terminal APP fragment generated by beta-secretase. We conclude that ADAM10 is the
      physiologically relevant, constitutive alpha-secretase of APP.

PMID- 20676057
TI  - The key function of a conserved and modified rRNA residue in the ribosomal
      response to the nascent peptide.
AB  - The ribosome is able to monitor the structure of the nascent peptide and can
      stall in response to specific peptide sequences. Such programmed stalling is used
      for the regulation of gene expression. The molecular mechanisms of the nascent
      peptide recognition and ribosome stalling are unknown. We identified the
      conserved and posttranscriptionally modified 23S rRNA nucleotide m(2)A2503
      located at the entrance of the ribosome exit tunnel as a key component of the
      ribosomal response mechanism. A2503 mutations abolish nascent-peptide-dependent
      stalling at the leader cistrons of several inducible antibiotic resistance genes
      and at the secM regulatory gene. Remarkably, lack of the C2 methylation of A2503
      significantly function induction of expression of the ermC gene, indicating that
      the functional role of posttranscriptional modification is to fine-tune ribosome
      nascent peptide interactions. Structural and biochemical evidence suggest that
      m(2)A2503 may act in concert with the previously identified nascent-peptide
      sensor, A2062, in the ribosome exit tunnel to relay the stalling signal to the
      peptidyl transferase centre.

PMID- 20676058
TI  - Oncogenesis by sequestration of CBP/p300 in transcriptionally inactive
      hyperacetylated chromatin domains.
AB  - In a subset of poorly differentiated and highly aggressive carcinoma, a
      chromosomal translocation, t(15;19)(q13;p13), results in an in-frame fusion of
      the double bromodomain protein, BRD4, with a testis-specific protein of unknown
      function, NUT (nuclear protein in testis). In this study, we show that, after
      binding to acetylated chromatin through BRD4 bromodomains, the NUT moiety of the
      fusion protein strongly interacts with and recruits p300, stimulates its
      catalytic activity, initiating cycles of BRD4-NUT/p300 recruitment and creating
      transcriptionally inactive hyperacetylated chromatin domains. Using a patient
      derived cell line, we show that p300 sequestration into the BRD4-NUT foci is the
      principal oncogenic mechanism leading to p53 inactivation. Knockdown of BRD4-NUT
      released p300 and restored p53-dependent regulatory mechanisms leading to cell
      differentiation and apoptosis. This study demonstrates how the off-context
      activity of a testis-specific factor could markedly alter vital cellular
      functions and significantly contribute to malignant cell transformation.

PMID- 20676059
TI  - Zic2 regulates the expression of Sert to modulate eye-specific refinement at the
      visual targets.
AB  - The development of the nervous system is a time-ordered and multi-stepped process
      that requires neural specification, axonal navigation and arbor refinement at the
      target tissues. Previous studies have demonstrated that the transcription factor
      Zic2 is necessary and sufficient for the specification of retinal ganglion cells
      (RGCs) that project ipsilaterally at the optic chiasm midline. Here, we report
      that, in addition, Zic2 controls the refinement of eye-specific inputs in the
      visual targets by regulating directly the expression of the serotonin transporter
      (Sert), which is involved in the modulation of activity-dependent mechanisms
      during the wiring of sensory circuits. In agreement with these findings, RGCs
      that express Zic2 ectopically show defects in axonal refinement at the visual
      targets and respond to pharmacological blockage of Sert, whereas Zic2-negative
      contralateral RGCs do not. These results link, at the molecular level, early
      events in neural differentiation with late activity-dependent processes and
      propose a mechanism for the establishment of eye-specific domains at the visual
      targets.

PMID- 20676060
TI  - An MEK-cofilin signalling module controls migration of human T cells in 3D but
      not 2D environments.
AB  - T cells infiltrate peripheral tissues to execute immunosurveillance and effector
      functions. For this purpose, T cells first migrate on the two-dimensional (2D)
      surface of endothelial cells to undergo transendothelial migration. Then they
      change their mode of movement to undergo migration within the three-dimensional
      (3D)-extracellular matrix of the infiltrated tissue. As yet, no molecular
      mechanisms are known, which control migration exclusively in either 2D or 3D
      environments. Here, we describe a signalling module that controls T-cell
      chemotaxis specifically in 3D environments. In chemotaxing T cells, Ras activity
      is spatially restricted to the lamellipodium. There, Ras initiates activation of
      MEK, which in turn inhibits LIM-kinase 1 activity, thereby allowing
      dephosphorylation of the F-actin-remodelling protein cofilin. Interference with
      this MEK-cofilin module by either inhibition of MEK or by knockdown of cofilin
      reduces speed and directionality of chemotactic migration in 3D-extracellular
      matrices, but not on 2D substrates. This MEK-cofilin module may have an important
      function in the tissue positioning of T cells during an immune response.

PMID- 20676061
TI  - Unique microRNA profile in Dupuytren's contracture supports deregulation of beta
      catenin pathway.
AB  - Dupuytren's contracture, a proliferative disease of unknown origin, is
      characterized by an abnormal fibroblast proliferation process. Evidence from
      numerous microRNA (miRNA) studies shows that miRNAs have a vital function in many
      biological processes, for instance, in cellular signaling networks, cell growth,
      tissue differentiation, and cell proliferation. Our aim was to characterize, to
      our knowledge for the first time, the miRNA-expression profile of Dupuytren's
      contracture. The miRNAs identified may have a function in the pathogenesis of
      Dupuytren's contracture by targeting and regulating important pathways. We
      compared the miRNA-expression profile of 29 Dupuytren's contracture patients with
      that of control samples (fibroblast cells and palmar fascia). Some of the miRNAs
      identified in our Dupuytren's contracture samples, including miR-29c, miR-130b,
      miR-101, miR-30b, and miR-140-3p, were found to regulate important genes related
      to the beta-catenin pathway: WNT5A, ZIC1, and TGFB1. Expression profiles of these
      genes reanalyzed from published gene-expression data from similar patient
      material correlated with our miRNA results. Analysis was also performed for
      groups of patients with recurrent/non-recurrent and patients with hereditary/non
      hereditary Dupuytren's contracture, but no significant differences appeared in
      miRNA-expression profiles of these groups. Identification of unique miRNA
      expression in Dupuytren's contracture may lead to the development of novel
      molecular therapy for its treatment.

PMID- 20676062
TI  - Clinical outcome in diagnostically ambiguous foci of 'gland crowding' in the
      endometrium.
AB  - Premalignant endometrial lesions (endometrial intraepithelial neoplasia (EIN))
      are clonal neoplasms that arise focally and can be diagnosed using specific
      criteria: (1) area of glands exceeds that of stroma (glands/stroma >1), (2)
      nuclear and/or cytoplasmic features of epithelial cells differ between
      architecturally abnormal glands and normal background glands, and (3) maximum
      linear dimension exceeds 1 mm. However, localized groups of crowded endometrial
      glands may be encountered that do not fulfill all of the criteria for EIN, are
      interpreted as ambiguous, and are reported as 'focal gland crowding'. We
      conducted a retrospective study of gland crowding using a free-text index search
      for this term in our pathology files. The age of the patients, number of
      subsequent specimens, the duration, and the outcome of the follow-ups were
      recorded. Of the 71,579 consecutive gynecological pathology reports, 206 (0.3%)
      'gland crowding' cases were identified, in which 69% (143/206) had follow-up
      sampling. Of these, 33 (23%) had an outcome diagnosis of EIN (27 cases; 19%) or
      carcinoma (6 cases; 4%). Included were 18 cases (55%) diagnosed within the first
      year and presumed concurrent, and an additional 15 (45%) discovered after 1 year
      and interpreted as a later phase of disease or new events. The term 'crowded
      glands' is a highly significant finding that carries a substantial risk of an
      outcome of EIN and occasionally malignancy. It underscores the importance of
      follow-up when some but not all of the criteria for EIN are encountered in the
      appropriate clinical setting.

PMID- 20676063
TI  - Of genomics and bioinformatics.

PMID- 20676065
TI  - Comparison of performance of one-color and two-color gene-expression analyses in
      predicting clinical endpoints of neuroblastoma patients.
AB  - Microarray-based prediction of clinical endpoints may be performed using either a
      one-color approach reflecting mRNA abundance in absolute intensity values or a
      two-color approach yielding ratios of fluorescent intensities. In this study, as
      part of the MAQC-II project, we systematically compared the classification
      performance resulting from one- and two-color gene-expression profiles of 478
      neuroblastoma samples. In total, 196 classification models were applied to these
      measurements to predict four clinical endpoints, and classification performances
      were compared in terms of accuracy, area under the curve, Matthews correlation
      coefficient and root mean-squared error. Whereas prediction performance varied
      with distinct clinical endpoints and classification models, equivalent
      performance metrics were observed for one- and two-color measurements in both
      internal and external validation. Furthermore, overlap of selected signature
      genes correlated inversely with endpoint prediction difficulty. In summary, our
      data strongly substantiate that the choice of platform is not a primary factor
      for successful gene expression based-prediction of clinical endpoints.

PMID- 20676064
TI  - Consistency of predictive signature genes and classifiers generated using
      different microarray platforms.
AB  - Microarray-based classifiers and associated signature genes generated from
      various platforms are abundantly reported in the literature; however, the utility
      of the classifiers and signature genes in cross-platform prediction applications
      remains largely uncertain. As part of the MicroArray Quality Control Phase II
      (MAQC-II) project, we show in this study 80-90% cross-platform prediction
      consistency using a large toxicogenomics data set by illustrating that: (1) the
      signature genes of a classifier generated from one platform can be directly
      applied to another platform to develop a predictive classifier; (2) a classifier
      developed using data generated from one platform can accurately predict samples
      that were profiled using a different platform. The results suggest the potential
      utility of using published signature genes in cross-platform applications and the
      possible adoption of the published classifiers for a variety of applications. The
      study reveals an opportunity for possible translation of biomarkers identified
      using microarrays to clinically validated non-array gene expression assays.

PMID- 20676066
TI  - Genomic indicators in the blood predict drug-induced liver injury.
AB  - Genomic biomarkers for the detection of drug-induced liver injury (DILI) from
      blood are urgently needed for monitoring drug safety. We used a unique data set
      as part of the Food and Drug Administration led MicroArray Quality Control Phase
      II (MAQC-II) project consisting of gene expression data from the two tissues
      (blood and liver) to test cross-tissue predictability of genomic indicators to a
      form of chemically induced liver injury. We then use the genomic indicators from
      the blood as biomarkers for prediction of acetaminophen-induced liver injury and
      show that the cross-tissue predictability of a response to the pharmaceutical
      agent (accuracy as high as 92.1%) is better than, or at least comparable to, that
      of non-therapeutic compounds. We provide a database of gene expression for the
      highly informative predictors, which brings biological context to the possible
      mechanisms involved in DILI. Pathway-based predictors were associated with
      inflammation, angiogenesis, Toll-like receptor signaling, apoptosis, and
      mitochondrial damage. The results show for the first time and support the
      hypothesis that genomic indicators in the blood can serve as potential diagnostic
      biomarkers predictive of DILI.

PMID- 20676067
TI  - A comparison of batch effect removal methods for enhancement of prediction
      performance using MAQC-II microarray gene expression data.
AB  - Batch effects are the systematic non-biological differences between batches
      (groups) of samples in microarray experiments due to various causes such as
      differences in sample preparation and hybridization protocols. Previous work
      focused mainly on the development of methods for effective batch effects removal.
      However, their impact on cross-batch prediction performance, which is one of the
      most important goals in microarray-based applications, has not been addressed.
      This paper uses a broad selection of data sets from the Microarray Quality
      Control Phase II (MAQC-II) effort, generated on three microarray platforms with
      different causes of batch effects to assess the efficacy of their removal. Two
      data sets from cross-tissue and cross-platform experiments are also included. Of
      the 120 cases studied using Support vector machines (SVM) and K nearest neighbors
      (KNN) as classifiers and Matthews correlation coefficient (MCC) as performance
      metric, we find that Ratio-G, Ratio-A, EJLR, mean-centering and standardization
      methods perform better or equivalent to no batch effect removal in 89, 85, 83, 79
      and 75% of the cases, respectively, suggesting that the application of these
      methods is generally advisable and ratio-based methods are preferred.

PMID- 20676068
TI  - k-Nearest neighbor models for microarray gene expression analysis and clinical
      outcome prediction.
AB  - In the clinical application of genomic data analysis and modeling, a number of
      factors contribute to the performance of disease classification and clinical
      outcome prediction. This study focuses on the k-nearest neighbor (KNN) modeling
      strategy and its clinical use. Although KNN is simple and clinically appealing,
      large performance variations were found among experienced data analysis teams in
      the MicroArray Quality Control Phase II (MAQC-II) project. For clinical end
      points and controls from breast cancer, neuroblastoma and multiple myeloma, we
      systematically generated 463,320 KNN models by varying feature ranking method,
      number of features, distance metric, number of neighbors, vote weighting and
      decision threshold. We identified factors that contribute to the MAQC-II project
      performance variation, and validated a KNN data analysis protocol using a newly
      generated clinical data set with 478 neuroblastoma patients. We interpreted the
      biological and practical significance of the derived KNN models, and compared
      their performance with existing clinical factors.

PMID- 20676069
TI  - Functional analysis of multiple genomic signatures demonstrates that
      classification algorithms choose phenotype-related genes.
AB  - Gene expression signatures of toxicity and clinical response benefit both safety
      assessment and clinical practice; however, difficulties in connecting signature
      genes with the predicted end points have limited their application. The
      Microarray Quality Control Consortium II (MAQCII) project generated 262
      signatures for ten clinical and three toxicological end points from six gene
      expression data sets, an unprecedented collection of diverse signatures that has
      permitted a wide-ranging analysis on the nature of such predictive models. A
      comprehensive analysis of the genes of these signatures and their nonredundant
      unions using ontology enrichment, biological network building and interactome
      connectivity analyses demonstrated the link between gene signatures and the
      biological basis of their predictive power. Different signatures for a given end
      point were more similar at the level of biological properties and transcriptional
      control than at the gene level. Signatures tended to be enriched in function and
      pathway in an end point and model-specific manner, and showed a topological bias
      for incoming interactions. Importantly, the level of biological similarity
      between different signatures for a given end point correlated positively with the
      accuracy of the signature predictions. These findings will aid the understanding,
      and application of predictive genomic signatures, and support their broader
      application in predictive medicine.

PMID- 20676070
TI  - Variability in GWAS analysis: the impact of genotype calling algorithm
      inconsistencies.
AB  - The Genome-Wide Association Working Group (GWAWG) is part of a large-scale effort
      by the MicroArray Quality Consortium (MAQC) to assess the quality of genomic
      experiments, technologies and analyses for genome-wide association studies
      (GWASs). One of the aims of the working group is to assess the variability of
      genotype calls within and between different genotype calling algorithms using
      data for coronary artery disease from the Wellcome Trust Case Control Consortium
      (WTCCC) and the University of Ottawa Heart Institute. Our results show that the
      choice of genotyping algorithm (for example, Bayesian robust linear model with
      Mahalanobis distance classifier (BRLMM), the corrected robust linear model with
      maximum-likelihood-based distances (CRLMM) and CHIAMO (developed and implemented
      by the WTCCC)) can introduce marked variability in the results of downstream case
      control association analysis for the Affymetrix 500K array. The amount of
      discordance between results is influenced by how samples are combined and
      processed through the respective genotype calling algorithm, indicating that
      systematic genotype errors due to computational batch effects are propagated to
      the list of single-nucleotide polymorphisms found to be significantly associated
      with the trait of interest. Further work using HapMap samples shows that
      inconsistencies between Affymetrix arrays and calling algorithms can lead to
      genotyping errors that influence downstream analysis.

PMID- 20676071
TI  - Batch effects in the BRLMM genotype calling algorithm influence GWAS results for
      the Affymetrix 500K array.
AB  - The Affymetrix GeneChip Human Mapping 500K array is common for genome-wide
      association studies (GWASs). Recent findings highlight the importance of accurate
      genotype calling algorithms to reduce the inflation in Type I and Type II error
      rates. Differential results due to genotype calling errors can introduce severe
      bias in case-control association study results. Using data from the Wellcome
      Trust Case Control Consortium, 1991 individuals with coronary artery disease
      (CAD) and 1500 controls from the UK Blood Services (NBS) were genotyped on the
      Affymetrix 500K array. Different batch sizes and compositions were used in the
      Bayesian Robust Linear Model with Mahalanobis distance classifier (BRLMM)
      genotype calling algorithm to assess the batch effect on downstream association
      analysis. Results show that composition (cases and controls genotyped
      simultaneously or separate) and size (number of individuals processed by BRLMM at
      a time) can create 2-3% discordance in the results for quality control and
      statistical analysis and may contribute to the lack of reproducibility between
      GWASs. The changes in batch size are largely responsible for differential single
      nucleotide polymorphism results, yet we observe evidence of an interactive effect
      of batch size and composition that contributes to discordant results in the list
      of significantly associated loci.

PMID- 20676072
TI  - Assessment of variability in GWAS with CRLMM genotyping algorithm on WTCCC
      coronary artery disease.
AB  - The robustness of genome-wide association study (GWAS) results depends on the
      genotyping algorithms used to establish the association. This paper initiated the
      assessment of the impact of the Corrected Robust Linear Model with Maximum
      Likelihood Classification (CRLMM) genotyping quality on identifying real
      significant genes in a GWAS with large sample sizes. With microarray image data
      from the Wellcome Trust Case-Control Consortium (WTCCC), 1991 individuals with
      coronary artery disease (CAD) and 1500 controls, genetic associations were
      evaluated under various batch sizes and compositions. Experimental designs
      included different batch sizes of 250, 350, 500, 2000 samples with different
      distributions of cases and controls in each batch with either randomized or
      simply combined (4:3 case-control ratios) or separate case-control samples as
      well as whole 3491 samples. The separate composition could create 2-3%
      discordance in the single nucleotide polymorphism (SNP) results for quality
      control/statistical analysis and might contribute to the lack of reproducibility
      between GWAS. CRLMM shows high genotyping accuracy and stability to batch
      effects. According to the genotypic and allelic tests (P<5.0 x 10(-7)), nine
      significant signals on chromosome 9 were found consistently in all batch sizes
      with combined design. Our findings are critical to optimize the reproducibility
      of GWAS and confirm the genetic role in the pathophysiology of CAD.

PMID- 20676073
TI  - An interactive effect of batch size and composition contributes to discordant
      results in GWAS with the CHIAMO genotyping algorithm.
AB  - The discordance in results between independent genome-wide association studies
      (GWAS) indicates the potential for Type I and Type II errors. To identify the
      causes of variability underlying lack of reproducibility, here we present the
      results of a repeatability experiment on GWAS on a cohort of 1991 coronary artery
      disease individuals and 1500 controls (National Blood Service) provided by the
      Wellcome Trust Case Control Consortium. As part of the MicroArray Quality Control
      project, we identified quality control (QC) and association analysis steps with a
      major impact on the identification of candidate markers for possible classifiers.
      Different experimental conditions were used with the CHIAMO calling algorithm to
      assess the effects of batch size and case-control composition on downstream
      association analysis. Results showed that both composition and size create
      discordant single-nucleotide polymorphism (SNP) results for QC and statistical
      analysis and may contribute to the lack of reproducibility in GWAS. An
      interactive effect of batch size and composition contributes to discordant
      results in significantly associated loci. About 800 significant SNPs (Cochran
      Armitage trend test, P<5.0 x 10(-7)) were found for batches of 2000 samples with
      separated cases and controls, whereas only 14 significant markers were found with
      one batch of all samples.

PMID- 20676075
TI  - MutationTaster evaluates disease-causing potential of sequence alterations.

PMID- 20676076
TI  - mrsFAST: a cache-oblivious algorithm for short-read mapping.

PMID- 20676074
TI  - The MicroArray Quality Control (MAQC)-II study of common practices for the
      development and validation of microarray-based predictive models.
AB  - Gene expression data from microarrays are being applied to predict preclinical
      and clinical endpoints, but the reliability of these predictions has not been
      established. In the MAQC-II project, 36 independent teams analyzed six microarray
      data sets to generate predictive models for classifying a sample with respect to
      one of 13 endpoints indicative of lung or liver toxicity in rodents, or of breast
      cancer, multiple myeloma or neuroblastoma in humans. In total, >30,000 models
      were built using many combinations of analytical methods. The teams generated
      predictive models without knowing the biological meaning of some of the endpoints
      and, to mimic clinical reality, tested the models on data that had not been used
      for training. We found that model performance depended largely on the endpoint
      and team proficiency and that different approaches generated models of similar
      performance. The conclusions and recommendations from MAQC-II should be useful
      for regulatory agencies, study committees and independent investigators that
      evaluate methods for global gene expression analysis.

PMID- 20676078
TI  - Hold me tightly LOV.

PMID- 20676079
TI  - Going small is the new big.

PMID- 20676080
TI  - Fishing at the cellular level.

PMID- 20676081
TI  - Going deeper than microscopy: the optical imaging frontier in biology.
AB  - Optical microscopy has been a fundamental tool of biological discovery for more
      than three centuries, but its in vivo tissue imaging ability has been restricted
      by light scattering to superficial investigations, even when confocal or
      multiphoton methods are used. Recent advances in optical and optoacoustic
      (photoacoustic) imaging now allow imaging at depths and resolutions unprecedented
      for optical methods. These abilities are increasingly important to understand the
      dynamic interactions of cellular processes at different systems levels, a major
      challenge of postgenome biology. This Review discusses promising photonic methods
      that have the ability to visualize cellular and subcellular components in tissues
      across different penetration scales. The methods are classified into microscopic,
      mesoscopic and macroscopic approaches, according to the tissue depth at which
      they operate. Key characteristics associated with different imaging
      implementations are described and the potential of these technologies in
      biological applications is discussed.

PMID- 20676082
TI  - Structure of the torque ring of the flagellar motor and the molecular basis for
      rotational switching.
AB  - The flagellar motor drives the rotation of flagellar filaments at hundreds of
      revolutions per second, efficiently propelling bacteria through viscous media.
      The motor uses the potential energy from an electrochemical gradient of cations
      across the cytoplasmic membrane to generate torque. A rapid switch from
      anticlockwise to clockwise rotation determines whether a bacterium runs smoothly
      forward or tumbles to change its trajectory. A protein called FliG forms a ring
      in the rotor of the flagellar motor that is involved in the generation of torque
      through an interaction with the cation-channel-forming stator subunit MotA. FliG
      has been suggested to adopt distinct conformations that induce switching but
      these structural changes and the molecular mechanism of switching are unknown.
      Here we report the molecular structure of the full-length FliG protein, identify
      conformational changes that are involved in rotational switching and uncover the
      structural basis for the formation of the FliG torque ring. This allows us to
      propose a model of the complete ring and switching mechanism in which
      conformational changes in FliG reverse the electrostatic charges involved in
      torque generation.

PMID- 20676083
TI  - A ribosome-associating factor chaperones tail-anchored membrane proteins.
AB  - Hundreds of proteins are inserted post-translationally into the endoplasmic
      reticulum (ER) membrane by a single carboxy-terminal transmembrane domain (TMD).
      During targeting through the cytosol, the hydrophobic TMD of these tail-anchored
      (TA) proteins requires constant chaperoning to prevent aggregation or
      inappropriate interactions. A central component of this targeting system is
      TRC40, a conserved cytosolic factor that recognizes the TMD of TA proteins and
      delivers them to the ER for insertion. The mechanism that permits TRC40 to find
      and capture its TA protein cargos effectively in a highly crowded cytosol is
      unknown. Here we identify a conserved three-protein complex composed of Bat3,
      TRC35 and Ubl4A that facilitates TA protein capture by TRC40. This Bat3 complex
      is recruited to ribosomes synthesizing membrane proteins, interacts with the TMDs
      of newly released TA proteins, and transfers them to TRC40 for targeting.
      Depletion of the Bat3 complex allows non-TRC40 factors to compete for TA
      proteins, explaining their mislocalization in the analogous yeast deletion
      strains. Thus, the Bat3 complex acts as a TMD-selective chaperone that
      effectively channels TA proteins to the TRC40 insertion pathway.

PMID- 20676084
TI  - A copper-containing oxidase catalyzes C-nitrosation in nitrosobenzamide
      biosynthesis.
AB  - Although C-nitroso aromatic compounds have several bioactivities of medicinal
      interest, the biosynthetic enzymes involved in C-nitrosation have remained
      unknown until now. Here, we report the entire biosynthesis pathway of 4-hydroxy-3
      nitrosobenzamide in Streptomyces murayamaensis, in which a tyrosinase-like copper
      containing monooxygenase is responsible for the C-nitrosation. This finding
      indicates diverse catalytic functions of tyrosinase-like copper-containing
      monooxygenases in nature.

PMID- 20676085
TI  - Replication-dependent instability at (CTG) x (CAG) repeat hairpins in human
      cells.
AB  - Instability of (CTG) x (CAG) microsatellite trinucleotide repeat (TNR) sequences
      is responsible for more than a dozen neurological or neuromuscular diseases. TNR
      instability during DNA synthesis is thought to involve slipped-strand or hairpin
      structures in template or nascent DNA strands, although direct evidence for
      hairpin formation in human cells is lacking. We have used targeted recombination
      to create a series of isogenic HeLa cell lines in which (CTG) x (CAG) repeats are
      replicated from an ectopic copy of the Myc (also known as c-myc) replication
      origin. In this system, the tendency of chromosomal (CTG) x (CAG) tracts to
      expand or contract was affected by origin location and the leading or lagging
      strand replication orientation of the repeats, and instability was enhanced by
      prolonged cell culture, increased TNR length and replication inhibition. Hairpin
      cleavage by synthetic zinc finger nucleases in these cells has provided the first
      direct evidence for the formation of hairpin structures during replication in
      vivo.

PMID- 20676086
TI  - Photon-enhanced thermionic emission for solar concentrator systems.
AB  - Solar-energy conversion usually takes one of two forms: the 'quantum' approach,
      which uses the large per-photon energy of solar radiation to excite electrons, as
      in photovoltaic cells, or the 'thermal' approach, which uses concentrated
      sunlight as a thermal-energy source to indirectly produce electricity using a
      heat engine. Here we present a new concept for solar electricity generation,
      photon-enhanced thermionic emission, which combines quantum and thermal
      mechanisms into a single physical process. The device is based on thermionic
      emission of photoexcited electrons from a semiconductor cathode at high
      temperature. Temperature-dependent photoemission-yield measurements from GaN show
      strong evidence for photon-enhanced thermionic emission, and calculated
      efficiencies for idealized devices can exceed the theoretical limits of single
      junction photovoltaic cells. The proposed solar converter would operate at
      temperatures exceeding 200 degrees C, enabling its waste heat to be used to power
      a secondary thermal engine, boosting theoretical combined conversion efficiencies
      above 50%.

PMID- 20676087
TI  - Quantitative prediction of solute strengthening in aluminium alloys.
AB  - Despite significant advances in computational materials science, a quantitative,
      parameter-free prediction of the mechanical properties of alloys has been
      difficult to achieve from first principles. Here, we present a new analytic
      theory that, with input from first-principles calculations, is able to predict
      the strengthening of aluminium by substitutional solute atoms. Solute-dislocation
      interaction energies in and around the dislocation core are first calculated
      using density functional theory and a flexible-boundary-condition method. An
      analytic model for the strength, or stress to move a dislocation, owing to the
      random field of solutes, is then presented. The theory, which has no adjustable
      parameters and is extendable to other metallic alloys, predicts both the energy
      barriers to dislocation motion and the zero-temperature flow stress, allowing for
      predictions of finite-temperature flow stresses. Quantitative comparisons with
      experimental flow stresses at temperature T=78 K are made for Al-X alloys (X=Mg,
      Si, Cu, Cr) and good agreement is obtained.

PMID- 20676088
TI  - Beam pen lithography.
AB  - Lithography techniques are currently being developed to fabricate nanoscale
      components for integrated circuits, medical diagnostics and optoelectronics. In
      conventional far-field optical lithography, lateral feature resolution is
      diffraction-limited. Approaches that overcome the diffraction limit have been
      developed, but these are difficult to implement or they preclude arbitrary
      pattern formation. Techniques based on near-field scanning optical microscopy can
      overcome the diffraction limit, but they suffer from inherently low throughput
      and restricted scan areas. Highly parallel two-dimensional, silicon-based, near
      field scanning optical microscopy aperture arrays have been fabricated, but
      aligning a non-deformable aperture array to a large-area substrate with near
      field proximity remains challenging. However, recent advances in lithographies
      based on scanning probe microscopy have made use of transparent two-dimensional
      arrays of pyramid-shaped elastomeric tips (or 'pens') for large-area, high
      throughput patterning of ink molecules. Here, we report a massively parallel
      scanning probe microscopy-based approach that can generate arbitrary patterns by
      passing 400-nm light through nanoscopic apertures at each tip in the array. The
      technique, termed beam pen lithography, can toggle between near- and far-field
      distances, allowing both sub-diffraction limit (100 nm) and larger features to be
      generated.

PMID- 20676089
TI  - Multifunctional materials: Dry but flexible magnetic materials.

PMID- 20676090
TI  - Making flexible magnetic aerogels and stiff magnetic nanopaper using cellulose
      nanofibrils as templates.
AB  - Nanostructured biological materials inspire the creation of materials with
      tunable mechanical properties. Strong cellulose nanofibrils derived from bacteria
      or wood can form ductile or tough networks that are suitable as functional
      materials. Here, we show that freeze-dried bacterial cellulose nanofibril
      aerogels can be used as templates for making lightweight porous magnetic
      aerogels, which can be compacted into a stiff magnetic nanopaper. The 20-70-nm
      thick cellulose nanofibrils act as templates for the non-agglomerated growth of
      ferromagnetic cobalt ferrite nanoparticles (diameter, 40-120 nm). Unlike solvent
      swollen gels and ferrogels, our magnetic aerogel is dry, lightweight, porous
      (98%), flexible, and can be actuated by a small household magnet. Moreover, it
      can absorb water and release it upon compression. Owing to their flexibility,
      high porosity and surface area, these aerogels are expected to be useful in
      microfluidics devices and as electronic actuators.

PMID- 20676091
TI  - Bioorthogonal chemistry amplifies nanoparticle binding and enhances the
      sensitivity of cell detection.
AB  - Nanoparticles have emerged as key materials for biomedical applications because
      of their unique and tunable physical properties, multivalent targeting
      capability, and high cargo capacity. Motivated by these properties and by current
      clinical needs, numerous diagnostic and therapeutic nanomaterials have recently
      emerged. Here we describe a novel nanoparticle targeting platform that uses a
      rapid, catalyst-free cycloaddition as the coupling mechanism. Antibodies against
      biomarkers of interest were modified with trans-cyclooctene and used as scaffolds
      to couple tetrazine-modified nanoparticles onto live cells. We show that the
      technique is fast, chemoselective, adaptable to metal nanomaterials, and scalable
      for biomedical use. This method also supports amplification of biomarker signals,
      making it superior to alternative targeting techniques including avidin/biotin.

PMID- 20676092
TI  - Activation of the aryl hydrocarbon receptor induces human type 1 regulatory T
      cell-like and Foxp3(+) regulatory T cells.
AB  - The aryl hydrocarbon receptor (AhR) participates in the differentiation of mouse
      regulatory T cells (T(reg) cells) and interleukin 17 (IL-17)-producing helper T
      cells (T(H)17 cells), but its role in human T cell differentiation is unknown. We
      investigated the role of AhR in the differentiation of human induced T(reg) cells
      (iT(reg) cells). We found that AhR activation promoted the differentiation of
      CD4(+)Foxp3(-) T cells, which produce IL-10 and control responder T cells through
      granzyme B. However, activation of AhR in the presence of transforming growth
      factor-beta1 induced Foxp3(+) iT(reg) cells, which suppress responder T cells
      through the ectonucleoside triphosphate diphosphohydrolase CD39. The induction of
      functional Foxp3(+) iT(reg) cells required coordinated action of the
      transcriptional regulators Smad1 and Aiolos. Thus, AhR is a potential target
      through which functional iT(reg) cells could be induced in human autoimmune
      disorders.

PMID- 20676093
TI  - The transmembrane activator TACI triggers immunoglobulin class switching by
      activating B cells through the adaptor MyD88.
AB  - BAFF and APRIL are innate immune mediators that trigger immunoglobulin G (IgG)
      and IgA class-switch recombination (CSR) in B cells by engaging the receptor
      TACI. The mechanism that underlies CSR signaling by TACI remains unknown. Here we
      found that the cytoplasmic domain of TACI encompasses a conserved motif that
      bound MyD88, an adaptor that activates transcription factor NF-kappaB signaling
      pathways via a Toll-interleukin 1 (IL-1) receptor (TIR) domain. TACI lacks a TIR
      domain, yet triggered CSR via the DNA-editing enzyme AID by activating NF-kappaB
      through a Toll-like receptor (TLR)-like MyD88-IRAK1-IRAK4-TRAF6-TAK1 pathway.
      TACI-induced CSR was impaired in mice and humans lacking MyD88 or the kinase
      IRAK4, which indicates that MyD88 controls a B cell-intrinsic, TIR-independent,
      TACI-dependent pathway for immunoglobulin diversification.

PMID- 20676094
TI  - IgT, a primitive immunoglobulin class specialized in mucosal immunity.
AB  - Teleost fish are the most primitive bony vertebrates that contain
      immunoglobulins. In contrast to mammals and birds, these species are devoid of
      immunoglobulin A (IgA) or a functional equivalent. This observation suggests that
      specialization of immunoglobulin isotypes into mucosal and systemic responses
      took place during tetrapod evolution. Challenging that paradigm, here we show
      that IgT, an immunoglobulin isotype of unknown function, acts like a mucosal
      antibody. We detected responses of rainbow trout IgT to an intestinal parasite
      only in the gut, whereas IgM responses were confined to the serum. IgT coated
      most intestinal bacteria. As IgT and IgA are phylogenetically distant
      immunoglobulins, their specialization into mucosal responses probably occurred
      independently by a process of convergent evolution.

PMID- 20676095
TI  - The aryl hydrocarbon receptor interacts with c-Maf to promote the differentiation
      of type 1 regulatory T cells induced by IL-27.
AB  - Type 1 regulatory T cells (Tr1 cells ) that produce interleukin 10 (IL-10) are
      instrumental in the prevention of tissue inflammation, autoimmunity and graft
      versus-host disease. The transcription factor c-Maf is essential for the
      induction of IL-10 by Tr1 cells, but the molecular mechanisms that lead to the
      development of these cells remain unclear. Here we show that the ligand-activated
      transcription factor aryl hydrocarbon receptor (AhR), which was induced by IL-27,
      acted in synergy with c-Maf to promote the development of Tr1 cells. After T cell
      activation under Tr1-skewing conditions, the AhR bound to c-Maf and promoted
      transactivation of the Il10 and Il21 promoters, which resulted in the generation
      of Tr1 cells and the amelioration of experimental autoimmune encephalomyelitis.
      Manipulating AhR signaling could therefore be beneficial in the resolution of
      excessive inflammatory responses.

PMID- 20676096
TI  - Genome-wide association study identifies 1p36.22 as a new susceptibility locus
      for hepatocellular carcinoma in chronic hepatitis B virus carriers.
AB  - To identify susceptibility variants for hepatitis B virus (HBV)-related
      hepatocellular carcinoma (HCC), we conducted a genome-wide association study by
      genotyping 440,794 SNPs in 355 chronic HBV carriers with HCC and 360 chronic HBV
      carriers without HCC, all of Chinese ancestry. We identified one intronic SNP
      (rs17401966) in KIF1B on chromosome 1p36.22 that was highly associated with HBV
      related HCC and confirmed this association in five additional independent
      samples, consisting of 1,962 individuals with HCC, 1,430 control subjects and 159
      family trios. Across the six studies, the association with rs17401966 was highly
      statistically significant (joint odds ratio = 0.61, P = 1.7 x 10(-18)). In
      addition to KIF1B, the association region tagged two other plausible causative
      genes, UBE4B and PGD. Our findings provide evidence that the 1p36.22 locus
      confers susceptibility to HBV-related HCC, and suggest that KIF1B-, UBE4B- or PGD
      related pathways might be involved in the pathogenesis of this malignancy.

PMID- 20676097
TI  - KLF1 regulates BCL11A expression and gamma- to beta-globin gene switching.
AB  - We show that knockdown of KLF1 in human and mouse adult erythroid progenitors
      markedly reduces BCL11A levels and increases human gamma-globin/beta-globin
      expression ratios. These results suggest that KLF1 controls globin gene switching
      by directly activating beta-globin and indirectly repressing gamma-globin gene
      expression. Controlled knockdown of KLF1 in adult erythroid progenitors may
      provide a method to activate fetal hemoglobin expression in individuals with beta
      thalassemia or sickle cell disease.

PMID- 20676098
TI  - Genome-wide association study identifies five new susceptibility loci for
      prostate cancer in the Japanese population.
AB  - Prostate cancer is one of the most common malignancies in males throughout the
      world, and its incidence is increasing in Asian countries. We carried out a
      genome-wide association study and replication study using 4,584 Japanese men with
      prostate cancer and 8,801 control subjects. From the thirty-one associated SNPs
      reported in previous genome-wide association studies in European populations, we
      confirmed the association of nine SNPs at P < 1.0 x 10(-7) and ten SNPs at P <
      0.05 in the Japanese population. The remaining 12 SNPs showed no association (P >
      0.05). In addition, we report here five new loci for prostate cancer
      susceptibility, at 5p15 (lambda-corrected probability P(GC) = 3.9 x 10(-18)),
      GPRC6A/RFX6 (P(GC) = 1.6 x 10(-12)), 13q22 (P(GC) = 2.8 x 10(-9)), C2orf43 (P(GC)
      = 7.5 x 10(-8)) and FOXP4 (P(GC) = 7.6 x 10(-8)). These findings advance our
      understanding of the genetic basis of prostate carcinogenesis and also highlight
      the genetic heterogeneity of prostate cancer susceptibility among different
      ethnic populations.

PMID- 20676099
TI  - Haploinsufficiency for the erythroid transcription factor KLF1 causes hereditary
      persistence of fetal hemoglobin.
AB  - Hereditary persistence of fetal hemoglobin (HPFH) is characterized by persistent
      high levels of fetal hemoglobin (HbF) in adults. Several contributory factors,
      both genetic and environmental, have been identified but others remain elusive.
      HPFH was found in 10 of 27 members from a Maltese family. We used a genome-wide
      SNP scan followed by linkage analysis to identify a candidate region on
      chromosome 19p13.12-13. Sequencing revealed a nonsense mutation in the KLF1 gene,
      p.K288X, which ablated the DNA-binding domain of this key erythroid
      transcriptional regulator. Only family members with HPFH were heterozygous
      carriers of this mutation. Expression profiling on primary erythroid progenitors
      showed that KLF1 target genes were downregulated in samples from individuals with
      HPFH. Functional assays suggested that, in addition to its established role in
      regulating adult globin expression, KLF1 is a key activator of the BCL11A gene,
      which encodes a suppressor of HbF expression. These observations provide a
      rationale for the effects of KLF1 haploinsufficiency on HbF levels.

PMID- 20676100
TI  - Hybrid molecular structure of the giant protease tripeptidyl peptidase II.
AB  - Tripeptidyl peptidase II (TPP II) is the largest known eukaryotic protease (6
      MDa). It is believed to act downstream of the 26S proteasome, cleaving
      tripeptides from the N termini of longer peptides, and it is implicated in
      numerous cellular processes. Here we report the structure of Drosophila TPP II
      determined by a hybrid approach. We solved the structure of the dimer by X-ray
      crystallography and docked it into the three-dimensional map of the holocomplex,
      which we obtained by single-particle cryo-electron microscopy. The resulting
      structure reveals the compartmentalization of the active sites inside a system of
      chambers and suggests the existence of a molecular ruler determining the size of
      the cleavage products. Furthermore, the structure suggests a model for activation
      of TPP II involving the relocation of a flexible loop and a repositioning of the
      active-site serine, coupling it to holocomplex assembly and active-site
      sequestration.

PMID- 20676101
TI  - Novel insights into K+ selectivity from high-resolution structures of an open K+
      channel pore.
AB  - K+ channels are highly selective for K+ over Na+. Here we present several crystal
      structures of the MthK K+ channel pore at up to 1.45-A resolution. The MthK
      selectivity filter maintains a conductive conformation even in the absence of K+,
      allowing the channel to conduct Na+. The high-resolution structures, along with
      single-channel recordings, allow for an accurate analysis of how K+ competes with
      Na+ in a conductive selectivity filter. At high K+ concentrations, two K+ ions
      equivalently occupy the four sites in the selectivity filter, whereas at low
      K+/high Na+ concentrations, a single K+ ion remains bound in the selectivity
      filter, preferably at site 1 or site 3. This single K+ binding at low
      concentration effectively blocks the permeation of Na+, providing a structural
      basis for the anomalous mole-fraction effect, a key property of multi-ion pores.

PMID- 20676102
TI  - Heterochromatin formation in the mouse embryo requires critical residues of the
      histone variant H3.3.
AB  - In mammals, oocyte fertilization by sperm initiates development. This is followed
      by epigenetic reprogramming of both parental genomes, which involves the de novo
      establishment of chromatin domains. In the mouse embryo, methylation of histone
      H3 establishes an epigenetic asymmetry and is predominant in the maternal
      pronucleus. However, the roles of differential incorporation of histone H3
      variants in the parental chromatin, and of modified residues within specific
      histone variants, have not been addressed. Here we show that the histone variant
      H3.3, and in particular lysine 27, is required for the establishment of
      heterochromatin in the mouse embryo. H3.3 localizes to paternal pericentromeric
      chromatin during S phase at the time of transcription of pericentromeric repeats.
      Mutation of H3.3 K27, but not of H3.1 K27, results in aberrant accumulation of
      pericentromeric transcripts, HP1 mislocalization, dysfunctional chromosome
      segregation and developmental arrest. This phenotype is rescued by injection of
      double-stranded RNA (dsRNA) derived from pericentromeric transcripts, indicating
      a functional link between H3.3K27 and the silencing of such regions by means of
      an RNA-interference (RNAi) pathway. Our work demonstrates a role for a modifiable
      residue within a histone-variant-specific context during reprogramming and
      identifies a novel function for mammalian H3.3 in the initial formation of dsRNA
      dependent heterochromatin.

PMID- 20676103
TI  - Deletion of the potassium channel Kv12.2 causes hippocampal hyperexcitability and
      epilepsy.
AB  - We found the voltage-gated K+ channel Kv12.2 to be a potent regulator of
      excitability in hippocampal pyramidal neurons. Genetic deletion and pharmacologic
      block of Kv12.2 substantially reduced the firing threshold of these neurons.
      Kv12.2-/- (also known as Kcnh3-/-) mice showed signs of persistent neuronal
      hyperexcitability including frequent interictal spiking, spontaneous seizures and
      increased sensitivity to the chemoconvulsant pentylenetetrazol.

PMID- 20676104
TI  - Regulation of fast-spiking basket cell synapses by the chloride channel ClC-2.
AB  - Parvalbumin-expressing, fast-spiking basket cells are important for the
      generation of synchronous, rhythmic population activities in the hippocampus. We
      found that GABAA receptor-mediated synaptic inputs from murine parvalbumin
      expressing basket cells were selectively modulated by the membrane voltage- and
      intracellular chloride-dependent chloride channel ClC-2. Our data reveal a
      previously unknown cell type-specific regulation of intracellular chloride
      homeostasis in the perisomatic region of hippocampal pyramidal neurons.

PMID- 20676105
TI  - Calcium action potentials in hair cells pattern auditory neuron activity before
      hearing onset.
AB  - We found rat central auditory neurons to fire action potentials in a precise
      sequence of mini-bursts before the age of hearing onset. This stereotyped pattern
      was initiated by hair cells in the cochlea, which trigger brief bursts of action
      potentials in auditory neurons each time they fire a Ca2+ spike. By generating
      theta-like activity, hair cells may limit the influence of synaptic depression in
      developing auditory circuits and promote consolidation of synapses.

PMID- 20676106
TI  - MicroRNA-132-mediated loss of p120RasGAP activates the endothelium to facilitate
      pathological angiogenesis.
AB  - Although it is well established that tumors initiate an angiogenic switch, the
      molecular basis of this process remains incompletely understood. Here we show
      that the miRNA miR-132 acts as an angiogenic switch by targeting p120RasGAP in
      the endothelium and thereby inducing neovascularization. We identified miR-132 as
      a highly upregulated miRNA in a human embryonic stem cell model of vasculogenesis
      and found that miR-132 was highly expressed in the endothelium of human tumors
      and hemangiomas but was undetectable in normal endothelium. Ectopic expression of
      miR-132 in endothelial cells in vitro increased their proliferation and tube
      forming capacity, whereas intraocular injection of an antagomir targeting miR
      132, anti-miR-132, reduced postnatal retinal vascular development in mice. Among
      the top-ranking predicted targets of miR-132 was p120RasGAP, which we found to be
      expressed in normal but not tumor endothelium. Endothelial expression of miR-132
      suppressed p120RasGAP expression and increased Ras activity, whereas a miRNA
      resistant version of p120RasGAP reversed the vascular response induced by miR
      132. Notably, administration of anti-miR-132 inhibited angiogenesis in wild-type
      mice but not in mice with an inducible deletion of Rasa1 (encoding p120RasGAP).
      Finally, vessel-targeted nanoparticle delivery of anti-miR-132 restored
      p120RasGAP expression in the tumor endothelium, suppressed angiogenesis and
      decreased tumor burden in an orthotopic xenograft mouse model of human breast
      carcinoma. We conclude that miR-132 acts as an angiogenic switch by suppressing
      endothelial p120RasGAP expression, leading to Ras activation and the induction of
      neovascularization, whereas the application of anti-miR-132 inhibits
      neovascularization by maintaining vessels in the resting state.

PMID- 20676107
TI  - Reciprocal coupling of coagulation and innate immunity via neutrophil serine
      proteases.
AB  - Blood neutrophils provide the first line of defense against pathogens but have
      also been implicated in thrombotic processes. This dual function of neutrophils
      could reflect an evolutionarily conserved association between blood coagulation
      and antimicrobial defense, although the molecular determinants and in vivo
      significance of this association remain unclear. Here we show that major
      microbicidal effectors of neutrophils, the serine proteases neutrophil elastase
      and cathepsin G, together with externalized nucleosomes, promote coagulation and
      intravascular thrombus growth in vivo. The serine proteases and extracellular
      nucleosomes enhance tissue factor- and factor XII-dependent coagulation in a
      process involving local proteolysis of the coagulation suppressor tissue factor
      pathway inhibitor. During systemic infection, activation of coagulation fosters
      compartmentalization of bacteria in liver microvessels and reduces bacterial
      invasion into tissue. In the absence of a pathogen challenge, neutrophil-derived
      serine proteases and nucleosomes can contribute to large-vessel thrombosis, the
      main trigger of myocardial infarction and stroke. The ability of coagulation to
      suppress pathogen dissemination indicates that microvessel thrombosis represents
      a physiological tool of host defense.

PMID- 20676109
TI  - Automated imaging with ScanLag reveals previously undetectable bacterial growth
      phenotypes.
AB  - We developed an automated system, ScanLag, that measures in parallel the delay in
      growth (lag time) and growth rate of thousands of cells. Using ScanLag, we
      detected small subpopulations of bacteria with dramatically increased lag time
      upon starvation. By screening a library of Escherichia coli deletion mutants, we
      achieved two-dimensional mapping of growth characteristics, which showed that
      ScanLag enables multidimensional screens for quantitative characterization and
      identification of rare phenotypic variants.

PMID- 20676108
TI  - Mechanical regulation of cell function with geometrically modulated elastomeric
      substrates.
AB  - We report the establishment of a library of micromolded elastomeric micropost
      arrays to modulate substrate rigidity independently of effects on adhesive and
      other material surface properties. We demonstrated that micropost rigidity
      impacts cell morphology, focal adhesions, cytoskeletal contractility and stem
      cell differentiation. Furthermore, early changes in cytoskeletal contractility
      predicted later stem cell fate decisions in single cells.

PMID- 20676110
TI  - 2010 gene therapy year in review.

PMID- 20676114
TI  - Growth inhibition mediated by PSP94 or CRISP-3 is prostate cancer cell line
      specific.
AB  - The prostate secretory protein of 94 amino acids (PSP94) has been shown to
      interact with cysteine-rich secretory protein 3 (CRISP-3) in human seminal
      plasma. Interestingly, PSP94 expression is reduced or lost in the majority of the
      prostate tumours, whereas CRISP-3 expression is upregulated in prostate cancer
      compared with normal prostate tissue. To obtain a better understanding of the
      individual roles these proteins have in prostate tumourigenesis and the
      functional relevance of their interaction, we ectopically expressed either PSP94
      or CRISP-3 alone or PSP94 along with CRISP-3 in three prostate cell lines (PC3,
      WPE1-NB26 and LNCaP) and performed growth inhibition assays. Reverse
      transcription-polymerase chain reaction and Western blot analysis were used to
      screen prostate cell lines for PSP94 and CRISP-3 expression. Mammalian expression
      constructs for human PSP94 and CRISP-3 were also generated and the expression,
      localization and secretion of recombinant protein were assayed by transfection
      followed by Western blot analysis and immunofluorescence assay. The effect that
      ectopic expression of PSP94 or CRISP-3 had on cell growth was studied by
      clonogenic survival assay following transfection. To evaluate the effects of co
      expression of the two proteins, stable clones of PC3 that expressed PSP94 were
      generated. They were subsequently transfected with a CRISP-3 expression construct
      and subjected to clonogenic survival assay. Our results showed that PSP94 and
      CRISP-3 could each induce growth inhibition in a cell line specific manner.
      Although the growth of CRISP-3-positive cell lines was inhibited by PSP94, growth
      inhibition mediated by CRISP-3 was not affected by the presence or absence of
      PSP94. This suggests that CRISP-3 may participate in PSP94-independent activities
      during prostate tumourigenesis.

PMID- 20676115
TI  - Prevalence of premature ejaculation in young and middle-aged men in Korea: a
      multicenter internet-based survey from the Korean Andrological Society.
AB  - In this study, we aimed to investigate the prevalence and perception of premature
      ejaculation (PE) in young and middle-aged Korean men. The study was conducted
      using an Internet-assisted questionnaire. A total of 2 037 Korean male adults,
      aged 20 years or older, were randomly sampled based on age and residency. The
      questionnaire developed by the PE Study Group of the Korean Andrological Society
      includes four categories (overall sexual function, symptoms, distress and
      treatment) with a total of 16 questions. For each question, symptoms were
      evaluated by a scale ranging from 0 to 10. Intravaginal ejaculation latency time
      was '5-10 min' in 38.6%, followed by 'longer than 10 min' in 29.9%, '2-5 min' in
      23.6%, '1-2 min' in 5.4% and 'shorter than 1 min' in 2.5%. In our series, 27.5%
      of respondents reported having PE. Control over ejaculation within a recent 3
      month period was 6.2 points on average. Respondent complaints of PE-related
      stress averaged 7.1 points and stress-related complaints from sexual partners
      averaged 7.1 points. The effect of PE on sexual life was 6.8 points. Of the
      respondents determined as having PE, 42.6% responded that they were inclined to
      receive treatment. Results from this study suggest that the prevalence of PE
      diagnosed by the respondent on his own was approximately 27.5% in young and
      middle-aged men in Korea. PE-related stress had a significant effect on the
      stress, sexual activity and quality of life of the respondent and his sexual
      partner.

PMID- 20676116
TI  - Significance of age and comorbidity as prognostic indicators for patients with
      bladder cancer.
AB  - The aim of this study was to determine the impact that age and comorbidity status
      have on both overall and bladder cancer-specific survival of bladder cancer
      patients. We obtained medical information pertaining to a population of 528
      patients with newly diagnosed bladder cancer from Chung-Ang University Hospital
      cancer registry. The Adult Comorbidity Evaluation-27 (ACE-27) test, which has
      been previously validated in adult cancer patients, was used to assess
      comorbidity. We evaluated differences in the demographic and clinical
      characteristics of included patients, as well as differences in the treatments
      they received after categorizing them by age. The median age at the time of
      bladder cancer diagnosis of the entire cohort was 63 years, and the median follow
      up time was 97 months. Of the 528 patients who were included in our study, 303
      had at least one comorbid condition and 249 died during the follow-up period.
      When patients were stratified by age, we found that older patients had a higher
      proportion of severe comorbidities (P < 0.01) than younger patients, and that a
      lower proportion of them underwent radical cystectomy for invasive bladder cancer
      (IBC) (P < 0.01). By multivariate analysis, we found that older age was
      predictive of lower overall survival (OS) and bladder cancer-specific survival
      (BCSS) rates among patients with superficial bladder cancer (SBC) and of lower OS
      rates among patients with IBC. We also found that moderate-severe comorbidity
      status and treatment through a bladder-conserving approach were predictive of
      lower OS and cancer-specific survival rates among patients with IBC. The
      disparity between overall deaths and bladder cancer deaths was shown in SBC and
      increased along with age and higher comorbidity. Age and comorbidity were found
      to be independent predictive factors of OS and BCSS among bladder cancer
      patients, and explained the disparity that we observed between overall bladder
      cancer-specific mortality rates.

PMID- 20676117
TI  - Poly(ADP-ribose) polymerase inhibitors as promising cancer therapeutics.
AB  - The year of 2005 was a watershed in the history of poly(ADP-ribose) polymerase
      (PARP) inhibitors due to the important findings of selective killing in BRCA
      deficient cancers by PARP inhibition. The findings made PARP inhibition one of
      the most promising new therapeutic approaches to cancers, especially to those
      with specific defects. With AZD2281 and BSI-201 entering phase III clinical
      trials, the final application of PARP inhibitors in clinic would come true soon.
      This current paper will review the major advances in targeting PARP for cancer
      therapy and discuss the existing questions, the answers to which may influence
      the future of PARP inhibitors as cancer therapeutics.

PMID- 20676118
TI  - Non-peptidic glucose-like peptide-1 receptor agonists: aftermath of a
      serendipitous discovery.
AB  - Glucagon-like peptide-1 (GLP-1) receptor is an ideal target in the development of
      incretin-based therapies for diabetes and obesity. Two approaches have been
      adopted: GLP-1 receptor agonists that mimic the effects of native GLP-1 and
      dipeptidyl peptidase-4 inhibitors that increase endogenous GLP-1 levels. During
      the past two decades, search for orally active, non-peptidic GLP-1 receptor
      agonists has been the focal point of research and development activities in many
      multinational pharmaceutical companies. Such efforts have not resulted in any
      success thus far. Serendipitous discovery of substituted cyclobutanes represented
      by Boc5 as a new class of GLP-1 receptor agonists led us to believe that a small
      molecule approach to class B G-protein coupled receptor agonism is no longer a
      fantasy but a reality. However, major obstacles still pose great challenges, and
      the reasons of which are discussed in this perspectives.

PMID- 20676119
TI  - Hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels in the
      regulation of midbrain dopamine systems.
AB  - Hyperpolarization-activated, cyclic nucleotide-gated channels (HCN channels) are
      expressed widely in the brain and invovled in various neuronal activities,
      including the control of neuronal rhythmic activity, setting the resting membrane
      potential, as well as dendritic integration. HCN channels also participate in the
      regulation of spontaneous activity of midbrain dopamine (DA) neurons to some
      extent. In slice preparations of midbrain, a hyperpolarization-activated non
      selective cation current (Ih) mediated by the channels has been proposed as an
      electrophysiological marker to identify DA neurons. Recent evidence, however,
      shows that the functional roles of HCN channels in midbrain DA neurons are
      obviously underestimated. Here, we review the recent advances in the studies of
      the functional roles of Ih in midbrain DA neurons and further, their involvement
      in drug addiction and Parkinson's disease.

PMID- 20676120
TI  - Chromosome 1q21 amplification and oncogenes in hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is among the most lethal of human malignancies.
      During human multistep hepatocarcinogenesis, genomic gain represents an important
      mechanism in the activation of proto-oncogenes. In many circumstances, activated
      oncogenes hold clinical implications both as prognostic markers and targets for
      cancer therapeutics. Gain of chromosome 1q copy is one of the most frequently
      detected alterations in HCC and 1q21 is the most frequent minimal amplifying
      region (MAR). A better understanding of the physiological and pathophysiological
      roles of target genes within 1q21 amplicon will significantly improve our
      knowledge in HCC pathogenesis, and may lead to a much more effective management
      of HCC bearing amplification of 1q21. Such knowledge has long term implications
      for the development of new therapeutic strategies for HCC treatment. Our research
      group and others, focused on the identification and characterization of 1q21
      target genes such as JTB, CKS1B, and CHD1L in HCC progression. In this review, we
      will summarize the current scientific knowledge of known target genes within 1q21
      amplicon and the precise oncogenic mechanisms of CHD1L will be discussed in
      detail.

PMID- 20676122
TI  - Pain management: Fibromyalgia drugs are 'as good as it gets' in chronic pain.

PMID- 20676121
TI  - Cathelicidins in inflammation and tissue repair: Potential therapeutic
      applications for gastrointestinal disorders.
AB  - Cathelicidins, a family of host defense peptides, are highly expressed during
      infection, inflammation and wound healing. These peptides not only have broad
      spectrum antimicrobial activities, but also modulate inflammation by altering
      cytokine response and chemoattraction of inflammatory cells in diseased tissues.
      In this connection, a mouse cathelicidin has been demonstrated to prevent
      inflammation in the colon through enhancing mucus production and reducing
      production of pro-inflammatory cytokines. In addition, cathelicidins promote
      wound healing through stimulation of re-epithelialization and angiogenesis at
      injured tissues. In an animal model of gastric ulceration, the rat cathelicidin
      promotes ulcer healing by inducing proliferation of gastric epithelial cells both
      in vitro and in vivo. In conclusion, cathelicidins represent an important group
      of effector molecules in the innate immune system that operates a complex
      integration of inflammation and tissue repair in the gastrointestinal mucosa and
      other organs.

PMID- 20676123
TI  - Vasculitis syndromes: Not losing sight is the issue in GCA management.

PMID- 20676124
TI  - Therapy: Challenging the course of RA: time for drug-free remission?

PMID- 20676125
TI  - A previously unrecognized promoter of LMO2 forms part of a transcriptional
      regulatory circuit mediating LMO2 expression in a subset of T-acute lymphoblastic
      leukaemia patients.
AB  - The T-cell oncogene Lim-only 2 (LMO2) critically influences both normal and
      malignant haematopoiesis. LMO2 is not normally expressed in T cells, yet ectopic
      expression is seen in the majority of T-acute lymphoblastic leukaemia (T-ALL)
      patients with specific translocations involving LMO2 in only a subset of these
      patients. Ectopic lmo2 expression in thymocytes of transgenic mice causes T-ALL,
      and retroviral vector integration into the LMO2 locus was implicated in the
      development of clonal T-cell disease in patients undergoing gene therapy. Using
      array-based chromatin immunoprecipitation, we now demonstrate that in contrast to
      B-acute lymphoblastic leukaemia, human T-ALL samples largely use promoter
      elements with little influence from distal enhancers. Active LMO2 promoter
      elements in T-ALL included a previously unrecognized third promoter, which we
      demonstrate to be active in cell lines, primary T-ALL patients and transgenic
      mice. The ETS factors ERG and FLI1 previously implicated in lmo2-dependent mouse
      models of T-ALL bind to the novel LMO2 promoter in human T-ALL samples, while in
      return LMO2 binds to blood stem/progenitor enhancers in the FLI1 and ERG gene
      loci. Moreover, LMO2, ERG and FLI1 all regulate the +1 enhancer of HHEX/PRH,
      which was recently implicated as a key mediator of early progenitor expansion in
      LMO2-driven T-ALL. Our data therefore suggest that a self-sustaining triad of
      LMO2/ERG/FLI1 stabilizes the expression of important mediators of the leukaemic
      phenotype such as HHEX/PRH.

PMID- 20676126
TI  - Targeting anthracyclines in early breast cancer: new candidate predictive
      biomarkers emerge.
AB  - The search for a predictive marker of sensitivity to anthracycline-based
      chemotherapy has proven challenging. Despite human epidermal growth factor
      receptor 2 (HER2) being a strong prognostic marker in breast cancer, the only
      therapies with which there is a recognized functional link to the HER2 oncogene
      are those directly targeting the molecule itself. Despite this, HER2 has been
      extensively assessed as a predictive marker in a variety of chemotherapy regimens
      including anthracyclines. Analysis of anthracycline response in patients with
      HER2 amplification has given conflicting results. This led to the suggestion that
      HER2 amplification was acting as a surrogate for the gene encoding topoisomerase
      IIalpha (TOP2A), a direct cellular target of anthracyclines. Despite an
      attractive functional link between TOP2A and anthracyclines, published studies
      have failed to show strong evidence of an interaction between TOP2A genetic
      aberrations and anthracycline response. A number of other biomarkers have also
      been assessed for their role in predicting anthracycline response, including TP53
      (tumour protein 53) and BRCA1 (breast cancer 1, early onset), together with an
      increasing emergence of gene expression profiling to produce predictive
      signatures of response. Moreover, recent evidence has emerged from presentations
      suggesting new candidate markers of response that warrant further investigation:
      Chr17CEP duplication and tissue inhibitor of metalloproteases 1. This review will
      discuss research into HER2 and TOP2A as predictive markers of anthracycline
      response and will focus on current research into other possible candidate
      predictive markers.

PMID- 20676127
TI  - Sumoylation of ING2 regulates the transcription mediated by Sin3A.
AB  - ING2 (inhibitor of growth 2) is a candidate tumor-suppressor gene involved in
      cell cycle control, apoptosis and senescence. Although the functions of ING2
      within the chromatin remodeling complex Sin3A/histone deacetylase (HDAC) and in
      the p53 pathway have been described, how ING2 itself is regulated remains
      unknown. In this study we report for the first time that ING2 can be sumoylated
      by small ubiquitin-like modifier 1 (SUMO1) on lysine 195 both in vitro and in
      vivo. Strikingly, ING2 sumoylation enhances its association with Sin3a. We
      provide evidences that ING2 can bind to the promoter of genes to mediate their
      expression and that sumoylation of ING2 is required for this binding to some of
      these genes. Among them, we identified the gene TMEM71 (transmembrane protein
      71), whose expression is regulated by ING2 sumoylation. ING2 must be sumoylated
      to bind to the promoter of TMEM71 and to recruit the Sin3A chromatin-modifying
      complex to this promoter, in order to regulate TMEM71 transcription. Hence,
      sumoylation of ING2 enhances its binding to the Sin3A/HDAC complex and is
      required to regulate gene transcriptions.

PMID- 20676128
TI  - EGFRvIV: a previously uncharacterized oncogenic mutant reveals a kinase
      autoinhibitory mechanism.
AB  - Tumor cells often subvert normal regulatory mechanisms of signal transduction.
      This study shows this principle by studying yet uncharacterized mutants of the
      epidermal growth factor receptor (EGFR) previously identified in glioblastoma
      multiforme, which is the most aggressive brain tumor in adults. Unlike the well
      characterized EGFRvIII mutant form, which lacks a portion of the ligand-binding
      cleft within the extracellular domain, EGFRvIVa and EGFRvIVb lack internal
      segments distal to the intracellular tyrosine kinase domain. By constructing the
      mutants and by ectopic expression in naive cells, we show that both mutants
      confer an oncogenic potential in vitro, as well as tumorigenic growth in animals.
      The underlying mechanisms entail constitutive receptor dimerization and basal
      activation of the kinase domain, likely through a mechanism that relieves a
      restraining molecular fold, along with stabilization due to association with
      HSP90. Phosphoproteomic analyses delineated the signaling pathways preferentially
      engaged by EGFRvIVb-identified unique substrates. This information, along with
      remarkable sensitivities to tyrosine kinase blockers and to a chaperone
      inhibitor, proposes strategies for pharmacological interception in brain tumors
      harboring EGFRvIV mutations.

PMID- 20676129
TI  - Hsa-miR-9 methylation status is associated with cancer development and metastatic
      recurrence in patients with clear cell renal cell carcinoma.
AB  - The long-term prognosis for clear cell renal cell carcinoma (ccRCC) is
      dramatically altered by the development of metastatic recurrence. However, there
      are very few indicators that can predict which patient will develop a recurrence.
      MicroRNAs regulate many cellular processes and have been shown to be associated
      with cancer development and recurrence. More recently it has been shown that
      microRNA genes can be epigenetically modified in cancer, resulting in aberrant
      silencing of microRNA genes with tumor suppressor functions. In this study, we
      show that two genes encoding for hsa-miR-9 are significantly hypermethylated in
      ccRCC tumors compared with adjacent normal tissues (P-value <0.001 for both miR-9
      1 and miR-9-3) resulting in decreased expression, and that the methylation of
      these genes was more significant in DNA obtained from the primary tumor for
      patients who developed a recurrence (P-value: 0.012 and 0.009 for miR-9-1 and miR
      9-3, respectively) than in tumors from nonrecurrent patients. Furthermore,
      methylation of miR-9-3 was significantly associated with an increased risk of
      recurrence (hazard ratio: 5.85, 95% confidence intervals: 1.30-26.35) and high
      methylation levels of either miR-9-1 or miR-9-3 resulted in a significant, nearly
      30-month decrease in recurrence-free survival time (P-value: 0.034 and 0.007 for
      miR-9-1 and miR-9-3, respectively). Our results demonstrate that hsa-miR-9 is
      involved in the development of ccRCC while also having a role in the development
      of metastatic recurrence.

PMID- 20676131
TI  - Connexin43 inhibits the oncogenic activity of c-Src in C6 glioma cells.
AB  - One of the characteristics of gliomas is a decrease in the expression of
      connexin43, a protein that forms gap junctions. Restoring connexin43 expression
      in glioma cells reduces their exacerbated rate of cell growth, although it is not
      yet known how connexin43 modifies the expression of genes involved in cell
      proliferation. Here, we show that restoring connexin43 to C6 glioma cells impedes
      their progression from G0/G1 to the S phase of the cell cycle by reducing
      retinoblastoma phosphorylation and cyclin E expression through the upregulation
      of p21 and p27. Interestingly, connexin43 diminishes the oncogenic activity of c
      Src exhibited by glioma cells. By studying a Tyr247 and Tyr265 mutant connexin43,
      we show that these residues are required for connexin43 to inhibit c-Src activity
      and cell proliferation. In conclusion, by acting as a substrate of c-Src,
      connexin43 reduces its oncogenic activity and decreases the rate of glioma cell
      proliferation, potentially an early step in the antiproliferative effects of
      connexin43. Although c-Src is known to phosphorylate connexin43, this study
      provides the first evidence that connexin43 can also inhibit c-Src activity.

PMID- 20676130
TI  - TGFbeta signaling in head and neck squamous cell carcinoma.
AB  - Transforming growth factor beta (TGFbeta) is a key regulator of epithelial cell
      proliferation, immune function and angiogenesis. Because TGFbeta signaling
      maintains epithelial homeostasis, dysregulated TGFbeta signaling is common in
      many malignancies, including head and neck squamous cell carcinoma (HNSCC).
      Defective TGFbeta signaling in epithelial cells causes hyperproliferation,
      reduced apoptosis and increased genomic instability, and the compensatory
      increase in TGFbeta production by tumor epithelial cells with TGFbeta signaling
      defects further promotes tumor growth and metastases by increasing angiogenesis
      and inflammation in tumor stromal cells. Here, we review the mouse models that we
      used to study TGFbeta signaling in HNSCC.

PMID- 20676132
TI  - c-MYC overexpression with loss of Ink4a/Arf transforms bone marrow stromal cells
      into osteosarcoma accompanied by loss of adipogenesis.
AB  - The development of cancer is due to the growth and proliferation of transformed
      normal cells. Recent evidence suggests that the nature of oncogenic stress and
      the state of the cell of origin critically affect both tumorigenic activity and
      tumor histological type. However, this mechanistic relationship in mesenchymal
      tumors is currently largely unexplored. To clarify these issues, we established a
      mouse osteosarcoma (OS) model through overexpression of c-MYC in bone marrow
      stromal cells (BMSCs) derived from Ink4a/Arf (-/-) mice. Single-cell cloning
      revealed that c-MYC-expressing BMSCs are composed of two distinctly different
      clones: highly tumorigenic cells, similar to bipotent-committed osteochondral
      progenitor cells, and low-tumorigenic tripotent cells, similar to mesenchymal
      stem cells (MSCs). It is noteworthy that both bipotent and tripotent cells were
      capable of generating histologically similar, lethal OS, suggesting that both
      committed progenitor cells and MSCs can become OS cells of origin. Shifting
      mesenchymal differentiation by depleting PPARgamma in tripotent MSC-like cells
      and overexpressing PPARgamma in bipotent cells affected cell proliferation and
      tumorigenic activity. Our findings indicate that differentiation potential has a
      key role in OS tumorigenic activity, and that the suppression of adipogenic
      ability is a critical factor for the development of OS.

PMID- 20676133
TI  - Multiple modification and protein interaction signals drive the Ring finger
      protein 11 (RNF11) E3 ligase to the endosomal compartment.
AB  - Ring finger protein 11 (RNF11) is a small RING E3-ligase overexpressed in
      numerous human prostate, colon and invasive breast cancers. Although functional
      studies have implicated RNF11 in a variety of biological processes, including
      signal transduction and apoptosis, the molecular mechanisms underlying its
      function are still poorly understood. In this study we show that RNF11 is a
      membrane-associated E3 ligase co-localizing with markers of both the early and
      the recycling endosomes. Several modification and protein interaction signals in
      the RNF11 sequence are shown to affect its compartmentalization. Membrane binding
      requires two acylation motifs driving the myristoylation of Gly2 and the S
      palmitoylation of Cys4. Accordingly, genetic removal of the myristoylating signal
      results in diffuse staining, whereas an RNF11 protein mutated in the
      palmitoylation signal is retained in compartments of the early secretory pathway.
      However, amino-terminal fusion to green fluorescent protein of a 10-residue
      peptide containing both acylation signals re-localizes the chimera to the plasma
      membrane, but it is not sufficient to direct it to the recycling compartment
      suggesting that additional signals contribute to the correct localization. In
      addition, we show that membrane anchoring through acylation is necessary for
      RNF11 to be post-translationally modified by the addition of several ubiquitin
      moieties and that loss of acylation severely impairs the in vivo ubiquitination
      mediated by the HECT E3-ligases Itch and Nedd4. Finally, in cells transfected
      with RNF11 we observe a correlation between high RNF11 expression, as in tumor
      cells, and a swelling of the endosomal compartment suggesting a possible role of
      the dysregulation of the endosome compartment in tumorigenesis.

PMID- 20676134
TI  - Helicobacter pylori CagA targets gastric tumor suppressor RUNX3 for proteasome
      mediated degradation.
AB  - Chronic infection with cagA-positive Helicobacter pylori is the strongest risk
      factor for the development of gastric adenocarcinoma. The cagA gene product CagA
      is injected into gastric epithelial cells and disturbs cellular functions by
      physically interacting with and deregulating a variety of cellular signaling
      molecules. RUNX3 is a tumor suppressor in many tissues, and it is frequently
      inactivated in gastric cancer. In this study, we show that H. pylori infection
      inactivates the gastric tumor suppressor RUNX3 in a CagA-dependent manner. CagA
      directly associates with RUNX3 through a specific recognition of the PY motif of
      RUNX3 by a WW domain of CagA. Deletion of the WW domains of CagA or mutation of
      the PY motif in RUNX3 abolishes the ability of CagA to induce the ubiquitination
      and degradation of RUNX3, thereby extinguishing its ability to inhibit the
      transcriptional activation of RUNX3. Our studies identify RUNX3 as a novel
      cellular target of H. pylori CagA and also reveal a mechanism by which CagA
      functions as an oncoprotein by blocking the activity of gastric tumor suppressor
      RUNX3.

PMID- 20676135
TI  - Phosphorylated p68 RNA helicase activates Snail1 transcription by promoting HDAC1
      dissociation from the Snail1 promoter.
AB  - The nuclear p68 RNA helicase is a prototypical member of the DEAD-box family of
      RNA helicases. p68 RNA helicase has been implicated in cell proliferation and
      early organ development and maturation. However, the functional role of p68 RNA
      helicase in these biological processes at the molecular level is not well
      understood. We previously reported that tyrosine phosphorylation of p68 RNA
      helicase mediates the effects of platelet-derived growth factor (PDGF) in
      induction of epithelial mesenchymal transition by promoting beta-catenin nuclear
      translocation. Here, we report that phosphorylation of p68 RNA helicase at Y593
      upregulates transcription of the Snail1 gene. The phosphorylated p68 activates
      transcription of the Snail1 gene by promoting histone deacetylase (HDAC)1
      dissociation from the Snail1 promoter. Our results showed that p68 interacted
      with the nuclear remodeling and deacetylation complex MBD3:Mi-2/NuRD. Thus, our
      data suggested that a DEAD-box RNA unwindase could potentially regulate gene
      expression by functioning as a protein 'displacer' to modulate protein-protein
      interactions at the chromatin-remodeling complex.

PMID- 20676136
TI  - Accelerated DNA replication in E2F1- and E2F2-deficient macrophages leads to
      induction of the DNA damage response and p21(CIP1)-dependent senescence.
AB  - E2F1-3 proteins appear to have distinct roles in progenitor cells and in
      differentiating cells undergoing cell cycle exit. However, the function of these
      proteins in paradigms of terminal differentiation that involve continued cell
      division has not been examined. Using compound E2F1/E2F2-deficient mice, we have
      examined the effects of E2F1 and E2F2 loss on the differentiation and
      simultaneous proliferation of bone-marrow-derived cells toward the macrophage
      lineage. We show that E2F1/E2F2 deficiency results in accelerated DNA replication
      and cellular division during the initial cell division cycles of bone-marrow
      derived cells, arguing that E2F1/E2F2 are required to restrain proliferation of
      pro-monocyte progenitors during their differentiation into macrophages, without
      promoting their cell cycle exit. Accelerated proliferation is accompanied by
      early expression of DNA replication and cell cycle regulators. Remarkably, rapid
      proliferation of E2F1/E2F2 compound mutant cultures is temporally followed by
      induction of a DNA damage response and the implementation of a p21(CIP1)
      dependent senescence. We further show that differentiating E2F1/E2F2-knockout
      macrophages do not trigger a DNA damage response pathway in the absence of DNA
      replication. These findings underscore the relevance of E2F1 and E2F2 as
      suppressors of hematopoietic progenitor expansion. Our data indicate that their
      absence in differentiating macrophages initiates a senescence program that
      results from enforcement of a DNA damage response triggered by DNA hyper
      replication.

PMID- 20676137
TI  - MOS, aneuploidy and the ploidy cycle of cancer cells.
AB  - After DNA or spindle damage, p53-defective tumor cells undergo a complex cycle of
      reversible polyploidy. How this process occurs and more importantly, why, has
      recently become the focus of several research groups, prompting this review in
      which we discuss two related phenomena that accompany the reversible polyploidy
      of tumor cells: the induction of meiosis genes such as MOS and the decrease in
      genomic instability observed during the reversion from polyploidy to para
      diploidy. The reversible polyploidy likely provides the means through which the
      balance between increased chromosome instability (CIN), driving genetic variation
      and decreased CIN, necessary for perpetuating these malignant clones, is
      maintained. These concepts are integrated with recent findings that many meiotic
      and self-renewal genes become activated during reversible polyploidy and lead us
      to the hypothesis that tumor cell immortality may be achieved through germline
      like transmission.

PMID- 20676138
TI  - Neuropeptide Y and its Y2 receptor: potential targets in neuroblastoma therapy.
AB  - Neuroblastomas are pediatric tumors that develop from sympathetic precursors and
      express neuronal proteins, such as neuropeptide Y (NPY). NPY is a sympathetic
      neurotransmitter acting via multiple receptors (Y1-Y5R). Both NPY and Y2Rs are
      commonly expressed in neuroblastoma cell lines and tissues. The peptide secreted
      from neuroblastomas stimulates tumor cell proliferation and angiogenesis. As both
      processes are Y2R-mediated, the aim of this study was to assess Y2R as a
      potential therapeutic target for neuroblastoma. In vitro, Y2R antagonist
      (BIIE0246) prevented activation of p44/42 mitogen-activated protein kinase (MAPK)
      induced by endogenous NPY, which resulted in decreased proliferation and
      induction of Bim-mediated apoptosis. Similar growth-inhibitory effects were
      achieved with NPY small interfering RNA (siRNA) and Y2R siRNA. In vivo, Y2R
      antagonist significantly inhibited growth of SK-N-BE(2) and SK-N-AS xenografts,
      which was associated with decreased activation of p44/42 MAPK, as well as reduced
      proliferation (Ki67) and increased apoptosis (TdT-mediated dUTP nick end
      labeling; TUNEL). The Y2R antagonist also exerted an antiangiogenic effect. In
      vitro, it reduced the proliferation of endothelial cells induced by neuroblastoma
      conditioned media. Consequently, the Y2R antagonist-treated xenografts had
      decreased vascularization and a high degree of focal fibrosis. In human
      neuroblastoma tissues, the expression of Y2R was observed in both tumor and
      endothelial cells, while NPY was predominantly expressed in neuroblastoma cells.
      In summary, Y2R is a promising new target for neuroblastoma therapy affecting
      both cancer cells and tumor vasculature.

PMID- 20676139
TI  - Cross-talk between PI3K and estrogen in the mouse thyroid predisposes to the
      development of follicular carcinomas with a higher incidence in females.
AB  - It is well known that thyroid disease is more frequent in women than in men;
      however, the molecular basis for this gender-based difference is still poorly
      understood. The activation of phosphoinositide 3-kinase (PI3K), through different
      mechanisms including loss of the PTEN tumor suppressor, is being increasingly
      recognized as a major player in the development of thyroid neoplastic lesions.
      Loss of Pten in the mouse thyroid results in a significant increase in the
      thyrocyte proliferative index, which is more prominent in the female mice. In
      this study, we show that 52% of the Pten(-/-) female mice, but only 12% of the
      males, develop follicular adenomas by 1 year of age. In addition, 50% of female
      mutants, but only 35% of males older than 1 year of age develop invasive, and
      often metastatic, follicular carcinomas. Mutant females have a significantly
      shorter overall survival compared with male mutants. Hormonal manipulation
      experiments established a direct role of estrogens in controlling the increased
      thyrocyte proliferation index in mutant females. Furthermore, while genetic
      ablation of one Cdkn1b allele accelerated the development of neoplastic lesions,
      it also abolished the gender differences in survival and reduced the difference
      in neoplastic lesion development rate, underlining a key role of p27 in mediating
      estrogen action in the thyroid follicular cells. These data, based on a
      clinically relevant model of thyroid follicular carcinoma, provide, to the best
      of our knowledge, for the first time in vivo evidence that circulating estrogens
      are directly responsible for the increased female susceptibility to thyroid
      disease, at least on activation of the PI3K pathway, and provide new insights
      into the gender-based differences characterizing thyroid neoplastic disorders.

PMID- 20676140
TI  - Rb inactivation accelerates neoplastic growth and substitutes for recurrent
      amplification of cIAP1, cIAP2 and Yap1 in sporadic mammary carcinoma associated
      with p53 deficiency.
AB  - Genetically defined mouse models offer an important tool to identify critical
      secondary genetic alterations with relevance to human cancer pathogenesis. We
      used newly generated MMTV-Cre105Ayn mice to inactivate p53 and/or Rb strictly in
      the mammary epithelium, and to determine recurrent genomic changes associated
      with deficiencies of these genes. p53 inactivation led to formation of estrogen
      receptor-positive raloxifene-responsive mammary carcinomas with features of
      luminal subtype B. Rb deficiency was insufficient to initiate carcinogenesis but
      promoted genomic instability and growth rate of neoplasms associated with p53
      inactivation. Genome-wide analysis of mammary carcinomas identified a recurrent
      amplification at chromosome band 9A1, a locus orthologous to human 11q22, which
      contains protooncogenes cIAP1 (Birc2), cIAP2 (Birc3) and Yap1. It is interesting
      that this amplicon was preferentially detected in carcinomas carrying wild-type
      Rb. However, all three genes were overexpressed in carcinomas with p53 and Rb
      inactivation, likely due to E2F-mediated transactivation, and cooperated in
      carcinogenesis according to gene knockdown experiments. These findings establish
      a model of luminal subtype B mammary carcinoma, identify critical role of cIAP1,
      cIAP2 and Yap1 co-expression in mammary carcinogenesis and provide an explanation
      for the lack of recurrent amplifications of cIAP1, cIAP2 and Yap1 in some tumors
      with frequent Rb deficiency, such as mammary carcinoma.

PMID- 20676141
TI  - Adenovirus 5 E1A enhances histone deacetylase inhibitors-induced apoptosis
      through Egr-1-mediated Bim upregulation.
AB  - Histone deacetylase inhibitors (HDACi) are potent anti-cancer agents for variety
      of cancer types. Suberoylanilide hydroxamic acid (SAHA) has been approved as a
      drug to treat cutaneous T cell lymphoma, and the combination of HDACi and other
      agents have been actively tested in many clinical trials. Adenovirus 5 early
      region 1A (E1A) has been shown to exhibit high tumor suppressor activity, and
      gene therapy using E1A has been tested in clinical trials. Here, we showed that
      proapoptotic activity of HDACi was robustly enhanced by E1A in multiple cancer
      cells, but not in normal cells. Moreover, we showed that combination of E1A gene
      therapy and SAHA showed high therapeutic efficacy with low toxicity in vivo
      ovarian and breast xenograft models. SAHA downregulated Bcl-XL and upregulated
      proapoptotic BH3-only protein Bim, whose expression was further enhanced by E1A
      in cancer cells. These alterations of Bcl-2 family proteins were critical for
      apoptosis induced by the combination in cancer cells. SAHA enhanced acetylation
      of histone H3 in Bim promoter region, while E1A upregulated Egr-1, which was
      directly involved in Bim transactivation. Together, our results provide not only
      a novel insight into the mechanisms underlying anti-tumor activity of E1A, but
      also a rationale for the combined HDACi and E1A gene therapy in future clinical
      trials.

PMID- 20676142
TI  - p66(Shc) restrains Ras hyperactivation and suppresses metastatic behavior.
AB  - Normal tissue cells survive and proliferate only while anchored to solid
      substrate. Conversely, transformed cells both survive and proliferate following
      detachment, having lost attachment context through unclear mechanisms. p66(Shc)
      is a focal adhesion-associated protein that reports cell attachment through a
      RhoA-dependent mechanosensory test. We find that human small cell lung cancer
      (SCLC) cells and mouse Lewis lung carcinoma (LLC), which display aggressive
      metastatic behavior, lack both p66(Shc) and retinoblastoma (pRB) and bypass
      anoikis. Re-expression of p66(Shc) in these cells restores anoikis and provides
      striking protection from metastasis by LLC cells in vivo. Notably, knockdown of
      p66(Shc) in normal epithelial cells leads to unrestrained Ras activation,
      preventing anoikis through downstream suppression of RhoA but blocking
      proliferation in a pRB-dependent manner, thus mimicking oncogenic Ras.
      Conversely, LLC and SCLC cells display constitutive Ras activation necessary to
      bypass anoikis, which is reversed by re-expression of p66(Shc). p66(Shc)
      therefore coordinates Ras-dependent control of proliferation and anchorage
      sensation, which can be defeated in the evolution of highly metastatic tumors by
      combined loss of both p66(Shc) and pRB.

PMID- 20676143
TI  - Characterization of DeltaNp73 expression and regulation in gastric and esophageal
      tumors.
AB  - p73 is a member of the p53 protein family. Although the tumor suppressor function
      of p53 is clearly defined, the role of p73 in tumorigenesis is still a matter of
      debate. A complex pattern of expression of p73 isoforms makes it difficult to
      unambiguously interpret the experimental results. Previously, we along with
      others have found that the N-terminally truncated isoform of p73, DeltaNp73, has
      potent anti-apoptotic and oncogenic properties in vitro and in vivo. In this
      study, we analyzed, for the first time, the regulation of DeltaNp73 in a large
      number of gastric, gastroesophageal junction and esophageal tumors. We found that
      expression of DeltaNp73 mRNA and protein is increased in these neoplasms.
      Furthermore, the upregulation of the DeltaNp73 protein is significantly
      associated with poor patient survival. Oncogenic properties of DeltaNp73 were
      further confirmed by finding that DeltaNp73 facilitates anchorage-independent
      growth of gastric epithelial cells in soft agar. As little is currently known
      about the regulation of DeltaNp73 transcription, we investigated the alternative
      p73 gene promoter that mediates the DeltaNp73 expression. Analyzing the DeltaNp73
      promoter in silico as well as by using chromatin immunoprecipitation, site
      directed mutagenesis and deletion analyses, we identified the evolutionary
      conserved region within the DeltaNp73 promoter that contains binding sites for
      HIC1 (hypermethylated in cancer) protein. We found that HIC1 negatively regulates
      DeltaNp73 transcription in mucosal epithelial cells. This leads to a decrease in
      DeltaNp73 protein levels and may normally control the oncogenic potential of the
      DeltaNp73 isoform.

PMID- 20676144
TI  - Cell cycle-dependent acetylation of Rb2/p130 in NIH3T3 cells.
AB  - The retinoblastoma protein (pRb) and the pRb-related proteins, p130 and p107,
      form the 'pocket protein' family of cell cycle regulatory factors. A well
      characterized function of these proteins is the cell cycle-dependent regulation
      of E2F-responsive genes. The biological activity of pocket proteins is regulated
      by phosphorylation and for the founding member pRb it has been shown that
      acetylation also has an important role in modulating its function during the cell
      cycle. Here, we show that hyperphosphorylated retinoblastoma 2 (Rb2)/p130 also
      exists in an acetylated form in NIH3T3 cells. Acetylated p130 is present in the
      nucleus but not in the cytoplasm. Acetylation is cell cycle dependent, starting
      in S-phase and persisting until late G(2)-period. Using recombinant p130 and
      truncated forms for in vitro acetylation by the acetyltransferase p300, we could
      identify K1079 in the C-terminal part as the major acetylation site by mass
      spectrometry. Minor acetylation sites were pinpointed to K1068 and K1111 in the C
      terminus, and K128 and K130 in the N-terminus. The human papilloma virus 16
      protein-E7 preferentially binds to acetylated p130 and significantly increases in
      vitro p130 acetylation by p300.

PMID- 20676146
TI  - Evasion of innate immunity by Mycobacterium tuberculosis: is death an exit
      strategy?
AB  - Virulent Mycobacterium tuberculosis inhibits apoptosis and triggers necrosis of
      host macrophages to evade innate immunity and delay the initiation of adaptive
      immunity. By contrast, attenuated M. tuberculosis induces macrophage apoptosis,
      an innate defence mechanism that reduces bacterial viability. In this Opinion
      article, we describe how virulent M. tuberculosis blocks production of the
      eicosanoid lipid mediator prostaglandin E(2) (PGE(2)). PGE(2) production by
      infected macrophages prevents mitochondrial damage and initiates plasma membrane
      repair, two processes that are crucial for preventing necrosis and inducing
      apoptosis. Thus, M. tuberculosis-mediated modulation of eicosanoid production
      determines the death modality of the infected macrophage, which in turn has a
      substantial impact on the outcome of infection.

PMID- 20676145
TI  - The biofilm matrix.
AB  - The microorganisms in biofilms live in a self-produced matrix of hydrated
      extracellular polymeric substances (EPS) that form their immediate environment.
      EPS are mainly polysaccharides, proteins, nucleic acids and lipids; they provide
      the mechanical stability of biofilms, mediate their adhesion to surfaces and form
      a cohesive, three-dimensional polymer network that interconnects and transiently
      immobilizes biofilm cells. In addition, the biofilm matrix acts as an external
      digestive system by keeping extracellular enzymes close to the cells, enabling
      them to metabolize dissolved, colloidal and solid biopolymers. Here we describe
      the functions, properties and constituents of the EPS matrix that make biofilms
      the most successful forms of life on earth.

PMID- 20676147
TI  - GVHD after unrelated cord blood transplant in children: characteristics,
      severity, risk factors and influence on outcome.
AB  - We reviewed our experience in 79 children who had unrelated cord blood transplant
      (UCBT) between 1996 and 2007 with a major focus on GVHD, comparing both
      traditional and National Institute of Health (NIH) criteria. The cumulative
      incidence (CI) of acute GVHD (aGVHD, by day +100) was 0.42 for grade II-IV and
      0.22 for grade III-IV. The CI of all aGVHD (NIH, that is, no time limit) at 1
      year was 0.45 for grade II-IV and 0.32 for grade III-IV. Infused CD34 cell dose
      (>1 * 10(5)/kg), pretransplant bacterial infection and nonmalignant disorders
      were risk factors for grade II-IV aGVHD on univariate analysis. Infused CD34 cell
      dose remained significant on multivariate analysis. At 1 year, the CI of chronic
      GVHD (cGVHD) using the Seattle criteria was 0.27, whereas that for cGVHD (NIH)
      was 0.08. By NIH criteria, the classic form of cGVHD was uncommon (5%) after
      UCBT. Instead, the acute (71%) and overlap (24%) GVHD variants predominated.
      Grade II-IV aGVHD was a significant risk factor for cGVHD by both Seattle and NIH
      criteria. We conclude that GVHD after day +100 after UCBT typically carries
      features of aGVHD. Moreover, and in marked contrast to adult unrelated donor
      hematopoietic stem cell transplantation, the GVHD observed in this series did not
      adversely affect survival.

PMID- 20676148
TI  - Sustained CR of refractory aggressive natural killer cell leukemia following
      unrelated cord blood transplantation.

PMID- 20676149
TI  - Bortezomib added to high-dose melphalan as pre-transplant conditioning is safe in
      patients with heavily pre-treated multiple myeloma.

PMID- 20676150
TI  - Successful mobilization of PBSCs in a healthy volunteer donor by addition of
      plerixafor after failure of mobilization with G-CSF alone.

PMID- 20676151
TI  - Next generation eye surgery and drug delivery.

PMID- 20676152
TI  - Canadian blind sport: participation and excellence.

PMID- 20676153
TI  - Canadian Ophthalmological Society policy statement on the medical use of
      marijuana for glaucoma.

PMID- 20676154
TI  - A longitudinal study of reproductive performance and management of 82 dairy herds
      in the Waikato region with differing policies on the routine use of induction of
      parturition.
AB  - AIMS: To describe the reproductive performance and management practices over
      three lactations in dairy herds that had different policies on the routine use of
      induction of parturition; to describe any change in outcomes in herds that ceased
      inductions during the study period; and to investigate other herd-level factors
      associated with reproductive performance. METHODS: From 2002 to 2004 inclusive, a
      longitudinal study was undertaken in 82 herds in the Waikato region of New
      Zealand. The main outcome variables were the percentage of cows pregnant after 8
      weeks of mating (8-week in-calf rate) and the percentage of cows not pregnant at
      the end of mating (final empty rate). Data were obtained from pregnancy diagnosis
      records from a veterinary practice and from an electronic database, and a
      questionnaire. Herds were classified as either not using inductions in the three
      lactations (Nil; n=14), ceased inductions in the second or third lactation
      (Transitional; n=12), or continuing to induce (Continuing; n=56). RESULTS: Nil
      herds had a higher 8-week in-calf rate (p=0.01) than Transitional or Continuing
      herds (83%, 78% and 79%, respectively). The final empty rate in Nil and
      Transitional herds was similar (10.2% and 9.9%), tended to be greater in Nil than
      in Continuing herds (10.2% vs 9.0%; p=0.06) and was greater in Transitional than
      in Continuing herds (9.9% vs 9.0%; p=0.04), respectively. Multivariable modelling
      found that 8-week in-calf rates were additionally associated with year of
      lactation, interval from the planned start of calving (PSC) to the median calving
      date, duration of artificial insemination, and 21-day submission rate; and that
      final empty rates were associated with year of lactation, predominant breed,
      percentage of the herd calving within 40 days of the planned start of mating
      (PSM), the total duration of mating, and the 21-day submission rate, but not the
      herd induction policy. A change to ceasing routine use of induction tended to be
      associated (p=0.07) with a 2.5% increase in the final empty rate in the lactation
      of change. CONCLUSIONS: The reproductive performance of herds was associated with
      induction policy, in addition to other factors. Herds that ceased induction had a
      greater 8-week in-calf rate but a greater final empty rate than those that
      continued. The higher empty rate in Nil herds was partly due to their shorter
      duration of mating. CLINICAL RELEVANCE: Herdowners and their advisors planning to
      cease routine use of induction should plan for an increase in the final empty
      rate in both the lactation of change and in the longer term, and undertake
      measures to mitigate against this effect.

PMID- 20676155
TI  - Regional seroprevalence of leptospirosis on deer farms in New Zealand.
AB  - AIM: To undertake a seroprevalence survey to estimate the distribution of
      infection by Leptospira spp. serovars Hardjobovis, Pomona and Copenhageni in
      farmed deer herds regionally throughout New Zealand. METHODS: Between March 2003
      and February 2005, 111 red and red x wapiti deer herds not using a leptospiral
      vaccine were selected from nine regions from Northland to Southland. Eighty-three
      herds were selected for on-farm collection of 12-20 blood samples from hinds
      predominantly 9-30 months of age, by jugular venepuncture, while similar numbers,
      predominantly males 9-30 months of age, per farm were collected from 28 herds at
      sticking at deer slaughter premises (DSP). Serum was stored frozen until analysed
      using the microscopic agglutination test (MAT). Titre cut-points of 1:24 for
      serovar Hardjobovis and 1:48 for serovars Pomona and Copenhageni were considered
      positive at the individual animal level. Herds were considered seropositive if
      there were at least three animals per herd seropositive to any serovar. RESULTS:
      Eighty-one percent of herds were seropositive for Leptospira spp. Hardjobovis was
      the predominant serovar at the herd (78%) and individual animal (60.8%) levels.
      The seroprevalence of Pomona was 20% and 8.4% at the herd and animal levels,
      respectively. Dual seroreactivity to both Hardjobovis and Pomona was observed in
      16% of herds and 6.6% of individuals; within-herd seroprevalence for both
      serovars ranged from 0 to 100%. No herds and 1.2% of animals were seropositive
      for serovar Copenhageni. There was a regional difference in the prevalence of
      herds seropositive to both Hardjobovis and Pomona (p=0.02), but no difference
      between regions in the prevalence of herds seropositive to either Hardjobovis or
      Pomona alone. CONCLUSION: The seroprevalence of Leptospira spp. serovars is high,
      and distributed in farmed deer herds throughout New Zealand. CLINICAL
      SIGNIFICANCE: Results confirm the risk of disease and potential loss of
      production in deer, and exposure of infection to humans and other livestock from
      deer is widespread, demonstrating that control of the disease needs to be
      considered at a national rather than regional level.

PMID- 20676156
TI  - Reduction in the incidence of elbow dysplasia in four breeds of dog as measured
      by the New Zealand Veterinary Association scoring scheme.
AB  - AIM: To determine if there has been any reduction in the incidence of elbow
      dysplasia in four popular large-dog breeds as measured by the New Zealand
      Veterinary Association (NZVA) scoring scheme. METHODS: A retrospective analysis
      of the NZVA elbow dysplasia database was performed using records of all German
      Shepherd dogs, Labrador Retrievers, Golden Retrievers and Rottweilers that had
      undergone evaluation since the scheme's inception in 1992. The data for each dog
      included date of birth, date of radiography, gender, grade of left and right
      elbow (0, 1, 2 or 3), and accredited or dysplastic status. Ordinal logistic
      regression was used to model the grade of the worst-affected elbow over time. The
      model included age at scoring and gender as additional variables. Given the known
      heritability of elbow dysplasia, the hypothesis was that if the NZVA scheme
      effectively identifies elbow dysplasia, and that dog breeders have been using the
      data responsibly, there should have been a trend towards a lower incidence of
      dogs graded dysplastic over time. RESULTS: In all four breeds, there was a
      significant trend towards lower grades of the worst-affected elbow over time. For
      German Shepherd dogs the incidence of elbow dysplasia (worst elbow grade not
      zero) fell from 75% to 47% between dogs born in 1991 vs those born in 2008. The
      corresponding figures were a drop from 86% to 68% for the Labrador Retriever,
      from 89% to 77% for Golden Retrievers, but only 98% to 95% for Rottweilers. In
      the Rottweiler and Golden Retriever, gender had a significant effect on the worst
      elbow grade. In the Golden Retriever, age at scoring also had a significant
      effect. CONCLUSIONS: There has been a significant reduction in the incidence of
      elbow dysplasia in four popular large-dog breeds as scored by the NZVA elbow
      dysplasia scoring scheme. The limitations of the study are the non-compulsory
      nature of the elbow dysplasia scheme, and the potential bias caused by dog
      breeders or veterinarians pre-screening potential submissions. The results
      therefore may not represent those of the overall population. CLINICAL RELEVANCE:
      The incidence of elbow dysplasia, as measured by the NZVA elbow dysplasia scheme,
      has reduced in the four breeds investigated since the scheme's inception. The New
      Zealand Kennel Club (NZKC) and the veterinary profession can confidently support
      the NZVA scoring scheme, and should promote its use by dog breeders.

PMID- 20676157
TI  - The effect of zinc oxide and elemental zinc boluses on the concentrations of Zn
      in serum and faeces, and on providing protection from natural Pithomyces
      chartarum challenge in calves.
AB  - AIM: To investigate the efficacy of intra-ruminal Zn boluses as aids in providing
      protection from natural Pithomyces chartarum challenge in calves. METHODS: Sixty
      two calves (mean weight 187 (SEM 3.25) kg) were divided into three groups.
      Commencing on Day 0, they received either a proprietary bolus containing 83% ZnO
      (ZnO group), a prototype Zn bolus containing 88% elemental Zn (Zn group), or
      remained untreated (Control group). Concentrations of Zn in serum and faeces were
      measured weekly between Days 6 and 34, activities of gamma-glutamyl transferase
      (GGT) in serum on Days -8, 20, 34 and 41, and faecal spore counts between Days 13
      and 41. RESULTS: Between Days 6 and 34, mean concentrations of Zn in serum
      increased in both Zn treatment groups compared with Controls (p<0.001), but were
      lower in Zn than ZnO animals between Days 6 and 28 (p=0.05). Concentrations of Zn
      in faeces were increased in both groups following treatment with Zn. Mean
      concentrations of Zn in faeces in ZnO animals was higher than Zn animals on Days
      13 and 20 (p<0.001), but decreased by Day 34, whereas for Zn animals they were
      still elevated on Day 34. Faecal spore counts were 354,000 and 183,000 on Days 13
      and 20, respectively, 610,500 on Day 28, and 115,500 spores/g on Day 34. There
      were no clinical signs of facial eczema, but based on the activities of GGT on
      Day 41, 17/20 (85%) Controls were moderately or severely affected (GGT >250 IU/L)
      compared with 1/21 (5%) ZnO and 3/21 (14%) Zn animals. Mean activities of GGT on
      Day 41 for ZnO and Zn animals were not different (35 (95% CI=23-54) and 54 (95%
      CI=32-92) IU/L, respectively; p=0.18), but were below those of the Controls (502
      (95% CI=296-850) IU/L), confirming efficacy of both bolus treatments. In both ZnO
      and Zn animals, there was no significant relationship between concentration of Zn
      in serum and activity of GGT, but in Zn animals there was a significant
      relationship between the concentration of Zn in faeces and activity of GGT 21
      days later. The regression equation y=2.136-0.002197x (where y is log10GGT
      activity, and x the concentration of Zn in faeces) provided an estimate of the
      threshold level of concentration of Zn in faeces. CONCLUSION: The study confirmed
      efficacy of elemental Zn boluses in providing protection from natural P.
      chartarum challenge in young cattle.

PMID- 20676158
TI  - The effect of zinc oxide and elemental zinc boluses on the concentrations of Zn
      in serum and faeces, and on providing protection from natural Pithomyces
      chartarum challenge in sheep.
AB  - AIM: To investigate the efficacy of intra-ruminal Zn boluses as aids in providing
      protection from natural Pithomyces chartarum challenge in sheep. METHODS: Seventy
      two adult sheep (mean weight 59 (SEM 0.5) kg) were divided into four groups.
      Commencing on Day 0, they received either a proprietary bolus containing 67 g ZnO
      (equivalent to 54 g Zn) (ZnO group), two different levels of elemental Zn (81 and
      108 g) delivered in boluses each containing 27 g Zn (Zn81 and Zn108 groups,
      respectively), or remained untreated (control). Concentrations of Zn in serum,
      activities of gamma-glutamyl transferase (GGT) in serum, and spore counts on
      pasture were measured weekly from Day -6, and concentrations of Zn in faeces
      weekly from Day 21, until Day 77. RESULTS: Mean concentrations of Zn in serum
      between Days 14 and 42 were significantly higher in ZnO animals (15.4 (SEM 0.70)
      micromol/L) than the other groups. Mean concentrations in Zn108 animals (11.1
      (SEM 0.26) micromol/L) were significantly higher than controls, but there were no
      differences between Zn81 and the controls (9.9 (SEM 0.20) and 9.4 (SEM 0.26)
      micromol/L, respectively). Between Days 21 and 49, there was no significant
      difference in mean concentrations of Zn in faeces between ZnO and Zn81 animals
      (307 (SEM 28) and 281 (SEM 29) mg/kg fresh weight (FW), respectively), but
      concentrations were significantly higher in Zn108 animals (500 (SEM 40) mg/kg
      FW). Spore counts exceeded 70,000/g on Days 14, 28, 49, 56 and 63 but there were
      no clinical signs of facial eczema. In controls, activities of GGT were unchanged
      until Day 21, then increased to 637 IU/L at Day 70; for ZnO animals, activities
      remained <75 IU/L until Day 14, then increased to 200 IU/L at Day 70; for Zn81
      and Zn108, they remained <75 IU/L until Day 35, and then increased at Day 70 to
      369 IU/L and 293 IU/L, respectively. From Day 56 activities were significantly
      lower in all treated groups compared with controls, but there was no significant
      difference between the three Zn bolus treatments. There were significant negative
      correlations between activities of GGT and concentrations of Zn in serum in Zn108
      animals, and with concentrations of Zn in faeces for both Zn81 and Zn108 groups.
      CONCLUSION: Elemental Zn boluses can reduce activities of GGT associated with
      elevated spore counts. The association between concentrations of Zn in faeces and
      activities of GGT suggests that a minimum concentration of Zn in the
      gastrointestinal tract may be important in providing protection against
      sporidesmin.

PMID- 20676159
TI  - Analysis of the value of measurement of the activity of caeruloplasmin as an
      alternative to measurement of the concentration of elemental copper in plasma and
      serum of farmed red deer.
AB  - AIM: To evaluate the relationship between the concentration of elemental Cu and
      activity of caeruloplasmin (CP) in the plasma and serum of farmed red deer
      (Cervus elaphus). METHODS: Paired serum and heparinised plasma samples taken from
      142 deer from 10 herds in the North Island of New Zealand were tested for the
      concentration of elemental Cu and activity of CP. Additionally, liver biopsy
      samples were taken from 49 of the deer (all one herd). The relationship between
      individual results for the concentration of elemental Cu and activity of CP was
      examined using a segmented model, with random slope and intercept and threshold.
      RESULTS: The activity of CP in plasma and that in serum were strongly correlated
      (R2=0.994), with a high level of agreement. The concentration of Cu and activity
      of CP also showed a strong association (R2>0.88 for both plasma and serum),
      although there were significant differences between herds, with the segmented
      regression model providing the best fit rather than a linear mixed model. Using
      the current thresholds for elemental Cu, the relationship between the
      concentration of Cu and activity of CP suggested that an activity of CP of <4
      IU/L indicates Cu deficiency, and that deer with an activity of CP of >or=7 IU/L
      have adequate Cu status. CONCLUSIONS: The relationship between elemental Cu and
      CP is markedly different from the simple linear relationship previously reported
      for cattle. Above a threshold of 10 IU/L, the rise in elemental Cu per unit
      increase in activity of CP was 50% of that below 10 IU/L. This is probably
      because above this threshold the oxidative activity of CP per enzyme unit was
      greater. CLINICAL RELEVANCE: The association between concentration of Cu and
      activity of CP was robust enough to define provisional thresholds for determining
      Cu status. However, the proximity of the deficiency threshold to the limit of
      detection of the CP test, the effect of herd on the association, and the inherent
      disadvantages of using an enzymatic system, mean that activity of CP should not
      be used routinely to estimate Cu status in deer. When assessing the Cu status of
      deer based on blood samples, the concentration of Cu in plasma or serum should be
      used.

PMID- 20676160
TI  - Public awareness in New Zealand of animal welfare legislation relating to cats.
AB  - AIMS: To ascertain the levels of awareness of legislation governing the welfare
      of cats, and provision of basic care, including vaccination, by cat owners within
      two locations in New Zealand. To assess the ability of respondents to
      differentiate between the terms 'stray' and 'feral'. METHODS: A face-to-face
      questionnaire, consisting of 12 questions in three sections, was distributed by
      volunteers within Auckland (n=255) and Kaitaia (n=99) to gather information
      pertinent to the study's aims. Section 1 covered respondents' personal details;
      Section 2, ownership and care of cats, including whether or not the cats were
      vaccinated against feline immunodeficiency virus (FIV) and feline leukaemia virus
      (FeLV); and Section 3, awareness of legislation and differences between the terms
      'stray' and 'feral'. RESULTS: Overall, fewer than half of respondents were aware
      of the animal welfare legislation within New Zealand or the semantic differences
      between the terms 'stray' and 'feral' as they appear in the dictionary.
      Respondents >or=41 years old, and individuals employed in the animal-related
      sector, were significantly more likely to be aware of the legislation and make
      the correct distinction between the terms compared with those aged <or=40, and
      those working in a non-animal-related profession. A significantly greater
      percentage of cat owners (42%) provided care for cats they did not own compared
      with non-owners (26%). Results also indicated a large majority of cat owners may
      consider standard annual vaccinations to include vaccination against FIV and
      FeLV. CONCLUSION: Dissemination of information about animal welfare legislation
      is important for the care of cats within New Zealand, and the definitions of the
      terms 'stray' and 'feral' need to be more clearly stated in order to prevent
      confusion. This is especially important when cats may be controlled using lethal
      measures under different legislative precedents that are not necessarily
      consistent with one another. CLINICAL RELEVANCE: Veterinary clinics may act as a
      primary source for the dissemination of information about relevant welfare acts
      as well as preventative health care, thus improving the welfare of cats. Cat
      owners need to be better educated about the diseases covered by annual
      vaccination.

PMID- 20676161
TI  - Concurrent avian malaria and avipox virus infection in translocated South Island
      saddlebacks (Philesturnus carunculatus carunculatus).
AB  - CASE HISTORY: Outbreaks of mortality in South Island saddlebacks (Philesturnus
      carunculatus carunculatus) that had been translocated to two offshore islands in
      the Marlborough Sounds of New Zealand were investigated during the summers of
      2002 and 2007. Both outbreaks were associated with a severe decrease in numbers
      of saddlebacks of up to 60% of approximately 200 birds. CLINICAL AND PATHOLOGICAL
      FINDINGS: Many of the surviving birds were in poor condition, and had skin
      lesions on the legs and head. Necropsy showed pale liver and lungs, and a swollen
      spleen. Histopathology revealed schizonts resembling Plasmodium spp. within the
      cytoplasm of many hepatocytes and splenic histiocytes. The skin lesions consisted
      of epithelial proliferations containing numerous Bollinger bodies typical of
      avipox virus (APV) infection. Two different APV were isolated, using PCR, from
      two different birds exhibiting skin lesions. Each isolate had 100% sequence
      homology with APV members from either Clade A or Clade B. In addition, PCR
      analysis revealed that the Plasmodium elongatum present in infected birds
      belonged to a strain that was endemic in the population of North Island
      saddlebacks (Philesturnus carunculatus rufusater). DIAGNOSIS: Concurrent
      infections with Plasmodium spp. haemoparasites and APV were identified as the
      likely cause of death in the birds examined. CONCLUSIONS AND CLINICAL RELEVANCE:
      Although the Plasmodium spp. identified is thought to be endemic to saddlebacks
      in New Zealand, the affected birds were likely to be immunocompromised by
      concurrent APV infection or through lack of genetic diversity. Both the
      introduced mosquito Culex quinquefasicatus and the native mosquito Culex
      pervigilans are likely vectors for both these diseases, and the provision of
      water supplies less favourable to mosquito-breeding is recommended.

PMID- 20676162
TI  - Superimposing acceleration and optimization method of optical reconfiguration
      speed without any increase of laser power.
AB  - This paper proposes a method of superimposing acceleration and optimizing the
      optical reconfiguration speed while requiring no increase of laser power. Using
      this technique, the optical reconfiguration speed is increased by superimposing
      multiple configuration contexts. Simultaneously, optimization of the number of
      configuration contexts and reconfiguration speed is possible. A full four-context
      optically reconfigurable gate array system consisting of an optically
      reconfigurable gate array VLSI, an easily rewritable liquid crystal holographic
      memory, and four vertical-cavity surface-emitting lasers was constructed to
      demonstrate this method. This paper clarifies the method's benefits using
      experimental results obtained from the demonstration system.

PMID- 20676163
TI  - Enhancing coupling efficiency and propagating length for surface plasmon
      polaritons.
AB  - A high coupling efficiency and long propagating length technique is suggested for
      surface plasmon polaritons (SPPs). An attenuated total reflection (ATR) mode is
      employed to enhance the coupling efficiency by SPPs resonating with the incident
      light in the SPP launching zone. In the SPP transmitting zone, a step-metal film
      is embedded in a dielectric to decrease the radiation and absorption losses.
      Simulated results reveal that an SPP transmitting length of several hundred
      micrometers can be achieved with high energy. Besides, analyzed results indicate
      that the fabrication of the device is easy because of its simple structure and
      large tolerances.

PMID- 20676164
TI  - Comparative investigation on performance of acousto-optically Q-switched dual-rod
      Nd:YAG-Nd:YVO(4) laser and dual-rod Nd:YVO(4)-Nd:YVO(4) laser.
AB  - We demonstrated an acousto-optically (AO) Q-switched dual-rod laser with
      different gain crystals in the cavity, the combination of Nd:YAG crystal and
      Nd:YVO(4) crystal. An AO Q-switched dual-rod Nd:YVO(4)-Nd:YVO(4) laser was also
      configured for comparative investigation. A 69 and 75?W near diffraction-limited
      laser in CW operation was obtained for the dual-rod Nd:YAG-Nd:YVO(4) laser and
      dual-rod Nd:YVO(4)-Nd:YVO(4) laser, respectively. In the Q-switched operation,
      500?kHz output with 64.2?W average power and 650?kHz laser with 73.2?W average
      power was achieved for the Nd:YAG-Nd:YVO(4) laser and Nd:YVO(4)-Nd:YVO(4) laser,
      respectively. The detailed comparison on the performance of pulse duration, pulse
      repetition rate, output power, and optical spectrum was also investigated and
      discussed.

PMID- 20676165
TI  - Photodarkening-induced increase of fiber temperature.
AB  - We examine the effect of photodarkening-induced pump light absorption on Yb-doped
      fiber thermal loading. In these experiments, the fiber is cladding pumped at
      915nm, air cooled by natural convection, and monitored with a midinfrared thermal
      camera. The fiber temperature is found to correlate with progressive
      photodarkening. The maximum observed fiber temperature was 120 degrees C,
      recorded at a pump power of 10.5W. The observed increase in fiber temperature can
      be explained by a model that takes into account the combined effects of the Yb
      silica quantum defect, the temperature dependence of the Yb-absorption cross
      section, and photodarkening-induced loss at 915nm. We hypothesize that the latter
      effect results in the progressive activation of temperature-dependent
      photochemical processes (e.g., bleaching) and is an important consideration with
      regard to the accurate modeling of Yb-doped fiber photodarkening kinetics.

PMID- 20676166
TI  - Neural network model for rotation invariant recognition of object shapes.
AB  - A multichannel, multilayer feed forward neural network model is proposed for
      rotation invariant recognition of objects. In the M channel network, each channel
      consists of a one dimensional slice of the two dimensional (2D) Fourier transform
      (FT) of the input pattern that connects fully to the weight matrix. Each slice is
      taken at different angles from the 2D FT of the object. From each channel, only
      one neuron can fire in the presence of the training object. The output layer sums
      up the response of the hidden layer neuron and confirms the presence of the
      object. Rotation invariant recognition from 0 degrees to 360 degrees is obtained
      even in the case of degraded images.

PMID- 20676167
TI  - Use of Monte Carlo simulations for propagation of light in biomedical tissues.
AB  - In problems relating to light propagation in biomedical tissues, the tissue is
      generally modeled as a turbid medium and Monte Carlo (MC) simulation is employed
      to compute quantities such as diffuse reflectance, fluence, and transmittance.
      Two prescriptions are available in the literature for MC simulations. The first
      prescription considers all input quantities, including phase function, as an
      average over the particle size distribution, and the second prescription
      considers the phase function of each scatterer individually. The two
      prescriptions have been compared and contrasted in this paper for a given soft
      tissue model. It is demonstrated that, in general, the two recipes do not yield
      identical results. The source of this disagreement has been traced.

PMID- 20676168
TI  - Simple analytical derivations of thermal lensing in longitudinally Q-CW pumped
      Yb:YAG.
AB  - In this paper, we introduce analytical derivations for the thermal lensing of an
      end-pumped laser disk. These derivations are done for pump beam shapes from
      Gaussian to top hat, assuming that the thermal conductivity is either constant
      with the temperature or not. We give examples in two temperature regions, where
      the thermal conductivity exhibits T(-1) or T(-2) dependence. Numerical
      applications are given for a Q-CW pumped Yb:YAG disk laser.

PMID- 20676169
TI  - Pointing error due to temperature distribution of SiC reflectors in
      intersatellite laser communications.
AB  - Wave-front aberrations due to thermal deformation of elliptical reflectors in
      periscopic laser communication terminals are studied, and are fitted by Zernike
      elliptical polynomials. The relationship between pointing error and temperature
      distribution of elliptical reflectors in intersatellite laser communication
      systems is researched. The back-fixing method is introduced for fixing the
      elliptical reflectors, and is proven to reduce pointing error compared to the
      traditional around-fixing method using a press board. It is shown that the
      difference between uniform temperature and reference temperature has a much
      stronger influence than the temperature gradient. For the back-fixing method, the
      pointing error changes periodically as the uniform temperature changes with a
      period value of 1.6 degrees C, and the maximum pointing error value is 16.7murad.
      The result also tells us that, if the difference between uniform temperature and
      reference temperature is within 1.0 degrees C, there is no pointing error caused
      by back-fixed reflectors. We hope this work can contribute to the thermal control
      of elliptical reflectors in intersatellite laser communication terminals.

PMID- 20676170
TI  - Fabrication and characterization of sandwiched optical fibers with periodic
      gratings.
AB  - This study proposes a novel process for fabricating a sandwiched long-period
      fiber grating (SLPFG) using a SU-8 thick photoresist technique. The SLPFG
      consists of a thin cladding optical fiber sandwiched with a double-sided
      periodical grating coating. By varying the external loads on the SLPFG, the
      transmission dip of the resonance wavelength is tuned according to a squared
      harmonic curve. The SLPFG can thus be utilized as a loss tunable filter or
      sensor. The resonance dip wavelength is related to the cladding thicknesses of
      the optical fiber and the periods of the grating. A maximum transmission resonant
      dip of 34.61dB was achieved.

PMID- 20676171
TI  - Optical design of automotive headlight system incorporating digital micromirror
      device.
AB  - In recent years, the popular adaptive front-lighting automobile headlight system
      has become a main emphasis of research that manufacturers will continue to focus
      great efforts on in the future. In this research we propose a new integral
      optical design for an automotive headlight system with an advanced light-emitting
      diode and digital micromirror device (DMD). Traditionally, automobile headlights
      have all been designed as a low beam light module, whereas the high beam light
      module still requires using accessory lamps. In anticipation of this new concept
      of integral optical design, we have researched and designed a single optical
      system with high and low beam capabilities. To switch on and off the beams, a DMD
      is typically used. Because DMDs have the capability of redirecting incident light
      into a specific angle, they also determine the shape of the high or low light
      beam in order to match the standard of headlight illumination. With collocation
      of the multicurvature reflection lens design, a DMD can control the light energy
      distribution and thereby reinforce the resolution of the light beam.

PMID- 20676172
TI  - Optomechanical shape analysis using group theory.
AB  - We describe an optomechanical technique using a knife-edge, which is scanned
      spatially across a beam of light to identify shape-based irradiance. Symmetry
      groups are identified through linear and rotational scanning signatures of
      illuminated shapes. The scanning signature is used to classify the shape into a
      symmetry group. To demonstrate the shape analysis technique, we have classified
      basic geometric shapes, which belong to the orthogonal and dihedral symmetry
      groups O(2), D(2), D(3), and D(6).

PMID- 20676173
TI  - Microscope spectrometer for light scattering investigations.
AB  - We describe a setup including a microscope to study volumes of a few mum(3) by
      static and dynamic light scattering (DLS) in a backscattering configuration.
      Light scattered by individual objects of micrometric size can be analyzed in the
      400-800?nm spectral range. This setup can also be employed to study both diluted
      and concentrated colloidal solutions by DLS measurements. For diluted solutions
      we found evidence of the fluctuations of the number of particles in a confocal
      volume. We discuss their contribution to the autocorrelation function of the
      scattered intensity measured as a function of time.

PMID- 20676174
TI  - Intense violet-blue-emitting Ba(2)AlB(4)O(9)Cl:Eu(2+) phosphors for applications
      in fluorescent lamps and ultraviolet-light-emitting diodes.
AB  - We synthesized a violet-blue phosphor Ba(2)AlB(4)O(9)Cl:Eu(2+) with a solid-state
      reaction. The excitation and emission spectra of this phosphor showed that all
      were broadband due to 4f(7)-4f(6)d(1) transitions of Eu(2+). The phosphors with
      different Eu(2+) concentrations presented violet-blue luminescence for
      ultraviolet [(UV) 250-390nm] excitation. The optimum concentration of Eu(2+) in
      Ba(2)AlB(4)O(9)Cl:Eu(2+) is determined to be 6mol.%. The luminous efficiency was
      found to be 8.1lm/W for the violet-blue fluorescent lamp and 3.2lm/W for the
      violet-blue phosphor-converted light-emitting diode, respectively.
      Ba(2)AlB(4)O(9)Cl:Eu(2+) would be a promising phosphor for converting the UV
      radiation to violet-blue emission for a novel high light-conversion efficiency
      phototherapy illuminator.

PMID- 20676175
TI  - Modeling the field diffracted from photo mask at oblique incidence.
AB  - In optical lithography, light diffracted from photo mask structures has been
      customarily assumed to be constant with the angle of incidence of the light
      illuminating the photo mask. As numerical aperture increases to unity and beyond,
      to cope with the continuous demand for shrinking integrated circuits, device
      dimensions, and densities, this approximation is no longer valid. In this paper
      we use the physical theory of diffraction to study, understand, and model the
      variation of light diffracted from photo mask structures of the order of the
      wavelength, with the angle of light incidence. We present a semianalytical model
      that is fast, accurate, and compatible with existing professional software in
      this domain. The accuracy of the model is studied using the finite-difference
      time-domain technique and is shown to be below 5% at the image plane, within
      angles of incidence between +/-20 degrees .

PMID- 20676176
TI  - Spontaneous Rayleigh-Brillouin scattering of ultraviolet light in nitrogen, dry
      air, and moist air.
AB  - Atmospheric lidar techniques for the measurement of wind, temperature, and
      optical properties of aerosols rely on the exact knowledge of the spectral line
      shape of the scattered laser light on molecules. We report on spontaneous
      Rayleigh-Brillouin scattering measurements in the ultraviolet at a scattering
      angle of 90 degrees on N(2) and on dry and moist air. The measured line shapes
      are compared to the Tenti S6 model, which is shown to describe the scattering
      line shapes in air at atmospheric pressures with small but significant
      deviations. We demonstrate that the line profiles of N(2) and air under equal
      pressure and temperature conditions differ significantly, and that this
      difference can be described by the S6 model. Moreover, we show that even a high
      water vapor content in air up to a volume fraction of 3.6vol.% has no influence
      on the line shape of the scattered light. The results are of relevance for the
      future spaceborne lidars on ADM-Aeolus (Atmospheric Dynamics Mission) and
      EarthCARE (Earth Clouds, Aerosols, and Radiation Explorer).

PMID- 20676177
TI  - Extraction of phase derivative data from interferometer images using a continuous
      wavelet transform to determine two-dimensional refractive index profiles.
AB  - Two-dimensional refractive index profiles of ion exchanged channel waveguides in
      glass have been obtained from the analysis of interferometer data. To obtain
      depth data, a shallow bevel is produced in the glass by polishing. The refractive
      index profile information that is contained within the derivative of the phase
      data is extracted directly using a continuous wavelet transform algorithm. The
      algorithm used to characterize and smooth the wavelet ridge is discussed in
      detail.

PMID- 20676178
TI  - Nonsequential modeling of laser diode stacks using Zemax: simulation,
      optimization, and experimental validation.
AB  - Modeling a real laser diode stack based on Zemax ray tracing software that
      operates in a nonsequential mode is reported. The implementation of the model is
      presented together with the geometric and optical parameters to be adjusted to
      calibrate the model and to match the simulated intensity irradiance profiles with
      the experimental profiles. The calibration of the model is based on a near-field
      and a far-field measurement. The validation of the model has been accomplished by
      comparing the simulated and experimental transverse irradiance profiles at
      different positions along the caustic formed by a lens. Spot sizes and waist
      location are predicted with a maximum error below 6%.

PMID- 20676179
TI  - Structural optimization for broadband scattering in several ultra-thin white
      beetle scales.
AB  - Recent work discovered the remarkable optical scattering properties of the scales
      of the white beetle Cyphochilus. It was suggested that its brilliant whiteness
      and brightness were due to optimization of the microstructure within its scales.
      Here we compare the microstructure of Cyphochilus scales to those of two other
      white beetles, Lepidiota stigma and Calothyrza margaritifera. Extensive optical
      modeling and experimental data suggest that each species displays structural
      optimization designed to maximize optical scatter. Optimization of the scale
      filling fraction is observed, as well as optimization of scattering center
      spacing and diameter. Cyphochilus, in particular, displays a high degree of
      structural optimization, resulting in its bright white appearance.

PMID- 20676180
TI  - Formation of holographic memory for defect tolerance in optically reconfigurable
      gate arrays.
AB  - Holographic polymer-dispersed liquid-crystal (HPDLC) memory using liquid-crystal
      composites is proposed for new optical information processing. Formation of HPDLC
      memory using a photomask is discussed for parallel programmability to realize
      fast reconfiguration of optically reconfigurable gate arrays (ORGAs). The defect
      tolerance of HPDLC memory is investigated to clarify the defect limitation of
      holographic configurations using ORGAs. Experimental results show that the noise
      ratio less than 15% applied to HPDLC memory rarely affects its diffraction
      pattern or a reconfiguration context.

PMID- 20676181
TI  - Plasmonic multimode waveguides with transversely structured core.
AB  - We analyze the propagation of surface plasmons in metallic multimode waveguides
      that consist of alternating stripes of different metals in the transverse
      direction and that are homogeneous in the longitudinal direction. The purpose of
      structuring the waveguide in the transverse direction is to take advantage of the
      different attenuation and propagation constants for different metals. Here, in
      particular, alternating stripes of Ag and Au are considered. This allows one to
      influence the modal spectrum. We consider two different, well-defined waveguide
      configurations. For these, the propagating plasmonic modes are calculated. Based
      on the numerical simulations, we discuss the attenuation and propagation behavior
      and show the resulting eigenmodes for different values of the structural
      parameters, i.e., widths and thicknesses.

PMID- 20676182
TI  - Iteratively-reweighted local model fitting method for adaptive and accurate
      single-shot surface profiling.
AB  - The local model fitting (LMF) method is one of the useful single-shot surface
      profiling algorithms. The measurement principle of the LMF method relies on the
      assumption that the target surface is locally flat. Based on this assumption, the
      height of the surface at each pixel is estimated from pixel values in its
      vicinity. Therefore, we can estimate flat areas of the target surface precisely,
      whereas the measurement accuracy could be degraded in areas where the assumption
      is violated, because of a curved surface or sharp steps. In this paper, we
      propose to overcome this problem by weighting the contribution of the pixels
      according to the degree of satisfaction of the locally flat assumption. However,
      since we have no information on the surface profile beforehand, we iteratively
      estimate it and use this estimation result to determine the weights. This
      algorithm is named the iteratively-reweighted LMF (IRLMF) method. Experimental
      results show that the proposed algorithm works excellently.

PMID- 20676183
TI  - Fast-axis orientation dependence on driving voltage for a Stokes polarimeter
      based on concrete liquid-crystal variable retarders.
AB  - Nowadays liquid-crystal variable retarders (LCVRs) are widely used in optical
      systems because of their capacity to provide a controlled variable optical
      retardance by means of an applied voltage, without the need of any moving
      mechanical part. Nevertheless, the main disadvantages of these components,
      reported by users in several papers, are the necessity of using a temperature
      control system for precise measurements, the degradation under UV irradiation,
      and the lack of spatial retardance homogeneity. In this paper, we report that the
      orientation of the LCVR fast axis may also be dependent on applied voltage. The
      consideration of this phenomenon improves the performances of an imaging
      polarimeter. In this work, we present the problem, introduce the method of
      calibration that was used for the experiment, and discuss the results.

PMID- 20676184
TI  - Intensity invariant nonlinear correlation filtering in spatially disjoint noise.
AB  - We analyze the performance of a nonlinear correlation called the Locally Adaptive
      Contrast Invariant Filter in the presence of spatially disjoint noise under the
      peak-to-sidelobe ratio (PSR) metric. We show that the PSR using the nonlinear
      correlation improves as the disjoint noise intensity increases, whereas, for
      common linear filtering, it goes to zero. Experimental results as well as
      comparisons with a classical matched filter are given.

PMID- 20676185
TI  - Geometrical characteristics and damage morphology of nodules grown from
      artificial seeds in multilayer coating.
AB  - Nodules have been planted in an HfO(2)/SiO(2) multilayer system with absorptive
      gold nanoparticle seeds located on the surface of a substrate. The topography of
      nodules was scanned by an atomic force microscope and imaged by a scanning
      electron microscope. The underlying characteristics of nodules were revealed by a
      focused ion beam. The cross-sectional profiles reveal that nodules grown from
      small seeds have a continuous boundary and better mechanical stability. A laser
      induced damage test shows that nodules decrease the laser-induced damage
      threshold by up to 3 times. The damage pits are exclusively caused by nodular
      ejection and triggered by the absorptive seeds. The distribution of electric
      field and average temperature rise in the nodules were analyzed. Theoretical
      results met experimental results very well. The strong absorptive seed and
      microlens effect of the nodule play important roles in laser-induced damage of a
      planted nodule.

PMID- 20676186
TI  - Ultrastable assembly and integration technology for ground- and space-based
      optical systems.
AB  - Optical metrology systems crucially rely on the dimensional stability of the
      optical path between their individual optical components. We present in this
      paper a novel adhesive bonding technology for setup of quasi-monolithic systems
      and compare selected characteristics to the well-established state-of-the-art
      technique of hydroxide-catalysis bonding. It is demonstrated that within the
      measurement resolution of our ultraprecise custom heterodyne interferometer, both
      techniques achieve an equivalent passive path length and tilt stability for time
      scales between 0.1 mHz and 1 Hz. Furthermore, the robustness of the adhesive
      bonds against mechanical and thermal inputs has been tested, making this new
      bonding technique in particular a potential option for interferometric
      applications in future space missions. The integration process itself is eased by
      long time scales for alignment, as well as short curing times.

PMID- 20676187
TI  - Color plasmons and trains of plasmons.
AB  - We show that a broadband surface plasmon can be excited in a thin metal film. A
      train of two plasmons can be excited at conditions near the condition of
      broadband surface plasmon excitation. Also, a method for independent multichannel
      checks of biochips by wavelength addressing is proposed.

PMID- 20676188
TI  - Sensitivity of spatially resolved reflectance signals to coincident variations in
      tissue optical properties.
AB  - Canonical correlation analysis, a multivariate statistical technique, was used to
      investigate the degree of association between tissue optical properties and
      spatially resolved reflectance signals. Monte Carlo modeling was employed to
      simulate signals corresponding to different combinations of optical properties
      and these data sets were fed as input to statistical analysis. The results show
      that it is possible to adjust the separation and angular orientation of source
      and detector fibers such that the effect of a particular optical property will be
      augmented among coincident variations in other properties. The trends observed
      exhibit differences when compared with a conventional univariate sensitivity
      analysis in which only a single property is varied whereas all other parameters
      of interest are kept constant.

PMID- 20676189
TI  - Atomic layer deposited titanium dioxide and its application in resonant waveguide
      grating.
AB  - We demonstrate good optical quality TiO(2) thin films grown by atomic layer
      deposition at 120 degrees C. The optical properties were studied using
      spectroscopic ellipsometry and prism coupling methods. The refractive index was
      2.27, and the slab waveguide propagation loss was less than 1dB/cm at 1.53microm.
      A high quality resonant waveguide grating was fabricated using a thin TiO(2)
      layer on top of a SiO(2) grating.

PMID- 20676190
TI  - Single-step replication of a highly integrated PDMS optofluidic analysis system.
AB  - Micromilling is a promising technology for the fabrication of surface profiles
      with optical quality. We present a highly integrated optofluidic system made of
      polydimethylsiloxane (PDMS). The system is replicated in a single-step process
      from a micromilled polymethyl methacrylate master mold. It already includes the
      reservoirs, the channel system, as well as the optical interconnect surfaces for
      high numerical aperture objectives. We demonstrate the potential of this approach
      by laser-based three-dimensional optical manipulation within the replicated
      system. To our knowledge, this is the first time that a PDMS membrane is used as
      a well-defined channel wall for an optical trapping setup.

PMID- 20676191
TI  - Pegylated Interferon and Ribavirin Dosing Strategies to Enhance Sustained
      Virologic Response.
AB  - Hepatitis C virus (HCV) affects about 170 million people worldwide and is the
      most common chronic blood borne infection in the United States. Since the advent
      of blood screening protocols in the early 1990s, injection drug use has become
      the leading cause of infection. Hepatitis C can have both hepatic and nonhepatic
      manifestations of infection. Hepatic manifestations include hepatic fibrosis,
      cirrhosis, liver cancer, and liver failure. The standard treatment for chronic
      HCV is combination therapy with pegylated interferon-alpha and ribavirin.
      Although pegylated interferon and ribavirin has been used against HCV for close
      to a decade, advances in therapy have centered on doses and treatment durations.
      There has been increasing interest in applying on-treatment response or viral
      kinetics to predict antiviral response rates and shape therapeutic intervention.
      Protease inhibitors are a promising adjuvant to combination therapy, but their
      efficacy and safety are still under investigation.

PMID- 20676192
TI  - Clinical Trial Report: The Presence and Rupture of Vulnerable Plaques in the
      Peripheral Circulation.

PMID- 20676193
TI  - Multilayers of InGaAs Nanostructures Grown on GaAs(210) Substrates.
AB  - Multilayers of InGaAs nanostructures are grown on GaAs(210) by molecular beam
      epitaxy. With reducing the thickness of GaAs interlayer spacer, a transition from
      InGaAs quantum dashes to arrow-like nanostructures is observed by atomic force
      microscopy. Photoluminescence measurements reveal all the samples of different
      spacers with good optical properties. By adjusting the InGaAs coverage, both one
      dimensional and two-dimensional lateral ordering of InGaAs/GaAs(210)
      nanostructures are achieved.

PMID- 20676194
TI  - A kind of nanofluid consisting of surface-functionalized nanoparticles.
AB  - A method of surface functionalization of silica nanoparticles was used to
      prepare a kind of stable nanofluid. The functionalization was achieved by
      grafting silanes directly to the surface of silica nanoparticles in silica
      solutions (both a commercial solution and a self-made silica solution were used).
      The functionalized nanoparticles were used to make nanofluids, in which well
      dispersed nanoparticles can keep good stability. One of the unique
      characteristics of the nanofluids is that no deposition layer forms on the heated
      surface after a pool boiling process. The nanofluids have applicable prospect in
      thermal engineering fields with the phase-change heat transfer.

PMID- 20676195
TI  - Promoting effect of layered titanium phosphate on the electrochemical and
      photovoltaic performance of dye-sensitized solar cells.
AB  - We reported a composite electrolyte prepared by incorporating layered alpha
      titanium phosphate (alpha-TiP) into an iodide-based electrolyte using 1-ethyl-3
      methylimidazolium tetrafluoroborate(EmimBF4) ionic liquid as solvent. The
      obtained composite electrolyte exhibited excellent electrochemical and
      photovoltaic properties compared to pure ionic liquid electrolyte. Both the
      diffusion coefficient of triiodide (I3-) in the electrolyte and the charge
      transfer reaction at the electrode/electrolyte interface were improved markedly.
      The mechanism for the enhanced electrochemical properties of the composite
      electrolyte was discussed. The highest conversion efficiency of dye-sensitized
      solar cell (DSSC) was obtained for the composite electrolyte containing 1wt%
      alpha-TiP, with an improvement of 58% in the conversion efficiency than the blank
      one, which offered a broad prospect for the fabrication of stable DSSCs with a
      high conversion efficiency.

PMID- 20676196
TI  - ZnO Nanowires Synthesized by Vapor Phase Transport Deposition on Transparent
      Oxide Substrates.
AB  - Zinc oxide nanowires have been synthesized without using metal catalyst seed
      layers on fluorine-doped tin oxide (FTO) substrates by a modified vapor phase
      transport deposition process using a double-tube reactor. The unique reactor
      configuration creates a Zn-rich vapor environment that facilitates formation and
      growth of zinc oxide nanoparticles and wires (20-80 nm in diameter, up to 6 MUm
      in length, density <40 nm apart) at substrate temperatures down to 300 degrees C.
      Electron microscopy and other characterization techniques show nanowires with
      distinct morphologies when grown under different conditions. The effect of
      reaction parameters including reaction time, temperature, and carrier gas flow
      rate on the size, morphology, crystalline structure, and density of ZnO nanowires
      has been investigated. The nanowires grown by this method have a diameter,
      length, and density appropriate for use in fabricating hybrid polymer/metal oxide
      nanostructure solar cells. For example, it is preferable to have nanowires no
      more than 40 nm apart to minimize exciton recombination in polymer solar cells.

PMID- 20676197
TI  - On the morphology, structure and field emission properties of silver
      tetracyanoquinodimethane nanostructures.
AB  - Silver-tetracyanoquinodimethane(Ag-TCNQ) nanostructured arrays with different
      morphologies were grown by an organic vapor-transport reaction under different
      conditions. The field emission properties of nanostructured arrays were studied
      systematically. Their morphology and crystal structure were characterized by SEM
      and XRD, respectively. It was found that the field emission properties were
      strongly dependent on the reaction temperature and the initial Ag film thickness.
      The lowest turn-on field with 10-nm-thick silver film is about 2.0 V/MUm,
      comparable to that of carbon nanotubes. The film crystal structure and the
      morphology are contributed to the final emission performance.

PMID- 20676198
TI  - Yield Strength of Transparent MgAl2O4 Nano-Ceramic at High Pressure and
      Temperature.
AB  - We report here experimental results of yield strength and stress relaxation
      measurements of transparent MgAl2O4 nano-ceramics at high pressure and
      temperature. During compression at ambient temperature, the differential strain
      deduced from peak broadening increased significantly with pressure up to 2 GPa,
      with no clear indication of strain saturation. However, by then, warming the
      sample above 400 degrees C under 4 GPa, stress relaxation was obviously observed,
      and all subsequent plastic deformation cycles are characterized again by peak
      broadening. Our results reveal a remarkable reduction in yield strength as the
      sintering temperature increases from 400 to 900 degrees C. The low temperature
      for the onset of stress relaxation has attracted attention regarding the
      performance of transparent MgAl2O4 nano-ceramics as an engineering material.

PMID- 20676199
TI  - Fabrication of porous anodic alumina with ultrasmall nanopores.
AB  - Anodization of Al foil under low voltages of 1-10 V was conducted to obtain
      porous anodic aluminas (PAAs) with ultrasmall nanopores. Regular nanopore arrays
      with pore diameter 6-10 nm were realized in four different electrolytes under 0
      30 degrees C according to the AFM, FESEM, TEM images and current evolution
      curves. It is found that the pore diameter and interpore distance, as well as the
      barrier layer thickness, are not sensitive to the applied potentials and
      electrolytes, which is totally different from the rules of general PAA
      fabrication. The brand-new formation mechanism has been revealed by the AFM study
      on the samples anodized for very short durations of 2-60 s. It is discovered for
      the first time that the regular nanoparticles come into being under 1-10 V at the
      beginning of the anodization and then serve as a template layer dominating the
      formation of ultrasmall nanopores. Under higher potentials from 10 to 40 V, the
      surface nanoparticles will be less and less and nanopores transform into general
      PAAs.

PMID- 20676200
TI  - A Silicon Nanocrystal Schottky Junction Solar Cell produced from Colloidal
      Silicon Nanocrystals.
AB  - Solution-processed semiconductors are seen as a promising route to reducing the
      cost of the photovoltaic device manufacture. We are reporting a single-layer
      Schottky photovoltaic device that was fabricated by spin-coating intrinsic
      silicon nanocrystals (Si NCs) from colloidal suspension. The thin-film formation
      process was based on Si NCs without any ligand attachment, exchange, or removal
      reactions. The Schottky junction device showed a photovoltaic response with a
      power conversion efficiency of 0.02%, a fill factor of 0.26, short circuit
      current density of 0.148 mA/cm2, and open-circuit voltage of 0.51 V.

PMID- 20676201
TI  - A scheme for solving the plane-plane challenge in force measurements at the
      nanoscale.
AB  - Non-contact interaction between two parallel flat surfaces is a central paradigm
      in sciences. This situation is the starting point for a wealth of different
      models: the capacitor description in electrostatics, hydrodynamic flow, thermal
      exchange, the Casimir force, direct contact study, third body confinement such as
      liquids or films of soft condensed matter. The control of parallelism is so
      demanding that no versatile single force machine in this geometry has been
      proposed so far. Using a combination of nanopositioning based on inertial motors,
      of microcrystal shaping with a focused-ion beam (FIB) and of accurate in situ and
      real-time control of surface parallelism with X-ray diffraction, we propose here
      a "gedanken" surface-force machine that should enable one to measure interactions
      between movable surfaces separated by gaps in the micrometer and nanometer
      ranges.

PMID- 20676202
TI  - Synthesis and Characterization of Crystalline Silicon Carbide Nanoribbons.
AB  - In this paper, a simple method to synthesize silicon carbide (SiC) nanoribbons is
      presented. Silicon powder and carbon black powder placed in a horizontal tube
      furnace were exposed to temperatures ranging from 1,250 to 1,500 degrees C for 5
      12 h in an argon atmosphere at atmospheric pressure. The resulting SiC
      nanoribbons were tens to hundreds of microns in length, a few microns in width
      and tens of nanometers in thickness. The nanoribbons were characterized with
      electron microscopy, energy-dispersive X-ray spectroscopy, X-ray diffraction,
      Raman spectroscopy and X-ray photoelectron spectroscopy, and were found to be
      hexagonal wurtzite-type SiC (2H-SiC) with a growth direction of [1010]. The
      influence of the synthesis conditions such as the reaction temperature, reaction
      duration and chamber pressure on the growth of the SiC nanomaterial was
      investigated. A vapor-solid reaction dominated nanoribbon growth mechanism was
      discussed.

PMID- 20676203
TI  - Magnetic Properties of Ni-doped ZnO Nanocombs by CVD Approach.
AB  - The search for above room temperature ferromagnetism in dilute magnetic
      semiconductors has been intense in recent year. Arrays of perpendicular
      ferromagnetic nanowire/rods have recently attracted considerable interest for
      their potential use in many areas of advanced nanotechnology. We report a simple
      low-temperature chemical vapor deposition (CVD) to create self-assembled comb
      like Ni-/undoped ZnO nanostructure arrays. The phases, compositions, and physical
      properties of the studied samples were analyzed by different techniques,
      including high-resolution X-ray diffraction/photoelectron
      spectroscopy/transmission electron microscopy, photoluminescence, and MPMS. In
      particular, the Ni-doped ZnO nanocombs (NCs) with ferromagnetic and
      superparamagnetic properties have been observed whereas undoped ZnO NCs
      disappear. The corresponding ferromagnetic source mechanism is discussed, in
      which defects such as O vacancies would play an important role.

PMID- 20676204
TI  - Formation of PbSe/CdSe Core/Shell Nanocrystals for Stable Near-Infrared High
      Photoluminescence Emission.
AB  - PbSe/CdSe core/shell nanocrystals with quantum yield of 70% were obtained by the
      "successive ion layer adsorption and reaction" technology in solution. The
      thickness of the CdSe shell was exactly controlled. A series of spectral red
      shifts with the CdSe shell growth were observed, which was attributed to the
      combined effect of the surface polarization and the expansion of carriers'
      wavefunctions. The stability of PbSe nanocrystals was tremendously improved with
      CdSe shells.

PMID- 20676205
TI  - Superlattice Growth via MBE and Green's Function Techniques.
AB  - A model has been developed to simulate the growth of arrays consisting of a
      substrate on which alternating layers of quantum dots (QDs) and spacer layers are
      epitaxially grown. The substrate and spacer layers are modeled as an anisotropic
      elastic half-space, and the QDs are modeled as point inclusions buried within the
      half-space. In this model, the strain at the free surface of this half-space due
      to the buried point QDs is calculated, and a scalar measure of the strain at the
      surface is subsequently determined. New point QDs are placed on the surface where
      the previously calculated scalar strain measure is a minimum. Following available
      DFT results, this scalar strain measure is a weighted average of the in-plane
      strains. This model is constructed under the assumption that diffusional
      anisotropy can be neglected, and thus, the results are more in agreement with
      results from experiments of growth of SiGe QDs than experiments involving QDs of
      (In,Ga)As.

PMID- 20676206
TI  - Measurement of w-InN/h-BN Heterojunction Band Offsets by X-Ray Photoemission
      Spectroscopy.
AB  - X-ray photoelectron spectroscopy has been used to measure the valence band
      offset (VBO) of the w-InN/h-BN heterojunction. We find that it is a type-II
      heterojunction with the VBO being -0.30 +/- 0.09 eV and the corresponding
      conduction band offset (CBO) being 4.99 +/- 0.09 eV. The accurate determination
      of VBO and CBO is important for designing the w-InN/h-BN-based electronic
      devices.

PMID- 20676207
TI  - Biosynthesis of gold nanoparticles by foliar broths: roles of biocompounds and
      other attributes of the extracts.
AB  - Biosynthesis of nanoparticles has arisen as a promising alternative to
      conventional synthetic methodologies owing to its eco-friendly advantages, and
      the involved bioprotocol still needs further clarification. This research, for
      the first time from the standpoint of statistics, confirmed an electrostatic
      force or ionic bond-based interaction between the chloroauric ions and the
      involved bioconstituents and manifested that reducing sugars and flavonoids were
      both important reductants responsible for conversion of Au(III) to Au(0). The
      result also demonstrated that the proteins were not the reducing agents, yet they
      might be protection agents in biosynthesis of gold nanoparticles (GNPs). Besides,
      a significant linear relationship was found between the anti-oxidant ability of
      the foliar broths and their capability to reduce Au(III) into Au(0). Furthermore,
      the preliminary investigation based on the boxplot on the size/shape distribution
      of the biosynthesized GNPs revealed that gold nanospheres with higher degree of
      homogeneity in size tended to be promoted by foliar broths containing higher
      content of reducing sugars/flavonoids and proteins. Otherwise, i.e., for those
      broths with lower content of the above biocompounds, sphere GNPs of wider size
      distribution or even gold nanotriangles tended to be fabricated.(See
      supplementary material 1).

PMID- 20676208
TI  - Glassy state lead tellurite nanobelts: synthesis and properties.
AB  - The lead tellurite nanobelts have been first synthesized in the composite molten
      salts (KNO3/LiNO3) method, which is cost-effective, one-step, easy to control,
      and performed at low-temperature and in ambient atmosphere. Scanning electron
      microscopy, X-ray diffraction, transmission electron microscopy, X-ray
      photoelectron spectrum, energy dispersive X-ray spectroscopy and FT-IR spectrum
      are used to characterize the structure, morphology, and composition of the
      samples. The results show that the as-synthesized products are amorphous and
      glassy nanobelts with widths of 200-300 nm and lengths up to tens of microns and
      the atomic ratio of Pb:Te:O is close to 1:1.5:4. Thermo-gravimetric analysis
      (TGA) and differential scanning calorimetry (DSC) and investigations of the
      corresponding structure and morphology change confirm that the nanobelts have low
      glass transition temperature and thermal stability. Optical diffuse reflectance
      spectrum indicates that the lead tellurite nanobelts have two optical gaps at ca.
      3.72 eV and 4.12 eV. Photoluminescence (PL) spectrum and fluorescence imaging of
      the products exhibit a blue emission (round 480 nm).

PMID- 20676209
TI  - Synthesis and Characterization of Cobalt-Doped WS2 Nanorods for Lithium Battery
      Applications.
AB  - Cobalt-doped tungsten disulfide nanorods were synthesized by an approach
      involving exfoliation, intercalation, and the hydrothermal process, using
      commercial WS2 powder as the precursor and n-butyllithium as the exfoliating
      reagent. XRD results indicate that the crystal phase of the sample is 2H-WS2. TEM
      images show that the sample consists of bamboo-like nanorods with a diameter of
      around 20 nm and a length of about 200 nm. The Co-doped WS2 nanorods exhibit the
      reversible capacity of 568 mAh g-1 in a voltage range of 0.01-3.0 V versus
      Li/Li+. As an electrode material for the lithium battery, the Co-doped WS2
      nanorods show enhanced charge capacity and cycling stability compared with the
      raw WS2 powder.

PMID- 20676210
TI  - Selective Synthesis of Fe2O3 and Fe3O4 Nanowires Via a Single Precursor: A
      General Method for Metal Oxide Nanowires.
AB  - Hematite (alpha-Fe2O3) and magnetite (Fe3O4) nanowires with the diameter of
      about 100 nm and the length of tens of micrometers have been selectively
      synthesized by a microemulsion-based method in combination of the calcinations
      under different atmosphere. The effects of the precursors, annealing temperature,
      and atmosphere on the morphology and the structure of the products have been
      investigated. Moreover, Co3O4 nanowires have been fabricated to confirm the
      versatility of the method for metal oxide nanowires.

PMID- 20676211
TI  - Synthesis, magnetic anisotropy and optical properties of preferred oriented zinc
      ferrite nanowire arrays.
AB  - Preferred oriented ZnFe2O4 nanowire arrays with an average diameter of 16 nm
      were fabricated by post-annealing of ZnFe2 nanowires within anodic aluminum oxide
      templates in atmosphere. Selected area electron diffraction and X-ray diffraction
      exhibit that the nanowires are in cubic spinel-type structure with a [110]
      preferred crystallite orientation. Magnetic measurement indicates that the as
      prepared ZnFe2O4 nanowire arrays reveal uniaxial magnetic anisotropy, and the
      easy magnetization direction is parallel to the axis of nanowire. The optical
      properties show the ZnFe2O4 nanowire arrays give out 370-520 nm blue-violet
      light, and their UV absorption edge is around 700 nm. The estimated values of
      direct and indirect band gaps for the nanowires are 2.23 and 1.73 eV,
      respectively.

PMID- 20676212
TI  - Anti-cyanobacterial activity of Moringa oleifera seeds.
AB  - Filtrates from crushed Moringa oleifera seeds were tested for their effects on
      growth and Photosystem II efficiency of the common bloom-forming cyanobacterium
      Microcystis aeruginosa. M. aeruginosa populations exhibited good growth in
      controls and treatments with 4- and 8-mg crushed Moringa seeds per liter, having
      similar growth rates of 0.50 (+/-0.01) per day. In exposures of 20- to 160-mg
      crushed Moringa seeds L(-1), growth rates were negative and on average -0.23 (+/
      0.05) .day(-1). Presumably, in the higher doses of 20- to 160-mg crushed seeds
      per liter, the cyanobacteria died, which was supported by a rapid drop in the
      Photosystem II efficiency (Phi(PSII)), while the Phi(PSII) was high and
      unaffected in 0, 4, and 8 mg L(-1). High-density populations of M. aeruginosa
      (chlorophyll-a concentrations of approximately 270 microg L(-1)) were reduced to
      very low levels within 2 weeks of exposure to >/=80-mg crushed seeds per liter.
      At the highest dosage of 160 mg L(-1), the Phi(PSII) dropped to zero rapidly and
      remained nil during the course of the experiment (14 days). Hence, under
      laboratory conditions, a complete wipeout of the bloom could be achieved. This is
      the first study that yielded evidence for cyanobactericidal activity of filtrate
      from crushed Moringa seeds, suggesting that Moringa seed extracts might have a
      potential as an effect-oriented measure lessening cyanobacterial nuisance.

PMID- 20676213
TI  - Virology Experts in the Boundary Zone Between Science, Policy and the Public: A
      Biographical Analysis.
AB  - This article aims to open up the biographical black box of three experts working
      in the boundary zone between science, policy and public debate. A biographical
      narrative approach is used to analyse the roles played by the virologists Albert
      Osterhaus, Roel Coutinho and Jaap Goudsmit in policy and public debate. These
      figures were among the few leading virologists visibly active in the Netherlands
      during the revival of infectious diseases in the 1980s. Osterhaus and Coutinho in
      particular are still the key figures today, as demonstrated during the outbreak
      of novel influenza A (H1N1). This article studies the various political and
      communicative challenges and dilemmas encountered by these three virologists, and
      discusses the way in which, strategically or not, they handled those challenges
      and dilemmas during the various stages of the field's recent history. Important
      in this respect is their pursuit of a public role that is both effective and
      credible. We will conclude with a reflection on the H1N1 pandemic, and the
      historical and biographical ties between emerging governance arrangements and the
      experts involved in the development of such arrangements.

PMID- 20676214
TI  - Nanofluids research: key issues.
AB  - Nanofluids are a new class of fluids engineered by dispersing nanometer-size
      structures (particles, fibers, tubes, droplets) in base fluids. The very essence
      of nanofluids research and development is to enhance fluid macroscopic and
      megascale properties such as thermal conductivity through manipulating
      microscopic physics (structures, properties and activities). Therefore, the
      success of nanofluid technology depends very much on how well we can address
      issues like effective means of microscale manipulation, interplays among physics
      at different scales and optimization of microscale physics for the optimal
      megascale properties. In this work, we take heat-conduction nanofluids as
      examples to review methodologies available to effectively tackle these key but
      difficult problems and identify the future research needs as well. The reviewed
      techniques include nanofluids synthesis through liquid-phase chemical reactions
      in continuous-flow microfluidic microreactors, scaling-up by the volume averaging
      and constructal design with the constructal theory. The identified areas of
      future research contain microfluidic nanofluids, thermal waves and constructal
      nanofluids.

PMID- 20676215
TI  - Dimensions of Negative Thinking and the Relations with Symptoms of Depression and
      Anxiety in Children and Adolescents.
AB  - The current study sought to examine three forms of negative, repetitive thinking
      in non-clinical children and adolescents aged between 10 and 18. More
      specifically, this study addressed the degree to which stress-reactive rumination
      can be differentiated from other forms of repetitive thinking, such as emotion
      focused rumination and worry, and the associations between the various indices of
      repetitive thinking and symptoms of anxiety and depression. Participants
      completed a battery of self-report questionnaires including measures of stress
      reactive rumination, emotion-focused rumination, worry, and symptoms of anxiety
      and depression. Results showed that stress-reactive rumination, emotion-focused
      rumination and worry are related but distinct forms of repetitive negative
      thinking. Positive associations were found between all indices of repetitive
      thinking and symptoms of depression and anxiety, but the effects of emotion
      focused rumination disappeared when controlling for the other forms of repetitive
      thinking. The findings are discussed in the light of current theories and
      previous research, and directions for future research are provided.

PMID- 20676216
TI  - "Lossless" compression of high resolution mass spectra of small molecules.
AB  - Fourier transform ion cyclotron resonance (FTICR) provides the highest resolving
      power of any commercially available mass spectrometer. This advantage is most
      significant for species of low mass-to-charge ratio (m/z), such as metabolites.
      Unfortunately, FTICR spectra contain a very large number of data points, most of
      which are noise. This is most pronounced at the low m/z end of spectra, where
      data point density is the highest but peak density low. We therefore developed a
      filter that offers lossless compression of FTICR mass spectra from singly charged
      metabolites. The filter relies on the high resolving power and mass measurement
      precision of FTICR and removes only those m/z channels that cannot contain signal
      from singly charged organic species. The resulting pseudospectra still contain
      the same signal as the original spectra but less uninformative background. The
      filter does not affect the outcome of standard downstream chemometric analysis
      methods, such as principal component analysis, but use of the filter
      significantly reduces memory requirements and CPU time for such analyses. We
      demonstrate the utility of the filter for urinary metabolite profiling using
      direct infusion electrospray ionization and a 15 tesla FTICR mass spectrometer.
      ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article
      (doi:10.1007/s11306-010-0202-2) contains supplementary material, which is
      available to authorized users.

PMID- 20676217
TI  - Metabolic assessment of a novel chronic myelogenous leukemic cell line and an
      imatinib resistant subline by H NMR spectroscopy.
AB  - The goal of this study was to examine metabolic differences between a novel
      chronic myelogenous leukemic (CML) cell line, MyL, and a sub-clone, MyL-R, which
      displays enhanced resistance to the targeted Bcr-Abl tyrosine kinase inhibitor
      imatinib. (1)H nuclear magnetic resonance (NMR) spectroscopy was carried out on
      cell extracts and conditioned media from each cell type. Both principal component
      analysis (PCA) and specific metabolite identification and quantification were
      used to examine metabolic differences between the cell types. MyL cells showed
      enhanced glucose removal from the media compared to MyL-R cells with significant
      differences in production rates of the glycolytic end-products, lactate and
      alanine. Interestingly, the total intracellular creatine pool (creatine +
      phosphocreatine) was significantly elevated in MyL-R compared to MyL cells. We
      further demonstrated that the MyL-R cells converted the creatine to
      phosphocreatine using non-invasive monitoring of perfused alginate-encapsulated
      MyL-R and MyL cells by in vivo (31)P NMR spectroscopy and subsequent HPLC
      analysis of extracts. Our data demonstrated a clear difference in the metabolite
      profiles of drug-resistant and sensitive cells, with the biggest difference being
      an elevation of creatine metabolites in the imatinib-resistant MyL-R cells.

PMID- 20676218
TI  - Metabonomic fingerprints of fasting plasma and spot urine reveal human pre
      diabetic metabolic traits.
AB  - Impaired glucose tolerance (IGT) which precedes overt type 2 diabetes (T2DM) for
      decades is associated with multiple metabolic alterations in insulin sensitive
      tissues. In an UPLC-qTOF-mass spectrometry-driven non-targeted metabonomics
      approach we investigated plasma as well as spot urine of 51 non-diabetic,
      overnight fasted individuals aiming to separate subjects with IGT from controls
      thereby identify pathways affected by the pre-diabetic metabolic state. We could
      clearly demonstrate that normal glucose tolerant (NGT) and IGT subjects clustered
      in two distinct groups independent of the investigated metabonome. These findings
      reflect considerable differences in individual metabolite fingerprints, both in
      plasma and urine. Pre-diabetes associated alterations in fatty acid-, tryptophan
      , uric acid-, bile acid-, and lysophosphatidylcholine-metabolism, as well as the
      TCA cycle were identified. Of note, individuals with IGT also showed decreased
      levels of gut flora-associated metabolites namely hippuric acid, methylxanthine,
      methyluric acid, and 3-hydroxyhippuric acid. The findings of our non-targeted
      UPLC-qTOF-MS metabonomics analysis in plasma and spot urine of individuals with
      IGT vs NGT offers novel insights into the metabolic alterations occurring in the
      long, asymptomatic period preceding the manifestation of T2DM thereby giving
      prospects for new intervention targets. ELECTRONIC SUPPLEMENTARY MATERIAL: The
      online version of this article (doi:10.1007/s11306-010-0203-1) contains
      supplementary material, which is available to authorized users.

PMID- 20676219
TI  - Alcohol dependence in women: Comorbidities can complicate treatment.

PMID- 20676220
TI  - An evolutionarily conserved arginine is essential for Tre1 G protein-coupled
      receptor function during germ cell migration in Drosophila melanogaster.
AB  - BACKGROUND: G protein-coupled receptors (GPCRs) play central roles in mediating
      cellular responses to environmental signals leading to changes in cell physiology
      and behaviors, including cell migration. Numerous clinical pathologies including
      metastasis, an invasive form of cell migration, have been linked to abnormal GPCR
      signaling. While the structures of some GPCRs have been defined, the in vivo
      roles of conserved amino acid residues and their relationships to receptor
      function are not fully understood. Trapped in endoderm 1 (Tre1) is an orphan
      receptor of the rhodopsin class that is necessary for primordial germ cell
      migration in Drosophila melanogaster embryos. In this study, we employ molecular
      genetic approaches to identify residues in Tre1 that are critical to its
      functions in germ cell migration. METHODOLOGY/PRINCIPAL FINDINGS: First, we show
      that the previously reported scattershot mutation is an allele of tre1. The
      scattershot allele results in an in-frame deletion of 8 amino acids at the
      junction of the third transmembrane domain and the second intracellular loop of
      Tre1 that dramatically impairs the function of this GPCR in germ cell migration.
      To further refine the molecular basis for this phenotype, we assayed the effects
      of single amino acid substitutions in transgenic animals and determined that the
      arginine within the evolutionarily conserved E/N/DRY motif is critical for
      receptor function in mediating germ cell migration within an intact developing
      embryo. CONCLUSIONS/SIGNIFICANCE: These structure-function studies of GPCR
      signaling in native contexts will inform future studies into the basic biology of
      this large and clinically important family of receptors.

PMID- 20676221
TI  - Leukocyte Count versus C-Reactive Protein Levels in Obese Portuguese Patients
      Aged 6-12 Years Old.
AB  - OBJECTIVES: to evaluate whether total and differential WBC counts are altered in
      young obese patients (aged 6-12 years) and if a relationship exists between WBC
      counts and the severity of obesity as well as with CRP level. MATERIALS AND
      METHODS: a group of 77 obese patients [32 males and 45 females] and 19 controls
      [7 males and 12 females] were studied. Total WBC count was performed by using an
      automatic blood cell counter. Blood cell morphology and WBC differential count
      were evaluated in Wright stained blood films. The plasma levels of CRP were
      evaluated by immunoturbidimetry. RESULTS: obese participants presented with a
      statistically significant higher neutrophil percentage and CRP levels when
      compared to controls; the median CRP value was about 5 times higher than that
      observed in controls. Absolute neutrophil count and neutrophil/lymphocyte ratio
      were also higher in patients, though without statistical significance. The
      parameters that were statistically significant related with adiposity markers
      were neutrophil count and CRP levels. The neutrophil count was positively and
      statistically correlated with body mass index (BMI), BMI z-score, waist
      circumference and waist/height ratio, and also with CRP levels. In multiple
      regression analysis, the only variable that remained statistically associated
      with neutrophil count was CRP (neutrophil count = 2.612 + 0.439lnCRP;
      standardised coefficient/beta: 0.384, P=0.001). When performing multiple
      regression without CRP, the only variable that remained statistically associated
      with neutrophil count was BMI. CONCLUSIONS: our results demonstrated in obese
      patients aged 6-12 years, a significant change in the differential leukocyte
      count towards neutrophilia, together with a significant higher CRP concentration,
      and that absolute neutrophil count correlates with obesity markers and with CRP
      levels. Our data also indicate that neutrophil count, a current clinically used
      low-cost parameter, may be used as an obesity-related inflammatory marker in
      young obese patients.

PMID- 20676222
TI  - Potential therapeutic effects of vitamin e and C on placental oxidative stress
      induced by nicotine: an in vitro evidence.
AB  - There have been a few studies that examined the oxidative stress effects of
      nicotine during pregnancy and lactation. The adverse effect of prenatal smoking
      exposure on human fetal development and growth has been a major public health
      issue. Active or passive smoking during pregnancy can result in a wide variety of
      adverse outcomes, including intrauterine growth retardation (IUGR), prematurity,
      stillbirth, and the sudden infant death syndrome. Smoking in pregnancy has also
      been associated with an increased risk of attention deficit and learning problems
      in childhood. Some studies argued that as a principal component of tobacco smoke,
      nicotine alone is responsible for the majority of negative reproductive outcomes.
      Nicotine and its major metabolite cotinine can cross the placental barrier. The
      level of nicotine in fetal tissues was found to be equal to or greater than the
      plasma nicotine level in the mothers. The oxidative stress induce by nicotine has
      been increasingly postulated as a major contributor to endothelial dysfunction. A
      large body of research has investigated the potential role of antioxidant
      nutrients in the prevention of endothelial dysfunction in women. Therefore, the
      present study was undertaken to assess the potential benefit of antioxidant
      supplementation on markers of placental oxidative stress in an in vitro model of
      endothelial dysfunction induced by nicotine, since it was previously found that
      nicotine is able to trigger the placental secretion of stress molecules. In this
      regard, we evaluated the effects of vitamin C, vitamin E and N-acetylcysteine
      (NAC), alone or in combination, in placental villi culture after exposure to
      nicotine. The effect of antioxidant nutrients on trophoblast cells proliferation
      and vitality was also evaluated. The results obtained suggest that in a patho
      physiological condition, such as endothelial dysfunction induced by nicotine, the
      deleterious effect of reactive oxygen species may be counteracted by an
      antioxidant therapy, and there is the need to investigate the optimum dosing and
      timing of antioxidants administration, since an inappropriate antioxidant
      treatment in pregnant women may have deleterious consequences, reducing placental
      cells proliferation until to cell death.

PMID- 20676223
TI  - Design and Synthesis of Functionalized Trisaccharides as p53-Peptide Mimics.
AB  - Oligosaccharides represent potentially useful scaffolds for the development of
      peptidomimetics. We report here the design and synthesis of functionalized
      trisaccharides modeled after an alpha-helical 15-mer peptide region of p53 which
      binds to its cellular regulator MDM2. The trisaccharide scaffold was obtained
      efficiently by applying the sulfoxide glycosylation reaction as a key
      methodology.

PMID- 20676224
TI  - Development of Clinical Trial Assessments for the Study of Interstitial Lung
      Disease in Patients who have Connective Tissue Diseases-Methodological
      Considerations.
AB  - This review article discusses the proposed methodology that will be utilized to
      develop core set items for connective tissue disease-associated interstitial lung
      disease (CTD-ILD). CTD-ILD remain an important enigma in clinical medicine. No
      consensus exists on measurement of disease activity or what constitutes a
      significant response to therapeutic interventions. Lack of appropriate measures
      inhibit effective drug development and hamper regulatory evaluation of candidate
      therapies.An interdisciplinary and international Steering Committee (SC) will
      oversee the execution of a 3-tier Delphi exercise involving experts in CTD and
      ILD. In parallel to the Delphi, qualitative information will be gathered from
      patients with ILD using focus groups. These data will subsequently be used to
      construct surveys to collect quantitative response from patients with ILD. The
      final Delphi and Patient Perspective results are to be scrutinized by SC and
      specialty sub-groups (including patient advocates) for truth, discrimination and
      feasibility - the OMERACT filters. Through application of Nominal Group
      technique, a core set of outcome measures will be proposed. Subsequent exercises
      will evaluate the applicability of a proposed core set to the unique issues posed
      by individual CTDs in addition to guidelines on screening, prognostication and
      damage scoring.

PMID- 20676225
TI  - Force feature spaces for visualization and classification.
AB  - Distance-preserving dimension reduction techniques can fail to separate elements
      of different classes when the neighborhood structure does not carry sufficient
      class information. We introduce a new visual technique, K-epsilon diagrams, to
      analyze dataset topological structure and to assess whether intra-class and inter
      class neighborhoods can be distinguished.We propose a force feature space data
      transform that emphasizes similarities between same-class points and enhances
      class separability. We show that the force feature space transform combined with
      distance-preserving dimension reduction produces better visualizations than
      dimension reduction alone. When used for classification, force feature spaces
      improve performance of K-nearest neighbor classifiers. Furthermore, the quality
      of force feature space transformations can be assessed using K-epsilon diagrams.

PMID- 20676226
TI  - Improved Statistical Methods are Needed to Advance Personalized Medicine.
AB  - Common methods of statistical analysis, e.g. Analysis of Variance and
      Discriminant Analysis, are not necessarily optimal in selecting therapy for an
      individual patient. These methods rely on group differences to identify markers
      for disease or successful interventions and ignore sub-group differences when the
      number of sub-groups is large. In these circumstances, they provide the same
      advice to an individual as the average patient. Personalized medicine needs new
      statistical methods that allow treatment efficacy to be tailored to a specific
      patient, based on a large number of patient characteristics. One such approach is
      the sequential k-nearest neighbor analysis (patients-like-me algorithm). In this
      approach, the k most similar patients are examined sequentially until a
      statistically significant conclusion about the efficacy of treatment for the
      patient-at-hand can be arrived at. For some patients, the algorithm stops before
      the entire set of data is examined and provides beneficial advice that may
      contradict recommendations made to the average patient. Many problems remain in
      creating statistical tools that can help individual patients but this is an
      important area in which progress in statistical thinking is helpful.

PMID- 20676227
TI  - Systemic Sclerosis-Associated Interstitial Lung Disease: Lessons from Clinical
      Trials, Outcome Measures, and Future Study Design.
AB  - Pulmonary involvement including interstitial lung disease (ILD) is the leading
      cause of mortality in patients with systemic sclerosis (scleroderma; SSc). This
      article reviews the current evidence based medicine regarding available therapies
      for SSc-ILD ; discusses the lessons learned from recent SSc-ILD randomized
      controlled trials (RCTs); and proposes outcome measures and recommendations for
      design of future RCTs for SSc-ILD.

PMID- 20676229
TI  - Hierarchical Spatial Process Models for Multiple Traits in Large Genetic Trials.
AB  - This article expands upon recent interest in Bayesian hierarchical models in
      quantitative genetics by developing spatial process models for inference on
      additive and dominance genetic variance within the context of large spatially
      referenced trial datasets of multiple traits of interest. Direct application of
      such multivariate models to large spatial datasets is often computationally
      infeasible because of cubic order matrix algorithms involved in estimation. The
      situation is even worse in Markov chain Monte Carlo (MCMC) contexts where such
      computations are performed for several thousand iterations. Here, we discuss
      approaches that help obviate these hurdles without sacrificing the richness in
      modeling. For genetic effects, we demonstrate how an initial spectral
      decomposition of the relationship matrices negates the expensive matrix
      inversions required in previously proposed MCMC methods. For spatial effects we
      discuss a multivariate predictive process that reduces the computational burden
      by projecting the original process onto a subspace generated by realizations of
      the original process at a specified set of locations (or knots). We illustrate
      the proposed methods using a synthetic dataset with multivariate additive and
      dominant genetic effects and anisotropic spatial residuals, and a large dataset
      from a scots pine (Pinus sylvestris L.) progeny study conducted in northern
      Sweden. Our approaches enable us to provide a comprehensive analysis of this
      large trial which amply demonstrates that, in addition to violating basic
      assumptions of the linear model, ignoring spatial effects can result in
      downwardly biased measures of heritability.

PMID- 20676230
TI  - A Real Time Coincidence System for High Count-Rate TOF or Non-TOF PET Cameras
      Using Hybrid Method Combining AND-Logic and Time-Mark Technology.
AB  - A fully digital FPGA-based high count-rate coincidence system has been developed
      for TOF (Time of Flight) and non-TOF PET cameras. Using a hybrid of AND-logic and
      Time-mark technology produced both excellent timing resolution and high
      processing speed. In this hybrid architecture, every gamma event was synchronized
      by a 125 MHz system clock and generating a trigger associated with a time-mark
      given by an 8-bit high-resolution TDC (68.3 ps/bin). AND-logic was applied to the
      synchronized triggers for the real-time raw sorting of coincident events. An
      efficient FPGA based Time-mark fine-sort algorithm is used to select all the
      possible coincidence events within the preset coincidence time window. This FPGA
      based coincidence system for a modular PET camera offers reprogrammable
      flexibility and expandability, so the coincidence system is easily employed,
      regardless of differences in the scale of the PET camera detector setup. A
      distributed processing method and pipeline technology were adopted in the design
      to obtain very high processing speed. In this design, both prompt and time
      delayed accidental coincidences are simultaneously processed in real time. The
      real-time digital coincidence system supports coincidence in 2 to 12 detector
      module setups, capable of processing 72 million single events per second with no
      digital data loss and captures multiple-event coincidence for better imaging
      performance evaluation. The coincidence time window-size and time-offset of each
      coincidence event pair can be programmed independently in 68.3 ps increments (TDC
      LSB) during the data acquisition in different applications to optimize the signal
      to-noise ratio. The complex coincidence system is integrated in one circuit board
      with 1.5 Gbps fiber optic interface. We demonstrated the system performance using
      the actual circuit and Monte Carlo simulations.

PMID- 20676232
TI  - The genetic correlation between flower size and water use efficiency in
      monkeyflowers.
AB  - QUESTION: Does water loss during drought stress represent an important
      physiological constraint on the evolution of flower size? ORGANISM: A genetically
      diverse population of Mimulus guttatus (yellow monkeyflower) originally sampled
      from an alpine meadow in Oregon, USA. METHODS: We grew plants of three different
      genotypic classes (small, medium, and large flowered) under both well-watered and
      drought-stress conditions and measured water use efficiency using stable carbon
      isotopes. RESULTS: There was no difference in water use efficiency among flower
      size genotypes under well-watered conditions, but the water use efficiency of
      small-flowered plants was substantially lower than that of medium or large
      genotypes under drought stress. Whether this paradoxical result is a direct
      effect of flower size or an indirect (i.e. pleiotropic) effect, the presence of a
      genetic correlation between floral and physiological traits indicates that
      selection of one does impact the other.

PMID- 20676231
TI  - Specificity of the acute tryptophan and tyrosine plus phenylalanine depletion and
      loading tests I. Review of biochemical aspects and poor specificity of current
      amino Acid formulations.
AB  - The acute tryptophan or tyrosine plus phenylalanine depletion and loading tests
      are powerful tools for studying the roles of serotonin, dopamine and
      noradrenaline in normal subjects and those with behavioural disorders. The
      current amino acid formulations for these tests, however, are associated with
      undesirable decreases in ratios of tryptophan or tyrosine plus phenylalanine to
      competing amino acids resulting in loss of specificity. This could confound
      biochemical and behavioural findings. Compositions of current formulations are
      reviewed, the biochemical principles underpinning the tests are revisited and
      examples of unintended changes in the above ratios and their impact on monoamine
      function and behaviour will be demonstrated from data in the literature. The
      presence of excessive amounts of the 3 branched-chain amino acids Leu, Ile and
      Val is responsible for these unintended decreases and the consequent loss of
      specificity. Strategies for enhancing the specificity of the different
      formulations are proposed.

PMID- 20676233
TI  - Solid-State NMR Studies of Chemically Lithiated CF.
AB  - Three types of fluorinated carbon, all in their original form and upon sequential
      chemical lithiations via n-butyllithium, were investigated by (13)C and (19)F
      solid-state NMR methods. The three starting CF(x) materials [where x = 1
      (nominally)] were fiber based, graphite based, and petroleum coke based. The aim
      of the current study was to identify, at the atomic/molecular structural level,
      factors that might account for differences in electrochemical performance among
      the different kinds of CF(x). Differences were noted in the covalent F character
      among the starting compounds and in the details of LiF production among the
      lithiated samples.

PMID- 20676234
TI  - Behavioral profiles of three C57BL/6 substrains.
AB  - C57BL/6 inbred strains of mice are widely used in knockout and transgenic
      research. To evaluate the loss-of-function and gain-of-function effects of the
      gene of interest, animal behaviors are often examined. However, an issue of
      C57BL/6 substrains that is not always appreciated is that behaviors are known to
      be strongly influenced by genetic background. To investigate the behavioral
      characteristics of C57BL/6 substrains, we subjected C57BL/6J, C57BL/6N, and
      C57BL/6C mice to a behavior test battery. We performed both a regular scale
      analysis, in which experimental conditions were tightly controlled, and large
      scale analysis from large number of behavioral data that we have collected so far
      through the comprehensive behavioral test battery applied to 700-2,200 mice in
      total. Significant differences among the substrains were found in the results of
      various behavioral tests, including the open field, rotarod, elevated plus maze,
      prepulse inhibition, Porsolt forced swim, and spatial working memory version of
      the eight-arm radial maze. Our results show a divergence of behavioral
      performance in C57BL/6 substrains, which suggest that small genetic differences
      may have a great influence on behavioral phenotypes. Thus, the genetic background
      of different substrains should be carefully chosen, equated, and considered in
      the interpretation of mutant behavioral phenotypes.

PMID- 20676235
TI  - Alarm pheromone processing in the ant brain: an evolutionary perspective.
AB  - Social insects exhibit sophisticated communication by means of pheromones, one
      example of which is the use of alarm pheromones to alert nestmates for colony
      defense. We review recent advances in the understanding of the processing of
      alarm pheromone information in the ant brain. We found that information about
      formic acid and n-undecane, alarm pheromone components, is processed in a set of
      specific glomeruli in the antennal lobe of the ant Camponotus obscuripes. Alarm
      pheromone information is then transmitted, via projection neurons (PNs), to the
      lateral horn and the calyces of the mushroom body of the protocerebrum. In the
      lateral horn, we found a specific area where terminal boutons of alarm pheromone
      sensitive PNs are more densely distributed than in the rest of the lateral horn.
      Some neurons in the protocerebrum responded specifically to formic acid or n
      undecane and they may participate in the control of behavioral responses to each
      pheromone component. Other neurons, especially those originating from the
      mushroom body lobe, responded also to non-pheromonal odors and may play roles in
      integration of pheromonal and non-pheromonal signals. We found that a class of
      neurons receive inputs in the lateral horn and the mushroom body lobe and
      terminate in a variety of premotor areas. These neurons may participate in the
      control of aggressive behavior, which is sensitized by alarm pheromones and is
      triggered by non-pheromonal sensory stimuli associated with a potential enemy. We
      propose that the alarm pheromone processing system has evolved by differentiation
      of a part of general odor processing system.

PMID- 20676236
TI  - Measurement of neuronal activity in a macaque monkey in response to animate
      images using near-infrared spectroscopy.
AB  - Near-infrared spectroscopy (NIRS) has been used extensively for functional
      neuroimaging over the past decade, in part because it is considered a powerful
      tool for investigating brain function in human infants and young children, for
      whom other neuroimaging techniques are not suitable. In particular, several
      studies have measured hemodynamic responses in the occipital region in infants
      upon exposure to visual stimuli. In the present study, we used a multi-channel
      NIRS to measure neuronal activity in a macaque monkey who was trained to watch
      videos showing various circus animals performing acrobatic activities without
      fixing the head position of the monkey. Cortical activity from the occipital
      region was measured first by placing a probe comprising a 3 x 5 array of emitters
      and detectors (2 x 4 cm) on the area (area 17), and the robustness and stability
      of the results were confirmed across sessions. Cortical responses were then
      measured from the dorsofrontal region. The oxygenated hemoglobin signals
      increased in area 9 and decreased in area 8b in response to viewing the videos.
      The results suggest that these regions are involved in cognitive processing of
      visually presented stimuli. The monkey showed positive responsiveness to the
      stimuli from the affective standpoint, but its attentional response to them was
      an inhibitory one.

PMID- 20676237
TI  - Correlative microscopy of densely labeled projection neurons using neural
      tracers.
AB  - Three-dimensional morphological information about neural microcircuits is of high
      interest in neuroscience, but acquiring this information remains challenging. A
      promising new correlative technique for brain imaging is array tomography
      (Micheva and Smith, 2007), in which series of ultrathin brain sections are
      treated with fluorescent antibodies against neurotransmitters and synaptic
      proteins. Treated sections are repeatedly imaged in the fluorescence light
      microscope (FLM) and then in the electron microscope (EM). We explore a similar
      correlative imaging technique in which we differentially label distinct
      populations of projection neurons, the key routers of electrical signals in the
      brain. In songbirds, projection neurons can easily be labeled using neural
      tracers, because the vocal control areas are segregated into separate nuclei. We
      inject tracers into areas afferent and efferent to the main premotor area for
      vocal production, HVC, to retrogradely and anterogradely label different classes
      of projection neurons. We optimize tissue preparation protocols to achieve high
      fluorescence contrast in the FLM and good ultrastructure in the EM (using osmium
      tetroxide). Although tracer fluorescence is lost during EM preparation, we
      localize the tracer molecules after fixation and embedding by using fluorescent
      antibodies against them. We detect signals mainly in somata and dendrites,
      allowing us to classify synapses within a single ultrathin section as belonging
      to a particular type of projection neuron. The use of our method will be to
      provide statistical information about connectivity among different neuron
      classes, and to elucidate how signals in the brain are processed and routed among
      different areas.

PMID- 20676238
TI  - Caffeine for the management of apnea in preterm infants.
AB  - Considerable uncertainty persists regarding the efficacy and safety of
      methylxanthines (caffeine, theophylline - in intravenous form named
      aminophylline) for the prevention and treatment of infant apnea. To help inform
      national guideline development in Kenya we undertook structured literature
      searches to identify current evidence on caffeine therapy for infant apnea.
      Available evidence shows that caffeine is as effective as intravenous
      theophylline (aminophylline), but is safer and easier to give and has better
      therapeutic properties. It is therefore recommended for the treatment of apnea of
      prematurity. Caffeine is also the preferred drug if clinicians plan to provide
      apnea prophylaxis. As prematurity is likely to result in more than 1 million
      deaths a year, mostly in resource-poor settings, greater efforts need to be made
      to ensure interventions such as caffeine, currently unavailable in countries such
      as Kenya, are made more widely available. 

PMID- 20676239
TI  - Synthesis of gamma-halogenated ketones via the Ce(IV)-mediated oxidative coupling
      of cyclobutanols and inorganic halides.
AB  - A straightforward method for the synthesis of gamma-halo-substituted ketones
      formed via the CAN-initiated oxidative addition of halides to 1-substituted
      cyclobutanols has been developed. This method has short reaction times, and
      provides access to a range of bromo and iodo gamma-substituted ketones in good to
      excellent yields.

PMID- 20676240
TI  - Precautionary Saving and Consumption Smoothing Across Time and Possibilities.
AB  - This paper examines how aversion to risk and aversion to intertemporal
      substitution determine the strength of the precautionary saving motive in a two
      period model with Selden/Kreps-Porteus preferences. For small risks, we derive a
      measure of the strength of the precautionary saving motive which generalizes the
      concept of "prudence" introduced by Kimball (1990b). For large risks, we show
      that decreasing absolute risk aversion guarantees that the precautionary saving
      motive is stronger than risk aversion, regardless of the elasticity of
      intertemporal substitution. Holding risk preferences fixed, the extent to which
      the precautionary saving motive is stronger than risk aversion increases with the
      elasticity of intertemporal substitution. We derive sufficient conditions for a
      change in risk preferences alone to increase the strength of the precautionary
      saving motive and for the strength of the precautionary saving motive to decline
      with wealth. Within the class of constant elasticity of intertemporal
      substitution, constant-relative risk aversion utility functions, these conditions
      are also necessary.

PMID- 20676242
TI  - Tame economists need not apply: career lessons from the 2008 canadian association
      for health services and policy research conference.
AB  - A group of student interviewers sat down with distinguished conference attendees
      at the 2008 Canadian Association for Health Services and Policy Research
      Conference. These leaders in the field shared a wealth of advice about career
      planning (don't), seizing opportunities (do) and connecting with colleagues and
      community (do often). We learned that a passion for lifelong learning, a
      willingness to get ordinary things done and a little luck go a long way towards
      career success.

PMID- 20676243
TI  - Primary Care Organization and Outcomes of an Emergency Visit among Seniors.
AB  - This study explored whether organizational characteristics of primary care
      services provided by area of residence in two Quebec regions are related to
      outcomes of an emergency department (ED) visit among seniors discharged home.
      Provincial administrative databases on a sample of seniors who made an ED visit
      and their 30-day outcomes were linked by area of residence to data from a survey
      of key informants from primary care clinics. Measures of organizational
      characteristics included three scales derived from principal components analysis
      and one theoretically derived global score that measured the degree of conformity
      to characteristics of ideal emerging primary care models. In multivariate
      analyses, adjusting for patient characteristics, patients living in areas in the
      lowest quartile for the global score had higher rates of return ED visits without
      hospitalization. Emerging primary care organizational models along the lines
      currently being pursued in Quebec may help to reduce the growing burden of ED
      care of seniors.

PMID- 20676244
TI  - Three policy issues in deciding the cost of nursing home care: provincial
      differences and how they influence elderly couples' experiences.
AB  - Nursing home care is subsidized in all Canadian provinces, but residents must
      personally contribute to the cost. This paper explores policy issues that have
      led to differences in costs of nursing home care among provinces, and how policy
      and cost differences influence the experiences of married couples when one spouse
      requires nursing home care. The paper is based on a multiple-case study of three
      Canadian provinces, each of which had a different system for determining personal
      contributions to the cost of care. Cross-case analysis of payment systems showed
      that provinces addressed three main policy issues in determining the cost of
      care: (a) what costs should be the responsibility of nursing home residents, (b)
      how subsidies should be determined and (c) how community-dwelling spouses of
      nursing home residents should be assured of an adequate income. In provinces with
      policies that resulted in higher care costs to couples and lower amounts of
      income and assets available to the community-dwelling spouses, study participants
      described reduced discretionary spending, increased financial concerns and
      perceptions of system unfairness. This paper discusses the implications of these
      three policy issues and recent related changes to provincial policies.

PMID- 20676246
TI  - Why Tolstoy Doesn't Fit Healthcare.

PMID- 20676245
TI  - Aging in atlantic Canada: service-rich and service-poor communities.
AB  - The delivery of services for seniors in Canada is increasingly complex and
      challenging. Communities across Canada age at different rates, and the forces
      underlying the differences, such as "aging in place" and migration, vary from
      community to community. We have identified two types of aging communities:
      service-rich communities, in which seniors have good health status and better
      amenities, and service-poor communities, in which seniors have poor health status
      and limited amenities. We also report on results for Atlantic Canada from a
      national study of service provisions. Three issues stand out: (a) the impact on
      communities of migration and aging in place, (b) the factors that distinguish
      service-rich and service-poor communities and (c) the conditions necessary to
      create a service-rich community. All levels of government in Atlantic Canada must
      work together to develop policies and programs that create and sustain service
      rich communities.

PMID- 20676247
TI  - The iron chancellor and the fabian.
AB  - Adam Wagstaff (2009) reports on a statistical comparison of social health
      insurance (SHI) versus tax financed (TF) health systems within the OECD. On
      average, SHI financing is more expensive than TF and yields no better health
      outcomes. It lowers overall labour force participation and reduces the share of
      the formal sector. Why, then, is interest in SHI increasing in developing
      countries?Consider the historical origins for SHI and TF. Bismarck (SHI) was a
      Prussian aristocrat; Beveridge (TF) was a socialist. TF is inherently
      egalitarian; SHI adapts readily to the preservation of inequality and privilege
      in both financing and access to care. This may be the real attraction of SHI in
      countries with highly unequal income distributions.

PMID- 20676248
TI  - More doctors or better care?
AB  - The Canadian Medical Association's More Doctors, More Care campaign seeks to
      align physician supply targets with policy decisions elsewhere in the
      Organisation for Economic Co-operation and Development (OECD). Using OECD data
      for 19 countries to assess the relationship between physician supply and
      healthcare outcomes, we have determined that there is no association between
      avoidable mortality and overall physician supply. Similarly, there is no
      relationship between avoidable mortality and general practitioners and family
      physicians per capita, specialists per capita, nurses per capita, doctors and
      nurses per capita or health expenditures per capita. These findings should move
      us to recognize that (a) more doctors will not necessarily translate into better
      healthcare outcomes for Canadians and (b) it is in Canadians' better interests
      that we instead focus on realizing opportunities to improve access to high
      quality care and to ensure that changes in physician turnover do not threaten the
      current generalist-to-specialist mix.

PMID- 20676249
TI  - Providing more choices for those who depend on ventilators.
AB  - The Winnipeg Regional Health Authority (WRHA) is building capacity in community
      care for those who depend on ventilators. Hoping to reduce pressures in acute and
      long-term care, increase the housing choices for those dependent on ventilators
      and improve the transition from one care sector to another, the WRHA, working in
      partnership with a local housing company, has designed and built unique living
      spaces tailored to the needs of ventilator-dependent clients. The project has
      caused a fundamental shift in thinking about the accommodation needs of people
      with complex medical conditions. It is also changing the WRHA's approach to care
      management across sectors and the role of allied health providers. This
      innovative initiative was recently featured in Promising Practices in Research
      Use, a series produced by the Canadian Health Services Research Foundation
      highlighting organizations that have invested their time, energy and resources to
      improve their ability to use research in the delivery of health services.
      Additional issues from the series can be found at
      http://www.chsrf.ca/promising/index_e.php.

PMID- 20676250
TI  - Measuring Integration of Cancer Services to Support Performance Improvement: The
      CSI Survey.
AB  - OBJECTIVE: To develop a measure of cancer services integration (CSI) that can
      inform clinical and administrative decision-makers in their efforts to monitor
      and improve cancer system performance. METHODS: We employed a systematic approach
      to measurement development, including review of existing cancer/health services
      integration measures, key-informant interviews and focus groups with cancer
      system leaders. The research team constructed a Web-based survey that was field-
      and pilot-tested, refined and then formally conducted on a sample of cancer care
      providers and administrators in Ontario, Canada. We then conducted exploratory
      factor analysis to identify key dimensions of CSI. RESULTS: A total of 1,769
      physicians, other clinicians and administrators participated in the survey,
      responding to a 67-item questionnaire. The exploratory factor analysis identified
      12 factors that were linked to three broader dimensions: clinical, functional and
      vertical system integration. CONCLUSIONS: The CSI Survey provides important
      insights on a range of typically unmeasured aspects of the coordination and
      integration of cancer services, representing a new tool to inform performance
      improvement efforts.

PMID- 20676251
TI  - Attitudes of Family Physicians, Specialists and Radiologists about the Use of
      Computed Tomography and Magnetic Resonance Imaging in Ontario.
AB  - BACKGROUND: Despite efforts to reduce wait times for computed tomography (CT) and
      magnetic resonance imaging (MRI) in Ontario, little is known about physicians'
      attitudes regarding contemporary patterns of CT and MRI scan use in this
      province. METHODS: We interviewed 19 Ontario family physicians, specialists and
      radiologists from diverse settings between November 2006 and April 2007. Our
      detailed written notes were independently reviewed to identify major recurring
      themes. RESULTS: MAJOR THEMES WERE GROUPED UNDER TWO CATEGORIES: (a) non-clinical
      reasons for ordering CT and MRI ("defensive ordering," indeterminate imaging
      reports, patient demand, supply-induced demand, marked variation in ordering
      practices) and (b) communication among groups of physicians (increasing isolation
      between clinicians and radiologists; specialists and family physicians working in
      silos). CONCLUSION: These interviews revealed infrequent communication among
      physician groups and marked variations in ordering practices that are often
      driven by a number of non-clinical factors, such as fear of litigation and
      patient demand. Recent increases in CT and MRI capacity may not be leading to
      better care for patients. Our findings, however, are very preliminary and require
      validation in other studies.

PMID- 20676252
TI  - The Use of Research Evidence in Two International Organizations' Recommendations
      about Health Systems.
AB  - BACKGROUND: Little is known about the extent to which research evidence informs
      the development of recommendations by international organizations. METHODS: We
      identified specific World Health Organization (WHO) and World Bank
      recommendations on five topics (contracting, healthcare financing, health human
      resources, tuberculosis control and tobacco control), catalogued the related
      systematic reviews and assessed the recommendations to determine their
      consistency with the systematic reviews that were available at the time of their
      formulation. FINDINGS: Only two of the eight publications examined were found to
      cite systematic reviews, and only five of 14 WHO and two of seven World Bank
      recommendations were consistent with both the direction and nature of effect
      claims from systematic reviews. Ten of 14 WHO and five of seven World Bank
      recommendations were consistent with the direction of effect claims only.
      CONCLUSION: WHO and the World Bank - working with donor agencies and national
      governments - can improve their use of (or at least, their reporting about their
      use of) research evidence. Decision-makers and clinicians should critically
      evaluate the quality and local applicability of recommendations from any source,
      including international organizations, prior to their implementation.

PMID- 20676253
TI  - Reasons for self-reported unmet healthcare needs in Canada: a population-based
      provincial comparison.
AB  - In this study, we compare self-perceived unmet need across Canadian provinces and
      assess how the reasons for unmet need - problems with availability, accessibility
      and acceptability - vary. This cross-sectional study uses data from the Canadian
      Community Health Survey (2.1) conducted in 2003. Overall, 11.7% perceived having
      had unmet healthcare needs in the previous 12 months. The adjusted provincial
      rates varied from 13.3% in Manitoba to 7.8% in Prince Edward Island. Among those
      reporting unmet health service needs, the leading reason was problems of
      availability of services (54.9%), followed by acceptability (42.8%) and
      accessibility related to cost or transportation (12.7%). Unmet need due to
      problems of availability was most likely in Quebec, Newfoundland and Manitoba,
      while Alberta and British Columbia had the highest likelihood of unmet need due
      to accessibility problems. Those in British Columbia, Saskatchewan and Manitoba
      were more likely to report problems of acceptability. The reasons for unmet need
      vary across provinces, with each reason having different policy implications.

PMID- 20676255
TI  - Diverticular disease.

PMID- 20676254
TI  - David a. Margolin, m.d.

PMID- 20676256
TI  - Epidemiology and pathophysiology of diverticular disease.
AB  - Diverticular disease is common and thought to result from structural
      abnormalities of the colonic wall, disordered intestinal motility, or
      deficiencies of dietary fiber. Signs and symptoms of inflammation include fever,
      abdominal pain, and leukocytosis.

PMID- 20676257
TI  - Imaging update: acute colonic diverticulitis.
AB  - Because the incidence of colonic diverticulosis is high in the general
      population, incidental asymptomatic diverticulosis is commonly seen on radiology
      imaging studies. However, diagnostic imaging performed specifically for
      diverticular disease is essentially limited to imaging of suspected acute colonic
      diverticulitis (ACD) and its complications. The clinical diagnosis of ACD can be
      challenging, and imaging has become an essential tool to aid in diagnosis, assess
      severity of disease, and aid in treatment planning. Computed tomography (CT) has
      replaced contrast enema as the imaging procedure of choice for diverticulitis.
      Ultrasound has also been successfully used for diagnosis, and magnetic resonance
      imaging (MRI) has significant potential as a radiation-free imaging test for
      acute colonic diverticulitis.

PMID- 20676258
TI  - The medical and nonoperative treatment of diverticulitis.
AB  - The success of medical management for diverticular disease depends on the
      patient's presentation and degree of response to treatment. The patient's
      presentation can be grouped into categories using classification systems such as
      the modified Hinchey system. Clinical presentation and diagnostic studies help to
      group patients. Mild disease can often be managed with oral antibiotics as an
      outpatient; more severe disease requires hospitalization, bowel rest, and
      intravenous antibiotics. Interventions such as percutaneous drainage of
      associated abscesses may allow successful medical management. Probiotics and
      antiinflammatories may have a supportive role. Indications for elective
      resections are discussed.

PMID- 20676259
TI  - Emergency management of diverticulitis.
AB  - The most common indications for emergency operative intervention in the treatment
      of sigmoid diverticulitis are peritonitis and failure of medical therapy. Primary
      resection and diversion (Hartmann's procedure) followed by delayed colostomy
      closure is the current standard of emergency surgical care. Guidelines for best
      operative strategy, however, remain controversial and continue to evolve based on
      recent comparative reviews of surgical outcomes. Primary resection and
      anastomosis with or without proximal diversion and laparoscopic lavage are
      alternatives to Hartmann's procedure that may provide an improved outcome in
      properly selected patients. Ongoing changes in the historical paradigm of the
      surgical approach to this disease mandate the need for large multicentered
      prospective randomized trials to determine the best surgical strategy under
      emergent conditions for the treatment of diverticulitis. The current literature
      is reviewed with suggestions for a management algorithm.

PMID- 20676260
TI  - Timing of elective surgery for diverticular disease.
AB  - The timing of elective surgery for the treatment of diverticular disease is
      constantly evolving. Historically, the indications for elective surgery were
      relatively consistent. It was recommended that patients undergo elective
      resection after two documented attacks of uncomplicated diverticulitis or after
      one attack of complicated diverticulitis in which the patient did not require
      emergent surgery. There were some exceptions to these guidelines; people <50
      years old could undergo elective resection after their first attack, and patients
      who had previous solid organ transplants could undergo resection after a single
      attack. In this article, the author updates the data regarding the timing of
      surgery in elective diverticular disease and challenges surgical dogma.

PMID- 20676261
TI  - Laparoscopic management of diverticular disease.
AB  - Despite its potential advantages, laparoscopic management of diverticular disease
      is currently performed by a minority of surgeons on a small group of patients.
      However, the role for laparoscopy in diverticular disease continues to develop.
      At present, adequate evidence exists for the routine use of laparoscopy for
      uncomplicated diverticular disease. Complicated disease, including fistulizing
      disease and free perforation requires additional expertise and study. As the
      experience grows among individual surgeons and institutions, it can be expected
      that the complication and conversion rates will continue to decline allowing even
      further evolution of laparoscopy for the treatment of this challenging disease
      process.

PMID- 20676262
TI  - Management of diverticular hemorrhage.
AB  - Diverticular hemorrhage is the most common cause of lower gastrointestinal
      bleeding in Westernized cultures. Fortunately, the majority of diverticular
      bleeds will spontaneously resolve; however, 20% of patients will require
      therapeutic interventions to obtain hemostasis. The diagnostic and therapeutic
      options for the management of diverticular hemorrhage are discussed.

PMID- 20676265
TI  - Human responding on random-interval schedules of response-cost punishment: the
      role of reduced reinforcement density.
AB  - An experiment with adult humans investigated the effects of response-contingent
      money loss (response-cost punishment) on monetary-reinforced responding. A yoked
      control procedure was used to separate the effects on responding of the response
      cost contingency from the effects of reduced reinforcement density. Eight adults
      pressed buttons for money on a three-component multiple reinforcement schedule.
      During baseline, responding in all components produced money gains according to a
      random-interval 20-s schedule. During punishment conditions, responding during
      the punishment component conjointly produced money losses according to a random
      interval schedule. The value of the response-cost schedule was manipulated across
      conditions to systematically evaluate the effects on responding of response-cost
      frequency. Participants were assigned to one of two yoked-control conditions. For
      participants in the Yoked Punishment group, during punishment conditions money
      losses were delivered in the yoked component response independently at the same
      intervals that money losses were produced in the punishment component. For
      participants in the Yoked Reinforcement group, responding in the yoked component
      produced the same net earnings as produced in the punishment component. In 6 of 8
      participants, contingent response cost selectively decreased response rates in
      the punishment component and the magnitude of the decrease was directly related
      to the punishment schedule value. Under punishment conditions, for participants
      in the Yoked Punishment group response rates in the yoked component also
      decreased, but the decrease was less than that observed in the punishment
      component, whereas for participants in the Yoked Reinforcement group response
      rates in the yoked component remained similar to rates in the no-punishment
      component. These results provide further evidence that contingent response cost
      functions similarly to noxious punishers in that it appears to suppress
      responding apart from its effects on reinforcement density.

PMID- 20676266
TI  - Risky choice in pigeons and humans: a cross-species comparison.
AB  - Pigeon and human subjects were given repeated choices between variable and
      adjusting delays to token reinforcement that titrated in relation to a subject's
      recent choice patterns. Indifference curves were generated under two different
      procedures: immediate exchange, in which a token earned during each trial was
      exchanged immediately for access to the terminal reinforcer (food for pigeons,
      video clips for humans), and delayed exchange, in which tokens accumulated and
      were exchanged after 11 trials. The former was designed as an analogue of
      procedures typically used with nonhuman subjects, the latter as an analogue to
      procedures typically used with human participants. Under both procedure types,
      different variable-delay schedules were manipulated systematically across
      conditions in ways that altered the reinforcer immediacy of the risky option.
      Under immediate-exchange conditions, both humans and pigeons consistently
      preferred the variable delay, and indifference points were generally ordered in
      relation to relative reinforcer immediacies. Such risk sensitivity was greatly
      reduced under delayed-exchange conditions. Choice and trial-initiation response
      latencies varied directly with indifference points, suggesting that local
      analyses may provide useful ancillary measures of reinforcer value. On the whole,
      the results indicate that modifying procedural features brings choices of pigeons
      and humans into better accord, and that human-nonhuman differences on risky
      choice procedures reported in the literature may be at least partly a product of
      procedural differences.

PMID- 20676267
TI  - Stimulus effects on local preference: stimulus-response contingencies, stimulus
      food pairing, and stimulus-food correlation.
AB  - Four pigeons were trained in a procedure in which concurrent-schedule food ratios
      changed unpredictably across seven unsignaled components after 10 food
      deliveries. Additional green-key stimulus presentations also occurred on the two
      alternatives, sometimes in the same ratio as the component food ratio, and
      sometimes in the inverse ratio. In eight experimental conditions, we varied the
      contingencies surrounding these additional stimuli: In two conditions, stimulus
      onset and offset were noncontingent; in another two, stimulus onset was
      noncontingent, and offset was response contingent. In four conditions, both
      stimulus onset and offset were contingent, and in two of these conditions the
      stimulus was simultaneously paired with food delivery. Sensitivity to component
      food ratios was significantly higher when stimulus onset was response contingent
      compared to when it was noncontingent. Choice changes following food delivery
      were similar in all eight conditions. Choice changes following stimuli were
      smaller than those following food, and directionally were completely determined
      by the food-ratio:stimulus-ratio correlation, not by the stimulus contingency nor
      by whether the stimulus was paired with food or not. These results support the
      idea that conditional reinforcers may best be viewed as signals for next-food
      location rather than as stimuli that have acquired hedonic value, at least when
      the signals are differential with respect to future conditions.

PMID- 20676268
TI  - A runs-test algorithm: contingent reinforcement and response run structures.
AB  - Four rats' choices between two levers were differentially reinforced using a runs
      test algorithm. On each trial, a runs-test score was calculated based on the last
      20 choices. In Experiment 1, the onset of stimulus lights cued when the runs
      score was smaller than criterion. Following cuing, the correct choice was
      occasionally reinforced with food, and the incorrect choice resulted in a
      blackout. Results indicated that this contingency reduced sequential dependencies
      among successive choice responses. With one exception, subjects' choice rule was
      well described as biased coin flipping. In Experiment 2, cuing was removed and
      the reinforcement criterion was changed to a percentile score based on the last
      20 reinforced responses. The results replicated those of Experiment 1 in
      successfully eliminating first-order dependencies in all subjects. For 2
      subjects, choice allocation was approximately consistent with nonbiased coin
      flipping. These results suggest that sequential dependencies may be a function of
      reinforcement contingency.

PMID- 20676269
TI  - A paradigm for operant conditioning in blow flies (Phormia terrae novae Robineau
      Desvoidy, 1830).
AB  - An operant conditioning situation for the blow fly (Protophormia terrae novae) is
      described. Individual flies are trained to enter and reenter a hole as the
      operant response. Only a few sessions of contingent reinforcement are required to
      increase response rates. When the response is no longer followed by food, the
      rate of entering the hole decreases. Control procedures revealed that rate of
      responding is not a simple overall result of feeding or of aging. The flies
      entered into the hole only if the response was required to obtain the food.

PMID- 20676270
TI  - The dynamics of the law of effect: a comparison of models.
AB  - Dynamical models based on three steady-state equations for the law of effect were
      constructed under the assumption that behavior changes in proportion to the
      difference between current behavior and the equilibrium implied by current
      reinforcer rates. A comparison of dynamical models showed that a model based on
      Navakatikyan's (2007) two-component functions law-of-effect equations performed
      better than models based on Herrnstein's (1970) and Davison and Hunter's (1976)
      equations. Navakatikyan's model successfully described the behavioral dynamics in
      schedules with negative-slope feedback functions, concurrent variable-ratio
      schedules, Vaughan's (1981) melioration experiment, and experiments that arranged
      equal, and constant-ratio unequal, local reinforcer rates.

PMID- 20676272
TI  - Delayed reinforcement of operant behavior.
AB  - The experimental analysis of delay of reinforcement is considered from the
      perspective of three questions that seem basic not only to understanding delay of
      reinforcement, but, also, by implication, the contributions of temporal relations
      between events to operant behavior. The first question is whether effects of the
      temporal relation between responses and reinforcers can be isolated from other
      features of the environment that often accompany delays, such as stimuli or
      changes in the temporal distribution or rate of reinforcement. The second
      question is that of the effects of delays on operant behavior. Beyond the common
      denominator of a temporal separation between reinforcers and the responses that
      produce them, delay of reinforcement procedures differ from one another along
      several dimensions, making delay effects circumstance dependent. The final
      question is one of interpreting delay of reinforcement effects. It centers on the
      role of the response-reinforcer temporal relation in the context of other,
      concurrently operating behavioral processes.

PMID- 20676274
TI  - Thiazolidinediones and cardiovascular risk - a question of balance.
AB  - BACKGROUND: Several recent meta-analyses of adverse event data from randomized
      controlled trials with rosiglitazone reveal a possible association between this
      thiazolidinedione and an increased risk of ischemic myocardial events. This has
      led to debate on the overall clinical benefit of glitazone therapy for type 2
      diabetes. Pioglitazone, on the other hand, has the most extensive cardiovascular
      outcomes database of all current glucose-lowering therapies, including a large
      prospective randomized controlled trial designed specifically to assess
      cardiovascular outcomes (PROactive). The available data suggest that pioglitazone
      is associated with a reduction in macrovascular risk. AIMS: In this review, we
      highlight some of the key factors that need to be considered when assessing the
      net clinical benefit of thiazolidinediones, focussing on both class effects and
      those specific to either rosiglitazone or pioglitazone. RESULTS: For pioglitazone
      there appears to be no increase in the risk of overall macrovascular events and
      no adverse clinical consequences of developing signs of heart failure.
      Furthermore, there is good evidence of significant benefit regarding the
      composite of death, MI or stroke. CONCLUSION: The benefits seen with pioglitazone
      appear to outweigh the risks.

PMID- 20676275
TI  - Iatrogenic QT Abnormalities and Fatal Arrhythmias: Mechanisms and Clinical
      Significance.
AB  - Severe and occasionally fatal arrhythmias, commonly presenting as Torsade de
      Pointes [TdP] have been reported with Class III-antiarrhythmics, but also with
      non-antiarrhythmic drugs. Most cases result from an action on K(+) channels
      encoded by the HERG gene responsible for the IKr repolarizing current, leading to
      a long QT and repolarization abnormalities. The hydrophobic central cavity of the
      HERG-K+ channels, allows a large number of structurally unrelated drugs to bind
      and cause direct channel inhibition. Some examples are dofetilide, quinidine,
      sotalol, erythromycin, grepafloxacin, cisapride, dolasetron, thioridazine,
      haloperidol, droperidol and pimozide. Other drugs achieve channel inhibition
      indirectly by impairing channel traffic from the endoplasmic reticulum to the
      cell membrane, decreasing channel membrane density (pentamidine, geldalamicin,
      arsenic trioxide, digoxin, and probucol). Whereas, ketoconazole, fluoxetine and
      norfluoxetine induce both direct channel inhibition and impaired channel
      trafficking. Congenital long QT syndrome, subclinical ion-channel mutations,
      subjects and relatives of subjects with previous history of drug-induced long QT
      or TdP, dual drug effects on cardiac repolarization [long QT plus increased QT
      dispersion], increased transmural dispersion of repolarization and T wave
      abnormalities, use of high doses, metabolism inhibitors and/or combinations of QT
      prolonging drugs, hypokalemia, structural cardiac disease, sympathomimetics,
      bradycardia, women and older age, have been shown to increase the risk for
      developing drug-induced TdP. Because most of these reactions are preventable,
      careful evaluation of risk factors and increased knowledge of drugs use
      associated with repolarization abnormalities is strongly recommended. Future
      genetic testing and development of practical and simple provocation tests are in
      route to prevent iatrogenic TdP.

PMID- 20676276
TI  - Coronary risk assessment and management options in chronic kidney disease
      patients prior to kidney transplantation.
AB  - Cardiovascular disease remains the most important cause of morbidity and
      mortality among kidney transplant recipients. Nearly half the deaths in
      transplanted patients are attributed to cardiac causes and almost 5% of these
      deaths occur within the first year after transplantation. The ideal strategies to
      screen for coronary artery disease (CAD) in chronic kidney disease patients who
      are evaluated for kidney transplantation (KT) remain controversial. The American
      Society of Transplantation recommends that patients with diabetes, prior history
      of ischemic heart disease or an abnormal ECG, or age >/=50 years should be
      considered as high-risk for CAD and referred for a cardiac stress test and only
      those with a positive stress test, for coronary angiography. Despite these
      recommendations, vast variations exist in the way these patients are screened for
      CAD at different transplant centers. The sensitivity and specificity of
      noninvasive cardiac tests in CKD patients is much lower than that in the general
      population. This has prompted the use of direct diagnostic cardiac
      catheterization in high-risk patients in several transplant centers despite the
      risks associated with this invasive procedure. No large randomized controlled
      trials exist to date that address these issues. In this article, we review the
      existing literature with regards to the available data on cardiovascular risk
      screening and management options in CKD patients presenting for kidney
      transplantation and outline a strategy for approach to these patients.

PMID- 20676277
TI  - Current management of traumatic rupture of the descending thoracic aorta.
AB  - Traumatic rupture of the descending thoracic aorta remains a leading cause of
      death following major blunt trauma. Management has evolved from uniformly
      performing emergent open repair with clamp and sew technique to include open
      repair with mechanical circulatory support, medical management and most recently,
      endovascular repair. This latter approach appears, in the short term, to be
      associated with perhaps better outcome, but long term data is still accruing.
      While an attractive option, there are specific anatomic and physiologic factors
      to be considered in each individual case.

PMID- 20676278
TI  - Toll-like receptors and myocardial ischemia/reperfusion, inflammation, and
      injury.
AB  - Cardiac ischemia/reperfusion (I/R) injury occurs in several important clinical
      contexts including percutaneous coronary interventions for acute myocardial
      ischemia, cardiac surgery in the setting of cardiopulmonary bypass, and cardiac
      transplantation. While the pathogenesis of I/R injury in these settings is
      multifactorial, it is clear that activation of the innate immune system and the
      resultant inflammatory response are important components of I/R injury. Toll-like
      receptor 4 (TLR4), originally identified as the sensor for bacterial
      lipopolysaccharide (LPS), has also been shown to serve as a sensor for endogenous
      molecules released from damaged or ischemic tissues. Accordingly, recent findings
      have demonstrated that TLR4 not only plays a central role as a mediator of
      cardiac dysfunction in sepsis, but also serves as a key mediator of myocardial
      injury and inflammation in the setting of I/R. Furthermore, TLR4 may play a role
      in the development of atherosclerotic lesions. Other studies have implicated TLR4
      in the adverse remodeling that may occur after ischemic myocardial injury. This
      emerging body of literature, which is reviewed here, has provided new insight
      into the early molecular events that mediate myocardial injury and dysfunction in
      the setting of I/R injury.

PMID- 20676280
TI  - Triglycerides and cardiovascular risk.
AB  - In 1996 a meta-analysis was published showing that an increase in plasma
      triglyceride (TG) levels was associated with an increase in CHD risk, even after
      adjustment for high density lipoprotein cholesterol (HDL-C) levels. Very
      recently, two studies were published that further extent the early observation
      and showed the importance of nonfasting plasma triglyceride (TG) levels in the
      prediction of risk on coronary heart disease (CHD). In the current review we have
      summarized all available evidence obtained in clinical studies showing that
      treatment guidelines should reconsider to include nonfasting TG in their risk
      assessments as nonfasting TG levels may better predict CVD risk.

PMID- 20676281
TI  - Diminished renal function and the incidence of heart failure.
AB  - Heart failure is one of the most common, costly, disabling and deadly diseases.
      During the last decade, several different indices reflecting renal function such
      as creatinine-based glomerular filtration rate, circulating levels of cystatin C
      and low-grade albuminuria have been demonstrated to be independent risk factors
      for heart failure. This review summarizes our current knowledge of the
      relationship between diminished renal function and the incidence of heart failure
      in the community, and also in individuals with increased risk of heart failure
      such as patients with overt cardiovascular disease, hypertension or diabetes.
      This review will also put forward important areas of future research in this
      field.

PMID- 20676279
TI  - The GH/IGF-1 Axis and Heart Failure.
AB  - The growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis regulates
      cardiac growth, stimulates myocardial contractility and influences the vascular
      system. The GH/IGF-1 axis controls intrinsic cardiac contractility by enhancing
      the intracellular calcium availability and regulating expression of contractile
      proteins; stimulates cardiac growth, by increasing protein synthesis; modifies
      systemic vascular resistance, by activating the nitric oxide system and
      regulating non-endothelial-dependent actions. The relationship between the GH/IGF
      1 axis and the cardiovascular system has been extensively demonstrated in
      numerous experimental studies and confirmed by the cardiac derangements secondary
      to both GH excess and deficiency. Several years ago, a clinical non-blinded study
      showed, in seven patients with idiopathic dilated cardiomyopathy and chronic
      heart failure (CHF), a significant improvement in cardiac function and structure
      after three months of treatment with recombinant GH plus standard therapy for
      heart failure. More recent studies, including a small double-blind placebo
      controlled study on GH effects on exercise tolerance and cardiopulmonary
      performance, have shown that GH benefits patients with CHF secondary to both
      ischemic and idiopathic dilated cardiomyopathy. However, conflicting results
      emerge from other placebo-controlled trials. These discordant findings may be
      explained by the degree of CHF-associated GH resistance. In conclusion, we
      believe that more clinical and experimental studies are necessary to exactly
      understand the mechanisms that determine the variable sensitivity to GH and its
      positive effects in the failing heart.

PMID- 20676282
TI  - Cardiac amyloidosis responding to bortezomib: case report and review of
      literature.
AB  - We report a case of a 53-year old patient with symptoms of congestive heart
      failure in whom a restrictive cardiomyopathy and a kappa-chain monoclonal
      gammopahty were diagnosed. Treatment with eight cycles of Bortezomib, a
      proteasome inhibitor, resulted in a significant regression of myocardial amyloid
      deposition and a notable clinical and hemodynamic improvement. Over the last few
      years, the management of cardiac amyloidosis has taken advantage of many of the
      advances of the chemotherapeutic regimens, as well as the wider availability of
      stem cell transplantation. The management of cardiac amyloidosis is also expected
      to evolve and improve with the better understanding of the specific mechanisms of
      amyloidogenesis and myocardial deposition. This will probably make certain
      molecules targeting specific sites in this process, as potentially effective and
      minimally toxic compared therapy with the currently used ones. In this article,
      we describe one of the first reported cases of cardiac amyloidosis, successfully
      treated with Bortezomib. We describe and discuss the mechanisms of action of
      Bortezomib and provide a detailed review of cardiac amyloidosis, from
      pathophysiology to diagnosis and treatment.

PMID- 20676283
TI  - Clinical applications for cardiovascular magnetic resonance imaging at 3 tesla.
AB  - Cardiovascular magnetic resonance (CMR) imaging has evolved rapidly and is now
      accepted as a powerful diagnostic tool with significant clinical and research
      applications. Clinical 3 Tesla (3 T) scanners are increasingly available and
      offer improved diagnostic capabilities compared to 1.5 T scanners for perfusion,
      viability, and coronary imaging. Although technical challenges remain for cardiac
      imaging at higher field strengths such as balanced steady state free precession
      (bSSFP) cine imaging, the majority of cardiac applications are feasible at 3 T
      with comparable or superior image quality to that of 1.5 T. This review will
      focus on the benefits and limitations of 3 T CMR for common clinical applications
      and examine areas in development for potential clinical use.

PMID- 20676284
TI  - Myocardial energetics in left ventricular hypertrophy.
AB  - The heart carries out its pumping function by converting the chemical energy
      stored in fatty acids and glucose into the mechanical energy of actin-myosin
      interaction of myofibrils. Development of congestive heart failure is usually
      preceded by a period of compensated left ventricular hypertrophy (LVH) and
      alterations in myocardial bioenergetics have been considered to play an important
      role in this transition. Myocardial energetic state that is reflected by the
      ratio of Phosphocreatine to Adenosine Triphosphate (PCr/ATP) is significantly
      decreased in hearts with LVH. The severity of this abnormality is linearly
      related to the severity of cardiac hypertrophy as well as left ventricular (LV)
      dysfunction, and is independent of a persistent myocardial ischemia. The decrease
      in PCr/ATP is accompanied by a decrease in creatine kinase flux and alterations
      in substrate utilization in LVH hearts. Moreover, there is a profound
      heterogeneity in alterations in myocardial energy metabolism in hearts with post
      infarction hypertrophy with the most severe abnormality present in the inner
      layers of the periscar border zone (BZ). This review will discuss various aspects
      of myocardial energetics in animal models of three different types of LVH
      (pressure-overload, volume overload and post-infarction) with a brief description
      of myocardial energetics in humans with LVH.

PMID- 20676285
TI  - Tail docking and ear cropping - A comment.

PMID- 20676286
TI  - Appointments to keep.

PMID- 20676287
TI  - An ethicist's commentary on whether veterinarians should condemn activist attacks
      on confinement agriculture?

PMID- 20676288
TI  - Hind-limb paresis in a dog with paralumbar solitary T-cell lymphoma.
AB  - A 2-year-old, neutered, male golden retriever was referred to the Ontario
      Veterinary College, with a 6-week history of hind limb weakness and back pain.
      Magnetic resonance imaging of the lumbar vertebral column, and histopathology and
      immunohistochemistry following euthanasia identified an uncommon solitary T-cell
      lymphoma in the paralumbar area.

PMID- 20676290
TI  - Feline urate urolithiasis.
AB  - This retrospective case control study describes associations between feline urate
      urolithiasis and breed, age, gender, and urine composition. Data from cases of
      feline uroliths submitted to the Canadian Veterinary Urolith Centre (CVUC)
      between February 2, 1998 and July 7, 2007 were reviewed. There were 10 083 feline
      uroliths examined, including 385 ammonium urate, 13 uric acid, and 21 mixed
      struvite/urate uroliths. The Egyptian Mau, Birman, and Siamese breeds were
      significantly predisposed to urate urolithiasis [odds ratio (OR) = 118, 95%
      confidence interval (CI) = 38.2 to 510, P < 0.001], (OR = 9.1, 95% CI = 2.0 to
      32, P < 0.001) and (OR = 3.9, 95% CI = 2.5 to 5.9, P < 0.001), respectively.
      Urate urolithiasis was more frequent in younger cats (mean age 6.3 versus 7.1 y
      in cats with other uroliths, P < 0.0001) and in male cats (P = 0.024). The
      association between Egyptian Maus and urate urolithiasis was remarkable. The
      association in Siamese cats is consistent with prior reports, and the association
      with Birman cats requires further study.

PMID- 20676289
TI  - Spinal cord injury I: A synopsis of the basic science.
AB  - Substantial knowledge has been gained in the pathological findings following
      naturally occurring spinal cord injury (SCI) in dogs and cats. The molecular
      mechanisms involved in failure of neural regeneration within the central nervous
      system, potential therapeutics including cellular transplantation therapy, neural
      plasticity, and prognostic indicators of recovery from SCI have been studied.
      This 2-part review summarizes 1) basic science perspectives regarding treating
      and curing spinal cord injury, 2) recent studies that shed light on prognosis and
      recovery from SCI, 3) current thinking regarding standards of care for dogs with
      SCI, 4) experimental approaches in the laboratory setting, and 5) current
      clinical trials being conducted in veterinary medicine. Part I presents timely
      information on the pathophysiology of spinal cord injury, challenges associated
      with promoting regeneration of neurons of the central nervous system, and
      experimental approaches aimed at developing treatments for spinal cord injury.

PMID- 20676291
TI  - Limb-sparing surgery using tantalum metal endoprosthesis in a dog with
      osteosarcoma of the distal radius.
AB  - A 5-year-old, male neutered, mixed breed dog was presented for left forelimb
      lameness and swelling over the left distal radius. A primary bone tumor of the
      distal radius was diagnosed and limb-sparing surgery of the left forelimb was
      performed using a tantalum metal-DCP endoprosthesis. Post-operative
      histopathology confirmed osteosarcoma.

PMID- 20676292
TI  - Intranasal naltrexone and atipamezole for reversal of white-tailed deer
      immobilized with carfentanil and medetomidine.
AB  - Carfentanil and medetomidine were used to immobilize 8 captive female white
      tailed deer (Odocoileus virginianus) using mean dosages [+/- standard deviation
      (s)] of 14.2 +/- 1.11 microg/kg carfentanil and 17.8 +/- 2.03 microg/kg of
      medetomidine. Deer were reversed by intranasally or intramuscularly administered
      naltrexone and atipamezole. Dosages of carfentanil and medetomidine proved
      reliable for immobilization of most, but not all deer, with a mean induction time
      of 13.3 +/- 3.13 min. Effective and reliable immobilization will require higher
      dosages of carfentanil and possibly medetomidine than were used in this study. No
      significant differences in recovery times were observed for deer given reversal
      agents intranasally (9.45 +/- 5.37 min) versus intramuscularly (7.60 +/- 4.42
      min). Naltrexone and atipamezole can be administered intranasally at 1.5 mg/kg
      and 0.1 mg/kg, respectively to safely and quickly reverse the effects of
      carfentanil and medetomidine in immobilized white-tailed deer. This route could
      potentially be useful for other reversal agents.

PMID- 20676293
TI  - Silicone elastomer sling for rectal prolapse in cats.
AB  - This study reports 2 cases of recurrent rectal prolapse secondary to anal
      abnormality in cats. In both cases the anus was wide, leading to a rectal mucosal
      prolapse during defecation. A silicone elastomer sling was introduced around the
      anus, and the rectal prolapse was definitively resolved.

PMID- 20676294
TI  - Gastrointestinal obstruction caused by a radiolucent foreign body in a green
      iguana (Iguana Iguana).
AB  - This report describes an intestinal obstruction in a green iguana (Iguana
      iguana). The patient was presented with vomiting and subtle signs of abdominal
      pain. Radiographs and ultrasound imaging did not reveal any abnormalities. A
      coeliotomy was performed and a 30-cm piece of absorbent cotton was removed
      surgically from the large intestine.

PMID- 20676295
TI  - Peracute selenium toxicosis followed by sudden death in growing and finishing
      pigs.
AB  - Fattening pigs (n = 751) showed progressive apathy, paralysis, and sudden death
      after accidental ingestion of excessive concentrations of selenium in mineral
      feed. Selenium concentrations of 1.09 to 1.32 mg/L in the serum confirmed the
      diagnosis. Within 3 d all pigs had died spontaneously or were euthanized due to
      the grave prognosis and on welfare grounds.

PMID- 20676296
TI  - Comparative imaging of spinal extradural lymphoma in a Bordeaux dog.
AB  - A lumbar extradural lymphoma compressing the spinal cord was identified on
      contrast enhanced computed tomography (CT) and magnetic resonance imaging (MRI)
      images in a 4-year-old Bordeaux dog presented with posterior paresis. A
      significant paravertebral extension was only clearly defined on contrast MRI
      images; therefore, MRI was more useful than CT in imaging of spinal extradural
      lymphoma in this dog.

PMID- 20676297
TI  - Primary epitheliotropic intestinal T-cell lymphoma as a cause of diarrhea in a
      horse.
AB  - A 25-year-old Appaloosa gelding was evaluated for chronic weight loss and
      diarrhea. A clinical diagnosis of protein loosing enteropathy was made and the
      gelding was euthanized. Histology revealed neoplastic lymphocytes infiltrating
      the mucosa of the small and large intestine. Immunohistochemistry was positive
      for CD3, consistent with epitheliotropic T-cell lymphoma.

PMID- 20676298
TI  - The effect of storage temperature on the accuracy of a cow-side test for ketosis.
AB  - The objective of this study was to assess the effect of storage conditions on the
      accuracy of a milk test strip for ketosis. Storage at 21 degrees C for up to 18
      wk had little effect on accuracy for diagnosis and classification of subclinical
      ketosis.

PMID- 20676299
TI  - A case of splenic torsion with progressive anemia and thrombocytopenia.
AB  - A 4-year-old male, castrated Saint Bernard was evaluated for acute onset of
      lethargy and collapse. Moderately severe anemia and splenomegaly were noted.
      Immune mediated hemolytic anemia was initially suspected. Abdominal ultrasound
      demonstrated an absence of splenic blood flow. Splenic torsion was confirmed on
      exploratory laparotomy and a splenectomy was performed.

PMID- 20676300
TI  - Reducing error in radiographic interpretation.

PMID- 20676301
TI  - Craniectomy and orbitectomy in dogs and cats.

PMID- 20676302
TI  - Toward reconstructing spike trains from large-scale calcium imaging data.
AB  - Neural activity can be captured by state-of-the-art optical imaging methods
      although the analysis of the resulting data sets is often manual and not
      standardized. Therefore, laboratories using large-scale calcium imaging eagerly
      await software toolboxes that can automate the process of identifying cells and
      inferring spikes. An algorithm proposed and implemented in a recent paper by
      Mukamel et al. [Neuron 63, 747-760 (2009)] used independent component analysis
      and offers significant improvements over conventional methods. The approach
      should be widely applicable, as tested with data obtained from the mouse
      cerebellum, neocortex, and spinal cord. The emergence of analysis tools in
      parallel with the rapid advances in optical imaging is an exciting development
      that will stimulate new discoveries and further elucidate the functions of neural
      circuits.

PMID- 20676303
TI  - Systems genetics: the added value of gene expression.
AB  - Understanding causal relationships between genotypes and phenotypes is a long
      standing aim in genetics. In addition to high-throughput technologies that allow
      the measurement of many DNA variants it is possible to measure gene expression in
      specific tissues using array technology. "Systems genetics" is an emerging
      discipline that combines dense data on genotypes, gene expression, and outcome
      phenotypes to answer fundamental questions about causal pathways from genotype to
      phenotype. A recent paper by Chen et al. [Mol. Syst. Biol. 5, 310 (2009)]
      addressed the question of whether relative levels of mRNA expression help to
      elucidate causal paths from genotype to phenotype, using drug resistance in yeast
      as a model. The authors show that data on genetic markers and on gene expression,
      measured in a drug-free environment, can be combined to predict the growth of a
      yeast strain in the presence of a drug. They argue that their prediction can be
      used to identify causal pathways and for a subset of the genes used in
      prediction, the authors demonstrate that these genes cause an effect on drug
      sensitivity by deleting the gene or overexpressing it or swapping alleles between
      strains of yeast. This approach can also be applied to other species, including
      humans, and may become a tool in the study of personalized medicine.

PMID- 20676304
TI  - Multiphase flow models of biogels from crawling cells to bacterial biofilms.
AB  - This article reviews multiphase descriptions of the fluid mechanics of cytoplasm
      in crawling cells and growing bacterial biofilms. These two systems involve gels,
      which are mixtures composed of a polymer network permeated by water. The fluid
      mechanics of these systems is essential to their biological function and
      structure. Their mathematical descriptions must account for the mechanics of the
      polymer, the water, and the interaction between these two phases. This review
      focuses on multiphase flow models because this framework is natural for including
      the relative motion between the phases, the exchange of material between phases,
      and the additional stresses within the network that arise from nonspecific
      chemical interactions and the action of molecular motors. These models have been
      successful in accounting for how different forces are generated and transmitted
      to achieve cell motion and biofilm growth and they have demonstrated how emergent
      structures develop though the interactions of the two phases. A short description
      of multiphase flow models of tumor growth is included to highlight the
      flexibility of the model in describing diverse biological applications.

PMID- 20676305
TI  - How protein materials balance strength, robustness, and adaptability.
AB  - Proteins form the basis of a wide range of biological materials such as hair,
      skin, bone, spider silk, or cells, which play an important role in providing key
      functions to biological systems. The focus of this article is to discuss how
      protein materials are capable of balancing multiple, seemingly incompatible
      properties such as strength, robustness, and adaptability. To illustrate this, we
      review bottom-up materiomics studies focused on the mechanical behavior of
      protein materials at multiple scales, from nano to macro. We focus on alpha-helix
      based intermediate filament proteins as a model system to explain why the
      utilization of hierarchical structural features is vital to their ability to
      combine strength, robustness, and adaptability. Experimental studies
      demonstrating the activation of angiogenesis, the growth of new blood vessels,
      are presented as an example of how adaptability of structure in biological tissue
      is achieved through changes in gene expression that result in an altered material
      structure. We analyze the concepts in light of the universality and diversity of
      the structural makeup of protein materials and discuss the findings in the
      context of potential fundamental evolutionary principles that control their
      nanoscale structure. We conclude with a discussion of multiscale science in
      biology and de novo materials design.

PMID- 20676306
TI  - Jamal m. Bullocks, m.d.

PMID- 20676307
TI  - Cosmetic surgery in the ethnic population: special considerations and procedures.

PMID- 20676308
TI  - Socioeconomic impact of ethnic cosmetic surgery: trends and potential financial
      impact the african american, asian american, latin american, and middle eastern
      communities have on cosmetic surgery.
AB  - The popularity of cosmetic surgery has increased around the world, and whereas in
      the past, the patient base consisted of mainly Caucasian individuals, interest in
      this field has grown among persons of varying ethnic backgrounds. Growing
      interest enables ethnic populations to contribute to the economic growth of the
      cosmetic surgery industry and impact the direction of the field in the future.
      Minority populations accounted for 22% of the cosmetic procedures performed in
      2007, with the most common being liposuction, Botox((R)) generic botulinum toxin
      type A (Allergan, Inc., Irvine, CA), and chemical peels. Ultimately, changes in
      the population characteristics of the plastic surgery patient will alter the
      techniques of plastic surgeons that treat ethnic patients to cater to their
      physical differences. Factors such as increased cultural acceptance of plastic
      surgery, growing ethnic populations, and media emphasis on personal appearance
      have contributed to the increase in minorities seeking out cosmetic surgery.
      Escalating economic power within these populations has created an additional
      potentially lucrative market for interested plastic surgeons.

PMID- 20676309
TI  - Variations of structural components: specific intercultural differences in facial
      morphology, skin type, and structures.
AB  - Analysis of the differences in facial morphology and skin structure and tone
      among ethnic groups within the realm of plastic surgery is relevant due to the
      increasing number of ethnic individuals seeking cosmetic surgery. Previous
      classifications of ideal facial morphologic characteristics have been revised and
      challenged over the years to accurately reflect the differences in facial
      structure that are aesthetically pleasing to individuals of differing ethnic
      groups. The traditional neoclassic canons reflected the European Caucasian facial
      morphology and cannot be used to classify facial characteristics in ethnic groups
      due to drastic differences in measurement and proportion. In addition,
      differences in biophysiologic properties of ethnic skin types influence the
      progression of aging and the ability of skin to withstand environmental insults.
      Thickness of the stratum corneum, water content, and melanin composition are
      important factors that were analyzed in varying ethnic groups. Although it
      appears that Caucasian Americans are subject to earlier onset of skin wrinkling
      and sagging than are African Americans due to thinner stratum corneum layers and
      decreased water content, more research needs to be conducted to be inclusive of
      other ethnic groups. These data will enable plastic surgeons to treat these
      groups more effectively while preserving their unique characteristics.

PMID- 20676310
TI  - Skin care in ethnic populations.
AB  - Use of over-the-counter cosmetics, approaches to hygiene, and many basic
      dermatologic principles differ between individuals with Caucasian skin and ethnic
      skin. Still, comparatively few publications highlight these variations or discuss
      appropriate management. Among many ethnic patients, issues related to skin
      hydration, restoration of even pigmentation, hair removal, and acne care remain
      problematic yet not fully addressed. As well, there are some dermatologic
      conditions that may be rare in Caucasian skin but are much more common in the
      ethnic patient. Here, we discuss various aspects of skin hydration, dyschromia,
      sunscreen use, and chemical depilatories in the ethnic population.

PMID- 20676311
TI  - Laser therapy in ethnic populations.
AB  - Today, laser therapy is standard treatment for a wide variety of dermatologic
      complaints. From skin rejuvenation to the management of complex vascular
      malformations, laser treatment has proved to be an effective, innovative solution
      to once-challenging dilemmas. However, laser application in those with darker
      complexions remains a topic of great concern. Although contemporary devices may
      use longer-wavelength lasers and cooling devices to isolate target tissues within
      patients with high levels of epidermal melanin, significant risk remains. Today's
      laser surgeon must have a thorough understanding of patient concerns, lesion
      character and response to treatment, as well as the unique needs of those with
      darker skin. In this article, we discuss critical issues in patient assessment,
      proper evaluation of common skin complaints, and laser therapy use for a variety
      of lesions in the ethnic population.

PMID- 20676312
TI  - Keloids: pathogenesis, clinical features, and management.
AB  - Cutaneous wound healing is a complex response to skin injury. Deregulation of
      this process can lead to excessive scar formation, as seen in keloids. Keloids
      are common skin lesions that are difficult to treat and are associated with high
      recurrence rates despite the large number of available treatment options. With
      increased knowledge of the disease process and further scientific advancements,
      future approaches will hopefully improve keloid treatment. In this article, we
      review the epidemiology, genetic basis, etiology, clinical features,
      pathogenesis, and management of keloids.

PMID- 20676313
TI  - Asian blepharoplasty.
AB  - One of the defining features between an individual of Asian descent and someone
      of Western descent is the presence of an upper eyelid crease. Approximately 50%
      of Asians do not have an upper eyelid crease. The double eyelid operation, or
      creation of a supratarsal crease, is the most common cosmetic procedure requested
      in Asia and the third most common procedure requested by Asian Americans. In this
      comprehensive article, we explore the art of creating an eyelid crease in the
      individual who either does not have a crease or has an indistinct crease. We will
      review the history of the development of Asian blepharoplasty, explain the
      anatomy of the Asian eyelid and how it differs from the Caucasian eyelid, and
      clarify how this anatomy then translates to differences in external appearance.
      The two main schools of surgical techniques will be discussed along with pearls,
      pitfalls, and personal observations.

PMID- 20676314
TI  - Rejuvenation of the african american periorbital area: dynamic considerations.
AB  - The rejuvenation of the African American periorbit is rooted in select
      modifications of traditional techniques. The African American patient presents
      with dynamic considerations and needs. Whereas this subset is at risk for
      pigmentation and scar concerns, the natural resistance to actinic damage makes
      rejuvenation efforts rewarding. We will review the composite that makes up the
      periorbit, the brow, upper eyelid, lower eyelid/lateral canthus, and the midface
      unique. Specific indications and presurgical and postsurgical considerations will
      be presented in addition to technical considerations to manage periorbital aging
      that spares the skin. Common pitfalls and succinct ways to avoid them without
      compromising on the ultimate end result will be presented. Ultimately,
      periorbital rejuvenation can be done completely without jeopardizing one's ethnic
      identity.

PMID- 20676315
TI  - Rhinoplasty in the Hispanic patient.
AB  - In the United States, rhinoplasty has traditionally been performed in Caucasian
      patients. Ethnic rhinoplasty is often thought of as a procedure done to reshape
      the nose of a black or Asian patient. Little attention has been paid to
      rhinoplasty in Hispanic patients. There has been a large increase in the Hispanic
      population of the United States, and plastic surgeons will see a concomitant rise
      in requests for rhinoplasty among this population. In an effort to increase our
      understanding of Hispanic rhinoplasty, a retrospective review of a senior
      surgeon's experience was performed. A retrospective chart review was done
      examining the senior author's (S.S.) rhinoplasty practice over the past 10 years.
      Hispanic patients presenting for aesthetic and corrective rhinoplasty (cleft
      patients were excluded) were analyzed. The Hispanic nose was divided into three
      archetypes. Type I is characterized by a high radix and prominent vault; these
      noses should be corrected by dorsal reduction and resection of caudal septum.
      Type II is characterized by a dependent tip with inadequate projection; dorsal
      augmentation with diced cartilage and tip support with cartilage grafts are
      important. Osteotomies should generally be avoided in this group. Type III noses
      are characterized by a broad nasal base with thick skin and a wide tip;
      rhinoplasty in this group requires correction of the dorsum-base disproportion
      using several techniques including columellar struts, tip grafts, and dorsal
      augmentation. Hispanics are projected to become the largest minority population
      within the next 10 years, and rhinoplasty in this population will become more
      frequent over time. It behooves plastic surgeons to become familiar with the
      different archetypes of Hispanic noses and appropriate corrective techniques for
      each.

PMID- 20676316
TI  - Asian rhinoplasty.
AB  - Rhinoplasty for the Asian patient mandates an entirely different strategy than
      for the Occidental nose. The objective for Asian rhinoplasty is augmentation
      rather than reduction in which the dorsum is raised and the nasal tip projection
      and definition are enhanced. The watchword today is ethnic preservation rather
      than effacement for the Asian patient. An ethnically sensitive standard for
      aesthetic rhinoplasty for the Asian nose is proposed. Also, a thorough discussion
      of cultural issues that can be important when working with the Asian patient is
      undertaken to guide a surgeon through every phase of patient care. Finally, the
      technical details are elaborated on both rhinoplasty and revision rhinoplasty for
      the Asian nose with an emphasis on correcting previous silicone augmentation
      rhinoplasty, the most popular choice for material in the Far East but that has
      failed the author in achieving consistent results.

PMID- 20676317
TI  - Rhinoplasty: the african american patient.
AB  - Over the past three decades, an increasing number of African American patients
      have undergone rhinoplasty, and many continue to present to surgeons for
      rhinoplasty evaluation. The reality is that rhinoplasty is no longer an uncommon
      procedure in the African American population. Most patients desire nasal
      refinement while preserving their cultural identity. The African American nose
      has many unique features that have to be appreciated and understood to provide
      the desired outcome. In this paper, we present an overview of the unique anatomic
      features of the African American nose, rhinoplasty techniques tailored to this
      patient population, and complications encountered postoperatively.

PMID- 20676318
TI  - Ethnic considerations in buttock aesthetics.
AB  - There has been increased interest in buttock contouring and augmentation in
      recent years, which has translated into increased demand for these procedures. In
      addition, we are witnessing a growing number of patients from all ethnic groups
      requesting cosmetic surgery in the United States. Buttock aesthetic surgery today
      consists of either augmentation or recontouring of the gluteal region by one of
      three methods: (1) liposuction (if only reductive shaping is required); (2)
      liposuction and augmentation by micro fat grafting; and (3) gluteal implants.
      Whereas there certainly exists a "universal ideal" of beauty in buttock
      augmentation, there are fundamental ethnic differences that must be recognized to
      achieve a desirable surgical outcome. We present an article reviewing current
      trends in buttock aesthetic procedures and discuss issues relevant to the ethnic
      populations.

PMID- 20676319
TI  - Cancer statistics in Korea: incidence, mortality and survival in 2006-2007.
AB  - Cancer has been the leading cause of death in Korea. Korea is facing a very rapid
      change and increase in cancer incidence, which draws much attention in public
      health. This paper overviews the nationwide cancer statistics, including
      incidence, mortality, and survival rates, and their trends in Korea based on the
      cancer incidence data from The Korea Central Cancer Registry (KCCR) in year 2006
      and 2007. In Korea, there were 153,237 cancer cases and 65,519, cancer deaths
      observed in 2006, and 161,920 cancer cases and 67,561 cancer deaths in 2007,
      respectively. The incidence rate for all cancer combined showed an annual
      increase of 2.8% from 1999 to 2007. Specifically, there was significant increase
      in the incidence of colorectal, thyroid, female breast, and prostate cancers. The
      number of cancer deaths has increased over the past two decades, due mostly to
      population aging, while the age-standardized mortality rates have decreased in
      both men and women since 2002. Notable improvement has been observed in the 5-yr
      relative survival rates for most major cancers and for all cancer combined, with
      the exception of pancreatic cancer. The nationwide cancer statistics in this
      paper will provide essential data for cancer research and evidence-based health
      policy in Korea.

PMID- 20676320
TI  - Trends in deceased organ donation and utilization in Korea: 2000-2009.
AB  - Continuous efforts have been made by the organ donation and transplantation
      community in Korea to increase organ donation by the deceased. The authors
      detailed trends of organ donation and utilization over the past 10 yr using data
      provided by the KONOS. The yearly number of deceased donors has grown gradually
      since 2003. The number and percentage of old donors (> or = 50 yr) and donors
      dying from intracranial hemorrhage has increased continuously. Therefore, the
      percentage of standard criteria donors (SCD) has been declining significantly,
      from 94% in 2000 to 79.2% in 2009. The number of organs transplanted per donor
      (OTPD) has also declined slightly since 2007, from 3.28 in 2007 to 2.95 in 2009.
      This decline may be attributable to increases in the number and percentage of
      extended criteria donors (ECD) and donors after cardiac death (DCD), since the
      OTPD was 2.25 for DCD, 2.5 for ECD, and 3.09 for SCD in 2009. In summary, the
      makeup of donors has changed significantly. There is an urgent need for
      establishment of an institutional framework including an independent organ
      procurement organization and for improvement for the National Transplant Act to
      increase deceased donor pool and to optimize management of ECD and DCD.

PMID- 20676321
TI  - Epidemiology of foodborne Norovirus outbreak in Incheon, Korea.
AB  - On June 14, 2008, an outbreak of gastroenteritis occurred among elementary school
      students in Incheon. We conducted an investigation to identify the source and
      described the extent of the outbreak. We performed a retrospective cohort study
      among students, teachers and food handlers exposed to canteen food in the
      elementary school. Using self-administered questionnaires we collected
      information on symptoms, days of canteen food eaten, food items consumed. Stool
      samples were collected from 131 symptomatic people and 11 food handlers. The
      catering kitchen was inspected and food samples were taken. Of the 1,560 people
      who ate canteen food, 117 were symptomatic cases, and the attack rate was 7.5%.
      Consumption of cucumber-crown daisy salad (RR=2.71), fresh cabbage mix (RR=2.23),
      dried radish salad (RR=3.04) and young radish kimchi (RR=2.52) were associated
      with illness. Sixty-four (45%) of the 142 stool specimens were positive for
      Norovirus. Norovirus was detected in 2 food handlers. Interviews with kitchen
      staff indicated the likelihood of contamination from an infected food handler to
      the dried radish salad during food processing. The excretion of Norovirus from
      asymptomatic food handlers may be an infection source of Norovirus outbreaks.

PMID- 20676322
TI  - Customized Asthma Control Test with reflection on sociocultural differences.
AB  - We evaluated the utility and feasibility of customizing Asthma Control Test (ACT)
      items to generate a Korean Asthma Control Test (KACT) specific for Korean
      patients. We surveyed 392 asthma patients with 19 items, selected to reflect the
      Korean sociocultural context. Guideline ratings were integrated with the
      evaluations of specialists (i.e., using both guide base rating together with
      specialist's rating), and items with the greatest discriminating validity were
      identified. Stepwise regression methods were used to select items. KACT scale
      scores showed significant differences between the asthma control ratings
      generated by integrating ratings (r=0.77, P<0.001), by specialist's evaluations
      (r=0.54, P<0.001), or by FEV(1) percent predicted (r=0.39, P<0.001). Specialist's
      and guideline ratings detected 56% and 48.6% of patients with well-controlled
      asthma, respectively. However, the integrated ratings indicated that only 34.3%
      of the patients in the test sample were well controlled. The overall agreement
      between KACT and the integrated rating ranged from 45% to 78%, depending on the
      cut-off points used. It is possible to formulate a valid, useful country-specific
      diagnostic tool for the assessment of asthma patients based on the original ACT
      that reflect differences in sociocultural context.

PMID- 20676323
TI  - Heart rate variability and length of survival in hospice cancer patients.
AB  - We examined the association between heart rate variability (HRV) and survival
      duration to evaluate the usefulness of HRV as a prognostic factor for hospice
      cancer patients. In terminally ill cancer patients who visited the Hospice
      clinic, we checked demographic data, Karnofsky performance scale (KPS), HRV,
      dyspnea, anorexia, as well as fasting blood glucose and total cholesterol. After
      following up their duration of survival, we examined meaningful prognostic
      factors for predicting life expectancy through the survival analysis. A total of
      68 patients were included in final analysis. As KPS was lower, or when combined
      with dyspnea or anorexia, the survival duration was much shorter. HRV parameters
      except heart rate were all impaired in most patients. In particular, the group
      with mean heart rate of 100 or more beats per minute and the group with standard
      deviations of normal-to-normal R-R intervals (SDNN) of 21.3 ms (75 percentile) or
      less showed significantly shorter survival duration. The final multivariate
      analysis adjusting for age, gender, fasting blood glucose, and total cholesterol
      showed that KPS, dyspnea, anorexia, and SDNN were significant prognostic factors
      in survival duration. For the first time, we report that SDNN is a prognostic
      factor in terminal cancer patients.

PMID- 20676324
TI  - Emphysema as a risk factor for the outcome of surgical resection of lung cancer.
AB  - It is unclear whether emphysema, regardless of airflow limitation, is a
      predictive factor associated with survival after lung cancer resection.
      Therefore, we investigated whether emphysema was a risk factor associated with
      the outcome after resection for lung cancer. This study enrolled 237 patients
      with non small cell lung cancer with stage I or II who had surgical removal.
      Patient outcome was analyzed based on emphysema. Emphysema was found in 43.4% of
      all patients. Patients with emphysema were predominantly men and smokers, and had
      a lower body mass index than the patients without emphysema. The patients without
      emphysema (n=133) survived longer (mean 51.2+/-3.0 vs. 40.6+/-3.1 months,
      P=0.042) than those with emphysema (n=104). The univariate analysis showed a
      younger age, higher FEV(1)/FVC, higher body mass index, cancer stage I, and a
      lower emphysema score were significant predictors of better survival. The
      multivariate analysis revealed a younger age, higher body mass index, and cancer
      stage I were independent parameters associated with better survival, however,
      emphysema was not. This study suggests that unfavorable outcomes after surgical
      resection of lung cancer should not be attributed to emphysema itself.

PMID- 20676325
TI  - Identification of novel methylation markers in hepatocellular carcinoma using a
      methylation array.
AB  - Promoter CpG island hypermethylation has become recognized as an important
      mechanism for inactivating tumor suppressor genes or tumor-related genes in human
      cancers of various tissues. Gene inactivation in association with promoter CpG
      island hypermethylation has been reported to be four times more frequent than
      genetic changes in human colorectal cancers. Hepatocellular carcinoma is also one
      of the human cancer types in which aberrant promoter CpG island hypermethylation
      is frequently found. However, the number of genes identified to date as
      hypermethylated for hepatocellular carcinoma (HCC) is fewer than that for
      colorectal cancer or gastric cancer, which can be attributed to fewer attempts to
      perform genome-wide methylation profiling for HCC. In the present study, we used
      bead-array technology and coupled methylation-specific PCR to identify new genes
      showing cancer-specific methylation in HCC. Twenty-four new genes have been
      identified as hypermethylated at their promoter CpG island loci in a cancer
      specific manner. Of these, TNFRSF10C, HOXA9, NPY, and IRF5 were frequently
      hypermethylated in hepatocellular carcinoma tissue samples and their methylation
      was found to be closely associated with inactivation of gene expression. Further
      study will be required to elucidate the clinicopathological implications of these
      newly found DNA methylation markers in hepatocellular carcinoma.

PMID- 20676326
TI  - Efficacy of high-dose chemotherapy and autologous stem cell transplantation in
      patients with relapsed medulloblastoma: a report on the Korean Society for
      Pediatric Neuro-Oncology (KSPNO)-S-053 study.
AB  - The efficacy and toxicity of high-dose chemotherapy and autologous stem cell
      transplantation (HDCT/ASCT) were investigated for improving the outcomes of
      patients with relapsed medulloblastoma. A total of 15 patients with relapsed
      medulloblastoma were enrolled in the KSPNO-S-053 study from May 2005 to May 2007.
      All patients received approximately 4 cycles of salvage chemotherapy after
      relapse. Thirteen underwent HDCT/ASCT; CTE and CM regimen were employed for the
      first HDCT (HDCT1) and second HDCT (HDCT2), respectively, and 7 underwent HDCT2.
      One transplant related mortality (TRM) due to veno-occlusive disease (VOD)
      occurred during HDCT1 but HDCT2 was tolerable with no further TRM. The 3-yr
      overall survival probability and event-free survival rates +/-95% confidence
      intervals (CI) were 33.3+/-12.2% and 26.7% +/-11.4%, respectively. When analysis
      was confined to only patients who had a complete response (CR) or partial
      response (PR) prior to HDCT, the probability of 3-yr overall survival rates +/
      95% CI was 40.0+/-15.5%. No patients with stable disease (SD) or progressive
      disease (PD) survived. Survival rates from protocol KSPNO-S-053 are encouraging
      and show that tumor status prior to HDCT/ASCT is an important factor to consider
      for improving survival rates of patients with relapsed medulloblastoma.

PMID- 20676327
TI  - Prevalence of asymptomatic critical carotid artery stenosis in Korean patients
      with chronic atherosclerotic lower extremity ischemia: is a screening carotid
      duplex ultrasonography worthwhile?
AB  - This study aimed to investigate prevalence of asymptomatic carotid artery
      stenosis (ACAS) in Korean patients with peripheral arterial disease (PAD) and
      identify predictive factors of ACAS in patients with PAD. Between 1994 and 2008,
      546 patients who underwent bypass surgery due to PAD were identified in a single
      tertiary teaching hospital. Of those, 409 patients underwent preoperative
      screening carotid duplex ultrasonography (CDUS). Patients who had an episode of
      cerebrovascular event or previous carotid artery intervention were excluded and
      then a retrospective analysis was made of 340 patients. The degree of internal
      carotid artery (ICA) stenosis was determined by the criteria of Society of
      Radiologists in Ultrasound Consensus Conference. To determine the risk factors of
      ACAS, demographic, coexisting medical condition and lesion characteristics were
      tested with binary logistic regression model. The prevalence of > or = 70% ICA
      stenosis was 14%. ICA occlusion was detected in 7.1%. Multivariate analysis
      revealed age > 65 yr (OR: 2.610, 95% CI: 1.197-5.691) and coronary artery disease
      (CAD, OR: 2.333, 95% CI: 1.169-4.657) are predictive factors of > or = 70%
      stenosis. A PAD patient who needs revascularization, particularly, > 65 yr or has
      a concomitant CAD, can be a good candidate of screening CDUS.

PMID- 20676328
TI  - Correlation of undercarboxylated osteocalcin (ucOC) concentration and bone
      density with age in healthy Korean women.
AB  - Uncarboxylated osteocalcin (ucOC) is important in evaluating vitamin K status and
      it is inversely associated with bone mineral density (BMD). We studied the
      correlationship between ucOC and BMD in healthy Korean women. This study
      recruited 337 healthy women between ages 20-70 were recruited. Serum ucOC,
      calcium, alkaline phosphatase, body mass index (BMI), and BMD were measured and
      compared. Mean BMI was lowest (20.3+/-1.9 kg/m(2)) in the 20 yr old group and
      highest (24.8+/-2.6 kg/m(2)) in the 60 yr old group. Women age 20-70 yr old had
      ucOC inversely related to BMD independent of other factors that may influence
      BMD. Serum ucOC concentration and BMD of lumbar spine showed a significant
      inverse relationship. Serum mean alkaline phosphatase was lowest (122+/-30 IU/L)
      in the age 30 group and highest (190.3+/-55.8 IU/L) in the age 60 group. Serum
      ucOC was inversely associated with BMI, and positively associated with alkaline
      phosphatase. Uncarboxylated osteocalcin (ucOC) was inversely associated with
      spinal BMD in healthy Korean women. Serum mean ucOC was highest in the age 20
      group, followed by age 50 group, which may indicate vitamin K insufficiency could
      be related to high bone turnover in these groups. These results suggest that
      vitamin K supplement may be considered to help both bone growth and bone loss
      during these periods.

PMID- 20676329
TI  - Subclinical hypothyroidism has little influences on muscle mass or strength in
      elderly people.
AB  - Sarcopenia, the age-related decline in muscle mass, affects the muscle strength
      and muscle quality, and these changes decrease functional capacity. The
      prevalence of thyroid dysfunction increases with age, and changes in thyroid
      hormone level lead to neuromuscular deficits. We investigated the effects of
      subclinical hypothyroidism on the muscle mass, strength or quality in elderly
      people. One thousand one hundred eighteen subjects aged > or = 65 yr were
      randomly selected from a local population and classified into a euthyroid (280
      men and 358 women), subclinically hypothyroid (61 men and 75 women), or overtly
      hypothyroid (7 men and 16 women) group. Although women with subclinical
      hypothyroidism had a higher prevalence of sarcopenia, defined according to the
      ratio of appendicular skeletal muscle mass to the square of height, muscle mass,
      strength or quality did not differ in relation to thyroid status in men or in
      women. Multivariate analysis including age, diabetes, hypertension, acute
      coronary event, alcohol, smoking, presence of pain, physical activity score, and
      lipid profile, showed that thyroid-stimulating hormone level was not associated
      with muscle mass, strength or quality. In conclusion, subclinical hypothyroidism
      has little influences on muscle mass, strength or quality, and may not be
      associated with sarcopenia.

PMID- 20676330
TI  - A nationwide survey of lymphangioleiomyomatosis in Korea: recent increase in
      newly diagnosed patients.
AB  - In 2007, the Korean Interstitial Lung Disease Society had collected clinical data
      of patients who have diagnosed as Lymphangioleiomyomatosis (LAM) since 1990
      through nationwide survey, which showed that LAM patients had increased sharply
      after 2004. The present study was performed to show the clinical features of
      Korean patients with LAM, and to establish the reason for the recent increase in
      the diagnosis. All 63 patients were women and the mean age at diagnosis was 36
      yr. The most common presenting symptom was dyspnea and 8 patients had tuberous
      sclerosis complex. The survival rate at 5 yr after diagnosis was 84%. Compared
      with patients diagnosed after 2004 (n=34), the patients diagnosed before 2004
      (n=29) complained with dyspnea more (P=0.016) and had lower FEV(1)% predicted
      (P=0.003), and DLco% predicted (P=0.042). The higher proportion of patients
      diagnosed after 2004 showed the normal chest radiography, and they were detected
      by routine chest CT screening (P=0.016). This study showed that clinical features
      of Korean patients with LAM were not different from those reported elsewhere. It
      is concluded that the reason for the increase of newly diagnosed patients is the
      result of increase in detection of the early stage LAM by the widespread use of
      chest CT screening.

PMID- 20676331
TI  - Effects of body composition, leptin, and adiponectin on bone mineral density in
      prepubertal girls.
AB  - Body weight is positively associated with bone mineral density but the
      relationship between obesity and bone mineral density is unclear. Leptin and
      adiponectin are potential independent contributors to bone mineral density. We
      assessed the correlations of body composition, leptin and adiponectin with bone
      mineral density, and whether leptin, adiponectin and body composition determine
      bone mineral density independently in prepubertal girls. Forty-eight prepubertal
      girls were classified into obese and control groups by body mass index. Serum
      leptin and adiponectin levels were determined by enzyme immunoassay. Bone mineral
      density was measured using dual energy radiography absorptiometry and body
      composition was measured using bioelectrical impedance analysis. Lean and fat
      mass, and leptin were positively correlated with bone mineral density. Lean mass
      was a positive independent predictor of femoral and L-spine bone mineral density.
      Serum leptin was a positive independent predictor of femoral bone mineral
      density. Fat mass was a negative independent predictor of femoral bone mineral
      density. In prepubertal girls, lean mass has a favorable effect on bone mineral
      density. Fat mass seems not to protect the bone structure against osteoporosis,
      despite increased mechanical loading. Serum leptin may play a biological role in
      regulating bone metabolism.

PMID- 20676332
TI  - Recent trends in the incidence of multiple births and its consequences on
      perinatal problems in Korea.
AB  - The aim of this study was to survey multiple birth data and to analyze the recent
      trends of multiple births and its consequences on perinatal problems in Korea
      from 1991 to 2008. Data were obtained from the Korean Statistical Information
      Service. The total number of multiple births showed increasing trends. The
      multiple birth rate was maintained within less than 10.0 for the decade from 1981
      to 1990. However, it increased gradually to reach 27.5 in 2008. The maternal age
      for multiple births was higher than for total live births. The mean birth weight
      of the total live births was 3.23 kg; for the multiple births it was 2.40 kg in
      2008. The incidence of low birth weight infants (LBWI) among total live births
      was 3.8% in 2000 and 4.9% in 2008. For multiple births it was 49.2% and 53.0%
      during the same years. The incidence of preterm births among total live births
      was 3.8% in 2000 and 5.5% in 2008; for the multiple births it was 38.3% and 51.5%
      during the same years. The incidence of multiple births and its consequences on
      perinatal problems (preterm, LBWI, and advanced-maternal age) have been increased
      steadily over the last two decades in Korea.

PMID- 20676333
TI  - Vaccination with a human papillomavirus (HPV)-16/18 AS04-adjuvanted cervical
      cancer vaccine in Korean girls aged 10-14 years.
AB  - The human papillomavirus (HPV)-16/18 AS04-adjuvanted cervical cancer vaccine has
      been demonstrated to be highly efficacious and immunogenic with a favorable
      safety profile. This study assessed the immunogenicity and safety of the HPV
      16/18 AS04-adjuvanted vaccine in healthy Korean girls aged 10-14 yr. This multi
      center, observer-blind trial randomly assigned 321 healthy girls to receive three
      doses (0, 1, 6-month schedule) of HPV-16/18 AS04-adjuvanted vaccine or hepatitis
      A vaccine. Immunogenicity against vaccine antigens was assessed one month post
      Dose 3. Solicited and unsolicited adverse events (AEs) and serious AEs (SAEs)
      were recorded. In the according-to-protocol analysis, all initially seronegative
      subjects vaccinated with the HPV-16/18 AS04-adjuvanted vaccine had seroconverted
      at Month 7, with a peak geometric mean titer (GMT) that was 600-fold higher than
      the natural infection titer of 29.8 EU/mL for HPV-16 and a peak GMT that was 400
      fold higher than the natural infection titer of 22.6 EU/mL for HPV-18. The
      vaccine was well tolerated with no increase in reactogenicity with subsequent
      doses and no reports of vaccine-related SAEs. In conclusion, the HPV-16/18 AS04
      adjuvanted vaccine is shown to be highly immunogenic and generally well-tolerated
      in Korean girls aged 10-14 yr.

PMID- 20676334
TI  - Risk factors for antimicrobial resistance among the Escherichia coli strains
      isolated from Korean patients with acute uncomplicated cystitis: a prospective
      and nationwide study.
AB  - We investigated the risk factors for resistance to ciprofloxacin, cefazolin,
      ampicillin and co-trimoxazole in Escherichia coli isolates from urine of Korean
      female patients with acute uncomplicated cystitis (AUC). A total of 225 patients
      and their E. coli isolates were prospectively and nationwidely enrolled between
      May and October, 2006. All the antimicrobials did not show any differences
      according to the age group. A higher rate of ciprofloxacin resistance was
      observed in the south (OR: 3.04, 95% CI: 1.19-7.80 for Chungcheong-do & Jeolla
      do; OR: 3.04, 95% CI: 1.22-7.58 for Gyeongsang-do) compared to Gyeonggi-do. Two
      recurrences of AUC in the past year was an important risk factor for
      antimicrobial resistance (ciprofloxacin; OR: 6.71, 95% CI: 1.86-24.11 and
      cefazolin; OR: 5.72, 95% CI: 1.20-27.25). However, the resistance to co
      trimoxazole and ampicillin was not associated with any of the risk factors. This
      study also revealed the pattern of multi-drugs resistance in ciprofloxacin
      resistant E. coli strains. In conclusion, for Korean patients with two more
      recurrences of AUC in the past year, it is strongly recommended to perform an
      antimicrobial sensitivity test with a urine sample before empirical treatment.

PMID- 20676335
TI  - Reliability and validity of the Korean version of the Penn State Worry
      Questionnaire in primary school children.
AB  - Worry is a generalized psychological phenomenon seen among most people. When
      worry is excessive and nearly uncontrollable, people usually suffer psychological
      pain. The Penn State Worry Questionnaire for Children (PSWQ-C) was developed to
      measure worry objectively. It comprises 14 items for measuring excessive,
      generalized, and uncontrollable worry in children. This study, conducted with a
      large group of elementary children (3rd through 6th graders, ages 8-12 yr;
      N=973), investigated the reliability and validity of the Korean version of the
      Penn State Worry Questionnaire for Children (PSWQ-CK). The PSWQ-CK showed high
      reliability by test-retest and also excellent internal consistency results. To
      examine the validity of the PSWQ-CK, we calculated its correlation with the
      Revised Children's Manifest Anxiety Scale (RCMAS). The PSWQ-CK had a higher
      correlation with the worry/oversensitivity factor than with other subscales of
      the RCMAS, and it showed no correlation with the lie factor. When 3 reversed PSWQ
      CK items were eliminated, the instrument showed higher internal consistency.
      However, this did not improve its correlation with other anxiety-measuring tools.
      In conclusion, the PSWQ-CK's reliability and validity were satisfactory, and it
      is a useful tool for objectively measuring the worry of Korean children of this
      age group.

PMID- 20676336
TI  - Characteristics of 681 low vision patients in Korea.
AB  - The purpose of our study was to evaluate the characteristics and the changes of
      low vision patients over ten years in Korea, and to establish useful data for
      planning low vision services, active care and rehabilitation. We conducted a
      retrospective study of 681 low vision patients who visited two low vision clinics
      in Seoul from 1995 to 2008. Age and sex distribution, cause of low vision, type
      of prescribed low vision aids, and changes of the characteristics were reviewed.
      In result, male were more than female. The age group between 11 and 20-yr-old
      (18.1%) was the largest age group. Optic atrophy (28.3%) was main causes of low
      vision. However, elderly low vision patients is increasing and macular
      degeneration is becoming a leading cause of low vision (P<0.05). One thousand
      five low vision aids (LVAs) were prescribed for 681 patients (1.46+/-0.62 aids
      for each patient). Near LVAs were prescribed more than distance LVAs. In most
      patients, the use of LVAs improved both near and distance visual function. This
      study is the first survey of a large number of low vision patients over a ten
      year period in Korea. On the base of this study, the planning of low vision
      services and more active rehabilitation for low vision patients, especially
      elderly patients, need in Korea.

PMID- 20676337
TI  - Propofol and aminophylline antagonize each other during the mobilization of
      intracellular calcium in human umbilical vein endothelial cells.
AB  - This study examined whether propofol and aminophylline affect the mobilization of
      intracellular calcium in human umbilical vein endothelial cells. Intracellular
      calcium was measured using laser scanning confocal microscopy. Cultured and serum
      starved cells on round coverslips were incubated with propofol or aminophylline
      for 30 min, and then stimulated with lysophosphatidic acid, propofol and
      aminophylline. The results were expressed as relative fluorescence intensity and
      fold stimulation. Propofol decreased the concentration of intracellular calcium,
      whereas aminophylline caused increased mobilization of intracellular calcium in a
      concentration-dependent manner. Propofol suppressed the lysophosphatidic acid
      induced mobilization of intracellular calcium in a concentration-dependent
      manner. Propofol further prevented the aminophylline-induced increase of
      intracellular calcium at clinically relevant concentrations. However,
      aminophylline reversed the inhibitory effect of propofol on the elevation of
      intracellular calcium by lysophosphatidic acid. Our results suggest that propofol
      and aminophylline antagonize each other on the mobilization of intracellular
      calcium in human umbilical vein endothelial cells at clinically relevant
      concentrations. Serious consideration should be given to how this interaction
      affects mobilization of intracellular calcium when these two drugs are used
      together.

PMID- 20676338
TI  - Double facial nerve trunk emerged from the stylomastoid foramen and petrotympanic
      fissure: a case report.
AB  - There are several studies concerning branches of the facial nerve, but we
      encountered less information about the trunk of the facial nerve in the
      literature. During the routine dissection of a 65-yr-old Caucasian male cadaver,
      double facial nerve trunk emerged from the stylomastoid foramen and petrotympanic
      fissure were encountered. Because of an extremely rare variation, we presented
      this case report. In addition this cadaver had two buccal plexuses. These
      plexuses and other branches were formed to structures like to polygon. These
      anatomic peculiarities were described, photographed and illustrated. Finally,
      magnetic resonance imaging was performed by using 1.5T scanner to this cadaver.
      The facial nerve trunk can be damaged during surgical procedures of the parotid
      gland tumours and submandibular region. Surgeons who are willing to operate on
      this area should be aware of the possible anatomical variations of the facial
      nerve trunk.

PMID- 20676339
TI  - A case of anaphylaxis to oral minocycline.
AB  - Minocycline is a semisynthetic tetracycline derivative that is often used in the
      treatment of acne vulgaris. To date, there has been only one case report of
      anaphylaxis to minocycline. We report here a case of anaphylaxis to oral
      minocycline. A 56-yr-old woman visited our hospital after three episodes of
      recurrent anaphylaxis. We performed an oral challenge test, the standard method
      for diagnosing drug allergies, with minocycline, one of the drugs she had taken
      previously. She developed urticaria, angioedema, nausea, vomiting, hypotension,
      and dyspnea within 4 min and was treated with intramuscular epinephrine,
      intravenous antihistamine and systemic corticosteroid. However, she presented
      similar symptoms at 50 min and at 110 min. In prescribing oral minocycline,
      physicians should consider the possibility of serious adverse reactions, such as
      anaphylaxis.

PMID- 20676340
TI  - Erysipelothrix rhusiopathiae peritonitis in a patient undergoing continuous
      ambulatory peritoneal dialysis.
AB  - Erysipelothrix rhusiopathiae is known as a pathogen of occupational diseases or a
      zoonosis. We report a case of E. rhusiopathiae peritonitis in a 50-yr-old male
      undergoing continuous ambulatory peritoneal dialysis (CAPD). He was suffered from
      mild abdominal pain with a distinctive erysipeloid skin lesion. E. rhusiopathiae
      was considered to be introduced through a lacerated wound on his hand when he was
      exposed to contaminated materials. He was treated successfully with a first
      generation cephalosporin. To our knowledge, CAPD peritonitis due to E.
      rhusiopathiae is very rare, and this is a report of the first case in Asia.

PMID- 20676341
TI  - A case of congenital central hypoventilation syndrome with PHOX2B gene mutation
      in a Korean neonate.
AB  - Congenital central hypoventilation syndrome (CCHS) is a life-threatening disorder
      with apnea and cyanosis during sleep requiring immediate endotracheal intubation
      during the first day of life. The PHOX2B gene has been identified as the major
      gene involved in CCHS. This is the first report of a Korean neonate with CCHS
      confirmed to have a PHOX2B mutation with expanded alleles containing 20
      polyalanine repeats that is a relatively small number compared to previous cases.
      The patient required intermittent ventilator support during sleep only and did
      not suffer from any other disorders of the autonomic nerve system. He
      consistently needs ventilator support during sleep and remains alive. Analysis of
      PHOX2B gene is useful for diagnosis and appropriate therapeutic intervention of
      CCHS patients.

PMID- 20676342
TI  - Successful vaginal delivery of a pregnant woman with Cantrell's Pentalogy.
AB  - Cantrell's Pentalogy is a rare condition that consists of defects involving the
      abdominal wall, lower sternum, anterior diaphragm, pericardium, and heart. In the
      literature to date, pregnant women with Cantrell's Pentalogy have not been
      discussed. We performed successful vaginal delivery of a 23-yr-old nulliparous,
      primigravid woman who had been diagnosed with this condition. Diagnosis was based
      on cardiac catheterization, angiography, and echocardiogram, and abdominopelvic
      CT. Vaginal delivery may be an option for women with Cantrell's Pentalogy and may
      be attempted with caution.

PMID- 20676343
TI  - Reversible splenium lesion of the corpus callosum in hemorrhagic fever with renal
      failure syndrome.
AB  - This is the first case of virus-associated encephalitis/encephalopathy in which
      the pathogen was Hantaan virus. A 53-yr-old man presented fever, renal failure
      and a hemorrhagic tendency and he was diagnosed with hemorrhagic fever with renal
      failure syndrome (HFRS). In the course of his illness, mild neurologic symptoms
      such as dizziness and confusion developed and magnetic resonance images revealed
      a reversible lesion in the splenium of the corpus callosum. This case suggests
      that HFRS patients with neurologic symptoms like dizziness and mental slowing
      should be considered to have structural brain lesions and to require brain
      imaging studies.

PMID- 20676344
TI  - Traumatic cervical cord transection without facet dislocations--a proposal of
      combined hyperflexion-hyperextension mechanism: a case report.
AB  - A patient is presented with a cervical spinal cord transection which occurred
      after a motor vehicle accident in which the air bag deployed and the seat belt
      was not in use. The patient had complete quadriplegia below the C5 level and his
      imaging study showed cervical cord transection at the level of the C5/6 disc
      space with C5, C6 vertebral bodies and laminar fractures. He underwent a C5
      laminectomy and a C4-7 posterior fusion with lateral mass screw fixation.
      Previous reports have described central cord syndromes occurring in
      hyperextension injuries, but in adults, acute spinal cord transections have only
      developed after fracture-dislocations of the spine. A case involving a post
      traumatic spinal cord transection without any evidence of radiologic facet
      dislocations is reported. Also, we propose a combined hyperflexion-hyperextension
      mechanism to explain this type of injury.

PMID- 20676345
TI  - Corneal perforation with preseptal cellulitis in a patient with acute lymphocytic
      leukemia.
AB  - We report a case of corneal perforation with preseptal cellulitis in a patient
      with acute lymphocytic leukemia (ALL). A 17-yr-old female patient who was
      undergoing combination chemotherapy for ALL was referred due to upper lid
      swelling and pain in the right eye for 2 days. Visual acuity in the right eye was
      20/20. Initial examination showed no abnormal findings, other than swelling of
      the right upper eyelid. Computed tomography showed a finding of preseptal
      cellulitis. Microbiologic study of bloody and purulent discharge revealed
      Serratia marcescens. Corneal melting and perforation with iris prolapse were
      detected in the right eye on the 16th day. Emergent tectonic keratoplasty was
      performed. Seven months after surgery, visual acuity in the right eye was 20/300,
      and the corneal graft was stable.

PMID- 20676346
TI  - Endobronchial stent insertion to manage hemoptysis caused by lung cancer.
AB  - Hemoptysis in patients with lung cancer is not uncommon and sometimes have
      dangerous consequences. Hemoptysis has been managed with various treatment
      options other than surgery and medicine, such as endobronchial tamponade,
      transcatheter arterial embolization and radiation therapy. However, these methods
      can sometimes be used only temporarily or are not suitable for a patient's
      condition. We present a case in which uncontrollable hemoptysis caused by central
      lung cancer was successfully treated by inserting a covered self-expanding
      bronchial stent. The patient could be extubated and was able to undergo further
      palliative therapy. No recurrent episodes of hemoptysis occurred for the
      following three months. As our case, airway stenting is a considerable option for
      the tamponade of a bleeding lesion that cannot be successfully managed with other
      treatment methods and could be used to preserve airway patency in a select group
      of patients.

PMID- 20676347
TI  - Metabolic super scan in F-FDG PET/CT imaging.
AB  - A 50-yr-old man presented with intermittent hemoptysis and was diagnosed small
      cell lung cancer. (18)F-FDG PET/CT for staging demonstrated extensive
      hypermetabolic lesions throughout the skeleton and liver. Interestingly, skeletal
      muscles of limbs, mediastinum, bowel, and especially brain showed very low FDG
      uptake. Because of some characteristics in common with super scan on skeletal
      scintigraphy, this case could be considered as 'metabolic super scan'.

PMID- 20676350
TI  - Socioeconomic Status, Family Processes, and Individual Development.
AB  - Research during the past decade shows that social class or socioeconomic status
      (SES) is related to satisfaction and stability in romantic unions, the quality of
      parent-child relationships, and a range of developmental outcomes for adults and
      children. This review focuses on evidence regarding potential mechanisms proposed
      to account for these associations. Research findings reported during the past
      decade demonstrate support for an interactionist model of the relationship
      between SES and family life, which incorporates assumptions from both the social
      causation and social selection perspectives. The review concludes with
      recommendations for future research on SES, family processes and individual
      development in terms of important theoretical and methodological issues yet to be
      addressed.

PMID- 20676351
TI  - Teachers' Perceptions of Word Callers and Related Literacy Concepts.
AB  - The purpose of the study was to investigate teachers' perceptions of word callers
      as they relate to the concepts of reading fluency and reading comprehension. To
      this end, second grade students (N = 408) completed a series of reading fluency
      and reading comprehension assessments, and their teachers (N = 31) completed word
      caller nominations and a questionnaire regarding their concepts surrounding these
      issues. Our findings suggested that teachers often over nominated children as
      word callers. Further, questionnaire data indicated a great deal of ambiguity and
      inconsistency exists regarding teachers' understanding and use of the term word
      caller. By contrast, teachers seemed to possess a veridical understanding of the
      related terms reading fluency and reading comprehension.

PMID- 20676352
TI  - Negotiating the Relationship Between Addiction, Ethics, and Brain Science.
AB  - Advances in neuroscience are changing how mental health issues such as addiction
      are understood and addressed as a brain disease. Although a brain disease model
      legitimizes addiction as a medical condition, it promotes neuro-essentialist
      thinking, categorical ideas of responsibility and free choice, and undermines the
      complexity involved in its emergence. We propose a 'biopsychosocial systems'
      model where psycho-social factors complement and interact with neurogenetics. A
      systems approach addresses the complexity of addiction and approaches free choice
      and moral responsibility within the biological, lived experience and socio
      historical context of the individual. We examine heroin-assisted treatment as an
      applied case example within our framework. We conclude with a discussion of the
      model and its implications for drug policy, research, addiction health care
      systems and delivery, and treatment of substance use problems.

PMID- 20676353
TI  - The Application of Behavior Change Theory to Family-Based Services: Improving
      Parent Empowerment in Children's Mental Health.
AB  - We describe the development of a parent empowerment program (PEP) using a
      community-based participatory research approach. In collaboration with a group of
      dedicated family advocates working with the Mental Health Association of New York
      City and state policy makers, academic researchers took an iterative approach to
      crafting and refining PEP to better prepare family advocates to help bridge the
      gaps in service access among children with emotional and behavioral problems.
      Despite the growth of family-led, family support programs nationally, research
      that demonstrates the positive benefits of such programs is scarce in the
      children's mental health literature. The PEP model is based on research data
      about barriers families face in mental health service utilization (e.g., stigma,
      perceptions of providers, attitudes towards mental illness, service availability,
      etc.). PEP is premised on (a) the concept of empowerment as a process, (b) the
      need to engage parents in becoming active agents of change, and (c) the
      application of an integrated framework to empower parents, called the Parents as
      Agents of Change model. Our paper focuses on describing the application of a
      Unified Theory of Behavior Change as a theoretical framework to help activate
      parents as change agents in meeting their children's mental health needs. Based
      on an integrated model of grassroots driven Principles of Parent Support and
      research-based Unified Theory of Behavior Change, PEP's Parents as Agents of
      Change model provides a conceptual framework for testing the effectiveness of
      family support services in children's mental health, a much-needed area for
      future research.

PMID- 20676354
TI  - Regularization Parameter Selections via Generalized Information Criterion.
AB  - We apply the nonconcave penalized likelihood approach to obtain variable
      selections as well as shrinkage estimators. This approach relies heavily on the
      choice of regularization parameter, which controls the model complexity. In this
      paper, we propose employing the generalized information criterion (GIC),
      encompassing the commonly used Akaike information criterion (AIC) and Bayesian
      information criterion (BIC), for selecting the regularization parameter. Our
      proposal makes a connection between the classical variable selection criteria and
      the regularization parameter selections for the nonconcave penalized likelihood
      approaches. We show that the BIC-type selector enables identification of the true
      model consistently, and the resulting estimator possesses the oracle property in
      the terminology of Fan and Li (2001). In contrast, however, the AIC-type selector
      tends to overfit with positive probability. We further show that the AIC-type
      selector is asymptotically loss efficient, while the BIC-type selector is not.
      Our simulation results confirm these theoretical findings, and an empirical
      example is presented. Some technical proofs are given in the online supplementary
      material.

PMID- 20676355
TI  - Collateral Consequences of Violence in Disadvantaged Neighborhoods.
AB  - Using data from Addhealth, this study investigates the role of neighborhood
      violence in mediating the effects of neighborhood disadvantage on high school
      graduation and teenage pregnancy. Results show that neighborhood violence is a
      strong predictor of both outcomes, net of individual, family, community, and
      school controls. Neighborhood violence accounts for almost half the conditional
      association between neighborhood disadvantage and high school graduation among
      males and almost all of the association among females. Violence also accounts for
      about one fifth of the conditional association between disadvantage and teenage
      pregnancy among adolescents of both genders. Violence is a critical social
      characteristic of disadvantaged neighborhoods, one that explains a sizable
      portion of the effects of growing up in such neighborhoods.

PMID- 20676356
TI  - An invasive whitefly feeding on a virus-infected plant increased its egg
      production and realized fecundity.
AB  - BACKGROUND: Plant-pathogenic begomoviruses have a complex association with their
      insect vectors. The interactions of begomoviruses and reproduction of their
      vectors are poorly understood. Bemisia tabaci is known to transmit many
      begomoviruses, and the spread of B. tabaci, especially the B and Q 'biotypes',
      has been accompanied by the epidemics of begomoviruses. One of these identified
      disease-causing agents was Tomato yellow leaf curl China virus (TYLCCNV).
      METHODOLOGY/PRINCIPAL FINDINGS: In this study, we compared the egg production and
      realized fecundity of two 'biotypes' or putative species of the whitefly B.
      tabaci, including the alien invasive B and the indigenous ZHJ1 from Zhejiang,
      China, feeding on either healthy or TYLCCNV-infected tobacco plants. The ovary of
      the whitefly was composed of 12-22 telotrophic ovarioles. According to the
      morphology of the oocytes and level of yolk content, oocytes in ovarioles were
      divided into four developmental phases (I-IV). Significantly higher proportion of
      immature oocytes (phase II, III) and mature oocytes (phase IV) was observed in
      ovary of females that fed on TYLCCNV-infected tobacco compared to that on healthy
      plants. Moreover, there was significant increase of eggs laid of B whitefly that
      fed on TYLCCNV-infected tobacco plants during the early developmental stages. In
      contrast, the proportion of oocytes of different developmental phases and eggs
      laid had no significant differences between ZHJ1 whiteflies feeding on TYLCCNV
      infected and non-infected host plants. CONCLUSIONS/SIGNIFICANCE: The invasive B
      whitefly benefits from feeding on a begomovirus-infected plant through increased
      egg production and realized fecundity.

PMID- 20676358
TI  - Making journals accessible to the visually impaired: the future is near.
AB  - The American Physical Society (APS) has been a leader in using markup languages
      for publishing. ViewPlus has led development of innovative technologies for
      graphical information accessibility by people with print disabilities. APS,
      ViewPlus, and other collaborators in the Enhanced Reading Project are working
      together to develop the necessary technology and infrastructure for APS to
      publish its journals in the DAISY (Digital Accessible Information SYstem)
      eXtended Markup Language (XML) format, in which all text, math, and figures would
      be accessible to people who are blind or have other print disabilities. The first
      APS DAISY XML publications are targeted for late 2010.

PMID- 20676357
TI  - Structural and biochemical characterization of the human cyclophilin family of
      peptidyl-prolyl isomerases.
AB  - Peptidyl-prolyl isomerases catalyze the conversion between cis and trans isomers
      of proline. The cyclophilin family of peptidyl-prolyl isomerases is well known
      for being the target of the immunosuppressive drug cyclosporin, used to combat
      organ transplant rejection. There is great interest in both the substrate
      specificity of these enzymes and the design of isoform-selective ligands for
      them. However, the dearth of available data for individual family members
      inhibits attempts to design drug specificity; additionally, in order to define
      physiological functions for the cyclophilins, definitive isoform characterization
      is required. In the current study, enzymatic activity was assayed for 15 of the
      17 human cyclophilin isomerase domains, and binding to the cyclosporin scaffold
      was tested. In order to rationalize the observed isoform diversity, the high
      resolution crystallographic structures of seven cyclophilin domains were
      determined. These models, combined with seven previously solved cyclophilin
      isoforms, provide the basis for a family-wide structure:function analysis.
      Detailed structural analysis of the human cyclophilin isomerase explains why
      cyclophilin activity against short peptides is correlated with an ability to
      ligate cyclosporin and why certain isoforms are not competent for either
      activity. In addition, we find that regions of the isomerase domain outside the
      proline-binding surface impart isoform specificity for both in vivo substrates
      and drug design. We hypothesize that there is a well-defined molecular surface
      corresponding to the substrate-binding S2 position that is a site of diversity in
      the cyclophilin family. Computational simulations of substrate binding in this
      region support our observations. Our data indicate that unique isoform
      determinants exist that may be exploited for development of selective ligands and
      suggest that the currently available small-molecule and peptide-based ligands for
      this class of enzyme are insufficient for isoform specificity.

PMID- 20676359
TI  - Disulfide-Depleted Selenoconopeptides: a Minimalist Strategy to Oxidative Folding
      of Cysteine-Rich Peptides.
AB  - Despite the therapeutic promise of disulfide-rich, peptidic natural products,
      their discovery and structure/function studies have been hampered by inefficient
      oxidative folding methods for their synthesis. Here we report that converting the
      three disulfide-bridged mu-conopeptide KIIIA into a disulfide-depleted
      selenoconopeptide (by removal of a noncritical disulfide bridge and substitution
      of a disulfide- with a diselenide-bridge) dramatically simplified its oxidative
      folding while preserving the peptide's ability to block voltage-gated sodium
      channels. The simplicity of synthesizing disulfide-depleted selenopeptide analogs
      containing a single disulfide bridge allowed rapid positional scanning at Lys7 of
      mu-KIIIA, resulting in the identification of K7L as a mutation that improved the
      peptide's selectivity in blocking a neuronal (Na(v)1.2) over a muscle (Na(v)1.4)
      subtype of sodium channel. The disulfide-depleted selenopeptide strategy offers
      regioselective folding compatible with high throughput chemical synthesis and on
      resin oxidation methods, and thus shows great promise to accelerate the use of
      disulfide-rich peptides as research tools and drugs.

PMID- 20676361
TI  - Synthesis and Evaluation of Haloacetyl, alpha-Bromoacryloyl and Nitrooxyacetyl
      Benzo[b]furan and Benzo[b]thiophene Derivatives as Potent Antiproliferative
      Agents Against Leukemia L1210 and K562 Cells.
AB  - Identification of novel and selective anticancer agents remains an important and
      challenging goal in pharmacological research. In search of new compounds with
      strong antiproliferative activity and simple molecular structure, we have
      synthesized three different series of compounds in which different substituents
      were linked to the 3-amino position of the 2-(3', 4', 5'-trimethoxybenzoyl)
      benzo[b]furan or benzo[b]thiophene ring system. These substituents, corresponding
      to acetyl/haloacetyl, alpha-bromoacryloyl and nitrooxyacetyl moieties had
      different electrophilic properties. The benzoheterocycle parent structures were
      selected because of their reported bioactivities. Compounds bearing a methoxy
      group at the 6-position of the benzo[b]furan skeleton, were identified as potent
      antiproliferative agents against the human chronic myelogenous K562 and murine
      L1210 leukemia cell lines. Comparison of positional isomers indicated that moving
      the methoxy group from the 6- to the 5- or 7-position yielded inactive compounds.
      The effects of a selected series of compounds on cell cycle progression
      correlated well with their strong antiproliferative activity and inhibition of
      tubulin polymerization. The analysis of structure-activity relationships observed
      in the series of compounds described here may represent a platform for the design
      of more active molecules.

PMID- 20676360
TI  - A Ventral Prefrontal-Amygdala Neural System in Bipolar Disorder: A View from
      Neuroimaging Research.
AB  - In the past decade, neuroimaging research has identified key components in the
      neural system that underlies bipolar disorder (BD). The ventral prefrontal cortex
      (VPFC) and amygdala are highly interconnected structures that jointly play a
      central role in emotional regulation. Numerous research groups have reported
      prominent structural and functional abnormalities within the VPFC and amygdala
      supporting their essential role in a neural system underlying the emotional
      dysregulation that is a core feature of BD. Findings in BD also include those in
      brain regions interconnected with the VPFC and amygdala, including the ventral
      striatum, hippocampus, and the cerebellum. Abnormalities in these regions may
      contribute to symptoms that reflect disruption in functions subserved by these
      structures, including motivational, mnemonic and psychomotor functions.This
      article will first review leads from behavioral neurology that implicated these
      neural system abnormalities in BD. It will then review findings from structural
      imaging and functional imaging studies to support the presence of abnormalities
      within these neural system components in BD. It will also review new findings
      from studies using diffusion tensor imaging (DTI) that provide increasing
      evidence of abnormalities in the connections between these neural system
      components in BD. Emerging data supporting differences in this neural system
      during adolescence, as well as potential beneficial effects of treatment on
      structure and function will also be presented. Finally, the article will discuss
      the implications for future investigations, including those for early
      identification and treatment of BD.

PMID- 20676362
TI  - Diversity of HIV-1 subtype B: implications to the origin of BF recombinants.
AB  - BACKGROUND: The HIV-1 subtype B epidemic in Brazil is peculiar because of the
      high frequency of isolates having the GWGR tetramer at V3 loop region. It has
      been suggested that GWGR is a distinct variant and less pathogenic than other
      subtype B isolates. METHODOLOGY/PRINCIPAL FINDINGS: Ninety-four percent of the
      HIV-1 subtype B worldwide sequences (7689/8131) obtained from the Los Alamos HIV
      database contain proline at the tetramer of the V3 loop of the env gene (GPGR)
      and only 0.74% (60/8131) have tryptophan (GWGR). By contrast, 48.4% (161/333) of
      subtype B isolates from Brazil have proline, 30.6% (102/333) contain tryptophan
      and 10.5% (35/333) have phenylalanine (F) at the second position of the V3 loop
      tip. The proportion of tryptophan and phenylalanine in Brazilian isolates is much
      higher than in worldwide subtype B sequences (chi-square test, p = 0.0001). The
      combined proportion of proline, tryptophan and phenylalanine (GPGR+GWGR+GFGR) of
      Brazilian isolates corresponds to 89% of all amino acids in the V3 loop.
      Phylogenetic analysis revealed that almost all subtype B isolates in Brazil have
      a common origin regardless of their motif (GWGR, GPGR, GGGR, etc.) at the V3
      tetramer. This shared ancestral origin was also observed in CRF28_BF and CRF29_BF
      in a genome region (free of recombination) derived from parental subtype B. These
      results imply that tryptophan substitution (e.g., GWGR-to-GxGR), which was
      previously associated with the change in the coreceptor usage within the host,
      also occurs at the population level. CONCLUSIONS/SIGNIFICANCE: Based on the
      current findings and previous study showing that tryptophan and phenylalanine in
      the V3 loop are related with coreceptor usage, we propose that tryptophan and
      phenylalanine in subtype B isolates in Brazil are kept by selective mechanisms
      due to the distinct coreceptor preferences in target cells of GWGR, GFGR and GFGR
      viruses.

PMID- 20676363
TI  - Characterization of Dengue virus type 2: new insights on the 2010 Brazilian
      epidemic.
AB  - Dengue viruses (DENV) serotypes 1, 2, and 3 have been causing yearly outbreaks in
      Brazil. In this study, we report the re-introduction of DENV2 in the coast of Sao
      Paulo State. Partial envelope viral genes were sequenced from eighteen patients
      with dengue fever during the 2010 epidemic. Phylogenetic analysis showed this
      strain belongs to the American/Asian genotype and was closely related to the
      virus that circulated in Rio de Janeiro in 2007 and 2008. The phylogeny also
      showed no clustering by clinical presentation, suggesting that the disease
      severity could not be explained by distinct variants or genotypes. The time of
      the most recent common ancestor of American/Asian genotype and the Sao Paulo and
      Rio de Janeiro (SP/RJ) monophyletic cluster was estimated to be around 40 and 10
      years, respectively. Since this virus was first identified in Brazil in 2007, we
      suggest that it was already circulating in the country before causing the first
      documented outbreak. This is the first description of the 2010 outbreak in the
      State of Sao Paulo, Brazil, and should contribute to efforts to control and
      monitor the spread of DENVs in endemic areas.

PMID- 20676364
TI  - Cocaine is low on the value ladder of rats: possible evidence for resilience to
      addiction.
AB  - BACKGROUND: Assessing the relative value of cocaine and how it changes with
      chronic drug use represents a long-standing goal in addiction research.
      Surprisingly, recent experiments in rats--by far the most frequently used animal
      model in this field--suggest that the value of cocaine is lower than previously
      thought. METHODOLOGY/PRINCIPAL FINDINGS: Here we report a series of choice
      experiments that better define the relative position of cocaine on the value
      ladder of rats (i.e., preference rank-ordering of different rewards). Rats were
      allowed to choose either taking cocaine or drinking water sweetened with
      saccharin--a nondrug alternative that is not biologically essential. By
      systematically varying the cost and concentration of sweet water, we found that
      cocaine is low on the value ladder of the large majority of rats, near the lowest
      concentrations of sweet water. In addition, a retrospective analysis of all
      experiments over the past 5 years revealed that no matter how heavy was past
      cocaine use most rats readily give up cocaine use in favor of the nondrug
      alternative. Only a minority, fewer than 15% at the heaviest level of past
      cocaine use, continued to take cocaine, even when hungry and offered a natural
      sugar that could relieve their need of calories. CONCLUSIONS/SIGNIFICANCE: This
      pattern of results (cocaine abstinence in most rats; cocaine preference in few
      rats) maps well onto the epidemiology of human cocaine addiction and suggests
      that only a minority of rats would be vulnerable to cocaine addiction while the
      large majority would be resilient despite extensive drug use. Resilience to drug
      addiction has long been suspected in humans but could not be firmly established,
      mostly because it is difficult to control retrospectively for differences in drug
      self-exposure and/or availability in human drug users. This conclusion has
      important implications for preclinical research on the neurobiology of cocaine
      addiction and for future medication development.

PMID- 20676365
TI  - Cord blood stem cell-mediated induction of apoptosis in glioma downregulates X
      linked inhibitor of apoptosis protein (XIAP).
AB  - BACKGROUND: XIAP (X-linked inhibitor of apoptosis protein) is one of the most
      important members of the apoptosis inhibitor family. XIAP is upregulated in
      various malignancies, including human glioblastoma. It promotes invasion,
      metastasis, growth and survival of malignant cells. We hypothesized that
      downregulation of XIAP by human umbilical cord blood mesenchymal stem cells
      (hUCBSC) in glioma cells would cause them to undergo apoptotic death.
      METHODOLOGY/PRINCIPAL FINDINGS: We observed the effect of hUCBSC on two malignant
      glioma cell lines (SNB19 and U251) and two glioma xenograft cell lines (4910 and
      5310). In co-cultures of glioma cells with hUCBSC, proliferation of glioma cells
      was significantly inhibited. This is associated with increased cytotoxicity of
      glioma cells, which led to glioma cell death. Stem cells induced apoptosis in
      glioma cells, which was evaluated by TUNEL assay, FACS analyses and
      immunoblotting. The induction of apoptosis is associated with inhibition of XIAP
      in co-cultures of hUCBSC. Similar results were obtained by the treatment of
      glioma cells with shRNA to downregulate XIAP (siXIAP). Downregulation of XIAP
      resulted in activation of caspase-3 and caspase-9 to trigger apoptosis in glioma
      cells. Apoptosis is characterized by the loss of mitochondrial membrane potential
      and upregulation of mitochondrial apoptotic proteins Bax and Bad. Cell death of
      glioma cells was marked by downregulation of Akt and phospho-Akt molecules. We
      observed similar results under in vivo conditions in U251- and 5310-injected nude
      mice brains, which were treated with hUCBSC. Under in vivo conditions,
      Smac/DIABLO was found to be colocalized in the nucleus, showing that hUCBSC
      induced apoptosis is mediated by inhibition of XIAP and activation of
      Smac/DIABLO. CONCLUSIONS/SIGNIFICANCE: Our results indicate that downregulation
      of XIAP by hUCBSC treatment induces apoptosis, which led to the death of the
      glioma cells and xenograft cells. This study demonstrates the therapeutic
      potential of XIAP and hUCBSC to treat malignant gliomas.

PMID- 20676366
TI  - Gene expression profiling of the local cecal response of genetic chicken lines
      that differ in their susceptibility to Campylobacter jejuni colonization.
AB  - Campylobacter jejuni (C. jejuni) is one of the most common causes of human
      bacterial enteritis worldwide primarily due to contaminated poultry products.
      Previously, we found a significant difference in C. jejuni colonization in the
      ceca between two genetically distinct broiler lines (Line A (resistant) has less
      colony than line B (susceptible) on day 7 post inoculation). We hypothesize that
      different mechanisms between these two genetic lines may affect their ability to
      resist C. jejuni colonization in chickens. The molecular mechanisms of the local
      host response to C. jejuni colonization in chickens have not been well
      understood. In the present study, to profile the cecal gene expression in the
      response to C. jejuni colonization and to compare differences between two lines
      at the molecular level, RNA of ceca from two genetic lines of chickens (A and B)
      were applied to a chicken whole genome microarray for a pair-comparison between
      inoculated (I) and non-inoculated (N) chickens within each line and between
      lines. Our results demonstrated that metabolism process and insulin receptor
      signaling pathways are key contributors to the different response to C. jejuni
      colonization between lines A and B. With C. jejuni inoculation, lymphocyte
      activation and lymphoid organ development functions are important for line A host
      defenses, while cell differentiation, communication and signaling pathways are
      important for line B. Interestingly, circadian rhythm appears play a critical
      role in host response of the more resistant A line to C. jejuni colonization. A
      dramatic differential host response was observed between these two lines of
      chickens. The more susceptible line B chickens responded to C. jejuni inoculation
      with a dramatic up-regulation in lipid, glucose, and amino acid metabolism, which
      is undoubtedly for use in the response to the colonization with little or no
      change in immune host defenses. However, in more resistant line A birds the host
      defense responses were characterized by an up-regulation lymphocyte activation,
      probably by regulatory T cells and an increased expression of the NLR recognition
      receptor NALP1. To our knowledge, this is the first time each of these responses
      has been observed in the avian response to an intestinal bacterial pathogen.

PMID- 20676367
TI  - Applauding with closed hands: neural signature of action-sentence compatibility
      effects.
AB  - BACKGROUND: Behavioral studies have provided evidence for an action-sentence
      compatibility effect (ACE) that suggests a coupling of motor mechanisms and
      action-sentence comprehension. When both processes are concurrent, the action
      sentence primes the actual movement, and simultaneously, the action affects
      comprehension. The aim of the present study was to investigate brain markers of
      bidirectional impact of language comprehension and motor processes.
      METHODOLOGY/PRINCIPAL FINDINGS: Participants listened to sentences describing an
      action that involved an open hand, a closed hand, or no manual action. Each
      participant was asked to press a button to indicate his/her understanding of the
      sentence. Each participant was assigned a hand-shape, either closed or open,
      which had to be used to activate the button. There were two groups (depending on
      the assigned hand-shape) and three categories (compatible, incompatible and
      neutral) defined according to the compatibility between the response and the
      sentence. ACEs were found in both groups. Brain markers of semantic processing
      exhibited an N400-like component around the Cz electrode position. This component
      distinguishes between compatible and incompatible, with a greater negative
      deflection for incompatible. Motor response elicited a motor potential (MP) and a
      re-afferent potential (RAP), which are both enhanced in the compatible condition.
      CONCLUSIONS/SIGNIFICANCE: The present findings provide the first ACE cortical
      measurements of semantic processing and the motor response. N400-like effects
      suggest that incompatibility with motor processes interferes in sentence
      comprehension in a semantic fashion. Modulation of motor potentials (MP and RAP)
      revealed a multimodal semantic facilitation of the motor response. Both results
      provide neural evidence of an action-sentence bidirectional relationship. Our
      results suggest that ACE is not an epiphenomenal post-sentence comprehension
      process. In contrast, motor-language integration occurring during the verb onset
      supports a genuine and ongoing brain motor-language interaction.

PMID- 20676368
TI  - Differential modulation of TCF/LEF-1 activity by the soluble LRP6-ICD.
AB  - The canonical Wnt/beta-catenin (Wnt) pathway is a master transcriptional
      regulatory signaling pathway that controls numerous biological processes
      including proliferation and differentiation. As such, transcriptional activity of
      the Wnt pathway is tightly regulated and/or modulated by numerous proteins at the
      level of the membrane, cytosol and/or nucleus. In the nucleus, transcription of
      Wnt target genes by TCF/LEF-1 is repressed by the long Groucho/TLE co-repressor
      family. However, a truncated member of the Groucho/TLE family, amino terminal
      enhancer of Split (AES) can positively modulate TCF/LEF-1 activity by
      antagonizing long Groucho/TLE members in a dominant negative manner. We have
      previously shown the soluble intracellular domain of the LRP6 receptor, a
      receptor required for activation of the Wnt pathway, can positively regulate
      transcriptional activity within the Wnt pathway. In the current study, we show
      the soluble LRP6 intracellular domain (LRP6-ICD) can also translocate to the
      nucleus in CHO and HEK 293T cells and in contrast to cytosolic LRP6-ICD; nuclear
      LRP6-ICD represses TCF/LEF-1 activity. In agreement with previous reports, we
      show AES enhances TCF/LEF-1 mediated reporter transcription and further we
      demonstrate that AES activity is spatially regulated in HEK 293T cells. LRP6-ICD
      interacts with AES exclusively in the nucleus and represses AES mediated TCF/LEF
      1 reporter transcription. These results suggest that LRP6-ICD can differentially
      modulate Wnt pathway transcriptional activity depending upon its subcellular
      localization and differential protein-protein interactions.

PMID- 20676369
TI  - Light perception in two strictly subterranean rodents: life in the dark or blue?
AB  - BACKGROUND: The African mole-rats (Bathyergidae, Rodentia) are strictly
      subterranean, congenitally microphthalmic rodents that are hardly ever exposed to
      environmental light. Because of the lack of an overt behavioural reaction to
      light, they have long been considered to be blind. However, recent anatomical
      studies have suggested retention of basic visual capabilities. In this study, we
      employed behavioural tests to find out if two mole-rat species are able to
      discriminate between light and dark, if they are able to discriminate colours
      and, finally, if the presence of light in burrows provokes plugging behaviour,
      which is assumed to have a primarily anti-predatory function.
      METHODOLOGY/PRINCIPAL FINDING: We used a binary choice test to show that the
      silvery mole-rat Heliophobius argenteocinereus and the giant mole-rat Fukomys
      mechowii exhibit a clear photoavoidance response to full-spectrum ("white"), blue
      and green-yellow light, but no significant reaction to ultraviolet or red light
      during nest building. The mole-rats thus retain dark/light discrimination
      capabilities and a capacity to perceive short to medium-wavelength light in the
      photopic range of intensities. These findings further suggest that the mole-rat S
      opsin has its absorption maximum in the violet/blue part of the spectrum. The
      assay did not yield conclusive evidence regarding colour discrimination. To test
      the putative role of vision in bathyergid anti-predatory behaviour, we examined
      the reaction of mole-rats to the incidence of light in an artificial burrow
      system. The presence of light in the burrow effectively induced plugging of the
      illuminated tunnel. CONCLUSION/SIGNIFICANCE: Our findings suggest that the
      photopic vision is conserved and that low acuity residual vision plays an
      important role in predator avoidance and tunnel maintenance in the African mole
      rats.

PMID- 20676370
TI  - Two hemocyte lineages exist in silkworm larval hematopoietic organ.
AB  - BACKGROUND: Insects have multiple hemocyte morphotypes with different functions
      as do vertebrates, however, their hematopoietic lineages are largely unexplored
      with the exception of Drosophila melanogaster. METHODOLOGY/PRINCIPAL FINDINGS: To
      study the hematopoietic lineage of the silkworm, Bombyx mori, we investigated in
      vivo and in vitro differentiation of hemocyte precursors in the hematopoietic
      organ (HPO) into the four mature hemocyte subsets, namely, plasmatocytes,
      granulocytes, oenocytoids, and spherulocytes. Five days after implantation of
      enzymatically-dispersed HPO cells from a GFP-expressing transgenic line into the
      hemocoel of normal larvae, differentiation into plasmatocytes, granulocytes and
      oenocytoids, but not spherulocytes, was observed. When the HPO cells were
      cultured in vitro, plasmatocytes appeared rapidly, and oenocytoids possessing
      prophenol oxidase activity appeared several days later. HPO cells were also able
      to differentiate into a small number of granulocytes, but not into spherulocytes.
      When functionally mature plasmatocytes were cultured in vitro, oenocytoids were
      observed 10 days later. These results suggest that the hemocyte precursors in HPO
      first differentiate into plasmatocytes, which further change into oenocytoids.
      CONCLUSIONS/SIGNIFICANCE: From these results, we propose that B. mori hemocytes
      can be divided into two major lineages, a granulocyte lineage and a plasmatocyte
      oenocytoid lineage. The origins of the spherulocytes could not be determined in
      this study. We construct a model for the hematopoietic lineages at the larval
      stage of B. mori.

PMID- 20676371
TI  - Good and bad in the hands of politicians: spontaneous gestures during positive
      and negative speech.
AB  - BACKGROUND: According to the body-specificity hypothesis, people with different
      bodily characteristics should form correspondingly different mental
      representations, even in highly abstract conceptual domains. In a previous test
      of this proposal, right- and left-handers were found to associate positive ideas
      like intelligence, attractiveness, and honesty with their dominant side and
      negative ideas with their non-dominant side. The goal of the present study was to
      determine whether 'body-specific' associations of space and valence can be
      observed beyond the laboratory in spontaneous behavior, and whether these
      implicit associations have visible consequences. METHODOLOGY AND PRINCIPAL
      FINDINGS: We analyzed speech and gesture (3012 spoken clauses, 1747 gestures)
      from the final debates of the 2004 and 2008 US presidential elections, which
      involved two right-handers (Kerry, Bush) and two left-handers (Obama, McCain).
      Blind, independent coding of speech and gesture allowed objective hypothesis
      testing. Right- and left-handed candidates showed contrasting associations
      between gesture and speech. In both of the left-handed candidates, left-hand
      gestures were associated more strongly with positive-valence clauses and right
      hand gestures with negative-valence clauses; the opposite pattern was found in
      both right-handed candidates. CONCLUSIONS: Speakers associate positive messages
      more strongly with dominant hand gestures and negative messages with non-dominant
      hand gestures, revealing a hidden link between action and emotion. This pattern
      cannot be explained by conventions in language or culture, which associate 'good'
      with 'right' but not with 'left'; rather, results support and extend the body
      specificity hypothesis. Furthermore, results suggest that the hand speakers use
      to gesture may have unexpected (and probably unintended) communicative value,
      providing the listener with a subtle index of how the speaker feels about the
      content of the co-occurring speech.

PMID- 20676372
TI  - Central crosstalk for somatic tinnitus: abnormal vergence eye movements.
AB  - BACKGROUND: Frequent oulomotricity problems with orthoptic testing were reported
      in patients with tinnitus. This study examines with objective recordings vergence
      eye movements in patients with somatic tinnitus patients with ability to modify
      their subjective tinnitus percept by various movements, such as jaw, neck, eye
      movements or skin pressure. METHODS: Vergence eye movements were recorded with
      the Eyelink II video system in 15 (23-63 years) control adults and 19 (36-62
      years) subjects with somatic tinnitus. FINDINGS: 1) Accuracy of divergence but
      not of convergence was lower in subjects with somatic tinnitus than in control
      subjects. 2) Vergence duration was longer and peak velocity was lower in subjects
      with somatic tinnitus than in control subjects. 3) The number of embedded
      saccades and the amplitude of saccades coinciding with the peak velocity of
      vergence were higher for tinnitus subjects. Yet, saccades did not increase peak
      velocity of vergence for tinnitus subjects, but they did so for controls. 4) In
      contrast, there was no significant difference of vergence latency between these
      two groups. INTERPRETATION: The results suggest dysfunction of vergence areas
      involving cortical-brainstem-cerebellar circuits. We hypothesize that central
      auditory dysfunction related to tinnitus percept could trigger mild cerebellar
      brainstem dysfunction or that tinnitus and vergence dysfunction could both be
      manifestations of mild cortical-brainstem-cerebellar syndrome reflecting abnormal
      cross-modality interactions between vergence eye movements and auditory signals.

PMID- 20676374
TI  - The risk and timing of tuberculosis diagnosed in smear-negative TB suspects: a 12
      month cohort study in Harare, Zimbabwe.
AB  - BACKGROUND: Cases of smear-negative TB have increased dramatically in high
      prevalence HIV settings and pose considerable diagnostic and management
      challenges. METHODS AND FINDINGS: Between February 2006 and July 2007, a cohort
      study nested within a cluster-randomised trial of community-based case finding
      strategies for TB in Harare, Zimbabwe was undertaken. Participants who had
      negative sputum smears and remained symptomatic of TB were follow-up for one year
      with standardised investigations including HIV testing, repeat sputum smears, TB
      culture and chest radiography. Defaulters were actively traced to the community.
      The objectives were to investigate the incidence and risk factors for TB. TB was
      diagnosed in 218 (18.2%) participants, of which 39.4% was bacteriologically
      confirmed. Most cases (84.2%) were diagnosed within 3 months, but TB incidence
      remained high thereafter (111.3 per 1000 person-years, 95% CI: 86.6 to 146.3).
      HIV prevalence was 63.3%, and HIV-infected individuals had a 3.5-fold higher risk
      of tuberculosis than HIV-negative individuals. CONCLUSION: We found that
      diagnosis of TB was insensitive and slow, even with early radiography and
      culture. Until more sensitive and rapid diagnostic tests become widely available,
      a much more proactive and integrated approach towards prompt initiation of ART,
      ideally from within TB clinics and without waiting for TB to be excluded, is
      needed to minimise the risk and consequences of diagnostic delay.

PMID- 20676373
TI  - Live cell monitoring of hiPSC generation and differentiation using differential
      expression of endogenous microRNAs.
AB  - Human induced pluripotent stem cells (hiPSCs) provide new possibilities for
      regenerative therapies. In order for this potential to be achieved, it is
      critical to efficiently monitor the differentiation of these hiPSCs into specific
      lineages. Here, we describe a lentiviral reporter vector sensitive to specific
      microRNAs (miRNA) to show that a single vector bearing multiple miRNA target
      sequences conjugated to different reporters can be used to monitor hiPSC
      formation and subsequent differentiation from human fetal fibroblasts (HFFs). The
      reporter vector encodes EGFP conjugated to the targets of human embryonic stem
      cell (hESC) specific miRNAs (miR-302a and miR-302d) and mCherry conjugated to the
      targets of differentiated cells specific miRNAs (miR-142-3p, miR-155, and miR
      223). The vector was used to track reprogramming of HFF to iPSC. HFFs co
      transduced with this reporter vector and vectors encoding 4 reprogramming factors
      (OCT4, SOX2, KLF4 and cMYC) were mostly positive for EGFP (67%) at an early stage
      of hiPSC formation. EGFP expression gradually disappeared and mCherry expression
      increased indicating less miRNAs specific to differentiated cells and expression
      of miRNAs specific to hESCs. Upon differentiation of the hiPSC into embryoid
      bodies, a large fraction of these hiPSCs regained EGFP expression and some of
      those cells became single positive for EGFP. Further differentiation into neural
      lineages showed distinct structures demarcated by either EGFP or mCherry
      expression. These findings demonstrate that a miRNA dependent reporter vector can
      be a useful tool to monitor living cells during reprogramming of hiPSC and
      subsequent differentiation to lineage specific cells.

PMID- 20676375
TI  - Tourniquet-applied upper limb orthopaedic surgery results in increased
      inflammation and changes to leukocyte, coagulation and endothelial markers.
AB  - PURPOSE: During this pilot clinical study, patients scheduled for elective
      tourniquet-applied upper limb orthopaedic surgery were recruited to investigate
      the effects of surgery on various biological markers (n = 10 patients). METHODS:
      Three venous blood samples were collected from the arm at the ante-cubital fossa,
      at baseline (pre-operatively), 5 and 15 minutes after reperfusion (post
      operatively). Neutrophil and monocyte leukocyte sub-populations were isolated by
      density gradient centrifugation techniques. Leukocyte activation was investigated
      by measuring the cell surface expression of CD62L (L-selectin), CD11b (Mac-1) and
      the intracellular production of hydrogen peroxide (H2O2), via flow cytometry. C
      reactive protein (CRP) was measured using a clinical chemistry analyser. Plasma
      concentrations of protein C and von Willebrand factor (vWF) were measured using
      enzyme-linked fluorescent assays (ELFA). RESULTS: Following tourniquet-applied
      upper limb orthopaedic surgery, there was a decrease in neutrophil CD62L
      expression (p = 0.001), an increase in CD11b expression and in the intracellular
      production of H2O2 by neutrophils and monocytes (p<0.05). An increase in CRP
      concentration (p<0.001), a decrease in protein C concentration (p = 0.004), with
      a trend towards elevated vWF levels (p = 0.232) were also observed during this
      time. CONCLUSIONS: Conventionally, patients undergoing orthopaedic surgery have
      been monitored in the peri-operative period by means of CRP, which is a non
      specific marker of inflammation. This test cannot differentiate between
      inflammation due to current or pre-existing disease processes and the development
      of ischaemia-reperfusion injury surgery. The findings from this study suggest
      that markers such as CD11b, protein C and H2O2 may provide alternative ways of
      assessing leukocyte and coagulation activation peri-operatively. It is proposed
      that by allowing orthopaedic surgeons access to laboratory markers such as CD11b,
      protein C and H2O2, an accurate assessment of the extent of inflammation due to
      surgery per se could be made.

PMID- 20676376
TI  - Genome sequencing reveals widespread virulence gene exchange among human
      Neisseria species.
AB  - Commensal bacteria comprise a large part of the microbial world, playing
      important roles in human development, health and disease. However, little is
      known about the genomic content of commensals or how related they are to their
      pathogenic counterparts. The genus Neisseria, containing both commensal and
      pathogenic species, provides an excellent opportunity to study these issues. We
      undertook a comprehensive sequencing and analysis of human commensal and
      pathogenic Neisseria genomes. Commensals have an extensive repertoire of
      virulence alleles, a large fraction of which has been exchanged among Neisseria
      species. Commensals also have the genetic capacity to donate DNA to, and take up
      DNA from, other Neisseria. Our findings strongly suggest that commensal Neisseria
      serve as reservoirs of virulence alleles, and that they engage extensively in
      genetic exchange.

PMID- 20676377
TI  - Different susceptibility to the Parkinson's toxin MPTP in mice lacking the redox
      master regulator Nrf2 or its target gene heme oxygenase-1.
AB  - BACKGROUND: The transcription factor Nrf2 (NF-E2-related factor 2) and its target
      gene products, including heme oxygenase-1 (HO-1), elicit an antioxidant response
      that may have therapeutic value for Parkinson's disease (PD). However, HO-1
      protein levels are increased in dopaminergic neurons of Parkinson's disease (PD)
      patients, suggesting its participation in free-iron deposition, oxidative stress
      and neurotoxicity. Before targeting Nrf2 for PD therapy it is imperative to
      determine if HO-1 is neurotoxic or neuroprotective in the basal ganglia.
      METHODOLOGY: We addressed this question by comparing neuronal damage and gliosis
      in Nrf2- or HO-1-knockout mice submitted to intraperitoneal injection of 1-methyl
      4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for five consecutive days. Nrf2
      knockout mice showed exacerbated gliosis and dopaminergic nigrostriatal
      degeneration, as determined by immunohistochemical staining of tyrosine
      hydroxylase in striatum (STR) and substantia nigra (SN) and by HPLC determination
      of striatal dopamine and 3,4- dihydroxyphenylacetic acid (DOPAC). On the other
      hand, the severity of gliosis and dopaminergic degeneration in HO-1-null mice was
      neither increased nor reduced. Regarding free-iron deposition, both Nrf2- and HO
      1-deficient mice exhibited similar number of deposits as determined by Perl's
      staining, therefore indicating that these proteins do not contribute
      significantly to iron accumulation or clearance in MPTP-induced Parkinsonism.
      CONCLUSIONS: These results suggest that HO-1 does not protect or enhance the
      sensitivity to neuronal death in Parkinson's disease and that pharmacological or
      genetic intervention on Nrf2 may provide a neuroprotective benefit as add on
      therapy with current symptomatic protocols.

PMID- 20676378
TI  - Unlocking short read sequencing for metagenomics.
AB  - BACKGROUND: Different high-throughput nucleic acid sequencing platforms are
      currently available but a trade-off currently exists between the cost and number
      of reads that can be generated versus the read length that can be achieved.
      METHODOLOGY/PRINCIPAL FINDINGS: We describe an experimental and computational
      pipeline yielding millions of reads that can exceed 200 bp with quality scores
      approaching that of traditional Sanger sequencing. The method combines an
      automatable gel-less library construction step with paired-end sequencing on a
      short-read instrument. With appropriately sized library inserts, mate-pair
      sequences can overlap, and we describe the SHERA software package that joins them
      to form a longer composite read. CONCLUSIONS/SIGNIFICANCE: This strategy is
      broadly applicable to sequencing applications that benefit from low-cost high
      throughput sequencing, but require longer read lengths. We demonstrate that our
      approach enables metagenomic analyses using the Illumina Genome Analyzer, with
      low error rates, and at a fraction of the cost of pyrosequencing.

PMID- 20676379
TI  - Metabolomic and transcriptomic analysis of the rice response to the bacterial
      blight pathogen Xanthomonas oryzae pv. oryzae.
AB  - Bacterial leaf blight (BLB), caused by Xanthomonas oryzae pv. oryzae (Xoo), gives
      rise to devastating crop losses in rice. Disease resistant rice cultivars are the
      most economical way to combat the disease. The TP309 cultivar is susceptible to
      infection by Xoo strain PXO99. A transgenic variety, TP309_Xa21, expresses the
      pattern recognition receptor Xa21, and is resistant. PXO99 big up tri, openraxST,
      a strain lacking the raxST gene, is able to overcome Xa21-mediated immunity. We
      used a single extraction solvent to demonstrate comprehensive metabolomics and
      transcriptomics profiling under sample limited conditions, and analyze the
      molecular responses of two rice lines challenged with either PXO99 or PXO99 big
      up tri, openraxST. LC-TOF raw data file filtering resulted in better within group
      reproducibility of replicate samples for statistical analyses. Accurate mass
      match compound identification with molecular formula generation (MFG) ranking of
      355 masses was achieved with the METLIN database. GC-TOF analysis yielded an
      additional 441 compounds after BinBase database processing, of which 154 were
      structurally identified by retention index/MS library matching. Multivariate
      statistics revealed that the susceptible and resistant genotypes possess distinct
      profiles. Although few mRNA and metabolite differences were detected in PXO99
      challenged TP309 compared to mock, many differential changes occurred in the Xa21
      mediated response to PXO99 and PXO99 big up tri, openraxST. Acetophenone,
      xanthophylls, fatty acids, alkaloids, glutathione, carbohydrate and lipid
      biosynthetic pathways were affected. Significant transcriptional induction of
      several pathogenesis related genes in Xa21 challenged strains, as well as
      differential changes to GAD, PAL, ICL1 and Glutathione-S-transferase transcripts
      indicated limited correlation with metabolite changes under single time point
      global profiling conditions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online
      version of this article (doi:10.1007/s11306-010-0218-7) contains supplementary
      material, which is available to authorized users.

PMID- 20676381
TI  - Gender effects in spatial orientation: cognitive profiles and mental strategies.
AB  - Experimental evidence and meta-analyses offer some support for gender-related
      differences in visuo-spatial ability. However, few studies addressed this issue
      in an ecological context and/or in everyday tasks implying spatial abilities,
      such as geographical orientation. Moreover, the relation of specific strategies
      and gender is still unclear. In the present investigation, we compared men and
      women in a newly designed battery of spatial orientation tasks in which landmark,
      route and survey knowledge were considered. In addition, four visuo-spatial
      working memory (VSWM) tasks were presented. Significant differences favouring men
      in VSWM tasks were reported, supporting existing evidence. However, men and women
      did not significantly differ in orientation tasks performance. The patterns of
      correlation between working memory and spatial orientation tasks indicated that
      men and women used somewhat different strategies in carrying out the orientation
      tasks. In particular, active processes seem to play a greater role in females'
      performance, thus confirming the importance of this variable in interpreting
      gender effect in VSWM tasks. Altogether, results indicate that gender effects
      could well result from differences in cognitive strategies and support data
      indicating that adequate training could reduce or eliminate them. Copyright (c)
      2004 John Wiley & Sons, Ltd.

PMID- 20676380
TI  - G-quadruplex DNA sequences are evolutionarily conserved and associated with
      distinct genomic features in Saccharomyces cerevisiae.
AB  - G-quadruplex DNA is a four-stranded DNA structure formed by non-Watson-Crick base
      pairing between stacked sets of four guanines. Many possible functions have been
      proposed for this structure, but its in vivo role in the cell is still largely
      unresolved. We carried out a genome-wide survey of the evolutionary conservation
      of regions with the potential to form G-quadruplex DNA structures (G4 DNA motifs)
      across seven yeast species. We found that G4 DNA motifs were significantly more
      conserved than expected by chance, and the nucleotide-level conservation patterns
      suggested that the motif conservation was the result of the formation of G4 DNA
      structures. We characterized the association of conserved and non-conserved G4
      DNA motifs in Saccharomyces cerevisiae with more than 40 known genome features
      and gene classes. Our comprehensive, integrated evolutionary and functional
      analysis confirmed the previously observed associations of G4 DNA motifs with
      promoter regions and the rDNA, and it identified several previously unrecognized
      associations of G4 DNA motifs with genomic features, such as mitotic and meiotic
      double-strand break sites (DSBs). Conserved G4 DNA motifs maintained strong
      associations with promoters and the rDNA, but not with DSBs. We also performed
      the first analysis of G4 DNA motifs in the mitochondria, and surprisingly found a
      tenfold higher concentration of the motifs in the AT-rich yeast mitochondrial DNA
      than in nuclear DNA. The evolutionary conservation of the G4 DNA motif and its
      association with specific genome features supports the hypothesis that G4 DNA has
      in vivo functions that are under evolutionary constraint.

PMID- 20676382
TI  - Quantum Molecular Interaction Field Models of Substrate Enantioselection in
      Asymmetric Processes.
AB  - Computational models correlating substrate structure to enantioselection with
      asymmetric catalysts using the QMQSAR program are described. In addition to
      rapidly providing predictions that could be used to facilitate the screening of
      catalysts for novel substrates, the QMQSAR program identifies the portions of the
      substrate that most directly influence the enantioselectivity. The lack
      underlying relationship between all the substrates in one case, requires two
      quantitative structure selectivity relationships (QSSR) models to describe all of
      the experimental results.

PMID- 20676383
TI  - Low Pressure Vinylation of Aryl and Vinyl Halides via Heck-Mizoroki Reactions
      Using Ethylene.
AB  - Aryl bromides and iodides in the presence of catalytic amounts of a palladacycle
      derived from acetophenone oxime and 2 equivalents of potassium acetate react with
      ethylene under ambient pressure (15-30 psi) to give the corresponding
      vinylarenes. The reactions work with both electron-deficient and electron-rich
      aryl compounds and tolerate wide variety of common functional groups. Vinyl
      bromides lead to 1,3-dienes in moderate yields.

PMID- 20676384
TI  - Does cell lineage in the developing cerebral cortex contribute to its columnar
      organization?
AB  - Since the pioneer work of Lorente de No, Ramon y Cajal, Brodmann, Mountcastle,
      Hubel and Wiesel and others, the cerebral cortex has been seen as a jigsaw of
      anatomic and functional modules involved in the processing of different sets of
      information. In fact, a columnar distribution of neurons displaying similar
      functional properties throughout the cerebral cortex has been observed by many
      researchers. Although it has been suggested that much of the anatomical substrate
      for such organization would be already specified at early developmental stages,
      before activity-dependent mechanisms could take place, it is still unclear
      whether gene expression in the ventricular zone (VZ) could play a role in the
      development of discrete functional units, such as minicolumns or columns. Cell
      lineage experiments using replication-incompetent retroviral vectors have shown
      that the progeny of a single neuroepithelial/radial glial cell in the dorsal
      telencephalon is organized into discrete radial clusters of sibling excitatory
      neurons, which have a higher propensity for developing chemical synapses with
      each other rather than with neighboring non-siblings. Here, we will discuss the
      possibility that the cell lineage of single neuroepithelial/radial glia cells
      could contribute for the columnar organization of the neocortex by generating
      radial columns of sibling, interconnected neurons. Borrowing some concepts from
      the studies on cell-cell recognition and transcription factor networks, we will
      also touch upon the potential molecular mechanisms involved in the establishment
      of sibling-neuron circuits.

PMID- 20676386
TI  - The impact of progress indicators on task completion.
AB  - A near ubiquitous feature of user interfaces is feedback on task completion or
      progress indicators such as the graphical bar that grows as more of the task is
      completed. The presumed benefit is that users will be more likely to complete the
      task if they see they are making progress but it is also possible that feedback
      indicating slow progress may sometimes discourage users from completing the task.
      This paper describes two experiments that evaluate the impact of progress
      indicators on the completion of on-line questionnaires. In the first experiment,
      progress was displayed at different speeds throughout the questionnaire. If the
      early feedback indicated slow progress, abandonment rates were higher and users'
      subjective experience more negative than if the early feedback indicated faster
      progress. In the second experiment, intermittent feedback seemed to minimize the
      costs of discouraging feedback while preserving the benefits of encouraging
      feedback. Overall, the results suggest that when progress seems to outpace users'
      expectations, feedback can improve their experience though not necessarily their
      completion rates; when progress seems to lag behind what users expect, feedback
      degrades their experience and lowers completion rates.

PMID- 20676385
TI  - Characterization of the ebp(fm) pilus-encoding operon of Enterococcus faecium and
      its role in biofilm formation and virulence in a murine model of urinary tract
      infection.
AB  - We recently identified 15 genes encoding putative surface proteins with features
      of MSCRAMMs and/or pili in the Enterococcus faecium TX0016 (DO) genome, including
      four predicted pilus-encoding gene clusters; we also demonstrated that one of
      these, ebpABC(fm), is transcribed as an operon, that its putative major pilus
      subunit, EbpC(fm) (also called pilB), is polymerized into high molecular weight
      complexes, and that it is enriched among clinical E. faecium isolates. Here, we
      created a deletion of the ebpABC(fm) operon in an endocarditis-derived E. faecium
      strain (TX82) and showed, by a combination of whole-cell ELISA, flow cytometry,
      immunoblot and immunogold electron microscopy, that this deletion abolished
      EbpC(fm) expression and eliminated EbpC(fm)-containing pili from the cell
      surface. However, transcription of the downstream sortase, bps(fm), was not
      affected. Importantly, the ebpABC(fm) deletion resulted in significantly reduced
      biofilm formation (p < 0.0001) and initial adherence (p < 0.0001) versus the wild
      type; both were restored by complementing ebpABC(fm) in trans, which also
      restored cell surface expression of EbpC(fm) and pilus production. Furthermore,
      the deletion mutant was significantly attenuated in two independent mixed
      infection mouse urinary tract experiments, i.e., outnumbered by the wild-type in
      kidneys (p = 0.0003 and < 0.0001, respectively) and urinary bladders (p = 0.0003
      and = 0.002). In conclusion, we have shown that the ebpABC(fm) locus encodes pili
      on the E. faecium TX82 cell surface and provide the first evidence that pili of
      this emerging pathogen are important for its ability to form biofilm and to cause
      infection in an ascending UTI model.

PMID- 20676387
TI  - The Revised Hierarchical Model: A critical review and assessment.
AB  - Brysbaert and Duyck (2009) suggest that it is time to abandon the Revised
      Hierarchical Model (Kroll and Stewart, 1994) in favor of connectionist models
      such as BIA+ (Dijkstra and Van Heuven, 2002) that more accurately account for the
      recent evidence on nonselective access in bilingual word recognition. In this
      brief response, we first review the history of the Revised Hierarchical Model
      (RHM), consider the set of issues that it was proposed to address, and then
      evaluate the evidence that supports and fails to support the initial claims of
      the model. Although 15 years of new research findings require a number of
      revisions to the RHM, we argue that the central issues to which the model was
      addressed, the way in which new lexical forms are mapped to meaning and the
      consequence of language learning history for lexical processing, cannot be
      accounted for solely within models of word recognition.

PMID- 20676388
TI  - Treatment adherence to disease-modifying antirheumatic drugs in patients with
      rheumatoid arthritis and systemic lupus erythematosus.
AB  - Treatment adherence is critical in the management of rheumatic diseases. Recent
      advances in therapy for rheumatoid arthritis (RA) and systemic lupus
      erythematosus (SLE) are promising, although the impact on quality of life may be
      limited due to nonadherence. Databases including Ovid Medline, Scopus and the
      Epub-ahead-of-print subset of PubMed were searched for the period of the last 10
      years using combined keywords patient compliance, medication adherence, disease
      modifying antirheumatic drug (DMARD), rheumatoid arthritis and systemic lupus
      erythematosus. Additional references from retrieved papers were considered.
      Inclusion criteria were the following: identification of a quantitative measure
      of adherence to medications including DMARDs and biologics; inclusion of well
      defined measures of adherence; and patients with RA or SLE. Studies in RA and SLE
      patients demonstrated overall inadequate treatment adherence. Adherence was
      measured using multiple methods including pharmacy records, electronic
      monitoring, self-report and physician report. The evidence for interventions to
      improve treatment adherence was limited and demonstrated various results. Future
      research should further explore determinants of nonadherence and continue to
      examine the efficacy of implementing various strategies to improve medication
      management in this patient population.

PMID- 20676389
TI  - Roles of Glycinergic and Gamma-aminobutyric-ergic Mechanisms in the Micturition
      Reflex in Rats.
AB  - The micturition reflex is one of the autonomic reflexes mediated by the
      spinobulbospinal reflex pathway that passes through the pontine micturition
      center. In the central nervous system, glutamate is a major excitatory amino
      acid, while glycine and gamma-aminobutyric acid (GABA) are major inhibitory
      neurotransmitters and act to inhibit the micturition reflex at supraspinal and/or
      spinal sites. Glycine and GABA have additive or synergistic inhibitory effects on
      bladder activity. Hypofunction of glycinergic/GABAergic mechanisms in the
      lumbosacral spinal cord induces voiding dysfunctions, such as detrusor
      overactivity (DO) or detrusor-sphincter dyssynergia (DSD) after spinal cord
      injury (SCI) or bladder outlet obstruction in rats. Intrathecal, intravenous, or
      dietary glycine inhibits both bladder and urethral activity in normal and spinal
      cord injury (SCI) rats. Therefore, glycine might be a useful agent for the
      treatment of DO. Intrathecal muscimol and baclofen (GABA(A) and GABA(B) agonists,
      respectively) also inhibit non-voiding bladder contractions by suppressing C
      fiber bladder afferents in SCI rats. They also improve DSD by suppressing Onuf's
      nucleus and C-fiber bladder afferents. Baclofen is approved for the treatment of
      DO in SCI patients, but this agent has not been widely used because the
      therapeutic window of the drug is modest and the dose is limited by side-effects.
      Glutamic acid decraboxylase (GAD), the GABA synthesis enzyme, gene delivery by
      using non-replicating herpes simplex virus (HSV) vectors inhibits DO by
      suppressing C-fiber bladder afferents without affecting voiding contraction in
      SCI rats. Therefore, GAD gene therapy can restore urine storage function without
      affecting voiding function; it would be more beneficial than drug therapy for the
      treatment of urinary problems in SCI patients.

PMID- 20676390
TI  - Adult female hamsters avoid interspecific mating after exposure to heterospecific
      males.
AB  - When females mate with a heterospecific male, they do not usually produce viable
      offspring. Thus, there is a selective pressure for females to avoid interspecific
      mating. In many species, females innately avoid heterospecific males; females can
      also imprint on their parents to avoid later sexual interactions with
      heterospecific males. However, it was previously unknown whether adult females
      can learn to discriminate against heterospecific males. We tested the hypothesis
      that adult females previously unable to avoid interspecific mating learn to avoid
      such mating after being exposed to heterospecific males. Syrian hamster
      (Mesocricetus auratus) females not previously exposed to Turkish hamster
      (Mesocricetus brandti) males can discriminate between odors of conspecific and
      heterospecific males, but they mate with either type of male. However, when we
      exposed adult females to both a conspecific male and a heterospecific male
      through wire-mesh barriers for 8 days, and then paired them sequentially with the
      two males, females were more receptive to conspecific males and more aggressive
      to heterospecific males. When females were paired with the heterospecific male
      first and the conspecific male second, no female was receptive and all were
      aggressive to heterospecific males. When females were paired with the conspecific
      male first, only 43% of females were then aggressive toward the heterospecific
      male. That is, interactions with conspecific males may decrease a female's
      ability to properly avoid heterospecific males. Our study clearly shows for the
      first time that females can learn during adulthood to avoid interspecific mating
      just by being exposed to stimuli from heterospecific males.

PMID- 20676391
TI  - The Role of Basic Amino Acids in the Molecular Recognition of Hydroxyapatite by
      Statherin using Solid State NMR.
AB  - Organisms use proteins such as statherin to control the growth of hydroxyapatite
      (HAP), which is the principal component of teeth and bone. Though much emphasis
      has been placed on the acidic character of these proteins, the role of their
      basic amino acids is not well understood. In this work, solid state nuclear
      magnetic resonance was used to probe the interaction of the basic arginine side
      chains with the HAP surface. Statherin samples were individually labeled at each
      arginine site, and the distance to the surface was measured using the Rotational
      Echo DOuble Resonance (REDOR) technique. The results indicate a strong coupling
      between the R9 and R10 residues and the phosphorus atoms on the surface, with
      internuclear distances of 4.62 +/- 0.29 A and 4.53 +/- 0.16 A, respectively.
      Conversely, results also indicate weak coupling between R13 and the surface,
      suggesting this residue is more removed from the surface than R9 and R10.
      Combining these results with previous data, a new model for the molecular
      recognition of HAP by statherin is constructed.

PMID- 20676392
TI  - Confirmation of the Structures of Synthetic Derivatives of Migrastatin in the
      Light of Recently Disclosed Crystallographically Based Claims.
AB  - In the light of recently disclosed crystallographic studies on migrastatin ketone
      2 complex with fascin, the structures of migrastatin ketone 2 and migrastatin
      ether 4 have been re-evaluated by NMR and X-Ray crystallographic techniques. The
      results of these studies established the correctness of the previously reported
      structural assignment and confirm that the "small molecule" co-crystallized in
      complex with fascin is not the migrastatin ketone, which was provided for the
      infusion experiment, but rather its stereoisomer.

PMID- 20676393
TI  - Long-term Effects of Child Death on Parents' Health Related Quality of Life: A
      Dyadic Analysis.
AB  - This study examines the long-term effects of child death on bereaved parents'
      health-related quality of life (HRQoL). Using data from the Wisconsin
      Longitudinal Study, we compared 233 bereaved couples and 229 comparison couples
      (mean age = 65.11 years) and examined the life course effects of child death on
      parents' HRQoL. Variations in bereavement effects were examined by gender and for
      different causes of death. Bereaved parents had significantly worse HRQoL than
      comparison group parents, and there was no evidence of gender differences for
      this effect. With respect to the cause of a child's death, bereaved parents whose
      child died in violent circumstances had particularly low levels of HRQoL.
      Multilevel models indicated that marital closeness mitigated the negative effects
      of bereavement.

PMID- 20676394
TI  - Weight loss and incretin responsiveness improve glucose control independently
      after gastric bypass surgery.
AB  - BACKGROUND: The aim of the present study was to determine the mechanisms
      underlying Type 2 diabetes remission after gastric bypass (GBP) surgery by
      characterizing the short- and long-term changes in hormonal determinants of blood
      glucose. METHODS: Eleven morbidly obese women with diabetes were studied before
      and 1, 6, and 12 months after GBP; eight non-diabetic morbidly obese women were
      used as controls. The incretin effect was measured as the difference in insulin
      levels in response to oral glucose and to an isoglycemic intravenous challenge.
      Outcome measures were glucose, insulin, C-peptide, proinsulin, amylin, glucagon,
      glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP
      1) levels and the incretin effect on insulin secretion. RESULTS: The decrease in
      fasting glucose (r = 0.724) and insulin (r = 0.576) was associated with weight
      loss up to 12 months after GBP. In contrast, the blunted incretin effect
      (calculated at 22%) that improved at 1 month remained unchanged with further
      weight loss at 6 (52%) and 12 (52%) months. The blunted incretin (GLP-1 and GIP)
      levels, early phase insulin secretion, and other parameters of beta-cell function
      (amylin, proinsulin/insulin) followed the same pattern, with rapid improvement at
      1 month that remained unchanged at 1 year. CONCLUSIONS: The data suggest that
      weight loss and incretins may contribute independently to improved glucose levels
      in the first year after GBP surgery.

PMID- 20676395
TI  - Absence of inhibin alpha and retinoblastoma protein leads to early sertoli cell
      dysfunction.
AB  - Sertoli cells, the support cells of mammalian spermatogenesis, are regulated by a
      number of nuclear factors and express retinoblastoma (RB) tumor suppressor
      protein. We hypothesized that RB is an important mediator of Sertoli cell
      tumorigenesis in inhibin alpha knockout (Inha KO) mice. In our previous mouse
      studies, we found that conditional knockout (cKO) of Rb in Sertoli cells caused
      progressive Sertoli cell dysfunction. Initially, loss of RB had no gross effect
      on Sertoli cell function as the mice were fertile with normal testis weights at 6
      weeks of age, but by 10-14 weeks of age, mutant mice demonstrated severe Sertoli
      cell dysfunction and infertility. Although double knockout (dKO) of Rb and Inha
      did not result in exacerbation of the tumorigenic phenotype of Inha-null mice, we
      found that the dKO mice demonstrate an acceleration of Sertoli cell dysfunction
      compared to Rb cKO mice. Specifically, in contrast to Rb cKO mice, Inha/Rb dKO
      mice showed signs of Sertoli cell dysfunction as early as 4 weeks of age. These
      results demonstrate that RB is not essential for Sertoli cell tumorigenesis in
      Inha KO mice but that loss of Inha accelerates the infertility phenotype of Rb
      cKO mice.

PMID- 20676396
TI  - Emergence of variability in isogenic Escherichia coli populations infected by a
      filamentous virus.
AB  - The spread of epidemics not only depends on the average number of parasites
      produced per host, but also on the existence of highly infectious individuals. It
      is widely accepted that infectiousness depends on genetic and environmental
      determinants. However, even in clonal populations of host and viruses growing in
      homogeneous conditions, high variability can exist. Here we show that Escherichia
      coli cells commonly display high differentials in viral burst size, and address
      the kinetics of emergence of such variability with the non-lytic filamentous
      virus M13. By single-cell imaging of a virally-encoded fluorescent reporter, we
      monitor the viral charge distribution in infected bacterial populations at
      different time following infection. A mathematical model assuming autocatalytic
      virus replication and inheritance of bacterial growth rates quantitatively
      reproduces the experimental distributions, demonstrating that deterministic
      amplification of small host inhomogeneities is a mechanism sufficient to explain
      large and highly skewed distributions. This mechanism of amplification is general
      and may occur whenever a parasite has an initial phase of exponential growth
      within its host. Moreover, it naturally reproduces the shift towards higher
      virulence when the host is experimenting poor conditions, as observed commonly in
      host-parasite systems.

PMID- 20676397
TI  - A novel role for the centrosomal protein, pericentrin, in regulation of insulin
      secretory vesicle docking in mouse pancreatic beta-cells.
AB  - The centrosome is important for microtubule organization and cell cycle
      progression in animal cells. Recently, mutations in the centrosomal protein,
      pericentrin, have been linked to human microcephalic osteodysplastic primordial
      dwarfism (MOPD II), a rare genetic disease characterized by severe growth
      retardation and early onset of type 2 diabetes among other clinical
      manifestations. While the link between centrosomal and cell cycle defects may
      account for growth deficiencies, the mechanism linking pericentrin mutations with
      dysregulated glucose homeostasis and pre-pubertal onset of diabetes is unknown.
      In this report we observed abundant expression of pericentrin in quiescent
      pancreatic beta-cells of normal animals which led us to hypothesize that
      pericentrin may have a critical function in beta-cells distinct from its known
      role in regulating cell cycle progression. In addition to the typical centrosome
      localization, pericentrin was also enriched with secretory vesicles in the
      cytoplasm. Pericentrin overexpression in beta-cells resulted in aggregation of
      insulin-containing secretory vesicles with cytoplasmic, but not centrosomal,
      pericentriolar material and an increase in total levels of intracellular insulin.
      RNAi- mediated silencing of pericentrin in secretory beta-cells caused
      dysregulated secretory vesicle hypersecretion of insulin into the media.
      Together, these data suggest that pericentrin may regulate the intracellular
      distribution and secretion of insulin. Mice transplanted with pericentrin
      depleted islets exhibited abnormal fasting hypoglycemia and inability to regulate
      blood glucose normally during a glucose challenge, which is consistent with our
      in vitro data. This previously unrecognized function for a centrosomal protein to
      mediate vesicle docking in secretory endocrine cells emphasizes the adaptability
      of these scaffolding proteins to regulate diverse cellular processes and
      identifies a novel target for modulating regulated protein secretion in disorders
      such as diabetes.

PMID- 20676398
TI  - A global metabolic shift is linked to Salmonella multicellular development.
AB  - Bacteria can elaborate complex patterns of development that are dictated by
      temporally ordered patterns of gene expression, typically under the control of a
      master regulatory pathway. For some processes, such as biofilm development,
      regulators that initiate the process have been identified but subsequent
      phenotypic changes such as stress tolerance do not seem to be under the control
      of these same regulators. A hallmark feature of biofilms is growth within a self
      produced extracellular matrix. In this study we used metabolomics to compare
      Salmonella cells in rdar colony biofilms to isogenic csgD deletion mutants that
      do not produce an extracellular matrix. The two populations show distinct
      metabolite profiles. Even though CsgD controls only extracellular matrix
      production, metabolite signatures associated with cellular adaptations associated
      with stress tolerances were present in the wild type but not the mutant cells. To
      further explore these differences we examine the temporal gene expression of
      genes implicated in biofilm development and stress adaptations. In wild type
      cells, genes involved in a metabolic shift to gluconeogenesis and various stress
      resistance pathways exhibited an ordered expression profile timed with
      multicellular development even though they are not CsgD regulated. In csgD mutant
      cells, the ordered expression was lost. We conclude that the induction of these
      pathways results from production of, and growth within, a self produced matrix
      rather than elaboration of a defined genetic program. These results predict that
      common physiological properties of biofilms are induced independently of
      regulatory pathways that initiate biofilm formation.

PMID- 20676399
TI  - Highly pathogenic H5N1 influenza viruses carry virulence determinants beyond the
      polybasic hemagglutinin cleavage site.
AB  - Highly pathogenic avian influenza viruses (HPAIV) originate from avirulent
      precursors but differ from all other influenza viruses by the presence of a
      polybasic cleavage site in their hemagglutinins (HA) of subtype H5 or H7. In this
      study, we investigated the ability of a low-pathogenic avian H5N1 strain to
      transform into an HPAIV. Using reverse genetics, we replaced the monobasic HA
      cleavage site of the low-pathogenic strain A/Teal/Germany/Wv632/2005 (H5N1)
      (TG05) by a polybasic motif from an HPAIV (TG05(poly)). To elucidate the
      virulence potential of all viral genes of HPAIV, we generated two reassortants
      carrying the HA from the HPAIV A/Swan/Germany/R65/06 (H5N1) (R65) plus the
      remaining genes from TG05 (TG05-HA(R65)) or in reversed composition the mutated
      TG05 HA plus the R65 genes (R65-HA(TG05poly)). In vitro, TG05(poly) and both
      reassortants were able to replicate without the addition of trypsin, which is
      characteristic for HPAIV. Moreover, in contrast to avirulent TG05, the variants
      TG05(poly), TG05-HA(R65), and R65-HA(TG05poly) are pathogenic in chicken to an
      increasing degree. Whereas the HA cleavage site mutant TG05(poly) led to
      temporary non-lethal disease in all animals, the reassortant TG05-HA(R65) caused
      death in 3 of 10 animals. Furthermore, the reassortant R65-HA(TG05poly) displayed
      the highest lethality as 8 of 10 chickens died, resembling "natural" HPAIV
      strains. Taken together, acquisition of a polybasic HA cleavage site is only one
      necessary step for evolution of low-pathogenic H5N1 strains into HPAIV. However,
      these low-pathogenic strains may already have cryptic virulence potential.
      Moreover, besides the polybasic cleavage site, the additional virulence
      determinants of H5N1 HPAIV are located within the HA itself and in other viral
      proteins.

PMID- 20676400
TI  - HIV antigen incorporation within adenovirus hexon hypervariable 2 for a novel HIV
      vaccine approach.
AB  - Adenoviral (Ad) vectors have been used for a variety of vaccine applications
      including cancer and infectious diseases. Traditionally, Ad-based vaccines are
      designed to express antigens through transgene expression of a given antigen.
      However, in some cases these conventional Ad-based vaccines have had sub-optimal
      clinical results. These sub-optimal results are attributed in part to pre
      existing Ad serotype 5 (Ad5) immunity. In order to circumvent the need for
      antigen expression via transgene incorporation, the "antigen capsid
      incorporation" strategy has been developed and used for Ad-based vaccine
      development in the context of a few diseases. This strategy embodies the
      incorporation of antigenic peptides within the capsid structure of viral vectors.
      The major capsid protein hexon has been utilized for these capsid incorporation
      strategies due to hexon's natural role in the generation of anti-Ad immune
      response and its numerical representation within the Ad virion. Using this
      strategy, we have developed the means to incorporate heterologous peptide
      epitopes specifically within the major surface-exposed domains of the Ad capsid
      protein hexon. Our study herein focuses on generation of multivalent vaccine
      vectors presenting HIV antigens within the Ad capsid protein hexon, as well as
      expressing an HIV antigen as a transgene. These novel vectors utilize HVR2 as an
      incorporation site for a twenty-four amino acid region of the HIV membrane
      proximal ectodomain region (MPER), derived from HIV glycoprotein gp41 (gp41). Our
      study herein illustrates that our multivalent anti-HIV vectors elicit a cellular
      anti-HIV response. Furthermore, vaccinations with these vectors, which present
      HIV antigens at HVR2, elicit a HIV epitope-specific humoral immune response.

PMID- 20676401
TI  - Exposure to GSM RF fields does not affect calcium homeostasis in human
      endothelial cells, rat pheocromocytoma cells or rat hippocampal neurons.
AB  - In the course of modern daily life, individuals are exposed to numerous sources
      of electromagnetic radiation that are not present in the natural environment. The
      strength of the electromagnetic fields from sources such as hairdryers, computer
      display units and other electrical devices is modest. However, in many home and
      office environments, individuals can experience perpetual exposure to an
      "electromagnetic smog", with occasional peaks of relatively high electromagnetic
      field intensity. This has led to concerns that such radiation can affect health.
      In particular, emissions from mobile phones or mobile phone masts have been
      invoked as a potential source of pathological electromagnetic radiation. Previous
      reports have suggested that cellular calcium (Ca2+) homeostasis is affected by
      the types of radiofrequency fields emitted by mobile phones. In the present
      study, we used a high-throughput imaging platform to monitor putative changes in
      cellular Ca2+ during exposure of cells to 900 MHz GSM fields of differing power
      (specific absorption rate 0.012-2 W/Kg), thus mimicking the type of radiation
      emitted by current mobile phone handsets. Data from cells experiencing the 900
      Mhz GSM fields were compared with data obtained from paired experiments using
      continuous wave fields or no field. We employed three cell types (human
      endothelial cells, PC-12 neuroblastoma and primary hippocampal neurons) that have
      previously been suggested to be sensitive to radiofrequency fields. Experiments
      were designed to examine putative effects of radiofrequency fields on resting
      Ca2+, in addition to Ca2+ signals evoked by an InsP(3)-generating agonist.
      Furthermore, we examined putative effects of radiofrequency field exposure on
      Ca2+ store emptying and store-operated Ca2+ entry following application of the
      Ca2+ATPase inhibitor thapsigargin. Multiple parameters (e.g., peak amplitude,
      integrated Ca2+ signal, recovery rates) were analysed to explore potential impact
      of radiofrequency field exposure on Ca2+ signals. Our data indicate that 900 MHz
      GSM fields do not affect either basal Ca2+ homeostasis or provoked Ca2+ signals.
      Even at the highest field strengths applied, which exceed typical phone exposure
      levels, we did not observe any changes in cellular Ca2+ signals. We conclude that
      under the conditions employed in our experiments, and using a highly-sensitive
      assay, we could not detect any consequence of RF exposure.

PMID- 20676402
TI  - Oxidative stress and mitochondrial functions in the intestinal Caco-2/15 cell
      line.
AB  - BACKGROUND: Although mitochondrial dysfunction and oxidative stress are central
      mechanisms in various pathological conditions, they have not been extensively
      studied in the gastrointestinal tract, which is known to be constantly exposed to
      luminal oxidants from ingested foods. Key among these is the simultaneous
      consumption of iron salts and ascorbic acid, which can cause oxidative damage to
      biomolecules. METHODOLOGY/PRINCIPAL FINDINGS: The objective of the present work
      was to evaluate how iron-ascorbate (FE/ASC)-mediated lipid peroxidation affects
      mitochondrion functioning in Caco-2/15 cells. Our results show that treatment of
      Caco-2/15 cells with FE/ASC (0.2 mM/2 mM) (1) increased malondialdehyde levels
      assessed by HPLC; (2) reduced ATP production noted by luminescence assay; (3)
      provoked dysregulation of mitochondrial calcium homeostasis as evidenced by
      confocal fluorescence microscopy; (4) upregulated the protein expression of
      cytochrome C and apoptotic inducing factor, indicating exaggerated apoptosis; (5)
      affected mitochondrial respiratory chain complexes I, II, III and IV; (6)
      elicited mtDNA lesions as illustrated by the raised levels of 8-OHdG; (7) lowered
      DNA glycosylase, one of the first lines of defense against 8-OHdG mutagenicity;
      and (8) altered the gene expression and protein mass of mitochondrial
      transcription factors (mtTFA, mtTFB1, mtTFB2) without any effects on RNA
      Polymerase. The presence of the powerful antioxidant BHT (50 microM) prevented
      the occurrence of oxidative stress and most of the mitochondrial abnormalities.
      CONCLUSIONS/SIGNIFICANCE: Collectively, our findings indicate that acute exposure
      of Caco-2/15 cells to FE/ASC-catalyzed peroxidation produces harmful effects on
      mitochondrial functions and DNA integrity, which are abrogated by the powerful
      exogenous BHT antioxidant. Functional derangements of mitochondria may have
      implications in oxidative stress-related disorders such as inflammatory bowel
      diseases.

PMID- 20676403
TI  - A new approach for the discovery of antibiotics by targeting non-multiplying
      bacteria: a novel topical antibiotic for staphylococcal infections.
AB  - In a clinical infection, multiplying and non-multiplying bacteria co-exist.
      Antibiotics kill multiplying bacteria, but they are very inefficient at killing
      non-multipliers which leads to slow or partial death of the total target
      population of microbes in an infected tissue. This prolongs the duration of
      therapy, increases the emergence of resistance and so contributes to the short
      life span of antibiotics after they reach the market. Targeting non-multiplying
      bacteria from the onset of an antibiotic development program is a new concept.
      This paper describes the proof of principle for this concept, which has resulted
      in the development of the first antibiotic using this approach. The antibiotic,
      called HT61, is a small quinolone-derived compound with a molecular mass of about
      400 Daltons, and is active against non-multiplying bacteria, including
      methicillin sensitive and resistant, as well as Panton-Valentine leukocidin
      carrying Staphylococcus aureus. It also kills mupirocin resistant MRSA. The
      mechanism of action of the drug is depolarisation of the cell membrane and
      destruction of the cell wall. The speed of kill is within two hours. In
      comparison to the conventional antibiotics, HT61 kills non-multiplying cells more
      effectively, 6 logs versus less than one log for major marketed antibiotics. HT61
      kills methicillin sensitive and resistant S. aureus in the murine skin bacterial
      colonization and infection models. No resistant phenotype was produced during 50
      serial cultures over a one year period. The antibiotic caused no adverse affects
      after application to the skin of minipigs. Targeting non-multiplying bacteria
      using this method should be able to yield many new classes of antibiotic. These
      antibiotics may be able to reduce the rate of emergence of resistance, shorten
      the duration of therapy, and reduce relapse rates.

PMID- 20676404
TI  - Synaptotoxicity of Alzheimer beta amyloid can be explained by its membrane
      perforating property.
AB  - The mechanisms that induce Alzheimer's disease (AD) are largely unknown thereby
      deterring the development of disease-modifying therapies. One working hypothesis
      of AD is that Abeta excess disrupts membranes causing pore formation leading to
      alterations in ionic homeostasis. However, it is largely unknown if this also
      occurs in native brain neuronal membranes. Here we show that similar to other
      pore forming toxins, Abeta induces perforation of neuronal membranes causing an
      increase in membrane conductance, intracellular calcium and ethidium bromide
      influx. These data reveal that the target of Abeta is not another membrane
      protein, but that Abeta itself is the cellular target thereby explaining the
      failure of current therapies to interfere with the course of AD. We propose that
      this novel effect of Abeta could be useful for the discovery of anti AD drugs
      capable of blocking these "Abeta perforates". In addition, we demonstrate that
      peptides that block Abeta neurotoxicity also slow or prevent the membrane
      perforating action of Abeta.

PMID- 20676405
TI  - Extracellular and mixotrophic symbiosis in the whale-fall mussel Adipicola
      pacifica: a trend in evolution from extra- to intracellular symbiosis.
AB  - BACKGROUND: Deep-sea mussels harboring chemoautotrophic symbionts from
      hydrothermal vents and seeps are assumed to have evolved from shallow-water
      asymbiotic relatives by way of biogenic reducing environments such as sunken wood
      and whale falls. Such symbiotic associations have been well characterized in
      mussels collected from vents, seeps and sunken wood but in only a few from whale
      falls. METHODOLOGY/PRINCIPAL FINDING: Here we report symbioses in the gill
      tissues of two mussels, Adipicola crypta and Adipicola pacifica, collected from
      whale-falls on the continental shelf in the northwestern Pacific. The molecular,
      morphological and stable isotopic characteristics of bacterial symbionts were
      analyzed. A single phylotype of thioautotrophic bacteria was found in A. crypta
      gill tissue and two distinct phylotypes of bacteria (referred to as Symbiont A
      and Symbiont C) in A. pacifica. Symbiont A and the A. crypta symbiont were
      affiliated with thioautotrophic symbionts of bathymodiolin mussels from deep-sea
      reducing environments, while Symbiont C was closely related to free-living
      heterotrophic bacteria. The symbionts in A. crypta were intracellular within
      epithelial cells of the apical region of the gills and were extracellular in A.
      pacifica. No spatial partitioning was observed between the two phylotypes in A.
      pacifica in fluorescence in situ hybridization experiments. Stable isotopic
      analyses of carbon and sulfur indicated the chemoautotrophic nature of A. crypta
      and mixotrophic nature of A. pacifica. Molecular phylogenetic analyses of the
      host mussels showed that A. crypta constituted a monophyletic clade with other
      intracellular symbiotic (endosymbiotic) mussels and that A. pacifica was the
      sister group of all endosymbiotic mussels. CONCLUSIONS/SIGNIFICANCE: These
      results strongly suggest that the symbiosis in A. pacifica is at an earlier stage
      in evolution than other endosymbiotic mussels. Whale falls and other modern
      biogenic reducing environments may act as refugia for primal chemoautotrophic
      symbioses between eukaryotes and prokaryotes since the extinction of ancient
      large marine vertebrates.

PMID- 20676406
TI  - A landscape and climate data logistic model of tsetse distribution in Kenya.
AB  - BACKGROUND: Trypanosoma spp, biologically transmitted by the tsetse fly in
      Africa, are a major cause of illness resulting in both high morbidity and
      mortality among humans, cattle, wild ungulates, and other species. However,
      tsetse fly distributions change rapidly due to environmental changes, and fine
      scale distribution maps are few. Due to data scarcity, most presence/absence
      estimates in Kenya prior to 2000 are a combination of local reports,
      entomological knowledge, and topographic information. The availability of tsetse
      fly abundance data are limited, or at least have not been collected into
      aggregate, publicly available national datasets. Despite this limitation, other
      avenues exist for estimating tsetse distributions including remotely sensed data,
      climate information, and statistical tools. METHODOLOGY/PRINCIPAL FINDINGS: Here
      we present a logistic regression model of tsetse abundance. The goal of this
      model is to estimate the distribution of tsetse fly in Kenya in the year 2000,
      and to provide a method by which to anticipate their future distribution.
      Multiple predictor variables were tested for significance and for predictive
      power; ultimately, a parsimonious subset of variables was identified and used to
      construct the regression model with the 1973 tsetse map. These data were
      validated against year 2000 Food and Agriculture Organization (FAO) estimates.
      Mapcurves Goodness-Of-Fit scores were used to evaluate the modeled fly
      distribution against FAO estimates and against 1973 presence/absence data, each
      driven by appropriate climate data. CONCLUSIONS/SIGNIFICANCE: Logistic regression
      can be effectively used to produce a model that projects fly abundance under
      elevated greenhouse gas scenarios. This model identifies potential areas for
      tsetse abandonment and expansion.

PMID- 20676409
TI  - Synthetic collagen mimics: self-assembly of homotrimers, heterotrimers and higher
      order structures.
AB  - Collagen is a fascinating system of proteins that undergo a multi-step,
      hierarchical self-assembly which starts from individual peptide chains that
      assemble into a canonical triple helix. These triple helices then assemble into
      higher order structures which are often, but not always, fibrous in nature. While
      collagen is the most abundant protein in the human body, the details of its
      structure and mechanism of assembly are surprisingly poorly understood. This
      critical review will focus on small peptide systems, commonly referred to as
      collagen mimetic peptides (CMPs) which have been used successfully to help
      unravel some of the mystery of this complex structure. We will discuss
      homotrimeric CMPs, which are the most commonly researched subject in this field,
      and the structure of the collagen triple helix in detail and the factors that
      contribute to its stabilization. We will also cover how CMPs have been used to
      study breaks in triple helical domains as models for connective tissue diseases
      and, finally, how they have been used to understand the interactions of
      collagenous proteins with cell-surface receptors. Additionally, we will focus on
      heterotrimeric CMPs, a relatively new area of collagen research. Finally, we will
      deal with CMPs used as models for higher level self-assembly and also as
      materials that are designed to mimic the function of collagens in the
      extracellular matrix (178 references).

PMID- 20676407
TI  - HSV usurps eukaryotic initiation factor 3 subunit M for viral protein
      translation: novel prevention target.
AB  - Prevention of genital herpes is a global health priority. B5, a recently
      identified ubiquitous human protein, was proposed as a candidate HSV entry
      receptor. The current studies explored its role in HSV infection. Viral plaque
      formation was reduced by approximately 90% in human cells transfected with small
      interfering RNA targeting B5 or nectin-1, an established entry receptor. However,
      the mechanisms were distinct. Silencing of nectin-1 prevented intracellular
      delivery of viral capsids, nuclear transport of a viral tegument protein, and
      release of calcium stores required for entry. In contrast, B5 silencing had no
      effect on these markers of entry, but inhibited viral protein translation.
      Specifically, viral immediate early genes, ICP0 and ICP4, were transcribed,
      polyadenylated and transported from the nucleus to the cytoplasm, but the viral
      transcripts did not associate with ribosomes or polysomes in B5-silenced cells.
      In contrast, immediate early gene viral transcripts were detected in polysome
      fractions isolated from control cells. These findings are consistent with
      sequencing studies demonstrating that B5 is eukaryotic initiation factor 3
      subunit m (eIF3m). Although B5 silencing altered the polysome profile of cells,
      silencing had little effect on cellular RNA or protein expression and was not
      cytotoxic, suggesting that this subunit is not essential for host cellular
      protein synthesis. Together these results demonstrate that B5 plays a major role
      in the initiation of HSV protein translation and could provide a novel target for
      strategies to prevent primary and recurrent herpetic disease.

PMID- 20676410
TI  - Visualization and measurement of flow in two-dimensional paper networks.
AB  - The two-dimensional paper network (2DPN) is a versatile new microfluidic format
      for performing complex chemical processes. For chemical detection, for example,
      2DPNs have the potential to exceed the capabilities and performance of existing
      paper-based lateral flow devices at a comparable cost and ease of use. To design
      such 2DPNs, it is necessary to predict 2D flow patterns and velocities within
      them, but because of the scattering of the paper matrix, conventional particle
      imaging velocimetry is not practical. In this note, we demonstrate two methods
      for visualization of flow in 2DPNs that are inexpensive, easy to implement, and
      quantifiable.

PMID- 20676411
TI  - Rapid detection of viral RNA by a pocket-size real-time PCR system.
AB  - We present an economical, battery-powered real-time polymerase chain reaction (RT
      PCR) system suitable for field and point-of-care applications; it has a built-in
      thermal management, a fluorescence-based detection system, and a single chip
      controller with a graphic touch-screen display.

PMID- 20676412
TI  - Next-generation peptide nanomaterials: molecular networks, interfaces and
      supramolecular functionality.
AB  - With improved understanding of the design rules for self-assembling peptides, new
      challenges will be faced to incorporate these materials into dynamic systems of
      higher complexity and functionality. In this highlight article we discuss very
      recent advances in these areas. Three areas are covered: (i) molecular networks
      based on peptides and their interactions including (bio-) catalytically driven
      systems; (ii) supramolecular functionality, both in the context of biological and
      nanotechnology applications; (iii) approaches to effectively interface peptides
      with synthetic and biological materials. We also discuss challenges and
      opportunities for the design of a new generation of peptide nanomaterials for the
      next decade.

PMID- 20676413
TI  - Link between the hydration enthalpy of lysozyme and the density of its hydration
      water: Electrostriction.
AB  - Hydration shells around proteins in solution are on average denser than bulk
      water. Variations in enthalpy are observed during hydration/dehydration of
      proteins. To explain consistently those phenomena, a common mechanism
      electrostriction-underlying the mechanical and contributing to thermal effects is
      proposed. The mean mass density of the hydration shell of lysozyme derived from
      the neutron and X-ray scattering is explained as following the compression of
      water in the fields of the order of 10(9) V m(-1) due to the charged sites at the
      boundary of the protein. The mean enthalpy of mixing DeltaH(mean) of lysozyme in
      water calculated on the basis of the measured mean mass density falls in the
      middle of the values of the enthalpy of mixing DeltaH(mix) observed in sorption
      experiments. This testifies that DeltaH(mix) is due in part to the work done by
      the electrostriction pressure in hydration shell regions situated in high
      electric fields. The dependence of the sorption enthalpy of exemplary proteins on
      the number of adsorbed H(2)O molecules is also described in terms of
      electrostriction.

PMID- 20676414
TI  - A first principles study of fluorescence quenching in rhodamine B dimers: how can
      quenching occur in dimeric species?
AB  - Rhodamine B (RhB) is widely used in chemistry and biology due to its high
      fluorescence quantum yield. In high concentrations, the quantum yield of
      fluorescence decreases considerably which is attributed to the formation of RhB
      dimers. In the present work, a possible mechanism of fluorescence quenching in
      RhB dimers is investigated with the use of time-dependent density functional
      theory (TD-DFT). The excited states of monomeric and dimeric RhB species have
      been studied both in the gas phase and in solution with the use of the TD-BLYP/6
      311G* method. Results of the calculations suggest that quenching can occur via an
      internal conversion to the charge-transfer singlet excited states, which can be
      followed by an intersystem crossing with the charge-transfer triplet states. A
      possibility to reduce the loss of the fluorescence quantum yield is discussed.

PMID- 20676415
TI  - The OH stretch vibration of liquid water reveals hydrogen-bond clusters.
AB  - Using molecular dynamics simulations, we investigate the fluctuations of the
      hydrogen-bond network in liquid water and its relation to vibrational
      spectroscopy. We show that the high-frequency shoulder, which is most evidently
      found in Raman spectra of the OH stretch vibration of isotope diluted water, is
      (at least to a certain extent) related to a three-fold hydrogen-bonded ring. This
      suggests that it is not always sufficient to classify individual water molecules
      when studying some aspects of hydrogen-bond dynamics, rather, one should consider
      the topology of the local structure around a given water molecule.

PMID- 20676416
TI  - Metal mediated C-S rupture of heterocyclic thioamides: in situ generation of 2,2'
      thio-di-2-imidazoline, 1,1'-dimethyl-2,2'-di-imidazolylsulfide, SO4(2-) and their
      variable coordination to Cu(II).
AB  - Reactions of copper(I) halides with imidazolidine-2-thione and 1-methyl-1,3
      imidazoline-2-thione in dmso involved C-S rupture in aerobic conditions and
      yielded a sulfate bridged polymer, [Cu(II){eta(2)-N,N-(N(2)C(3)H(5))(2)S}(mu
      O,OSO(2))(eta(1)-OH(2))](n) 1 and a sulfate chelated monomer, [Cu(II){eta(2)-N,N
      (N(2)C(4)H(5))(2)S}(eta(2)-O,OSO(2))(eta(1)-OH(2))] 2 {N,N-(N(2)C(3)H(5))(2)S =
      2,2'-thio-di-2-imidazoline, N,N-(N(2)C(4)H(5))(2)S = 1,1'-dimethyl-2,2'-di
      imidazolyl sulfide}. This variable coordination behavior of in situ generated
      sulfate is unprecedented in the literature.

PMID- 20676417
TI  - BTP-based ligands and their complexes with Eu(3+) at "oil"/water interfaces. A
      molecular dynamics study.
AB  - Heterocyclic N-donor ligands based on the bistriazinylpyridine (BTPs) skeleton
      have been recently developed to separate trivalent actinides from lanthanides by
      liquid-liquid extraction from nuclear solutions. In this paper, we report
      molecular dynamics investigations on BTPs in water-"oil" biphasic systems (oil =
      hexane + octanol vs. hexane vs. nitrobenzene vs. chloroform) and compare
      different BTP derivatives, their neutral vs. protonated forms, and their 1 : 3
      complexes with Eu((III)). Neutral BTPs are found to be weakly surface active and
      to display multiple orientations at the interface, depending on time and on their
      lateral and para substituents. This contrasts with their protonated forms that
      strongly adsorb at interfaces with neutral or acidic water. Remarkably, the
      protonated cyMe(4)-BTPH(+) and, to a lesser extent, (i)PrBTPH(+) ligands adopts
      at the interface an "inversed orientation", where NH(+) points towards oil,
      instead of water. The [Eu(BTP)(3)](3+) complexes are also found to be highly
      surface active: in spite of Eu((III)) shielding by the three ligands, these
      complexes remain strongly attracted by water at the aqueous side of the
      interface. Taken together, the MD results suggest that ion complexation by BTPs
      occurs right at the interface, from the protonated BTPH(+) forms. They may
      explain why extraction is improved upon increase of the aqueous phase acidity,
      though with slow kinetics. They also open perspectives for designing new
      derivatives for efficient separation of trivalent actinides from lanthanides.

PMID- 20676418
TI  - Targeting glycolysis: a fragment based approach towards bifunctional inhibitors
      of hLDH-5.
AB  - hLDH-5 has emerged as a promising target for anti-glycolytic cancer chemotherapy.
      Here we report a first generation of bifunctional inhibitors, which show
      promising activity against hLDH-5.

PMID- 20676419
TI  - Nanoparticle-modified electrodes.
AB  - The behaviour of nanoparticle-modified electrodes is compared and contrasted with
      that of conventional unmodified macroelectrodes.

PMID- 20676420
TI  - Engineering biofunctional magnetic nanoparticles for biotechnological
      applications.
AB  - Synthesis and characterization of magnetic nanoparticles with excellent size
      control are showed here. Their functionalization using an amphiphilic polymer is
      also described. This strategy allows the stabilization of magnetic nanoparticles
      in aqueous solvents and in addition, the polymer shell serves as a platform to
      incorporate relevant biomolecules, such as poly(ethylene glycol) and a number of
      carbohydrates. Nanoparticles functionalized with carbohydrates show the ability
      to avoid unspecific interactions between proteins present in the working medium
      and the nanoparticles, so can be used as an alternative to poly(ethylene glycol)
      molecules. Results confirm these nanoparticles as excellent contrast agents for
      magnetic resonance imaging. Changes in the spin-spin transversal relaxation times
      of the surrounding water protons due to nanoparticle aggregation demonstrates the
      bioactivity of these nanoparticles functionalized with carbohydrates. To finish
      with, nanoparticle toxicity is evaluated by means of MTT assay. The obtained
      results clearly indicate that these nanoparticles are excellent candidates for
      their further application in nanomedicine or nanobiotechnology.

PMID- 20676421
TI  - Subunit exchange rates in Hepatitis B virus capsids are geometry- and temperature
      dependent.
AB  - Native tandem mass spectrometry reveals marked differences in the rates at which
      the two polymorphic forms of the HBV capsid exchange dimeric subunits with the
      soluble pool.

PMID- 20676423
TI  - A method for patterned in situ biofunctionalization in injection-molded
      microfluidic devices.
AB  - We developed a method to modify the surface in injection molded polymer
      microdevices prior to bonding and to pattern biomolecules in the completed
      microsystem in situ by a sequence of simple perfusion steps directly before
      utilization of the device. This method is compatible with production technology
      such as injection molding and bonding processes currently employed in the
      fabrication of polymer microsystems. It solves the problem of the inherent
      incompatibility of biomolecules with microfabrication technology as it allows for
      the biofunctionalization step to be performed after completion of the
      microsystem. Injection molded cyclic olefin copolymer (COC) microfluidic chips
      were modified by irradiating the surface with UV-light at lambda = 185 nm. This
      results in the formation of stable acidic groups which were further modified by
      binding of the extracellular matrix protein collagen type I. Non-irradiated
      surfaces were modified by binding of Pluronic(r) F-127 to become non-adhesive.
      Density of acid groups decreases to 50% within 45 days and to 25% within 19 weeks
      after irradiation. However, even then the remaining density of functional groups
      was shown to be sufficient to bind proteins and promote cell adhesion. Selective
      adhesion of primary hepatocytes on surfaces patterned by UV-irradiation and a
      biofunctional coating with collagen type I were demonstrated in injection molded
      microsystems.

PMID- 20676422
TI  - Maternal and fetal tissue accumulation of selected endocrine disrupting compounds
      (EDCs) following exposure to sewage sludge-treated pastures before or after
      conception.
AB  - Liver concentrations of selected pollutant classes were determined in groups of
      sheep fetuses and their dams, at 55 (Experiment 1) and 110 (Experiment 2) days of
      gestation (term = 145 d) following exposure, throughout their breeding lives and
      after mating, to pasture treated with either inorganic fertiliser (control, CC)
      or with sewage sludge (treated, TT). In a unique study designed to separate the
      respective contributions of environmental sources and mobilised tissue to the
      available EDC burden, in additional groups of animals, pollutant burdens at 110
      days gestation were assessed following exposure to the respective treatments,
      either throughout their breeding lives until mating, but not thereafter (TC), or
      only between mating and slaughter (CT) (Experiment 3). With very few exceptions,
      maternal and fetal liver concentrations of diethylhexyl phthalate (DEHP) and
      selected polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers
      (PBDE) and polycyclic aromatic hydrocarbons (PAHs) were not significantly
      affected by sludge exposure in any group. In some cases, maternal and fetal
      tissue EDC concentrations were different but the differences were not consistent,
      and maternal and fetal concentrations of none of the classes of chemical were
      significantly correlated. It was not possible to identify a single chemical, or
      class of chemical, that may be responsible for previously observed physiological
      effects of exposure to sludge-treated pastures. It is concluded that exposure of
      sheep to pastures fertilised with sewage sludge was not associated with increased
      liver concentrations of EDCs, irrespective of the stage of development at which
      they were measured and of maternal tissue mobilisation and EDC release during
      gestation. Thus, retrospective measurements of EDC tissue burdens could not be
      used to accurately assess earlier fetal EDC insults.

PMID- 20676424
TI  - Modification at a boron unit: tuning electronic and optical properties of pi
      conjugated acyclic anion receptors.
AB  - Substituents at the boron unit of dipyrrolyldiketone boron complexes as pi
      conjugated acyclic anion receptors play crucial roles for the tuning of solid
      state molecular assemblies, anion-binding behaviour and electronic and optical
      properties. In particular, emission quantum yields can be significantly tunable
      by boron substituents and pyrrole alpha-aryl moieties.

PMID- 20676425
TI  - Automatic, sequential power generation for prolonging the net lifetime of a
      miniature biofuel cell stack.
AB  - A sequential power generation system for prolonging the net lifetime of a
      miniature biofuel cell stack has been developed. The system consists of layered
      chambers of enzyme fuel cells designed to be exposed sequentially to fuel
      solution by automatically switched fuel flow. The cell chambers were initially
      separated by magnetized plastic covers sealed with a degradable glue, poly(lactic
      co-glycolic acid) (PLGA). The time that the cover was opened by attraction with
      an external magnet, thereby activating the following cell, was adjustable from a
      few hours to a few weeks by controlling the weight ratio of Fe(3)O(4) in the
      covers and the molecular weight of PLGA. By using sequential power generation in
      this way, the power output of the system was stable for longer periods, and
      therefore the net lifetime of the stack has been extended as compared with that
      of a single biofuel cell.

PMID- 20676426
TI  - A highly sensitive, selective, colorimetric and near-infrared fluorescent turn-on
      chemosensor for Cu2+ based on BODIPY.
AB  - A new colorimetric and NIR fluorescent chemosensor (1) for Cu(2+) based on BODIPY
      is reported, displaying a highly sensitive and selective fluorescent enhancement
      with Cu(2+) among various metal ions, upon excitation at 620 nm in CH(3)CN.

PMID- 20676427
TI  - Design and characterization of a sequential cyclone system for the collection of
      bulk particulate matter.
AB  - In this paper, we describe the design, development and characterization of a high
      volume sequential cyclone system for the collection of size-segregated PM in dry
      bulk form from the ambient environment in sufficient quantity for physical,
      chemical and toxicological characterization. The first stage of the system
      consists of a commercially available high volume PM(10) inlet. The second stage
      cyclone was designed by us to collect inhalable coarse particles (<10 um and >2.5
      um). When tested individually with a challenge aerosol, a D(50) cut-size of this
      stage was found to be 2.3 um at a flow rate of 1 m(3) min(-1). The third stage, a
      commercially available cyclone designed for surface dust sampling, had a D(50)
      cut-size of 0.3 um when tested at the same flow rate. The purpose of the third
      stage is to collect the fine particle portion of PM(2.5) or accumulation mode (PM
      <2.5 um and >0.1 um). Thus, the sequential cyclone system will collect bulk
      samples of both the inhalable coarse particles and the fine particle portion of
      PM(2.5). The operation and maintenance of the new system are straightforward and
      allow for reliable collection of dry bulk ambient PM at relatively low cost.

PMID- 20676428
TI  - Combined sulfating and non-sulfating support to prevent water and sulfur
      poisoning of Pd catalysts for methane combustion.
AB  - The appropriate combination of titania and silica, sulfating and non-sulfating
      support, respectively, results in Pd catalysts with improved water and sulfur
      tolerance in methane combustion. For the first time the catalyst recovers the
      initial activity after one cycle under lean-burn conditions without additional
      regenerating treatments.

PMID- 20676429
TI  - Calix[4]pyrrole-based anion transporters with tuneable transport properties.
AB  - Three new bis-1,2,3-triazole strapped calix[4]pyrroles have been prepared
      via'click' chemistry and their anion complexation and lipid bilayer transport
      properties studied by a combination of single crystal X-ray diffraction studies,
      (1)H NMR titration techniques, isothermal titration calorimetry and lipid bilayer
      anion transport studies in POPC vesicles. Bilayer transport efficiency for
      transmembrane chloride transport was found to directly depend on the length of
      the alkyl chain present in the bis-triazole strap.

PMID- 20676430
TI  - Coiled coils: attractive protein folding motifs for the fabrication of self
      assembled, responsive and bioactive materials.
AB  - The coiled coil is a superhelical protein structural motif that consists of two
      or more alpha-helical peptides that are wrapped around each other in superhelical
      fashion. Coiled coils are amongst the most ubiquitous folding motifs found in
      proteins and have not only been identified in structural proteins but also play
      an important role in various intracellular regulation processes as well as
      membrane fusion. The aim of this critical review is to highlight the potential of
      coiled coil peptide sequences for the development of self-assembled, responsive
      and/or bioactive materials. After a short historical overview outlining the
      discovery of this protein folding motif, the article will briefly discuss
      naturally occurring coiled coils. After that, the basic rules, which have been
      established to date for the design of coiled coils will be briefly summarized
      followed by a presentation of several classes of coiled coils, which may
      represent interesting candidates for the development of novel self-assembled,
      responsive and/or bioactive materials. This critical review will end with a
      section that summarizes the different coiled coil based (hybrid) materials that
      have been reported to date and which hopefully will help to stimulate further
      work to explore the full potential of this unique class of protein folding motifs
      for the development of novel self-assembled, responsive and/or bioactive
      materials (212 references).

PMID- 20676431
TI  - Characterisation of the membrane affinity of an isoniazide peptide conjugate by
      tensiometry, atomic force microscopy and sum-frequency vibrational spectroscopy,
      using a phospholipid Langmuir monolayer model.
AB  - Tensiometry, sum-frequency vibrational spectroscopy, and atomic force microscopy
      were employed to assess the cell penetration ability of a peptide conjugate of
      the antituberculotic agent isoniazide. Isoniazide was conjugated to peptide
      (91)SEFAYGSFVRTVSLPV(106), a functional T-cell epitope of the immunodominant 16
      kDa protein of Mycobacterium tuberculosis. As a simple but versatile model of the
      cell membrane a phospholipid Langmuir monolayer at the liquid/air interface was
      used. Changes induced in the structure of the phospholipid monolayer by injection
      of the peptide conjugate into the subphase were followed by tensiometry and sum
      frequency vibrational spectroscopy. The drug penetrated lipid films were
      transferred to a solid support by the Langmuir-Blodgett technique, and their
      structures were characterized by atomic force microscopy. Peptide conjugation was
      found to strongly enhance the cell penetration ability of isoniazide.

PMID- 20676432
TI  - Structure and stability of aluminium doped lithium clusters (Li(n)Al(0/+), n = 1
      8): a case of the phenomenological shell model.
AB  - Quantum chemical calculations are performed on the aluminium doped lithium
      clusters Li(n)Al at both neutral and cationic states using the DFT/B3LYP and
      CCSD(T) methods in conjugation with the aug-cc-pVaZ (a = D,T,Q) basis sets. The
      global minima are located and the growth mechanism is established. The electronic
      structure, geometrical parameters and energetic properties, such as average
      binding energy E(b), second difference of energy Delta(2)E, adiabatic and
      vertical ionization energy, and dissociated enthalpy, are evaluated using the
      coupled-cluster CCSD(T) method, whose energies are extrapolated to the complete
      basis set limit (CBS). The high stability of Li(5)Al, Li(7)Al, Li(6)Al(+) and
      Li(8)Al(+) that have the "magic numbers" of valence electrons, can be understood
      using the phenomenological shell model.

PMID- 20676433
TI  - In situ infrared (FTIR) study of the mechanism of the borohydride oxidation
      reaction.
AB  - Early reports stated that Au was a catalyst of choice for the BOR because it
      would yield a near complete faradaic efficiency. However, it has recently been
      suggested that gold could yield to some extent the heterogeneous hydrolysis of
      BH, therefore lowering the electron count per BH, especially at low potential.
      Actually, the blur will exist regarding the BOR mechanism on Au as long as no
      physical proof regarding the reaction intermediates is not put forward. In that
      frame, in situ physical techniques like FTIR exhibit some interest to study the
      BOR. Consequently, in situ infrared reflectance spectroscopy measurements (SPAIRS
      technique) have been performed in 1 M NaOH/1 M NaBH(4) on a gold electrode with
      the aim to detect the intermediate species. We monitored several bands in B-H (nu
      ~ 1180, 1080 and 972 cm(-1)) and B-O bond regions (nu = 1325 and ~1425 cm(-1)),
      which appear sequentially as a function of the electrode polarization. These
      absorption bands are assigned to BH(3), BH(2) and BO species. At the light of the
      experimental results, possible initial elementary steps of the BOR on gold
      electrode have been proposed and discussed according to the relevant literature
      data.

PMID- 20676434
TI  - Monitoring impedance changes associated with motility and mitosis of a single
      cell.
AB  - We present a device enabling impedance measurements that probe the motility and
      mitosis of a single adherent cell in a controlled way. The micrometre-sized
      electrodes are designed for adhesion of an isolated cell and enhanced sensitivity
      to cell motion. The electrode surface is switched electro-chemically to favour
      cell adhesion, and single cells are attracted to the electrode using positive
      dielectrophoresis. Periods of linear variation in impedance with time correspond
      to the motility of a single cell adherent to the surface estimated at 0.6 MUm h(
      1). In the course of our study we observed the impedance changes associated with
      mitosis of a single cell. Electrical measurements, carried out concomitantly with
      optical observations, revealed three phases, prophase, metaphase and anaphase in
      the time variation of the impedance during cell division. Maximal impedance was
      observed at metaphase with a 20% increase of the impedance. We argue that at
      mitosis, the changes detected were due to the charge density distribution at the
      cell surface. Our data demonstrate subtle electrical changes associated with cell
      motility and for the first time with division at the single-cell level. We
      speculate that this could open up new avenues for characterizing healthy and
      pathological cells.

PMID- 20676435
TI  - Calculation of local spins for correlated wave functions.
AB  - The recent formula for decomposing the expectation value <S(2)> of the total spin
      operator for general (correlated) wave functions has been rewritten in terms of
      the cumulant and is realized numerically for the first time. The results confirm
      its conformity with the physical expectations.

PMID- 20676436
TI  - A positively charged QDs-based FRET probe for micrococcal nuclease detection.
AB  - A new strategy for quantitatively detecting micrococcal nuclease (MNase) is
      proposed using electrostatic interaction-based fluorescence resonance energy
      transfer (FRET) between positively charged QDs and negatively charged dye-labeled
      single-stranded DNA (dye-ssDNA). Herein, we have made our attempt to develop a
      strategy where the variation of FRET efficiency is due to the change of the
      electrostatic interaction between QDs and the ssDNA that result from the cleavage
      of dye-ssDNA by a single-strand-specific nuclease. To demonstrate the feasibility
      of this design, positively charged QDs (lysozyme modified QDs, Lyz-QDs) are
      prepared as the energy donor, with the fluorescent dye 6-carboxy-X-rhodamine
      (ROX) that is labeled to ssDNA serving as the energy acceptor. The ROX-labeled
      probe ssDNA (ROX-ssDNA) is absorbed to the surface of the QDs through
      electrostatic interaction, which results in resonance energy transfer between the
      QDs and the dye. In the presence of MNase which cleaves the ROX-ssDNA into small
      fragments, the weakened interaction between QDs and the shortened ssDNA causes
      the decrease of FRET efficiency. At given amounts of donor and acceptor, the
      ratio of fluorescence intensity of QDs to ROX changes in a MNase concentration
      dependent manner. Under optimized conditions, the ratio is linear with MNase
      concentration over the range of 8 x 10(-3) to 9.0 x 10(-2) unit mL(-1), with a
      limit of detection of 1.6 x 10(-3) unit mL(-1). This new detection strategy
      features straightforward design and easy operation, which is capable of expanding
      the application of the positively charged QDs-based FRET in DNA-related
      bioassays.

PMID- 20676437
TI  - Viable route for switching of an engineered silica surface using Cu2+ ions at sub
      ppm levels.
AB  - Quartz substrates were functionalized with a covalent 4-ClCH(2)C(6)H(4)SiCl(3)
      monolayer. To this, N-(4-hydroxyphenethyl)-4,5-di[(2-picolyl)amino]-1,8
      naphthalimide molecules were then covalently bonded, producing a new monolayer of
      these molecules on silica substrates. The surface chemical characterization of
      this hybrid material was carried out by X-ray photoelectron spectroscopy. The
      switching properties of this monolayer were studied at room temperature by UV-vis
      and XPS measurements. The system has reversible recognition properties for Cu(2+)
      ions at sub-ppm levels and, therefore, can be reversibly switched using Cu ions
      as input and the absorbance intensity as output between two states represented by
      the free base and its copper complex. The adopted synthetic procedure has proven
      effective to transfer molecular properties to a solid state device.

PMID- 20676438
TI  - Stereoselective Ir(III)-catalyzed dimerization reaction of enynes: an entry to
      functionalized polyunsaturated and cyclic systems.
AB  - The Ir(III) complex [Ir(2)H(2)I(3)((rac)-Binap)(2)](+)I(-) efficiently promotes
      the selective dimerization of 1,6-, 1,7-enynes and functionalized alkynes. This
      catalytic process results in the formation of head-to-head isomers with (E)
      stereoselectivity. Subsequent Rh-catalyzed cycloisomerization under reductive
      conditions led to the corresponding 1,2-dialkylidenecyclopentane derivatives.

PMID- 20676440
TI  - Mechanistic insight into NOYORI asymmetric hydrogenations.
AB  - The BINAP-Ru-catalyzed asymmetric hydrogenations have contributed fundamentally
      to "molecular catalyst chemistry", as well as the "chemical industry", in terms
      of the production of important chiral compounds such as pharmaceuticals,
      agrochemicals, flavors, fragrances, and health supplements since 1986 when the
      great breakthrough was made through an efficient asymmetric synthesis of
      tetrahydroisoquinolines. This highlight overviews mechanistic models proposed in
      the Noyori hydrogenation of olefins and ketones.

PMID- 20676439
TI  - Structural insights into substrate specificity and solvent tolerance in alcohol
      dehydrogenase ADH-'A' from Rhodococcus ruber DSM 44541.
AB  - The structure of the alcohol dehydrogenase ADH-'A' from Rhodococcus ruber reveals
      possible reasons for its remarkable tolerance to organic co-solvents and suggests
      new directions for structure-informed mutagenesis to produce enzymes of altered
      substrate specificity or improved selectivity.

PMID- 20676441
TI  - A porous LiFePO4 and carbon nanotube composite.
AB  - A novel composite electrode structure with highly-conductive 3D nanotube networks
      superimposed into interlaced porous LiFePO(4) media was designed and realized via
      an in situ sol-gel process, yielding a high-performance multidimensional
      composite cathode for high-energy and high-power lithium-ion batteries.

PMID- 20676442
TI  - Folding dynamics of a small protein at room temperature via simulated coherent
      two-dimensional infrared spectroscopy.
AB  - Understanding protein folding is of fundamental and practical importance in
      chemistry and biology. Despite the great success that has been made in tackling
      this problem, a detailed knowledge of how the elementary processes such as
      hydrogen-bond formation occur during protein folding has remained largely
      elusive. Using the combined power of molecular dynamics simulation with
      electrostatic polarization and coherent two-dimensional infrared spectroscopy, we
      are able to delineate the order of the hydrogen-bond formation event of a 17
      residue peptide during its folding from an extended state to the native alpha
      helix state. The folding is carried out by a single trajectory room-temperature
      molecular dynamics simulation that includes the polarization effect of hydrogen
      bonding, which is critical to the successful folding of the peptide. The onset
      and evolution of the isotope-labeled amide I vibration diagonal and cross peaks
      on the simulated 2DIR spectra allow us to build a structure-spectrum connection,
      and thus provide a microscopic picture of the helix folding process.

PMID- 20676443
TI  - More than just bare scaffolds: towards multi-component and decorated fibrous
      biomaterials.
AB  - We are entering a new phase in biomaterials research in which rational design is
      being used to produce functionalised materials tailored to specific applications.
      As is evident from this Themed Issue, there are now a number of distinct types of
      designed, self-assembling, fibrous biomaterials. Many of these are ripe for
      development and application for example as scaffolds for 3D cell culture and
      tissue engineering, and in templating inorganic materials. Whilst a number of
      groups are making headway towards such applications, there is a general challenge
      to translate a wealth of excellent basic research into materials with a genuine
      future in real-life applications. Amongst other contemporary aspects of this
      evolving research area, a key issue is that of decorating or functionalising what
      are mostly bare scaffolds. There are a number of hurdles to overcome to achieve
      effective and controlled labelling of the scaffolds, for instance: maintaining
      biocompatibility, i.e., by minimising covalent chemistry, or using milder
      bioconjugation methods; attaining specified levels of decoration, and, in
      particular, high and stoichiometric labelling; introducing orthogonality, such
      that two or more functions can be appended to the same scaffold; and, in relevant
      cases, maintaining the possibility for recombinant peptide/protein production. In
      this critical review, we present an overview of the different approaches to
      tackling these challenges largely for self-assembled, peptide-based fibrous
      systems. We review the field as it stands by placing work within general routes
      to fibre functionalisation; give worked examples on our own specific system, the
      SAFs; and explore the potential for future developments in the area. Our feeling
      is that by tackling the challenges of designing multi-component and functional
      biomaterials, as a community we stand to learn a great deal about self-assembling
      biomolecular systems more broadly, as well as, hopefully, delivering new
      materials that will be truly useful in biotechnology and biomedical applications
      (107 references).

PMID- 20676444
TI  - Directional decisions during neutrophil chemotaxis inside bifurcating channels.
AB  - The directional migration of human neutrophils in classical chemotaxis assays is
      often described as a "biased random walk" implying significant randomness in
      speed and directionality. However, these experiments are inconsistent with in
      vivo observations, where neutrophils can navigate effectively through complex
      tissue microenvironments towards their targets. Here, we demonstrate a novel
      biomimetic assay for neutrophil chemotaxis using enclosed microfluidic channels.
      Remarkably, under these enclosed conditions, neutrophils recapitulate the highly
      robust and efficient navigation observed in vivo. In straight channels,
      neutrophils undergo sustained, unidirectional motion towards a chemoattractant
      source. In more complex maze-like geometries, neutrophils are able to select the
      most direct route over 90% of the time. Finally, at symmetric bifurcations,
      neutrophils split their leading edge into two sections and a "tug of war" ensues.
      The competition between the two new leading edges is ultimately resolved by
      stochastic, symmetry-breaking behavior. This behavior is suggestive of
      directional decision-making localized at the leading edge and a signaling role
      played by the cellular cytoskeleton.

PMID- 20676445
TI  - A solid-state NMR and DFT study of compositional modulations in Al(x)Ga(1-x)As.
AB  - We have conducted (75)As and (69)Ga Nuclear Magnetic Resonance (NMR) experiments
      to investigate order/disorder in Al(x)Ga(1-x)As lift-off films with x~ 0.297 and
      0.489. We were able to identify all possible As(Al(n)Ga(4-n)) sites with n = 0-4
      coordinations in (75)As NMR spectra using spin-echo experiments at 18.8 Tesla.
      This was achieved by employing high rf field strengths using a small solenoid
      coil and an NMR probe specifically designed for this purpose. Spectral
      deconvolution, using an evolutionary algorithm, complies with the absence of long
      range order if a CuAu based order parameter is imposed. An unconstrained fit
      shows a deviation of the statistics imposed by this type of ordering. The
      occupational disorder in the Ga and Al positions is reflected in a distribution
      of the Electric Field Gradients (EFGs) experienced at the different arsenic
      sites. We established that this can be modelled by summing the effects of the
      first coordination sphere and a Czjzek type distribution resulting from the
      compositional variation in the Al/Ga sub-lattice in the higher coordination
      spheres. (69)Ga 3QMAS and nutation data exclude the presence of highly symmetric
      sites and also show a distribution in EFG. The experimentally obtained
      quadrupolar interactions are in good agreement with calculations based on Density
      Functional Theory (DFT). Using additivity of EFG tensors arising from distant
      charge perturbations, we could use DFT to model the EFG distributions of the n =
      0-4 sites, reproducing the Czjzek and extended Czjzek distributions that were
      found experimentally. On the basis of these calculations we conclude that the
      (75)As quadrupolar interaction is sensitive to compositional modulations up to
      the 7th coordination shell in these systems.

PMID- 20676446
TI  - An octacobalt cluster based, (3,12)-connected, magnetic, porous coordination
      polymer.
AB  - Solvothermal reaction of CoSO(4) with 2,6-di-p-carboxyphenyl-4,4'-bipyridine
      affords a novel, octacobalt cluster based, (3,12)-connected porous framework,
      which exhibits gas sorption and spin-glassy magnetic behaviour.

PMID- 20676447
TI  - Surface functionalisation of diatoms with dopamine modified iron-oxide
      nanoparticles: toward magnetically guided drug microcarriers with biologically
      derived morphologies.
AB  - Diatom silica microcapsules prepared by purification of diatomaceous earth (DE)
      were functionalised by dopamine modified iron-oxide nanoparticles, in order to
      introduce diatoms with magnetic properties. The application of magnetised diatoms
      as magnetically guided drug delivery microcarriers has been demonstrated.

PMID- 20676448
TI  - Absorption spectroscopy of adenine, 9-methyladenine, and 2-aminopurine in helium
      nanodroplets.
AB  - High-resolution absorption spectra of adenine, 9-methyladenine and 2-aminopurine
      in helium nanodroplets have been recorded. In contrast to molecular beam
      experiments, large variations in linewidths are observed for adenine and 9
      methyladenine. At the same time, the spectrum of 2-aminopurine remains sharp upon
      solvation in helium droplets. The line broadening observed for adenine and 9
      methyladenine is attributed to a significant decrease of the lifetime of the
      (1)L(b)(pipi*) state and of (1)npi* levels vibronically coupled to this state.
      The origin of the lifetime reduction is argued to be related to the increased
      accessibility of the (1)npi*/(1)L(b)(pipi*) conical intersection upon solvation
      of these molecules in liquid helium.

PMID- 20676449
TI  - Impact of modification of carbon black on morphology and performance of
      polyimide/carbon black hybrid composites.
AB  - The composite films based on polyimide (PI) and chloride modified carbon black
      (CB-COCl) were prepared by conversion of biphenyltetracarboxylic dianhydride and
      4,4'-oxydianiline in the presence of CB-COCl, followed by thermal imidization.
      The presence of chemical bonds between PI and CB-COCl, proved by FTIR spectra of
      the composites, has a considerable effect on the properties of PI films. Scanning
      electron microscopy (SEM) pictures of the PI/CB-COCl membranes showed changed
      morphology compared to reference membranes without CB-COCl. The thermal stability
      and structure of the composites were studied by differential scanning calorimetry
      (DSC), thermogravimetric analyses (TGA) and X-ray diffraction (XRD),
      respectively. These hybrid films showed an increase in thermal decomposition
      temperature and a slightly enhanced glass transition temperature. On their
      mechanical properties, the modulus and ultimate strength of the hybrid films
      increased and elongation at break decreased with increased CB-COCl content. The
      surface free energy of polyimide films were determined by means of the contact
      angle measurements.

PMID- 20676450
TI  - Ruthenium complexes with chiral tetradentate PNNP ligands: asymmetric catalysis
      from the viewpoint of inorganic chemistry.
AB  - This is a personal account of the application of ruthenium complexes containing
      chiral tetradentate ligands with a P(2)N(2) ligand set (PNNP) as catalyst
      precursors for enantioselective "atom transfer" reactions. Therewith are meant
      reactions that involve bond formation between a metal-coordinated molecule and a
      free reagent. The reactive fragment (e.g. carbene) is transferred either from the
      metal to the non-coordinated substrate (e.g. olefin) or from the free reagent
      (e.g. F(+)) to the metal-bound substrate (e.g.beta-ketoester), depending on the
      class of catalyst (monocationic, Class A; or dicationic, Class B). The
      monocationic five-coordinate species [RuCl(PNNP)](+) and the six-coordinate
      complexes [RuCl(L)(PNNP)](+) (L = Et(2)O, H(2)O) of Class A catalyse asymmetric
      epoxidation, cyclopropanation (carbene transfer from the metal to the free
      olefin), and imine aziridination. Alternatively, the dicationic complexes [Ru(L
      L)(PNNP)](2+) (Class B), which contain substrates that act as neutral bidentate
      ligands L-L (e.g., beta-ketoesters), catalyse Michael addition, electrophilic
      fluorination, and hydroxylation reactions. Additionally, unsaturated beta
      ketoesters form dicationic complexes of Class B that catalyse Diels-Alder
      reactions with acyclic dienes to produce tetrahydro-1-indanones and estrone
      derivatives. Excellent enantioselectivity has been achieved in several of the
      catalytic reactions mentioned above. The study of key reaction intermediates
      (both in the solid state and in solution) has revealed significant mechanistic
      aspects of the catalytic reactions.

PMID- 20676451
TI  - On the origin of copper(I) catalysts from copper(II) precursors in C-N and C-O
      cross-couplings.
AB  - Cu(II) precursors ligated to phenanthrolines are reduced in situ by alcohols or
      amines in the presence of a base (Cs(2)CO(3)) to generate Cu(I) species which are
      active catalysts in C-N and C-O cross-coupling reactions. The conversion Cu(II) -
      > Cu(I) has been evidenced and monitored by UV-vis and NMR spectroscopy.

PMID- 20676452
TI  - Effect of proteins on the synthesis and assembly of calcium phosphate
      nanomaterials.
AB  - Recent developments on biomineralization and biomaterials have demonstrated that
      proteins play an important role in the formation of biominerals in the body,
      which induce or inhibit mineralization of calcium phosphate together with
      modulation of the mineral phase structure. Many efforts have been made to
      understand the mechanism of this process and mimic the exquisite structure of
      biominerals in biomimetic methodologies. This review is focused on recent
      advances in the synthesis of calcium phosphate materials by taking advantage of
      protein assemblies. We try to review the examples of templates based on proteins
      and polypeptides that have been successfully employed to manufacture calcium
      phosphate nanomaterials.

PMID- 20676453
TI  - Dynamics study of the atmospheric reaction involving vibrationally excited O(3)
      with OH.
AB  - We investigate the title atmospheric reaction of highly excited O(3) with
      vibrationally cold OH. Particular attention will be paid to initial vibrational
      energies of O(3) between 9 and 21 kcal mol(-1). The calculations employ the
      quasiclassical trajectory method and the realistic double many-body expansion
      potential energy surface for HO(4)((2)A). Many aspects of the title process are
      presented. It is found that it may not be possible to ignore this process when
      studying the stratospheric ozone budget.

PMID- 20676454
TI  - New insights in the formation of silanol defects in silicalite-1 by water
      intrusion under high pressure.
AB  - The "water-silicalite-1" system is known to act as a molecular spring. The
      successive intrusion-extrusion cycles of liquid water in small crystallites (6 *
      3 * 0.5 MUm(3)) of hydrophobic silicalite-1 were studied by volumetric and
      calorimetric techniques. The experiments displayed a decrease of the intrusion
      pressure between the first intrusion-extrusion cycle and the consecutive ones,
      whereas the extrusion pressures remained unchanged. However, neither XRD studies
      nor SEM observations revealed any structural and morphological modifications of
      silicalite-1 at the long-range order. Such a shift in the value of the intrusion
      pressure after the first water intrusion-extrusion cycle is attributed to the
      creation of silanol groups during the first water intrusion. Detailed FTIR and
      solid-state NMR spectroscopic characterizations provided a molecular evidence of
      chemical modification of zeolite framework with the formation of local silanol
      defects created by the breaking of siloxane bonds.

PMID- 20676455
TI  - The catalytic effect of water on the keto-enol tautomerism. Pyruvate and
      acetylacetone: a computational challenge.
AB  - The catalytic effect of explicit water molecules on the keto-enol tautomerism in
      a system of biological interest (enolpyruvate) has been investigated at the
      B3LYP/6-31++G** level by exploring the potential energy surface in the presence
      of 1 or 2 water molecules and comparing the energy profiles to the direct
      tautomerisation one. The water-assisted mechanisms turned out to be more
      favourable than the direct ones, in agreement with what occurred for the
      acetylacetone tautomerism in the presence of a single water molecule. To compare
      the behaviour of water in pyruvate and in acetylacetone, the two-water-assisted
      mechanism has been also examined for the latter at the B3LYP/6-31G* level. A
      number of stationary points for both compounds in vacuo and in the presence of
      explicit water molecules have been computed with DFT coupled to larger basis sets
      and at the MP2 level. Two diketo forms more stable than any of the keto-enol
      tautomers have been located, while for pyruvate the keto form is always more
      favourable than the enol one. The equilibrium constant for acetylacetone
      tautomerisation has been computed with high accuracy, performing a complete basis
      set extrapolation for the relative internal energy, to determine whether the
      quality of the method/basis set is responsible for the earlier modest agreement
      with the experimental value. Monte Carlo and molecular dynamics simulations
      helped characterize the solution structure and association features in the 0.03
      0.22 molar concentration range.

PMID- 20676456
TI  - Lepidocrocite-like structure of the TiO(2) monolayer grown on Ag(100).
AB  - Titanium oxide ultrathin films were grown on Ag(100) by evaporation of titanium
      in an O(2) atmosphere. The growth of the oxide films was monitored by means of
      XPS. The Ti2p XPS spectra indicate the formation of films with a TiO(2)
      stoichiometry in the whole range of coverages studied here. The STM results show
      that titania films appear to grow as islands of uniform thickness up to the
      completion of the first layer. Up to the formation of one complete monolayer, a
      (5 * 1) LEED pattern is observed. This pattern can be interpreted as a
      coincidence mesh and the lattice parameters of the oxide layer are very close to
      those of TiO(2) films with a lepidocrocite-like structure. However, the STM
      images show a long-range coincidence between the periodicity of the oxide film
      and that of the substrate along the short side of the oxide unit cell revealing
      that this lattice parameter is not exactly equal to that of the substrate. Above
      the monolayer coverage, additional spots become visible in the LEED pattern which
      can be interpreted in terms of the unit cell of rutile (110). The structural
      determination was carried out for the monolayer of titania by means of XPD and
      LEED intensity analysis. The results of these investigations demonstrate that the
      titania monolayer has a lepidocrocite-like structure. The DFT calculations
      carried out for the titania monolayer show the higher stability of the
      lepidocrocite structure with respect to other structures derived from
      crystallographic planes of bulk TiO(2) phases. Moreover, these calculations allow
      us to determine the oxide-substrate interface energy as well as to clarify the
      effect of the strain on the stability of the oxide layer.

PMID- 20676457
TI  - Kinetic and thermochemical studies of the ClO + ClO + M <=> Cl(2)O(2) + M
      reaction.
AB  - Recent work by von Hobe et al. [Atmos. Chem. Phys., 2007, 7, 3055] has
      highlighted significant inconsistencies between laboratory results, theoretical
      calculations and field observations concerning the ClO dimer ozone destruction
      cycle. This work investigates the temperature dependence of the equilibrium
      constant of one of the key reactions in this cycle, ClO + ClO + M <=> Cl(2)O(2) +
      M (1, -1), by means of laser flash photolysis and time-resolved UV absorption
      spectroscopy. ClO radicals were generated via laser flash photolysis of
      Cl(2)/Cl(2)O mixtures in synthetic air. Radicals were monitored via UV absorption
      spectroscopy: the use of a charge coupled device (CCD) detector allowed time
      resolution over a broad range of wavelengths giving unequivocal concentrations of
      radicals. The equilibrium constant K(eq) was determined as the ratio of the rate
      constants of the forward and reverse over the temperature range T = 256.55-312.65
      K. Second Law and Third Law thermodynamic methods were employed to determine the
      standard enthalpy and entropy changes of , Delta(r)H degrees  and Delta(r)S
      degrees , from the measured equilibrium constants. The values obtained from
      Second Law analysis were Delta(r)H degrees  = - 80.7 +/- 2.2 kJ mol(-1) and
      Delta(r)S degrees  = -168.1 +/- 7.8 J K(-1) mol(-1). Third Law analysis gave
      Delta(r)H degrees  = -74.65 +/- 0.4 kJ mol(-1) and Delta(r)S degrees  = -148.0 +/
      0.4 J K(-1) mol(-1). These values are in good agreement with previous work by
      Nickolaisen et al. [J. Phys. Chem., 1994, 98, 155] but greater in (negative)
      magnitude than current JPL-NASA recommendations [Sander et al., Chemical Kinetics
      and Photochemical Data for Use in Atmospheric Studies, JPL Publication 06-2, NASA
      Jet Propulsion Laboratory, Pasadena, 2006 (interim update to this reference,
      2009)]. The discrepancy between the Second and Third Law analyses also agrees
      with Nickolaisen et al., possibly indicating an aspect of the ClO recombination
      reaction not yet fully elucidated. The atmospheric implications of the results
      and their impact on the current understanding on polar ozone depletion are
      briefly discussed.

PMID- 20676458
TI  - Optical detection of heterogeneous single molecule diffusion in thin liquid
      crystal films.
AB  - Lateral diffusion of three different dye molecules (terrylene and two perylene
      diimides) in 4 to 225 nm thin films of 8CB liquid crystals in the smectic-A phase
      has been investigated on a single molecule level. The influence of film thickness
      on tracer diffusion can be qualitatively modeled by a hydrodynamic approach.
      Molecular tracking experiments as well as fluorescence correlation (FCS) studies
      reveal the presence of diffusion dynamics which span a range of at least more
      than one order of magnitude in time, which is much larger than the reported
      anisotropic self-diffusion observed for 8CB bulk samples. We tentatively assign
      the heterogeneity to the formation of diffusion limiting domains on a micrometer
      scale within the 8CB films or at the interfaces.

PMID- 20676459
TI  - Optical and electronic properties of native zinc oxide films on polycrystalline
      Zn.
AB  - The oxide layer spontaneously formed on zinc and an "electrochemically reduced"
      oxide has been characterised by a combination of X-ray photoelectron spectroscopy
      (XPS) and spectroscopic ellipsometry (SE). The onset of the main electronic
      absorption, which is directly related to the bandgap, is extracted from the SE
      measurements. The SE results are compared with simulations on the basis of zinc
      and bulk zinc oxide optical constant data. Measurements in the ultraviolet and
      visible (UV-vis) spectral range show the presence of an absorption at ~1.8 eV
      (680 nm) which is unaccounted for from the bulk data, and is likely to originate
      from intragap energy levels, implicating the presence of surface defects in the
      layers. Analysis of the Zn LMM Auger peaks in XPS data show the presence of Zn
      different from bulk zinc and bulk ZnO, attributed to excess Zn in the oxide
      films. Mid-infrared (IR) ellipsometry shows two peaks around 0.12 and 0.15 eV
      (1000 and 1200 cm(-1)), which strengthen the assumption of the presence of a
      locally distorted structure in the oxide layers. Electrochemically reduced
      samples show a much thinner oxide layer and higher Zn-doping concentration films
      than samples purely dipped in NaOH solution. Using a self-contained multiple
      sample SE analysis, estimates of the refractive index and absorption coefficient
      (i.e., the optical constants) of the oxide films are presented from 1.5-4.4 eV
      (280 to 810 nm).

PMID- 20676460
TI  - Sequential combination of Michael and acetalization reactions: direct catalytic
      asymmetric synthesis of functionalized 4-nitromethyl-chromans as drug
      intermediates.
AB  - Functionalized chiral 4-nitromethyl-chromans as drug intermediates were achieved
      for the first time through sequential combination of Michael and acetalization
      reactions on 2-(2-nitro-vinyl)-phenols with acetone and alcohols in the presence
      of a catalytic amount of 9-amino-9-deoxyepiquinine and Ph(2)CHCO(2)H followed by
      p-TSA.

PMID- 20676461
TI  - [IV Guidelines of Sociedade Brasileira de Cardiologia for Treatment of Acute
      Myocardial Infarction with ST-segment elevation].

PMID- 20676462
TI  - Buruli ulcer.
AB  - Buruli ulcer, an infectious disease caused by Mycobacterium ulcerans, is the
      third most prevalent mycobacteriosis, after tuberculosis and leprosy. This
      atypical mycobacteriosis has been reported in over 30 countries, mainly those
      with tropical and subtropical climates, but its epidemiology remains unclear. The
      first autochthonous cases of infection in Brazil have recently been described,
      making this diagnosis important for Brazilian dermatologists. Clinical
      manifestations vary from nodules, areas of edema, and plaques, but the most
      typical presentation is a large ulcer, usually in the limbs. Despite considerable
      knowledge about its clinical manifestations in some endemic countries, in other
      areas the diagnosis may be overlooked. Therefore, physicians should be educated
      about Buruli ulcer, since early diagnosis and treatment, including measures to
      prevent disability, are essential for a good outcome.

PMID- 20676463
TI  - Therapeutic management of skin hemangiomas in children.
AB  - BACKGROUND: Hemangiomas are benign, self-involuting tumors of endothelial cells
      that are common in childhood. OBJECTIVES: To evaluate the treatment of 122
      patients with skin hemangiomas treated at a teaching hospital in Brasilia, Brazil
      between March 2000 and December 2006. MATERIAL AND METHODS: Data were collected
      from the patients' medical records and questionnaires were applied to the
      children's parents. Variables analyzed were: gender, pre- and perinatal factors,
      clinical characteristics of the lesions, type of treatment and outcome. RESULTS:
      A male-to-female ratio of 1.5:1 was found. In 42 patients, hemangiomas were
      superficial, while in 13 cases they were deep and in 67 patients lesions were
      mixed. In 7 patients, the lesions were associated with syndromes. In 79 patients,
      hemangiomas were in the cephalic region. Of the 122 patients, 98 were submitted
      to one single treatment, while 24 required multiple forms of treatment. In the
      first group, expectant management was the conduct in 38 patients, compression in
      3 cases, systemic corticotherapy in 18 patients, intralesional corticotherapy in
      13, topical steroids in 4 cases, conventional surgery in 12 patients, cryosurgery
      in 7, pulsed light in one case and imiquimod in 2 patients. In the second group
      of 24 patients submitted to multiple treatment modalities, 15 required two types
      of treatment and 9 needed three or more. CONCLUSIONS: The data obtained in this
      study were in agreement with results in the literature with respect to gender and
      the site of the lesions. The incidence of hemangiomas present at birth was higher
      than rates published in the literature. The therapeutical results obtained were
      comparable with data from other published studies. Identification of hemangiomas
      that require treatment, as well as the right moment for intervention and the best
      therapeutic option for each case, are factors that need to be taken into
      consideration.

PMID- 20676464
TI  - Nail disorders in patients with chronic renal failure undergoing hemodialysis.
AB  - BACKGROUND: Chronic renal failure affects almost all the systems of the body,
      including the skin and appendages. The nail disorders most commonly found in
      patients with chronic renal failure are half and half nails, absent lunula and
      splinter hemorrhages. OBJECTIVES: To evaluate the spectrum and the frequency of
      nail disorders in patients with chronic renal failure submitted to hemodialysis
      and compare them with a paired sample from the general population. METHODS: A
      case-controlled study paired for gender and age was conducted in which nail
      disorders were investigated in the two groups. RESULTS: At least one nail
      disorder was found in 86% of the hemodialysis patients and in 75% of subjects in
      the control group. Absent lunula (62.9%) and half and half nails (14.4%) were
      more common in the hemodialysis group compared to the control group and this
      difference was statistically significant (p < 0.05). Longitudinal striae were
      more common in the control group compared to the hemodialysis group (24.1%).
      CONCLUSIONS: Absent lunula and half and half nails were the most common nail
      disorders found in patients on hemodialysis, corroborating the findings of
      previous studies. Longitudinal striae were more common in the control group and
      future studies may clarify whether structural abnormalities such as absent lunula
      may be related to this finding.

PMID- 20676465
TI  - Evaluation of the disk-diffusion method to determine the in vitro efficacy of
      terbinafine against subcutaneous and superficial mycoses agents.
AB  - BACKGROUND: Superficial and subcutaneous mycoses have a high prevalence and,
      often, chronic evolution. Therefore, they need extensive treatment with topic
      and/or systemic antifungal agents. Azoles and alilamines (terbinafine) are first
      choice drugs to treat human and animal infections. Thus, evaluation of the
      efficacy of these drugs is important for a successful treatment. However, there
      are few studies that evaluate the in vitro activity of antifungal agents.
      OBJECTIVE: To evaluate the in vitro efficacy of terbinafine activity against
      filamentous fungi and yeasts that cause mycoses. METHOD: The in vitro activity of
      terbinafine (0.125-100microg) against 10 fungi species was evaluated by the
      diskdiffusion and microdilution/reference methods to determine the Minimum
      Inhibitory Concentration (MIC). RESULTS: We found a high susceptibility to
      terbinafine in: T. rubrum, M. gypseum, T. mentagrophytes, T. tonsurans, M. canis,
      C. carrionii and E. floccosum (halo > or = 40mm with 0.125microg disk). S.
      hyalinum and C. parapsilosis were considered susceptible, but less than the
      others. Fusarium spp. showed the lowest susceptibility (halo=12mm with 2microg
      disk; MIC 8microg/mL). CONCLUSIONS: The results of this research confirm previous
      findings about the efficacy of terbinafine. The drug was shown to be highly
      effective to treat dermatophyte infections. The disk-diffusion method was easy to
      use and is a suitable technique for routine use in clinical laboratories.

PMID- 20676466
TI  - Evaluation of clinical adverse effects and laboratory alterations in patients
      with acne vulgaris treated with oral isotretinoin.
AB  - BACKGROUND: Oral isotretinoin therapy has completely changed the treatment of
      acne. The clinical adverse effects of isotretinoin are classified into two
      groups: mucocutaneous and systemic toxic. Laboratory alterations such as
      dyslipidemia and increase of hepatic enzymes are reported. OBJECTIVES: To
      evaluate the tolerability of oral isotretinoin with special attention to lipid
      metabolism, hepatic function, and clinical adverse reactions. METHODS: 150
      patients clinically diagnosed with acne being treated with oral isotretinoin were
      included in the study. Clinical and laboratory evaluations were conducted before
      the start of therapy, one month after, and every three months thereafter until
      the completion of treatment. RESULTS: Of the 150 patients evaluated, 48% were
      female and 52%, male. They were aged from 15 to 32 years. The most prevalent
      mucocutaneous adverse reaction associated with isotretinoin therapy was
      cheilitis, reported by 94% of the patients. Systemic clinical effects were much
      less common. Cholesterol, triglyceride, and transaminase levels were assessed and
      significant changes were not observed during treatment. CONCLUSION: Patients
      showed adverse effects compatible to those described in the literature, which are
      mostly controlled with symptomatic medication. Isotretinoin is a safe drug and
      adverse and laboratory effects are well tolerated.

PMID- 20676467
TI  - Epidemiologic study of 107 cases of families with leprosy in Duque de Caxias, Rio
      de Janeiro, Brazil.
AB  - BACKGROUNDS: ultibacillary patients are the major source of infection in leprosy.
      Nevertheless, the risk is higher in household contacts between multibacillary
      patients than paucibacillary patients and in the general population. Household
      contacts are in close genetic relationship with the index case-patient.
      OBJECTIVE: To evaluate epidemiological data of the following variables: age,
      gender, education level, genetic proximity, and type of contact with the index
      case-patient (household or not) in 107 families with leprosy. METHODS: Home
      visits were conducted to clinically examine family members. The medical charts of
      index case-patients and co-prevalent cases were reviewed. RESULTS: The controlled
      analysis of variables such as type of contact and genetic proximity revealed that
      household contacts and first-degree kinship are independently associated with a
      higher chance of contracting the disease. CONCLUSION: Household contacts are
      often genetically closer to the index case-patient. To investigate the
      independent relevance of these risks in leprosy surveillance contact studies has
      been a challenge. Our results confirm literature data that show the influence of
      genetics in the susceptibility to leprosy per se.

PMID- 20676468
TI  - Acne and diet: truth or myth?
AB  - Numerous studies were published over the last 50 years to investigate whether
      diet is associated with the etiology of acne. Although older studies well known
      by dermatologists that refute the association between acne and diet exist, their
      scientific foundation is weak. New articles have recently brought to light
      evidence contrary to previous findings. Therefore, we would like to investigate
      whether diet, directly or indirectly, influences one or more of the four
      fundamental etiopathogenic pillars of acne: (1) hyperproliferation of basal
      keratinocytes, (2) increase of sebaceous production, (3) colonization by
      Propionibacterium acnes, and (4) inflammation.

PMID- 20676469
TI  - Psoriasis and obesity: literature review and recommendations for management.
AB  - Recent studies have found a relationship between obesity and chronic
      inflammation, confirmed by the association of high levels of tumor necrosis
      factor (TNF-_), interleukin six (IL-6,) and reactive C-protein with an increase
      in body mass index (BMI). In obese individuals, this inflammatory condition could
      contribute to the development or aggravation of psoriasis. Analogous phenomena
      have already been described in other inflammatory chronic diseases, such as
      rheumatoid arthritis and Crohn's disease. Epidemiological studies have identified
      a high prevalence of cardiovascular comorbidities, secondary to the metabolic
      alterations associated with psoriasis and obesity. A few aspects of this
      association remain unclear, such as the impact of obesity in the clinical forms
      of dermatoses, in the response to treatment, and its relationship with
      comorbidities.

PMID- 20676470
TI  - Morphometric analysis of dermal collagen by color clusters segmentation.
AB  - Morphometric analysis of dermal collagen can provide quantitative support to
      dermatologic research. The authors of this article disclose a technique of
      digital image analysis which allows the identification of microscopic structures
      by color cluster segmentation regarding the estimate intensity and density of
      dermal collagen fibers.

PMID- 20676471
TI  - Paget's disease: the importance of the specialist.
AB  - A twenty-six-year-old woman with a two-year history of an erythematous, scaly
      lesion on the left nipple was being followed up by her gynecologist and treated
      using a topical corticoid for chronic eczema albeit with no improvement. She was
      referred to this department where a diagnosis of Paget's disease of the breast
      associated with a ductal carcinoma in situ was made. Paget's disease is uncommon
      prior to the fourth decade of life and the great majority of cases are associated
      with breast carcinomas. Differential diagnosis must be made between this
      condition and nipple eczema. As shown in the present case report, late diagnosis
      results in poor prognosis and higher morbidity since mutilating procedures then
      become necessary.

PMID- 20676472
TI  - Hidrocystoma: surgical management of cystic lesions of the eyelid.
AB  - This report describes the case of a hidrocystoma of the eyelid and the surgical
      technique used in the therapeutical management of benign cystic lesions of the
      eyelids. Hidrocystomas are relatively common benign lesions of the eyelids,
      principally the lower eyelid. They are more common in females over thirty years
      of age. Diagnosis is clinical and when there is a single lesion, surgery is the
      treatment of choice. The surgical technique used should be described in greater
      detail, since it offers good esthetic results and a low risk of recurrence.

PMID- 20676473
TI  - X-linked incontinentia pigmenti or Bloch-Sulzberger syndrome: a case report.
AB  - Incontinentia pigmenti is a rare X-linked genodermatosis that affects mainly
      female neonates. Skin manifestations are the most common and occur in four quite
      distinct phases. A female infant presented vesiculobullous lesions on trunk and
      limbs, and a verrucous lesion on the right palm. Biopsy revealed eosinophil
      exocytosis and pigment incontinence, confirming the clinical hypothesis. Although
      uncommon, incontinentia pigmenti should be taken into consideration as a possible
      differential diagnosis when vesiculobullous and verrucous lesions are present in
      childhood.

PMID- 20676474
TI  - Fatal outcome in classic Kaposi's sarcoma.
AB  - First described in 1872, Kaposi's sarcoma is defined as a rare multifocal tumor
      that originates in the endothelial cells and presents with cutaneous and
      extracutaneous manifestations. The classic form is most common in elderly men and
      progression is slow. This tumor responds well to chemotherapy and radiotherapy.
      This report describes a classic case of Kaposi's sarcoma in a woman with skin and
      visceral manifestations in whom the disease rapidly progressed to a fatal
      outcome.

PMID- 20676475
TI  - Becker nevus syndrome.
AB  - Becker nevus syndrome is a phenotype characterized by the fundamental presence of
      Becker's nevus with ipsilateral hypoplasia of the breast or other skin, skeletal
      and/or muscular disorders. This syndrome generally originates at birth,
      intensifies significantly in adolescence and is one of the syndromes that
      constitute epidermal nevus syndrome. To the best of our knowledge, this is the
      first case published in the Brazilian literature of Becker nevus syndrome
      associated with Becker's nevus, ipsilateral breast hypoplasia and scoliosis in a
      14-year-old girl.

PMID- 20676476
TI  - Melanocyte transplant in piebaldism: case report.
AB  - Piebaldism is a rare genodermatosis in which depigmented skin areas are
      unresponsive to topical or light treatment. This article describes the importance
      of transplant techniques using noncultured melanocytes (minigrafting) in the
      treatment of piebaldism.

PMID- 20676477
TI  - Ixodiasis disclosed by epiluminescence microscopy without skin contact.
AB  - We describe the case of a 48-year-old healthy man who sought for medical help in
      our clinic with multiple pruriginous erythematous papules after a 2-day trip to
      "Serra da Mantiqueira". (Mantiqueira Mountain). A meticulous physical exam with a
      portable epiluminescence microscopy showed several ticks on a larval form on the
      skin of the patient.

PMID- 20676478
TI  - Exogenous pigmentation in toes feigning ischemia of the extremities: a diagnostic
      challenge brought by arthropods of the Diplopoda Class ("millipedes").
AB  - A 24 year-old patient reported having stepped on a millipede. When examined the
      patient presented cyanotic and erythematous macules on the first three toes of
      his right foot, and also complained of local pain and paresthesia, with palpable
      arterial flows. Millipedes are cylindrical segmented arthropods that when
      threatened form into curls and release quinones and other irritant and pigmentary
      substances. The cyanotic color reminds ischaemic tissular distress fact that may
      confuse professionals in Emergency Rooms when the clinical report is unclear.

PMID- 20676479
TI  - Case for diagnosis. Idiopathic calcinosis.
AB  - Idiopathic calcinosis is a rare disease characterized by abnormal deposit of
      calcium salts on the dermis. It has several clinical presentations. In patients
      suffering from Down Syndrome, there is a rare association with idiopathic
      calcinosis lesions similar to milium.

PMID- 20676480
TI  - Case for diagnosis. Localized scleroderma or morphea.
AB  - Localized scleroderma or morphea is a chronic disease of the connective tissue.
      Its etiology may be autoimmune and the condition results from a disturbance in
      collagen synthesis and deposition, clinically represented by sclerotic skin
      lesions. Some plaques may be yellowish, which can be misleading at diagnosis.
      This article reports the case of an adolescent girl who concomitantly presented
      erythematous lesions and yellowish lesions, both of which constitute clinical
      manifestations of the disease.

PMID- 20676481
TI  - Cybertutor: a teaching tool in Dermatology.
AB  - It was developed a teaching tool in Dermatology for undergraduate medical
      students, using an interactive website, the Cybertutor. Clinical cases, lectures
      and updated bibliography were selected. Photographies of dermatological lesions
      were taken from ambulatory patients. The topics of the lectures were based on the
      current curriculum of the Federal University of Rio Grande do Sul. The Cybertutor
      is a dynamic and modern teaching tool, allowing constant innovation.

PMID- 20676482
TI  - Study about the association between anticardiolipin antibodies and peripheral
      vascular phenomena in patients suffering from systemic scleroderma.
AB  - Ischemia is common in systemic scleroderma and it is caused by vasospasm and
      thrombosis. In the present study we analyzed the association of peripheral
      vascular events and anticardiolipin (aCl) antibodies in 54 patients suffering
      from systemic scleroderma. The results showed that 100% of the patients presented
      Raynaud; 59.2% presented digital micro scars; 43.3%, presented teleangiectasies
      and 14.8%, presented peripheral thromboembolism. ACl IgG were positive in 9.2%
      and IgM, in 7.4%. Peripheral tromboembolic phenomena had a positive association
      with aCl IgG (p=0.03). No other associations were found.

PMID- 20676483
TI  - Papulosis mucinosis versus atypical tuberous myxedema of Dossekker.

PMID- 20676486
TI  - Alveolar osseous defect in rat for cell therapy: preliminary report.
AB  - PURPOSE: To study were to reproduce an alveolar bone defect model in Wistar rats
      to be used for testing the efficacy of stem cell therapies. Additionally, we also
      aimed to determine the osteogenesis process of this osseous defect in the 1 month
      period post-surgery. METHODS: The animals were randomly divided into two groups
      of 7 animals each. A gingivobuccal incision was made, and a bone defect of 28
      mm(2) of area was performed in the alveolar region. Animals were killed at 2
      weeks after surgery (n=7) and 4 weeks after surgery (n=7). RESULTS: The average
      area of the alveolar defect at time point of 2 weeks was 22.27 +/- 1.31 mm(2) and
      the average area of alveolar defect at time point of 4 weeks was 9.03 +/- 1.17
      mm(2). The average amount of bone formation at time point of 2 weeks was 5.73 +/-
      1.31 mm(2) and the average amount of bone formation at time point of 4 weeks was
      19 +/- 1.17 mm(2). Statistically significant differences between the amount of
      bone formation at 2 weeks and 4 weeks after surgery were seen (p=0.003).
      CONCLUSION: The highest rate of ossification occurred mostly from 2 to 4 weeks
      after surgery. This observation suggests that 4 weeks after the bone defect
      creation should be a satisfactory timing to assess the potential of bone
      inductive stem cells to accelerate bone regeneration in Wistar rats.

PMID- 20676487
TI  - Ischemia-reperfusion histopathology alterations of the rabbit intestinal wall
      with and without exclusion of the collateral mesenteric circulation supply.
AB  - PURPOSE: To evaluate the histopathology alterations of the intestinal mucosa of
      rabbits submitted to different times of mesenteric artery ischemia and
      reperfusion with and without celiac artery collateral circulation supply.
      METHODS: Two groups of eight male New Zealand white rabbits (weight 2.2-3.5 kg)
      were used in this study. In the Group 1 animals, the proximal mesenteric artery
      was occluded for 60 min with an atraumatic vascular clamp, followed by
      reperfusion for 60 min. In the Group 2 animals the small bowel and mesentery were
      cut 30cm and 60cm far from the gastroduodenal pyloric transition before the
      proximal mesenteric artery occlusion. Small bowel biopsies were obtained before
      ischemia (control), after 30 min and 60 min of mesenteric ischemia and at 30 and
      60 min. of mesenteric artery reperfusion. RESULTS: In the Group I animals, the
      followings histopathology grade results were observed: t1, mean 0.4 + 0.29; t2,
      mean 1.9 +/- 0.38; t3, 1.9 +/- 0.33; t4, 1.2 +/- 0.36 and t5, 1.2 +/- 0.32.
      Differences between t0 and t2 and between t3 and t4 were statistically
      significant (p<0.05). Differences between t2 and t3 and t4 and t5 were not
      significant (p>0.5). In the Group II animals, it was observed: t1, mean 1.6 +/-
      0.33; t2, 2.4 +/- 0.36; t3, 3.0 +/- 0.35; t4 3.4 +/- 0.31; t5, 3 +/- 031.
      Differences between t0 and t1, t1 and t2, and t2 and t3 were significant
      (p<0.05). Differences between histopathology grades results of samples t1 to t5
      in Group 1 and 2 were statistically significant (p<0.5). CONCLUSION: Microscopic
      examination of the biopsies revealed significant evidence of worse small bowel
      wall ischemia-reperfusion lesions by exclusion of the celiac artery collateral
      circulation supply.

PMID- 20676488
TI  - Effects of the povidone-iodine (PVPI) in treatment of bacterial peritonitis
      induced in rats.
AB  - PURPOSE: To evaluate the effectiveness of the use of the povidone-iodine (PVI)
      added to the liquid of wash of the peritoneal cavity in the reduction of
      bacterial absorption and in the remainder non-phagocyted bacteria in the
      circulating blood of rat. METHODS: Thirty four Wistar females rats were used,
      distributed in the following groups: A (n=10), non-treated; B (n=9), wash of the
      peritoneal cavity with solution of PVI to 1% in saline solution; C (n=15), wash
      of the cavity with saline solution. After anesthesia, it was made intraperitoneal
      infusion of solution of Escherichia coli labeled with 99mTc containing 10(8)
      CFU/ml. After 40 minutes, it was made the treatment, in the group A, manipulation
      of the viscera; in the group B, irrigation of the peritoneal cavity with warm
      solution of 1% PVPI to 37,5 degrees C, and in the group C irrigation with warm
      saline (37,5 degrees C). After 15 minutes of the treatment, blood samples and
      fragments of liver, spleen and lung was obtained for count of the radioactivity,
      and animals killed by abdominal aorta section. There were determined the
      bacterial absorption index and the remainder index in the bloodstream. RESULTS:
      Of the total of bacteria infused in the peritoneum, there was absorption of 0,92%
      (0,14% to 2,13%) in the animals of the group A (controls), 0,49% (0,18% to 0,71%)
      after use of topical PVPI (group B) and 0,80% (0,04% to 3,8%) after wash with
      saline solution (group C). There was significant reduction of the absorption when
      compared the treated animals with PVPI and the controls (p=0,003). Of the total
      of bacteria absorbed for the circulatory current, the percentile amount of
      bacteria non-phagocyted in the outlying blood was of 2,9% (1,1% to 17,7%) in the
      control group, 15,2% (8,3% to 21,4%) in those treated with PVPI (group B) and
      6,9% (0,8% to 29,7%) after wash with saline solution (group C), with difference
      among controls and treated with PVPI (p=0,01). CONCLUSION: The wash of the cavity
      peritoneal of mice with solution containing PVPI showed to be capable to reduce
      the absorption of bacteria by peritoneum of rat; however it seems to interfere
      with the function of the phagocytic cells for the observation of the increase of
      viable bacteria in the outlying blood of those animals.

PMID- 20676489
TI  - Proliferation and cell death in an experimental model of brain tissue heterotopia
      in the lung.
AB  - PURPOSE: To investigate the proliferation and neuronal death in brain tissue
      heterotopia in the lung in an experimental model during both fetal and neonatal
      periods. METHODS: Twenty four pregnant female Swiss mice were used to induce
      brain tissue heterotopia on the 15th gestational day. Briefly, the brain of one
      fetus of each dam was extracted, disaggregated and injected into the right
      hemithorax of siblings. Six of these fetuses with pulmonary brain tissue
      implantation (PBI) were collected on the 18th gestational day (group E18) and six
      other on the 8th postnatal day (group P8). Immunohistochemical staining for PCNA
      and Bcl2 were used to assess proliferation and cell death. RESULTS: PCNA
      Labelling Index (LI) in heterotopic brain tissue was greater in fetal than
      postnatal period (E18 > P8) (p<0.05) and the immunostaining with Bcl2 antibody
      did not show difference. CONCLUSION: Cell proliferation is maintained in brain
      tissue heterotopia, although apoptosis is also observed.

PMID- 20676490
TI  - Porcine peritoneum as source of biocompatible collagen in mice.
AB  - PURPOSE: To investigate the biocompatibility and biodegradability of a membrane
      made from porcine peritoneum. METHODS: The membrane (5x5 mm) was inserted in the
      subcutaneous tissue on the back of 15 mice, which were killed after 1, 3 and 9
      weeks (ISO 10993-6). The cellular components of the inflammatory response and
      degradation of the membrane were analyzed in hematoxylin-eosin-stained
      histological sections. RESULTS: After one week, mononuclear cells were observed
      inside the membrane. After three weeks, the material was almost completely
      absorbed. After nine weeks, there was no presence of material and there were
      signs of tissue remodeling. There was neither a foreign body reaction nor signs
      of tissue necrosis. CONCLUSION: The collagen membrane derived from porcine
      peritoneum is biocompatible and bioabsorbable when implanted in the subcutaneous
      tissue of mice.

PMID- 20676491
TI  - Evaluation of peritoneal adhesions formation and tissue response to polypropylene
      - poli (2-hydroxyethyl methacrylate)-(polyHEMA) implant on rats' abdominal wall.
AB  - PURPOSE: To verify if the composit poli (2-hydroxyethyl methacrylate)
      PolyHEMA/polypropylene mesh implanted in the female rat's abdominal wall could be
      suitable for the prevention of peritoneal adhesions, and for the evaluation of
      the tecidual response produced by this biomaterial. METHODS: Polypropylene meshes
      (Group PP, n=20) and polypropylene meshes coated with a layer of poli (2
      hydroxyethyl methacrylate)-PolyHEMA (Group PH, n=20) were implanted on the
      abdominal wall of Wistar female rats. Ten animals from each group were submitted
      to euthanasia at 15 and 30 days of the postoperative period. RESULTS: The animals
      from the group PP presented visceral adhesions on the mesh surface, which was not
      observed in the ones from group PH. At the histopathological examination foreign
      body response was observed in both groups, whilst there was a greater intensity
      of inflammatory response in group PH on both moments. CONCLUSION: The poli (2
      hydroxyethyl methacrylate) polyHEMA hydrogel associated to polypropylene mesh
      reduces visceral adhesion formation in rats, although it may be associated to
      greater inflammatory reaction.

PMID- 20676492
TI  - 2-hydroxyethyl methacrylate composite - polypropylene mesh for preventing
      peritoneal adhesions in female dogs.
AB  - PURPOSE: To evaluate whether the lining facing the visceral side of polypropylene
      mesh made with 2-hydroxyethyl methacrylate (p(HEMA)) hydrogel could avoid
      peritoneal adhesion in female dogs. METHODS: Eight animals (group PP) had a
      polypropylene mesh implanted to correct a defect in the rectal abdominal muscle,
      whereas in the other group (group PH) the polypropylene mesh was coated with
      p(HEMA) composite on the surface facing the peritoneal area. RESULTS: Adhesions
      were observed on the mesh in 62.5% of the PP group. In the PH group adhesions
      were present only on the suture lines. CONCLUSION: p(HEMA) hydrogel was well
      tolerated and effective in avoiding visceral and omental adhesions on the surface
      of the polypropylene mesh.

PMID- 20676493
TI  - Mapping traction strength of the anterior rectus sheath in cadaver.
AB  - PURPOSE: The tension at the aponeurotic edges of abdominal wall defects is an
      important factor of dehiscence and incisional hernia formation. The purpose of
      this study is to map and compare the traction force necessary for medial
      mobilization in various levels of the anterior rectus sheath in cadavers.
      METHODS: Twenty four adult male cadavers, raging from 22 to 59 years old, with
      the abdominal wall intact and without prior preservation techniques, were
      dissected. A complete excision of the linea alba was performed. Traction loops of
      10 mm in diameter were made in the anterior rectus sheath and were placed: 2, 4,
      6 and 8 cm below the lower edge of the umbilicus and 3, 6 and 9 cm above the
      upper edge of the umbilicus. Each loop was mobilized 10 mm in the medial
      direction, using an analog dynamometer. The values obtained in each level were
      compared using Friedman's analysis of Variance for p < 0.05. RESULTS: The average
      traction values obtained at the various levels were compared and there was no
      statistical significant difference. CONCLUSION: There is no variation in tension
      along the whole extension of the anterior rectus sheath.

PMID- 20676494
TI  - FT-Raman spectroscopy for the differentiation between cutaneous melanoma and
      pigmented nevus.
AB  - Cutaneous melanoma is the most aggressive type of skin cancer and Ft-Raman
      spectroscopy has been studied as a potential method that could be a real
      alternative for early diagnosis of neoplasms. PURPOSE: To qualify the spectral FT
      Raman data, in order to differentiate cutaneous melanoma and pigmented nevus.
      METHODS: For this study, 10 samples of cutaneous melanoma, 9 samples of pigmented
      nevi, and 10 samples of normal skin were obtained by incisional biopsies
      performed during plastic surgeries ex vivo, immediately after removing the
      surgical sample. RESULTS: The FT-Raman spectra of each group presented a high
      correlation between the elements of the same group, thus favoring the elaboration
      of spectral averages. When analyzing the spectral standard of each group, the
      normal skin standard did not show a significant variation between the spectra;
      the standard of the pigmented nevi group showed significant variation, and the
      cutaneous melanoma group also showed variation. Through univariate analysis,
      specific bands were detected for each vibrational mode identified. The
      discriminatory analysis of the data showed a 75.3% efficiency of the
      differentiation between the three groups studied. CONCLUSION: The vibrational
      modes Polysaccharides, Tyrosine and Amide-I differentiated the melanoma from the
      pigmented nevus.

PMID- 20676495
TI  - Dimethylsulfoxide attenuates ischemia-reperfusion injury in rat testis.
AB  - PURPOSE: To evaluate the protective role of dimethylsulfoxide (DMSO) in a rat
      model of testis ischemia/reperfusion (I/R). METHODS: Twenty-four male Wistar rats
      were randomized in two equal groups. Control rats (G-1) received saline 2.0 ml
      intraperitoneally (ip) 21, 9 and 1 h before torsion. Experimental rats (G-2)
      received ip injections of 3% aqueous solution of DMSO, 0.1ml/10g body weight.
      Saline was added to complete 2.0ml when necessary. I/R injury was induced in
      anesthetized rats by torsion of the right testis lasting 3 hours. Testis and
      blood samples were collected at the end of ischemia (T-0) and 3 hours later (T-3)
      for assessment of testis malonaldehyde (MDA), reduced glutathione (GSH), and
      plasma total antioxidant power (TAP). RESULTS: MDA levels decreased significantly
      in G-2 rats compared with G-1 animals in all time-points. GSH levels increased
      significantly in T-0 and T-3 time-points in DMSO pretreated rats compared with G
      1 rats. GSH levels increased significantly during reperfusion in G-2 rats. TAP
      was similar in both groups denoting absence of systemic effects in this study.
      CONCLUSION: Pretreatment with DMSO reduces testis lipid peroxidation and
      oxidative stress caused by torsion/detorsion of the testis.

PMID- 20676496
TI  - Rupture point analysis of intestinal anastomotic healing in rats under the action
      of pure Copaiba (Copaifera Iangsdorfii) oil.
AB  - PURPOSE: Analyze the mechanical strength of digestive tract scar after intestinal
      anastomosis surgery in animals treated with pure Copaiba oil. METHODS: 60 Wistar
      rats, male, about 250 days old and weighting around 350g were used. The rats were
      randomly divided into two groups: Group O, with 30 animals that received Copaiba
      oil and Group C, with 30 animals that received saline. Each group was subdivided
      into three subgroups, containing 10 rats each. They were designated O7, O14, O28,
      C7, C14 and C28, according to the post-operative assessment date at 7, 14 and 28
      days, respectively. On these dates euthanasia was performed with the removal of
      the bowel segment containing the anastomosis and assigning the samples to tensile
      test for assessing Maximum Stress, Maximum Tensile Strength and Maximum Rupture
      Strength. RESULTS: On the three variables of the study, the results indicate
      that, for the three assessment periods (7, 14 and 28 days) there was no
      significant difference between the oil and control groups. CONCLUSION: For the
      mechanical tests proposed by this study, Copaiba oil didn t show any
      effectiveness in increasing the anatomosis strength.

PMID- 20676497
TI  - Hyperbaric oxygen therapy and mechanical resistence of the colonics anastomosis
      in rats with peritonitis.
AB  - PURPOSE: To analyze the effects of hyperbaric oxygen therapy (HBO) on the
      mechanical resistance of anastomosis performed in rats' distal colon presenting
      peritonitis induced by ligature and cecal punction using the Total Energy Rupture
      biomechanical test (ETR). METHODS: It was used 45 rats divided into three groups
      of 15 animals each. In Control Group (CG), it was performed anastomosis in distal
      colon without peritonitis. In Peritonitis Group (PG), it was performed
      anastomosis six hours after the induction of peritonitis by ligature and cecal
      punction. In Hyperbaric Chamber Group (HCG), it was performed six hours after the
      induction of peritonitis by ligature and cecal punction. The animals on CG and PG
      were kept at place air while the animals on HCG were placed on an experimental
      hyperbaric chamber in order to inhale oxygen at 100%, two absolute atmospheres,
      for 120 minutes, for four consecutive days. Euthanasia took place on the fifth
      day of the experiment. All the animals underwent to Total Energy Rupture
      Biomechanical Resistance test (ETR). Total Energy Rupture was defined as the
      necessary internal energy stored up to promote the colon rupture after an
      external traction force imposition. RESULTS: The Peritonitis Group presents
      smaller average ETR than Control Group. There was no statistical difference
      between Peritonitis Group and Hyberbaric Chamber Group. CONCLUSION: Hyperbaric
      oxygen therapy did not alter the mechanical resistance of anastomosis performed
      in distal colon of rats under the presence of peritonitis induced by ligature and
      cecal puncture.

PMID- 20676498
TI  - Influence of glutamine on morphological and functional changes of liver in the
      presence of extrahepatic biliary obstruction in rats.
AB  - PURPOSE: To study the influence of glutamine on functional and morphological
      changes of liver in the extrahepatic biliary obstruction through an experimental
      model in rats. METHODS: Seventy Wistar rats were divided into four groups:
      control (group C) fictitious operation, (group FO), submitted to laparotomy with
      handling of bile ducts, but without hepatic duct ligation, (group EBO) submitted
      to laparotomy and hepatic duct ligation, one of them submitted to supplementation
      with glutamine 2% (group G). The control group consisted of 6 animals. The
      animals from groups FO, EBO and G were divided into three groups consisting of 6
      animals each, being sacrificed at 7, 14 and 21 days after operation,
      respectively. Blood samples were collected for biochemical analysis and a
      fragment of liver tissue was collected from the middle lobe for histological
      analysis. RESULTS: Both for biochemical analysis (BT, aspartate and alanine
      aminotransferase AST, ALT and alkaline phosphatase FAL) and for histopathological
      changes (fibrosis, portal inflammation, parenchymal inflammation, hepatocytic
      changes and duct proliferation), no statistical difference between groups
      submitted to extrahepatic biliary obstruction (EBO) with and without treatment
      with glutamine (G) was observed. CONCLUSION: Glutamine supplementation did not
      alter the prognosis of liver enzymes and histopathological changes in animals
      submitted to extrahepatic biliary obstruction.

PMID- 20676499
TI  - Electro-acupuncture reduces the need for additional anesthetics in experimental
      studies.
AB  - PURPOSE: To evaluate the possible beneficial effects of electro-acupuncture in
      rats subjected to ketamine/xylazine (KX) intra-peritoneal (i.p.) anesthesia.
      METHODS: Forty-eight male Wistar rats were distributed in four equal groups. All
      rats received i.p. injections of ketamine (90 mg/kg) +xylazine (10 mg/kg)
      anesthesia. Basal values group (control) rats (BV) received no additional
      treatment. The equivalent of the human right ST36 (Zusanli) and CV-12(Zhongwan)
      acupoints were chosen for needling and electrical stimulation. AC rats were
      needled with sterilized disposable stainless steel needles at right ST36 and CV12
      acupoints; needles were retained for 30 minutes. EAC10 rats, after needle
      insertion as described, had electrodes connected to both needles and to an
      electro stimulator model NKL EL-608; pulsed square waves, 10 Hz, 10 mA, was
      applied for 30 minutes. EAC100 rats were submitted to EA as described. However, a
      greater frequency (100 Hz) was used. RESULTS: Thirty-seven rats remained under
      adequate anesthetic level during the experiment. However, maintenance anesthesia
      was required by 11 rats. Need for additional anesthesia decreased to 9.1% in
      EAC100 rats compared to BV (36.3%). CONCLUSION: Both the AC and the EAC10/100
      prolong the anesthetic effect of the combination Ketamine-xylazine in rats,
      allowing longer duration of anesthesia with a lower dose of anesthetic, thereby
      reducing the occurrence of complications.

PMID- 20676501
TI  - Adult carbohydrate feeding affects reproduction of Phthorimaea operculella
      (Zeller) (Lepidoptera: Gelechiidae).
AB  - Reproduction of most insects depend on nutrients accumulated during the larval
      stage, but many lepidopteran species will also depend on nutrients obtained at
      the adult stage. Feeding at the adult stage allows the intake of carbohydrate and
      amino acid rich solutions, which may have an effect on the species reproduction
      and population growth. The objectives of the current study were to characterize
      the effects of sugar consumption by adults of the potato tuber moth, Phthorimaea
      operculella (Zeller), on its reproduction. To initially test the food intake by
      adults, a 10% honey solution or water (control), both containing a liquid dye
      were offered to adult insects 24 h after emergence, and the presence of the dye
      was observed by analysis of their digestive system. The effects of adult feeding
      on a 10% honey solution on the reproductive performance of P. operculella were
      evaluated by assessing the oviposition rate, fecundity and fertility. Adult
      feeding was proved by the presence of the dye within the digestive system of
      adults of P. operculella. Although the oviposition rate and fertility were not
      affected by adult feeding, female fecundity was higher in honey-fed females as
      compared to the water-fed females.

PMID- 20676502
TI  - [Biology of Tetranychus mexicanus (McGregor) (Acari: Tetranychidae) on three
      species of Annonaceae].
AB  - The mite Tetranychus mexicanus (McGregor) is considered a pest of a variety of
      plant species in the Americas. Although this mite apparently causes economic
      damage to Annonaceae, little is known about its biology. Here we studied the
      biology of T. mexicanus on soursop (Annona muricata), sweetsop (Annona squamosa)
      and araticum (Annona coriaceae). The first two species are the most important
      economical Annonaceae species in northeast Brazil; araticum is commonly found in
      the region, but not commercially explored. The mites were collected in the field
      from leaves of A. muricata and maintained in the laboratory for six months on
      detached leaves of A. muricata, A. squamosa and A. coriaceae, respectively,
      before observations started. Tetranychus mexicanus developed more slowly on A.
      squamosa than on the two other hosts, but oviposition was considerably lower on
      A. coriaceae. As indicated by the calculated life table parameters, biotic
      potential was higher on A. muricata than on the other hosts. Despite the observed
      differences in the T. mexicanus biology on the different evaluated hosts,
      development and reproduction were satisfactory in all of the hosts used.

PMID- 20676503
TI  - Reproductive behaviour of Crocidosema (=Epinotia) aporema (Walsingham)
      (Lepidoptera: Tortricidae): temporal pattern of female calling and mating.
AB  - Crocidosema aporema (Walsingham) is a major pest of legumes in the southern cone
      of Latin America. The mating behaviour of two allopatric populations (Uruguay and
      Brazil) of C. aporema kept in captivity was studied by observing the posture of
      calling females, the temporal pattern of pheromone emission and mating, and the
      response of males to calling females in olfactometer tests. Female calling and
      mating was observed during the scotophase, from the first to the seventh night
      after adult emergence. Male response was evaluated at night using a single
      calling female in a Y-shaped olfactometer. Females adopted a characteristic
      calling posture, extruding the pheromone gland from the tip of the abdomen. Most
      females started calling during the second scotophase, and all females called from
      the third, between the fifth and seventh hours after the onset of the scotophase.
      Most of the couples mated once throughout the experiment, between the third and
      sixth night and during the middle of the dark phase. Males preferentially chose
      the female arm in olfactometer tests, considering both the first arm chosen and
      the number of visits during the observation period. Our results describe for the
      fi rst time the temporal pattern associated to the reproductive behaviour of C.
      aporema. We also provide evidence that this tortricid is monoandrous, and that
      pheromones are used in intersexual communication for mate finding. Our data will
      be used to optimize the collection of female sex pheromones for chemical
      characterization in order to develop a monitoring tool for this pest.

PMID- 20676504
TI  - [Effect of endogenous factors on the chemical perception of Grapholita molesta
      (Busck) (Lepidoptera: Tortricidae) to sex pheromone].
AB  - The oriental fruit moth, Grapholita molesta (Busck), stands out as one of the
      most important pest in Rosaceae orchards in Brazil. During feeding, caterpillars
      bore into shoots, branches and fruits, impairing the commercial production. This
      work aimed to study the effect of endogenous factors in the chemical perception
      and in the species chemotactic behavior, seeking to optimize monitoring and the
      behavioral control of this pest. We evaluated male electroantennographical (EAG)
      and chemotactical (olfactometry) responses to the synthetic sex pheromone in
      different ages, virgins or mated and fed or unfed. The EAG responses of males did
      not differ for all evaluated factors. Nevertheless, the chemotactical behavior of
      males seems to decrease with age, not varying as a function of mating or feeding
      conditions. The knowledge about the interference of these factors in G. molesta
      may help with the interpretation of field results, allowing the development of
      suitable and reliable control measures based on infochemicals for behavioral
      control.

PMID- 20676505
TI  - [Compared biology and behavior of Tetranychus urticae Koch (Acari: Tetranychidae)
      and Phytoseiulus macropilis (Banks) (Acari: Phytoseiidae) on Bollgard and non
      transgenic isoline cotton].
AB  - The two spotted spider mite, Tetranychus urticae Koch, is a nontarget herbivore
      of Bt-cotton, but acquires and accumulates higher levels of Cry toxin than that
      expressed by transgenic plants. This work investigated the development and
      reproduction of T. urticae and of the predator Phytoseiulus macropilis Banks,
      during three successive generations looking for potential nontarget effect. In
      addition, behavioral studies on feeding preference, oviposition, and predation
      were carried out on Bt and non-Bt cottons. The development and reproduction of T.
      urticae and P. macropilis was conducted using leaf discs of Bt and non-Bt
      cottons. Arena containing leaf discs from both cotton types connected by a slide
      coverslip were also used in the behavioral studies. Averages of the three
      generations showed that the Bt-cotton does not affect the development, survival
      of immature stages, and reproductive output of T. urticae and of the predator P.
      macropilis. Furthermore, the preference for feeding and oviposition of T. urticae
      and P. macropilis were similar on both cotton types. In addition, P. macropilis
      exhibited similar predatory behavior on T. urticae fed on both cotton types.
      Levels of Cry1Ac toxin in T. urticae was 3.97 times greater than that found in
      the Bt-cotton plants as determined using a ELISA test. Despite of the amount of
      toxin acquired by the prey (T. urticae), no detectable levels of Cry1Ac were
      found in the predatory mite P. macropilis.

PMID- 20676506
TI  - Assembly rules in muscid fly assemblages in the grasslands biome of Southern
      Brazil.
AB  - The distribution of muscid species (Diptera) in grasslands fragments of southern
      Brazil was assessed using null models according to three assembly rules: (a)
      negatively-associated distributions; (b) guild proportionality; and (c) constant
      body-size ratios. We built presence/absence matrices and calculated the C-score
      index to test negatively-associated distributions and guild proportionality based
      on the following algorithms: total number of fixed lines (F L), total number of
      fi xed columns (F C), and the effect of the average size of the populations along
      lines (W) for 5000 randomizations. We used null models to generate random
      communities that were not structured by competition and evaluated the patterns
      generated using three models: general, trophic guilds, and taxonomic guilds. All
      three assembly rules were tested in each model. The null hypothesis was
      corroborated in all F L X F C co-occurrence analyses. In addition, 11 analyses of
      the models using the W algorithm showed the same pattern observed previously.
      Three analyses using the W algorithm indicated that species co-occurred more
      frequently than expected by chance. According to analyses of co-occurrence and
      guild proportionality, the coexistence of muscid species is not regulated by
      constant body size ratios. In fl ies of the grasslands, no rule was identified.
      Yet, a consensus did emerge from our analyses: species co-occur more frequently
      than expected by chance, indicating that aggregation is a recurring phenomenon
      among flies with saprophagous adults and predatory larvae. Therefore, competition
      does not seem to play an important role in the determination of muscid
      assemblages in the grasslands in Southern Brazil.

PMID- 20676507
TI  - [Diversity of Coccinellidae (Coleoptera) using aromatic plants (Apiaceae) as
      survival and reproduction sites in agroecological system].
AB  - Studies show that Apiaceae may provide concentrated vital resources for predator
      insects, stimulating their abundance, diversity and persistence in agricultural
      systems, thereby increasing their efficiency as biological control agents. Among
      the predatory insects, Coccinellidae (Coleoptera) on many different species both
      as larvae and adults, complementing their diet with pollen and/or nectar. This
      study aimed to determine the diversity and relative abundance of Coccinellidae
      species visiting plants of Anethum graveolens (dill), Coriandrum sativum
      (coriander) and Foeniculum vulgare (sweet fennel) (all Apiaceae), particularly in
      their blooming seasons, and to evaluate the potential of these aromatic species
      for providing the resources for survivorship and reproduction of coccinelids.
      Coccinellids were collected by removal of samplings from September to October,
      2007. Besides one unidentified species of Chilocorinae, five species of
      Coccinellinae were collected: Coleomegilla maculata DeGeer, Coleomegilla
      quadrifasciata (Schonherr), Cycloneda sanguinea (L.), Eriopis connexa (Germar)
      and Hippodamia convergens Guerin-Meneville. Dill provided a significant increase
      in the abundance of coccinellids as compared to coriander and sweet fennel. These
      aromatic species were used by coccinellids as survival and reproduction sites,
      providing food resources (pollen and/or prey), shelter for larvae, pupae and
      adults, and mating and oviposition sites as well.

PMID- 20676508
TI  - [Life cycle of Proprioseiopsis cannaensis (Muma) (Acari: Phytoseiidae) on
      different types of food].
AB  - Several annual and perennial crops are severely attacked by mites from the family
      Eriophyidae, Tenuipalpidae and Tetranychidae. A suitable alternative commonly
      used in several countries for the control of these pest mites involve the use of
      predatory mites in the family Phytoseiidae. The phytoseiid fauna in the Brazilian
      natural vegetation is very rich, but nothing is known about the biology of most
      of these species, as it is the case with Proprioseiopsis cannaensis (Muma). The
      objective of this study was to determine biological parameters of P. cannaensis
      fed on pest mite species such as Phyllocoptruta oleivora (Ashmead) (Eriophyidae),
      Brevipalpus phoenicis (Geijskes) (Tenuipalpidae) and Tetranychus urticae Koch
      (Tetranychidae). To enable a comparison for different food sources, one of the
      treatments consisted of pollen from Typha angustifolia L. The study was conducted
      in the laboratory at 25+/-1 masculineC, 80+/-10% RH and Photophase of 12 h.
      Proprioseiopsis cannaensis did not complete the development when it was fed on P.
      oleivora. Its fecundity was very low with all other food sources (maximum of 3.3
      eggs/female with pollen of T. angustifolia). The values of r m for P. cannaensis
      were -0.05, -0.09 and 0.002 when fed on B. phoenicis, T. urticae and pollen
      respectively. The unsatisfactory results from the four types of food sources do
      not permit us to conclude that P. cannaensis utilizes mites from the family
      Eriophyidae, Tenuipalpidae, Tetranychidae or pollen from different plant species
      as principal sources of food in nature.

PMID- 20676509
TI  - The importance of beta diversity in local gall-inducing arthropod distribution.
AB  - Many studies over the past twenty years have documented the richness of arthropod
      galling species around the world, and some have proposed hypotheses to explain
      local and global patterns of galling species richness. However, few studies have
      been directed toward understanding how the gall-inducing species are locally
      distributed. The aim of this study was to determine the distribution of gall
      inducing arthropods species at Coiba National Park, a tropical habitat on the
      Pacific coast of Panama. Our results suggest that more gall-inducing species had
      an aggregated distribution, and gall-inducing arthropod diversity shows a strong
      beta diversity component. Geographic distance was not correlated with similarity
      in gall-inducing species composition between the studied sites. This fact has
      important implications when trying to estimate gall-inducing arthropod richness
      and general patterns, and could cause contradictory results for hypotheses that
      attempt to explain the local and global patterns of galling species richness.

PMID- 20676510
TI  - Genetic variability of five Periplaneta americana L. (Dyctioptera: Blattidae)
      populations in southwestern Colombia using the AFLP molecular marker technique.
AB  - The genetic structure of five Periplaneta americana (L.) populations from three
      cities (Cali, Popayan and Buenaventura) located in southwestern Colombia was
      estimated using the AFLP molecular marker technique. A set of 174 loci were
      analyzed, 120 of which were polymorphic. Genetic diversity was estimated at
      different geographic levels for the total population and between cities. Genetic
      diversity averaged 0.32. The largest gene flow was detected between two
      population from Cali (F ST=0.088; Nm=2.6) and the lowest from the third
      population in this city (Univalle) and Popayan and Buenaventura (F ST=0.13;
      Nm=1.6 and F ST=0.12; Nm=1.8, respectively). The individuals' low mobility, the
      population' geographic separation, and possibly genetic drift have resulted in
      the population of this cockroach species having a significant degree of
      structuring, both between cities (Phist=0.13; P<0.001) and within them
      (Phist=0.87; P<0.001). These results suggest a high degree of subdivision within
      the P. americana population studied.

PMID- 20676511
TI  - Nesting behavior of Centris (Hemisiella) vittata Lepeletier (Hymenoptera: Apidae)
      in an area of the Cerrado in the northeast of the State of Maranhao, Brazil.
AB  - The nesting behavior of Centris (Hemisiella) vittata Lepeletier was studied in
      the Urbano Santos Cerrado in the northeast of Maranhao State, Brazil. To date,
      this species has only been studied in trap-nests. The nesting behavior of this
      species in a natural condition is recorded for the first time. Nesting occurred
      in preexisting holes in dead trunks of aroeira, Astronium myracrodruon
      (Anacardiaceae), at the end of the rainy season. The cells were constructed with
      a mixture of sand and oil. After finishing the nests, females used only oil to
      line the entrance wall. Two females collected sand at the same time to build
      their nests, and another one was seen collecting resources at Byrsonima sp.
      (Malpighiaceae). The pollen load of one bee was analyzed and was found to contain
      mainly Hymenaea courbaril (Leg-Caesalpiniaceae). Development from egg to adult
      took about 60 days. Protandry was observed, being males smaller than females. The
      nests were parasitized by Coleoptera and Diptera. However, the females only
      showed aggressive behavior against females of the same species or genus.

PMID- 20676512
TI  - [Morphology of the immature and adult stages of Neohydatothrips denigratus (De
      Santis) (Thysanoptera: Thripidae), with data on its biology].
AB  - The adult female of Neohydatothrips denigratus (De Santis) is redescribed, the
      male and immature stages (larva, prepupa and pupa) are described for the first
      time, and aspects of the biology of this species are made known. Descriptions of
      the different stages of development were made from laboratory-reared specimens on
      using twigs of Phaseolus vulgaris as a feeding and oviposition substrate.
      Neohydatothrips denigratus undergoes its life cycle on the leaves of P. vulgaris,
      no immature stages were found in flowers or fruits. Under controlled conditions
      (21+/-2 masculineC; 80+/-4% RH; photophase: 12 h), this species needed 21.6+/
      1.60 d to complete development (egg: 7.0+/-1.00 larva I: 3.7+/-1.40; larva II:
      4.2+/-1.10; prepupa: 1.8+/-0.70, pupa: 5+/-1). Longevity was 6.0+/-2.00 days and
      observed sex ratio was 2:1. From the sixteen plants belonging to ten families
      recorded as hosts to this species, larvae were found only on two species of
      Fabaceae and one of Solanaceae.

PMID- 20676513
TI  - [Coccus species affecting Coffea arabica in Brazil (Coccoideae: Coccidae) and the
      redescription of two species].
AB  - Five Coccus on Coffea arabica from the states of Bahia, Espirito Santo and Minas
      Gerais were studied. Females were prepared and mounted in Canada balsam. Coccus
      brasiliensis Fonseca and Coccus lizeri (Fonseca) were redescribed and Coccus
      alpinus De Lotto, Coccus celatus De Lotto and Coccus viridis (Green) were
      characterized. A key to species and illustration of all of them are included.
      Coccus alpinus and C. celatus are new records for Brazil and the Neotropical
      Region.

PMID- 20676514
TI  - [Biological aspects and external morphology of immature stages of Memphis moruus
      stheno (Prittwittz) (Lepidoptera: Nymphalidae)].
AB  - Immature stages of Memphis moruus stheno (Prittwittz) were subject of a behavior,
      biological and morphological study. The morphological study was carried out
      through observation by stereoscopic microscopy with camera lucida and micrometric
      lens attached for illustrations and measurements, respectively; and scanning
      electron microscopy for ultrastructural analysis. Behavioral data were obtained
      through direct observation in the field and laboratory. Eggs were laid on the
      underside of leaves of two Lauraceae species. The first to third instars build
      frass chains, the fourth and the fifth instars build a conical shelter using a
      single leaf of the host plant. Before pupation, larvae bend its body ventrally
      and the pupae are incapable of movement. Descriptions, illustrations and
      photographs of egg, all five instars and pupa are given. The cephalic morphology
      and chaetotaxy of first instar were described and illustrated. Results are
      compared with other Charaxinae immature stages.

PMID- 20676515
TI  - [Ovarian development and analysis of mating effects on ovary maturation of
      Diaphorina citri Kuwayama (Hemiptera: Psyllidae)].
AB  - As many other insects with a restricted diet, the citrus psyllid Diaphorina citri
      Kuwayama, which vector the causing agent of the Huanglongbing, the bacteria
      Candidatus Liberibacter spp., is intimately associated with symbiotic
      microorganisms. These mutualist symbionts play a key role on their host
      nutritional ecology, and are vertically transmitted to the progeny. However,
      despite the role symbionts play on host development and reproduction, and the
      growing opportunities of exploitation of the association insect-symbiont to
      control insect vectored-pathogens, there are very few studies on the host
      reproductive biology and on the symbiont transovarial transmission. Therefore, we
      aimed at analyzing the ovary development during D. citri adulthood, and at
      verifying for the mating requirement as a trigger to initiate ovary development.
      Newly-emerged D. citri females were grouped as virgin or mated and ovary
      development was observed during adulthood. Newly-emerged females have immature
      ovaries, and ovaries remain without any mature eggs until females mate. Once
      female mates, the vitellogenesis synthesis and uptake are estimulated, and
      oocytes are quickly developed. Oocytes maturation in ovarioles is metachronic,
      with only one oocyte developing at a time in each oogenic cycle. Morphological
      observations of the reproductive system including the ovaries and spermatheca,
      after the first cluster of eggs is laid, indicated D. citri is polyandrous, and
      may require multiple mating to develop additional oogenic maturation cycles.

PMID- 20676516
TI  - Use of serological techniques for determination of Spodoptera frugiperda(J E
      Smith) predators (Lepidoptera: Noctuidae).
AB  - Spodoptera frugiperda (J E Smith) is an important pest of several crops, but
      especially on maize in Brazil. The implementation of biological control measures
      hinges on the identification of its predators and other natural enemies. As a
      means of identifying predators, antibodies against S. frugiperda eggs were
      generated by inoculating rabbits with macerated S. frugiperda eggs, and the
      production of antibodies against S. frugiperda egg proteins was verifi ed by
      double immunodiffusion (DID). These antibodies were then utilized in another
      serological technique, counterimmunoeletrophoresis (CIE), to identify insects
      that could have ingested S. frugiperda eggs. Macerates of entire insects
      collected in maize plantations and of individual parts of their digestive tract,
      including the crop, were the source of antigens in the CIE, while predators fed
      S. frugiperda eggs in the laboratory served as the control. Antibodies produced
      by the inoculated rabbits were effective in detecting S. frugiperda egg proteins,
      especially if crop macerates were used as antigens. Among the species of insects
      collected from maize plantations, Lagria villosa Fabricius (Coleoptera:
      Lagriidae) and a species of Lygaeidae (Hemiptera) were identified as possible S.
      frugiperda predators.

PMID- 20676517
TI  - Distribution and abundance of natural parasitoid (Hymenoptera: Pteromalidae)
      populations of house flies and stable flies (Diptera: Muscidae) at the University
      of Florida Dairy Research Unit.
AB  - From September 2001 through September 2002, house fly and stable fly pupae were
      collected weekly from three fly habitats at the University of Florida Research
      dairy in northcentral Florida and evaluated for parasitism. Varying parasitism
      percentages were observed throughout the study but they were not affected by
      temperature, precipitation or fly abundance. Of the 6,222 house fly pupae and
      1,660 stable fly pupae that produced either a host fly or a parasitoid, 26.9% and
      26.7% were parasitized, respectively. Ten parasitoid species were recovered, with
      the genus Spalangia accounting for 85.7% of the total; the most common
      parasitoids attacking house fly and stable fly pupae were Spalangia endius Walker
      (33.9% and 27.3%), S. cameroni Perkins (27.9% and 40.6%), and S. nigroaenea
      Curtis (21.0% and 24.8%), respectively. Other parasitoids included one specimen
      of S. erythromera Forster and four specimens of Phygadeuon fumator Gravenhorst
      (Ichneumonidae). The percentage parasitism of pupae collected from bunker silos
      was higher than that of pupae from calf pens and open pastures. Spalangia
      cameroni was consistently recovered through the entire year. Spalangia nigroaenea
      was predominant in July, August, and September. Spalangia endius was most active
      from October to May with a peak of relative abundance in January.

PMID- 20676518
TI  - [Fitness of Bemisia tabaci (Gennadius) B Biotype (Hemiptera: Aleyrodidae)
      populations with different levels of susceptibility to the thiametoxam
      insecticide].
AB  - In two field-collected populations of de Bemisia tabaci (Gennadius) B biotype
      previously selected with the neonicotinoid insecticide thiamethoxam (NEO-R, NEO
      N), and a population susceptible to insecticides (SUSC), the level of response to
      the insecticide thiametoxam, as well as the life and fertility tables were
      determined. At LC95, the NEO-R population showed a resistance ratio (RR95) value
      of 8.8-fold, an intrinsic rate of increase (r m) of 0.72. The fitness of the NEO
      R and NEO-N populations in relation to the SUSC was 1.5 and 2.0, respectively.
      The RR95 value for NEO-N was 1.9-fold; it's r m value was 0.082, while in the
      SUSC population was 0.041. The developmental time of egg and adult were longer in
      NEO-R population, while the nymph and pupa lasted longer in the NEO-N and SUSC
      populations. The developmental time was different in the three NEO-R, NEO-N, and
      SUSC populations with 19.7 d (315.84 degree days or dd), 15.7 d (250.4 dd) and
      18.5 d (296.6 d), respectively. The populations previously selected with
      thiamethoxam did not reproduce faster than their susceptible counterpart.

PMID- 20676519
TI  - [Toxicity of spiromesifen to the developmental stages of Bactericera cockerelli
      (Sulc) (Hemiptera: Triozidae)].
AB  - Spiromesifen is an insecticide that inhibits the synthesis of lipids and, in
      Mexico, its use against the Tomato-Potato Psyllid, Bactericera cockerelli (Sulc),
      on chili pepper (Capsicum annum), tomato (Lycopersicon sculentum) and potato
      (Solanum tuberosum) began in 2005; however more information is needed to
      understand its toxicity on this insect pest. The aim of this research was to
      determine the toxicity of spiromesifen against each of the biological stages of
      tomato-potato psyllid, its effect on fertility and viability of eggs deposited by
      treated females, as well as the female preference to lay eggs on treated and non
      treated plants. The relative toxicity at 95% mortality (highest LC95 value /LC95
      value of the respective biological stage) of spiromesifen in egg, nymph 1, nymph
      2, nymph 3, nymph 4, and nymph 5 were 517.5; 31316.2; 2950.1; 315.6; 18.2 and 1
      fold, respectively. There were no differences in the toxicity of spiromesifen
      between adult males and females. The number of laid eggs was reduced as the
      spiromesifen concentration used to treat female increased and egg hatch was
      reduced in all tested doses. In the "no choice" test, females deposited 38.6+/
      2.01 eggs by leaf of non treated chili pepper type jalapeno, while in the treated
      with 360 mg L(-1) we observed 0.3+/-0.08 eggs by leaf. In the "choice" test, the
      oviposition decreased as the dose increased. There were no eggs on plants treated
      with 2400 mg L(-1) of spiromesifen.

PMID- 20676520
TI  - The population ecology of Muscina stabulans (Fallen) (Diptera: Muscidae), along
      an urban-rural gradient of Buenos Aires, Argentina.
AB  - The false stable fly, Muscina stabulans (Fallen), was surveyed along an urban
      rural gradient at Almirante Brown, Buenos Aires province, Argentina. Samples were
      taken at monthly intervals from May 2005 to April 2007. Hourly captures of adult
      flies (10:00 am-04:00 pm) were taken at each sampling date with a hand net. The
      baits used were 250 g of rotten cow liver and 250 g of fresh dog faeces exposed
      in shaded and sunny areas. The entire sample accumulated 358 specimens. The
      number of specimens captured during the second year was higher than in the fi rst
      year. Muscina stabulans was more abundant at urban-suburban sites. Females showed
      significant preferences for cow liver. We caught more specimens in shaded areas.
      The hourly activity increased toward the afternoon at the three sites. The
      present work was the first ecological study related to a muscid species in
      Argentina.

PMID- 20676521
TI  - [First record of Telenomus podisi (Ashmead) and Trissolcus urichi (Crawford)
      (Hymenoptera: Scelionidae) parasitizing eggs of the rice stem bug, Tibraca
      limbativentris (Stal) (Hemiptera: Pentatomidae), in Santa Catarina, Brazil].
AB  - We report the first occurrence of Telenomus podisi (Ashmead) and Trissolcus
      urichi (Crawford) parasitizing eggs of the Rice Stem Bug, Tibraca limbativentris
      (Stal), in Santa Catarina, Brazil. These species have a high potential of
      parasitization, pointing them as an alternative for biological control of T.
      limbativentris.

PMID- 20676522
TI  - Occurrence of Anopheles (Nyssorhynchus) rangeli (Gabaldon et al) and Anopheles
      (Nyssorhynchus) evansae (Brethes) (Diptera: Culicidae) in an eutrophized dam.
AB  - This is the first record of immature stages of species belonging to the subgenus
      Nyssorhynchus (Blanchard) in eutrophized breeding habitats. Larvae of Anopheles
      (Nys.) evansae (Brethes), Anopheles (Nyssorhynchus) rangeli (Gabaldon et al),
      Culex nigripalpus (Theobald) and Culex quinquefasciatus (Say) (Diptera:
      Culicidae) were collected in a rural eutrophized dam in Rio de Janeiro State, in
      Southeastern Brazil. Eutrophication was substantiated by the low diversity of
      mosquitoes, the high incidence of Cx. quinquefasciatus (42%) and of Daphinia sp.
      and, the high levels of both organic nitrogen (0.28 mg/l) and total phosphorus
      (0.02 mg/l).

PMID- 20676523
TI  - First record of Amblyomma scalpturatum Neumann (Acari: Ixodidae) in the states of
      Parana and Roraima, Brazil.
AB  - Amblyomma scalpturatum Neumann has been reported in Brazil in the northern
      (States of Amazonas, Para and Rondonia) and mid-western regions (States of Mato
      Grosso and Mato Grosso do Sul). It has been found in association with large and
      medium sized mammals, as Artiodactyla, Perissodactyla, Xenarthra and Carnivora.
      In this paper, this tick species is reported for the first time in the Brazilian
      states of Parana and Roraima, southern and northern regions, respectively.

PMID- 20676524
TI  - Green lacewings (Neuroptera: Chrysopidae) associated with melon crop in Mossoro,
      Rio Grande do Norte State, Brazil.
AB  - A survey of the green lacewings associated with the melon agroecosystem was
      carried out with the aim of including lacewings into the integrated management
      program of melon pests. Three species of this predator were found: Ceraeochrysa
      cubana (Hagen), Chrysoperla externa (Hagen) and Chrysoperla genanigra Freitas. A
      key to these species is presented.

PMID- 20676525
TI  - [Gallbladder polyps: how should they be treated and when?].

PMID- 20676527
TI  - [Who smokes does have more chance to show inguinal hernia?].

PMID- 20676528
TI  - [Platelet-Rich Plasma in knee injuries].

PMID- 20676529
TI  - [Smoking: Part 2].

PMID- 20676531
TI  - Phytophotodermatitis: an occupational and recreational skin disease.

PMID- 20676532
TI  - [Enzyme replacement therapy for mucopolysaccharidoses I, II and VI:
      recommendations from a group of Brazilian F experts].
AB  - Mucopolysaccharidoses (MPS) are rare genetic diseases caused by deficiency of
      specific lysosomal enzymes that affect catabolism of glycosaminoglycans (GAG).
      Accumulation of GAG in various organs and tissues in MPS patients results in a
      series of signs and symptoms, producing a multisystemic condition affecting bones
      and joints, the respiratory and cardiovascular systems and many other organs and
      tissues, including in some cases, cognitive performance. So far, eleven enzyme
      defects that cause seven different types of MPS have been identified. Before
      introduction of therapies to restore deficient enzyme activity, treatment of MPS
      focused primarily on prevention and care of complications, still a very important
      aspect in the management of these patients. In the 80's treatment of MPS with
      bone marrow transplantation/hematopoietic stem cells transplantation (BMT/HSCT)
      was proposed and in the 90's, enzyme replacement therapy (ERT),began to be
      developed and was approved for clinical use in MPS I, II and VI in the first
      decade of the 21st century. The authors of this paper are convinced that a better
      future for patients affected by mucopolysaccharidoses depends upon identifying,
      understanding and appropriately managing the multisystemic manifestations of
      these diseases. This includes the provision of support measures (which should be
      part of regular multidisciplinary care of these patients) and of specific
      therapies. Although inhibition of synthesis of GAG and the recovery of enzyme
      activity with small molecules also may play a role in the management of MPS, the
      breakthrough is the currently available intravenous ERT. ERT radically changed
      the setting for treatment of mucopolysaccharidosis I, II and VI in the last
      decade., Benefits can even be extended soon to MPS IV A (ERT for this condition
      is already in clinical development), with prediction for treatment of MPS III A
      and the cognitive deficit in MPS II by administration of the enzyme directly into
      the central nervous system (CNS). A large number of Brazilian services, from all
      regions of the country, already have experience with ERT for MPS I, II and VI.
      This experience was gained not only by treating patients but also with the
      participation of some groups in clinical trials involving ERT for these
      conditions. Summing up the three types of MPS, more than 250 patients have
      already been treated with ERT in Brazil. The experience of professionals coupled
      to the data available in international literature, allowed us to elaborate this
      document, produced with the goal of bringing together and harmonize the
      information available for the treatment of these severe and progressive diseases,
      which, fortunately, are now treatable, a situation which bring new perspectives
      for Brazilian patients, affected by these conditions.

PMID- 20676533
TI  - Molecular characterization of breast cancer in young Brazilian women.
AB  - OBJECTIVE: To evaluate the distribution of molecular subtypes of breast tumors
      diagnosed in young Brazilian women and to analyze the frequency of loss of
      heterozygocity (LOH) in BRCA1 among different molecular subtypes of early-onset
      breast cancer. METHODS: Samples from 72 cases of invasive breast carcinoma
      diagnosed in women aged between 19 and 40 years were evaluated using an
      immunohistochemical panel of biomarkers. Three intragenic BRCA1 locus
      microsatellites, D17S1322, D17S1323, and D17S855, were PCR amplified from matched
      normal (lymphocyte) and tumor DNAs for (LOH) analysis. RESULTS: We found 13 cases
      (18%) that had an immunohistochemical profile consistent with being basal-like.
      Forty cases (55%) were luminal A type; 11% (8 cases) were luminal B type, 13% (9
      cases) were HER2-overexpressing tumors and two cases were ER-/HER2- carcinomas
      lacking basal marker expression. Four of the 16 informative cases at D17S1322,
      one of the four informative cases at D17S855, and none of the five informative
      cases at D17S1323 displayed LOH (four basal-like and one Luminal A).
      Microsatellite instability (MSI) at D17S855 and D17S1322 was found in two cases
      (one a basal-like and one Luminal A). CONCLUSION: In our study, basal-like tumor
      was the second most frequent molecular type among young Brazilian women and was
      only observed in women diagnosed under the age of 35 years. There was no
      significant difference of LOH at BRCA1 locus rates between basal-like breast
      tumors and not-basal-like breast tumors (p=0.62). LOH in BRCA1 and MSI in these
      breast cancers were not frequent but may indicate a small group of breast cancers
      with a specific molecular makeup.

PMID- 20676534
TI  - [Cerebral venous thrombosis: study of fifteen cases and review of literature].
AB  - OBJECTIVE: To analyze a series of 15 patients with cerebral venous thrombosis
      (CVT) who had follow-ups at the neurology service of Santa Casa de Belo Horizonte
      Hospital from April, 2007 to December, 2008. These results were compared with
      data in literature. METHODS: Cases were evaluated by retrospective study of the
      epidemiologic characteristics, signs and symptoms, risk factors and prognosis of
      15 patients with cerebral venous thrombosis. RESULTS: Diagnoses were reached
      through magnetic resonance imaging of the brain in 14 cases and through an
      angiography in one. The main risk factors identified were use of birth control
      pills (40%) and history of family member with deep venous thrombosis.
      Thrombophilia was found in two patients (13%). The veins more affected were the
      transverse sinus (73%) followed by the upper sagital sinus (53%). Four patients
      had strokes and five had only headaches as isolated symptoms. Twelve patients
      were treated with heparin and oral anticoagulant. CONCLUSION: Treatment with
      heparin in the acute phase followed by an oral anticoagulant was shown as safe
      and efficient to prevent worsening of the disease, recurrence and for quick
      improvement of neurological symptoms of all treated patients. CVT is one of the
      possible diagnoses of secondary headache even in patients with no signs and
      symptoms.

PMID- 20676535
TI  - Cardiovascular risk factors and metabolic syndrome in a population of young
      students from the National University of Colombia.
AB  - OBJECTIVE: To estimate prevalence and distribution of cardiovascular risk factors
      and Metabolic Syndrome (MS) in young individuals admitted to the National
      University of Colombia in Bogota. METHODS: An analytic cross-sectional study was
      conducted in a sample of 249 individuals of both genders aged 15 to 20 years. A
      questionnaire was personally administered to collect demographic, socioeconomic,
      smoking, perinatal, and women's health data. Anthropometric measurements, blood
      pressure, and a fasting blood sample were taken. Prevalence of MS was determined
      and compared using criteria from several qualified institutions. RESULTS: We
      found a high prevalence of smoking (18.9%), arterial prehypertension (14.1%) and
      overweight (11.2%), 9.2% of study participants had prediabetes, and the most
      frequent dyslipidemia was low HDL cholesterol (13.3%). Alcoholic beverage
      consumption was declared by 60.6% of study terol and plasma triglyceride levels.
      Gestational age at birth was inversely associated with presence of low HDL
      cholesterol levels and high blood pressure. Prevalence of the MS varied markedly
      according to the definition employed: 9.2% using REGODCI (Research Group on
      Diabetes and Chronic Illnesses) criteria, 2% using IDF (International Diabetes
      Federation) criteria, and 2.4% using AHA (American Heart Association) criteria.
      CONCLUSION: The encountered prevalence of modifiable cardiovascular risk factors
      justifies promotion of therapeutic lifestyle changes among this age group in
      Colombia. Further harmonization of MS criteria in young individuals is needed.

PMID- 20676536
TI  - [GSTM1 and GSTT1 genes analysis in head and neck cancer patients].
AB  - OBJECTIVE: To establish the clinical and demographic profile and identify risk
      factors among patients with head and neck cancer and relate them to the
      polymorphism of GSTT1 and GSTM1. METHODS: One hundred patients with head and neck
      cancer and 100 control group individuals without history of neoplasm were
      analyzed. . The molecular analysis were made by multiplex polymerase chain
      reaction. For statistical analysis, data were tabulated and compared by the
      Fisher's exact test, the Chi-square test and multiple logistic regression were
      also used. RESULTS: There was prevalence of smokers (OR = 5.32, CI 95% CI = 2.04
      13.86 p = 0.0006), alcohol drinkers (OR = 5.04, CI 95% = 2.19-11.59 p = 0.0001)
      in head and neck cancer patients . The GSTT1 null genotype was found in 47% of
      the patient and 41% of the control group (OR = 0.67; CI 95%= 0.34-1.35; p =
      0.2648). Likewise , the GSTM1 null genotype was found in 66% of the patient and
      75% of the control group (OR = 2.25; CI 95%= 1.05 - 4.84; p = 0.0368). The
      combined GSTT1 and GSTM1 gene null genotype shown association between GSTM1
      0/GSTT1 and occurrence of head and neck carcinoma (OR = 7.64; CI 95%= 1.72-34.04;
      p = 0.0076). Analysis of clinical-pathological features showed association
      between GSTT1 null genotype and larynx, the inverse relation between this
      genotype and pharynx. CONCLUSION: In our study it was possible to establish
      association between GSTM1 null genotypes and head and neck cancer.

PMID- 20676537
TI  - [Secular trends in stature growth in Blumenau-Brazil in relation to human
      development index (HDI)].
AB  - OBJECTIVE: The objective of this study was to analyze the secular trend of growth
      in height of military recruits enlisted in Blumenau and correlate it with the HDI
      index. METHODS: This was a cross-sectional study of recruits aged 18 to 20
      enlisted to the 23rd Infantry Battalion in Blumenau between 1963 to 2007. The
      sample comprised 600 out of a total of 3000 recruits enlisted over the period.
      Data were collected from individual enlistment files on recruits which had been
      archived by year. Three years were analyzed from each decade (x3, x5, and x7) and
      the first forty files were selected systematically from each recruitment year for
      analysis. Statistical analysis was with descriptive statistics, Student's t test
      and simple linear regression. RESULTS: There was an increase of the order of 7 cm
      in the height of recruits in Blumenau over the last 47 years (from 1.7 meters in
      the 1960s to 1.77 meters in the 2000s) and the increase was most evident between
      the 1970s and 1980s. The mean heights in years in different decades exhibited a
      strong and positive correlation with the HDI in Blumenau and Brazil, which both
      increased progressively during the study period. CONCLUSION: The secular tendency
      in growth in height was positive in Blumenau and had a positive correlation with
      HDI.

PMID- 20676538
TI  - [Cancer mortality trends in Brazilian state capitals, 1980-2004].
AB  - OBJECTIVE: Cancer mortality rates began to decline in developed countries in the
      1990s, but their behavior in developing countries is less well-known. An earlier
      study on cancer mortality in Brazil showed a declining mortality trend for cancer
      as a whole. however the quality of data results raised some criticism t. The
      population of state capitals comprises about a quarter of the total Brazilian
      population and for these cities mortality data available have a better quality
      than for the entire country, enabling analyses of trends in cancer rates based on
      more accurate data. METHODS: Mortality and population data were collected from
      government databases (SIM/DATASUS and IBGE, respectively). Age-adjusted (world
      standard) and age-specific mortality rates were calculated for both genders .
      Linear regression was used to investigate changes in trends. RESULTS: For all
      cancers as a whole mortality rates declined throughout the study period for both
      men and women (-4.6% and -10.5%, respectively). For both genders , the cancer
      that decreased most was stomach cancer. Among men, lung cancer death rates
      presented a slight reduction, while prostate cancer rates increased. Among women,
      "uterus, site unspecified' presented a downward trend, while lung cancer rates
      increased. The trend for breast cancer remained stable, and cervix uterus rates
      showed a slight increase at the end of the period. CONCLUSION: As already seen in
      developed countries, all cancer mortality rates tended to decline in Brazilian
      state capitals over the period 1980-2004, a tendency largely due to a decline in
      stomach cancer death rates for both genders.

PMID- 20676539
TI  - Experience with the ABC Foundation School of Medicine undergraduate meeting.
AB  - OBJECTIVE: To quantify the number of studies that were presented during oral
      sessions, selected for awards and published from 2002 to 2007 at the
      Undergraduate Medical Congress of ABC at the ABC Foundation School of Medicine.
      METHODS: A retrospective systematic survey of papers selected for oral
      presentation and award at these undergraduate meeting from 2002 to 2007 was
      carried out by searching Medline and Lilacs databases and the annals of other
      medical meetings in order to ascertain which papers would eventually be
      published. RESULTS: From 2002 to 2007, 408 papers were selected for oral
      presentation and 71 (17.4%) received at least one award. The total number of
      papers published was 138 (33.8%), of which 33 (8.1%) were in Medline, 57 (14%) in
      Lilacs and 48 (11.7%) in the annals of other scientific meetings. Receiving an
      award by the scientific committee was an independent variable for publication
      (OR: 2.05 95% CI 1.22-3.46, p = 0.006) as well as for publication in Medline (OR:
      2.62 95% CI 1.21 - 5.69, p = 0.01). CONCLUSION: The institutional scientific
      production of undergraduate medical students presented in Undergraduate Medical
      Meetings is relevant and should continue to be stimulated.

PMID- 20676540
TI  - [Gallbladder polyps: how should they be treated and when?].
AB  - OBJECTIVE: The objective of this study was to determine the correct therapeutic
      management for patients with gallbladder polyps (GPs), what type of surveillance
      should be employed and how to differentiate between benign and malignant polyps
      in addition to also to providing reassurance in cases of "cancerophobia". STUDY
      DESIGN: This was a 5-years retrospective study. LOCATION: The study was conducted
      at a Surgery Department at the Hospitais da Universidade de Coimbra. POPULATION:
      We analyzed all patients operated on at the Surgery Service II from January 2003
      to December 2007 who had had a preoperative diagnosis of GP. METHODS:
      Clinicopathological correlations were traced for all patients. The following were
      analyzed: demographic data, clinical presentation, principal symptoms, associated
      pathologies, supplementary tests and diagnoses. RESULTS: We studied 93 patients,
      91 of whom had benign polyps and two of whom had malignant polyps. Of the 91
      benign polyps, 73 (78.5%) were cholesterol polyps, 14 (15%) were hyperplastic and
      two (2.2%) were adenomas. Two (2.2%) patients had malignant polyps, both
      adenogallbladder carcinomas. The mean diameter of benign polyps was 6 mm and 40
      (43%) patients had multiple lesions. The mean diameter of malignant and
      premalignant polyps taken together was 18.8 mm, all were single polyps and the
      mean age of this patient subset was 57.7 years. CONCLUSION: It was concluded that
      the surgical option for GPs is cholecystectomy and that this should only be
      undertaken in cases where there are clinical signs of GP; polyps with diameters
      greater than 10 mm; fast-growing polyps; sessile polyps or wide-based polyps;
      polyps with long pedicles; patient aged over 50; concurrent gallstones; polyps of
      the gallbladder infundibulum or abnormal gallbladder wall ultrasound.

PMID- 20676541
TI  - [The cost of liver transplantation at a university hospital of Brazil].
AB  - OBJECTIVE: To investigate if liver transplants were cost effective at a
      University Hospital of Ceara. METHODS: We evaluated data from the medical records
      of 62 liver transplant patients performed in 2007, from the day of admission for
      the transplant to the date of discharge or death. Indicators such as length of
      hospital stay and location ,quantity of medical material and medication used, as
      well as the investigations and procedures performed were determined. RESULTS: The
      population was mostly male from the Northeast of Brazil with an mean age of 45
      years. The mean total cost of a liver transplant was US$20,605.01. The largest
      part was payment for the professional team involved in the liver removal and
      transplant, followed by hospital stay , medication used during surgery and
      hospitalization, and products (medication and materials) used in the liver
      removal. According to the current schedule, the SUS made the following payments
      to HUWC; US$1,322.97 for liver removal, US$3,223.56 for medical fees and
      US$32,235.68 for the package including the complete surgical procedure, hospital
      expenses and care up to the seventh day of hospitalization. CONCLUSION: Results
      were similar to those found by other Brazilian transplant centers. Liver
      transplantation in Ceara is an economically viable procedure based upon the
      financial transfer from SUS.

PMID- 20676542
TI  - [Factors related to falls of elderly women residents in a community].
AB  - OBJECTIVE: To determine the factors related to falls of a group of independent
      and autonomous elderly women. METHODS: This was a descriptive study of 83 elderly
      women enrolled on the Elderly Health Promotion Project at the Universidade
      Catolica de Brasilia. They replied to questionnaires on their age,
      sociodemographic factors, dizziness, use of continuous medication, self
      perception of health and vision and underwent the Yesavage Geriatric Depression
      Scale, Functional Reach Test and Tinetti Performance-Oriented Mobility
      Assessment. RESULTS: No statistical relationship was identified between age,
      social demographic factors, dizziness, or negative self-perception of health and
      vision and fall phenomena. However there was a significant statistical
      relationship with the Functional Reach Test and Tinetti Performance-Oriented
      Mobility Assessment. CONCLUSION: Elderly women's ability to balance was the major
      factor related to fall events. Functional Reach Test and Tinetti Performance
      Oriented Mobility Assessment were considered effective for predicting risk of
      falling, indicating that they could be used for assessment and identification of
      improved balance after training

PMID- 20676543
TI  - [Prevalence and factors associated with practice of episiotomy at a maternity
      school in Recife, Pernambuco, Brazil].
AB  - OBJECTIVE: To determine the prevalence and factors associated with episiotomy in
      a reference center of Pernambuco. METHODS: A retrospective cross-sectional study
      was carried out from January to December 2006 with 495 women who had a normal
      delivery at the Maternity Center Monteiro de Moraes Integrated Health Amaury de
      Medeiros (CISAM) University of Pernambuco. Assessed factors were issues
      preceeding birth, characteristics of labor and perinatal outcome. To verify the
      association between predictors and performance of episiotomy the Chi square,
      Fisher's exact and Student's t tests were used as appropriate, with a a
      significance level of 5%. The prevalence ratio and confidence intervals were
      calculated at 95%, in addition to logistic regression analysis. RESULTS:
      Prevalence of performing episiotomy was 29.1% (n = 144). After bivariate
      analysis, we found a significant association of episiotomy with adolescence (PR
      1.74. 95% CI 1.33-2.28), age over 35 years (PR 0.35. 95% CI 0.14-0.90),
      primiparity (PR 4.73, 95% CI 3.33-6.71), absence of previous vaginal delivery (PR
      5.44, 95% CI 3.67-8.06) and related diseases at the time of delivery (RP 1.71,
      95% CI 1.30-2.25). There was no significant relation with gestational age at
      delivery, duration of labor over 6h and expulsion period of more than 30 minutes,
      use of misoprostol or oxytocin, abnormal fetal heart rate, presence of meconium,
      shift of completion of delivery (night or day), rate of Apgar score in 1 and 5
      minutes and weight of the newborn. Presence of perineal lacerations was higher in
      the group not subject to episiotomy, however only 1st and 2nd degree lacerations
      were described. After logistic regression, the analyzed remaining factors
      associated with episiotomies were maternal diseases (RA 1.99, 95% CI 1.20-3.28)
      and absence of previous vaginal delivery (9.85 RA, 95% CI 6.04-16.06).
      CONCLUSION: Prevalence of episiotomies in the institution was 29%. Variables that
      remained related to episiotomy were maternal diseases and absence of previous
      vaginal delivery.

PMID- 20676544
TI  - [Human T cell lymphotropic virus (HTLV-1): when to suspect infection?].
AB  - Human T-cell lymphotropic virus (HTLV) infections have occurred for thousands of
      years. However, knowledge about their pathogenesis is recent. The virus is
      endemic in several regions around the world. In Brazil, it is present in all
      states at varying prevalence rates and it has been estimated that around 2.5
      million Brazilians are infected. Genetic and immunological parameters of the host
      are the most important determinants of the clinical manifestations associated
      with infection. These can be divided into three categories: neoplastic,
      inflammatory and infectious. HTLV-associated myelopathy (HAM/TSP) and adult T
      cell leukemia/lymphoma (ATLL) were the first diseases to be related to this
      retrovirus. More recently, countless other diseases have been correlated with the
      virus. The objective of this review is to provide an update on epidemiological,
      pathophysiologic, therapeutic and, primarily, diagnostic knowledge about HTLV, in
      order to encourage etiologic suspicion of HTLV in all its diverse clinical
      manifestations, which are currently rarely associated with this agent.

PMID- 20676545
TI  - [Retropubic and transobturator sling in treatment of stress urinary
      incontinence].
AB  - OBJECTIVE: To compare the results of retropubic and transobturator slings for
      surgical treatment of female stress urinary incontinence (SUI). METHODS: We
      randomized thirty patients with SUI, ten of whom underwent transobturator sling
      surgery and ten retropubic sling surgery. Patients were assessed before treatment
      and 1, 6 and 12 months after treatment on the basis of clinical history, physical
      examination, quality of life questionnaire (King's Health Questionnaire), pad
      test and urodynamic evaluation. The groups were homogenous prior to surgery.
      RESULTS: One year after surgery, incontinence and quality of life parameters had
      improved significantly in both groups and there were no differences between them.
      There was a significant reduction in pad test weights in both groups. According
      to the urodynamic evaluation, 12 months after surgery cure rates were 84.2% for
      the transobturator group and 88.8% for the retropubic group. Subjective cure
      rates were 85% in the transobturator group and 88.8% in the retropubic group. No
      statistical difference was observed in complication rates. CONCLUSION: Retropubic
      and transobturator slings were effective for treatment of women with SUI at 12
      month follow-up. Both techniques had significant cure rates and improved quality
      of life with low complication rates.

PMID- 20676546
TI  - [Vitamin A and gestational diabetes].
AB  - Diabetes mellitus (DM) a pathology with chronic evolution, has now acquired a
      connotation of global epidemic. Gestational diabetes, a condition associated with
      insulin resistance and decreased beta-cells function is also characterized by a
      high incidence in different populations and ethnic groups. Recently strong
      evidence has been found for involvement of retinol levels of pregnant women with
      DM due to the pathology's evolution. This condition makes these diabetics prone
      to have a marginal biochemical profile or a vitamin A deficiency when compared to
      those of healthy pregnant women. Therefore, with an awareness of the
      physiological role of vitamin A and consequences of diabetes during pregnancy,
      this review intends to clarify the impact of DM on retinol levels of these
      pregnant women and the consequences that vitamin A deficiency may cause to these
      women and their infants.

PMID- 20676547
TI  - [General principles for treatment of early rheumatoid arthritis].
AB  - The main goals of the treatment of a patient with RA are: to reduce pain, joint
      swelling and constitutional symptoms such as fatigue, to improve joint function,
      stop progression of bone-cartilage damage , prevent disabilities and reduce
      morbidity and mortality. In recent years, the therapeutic concept of early RA
      (first 12 months of symptoms) has undergone major changes. Three aspects in
      particular have become the basis of the new treatment paradigm: early diagnosis,
      immediate beginning of Disease Modifying Antirheumatic Drugs therapy (DMARD) and
      strict control of the inflammatory activity. In this article, the authors review
      the general principles of management of patients with early RA.

PMID- 20676548
TI  - [Brazilian lyme-like disease or Baggio-Yoshinari syndrome: exotic and emerging
      Brazilian tick-borne zoonosis].
AB  - Lyme disease (LD) is a frequent zoonosis found in the Northern Hemisphere and is
      considered an infectious disease caused by spirochetes belonging sensu lato to
      the Borrelia burgdorferi complex transmitted by ticks of the Ixodes ricinus
      group. In 1992, first cases similar to LD were described in Brazil, when
      brothers, after a tick bite episode developed symptoms , as erythema migrans,
      general flu-like symptoms and arthritis. Careful analysis of Brazilian LD-like
      illness casuistry showed that epidemiological, clinical and laboratorial features
      in the country were very different from those exhibited by North American and
      Eurasian LD patients. Human blood-suckers Ixodes ricinus complex ticks were
      absent at risk areas; the disease is recurrent in the country; Borrelia
      burgdorferi was never isolated in Brazil and specific serologic tests have shown
      little positivity with inconsistent results. Furthermore, peripheral blood
      analysis of patients on electron microscopy exhibited structures resembling
      Mycoplasma spp, Chlamydia spp and spirochete-like microorganisms. In fact, they
      were assumed to be latent forms of spirochetes (L form or cell wall deficient
      bacteria) adapted to survive at inhospitable conditions in vertebrate and
      invertebrate hosts. For these reasons, the Brazilian zoonosis was named Baggio
      Yoshinari Syndrome (BYS) and defined as: "Exotic and emerging Brazilian
      infectious disease, transmitted by ticks not belonging to the Ixodes ricinus
      complex, caused by latent spirochetes with atypical morphology, which originates
      LD-like symptoms, except for occurrence of relapsing episodes and auto-immune
      disorders".

PMID- 20676549
TI  - [New findings about vaginal bacterial flora].
AB  - The aim of this review is to update knowledge about the vaginal ecosystem, non
      cultivation methods for bacterial identification (gene amplification), the
      Lactobacillus species that comprise normal vaginal flora and influence of host
      genetics on bacterial interactions with local innate and acquired immune
      defenses. A Medline (Pubmed) search from 1997-2009 for relevant articles was
      performed and the most informative articles were selected. Non-culture techniques
      (gene amplification) allow a comprehensive analysis of the vaginal ecosystem's
      composition. In the majority of women in the reproductive age there is a
      predominance of one or more species of Lactobacillus: L. crispatus, L. inners and
      L gasseri. However, in other apparently healthy women there is a deficiency or
      complete absence of Lactobacilli. Instead, there is a substitution by other
      lactic acid-producing bacteria: Atobium, Megasphaera and/or Leptotrichia species.
      The infectivity and/or proliferation of pathogenic bacteria in the vagina is
      suppressed by lactic acid production, by products of endogenous bacteria and by
      activation of local innate and acquired immunity. Vaginal epithelial cells
      produce several compounds with anti-microbial activity. These cells have Toll
      like receptors on their membrane that recognize molecular patterns associated
      with pathogens. Recognition leads to production of pro-inflammatory cytokines and
      stimulation of antigen-specific immunity. The production of IgG and IgA
      antibodies is also triggered in the endocervix and vagina in response to
      infection. Vaginal flora composition and the immune mechanisms constitute
      important defenses. Criteria of normal and abnormal flora have to be reviewed and
      genetic polymorphism can explain variations in flora composition. This new
      knowledge should be included in the clinical practice of gynecologists and
      obstetricians to improve patients care.

PMID- 20676550
TI  - Assessment of teaching-health care integration and performance in university
      hospitals.
AB  - OBJECTIVE: To assess the performance and integration between the health care and
      teaching dimensions in Brazilian university hospitals. METHODS: A network data
      envelopment analysis (DEA) model was designed to measure the performance of
      federal university hospitals, which enables the relationship between the teaching
      and health care dimensions to be considered simultaneously. Data from the
      Ministry of Education Information System of University Hospitals, in the second
      semester of 2003, were used. Results of the network model were compared to those
      of classical DEA models to assess the advantages of the new methodological
      proposal. RESULTS: The efficiency of the hospitals assessed varied between 0.19
      and 1.00 (mean = 0.54). The dimensional score showed that hospitals prioritize
      the gain in health care efficiency. It was observed that there was a need to
      double the number of medical students and increase the number of residents by 14%
      to obtain efficiency in the teaching dimension. CONCLUSIONS: The model was useful
      for both unit managers, aiming to integrate teaching and health care, and
      regulatory organizations, when defining policies and incentives.

PMID- 20676551
TI  - Medicine use from birth to age two years: the 2004 Pelotas (Brazil) Birth Cohort
      study.
AB  - OBJECTIVE: To describe medicine use by children at three, 12 and 24 months of
      age. METHODS: Cross-sectional study using data from the 2004 Pelotas Birth Cohort
      (Southern Brazil), including: 3,985 children at three months, 3,907 children at
      12 months, and 3,868 children at 24 months of age. The outcome investigated was
      use of medicine in the 15 days preceding the interview. Information on
      independent variables (medicine used, who indicated it, how it was obtained,
      periodicity of use, and therapeutic group) were collected using a standardized
      questionnaire administered during a home interview with the child's parents.
      RESULTS: Prevalence of medicine use at three, 12, and 24 months was 65.0% (95%
      CI: 63.5;66.5), 64.4% (95% CI: 62.9;65.9), and 54.7% (95% CI: 53.1;56.2),
      respectively. As age increased, there was a reduction in the total number of
      medicines used and an increase in self-medicine, which reached 34% at 24 months.
      Furthermore, frequency of sporadic medicine use increased, while that of
      continuous use decreased. Medicine was purchased mainly using private resources,
      with roughly 10% of drugs being purchased through the Brazilian National Health
      Care System. The profile of medicine types used also changed with age. The type
      of medicine most frequently used were dermatological products (36%) at three
      months; respiratory system drugs (24%) at 12 months; and analgesics (26%) at 24
      months of age. Compared to three months, medicine use at 24 months was
      characterized by decreased use of digestive tract and metabolism drugs, drugs for
      the sensory organs, cardiovascular system drugs, and dermatological products, and
      an increase in systemic anti-infectious drugs, medicine for the skeletomuscular
      and respiratory systems, analgesics, insecticides, and repellents. CONCLUSIONS:
      Medicine use in this cohort was high and indicates the need for prioritizing
      rational use of medicine in early life.

PMID- 20676552
TI  - Use of medicines by persons with disabilities in Sao Paulo state areas,
      Southeastern Brazil.
AB  - OBJECTIVE: To analyze the use of medicines and the main therapeutic groups
      consumed by persons with physical, hearing and visual disabilities. METHODS: A
      cross-sectional study was performed, where data from the 2002 Inquerito
      Multicentrico de Saude no Estado de Sao Paulo (ISA-SP - Sao Paulo State
      Multicenter Health Survey), as well as the 2003 Inquerito de Saude no Municipio
      de Sao Paulo (ISA-Capital - City of Sao Paulo Health Survey), Southeastern
      Brazil, were analyzed. Respondents who reported having disabilities were studied,
      according to variables that comprise the database: geographic area, gender,
      income, age group, ethnic group, use of medicines and types of drugs consumed.
      RESULTS: The percentage of use of drugs by persons with disabilities was 62.8%
      among the visually impaired; 60.2% among the hearing impaired; and 70.1% among
      the persons with physical disabilities. Individuals with physical disabilities
      consumed 20% more medications than non-disabled ones. Among persons with visual
      disabilities, the most frequently consumed drugs were diuretics, agents of the
      renin-angiotensin system and analgesics. Persons with hearing disabilities used
      more analgesics and agents of the renin-angiotensin system. Among those with
      physical disabilities, analgesics, antithrombotics and agents of the renin
      angiotensin system were the most frequently consumed medicines. CONCLUSIONS:
      There was a greater use of medicines among persons with disabilities than non
      disabled ones. Persons with physical disabilities were those who most consumed
      medicines, followed by the visually impaired and the hearing impaired.

PMID- 20676553
TI  - Rational use of anticancer drugs and patient lawsuits in the state of Sao Paulo,
      Southeastern Brazil.
AB  - OBJECTIVE: To assess the rationality of legal suits and administrative requests
      requiring anticancer drugs filed against and submitted to the Sao Paulo State
      Department of Health, in view of scientific evidence on efficacy and safety.
      METHODS: A descriptive cross-sectional study was carried out based on information
      on lawsuits filed by cancer patients requiring anticancer drugs were furnished by
      the Department of Health. These drugs are among those having the greatest
      financial impact on the Brazilian Health System in 2006 and 2007. The drugs were
      assessed according to clinical evidence on efficacy and safety, based on
      Micromedex categorization, on systematic reviews and meta-analyses. Indications
      present in the legal documentation were compared to the indications approved by
      regulatory agencies. RESULTS: Bevacizumab, capecitabine, cetuximab, erlotinib,
      rituximab, imatinib, and temozolomide accounted for expenses over R$ 40 million
      to meet 1220 requests and lawsuits, at an average cost of R$ 33,500 per patient.
      Selected studies do not recommend all the indications for the prescribed drugs.
      Approximately 17% of requests and lawsuits did not provide evidence for the
      required indication, and these amounted to inappropriate expenses of, at least,
      R$ 6.8 million. CONCLUSIONS: The results reinforce the need for technical
      expertise in dealing with legal suits and for capacity-building of health
      professionals in approaching the scientific literature, in order to appropriately
      select drugs and to ensure the best therapeutic decision for each clinical
      condition, and thus guarantee access to safe and effective health technologies
      and, therefore, to enhance the quality of the Brazilian pharmaceutical services
      model in oncology.

PMID- 20676554
TI  - Correction for reported cervical cancer mortality data in Brazil, 1996-2005.
AB  - OBJECTIVE: To develop a methodology for correction of reported cervical cancer
      deaths in Brazil. METHODS: Data on 9,607,177 cancer deaths were obtained from the
      Brazilian National Mortality Database for the period between 1996 and 2005. For
      correction of underreporting of deaths, factors generated by the Global Burden of
      Disease Study in Brazil-1998 were used. Proportional distribution was used in
      order to correct the categories of unknown, incomplete or ill-defined death
      diagnosis. The corrections were applied to each Brazilian state and the results
      were presented for Brazil nationwide, macroregions, and geographical areas
      (capital, other cities of metropolitan areas and interior cities) as percent
      variability of cervical mortality rates before and after correction. Corrections
      were analyzed by multivariate linear regression with interaction terms between
      macroregion and geographical area. RESULTS: After correction, cervical cancer
      mortality rates showed an increment of 103% nationwide, ranging between 35%
      (Southern region capitals) and 339% (Northeastern region interior cities). The
      reallocation of cervical cancer deaths not otherwise specified resulted in
      greater mortality rate increments. The percent correction by year of death
      revealed steady trends nationwide. CONCLUSIONS: The study results showed that the
      proposed methodology was appropriate for the correction of cervical cancer
      mortality rates in Brazil. It evidenced that cervical cancer mortality is even
      higher than that reported.

PMID- 20676555
TI  - Epidemiological profile of patients on renal replacement therapy in Brazil, 2000
      2004.
AB  - OBJECTIVE: To describe the clinical and epidemiological profile of patients under
      renal replacement therapies, identifying risk factors for death. METHODS: This is
      a non-concurrent cohort study of data for 90,356 patients in the National Renal
      Replacement Therapies Database. A deterministic-probabilistic linkage was
      performed using the Authorization System for High Complexity/Cost Procedures and
      the Mortality Information System databases. All patients who started dialysis
      between 1/1/2000 and 12/31/2004 were included and followed until death or the end
      of 2004. Age, sex, region of residence, primary renal disease and causes of death
      were analyzed. A proportional hazards model was used to identify factors
      associated with risk of death. RESULTS: The prevalence of patients under renal
      replacement therapies increased an average of 5.5%, while incidence remained
      stable during the period. Hemodialysis was the predominant initial modality
      (89%). The patients were majority male with mean age 53 years, residents of the
      Southeast region and presented unknown causes as the main cause of chronic renal
      disease, followed by hypertension, diabetes and glomerulonephritis. Of these
      patients, 42% progressed to death and 7% underwent kidney transplantation. The
      patients on peritoneal dialysis were older and had higher prevalence of diabetes.
      The death rate varied from 7% among transplanted patients to 45% among non
      transplanted patients. In the final Cox proportional hazards model, the risk of
      mortality was associated with increasing age, female sex, having diabetes, living
      in the North and Northeast region, peritoneal dialysis as a first modality and
      not having renal transplantation. CONCLUSIONS: There was an increased prevalence
      of patients on renal therapy in Brazil. Increased risk of death was associated
      with advanced age, diabetes, the female sex, residents of the North and Northeast
      region and lack of renal transplant.

PMID- 20676556
TI  - Recurrence of leprosy cases in the State of Mato Grosso, Central-West Brazil.
AB  - OBJECTIVE: To compare new registrations of recurrences of leprosy cases in
      primary healthcare units (PHUs) and in specialized units in the State of Mato
      Grosso. METHODS: This was a cross-sectional study based on all new registrations
      (N = 323) of recurrences of leprosy cases within the Notifiable Disease
      Information System (SINAN) between 2004 and 2006 that were made in the State of
      Mato Grosso, Central-West Brazil. The cases diagnosed were compared regarding
      sex, age, clinical-laboratory characteristics and geographical distribution among
      the municipalities. To compare and calculate the proportions of the variables,
      the chi-square test at the significance level of 5% was used. RESULTS: Among the
      new registrations of recurrences, 20% were confirmed at specialized units and 80%
      at PHUs. However, most of the diagnoses at PHUs presented negative bacilloscopy
      findings (c2 = 12.34; p = 0.002). Seventy-one per cent of the cases were among
      males; the mean age was 43 years. No differences in the percentages of
      registrations were observed between the healthcare units with regard to clinical
      form, operational classification or degree of physical incapacity. Out of the
      total number of municipalities in the state, 64.7% presented recurrences and
      these accounted for 6 to 20% of all registrations. CONCLUSIONS: The new
      registrations of cases of recurrence in Mato Grosso were influenced by the
      diagnoses made at PHUs, thus suggesting that there is a deficiency within the
      healthcare services in recognizing cases of recurrence.

PMID- 20676557
TI  - Validity of the WHO VAW study instrument for estimating gender-based violence
      against women.
AB  - OBJECTIVE: To validate the instrument of the World Health Organization Violence
      Against Women (WHO VAW) study on psychological, physical and sexual violence
      against women perpetrated by intimate partners. METHODS: This was a cross
      sectional study conducted in several countries between 2000 and 2003, including
      Brazil. Representative random samples of women aged 15-49 years with intimate
      partners were selected, living in the city of Sao Paulo (n = 940) and in the Zona
      da Mata, Pernambuco (n = 1,188), southeastern and northeastern regions,
      respectively. Exploratory factor analysis on questions relating to violence was
      performed (four psychological, six physical and three sexual questions), with
      varimax rotation and creation of three factors. Cronbach's alpha was calculated
      to analyze the internal consistency. To validate through extreme groups, mean
      scores (0 to 13 points) for violence were tested in relation to the following
      outcomes: self-rated health, daily activities, presence of discomfort or pain,
      suicidal ideation or attempts, heavy alcohol consumption and presence of common
      mental disorders. RESULTS: Three factors were defined, with similar accumulated
      variance (0.6092 in Sao Paulo and 0.6350 in the Zona da Mata). For Sao Paulo, the
      first factor was determined by physical violence, the second by sexual violence
      and the third by psychological violence. For the Zona da Mata, the first factor
      was formed by psychological violence, the second by physical violence and the
      third by sexual violence. Cronbach's alpha coefficients were 0.88 in Sao Paulo
      and 0.89 in the Zona da Mata. The mean scores for violence were significantly
      higher for less favorable outcomes, with the exception of suicide attempts in Sao
      Paulo. CONCLUSIONS: The instrument was shown to be adequate for estimating gender
      based violence against women perpetrated by intimate partners and can be used in
      studies on this subject. It has high internal consistency and a capacity to
      discriminate between different forms of violence (psychological, physical and
      sexual) perpetrated in different social contexts. The instrument also
      characterizes the female victim and her relationship with the aggressor, thereby
      facilitating gender analysis.

PMID- 20676558
TI  - Physical intimate partner violence during gestation as a risk factor for low
      quality of prenatal care.
AB  - OBJECTIVE: To evaluate physical intimate partner violence during gestation as an
      independent risk factor for low quality of prenatal care. METHODS: A cross
      sectional study was carried out at three public maternity wards of the
      municipality of Rio de Janeiro (Southeastern Brazil). The 528 puerperal women
      included in the study were selected by simple random sampling from all babies
      born at term in 2000. Prenatal care information was collected through the
      pregnant woman's card and face-to-face interviews. The Kotelchuck index was
      employed to assess the quality of prenatal care. In order to identify violence
      situations, the Brazilian version of the instrument Revised Conflict Tactics
      Scales was used. Non-conditional logistic regression was used to assess the
      effect of exposure, after controlling for confounding variables. RESULTS: Even
      after adjustment for socioeconomic, demographic, reproductive, and couple's
      lifestyle variables, physical intimate partner violence during gestation remained
      associated with low quality of prenatal care. Women exposed to physical violence
      during gestation had 2.2 times more chance of presenting inadequate prenatal care
      compared to those without history of physical violence. CONCLUSIONS: These
      findings point to the need of identifying family conflict situations since the
      beginning of prenatal care in order to address the issue and enable higher
      adherence to follow-up among victimized pregnant women.

PMID- 20676559
TI  - Fruit and vegetable intake by adults in Ribeirao Preto, Southeastern Brazil.
AB  - OBJECTIVE: To assess fruit and vegetable intake by adults and identify
      sociodemographic and life style variables associated with this intake. METHODS: A
      population-based cross-sectional study was performed in the urban area of the
      city of Ribeirao Preto, Southeastern Brazil, in 2006. Sample was selected using
      three-stage cluster sampling, with census tracts as primary units. Sample was
      comprised of 930 participants aged 30 years and more and the design effect was
      considered in data analysis. Fruit and vegetable intake was based on a semi
      quantitative food frequency questionnaire, using mean scores of frequency of
      fruit and vegetable intake, daily intake and minimum intake of such foods as
      indicators. The independent variables analyzed were as follows: age group,
      marital status, level of education, per capita household income, nutritional
      status, smoking and physical activity. Mean scores of frequency of intake were
      estimated by point and 95% confidence intervals. Prevalence ratios were also
      estimated by point and 95% confidence intervals to analyze association, using
      Poisson regression. Linear trend tests were applied, adopting a 5% confidence
      level. RESULTS: Only 24% of men and 38% of women met the minimum recommendation
      for fruit and vegetable intake; there was a positive association with age and per
      capita income. Women with a higher level of education and men who lived with a
      female partner consumed more fruits and vegetables than others. Physical
      activity, smoking and nutritional status were not associated with the minimum
      recommended fruit and vegetable intake. CONCLUSIONS: Socioeconomic factors have
      an important influence on fruit and vegetable intake and, as these are subject to
      intervention, they can contribute to the adoption of healthy eating habits.

PMID- 20676560
TI  - Social inequality and exposure to magnetic fields in the metropolitan region of
      Sao Paulo, Southeastern Brazil.
AB  - OBJECTIVE: To estimate the prevalence of exposure to magnetic fields generated by
      transmission lines (TL) and characterize the exposed population. METHODS:
      Information about TL in the metropolitan region of Sao Paulo, Southeastern
      Brazil, was provided by the electricity companies and mapped out using geographic
      information system (GIS). Demographic and socioeconomic data were obtained from
      the 2000 Census and added to the GIS in another layer. Households and their
      inhabitants that were located at a distance from the TL that was sufficient to
      generate a magnetic field 0.3 microT (microteslas) were deemed to be exposed. The
      prevalence was estimated according to the area of the corridors of exposure along
      the TL. Two approaches were used to delimit the corridor width: one consisted of
      widths that were predefined by the TL voltage, and the other consisted of
      calculation of the magnetic field. The socioeconomic information on the exposed
      and non-exposed populations were compared by applying the two-proportion test
      (alpha= 5%). RESULTS: In the corridors with predefined widths, the prevalence of
      exposure was 2.4%, and in the calculated corridors, the prevalence was 1.4%. Both
      methods indicated higher prevalence of exposure among the younger population, and
      among individuals with lower education and income levels (p < 0.001).
      CONCLUSIONS: The prevalence of exposure to magnetic fields generated by TL in the
      metropolitan region of Sao Paulo was lower than what has been observed in other
      countries. The results indicate inequality in the exposure to magnetic fields in
      this urban area, with greater risk to vulnerable populations such as children and
      socioeconomically less favored individuals.

PMID- 20676561
TI  - Psychosocial factors of work and mental disorders in electricians.
AB  - OBJECTIVE: To identify psychosocial aspects of work associated with common mental
      disorders in workers who maintain electrical transmission lines and equipment.
      METHODS: A cross-sectional study was performed with 158 workers in the
      maintenance sector of an electric power company, in Northeastern Brazil. The main
      independent variable were the psychosocial aspects of work, measured according to
      the demand-control model (passive job, active job, low-strain job, and high
      strain job), while the dependent variable was the prevalence of common mental
      disorders, measured by the Self-Reporting Questionnaire (SRQ-20). The
      relationships between variables were analyzed in multiple logistic regression
      models, considering a 5% significance level. RESULTS: The prevalence of common
      mental disorders was 20.3%, varying according to the four categories of the
      demand-control model. The high-strain job group showed a prevalence that was 2.7
      times higher than that of the low-strain job group, after adjustment for the
      "physical activity practice", "leisure", "level of education" and "social
      support" covariables. CONCLUSIONS: The prevalence of common mental disorders was
      associated with psychosocial aspects present in the work of electricians,
      especially high-strain jobs, in addition to high psychological demand and low
      social support.

PMID- 20676562
TI  - Health-related quality of life and working conditions among nursing providers.
AB  - OBJECTIVE: To evaluate working conditions associated with health-related quality
      of life (HRQL) among nursing providers. METHODS: Cross-sectional study conducted
      in a university hospital in the city of Sao Paulo, Southeastern Brazil, during
      2004-2005. The study sample comprised 696 registered nurses, nurse technicians
      and nurse assistants, predominantly females (87.8%), who worked day and/or night
      shifts. Data on sociodemographic information, working and living conditions,
      lifestyles, and health symptoms were collected using self-administered
      questionnaires. The following questionnaires were also used: Job Stress Scale,
      Effort-Reward Imbalance (ERI) and Medical Outcomes Study 36-Item Short-Form
      Health Survey (SF-36). Ordinal logistic regression analysis using proportional
      odds model was performed to evaluate each dimension of the SF-36. RESULTS: Around
      22% of the sample was found to be have high strain and 8% showed an effort-reward
      imbalance at work. The dimensions with the lowest mean scores in the SF-36 were
      vitality, bodily pain and mental health. High-strain job, effort-reward imbalance
      (ERI>1.01), and being a registered nurse were independently associated with low
      scores on the role emotional dimension. Those dimensions associated to mental
      health were the ones most affected by psychosocial factors at work. CONCLUSIONS:
      Effort-reward imbalance was more associated with health than high-strain (high
      demand and low control). The study results suggest that the joint analysis of
      psychosocial factors at work such as effort-reward imbalance and demand-control
      can provide more insight to the discussion of professional roles, working
      conditions and HRQL of nursing providers.

PMID- 20676563
TI  - Seroprevalence of herpes simplex 1-2 antibodies in Brazil.
AB  - OBJECTIVE: To estimate the seroprevalence of HSV-1 and HSV-2 antibodies in Brazil
      and to analyze factors associated. METHODS: Cross-sectional study including
      subjects aged 1-40 years from the general population in four different
      geographical areas in Brazil between 1996 and 1997. All subjects were stratified
      by age and gender and 1,090 of them were included in the final analysis. Blood
      samples were tested for HSV-1 and HSV-2 antibodies by type-specific (gG1 and gG2)
      ELISA. Frequencies and proportions were described and compared among groups using
      two-sided Fisher's exact test. A logistic regression analysis was performed to
      assess the influence of the variables age, gender, geographical area,
      socioeconomic condition, past history of STD, seropositivity for anti-HSV-1 or
      anti-HSV-2 and interactions of any of these factors on the seroprevalence of HSV
      1 and/or HSV-2. RESULTS: The age-adjusted seroprevalences of HSV-1 and HSV-2
      antibodies were 67.2% and 11.3%, respectively, without sex differences and being
      higher in the North region. Seroprevalences increased with age and, for HSV-2
      infection, the higher increase was observed among adolescents and young adults.
      Subjects who tested positive for HSV-1 were more likely to also test positive for
      HSV-2 (15.7%) compared to HSV-1 negative subjects (4.7%). In the multivariate
      analysis past history of STD significantly (OR=3.2) increased the likelihood of
      HSV-2 infection whereas socioeconomic condition did not affect the results.
      CONCLUSIONS: HSV-1 and HSV-2 seroprevalences vary with age and among Brazilian
      regions. Past history of STD is a major risk factor for HSV-2 infection.

PMID- 20676564
TI  - Quality of life and adherence to HAART in HIV-infected patients.
AB  - A review on adherence to highly active antiretroviral therapy and the quality of
      life of patients living with HIV in the scientific literature, indexed in MEDLINE
      between 1998 and 2008, was performed. Studies published in Portuguese, Spanish or
      English with patients over 18 years of age were included. Reviews, case reports
      and letters were excluded. Of the 21 studies found, 12 were included (three
      clinical trials, three prospective cohorts and six cross-sectional studies). The
      relationship between quality of life and treatment adherence remains
      controversial, despite descriptive studies indicating the possibility of a
      positive association. The results may have been influenced by the specific
      characteristics of the described clinical trials and do not show a consensus
      regarding the impact of treatment adherence on patients' quality of life.

PMID- 20676565
TI  - Suicide in elderly people: a literature review.
AB  - A literature review was carried out focusing on the main factors associated with
      suicidal ideation, attempts and completed suicide in elders. The following
      databases were searched: MEDLINE, PsychINFO, SciELO and Biblioteca Virtual em
      Violencia e Saude da BIREME (BIREME's Violence and Health Virtual Library),
      referring to the period from 1980 to 2008. Fifty-two references were selected and
      analyzed. They showed a strong relationship among suicide ideation, attempt and
      completion in elderly individuals, which results from the interaction of complex
      physical, mental, neurobiological and social factors. Suicide associated with
      depression in the elderly can be prevented, provided the person is properly
      treated. In Brazil, it is necessary to invest in research, given the persistent
      increase in suicide rates among aged people, especially among males.

PMID- 20676566
TI  - Normative discourses on the desire to have children.
AB  - Reflections on normative discourses on sexuality, family and reproduction are
      shown, promoted by medical and juridical knowledge in modern society. This study
      was based on the assumption that changes and maintenance of values and practices
      coexist in the current discourses on the desire to have children, expressed as
      claims in the dimension of sexual and reproductive rights, with new demands in
      the sphere of public and health policies. The current value attributed to family
      is founded on the model of modern conjugal family, which can be observed in the
      changes that have occurred in family relations and sexual identities. Based on a
      new configuration of values, the expectation of paternity and maternity has
      partly become a value of the homosexual relationship. However, despite changes in
      the sphere of family relations and social identities, the centrality of the
      heterosexual couple prevails in the medical and juridical discourse on the desire
      to have children.

PMID- 20676567
TI  - [Cell therapy and stem cells research funding in Brazil].

PMID- 20676568
TI  - Professor Adib Jatene, a youth of 80 years.

PMID- 20676569
TI  - Suggestions for how academia can improve the health of medicine.

PMID- 20676570
TI  - Detection of Streptococcus agalactiae colonization in pregnant women by using
      combined swab cultures: cross-sectional prevalence study.
AB  - CONTEXT AND OBJECTIVE: Maternal Streptococcus agalactiae colonization and early
      onset neonatal sepsis have aroused interest in the worldwide literature.
      Streptococcal neonatal disease is associated with significant morbidity and
      mortality in the perinatal period, especially among premature neonates. The aim
      of this study was to assess the prevalence of maternal streptococcal colonization
      by using combined swab cultures, compared with swab collection from a single
      site. DESIGN AND SETTING: Cross-sectional study at Faculdade de Medicina de
      Botucatu, Universidade Estadual Paulista. METHODS: Samples were obtained from 405
      patients at gestational ages of 35 to 37 weeks. Swabs from the perianal (rectal)
      region, vaginal introitus and upper lateral vaginal vault were cultured in Todd
      Hewitt selective broth. Colonies suggestive of Streptococcus agalactiae were
      subjected to the catalase and CAMP (Christie, Atkins, Munch-Petersen) tests. To
      evaluate the positivity of combined swab cultures, Tukey's test was used for
      comparison of proportions. RESULTS: The prevalence of streptococcal colonization
      was 25.4%. Among the patients with positive cultures, 28.1% had this at only one
      collection site, 24.2% simultaneously at two sites and 47.5% at all three sites.
      Associating the swabs from two collection sites significantly increased
      streptococcal isolation, compared with a single swab (P < 0.05), except for
      perianal (rectal) collection. Use of combined swabs from three collection sites
      showed statistically higher isolation rates. CONCLUSION: In combined swab
      cultures collected from three collection sites, the prevalence of maternal
      Streptococcus agalactiae colonization was higher than in swabs collected from a
      single site.

PMID- 20676571
TI  - Correlations between radiographic, magnetic resonance and histological
      examinations on the degeneration of human lumbar intervertebral discs.
AB  - CONTEXT AND OBJECTIVE: There is controversy regarding which imaging method is
      best for identifying early degenerative alterations in intervertebral discs. No
      correlations between such methods and histological finds are presented in the
      literature. The aim of this study was to correlate the thickness of
      intervertebral discs measured on simple radiographs with the degree of
      degeneration seen on magnetic resonance images and the histological findings
      relating to nerve ends inside the discs. DESIGN AND SETTING: Cross-sectional
      correlation study on the lumbar spines of human cadavers, at Universidade Federal
      de Sao Paulo (Unifesp), Sao Paulo, Brazil. METHODS: Ten lumbar spinal columns
      were extracted from human cadavers and subjected to magnetic resonance imaging
      and simple radiography. They were classified according to the degree of disc
      degeneration seen on magnetic resonance, and the thickness of the discs was
      measured on radiographs. The intervertebral discs were then extracted, embedded
      in paraffin and analyzed immunohistochemically with protein S100, and the nerve
      fibers were counted and classified. RESULTS: No correlation was observed between
      the thickness of the intervertebral discs and the degree of degeneration seen on
      magnetic resonance images. Only the uppermost lumbar discs (L1/L2 and L2/L3)
      presented a correlation between their thickness and type I and IV nerve endings.
      CONCLUSION: Reduced disc thickness is unrelated to increased presence of nerve
      ends in intervertebral discs, or to the degree of disc degeneration.

PMID- 20676572
TI  - Prevalence of scoliosis among school students in a town in southern Brazil.
AB  - CONTEXT AND OBJECTIVE: Scoliosis is not a diagnosis, but a description of a
      structural alteration that occurs in a variety of conditions. Progression of the
      curvature during periods of rapid growth may result in severe deformity, which
      may be accompanied by cardiopulmonary compromise. This study had the aims of
      measuring the prevalence of scoliosis among students in the fifth to eighth
      school years and investigating possible associations between the presence of
      scoliosis, body overweight and the weight of school materials. DESIGN AND
      SETTING: Analytical cross-sectional study developed in the municipality of Carlos
      Barbosa, Rio Grande do Sul, Brazil. METHODS: A total of 1340 students were
      evaluated. The variables studied were the prevalence of scoliosis, type of
      school, location of the school, age, school year, sex, body weight, prevalence of
      excessive school material weight, height, body mass index (BMI) and spinal
      alignment measurements. RESULTS: The prevalence of scoliosis was 1.4%; shoulder
      and scapula asymmetry, 6.6%; forearm and trunk asymmetry, 4.0%; spinal
      misalignment, 1.9%; Thales triangle asymmetry, 6.4%; body overweight, 19.8%; and
      carrying of excessively heavy school materials, 27%. The study did not find any
      statistically significant association between scoliosis and body overweight, or
      between scoliosis and excessive weight of school materials. CONCLUSIONS: The
      prevalence of scoliosis in this school-based sample was low. No correlation was
      found between this clinical condition and the other variables.

PMID- 20676573
TI  - The experience of infectologists faced with death and dying among their patients
      over the course of the AIDS epidemic in the city of Sao Paulo: qualitative study.
AB  - CONTEXT AND OBJECTIVE: With the emergence of the acquired immunodeficiency
      syndrome (AIDS) in 1981, infectologists' care practices went through great
      changes. The objective of this study was to describe and analyze the experiences
      of infectologists in dealing with death and dying among their patients, over the
      course of the AIDS epidemic in the city of Sao Paulo. DESIGN AND SETTING: A
      qualitative approach was used. Twenty infectologists from five hospitals that
      treat human immunodeficiency virus (HIV)/AIDS patients in the municipality of Sao
      Paulo were interviewed. METHODS: The sample was formed through the snowball
      process. The sample size was determined using the saturation criterion. To
      analyze the material obtained from the interviews, the procedure of thematic
      analysis was used. This consisted of finding the core meaning relating to the
      study objective, within the set of materials obtained. RESULTS: Analysis of the
      material obtained from the interviews led to three main themes: 1. The initial
      context of AIDS and its impact on infectologists; 2. Modifications to the
      infectologists' attachments to patients after the introduction of highly active
      antiretroviral therapy (HAART); 3. Coping with death and dying. CONCLUSIONS: This
      study shows the importance of considering the distress, emotional overload and
      adaptive mechanisms relating to death and dying among patients, both in training
      and in professional practice.

PMID- 20676574
TI  - Incidence trend for breast cancer among young women in Goiania, Brazil.
AB  - CONTEXT AND OBJECTIVE: It has been suggested that there has been a large increase
      in breast cancer incidence among young women over the last decade. The aim of
      this study was to describe the incidence of breast cancer among young women up to
      39 years of age in Goiania, between 1988 and 2003, and to compare this with other
      age groups. DESIGN AND SETTING: Retrospective study using the database of the
      Population-based Cancer Registry of Goiania, State of Goias, Brazil. METHODS: The
      incidence was calculated according to age groups: up to 39 years, 40 to 59 years
      and 60 years and over. Average annual percentage changes (AAPCs) were estimated
      for the different age groups using Poisson regression. RESULTS: Over this period,
      3,310 new cases were recorded. The standardized incidence was 2.89/100,000 in
      1988 and increased to 6.37/100,000 in 2003 (R(2) = 0.52) for the group aged up to
      39 years (p < 0.003). For the group from 40 to 59 years old, the incidence was
      14.39/100,000 in 1988 and 41.70/100,000 in 2003 (R(2) = 0.85; p < 0.001). For the
      group aged 60 years and over, it was 17.62/100,000 and 28.49/100,000,
      respectively (R(2) = 0.67; p < 0.001). The AAPCs were 5.22%, 5.53% and 4.54% for
      the age groups up to 39, 40 to 59 and 60 years and over, respectively.
      CONCLUSIONS: The incidence of breast cancer among young women in Goiania has been
      increasing significantly, although this change was similar to the increase in
      other age groups.

PMID- 20676575
TI  - Methodological adequacy of articles published in two open-access Brazilian
      cardiology periodicals.
AB  - CONTEXT AND OBJECTIVE: The use of rigorous scientific methods has contributed
      towards developing scientific articles of excellent methodological quality. This
      has made it possible to promote their citation and increase the impact factor.
      Brazilian periodicals have had to adapt to certain quality standards demanded by
      these indexing organizations, such as the content and the number of original
      articles published in each issue. This study aimed to evaluate the methodological
      adequacy of two Brazilian periodicals within the field of cardiology that are
      indexed in several databases and freely accessible through the Scientific
      Electronic Library Online (SciELO), and which are now indexed by the Web of
      Science (Institute for Scientific Information, ISI). DESIGN AND SETTING:
      Descriptive study at Brazilian Cochrane Center. METHODS: All the published
      articles were evaluated according to merit assessment (content) and form
      assessment (performance). RESULTS: Ninety-six percent of the articles analyzed
      presented study designs that were adequate for answering the objectives.
      CONCLUSIONS: These two Brazilian periodicals within the field of cardiology
      published methodologically adequate articles, since they followed the quality
      standards. Thus, these periodicals can be considered both for consultation and as
      vehicles for publishing future articles. For further analyses, it is essential to
      apply other indicators of scientific activity such as bibliometrics, which
      evaluates quantitative aspects of the production, dissemination and use of
      information, and scientometrics, which is also concerned with the development of
      science policies, within which it is often superimposed on bibliometrics.

PMID- 20676576
TI  - Diagnostic accuracy of sonography for pleural effusion: systematic review.
AB  - CONTEXT AND OBJECTIVE: The initial method for evaluating the presence of pleural
      effusion was chest radiography. Isolated studies have shown that sonography has
      greater accuracy than radiography for this diagnosis; however, no systematic
      reviews on this matter are available in the literature. Thus, the aim of this
      study was to evaluate the accuracy of sonography in detecting pleural effusion,
      by means of a systematic review of the literature. DESIGN AND SETTING: This was a
      systematic review with meta-analysis on accuracy studies. This study was
      conducted in the Department of Diagnostic Imaging and in the Brazilian Cochrane
      Center, Discipline of Emergency Medicine and Evidence-Based Medicine, Department
      of Medicine, Universidade Federal de Sao Paulo (Unifesp), Sao Paulo, Brazil.
      METHOD: The following databases were searched: Cochrane Library, Medline, Web of
      Science, Embase and Literatura Latino-Americana e do Caribe em Ciencias da Saude
      (Lilacs). The references of relevant studies were also screened for additional
      citations of interest. Studies in which the accuracy of sonography for detecting
      pleural effusion was tested, with an acceptable reference standard (computed
      tomography or thoracic drainage), were included. RESULTS: Four studies were
      included. All of them showed that sonography had high sensitivity, specificity
      and accuracy for detecting pleural effusions. The mean sensitivity was 93% (95%
      confidence interval, CI: 89% to 96%), and specificity was 96% (95% CI: 95% to
      98%). CONCLUSIONS: In different populations and clinical settings, sonography
      showed consistently high sensitivity, specificity and accuracy for detecting
      fluid in the pleural space.

PMID- 20676577
TI  - A new therapeutic proposal for writer's cramp: a case report.
AB  - CONTEXT: Writer's cramp is a kind of focal hand dystonia that appears when
      individuals are writing. Since pharmacological treatment has not shown the
      desired therapeutic response, a study on immobilization of the damaged
      musculature was performed on two individuals with writer's cramp, using splints
      with the objective of reducing the handwriting abnormalities. CASE REPORT: Two
      patients presenting writer's cramp who had previously undergone different
      therapies, including botulinum toxin, without an adequate response, participated
      in a body awareness program, followed by immobilization of the hand musculature
      damaged by dystonia, by means of splints, with handwriting training. At the end
      of the procedure, objective and subjective improvements in the motor pattern of
      writing could be observed. The immobilization of the dystonic musculature of the
      hand by means of splints and the motor training of handwriting helped to improve
      and consequently to reduce the dystonic component observed in the writer's cramp.

PMID- 20676578
TI  - Fibular dimelia and mirror polydactyly of the foot in a girl presenting
      additional features of the VACTERL association.
AB  - CONTEXT: The association between fibular dimelia and mirror polydactyly of the
      foot is considered to be a very rare lower-limb abnormality. On the other hand,
      VACTERL is an acronym for a nonrandom association of congenital anomalies for
      which the etiology is still poorly understood. CASE REPORT: The patient was a
      seven-month-old white girl whose mother had used misoprostol in the second month
      of pregnancy to induce abortion. On clinical evaluation, she was small for her
      age and presented hypotonia, anteverted nares, long philtrum and carp-like mouth.
      Her left hand had a reduction defect, with absence of the extremities of the
      second, third and fifth fingers and camptodactyly of the fourth finger. The
      ipsilateral lower limb presented significant shortening, especially rhizomelic
      shortening. Her left foot had a mirror configuration with seven toes and no
      identifiable hallux. The pelvis was hypoplastic. Esophageal atresia with
      tracheoesophageal fistula and imperforate anus were detected during the neonatal
      period. Abdominal ultrasound identified agenesis of the right kidney and left
      pyelocaliceal duplication. Radiographic evaluation on the left side showed iliac
      and femoral hypoplasia, absence of the tibia with a duplicated fibula and seven
      metatarsals and toes with no identifiable hallux on the foot. Echocardiography
      demonstrated an atrial septal defect. Based on the literature, we believe that
      the spectrum of malformations presented by our patient may be related to the
      vascular disruptive effect of the misoprostol. However, we cannot rule out the
      possibility that this association might simply be a coincidence.

PMID- 20676579
TI  - Negative correlations between anxiety-depressive symptoms and quality of life
      among patients on hemodialysis.

PMID- 20676580
TI  - The Cochrane Collaboration and the World Health Organization: new perspectives
      for an old relationship.

PMID- 20676583
TI  - Suspicion of obstructive sleep apnea by Berlin Questionnaire predicts events in
      patients with acute coronary syndrome.
AB  - BACKGROUND: From a mechanistic standpoint, obstructive sleep apnea (OSA) may
      further disturb cardiovascular homeostasis in the setting of acute coronary
      syndrome (ACS). OBJECTIVE: We sought to investigate if a standardized clinical
      diagnosis of OSA, in acute coronary syndrome patients, predicts the risk of
      cardiovascular events during hospitalization. METHODS: In a prospective cohort
      study, a group of 200 patients diagnosed with ACS between September 2005 and
      November 2007 were stratified by the Berlin Questionnaire (BQ) regarding the risk
      for OSA (high or low risk). We tested if the subgroup of high risk for OSA was
      prone to a higher frequency of cardiovascular events. The primary endpoint
      evaluated was a composite outcome of cardiovascular death, recurrent cardiac
      ischemic events, acute pulmonary edema and stroke during hospitalization.
      RESULTS: Ninety four (47%) patients assessed by the BQ were likely to have OSA.
      High risk for OSA was associated with a non-significant higher mortality (4.25%
      vs 0.94%; p=0.189), but a significant higher incidence of composite
      cardiovascular events (18.08% vs 6.6%; p=0.016). In the logistic regression
      model, multivariate predictors of composite cardiovascular events were age (OR=
      1.048; 95% CI 1.008 to 1.090; p=0.019), left ventricular ejection fraction (OR=
      0.954; 95% CI 0.920 to 0.989; p=0.010), and higher risk for OSA (OR= 3.657; 95%
      CI 1.216 to 10.996; p=0.021). CONCLUSION: The use of a simple and validated
      questionnaire (BQ) to identify patients with higher risk for OSA may help in the
      prediction of cardiovascular outcome during hospitalization. Moreover, our data
      suggests that OSA is very common in patients with ACS.

PMID- 20676584
TI  - Comparison of the different definition criteria for the diagnosis of the
      metabolic syndrome in elderly women.
AB  - BACKGROUND: The criteria for best defining the metabolic syndrome (MS),
      especially in the elderly population, are still little known, and the
      understanding is increasingly necessary. OBJECTIVE: Compare the four MS
      definition proposals, two official ones (National Cholesterol Education Program's
      Adult Treatment Panel III/NCEP-ATPIII and International Diabetes Federation/IDF)
      and two proposed definitions (Metabolic Syndrome - National Cholesterol Education
      Program's Adult Treatment Panel III - modified/MS-ATPM and Metabolic Syndrome -
      International Diabetes Federation - modified/MS-IDFM), derived from the changes
      in the official criteria. METHODS: A total of 113 women (60-83 years old)
      participated in this study; they were submitted to anthropometric, blood
      pressure, lipid profile, fasting glycemia tests and answered questions related to
      life style habits and health conditions. Statistical analyses were performed
      using the chi-square test and Kappa coefficient determination. RESULTS: The
      frequency of the high pressure levels was similar in the two official definitions
      (54.8%), with a reduction in the two proposed definitions (33.6%). The
      homeostasis change of the glucose was higher as per the IDF and MS-IDFM (30.1%).
      The hypertriglyceridemia and the low levels of HDL-c were similar in all the
      definitions (35.4%). In relation to the abdominal obesity, the higher occurrence
      was registered by the IDF criteria (88.5%). The presence of the metabolic
      syndrome presented higher and lower frequencies as per the IDF proposal (45.1%)
      and MS-IDFM (22.1%), respectively. Higher agreement was found between the
      modified definition MS-ATPM with NCEP-ATPIII and MS-IDFM (Kappa: 0.79 and 0.77; p
      < 0.00001). CONCLUSION: The MS-ATPM proposal was found more adequate for the MS
      detection in the evaluated elderly women.

PMID- 20676585
TI  - Ethics in research with human beings: from knowledge to practice.
AB  - BACKGROUND: In Brazil, resolution 196/96 and its amendments regulate the
      preservation of rights, respect and dignity of human beings involved in research.
      OBJECTIVE: To analyze the adequacy of Free Communications (FC) presented during
      the XVIII Congresso Pernambucano de Cardiologia to resolution 196/96. METHODS:
      During a cross-sectional study, interviews were carried out with the authors of
      the FC presented at the Congress and the abstracts of the studies were assessed
      in order to identify the need for previous approval by a Research Ethics
      Committee (REC). RESULTS: A total of 90 FC were presented and, in most of them
      (86.8%), medical files were the most commonly used source of data. Only 23.1% of
      the FC were submitted to the assessment of a REC and 15.4% of them used a Free
      and Informed Consent Form (FICF). Among the authors whose studies were not
      assessed by a REC, 65.6% stated that this conduct was not necessary and 18% of
      them were unaware of the need to submit the study to such assessment. The written
      authorization given by the institution where the FC were carried out was not
      obtained in 56.6% of the studies. Most of the authors (80.0%) stated that they
      had never read Resolution 196/96. The proportion of FC submitted to a REC was
      significantly higher among authors that had read Resolution 196/96 (p = 0.005).
      The FC design influenced the non-submission of the studies to a REC (p < 0.001).
      Most of the FC that were authorized by the institution where they were carried
      out were submitted to a REC (p < 0.001). CONCLUSION: Most of the FC presented at
      the Congress did not follow the Brazilian regulations concerning the ethics in
      research.

PMID- 20676586
TI  - Evaluation of the metabolism of high energy phosphates in patients with Chagas'
      disease.
AB  - BACKGROUND: Abnormalities in myocardial metabolism have been observed in patients
      with heart failure of different etiologies. Magnetic resonance spectroscopy (MRS)
      with phosphorus-31 is a noninvasive technique that allows detection of myocardial
      metabolic changes. OBJECTIVE: To determine the resting metabolism of high-energy
      phosphates in patients with Chagas' disease (CD) by MRS with phosphorus-31.
      METHODS: We studied 39 patients with CD, 23 with preserved ventricular function
      (PF Group) and 16 with ventricular dysfunction (VD Group), assessed by Doppler
      echocardiography. MRS of the anterosseptal region was performed in 39 patients
      and 8 normal subjects (C Group) through a Phillips 1.5 Tesla device, obtaining
      the phosphocreatine/beta-adenosine triphosphate myocardial ratio (PCr/beta-ATP).
      RESULTS: The levels of cardiac PCr/beta-ATP were reduced in VD Group in relation
      to PF Group, and the latter presented reduced levels compared to C Group (VD
      Group: 0.89 +/- 0.31 vs PF Group: 1.47 +/- 0.34 vs C Group: 1.88 +/- 0.08, p <
      0.001). A correlation was found between left ventricular ejection fraction and
      PCr/beta-ATP in 39 patients (r = 0.64, p < 0.001). Patients under functional
      class I (n = 22) presented PCr/beta-ATP of 1.45 +/- 0.35, and those in functional
      classes II and III (n = 17), PCr/beta-ATP of 0.94 +/- 0.36 (p < 0.001).
      CONCLUSION: The 31-phosphorus MRS was able to detect non-invasively changes in
      the rest energy metabolism of patients with Chagas' disease, with and without
      systolic dysfunction. These changes were related to the severity of heart
      impairment.

PMID- 20676587
TI  - Rosiglitazone and vascular injury in hypercholesterolemic rabbits: neointimal
      formation assessment.
AB  - BACKGROUND: Rosiglitazone has been the focus of extensive discussion. OBJECTIVE:
      To evaluate the effects of rosiglitazone on iliac arteries, both at the injury
      site and the contralateral artery, of hypercholesterolemic rabbits undergoing
      balloon catheter injury. METHODS: White male rabbits were fed a
      hypercholesterolemic diet by oral gavage for 6 weeks and divided into two groups
      as follows: rosiglitazone group (14 rabbits treated with rosiglitazone during 6
      weeks) and the control group (18 rabbits without rosiglitazone). Animals
      underwent balloon catheter injury of the right iliac artery on the 14th day.
      RESULTS: In the contralateral iliac artery, there was no significant difference
      in the intima/media layer area ratio (IMR) between the control and rosiglitazone
      groups. Rosiglitazone did not reduce the probability of type I, II, or III
      lesions (72.73% vs 92.31%; p=0.30) and type IV or V lesions (27.27% vs 7.69%;
      p=0.30). As for the homolateral iliac artery, the intimal area was significantly
      lower in the rosiglitazone group, as compared to the control group (p = 0.024).
      The luminal layer area was higher in the rosiglitazone group vs. the control
      group (p < 0.0001). There was a significant reduction of 65% in the IMR in the
      rosiglitazone group vs the control group (p = 0.021). None of the histological
      criteria for type I-V atherosclerotic lesions (American Heart Association) were
      found in the homolateral iliac artery. CONCLUSION: These findings demonstrate
      that rosiglitazone given for 6 weeks prevents atherogenesis at the injury site,
      but not in a vessel distant from the injury site.

PMID- 20676588
TI  - Association of physical training with beta-blockers in heart failure in mice.
AB  - BACKGROUND: Currently there are several types of interventions for the treatment
      of heart failure (HF). Among these are beta-blocker therapy (BB) and physical
      training (PT). However, the effects of the combination of these therapies are
      poorly studied. OBJECTIVE: To investigate the effects of BB treatment with
      metoprolol (M) and carvedilol (C) associated with PT in mice with HF. METHODS: We
      used a genetic model of sympathetic hyperactivity-induced heart failure in mice.
      Initially, we divided the HF animals into three groups: sedentary (S); trained
      (T); treated with M (138 mg/kg) (M); or C (65 mg/kg) (C). In the second part, we
      divided the groups into three subgroups: sedentary (S); trained and treated with
      M (TM); and trained and treated with C (CT). The PT consisted of aerobic training
      on a treadmill for 8 weeks. Exercise tolerance was assessed by maximal graded
      test, and fractional shortening (FS) was assessed by echocardiography.
      Cardiomyocyte diameter and collagen volume fraction were evaluated by
      histological analysis. Data were compared by one way ANOVA and post hoc Duncan
      test. The significance level was set at p <= 0.05. RESULTS: As to FS and cardiac
      remodeling, we found that, in isolation, T, M, and C showed an improvement of the
      variables analyzed. As to therapy combination, after the intervention period, we
      observed an increase in exercise tolerance in MT and CT (43.0% and 33.0%
      respectively). There was also a reduction in cardiomyocyte diameter (10.0% and
      9.0% respectively) and in collagen volume fraction (52.0% and 63.0%) after the
      intervention. However, only CT significantly improved FS. CONCLUSION: The
      association of PT with M or C therapies provided benefits on cardiac function and
      remodeling in HF mice.

PMID- 20676589
TI  - Brazilian academic search filter: application to the scientific literature on
      physical activity.
AB  - OBJECTIVE: To develop a search filter in order to retrieve scientific
      publications on physical activity from Brazilian academic institutions. METHODS:
      The academic search filter consisted of the descriptor "exercise" associated
      through the term AND, to the names of the respective academic institutions, which
      were connected by the term OR. The MEDLINE search was performed with PubMed on
      11/16/2008. The institutions were selected according to the classification from
      the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES) for
      interuniversity agreements. RESULTS: A total of 407 references were retrieved,
      corresponding to about 0.9% of all articles about physical activity and 0.5% of
      the Brazilian academic publications indexed in MEDLINE on the search date. When
      compared with the manual search undertaken, the search filter (descriptor +
      institutional filter) showed a sensitivity of 99% and a specificity of 100%.
      CONCLUSIONS: The institutional search filter showed high sensitivity and
      specificity, and is applicable to other areas of knowledge in health sciences. It
      is desirable that every Brazilian academic institution establish its "standard
      name/brand" in order to efficiently retrieve their scientific literature.

PMID- 20676590
TI  - Adult physical activity levels and associated factors in rural communities of
      Minas Gerais State, Brazil.
AB  - OBJECTIVE: To estimate the physical activity level and its association with
      sociodemographic factors in adults living in rural areas. METHODS: Cross
      sectional population study including 567 adults in two rural communities from the
      Jequitinhonha Valley, Southeastern Brazil, during the years of 2008 and 2009.
      Physical activity levels were assessed with the adapted long version of the
      International Physical Activity Questionnaire. A cut-off point of 150 minutes per
      week was used in the analyses for the domains: occupational, household, leisure
      and commuting. The sociodemographic factors studied were sex, skin color, age,
      marital status, education and self-reported health. Bivariate analysis (chi
      square test, p< 0.05) and multiple logistic regression analysis were performed.
      RESULTS: The prevalence of subjects practicing 150 min/wk or more of work related
      physical activity was 82.9% (95% CI: 77.8;88.0) of those currently working. The
      equivalent proportions for the other domains were: household 63.5% (95% CI: 59.6;
      67.4); leisure time 10.1% (95% CI: 7.6;12.6) and commuting 32.0% (95% CI:
      28.2;35.8%). Men were more active than women in leisure time, commuting and
      occupational domains, while women were more active in the household domain.
      Leisure time physical activity was more prevalent in younger subjects, those with
      higher levels of education and among those of black or mixed skin color.
      Commuting physical activity was more frequent among younger women and among men
      and women in excellent/good health. Men with higher level of schooling were less
      active in the commuting domain. CONCLUSIONS: The prevalence of physically active
      adults in this rural area was high, but the levels of leisure time physical
      activity were low and followed patterns similar to those observed in urban areas,
      in relation to age, sex and educational status.

PMID- 20676591
TI  - Spirometry standards and FEV1/FVC repeatability.

PMID- 20676592
TI  - Measuring the lung age of smokers.

PMID- 20676593
TI  - Oxygen saturation and pneumonia: a complement to current practice or another
      burden for the GP?

PMID- 20676594
TI  - Diagnosing pneumonia accurately in the community--is it necessary?

PMID- 20676595
TI  - [Living donor liver transplantation in adults].
AB  - The worldwide shortage of adequate donor organs implies that living donor liver
      transplantation represents a valuable alternative to cadaveric transplantation.
      In addition to the complex surgical procedure the correct identification of
      eligible donors and recipients plays a decisive role in living donor liver
      transplantation. Donor safety must be of ultimate priority and overrules all
      other aspects involved. In contrast to the slightly receding numbers in Europe
      and North America, in recent years Asian programs have enjoyed constantly
      increasing living donor activity. The experience of the past 15 years has clearly
      demonstrated that technical challenges of both bile duct anastomosis and venous
      outflow of the graft significantly influence postoperative outcome. While short
      term in-hospital morbidity remains increased compared to cadaveric
      transplantation, long-term survival of both graft and patient are comparable or
      even better than in deceased donor transplantation. Especially for patients
      expecting long waiting times under the MELD allocation system, living donor liver
      transplantation offers an excellent therapeutic alternative. Expanding the so
      called "Milan criteria" for HCC patients with the option for living donor liver
      transplantation is currently being controversially debated.

PMID- 20676596
TI  - [Erythema annulare centrifugum. A clinical reaction pattern].
AB  - Erythema annulare centrifugum (EAC) is a clinical reaction pattern and not a
      specific clinicohistologic entity. The clinical and histologic differential
      diagnosis of EAC should take at least three main disease groups into
      consideration, which are often classified under this disorder: (tumid) lupus
      erythematosus, spongiotic dermatitides, and pseudolymphomas.

PMID- 20676597
TI  - [28-year old female patient with respiratory insufficiency, elevated liver
      enzymes, pancytopenia and fever].
AB  - We report on a 28-year old female patient with fever and severe respiratory
      insufficiency requiring mechanical ventilation. Cytomegalovirus pneumonia was
      diagnosed by bronchoalveolar lavage, and antiviral therapy was initiated. However
      fever persisted and laboratory workup showed pancytopenia and elevated liver
      enzymes. Additional blood tests demonstrated a markedly elevated ferritin level
      and high concentrations of inflammatory cytokines. A diagnosis of hemophagocytic
      lymphohistiocytosis was made and immunosuppressive therapy was started. The
      patient's condition and laboratory values improved rapidly.

PMID- 20676598
TI  - Voluntary exercise at the expense of reproductive success in Djungarian hamsters
      (Phodopus sungorus).
AB  - Energy demands of gestation and lactation represent a severe challenge for small
      mammals. Therefore, additional energetic burdens may compromise successful
      breeding. In small rodents, food restriction, cold exposure (also in combination)
      and wheel running to obtain food have been shown to diminish reproductive
      outcome. Although exhibited responses such as lower incidence of pregnancy,
      extended lactation periods and maternal infanticide were species dependent, their
      common function is to adjust energetic costs to the metabolic state reflecting
      the trade-off between maternal investment and self-maintenance. In the present
      study, we sought to examine whether voluntary exercise affects reproduction in
      Djungarian hamsters (Phodopus sungorus), which are known for their high
      motivation to run in a wheel. Voluntary exercise resulted in two different
      effects on reproduction; in addition to increased infanticide and cannibalism,
      which was evident across all experiments, the results of one experiment provided
      evidence that free access to a running wheel may prevent successful pregnancy. It
      seems likely that the impact of voluntary wheel running on reproduction was
      associated with a reduction of internal energy resources evoked by extensive
      exercise. Since the hamsters were neither food-restricted nor forced to run in
      the present study, an energetic deficit as reason for infanticide in exercising
      dams would emphasise the particularly high motivation to run in a wheel.

PMID- 20676599
TI  - Variations of immune parameters in terrestrial isopods: a matter of gender, aging
      and Wolbachia.
AB  - Ecological factors modulate animal immunocompetence and potentially shape the
      evolution of their immune systems. Not only environmental parameters impact on
      immunocompetence: Aging is one major cause of variability of immunocompetence
      between individuals, and sex-specific levels of immunocompetence have also been
      frequently described. Moreover, a growing core of data put in light that
      vertically transmitted symbionts can dramatically modulate the immunocompetence
      of their hosts. In this study, we addressed the influence of gender, age and the
      feminising endosymbiont Wolbachia (wVulC) on variations in haemocyte density,
      total PO activity and bacterial load in the haemolymph of the terrestrial isopod
      Armadillidium vulgare. This host-symbiont system is of particular interest to
      address this question since: (1) wVulC was previously shown as immunosuppressive
      in middle-aged females and (2) wVulC influences sex determination. We show that
      age, gender and Wolbachia modulate together immune parameters in A. vulgare.
      However, wVulC, which interacts with aging, appears to be the prominent factor
      interfering with both PO activity and haemocyte density. This interference with
      immune parameters is not the only aspect of wVulC virulence on its host, as
      reproduction and survival are also altered.

PMID- 20676600
TI  - [Rehabilitation of Parkinson's patients with deep brain stimulation. Experiences
      of the Neurological Rehabilitation Center Godeshohe].
AB  - BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has
      become an important therapeutic option in patients with advanced Parkinson's
      disease (PD). An increasing number of patients are referred for hospital
      rehabilitation after initial programming. The role of further DBS and medication
      adjustments for this rehabilitation therapy is uncertain. METHODS: This study was
      a retrospective analysis of a hospital rehabilitation program with a systematic
      algorithm to improve DBS efficacy in PD patients referred within 3 months after
      electrode implantation. This study analyzed (1) changes of stimulation parameters
      and medication and (2) changes in the performance of activities of daily living
      as measured by the Barthel index. RESULTS: After an average of 20.4+/-10.7 days
      following surgery 95 PD patients were hospitalized for an average rehabilitation
      period of 29.0+/-11.2 days. Technical dysfunctions were found in 3 (3.1%)
      patients and a bilateral electrode dislocation in 1 (1.1%) patient. Stimulation
      parameters were adjusted on 7.3+/-4.0 days, sometimes with several adjustments on
      the same day. Until discharge the stimulation amplitude was significantly
      increased from 2.1+/-0.8 V to 3.0+/-0.8 V. Moreover, in 70 (73.7%) patients
      active stimulation contacts were changed. The mean levodopa equivalent dosage
      decreased from 529+/-290 mg/die to 300+/-277 mg/die. The Barthel index increased
      significantly by 10.3+/-12.4 points. CONCLUSION: Further DBS and medication
      adjustments play an important role for hospital rehabilitation of PD patients
      after initial DBS programming in DBS centers.

PMID- 20676601
TI  - [Psychiatry as cultural science: considerations following Max Weber].
AB  - Psychiatry can be seen as a natural and cultural science. According to this the
      postulate of freedom is its strong value judgment. Since the times of
      enlightenment it has been described metaphorically by the myth of the expulsion
      from Paradise. Following Max Weber and Wilhelm Dilthey, Karl Jaspers has
      introduced this perspective into psychiatry. His strict dichotomy between
      explaining and understanding has later been critically revised by Werner Janzarik
      and Hans Heimann. Their concepts of structure dynamic, of pathography and of
      anthropology are closer to Max Weber who connected natural and cultural sciences
      in a much stronger way. Especially the pathographic example of Nietzsche allows
      to demonstrate the differences between Jaspers and the later psychopathologists
      of the Heidelberg and Tubingen schools.

PMID- 20676602
TI  - [Structures of neurooncological science and care].

PMID- 20676603
TI  - [Basic principles of MR spectroscopy].
AB  - MR spectroscopy (MRS) is a non-invasive method for investigating tissue
      metabolism. In the clinical setting proton spectroscopy based on the hydrogen
      nucleus ((1)H) is primarily used for determining concentrations of important
      brain metabolites. This paper illustrates the physicochemical principles of MRS
      and the requirements for high quality spectra. Moreover, different techniques for
      acquiring localized spectra are demonstrated.

PMID- 20676604
TI  - Copper, zinc and lead bioaccumulation in marine snail, Strombus gigas, from
      Guacanayabo Gulf, Cuba.
AB  - Levels of copper, zinc and lead were determined in sediments and edible muscle of
      marine snail Strombus gigas collected from Guacanayabo Gulf, Cuba. The
      concentration range of each metal in marine snail muscle on mg kg(-1) wet weight
      varied as follows: Cu = 6.4-32.6, Zn = 20.4-31.1 and Pb = 0.2-2.3; and in
      corresponding sediments (on mg kg(-1) dry weight) as: Cu = 157-186, Zn = 56-94
      and Pb = 20-37. The average biota-sediment accumulation factors (BSAFs) obtained
      for studied metals are less than unity in all cases, indicating that only a
      little fraction of metal content in the sediments is bioavailable, independently
      of their possible enrichments in the sediments. The concentrations of copper and
      lead in some of the marine snails are above typical public health recommended
      limits.

PMID- 20676605
TI  - Residue and bio-efficacy evaluation of controlled release formulations of
      metribuzin against weeds in wheat.
AB  - Controlled release formulations of metribuzin in polyvinyl chloride, (emulsion);
      carboxy methyl cellulose, CMC and carboxy methyl cellulose- kaolinite composite,
      CMC-KAO are reported. The MET-CMC-KAO-3 (T(9)) formulation provided a superior
      control (76.1%) of weeds in field grown wheat in comparison to metribuzin 75 DF
      (57.14%) at the dose (350 g a.i. ha(-1)) after 90 days of sowing. The treatment
      (T(9)) reduced the dry weight of the weed flora after 30 days of sowing (4.0 g m(
      2)) and significantly superior over metribuzin 75 DF (6.0 g m(-2)) and control
      (17.72 g m(-2)). There were nil to negligible metribuzin residue in soil at
      harvest of wheat crop and were within prescribed limit of 10 mg L(-1) in drinking
      water (EPA).

PMID- 20676606
TI  - Prediction of polycyclic aromatic hydrocarbons toxicity using equilibrium
      partitioning approach and narcosis model.
AB  - The study underscores the use of equilibrium partitioning (EqP) to determine
      bioavailability and the narcosis theory to estimate toxicity of PAHs to benthic
      invertebrates. Eight PAHs (anthracene, azuleno(2,1-b)thiophene,
      benz(a)anthracene, carbazole, dibenzothiophene, benz(a)azulene,
      dibenzo(a,h)anthracene and phenanthrene) were identified with phenanthrene and
      carbazole recording the highest (6.29 microg/g) and least (0.06 microg/g)
      concentrations at both seasons. Based on EqP and Narcosis model, the sum of PAHs
      toxic unit (SigmaTU), at both sites is <<1, suggesting no likelihood of PAHs
      toxicity to benthic invertebrates. The study suggests continuous PAH monitoring
      especially with aquatic species due to their transfer to human via food chain.

PMID- 20676607
TI  - Increased medial tibial slope in teenage pediatric population with open physes
      and anterior cruciate ligament injuries.
AB  - PURPOSE: Variations in bony morphology have been associated with anterior
      cruciate ligament (ACL) injury risk. The primary aim of this study was to compare
      the tibial slope in the teenage pediatric population with open physes, with and
      without ACL injury. The secondary aims were to compare the notch width index
      (NWI) and determine the influence of gender and age on tibial slope and NWI.
      METHODS: Thirty-nine teenage pediatric subjects were included in this study, 16
      with and 23 without ACL injury. Medial tibial slope and lateral tibial slope and
      NWI as measured on plain radiographs were compared between the groups using an
      independent t-test. Comparison of tibial slope and NWI was also performed between
      male and female subjects. Pearson correlation coefficient between age and tibial
      slope and NWI was calculated. RESULTS: The medial tibial slope averaged 10.2 (+/
      3.9) degrees, the lateral tibial slope 11.5 (+/-3.9) degrees, and the NWI 0.26.
      There was a significant difference in medial tibial slope between the ACL-injured
      (12.1 degrees) subjects and the controls (8.9 degrees) (P = 0.009). There was no
      significant difference in lateral tibial slope or NWI between the groups. There
      was no significant difference in the medial tibial slope and lateral tibial slope
      and NWI between the male and female subjects. Subject age was not correlated with
      medial tibial slope and lateral tibial slope or NWI. CONCLUSION: There was an
      increased medial tibial slope in ACL-injured teenagers with open physes, when
      compared to a control group of teenager with open physes without ACL injury.

PMID- 20676609
TI  - Effects of American ginseng (Panax quinquefolius) on neurocognitive function: an
      acute, randomised, double-blind, placebo-controlled, crossover study.
AB  - RATIONALE: Over the last decade, Asian ginseng (Panax ginseng) has been shown to
      improve aspects of human cognitive function. American ginseng (Panax
      quinquefolius) has a distinct ginsenoside profile from P. ginseng, promising
      cognitive enhancing properties in preclinical studies and benefits processes
      linked to human cognition. OBJECTIVES: The availability of a highly standardised
      extract of P. quinquefolius (CereboostTM) led us to evaluate its neurocognitive
      properties in humans for the first time. METHODS: This randomised, double-blind,
      placebo-controlled, crossover trial (N = 32, healthy young adults) assessed the
      acute mood, neurocognitive and glycaemic effects of three doses (100, 200 400 mg)
      of CereboostTM (P. quinquefolius standardised to 10.65% ginsenosides).
      Participants' mood, cognitive function and blood glucose were measured 1, 3 and 6
      h following administration. RESULTS: There was a significant improvement of
      working memory (WM) performance associated with P. quinquefolius. Corsi block
      performance was improved by all doses at all testing times. There were
      differential effects of all doses on other WM tasks which were maintained across
      the testing day. Choice reaction time accuracy and 'calmness' were significantly
      improved by 100 mg. There were no changes in blood glucose levels. CONCLUSIONS:
      This preliminary study has identified robust working memory enhancement following
      administration of American ginseng. These effects are distinct from those of
      Asian ginseng and suggest that psychopharmacological properties depend critically
      on ginsenoside profiles. These results have ramifications for the
      psychopharmacology of herbal extracts and merit further study using different
      dosing regimens and in populations where cognition is fragile.

PMID- 20676608
TI  - Effects of beta-adrenoceptor antagonists on alcohol drinking by alcohol-dependent
      rats.
AB  - RATIONALE: Alcohol-dependent animals display enhanced stress responsivity, reward
      thresholds, and alcohol self-administration during alcohol withdrawal, and some
      of these aspects of alcohol dependence may be mediated by activation of brain
      norepinephrine (NE) systems. OBJECTIVES: This study examined the effects of
      propranolol, a beta-adrenoceptor antagonist, on operant alcohol-reinforced
      responding by alcohol-dependent and non-dependent rats. METHODS: Adult male
      Wistar rats were trained to respond for alcohol in an operant conditioning
      paradigm on fixed-ratio-1 (FR-1) and progressive ratio (PR) reinforcement
      schedules. Rats were either made dependent on alcohol via chronic intermittent
      (14 h ON/10 h OFF) alcohol vapor inhalation or were not exposed to alcohol vapor.
      Rats were tested for the effects of propranolol (0-10 mg/kg) or nadolol (0-20
      mg/kg) on operant alcohol-reinforced responding at the time point corresponding
      to 6-8 h withdrawal in dependent animals. RESULTS: All doses of propranolol
      suppressed FR-1 operant alcohol-reinforced responding in alcohol-dependent rats,
      but only the highest dose suppressed FR-1 responding by controls. No dose of
      propranolol affected water responding. Nadolol did not affect operant behavior.
      Propranolol suppressed PR operant alcohol-reinforced responding across groups, an
      effect attributable to significant suppression of alcohol responding at the
      highest dose. CONCLUSIONS: Following development of alcohol dependence, rats
      exhibit hypersensitivity to the suppressive effects of propranolol on operant
      alcohol-reinforced responding. This effect is mediated by central actions of the
      drug, is not attributable to motor effects, and may reflect activation of brain
      NE systems that contributes to withdrawal-induced negative emotional states and
      drives alcohol drinking in the dependent organism.

PMID- 20676610
TI  - Nicotinic acetylcholine receptors are required for the conditioned reinforcing
      properties of sucrose-associated cues.
AB  - RATIONALE: We recently demonstrated that blocking specific nicotinic
      acetylcholine receptors (nAChRs) abolishes the conditioned reinforcing properties
      of ethanol-associated cues in rat, suggesting nAChRs as promising pharmacological
      targets for prevention of cue-induced relapse. OBJECTIVES: The present study
      investigated the involvement of nAChR subtypes in the conditioned reinforcing
      properties of stimuli associated with a natural reward (sucrose). METHODS: Water
      deprived rats were trained to associate a tone + light stimulus (CS) with the
      presentation of a 0.1 M sucrose solution for 10 consecutive days. On the
      subsequent day, the animals were tested on the stringent acquisition of a new
      instrumental response with conditioned reinforcement, following a systemic
      injection of the nonselective nAChR antagonist mecamylamine (MEC) or the
      selective alpha7 and alpha6/alpha3beta2beta3* nAChR antagonist methyllycaconitine
      (MLA). At testing, the rats were presented with two novel levers. Responding on
      the lever assigned as active (CR lever) resulted in a presentation of the CS
      alone, while pressing the inactive lever (NCR lever) had no programmed
      consequences. RESULTS: Control animals pressed the CR lever significantly more
      than the NCR lever, demonstrating that the CR had acquired conditioned
      reinforcing properties. Systemic MEC as well as MLA reduced the CR lever
      responses to the same level as for the NCR lever. CONCLUSIONS: These results
      demonstrate a role for the alpha7 and/or alpha6/alpha3beta2beta3* nAChRs in
      conditioned reinforcement to a natural reward and suggest neuronal nAChRs as
      common mediators of the impact of cues on incentive processes.

PMID- 20676611
TI  - Effect of tandospirone, a serotonin-1A receptor partial agonist, on information
      processing and locomotion in dizocilpine-treated rats.
AB  - RATIONALE: Augmentation therapy with serotonin-1A receptor (5-HT1A) partial
      agonists has been suggested to ameliorate psychotic symptoms in patients with
      schizophrenia. OBJECTIVE AND METHODS: The objective of the present study was to
      examine the effect of repeated administration of tandospirone (0.05 and 5 mg/kg)
      on locomotor activity in a novel environment and on sensorimotor gating in rats
      treated with the N-methyl-D-aspartate receptor antagonist MK-801, which has been
      used in animal models of schizophrenia. Furthermore, we sought to determine
      whether the effect of tandospirone on these behavioural measures is blocked by
      WAY 100635 (0.3 mg/kg), a 5-HT1A receptor antagonist, and whether there is an
      interaction between haloperidol (0.1 mg/kg; a dopamine-D2 receptor antagonist)
      and tandospirone. RESULTS: Tandospirone at 5 mg/kg, but not 0.05 mg/kg, decreased
      locomotor activity in saline or MK-801-treated rats, which were not affected by
      co-treatment with WAY 100635. Haloperidol decreased locomotion both in saline and
      MK-801-treated animals, and this effect was not evident in the latter group
      receiving the higher dose of tandospirone. Tandospirone (5 mg/kg)-induced
      disruption of sensorimotor gating in saline or MK-801-treated animals was
      reversed by WAY-100635, but not by haloperidol. CONCLUSIONS: These findings
      suggest that behavioural changes induced by tandospirone are not fully blocked by
      5-HT1A antagonists and that tandospirone (5 mg/kg) potentiates the effect of MK
      801. Overall, these findings point to an interaction between NMDA and 5-HT(1A)
      receptors. Part of the effect of tandospirone on locomotor activity may be
      mediated by the actions of its active metabolites on other neurotransmitter
      systems.

PMID- 20676612
TI  - A within-subject cognitive battery in the rat: differential effects of NMDA
      receptor antagonists.
AB  - RATIONALE: The range of cognitive and psychotomimetic effects produced by
      antagonists of the N-methyl-D-aspartate (NMDA) receptor has lead to widespread
      usage of these molecules as pharmacological models of cognitive impairment for
      drug discovery. Historically, NMDA receptor antagonists have been used
      interchangeably on the assumption that they produce analogous effects.
      OBJECTIVES: To profile a subset of these antagonists across a novel within
      subject cognitive battery in the rat. METHODS: Naive male Lister Hooded rats were
      subjected to a series of tests in which they were required to learn a simple
      visuo-auditory conditional discrimination. They then underwent testing in a
      delayed discrimination test followed by rule reversal and rule extinction tests.
      RESULTS: All NMDA receptor antagonists tested impaired acquisition performance
      and, with the exception of ketamine and the GluN2A preferring antagonist, NVP
      AAM077, impaired consolidation of extinction. GluN2B antagonism produced a
      singular profile with potentially enhanced delayed discrimination performance and
      reduced hit rates in the reversal phase. Only PCP (phencyclidine) and ketamine
      disrupted performance in the delay phase but did so in a delay-independent
      manner. MK-801, PCP and memantine all increased the hit rate in the reversal
      phase; whilst only MK-801 and PCP impaired extinction per se. CONCLUSIONS: NMDA
      receptor-dependent mechanisms are requisite in the acquisition of a simple
      conditional discrimination and consolidation of extinction. Their role in working
      memory and reversal tasks appear to be less critical and potentially specific to
      the paradigm and NMDA receptor antagonist used. It is clearly misleading to
      generalise across NMDA antagonists with respect to their preclinical cognitive
      profile.

PMID- 20676613
TI  - Validation and pharmacological characterisation of MK-801-induced locomotor
      hyperactivity in BALB/C mice as an assay for detection of novel antipsychotics.
AB  - RATIONALE: We evaluated locomotor hyperactivity induced in BALB/C mice by an N
      methyl-D-aspartate receptor antagonist MK-801 as an assay for the detection of
      antipsychotic drugs. OBJECTIVES: We assessed the effects of antipsychotic drugs
      to validate the assay (study 1), selective dopamine and serotonin ligands for
      pharmacological characterisation of the model (study 2) and a number of compounds
      with efficacy in models of schizophrenia to understand the predictive validity of
      the model (study 3). METHODS: Adult males (n  = 9/group) were pretreated with a
      test compound, habituated to locomotor activity cages before receiving MK-801
      (0.32 mg/kg) and activity recorded for a further 75 or 120 min. In study 1, we
      tested haloperidol, clozapine, olanzapine, risperidone, ziprasidone,
      aripiprazole, sertindole and quetiapine. In study 2, we tested SCH23390 (D(1)
      antagonist), sulpiride (D(2)/D(3) antagonist), raclopride (D(2)/D(3) antagonist),
      SB-277011 (D(3) antagonist), L-745,870 (D(4) antagonist), WAY100635 (5-HT(1A)
      antagonist), 8-OH-DPAT (5-HT(1A) agonist), ketanserin (5-HT(2A)/5-HT(2C)
      antagonist) and SB-242084 (5-HT(2C) antagonist). In study 3, we tested xanomeline
      (M(1)/M(4) receptor agonist), LY379268 (mGluR2/3 receptor agonist), diazepam
      (GABA(A) modulator) and thioperamide (H(3) receptor antagonist). RESULTS: All
      antipsychotics suppressed MK-801-induced hyperactivity in a dose-dependent and
      specific manner. The effects of antipsychotics appear to be mediated via dopamine
      D(1), D(2) and 5-HT(2) receptors. Xanomeline, LY379268 and diazepam were active
      in this assay while thioperamide was not. CONCLUSIONS: MK-801-induced
      hyperactivity in BALB/C mice model of positive symptoms has shown predictive
      validity with novel compounds acing at M(1)/M(4), mGluR2/3 and GABA(A) receptors
      and can be used as a screening assay for detection of novel pharmacotherapies
      targeting those receptors.

PMID- 20676615
TI  - Nanosensing of Fcgamma receptors on macrophages.
AB  - Determining the distribution of specific binding sites on biological samples with
      high spatial accuracy (in the order of several nanometer) is an important
      challenge in many fields of biological science. Combination of high-resolution
      atomic force microscope (AFM) topography imaging with single-molecule force
      spectroscopy provides a unique possibility for the detection of specific
      molecular recognition events. The identification and localization of specific
      receptor binding sites on complex heterogeneous biosurfaces such as cells and
      membranes are of particular interest in this context. Simultaneous topography and
      recognition imaging was used to unravel the nanolandscape of cells of the immune
      system such as macrophages. The most studied phagocytic receptors include the Fc
      receptors that bind to the Fc portion of immunoglobulins. Here, nanomapping of
      FcgammaRs (Fc receptors for immunoglobulin G (IgG)) was performed on fixed
      J774.A1 mouse macrophage cell surfaces with magnetically coated AFM tips
      functionalized with Fc fragments of mouse IgG via long and flexible poly(ethylene
      glycol) linkers. Because of possible AFM tip engulfment on living macrophages,
      appropriate cell fixation procedure leaving the binding activity of FcgammaRs
      practically intact was elaborated. The recognition maps revealed prominent spots
      (microdomains) more or less homogeneously distributed on the macrophage surface
      with the sizes from 4 to 300 nm. Typical recognition image contained about ~4% of
      large clusters (>200 nm), which were surrounded by a massive number (~50%) of
      small-size (4-30 nm) and the rest by middle-size (50, 150 nm) domains. These
      spots were detected from the decrease of oscillation amplitude during specific
      binding between Fc-coated tip and FcgammaRs on macrophage surfaces. In addition,
      the effect of osmotic swelling on the topographical landscape of macrophage
      surfaces and on the reorganization of FcgammaRs was investigated.

PMID- 20676616
TI  - Electrochemical impedance spectroscopy in label-free biosensor applications:
      multivariate data analysis for an objective interpretation.
AB  - Electrochemical impedance spectroscopy plays an important role in biosensor
      science thanks to the possibility of finding specific information from processes
      with different kinetics at a chosen electrode potential in one experiment. In
      this paper we briefly discuss label-free impedimetric biosensors described in the
      literature. A novel method for neutral interpretation of impedance data is
      presented that includes complex number chemometrics. Three examples are given
      based on impedance measurements on synthetic biomembranes, in this case a lipid
      monolayer deposited on a mercury electrode. The interaction of various compounds
      with the monomolecular lipid layer is illustrated with the following: (1)
      different concentrations of magainin (Geladi et al. in Proc. Int. Fed. Med.
      Biomed. Eng. 9:219-220, 2005); (2) different derivatives of gramicidin A
      (Lindholm-Sethson et al. in Langmuir 24:5029-5032, 2007), and (3) an
      antimicrobial peptide (Ringstad et al. in Langmuir 24:208-216, 2008).

PMID- 20676614
TI  - The effects of acute treatment with escitalopram on the different stages of
      contextual fear conditioning are reversed by atomoxetine.
AB  - RATIONALE: Although the antidepressant and anxiolytic effects of selective
      serotonin reuptake inhibitors and serotonin-noradrenaline reuptake inhibitors are
      well-documented, less is known about their cognitive effects. OBJECTIVE:
      Escitalopram, a selective serotonin reuptake inhibitor, and atomoxetine, a
      selective noradrenaline reuptake inhibitor, were used to evaluate the interaction
      between noradrenergic and serotonergic neurotransmission in the modulation of
      contextual fear conditioning in rats. METHODS: Contextual fear-conditioning test
      was used to investigate the acute effects of escitalopram, alone or in
      combination with atomoxetine, in different stages of learning and memory in rats.
      Furthermore, microdialysis in freely moving animals was used to investigate the
      effect of escitalopram on serotonin, dopamine, and noradrenaline levels in the
      rat hippocampus. RESULTS: Escitalopram significantly increased conditioned
      responses when applied before the acquisition, but decreased responses, when
      applied before the recall test. When administered during memory consolidation,
      escitalopram dose-dependently enhanced conditioned responding. These effects were
      blocked by atomoxetine. Escitalopram (at a dose that affects memory
      consolidation) increased hippocampal serotonin levels fourfold without changing
      dopamine or noradrenaline. Atomoxetine, at dose levels that blocked the effects
      of escitalopram on contextual fear conditioning, increased the extracellular
      levels of noradrenaline eightfold but did not change dopamine or serotonin. A
      combined treatment of escitalopram and atomoxetine caused a significant
      attenuation of escitalopram-induced increase in serotonin levels, while
      noradrenaline levels were not affected. CONCLUSIONS: These findings indicate that
      escitalopram affects fear memory in rats, likely modulated by increases in
      serotonin levels in the brain. This effect is impaired by atomoxetine, probably
      due to a noradrenaline-mediated decrease in serotonin levels. Further studies are
      warranted to study the effects of potential differences among antidepressant
      therapies on long-term cognitive outcomes.

PMID- 20676617
TI  - Screening of perfluorinated chemicals (PFCs) in various aquatic organisms.
AB  - The aim of this study was to evaluate the occurrence of five perfluorinated
      chemicals (perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA),
      perfluorononanoic acid (PFNA), perfluorohexane sulfonic acid (PFHxS), and
      perfluorobutane sulfonic acid) in aquatic organisms dwelling in either freshwater
      or marine ecosystems. Organisms selected were insect larvae, oysters, zebra
      mussels, sardines, and crabs, which are widespread in the environment and may
      represent potential bioindicators of exposure to PFCs. The study comprises the
      optimization of a solid-liquid extraction method and determination by high
      performance liquid chromatography coupled to tandem mass spectrometry. Using
      spiked zebra mussels at 10 and 100 ng/g level, the method developed provided
      recoveries of 96% and 122%, and 82% to 116%, respectively, and a limit of
      detection between 0.07 and 0.22 ng/g ww. The method was highly sensitivity and
      robust to determine PFC compounds in a wide array of biological matrices, and no
      matrix interferents nor blank contamination was observed. Among organisms
      studied, none of the bivalves accumulated PFCs, and contrarily, insect larvae,
      followed by fish and crabs contained levels ranging from 0.23 to 144 ng/g ww of
      PFOS, from 0.14 to 4.3 ng/g ww of PFOA, and traces of PFNA and PFHxS. Assessment
      of the potential use of aquatic organisms for biomonitoring studies is further
      discussed.

PMID- 20676618
TI  - Plasmonics nanoprobes: detection of single-nucleotide polymorphisms in the breast
      cancer BRCA1 gene.
AB  - This paper describes the application of plasmonics-based nanoprobes that combine
      the modulation of the plasmonics effect to change the surface-enhanced Raman
      scattering (SERS) of a Raman label and the specificity of a DNA hairpin loop
      sequence to recognize and discriminate a variety of molecular target sequences.
      Hybridization with target DNA opens the hairpin and physically separates the
      Raman label from the metal nanoparticle thus reducing the plasmonics effect and
      quenching the SERS signal of the label. We have successfully demonstrated the
      specificity and selectivity of the nanoprobes in the detection of a single
      nucleotide polymorphism (SNP) in the breast cancer BRCA1 gene in a homogenous
      solution at room temperature. In addition, the potential application of
      plasmonics nanoprobes for quantitative DNA diagnostic testing is discussed.

PMID- 20676620
TI  - The potential of microelectrode arrays and microelectronics for biomedical
      research and diagnostics.
AB  - Planar microelectrode arrays (MEAs) are devices that can be used in biomedical
      and basic in vitro research to provide extracellular electrophysiological
      information about biological systems at high spatial and temporal resolution.
      Complementary metal oxide semiconductor (CMOS) is a technology with which MEAs
      can be produced on a microscale featuring high spatial resolution and excellent
      signal-to-noise characteristics. CMOS MEAs are specialized for the analysis of
      complete electrogenic cellular networks at the cellular or subcellular level in
      dissociated cultures, organotypic cultures, and acute tissue slices; they can
      also function as biosensors to detect biochemical events. Models of disease or
      the response of cellular networks to pharmacological compounds can be studied in
      vitro, allowing one to investigate pathologies, such as cardiac arrhythmias,
      memory impairment due to Alzheimer's disease, or vision impairment caused by
      ganglion cell degeneration in the retina.

PMID- 20676621
TI  - Torsades de pointes tachycardia induced by common cold compound medication
      containing chlorpheniramine.

PMID- 20676622
TI  - Whole-body diffusion-weighted imaging for staging malignant lymphoma in children.
AB  - CT is currently the mainstay in staging malignant lymphoma in children, but the
      risk of second neoplasms due to ionizing radiation associated with CT is not
      negligible. Whole-body MRI techniques and whole-body diffusion-weighted imaging
      (DWI) in particular, may be a good radiation-free alternative to CT. DWI is
      characterized by high sensitivity for the detection of lesions and allows
      quantitative assessment of diffusion that may aid in the evaluation of malignant
      lymphomas. This article will review whole-body MRI techniques for staging
      malignant lymphoma with emphasis on whole-body DWI. Furthermore, future
      considerations and challenges in whole-body DWI will be discussed.

PMID- 20676623
TI  - Persistent hypoglossal artery.

PMID- 20676624
TI  - Cerebral biometry at birth and at 4 and 8 months of age. A prospective study
      using US.
AB  - BACKGROUND: Although longitudinal reference intervals for ventricular size are
      crucial for the diagnosis of dilated ventricles, such data are sparse. OBJECTIVE:
      To establish references for ventricular measurements at birth, and at 4 and 8
      months follow-up, and to examine the inter-observer variation of the
      measurements. MATERIALS AND METHODS: This prospective, longitudinal study
      included 120 term newborns (boys 65, girls 55), mean age 1.5 days on initial
      scans, with re-examination at 4 months and 8 months of age. One examiner
      performed all the examinations, measuring: ventricular index, frontal horn width,
      third ventricle width, frontal subarachnoid space depth, optic nerve sheath
      diameter and resistive index. RESULTS: One hundred eight (90%) and 90 (75%) of
      the infants, respectively, attended for follow-up at 4 and 8 months of age. All
      measures increased with age, except for the depth of the subarachnoid spaces that
      showed an initial rise, followed by a mild drop at 8 months, and for the
      resistive index that remained stable at 0.6. The increase was particularly
      significant for frontal horn width with an increase from 2.2 mm at birth to 6.5
      mm at 4 months in boys, and 2.1-5.8 mm in girls. The agreement between two
      observers was fair to moderate for most of the measurements. CONCLUSION: The
      increase in the width of the frontal horns between birth and 4 months of age, as
      well as the wide normal range found among all three age groups are noteworthy and
      should inform future diagnostics.

PMID- 20676625
TI  - Bacterial activity and bacterioplankton diversity in the eutrophic River Warnow-
      direct measurement of bacterial growth efficiency and its effect on carbon
      utilization.
AB  - The influence of bacterial activity and diversity on bacterial growth efficiency
      was investigated in a flatland river. Eutrophic River Warnow drains predominantly
      agricultural land and is heavily loaded with nutrients, dissolved and particulate
      organic matter (DOM and POM), especially humic substances. Although the water
      column bacterial community consists of many inactive or damaged cells,
      bacterioplankton sustained a high bacterial secondary production of 0.2-14.5 MUg
      C L(-1) h(-1) and a high DNA synthesis (thymidine uptake) of 6.1-15.5 MUg C L(-1)
      h(-1). The direct and short-term measurement of bacterial respiration (by
      optodes) revealed high respiration rates especially in summer leading to directly
      estimated bacterial growth efficiencies (BGE) of 2-28%. These values are compared
      to calculations based only on bacterial production, which considerably
      overestimated BGEs. From all these data, River Warnow can be characterized as a
      strongly remineralizing system. River Warnow was dominated among others by
      Cytophaga/Flavobacteria and Actinobacteria which are typical for organic rich
      waters because of their ability to degrade high molecular weight compounds.
      However, community composition did not significantly affect BGE.

PMID- 20676626
TI  - Structure and dynamics of the microbial communities underlying the carboxylate
      platform for biofuel production.
AB  - The carboxylate platform utilizes a mixed microbial community to convert
      lignocellulosic biomass into chemicals and fuels. While much of the platform is
      well understood, little is known about its microbiology. Mesophilic (40 degrees
      C) and thermophilic (55 degrees C) fermentations employing a sorghum feedstock
      and marine sediment inoculum were profiled using 16S rRNA tag-pyrosequencing over
      the course of a 30-day incubation. The contrasting fermentation temperatures
      converted similar amounts of biomass, but the mesophilic community was
      significantly more productive, and the two temperatures differed significantly
      with respect to propionic and butyric acid production. Pyrotag sequencing
      revealed the presence of dynamic communities that responded rapidly to
      temperature and changed substantially over time. Both temperatures were dominated
      by bacteria resembling Clostridia, but they shared few taxa in common. The
      species-rich mesophilic community harbored a variety of Bacteroidetes,
      Actinobacteria, and gamma-Proteobacteria, whereas the thermophilic community was
      composed mainly of Clostridia and Bacilli. Despite differences in composition and
      productivity, similar patterns of functional class dynamics were observed. Over
      time, organisms resembling known cellulose degraders decreased in abundance,
      while organisms resembling known xylose degraders increased. Improved
      understanding of the carboxylate platform's microbiology will help refine
      platform performance and contribute to our growing knowledge regarding biomass
      conversion and biofuel production processes.

PMID- 20676627
TI  - Functional and structural characterization of soluble recombinant epsilon toxin
      of Clostridium perfringens D, causative agent of enterotoxaemia.
AB  - Clostridium perfringens types B and D are responsible for enterotoxaemia, one of
      the major causes of cattle mortality and is therefore of great economic concern.
      The epsilon toxin produced by the organism is the major antigenic determinant and
      has been directly implicated for the disease causation. In the present paper, we
      evaluated the biological activity of the recombinant epsilon toxin (rEtx)
      produced as soluble protein in Escherichia coli. The rEtx was purified to near
      homogeneity by a one-step anion-exchange chromatography. The immunological
      identity of purified rEtx was confirmed by Western blotting using a monoclonal
      antibody against the native toxin. The rEtx formed heptamer in the Madin-Darby
      canine kidney (MDCK) cells and synaptosomal membrane of mouse brain and was
      cytotoxic to the MDCK cells with a CT(50) of 30 ng/ml. The rEtx was highly stable
      and its thermostability profile related well with its biological activity. The
      rEtx was purified in large amounts and exhibited all the properties of native
      toxin and therefore can be used for the development of vaccine against the
      pathogen.

PMID- 20676629
TI  - Yeast flocculation and its biotechnological relevance.
AB  - Adhesion properties of microorganisms are crucial for many essential biological
      processes such as sexual reproduction, tissue or substrate invasion, biofilm
      formation and others. Most, if not all microbial adhesion phenotypes are
      controlled by factors such as nutrient availability or the presence of
      pheromones. One particular form of controlled cellular adhesion that occurs in
      liquid environments is a process of asexual aggregation of cells which is also
      referred to as flocculation. This process has been the subject of significant
      scientific and biotechnological interest because of its relevance for many
      industrial fermentation processes. Specifically adjusted flocculation properties
      of industrial microorganisms could indeed lead to significant improvements in the
      processing of biotechnological fermentation products such as foods, biofuels and
      industrially produced peptides. This review briefly summarises our current
      scientific knowledge on the regulation of flocculation-related phenotypes, their
      importance for different biotechnological industries, and possible future
      applications for microorganisms with improved flocculation properties.

PMID- 20676628
TI  - Direct ethanol production from cellulosic materials at high temperature using the
      thermotolerant yeast Kluyveromyces marxianus displaying cellulolytic enzymes.
AB  - To exploit cellulosic materials for fuel ethanol production, a microorganism
      capable of high temperature and simultaneous saccharification-fermentation has
      been required. However, a major drawback is the optimum temperature for the
      saccharification and fermentation. Most ethanol-fermenting microbes have an
      optimum temperature for ethanol fermentation ranging between 28 degrees C and 37
      degrees C, while the activity of cellulolytic enzymes is highest at around 50
      degrees C and significantly decreases with a decrease in temperature. Therefore,
      in the present study, a thermotolerant yeast, Kluyveromyces marxianus, which has
      high growth and fermentation at elevated temperatures, was used as a producer of
      ethanol from cellulose. The strain was genetically engineered to display
      Trichoderma reesei endoglucanase and Aspergillus aculeatus beta-glucosidase on
      the cell surface, which successfully converts a cellulosic beta-glucan to ethanol
      directly at 48 degrees C with a yield of 4.24 g/l from 10 g/l within 12 h. The
      yield (in grams of ethanol produced per gram of beta-glucan consumed) was 0.47
      g/g, which corresponds to 92.2% of the theoretical yield. This indicates that
      high-temperature cellulose fermentation to ethanol can be efficiently
      accomplished using a recombinant K. marxianus strain displaying thermostable
      cellulolytic enzymes on the cell surface.

PMID- 20676630
TI  - Surface display of active lipases Lip7 and Lip8 from Yarrowia lipolytica on
      Saccharomyces cerevisiae.
AB  - Lipase has been used widely in industry. In this study, we have constructed two
      recombinant Saccharomyces cerevisiae strains displaying two active lipases on the
      cell surface by cell surface engineering. The genes encoding Yarrowia lipolytica
      lipases Lip7 and Lip8 were fused with the gene encoding small binding subunit
      Aga2 of a-agglutinin. Localization of the Lip7 and Lip8 on the cell surface was
      confirmed by immunofluorescence microscopy. Besides, the putative signal
      sequences of Lip7 and Lip8 were removed to compare their effect on the activities
      of surface-displayed lipases. The results showed that the activities towards p
      nitrophenyl caprylate of surface-displayed Lip7 and Lip8 were 283 U/g (dry cell)
      and 121 U/g (dry cell), much higher than that using Flo1 as anchor protein in
      Pichia pastoris, and the putative signal sequences have significant effect on the
      activities of the displayed lipases; when deleted, the lipases' activities were
      declined to 65 U/g (dry cell) and 80 U/g (dry cell), respectively. The displayed
      lipases exhibit a preference for middle chain fatty acids and a high thermal
      stability. Additionally, from the study, to surface-display a target protein, it
      is recommendable that the structure feature of the protein should be assayed
      through bioinformatics methods and then the cell wall proteins with the anchor
      domain far away from the activity center should be chosen as anchor proteins.

PMID- 20676631
TI  - Characterization of enzymes involved in the central metabolism of Gluconobacter
      oxydans.
AB  - Gluconobacter oxydans is an industrially important bacterium that lacks a
      complete Embden-Meyerhof pathway (glycolysis). The organism instead uses the
      pentose phosphate pathway to oxidize sugars and their phosphorylated
      intermediates. However, the lack of glycolysis limits the amount of NADH as
      electron donor for electron transport phosphorylation. It has been suggested that
      the pentose phosphate pathway contributes to NADH production. Six enzymes
      predicted to play central roles in intracellular glucose and gluconate flux were
      heterologously overproduced in Escherichia coli and characterized to investigate
      the intracellular flow of glucose and gluconates into the pentose phosphate
      pathway and to explore the contribution of the pentose phosphate pathway to NADH
      generation. The key pentose phosphate enzymes glucose 6-phosphate dehydrogenase
      (Gox0145) and 6-phosphogluconate dehydrogenase (Gox1705) had dual cofactor
      specificities but were physiologically NADP- and NAD-dependent, respectively.
      Putative glucose dehydrogenase (Gox2015) was NADP-dependent and exhibited a
      preference for mannose over glucose, whereas a 2-ketogluconate reductase
      (Gox0417) displayed dual cofactor specificity for NAD(P)H. Furthermore, a
      putative gluconokinase and a putative glucokinase were identified. The
      gluconokinase displayed high activities with gluconate and is thought to shuttle
      intracellular gluconate into the pentose phosphate pathway. A model for the
      trafficking of glucose and gluconates into the pentose phosphate pathway and its
      role in NADH generation is presented. The role of NADPH in chemiosmotic energy
      conservation is also discussed.

PMID- 20676632
TI  - Bioremediation of glyphosate-contaminated soils.
AB  - Based on the results of laboratory and field experiments, we performed a
      comprehensive assessment of the bioremediation efficiency of glyphosate
      contaminated soddy-podzol soil. The selected bacterial strains Achromobacter sp.
      Kg 16 (VKM B-2534D) and Ochrobactrum anthropi GPK 3 (VKM B-2554D) were used for
      the aerobic degradation of glyphosate. They demonstrated high viability in soil
      with the tenfold higher content of glyphosate than the recommended dose for the
      single in situ treatment of weeds. The strains provided a two- to threefold
      higher rate of glyphosate degradation as compared to indigenous soil microbial
      community. Within 1-2 weeks after the strain introduction, the glyphosate content
      of the treated soil decreased and integral toxicity and phytotoxicity diminished
      to values of non-contaminated soil. The decrease in the glyphosate content
      restored soil biological activity, as is evident from a more than twofold
      increase in the dehydrogenase activity of indigenous soil microorganisms and
      their biomass (1.2-fold and 1.6-fold for saprotrophic bacteria and fungi,
      respectively). The glyphosate-degrading strains used in this study are not
      pathogenic for mammals and do not exhibit integral toxicity and phytotoxicity.
      Therefore, these strains are suitable for the efficient, ecologically safe, and
      rapid bioremediation of glyphosate-contaminated soils.

PMID- 20676633
TI  - Metabolic selective pressure stabilizes plasmids carrying biosynthetic genes for
      reduced biochemicals in Escherichia coli redox mutants.
AB  - Several biotechnological processes rely on the utilization of high-copy-number
      plasmids for heterologous gene expression, and understanding the interactions
      between plasmid DNA and bacterial hosts is highly relevant for bioprocess
      optimization. We assessed metabolic modifications and physiological changes
      exerted by expression of a plasmid-encoded alcohol-acetaldehyde dehydrogenase
      from Leuconostoc mesenteroides (adhE ( Lm )) in Escherichia coli redox mutants.
      Plasmid pET( Lm ), a pBluescript II KS(-)-derivative carrying adhE ( Lm ), was
      introduced in E. coli CT1061 [arcA creC(Con)]. This recombinant was able to
      attain a higher ethanol concentration in glycerol cultures compared to the
      parental strain. pBluescript II KS(-) was rapidly lost in 72-h bioreactor
      cultures (7.8 +/- 1.2% of plasmid-bearing cells), while pET( Lm ) was present in
      92.4 +/- 7.2% of the cells. In E. coli CT1061 carrying pBluescript II KS(-) the
      plasmid copy number steadily diminished in bioreactor cultures to reach 334 +/-
      45 copies per chromosome at 72 h, while pET( Lm ) was stably maintained, reaching
      498 +/- 18 copies per chromosome at the end of the cultivation. Plasmid pETOmega(
      Lm ), bearing a defective copy of adhE ( Lm ) interrupted by cat, reached 293 +/-
      62 copies per chromosome, implying a functional role of adhE ( Lm ) on plasmid
      maintenance. The intracellular NADH/NAD(+) content suggest that regeneration of
      oxidized co-factors by the heterologous bioreaction might play a relevant role in
      plasmid maintenance.

PMID- 20676634
TI  - Advanced tool for characterization of microbial cultures by combining cytomics
      and proteomics.
AB  - Flow cytometry approaches are applicable to recover sub-populations of microbial
      cultures in a purified form. To examine the characteristics of each sorted cell
      population, Omics technologies can be used for comprehensively monitoring
      cellular physiology, adaptation reactions, and regulated processes. In this
      study, we combined flow cytometry and gel-free proteomic analysis to investigate
      an artificial mixed bacterial culture consisting of Escherichia coli K-12 and
      Pseudomonas putida KT2440. Therefore, a filter-based device technique and an on
      membrane digestion protocol were combined in conjunction with liquid
      chromatography and mass spectrometry. This combination enabled us to identify 903
      proteins from sorted E. coli K-12 and 867 proteins from sorted P. putida KT2440
      bacteria from only 5 x 10(6) cells of each. Comparative proteomic analysis of
      sorted and non-sorted samples was done to prove that sorting did not
      significantly influence the bacterial proteome profile. We further investigated
      the physicochemical properties, namely M (r), pI, hydropathicity, and
      transmembrane helices of the proteins covered. The on-membrane digestion protocol
      applied did not require conventional detergents or urea, but exhibited similar
      recovery of all protein classes as established protocols with non-sorted
      bacterial samples.

PMID- 20676635
TI  - The cartilage black line sign: an unexpected MRI appearance of deep cartilage
      fissuring in three patients.
AB  - Many patterns of cartilage signal anomalies have been described in the knee since
      the advent of magnetic resonance imaging (MRI). With the now widespread use of
      preoperative MRI, some of these anomalies have proven to represent true
      pathology, while others have been shown to be normal variants or artifacts at
      arthroscopy. We describe three patients with an MR cartilage abnormality, not
      previously illustrated in the literature, consisting of a thin dark signal line
      on T2-weighted imaging, oriented perpendicular to the plane of imaging. This
      aberration proved to represent a deep cartilage cleft at arthroscopy (two
      patients) and at CT arthrography (one patient). Such full thickness fissures are
      generally considered to have the opposite appearance, that of fluid signal
      intensity on T2-weighted images.

PMID- 20676636
TI  - Ultrasound features of tophi in chronic tophaceous gout.
AB  - OBJECTIVE: To describe the different and lesser-known ultrasound features of
      tophi in chronic tophaceous gout. METHODS: Ultrasound images of 138 affected
      areas were analyzed from 31 patients with gout, using high-quality broadband
      linear transducers (frequency range of 8-14 MHz). Tophi were classified relative
      to echogenicity, echotexture, contours, number and the presence or absence of
      hypoechoic halo. The duration of illness was correlated with the presence of
      calcifications in tophi. RESULTS: Hyperechoic tophi were seen in 133 areas
      (96.3%); these were most frequently hyperechoic and heterogeneous (37.6%) or
      hyperechoic and heterogeneous with calcification (32.6%). Contours were found to
      be poorly defined in 115 (83.3%) areas. Multiple grouped tophi were seen in 85
      areas (61.6%) and 50 areas (36.2%) had individual tophi. In 77 examined areas
      (55.8%), there was a hypoechoic halo around the tophi. There was no correlation
      between illness duration and presence of calcifications on tophi. CONCLUSIONS:
      Tophi are generally hyperechoic, heterogeneous, with poorly defined contours,
      multiple grouped and surrounded by an anechoic halo. Individual tophus and the
      absence of association between illness duration and the presence of calcification
      are newly described features. This study of tophaceous gout by ultrasound may
      contribute to the diagnostic elucidation of patients with clinically atypical
      gout and show its diverse characteristic forms of presentation.

PMID- 20676637
TI  - Sonography and MRI of latissimus dorsi strain injury in four elite athletes.
AB  - OBJECTIVE: The objective of this study was to describe the MR and sonographic
      findings in latissimus dorsi (LD) muscle strain in athletes, and to review the
      most common injuries described in the literature, most of which are humeral
      avulsions. MATERIAL AND METHODS: Four injuries and two reinjuries of the
      myotendinous junction of the LD were followed from the day of injury until the
      return to play. Sonography (US) and MR imaging were performed in each case to
      confirm the diagnosis and to monitor the healing process. RESULTS: All cases had
      acute and isolated pain in the back of the shoulder while performing an eccentric
      maneuver of the arm and the shoulder. US and MR images demonstrated that injuries
      were located in the middle and cranial portion of the latissimus dorsi
      surrounding the myotendinous junction. After rehabilitation, all players played
      at high level again. CONCLUSIONS: Isolated lesions of LD are very rare. They can
      be demonstrated by US and MR images.

PMID- 20676638
TI  - Prospective study of p-[123I]iodo-L-phenylalanine and SPECT for the evaluation of
      newly diagnosed cerebral lesions: specific confirmation of glioma.
AB  - PURPOSE: The differentiation between gliomas, metastases and gliotic or
      inflammatory lesions by imaging techniques remains a challenge. Gliomas
      frequently exhibit increased uptake of radiolabelled amino acids and are thus
      amenable to PET or SPECT imaging. Recently, p-[123I]iodo-L-phenylalanine (IPA)
      was validated for the visualization of glioma by SPECT and received orphan drug
      status. Here we investigated its diagnostic performance for differentiating
      indeterminate brain lesions. METHODS: This prospective open study included 67
      patients with newly diagnosed brain lesions suspicious for glioma (34 without and
      33 with contrast enhancement in the MRI scan). Patients received 250 MBq IPA
      intravenously after overnight fasting. SPECT images at 30 min and 3 h post
      injection were iteratively reconstructed and visually interpreted after image
      fusion with an MRI brain scan (fluid-attenuated inversion recovery sequence or T1
      weighted contrast-enhanced image). Findings were correlated with results of
      stereotactic or open biopsies or serial imaging. RESULTS: Twenty-seven low-grade
      (2 WHO I, 25 WHO II) and 24 high-grade gliomas (1 WHO III, 23 WHO IV), 3
      metastases originating from lung cancer as well as 13 non-neoplastic lesions were
      proven. All non-neoplastic lesions and all metastases were negative with IPA
      SPECT. Forty gliomas were true-positive (TP) and 11 false-negative (FN) findings
      (8 WHO II, 1 WHO III, 2 WHO IV) occurred. There were no false-positive (FP)
      findings. For the differentiation of primary brain tumours and non-neoplastic
      lesions, sensitivity and specificity were 78 and 100%. In 34 lesions without
      contrast enhancement in MRI, IPA SPECT resulted in 17 TP, 8 true-negative, 9 FN
      and no FP findings (sensitivity 65%, specificity 100%). CONCLUSION: In patients
      with suspected glioma, IPA SPECT shows a high specificity, but especially in low
      grade gliomas FN findings may occur. Due to the high positive predictive value a
      positive finding allows a suspected glioma to be confirmed.

PMID- 20676639
TI  - Standards of practice: quality assurance guidelines for percutaneous treatments
      of intervertebral discs.
AB  - Percutaneous treatments are used in the therapy of small- to medium-sized hernias
      of intervertebral discs to reduce the intradiscal pressure in the nucleus and
      theoretically create space for the herniated fragment to implode inward, thus
      reducing pain and improving mobility and quality of life. These techniques
      involve the percutaneous removal of the nucleus pulposus by using a variety of
      chemical, thermal, or mechanical techniques and consist of removal of all or part
      of nucleus pulposus to induce more rapid healing of the abnormal lumbar disc.
      These guidelines are written to be used in quality improvement programs for
      assessing fluoroscopy- and/or computed tomography-guided percutaneous
      intervertebral disc ablative techniques.

PMID- 20676640
TI  - Prognostic impact of bleomycin-induced pneumonitis on the outcome of Hodgkin's
      lymphoma.
AB  - Bleomycin-induced pneumonitis (BIP) has been well described in Hodgkin's lymphoma
      (HL) patients. The impact of BIP on patients uniformly treated with adriamycin,
      bleomycin, vinblastine, and dacarbazine (ABVD) is not clear; previous studies
      have included patients treated with both ABVD and hybrid regimens. We reviewed
      our experience with BIP in HL to better understand the impact of BIP on overall
      survival. One hundred and eighty four consecutive patients who were treated with
      ABVD for newly diagnosed HL were eligible for retrospective review. BIP was
      defined by the presence of pulmonary symptoms, bilateral interstitial infiltrates
      on chest X-ray, computed tomography or presence of lung fibrosis on
      transbronchial lung biopsy, and the absence of infection. Patients were required
      to meet all three criteria to be included in the BIP group. BIP was observed in
      28 patients (15%). A low albumin level and the use of colony granulocyte
      stimulating factor were associated with a higher risk of developing BIP. Age,
      smoking history, and underlying lung function were not predictive of BIP.
      Importantly, patients with BIP had similar rates of 5-year overall survival
      compared to unaffected patients. There were no deaths from BIP. Omission of
      bleomycin from subsequent treatment did not adversely affect the outcomes.

PMID- 20676642
TI  - Overlapping juvenile idiopathic arthritis and systemic lupus erythematosus: a
      case report.
AB  - Hereby, we report the case of a 12-year-old girl developing oligoarthritis and
      progressing into a polyarticular form. Rheumatoid factor was positive, and
      juvenile idiopathic arthritis (JIA) was diagnosed. After a poor response to
      DMARDs, an anti-TNF agent (infliximab) was initiated, but to be discontinued due
      to an allergic reaction. The same complication was observed with the fully human
      derivative, adalimumab. At the age of 22, the patient presented septicemia with
      severe anemia and subsequent development of leukopenia, myocarditis with heart
      failure, and ANA, aSm, aSS-A, aCL positives, and nephrotic syndrome. These new
      clinical manifestations fulfilled the classification criteria for the diagnosis
      of systemic lupus erythematosus. Due to the poor therapeutic responses for both
      diseases, alternative medical options have to be considered, such as targeted
      therapy with anti-CD20 or interleukin-6 receptor antagonist monoclonal
      antibodies. This patient may also be a candidate for autologous hemopoietic stem
      cell transplantation.

PMID- 20676644
TI  - The relationship between tender point count and disease severity in patients with
      primary fibromyalgia.
AB  - Objective of this study is to asses the relationship between tender point count
      (TPC) and the severity of disease in patients with primary fibromyalgia (FM). One
      hundred and seven female patients with FM diagnosis according to ACR criteria
      were included to the study. Main outcome measures were fibromyalgia impact
      questionnaire (FIQ), Beck depression inventory (BDI), visual analog scale (VAS)
      and tender point assessment. Mean TPC was 14.66 +/- 2.50 and mean VAS was 6.6 +/-
      1.2 cm. Mean total FIQ score and BDI was 62.75 +/- 15.57 and 16.17 +/- 7.12,
      respectively. TPC was correlated positively with FIQ and VAS scores. There was no
      correlation between TPC and age and duration of symptoms. In conclusion, TPC is a
      simple and noninvasive examination finding that can supply information about the
      disease severity and the depression in FM.

PMID- 20676643
TI  - Current, new and future treatments of osteoporosis.
AB  - Osteoporosis as a common chronic disease is challenging human health. Although
      different therapeutic options are routinely used for prevention/treatment of
      osteoporosis, their side effects and benefits are under question. Increasing our
      knowledge about signaling pathways in bone and osteocytes as well as osteoblasts
      and osteoclasts will help us in designing new therapeutic modalities for
      osteoporosis. In the present study, all new therapeutic measures of osteoporosis
      have been reviewed. For this purpose, search engines like Pubmed, Web of Science,
      Scopus, Google Scholar were searched and all relevant articles were found. The
      study was limited to the year 1998-2010. Bisphosphonates are the cornerstone of
      osteoporosis treatment, but there are not enough relevant studies that
      investigated their equivalencies in comparison with each other or the other
      medications. Therefore, medication selection is empirical and subjective.
      Furthermore, no eminent study has compared certain combinations. There are new
      hopes for treatment of osteoporosis, which are more specific with less harm. Our
      results show that new and emerging therapies are more potent and target specified
      which more individualize osteoporosis treatment; however, more investigations on
      their safety and efficacy in comparison with current medications are highly
      recommended.

PMID- 20676645
TI  - White cells count in smokers affected by rheumatic diseases.
AB  - Evidence shows that tobacco smoking interacts with development of rheumatic
      diseases. Increase in white cells count (leukocytosis) is frequently present, and
      in smokers, it is considered a biomarker of cardiovascular risk. Aim of the study
      is to evaluate this biomarker in smokers with rheumatic diagnosis. We carried out
      an observational study on 115 rheumatic outpatients (26 men and 89 women) divided
      into two groups according to their smoking habit: one composed of 56 smokers, the
      other of 59 not smokers. Diagnosis and common routinary clinical parameters were
      collected. In the total sample, smokers were 48.69%. Most common diagnosis was
      osteoarthritis (OA) (40.87% of the total); smokers in OA women were 36.11%,
      smokers in OA men were 54.55%. Second most common diagnosis was rheumatoid
      arthritis (RA) (23.48% of the total); smokers in RA women were 40.91%; smokers in
      RA men were 80%. OA smokers showed a significant increase (P < 0.05) in white
      cells count when compared with OA not smokers. Between RA smokers and not
      smokers, any clinical difference was found. RA subjects following regular
      pharmacological treatment in the last 2 months were 84.61%. OA patients treated
      with drugs in the last 2 months were only 22.2%. Results seem to confirm that
      smoking habit may influence the development as well as gender distribution of
      rheumatic diseases. They show also that in absence of pharmacological treatment
      in smokers affected by OA leukocytosis (biomarker of cardiovascular risk) is
      observed.

PMID- 20676647
TI  - Echinococcus multilocularis infection and TNF inhibitor treatment in a patient
      with rheumatoid arthritis.

PMID- 20676646
TI  - Short- and long-term results of clinical effectiveness of sodium hyaluronate
      injection in supraspinatus tendinitis.
AB  - The objective of the study is to evaluate the short- and long-term effect of
      intraarticular sodium hyaluronate (SH) application in patients diagnosed with
      supraspinatus tendinitis (ST) that have shoulder pain on the clinical symptoms of
      the patients through comparison with conventional physiotherapy methods. A total
      of 24 patients were included in the study and were randomized into two groups.SH
      injection and physical therapy modalities (PTM) were administered to Group I and
      Group II, respectively. Home exercise programs were recommended to all of the
      patients in both groups. The patients were evaluated using the pain severity
      [Visual Analog Scale (VAS)], range of motion and functional evaluation (FE)
      parameters pertaining to pre-treatment, 3rd week, 3rd month and 4th year post
      treatment. Patient's global effectiveness (PGE) evaluation was performed in the
      3rd month and 4th year of the treatment. There were no statistically significant
      differences for Group I's resting VAS value between pre-treatment controls and
      controls in the 3rd week and 3rd month, no statistically significant differences
      were detected for Group II in passive flexion between pre-treatment and the 4th
      year, also in passive external rotation between pre-treatment and 3rd week (P >
      0.05). A statistically significant recovery was detected in both groups in all
      the other evaluation parameters (P < 0.05). When evaluation was performed among
      groups, active abduction in the control in the 3rd month, VAS by movement and a
      statistically significant difference in favor of Group I in FE were determined (P
      < 0.05). No statistically significant differences were found among groups in PGE
      (P > 0.05). It was concluded that physical therapy modalities and SH application
      supplemented by home exercise programs were similar effects in short- and long
      term for ST which causes pain in shoulder and SH application may be a better
      alternative with regard to effectiveness and side effects for other treatment
      methods applied intraarticulary.

PMID- 20676648
TI  - Factors and comorbidities associated with central nervous system involvement in
      systemic lupus erythematosus: a retrospective cross-sectional case-control study
      from a single center.
AB  - To evaluate, by a retrospective cross-sectional case-control study from a single
      center, the distribution of a number of factors and comorbidities potentially
      related to central nervous system involvement in SLE Italian patients, a number
      of "generic" (i.e. not strictly SLE related) and "specific" (i.e. SLE related)
      risk factors were checked and their distribution analyzed in SLE patients with
      (NPSLE) and without (SLE) neuropsychiatric (NP) involvement. One hundred and
      fifty-three SLE patients with NP involvement observed from 1999 to 2008 and 247
      SLE patients without NP manifestations, matched for sex, age and disease duration
      were included in the study. A neuropsychiatric (NP) event represented the
      heralding symptom of the disease in 40.5% of NPSLE. Headache, cerebrovascular
      events, mood disorders and seizures were the most frequent NP manifestations.
      NPSLE patients had a major cumulative number of the investigated factors than
      controls without NP involvement. Antiphospholipid antibodies (aPL), lupus
      anticoagulant (LA), Antiphospholipid antibodies syndrome (APS), Raynaud's
      phenomenon, smoke, assumption of contraceptives and higher cumulative dose of
      glucocorticosteroids (GC) were significantly more commonly observed among NPSLE.
      APS and systemic arterial hypertension were more frequently detected among
      patients with focal NP manifestations, especially cerebrovascular events. aPL,
      LA, APS, Raynaud's phenomenon, smoke, contraceptives intake and higher cumulative
      dose of GC did prove more frequently detected in NPSLE patients than in controls.
      In particular, overall, arterial hypertension should be regarded as a potential
      independent "risk factor" for focal involvement, especially for cerebrovascular
      events.

PMID- 20676649
TI  - Relation of plasma total homocysteine, folate and vitamin B12 levels to bone
      mineral density in Moroccan healthy postmenopausal women.
AB  - To test whether in Moroccan healthy postmenopausal women, levels of plasma total
      homocysteine (tHcy), folate, and vitamin B12 are related to BMD. A total of 188
      volunteer postmenopausal women were recruited from our blood taking center
      between April 2008 and December 2008. Each subject completed a standardized
      questionnaire designed to document putative risk factors of osteoporosis. Bone
      mineral density was determined by a Lunar Prodigy Vision DXA system, and blood
      samples for plasma tHcy, folate, vitamin B12, and serum parathyroid hormone (PTH)
      were taken. Comparison between women with osteoporosis, osteopenia and normal BMD
      showed that the osteoporotic women were significantly older, had lower weight and
      height than the women of the other groups. Plasma tHcy was significantly higher
      in the osteoporotic group. Levels of tHcy were inversely related to BMD at the
      lumbar spine, at the total hip and plasma vitamin B12 and positively related to
      age and creatinine. Multiple regression analysis showed that age and BMI were the
      main predictors of BMD at the lumbar spine, whereas the main predictors of BMD at
      the total hip were age, BMI, plasma tHcy, and plasma vitamin B(12). tHcy and
      vitamin B12 are independent risk factors for osteoporosis in Moroccan healthy
      postmenopausal women.

PMID- 20676651
TI  - Letter to the Editor re: superselective arterial embolisation with a liquid
      polyvinyl alcohol copolymer in patients with acute gastrointestinal haemorrhage.

PMID- 20676650
TI  - MBD4 gene is associated with rheumatoid arthritis in Chinese patients in Taiwan.
AB  - This study examines whether or not MBD4 polymorphism is a marker for rheumatoid
      arthritis (RA) susceptibility or severity for Chinese patients in Taiwan. This
      study included 193 patients with RA, while 190 unrelated healthy individuals
      living in Central Taiwan served as controls. The relationship between MBD4
      polymorphism and clinical manifestations of RA was evaluated. For the genotype
      and allelic frequency of MBD4-1057 polymorphism, there were no statistically
      significant differences between patients with RA and controls. There were
      significant differences in the distribution of MBD4-8666 polymorphism frequencies
      between patients with RA and controls [P = 0.013; P (corrected) (Pc) = 0.039].
      There were also significant relationships in the distribution of MBD4-9229
      polymorphism genotype between patients with RA and controls (P = 0.007; Pc =
      0.021). However, we did not detect any associations for MBD4-1057, MBD4-8666 or
      MBD4-9229 with rheumatoid factor presence, extra-articular involvement or bone
      erosion in patients with RA. Results suggest that MBD4-8666 and MBD4-9229, but
      not MBD4-1057, gene polymorphisms are related to RA in Chinese patients in
      Taiwan.

PMID- 20676652
TI  - Self-gating MR imaging of the fetal heart: comparison with real cardiac
      triggering.
AB  - PURPOSE: To investigate the self-gating technique for MR imaging of the fetal
      heart in a sheep model. MATERIAL AND METHODS: MR images of 6 fetal sheep heart
      were obtained at 1.5 T. For self-gating MRI of the fetal heart a cine SSFP in
      short axis, two and four chamber view was used. Self-gated images were compared
      with real cardiac triggered MR images (pulse-wave triggering). MRI of the fetal
      heart was performed using both techniques simultaneously. Image quality was
      assessed and the left ventricular volume and function were measured and compared.
      RESULTS: Compared with pulse-wave triggering, the self-gating technique produced
      slightly inferior images with artifacts. Especially the atrial septum could not
      be so clearly depicted. The contraction of the fetal heart was shown in cine
      sequences in both techniques. The average blood volumes could be measured with
      both techniques with no significant difference: at end-systole 3.1 ml (SD+/-0.2),
      at end-diastole 4.9 ml (+/-0.2), with ejection fractions at 38.6%, respectively
      39%. CONCLUSION: Both self-gating and pulse-wave triggered cardiac MRI of the
      fetal heart allowed the evaluation of anatomical structures and functional
      information. Images obtained by self-gating technique were slightly inferior than
      the pulse-wave triggered MRI.

PMID- 20676653
TI  - Toward cardiovascular MRI at 7 T: clinical needs, technical solutions and
      research promises.
AB  - OBJECTIVE: To consider potential clinical needs, technical solutions and research
      promises of ultrahigh-field strength cardiovascular MR (CMR). METHODS: A
      literature review is given, surveying advantages and disadvantages of CMR at
      ultrahigh fields (UHF). Key concepts, emerging technologies, practical
      considerations and applications of UHF CMR are provided. Examples of UHF CMR
      imaging strategies and their added value are demonstrated, including the numerous
      unsolved problems. A concluding section explores future directions in UHF CMR.
      RESULTS: UHF CMR can be regarded as one of the most challenging MRI applications.
      Image quality achievable at UHF is not always exclusively defined by signal-to
      noise considerations. Some of the inherent advantages of UHF MRI are offset by
      practical challenges. But UHF CMR can boast advantages over its kindred lower
      field counterparts by trading the traits of high magnetic fields for increased
      temporal and/or spatial resolution. CONCLUSIONS: CMR at ultrahigh-field strengths
      is a powerful motivator, since speed and signal may be invested to overcome the
      fundamental constraints that continue to hamper traditional CMR. If practical
      challenges can be overcome, UHF CMR will help to open the door to new approaches
      for basic science and clinical research.

PMID- 20676654
TI  - The energy cost of embryonic development in fishes and amphibians, with emphasis
      on new data from the Australian lungfish, Neoceratodus forsteri.
AB  - The rate of oxygen consumption throughout embryonic development is used to
      indirectly determine the 'cost' of development, which includes both
      differentiation and growth. This cost is affected by temperature and the duration
      of incubation in anamniote fish and amphibian embryos. The influences of
      temperature on embryonic development rate, respiration rate and energetics were
      investigated in the Australian lungfish, Neoceratodus forsteri, and compared with
      published data. Developmental stage and oxygen consumption rate were measured
      until hatching, upon which wet and dry gut-free masses were determined. A measure
      of the cost of development, the total oxygen required to produce 1 mg of
      embryonic dry tissue, increased as temperature decreased. The relationship
      between the oxygen cost of development (C, ml mg(-1)) and dry hatchling mass (M,
      mg) in fishes and amphibians is described by C = 0.30 M(0.22 0.13 (95% CI)), r
      (2) = 0.52. The scaling exponent indicates that the cost of embryonic development
      increases disproportionally with increasing hatchling mass. At 15 and 20 degrees
      C, N. forsteri cost of development is significantly lower than the regression
      mean for all species, and at 25 degrees C is lower than the allometrically scaled
      data set. Unexpectedly, incubation of N. forsteri is long, despite natural
      development under relatively warm conditions, and may be related to a large
      genome size. The low cost of development may be associated with construction of a
      rather sluggish fish with a low capacity for aerobic metabolism. The metabolic
      rate is lower in N. forsteri hatchlings than in any other fishes or amphibians at
      the same temperature, which matches the extremely low aerobic metabolic scope of
      the juveniles.

PMID- 20676655
TI  - Pascual-Castroviejo type II syndrome (P-CIIS). Importance of the presence of
      persistent embryonic arteries.
AB  - INTRODUCTION: Cutaneous hemangioma and vascular malformation are two vascular
      abnormalities frequently associated with absence or hypoplasia of one or both
      carotid and/or vertebral arteries, presence of persistent embryonic arteries,
      especially the trigeminal, cerebellar malformations, and coarctation of the
      aortic arch and/or congenital cardiopathy. This disease is known as Pascual
      Castroviejo type II syndrome (P-CIIS) and by the acronym PHACE. MATERIAL AND
      METHODS: Three patients (two females and one male) with facial hemangioma are
      studied during the first years of age by magnetic resonance angiography (MRA) and
      their vascular evolution to adult age followed through several MRA controls.
      RESULTS: All the three patients showed persistence of the trigeminal artery
      associated to other intra- and extracranial vascular abnormalities of type
      hemangioma or hemangiomatous arteries that presented progressive involution with
      decreased arterial caliber without appearing cerebrovascular stroke or hypoxic
      zones because, at the same time, collateral vascularization appeared through
      connections between the embryonic arteries and the peripheral branches of the
      internal carotids or connections between branches of the external and internal
      carotids. Only one patient had obstruction of a branch of the left middle
      cerebral artery after 3 days, with gastroenteritis with elevated fever at 17
      months of life that caused parenchymal infarct in the left cerebral region
      supplied by the obstructed artery. CONCLUSIONS: The presence of embryonic
      arteries, especially the trigeminal, and connections between branches of the
      internal and external carotids, mainly through the internal maxillary and
      ophthalmic arteries, ensure the cerebral supply in the P-CIIS despite the
      progressive involvement of the cerebral arteries.

PMID- 20676657
TI  - Endoanal ultrasound for anal cancer follow up.

PMID- 20676658
TI  - CARD15 mutations and colorectal cancer in a South European country.
AB  - PURPOSE: CARD15 mutations are associated with higher susceptibility to Crohn's
      disease (CD) and longstanding colonic CD increases the risk of developing
      colorectal cancer (CRC). The relation between these mutations and sporadic CRC
      remains controversial. The aim of this study was to assess whether germline
      and/or somatic CARD15 mutations are risk factors for sporadic CRC in Portugal and
      whether there are genotype-phenotype correlations in these patients. METHODS: The
      three main CARD15 mutations (R702W, G908R and 3020insC) were researched in 112
      sporadic CRC patients and 152 healthy subjects. RESULTS: Overall, CARD15
      mutations were found in 18 patients (16.1%) and in 15 controls (9.9%; p = 0.132).
      Individually, the incidence of R702W was significantly higher in patients than in
      controls (12.5% vs. 5.3%, p = 0.035), whereas the genotype frequencies for G908R
      (2.7% vs. 3.3%) and 3020insC (0.9% vs. 1.3%) were not statistically different
      between the two groups. Entire genotypic agreement was found in patients
      genotyped for blood and neoplastic DNA. A significantly higher incidence of
      CARD15 mutations was detected in patients with CRC diagnosed under 60 years old
      (28.6% vs. 10.4%, p = 0.015) and in female patients (24.4% vs. 10.4%, p = 0.048).
      No associations were found between CARD15 mutations and family history, symptoms
      or CRC pathologic characteristics. CONCLUSIONS: The CARD15 R702W variant might be
      a predisposing factor to sporadic CRC in Portugal, particularly in patients under
      60-years old and in female patients. This susceptibility appears to be linked
      with germline CARD15 mutations. Nevertheless, we have found no evidence that
      CARD15 mutations predict the pathologic characteristics of CRC.

PMID- 20676659
TI  - Population-based screening for colorectal cancer with faecal occult blood test-
      do we really have enough evidence?
AB  - INTRODUCTION: Population-based randomised controlled trials (RCT) have shown that
      invitation to biennial screening with faecal occult blood testing (FOBT) during
      10 or more years reduced colorectal cancer-specific mortality. These results have
      stimulated plans to introduce mass screening in various countries; however, none
      of these trials has been able to show any reduction of total mortality, which
      should be expected with reduced disease-specific mortality in a RCT. METHODS: The
      aim of this review is to analyse, in more detail, the findings in these trials.
      The results of the trials have, in this review, been systematised and discussed
      in the context of potential bias, validity and effectiveness. RESULTS: It is
      found that the reduced cancer-specific mortality is modest and that the clinical
      significance may be discussed. The number of persons needed to be invited for
      multiple screening rounds to avoid one death in colorectal cancer (CRC) is high,
      ranging from about 600 to 1,200. A remarkable finding is that only one fourth of
      the carcinomas in those invited to the screening were actually detected by this
      intervention. The absence of reduced total mortality in all series is a serious
      problem and evokes questions about the validity in determination of cause of
      death. None of these trials showed any effect on incidence of CRC by removal of
      precancerous adenomas. CONCLUSIONS: It seems reasonable to conclude that the
      scientific evidence to support introduction of population-based screening
      programmes with FOBT appears not yet strong enough. In addition, harm/benefit and
      cost/effectiveness ratios are not well determined.

PMID- 20676660
TI  - A rare cause for peritonitis: pancreatic heterotopia.

PMID- 20676661
TI  - Necrotising fasciitis secondary to intra-abdominal sepsis.

PMID- 20676662
TI  - Pathological examination of 12 regional lymph nodes and long-term survival in
      stages I-III colon cancer patients: an analysis of 2,056 consecutive patients in
      two branches of same institution.
AB  - PURPOSE: Pathologic examination of at least 12 lymph nodes (LNs) is widely
      accepted as a standard for colon cancer surgery. We sought to address its
      association with patient source, other clinicopathological factors, and survival
      by comparing information from two branches in a large single institution.
      METHODS: Patients with stages I-III adenocarcinoma of the colon between 1998 and
      2003 were identified from the Chang Gung Colorectal Tumor Registry in two
      branches (Linkou and Kaohsiung branches) of same institution. We used
      multivariate analysis to adjust for variables with P < 0.1 in univariate
      analyses. RESULTS: A minimum of 12 examined nodes were observed in 80% of
      patients in Linkou branch versus 25% in Kaohsiung branch (P < 0.0001). Younger
      age, right hemicolectomy, larger tumor, higher tumor stage, higher caseload of
      surgeons, and patients at Linkou branch with an odds ratio (OR) as high as 23
      (95% CI, 17-31) were independently associated with a higher frequency of >=12
      examined nodes. Patients with examined node number of <12 had a greater risk of
      recurrence within stages II and III (stage II: adjusted OR 1.88, 95% CI 1.27
      2.79; stage III: adjusted OR 1.58, 95% CI 1.15-2.17) but not within stage I (OR
      0.73, 95% CI 0.23-2.24). CONCLUSIONS: The results confirm that factors
      influencing nodal harvest are multifactorial and the examined LN number of 12 or
      more is associated with an increased long-term survival in stages II-III colon
      cancer. It is possible to adequately sample and examine a sufficient number of
      nodes in the majority of colon cancer specimens by standardized conventional
      methods.

PMID- 20676663
TI  - Co-morbidity and postsurgical outcome in patients with perforated sigmoid
      diverticulitis.
AB  - INTRODUCTION: It was previously reported that in patients with acute perforated
      diverticulitis with Hinchey categories I to III sigmoidectomy with primary
      anastomosis (PA) is superior to Hartmann's procedure (HP) as later closure of
      colostomy involves substantial morbidity. We evaluated our experience with PA for
      patients with perforated diverticulitis over a 10-year period and aimed to
      investigate whether Hinchey category or co-morbidity are more relevant for
      postoperative outcome. METHODS: Records of all patients treated at our
      institution for sigmoid diverticulitis between 1996 and 2006 were retrieved from
      an in-hospital database (N = 787, median age 66 years, range 30 to 94,
      female:male ratio 1.3:1); 73 patients who underwent immediate emergency surgery
      for perforated diverticulitis were included in this study. American Society of
      Anesthesiology (ASA) classification to gauge co-morbidity and Hinchey category
      for intraoperative extent of inflammation were evaluated as regards their
      relevance for postoperative mortality and major complications. RESULTS: 47
      patients (64%) underwent sigmoid colectomy and PA, which was combined with loop
      ileostomy in 11 patients (15%). Sigmoid colectomy and HP was performed in 26
      patients (36%). Major postoperative complications occurred in 26 patients (36%).
      In the PA group, 10 of 47 patients (21%) had anastomotic leakage. Three leakages
      occurred despite a loop ileostomy. Anastomotic leakage was independent of Hinchey
      category (Hinchey I: three patients, Hinchey II: four patients, Hinchey III:
      three patients, n.s.), but associated with co-morbidity (one patient ASA II, six
      patients ASA III, three patients ASA IV, P < 0.05). Total mortality was 12%.
      Seven patients died after HP and two patients after PA. No mortality was observed
      in PA patients with loop ileostomy. CONCLUSIONS: Emergency surgery for perforated
      sigmoid diverticulitis is associated with high morbidity and mortality rates.
      Anastomotic leakage was associated with patient co-morbidity rather than with
      intraoperative Hinchey category, suggesting that the decision to perform PA
      should better be based on patient's general condition rather than on
      intraoperative extent of inflammation.

PMID- 20676664
TI  - [Registry and studies of the German Competence Network on Atrial Fibrillation
      (AFNET)].
AB  - The German Competence Network on Atrial Fibrillation (AFNET) is a national
      interdisciplinary research network funded by the Federal Ministry of Education
      and Research (BMBF). AFNET was initiated in 2003 and aims at improving treatment
      of atrial fibrillation (AF), the most frequent sustained cardiac arrhythmia.
      AFNET has established a nationwide patient registry on diagnostics, therapy,
      course and complications of AF in Germany. The data analyzed to date demonstrate
      that patients with AF are likely to have multiple co-morbidities, such as
      hypertension, valvular heart disease, coronary artery disease, diabetes mellitus
      and advanced age. Oral anticoagulation is provided to the majority of patients in
      accordance with the recommendations given by guidelines. Further areas of
      research deal with the optimal duration of antiarrhythmic therapy following
      electrical cardioversion of atrial fibrillation and the value of strategies to
      prevent arrhythmogenic changes, such as fibrosis in the atria, for prevention of
      further episodes of atrial fibrillation. Additional registry projects were
      established for patients with catheter-based interventional therapy of atrial
      fibrillation and surgical ablation to define success, complications and long term
      results of these recently developed procedures more clearly. Data and insights
      gathered from these projects were used to further develop standards of care in
      two international conferences.

PMID- 20676665
TI  - Combining the categorical and the dimensional perspective in a diagnostic map of
      psychotic disorders.
AB  - We introduce a diagnostic map that was calculated by robust non-metric
      multidimensional scaling based on AMDP symptom profiles of patients with
      schizophrenic and affective disorders to demonstrate a possibility to combine the
      categorical and the dimensional perspective at the same time. In the diagnostic
      map, a manic, a depressive, and a non-affective cluster clearly emerged. At the
      same time, the mania dimension (r = 0.82), the depression dimension (r = 0.68),
      and the apathy dimension (r = 0.74) showed high multiple regression values in the
      map. We found substantial overlaps of the diagnostic groups with regard to the
      affective spectrum but irrespective of the ICD-10 classification. Within this
      sample, we found the association and quality of mood symptoms to be a structuring
      principle in a diagnostic map. We demonstrate that this approach represents a
      promising way of combining the categorical and the dimensional perspective. As a
      practical implementation of these findings, a multidimensional diagnostic map
      could serve as an automated diagnostic tool based on psychopathological symptom
      profiles.

PMID- 20676666
TI  - The impact of pulmonary disease on noninvasive measurement of cardiac output by
      the inert gas rebreathing method.
AB  - Cardiac output (CO) is an important parameter for diagnosis and therapy of heart
      diseases, but it is still difficult to determine. Innocor, a novel noninvasive
      inert gas rebreathing (IGR) system, has shown promising results. However, the
      impact of pulmonary diseases on IGR remains unclear. The aim of the study
      therefore was to assess the accuracy and reliability of IGR in patients with
      distinct chronic lung disease. A total of 96 patients were enrolled, including 48
      consecutive patients with variant lung diseases (group A) and 48 pair-matched
      pulmonary healthy patients (group B). CO was measured with cardiac magnetic
      resonance imaging (CMR) and IGR. Lung function testing was done by spirometry
      [FEV(1)/FVC (forced expiratory volume in one second/forced vital capacity), VC
      (vital capacity)] and determination of the diffusing capacity of the lung for
      carbon monoxide divided by alveolar volume (DLCO/VA). In group A we found a mean
      CO of 4.7 +/- 1.3 L/min by IGR and 4.9 +/- 1.2 L/min by CMR. Group B showed a
      mean CO of 4.8 +/- 1.4 L/min by IGR and 5.0 +/- 1.3 L/min by CMR. Bland-Altman
      analysis revealed good correspondence between CMR and IGR, with an average
      deviation of 0.1 +/- 1.0 L/min in group A and 0.1 +/- 1.0 L/min in group B (p =
      0.99). Multiple regression analysis for the pulmonary parameters did not show a
      statistically significant impact on the mean bias of CO measurements (FEV(1)/FVC:
      r = 0.01, p = 0.91; VC: r = -0.2, p = 0.13; and DLCO/VA: r = 0.04, p = 0.82). IGR
      allows a feasible determination of CO even in patients with lung diseases. The
      accuracy of the IGR method is not influenced by either pulmonary obstructive and
      restrictive diseases or a reduced DLCO.

PMID- 20676667
TI  - FANCJ/BRIP1 recruitment and regulation of FANCD2 in DNA damage responses.
AB  - FANCJ/BRIP1 encodes a helicase that has been implicated in the maintenance of
      genomic stability. Here, to better understand FANCJ function in DNA damage
      responses, we have examined the regulation of its cellular localization. FANCJ
      nuclear foci assemble spontaneously during S phase and are induced by various
      stresses. FANCJ foci colocalize with the replication fork following treatment
      with hydroxyurea, but not spontaneously. Using FANCJ mutants, we find that FANCJ
      helicase activity and the capacity to bind BRCA1 are both involved in FANCJ
      recruitment. Given similarities to the recruitment of another Fanconi anemia
      protein, FANCD2, we tested for colocalization of FANCJ and FANCD2. Importantly,
      these proteins show substantial colocalization, and FANCJ promotes the assembly
      of FANCD2 nuclear foci. This process is linked to the proper localization of
      FANCJ itself since both FANCJ and FANCD2 nuclear foci are compromised by FANCJ
      mutants that abrogate its helicase activity or interaction with BRCA1. Our
      results suggest that FANCJ is recruited in response to replication stress and
      that FANCJ/BRIP1 may serve to link FANCD2 to BRCA1.

PMID- 20676668
TI  - Chemical impurities and contaminants in different silicone oils in human eyes
      before and after prolonged use.
AB  - BACKGROUND: Intraocular silicone oil (SiO) impurities as low molecular weight
      components (LMWC) and residual catalysts are thought to cause ocular toxicity. A
      case-control study was initiated to determine if highly purified SiOs of equal
      viscosity from two different manufacturers had a similar chemical stability after
      prolonged clinical use as a vitreous substitute in patients. METHODS: Medical
      grade samples of AcriSilOl 5000 (ASO 5000) and Vitreocrom 5000 (VC 5000) were
      obtained. Gas chromatography/flame ionisation detection (GC/FID) analyses were
      used to detect and characterize the LMWC (D4-D7 Siloxane fractions) and quantify
      the cholesterol level in the extracted SiOs as well as in the original SiO
      samples. RESULTS: The concentration levels of LMWC D4 and D7 fractions of the
      original SiO samples already showed a significant difference (p < 0.05)
      preoperatively. After removal, SiO samples of ASO 5000 showed an absolute and
      relative decrease in all LMWC concentrations, except for the D6 values. Samples
      of VC 5000 had a significant decrease in the mean D4 concentration level, whereas
      the mean D5, D6, D7, and total LMWC values increased. The cholesterol increased
      as well within all SiO probes, but no significant differences between the two SiO
      types were found. CONCLUSIONS: As cholesterol concentrations increased and LMWC
      D4 decreased similarly in both SiO brands, their stability might be regarded as
      equal. The smallest LMWC molecules (D4) appear to have the greatest capability to
      diffuse into the surrounding ocular tissues. The low grade of emulsification
      (12.9 %) in our patients could not be related to LMWC or cholesterol changes.

PMID- 20676669
TI  - The change in internal aberrations following myopic corneal laser refractive
      surgery.
AB  - BACKGROUND: In virgin eyes, the internal aberrations compensate corneal
      aberrations, and it has been suggested that the compensation may be feedback
      driven and developmental, with active or passive adaptive mechanisms potentially
      responsible for the aberration auto-compensation. The purpose of this study is to
      investigate the internal higher order aberrations (HOA) following laser in situ
      keratomileusis (LASIK). METHODS: Prospective corneal and internal HOA were
      measured pre-operatively and 6 months post-operatively on 50 consecutive LASIK
      patients with the OPD-Scan. RESULTS: There were increases to corneal HOA terms
      Z04 (0.215 +/- 0.092 MUm to 0.381 +/- 0.180 MUm), Z06 (0.002 +/- 0.018 MUm to
      0.049 +/- 0.034 MUm) and Z46 (0.010 +/- 0.017 MUm to 0.018 +/- 0.016 MUm) with
      corresponding increases to internal HOA terms Z04 (-0.176 +/- 0.102 MUm to -0.218
      +/- 0.121 MUm), Z06 (0.004 +/- 0.022 MUm to -0.010 +/- 0.036 MUm) and Z46 (0.008
      +/- 0.106 MUm to -0.015 +/- 0.054 MUm). The increases in internal aberrations
      attenuated the increase in corneal aberrations, providing an overall lower
      quantity of total aberration. A greater increase in corneal spherical aberration
      and associated compensation was found to occur with greater degrees of attempted
      myopic correction. CONCLUSION: Corneal spherical aberration and Z46increased with
      corresponding increases in the internal spherical aberration and Z46 following
      LASIK. This may be an active compensatory mechanism of the internal optics to
      change, in order to reduce the effect of induced corneal HOA.

PMID- 20676670
TI  - Intravitreal ranibizumab, photodynamic therapy, and vitreous surgery for the
      treatment of juxtapapillary retinal capillary hemangioma.

PMID- 20676671
TI  - Mapping of BrdU label-retaining dental pulp cells in growing teeth and their
      regenerative capacity after injuries.
AB  - Recent studies have demonstrated that human dental pulp contains adult stem
      cells. A pulse of the thymidine analog BrdU given to young animals at the optimal
      time could clarify where slow-cycling long-term label-retaining cells (LRCs),
      putative adult stem cells, reside in the pulp tissue. This study focuses on the
      mapping of LRCs in growing teeth and their regenerative capacity after tooth
      injuries. Two to seven peritoneal injections of BrdU into pregnant Wistar rats
      revealed slow-cycling long-term dense LRCs in the mature tissues of born animals.
      Numerous dense LRCs were postnatally decreased in number and reached a plateau at
      4 weeks after birth when they mainly resided in the center of the dental pulp,
      associating with blood vessels. Mature dental pulp cells were stained with
      Hoechst 33342 and sorted into (<0.76%) side population cells using FACS, which
      included dense LRCs. Some dense LRCs co-expressed mesenchymal stem cell markers
      such as STRO-1 or CD146. Tooth injuries caused degeneration of the odontoblast
      layer, and newly differentiated odontoblast-like cells contained LRCs. Thus,
      dense LRCs in mature pulp tissues were supposed to be dental pulp stem cells
      possessing regenerative capacity for forming newly differentiated odontoblast
      like cells. The present study proposes the new hypothesis that both granular and
      dense LRCs are equipped in the dental pulp and that the dense LRCs with
      proliferative capacity play crucial roles in the pulpal healing process following
      exogenous stimuli in cooperation with the granular LRCs.

PMID- 20676672
TI  - Functional consequences of Kir2.1/Kir2.2 subunit heteromerization.
AB  - Kir2 subunits form channels that underlie classical strongly inwardly rectifying
      potassium currents. While homomeric Kir2 channels display a number of distinct
      and physiologically important properties, the functional properties of
      heteromeric Kir2 assemblies, as well as the stoichiometries and the arrangements
      of Kir2 subunits in native channels, remain largely unknown. Therefore, we have
      implemented a concatemeric approach, whereby all four cloned Kir2 subunits were
      linked in tandem, in order to study the effects of Kir2.1 and Kir2.2
      heteromerization on properties of the resulting channels. Kir2.2 subunits
      contributed stronger to single-channel conductance than Kir2.1 subunits, and
      channels containing two or more Kir2.2 subunits displayed conductances
      indistinguishable from that of a Kir2.2 homomeric channel. In contrast, single
      channel kinetics was a more discriminating property. The open times were
      significantly shorter in Kir2.2 channels compared with Kir2.1 channels and
      decreased nearly proportionally to the number of Kir2.2 subunits in the
      heteromeric channel. Similarly, the sensitivity to block by barium also depended
      on the proportions of Kir2.1 to Kir2.2 subunits. Overall, the results showed that
      Kir2.1 and Kir2.2 subunits exert neither a dominant nor an anomalous effect on
      any of the properties of heteromeric channels. The data highlight opportunities
      and challenges of using differential properties of Kir2 channels in deciphering
      the subunit composition of native inwardly rectifying potassium currents.

PMID- 20676674
TI  - Phase I, pharmacokinetic, and biological studies of TSU-68, a novel multiple
      receptor tyrosine kinase inhibitor, administered after meals with solid tumors.
AB  - PURPOSE: TSU-68 is a low molecular weight inhibitor of the tyrosine kinases for
      vascular endothelial growth factor receptor 2, platelet-derived growth factor
      receptor beta, and fibroblast growth factors receptor 1. In this study, we
      assessed the recommended dose with TSU-68 administration of twice-daily (b.i.d.)
      or thrice-daily (t.i.d.) after meals for 4 weeks in Japanese patients with solid
      tumors based on the safety and tolerability and investigated the relationship
      between angiogenesis biomarker and clinical outcomes. METHODS: The study design
      was a dose-escalation method with alternating enrollment of b.i.d. administration
      and t.i.d. administration after meal by traditional three-patient cohort.
      RESULTS: We enrolled 24 patients at doses of 200, 400, and 500 mg/m(2) b.i.d. or
      200 and 400 mg/m(2) t.i.d. No dose-limiting toxicity (DLT) occurred in the 200
      mg/m(2) b.i.d. or t.i.d., and 3 patients experienced DLTs at 400 mg/m(2) b.i.d.
      or 400 mg/m(2) t.i.d. As main toxicity, blood albumin decreased, malaise,
      diarrhea, alkaline phosphatase increased, anorexia, abdominal pain, nausea, and
      vomiting were observed as almost all grade 1-2. There were no apparent
      differences in pharmacokinetic parameters between days 2 and 28 after the
      repeated b.i.d. and t.i.d. doses. Although tumor shrinkage was not observed, the
      disease control rate was 41.7%. As an angiogenesis-related factor of stratified
      analysis, plasma vascular endothelial growth factor and plasminogen activator
      inhibitor-1 were detected as a significant increase with progressive disease
      patients. CONCLUSIONS: A recommended dosage of TSU-68 for this administration
      schedules was estimated to be 400 mg/m(2) or less b.i.d.

PMID- 20676675
TI  - Phase I and pharmacokinetic study of TSU-68, a novel multiple receptor tyrosine
      kinase inhibitor, by twice daily oral administration between meals in patients
      with advanced solid tumors.
AB  - PURPOSE: A single-agent dose-escalating phase I and pharmacokinetic study on TSU
      68, a novel multiple receptor tyrosine kinase inhibitor, was performed to
      determine the safety profile, maximum-tolerated dose for Japanese patients with
      advanced solid tumors and to define the recommended dose of phase II studies.
      METHODS: Study design was a dose escalation method on a three-patient cohort. TSU
      68 was given orally twice daily (bid) between meals without interruption; the
      estimation of dose escalation was based on the toxicity within 4 week
      administration at each dose level. RESULTS: Fifteen patients were enrolled into
      the study. Dose levels studied were 200, 400, 800, and 1,200 mg/m(2) bid. Grade 3
      arrhythmia and anemia/thrombocytopenia were observed in 1 patient each at 800
      mg/m(2) bid. Three patients discontinued continuous oral administration for 4
      weeks at 400 and 800 mg/m(2) bid. At 1,200 mg/m(2) bid, 2 patients discontinued
      the treatment over 4 weeks for intolerable fatigue and abdominal pain,
      respectively. No serious drug-related toxicities have been observed. Grade 1-2
      toxicity included urinary/feces discoloration, diarrhea, fatigue, anorexia,
      abdominal/chest pain, and edema. Tumor shrinkage was observed in 1 patient of
      NSCLC. In the pharmacokinetics, at any dose levels, C(max) and AUC(0-t) after
      repeated administration of TSU-68 on days 8 and 29 were ~2-fold lower that those
      after the first administration on day 1; these parameters are similar between
      days 8 and 28. In addition, no obvious dose-dependent increase in plasma exposure
      to TSU-68 repeatedly administered was observed over the four dose levels,
      including the higher dose levels. CONCLUSIONS: The tolerable dose in this
      administration schedule for continuing treatment is thought to be 800 mg/m(2) or
      less bid.

PMID- 20676676
TI  - Phase II study of short-course capecitabine plus oxaliplatin (XELOX) followed by
      maintenance capecitabine in advanced colorectal cancer: XelQuali study.
AB  - PURPOSE: To evaluate the efficacy, safety and quality of life of a short course
      of oxaliplatin plus capecitabine (XELOX) followed by single-agent capecitabine in
      patients with previously untreated, inoperable, metastatic colorectal cancer.
      METHODS: Patients received intravenous oxaliplatin 130 mg/m(2) on d1 plus oral
      capecitabine 1,000 mg/m(2) twice daily (bid) on d1-14 every 21 days for four
      cycles. Patients achieving stable disease (SD) or better than received
      capecitabine 1,250 mg/m(2) bid on d1-14 every 21 days until disease progression.
      The primary endpoint was progression-free survival (PFS). RESULTS: Overall, 21/45
      (47%) of patients responded to the initial XELOX chemotherapy whilst SD or better
      was documented in 76%. Median PFS was 6.7 (95% CI 5.7-9.6) months, and median
      overall survival (OS) was 20.5 (95% CI 13.1-28.1) months. In the 34 patients who
      then received capecitabine maintenance therapy, the median PFS was 8.1 (95% CI
      6.2-11.8) months and median OS was 23.1 (95% CI 17.8-28.5) months. A marked
      reduction in the vast majority of all grades of adverse event occurred on
      switching from initial XELOX to maintenance capecitabine chemotherapy including
      grades 1-2 (77 vs. 47%) and grade 3 (7 vs. 3%) neuropathy, diarrhoea and
      lethargy. CONCLUSIONS: Short-course XELOX followed by capecitabine maintenance
      therapy provides an active and well-tolerated treatment option for patients with
      previously untreated metastatic colorectal cancer. A median OS of more than 20
      months is promising and by limiting the number of oxaliplatin infusions, this
      approach minimises the risk of unwanted cumulative neurotoxicity, is cheaper and
      more convenient for both patients and healthcare providers.

PMID- 20676677
TI  - Optimization of two immunofluorescent antibodies for the detection of Escherichia
      coli using immunofluorescent microscopy and flow cytometry.
AB  - Two commercially available fluorescein isothiocyanate (FITC) -conjugated anti
      Escherichia coli antibodies, tested for immunofluorescence were assessed for
      their suitability in screening E. coli using flow cytometry. Staining efficacy
      was initially tested using immunofluorescent microscopy; and further optimization
      was carried out using flow cytometry. Initially, an acetone fixation step was
      utilized; however, it was determined statistically that the step could be omitted
      without impacting the assay and thus reduce the time involved. There was no
      statistical difference between the staining proficiency of the two antibodies
      employed. The percentage staining was quite low, approximately 10% for the two
      antibodies, which indicated that both were equally sensitive but ultimately, more
      specific antibodies are required for the detection of E. coli. Known proportions
      of target-E. coli (105, 106, and 107 cells/ml) were mixed with large quantities
      of non-target bacteria; there was a significant correlation among all the
      antibodies at the different bacterial cell concentrations. Therefore, despite the
      low staining percentage achieved on the bacterial cultures, there is a
      representative and comparative level of staining occurring, between samples and
      between bacterial strains.

PMID- 20676678
TI  - New cultural approaches for microaerophilic hyperthermophiles.
AB  - This article reports on a new culture system designed for studying the effects of
      nutritional factors on the growth of hyperthermophilic and chemolithotrophic
      microorganisms. The system comprises 5-l stainless steel jars, an automatic gas
      dispenser, propylene microplates, and a robotic platform. The culture system was
      validated using Aquifex aeolicus, a hyperthermophilic, chemolithotrophic, and
      microaerophilic bacterium, which requires hydrogen, oxygen, CO2, and minerals for
      growth. We demonstrated that the cell densities measured on 147 cultures of A.
      aeolicus microplated in jar at 80 degrees C under partial pressures (in kPa) of
      water vapor (47), H2 (117.7), O2 (28.1), CO2 (31.4), and N2 (3.9), followed a
      normal distribution, with a mean of 0.72 and a standard deviation of 0.04
      (variation coefficient: 5.7%). In addition, cross-comparison of the growth
      kinetics of A. aeolicus in serum bottles and in a jar system highlighted similar
      kinetics patterns (both mean growth rates were 0.18 and 0.17 h-1, respectively),
      whereas the maximum cell densities reached were slightly lower in jar than in
      bottle (0.73 vs. 0.88 OD units, respectively). Furthermore, these results showed
      that, contrary to bottles, the total pressure of gas in jars remained constant
      throughout the biotic experiments, even with seven microplates completely filled
      with grown cultures. In addition, this system has been validated also for
      hyperthermophilic strictly anaerobes such as Thermotoga maritima or aerobes such
      as Sulfolobus solfataricus. This new culture system offers an interesting
      alternative for cultivating hyperthermophiles, using gas as substrate under
      constant pressure, thus making it possible to miniaturize experiments and study a
      large number of nutritional factors in one experimental run.

PMID- 20676679
TI  - Autoantibody against hypoxia-inducible factor prolyl hydroxylase-3 is a potential
      serological marker for renal cell carcinoma.
AB  - PURPOSE: To verify the efficacy of a serum autoantibody against hypoxia-inducible
      factor prolyl hydroxylase-3 (PHD3) as a serological marker for RCC. METHODS:
      Serum samples and surgically resected tumor tissue specimens were obtained from
      22 patients with primary RCC, 15 of whom underwent radical nephrectomy and 7
      partial nephrectomy. Preoperative serum samples were obtained just before tumor
      resection. Postoperative serum samples were obtained from 17 patients at least 1
      month after tumor removal. Serum samples were also obtained from 26 healthy
      volunteers. Titers of the anti-PHD3 antibody (Ab) were determined by enzyme
      linked immunosorbent assay. RESULTS: Serum anti-PHD3 Ab titers were significantly
      higher in patients with RCC than in healthy volunteers (0.610 +/- 0.023 vs. 0.591
      +/- 0.031, P = 0.0001). Using a cutoff point of 0.599, sensitivity, specificity,
      and positivity for prediction of RCC were 86.4, 57.7, and 63.3%, respectively. In
      all 17 patients, titers of serum anti-PHD3 were decreased after the surgical
      resection compared with those before operation (0.622 +/- 0.023 vs. 0.580 +/-
      0.024, P = 0.0003). CONCLUSIONS: The present study suggests that the anti-PHD3 Ab
      may be a novel serological marker for RCC and the titer may reflect the tumor
      burden in each individual.

PMID- 20676680
TI  - t (11;18)(q21;q21) chromosome translocation (A1446-M1150) of MALT lymphoma in
      buccal mucosa.
AB  - PURPOSE: The t(11;18)(q21;q21) chromosome translocation is frequent in gastric
      MALT lymphoma, but the t(11;18)(q21;q21) chromosome translocation is very rare in
      other sites of MALT lymphomas. We investigated the possibility that MALT lymphoma
      occurred in the right buccal mucosa of a 66-year-old Japanese woman who had the
      t(11;18)(q21;q21) chromosome translocation. METHODS: Tumor specimens were
      examined by light microscopy and immunohistochemistry. To investigate where the
      present case has API-MALT1 fusion, we used the nested PCR and FISH analysis.
      RESULTS: Some colonized lymphoid follicles with mantle zone were observed on low
      power field, and centrocyte-like cells and monocytoid B cells were observed on
      high-power field. Immunohistochemical staining of the tumor was positive for bcl
      2, CD20, CD79a, CD43, Lambda, Kappa and was negative for CD10, IgG, IgG4, IgM,
      cyclin D1, bcl-6, CK (AE1/3), Helicobacter pylori. Using the nested PCR and FISH
      analysis, present case had the t(11;18)(q21;q21) chromosome translocation (A1446
      M1150). CONCLUSION: We report that MALT lymphoma in buccal mucosa has the
      t(11;18)(q21;q21) chromosome translocation (A1446-M1150) by using the nested PCR
      and FISH analysis. This is the first report of the t(11;18)(q21;q21) chromosome
      translocation (A1446-M1150) of MALT lymphoma in the oral cavity.

PMID- 20676681
TI  - Synergistic growth inhibition in HL-60 cells by the combination of acyclic
      retinoid and vitamin K2.
AB  - PURPOSE: The aim of this study was to assess the effects of acyclic retinoid
      (ACR) and vitamin K(2) (VK(2)) in HL-60 cells. METHODS: We used HL-60 cells, and
      the Trypan Blue dye exclusion method was used for cell proliferation assays. For
      detection of apoptosis, the Annexin V-binding capacity of treated cells was
      examined by flow cytometry. To evaluate the cell cycle, we used a FITC BrdU Flow
      KIT and flow cytometry. Total extracted and equivalent amounts of protein were
      examined by Western blotting using specific antibodies. RESULTS: ACR and VK(2)
      dose dependently inhibited the proliferation of HL-60 cells. These two agents in
      combination synergistically inhibited cell growth and induced apoptosis. VK(2)
      inhibited activation of the Ras/MAPK signaling pathway, and ACR plus VK(2)
      cooperatively inhibited phosphorylation of RXRalpha and the growth of HL-60
      cells. Moreover, ACR and VK(2) induced increases in G0/G1 phase HL-60 cells,
      alone and synergistically in combination. CONCLUSION: The synergistic effects of
      ACR and VK(2) on HL-60 cells may provide a novel strategy for treating leukemia.

PMID- 20676682
TI  - Development of larval thermotolerance and its impact on adult susceptibility to
      malathion insecticide and Plasmodium vivax infection in Anopheles stephensi.
AB  - The effect of the range of temperature on the thermal adaptation in Anopheles
      stephensi Liston 1901 was evaluated in the laboratory. Late third instar larvae
      of An. stephensi were exposed to variable temperatures viz. 37 degrees C, 39
      degrees C, 41 degrees C, 43 degrees C and 45 degrees C, and their lethal time to
      cause 50% mortality (LTM(50)) values were calculated. All larvae survived up to
      39 degrees C of exposure. However, at 45 degrees C, they died within 30 min of
      exposure. Pre-exposure to variable temperatures and re-exposure to higher
      temperatures conferred adaptive thermotolerance. The larvae pre-adapted at 41
      degrees C that were re-exposed to 43 degrees C, and larvae pre-adapted at 39
      degrees C that were re-exposed to 45 degrees C, were found more thermotolerant
      than the thermally non-adapted larvae. Adaptive cross-tolerance to malathion was
      also induced by pre-exposing them to 37 degrees C and 39 degrees C. It suggests
      that temperature stress also play an important role in the development of
      adaptive cross-tolerance to other stress conditions. Similarly, the oocyst rate
      was relatively more in adults that emerged from larvae pre-adapted at 40 degrees
      C as compared to adults that emerged from thermally non-adapted larvae and with
      lower oocyst load.

PMID- 20676683
TI  - Liver fluke beta-tubulin isotype 2 binds albendazole and is thus a probable
      target of this drug.
AB  - Albendazole is a benzimidazole drug which can be used to treat liver fluke
      (Fasciola hepatica) infections. Its mode of action is believed to be the
      inhibition of microtubule formation through binding to beta-tubulin. However, F.
      hepatica expresses at least six different isotypes of beta-tubulin, and this has
      confused, rather than clarified, understanding of the molecular mechanisms of
      benzimidazole drugs in this organism. Recombinant F. hepatica beta-tubulin
      proteins were expressed in, and purified from, Escherichia coli. These proteins
      were then used in pull-down assays in which albendazole was covalently linked to
      Sepharose. beta-Tubulin isotype 2 was pulled down in this assay, and this
      interaction could be reduced by adding competing albendazole. Molecular modelling
      of beta-tubulin isotypes suggests that changes in the side change conformations
      of residue 200 in the putative albendazole binding site may be important in
      determining whether, or not, a particular isotype will bind to the drug. These
      results, together with previous work demonstrating that albendazole causes
      disruption of microtubules in the liver fluke, strongly suggest that beta-tubulin
      isotype 2 is one of the targets of this drug.

PMID- 20676684
TI  - Cloning and characterization of a ribosomal protein L24 from Haemaphysalis
      longicornis eggs.
AB  - A fragment of ribosomal protein L24 was obtained from the complementary
      deoxyribonucleic acid (cDNA) library of Haemaphysalis longicornis eggs. The
      complete sequence of the clone was subsequently obtained using rapid
      amplification of the cDNA ends (RACE). Ribosomal protein L24 from H. longicornis
      had a high percentage similarity to this protein from different species.
      Conserved domains were also identified in RpL24. Real-time polymerase chain
      reaction (PCR) analysis showed that this gene is expressed in various tissues and
      different developmental stages of H. longicornis. Furthermore, HLL24 is mostly
      expressed in ovaries and salivary glands compared with other tissues in partially
      fed adult female ticks, and the expression level of HLL24 is significantly lower
      in eggs and larvas than in other developmental stages. RpL24 was also cloned from
      Haemaphysalis qinghaiensis and Hyalomma anatolicum anatolicum ticks,
      respectively. Comparison of their amino acid sequences revealed difference only
      in several amino acids. A vaccine based on the HLL24 recombinant protein could
      not protect rabbits against H. longicornis.

PMID- 20676685
TI  - Canine dirofilariosis caused by Dirofilaria immitis is a risk factor for the
      human population on the island of Gran Canaria, Canary Islands, Spain.
AB  - The aim of the present study was compare the prevalence of D. immitis in dogs and
      seroprevalence in humans of Gran Canaria (Canary Islands, Spain) taking into
      consideration the four isoclimatic areas of the island. A close relationship
      between the prevalence of Dirofilaria immitis in dogs and the seroprevalence in
      humans, in each isoclimatic area, was observed. The highest seroprevalence of
      infection in both canine and human hosts were found in a strip of mid-range
      altitude with 25.47% and 30.4% in dogs and 25.66% and 29.73% in humans,
      respectively. The coastal zone and the highest part of the island have
      prevalences significantly lower. These results demonstrate that the risk of
      infection by D. immitis in the human population in each area is tied to the
      prevalence in the canine population. Physicians should be alerted to the
      possibility of finding cases of human pulmonary dirofilariosis amongst the
      inhabitants of the island.

PMID- 20676686
TI  - Adhesion between plasma membrane and mitochondria with linking filaments in
      relation to migration of cytoplasmic droplet during epididymal maturation in
      guinea pig spermatozoa.
AB  - High-resolution microscopy has been used to investigate the mechanism of the
      migration of cytoplasmic droplets during epididymal maturation of guinea pig
      spermatozoa. On testicular spermatozoa, droplets are located at the neck and,
      after passage through the middle cauda epididymidis, migrate only as far as the
      center of the midpiece. Initially, the space between the plasma membrane and
      outer mitochondrial membranes outside the droplet is 30.8+/-11.0 nm, whereas on
      mature spermatozoa, it significantly (P<0.01) narrows to a more consistent 15.9+/
      1.3 nm. This is accompanied by the appearance of thin filaments cross-linking the
      two membranes above and below the droplet. Changes also occur in the arrangement
      of intramembranous particles (IMPs) in the plasma membrane overlying the
      midpiece. At the spermatid stage, linear arrays of IMPs are absent but appear on
      immature spermatozoa, where they are short with an irregular orientation, in the
      epididymis. On mature spermatozoa, numerous parallel linear arrays are present at
      the region where the plasma membrane adheres to the mitochondria. The membrane
      adhesion process can thus be observed two-dimensionally. The initial migration of
      the droplet from the neck is probably attributable to diffusion, with the
      formation of cross-linking filaments between the two membranes in the proximal
      midpiece preventing any backward flow and squeezing the droplet distally until it
      is arrested at the central midpiece by the filaments formed in the distal
      midpiece. The filaments might also stabilize the flagellum against hypo-osmotic
      stress encountered during ejaculation and within the female tract.

PMID- 20676687
TI  - Effects of Nissen fundoplication on endoscopic endoluminal radiofrequency
      ablation of Barrett's esophagus.
AB  - BACKGROUND: Endoscopic endoluminal radiofrequency ablation is achieving
      increasing acceptance as a mode of eliminating Barrett's metaplasia and, thus,
      reducing the risk of developing esophageal adenocarcinoma. It is believed that
      reducing exposure of the esophageal epithelium to acid is essential to achieve
      long-term ablation of Barrett's esophagus. However, it is unclear whether use of
      proton pump inhibitors or antireflux operations are more effective to accomplish
      this goal. METHODS: All patients who underwent endoscopic endoluminal
      radiofrequency ablation with the BARRx device (BARRx Medical, Sunnyvale, CA) were
      reviewed for date of initial ablation, length of Barrett's epithelium, presence
      or performance of Nissen fundoplication, all follow-up endoscopy and treatment,
      and posttreatment biopsy results. Patients were categorized by presence of Nissen
      fundoplication and presence of Barrett's metaplasia or dysplasia by biopsy at
      least 12 months following ablation and at last endoscopic follow-up. Data were
      analyzed by Fisher's exact test and Mann-Whitney U-test. RESULTS: Of 77 patients
      ablated, 47 had documented endoscopic follow-up at 12 months or longer following
      the ablation. Of these, 19 patients had Nissen fundoplication before, at the same
      time, or after ablation. Median length of Barrett's epithelium, with
      interquartile range (IQR), was 3 (2-12) cm in patients with fundoplication
      compared with 3 (2-7) cm without fundoplication (P = NS). Median follow-up was 15
      (12-24) months in fundoplication patients compared with 12.5 (12-17) months
      without (P = NS). One of 19 patients with fundoplication had persistent or
      recurrent Barrett's epithelium, compared with 7 of 28 without fundoplication (P =
      0.03). Of patients without fundoplication, those who had persistent or recurrent
      Barrett's had median Barrett's length of 10 cm (6-12 cm) compared with 3 cm (2-5
      cm) in patients who had ablated Barrett's (P = 0.03). Follow-up length was
      similar in those with ablated epithelium, 15 months (12-19 months), compared with
      those with persistent or recurrent Barrett's, 12 months (12-13 months) (P = NS).
      CONCLUSIONS: Patients who had fundoplication in conjunction with endoluminal
      radiofrequency ablation were more likely to achieve durable ablation compared
      with patients who were treated with proton pump inhibitor therapy. It appears
      that patients with long-segment Barrett's esophagus are at higher risk for
      persistent or recurrent Barrett's metaplasia. Consideration should be given for
      an antireflux operation in patients with long-segment Barrett's esophagus and
      planned endoluminal radiofrequency ablation.

PMID- 20676688
TI  - Combined pretherapeutic endoscopic and laparoscopic ultrasonography may predict
      survival of patients with upper gastrointestinal tract cancer.
AB  - BACKGROUND: The combination of endoscopic and laparoscopic ultrasonography (EUS
      LUS) is accurate for resectability assessment of patients with upper
      gastrointestinal cancer (UGIC). But neither the ability of EUS/LUS to predict
      long-term prognosis nor the potential impact on patient survival using this
      selection strategy has been investigated. This prospective, single-center study
      evaluated whether pretherapeutic EUS-LUS stratification related to the prognosis
      in UGIC patients and whether patient selection by this strategy provided a
      prognostic outcome comparable with survival data from the literature. METHODS:
      Each patient had a pretherapeutic tumor node metastasis (TNM) stage and a
      resectability assessment assigned based on EUS-LUS findings. Survival curves were
      constructed and compared for each of the EUS-LUS TNM stage and resectability
      groups at the end of the observation period. Finally, the R0 resection rate,
      median, and 5-year survival rates were compared with the literature. RESULTS:
      This study enrolled 936 consecutive patients with esophageal (n = 256), gastric
      (n = 273), or pancreatic (n = 407) cancer. A statistically significant survival
      difference (p < 0.01) between the different TNM stages and resectability groups
      predicted by EUS-LUS was observed regardless of the cancer type. The poor
      prognosis for the patients with irresectable or disseminated UGIC was accurately
      predicted by EUS and LUS. The R0 resection rate as well as the median and 5-year
      survival rates were comparable with data from the literature. CONCLUSION: The
      pretherapeutic EUS-LUS patient stratification related significantly to the final
      prognosis for UGIC patients. An EUS-LUS-based patient selection strategy seemed
      to provide a prognostic outcome similar to data from computed tomography (CT)
      based populations.

PMID- 20676689
TI  - Gastroesophageal reflux disease and esophageal motility in morbidly obese
      patients submitted to laparoscopic adjustable silicone gastric banding or
      laparoscopic vertical banded gastroplasty.
AB  - BACKGROUND: Laparoscopic adjustable silicone gastric banding (LASGB) and
      laparoscopic vertical banded gastroplasty (LVBG) are the most frequently
      performed restrictive operations for morbid obesity. The question of whether
      bariatric restrictive procedures increase or reduce gastroesophageal reflux
      disease (GERD) remains open. This study aimed to compare the long-term results of
      LASGB with those of LVBG in terms of postoperative GERD and esophageal motility
      function. METHODS: From February 1999 to December 2000, 175 patients underwent
      bariatric surgery. After 75 of these patients were excluded from the study, the
      remaining 100 patients were randomly assigned to one of two treatment groups:
      LASGB or LVBG. The end points of the study were evaluation of clinical and
      instrumental GERD and esophageal function. The follow-up protocol included
      clinical assessment using the Gastroesophageal Reflux Health-Related Quality-of
      Life (GERD-HRQOL) scale at 3, 12, and 96 months. Esophageal manometry, 24-h pH
      monitoring, and endoscopy were performed at 12 and 96 months. RESULTS: At 12
      months, GERD had developed in 13 (26%) LASGB and 11 (21.6%) LVBG patients. In the
      majority of cases, GERD resulted from pouch dilation or poor compliance and
      required either reoperation (ten after LASGB and three after LVBG) or endoscopic
      dilation of the neopylorus (four after LVBG). In all, 71 patients completed the
      96-month follow-up protocol. The findings showed that three (11.5%) of 26 LASGB
      patients and four (9%) of 45 LVBG patients were receiving proton pump inhibitor
      (PPI) therapy for GERD. Postoperative lower esophageal sphincter (LES) pressure
      and esophageal motility did not differ from preoperative data except for the
      presence of aperistaltic waves in one LASGB and two LVBG symptomatic GERD
      patients. CONCLUSIONS: No significant association between gastric restrictive
      procedures and GERD or esophageal function was found during long-term follow-up
      assessment. The increased occurrence of GERD in the early follow-up period often
      is due to a technical defect or poor patient compliance.

PMID- 20676691
TI  - "Virtual Pediatric Renal Grand Rounds": an innovative e-learning.

PMID- 20676692
TI  - Trabecular bone volume and osteoprotegerin expression in uremic rats given high
      calcium.
AB  - Calcium (Ca)-containing phosphate binders have been recommended for the treatment
      of hyperphosphatemia in children with chronic kidney disease. To study the
      effects of high Ca levels on trabecular bone volume (BV) and osteoprotegerin
      (OPG) expression in uremic young rats, a model of marked overcorrection of
      secondary hyperparathyroidism was created by providing a diet of high Ca to 5/6
      nephrectomized young rats (Nx-Ca) for 4 weeks. The results of chondrocyte
      proliferation and apoptosis, osteoclastic activity, OPG expression and BV were
      compared among intact rats given the control diet, intact rats given a high Ca
      diet and 5/6 nephrectomized rats given the control diet (Nx-Control) and the high
      Ca diet (Nx-Ca). Ionized Ca levels were higher and parathyroid hormone levels
      were lower in Nx-Ca rats than in the other groups. Final weight, final length and
      final tibial length of Nx-Ca rats were significantly less than those of the other
      groups, although the length gain did not differ among the groups. The
      hypertrophic zone width was markedly enlarged in Nx-Ca rats. Chondrocyte
      proliferation rates did not differ among the groups, whereas osteoclastic
      activity was decreased in Nx-Ca rats compared with the Nx-Control animals. The
      OPG expression and BV were increased in Nx-Ca rats compared with the Nx-Control
      rats. Increased BV should improve bone strength, whereas disturbance of
      osteoclastogenesis interferes with bone remodeling. Bone quality has yet to be
      determined in high Ca-fed uremic young rats.

PMID- 20676693
TI  - PPARgamma and chronic kidney disease.
AB  - Peroxisome proliferator-activated receptor-gamma (PPARgamma) agonists,
      exemplified by the thiazolidinediones (TZDs), have been used extensively for
      their beneficial effects to improve insulin sensitivity and lipid metabolism in
      type 2 diabetic patients. PPARgamma receptors are part of the steroid hormone
      nuclear receptor family and, when activated by agonist binding, can affect
      numerous target genes expressing PPAR response elements. Results from
      experimental studies and a limited number of studies in humans suggest that
      PPARgamma agonists have manifold effects beyond those on dysmetabolic syndrome.
      These potentially beneficial actions are mediated via renal parenchymal and
      infiltrating cells and modulate fibrotic, inflammatory, immune, proliferative,
      reactive oxygen and mitochondrial injury pathways. Thus, the potential benefits
      of TZDs in chronic kidney disease impact numerous pathogenic pathways. This
      review will focus on evidence of the effects of TZDs in nondiabetic chronic
      kidney disease in experimental and human disease settings.

PMID- 20676694
TI  - Cardiorespiratory fitness is a marker of cardiovascular health in renal
      transplanted children.
AB  - Children with renal transplants (TX) are at increased risk of cardiovascular (CV)
      disease. Study objectives were to assess the level of cardiorespiratory fitness
      (CR fitness) and daily physical activity (PA) in renal TX children and
      adolescents in relation to traditional cardiovascular risk factors. Laboratory
      testing included assessment of CR fitness by treadmill exercise testing
      (VO(2peak)), 24-h ambulatory blood-pressure (ABPM) measurement, oral glucose
      tolerance test (OGTT), anthropometrics and measurement of lipid levels. PA was
      self-reported by questionnaire. Twenty-two TX patients with a median (range) age
      14.5 (9-18) years were tested. Median V0(2peak) was 66% (36-97) of the expected
      values compared with controls. Nineteen (86%) children reported <60 min of daily
      moderate to vigorous physical activity (MVPA). Sixteen (73%) were hypertensive
      and 8 (34%) were overweight or obese. Four children fulfilled the criteria for a
      metabolic syndrome. Children with at least 2 of the 3 metabolic risk factors
      (hypertension, overweight, and glucose intolerance, n=7) achieved significantly
      lower VO(2peak) compared with those with one or none of these factors (median
      V0(2peak) 45% and 73% of the expected values respectively, p=0.003). Renal TX
      children and adolescents have severely impaired CR fitness and PA. Reduced CR
      fitness was associated with the clustering of CV risk factors. Routine counseling
      for increased PA is strongly recommended.

PMID- 20676695
TI  - Social support and depressive mood 1 year after diagnosis of breast cancer
      compared with the general female population: a prospective cohort study.
AB  - BACKGROUND: Social support may influence the impact of stressful life events on
      breast cancer patients' psychological state. However, the precise status of
      depressive mood in breast cancer during the first year after diagnosis is not yet
      known. METHODS: Perceived social support, health-related quality of life, and
      depressive mood were assessed at enrollment and 1 year after breast cancer
      diagnosis in 286 women newly diagnosed with stages I-III breast cancer. Breast
      cancer patients' social support and depressive mood at diagnosis and 1 year after
      diagnosis were compared with the general female population (GFP), and predictors
      of worsened depressive mood were identified. RESULTS: All subscales of social
      support and depressive mood among breast cancer patients were significantly lower
      at one after diagnosis than at diagnosis (all p<0.001). At diagnosis, breast
      cancer patients reported better emotional (p=0.004), informational (p=0.006), and
      affectionate support (p=0.002), and poorer depressive mood (p<0.001) than the
      GFP. After 1 year, however, perceived social support in breast cancer patients
      was significantly decreased and depressive mood was significantly improved,
      becoming similar to scores of the GFP. Only tangible support was significantly
      lower than the GFP at 1 year after diagnosis (p=0.028). Hierarchical multiple
      logistic regression analysis for best fitting the model statistically and
      clinically indicated that decreased emotional support, transition to post
      menopausal status, impaired role functioning, and financial difficulties
      predicted deteriorated depressive mood. CONCLUSION: Breast cancer patients might
      have greater control over tangible support than any other type of social support.
      Together with the transition to post-menopausal status, decreased perceived
      emotional social support was the best predictor of depressive mood among breast
      cancer patients during the first year after diagnosis.

PMID- 20676696
TI  - Primary care for young adult cancer survivors: an international perspective.
AB  - PURPOSE: Internationally, family physicians (FP) are not routinely involved in
      young adult cancer (YAC) care. In this short report, we would like to make a
      compelling argument for primary care involvement. METHODS: Comparative
      descriptions and literature review. RESULTS: Cancer among YAs is rare and usually
      not the first thing that comes into the FP's mind. Youth is sometimes mistakenly
      regarded as a protective factor. Across the countries, almost all YACs are
      treated in tertiary health care facilities with specialists providing the
      majority of care. Health care services are covered by the universal health
      insurance in Denmark, The Netherlands, and Canada but not in the US. Once the YAC
      has completed acute treatment and follow-up care, they often return to the care
      of the FPs who may potentially be expected to deal with and take action upon any
      possible medical, mental health, and psychosocial issues the YA cancer patient
      may present with. The role of the FP in follow-up care seems to be very limited.
      CONCLUSIONS: YACs in the western world seem to have comparable medical and
      psychosocial problems. However, the nature of health insurance is such that it
      impacts differently on the care of this group of cancer patients. Primary care
      features such as patient-centered, integrated, and comprehensive care over
      extended periods of time bring the FP into the unique position to provide follow
      up for YAC. However, this will require integrating patient's perspectives on
      their care, professional continuing medical education (CME) initiatives, and an
      enhanced cooperative effort between those delivering and coordinating cancer
      care.

PMID- 20676697
TI  - Minimally invasive (laparoscopic and robot-assisted) approach for solid
      pseudopapillary tumor of the distal pancreas: a single-center experience.
AB  - BACKGROUND/PURPOSE: A single-institutional experiences of solid pseudopapillary
      tumor (SPT) in the distal pancreas were retrospectively reviewed with special
      reference to a minimally invasive approach. METHODS: Thirty-five patients with
      SPT of the distal pancreas treated during the past 20 years were retrospectively
      evaluated. We divided the patients into 2 groups based on the surgical approach:
      the laparoscopic/robot-assisted surgery (LR) group and the conventional open
      surgery (O) group. We reviewed the chronological changes and characteristics of
      SPT. A comparative analysis of the two groups (LR vs. O) was conducted in terms
      of perioperative surgical outcomes. RESULTS: The discovery of relatively small
      SPTs without symptoms seemed to be increasing (p < 0.05). Eleven of the 35
      patients were assigned to the LR group. Ten patients were female and 1 was male,
      and they had a median age of 32 years (range 24-62 years) and a median tumor size
      of 3.6 cm (range 1-8.5 cm). Eight patients underwent laparoscopic distal
      pancreatectomy with or without splenectomy, and the remaining 3 underwent robot
      assisted central pancreatectomy with pancreaticogastrostomy. In the comparative
      analysis of the LR and O groups, smaller tumor size, earlier oral intake, and
      shorter hospital stay, without increasing morbidity, were noted in the LR group
      (p < 0.05). CONCLUSIONS: A minimally invasive (laparoscopic/robot-assisted)
      approach for SPT of the distal pancreas is thought to be more appropriate than
      and preferable to conventional open surgery in well-selected patients.

PMID- 20676698
TI  - Endoscopic management of laparoscopic cholecystectomy-associated bile duct
      injuries.
AB  - BACKGROUND/PURPOSE: The efficacy of the endoscopic management of laparoscopic
      cholecystectomy (LC)-associated bile duct injuries is unclear because few studies
      on the issue report methods matched to injury type or long-term follow-up data.
      METHODS: Records from our institution's 11-year experience with the endoscopic
      management of LC-associated bile duct injuries were reviewed. Leakage was managed
      with a 5- to 7F endoscopic nasobiliary drainage (ENBD) tube for 1 week without
      endoscopic sphincterotomy (EST). Stricture was managed with the placement of a
      single 7F plastic stent for 1-2 months without EST. RESULTS: Fifteen cases were
      experienced. Of the 11 cases (77.8%) of leakage, 7 improved clinically and on
      imaging after ENBD, 2 did not resolve until after the placement of a single
      plastic 7F stent for several more days, and 2 others with leakage and high risk
      for accidental ENBD removal improved after the placement of a single 7F stent.
      All 4 cases of stricture resolved completely after the placement of a single 7F
      stent. There were no severe complications of the endoscopic procedure. At long
      term follow-up, no patient had recurrence of symptoms or complications on
      imaging. CONCLUSIONS: ENBD for leakage and biliary stenting for strictures are
      safe and effective treatments for these LC-associated injuries.

PMID- 20676699
TI  - Risk factors for postoperative infectious complications after hepatectomy.
AB  - BACKGROUND/PURPOSE: This study aimed to clarify the incidence of surgical site
      infections (SSIs) after hepatectomy. METHODS: The database records of three
      hundred and eight patients who underwent elective surgical treatment for
      hepatolithiasis, hepatocellular carcinoma (HCC), and metastatic carcinoma were
      retrospectively analyzed to determine the occurrence of postoperative infectious
      complications. The incidences of SSIs, classified as superficial or deep
      incisional SSIs and organ or space SSIs, and all other infectious complications
      within 30 days after hepatectomy were evaluated. RESULTS: The incidences of SSIs
      after a hepatectomy for hepatolithiasis (23.8%) were higher than those after a
      hepatectomy for HCC (11.3%) (p = 0.034) and after a hepatectomy for metastatic
      carcinoma (2.7%) (p < 0.001), and the incidence of SSIs after a hepatectomy for
      HCC was higher than that after a hepatectomy for metastatic carcinoma (p =
      0.028). However, there was no significant difference in the incidence of remote
      site infections between the three groups. The incidence of superficial or deep
      incisional SSIs after a hepatectomy for hepatolithiasis (11.9%) was higher than
      that after a hepatectomy for metastatic carcinoma (1.4%) (p < 0.001) and the
      incidence of superficial or deep incisional SSIs after a hepatectomy for HCC
      (7.8%) was higher than that after a hepatectomy for metastatic carcinoma (1.4%)
      (p = 0.050). There was a significant difference in the incidence of space/organ
      SSIs between the patients with hepatolithiasis (11.9%) and HCC patients (3.6%) (p
      = 0.029), and between the patients with hepatolithiasis and metastatic carcinoma
      patients (1.4%) (p < 0.001). The rate of positive bile culture was 36.2% in all
      patients in this study, and the rates were 83.3, 7.8, and 10.0% for patients with
      hepatolithiasis, HCC, and metastatic carcinoma, respectively. A significantly
      higher (p < 0.001) positive bile culture rate was observed in patients with
      hepatolithiasis as compared with HCC or metastatic carcinoma patients.
      CONCLUSIONS: Our study suggests the existence of a relationship between
      postoperative SSIs and bile infection, thus supporting the proposed relationship
      between post-hepatectomy infection and such variables as liver function, blood
      sugar control, and nutritional status.

PMID- 20676700
TI  - Prediction and management of a low-lying costal arch which restricts the
      operative working space during laparoscopic cholecystectomy.
AB  - BACKGROUND/PURPOSE: Laparoscopic cholecystectomy is difficult to perform in
      patients with a low-lying costal arch that entirely covers the liver. We
      conducted this study to clarify the factors related to a low-lying costal arch
      and establish countermeasures to circumvent this characteristic. METHODS: The
      study included 103 consecutive patients who underwent a laparoscopic
      cholecystectomy. The possible clinical factors associated with a low-lying costal
      arch restricting the operative working space were analyzed. The position of the
      liver against the costal arch and the presumed surgical visual angle for
      laparoscopic cholecystectomy, comprising the hepatic porta, umbilicus, and costal
      arch, were estimated with abdominal multidetector computed tomography (MDCT).
      RESULTS: Seven (7%) patients had a low-lying costal arch presenting an inadequate
      exposure of Calot's triangle and restricted instrument mobility during
      laparoscopic cholecystectomy, and three patients required conversion to a
      laparotomy. A low-lying costal arch was significantly associated with advanced
      age, shorter stature, lighter body weight, coexisting kyphoscoliosis, gallbladder
      pathology, laparotomy conversion, and most of all, the liver edge lying above the
      costal arch and a narrow surgical visual angle upon MDCT. Of the seven patients
      with a critical low-lying costal arch, four underwent a successful laparoscopic
      cholecystectomy, this being done by lifting the right costal arch to create a
      workable surgical field; the rib-lifting procedure was planned as part of the
      scheduled procedure in the other three patients because the preoperative MDCT
      examination indicated a poor working space for a laparoscopic cholecystectomy.
      CONCLUSIONS: A low-lying costal arch is a substantial risk factor for conversion
      to a laparotomy when performing a laparoscopic cholecystectomy. However, the
      operative difficulty related to a low-lying costal arch can be predicted by using
      preoperative MDCT images and can be managed with proper planning and the
      appropriate use of the rib-lifting technique.

PMID- 20676701
TI  - Single stage anterior reconstruction using titanium mesh cages in neglected
      kyphotic tuberculous spondylodiscitis of the cervical spine.
AB  - Cervical tuberculous spondylodiscitis is a serious, hazardous disorder and to our
      knowledge, hardly any reports focused on the use of titanium mesh cages in its
      treatment. The aim of this work is to evaluate the efficacy of using a titanium
      mesh cage compared to iliac crest grafting regarding correction of the deformity,
      fusion rate and to report the incidence of complications. A prospective, non
      randomized multicentre study of 30 patients with cervical tuberculous
      spondylodiscitis presenting with a neglected kyphotic deformity. The average age
      was 44.5 years; 18 had neurological deficits. All patients had a single stage
      radical debridement, decompression, and instrumentation. The anterior column was
      reconstructed with a titanium mesh cage in 16 patients (Group 1) and an
      autogenous iliac bone strut graft in 14 (Group 2). Both groups were followed for
      a minimum of 2 years. Group 1 showed a better sagittal profile and local kyphosis
      was corrected from an average of 36 degrees  (10 degrees -62 degrees ) to an
      average of -6 degrees  (+4 degrees  to -16 degrees ) compared to Group 2
      corrected from an average of 30 degrees  (6 degrees -48 degrees ) to an average
      of -1 degrees  (+2 degrees  to -13 degrees ). Group 1 patients showed a solid
      bony fusion without any recurrence of infection while Group 2 showed a higher
      incidence of nonunion and of persistent donor site morbidity. The use of titanium
      mesh cages effectively restores the sagittal profile while adding immediate
      stability. There is no donor site morbidity, recurrence, or persistence of
      infection associated with their implantation.

PMID- 20676702
TI  - Primary carcinoid tumor of the filum terminale--a case report.
AB  - Carcinoid tumors with a primary site in the central nervous system have not been
      reported in literature yet. We report here about a 41-year-old patient with
      recurrent and progressive low back pain and bilateral S1 radiculopathy on
      admission. The patient underwent hemi-laminectomies of the vertebral bodies L5
      and S1 and an en bloc resection of the tumor. Postoperative histopathological
      examination resulted in a well-differentiated intrathecal neuroendocrine tumor
      (carcinoid) of the terminal filum. Postoperative staging showed no pathological
      abnormalities and no tumor recurrence after 6 months. Even though rare,
      carcinoids should be considered as differential diagnosis of tumors occurring in
      the CNS.

PMID- 20676703
TI  - Preserved cognition after deep brain stimulation (DBS) in the subthalamic area
      for Parkinson's disease: a case report.
AB  - At present, subthalamic nucleus (STN) stimulation is the preferred procedure for
      the amelioration of motor symptoms in medication refractory Parkinson's disease.
      Results are however impaired by negative impacts on mood, cognition, incentive,
      and social judgment. Alternative targets are therefore explored. We describe a
      case with stimulation of subthalamic fibre tracts that showed clear improvement
      of cognitive and social abilities. Avoiding the STN may be advantageous in
      progressive Parkinson's disease to avoid non-motor complications and enhance
      quality of life.

PMID- 20676704
TI  - The ultrastructure of the extrusomes in Pseudourostyla cristata, a hypotrichous
      ciliated protozoan.
AB  - By using scanning and transmission electron microscopy, the present study
      demonstrates a great number of trichocyst-like extrusomes distributed in the
      cortical cytoplasm of the protozoan Pseudourostyla cristata, a hypotrichous
      ciliate. Of these, the mature organelles are rod-shaped with a cap consisting of
      tubular structures, a tip located at the apex of the cap, a body consisting of
      strateform structures of uneven electron density and an elongated shaft located
      along the longitudinal central axis of the body. The electron microscopic
      observations suggest that the extrusive organelles in P. cristata might undergo a
      morphogenetic process including the following sequential events: the occurrence
      of the vesicles in the cytoplasm, the condensation of the fibrous substances
      within the vesicles, the appearance of the electron-dense shaft, and the
      formation of the cap. In contrast with a large quantity of extrusomes in
      trophozoit P. cristata, there are no such extrusive organelles in the encysted
      cells of the ciliate. The phenomena that P. cristata ciliates can readily enter
      physiological reorganization or encysting phases and discharge a great number of
      their extrusomes when prepared for SEM and TEM observation suggest that the
      extrusive process of the extrusomes in P. cristata might have an important
      influence on the life activity of the ciliate and could be one of the causes
      leading to the physiological reorganization and the encysting of the ciliate.
      These reactions of P. cristata might be a protective or defensive response to the
      environmental changes.

PMID- 20676705
TI  - Generation of transgenic mice for conditional overexpression of Sox9.
AB  - Sox9 belongs to the family of Sry-related high-mobility group box transcription
      factors controlling cell fate, cell proliferation and differentiation in various
      tissues, including cartilage, testis, the central nervous system, kidney, and
      gastrointestine. Mice conditionally lacking Sox9 have revealed essential roles
      for Sox9 in these tissues. To gain further insight into the role of Sox9 in
      different tissues and at different stages of development, we have generated a
      transgenic mouse line to express Sox9 in a Cre recombinase-dependent manner. The
      construct contained the human cytomegalovirus enhancer and chicken beta-actin
      promoter, and a floxed monomeric red fluorescence protein 1 (mRFP1) cassette to
      direct ubiquitous expression of mRFP1. Cre expression removed the mRFP1 gene,
      allowing expression of Sox9 and enhanced green fluorescent protein. Expectedly,
      overexpression of Sox9 in chondrocytes using Col2a1-Cre mice suppressed
      chondrocyte hypertrophy, and delayed terminal differentiation and subsequent
      ossification. Misexpression of Sox9 in hypertrophic chondrocytes using Col10a1
      Cre knock-in mice also delayed terminal differentiation. This Sox9 conditional
      transgenic mouse line will be a valuable tool to uncover tissue-specific and
      developmental stage-specific functions of Sox9.

PMID- 20676707
TI  - DFT modeling on the suitable crown ether architecture for complexation with Cs+
      and Sr2+ metal ions.
AB  - Crown ether architectures were explored for the inclusion of Cs(+) and Sr(2+)
      ions within nano-cavity of macrocyclic crown ethers using density functional
      theory (DFT) modeling. The modeling was undertaken to gain insight into the
      mechanism of the complexation of Cs(+) and Sr(2+) ion with this ligand
      experimentally. The selectivity of Cs(+) and Sr(2+) ions for a particular size of
      crown ether has been explained based on the fitting and binding interaction of
      the guest ions in the narrow cavity of crown ethers. Although, Di-Benzo-18-Crown
      6 (DB18C6) and Di-Benzo-21-Crown-7 (DB21C7) provide suitable host architecture
      for Sr(2+) and Cs(+) ions respectively as the ion size match with the cavity of
      the host, but consideration of binding interaction along with the cavity matching
      both DB18C6 and DB21C7 prefers Sr(2+) ion. The calculated values of binding
      enthalpy of Cs metal ion with the crown ethers were found to be in good agreement
      with the experimental results. The gas phase binding enthalpy for Sr(2+) ion with
      crown ether was higher than Cs metal ion. The ion exchange reaction between Sr
      and Cs always favors the selection of Sr metal ion both in the gas and in micro
      solvated systems. The gas phase selectivity remains unchanged in micro-solvated
      phase. We have demonstrated the effect of micro-solvation on the binding
      interaction between the metal ions (Cs(+) and Sr(2+)) and the macrocyclic crown
      ethers by considering micro-solvated metal ions up to eight water molecules
      directly attached to the metal ion and also by considering two water molecules
      attached to metal-ion-crown ether complexes. A metal ion exchange reaction
      involving the replacement of strontium ion in metal ion-crown ether complexes
      with cesium ion contained within a metal ion-water cluster serves as the basis
      for modeling binding preferences in solution. The calculated O-H stretching
      frequency of H(2)O molecule in micro-solvated metal ion-crown complexes is more
      red-shifted in comparison to hydrated metal ions. The calculated IR spectra can
      be compared with an experimental spectrum to determine the presence of micro
      solvated metal ion-crown ether complexes in extractant phase.

PMID- 20676708
TI  - Reactivity versus steric effects in fluorinated ketones as esterase inhibitors: a
      quantum mechanical and molecular dynamics study.
AB  - Carboxylesterases (CEs) are a family of ubiquitous enzymes with broad substrate
      specificity, and their inhibition may have important implications in
      pharmaceutical and agrochemical fields. One of the most potent inhibitors both
      for mammalian and insect CEs are trifluoromethyl ketones (TFMKs), but the
      mechanism of action of these chemicals is not completely understood. This study
      examines the balance between reactivity versus steric effects in modulating the
      activity against human carboxylesterase 1. The intrinsic reactivity of the ketone
      moiety is determined from quantum mechanical computations, which combine gas
      phase B3LYP calculations with hydration free energies estimated with the IEF/MST
      model. In addition, docking and molecular dynamics simulations are used to
      explore the binding mode of the inhibitors along the deep gorge that delineates
      the binding site. The results point out that the activity largely depends on the
      nature of the fluorinated ketone, since the activity is modulated by the balance
      between the intrinsic electrophilicity of the carbonyl carbon atom and the ratio
      between keto and hydrate forms. However, the results also suggest that the
      correct alignment of the alkyl chain in the binding site can exert a large
      influence on the inhibitory activity, as this effect seems to override the
      intrinsic reactivity features of the fluorinated ketone. Overall, the results
      sustain a subtle balance between reactivity and steric effects in modulating the
      inhibitory activity of TFMK inhibitors.

PMID- 20676710
TI  - An unusual case of inguinal hernia with spontaneous evisceration.
AB  - Spontaneous evisceration is a very rare and potentially fatal complication of
      abdominal wall hernia. It has been commonly reported in the case of umbilical
      hernia in patients with chronic liver disease with tense ascites. With other
      hernias, such as incisional hernia and inguinal hernia, the complication has been
      reported only once. Here we present a case report of spontaneous evisceration in
      an inguinal hernia in a patient with comorbid chronic obstructive airway disease.
      Management of the condition using prosthetic mesh repair risks mesh infection,
      while the use of non-prosthetic repair risks recurrence of the hernia due to the
      absence of stout natural tissues. Use of a biological mesh for the condition
      seems quite plausible. Thorough saline washes of the eviscerated organ, excision
      of redundant/unhealthy skin and strict adherence to the fundamental principles of
      hernia repair is desired in managing the condition.

PMID- 20676709
TI  - Study of interactions between Mycobacterium tuberculosis proteins: SigK and anti
      SigK.
AB  - The development of novel antituberculosis therapeutic molecules is a global
      health concern. Complex gene expression in Mycobacterium tuberculosis is mediated
      mainly by various sigma factors. The SigK protein binds to RNA polymerase,
      facilitating the expression of genes encoding the antigenic proteins mpt70 and
      mpt83. The anti-SigK protein is a negative regulator of SigK and inhibits the
      initiation of transcription. This study focuses on the interactions between SigK
      and the N-terminal domain of anti-SigK. The 3D structures of SigK (187 residues)
      and the N-terminal domain of anti-SigK (92 residues) are elucidated, using the
      crystal structures of the A and B chains of sigma E and anti-sigma ChrR of
      Rhodobacter spheroides (PDB code: 2Q1Z) as templates, respectively. Molecular
      dynamic simulations were performed for the SigK and anti-SigK proteins to refine
      their structures. The predicted active sites of SigK and anti-SigK and the
      results of protein-protein docking studies revealed the residues that are
      important for binding. The models generated and the binding site residues
      identified in this work throw new light on the interactions between the sigma K
      and anti-sigma K proteins, which should further aid the modulation of antigenic
      protein production in Mycobacterium tuberculosis.

PMID- 20676711
TI  - Open tension-free Lichtenstein repair of inguinal hernia: use of fibrin glue
      versus sutures for mesh fixation.
AB  - PURPOSE: To investigate pain and other complications following inguinal
      hernioplasty performed by the Lichtenstein technique with mesh fixation by fibrin
      glue or sutures. METHODS: Five hundred and twenty patients were enrolled in this
      12-month observational multicenter study and received either sutures or fibrin
      glue (Tissucol((r))/Tisseel((r))) based on the preference of the surgeon. Pain,
      numbness, discomfort, recurrence, and other complications were assessed
      postoperatively and at 1, 3, 6, and 12 months. Pain intensity was assessed by a
      visual analog scale (VAS; 0 [no pain] to 10 [worst pain]). RESULTS: One hundred
      and seventy-one patients received sutures and 349 received fibrin glue. During
      the early postoperative phase, 87.4% of patients in the fibrin glue group and
      76.6% of patients in the sutures group were complication-free (P = 0.001).
      Patients who received fibrin glue were also less likely to experience
      hematoma/ecchymosis than those in the suture group (both P = 0.001). The mean
      pain score was significantly lower in the fibrin group than the sutures group
      (2.5 vs. 3.2, P < 0.001). At 1 month, significantly fewer patients in the fibrin
      glue group reported pain, numbness, and discomfort compared with patients in the
      sutures group (all P < 0.05). Fibrin glue patients also experienced less intense
      pain (0.6 vs. 1.2; P = 0.001). By 3 months, the between-group differences had
      disappeared, except for numbness, which was more prevalent in the sutures group.
      By 12 months, very few patients reported complications. CONCLUSIONS: Tissucol
      fibrin glue for mesh fixation in the Lichtenstein repair of inguinal hernia shows
      advantages over sutures, including lower incidence of complications such as pain,
      numbness, and discomfort, and should be considered as a first-line option for
      mesh fixation in hernioplasty.

PMID- 20676712
TI  - Educational level and osteoporosis risk in postmenopausal Moroccan women: a
      classification tree analysis.
AB  - The objectives of this study are (1) to evaluate whether the prevalence of
      osteoporosis and peripheral fractures might be influenced by the educational
      level and (2) to develop a simple algorithm using a tree-based approach with
      education level and other easily collected clinical data that allow clinicians to
      classify women into varying levels of osteoporosis risk. A total number of 356
      women with a mean age of 58.9+/-7.7 years were included in this study. Patients
      were separated into four groups according to school educational level; group 1,
      no education (n=98 patients); group 2, elementary level (n=57 patients); group 3,
      secondary level (n=138 patients) and group 4, university level (n=66 patients).
      We observed dose-response linear relations between educational level and mean
      bone mineral density (BMD). The mean BMDs of education group 1 (10.39% (lumbar
      spine), 10.8% (trochanter), 16.8% (wrist), and 8.8% (femoral neck)) were lower
      compared with those of group IV (p<0.05). Twelve percent of patient had
      peripheral fractures. The prevalence of peripheral fractures increased with
      lowered educational levels. Logistic regression analysis revealed a significant
      independent increase in the risk of peripheral fracture in patients with no
      formal education (odds ratio, 5.68; 95% , 1.16-27.64) after adjustment for age,
      BMI and spine BMD. Using the classification tree, four predictors were identified
      as the most important determinant for osteoporosis risk: the level of education,
      physical activity, age>62 years and BMI<30 kg/m2. This algorithm correctly
      classified 74% of the women with osteoporosis. Based on the area under the
      receiver-operator characteristic curves, the accuracy of the Classification and
      Regression Tree (CART) model was 0.79. Our findings suggested that a lower level
      of education was associated with significantly lower BMDs at the lumbar spine and
      the hip sites, and with higher prevalence of osteoporosis at these sites in a
      dose-response manner, even after controlling for the strong confounders. On the
      other hand, our CART algorithm based on four clinical variables may help to
      estimate the risk of osteoporosis in a health care system with limited resources.

PMID- 20676713
TI  - Characterisation of invasive group B streptococci from adults in Denmark 1999 to
      2004.
AB  - The aim of this study was to characterise the group B streptococci (GBS) isolates
      causing severe invasive infections in patients >15 years of age in Denmark from
      1999 to 2004. A total of 411 invasive GBS isolates were phenotypically
      characterised by the capsular polysaccharide (CPS) serotype and protein Calpha,
      Cbeta and R4. The incidence of invasive GBS disease ranged from 2.2 to 3.2 per
      100,000 adults in the study period, being highest among adults over 65 years of
      age. Diabetes was observed in 15% of the cases, 12% had alcohol abuse and 7% had
      cancer. Of all isolates, 77% were CPS serotypes Ia, Ib, III or V. The surface
      proteins Calpha or R4 were detected as the only protein in 57% of the GBS
      isolates. Cbeta was detected in 12% of the isolates, but always in combination
      with either Calpha or both Calpha and R4. The incidence of invasive GBS
      infections continued to increase in Denmark from 1999 to 2004. In that period,
      the overall case fatality was 14%. The most prevalent CPS serotypes were
      serotypes III, Ia, V and Ib. The most prevalent surface protein was R4 when
      testing for R4, Calpha and Cbeta. There was no clear relation between the GBS
      phenotype and infections with fatal outcome.

PMID- 20676714
TI  - Inducing chromosome pairing through premature condensation: analysis of wheat
      interspecific hybrids.
AB  - At the onset of meiosis, chromosomes first decondense and then condense as the
      process of recognition and intimate pairing occurs between homologous
      chromosomes. We show here that okadaic acid, a drug known to induce chromosome
      condensation, can be introduced into wheat interspecific hybrids prior to meiosis
      to induce chromosome pairing. This pairing occurs in the presence of the Ph1
      locus, which usually suppresses pairing of related chromosomes and which we show
      here delays condensation. Thus the timing of chromosome condensation during the
      onset of meiosis is an important factor in controlling chromosome pairing.

PMID- 20676716
TI  - Primary intracranial leiomyosarcoma in an HIV-infected patient.
AB  - Primary intracranial leiomyosarcomas are rare tumors arising from the mesenchymal
      cells of the dura matter or the cerebral blood vessels. Only 14 cases of primary
      intracranial leiomyosarcoma are reported in the literature. We report a case of
      primary intracranial leiomyosarcoma in an human immunodeficiency virus-positive
      patient with a CD4 count of 14 cells/MUL. Additionally, in-situ hybridization of
      Epstein-Barr virus (EBV) early RNA stained sections highlighted the tumor cells,
      consistent with the presence of EBV. Review of the literature strongly suggests
      an association between AIDS, EBV, and primary intracranial leiomyosarcoma. Given
      the paucity of information in the literature, we review possible chemotherapeutic
      agents for treatment of primary intracranial leiomyosarcoma in patients
      refractory to surgical resection and radiation therapy.

PMID- 20676715
TI  - Regulation of barley miRNAs upon dehydration stress correlated with target gene
      expression.
AB  - We aim to identify conserved and dehydration responsive microRNAs (miRNAs) in
      Hordeum vulgare (barley). A total of 28 new barley miRNAs belonging to 18
      distinct miRNA families were identified. Detailed nucleotide analyses revealed
      that barley pre-miRNAs are in the range of 46-114 nucleotides with average of
      77.14. Using 28 newly detected miRNAs as queries, 445 potential target mRNAs were
      predicted. The predicted miRNAs were differentially expressed and some of them
      behaved similarly in leaf and root tissues upon stress treatment. Hvu-MIR156, Hvu
      MIR166, Hvu-MIR171, and Hvu-MIR408 were detected as dehydration stress-responsive
      barley miRNAs. To discover target transcripts of barley miRNAs a modified 5' RLM
      RACE was performed and seven cleaved miRNA transcripts were retrieved from
      drought stressed leaf samples. In silico analysis indicated 15 potential EST
      targets. Measurement of expression levels showed a positive correlation between
      levels of miRNA expression and suppression of their target mRNA transcripts in
      dehydration-stress-treated barley.

PMID- 20676717
TI  - The use of fibrin glue in the treatment of complex perianal fistulae: a case
      report.
AB  - We present a 71-year-old man with a horseshoe, complex perianal fistula. He was
      treated by a simple fistulotomy for the fistula at sixth hour, while fibrin
      sealant was applied for the complicated one. He is free of symptoms 24 months
      postoperatively.

PMID- 20676718
TI  - Perianal fistulas.
AB  - The most common cause of anal fistula is anal gland sepsis, resulting in
      formation of anorectal abscess, particularly if the latter allowed bursting
      spontaneously or has been inadequately opened at operation. Surgical treatment of
      the fistula must intent to its healing or simply its drainage or its
      transformation to a simpler one. Superficial, low transsphincteric and
      intersphincteric fistulas are treated by the lay-open technique. The use of a
      loose seton allows time for any sepsis and induration to settle before a decision
      about further treatment is made. Also, the use of a tight seton in the management
      of complex fistula may avoid an early muscle division before any tissue scarring
      happened. The patient with a perianal fistula must have a steady trustful
      relationship with his surgeon and must be fully informed on the therapeutic plan
      and reassured for a favourable outcome.

PMID- 20676719
TI  - Anuria in an infant secondary to bilateral ureteric stones.

PMID- 20676720
TI  - Convection in colloidal suspensions with particle-concentration-dependent
      viscosity.
AB  - The onset of thermal convection in a horizontal layer of a colloidal suspension
      is investigated in terms of a continuum model for binary-fluid mixtures where the
      viscosity depends on the local concentration of colloidal particles. With an
      increasing difference between the viscosity at the warmer and the colder boundary
      the threshold of convection is reduced in the range of positive values of the
      separation ratio psi with the onset of stationary convection as well as in the
      range of negative values of psi with an oscillatory Hopf bifurcation.
      Additionally the convection rolls are shifted downwards with respect to the
      center of the horizontal layer for stationary convection psi>0 and upwards for
      the Hopf bifurcation (psi<0.

PMID- 20676721
TI  - Time-dependent fluid squeeze-out between solids with rough surfaces.
AB  - We study the time dependency of the (average) interfacial separation between an
      elastic solid with a flat surface and a rigid solid with a randomly rough
      surface, squeezed together in a fluid. As an application we discuss fluid squeeze
      out between a tire tread block and a road surface. Some implications for the
      leakage of seals are discussed, and experimental results are presented to test
      the theory. The theoretical prediction for the leak rate as a function of the
      fluid pressure difference is in good agreement with the experimental data for all
      fluid pressures up to "lift-off", where the fluid pressure equals the nominal
      rubber-substrate squeezing pressure.

PMID- 20676722
TI  - Monte Carlo phase diagram for diblock copolymer melts.
AB  - The phase diagram for diblock copolymer melts is evaluated from lattice-based
      Monte Carlo simulations using parallel tempering, improving upon earlier
      simulations that used sequential temperature scans. This new approach locates the
      order-disorder transition (ODT) far more accurately by the occurrence of a sharp
      spike in the heat capacity. The present study also performs a more thorough
      investigation of finite-size effects, which reveals that the gyroid (G)
      morphology spontaneously forms in place of the perforated-lamellar (PL) phase
      identified in the earlier study. Nevertheless, there still remains a small region
      where the PL phase appears to be stable. Interestingly, the lamellar (L) phase
      next to this region exhibits a small population of transient perforations, which
      may explain previous scattering experiments suggesting a modulated-lamellar (ML)
      phase.

PMID- 20676723
TI  - Long-range interactions and wave patterns in a DNA model.
AB  - We propose a spin-like model of DNA nonlinear dynamics with long-range
      interactions between adjacent base pairs. We show that the model equation is a
      modified sine-Gordon equation. We perform the linear stability analysis of a
      plane wave, which predicts high-amplitude and extended oscillating waves for high
      values of the long-range parameter. This is confirmed numerically and biological
      implications of the obtained patterns are suggested.

PMID- 20676724
TI  - The role of key image notes in CT imaging study interpretation.
AB  - The objective of the study was to investigate the clinical effects of CT key
      image notes (KIN) in the interpretation of a CT image study. All experiments were
      approved by the ethics committee of the local district. Six experienced
      radiologists were equally divided into routine reporting (RR) group and KIN
      reporting (KIN) group. CT scans of each 100 consecutive cases before and after
      using KIN technique were randomly selected, and the reports were made by group RR
      and KIN, respectively. All the reports were again reviewed 3 months later by both
      groups. All the results with using or not using KIN were interpreted and
      reinterpreted after 3 months by six clinicians, who were experienced in picture
      archiving and communication system (PACS) applications and were equally divided
      into the clinical routine report group and the clinical KIN report group,
      respectively. The results were statistically analyzed; the time used in making a
      report, the re-reading time 3 months later, and the consistency of imaging
      interpretation were determined and compared between groups. After using KIN
      technique, the time used in making a report was significantly increased (8.77 +/-
      5.27 vs. 10.53 +/- 5.71 min, P < 0.05), the re-reading time was decreased (5.23
      +/- 2.54 vs. 4.99 +/- 1.70 min, P < 0.05), the clinical interpretation and
      reinterpretation time after 3 months were decreased, and the consistency of the
      interpretation, reinterpretation between different doctors in different time was
      markedly improved (P < 0.01). CT report with KIN technique in PACS can
      significantly improve the consistency of the interpretation and efficiency in
      routine clinical work.

PMID- 20676726
TI  - Cover essay: my Jerusalem, my EcoHell.

PMID- 20676725
TI  - YqhC regulates transcription of the adjacent Escherichia coli genes yqhD and dkgA
      that are involved in furfural tolerance.
AB  - Previous results have demonstrated that the silencing of adjacent genes encoding
      NADPH-dependent furfural oxidoreductases (yqhD dkgA) is responsible for increased
      furfural tolerance in an E. coli strain EMFR9 [Miller et al., Appl Environ
      Microbiol 75:4315-4323, 2009]. This gene silencing is now reported to result from
      the spontaneous insertion of an IS10 into the coding region of yqhC, an upstream
      gene. YqhC shares homology with transcriptional regulators belonging to the
      AraC/XylS family and was shown to act as a positive regulator of the adjacent
      operon encoding YqhD and DkgA. Regulation was demonstrated by constructing a
      chromosomal deletion of yqhC, a firefly luciferase reporter plasmid for yqhC, and
      by a direct comparison of furfural resistance and NADPH-dependent furfural
      reductase activity. Closely related bacteria contain yqhC, yqhD, and dkgA
      orthologs in the same arrangement as in E. coli LY180. Orthologs of yqhC are also
      present in more distantly related Gram-negative bacteria. Disruption of yqhC
      offers a useful approach to increase furfural tolerance in bacteria.

PMID- 20676727
TI  - Differential kinetics of alpha-[11C]methyl-L-tryptophan on PET in low-grade brain
      tumors.
AB  - Increased tryptophan metabolism via the kynurenine pathway is a major mechanism
      of tumor immuno-resistance. alpha-[(11)C]Methyl-L: -tryptophan (AMT) is a
      positron emission tomography (PET) tracer for tryptophan catabolism, and
      increased AMT uptake has been demonstrated in brain tumors. In this study we
      evaluated the use of AMT PET for detection of low-grade gliomas and glioneuronal
      tumors, and determined if kinetic parameters of AMT uptake can differentiate
      among tumor types. AMT PET images were obtained in 23 patients with newly
      diagnosed low-grade brain tumors (WHO grade II gliomas and WHO grade I
      dysembryoplastic neuroepithelial tumors [DNETs]). Kinetic variables, including
      the unidirectional uptake rate (K-complex) and volume of distribution (VD; which
      characterizes tracer transport), were measured using a graphical approach from
      tumor dynamic PET and blood-input data, and metabolic rates ([Formula: see text])
      were also calculated. These values as well as tumor/cortex ratios were compared
      across tumor types. AMT PET showed increased tumor/cortex K-complex (n = 16)
      and/or VD ratios (n = 15) in 21/23 patients (91%), including 11/13 tumors with no
      gadolinium enhancement on MRI. No increases in AMT were seen in an
      oligodendroglioma and a DNET. Astrocytomas and oligoastrocytomas showed higher
      [Formula: see text] tumor/cortex ratios (1.66 +/- 0.46) than oligodendrogliomas
      (0.96 +/- 0.21; P = 0.001) and DNETs (0.75 +/- 0.39; P < 0.001). These results
      demonstrate that AMT PET identifies most low-grade gliomas and DNETs by high
      uptake, even if these tumors are not contrast-enhancing on MRI. Kinetic analysis
      of AMT uptake shows significantly higher tumor/cortex tryptophan metabolic ratios
      in astrocytomas and oligoastrocytomas in comparison with oligodendrogliomas and
      DNETs.

PMID- 20676728
TI  - Kitten-transmitted Bordetella bronchiseptica infection in a patient receiving
      temozolomide for glioblastoma.
AB  - Bordetella bronchiseptica is a gram negative coccobacillus that can be
      transmitted from domestic animals and cause severe infections in
      immunocompromised patients. A 56-year-old man with a left parietal glioblastoma
      was treated with resection, radiation and concomitant and adjuvant temozolomide
      chemotherapy. He received bevacizumab for progression, and dose dense metronomic
      temozolomide was added for additional progression. He developed chronic cough and
      was diagnosed with B. bronchiseptica infection. This is the first reported case
      of B. bronchiseptica infection in a patient receiving temozolomide. The infection
      was likely acquired from an infected kitten. Patients receiving temozolomide
      should be counseled on the risks of acquiring zoonotic infections, including B.
      bronchiseptica, from their pets.

PMID- 20676729
TI  - Central nervous system Hodgkin lymphoma: case report and review of the
      literature.
AB  - Central nervous system (CNS) involvement by Hodgkin lymphoma (HL) is extremely
      rare, accounting for 0.5% or less of HL cases. In contrast, CNS involvement can
      occur in 5-30% of patients with non-Hodgkin lymphoma. CNS HL can present at any
      point in the course of HL, most commonly during relapsing disease, and has been
      described in both immunocompromised and immunocompetent patients. We describe a
      case of HL affecting the CNS and bone marrow on initial presentation in a 79-year
      old immunocompetent female with a prior history of squamous cell carcinoma of the
      larynx and adenocarcinoma of the lung. Following the case report, a review of the
      literature on CNS HL is presented.

PMID- 20676730
TI  - Congenital iris ectropion associated with juvenile glaucoma.
AB  - Congenital iris ectropion is an uncommon malformation of the anterior segment of
      the eye. The authors describe a case of bilateral congenital iris ectropion
      associated with juvenile glaucoma in an otherwise healthy 9-year-old girl. Intra
      ocular pressure (IOP) measured by Goldmann applanation tonometry was 40 mmHg in
      the right eye and 32 mmHg in the left eye. Despite maximum IOP lowering therapy,
      the desired IOP levels needed to prevent further progression of the glaucoma
      could not be achieved. Visual field testing and confocal scanning laser
      tomography showed glaucomatous neuropathy. Trabeculectomy with antimetabolites
      (mitomycin C 0.2 mg/ml) was performed in both eyes and IOP was normalized without
      IOP lowering medications during a follow-up of 4 years. The authors point out the
      importance of recognizing congenital iris ectropion early to prevent blindness in
      young patients and improve their prognosis.

PMID- 20676731
TI  - On the calibration of a size-structured population model from experimental data.
AB  - The aim of this work is twofold. First, we survey the techniques developed in
      Perthame and Zubelli (Inverse Probl 23(3):1037-1052, 2007), Doumic et al.
      (Inverse Probl 25, 2009) to reconstruct the division (birth) rate from the cell
      volume distribution data in certain structured population structured population
      models. Secondly, we implement such techniques on experimental cell volume
      distributions available in the literature so as to validate the theoretical and
      numerical results. As a proof of concept, we use the experimental data
      experimental data reported in the classical work of Kubitschek (Biophys J
      9(6):792-809, 1969) concerning Escherichia coli in vitro experiments measured by
      means of a Coulter transducer-multichannel analyzer system (Coulter Electronics,
      Inc., Hialeah, FL, USA). Despite the rather old measurement technology, the
      reconstructed division rates still display potentially useful biological
      features.

PMID- 20676732
TI  - Mathematical modeling in wound healing, bone regeneration and tissue engineering.
AB  - The processes of wound healing and bone regeneration and problems in tissue
      engineering have been an active area for mathematical modeling in the last
      decade. Here we review a selection of recent models which aim at deriving
      strategies for improved healing. In wound healing, the models have particularly
      focused on the inflammatory response in order to improve the healing of chronic
      wound. For bone regeneration, the mathematical models have been applied to design
      optimal and new treatment strategies for normal and specific cases of impaired
      fracture healing. For the field of tissue engineering, we focus on mathematical
      models that analyze the interplay between cells and their biochemical cues within
      the scaffold to ensure optimal nutrient transport and maximal tissue production.
      Finally, we briefly comment on numerical issues arising from simulations of these
      mathematical models.

PMID- 20676733
TI  - Biodegradation of 4-chlorophenol by Arthrobacter chlorophenolicus A6: effect of
      culture conditions and degradation kinetics.
AB  - Among known microbial species, Arthrobacter chlorophenolicus A6 has shown very
      good potential to treat phenolic wastewaters. In this study, the levels of
      various culture conditions, namely initial pH, agitation (rpm), temperature (
      degrees C), and inoculum age (h) were optimized to enhance 4-chlorophenol (4-CP)
      biodegradation and the culture specific growth rate. For optimization, central
      composite design of experiments followed by response surface methodology (RSM)
      was applied. Results showed that among the four independent variables, i.e., pH,
      agitation (rpm), temperature ( degrees C), and inoculum age (h) investigated in
      this study, interaction effect between agitation and inoculum age as well as that
      between agitation and temperature were significant on both 4-CP biodegradation
      efficiency and culture specific growth rate. Also, at the RSM optimized settings
      of 7.5 pH, 207 rpm, 29.6 degrees C and 39.5 h inoculum age, 100% biodegradation
      of 4-CP at a high initial concentration of 300 mg l(-1) was achieved within a
      short span of 18.5 h of culture. The enhancement in the 4-CP biodegradation
      efficiency was found to be 23% higher than that obtained at the unoptimized
      settings of the culture conditions. Results of batch growth kinetics of A.
      chlorophenolicus A6 for various 4-CP initial concentrations revealed that the
      culture followed substrate inhibition kinetics. Biokinetic constants involved in
      the process were estimated by fitting the experimental data to several models
      available from the literature.

PMID- 20676734
TI  - Obesogenic high fat western diet induces oxidative stress and apoptosis in rat
      heart.
AB  - Feeding Wistar rats a high calorie "Western" diet (45% fat) for up to 48 weeks
      induces obesity and cardiac dysfunction, while a high fat diet (60% fat) induces
      obesity only. Here we investigated the molecular "footprints" of the two forms of
      diet-induced obesity in the heart. In rats fed Western diet for a long term,
      cardiac mRNA transcript levels of malic enzyme were decreased (-72%, P < 0.05),
      suggesting impaired anaplerotic flux of the Krebs cycle (KC) and mitochondrial
      dysfunction. In addition, there was a marked decrease in the expression of the
      transcription factor MEF2C (myocyte enhancer factor 2C) and its target gene
      SERCA2a (sarco-endo-plasmic reticulum Ca(2+)-ATPase). Oxidative stress was
      reflected in reduced transcript levels of manganese superoxide dismutase,
      glutathione peroxidase 1, and increased protein levels of mitochondrial
      transcription factor A, suggesting compensatory mitochondrial biogenesis in the
      face of increased mitochondrial damage. Oxidant injury was accompanied by
      increased protein glycosylation, increased transcript levels of glutamine
      fructose 6-phosphate amidotransferase 2, and decreased protein levels of acetyl
      Co-A carboxylase. Lastly, apoptosis was evident by TUNEL positivity and elevated
      mRNA transcript levels and activity of caspase 3. Consistent with these results,
      protein levels of Bcl2 were markedly reduced. We conclude that inadequate
      supplementation of KC intermediates due to reduced levels of malic enzyme,
      downregulation of MEF2C and its target gene SERCA2a, oxidative stress, and
      programmed cell death are all potential contributors to contractile dysfunction
      of the heart.

PMID- 20676735
TI  - Microneedle pre-treatment of human skin improves 5-aminolevulininc acid (ALA)-
      and 5-aminolevulinic acid methyl ester (MAL)-induced PpIX production for topical
      photodynamic therapy without increase in pain or erythema.
AB  - PURPOSE: To determine the impact of skin pretreatment with microneedles (MNs) on
      ALA- and MAL-induced protoporphyrin IX (PpIX) production, as well as MN impact on
      pain sensations during light exposure and erythema after PDT. METHODS: The skin
      of 14 healthy volunteers was preteated with MNs. Equal amounts of creams
      containing 2%, 8% and 16% (w/w) ALA and MAL were applied on 1 cm(2) areas for 4
      h. Additionally, 16% ALA and MAL creams were applied for 24 h. Afterwards, PpIX
      fluorescence spectra were measured. Sixteen percent ALA and MAL spots were
      exposed to red light (632 nm, 77 mW/cm(2)). Time for pain to occur was measured
      in seconds, and erythemal response was monitored up to 6 h after the end of the
      light exposure. RESULTS: Use of MNs increased the PpIX fluorescence after 4 h
      incubation time with 2% and 8% ALA or MAL, but not with 16% ALA or MAL.
      Pretreatment with MNs did not increase the pain sensations during light exposure,
      nor did it influence erythema occurrence. CONCLUSIONS: MNs are a promising tool
      for improving the efficiency of topical PDT by improving the cutaneous delivery
      of ALA and MAL, without increase in side effects.

PMID- 20676736
TI  - Biorelevant media to simulate fluids in the ascending colon of humans and their
      usefulness in predicting intracolonic drug solubility.
AB  - PURPOSE: To develop media simulating human colonic fluids (HCFs), to evaluate
      their use in predicting intracolonic solubility of ketoconazole, danazol and
      felodipine and to compare solubilities in HCFs with previously determined
      solubilities in gastric (HGFs) and small intestinal (HIFs) fluids. METHODS:
      Fasted state simulated colonic fluid (FaSSCoF) and fed state simulated colonic
      fluid (FeSSCoF) were designed to reflect fluids previously collected from the
      ascending colon in healthy adults. Solubilities of the three model compounds were
      determined in HCFs, simulated HCFs, and plain buffers. RESULTS: For ketoconazole,
      solubilities in FaSSCoF and FeSSCoF were closer than those in the corresponding
      plain buffers to the solubility in HCFs. For danazol and felodipine, solubilities
      in FaSSCoF and FeSSCoF predicted solubilities in HCFs. In the fasted state,
      solubilities of danazol and felodipine in HCFs were higher than or similar to in
      HGFs or HIFs, while the ketoconazole solubility was lower. In the fed state,
      solubilities of all three model compounds in HCFs were lower than in HGFs or
      HIFs. CONCLUSIONS: FaSSCoF and FeSSCoF more closely predict solubility of poorly
      soluble compounds in HCFs than plain buffers. In most cases, solubility in HCFs
      differs from those in HGFs and HIFs.

PMID- 20676737
TI  - Ultrastructural localization of fibrillin-1 and fibrillin-2 in oxytalan fibers in
      periodontal ligament of Japanese Macaca fuscata monkey.
AB  - Although oxytalan fibers are a ubiquitous component of the periodontal ligament,
      their composition and function remain to be fully clarified. The purpose of this
      study was to investigate the localization of fibrillin-1 and fibrillin-2, large
      cysteine-rich glycoproteins, in monkey molar periodontal ligament by means of
      immunohistochemistry and electron microscopic immunogold labeling. Fibers
      positive for both fibrillin-1 and -2 were observed throughout the periodontal
      ligament, and their pattern of distribution was basically the same as that of
      oxytalan fibers. Double immunogold electron microscopy revealed that fibrillin-1
      co-localized with fibrillin-2 on the microfibrils of the oxytalan fibers. The
      results suggest that oxytalan fibers in monkey periodontal ligament are made up
      of fibrillin-rich microfibrils. These results should contribute to a better
      understanding of the role of oxytalan fibers in development and tissue remodeling
      in periodontal ligament.

PMID- 20676738
TI  - Photoluminescence of rare earth phosphors Na0.5Gd 0.5WO4: RE3+ and Na 0.5Gd
      0.5(Mo0.75W0.25)O4: RE3+ (RE=Eu, Sm, Dy).
AB  - Two series of phosphors, Na(0.5)Gd(0.5)WO(4): RE(3+) and
      Na(0.5)Gd(0.5)(Mo(0.75)W(0.25))O(4): RE(3+) (RE = Eu, Sm, Dy) have been
      synthesized by hydrothermal process to obtain the high purity, which have been
      characterized by X-ray powder diffraction (XRD), scanning electron microscope
      (SEM). The results suggest that Na(0.5)Gd(0.5)(Mo(0.75)W(0.25))O(4): RE(3+)
      phosphors are more easily to crystallize than Na(0.5)Gd(0.5)WO(4): RE(3+) ones.
      Both of them present the characteristic luminescence of Eu(3+), Sm(3+) and
      Dy(3+). Especially the photoluminescent properties of Na(0.5)Gd(0.5)WO(4):
      x%Eu(3+) (Sm(3+)) can be obtained to show white luminescence as the suitable
      doping concentration of Eu(3+) or Sm(3+).

PMID- 20676739
TI  - Grafting orchids and ugly: theatre, disability and arts-based health research.
AB  - Theatre-based health policy research is an emerging field, and this article
      investigates the work of one of its leaders. In 2005, prominent medical
      geneticist and playwright Jeff Nisker and his collaborators produced Orchids, his
      play concerning pre-implantation genetic diagnosis, to research theatre as a tool
      for engaging citizens in health policy development. Juxtaposing Orchids with a
      concurrent disability theatre production in Vancouver entitled Ugly, I argue that
      disability theatre suggests important means for building inclusiveness in this
      kind of research and complicates Nisker's own call for international guidelines
      to delimit how journalists, playwrights, filmmakers, physicians and other media
      authors share genetics-based narratives in public.

PMID- 20676740
TI  - Characterization of canine dendritic cells in healthy, atopic, and non-allergic
      inflamed skin.
AB  - Atopic dermatitis in humans and dogs is a chronic relapsing allergic skin
      disease. Dogs show a spontaneous disease similar to the human counterpart and
      represent a model to improve our understanding of the immunological mechanisms,
      the pathogenesis of the disease, and new therapy development. The aim of the
      study was to determine the frequency and phenotype of dendritic cells (DC) in the
      epidermis and dermis of healthy, canine atopic dermatitis lesional, and non
      allergic inflammatory skin to further validate the model and to obtain insights
      into the contribution of DC to the pathogenesis of skin diseases in dogs. We
      first characterized canine skin DC using flow-cytometric analysis of isolated
      skin DC combined with an immunohistochemical approach. A major population of
      canine skin dendritic cells was identified as CD1c(+)CD11c(+)CD14(
      )CD80(+)MHCII(+)MAC387(-) cells, with dermal DC but not Langerhans cells
      expressing CD11b. In the epidermis of lesional canine atopic dermatitis and non
      allergic inflammatory skin, we found significantly more dendritic cells compared
      with nonlesional and control skin. Only in canine atopic dermatitis skin did we
      find a subset of dendritic cells positive for IgE, in the epidermis and the
      dermis. Under all inflammatory conditions, dermal dendritic cells expressed more
      CD14 and CD206. MAC387(+) putative macrophages were absent in healthy but present
      in inflamed skin, in particular during non-allergic diseases. This study permits
      a phenotypic identification and differentiation of canine skin dendritic cells
      and has identified markers and changes in dendritic cells and macrophage
      populations related to allergic and non-allergic inflammatory conditions. Our
      data suggest the participation of dendritic cells in the pathogenesis of canine
      atopic dermatitis similar to human atopic dermatitis and further validate the
      only non-murine spontaneous animal model for this disease.

PMID- 20676741
TI  - Bidirectional associations between sibling relationships and parental support
      during adolescence.
AB  - Sibling relationships and parental support are important for adolescents'
      development and well-being, yet both are likely to change during adolescence.
      Since adolescents participate in both the sibling relationship and the parent
      child relationship, we can expect sibling relationships and parental support to
      be associated with each other. Theoretically, it can be expected that there is
      either a spillover from one relationship to another (congruence hypothesis) or
      that one relationship can compensate for the other (compensation hypothesis).
      However, research examining these associations in adolescence is limited. The
      present study longitudinally investigated the bidirectional associations between
      sibling relationships and parental support during adolescence. For five
      consecutive years, data were collected using self-reports of 428 families,
      consisting of a father, a mother, and two adolescent siblings. The mean ages of
      the first-born (52.8% males) and second-born (47.7% males) were 15 and 13 years
      at T1, respectively. For the second-born siblings, prospective associations were
      found between sibling relationships and adolescent-reported parental support in
      early adolescence, with no differences between same-sex and mixed-sex dyads.
      These associations were not found for first-born siblings or for parents' reports
      of support. The findings suggest a spillover from the sibling relationship to
      adolescent-reported parental support only in early adolescence. Findings and
      implications are discussed in terms of the congruence/spillover and the
      compensation hypothesis.

PMID- 20676742
TI  - C-reactive protein induces TNF-alpha secretion by p38 MAPK-TLR4 signal pathway in
      rat vascular smooth muscle cells.
AB  - Atherosclerosis is a chronic inflammatory disease. C-reactive protein (CRP) not
      only is an inflammatory marker but also regulates the expressions of other
      inflammatory cytokines associated with the pathogenesis of atherosclerosis. Toll
      like receptor 4 (TLR4) also contributes to atherogenesis via transducting
      inflammatory signals. Herein, our studies focused on characterizing the effect of
      CRP on tumor necrosis factor alpha (TNF-alpha) production and TLR4-related
      molecular mechanisms in rat vascular smooth muscle cells (VSMCs). The results
      showed that CRP stimulated VSMCs to secrete TNF-alpha and enhanced TLR4
      expression in a time-concentration-dependent manner. TLR4 knockdown significantly
      inhibited CRP-induced TNF-alpha generation, and p38 mitogen-activated protein
      kinase (MAPK) blocker SB203580 depressed TLR4 expression and TNF-alpha production
      initiated by CRP in VSMCs. The data demonstrate that CRP triggers an inflammatory
      response in rat VSMCs by inducing TNF-alpha secretion, which is mediated by p38
      MAPK-TLR4 signaling pathway.

PMID- 20676743
TI  - Bevacizumab-induced small bowel perforation in a patient with breast cancer
      without intraabdominal metastases.
AB  - A 53-years-old woman presented with sudden abdominal pain. One year before, she
      was diagnosed an inflammatory ductal carcinoma of the left breast (T3N0M0) and
      received 6 cycles of epirubicin and cyclophosphamide followed by 9 cycles of
      paclitaxel. A radical left mastectomy with lymphadenectomy was performed. On
      histopathology, the invasive ductal carcinoma was poorly differentiated,
      histological grade III without lymphovascular emboli, expressing E-cadherin, with
      negative hormone receptors status and no HER-2 overexpression. The final staging
      after chemotherapy was pT3N1M0, necessitating an adjuvant radiotherapy. Four
      months postoperatively, a CT-scan revealed liver and lung metastases and
      chemotherapy combining gemcitabine, oxaliplatin and bevacizumab was started for
      13 days when she suddenly developed severe abdominal pain. A CT-scan showed a
      pneumoperitoneum. She had a median laparotomy confirming the diagnosis of
      peritonitis by digestive perforation without ovarian, uterine, lymphatic, or
      peritoneal carcinomatosis. Assessment of the totality of the gastrointestinal
      tract showed two distinct punched out perforations of the small bowel, without
      macroscopic signs of tumor or metastases: one on the jejunum at 50 cm from the
      Treitz and the second at 10 cm of the end of the ileum. Small bowel resection
      with jejunojejunostomy and a lateral ileostomy were performed. Regarding the
      macroscopical pathological findings, the mucosa showed an ulceration measuring of
      1 cm without tumor. On microscopy we found a tranparietal neoplastic
      infiltration. Vessels were morphologically normal with tumoral cells' morphology
      and architecture identical to the primary breast carcinoma. Chemotherapy was not
      reintroduced after surgery and the patient died on the 57th postoperative day.

PMID- 20676744
TI  - VEGF pathway inhibition by anticancer agent sunitinib and susceptibility to
      atherosclerosis plaque disruption.
AB  - Patients treated with anti-VEGF agents are at increased risk for arterial thrombo
      embolic events (ATEs). However, the pathophysiology of such acute vascular
      complications remains unclear. We report on a case of bowel infarction in a renal
      cancer patient treated with the anti-VEGF agent sunitinib. An abdominal CT-scan
      evidenced the rupture of an atherosclerotic plaque located at the emergence of
      the superior mesenteric artery. In view of this report, we suggest that
      evaluation of the risk of ATE in patients receiving anti-VEGF agents should
      include not only age and past history of ATE as suggested by previous studies,
      but also assessment of atherosclerotic lesions on CT-scan.

PMID- 20676745
TI  - YC-1, a novel potential anticancer agent, inhibit multidrug-resistant protein via
      cGMP-dependent pathway.
AB  - The aim of the present study was to evaluate the effect of 3-(5'-hydroxymethyl-2'
      furyl)-1-benzylindazole (YC-1) on multidrug resistance. Expression of human P
      glycoprotein was assessed by realtime quantitative RT-PCR and western blot. The
      efflux function of P-glycoprotein was evaluated by rhodamine 123 accumulation and
      calcein-AM uptake models. The mechanisms of action of YC-1 on different signaling
      pathways were studied using series of antagonists and the kinetics was also
      assessed. Cytotoxicity was evaluated by MTT assay. The results demonstrated that
      increased intracellular accumulation of rhodamine 123 and increased fluorescence
      of calcein were observed after YC-1 treatment. Furthermore, increased YC-1
      concentration resulted in significant decrease in Vmax while K(M) remained
      unchanged suggested that YC-1 acted as a noncompetitive inhibitor of P
      glycoprotein. Moreover, the inhibition of Pgp efflux function by YC-1 was
      significantly reversed by NO synthase inhibitor, (L)-NAME, the sGC inhibitor,
      ODQ, the PKG inhibitor, Rp-8-Br-PET-cGMPS, and the PKG inhibitor KT5823. In
      addition, ERK kinase inhibitor PD98059 also significantly restored YC-1 inhibited
      Pgp efflux function. These results indicated that YC-1 inhibited Pgp efflux via
      the NO-cGMP-PKG-ERK signaling pathway through noncompetitive inhibition. The
      present study revealed that YC-1 could be a good candidate for development as a
      MDR modulator.

PMID- 20676746
TI  - Sonodynamic and photodynamic mechanisms of action of the novel hypocrellin
      sonosensitizer, SL017: mitochondrial cell death is attenuated by 11, 12
      epoxyeicosatrienoic acid.
AB  - Development of sonosensitizers for sonodynamic therapy (SDT) which selectively
      target abnormal cells can limit undesired side effects in chemotherapeutic
      applications. Hypocrellin-B (HB) derivatives are low molecular weight compounds
      which belong to the perylenequinone family of photosensitizing and
      sonosensitizing compounds. In this study, we investigate the cytotoxic mechanisms
      of a novel HB-derived photo- and sonosensitizer, SL017. Human fibroblast WI-38
      cells were treated with SL017 (0 MUM, 0.1 MUM or 10 MUM) and subjected to
      photodynamic therapy (PDT) or SDT. Studies demonstrate that maximal uptake of
      SL017 occurs within 30 min, with a mitochondrial subcellular localization.
      Activation of SL017 by either visible light or ultrasound resulted in significant
      increases in reactive oxygen species (ROS) production as measured by CM-H2-DCFDA
      (5-(and-6)-chloromethyl-2'7'-dichlorodihydrofluorescein diacetate acetyl ester).
      Co-administration of the antioxidant, ascorbic acid, attenuated ROS production.
      Low concentrations of SL017 (100 nM) induced a rapid (<90 s) loss of
      mitochondrial membrane potential (DeltaPsim). Epoxyeicosatrienoic acids (EETs),
      cytochrome P450-derived metabolites of arachidonic acid (AA) involved in
      maintaining homeostasis and protection against cell injury, were able to
      attenuate loss of DeltaPsim, however ascorbic acid was not. SL017 treatment
      resulted in increased mitochondrial fragmentation which followed loss of
      DeltaPsim. Our studies demonstrate that SL017 targets mitochondria, triggering
      collapse of mitochondrial membrane potential, generates ROS and subsequently
      results in mitochondrial fragmentation.

PMID- 20676747
TI  - Is it a bird? Is it a plane? category use in problem-solving in children with
      autism spectrum disorders.
AB  - Fourteen children with autism spectrum disorders (ASD) and fourteen age-matched
      typically-developing (TD) controls were tested on an adapted version of the
      Twenty Questions Task (Mosher and Hornsby in Studies in cognitive growth. Wiley,
      New York, pp 86-102, 1966) to examine effects of content, executive and verbal IQ
      factors on category use in problem-solving (age range 8-17). Across conditions
      participants with ASD asked questions that focussed on smaller categories than
      controls. Specific group differences were observed in the handling of abstract
      content and response to additional working memory demands. In addition, post hoc
      regression analysis indicated that VIQ predicted performance in ASD but not TD
      participants. The implications for theories of category processing in autism are
      discussed.

PMID- 20676748
TI  - Social networks and friendships at school: comparing children with and without
      ASD.
AB  - Self, peer and teacher reports of social relationships were examined for 60 high
      functioning children with ASD. Compared to a matched sample of typical children
      in the same classroom, children with ASD were more often on the periphery of
      their social networks, reported poorer quality friendships and had fewer
      reciprocal friendships. On the playground, children with ASD were mostly
      unengaged but playground engagement was not associated with peer, self, or
      teacher reports of social behavior. Twenty percent of children with ASD had a
      reciprocated friendship and also high social network status. Thus, while the
      majority of high functioning children with ASD struggle with peer relationships
      in general education classrooms, a small percentage of them appear to have social
      success.

PMID- 20676749
TI  - Complete nucleotide sequences of avian metapneumovirus subtype B genome.
AB  - Complete nucleotide sequences were determined for subtype B avian metapneumovirus
      (aMPV), the attenuated vaccine strain VCO3/50 and its parental pathogenic strain
      VCO3/60616. The genomes of both strains comprised 13,508 nucleotides (nt), with a
      42-nt leader at the 3'-end and a 46-nt trailer at the 5'-end. The genome contains
      eight genes in the order 3'-N-P-M-F-M2-SH-G-L-5', which is the same order shown
      in the other metapneumoviruses. The genes are flanked on either side by conserved
      transcriptional start and stop signals and have intergenic sequences varying in
      length from 1 to 88 nt. Comparison of nt and predicted amino acid (aa) sequences
      of VCO3/60616 with those of other metapneumoviruses revealed higher homology with
      aMPV subtype A virus than with other metapneumoviruses. A total of 18 nt and 10
      deduced aa differences were seen between the strains, and one or a combination of
      several differences could be associated with attenuation of VCO3/50.

PMID- 20676750
TI  - Application of touch FISH in the study of mosaic tetraploidy and maternal cell
      contamination in pregnancy losses.
AB  - PURPOSE: karyotype is a well established technique in the study of spontaneous
      miscarriages but is associated with selective overgrowth of maternal cells and
      other culture artefact (spp) such as tetraploidy, which could mask the true
      karyotype of the conceptus. METHODS: 328 cases of pregnancy losses were studied
      by karyotype and Multiplex Ligation Dependent Probe Amplification technique.
      Touch FISH performed in non-cultured cells was used to evaluate the ploidy
      complement and sex discrepancies using centromeric probes for chromosomes X, Y
      and 18. RESULTS: touch FISH confirmed 13 cases of maternal contamination,
      identified a triploidy and a monosomy X. True tetraploidy was confirmed in 7/14
      cases studied. CONCLUSION: touch FISH protocol is extremely accurate in the
      distinction of genuine mosaicism from tissue culture artifacts namely in cases
      with suspicion of tetraploidy and can be used to confirm maternal cell
      contamination in cases with sex discrepancy between karyotype and MLPA.

PMID- 20676751
TI  - Seminal plasma homocysteine, folate and cobalamin in men with obstructive and non
      obstructive azoospermia.
AB  - PURPOSE: The aim of this study was to analyze homocysteine, folate and cobalamin
      in men with normozoospermia, obstructive and non-obstructive azoospermia.
      METHODS: Analysis of plasma and seminal plasma homocysteine, folate and cobalamin
      in 72 azoospermic and 62 normozoospermic men. Evaluation of the azoospermic
      patient included testicular biopsy, endocrine, urological and ultrasound
      examination. RESULTS: Homocysteine (1.2 MUmol/l) and cobalamin (322.05 pmol/l)
      concentrations (median values) in seminal plasma were significantly lower (p <
      0.001) in men with azoospermia than in men with normozoospermia (2.5 MUmol/l and
      579.0 pmol/l). Folate and cobalamin concentrations were significantly higher in
      obstructive than in non-obstructive azoospermia. Significant correlations were
      determined between testis volume and seminal plasma homocysteine in azoospermic
      men. CONCLUSION: Lower concentrations of homocysteine and cobalamin (but not
      folate) were found in azoospermic seminal plasma than normozoospermic. Folate and
      cobalamin were higher in seminal plasma from obstructive azoospermia than in non
      obstructive azoospermia patients.

PMID- 20676752
TI  - Patient selection criteria for blastocyst culture in IVF/ICSI treatment.
AB  - BACKGROUND: The development and refinement of blastocyst media in recent years
      has allowed embryos to be cultured in-vitro for 5 or 6 days post oocyte retrieval
      and has been established as an effective selection tool to aid embryo selection
      for IVF treatment. It is generally accepted that blastocyst culture is not an
      appropriate option for all patients but the criteria for patient selection varies
      between clinics. Our blastocyst culture programme started in February 2005; the
      patient criteria was set at a minimum of 4 oocytes retrieved, a minimum of 4 2PN
      pronuclear embryos and at least 4 8-cell embryos of any quality on Day 3 where
      the female patient was 34 years and under. In the female age group of 35 years
      and over the criteria was at least 6 oocytes retrieved, a minimum of 6 2PN
      pronuclear embryos and at least 6 8-cell embryos of any quality on day 3.
      Improvements in pregnancy rates demonstrated the effectiveness of blastocyst
      transfer and clinical opinion was that the criteria should be adjusted to allow
      this option to be available to an increased patient population. From February
      2007 the blastocyst patient selection criteria was changed to at least 4 oocytes
      retrieved, at least 4 2PN pronuclear embryos and at least 2 8-cell and 2 6-cell
      or 7-cell embryos of top quality on Day 3 in women 38 years and under. For women
      39 years and over the criteria was lowered to at least 5 eggs retrieved, at least
      5 2PN and at least 3 8-cell embryos and 2 6-cell embryos of top quality on Day 3.
      METHODS: Retrospective statistical analysis was carried out to determine the
      pregnancy rates, live birth rates and twin rate for the period under the initial
      criteria and to examine the impact that lowering the criteria for patient
      selection for blastocyst culture had on these parameters. RESULTS: There was an
      overall fall in the ongoing pregnancy/live birth rate from 50.9% under the old
      criteria to 45.0% under the new criteria. However, the patients who had
      blastocyst culture under the new criteria but would have had day-3 embryo
      transfer under the initial criteria had a significantly increased live
      birth/ongoing pregnancy rate from 22.7% to 40.7%. There is an increase in the
      number of blastocyst culture cycles from 26.4% under the old criteria to 39.1%
      with the refined criteria. The twin pregnancy rate was reduced from 25.2% to
      17.5%. CONCLUSION: The result of this cohort study revealed that lowering the
      blastocyst selection criteria may lead to a lower overall clinical live birth
      rate from blastocyst culture; however, it will benefit a specific group of
      patients to achieve a better pregnancy and live birth rate. Furthermore, it
      increases the number of patients who will benefit from the blastocyst culture
      programme and also reduces multiple pregnancy rate.

PMID- 20676753
TI  - A case study of participatory action research in a public new England middle
      school: empowerment, constraints and challenges.
AB  - PAR recognizes teachers and students as co-creators in a learning process that
      builds self-efficacy essential to long-term educational success. In enabling
      contexts, PAR projects also allow teachers to critically deconstruct societal
      power, examine how these dynamics are reproduced in the classroom, and work
      against the silencing of student voices. This case study describes the process of
      implementing an inquiry-based PAR model into a formal urban middle school program
      intended to reduce drop out rates. The anthropologist/researchers employed
      participant observation, interviews, and review of student work to explore the
      dynamics, challenges, and constraints confronted during the process. The
      intervention demonstrated the gap between practice and theory in a middle school
      environment marked by well-defined hierarchies and roles as well as high-stakes
      testing.

PMID- 20676754
TI  - Participatory action research (PAR) in middle school: opportunities, constraints,
      and key processes.
AB  - Late childhood and early adolescence represent a critical transition in the
      developmental and academic trajectory of youth, a time in which there is an
      upsurge in academic disengagement and psychopathology. PAR projects that can
      promote youth's sense of meaningful engagement in school and a sense of efficacy
      and mattering can be particularly powerful given the challenges of this
      developmental stage. In the present study, we draw on data from our own
      collaborative implementation of PAR projects in secondary schools to consider two
      central questions: (1) How do features of middle school settings and the
      developmental characteristics of the youth promote or inhibit the processes,
      outcomes, and sustainability of the PAR endeavor? and (2) How can the broad
      principles and concepts of PAR be effectively translated into specific
      intervention activities in schools, both within and outside of the classroom? In
      particular, we discuss a participatory research project conducted with 6th and
      7th graders at an urban middle school as a means of highlighting the
      opportunities, constraints, and lessons learned in our efforts to contribute to
      the high-quality implementation and evaluation of PAR in diverse urban public
      schools.

PMID- 20676755
TI  - Genetic variants in COX-2, non-steroidal anti-inflammatory drugs, and breast
      cancer risk: the Western New York Exposures and Breast Cancer (WEB) Study.
AB  - Chronic inflammation has been consistently associated with cancers of several
      sites, including the breast, and inhibition of inflammation through the use of
      non-steroidal anti-inflammatory drugs (NSAIDs) has been inversely associated with
      risk. As NSAIDs bind with cyclooxygenase-2 (COX-2), genetic variation in COX-2
      may influence breast cancer risk by affecting inflammatory response and response
      to NSAID use. We identified eight single nucleotide polymorphisms (SNPs) for COX
      2 and examined their association with risk of breast cancer in a population-based
      case-control study in Western New York. Cases had incident, first primary,
      histologically confirmed breast cancer (n = 1077). Controls (n = 1910) were
      randomly selected from NY Department of Motor Vehicles records (< 65) or Medicare
      rolls (>= 65). Participants were queried on adult lifetime use of aspirin and
      recent use of ibuprofen. Unconditional logistic regression was used to estimate
      odds ratios (OR) and 95% confidence intervals (95% CI). One SNP, rs2745559, was
      associated with an increased risk of breast cancer (OR 1.23, 95% CI 1.03-1.46).
      Associations with other variants were not evident. Significant interaction (P
      interaction = 0.04) between recent aspirin use and rs4648261 was also observed.
      Variation in COX-2 was modestly associated with breast cancer risk, indicating
      that COX-2 may play a role in breast carcinogenesis. Better understanding of the
      role of COX-2 genetic variation and interaction with NSAID use in breast
      carcinogenesis has potential to inform prevention strategies.

PMID- 20676758
TI  - Glycodelin expression associates with differential tumour phenotype and outcome
      in sporadic and familial non-BRCA1/2 breast cancer patients.
AB  - Glycodelin (encoded by PAEP gene) is a secreted lipocalin protein mainly
      expressed in reproductive tissues, but also in several tumour types. In the
      breast, glycodelin is expressed both in normal epithelial and cancerous tissue.
      To investigate the association of glycodelin with clinicopathological features of
      breast cancer and outcome of patients we evaluated the protein expression of
      glycodelin in a large series of breast tumours. Immunohistochemical analysis of
      tissue microarrays was used to study glycodelin expression on 399 sporadic and
      436 familial non-BRCA1/2 tumours with strong family history. Gene expression
      analysis was used to define genes co-expressed with PAEP in sporadic and familial
      non-BRCA1/2 breast tumours. In the sporadic series, the glycodelin expression
      associated with low proliferation rate (P < 0.001), with a tendency towards well
      differentiated tumours (grades 1 and 2, P = 0.012) and high cyclin D1 (P = 0.034)
      expression. However, in familial non-BRCA1/2 cases with strong family history
      glycodelin expression associated with a less favourable phenotype, i.e. positive
      lymph node status (P = 0.003) and HER2-positive tumours (P = 0.009). Moreover,
      the patients with glycodelin-positive tumours had an increased risk for distant
      metastases (P = 0.001) and in multivariate analysis glycodelin expression was an
      independent predictor of metastasis (hazard ratio (HR) = 2.22, 95% confidence
      interval (95% CI) = 1.22-4.03, P = 0.009) in familial non-BRCA1/2 breast cancer.
      Gene expression analysis further revealed different gene expression profiles
      correlating with the PAEP expression in the sporadic and familial non-BRCA1/2
      breast cancers. Our findings suggest differential progression pathways in the
      sporadic and familial non-BRCA1/2 breast tumours expressing glycodelin.

PMID- 20676756
TI  - Prevalence of the variant allele rs61764370 T>G in the 3'UTR of KRAS among Dutch
      BRCA1, BRCA2 and non-BRCA1/BRCA2 breast cancer families.
AB  - Recently, a variant allele in the 3'UTR of the KRAS gene (rs61764370 T>G) was
      shown to be associated with an increased risk for developing non-small cell lung
      cancer, as well as ovarian cancer, and was most enriched in ovarian cancer
      patients from hereditary breast and ovarian cancer families. This functional
      variant has been shown to disrupt a let-7 miRNA binding site leading to increased
      expression of KRAS in vitro. In the current study, we have genotyped this KRAS
      variant in breast cancer index cases from 268 BRCA1 families, 89 BRCA2 families,
      685 non-BRCA1/BRCA2 families, and 797 geographically matched controls. The allele
      frequency of the KRAS-variant was found to be increased among patients with
      breast cancer from BRCA1, but not BRCA2 or non-BRCA1/BRCA2 families as compared
      to controls. As BRCA1 carriers mostly develop ER-negative breast cancers, we also
      examined the variant allele frequency among indexes from non-BRCA1/BRCA2 families
      with ER-negative breast cancer. The prevalence of the KRAS-variant was, however,
      not significantly increased as compared to controls, suggesting that the variant
      allele not just simply associates with ER-negative breast cancer. Subsequent
      expansion of the number of BRCA1 carriers with breast cancer by including other
      family members in addition to the index cases resulted in loss of significance
      for the association between the variant allele and mutant BRCA1 breast cancer. In
      this same cohort, the KRAS-variant did not appear to modify breast cancer risk
      for BRCA1 carriers. Importantly, results from the current study suggest that KRAS
      variant frequencies might be increased among BRCA1 carriers, but solid proof
      requires confirmation in a larger cohort of BRCA1 carriers.

PMID- 20676759
TI  - Influence of medium consumption on cell elasticity.
AB  - The mechanical behavior of a living cell is highly dynamic and constantly adapts
      to its local environment. Changes in temperature and chemical stimuli, such as
      pH, may alter the structure of the cell and its mechanical response. Thus, the
      mechanical properties may serve as an indicator for the cellular state. We
      applied dielectrophoretic forces to suspension cells by means of two
      microelectrodes. The resultant stretching was analyzed on consecutive cultivation
      days with respect to the influence of medium consumption. Systematic experiments
      clearly showed that the medium consumption affected the viscoelastic properties
      of the investigated human leukemia cells HL-60. The shift in pH value and the
      culture medium depletion were identified as potentially responsible for the
      differing temporal development of the cell deformation. Both factors were
      investigated separately and a detailed analysis indicated that the changes
      observed in the cellular stiffness were primarily attributable to nutrient
      depletion.

PMID- 20676760
TI  - Recombinant avian leukosis viruses of subgroup J isolated from field infected
      commercial layer chickens with hemangioma and myeloid leukosis possess an
      insertion in the E element.
AB  - BACKGROUND: Five isolates (JS09GY2, JS09GY3, JS09GY4, JS09GY5, and JS09GY6) of
      avian leukosis virus subgroup J (ALV-J) were isolated from six infected
      commercial layer flocks displaying both hemangioma and myeloid leukosis (ML),
      which shared the same parental line, in China in 2009. RESULTS: All six of the
      commercial layer chickens examined showed hemangiomas on their body surface or
      feet. Some developed hemangiomas in their internal organs, causing hepatorrhexis
      and blood loss. Histopathologically different stages of hemangiomas with ML in
      the liver, heart, and spleen, were observed. Five viral isolates were obtained
      from infected DF1 cells incubated with the spleen tissue or serum of the birds
      from the six flocks. By full genome sequences analysis, a 19-nucleotide repeat
      sequence was identified in the primer binding site (PBS)-leader region of
      isolates JS09GY3 and JS09GY6, located between sites 249 and 250 according to the
      sequence of reference strain HPRS103, and also present in Rous sarcoma virus
      strain Schmidt-Ruppin B (RSV-SRB), Rous associated virus type 1 (RAV-1), and Rous
      associated virus type 2 (RAV-2). The predicted Gp85 proteins of isolates JS09GY2,
      JS09GY3, JS09GY5, and JS09GY6 were highly variable. Interestingly, the E elements
      of these four examined isolates showed a key deletion at site 30, which produced
      a new c-Ets-1 binding site. An 11-bp insertion was also found in the E element of
      isolate JS09GY3 located between bp 66 and 67 according to the sequence of
      reference strain HPRS103, while almost all previously reported Chinese strains
      showed an almost identical deletion of 127 bp in the same region. CONCLUSIONS:
      Five ALV-J isolates were obtained from six field infected commercial layer
      chickens. Coexistence of hemangioma and ML were observed in these infected cases
      both macro- and microscopically. Complete proviral genome sequences of two
      isolates (JS09GY3 and JS09GY6) and the partial sequences of the other two
      isolates (JS09GY2 and JS09GY5) were determined. The isolates were found to be
      recombinants of ALV-J with a PBS-leader sequence originating from other
      retroviruses. The Gp85 protein with an amino acid deletion, a contiguous 11-bp
      insertion mutation in the E element, and a novel binding site, were noted in the
      proviral genomes.

PMID- 20676761
TI  - N-acetylpenicillamine inhibits the replication of porcine reproductive and
      respiratory syndrome virus in vitro.
AB  - Nitric oxide (NO) was proposed to be an important molecule against some
      microorganisms. In this study, we investigated the inhibitory effect of NO on the
      infection by porcine reproductive and respiratory syndrome virus (PRRSV) in vitro
      and the role of NO in the defense against PRRSV. Our results indicated that
      exogenous NO did not inhibit PRRSV infection. Unexpectedly, N-acetylpenicillamine
      (NAP), a commonly used compound as negative control for NO-producing reagents,
      inhibited PRRSV replication. Thus, the inhibition effect of NAP on PRRSV
      replication was further explored. We found that the maximal inhibition effect of
      NAP on PRRSV replication was achieved upon treatment 1 h after virus infection
      and the virus yield was reduced by approximately 50 fold in the presence of 400
      muM NAP. An obvious inhibitory effect on viral RNA and protein synthesis was also
      observed. However, the inhibitory effect was only achieved at early phase of
      virus infection. The normal virus yield could be restored upon the removal of NAP
      treatment. The inhibitory effect might be caused by sulfhydryl-reducing capacity
      and metal chelating properties of NAP. These studies suggested that (i) NO
      production or NO synthase (NOS) expression profiling may not be a reliable index
      for the immune response to PRRSV; (ii) NAP could inhibit the replication of
      PRRSV.

PMID- 20676762
TI  - Detection rates of the swine torque teno viruses (TTVs), porcine circovirus type
      2 (PCV2) and hepatitis E virus (HEV) in the livers of pigs with hepatitis.
AB  - Porcine circovirus type 2 (PCV2) and hepatitis E virus (HEV) are the most
      recently recognized causes of infectious hepatitis of pigs and may or may not act
      independently in the development of the disease. Recently it has been suggested
      that swine torque teno viruses (TTVs), in co-infections with some swine viral
      pathogens, may potentiate the severity of disease. In order to search for
      virological cofactors associated with infectious hepatitis in pigs, we
      investigated the liver tissues, to determine the presence of TTVs, PCV2 and HEV
      of naturally infected pigs and analysed the prevalence of both genogroups of the
      TTVs in the hepatitis lesions. Histopathological techniques, nested-polymerase
      chain reactions (nPCRs), polymerase chain reaction (PCR) and one-step reverse
      transcriptase polymerase chain reaction (RT-PCR) were applied to detect hepatitis
      lesions, TTVs genogroups 1 and 2, PCV2 and HEV infection. Of the livers examined
      58% (29/50) had mild to moderate hepatitis and 74% (37/50), 56% (28/50) and 26%
      (13/50) samples were nPCR, PCR and RT-PCR positive for TTVs PCV2 and HEV
      respectively. TTVs were detected in 84% (16/19) of the samples which were
      determined to be of mild severity while present in almost all (90% or 9/10)
      samples identified as having moderate hepatitis lesions. Additionally, the livers
      of 12 out of 21 (57%) pigs without the hepatitis lesions were positive for TTVs.
      These results demonstrate an association between TTVs and infectious hepatitis of
      pigs in concomitant infections with PCV2 and/or HEV and indicated that TTVs may
      play a role as a cofactor in the pathogenesis of disease.

PMID- 20676763
TI  - Factors that influence the efficiency of beef and dairy cattle recording system
      in Kenya: A SWOT-AHP analysis.
AB  - Animal recording in Kenya is characterised by erratic producer participation and
      high drop-out rates from the national recording scheme. This study evaluates
      factors influencing efficiency of beef and dairy cattle recording system. Factors
      influencing efficiency of animal identification and registration, pedigree and
      performance recording, and genetic evaluation and information utilisation were
      generated using qualitative and participatory methods. Pairwise comparison of
      factors was done by strengths, weaknesses, opportunities and threats-analytical
      hierarchical process analysis and priority scores to determine their relative
      importance to the system calculated using Eigenvalue method. For identification
      and registration, and evaluation and information utilisation, external factors
      had high priority scores. For pedigree and performance recording, threats and
      weaknesses had the highest priority scores. Strengths factors could not sustain
      the required efficiency of the system. Weaknesses of the system predisposed it to
      threats. Available opportunities could be explored as interventions to restore
      efficiency in the system. Defensive strategies such as reorienting the system to
      offer utility benefits to recording, forming symbiotic and binding collaboration
      between recording organisations and NARS, and development of institutions to
      support recording were feasible.

PMID- 20676764
TI  - Prevalence of rabies antibodies in street and household dogs in Chandigarh,
      India.
AB  - The present study reports the first survey for the detection of antirabies
      antibodies in street and household dogs in India. We aimed to check the efficacy
      of control programs for the disease in the Union territory of Chandigarh. The
      serum samples were collected from 100 street and 50 household dogs and tested for
      the presence of antirabies antibodies by ELISA. As per WHO criteria, a titre of
      >0.5 IU/ml of antirabies antibody in serum samples was taken as the protective
      level. Protective antirabies antibody titre was found only in 1% of the street
      dogs and 16% of the pet dogs. The awareness among the pet dog owners about the
      antirabies vaccination schedule was low as 18% did not know the vaccination
      status of the dog and 66% had got the initial immunization done with only three
      doses and annual boosters were not given. A National Rabies Elimination Program
      needs to be launched as a collaborative venture by both medical and veterinary
      practitioners to curb this deadly disease. Also periodic surveys to test the
      status of antirabies IgG among dogs need to be carried out to ascertain the
      attainment of WHO protective levels.

PMID- 20676765
TI  - Risk behaviours for milk-borne diseases transmission along the milk chain in The
      Gambia and Senegal.
AB  - The objective of this study was the characterisation of the traditional milk
      chain in Western Region (The Gambia) and Kolda (Southern Senegal); and the
      analysis of milk chain actors' risk behaviours for milk-borne diseases
      transmission. For this purpose, cattle herds involved in milk production, milk
      collectors, milk vendors and small-scale milk processing units were surveyed in
      the two study sites. A similar general milk chain organisation was found in the
      two sites with some particularities in farm management, compliance with hygienic
      measures at different levels, treatment of milk and milk consumption patterns.
      This results in a variable degree of risk of consumers' exposure to milk-borne
      diseases. Although the quality of the milk has been improved with the development
      of small-scale milk processing units, serious efforts are still needed with
      respect to pasteurisation procedure and to change the mindset of consumers who
      prefer in their majority drinking raw milk, fresh or soured, without any prior
      treatment.

PMID- 20676766
TI  - Predictors of participation in community outpatient psychosocial rehabilitation
      in schizophrenia.
AB  - This study investigated demographic, clinical and neurocognitive factors
      predicting drop-out from an intensive, community outpatient psychosocial
      rehabilitation program for people with schizophrenia or schizoaffective disorder.
      One-hundred and twenty-seven outpatients with DSM-IV schizophrenia or
      schizoaffective disorder participated. Demographic variables of age, sex,
      education and race/ethnicity were recorded and formal symptom measures and a
      neurocognitive assessment consisting of measures of crystallized verbal ability,
      sustained visual vigilance, verbal learning, verbal fluency and problem-solving
      were administered at study entry. Thirty-seven percent of the sample dropped-out
      of the program. In a final multivariate model, younger age, and lower verbal
      fluency scores in clients with a history of a high number of hospitalizations
      predicted a greater likelihood of drop-out. The implications of these findings
      are discussed.

PMID- 20676767
TI  - Melatonin expresses powerful anti-inflammatory and antioxidant activities
      resulting in complete improvement of acetic-acid-induced colitis in rats.
AB  - INTRODUCTION: Increased free-radical production, decreased antioxidant capacity,
      and excessive inflammation are well-known features in the pathogenesis of
      inflammatory bowel disease. Melatonin is a powerful antioxidant and a scavenger
      of hydroxyl radicals. Melatonin has also been shown to have anti-inflammatory
      activities in tissues. Our study objective is to investigate the effects of
      melatonin on tissue inflammatory activities using an ulcerative colitis (UC)
      model induced by acetic acid (AA) in rats. METHODS: Wistar rats (n = 32) were
      divided into four groups. AA-induced colitis was performed in two of the groups,
      while the other two groups were injected with saline intrarectally. One of the AA
      induced colitis groups and one of the control groups were administered 100
      mg/kg/day melatonin intraperitoneally, and the pair groups were given saline.
      After 4 days, colonic changes were evaluated biochemically by measuring
      proinflammatory cytokines [tumor necrosis factor (TNF)-alpha, interleukin (IL)
      1beta, and IL-6], myeloperoxidase (MPO), malondialdehyde (MDA), glutathione
      (GSH), and superoxide dismutase (SOD) levels in tissue homogenates and by
      histopathological examination. RESULTS: AA caused colonic mucosal injury, whereas
      melatonin suppressed these changes in the AA-induced colitis group (P < 0.001).
      AA administration resulted in increased TNF-alpha, IL-1beta, IL-6, MPO, and MDA
      levels, and decreased GSH and SOD levels, whereas melatonin administration
      reversed these effects (all P < 0.001). CONCLUSIONS: The present study proposes
      that melatonin has a dual action as an effective anti-inflammatory and an
      antioxidant, and may be a hopeful therapeutic agent for UC.

PMID- 20676768
TI  - Efficacy of endoscopic ultrasound-guided drainage of pancreatic pseudocysts in a
      pediatric population.
AB  - BACKGROUND: While pancreatitis is uncommon in children, pseudocyst development
      can be a serious complication. Endoscopic drainage of pseudocysts is well
      established in adults. However, there are limited data regarding this procedure
      in a pediatric population. The objective of this study is to determine the safety
      and efficacy of endoscopic ultrasound-guided pseudocyst drainage in children.
      METHODS: The study group included children (age <18 years) who presented for
      endoscopic drainage of symptomatic pancreatic pseudocysts in whom endoscopic
      ultrasound (EUS) was performed. In those cases with EUS guidance, a 19-gauge
      needle was used to access the pseudocyst and place a guidewire under fluoroscopic
      visualization. Needle-knife diathermy and balloon dilation of the tract were
      performed with subsequent placement of double pig-tailed stents for drainage.
      RESULTS: Ten children with mean age of 11.8 years (range 4-17 years) were
      analyzed for pancreatic pseudocysts due to biliary pancreatitis (n = 4), trauma
      (n = 2), familial pancreatitis (n = 1), idiopathic pancreatitis (n = 2), and
      pancreas divisum (n = 1). In eight cases, EUS-guided puncture and stent placement
      was successful. In the remaining two cases, aspiration of cyst fluid until
      complete collapse was adequate. As experience increased with EUS examination in
      children, the therapeutic EUS scope alone was used in 50% of cases for the entire
      procedure. In all ten cases, successful transgastric endoscopic drainage of
      pseudocysts was achieved. CONCLUSIONS: Endoscopic drainage of symptomatic
      pancreatic pseudocysts can be achieved safely in children. EUS guidance
      facilitates optimal site of puncture as well as placement of transmural stents.

PMID- 20676769
TI  - The prevalence of cationic trypsinogen (PRSS1) and serine protease inhibitor,
      Kazal type 1 (SPINK1) gene mutations in Polish patients with alcoholic and
      idiopathic chronic pancreatitis.
AB  - BACKGROUND: The main cause of chronic pancreatitis (CP) is excessive alcohol
      consumption. On the other hand, only 5-10% of heavy drinkers develop chronic
      pancreatitis. We have only limited information regarding the pathogenic mechanism
      by which alcohol leads to the disease. Mutations of the PRSS1 and SPINK 1 have
      been mostly implicated in hereditary and idiopathic CP, but their presence in
      other types of this disease have also been reported. AIMS: The aim of the study
      was to determine the frequency of PRSS1 and SPINK1 mutations in patients with
      chronic alcoholic (ACP) and idiopathic pancreatitis (ICP) as well as to
      investigate their relation to the clinical course of the disease. METHODS: The
      study included 33 ACP and 14 ICP patients as well 46 healthy subjects. The
      diagnosis of CP was based on clinical data, ultrasound, and computed tomography.
      After isolation of DNA from peripheral blood two trypsinogen mutations were
      detected N29I and R122H by allelo-specific amplification polymerase chain
      reaction (ASA-PCR) and by the PCR-restriction fragment length polymorphism
      (RFLP). Beside this N34S mutation of SPINK1 was analyzed by PCR restriction
      fragment length polymorphism (PCR-RFLP). RESULTS: PRSS1 mutations have been
      detected in 11 (33%) patients with ACP. The frequency of the PRSS1 mutations was
      higher in patients with ACP than in controls (4.3%) (p < 0.001). The frequency of
      PRSS1 mutation was present in 21.4% of ICP patients, which was significantly
      higher (p < 0.05) than in controls. Overall, six (18%) SPINK1 mutations in ACP
      group have been detected. Among 14 patients with ICP, in four (28.6%) of them
      SPINK1 has been detected. The same mutations have also been found in three (6.5%)
      control subjects. The frequency of the N34S mutation was higher in patients with
      ICP than in the controls (p < 0.05), but the frequency of N34S mutation did not
      differ between ACP and the control group. No relations have been detected between
      PRSS1 and SPINK1 mutations presence and clinical course and complications of CP.
      CONCLUSIONS: Those preliminary data suggest the high prevalence of SPINK1 and
      PRSS1 mutations in the Polish population, generally, as well as in CP patients.
      It may be speculated that those mutations contribute to the development of
      chronic pancreatitis, especially in patients with alcohol overindulgence.

PMID- 20676770
TI  - High prevalence of heartburn and low acid sensitivity in patients with idiopathic
      achalasia.
AB  - BACKGROUND: Heartburn is frequently reported by patients with achalasia before
      treatment. However, the esophageal sensitivity to acid as a possible mediator of
      this symptom has not been previously evaluated. AIM: To evaluate the prevalence
      of gastroesophageal reflux symptoms and the esophageal sensitivity to acid
      perfusion in patients with untreated achalasia. METHODS: Forty patients with
      achalasia were prospectively evaluated. Forty-three patients with
      gastroesophageal reflux disease comprised the control group (ten of them with
      Barrett's esophagus). Symptoms were evaluated by a structured clinical
      questionnaire. Objective assessment was performed by ambulatory 24-h esophageal
      pH monitoring and endoscopy. Esophageal sensitivity to acid was evaluated by
      esophageal perfusion of ClH 0.1 N. RESULTS: Fifteen (37%) of the 40 patients with
      achalasia presented heartburn, but only four of them had esophagitis and/or
      abnormal esophageal pH recording. Eight patients had abnormal pH recording. Three
      patients had esophagitis. The esophagus was sensitive to acid in seven (17%)
      patients with achalasia, three of them with heartburn and one with abnormal pH
      recording. In the control group, 40 of 43 (93%) presented heartburn. Acid
      perfusion was positive in 32 (74%). Sensitivity to acid was lower in patients
      with achalasia than in those with gastroesophageal reflux disease with or without
      Barrett's esophagus. CONCLUSIONS: The prevalence of heartburn in patients with
      achalasia is high, although its association with objective indicators of
      gastroesophageal reflux disease is weak. Patients with achalasia have lower
      esophageal sensitivity to acid than patients with GERD, suggesting that heartburn
      is does not arise from this condition.

PMID- 20676771
TI  - A multicenter, randomized study to evaluate the efficacy and safety of mesalamine
      suppositories 1 g at bedtime and 500 mg Twice daily in patients with active mild
      to-moderate ulcerative proctitis.
AB  - BACKGROUND: Ulcerative proctitis (UP) is a prevalent condition associated with
      increased morbidity and mortality. Topical mesalamine (5-aminosalicylic acid [5
      ASA]) inhibits inflammatory processes in UP. METHODS: We evaluated effects of
      mesalamine 1-g suppository administered QHS compared with 500-mg suppository
      administered BID on UP activity (e.g., disease extension/mucosal appearance),
      remission, onset of response, safety and compliance in 97 patients with UP. A 6
      week, randomized, multicenter, parallel-group, noninferiority study was conducted
      (and published) with Disease Activity Index (DAI) at week 6 as the primary
      efficacy variable and individual components of DAI at week 6 (i.e., stool
      frequency, rectal bleeding, mucosal appearance, global assessment) as secondary
      variables. Unreported outcomes were remission (DAI < 3 at weeks 3 and 6), disease
      extension, and complete response to treatment (DAI = 0; post-hoc, exploratory
      analysis). RESULTS: DAI values after 6 weeks were significantly reduced (+/-SD)
      from 6.6 +/- 1.5 to 1.6 +/- 2.3 (500-mg BID); and from 6.1 +/- 1.5 to 1.3 +/- 2.2
      (1-g QHS). Mucosal appearance significantly improved from baseline after 3 and 6
      weeks of treatment from 1.8 +/- 0.5 to 0.8 +/- 0.7 and 0.5 +/- 0.7 (500-mg BID; P
      <= 0.0062) and from 1.7 +/- 0.5 to 0.9 +/- 0.5 and 0.4 +/- 0.6 (1-g QHS; P <=
      0.0001), respectively. Remission was comparable (78.3-86.1%); onset of response
      generally occurred within 3 weeks, and disease extension was reduced (>70%) after
      6 weeks in both groups. Mesalamine was well tolerated. Compliance was >96%.
      CONCLUSIONS: Mesalamine 500-mg BID and 1-g QHS suppositories are safe and
      effective for patients with UP. Most patients reported significant improvement
      within 3 weeks and UP remission and reduced disease extension after 6 weeks of
      treatment. Validity of QHS administration was confirmed.

PMID- 20676772
TI  - After the primary endosymbiosis: an update on the chromalveolate hypothesis and
      the origins of algae with Chl c.
AB  - The chromalveolate hypothesis proposed by Cavalier-Smith (J Euk Microbiol 46:347
      366, 1999) suggested that all the algae with chlorophyll c (heterokonts,
      haptophytes, cryptophytes, and dinoflagellates), as well as the ciliates,
      apicomplexans, oomycetes, and other non-photosynthetic relatives, shared a common
      ancestor that acquired a chloroplast by secondary endosymbiosis of a red alga.
      Much of the evidence from plastid and nuclear genomes supports a red algal origin
      for plastids of the photosynthetic lineages, but the number of secondary
      endosymbioses and the number of plastid losses have not been resolved. The issue
      is complicated by the fact that nuclear genomes are mosaics of genes acquired
      over a very long time period, not only by vertical descent but also by
      endosymbiotic and horizontal gene transfer. Phylogenomic analysis of the
      available whole-genome data has suggested major alterations to our view of
      eukaryotic evolution, and given rise to alternative models. The next few years
      may see even more changes once a more representative collection of sequenced
      genomes becomes available.

PMID- 20676773
TI  - Designing bioactive delivery systems for tissue regeneration.
AB  - The direct infusion of macromolecules into defect sites generally does not impart
      adequate physiological responses. Without the protection of delivery systems,
      inductive molecules may likely redistribute away from their desired locale and
      are vulnerable to degradation. In order to achieve efficacy, large doses supplied
      at interval time periods are necessary, often at great expense and ensuing
      detrimental side effects. The selection of a delivery system plays an important
      role in the rate of re-growth and functionality of regenerating tissue: not only
      do the release kinetics of inductive molecules and their consequent bioactivities
      need to be considered, but also how the delivery system interacts and integrates
      with its surrounding host environment. In the current review, we describe the
      means of release of macromolecules from hydrogels, polymeric microspheres, and
      porous scaffolds along with the selection and utilization of bioactive delivery
      systems in a variety of tissue-engineering strategies.

PMID- 20676774
TI  - Cross species amplification ability of novel microsatellites isolated from
      Jatropha curcas and genetic relationship with sister taxa: cross species
      amplification and genetic relationship of Jatropha using novel microsatellites.
AB  - The present investigation was undertaken with an aim to check the ability of
      cross species amplification of microsatellite markers isolated from Jatropha
      curcas--a renewable source of biodiesel to deduce the generic relationship with
      its six sister taxa (J. glandulifera, J. gossypifolia, J. integerrima, J.
      multifida, J. podagrica, and J. tanjorensis). Out of the 49 markers checked 31
      markers showed cross species amplification in all the species studied. JCDS-30,
      JCDS-69, JCDS-26, JCMS-13 and JCMS-21 amplified in J. curcas. However, these
      markers did not show any cross species amplification. Overall percentage of
      polymorphism (PP) among the species studied was 38% and the mean genetic
      similarity (GS) was found to be 0.86. The highest PP (24) and least GS (0.76) was
      found between J. curcas/J. podagrica and J. curcas/J. multifida and least PP
      (4.44) and highest GS (0.96) was found between J. integerrima/J. tanjorensis.
      Dendrogram analysis showed good congruence to RAPD and AFLP than nrDNA ITS data
      reported earlier. The characterized microsatellites will pave way for
      intraspecies molecular characterization which can be further utilized in species
      differentiation, molecular identification, characterization of interspecific
      hybrids, exploitation of genetic resource management and genetic improvement of
      the species through marker assisted breeding for economically important traits.

PMID- 20676775
TI  - Can curative or life-sustaining treatment be withheld or withdrawn? The opinions
      and views of Indian palliative-care nurses and physicians.
AB  - INTRODUCTION: Decisions to withdraw or withhold curative or life-sustaining
      treatment can have a huge impact on the symptoms which the palliative-care team
      has to control. Palliative-care patients and their relatives may also turn to
      palliative-care physicians and nurses for advice regarding these treatments. We
      wanted to assess Indian palliative-care nurses and physicians' attitudes towards
      withholding and withdrawal of curative or life-sustaining treatment. METHOD: From
      May to September 2008, we interviewed 14 physicians and 13 nurses working in
      different palliative-care programmes in New Delhi, using a semi-structured
      questionnaire. For the interviews and analysis of the data we followed Grounded
      Theory methodology. RESULTS: Withholding a curative or life-sustaining treatment
      which may prolong a terminal cancer patient's life with a few weeks but also has
      severe side-effects was generally considered acceptable by the interviewees. The
      majority of the interviewees agreed that life-sustaining treatments can be
      withdrawn in a patient who is in an irreversible coma. The palliative-care
      physicians and nurses were of the opinion that a patient has the right to refuse
      life-saving curative treatment. While reflecting upon the ethical acceptability
      of withholding or withdrawal of curative or life-sustaining treatment, the
      physicians and nurses were concerned about the whole patient and other people who
      may be affected by the decision. They were convinced they can play an important
      advisory role in the decision-making process. CONCLUSION: While deciding about
      the ethical issues, the physicians and nurses do not restrict their
      considerations to the physical aspects of the disease, but also reflect upon the
      complex wider consequences of the treatment decisions.

PMID- 20676776
TI  - Euthanasia: agreeing to disagree?
AB  - In discussions about the legalisation of active, voluntary euthanasia it is
      sometimes claimed that what should happen in a liberal society is that the two
      sides in the debate "agree to disagree". This paper explores what is entailed by
      agreeing to disagree and shows that this is considerably more complicated than
      what is usually believed to be the case. Agreeing to disagree is philosophically
      problematic and will often lead to an unstable compromise.

PMID- 20676777
TI  - Lymphocytic hypophysitis in a patient presenting with sequential episodes of
      optic neuritis.
AB  - A 41-year-old man presented with left optic neuritis (ON) without evidence of
      other autoimmune disease or hormonal imbalance. MRI showed enlargement of the
      left optic nerve but no sellar lesion. The patient recovered after steroid
      therapy but later developed right ON and required treatment again. Follow-up MRI
      revealed an ill-defined, enlarging sellar lesion with enhancement extending into
      the right cavernous sinus, and the patient developed symptoms of fatigue and loss
      of libido. Hormonal studies revealed hypogonadism and hypocortisolism. All
      laboratory investigation for autoimmune and infectious diseases remained
      negative. A transsphenoidal biopsy of the lesion revealed lymphocytic
      hypophysitis. The concomitant development of lymphocytic hypophysitis and optic
      neuritis suggests a common and likely autoimmune etiology. Visual loss in
      patients with LYH can sometimes be due to ON rather than compression of the optic
      apparatus, with significant implications for treatment strategies.

PMID- 20676778
TI  - Effects of cabergoline on pregnancy and embryo-fetal development: retrospective
      study on 103 pregnancies and a review of the literature.
AB  - The aim of the study is to assess the rate of any potential adverse effects on
      women who became pregnant under cabergoline (CAB) treatment and to evaluate any
      effects on the embryo-fetal development and on children who were born from
      mothers exposed to CAB in early weeks of gestation. Observational, retrospective
      and multicenter study on 103 pregnancies in 90 women with hyperprolactinemia. All
      patients were under CAB at conception. Serum prolactin at baseline was between 30
      and 1921 ng/ml. Duration of therapy before pregnancy ranged from 1 to 120 months
      and doses ranged from 0.125 to 5 mg/week. Fetal exposure ranged from 3 to 25
      weeks, 96.9% of patients received CAB during the first trimester of pregnancy and
      the rest until the second one. No significant complications during pregnancy were
      found. Seven women (7.2%) had spontaneous abortions. Preterm deliveries were
      recorded in eight (8.8%), only one with low weight for gestational age. Neonatal
      abnormalities were observed in 3 (3.6%): 1 major (Down syndrome) and 2 minor
      malformations (umbilical and inguinal hernia). We were able to asses the
      children's development in 61. Two had epilepsy and two had Pervasive
      Developmental Disorder (PDD). No significantly higher frequency of complications
      was found in pregnancies and/or offspring exposed to CAB than in the normal
      population. We registered 2 abnormalities in the development of the children:
      epilepsy and PDD. Larger series of patients are needed to assess the safety of
      this drug during pregnancy.

PMID- 20676780
TI  - Sleep disorders among undergraduate students in Southern Brazil.
AB  - PURPOSE: Sleep disorders are very common in the young, being a result of the
      typical lifestyle lived by young people or a sleep disease that requires
      assistance and treatment. Furthermore, according to previous findings, sleep
      alterations can favor the development of depressive mood disorder. This survey
      aimed to assess the prevalence and characteristics of sleep disorders in a young
      population sample and their association with depressive symptoms. METHODS: With a
      cross-sectional study design, self-administered questionnaires were applied to
      1,180 undergraduate students. The Mini-Sleep Questionnaire (MSQ) and the Beck
      Depression Inventory were used to evaluate sleep disturbances and depressive
      symptoms, respectively. Bivariate and multivariate analyses were conducted, with
      the main findings being the presence of disrupted sleep (MSQ > 24), with an alpha
      error of 5%. The median point of the MSQ was 26 (P25-P75, 21-32 points). RESULTS:
      Sleep alterations were found in 59.6%. The prevalence of depression was 9.3% (n =
      110), mild depression being identified in 5.9% (n = 62), moderate in 3.4% (n =
      40), and severe in 0.7% (n = 8) of the students. In logistic regression, female
      gender (OR, 1.48; CI 95%, 1.09-2.01; P = 0.012) and being depressed (OR, 4.42; CI
      95%, 2.30-8.50; P < 0.001) were independent factors for disrupted sleep.
      CONCLUSIONS: Sleep alterations are prevalent complaints among young people, being
      present in nearly 60% of the students. Female gender and being depressed are
      independent factors for having some form of sleep disorder.

PMID- 20676782
TI  - Persistent spontaneous dissection of the left anterior descending coronary artery
      after emotional pressure.
AB  - A 51-year-old woman without cardiovascular risk factors experienced severe chest
      pain, accompanied by ST-segment elevation in lead II, III, AVF, and V4-V6. An
      immediately started thrombolytic therapy in a peripheral hospital successfully
      eliminated the cardiac symptoms and achieved complete ST-segment resolution.
      Subsequent cardiac angiography revealed a longitudinal spontaneous dissection in
      the distal part of the left anterior descending artery. Due to the small vessel
      size we decided on conservative therapeutic procedure with acetyl salicylamide,
      clopidogrel, statin, and beta blocker. Three months later, control angiography
      presented no resolution of the dissection and the patient showed excellent
      performance on stress test with no signs of ischemia.

PMID- 20676783
TI  - Percutaneous coronary intervention of an anomalous right coronary artery
      originating from the left coronary artery.
AB  - Anomalous origin of the right coronary artery is a rare congenital anomaly that
      was first described in 1948 by White and Edwards. It is well established that an
      anomalous origin of the right coronary artery can lead to angina pectoris,
      myocardial infarction, or sudden death, in the absence of atherosclerosis. Thus
      from the literature data it has been also suggested that the abnormal origin and
      course of anomalous coronary arteries could make them more prone to
      atherosclerosis due to altered flow patterns. We report our experience involving
      one patient who had significant atherosclerotic disease and was successfully
      treated with percutaneous coronary intervention (PCI) and stent implantation in
      an anomalous right coronary artery arising from the left coronary artery.

PMID- 20676784
TI  - Acute myocardial infarction involving two coronary arteries due to a patent
      foramen ovale.

PMID- 20676785
TI  - Autoimmune versus oligodendrogliopathy: the pathogenesis of multiple sclerosis.
AB  - Multiple sclerosis (MS) is the most common inflammatory demyelinating disease of
      the central nervous system (CNS); it affect millions of patients worldwide and
      the number of patients is on the rise. Current treatment options are fairly
      limited and there is a strong unmet need for disease-targeted therapies for MS.
      The most widely accepted hypothesis for the pathogenesis of MS is that it is a
      primary autoimmune disease in which myelin-specific T cells play a central role
      in the progression of demyelination. According to this hypothesis, a powerful
      immune suppression or a reconstruction of the immune system to abrogate disease
      specific leukocytes early in the development of the disease is expected to halt
      or even reverse the disease, since remyelination is an exceptionally efficient
      regenerative process in the CNS. However, recent neuropathological studies have
      provided evidence of primary oligodendrogliopathy as a cause of demyelination,
      suggesting that immune reactions may be a mere secondary event in the course of
      MS. On the other hand, some recent clinical trial results of new immune
      suppressive treatments showed a nearly complete blockade of relapses and
      significant, albeit incomplete, neurological improvement. Therefore, which
      hypothesis--autoimmunity or oligodendrogliopathy--lights the correct path to a
      "cure" for MS?

PMID- 20676787
TI  - Biological factors involved in implant-anchored orthodontics and in prosthetic
      implant therapy: a literature review.
AB  - During the past few years, the application of orthodontic miniscrews and dental
      implants has been expanded. However, failures have necessitated ongoing
      investigation of potential risk factors. The aim of this overview was to conduct
      an assessment of the immunological response following application of cortical
      temporary anchorage devices--titanium miniscrew implants--in orthodontic
      patients. A scrupulous search of the database revealed only two matching items;
      therefore studies evaluating the immune response subsequent to insertion of
      dental implants were reviewed. Thorough assessment revealed the following as
      factors associated with dental implant rejection: (1) correlation of the volume
      of gingival and peri-implant crevicular fluid and the amount of interleukin (IL)
      1beta with mucosal inflammation, thus serving as a peri-implantitis evaluation
      index; (2) significantly more frequent marginal bone loss around implants in
      patients with IL-1B-511 2/2 genotype; (3) humoral response to Staphylococcus
      aureus. However, since there is almost no evidence-based evaluation of the
      allergic/inflammatory reaction either to orthodontic titanium miniscrews
      themselves or in adolescents and young adults, who comprise the largest group of
      orthodontic patients, this issue requires further investigation. It is essential
      in order to achieve successful, sophisticated and modern treatment of
      malocclusions.

PMID- 20676786
TI  - Monocyte and macrophage abnormalities in systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with profound
      effects on multiple organ systems. In patients with SLE, the immune system is
      subverted to target numerous self antigens and the ensuing inflammatory response
      elicits a vicious cycle of immune-cell activation and tissue damage. Both genetic
      and environmental factors are essential for the development of this debilitating
      condition, although the exact cause remains unclear. Early studies on the
      pathogenesis of lupus centered on the adaptive immune system as lymphocyte
      abnormalities were thought to be the primary cause of autoimmunity. In the past
      decade, however, this paradigm has shifted with rapid advances in the field of
      innate immunity. These developments have yielded important insights into how the
      autoimmune response in SLE is initiated and maintained. Monocytes and macrophages
      are an essential arm of the innate immune system with a multitude of
      immunological functions, including antigen presentation, phagocytosis, and
      cytokine production. Aberrations of monocyte/macrophage phenotype and function
      are increasingly recognized in SLE and animal models of the disease. In this
      review we summarize the current knowledge of monocyte/macrophage abnormalities in
      human SLE and discuss their implications for understanding the pathogenesis of
      lupus.

PMID- 20676788
TI  - Evaluating causes of death in familial adenomatous polyposis.
AB  - BACKGROUND: Familial adenomatous polyposis is a genetic syndrome associated with
      an increased risk of colorectal cancer (CRC) and different extracolonic
      manifestations. GOALS: The goal of this study is to evaluate the frequency of
      death causes. MATERIAL AND METHODS: Charts from 97 patients treated from 1977 to
      2008 were reviewed. Retrieved data and family information allowed us to classify
      causes of death in those related to CCR to other malignancies or other causes.
      RESULTS: There were analyzed data from 46 men (47.4%) and 51 women (52.6%) with
      an average age of 35.1 years (14 to 82). At diagnosis, 57 patients (58.7%)
      already had CRC-associated polyposis. There were performed 93 colectomies, one
      internal diversion, and one partial resection. Two patients were not operated on.
      Results from 19 deceased patients (19.5%) were analyzed. CRC, other tumors
      (desmoid tumors, lymphoma, and gastric cancer), and other causes (complication of
      duodenal cancer surgery, complication after ileorectal anastomosis (IRA), and
      coronary disease) were responsible for 12 (63.1%), four (21.1%), and three
      (15.8%) of all deaths, respectively. Death from CRC occurred in the context of
      either systemic, rectal, or pouch recurrence. Desmoid disease was the second
      cause of death (10.5% of all causes), leading to a fatal outcome 22% of all
      patients who developed DT during the study period. Upper digestive carcinomas
      were responsible for other two death cases. CONCLUSIONS: (1) CRC is still the
      most prevalent cause of death; (2) even after curative resections, CRC can cause
      death through rectal or pouch malignization; (3) long-term survival was also
      strongly related to the development of extracolonic neoplasia, especially desmoid
      tumors and gastroduodenal carcinoma; (4) our results raise the need for local
      improvement in familiar screening and help us to define follow-up strategies and
      patient-information standards.

PMID- 20676790
TI  - Does body mass index/morbid obesity influence outcome in patients who undergo
      pancreatoduodenectomy for pancreatic adenocarcinoma?
AB  - INTRODUCTION: The obesity epidemic coupled with epidemiologic evidence of the
      link between pancreatic cancer and obesity has raised the interest in the impact
      of body mass index (BMI) on outcomes for resected pancreatic cancer. METHODS: All
      patients who underwent pancreatoduodenectomy (PD) for pancreatic adenocarcinoma
      from 1981 to 2007 were categorized into four groups according to their BMI (<25,
      25 to <30, 30 to <35, and >=35). Associations of these BMI groups with
      perioperative (operating time, blood loss, complications, in-hospital mortality),
      pathologic (tumor diameter, tumor stage, differentiation, lymph node status, R0
      status) features and long-term patient outcome were evaluated using Kruskal
      Wallis and chi-square tests, logistic regression, and Cox proportional hazards
      regression. A second set of analyses were performed by dichotomizing patients
      into morbidly obese (BMI >= 35) in comparison to the rest. RESULTS: Of the 586
      consecutive patients studied, there were 232 (39.6%) with BMI <25, 232 (39.6%)
      with BMI 25 to <30, 89 (15.2%) with BMI 30 to <35, and 33 (5.6%) with BMI >= 35.
      Operating time (P = 0.003) and intraoperative blood loss (P < 0.001) increased
      with BMI, although none of the remaining perioperative features differed
      significantly among the BMI groups. Similarly, there were no significant
      associations between BMI group and the pathological features studied,
      particularly lymph node status (P= 0.98). BMI was not associated with lymph node
      status even after adjusting for tumor diameter. All analyses were repeated for
      the morbidly obese. Cox regression did not demonstrate an impact of BMI or morbid
      obesity on overall or disease-free survival. CONCLUSIONS: BMI (and morbid
      obesity) does not appear to influence long-term outcomes for patients undergoing
      PD. Surgeons should be vigilant of the greater risk of perioperative blood loss
      with increasing BMI.

PMID- 20676791
TI  - Simultaneous liver and colorectal resections are safe for synchronous colorectal
      liver metastases.
AB  - BACKGROUND: Hepatic resection (HR) is the only option offering a potential cure
      for patients with synchronous colorectal cancer liver metastases (SCRLM). The
      optimal timing of HR for SCRLM is still controversial. This study aimed to
      determine whether simultaneous HR is similar to staged resection regarding the
      morbidity and mortality rates in patients with SCRLM. METHODS: Four hundred and
      five consecutive patients with SCRLM were treated with either simultaneous (n =
      129) or staged (n = 276) HR. The postoperative complications were analyzed
      retrospectively according to the documented records and hepatectomy databases at
      the Gastrointestinal Institute. RESULTS: Perioperative morbidity and mortality
      did not differ between simultaneous resections and staged resections for selected
      patients with SCRLM (morbidity, 47.3% versus 54.3%; mortality, 1.5% versus 2.0%,
      respectively; both p > 0.05). Simultaneous liver resections of three or more
      segments would not increase the rate of complications compared to staged
      resections (56.8% and 42.4%, respectively; p = 0.119). Meanwhile, patients with
      simultaneous resections experienced shorter duration of surgery and postoperative
      hospitalization time as well as less blood loss during surgery (all p < 0.05).
      CONCLUSIONS: Simultaneous resections of colorectal cancer primary lesions and
      hepatic metastases were safe and could serve as a primary option for selected
      SCRLM patients.

PMID- 20676792
TI  - Alternative port site selection (APSS) for improved cosmesis in laparoscopic
      surgery.
AB  - The use of laparoscopy can be associated with improved cosmesis following a
      variety of gastrointestinal procedures versus standard open surgery. The
      placement of laparoscopic ports in less visible areas of the body such as the
      bikini line, termed alternative port site selection (APSS), may result in further
      improved cosmesis. Performance of laparoscopic procedures from such alternative
      port placement areas may be associated with increased technical challenge. This
      manuscript discusses APSS approaches for two common laparoscopic procedures,
      cholecystectomy and gastric banding. Familiarity and implementation of these
      techniques can allow select patients to undergo procedures with less visible
      scarring and is less challenging than laparoscopic single site approaches.

PMID- 20676793
TI  - Surgeon volume versus morbidity and cost in patients undergoing
      pancreaticoduodenectomy in an academic community medical center.
AB  - BACKGROUND: Despite trends toward regionalization of care, the majority of
      pancreaticoduodenectomies (PD) are performed in community hospitals by surgeons
      with varying degrees of experience. We analyzed the impact of several variables,
      including surgeon volume, on outcomes following PD within a high-volume community
      based teaching hospital system. METHODS: Patients who underwent PD from 2005 to
      2008 were reviewed retrospectively. Perioperative data, complications, and
      hospital financial data was queried. A high-volume (HV) surgeon was defined as an
      average of 10 or more PD per year. RESULTS: Ninety-four patients underwent PD
      with an overall operative mortality rate of 9.6% (HV 2.2%, LV 16.0%), major
      complication rate of 32% (HV 18%, LV 44%), and median cost of $30,860 (HV
      $27,185, LV $33,007). Factors predictive of death were age (p < 0.02), body mass
      index (p < 0.01), and surgeon volume (p < 0.05). Factors predictive of major
      complication were surgeon volume (p < 0.01) and body mass index (p < 0.01).
      Factors predictive for increased length of stay for patients discharged from the
      hospital were surgeon volume (p < 0.02) and preoperative ASA classification (p <
      0.05). CONCLUSIONS: Surgeon volume and patient body mass index have a significant
      impact on perioperative morbidity following PD in a community teaching hospital.

PMID- 20676794
TI  - Large volume hepatic microwave ablation elicits fewer pulmonary changes than
      radiofrequency or cryotherapy.
AB  - BACKGROUND: Lung changes after microwave tissue ablation (MTA) of different
      volumes of liver were compared with hepatic resection, cryotherapy (CRYO) and
      radiofrequency ablation (RFA). METHODS: Live rats underwent MTA, surgical
      resection, CRYO or RFA of 15%, 33% and 66% of total hepatic volume and lung
      samples were collected at the time of death. Lung impairment was assessed
      directly by examining the tissue specimens for the degree of interstitial
      pneumonia and by comparing the alveolar thickness in the different groups.
      RESULTS: All RFA and CRYO rats undergoing 66% of ablations died, but the MTA
      group had no fatalities. Following 66% RFA or CRYO ablations, the animals had a
      significantly increased thickness of the alveolar septa compared to 15% or 33%
      ablations and to 66% ablations in the MTA group. CONCLUSIONS: Large volume MTA is
      associated with a significant reduction in consequent lung damage and is well
      tolerated compared to RFA and CRYO.

PMID- 20676795
TI  - CT and MR findings in a neuroforaminal extraskeletal Ewing sarcoma mimicking
      benign nerve sheath tumor.
AB  - INTRODUCTION: We report the CT and MR findings in a 30-year-old man with
      extraskeletal Ewing sarcoma (EES) involving the left neural foramen at L5-S1
      level. MATERIALS AND METHODS: The patient was evaluated with preoperative
      lumbosacral CT and MR imaging and postoperative lumbosacral MR imaging. RESULTS:
      The lesion was hyperdense on CT, isointense on T1- and T2-weighted MR images, and
      enhanced homogeneously after intravenous gadolinium injection. With these CT and
      MR findings, surgery was performed with a presumptive diagnosis of nerve sheath
      tumor, but the histopathological examination revealed EES. Chemotherapy and
      radiotherapy were planned postoperatively. CONCLUSION: This case illustrates that
      even in benign looking lesions in a neuroforamen one can never exclude
      malignancy, and this is even more true in a population of young adults.

PMID- 20676796
TI  - Secondary prevention for coronary artery disease: are we following the
      guidelines?
AB  - BACKGROUND: Secondary prevention pharmacotherapy in post-myocardial infarction
      (MI) patients reduces the risk of subsequent coronary events and overall
      mortality. International guidelines recommend use of aspirin, beta-blockers, ACE
      inhibitors and statins in post-MI patients. AIMS: We performed this audit to
      review the compliance of prescribing practices, in a regional hospital in
      Ireland, with international guidelines for secondary prevention of coronary
      artery disease. METHODS: We performed a retrospective case review of 172 patients
      diagnosed with MI during a 1-year period between January and December 2007.
      RESULTS: A total of 134 patients fulfilled the inclusion criteria. On discharge,
      aspirin was prescribed to 131 (97.76%) patients, clopidogrel to 126 (94%), beta
      blockers to 117 (87%), ACE inhibitor to 87 (65%), ARB to 10 (7%) and statins to
      116 (87%). CONCLUSION: Our audit shows that targets for prescription of secondary
      prevention medications were not met in a small but significant proportion of
      patients and calls for review of discharge practices and education to improve
      compliance with guidelines.

PMID- 20676797
TI  - The psychological impact of arthritis: the effects of illness perception and
      coping.
AB  - BACKGROUND: Coping and illness perception are considered to be important
      contributors in the relationship between physical and psychological factors in
      rheumatoid arthritis (RA). AIMS: The aim of this study was to examine the complex
      relationship of coping and illness perception on physical and psychological
      factors in RA using a structural model. METHODS: We assessed coping, illness
      perception, depression, anxiety, pain, arthritis-related disability and perceived
      social support in 68 adults with RA. RESULTS: Greater pain was detected in
      patients with increased scores on passive coping scale, greater severity of
      physical disability and increased depression and anxiety. Illness perception was
      found to be a mediator in the relationship between physical disability and
      passive coping on one hand and depression, anxiety and pain on the other.
      CONCLUSIONS: The hypothesised structural model has proven to be a useful paradigm
      for understanding the associations between multiple factors in RA presentation:
      clinical, emotional, personal and cognitive.

PMID- 20676798
TI  - Human exposure to arsenic, cadmium, mercury, and lead from foods in Catalonia,
      Spain: temporal trend.
AB  - The main purpose of this study was to establish the temporal trend in the daily
      dietary intake of arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) by the
      population of Catalonia, Spain. Concentrations of these elements were determined
      in samples of a number of food items widely consumed in that country. The dietary
      intake of As, Cd, Hg, and Pb was then estimated for various age-gender groups of
      population: children, adolescents, adults, and seniors. In the present study, the
      dietary intakes of As, inorganic As, Cd, Hg, methylmercury, and Pb were 328.37,
      16.22, 19.47, 11.39, 10.25, and 101.47 MUg/day, respectively, while in a previous
      (2006) survey, the dietary intakes of As, inorganic As, Cd, Hg, methylmercury,
      and Pb were 261.01, 33.17, 9.80, 12.61, 11.35, and 45.13 MUg/day, respectively.
      The estimated intakes of Cd, Hg, and Pb are still notably lower than the
      respective PTWIs, while that of inorganic As is also lower than its BMDL(01). In
      summary, the results of this study indicate that, currently, the dietary intakes
      of As, Cd, Hg, and Pb should not mean additional health risks for the consumers.

PMID- 20676799
TI  - The antioxidant and antigenotoxic effects of pycnogenol((r)) on rats treated with
      cisplatin.
AB  - Oxidative stress and inflammation are implicated in the pathogenesis of cisplatin
      induced toxicity. Pycnogenol(r) is known for its strong antioxidant and anti
      inflammatory effects. In this study, the possible protective effects of
      pycnogenol on kidney, bone marrow, and red blood cells in rats treated with
      cisplatin were investigated. The rats were divided into four groups. Group 1 was
      the control and groups 2, 3, and 4 were orally treated with pycnogenol (200 mg/kg
      bw, o.p) for 5 days, treated with cisplatin (7 mg/kg bw, i.p.) on the fifth day
      and treated with cisplatin plus pycnogenol, respectively. Antioxidative
      parameters in kidney and red blood cells were measured. Chromosome anomalies in
      bone marrow and renal histopathology were also investigated. Activities of pro
      oxidant enzymes (myeloperoxidase and xanthine oxidase), malondialdehyde, and
      nitric oxide levels significantly increased but antioxidant enzymes activities
      decreased in the kidneys and red blood cells after cisplatin treatment.
      Pycnogenol treatment prior to the administration of cisplatin significantly
      decreased cisplatin-induced injury, as evidenced by its normalizing these
      parameters. Chromosomal aberrations decreased and mitotic index frequencies
      increased in bone marrow treated with cisplatin plus pycnogenol. These findings
      suggest that pycnogenol may be a useful protective agent against the toxicity
      associated with cisplatin therapy.

PMID- 20676800
TI  - Redox buffer capacity of the cell: theoretical and experimental approach.
AB  - Reactive oxygen species (ROS) are involved in a variety of biological phenomena,
      such as mutation, carcinogenesis, inflammation, aging, development, and signal
      transduction. Intracellular generation of ROS might lead to the activation of
      redox signaling or oxidative stress. Nonetheless, it is difficult to estimate
      whether ROS-induced intracellular events are beneficial or deleterious to the
      cell. The quantitative basis of changes in the intracellular redox state of cells
      is not well-defined, thus leading to the dilemma that redox changes induced by
      oxidants in distinct cell types cannot be predicted. To overcome this limitation
      this study undertakes to analyze on a theoretical as well as on an experimental
      basis the intracellular redox state changes occurring inside cells upon addition
      of oxidants or reductants. 2,7-Dichlorodihydrofluorescein (H(2)DCF) was used to
      characterize the redox buffer capacity in erythrocytes. It was shown that the
      redox buffer capacity of erythrocytes in the relation to peroxynitrite (ONOO(-))
      is 2.1 times lower than the redox buffer capacity of erythrocytes in the relation
      to hydrogen peroxide (H(2)O(2)). The feasibility of redox buffer capacity
      assessment as an innovative tool for investigation and description of redox
      signaling events in cells is discussed.

PMID- 20676801
TI  - Biosynthesis of ribostamycin derivatives by reconstitution and heterologous
      expression of required gene sets.
AB  - Ribostamycin is a 4,5-disubstituted 2-deoxystreptamine (DOS)-containing
      aminoglycoside antibiotics and naturally produced by Streptomyces ribosidificus
      ATCC 21294. It is also an intermediate in the biosynthesis of butirosin and
      neomycin. In the biosynthesis of ribostamycin, DOS is glycosylated to generate
      paromamine which is converted to neamine by successive dehydrogenation followed
      by amination, and finally ribosylation of neamine gives ribostamycin. Here, we
      report the biosynthesis of 6'-deamino-6'-hydroxyribostamycin (a ribostamycin
      derivative or pseudoribostamycin) in Streptomyces venezuelae YJ003 by
      reconstructing gene cassettes for direct ribosylation of paromamine. A trace
      amount of pseudoribostamycin was detected with ribostamycin in the isolates of
      ribostamycin cosmid heterologously expressed in Streptomyces lividans TK24. It
      has also indicated that the ribosyltransferase can accept both neamine and
      paromamine. Thus, the present in vivo modification of ribostamycin could be
      useful for the production of hybrid compounds to defend against bacterial
      resistance to aminoglycosides.

PMID- 20676802
TI  - Effects of PACAP on oxidative stress-induced cell death in rat kidney and human
      hepatocyte cells.
AB  - Oxidative stress plays an important role in various renal and hepatic
      pathologies, and reduction of oxidative stress-induced processes is an important
      protective strategy in tissues of diverse origins against harmful stimuli.
      Pituitary adenylate cyclase activating polypeptide (PACAP) is a well-known
      cytotrophic and cytoprotective peptide. PACAP promotes cell survival in numerous
      cells and tissues exposed to various stimuli. Protective effects of PACAP have
      been shown in the kidney, but it is not known whether PACAP is protective against
      oxidative stress in renal cells. Little is known about the effects of PACAP in
      the liver. The aim of the present study was to investigate whether PACAP is
      protective against oxidative stress in primary rat kidney cell culture and
      whether PACAP has any effect on cell survival in human WRL-68 hepatocytes and HEP
      G2 hepatocellular carcinoma cells subjected to oxidative stress. Cells were
      exposed to various concentrations of H(2)O(2) with or without PACAP co-treatment
      and cell viability was evaluated with the 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyl tetrazolium bromide test (MTT). We found that oxidative stress induced a
      significant decrease in cell viability in both cell lines. PACAP could dose
      dependently increase the percentage of living cells in kidney cells, but it
      failed to do so in hepatocytes. Given the survival-promoting effects of PACAP
      against oxidative stress in rat kidney, we conducted a further experiment to
      determine whether PACAP influences the markers of oxidative stress in vivo. We
      have proven earlier that PACAP was effective in kidney ischemia/reperfusion
      injury in vivo. In the present study, we determined the levels of the oxidative
      stress marker malondialdehyde and the activity of the scavenger molecules
      glutathione (GSH) and superoxide dismutase (SOD) following kidney
      ischemia/reperfusion in rats. We found that PACAP significantly increased the
      level of GSH and counteracted the marked reduction of SOD activity after
      ischemia/reperfusion in vivo. In summary, the present study showed that while
      PACAP was able to significantly increase the cell survival in primary kidney cell
      cultures exposed to oxidative stress, possibly involving interaction with the
      endogenous scavenger system, it failed to influence the viability of normal or
      cancerous hepatocytes.

PMID- 20676803
TI  - Production of hepatopoietin Cn in high-cell-density cultures of recombinant
      Escherichia coli and detection of its antioxygen activity.
AB  - Hepatopoietin Cn (HPPCn), a member of the leucine-rich acidic nuclear protein
      (LANP) family, is a novel human hepatic growth factor that stimulates DNA
      synthesis and hepatocyte proliferation in vivo and in vitro by activating several
      signaling pathways. We performed pilot-scale production of recombinant human
      HPPCn (rhHPPCn) protein to elucidate its role in liver protection. An Escherichia
      coli BL21 (DE3) strain containing a pET-24a-HPPCn expression vector was
      cultivated in a 40-l bioreactor. High-cell-density fed-batch fermentation using
      this strain yielded a high concentration of rhHPPCn protein in the form of
      inclusion bodies. After washing and solubilization of the protein, rhHPPCn
      refolding was achieved by dilution of the denaturant. Then, the renatured protein
      was purified chromatographically. Assessment of the biological activity of the
      obtained protein showed that rhHPPCn could attenuate the oxidative stress in
      ethanol-induced hepatocyte injury. We successfully achieved large-scale
      production of biologically active rhHPPCn protein and obtained yields greater
      than 40 mg rhHPPCn per gram dry cell weight by applying the above-mentioned
      renaturation and purification procedures. The obtained volumetric yield
      corresponds to 640 mg of biologically active rhHPPCn per liter of culture broth.
      Additionally, the recombinant HPPCn protein was confirmed to protect hepatocytes
      against ethanol-induced oxidative stress.

PMID- 20676804
TI  - Tumor-associated macrophages infiltration is associated with peritumoral
      lymphangiogenesis and poor prognosis in lung adenocarcinoma.
AB  - Tumor-associated macrophages (TAMs) have been implicated in promoting tumor
      progression. Nowadays, adenocarcinoma has surpassed squamous cell carcinoma as
      the most frequent type of lung cancer, but in lung adenocarcinoma, the
      correlation of TAMs with lymphangiogenesis patients remains unclear. The aim of
      this study was to examine the relationship between TAMs and lymphangiogenesis and
      the lung adenocarcinoma patients' prognosis. Tumor specimens from 65 patients
      with lung adenocarcinoma were determined for TAMs count and lymphatic microvessel
      density (LMVD) by immunohistochemistry. A positive correlation existed between
      TAMs count and D2-40-positive peritumoral LMVD (r=0.069, P<0.001). TAMs
      infiltration was significantly associated with P-TNM staging (P=0.042) and lymph
      node metastasis (P=0.037), and peritumoral LMVD was correlated with lymph node
      metastasis (P=0.003). A significant difference in overall survival was detected
      not only between tumors with a high TAMs count and a low TAMs count (P=0.009) but
      also between tumors with a high peritumoral LMVD and a low peritumoral LMVD
      (P=0.005). Both TAMs count and peritumoral LMVD were independent prognostic
      factors for overall survival. Our results indicate that TAMs infiltration
      correlates with tumor lymphangiogenesis and poor survival in lung adenocarcinoma.

PMID- 20676806
TI  - Clinical trials report. Low-level laser therapy in the management of neck pain.

PMID- 20676805
TI  - The impact of obstructive sleep apnea on chronic kidney disease.
AB  - Obstructive sleep apnea (OSA) is an important clinical problem in the chronic
      kidney disease (CKD) population. OSA is associated with hypoxemia and sleep
      fragmentation, which activates the sympathetic nervous system, the renin
      angiotensin-aldosterone system, alters cardiovascular hemodynamics, and results
      in free radical generation. In turn, a variety of deleterious processes such as
      endothelial dysfunction, inflammation, platelet aggregation, atherosclerosis, and
      fibrosis are triggered, predisposing individuals to adverse cardiovascular events
      and likely renal damage. Independent of obesity, OSA is associated with
      glomerular hyperfiltration and may be an independent predictor of proteinuria, a
      risk factor for CKD progression. OSA is also associated with hypertension,
      another important risk factor for CKD progression, particularly proteinuric CKD.
      OSA may mediate renal damage via several mechanisms, and there is a need to
      better elucidate the impact of OSA on incident renal disease and CKD progression.

PMID- 20676807
TI  - Regulation of peripheral inflammation by the central nervous system.
AB  - In inflammatory disorders such as rheumatoid arthritis, cytokines and danger
      signals are sensed by the central nervous system, which adapts behavior and
      physiologic responses during systemic stress. The central nervous system can also
      signal the periphery to modulate inflammation through efferent hormonal and
      neuronal pathways. The brain and spinal cord are involved in this bidirectional
      interaction. A variety of neuronal pathways that modulate synovial inflammation
      have been implicated, including the sympathetic and the parasympathetic branches
      of the autonomic system. Another mechanism, the dorsal root reflex, involves
      antidromic signaling along somatic afferent fibers that influences joint
      inflammation by releasing neuropeptides and other neuromediators in the
      periphery. Some of the neurotransmitters and neuroreceptors involved have been
      identified in preclinical models and represent novel targets for the treatment of
      rheumatic diseases.

PMID- 20676808
TI  - Metabolic myopathies.
AB  - We consider recent developments in disorders affecting three areas of metabolism:
      glycogen, fatty acids, and the mitochondrial respiratory chain. Among the
      glycogenoses, new attention has been directed to defects of glycogen synthesis
      resulting in absence rather than excess of muscle glycogen ("aglycogenosis").
      These include defects of glycogen synthetase and defects of glycogenin, the
      primer of glycogen synthesis. Considerable progress also has been made in our
      understanding of alterations of glycogen metabolism that result in polyglucosan
      storage. Among the disorders of lipid metabolism, mutations in the genes encoding
      two triglyceride lipases acting hand in hand cause severe generalized lipid
      storage myopathy, one associated with ichthyosis (Chanarin-Dorfman syndrome), the
      other dominated by juvenile-onset weakness. For the mitochondrial myopathies, we
      discuss the importance of homoplasmic mitochondrial DNA mutations and review the
      rapid progress made in our understanding of the coenzyme Q(10) deficiencies,
      which are often treatable.

PMID- 20676809
TI  - Exciting new targets in lung cancer therapy: ALK, IGF-1R, HDAC, and Hh.
AB  - The anaplastic lymphoma kinase (ALK) inhibitor crizotinib will become an integral
      addition to the treatment of patients with non-small cell lung cancer (NSCLC)
      harboring genetic ALK translocations. The insulin-like growth factor receptor
      (IGF-1R) monoclonal antibody figitumumab, while initially promising, appears to
      increase toxicity and death in combination with chemotherapy in the treatment of
      patients with NSCLC of squamous histology; therefore, clinical development of
      this class of agents will need to proceed with caution. The histone deacetylation
      (HDAC) inhibitor vorinostat did not demonstrate an improvement in overall
      survival (OS) compared with placebo in a large randomized trial, but other agents
      in this class may have greater selectivity and efficacy. Inhibitors of the
      hedgehog (Hh) signaling pathways have some early clinical promise in both NSCLC
      and small cell lung cancer (SCLC), and larger studies using these agents are
      eagerly anticipated.

PMID- 20676810
TI  - In vitro quantification of wear in tibial inserts using microcomputed tomography.
AB  - BACKGROUND: Wear of polyethylene tibial inserts can decrease the longevity of
      total knee arthroplasty. Wear is currently assessed using laboratory methods that
      may not permit backside wear measurements or do not quantify surface deviation.
      QUESTIONS/PURPOSES: We developed and validated a technique to quantify
      polyethylene wear in tibial inserts using microcomputed tomography (micro-CT), a
      nondestructive high-resolution imaging technique that provides detailed images of
      surface geometry in addition to volumetric measurements. METHODS: Six unworn and
      six wear-simulated polyethylene tibial inserts were evaluated. Each insert was
      scanned three times using micro-CT at a resolution of 50 MUm. The insert surface
      was reconstructed for each scan and the insert volume was calculated. Gravimetric
      analysis was performed for all inserts, and the micro-CT and gravimetric volumes
      were compared to determine accuracy. We created three-dimensional surface
      deviation maps. RESULTS: Micro-CT generated high-quality three-dimensional
      renderings of the insert surface geometry. Between-scan precision was 0.07%; we
      observed no difference between micro-CT and gravimetric volume measurements.
      CONCLUSIONS: Micro-CT can provide precise and accurate volumetric measurements in
      addition to quantifiable three-dimensional surface deviation maps for the entire
      insert surface. The technique has the potential to evaluate wear in wear
      simulator trials and retrieval studies. CLINICAL RELEVANCE: This micro-CT
      technique combines the benefits of volumetric and surface scanning methods to
      quantify wear across all surfaces of polyethylene components with a single tool.
      When applied in wear simulator and retrieval studies, these measurements can be
      used to evaluate and predict the wear properties of the components.

PMID- 20676811
TI  - Solitary plasmacytoma of the thoracic vertebra presenting with sudden paraplegia
      and back pain: a pathologic case report.
AB  - Solitary plasmacytoma (SPC) accounts for 5% of plasma cell neoplasm. SPC of the
      spine is relatively rare, and SPC presenting with sudden paraplegia is very rare.
      A 53 year-old woman was admitted to our hospital complaining of sudden severe
      paraplegia and back pain. Emergency MRI revealed a tumor of the thoracic vertebra
      no. 10 (Th10). Pressure fracture of the Th10 was also recognized. The tumor was
      not osteolytic and invasion was recognized around the Th10. The tumor directly
      compressed the spinal cord. An excision of the tumor was performed under the
      clinical diagnosis of metastatic carcinoma. Pathologtically, the tumor consisted
      of plasmacytoid atypical cells with hyperchromatic nuclei. Histochemically, the
      tumor cells showed pyroninophilia. Immunohistochemically, the tumor cells were
      positive for lambda-light chain, but negative for cytokeratin, epithelial
      mermbrane antigen, vimentin, CD45, CD20, CD45RO, kappa-light chain, alpha-heavy
      chain, lambda-heavy chain, MU-heavy chain, delta-heavy chain, epsilon-heavy
      chain, IgA, IgG, IgM, synaptophysin, chromogranin, S100 protein, desmin, alpha
      smooth muscle antigen, myoglobin, and p53 protein. The Ki-67 labeling was 73%.
      The author diagnosed the tumor as SPC with lambda-light chain disease. After the
      diagnosis, whole body CT and MRI revealed no other tumors. Blood and serum test
      revealed no significant changes; no M-protein was recognized. However, voided
      urine test revealed lambda-light chain protein. The patient underwent fixation
      operation of TH10, and received radiation (50 Gray) and chemotherapy. No
      recurrence or transformation into myeloma occurred at the present time 25 months
      after the first manifestation. The present study indicated that pathological
      examination is an only clue to the diagnosis of SPC of the vertebra bone.

PMID- 20676812
TI  - The reproducibility of landmarks on three-dimensional images of 4- to 6-year-old
      children.
AB  - OBJECTIVE: The objective of this study was to check the reproducibility and
      influencing parameters of landmarks on three-dimensional images of 4- to 6-year
      old Caucasian children. PROBANDS AND METHODS: We examined the reproducibility of
      22 landmarks on six three-dimensional facial scans of 4- to 6-year-old randomly
      selected kindergarten children. The 3D scans were taken by the digital system
      faceSCAN II under standardized conditions. One specially-trained investigator
      marked all landmarks on each of the six 3D scans a total of ten times. Ten
      different orthodontic residents also placed all landmarks on each of these scans.
      Standard deviations from the mean were then calculated from the data for each
      individual landmark on the x-, y- and z-axes. RESULTS: The specially-trained
      investigator who had placed all landmarks on each of the six 3D scans a total of
      ten times found 15 of 22 landmarks to be reproducible well to within a standard
      deviation of less than 1 mm on each spatial plane. For the ten orthodontic
      residents, only three landmarks were found to be reproducible to within a
      standard deviation of under 1 mm for each spatial plane. CONCLUSION: Familiarity
      with 3D facial scans and their corresponding software programs, together with
      good image quality, improve the reproducibility of the analysis. Landmarks
      revealing poor reproducibility should be used, if at all, with due caution for
      analysis. It remains to be seen whether they can be omitted altogether, or
      whether they should be re-set.

PMID- 20676813
TI  - Comparison of a modified RME appliance with other appliances for transverse
      maxillary expansion.
AB  - AIM: Plate appliances or fixed appliances for transverse expansion are used to
      treat lateral crossbites in early mixed dentition. The aim of this study was to
      compare these appliances' dentoalveolar effects with those of a modified
      appliance with altered anchorage. PATIENTS AND METHODS: Forty patients with early
      mixed dentition were examined. Twenty patients in the study group were treated
      with a modified RME appliance firmly anchored to the first permanent molars and
      with palatal rests in the first and second deciduous molar region. The appliance
      had wire extensions to the palatal aspects of the canines. One of the two
      comparison groups comprised 10 patients whose maxillary dental arch was
      transversally expanded with a split-plate appliance, and the other group
      contained 10 patients treated with a Hyrax-type rapid palatal expander fixed to
      the first permanent molars. After the plaster casts' transverse parameters before
      and after expansion and after retention were measured to ascertain the treatment
      result, statistical analysis was performed applying the Wilcoxon test and Mann
      Whitney U test. RESULTS: The modified RME appliance expanded the anterior and
      posterior arch width highly significantly in transversal direction (p < 0.001).
      At the end of the retention phase, there were no significant differences between
      the modified RME appliance and the RME appliance with shortened arms. Compared to
      the split-plate appliance, the modified RME (p < 0.05) expanded the anterior arch
      width significantly. CONCLUSION: The modified RME appliance can be used
      effectively for rapid maxillary expansion in the early mixed dentition. At the
      end of the retention phase, the overall effect of the modified appliance is
      similar to that of the other methods.

PMID- 20676814
TI  - Spectrum of indications for palatal implants in treatment concepts involving
      immediate and conventional loading.
AB  - AIM: To analyze the spectrum of indications for second-generation palatal
      implants in relation to two different loading concepts in a prospective,
      multicenter, randomized controlled trial (RCT). PATIENTS AND METHODS: Forty-one
      patients were recruited to the study from 2006 to 2009. All implants
      (Orthosystem, Straumann, Basel, Switzerland; dimensions: 4.1 mm x 4.2 mm) were
      inserted in the median or paramedian region of the anterior palate, and each
      patient was randomized to one of two loading groups (immediate loading within the
      first week after insertion versus conventional loading after a 12-week healing
      phase). In this interim evaluation, we report preliminary results obtained six
      months after functional loading. RESULTS: All palatal implants were primarily
      stable at the time of insertion. One implant loss (12 weeks after surgical
      insertion) was documented in the cohort subjected to conventional loading, and
      one patient dropped out of the immediate-loading group. At the time of this
      investigation, 39 palatal implants are experiencing functional loads. Using both
      loading concepts, we had various orthodontic objectives, such as intrusion of
      anterior and/or posterior teeth, and the mesialization and distalization of
      posterior teeth. Both loading groups presented nearly identical indications, and
      the distribution of direct vs. indirect anchorage forms was also very similar
      during the active treatment. CONCLUSION: Comparison of the two treatment concepts
      revealed no clinical differences in implant stability. Patients undergoing
      immediate-loading therapy were subject to no limitations regarding indications at
      6 months after functional loading compared with the patients who experienced
      conventional loading.

PMID- 20676815
TI  - Effects of conventional anchorage on premolar root development during treatment
      with a pendulum appliance.
AB  - OBJECTIVE: By metrically analyzing orthopantomograms, we aimed in this study to
      retrospectively investigate whether maxillary premolars used as anchoring teeth
      during molar distalization with pendulum appliances would reveal inhibited root
      development. PATIENTS AND METHODS: The upper molars were distalized with a
      modified pendulum appliance (Pendulum K) in 36 adolescents (14 males, 22 females,
      mean age 12.3 years). Mean treatment period was 19.5 weeks. Orthopantomograms of
      each patient were taken at the start (time point T1) and after completion of
      molar distalization (time point T2). The enlargement of the posterior region was
      ascertained individually quadrant by quadrant for each radiograph, followed by
      measurement of the vestibular tooth lengths of the premolars whose root
      development was for the most part not yet complete. To assess further root
      development in the premolar region, the differences were calculated between tooth
      lengths at the start and end of treatment. RESULTS: During treatment with the
      pendulum appliance a general increase in tooth lengths in the anchorage region
      was observed (1.37 +/- 1.70 mm, p<0.0001). Differentiated by dental age, we noted
      increases in tooth lengths of patients with second molars in the budding stage
      (patient group PG 1: 0.93 +/- 1.37 mm, p<0.0001) as well as of patients with
      fully-erupted second molars (patient group PG 2: 1.81 +/- 1.88 mm, p<0.0001).
      Both groups demonstrated greater increases in the second premolars than the first
      premolars; the increases group-wise were larger in PG 2 than PG 1. However, both
      the group comparison (PG 1 versus PG 2) and the side comparison (right versus
      left) (differentiated into first and second molars) showed no statistically
      relevant differences. Visual assessment of the radiographs revealed no evidence
      of treatment-related root deviations. CONCLUSION: A highly complex system of
      forces acts on the anchoring teeth during molar distalization with the
      conventionally-anchored Pendulum K. However, the Pendulum K appliance's specific
      biomechanics make it possible to transfer the reactive forces and moments to the
      anchorage unit so that they remain within the physiological range, allowing
      uninhibited premolar root development. This also applies after completed eruption
      of the second molars, when the treatment period and hence duration of exposure to
      the active and reactive forces and moments arising during molar distalization are
      comparatively increased.

PMID- 20676816
TI  - Bonded orthodontic retainers: a comparison of initial bond strength of different
      wire-and-composite combinations.
AB  - OBJECTIVES: The aim of this in-vitro study was to evaluate initial bond strength
      in Newton (N) of two types of wires (Ortho- Flextech chain and Penta-One Coaxial
      wire 0.0215") bonded with three lingual retainer composites (FlowTain, Light Cure
      Retainer and Transbond LR). MATERIALS AND METHODS: One hundred and eighty sound,
      extracted human premolars were randomly divided into six equal groups. One of the
      two types of lingual retainer wires was bonded with one of the three types of the
      composite material in each group. Initial bond strength was measured using an
      Instron universal testing machine. We also evaluated the failure characteristics
      after failure at maximum load using an optical microscope. RESULTS: Our findings
      demonstrated that the Coaxial/Transbond LR group was statistically significantly
      stronger than the other combinations. Statistically, 0.0215" Coaxial wire
      provided significantly stronger bond strength than Ortho-Flextech chain, and when
      the three composite systems were compared, Transbond LR revealed significantly
      higher bond strength than the others. However, Transbond LR left significantly
      more resin on the enamel surface after bond failure. CONCLUSION: Significant
      differences exist between different combinations of wires and lingual retainer
      composites; however, all the wire-and-composite combinations we tested possess
      sufficient bond strength for clinical application.

PMID- 20676817
TI  - Lower bonded retainers: survival and failure rates particularly considering
      operator experience.
AB  - OBJECTIVE: The aim of this study was to retrospectively assess the frequency and
      type of lower bonded retainer failures and to analyze the possible influence of
      operator experience. PATIENTS AND METHODS: The records of 1062 patients with
      lower bonded retainers were analyzed with respect to retainer type and failure,
      timing of failure and differences among operators. RESULTS: 34.9% of all patients
      experienced retainer failure. Cuspid retainers with two bonding sites failed
      significantly less often than multiple teeth retainers with six bonding sites.
      One or more bonding sites became detached in 22.8% of the patients, 17.9% had at
      least one total retainer loss, while only 0.8% of the patients suffered from
      retainer fractures. Experienced orthodontists exhibited significantly fewer
      failures than postgraduate students. CONCLUSIONS: The present cohort presented a
      relatively high failure rate of 34.9%. Lower bonded cuspid retainers failed
      somewhat less often than 3-3 retainers. In addition less operator experience was
      likely to correlate with a higher failure rate.

PMID- 20676818
TI  - [Editorial on the main topic acetabulum revision].

PMID- 20676819
TI  - [Standardized reconstruction of acetabular bone defects using the cranial socket
      system].
AB  - OBJECTIVE: Management of primary or secondary acetabular bone loss (D'Antonio
      type I-IV ). Implantation and stable fixation using a cementless, cranially
      extended oval press-fit cup to restore painless joint function and loading
      capacity. INDICATIONS: Septic or aseptic loosening of the acetabular component
      after total hip arthroplasty. Acetabular bone loss after tumor resection. Primary
      acetabular bone defects in developmental dysplasia of the hip. CONTRAINDICATIONS:
      Persistent deep infection. Bone defects including the parts of the iliac bone
      adjoining the sacrum (fixation of the stem in the ilium is not possible any
      more). SURGICAL TECHNIQUE: Complete exposure of the acetabular defect using a
      standard approach. Removal of the loose cup. Excision of soft and granulation
      tissue from the acetabular ground and the rim. Reaming of the acetabulum with
      sequentially larger hemispheric reamers until an adequate bony bed is created for
      the insertion of the cranial socket. Eccentric cranial sockets without a
      craniolateral flap are preferable for use in type I and II defects with teardrop
      lysis mostly involving the craniolateral acetabulum, if a trihedral press-fit
      fixation can be achieved. Supplementary screw fixation through the acetabular
      ground, is possible. If a type III defect is present, the authors recommend the
      use of cranial sockets with an anatomic flap in order to increase primary
      stability by supplementary screw fixation. This is especially recommended for the
      management of deficiencies in the medial or posterior wall. If there is pelvic
      discontinuity (type IV), adequate acetabular reconstruction with primary
      stability of the component can only be achieved by a supplementary intramedullary
      structured stem fixed in the dorsal part of the ilium. POSTOPERATIVE MANAGEMENT:
      Partial loading of the operated limb with 10 kg for a period of 6-12 weeks. Then
      increased loading with 10 kg per week. Thrombosis prophylaxis until full weight
      bearing. Physiotherapy and gait training. RESULTS: A total of 50 cup revisions
      using the ESKA cranial socket system were clinically and radiologically analyzed
      with an average follow-up of 65.7+/-28.5 months (26-123 months). Defects were
      classified according to D'Antonio. There were 21 type II, 23 type III, and six
      type IV defects. The Harris Hip Score increased from 40 preoperatively to 68.3
      points postoperatively. Four patients had recurrent hip dislocation requiring
      replacement of the inlay. In four cases of aseptic loosening, the acetabular
      component had to be revised. With revision of the acetabular component as an
      endpoint, implant survival was 92% after an average of 5.4 years.

PMID- 20676820
TI  - [Exchange of acetabular cups with severe bone defects using antiprotrusion
      cages].
AB  - OBJECTIVE: Replacement of a loosened acetabular cup attended by massive bone
      defects involving both columns. Acetabular restoration and proof fixation of a
      new acetabular cup to restore a pain-free joint function. INDICATIONS: Segmental
      acetabular bone defects involving both columns (Paprosky type 3A, 3B) with
      loosened acetabular cup or a Girdlestone situation. In case of pelvic
      discontinuity (Paprosky type 4) combination with reconstructive osteosynthesis
      plates (for example, Synthes company, Bochum, Germany). CONTRAINDICATIONS: In
      cases of complete absence of the posterior and especially cranioposterior column
      combination with structural allograft reconstruction necessary. Relative:
      acetabular defects, that can be reconstructed by other, smaller implants, for
      example, press-fit acetabular cups. SURGICAL TECHNIQUE: Exposure of the
      acetabulum by a conventional approach. Removal of the loosened acetabular cup.
      Cleaning of the acetabulum with a sharp spoon. Rebuilding of the hip center with
      a reamer. Choice of the size of the antiprotrusion ring using trial implants.
      Access chiseling for the inferior implant flange into the ischium. If necessary,
      adaptation of the superior and inferior flange alignment to the individual
      anatomy by bending. Filling of bone defects with allogenic bone chips. Knocking
      in of the inferior flange into the ischium. Simultaneous knocking in of both the
      ring in the acetabulum and the superior flange at the ischium. Screwing in of
      bolts from the interior of the ring into the iliac bone in the direction of hip
      forces. Additional positioning of screws due to the superior flange into the
      iliac bone. Cementing in of a polyethylene cup in the antiprotrusion ring.
      POSTOPERATIVE MANAGEMENT: Antithrombotic prophylaxis, physical therapy, gait
      training under full weight bearing of the limb. RESULTS: 30 acetabular cup
      revisions with a new Burch-Schneider ring underwent prospective clinical and
      radiologic examination and were analyzed for an average follow-up of 20.6+/-7.8
      months (3-36 months). The Harris Hip Score increased from preoperative 46.6 to
      postoperative 75.9 points. A loosening of the cage was not recorded.

PMID- 20676821
TI  - [Reconstruction of large acetabular defects using trabecular metal augments].
AB  - OBJECTIVE: Revision of cup and reconstruction of original center of rotation.
      High primary and secondary stability. Prevention of additional bone loss.
      INDICATIONS: Osseous defects at the anterior-cranial, cranial and posterior
      cranial rim of acetabulum. Larger cavitary, medial or oval defects (Paprosky IIb
      IIIb). Segmental defects (anterior column up to half of host bone, posterior
      column up to one third of host bone). CONTRAINDICATIONS: Infection of total hip
      arthroplasty. Pelvic discontinuity (Paprosky IV). SURGICAL TECHNIQUE: Exposure of
      acetabulum and detection of defects. Complete removal of soft tissue from
      acetabulum, reaming of sclerotic bone, if necessary. Adaptation of trial augments
      to close an oval defect to a round defect and to reach an uncontained defect,
      respectively. Adaptation of trial cup. In case of sufficient stability, fixation
      of final augment with two or three screws in cranial bone stock. The screws
      should be directed to iliosacral joint. Augmentation with allogenic bone chips is
      possible in the region of wedge and acetabulum as well. Sealing of rough augment
      surface with bone cement. Implantation of cup, fixation with screws. Application
      of insert. POSTOPERATIVE MANAGEMENT: Depending on bone defects, full weight
      bearing is possible. In cases of severe bone defects, reduction of weight bearing
      to 20 kg for 6 weeks is recommended. Postoperative physiotherapy is possible in
      most cases. RESULTS: Between 2005 and 2007, 38 patients with acetabular defects
      type IIIa und IIIb according to Paprosky underwent reconstruction using the TMT
      system (Trabecular Metal Technology). After 25 months, a significant functional
      improvement was seen in all patients. The Merle d'Aubigne Score increased from 6
      points preoperatively to 13 points postoperatively, the Harris Hip Score from 29
      to 78 points. Two revisions were necessary because of loosening or migration of
      the cup.

PMID- 20676822
TI  - [Treatment of the complex intraarticular fracture of the distal humerus with the
      latitude elbow prosthesis].
AB  - OBJECTIVE: Therapy of comminuted intraarticular distal humerus fractures in
      elderly patients with primary total elbow arthroplasty to achieve stable and
      painless function. Use of "third-generation" elbow prosthesis with the following
      options:--linked total elbow arthroplasty,--unlinked total elbow arthroplasty,-
      either with or without radial head replacement,--hemiarthroplasty. INDICATIONS:
      Comminuted intraarticular distal humerus fractures with poor bone quality, in
      which stable osteosynthesis is impossible. Failure of internal fixation without
      the technical possibility of revision osteosynthesis. Posttraumatic
      osteoarthritis or rheumatoid arthritis. CONTRAINDICATIONS: Open fractures
      (Gustilo-Anderson type II or III) or contaminated wounds should not initially be
      treated with total elbow arthroplasty. Prosthetic replacement may be considered
      after consolidation of the soft tissue. Low compliance, high functional demands.
      Paralysis of the biceps muscle. SURGICAL TECHNIQUE: Supine positioning of the
      patient. Surgical approach after Bryan-Morrey. Anterior transposition of the
      ulnar nerve. Preparation of the insertion of the triceps at the distal humerus,
      capsule and proximal ulna. Reflection of the triceps in continuity with the ulnar
      periosteum and the forearm fascia. Attempt at reconstruction of the epicondyles
      to achieve ligamentary stability and to implant an unlinked prosthesis. If this
      is technically not possible, the prosthesis is linked at the end of the
      operation. Removal of the distal humerus fragments. Determination of the
      prosthesis size. Detection of the extension-flexion axis. Opening of the humeral
      intramedullary canal. Determination of the offset. Preparation of the humeral
      prosthesis repository. Placement of the trial prosthesis. Potential implantation
      of a hemiprosthesis, if radial head, proximal ulna and ligaments are unaffected.
      Otherwise preparation of the ulnar prosthesis repository. If the radial head is
      unaffected, it can be preserved. Otherwise it has to be resected and preferably
      replaced. Placement of the ulnar and radial trial prosthesis. After correct trial
      reposition cementing of all definitive prosthesis components with attachment of a
      cortical bone graft behind the ventral flange of the humeral component. If there
      is no sufficient stability at the end of the operation, the prosthesis must be
      linked by insertion of the ulnar cap. POSTOPERATIVE MANAGEMENT: Postoperative
      anterior upper-arm splint in full extension. Active motion. No active extension
      for 6 weeks. Avoidance of single-event weight lifting>5 kg, no repetitive weight
      lifting>1 kg, and no forced elbow movements, e.g., racquet sports. RESULTS: 15
      Latitude elbow prostheses were implanted in 2007 and 2008 at the Department of
      Trauma Surgery of the University Hospital Mainz, Germany, due to the following
      indications: fractures (n=7), pseudarthrosis (n=4), posttraumatic osteoarthritis
      (n=3), and rheumatoid arthritis (n=1). Six hemiprostheses, two unlinked and seven
      linked prostheses were implanted. The mean age of patients was 67 years (31-88
      years). For the treatment of acute fractures, the indication was made only in
      elderly patients. The mean age was 77 years (66-88 years). Eleven of these 15
      patients were reexamined after 13.5 months (6-23 months). The mean extension
      deficit was 15 degrees (0-30 degrees), the mean flexion 119 degrees (95-140
      degrees). The mean pronation was 78 degrees (60-90 degrees), the mean supination
      79 degrees (50-90 degrees). According to the Mayo Elbow Performance Score, three
      patients achieved an excellent, seven a good, and one a fair result. The mean
      Mayo Score was 89.2 (74-100). The mean DASH (Disabilities of the Arm, Shoulder
      and Hand) Score was 8.4 (0-28).

PMID- 20676823
TI  - [Laminoplasty].
AB  - OBJECTIVE: The aims of laminoplasty are to expand the spinal canal, to secure
      spinal stability, and to preserve the protective function of the spine.
      Preservation of mobility is also a goal of this procedure for multiple-level
      involvement. INDICATIONS: Multisegmental spondylotic myelopathy with a relatively
      narrow spinal canal (anteroposterior spinal canal diameter<13 mm).
      CONTRAINDICATIONS: Spinal instability. Kyphotic cervical spine. SURGICAL
      TECHNIQUE: Prone positioning of the patient. Three-point pin fixation device such
      as Mayfield tongs to secure the head. Midline posterior approach to the spine.
      Exposure of the laminae and the spinous processes. Opening and expanding of the
      spinal canal, decompression of the spinal cord. Fixation of the laminae with bone
      and/or implants. POSTOPERATIVE MANAGEMENT: Cervical collar for 3-4 weeks.
      RESULTS: Long-term investigations have shown neurological improvement in 57%, a
      decrease of range of motion in 36%, and a slight reduction of lordosis without
      clinical relevance.

PMID- 20676824
TI  - [Imageless computer navigation of hip resurfacing arthroplasty].
AB  - OBJECTIVE: Precise implantation of hip resurfacing arthroplasty by imageless
      computer navigation. Hence a malalignment of the femoral component, leading to
      early loss of the implant, can safely be avoided. INDICATIONS: Coxarthrosis in
      patients with normal bone mineral density; only minor deformity of the femoral
      head that enables milling around the femoral neck without notching.
      CONTRAINDICATIONS: Osteoporosis; large necrosis of the femoral head; metal
      allergy; small acetabular seat and corresponding wide femoral neck, leading to
      needless acetabular bone loss; pregnancy, lactation. SURGICAL TECHNIQUE: Hip
      joint exposure by a standard surgical approach, bicortical placement of a Schanz
      screw for the navigation array in the lesser trochanter. Referencing of the
      epicondyles, the four planes around the femoral neck and head by use of the
      navigation pointer. Planning of the desired implant position on the touchscreen
      of the navigation device; a guide wire is inserted into the femoral head and neck
      using the navigated drill guide; navigated depth drilling is performed. The
      femoral head is milled using the standard instruments. The acetabular bone stock
      is prepared with the conventional instrumentation; high-viscosity cement is
      finger-packed on the reamed head and the femoral component is inserted. Hammer
      blows should be avoided to prevent microfractures. Verification of the implant
      position by the navigation device; displacement of the Schanz screw; joint
      reposition and closure of the wound. POSTOPERATIVE MANAGEMENT: Standard
      postoperative management after hip arthroplasty. RESULTS: The comparison of 40
      navigated and 32 conventionally implanted ASR prostheses resulted in a
      significant reduction of outliers by use of computer navigation (navigated
      procedures: one outlier, conventional procedure: nine outliers; p<0.001).
      Accuracy of the navigation device was tested by analysis of planned and verified
      implant position: CCD angle accuracy was 1 degrees , antetorsion accuracy was 1
      degrees , and offset accuracy was 1.5 mm. An ongoing computed tomography-based
      anatomic study proved a varus-valgus accuracy of the navigation device of 1
      degrees .

PMID- 20676825
TI  - [The medial closed-wedge osteotomy of the distal femur for the treatment of
      unicompartmental lateral osteoarthritis of the knee].
AB  - OBJECTIVE: Shifting of the mechanical axis from the lateral to the medial
      compartment in patients with lateral osteoarthritis in combination with valgus
      deformity. INDICATIONS: Osteoarthritis of the lateral compartment in combination
      with valgus deformity of the (distal) femur. Posttraumatic and congenital valgus
      deformities of the (distal) femur. CONTRAINDICATIONS: Osteoarthritis of the
      medial compartment (>or=grade 3 on Outerbridge Scale). Total loss of the medial
      meniscus. Acute or chronic infections. Rheumatoid arthritis. Heavy smoking.
      Extension or flexion deficit>20 degrees. Poor soft-tissue conditions on site of
      surgery. SURGICAL TECHNIQUE: Optional: arthroscopy before osteotomy. Anteromedial
      skin incision, subvastus approach with blunt preparation around the vastus
      medialis muscle and separation of this muscle from the intermuscular septum. The
      posterior osteotomy is marked with Kirschner wires (OGD [osteotomy guiding
      device], Synthes, Switzerland, can be used optionally). The biplanar cut is
      marked on the bone with an electrocautery device. The bone cuts start with the
      posterior incomplete osteotomy, followed by the anterior biplanar cut. After
      finishing the osteotomy (three bone cuts!), the bone wedge can be removed.
      Closing the osteotomy should start very gently as a plastic deformation of the
      bone. A radiologic control of the leg alignment and the mechanical axis is
      achieved with an alignment rod (Synthes, Switzerland). The plate should be
      inserted under the vastus medialis muscle. It is very important, that the surgeon
      controls the correct anteromedial position of the plate at the distal femur
      (right and left version of the implant). Fixation of the plate with locking
      screws distally. Positioning of a lag screw in the dynamic hole directly above
      the osteotomy. Insertion of monocortical screws in the three remaining holes
      proximal of the lag screw. Finally, the lag screw is changed to a self-tapping
      bicortical locking head screw. X-ray control, wound closure. POSTOPERATIVE
      MANAGEMENT: Elastic bandage of the leg up to the thigh in the operating room.
      Change of the dressing on day 1 after surgery. Ice treatment. Walking on crutches
      starting day 1 after surgery. Physiotherapy and manual lymph drainage starting on
      day 1 after surgery. Partial weight bearing for the first 4-6 weeks after
      surgery. Suture removal after 10-12 days. X-ray control on day 3 and 6 weeks
      after surgery. Discharge possible, if wounds are dry (day 4-7). RESULTS: Between
      January 2005 and October 2008, 60 patients were treated with medial closed-wedge
      osteotomy of the distal femur (since 11/2006 only with biplanar osteotomy
      technique) at the Department of Trauma and Reconstructive Surgery,
      Diakoniekrankenhaus Henriettenstiftung Hannover, Germany. The average wedge size
      was 7.6 mm (4-13 mm). The mean age was 39.7 years (17-79 years). The patients had
      had 2.3 previous surgeries. The mean follow- up was 21 months (3-45 months).
      Freiling D, et al. Biplanare Osteotomie bei unikompartimentaler lateraler
      Kniegelenkarthrose Flexion was 126 degrees (95-140 degrees) preoperatively, and
      128 degrees (105-140 degrees) postoperatively. 25 patients had at least 5 degrees
      extension deficit (5-15 degrees) before surgery, whereas ten patient did not
      reach the full extension at follow-up examination. The Tegner Activity Score
      increased from 2.8 (1-4) preoperatively to 5.6 (2-9) postoperatively, in IKDC
      (International Knee Documentation Committee) Score, 18 patients reached grade A,
      27 grade B, nine grade C, and six grade D. The visual analog scale (VAS) score
      decreased from 6.8 (8-2) preoperatively to 3.1 (0-7) postoperatively. Seven
      patients had revision surgery (three times delayed union/nonunion of the
      osteotomy, one superficial and one deep infection, one hematoma, one fracture
      [proximal of the internal plate fixator] after a fall).

PMID- 20676826
TI  - [Release of the lateral plantar nerve in case of entrapment].
AB  - OBJECTIVE: Reduction of heel pain by neurolysis of the lateral plantar nerve.
      Indications Contraindications Surgical Technique Postoperative Management Results
      INDICATIONS: Heel pain due to an entrapment of the lateral plantar nerve.
      CONTRAINDICATIONS: Acute inflammatory alterations in the foot. Skin laceration at
      the medial hindfoot. Relative: heel pain, which could not be assigned to a
      distinct diagnosis. Relative: flatfoot deformity with hindfoot valgus. SURGICAL
      TECHNIQUE: Regional anesthesia. Supine position. Tourniquet. Curved skin incision
      behind the medial malleolus to the medioplantar aspect of the heel. Incision of
      the flexor retinaculum and careful dissection of the tibial nerve, until the
      medial and lateral plantar nerves can be clearly identified. Stepwise
      decompression of the lateral plantar nerve along its course to the medial aspect
      of the heel. Exposure of the first branch of the lateral plantar nerve (Baxter's
      nerve) by dissection of the fascia overlying the quadratus plantae muscle and the
      flexor digitorum brevis muscle. Release of the tourniquet and hemostasis. Wound
      closure in layers. Below-knee splint in neutral position of the ankle.
      POSTOPERATIVE MANAGEMENT: Elevation of the concerned leg. Mobilization without
      weight bearing during the first 5 days. Stepwise increased weight bearing
      according to the pain level. Soft insoles for 12 weeks. No running or jumping for
      12 weeks. RESULTS: From 2006 to 2008, twelve patients (ten women, two men) were
      treated with a neurolysis of the lateral plantar nerve. In nine patients, the
      diagnosis was confirmed neurologically; in three patients, the authors decided to
      perform the nerve decompression due to clinical findings. The patients were
      followed up clinically (mean follow-up 15 months) and were asked to estimate
      their pain level with the visual analog scale (VAS). There were no postoperative
      complications. One patient developed a complex regional pain syndrome. Pain level
      decreased significantly within 6 weeks (VAS preoperatively 7.9; VAS
      postoperatively 3.8) and showed a further pain reduction to VAS 2.1 after 9
      months. Two patients complained of recurrent symptoms after a mean of 11 months.
      In these patients, the initial diagnosis could not be confirmed by
      electrophysiological measurements.

PMID- 20676827
TI  - Conceptual change, crucial experiments and auxiliary hypotheses. A theoretical
      contribution.
AB  - Theories about conceptual change have been generally related to historical and
      philosophical analysis of science. Yet, there is still much debate on how ideas
      coming from the history of science and their implications can be applied in this
      field. Our study intends to investigate the complex structure of conceptual
      change, by making use of some particularly representative features of the History
      and Philosophy of science, while considering the structure of so-called crucial
      experiments and the specific role of implicit hypotheses. Due to their historical
      importance and logical reasoning aspects, examining these issues may contribute
      to understand how conceptual change may take place.

PMID- 20676828
TI  - Methotrexate-related Epstein-Barr Virus (EBV)-associated lymphoproliferative
      disorder--so-called "Hodgkin-like lesion"--of the oral cavity in a patient with
      rheumatoid arthritis.
AB  - Patients affected by autoimmune diseases (rheumatoid arthritis, psoriasis,
      dermatomyositis) who are treated with methotrexate (MTX) sometimes develop
      lymphoproliferative disorders (LPDs). In approximately 40% of reported cases, the
      affected sites have been extranodal, and have included the gastrointestinal
      tract, skin, lung, kidney, and soft tissues. However, MTX-associated LPD (MTX
      LPD) is extremely rare in the oral cavity. Here we report a 69-year-old Japanese
      woman with rheumatoid arthritis (RA) who developed MTX-LPD resembling Hodgkin's
      disease--so-called "Hodgkin-like lesion"--in the left upper jaw.
      Histopathologically, large atypical lymphoid cells including Hodgkin or Reed
      Sternberg-like cells were found to have infiltrated into granulation tissue in
      the ulcerative oral mucosa. Immunohistochemistry showed that the large atypical
      cells were positive for CD20, CD30 and Epstein-Barr virus (EBV)-latent infection
      membrane protein-1 (LMP-1) and negative for CD15. EBV was detected by in situ
      hybridization (ISH) with EBV-encoded small RNA (EBER), and polymerase chain
      reaction (PCR) for LMP-1 and EBNA-2 in material taken from the formalin-fixed,
      paraffin-embedded specimen. To our knowledge, this is the first reported case of
      MTX-related EBV-associated LPD (MTX-EBVLPD), "Hodgkin-like lesion", of the oral
      cavity in a patient with RA.

PMID- 20676829
TI  - Clinical-pathological conference: case 3.

PMID- 20676830
TI  - Clinical-pathological conference: case 6.

PMID- 20676831
TI  - Clinical-pathological conference: case 4.

PMID- 20676832
TI  - Clinical-pathological conference: case 5.

PMID- 20676833
TI  - Clinical-pathological conference: case 2.

PMID- 20676834
TI  - Manual versus nonmanual thrombectomy in primary and rescue percutaneous coronary
      angioplasty.
AB  - Although many thrombectomy devices have been tested in ST-segment elevation acute
      myocardial infarction (STEMI), there are no comparative data on safety or
      effectiveness in thrombectomy or ST-segment resolution. This study compares
      manual versus nonmanual thrombectomy devices in patients undergoing primary or
      rescue percutaneous coronary intervention in a tertiary care center. We
      identified 232 consecutive patients with STEMI and time from symptom onset to
      emergency room contact of < or = 12 h undergoing percutaneous coronary
      intervention with coronary thrombectomy devices. Primary end point was ST-segment
      resolution of > or = 70%. Several angiographic, procedural and clinical secondary
      end points were also evaluated. The manual thrombectomy group included 110
      patients and the nonmanual group 122 patients. Both groups were similar in their
      clinical characteristics. The primary end point occurred with similar frequency
      in patients treated with manual versus nonmanual thrombectomy (67.9% vs 60.0%, P
      = 0.216). No significant differences were found in the two groups with regard to
      procedural complications, angiographic reperfusion parameters, in-hospital major
      adverse cardiac events, or infarct size, whereas manual thrombectomy was
      associated with a better left ventricle ejection fraction at discharge.
      Furthermore, treatment with a manual thrombectomy device was associated with
      significantly shorter procedural times (69 min vs 95 min, P < 0.001) and lower
      procedural costs (2981 euros vs 7505 euros, P < 0.001). The use of manual
      thrombus-aspiration catheters appeared equivalent to nonmanual thrombectomy
      devices in the setting of primary or rescue percutaneous intervention in terms of
      clinical efficacy, and led to shorter procedures and cost savings.

PMID- 20676835
TI  - Circulating soluble CD40 ligand mediates the interaction between neutrophils and
      platelets in acute coronary syndrome.
AB  - Following plaque rupture, activated platelet will induce subsequent inflammatory
      process including neutrophil recruitment. In vitro study demonstrated an
      interaction between neutrophils and platelets via a mechanism involving CD40-CD40
      ligand. However, whether this mechanism exists in the clinical setting remains
      unknown. Fifty-four patients with acute myocardial infarction (AMI) and 25 with
      unstable angina of pain onset of < or = 24 h were enrolled consecutively. Acute
      myocardial infarction was diagnosed from three diagnostic criteria, i.e., anginal
      pain, electrocardiogram ST-T changes, and cardiac enzyme elevation. Unstable
      angina was diagnosed in patients without elevated cardiac enzymes. Peripheral
      venous blood was drawn at admission for routine blood count and soluble CD40
      ligand (sCD40L) measurement. Neutrophil count was determined by an automated
      blood cell counter. Circulating sCD40L was measured using a standard enzyme
      linked immunosorbent assay. Neutrophil count was significantly higher in AMI as
      compared with unstable angina (P < 0.001), whereas circulating sCD40L did not
      significantly differ. Despite marked elevation, no correlation was observed
      between neutrophil count and circulating sCD40L in AMI. Interestingly, we
      observed a strong and positive significant correlation between neutrophil count
      and circulating sCD40L level (r = 0.607, P = 0.002) in unstable angina.
      Circulating sCD40L is associated with neutrophil count and may mediate
      interaction between neutrophils and platelets in acute coronary syndrome,
      particularly in unstable angina.

PMID- 20676837
TI  - Characterization of patients with bleeding complications who are at increased
      risk of death after percutaneous coronary intervention.
AB  - Bleeding complications in patients undergoing percutaneous coronary interventions
      (PCIs) are associated with increased risk of subsequent mortality. We undertook
      this study to characterize the subset of patients with bleeding complications who
      are at an increased risk of death within the first year after a PCI procedure.
      The study included 331 patients with bleeding complications among 9 954 patients
      who underwent PCI. The primary outcome analysis was 1-year mortality. Within the
      first year following PCI there were 39 deaths among 331 patients (11.8%), with
      bleeding complications and 240 deaths among 9 623 patients without bleeding
      complications (Kaplan-Meier estimates of 1-year mortality; 11.8% vs 2.5%, odds
      ratio 5.09, 95% confidence interval 3.76-6.90, P < 0.001). Time to death (median
      [25th-75th percentiles]) was 38.5 [7.2-125.9] days in patients with bleeding
      complications vs 137.1 [68.3-234.0] days in patients without bleeding
      complications (P < 0.001). Compared with survivors (n = 292), nonsurvivors (n =
      39) had a significantly more adverse risk profile. The Cox proportional hazards
      model identified the elevated troponin level as the only independent correlate of
      1-year mortality (hazard ratio = 2.35, 95% confidence interval 1.04-5.31, P =
      0.039). In conclusion, patients with peri-PCI bleeding complications who die have
      a more adverse cardiovascular risk profile than patients with bleeding
      complications who survive the first year after PCI. Patients with bleeding
      complications and an elevated troponin level are at high risk of death within the
      first year following PCI. The majority of deaths in patients with peri-PCI
      bleeding occur within the first 3 months after PCI procedure.

PMID- 20676836
TI  - Simvastatin-induced changes in circulating oxidized low-density lipoprotein in
      different types of dyslipidemia.
AB  - Beyond lowering lipid levels, 3-hydroxy-3-methyl glutaryl coenzyme A reductase
      inhibitors (statins) have been shown to possess antioxidant properties, which may
      explain some of their beneficial effects in reducing atherosclerosis. We sought
      to determine whether circulating oxidized low-density lipoprotein (ox-LDL) levels
      differ between subjects with isolated hypercholesterolemia and combined
      hyperlipidemia, as well as the effect of simvastatin on circulating ox-LDL
      according to the type of dyslipidemia. Twenty-five subjects with total
      cholesterol >200 mg/dl and triglycerides <150 mg/dl, and 22 subjects with total
      cholesterol >200 mg/dl and triglycerides >150 mg/dl were treated with 40 mg
      simvastatin daily for 3 months. Serum lipids, C-reactive protein, fibrinogen, ox
      LDL, and free radicals were measured at baseline and after 3 months of treatment.
      In both groups studied, simvastatin significantly improved lipids, and reduced C
      reactive protein and fibrinogen levels. Free radicals were significantly reduced
      only in subjects with hypercholesterolemia. Subjects with combined hyperlipidemia
      had significantly higher baseline levels of ox-LDL compared to those with
      hypercholesterolemia (64.6 U/l vs 53.5 U/l, P = 0.03). Ox-LDL levels were reduced
      by 12% in subjects with hypercholesterolemia (P = 0.03) and by 26% in subjects
      with combined hyperlipidemia (P = 0.001) after simvastatin treatment. In
      conclusion, subjects with combined hyperlipidemia have increased levels of
      circulating ox-LDL compared to subjects with isolated hypercholesterolemia.
      Simvastatin significantly reduced circulating ox-LDL in both groups, but whether
      this reduction is related to clinical outcomes remains to be shown.

PMID- 20676838
TI  - Noninvasive assessment of myocardial damage after acute anterior myocardial
      infarction: myocardial blush grade in conjunction with analysis of coronary flow
      pattern.
AB  - In patients with acute myocardial infarction (AMI), both myocardial blush grade
      (MBG) and coronary flow pattern obtained by transthoracic Doppler
      echocardiography (TTDE) have limitations in assessing myocardial viability.
      Accordingly, we assessed the usefulness of combination of MBG and TTDE in
      predicting myocardial damage following AMI. A total of 45 patients with anterior
      AMI were enrolled. Myocardial blush grade and coronary flow velocity (CFV),
      diastolic deceleration time (DDT), and coronary flow velocity reserve (CFVR) were
      measured immediately after reperfusion. The regional wall motion score index
      (RWMSI) was measured at 14 days after onset. The MBG was normal in 12 patients.
      The RWMSI was significantly better in the patients with normal than with abnormal
      MBG (1.65 +/- 0.29 vs 2.03 +/- 0.46, P < 0.05). Among the coronary flow indices,
      only DDT showed the significant correlation with RWMSI (P < 0.05, r = -0.44). To
      predict RWMSI > or = 2, sensitivity and positive predictive value (PPV) were
      86.3% and 65.5% in DDT alone, 90.9% and 65.5% in MBG alone, respectively.
      Predictable value was enhanced by the combination with DDT and MBG, with
      sensitivity of 100% and PPV of 70.8% in 31 patients whose results of both
      corresponded. MBG in conjunction with TTDE was useful in predicting myocardial
      damage after anterior AMI.

PMID- 20676839
TI  - Cardio-renal interaction: impact of renal function and anemia on the outcome of
      chronic heart failure.
AB  - The purpose of this study is to investigate the effects of renal function and
      anemia on the outcome of chronic heart failure (CHF). We targeted 711 consecutive
      patients who were hospitalized at the Division of Cardiology of Fujita Health
      University Hospital during a 5-year period. The subjects were divided into four
      groups according to their estimated glomerular filtration rate (e-GFR) calculated
      using the Modification of Diet in Renal Disease (MDRD) formula. Intergroup
      comparisons were conducted for underlying heart diseases, clinical findings at
      the time of hospitalization, treatment, and outcome. Moreover, the patients were
      divided into two groups according to their serum hemoglobin concentration at the
      time of hospitalization, using 12.0 g/dl as the dividing point, to study the
      effects of anemia on the outcome. In the group with decreased renal function, the
      average age was higher, and ischemic heart disease and associated conditions such
      as hypertension and diabetes mellitus were observed in most of the patients. In
      addition, the rate of anemia development and the plasma B-type natriuretic
      peptide concentration were also high. The greater the deterioration in renal
      function, the poorer the outcome became (P < 0.0001). Chronic heart failure
      complicated by anemia showed an especially poor outcome (P < 0.0001). As this
      study showed that renal function and anemia significantly affected the outcome of
      CHF, it is clear that the preservation of renal function and the management of
      anemia are important in addition to the conventional treatments for CHF.

PMID- 20676840
TI  - Noninvasive assessment of acute cardiopulmonary effects of an oral single dose of
      sildenafil in patients with idiopathic pulmonary hypertension.
AB  - We aimed to assess the acute cardiopulmonary effects of a 100-mg oral single dose
      of sildenafil in patients with idiopathic pulmonary hypertension (IPAH) using a
      well-validated but less-used noninvasive echocardiographic method for the
      measurement of both systolic and diastolic pulmonary artery pressure (PAP), by
      tricuspid regurgitation (TR) velocity curve analysis. We studied 12 consecutive
      patients with IPAH (10 patients with New York Heart Association functional class
      III, and 2 patients with functional class II). A 100-mg oral single dose of
      sildenafil was added to previous medications of all patients and its immediate
      effects were evaluated 1, 5, and 12 h after treatment. Using paired analysis,
      administration of a 100-mg oral single dose of sildenafil led to a significant
      reduction in mean PAP and a remarkable increase in pulmonary acceleration time
      (PAT) 1 h after treatment (P = 0.000; 95% confidence interval [CI] 18.99-26.00
      and P = 0.005; 95% CI -12.89 to -2.95, respectively). In addition, although the
      right heart dimensions (right atrium and right ventricle) showed a trend toward
      improvement, the differences were not statistically significant (P = 0.13 and P =
      0.08, respectively). Our results demonstrated that Doppler examination of TR
      alone can be easily used for the estimate of systolic and diastolic PAP in
      patients with IPAH. This study also shows that sildenafil is the only drug given
      orally that can evaluate the vasodilatory capacity of the pulmonary vascular bed
      in patients with IPAH, with promising effects on mPAP and PAT in these patients.

PMID- 20676841
TI  - Fluctuation of serum vitamin E (alpha-tocopherol) concentrations during
      exacerbation and remission phases in patients with chronic fatigue syndrome.
AB  - The etiology of chronic fatigue syndrome remains unknown. Oxidative stress may be
      involved in its pathogenesis. Vitamin E is a major endogenous lipid-soluble
      antioxidative substance, and is consumed during the lipid peroxidation process.
      We studied a population comprising 27 patients with chronic fatigue syndrome (10
      men and 17 women, 29 +/- 6 years of age) and 27 age- and sex-matched control
      subjects. Serum vitamin E (alpha-tocopherol) concentrations were determined and
      expressed as mg/g total lipids (total cholesterol and triglyceride) to evaluate
      oxidative stress. Serum alpha-tocopherol concentrations (mg/g lipids) were
      significantly (P < 0.001) lower in the patients with chronic fatigue syndrome
      (2.81 +/- 0.73) than in the control subjects (3.88 +/- 0.65). The patients with
      chronic fatigue syndrome were re-examined during a follow-up interval. After 8 +/
      2 months, 16 patients exhibited a status that warranted re-examination during
      remission of the symptoms at a regular visit to our hospital (Group 1), while the
      remaining 11 did not (Group 2). The serum alpha-tocopherol levels were
      significantly elevated during remission as compared with those at baseline in
      Group 1 (2.71 +/- 0.62 --> 3.24 +/- 0.83, P < 0.001). The levels did not
      significantly change after the interval in Group 2 (2.97 +/- 0.86 --> 2.85 +/-
      0.73, not significant). In conclusion, serum alpha-tocopherol concentrations were
      significantly lower in the patients with chronic fatigue syndrome as compared
      with the control subjects, suggesting increased oxidative stress in the former.
      The low level of serum alpha-tocopherol was ameliorated during the remission
      phase as compared with the exacerbation phase in the patients with chronic
      fatigue syndrome, suggesting that increased oxidative stress may be involved in
      the pathogenesis of chronic fatigue syndrome and might also be directly related
      to the severity of the symptoms of chronic fatigue syndrome.

PMID- 20676842
TI  - Different angiogenesis effect of mini-TyrRS/mini-TrpRS by systemic administration
      of modified siRNAs in rats with acute myocardial infarction.
AB  - We aimed to clarify the different angiogenesis effects of mini-tyrosyl-tRNA
      synthetase (TyrRS)/minitryptophanyl-tRNA synthetase (TrpRS) in rodent primates
      with acute myocardial infarction, by delivering small interfering RNAs (siRNAs)
      systemically in a liposomal formulation. Left coronary artery ligation was used
      to establish the model of acute myocardial infarction in rats; mini-TyrRS/mini
      TrpRS-specific siRNAs were encapsulated in stable nucleic acid lipid particles
      (SNALP), and administered by intravenous injection to rats. Rats were divided
      into four experiment groups: sham operated group (no left anterior descending
      artery [LAD] occlusion); negative control group (LAD occlusion + saline
      injection); mock transfection group (LAD occlusion + mock transfected injection);
      experiment group (LAD occlusion + mini-TyrRS/mini-TrpRS-specific siRNAs
      injection). Silencing efficiency was assayed by Western blotting. To determine
      whether mini-TyrRS/mini-TrpRS affected the angiogenesis activity of rats with
      myocardial infarction, we measured the myocardial infarction size by TTC
      staining, and the capillary density using immunohistochemistry staining, to
      investigate the expression of factor VIII. The myocardial infarction size and the
      capillary density of mini-TyrRS-siRNA group were respectively 18.89% and 8.64/0.1
      mm(2) 1 month after ligation, while in the mini-TrpRS-siRNA group these values
      were 7.33% and 17.32/0.1 mm(2), significantly different compared with the mock
      transfection group (14.19%; 13.56/0.1 mm(2)) and negative control group (14.28%;
      13.89/0.1 mm(2)), P < 0.05. There were no significant changes between the mock
      transfection group and the negative control group, P > 0.05. These results
      indicated that angiogenesis is either stimulated by mini-TyrRS or inhibited by
      mini-TrpRS in rat models with acute myocardial infarction.

PMID- 20676843
TI  - Fatigue life analysis and experimental verification of coronary stent.
AB  - A computational and experimental method on biomechanics of stent is presented to
      analyze the stress distribution of different phases and evaluate the fatigue life
      according to Goodman criteria. As a result, the maximum stress and alternating
      stress were always located at the curvature area of rings, the fatigue bands in
      the experiment also verified the computation rationality. Matching between the
      numerical simulation and experimental results was satisfactory, which proved that
      the finite element analysis could provide theoretical evidence and help design
      and optimize the stent structure.

PMID- 20676844
TI  - Acute amiodarone promotes drift and early termination of spiral wave re-entry.
AB  - Intravenous application of amiodarone is commonly used in the treatment of life
      threatening arrhythmias, but the underlying mechanism is not fully understood.
      The purpose of the present study is to investigate the acute effects of
      amiodarone on spiral wave (SW) re-entry, the primary organization machinery of
      ventricular tachycardia/fibrillation (VT/VF), in comparison with lidocaine. A two
      dimensional ventricular myocardial layer was obtained from 24 Langendorff
      perfused rabbit hearts, and epicardial excitations were analyzed by high
      resolution optical mapping. During basic stimulation, amiodarone (5 microM)
      caused prolongation of action potential duration (APD) by 5.6%-9.1%, whereas
      lidocaine (15 microM) caused APD shortening by 5.0%-6.4%. Amiodarone and
      lidocaine reduced conduction velocity similarly. Ventricular tachycardias induced
      by DC stimulation in the presence of amiodarone were of shorter duration
      (sustained-VTs >30 s/total VTs: 2/58, amiodarone vs 13/52, control), whereas
      those with lidocaine were of longer duration (22/73, lidocaine vs 14/58,
      control). Amiodarone caused prolongation of VT cycle length and destabilization
      of SW re-entry, which is characterized by marked prolongation of functional block
      lines, frequent wavefront-tail interactions near the rotation center, and
      considerable drift, leading to its early annihilation via collision with
      anatomical boundaries. Spiral wave re-entry in the presence of lidocaine was more
      stabilized than in control. In the anisotropic ventricular myocardium, amiodarone
      destabilizes SW re-entry facilitating its early termination. Lidocaine, in
      contrast, stabilizes SW re-entry resulting in its persistence.

PMID- 20676845
TI  - Role of substance P in viral myocarditis in mice.
AB  - Substance P (SP) is widely expressed in the central nervous system and in
      peripheral tissues such as myocardial nerves. We examined SP in viral myocarditis
      in mice induced by encephalomyocarditis virus (EMCV). Localization of SP in the
      hearts was examined immunohistochemically, and concentrations of SP in hearts and
      sera were measured by enzyme immunoassay. Substance P levels and density of SP
      containing cells in murine hearts on day 6 after EMCV inoculation were decreased
      compared with those in normal controls. There was a negative correlation between
      SP levels in the hearts and ratio of heart weight to body weight of the mice at 6
      days. Circulating SP levels were decreased in mice on day 6 after EMCV
      inoculation, and further decreased on day 14. Substance P in hearts and sera is
      decreased in viral myocarditis in mice, suggesting that SP may play a role in the
      pathogenesis of viral myocarditis, and that interaction of the neuropeptide
      nervous system and mast-cell immune system is important in the pathogenesis of
      viral myocarditis.

PMID- 20676846
TI  - Surgical correction of isolated unilateral absence of right pulmonary artery.
AB  - A 2-year-old girl with isolated unilateral absence of right pulmonary artery is
      described. Catheterization at 5 months demonstrated hypoplastic right pulmonary
      artery by pulmonary venous wedge angiography, and the patient underwent right
      Blalock-Taussig shunt and angioplasty of right pulmonary artery with autologous
      pericardial roll as an initial step. At 2 years, she underwent anastomosis of
      right pulmonary artery to main pulmonary artery with an autologous pericardial
      tube. Postoperative computed tomography showed a patent reconstructed right
      pulmonary artery.

PMID- 20676847
TI  - Transcatheter embolization of a huge renal arteriovenous fistula with Amplatzer
      Vascular Plug.
AB  - A large renal arteriovenous fistula (RAF) may lead to heart failure, renal
      insufficiency, hematuria, and progressive increase in size of renal vessels. Here
      we present the case of a 67-year-old man with a huge left RAF, who suffered from
      exertional dyspnea, nocturnal orthopnea, and impaired renal function. The left
      renal vein and inferior vena cava were dilated to 4 cm. An Amplatzer Vascular
      Plug with the largest size of 30 mm in disk diameter was deployed to block the
      fistula, with balloons inflated at renal artery and vein in advance, to reduce
      the renal flow in order to prevent plug migration. The decrease of shunt flow
      after embolization was suboptimal. However, dyspnea ameliorated, which was
      associated with decreased cardiac murmur, subsided abdominal bruit, normalization
      of the lowered diastolic pressure, and better renal function. In addition, more
      microcoils can be applied, using the lodged plug as a framework, to achieve the
      best clinical improvement.

PMID- 20676848
TI  - Successful percutaneous aortic valve implantation via a stenotic left subclavian
      artery access.
AB  - Severe aortic valve stenosis may be tackled with percutaneous aortic valve
      replacement instead of surgical replacement. At present, two CE marked prosthetic
      valves are available. The CoreValve ReValving System is primarily designed to be
      introduced transfemorally, while implantation via subclavian arteries has been
      described in cases of unsuitable femoral access. However, this route has been
      used when subclavian artery is free of disease. In this case report we describe a
      successful CoreValve ReValving System implantation via a diseased and tortuous
      left subclavian artery after predilatation balloon angioplasty. The prosthesis
      was then advanced in the native aortic valve, deployed, and successfully
      implanted. Techniques and manipulations are provided.

PMID- 20676849
TI  - The happy marriage of surgery and science/technology would lead to prosperous
      surgical development towards the year 2050.

PMID- 20676850
TI  - Preventing recurrence of spontaneous pneumothorax after thoracoscopic surgery: a
      review of recent results.
AB  - Spontaneous pneumothorax (SP) is now commonly treated with thoracoscopic surgery,
      which is associated with less pain and a shorter hospital stay than thoracotomy;
      however, in its initial stages, thoracoscopic stapled bullectomy resulted in an
      unexpectedly high incidence of postoperative SP recurrence. Thus, new
      thoracoscopic procedures, designed to be performed in addition to stapled
      bullectomy, were developed, which resulted in a gradual decline in the
      postoperative recurrence rate. We review the recent literature on SP recurrence
      after thoracoscopic surgery with these other surgical procedures. Pleurectomy and
      pleural abrasion have been performed for a long time with low recurrence rates;
      however, they cause the lung to adhere to the parietal pleura, often resulting in
      complications such as postoperative bleeding. Other surgical procedures that may
      be recommended to minimize the risk of recurrence are reinforcement of the staple
      lines using fleece-coated glue or an absorbable sheet. These procedures are now
      considered to be the thoracoscopic treatment of choice for SP.

PMID- 20676851
TI  - Indications and procedures for second-look surgery in acute mesenteric ischemia.
AB  - Acute mesenteric ischemia (AMI) is a highly lethal clinical entity associated
      with high morbidity and mortality. Bowel necrosis often results, usually
      necessitating bowel resection; however, deciding on the extent of resection is
      problematic as accurate identification of ischemic bowel that may undergo
      subsequent infarction is difficult. Therefore, a second-look laparotomy after the
      first operation is usually recommended. While the second-look procedure is widely
      accepted, its optimal indications and mode are still controversial, raising
      questions such as "second-look or not?," "planned relaparotomy or relaparotomy on
      demand?," and "open or laparoscopic?" In this review we discuss the relevant
      literature and reassess the role of the second-look operation in the treatment of
      AMI.

PMID- 20676852
TI  - BiClamp forceps significantly shorten the operation time for breast surgery.
AB  - PURPOSE: A novel approach was introduced for breast surgery using the BiClamp, a
      new bipolar thermal energy device, to avoid complications and to shorten the time
      required for the dissection of the axillary lymph nodes. METHODS: Thirty-six
      patients with early breast cancer were assessed. The surgical parameters were
      compared between the procedures performed using the BiClamp technique (n = 14)
      and conventional surgery with suture ligation (n = 22). The parameters included
      the operation time, blood loss, and discharge on the first postoperative day. In
      addition, each of those parameters was compared between the patients with a high
      body mass index (BMI) (>22) and a low BMI (< or =22). The sealed vessels were
      examined histologically and heat-associated morphological vessel wall alterations
      were evaluated. RESULTS: The operation time was significantly shorter in the
      BiClamp group than in the control group (P = 0.017, 90 +/- 18 vs 115 +/- 33 min).
      In addition, the blood loss in the BiClamp group tended to be smaller than in the
      control group, but the difference was not significant (P = 0.54, 61 +/- 47 vs 74
      +/- 67 g). No other parameters showed any significant differences between the two
      groups. CONCLUSION: The BiClamp thermofusion technique was safe and useful in
      breast surgery involving axillary dissection.

PMID- 20676853
TI  - Outpatient management of post-pneumonectomy and post-lobectomy empyema using the
      vacuum-assisted closure system.
AB  - PURPOSE: The conventional management of a post-pneumonectomy (PPE) and post
      lobectomy empyema (PLE) necessitates an open window, wound packing, frequent
      wound debridement, and prolonged hospitalization. We studied the feasibility of
      outpatient therapy in this patient population using the vacuum-assisted closure
      (VAC) therapy system. METHODS: From September 2005 to November 2007, six patients
      with PPE and PLE with or without a bronchopleural fistula underwent outpatient
      therapy using a VAC system. After debridement and closure of the bronchial
      fistula, a VAC system was applied and the patient was discharged. The patient
      returned for debridement under anesthesia and VAC replacement every 7-10 days.
      Once the pleural space was cleaned, the residual space was obliterated, and the
      wound was closed over suction catheters. Of the six patients, two developed
      recurrent infection after the closure that required repeated VAC dressings and
      flap closures. RESULTS: The outpatient use of the VAC system in patients with PPE
      and PLE avoided the need for any daily painful dressing changes and significantly
      decreased the total length of hospitalization and the time to closure of the
      empyema space, and thus increased the overall patient satisfaction. CONCLUSIONS:
      Our results suggest that outpatient VAC therapy of PPE and PLE is feasible and
      beneficial.

PMID- 20676854
TI  - Surgical outcome of an anatomical resection of clinical stage IA non-small cell
      lung cancer assisted with a video-thoracoscopy.
AB  - PURPOSE: Video-assisted resections of non-small cell lung cancer (NSCLC) are now
      performed worldwide; however, its validity as an oncologic surgical modality
      still remains to be elucidated. METHODS: A consecutive series of 139 clinical
      stage IA NSCLC patients who underwent video-thoracoscopy combined with an access
      thoracotomy (VATS) or a standard open surgery (OR) were prospectively
      investigated regarding their status after undergoing a nodal dissection and their
      disease-free survival. RESULTS: Both the VATS (72 patients) and OR groups (67
      patients) contained comparable populations in terms of age, sex, histological
      type, and surgical morbidity, and showed comparable operation time and estimated
      blood loss. The number of dissected nodes on the right/left side was 25.3/19.5 in
      the VATS group and 25.6/22.9 in the OR group (P = 0.923/0.313). A pathologic
      examination revealed the proportion of upstaged patients was 18% in the VATS
      group and 27% in the OR group (P = 0.439). The disease-free survival rates for
      both groups were almost completely identical, with rates at 5 years of 76.5% and
      79.2%, respectively (P = 0.908). CONCLUSION: VATS is therefore considered to be
      an adequate oncologic surgery for clinical stage IA NSCLC, and is also
      appropriate for the postoperative adjuvant era.

PMID- 20676855
TI  - Predictors of postoperative survival in patients with locally advanced non-small
      cell lung carcinoma.
AB  - PURPOSE: A surgical resection for locally advanced non-small cell lung carcinoma
      (NSCLC) remains controversial. This study analyzed the clinicopathological
      profile and surgical outcome of patients with locally advanced NSCLC to identify
      the predictors of survival. METHODS: This study retrospectively analyzed clinical
      data from 86 patients with pathological T3 or T4 primary NSCLC treated at Chiba
      University Hospital, and evaluated prognostic factors. RESULTS: Sixty-eight of 86
      cases were treated with a complete resection, and 18 were evaluated as an
      incomplete resection. The 5-year overall survival rate of all cases was 45.7%.
      Univariate analyses of survival were performed to determine the predictors of
      overall survival in patients with pathological T3 or T4 NSCLC. Age of 70 years or
      more, tumor length more than 5 cm, lymph node metastases, incomplete resection,
      and histology of non-adenocarcinoma were significantly associated with an
      unfavorable prognosis. Multivariate analyses revealed that older age, incomplete
      resection, and lymph node metastases were independent predictors of shorter
      survival. CONCLUSION: A complete resection for selected cases is acceptable in
      the management of T3 or T4 NSCLC.

PMID- 20676856
TI  - Chest injuries associated with earthquakes: an analysis of injuries sustained
      during the 2008 Wen-Chuan earthquake in China.
AB  - PURPOSE: The goal of this study was to analyze the patterns, therapeutic
      modalities, and short-term outcomes of patients with chest injuries in the
      aftermath of the Wen-Chuan earthquake, which occurred on May 12, 2008 and
      registered 8.0 on the Richter scale. METHODS: Of the 1522 patients who were
      referred to the West China Hospital of Sichuan University from May 12 to May 27,
      169 patients (11.1%) had suffered major chest injuries. The type of injury, the
      presence of infection, Abbreviated Injury Score (AIS 2005), New Injury Severity
      Score (NISS), treatment, and short-term outcome were all documented for each
      case. RESULTS: Isolated chest injuries were diagnosed in 129 patients (76.3%),
      while multiple injuries with a major chest trauma were diagnosed in 40 patients
      (23.7%). The mean AIS and the median NISS of the hospitalized patients with chest
      injuries were 2.5 and 13, respectively. The mortality rate was 3.0% (5 patients).
      CONCLUSIONS: Most of the chest injuries were classified as minor to moderate
      trauma; however, coexistent multiple injuries and subsequent infection should be
      carefully considered in medical response strategies. Coordinated efforts among
      emergency medical support groups and prior training in earthquake preparedness
      and rescue in earthquake-prone areas are therefore necessary for efficient
      evacuation and treatment of catastrophic casualties.

PMID- 20676857
TI  - An evaluation of the surgical morbidity of polyglycolic acid felt in pulmonary
      resections.
AB  - PURPOSE: Several methods using various materials have so far been reported to
      repair pulmonary air leaks, which is an essential problem in general thoracic
      surgery. Although the efficacy of these materials has been often discussed, the
      safety has only rarely been examined. This study evaluated the safety of
      polyglycolic acid (PGA) felt, one of the most commonly materials employed at this
      institute. METHODS: A total of 1026 patients who underwent a pulmonary resection
      from January 2000 to December 2007 were enrolled in this study. The status of PGA
      use, type of surgery, and incidence and type of surgical site infection (SSI)
      were reviewed retrospectively from the clinical records. RESULTS: Three hundred
      and forty-four patients were treated with PGA. Although two patients in the PGA
      group underwent a reoperation, PGA itself was not causative. In one case, the PGA
      felt strictly adhered to both the parietal and visceral pleura. CONCLUSION:
      Polyglycolic acid felt can be used safely in general thoracic surgery and did not
      influence the incidence or type of SSI. Surgeons should be aware of the
      possibility of adhesion around the material at the time of re-operation, and the
      criteria of PGA use should be strictly discussed.

PMID- 20676858
TI  - Assessment of pelvic hemodynamics during an open repair of an infrarenal
      abdominal aortic aneurysm.
AB  - PURPOSE: To assess the pelvic circulation during abdominal aortic aneurysm (AAA)
      repair by measuring the inferior mesenteric artery stump pressure (IMA-SP),
      penile blood flow, and gluteal blood flow. METHODS: Twenty males were selected
      for this study. An aorto-bi-common iliac arteries (CIA) graft replacement was
      performed in ten patients (Group Bi-CIA). An aorto-right-CIA/left-external iliac
      artery (EIA) graft replacement was performed in five (Group Lt-EIA). The other
      five underwent an aorto-right-EIA/left-CIA anastomosis (Group Rt-EIA). The right
      graft limb was anastomosed first, followed by the left limb in all of the
      patients. Pelvic circulation was monitored during aortic reconstruction,
      including the IMA-SP index (IMA-SPI), penile brachial pressure index (PBI) by
      pulse-volume plethysmography, and gluteal tissue oxygenation metabolism with near
      infrared spectroscopy by monitoring the gluteal tissue oxygenation index (TOI)
      bilaterally. RESULTS: The PBI and bilateral gluteal TOI became depressed in all
      patients during proximal aortic clamping. However, there was no significant
      change in IMA-SPI in each group. The PBI and bilateral gluteal TOI in all groups
      recovered to the baseline values after completion of bilateral graft limb
      anastomosis. CONCLUSIONS: IMA-SPI is likely to reflect collateral circulation
      mainly from the superior mesenteric artery. The penile blood flow and bilateral
      gluteal blood flow therefore seem to be supplied via the bilateral hypogastric
      arteries or the profunda femoris arteries.

PMID- 20676859
TI  - The serum level of carcinoembryonic antigen in drainage venous blood is not a
      sensitive predictor of metachronous hepatic metastasis for patients with
      colorectal cancer.
AB  - PURPOSE: To establish whether the serum levels of carcinoembryonic antigen (CEA)
      in drainage venous blood (d-CEA) is a better predictor of prognosis or survival
      than the preoperative CEA level in peripheral venous blood (p-CEA), and how these
      two CEA levels compare as predictive factors for metachronous hepatic metastasis.
      METHODS: We examined specimens of peripheral and drainage venous blood from 119
      patients with colorectal cancer. RESULTS: There was a strong positive correlation
      between p-CEA and d-CEA levels. The 5-year survival rates were 81.5% and 80.2%
      for patients with normal p-CEA and d-CEA levels (< or =5 ng/ml), respectively,
      and 68.4% and 71.1% for those with abnormal p-CEA and d-CEA levels (>5 ng/ml).
      The p-CEA and d-CEA levels were both normal in seven of ten patients with
      metachronous hepatic metastasis. The CEA gradient between the d-CEA and p-CEA
      levels (d-p CEA gradient) was not a significant predictive factor for hepatic
      metastases. CONCLUSIONS: There was virtually no change between preoperative p-CEA
      and d-CEA levels. These findings suggest that the d-CEA level is not a predictor
      for metachronous hepatic metastasis and that measuring p-CEA levels is sufficient
      in the surveillance of colorectal cancer.

PMID- 20676860
TI  - Efficacy of lanolin and bovine type I collagen in the treatment of childhood anal
      fissures: a prospective, randomized, controlled clinical trial.
AB  - PURPOSE: We designed an open-labeled, prospective, randomized, controlled
      clinical trial to test the efficacy of topical lanolin ointment (PureLan) and
      bovine type I collagen spray (Gelfix) in the treatment of childhood anal
      fissures. METHODS: Seventy-one children with acute anal fissure were divided
      randomly into three groups: group I (control; n = 25), group II (PureLan; n =
      28), and group III (Gelfix; n = 18). All children were assigned to have warm sitz
      baths, topical analgesic creams, and stool softeners. Patients in groups II and
      III were also treated with topical lanolin ointment and bovine type I collagen,
      respectively. All children were re-examined 4 weeks later. RESULTS: Complete
      healing of the anal fissure was observed in 68% of the group I patients, but in
      92.9% and 100% of the group II and III patients, respectively. The difference
      among groups was significant in terms of complete fissure healing (P = 0.003),
      but the efficacy of topical lanolin ointment and bovine type I collagen spray did
      not differ significantly (P = 0.078). CONCLUSION: Our data suggest that topical
      lanolin ointment and bovine type I collagen spray are effective in the treatment
      of acute anal fissure in children.

PMID- 20676861
TI  - Comparison of the classic Limberg flap and modified Limberg flap in the treatment
      of pilonidal sinus disease: a retrospective analysis of 416 patients.
AB  - PURPOSE: Pilonidal sinus disease (PSD) is usually seen on the sacrococcygeal
      region in adolescent patients. The current study analyzed the outcome of the
      rhomboid excision and the Limberg flap procedure (cLF) in comparison to the
      modified Limberg flap procedure (mlF) for PSD. METHODS: Four hundred and sixteen
      patients with PSD were operated on under spinal or general anesthesia by cLF and
      mlF. The patients were divided into two groups. In Group 1, cLF was performed on
      211 patients. In Group 2, mlF was performed on 205 patients. RESULTS: No
      significant difference was detected between Groups 1 and 2 in terms of sex, age,
      preoperative disease period, follow-up time, the mean hospital stay, and
      hypoesthesia. The mlF group had better clinical results than the cLF group. The
      recurrence rate was statistically higher in the cLF group 1 than in the mlF group
      (P = 0.036). The time to return to work, time to walk without pain, and time to
      be able to sit on the toilet without pain were longer in the cLF group (P =
      0.001). The maceration and wound infection rate were statistically higher in the
      cLF group than in the mlF group (P = 0.020 and P = 0.019, respectively).
      CONCLUSION: The mlF is a more effective treatment than cLF for the surgical
      management of PSD.

PMID- 20676862
TI  - Surgical site infections in a tertiary health care center: prospective cohort
      study.
AB  - PURPOSE: To investigate the incidence and risk factors associated with the
      development of surgical site infections (SSIs) using the National Nosocomial
      Infection Surveillance (NNIS). METHODS: A prospective cohort study was conducted
      at a tertiary health care center. Infection control personnel collected general
      and health care related data about patients. The NNIS risk index was calculated
      on the basis of data relating to the operation: wound contamination class,
      duration of surgery, and the American Society of Anesthesiologists (ASA) score.
      RESULTS: A total of 5109 surgical procedures were included in the study. The
      overall cumulative incidence rate was 6.3%. The incidence of SSIs was 2.3% (63.5%
      of operative procedures), 8.3% (29.7%), 34.6% (6.2%), and 43.3% (0.6%), in
      patients with 0, 1, 2, and 3 risk index, respectively. The length of hospital
      stay (OR: 1.0; 95% CI: 1.053-1.075), preoperative length of stay (odds ratio
      [OR]: 1.9; 95% confidence interval [CI]: 1.953-1.981), antibiotic prophylaxis
      (OR: 2.5; 95% CI: 1.421-4.628), drainage (OR: 1.7; 95% CI: 1.360-2.353), ASA
      score (OR: 1.5; 95% CI: 1.235-1.946), class of wound contamination (OR: 2.0; 95%
      CI: 1.745-2.003), and NNIS risk index (OR: 1.3; 95% CI: 1.063-1.7) were
      independently associated with an increased risk for SSIs. Staphylococcus aureus
      was the most frequently isolated microorganism, 64% of them being methicillin
      resistant. CONCLUSION: The aim of this study was to investigate the most
      important risk factors associated with the development of surgical site
      infections (SSIs). Therefore, greater attention has been given to adherence to
      recommendations for the prevention and control of SSIs as well as to antibiotic
      prophylaxis protocols.

PMID- 20676863
TI  - Small solid pseudopapillary tumor of the pancreas in a 32-year-old man: report of
      a case.
AB  - A solid pseudopapillary tumor (SPT) of the pancreas is a rare neoplasm that
      mainly occurs in young women. We herein report the case of a small SPT arising
      from the head of the pancreas in an asymptomatic 32-year-old man, plus a
      literature review of this tumor. A 32-year-old man was admitted to our department
      at Kumamoto University Hospital for the evaluation of a pancreatic mass. The
      tumor had central necrosis, which was poorly perfused on contrast-enhanced
      computed tomography (CT) and which had a high intensity on T2-weighted magnetic
      resonance imaging (MRI). Histology revealed the lesion to be a solid
      pseudopapillary tumor of the pancreas, with the characteristic pseudopapilla
      formation and central degeneration. However, no capsule formation was observed.
      The tumor was positive for CD56, CD10, alpha1-antitrypsin, alpha1
      antichymotrypsin, beta-catenin, and progesterone receptor. However, the tumor was
      negative for pancreatic hormones, chromogranin-A, carcinoembryonic antigen, and
      carbohydrate antigen 19-9. We diagnosed the patient to have an SPT based on these
      histological findings. Small-sized solid pseudopapillary tumors of the pancreas
      are being increasingly recognized because of the recent advances in CT and MRI.
      We should also consider SPT even if it occurs in a male when the tumor contains
      necrosis-suspected areas which are poorly perfused on contrast-enhanced CT with a
      high intensity on T2-weighted MRI.

PMID- 20676864
TI  - Xanthogranulomatous cholecystitis complicated with primary sclerosing
      cholangitis: report of a case.
AB  - Patients with primary sclerosing cholangitis (PSC) are at an increased risk for
      biliary tract carcinoma. The preoperative diagnosis of a biliary tract tumor as a
      malignancy is difficult, even using new modalities such as multidetector computed
      tomography (MD-CT), magnetic resonance cholangiopancreatography (MRCP),
      endoscopic retrograde cholangiography (ERC), and (18)F-fluorodeoxyglucose
      positron emission tomography (FDG-PET). Surgery is considered to be first line of
      treatment when these examinations suggest the presence of malignancy in the
      biliary tract, depending on both the curability of the cancer and the impaired
      liver function due to PSC. The management of gallbladder masses in patients with
      PSC remains problematic due to difficulties with the precise diagnosis and
      adequate surgery. Xanthogranulomatous cholecystitis (XGC) is a type of chronic
      cholecystitis, and sometimes coexists with gallbladder cancer. It is very
      difficult to make a preoperative diagnosis differentiating these two diseases.
      This report presents the case of a patient with XGC, who had been suspected of
      having gallbladder cancer before surgery, because the tumorous lesion emerged
      within a year and showed a focally increased uptake by FDG-PET during the follow
      up for PSC for years. This is the first case of XGC discovered during treatment
      for PSC.

PMID- 20676865
TI  - Heterotopic gastric mucosa in the gallbladder: report of two cases.
AB  - This report presents two cases of heterotopic gastric mucosa in the gallbladder.
      In case 1, the patient was a 43-year-old man who presented with diarrhea and
      fever. Abdominal ultrasonography showed a sessile polypoid lesion in the body of
      the gallbladder that grew over 2 months. Gallbladder carcinoma was suspected and
      a cholecystectomy was performed. Examination of an intraoperative frozen specimen
      of the elevated lesion in the body of the gallbladder suggested a gallbladder
      carcinoma invading the subserosal layer. A bile duct resection and regional lymph
      node dissection were performed. However, the postoperative permanent sections
      revealed heterotopic gastric mucosa in the gallbladder. Case 2 was an 80-year-old
      man. Screening abdominal ultrasonography revealed a sessile polypoid lesion in
      the gallbladder. This lesion was correctly diagnosed as heterotopic gastric
      mucosa in the gallbladder by the intraoperative frozen examination. The pertinent
      literature on this topic is reviewed.

PMID- 20676866
TI  - Successful embolization therapy for bleeding from jejunal varices after
      choledochojejunostomy: report of a case.
AB  - We report a case of successful embolization of jejunal varices that were the
      cause of massive gastrointestinal bleeding from a choledochojejunostomy site,
      resulting from obstruction of the extrahepatic portal vein. A 42-year-old man who
      had undergone choledochojejunostomy for intrahepatic and choledochal stones was
      readmitted after he started passing massive dark bloody stools. Gastrointestinal
      endoscopic examination and angiography could not identify the source of bleeding.
      Percutaneous transhepatic portography showed obstruction of the right branches of
      the portal vein. The formation of jejunal varices at the site of
      choledochojejunostomy was revealed by portography and by cholangioscopy,
      suggesting the varices as the cause of massive bleeding. Bleeding could not be
      controlled long-term by cholangioscopic sclerosing therapy. We finally stopped
      the bleeding by embolizing a jejunal vein to the afferent loop.

PMID- 20676867
TI  - Epidemiology of adenocarcinoma of the esophagus, gastric cardia, and upper
      gastric third.
AB  - The incidence of adenocarcinoma of the esophagus and esophagogastric junction
      (gastric cardia) has risen rapidly over the past three decades in the United
      States and northern Europe. This increase had been most dramatic among White
      males. The majority of these cancers arise from Barrett's esophagus. However,
      less than 10% of the patients with esophageal adenocarcinoma were known to have
      Barrett's esophagus before. Current evidence indicates that gastroesophageal
      reflux and obesity are major risk factors for adenocarcinoma of the esophagus.
      Abdominal obesity, more prevalent in males, and independent of body mass index,
      seems to be associated with an increased risk of esophageal adenocarcinoma but
      not of cardia adenocarcinoma. This observation may explain the high male:female
      ratio observed in esophageal adenocarcinoma. Tobacco use has also been found as a
      possible risk factor for adenocarcinoma of the esophagus and gastric cardia.
      Infection with Helicobacter pylori and the use of nonsteroidal anti-inflammatory
      drugs might reduce the risk. On the other hand, low intake of fruits, vegetables,
      and cereal fibers seem to increase the risk of esophageal adenocarcinoma.
      Currently, there is no evidence that strongly supports any specific strategy to
      screen a subgroup of the population at risk for adenocarcinoma of the esophagus
      or esophagogastric junction. Future strategies to decrease obesity and tobacco
      use might help to reduce the burden of esophageal adenocarcinoma at least
      partially.

PMID- 20676868
TI  - Clinical classification systems of adenocarcinoma of the esophagogastric
      junction.

PMID- 20676869
TI  - Histopathologic classification of adenocarcinoma of the esophagogastric junction.

PMID- 20676870
TI  - The pathogenesis of Barrett's metaplasia and the progression to esophageal
      adenocarcinoma.
AB  - The most important risk factor for the development of Barrett's esophagus is the
      reflux of both gastric and duodenal contents into the esophagus. The reason why
      Barrett's metaplasia develops only in a minority of patients suffering from
      gastroesophageal reflux disease remains unknown.The exact mechanism behind the
      transition of normal squamous epithelium into specialized columnar epithelium is
      also unclear. It is likely that stem cells are involved in this metaplastic
      change, as they are the only permanent residents of the epithelium. Several
      tumorigenic steps that lead to the underlying genetic instability, which is
      indispensable in the progression from columnar metaplasia to esophageal
      adenocarcinoma have been described. This review outlines the process of
      pathogenesis of Barrett's metaplasia and its progression to esophageal
      adenocarcinoma.

PMID- 20676871
TI  - Differences in the molecular biology of adenocarcinoma of the esophagus, gastric
      cardia, and upper gastric third.
AB  - Adenocarcinoma of the distal esophagus, gastric cardia, and upper gastric third
      are grouped in type I-III by the Siewert classification. This classification is
      based on the endoscopic localisation of the tumor center, and is the most
      important diagnostic tool to group these tumors. On a molecular level, there is
      currently no marker that would allow to differentiate the three different types.
      Furthermore, the Siewert classification was not uniformly used in the recent
      literature, making interpretation and generalization of these results difficult.
      However, several potential targets have been identified that may help to separate
      these tumors by molecular markers, and are summarized in this chapter.

PMID- 20676872
TI  - Clinical staging of adenocarcinoma of the esophagogastric junction.
AB  - Tumors of the esophagogastric junction are among the most frequent and cause
      lethal cancers. Patients often do not present until late in the disease when the
      tumor is sufficiently large to cause obstruction or invasion of the adjacent
      structures, and thus becomes symptomatic. Preoperative staging is critical to
      select those patients whose disease is still locally confined for curative
      surgery. Ideally, clinical staging should accurately predict tumor invasion,
      lymph node involvement, and distant metastases. Upper endoscopy establishes the
      tumor diagnosis by multiple biopsies and defines the tumor type (Siewert I-III),
      based on tumor localization in relation to the endoscopic cardia. Preoperative
      TNM staging has a strong impact on treatment strategy. Endoscopic Ultrasound
      (EUS) determines the T category, and to a lesser extent, the presence of lymph
      node metastases. Multislice Computed Tomography (CT) and 18Fluorode-ocx-glucose
      Positron Emission Computed Tomography (18FDG-PET-CT) provide further information,
      especially about systemic metastases. Diagnostic laparascopy is suggested in
      advanced (CT3/4) Siewert type II-III tumors to exclude peritoneal carcinomatosis.
      This chapter summarizes current staging modalities and their accuracy in clinical
      practice.

PMID- 20676873
TI  - Endoscopic mucosal resection for staging and therapy of adenocarcinoma of the
      esophagus, gastric cardia, and upper gastric third.
AB  - Minamally invasive endoscopic resection techniques allow definitive histological
      staging for dysplasia and early cancer and in many cases curative treatment. In
      Barrett's esophagus with High Grade Dysplasia (HGD) or early mucosal cancer,
      endoscopic mucosal resection (EMR) should be considered both as diagnostic and
      therapeutic first line procedure, with the possibility to repeat the procedure in
      case of residual Barrett's dysplasia or mucosal cancer. In early cancer of the
      the submucosa, surgical resection should be discussed. Endoscopic submucosal
      dissection (ESD) is a useful therapeutic option for HGD or early cancer in the
      squamous epithelium of the esophagus or in the stomach when en bloc resection is
      needed in large lesions.

PMID- 20676874
TI  - Surgical strategies for adenocarcinoma of the esophagogastric junction.
AB  - This chapter summarizes the surgical strategies for adenocarcinomas of the distal
      esophagus, gastric cardia, and subcardial gastric cancer invading the cardia+/
      distal esophagus known as adenocarcinomas of the esophagogastric junction (AEG).
      The different surgical approaches according to the tumor origin, localization,
      and tumor stage are addressed with particular attention to the extent and type of
      resection and appropriate lymphadenectomy (LAD). The classification of AEG
      according to Siewert is helpful for the selection of the surgical strategy. While
      type I tumors benefit from a transthoracic en bloc esophagectomy including a two
      field LAD, type II and III tumors can be treated by an extended total gastrectomy
      with a transhiatal resection of the distal esophagus and LAD of the lower
      mediastinum and the abdominal D2 compartment. Limited resections appear to be 
      possible for early tumor stages in selected cases of type I-III tumors.

PMID- 20676875
TI  - Current status of sentinel lymph node biopsy in adenocarcinoma of the distal
      esophagus, gastric cardia, and proximal stomach.
AB  - The resection of the adenocarcinoma of the esophagogastric junction should be
      considered to the extent of the lymphatic drainage. This, on the other hand,
      depends on the possible lymphatic metastasizing. As an adenocarcinoma of the
      esophagogastric junction is located along the borderline between two visceral
      cavities (mediastinal/abdominal), it can, in principle, metastasize in both
      cavities. There is not, however, an imaging (CT, MRI, PET) that can adequately
      assure the detection of a beginning lymph node metastasis in particular. The
      sentinel lymph node biopsy could provide the beginning of a solution in this
      case. The initial results, with all of the necessary accompanying technical work,
      have been encouraging. The paper presented here provides an introduction to the
      challenge of the SLNB and the background of a specialized surgical therapy of the
      AEG. If a lymph nodal metastasis can be definitely confirmed or ruled out, many
      patients could be spared an unnecessary lymphadenectomy. This is especially
      important at the AEG because minimizing the evasiveness of the surgery with
      adequate radical oncological resection (e.g., without thoracotomy) would mean a
      substantial reduction of postoperative mortality.

PMID- 20676876
TI  - Current diagnosis and future impact of micrometastases for therapeutic strategies
      in adenocarcinoma of the esophagus, gastric cardia, and upper gastric third.
AB  - Esophageal and gastric cancers are aggressive neoplasms with a poor prognosis.
      Although postoperative mortality has declined and rates of complete resection
      have improved considerably, 5 year survival rates are still very low. Early
      metastatic relapse after complete resection of an apparently localized primary
      lesion indicates that disseminated tumor cells, undetectable by current methods,
      may already have been present at the time of surgery, even in patients with
      seemingly early tumor stages. Occult residual tumor disease is suggested when
      either bone marrow or lymph nodes from which tumor relapse may originate are
      affected by micrometastatic lesions undetectable by conventional histopathology.
      The presence of single tumor cells detected by immunohistological methods is
      increasingly regarded as a clinically relevant prognostic factor. The use of
      antibodies against tumor-associated targets enables detection of individual
      epithelial tumor cells in lymph nodes and in bone marrow in various tumor
      entities. The potential role and -benefit of an antibody-based treatment as a
      therapeutic target would be of particular interest in tumors with a notoriously
      poor prognosis such as esophageal cancer and cardia cancer.

PMID- 20676877
TI  - Quality indicators of surgery for adenocarcinoma of the esophagus and
      gastroesophageal junction.
AB  - Surgical treatment of adenocarcinoma of the esophagus and gastroesophageal
      junction is complex and challenging. Huge variation exist in the immediate and
      long term outcomes of such interventions and it is generally accepted that this
      is a direct consequence of the experience of the surgical team. However beside
      surgical quality many other indicators of quality management may influence
      outcome. Definition of the gastroesophageal junction remains controversial and
      the performance of staging procedures i.e. CT scan, endoscopy and fine needle
      aspiration, PET scan still suboptimal. As a result there is disagreement on the
      selection of patients for surgery, type of surgical approach in particular in
      relation to the extent of lymph node dissection as well as the extent of
      esophageal and/or gastric resection. In the design of randomized controlled
      trials comparing primary surgery versus multimodality treatment surgical quality
      criteria are notoriously lacking. It therefore remains a matter of debate which
      patients eventually will benefit from primary surgery versus those who will
      benefit from induction therapy. A lack of surgical quality indicators is also
      very prominent when assessing the value of new surgical technologies such as
      minimally invasive surgery or robotic surgery. Improvements in this wide spectrum
      of aspects is mandatory and will certainly be of great value to further improve
      both short and long term outcome after surgery for these complex cancers.

PMID- 20676878
TI  - Peri-operative and complication management for adenocarcinoma of the oesophagus
      and oesophagigastric junction.
AB  - Surgical resection of oesophageal cancer still offers the only chance of cure for
      this disease. Nevertheless, oesophageal surgery may be accompanied by relevant
      mortality and morbidity, the causes of which can be both directly related to
      surgical technique as well as a large spectrum of non-surgical complications. In
      the last few years, improvements in patient selection and technical advances, as
      well as elaborated peri- and post-operative management, have helped to reduce
      these threats.The following article addresses important aspects of patient
      selection and evaluation, pre-operative preparation, anaesthesia, operative
      prophylaxis of complications, immediate post-operative care and complication
      management. All these factors are important contributions to improve the outcome
      in this challenging medical condition. Nowadays, experienced centres report
      operative mortality rates of around 5% for radical transthoracic resections (Low
      et al. 2007; Or-ringer et al. 2007; Ando et al. 2000; Karl et al. 2000; Whooley
      et al. 2003), down from rates of up to 30 or 40% in previous decades (Earlam and
      Cunha-Melo 1980). Many factors have contributed to these improvements; some
      authors claim large volume centres have a tendency to improve results, mostly due
      to more aggressive management of post-operative complications (Forshaw et al.
      2006; van Lanschot et al. 2001; Smith et al. 2008). The following article
      summarizes the factors that have been identified in the past decades to influence
      the outcome of major surgery for the resection of adenocarcinoma of the
      oesophagus.

PMID- 20676879
TI  - Multimodality therapy for adenocarcinoma of the esophagus, gastric cardia, and
      upper gastric third.
AB  - There is considerable controversy over the level of recommendations from
      randomized trials underpinning management decisions for patients presenting with
      localized adenocarcinoma of the esophagus and esophagogastric junction. Despite a
      paucity of Level 1 recommendations compared with other gastrointestinal sites, in
      particular rectal cancer, there is an emerging consensus in practice to consider
      multimodal approaches in all cases that present with T3 or node-positive disease.
      There is also an optimism that new approaches, including response prediction
      based on sequential 18FDG-PET scanning following induction chemotherapy, and
      novel drugs targeted at EGF, EGFR, VEGF, and tyrosine kinase inhibition may
      improve treatment pathways and outcomes. In this review, we assess the level of
      recommendations from the major published trials and -discuss new trials and
      approaches.

PMID- 20676880
TI  - Metabolic response evaluation by PET during neoadjuvant treatment for
      adenocarcinoma of the esophagus and esophagogastric junction.
AB  - Following several randomized trials, neoadjuvant therapy in adenocarcinoma of
      esophagus and the esophagogastric junction can be seen as an international
      standard. However, in a large proportion of patients the objective response
      achieved is unsatisfactory. These patients do not benefit from neoadjuvant
      therapy, but do suffer from toxic side effects; sometimes progressive and
      appropriate surgical therapy is delayed. For this reason, a diagnostic test that
      can accurately assess tumor response to neoadjuvant therapy might be of crucial
      importance. Response evaluation using CT scan, endoluminal ultrasound, or
      rebiopsy is not reliable. In recent times, response evaluation using 18FGD PET
      after and during neoadjuvant treatment is in the focus of clinical and scientific
      interest. Most studies have evaluated the diagnostic modalities for response to
      neoadjuvant treatment after completion of the treatment. Following the published
      data so far, FDG-PET seems to be less accurate after and during chemoradiation
      than after chemotherapy alone. The data of early response evaluation (14 days
      after the onset of chemotherapy) are very much encouraging; however, they have to
      be evaluated in an international randomized trial. Standardization of PET
      technology as well as defining the thresholds used for the estimation of early
      response is mandatory. So far, FDG-PET does not change treatment in esophageal
      and gastric cancer.

PMID- 20676881
TI  - Molecular response prediction in multimodality treatment for adenocarcinoma of
      the esophagus and esophagogastric junction.
AB  - Cancers arising from the esophagus are becoming more common in the United States
      and Europe. In 2009, an estimate of 14,530 new cases will be diagnosed and more
      than 90% will die of their disease. Esophageal cancer is currently the most
      rapidly increasing cancer in the western world and is coinciding with a shift in
      histological type and primary tumor location. Despite recent improvements in the
      detection, surgical resection, and (radio-) chemotherapy, the overall survival
      (OS) of esophageal cancer remains relatively poor. It is becoming increasingly
      apparent that neoadjuvant chemoradiation followed by surgery may be beneficial in
      terms of increasing resectability and OS compared to surgery alone. Results from
      clinical trials are encouraging; however, they also demonstrated that only
      patients with major histopathological response (pCR) will benefit from
      neoadjuvant therapy. In addition, these therapies are expensive and the prognoses
      of patients who do not respond to trimodality treatment strategies appear to be
      inferior to that of patients who had surgery alone. Accordingly, the development
      of validated predictive molecular markers may not only be helpful in identifying
      EA patients who are more likely to respond, but they will also be critical in
      selecting more efficient treatment strategies with the means of a tailored,
      targeted, and effective therapy to the molecular profile of both the patient and
      their disease while minimizing and avoiding life-threatening toxicities.

PMID- 20676882
TI  - [Implant-free cruciate ligament surgery - 2].

PMID- 20676883
TI  - Changes in religious beliefs and the relation of religiosity to posttraumatic
      stress and life satisfaction after a natural disaster.
AB  - OBJECTIVE: To study changes in religious beliefs and predictors of such changes
      in a community sample exposed to a natural disaster, and to investigate whether
      religiosity was linked to post-disaster mental distress or life satisfaction.
      METHODS: An adult population of 1,180 Norwegian tourists who experienced the 2004
      tsunami was surveyed by a postal questionnaire 2 years after the disaster. Data
      included religiosity, disaster exposure, general psychopathology, posttraumatic
      stress and life satisfaction. RESULTS: Among the respondents, 8% reported
      strengthening and 5% reported weakening of their religious beliefs. Strengthening
      was associated with pre-tsunami mental health problems (OR: 1.82, 95% CI: 1.12
      2.95) and posttraumatic stress (OR: 1.62, 95% CI: 1.22-2.16). Weakening was
      associated with younger age (OR: 0.98, 95% CI: 0.96-1.00) and posttraumatic
      stress (OR: 1.72, 95% CI: 1.23-2.41). Two years after the tsunami, 11% of the
      sample considered themselves to be positively religious. There were no
      significant differences in posttraumatic stress, general psychopathology or life
      satisfaction between religious and non-religious groups. CONCLUSIONS: Religion
      did not play an important role in the lives of Norwegian tsunami survivors in
      general. Respondents who had the greatest disaster exposure were more likely to
      report changes in religious beliefs in both directions. Religious beliefs did not
      prevent post-disaster long-term mental distress, and religiosity was not related
      to higher levels of life satisfaction.

PMID- 20676884
TI  - Upregulation of norepinephrine transporter function by prolonged exposure to
      nicotine in cultured bovine adrenal medullary cells.
AB  - Nicotine acts on nicotinic acetylcholine receptors in the adrenal medulla and
      brain, thereby stimulating the release of monoamines such as norepinephrine (NE).
      In the present study, we examined the effects of prolonged exposure to nicotine
      on NE transporter (NET) activity in cultured bovine adrenal medullary cells.
      Treatment of adrenal medullary cells with nicotine increased [(3)H]NE uptake in
      both a time- (1-5 days) and concentration-dependent (0.1-10 muM) manner. Kinetic
      analysis showed that nicotine induced an increase in the V (max) of [(3)H]NE
      uptake with little change in K (m). This increase in NET activity was blocked by
      cycloheximide, an inhibitor of ribosomal protein synthesis, but not by
      actinomycin D, a DNA-dependent RNA polymerase inhibitor. [(3)H]NE uptake induced
      by nicotine was strongly inhibited by hexamethonium and mecamylamine but not by
      alpha-bungarotoxin, and was abolished by elimination of Ca(2+) from the culture
      medium. KN-93, an inhibitor of Ca(2+)/calmodulin-dependent protein kinase II,
      attenuated not only nicotine-induced [(3)H]NE uptake but also (45)Ca(2+) influx
      in the cells. The present findings suggest that long-term exposure to nicotine
      increases NET activity through a Ca(2+)-dependent post-transcriptional process in
      the adrenal medulla.

PMID- 20676885
TI  - Insights into the phylogeny or arylamine N-acetyltransferases in fungi.
AB  - Previous studies have shown that Eumycetes fungi can acylate arylamine thanks to
      arylamine N-acetyltransferases, xenobiotic-metabolizing enzymes also found in
      animals and bacteria. In this article, we present the results of mining 96
      available fungal genome sequences for arylamine N-acetyltransferase genes and
      propose their phylogeny. The filamentous Pezizomycotina are shown to possess many
      putative N-acetyltransferases, whilst these are often lacking in other fungal
      groups. The evolution of the N-acetyltransferases is best explained by the
      presence of at least one gene in the opisthokont ancestor of the fungi and animal
      kingdoms, followed by recurrent gene losses and gene duplications. A possible
      horizontal gene transfer event may have occurred from bacteria to the
      basidiomycetous yeast Malassezia globosa.

PMID- 20676886
TI  - Inhibition of type 1 diabetes by upregulation of the circadian rhythm-related
      aryl hydrocarbon receptor nuclear translocator-like 2.
AB  - The genetic locus Idd6 is involved in type 1 diabetes development in the non
      obese diabetic (NOD) mouse through its effect on the immune system and in
      particular, on T cell activities. Analysis of congenic strains for Idd6 has
      established the Aryl hydrocarbon receptor nuclear translocator-like 2 (Arntl2) as
      a likely candidate gene. In this study we investigate the role of Arntl2 in the
      autoimmune disease and T cell activation. An Arntl2 expressing plasmid was
      transfected into CD4(+) T cells by nucleofection. Expression levels of cytokines
      and CD4(+) T cell activation markers, cell death, apoptosis, and cell
      proliferation rates were characterized in ex vivo experiments whilst in vivo the
      transfected cells were transferred into NOD.SCID mice to monitor diabetes
      development. The results demonstrate that Arntl2 overexpression leads to
      inhibition of CD4(+) T cell proliferation and decreases in their diabetogenic
      activity without influence on the expression levels of cytokines, CD4(+) T cell
      activation markers, cell death, and apoptosis. Our findings suggest that Arntl2
      at the Idd6 locus may act via the inhibition of CD4(+) T cell proliferation and
      the reduction in the diabetogenic activity of CD4(+) T cells to protect against
      autoimmune type 1 diabetes in the NOD mice.

PMID- 20676887
TI  - Multicenter study on breast reconstruction outcome using Becker implants.
AB  - The use of tissue expanders and implants is the simplest option for breast
      reconstruction following mastectomy. In the 1980s, Hilton Becker introduced a
      round, inflatable breast implant that could be used as a permanent implant. Since
      then, the original implant has been improved in both design and architecture. The
      new Becker device consists of an anatomical implant composed of 35% cohesive
      silicone gel in the outer chamber and 65% normal saline in the inner chamber.
      This multicenter study describes our experience with the new anatomical Becker
      implants in a large series of patients, in both immediate and delayed breast
      reconstruction. We reviewed the clinical records of 204 patients who underwent a
      breast reconstruction with an anatomical Becker-type implant in the sub-muscular
      position between November 2004 and December 2006. Data on the patients'
      characteristics, indications for reconstruction, operative technique, device size
      used, complications, and need for further operations were collected and analyzed.
      A total of 248 breast reconstructions were performed in 204 patients. One hundred
      forty-three patients (70%) underwent an immediate reconstruction; in the
      remaining 61 cases (30%), the breast reconstruction was performed later. The
      patients' age ranged from 26 to 66 years, with a median age of 47.5 years. The
      implant was placed unilaterally in 160 women (78.5%) and bilaterally in the
      remaining 44 (21.5%). Complications occurred in 85 cases (34.2%), in both the
      immediate and delayed reconstruction groups, and were related to wound healing,
      bleeding, seroma, and problems with the inflatable expanders. Iatrogenic implant
      rupture was documented in one case (0.4%). Inflation was impossible in 7 cases
      (2.8%) as a result of valve obstruction (3 cases, 1.2%) and valve displacement (4
      cases, 1.6%). Implant malposition was the most troublesome complication; indeed,
      34 patients (13.7%) complained of device malposition. Capsular contracture was
      assessed in all the patients. Significant capsular contracture (Baker grade III
      and IV) was detected in 6 cases (2.4%) at the follow-up approximately 1 year
      after surgery. Breast reconstruction with permanent inflatable expanders is
      widely acknowledged as a useful technique for breast cancer patients undergoing
      simple or modified radical mastectomy. The use of this device eliminates the need
      to replace a temporary tissue expander with a breast implant, thus avoiding a
      second operation. Although we believe autologous tissues afford the best method
      of reconstruction in the majority of patients, the results of our study show that
      expander implant placement may yield a reasonable reconstruction.

PMID- 20676888
TI  - Evaluating the national land cover database tree canopy and impervious cover
      estimates across the conterminous United States: a comparison with photo
      interpreted estimates.
AB  - The 2001 National Land Cover Database (NLCD) provides 30-m resolution estimates
      of percentage tree canopy and percentage impervious cover for the conterminous
      United States. Previous estimates that compared NLCD tree canopy and impervious
      cover estimates with photo-interpreted cover estimates within selected counties
      and places revealed that NLCD underestimates tree and impervious cover. Based on
      these previous results, a wall-to-wall comprehensive national analysis was
      conducted to determine if and how NLCD derived estimates of tree and impervious
      cover varies from photo-interpreted values across the conterminous United States.
      Results of this analysis reveal that NLCD significantly underestimates tree cover
      in 64 of the 65 zones used to create the NCLD cover maps, with a national average
      underestimation of 9.7% (standard error (SE) = 1.0%) and a maximum
      underestimation of 28.4% in mapping zone 3. Impervious cover was also
      underestimated in 44 zones with an average underestimation of 1.4% (SE = 0.4%)
      and a maximum underestimation of 5.7% in mapping zone 56. Understanding the
      degree of underestimation by mapping zone can lead to better estimates of tree
      and impervious cover and a better understanding of the potential limitations
      associated with NLCD cover estimates.

PMID- 20676889
TI  - A case history of the science and management collaboration in understanding
      hypoxia events in Long Bay, South Carolina, USA.
AB  - Communication of knowledge between the scientific and management communities is a
      difficult process complicated by the distinctive nature of professional career
      goals of scientists and decision-makers. This article provides a case history
      highlighting a collaboration between the science and management communities that
      resulted from a response to a 2004 hypoxia, or low dissolved oxygen, event in
      Long Bay, off Myrtle Beach, South Carolina. A working group of scientists and
      decision-makers was established at the time of the event and has continued to
      interact to develop a firm understanding of the drivers responsible for hypoxia
      formation in Long Bay. Several factors were found to be important to ensure that
      these collaborative efforts were productive: (1) genuine interest in
      collaboratively working across disciplines to examine a problem; (2) commitment
      by agency leadership, decision-makers, and researchers to create successful
      communication mechanisms; (3) respect for each others' perspectives and an
      understanding how science and management are performed and that they are not
      mutually exclusive; (4) networking among researchers and decision-makers to
      ensure appropriate team members are involved in the process; (5) use of decision
      maker input in the formulation of research and monitoring projects; and (6)
      commitment of resources for facilitation to ensure that researchers and decision
      makers are communicating effectively.

PMID- 20676890
TI  - On the determination of evolutionary outcomes directly from the population
      dynamics of the resident.
AB  - In order to determine the possible evolutionary behaviour of an ecological system
      using adaptive dynamics, it is necessary in an ab initio calculation to find the
      fitness and its derivatives at a singular point. It has been suggested that the
      possible evolutionary behaviour can be predicted directly from the resident
      population dynamics, without the need for calculation, by applying three criteria
      one based on the form of the density dependent rates and two on the role played
      by the evolving parameters. The existing arguments for these criteria are rather
      limited: they apply to systems in which individuals enter an initial class and
      can then move through any number of other population classes sequentially.
      (Extensions are included but only apply for systems of two and three classes.)
      Additionally, many of the arguments depend on the use of a phenomenologically
      motivated fitness (shown equivalent to the standard form but in a rather long and
      indirect manner). The present paper removes all these flaws-the criteria are
      established directly from the standard definition of fitness and individuals can
      enter any class and move through the classes non-sequentially without restriction
      on their number. The criteria thus established underlie a geometric description
      of the singular behaviour in adaptive dynamics which allows direct inferences to
      be made from population dynamics to the possible singular behaviour depending on
      which of the criteria apply and on the nature of the trade-off between evolving
      parameters. The method has the great advantage of leaving the trade-off explicit
      but unspecified.

PMID- 20676891
TI  - Three cotton homeobox genes are preferentially expressed during early seedling
      development and in response to phytohormone signaling.
AB  - Homeodomain-leucine zipper (HD-Zip) proteins are transcription factors unique to
      plants. In this study, three cDNAs (designated as GhHB2, GhHB3 and GhHB4)
      encoding HD-Zip proteins were isolated from cotton cDNA library. GhHB2 gene
      encodes a protein of 300 amino acids, GhHB3 gene encodes a peptide with 254 amino
      acids, and GhHB4 gene encodes a protein of 281 amino acids. The deduced proteins,
      which contain the homeodomain and leucine-rich zipper motif, share relatively
      high similarities with the other plant HD-Zip proteins. Quantitative RT-PCR
      analysis indicated that GhHB3 and GhHB4 were preferentially expressed in
      hypocotyls and cotyledons, whereas GhHB2 gene was predominantly expressed in
      young stems, at relatively high levels in hypocotyls. Expressions of all the
      three genes were up-regulated in roots, hypocotyls and cotyledons after GA(3)
      treatments. Additionally, GhHB4 expression was enhanced by 6-BA treatment. A
      GhHB2 promoter fragment was isolated from cotton by Genome-Walking PCR.
      Expression of GUS gene controlled under GhHB2 promoter was examined in the
      transgenic Arabidopsis plants. Strong GUS staining was detected in cotyledon,
      veins of the emerging leaves and shoot apices of 5- to 15-day-old transgenic
      seedlings, but GUS activity became more and more weak as the seedlings further
      developed. In addition, the promoter activity was induced by exogenous GA,
      indicating that GhHB2 promoter is very active during early seedling development,
      and may be GA-inducible. The results suggested that the three HB genes may
      function in early seedling development of cotton and in response to gibberellin
      signaling.

PMID- 20676892
TI  - Intestinal atresia in association with gastroschisis: a 26-year review.
AB  - PURPOSE: We reviewed our experience with gastroschisis (GS) complicated by
      intestinal atresia over the last 26 years. Our aim was to determine the effect of
      different management strategies employed and the morbidity associated with this
      condition in our unit. METHODS: A retrospective casenote review was carried out.
      Data regarding the operative management of the GS and atresia was recorded.
      Primary outcome measures included time to commence and establish full enteral
      feeds, duration of parenteral nutrition, complications and outcome. RESULTS: Of
      179 neonates with GS, 23 also had intestinal atresia. 13 underwent primary
      closure of the defect, 5 had patch closure and 5 had a silo placed. 4 atresias
      were 'missed' at first operation. The 19 recognised atresias were managed either
      by stoma formation, primary anastomosis or deferred management with subsequent
      primary anastomosis. There was wide variation in the outcomes of patients in each
      group. CONCLUSION: Differences in outcome between the management strategies are
      likely to reflect an inherent variability in patient condition, site of atresia,
      and bowel suitability for anastomosis at first surgery, rather than the mode of
      surgical management. Individual management plans should be tailored to the
      clinical condition of each patient.

PMID- 20676893
TI  - Ultrasonography in pregnant women with antiphospholipid syndrome using salicylic
      acid and heparin.
AB  - PURPOSE: The objective of the present study was to evaluate fetal biometry,
      Doppler values, and perinatal outcomes in pregnant women with antiphospholipid
      syndrome treated with acetylsalicylic acid and heparin. STUDY DESIGN: Twenty-five
      pregnant women with antiphospholipid syndrome using 100 mg/day acetylsalicylic
      acid and 5,000 IU heparin every 12 h were evaluated in this prospective
      observational study. Ultrasonography was performed between 24 and 38 weeks of
      gestational age to assess estimated fetal weight, placental thickness, amniotic
      fluid index, fetal biophysical profile and Doppler evaluation of maternal uterine
      arteries, and fetal middle cerebral and umbilical arteries. Data regarding Apgar
      score, gender, delivery mode, and birth weight and length were recorded after
      birth. RESULTS: The observed values for ultrasonographic assessment and perinatal
      outcomes were not very different from the expected values for normal pregnancies.
      The birth weight was 2863.3 +/- 737.7 g (mean +/- SD) and length was 46.8 +/- 4.2
      cm. Only one newborn (4%) had the 1-min Apgar score <7 and all had the 5-min
      Apgar score >7. CONCLUSION: Gestational and perinatal evaluation of pregnant
      women with antiphospholipid syndrome using both acetylsalicylic acid and heparin
      was reassuring.

PMID- 20676894
TI  - Sudden unexpected death due to inflammatory myofibroblastic tumor of the heart: a
      case report and review of the literature.
AB  - Inflammatory myofibroblastic tumor (IMT) or inflammatory pseudotumor is a rare
      primary cardiac tumor that may result in sudden death. We report a sudden
      unexpected death due to occlusion of the coronary arteries by IMT arising from
      the left coronary cusp of the aortic valve. An 8-year-old child suddenly woke up
      from his sleep with complaint of severe chest pain to his parents, and shortly he
      became unresponsive. He expired 40 min later in the hospital despite
      resuscitation efforts. The postmortem examination revealed a 2.5 * 2 * 1-cm mass
      composed of multiple entangled slender cylindrical fronts, filling the coronary
      sinus and obstructing the coronary ostia. The patient had complained of recurrent
      chest pains about 2 weeks prior to his death. Echocardiogram was conducted on the
      patient but did not recognize the mass. Histological examination of the mass
      established the diagnosis of primary cardiac IMT. The detailed pathological
      findings are described. In addition, the literature is reviewed, and
      pathogenesis, clinical presentation, and the importance of forensic autopsy
      examination are discussed.

PMID- 20676895
TI  - Estimation of effective mass of longish rigid instruments in head impacts.
AB  - Impacts to the head are a common form of body violence and thus a relevant legal
      medical issue. Biomechanical assessment of injury potential has been
      traditionally based on qualitative analysis and experience. The aim of this study
      was to collect benchmark data that would facilitate the assessment of the maximum
      force in head impacts with longish rigid instruments. Series of measurements were
      performed with a specially designed modifiable impactor, and the relationship
      between its inertial properties and its effective mass during the impact was
      studied. The effective mass was defined as the amount of point mass that would,
      if exposed to the same velocity change as the striking end of the instrument,
      produce the same area under the force-time curve as the impactor. The results
      show that the effective mass decreases from approximately 100% of the total body
      mass for very short impactors to about 50% for longer (approximately 70 cm)
      impactors. No influence of the hand/grip force on the effective mass of the
      impactor was found if it was used in a hammer-like manner; other striking
      techniques can lead to substantial increase of the effective mass attributable to
      the hand/grip force.

PMID- 20676896
TI  - Performance and physiological responses to repeated-sprint and jump sequences.
AB  - In this study, the performance and selected physiological responses to team-sport
      specific repeated-sprint and jump sequence were investigated. On four occasions,
      13 team-sport players (22 +/- 3 year) performed alternatively six repeated
      maximal straight-line or shuttle-sprints interspersed with a jump ([RS(+j), 6 *
      25 m] or [RSS(+j), 6 * (2 * 12.5 m)]) or not ([RS, 6 * 25 m] or [RSS, 6 * (2 *
      12.5 m)]) within each recovery period. Mean running time, rate of perceived
      exertion (RPE), pulmonary oxygen uptake (V(O)2), blood lactate ([La](b)), and
      vastus lateralis deoxygenation ([HHb]) were obtained for each condition. Mean
      sprint times were greater for RS(+j) versus RS (4.14 +/- 0.17 vs. 4.09 +/- 0.16
      s, with the qualitative analysis revealing a 82% chance of RS(+j) times to be
      greater than RS) and for RSS(+j) versus RSS (5.43 +/- 0.18 vs. 5.29 +/- 0.17 s;
      99% chance of RSS(+j) to be >RSS). The correlation between sprint and jump
      abilities were large-to-very-large, but below 0.71 for RSSs. Jumps increased RPE
      (Cohen's d +/- 90% CL: +0.7 +/- 0.5; 95% chance for RS(+j) > RS and +0.7 +/- 0.5;
      96% for RSS(+j) > RSS), V(O)2(+0.4 +/- 0.5; 80% for RS(+j) > RS and +0.5 +/- 0.5;
      86% for RSS(+j) > RSS), [La](b) (+0.5 +/- 0.5; 59% for RS(+j) > RS and +0.2 +/-
      0.5; unclear for RSS(+j) > RSS), and [HHb] (+0.5 +/- 0.5; 86% for RS(+j) > RS and
      +0.5 +/- 0.5; 85% for RSS(+j) > RSS). To conclude, repeated- sprint and jump
      abilities could be considered as specific qualities. The addition of a jump
      within the recovery periods during repeated-sprint running sequences impairs
      sprinting performance and might be an effective training practice for eliciting
      both greater systemic and vastus lateralis physiological loads.

PMID- 20676897
TI  - Flywheel resistance training calls for greater eccentric muscle activation than
      weight training.
AB  - Changes in muscle activation and performance were studied in healthy men in
      response to 5 weeks of resistance training with or without "eccentric overload".
      Subjects, assigned to either weight stack (grp WS; n = 8) or iso-inertial
      "eccentric overload" flywheel (grp FW; n = 9) knee extensor resistance training,
      completed 12 sessions of four sets of seven concentric-eccentric actions. Pre-
      and post-measurements comprised maximal voluntary contraction (MVC), rate of
      force development (RFD) and training mode-specific force. Root mean square
      electromyographic (EMG(RMS)) activity of mm. vastus lateralis and medialis was
      assessed during MVC and used to normalize EMG(RMS) for training mode-specific
      concentric (EMG(CON)) and eccentric (EMG(ECC)) actions at 90 degrees , 120
      degrees  and 150 degrees  knee joint angles. Grp FW showed greater (p < 0.05)
      overall normalized angle-specific EMG(ECC) of vastii muscles compared with grp
      WS. Grp FW showed near maximal normalized EMG(CON) both pre- and post-training.
      EMG(CON) for Grp WS was near maximal only post-training. While RFD was unchanged
      following training (p > 0.05), MVC and training-specific strength increased (p <
      0.05) in both groups. We believe the higher EMG(ECC) activity noted with FW
      exercise compared to standard weight lifting could be attributed to its unique
      iso-inertial loading features. Hence, the resulting greater mechanical stress may
      explain the robust muscle hypertrophy reported earlier in response to flywheel
      resistance training.

PMID- 20676898
TI  - Preliminary data on the association between waist circumference and insulin
      resistance in children without a previous diagnosis.
AB  - The aim of the present work was to study the association between different
      anthropometric parameters and insulin resistance (IR) in Spanish schoolchildren
      without a previous diagnosis. A total of 443 Spanish schoolchildren (9-11 years
      of age) were studied in this cross-sectional study. The anthropometric
      measurements collected were weight, height, body circumferences and skinfolds.
      Body mass index (BMI), waist/hip ratio, percentage body fat and fat-free body
      mass were determined. Overnight-fasted blood lipids, insulin and glucose levels
      were analysed, and estimation of IR, taking into account the homeostasis model
      assessment (HOMA), was calculated. The children with IR had higher serum
      triglycerides and insulin levels, were heavier and taller, and had a higher BMI,
      a larger waist circumference, a larger hip circumference, a larger waist/hip
      ratio and thicker bicipital and tricipital skinfolds than those who did not have
      IR. Age, sex, BMI and waist circumference explained 32.0% of the variance in the
      HOMA values; only sex, triglycerides and waist circumference independently
      influenced this variable. A 1-cm increase in waist circumference was associated
      with approximately a 3.8% increase in the mean HOMA value. The children with a
      waist circumference of over the p90 for their age and sex were at greater risk of
      showing IR as measured by the HOMA: odds ratio = 6.94 (2.01-23.91; P < 0.001). In
      conclusion, according to these results, waist circumference is the best
      anthropometric parameter associated with IR in children, and those with a waist
      circumference of over the p90 for their age and sex would appear to be at
      particular risk.

PMID- 20676899
TI  - [Functional imaging in pain research].
AB  - Functional brain imaging techniques allow to noninvasively visualize neuronal
      activity and associated metabolic consequences. In combination with elegant
      experimental paradigms in both healthy volunteers and, increasingly, in patients,
      functional brain imaging has led to a vast accumulation of knowledge concerning
      the CNS mechanisms involved in pain perception and pain modulation in humans. The
      so-called "pain matrix" represents a dynamic network of cortical and subcortical
      brain regions regularly activated by acute pain. This includes the somatosensory
      cortices (SI, SII), insular cortex, the cingulate cortex, prefrontal areas,
      amygdala, thalamus, brainstem and cerebellum. The subjective perception of pain
      is substantially influenced by context-dependent intracortical modulations and
      the descending pain modulatory system. This system includes cingulo-frontal brain
      areas together with specific brainstem nuclei that can exert control over
      nociceptive input at the level of the dorsal horn of the spinal cord. Recent
      studies support the view that a dysfunctional interaction between the ascending
      and descending pain system may contribute to the development or maintenance of
      chronic pain states. Here we provide an overview of the principles, applications,
      key findings and recent advances of functional imaging in pain research.

PMID- 20676900
TI  - Endoscopic and histopathological characteristics suggesting the presence of
      gastric mucosal high grade neoplasia foci in cases initially diagnosed as gastric
      mucosal low grade neoplasia by forceps biopsy in Korea.
AB  - BACKGROUND: As biopsy sites may miss coexisting gastric mucosal high grade
      neoplasia (HGN) foci, making a diagnosis of gastric mucosal low grade neoplasia
      (LGN) based only on forceps biopsy specimens can be inaccurate. Therefore, to
      achieve an accurate diagnosis, endoscopic mucosal resection (EMR) of the entire
      lesion is required. However, EMR can cause serious complications such as
      perforation or bleeding. Considering these points, it is necessary to identify
      the characteristics suggesting coexisting HGN foci in cases initially diagnosed
      as LGN by forceps biopsy. METHODS: Three hundred and five lesions from 282
      consecutive patients were initially diagnosed as LGN by forceps biopsy and later
      resected using EMR. The still photographs from endoscopies and pathology slides
      of these lesions were reviewed. RESULTS: After EMR, 272 lesions (89.2%) were
      finally diagnosed as LGN and 33 lesions (10.8%) were diagnosed as having HGN
      foci, including 1 intramucosal carcinoma. Univariate analysis showed that lesions
      >1.0 cm on endoscopy and lesions with tubulovillous or villous histology on
      forceps biopsy specimens were significantly more frequently found in cases with
      HGN than in LGN cases. Multivariate analysis demonstrated that lesion size >1.0
      cm on endoscopy and findings of tubulovillous or villous histology on forceps
      biopsy specimens were independent risk factors for coexisting HGN foci in cases
      initially diagnosed as LGN by forceps biopsy. CONCLUSIONS: If the lesions
      diagnosed as LGN by forceps biopsy are >1.0 cm on endoscopy or show tubulovillous
      or villous histology, EMR might be considered to avoid the risk of missing HGN
      foci.

PMID- 20676901
TI  - Diacyl glycerol arginine-based surfactants: biological and physicochemical
      properties of catanionic formulations.
AB  - In this paper, we report on a catanionic vesicles-based strategy to reduce the
      cytotoxicity of the diacyl glycerol arginine-based synthetic surfactants 1,2
      dimyristoyl-rac-glycero-3-O-(N(alpha)-acetyl-L-arginine) hydrochloride (1414RAc)
      and 1,2-dilauroyl-rac-glycero-3-O-(N(alpha)-acetyl-L-arginine) hydrochloride
      (1212RAc). The behavior of these surfactants was studied either as pure
      components or after their formulation as pseudo-tetra-chain catanionic mixtures
      with phosphatidylglycerol (PG) and as cationic mixtures with 1,2-dipalmitoyl-sn
      glycero-3-phosphatidylcholine (DPPC) used as control. The antimicrobial activity
      of the negatively charged formulations against Acinetobacter baumannii was
      maintained with respect to the surfactant alone, while a significant improvement
      of the antimicrobial activity against Staphylococcus aureus was observed,
      together with a strong decrease of hemolytic activity. The influence of the net
      charge of the catanionic vesicles on membrane selectivity was studied using model
      membranes. The dynamics of surface tension changes induced by the addition of
      1414RAc/PG aqueous dispersions into phospholipid monolayers composed of
      zwitterionic DPPC as model system for mammalian membranes and of negatively
      charged PG mimicking cytoplasmic membrane of gram-positive bacteria was followed
      by tensiometry. Our results constitute a proof of principle that tuning
      formulation can reduce the cytotoxicity of many surfactants, opening their
      possible biological applications.

PMID- 20676902
TI  - O-GlcNAcylation of the Plum pox virus capsid protein catalyzed by SECRET AGENT:
      characterization of O-GlcNAc sites by electron transfer dissociation mass
      spectrometry.
AB  - The capsid protein of Plum pox virus (PPV-CP) is modified with O-linked beta-N
      acetylglucosamine (O-GlcNAc). In Arabidopsis thaliana this modification is made
      by an O-GlcNAc transferase named SECRET AGENT (SEC). Modification of PPV-CP by
      SEC is hypothesized to have a direct role in the infection process, because virus
      titer and rate of spread are reduced in SEC mutants. Previous studies used
      deletion mapping and site-directed mutagenesis to identify four O-GlcNAc sites on
      the capsid protein that are modified by Escherichia coli-expressed SEC. The
      infection process was not affected when two of these sites were mutated
      suggesting that O-GlcNAcylation of these sites does not have a significant role
      in the infection process or that a subset of the modifications is sufficient.
      Since it is possible that the mutational mapping approach missed or incorrectly
      identified O-GlcNAc sites, the modifications produced by E. coli-expressed SEC
      were characterized using mass spectrometry. O-GlcNAcylated peptides were
      enzymatically tagged with galactose, the products were enriched on immobilized
      Ricinus communis agglutinin I and sequenced by electron transfer dissociation
      (ETD) mass spectrometry. Five O-GlcNAc sites on PPV-CP were identified. Two of
      these sites were not identified in by the previous mutational mapping. In
      addition, one site previously predicted by mutation mapping was not detected, but
      modification of this site was not supported when the mutation mapping was
      repeated. This study suggests that mapping modification sites by ETD mass
      spectrometry is more comprehensive and accurate than mutational mapping.

PMID- 20676903
TI  - Plasma free amino acid kinetics in rainbow trout (Oncorhynchus mykiss) using a
      bolus injection of 15N-labeled amino acids.
AB  - To gain insight into the metabolic design of the amino acid carrier systems in
      fish, we injected a bolus of (15)N amino acids into the dorsal aorta in mature
      rainbow trout (Oncorhynchus mykiss). The plasma kinetic parameters including
      concentration, pool size, rate of disappearance (R(d)), half-life and turnover
      rate were determined for 15 amino acids. When corrected for metabolic rate, the
      R(d) values obtained for trout for most amino acids were largely comparable to
      human values, with the exception of glutamine (which was lower) and threonine
      (which was higher). R(d) values ranged from 0.9 MUmol 100 g(-1) h(-1) (lysine) to
      22.1 MUmol 100 g(-1) h(-1) (threonine) with most values falling between 2 and 6
      MUmol 100 g(-1) h(-1). There was a significant correlation between R(d) and the
      molar proportion of amino acids in rainbow trout whole body protein hydrolysate.
      Other kinetic parameters did not correlate significantly with whole body amino
      acid composition. This indicates that an important design feature of the plasma
      free amino acids system involves proportional delivery of amino acids to tissues
      for protein synthesis.

PMID- 20676904
TI  - Activation of the hexosamine biosynthesis pathway and protein O-GlcNAcylation
      modulate hypertrophic and cell signaling pathways in cardiomyocytes from diabetic
      mice.
AB  - Patients with diabetes have a much greater risk of developing heart failure than
      non-diabetic patients, particularly in response to an additional hemodynamic
      stress such as hypertension or infarction. Previous studies have shown that
      increased glucose metabolism via the hexosamine biosynthesis pathway (HBP) and
      associated increase in O-linked-beta-N-acetylglucosamine (O-GlcNAc) levels on
      proteins contributed to the adverse effects of diabetes on the heart. Therefore,
      in this study we tested the hypothesis that diabetes leads to impaired
      cardiomyocyte hypertrophic and cell signaling pathways due to increased HBP flux
      and O-GlcNAc modification on proteins. Cardiomyocytes isolated from type 2
      diabetic db/db mice and non-diabetic controls were treated with 1 MUM ANG
      angiotensin II (ANG) and 10 MUM phenylephrine (PE) for 24 h. Activation of
      hypertrophic and cell signaling pathways was determined by assessing protein
      expression levels of atrial natriuretic peptide (ANP), alpha-sarcomeric actin,
      p53, Bax and Bcl-2 and phosphorylation of p38, ERK and Akt. ANG II and PE
      significantly increased levels of ANP and alpha-actin and phosphorylation of p38
      and ERK in the non-diabetic but not in the diabetic group; phosphorylation of Akt
      was unchanged irrespective of group or treatment. Constitutive Bcl-2 levels were
      lower in diabetic hearts, while there was no difference in p53 and Bax.
      Activation of the HBP and increased protein O-GlcNAcylation in non-diabetic
      cardiomyocytes exhibited a significantly decreased hypertrophic signaling
      response to ANG or PE compared to control cells. Inhibition of the HBP partially
      restored the hypertrophic signaling response of diabetic cardiomyocytes. These
      results suggest that activation of the HBP and protein O-GlcNAcylation modulates
      hypertrophic and cell signaling pathways in type 2 diabetes.

PMID- 20676905
TI  - LC/MS evaluation of metabolism and membrane transport of bombesin peptides.
AB  - Two bombsin peptides, GRPR agonist [Aca-QWAVGHLM-NH(2)] and antagonist [fQWAVGHL
      NHEthyl] were evaluated. We employed the highly sensitive Waters Q-Tof Premier MS
      coupled with a UPLC system to identify the metabolites produced by rat
      hepatocytes or PC-3 human prostate cancer cells; and we utilized the AB/MDS 4000
      Q-Trap LC/MS/MS system with highly sensitive quantitative and qualitative
      performance, to quantitatively analyze the internalization of GRPR agonist and
      antagonist in PC-3 cells. The major metabolites of both GRPR agonist and
      antagonist were the result of peptide bond hydrolysis between W and A which was
      demonstrated by observation of the N-terminal fragment m/z 446 (Aca-QW-OH) for
      agonist and m/z 480 (fQW-OH) for antagonist. Both peptides were also hydrolyzed
      between A and V which formed peaks m/z 517 [Aca-QWA-OH] and m/z 555 (VGHLM-NH2)
      for the agonist and m/z 551 [fQWA-OH] and m/z 452 (VGHL-NHEthyl) for the
      antagonist. The peptide agonist also formed a unique metabolite that resulted
      from hydrolysis of the C-terminal amide. The antagonist showed significantly
      slower metabolism as compared to the agonist in both rat hepatocytes and PC-3
      cells. The antagonist also showed significantly lower PC-3 cell internalization
      rate than that of the agonist. In conclusion, the metabolism profiles of both
      GRPR agonist and antagonist peptides were identified by LC/MS. The antagonist
      peptide was more stable than the agonist peptide in rat hepatocyte incubation.
      One major factor could be the hydrolysis-resistant C-terminal L-NHEthyl group
      compared with the unsubstituted amide of the agonist. Another factor could be
      different amino acid sequences of the agonist and antagonist that may also
      influence the enzymatic hydrolysis. The antagonist ligand is potentially more
      useful for receptor-targeted imaging due primarily to its higher metabolic
      stability.

PMID- 20676907
TI  - Plasma nitroproteome of kidney disease patients.
AB  - 3'-Nitrotyrosine (3NT) is a post-translational modification (PTM) of body fluids
      and tissues that is sustained by chronic inflammation and oxidative stress, two
      main clinical traits of chronic kidney disease (CKD). Despite this background,
      protein targets and their differential susceptibility to in vivo nitration remain
      almost completely unexplored in CKD. This study reports a first investigation of
      plasma nitroproteome in these patients, carried out by both immunorecognition and
      LC-MS/MS techniques. Plasma proteins of chronic and end-stage KD patients showed
      a higher burden of nitration than in healthy controls, but main nitration targets
      appeared to be the same in these populations. Immunoblotting data showed that
      uremic albumin is largely represented in the uremic nitroproteome together with
      fibrinogen chains (A, B and C), transferrin, alpha1-antitrypsin, complement
      factor D, haptoglobin, and IgG light and heavy chains. However,
      immunopurification and affinity chromatography experiments demonstrated that the
      relative content of 3NT on the albumin molecule was very low when compared with
      that of the remaining plasma proteins. The uremic nitroproteome was investigated
      using also plasma proteins obtained by in vivo ultrafiltration from patients
      treated with protein leaking or standard high-flux hemodialyzers. The study of
      these samples revealed the possibility to selectively remove protein nitration
      products during hemodialysis. Identification of intramolecular sites of nitration
      was preliminarily obtained in IgG chains isolated by 2D PAGE and assessed by
      bidimensional tandem mass spectrometry after chemoselective tagging. Further
      studies are needed to confirm at the molecular level the presence of nitrated Tyr
      residues in other proteins tentatively identified as nitration targets in this
      study and to explore the biological meaning of such a selective modification of
      plasma proteins by reactive nitrogen species in uremia and dialysis patients.

PMID- 20676906
TI  - The dynamic stress-induced "O-GlcNAc-ome" highlights functions for O-GlcNAc in
      regulating DNA damage/repair and other cellular pathways.
AB  - The modification of nuclear, mitochondrial, and cytoplasmic proteins by O-linked
      beta-N-acetylglucosamine (O-GlcNAc) is a dynamic and essential post-translational
      modification of metazoans. Numerous forms of cellular injury lead to elevated
      levels of O-GlcNAc in both in vivo and in vitro models, and elevation of O-GlcNAc
      levels before, or immediately after, the induction of cellular injury is
      protective in models of heat stress, oxidative stress, endoplasmic reticulum (ER)
      stress, hypoxia, ischemia reperfusion injury, and trauma hemorrhage. Together,
      these data suggest that O-GlcNAc is a regulator of the cellular stress response.
      However, the molecular mechanism(s) by which O-GlcNAc regulates protein function
      leading to enhanced cell survival have not been identified. In order to determine
      how O-GlcNAc modulates stress tolerance in these models we have used stable
      isotope labeling with amino acids in cell culture to determine the identity of
      proteins that undergo O-GlcNAcylation in response to heat shock. Numerous
      proteins with diverse functions were identified, including NF-90, RuvB-like 1
      (Tip49alpha), RuvB-like 2 (Tip49beta), and several COPII vesicle transport
      proteins. Many of these proteins bind double-stranded DNA-dependent protein
      kinase (PK), or double-stranded DNA breaks, suggesting a role for O-GlcNAc in
      regulating DNA damage signaling or repair. Supporting this hypothesis, we have
      shown that DNA-PK is O-GlcNAc modified in response to numerous forms of cellular
      stress.

PMID- 20676908
TI  - Retropharyngeal and cervicofacial subcutaneous emphysema after maxillofacial
      trauma.
AB  - INTRODUCTION: Subcutaneous emphysema in the cervical region is a well-documented
      event that may occur secondary to tonsillectomy, dental treatment, oropharyngeal
      barotraumas, scaling and root planning therapy, punch biopsy, endotracheal
      intubation, orthognathic surgery, extraction of impacted teeth, or after
      maxillofacial trauma. After trauma episodes, subcutaneous emphysema may be caused
      by a maxillary antral wall fracture that occurs when air pressure is introduced
      into the fascial planes of the connective tissue. Retropharyngeal emphysema is a
      severe condition associated with traumatic aerodigestive tract injury and may be
      associated with life-threatening situations requiring prompt attention and
      diagnosis in order to prevent serious consequences. CASE REPORT: We reported a
      case of cervicofacial and retropharyngeal emphysema in a 54-year-old patient who
      stated concerns after blowing his nose several times after a traumatic episode
      involving orbitozygomatic region. During the patient's hospital course, his
      airway remained stable, and he was discharged from the hospital 7 days later with
      a prognosis of full recovery, excellent occlusion and facial appearance, and
      complete resolution of subcutaneous emphysema.

PMID- 20676909
TI  - Removal of a migrated dental implant from the maxillary sinus after 7 years: a
      case report.
AB  - BACKGROUND: The accidental displacement of dental implants into the maxillary
      sinus is an infrequent but possible complication in dental clinical practice. The
      main cause of implant displacement is the inadequate bone height in the posterior
      maxilla. This event usually occurs during surgery, and it is more rarely reported
      in the post-operative period, especially with long-term follow-ups. CASE REPORT:
      Here, a case of an implant migrated inside the maxillary sinus at the time of
      abutment connection and removed 7 years later is described. DISCUSSION:
      Postoperative recovery was uneventful. To the author's best knowledge, this case
      represents the first report concerning migration of an oral implant into the
      maxillary sinus removed after 7 years.

PMID- 20676910
TI  - Effect and mechanism of 5-aminolevulinic acid-mediated photodynamic therapy in
      esophageal cancer.
AB  - 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) provides a novel
      and promising treatment for esophageal cancer. However, its specific mechanism
      has not been fully elucidated and its efficacy is remarkably varied. This study
      investigated the effect of ALA-PDT on esophageal squamous carcinoma cell line Eca
      109 in vitro and vivo to explore optimal parameters, and evaluated the
      significance of cell apoptosis, cell cycle, ALA-protoporphyrin IX (ALA-PpIX)
      subcellular localization, and expression of Bcl-2 and Bax mRNA in cells to
      understand the mechanism of ALA-PDT for esophageal cancer. How ALA concentration,
      incubation time, and laser irradiation dose influenced the cell proliferation was
      determined by MTT assay. ALA-PpIX subcellular localization was analyzed by
      confocal microscopy. The mRNA changes were detected by quantitative real-time
      polymerase chain reaction (QRT-PCR). Tumor models transplanted with Eca-109 cells
      in nude mice were established (n = 10) and killed (n = 4) at 24 h post-PDT for
      malondialdehyde (MDA) detection and histological study. The remaining mice were
      measured the tumor size for 3 weeks after treatment. Our data show that ALA-PDT
      significantly inhibits cell proliferation (p < 0.05), the PDT efficacy depends on
      the saturation of ALA concentration, incubation time, and laser irradiation dose,
      and the best effect in tumor destruction is at 7-14 days post-PDT. ALA-PpIX is
      localized in mitochondria and cytoplasm. ALA-PDT induces cell apoptosis and
      arrests cell cycle at G0/G1 phase. Bcl-2 is significantly down-regulated while
      Bax is up-regulated (p < 0.05). The results of this study provide references in
      choosing clinical optimal PDT parameters and help in better understanding the PDT
      mechanism for esophageal cancer.

PMID- 20676911
TI  - Involvement of sulfate conjugation and multidrug resistance-associated protein 2
      (Mrp2) in sex-related differences in the pharmacokinetics of garenoxacin in rats.
AB  - In this study, the involvement of sulfate conjugation and drug efflux transporter
      multidrug resistance-associated protein 2 (Mrp2) in sex-related differences in
      the pharmacokinetics of a new quinolone antimicrobial agent, garenoxacin, was
      investigated in Sprague-Dawley (SD) rats and Eisai hyperbilirubinemic rats
      (EHBRs) lacking Mrp2. The disappearance of garenoxacin from plasma in female SD
      rats was significantly faster than that in male SD rats after a single
      intravenous injection of garenoxacin (5 mg/kg). The systemic clearance of
      garenoxacin in female rats was approximately threefold larger than that of male
      rats (2.43 +/- 0.31 and 0.87 +/- 0.06 l/h/kg, respectively), suggesting the
      existence of sex-related differences in the pharmacokinetics of garenoxacin. When
      rats received a constant-rate infusion of garenoxacin, the contribution of
      biliary and renal excretion of garenoxacin was small, and no significant
      difference in the biliary (CL(BILE)) clearance of garenoxacin was observed
      between male and female SD rats. The metabolic clearance [CL(M (SULF))] of
      garenoxacin to garenoxacin sulfate conjugate (which is mainly excreted into the
      bile) in female SD rats was 8.5-fold larger than that in male SD rats (27.9 +/-
      2.94 and 3.28 +/- 0.07 ml/h/kg, respectively). The CL(BILE) of garenoxacin was
      decreased in male and female EHBRs by approximately 50% compared with that in
      male and female SD rats. These results suggest that sulfate conjugation, but not
      Mrp2, is mainly involved in the sex-related differences in the pharmacokinetics
      of garenoxacin.

PMID- 20676912
TI  - Community-acquired macrolide-resistant Mycoplasma pneumoniae pneumonia in
      patients more than 18 years of age.
AB  - A macrolide-resistant Mycoplasma pneumoniae strain was isolated from two patients
      with community-acquired pneumonia. The pneumonia severity score of both patients
      was mild, and rapid clinical improvement was seen after administration of
      fluoroquinolone. Clinical features of macrolide-resistant M. pneumoniae pneumonia
      were identical to those of macrolide-sensitive M. pneumoniae pneumonia. An A-to-G
      transition at position 2063 and 2064, respectively, in domain V of the 23S rRNA
      gene was identified. The minimum inhibitory concentration of erythromycin of
      these isolates was greatly elevated. In Japan, macrolide-resistant M. pneumoniae
      infections are common in pediatric patients but not in adults. However,
      physicians should pay attention to macrolide-resistant M. pneumoniae not only in
      children but also in adults.

PMID- 20676913
TI  - Development of interpretive criteria for tebipenem disk diffusion susceptibility
      testing with Staphylococcus spp. and Haemophilus influenzae.
AB  - Disk diffusion susceptibility interpretive criteria for tebipenem against
      Staphylococcus spp. and Haemophilus influenzae were developed using the Clinical
      and Laboratory Standards Institute (CLSI) guidelines. Tebipenem was tested by
      disk diffusion and broth microdilution methods against 119 clinical isolates of
      Staphylococcus spp. and 102 clinical isolates of H. influenzae. The zone
      diameters of 5-, 10-, and 30-MUg disks were compared with broth microdilution
      minimum inhibitory concentration (MIC) results by scattergram and regression
      analysis. When the MIC breakpoint of 1 MUg/ml was applied to the scattergrams,
      the 10-MUg disk showed good correlation between the zone diameters and the MIC
      values. The corresponding disk diffusion zone diameter breakpoints with the 10
      MUg disk for Staphylococcus spp. were ?22 mm (MIC ?1 MUg/ml) for susceptible, 20
      21 mm (MIC = 2 MUg/ml) for intermediate, and ?19 mm (MIC ?4 MUg/ml) for
      resistant. We also proposed the breakpoint zone diameter of H. influenzae: ?22 mm
      (MIC ?1 MUg/ml) for susceptible. These criteria demonstrated that the categorical
      agreements between disk diffusion and broth microdilution methods for
      Staphylococcus spp. and H. influenzae were 95.0% and 99.0%, respectively. The
      discrepancy rates of these criteria were acceptable to the CLSI guidelines.

PMID- 20676914
TI  - Effective range of reproductive interference exerted by an alien dandelion,
      Taraxacum officinale, on a native congener.
AB  - Reproductive interference (RI), defined as the fitness cost of interspecific
      sexual interactions, such as interspecific pollen transfer (IPT) in plants, is
      ecologically important. Theoretically, RI could result in competitive exclusion,
      as it operates in a frequency-dependent manner. Additionally, IPT may have a
      greater range than resource competition, although information about the range of
      IPT is lacking. In the present study, we measured the range of IPT exerted by
      Taraxacum officinale (an alien species) on a native dandelion, T. japonicum. We
      used two approaches. In one, we analyzed the RI effect on a native seed set at
      three spatial scales. In the second, we tracked IPT from alien to native flower
      heads using fluorescent pigments as markers. We estimated that pollination
      distances were in the order of several meters. These distances exceeded the mean
      distance from each native plant to the nearest alien. As hypothesized, the effect
      of RI reached farther than neighboring individuals. These data indicate the
      spatial range from which alien dandelions should be removed to allow the
      conservation of natives.

PMID- 20676915
TI  - Visual evoked potentials findings in non-affected subjects from a large Brazilian
      pedigree of 11778 Leber's hereditary optic neuropathy.
AB  - To investigate pattern-reversal visual evoked potentials (PRVEP) in asymptomatic
      maternally and non-maternally related members from a large Brazilian 11778/ND4
      LHON pedigree. Transient PRVEP for check sizes 15' and 60' were recorded from
      asymptomatic mutation carriers and non-mutant descendants of affected/non
      affected males, all with best-corrected visual acuity of 20/20. A control group
      of spouses (off-pedigree) was also included. Parameters of N75, P100 and N135
      latencies (ms) and N75-P100 peak-to-peak amplitude (MUV) as well as temporal
      dispersion (latency of N135-latency of N75) were determined. Longitudinal testing
      was obtained in a subseries of carriers in three annual consecutive visits. We
      tested 48 asymptomatic mutation carriers, 19 descendants of affected males, 9
      descendants of non-affected males and 27 off-pedigrees, all of the latter being
      non-mutant. All non-mutant male descendants did not differ from off-pedigree
      controls. Statistically prolonged P100 latencies were found in mutation carriers
      (P = 0.0143) when compared with off-pedigrees for check sizes 15', as well as
      significantly larger temporal dispersions for both check size 15' (P = 0.0012)
      and check size 60' (P = 0.0271). Serial testing in 15 mutation carriers disclosed
      prolonged P100 latencies and larger temporal dispersion that did not change over
      time. Subclinical PRVEP abnormalities were detected in this large group of
      asymptomatic carriers of the 11778/ND4 LHON mutation from the same family,
      confirming and extending previous psychophysical and structural findings of a
      selective involvement of the parvocellular pathway. PRVEP is a useful test to
      characterize and monitor visual dysfunction in this devastating disease.

PMID- 20676916
TI  - Nanoscale fabrication of a peptide layer in cell chip to detect effects of
      environmental toxins on HEK293 cells.
AB  - A cysteine-terminated C(RGD)(4) peptide film was fabricated on a gold electrode
      for improving the attachment of cells. The electrochemical signals of cyclic
      voltammogram from cells on a C(RGD)(4) deposited electrode was enhanced from 0.27
      to 0.49 MUA compared to a bare electrode. The developed cell-based sensor
      determined the effect of bisphenol-A (BPA) and dichlorodiphenyltrichloroethane
      (DTT) on the viability of HEK-293 cells by detecting decrease of reduction peaks
      (1.12-0.15 MUA for BPA and 0.81-0.29 MUA for DDT) after the treatment of
      environmental chemicals. This developed system can be a powerful tool for the
      monitoring of environmental toxicants.

PMID- 20676917
TI  - Enzymatic synthesis of gamma-glutamylglutamine, a stable glutamine analogue, by
      gamma-glutamyltranspeptidase from Escherichia coli K-12.
AB  - The optimal reaction conditions for the synthesis of gamma-glutamylglutamine
      using gamma-glutamyltranspeptidase from Escherichia coli were determined. The
      maximum yield of gamma-glutamylglutamine (110 mM) was obtained using 250 mM L: 
      glutamine and 1.1 U gamma-glutamyltranspeptidase/ml at pH 10.5 and at 37 degrees
      C for 7 h; the conversion of glutamine to gamma-glutamylglutamine was 88%.

PMID- 20676918
TI  - Mutations from a family-shuffling-library reveal amino acid residues responsible
      for the thermostability of endoglucanase CelA from Clostridium thermocellum.
AB  - We constructed a library of chimeras from the major endoglucanase, CelA, of
      Clostridium thermocellum and a less stable endoglucanase CelB from Clostridium
      josui with multiple point mutations using low-fidelity family-shuffling method.
      Mutations that inactivated the enzyme were rapidly eliminated with high
      throughput screening. The activities and thermostabilities of selected variants
      were evaluated, and four amino acid substitutions, K249R, P258S, S329N and E355G,
      were identified as having significant impact on the thermostability of CelA
      without affecting enzymatic activity. In the crystal structure of CelA, most of
      them are away from the activity cleft and are responsible for the stabilization
      of secondary structures.

PMID- 20676919
TI  - Functional conservation of the plant EMBRYONIC FLOWER2 gene between bamboo and
      Arabidopsis.
AB  - A novel EMBRYONGIC FLOWER2 gene, DlEMF2, was isolated from bamboo, Dendrocalamus
      latiflorus. It is 2518 bp in length encoding a protein of 629 amino acids. It was
      expressed in all organs and at a higher level in shoot tissue than in
      inflorescences. Transgenic Arabidopsis plants expressing antisense DlEMF2
      displayed a spectrum of early-flowering phenotypes. Quantitative real-time PCR
      experiments indicated that the antisense transgene DlEMF2 reduced endogenous
      AtEMF2 transcript levels leading to the flowering time reduction. Besides,
      transforming the bamboo DlEMF2 gene into Arabidopsis emf2-1 mutant could rescue
      phenotype in vegetative and reproductive developmental stages, which reveals that
      EMF2 has functional conservation between monocots and eudicots.

PMID- 20676920
TI  - Extracellular expression of keratinase Ker P from Pseudomonas aeruginosa in E.
      coli.
AB  - Keratinase from Pseudomonas aeruginosa KS-1 was expressed constitutively as an
      extracellular protein in Escherichia coli with high specific activity of 3.7
      kU/mg. It was purified fourfold as a 33 kDa monomeric protein by Q-Sepharose ion
      exchange chromatography with a recovery of 95%. It is a serine protease with
      optimal activity at pH 9 and 50 degrees C. It was stable from pH 4 to 12 for 1 h
      with a t(1/2) of 12 min at 70 degrees C. It hydrolyzed haemoglobin > fibrin >
      feather keratin > azo-casein > casein > meat protein > gelatin. Among synthetic
      substrates, it efficiently hydrolyzed N-Suc-ala-ala-pro-phe-pNA, N-Suc-ala-ala
      ala-pNA, N-Suc-ala-ala-pro-leu-pNA and also plasmin substrate, D: -Val-Leu-Lys
      pNA.

PMID- 20676921
TI  - Cloning, characterization and expression of two new polyphenol oxidase cDNAs from
      Agaricus bisporus.
AB  - Two new polyphenol oxidase (PPO) cDNAs (PPO3 and PPO4 cDNAs, accession numbers
      GQ354801 and GQ354802, respectively) were obtained by RACE-PCR from Agaricus
      bisporus. PPO3 cDNA was 1844 bp in length with an open reading frame of 1731 bp,
      while PPO4 cDNA was 2042 bp with an open reading frame of 1836 bp. PPO3 and PPO4
      cDNAs, with 52% identity at the nucleic acid level, encoded a 576-amino acid
      protein of 66.3 kDa and 611-amino acid protein of 68.3 kDa, respectively. Mature
      forms of PPO3 and PPO4 were characterized after removing the specific C-terminal
      region and expressed in Escherichia coli BL21 (DE3) RIPL using pGEX-4T-1 vector.
      The expressed proteins were probed by the anti-A. bisporus PPO antibody but
      without PPO activity. This indicated that the recombinant mature PPO3 and mature
      PPO4 could not form an active center in prokaryotic expression system.

PMID- 20676922
TI  - Translocal ecologies: the Norfolk broads, the "natural," and the international
      phytogeographical excursion, 1911.
AB  - What we consider "nature" is always historical and relational, shaped in
      contingent configurations of representational and social practices. In the early
      twentieth century, the English ecologist A.G. Tansley lamented the pervasive
      problem of international misunderstandings concerning the nature of "nature." In
      order to create some consensus on the concepts and language of ecological plant
      geography, Tansley founded the International Phytogeographical Excursion, which
      brought together leading plant geographers and botanists from North America and
      Europe. The first IPE in August 1911 started with the Norfolk Broads. It was led
      by Marietta Pallis, Tansley's former student at Cambridge. This trip and the work
      of Pallis, neglected in other accounts of this early period of the history of
      ecology, influenced the relations between Tansley and important American
      ecologists H.C. Cowles and F.E. Clements. Understanding "place" as a network of
      relations, our regional focus shows how taking international dialogue, travel and
      interchange into account enriches understanding of ecological practice.

PMID- 20676923
TI  - Parallel particle filters for online identification of mechanistic mathematical
      models of physiology from monitoring data: performance and real-time scalability
      in simulation scenarios.
AB  - OBJECTIVE: Combining mechanistic mathematical models of physiology with
      quantitative observations using probabilistic inference may offer advantages over
      established approaches to computerized decision support in acute care medicine.
      Particle filters (PF) can perform such inference successively as data becomes
      available. The potential of PF for real-time state estimation (SE) for a model of
      cardiovascular physiology is explored using parallel computers and the ability to
      achieve joint state and parameter estimation (JSPE) given minimal prior knowledge
      tested. METHODS: A parallelized sequential importance sampling/resampling
      algorithm was implemented and its scalability for the pure SE problem for a non
      linear five-dimensional ODE model of the cardiovascular system evaluated on a
      Cray XT3 using up to 1,024 cores. JSPE was implemented using a state augmentation
      approach with artificial stochastic evolution of the parameters. Its performance
      when simultaneously estimating the 5 states and 18 unknown parameters when given
      observations only of arterial pressure, central venous pressure, heart rate, and,
      optionally, cardiac output, was evaluated in a simulated bleeding/resuscitation
      scenario. RESULTS: SE was successful and scaled up to 1,024 cores with
      appropriate algorithm parametrization, with real-time equivalent performance for
      up to 10 million particles. JSPE in the described underdetermined scenario
      achieved excellent reproduction of observables and qualitative tracking of
      enddiastolic ventricular volumes and sympathetic nervous activity. However, only
      a subset of the posterior distributions of parameters concentrated around the
      true values for parts of the estimated trajectories. CONCLUSIONS: Parallelized
      PF's performance makes their application to complex mathematical models of
      physiology for the purpose of clinical data interpretation, prediction, and
      therapy optimization appear promising. JSPE in the described extremely
      underdetermined scenario nevertheless extracted information of potential clinical
      relevance from the data in this simulation setting. However, fully satisfactory
      resolution of this problem when minimal prior knowledge about parameter values is
      available will require further methodological improvements, which are discussed.

PMID- 20676924
TI  - Identification and characterization of a putative dihydroorotase, KPN01074, from
      Klebsiella pneumoniae.
AB  - Dihydroorotase (DHO; EC 3.5.2.3) is an essential metalloenzyme in the
      biosynthesis of pyrimidine nucleotides. Here, we identified and characterized DHO
      from the pathogenic bacterium Klebsiella pneumoniae (Kp). The activity of KpDHO
      toward L: -dihydroorotate was observed with K (m) = 0.04 mM and V (max) = 8.87
      mumol/(mg min). Supplementing the standard growth medium with Co2+, Mn2+, Mg2+,
      or Ni2+ increased enzyme activity. The catalytic activity of KpDHO was inhibited
      with Co2+, Zn2+, Mn2+, Cd2+, Ni2+, and phosphate ions. Substituting the putative
      metal binding residues His17, His19, Lys103, His140, His178, and Asp251 with Ala
      completely abolished KpDHO activity. However, the activity of the mutant D251E
      was fourfold higher than that of the wild-type protein. On the basis of these
      biochemical and mutational analyses, KpDHO (KPN01074) was identified as type II
      DHO.

PMID- 20676925
TI  - A new structure-based classification of gram-positive bacteriocins.
AB  - Bacteriocins are ribosomally-synthesized peptides or proteins produced by a wide
      range of bacteria. The antimicrobial activity of this group of natural substances
      against foodborne pathogenic and spoilage bacteria has raised considerable
      interest for their application in food preservation. Classifying these
      bacteriocins in well defined classes according to their biochemical properties is
      a major step towards characterizing these anti-infective peptides and
      understanding their mode of action. Actually, the chosen criteria for
      bacteriocins' classification lack consistency and coherence. So, various
      classification schemes of bacteriocins resulted various levels of contradiction
      and sorting inefficiencies leading to bacteriocins belonging to more than one
      class at the same time and to a general lack of classification of many
      bacteriocins. Establishing a coherent and adequate classification scheme for
      these bacteriocins is sought after by several researchers in the field. It is not
      straightforward to formulate an efficient classification scheme that encompasses
      all of the existing bacteriocins. In the light of the structural data, here we
      revisit the previously proposed contradictory classification and we define new
      structure-based sequence fingerprints that support a subdivision of the
      bacteriocins into 12 groups. The paper lays down a resourceful and consistent
      classification approach that resulted in classifying more than 70% of
      bacteriocins known to date and with potential to identify distinct classes for
      the remaining unclassified bacteriocins. Identified groups are characterized by
      the presence of highly conserved short amino acid motifs. Furthermore,
      unclassified bacteriocins are expected to form an identified group when there
      will be sufficient sequences.

PMID- 20676926
TI  - Aldosterone inhibition and cardiovascular protection: more important than it once
      appeared.
AB  - Aldosterone is present and active all along the cardiovascular continuum.
      Excessive tissue production occurs in cardiovascular diseases including
      myocardial infarction (MI) and heart failure, resulting in a multitude of adverse
      effects in the cardiovascular system necessitating pharmacologic blockade of this
      neurohormone. Both human and animal studies have consistently proven the
      beneficial effects of antialdosteronics in the improvement of: 1) endothelial
      function, 2) modulation of inflammatory mechanisms between blood and the vascular
      wall and 3) reduction of tissue proliferation and cardiovascular remodeling
      leading to different severities of cardiovascular damage. These basic mechanisms
      of anti-aldosterone therapy strongly support the promising data observed in major
      clinical trials with aldosterone blockers in cardiovascular diseases, specially
      in heart failure patients. Whereas aldosterone receptor blockers were initially
      viewed as potassium-sparing diuretics there has been a clear change of concept in
      the past 10 years, mainly following the positive results of RALES with
      spironolactone in chronic heart failure, followed by EPHESUS using eplerenone in
      patients with systolic dysfunction post MI. The significant positive results in
      both studies were a clear support for the inclusion of this pharmacologic
      intervention as first line treatment in most international guidelines for the
      management of heart failure. More recent and ongoing studies are exploring the
      usefulness of this type of intervention in preventing vascular and myocardial
      hypertrophy and remodeling in refractory hypertensive and some hyperfibrotic
      syndromes. There are also provocative studies investigating in the possibility of
      inhibiting atherosclerosis. More recently, some studies are suggesting the
      benefit of aldosterone blockade in sleep apnea. In addition, two large
      multicentric trials, TOPCAT and EMPHASIS are analyzing the potential use of
      antialdosteronics in patients with cardiac insufficiency and preserved systolic
      function and the possibility of extending their indication in systolic heart
      failure to Phase II respectively. New compounds, blocking the synthesis of
      aldosterone instead of blocking its receptor are being developed, and initial
      Phase 2 studies are positive. All of the above results are very interesting, show
      an optimistic future and are consolidating and enlarging the spectrum of
      aldosterone blockade in cardiovascular disorders every day.

PMID- 20676927
TI  - Resveratrol shows vasoprotective effect reducing oxidative stress without
      affecting metabolic disturbances in insulin-dependent diabetes of rabbits.
AB  - PURPOSE: Resveratrol has been shown to have vasoprotective effects by
      upregulating oxidative defense mechanisms in a variety of pathophysiological
      conditions. However, the effect of resveratrol on diabetic oxidative stress and
      vascular and metabolic abnormalities is not completely understood. Therefore,
      this study was designed to evaluate whether long-term resveratrol supplementation
      has a protective effect on vascular function and integrity in association with
      metabolic parameters and oxidative stress in insulin-dependent diabetes. METHODS:
      Diabetes was induced in rabbits with alloxan and maintained for 8 weeks. We used
      a resveratrol dose of 5 mg/L (10 weeks, starting 14 days before alloxan
      injection) and 50 mg/L (8 or 10 weeks, starting concomitantly or 14 days before
      alloxan injection) in the drinking water of rabbits. RESULTS: Relaxation to
      acetylcholine was impaired (control 75.6 +/- 3.59%, versus diabetic 42.23 +/-
      2.53%) and contractions to phenylephrine increased (control 136.89 +/- 2.27%,
      versus diabetic 159.37 +/- 6.27%) in aortas from diabetic animals. These changes
      were associated with increased basal or NAD(P)H-induced superoxide production, as
      well as lipid peroxide and superoxide dismutase (SOD) levels in the aortic
      samples. The maximal relaxation to acetylcholine improved by 75.74 +/- 9.04% in
      diabetic rabbits treated with resveratrol. The increased contractions to
      phenylephrine were not restored to control values after resveratrol treatments,
      but sensitivity to the contractions tended to decrease. Resveratrol increased
      nitrite/nitrate levels and suppressed basal or NAD(P)H-induced superoxide
      production and lipid peroxide levels in the aortas. Importantly, resveratrol
      increased serum insulin levels without affecting blood glucose and the lipid
      profile in diabetic rabbits. Using electron microscopic examinations, resveratrol
      was found to markedly protect the endothelial integrity from diabetes.
      CONCLUSION: Overall, there was no noticeable difference between resveratrol
      treatment groups on the recovery from diabetes. Our results indicate that
      resveratrol alleviates type 1 diabetes-induced vasculopathy by decreasing
      vascular oxidative stress and thereby increasing the bioavailability of nitric
      oxide without changing metabolic abnormalities.

PMID- 20676928
TI  - Peer navigation improves diagnostic follow-up after breast cancer screening among
      Korean American women: results of a randomized trial.
AB  - OBJECTIVE: To test an intervention to increase adherence to diagnostic follow-up
      tests among Asian American women. METHODS: Korean American women who were
      referred for a diagnostic follow-up test (mainly diagnostic mammograms) and who
      had missed their follow-up appointment were eligible to participate in the study.
      Women from two clinics (n = 176) were randomly allocated to a usual care control
      arm or a peer navigator intervention arm. A 20-min telephone survey was
      administered to women in both study arms six months after they were identified to
      assess demographic and socio-economic characteristics and the primary outcome,
      self-reported completion of the recommended follow-up exam. RESULTS: Among women
      who completed the survey at six-month follow-up, self-reported completion of
      follow-up procedures was 97% in the intervention arm and 67% in the control arm
      (p < 0.001). Based on an intent-to-treat analysis of all women who were
      randomized and an assumption of no completion of follow-up exam for women with
      missing outcome data, self-reported completion of follow-up was 61% in the
      intervention arm and 46% in the usual care control arm (p < 0.069). CONCLUSIONS:
      Our results suggest that a peer navigator intervention to assist Korean American
      women to obtain follow-up diagnostic tests after an abnormal breast cancer
      screening test is efficacious.

PMID- 20676929
TI  - A new method for the characterisation and quantitative speciation of base metal
      smelter stack particulates.
AB  - Base metal smelters may be a source of particulates containing metals of
      environmental concern released to the atmosphere. Knowledge of the quantitative
      chemical speciation of particulate releases from base metal smelters will be of
      value in smelter emission fingerprinting, site-specific risk assessments,
      predictions of the behaviour of smelter stack particulates released to the
      environment and in resolving liability issues related to current and historic
      releases. Accordingly, we have developed an innovative approach comprising bulk
      chemical analysis, a leaching procedure, X-ray diffraction analysis and scanning
      electron microscopy/electron probe microanalysis characterisation in a step-wise
      apportioning procedure to derive the quantitative speciation of particulate
      samples from the stacks of three copper smelters designated as A, B and C. For
      the A smelter stack particulates, the major calculated percentages were 29
      CuSO(4), 20 ZnSO(4).H(2)O, 13 (Cu(0.94)Zn(0.06))(2)(AsO(4))(OH), 11 PbSO(4) and
      four As(2)O(3). For the B smelter stack particulates, the primary calculated
      percentages were 20 ZnSO(4).H(2)O, 20 PbSO(4), 12 CuSO(4) and nine As(2)O(3).
      Finally, we calculated that the C smelter stack particulates mostly comprised 34
      ZnSO(4).H(2)O, 19 (Cu(0.84)Zn(0.16))(AsO(3)OH), 11 PbSO(4), 10 As(2)O(3) and nine
      Zn(3)(AsO(4))(2). Between 56% and 67% by weight of the smelter stack
      particulates, including the As, was soluble in water. For these and other
      operations, the data and approach may be useful in estimating metals partitioning
      among water, soil and sediment, as well as predictions of the effects of the
      stack particulates released to the environment.

PMID- 20676930
TI  - Leaching behavior of nitrogen in a long-term experiment on rice under different N
      management systems.
AB  - The leaching behavior of nitrogen was studied in single rice paddy production
      ecosystems in Tsukuba, Japan after 75 years of consistent fertilization regimes
      (no fertilizer, ammonium sulfate, a combination of composted rice straw with
      soybean cake, and fresh clover). During the 75-year period, management was
      unchanged with respect to rice planting density, irrigation, and net N
      fertilization for each field to which an N-source was added. Percolation water
      was collected, from May 2001 to April 2002, using porous suction cups installed
      in the fields at depths of 15, 40, and 60 cm. All water samples were taken to the
      laboratory for the measurement of both NH(4) ( + )-N and NO(3) ( - )-N
      concentrations using a continuous-flow nitrogen analyzer. The result indicated
      that there were significant differences in N leaching losses between treatments
      during the rice growing season. Total N leaching was significantly lower with the
      application of composted rice straw plus soybean cake (0.58 kg N ha( - 1)) than
      with ammonium sulfate (2.41 kg N ha( - 1)), which resulted in N leaching at a
      similar level to that with the fresh clover treatment (no significant
      difference). The majority of this N leaching was not due to NO(3) ( - )-N loss,
      but to that of NH(4) ( + )-N. The mean N leaching for all fertilizer treatments
      during the entire rice growing season was 1.58 kg N ha( - 1). Composted rice
      straw plus soybean cake produced leaching losses which were 65-75% lower than
      those with the application of fresh clover and ammonium sulfate. N accumulation
      resulting from nitrification in the fallow season could be a key source of
      nitrate-N leaching when fields become re-flooded before rice transplanting in the
      following year; particular attention should be paid to this phenomenon.

PMID- 20676931
TI  - Effects of anthropogenic activities on chemical contamination within the Grand
      Canal, China.
AB  - Contamination of nutrients and heavy metals within aquatic system is of great
      concern due to its potential impact on human and animal health. The Grand Canal
      of China, the largest artificial river in the world, is of great importance in
      supplying water resource, transporting cargo, and recreating resident, as well as
      great historical heritage. This study assessed and examined the impact of human
      activities on characters of contamination distribution within the section of the
      Canal in Taihu watershed. Physicochemical parameters of surface water quality
      were determined monthly from the year 2004 to 2006 at 11 sites that were
      influenced by different anthropogenic activities along the Canal. Moreover,
      contaminations at surface sediments (20 cm) at the same locations were also
      analyzed in September 2006. Results showed that the Canal had been seriously
      polluted, which was characterized with high spatial variations in contaminations
      distribution. The sites influenced mainly by industry and urbanization showed
      higher contents of nutrients and lower levels of dissolve oxygen than other
      sites. Concentrations of nitrogen at all studied sites exceeded the worst level
      of surface water quality according to the National Criterion of Surface Water
      Quality, China, with the average values varying from 2.27 to 10.34 mg/L.
      Furthermore, the site influenced mainly by industry (i.e., Site 4) presented the
      highest contents of cadmium (3.453 mg/kg), chromium (196.87 mg/kg), nickel (87.12
      mg/kg), zinc (381.8 mg/kg), and copper (357.32 mg/kg). While sites in vicinity to
      cities had presented relatively higher contents of metals, especially for the
      site located downstream of Changzhou City (Site 3) had presented the highest
      contents of mercury (1.64 mg/kg) and lead (197.62 mg/kg). Copper at Sites 2 to 6,
      Nickel at Sites 2 to 9 except for Site 7, chromium, lead, and zinc at Sites 3 to
      6 had exceeded New York State Department of Environmental Conservation (NYSDEC)
      Severe Effect Level (SEL). By multivariate statistical, nutrient variables,
      companied with V-phen, had contributed the most variation of water quality, while
      nutrient and metals had explained the most part of total variance of
      contaminations in sediment. This study indicated that the canal had been polluted
      severely and urgently need to control.

PMID- 20676932
TI  - High-fluoride groundwater.
AB  - Fluoride (F(-)) is essential for normal bone growth, but its higher concentration
      in the drinking water poses great health problems and fluorosis is common in many
      parts of India. The present paper deals with the aim of establishment of facts of
      the chemical characteristics responsible for the higher concentration of F(-) in
      the groundwater, after understanding the chemical behavior of F(-) in relation to
      pH, total alkalinity (TA), total hardness (TH), carbonate hardness (CH), non
      carbonate hardness (NCH), and excess alkalinity (EA) in the groundwater observed
      from the known areas of endemic fluorosis zones of Andhra Pradesh that have
      abundant sources of F(-)-bearing minerals of the Precambrians. The chemical data
      of the groundwater shows that the pH increases with increase F(-); the
      concentration of TH is more than the concentration of TA at low F(-) groundwater,
      the resulting water is represented by NCH; the TH has less concentration compared
      to TA at high F(-) groundwater, causing the water that is characterized by EA;
      and the water of both low and high concentrations of F(-) has CH. As a result,
      the F(-) has a positive relation with pH and TA, and a negative relation with TH.
      The operating mechanism derived from these observations is that the F(-) is
      released from the source into the groundwater by geochemical reactions and that
      the groundwater in its flowpath is subjected to evapotranspiration due to the
      influence of dry climate, which accelerates a precipitation of CaCO(3) and a
      reduction of TH, and thereby a dissolution of F(-). Furthermore, the EA in the
      water activates the alkalinity in the areas of alkaline soils, leading to
      enrichment of F(-). Therefore, the alkaline condition, with high pH and EA, and
      low TH, is a more conducive environment for the higher concentration of F(-) in
      the groundwater.

PMID- 20676933
TI  - Environmental vanadium distribution, mobility and bioaccumulation in different
      land-use districts in Panzhihua Region, SW China.
AB  - In order to characterize environmental vanadium distribution, mobility, and
      bioaccumulation, a total of 55 soil samples and 36 plant samples were collected
      in four typical land-use districts in Panzhihua region, Southwestern China. Soil
      samples were analyzed with the modified Community Bureau of Reference (BCR)
      sequential extraction procedure, and the content of vanadium in soil and plant
      was determined by ICP-AES. The total content of vanadium was 208.1-938.4 mg kg(
      1) in smelting area, 111.6-591.2 mg kg(-1) in mining area, 94.0-183.6 mg kg(-1)
      in urban park, and 71.7-227.2 mg kg(-1) in agricultural area, respectively, while
      the bio-available content of vanadium was characterized that the polluted areas
      (mining area 18.8-83.6 mg kg(-1), smelting area 41.7-132.1 mg kg(-1)) and the
      unpolluted area (agricultural area 9.8-26.4 mg kg(-1), urban park 9.9-25.2 mg kg(
      1)). In addition, the contamination degree of vanadium in soil was smelting area
      > mining area > agricultural area ~ urban park. Moreover, the fraction of
      vanadium in each sequential extraction characterized that residual fraction >
      oxidizable fraction > reducible fraction > acid soluble fraction. The
      bioaccumulation of vanadium from soil to plant was weak to intermediate
      absorption. Therefore, some countermeasures such as soil monitoring and
      remediation should be to take in the sooner future, especially in mining and
      smelting area.

PMID- 20676934
TI  - Generation of transgenic plants expressing plasma membrane-bound antibodies to
      the environmental pollutant microcystin-LR.
AB  - In this paper we describe the engineering and regeneration of transgenic tobacco
      plants expressing a recombinant plasma membrane-retained antibody specific to
      microcystin-LR (MC-LR), the environmental toxin pollutant produced by
      cyanobacteria. The antibody was created by a genetic fusion of the antigen
      binding regions of the microcystin-specific single chain antibody, 3A8, with the
      constant regions from the murine IgG1kappa, Guy's 13, including a membrane
      retention sequence at the C-terminal end of the antibody heavy chain. The
      antibody produced in the leaves was shown to be functional by binding to MC-LR in
      an ELISA with antibody yields in transgenic plant leaves reaching a maximum of
      1.2 MUg g(-1) leaf f.wt (0.005% total soluble protein). Antibody-MC-LR complexes
      formed in leaves after addition of MC-LR to hydroponic medium around the roots of
      transgenic plant cultures.

PMID- 20676935
TI  - Cytochrome b5 null mouse: a new model for studying inherited skin disorders and
      the role of unsaturated fatty acids in normal homeostasis.
AB  - Microsomal cytochrome b (5) is a ubiquitous, 15.2 kDa haemoprotein implicated in
      a number of cellular processes such as fatty acid desaturation, drug metabolism,
      steroid hormone biosynthesis and methaemoglobin reduction. As a consequence of
      these functions this protein has been considered essential for life. Most of the
      ascribed functions of cytochrome b (5), however, stem from in vitro studies and
      for this reason we have carried out a germline deletion of this enzyme. We have
      unexpectedly found that cytochrome b (5) null mice were viable and fertile, with
      pups being born at expected Mendelian ratios. However, a number of intriguing
      phenotypes were identified, including altered drug metabolism, methaemoglobinemia
      and disrupted steroid hormone homeostasis. In addition to these previously
      identified roles for this protein, cytochrome b (5) null mice displayed skin
      defects closely resembling those observed in autosomal recessive congenital
      ichthyosis and retardation of neonatal development, indicating that this protein,
      possibly as a consequence of its role in the de novo biosynthesis of unsaturated
      fatty acids, plays a central role in skin development and neonatal nutrition.
      Results from fatty acid profile analysis of several tissues suggest that
      cytochrome b (5) plays a role controlling saturated/unsaturated homeostasis.
      These data demonstrate that regional concentrations of unsaturated fatty acids
      are controlled by endogenous metabolic pathways and not by diet alone.

PMID- 20676936
TI  - A novel method for signal detection of adverse drug reactions based on
      proportional reporting ratios.
AB  - OBJECTIVE: The proportional reporting ratio (PRR) is a statistical method for
      signal detection of adverse drug reactions (ADRs) based on unbalanced
      proportions. Although effective, this method only takes into account the
      proportional relation based on target adverse reactions and ignores the relation
      between a given ADR and the others for the same drug. Therefore, it is necessary
      to improve the calculation deviation in PRR. In this study, we developed a novel
      PRR (NPRR) method and compared it with the original PRR method for the purpose of
      a combined application of these two methods for ADR signal detection. METHODS:
      NPRR is also based on unbalanced proportions, in which the proportion for a given
      ADR is linked to a specific drug (or all other drugs), and then divided by the
      corresponding proportion for all other ADRs. RESULTS: Applying this method to the
      ADR data of Jiangsu Province, China in 2008 and 2009, we detected 3,021 signals.
      Compared with the PRR method, the sensitivity of our method is 0.99, the
      specificity is 0.97, and the Youden index is 0.96. CONCLUSION: NPRR is an
      excellent method supplementary to PRR. The combination of these two methods can
      reduce calculation deviation and detect ADRs more effectively.

PMID- 20676937
TI  - Wakame and Nori in restructured meats included in cholesterol-enriched diets
      affect the antioxidant enzyme gene expressions and activities in Wistar rats.
AB  - The effects of diets including restructured meats (RM) containing Wakame or Nori
      on total liver glutathione status, and several antioxidant enzyme gene
      expressions and activities were tested. Six groups of ten male growing Wistar
      rats each were fed a mix of 85% AIN-93 M diet and 15% freeze-dried RM for 35
      days. The control group (C) consumed control RM, the Wakame (W) and the Nori (N)
      groups, RM with 5% Wakame and 5% Nori, respectively. Animals on added cholesterol
      diets (CC, CW, and CN) consumed their corresponding basal diets added with
      cholesterol (2%) and cholic acid (0.4%). Alga and dietary cholesterol
      significantly interact (P < 0.002) influencing all enzyme expressions but not
      activities. The cholesterol supplement decreased most enzyme expression and
      activity. W-RM vs. C-RM increased (P < 0.05) expression of GPx, GR, Mn-SOD, and
      Cu,Zn-SOD and decreased that of catalase. N-RM vs. C-RM increased (P < 0.05)
      expression of catalase and Mn-SOD. GR activity increased in W-RM rats while SOD
      activity increased, but that of Se-GPx decreased in N animals. W-RM increased
      total and reduced glutathione and decreased the redox index. CN diet induced
      significantly lower plasma cholesterol levels (P < 0.001) than the CW diet. In
      conclusion, Nori-RM is a hypocholesterolemic food while Wakame-RM is an
      antioxidant food. This should be taken into account when including this kind of
      RM as potential functional foods in human.

PMID- 20676938
TI  - The use of the internet training course modality in the field of tissue banking:
      the International Atomic Energy Agency (IAEA)/National University of Singapore
      (NUS) experience.
AB  - The International Atomic Energy Agency (IAEA) promoted and supported an important
      training program for the training of tissue bank operators and medical doctors
      within its radiation and tissue banking program. The purpose of the program was
      to train an increase number of tissue bank operators and medical doctors in Asia
      and the Pacific, Latin America and Eastern Europe, that were working or were
      associated to a number of tissue banks established in these regions under the
      IAEA program during the 1980s, 1990s and 2000s. The National University of
      Singapore Tissue Bank was designated, in 1996, as the Regional Training Centre
      (RTC) for Asia and the Pacific region and later on, in 2002, as the International
      Training Centre (ITC) for the whole IAEA program. The National Atomic Energy
      Commission of Argentina and the Faculty of Medicine of the University of Buenos
      Aires were also designated, in 1999, as the Regional Training Centre for the
      Latin American region. The objective of the ITC was to train tissue banks
      operators and medical doctors from all over the world and the RTCs to train
      tissue bank operators and medical doctors mainly from the Asia and the Pacific
      and the Latin American regions. Since 1997, training of tissue bank operators and
      medical doctors were carried out using the modality of distance training courses.
      However, due to its limitation, this type of courses was transformed, in 2002, in
      an Internet training course modality, with the purpose to increase not only the
      number of participants but, at the same time to reduce, as much as possible, the
      costs associated with the organisation of these courses. Since November 1997, the
      number of training courses carried out in the RTCs established under the IAEA
      program was 14, eight of them under the Internet training course modality. The
      total number of students registered in these courses was 261 and the total number
      of students graduated was 166 for a rate of approval of 63.6%. The National
      University of Singapore and the Faculty of Medicine from the University of Buenos
      Aires are the academic institutions that provide the certificate/diploma to the
      graduated students.

PMID- 20676939
TI  - An improved curvilinear gradient method for parameter optimization in complex
      biological models.
AB  - Mathematical modeling is an often used approach in biological science which,
      given some understanding of a system, is employed as a means of predicting future
      behavior and quantitative hypothesis testing. However, as our understanding of
      processes becomes more in depth, the models we use to describe them become
      correspondingly more complex. There is a paucity of effective methods available
      for sampling the vast objective surfaces associated with complex multiparameter
      models while at the same time maintaining the accuracy needed for local
      evaluation of minima-all in a practical time period. We have developed a series
      of modifications to the curvilinear gradient method for parameter optimization.
      We demonstrate the power and efficiency of our routine through fitting of a 22
      parameter Markov state model to an electrophysiological recording of a cardiac
      ion channel. Our method efficiently and accurately locates parameter minima which
      would not be easily identified using the currently available means. While the
      computational overhead involved in implementing the curvilinear gradient method
      may have contributed to resistance to adopting this technique, the performance
      improvements allowed by our modifications make this an extremely valuable tool in
      development of models of complex biological systems.

PMID- 20676940
TI  - Reasons and outcomes of reoperative bariatric surgery for failed and complicated
      procedures (excluding adjustable gastric banding).
AB  - BACKGROUND: The rise of bariatric surgery has lead to an increasing number of
      reoperations for failed bariatric procedures. The reasons and types of these
      operations are varied in nature and remain to be defined. METHODS: A
      retrospective review of a prospectively collected database was conducted to
      identify patients who underwent laparoscopic revisional surgery for non-gastric
      banding-related bariatric procedures between 2001 and 2008. RESULTS: Of 384
      secondary bariatric operations, 151 reoperative procedures were performed. Twenty
      six vertical banded gastroplasties (17.2%), 2 mini-gastric bypasses (1.3%), 2 non
      divided bypasses (1.3%), 1 distal Roux-en-Y gastric bypass (RYGBP; 0.7%), and 2
      sleeve gastrectomies (1.3%) were converted to RYGBP. Three RYGBP (2%) and four
      jejunoileal bypass procedures (2.6%) were reversed secondary to malnutrition. One
      jejunoileal bypass (0.7%) and one biliopancreatic diversion (0.7%) underwent
      sleeve gastrectomies. Three pre-anastomotic rings were removed due to erosion
      (2%). Eleven pouch trimmings (7.3%), 16 redo gastrojejunostomies (10.6%), 5 redo
      jejunojejunostomies (3.3%), 36 remnant gastrectomies (23.8%), and 2 gastrogastric
      fistula takedowns (1.3%) were performed for pouch enlargements, strictures, and
      gastrogastric fistulas. Thirty-six patients (23.8%) underwent a combination of
      these procedures. The major morbidity (13.2%) was related to leaks. Other
      complications included wound infection, intra-abdominal abscess formation, and
      trocar site hernias. The mortality rate was 2%. CONCLUSIONS: Reoperative
      bariatric surgery is a complex and growing field in bariatric surgery. The
      indications for surgical reoperation can vary depending on the procedure and
      reason for intervention. Laparoscopy appears to be a feasible approach. Though
      safe, morbidity and mortality are significantly higher than in primary bariatric
      procedures.

PMID- 20676941
TI  - Topological determination of early morphogenesis in Metazoa.
AB  - This paper presents a topological interpretation of some developmental events
      through the use of well-known concepts and theorems of combinatorial geometry.
      The organization of early embryo using a simulation of cleavage considering only
      blastomere contacts is examined. Each blastomere is modeled as a topological cell
      and whole embryo--as cell packing. The egg cleavage results in a pattern of
      cellular contacts on the surface of each blastomere and whole embryo, a discrete
      morphogenetic field. We find topological distinctions between different types of
      early egg cleavage and suggest a topological classification of cleavage.
      Blastulation and gastrulation may be related to an inevitable emergence of
      discrete curvature that directs development in three-dimensional space. The
      relationship between local and global orders in metazoan development, i.e.,
      between local morphogenetic processes and integral developmental patterns, is
      established. Thus, this methodology reveals a topological imperative: a certain
      set of topological rules that constrains and directs biological morphogenesis.

PMID- 20676942
TI  - Unveiling hair follicle stem cells.
AB  - Adult mammalian skin consists of the epidermis, hair follicles (HFs), and
      sebaceous glands (SGs). Each of these three epithelial lineages contains its own
      stem cell (SC) population for normal tissue homeostasis, HF cycling, and repair
      of the epidermis following injury. Here, we provide an overview of the current
      knowledge on follicle SCs of the adult skin, including their essential features
      and, most importantly, the control of follicle SC fate. Wnt/beta-catenin is
      required for follicle SC maintenance and niche biology, and beta-catenin
      activation is essential for promoting quiescent follicle SCs to proliferate and
      terminally differentiate along the hair cell lineage. Further, beta-catenin
      stabilization promotes de novo HF morphogenesis, and constitutively active beta
      catenin expression results in pilomatricoma. Both bone morphogenetic protein
      (BMP) and transforming growth factor-beta (TGF-beta) signals are required for
      quiescent niche maintenance: BMP deletion results in SC activation, whereas TGF
      beta may play a role in SC identity maintenance.

PMID- 20676944
TI  - Treatment of preschoolers with attention-deficit/hyperactivity disorder.
AB  - This article reviews the current treatment literature for attention
      deficit/hyperactivity disorder (ADHD) in preschoolers. Parent training studies
      show consistent behavioral improvements reported by teachers and observers as
      well as parents, with evidence of clinically significant improvement in ADHD
      symptoms for up to 2 years. Few other behavioral interventions have been
      evaluated, although data from a large psychosocial, multimodal intervention are
      forthcoming. There is evidence to support the benefit of immediate-release
      stimulant medication for up to 1 year; however, effects do not seem to be as
      large, and some of the side effects may be greater than for school-age children.
      With regard to nonstimulants such as atomoxetine, there are literally no
      controlled outcome data for children with ADHD who are younger than 5 years of
      age. Overall, a great deal remains to be learned about the safety and efficacy of
      pharmacotherapy in this age group. Fortunately, results of several large
      intervention studies will be available soon to better inform clinical practice.

PMID- 20676943
TI  - Therapeutic potentials of mesenchymal stem cells derived from human umbilical
      cord.
AB  - Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs), isolated from
      discarded extra-embryonic tissue after birth, are promising candidate source of
      mesenchymal stem cells (MSCs). Apart from their prominent advantages in abundant
      supply, painless collection, and faster self-renewal, hUC-MSCs have shown the
      potencies to differentiate into a variety of cells of three germ layers (such as
      bone, cartilage, adipose, skeletal muscle, cardiomyocyte, endothelium, hepatocyte
      like cluster, islet-like cluster, neuron, astrocyte and oligodendrocyte), to
      synthesize and secret a set of trophic factors and cytokines, to support the
      expansion and function of other cells (like hematopoietic stem cells, embryonic
      stem cells, natural killer cells, islet-like cell clusters, neurons and glial
      cells), to migrate toward and home to pathological areas, and to be readily
      transfected with conventional methods. Two excellent previous reviews documenting
      the characteristics of this cell population with special emphasis on its niche,
      isolation, surface markers and primitive properties have been published recently.
      In this review, we will firstly give a brief introduction of this cell
      population, and subsequently dwell on the findings of differential capacities
      with emphasis on its therapeutic potentials.

PMID- 20676946
TI  - Parallel thermal analysis technology using an infrared camera for high-throughput
      evaluation of active pharmaceutical ingredients: a case study of melting point
      determination.
AB  - Various techniques for physical characterization of active pharmaceutical
      ingredients, including X-ray powder diffraction, birefringence observation, Raman
      spectroscopy, and high-performance liquid chromatography, can be conducted using
      96-well plates. The only exception among the important characterization items is
      the thermal analysis, which can be a limiting step in many cases, notably when
      screening the crystal/salt form. In this study, infrared thermal camera
      technology was applied for thermal characterization of pharmaceutical compounds.
      The melting temperature of model compounds was determined typically within 5 min,
      and the obtained melting temperature values agreed well with those from
      differential scanning calorimetry measurements. Since many compounds can be
      investigated simultaneously in this infrared technology, it should be promising
      for high-throughput thermal analysis in the pharmaceutical developmental process.

PMID- 20676945
TI  - Brain imaging studies in pathological gambling.
AB  - This article reviews the neuroimaging research on pathological gambling (PG).
      Because of the similarities between substance dependence and PG, PG research has
      used paradigms similar to those used in substance use disorder research, focusing
      on reward and punishment sensitivity, cue reactivity, impulsivity, and decision
      making. This review shows that PG is consistently associated with blunted
      mesolimbic-prefrontal cortex activation to nonspecific rewards, whereas these
      areas show increased activation when exposed to gambling-related stimuli in cue
      exposure paradigms. Very little is known, and hence more research is needed
      regarding the neural underpinnings of impulsivity and decision making in PG. This
      review concludes with a discussion regarding the challenges and new developments
      in the field of neurobiological gambling research and comments on their
      implications for the treatment of PG.

PMID- 20676948
TI  - [In-hospital resuscitation concept with first-responder defibrillation. 2-year
      experience].
AB  - BACKGROUND AND PURPOSE: Sudden cardiac arrest appears in 1-5 patients/ 1,000
      clinical admissions. In spite of different research approaches, the prognosis
      after in-hospital resuscitation has not significantly improved in the last 40
      years. This account presents the experiences with a hospital-wide emergency plan
      using the concept of defibrillation by first responders. METHODS: In 2003, a
      hospital-wide emergency plan was implemented. The concept comprised the setup of
      15 "defibrillator points", training of the entire hospital personnel as first
      responder, and the introduction of an emergency team. Over the following 3 years,
      the concept was optimized. In a period from May 2006 to April 2008, the data of
      all patients who received an in-hospital resuscitation were collected. RESULTS:
      Within 24 months, a total of 41 resuscitations were conducted. Out of these, 24
      patients (58%) were under intensive monitoring when the event occurred.
      Initially, 15 patients (36%) showed ventricular fibrillation, 15 (36%) a
      pulseless electrical activity, and eleven (27%) an asystoly. A total of twelve
      patients (29%) left hospital alive. About half of them (42%) experienced
      ventricular fibrillation and were under observation at the time of event.
      CONCLUSION: The data collected since the implementation of the hospital- wide
      emergency plan in 2003 reflect the daily clinical routine. The results show that
      there is a better outcome especially in patients with ventricular fibrillation
      when receiving first-responder defibrillation.

PMID- 20676947
TI  - Formulation of microneedles coated with influenza virus-like particle vaccine.
AB  - Mortality due to seasonal and pandemic influenza could be reduced by increasing
      the speed of influenza vaccine production and distribution. We propose that
      vaccination can be expedited by (1) immunizing with influenza virus-like particle
      (VLP) vaccines, which are simpler and faster to manufacture than conventional egg
      based inactivated virus vaccines, and (2) administering vaccines using
      microneedle patches, which should simplify vaccine distribution due to their
      small package size and possible self-administration. In this study, we coated
      microneedle patches with influenza VLP vaccine, which was released into skin by
      dissolution within minutes. Optimizing the coating formulation required balancing
      factors affecting the coating dose and vaccine antigen stability. Vaccine
      stability, as measured by an in vitro hemagglutination assay, was increased by
      formulation with increased concentration of trehalose or other stabilizing
      carbohydrate compounds and decreased concentration of carboxymethylcellulose
      (CMC) or other viscosity-enhancing compounds. Coating dose was increased by
      formulation with increased VLP concentration, increased CMC concentration, and
      decreased trehalose concentration, as well as increased number of dip coating
      cycles. Finally, vaccination of mice using microneedles stabilized by trehalose
      generated strong antibody responses and provided full protection against high
      dose lethal challenge infection. In summary, this study provides detailed
      analysis to guide formulation of microneedle patches coated with influenza VLP
      vaccine and demonstrates effective vaccination in vivo using this system.

PMID- 20676949
TI  - [New drugs for the treatment of constipation].
AB  - This review introduces new therapeutic options in the treatment of chronic
      idiopathic constipation and irritable bowel syndrome with constipation.
      Therefore, prucalopride and lubiprostone are discussed including their mechanisms
      and side effects. In addition, other substances that are currently under
      evaluation such as renzapride and linaclotide are described, since recent results
      showed a significant effect in patients with constipation. Thus, after the
      withdrawal of tegaserod due to cardiac side effects, new potent drugs are now
      available for the treatment of constipation.

PMID- 20676950
TI  - [Psychosomatic aspects of cardiac arrhythmias].
AB  - Emotional stress facilitates the occurrence of cardiac arrhythmias including
      sudden cardiac death. The prevalence of anxiety and depression is increased in
      cardiac patients as compared to the normal population. The risk of cardiovascular
      mortality is enhanced in patients suffering from depression. Comorbid anxiety
      disorders worsen the course of cardiac arrhythmias. Disturbance of neurocardiac
      regulation with predominance of the sympathetic tone is hypothesized to be
      causative for this. The emotional reaction to cardiac arrhythmias is differing to
      a large extent between individuals. Emotional stress may result from coping with
      treatment of cardiac arrhythmias. Emotional stress and cardiac arrhythmias may
      influence each other in the sense of a vicious circle. Somatoform cardiac
      arrhythmias are predominantly of psychogenic origin. Instrumental measures and
      frequent contacts between physicians and patients may facilitate disease
      chronification. The present review is dealing with the multifaceted relationships
      between cardiac arrhythmias and emotional stress. The underlying mechanisms and
      corresponding treatment modalities are discussed.

PMID- 20676951
TI  - [Autoimmune thyroiditis (Hashimoto's thyroiditis): current diagnostics and
      therapy].
AB  - Hashimoto's thyroiditis is a common autoimmune thyroid disease with preference of
      female gender. The chronic thyroiditis is characterized by autoantibodies against
      thyroid peroxidase and thyroglobulin. With manifestation, there is often a
      subclinical hypothyroidism that finally progresses to a persistent hypothyroidism
      with typical clinical symptoms and the need of hormonal substitution in
      succession of the lymphocytic infiltration of the thyroid. The ultrasound of the
      thyroid shows a hypoechogenic and inhomogeneous parenchyma. Autoimmune
      thyroiditis is frequently associated with autoimmune disease of other organs,
      such as vitiligo, Addison's disease, diabetes mellitus type 1, often in the sense
      of polyglandular syndrome 2.

PMID- 20676952
TI  - [Pareses, myalgias, and massive CK elevation: a severe neurological disorder?].
AB  - CASE REPORT: The authors report on a 51-year-old patient with transient pareses,
      myalgias, and a massive creatine kinase elevation which had led to an intensive
      neurological work-up by the general practitioner. Despite refractory
      hypertension, primary aldosteronism was not excluded. At the authors' clinic, the
      patient was diagnosed to have Conn's syndrome. Laparoscopic adrenalectomy
      revealed a big adenoma of the left adrenal gland. CONCLUSION: Transient pareses,
      myalgias, and creatine kinase elevation can indicate primary aldosteronism among
      hypertensive patients. If clinically suspected, the aldosterone-renin ratio
      should be determined.

PMID- 20676953
TI  - [Targeted diagnosis of basilar artery thrombosis].

PMID- 20676956
TI  - Apelin: a novel marker for the patients with first ST-elevation myocardial
      infarction.
AB  - To date, only animal studies have been concerned with apelin involvement in acute
      myocardial ischemia. The aim of this study was to investigate apelin measurements
      in low-risk patients with first ST-elevation myocardial infarction (STEMI) and to
      assess if apelin may feature as a marker of left ventricular (LV) injury and
      prognosis. In 78 consecutive patients (mean age 67 +/- 11.5 years, 24 women) with
      first STEMI treated with primary percutaneous coronary intervention, plasma
      apelin-36 concentrations were measured twice: on admission and on the 5th day of
      hospitalization. Left ventricle ejection fraction (LVEF) was applied as marker of
      LV injury. Composite endpoint (CEP), which included death, stroke, and recurrent
      ischemic event, was assessed after 1 year follow-up. On the first day, median
      apelin-36 concentration was 2138.5 pg/ml and on the 5th day was significantly
      lower, 2008.3 pg/ml (P = 0.002). There were no significant differences found in
      apelin-36 concentrations between patients with normal and low LVEF. In both
      groups significant reductions were found in apelin-36 concentrations measured in
      5-day intervals (P = 0.04 and P = 0.008, respectively). After a 1-year follow-up,
      only one patient died and 19 patients (24.3%) had reached CEP. No difference in
      baseline apelin-36 concentrations were found in the group of patients who reached
      CEP compared with those without CEP. However, in both groups concentrations
      significantly decreased after 5 days (P = 0.04 and P = 0.013, respectively).
      Apelin-36 concentrations are reduced in low risk first STEMI patients during the
      first days regardless of the degree of LV dysfunction and prognosis.

PMID- 20676957
TI  - Two single nucleotide polymorphisms in ALOX15 are associated with risk of
      coronary artery disease in a Chinese Han population.
AB  - Arachidonate 12/15-lipoxygenase (12/15-LOX) has been implicated in the
      pathogenesis of atherosclerosis, but with contradicting results. The aim of this
      study was to investigate the association of two polymorphisms in ALOX15 and the
      risk of coronary artery disease (CAD) in a Chinese Han population. A total of 519
      unrelated CAD patients and 608 unrelated control subjects of the Chinese Han
      population were recruited in the case-control study. Two tagSNPs, rs7217186:T>C
      and rs2619112:G>A, were selected and genotyped by polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP). The carriers of the C allele
      (the CC homozygote and the CT heterozygote) of rs7217186:T>C and the carriers of
      the A allele (the AA homozygote and the GA heterozygote) of rs2619112:G>A
      displayed elevated odds ratios (ORs) for CAD compared with the TT homozygotes and
      GG homozygotes, respectively, after adjusting for other potential confounders
      including age, sex, body mass index, systolic blood pressure, diastolic blood
      pressure, glucose, triglyceride, total cholesterol, high-density lipoprotein
      cholesterol, low-density lipoprotein cholesterol, and smoking status (adjusted
      odds ratio [OR] = 3.2, 95% confidence interval [CI]: 1.335-7.665, P = 0.009 and
      adjusted OR = 3.5, 95% CI: 1.343-9.330, P = 0.011). In stratified analyses, after
      adjusting those aforementioned confounders, the CC and CT genotypes of
      rs7217186:T>C were associated with a greater risk of CAD in subjects <60 years
      (adjusted OR = 5.7, 95% CI: 1.557-21.097, P = 0.009) and in females (adjusted OR
      = 9.3, 95% CI: 1.048-82.213, P = 0.045). For rs2619112:G>A, subjects (<60 years)
      carrying the A allele had a greater risk of CAD than the GG homozygotes (adjusted
      OR = 4.9, 95% CI: 1.215-19.547, P = 0.025); the male carriers of A allele also
      had a greater risk (adjusted OR = 3.5, 95% CI: 1.136-11.006, P = 0.029). In
      summary, the present study shows that after adjustment for other confounding CAD
      factors, rs7217186:T>C and rs2619112:G>A of ALOX15 are associated with increased
      risk of CAD in this Chinese Han population.

PMID- 20676958
TI  - Prolonged pain to hospital time is associated with increased plasma advanced
      oxidation protein products and poor prognosis in patients with percutaneous
      coronary intervention for ST-elevation myocardial infarction.
AB  - Plasma advanced oxidation protein products (AOPP) are a biomarker for increased
      production of reactive oxygen species. We examined the possible association
      between pain to hospital time, plasma AOPP, and outcome of patients receiving
      percutaneous coronary intervention (PCI) for ST-elevation acute myocardial
      infarction (STEMI). Plasma AOPP was determined at hospitalization as well as 24
      and 48 h after PCI in 79 patients with suspected STEMI. Patients were stratified
      into a control group (Group I, n = 21) after exclusion of coronary artery
      disease, Group II (n = 46) with pain to hospital time <12 h, and Group III (n =
      33) with pain to hospital time >12 h. Associations between pain to hospital time
      and AOPP as well as incidence of major adverse cardiac events (MACE) during 6
      months of follow-up were analyzed. Plasma AOPP at admission was significantly
      higher in patients of Group II (97.58 +/- 23.41 micromol/l) and Group III (184.52
      +/- 30.41 micromol/l) in comparison with Group I (57.41 +/- 13.60 micromol/l, all
      P < 0.001). Plasma AOPP concentration was positively correlated with pain to
      hospital time and associated with an increased incidence of MACE during the 6
      month follow-up period. Prolonged ischemia is associated with increased oxidative
      stress and poor prognosis in patients treated with PCI for STEMI.

PMID- 20676959
TI  - Scavenging free radicals improves endothelial dysfunction in human coronary
      arteries in vivo.
AB  - The effect of a novel free radical scavenger, edaravone, on coronary endothelial
      dysfunction was examined in patients who had no significant stenosis of coronary
      arteries, to elucidate the role of free radicals on coronary endothelial
      dysfunction. The coronary blood flow (CBF) responses to acetylcholine (ACh) were
      measured by quantitative coronary arteriography and the intracoronary Doppler
      technique before and after the administration of edaravone. Twenty-four patients
      were divided into two groups on the basis of CBF responses to ACh; those with
      "attenuated" (%Delta CBF < 300%, n = 12) and "normal" (%Delta CBF > 300%, n = 12)
      flow responses. An intracoronary infusion of edaravone significantly improved ACh
      induced increases in CBF in patients with attenuated flow responses; however,
      edaravone had no effect in those with normal flow responses (36.8% +/- 7.3% vs
      0.0% +/- 5.1%, P < 0.01). The plasma levels of nitric oxide compounds (NOx) in
      the attenuated response group were lower than those in the normal group (35.7 +/-
      2.3 vs 49.4 +/- 6.2 muM, P < 0.01) and correlated with the magnitude of CBF
      improvement by edaravone (r = 0.566, P < 0.01). The plasma level of
      malondialdehyde and 4-hydroxynonenal, which indicates the level of oxidative
      stress, in the attenuated group was higher than that in the normal group (6.9 +/-
      0.9 vs 3.3 +/- 0.5 muM, P < 0.01) and correlated with the magnitude of CBF
      improvement by edaravone (r = 0.854, P < 0.01). A free radical scavenger improved
      the ACh-induced CBF response in patients with coronary atherosclerosis in vivo.
      Therefore, the current results suggest that scavenging free radicals has a
      beneficial effect for patients with coronary endothelial dysfunction.

PMID- 20676960
TI  - Increased C-reactive protein is associated with future development of diabetes
      mellitus in essential hypertensive patients.
AB  - Coexistence of hypertension and diabetes mellitus (DM) increases the risk of
      cardiovascular disease. However, factors associated with future development of DM
      have not been well elucidated in patients already having essential hypertension.
      This study prospectively included 168 patients (mean age 41 +/- 7 years, 112 men)
      with essential hypertension. All patients did not have DM and vascular or renal
      complications initially. Baseline demographic data, blood pressure, body mass
      index, and antihypertensive agents were carefully evaluated and serum high
      sensitivity C-reactive protein (hsCRP) was measured at the beginning of the
      study. All of the patients were followed for at least 6 months. The study
      endpoint was occurrence of new DM. After a mean follow-up period of 32 +/- 10
      months, 22 subjects (13.1%) developed new DM. Patients with new DM had higher
      baseline glucose (105.2 +/- 11.8 vs 94.2 +/- 8.0 mg/dl, P < 0.001), triglyceride
      level (213.7 +/- 112.4 vs 155.6 +/- 83.2 mg/dl, P = 0.04), log hsCRP (0.31 +/-
      0.44 vs 0.19 +/- 0.25 mg/dl, P = 0.016), and lower high-density lipoprotein (40.2
      +/- 7.8 vs 46.6 +/- 14.4 mg/dl, P = 0.045). Total cholesterol, low-density
      lipoprotein, homeostasis model assessment index, and adiponectin were not
      different in patients with or without new DM. Among antihypertensive agents, only
      use of beta-blocker was significantly associated with new DM (P = 0.008).
      Multivariate Cox regression analysis showed log hsCRP (hazard ratio [HR] 9.77,
      95% confidence interval [CI] 2.97-32.10, P < 0.001), age (HR 1.21, 95% CI 1.06
      1.38, P = 0.004), and baseline glucose level (HR 1.11, 95% CI 1.06-1.15, P <
      0.001) to be independent predictors for occurrence of new DM. High-sensitivity
      CRP was an independent factor for future development of DM in essential
      hypertensive patients. Increased inflammation might have a key role in the
      pathogenesis of DM in hypertension.

PMID- 20676961
TI  - Short-term effect of levosimendan on free light chain kappa and lambda levels in
      patients with decompensated chronic heart failure.
AB  - To investigate the effects of levosimendan, a positive inotropic agent, on the
      new heart failure markers immunoglobulin free light chains kappa and lambda (FLC
      kappa and FLC-lambda) in decompensated chronic heart failure (HF), 59 patients
      with New York Heart Association (NYHA) class III-IV HF were enrolled. Patients
      were randomized into levosimendan (n = 31) and standard HF treatment (n = 29)
      groups. Serum FLC-kappa and FLC-lambda, brain natriuretic peptide (BNP), and
      ejection fraction (EF) were measured before treatment and on the 5th day of
      treatment initiation. Forty-two percent of subjects were females (n = 25) and
      overall mean age was 64.1 +/- 10.7 years. FLC-kappa (P < 0.05) and FLC-lambda (P
      < 0.05) were significantly decreased in the levosimendan group compared to
      baseline, but no difference in either marker in the standard treatment group was
      observed. Pre- and post-treatment FLC-kappa/FLC-lambda ratios in both groups were
      similar, whereas FLC-kappa and FLC-lambda levels and the FLC-kappa/FLC-lambda
      ratio showed no significant correlation with NYHA class, brain natriuretic
      peptide (BNP) and ejection fraction (EF) levels; and BNP and EF changes after the
      treatment. Symptomatic improvement in the levosimendan group according to the
      NYHA class was significantly better than in the standard treatment group (P =
      0.044). While 55.2% of patients in the levosimendan group showed a 1-degree shift
      to lower NYHA classes, 10.3% showed a 2-degree decrease. In conclusion,
      levosimendan caused short-term hemodynamic and symptomatic improvements, with a
      more pronounced decrease in FLC levels in patients with advanced decompensated
      HF.

PMID- 20676962
TI  - Influence of obstructive sleep apnea on left ventricular mass and global
      function: sleep apnea and myocardial performance index.
AB  - Obstructive sleep apnea (OSA) is associated with cardiovascular mortality and
      morbidity. It may predispose patients to left ventricular hypertrophy and heart
      failure. The aim of this study was to determine the left ventricular mass (LVM)
      and myocardial performance index (MPI) reflecting left ventricular global
      function in uncomplicated OSA patients. Sixty-four subjects without hypertension,
      diabetes mellitus, and any cardiac or pulmonary disease referred for evaluation
      of OSA underwent overnight polysomnography and complete echocardiographic
      assessment. According to the apnea hypopnea index (AHI), subjects were divided
      into three groups: group 1, control subjects with nonapneic snorers (AHI < 5, n =
      18); group 2, patients with mild to moderate OSA (AHI: 5-30, n = 25); and group
      3, severe OSA (AHI > 30, n = 21). Basic echocardiographic measurements, LVM, and
      LVM index were measured. Left ventricular MPI was calculated as (isovolumic
      contraction time+isovolumic relaxation time)/aortic ejection time by Doppler
      echocardiography. There were no significant differences in age, sex, body mass
      index, heart rate, and systolic and diastolic blood pressure among the three
      groups. Left atrium, interventricular septum, left ventricular posterior wall,
      left ventricular end-diastolic and end-systolic diameters, LVM mass, and LVM
      index were not significantly different among the three groups. Left ventricular
      MPI was significantly higher in severe OSA patients (0.64 +/- 0.18) than in
      controls (0.49 +/- 0.18; P < 0.05). There was no significant difference between
      controls (0.49 +/- 0.18) and mild to moderate OSA (0.61 +/- 0.16; P = 0.08) and
      between mild to moderate OSA (0.61 +/- 0.16) and severe OSA (0.64 +/- 0.18; P =
      0.84). The present study demonstrates that patients with severe OSA have global
      left ventricular dysfunction.

PMID- 20676963
TI  - Risk factors for acute shunt blockage in children after modified Blalock-Taussig
      shunt operations.
AB  - Factors relating to acute blockage of modified Blalock-Taussig shunts (MBTS) have
      not been well described in the literature. Our aim was to determine the outcomes
      in patients early after undergoing MBTS operations and to identify potential risk
      factors for acute shunt blockage in the early postoperative period. A
      retrospective study was performed in a tertiary referral congenital cardiac unit.
      All children who underwent first shunt insertion for cyanotic congenital heart
      disease during the study period from 2002 to 2006 were included. Seventy-six
      children underwent first shunt insertion with a median age of 37 days (range 2
      days-8 years) and median weight of 3.75 kg (range 2.1-17.2 kg). The shunt sizes
      varied from 3 to 6 mm. The rate of acute shunt blockage was 11.8% (9/76), all
      within the first 24 h. There were 3 early deaths (3.9%), none of which were
      associated with shunt blockage. The main risk factors for blockage were
      preoperative high hemoglobin, weight less than 3 kg, and duct patency on
      echocardiogram after surgery. This study identifies that high preoperative
      hemoglobin, a weight less than 3 kg at operation, and the presence of a patent
      duct are statistically significant risk factors for shunt blockage in the acute
      postoperative period. Further work is needed to determine if reduction in
      preoperative hemoglobin concentration and attempts to reduce postoperative ductal
      patency may alter the outcome.

PMID- 20676964
TI  - Relation of gender and interatrial dyssynchrony on tissue Doppler imaging to the
      prediction of the progression to chronic atrial fibrillation in patients with
      nonvalvular paroxysmal atrial fibrillation.
AB  - This prospective study aimed to identify the relation of gender and interatrial
      dyssynchrony on tissue Doppler imaging (TDI) to the prediction of the progression
      to chronic atrial fibrillation (CAF) in nonvalvular paroxysmal AF (PAF) patients.
      Nineteen consecutive men and 19 women with nonvalvular PAF were prospectively
      followed after echocardiography. We measured the interval of time from initiation
      of the P wave on the electrocardiogram until the beginning of the late diastolic
      TDI signal at the lateral border of the mitral (P-A'(M)) and the tricuspid
      annulus (P-A'(T)). Interatrial dyssynchrony was defined as the difference between
      the P-A'(M) and P-A'(T) intervals (A'(M)-A'(T)). The study endpoint was the onset
      of CAF (>6 months). Six men developed CAF during a follow-up of 32 +/- 26 months,
      and 3 women developed CAF during a follow-up of 25 +/- 19 months. Compared to
      those without CAF, the patients with CAF had significantly longer A'(M)- A'(T)
      intervals (men: 41 +/- 10 vs 27 +/- 12 ms, women: 64 +/- 4 vs 23 +/- 9 ms; P <
      0.01) in both genders. Kaplan-Meier analysis, using cutoff values determined by
      analysis of receiver-operating characteristics curves, revealed that the
      progression to CAF was significantly observed more often when A'(M)-A'(T)
      interval was >34 ms in men and >43 ms in women. This prospective study suggests
      that nonvalvular PAF men and women with a high risk of developing CAF have
      "interatrial dyssynchrony" on atrial TDI, whose cutoff values are shorter and may
      affect the vulnerability of AF in men.

PMID- 20676965
TI  - Severe, short-term food restriction improves cardiac function following
      ischemia/reperfusion in perfused rat hearts.
AB  - The purpose of this study was to clarify the characteristics of improved ischemic
      tolerance induced by severe, short-term food restriction in isolated, perfused
      rat hearts. Male Wistar (8 week-old) rats were given a food intake equivalent to
      a 70% reduction on the food intake of ad-libitum fed rats for 11 days (FR group
      and AL group, respectively). After this period, hearts were isolated and perfused
      in the Langendorff mode, and subjected to 20 min of global ischemia followed by
      30 min of reperfusion. Although the coronary flow rate in the FR group (63.0 +/-
      3.1 ml/min/g dry weight) was higher than that in the AL group (47.1 +/- 1.3
      ml/min/g dry weight) during preischemic perfusion, the lactate release into the
      coronary effluent and absolute values of +dP/dt and -dP/dt in the FR group (2422
      +/- 161 and -1282 +/- 51) were inversely lower than in the AL group (2971 +/- 156
      and -1538 +/- 74, respectively). An increase in ischemic contracture was
      suppressed in the FR group. Following reperfusion, cardiac function, high-energy
      phosphate content, and intracellular pH, as measured by 31P-nuclear magnetic
      resonance spectroscopy, had recovered to a much greater degree in the FR group
      than in the AL group. The serum T3 level was significantly lower in the FR group
      (2.7 +/- 0.1 pg/ml) than in the AL group (3.6 +/- 0.1 pg/ml), and the levels of
      triglycerides, free fatty acids, insulin, and glucose were also significantly
      lower in the FR group than in the AL group. The protein expressions of myocyte
      enhancer factor 2A, Na(+), K(+)-ATPase, and phospholamban in the cardiac tissue
      were higher in the FR group than in the AL group. These results suggested that
      severe, short-term food restriction improves ischemic tolerance in rat hearts via
      altered expression of functional proteins induced by low serum T3 levels,
      decreased coronary conductance, and change in metabolic flux.

PMID- 20676966
TI  - On the combined effect of statins and lycopene on cytokine production by human
      peripheral blood cells.
AB  - Since both statins and lycopene exert immunomodulatory activities following
      incubation with human peripheral blood mononuclear cells (PBMC), the present work
      was designed to examine whether they may induce a synergistic or antagonistic
      effect on cytokine production while applied together. Peripheral blood
      mononuclear cells isolated from 15 healthy subjects were incubated for 24 h as
      follows: (1) without and with 0.125 or 0.25 microM lycopene, (2) without and with
      10 or 50 mM pravastatin or simvastatin, and (3) with lycopene and with one of the
      statins together at the respective doses. The production of the following
      cytokines was assessed: interleukin (IL)-1beta, IL-1ra, IL-2, and IL-10, as well
      as tumor necrosis factor alpha (TNFalpha) and interferon gamma (IFNgamma). The
      results showed that lycopene and simvastatin applied together reduced TNFalpha
      and IFNgamma secretion, and abolished the increased production of the
      proinflammatory cytokine IL-1gamma caused by incubation with simvastatin only, an
      observation suggesting that simultaneous administration of both substances may
      reduce inflammatory responses.

PMID- 20676967
TI  - Dopamine receptor subtypes in the native human heart.
AB  - The present study first time detected D1-D5 dopamine receptor subtypes in the
      native human heart simultaneously, found presence of D1, D2, D4, and D5 in
      cardiac tissues, and revealed distribution features of dopamine receptor subtypes
      in the epicardium, myocardium, and endocardium. Samples from four native hearts
      coming from young brain-dead donors, which for technical reason were not used for
      transplants, were studied. Dopamine receptors were revealed by immunochemistry
      technique and immunoblot analysis. Morphometrical quantification of the density
      of each receptor subtype was performed by an image analyzer. Our results
      demonstrate that only four subtypes of dopamine receptors can be found in cardiac
      tissues: D1, D2, D4, and D5. These dopamine receptors have been detected in
      endocardium, myocardium, and epicardium. D1 receptors were stored primarily in
      the epicardial layer. Dopamine receptors are distributed in the wall of both
      atria and ventricles, and its transmural gradient can be described in the wall of
      the human heart. Sections of atria and ventricles exposed to antidopamine
      receptor antibodies showed fluorescent-positive reaction in the epicardium,
      myocardium and endocardium. D4 receptor immune reactivity was remarkably less
      intense than D2 receptor immune reactivity. All the subtypes of dopamine
      receptors are in close relationships with all cardiac structures. Our findings
      provide a favorable basis for researching the role of dopamine receptors in
      controlling functions of the human heart and in the pathogenesis of
      cardiovascular diseases.

PMID- 20676968
TI  - The nonpeptide AVE0991 attenuates myocardial hypertrophy as induced by
      angiotensin II through downregulation of transforming growth factor-beta1/Smad2
      expression.
AB  - The nonpeptide AVE0991 is expected to be a putative new drug for cardiovascular
      diseases. However, the mechanisms for the cardioprotective actions of AVE0991 are
      still not fully understood. We planned to determine whether AVE0991 attenuates
      the angiotensin II (AngII)-induced myocardial hypertrophy and whether these
      AVE0991 effects involved transforming growth factor beta1 (TGF-beta1) and Smad2.
      A rat model of neonatal myocardial hypertrophy was induced by AngII. The AngII
      group significantly increased in protein content, surface area, and [(3)H]leucine
      incorporation efficiency by cardiomyocytes, compared to those of the control
      group (P < 0.01). The AngII group also had elevated TGF-beta1 and Smad2
      expression (P < 0.01). These AngII-induced changes were significantly attenuated
      by AVE0991 in a dose-dependent manner. In our study, these actions of AngII (10(
      6) mol/l) were significantly inhibited by both concentrations of AVE0991 (10(-5)
      mol/l and 10(-7) mol/l). Moreover, the high AVE0991 group had significantly
      better inhibition of myocardial hypertrophy than the low AVE0991 group.
      Meanwhile, the beneficial effects of AVE0991 were completely abolished when the
      cardiomyocytes were pretreated with Ang-(1-7) receptor antagonist A-779 (10(-6)
      mol/l). These results suggested that AVE0991 prevented AngII-inducing myocardial
      hypertrophy in a dose-dependent fashion, a process that may be associated with
      the inhibition of TGF-beta1/Smad2 signaling.

PMID- 20676970
TI  - Clinical effectiveness of pulmonary vein isolation for arrhythmic events in a
      patient with catecholaminergic polymorphic ventricular tachycardia.
AB  - An 18-year-old woman with catecholaminergic polymorphic ventricular tachycardia
      (CPVT) underwent pulmonary vein isolation (PVI) because of frequent and
      inappropriate shocks from an implantable cardioverter defibrillator (ICD)
      associated with atrial fibrillation (AF) with a rapid ventricular response. While
      the PVI did not completely suppress the AF induced by an isoproterenol infusion,
      the Holter monitor recordings demonstrated a major decrease in the clinical
      episodes of AF and ventricular tachyarrhythmias in association with a reduced
      high-frequency (HF) component and ratio of the low-frequency (LF) component power
      to the HF component (LF/HF) after the PVI. The PVI can decrease the substrates
      that trigger and maintain the AF when it involves a pulmonary vein origin, and
      may exert an additional effect on the sympathetic nerve input to the heart. The
      PVI may be an adjunctive therapy for CPVT cases with drug refractory AF causing
      inappropriate ICD discharges.

PMID- 20676969
TI  - The efficacy of tocilizumab in a patient with pulmonary arterial hypertension
      associated with Castleman's disease.
AB  - Castleman's disease is a highly heterogeneous clinical-pathological entity that
      belongs to the lymphoproliferative disorders and is associated with pulmonary
      arterial hypertension (PAH) in some patients. It is linked to excessive immune
      stimulation by interleukin-6 (IL-6), which is also involved in the pathogenesis
      of PAH. A 31-year-old woman with Castleman's disease demonstrated PAH
      characterized by severe right heart failure. Since she was resistant to various
      conventional therapies including steroids, prostacyclins, bosentan, and
      sildenafil, tocilizumab (anti-IL-6 receptor antibody) therapy was started. Her
      clinical course was followed for 6 months, with significant improvement without
      any adverse effect. This is the first reported case of use of tocilizumab in
      addition to steroids and conventional PAH therapy in a patient with PAH
      associated with Castleman's disease.

PMID- 20676971
TI  - Small molecule inhibitors of the human papillomavirus E1-E2 interaction.
AB  - Human papillomaviruses are responsible for multiple human diseases, including
      cervical cancer caused by multiple high-risk types and genital warts caused by
      the low-risk types 6 and 11. Based on the research indicating that low-risk HPV
      could be successfully targeted by inhibitors of viral DNA replication, we carried
      out several high-throughput screens for inhibitors of DNA replication activities.
      Two series were identified in screens for inhibitors of the interaction between
      the viral proteins E1 and E2. The two series were demonstrated to bind to
      overlapping sites on the transactivation domain of E2, at the E1-binding
      interface, by a series of biochemical and biophysical experiments. A member of
      the first series was also cocrystallized with the E2 transactivation domain. For
      both series, structure-activity investigations are described, which resulted in
      several hundred fold improvements in activity. The best compounds in each series
      had low nanomolar activity against the HPV11 E1-E2 interaction, and EC(50) values
      in cellular DNA replication assays of approximately 1 MUM. Binding modes for the
      two series are compared, and some general conclusions about the discovery of
      protein-protein interaction inhibitors are drawn from the work described.

PMID- 20676972
TI  - Mutagenesis protocols in Saccharomyces cerevisiae by in vivo overlap extension.
AB  - A high recombination frequency and its ease of manipulation has made
      Saccharomyces cerevisiae a unique model eukaryotic organism to study homologous
      recombination. Indeed, the well-developed recombination machinery in S.
      cerevisiae facilitates the construction of mutant libraries for directed
      evolution experiments. In this context, in vivo overlap extension (IVOE) is a
      particularly attractive protocol that takes advantage of the eukaryotic apparatus
      to carry out combinatorial saturation mutagenesis, site-directed recombination or
      site-directed mutagenesis, avoiding ligation steps and additional PCR reactions
      that are common to standard in vitro protocols.

PMID- 20676973
TI  - In vitro mutagenesis of Brucella species.
AB  - Three major techniques have been employed for broad-range in vitro mutagenesis of
      Brucella species. Shotgun approaches capable of generating large libraries of
      randomly inserted transposon mutants include Tn5, mariner (Himar1), and mini-Tn5
      signature-tagged mutagenesis. Allelic exchange has also been extensively employed
      for targeted gene deletion. In general, plasmid and transposon delivery into
      Brucella has relied upon electroporation; however, conjugation has also been
      successfully employed. Both approaches have been used to identify critical
      virulence determinants necessary for disease and intracellular survival of the
      organism. Perhaps more importantly these approaches have provided an opportunity
      to develop attenuated vaccine candidates of improved safety and efficacy. Future
      experiments are designed to identify individual functions that govern the
      interaction between host and agent and control intracellular trafficking and
      survival. Toward this goal, this chapter describes current approaches used to
      mutagenize Brucella spp.

PMID- 20676974
TI  - Random mutagenesis strategies for Campylobacter and Helicobacter species.
AB  - Campylobacter and Helicobacter species are important pathogens in man and
      animals. The study of their virulence and physiology has been difficult due to
      the lack of tractable genetic tools, since many of the techniques established in
      Escherichia coli and related species were found to be non-functional in
      Campylobacter and Helicobacter species. The advent of functional genomics
      techniques in the last decade has been accompanied by the development of genetic
      tools, which take advantage of specific features of Campylobacter and
      Helicobacter, like natural transformation. This has allowed for the construction
      of random mutant libraries based on in vitro transposition or ligated loops
      followed by natural transformation and recombination, thus circumventing
      selection against sequences when cloning or passaging libraries through E. coli.
      Uses of the techniques have been in the study of motility, gene expression, and
      gene essentiality. In this chapter, we discuss the approaches and techniques used
      for the construction of random mutant libraries in both Campylobacter and
      Helicobacter.

PMID- 20676975
TI  - Mutagenesis of the repeat regions of herpesviruses cloned as bacterial artificial
      chromosomes.
AB  - Cloning of infectious and pathogenic herpesvirus genomes in a bacterial
      artificial chromosome (BAC) vector greatly facilitates genetic manipulation of
      their genomes. BAC-based mutagenesis strategies of viruses can advance our
      understanding of the viral gene functions and determinants of pathogenicity, and
      can ultimately help to develop molecularly defined improved vaccines against
      virus diseases. Unlike the virus stocks, where continuous passage in tissue
      culture can lead to phenotypic alterations such as loss of virulence or
      immunogenicity, viral genomes can be stably maintained with high fidelity as BAC
      clones in bacteria. Thanks to the "RecA" or the inducible phage "lambda Red"
      homologous recombination systems and a variety of positive and negative selection
      strategies, viral genomes cloned as BAC can be efficiently manipulated in E.
      coli. All the manipulations, including DNA fragment deletion or insertion, point
      mutations, or even multiple modifications in repeat regions can be carried out
      accurately in E. coli, and the mutated DNA can be used directly to reconstitute
      mutant viruses in transfected host cells. Furthermore, using self-excision
      strategies, the non-viral bacterial replicon sequence can be excised
      automatically during virus reconstitution, thus generating recombinant viruses
      virtually identical to the wild-type parent viruses. Here, we describe the
      various technologies of manipulating the infectious BAC clones of a group E
      herpesvirus as an example through a combination of different approaches.

PMID- 20676976
TI  - An efficient protocol for VZV BAC-based mutagenesis.
AB  - Varicella-zoster virus (VZV) causes both varicella (chicken pox) and herpes
      zoster (shingles). As a member of the human herpesvirus family, VZV contains a
      large 125-kb DNA genome, encoding 70 unique open reading frames (ORFs). The
      genetic study of VZV has been hindered by the large size of viral genome, and
      thus the functions of the majority of these ORFs remain unclear. Recently, an
      efficient protocol has been developed based on a luciferase-containing VZV
      bacteria artificial chromosome (BAC) system to rapidly isolate and study VZV ORF
      deletion mutants.

PMID- 20676978
TI  - Random mutagenesis by error-prone PCR.
AB  - In vitro selection coupled with directed evolution represents a powerful method
      for generating nucleic acids and proteins with desired functional properties.
      Creating high-quality libraries of random sequences is an important step in this
      process as it allows variants of individual molecules to be generated from a
      single-parent sequence. These libraries are then screened for individual
      molecules with interesting, and sometimes very rare, phenotypes. Here, we
      describe a general method to introduce random nucleotide mutations into a parent
      sequence that takes advantage of the polymerase chain reaction (PCR). This
      protocol reduces mutational bias often associated with error-prone PCR methods
      and allows the experimenter to control the degree of mutagenesis by controlling
      the number of gene-doubling events that occur in the PCR reaction. The error
      prone PCR method described here was used to optimize a de novo evolved protein
      for improved folding stability, solubility, and ligand-binding affinity.

PMID- 20676977
TI  - A method for rapid genetic integration into Plasmodium falciparum utilizing
      mycobacteriophage Bxb1 integrase.
AB  - Genetic manipulation of the human malaria parasite Plasmodium falciparum has
      presented substantial challenges for research efforts aimed at better
      understanding the complex biology of this highly virulent organism. The
      development of methods to perform gene disruption, allelic replacement or
      transgene expression has provided important insights into the function of
      parasite genes. However, genomic integration studies have been hindered by low
      transfection and recombination efficiencies, and are complicated by the
      propensity of this parasite to maintain episomal replicating plasmids. We have
      developed a fast and efficient site-specific system of integrative recombination
      into the P. falciparum genome, which is catalyzed by the mycobacteriophage Bxb1
      serine integrase. This system has the advantage of providing greater genetic and
      phenotypic homogeneity within transgenic lines as compared to earlier methods
      based on episomal replication of plasmids. Herein, we present this methodology.

PMID- 20676979
TI  - A rapid and versatile PCR-based site-directed mutagenesis protocol for generation
      of mutations along the entire length of a cloned cDNA.
AB  - Deciphering protein function is a major challenge in modern biology and continues
      to remain at the frontier of investigations into the molecular basis of cell
      behavior. With the explosion in our bioinformatics knowledge base and the now
      widespread use of associated software tools and database resources, we have an
      enormous logistic capability to identify protein domains of interest and the
      compelling desire to introduce mutations within these sequences in order to
      ultimately understand the functional aspects of a given protein and/or test its
      therapeutic applications. Faced with this ultimate task, a quick and efficient
      means to introduce desired mutations anywhere along the protein length is
      necessary as a first step. Here, HIF1alpha and HIF2alpha are used as examples to
      demonstrate the simplicity, speed, and versatility of the PCR-based mutagenesis
      method.

PMID- 20676980
TI  - Rapid sequence scanning mutagenesis using in silico oligo design and the
      Megaprimer PCR of whole plasmid method (MegaWHOP).
AB  - A wide variety of random- and site-directed mutagenesis techniques have been
      developed to investigate the structure-function relationship in proteins and
      intergenic regions like promoter sequences. Similar techniques can be employed to
      optimize protein properties like enantioselectivity, substrate specificity, and
      stability in a directed evolution approach. Due to the tremendous genetic
      diversity that is created by common random-mutagenesis methods, directed
      evolution techniques usually require the time-consuming and cumbersome screening
      of large numbers of variants. A gene-scanning saturation-mutagenesis approach
      represents one efficient way to limit the screening effort by reducing the
      created genetic diversity. In structure/function studies often a similar method,
      e.g., alanine- or arginine-scanning mutagenesis, is used to probe the role of
      specific amino acids in a protein. Here, we present a standardized mutagenesis
      strategy that can speed up the process of scanning whole proteins for
      structure/function studies and, furthermore, allows for the fast and efficient
      generation of gene-scanning saturation-mutagenesis libraries to be used in the
      directed evolution of enzyme functions and properties. The described method uses
      automated computer-assisted oligonucleotide design, and a two-step PCR
      mutagenesis protocol to amplify site-specifically mutated circular plasmids that
      can be directly transformed in Escherichia coli expression strains.

PMID- 20676981
TI  - Insertion and deletion mutagenesis by overlap extension PCR.
AB  - Mutagenesis by the overlap extension PCR has become a standard method of creating
      mutations including substitutions, insertions, and deletions. Nonetheless, the
      established overlap PCR mutagenesis is limited in many respects. In particular,
      it has been difficult to make an insertion larger than 30 nt, since all sequence
      alterations must be embedded within the primer. Here, we describe a rapid and
      efficient method for creating insertions or deletions of any length at any
      position in a DNA molecule. This method is generally applicable, and therefore
      represents a significant improvement to the now widely used overlap extension PCR
      method.

PMID- 20676982
TI  - Targeted amplification of mutant strands for efficient site-directed mutagenesis
      and mutant screening.
AB  - Site-directed mutagenesis is an invaluable tool for functional studies and
      genetic engineering. However, most current protocols require the target DNA to be
      cloned into a plasmid vector before mutagenesis can be performed, and none of
      them are effective for multiple-site mutagenesis. We now describe a method that
      allows mutagenesis on any DNA template (e.g. cDNA, genomic DNA, and plasmid DNA),
      and is highly efficient for multiple-site mutagenesis (up to 100%). The
      technology takes advantage of the requirement that, in order for DNA polymerases
      to elongate, it is crucial that the 3' sequences of the primers match the
      template perfectly. When two outer mutagenic oligonucleotides (oligos) are
      incorporated together with the desired mutagenic oligos into the newly
      synthesized mutant strand, they serve as anchors for PCR primers which have 3'
      sequences matching the mutated nucleotides, thus amplifying the mutant strand
      only. The same principle can also be used for mutant screening.

PMID- 20676983
TI  - A modified inverse PCR procedure for insertion, deletion, or replacement of a DNA
      fragment in a target sequence and its application in the ligand interaction scan
      method for generation of ligand-regulated proteins.
AB  - Functional analysis of a protein of interest, by generation of functional
      alterations in a target protein, often requires the performance of site-directed
      mutagenesis within the gene sequence. These manipulations are usually performed
      using "cut and paste" techniques, combined with PCR. Here we describe a simple
      and general procedure to specifically insert a DNA fragment into any site within
      a given DNA sequence. We demonstrate this insertional mutagenesis by describing
      the insertion of a tetracysteine (4C) hexapeptide-encoding sequence into the
      coding sequence of the antibiotic hydrolyzing enzyme TEM-1 beta-lactamase. This
      procedure could also be applied to insert different DNA sequences or to replace,
      or delete, existing fragments in a given gene. We have recently used this
      procedure to develop a general method (ligand interaction scan - LIScan) to
      generate ligand-regulated proteins.

PMID- 20676984
TI  - Amplification of orthologous genes using degenerate primers.
AB  - This chapter describes the use of degenerate primers for PCR amplification of
      orthologous DNA from related species. While several methods for designing
      degenerate primers have been described, an important consideration is to base the
      design on a short region of highly conserved amino acids. Here, we present the
      use of a degenerate primer design strategy called Consensus-degenerate hybrid
      oligonucleotide primer (CODEHOP). This strategy is very useful when there is low
      conservation in the multiple alignments of sequences across species. We
      demonstrate the use of CODEHOP to amplify the entire coding region of the
      flightin gene from multiple Drosophila species.

PMID- 20676985
TI  - Computational evaluation of protein stability change upon mutations.
AB  - When designing a mutagenesis experiment, it is often crucial to estimate the
      stability change of proteins induced by mutations (Delta DG). Despite the recent
      advances in computational methods, it is still challenging to estimate D DG
      quickly and accurately. We recently developed the Eris protocols for in silico
      evaluation of the Delta DG. Starting from the tertiary structure of the wide-type
      protein, the Eris protocols can model the structure of the mutant protein and
      estimate Delta DG using the structure models. The Eris protocols not only
      efficiently optimize the side chains conformations, taking advantage of a fast
      rotamer-based searching algorithm, but also allow protein backbone flexibility
      during the modeling. As a result, the Eris protocols effectively resolve steric
      clashes induced by certain mutations and have more accurate Delta DG predictions
      than a fixed-backbone approach. We discuss the general aspects of computational
      Delta DG estimations and discuss in detail the principles and methodologies of
      the Eris protocols.

PMID- 20676986
TI  - Approaches for using animal models to identify loci that genetically interact
      with human disease-causing point mutations.
AB  - The complexity of human illnesses often extends beyond a single mutation in one
      gene. Mutations at other loci may act synergistically to affect the penetrance
      and severity of the associated clinical manifestations. Discovering the
      additional loci that contribute to an illness is a challenging problem. Animal
      models for disease, based on engineered point mutations in a homologous gene,
      have proven invaluable to better understand the mechanism(s) which give(s) rise
      to the observed physiological effects. Importantly, these animals can also
      function as the basis for genetic modifier screens to discover other loci which
      contribute to an illness. This chapter discusses the theory, considerations, and
      methodology for performing genetic modifier screens in animal models for human
      disease.

PMID- 20676987
TI  - Using peptide loop insertion mutagenesis for the evolution of proteins.
AB  - The insertion of peptide loops into the polypeptide chain of proteins at surface
      exposed regions is an attractive avenue to modify the protein's properties or to
      evolve new functionalities. The strategy of peptide loop insertion has, for
      example, been used to create new binding sites in protein scaffolds and has led
      to the isolation of proteins with excellent binding affinities for various
      biological structures. Peptide loops have also been inserted into enzymes to
      modulate their catalytic properties. We recently used loop insertion mutagenesis
      to evolve a mutant of O(6)-alkylguanine-DNA-alkyltransferase (AGT) that reacts
      with the nonnatural substrate O(6)-propargylguanine for applications in molecular
      imaging. In this chapter, we describe in detail the protocols that we have
      applied (1) to identify sites in AGT that are permissive to loop insertion, (2)
      to manipulate DNA to create large loop insertion libraries, and (3) to identify
      mutants with desired properties. The experimental procedures are general and can
      easily be adapted for the insertion of peptide loops into other classes of
      enzymes or into any protein of interest.

PMID- 20676988
TI  - Massive Mutagenesis: high-throughput combinatorial site-directed mutagenesis.
AB  - Massive Mutagenesis is a proprietary library creation method that enables the
      fast generation of high-quality genetic libraries. Starting from a single gene on
      a plasmid and hundreds to thousands of oligonucleotides, a one-step single-strand
      circular amplification method creates random combinations of several site
      directed substitutions, insertions, or deletions. Libraries of up to a billion
      such variants have been routinely generated. Sequencing those variants
      demonstrated lower biases than alternative approaches such as error-prone PCR.
      Screening and selecting them has yielded improved biocatalysts, therapeutic
      proteins, and antibodies.

PMID- 20676989
TI  - Directed in vitro evolution of reporter genes based on semi-rational design and
      high-throughput screening.
AB  - Marker genes, such as gusA, lacZ, and gfp, have been applied comprehensively in
      biological studies. Directed in vitro evolution provides a powerful tool for
      modifying genes and for studying gene structure, expression, and function. Here,
      we describe a strategy for directed in vitro evolution of reporter genes based on
      semi-rational design and high-throughput screening. The protocol involves two
      processes of DNA shuffling and screening. The first DNA shuffling and screening
      process involves eight steps: (1) amplifying the target gene by PCR, (2) cutting
      the product into random fragments with DNase I, (3) purification of 50-100 bp
      fragments, (4) reassembly of the fragments in a primerless PCR, (5) amplification
      of the reassembled product by primer PCR, (6) cloning into expression vector, (7)
      transformation of E. coli by electroporation, and (8) screening the target
      mutants using a nitrocellulose filter. The second DNA shuffling and screening
      process also involves the same eight steps, except that degenerate
      oligonucleotide primers are based on the sequence of the selected mutant.

PMID- 20676990
TI  - Ribosome display for rapid protein evolution by consecutive rounds of mutation
      and selection.
AB  - Directed evolution experiments are performed to improve the properties of
      proteins by creating a library of mutated genes of interest and selecting those
      genes that encode proteins exhibiting desired properties. Here, we present one of
      the methods to carry out an evolutionary experiment called ribosome display.
      Ribosome display allows this process to be carried out entirely in vitro, and it
      is therefore a rapid and robust method for protein evolution.

PMID- 20676991
TI  - Fine-tuning enzyme activity through saturation mutagenesis.
AB  - Codon saturation is a powerful tool for analyzing protein structure-function
      relationships and fine-tuning enzyme activity. In this technique, one or more key
      amino acids are randomized by incorporating degenerate codon(s) into a gene of
      interest in a polymerase-mediated primer extension reaction. Traditional methods
      for codon saturation mutagenesis are labor-intensive and typically require
      multiple rounds of PCR and restriction/ligation-based cloning. In contrast, the
      QuikChange Multi Site-Directed Mutagenesis kit provides an efficient one-day
      procedure for incorporating degenerate codons into any double-stranded plasmid
      DNA template. Originally developed for introducing point mutations at multiple
      sites, the Multi kit can be readily adapted for performing site-directed
      saturation mutagenesis of one, two, or three amino acids simultaneously. When
      coupled with a suitable screening assay, this method simplifies the process of
      surveying multiple side chain replacements at key locations.

PMID- 20676992
TI  - Characterization of structural determinants of type 1 corticotropin releasing
      hormone (CRH) receptor signalling properties.
AB  - Mammalian adaptation to stressful stimuli requires activation of the type 1
      corticotropin releasing hormone (CRH) receptor (CRH-R1), a 415 amino acid protein
      that belongs to the large superfamily of 7 transmembrane domain receptors that
      relay signals across cells through activation of G-proteins. CRH-R1 expression
      and activity is regulated at the gene level by mRNA alternative splicing that
      results in a number of CRH-R1 variants. This process can generate putative CRH-R1
      receptor variants with distinct structural and signaling properties; their study
      can provide important insights about the structural determinants of CRH-R1
      functional characteristics. Using site-directed mutagenesis by overlap extension
      polymerase chain reaction (OE-PCR), we investigated the structure-function
      relationships of a CRH-R1 variant with an extended 1st intracellular loop (IC1)
      (CRH-R1beta), a sequence modification that impairs signaling activity (such as
      cAMP production and MAPK activation). We identified a penta-amino acid cassette
      within the 29-amino acid insert of CRH-R1beta rich in positive charged amino
      acids (F(170)-R(174)), as an important structural determinant for the impaired
      cAMP response.

PMID- 20676993
TI  - Site-directed mutagenesis for improving biophysical properties of VH domains.
AB  - Recombinant antibody fragments are significant therapeutic and diagnostic
      reagents. As such, their efficacy depends heavily on their affinities and
      biophysical properties. Thus, mutagenesis approaches have been extensively
      applied to recombinant antibodies to improve their affinity, stability, and
      solubility. Among the existing recombinant antibody variants, human V(H) domains
      stand out as the ones with the general need of solubility engineering at some
      point during their development; this solubility engineering step transforms V(H)s
      into nonaggregating, functional entities, rendering them useful as therapeutic
      and diagnostic reagents. Here, we present one of several approaches that have
      been employed to develop nonaggregating human V(H) domains. We apply an in vitro
      site-directed mutagenesis approach to an aggregating human V(H) domain by means
      of a splice overlap extension technique. The resultant mutant V(H)s are
      nonaggregating in contrast to the parent wild type V(H) and less prone to
      aggregation following thermal unfolding.

PMID- 20676994
TI  - Phenotype based functional gene screening using retrovirus-mediated gene trapping
      in quasi-haploid RAW 264.7 cells.
AB  - In vitro random mutagenesis, followed by phenotype screening, provides a rapid
      and convenient tool for identifying novel genes involved in the phenotype of
      interest. However, the forward mutagenic approach in mammalian somatic cells is
      seriously limited by the diploidic nature of the genome. To overcome this
      impediment, we developed a method that allows functional screening for both
      haploid insufficient and sufficient genes involved in the phenotype of interest,
      utilizing a retrovirus gene trap mutagenesis in chemical mutagen-generated quasi
      haploid cells. This method was used to identify novel host genes that are
      required for macrophage sensitivity to anthrax lethal toxin.

PMID- 20676995
TI  - Site-directed disulfide cross-linking to probe conformational changes of a
      transporter during its functional cycle: Escherichia coli AcrB multidrug exporter
      as an example.
AB  - Many proteins, especially transporters, are thought to undergo large
      conformational alterations during their functional cycle. Since X-ray
      crystallography usually gives only the most stable conformation, other methods
      are needed to probe this conformational change. Site-directed disulfide cross
      linking is often very useful for this purpose. We illustrate this by using the
      Escherichia coli AcrB, a proton-motive-force-dependent multidrug efflux
      transporter. Crystallographic studies of the asymmetric trimer of AcrB suggest
      that each protomer in the trimeric assembly goes through a cycle of
      conformational changes during drug export (functional rotation hypothesis). Site
      directed disulfide cross-linking between those residues that come close to each
      other in only one stage in the cycle inactivated the transporter, showing that
      the conformational changes indeed occurred in vivo and that they are required for
      drug transport. A dsbA strain, which has a diminished activity to form disulfide
      bonds in the periplasm, was used to verify the conclusion by showing a restored
      transport activity in this strain. Furthermore, we describe "a real-time cross
      linking experiment," in which rapidly reacting, sulfhydryl-specific cross
      linkers, methanethiosulfonates, inactivate the AcrB double-cysteine mutant
      expressed in dsbA cells instantaneously.

PMID- 20676996
TI  - Site-specific incorporation of extra components into RNA by transcription using
      unnatural base pair systems.
AB  - The expansion of the genetic alphabet, by an unnatural base pair system, provides
      a powerful tool for the site-specific incorporation of extra, functional
      components into nucleic acids by replication and transcription. We developed
      several unnatural base pairs that function in PCR and in vitro transcription.
      Among them, a hydrophobic, unnatural base pair between 7-(2-thienyl)-imidazo[4,5
      b]pyridine (denoted by Ds) and pyrrole-2-carbaldehyde (denoted by Pa) exhibits
      high fidelity in PCR and T7 transcription. Modified Pa bases linked with
      functional groups of interest can also be site-specifically incorporated into RNA
      opposite Ds in DNA templates, by T7 RNA polymerase. Here, we describe the methods
      for the site-specific biotinylation of RNA molecules by transcription using the
      Ds-Pa pair with biotinylated PaTP (Biotin-PaTP).

PMID- 20676997
TI  - Mutagen: a random mutagenesis method providing a complementary diversity
      generated by human error-prone DNA polymerases.
AB  - Random mutagenesis is one of the most effective methodologies to generate variant
      libraries for directed protein evolution. Indeed, this approach requires no
      structural or mechanistic information and can uncover unexpected beneficial
      mutations. Here, we describe a new random mutagenesis method based on the use of
      human error-prone DNA polymerases (pol beta, pol eta and pol iota). This approach
      allows the random introduction of mutations through a single replication step
      followed by a selective PCR amplification of the replicated mutated sequences.
      The libraries generated using this methodology display different mutation rates
      and complementary mutational spectra. By taking advantage of the mutation bias of
      naturally highly error-prone DNA polymerases, MutaGen thus appears as a very
      useful tool for gene and protein randomization.

PMID- 20676998
TI  - Random-scanning mutagenesis.
AB  - Oligonucleotide-mediated mutagenesis is a useful tool for engineering nucleotide
      changes at defined positions in a DNA sequence. Oligonucleotide-based approaches
      are commonly used to introduce missense mutations at individual codons in a gene
      or gene segment, thereby revealing the functional importance of specific amino
      acid residues in a protein. For mutagenesis studies involving tracts of
      polypeptide sequence, investigators typically change each successive residue to
      alanine or to a limited number of alternative amino acids. Although these
      strategies can provide useful information, it is sometimes desirable to test a
      broader spectrum of amino acid changes at the targeted positions. This article
      describes a facile, oligonucleotide-based method for generating all 19 possible
      replacements at individual amino acid sites within a protein. This technique is
      known as "random-scanning mutagenesis" and is illustrated herein using examples
      from our studies of a conserved polymerase motif in HIV-1 reverse transcriptase.

PMID- 20676999
TI  - Easy two-step method for randomizing and cloning gene fragments.
AB  - Random mutagenesis is widely used in protein engineering to improve or alter
      protein function. Creating random mutant libraries typically requires cloning of
      randomly mutagenized fragments into an expression vector, which is laborious and
      often hampered by lack of unique and convenient restriction sites. Here, we
      report an easy two-step method that produces a more balanced mutational spectrum
      and simplifies the cloning of randomly mutagenized genes or gene fragments for
      constructing high titer random mutant libraries.

PMID- 20677001
TI  - En passant mutagenesis: a two step markerless red recombination system.
AB  - Bacterial artificial chromosomes are used to maintain and modify large sequences
      of different origins in Escherichia coli. In addition to RecA-based shuttle
      mutagenesis, Red recombination is commonly used for sequence modification. Since
      foreign sequences, such as antibiotic resistance genes as well as frt- or loxP
      sites are often unwanted in mutant BAC clones, we developed a Red-based technique
      that allows for the scarless generation of point mutations, deletions, and
      insertion of smaller and larger sequences. The method employs a sequence
      duplication that is inserted into the target sequence in the first recombination
      step and the excision of the selection marker by in vivo I-SceI cleavage and the
      second Red recombination. To allow for convenient and highly efficient
      mutagenesis without the use of additional plasmids, the E. coli strain GS1783
      with a chromosomal encoded inducible Red- and I-SceI-expression was created.

PMID- 20677000
TI  - Random mutagenesis using a mutator strain.
AB  - Random mutagenesis is a useful technique to study the functions of different gene
      products. Propagation of the genes cloned in plasmids through a mutator strain,
      like Escherichia coli XL1-red, produces randomly mutagenized plasmid libraries.
      This method offers a very simple and economic way of introducing random point
      mutations throughout the gene with a fairly high mutation rate. The whole process
      involves transformation and propagation of a plasmid containing the desired gene
      into the XL-1 red strain, isolating the mutagenized plasmid library and
      transforming this library into a desired strain for screening the mutant
      phenotype.

PMID- 20677002
TI  - Metal contents of four commercial fish species of NW Mexico.
AB  - The metal contents in tissues of fish species: M. cephalus, Diapterus sp.,
      Scomberomorus sierra and Oreochromis aureus, were determined in order to evaluate
      if their consumption might become a health risk. The liver and gills of M.
      cephalus and Diapterus sp. had the highest values of Cu, Fe and Pb. In the
      muscle, there were no interspecific differences in the Cd, Cu and Pb contents
      (0.27-0.32, 0.96-1.30 and 2.12-2.80 microg/g dw, respectively). Cd and Pb may be
      of concern, since their mean contents in the edible muscle of the four species
      are higher than the limits of the European Community.

PMID- 20677003
TI  - Integration of dynamic information for visuomotor control in young adults with
      developmental coordination disorder.
AB  - We examined the hypothesis that developmental coordination disorder (DCD)
      consists of a poor integration of distal preparatory visual information with the
      visual information that arises during movement execution. We set up a steering
      task where the action goal was to steer smoothly on a virtual winding course
      under conditions that manipulated the availability and timing of visual
      information. Participants were 20 young adults who had been diagnosed with DCD in
      their childhood and 20 typically developing age-matched controls. On a simple
      tracking task, participants with DCD were slower and more variable than controls.
      The group differences dissipated, however, when the display highlighted the
      directional changes necessary within the next 500 ms. When the latter condition
      was modified to also include the full layout of the course, however, the
      performance of the DCD group once again decreased. This result could not be
      attributed to a simple distraction effect. The results suggest that distinct
      neural mechanisms are associated with the processing of fast visual information
      for online control and longer-term action preparation based on spatial layout. In
      skilled action, cerebellar and parietal areas process information effectively and
      their outputs are integrated into one smooth movement. Because the DCD group
      showed difficulties in steering when both types of information were present, it
      is likely that this integration is suboptimal.

PMID- 20677004
TI  - Biotransformation of halogenated nonylphenols with sphingobium xenophagum bayram
      and a nonylphenol-degrading soil-enrichment culture.
AB  - When discharged in chlorinated wastewater, alkylphenol ethoxylate metabolites
      (APEMs) are often discharged in halogenated form (XAPEMs, X = Cl, or Br). The
      potential environmental impact of XAPEM release was assessed by studying the
      biotransformation of halogenated nonylphenol by Sphingobium xenophagum Bayram and
      a soil-enrichment culture. S. xenophagum Bayram transformed chlorinated
      nonylphenol (ClNP) slowly and nearly completely to form nonyl alcohol; the
      monobrominated nonylphenol (BrNP) and dibrominated nonylphenol were transformed
      cometabolically with nonylphenol (NP) as the primary substrate. The presence of
      either ClNP or BrNP in the S. xenophagum Bayram cultures retarded the
      transformation of nonhalogenated NP. NP-degrading soil cultures transformed
      nonhalogenated NP to a mixture of nonyl alcohols but were not capable of
      transforming either ClNP or BrNP. The presence of either ClNP or BrNP retarded
      the transformation of nonhalogenated NP in the soil cultures, as was observed in
      S. xenophagum Bayram cultures. Predicting the environmental fate of alkylphenol
      ethoxylate residues requires considering APEM halogenation during effluent
      chlorination and inhibitory effects as well as the refractory nature of
      halogenated metabolites.

PMID- 20677005
TI  - Morphometrical analysis of the human mandibular canal: a CT investigation.
AB  - PURPOSE: This study aimed to clarify the correct localization of the mandibular
      canal (MC) that is essential in order to avoid injuries to the inferior alveolar
      neurovascular bundle during oral surgical procedures. METHODS: We have analyzed
      the position of the MC using computed tomography data bank examinations of the
      oral region from 50 partially dentulous Brazilian patients aging from 25 to 75
      years old (mean +/- SD values = 51.70 +/- 4.50; females = 27; males = 23) that
      were obtained with the purpose of dental restoration and without any gross
      pathology of the mandible. Axial images were 1-mm-thick slices using bone regular
      algorithm, without intravenous contrast. RESULTS: We have measured (mean +/- SD)
      the orthogonal distances between the MC and the following selected regions of the
      mandible: (a) the buccal cortical plate (6.10 +/- 1.52 mm); (b) the inferior
      border of the mandible (10.55 +/- 2.28 mm); (c) the lingual cortical plate (3.98
      +/- 1.14 mm); and (d) the superior border of the alveolar process (16.98 +/- 2.85
      mm). CONCLUSIONS: Our morphometric findings may help clarifying the detailed
      anatomy of the MC and its topographical relations for the planning of dental
      implantation.

PMID- 20677006
TI  - High-pitch dual-source CT angiography of the aortic valve-aortic root complex
      without ECG-synchronization.
AB  - PURPOSE: To compare image quality and radiation dose of high-pitch computed
      tomography angiography(CTA) of the aortic valve-aortic root complex with and
      without prospective ECG-gating compared to a retrospectively ECG-gated standard
      pitch acquisition. MATERIALS AND METHODS: 120 patients (mean age 68+/-13 years)
      were examined using a 128-slice dual-source CT system using prospectively ECG
      gated high-pitch (group A; n=40), non-ECG-gated high-pitch (group B; n=40) or
      retrospectively ECG-gated standard-pitch (C; n=40) acquisition techniques. Image
      quality of the aortic root, valve and ascending aorta including the coronary
      ostia was assessed by two independent readers. Image noise was measured,
      radiation dose estimates were calculated. RESULTS: Interobserver agreement was
      good(kappa=0.64-0.78). Image quality was diagnostic in 38/40 patients (group A),
      37/40(B) and 38/40(C) with no significant difference in number of patients with
      diagnostic image quality among all groups (p=0.56). Significantly more patients
      showed excellent image quality in group A compared to groups B and C (each,
      p<0.01). Average image noise was significantly different between all groups
      (p<0.05). Mean radiation dose estimates in groups A and B (each; 2.4+/-0.3 mSv)
      were significantly lower compared to group C (17.5+/-4.4 mSv; p<0.01).
      CONCLUSION: High-pitch dual-source CTA provides diagnostic image quality of the
      aortic valve-aortic root complex even without ECG-gating at 86% less radiation
      dose when compared to a standard-pitch ECG-gated acquisition.

PMID- 20677007
TI  - T1-weighted MRI for the detection of coronary artery plaque haemorrhage.
AB  - OBJECTIVE: Hyperintense areas in atherosclerotic plaques on pre-contrast T1
      weighted MRI have been shown to correlate with intraplaque haemorrhage. We
      evaluated the presence of T1 hyperintensity in coronary artery plaques in
      coronary artery disease (CAD) patients and correlated results with multi-detector
      computed tomography (MDCT) findings. METHODS: Fifteen patients with CAD were
      included. Plaques detected by MDCT were categorised based on their Hounsfield
      number. T1-weighted inversion recovery (IR) MRI prepared coronary MRI for the
      detection of plaque and steady-state free-precession coronary MR-angiography for
      anatomical correlation was performed. After registration of MDCT and MRI, regions
      of interest were defined on MDCT-visible plaques and in corresponding vessel
      segments acquired with MRI. MDCT density and MR signal measurement were performed
      in each plaque. RESULTS: Forty-three plaques were identified with MDCT. With IR
      MRI 5/43 (12%) plaques were hyperintense, 2 of which were non-calcified and 3
      mixed. Average signal-to-noise and contrast-to-noise ratios of hyperintense
      plaques were 15.7 and 9.1, compared with 5.6 and 1.2 for hypointense plaques.
      Hyperintense plaques exhibited a significantly lower CT density than hypointense
      plaques (63.6 vs. 140.8). There was no correlation of plaque signal intensity
      with degree of stenosis. CONCLUSION: T1-weighted IR-MRI may be useful for non
      invasive detection and characterisation of intraplaque haemorrhage in coronary
      artery plaques.

PMID- 20677008
TI  - Oxidative damage and plasma antioxidant capacity in relation to body size, age,
      male sexual traits and female reproductive performance in the collared flycatcher
      (Ficedula albicollis).
AB  - The study of oxidative stress is a potential tool for studying the functional
      interactions among life history traits, sexual traits and physiological status in
      animals. In this study, we investigated relationships between measures of plasma
      oxidative status and male sexual traits, female reproductive investment and three
      other life history traits, in a wild population of collared flycatchers (Ficedula
      albicollis). Flycatcher males with a larger white forehead patch had higher level
      of plasma antioxidant capacity. For females, clutch size was not associated with
      plasma oxidative status, but egg size was positively correlated with antioxidant
      capacity. The relationship between age and levels of plasma oxidative damage
      remains controversial in this species: young female flycatchers showed higher
      levels of hydroperoxides compared to antioxidants, whereas age did not predict
      oxidative status of males. Males had higher levels of oxidative damage than
      females, although the concentration of antioxidant compounds was similar between
      the sexes. Females that mated with more ornamented males had higher plasma
      antioxidant capacity. Our results suggest that, for males and females, greater
      investment in sexual signal and reproduction, respectively, does not reduce the
      capacity for self-maintenance or avoidance of oxidative stress. Finally, our data
      support indirectly the occurrence of assortative mating in our species, since
      females with higher plasma antioxidant capacity mated with more ornamented males.

PMID- 20677009
TI  - Detection of nerve fiber atrophy in apparently effectively treated papilledema in
      idiopathic intracranial hypertension.
AB  - BACKGROUND: Since papilledema in idiopathic intracranial hypertension is a
      passive event not primarily affecting the visual tract, resolution with
      restitution ad integrum is expected if intracranial pressure is rebalanced.
      Retinal nerve fiber swelling due to papilledema in the acute phase and possible
      axon loss after long-lasting elevated intracranial pressure was investigated in a
      controlled cross-sectional study by scanning laser polarimetry. METHODS: A cohort
      of 23 patients with idiopathic intracranial hypertension according to the
      modified Dandy diagnostic criteria, and 23 controls matched for age and gender
      were investigated. All patients received neurological and ophthalmologic
      examination including scanning laser polarimetry (GDx VCC). Patients were divided
      into groups depending on the presence of a papilledema (group 1) or the
      regression of the papilledema after initiation of therapy (group 2). Therapy was
      based on recommendations of the German Society of Neurology. RESULTS: Scanning
      laser polarimetry showed an increase of nerve fiber thickness in group 1, and a
      decrease of the nerve fiber thickness in group 2 compared to controls. Ten of 13
      patients showed signs of a regional axon loss in the deviation map of the GDx
      report, and six had a Nerve Fiber Index above 30. All patients with regressive
      papilledema and coincidence of visual field damage and pale optic disc appearance
      had a pathologic result in the GDx examination, but only four of ten patients
      with a pathologic GDx examination showed coincidence of pale optic disc
      appearance and visual field damage as sign of underlying optic disc atrophy.
      CONCLUSION: In patients with apparently effective treatment of clinical symptoms
      and a regression of papilledema in idiopathic intracranial hypertension, a
      retinal axon loss was detected by scanning laser polarimetry. Axon loss was even
      present in patients without clinical evidence of optic nerve atrophy.

PMID- 20677010
TI  - Beta-catenin signaling involves HGF-enhanced HepG2 scattering through activating
      MMP-7 transcription.
AB  - It is well accepted that cell scattering (dispersion of clustered cells into
      single cells) is the initial step of tumor metastasis, and the downregulation of
      E-cadherin is associated with metastatic potential of tumor cells; however, the
      molecular mechanisms underlying loss of E-cadherin during tumor development are
      still poorly understood. Here, we report that hepatocyte growth factor (HGF)
      induced E-cadherin downregulation and cell scattering are attributed to the
      activation of Wnt/beta-catenin signaling and transcriptional activation of matrix
      metalloproteinase MMP-7. Furthermore, the increased MMP-7 is secreted into the
      medium and cleaves the ectodomain of E-cadherin. Inhibition of HGF signal by
      siRNA of c-Met, blocking the beta-catenin transcriptional activity through a
      dominant negative form of TCF4, MMP-7 knockdown by siRNA or suppression of MMP-7
      enzymatic activity with a neutralization antibody allowed inhibition of HGF
      induced loss of E-cadherin and HepG2 scattering. Our data presented here revealed
      the intrinsic mechanism of HGF activated Wnt/beta-catenin signaling regulation of
      HepG2 cell scattering through MMP-7 transcription activation and E-cadherin
      degradation. The results suggest that the blocking of HGF/c-Met/beta-catenin/MMP
      7/E-cadherin signaling pathway might present a practical therapeutic target for
      interference with hepatocellular carcinoma metastasis.

PMID- 20677011
TI  - Overexpression of YAP1 induces immortalization of normal human keratinocytes by
      blocking clonal evolution.
AB  - YAP1 is a transcriptional co-activator able to bind several transcription
      factors. YAP1 was termed a candidate oncogene after it was shown to be in human
      chromosome 11q22 amplicon; besides the genomic amplification, several experiments
      indicated that it has oncogenic function. However, YAP1 was also reported to be a
      tumor suppressor as its gene locus is deleted in some breast cancers. To clarify
      the role of this protein in the physiology of rapidly renewal cells, we
      investigated YAP1 in human keratinocytes. Here, we show that YAP1 overexpression
      in primary human keratinocytes blocks clonal evolution and induces cell
      immortalization, but not malignant transformation. YAP1 overexpression led to an
      increase in cell proliferation, colony forming efficiency and holoclone
      percentage. Cells escaped from senescence, immortalized but still remained unable
      to grow in soft agar or express mesenchymal markers, suggesting that YAP1
      overexpression is not sufficient to promote a complete epithelial-mesenchymal
      transition and tumorigenic transformation. Protein analysis showed an increase in
      epithelial proliferation markers and a decrease in epithelial differentiation
      markers. The expression of LEKTI, a late differentiation marker, dramatically
      dropped to undetectable levels. Taken together, these data suggest that YAP1
      overexpressing keratinocytes are maintained in the proliferative compartment.

PMID- 20677013
TI  - Susceptibility to chronic thromboembolic pulmonary hypertension may be conferred
      by miR-759 via its targeted interaction with polymorphic fibrinogen alpha gene.
AB  - A deletion/insertion (Del/Ins) polymorphism of 28 base pairs (bp) in the 3'
      untranslated region (UTR) of fibrinogen alpha gene (FGA) was associated with
      thromboembolic diseases, but the underlying mechanisms remain unknown.
      Computational predication reveals that the 28 bp polymorphic fragment is
      complementary to the sequence of a microRNA, miR-759. In this study, we aim to
      investigate the association and implicated mechanisms between FGA polymorphisms
      and the susceptibility to chronic thromboembolic pulmonary hypertension (CTEPH).
      The Del/Ins polymorphism was analyzed in 190 patients with CTEPH and 628
      controls. The FGA 3'UTR and miR-759 interaction was investigated using luciferase
      assay and quantitative RT-PCR method. Expression of miR-759 and FGA in human
      tissues was investigated by RT-PCR. The results reveal that the allele frequency
      of Ins was significantly higher in the patients than in the controls (55.8 vs.
      47.1%, P=0.003, odds ratio=1.42, 95% confidence interval: 1.13-1.79). Both miR
      759 and FGA were expressed in human liver. Co-transfection of miR-759 decreased
      the expression and mRNA stability of reporter gene containing the FGA 3'UTR. The
      effect of miR-759 was stronger on the Ins allele than on the Del allele. These
      observations suggest that the expression of FGA was regulated by miR-759 through
      its interaction at the polymorphic 3'UTR sequence, which was associated with the
      susceptibility to CTEPH.

PMID- 20677012
TI  - Ty1 integrase overexpression leads to integration of non-Ty1 DNA fragments into
      the genome of Saccharomyces cerevisiae.
AB  - The integrase of the Saccharomyces cerevisiae retrotransposon Ty1 integrates Ty1
      cDNA into genomic DNA likely via a transesterification reaction. Little is known
      about the mechanisms ensuring that integrase does not integrate non-Ty DNA
      fragments. In an effort to elucidate the conditions under which Ty1 integrase
      accepts non-Ty DNA as substrate, PCR fragments encompassing a selectable marker
      gene were transformed into yeast strains overexpressing Ty1 integrase. These
      fragments do not exhibit similarity to Ty1 cDNA except for the presence of the
      conserved terminal dinucleotide 5'-TG-CA-3'. The frequency of fragment insertion
      events increased upon integrase overexpression. Characterization of insertion
      events by genomic sequencing revealed that most insertion events exhibited clear
      hallmarks of integrase-mediated reactions, such as 5 bp target site duplication
      and target site preferences. Alteration of the terminal dinucleotide abolished
      the suitability of the PCR fragments to serve as substrates. We hypothesize that
      substrate specificity under normal conditions is mainly due to
      compartmentalization of integrase and Ty cDNA, which meet in virus-like
      particles. In contrast, recombinant integrase, which is not confined to virus
      like particles, is able to accept non-Ty DNA, provided that it terminates in the
      proper dinucleotide sequence.

PMID- 20677015
TI  - Long-term dynamics of tropical walking sticks in response to multiple large-scale
      and intense disturbances.
AB  - Understanding the effects of disturbance and secondary succession on spatio
      temporal patterns in the abundance of species is stymied by a lack of long-term
      demographic data, especially in response to infrequent and high intensity
      disturbances, such as hurricanes. Moreover, resistance and resilience to
      hurricane-induced disturbance may be mediated by legacies of previous land use,
      although such interactive effects are poorly understood, especially in tropical
      environments. We address these central issues in disturbance ecology by analyzing
      an extensive dataset, spanning the impacts of Hurricanes Hugo and Georges, on the
      abundance of a Neotropical walking stick, Lamponius portoricensis, in tabonuco
      rainforest of Puerto Rico during the wet and dry seasons from 1991 to 2007. By
      synthesizing data from two proximate sites in tabonuco forest, we show that
      resistance to Hurricane Hugo (97% reduction in abundance) was much less than
      resistance to Hurricane Georges (21% reduction in abundance). Based on a powerful
      statistical approach (generalized linear mixed-effects models with Poisson error
      terms), we documented that the temporal trajectories of abundance during
      secondary succession (i.e., patterns of resilience) differed between hurricanes
      and among historical land use categories, but that the effects of hurricanes and
      land use histories were independent of each other. These complex results likely
      arise because of differences in the intensities of the two hurricanes with
      respect to microclimatic effects (temperature and moisture) in the forest
      understory, as well as to time-lags in the response of L. portoricensis to
      changes in the abundance and distribution of preferred food plants (Piper) in
      post-hurricane environments.

PMID- 20677014
TI  - An approach based on a genome-wide association study reveals candidate loci for
      narcolepsy.
AB  - Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness,
      cataplexy, and a pathological manifestation of rapid eye movement during sleep.
      Narcoleptic pathogenesis is triggered by both genetic and environmental factors.
      Recently, development of genome-wide association studies (GWAS) has identified
      new genetic factors, with many more susceptibility genes yet to be elucidated.
      Using a new approach that consists of a combination of GWAS and an extensive
      database search for candidate genes, we picked up 202 candidate genes and
      performed a replication study in 222 narcoleptic patients and 380 controls.
      Statistical analysis indicated that six genes, NFATC2, SCP2, CACNA1C, TCRA, POLE,
      and FAM3D, were associated with narcolepsy (P<0.001). Some of these associations
      were further supported by gene expression analyses and an association study in
      essential hypersomnia (EHS), CNS hypersonia similar to narcolepsy. This novel
      approach will be applicable to other GWAS in the search of disease-related
      susceptibility genes.

PMID- 20677016
TI  - The impacts of climate change on the wintering distribution of an endangered
      migratory bird.
AB  - There is now ample evidence of the effects of anthropogenic climate change on the
      distribution and abundance of species. The black-faced spoonbill (Platalea minor)
      is an endangered migratory species and endemic to East Asia. Using a maximum
      entropy approach, we predicted the potential wintering distribution for
      spoonbills and modeled the effects of future climate change. Elevation, human
      influence index and precipitation during the coldest quarter contributed most to
      model development. Five regions, including western Taiwan, scattered locations
      from eastern coastal to central mainland China, coastal areas surrounding the
      South China Sea, northeastern coastal areas of Vietnam and sites along the coast
      of Japan, were found to have a high probability of presence and showed good
      agreement with historical records. Assuming no limits to the spread of this
      species, the wintering range is predicted to increase somewhat under a changing
      climate. However, three currently highly suitable regions (northeastern Vietnam,
      Taiwan and coastal areas surrounding the South China Sea) may face strong
      reductions in range by 2080. We also found that the center of the predicted range
      of spoonbills will undergo a latitudinal shift northwards by as much as 240, 450,
      and 600 km by 2020, 2050 and 2080, respectively. Our findings suggest that
      species distribution modeling can inform the current and future management of the
      black-faced spoonbill throughout Asia. It is clear that a strong international
      strategy is needed to conserve spoonbill populations under a changing climate.

PMID- 20677017
TI  - Physiological and fermentation properties of Bacillus coagulans and a mutant
      lacking fermentative lactate dehydrogenase activity.
AB  - Bacillus coagulans, a sporogenic lactic acid bacterium, grows optimally at 50-55 
      degrees C and produces lactic acid as the primary fermentation product from both
      hexoses and pentoses. The amount of fungal cellulases required for simultaneous
      saccharification and fermentation (SSF) at 55  degrees C was previously reported
      to be three to four times lower than for SSF at the optimum growth temperature
      for Saccharomyces cerevisiae of 35  degrees C. An ethanologenic B. coagulans is
      expected to lower the cellulase loading and production cost of cellulosic ethanol
      due to SSF at 55  degrees C. As a first step towards developing B. coagulans as
      an ethanologenic microbial biocatalyst, activity of the primary fermentation
      enzyme L-lactate dehydrogenase was removed by mutation (strain Suy27). Strain
      Suy27 produced ethanol as the main fermentation product from glucose during
      growth at pH 7.0 (0.33 g ethanol per g glucose fermented). Pyruvate dehydrogenase
      (PDH) and alcohol dehydrogenase (ADH) acting in series contributed to about 55%
      of the ethanol produced by this mutant while pyruvate formate lyase and ADH were
      responsible for the remainder. Due to the absence of PDH activity in B. coagulans
      during fermentative growth at pH 5.0, the l-ldh mutant failed to grow
      anaerobically at pH 5.0. Strain Suy27-13, a derivative of the l-ldh mutant strain
      Suy27, that produced PDH activity during anaerobic growth at pH 5.0 grew at this
      pH and also produced ethanol as the fermentation product (0.39 g per g glucose).
      These results show that construction of an ethanologenic B. coagulans requires
      optimal expression of PDH activity in addition to the removal of the LDH activity
      to support growth and ethanol production.

PMID- 20677019
TI  - An integrated theoretical approach to substance use and risky sexual behavior
      among men who have sex with men.
AB  - Research demonstrates a consistent association between substance use and sexual
      risk, particularly among men who have sex with men (MSM). The present study
      builds upon two existing theories (Cognitive Escape Theory and Expectancy Theory)
      to examine the synergistic role of sexual conflict (surrounding unsafe sex) and
      expectancies in sexual behavior among 135 MSM. Two conflicts were examined: (1)
      The conflict between motivation to practice safer sex and temptation for
      unprotected sex; and (2) The conflict between motivation to practice safer sex
      and perceived benefits of unprotected sex. Factorial ANOVAs (2 * 2; high versus
      low expectancies and conflict versus no conflict) revealed a significant
      interaction between conflict and expectancies-individuals who reported high
      levels of conflict were more sensitive to the effect of expectancies than were
      those experiencing low levels of sexual conflict. Results demonstrate the
      synergistic effects of conflict and expectancies and highlight the importance of
      integrating existing theories to more fully consider the intrapsychic operation
      and experience of sexual conflicts.

PMID- 20677020
TI  - DNA oligonucleotides and plasmids perform equally as donors for targeted gene
      conversion.
AB  - Site-specific gene modifications in cells are initiated by the introduction of
      exogenous DNA. We used a recently established cell assay to compare the ability
      of DNA donors to induce a single point mutation that converts a target gene
      encoding blue fluorescent protein (BFP) into expressing green fluorescent protein
      (GFP). In a chromosomal assay with cells stably expressing BFP, we showed that
      fluorescently labeled single-stranded oligonucleotides and a donor plasmid
      cotranscribing a red fluorescent protein provide similar efficiencies in
      triggering BFP-GFP conversions. In transient cotransfections, an isogenic donor
      plasmid comprising a nonfunctional GFP gene yielded a greater efficiency for the
      conversion of the BFP target gene than a nonisogenic donor, and all plasmid
      donors were superior to oligonucleotides.

PMID- 20677021
TI  - Multiple roles of ATP:cob(I)alamin adenosyltransferases in the conversion of B12
      to coenzyme B12.
AB  - Our mechanistic understanding of the conversion of vitamin B(12) into coenzyme
      B(12) (a.k.a. adenosylcobalamin, AdoCbl) has been substantially advanced in
      recent years. Insights into the multiple roles played by ATP:cob(I)alamin
      adenosyltransferase (ACA) enzymes have emerged through the crystallographic,
      spectroscopic, biochemical, and mutational analyses of wild-type and variant
      proteins. ACA enzymes circumvent the thermodynamic barrier posed by the very low
      redox potential associated with the reduction of cob(II)alamin to cob(I)alamin by
      generating a unique four-coordinate cob(II)alamin intermediate that is readily
      converted to cob(I)alamin by physiological reductants. ACA enzymes not only
      synthesize AdoCbl but also they deliver it to the enzymes that use it, and in
      some cases, enzymes in which its function is needed to maintain the fidelity of
      the AdoCbl delivery process have been identified. Advances in our understanding
      of ACA enzyme function have provided valuable insights into the role of specific
      residues, and into why substitutions of these residues have profound negative
      effects on human health. From an applied science standpoint, a better
      understanding of the adenosylation reaction may lead to more efficient ways of
      synthesizing AdoCbl.

PMID- 20677022
TI  - Clinical study on detecting false non-reactive of non-stress test by improved
      acoustic stimulation.
AB  - PURPOSE: To approach the clinical significance on detecting false non-reactive of
      non-stress test (NST) by improved acoustic stimulation. METHOD: One-hundred and
      sixteen pregnant women who were at 34-41 weeks' gestation were monitored for the
      fetal movement and the fetal heart rate. Then, the improved acoustic stimulation
      which was caused by clapping hands about 1 cm above maternal abdomen over the
      fetal vertex was given to the pregnant women whose NST were non-reactive.
      RESULTS: Among the 485 NST tests, 143 were non-reactive, accounting for 29.5%.
      With improved acoustic stimulation, 132 of them turned to be reactive, accounting
      for 92.3%. With oxygen therapy, 5 of the 11 changed to be reactive, but the other
      six pregnant women were given emergency caesarean section, and three of them were
      fetal distress. Among the 110 reactive pregnant women, only two were fetal
      distress. The sensitivity, specificity, positive, and negative predictive values
      for predicting fetal distress of NST with improved acoustic stimulation were
      60.0, 97.3, 50.0, and 98.2%, respectively. CONCLUSION: NST with improved acoustic
      stimulation is a convenient, fast, safe, and effective method on detecting false
      non-reactive NST and it can increase the specificity of NST.

PMID- 20677023
TI  - Effects of lumbar lordosis and pelvic inlet orientation on the outcome of the
      transobturator tape sling operation in women.
AB  - PURPOSE: To determine the association between changes in lumbar lordosis (LL)
      and/or pelvic inlet (PI) orientation and the outcome of a transobturator tape
      (TOT) sling procedure. METHODS: The study population consisted of 70 patients who
      underwent the TOT sling procedure for stress urinary incontinence, and were
      evaluated by a stress test at the sixth month after the surgery. The women were
      defined as continent on the absence of both subjective complaint of leakage and
      objective leakage as a result of the test. Cases that failed, even though
      improvement may have been observed, were considered incontinent. With the use of
      a standardized protocol, lateral lumbosacral spine/pelvic X-rays were taken with
      the participants standing in their usual upright posture with hands kept at chest
      level. From these X-rays, the angle of LL and PI were measured. RESULTS: Of the
      70 cases, 42 were continent and 28 were incontinent according to the evaluation
      done during the sixth month after the TOT procedure. There were no significant
      differences with respect to age, body mass index, gravidity, vaginal parity,
      pelvic organ prolapse and comorbid diseases between the continent and incontinent
      groups. The mean angle of PI in the continent group (34 degrees , range 20-50)
      was significantly lower than in the incontinent group (37 degrees , range 28-60)
      (p = 0.012). There was no significant difference in the median angle of LL (32
      degrees , range 15-50 in continent group, 34.5 degrees , range 21-56 in
      incontinent group, p = 0.13) between the two groups. CONCLUSIONS: Women with
      continence after the TOT sling procedure have lower angle of PI than women with
      incontinence.

PMID- 20677024
TI  - A randomized controlled study investigating the necessity of routine cervical
      dilatation during elective cesarean section.
AB  - OBJECTIVE: To investigate if it was necessary to dilate the cervix routinely
      during elective cesarean section and to determine the effects of this traditional
      maneuver on maternal morbidity. METHODS: A total of 150 patients meeting
      eligibility criteria were enrolled in this prospective, randomized controlled
      study. Patients were allocated randomly into cervical dilatation group or non
      dilated group. In the cervical dilatation group, the surgeon performed cervical
      dilatation by inserting a double-gloved index finger into the cervical canal of
      the patients after extraction of placenta and membranes. Endometrial cavity
      thickness of the patients at postoperative 24 h, development of postoperative
      febrile-infectious morbidity and postoperative hemoglobin levels were evaluated
      and compared between the groups. RESULTS: The two groups were comparable with
      regard to demographic and clinical properties. Mean postoperative endometrial
      cavity thickness of the dilated group was significantly less than the non-dilated
      group (6.87 +/- 2.50, 9.51 +/- 3.35 respectively, p < 0.0001). The level of
      hemoglobin reduction was comparable between the groups (p = 0.37). Febrile
      morbidity was seen in one patient in the dilated group. Endometritis or wound
      infection was not encountered in either group during the puerperium. CONCLUSIONS:
      Cervical dilatation seems to be an unnecessary intervention during the cesarean
      section.

PMID- 20677026
TI  - The complete genome sequence of a virus associated with cotton blue disease,
      cotton leafroll dwarf virus, confirms that it is a new member of the genus
      Polerovirus.
AB  - Cotton blue disease is the most important virus disease of cotton in the southern
      part of America. The complete nucleotide sequence of the ssRNA genome of the
      cotton blue disease-associated virus was determined for the first time. It
      comprised 5,866 nucleotides, and the deduced genomic organization resembled that
      of members of the genus Polerovirus. Sequence homology comparison and
      phylogenetic analysis confirm that this virus (previous proposed name cotton
      leafroll dwarf virus) is a member of a new species within the genus Polerovirus.

PMID- 20677025
TI  - The effect of cigarette smoking on cell proliferation in normal uterine cervix
      epithelium.
AB  - BACKGROUND: The aim of this study was to evaluate the effect of smoking on cell
      proliferation in normal cervical epithelium. METHODS: A total of 45 women
      undergoing hysterectomies due to uterine leiomyomata were investigated. Thirty
      were nonsmokers and 15 were current smokers. A segment of tissue was taken from
      cervix after removal of the uterus, and the identification of cell proliferation
      was performed by immunohistochemical analysis employing Ki-67 staining. The
      number of positive cells colored by Ki-67 staining was finally expressed as
      number of cells per square millimeter (mm2) of epithelium. RESULTS: The
      comparison of the number of proliferating cells measured by ki-67 staining among
      smoking and nonsmoking women did not show significant difference. Among smoking
      women, there was no significant difference related to the number of cigarettes
      smoked per day or time of consumption and epithelial cell proliferation. However,
      the total amount of cigarettes smoked throughout presented significant
      association with Ki-67 staining (p < 0.001); the number of proliferating cells
      per mm2 increased proportionally to the increase in consumption of cigarettes.
      CONCLUSIONS: The results indicated that there was no significant difference
      between cell proliferation in smokers and nonsmokers; however, it was shown that
      in the smokers' group, amount of cigarettes smoked during throughout lifetime can
      increase cell proliferation in normal cervical epithelium.

PMID- 20677027
TI  - Complete nucleotide sequence of Sida golden mosaic Florida virus and phylogenetic
      relationships with other begomoviruses infecting malvaceous weeds in the
      Caribbean.
AB  - The complete genome sequence of two isolates of the bipartite begomovirus (genus
      Begomovirus, family Geminiviridae) Sida golden mosaic Florida virus (SiGMFV) is
      presented. We propose that both isolates, found infecting Malvastrum
      coromandelianum (family Malvaceae) in Cuba, belong to a new strain of SiGMFV.
      Phylogenetic analysis showed that SiGMFV DNA-A is located in a monophyletic
      cluster that includes begomoviruses infecting malvaceous weeds from the
      Caribbean.

PMID- 20677031
TI  - Professor Martin Fishbein memorial issue.

PMID- 20677029
TI  - Drug discovery in a multidimensional world: systems, patterns, and networks.
AB  - Despite great strides in revealing and understanding the physiological and
      molecular bases of cardiovascular disease, efforts to translate this
      understanding into needed therapeutic interventions continue to lag far behind
      the initial discoveries. Although pharmaceutical companies continue to increase
      investments into research and development, the number of drugs gaining federal
      approval is in decline. Many factors underlie these trends, and a vast number of
      technological and scientific innovations are being sought through efforts to
      reinvigorate drug discovery pipelines. Recent advances in molecular profiling
      technologies and development of sophisticated computational approaches for
      analyzing these data are providing new, systems-oriented approaches towards drug
      discovery. Unlike the traditional approach to drug discovery which is typified by
      a one-drug-one-target mindset, systems-oriented approaches to drug discovery
      leverage the parallelism and high-dimensionality of the molecular data to
      construct more comprehensive molecular models that aim to model broader
      bimolecular systems. These models offer a means to explore complex molecular
      states (e.g., disease) where thousands to millions of molecular entities
      comprising multiple molecular data types (e.g., proteomics and gene expression)
      can be evaluated simultaneously as components of a cohesive biomolecular system.
      In this paper, we discuss emerging approaches towards systems-oriented drug
      discovery and contrast these efforts with the traditional, unidimensional
      approach to drug discovery. We also highlight several applications of these
      system-oriented approaches across various aspects of drug discovery, including
      target discovery, drug repositioning and drug toxicity. When available, specific
      applications to cardiovascular drug discovery are highlighted and discussed.

PMID- 20677032
TI  - Demographic factors and sexist beliefs as predictors of condom use among Latinos
      in the USA.
AB  - Based on a survey conducted among 198 Latinos in Central Illinois, USA, this
      study shows that income, education, and language skills were important predictors
      of condom use. In addition, hostile and benevolent sexist ideas had a differing
      impact on condom use. Hostile sexist ideas, such as the belief that women try to
      control men, increased condom use with both main and occasional partners.
      Benevolent sexism, for example, the idea that women should be cherished and
      protected, was negatively and significantly correlated with condom use with main
      partner. In this sense, benevolent sexism, an apparently less harmful type of
      prejudice against women, seems to out them at higher risk of HIV/AIDS infection.
      Therefore, HIV/AIDS prevention interventions designed for Latinos should not only
      address the dangers of hostile sexist beliefs in reproducing negative feelings
      about women but also the problems associated with benevolent sexist beliefs,
      which seem to decrease condom use.

PMID- 20677033
TI  - Effects of oral exposure of pigs to deoxynivalenol (DON) sulfonate (DONS) as the
      non-toxic derivative of DON on tissue residues of DON and de-epoxy-DON and on
      DONS blood levels.
AB  - The Fusarium toxin deoxynivalenol (DON) is of outstanding importance in pig
      nutrition because of its frequent occurrence in cereal grains at levels high
      enough to cause adverse effects such as a decrease in feed intake and impairment
      of the immune system. Thus, simple decontamination procedures would be useful.
      The present study aimed to examine the effects of wet preservation of triticale
      contaminated with DON and zearalenone (ZON) with sodium metabisulphite (SBS) on
      the treatment-related non-toxic derivative of DON (DON-sulfonate, DONS), and on
      ZON and its metabolites in blood and various physiological specimens of piglets.
      The uncontaminated control triticale (CON) and the DON-contaminated triticale
      (FUS) were included in the diets either untreated or SBS treated (CON-SBS, FUS
      SBS) and fed to piglets for 28 days starting from weaning. The diet
      concentrations for DON were 0.156, 0.084, 2.312 and 0.275 mg kg(-1), for DONS
      were <0.05, <0.05, <0.05 and 1.841 mg kg(-1), and for ZON were <0.001, 0.006,
      0.017, and 0.016 mg kg(-1) for each of CON, CON-SBS, FUS and FUS-SBS,
      respectively. DONS was present in the blood of piglets fed the FUS-SBS at a
      median concentration of 15.5 ng ml(-1) (3-67 ng ml(-1)), while the median DON
      concentration amounted to 2 ng ml(-1) (0-5 ng ml(-1)) at the same time. The
      median DON concentration in the blood of piglets fed the FUS diet reached a
      median concentration of 10.5 ng ml(-1) (5-17 ng ml(-1)). Moreover, the relative
      differences between the DON concentrations in other physiological specimens
      (muscle, liver, kidney, bile and urine) in piglets fed the FUS-SBS and the FUS
      diet were comparable with the blood DON concentration differences. Although these
      differences can be taken as an indication for DONS stability after absorption and
      distribution further studies examining DONS in these other physiological
      specimens directly are necessary to substantiate this conclusion. Moreover, ZON
      and alpha-zearalenol could only be detected in bile and urine where their levels
      were not influenced by the SBS treatment.

PMID- 20677035
TI  - The curtain of culture. Editorial.

PMID- 20677034
TI  - Individual and collective determinants of mental health during wartime. A survey
      of displaced populations amidst the July-August 2006 war in Lebanon.
AB  - It is well known that war has negative effects on the mental health of civilian
      populations. However, different perceptions and reactions to trauma have
      different impacts on the psychological well-being of affected populations. This
      study assessed the mental health status of adult internally displaced persons
      (IDPs) at an early stage of the summer 2006 war in Lebanon, and investigated the
      relationship between their mental status and socio-demographic determinants, and
      individual and collective experiences of the war. Two hundred and eighteen IDPs
      were surveyed for the prevalence and determinants of acute trauma symptoms. The
      reporting of anxiety symptoms was assessed using a version of the Hamilton
      Anxiety Rate Scale that was translated into Arabic. The prevalence of self
      reported anxiety symptoms was relatively low, at 25.8%. After adjustment, the
      outcome variable was significantly associated with being female (OR=2.9),
      experiencing bombing while fleeing (OR=2.8) and being surveyed in days of bad
      political news (OR=2.7). Factors related to displacement circumstances and coping
      strategies showed no significance. This result suggests that individual and
      collective war experience had an equal importance in predicting anxiety. This
      study recommends the consideration of factors operating at a collective level for
      better understanding civilians' mental health in times of war.

PMID- 20677036
TI  - The sociocultural contexts of attempting suicide among women in Iran.
AB  - In this study, we investigated the sociocultural contexts of suicide attempts
      among women in Iran. Fifty women who attempted suicide and were admitted to the
      two main hospitals in Isfahan in 2006 were interviewed. The main themes
      identified were family problems, marriage and love, social stigma, pressure of
      high expectations, and poverty. We observed significant sociocultural influence
      on attempting suicide among the Iranian women in this study. Based on our
      findings we conclude that the women in the study were affected by social changes
      and the interplay between traditional and modern values and attitudes.
      Understanding sociocultural aspects of suicide in Iran is critical in providing
      effective and culturally sensitive suicide prevention and care programs.

PMID- 20677037
TI  - Cancer perceptions of South African mothers and daughters: implications for
      health promotion programs.
AB  - Cancer is one of the leading causes of death worldwide. A major reason why women
      do not obtain cancer screening procedures relates to the high levels of fear
      associated with cancer. In this study, we explored South African mothers' and
      daughters' reaction to the word "cancer" specifically. The study sample included
      157 randomly selected mother and adolescent daughter pairs from an urban
      community in Cape Town, South Africa. Mothers and their adolescent daughters had
      very similar responses to the term "cancer." We found that most South African
      mothers and daughters had a fear-based attitude toward the illness. When we asked
      mothers what they immediately thought of upon hearing "cancer," a majority of
      women (69%) thought of death, and another 43% thought of suffering and the
      detrimental consequences of the illness. Similarly, 50% of the daughters also
      thought of death, and 42% thought of the detrimental aspects of cancer.
      Fatalistic attitudes and negative emotional reactions have important implications
      in cancer prevention and need to be addressed within a public health context.

PMID- 20677038
TI  - An exploration of rural and urban Kenyan women's knowledge and attitudes
      regarding breast cancer and breast cancer early detection measures.
AB  - Many women in Kenya with breast cancer symptoms do not seek medical attention
      until their cancer is very advanced, leading to high mortality rates and a heavy
      cancer burden on the nation. In this study we employed eight focus groups with
      low- and middle-income rural and urban Kenyan women to explore their knowledge,
      attitudes, and behaviors concerning breast cancer and its early detection
      measures. Topics for discussion were derived from the components of the Health
      Belief Model (HBM). Findings revealed a huge divide between urban middle-income
      women and all other groups with respect to knowledge of breast cancer and early
      detection measures. In addition, women viewed breast cancer as a highly severe
      disease. Perceived benefits of early detection measures centered around preparing
      themselves for what was assumed to be inevitable death.

PMID- 20677039
TI  - Iranian women's perception and beliefs about breast cancer.

PMID- 20677040
TI  - Adolescent girls define menstruation: a multiethnic exploratory study.
AB  - Incomplete understanding of menstruation may place girls at risk for sexually
      transmitted diseases (STDs) and unintended pregnancy. Prior research suggests
      that European American and African American girls incompletely understand
      menstruation, yet little is known about menstrual knowledge in other ethnic
      groups. Using audiotaped focus group and individual interviews with 73 African
      American, Mexican American, Arab American, and European American girls, we
      assessed girls' menstrual understanding. Responses included reproduction, growing
      up, cleansing, messages about femininity, and not knowing. We found ethnic
      differences in the prominence of these themes. We learned that social and
      cultural factors play an important role in transmission of menstrual knowledge.

PMID- 20677041
TI  - Finding a balance: health promotion challenges of military women.
AB  - In this study, we explored what may determine, or predict, United States military
      women's health promotion behaviors. Using a descriptive correlational design
      grounded in Pender's Health Promotion model, 491 military women completed
      instruments measuring their demographic variables, perception of health,
      definition of health, self-efficacy, and interpersonal influences to determine
      the significant factors affecting participation in health promotion activities.
      The outcome indicated that self-efficacy and interpersonal influences were the
      most influential in determining health promotion. This research illuminates some
      of the challenges working women face in meeting health promotion activities and
      how best to support their ability to participate in healthy behaviors.

PMID- 20677043
TI  - A study of quantitative content analysis of health messages in U.S. media from
      1985 to 2005.
AB  - Content analysis is a research method that was traditionally utilized by
      communication scholars, but as the study of media messages has grown, scholars in
      other fields have increasingly relied on the methodology. This paper reports on a
      systematic review of studies using quantitative content analysis methods to
      examine health messages in the mass media, excluding the Internet, from 1985 to
      2005. We searched for health-related content analysis studies published in peer
      reviewed journals, identifying 441 articles meeting inclusion criteria. We
      examined article attributes including theories used, topics, media type, and
      intercoder reliability measures, and looked at differences over time. Our
      findings show that studies focusing on health-related messages increased from
      1985 to 2005. During this time, studies primarily examined magazines, television,
      and newspapers, with an emphasis on topics related to substance use, violence,
      sex, and obesity and body image. Results suggest that studies published in
      communication journals are significantly more likely to include intercoder
      reliability data and theory discussion. We recommend that all publications,
      regardless of discipline or impact factor, request the inclusion of intercoder
      reliability data reported for individual variables, and suggest that authors
      address theoretical concepts when appropriate. We also encourage authors to
      include the term "content analysis," as well as media type and health topic
      studied, as keywords to make it easier to locate articles of interest when
      conducting literature searches.

PMID- 20677044
TI  - Relevance of health warnings on cigarette packs: a psycholinguistic
      investigation.
AB  - Although most research on the effect of tobacco warnings has been focused on
      attitude changes following the presentation of tobacco warnings, this paper takes
      a somewhat new perspective by investigating cognitive processing of tobacco
      warnings by adolescents of different ages (i.e., 14-, 16-, and 18-year-olds).
      More specifically, this paper investigates the way adolescents encode different
      textual elements presented in tobacco warnings. By means of a standard
      psycholinguist paradigm (i.e., sentence evaluation paradigm), we evaluated
      tobacco warnings differing along three variables: (1) severity, (2) time
      consequence and (3) target (health vs. others). Our main result demonstrated
      noticeable differences between the age groups and between smoking experiences in
      the cognitive processing of tobacco warnings. Our experimental paradigm
      represents an important step in identifying the mechanisms through which certain
      types of written warnings are cognitively processed, which in turn may well set a
      critical base for understanding decision makers' responses to risky behaviors
      such as smoking and for constructing adequate health warnings.

PMID- 20677045
TI  - Label management: investigating how confidants encourage the use of communication
      strategies to avoid stigmatization.
AB  - In modified labeling theory, Link and colleagues (1987, 1989) explicate how
      people use communication to cope with being labeled as members of a stigmatized
      group. In this paper, we change perspectives and investigate how a confidant's
      awareness of discrimination and devaluation associated with being labeled as a
      member of a stigmatized group ("mentally ill" or "smoker") motivates him or her
      to encourage a labeled loved one to engage in secrecy, withdrawal, or education
      to avoid the adverse actions associated with stigmatization. Results showed that
      a model of relationships among perceived devaluation and discrimination, coping
      strategies, and future disclosures extended well to unexpected confidants of a
      labeled loved one. This advice included encouraging the labeled loved one not to
      tell different people about their condition, which included health care
      providers. These findings also showed that people with experience in the labeling
      condition may have particular concern about stigmatization or rejection from
      different types of listeners, including close friends and health care providers.

PMID- 20677046
TI  - Motivation for health information seeking and processing about clinical trial
      enrollment.
AB  - Low patient accrual in clinical trials poses serious concerns for the advancement
      of medical science in the United States. Past research has identified health
      communication as a crucial step in overcoming barriers to enrollment. However,
      few communication scholars have studied this problem from a sociopsychological
      perspective to understand what motivates people to look for or pay attention to
      information about clinical trial enrollment. This study applies the model of Risk
      Information Seeking and Processing (RISP) to this context of health decision
      making. By recognizing the uncertainties embedded in clinical trials, we view
      clinical trial enrollment as a case study of risk. With data from a random-digit
      dial telephone survey of 500 adults living in the United States, we used
      structural equation modeling to test the central part of the RISP model. In
      particular, we examined the role of optimistic feelings, as a type of positive
      affect, in motivating information seeking and processing. Our results indicated
      that rather than exerting an indirect influence on information seeking through
      motivating a psychological need for more information, optimistic feelings have
      more direct relationships with information seeking and processing. Similarly,
      informational subjective norms also exhibit a more direct relationship with
      information seeking and processing. These results suggest merit in applying the
      RISP model to study health decision making related to clinical trial enrollment.
      Our findings also render practical implications on how to improve communication
      about clinical trial enrollment.

PMID- 20677047
TI  - Storying the temporal nature of emotion work among volunteers: bearing witness to
      the lived traumas of others.
AB  - Through an ethnographic field study of the River Valley, a rural rape crisis
      center, we explored how volunteers experienced and expressed emotion as it
      relates to temporality in the volunteering process. We sought to map the
      relatively unexplored terrain of emotion work among volunteers and disrupt
      dominant disciplinary and lay notions of what counts as "real work." Narrative
      theory offered a lens through which to observe the interconnected nature of
      volunteers' stories, organizational and societal scripts, traumatic events, and
      conceptual narratives of emotion work developed by scholars. A narrative
      perspective, with its emphasis on how characters reckon with others across time
      and space, revealed the varied temporal nature (a priori, during, post hoc) of
      emotion work for volunteers. For River Valley volunteers, their status as unpaid
      workers shaped the nature of their emotion work prior to, during, and after
      calls.

PMID- 20677048
TI  - Bearing witness to the ethics of practice: storying physicians' medical mistake
      narratives.
AB  - Medical mistakes are often referred to as the "hidden epidemic" of health because
      doctors, patients, and hospital administrators remain silent about mistakes. This
      study relies on in-depth interviews to explore how physicians story their medical
      mistake experiences. Narrative theory is used to understand how these physicians
      story the complexity of medical mistakes, highlighting how these physicians bear
      witness to medical mistakes by sharing and listening to medical mistake
      narratives. Moreover, this study showcases the implications of how practitioners
      and scholars bear witness to the oft-times emotional telling and retelling of
      health narratives.

PMID- 20677049
TI  - The influence of liking for antismoking PSAs on adolescents' smoking-related
      behavioral intentions.
AB  - In this research, we examine the influence of liking for antismoking public
      service announcements (PSAs), relative to that of PSAs' perceived argument
      strength, on adolescents' smoking-related behavioral intentions. Data from the
      first Legacy Media Tracking Survey (LMTS-I) suggest that the relative persuasive
      impact of PSA liking and perceived argument strength varies as a function of
      message recipients' smoking status. PSA liking appears to be an important
      predictor of smoking intentions for never smokers, whereas perceived argument
      strength strongly predicts quitting intentions for current smokers. For former
      smokers, both perceived argument strength and PSA liking have significant effects
      on smoking intentions, with perceived argument strength exerting a stronger
      impact. Theoretical and practical implications of the findings are discussed.

PMID- 20677050
TI  - The challenges of seeking and receiving support for women living with HIV.
AB  - Human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS)
      continue to affect a growing number of women. Because social support is essential
      to both physical and mental health, this study was designed to explore the social
      support challenges of women living with HIV. Using a grounded theory approach, 45
      women were interviewed. In their support experiences, these women encountered
      numerous challenges in seeking and receiving social support. Challenges seeking
      support included stigma and a lack of resources. Challenges receiving support
      included a mismatch of goals, concern for the providers, a lack of independence,
      and the readiness to accept the support offered. Issues concerning how these
      specific challenges factor into disclosure, the communication of support, and
      community are considered in the discussion. Future interventions and the
      development of support programs guided by this study will have the potential to
      improve the physical and psychological health of women living with HIV.

PMID- 20677051
TI  - The reluctant consumption of evidence-based decision making.

PMID- 20677052
TI  - Chronic disease: a risk we need to score.

PMID- 20677053
TI  - A profile of Australian adults who have discussed their posthumous organ donation
      wishes with family members.
AB  - Next of kin who are aware of the deceased's organ donation wishes usually will
      honor those wishes, while next of kin who are unaware of these wishes typically
      withhold consent for posthumous donation. Encouraging individuals to communicate
      or register their organ donation wishes is therefore important. Using a sample of
      409 participants, the current study sought to develop a profile of Australian
      adults who had communicated their organ donation wishes to family members.
      Christian participants and those who had a higher income were more likely to have
      communicated their donation wishes. Conversely, participants were less likely to
      have communicated their donation wishes if they were unregistered and
      undecided/opposed to organ donation, unregistered but willing to donate, or
      fearful of death. Finally, whether participants had communicated, registered, or
      communicated and registered their donation wishes was associated with their age,
      religion, attitude toward organ donation, and recall of media content about organ
      donation. Messages encouraging the communication of organ donation wishes to
      family members should therefore be targeted toward those individuals who are most
      likely to be receptive toward enacting this behavior.

PMID- 20677055
TI  - Developing culturally relevant educational materials about emergency
      contraception.
AB  - New York City has growing numbers of Mexican and Caribbean born residents, who
      have been identified as underserved communities for reproductive health care. We
      conducted exploratory focus groups to develop and test messages about emergency
      contraception that would be culturally relevant to these communities. Findings
      reveal lack of knowledge about what emergency contraception is and how it works,
      concerns about safety, and health care barriers. Multiple messages were tested in
      Spanish and English, and participants expressed positive attitudes about using
      emergency contraception once they knew that is was different from an abortion
      pill.

PMID- 20677054
TI  - The effect of format on parents' understanding of the risks and benefits of
      clinical research: a comparison between text, tables, and graphics.
AB  - There is a paucity of information regarding the optimal method of presenting
      risk/benefit information to parents of pediatric research subjects. This study,
      therefore, was designed to examine the effect of different message formats on
      parents' understanding of research risks and benefits. An Internet-administered
      survey was completed by 4,685 parents who were randomized to receive risk/benefit
      information about a study of pediatric postoperative pain control presented in
      different message formats (text, tables, and pictographs). Survey questions
      assessed participants' gist and verbatim understanding of the information and
      their perceptions of the risks and benefits. Pictographs were associated with
      significantly (p < .05) greater likelihood of adequate gist and verbatim
      understanding compared with text and tables regardless of the participants'
      numeracy. Parents who received the information in pictograph format perceived the
      risks to be lower and the benefits to be higher compared with the other formats
      (p < .001). Furthermore, compared with text and tables, pictographs were
      perceived as more "effective," "helpful," and "trustworthy" in presenting
      risk/benefit information. These results underscore the difficulties associated
      with presenting risk/benefit information for clinical research but suggest a
      simple method for enhancing parents' informed understanding of the relevant
      statistics.

PMID- 20677056
TI  - Online resources for persons recently diagnosed with HIV/AIDS: an analysis of HIV
      related webpages.
AB  - The Internet is a major source of HIV-related information and resources for
      persons recently diagnosed with HIV/AIDS (PRDHA). This study examined the types
      of HIV-related websites that appear as a result of HIV-related keyword searches
      and the extent to which website information targets PRDHA. The first page of HIV
      related webpages from 18 keyword searches was coded. Among 137 webpages meeting
      inclusion criteria, 63% represented HIV-informational websites, 31% targeted HIV
      positive individuals, and over half contained or provided access to HIV
      prevention, treatment, and transmission information. Thirty-three percent of
      webpages contained or provided access to PRDHA-targeted information, with a
      greater percentage of those webpages having mobile, non-English, and "Ask the
      Expert" features compared with non-PRDHA targeted webpages. Implications for
      PRDHA include the following: (1) they should explore HIV-related websites to gain
      insight into the credibility of the information contained on those sites; (2)
      PRDHA must be aware that HIV-related websites have the potential to elicit dated,
      emotionally distressing, or irrelevant information; and (3) to obtain information
      that relates to their demographic and situational profile, they may wish to use
      specific key terms (e.g., "HIV women") rather than attempting to navigate
      webpages that arise from general search terms (e.g., "HIV"). Recommendations for
      future development of online resources for PRDHA include providing HIV-relevant
      information in a stepwise fashion, providing demographically targeted HIV
      information, and greater utilization of mobile technology.

PMID- 20677057
TI  - A new audience segmentation tool for African Americans: the black identity
      classification scale.
AB  - Many health communications target African Americans in an attempt to remediate
      race-based health disparities. Such materials often assume that African Americans
      are culturally homogeneous; however, research indicates that African Americans
      are heterogeneous in their attitudes, behaviors, and beliefs. The Black Identity
      Classification Scale (BICS) was designed as a telephone-administered tool to
      segment African American audiences into 16 ethnic identity types. The BICS was
      pretested using focus groups, telephone pretests, and a pilot study (n = 306).
      The final scale then was administered to 625 Black adults participating in a
      dietary intervention study, where it generally demonstrated good internal
      consistency reliability. The construct validity of the BICS also was explored by
      comparing participants' responses to culturally associated survey items. The
      distribution of the 16 BICS identity types in the intervention study is
      presented, as well as select characteristics for participants with core identity
      components. Although additional research is warranted, these findings suggest
      that the BICS has good psychometric properties and may be an effective tool for
      identifying African American audience segments.

PMID- 20677058
TI  - The depiction of illness and related matters in two top-ranked primetime network
      medical dramas in the United States: a content analysis.
AB  - The effectiveness of entertainment-education is evidenced in previous research;
      nevertheless, content analytic research on the health content in such programs
      has been relatively meager in comparison to the large amount of content analyses
      of health content in news or ads in print media or on television. To address this
      issue, the current study content analyzed the portrayals of illnesses and related
      matters in 127 episodes aired from 2000 to 2007 of two top-ranked television
      medical dramas in the United States (Grey's Anatomy and ER). Results indicated
      that the two shows portrayed a wide range of illnesses and diseases, with injury,
      cardiovascular disease, and cancer being the top three most frequently portrayed.
      Moreover, equal numbers of men and women patient characters were portrayed,
      Caucasians and African Americans were the top two portrayed races, and the
      elderly were underrepresented. Last, the shows framed illness and health mainly
      from a medical perspective in references to the illness's causes, diagnosis,
      treatment, and prevention. Theoretical and practical implications are discussed.

PMID- 20677061
TI  - Collaborating and delivering literature search results to clinical teams using
      web 2.0 tools.
AB  - This article describes the experiences of librarians at the Research Medical
      Library embedded within clinical teams at The University of Texas MD Anderson
      Cancer Center and their efforts to enhance communication within their teams using
      Web 2.0 tools. Pros and cons of EndNote Web, Delicious, Connotea, PBWorks, and
      SharePoint are discussed.

PMID- 20677062
TI  - Refocusing reference services outside the library building: one library's
      experience.
AB  - In response to changing user needs, the library sought ways to meet new
      challenges and engage users outside of the building. Librarians were removed from
      the service desk in order to offer support at locations around campus. The
      service desk in the library was staffed primarily by paraprofessionals with
      librarians providing support as needed. Targeted staff training was offered, and
      different scheduling models were used over a period of time. Restructuring the
      service desk was a complicated endeavor but provided a number of benefits
      including expansion of services. Along the way, challenges were met and
      recognized as learning opportunities.

PMID- 20677064
TI  - Blogging in support of health information outreach.
AB  - Social media technologies are transforming the way librarians are collaborating,
      creating, and disseminating information. This article discusses how librarians at
      the University of Texas Health Science Center at San Antonio created a blog to
      support their health information outreach activities. Launched in 2007, the
      Staying Well Connected blog was established with the goal of promoting access to
      biomedical and health information for consumers and health professionals in the
      South Texas region. Postings highlight relevant health news, conferences, funding
      opportunities, and outreach events.

PMID- 20677063
TI  - Ten steps to increase library impact on an academic health sciences campus.
AB  - In summer 2009, the Norris Medical Library decided to increase outreach efforts
      in an attempt to revitalize its role in the USC School of Pharmacy for the
      upcoming academic year. Active networking in the summer and early fall resulted
      in an increase in use of both educational and reference services by pharmacy
      students and faculty; the number of planned instruction sessions for the 2009
      2010 academic year increased fivefold. This article identifies ten steps that
      allowed the Library to expand its role considerably in just a few months. If
      followed wholly, or in part, these ten steps will help any library become more
      involved on a health sciences campus.

PMID- 20677065
TI  - Evaluation of a library outreach program to research labs.
AB  - The goal of this study was to conduct an outcomes-based evaluation of the
      National Cancer Institute-Frederick (NCI-F) Scientific Library's Laptop Librarian
      service, where librarians took a laptop and spent time in research buildings. The
      authors used statistics from the Laptop Librarian sessions, a NCI-F community
      wide online survey, and in-person interviews to evaluate the service. The Laptop
      Librarian service increased the accessibility of librarians and saved patrons'
      time. Users gained useful information and expressed overall satisfaction with the
      service. The Laptop Librarian service proves to be a useful means for increasing
      access to librarians and providing users with necessary information at this
      government research facility.

PMID- 20677066
TI  - AbleData: a resource of assistive technology information.
AB  - The AbleData Web site provides links to a variety of resources within the broader
      category of assistive technology and rehabilitation. It contains a library of
      links to its own publications as well as related news. It also has a searchable
      database of publications on assistive technology. The site contains links to
      information centers, conferences, and other resources on these topics. Finally,
      it contains a database of 35,000 assistive technology devices and products. This
      column will focus on an overall description of what users will find at this site
      and hints for successful searching within the databases it contains.

PMID- 20677067
TI  - Firefox add-ons for medical reference.
AB  - Firefox is a Web browser created by the Mozilla project, an open-source software
      group. Features of the browser include automated updates, advanced security and
      standards compliance, and the ability to add functionality through add-ons and
      extensions. First introduced in 2004, Firefox now accounts for roughly 30% of the
      browser market. This article will focus primarily on add-ons and extensions
      available for the browser that are useful to medical researchers.

PMID- 20677068
TI  - Got value? Journal collection analysis is worth the effort.
AB  - This article presents a case study of the efforts of librarians at a pediatric
      hospital system to cut journal costs while increasing value for patrons. First,
      the worth of the libraries was proven to system leaders using a cost-benefit
      analysis. Then, librarians used a survey of library users and analysis of usage
      patterns to reevaluate the number and format of individual journal subscriptions.
      The results included cutting substantial costs and unpopular resources, adding
      more relevant resources, and garnering the respect and support of hospital
      leaders.

PMID- 20677069
TI  - COIL on wheels: a library professional development roadshow.
AB  - Professional development for instruction librarians is in danger of coming to a
      standstill in difficult economic times. COIL on Wheels is a professional
      development roadshow developed by the Community of Oklahoma Instruction
      Librarians to allow librarians with budget and staffing issues to benefit from
      peer training. By matching member librarian interests with institutional needs,
      librarians can visit institutions in their geographic area to provide their
      colleagues with low-cost or free training. This article discusses the origins of
      and rationale for this program and describes a successful implementation of this
      traveling professional development project.

PMID- 20677075
TI  - Recognition memory for 2,578 monosyllabic words.
AB  - In two studies, participants studied 30 lists of 50 words and were tested on 30
      lists of 100 words. Item-level multiple regression analyses were conducted on
      hits, false alarms, hits minus false alarms, d', and C. The predictor variables
      were objective frequency, subjective frequency, imageability, orthographic
      similarity, phonological similarity, phonological-to-orthographic N (PON), age of
      acquisition (AoA), and word length. The regression equations accounted for 45.9%
      of the variance in hit rates, 14.9% of the variance in false alarm rates, and
      29.2% of the variance in hits minus false alarms. Other noteworthy results were
      that: (a) hit rates positively correlated with false alarms, (b) objective
      frequency negatively correlated with both hit rates and false alarm rates, (c)
      AoA positively correlated with hit rates and negatively correlated with false
      alarm rates, (d) length negatively correlated with hit rates and positively
      correlated with false alarm rates, (e) orthographic uniqueness was positively
      correlated with hit rates and negatively correlated with false alarms, (f) PON
      positively correlated with false alarm rates, (g) imageability produced the
      typical mirror pattern, and (h) imageability and length were the strongest
      predictors of performance. Results were largely compatible with predictions made
      by single- and dual-process theories of recognition memory.

PMID- 20677076
TI  - The effectiveness of a group cognitive-behavioural breathlessness intervention on
      health status, mood and hospital admissions in elderly patients with chronic
      obstructive pulmonary disease.
AB  - Non-pharmacological breathlessness interventions in lung cancer have proven
      beneficial. Breathlessness is also a major symptom in chronic obstructive
      pulmonary disease (COPD). This study measured the effectiveness of a non-exercise
      based four-week cognitive-behavioural breathlessness intervention, delivered in a
      group setting for elderly patients with severe COPD. The results of the one-year
      feasibility study are presented. Patients with COPD were asked to complete the
      St. George's Respiratory Questionnaire and Hospital Anxiety and Depression Scale
      six weeks before the intervention, at the start and end of the intervention and
      at six weeks follow-up. The multidisciplinary intervention used a cognitive
      behavioural format to address understanding of COPD and medication, anxiety,
      panic and depression, activity pacing, relaxation, breathing retraining and goal
      setting. Retrospective data on accident & emergency (A&E) attendances and length
      of hospital stay was collected six months before and six months after the
      intervention and the data compared to a matched waiting list control group. The
      results showed significant improvements in depression and health status. There
      was a non-significant improvement in anxiety. There was a significant reduction
      in A&E attendance and a non-significant reduction in length of hospital stay in
      the intervention group, compared to comparative increases in the control group,
      highlighting the cost-effectiveness of the intervention.

PMID- 20677077
TI  - Lay responses to health messages about the genetic risk factors for salt
      sensitivity: do mass media genetic health messages result in genetic determinism?
AB  - Media coverage of genetics may lead to overestimation of the impact of genetics
      on disease development. In this study, we presented one student sample and one
      general public sample from the Netherlands with a general or a genetic health
      message (HM) about salt sensitivity. After reading the genetic (but not the
      general) HM, participants reported higher perceived impact of genetic versus
      lifestyle factors and a higher attributable fraction of genetics on disease
      development. Nevertheless, participants were able to recognise the balance
      between lifestyle and genetic risk factors in disease development. They also
      contextualised and restricted the message's implications to the specific
      information provided, and did not extrapolate these implications to other
      diseases. These results illustrate the nuanced understanding the general public
      may have concerning genetic risk factors.

PMID- 20677078
TI  - Crohn's disease and fatigue: constancy and co-variations of activity of the
      disease, depression, anxiety and subjective quality of life.
AB  - Fatigue in Crohn's disease (CD) is considered as a consequence of the disease and
      its treatment. If research showed the impact of the activity of the disease on
      vitality, patients can express fatigue even if the disease is inactive. Sleep
      disturbances are now considered in inflammatory bowel disease (IBD) and they
      could be involved in fatigue. It is well-known that depression and anxiety occur
      in IBD: They involve sleep disturbances and asthenia. But neither factors have
      been assessed simultaneously from a longitudinal perspective. Fifty-two patients
      participated in this study. Fatigue (MFI), depression (HAD-D), anxiety (HAD-A),
      sleep disturbances (ISI, IQPS), subjective quality of life (Mos-SF36) and
      activity of the disease (CDAI) were assessed twice with a one-year interval.
      Results showed constancy in fatigue and the mental health state. Moreover, if
      depression, anxiety, quality of life, and fatigue followed the same course of
      activity of the disease only during one visit, CDAI did not correlate with these
      dimensions between visits. CDAI only prognosticated insomnia. These results
      suggest that fatigue and poor quality of life may be primarily linked to
      depression in a secondary context of CD.

PMID- 20677079
TI  - Examining the effect of spinal cord injury on emotional awareness, expressivity
      and memory for emotional material.
AB  - The prevailing view on the effects of spinal cord injury (SCI) on emotion is that
      it dampens emotional experience due to a loss of peripheral bodily feedback, with
      the higher the lesion on the spinal cord the greater the reduction in the
      intensity of emotional experience. This view persists despite many studies
      showing an absence of such an emotional impairment in people with SCI. This study
      specifically aimed to investigate whether total cervical-6 spinal cord
      transection (i) reduces emotional expressivity and emotional awareness (ii)
      impairs memory for emotional material. The study contained three groups: 24
      patients with SCI, 20 orthopaedic injury control (OIC) patients and 20 young
      adult controls. A mixed factor design was employed to examine between group and
      within subject differences. Participants completed the Levels of Emotional
      Awareness Scale (LEAS), the Berkeley Expressivity Questionnaire (BEQ), and viewed
      an emotionally arousing slide presentation. Thirty minutes post viewing,
      participants completed memory tests for the presentation. SCI patients reported
      greater present levels of emotional expressivity compared with perceived levels
      prior to their injuries. SCI and OIC groups did not differ on any of the
      emotional awareness variables. There was also no evidence that SCI leads to
      impairment in memory for emotional events. This study's findings contradict the
      mainstream view in the cognitive neuroscience of emotion that SCI dampens
      emotional experience.

PMID- 20677080
TI  - Psychometric properties of the World Health Organization Quality of Life
      Questionnaire (WHOQOL-100) in Portuguese patients with sarcoma.
AB  - The purpose of this article is to report on the study of the psychometric
      properties of the European Portuguese version of the World Health Organization
      Quality of Life Questionnaire--WHOQOL-100, in a clinical sample of patients with
      bone and soft tissue cancer. Eighty-one participants, in different phases of the
      disease, were recruited from the Department of Orthopaedics of the Coimbra
      University Hospitals. After the informed consent was obtained, all patients
      responded to the European Portuguese version of WHOQOL-100 and the Portuguese
      versions of Beck Depression Inventory (BDI) and Brief Symptoms Inventory (BSI).
      The results show an acceptable internal consistency for the set of facets,
      domains, and 100 questions (alphas from 0.73 to 0.96) and across domains (alphas
      from 0.82 to 0.94), as well as an acceptable test-retest reliability (test-retest
      correlations from 0.71 to 0.88) of WHOQOL-100. Construct validity was
      demonstrated by moderate correlations between domains (r from 0.23 to 0.70) and
      with the general facet (r from 0.32 to 0.57), concurrent validity by its
      correlation with the total scores of BDI and Global Severity Index of BSI, and
      discriminant validity by its ability to discriminate between healthy individuals
      and cancer patients. In general, the European Portuguese version of WHOQOL-100 is
      a reliable and valid instrument for the assessment of quality of life in patients
      with bone and soft tissue cancer.

PMID- 20677081
TI  - Seasonal variation in self-reported arousal and subjective health complaints.
AB  - Many aspects of human physiology and behavior are seasonally related. Although
      there are many studies using self-ratings of, for example, subjective health and
      stress, few involve adjusting effects for seasonal differences. To estimate the
      need of adjusting for season in field studies, 24 healthy men and women were
      studied in a design that required them to fill in questionnaires on one workday
      every month, for 12 consecutive months. The results showed that ratings of stress
      were higher during winter and early spring, but only in the early afternoon and
      not in the morning or the evening. While some subjective health complaints were
      rated higher during winter, the ratings of energy and self-rated health did not
      vary throughout seasons. This concludes that seasonal variations may be a source
      of bias in questionnaire studies. Yet, further studies are needed to more
      definitely sort out which phenomena and self-rating measures that co-vary with
      season.

PMID- 20677082
TI  - Do ratings of African-American cultural competency reflect characteristics of
      providers or perceivers? Initial demonstration of a generalizability theory
      approach.
AB  - Provider cultural competency is often identified as an important component of
      effective ethnic minority healthcare. However, there is limited knowledge of the
      manner in which cultural competency judgments operate. This study sought to
      provide an initial demonstration of a hitherto overlooked methodology for
      examining the extent to which provider cultural competency ratings reflect
      characteristics of providers, differences among perceivers, and also
      idiosyncratic pairings of specific perceivers and providers. Second and third
      year medical residents rated four attending physicians for cultural competency
      when treating African-American patients. Using a Generalizability Theory
      approach, cultural competency ratings were shown to most substantially reflect
      unique perceiver and provider pairings (47.0% relationship effect). However,
      cultural competency also strongly reflected differences among resident raters in
      their tendency to perceive attending physicians as culturally competent,
      regardless of the characteristics of physicians (35.0% perceiver effect).
      Although cultural competency significantly reflected the characteristics of
      providers this effect was small (3.0% provider effect). This study demonstrates
      an overlooked methodological approach and suggests important new directions for
      conceptualizing theory and research.

PMID- 20677083
TI  - Sex and the skin: a qualitative study of patients with acne, psoriasis and atopic
      eczema.
AB  - Quantitative questionnaire-based research has suggested a considerable effect of
      skin disease on the sexual life of sufferers. In this study, we explored the
      effects of acne, psoriasis and atopic eczema upon sexual functioning and sexual
      relationships in the context of a wider exploration of the psychological sequelae
      of these diseases. We employed a qualitative methodology employing in-depth semi
      structured interviews and involving thematic analysis and constant comparison.
      Participants were patients with currently active acne, psoriasis or atopic
      eczema. Purposive sampling aimed to obtain a sample reflecting a wide range of
      participant characteristics including skin disease severity, age, sex, and care
      by general practitioner or dermatologist. Sixty-two semi-structured interviews
      were conducted. Acne had adverse effects on participants' self-perceived sexual
      attractiveness and self-confidence, as did psoriasis and eczema. But psoriasis
      and eczema also had marked effects on sexual well-being and on capacity for
      intimacy. These were related to issues of self-esteem and sexual self-image and
      were often pervasive, resulting in marked behavioural avoidance of intimate
      situations and continuing effects on sexual well-being even in long-established
      sexual relationships. Effects of psoriasis and eczema on sexual well-being and
      sexual relationships were mediated more by appearance and texture of non-genital
      skin than by involvement of genital skin. We conclude that, while recognising the
      distressing effects of acne on self-perceived sexual attractiveness, clinicians
      should be especially aware of the capacity of psoriasis and eczema to profoundly
      affect patients' psychological and sexual well-being.

PMID- 20677084
TI  - Boredom-proneness, loneliness, social engagement and depression and their
      association with cognitive function in older people: a population study.
AB  - In this study, we use data from a population survey of persons aged 65 and over
      living in the Irish Republic to examine the relationship of cognitive impairment,
      assessed using the Abbreviated Mental Test, with loneliness, boredom-proneness,
      social relations, and depression. Participants were randomly selected community
      dwelling Irish people aged 65+ years. An Abbreviated Mental Test score of 8 or 9
      out of 10 was classified as 'low normal', and a score of less than 8 as 'possible
      cognitive impairment'. We used clustering around latent variables analysis (CLV)
      to identify families of variables associated with reduced cognitive function. The
      overall prevalence of possible cognitive impairment was 14.7% (95% CI 12.4
      17.3%). Low normal scores had a prevalence of 30.5% (95% CI 27.2-33.7%). CLV
      analysis identified three groups of predictors: 'Low social support' (widowed,
      living alone, low social support), 'personal cognitive reserve' (low social
      activity, no leisure exercise, never having married, loneliness and boredom
      proneness), and 'sociodemographic cognitive reserve' (primary education, rural
      domicile). In multivariate analysis, both cognitive reserve clusters, but not
      social support, were independently associated with cognitive function. Loneliness
      and boredom-proneness are associated with reduced cognitive function in older
      age, and cluster with other factors associated with cognitive reserve. Both may
      have a common underlying mechanism in the failure to select and maintain
      attention on particular features of the social environment (loneliness) or the
      non-social environment (boredom-proneness).

PMID- 20677085
TI  - Understanding of stroke and coronary heart disease in the UK: an exploratory
      study.
AB  - It has been suggested by the UK's 2007 National Stroke strategy for England
      (NSSFE) that general population awareness is high for coronary heart disease
      (CHD) but low for stroke. This was investigated in the present study. One hundred
      eighty-two members of the general public completed a questionnaire about
      understanding of stroke/CHD. Data were analysed using ANOVA, t-tests and chi
      square. The main findings were that although members of the general public
      understood some of the main aspects of stroke and CHD, there was more awareness
      of general facts about CHD than stroke but symptoms of stroke were better
      identified compared to CHD. Therefore, our findings only partially supported the
      NSSFE view.

PMID- 20677086
TI  - Confidence matters: a Self-Determination Theory study of factors determining
      engagement in self-management support practices of UK clinicians.
AB  - Within a national quality improvement programme for self-management of long-term
      conditions, we surveyed clinicians working with patients with diabetes, chronic
      obstructive pulmonary disease, musculoskeletal pain and depression. We applied
      the Self-Determination Theory framework to explore what factors can facilitate
      and impede the clinicians' engagement in clinical self-management support (SMS),
      patient centredness and organizational support for self-management. We also
      investigated whether attending professional training for clinicians in the
      practice of self-management (SM) increases motivation to support SM and reported
      use of SM practices. The study included 482 clinicians who were surveyed once
      (cross-sectional design) and 114 clinicians who were surveyed before and after
      training (longitudinal cohort). We found that the high level of satisfaction of
      competence need predicts practising SMS in all three areas (clinical SMS: beta
      coefficient = 0.21; p < 0.0001; patient centredness: beta coefficient = 0.50; p <
      0.001; organizational SMS: coefficient = 0.20; p < 0.0001). Internalized
      regulation to support SMS increases engagement in clinical and organizational
      SMS. Upon comparing the two samples we explored the possible predictors of
      clinicians' self-referring to attend the training. Clinicians who volunteer to
      attend the training spend more time working directly with patients with long-term
      conditions (chi(2) = 4.8; df = 1; p = 0.02), had less previous relevant training
      (chi(2) = 4.77; df = 1; p = 0.02), and they have less autonomy to support SM (t =
      5.0; df = 476; p < 0.0001). However, they report more engagement in patient
      centred practices (t = 1.9; df = 585; p = 0.05). These factors are a good fit
      with the aims of the programme. We confirmed that attending the training had a
      significant, positive impact on clinicians' engagement in clinical SMS and
      patient centredness, as well as their overall confidence to support SM. We
      conclude that to facilitate clinicians to practice SMS it is very important to
      provide relevant professional training, professional support and incentives to
      foster clinicians' perceptions of their competence in relation to these
      practices. Organizations should develop a culture that values SMS, offer training
      to clinicians to enhance their sense of competence to effectively deliver SMS and
      support clinicians in finding their own way of supporting SM; in other words to
      create an optimal context to internalize regulation to support SM.

PMID- 20677089
TI  - Strategies for long-term expression of transgenes in the respiratory epithelium.
AB  - Lung gene therapy is being developed to treat acute and chronic airway diseases,
      and many viral and non-viral gene transfer vectors have been evaluated in the
      airway epithelium lining the nose and lung. Stem cells have not been clearly
      defined in the airways and, currently, it is only possible to target progenitor
      cells to proliferate and repair the epithelium after inducing epithelial damage.
      However, the majority of airway epithelial cells are slowly dividing or
      terminally differentiated, thus necessitating repeated administration of gene
      transfer vectors for life-long transgene expression. Many improvements to adeno
      associated virus and lentivirus vectors have led to increased airway transduction
      efficiencies, although achieving consistent repeated administration remains
      problematic because of immune system activation. Non-viral vectors appear to be
      less efficient, but can be successfully re-administered. The modification of
      plasmid sequences also offers maximum flexibility in increasing and extending the
      duration of transgene expression in the airways. This review describes recent
      developments in achieving persistent transgene expression in the airways by
      specifically targeting the cells of the respiratory epithelium lining the nose
      and lung.

PMID- 20677090
TI  - Potentiating oncolytic viruses by targeted drug intervention.
AB  - Oncolytic virus therapy (OVT) is a promising treatment modality for cancer that
      uses tumor-specific defects to target cancer cells selectively. An increasing
      number of replicating viruses has been demonstrated to cure cancer in a diverse
      set of animal models. Accordingly, many such viruses have entered the clinic,
      with several phase III clinical trials having recently been approved or
      initiated. As with most modalities that target cancer, which is a disease
      characterized by pronounced cellular heterogeneity and genetic instability, it is
      anticipated that the efficacy of OVT will benefit from combination therapy.
      During the past 5 years, significant efforts have been invested in evaluating the
      combination of OVT and existing chemotherapies, as well as rationally designing
      chemical-OVT combinations. This review provides an update on these two approaches
      to augmenting OVT, and suggests that unbiased, high-throughput genetic and
      chemical screening technologies may both compliment and offer several advantages
      when combined with these approaches in the pursuit of effective chemical-OVT
      combinations for the treatment of cancer.

PMID- 20677091
TI  - Design of virotherapy for effective tumor treatment.
AB  - The use of viruses as therapeutic agents against cancer is an old concept that
      has had a significant revival in the past two decades, in parallel with advances
      in methods to modify viral genomes genetically. From the initial stage of proof
      of concept, the field of virotherapy quickly progressed to the clinical setting,
      where serious limitations, yet promising opportunities, were identified. After
      demonstrating good safety profiles in humans, the objective in virotherapy has
      become to improve the efficacy of oncolytic viruses. Virotherapy approaches
      include incorporating therapeutic genes, evaluating alternative viruses with
      stronger oncolytic potential, employing new methods to improve biodistribution,
      and establishing greater insight into the influence of the immune system on both
      the success and failure of therapies. This review summarizes the most significant
      advances in recent years in the design of virotherapy for effective tumor
      treatment.

PMID- 20677092
TI  - Blood compatibility of enveloped viruses.
AB  - A significant limitation to the use of viruses as systemic vectors is the
      susceptibility of the vector to inactivation and clearance by various blood
      components. Despite much focus on antibodies as the primary neutralizing
      molecules in blood, other mechanisms inactivate and clear virus particles from
      the bloodstream in both naive and pre-immune hosts. This review provides an
      overview of the major blood components that interact with enveloped viruses. The
      mechanisms of action of these blood components by which virus particles are
      inactivated are also discussed. In addition, important blood components that act
      as barriers to the systemic delivery of therapeutic viruses are identified, and
      recent advances in overcoming these barriers are highlighted. Particular
      attention is given to the field of oncolytic virotherapy in which adequate
      intravenous virus delivery is critical for therapeutic success.

PMID- 20677093
TI  - Adenovirus-based therapy for prostate cancer.
AB  - Prostate cancer is the second leading cause of cancer-related death in men in the
      Western world, despite efforts toward improving treatment strategies and earlier
      detection of this disease. A promising and relatively novel drug platform is
      virotherapy, which has demonstrated potent and selective antitumor efficacy in
      cancer cell lines and in preclinical in vivo tumor models, accompanied by minimal
      toxicity to normal cells. Safety and limited toxicity has also been demonstrated
      in many clinical trials targeting various solid cancers. Results from early-stage
      trials in patients with hormone-refractory prostate cancers have revealed
      potential efficacy following intraprostatic or intravenous delivery of
      replication-selective oncolytic viruses in combination with chemotherapeutics or
      radiation therapy. This review describes the most promising developments in
      virotherapy for prostate cancer, focusing on replication-selective adenoviral
      mutants as multimodal therapeutic agents.

PMID- 20677094
TI  - Stem cells for the treatment of heart failure.
AB  - An increasing number of clinical trials are enrolling patients in studies
      designed to examine the safety and efficacy of autologous stem cells for cardiac
      repair. Recent reports suggest that most patients receiving autologous cell-based
      therapies after myocardial infarction, or as a treatment for ischemic
      cardiomyopathy, benefit from a modest increase in global left ventricular
      function. Despite a significant amount of variability in efficacy reported among
      different treatment centers, most studies demonstrate an improvement in the
      ejection fraction that ranges between 2 and 7% after stem cell treatment. The
      validation of long-term clinical benefit will first require well-controlled
      studies in appropriate preclinical animal models to develop procedures that
      enhance cell retention, integration and viability. This review highlights new
      developments that will benefit long-term cardiomyocyte survival and function of
      human cardiovascular progenitors as a prelude to achieving clinically significant
      outcomes in stem cell therapies for cardiac repair.

PMID- 20677095
TI  - Adipose-derived stem and stromal cells for cell-based therapy: current status of
      preclinical studies and clinical trials.
AB  - The potential use of stem cell-based therapies for the repair and regeneration of
      various tissues and organs offers a paradigm shift that may provide alternative
      therapeutic solutions for several diseases. The clinical use of either embryonic
      stem cells or induced pluripotent stem cells remains limited because of cell
      regulations, ethical considerations and the requirement for genetic manipulation,
      although these cells are theoretically highly beneficial. Adipose-derived stem
      cells (ASCs) appear to be an ideal population of stem cells for practical
      regenerative medicine, given that they are plentiful, of autologous tissue origin
      and thus non-immunogenic, and are more easily available because of minimal
      ethical considerations. Although ASCs originate from mesodermal lineages, recent
      preclinical studies have demonstrated that the use of ASCs in regenerative
      medicine is not limited to mesodermal tissue, but can also extend to both
      exodermal and endodermal tissues and organs. This review summarizes and discusses
      current preclinical and clinical data on the use of ASCs in regenerative medicine
      and discusses the future applications of such cell-based therapies.

PMID- 20677096
TI  - Encapsulated cells to focus the metabolic activation of anticancer drugs.
AB  - One of the first strategies for cancer gene therapy was the use of suicide
      gene/prodrug combinations, originally delivered to tumor cells using viral
      vectors. A major limitation of this approach was the inefficiency of suicide gene
      delivery. An alternative strategy, in which the suicide genes are physically
      juxtaposed to the tumor, involves the implantation of encapsulated, genetically
      modified cells. Cell encapsulation technologies were originally developed for the
      treatment of acquired and genetic diseases, such as diabetes. In the application
      of this technology for the treatment of tumors, cells that are genetically
      modified to overexpress suicide genes are encapsulated and implanted near solid
      tumors; this process is then followed by systemic prodrug administration. This
      review discusses the various cells types, suicide genes and prodrugs that have
      been used in preclinical and clinical trials, as well as the data that have been
      obtained from these studies. Future improvements for the production of second
      generation approaches are also discussed.

PMID- 20677097
TI  - Subcutaneous administration of biotherapeutics: current experience in animal
      models.
AB  - In recent years, many peptide- and protein-based biotherapeutics have been
      approved for subcutaneous (SC) delivery. The mechanisms and factors affecting the
      uptake and distribution of such large molecules following SC administration are
      not well understood. This review outlines the factors influencing uptake,
      transport, distribution and species differences following the SC administration
      of biotherapeutics; improved understanding of these factors will facilitate the
      appropriate selection of animal models and improve predictivity for the
      bioavailability of drugs in humans. Morphological differences between species,
      such as the presence or absence of the panniculus carnosus muscle, may have
      significant effects on SC delivery. Following SC administration, small molecules,
      peptides and small proteins (< or = 16 kDa) primarily diffuse through the blood
      vessel walls directly into capillaries, whereas large molecules are taken up into
      the more porous lymphatics. Critical parameters that may impact the availability
      in blood of compounds administered SC, other than molecular weight, include host
      related factors, such as animal motility, age and gender, structural and
      functional characteristics of the SC interstitium and the lymphatics, and
      extrinsic factors, such as anesthesia, injection technique, potential
      precipitation or degradation at the injection site, and the use of SC delivery
      technology. A review of regulatory approval information for SC administered
      biotherapeutics is provided for comparison. Careful control of parameters during
      SC administration will reduce inter-individual and inter-species variability.

PMID- 20677098
TI  - tgAAG76, an adeno-associated virus delivered gene therapy for the potential
      treatment of vision loss caused by RPE65 gene abnormalities.
AB  - The gene therapy vector tgAAG76 (rAAV 2/2.hRPE65p.hRPE65) is in joint development
      by Targeted Genetics Corp, Moorfields Eye Hospital and the University of London.
      The vector is a recombinant adeno-associated virus vector that contains the human
      RPE65 gene under the control of the human RPE65 promoter region and the bovine
      growth hormone polyadenylation signal. The vector was designed for administration
      into the subretinal space of patients affected by a hereditary blinding disorder,
      Leber congenital amaurosis type 2, which is caused by mutations in the RPE65
      gene. Interim results from an ongoing phase I/II clinical trial assessing tgAAG76
      in three patients with Leber congenital amaurosis type 2 were considered to
      accomplish the primary outcome of the trial, which was the safety of the
      procedure, with no severe side effects observed to date. One of the three
      patients had a significant increase in sensitivity to light and the better
      capacity to ambulate an obstacle course under dim light conditions compared with
      baseline. Completion of the clinical trial was anticipated in the second half of
      2010.

PMID- 20677099
TI  - PRO-051, an antisense oligonucleotide for the potential treatment of Duchenne
      muscular dystrophy.
AB  - PRO-051 (GSK-2402968), being developed by GlaxoSmithKline plc, under license from
      Leiden University Medical Center and Prosensa Therapeutics BV, is a 2'-O-methyl
      phosphorothioate antisense oligonucleotide for the potential treatment of
      Duchenne muscular dystrophy (DMD). The PRO-051 oligonucleotide sequence induces
      skipping of exon 51 of the dystrophin gene by binding to a sequence within the
      dystrophin pre-mRNA and masking the exon inclusion signals that are used for
      splicing. Removal of exon 51 from an exon 45 to 50, 47 to 50, 48 to 50, 49 to 50,
      50, 52 or 52 to 63 deleted transcript allows restoration of the open reading
      frame and synthesis of an internally truncated, semi-functional dystrophin
      protein. By targeting exon 51, approximately 13% of patients with DMD could be
      treated, the largest proportion of patients that could benefit from targeting a
      single dystrophin exon. A proof-of-concept clinical trial of PRO-051 in patients
      with DMD demonstrated that a single intramuscular administration of PRO-051
      induced exon skipping within muscle fibers adjacent to the injection site, while
      biopsies revealed dystrophin expression in treated but not control muscle fibers.
      At the time of publication, a phase I/IIa trial to evaluate subcutaneous delivery
      of PRO-051 had been completed, although full results were yet to be published.

PMID- 20677100
TI  - AMG-386, a selective angiopoietin-1/-2-neutralizing peptibody for the potential
      treatment of cancer.
AB  - The VEGF/VEGFR and angiopoietin/Tie-2 signaling pathways are important in the
      process of vascular endothelial growth (angiogenesis) and in the maintenance of
      tumor-associated blood vessels. While there are several agents targeting the
      VEGF/VEGFR signaling pathway, there are none available that target the
      angiopoietin/Tie-2 signaling pathway. The first such agent to reach clinical
      trials is AMG-386 (2xCon4C), being developed by Amgen Inc and licensed in Japan
      to Takeda Bio Development Center Ltd. AMG-386 is an anti-angiopoietin peptibody
      comprising a peptide with angiopoietin-binding properties that is fused to the Fc
      (crystallizable fragment) region of an antibody and inhibits the interaction
      between the ligands angiopoietin-1 and angiopoietin-2 with the Tie-2 receptor.
      AMG-386 significantly inhibited the growth of tumors in a variety of mouse
      xenograft models. In phase I trials of AMG-386 as a monotherapy or in combination
      with chemotherapy in patients with advanced solid tumors, AMG-386 demonstrated
      only mild toxicities, and one complete response and several partial responses
      were achieved in patients. Phase II trials of AMG-386 in combination with
      chemotherapy were ongoing in a variety of solid tumors, including breast,
      ovarian, colorectal, gastric and renal cell cancers. If safe and effective, AMG
      386 could be an exciting addition to other antiangiogenic therapies in solid
      tumors.

PMID- 20677101
TI  - [Ankylosing spondylitis: imaging findings in the axial skeleton].

PMID- 20677111
TI  - [Quality of the reporting of diagnostic accuracy studies: STARD (Standards for
      the Reporting of Diagnostic accuracy studies)].

PMID- 20677114
TI  - [Regulated performance volumes for practices with below average number of cases-
      special regulation for an exceptional reason for low number of cases].

PMID- 20677115
TI  - [New: DGRW update on selected rehab indications].

PMID- 20677116
TI  - [DGRW update: rehabilitation in cardiovascular diseases. what's new in cardiac
      rehabilitation?].
AB  - BACKGROUND: A quality goal of medical rehabilitation is ongoing and continuous
      development of service standards orientated by the patient and new research
      findings. Because of the stark increase of research findings in the field of
      rehabilitation, it becomes difficult for the responsible rehabilitation providers
      to keep up to date on new findings and to realize the transfer of knowledge.
      Hence, the aim was to establish a literature research which surveys current
      national and international results in cardiac rehabilitation. METHODS: The
      literature search was undertaken using the electronic databases OVID and includes
      publications from 2009 and the first 2 months of 2010. The selection of studies
      was performed in a team of experts based on the criteria of relevance, usefulness
      and methodological quality of research for rehabilitation. RESULTS: 26 primary
      sources were selected, mainly focusing the fields "Cardiac rehabilitation:
      indications", "Risk factors and prevention", "Job-related reintegration",
      "Rehabilitation of specific medical disease patterns" and "New rehabilitation
      models". CONCLUSION: The studies examined show very clearly that cardiac patients
      can benefit from participation in cardiac rehabilitation treatment and that
      prevention represents a central task of medical care in the long-term treatment
      of coronary diseases. There is a need for further research, especially concerning
      the topics "New rehabilitation models" and "Job-related reintegration". The DGRW
      Update intends to depict current developments and to promote evidence-based
      medicine in rehabilitation.

PMID- 20677117
TI  - [DGRW-update: medical rehabilitation with children and adolescents].
AB  - Medical rehabilitation of chronically ill children and adolescents is
      characterised by interdisciplinary methods including parents' participation.
      Research in this field leads to specific evaluation approaches and corresponding
      measurement procedures. There are guidelines for many important indications, and
      the effectiveness of various indications for therapy and training programmes is
      proven. The effectiveness of medical rehabilitation (e. g. for asthma) has been
      documented in multi-centre studies.

PMID- 20677118
TI  - [DGRW-update: exercise therapy in medical rehabilitation--effects, quality,
      perspectives].
AB  - Exercise therapy constitutes the better part of rehabilitative treatment.
      However, in rehabilitation research the scientific analysis of exercise therapy
      only plays a minor role. Taking the theoretical model of rehabilitation and the
      International Classification of Functioning, Disability and Health (ICF) into
      account, we propose a heuristic model of aims and effects of exercise therapy and
      define a system of methodological target setting. This system offers a background
      for an expanded scientific discussion about biopsychosocial determinants and
      effects of exercise therapy as well as quality development and the evaluation of
      exercise treatment concepts within and across indications in the context of
      multimodal medical rehabilitation.

PMID- 20677119
TI  - [Prediction models on return to work of rehabilitants following vocational
      training programme participation].
AB  - PURPOSE: Vocational rehabilitation aims at vocational reintegration of disabled
      persons. Three different types of rehabilitative vocational training programmes -
      i. e., vocational retraining in Berufsforderungswerken (vocational rehabilitation
      centres), in-plant vocational retraining according to the German dual system of
      initial vocational training, and vocational continuation courses - were explored
      concerning subsequent vocational reintegration of the participants. METHODS: The
      rehabilitants were given standardized questionnaires at the beginning (T1) and 1
      year after their vocational training (T5). Between 61% and 64% of those
      rehabilitants who had completed their vocational training took part in the final
      postal survey 1 year after the vocational rehabilitation (T5). Data of the T1
      questionnaires were used for prediction models concerning successful vocational
      reintegration of the rehabilitants one year after their vocational training.
      RESULTS: Important differences were found between the participants of the three
      rehabilitation programmes in socio-demographic, health-related and psychological
      characteristics, due to specific statutory criteria for assignment of disabled
      persons to the different forms of vocational rehabilitation. 1 year after the
      vocational training, 55% of the rehabilitants of both forms of vocational
      retraining (external, in-plant) and 31% of the participants of vocational
      continuation courses were employed in the first labour market. For all 3 forms of
      vocational rehabilitation programmes, 3 significant predictors were found
      concerning successful vocational reintegration of the rehabilitants: the local
      job market at the participants' residence, specific health complaints (pain or
      sleep disturbances) and social support. Other significant predictors were a
      number of psychological, sociological, and occupation-related biographical
      variables. DISCUSSION: A set of variables proved to be relevant predictors for
      vocational reintegration of rehabilitants 1 year after the end of vocational
      retraining and continuation measures. Some of these variables could be used
      practically for specific interventions to increase chances of vocational
      reintegration for participants of vocational rehabilitation measures.

PMID- 20677120
TI  - [Medical inpatient rehabilitation influences on self-esteem and self-efficacy of
      chronically ill adolescents].
AB  - BACKGROUND: In this article the development of self-esteem and self-efficacy in
      adolescents with chronic physical illness with and without psychological symptoms
      is measured over one year, following a medical inpatient rehabilitation treatment
      of four to six weeks. Gender- and diagnosis-related differences are analyzed.
      MATERIALS AND METHODS: 243 chronically ill adolescents were interviewed at the
      beginning of their rehabilitation treatment. After one year data of 99
      chronically ill adolescents are available (age: M=14.6; SD=1.70), 50 boys. Self
      esteem was measured using the revised Rosenberg Self-Esteem Scale. The revised
      Allgemeine Selbstwirksamkeitsskala was chosen for assessing self-efficacy at
      school and other social contexts. At the beginning of rehabilitation,
      psychological symptoms were identified using the German version of the Strengths
      and Difficulties Questionnaire. RESULTS: Therapy of chronically ill adolescents
      in medical rehabilitation affects their self-esteem positively, with differences
      in self-esteem found between adolescents who show clinically relevant
      psychological symptoms and those who do not. Only minor changes are however
      noticed in ratings of self-efficacy at school and other social contexts. Gender-
      and diagnosis-related differences have not been found.

PMID- 20677121
TI  - [Report of the 8th national ICF user conference held on March 10, 2010 in
      Leipzig].

PMID- 20677122
TI  - ["Effects of the convention on the rights of persons with disability on
      rehabilitation in Germany--impact and perspectives"].

PMID- 20677123
TI  - Pulmonary function in children after open water SCUBA dives.
AB  - An increasing number of children and adolescents is diving with Self-Contained
      Underwater Breathing Apparatus (SCUBA). SCUBA diving is associated with health
      risks such as pulmonary barotrauma, especially in children and in individuals
      with airflow limitation. As no data has been published on the effects of open
      water diving on pulmonary function in children, the objective of this study was
      to evaluate the effects of SCUBA dives on airflow in children. 16 healthy
      children aged 10-13 years underwent spirometry and a cycle-exercise challenge
      while breathing cold air. They subsequently performed dives to 1-m and 8-m depth
      in random order. Pulmonary function was measured before and after the exercise
      challenge and the dives. There were statistically significant decreases in FEV1,
      FVC, FEV1/FVC, MEF25 and MEF50 after the cold-air exercise challenge and the
      dives. Changes in lung function following the exercise challenge did not predict
      the responses to SCUBA diving. In 3 children the post-dive decrements in FEV1
      exceeded 10%. These children had a lower body weight and BMI percentile. SCUBA
      diving in healthy children may be associated with relevant airflow limitation. A
      low body mass might contribute to diving-associated bronchoconstriction. In the
      majority of subjects, no clinically relevant airway obstruction could be
      observed.

PMID- 20677124
TI  - Slackline training for balance and strength promotion.
AB  - The prevalence of sustaining a sport injury is high in adults. Deficits in
      postural control/muscle strength represent important injury-risk factors. Thus,
      the purpose of this study was to investigate the impact of a specific type of
      balance training, i. e. slackline training, followed by detraining on balance and
      strength performance. Twenty-seven adults participated in this study and were
      assigned to an intervention (age 22.8+/-3.3 yrs) or a control group (age 23.9+/
      4.4 yrs). The intervention group participated in 4 weeks of slackline training on
      nylon webbings. Detraining lasted 4 weeks. Tests included the measurement of (A)
      total centre of pressure displacements during one-legged standing on a balance
      platform and during the compensation of a perturbation impulse, (B) maximal
      torque and rate of force development (RFD) of the plantar flexors on an
      isokinetic device, and (C) jumping height on a force platform. After training, no
      significant interaction effects were observed for variables of static/dynamic
      postural control, maximal torque, and jumping height. Training-induced
      improvements were found for RFD. After the withdrawal of the training stimulus,
      RFD slightly decreased. Given that the promotion of balance and strength is
      important for injury prevention, changes in RFD only might not be sufficient to
      produce an injury-preventive effect.

PMID- 20677125
TI  - Quality of life and obesity class relationships.
AB  - The aim of this study was to quantify the impact of obesity class on Health
      Related Quality Of Life (HRQOL) and Total daily Energy Expenditure (TEE). 69
      obese individuals were self-selected to 1 of 3 groups based upon Body Mass Index
      (BMI). Anthropometric parameters (height, weight, waist and hip circumference,
      fat mass, lean body mass), biological parameters (high density lipoprotein, low
      density lipoprotein, triglycerides, glycaemia, total cholesterol), and resting
      energy expenditure were assessed for each group. The Short Form Health Survey (SF
      36) questionnaire and Hospital Anxiety Depression (HAD) scale were used to
      measure HRQOL, and TEE was estimated by Kurpad's method. Class 3 obesity was
      associated with greater impairment of the physical aspects of the SF-36 (37.2+/
      11.3), greater depression risk (8.2+/-4.1), and higher TEE (30.0+/-7.9 Kcal.day (
      1).kg (-1)) than the lower obesity classes. No difference was observed among the
      3 groups in the mental and psychosocial aspects of HRQOL. Impaired physical
      functioning was correlated with fat mass, age, waist circumference, glycaemia
      control and bodily pain. TEE was positively correlated with BMI, weight, fat mass
      and lean body mass. The obesity class had a negative impact on the physical
      health aspect of HRQOL, depression risk and energy expenditure. These impairments
      were associated with excess fat mass, waist circumference and glycaemia
      parameters.

PMID- 20677126
TI  - Young adults with Fetal Alcohol Syndrome (FAS): social, emotional and
      occupational development.
AB  - BACKGROUND: Maternal alcohol abuse during pregnancy causes physical, cognitive
      and behavioural impairments in the child. Deficits are irreversible and persist
      into adulthood. It was the objective of this study to investigate the specific
      problems and challenges faced by young adults with Fetal Alcohol Syndrome (FAS).
      PATIENTS: We examined the biographical development and living situation of 60
      adult patients with FAS. In their childhood, all the patients had been diagnosed
      with FAS in the Muenster University hospital. METHODS: Using a structured
      interview, we asked for the occupational career, health and social problems as
      well as the current living conditions of the patients. RESULTS: Most patients
      lived in dependent circumstances. The occupational development was characterized
      by disruption and failure, and severe social problems were common in patients. 3
      in 4 patients were victims of physical and sexual abuse. CONCLUSIONS: Due to the
      variety of impairments caused by prenatal alcohol exposure and the persisting
      inability to live independently, adults with FAS need intense care, support and
      assistance.

PMID- 20677129
TI  - CT features of intrathoracic gossypiboma (textiloma).
AB  - Here, we present chest radiography and computed tomography (CT) findings for
      three cases of mediastinal and pleural gossypiboma. Radiological manifestations
      varied according to the locations and chronicities of the gauze sponges and the
      types of reactions that they caused. CT analysis readily diagnosed gossypibomas
      in the early postoperative period by showing well-defined mediastinal- or pleural
      based masses with hyperdense rims and central air bubbles. However, one patient
      presented in the late postoperative period, and a CT scan revealed a well
      defined, solid pleural mass that was devoid of air bubbles; a correct diagnosis
      could not be established and the patient had to be reoperated on. Radiologists
      should be aware of different manifestations of this rare condition in cases of
      prior thoracic surgery and persistent respiratory symptoms.

PMID- 20677130
TI  - Imaging of non-neoplastic intratesticular masses.
AB  - The use of high-frequency ultrasound is increasing for the treatment of cystic,
      vascular, and solid non-neoplastic intratesticular masses. Cystic lesions
      examined include simple testicular cysts, tunica albuginea cysts, epidermoid
      cysts, tubular ectasia of rete testis, and intratesticular abscesses. Vascular
      lesions examined include intratesticular varicocele and intratesticular
      arteriovenous malformations. Solid lesions examined include fibrous pseudotumor
      of the testis, focal or segmental testicular infarct, fibrosis of the testis,
      testicular hematoma, congenital testicular adrenal rests, tuberculoma, and
      sarcoidosis. Gray-scale and color-flow Doppler sonography facilitate the
      visualization of the benign characteristics of the lesions. Magnetic resonance
      imaging can also help as a problem-solving modality in some cases.

PMID- 20677131
TI  - Mammography and mammographic screening: are female patients at a teaching
      hospital in Lagos, Nigeria, aware of these procedures?
AB  - PURPOSE To determine the level of awareness of mammography and mammographic
      screening amongst women in Lagos, Nigeria. MATERIALS AND METHODS A structured
      questionnaire was administered to 555 consecutively recruited women who visited
      various clinics at the Lagos State University Teaching Hospital, Ikeja, between
      January 2009 and June 2009. RESULTS The mean age of respondents was 38.16 +/- 9
      years, and the majority (59.6%) had a tertiary education. A family history of
      breast cancer was present in 33 (6.0%) women, less than 20% of whom had undergone
      mammography. Only 20% of all subjects were aware of the recommendation that they
      should receive routine mammography and mammographic screenings on an annual or
      biannual basis, depending on their age, and of the side effects associated with
      the procedure. The mass media was women's main source of information regarding
      these procedures. The majority (67.6%) of participants confirmed that they
      performed breast self-examinations, though less than 5% of them had had their
      breasts examined by mammography. CONCLUSION This study revealed a rather low
      level of awareness about mammography and mammographic screening, indicating the
      need to educate women about the risk of breast cancer and the importance of
      screening as a tool for the early detection and treatment of this condition.

PMID- 20677132
TI  - Intraosseous hemangioma of the rib mimicking an aggressive chest wall tumor.
AB  - Bone hemangiomas are extremely rare in the ribs, with only a handful of cases
      reported in the literature. A case of a rib hemangioma is presented in which the
      pre-resection diagnosis was an aggressive chest wall tumor. The plain film, CT,
      MRI and bone scan features of the lesion were reviewed with the pathological
      correlation. On imaging, the lesion was expansile and lytic, and it also had fine
      bony trabeculae. The lesion also demonstrated growth beyond a disrupted bony
      cortex, suggesting malignancy. This case report adds to the literature on this
      rare condition and discusses the issues in the diagnosis of chest wall tumors.

PMID- 20677134
TI  - Genetic differences between strains of Biomphalaria glabrata (Planorbidae) that
      are susceptible and unsusceptible to schistosomiasis.
AB  - Despite the implementation control programs, schistosomiasis continues to spread
      throughout the world. Among modern control strategies, vector control is
      currently being emphasized. Within this context, analysis of the genetic
      variability of intermediate host snails (Biomphalaria spp) is important because
      it allows identification of specific sequences of the genome of this mollusk
      related to susceptibility/resistance to Schistosoma mansoni infection. We
      investigated Brazilian albino (non-pigmented) and pigmented (wild type) strains
      of Biomphalaria glabrata; these strains differ in their susceptibility to S.
      mansoni infection. Genetic variability was studied by RAPD-PCR using different
      random primers. The electrophoretic patterns resulting from amplification showed
      specific polymorphic markers for the albino and pigmented strains of B. glabrata.
      This information will help in the identification and isolation of genes
      specifically related to susceptibility, demonstrating that RAPD-PCR is an
      appropriate and efficient methodological approach for analysis of the genetic
      variability of schistosomiasis vectors.

PMID- 20677133
TI  - Frequency of ABO blood group system polymorphisms in Plasmodium falciparum
      malaria patients and blood donors from the Brazilian Amazon region.
AB  - We investigated the ABO genotypes and heterogeneity of the O alleles in
      Plasmodium falciparum-infected and non-infected individuals from the Brazilian
      Amazon region. Sample collection took place from May 2003 to August 2005, from P.
      falciparum malaria patients from four endemic regions of the Brazilian Amazon.
      The control group consisted of donors from four blood banks in the same areas.
      DNA was extracted using the Easy-DNA(TM) extraction kit. ABO genotyping was
      performed using PCR/RFLP. There was a high frequency of ABO*O01O01. ABO*AO01 was
      the second most frequent genotype, and the third most frequent genotype was
      ABO*BO01. There were low frequencies of the ABO*O01O02, ABO*AA, ABO*AB, ABO*BB,
      and ABO*O02O02 genotypes. We analyzed the alleles of the O phenotype; the
      O(1variant) allele was the most frequent, both in malaria and non-malaria groups;
      consequently, the homozygous genotype O(1)(v)O(1)(v) was the most frequently
      observed. There was no evidence of the homozygous O(2) allele. Significant
      differences were not detected in the frequency of individuals with the various
      alleles in the comparison of the malaria patients and the general population
      (blood donors).

PMID- 20677135
TI  - Isolation of retro-transcribed RNA from in vitro Mycosphaerella fijiensis
      infected banana leaves.
AB  - High polyphenol and polysaccharide levels in plant tissues such as banana fruit
      and leaves constitute a significant challenge to the extraction of sufficient
      amounts of high-quality RNA required for cDNA library synthesis and molecular
      analysis. To determine their comparative effectiveness at eliminating
      polyphenols, polysaccharides and proteins, three protocols for RNA extraction
      from in vitro banana plantlet leaves were tested: Concert(TM) Plant RNA isolation
      kit, a small-scale protocol based on Valderrama-Chairez, and a modified version
      of the Valderrama-Chairez protocol. RNA quantity and purity were evaluated by UV
      spectrophotometry using DEPC-treated water and Tris-HCl, pH 7.5. Purity was
      greater using Tris-HCl. The Concert(TM) Plant protocol produced the poorest
      quality RNA. Reverse transcription into cDNAs from RNA isolated from in vitro
      banana plantlet leaves infected with Mycosphaerella fijiensis using the modified
      Valderrama-Chairez protocol, followed by PCR using primers designed against gamma
      actin from banana and M. fijiensis, yielded products of the anticipated size. In
      addition, this protocol reduced the processing time, lowered costs, used less
      expensive equipment, and could be used for other plants that have the same
      problems with high polyphenol and polysaccharide levels.

PMID- 20677136
TI  - Genetically modified animals for use in research and biotechnology.
AB  - Transgenic animals are used extensively in the study of in vivo gene function, as
      models for human diseases and in the production of biopharmaceuticals. The
      technology behind obtaining these animals involves molecular biology techniques,
      cell culture and embryo manipulation; the mouse is the species most widely used
      as an experimental model. In scientific research, diverse models are available as
      tools for the elucidation of gene function, such as transgenic animals, knockout
      and conditional knockout animals, knock-in animals, humanized animals, and
      knockdown animals. We examined the evolution of the science for the development
      of these animals, as well as the techniques currently used in obtaining these
      animal models. We review the phenotypic techniques used for elucidation of
      alterations caused by genetic modification. We also investigated the role of
      genetically modified animals in the biotechnology industry, where they promise a
      revolution in obtaining heterologous proteins through natural secretions, such as
      milk, increasing the scale of production and facilitating purification, thereby
      lowering the cost of production of hormones, growth factors and enzymes.

PMID- 20677138
TI  - [Sperm chromosome analysis and preimplantation genetic diagnos is in an infertile
      male with mosaic trisomy 18].
AB  - OBJECTIVE: To analyze the numerical aberration rate of X, Y and chromosome 18 in
      sperms from an oligozoospermic male with mosaic trisomy 18 and to perform
      preimplantation genetic diagnosis (PGD) for the couple. METHODS: G-banding and
      fluorescence in situ hybridization (FISH) were performed on metaphase chromosome.
      Sperm was analyzed in three-color FISH with a probe mixture containing CEP18,
      CEPY and Tel Xq/Yq. A healthy man with normal semen parameters was used as
      control. RESULTS: Significant difference in the rates of disomy for chromosome 18
      (0.63% vs. 0.16%) and the gonosomes (0.945% vs. 0.35%) and diploidy (0.87% vs.
      0.31%) was found in the spermatozoa between the patient and the control. After
      four embryos were biopsied in one PGD cycle, two embryos with XY1818 and XX1818
      were selected for implanting and clinical pregnancy was ongoing. CONCLUSION:
      Sperm-FISH allows further understanding of aneuploidy rate and accurate genetic
      counseling. FISHPGD was effective for patient with mosaic trisomy 18.

PMID- 20677137
TI  - [Cytogenetic and molecular genetic study of a case with 8p inverted duplication
      deletion syndrome].
AB  - OBJECTIVE: To define the origin and the precise location of the aberrant
      fragments on the short arm of the chromosome 8 in a mentally retarded boy, and to
      understand the mechanism, the characteristic clinical features and the recurrent
      risk associated with this abnormality. METHODS: High-resolution chromosomal
      banding was performed to analyze the karyotype of the patient and his parents,
      array comparative genomic hybridization (array-CGH) was employed to investigate
      the precise location of the aberrant fragments, and quantitative real-time PCR
      was used to confirm the results. RESULTS: The rearranged chromosome 8 in the
      patient was inverted and duplicated for region 8p11.2-p23.1, and deleted for
      region 8p23.1-pter. In between, a 5.70 Mb single copy region was present, which
      was delimited by the two olfactory receptor (OR) gene clusters. CONCLUSION: This
      is a case of classic inv dup del(8p) syndrome, which is characterized by severe
      mental retardation, brain malformation and specific facial dysmorphism, and is
      induced by non-allelic homologous recombination (NAHR) between the OR genes on
      8p23.1. Prenatal diagnosis should be performed to monitor the recurrent risk of
      inv dup del(8p), as well as the other three harmful consequences resulted from
      the same NAHR mechanism. To the best of our knowledge, this is the first case of
      inverted duplicated 8p syndrome identified in Mainland China.

PMID- 20677139
TI  - [Identification of VEGFR3 gene mutation in a Chinese family with autosomal
      dominant primary congenital lymphoedema].
AB  - OBJECTIVE: To identify the disease-causing gene in a four-generation Chinese
      family with 9 members affected with primary congenital lymphoedema (PCL, also
      known as Milroy disease). METHODS: Linkage analysis was performed with a few
      microsatellite markers flanking the candidate genetic loci for PCL, including 3
      known genes associated with autosomal dominant PCL. For mutation analysis, VEGFR3
      gene was sequenced with DNA from the proband. Direct DNA sequencing of exon 25 of
      the VEGFR3 gene was performed in all family members. RESULTS: The disease gene in
      the family was mapped to chromosome 5q35.3 with a maximum Lod score of 2.07.
      Direct DNA sequencing of VEGFR3 gene revealed a heterozygous C to T transition at
      nucleotide 3341, resulting in p.Pro1114Leu mutation. The p.Pro1114Leu mutation co
      segregated with all affected individuals in the family. CONCLUSION: This study
      identified a C3341T (p.Pro1114Leu) mutation in the VEGFR3 gene in a Chinese
      family with PCL, provided evidence that VEGFR3 mutation can cause PCL in Chinese.

PMID- 20677140
TI  - [A novel mutation of the PAX6 gene in a Chinese family with aniridia].
AB  - OBJECTIVE: The PAX6 gene encodes a transcriptional regulator involved in
      oculogenesis and other developmental processes such as aniridia, a congenital
      condition characterized by the underdevelopment of the iris of eyes. The function
      of the PAX6 gene in these two conditions is still poorly defined. The purpose of
      this study is to identify the mutation of the PAX6 gene in a Chinese family with
      aniridia. METHODS: Two aniridia patients collected from the family underwent full
      ophthalmologic examination. Genomic DNA was prepared from venous leukocytes of
      the two patients and five healthy individuals in the family, and 100 unrelated
      healthycontrols. Exons 4-13 and their immediate flanking sequences of the PAX6
      gene was analyzed by PCR amplification, direct sequencing, and single-strand
      conformation polymorphism(SSCP). RESULTS: The sequencing result revealed a novel
      PAX6 mutation in the two patients. It was a heterozygous mutation (IVS10+1G>A) at
      the boundary of exon 10 and intron 10. The mutation was also detected by SSCP
      analysis. It was not detected in the healthy relatives and unrelated controls.
      CONCLUSION: Aniridia is an autosomal dominant inheritable disease. A novel PAX6
      gene mutation has been identified in the Northeastern Chinese family with
      aniridia. The genetic analysis suggested that this novel mutation in the PAX6
      gene is capable of causing the classic aniridia phenotype.

PMID- 20677141
TI  - [Mitochondrial DNA mutations in gastric endothelial cells induced by extract of
      helicobacter pylori in vitro].
AB  - OBJECTIVE: To investigate the relationship between the helicobacter pylori (HP)
      infection and the genetic instability of mitochondrial DNA (mtDNA) in human
      gastric adenocarcinoma epithelial cells (AGS). METHODS: After treated with
      extracts of HP11638 (CagA+, VacA+) or Hp11638 mutant strain (CagA+, VacA-), AGS
      cells were collected, and mitochondrial DNA was extracted and Cox-I, Cox-II, Cox
      III, ATPase6, ATPase8 and Cytb genes and the D-Loop region were amplified by PCR
      and then sequenced. RESULTS: The mutation rates of the mtDNA in AGS cells were
      correlated with the extracts of the two HP strains in a concentration- and time
      dependent manner. But the mtDNA mutation rate in AGS cells treated with the
      HP11638 extract was higher than that treated with the Hp11638 mutant extract.
      Total of 616 mutations in D-Loop region were detected, including 489 point
      mutations, 81 insertions and 46 deletions. Among them, 70.9% (437/616) belonged
      to GC to AT and AT to GC transition. Seventeen out of 20 (85%) AGS cells treated
      with extract of HP had mutations in 303PolyC, 16184PolyC and 514CA regions of
      mtDNA D-Loop. No mutation was detected in Cox-I, Cox-II, Cox-III, ATPase6 and
      ATPase8 genes, three point mutations were found in the Cytb gene. CONCLUSION: HP
      can cause the accumulation of mutations in mtDNA, in particular, in the D-Loop
      region, and the VacA participated in the process.

PMID- 20677142
TI  - [Chromosome copy analysis by single-cell comparative genomic hybridization
      technique based on primer extension preamplification and degenerate
      oligonucleotide primed-PCR].
AB  - OBJECTIVE: To establish a single-cell whole genome amplification (WGA) technique,
      in combination with comparative genomic hybridization (CGH), for analyzing
      chromosomal copy number changes, and to explore its clinical application in
      preimplantation genetic diagnosis (PGD). METHODS: Twelve single-cell samples with
      known karyotypes, including 5 chorionic villus samples, 4 human embryonic stem
      cell (hESC) samples and 3 peripheral lymphocyte samples, and 4 single blastomere
      samples carrying chromosomal abnormalities detected by PGD, were collected for
      whole genome amplification by combining primer extension preamplification (PEP)
      with degenerate oligonucleotide primed-PCR (DOP-PCR) amplification. The amplified
      products labeled by red fluorescence were mixed with control DNA labeled by green
      fluorescence, and then the mixture was analyzed by CGH. As a comparison, 10
      single cell samples were amplified by DOP-PCR only and then CGH analysis was
      performed. RESULTS: The amplification using PEP-DOP-PCR was more stable than
      traditional DOP-PCR. The products of PEP-DOP-PCR range from 100 bp to 1000 bp,
      with the mean size being about 400 bp. The CGH results were consistent with
      analyses by other methods. However, only 6 out of 10 single cell samples were
      successfully amplified by DOP-PCR, and CGH analysis showed a high background and
      2 samples showed inconsistent results from other methods. CONCLUSION: PEP-DOP-PCR
      can effectively amplify the whole genome DNA of single cell. Combined with CGH,
      this WGA method can successfully detect single-cell chromosomal copy number
      changes, while DOP-PCR was easy to fail to amplify and amplify inhomogeneously,
      and CGH analysis using this PCR product usually showed high background. These
      results suggest that PEP-DOP-CGH is a promising method for preimplantation
      genetic diagnosis.

PMID- 20677143
TI  - [Association of single nucleotide polymorphisms of PATZ1 gene with azoospermia].
AB  - OBJECTIVE: To study the relationship between the polymorphisms of single
      nucleotide polymorphisms(SNPs) in rs2240424, rs2057951, rs2240427 and rs714909
      loci in the PATZ1 gene and azoospermia. METHODS: The allele and genotype
      frequencies of the four SNPs were investigated in 180 patients with azoospermia
      and 190 normal men as controls by polymerase chain reaction and restriction
      fragment length polymorphism (PCR-RFLP) analysis. The allele and genotype
      frequencies of the four SNPs were investigated in 180 patients with azoospermia
      and 190 normal men as controls by polymerase chain reaction and restriction
      fragment length polymorphism (PCR-RFLP) analysis. RESULTS: The frequencies of
      allele C (35.0% vs. 27.6%, P=0.031) and individuals with allele C (TC+CC) (57.8%
      vs. 46.3%, P=0.027) at the rs2057951 locus in azoospermic patients were
      significantly higher than that in normal men. There was a significant difference
      in distribution of haplotypes of the four SNPs between the two groups (P=0.01).
      Hapoltypes ACAC (11.1% vs. 6.6%, P=0.029) and ACGC (11.2% vs. 5.2%, P=0.003)
      increased significantly in azoospermic patients compared with controls.
      CONCLUSION: The allele C of rs2057951 locus and haplotypes ACAC and ACGC of the
      four SNPs in PTAZ1 gene increased the susceptibility to azoospermia, suggesting
      that PATZ1gene may be associated with azoospermia.

PMID- 20677144
TI  - [Distribution of genetic polymorphisms of serum amyloid protein A1 in healthy
      Chinese Han and Uighur populations in Xinjiang].
AB  - OBJECTIVE: To investigate the genetic polymorphisms of rs2229338 and rs12218 loci
      of serum amyloid protein A1 (SAA1) gene in healthy Chinese Han and Uighur
      populations of Xinjiang. METHODS: The genotypes of the SAA1 gene were detected in
      316 Uighur and 362 Han healthy individuals by polymerase chain reaction and
      restriction fragment length polymorphism (PCR-RFLP). RESULTS: The genotype
      distributions of both populations were in the Hardy-Weinberg equilibrium (both
      P>0.05). The frequencies of AA, AG and GG genotypes of the rs2229338 locus were
      76.6%, 23.4%, and 0 in the Uighurs, and 91.7%, 7.7% and 0.6% in the Hans. There
      was significant difference in distribution of genotypes between the two
      populations (P<0.01). The frequencies of CC, CT and TT genotypes of the rs12218
      locus were 10.1%, 47.5%, and 42.4% in Uighurs, and 3.3%, 34.3% and 62.4% in Hans.
      There was also significant difference in distribution of genotypes between the
      two populations (P<0.01). The A-C and G-T haplotypes were more frequent in the
      Uighur but the A-T haplotype was more common in the Han population, respectively
      (both P<0.01). CONCLUSION: The mutational frequencies of the tagging SNPs in
      rs2229338 and rs12218 loci of theSAA1 gene in the Uighurs may be higher than
      those in Hans.

PMID- 20677145
TI  - [Recent advances in studies on autosomal dominant adult polycystic kidney
      disease].
AB  - Adult polycystic kidney disease (APKD) is a severe autosomal dominant inheritable
      renal disease with high incidence. Because of the late-onset of the disease,
      patients might have transferred the disease gene to the next generation when
      diagnosis is made. Since its pathogenic molecular mechanism is still not
      completely clear and the shortage of effective medicines, the prevention and
      treatment of the disease is still not satisfactory. In the present article, the
      recent advances in the research on the pathogenesis, gene diagnosis and
      management of APKD are reviewed.

PMID- 20677146
TI  - [Research progress in roles of microRNA in polyglutamine diseases].
AB  - Polyglutamine (Poly Q) diseases are a group of neurodegenerative disorders,
      caused by the formation of PolyQ mutants due to trinucleotide repeats expansion
      in coding regions of disease-causing genes, which eventually lead to selective
      neuronal degeneration and death with unclarified pathogenesis. As a new type of
      genetic regulatory factor, microRNA (miRNA) plays an important role in modulating
      gene expression in eukaryote. During the recent years, more attention was paid to
      roles and related mechanism of miRNA involving in neurodegenerative disease,
      especially PolyQ diseases. This review is focused on research progress in roles
      of miRNA in the pathogenesis of PolyQ diseases.

PMID- 20677147
TI  - [Development and genetic polymorphism of abnormal pronuclear zygotes after
      intracytoplasmic sperm injection].
AB  - OBJECTIVE: To compare the development of abnormal pronuclear zygotes after
      intracytoplasmic sperm injection (ICSI) and analyze their genetic polymorphism.
      METHODS: Four hundred and ninety three abnormal pronuclear zygotes after ICSI
      were divided into three groups based on the number of pronuclei: 347
      nonpronuclear oocytes, 71 monopronuclear zygotes and 75 multipronuclear zygotes.
      All of them were cultured in the medium of Vitrolife G5 series(TM). Sixteen short
      tandem repeats (STR) of seven blastocysts were then analyzed by ABI3100. RESULTS:
      The cleavage rate of nonpronuclear group (25.4%) was lower than that of the
      others (P<0.01), the proportion of blocked embryos in nonpronuclear group (48.9%)
      was significantly higher than that of the others (P<0.05), but the blastocyst
      rate showed no significant difference in three groups (P>0.05). The genetic
      polymorphism of the 16 STRs showed that the blastocysts from the nonpronuclear
      and multipronuclear were diploid, and one of the blastocysts from nonpronuclear
      oocyte was Y-bearing. CONCLUSION: The zygotes with abnormal pronuclei after ICSI
      might have development potential, and the blastocysts from nonpronuclear oocytes
      and multipronuclear zygotes could be diploid.

PMID- 20677148
TI  - [Mutation analysis of ATP2C1 gene in a Chinese family with Hailey-Hailey
      disease].
AB  - OBJECTIVE: To study a Chinese pedigree with Hailey-Hailey disease (HHD) and
      identify the ATP2C1 gene mutation in this family. METHODS: All exons of the
      ATP2C1 gene were analyzed with polymerase chain reaction and DNA sequencing in
      all patients of this family and 80 unrelated population-matched controls.
      RESULTS: We identified a nonsense mutation 163C to T, resulting in a premature
      termination codon in ATP2C1 gene. The mutation was not found in normal
      individuals of the family and controls. CONCLUSION: The mutation can affect the
      result of transcription and translation of ATP2C1 gene, and it is firstly
      reported in the Chinese pedigree with HHD.

PMID- 20677149
TI  - [Study on the relationship of the haplotypes of programmed cell death 1 gene and
      ultraviolet history with systemic lupus erythematosus].
AB  - OBJECTIVE: To investigate the relationship of gene polymorphisms of programmed
      cell death 1 gene (PDCD1) and ultraviolet history with systemic lupus
      erythematosus (SLE) among the Han population in the southern region of yangtze
      river in China. METHODS: With a case control design, a total of 159 SLE cases and
      159 controls were enrolled in this study, and single nucleotide polymorphisms
      (SNPs) of the PDCD1 gene were determined by PCR-restriction fragment length
      polymorphism (RFLP). With the aid of the logistic regression model, the effect of
      gene polymorphism, environmental factor and the interaction between gene and
      environment were fitted under the recessive, dominant, additive and codominant
      mode, respectively. RESULTS: Three models were screened as the optimal models
      under the additive mode and one model under the dominant mode, according to the
      lowest value of Akaike's Information Criteria (AIC). After the control of age and
      gender, it was found that the frequency of ultraviolet exposure was higher in
      cases than in controls with significant difference under all models (P<0.05). For
      the haplotypes composed of the alleles of PD1.2, PD1.5 and PD1.6, there was
      significantly higher frequency of G-T-A haplotype (0.1196 vs 0.0363) and lower
      frequency of A-C-A haplotype (0.4746 vs 0.5399) in cases than that in controls
      (P<0.05) under the additive mode, and the G-T-A haplotype was associated with an
      increased risk for SLE (OR=4.319), while A-C-A haplotype was shown as a
      protective factor for SLE (OR=0.571). Moreover, interaction between A-C-G
      haplotype and ultraviolet exposure, which was related to an increased risk for
      SLE (beta5=1.182, Z=2.2898, P<0.05, OR=3.261), was also found under this mode.
      Additionally, the frequency of G-C-G haplotype was higher in cases than that in
      controls (0.1287 vs 0.0361) under the dominant mode with statistically
      significant difference (P<0.05, OR=4.332). CONCLUSION: Authors' results indicate
      that ultraviolet exposure, G-T-A or G-C-G haplotype and interaction between A-C-G
      and ultraviolet exposure may be associated with genetic susceptibility to SLE in
      Han population in the southern region of yangtze river in China under certain
      genetic modes.

PMID- 20677150
TI  - [Study on the longevity related mitochondrial genome variation in Bama elderly
      population in Guangxi province].
AB  - OBJECTIVE: To investigate the human mitochondrial DNA (mtDNA) variations
      associated with longevity in Bama elderly population from Guangxi. METHODS:
      Mitochondrial genome of 20 individuals over 96 years of age was sequenced, and
      seven target single nucleotide polymorphism (SNPs) were observed by comparing
      with the standard rCRS sequence, and two were tested by polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) method in a larger population
      including 208 individuals of 90-113 years old, and 586 unrelated control
      individuals from Guangxi. RESULTS: The 4824G frequency of the mtDNA4824A/G locus
      increased with age both in the long-lived elderly and in controls. And it was
      significantly higher in controls than that in long-lived population (P<0.05).
      CONCLUSION: The mtDNA4824 A/G is not only an age-related locus, its mutation is
      also negatively correlated with longevity.

PMID- 20677151
TI  - [Association of polymorphisms of cytochrome P450 2C9 exon 4 and -65G>C with
      warfarin sensitivity].
AB  - OBJECTIVE: To investigate the association of the polymorphisms of cytochrome P450
      2C9 (CYP2C9) exon 4 608T/G, 561A/C, 537A/C and 527A/C, and -65G/C with warfarin
      sensitivity. METHODS: A total of 102 patients under warfarin anticoagulant
      therapy were selected. During follow-up, warfarin dosage and associated
      Prothrombin Time-International Normalized Ratio (P-INR) values were recorded.
      Simultaneous monitoring of incidence of bleeding and thrombosis adverse effect
      was recommended. Genetic polymorphisms of the above mentioned loci were
      identified by polymerase chain reaction and DNA sequencing. RESULTS: The average
      age of the 102 patients was (62.1+/-10.5) years. The body mass index (BMI) was
      (24.7+/-3.8) kg/m2. Mean daily warfarin requirement was from 1.250 to 5.077
      mg/day when therapeutic PT-INR (1.5-2.5) was maintained. DNA sequencing showed no
      polymorphisms of 608T/G, 561A/C, 537A/C, 527A/C in CYP2C9 exon 4. Warfarin daily
      dosage in CYP2C9 exon 4 -65C carriers was 3.106+/-0.619 mg/d, while it was
      (2.555+/-0.708) mg/d in individuals with wild-type -65G (P=0.020). Receiver
      operating characteristic (ROC) analysis showed that warfarin daily dosage of more
      than 2.5 mg/d can be used to predict the CYP2C9 exon 4 -65GC genotype (AUC:
      0.770, P=0.005, 95%CI:0.626-0.915). Logistic regression indicated that BMI was an
      independent factor of bleeding during anti-coagulation therapy (OR=0.794, 95%CI:
      0.651-0.970, P=0.024). CONCLUSION: The Chinese population are, generally,
      warfarin-sensitive. Exon 4 of the CYP2C9 gene is highly conserved in this
      population. The warfarin maintenance dosage in CYP2C9 exon 4 -65CG carriers was
      significantly higher than those with wild-type -65GG. The clinical significance
      needs further investigation with more large-scale, multi-center trials.

PMID- 20677152
TI  - [Association of transcription factor FOXP3 gene polymorphism with genetic
      susceptibility to systematic lupus erythematosus in Guangxi Zhuang population].
AB  - OBJECTIVE: To investigate the association of single nucleotide polymorphisms(SNP)
      of FOXP3 gene with susceptibility to systematic lupus erythematosus (SLE) in
      Chinese Zhuang population. METHODS: Author analyzed the -2383 C/T and -3281 C/A
      two SNPs of the FOXP3 gene promoter in 120 patients with SLE and 160 age and sex
      matched controls in a Chinese Zhuang population, using polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) strategy and DNA sequencing.
      RESULTS: The distribution of the FOXP3 gene -3281 C/A polymorphism was not
      different between the two groups. However, the FOXP3 gene -2383 C/T polymorphism
      was significantly different (P<0.05) between the two groups. The relative risk of
      suffering from SLE of -2383T allele carriers was 1.715 times of the -2383C allele
      carriers (OR=1.715, 95%CI: 1.165-2.525). Consistent with the results of the
      genotyping analyses, the FOXP3 -2383T/-3281A haplotype frequency in patients with
      SLE was significantly higher than that in controls (P<0.05). The -2383T/-3281A
      allele was associated with a significantly increased risk of SLE (OR=2.196,
      95%CI: 1.165-4.142). CONCLUSION: The FOXP3 gene -2383C/T polymorphism is
      associated with SLE, and the -2383T allele is risk factor for SLE in the
      population studied.

PMID- 20677153
TI  - [Prenatal diagnosis of a fetus in a family with mandibulofacial dysostosis].
AB  - OBJECTIVE: To measure the feasibility of application of comparative genomic
      hybridization technique in the prenatal diagnosis of fetus with mandibulofacial
      dysostosis. METHODS: A pregnant woman having a fetus with mandibulofacial
      dysostosis diagnosed by prenatal ultrasound test was selected. The amniotic fluid
      and blood of the pregnant and blood of her husband were collected and
      conventional cytogenetic analysis was performed. The whole genome was scanned by
      array comparative genomic hybridization assay (array-CGH). Reverse transcription
      fluorescence quantitative PCR (RT-qPCR) analysis was used to verify the result of
      array-CGH. RESULTS: No abnormality was found in conventional cytogenetic analysis
      while a duplicated region in 1p36.33 was detected by array-CGH assay. The region
      spans 722 kb and contains two genes, VWA1 and PYGO2, which play roles in the
      development of cartilage. The result of array-CGH was confirmed by the RT-qPCR
      assay. The diagnosis of mandibulofacial dysostosis was confirmed after birth.
      CONCLUSION: Author diagnosed a fetus with mandibulofacial dysostosis by array-CGH
      assay and found two candidate genes related to the development of craniofacial
      bone: VWA1 and PYGO2.

PMID- 20677154
TI  - [Detection of complex chromosomal aberrations in patients with multiple myeloma
      using multiplex fluorescence in situ hybridization].
AB  - OBJECTIVE: To explore the value of multiplex fluorescence in situ hybridization
      (M-FISH) in the detection of the complex chromosomal aberrations (CCAs) in
      multiple myeloma (MM). METHODS: M-FISH was used in 10 MM patients with CCAs
      detected by conventional cytogenetics (CC) using R-banding to refine the
      rearrangement of CCAs and identify the characteristics of marker chromosome.
      RESULTS: M-FISH confirmed the 29 structural aberrations shown by CC analysis, and
      also confirmed the specific source of 21 types of chromosomal aberration, which
      were not detected by CC analysis. Among them, t(2;15)(q33;q22), t(6;7)(q23;q34),
      t(8;11) (q24;q23), t(1;14)(q10;q32) and t(X;1)(q26;q25) were new chromosomal
      aberrations. The median survival time of 9 MM patients with CCAs was 23 months
      and evidently shorter than that of MM patients without CCAs, with the mean
      survival time being 34 months. CONCLUSION: M-FISH could refine CCAs in MM
      patients, find or correct the missed or misidentified abnormalities analyzed by
      CC. It has provided one of the essential methods for the research of chromosomal
      aberrations in MM.

PMID- 20677156
TI  - [Rapid diagnosis of Down's and Edward's syndrome by multiplex real-time
      quantitative PCR].
AB  - OBJECTIVE: To establish a multiplex real-time quantitative PCR method for
      diagnosis of Down's and Edward's syndrome. METHODS: The sequences of the amyloid
      precursor protein gene (APP) in the Down's region of chromosome 21 and the
      thymidylate synthetase gene (TYMS) on chromosome 18 were co-amplified in the same
      tube. The relative quantitative index DeltaCT value was used to differentiate
      Down's and Edward's syndrome patient from healthy individual. Four groups of
      samples, including 36 blood samples from normal controls (group A), 15 amniotic
      fluid samples from normal pregnancies (group B), 21 samples from patients with
      Down's syndrome (group C) and 6 samples from patients with Edward's syndrome
      (group D), were investigated in the study. RESULTS: The mean DeltaCT values of
      the four groups were -0.48+/-0.15, -0.49+/-0.12, -1.26+/-0.17 and 0.25+/-0.12
      respectively. The DeltaCT value from group B was not different from that from
      group A (P>0.05). However, the DeltaCT values from group C and group D were
      significantly different from that from group A (P<0.01), and no overlapping was
      observed. CONCLUSION: The DeltaCT values from multiplex real-time quantitative
      PCR could be used to rapidly diagnose Down's and Edward's syndrome
      simultaneously.

PMID- 20677155
TI  - [Association of FGFR2 gene polymorphism with estrogen receptor positive breast
      cancer detected by fluorescent quantitative PCR].
AB  - OBJECTIVE: To investigate the association of fibroblast growth factor receptor 2
      gene (FGFR2) rs2981582 polymorphism with breast cancer in Chinese women. METHODS:
      A case-control study was performed in 936 breast cancer patients and 471 patients
      with benign breast diseases by using a novel fluorescent quantitative PCR method.
      RESULTS: The numbers and frequencies of genotypes CC, CT, and TT in the control
      group were 234(49.68%), 181(38.43%) and 56(11.89%) respectively. The numbers and
      frequencies of genotypes CC, CT, and TT in the breast cancer group were
      426(44.56%), 400(41.84%) and 130(13.60%) respectively. And no significant
      difference was found between the two groups (P=0.183). However, stratified
      analysis found that the numbers and frequencies of genotypes CC, CT, TT in the
      estrogen receptor(ER) positive subgroup of breast cancer patients were
      189(41.27%), 202(46.12%) and 67(14.63%) respectively, and significant difference
      was observed compared with control group (P=0.035). CONCLUSION: Association was
      found in the single nucleotide polymorphism(SNP) of the rs2981582 locus of intron
      2 in FGFR2 gene between the ER positive breast cancer patients and control
      patients with benign breast diseases. The fluorescent quantitative PCR is a
      specific, easy-to-operate, low-expense method and is suitable for SNP detection
      in large scale samples.

PMID- 20677157
TI  - [Application of fluorescence in situ hybridization to prenatal diagnosis of
      aneuploidy in 110 uncultured amniotic fluid samples].
AB  - OBJECTIVE: To optimize the prenatal diagnosis platform by using domestically made
      fluorescence in situ hybridization(FISH) kit and to explore the clinical
      application of FISH to rapid prenatal diagnosis of a wide range of chromosomal
      abnormalities. METHODS: Amniotic fluid samples from 110 pregnant women were
      studied with the rapid prenatal diagnosis method of FISH and the conventional
      cell culture method of karyotyping, the results from both methods were compared.
      RESULTS: Four cases of trisomy 21, 1 case of trisomy 18, 58 cases of 46, XX, and
      47 cases of 46, XY were detected by FISH in the 110 amniotic fluid samples. It is
      concordant with the results from conventional karyotype analysis. The concordance
      rate is 100%. CONCLUSION: Domestically made FISH kit can be used to rapidly and
      accurately detect the most common chromosome aneuploidies by using less sample
      volume while the price is relatively low. FISH can be a reliable and rapid
      prenatal diagnostic tool as an adjunct to classical cytogenetic study. It can be
      used for rapid and accurate prenatal diagnosis of women with high risk of
      maternal serum screening.

PMID- 20677158
TI  - [No association of vascular endothelial growth factor A gene rs9369425
      polymorphism with glucose metabolism in Chinese Han population].
AB  - OBJECTIVE: To investigate the relationship between the vascular endothelial
      growth factor A gene (VEGFA) rs9369425 single nucleotide polymorphism (SNP) and
      type 2 diabetes in Chinese Han population. METHODS: One thousand eight hundred
      and ninety two type 2 diabetes patients and 1808 controls with normal glucose
      were recruited in this study. Phenotypes including body mass index, waist, waist
      hip ratio, plasma glucose and serum insulin levels of blood obtained both at 0
      and 120 minute during standard 75-gram glucose oral glucose tolerance tests, were
      analyzed. Insulin resistance and beta cell function were assessed by homeostasis
      model assessment (HOMA-IR and HOMA-B). Genotyping was performed by time-of-light
      mass spectrum using a Sequenom platform. RESULTS: The frequencies of minor allele
      G in the diabetic patients and controls were 10.8% and 11.3% respectively. No
      significant difference of allele distribution was detected between the cases and
      controls (P=0.5086). No significant difference (P>0.05) was detected on the
      association between rs9369425 SNP and clinical phenotypes. CONCLUSION: VEGFA
      rs9369425 was not associated with type 2 diabetes in Chinese Han population.
      Whether there is association in any other loci in this gene remained to be
      investigated.

PMID- 20677159
TI  - [Chromosome abnormalities and Y chromosome microdeletions in patients with the
      azoospermia and cryptozoospermia].
AB  - OBJECTIVE: To study the incidence of the chromosome abnormalities and Y
      chromosome microdeletions in Chinese patients with azoospermia and
      cryptozoospermia. METHODS: Conventional chromosomal karyotyping was used to
      analyze the chromosome abnormalities. Genomic DNA was extracted from peripheral
      blood samples and multiplex polymerase chain reactions (PCR) analyses were
      performed using specific primers to confirm the presence or absence of Y
      chromosome microdeletions. A total of 997 patients with azoospermia and
      cryptozoospermia were enrolled in the study. RESULTS: The incidence of chromosome
      abnormalities in the patient with azoospermia and cryptozoospermia was 28.4%. The
      major abnormal karyotypes included 47,XXY, 46,XY (Y>G), 46,XX, chimera and
      translocations. The incidence of the Y chromosome microdeletions was 17.4%. They
      were mainly found in the karyotypes of 46,XY and 46,XY (Y>G). CONCLUSION:
      Chromosome abnormalities were the most common hereditary causes of the patients
      with azoospermia and cryptozoospermia. The incidence of Y chromosome
      microdeletion was higher in the patients with karyotype of 46,XY and 46,XY (Y>G).
      Therefore, detection of the AZF microdeletion in these patients is helpful to
      determine the etiology and avoid the unnecessary treatment and vertical
      transmission of the genetic defects.

PMID- 20677160
TI  - [Association of the TGF-beta1 gene polymorphisms and blood TGF-beta 1 level with
      essential hypertension in Kazakh Chinese].
AB  - OBJECTIVE: To investigate the association of the transforming growth factor- beta
      1 (TGF- beta 1) gene polymorphisms and blood TGF- beta 1 level with essential
      hypertension (EH) in Kazakh Chinese. METHODS: The polymorphisms of TGF- beta 1
      gene in 354 Kazakh EH patients and 435 healthy controls were detected with
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and
      DNA sequencing. The blood level of TGF- beta 1 was quantified using specific
      sandwich ELISA. RESULTS: The frequencies of genotypes GG, GC and alleles G and C
      of +915G/C in Xinjiang Kazakh were 97.9%, 2.1% and 98.77%, 1.23%, respectively.
      No significantly difference was found between EH patients and controls (P>0.05).
      The frequencies of genotypes TT, TC, CC and alleles T and C of +869T/C in
      controls was 25.97%, 46.67%, 27.36%, 49.3% and 50.7%, respectively, the CC
      genotype or C allele in EH patients had significantly higher frequencies than
      controls [41.60% vs. 27.36%, and 62.2% vs. 50.7%, respectively (P<0.05)]. It was
      also shown that TGF- beta 1 +869 C allele carriers had significantly increased
      risk of EH compared with T allele carriers (OR=1.60, P=0.00). There was linkage
      disequilibrium (LD) between the two polymorphisms. The frequency of haplotype C-G
      in the EH group was significantly higher than that in controls (61.6% vs. 49.8%,
      P<0.05). There were no differences in TGF- beta 1 level among different genotypes
      or alleles in both +869T/C and +915G/C loci (P>0.05). CONCLUSION: The frequency
      of +915G/C variation of the TGF- beta 1 gene was very low in Kazakh and there was
      no homozygous variation. The +869 C allele was likely the genetic susceptibility
      factor for EH in the population. There was linkage disequilibrium in the
      polymorphisms of +869T/C and +915G/C. Haplotype C-G was the risk factor of EH.

PMID- 20677161
TI  - [Molecular genetic analysis of a new B112 allele of ABO blood group].
AB  - OBJECTIVE: To analyze the molecular genetic basis for a new B112 allele of ABO
      blood group and the pedigree of the proband. METHODS: The ABO group antigens on
      red cells of the proband were identified by monoclonal antibodies. The ABO
      antibody in serum was detected by using standard A, B and O cells. The exons 5-7
      of ABO gene for the proband was amplified by polymerase chain reaction and the
      amplified products were digested with double enzymes and sequenced for exons 6
      and 7. A magnetic bead-based, haplotype specific extraction was used to separate
      the diploid sample of the proband into its haploid components. The exons 6 and 7
      of the two single ABO haplotypes were then amplified and sequenced separately.
      The samples of the parents of the proband were collected, and the blood group
      serological test and sequence analysis for exons 6 and 7 of ABO gene were
      performed. RESULTS: The serum characteristic of the proband was consisted with
      the normal B phenotype. The DNA sequencing of exons 6 and 7 showed 261G/del,
      297A/G, 526C/G, 559C/T, 657C/T, 703G/A, 796C/A, 803G/C and 930G/A heterozygotes
      and was assigned for B/O genotype. After separation of the two single strands of
      the proband with haplotype specific extraction, a B112 and an O01 allele were
      identified after sequencing. The B112 allele had one nucleotide change (C to T)
      at position 559 compared with B101, which resulted in an amino acid change at
      position 187 (Arg to Cys). The B112 in the proband was identified to inherit from
      his mother after pedigree analysis, the ABO blood group serological
      characteristics and sequences of exons 6 and 7 of the mother were identical to
      that of the proband. CONCLUSION: A novel B112 allele of ABO group system with
      559C>T was identified. It had normal B antigen expression, suggesting that
      Arg118Cys of alpha-1, 3 galactosyltransferase did not affect its enzyme activity.

PMID- 20677162
TI  - [The genetic diversity in the full coding region of human FUT5 gene in a Chinese
      Han population].
AB  - OBJECTIVE: To reveal the sequence variations of the full coding region of the
      human alpha (1,beta/1,4) fucosyltransferase 5 gene (FUT5) in a Chinese Han
      population. METHODS: The whole coding region of the FUT5 gene was amplified and
      sequenced in a total of 30 unrelated Chinese Han individuals. The PCR products
      containing the nucleotide variants observed in the study were subcloned into
      plasmid pcDNA to determine all potential haplotypes in the investigated
      population. Genetic polymorphisms of C560T (rs778970) and C484A loci were further
      analyzed by polymerase chain reaction-restriction fragment length
      polymorphism(PCR-RLFP) method. RESULTS: In addition to seven previously reported
      base substitutions, two novel polymorphisms, namely C484A (Leu162Met) and T684C,
      were found in the coding region of the FUT5 gene in the 30 individuals. Seven
      haplotypes were identified by subcloning the variants into plasmid and subsequent
      DNA sequencing. The allele frequencies in the rs778970 locus in 160 Chinese Han
      individuals was 0.3031 for 560C and 0.6969 for 560T, while no polymorphism was
      detected in the C484A locus. CONCLUSION: The sequence of the coding region in the
      human FUT5 gene demonstrated high genetic diversity, and the allelic distribution
      of the rs778970 locus in the Chinese populations is polymorphic.

PMID- 20677164
TI  - Diuretic therapy: key aspects in hypertension and renal disease.
AB  - Diuretics are a heterogeneous class of drugs of tremendous importance in both the
      prevention and treatment of cardiovascular and renal disease. Used as
      antihypertensives, diuretic-based therapy to lower blood pressure reduces
      cardiovascular events. In addition to their role as preventive agents, diuretics
      are critical to the management of several commonly encountered edematous
      conditions, including chronic kidney disease and the nephrotic syndrome. Because
      a threshold amount of diuretic is necessary to elicit the intended natriuretic
      effect, alterations in the pharmacokinetic and pharmacodynamic parameters
      occurring in the presence of a variety of renal conditions necessitate careful
      dose titrations and adjustment. Higher doses or more frequent administration may
      be necessary to maintain the drug level above the diuretic threshold. In
      refractory cases, diuretics with differing sites of action in the nephron can be
      combined to potentiate therapeutic effects. Selection of the proper diuretic
      agent and its dosing strategy are dependent on knowledge of within-class
      characteristics, as well as a commensurate understanding of the physiology of the
      disease being treated.

PMID- 20677165
TI  - IGF-II mRNA expression in breast cancer: predictive value and relationship to
      other prognostic factors.
AB  - PURPOSE: Insulin-like growth factor-II (IGF-II) is an important regulator of
      tumor growth in breast cancer. In this study we have examined the prognostic
      value of IGF-II mRNA expression in breast cancer and its relationship to other
      predictive parameters. PATIENTS: Sixty-eight women with infiltrating ductal
      carcinoma were given the same treatments including mastectomy and antitumoral
      therapies and followed up for 5 years. RESULTS: The overall 5-year survival rate
      was 73.5% (55/68). IGF-II mRNA was expressed in 33/64 patients (51.6%) and had no
      significant impact on survival. The expression of estrogen receptor (ER) and
      progesterone receptor (PgR) did not significantly affect the 5-year survival, but
      in the presence of an IGF-II mRNA signal, the survival of ER- and PgR-negative
      patients (n=9) was lower than that of ER- and PgR-positive patients (n=15),
      although the difference was not significant. The 5-year survival was not
      significantly different between Ki-67-positive and negative patients, but in the
      IGF-II positive group Ki-67-positive patients (n=7) had a significantly poorer
      prognosis than Ki-67-negative patients (n=26). The expression of p53 protein was
      associated with a poorer prognosis: 6/11 (54.5%) p53-positive patients died in
      the first 26 months of follow-up and 5 of these 6 patients (83.3%) also had
      positive IGF-II mRNA expression. CONCLUSIONS: IGF-II mRNA expression per se is
      not an independent predictive factor in breast cancer but may be a marker of poor
      prognosis when associated with other prognostic factors such as Ki-67 index and
      p53 expression.

PMID- 20677166
TI  - Downregulation of AP-1 repressor JDP2 is associated with tumor metastasis and
      poor prognosis in patients with pancreatic carcinoma.
AB  - Pancreatic carcinoma is one of the most malignant and aggressive cancers. The
      identification of prognostic factors is thought to be useful in directing
      treatment. Transcription factor Jun dimerization protein 2 (JDP2), a member of
      the activator protein 1 (AP-1) family, acts as an AP-1 inhibitor and has been
      implicated in many cellular processes including carcinogenesis. The role of JDP2
      in the development of pancreatic carcinoma, however, remained elusive. In this
      study we examined the expression levels of JDP2 in 36 pancreatic carcinoma
      samples by Western blotting and found that JDP2 expression was significantly
      downregulated in pancreatic carcinoma samples compared with peritumoral tissues.
      The decrease in JDP2 expression was correlated with lymph node metastasis and
      distant metastasis and strongly associated with the post-surgery survival time.
      These results indicate a possible connection between JDP2 expression and
      metastasis in pancreatic carcinoma and suggest that JDP2 can serve as a biomarker
      to predict the prognosis of patients with this cancer.

PMID- 20677167
TI  - Alagille syndrome: clinical and ocular pathognomonic features.
AB  - PURPOSE: This study was carried out to determine the frequency of clinical
      diagnostic criteria in patients with Alagille syndrome (AGS) in comparison to a
      group of children with cholestasis and histologically proven neonatal hepatitis
      (NH). The type and frequency of ocular manifestations are highlighted. METHODS:
      According to histologic findings on liver biopsy, the 32 patients included in the
      study were classified into 2 groups: group 1 had paucity of interlobular bile
      ducts (PILBD) (n=13) and at least 3 of 5 characteristics of AGS and group 2 had
      NH on liver biopsy (n=19). RESULTS: The mean age of patients with AGS was higher
      than in group 2 (3.9 vs 1.6 years) (p<0.05). Pruritus was a significant symptom
      in the AGS group (p<0.05). Characteristic facies was detected in 61.5% of the AGS
      group. None of our patients with AGS had vertebral anomalies. Although cardiac
      murmurs were heard in 5 patients with AGS, cardiac anomalies were detected in
      only 3 by echocardiography: pulmonary stenosis in 2 patients and patent foramen
      ovale in 1. Posterior embryotoxon (PE) was detected in 69.2% of patients with AGS
      as compared to 10.5% of the NH group. Optic nerve drusen was detected in 91% of
      patients with AGS as compared to 5.3% of patients with NH. CONCLUSIONS: Optic
      nerve drusen was the most common finding in AGS, followed by PE and facial
      features. Ocular ultrasound needs to be performed in all cholestatic infants with
      PILBD.

PMID- 20677168
TI  - Pulmonary edema following instillation of topical phenylephrine eyedrops in a
      child under general anesthesia.
AB  - PURPOSE: To report a case of pulmonary edema, in a child under general
      anesthesia, due to iatrogenic acute hypertensive crisis following instillation of
      1 drop of 5% phenylephrine eyedrops. METHODS: A 2-year-old boy was scheduled for
      examination of both eyes and enucleation of the left eye under general
      anesthesia. In the preoperative ward, 1 drop of 2.5% phenylephrine eyedrops was
      instilled 3 times by the nursing staff. The child was induced with the volatile
      agent Sevoflurane and intubated with Inj atracurium besylate 0.5 mg/kg IV.
      Anesthesia was maintained with N2O/oxygen (2:1)/Sevoflurane 1.5% and Inj fentanyl
      1 ug/kg IV. As the pupil was not dilated optimally for examination, 1 drop of 5%
      phenylephrine eyedrops was instilled. Approximately 10 minutes following its
      instillation, tachycardia and rise in blood pressure occurred. Auscultation of
      the chest revealed bilateral coarse crepitations and pink frothy secretions were
      noted in the Portex endotracheal tube. RESULTS: Pulmonary edema was effectively
      settled using positive pressure ventilation with 100% oxygen, Inj lasix 1 mg/kg
      IV, and Inj hydrocortisone 100 mg IV. The concentration of inhalational agent,
      Sevoflurane, was increased. Within about 15 minutes, both heart rate and blood
      pressure gradually returned to normal limits. Following surgery, the child was
      extubated, fully awake. CONCLUSIONS: To produce maximum mydriasis, with minimum
      systemic effects, preventive strategies such as using the lowest drug
      concentration, punctual occlusion, eyelid closure, allowing adequate time for the
      pharmacologic effect to occur, and the use of microdrops in infants should be
      adopted.

PMID- 20677170
TI  - The challenge of evaluating mental health services for older people.
AB  - BACKGROUND: Despite a consensus on the need to expand and improve mental health
      care for older people, evidence on models of service development is limited.
      OBJECTIVE: Referring to two case studies, this paper considers how evaluation of
      service innovations can inform policy and practice. CONCLUSIONS: Evaluation
      should entail a dual concern with measurement and meaning in judging the value of
      an intervention.

PMID- 20677171
TI  - Living arrangements, social networks and depressive symptoms among older men and
      women in Singapore.
AB  - OBJECTIVES: To examine the association of living arrangements and social networks
      outside the household with depressive symptoms among older men and women,
      ascertain if these relationships differ between older men and women, and
      investigate whether the association of living arrangements with depressive
      symptoms varies by strength of social networks. METHODS: Data for 4489 community
      dwelling Singaporeans, aged 60 years and older, from a recent nationally
      representative survey were analyzed. Depressive symptoms were assessed using the
      11-item CES-D (Center for Epidemiologic Studies) scale, social networks through
      Lubben's revised social network scale, and living arrangements through household
      composition. Analysis was stratified by gender, and descriptive and multivariate
      statistics were used to assess the risk of depressive symptoms by living
      arrangements and social networks, adjusting for age, ethnic group, education,
      housing type, functional status, number of chronic diseases and involvement in
      social activities. RESULTS: Women had higher depressive symptom scores than men.
      Living alone and living with at least 1 child (no spouse) (relative to living
      with spouse and children), and weak social networks outside the household were
      associated with higher depressive symptom scores among both men and women. Men
      living alone with weak social networks outside the household had higher
      depressive symptom scores than those with strong networks. CONCLUSION: The
      findings have implications regarding the importance of strengthening non-familial
      social networks of older adults, particularly for those living alone.

PMID- 20677172
TI  - The interaction between cerebrovascular disease and neuroticism in late-life
      depression: a cross-sectional study.
AB  - OBJECTIVE: Vascular disease and neuroticism are both risk factors for late-life
      depression. In this study we examined the interaction between vascular disease
      and neuroticism as determinants of clinically relevant depressive symptoms (CRDS)
      in late-life. METHODS: Multivariate logistic regression in a survey of 1396
      population-dwelling people aged >=70 years. CRDS were defined as scoring >=16 on
      the CES-D. Vascular disease was categorised into four levels: none, >=2 vascular
      risk factors, cardiac disease or stroke. RESULTS: Neuroticism was strongly
      associated with CRDS in women (OR: 1.6, 95% CI: 1.4-1.8). In men vascular disease
      interacted negatively but significantly with neuroticism (cardiac disease by
      neuroticism: OR: 0.8, 95% CI: 0.6-0.9; stroke by neuroticism: OR: 0.8, 95% CI:
      0.6-0.96) when predicting CRDS. CONCLUSIONS: In men vascular disease attenuates
      the predictive value of neuroticism in CRDS, which might be mediated by apathy
      caused by cerebrovascular disease.

PMID- 20677173
TI  - Relevance of a scoring system including CD11c expression in the identification of
      splenic diffuse red pulp small B-cell lymphoma (SRPL).
AB  - 'Splenic red pulp lymphoma with numerous basophilic villous lymphocytes' (SRPL),
      recently described, is characterized by clinical, morphologic, immunologic,
      cytogenetic and molecular features distinct from SMZL/SLVL and HCL. In
      particular, the intensity of CD11c staining (expressed as fluorescence intensity 
      RFI-) in SRPL is significantly different from the RFI in SMZL/SLVL and HCL.
      Moreover the use of a scoring system based on the expression of CD11c, CD22,
      CD76, CD38 and CD27 appears to improve the differential diagnosis between SRPL
      and SMZL/SLVL and emphasizes that SRPL is an entity closed to but distinct from
      SMZL/SLVL.

PMID- 20677174
TI  - SVM based prediction of RNA-binding proteins using binding residues and
      evolutionary information.
AB  - RNA-binding proteins (RBPs) play crucial role in transcription and gene
      regulation. This paper describes a support vector machine (SVM) based method for
      discriminating and classifying RNA-binding and non-binding proteins using
      sequence features. With the threshold of 30% interacting residues, RNA-binding
      amino acid prediction method PPRINT achieved the Matthews correlation coefficient
      (MCC) of 0.32. BLAST and PSI-BLAST identified RBPs with the coverage of 32.63 and
      33.16%, respectively, at the e-value of 1e-4. The SVM models developed with amino
      acid, dipeptide and four-part amino acid compositions showed the MCC of 0.60,
      0.46, and 0.53, respectively. This is the first study in which evolutionary
      information in form of position specific scoring matrix (PSSM) profile has been
      successfully used for predicting RBPs. We achieved the maximum MCC of 0.62 using
      SVM model based on PSSM called PSSM-400. Finally, we developed different hybrid
      approaches and achieved maximum MCC of 0.66. We also developed a method for
      predicting three subclasses of RNA binding proteins (e.g., rRNA, tRNA, mRNA
      binding proteins). The performance of the method was also evaluated on an
      independent dataset of 69 RBPs and 100 non-RBPs (NBPs). An additional
      benchmarking was also performed using gene ontology (GO) based annotation. Based
      on the hybrid approach a web-server RNApred has been developed for predicting RNA
      binding proteins from amino acid sequences
      (http://www.imtech.res.in/raghava/rnapred/).

PMID- 20677175
TI  - Forsythoside a inhibits the avian infectious bronchitis virus in cell culture.
AB  - Forsythoside A is a polyphenolic constituent of the fruits of Forsythia suspensa
      Vahl. which is widely used as an antiinflammatory agent in traditional Chinese
      medicine. In the present study, the effects of forsythoside A on cell infection
      by avian infectious bronchitis virus were assessed. A real-time fluorescence
      quantitative PCR assay was used to determine mRNA content of IBV N gene. The
      pretreatment of cells with forsythoside A, adding forsythoside A post infection
      of cells, and treatment of virus with forsythoside A were analysed. The
      inhibitory effect of forsythoside A was confirmed by infecting primary chicken
      embryo kidney cells. Infected cells were inhibited by forsythoside A treatment.
      The data indicated that forsythoside A has the potential to prevent IBV infection
      in vitro. Copyright (c) 2010 John Wiley & Sons, Ltd.

PMID- 20677176
TI  - In vitro anticariogenic effects of aerial parts of Potentilla recta and its
      phytochemical profile.
AB  - This study, for the first time, investigated the in vitro inhibitory effects of
      Potentilla recta extracts and subfractions obtained with solvents of different
      polarity (aqueous, 50% ethanol, diethyl ether, ethyl acetate and n-butanol)
      against cariogenic Streptococcus spp. strains. It was found that the tested
      samples inhibited the growth of oral streptococci. Furthermore, all five P. recta
      preparations exhibited an inhibitory effect on water-insoluble alpha-(1->3)
      ,alpha-(1->6)-linked glucan (mutan) and artificial dental plaque formation. The
      ethyl acetate fraction showed the highest antibiofilm activities especially
      against S. sobrinus GCM 20381, with minimum mutan and biofilm inhibition
      concentrations of 6.25 and 25 ug/mL, respectively. The phytochemical profile of
      active constituents in the investigated samples was analysed. The high
      polyphenolics (total phenol, phenolic acids, tannins, proantocyanidins,
      flavonoids) content were found. The ethyl acetate fraction showed the highest
      concentration of total polyphenol content which may correlate with the high
      cariogenic activity of this subfraction. The results demonstrate that P. recta
      extracts and subfractions could become useful supplements for pharmaceutical
      products as new anticariogenic agents in a wide range of oral care products.
      Further studies are necessary to clarify the precise bioactive constituents of P.
      recta responsible for the anticariogenic properties.

PMID- 20677177
TI  - A comparative study of activity and apparent inhibition of fungal beta
      glucosidases.
AB  - beta-Glucosidases (BGs) from Aspergillus fumigates, Aspergillus niger,
      Aspergillus oryzae, Chaetomium globosum, Emericella nidulans, Magnaporthe grisea,
      Neurospora crassa, and Penicillium brasilianum were purified to homogeneity, and
      analyzed by isothermal titration calorimetry with respect to their hydrolytic
      activity and its sensitivity to glucose (product) using cellobiose as substrate.
      Global non-linear regression of several reactions, with or without added glucose,
      to a product inhibition equation enabled the concurrent derivation of the kinetic
      parameters k(cat), K(m), and the apparent product inhibition constant (app)K(i)
      for each of the enzymes. A more simple fit is not advisable to use as the
      determined (app)K(i) are in the same range as their K(m) for some of the tested
      BGs and produced glucose would in these cases interfere. The highest value for
      k(cat) was determined for A. fumigatus (768 s(-1)) and the lowest was a factor 9
      less. K(m) varied by a factor of 3 with the lowest value determined for C.
      globosum (0.95 mM). The measured (app)K(i) varied a factor of 15; the hydrolytic
      activity of N. crassa being the most resistant to glucose with an apparent
      product inhibition constant of 10.1 mM. Determination of (app)K(i) using
      cellobiose as substrate is important as it reflects to what extent the different
      BGs are hydrolytically active under industrial conditions where natural
      substrates are hydrolyzed and the final glucose concentrations are high.

PMID- 20677178
TI  - Immunomodulation property of hexane fraction of leaves of Cinnamomum tamala Linn.
      in rats.
AB  - The leaves of Cinnamomum tamala Linn. (CT) (Lauraceae) clinically used in
      Ayurveda as antidiabetic and diuretic, but no reports are available towards
      immunomodulating property. Its hexane fraction (CTH) was orally given to rats for
      10 days and delayed type of hypersensitivity (DTH), antibody production against
      sheep red blood cells (SRBCs), mitotic index in bone marrow cells and
      concanavalin A (Con A) mediated proliferation of lymphocytes were assessed.
      Further on 30 days treatment, change in body weight (BW), spleen weight, thymus
      weight, bone marrow cellularity and hematological changes were observed. It
      inhibited significantly the DTH response (IC(50) 1475 +/- 57.19 mg kg(-1) BW),
      antibody production, suppressed mitotic index in bone marrow cells along with the
      suppression of lymphocyte proliferation against Con A (IC(50) 63.33 +/- 1.95
      microg mL(-1)). In all experiments, cyclophasphamide and dexamethasone had been
      used as reference drug for in vivo and in vitro studies, respectively. On 30 days
      treatment, the CTH (800 mg kg(-1) BW and above) significantly suppressed growth
      rate, increase of spleen and thymus weight and low bone marrow cellularity. In
      hematological examination, it inhibited total white blood cell and lymphocytes
      count and increased per cent of polymorphs. Thus, it could be suggested that the
      fraction possesses immunosuppressive property at doses, higher than 800 mg kg(-1)
      BW in rats.

PMID- 20677180
TI  - Cytotoxic effects induced by unmodified and organically modified nanoclays in the
      human hepatic HepG2 cell line.
AB  - The term 'nanoclay' generically refers to the natural clay mineral,
      montmorillonite, with silica and alumina as the dominant constituents. The
      incorporation of nanoclays into polymeric systems dramatically enhances their
      barrier properties as well as their thermal and mechanical resistance.
      Consequently, nanoclays are employed in a wide range of industrial applications
      with recent studies reporting potential use in the modulation of drug release.
      With the increase in manufacturing of nanoclay-containing products, information
      on the toxicological and health effects of nanoclay exposure is warranted. Thus,
      the objective of the present study was to evaluate the cytotoxicity of two
      different nanoclays: the unmodified nanoclay, Cloisite Na+ (r), and the
      organically modified nanoclay, Cloisite 93A(r), in human hepatoma HepG2 cells.
      Following 24 h exposure the nanoclays significantly decreased cell viability.
      Cloisite Na+ induced intracellular reactive oxygen species (ROS) formation which
      coincided with increased cell membrane damage, whilst ROS generation did not play
      a role in Cloisite 93A-induced cell death. Neither of the nanoclays induced
      caspase-3/7 activation. Moreover, in the cell culture medium the nanoclays
      aggregated differently and this appeared to have an effect on their mechanisms of
      toxicity. Taken together, our data demonstrate that nanoclays are highly
      cytotoxic and as a result pose a possible risk to human health.

PMID- 20677179
TI  - Facilitating online support groups for cancer patients: the learning experience
      of psycho-oncology clinicians.
AB  - OBJECTIVE: Counsellor familiarity and engagement with technology-mediated
      communication represents an important factor in the ability to implement support
      programs to cancer patients. This study describes the experiences of a cohort of
      expert psycho-oncology counsellors who learned to facilitate online support
      groups (OSGs) and identifies the important elements of their learning experience
      that led to their engagement. PROCEDURE AND METHOD: Six psycho-oncology
      counsellors were trained to facilitate OSGs and later facilitated OSGs in their
      own practice context. They subsequently reflected on and discussed their
      experiences with OSGs over time: in a panel discussion within 6 months of
      training, and in two focus groups. A participatory method was used to describe
      and interpret key elements of the learning process. RESULTS AND DISCUSSION: Three
      themes of the counsellors' learning experience emerged: immersion in experiential
      learning, perceptions of clinical value and benefit, and overcoming challenges
      with adapted skills. Counsellors described components of their experiential
      learning: co-facilitating online cancer support groups with an expert, debriefing
      online, and participating in an online peer supervision group, as critical to
      their becoming engaged. Despite initial challenges, the counsellors learned new
      skills, and adapted known clinical skills, to the text-only environment.
      CONCLUSION: With appropriate training and practice over time, counsellors
      familiar with delivering face-to-face support groups to cancer patients became
      skilled and engaged in leading OSG's for cancer patients. Learning to facilitate
      OSGs shifted practice by significantly expanding the scope of services they were
      able to provide their patients and has implications for expanding access to
      support services.

PMID- 20677181
TI  - Two step capture and purification of IgG2 using multicolumn countercurrent
      solvent gradient purification (MCSGP).
AB  - A two-step chromatography process for monoclonal antibody (mAb) purification from
      clarified cell culture supernatant (cCCS) was developed using cation exchange
      Multicolumn Countercurrent Solvent Gradient Purification (MCSGP) as a capture
      step. After an initial characterization of the cell culture supernatant the
      capture step was designed from a batch gradient elution chromatogram. A variety
      of chromatographic materials was screened for polishing of the MCSGP-captured
      material in batch mode. Using multi-modal anion exchange in bind-elute mode, mAb
      was produced consistently within the purity specification. The benchmark was a
      state-of-the-art 3-step chromatographic process based on protein A, anion and
      cation exchange stationary phases. The performance of the developed 2-step
      process was compared to this process in terms of purity, yield, productivity and
      buffer consumption. Finally, the potential of the MCSGP process was investigated
      by comparing its performance to that of a classical batch process that used the
      same stationary phase.

PMID- 20677182
TI  - New life for schizophrenia psychotherapy in the light of phenomenology.
AB  - Recent contributions to the theoretical conception and empirical evaluation of
      schizophrenia in the light of phenomenology are opening the way to new
      perspectives in psychotherapy. The phenomenological conception understands
      schizophrenia as a disturbance of the basic sense of selfhood (ipseity)
      characterized by hyper-reflexivity and diminished sense of self. Evaluation
      consists of examining the anomalous self-experience in a series of domains, which
      makes the conception presented operable. On this basis, a phenomenologically
      informed psychotherapy is introduced. Its characteristics are pointed out and
      early intervention is reviewed (the last frontier in psychosis) from this
      perspective. Finally, a series of psychotherapies which, although they do not
      have a phenomenological origin, may be seen from that perspective, are re
      examined. These are the narrative, mindfulness and acceptance and commitment
      therapies.

PMID- 20677183
TI  - Toxicological aspects of long-term treatment of keratinocytes with ZnO and TiO2
      nanoparticles.
AB  - Sunscreens containing ZnO and TiO(2) nanoparticles (NPs) are increasingly applied
      to skin over long time periods to reduce the risk of skin cancer. However, long
      term toxicological studies of NPs are very sparse. The in vitro toxicity of ZnO
      and TiO(2) NPs on keratinocytes over short- and long-term applications is
      reported. The effects studied are intracellular formation of radicals,
      alterations in cell morphology, mitochondrial activity, and cell-cycle
      distribution. Cellular response depends on the type of NP, concentration, and
      exposure time. ZnO NPs have more pronounced adverse effects on keratinocytes than
      TiO(2). TiO(2) has no effect on cell viability up to 100 MUg mL(-1), whereas ZnO
      reduces viability above 15 MUg mL(-1) after short-term exposure. Prolonged
      exposure to ZnO NPs at 10 MUg mL(-1) results in decreased mitochondrial activity,
      loss of normal cell morphology, and disturbances in cell-cycle distribution. From
      this point of view TiO(2) has no harmful effect. More nanotubular intercellular
      structures are observed in keratinocytes exposed to either type of NP than in
      untreated cells. This observation may indicate cellular transformation from
      normal to tumor cells due to NP treatment. Transmission electron microscopy
      images show NPs in vesicles within the cell cytoplasm, particularly in early and
      late endosomes and amphisomes. Contrary to insoluble TiO(2), partially soluble
      ZnO stimulates generation of reactive oxygen species to swamp the cell redox
      defense system thus initiating the death processes, seen also in cell-cycle
      distribution and fluorescence imaging. Long-term exposure to NPs has adverse
      effects on human keratinocytes in vitro, which indicates a potential health risk.

PMID- 20677184
TI  - Micro- and nanopatterning of functional organic monolayers on oxide-free silicon
      by laser-induced photothermal desorption.
AB  - The photothermal laser patterning of functional organic monolayers, prepared on
      oxide-free hydrogen-terminated silicon, and subsequent backfilling of the laser
      written lines with a second organic monolayer that differs in its terminal
      functionality, is described. Since the thermal monolayer decomposition process is
      highly nonlinear in the applied laser power density, subwavelength patterning of
      the organic monolayers is feasible. After photothermal laser patterning of
      hexadecenyl monolayers, the lines freed up by the laser are backfilled with
      functional acid fluoride monolayers. Coupling of cysteamine to the acid fluoride
      groups and subsequent attachment of Au nanoparticles allows easy characterization
      of the functional lines by atomic force microscopy (AFM) and scanning electron
      microscopy (SEM). Depending on the laser power and writing speed, functional
      lines with widths between 1.1 MUm and 250 nm can be created. In addition,
      trifluoroethyl-terminated (TFE) monolayers are also patterned. Subsequently, the
      decomposed lines are backfilled with a nonfunctional hexadecenyl monolayer, the
      TFE stripes are converted into thiol stripes, and then finally covered with Au
      nanoparticles. By reducing the lateral distance between the laser lines, Au
      nanoparticle stripes with widths close to 100 nm are obtained. Finally, in view
      of the great potential of this type of monolayer in the field of biosensing, the
      ease of fabricating biofunctional patterns is demonstrated by covalent binding of
      fluorescently labeled oligo-DNA to acid-fluoride-backfilled laser lines, which-
      as shown by fluorescence microscopy--is accessible for hybridization.

PMID- 20677185
TI  - Facile synthesis of bimetallic Ag/Ni core/sheath nanowires and their magnetic and
      electrical properties.
AB  - This paper describes a facile method for coating Ag nanowires with uniform,
      ferromagnetic sheaths made of polycrystalline Ni. A typical sample of these
      core/sheath nanowires had a saturation magnetization around 33 emu g(-1). We also
      demonstrated the use of this magnetic property to align the nanowires by simply
      placing a suspension of the nanowires on a substrate in a magnetic field and
      allowing the solvent to evaporate. The electrical conductivity of these
      core/sheath nanowires (2 * 10(3) S cm(-1)) was two orders of magnitude lower than
      that of bulk Ag (6.3 * 10(5) S cm(-1)) and Ni (1.4 * 10(5) S cm(-1)). This is
      likely caused by the transfer of electrons from the Ag core to the Ni sheath due
      to the difference in work function between the two metals. The electrons are
      expected to experience an increased resistance due to spin-dependent scattering
      caused by the randomized magnetic domains in the polycrystalline, ferromagnetic
      Ni sheath. Studies on the structural changes to the Ni coating over time under
      different storage conditions show that storage of the nanowires on a substrate
      under ambient conditions leads to very little Ni oxidation after 6 months. These
      Ag/Ni core/sheath nanowires show promise in areas such as electronics,
      spintronics, and displays.

PMID- 20677186
TI  - Optical visualization of carbon nanotubes-a unifying linkage between microscopic
      and spectroscopic characterization techniques.

PMID- 20677187
TI  - Photo-rechargeable battery effect in first generation cationic-cyanine
      dendrimers.

PMID- 20677188
TI  - Diffusion of adhesion layer metals controls nanoscale memristive switching.

PMID- 20677189
TI  - Single-InN-nanowire nanogenerator with upto 1 V output voltage.

PMID- 20677191
TI  - Co-adsorption of O and H(2)O on nanostructured platinum surfaces: Does OH form at
      steps?

PMID- 20677190
TI  - Reversible conversion of the majority carrier type in solution-processed
      ambipolar quinoidal oligothiophene thin films.

PMID- 20677192
TI  - Synthesis and structure of a base-stabilized C-phosphino-Si-amino silyne.

PMID- 20677194
TI  - InI3- or ZnI2-catalyzed reaction of hydroxylated 1,5-allenynes with thiols: a new
      access to 3,5-disubstituted toluene derivatives.
AB  - Transition-metal-activated alkynes or allenes can accept nucleophilic attack and
      undergo direct addition of the nucleophiles to the unsaturated bonds or trigger
      subsequent rearrangement reactions. This chemistry has witnessed increasing
      development in recent years. In this report, we have focused on the metal
      catalyzed reactions of a variety of substituted propargyl allenic alcohols and
      thiophenols using indium(III) and zinc(II) catalysts, which can activate both the
      alcohol and alkyne. In this reaction, thio groups play the role of a nucleophile
      and trigger subsequent rearrangements to give benzene derivatives. The products
      can be further transformed into various 1,3,5-trisubstituted aromatic compounds
      by nickel-catalyzed coupling reactions through the cleavage of the C-S bonds.

PMID- 20677195
TI  - para-Phenylene-bridged spirobi(triarylamine) dimer with four perpendicularly
      linked redox-active pi systems.
AB  - para-Phenylene-bridged spirobi(triarylamine) dimer 2, in which pi conjugation
      through four redox-active triarylamine subunits is partially segregated by the
      unique perpendicular conformation, was prepared and characterized by structural,
      electrochemical, and spectroscopic methods. Quantum chemical calculations (DFT
      and CASSCF) predicted that the frontier molecular orbitals of 2 are virtually
      fourfold degenerate, so that the oxidized states of 2 can give intriguing
      electronic and magnetic properties. In fact, the continuous-wave ESR spectroscopy
      of radical cation 2(*+) showed that the unpaired electron was trapped in the
      inner two redox-active dianisylamine subunits, and moreover was fully delocalized
      over them. Magnetic susceptibility measurements and pulsed ESR spectroscopy of
      the isolated salts of 2, which can be prepared by treatment with SbCl(5),
      revealed that the generated tetracation 2(4+) decomposed mainly into a mixture of
      1) a decomposed tetra(radical cation) consisting of a tri(radical cation) moiety
      and a trianisylamine radical cation moiety (~75%) and 2) a diamagnetic quinoid
      dication in a tetraanisyl-p-phenylendiamine moiety and two trianisylamine radical
      cation moieties (~25%). Furthermore, the spin-quartet state of the tri(radical
      cation) moiety in the decomposed tetra(radical cation) was found to be in the
      ground state lying 30 cal mol(-1) below the competing spin-doublet state.

PMID- 20677196
TI  - Selenium- and tellurium-containing multifunctional redox agents as biochemical
      redox modulators with selective cytotoxicity.
AB  - Various human diseases, including different types of cancer, are associated with
      a disturbed intracellular redox balance and oxidative stress (OS). The past
      decade has witnessed the emergence of redox-modulating compounds able to utilize
      such pre-existing disturbances in the redox state of sick cells for therapeutic
      advantage. Selenium- and tellurium-based agents turn the oxidizing redox
      environment present in certain cancer cells into a lethal cocktail of reactive
      species that push these cells over a critical redox threshold and ultimately kill
      them through apoptosis. This kind of toxicity is highly selective: normal,
      healthy cells remain largely unaffected, since changes to their naturally low
      levels of oxidizing species produce little effect. To further improve
      selectivity, multifunctional sensor/effector agents are now required that
      recognize the biochemical signature of OS in target cells. The synthesis of such
      compounds provides interesting challenges for chemistry in the future.

PMID- 20677197
TI  - Polyguanidines as chiral orienting media for organic compounds.

PMID- 20677198
TI  - Enantioselective rearrangement of proline sulfonamides: an easy entry to
      enantiomerically pure alpha-aryl quaternary prolines.

PMID- 20677199
TI  - Hypervalent silicon compounds by coordination of diphosphine-silanes to gold.
AB  - Coordination of ambiphilic diphosphine-silane ligands [o
      (iPr(2)P)C(6)H(4)](2)Si(R)F (R=F, Ph, Me) to AuCl affords pentacoordinate neutral
      silicon compounds in which the metal atom acts as a Lewis base. X-ray diffraction
      analyses, NMR spectroscopy, and DFT calculations substantiate the presence of Au
      >Si interactions in these complexes, which result in trigonal-bipyramidal
      geometries around silicon. The presence of a single electron-withdrawing fluorine
      atom is sufficient to observe coordination of the silane as a sigma-acceptor
      ligand, provided it is positioned trans to gold. The nature of the second
      substituent at silicon (R=F, Ph, Me) has very little influence on the magnitude
      of the Au->Si interaction, in marked contrast to N->Si adducts. According to
      variable-temperature and 2D EXSY NMR experiments, the apical/equatorial positions
      around silicon exchange in the slow regime of the NMR timescale. The two forms,
      with the fluorine atom in trans or cis position to gold, were characterized
      spectroscopically and the activation barrier for their interconversion was
      estimated. The bonding and relative stability of the two isomeric structures were
      assessed by DFT calculations.

PMID- 20677200
TI  - A new versatile route for the conversion of phospholes into phosphinines.

PMID- 20677201
TI  - Significantly enhanced DNA thermal stability resulting from porphyrin H-aggregate
      formation in the minor groove of the duplex.

PMID- 20677202
TI  - Chemical synthesis and structure of the prokineticin Bv8.
AB  - Bv8, a 77-residue protein isolated from frogs, is the prototypic member of the
      prokineticin family of cytokines. Prokineticins (PKs) have only recently been
      identified in vertebrates (including humans), and they are believed to be
      involved in a number of key physiological processes, such as angiogenesis,
      neurogenesis, nociception, and tissue development. We used a combination of Boc
      solid-phase peptide synthesis, native chemical ligation, and in vitro protein
      folding to establish robust chemical access to this molecule. Synthetic Bv8 was
      obtained in good yield and exhibited full activity in a human neuroblastoma cell
      line and rat dorsal root ganglion (DRG) neurons. The 3D structure of the
      synthetic protein was determined by using NMR spectroscopy and it was found to be
      homologous with that of mamba intestinal toxin 1, which is the only other known
      prokineticin structure. Analysis of a truncated mutant lacking five residues at
      the N terminus that are critical for receptor binding and activation showed no
      perturbation to the core protein structure. Together with the functional data,
      this suggests that receptor binding is likely to be a highly cooperative process
      possibly involving major allosterically driven structural rearrangements. The
      facile and efficient synthesis presented here will enable preparation of unique
      chemical analogues of prokineticins, which should be powerful tools for
      modulating the structure and function of prokineticins and their receptors, and
      studying the many physiological processes that have been linked to them.

PMID- 20677203
TI  - Quantifying prefibrillar amyloids in vitro by using a "thioflavin-like"
      spectroscopic method.
AB  - In Alzheimer's disease (AD) and other neurodegenerative disorders, proteins
      accumulate into ordered aggregates, called amyloids. Recent evidence suggests
      that these structures include both large, insoluble fibrils and smaller,
      prefibrillar structures, such as dimers, oligomers, and protofibrils. Recently,
      focus has shifted to the prefibrillar aggregates because they are highly
      neurotoxic and their levels appear to correlate with cognitive impairment. Thus,
      there is interest in finding methods for specifically quantifying these
      structures. One of the classic ways of detecting amyloid formation is through the
      fluorescence of the benzothiazole dye, thioflavin T (ThT). This reagent has been
      a "workhorse" of the amyloid field because it is robust and inexpensive. However,
      one of its limitations is that it does not distinguish between prefibrillar and
      fibrillar aggregates. We screened a library of 37 indoles for those that
      selectively change fluorescence in the presence of prefibrillar amyloid-beta
      (Abeta). From this process, we selected the most promising example, tryptophanol
      (TROL), to use in a quantitative "thioflavin-like" assay. Using this probe in
      combination with electron microscopy, we found that prefibrils are largely
      depleted during Abeta aggregation in vitro but that they remain present after the
      apparent saturation of the ThT signal. These results suggest that a combination
      of TROL and ThT provides greater insight into the process of amyloid formation by
      Abeta. In addition, we found that TROL also recognizes other amyloid-prone
      proteins, including ataxin-3, amylin, and CsgA. Thus, this assay might be an
      inexpensive spectroscopic method for quantifying amyloid prefibrils in vitro.

PMID- 20677204
TI  - Aqueous ethylenediamine for CO(2) capture.
AB  - Aqueous ethylenediamine (EDA) has been investigated as a solvent for CO(2)
      capture from flue gas. EDA can be used at 12 M (mol kg(-1) H(2)O) with an
      acceptable viscosity of 16 cP (1 cP=10(-3) Pa s) with 0.48 mol CO(2) per
      equivalent of EDA. Similar to monoethanolamine (MEA), EDA can be used up to 120
      degrees C in a stripper without significant thermal degradation. Inhibitor A will
      effectively eliminate oxidative degradation. Above 120 degrees C, loaded EDA
      degrades with the production of its cyclic urea and other related compounds.
      Unlike piperazine, when exposed to oxidative degradation, EDA does not result in
      excessive foaming. Over much of the loading range, the CO(2) absorption rate with
      12 M EDA is comparable to 7 M MEA. However, at typical rich loading, 12 M EDA
      absorbs CO(2) 2 times slower than 7 M MEA. The capacity of 12 M EDA is 0.72 mol
      CO(2)/(kg H(2)O+EDA) (for P(CO(2) )=0.5 to 5 kPa at 40 degrees C), which is about
      double that of MEA. The apparent heat of CO(2) desorption in EDA solution is 84
      kJ mol(-1) CO(2); greater than most other amine systems.

PMID- 20677205
TI  - Computational comparison of the reactions of substituted amines with CO(2).
AB  - Substituted amines are a popular choice as molecules to selectively react with
      and separate CO(2) from gas mixtures. Such separations are of particular
      interest, for example, for CO(2) separations for carbon capture and
      sequestration. It is desirable to tune amine-CO(2) reaction energies to suit a
      particular separation. Herein, we use DFT-B3LYP simulations to characterize the
      products and energetics of reactions of CO(2) with a range of substituted amines,
      considering both 1:1 and 2:1 amine/CO(2) reaction stoichiometries. The results
      show that by adjusting both the nature and the placement of functional groups, it
      is possible to tune reaction energies over a substantial range. Decomposition of
      the 2:1 reaction into separate carbamate and ammonium formation steps shows that
      the Bronsted basicity and Lewis basicity towards CO(2) are largely uncorrelated
      and provide an independent means of tuning the overall reaction energies.

PMID- 20677206
TI  - Cleaving the beta--O--4 bonds of lignin model compounds in an acidic ionic
      liquid, 1-H-3-methylimidazolium chloride: an optional strategy for the
      degradation of lignin.
AB  - The hydrolysis of beta--O--4 bonds in two lignin model compounds was studied in
      an acidic ionic liquid, 1-H-3-methylimidazolium chloride. The beta--O--4 bonds of
      both guaiacylglycerol-beta-guaiacyl ether and veratrylglycerol-beta-guaiacyl
      ether underwent catalytic hydrolysis to produce guaiacol as the primary product
      with more than 70 % yield at 150  degrees C. Up to 32 wt % substrate
      concentration could be treated in the system without a decrease in guaiacol
      production. The ionic liquid could be reused without loss of activity in guaiacol
      production from both guaiacylglycerol-beta-guaiacyl ether and veratrylglycerol
      beta-guaiacyl ether. A possible mechanism accounting for the guaiacol production
      is presented.

PMID- 20677207
TI  - The development of a new type of rechargeable batteries based on hybrid
      electrolytes.
AB  - Lithium ion batteries (LIBs), which have the highest energy density among all
      currently available rechargeable batteries, have recently been considered for use
      in hybrid electric vehicles (HEVs), plug-in hybrid electric vehicles (PHEVs), and
      pure electric vehicles (PEV). A major challenge in this effort is to increase the
      energy density of LIBs to satisfy the industrial needs of HEVs, PHEVs, and PEVs.
      Recently, new types of lithium-air and lithium-copper batteries that employ
      hybrid electrolytes have attracted significant attention; these batteries are
      expected to succeed lithium ion batteries as next-generation power sources.
      Herein, we review the concept of hybrid electrolytes, as well as their advantages
      and disadvantages. In addition, we examine new battery types that use hybrid
      electrolytes.

PMID- 20677208
TI  - Characterization of tissue structure at varying length scales using temporal
      diffusion spectroscopy.
AB  - The concepts, theoretical behavior and experimental applications of temporal
      diffusion spectroscopy are reviewed and illustrated. Temporal diffusion spectra
      are obtained using oscillating-gradient waveforms in diffusion-weighted
      measurements, and represent the manner in which various spectral components of
      molecular velocity correlations vary in different geometrical structures that
      restrict or hinder free movements. Measurements made at different gradient
      frequencies reveal information on the scale of restrictions or hindrances to free
      diffusion, and the shape of a spectrum reveals the relative contributions of
      spatial restrictions at different distance scales. Such spectra differ from other
      so-called diffusion spectra which depict spatial frequencies and are defined at a
      fixed diffusion time. Experimentally, oscillating gradients at moderate frequency
      are more feasible for exploring restrictions at very short distances which, in
      tissues, correspond to structures smaller than cells. We describe the underlying
      concepts of temporal diffusion spectra and provide analytical expressions for the
      behavior of the diffusion coefficient as a function of gradient frequency in
      simple geometries with different dimensions. Diffusion in more complex model
      media that mimic tissues has been simulated using numerical methods. Experimental
      measurements of diffusion spectra have been obtained in suspensions of particles
      and cells, as well as in vivo in intact animals. An observation of particular
      interest is the increased contrast and heterogeneity observed in tumors using
      oscillating gradients at moderate frequency compared with conventional pulse
      gradient methods, and the potential for detecting changes in tumors early in
      their response to treatment. Computer simulations suggest that diffusion spectral
      measurements may be sensitive to intracellular structures, such as nuclear size,
      and that changes in tissue diffusion properties may be measured before there are
      changes in cell density.

PMID- 20677209
TI  - Gaining the hard yard: pre-clinical evaluation of lentiviral-mediated gene
      therapy for the treatment of beta-thalassemia.
AB  - Gene therapy is one potential novel therapeutic avenue for the treatment of
      inherited monogenic disorders. Diseases of the blood are frequent targets for
      gene therapy because it is relatively easy to harvest haematopoiesis stem cells
      (HSCs) from the bone marrow, genetically modify the cells ex vivo, and then re
      administer the corrected cells back into the patient via intra-venous injection.
      In this Closeup, Milsom and Williams discuss the work of Roselli et al, who
      describe the pre-clinical evaluation of the treatment for beta-thalassemia in
      erythroid cells via the genetic correction of patient HSCs using a lentiviral
      vector.

PMID- 20677210
TI  - Pathogens under scrutiny in the south of France.
AB  - The first EMBO workshop on Emerging Themes in Infection Biology was held last
      June in the South of France. It gathered scientists working on various pathogens
      from viruses and bacteria to larger eukaryotic fungi and parasites. Topics
      included not only the crosstalk between pathogens and their hosts but also the
      tools researchers are using to study and image such cellular and molecular
      conversations.

PMID- 20677211
TI  - Upper gastrointestinal bleeding in a patient with defective hemostasis
      successfully treated with ankaferd blood stopper.
AB  - Acute gastrointestinal (GI) bleeding is one of the most frequent causes for
      hospitalization and responsible for a major cause of morbidity and mortality
      among patients. Ankaferd Blood Stopper (ABS) is a herbal extract attained from
      five different plants Thymus vulgaris, Glycyrrhiza glabra, Vitis vinifera,
      Alpinia officinarum and Urtica dioica. Here we report a challenging upper GI
      bleeding case with a low platelet count and defective hemostasis treated
      endoscopically with ABS as an adjunctive drug.

PMID- 20677212
TI  - Inter-laboratory validation of the modified murine local lymph node assay based
      on 5-bromo-2'-deoxyuridine incorporation.
AB  - The murine local lymph node assay (LLNA) is a well-established alternative to the
      guinea pig maximization test (GPMT) or Buehler test (BT) for the assessment of
      the skin sensitizing ability of a drug, cosmetic material, pesticide or
      industrial chemical. Instead of radioisotope using in this method, Takeyoshi M.
      et al. (2001) has developed a modified LLNA based on the 5-bromo-2'-deoxyuridine
      (BrdU) incorporation (LLNA:BrdU-ELISA). The LLNA:BrdU-ELISA is practically
      identical to the LLNA methodology excluding the use of BrdU, for which a single
      intraperitoneal injection of BrdU is made on day 4, and colorimetric detection of
      cell turnover. We conducted the validation study to evaluate the reliability and
      relevance of LLNA:BrdU-ELISA. The experiment involved 7 laboratories, wherein 10
      chemicals were examined under blinded conditions. In this study, 3 chemicals were
      examined in all laboratories and the remaining 7 were examined in 3 laboratories.
      The data were expressed as the BrdU incorporation using an ELISA method for each
      group, and the stimulation index (SI) for each chemical-treated group was
      determined as the increase in the BrdU incorporation relative to the concurrent
      vehicle control group. An SI of 2 was set as the cut-off value for exhibiting
      skin sensitization activity. The results obtained in the experiments conducted
      for all 10 chemicals were sufficiently consistent with small variations in their
      SI values. The sensitivity, specificity, and accuracy of LLNA:BrdU-ELISA against
      those of GPMT/BT were 7/7 (100%), 3/3 (100%), and 10/10 (100%), respectively.

PMID- 20677213
TI  - B0 inhomogeneity-insensitive triple-quantum-filtered sodium imaging using a 12
      step phase-cycling scheme.
AB  - Triple-quantum-filtered (TQF) sodium MRI can be used to separate sodium NMR
      signals from different physiological compartments. Although three-pulse triple
      quantum filtering has been demonstrated to be better suited for in vivo imaging,
      the absence of the refocusing pulse in the filter increases its sensitivity to
      magnetic field inhomogeneities. Therefore, several TQF cycles have been developed
      previously to correct image distortions caused by B(0) inhomogeneities. In this
      paper, we present a new 12-step phase-cycling TQF scheme based on three
      radiofrequency pulses which allows the compensation of B(0) variations both with
      and without ancillary B(0) map information. The method offers 40% higher signal
      to-noise-ratio efficiency compared with the previously developed B(0)-correcting
      phase-cycling schemes.

PMID- 20677214
TI  - Towards integrated community mental health teams for older people in England:
      progress and new insights.
AB  - OBJECTIVE: To investigate progress in joint working within community mental
      health teams for older people (CMHTsOP) against a range of national standards,
      and to consider team characteristics that may hinder or facilitate integrated
      practice. METHODS: A postal questionnaire was sent to the managers of all CMHTsOP
      in England. A total of 376 teams responded representing a response rate of 87.7%.
      Hypothesis testing and regression analysis, using a composite score based on nine
      indicators of integration, were conducted to address the study's aims. RESULTS:
      Whilst the study suggests that progress was being made against a number of key
      standards of joint working, the study finds that most teams could not access
      local authority service user records, nor were health staff within most teams
      able to commission social care services. After controlling for other
      characteristics, teams with the lowest levels of integration tended to work
      across multiple local authorities; were managed by a nurse; had high referral
      rates and were located in formally integrated Care Trusts. CONCLUSIONS: Improved
      integration could develop by NHS Trusts and local authorities encouraging more
      information sharing, and further delegating powers to arrange social care
      services to CMHTOP members. The paper highlights team and locality features that
      appear to cause obstacles to joint working, but there is a clear gap in the
      evidence relating team structures and characteristics to the quality of patient
      care.

PMID- 20677215
TI  - Modulators of cancer cell invasiveness.
AB  - Cell invasiveness is essential for cancer metastasis. Many proteins, and more
      recently also non-coding RNAs, particularly microRNAs (miRNAs), have been
      reported to affect the cell invasiveness of various cancers. There is an apparent
      gap between the high number of these macromolecules and the low number of
      signaling pathways experimentally verified to control cancer invasiveness. We
      have brought together these various proteins and RNAs because we could not find
      any publication that filled this important gap. We have noted 589 proteins, 28
      miRNAs, and 1 long non-coding RNA that are reported to modulate invasiveness in
      cells of various cancers. Interestingly, 44 proteins enhance invasiveness in
      cells of some cancers, but suppress it in cells of others. Almost all of the
      proteins that show experimentally verified activation/inhibition effects on, or
      binding interactions with, each other are linked together in a single network, in
      a "hub-and-spoke" architecture. The accumulated data show trends that point to
      anticipated future results and highlight gaps in what is known about invasiveness
      signaling. Identification of cancer invasiveness signaling networks is important
      for combination and personalized targeted therapies of cancers.

PMID- 20677216
TI  - Characterization of murine SIRT3 transcript variants and corresponding protein
      products.
AB  - SIRT3 is one of the seven mammalian sirtuin homologs of the yeast SIR2 gene.
      SIRT3 possesses NAD(+)-dependent protein deacetylase activity. Recent studies
      indicate that the murine SIRT3 gene expresses different transcript variants,
      resulting in three possible SIRT3 protein isoforms with various lengths at the N
      terminus: M1 (aa 1-334), M2 (aa 15-334), and M3 (aa 78-334). The transcript
      variants 1 and 3 can only produce M3 protein, while M1 and M2 proteins are
      translationally initiated from different in-frame ATG sites in transcript 2. Here
      we report that three transcript variants of the mouse SIRT3 gene are broadly
      expressed in various mouse tissues. By expressing these SIRT3 isoforms in HEK293
      cells through transient transfection, we confirmed recent reports that two longer
      murine SIRT3 proteins (M1 and M2) are targeted to mitochondria with higher
      efficiency than the shorter M3 isoform. Additionally, the M1 and M2 proteins are
      processed into a mature form. Using Edman degradation we identify Ile38
      (majority) or Val42 as the N-terminal amino acid of the mature M1 isoform, and
      Met78 or Val79 as the N-terminal amino acid of the M3 isoform. Interestingly, we
      found that even upon mutation of the M2 ATG site in the M1 cDNA, a processed
      mature protein could still be produced. In terms of deacetylase activity, we
      found that although only the mature protein derived from M1 or M2 proteins were
      active against acetylated peptide substrates, all three forms had equal
      deacetylase activity towards a full-length native protein substrate, acetyl CoA
      synthetase 2.

PMID- 20677217
TI  - Sepsis downregulates myostatin mRNA levels without altering myostatin protein
      levels in skeletal muscle.
AB  - Myostatin is a negative regulator of muscle mass and has been reported to be
      upregulated in several conditions characterized by muscle atrophy. The influence
      of sepsis on myostatin expression and activity is poorly understood. Here, we
      tested the hypothesis that sepsis upregulates the expression and downstream
      signaling of myostatin in skeletal muscle. Because sepsis-induced muscle wasting
      is at least in part regulated by glucocorticoids, we also determined the
      influence of glucocorticoids on myostatin expression. Sepsis was induced in rats
      by cecal ligation and puncture and control rats were sham-operated. In other
      experiments, rats were injected intraperitoneally with dexamethasone (10 mg/kg)
      or corresponding volume of vehicle. Surprisingly, myostatin mRNA levels were
      reduced and myostatin protein levels were unchanged in muscles from septic rats.
      Muscle levels of activin A, follistatin, and total and phosphorylated Smad2 (p
      Smad2) were not influenced by sepsis, suggesting that myostatin downstream
      signaling was not altered during sepsis. Interestingly, total and p-Smad3 levels
      were increased in septic muscle, possibly reflecting altered signaling through
      pathways other than myostatin. Similar to sepsis, treatment of rats with
      dexamethasone reduced myostatin mRNA levels and did not alter myostatin protein
      levels. Fasting, an additional condition characterized by muscle wasting, reduced
      myostatin mRNA and activin A protein levels, increased myostatin protein, and did
      not influence follistatin and p-Smad2 levels. Of note, total and p-Smad3 levels
      were reduced in muscle during fasting. The results suggest that sepsis and
      glucocorticoids do not upregulate the expression and activity of myostatin in
      skeletal muscle. The role of myostatin may vary between different conditions
      characterized by muscle wasting. Downstream signaling through Smad2 and 3 is
      probably regulated not only by myostatin but by other mechanisms as well.

PMID- 20677218
TI  - Ultra scale-down stress analysis of the bioprocessing of whole human cells as a
      basis for cancer vaccines.
AB  - This study examines the use of a capillary shear device for the rapid
      characterization of human cell lines in terms of their resistance to hydrodynamic
      stress. An ultra scale-down (USD) approach is presented to allow the use of small
      quantities of cells available at the early discovery stage and to expose them to
      a wide range of hydrodynamic stresses. In this way an indication is gained of the
      relative properties of different cell lines and the challenge which may be faced
      during full-scale processing. A design of experiments approach allowed the
      interaction between a number of key processing factors such as capillary length,
      flow rate, and number of passes to be studied in a limited number of experiments.
      Out of this an USD test based on flow rate in a device of fixed geometry was
      proposed. Based on observations made elsewhere (Ma et al., 2002, Biotechnol
      Bioeng 80(4): 428-437) a detailed analysis of possible geometries was performed
      using a combination of USD experiments and computational fluid dynamics analysis
      of the capillary entry region. This allowed the properties of the cells to be
      characterized in terms of a critical stress below which there is no significant
      loss of cell integrity. The results suggested that the OnyCap23 and P4E6 cell
      lines, used as components of a whole cell prostate cancer vaccine, are resistant
      to damage below critical elongational shear stress values of 235 and 275 N/m(2),
      respectively. Above these stress values the loss of intact cells is predicted to
      be significant; such loss being due to a combination of whole cells becoming
      permeable to trypan blue and complete breakage of cells into debris at extreme
      stresses. The sensitivity of cell surface markers CD9, CD44, CD59, CD81, CD147,
      and MHC-1 to exposure to shear stress was considerably less than for cell
      membrane integrity. The surface marker levels for recovered whole cells (i.e.,
      both with and without intact cell membranes) were either independent of shear
      stress or showed a slight decrease with increased shear stress, for example, as
      for CD9. The results were used to predict successfully a capillary design where
      no damage would occur at a specified high flow rate; for example, as required for
      cell dispensing or vialling operations. Equally, the extent of loss of cell
      integrity was also successfully predicted in a capillary flow system designed to
      yield high levels of break up as may be required in intracellular analysis
      without the use of chemical lysing reagents or relying on autolytic damage.

PMID- 20677219
TI  - Gender differences in beta-adrenoceptor system in cardiac hypertrophy due to
      arteriovenous fistula.
AB  - This study was undertaken to determine alterations in the beta-adrenoceptor (beta
      AR) signaling system in male and female rats at 4 weeks after the induction of
      arteriovenous (AV) fistula or shunt. AV shunt produced a greater degree of
      cardiac hypertrophy and larger increase in cardiac output in male than in female
      animals. Increases in plasma levels of norepinephrine and epinephrine (EPI) due
      to AV shunt were also higher in male than females. While no difference in the
      beta(1)-AR affinity was seen in males and females, AV shunt induced increase in
      beta(1)-AR density in female rats was higher than that in males. Furthermore, no
      changes in basal adenylyl cyclase (AC) V/VI mRNA levels were seen; however, the
      increase in EPI-stimulated AC activities was greater in AV shunt females than in
      males. AV shunt decreased myocardial beta(1)-AR mRNA level in male rats and
      increased beta(2)-AR mRNA level in female hearts; an increase in G(i)-protein
      mRNA was detected only in male hearts. Although GRK2 gene expression was
      increased in both sexes, an increase in GRK3 mRNA was seen only in AV shunt
      female rats. beta-arrestin1 mRNA was elevated in females whereas beta-arrestin 2
      gene expression was increased in both male and female AV shunt rats. While these
      data demonstrate gender associated differences in various components of the beta
      AR system in cardiac hypertrophy due to AV shunt, only higher levels of plasma
      catecholamines may account for the greater increase in cardiac output and higher
      degree of cardiac hypertrophy in males.

PMID- 20677220
TI  - Breast cancer surgery-induced immunomodulation.
AB  - BACKGROUND AND OBJECTIVES: Surgical procedures can cause tumor cells to
      disseminate into the circulatory system. Although this spread of metastatic cells
      will be limited by immune activity, immunosuppression tends to be the main effect
      resulting from surgery. The objective of this study is to assess hormonal and
      immunological changes induced by breast cancer surgery. METHODS: Endocrine and
      immune responses to surgery were determined in 27 breast cancer patients. Blood
      samples were taken at 6 days and 1 day before surgery and 2 hr, 1 day, and 5 days
      after surgery. Changes in endocrine function, number of leucocytes and their
      subpopulations, enumerative immune expression, functional activity, and cytokine
      levels were determined. RESULTS: Breast cancer surgery induces a pro-inflammatory
      response and leucocytosis. Immunosuppression is indicated by decreased HLA-DR
      expression, decreased NKCA, and a Th2 response. A delayed Th1 response was also
      found 5 days after surgery. As no cortisol level change was observed, this
      hormone can be excluded as the mediator of surgery-related immunomodulation in
      breast cancer. CONCLUSION: Although breast cancer surgery is classified as minor
      surgery the surgical procedure produces substantial immunomodulation.

PMID- 20677221
TI  - Significance of the resection of ovarian metastasis from colorectal cancers.
AB  - BACKGROUND: The incidence of ovarian metastases from colorectal cancers (CRCs)
      has been reported to occur in 3-8% of CRC patients, and the prognosis for
      patients is very poor. We assessed the clinicopathological characteristics of CRC
      patients with ovarian metastasis and the significance of the resection of ovarian
      metastases. METHODS: We retrospectively analyzed 22 CRC patients with ovarian
      metastases. Synchronous ovarian metastases occurred in 8 patients and
      metachronous ovarian metastases occurred in 14 patients. Peritoneal dissemination
      was observed in nine patients. RESULTS: The mean follow-up period was 45.3
      months. The overall survival at 3 years following diagnosis of ovarian metastases
      is estimated to be 51.1% and 43.8% at 5 years. The overall survival at 5 years in
      the group of patients without peritoneal disseminations was 77.9%, which is
      significantly longer than that of the patients with disseminations (0%) (P =
      0.0009). An R0 resection of metastatic sites was achieved in 15 patients and was
      associated with a significant increase in survival time (P = 0.0002).
      CONCLUSIONS: Our study shows that aggressive resection of ovarian metastases from
      CRCs is associated with better overall survival. Peritoneal dissemination is an
      adverse prognostic factor, but R0 resection significantly improves the overall
      survival of these patients.

PMID- 20677222
TI  - The bone marrow microenvironment contributes to type I diabetes induced
      osteoblast death.
AB  - Type I diabetes increases an individual's risk for bone loss and fracture,
      predominantly through suppression of osteoblast activity (bone formation). During
      diabetes onset, levels of blood glucose and pro-inflammatory cytokines (including
      tumor necrosis factor alpha (TNFalpha)) increased. At the same time, levels of
      osteoblast markers are rapidly decreased and stay decreased chronically (i.e., 40
      days later) at which point bone loss is clearly evident. We hypothesized that
      early bone marrow inflammation can promote osteoblast death and hence reduced
      osteoblast markers. Indeed, examination of type I diabetic mouse bones
      demonstrates a greater than twofold increase in osteoblast TUNEL staining and
      increased expression of pro-apoptotic factors. Osteoblast death was amplified in
      both pharmacologic and spontaneous diabetic mouse models. Given the known
      signaling and inter-relationships between marrow cells and osteoblasts, we
      examined the role of diabetic marrow in causing the osteoblast death. Co-culture
      studies demonstrate that compared to control marrow cells, diabetic bone marrow
      cells increase osteoblast (MC3T3 and bone marrow derived) caspase 3 activity and
      the ratio of Bax/Bcl-2 expression. Mouse blood glucose levels positively
      correlated with bone marrow induced osteoblast death and negatively correlated
      with osteocalcin expression in bone, suggesting a relationship between type I
      diabetes, bone marrow and osteoblast death. TNF expression was elevated in
      diabetic marrow (but not co-cultured osteoblasts); therefore, we treated co
      cultures with TNFalpha neutralizing antibodies. The antibody protected
      osteoblasts from bone marrow induced death. Taken together, our findings
      implicate the bone marrow microenvironment and TNFalpha in mediating osteoblast
      death and contributing to type I diabetic bone loss.

PMID- 20677223
TI  - Role of hypoxia-induced fibronectin-integrin beta1 expression in embryonic stem
      cell proliferation and migration: Involvement of PI3K/Akt and FAK.
AB  - Cell migration is largely dependent on integrin (IN) binding to the extracellular
      matrix, and several signaling pathways involved in these processes have been
      shown to be modified by hypoxia. Therefore, the aim of this study was to
      determine the influence of hypoxia on fibronectin (FN) and IN beta1 expression in
      mouse embryonic stem cells (mESCs) and their signaling pathways to modulate
      proliferation. FN and IN beta1 expression were significantly increased in hypoxic
      mESCs by 24 h. Hypoxia also increased cell attachment, which was accompanied by
      concomitant increases in the binding level of FN and IN beta1. Hypoxia-induced FN
      expression was mediated by increased phosphatidylinositol 3 kinase (PI3K)/Akt and
      mammalian target of rapamycin (mTOR) phosphorylation, and hypoxia-inducible
      factor-1alpha (HIF-1alpha) expression. Moreover, under hypoxic conditions, focal
      adhesion kinase (FAK) and Src phosphorylation were increased in a time-dependent
      fashion; these increases were blocked by IN beta1 antibody. In addition, the
      hypoxia induced increase of F-actin distribution and cell migration (activation
      of matrix metalloproteinase-2 and -9) was inhibited by IN beta1 antibody. Indeed,
      hypoxia increased the level of cell-cycle regulatory protein and DNA synthesis.
      In conclusion, hypoxia increases the proliferation and migration of mESCs via FN
      IN beta1 production through the PI3K/Akt, mTOR, and HIF-1alpha pathways, followed
      by FAK activation.

PMID- 20677224
TI  - Primates in 21st century ecosystems: does primate conservation promote ecosystem
      conservation?
AB  - Contributors to this issue of the American Journal of Primatology were among the
      participants in an invited symposium at the 2008 Association for Tropical Biology
      and Conservation meeting in Paramaribo, Suriname. They were asked to assess how
      essential primates are to tropical ecosystems and, given their research
      interests, discuss how primate research contributes to the broader understanding
      about how ecosystems function. This introduction to the issue is divided into
      three parts: a review of the roles that nonhuman primates play in tropical
      ecosystems; the implementation of large-scale landscape methods used to identify
      primate densities; and concerns about the increasingly porous boundaries between
      humans, nonhuman primates, and pathogens. Although 20th century primate research
      created a rich database on individual species, including both theoretical and
      descriptive approaches, the dual effects of high human population densities and
      widespread habitat destruction should warn us that creative, interdisciplinary
      and human-related research is needed to solve 21st century problems.

PMID- 20677225
TI  - Reproductive characteristics of wild female Phayre's leaf monkeys.
AB  - Understanding female reproductive characteristics is important for assessing
      fertility, interpreting female behavior, and designing appropriate conservation
      and captive management plans. In primate species lacking morphological signs of
      receptivity, such as most colobines, determination of reproductive parameters
      depends on the analysis of reproductive hormones. Here, we use fecal hormone
      analysis to characterize cycle patterns (N=6 females) and gestation length (N=7
      females) in a group of wild Phayre's leaf monkeys (Trachypithecus phayrei
      crepusculus) in Phu Khieo Wildlife Sanctuary, Thailand. We found that both fecal
      estrogen (fE) and progestin (fP) levels showed clear biological patterns
      indicative of ovulation and conception. However, because fP patterns were
      inadequate in determining the end of the luteal phase, we used fE rather than fP
      patterns to delineate menstrual cycle parameters. We found a mean cycle length of
      28.4 days (N=10), with follicular and luteal phases of 15.4 (N=10) and 12.5 days
      (N=14), respectively. On average, females underwent 3.57 (N=7) cycles until
      conception. Average gestation length was 205.3 days (N=7), with fE levels
      increasing over the course of pregnancy. Overall, the reproductive
      characteristics found for Phayre's leaf monkeys were consistent with results for
      other colobine species, suggesting that fecal hormone monitoring, particularly
      for fE metabolites, can provide useful reproductive information for this species.

PMID- 20677226
TI  - Syngas fermentation to biofuel: evaluation of carbon monoxide mass transfer
      coefficient (kLa) in different reactor configurations.
AB  - Lignocellulosic biomass such as agri-residues, agri-processing by-products, and
      energy crops do not compete with food and feed, and is considered to be the ideal
      renewable feedstocks for biofuel production. Gasification of biomass produces
      synthesis gas (syngas), a mixture primarily consisting of CO and H(2). The
      produced syngas can be converted to ethanol by anaerobic microbial catalysts
      especially acetogenic bacteria such as various clostridia species.One of the
      major drawbacks associated with syngas fermentation is the mass transfer
      limitation of these sparingly soluble gases in the aqueous phase. One way of
      addressing this issue is the improvement in reactor design to achieve a higher
      volumetric mass transfer coefficient (k(L)a). In this study, different reactor
      configurations such as a column diffuser, a 20-MUm bulb diffuser, gas sparger,
      gas sparger with mechanical mixing, air-lift reactor combined with a 20-MUm bulb
      diffuser, air-lift reactor combined with a single gas entry point, and a
      submerged composite hollow fiber membrane (CHFM) module were employed to examine
      the k(L) a values. The k(L) a values reported in this study ranged from 0.4 to
      91.08 h(-1). The highest k(L) a of 91.08 h(-1) was obtained in the air-lift
      reactor combined with a 20-MUm bulb diffuser, whereas the reactor with the CHFM
      showed the lowest k(L) a of 0.4 h(-1). By considering both the k(L) a value and
      the statistical significance of each configuration, the air-lift reactor combined
      with a 20-MUm bulb diffuser was found to be the ideal reactor configuration for
      carbon monoxide mass transfer in an aqueous phase.

PMID- 20677227
TI  - A rare case of pacemaker electrode perforation of the heart with intra-abdominal
      migration.

PMID- 20677228
TI  - Adaptive black blood fast spin echo for end-systolic rest cardiac imaging.
AB  - Black Blood Fast Spin Echo imaging of the heart is usually performed during mid
      diastolic rest. This is a direct consequence of the long inversion time required
      to suppress the blood signal, which is constrained by the T(1) of the blood, and
      of the heart rate. To overcome these constraints, and to acquire black blood
      images in the end-systolic rest period, a new approach is introduced aiming at
      adaptively predicting the best time to prepare and acquire MR signals. It is
      based on a RR interval prediction algorithm and on a cardiac cycle model. The
      proposed method was applied to 14 healthy volunteers and is compared to a simple
      alternative method using a fixed delay and to the standard black blood imaging
      method for imaging in the mid-diastolic rest period. Results show that the
      proposed method offers an increased robustness in terms of trigger delay error
      and image quality compared to the tested simple alternative. Also, it has been
      shown by qualitative analysis done by an experienced observer that the right
      ventricle, especially the thin right ventricle free wall, is better depicted with
      our method than with the standard mid-diastolic rest acquisition.

PMID- 20677230
TI  - Simplified synthesis and relaxometry of magnetoferritin for magnetic resonance
      imaging.
AB  - Magnetoferritin nanoparticles have been developed as high-relaxivity, functional
      contrast agents for MRI. Several previous techniques have relied on unloading
      native ferritin and re-incorporation of iron into the core, often resulting in a
      polydisperse sample. Here, a simplified technique is developed using commercially
      available horse spleen apoferritin to create monodisperse magnetoferritin. Iron
      oxide atoms were incorporated into the protein core via a step-wise
      Fe(II)Chloride addition to the protein solution under low O(2) conditions;
      subsequent filtration steps allow for separation of completely filled and
      superparamagnetic magnetoferritin from the partially filled ferritin. This method
      yields a monodisperse and homogenous solution of spherical particles with
      magnetic properties that can be used for molecular magnetic resonance imaging.
      With a transverse per-iron and per-particle relaxivity of 78 mM(-1) sec(-1) and
      404,045 mM(-1) sec(-1), respectively, it is possible to detect ~ 10 nM
      nanoparticle concentrations in vivo.

PMID- 20677229
TI  - Magnetization transfer ratio mapping of intervertebral disc degeneration.
AB  - The magnetization transfer ratio of the lumbar discs was spatially quantified
      from age-matched subjects and the nucleus pulposus magnetization transfer ratio
      was correlated with T2-weighted Pfirrmann grades. A moderate and significant
      linear correlation between magnetization transfer ratio and Pfirrmann grades was
      observed, suggesting that nucleus pulposus collagen relative density increases
      with degeneration. High-resolution axial magnetization transfer ratio maps
      revealed elevated magnetization transfer ratio in the nucleus pulposa of injured
      and heavily degenerated discs. In the injured disc, significant elevation in
      nucleus pulposa magnetization transfer ratio was not accompanied by significant
      decrease in disc height. This observation may suggest a possible increase in
      absolute collagen content, in addition to increased collagen relative density. In
      summary, magnetization transfer MRI of the disc may serve as a noninvasive
      diagnostic tool for disc degeneration, in addition to other MRI techniques
      specific to proteoglycan content.

PMID- 20677231
TI  - A general framework for the analysis of vessel encoded arterial spin labeling for
      vascular territory mapping.
AB  - Vessel encoded arterial spin labeling provides a way to perform non-invasive
      vascular territory imaging. By uniquely encoding the blood within feeding
      arteries over a number of images, the territories of each can be identified.
      Here, a new approach for the analysis of vessel encoded arterial spin labeling
      data is presented. The method includes a full description of how the geometry of
      arteries and spatial label modulation affects the measured signal. It also
      incorporates an artery-based classification that considers multiple arteries in
      each class, explicitly permitting a voxel to be supplied by multiple arteries.
      The developed framework is cast within a Bayesian inference procedure allowing
      both flow contributions and the locations of the arteries in the labeling plane
      to be inferred. By using simulated data, the method was shown to provide more
      accurate estimates of blood contribution in areas of mixed supply, such as would
      be found in watershed regions, than conventional methods. It was also able to
      estimate the location of arteries within the labeling plane, accounting for
      motion between sequence prescription and acquisition. Similar performance was
      found for data acquired using a pseudo-continuous labeling scheme both in the
      neck and above the Circle of Willis.

PMID- 20677232
TI  - Measurement of arterial plasma oxygenation in dynamic oxygen-enhanced MRI.
AB  - Inhaled oxygen can be used as a contrast agent for magnetic resonance imaging,
      due to the T(1) shortening effect of the oxygen dissolved in blood and tissue
      water. In this study, blood T(1) was measured dynamically in 14 volunteers (seven
      smokers, seven never-smokers) as the inhaled gas was switched from medical air to
      100% oxygen and back to medical air. These T(1) values were converted to changes
      in partial pressure of oxygen, which were found to be in agreement with
      literature values. There were differences in curve shape and curve height between
      the smoker and never-smoker groups, suggesting differences in lung function due
      to smoking-related damage. These curves could be used as an input function for
      modeling of oxygen uptake in tissues. The differences between groups highlight
      the importance of measuring such an input function for each individual rather
      than relying on an assumed measurement.

PMID- 20677233
TI  - Alternate ascending/descending directional navigation approach for imaging
      magnetization transfer asymmetry.
AB  - A new method for imaging magnetization transfer (MT) asymmetry with no separate
      saturation pulse is proposed in this article. MT effects were generated from
      sequential two-dimensional balanced steady-state free precession imaging, where
      interslice MT asymmetry was separated from interslice blood flow and magnetic
      field inhomogeneity with alternate ascending/descending directional navigation
      (ALADDIN). Alternate ascending/descending directional navigation provided high
      resolution multislice MT asymmetry images within a reasonable imaging time of ~ 3
      min. MT asymmetry signals measured with alternate ascending/descending
      directional navigation were 1-2% of baseline signals (N = 6), in agreement with
      those from the conventional methods. About 70% of MT asymmetry signals were
      determined by the first prior slice. The frequency offset ranges in this study
      were >8 ppm from the water resonance frequency, implying that the MT effects were
      mostly associated with solid-like macromolecules. Potential methods to make
      alternate ascending/descending directional navigation feasible for imaging amide
      proton transfer (~ 3.5 ppm offset from the water resonance frequency) were
      discussed.

PMID- 20677234
TI  - Measurement of intervertebral disc pressure with T 1rho MRI.
AB  - The aim of this study is to demonstrate T(1rho) MRI's capability for measuring
      intervertebral disc osmotic pressure. Self-coregistered sodium and T(1rho) 
      weighted MR images were acquired on ex vivo bovine intervertebral discs (N = 12)
      on a 3 T clinical MRI scanner. The sodium MR images were used to calculate
      effective nucleus pulposus fixed-charge-density (mean = 138.2 +/- 27.6 mM) and
      subsequently osmotic pressure (mean = 0.53 +/- 0.18 atm), whereas the T(1rho) 
      weighted images were used to compute T(1rho) relaxation maps. A significant
      linear correlation (R = 0.56, P < 0.01) between nucleus pulposus fixed-charge
      density and T(1rho) relaxation time constant was observed. More importantly, a
      significant power correlation (R = 0.72, P < 0.01) between nucleus pulposus
      osmotic pressure as predicted by sodium MRI and T(1rho) relaxation time constant
      was also observed. The current clinical method for assessing disc pressure is
      discography, which is an invasive procedure that has been shown to have negative
      effects on disc biomechanical and biochemical properties. In contrast, T(1rho)
      MRI is noninvasive and can be easily implemented in a clinical setting due to its
      superior signal-to-noise ratio compared with sodium MRI. Therefore, T(1rho) MRI
      may serve as a noninvasive clinical tool for the longitudinal evaluation of disc
      osmotic pressure.

PMID- 20677235
TI  - Time-resolved absolute velocity quantification with projections.
AB  - Quantitative information on time-resolved blood velocity along the
      femoral/popliteal artery can provide clinical information on peripheral arterial
      disease and complement MR angiography as not all stenoses are hemodynamically
      significant. The key disadvantages of the most widely used approach to time
      resolve pulsatile blood flow by cardiac-gated velocity-encoded gradient-echo
      imaging are gating errors and long acquisition time. Here, we demonstrate a rapid
      nontriggered method that quantifies absolute velocity on the basis of phase
      difference between successive velocity-encoded projections after selectively
      removing the background static tissue signal via a reference image. The tissue
      signal from the reference image's center k-space line is isolated by masking out
      the vessels in the image domain. The performance of the technique, in terms of
      reproducibility and agreement with results obtained with conventional phase
      contrast-MRI was evaluated at 3 T field strength with a variable-flow rate
      phantom and in vivo of the triphasic velocity waveforms at several segments along
      the femoral and popliteal arteries. Additionally, time-resolved flow velocity was
      quantified in five healthy subjects and compared against gated phase contrast-MRI
      results. To illustrate clinical feasibility, the proposed method was shown to be
      able to identify hemodynamic abnormalities and impaired reactivity in a diseased
      femoral artery. For both phantom and in vivo studies, velocity measurements were
      within 1.5 cm/s, and the coefficient of variation was less than 5% in an in vivo
      reproducibility study. In five healthy subjects, the average differences in mean
      peak velocities and their temporal locations were within 1 cm/s and 10 ms
      compared to gated phase contrast-MRI. In conclusion, the proposed method provides
      temporally resolved arterial velocity with a temporal resolution of 20 ms with
      minimal post processing.

PMID- 20677237
TI  - Motion correction in MR thermometry of abdominal organs: a comparison of the
      referenceless vs. the multibaseline approach.
AB  - Reliable temperature and thermal-dose measurements using proton resonance
      frequency shift-based magnetic resonance (MR) thermometry for MR-guided ablation
      of abdominal organs require a robust correction of artefacts induced by the
      target displacement through an inhomogeneous and time-variant magnetic field. Two
      correction approaches emerged recently as promising candidates to allow
      continuous real-time MR-thermometry under free-breathing conditions: The
      multibaseline correction method, which relies on a pre-recorded correction table
      allowing to correct for periodic phase changes, and the referenceless method,
      which depends on a background phase estimation in the target area based on the
      assumption of a smooth spatial variation of the phase across the organ. This
      study combines both methods with real-time in-plane motion correction to permit
      both temperature and thermal-dose calculations on the fly. Subsequently, the
      practical aspects of both methods are compared in two application scenarios, a
      radio frequency-ablation and a high-intensity focused ultrasound ablation. A
      hybrid approach is presented that exploits the strong points of both methods,
      allowing accurate and precise proton resonance frequency-thermometry measurements
      during periodical displacement, even in the presence of spontaneous motion and
      strong susceptibility variations in the target area.

PMID- 20677236
TI  - Rotating frame spin lattice relaxation in a swine model of chronic, left
      ventricular myocardial infarction.
AB  - T1rho relaxation times were quantified in a swine model of chronic, left
      ventricular myocardial infarction. It was found that there were low frequency
      relaxation mechanisms that suppress endogenous contrast at low spin-lock
      amplitudes and in T2-weighted images. A moderate amplitude spin-locking pulse
      could overcome these relaxation mechanisms. Relaxation dispersion data were
      measured over a range of RF field amplitudes, and a model was formulated to
      include dipole-dipole relaxation modulated by molecular rotation and an apparent
      exchange mechanism. These techniques may find some use in the clinic for the
      observation of chronic, left ventricular cardiac remodeling.

PMID- 20677238
TI  - Single-cell monitoring using fiberoptic nanosensors.
AB  - This article is a review on the design, fabrication, and applications of
      fiberoptic nanosensors for in vivo monitoring of individual living cells. The
      nanosensors were fabricated with tapered optical fibers with distal ends having
      nanometer-sized diameters. Bioreceptors, such as antibody, peptides, and nucleic
      acids, are immobilized on the fiber tips and designed to be selective to target
      analyte molecules of interest. A laser beam is transmitted into the fiber,
      producing an evanescent field at the tip of the nanofiber that is used to excite
      target molecules bound to the bioreceptor molecules. The fluorescence originated
      from the analyte molecules is detected by a photo-detection system. The
      advantages and limitations of nanosensors in providing minimally invasive tools
      to probe subcellular compartments inside individual living cells for health
      effect studies and medical applications are discussed in detail.

PMID- 20677240
TI  - Calculating the frequency of serious reportable adverse events and hospital
      acquired conditions.
AB  - The Centers for Medicare and Medicaid Services (CMS) mandated that Medicare
      Advantage Organizations (MAOs) begin reporting the number of serious reportable
      adverse events and hospital-acquired conditions received on Medicare claims.
      There are additional state mandates and health insurance plan requirements. The
      author provides an analysis of the reporting methodology and proposes an
      alternative approach using rate-based formulas that would yield information that
      is more useful.

PMID- 20677241
TI  - Communication and documentation of preliminary and final radiology reports.
AB  - The "wet-read" consultation has been defined as a rapid response to a clinical
      question posed by a physician to a radiologist. These preliminary interpretations
      are often not well documented, have poor fidelity, and are subject to
      modifications and revisions. Moreover, preliminary interpretations may be subject
      to reinterpretation through a variety of scenarios. Recent technological advances
      in radiology have further hindered the ability to harmonize differences between
      preliminary and final interpretations and communicate these differences to
      treating physicians. High-fidelity simulation may represent a risk management
      strategy aimed at bridging the gap between radiology and communication
      technology.

PMID- 20677242
TI  - Substance abuse and the impaired provider.
AB  - Physicians have a similar rate of substance abuse as the general population,
      though their choice of substance may tend to be different. The impact on the
      physician and his or her patients seriously compromises the delivery of safe and
      effective medical care. This article reviews our knowledge base regarding the
      physician with substance abuse issues and presents a methodology to assist in
      mitigating the risks presented to the provider and patients.

PMID- 20677243
TI  - Understanding the connection between risk appetite and risk analytics.
AB  - A clear articulation of an organization's risk appetite and sound, objective
      analytics are essential for ongoing risk management performance measurement,
      which is crucial to ultimate risk management success and, ultimately, achieving
      the organization's strategic objectives. This article explores the risk
      management process as a cycle of appetite and analytics that can help clear the
      way to better risk assessment and management.

PMID- 20677244
TI  - Complaints, grievances, and claims against physicians: does tort reform make a
      difference?
AB  - This study reviews data available from a mediation committee (MC) for a county
      medical society, the Texas Medical Board (TMB), and the Texas Medical Liability
      Trust (TMLT) during the decade of Texas tort reform. It explores why some
      patients file formal complaints and grievances against their physicians. It also
      compares data from the TMB and TMLT to investigate how tort reform might
      influence their activities. Results show the majority of complaints or grievances
      mediated by the MC start with communication problems followed by allegations of
      inappropriate treatment, fees, medical records, and delays in diagnoses. Analysis
      of available data also suggests changes in liability rules may reduce liability
      claims while having little or no impact on mediated case trends or their triggers
      at least to one county medical society.

PMID- 20677245
TI  - General liability: transporting patient for discharge gives rise to general
      liability claim. Hill v Wadsworth-Rittman Hospital, C. A. No. 09CA0012-M (Ohio
      App., October 13, 2009).

PMID- 20677249
TI  - Ultrafast imaging: principles, pitfalls, solutions, and applications.
AB  - Ultrafast MRI refers to efficient scan techniques that use a high percentage of
      the scan time for data acquisition. Often, they are used to achieve short scan
      duration ranging from sub-second to several seconds. Alternatively, they may form
      basic components of longer scans that may be more robust or have higher image
      quality. Several important applications use ultrafast imaging, including real
      time dynamic imaging, myocardial perfusion imaging, high-resolution coronary
      imaging, functional neuroimaging, diffusion imaging, and whole-body scanning.
      Over the years, echo-planar imaging (EPI) and spiral imaging have been the main
      ultrafast techniques, and they will be the focus of the review. In practice,
      there are important challenges with these techniques, as it is easy to push
      imaging speed too far, resulting in images of a nondiagnostic quality. Thus, it
      is important to understand and balance the trade-off between speed and image
      quality. The purpose of this review is to describe how ultrafast imaging works,
      the potential pitfalls, current solutions to overcome the challenges, and the key
      applications.

PMID- 20677250
TI  - Glioma morphology and tumor-induced vascular alterations revealed in seven rodent
      glioma models by in vivo magnetic resonance imaging and angiography.
AB  - PURPOSE: To evaluate the added value of non-contrast-enhanced MR angiography
      (MRA) to conventional MR imaging for a detailed characterization of different
      rodent glioma models. MATERIALS AND METHODS: Intracerebral tumor cell
      implantation and chemical induction methods were implemented to obtain rat C6,
      9L/LacZ, F98, RG2, and ethyl-nitrosourea (ENU) -induced glioma models, a human
      U87 MG tumor model as well as a mouse GL261 glioma model. MR assessments were
      regularly conducted on a 7 Tesla Bruker BioSpin system. The tumor border
      sharpness and growth characteristics of each glioma model were assessed from T(2)
      weighted images. Neovascularization and vascular alterations inherent to each
      model were characterized by assessing absolute blood volumes, vessel density,
      length, and diameter using Mathematica and Amira software. RESULTS: The 9L/LacZ
      and ENU gliomas both presented flaws that hinder their use as reliable brain
      tumor models. C6 gliomas were slightly invasive and induced moderate vascular
      alterations, whereas GL261 tumors dramatically altered the brain vessels in the
      glioma region. F98, RG2, and U87 are infiltrative models that produced dramatic
      vascular alterations. CONCLUSION: MRI and MRA provided crucial in vivo
      information to identify a distinctive "fingerprint" for each of our seven rodent
      glioma models.

PMID- 20677251
TI  - Interindividual, repositioning, and time-of-day effects on single voxel proton MR
      spectroscopy of the anterior cingulate cortex.
AB  - PURPOSE: To measure interindividual, repositioning, and time-of-day effects of
      single voxel PRESS (Point RESolved Spectroscopy) proton magnetic resonance
      spectroscopy ((1)H-MRS) acquisition of the anterior cingulate cortex (AC) in
      healthy human subjects. MATERIALS AND METHODS: AC (1)H-MRS measurements were
      performed in 15 healthy adult volunteers using a short echo PRESS sequence (GE
      Healthcare 3 Tesla, TE/TR = 30/2500 ms, 192 acquisitions, 6 cm(3) voxels). For
      each individual, a total of eight spectra were obtained during two identical
      scanning sessions separated by 3.5 h. In each, two consecutive AC spectra were
      acquired. After the first two scans, the subject left the scanner, then
      immediately returned for repositioning and acquisition of two more consecutive
      spectra. The subject then left the imaging centre to return 3.5 h later for a
      repeated procedure. Spectroscopic postprocessing was done using LCmodel.
      Interindividual, repositioning and time-of-day effects were measured using
      restricted maximum likelihood (REML) models of variance components analysis,
      where response variables were levels of creatine/phosphocreatine (Cr), N-acetyl
      aspartate (NAA), myo-inositol (mI), choline (Cho), and the glutamate-glutamine
      complex (Glx). RESULTS: Interindividual effects were markedly higher than time-of
      day and repositioning effects for all metabolites. CONCLUSION: Our findings show
      that (1)H-MRS measurements of the AC are sensitive to interindividual
      differences, while time of day and repositioning are markedly less important.

PMID- 20677252
TI  - Perfusion MRI in neuro-psychiatric systemic lupus erthemathosus.
AB  - PURPOSE: To use perfusion weighted MR to quantify any perfusion abnormalities and
      to determine their contribution to neuropsychiatric (NP) involvement in systemic
      lupus erythematosus (SLE). MATERIALS AND METHODS: We applied dynamic
      susceptibility contrast (DSC) perfusion MRI in 15 active NPSLE, 26 inactive NPSLE
      patients, and 11 control subjects. Cerebral blood flow (CBF), cerebral blood
      volume (CBV), and mean transit time (MTT) maps were reconstructed and regions of
      interest were compared between groups. In addition, the effect of SLE criteria,
      NPSLE syndromes, immunological coagulation disorder, and medication on CBF, CBV,
      and MTT was investigated. RESULTS: No significant differences were found between
      the groups in CBF, CBV, and MTT. No significant influence of SLE criteria or
      NPSLE syndromes on CBF, CBV, or MTT was found. No significant influence of anti
      cardiolipin antibodies, lupus anti-coagulant, the presence of anti-phospholipid
      syndrome (APS), or medication on CBF, CBV, or MTT was found. CONCLUSION: Our
      findings suggest CBF, CBV, and MTT in the white and the gray matter in SLE
      patients is not significantly different from healthy controls or between patients
      with and without specific symptoms or with and without immunological disorder
      involving coagulation.

PMID- 20677253
TI  - Filtered deconvolution of a simulated and an in vivo phase model of the human
      brain.
AB  - PURPOSE: To remove spatial patterns in gradient echo phase images which are
      caused by susceptibility differences between different tissue types using
      filtered deconvolution and to evaluate deconvolution effects. MATERIALS AND
      METHODS: A realistic simulated susceptibility map of the human brain was built
      and used to evaluate the effects of filtered deconvolution. The simulated
      susceptibility map was convolved with a filter kernel representing a magnetic
      dipole resulting in a simulated phase map. The artificial phase map was
      superimposed with different noise levels and deconvolved using different
      deconvolution kernels. The resulting contrast-to-noise ratios between white and
      gray matter of the deconvolved data provide an estimate for an optimal
      deconvolution kernel for a given noise level. These results were used to
      deconvolve an in vivo phase model representing the average of 30 phase data sets
      and also individual phase data acquired at 7 Tesla. RESULTS: The deconvolved
      phase model shows a better anatomical agreement with the corresponding magnitude
      than the original phase model (5% higher kappa coefficient). Visual inspection of
      the deconvolved individual phase shows a more consistent delineation of blood
      vessels. CONCLUSION: Filtered deconvolution of SWI phase is possible when an
      appropriate filter kernel is used. This helps to improve region of interest
      definition as unrealistic phase patterns are removed.

PMID- 20677254
TI  - Evaluation of group homogeneity during acupuncture stimulation in fMRI studies.
AB  - PURPOSE: To evaluate the extent of individual differences of functional MRI
      (fMRI) signal changes induced by acupuncture stimulation. MATERIALS AND METHODS:
      Acupuncture at ST36 and checkerboard stimulation was applied to 16 subjects. We
      calculated the mean distance using beta values in a generalized linear model
      (GLM) analysis and employed it to study the group homogeneity by detecting the
      outliers. RESULTS: A more significant individual difference was presented in
      acupuncture stimulation compared with visual stimulation through evaluation of
      the mean distance. From the group results, we found that the activations were
      more significant in the homogeneous group results. Combining the behavior and
      fMRI results, there was no direct correlation between deqi index and mean
      distance in acupuncture stimulation. The deqi index of the outlier was in the
      normal range and did not differ significantly from others. CONCLUSION:
      Traditional group results without removing outliers were not sensitive enough to
      detect the real acupuncture effect. We suggest that individual difference should
      be taken into consideration for future acupuncture studies. Also, group analysis
      paralleled with individual analysis is critical for a full understanding of
      acupuncture effects.

PMID- 20677255
TI  - Neurovascular changes measured by time-of-flight MR angiography in cholesterol
      fed rabbits with cortical amyloid beta-peptide accumulation.
AB  - PURPOSE: To test the hypothesis that narrowing of cranial blood vessels in
      cholesterol-fed rabbits is a function of the duration of the high cholesterol
      diet. Such neurovascular changes, caused by elevated serum cholesterol, are
      linked to stroke and Alzheimer's disease risk. MATERIALS AND METHODS: Four groups
      of New Zealand White rabbits were studied. Six were fed a normal diet, 19 were
      fed a 2% cholesterol diet with 0.12 ppm copper in the drinking water for 8 weeks,
      10 weeks, or 12 weeks. Time-of-flight (TOF) MR angiography (MRA) at 3 Tesla was
      used to measure arterial diameters in 11 vessels. Previously published data for
      amyloid beta-peptide (Abeta) accumulation in the brains measured postmortem were
      correlated to vessel diameters. Ventricular volumes of rabbits were measured on
      group-averaged data. RESULTS: Several vessel diameters decreased with cholesterol
      diet duration. The posterior communicating arteries showed the largest
      significant effect. Abeta accumulation was inversely correlated with arterial
      diameter. Ventricular volumes between the normal diet and 12 weeks cholesterol
      fed groups were not significantly different. CONCLUSION: Reduction in vessel
      diameter of medium-sized vessels but not large vessels was measured in these
      hypercholesterolemic rabbits. The vessel diameter narrowing and cortical Abeta
      deposition occurred before measurable ventricular enlargement.

PMID- 20677256
TI  - International reproducibility of single breathhold T2* MR for cardiac and liver
      iron assessment among five thalassemia centers.
AB  - PURPOSE: To examine the reproducibility of the single breathhold T2* technique
      from different scanners, after installation of standard methodology in five
      international centers. MATERIALS AND METHODS: Up to 10 patients from each center
      were scanned twice locally for local interstudy reproducibility of heart and
      liver T2*, and then flown to a central MR facility to be rescanned on a reference
      scanner for intercenter reproducibility. Interobserver reproducibility for all
      scans was also assessed. RESULTS: Of the 49 patients scanned, the intercenter
      reproducibility for T2* was 5.9% for the heart and 5.8% for the liver. Local
      interstudy reproducibility for T2* was 7.4% for the heart and 4.6% for the liver.
      Interobserver reproducibility for T2* was 5.4% for the heart and 4.4% for the
      liver. CONCLUSION: These data indicate that T2* MR may be developed into a
      widespread test for tissue siderosis providing that well-defined and approved
      imaging and analysis techniques are used.

PMID- 20677257
TI  - Edited MRS is sensitive to changes in lactate concentration during inspiratory
      hypoxia.
AB  - PURPOSE: To demonstrate the application of Mescher-Garwood (MEGA) point-resolved
      spectroscopy sequence (PRESS) editing to the detection of lactate in the brain at
      3T and to investigate changes in lactate concentration associated with
      inspiratory gas challenges. MATERIALS AND METHODS: Edited lactate measurements
      were made in six healthy volunteers while the subjects breathed normoxic (21%
      O(2)), hypoxic (12% O(2)), and hyperoxic (40% O(2)) gas mixtures. Lactate
      concentration was quantified relative to the unsuppressed water signal from the
      same volume. RESULTS: Lactate concentration was elevated in all subjects during
      hypoxia in a highly significant fashion (mean increase = 39%; P = 0.0003). There
      was no significant change seen in hyperoxia. CONCLUSION: MEGA-PRESS editing at 3T
      is sufficiently sensitive to detect lactate in the healthy brain with good signal
      to-noise ratio (SNR), and can be used to investigate changes in cerebral
      metabolism arising during inspiratory gas challenges.

PMID- 20677258
TI  - Ultra-short echo time (UTE) MR imaging of the lung: comparison between normal and
      emphysematous lungs in mutant mice.
AB  - PURPOSE: To investigate the utility of ultra-short echo time (UTE) sequence as
      pulmonary MRI to detect non-uniform disruption of lung architecture that is
      typical of emphysema. MATERIALS AND METHODS: MRI of the lungs was conducted with
      a three-dimensional UTE sequence in transgenic mice with severe emphysema and
      their wild-type littermates in a 3 Tesla clinical MR system. Measurements of the
      signal intensity (SI) and transverse relaxation time (T2*) of the lung parenchyma
      were performed with various echo times (TEs) ranging from 100 micros to 2 ms.
      RESULTS: Much higher SI of the lung parenchyma was observed at an UTE of 100
      micros compared with longer TEs. The emphysematous lungs had reduced SIs and T2*
      than the controls, in particular at end-expiratory phase. The results suggested
      that both SI and T2* in lung parenchyma measured with the method represent
      fractional volume of lung tissue. CONCLUSION: The UTE imaging provided MR signal
      from the lung parenchyma. Moreover, the UTE sequence was sensitive to
      emphysematous changes and may provide a direct assessment of lung parenchyma. UTE
      imaging has the potential to assist detection of localized pathological
      destruction of lung tissue architecture in emphysema.

PMID- 20677259
TI  - Can MR fluoroscopic triggering technique and slow rate injection provide
      appropriate arterial phase images with reducing artifacts on gadoxetic acid-DTPA
      (Gd-EOB-DTPA)-enhanced hepatic MR imaging?
AB  - PURPOSE: To evaluate whether using MR fluoroscopic triggering technique and slow
      rate injection improves the quality of arterial phase images in gadoxetic acid
      DTPA-enhanced (Gd-EOB-DTPA) MR imaging because of proper acquisition timing and
      reduction of artifacts. MATERIALS AND METHODS: Two hundred sixteen patients
      undergoing examination for liver diseases were retrospectively reviewed. All MR
      images were obtained with two Gd-EOB-DTPA injection protocols: (i) a combination
      protocol, in which the MR fluoroscopic triggering technique and slow rate
      injection (1 mL/s) were used; and for comparison, (ii) a conventional protocol,
      in which adjusted fixed scan delay and ordinary rate injection (2 mL/s) were
      adopted. Signal-to-noise ratio (SNR) of aorta, portal vein, and liver parenchyma
      on arterial phase images were calculated. Two blinded readers independently
      evaluated the obtained arterial phase images in terms of acquisition timing and
      degree of artifacts. RESULTS: The SNRs of aorta and portal vein on arterial phase
      images were significantly higher in the combination protocol group (aorta/portal:
      221.9 +/- 91.9/197.1 +/- 89.8) than that in the conventional protocol group
      (aorta/portal: 169.8 +/- 97.4/92.7 +/- 48.5) (P < 0.05). The acquisition timing
      for arterial phase images with the combination protocol was significantly better
      than that with the conventional protocol (P < 0.01). The image quality of the
      combination protocol was significantly higher than that of the conventional
      protocol (P < 0.01). The occurrence rate of moderate or severe degree of
      artifacts in the conventional protocol (38.0%) was more prominent than that in
      the combination protocol (18.5%). CONCLUSION: The combination of the MR
      fluoroscopic triggering technique and slow rate injection provides proper
      arterial phase images and reduces the artifacts in Gd-EOB-DTPA MR imaging.

PMID- 20677260
TI  - Focal nodular hyperplasia: central scar enhancement pattern using Gadoxetate
      Disodium.
AB  - PURPOSE: To illustrate the unusual enhancement pattern of the focal nodular
      hyperplasia central scar using Gadoxetate Disodium. MATERIALS AND METHODS: Over a
      10-month period, six patients, with a total of seven focal nodular hyperplasia
      lesions with typical central scar, had MRI of the liver using Gadoxetate Disodium
      (Eovist, Bayer HealthCare Pharmaceuticals Inc., Wayne, NJ). Four of the six
      patients had a prior Gadobenate Dimeglumine (Multihance, Bracco Diagnostics Inc.,
      Princeton, NJ) -enhanced MRI of the liver performed within the previous year. The
      dynamic enhancement pattern of the central scar on the 10 liver MRIs was
      independently analyzed by two abdominal imaging radiologists who were blinded to
      the contrast agent used. RESULTS: On the Gadoxetate Disodium-enhanced MRIs and
      during the arterial phase, 1-min, 2-min, and 3-min delay, none of the central
      scars demonstrated enhancement. However, all four of the lesions that were
      previously scanned using Gadobenate Dimeglumine demonstrated typical enhancement
      after a 3-min delay. CONCLUSION: On Gadoxetate Disodium-enhanced MRIs of the
      liver, the central scar of focal nodular hyperplasia lesions does not typically
      demonstrate delayed enhancement.

PMID- 20677261
TI  - Feasibility of small bowel flow rate measurement with MRI.
AB  - OBJECTIVE: To evaluate whether it is feasible to measure the segmental flux of
      small bowel content using MR phase-contrast (PC) pulse sequences. MATERIALS AND
      METHODS: Using a phantom the accuracy of flux measurements was validated.
      Afterwards, 10 volunteers were included in a prospective clinical trial. To
      provide standardized small bowel distension, all volunteers ingested four equal
      portions of 400 mL of water doped with 5 mL gadoterate and 5.8 g Metamucil mite.
      The MR protocol covering the sagittal cross-sections of the small bowel included
      several two-dimensional (2D) PC sequences with a velocity encoding of 7 cm/second
      at a temporal resolution of 0.55 second. As proof of concept time-dependent flux
      was measured after intravenous (i.v.) administration of a spasmolytic agent in
      one volunteer. RESULTS: Phantom measurements resulted in an excellent correlation
      between pump and PC measured flow rates (R = 0.999). Time-resolved small bowel
      flux was successfully measured in distended small bowel loops of all volunteers.
      A mean flow rate of 0.188 mL/second (standard deviation +/- 0.144 mL/second) was
      documented. The flux plots presented a sinus wave-like shape with regular aboral
      and oral flow. A spasmolytic effect both on flux and motility could be shown with
      residual flux despite complete arrest of small bowel motility. CONCLUSION: PC MRI
      allows time-resolved in vivo measurement of small bowel flux in single well
      distended bowel loops filled with gadolinium-doped aqueous solution.

PMID- 20677262
TI  - Texture-based classification of focal liver lesions on MRI at 3.0 Tesla: a
      feasibility study in cysts and hemangiomas.
AB  - PURPOSE: To determine the feasibility of texture analysis for the classification
      of liver cysts and hemangiomas, on nonenhanced, zero-fill interpolated T1- and T2
      weighted MR images. MATERIALS AND METHODS: Forty-five patients (26 women and 19
      men; mean age, 58.1 +/- 16.9 years) with liver cysts or hemangiomas were enrolled
      in the study. After exclusion of images with artifacts, T1-weighted images of 42
      patients, and T2-weighted images of 39 patients, obtained at 3.0 Tesla (T), were
      available for further analysis. Texture features derived from the gray-level
      histogram, co-occurrence and run-length matrix, gradient, autoregressive model,
      and wavelet transform were calculated. Fisher, probability of classification
      error and average correlation (POE+ACC), and mutual information coefficients were
      used to extract subsets of optimized texture features. Linear discriminant
      analysis (LDA) in combination with k nearest neighbor (k-NN) classification, and
      k-means clustering, were used for lesion classification. RESULTS: LDA/k-NN
      produced misclassification rates of 16-18% on T1-weighted, and 12-18% on T2
      weighted images. K-means clustering yielded misclassification rates of 15-23% on
      T1-weighted, and 15-25% on T2-weighted images. CONCLUSION: Texture-based
      classification of liver cysts and hemangiomas is feasible on zero-fill
      interpolated MR images obtained at 3.0T. Further studies are warranted to
      investigate the value of texture-based classification of other liver lesions,
      such as hepatocellular and cholangiocellular carcinoma, on MRI.

PMID- 20677263
TI  - Value of delayed hypointensity and delayed enhancing rim in magnetic resonance
      imaging diagnosis of small hepatocellular carcinoma in the cirrhotic liver.
AB  - PURPOSE: To determine the diagnostic utility of delayed hypointensity and delayed
      enhancing rim on magnetic resonance imaging (MRI) as indicators of hepatocellular
      carcinoma (HCC) in arterially enhancing nodules < or =5 cm in the cirrhotic liver
      and determine the features that best predict HCC. MATERIALS AND METHODS:
      Gadolinium-enhanced MRI studies performed from January 2001 to December 2004 in
      patients with cirrhosis were evaluated for arterially enhancing nodules measuring
      < or =5 cm. Verification was via explant correlation, biopsy, or imaging follow
      up. Sensitivity and specificity of diagnostic features of HCC were calculated.
      Features predictive of HCC were determined using the Generalized Estimating
      Equation approach. RESULTS: In all, 116 arterially enhancing nodules were
      identified in 80 patients (<2 cm: n = 79, 2-5 cm n = 37). Sensitivity and
      specificity of delayed hypointensity for HCC measuring < or =5 cm, 2-5 cm, and <2
      cm were 0.54 (40 of 74) and 0.86 (36 of 42); 0.72 (23 of 32) and 0.80 (4 of 5);
      and 0.41 (17 of 42) and 0.87 (32 of 37). For the delayed enhancing rim
      sensitivity and specificity were 0.64 (47 of 74) and 0.86 (36 of 42); 0.75 (24 of
      32) and 1.0 (5 of 5); and 0.55 (23 of 42) and 0.83 (31 of 37), respectively.
      Lesion size (> or =2 cm) and delayed enhancing rim, as main features and their
      interaction, were the most significant predictors of HCC. CONCLUSION: Delayed
      hypointensity and enhancing rim improve the specificity of diagnosis of HCC of
      all sizes but are seen less frequently in small (<2 cm) HCC. Nodule size (> or =2
      cm) and delayed enhancing rim are the strongest predictors of HCC.

PMID- 20677265
TI  - The influence of the b-value combination on apparent diffusion coefficient based
      differentiation between malignant and benign tissue in cervical cancer.
AB  - PURPOSE: To analyze the influence of different b-value combinations on apparent
      diffusion coefficient (ADC)-based differentiation of known malignant and benign
      tissue in cervical cancer patients. MATERIALS AND METHODS: A total of 35 patients
      with stage IB1, IB2, IIA cervical cancer underwent a 3.0T MRI scan prior to
      radical hysterectomy and pelvic lymph node dissection. Conventional T1- and T2
      weighted sequences and a diffusion-weighted sequence (b = 0, 150, 500, 1000
      seconds/mm(2)) were performed. Regions-of-interest (ROI) were drawn on ADC maps
      derived from five different b-value combinations (0, 500; 0, 150, 500; 0, 1000;
      0, 150, 500, 1000; 150, 500, 1000 seconds/mm(2)). The influence of the b-value
      combination on ADC-based differentiation of benign and malignant tissue was
      analyzed using receiver-operating-characteristics curves. RESULTS: For all b
      value combinations, ADCs were significantly lower (P < 0.001) in cervical
      malignancies (1.15 +/- 0.21.10(-3); 1.10 +/- 0.21.10(-3); 0.97 +/- 0.18.10(-3);
      0.97 +/- 0.23.10(-3) and 0.85 +/- 0.18.10(-3) mm(2)/second respectively to the
      aforementioned b-value combinations) than in benign cervix (2.08 +/- 0.31.10(-3);
      2.00 +/- 0.29.10(-3); 1.62 +/- 0.23.10(-3); 1.54 +/- 0.21.10(-3) and 1.42 +/-
      0.22.10(-3) mm(2)/second respectively). The diagnostic accuracy was high for all
      b-value combinations and without statistical differences between the
      combinations. CONCLUSION: ADC-based differentiation of benign from malignant
      cervical tissue is independent of the tested b-value combinations. The results
      support the inclusion and possible pooling of studies using different b-value
      combinations in meta-analyses on ADC-based tissue differentiation in cervical
      cancer.

PMID- 20677264
TI  - MRI of iron-oxide labelled transplanted hepatocytes in mice: effect of treatment
      with cyclophosphamide.
AB  - PURPOSE: To assess if 1.5T MRI can be used to study the transport to the liver,
      the intrahepatic distribution and engraftment of iron-oxide labelled hepatocytes
      in cyclophosphamide-treated and untreated mice. MATERIALS AND METHODS:
      Hepatocytes were isolated from C57bl/6 mice and were labelled with 1.63 microm
      iron-oxide particles. Seventeen mice were pretreated with cyclophosphamide to
      disrupt the sinusoidal endothelium and 15 were left untreated. Seven days after
      splenic injection of the labelled hepatocytes, T2*-weighted gradient-echo images
      at 1.5T were acquired. The hepatic transport, distribution and engraftment of the
      labelled hepatocytes were assessed with signal intensity (SI) and T2*
      measurements, electron paramagnetic resonance (EPR), texture analysis and
      histology. RESULTS: Lower hepatic SI (P = 0.005), lower T2* (P = 0.033) and
      larger number of particles at histology (P = 0.006) suggested increased transport
      to the liver of labelled hepatocytes in cyclophosphamide-treated mice versus
      untreated mice. At histology, most particles were located in Kupffer cells.
      Particles distribution was heterogeneous. No difference between both groups was
      observed at texture analysis. CONCLUSION: MRI is useful to assess the transport
      to the liver and intrahepatic distribution of transplanted labelled hepatocytes.
      The preferential location of iron-oxide particles within Kupffer cells after
      seven days limits the value of MRI for assessing hepatocyte engraftment.

PMID- 20677266
TI  - Intra-renal oxygenation in rat kidneys during water loading: effects of
      cyclooxygenase (COX) inhibition and nitric oxide (NO) donation.
AB  - PURPOSE: To evaluate intra-renal oxygenation by blood oxygenation level dependent
      (BOLD) MRI in rat kidneys during water loading and to investigate if the NO
      donating moiety in naproxcinod could compensate for the effect of cyclooxygenase
      (COX) inhibition of naproxen. MATERIALS AND METHODS: Nineteen male Sprague Dawley
      rats were divided into three groups and dosed with vehicle, naproxen or
      naproxcinod by gavage for two weeks. On the day of the experiment, hypotonic
      saline with glucose was infused intravenously to induce water diuresis. BOLD MRI
      data to monitor renal oxygenation and timed urine samples for estimation of
      prostaglandins (PGs) and urine flow were obtained. RESULTS: The data in this
      study is consistent with previous experience in humans in that pre-treatment with
      naproxen abolished the improvement in medullary oxygenation during water loading.
      In addition, the inhibition of PGs by naproxcinod reached similar levels as
      naproxen but maintained the improvement in oxygenation in renal medulla during
      water loading. CONCLUSION: This suggests that naproxcinod may have less
      nephrotoxicity and that the NO donating moiety partially compensates for the
      hemodynamic effects of prostaglandin inhibition by naproxen.

PMID- 20677267
TI  - Comparison of 3.0 T proton magnetic resonance spectroscopy short and long echo
      time measures of intramyocellular lipids in obese and normal-weight women.
AB  - PURPOSE: To compare correlations of intramyocellular lipids (IMCL) measured by
      short and long echo-time proton magnetic resonance spectroscopy (1H-MRS) with
      indices of body composition and insulin resistance in obese and normal-weight
      women. MATERIALS AND METHODS: We quantified IMCL of tibialis anterior (TA) and
      soleus (SOL) muscles in 52 premenopausal women (37 obese and 15 normal weight)
      using single-voxel 1H-MRS PRESS at 3.0 T with short (30 msec) and long (144 msec)
      echo times. Statistical analyses were performed to determine correlations of IMCL
      with body composition as determined by computed tomography (CT) and insulin
      resistance indices and to compare correlation coefficients from short and long
      echo-time data. Signal-to-noise ratio (SNR), linewidth, and coefficients of
      variation (CV) of short and long echo-time spectra were calculated. RESULTS:
      Short and long echo-time IMCL from TA and SOL significantly correlated with body
      mass index (BMI) and abdominal fat depots (r = 0.32 to 0.70, P = <0.05), liver
      density (r = -0.39 to -0.50, P < 0.05), and glucose area under the curve as a
      measure of insulin resistance (r = 0.47 to 0.49, P < 0.05). There was no
      significant difference between correlation coefficients of short and long echo
      time spectra (P > 0.5). Short echo-time IMCL in both muscles showed significantly
      higher SNR (P < 0.0001) and lower CVs when compared to long echo-time
      acquisitions. Linewidth measures were not significantly different between groups.
      CONCLUSION: IMCL quantification using short and long echo-time 1H-MRS at 3.0 T is
      useful to detect differences in muscle lipid content in obese and normal-weight
      subjects. In addition, IMCL correlates with body composition and markers of
      insulin resistance in this population with no significant difference in
      correlations between short and long echo-times. Short echo-time IMCL
      quantification of TA and SOL muscles at 3.0 T was superior to long echo-time due
      to better SNR and better reproducibility.

PMID- 20677268
TI  - Impact of motion on T1 mapping acquired with inversion recovery fast spin echo
      and rapid spoiled gradient recalled-echo pulse sequences for delayed gadolinium
      enhanced MRI of cartilage (dGEMRIC) in volunteers.
AB  - PURPOSE: To evaluate the impact of motion on T1 values acquired by using either
      inversion-recovery fast spin echo (IR-FSE) or three-dimensional (3D) spoiled
      gradient recalled-echo (SPGR) sequences for delayed gadolinium-enhanced magnetic
      resonance imaging of cartilage (dGEMRIC) in volunteers. MATERIALS AND METHODS:
      Single-slice IR-FSE and 3D SPGR sequences were applied to perform dGEMRIC in five
      healthy volunteers. A mutual information-based approach was used to correct for
      image misregistration. Displacements were expressed as averaged Euclidean
      distances and angles. Averages of differences in goodness of fit (Deltachi(2))
      tests and averages of relative differences in T1 values (DeltaT1) before and
      after motion correction were computed. RESULTS: Maximum Euclidean distance was
      3.5 mm and 1.2 mm for IR-FSE and SPGR respectively. Mean +/- SD of Deltachi(2)
      were 10.18 +/- 8.4 for IR-FSE and -1.37 +/- 5.5 for SPGR. Mean +/- SD of DeltaT1
      were 0.008 +/- 0.0048 for IR-FSE and -0.002 +/- 0.019 for FSPGR. Pairwise
      comparison of Deltachi(2) values showed a significant difference for IR-FSE, but
      not for 3D-SPGR. Significantly greater variability in T1 values was also noted
      for IR-FSE than for 3D-SPGR. CONCLUSION: Involuntary motion has a significant
      influence on T1 values acquired with IR-FSE, but not with 3D-SPGR in healthy
      volunteers.

PMID- 20677269
TI  - 3D flow-independent peripheral vessel wall imaging using T(2)-prepared phase
      sensitive inversion-recovery steady-state free precession.
AB  - PURPOSE: To develop a 3D flow-independent peripheral vessel wall imaging method
      using T(2)-prepared phase-sensitive inversion-recovery (T(2)PSIR) steady-state
      free precession (SSFP). MATERIALS AND METHODS: A 3D T(2)-prepared and
      nonselective inversion-recovery SSFP sequence was designed to achieve flow
      independent blood suppression for vessel wall imaging based on T(1) and T(2)
      properties of the vessel wall and blood. To maximize image contrast and reduce
      its dependence on the inversion time (TI), phase-sensitive reconstruction was
      used to restore the true signal difference between vessel wall and blood. The
      feasibility of this technique for peripheral artery wall imaging was tested in 13
      healthy subjects. Image signal-to-noise ratio (SNR), wall/lumen contrast-to-noise
      ratio (CNR), and scan efficiency were compared between this technique and
      conventional 2D double inversion recovery - turbo spin echo (DIR-TSE) in eight
      subjects. RESULTS: 3D T(2)PSIR SSFP provided more efficient data acquisition (32
      slices and 64 mm in 4 minutes, 7.5 seconds per slice) than 2D DIR-TSE (2-3
      minutes per slice). SNR of the vessel wall and CNR between vessel wall and lumen
      were significantly increased as compared to those of DIR-TSE (P < 0.001). Vessel
      wall and lumen areas of the two techniques are strongly correlated (intraclass
      correlation coefficients: 0.975 and 0.937, respectively; P < 0.001 for both). The
      lumen area of T(2)PSIR SSFP is slightly larger than that of DIR-TSE (P = 0.008).
      The difference in vessel wall area between the two techniques is not
      statistically significant. CONCLUSION: T(2)PSIR SSFP is a promising technique for
      peripheral vessel wall imaging. It provides excellent blood signal suppression
      and vessel wall/lumen contrast. It can cover a 3D volume efficiently and is flow-
      and TI-independent.

PMID- 20677270
TI  - Diffusion-weighted MRI for monitoring tumor response to photodynamic therapy.
AB  - PURPOSE: To examine diffusion-weighted MRI (DW-MRI) for assessing the early tumor
      response to photodynamic therapy (PDT). MATERIALS AND METHODS: Subcutaneous tumor
      xenografts of human prostate cancer cells (CWR22) were initiated in athymic nude
      mice. A second-generation photosensitizer, Pc 4, was delivered to each animal by
      a tail vein injection 48 h before laser illumination. A dedicated high-field (9.4
      Tesla) small animal MR scanner was used to acquire diffusion-weighted MR images
      pre-PDT and 24 h after the treatment. DW-MRI and apparent diffusion coefficients
      (ADC) were analyzed for 24 treated and 5 control mice with photosensitizer only
      or laser light only. Tumor size, prostate specific antigen (PSA) level, and tumor
      histology were obtained at different time points to examine the treatment effect.
      RESULTS: Treated mice showed significant tumor size shrinkage and decrease of PSA
      level within 7 days after the treatment. The average ADC of the 24 treated tumors
      increased 24 h after PDT (P < 0.001) comparing with pre-PDT. The average ADC was
      0.511 +/- 0.119 x 10(-3) mm(2)/s pre-PDT and 0.754 +/- 0.181 x 10(-3) mm(2)/s 24
      h after the PDT. There is no significant difference in ADC values pre-PDT and 24
      h after PDT in the control tumors (P = 0.20). CONCLUSION: The change of tumor ADC
      values measured by DW-MRI may provide a noninvasive imaging marker for monitoring
      tumor response to Pc 4-PDT as early as 24 h.

PMID- 20677271
TI  - Two- and three-dimensional multinuclear stray-field imaging of rotating samples
      with magic-angle spinning (STRAFI-MAS): from bio to inorganic materials.
AB  - PURPOSE: To revisit and illustrate the potential of a simple and effective
      multidimensional stray-field imaging technique with magic-angle spinning, known
      as STRAFI-MAS. MATERIALS AND METHODS: STRAFI-MAS images are acquired with a
      standard NMR magnet and a traditional magic-angle sample spinning (MAS) probe.
      The stray-field gradients are achieved by placing the MAS probe, along the z
      direction, at a distance from the center of the magnet. No pulsed-field gradients
      are applied. The multidimensional spatial encoding is carried out by
      synchronizing the radiofrequency pulses with the sample MAS rotation. RESULTS:
      Two-dimensional (2D) and 3D multinuclear images of various phantoms, including a
      tibia bone and silicon carbide, are recorded. Images of inorganic solids
      containing quadrupolar nuclei, (23)Na and (27)Al, are also explored for the first
      time by STRAFI-MAS. CONCLUSION: We have demonstrated that STRAFI-MAS is a simple
      and user-friendly technique for multidimensional imaging without the need of
      imaging equipment. With the current advancements in NMR and MRI methodologies,
      STRAFI-MAS is expected to be further developed and improved. We anticipate that
      STRAFI-MAS can spark a wide spectrum of interest, from material to bio science,
      where can benefit from high-resolution images.

PMID- 20677272
TI  - Individual voxel-based analysis of brain magnetization transfer maps shows great
      variability of gray matter injury in the first stage of multiple sclerosis.
AB  - In multiple sclerosis (MS), it seems likely that the variability of the long-term
      disability might be partly due to the variability of the early gray matter (GM)
      injury. In the present study, we assessed the variability of GM injury in early
      MS, using a method designed to determine individual pathological GM patterns.
      Eighteen patients presenting with a clinically isolated syndrome and 24 healthy
      matched control subjects were included in this study. Patients were explored
      using a 1.5 Tesla MR scanner (Magnetom Vision Plus; Siemens). Brain MR protocol
      included magnetization transfer ratio imaging (MTR). Statistical mapping analyses
      were performed to compare each subject's GM MTR maps with those of the whole
      group of control subjects (SPM5). The statistical threshold was taken to be the
      maximum P value showing no significant cluster when any control individual was
      compared with the whole control population. GM abnormalities were observed in 83%
      of the patients, ranging in size from 0.3 to 125 cm(3). Among the patients with
      GM abnormalities, 87% had abnormalities located in the temporal cortex, 80% in
      the frontal cortex, 80% in the limbic cortex, 73% in the posterior fossa, 53% in
      the deep GM, 47% in the parietal cortex, and 47% in the occipital cortex.
      Individual statistical mapping of MTR data, which gives a quantitative assessment
      of individual GM lesions, demonstrates great variability of grey matter injury in
      the first stage of multiple sclerosis.

PMID- 20677273
TI  - Effective use of flow-spoiled FBI and time-SLIP methods in the diagnostic study
      of an aberrant vessel of the head and neck: "left jugular venous steal by the
      right jugular vein".
AB  - Three-dimensional (3D) time-of-flight (TOF) is now commonly used in routine
      magnetic resonance angiography (MRA) studies of the head and neck. However, there
      are limits to its diagnostic abilities in the clinical field and, in some
      instances, a more invasive supplementary examination may be required. We
      incidentally discovered a patient with an aberrant vessel of the head and neck
      that ran alongside the left carotid artery and contained a constant, slowly
      pulsating efferent blood flow. 3D-TOF and carotid ultrasonography could not
      determine the nature and origin of this vessel. Additional studies using flow
      spoiled fresh blood imaging (flow-spoiled FBI) and time spatial labeling
      inversion pulse (time-SLIP) methods were effective in determining that the vessel
      was the left jugular vein, and that the continuous venous reflux was a result of
      a venous steal by the right jugular vein. We show that by combining different MRA
      techniques we can effectively achieve diagnosis without resorting to more
      invasive examinations.

PMID- 20677274
TI  - Single breathhold cardiac CINE imaging with multi-echo three-dimensional hybrid
      radial SSFP acquisition.
AB  - PURPOSE: To achieve single breathhold whole heart cardiac CINE imaging with
      improved spatial resolution and temporal resolution by using a multi-echo three
      dimensional (3D) hybrid radial SSFP acquisition. MATERIALS AND METHODS: Multi
      echo 3D hybrid radial SSFP acquisitions were used to acquire cardiac CINE imaging
      within a single breathhold. An optimized interleaving scheme was developed for
      view ordering throughout the cardiac cycle. RESULTS: Whole heart short axis views
      were acquired with a spatial resolution of 1.3 x 1.3 x 8.0 mm(3) and temporal
      resolution of 45 ms, within a single 17 s breathhold. The technique was validated
      on eight healthy volunteers by measuring the left ventricular volume throughout
      the cardiac cycle and comparing with the conventional 2D multiple breathhold
      technique. The left ventricle functional measurement bias of our proposed 3D
      technique from the conventional 2D technique: end diastolic volume -3.3 mL +/-
      13.7 mL, end systolic volume 1.4 mL +/- 6.1 mL, and ejection fraction -1.7% +/-
      4.3%, with high correlations 0.94, 0.97, and 0.91, accordingly. CONCLUSION: A
      multi-echo 3D hybrid radial SSFP acquisition was developed to allow for a whole
      heart cardiac CINE exam in a single breathhold. Cardiac function measurements in
      volunteers compared favorably with the standard multiple breathhold exams.

PMID- 20677275
TI  - Effect of hyoscine butylbromide (HBB) on the uterine corpus: quantitative
      assessment with T2-weighted (T2W) MRI in healthy volunteers.
AB  - PURPOSE: To investigate effects of hyoscine butylbromide (HBB) on the appearance
      of three zonal anatomy of the uterine corpus on T2-weighted images (T2WI).
      MATERIALS AND METHODS: Sagittal T2WI of the pelvis were acquired before and after
      intramuscular administration of HBB with interval of 10 minutes in 22 healthy
      volunteers. By drawing polygonal regions of interest (ROIs), the uterine corpus
      was delineated into outer myometrium (OM), junctional zone (JZ), and endometrium
      (EM) in 20 subjects. Areas (mm(2)) and relative signal intensity (rSI) of each
      layer were compared between pre-HBB and post-HBB administration images by using
      paired t-tests. Histogram analysis was conducted for the uterine layers and
      changes were visualized. RESULTS: Areas of OM were significantly increased (P =
      0.014) and mean rSI of JZ and OM were significantly increased (P = 0.007 and
      0.001, respectively) after administration of HBB. Histogram showed an increase in
      the number of pixels with higher rSI in the OM, which was considered to be caused
      by an increase in interstitial fluid and vascular dilatation. EM did not show
      significant changes. CONCLUSION: Layer-wise ROI analyses demonstrated changes in
      the area and rSI in T2WI of the uterus after HBB administration. Histogram
      analysis contributed to the investigation of signal changes.

PMID- 20677276
TI  - In vivo sodium imaging of human patellar cartilage with a 3D cones sequence at 3
      T and 7 T.
AB  - PURPOSE: To compare signal-to-noise ratios (SNRs) and T*(2) maps at 3 T and 7 T
      using 3D cones from in vivo sodium images of the human knee. MATERIALS AND
      METHODS: Sodium concentration has been shown to correlate with glycosaminoglycan
      content of cartilage and is a possible biomarker of osteoarthritis. Using a 3D
      cones trajectory, 17 subjects were scanned at 3 T and 12 at 7 T using custom-made
      sodium-only and dual-tuned sodium/proton surface coils, at a standard resolution
      (1.3 x 1.3 x 4.0 mm(3)) and a high resolution (1.0 x 1.0 x 2.0 mm(3)). We
      measured the SNR of the images and the T*(2) of cartilage at both 3 T and 7 T.
      RESULTS: The average normalized SNR values of standard-resolution images were
      27.1 and 11.3 at 7 T and 3 T. At high resolution, these average SNR values were
      16.5 and 7.3. Image quality was sufficient to show spatial variations of sodium
      content. The average T*(2) of cartilage was measured as 13.2 +/- 1.5 msec at 7 T
      and 15.5 +/- 1.3 msec at 3 T. CONCLUSION: We acquired sodium images of patellar
      cartilage at 3 T and 7 T in under 26 minutes using 3D cones with high resolution
      and acceptable SNR. The SNR improvement at 7 T over 3 T was within the expected
      range based on the increase in field strength. The measured T*(2) values were
      also consistent with previously published values.

PMID- 20677277
TI  - Efficient flow suppressed MRI improves interscan reproducibility of carotid
      atherosclerosis plaque burden measurements.
AB  - PURPOSE: To determine if better flow suppression can meaningfully improve the
      reproducibility of measurements associated with carotid atherosclerotic disease,
      particularly for lumen and wall areas. MATERIALS AND METHODS: Eighteen subjects
      with carotid artery stenosis identified by duplex ultrasound (11 with 16%-49%
      stenosis; 7 with 50%-79% stenosis) underwent two carotid magnetic resonance
      imaging (MRI) examinations on a 3T scanner with a 4-channel phased array coil.
      High-resolution intermediate-weighted TSE (TR/TE = 4000/8.5 msec, 0.55 mm in
      plane resolution, 2 mm slice thickness, 16 slices, 3-minute scan time) with two
      different flow-suppression techniques (multislice double inversion recovery
      [mDIR] and motion-sensitized driven-equilibrium [MSDE]) were obtained separately.
      For each subject, bilateral arteries were reviewed. One radiologist blinded to
      timepoints, flow suppression techniques, and clinical information measured the
      arterial lumen area, wall area, and total vessel wall area. RESULTS: Compared to
      mDIR, the MSDE technique had a smaller interscan standard deviation (SD) in lumen
      (SD: 3.6 vs. 5.2 mm(2), P = 0.02), wall area measurements (SD: 4.5 vs. 6.4 mm(2),
      P = 0.02), and a trend towards smaller SD in total vessel area measurement (SD:
      4.4 vs. 4.9 mm(2), P = 0.07). CONCLUSION: The results from this study demonstrate
      that vessel wall imaging could quantify atherosclerotic plaque measurements more
      reliably with an improved blood suppression technique. This relationship between
      flow-suppression efficiency and reproducibility of plaque measurements is
      important, as more reliable area measurements will be useful in clinical
      diagnosis and in serial MRI studies that monitor carotid atherosclerotic lesion
      progression and regression.

PMID- 20677278
TI  - Comparison of the high relaxivity Gd chelates P1152 and Gd-BOPTA for contrast
      enhanced MR angiography in rabbits at 1.5 Tesla and 3.0 Tesla.
AB  - PURPOSE: To compare signal-enhancing properties of the high relaxivity Gd
      chelates P1152 and Gd-BOPTA for contrast-enhanced MR angiography (CE-MRA) in
      rabbits at 1.5 Tesla (T) and 3.0T. MATERIALS AND METHODS: Three-dimensional CE
      MRA of the abdominal vasculature was performed in six rabbits using both contrast
      agents at a dose of 0.1 mmol/kg. Data acquisition was carried out during first
      pass and up to 10 min after contrast material administration. CNR was determined
      in aorta, vena cava, and renal cortex. Image quality (5-point scale, 5 = best) of
      first pass MR angiograms was rated by two radiologists. RESULTS: During first
      pass CNR of the aorta was 55.1 +/- 5.8 (P1152) and 40.3 +/- 3.9 (Gd-BOPTA) at
      1.5T (P < 0.05), and 114.9 +/- 9.9 (P1152) and 73.5 +/- 8.1 (Gd-BOPTA) at 3.0T (P
      < 0.05). Both contrast agents showed a comparable decline of CNR within 10 min.
      Image quality was rated 4.8 +/- 0.40 (P1152) and 4.5 +/- 0.50 (Gd-BOPTA) at 1.5T
      (P = 0.17), and 4.8 +/- 0.37 (P1152) and 4.7 +/- 0.47 (Gd-BOPTA) at 3.0T (P =
      0.61). CONCLUSION: The high relaxivity Gd-chelate P1152 offers potential to
      improve image contrast for CE-MRA compared with a clinically approved high
      relaxivity contrast agent.

PMID- 20677279
TI  - MR-based visualization and quantification of three-dimensional flow
      characteristics in the portal venous system.
AB  - PURPOSE: To evaluate the feasibility of time-resolved flow-sensitive MRI for the
      three-dimensional (3D) visualization and quantification of normal and
      pathological portal venous (PV) hemodynamics. MATERIALS AND METHODS: Portal
      venous hemodynamics were evaluated in 18 healthy volunteers and 5 patients with
      liver cirrhosis. ECG- and adaptive respiratory navigator gated flow-sensitive 4D
      MRI (time-resolved 3D MRI with three-directional velocity encoding) was performed
      on a 3 Tesla MR system (TRIO, Siemens, Germany). Qualitative flow analysis was
      achieved using 3D streamlines and time-resolved particle traces originating from
      seven emitter planes precisely placed at anatomical landmarks in the PV system.
      Quantitative analysis included retrospective extraction of regional peak and mean
      velocities and vessel area. Results were compared with standard 2D flow-sensitive
      MRI and to the reference standard Doppler ultrasound. RESULTS: Qualitative flow
      analysis was successfully used in the entire PV system. Venous hemodynamics in
      all major branches in 17 of 18 volunteers and 3 of 5 patients were reliably
      depicted with good interobserver agreement (kappa = 0.62). Quantitative analysis
      revealed no significant differences and moderate agreement for peak velocities
      between 3D MR and 2D MRI (r = 0.46) and Doppler ultrasound (US) (r = 0.35) and
      for mean velocities between 3D and 2D MRI (r = 0.41). The PV area was
      significantly (P < 0.01) higher in 3D and 2D MRI compared with US. CONCLUSION: We
      successfully applied 3D MR velocity mapping in the PV system, providing a
      detailed qualitative and quantitative analysis of normal and pathological
      hemodynamics.

PMID- 20677280
TI  - Improved homogeneity of the transmit field by simultaneous transmission with
      phased array and volume coil.
AB  - PURPOSE: To improve the homogeneity of transmit volume coils at high magnetic
      fields (> or =4 T). Due to radiofrequency (RF) field/tissue interactions at high
      fields, 4 T to 8 T, the transmit profile from head-sized volume coils shows a
      distinctive pattern with relatively strong RF magnetic field B(1) in the center
      of the brain. MATERIALS AND METHODS: In contrast to conventional volume coils at
      high field strengths, surface coil phased arrays can provide increased RF field
      strength peripherally. In theory, simultaneous transmission from these two
      devices could produce a more homogeneous transmission field. To minimize
      interactions between the phased array and the volume coil, counter rotating
      current (CRC) surface coils consisting of two parallel rings carrying opposite
      currents were used for the phased array. RESULTS: Numerical simulations and
      experimental data demonstrate that substantial improvements in transmit field
      homogeneity can be obtained. CONCLUSION: We have demonstrated the feasibility of
      using simultaneous transmission with human head-sized volume coils and CRC phased
      arrays to improve homogeneity of the transmit RF B(1) field for high-field MRI
      systems.

PMID- 20677281
TI  - Ground truth hardware phantoms for validation of diffusion-weighted MRI
      applications.
AB  - PURPOSE: To quantitatively validate diffusion-weighted MRI (DW-MRI) applications,
      a hardware phantom containing crossing fibers at a sub-voxel level is presented.
      It is suitable for validation of a large spectrum of DW-MRI applications from
      acquisition to fiber tracking, which is an important recurrent issue in the
      field. MATERIALS AND METHODS: Phantom properties were optimized to resemble
      properties of human white matter in terms of anisotropy, fractional anisotropy,
      and T(2). Sub-voxel crossings were constructed at angles of 30, 50, and 65
      degrees, by wrapping polyester fibers, with a diameter close to axon diameter,
      into heat shrink tubes. We show our phantoms are suitable for the acquisition of
      DW-MRI data using a clinical protocol. RESULTS: The phantoms can be used to
      successfully estimate both the diffusion tensor and non-Gaussian diffusion
      models, and perform streamline fiber tracking. DOT (Diffusion Orientation
      Transform) and q-ball reconstruction of the diffusion profiles acquired at b =
      3000 s/mm(2) and 132 diffusion directions reveal multimodal diffusion profiles in
      voxels containing crossing yarn strands. CONCLUSION: The highly purpose adaptable
      phantoms provide a DW-MRI validation platform: applications include optimisation
      of acquisition schemes, validation of non-Gaussian diffusion models, comparison
      and validation of fiber tracking algorithms, and quality control in multi-center
      DWI studies.

PMID- 20677282
TI  - Effects of gradient non-linearity correction and intensity non-uniformity
      correction in longitudinal studies using structural image evaluation using
      normalization of atrophy (SIENA).
AB  - PURPOSE: To evaluate the effects of gradient nonlinearity correction and
      intensity nonuniformity correction on longitudinal (two-year) changes in global
      and regional brain volumes. MATERIALS AND METHODS: A total of 208 subjects (70
      females and 138 males, age range = 38.1-83.0 years) were included in this study.
      Each subject was scanned twice, at an interval of approximately two years (range
      = 1.5-2.3 years). Three-dimensional fast spoiled-gradient recalled acquisition in
      the steady state (3D-FSPGR) images corrected for gradient nonlinearity and/or
      intensity nonuniformity were compared with uncorrected 3D-FSPGR images with use
      of structural image evaluation using normalization of atrophy 2.6 (SIENA).
      RESULTS: The mean absolute deviations of percentage brain volume change (PBVC)
      values in the gradient nonlinearity +/- intensity nonuniformity corrected images
      were significantly less than that in the uncorrected images, and the difference
      in the mean absolute deviation of PBVC was the most significant between the
      uncorrected images and the images corrected for both gradient nonlinearity and
      intensity nonuniformity. Voxel-wise comparisons showed large significant
      differences between the uncorrected images and the corrected images. CONCLUSION:
      Correction for gradient nonlinearity and intensity nonuniformity reduces the
      variance of measured longitudinal changes in brain volumes and will improve
      accuracy for detecting subtle brain changes.

PMID- 20677283
TI  - Noise analysis for 3-point chemical shift-based water-fat separation with
      spectral modeling of fat.
AB  - PURPOSE: To model the theoretical signal-to-noise ratio (SNR) behavior of 3-point
      chemical shift-based water-fat separation, using spectral modeling of fat, with
      experimental validation for spin-echo and gradient-echo imaging. The echo
      combination that achieves the best SNR performance for a given spectral model of
      fat was also investigated. MATERIALS AND METHODS: Cramer-Rao bound analysis was
      used to calculate the best possible SNR performance for a given echo combination.
      Experimental validation in a fat-water phantom was performed and compared with
      theory. In vivo scans were performed to compare fat separation with and with out
      spectral modeling of fat. RESULTS: Theoretical SNR calculations for methods that
      include spectral modeling of fat agree closely with experimental SNR
      measurements. Spectral modeling of fat more accurately separates fat and water
      signals, with only a slight decrease in the SNR performance of the water-only
      image, although with a relatively large decrease in the fat SNR performance.
      CONCLUSION: The optimal echo combination that provides the best SNR performance
      for water using spectral modeling of fat is very similar to previous
      optimizations that modeled fat as a single peak. Therefore, the optimal echo
      spacing commonly used for single fat peak models is adequate for most
      applications that use spectral modeling of fat.

PMID- 20677284
TI  - Liver transplantation for non-hepatocellular carcinoma malignancy: Indications,
      limitations, and analysis of the current literature.
AB  - Orthotopic liver transplantation (OLT) is currently incorporated into the
      treatment regimens for specific nonhepatocellular malignancies. For patients
      suffering from early-stage, unresectable hilar cholangiocarcinoma (CCA), OLT
      preceded by neoadjuvant radiotherapy has the potential to readily achieve a tumor
      free margin, accomplish a radical resection, and treat underlying primary
      sclerosing cholangitis when present. In highly selected stage I and II patients
      with CCA, the 5-year survival rate is 80%. As additional data are accrued, OLT
      with neoadjuvant chemoradiation may become a viable alternative to resection for
      patients with localized, node-negative hilar CCA. Hepatic involvement from
      neuroendocrine tumors can be treated with OLT when metastases are unresectable or
      for palliation of medically uncontrollable symptoms. Five-year survival rates as
      high as 90% have been reported, and the Ki67 labeling index can be used to
      predict outcomes after OLT. Hepatic epithelioid hemangioendothelioma is a rare
      tumor of vascular origin. The data from single-institution series are limited,
      but compiled reviews have reported 1- and 10-year survival rates of 96% and 72%,
      respectively. Hepatoblastoma is the most common primary hepatic malignancy in
      children. There exist subtle differences in the timing of chemotherapy between US
      and European centers; however, the long-term survival rate after transplantation
      ranges from 66% to 77%. Fibrolamellar hepatocellular carcinoma is a distinct
      liver malignancy best treated by surgical resection. However, there is an
      increasing amount of data supporting OLT when resection is contraindicated. In
      the treatment of either primary or metastatic hepatic sarcomas, unacceptable
      survival and recurrence rates currently prohibit the use of OLT.

PMID- 20677285
TI  - Validation of a current definition of early allograft dysfunction in liver
      transplant recipients and analysis of risk factors.
AB  - Translational studies in liver transplantation often require an endpoint of graft
      function or dysfunction beyond graft loss. Prior definitions of early allograft
      dysfunction (EAD) vary, and none have been validated in a large multicenter
      population in the Model for End-Stage Liver Disease (MELD) era. We examined an
      updated definition of EAD to validate previously used criteria, and correlated
      this definition with graft and patient outcome. We performed a cohort study of
      300 deceased donor liver transplants at 3 U.S. programs. EAD was defined as the
      presence of one or more of the following previously defined postoperative
      laboratory analyses reflective of liver injury and function: bilirubin
      >or=10mg/dL on day 7, international normalized ratio >or=1.6 on day 7, and
      alanine or aspartate aminotransferases >2000 IU/L within the first 7 days. To
      assess predictive validity, the EAD definition was tested for association with
      graft and patient survival. Risk factors for EAD were assessed using
      multivariable logistic regression. Overall incidence of EAD was 23.2%. Most
      grafts met the definition with increased bilirubin at day 7 or high levels of
      aminotransferases. Of recipients meeting the EAD definition, 18.8% died, as
      opposed to 1.8% of recipients without EAD (relative risk = 10.7 [95% confidence
      interval: 3.6, 31.9] P < 0.0001). More recipients with EAD lost their grafts
      (26.1%) than recipients with no EAD (3.5%) (relative risk = 7.4 [95% confidence
      interval: 3.4, 16.3] P < 0.0001). Donor age and MELD score were significant EAD
      risk factors in a multivariate model. In summary a simple definition of EAD using
      objective posttransplant criteria identified a 23% incidence, and was highly
      associated with graft loss and patient mortality, validating previously published
      criteria. This definition can be used as an endpoint in translational studies
      aiming to identify mechanistic pathways leading to a subgroup of liver grafts
      with clinical expression of suboptimal function.

PMID- 20677286
TI  - Rifaximin for the treatment of recurrent Clostridium difficile infection after
      liver transplantation: A case series.
AB  - Previous data have suggested that the nonsystemic antibiotic rifaximin may be
      effective for the treatment of Clostridium difficile infection (CDI). This single
      center retrospective study evaluated the efficacy of rifaximin for the treatment
      of CDI refractory to standard treatments in patients who had received liver
      transplants. Among 205 patients who had received liver transplants between July
      2001 and December 2007, 3 patients with a confirmed diagnosis of C. difficile
      experienced recurrent diarrhea even though they received standard therapy.
      Patient 1, a 56-year-old male, patient 2, a 62-year-old male, and patient 3, a 73
      year-old female, developed CDIs 190, 318, and 2310 days after transplantation,
      respectively. All patients experienced symptom recurrences after oral
      metronidazole therapy (250 mg 3 times daily for either 14 or 28 days) and after
      oral vancomycin therapy (125 mg 4 times daily for 14 days). Long-term vancomycin
      treatment (ie, 28 days) was required for patients 1 and 2. Vancomycin was
      discontinued in patient 3 because of increased creatinine levels. Oral rifaximin
      (400 mg 3 times daily) was initiated immediately after discontinuation of
      vancomycin therapy. Within 36 to 48 hours of the initiation of rifaximin
      treatment, diarrheal symptoms were resolved in all patients. After completing a
      28-day course of rifaximin, patient 1 remained symptom-free during 185 days of
      follow-up, and patient 2 remained symptom-free during 250 days of follow-up.
      Patient 3 reported no symptoms within 155 days after the completion of rifaximin
      treatment. These findings suggest that rifaximin may be effective for the
      treatment of recurrent CDI and may provide a therapeutic option for CDI in
      immunocompromised patients.

PMID- 20677287
TI  - Six score systems to evaluate candidates with advanced cirrhosis for orthotopic
      liver transplant: Which is the winner?
AB  - Many prognostic systems have been devised to predict the outcome of liver
      transplantation (LT) candidates. Today, the Model for End-Stage Liver Disease
      (MELD) is widely used for organ allocation, but it has shown some limitations.
      The aim of this study was to investigate the performance of MELD compared to 5
      different score models. We evaluated the prognostic ability of MELD, modified
      Child-Turcotte-Pugh, MELD-sodium, United Kingdom MELD, updated MELD, and
      integrated MELD in 487 candidates with cirrhosis for LT at the Bologna Transplant
      Centre, Bologna, Italy, between 2003 and 2008. Calibration analysis by Hosmer
      Lemeshow test, calibration curves, and concordance c-statistics (area under the
      receiver operating characteristic curve [AUC]) were calculated at 3, 6, and 12
      months. Actual cumulative survival curves, taking into account the event of
      interest in the presence of competing risk, were obtained using the best cutoffs
      identified by AUC. For each score, the Hosmer-Lemeshow test revealed a good
      calibration. Integrated MELD showed calibration curves closer to the line of
      perfect predicting ability, followed by MELD-sodium at 3 months and modified
      Child-Turcotte-Pugh at 6 months. MELD-sodium AUCs at 3 and 6 months (0.798 and
      0.765, respectively) and integrated MELD AUC at 6 months (0.792) were better than
      standard MELD (P < 0.05). Actual survival curves showed that these 2 scores were
      able to identify the patients with the highest drop-out risk. In conclusion, MELD
      sodium and integrated MELD were the best prognostic models to predict drop-out
      rates among patients awaiting LT.

PMID- 20677288
TI  - Factors affecting hepatocyte isolation, engraftment, and replication in an in
      vivo model.
AB  - Human hepatocyte transplantation is an alternative treatment for acute liver
      failure and liver diseases involving enzyme deficiencies. Although it has been
      successfully applied in selected recipients, both isolation and transplantation
      outcomes have the potential to be improved by better donor selection. This study
      assessed the impact of various donor variables on isolation outcomes (yield and
      viability) and posttransplant engraftment, using the SCID/Alb-uPA (severe
      combined immunodeficient/urokinase type plasminogen activator under the control
      of an albumin promoter) human liver chimeric mouse model. Human hepatocytes were
      obtained from 90 human liver donor specimens and were transplanted into 3942
      mice. Multivariate analysis revealed improved viability with younger donors (P =
      0.038) as well as with shorter warm ischemic time (P = 0.012). Hepatocyte
      engraftment, assessed by the posttransplant level of serum human alpha1
      antitrypsin, was improved with shorter warm ischemia time. Hepatocytes isolated
      from older donors (>or=60 years) had lower viability and posttransplant
      engraftment (P <or= 0.01). In conclusion, the selection of young donors (<60
      years) and rapid liver specimen retrieval, allowing for shorter warm ischemia
      time, are key determinants for the success of both the isolation of high
      viability human hepatocytes and their subsequent posttransplantation capacity for
      engraftment and expansion.

PMID- 20677289
TI  - Successful outcomes following living donor liver transplantation for
      portopulmonary hypertension.
AB  - Pulmonary arterial hypertension (PAH) associated with portal hypertension
      [portopulmonary hypertension (PPHTN)] occurs in 2% to 10% of patients with
      advanced liver disease and carries a very poor prognosis without treatment. Most
      hepatic transplantation centers consider moderate to severe PPHTN to be a
      contraindication to liver transplantation because of the high rate of
      perioperative complications. We present 3 patients with PPHTN who were managed
      with intravenous prostacyclin therapy followed by living donor liver
      transplantation (LDLT). These individuals demonstrated subsequent resolution of
      their pulmonary hypertension and were weaned off all PAH-specific medical
      therapy. We present their demographics, clinical courses, and hemodynamics. We
      discuss the potential indications for LDLT and risks with respect to this patient
      population. Limitations of the Model for End-Stage Liver Disease scoring system
      and outcome data for this patient population are reviewed. Future studies should
      be directed toward better defining indications for LDLT in patients with PPHTN,
      improving medicosurgical management, and assessing long-term outcomes.

PMID- 20677290
TI  - Pretransplant serum troponin levels are highly predictive of patient and graft
      survival following liver transplantation.
AB  - Optimizing the utility of liver transplantation requires the identification of
      factors that confer increased risk of posttransplant mortality. Elevated serum
      troponin (TN) levels are strongly predictive of posttransplant mortality after
      kidney transplantation. We sought to determine whether pretransplant TN levels
      were predictive of mortality and graft loss after liver transplantation in 236
      liver transplant recipients from 1998 to 2001 with 8.2 years of follow-up.
      Elevated TN levels [hazard ratio (HR) = 2.19, P = 0.004] and a pretransplant
      history of cardiovascular disease (CVD; HR = 1.90, P = 0.031) were predictive of
      patient mortality. Elevated TN levels (HR = 2.44, P < 0.001), a history of CVD
      (HR = 1.83, P = 0.031), and a combination of elevated TN levels and CVD (HR =
      2.75, P = 0.027) were associated with increased graft loss. Multivariate analysis
      confirmed TN and CVD as independent predictors of mortality and graft loss. CVD
      (HR = 2.39, P = 0.032) and a combination of elevated TN levels and a history of
      CVD (HR = 6.67, P < 0.001) were predictive of graft loss within 1 year. Age,
      smoking, diabetes, hypertension, obesity, creatinine levels, and Model for End
      Stage Liver Disease scores were not predictive of posttransplant mortality or
      graft loss. In summary, elevated pretransplant serum TN levels are strongly
      predictive of mortality and graft loss after liver transplantation and may be
      helpful in risk stratification of potential liver transplant recipients.

PMID- 20677291
TI  - Portal vein thrombosis and liver transplant survival benefit.
AB  - Portal vein thrombosis (PVT) complicates the liver transplant operation and
      potentially affects waiting list survival. The implications on calculations of
      survival benefit, which balance both waiting list and posttransplant survival
      effects of PVT, have not been determined. The objective of this study is to
      describe the effect of PVT on the survival benefit of liver transplantation.
      Using Scientific Registry of Transplant Recipients data on adult liver transplant
      candidates wait-listed between September 2001 and December 2007, Cox proportional
      hazard models were fitted to estimate the covariate-adjusted effect of PVT on
      transplant rate, waiting list survival, and posttransplant survival. We then used
      sequential stratification to estimate liver transplant survival benefit by cross
      classifications defined by Model for End-Stage Liver Disease (MELD) score and PVT
      status. The prevalence of reported PVT among 22,291 liver transplant recipients
      was 4.02% (N = 897). PVT was not a predictor of waiting list mortality (hazard
      ratio = 0.90, P = 0.23) but was a predictor of posttransplant mortality (hazard
      ratio = 1.32, P = 0.02). Overall, transplant benefit was not significantly
      different for patients with PVT versus without PVT (P = 0.21), but there was a
      shift in the benefit curve. Specifically, the threshold for transplant benefit
      among patients without PVT was MELD score >11 compared to MELD score >13 for
      patients with PVT. PVT is associated with significantly higher posttransplant
      mortality but does not affect waiting list mortality. Among patients with low
      MELD score, PVT is associated with less transplant survival benefit. Clinicians
      should carefully consider the risks of liver transplantation in clinically stable
      patients who have PVT.

PMID- 20677292
TI  - Microfluidics in inorganic chemistry.
AB  - The application of microfluidics in chemistry has gained significant importance
      in the recent years. Miniaturized chemistry platforms provide controlled fluid
      transport, rapid chemical reactions, and cost-saving advantages over conventional
      reactors. The advantages of microfluidics have been clearly established in the
      field of analytical and bioanalytical sciences and in the field of organic
      synthesis. It is less true in the field of inorganic chemistry and materials
      science; however in inorganic chemistry it has mostly been used for the
      separation and selective extraction of metal ions. Microfluidics has been used in
      materials science mainly for the improvement of nanoparticle synthesis, namely
      metal, metal oxide, and semiconductor nanoparticles. Microfluidic devices can
      also be used for the formulation of more advanced and sophisticated inorganic
      materials or hybrids.

PMID- 20677293
TI  - From nanostructured liquid crystals to polymer-based electrolytes.

PMID- 20677294
TI  - [(MesCu)(2)(eta(3)-Si(4))](4-): a mesitylcopper-stabilized tetrasilicide
      tetraanion.

PMID- 20677295
TI  - An efficient and general synthesis of primary amines by ruthenium-catalyzed
      amination of secondary alcohols with ammonia.

PMID- 20677296
TI  - An efficient oxidation of primary azides catalyzed by copper iodide: a convenient
      method for the synthesis of nitriles.

PMID- 20677298
TI  - Microfluidic gas-flow imaging utilizing parahydrogen-induced polarization and
      remote-detection NMR.

PMID- 20677297
TI  - Poly(ethylene glycol) with observable shedding.

PMID- 20677299
TI  - Treasures from the sea: discovery and total synthesis of ammosamides.

PMID- 20677300
TI  - Consecutive donor-base exchange in anthracenyllithium compounds.

PMID- 20677301
TI  - Selective pulsed heating for the synthesis of semiconductor and metal
      submicrometer spheres.

PMID- 20677302
TI  - Silicon analogues of carboxylic acids: synthesis of isolable silanoic acids by
      donor-acceptor stabilization.

PMID- 20677303
TI  - In situ generation of wavelength-shifting donor-acceptor mixed-monolayer-modified
      surfaces.

PMID- 20677304
TI  - A versatile palladium/triphosphane system for direct arylation of heteroarenes
      with chloroarenes at low catalyst loading.

PMID- 20677305
TI  - Ionic liquids as versatile precursors for functionalized porous carbon and carbon
      oxide composite materials by confined carbonization.

PMID- 20677306
TI  - Efficient synthesis of panchromatic dyes for energy concentration.

PMID- 20677307
TI  - Microarray-assisted high-throughput identification of a cell-permeable small
      molecule binder of 14-3-3 proteins.

PMID- 20677308
TI  - Fluoro-organocatalysts: conformer equivalents as a tool for mechanistic studies.

PMID- 20677309
TI  - A potent trans-diimine platinum anticancer complex photoactivated by visible
      light.

PMID- 20677312
TI  - Photoinduced electron transfer in photorobust coumarins linked with electron
      donors affording long lifetimes of triplet charge-separated states.
AB  - Electron donor (D) substituted 3-ethoxycarbonylcoumarin (CM) derivatives [D-CM: D
      = 4-diphenylaminophenyl (DPA), 4-diethylaminophenyl (DEA), 4-dimethylaminophenyl
      (DMA), and 2-methyl-4-dimethylaminophenyl (MeDMA)] are synthesized and
      characterized. Photoinduced electron transfer (ET) from the D moiety to the
      acceptor (CM) and back electron transfer (BET) are investigated by femtosecond
      and nanosecond laser flash photolysis measurements. Femtosecond laser excitation
      at 355 nm of a deaerated acetonitrile (MeCN) solution of D-CM shows generation of
      the singlet charge-separated (CS) state [(1)(D(.+)-CM(.-))] by ET from D to the
      singlet excited state of the CM moiety ((1)CM*), and this is followed by rapid
      decay within 3 ns to afford the triplet excited state (D-(3)CM*). Nanosecond
      laser excitation of a deaerated MeCN solution of D-CM results in formation of the
      triplet CS state by ET from D to (3)CM*. The quantum yield of formation of the
      triplet CS state [(3)(DPA(.+)-CM(.-))] in the presence of iodobenzene (PhI) in
      deaerated MeCN increases with increasing concentration of PhI to reach 27 % at
      0.5 M PhI. The triplet CS state decays by bimolecular BET because of the long CS
      lifetime by unimolecular BET. Formation of the long-lived triplet CS state was
      confirmed by electron spin resonance (ESR) measurements. The photorobust nature
      of DPA-CM is demonstrated by multiple laser pulse excitation (>1000 times) at 355
      nm. The photoinduced ET and BET rate constants of a series of D-CM are thoroughly
      analyzed in light of the Marcus theory of electron transfer.

PMID- 20677313
TI  - On the reactivity of sulfosalts in cyanide aqueous media: structural, bonding and
      electronic aspects.
AB  - The reactivity of the ruby silver minerals proustite (3Ag(2)S?As(2)S(3)) and
      pyrargyrite (3Ag(2)S?Sb(2)S(3)) was studied with two types of electrodes: a
      carbon-paste electroactive electrode (CPEE) and a paraffin-impregnated graphite
      electrode (PIGE). Polycrystalline samples of alpha-Ag(2)S (acanthite), As(2)S(3)
      (orpiment), Sb(2)S(3) (stibnite), Ag(3)AsS(3) (proustite), Ag(3)SbS(3)
      (pyrargyrite), and three samples of the proustite-pyrargyrite solid solution
      series were synthesized from pure elements by a solid-state reaction method.
      Phase identification of samples was carried out by XRD and chemical homogeneity
      was checked by SEM-EDS. Besides, sulfosalts were characterized by diffuse
      reflectance spectroscopy (DRS). Flat-band and formal potentials of sulfosalts
      were determined by the Mott-Schottky method and differential pulse abrasive
      stripping voltammetry, respectively. Band structure, bonding and solid-state
      structure are considered to investigate the oxidation and reduction of the
      solids. A ligand-to-metal charge transfer (LMCT) transition from the AsS(3) (or
      SbS(3)) group to Ag is related to ease of reducing the pyrargyrite-proustite
      series. Despite the increase in the amount of As (Sb) in Ag(3)SbS(3)
      (Ag(3)AsS(3)), reactivity is similar due to the similarity of the solid-state
      structures, and the same oxidation states of S, As, Sb and Ag species in the
      lattice. However, the nature of the pnictogen (As or Sb) changes the position of
      the conduction and valence band edges and modulates the reactivity of the
      pyrargyrite-proustite series. Anodic dissolution occurs by hole transfer from the
      top of the valence band that is formed mainly by the states of the AsS(3) and
      SbS(3) groups. Meanwhile, silver reduction occurs by electron transfer from the
      Ag 5s orbitals located at the bottom of the conduction band. The difficulty in
      dissolving proustite and pyrargyrite in cyanide is related to the presence of
      pyramidal AsS(3) and SbS(3) groups in these sulfosalts.

PMID- 20677314
TI  - Praziquantel and schistosomiasis.

PMID- 20677315
TI  - Controlled orientation of DNA in a binary SAM as a key for the successful
      determination of DNA hybridization by means of electrochemical impedance
      spectroscopy.
AB  - Determination of DNA hybridization at electrode surfaces modified with thiol
      tethered single-stranded DNA (ssDNA) capture probes and co-assembled with short
      chain thiol derivatives using electrochemical impedance spectroscopy requires a
      careful design of the electrode/electrolyte interface as well as an in-depth
      understanding of the processes at the interface during DNA hybridization. The
      influence of the electrode potential, the ssDNA coverage, the ionic strength, the
      nature of the thiol derivative and especially the Debye length are shown to have
      a significant impact on the impedance spectra. A mixed monolayer comprising--in
      addition to the ssDNA capture probe--both mercaptohexanol (MCH) and
      mercaptopropionic acid (MPA) is suggested as an interface design which allows a
      high efficiency of the DNA hybridization concomitantly with a reliable modulation
      of the charge-transfer resistance of the electrode upon hybridization.

PMID- 20677316
TI  - Adsorption on heterogeneous surfaces: site energy distribution functions from
      Fritz-Schluender isotherms.
AB  - Different site energy distribution functions based on the condensation
      approximation method are proposed for the liquid-phase or gas-phase adsorption
      equilibrium data following the Fritz-Schluender isotherm. Energy distribution
      functions for the four limiting cases of the Fritz-Schluender isotherm are also
      discussed. The proposed models are successfully applied to the experimental
      equilibrium data of nitrogen molecules at 77 K on a pitch-based activated carbon
      (PA) and a pitch-based activated carbon containing boron (PBA). An energy
      distribution function based on FS isotherm containing five parameters suggest a
      unimodal distribution of binding sites for carbon PA, the binding site energies
      being distributed as exponential or unimodal, depending on the pressure, in the
      case of carbon PBA. The advantages of the proposed models are discussed.

PMID- 20677317
TI  - Design, synthesis, and biological evaluation of coumarin derivatives tethered to
      an edrophonium-like fragment as highly potent and selective dual binding site
      acetylcholinesterase inhibitors.
AB  - A large series of substituted coumarins linked through an appropriate spacer to 3
      hydroxy-N,N-dimethylanilino or 3-hydroxy-N,N,N-trialkylbenzaminium moieties were
      synthesized and evaluated as acetylcholinesterase (AChE) and
      butyrylcholinesterase (BChE) inhibitors. The highest AChE inhibitory potency in
      the 3-hydroxy-N,N-dimethylanilino series was observed with a 6,7-dimethoxy-3
      substituted coumarin derivative, which, along with an outstanding affinity
      (IC(50)=0.236 nM) exhibits excellent AChE/BChE selectivity (SI>300 000). Most of
      the synthesized 3-hydroxy-N,N,N-trialkylbenzaminium salts display an AChE
      affinity in the sub-nanomolar to picomolar range along with excellent AChE/BChE
      selectivities (SI values up to 138 333). The combined use of docking and
      molecular dynamics simulations permitted us to shed light on the observed
      structure-affinity and structure-selectivity relationships, to detect two
      possible alternative binding modes, and to assess the critical role of pi-pi
      stacking interactions in the AChE peripheral binding site.

PMID- 20677319
TI  - Synthesis and biological activities of azalamellarins.
AB  - The synthesis of azalamellarins, a new series of lactam analogues of biologically
      active lamellarins, was achieved using Cu(I)-mediated and microwave-assisted C
      N(amide) bond formation. Seventeen azalamellarins, including N
      allylazalamellarins and N-propylazalamellarins chi-D, L-N, and J-dehydro J, were
      synthesized and evaluated for their cytotoxicity against the cancer cell lines
      HuCCA-1, A-549, HepG2, and MOLT-3. The results showed that certain azalamellarins
      exhibited good activities in the micromolar IC(50) value range (IC(50)=the drug
      concentration that causes 50 % of cell-growth inhibition after 72 h of continuous
      exposure to the test molecule), comparable to their parent lamellarin analogue.

PMID- 20677318
TI  - The active core in a triazole peptide dual-site antagonist of HIV-1 gp120.
AB  - In an effort to identify broadly active inhibitors of HIV-1 entry into host
      cells, we previously reported a family of dodecamer triazole-peptide conjugates
      with nanomolar affinity for the viral surface protein gp120. This peptide class
      exhibits potent antiviral activity and the capacity to simultaneously inhibit
      interaction of the viral envelope protein with both CD4 and co-receptor. In this
      investigation, we minimized the structural complexity of the lead triazole
      inhibitor HNG-156 (peptide 1) to explore the limits of the pharmacophore that
      enables dual antagonism and to improve opportunities for peptidomimetic design.
      Truncations of both carboxy- and amino-terminal residues from the parent 12
      residue peptide 1 were found to have minimal effects on both affinity and
      antiviral activity. In contrast, the central triazole(Pro)-Trp cluster at
      residues 6 and 7 with ferrocenyl-triazole(Pro) (Ftp) was found to be critical for
      bioactivity. Amino-terminal residues distal to the central triazole(Pro)-Trp
      sequence tolerated decreasing degrees of side chain variation upon approaching
      the central cluster. A peptide fragment containing residues 3-7 (Asn-Asn-Ile-Ftp
      Trp) exhibited substantial direct binding affinity, antiviral potency, dual
      receptor site antagonism, and induction of gp120 structuring, all properties that
      define the functional signature of the parent compound 1. This active core
      contains a stereochemically specific hydrophobic triazole(Pro)-Trp cluster, with
      a short N-terminal peptide extension providing groups for potential main chain
      and side chain hydrogen bonding. The results of this work argue that the
      pharmacophore for dual antagonism is structurally limited, thereby enhancing the
      potential to develop minimized peptidomimetic HIV-1 entry inhibitors that
      simultaneously suppress binding of envelope protein to both of its host cell
      receptors. The results also argue that the target epitope on gp120 is relatively
      small, pointing to a localized allosteric inhibition site in the HIV-1 envelope
      that could be targeted for small-molecule inhibitor discovery.

PMID- 20677320
TI  - Synthesis, spectroscopy, crystal structure determination, and quantum chemical
      calculations of BODIPY dyes with increasing conformational restriction and
      concomitant red-shifted visible absorption and fluorescence spectra.
AB  - Starting from the conformationally unconstrained compound 3,5-di-(2-bromophenoxy)
      4,4-difluoro-8-(4-methylphenyl)-4-bora-3a,4a-diaza-s-indacene (1), two BODIPY
      dyes (2 and 3) with increasingly rigid conformations were synthesized in
      outstanding total yields through palladium catalyzed intramolecular benzofuran
      formation. Restricted bond rotation of the phenoxy fragments leads to dyes 2 and
      3, which absorb and fluoresce more intensely at longer wavelengths relative to
      the unconstrained dye 1. Reduction of the conformational flexibility in 2 and 3
      leads to significantly higher fluorescence quantum yields compared to those of 1.
      X-ray diffraction analysis shows the progressively more extended planarity of the
      chromophore in line with the increasing conformational restriction in the series
      1-->2-->3, which explains the larger red shifts of the absorption and emission
      spectra. These conclusions are confirmed by quantum chemical calculations of the
      lowest electronic excitations in 1-3 and dyes of related chemical structures. The
      effect of the molecular structure on the visible absorption and fluorescence
      emission properties of 1-3 has been examined as a function of solvent by means of
      the new, generalized treatment of the solvent effect (J. Phys. Chem. B 2009, 113,
      5951-5960). Solvent polarizability is the primary factor responsible for the
      small solvent-dependent shifts of the visible absorption and fluorescence
      emission bands of these dyes.

PMID- 20677322
TI  - The effects of microenvironment polarity and dendritic branching of aliphatic
      hydrocarbon dendrons on the self-assembly of 2-ureido-4-pyrimidinones.
AB  - Two series of aliphatic hydrocarbon-based G1-G3 dendritic 2-ureido-4
      pyrimidinones (UPy) (S-Gn)2 and (L-Gn)2, differing from one another by the
      distance between the branching juncture to the urea end, were prepared and
      characterized. These hydrocarbon dendrons were also appended to a p
      aminonitrobenzene solvatochromic chromophore in order to probe their
      microenvironment polarity. While positive solvatochromism was observed which
      indicated the chromophore was solvent accessible, there was no significant
      difference between the microenvironment polarities on going from the G1 to the G3
      dendrons. The self-assembling behavior and tautomeric preference of the dendritic
      UPy derivatives were examined by 1H NMR spectroscopy. The dimerization constants
      (K(dim*)) of the DDAA tautomers were unchanged at 107 M-1 in CDCl3 at both 25 and
      50 degrees C, which were comparable to those of UPy compounds bearing other
      nonpolar substituents. Furthermore, the lower limits on the K'(dim*) of the DADA
      tautomeric forms of the (S-Gn)2 and (L-Gn)2 series were determined to be 106 and
      105 M-1 in CDCl3, respectively. It was found that a closer proximity of the
      dendron branching juncture to the UPy unit could lead to a destabilization effect
      on the dimeric states. Hence, the (L-Gn)2 dimers are more stable than those of (S
      Gn)2 in the DDAA form, but the latter are more stable than the former in the
      tautomeric DADA state. This study showed that both the highly nonpolar
      microenvironment and the proximity of the dendritic branching juncture to the UPy
      motif could alter the strength and profile of the hydrogen bond-mediated self
      assembling process.

PMID- 20677321
TI  - Sugar-decorated dendritic nanocarriers: encapsulation and release of the
      octahedral rhenium cluster complex [Re6S8(OH)6]4-.
AB  - The encapsulation of a nanometer-sized octahedral anionic rhenium cluster complex
      with six terminal hydroxo ligands [Re(6)S(8)(OH)(6)](4-) in maltose-decorated
      poly(propylene amine) dendrimers (POPAM, generation 4 and 5) has been
      investigated. Ultrafiltration experiments showed that maximal loading capacity of
      the dendrimers with the cluster complex is achieved after about ten hours in
      aqueous solution. To study the inclusion phenomena, three different methods have
      been applied: UV/Vis, time-resolved laser-induced fluorescence spectroscopy
      (TRLFS), and laser-induced liquid bead ion desorption mass spectrometry (LILBID
      MS). From the results obtained, it could be concluded that: a) the hydrolytic
      stability of the rhenium cluster complex is significantly enhanced in the
      presence of dendritic hosts; b) the cluster anions are preferentially bound
      inside the dendrimers; c) the number of cluster complexes encapsulated in the
      dendrimers increases with rising dendrimer generation. On average, four to five
      cluster anions can preferentially be captured in the interior of sugar-coated
      dendritic carriers. An asymptotic progression of the release of cluster complexes
      from the loaded dendrimers was observed under physiologically relevant conditions
      (isotonic sodium chloride solution: approximately 93 % within 4 days for loaded
      POPAM-G4-maltose; approximately 86 % within 4 days for loaded POPAM-G5-maltose).
      These encapsulation and release properties of maltose-decorated nanocarriers
      imply the possibility for the development of the next generation of dendritic
      nanocarriers with specific targeting of destined tissue for therapeutic
      treatments.

PMID- 20677323
TI  - Fabrication of gold-directed conducting polymer nanoarrays for high-performance
      gas sensor.
AB  - Gold-directed polypyrrole (PPy) nanoarrays are fabricated by hydrogel-assisted
      nanotransfer edge printing (HnTEP) and electrochemical polymerization. Gold
      nanoarrays are fabricated through the HnTEP method, which involves metal
      deposition, hydrogel etching, and nanotransfer edge printing. By utilizing the
      well-positioned gold nanostructures, PPy nanoarrays with smooth morphology and
      controllable dimensions are fabricated through in situ electrochemical
      polymerization, the results of which are characterized by scanning electron
      microscopy and atomic force microscopy. A gas sensor based on PPy nanoarrays
      results in excellent sensing capabilities towards NH3 detection, especially the
      sensitivity and fast response. This method appears to be general and may aid in
      the future design and implementation of other active materials which can also be
      manipulated by the same procedure and serve as functional components for chemical
      sensing, optoelectronics, biodetection, and other applications.

PMID- 20677324
TI  - Highly enantioselective Friedel-Crafts-type alkylation reactions of indoles with
      chalcone derivatives using a chiral barium catalyst.

PMID- 20677325
TI  - Preparation of heterocyclic amines by an oxidative amination of zinc
      organometallics mediated by Cu(I): a new oxidative cycloamination for the
      preparation of annulated indole derivatives.
AB  - Functionalized heterocyclic zinc reagents are easily aminated by an oxidative
      amination reaction of zinc amidocuprates prepared from various lithium amides.
      For the oxidation step, PhI(OAc)(2) proved to be the best reagent. The required
      heterocyclic zinc organometallics can be prepared either by direct metalation, by
      magnesium insertion in the presence of ZnCl(2), or by transmetalation of a
      suitable magnesium reagent. Furthermore, we report a new ring-closing reaction
      involving an intramolecular oxidative amination reaction. This reaction allows
      the preparation of tetracyclic heterocycles containing furan, thiophene, or
      indole rings.

PMID- 20677326
TI  - Androgen receptor signaling induced by supraphysiological doses of
      dihydrotestosterone in human peripheral blood lymphocytes.
AB  - Anabolic androgenic steroids, a class of steroid hormones related to
      testosterone, are natural ligands of androgen receptor (AR), a member of the
      nuclear receptor superfamily of ligand-activated transcription factors. AR binds
      specific DNA elements, known as androgen-response elements. Testosterone, the
      main male sexual hormone, binds AR directly and indirectly, through conversion
      into dihydrotestosterone (DHT), its more active metabolite. Anabolic androgenic
      steroids are frequently detected in the urine of doped athletes; their
      consumption is also growing among sport amateurs and adolescents. The effects of
      androgens can differ depending on the target cells and/or tissues. To gain
      insight into transcription activation mechanisms of AR, we investigated AR
      protein signaling in human peripheral blood lymphocytes treated with
      supraphysiological doses of DHT. We performed a comparative proteomic analysis
      and we identified about 30 differentially expressed proteins. At least five
      species contained a consensus androgen-response elements sequence in the promoter
      region of related coding genes. The analysis also revealed that high doses of DHT
      activate the drug detoxification process, could stimulate an increase in cell
      motility and exert a prosurvival effect rather than an apoptotic one.

PMID- 20677327
TI  - The gel electrophoresis markup language (GelML) from the Proteomics Standards
      Initiative.
AB  - The Human Proteome Organisation's Proteomics Standards Initiative has developed
      the GelML (gel electrophoresis markup language) data exchange format for
      representing gel electrophoresis experiments performed in proteomics
      investigations. The format closely follows the reporting guidelines for gel
      electrophoresis, which are part of the Minimum Information About a Proteomics
      Experiment (MIAPE) set of modules. GelML supports the capture of metadata (such
      as experimental protocols) and data (such as gel images) resulting from gel
      electrophoresis so that laboratories can be compliant with the MIAPE Gel
      Electrophoresis guidelines, while allowing such data sets to be exchanged or
      downloaded from public repositories. The format is sufficiently flexible to
      capture data from a broad range of experimental processes, and complements other
      PSI formats for MS data and the results of protein and peptide identifications to
      capture entire gel-based proteome workflows. GelML has resulted from the open
      standardisation process of PSI consisting of both public consultation and
      anonymous review of the specifications.

PMID- 20677328
TI  - Toward a more universal approach in health valuation.
AB  - By polling individual responses to hypothetical scenarios, valuation studies
      estimate population preferences toward health on a quality-adjusted life year
      (QALY) scale. The scenarios typically involve trade-offs in time (time trade-off
      (TTO)), risk (standard gamble (SG)), or number of persons affected (person trade
      off (PTO)). This paper revisits the QALY assumptions and provides a coherent
      health econometric approach that unites TTO, SG, and PTO techniques under a
      common estimator. The proposed approach avoids the use of ratio statistics in
      QALY estimation and the common convention of arbitrarily changing trade-off
      responses. As an example, 34% of the TTO responses from the seminal Measurement
      and Valuation of Health study were changed in the original UK analysis, which led
      to substantially lower QALY estimates. As a general rule, if the original
      estimate is less than 0.5 QALYs, add 0.25 QALYs to get the new estimates.

PMID- 20677329
TI  - Feasibility of a self-help treatment for insomnia comorbid with cancer.
AB  - OBJECTIVE: Professionally administered cognitive-behavioral therapy (CBT) is
      efficacious for treating insomnia in breast cancer survivors. However, given the
      limited accessibility to CBT for insomnia in cancer clinics, there is a need to
      develop other delivery formats for this intervention. This feasibility study
      examined patients' satisfaction with a self-help CBT for insomnia comorbid with
      cancer and gathered some preliminary data on its effect on sleep and associated
      features. METHODS: Eleven breast cancer patients reporting insomnia symptoms
      received a 6-week intervention composed of a 60-min video using an animated
      cartoon format and 6 short booklets developed in French. Patients completed a
      semi-structured interview at post-treatment, a battery of self-report scales and
      a daily sleep diary (14 days) at pre- and post-treatment and at a 3-month follow
      up. RESULTS: At post-treatment interview, comments about the treatment material
      were uniformly positive. On a questionnaire, patients also reported to be
      satisfied with the treatment overall, with the video and the booklets' content,
      as well as with their sleep improvement at post-treatment (scores from 2.7 to
      3.1; scale from 0 to 4). From pre- to post-treatment, moderate-to-large effect
      sizes and statistically and clinically significant differences were found on most
      sleep variables, as well as overall quality of life. These therapeutic gains were
      well sustained at a 3-month follow-up. CONCLUSIONS: Patients were satisfied with
      the treatment received. Although it is too early to draw any firm conclusion,
      treatment outcomes suggest a potential for integration into routine cancer care
      as a first-line sleep management intervention. Copyright (c) 2010 John Wiley &
      Sons, Ltd.

PMID- 20677330
TI  - Bereaved females are more likely to suffer from mood problems even if they do not
      meet the criteria for prolonged grief.
AB  - PURPOSE: The goal of this study was to describe the gender difference of grief
      experience and mood distress among caregivers who cared for terminal cancer
      patients residing in a hospice ward. METHODS: This study recruited 432 caregivers
      who cared for terminal cancer patients in the hospice ward. Caregivers received
      telephone interviews 6 months after the patients had died. The Chinese versions
      of the Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), and
      Inventory of Complicated Grief (ICG) developed in 1995 by Prigerson et al. were
      employed to assess the mood distress and grief status. RESULTS: Total scores of
      BDI, BAI, and ICG were significantly higher in females. Six out of twenty-one
      items of BDI, lack of satisfaction, crying spells, sleep disturbance,
      fatigability, somatic preoccupation, and loss of libido, showed significantly
      higher scores in females. According to BAI, inability to relax, dizziness, fear
      of dying, fright, flushed face, and hot/cold sweats were significantly higher in
      females. After adjustment for potential confounders, the results show that female
      gender is associated with higher BDI (regression coefficient 3.24, 95% CI: 1.48
      4.99), BAI (3.8; 1.11-6.50), and ICG (4.25, 1.09-7.40). Dichotomizing the BDI,
      BAI, and ICG into severe and nonsevere cases, the results showed that gender only
      contributes to severe anxiety status (BAI >= 36), but not to severe depression
      (BDI >= 29) or to prolonged grief (ICG >= 25). CONCLUSIONS: Bereaved females had
      higher scores for depression and anxiety than males. Female gender is associated
      with severe anxiety; however, it is not associated with severe depression or
      prolonged grief.

PMID- 20677331
TI  - The evolution of worry after breast cancer risk assessment: 6-year follow-up of
      the TRACE study cohort.
AB  - OBJECTIVES: There is little evidence regarding the long-term psychological
      implications of breast cancer risk assessment for women at moderate genetic risk.
      A follow-up study of a trial cohort was conducted to evaluate psychological
      outcomes and their predictors at 6-year follow-up. A further aim was to examine
      threshold scores for high cancer worry. METHODS: Questionnaires were sent to 384
      women assessed as moderate risk during a UK trial of genetic assessment (TRACE).
      Measures included cancer worry, perceived risk, health behaviours, general
      anxiety, psychological morbidity, optimism, and background variables assessed
      during TRACE and at 6-year follow-up. RESULTS: Reductions from baseline cancer
      worry and breast self-examination (BrSE) frequency were maintained 6 years after
      risk assessment, with relatively consistent levels over short- and long-term
      follow-up. Provision of risk information led to short-term reductions in
      perceived risk. During the 6-year period, 43% of women reported having made
      lifestyle changes and 27% had requested a mammogram. Baseline and post-risk
      cancer worry were the only significant predictors of long-term cancer worry.
      Greater worry at baseline predicted more frequent BrSE and higher perceived risk,
      but not lifestyle change or mammogram requests, at 6 years. Eighteen percent of
      women reported cancer worry above a threshold of 12.5 at long-term follow-up,
      compared with 30% at baseline. CONCLUSIONS: Overall reductions in cancer worry
      following moderate risk assessment were maintained in the long term. However,
      women at risk of sustained high cancer worry should be identified at an early
      stage in the risk assessment process for more intensive psycho-educational
      intervention. Copyright (c) 2010 John Wiley & Sons, Ltd.

PMID- 20677332
TI  - Non-viral causes of hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and
      represents an international public health concern as one of the most deadly
      cancers worldwide. The main etiology of HCC is chronic infection with hepatitis B
      and hepatitis C viruses. However, there are other important factors that
      contribute to the international burden of HCC. Among these are obesity, diabetes,
      non-alcoholic steatohepatitis and dietary exposures. Emerging evidence suggests
      that the etiology of many cases of HCC is in fact multifactorial, encompassing
      infectious etiologies, comorbid conditions and environmental exposures.
      Clarification of relevant non-viral causes of HCC will aid in preventative
      efforts to curb the rising incidence of this disease.

PMID- 20677334
TI  - Colonoscopic polypectomy and associated techniques.
AB  - Polypectomy of colonic polyps has been shown to reduce the risk of colon cancer
      development and is considered a fundamental skill for all endoscopists who
      perform colonoscopy. A variety of polypectomy techniques and devices are
      available, and their use can vary greatly based on local availability and
      preferences. In general, cold forceps and cold snare have been the polypectomy
      methods of choice for smaller polyps, and hot snare has been the method of choice
      for larger polyps. The use of hot forceps has mostly fallen out of favor.
      Polypectomy for difficult to remove polyps may require the use of special devices
      and advanced techniques and has continued to evolve. As a result, the vast
      majority of polyps today can be removed endoscopically. Since electrocautery is
      frequently used for polypectomy, endoscopists should be thoroughly familiar with
      the basic principles of electrosurgery as it pertains to polypectomy. Tattooing
      of a polypectomy site is an important adjunct to polypectomy and can greatly
      facilitate future surgery or endoscopic surveillance. The two most common post
      polypectomy complications are bleeding and perforation. Their incidence can be
      decreased with the use of meticulous polypectomy techniques and the application
      of some prophylactic maneuvers. This review will examine the technique of
      polypectomy and its complications from the perspective of the practicing
      gastroenterologist.

PMID- 20677335
TI  - Interleukin-21 triggers effector cell responses in the gut.
AB  - In the gut of patients with Crohn's disease and patients with ulcerative colitis,
      the major forms of inflammatory bowel diseases (IBD) in humans, the tissue
      damaging immune response is mediated by an active cross-talk between immune and
      non-immune cells. Accumulating evidence indicates also that cytokines produced by
      these cells play a major role in initiating and shaping this pathologic process.
      One such cytokine seems to be interleukin (IL)-21, a member of the common gamma
      chain-receptor family. IL-21 is produced in excess in the inflamed intestine of
      patients with IBD mostly by activated CD4+ T helper cells co-expressing
      interferon-gamma and follicular T helper cells. Moreover, both in vitro and in
      vivo studies indicate that excessive IL-21 production leads to the activation of
      multiple signaling pathways that expand and sustain the ongoing mucosal
      inflammation. In this article, we review the available data supporting the
      pathogenic role of IL-21 in IBD.

PMID- 20677336
TI  - Non-peptidyl low molecular weight radical scavenger IAC attenuates DSS-induced
      colitis in rats.
AB  - AIM: To investigate the effects of the free radical scavenger bis(1-hydroxy
      2,2,6,6-tetramethyl-4-piperidinyl)decandioate (IAC) in the dextran sodium
      sulphate (DSS) experimental model of ulcerative colitis. METHODS: Colitis was
      induced in Sprague Dawley male rats by administration of 5% DSS in drinking
      water. IAC (30 mg/kg, lipophilic or hydrophilic form) was administered daily
      (orally or ip) for 6 d until sacrifice. Colonic damage was assessed by means of
      indirect (Disease Activity Index score) and direct measures (macroscopic and
      microscopic scores) and myeloperoxidase (MPO) activity. Neutrophil infiltration
      within the tissue and glutathione S-transferase activity were also investigated.
      RESULTS: DSS-induced colitis impaired body weight gain and markedly increased all
      inflammatory parameters. Six-day treatment with lipophilic IAC significantly
      reduced intestinal damage caused by inflammation, induced a down-regulation in
      MPO activity (0.72 +/- 0.12 and 0.45 +/- 0.12 with lipophilic IAC po and ip,
      respectively, vs 1.10 +/- 0.27 in untreated DSS colitis animals) and minimized
      DSS-induced neutrophil infiltration, while hydrophilic IAC administered orally
      did not ameliorate DSS-induced damage. CONCLUSION: These results support the
      hypothesis that reactive oxygen metabolites contribute to inflammation and that
      the radical scavenger IAC has therapeutic potential in inflammatory bowel
      disease.

PMID- 20677333
TI  - Primary biliary cirrhosis: what do autoantibodies tell us?
AB  - Primary biliary cirrhosis (PBC) is a chronic, progressive, cholestatic, organ
      specific autoimmune disease of unknown etiology. It predominantly affects middle
      aged women, and is characterized by autoimmune-mediated destruction of small- and
      medium-size intrahepatic bile ducts, portal inflammation and progressive
      scarring, which without proper treatment can ultimately lead to fibrosis and
      hepatic failure. Serum autoantibodies are crucial tools for differential
      diagnosis of PBC. While it is currently accepted that antimitochondrial
      antibodies are the most important serological markers of PBC, during the last
      five decades more than sixty autoantibodies have been explored in these patients,
      some of which had previously been thought to be specific for other autoimmune
      diseases.

PMID- 20677338
TI  - Proteomic analysis reveals molecular biological details in varioliform gastritis
      without Helicobacter pylori infection.
AB  - AIM: To investigate and elucidate the molecular mechanism underlying varioliform
      gastritis for early detection, prevention and intervention of gastric cancer.
      METHODS: A combination of two-dimensional gel electrophoresis and mass
      spectrometry was used to detect the differentially expressed proteins between
      varioliform gastritis and matched normal mucosa. The selected proteins were
      confirmed by Western blotting and reverse transcription polymerase chain reaction
      (RT-PCR) in additional samples and the function of some proteins in varioliform
      gastritis was analyzed by bio-method preliminarily. RESULTS: We identified 21
      differentially expressed proteins in varioliform gastritis, and compared them
      with matched normal mucosa. Eleven proteins were upregulated and ten
      downregulated in varioliform gastritis when compared with the same proteins in
      individual-matched normal gastric mucosa. These proteins are related to
      metabolism, oxidation, cytoskeleton, apoptosis, signal transduction and other
      aspects of cells. Two novel proteins, thioredoxin domain-containing protein 5
      (TXNDC5) upregulated in varioliform gastritis, and neuropolypeptide h3
      [phosphatidylethanolamine-binding protein 1 (PEBP1)] downregulated in varioliform
      gastritis, were further investigated. Their expressions were validated by Western
      blotting and RT-PCR in 12 cases of varioliform gastritis which was matched with
      normal mucosa. The expression level of PEBP1 in varioliform gastritis was
      significantly lower (P < 0.05) while that of TXNDC5 was significantly higher than
      that in matched normal gastric mucosa (P < 0.05). CONCLUSION: There are some
      changes of protein expression in varioliform gastritis. Downregulation of PEBP1
      and upregulation of TXNDC5 are involved in the development of varioliform
      gastritis.

PMID- 20677337
TI  - Effects of protein deprivation and re-feeding on P2X2 receptors in enteric
      neurons.
AB  - AIM: To investigate the effects of malnutrition and re-feeding on the P2X(2)
      receptor, nitric oxide synthase (NOS), calretinin, calbindin and choline
      acetyltransferase (ChAT) in neurons of the rat ileum. METHODS: We analyzed the co
      localization, numbers and sizes of P2X(2)-expressing neurons in relation to NOS
      immunoreactive (IR), calbindin-IR, ChAT-IR, and calretinin-IR neurons of the
      myenteric and submucosal plexus. The experimental groups consisted of: (1) rats
      maintained on normal feed throughout pregnancy until 42 d post-parturition (N);
      (2) rats deprived of protein throughout pregnancy and 42 d post-parturition (D);
      and (3) rats undernourished for 21 d post-parturition and then given a protein
      diet from days 22 to 42 (DR). The myenteric and submucosal plexuses were
      evaluated by double labeling by immunohistochemical methods for P2X(2) receptor,
      NOS, ChAT, calbindin and calretinin. RESULTS: We found similar P2X(2) receptor
      immunoreactivity in the cytoplasm and surface membranes of myenteric and
      submucosal neurons from the N, D and DR groups. Double labeling of the myenteric
      plexus demonstrated that approximately 100% of NOS-IR, calbindin-IR, calretinin
      IR and ChAT-IR neurons in all groups also expressed the P2X(2) receptor. In the
      submucosal plexus, the calretinin-IR, ChAT-IR and calbindin-IR neurons were
      nearly all immunoreactive for the P2X(2) receptor. In the myenteric plexus, there
      was a 19% increase in numbers per cm(2) for P2X(2) receptor-IR neurons, 64% for
      NOS-IR, 84% for calretinin-IR and 26% for ChAT-IR neurons in the D group. The
      spatial density of calbindin-IR neurons, however, did not differ among the three
      groups. The submucosal neuronal density increased for calbindin-IR, calretinin-IR
      and ChAT-IR neurons. The average size of neurons in the myenteric plexus neurons
      in the D group was less than that in the controls and, in the re-fed rats; there
      was a 34% reduction in size only for the calretinin-IR neurons. CONCLUSION: This
      work demonstrates that expression of the P2X(2) receptor is present in
      inhibitory, intrinsic primary afferent, cholinergic secretomotor and vasomotor
      neurons. Undernutrition affected P2X(2) receptor expression in the submucosal
      plexus, and neuronal and size. These changes were rescued in the re-fed rats.

PMID- 20677339
TI  - Magnetically labeled mesenchymal stem cells after autologous transplantation into
      acutely injured liver.
AB  - AIM: To evaluate tracking of magnetically labeled mesenchymal stem cells (MSCs)
      after intraportal transplantation. METHODS: Mononuclear cells were isolated from
      bone marrow aspirates of pigs by density gradient centrifugation, cultured and
      expanded, after which, they were incubated with super paramagnetic iron oxide
      (SPIO). Prussian blue staining was performed to highlight intracellular iron. To
      establish swine models of acute liver injury, 0.5 g/kg D-galactosamine was
      administrated to 10 pigs, six of which were injected via their portal veins with
      SPIO-labeled MSCs, while the remaining four were injected with unlabeled cells.
      Magnetic resonance imaging (MRI) was performed with a clinical 1.5T MR scanner
      immediately before transplantation and 6 h, 3 d, 7 d and 14 d after
      transplantation. Prussian blue staining was again performed with the tissue
      slices at the endpoint. RESULTS: Prussian blue staining of SPIO-labeled MSCs had
      a labeling efficiency of almost 100%. Signal intensity loss in the liver by SPIO
      labeling on the FFE (T2*WI) sequence persisted until 14 d after transplantation.
      Histological analysis by Prussian blue staining confirmed homing of labeled MSCs
      in the liver after 14 d; primarily distributed in hepatic sinusoids and liver
      parenchyma. CONCLUSION: MSCs were successfully labeled with SPIO in vitro. MRI
      can monitor magnetically labeled MSCs transplanted into the liver.

PMID- 20677340
TI  - ICC density predicts bacterial overgrowth in a rat model of post-infectious IBS.
AB  - AIM: To investigate the interstitial cells of Cajal (ICC) number using a new rat
      model. METHODS: Sprague-Dawley rats were assigned to two groups. The first group
      received gavage with Campylobacter jejuni (C. jejuni) 81-176. The second group
      was gavaged with placebo. Three months after clearance of Campylobacter from the
      stool, precise segments of duodenum, jejunum, and ileum were ligated in self
      contained loops of bowel that were preserved in anaerobic bags. Deep muscular
      plexus ICC (DMP-ICC) were quantified by two blinded readers assessing the tissue
      in a random, coded order. The number of ICC per villus was compared among
      controls, Campylobacter recovered rats without small intestinal bacterial
      overgrowth (SIBO), and Campylobacter recovered rats with SIBO. RESULTS: Three
      months after recovery, 27% of rats gavaged with C. jejuni had SIBO. The rats with
      SIBO had a lower number of DMP-ICC than controls in the jejunum and ileum.
      Additionally there appeared to be a density threshold of 0.12 DMP-ICC/villus that
      was associated with SIBO. If ileal density of DMP-ICC was < 0.12 ICC/villus, 54%
      of rats had SIBO compared to 9% among ileal sections with > 0.12 (P < 0.05). If
      the density of ICC was < 0.12 DMP-ICC/villus in more than one location of the
      bowel, 88% of these had SIBO compared to 6% in those who did not (P < 0.001).
      CONCLUSION: In this post-infectious rat model, the development of SIBO appears to
      be associated with a reduction in DMP-ICC. Further study of this rat model might
      help understand the pathophysiology of post-infectious irritable bowel syndrome.

PMID- 20677341
TI  - Is chronic hepatitis C virus infection a risk factor for breast cancer?
AB  - AIM: To evaluate the prevalence of breast tumors in adult females with chronic
      hepatitis C virus (HCV) infection. METHODS: Prospective, single-center study,
      based on female outpatients consulting in a liver unit, for 1 year. The study
      group included females with present and/or past history of chronic infection by
      HCV. Patients with spontaneous recovery were excluded. Chronic hepatitis had been
      proved by liver biopsy in the majority of cases and/or biological markers of
      inflammation and fibrosis. The control group included female patients with other
      well documented chronic liver diseases: chronic hepatitis B, alcoholic liver
      disease, autoimmune hepatitis, hemochromatosis, non alcoholic liver disease,
      chronic cholangitis. Participating patients were prospectively questioned during
      consultation about past breast history and follow-up by mammography. RESULTS:
      Breast carcinoma was recorded in 17/294 patients with HCV infection (5.8%, 95%
      CI: 3.1-8.4) vs 5/107 control patients (4.7%, 95% CI: 0.67-8.67). Benign tumors
      of the breast (mastosis, nodules, cysts) were recorded in 75/294 patients with
      HCV infection (25.5%, 95% CI: 20.5-30.5) vs 21/107 (19.6%, 95% CI: 12.1-27.1) in
      the control group. No lesion was noted in 202 patients with HCV (68.7%, 95% CI:
      63.4-74) vs 81 control patients (75.7%, 95% CI: 67.6-83.8). Despite a trend to an
      increased prevalence in the group with HCV infection, the difference was not
      significant compared to the control group (P = NS). In patients over 40 years,
      the results were, respectively, as follows: breast cancer associated with HCV:
      17/266 patients (6.3%, 95% CI: 3.4-9.3) vs 5/95 patients (5.2%, 95% CI: 0.7-9.7)
      in the control group; benign breast tumors: 72/266 patients with HCV infection
      (27%, 95% CI: 21.7-32.4) vs 18/95 patients (18.9%, 95% CI: 11-26.8) in the
      control group; no breast lesion 177/266 (66.5%, 95% CI: 60.9-72.2) in patients
      with HCV infection vs 72/95 (75.7%, 95% CI: 67.1-84.4) in the control group. The
      differences were not significant (P = NS). CONCLUSION: These results suggest that
      chronic HCV infection is not a strong promoter of breast carcinoma in adult
      females of any age.

PMID- 20677343
TI  - Approach to early-onset colorectal cancer: clinicopathological, familial,
      molecular and immunohistochemical characteristics.
AB  - AIM: To characterize clinicopathological and familial features of early-onset
      colorectal cancer (CRC) and compare features of tumors with and without
      microsatellite instability (MSI). METHODS: Forty-five patients with CRC aged 45
      or younger were included in the study. Clinical information, a three-generation
      family history, and tumor samples were obtained. MSI status was analyzed and
      mismatch repair genes were examined in the MSI families. Tumors were included in
      a tissue microarray and an immunohistochemical study was carried out with a panel
      of selected antibodies. RESULTS: Early onset CRC is characterized by advanced
      stage at diagnosis, right colon location, low-grade of differentiation, mucin
      production, and presence of polyps. Hereditary forms represent at least 21% of
      cases. Eighty-one percent of patients who died during follow-up showed a lack of
      expression of cyclin E, which could be a marker of poor prognosis. beta-catenin
      expression was normal in a high percentage of tumors. CONCLUSION: Early-onset CRC
      has an important familial component, with a high proportion of tumors showing
      microsatellite stable. Cyclin E might be a poor prognosis factor.

PMID- 20677342
TI  - Nasogastric or nasointestinal feeding in severe acute pancreatitis.
AB  - AIM: To assess the rate of spontaneous tube migration and to compare the effects
      of naso-gastric and naso-intestinal (NI) (beyond the ligament of Treitz) feeding
      in severe acute pancreatitis (SAP). METHODS: After bedside intragastric
      insertion, tube position was assessed, and enteral nutrition (EN) started at day
      4, irrespective of tube localization. Patients were monitored daily and clinical
      and laboratory parameters evaluated to compare the outcome of patients with
      nasogastric (NG) or NI tube. RESULTS: Spontaneous tube migration to a NI site
      occurred in 10/25 (40%) prospectively enrolled SAP patients, while in 15 (60%)
      nutrition was started with a NG tube. Groups were similar for demographics and
      pancreatitis aetiology but computed tomography (CT) severity index was higher in
      NG tube patients than in NI (mean 6.2 vs 4.7, P = 0.04). The CT index seemed a
      risk factor for failed obtainment of spontaneous distal migration. EN trough NG
      or NI tube were similar in terms of tolerability, safety, clinical goals,
      complications and hospital stay. CONCLUSION: Spontaneous distal tube migration is
      successful in 40% of SAP patients, with higher CT severity index predicting
      intragastric retention; in such cases EN by NG tubes seems to provide a pragmatic
      alternative opportunity with similar outcomes.

PMID- 20677344
TI  - Is autoimmune hepatitis a frequent finding among HCV patients with intense
      interface hepatitis?
AB  - AIM: To evaluate the overlap of autoimmune hepatitis in hepatitis C virus (HCV)
      infected patients with intense interface hepatitis. METHODS: Among 1759 patients
      with hepatitis C submitted to liver biopsy, 92 (5.2%) presented intense interface
      hepatitis. These patients were evaluated regarding the presence of antinuclear
      antibody (ANA), anti-smooth muscle antibody (SMA) and anti-liver/kidney
      microsomal antibody (LKM-1), levels of gamma-globulin and histological findings
      related to autoimmune hepatitis (plasma cell infiltrate and presence of
      rosettes). RESULTS: Among patients with hepatitis C and intense interface
      hepatitis there was a low prevalence of autoantibodies (ANA = 12%, SMA = 5%, LKM
      1 = 0%) and the median gamma-globulin level was within the normal range. Typical
      histological findings of autoimmune disease were observed in only two cases (2%).
      After applying the score for diagnosis of autoimmune hepatitis, only one patient
      was classified with a definitive diagnosis of autoimmune hepatitis. Since overlap
      with autoimmune hepatitis was not the explanation for the intense
      necroinflammatory activity in patients with chronic hepatitis C we sought to
      identify the variables associated with this finding. The presence of intense
      interface hepatitis was associated with more advanced age, both at the time of
      infection and at the time of the biopsy, and higher prevalence of blood
      transfusion and alcohol abuse. CONCLUSION: Although possible, overlap with
      autoimmune hepatitis is a very rare association in HCV-infected patients with
      intense interface hepatitis, an unusual presentation which seems to be related to
      other host variables.

PMID- 20677345
TI  - Capecitabine with radiation is an effective adjuvant therapy in gastric cancers.
AB  - AIM: To analyze the outcome of patients who received concurrent capecitabine
      (Xeloda) and radiation (XRT) compared to the established concurrent 5
      fluorouracil (5-FU) with radiation (5FU-RT) and fluoropyrimidine-based
      chemotherapy alone as adjuvant treatment in gastric cancers. METHODS: All
      patients with gastric cancers who received adjuvant treatment at the National
      Cancer Centre Singapore between 1996 and 2006 were reviewed. Treatment outcomes
      of patients who received XRT were compared with those who had 5FU-RT or
      chemotherapy alone as adjuvant therapy for gastric cancers. RESULTS: A total of
      108 patients were reviewed. Median age at diagnosis was 60. The majority of the
      patients (64.8%) had advanced stage III and IV disease (with no distant
      metastasis). All except 4 patients had D2 gastrectomy. Twenty one patients
      (19.4%) had positive surgical resection margins. Thirty three patients received
      XRT compared with 52 who had 5FU-RT and 23 who received chemotherapy alone. For
      the patients in the chemotherapy-only group, all had fluoropyrimidine-based
      therapy, with added cisplatin in 7 patients and epirubicin in 2 patients. Median
      recurrence-free survival was longer for the XRT group (52 mo) compared to the 5FU
      RT (35 mo) and chemotherapy-only groups (25 mo) (P = 0.48). The patients in the
      XRT group achieved similar median overall survival (53 mo) as the 5FU-RT (54 mo)
      and the chemotherapy-only groups (44 mo) (P = 0.5). CONCLUSION: Capecitabine with
      concurrent radiation was as effective as concurrent 5FU with radiation or
      fluoropyrimidine-based chemotherapy alone when used as adjuvant treatment in
      patients with gastric cancers.

PMID- 20677346
TI  - Stent-grafts placement for treatment of massive hemorrhage from ruptured hepatic
      artery after pancreaticoduodenectomy.
AB  - AIM: To present a series of cases with life-threatening hemorrhage from ruptured
      hepatic artery pseudoaneurysm after pancreaticoduodenectomy (PD) treated with
      placement of stent-grafts. METHODS: Massive hemorrhage from ruptured hepatic
      artery pseudoaneurysm after PD in 9 patients (6 men, 3 women) at the age of 23-75
      years (mean 48 years), were treated with placement of percutaneous endovascular
      balloon-expandable coronary stent-grafts. All patients were not suitable for
      embolization because of a non-patent portal vein. One or more stent-grafts,
      ranging 3-6 mm in diameter and 16-55 mm in length, were placed to exclude
      ruptured pseudoaneurysm. Follow-up data, including clinical condition, liver
      function tests, and Doppler ultrasound examination, were recorded at the
      outpatient clinic. RESULTS: Immediate technical success was achieved in all the 9
      patients. All stent-grafts were deployed in the intended position for immediate
      cessation of bleeding and preservation of satisfactory hepatic arterial blood
      flow. No significant procedure-related complications occurred. Recurrent bleeding
      occurred in 2 patients at 16 and 24 h, respectively, after placement of stent
      grafts and treated with surgical revision. One patient died of sepsis 12 d after
      the interventional procedure. The remaining 6 patients were survived when they
      were discharged. The mean follow-up time was 10.5 mo (range 4-16 mo). No patient
      had recurrent bleeding after discharge. Doppler ultrasound examination verified
      the patency of hepatic artery and stent-grafts during the follow-up. CONCLUSION:
      Placement of stent-grafts is an effective and safe procedure for acute life
      threatening hemorrhage from ruptured hepatic artery pseudoaneurysm.

PMID- 20677347
TI  - Right anterior segmental hepatic duct emptying directly into the cystic duct in a
      living donor.
AB  - A 35-year-old mother was scheduled to be the living donor for liver
      transplantation to her second son, who suffered from biliary atresia complicated
      with biliary cirrhosis at the age of 2 years. The operative plan was to recover
      the left lateral segment of the mother's liver for living donor transplantation.
      With the use of cholangiography at the time of surgery, we found the right
      anterior segmental duct (RASD) emptying directly into the cystic duct, and the
      catheter passed into the RASD. After repairing the incision in the cystic duct,
      transplantation was successfully performed. Her postoperative course was
      uneventful. Biliary anatomical variations were frequently encountered, however,
      this variation has very rarely been reported. If the RASD was divided, the repair
      would be very difficult because the duct will not dilate sufficiently in an
      otherwise healthy donor. Meticulous preoperative evaluation of the living donor's
      biliary anatomy, especially using magnetic resonance cholangiography and careful
      intraoperative techniques, is important to prevent bile duct injury and avoid the
      risk to the healthy donor.

PMID- 20677348
TI  - Ultrasonography of sclerosing angiomatoid nodular transformation in the spleen.
AB  - We report three rare cases of sclerosing angiomatoid nodular transformation
      (SANT) in the spleen. We compared the conventional and contrast-enhanced
      ultrasonographic appearance. The conventional sonographic examinations exhibited
      solitary lesions without common respects, while contrast-enhanced ultrasonography
      (CEUS) revealed nodular appearance mimicking its pathologic characteristics. It
      suggests that CEUS can provide morphologic information for diagnosing SANT.

PMID- 20677350
TI  - Cell motility: Swimming skills.

PMID- 20677349
TI  - Leukaemia: MLL makes friends and influences.

PMID- 20677351
TI  - Metastasis: It's nicer with DICER.

PMID- 20677352
TI  - DNA damage: "Curiouser and curiouser!" cried Alice.

PMID- 20677353
TI  - Tumorigenesis: Might as well face it, you're addicted to MYC.

PMID- 20677354
TI  - Angiogenesis: Reducing risk.

PMID- 20677355
TI  - Prostate cancer: A new tARget.

PMID- 20677356
TI  - Small RNAs: Pseudogenes act as microRNA decoys.

PMID- 20677357
TI  - Chromosome instability: RB moonlights in mitosis.

PMID- 20677358
TI  - Regulatory T cells: A helping hand from Bacteroides fragilis.

PMID- 20677360
TI  - B cells: Bad for the heart?

PMID- 20677359
TI  - Tissue morphogenesis coupled with cell shape changes.
AB  - When different tissues successively emerge during development, they need to be
      morphologically segregated from each other. Morphological segregation of tissues
      is often accompanied by robust changes in cell shape, and these two events are
      precisely coordinated. We overview recent progress in understanding how such
      coordination is regulated at the cellular and molecular levels using vertebrate
      somitogenesis asa unique model. In the formation of the somitic gap and its
      concomitant cell epithelialization, Ephrin-Eph intercellular signals play a
      central role, with Ephrin transducing intracellular signals via suppression of
      Cdc42. These signals lead to the activation of integrin where the segment border
      of somites forms, which in turn induces the assembly of fibronectin, the final
      player for the coordination. Intimate coupling of tissue-shape and cell-shape
      changes is also relevant to tumor suppression.

PMID- 20677361
TI  - Glove testing, dermal exposure and hydration as protection against heat stress.

PMID- 20677362
TI  - Lenient versus strict rate control in atrial fibrillation.

PMID- 20677363
TI  - Lenient versus strict rate control in atrial fibrillation.

PMID- 20677364
TI  - Epidural analgesia for labor and delivery.

PMID- 20677365
TI  - Commentary by Fredericks.

PMID- 20677366
TI  - When are glasses medicine?

PMID- 20677367
TI  - Krill phosphatidylserine improves learning and memory in Morris water maze in
      aged rats.
AB  - The ameliorating effect of phosphatidylserine (PS) isolated from krill (KR-PS) on
      the learning and memory deficits associated with normal aging in rats was
      investigated, as compared with soybean PS (SOY-PS). Rats were orally administered
      with KR-PS (20, 50 mg kg-1) and SOY-PS (50 mg kg-1) daily, for 7 days, 30 min
      before behavioral assessment using the Morris water maze (MWM). Changes in the
      cholinergic system were examined by measuring choline acetyltransferase (ChAT)
      and acetylcholinesterase (AchE) immunoreactivity in the hippocampus. The daily
      administration of KR-PS produced a significant improvement in the escape latency
      for finding the platform in the MWM, as compared with SOY-PS. Consistent with the
      behavioral results, KR-PS treatments significantly alleviated age-associated
      losses of cholinergic immunoreactivity, and muscarinic acetylcholine receptor
      type 1 (mAChR-M1) and choline transporter (CHT) mRNA expression in the
      hippocampus. These findings demonstrate that KR-PS showed significant
      neuroprotective activity against the neuronal and cognitive impairments that
      occur with normal aging in rats; comparable results were obtained with SOY-PS.
      These data indicate that oral administration of PS derived from marine life could
      substitute for bovine cerebral cortex PS (BC-PS) as therapy for the improvement
      of diminished memory function in elderly people.

PMID- 20677368
TI  - Vagus-nerve stimulation is tolerated in a patient with cardiac AV-Blocks.

PMID- 20677369
TI  - What is behavioral activation? A review of the empirical literature.
AB  - Behavioral Activation (BA) for depression is an empirically supported
      psychotherapy with a long history dating back to the 1970s. To date there have
      been no systematic reviews of how BA treatment packages and their accompanying
      components have evolved over the years. This review sought to identify and
      describe the specific treatment components of BA based on the descriptions of
      techniques provided in empirical articles on BA and referenced treatment manuals
      when available. The following component techniques were identified: activity
      monitoring, assessment of life goals and values, activity scheduling, skills
      training, relaxation training, contingency management, procedures targeting
      verbal behavior, and procedures targeting avoidance. The implementation of these
      techniques is reviewed, along with their empirical support both as stand-alone
      components and as components of larger treatment packages. Whereas activity
      scheduling, relaxation, and skills training interventions have received empirical
      support on their own, other procedures have shown effectiveness as parts of
      larger treatment packages. Although BA interventions differed in tools used,
      activity monitoring and scheduling were shown to be constant components across
      interventions. Possible directions for the future evolution of BA are discussed.

PMID- 20677370
TI  - Characteristics and epidemiology of zygomaticomaxillary complex fractures.
AB  - OBJECTIVES: The aim of this study was to analyze the characteristics, namely,
      cause, type, site of fracture, and epidemiology data, of zygomaticomaxillary
      complex (ZMC) fractures. MATERIALS AND METHODS: Hospital records and computed
      tomographic scans of 468 patients, treated for ZMC fractures at the Department of
      Craniomaxillofacial and Oncological Surgery between January 1990 and December
      1995 and between January 2000 and December 2007, were selected and analyzed
      according to several factors including age, sex, cause, type, site of fracture,
      alcohol use before injury treatment modalities, complications, and mean treatment
      delay. RESULTS: A total of 468 patients (400 males and 68 females; male to-female
      ratio, 5.88:1) were included in this study. Their ages ranged from 15 to 85 years
      (mean T SD age, 37.1 T 14.83 y). Type B, by Zingg classification, was the most
      common type of ZMC fractures and accounted for 73.1% of cases. Assaults (64.5%),
      traffic accidents (13.9%), falls (13.0%), sports accidents (5.8%), and work
      accidents (2.8%) were noted. More than one-third of all the patients experienced
      injury after alcohol consumption. Of these patients, 96.6% were treated
      surgically. The most favored technique was miniplate osteosynthesis. The
      complication rate associated with the inaccurate reduction of the fractures was
      the most common. In this group of complications, minor asymmetry was the most
      common and occurred in 35 patients. Mean treatment delay was 42.7 hours. It
      ranged from 0.25 to 1080 hours, and the lowest value was observed in work
      accidents (2.7 hours). CONCLUSIONS: Facial trauma can result in fractures limited
      to 1 component of the tetrapod structure but more commonly results in a tetrapod
      fracture involving all 4 buttresses. Males are the most common victims of ZMC
      fractures, and assault remains the major cause of ZMC injuries in Poland, like in
      most developed countries. Alcohol involvement among trauma patients is high,
      especially in case of assaults and falls. Each patient with ZMC fracture should
      be evaluated individually.

PMID- 20677371
TI  - Staffing ratios hinder patient care.

PMID- 20677372
TI  - Regional cerebral glucose uptake in the 3xTG model of Alzheimer's disease
      highlights common regional vulnerability across AD mouse models.
AB  - We have previously used fluorodeoxyglucose (FDG) autoradiography to detect the
      pattern of metabolic declines in two different transgenic mouse models of
      fibrillar beta-amyloid pathology in Alzheimer's disease (AD), including the PDAPP
      mouse, which overexpresses a mutant form of human APP, and the PSAPP mouse, which
      overexpresses mutant forms of the human APP and PS1 genes. In this study, we used
      the same approach to study a triple-transgenic (3xTG) model of AD, which
      overexpresses human APP, PS1 and tau mutations, and progressively develops
      amyloid plaques, neurofibrillary tangles, and synaptic dysfunction. Densitometric
      measurements from 55 brain regions were characterized and compared in 2, 12, and
      18 month-old 3xTG and wildtype control mice (n = 12/group). By 18 months of age,
      the 3xTG mice had significant reductions in FDG uptake in every measured brain
      region, including cortical and subcortical gray matter, cerebellar and brainstem
      regions. However, regional differences in normalized FDG uptake were apparent in
      the 2- and 12-month-old 3xTG mice, in a brain network pattern reminiscent of our
      previous analyses in the other mouse models. This prominently included the
      posterior cingulate/retrosplenial cortex, as in each previously-analyzed model.
      Overall, our analyses highlight consistencies in brain glucose uptake
      abnormalities across multiple mouse models of amyloid-associated pathophysiology.
      These mouse brain regional changes are homologous to alterations seen in PET
      scans from human AD patients and could thus be useful biomarkers for early
      testing of novel interventions.

PMID- 20677374
TI  - ATDB 2.0: A database integrated toxin-ion channel interaction data.
AB  - We have developed an updated version of the Animal Toxin Database (ATDB 2.0) that
      provides a new bioinformatics resource for analyzing toxin-channel (T-C)
      interactions. Data on more than 54,000 T-C interactions, including 9193 high
      confidence interactions, has been extracted, formatted and mapped to toxin and
      ion channel databases. The interaction data can be accessed easily through a new
      network browser on the website at http://protchem.hunnu.edu.cn/toxin. This
      resource may be useful for sequence pattern recognition and prediction of the
      function of new toxins.

PMID- 20677373
TI  - Comparative study of anticoagulant and procoagulant properties of 28 snake venoms
      from families Elapidae, Viperidae, and purified Russell's  viper venom-factor X
      activator (RVV-X).
AB  - Snake venoms consist of numerous molecules with diverse biological functions used
      for capturing prey. Each component of venom has a specific target, and alters the
      biological function of its target. Once these molecules are identified,
      characterized, and cloned; they could have medical applications. The activated
      clotting time (ACT) and clot rate were used for screening procoagulant and
      anticoagulant properties of 28 snake venoms. Crude venoms from Daboia russellii
      siamensis, Bothrops asper, Bothrops moojeni, and one Crotalus oreganus helleri
      from Wrightwood, CA, had procoagulant activity. These venoms induced a
      significant shortening of the ACT and showed a significant increase in the clot
      rate when compared to the negative control. Factor X activator activity was also
      measured in 28 venoms, and D. r. siamensis venom was 5-6 times higher than those
      of B. asper, B. moojeni, and C. o. helleri from Wrightwood County. Russell's
      viper venom-factor X activator (RVV-X) was purified from D. r. siamensis venom,
      and then procoagulant activity was evaluated by the ACT and clot rate. Other
      venoms, Crotalus atrox and two Naja pallida, had anticoagulant activity. A
      significant increase in the ACT and a significant decrease in the clot rate were
      observed after the addition of these venoms; therefore, the venoms were
      considered to have anticoagulant activity. Venoms from the same species did not
      always have the same ACT and clot rate profiles, but the profiles were an
      excellent way to identify procoagulant and anticoagulant activities in snake
      venoms.

PMID- 20677376
TI  - Connectivity-based segmentation of the substantia nigra in human and its
      implications in Parkinson's disease.
AB  - The aims of this study were to i) identify substantia nigra subregions i.e. pars
      reticulata (SNr) and pars compacta (SNc), in human, and ii) to assess volumetric
      changes in these subregions in the diagnosis of Parkinson's disease. Current MR
      imaging techniques are unable to distinguish SNr and SNc. Segmentation of these
      regions may be clinically useful in Parkinson's disease (PD) as substantia nigra
      is invariably affected in PD. We acquired quantitative T1 as well as diffusion
      tensor imaging (DTI) data from ten healthy subjects and ten PD patients. For each
      subject, the left and right SN were manually outlined on T1 images and then
      classified into two discrete regions based on the characteristics of their
      connectivity with the rest of the brain using an automated clustering method on
      the DTI data. We identified two regions in each subjects' SN: an internal region
      that is likely to correspond with SNc because it was mainly connected with
      posterior striatum, pallidum, anterior thalamus, and prefrontal cortex; and an
      external region that corresponds with SNr because it was chiefly connected with
      posterior thalamus, ventral thalamus, and motor cortex. Volumetric study of these
      regions in PD patients showed a general atrophy in PD particularly in the right
      SNr. This pilot study showed that automated DTI-based parcellation of SN
      subregions may provide a useful tool for in-vivo identification of SNc and SNr
      and might therefore assist to detect changes that occur in patients with PD.

PMID- 20677375
TI  - Age-specific effects of 6-hydroxydopamine lesions of the rat medial  prefrontal
      cortex on stress-induced c-fos expression in subcortical  areas.
AB  - As adolescence is a critical period when dopaminergic neuronal maturation peaks,
      we hypothesized that 6-hydroxydopamine (OHDA) lesions of the medial prefrontal
      cortex (mPFC) in adolescent rats would have more negative effects than lesions in
      adult rats. Therefore, we investigated the effects of 6-OHDA lesions of the mPFC
      in adolescent and adult rats on stress-induced c-fos expression in the brain.
      Adolescent and adult Sprague-Dawley rats, aged 4 and 7 weeks on arrival,
      respectively, were studied. 6-OHDA (8.0 microg) for the lesion groups and
      ascorbic acid for the sham groups were injected bilaterally into the mPFC. All
      animals were pretreated with desipramine 30 min before being anesthetized. The
      control group did not undergo any surgery-related procedure except the
      desipramine injection. After recovery for 1 week, the rats were subjected to
      restraint stress for 1 h. Immediately after the stress, the rats were killed and
      c-fos immunohistochemistry was examined. The c-fos expression in the nucleus
      accumbens core (AcbC), nucleus accumbens shell (AcbSh), CA1, CA3, dentate gyrus
      (DG), central amygdaloid (Ce), basolateral amygdaloid (BL), and temporal cortex
      (Tc) was compared. Adolescent rats with 6-OHDA lesions subjected to restraint
      stress had greater c-fos expression in the AcbC, AcbSh, DG, Ce, BL, and Tc,
      compared to the sham and control groups, whereas these differences were not
      observed among the adult groups. These results suggest that a hypodopaminergic
      state in the mPFC of adolescent rats, but not adult rats, is related to increased
      sensitivity to stress, suggesting that damage to or maldevelopment of
      dopaminergic neurons during adolescence has an age-specific effect. Further
      research is warranted to investigate the mechanism of the age-specific effect of
      6-OHDA lesions of the mPFC.

PMID- 20677377
TI  - Persistent posterior and transient anterior medial temporal lobe activity during
      navigation.
AB  - A functional segregation along the posterior-anterior axis of the medial temporal
      lobe (MTL) has been suggested. In brief, it is thought that the posterior
      hippocampus represents environmental detail and/or encodes space, whereas the
      anterior part represents the environment more as a whole and/or subserves
      behavior. Different phases of navigation should thus recruit different structures
      within the MTL. Based on animal studies and neuroimaging data from humans, the
      initial phase of navigation, i.e., self-localization, target localization and
      path planning, should depend on the anterior MTL independent of upcoming
      navigational demands, whereas posterior MTL should be active throughout
      navigation. We tested this prediction using fMRI with navigation in a learned
      large-scale virtual office landscape with numerous complex landmarks under
      different navigational conditions. The initial navigational phase specifically
      engaged the anterior MTL. Increased activity was found bilaterally in the rostral
      and caudal entorhinal cortex. This is, to our knowledge, the first report of
      entorhinal activity in virtual navigation detected in a direct comparison. Also
      bilateral anterior hippocampus and anterior parahippocampal cortex were
      significantly more active during the initial phase. Activity lasting throughout
      the navigational period was found in the right posterior hippocampus and
      parahippocampal cortex. Hippocampal activity for the entire navigation period was
      only detected when the virtual environment remained unaltered. Navigational
      success was positively correlated with activity in the anterior right hippocampus
      for the initial phase, and more posteriorly in the hippocampus for the whole
      navigation period. Plots of the BOLD signal time course demonstrated that
      activity in the anterior hippocampus was transient whereas activity in the
      posterior hippocampus peaked regularly throughout the entire navigation period.
      These results support a functional segregation within the MTL with regard to
      navigational phases. The anterior MTL appears to complete associations related to
      the environment at large and provide a behavioral plan for navigation, whereas
      the posterior part keeps track of current location.

PMID- 20677378
TI  - [Perioperative anaesthetic practices in liver transplantation in France:
      Evolution between 2004 and 2008].
AB  - OBJECTIVES: To determine the evolution of French perioperative anaesthetic
      practices in liver transplantation between 2004 and 2008. STUDY DESIGN: Phone
      survey. METHODS: In 2004 and 2008, a similar questionnaire has been administered
      by phone to a senior anaesthesiologist from each French centre performing adult
      liver transplantation (n = 21). Results were compared using Fisher test and p <
      0.05 was considered significant. RESULTS: Between 2004 and 2008, there was a
      trend towards an increase of centres performing transplantation for more than 40%
      of Child C patients (p = 0.1). Simultaneously, work force dedicated to liver
      transplantation cases has been reduced since in 2008, one anaesthesiologist was
      in charge in 90% of the centres (p = 0.06 vs 2004). Perioperative practices
      remained largely heterogeneous between centres with regard to hemodynamic
      monitoring, fluid and blood products management, antifibrinolytics use or
      postoperative analgesia. CONCLUSIONS: This French survey has shown a reduction of
      work force dedicated to a liver transplantation from 2004 to 2008 simultaneously
      with a trend towards a greater severity of liver recipients. Practices
      heterogeneity reflect at least in part, unresolved questions about the best
      perioperative management for liver transplantation and the need for guidelines.
      Working for standardization of our practices and multicentric trials could allow
      gaining a better understanding of what should be the good practices in
      perioperative management of liver transplantation.

PMID- 20677379
TI  - The iPad: gadget or medical godsend?

PMID- 20677380
TI  - Tackling tensions and ambivalences: Armenian girls' diasporic identities in
      Russia.
AB  - Research on diasporic youth identities in the British and American context has
      stressed hybridity, heterogeneity and multiplicity. This paper draws upon
      ethnographic research undertaken with Armenian girls to explore some of the
      tensions and ambivalences of negotiating diasporic identities in the Russian
      context. Diasporic identities are constructed through gender, and this paper
      illustrates how research participants negotiate their identities in relation to
      both belonging to the Armenian community and wider Russian society. At the same
      time, this paper examines how research participants draw differently on diasporic
      identifications in order to overcome tensions and ambivalences in their everyday
      lives. The paper shows that research participants are not inclined to reject
      their cultural roots in favor of new hybrid identities, but are able to recognize
      and appropriate different cultures in their identity negotiations.

PMID- 20677382
TI  - Family and nation: Cherokee orphan care, 1835-1903.

PMID- 20677383
TI  - The growth of the native american gaming industry: what has the past provided,
      and what does the future hold?

PMID- 20677385
TI  - The diabetic foot: managing infection using Cutimed Sorbact dressings.
AB  - Management of the diabetic foot is often problematic, particularly as the
      diabetic patient is prone to sub-clinical infections. This article reviews
      diabetic foot ulceration and its treatment and describes some of the commonly
      associated complications of these chronic wounds. It is proposed that highly
      hydrophobic dressings are of value in reducing the bacterial colonization of
      ulcers, and an excellent alternative to more commonly-prescribed, topical
      antimicrobial dressings, particularly those containing silver.

PMID- 20677386
TI  - "Scientia divinorum": anatomy, transmutation, and incorporation in Catharina von
      Greiffenberg's meditations on the incarnation and the gestation of Christ.

PMID- 20677387
TI  - "Fragrant wedding roses": Lutheran wedding sermons and gender definition in early
      modern Germany.

PMID- 20677388
TI  - Barrie Russell Jones.  1921-2009.

PMID- 20677389
TI  - Tales of seduction, tales of violence: argumentative strategies before the Basel
      marriage court.

PMID- 20677390
TI  - The mill at Bluntau: a family of poachers in the late eighteenth-century Salzburg
      countryside.

PMID- 20677391
TI  - Women as historians: the case of early modern German convents.

PMID- 20677392
TI  - Out of time.

PMID- 20677393
TI  - Teaching pelvic examinations under anaesthesia: what do women think?

PMID- 20677394
TI  - Innocence and the language of the body in discourses of the "Jahrhundertwende".

PMID- 20677395
TI  - From "Ideendichtung" to the "commercium mentis et corporis": the body in German
      literature around 1800.

PMID- 20677396
TI  - The discreet charm of the Belvedere: submerged homosexuality in eighteenth
      century writing on art.

PMID- 20677397
TI  - [Glass breast, readable heart: a psychopathographical topos in    the context of
      physiognomic tyranny in the writings of C. H. Spiess and  others].

PMID- 20677398
TI  - Diagnosis and treatment of temporomandibular disorders: emergence of a new
      "standard of care".

PMID- 20677399
TI  - [Helicobacter pylori resistance].

PMID- 20677400
TI  - [Goodbye to Ugeskriftet].

PMID- 20677402
TI  - Current status of human papillomavirus vaccines.

PMID- 20677403
TI  - Adipose tissue development. From animal models to clinical conditions.

PMID- 20677404
TI  - Female illness and male heroism: the works of Caroline von Wolzogen.

PMID- 20677406
TI  - Welfare, democracy, and fascism: the political crises in German child welfare,
      1922-1933.

PMID- 20677409
TI  - Women and the Affordable Care Act of 2010.
AB  - This issue brief analyzes how, over the next decade, the Affordable Care Act
      (ACA) is likely to stabilize and reverse women's growing exposure to health care
      costs. Up to 15 million women who now are uninsured could gain subsidized
      coverage under the law. In addition, 14.5 million insured women will benefit from
      provisions that improve coverage or reduce premiums. Women who have coverage
      through the individual insurance market and are charged higher premiums than men,
      who have been unable to secure coverage for the cost of pregnancy, or who have a
      preexisting health condition excluded from their benefits will ultimately find
      themselves on a level playing field with men, enjoying a full range of
      comprehensive benefits.

PMID- 20677410
TI  - [Pomeranian nobility in the course of the 19th century].

PMID- 20677411
TI  - [Landed aristocracy and the rural middle class:    Mecklenburg-Strelitz and Upper
      Swabia, 1750-1850].

PMID- 20677412
TI  - [The introduction of the metric system in Dutch medicine,    1820-80].

PMID- 20677413
TI  - Position of the American Dietetic Association: local support for nutrition
      integrity in schools.
AB  - It is the position of the American Dietetic Association (ADA) that schools and
      communities have a shared responsibility to provide students with access to high
      quality, affordable, nutritious foods and beverages. School-based nutrition
      services, including the provision of meals through the National School Lunch
      Program and the School Breakfast Program, are an integral part of the total
      education program. Strong wellness policies promote environments that enhance
      nutrition integrity and help students to develop lifelong healthy behaviors. ADA
      actively supported the 2004 and proposed 2010 Child Nutrition reauthorization
      which determines school nutrition policy. ADA believes that the Dietary
      Guidelines for Americans should serve as the foundation for all food and
      nutrition assistance programs and should apply to all foods and beverages sold or
      served to students during the school day. Local wellness policies are mandated by
      federal legislation for all school districts participating in the National School
      Lunch Program. These policies support nutrition integrity,including a healthy
      school environment. Nutrition integrity also requires coordinating nutrition
      education and promotion and funding research on program outcomes. Registered
      dietitians and dietetic technicians, registered, and other credentialed staff,
      are essential for nutrition integrity in schools to perform in policy-making,
      management, education, and community building roles. A healthy school environment
      can be achieved through adequate funding of school meals programs and through
      implementation and evaluation of strong local wellness policies.

PMID- 20677414
TI  - [Laqueur and organon: the university laboratory and the pharmaceutical industry
      in the Netherlands].

PMID- 20677415
TI  - Medicare and Medicaid programs; electronic health record incentive program. Final
      rule.
AB  - This final rule implements the provisions of the American Recovery and
      Reinvestment Act of 2009 (ARRA) (Pub. L. 111-5) that provide incentive payments
      to eligible professionals (EPs), eligible hospitals and critical access hospitals
      (CAHs) participating in Medicare and Medicaid programs that adopt and
      successfully demonstrate meaningful use of certified electronic health record
      (EHR) technology. This final rule specifies--the initial criteria EPs, eligible
      hospitals, and CAHs must meet in order to qualify for an incentive payment;
      calculation of the incentive payment amounts; payment adjustments under Medicare
      for covered professional services and inpatient hospital services provided by
      EPs, eligible hospitals and CAHs failing to demonstrate meaningful use of
      certified EHR technology; and other program participation requirements. Also, the
      Office of the National Coordinator for Health Information Technology (ONC) will
      be issuing a closely related final rule that specifies the Secretary's adoption
      of an initial set of standards, implementation, specifications, and certification
      criteria for electronic health records. ONC has also issued a separate final rule
      on the establishment of certification programs for health information technology.

PMID- 20677416
TI  - Health information technology: initial set of standards, implementation
      specifications, and certification criteria for electronic health record
      technology. Final rule.
AB  - The Department of Health and Human Services (HHS) is issuing this final rule to
      complete the adoption of an initial set of standards, implementation
      specifications, and certification criteria, and to more closely align such
      standards, implementation specifications, and certification criteria with final
      meaningful use Stage 1 objectives and measures. Adopted certification criteria
      establish the required capabilities and specify the related standards and
      implementation specifications that certified electronic health record (EHR)
      technology will need to include to, at a minimum, support the achievement of
      meaningful use Stage 1 by eligible professionals, eligible hospitals, and/or
      critical access hospitals (hereafter, references to "eligible hospitals" in this
      final rule shall mean "eligible hospitals and/or critical access hospitals")
      under the Medicare and Medicaid EHR Incentive Programs. Complete EHRs and EHR
      Modules will be tested and certified according to adopted certification criteria
      to ensure that they have properly implemented adopted standards and
      implementation specifications and otherwise comply with the adopted certification
      criteria.

PMID- 20677417
TI  - Pre-existing condition insurance plan program. Interim final rule with comment
      period.
AB  - Section 1101 of Title I of the Patient Protection and Affordable Care Act of 2010
      (Affordable Care Act) requires that the Secretary establish, either directly or
      through contracts with States or nonprofit private entities, a temporary high
      risk health insurance pool program to provide affordable health insurance
      coverage to uninsured individuals with pre-existing conditions. This program will
      continue until January 1, 2014, when Exchanges established under sections 1311
      and 1321 of the Affordable Care Act will be available for individuals to obtain
      health insurance coverage. This interim final rule implements requirements in
      section 1101 of the Affordable Care Act. Key issues addressed in this interim
      final rule include administration of the program, eligibility and enrollment,
      benefits, premiums, funding, and appeals and oversight rules.

PMID- 20677418
TI  - Surveillance of Creutzfeldt-Jakob disease in Australia: 2010 update.
AB  - Surveillance of all human prion diseases in Australia has been the responsibility
      of the Australian National Creutzfeldt-Jakob Disease Registry (ANCJDR) on behalf
      of the Australian Government Department of Health and Ageing since the Registry's
      inception in October 1993. The ANCJDR was established in response to the
      identification of 4 CJD deaths in recipients of human-derived pituitary hormone.
      The initial brief was to perform focused surveillance for any further iatrogenic
      cases of CJD; however the scope of surveillance was soon expanded to include all
      cases of CJD occurring in Australia both prospectively and retrospectively to
      1970. The activities of the ANCJDR have evolved from: routine surveillance
      responsibilities to detailed epidemiological analysis at both national and
      international levels; expert advice in relation to, and management of, infection
      control issues; and the provision of a number of tests to aid the diagnosis and
      classification of CJD in suspect cases. In this brief report, surveillance
      outcomes are examined with the inclusion of figures from the reporting period of
      1 April 2009 to 31 March 2010 and the diagnostic services offered by the ANCJDR
      are outlined to provide a greater insight into this aspect of the Registry.

PMID- 20677419
TI  - Pandemic influenza H1N1 2009 in north Queensland--risk factors for admission in a
      region with a large indigenous population.
AB  - This study describes the epidemiology of laboratory-confirmed pandemic influenza
      H1N1 within north Queensland, Australia. We collected data on all specimens
      tested for influenza (including H1N1) by polymerase chain reaction between May
      and August 2009 at Townsville Hospital. Patients requiring admission to hospital
      and a proportion of non-admitted patients had clinical characteristics recorded.
      Multi-variable logistic regression analysis was used to identify independent
      predictors for admission. Patients requiring admission were on average older,
      less likely to be of Aboriginal or Torres Strait Islander descent and more likely
      to be pregnant, female or suffer from diabetes mellitus. Oseltamivir provision
      was significantly higher within the Aboriginal or Torres Strait Islander patient
      population. However, when the relative sizes of the local Indigenous and non
      Indigenous populations were considered, the relative risk of hospital admission
      for Indigenous people was found to be 7.9 (4.7-13.2) in comparison to non
      indigenous.

PMID- 20677420
TI  - Evaluation of Campylobacter infection surveillance in Victoria.
AB  - Campylobacter infection is a notifiable infectious disease in Victoria and with
      more than 6,000 cases notified annually, it is the second most commonly notified
      disease after chlamydia. The objectives of Campylobacter infection surveillance
      in Victoria are to monitor the epidemiology of Campylobacter infection, identify
      outbreaks, initiate control and prevention actions, educate the public in disease
      prevention, evaluate control and prevention measures, and plan services and
      priority setting. An evaluation of the system was undertaken to assess
      performance against its objectives, identify areas requiring improvement and
      inform a decision of whether Campylobacter infection should remain a notifiable
      infectious disease. The surveillance system was assessed on the attributes of
      data quality, timeliness, simplicity and acceptability using notifiable
      infectious diseases data and interviews with doctors who had failed to notify,
      and laboratory and public health staff. The evaluation found that the system
      collects core demographic data with high completeness that are appropriately
      reviewed, analysed and reported. In 2007, 12% of Campylobacter isolates were
      subtyped and only one to 3 outbreaks were identified annually from 2002 to 2007.
      Fifty-four per cent of cases were notified by doctors and 96% by laboratories,
      although nearly half of laboratory notifications were not received within the
      prescribed timeframe. Half of the surveyed non-notifying doctors thought that
      Campylobacter infection was not serious enough to warrant notification. The
      Campylobacter surveillance system is not fully satisfying its objectives.
      Investment in the further development of analytical methods, electronic
      notification and Campylobacter subtyping is required to improve simplicity,
      acceptability, timeliness and sensitivity.

PMID- 20677421
TI  - Who gives pertussis to infants? Source of infection for laboratory confirmed
      cases less than 12 months of age during an epidemic, Sydney, 2009.
AB  - An important approach to protecting infants against pertussis is to provide a
      booster vaccination to close contacts, however this strategy requires a good
      understanding of infection sources to be effective. The objective of this study
      was to identify the most important sources of transmission of pertussis infection
      to infants, regardless of hospitalisation status. Standardised interviews were
      conducted during routine follow-up calls with the parent or guardian of
      laboratory confirmed pertussis cases less than 12 months of age notified to 3
      Sydney metropolitan public health units during a pertussis outbreak from January
      to May 2009. All contacts with a coughing illness or laboratory confirmed
      pertussis during the 3 weeks prior to onset of illness in the index case, were
      recorded. A source of infection could not be identified for 29 infants (31%) and
      a total of 86 known or suspected sources were identified for the other 66
      infants. The most frequently identified sources were siblings (36%) and parents
      (24%), followed by other family members (21%), friends (13%), and settings
      outside the home such as medical centres (6%). Of 20 siblings aged 3 or 4 years,
      16 (80%) were sources of infection, compared with 14 of the 44 (32%) other
      siblings less than 18 years of age. During this epidemic siblings were more
      important sources of infant infection than parents. Siblings aged 3 and 4 years
      of age were particularly important transmitters of pertussis infection to
      infants. Minimising pertussis infection in 3 and 4 year olds may be an important
      measure to prevent infant infection.

PMID- 20677422
TI  - Serotype 6C invasive pneumococcal disease in indigenous people in north
      Queensland.

PMID- 20677423
TI  - An outbreak of Salmonella Litchfield on a car rally, Northern Territory, 2009.

PMID- 20677424
TI  - Communicable diseases surveillance.

PMID- 20677425
TI  - [Exposure to bioaerosols among CAFO workers (swine feeding)].
AB  - BACKGROUND: In this paper the exposure assessment to airborne biohazards (organic
      dust, microorganisms, endotoxins and ((1 --> 3)-beta-D-glucans) as well as to
      ammonia and hydrogen sulfide among CAFO (swine farms) workers is presented.
      MATERIALS AND METHODS: Occupational exposure assessment was carried out on 30
      swine farms. Personal dosimetry was carried out among 90 swine farm workers to
      assess the exposure to organic dust, endotoxins and glucans. Concentrations of
      ammonia and hydrogen sulfide were measured using Draeger pipes. Endotoxins were
      assayed with the LAL test in a kinetic, chromogenic version and ((1 --> 3)-beta-D
      glucans with the Glucatell test in a kinetic version. RESULTS: Concentrations of
      inhalable dust ranged from 0.16 to 37.2 mg/m3, with AM = 3.65 mg/m3, whereas AM
      for respirable fraction was 0.39 mg/m3 with the range from zero to 4.28 mg/m3.
      Mean concentration of culturable bacteria was 4.79 x 10 (5) jtk/m3, and fungi
      concentration was ten times lower - 1.55 x 10(4) jtk/m3. Exposure to endotoxins
      with high degree of differentiation ranged from 95 to 147 885 EU/m3 in inhalable
      and from 5.5 to 18 708 EU/m3 in respirable fractions. Glucan concentrations
      ranged from 6 to > 5200 ng/m3 in unhalable and from 1 to 800 ng/m3 in respirable
      fraction. Ammonia concentrations in the workplace air ranged from 1.78 mg/m3
      (2.50 ppm) to 30.1 mg/m3 (42.4 ppm). Hydrogen sulfide did not exceed the level of
      4.1 mg/m3. CONCLUSION: Work conditions found in CAFOs may induce adverse effects
      on workers' respiratory system and should be considered as an important harmful
      agent. The protection of workers respiratory airways should be recommended.

PMID- 20677426
TI  - [Knowledge of toxoplasmosis among pregnant women, midwifes, medical students and
      obstetricians].
AB  - BACKGROUND: Knowledge of toxoplasmosis has been assessed among obstetricians,
      medical students, midwifes and pregnant women. The aims of the study were as
      follows: 1) evaluation of intra- and inter-group variation in correct answers to
      the questions included in the questionnaire used as a study tool; 2) evaluation
      of inter-group variation in answers to specialist and non-specialist questions;
      and 3) intra-group evaluation of self-assessed difficulty in completing the
      questionnaire. MATERIALS AND METHODS: In the prospective study, 310 participants
      were included: 109 pregnant women, 116 midwifes 85 physicians (including 69
      specialists in OB/GYN) and 16 medical students. The anonymous questionnaire
      consisted of 26 questions, with four answers proposed for each question of which
      one was correct. RESULTS: There was no difference between correct answers among
      midwifes, physicians and medical students (p = 0.20), but the difference was
      found between the group of physicians and medical students and pregnant women as
      well as between midwifes and pregnant women (p < 0.001). Physicians, medical
      students and midwifes gave best answers to the non-specialist questions (p <
      0.001), and midwifes obtained higher scores than pregnant women (p < 0.001). The
      mean percentage of correct answers to the specialist questions was among pregnant
      women (29%) showing a high level of randomness. The best answers to the non
      specialist questions were found for physicians and midwifes (p = 0.93). However,
      there was a difference between the group of physicians and medical students and
      pregnant women and between midwifes and pregnant women in self-assessment of
      difficulty in completing the questionnaire (p < 0.001). CONCLUSIONS: Pregnant
      women assessed their knowledge of toxoplasmosis as least adequate, whereas
      midwifes, as most adequate. Pregnant women's knowledge about toxoplasmosis is
      poor. The group of physicians and medical students yielded evidently better score
      than pregnant women. There is a need for the improvement among prenatal care
      providers in both patient education and self-education.

PMID- 20677427
TI  - [Occupational satisfaction and quality of life in women aged 45-60 years in the
      Silesia voivodeship].
AB  - BACKGROUND: Quality of life is an important issue of public health. It becomes
      essential in the population of active workers, especially women who besides their
      occupational activity have to perform other important roles, such as care of
      their children or older parents. MATERIALS AND METHODS: The presented study is an
      attempt to answer the question on whether occupational activity, especially job
      satisfaction, provides better quality of live in the population of women aged 45
      60 years. RESULTS: The obtained results confirm that a better quality of live,
      measured by the status of physical and mental health, is characteristic of
      occupationally active women with a higher level of education, who also experience
      job satisfaction. Care of children or older parents has no impact on the decline
      of quality of life. CONCLUSIONS: The improvement of qualifications and
      occupational activity can contribute to a better quality of live in the
      population of women.

PMID- 20677428
TI  - [Exposure to silica dust in coal-mining. Analysis based on measurements made by
      industrial hygiene laboratories in Poland, 2001-2005].
AB  - BACKGROUND: Exposure to dust is associated with a number of activities of the
      mining industry at every stage of the output process. Crushing machines, paving
      loaders, drilling blast holes, loading and transportation of excavated material
      are the major sources of dust emissions. The purpose of this study was to assess
      occupational exposure to silica dust in the hard and brown coal mines in Poland.
      MATERIALS AND METHODS: Based on the measurements of inhalable and respirable dust
      concentrations, performed by industrial hygiene laboratories in various branches
      of Polish industry from 2001 to 2005, a detailed analysis of exposure to dust in
      the all operating coal mines was carried out, taking into account specific
      workposts. Measurements were made according to current standards; the Taverage
      dust concentrations, degree of dispersion, range of results and the percentage of
      measurements exceeding occupational hygiene standards by specific workposts were
      calculated. RESULTS: The highest concentrations of inhalable (8.25 mg/m3) and
      respirable (3.11 mg/m3) dusts and the highest percentage of exceedances (74%)
      were noted in workers of hard coal mines, employed directly in the mining
      process. In the brown coal mines, slightly lower concentrations were found, and
      the highest levels of both dust fractions were obtained for workers involved in
      the transportation of raw material (inhalable dust, 4.13 mg/m3 and respirable
      dust, 1.02 mg/m3). CONCLUSIONS: Exposure to dust in Polish coal mines is still a
      major problem of industrial hygiene and occupational medicine. Particularly high
      concentrations of dust, often exceeding the hygiene standards, were found in
      underground mines at workposts directly related to the output and transport of
      raw materials and machinery operation.

PMID- 20677429
TI  - [Environment of air-ions in ship cabins and possibility of its optimization].
AB  - BACKGROUND: Analyses show that the concentration of air-ions in ship cabins
      almost always remains at levels lower than the required norms. Therefore, in this
      study possibilities of complementing the deficit of these particles were
      examined. MATERIALS AND METHODS: The research was carried out in a laboratory
      using ionisers and metal pipes with proper parameters, and then in the
      ventilation ducts of ships. RESULTS: The study showed that we can achieve the
      needed levels of air-ions in ship cabins by installing single ionisers with the
      capacity of delivering about 1 mln ions/cm3 in proper sections of the ventilation
      ducts.

PMID- 20677430
TI  - [Application of predictive model to estimate concentrations of chemical
      substances in the work environment].
AB  - BACKGROUND: Based on the Estimation and Assessment of Substance Exposure (EASE)
      predictive model implemented into the European Union System for the Evaluation of
      Substances (EUSES 2.1.), the exposure to three chosen organic solvents: toluene,
      ethyl acetate and acetone was estimated and compared with the results of
      measurements in workplaces. MATERIAL AND METHODS: Prior to validation, the EASE
      model was pretested using three exposure scenarios. The scenarios differed in the
      decision tree of pattern of use. Five substances were chosen for the test: 1,4
      dioxane tert-methyl-butyl ether, diethylamine, 1,1,1-trichloroethane and
      bisphenol A. After testing the EASE model, the next step was the validation by
      estimating the exposure level and comparing it with the results of measurements
      in the workplace. We used the results of measurements of toluene, ethyl acetate
      and acetone concentrations in the work environment of a paint and lacquer
      factory, a shoe factory and a refinery. Three types of exposure scenarios,
      adaptable to the description of working conditions were chosen to estimate
      inhalation exposure. RESULTS: Comparison of calculated exposure to toluene, ethyl
      acetate and acetone with measurements in workplaces showed that model predictions
      are comparable with the measurement results. Only for low concentration ranges,
      the measured concentrations were higher than those predicted. CONCLUSIONS: EASE
      is a clear, consistent system, which can be successfully used as an additional
      component of inhalation exposure estimation. If the measurement data are
      available, they should be preferred to values estimated from models. In addition
      to inhalation exposure estimation, the EASE model makes it possible not only to
      assess exposure-related risk but also to predict workers' dermal exposure.

PMID- 20677431
TI  - [Occupational exposure to HIV in health care workers, Silesia voivodeship].
AB  - BACKGROUND: Occupational exposure to HIV is defined as a contact of health care
      workers with potentially infectious material. The risk of occupational
      transmission is not high (0.09-0.3%), but it increases in case of percutaneous
      injuries caused by tools contaminated with infected blood, deep needle stick or
      direct contact of an infected needle with artery or vein. MATERIAL AND METHODS:
      The aim of the study was to determine the epidemiology of HIV infections among
      health care workers in the Silesian voivodeship, in the years 1999-2006 and the
      conditions of occupational exposure. Data on occupational exposure, collected by
      the Center for AIDS Diagnosis and Therapy in Chorzow, were analyzed. RESULTS:
      During the study period, 789 cases of occupational exposure to HIV in the medical
      staff were documented. In the exposed group women predominated (78.9%). In the
      occupational group under study, nurses made 65% and physicians 17.5%. Needles
      were the most frequent (75.2%) source of exposure during injections and left hand
      fingers (thumb and index finger) were the major targets. Post-exposure
      prophylaxis with antiretroviral medications was introduced in about 60% of cases
      (499/789). No HIV transmission was registered. CONCLUSIONS: Nurses run the
      highest risk of occupational exposure to HIV, usually related with injections.
      There is a need to continue education in postexposure prophylaxis addressed to
      medical staff. The development of a standard questionnaire and its practical use
      could be very useful in monitoring occupational exposure.

PMID- 20677432
TI  - [Occupational hygiene and health hazards related to concentrated animal feeding
      operations (CAFOs)].
AB  - Emissions of harmful agents, inherent in the intensive production of pigs, create
      an important problem concerning the protection of workers' health. Concentration
      of many animals on relatively small areas contributes to high air contaminations
      inside swine confinement buildings. They are mostly induced by bioaerosols, such
      as organic dust, microorganisms, endotoxins, glucans and irritant gases. In view
      of the health care and safety of people employed in animal farming, it is crucial
      to conduct research involving a comprehensive evaluation of exposure to
      occupational hazards, indicating their level determinants and increasing the
      scientific information on dose-response relations. This article presents the
      review of the literature on the process of pig farming in Poland, including
      legislation, occupational hygiene and potential risk for the health of animal
      handling workers.

PMID- 20677433
TI  - [Safe usage of chemicals in European Union countries].
AB  - New legal provisions have changed the rules of production, import and use of
      chemicals in the European Union Member States. Chemical substances present on the
      common market are covered by registration duty. Manufacturers and importers of
      substances are obliged to ensure that the risk posed by a given substance is
      adequately controlled on each stage. Information on substances is to be
      transferred both downstream and upstream in a supply chain. Substances of very
      high concern are the subject of authorisation procedure and will be gradually
      replaced by their safer equivalents. Information on substances of very high
      concern is transferred to downstream users and consumers. The European Chemicals
      Agency (ECHA) and Member States Competent Authorities have been established.
      National Helpdesks on REACH are operating in Member States, giving help to
      enterprises and other stakeholders.

PMID- 20677434
TI  - [What do we know about psychosocial risk factors at work? Part I. Theoretical
      considerations].
AB  - A growing interest in the development and implementation of preventive programs
      at workplace has recently been observed. According to the modern model of
      occupational health protection, recognition, monitoring and elimination of any
      potential risks at work are obligatory. This means that occupational health
      prevention also addresses the issue of psychosocial risks at work. There is a
      need of common understanding what the psychosocial risks are and how they affect
      human functioning to prevent them adequately and effectively. The aim of the
      paper is to present the present knowledge of psychosocial factors at work in a
      systematic way.

PMID- 20677435
TI  - [Activities of voivodeship occupational medicine centers in workplace health
      promotion in 2008].
AB  - The paper aims to present the activities of the largest Voivodeship Occupational
      Medicine Centers (VOMCs) in Poland in the area of workplace health promotion in
      2008. It was compiled on the basis of written reports concerning these activities
      sent by the Centers to the Polish National Center for Workplace Health Promotion,
      Nofer Institute of Occupational Medicine, Lodz. Their analysis shows a greatly
      varied level of engagement in and understanding of health promotion--from simple
      single actions (in the field of health education and screening) to long-running
      programs, including various ways of influencing people the programs are addressed
      to. In 2008, there were 78 such programs in the country, the most popular of them
      were those focused on occupational voice disorders and tobacco smoke). VOMCs
      perceive external factors, unfavorable or indifferent attitudes towards promoting
      health of their employees on the part of employers as well as financial
      constraints, as the most common obstacles in undertaking activities in the field
      of workplace health promotion. At the same time, they link achievements in this
      field mostly with their own activities, including effective cooperation with
      various partners and their well qualified and experienced employees.

PMID- 20677436
TI  - [Somatopsychic and cenesthetic types of schizophrenia: common features and
      discrepancies].
AB  - The aim of this paper is to discuss the development of the concepts of
      cenesthetic type of schizophrenia and somatopsychic type of schizophrenia along
      with the review of differences between those two diagnostic approaches in scope
      of their historical background and the current diagnostic concepts. Those
      independently described diagnostic phenomena have some common features. However,
      the cenesthetic type of schizophrenia emphasises sensory elements of the
      disorders and includes a broader spectrum of the psychopathology while the
      somatopsychic type of schizophrenia focuses on the thought disorders and strictly
      schizophrenic psychopathology.

PMID- 20677438
TI  - [Consistency of symptomatic dimensions of schizophrenia in a 12 year follow up
      study].
AB  - AIM: Objectives were to identify syndromes measured by BPRS-E scale and to
      analyse changes in syndromes' consistency in the course of a 12 year prospective
      study. METHOD: A group of 80 patients with diagnosis of schizophrenia was
      followed up in 1, 3, 7 and 12 years after their first psychiatric
      hospitalisation. Their psychopathological status was investigated with BPRS-E
      scale. RESULT: Four syndromes were found: positive, negative, depressive and
      excitement. However, in the following time points, consistency of syndromes was
      different. The most consistent syndrome was the negative one. Often symptoms
      connected with this syndrome four, namely: motor retardation, blunted affect,
      uncooperativeness, emotional withdrawal were present in every follow-up within
      this syndrome. In the case of the excitement syndrome two symptoms (hostility and
      tension) were present in all follow-ups. None of the symptoms included in the
      depressive and positive syndromes were consistently present within these
      syndromes over the period of twelve years.

PMID- 20677437
TI  - [The role of expressed emotions indicator as a predictor of the course of
      schizophrenia].
AB  - OBJECTIVE: The study is a part of a prospective schizophrenia research project
      run in Krak6w. The general objective of the project is a long-time observation of
      people with schizophrenia, starting from the first episode through the years of
      living with the illness, the assessment of treatment results and predictors. The
      goal of this study was to investigate whether the level of expressed emotions in
      family at the onset of schizophrenia may have a prognostic value in regard to the
      further course of the illness. METHOD: Four indicators of treatment results were
      observed: the number of relapses, the overall time of inpatient hospitalisations,
      the number of inpatient hospitalisations and the severity of psychopathological
      symptoms, all in 3, 7 and 12 years since first hospitalisations. Expressed
      emotions (EE) were assessed with Camberwell Family Interview (CFI), the severity
      of symptoms was assessed with BPRS-SA, the UCLA version. RESULTS: (1) The
      increase of the number of relapses in subsequent follow-ups was more pronounced
      in the group of subjects with higher EE at the time of their first
      hospitalisations. (2) The number and overall time of hospitalisations did not
      correspond in any way with the EE level at the time of the first hospitalisation.
      (3) The dynamics of general and positive symptoms was related to the EE level at
      the time of the first hospitalisation. The negative syndrome was found to have no
      significant relationships. CONCLUSIONS: (1) The level of EE at the time of the
      first hospitalisation can be regarded as a specific predictor of relapses in the
      study group. (2) Creating research models that enable to differentiate: trait and
      state as well as dependent on family and on the course of illness aspects of EE,
      would enable better understanding of this phenomenon, which appears both as
      predictor and as effect of the course of schizophrenia.

PMID- 20677439
TI  - [Lack of association between the insertion/deletion polymorphism in serotonin
      transporter gene, T102C polymorphism of the 5HT2A receptor gene and schizophrenia
      -family based study].
AB  - AIM: The aim of the study was to estimate the transmission of two candidate
      genes' alleles (according to the serotonergic hypothesis of schizophrenia) by
      parents to their children with schizophrenia. The genes under investigation were
      the following: 5HTR2A (polymorphism T102C) and SLC6A4 (polymorphism 5-HTTLPR).
      METHOD: There were 116 families in the group under investigation (patient and
      his/her both parents). Due to the missing genotypes or unlikely inheritance
      (other biological parent or genotyping error) the number of analysed trios
      differs for particular polymorphisms (these trios were not excluded from the
      study, however they were not analysed in the case of a given polymorphism). The
      patients and their parents were examined using the SCID (Structured Clinical
      Interview for DSM-IV Axis I Disorders). No mental disorders were found with all
      the patients' parents. The DNA was extracted from the peripheral blood leukocytes
      by the salting out method. The polymorphisms were studied by the PCR method (PCR
      RFLP method for: 5HTR2A and PCR-VNTR method for: SLC6A4). The statistical
      analysis of the frequency of transmission of alleles was carried out by the TDT
      (Transmission Disequilibrium Test) method. To analyse the transmission
      disequilibrium of alleles under examination, the Haploview v. 3.2. programme was
      used. RESULTS: According to the results obtained, no association between the
      analysed polymorphism of genes: 5HTR2A (T102C), SLC6A4 (5-HTTLPR) and
      schizophrenia was found. CONCLUSIONS: Thus it seems advisable to carry out
      further examinations of the role of these polymorphisms in schizophrenia by means
      of TDT method and the classical association method.

PMID- 20677440
TI  - [Functional polymorphism of genes inactivating catecholamines and emotional
      deficits in paranoid schizophrenia].
AB  - AIM: The aim of our work was to assess qualitatively and quantatively emotional
      deficits in patients diagnosed with schizophrenia following ICD-10 criteria in
      early and late stages of the schizophrenic process and the evaluation of the
      relationship between genes polymorphism of enzymes influencing dopaminergic,
      serotoninergic, and noradrenergic transfer and emotional functioning of the
      examined patients. METHOD: In our study the following methods have been used:
      Short Recognition Memory test for Faces (TPRT), Facial Expression Recognition
      Test (FERT), "Reading the mind in the eyes" Test and psychiatric scales (SAPS,
      SANS, BDI) and molecular techniques (PCR reaction, RFLP and VNTR techniques). 100
      paranoid schizophrenia patients (43 female and 57 man) and 50 healthy controls
      (30 female and 20 man) were invited to participate in the study. RESULTS: Our
      results revealed an association between polymorphism of Val158Met COMT and
      emotional deficits in schizophrenic patients. Furthermore, the relationship
      between polymorphism of MAO-A and empathy/theory of mind deficit was found. No
      relationship was elicited between polymorphism of Val158Met COMT and VNTR MAO-A
      in the promoter area and schizophrenia onset. Allelic distribution of
      polymorphism of Val158Met COMT and VNTR MAO-A in the promoter area did not differ
      between the groups. The patients with genotype Val/Val of polymorphism Val158Met
      COMT showed major emotional deficits. The patients with genotype of 4/4 of
      polymorphism VNTR MAO-A showed deeper empathy/theory of mind deficits.

PMID- 20677441
TI  - [Neurobiological expression of the placebo effect].
AB  - Neurobiology of the placebo effect dates back to 1978, when Levine discovered
      that its analgesic action is reversed by naloxone. Since then, various studies
      have been performed to estimate the impact of placebo on brain metabolism and
      neurotransmission in analgesia, depression or the Parkinson's disease. A number
      of involved brain structures have been pinpointed, these including nucleus
      accumbens and the anterior cingulate cortex (ACC), while the role ofopioid
      regulation has been established as significant to the process. Currently, modern
      diagnostic appliances such as PET or fMRI are being used to determine the
      differences between placebo and drug effect on brain metabolism and,
      consequently, to identify factors responsible for therapeutic response and their
      potential correlation with a psychological impact. Environmental conditions,
      which may result in placebo efficacy increase of seven percent per decade during
      the last years, are also looked into. Although certain ethical and legal dilemmas
      appear considering the use of placebo, it is beyond any doubt that realising the
      influence of expectation and conditioning on the neurobiology of the placebo
      effect, as well as on the proper therapy, should enable better patient handling
      and treatment in the future.

PMID- 20677442
TI  - [Restless legs syndrome].
AB  - Restless legs syndrome (RLS) is characterised by daily dynamic sensorial and
      motor syndromes. It is a relatively little known syndrome among neurologists as
      well as psychiatrists. In spite of a growing number of researches on this issue,
      the problem seems to be underdiagnosed. Because of a subjective character of the
      symptoms and also their appearance in the evening hours, they are difficult to
      observe among outpatients. In the case of diagnosing the restless legs syndrome,
      therapists pay attention to sleep disorders, which usually remain as the only one
      being treated and others are omitted. Some are convinced of little harmfulness of
      this syndrome, however sleep disorders themselves worsen social functioning and
      those disorders lasting longer, increase the probability of other, not only
      psychiatric disorders appearing. A separate issue is the not yet established
      pathogenesis of the restlessness legs syndrome, especially its genetic
      background. It is important because of the possible ways of treatment.
      Undoubtedly RLS needs more research and promoting knowledge on this issue not
      only among doctors but also in the whole society.

PMID- 20677443
TI  - [Munchausen syndrome by proxy].
AB  - Munchausen syndrome by proxy (MSBP), is a psychiatric disorder, a particular form
      of child abuse. An impaired emotional relationship exists mainly between the
      mother and her child. According to the variety of victims' symptoms, all medicine
      doctors may deal with this syndrome in every day clinical practice. Still
      insufficient knowledge about the syndrome and its' rare consideration in the
      differential diagnosis result in only severe, potentially lethal cases
      recognition. For many years the rest remains a source of a long-term physical and
      mental injuries in victims. About 30 years from the first attempt to precisely
      point the signalling symptoms for a proper diagnosis, we present the current
      knowledge on epidemiology, aetiology, diagnostic criteria, advised management and
      psychological portrait of the mother with the syndrome and her child, the
      syndrome's victim.

PMID- 20677444
TI  - [Patients' opinions on services provided in psychiatric and neurological wards--a
      comparison].
AB  - AIM: To compare patients' opinions about services in psychiatric and neurological
      wards in the years 2005 and 2007. METHOD: In 2005, 272 responders from
      psychiatric wards and 245 neurological ones and in 2007, 370 and 233 responders
      respectively answered the In-Patient's Opinion Questionnaire anonymously.
      RESULTS: Both groups regarded staff politeness, kindness, patience and
      friendliness as the most positive element of hospitalisation. Responders from
      psychiatry most often complain about in-patient specifics; from neurology about
      the stay conditions. Comparison of patients' opinions from psychiatry in 2005 and
      2007 year indicates stability of positive opinions in majority of areas; the
      second study shows the essential growth of positive opinions in neurological
      wards. In both groups, satisfaction regarding information accessibility, form of
      contact with staff (less satisfying in neurological wards) and emotional support
      is still too low. Persons' percentage confirming emotional support from staff is
      higher in psychiatric wards than neurological ones in both studies. CONCLUSIONS:
      Staff friendliness plays a very important role during the hospitalisation. Both
      groups indicate dimensions requiring improvement: access to information, form of
      contact with staff, emotional support. The resultsindicate a contrast between the
      system of support on psychiatric wards and lack of this on the neurological ones.
      The neurological wards can use psychiatric ward positive experience regarding
      patients' emotional support received from nurses and the building staff patients
      relationship based on ideas of the therapeutic community. The changes in medical
      care between 2005 and 2007 had no effect on the quality of services in both kinds
      of wards. Progress of quality in psychiatric and neurological wards requires
      structural changes in medical care.

PMID- 20677445
TI  - [Body image among obese women: consequences and degree of body dissatisfaction,
      relationship with low self-esteem and coping strategies].
AB  - AIM: Definition of factors influencing negative body image among obese women and
      analysis of the relationship between body dissatisfaction and personality
      variables. METHOD: 63 patients participated in this study. The mean age of the
      obese subjects was 41.90 years (SD +/- 12.23) and the mean body mass index (BMI)
      was 37.09 kg/m2 (SD +/- 8.09). The control group consisted of 60 women with
      normal body weight. The Body Dissatisfaction Scale of EDI (Garner et al., 1984),
      the Self-Esteem Inventory (Coopersmith, 1983) and the Brief COPE (Carver, 1997)
      were used in the study. RESULTS: In the clinical sample of women suffering from
      obesity, we have found a correlation between body dissatisfaction and behavioural
      disengagement, four dimensions of self-esteem (general, social, family and
      professional) and coping strategies focused on planning and positive
      reinterpretation. The regression analysis revealed that use of emotional support,
      planning and general self-esteem were predictive factors for the body
      dissatisfaction in obesity. CONCLUSION: Body dissatisfaction seriously influences
      the social, professional and emotional obese women's self.

PMID- 20677446
TI  - [Menstrual dysfunction in anorexia nervosa].
AB  - One of the symptoms of anorexia nervosa (a.n.) is cessation of pubescence or
      secondary amenorrhea. Their origin in anorexia nervosa is multifactorial, partly
      resulting from starvation-induced hipogonadism. Amenorrhea in a.n. may persist
      despite weight recovery and is often related to osteoporosis. The authors'
      present causes of amenorrhea and its persisting in a.n., pointing to the factors
      influencing prognosis according to resumption of menses. They also review reports
      of hormonal replacement therapy in this group of patients.

PMID- 20677448
TI  - [Thurstone model application to difference sensory tests].
AB  - Part of understanding why judges perform better on some difference tests than
      others requires an understanding of how information coming from the mouth to the
      brain is processed. For some tests it is processed more efficiently than others.
      This is described by what has been called Thurstonian modeling. This brief review
      introduces the concepts and ideas involved in Thurstonian modeling as applied to
      sensory difference measurement. It summarizes the literature concerned with the
      theorizing and confirmation of Thurstonian models. It introduces the important
      concept of stimulus variability and the fundamental measure of sensory
      difference: d'. It indicates how the paradox of discriminatory non
      discriminators, which had puzzled researchers for years, can be simply explained
      using the model. It considers how memory effects and the complex interactions in
      the mouth can reduce d' by increasing the variance of sensory distributions.

PMID- 20677447
TI  - [Detention--law or colours of law?].

PMID- 20677449
TI  - [Role of prebiotic oligosaccharides in prevention of gastrointestinal infections:
      a review].
AB  - Gastrointestinal disorders are still a main world public health problem.
      Scientific progress shows that and inadequate balance in intestinal microbiota
      (IM) plays a crucial role in its pathogenesis. Evidence indicates that one way to
      modulate the IM is through the use of prebiotics. These oligosaccharides
      stimulate the growth of benefic bacteria and increase the resistance to invading
      pathogens. Research using animals show that the consumption of prebiotics could
      be implicated in prevention and treatment of diarrhea. Studies in healthy infants
      also indicate that the consumption of prebiotic mixtures
      (galactooligosaccharides/fructooligosaccharides, inulin/galactooligosaccharides)
      decreases the incidence of fever, infections and pathogens. These results
      represent a great potential for functional foods that contain prebiotics, mainly
      the infant formulas. However, results of other clinical studies for prebiotics
      effects on diarrhea are not conclusive. Specially those studies that include
      patients with an altered IM (like the elderly), patients with chronic intestinal
      inflammation and with diarrhea associated to antibiotic treatments. There is a
      need for more biochemical and microbiological studies in humans at different ages
      and intestinal health conditions, in order to determine when prebiotics may
      effectively function on infections.

PMID- 20677450
TI  - [Birth weight and later nutritional status, cognitive development and job status:
      a critical revision].
AB  - The impact of prenatal nutritional status, assessed through birth weight (BW) and
      their effects in the short, medium and long-term on nutritional status, cognitive
      development and job status in the adult life, has been a problem of interest for
      several researchers; as regards, some of these report a positive and significant
      association between these variables and others do not find any relation. Children
      with insufficient, low or very low BW despite the early more deteriorate
      nutritional status should present higher risk for brain maturation, failure
      cognitive development and lowered head circumference which implies both lowered
      brain volume and intellectual development. In the short and medium-term, this
      situation damages the learning process at school-age, while in the long-term this
      might condition the quality of jobs. At present, the body of knowledge pinpoints
      that findings related to these associations is not conclusive verifying a great
      controversy in these matters. This review article has the purpose of analyzing
      the current evidence, in order to stimulate research about to these aspects which
      are relevant for child development and their future life.

PMID- 20677452
TI  - [Active Substance Index (AKS) percentile distribution in pediatric ages].
AB  - The aim of this study was to discern the percentile distribution of the Active
      Substance Index (AKS) in boys and girls aged 4 to 9 years in order to obtain
      reference values for this indicator. This index was calculated in 3634 healthy
      and well-nourished children with normal stature from a poor urban community at
      Centro de Atencion Nutricional Infantil Antimano (CANIA), within the period
      between January 1999 and December 2007. Children with prematurity backgrounds,
      pubertal growth spurts, or with chronic pathologies, whether defined or under
      study, were excluded. The Dugdale & Griffiths two-skinfold equation for boys and
      girls shorter than 150 cm and 140 cm, respectively was used to obtain the fat
      body mass required to estimate the AKS index. The variables were measured by
      standardized anthropometrics technicians, with quality control every 4 months as
      recommended by international standards. Descriptive statistics of the AKS index
      and variables used for their calculation were obtained, as well as index
      percentiles 3, 10, 25, 50, 75, 90, and 97. Tests applied included Kolmogorov
      Smirnoff, Anova one-way, Chi Square, Tukey and bivariated correlations (p <
      0.05). The AKS index behavior exhibited higher values in the boys, decreasing
      with age in both sexes, ranging from 1.28 to 1.04 in the boys and from 1.17 to
      0.94 in the girls. Statistically significant differences were found for each age
      and sex. These results provide the AKS index percentile distribution values
      needed for nutritional assessments in pediatric ages. These values should be
      validated and their effectiveness should be studied.

PMID- 20677451
TI  - [An approach to a sanitary and social problem: urinary iodine excretion in
      pregnant women from a iodine deficient region].
AB  - The urinary iodine excretion (UIE) assay is an effective method to detect reduced
      iodine intake. UIE was measured in two different samples (morning and evening)
      from 121 pregnant women, with a turbid-metric method modified by Pino (normal
      value =150 ugl/1). Furthermore, thyroid function was evaluated in pregnant women
      with UIE <100 ug/l. From 121 pregnant women, the UIE was normal in 75 with
      similar morning and evening samples (morning: 305.2 +/- 7.0; evening: 319.2 +/-
      8.8; p: NS). The UIE did no showed differences in different trimesters and in
      morning and evening samples. The UIE was low in 46 women (36.9%), without
      significant differences between morning and evening (morning: 88.12 +/- 5.07
      microg/l; evening: 88.7 +/- 6.2 microg/l; p: NS). Normal or low UIE were not
      influenced by the age of pregnant women and 45% of pregnant women with UIE < 100
      ug/l showed impaired thyroid function. Morning and evening study of UIE allowed
      us to detect a higher number of pregnant women with low iodine intake. This study
      let us to find thyroid function abnormalities likes a screening method, because
      in our state there is not a public screening program for gestational
      hypothyroidism.

PMID- 20677453
TI  - [Nutritional risk in no-institutionalized older, determined for the mini
      nutritional assessment (MNA)].
AB  - The objective of this study was to determine the prevalence of the risk of
      undernutrition by evaluating the nutritional status in a representative sample of
      older people in Ourense. The total sample was 728 subjects (63.6% woman and 36.4%
      men) with a mean age of 80.7 +/- 7.4 years old. Anthropometric parameters
      (weight, distance heel-knee, calf circumference and mid-arm circumference) were
      determined and the MNA (Mini Nutritional Assessment) was applied and 70% of
      individuals with nutritional problems were identified (57.5% with nutritional
      risk and 12.5% malnourished). The subjects aged between 65 and 70 years old, 81
      and over, and females presented higher nutritional problems. The items that were
      observed most frequently in the studied population and therefore responsible for
      this nutritional situation were the involuntary loss of weight, consumption of at
      least one serving of protein per day, low daily liquid intakes, loss of appetite,
      taking more than 3 prescription drugs per day and to have a limited mobility.

PMID- 20677455
TI  - [Toxigenic Bacillus cereus detection in lactic products with spices and
      dehydrated milk collected in Costa Rica].
AB  - Bacillus cereus is a Gram positive rod widely distributed in nature and
      associated to different types of food that, under some circumstances, may cause
      pathology to human beings. Diarrheic and emetic strains have been described based
      on the type of toxins produced. In order to determine the risk to health
      represented by this bacteria, the toxigenic potential of strains isolated from
      cheese with spices, spread cheese with spices and dehydrated milk, all sold in
      San Jose, Costa Rica, were determined using a multiplex PCR technique with
      oligonucleotides specific for the genes coding toxins HBL and Nhe. From 45
      samples collected, 15 isolates of B cereus were obtained (60% coming from spread
      cheese with spices 7% from dehydrated milk and 13% from cheese with spices). All
      the strains analyzed presented at least one of the genes analyzed; six of them,
      coming from dehydrated milk and spread cheese, showed molecular evidence of the
      genes nheB, nheA, nheC, hblD, hblA y hblC, confirming the correlation described
      for the presence of operons codifying for HBL and Nhe. Nevertheless, the no
      detection of a gene cannot be considered as a definitive proof of its absence,
      given the existence of polymorphism in the sequences of the genes analyzed. The
      results obtained show that multiple of the B cereus strains found in lactic
      products from Costa Rica have the necessary genes for synthesizing toxins, so the
      correct handling of these products is very important since they can represent a
      risk for public health.

PMID- 20677454
TI  - [Retinolemia, vitamin A intake, and blood pressure in the elderly].
AB  - The objective of this study was to evaluate the retinolemia and consumption of
      vitamin A rich foods and their association with blood pressure levels in the
      elderly. This is a cross-sectional study, with a systematic sample of 297 elderly
      subjects enrolled at the Family Health Program of Camaragibe, Pernambuco, between
      November/December of 2003. Vitamin A status was assessed by retinolemia (HPLC)
      and by the consumption of vitamin A rich foods (food frequency questionnaire).
      Blood pressure levels were classified according to the V Brazilian Guidelines on
      Hypertension. A prevalence of inadequate retinolemia (< 1.05 micromol/L) of 26.3%
      (CI95% 21.4-31.9) was found. The frequency of preformed vitamin A intake (>
      3x/week) was lower (p = 0.000) than the provitamin A intake. The prevalence of
      systemic arterial hypertension (SAH) was 58.6% (CI95% 52.7-64.3). Isolated
      systolic hypertension was more prevalent among subjects. There was no correlation
      between retinolemia and vitamin A rich-food intake (p > 0.05). In addition, there
      was no association between blood pressure levels and vitamin A rich-food intake
      (p > 0.05). However, retinolemia in the elderly classified in stage 1 of SAH was
      higher (p = 0.02) than in the elderly with great/normal blood pressure. The
      findings suggest a vulnerability of these subjects to hypovitaminosis A and SAH.
      Nevertheless, the role of vitamin A in the endothelial function modulation and
      inflammatory responses associated to SAH should be addressed in future studies.

PMID- 20677456
TI  - [Differences in food consumption associated with ethnic group and acculturation
      in the Metropolitan Region of Santiago, Chile].
AB  - In order to identify differences in the food consumption and expenditure habits
      of Mapuches according to their ethnic group as consumers as well as their degree
      of acculturation, a personal survey was conducted on 400 people stratified by
      ethnic group in four districts of the Metropolitan Region of Santiago, Chile. The
      empirical results showed that habits regarding the consumption of food groups
      included in the Family Budget Survey did not present any significant differences
      depending on the consumer's ethnic group, although the monthly expenditure on
      food is lower in Mapuche households. The ethnic origin and degree of
      acculturation in Mapuches are only significantly associated with the consumption
      of mate (herbal infusion) and food in restaurants. Mapuches maintain both food
      practices belonging to their traditional culture as well as foods incorporated
      more recently, such as mate. The degree of acculturation is significantly
      associated with the consumption of these foods; bi-cultural Mapuches present a
      higher probability of consuming a greater range of traditional foods than
      accultured Mapuches.

PMID- 20677457
TI  - [Effect of processing on the antioxidant activity of amaranth grain].
AB  - Amaranth has attracted increasing interest over recent decades because of its
      nutritional, functional and agricultural characteristics. Amaranth grain can be
      cooked, popped, toasted, extruded or milled for consumption. This study
      investigated the effect of these processes on the antioxidant activity of
      amaranth grain. Total phenolic content and in vitro antioxidant activity were
      determined according to two methods: inhibition of lipid oxidation using the beta
      carotene/linoleic acid system and the antioxidant activity index using the
      Rancimat apparatus. The processing reduced the mean total phenolics content in
      amaranth grain from 31.7 to 22.0 mg of gallic acid equivalent/g of dry residue.
      It was observed that the ethanol extract from toasted grain was the only one that
      presented a lower antioxidant activity index compared with the raw grain (1.3
      versus 1.7). The extrusion, toasting and popping processes did not change the
      capacity to inhibit amaranth lipid oxidation (55%). However, cooking increased
      the inhibition of lipid oxidation (79%), perhaps because of the longer time at
      high temperatures in this process (100 degrees C/10 min). The most common methods
      for processing amaranth grain caused reductions in the total phenolics content,
      although the antioxidant activity of popped and extruded grain, evaluated by the
      two methods, was similar to that of the raw grain. Both raw and processed
      amaranth grain presents antioxidant potential. Polyphenols, anthocyanins,
      flavonoids, tocopherols, vitamin C levels and Maillard reaction products may be
      related to the antioxidant activity of this grain.

PMID- 20677458
TI  - [Effect of calcium hydroxide concentration and cooking time of corn grain (Zea
      mays L.) nixtamalized, over physicochemical and rheological nixtamal
      characteristics].
AB  - The effect of calcium hydroxide (Ca(OH)2) concentration and cooking time on
      physicochemical and pasting properties of maize, during traditional
      nixtamalization was evaluated. It was observed that the higher the Ca(OH)2
      concentration and cooking time the higher the gelatinization temperature. Grain
      samples treated with 2 g/100 g of Ca(OH)2 and 60 min of cooking time presented
      higher calcium absorption (0.152 g/100 g) showing a significant increment
      (approximately 500 g/100 g). Results of X-ray diffraction showed that all the
      samples had X-ray diffraction pattern of starch type A, showing differences in
      the intensity of the diffraction as indicated by the percentage of cristallinity.
      The apparent viscosity of the nixtamal considerably decreased when the processes
      conditions were higher. Water retention capacity increased with temperature.

PMID- 20677459
TI  - [Gluten-free cookies prepared with sorghum flour].
AB  - Considering that sorghum is a gluten free flour, it could be proposed as an
      ingredient to produce alternative bakery products for the subjects with Celiac
      Disease, since they do not have many food options available in the market. For
      this reason, the main goal of this study is to develop chocolate cookies with
      sorghum flour (Sorghum vulgare). The experimental design used was the simplex
      lattice factor to compare the following variables: sorghum flour (50-100%), rice
      flour (0-50%) and corn starch (0-50%), totaling up to ten experiments. The
      formulations IX and X were selected as the ones with the highest sensorial scores
      The sorghum flour, regular chocolate cookies and gluten free cookies were
      submitted to physicochemical analysis. Physical and sensorial analysis using
      Quantitative Descriptive Analysis (QDA) and hedonic analysis were performed for
      the two cookies preparation. Sorghum flour presented characteristics compared
      with the described by the food regulation laws. The preparations that presented
      satisfactory sensorial characteristics were the ones that had 58 and 67% of
      sorghum flour, 8 and 17% of rice flour, 33 and 17% of corn starch, respectively.
      The performance for both IX and X formulations was 0,92 and the specific volume
      was 1,54 and 1.46 cm3/g, respectively. When compared with regular cookies, the
      differences on most of the sensorial attributes evaluated on sorghum cookies were
      not statistically significant (P < 0.05), except for the color and the odour. All
      the sensorial scores reached values equal or higher than 7 for both samples and
      most of them scored 8. The results showed the feasibility of including sorghum
      flour on the manufacture of gluten free cookies.

PMID- 20677461
TI  - HIT standardization--too much, too soon?

PMID- 20677460
TI  - [Development of mixed drink of coconut water, pineapple and acerola pulp].
AB  - The purpose of the present work was to develop a blended beverage based on green
      coconut (Cocos nucifera L.) water, pineapple (Ananas comosus) and acerola
      (Malpighia emarginata D. C.) pulps as a ready to drink product, combining the
      sensory acceptance, nutritional and functional compounds of these fruits. Ten
      formulations of mixed beverages were evaluated with regard physicochemical
      determinations, functional compounds and sensorial attributes. Since here was no
      significative change in the acceptance of here formulations, the product composed
      of 65% green coconut water, 15% of pineapple and 20% acerola pulp was selected
      based on the best combination of nutritional components. This formulation
      presented the required characteristics for a new commercial product.

PMID- 20677462
TI  - Performance standards vs. standardized performance. A choice for optimizing
      quality of care.

PMID- 20677463
TI  - Protection detail. Protecting against breach of electronic protected health
      information.
AB  - Covered entities need to conduct risk assessments that cover the requirements of
      HIPAA, HITECH and Meaningful use, and create a process for steady and consistent
      mitigation of known gaps and vulnerabilities based on risk. Reducing risk of
      vulnerabilities of unauthorized access to your ePHI can be done via safeguards
      and controls, plus audits and monitoring. When reducing risk is outside of a
      covered entities control, audits and monitoring are required in order to
      demonstrate due diligence. Know where your ePHI is stored, where it is at risk,
      and take steps now to reduce or eliminate the risk. Encrypt vulnerable locations.
      Encrypt sensitive data. By doing so, you will be protecting your organization by
      reducing risk of breach of ePHI. Finally, don't forget what is sometimes
      considered to be the hardest part--documenting your compliance activities in
      order to demonstrate evidence of due diligence in and avoid major $$$$ penalties
      for negligence under the HITECH Act of 2009.

PMID- 20677464
TI  - There's an app for that--mHealth takes center stage.

PMID- 20677465
TI  - Connecting for care--nursing and health information exchange.

PMID- 20677466
TI  - Closing the loop--integrating an enterprise-wide pharmacy system.

PMID- 20677467
TI  - IT systems and third-party products. Do you know who manufactures the components
      of your system?

PMID- 20677468
TI  - Continuous healing relationships through connectivity. As the nation edges to
      widespread implementation of EMRs, physicians are concerned about weakening the
      important doctor-patient relationship.

PMID- 20677469
TI  - Barriers to cross--institutional health information exchange: a literature
      review.
AB  - While the development of health information technology, particularly electronic
      health records (EHR), is a triumph for the advancement of healthcare, non
      interoperable clinical data systems lead to fragmented communication and
      incomplete records. If interoperable HIT systems could be achieved integrated HIT
      could be leveraged to lessen medical errors, improve patient care and optimize
      epidemiological research. To understand the barriers to interoperability or
      health information exchange (HIE), we reviewed the literature on HIT and barriers
      to HIE. Our search yielded 492 articles, 25 meeting our inclusion criteria. In
      general, we found that the predominant barriers to HIE are need for standards,
      security concerns, economic loss to competitors, and federated systems. Research
      on interoperability is limited because most HIE programs are still in formative
      stages. More research is needed to fully understand interoperability of HIT, how
      to overcome the barriers to interoperability, and how to design HIT to better
      facilitate HIE.

PMID- 20677470
TI  - Medical device data systems and FDA regulation. Should medical device data
      systems require FDA clearance?
AB  - It is widely understood why medical devices need to be regulated by the FDA and
      other governing bodies. However medical software does not typically require the
      same level of regulation. Currently the FDA is investigating whether one type of
      medical software, Medical Device Data Systems (MDDS), should require FDA
      clearance because of the potential risk they impose when interconnected with
      medical devices. Hospitals are looking to implement MDDS because the technology
      allows nursing staff to spend more time on direct patient care and reduces
      charting errors. This article will explore the FDA's proposal and will review the
      possible risks and provide a rationale for why MDDS should be regulated by the
      FDA and why MDDS vendors should have the right level of quality and risk
      management procedures in place to ensure that they are developing and bringing to
      market the safest products possible.

PMID- 20677471
TI  - QRDA--technology overview and lessons learned.
AB  - Quality of healthcare is a high priority for several years but there was no
      standard until recently. The standards body, HL7 released draft standard for
      Quality Reporting Document Architecture (QRDA) with an aim to develop an
      electronic data standard for healthcare information systems to use in
      communicating patient level quality measurement data across disparate systems.
      This standard would enable Healthcare providers those use Electronic Health
      Record (EHR) systems to generate Quality Reporting documents to be consumed by
      payer agencies such as Centers Medicare and Medicaid Services (CMS) replacing
      proprietary file formats that existed in this space previously, This paper
      discusses various features of this new standard, which promotes interoperability
      and easy adoption, the three categories proposed by the QRDA standard and their
      application in different contexts, measure sets and measures and finally the
      relationship of this QRDA standard to the HQMF (eMeasure) standard proposed by
      National Quality Forum (NQF) in collaboration with HL7 to standardize the Quality
      Measures across the healthcare landscape. This paper also provides high-lights on
      early adoption of QRDA standard by Centers Medicare and Medicaid Services (CMS)
      for their Physician Quality Reporting Initiative (PQRI) program.

PMID- 20677472
TI  - Certification of primary care electronic medical records: lessons learned from
      Canada.
AB  - Understanding international approaches to certification of electronic medical
      records (EMRs) in an effort to achieve widespread meaningful use is particularly
      timely. Canada's 34,000 primary care doctors cover a population of 33 million in
      13 jurisdictions. A recent survey suggested only 14 percent of Canadian doctors
      are utilizing EMRs in a clinically meaningful way. In order to accelerate EMR
      adoption, most jurisdictions have initiated EMR programs. The objectives of these
      programs are to 1.) certify EMRs to ensure they meet needs for high quality care
      delivery; 2.) provide funding for EMR acquisition, implementation and support;
      3.) supply services to assist with EMR purchase and implementation; and 4.)
      measure adoption and impact of EMR use. In this article we review the impact of
      certification on the advancement of EMR use in Canada and discuss both the
      benefits that these programs have provided and the challenges that they have
      posed.

PMID- 20677473
TI  - The conversion to electronic hospital notes at Mayo Clinic. Overcoming barriers
      and challenges.
AB  - This article describes the conversion to electronic hospital notes at a large,
      multi-specialty group practice: Mayo Clinic in Rochester, Minnesota. Because of
      the size of the institution and the barriers to the adoption of electronic notes,
      the process was a gradual one that took several years. Making a convincing case
      for change to institutional leaders and maintaining their support was crucial to
      success. Equally vital was the careful investigation of user requirements and the
      development of software features that allowed providers to complete their notes
      quickly in the fast-paced hospital environment. Care providers discovered the
      value of having immediate access to legible hospital notes throughout the campus
      and from remote locations.

PMID- 20677474
TI  - How to select end user clinical data entry devices. Rush University Medical
      Center develops tool to identify the quantity of devices needed for the
      implementation of a new EMR and CPOE system.
AB  - Selecting the right types and quantities of computers to support data entry to an
      inpatient Electronic Medical Record (EMR) can be challenging. In addition to
      software and hardware considerations, many other variables affect the decision
      including staffing levels, hospital workflows, and floor plans. Rush University
      Medical Center (RUMC) developed a tool to help identify the quantity of devices
      needed in a Patient Care Unit (PCU). RUMC successfully used the tool in selecting
      the quantity of devices needed for the implementation of a new EMR and
      Computerized Provider Order Entry (CPOE) system. This case study describes the
      use of the tool to determine quantities of PCU devices, the advantages and
      disadvantages of different types of computing devices for bedside documentation
      and areas that require special considerations in the selection of devices.

PMID- 20677475
TI  - Workflow viewpoints: Analysis of nursing workflow documentation in the electronic
      health record.
AB  - This article amplifies the emphasis on organizational workflow reignited by the
      Institute of Medicine reports on healthcare quality. The analysis of nursing
      workflow is central to understanding the power of technology to modify the
      fundamental constructs of nursing practice. The aim is to understand the
      evolution of nursing workflow and the concept of workflow from the management and
      computer science perspectives used in electronic health records and computerized
      provider order entry. The understanding of the workflow models within health
      information disciplines may improve the model of nursing workflow underlying the
      implementation of electronic health record systems. The article follows the
      Walker and Avant evolutionary method of concept analysis.

PMID- 20677476
TI  - Approach to obesity in patients with pelvic floor dysfunction.

PMID- 20677477
TI  - Prevalence of urinary symptoms in morbidly obese women and changes after
      bariatric surgery.
AB  - OBJECTIVE: To evaluate the impact of rapid weight loss following bariatric
      surgery on urinary symptom frequency and overall quality of life. STUDY DESIGN:
      Validated questionnaires (Urinary Distress Inventory [UDI-6] and Incontinence
      Impact Questionnaire [IIQ-7]), were mailed to all women who underwent bariatric
      surgery at Temple University Hospital between January 2004 and March 2006.
      McNemar test of paired proportions was used for analysis. RESULTS: Mean body mass
      index prior to surgery was 47.5 and after surgery was 31.0, with an average
      weight loss of 49.2 kg. About half the subjects had stress incontinence, 32% had
      frequency and 24.8% had urgency at baseline. Twenty-six percent of the subjects
      were frustrated and emotionally distressed by the urinary symptoms at baseline,
      while one fifth reported interference with performing household chores, travel
      and other activities. There was a significant improvement in stress incontinence
      (p < 0.001), frequency and leakage of any degree and overall quality of life
      subsequent to surgery. CONCLUSION: Body mass index has a significant effect on
      urinary symptoms as an independent factor. We report a marked improvement in
      stress incontinence symptom frequency and symptom bother with rapid weight loss
      subsequent to bariatric surgery in morbidly obese women.

PMID- 20677479
TI  - Why the twinning rate is higher in Africa than elsewhere: an analysis of selected
      factors.
AB  - OBJECTIVE: To examine the rate of spontaneous twinning in selected countries in
      order to evaluate the impact of environmental stress and related socioeconomic
      factors on balancing reproductive activity and longevity. STUDY DESIGN: Four
      countries with similar ancestry were considered, 2 in Africa and 2 in the
      Caribbean. Data on gross domestic product per capita, as a measure of indigenous
      conditions, access to proper diet, health care, sanitation and shelter were
      compared with the relative rate of twinning. RESULTS: The data show an inverse
      relationship between wealth and environmental conditions, and the incidence of
      multiple gestations. CONCLUSION: Through goods and services, improved living
      conditions reduce environmental stress and its adverse effect on the balance of
      biologic reproduction vs. longevity. In addition, breast-feeding, as a social
      expression and an economic easement, correlates with the chance of conceiving
      twins in a subsequent pregnancy. It would thus appear that the twinning rate can
      be taken as a barometer of the population's biologic attempt to perpetuate its
      gene pool expeditiously when an existential threat occurs.

PMID- 20677478
TI  - Medical students' awareness of traditional Southwest Native American values
      during pregnancy: a randomized, controlled trial.
AB  - OBJECTIVE: To determine if medical students' attendance at specialized prenatal
      clinics for Southwest Native American women would impact their awareness of and
      comfort in discussing traditional and unique values during pregnancy. STUDY
      DESIGN: In this unblinded, randomized trial, all 154 third-year students rotating
      consecutively on our obstetrics-gynecology clerkship consented to enrolling in
      this study. Participants were randomly assigned either to attend a high-risk
      prenatal clinic (rural or urban locations) for Native American women or to not
      attend (control group). Each anonymously answered a 20-question survey at the
      beginning and end of the clerkship about their comfort level and their awareness
      of patients' beliefs. A mixed model ANOVA was used to compare differences in
      scores between the groups while accounting for cluster effects in the study
      design. RESULTS: Regardless of whether the clinic was rural or urban, students
      became much more comfortable than controls in talking with Native American women
      about their pregnancy (p < 0.005). This applied especially to discussions about
      patients' spiritual beliefs, taboos that may affect pregnancy, participation in
      tribal ceremonies and belief in traditional medicine. As compared with the
      control group, students assigned to either clinic became more aware of how
      spirituality played an integral role in pregnancy (p < 0.05). CONCLUSION:
      Attendance at these specialized prenatal clinics enhanced medical students'
      comfort in talking with pregnant Native American women about the integrative
      roles of spiritual beliefs, tribal ceremonies and complementary medicine in their
      pregnancy outcome.

PMID- 20677481
TI  - Risk factors for complete molar pregnancy: a study in Iran.
AB  - OBJECTIVE: To evaluate some of the risk factors of complete molar pregnancy.
      STUDY DESIGN: A case-control study was performed on 91 cases of complete molar
      pregnancy (case group) and 295 cases of normal, term pregnancy with a live
      neonate (control group). Then the maternal age, parity and gravidity, blood group
      and Rh, history of molar pregnancy, consanguinity, history of spontaneous
      abortion, contraception method and nationality (Afghan or Iranian) were compared
      in the 2 groups. RESULTS: History of molar pregnancy (OR [odds ratio], 95% CI 5.7
      [1.2-25.61), spontaneous abortion (OR, 95% CI 2.1 [1.7-2.61), maternal age > 35
      years old (OR, 95% CI 2.3 [1.3-3.9]) and < 20 years old (OR, 95% CI 1.6 [1.4
      1.9]), consanguinity (OR, 95% CI 1.3 [1.1-1.51) and Iranian nationality (OR, 95%
      CI 1.9 [(1.5-2.4]) were found to be risk factors for molar pregnancy. CONCLUSION:
      History of molar pregnancy and spontaneous abortion, maternal age > 35 and < 20,
      consanguinity and nationality may be risk factors for molar pregnancy.

PMID- 20677480
TI  - Endometrial ablation with paracervical block.
AB  - OBJECTIVE: To evaluate the safety, feasibility and efficacy of endometrial
      ablation under local anesthesia. STUDY DESIGN: A prospective cohort study was
      performed at the gynecology department of a large teaching hospital. Women with
      dysfunctional uterine bleeding were included to undergo NovaSure endometrial
      ablation with paracervical block. We measured the acceptability, pain score
      (visual analog score scale), amenorrhea, and patients' satisfaction after the
      procedure. RESULTS: We treated 33 patients. No complications occurred during the
      procedure or postoperatively. Of the 33 women, 28 found treatment with NovaSure
      endometrial ablation under local anesthetics acceptable. After 24 hours, 23 of 33
      women reported to be pain free, whereas 10 women still had mild pain. Twenty
      women developed amenorrhea (60.6%) and 13 women hypomenorrhea (39.4%). All women
      were satisfied with the treatment result and would recommend it to a friend.
      CONCLUSION: NovaSure endometrial ablation performed under local anesthesia is a
      safe, feasible and efficacious procedure.

PMID- 20677482
TI  - Tumor necrosis factor-alpha-induced cyclooxygenase-2 overexpression in eutopic
      endometrium of women with endometriosis by stromal cell culture through nuclear
      factor-kappaB activation.
AB  - OBJECTIVE: To investigate the role of NF-kappaB during the induction of COX-2 by
      TNF-alpha in the eutopic endometrium of women with and without endometriosis
      using stromal cell culture. STUDY DESIGN: Experimental study in cultured stromal
      cells of the eutopic endometrium of women with and without endometriosis in the
      presence of TNF-alpha. RESULTS: Within 5-20 minutes of stimulation with TNF
      alpha, p-IkappaB was clearly observed in the eutopic endometrium of women with
      endometriosis and in that of women without endometriosis. COX-2 protein was
      significantly induced by treatment with TNF-alpha in both eutopic endometrial
      stromal cells of women with and without endometriosis (p < 0.05), but the degree
      of induction was significantly increased in eutopic endometrial stromal cells of
      women with endometriosis than those of women without endometriosis (p < 0.05).
      CONCLUSION: Overexpression of COX-2 by TNF-alpha in the eutopic endometrium of
      women with endometriosis may play a critical role in such pathophysiologic
      processes as endometriosis formation.

PMID- 20677483
TI  - Comparison of 2 commercially available human chorionic gonadotropin immunoassays
      used in the management of gestational trophoblastic neoplasia.
AB  - OBJECTIVE: To compare serum human chorionic gonadotropin (hCG) titers using 2
      commercially available hCG immunoassays in patients with gestational
      trophoblastic neoplasia (GTN). STUDY DESIGN: A total of 213 serum samples from 39
      patients with uneventful moles and 697 serum samples from 17 patients with low
      risk and high-risk GTN were obtained and subsequently measured with both the hCG
      C-terminal (hCG-CTP) and DPC Immulite 2000 tests. RESULTS: In patients with
      uneventful moles and GTN, serum hCG levels recorded using the hCG-CTP and DPC
      Immulite 2000 tests correlated well (r2 = 0.936 and r2 = 0.958). However, the
      serum hCG titers measured using the DPC Immulite 2000 assay were approximately
      2.5- and 2.7-fold higher than those measured with the hCG-CTP test (p < 0.0001)
      when lower titers of hCG (< 40 mIU/mL) were tested. In addition, 3 and 1 patient,
      respectivelyl, with uneventful mole and GTN obtained positive results with the
      DPC Immulite 2000 test (3.0-4.2 mIU/mL) after demonstrating undetectable hCG
      levels with the hCG-CTP test (< 1.0 mIU/mL). CONCLUSION: At the lower levels of
      hCG, a few discrepancies between hCG titers measured using the 2 commercial
      immunoassays arose and may be attributed to the existence of hCG-related
      molecules. However, these hCG metabolites disappeared rapidly, the clinical
      importance of which remains unclear.

PMID- 20677484
TI  - Conservative surgical management of placenta accreta: a report of 3 cases.
AB  - BACKGROUND: Placenta accreta is often diagnosed at the time of delivery and is a
      cause of postpartum hemorrhage, morbidity and mortality. The standard treatment
      for placenta accreta is hysterectomy to avoid acute blood loss and shock. A
      conservative surgical approach to the treatment of placenta accreta will allow
      immediate cure while preserving the patient's future fertility. CASES: A 39-year
      old woman with placenta accreta diagnosed at the time of vaginal delivery was
      successfully treated with resection of the placental implantation site. A 33-year
      old woman and a 35-year-old woman with placenta accreta/increta diagnosed at the
      time of cesarean section were successfully treated with resection of the
      placental implantation site. One patient has since conceived and given birth.
      CONCLUSION: Placenta accreta and placenta increta can be safely and successfully
      treated, in some well-selected cases, by resection of the placental implantation
      site and uterine repair. This conservative surgical management provides immediate
      therapy, reduces blood loss and preserves fertility.

PMID- 20677485
TI  - Breast mass in a patient with ovarian cancer: a case report.
AB  - BACKGROUND: Less than 1% of malignant breast masses represent metastases from an
      extramammary source. Gynecologic tumors rarely metastasize to the breast. We
      report 2 patients who developed a breast mass following a known diagnosis of
      metastatic ovarian carcinoma or primary peritoneal carcinoma. CASE REPORTS: A 28
      year-old woman receiving therapy for recurrent ovarian cancer developed a breast
      mass with pleomorphic calcifications that was an ovarian cancer metastasis. A 61
      year-old woman with primary peritoneal carcinomatosis developed a new primary
      breast tumor expressing CA 125 at the end of adjuvant therapy for peritoneal
      cancer. CONCLUSION: Treatment and prognosis for metastatic and primary breast
      lesions are different, therefore accurate differentiation using radiographic and
      pathologic criteria is essential. We describe unique features of primary and
      metastatic breast lesions in patients with ovarian cancer.

PMID- 20677486
TI  - Ischiorectal abscess and ischiorectal-vaginal fistula as delayed complications of
      posterior intravaginal slingplasty: a case report.
AB  - BACKGROUND: Synthetic meshes have been used extensively to augment surgical
      management of pelvic organ prolapses. Posterior intravaginal sling (IVS) is a
      technique used for correcting vaginal vault/apical prolapse, posterior vaginal
      prolapse or rectocele. There are limited data on long-term safety of this
      procedure. In a subanalysis of the IVS tapes from the SUSPEND trial performed
      secondary to the large number of patients with complications of suburethral sling
      erosions after IVS, it was noted that the sling erosion tended to have a delayed
      presentation secondary to poor incorporation of the mesh. CASE: A 48-year-old
      woman with cystocele, uterine prolapse and rectocele had undergone total vaginal
      hysterectomy, mesh-augmented anterior repair, posterior colporrhaphy and
      posterior intravaginal slingplasty (IVS) in July 2005. Thirty months after the
      surgery, she presented with gradual symptoms of copious vaginal discharge for
      several weeks followed by constant right buttock pain and swelling. Examination
      was notable for intact mesh with no signs of erosion and a 3-cm induration deep
      within the right buttock. Computed tomography suggested a pelvic abscess.
      Magnetic resonance imaging confirmed a right ischiorectal fossa abscess and a
      vaginal fistula. The patient underwent sling excision, right ischiorectal fossa
      exploration and vaginal fistula repair. A fistulous tract was found to extend
      along the intact sling from the vaginal epithelium toward the right ischiorectal
      fossa. At 2 months' followup, there were no recurrences or other complications.
      CONCLUSION: This is the first report of a delayed complication of an ischiorectal
      abscess associated with an ischiorectal-vaginal fistula that presented 30 months
      after the placement of a posterior IVS.

PMID- 20677487
TI  - Ovarian ectopic pregnancy 6 years after supracervical cesarean hysterectomy: a
      case report.
AB  - BACKGROUND: Pregnancy after hysterectomy is very rare, with fewer than 40 cases
      reported in the English-language literature. The majority of cases are diagnosed
      in the early posthysterectomy, postoperative period, indicating that the
      pregnancy was present at the time of hysterectomy. Cases diagnosed remotely from
      the time of hysterectomy result from a fistulous tract allowing sperm access to
      the peritoneal cavity. CASE: A 37-year-old woman 6 years since a supracervical
      cesarean hysterectomy was treated for a ruptured ovarian pregnancy. CONCLUSION: A
      woman with intact ovaries presenting with abdominal pain, despite a prior
      hysterectomy, should be considered at risk for ectopic pregnancy. The presence of
      a cervix may increase that risk.

PMID- 20677488
TI  - Ruptured tuboovarian abscess and septic shock with Clostridium perfringens in a
      postmenopausal woman: a case report.
AB  - BACKGROUND: Clostridium perfringens is the most common causative organism of gas
      gangrene, a necrotizing infection of soft tissue classically associated with
      traumatic injuries. Recently, awareness of its occurrence in spontaneous
      nontraumatic contexts has been increasing. The authors report an unusual case of
      nontraumatic/spontaneous C perfringens gas gangrene localized to the adnexae.
      CASE: A 55-year-old woman presented with abdominal complaints and had surgery
      because the computed tomographic finding of air in the abdomen led to a
      preoperative diagnosis of perforated bowel. An infected, draining, right
      tuboovarian complex and infected left tube were removed. The patient had a stormy
      postoperative course and was ultimately diagnosed with C perfringens
      infection/sepsis; she had to be readmitted over a month after discharge for
      drainage of a pelvic abscess, also due to clostridial infection. The patient
      ultimately underwent hysterectomy with removal of remaining adnexa. The
      hysterectomy specimen revealed endometrial carcinoma. CONCLUSION: C perfringens
      can cause adnexal infection in the absence of trauma. Diagnosis may be difficult.
      Timely, aggressive surgical and medical therapy is imperative. When such cases
      occur, malignancy should be suspected.

PMID- 20677489
TI  - Laparoscopic gonadectomy in a kidney transplant patient with pure gonadal
      dysgenesis: a case report.
AB  - BACKGROUND: Laparoscopy has been successfully used following renal
      transplantation for many procedures, including native kidney nephrectomy,
      revision of transplant ureters and cholecystectomy. Laparoscopic surgery has also
      been used recently to treat pelvic disorders in patients after renal
      transplantation, such as removal of endometriotic cyst and hysterectomy. In such
      cases, we must pay special attention to the anatomy of the renal graft
      transplanted into the pelvic cavity. CASE: A woman received a kidney transplant
      at 7 years old, with her mother as the donor. At 19 years old, she was diagnosed
      with pure gonadal dysgenesis and began hormone replacement therapy and monitoring
      of tumor markers. At 23 years old, laparoscopic gonadectomy was performed under
      general anesthesia. Bilateral atrophic gonads were removed without any
      complications. The renal graft in the right hemipelvis did not obstruct the
      operation. CONCLUSION: To our knowledge, this case is the first published report
      of laparoscopic castration in a patient with a sexual differentiation disorder
      and prior renal transplantation.

PMID- 20677490
TI  - [The recipe of "good aging" reserves some surprises].

PMID- 20677491
TI  - [The transfers from Ehpad hospital, numerous but justified].

PMID- 20677492
TI  - [Seminar "the case of the aged, for aging otherwise...and better"].

PMID- 20677493
TI  - [Autonomy at home: 18 measurements of the the project "Live alone"].

PMID- 20677494
TI  - [The advantage of multidisciplinary treatment of presbycusis].
AB  - Attributable to the ageing of the hearing system, presbycusis presents a wide
      variability in the general population. Early detection is necessary in order to
      be able to provide the patient with a suitable hearing aid. Collaboration between
      otolaryngologists and geriatricians proves to be advantageous as a consultation
      for a memory complaint may be the opportunity to detect presbycusis and vice
      versa.

PMID- 20677495
TI  - [Socio-esthetics in geriatrics].

PMID- 20677496
TI  - [Giving back the feeling in geriatric grace to the project of living].

PMID- 20677497
TI  - [Concerning mistreatment and good treatment of the aged. Good treatment is a
      concern of everyone].

PMID- 20677498
TI  - [From the concept of mistreatment to that of positive treatment, a path full of
      pitfalls].
AB  - Mistreatment is a recent, "concrete" concept. Positive treatment is an even more
      recent, "vague" concept. While one is not the opposite of the other, it is
      impossible to study one without the other. Between passive tolerance and blind
      repression, there is room for reasoned, humble and comprehensive analysis which
      does not lose sight of the desire to care for others.

PMID- 20677499
TI  - [What are the different prospects for positive treatment?].
AB  - While the concept of positive treatment is undeniably fashionable, the manner in
      which it is replacing the concept of mistreatment raises questions. What is the
      significance of this semantic development and what should be deduced from this
      new term with regard to the effective development of professional practices?
      Three different prospects appear to await the term positive treatment:
      incarnating a figure of denial, acting as an asset, or infinitely more
      preferable, bringing about a questioning of professional practices. But this
      third prospect is not without its challenges: it cannot exist without managerial
      involvement focusing on the ethical requirements of positive treatment in terms
      of respect for people in care.

PMID- 20677500
TI  - [When positive treatment and skills coincide].
AB  - Due to a lack of sufficient knowledge of geriatrics, nurses working in other
      speciality departments are often poorly equipped when faced with certain elderly
      patients in particular those who are agitated or confused. These deficiencies can
      result in unsuitable treatment or even mistreatment. Continuing training and
      using mobile geriatrics liaison teams can help to foster the quality care and
      positive treatment of hospitalised elderly people.

PMID- 20677501
TI  - [Suffering in geriatrics and support for the healthcare supervisor].
AB  - Relational violence is often a component of the nurse/patient relationship in
      geriatrics. It stems from the suffering of elderly people on the one hand and of
      healthcare workers on the other. In this context, supporting the healthcare
      worker is essential.

PMID- 20677503
TI  - [Residents' feelings towards their care in temporary care homes].
AB  - Residents' feelings towards their care in temporary care homes. Elderly people
      cared for in institutions are obviously the best placed to talk about the quality
      of care and treatment they receive. As part of a positive treatment approach, it
      is the opinions of the residents themselves which carry most weight in assessing
      what they value most on a day-to-day basis. Results of a survey of voluntary
      residents in a temporary care home in the North of France.

PMID- 20677502
TI  - [Solres 92, one department's measure to support positive treatment].
AB  - Solres 92 is the benchmark scheme in the Hauts-de-Seine department for the
      national platform created to respond to the mistreatment of elderly or disabled
      people (3977). Since 2003, this association has provided mediation and prevention
      actions in order to support professionals in the field and families facing
      complex situations of mistreatment. Multidisciplinary reflection is a
      prerequisite to any recommendations.

PMID- 20677504
TI  - [Some thoughts about good treatment].
AB  - Could it be that the concept of positive treatment is losing ground? There is
      currently a real mistrust felt by some with regard to the concept. What are the
      reasons for this rejection?

PMID- 20677505
TI  - [3/11 The current geriatric court].

PMID- 20677506
TI  - [3/7 Lung cancer in the aged].

PMID- 20677507
TI  - [Good servants are found in Heaven].

PMID- 20677508
TI  - [Nurses between visions and obstacles].

PMID- 20677509
TI  - ["He should not break all the bones"].

PMID- 20677510
TI  - [Focusing for better education for geriatric nursing].

PMID- 20677511
TI  - ["We children know very well what helps us"].

PMID- 20677512
TI  - [Where the care chain carries no risk].

PMID- 20677513
TI  - ["Nurse stories have inspired me to write songs"].

PMID- 20677514
TI  - [The nursing society separates itself from the central agency].

PMID- 20677515
TI  - [A work accident, but not qualified as such].

PMID- 20677516
TI  - [Dealing with straightening one's own wishes].

PMID- 20677517
TI  - [The times, a subtle alliance].

PMID- 20677518
TI  - [Preserving immutable values].

PMID- 20677519
TI  - [Why is there so much bad feeling?].

PMID- 20677520
TI  - [Taking time is not getting lost!].

PMID- 20677521
TI  - [First district meeting of health professionals].

PMID- 20677522
TI  - [Interdisciplinary care at the center of debate].

PMID- 20677523
TI  - [A movie by Peter Luis. The trainee].

PMID- 20677524
TI  - [One hundred years of history: an outlook for the future].

PMID- 20677525
TI  - [Humanity and professionalism: a valuable impression].

PMID- 20677526
TI  - Naftifine, a topical allylamine.

PMID- 20677527
TI  - The manufacturer of the FDA approved non-resorbable aesthetic dermal filler
      Artefill.

PMID- 20677528
TI  - Systemic retinoids for chemoprevention of non-melanoma skin cancer in high-risk
      patients.
AB  - Patients at high risk for the development of multiple non-melanoma skin cancers,
      especially those receiving immunosuppressive medications following solid organ
      transplantation, are candidates for chemoprophylaxis. In patients where photo
      protection and topical medications are insufficient to prevent the growth of new
      cancers, there is considerable evidence that oral retinoids, including vitamin A,
      and synthetics such as isotretinoin, etretinate and acitretin are efficacious in
      this regard. This manuscript is a review of the literature regarding the use of
      these agents for chemoprophylaxis of non-melanoma skin cancer. Also included is
      anecdotal evidence that bexarotene, a rexinoid, may be as effective as acitretin
      in terms of chemoprevention, with a comparable side effects at doses recommended
      for chemoprophylaxis.

PMID- 20677530
TI  - The role of phototherapy in cutaneous T-cell lymphoma.
AB  - Cutaneous T-cell lymphoma (CTCL) is a type of non-Hodgkin's lymphoma
      characterized by the malignant proliferation of T lymphocytes in the skin.
      Phototherapy has been proven an effective treatment modality for CTCL, in
      particular early stage disease (patch and plaque). Specifically, broadband
      ultraviolet B (BB-UVB), psoralen and ultraviolet A (PUVA), and more recently
      narrowband UVB (NB-UVB) are the skin-directed phototherapies typically utilized.
      Phototherapy poses the risk of sunburn, photoaging and photocarcinogenesis.
      Combination therapies with IFN-alpha, retinoids (acitretin and isotretinoin) and
      rexinoid (bexarotene) are adjunctive systemic therapies that facilitate enhanced
      therapeutic response and often allow for lower doses of phototherapy.
      Extracorporeal photopheresis (ECP) has also been shown to be effective in more
      advanced stage disease.

PMID- 20677529
TI  - Advances in immunostains used in Mohs surgery.
AB  - In recent years, Mohs micrographic surgery (MMS) has become a widely utilized
      method of removal for a variety of cutaneous neoplasms. Certain clinical
      scenarios, however, make it difficult to visualize residual tumor cells,
      potentially decreasing the efficacy of the Mohs procedure. Immunohistochemical
      (IHC) stains are now available and are being utilized to delineate cells of
      interest intraoperatively when routinely stained slides are equivocal. While
      useful, IHC stains have not gained wide acceptance as an adjunct to MMS,
      particularly due to increased processing time, cost and workload required. There
      have been multiple recent advances, however, in the utilization of IHC stains in
      MMS. In this article, the authors discuss recent advances in IHC stains used in
      MMS for the treatment of melanoma as well as nonmelanoma skin cancers,
      potentially making their routine use in select cases more feasible.

PMID- 20677531
TI  - Controversies in skin surgery: electrodessication and curettage versus excision
      for low-risk, small, well-differentiated squamous cell carcinomas.
AB  - BACKGROUND: Electrodesiccation and curettage (ED&C) of low-risk, cutaneous
      squamous cell carcinoma (SCC) generally consumes less time and resources than
      excision. Review of the literature reveals few recent studies examining cure
      rates for ED&C in the treatment of low risk cutaneous SCC. OBJECTIVE: To evaluate
      via two retrospective studies the efficacy of ED&C in the treatment of low risk
      cutaneous SCC. METHODS: A small controlled study in a Veterans Administration
      teaching hospital dermatology clinic compared cure rates of low risk SCC at one
      year by ED&C to those of surgical excision. A second study examined the cure rate
      of low risk lesions treated by curettage and electrodesiccation in a private
      practice. RESULTS: The first study found no significant difference in cure rates
      between ED&C (14 of 14 cases successfully treated) and excision (15 of 16
      successfully treated and one recurrence) (P = 0.1711). The second study found the
      ED&C cure rate (106 of 106 successfully treated) to be significantly greater than
      an arbitrary cure rate of 95 percent (P = 0.0091). CONCLUSION: These findings
      support the efficacy of ED&C as a treatment modality for low-risk cutaneous SCC.

PMID- 20677532
TI  - Merkel cell carcinoma: clinical characteristics, markers, staging and treatment.
AB  - Merkel cell carcinoma (MCC) is a highly aggressive neoplasm affecting primarily
      the elderly Caucasian population. Earlier detection of this neoplasm may achieve
      a better prognosis and an improved outcome. Here, the authors review the typical
      clinical features of MCC to serve as a reference tool for clinicians in
      determining when a biopsy may be warranted. An array of immunohistochemical
      markers may be utilized to differentiate MCC from other neuroendocrine tumors.
      The staging and concomitant treatment options of MCC are discussed. In addition,
      the authors review therapeutic advances for treatment of MCC utilizing an array
      of target proteins.

PMID- 20677533
TI  - Mohs surgery for melanoma in situ: how we do it.
AB  - The advent of rapid immunostains has made the use of Mohs surgery to treat
      melanoma more practical. Mohs surgery is especially useful in the management of
      lentigo maligna, which often has indistinct clinical margins. The authors
      describe their technique for treating melanoma in situ with Mohs surgery.

PMID- 20677534
TI  - Discussing sentinel lymph node biopsy with your melanoma patients.
AB  - Sentinel lymph node biopsy, indicated for stage 1B/2 melanoma may be an
      underutilized diagnostic modality. Experts in the field agree that sentinel lymph
      node biopsy should be offered to patients with T1 melanomas with primary tumor
      ulceration, a mitotic rate greater than or equal to 1/mm2, and/or Clark level
      IV/V invasion especially if tumor thickness exceeds 0.75 mm. It is the
      responsibility of practitioners to characterize patients as eligible or non
      eligible for the sentinel node procedure. Furthermore, it is important to obtain
      a fully informed consent and explain to patients the statistics of the
      progonostic information garnered by the test.

PMID- 20677535
TI  - Relaxation strategies for patients during dermatologic surgery.
AB  - Patient stress and anxiety are common preoperatively and during dermatologic
      procedures and surgeries. Stress and anxiety can occasionally interfere with
      performance of procedures or surgery and can induce hemodynamic instability, such
      as elevated blood pressure or syncope, as well as producing considerable
      discomfort for some patients. Detection of excess stress and anxiety in patients
      can allow the opportunity for corrective or palliative measures. Slower
      breathing, biofeedback, progressive muscular relaxation, guided imagery,
      hypnosis, meditation and music can help calm and rebalance the patient's
      autonomic nervous system and immune functioning. Handheld miniaturized heart rate
      variability biofeedback devices are now available. The relaxation response can
      easily be taught. Guided imagery can be recorded or live. Live rapid induction
      hypnosis followed by deepening and then self-guided imagery requires no
      experience on the part of the patient but does require training and experience on
      the part of a provider. Recorded hypnosis inductions may also be used. Meditation
      generally requires more prior experience and training, but is useful when the
      patient already is skilled in it. Live, guided meditation or meditation
      recordings may be used. Relaxing recorded music from speakers or headphones or
      live performance music may also be employed to ease discomfort and improve the
      patient's attitude for dermatologic procedures and surgeries.

PMID- 20677536
TI  - The role of maintenance phototherapy in cutaneous T-cell lymphoma.
AB  - Phototherapy is well-recognized as effective therapy in early stage cutaneous T
      cell lymphoma (patch and plaque), often resulting in complete clearance of
      clinical disease and subsequent remission. Although not curable, long-term
      remission can often be attained utilizing maintenance phototherapy, consisting of
      a course of less frequent treatments over time. Herein, the authors review the
      literature regarding the role of maintenance phototherapy in cutaneous T-cell
      lymphoma (CTCL) and its success in prolonging clinical remission and disease-free
      survival in CTCL.

PMID- 20677537
TI  - Tretinoin gel microsphere pump 0.04% plus 5% benzoyl peroxide wash for treatment
      of acne vulgaris: morning/morning regimen is as effective and safe as
      morning/evening regimen.
AB  - Topical tretinoin and benzoyl peroxide (BPO) are often prescribed in combination
      for the treatment of acne vulgaris; however, these products have not
      traditionally been administered simultaneously because of the potential for
      tretinoin degradation by BPO as well as the instability of tretinoin in daylight.
      The primary objective of this randomized, investigator-blinded, 12-week, phase 4
      trial was to determine non-inferiority of a once-daily morning combination
      regimen of 5% BPO wash + tretinoin gel microsphere (TGM) 0.04% pump versus a
      sequential regimen (BPO in the morning/TGM in the evening) in patients > or = 12
      years old with moderate facial acne vulgaris. The primary efficacy endpoint was
      the change from baseline in total acne lesions; the primary safety endpoint was
      the change in cutaneous irritation scores. The 247 participants (mean age: 18.5
      years) were randomized to either the morning/morning regimen (n = 123) or the
      morning/evening regimen (n = 124). The morning/morning regimen was determined to
      be non-inferior to the morning/evening regimen in reduction of total acne
      lesions. The tolerability of both regimens was comparable. The morning/morning
      regimen is a safe and effective treatment option for patients with moderate acne
      vulgaris.

PMID- 20677538
TI  - Thalidomide and analogues: potential for immunomodulation of inflammatory and
      neoplastic dermatologic disorders.
AB  - Thalidomide and analogues are a class of immunomodulatory drugs or IMiDS.
      Thalidomide was initially approved by the U.S. Food and Drug Administation for
      treatment of erythema nodosum in leprosy and is now approved for multiple myeloma
      as well. A second generation IMiD, lenalidomide, is also approved for multiple
      myeloma and refractory myelodysplastic syndrome. Discovery of this class of drugs
      has been serendipitous and empirical, as the drug targets have been unknown. In
      this review, the authors integrate recent identification of drug targets of
      IMiDS, which include the inducible form of nitric oxide synthase (iNOS), Rho
      GTPase and caspase-1, with the developments in the understanding of the molecular
      biology of human inflammatory, infectious and neoplastic skin disorders. Because
      thalidomide reemerged through leprosy, the original disease classified by the T
      cell, the authors have also emphasized advances in the understanding of T-cell
      subsets in human skin disorders.

PMID- 20677539
TI  - Nephrogenic systemic fibrosis: a review.
AB  - Nephrogenic systemic fibrosis (NSF) is a recently described, debilitating
      systemic disease most commonly seen in patients with renal insufficiency.
      Exposure to gadolinium-containing contrast agent has been associated with the
      onset of symptoms. The epidemiology, pathogenesis, clinical manifestation,
      diagnosis, histolopathology, differential diagnosis and treatment will be
      reviewed. Clinicians should have a high index of suspicion in susceptible
      individuals.

PMID- 20677540
TI  - Case of fatal toxic epidermal necrolysis due to cardiac catheterization dye.
AB  - Cardiac catheterization is a very common procedure carried out for diagnostic as
      well as therapeutic reasons. Complications are not surprising due to the invasive
      nature of the procedure. Most of these complications have been seen numerous
      times by cardiologists who frequent the catheterization laboratory.
      Unfortunately, this patient experienced an extremely rare complication that
      ultimately resulted in his death. Here, the authors report a case of toxic
      epidermal necrolysis (TEN) resulting from the nonionic radiocontrast agent used
      in cardiac catheterization.

PMID- 20677541
TI  - Unilateral lichen planus pigmentosus mimicking acral lentiginous melanoma.
AB  - The authors report a case of a Latin American woman who developed progressive
      pigmentation primarily involving two digits of her right hand. She was scheduled
      for amputation based on a presumptive histologic diagnosis of melanoma with
      regression. Dermatology consultation with repeat biopsies disclosed a lichenoid
      tissue reaction with marked pigment incontinence and no evidence of melanoma.
      This report should prompt physicians to include lichen planus pigmentosus in the
      differential diagnosis of acral lentiginous melanoma.

PMID- 20677542
TI  - Familial pityriasis rubra pilaris: report of a family and therapeutic response to
      etanercept.
AB  - Pityriasis rubra pilaris (PRP) is an uncommon dermatosis of unknown etiology. The
      familial subtype is rare and usually presents as type V PRP. It is generally
      inherited in an autosomal dominant fashion with variable expression. Other forms
      of inheritance, such as autosomal recessive and X-linked, have also been
      reported. The use of etanercept in treating resistant forms of PRP is promising
      given reports of its success in a few cases. Herein, the authors report two cases
      of PRP arising in a mother and son and review the rare familial subtype of this
      disease. In addition, a successful therapeutic trial of etanercept was initiated
      in the mother based on case reports of its efficacy in other patients with PRP.

PMID- 20677543
TI  - Primary cutaneous angioimmunoblastic T-cell lymphoma histologically mimicking an
      inflammatory dermatosis.
AB  - Angioimmunoblastic T-cell lymphoma (AITL) is a systemic lymphoproliferative
      disease characterized by a polymorphous neoplastic infiltrate involving lymph
      nodes as well as extranodal locations, including the skin. Cutaneous involvement
      is seen in approximately 50 percent of cases and is usually secondary to systemic
      disease. Patients with cutaneous involvement classically present with a transient
      morbilliform eruption of the trunk; however, papules, nodules, urticarial plaques
      and erythroderma have also been reported. In contrast, primary cutaneous AITL is
      exceedingly rare. The authors report a case of a 79-year-old woman with AITL who
      presented with primary cutaneous tumors and ulcerated nodules, with no evidence
      of systemic involvement, hypergammaglobinemia, or B symptoms. Histologically, a
      subtle lymphoid infiltrate was present, dominated by marked fibrosis and a
      diffuse infiltrate of neutrophils, eosinophils and plasma cells, mimicking an
      inflammatory or infectious etiology. This presentation presents a unique
      diagnostic challenge; careful investigation and strong clinical suspicion must be
      utilized in order to correctly identify AITL in this setting.

PMID- 20677544
TI  - Case series: evaluation of a liquid silicone gel on scar appearance following
      excisional surgery--a pilot study.
AB  - Efforts to improve the size and appearance of scars have included therapies as
      varied as laser treatments and onion extract gels. Silicone gel sheeting is well
      know to improve the appearance of hypertrophic scars, and may have a role in the
      management of routine surgical and traumatic scars. By varying the degree of
      cross linking, silicone elastomer can be a solid sheet or a liquid gel. In this
      pilot series, seven patients applied a liquid silicone gel twice a day to one
      half of a new surgical scar for three months. At the end of this time, the
      treated side was noticeably better in appearance in five of seven patients while
      two of seven had no difference. In no patient was the silicone treated side worse
      in appearance.

PMID- 20677545
TI  - Warfarin-induced skin necrosis mimicking calciphylaxis: a case report and review
      of the literature.
AB  - Warfarin-induced skin necrosis (WISN) and calciphylaxis share similar early
      clinical findings and can both lead to significant morbidity and mortality. The
      authors reviewed the literature on both conditions and describe a case of
      extensive skin necrosis in a patient with end-stage renal disease who was
      initially suspected to have calciphylaxis. Further investigation supported a
      diagnosis of WISN. The pathogenesis, clinical manifestations and treatment of
      WISN and calciphylaxis are discussed, with emphasis on a diagnostic approach for
      early recognition.

PMID- 20677546
TI  - Case-based considerations in the treatment of actinic keratoses: utilizing
      combination or sequential therapy with 5-fluorouracil cream and destructive
      treatments.
AB  - Dermatologic conditions associated with prolonged sun exposure represent a
      substantial portion of visits to the dermatologist's office, particularly among
      elderly populations. Actinic keratoses are premalignant lesions that increase in
      frequency with each decade of life and have the potential to progress to squamous
      cell carcinoma. Non-melanoma skin cancers, such as squamous cell carcinoma and
      basal cell carcinoma, also represent sun-related conditions that require early
      and aggressive treatment. Therapeutic options for these conditions are abundant
      and range from topical field-directed therapies to destructive, lesion-directed
      procedures. Choice of therapy depends on the types and extent of lesions with
      which a patient presents; often, a combination of treatments provides the optimal
      means for successful outcomes. The following case-based review represents typical
      situations where multiple treatments were combined to manage actinic keratosis,
      squamous cell carcinoma and basal cell carcinoma in patients over an extended
      treatment period.

PMID- 20677547
TI  - Sclerotherapy update: polidocanol is approved in the United States.

PMID- 20677548
TI  - Nanotechnology and the Nanodermatology Society.
AB  - Nanotechnology is a rapidly developing discipline with enormous promise for
      consumers and patients. Currently, it is entering an inflection point in its
      growth phase--both in the number and diversity of products developed or soon to
      be available for society and medicine. It is no surprise that a vast number of
      patents have been issued for nanotechnology in the cosmetics arena as a means of
      enhancing topical delivery of a broad range of over-the-counter products. In
      fact, the skin is the first point of contact for a whole host of nanomaterials,
      ranging from topical preparations, articles of clothing and household products,
      to sporting goods and industrial manufactured goods. Very little is known about
      the safety aspects of the nano-engineered materials that are being released in
      the environment, as well as those in consumer and healthcare products.

PMID- 20677549
TI  - [Biological characteristics and antitumor activity of CIK cells activated by
      recombinant human fibronectin for human lung cancer cell lines in vitro].
AB  - BACKGROUND AND OBJECTIVE: The CIK cell is one of the most important means of the
      adoptive cellular immunotherapy, and it is a hotspot of which to simplify its
      culture procedure and to promote its inhibition rate. The aim of this study is to
      observe the biological function of the CIK cells cultivated by the recombinant
      human fibronectin (RN) and to establish an effective and simple way of cells
      expansion. METHODS: We separated the mononuclear cells (PBMCs) in 50 mL
      peripheral blood from 10 healthy persons with density gradient centrifugation in
      the lymphocyte-separating medium, and the PBMCs were divided into two groups, of
      which were cultivated by RN-introduced and conventional method separately. Then
      we estimated the proliferation ability, and analyzed the immunologic type, IFN
      gamma, IL-4, perforin and granzyme B of them with flow cytometry. Besides that,
      we tested the inhibition rate of CIKs cells to four kinds of human lung cancer
      cell lines in vitro by MTT assay. RESULTS: The RN-induced group had a higher
      proliferation rate that was 2.0-3.5 times of the conventional group, and there
      was an obvious statistical difference between the two (P < 0.05). The
      proliferation rates of CD3+CD16+CD56+T cells in each group were 3 778 and 2 068
      times of the initial number, respectively. There was also a higher percentage of
      CD3+CD8+ T cells in RN-induced group (P < 0.05), while the percentage of
      CD3+CD4+T cells had no significant statistical difference (P > 0.05). We found a
      similar inhibition rate of the CIK cells to all this human lung cancer cell lines
      (P > 0.05). The cells which secreted IFN-gamma increased, while the cells which
      secreted IL-4 did not. The cells which secreted granzyme B and perforin were
      positive. CONCLUSION: It is an effective and simple way to cultivate the CIK
      cells with RN, which should be adopted.

PMID- 20677550
TI  - [Identification of candidate genes for lung adenocarcinoma using Toppgene].
AB  - BACKGROUND AND OBJECTIVE: Lung adenocarcinoma (AC) is the most common type of
      lung cancer, however, its mechanism of oncongenesis is still unknown. The aim of
      this study is to screen candidate genes of lung adenocarcinoma using
      bioinformatics strategy and elucidate the mechanism of lung adenocarcinoma.
      METHODS: Two published microarray data (GSE7670 and GSE10072) was obtained from
      Gene Expression Omnibus (GEO). Significance analysis of microarrays was performed
      with the software dchip, and differential expression genes from dchip analysis
      were defined as "test gene set". Genes correlated with lung adenocarcinoma,
      obtained by data mining tools genecard and Fable were regarded as "train gene
      set". Finally, candidate genes of lung adenocarcinoma were screened by the tool
      "Toppgene". RESULTS: Three hundred and forty-four differential genes were defined
      as "test gene set", and 277 genes correlated with lung adenocarcinoma were
      regarded as "train gene set". Thirty-six candidate genes were screened out by
      Toppgene, among them, 21 genes had nearly no report in cancer. In the following
      QRT-PCR experiment, CD36, PMAIP1 and FABP4 were down-regulated expression in
      A549, which coincided with the gene chip. CONCLUSION: It is demonstrated that
      Toppgene is useful in identification of the candidate genes of lung
      adenocacinoma, which provides the proof for the discovery of the specific disease
      genes.

PMID- 20677551
TI  - [Resveratrol inhibits EGF-induced invasion of human lung adenocarcinoma A549
      cells].
AB  - BACKGROUND AND OBJECTIVE: Invasion and metastasis are the primary causes of death
      in patients with pulmonary carcinoma. The epidermal growth factor (EGF)
      stimulates A549 cells invasion greatly through activating ERK and PI3K-Akt
      signaling pathway. The aim of this study is to elucidate the inhibitory effect of
      Resveratrol on EGF-induced invasive ability of A549 cells in vitro and explore
      the molecular mechanism. METHODS: The cytotoxicity of Resveratrol was evaluated
      by methyl thiazolyltetrazolium (MTT) assay. Then, the A549 cells were treated
      with EGF and non-cytotoxic concentration of Resveratrol. The cells' invasion were
      detected by Boyden chamber assay; MMP-2 activity was determined by gelatine
      zymography assay; the changes of the related proteins were detected by Western
      blot. RESULTS: Resveratrol was not toxic to A549 cells at the concentration
      between 0 to 30 microM. The invasion ability of EGF-induced A549 cells was
      decreased after treatment with 20 microM resveratrol for 24 h, accompanied by the
      inhibition of MMP-2 secretion. And the levels of p-ERK1/2, PI3K (within 6 h) were
      suppressed too. CONCLUSION: 20 microM Resveratrol inhibits A549 cells' invasion
      possibly through the suppression of the activation of ERK and PI3K-Akt signaling
      pathways, subsequently exerting inhibitory effect on MMP-2.

PMID- 20677552
TI  - [Effect of liposomal transfection of UCH-L1 siRNA on proliferation and apoptosis
      of lung cancer cell line H157].
AB  - BACKGROUND AND OBJECTIVE: Several reports demonstrated that the ubiquitin C
      terminal hydrolase-L1 (UCH-L1) has been found to be an oncogene in malignant
      tumors such as esophageal carcinoma, lung cancer and breast cancer. The aim of
      this study is to explore the effects of liposomal transfection of UCH-L1 siRNA on
      the proliferation and apoptosis of lung adenocarcinoma cell lines H157. METHODS:
      UCH-L1 siRNA was synthesized and transfected into H157 cell by liposome. Cell
      morphological change was observed with microscope, and cell proliferation and
      apoptosis index detected by flow cytometry, UCH-L1 mRNA expression was determined
      by RT-PCR and protein level of UCH-L1 was determined by Western blot. RESULTS:
      For the H157 cell transfected with siRNA, cell proliferation was inhibited
      significantly, cell apoptosis appeared obviously, the expression of UCH-L1 mRNA
      and protein level of UCH-L1 significantly decreased. CONCLUSION: UCH-L1 siRNA is
      able to inhibit the proliferation of lung adenocarcinoma cell lines H157 and
      induce the apoptosis. UCH-L1 might become a new target for lung carcinoma gene
      therapy.

PMID- 20677553
TI  - [Expression of hTERT mRNA in Anip973 and Anip973/NVB cell detected by
      quantitative real-time PCR].
AB  - BACKGROUND AND OBJECTIVE: Human telomerase reverse transcriptase is the catalytic
      subunit of telomerase, and its activity is correlated with cell's sensitivity to
      chemotherapy. The aim of this study is to investigate the differential expression
      of human telomerase reverse transcriptase (hTERT) mRNA in human lung
      adenocarcinoma cell line Anip973 and Anip973/NVB, and to observe the correlation
      between hTERT mRNA and drug-resistance. METHODS: The real-time fluorescence
      quantitative RT-PCR was used to detect the change of hTERT mRNA in human lung
      adenocarcinoma drug-resistant cell Anip973/NVB and parental cell Anip973 treated
      by NVB. RESULTS: In the control group, the expression of hTERT mRNA showed no
      significant difference between drug-resistant cell Anip973/NVB and parental cell
      Anip973. After been treated by NVB, the expression of hTERT mRNA in parental cell
      was significantly decreased (P < 0.01), and drug-resistant cell Anip973/ NVB had
      no evidently variant (P > 0.05). The down-regulated hTERT mRNA in Anip973 cell
      was higher than that in Anip973/ NVB cell. CONCLUSION: Telomerase correlates with
      the drug-resistant cell A973/NVB, and telomerase may be a new target for multi
      drug resistant inversion.

PMID- 20677555
TI  - [99Tc(m) -N(NOEt)2 uptake kinetics difference among KMB17 human embryonic lung
      diploid fibroblast and different human lung cancer cells].
AB  - BACKGROUND AND OBJECTIVE: PET/CT imaging is expensive, so searching the tumor
      imaging agent for SPECT/CT is necessary. 99Tc(m) -N(NOEt)2 [bis (N-ethoxy-N-ethyl
      dithiocarbamato) nitrido 99Tc(m) (V)] can be uptaken by lung cancer cells and
      other cells alike. The aim of this study is to evaluate the distinctive value in
      lung tumor with 99Tc(m) -N(NOEt)2, the difference in its uptake kinetics in human
      embryonic lung diploid fibroblasts KMB17 and several kinds of lung cancer cells
      lines. METHODS: Firstly, six different cell culture medium which contained YTMLC
      Gejiu human lung squamous carcinoma cell, SPC-A1 human lung adenocarcinoma cell,
      AGZY low metastatic human lung adenocarcinoma, 973 high metastatic human lung
      adenocarcinoma cell, GLC-82 Gejiu human lung adenocarcinoma cell, and KMB17 human
      embryonic lung diploid fibroblast, respectively with equal cell density of 1 x
      10(6)/mL and the same volume were prepared; secondly, the same radioactive dose
      of 99Tc(m) -N(NOEt)2 was added into each sample and then 300 microL mixed sample
      was taken out respectively and cultured in 37 degrees C culture box; Finally, 5
      min, 15 min, 30 min, 45 min, 60 min, 75 min, 90 min after cultivation,
      centrifuged each cultured sample and determined the intracellular radiocounts of
      each sample, calculated each cell sample's uptake rate of 99Tc(m) -N(NOEt)2 at
      different time. RESULTS: Statistical difference was found among six cell samples,
      and the uptake rate sequence from high to low is 973 and SPC-A1 > YTMLC > GLC-82
      > AGZY > KMB17 respectively; furthermore, 30 min-45 min after culture, the uptake
      rate reached stability, and the 45 min uptake rate of each sample was higher than
      its 96.7% uptake peak. CONCLUSION: Based on the results above mentioned, it is
      supposed that there are discriminative clinical value when using 99Tc(m) 
      N(NOEt)2 as a tumor targeting imaging agent, and 30 min or so after injection may
      be the best imaging time in the early imaging stage.

PMID- 20677554
TI  - [Curcumin promoted the apoptosis of cisplain-resistant human lung carcinoma cells
      A549/DDP through down-regulating miR-186*].
AB  - BACKGROUND AND OBJECTIVE: Curcumin, a natural compound, is derived from the
      rthizom of Curcuma longa. In vitro and in vivo preclinical studies have shown its
      anti-inflammatory, antioxidant, anticancer activities and so on. miR-186*, which
      was found by microarray technology, was highly expressed in lung carcinoma cells
      A549/DDP. The aim of this study is to illustrate whether Curcumin could promote
      the apoptosis of A549/DDP cells through regulating the expression of miR-186*.
      METHODS: An oligonucleotide microarray chip was used to profile microRNA (miRNA)
      expressions in A549/DDP cells treated with and without Curcumin. The
      significantly differentially expressed miRNA, which was selected from microarray
      chip, validated by quantitative real-time PCR. Ultimately, the remarkably
      expressed miRNA modulated the apoptosis assaying by flow cytometry expriments and
      the survival rate was measured by MTT method. RESULTS: The microarray chip
      results demonstrated: Curcumin altered the expression level of miRNAs compared
      with untreated control in A549/DDP cell line, miR-186* was significantly down
      regulated after Curcumin treatment, which confirmed by quantitative real-time
      PCR. Down-regulation of miR-186* expression by curcumin elevated the apoptosis,
      and the survival rate of A549/DDP cells decreased; but up-regulation of miR-186*
      expression by transfection its mimics restrained the apoptosis, the survival rate
      of A549/DDP cells increased, which were assayed by flow cytometry expriments and
      MTT method. CONCLUSION: Modulation of miRNAs expression may be an important
      mechanism underlying the biological roles of Curcumin.

PMID- 20677556
TI  - [Prognostic value of methylation status of RASSF1A gene as an independent factor
      of non-small cell lung cancer].
AB  - BACKGROUND AND OBJECTIVE: Promoter hypermethylation of the RASSF1A gene is among
      the most abundant epigenetic deregulations in human cancer. The aim of this study
      is to investigate the relationship between the methylation status of RASSF1A
      promoter and the prognoses of non-small cell lung cancer (NSCLC). METHODS: The
      methylation status of RASSF1A promoter in 150 NSCLC and 25 non-malignant tissues
      was determined using a methylation-specific polymerase chain reaction (MSP).
      RESULTS: RASSF1A promoter hypermethylation was detected in 38.7% (58/150) of
      NSCLC tissues, but in none of the non-malignant tissues. The patients with
      hypermethylation of RASSF1A had a poor survival rate, and the relationship
      between the survival rate and hypermethylation of RASSF1A was statistically
      significant (P = 0.004). Then by using stepwise Cox proportional hazard
      regression testing, methylation status of RASSF1A was an independent factor
      affecting the NSCLC patients' survival (RR = 1.584, 95% CI: 1.040-2.411, P =
      0.032). CONCLUSION: The hypermethylation of the RASSF1A promoter may be an
      independent prognostic factor of NSCLC after operation.

PMID- 20677558
TI  - [cDNA microarray technique on screening multi-drug resistance-related genes of
      human non-small cell lung cancer].
AB  - BACKGROUND AND OBJECTIVE: The aim of this study is to screen for multi-drug
      resistance-related genes of human non-small cell lung cancer (NSCLC), and provide
      the evidences for drug-sensitive predicting genes of different NSCLC patients
      treated with chemotherapeutic drugs. METHODS: Sensitivity and inhibition ratio of
      five antitumor drugs (NVB, GEM, TAL, DOC, CDDP) on 75 fresh NSCLC samples from
      different individuals were studied by means of culturing primary tumor cells and
      MTT assay. After the five chemotherapeutic drugs were used, multi-drug resistance
      related genes of NSCLC with cDNA microarry on the samples which were all high
      sensitive and those resistant were screened. RESULTS: cDNA microarray analysis
      screened out 212 genes, 168 of which were up-regulated while the other 44 were
      down-regulated in the group of highly sensitive compared with the group of
      resistance. CONCLUSION: The multi-drug resistance of NSCLC may be correlative
      with the 212 genes screened by cDNA microarray; the detailed mechanisms of the
      genes still need to be detected in the future.

PMID- 20677557
TI  - [Expression and clinicopathologic significance of human achaete-scute homolog 1
      in pulmonary neuroendocrine tumors].
AB  - BACKGROUND AND OBJECTIVE: Human achaete-scute homolog 1 (hASH1) gene plays a
      critical role in development of the central nervous system, automatic nervous
      system, adrenal medullary chromaffin cells, thyroid C cells and pulmonary
      neuroendocrine cells. The aim of this study is to determine hASH1 gene expression
      in the normal lung tissue and various types of lung tumors, to analyze whether
      its expression correlated with pulmonary neuroendocrine markers, and to explore
      the possibility of hASH1 as clinical pathological markers in the neuroendocrine
      tumors compared with previous neuroendocrine tumor markers. METHODS: hASH1,
      Chromogranin A, Synaptophysin and CD56 expression were examined in lung tumor
      specimens (lung inflammatory pseudotumor, squamous cell carcinoma,
      adenocarcinomas, large cell carcinoma, typical carcinoids, atypical carcinoids,
      large cell neuroendocrine carcinomas and small cell lung carcinoma and
      corresponding normal lung specimens) using immunohistochemistry (S-P method).
      Western blot and reverse transcription polymerase chain reaction (RT-PCR) assay
      were applied to detect the expressions of hASH1 protein and mRNA in lung cancer
      tissues. RESULTS: hASH1 expression was positive in 2/16 (12.5%) typical
      carcinoids, 15/20 (75%) atypical carcinoids, 6/10 (60%) large cell neuroendocrine
      carcinomas and 31/40 (77.5%) small cell lung carcinoma, respectively, but not in
      any normal lung tissue (0/10), lung inflammatory pseudotumor (0/49), squamous
      cell carcinoma (0/30), adenocarcinomas (0/30) or large cell carcinoma (0/20).
      There was a significant difference in hASH1 expression between typical carcinoids
      and atypical carcinoids (P < 0.01), but not in large cell neuroendocrine
      carcinomas and small cell lung carcinoma (P > 0.05). hASH1 expression highly
      closely correlated with Chromogranin A, Synaptophysin and CD56 expression (P <
      0.05). CONCLUSION: hASH1 is a new kind of highly specific markers of pulmonary
      neuroendocrine tumours, and may be applied to clinical pathology diagnosis of the
      pulmonary neuroendocrine tumors.

PMID- 20677559
TI  - [Comparative analysis of clinical epidemiology and pathological characteristics
      of 908 patients with primary lung cancer of Hunan Province in 1997 and 2007].
AB  - BACKGROUND AND OBJECTIVE: Epidemiology of lung cancer will be changed along with
      time and region. The aim of this study is to acknowledge the tendency of primary
      lung cancer in hunan province in recent years by comparing and analyzing the
      distribution of gender, age, area, smoking and pathology of patients who were
      initial diagnosed lung cancer and ancestral or permanent residence of hunan
      province in 1997 and 2007. METHODS: Clinical data of 908 patients with primary
      lung cancer hospitalized in Xiangya hospital were collected and evaluated.
      RESULTS: Compared patients in 2007 with those in 1997, ratio between male and
      female dropped from 3.8:1 to 2.98:1, while the proportion of young patients who
      were under 40 years old raised from 4.4% to 8.6% (chi2 = 4.465, P = 0.035),
      patients living in the county raised from 19.9% to 40.1% (chi2 = 30.670, P <
      0.001), smoking rate of patients from county raised from 16.9% to 39.9% (chi2 =
      24.939, P < 0.01). In addition, the proportion of rare histological types of lung
      cancer were also increased from 1.3% to 4.5% (chi2 = 5.142, P = 0.023).
      CONCLUSION: Female patients, young patients, rural patients and rare histological
      types of lung cancer may have a tendency of increase in hunan province in recent
      years, whereas smoking cessation education should be strengthened.

PMID- 20677560
TI  - [The systemic evaluation and clinical significance of immunological function for
      advanced lung cancer patients].
AB  - BACKGROUND AND OBJECTIVE: The actual evaluation of immunological function is
      significant for studing the tumor development and devising a treatment in time.
      The aim of this study is to evaluate the immunological function of advanced lung
      cancer patients systematically, and to discuss the clinical significance.
      METHODS: The nucleated cell amounts of advanced lung cancer patients and the
      healthy individuals were counted. The immune cell subsets and the levels of IL-4,
      INF-gamma, perforin and granzyme in CD8+T cells by the flow cytometry were
      measured. The proliferation activity and the inhibition ratio of immune cells to
      several tumor cell lines were evaluated by MTT assay. RESULTS: The absolute
      amounts and subsets of T, B, NK cells of advanced lung cancer patients were lower
      than the healthy individuals (P < 0.05); However, the proportion of regulatory T
      cells of advanced lung cancer patients (4.00 +/- 1.84)% was lower than the
      healthy individuals (1.27 +/- 0.78)% (P < 0.05). The positive rates of IFN-gamma
      perforin, granzyme in CD8+T cells decreased while them in IL-4 did not in the
      advanced lung cancer patients compared to the healthy control group (P < 0.05).
      The proliferation activity of immune cells, the positive rate of PPD masculine
      and the inhibition ratio to tumor cells in the advanced lung cancer patients was
      lower than the healthy subsets obviously (P < 0.05). CONCLUSION: There was a
      significant immune depression in the advanced lung cancer patients compared to
      the healthy individuals.

PMID- 20677562
TI  - Surgical therapeutic strategy for non-small cell lung cancer with mediastinal
      lymph node metastasis (N2).
AB  - BACKGROUND AND OBJECTIVE: Approximately 30% of patients who are diagnosed with
      non-small cell lung cancer (NSCLC) are classified as N2 on the basis of
      metastasis to the mediastinal lymph nodes. The effectiveness of surgery for these
      patients remains controversial. Although surgeries in recent years are proved to
      be effective to some extent, yet due to many reasons, 5-year survival rate after
      surgery varies greatly from patient to patient. Thus it is necessary to select
      patients who have a high probability of being be cured through an operation, who
      are suitable to receive surgery and the best surgical methods so as to figure out
      the conditions under which surgical treatment can be chosen and the factors that
      may influence prognosis. METHODS: 165 out of 173 patients with N2 NSCLC were
      treated with surgery in our department from January 1999 to May 2003, among whom
      130 were male, 43 female and the sex ratio was 3:1, average age 53, ranging from
      29 to 79. The database covers the patients' complete medical history including
      the information of their age, sex, location and size of tumor, date of operation,
      surgical methods, histologic diagnosis, clinical stage, post-operative TNM stage,
      neoadjuvant treatment and chemoradiotherapy. The methods of clinical stage
      verification include chest X-ray, chest CT, PET, mediastinoscopy, bronchoscope
      (+?), brain CT or MRI, abdominal B ultrasound (or CT), and bone ECT. The
      pathological classification was based on the international standard for lung
      cancer (UICC 1997). Survival time was analyzed from the operation date to May
      2008 with the aid of SPSS (Statistical Package for the Social Sciences) program.
      Kaplan-Meier survival analysis, Log-rank test and Cox multiplicity were adopted
      respectively to obtain patients' survival curve, survival rate and the impact
      possible factors may have on their survival rate. RESULTS: The median survival
      time was 22 months, with 3-year survival rate reaching 28.1% and 5-year survival
      rate reaching 19.0%. Age, sex, different histological classification and
      postoperative chemoradiotherapy seem to have no correlation with 5-year survival
      rate. In all N2 subtypes, 5-year survival rate is remarkably higher for
      unexpected N2 discovered at thoractomy and proven N2 stage before preoperative
      work-up and receive a mediastinal down-staging after induction therapy (P <
      0.01), reaching 30.4% and 27.3% respectively. 5-year survival rate for single
      station lymph node metastasis were 27.8%, much higher compared with 9.3% for
      multiple stations (P < 0.001). Induction therapy which downstages proven N2 in
      73.3% patients gains them the opportunity of surgery. The 5-year survival rate
      were 23.6% and 13.0% for patients who had complete resection and those who had
      incomplete resection (P < 0.001). Patients who underwent lobectomy (23.2%) have
      higher survival rate, less incidence rate of complication and mortality rate,
      compared with pneumonectomy (14.8%) (P < 0.01). T4 patients has a 5-year survival
      rate as low as 11.1%, much less than T1 (31.5%) and T2 (24.3%) patients (P =
      0.01). It is noted through Cox analysis that completeness of resection, number of
      positive lymph node stations and primary T status have significant correlativity
      with 5-year survival rate. CONCLUSION: It is suggested that surgery (lobectomy
      preferentially) is the best solution for T1 and T2 with primary tumor have not
      invaded pleura or the distance to carina of trachea no less than 2 cm, unexpected
      N2 discovered at thoractomy when a complete resection can be applied, and proven
      N2 discovered during preoperative work-up and is down-staged after induction
      therapy. Surgical treatment is the best option, lobectomy should be prioritized
      in operational methods since ise rate of complication and morality are lower than
      that of pneumonectomy. Patients' survival time will not benefit from surgery if
      they are with lymph nodes metastasis of multiple stations (Bulky N2 included) and
      T4 which can be partially removed. Neoadjuvant chemotherapy increases long-term
      survival rate of those with N2 proven prior to surgery. However, postoperative
      radiotherapy decreases local recurrence rate but does not contribute to patients'
      long-term survival rate.

PMID- 20677561
TI  - [Association between polymorphisms of ERCC1 and response in patients with
      advanced non-small cell lung cancer receiving cisplatin-based chemotherapy].
AB  - BACKGROUND AND OBJECTIVE: Results of studies on genetic polymorphisms of ERCC1
      gene in DNA repair pathway which may affect response to platinum-based
      chemotherapy and survival in patients with non-small cell lung cancer are
      conflicting. The aim of this study is to prospectively assess the association
      between single nucleotide polymorphisms of C8092A and codon118 in ERCC1 and drug
      response in 90 patients with advanced non-small cell lung cancer treated with
      cisplatin-based chemotherapy. METHODS: All patients were treated with cisplatin
      based chemotherapy. Genotypes of ERCC1 C8092A and codon118 were examined by
      sequencing, and the association between genotypes and response was evaluated.
      RESULTS: Genotype frequencies of ERCC1 C8092A were CC 40.0% (36/90), CA 48.9%
      (44/90) and AA 11.1% (10/90), frequencies of codon118 were CC 58.9% (53/90), CT
      34.4% (31/90) and TT 6.7% (6/90). There was no significant difference in response
      rate of patients carrying with CC, compared with CA plus AA in C8092A (33.3% vs
      29.6%, P = 0.71). Response rate of patients carrying with CC in ERCC1 118 was
      32.1%, 24.3% with CT plus CC (P = 0.43). There was no difference in progression
      free survival between patients carrying with CC and CT plus TT in C8092A (5.2
      months vs 5.4 months, P = 0.62). There was no difference in progression free
      survival between patients carrying with CC and CA plus AA (5.5 months vs 5.3
      months, P = 0.59). CONCLUSION: The results suggest that there is no association
      between polymorphisms in ERCC1 C8092A and codon118 and response in patients with
      advanced non-small cell lung cancer receiving cisplatin-based chemotherapy.

PMID- 20677563
TI  - Diagnostic value of sialic acid in pleural effusion.
AB  - The present study was conducted in 30 patients of malignant pleural effusion and
      30 patients of non malignant pleural effusion. Pleural fluid and blood samples
      were taken at the time of admission, before starting any treatment. Sialic acid
      levels were estimated in serum and pleural fluid by Warren's TBA method. In the
      present study, serum sialic acid levels were higher in group II as compared to
      group I. In the present study, pleural fluid sialic acid levels and PF/S ratio
      was higher in malignant pleural effusion (though difference was not statistically
      significant). Smokers in group II had higher serum sialic acid as compared to
      group 1 (P < 0.05). The sensitivity and specificity of pleural fluid/serum sialic
      acid ratio with cut off value of 0.7 were 76.67% and 20% respectively, while
      taking the cut off value of 70 mg/dL for pleural fluid sialic acid in malignant
      pleural effusions, the sensitivity was 63.33%, specificity 60% and positive
      predictive value 46.34%. These findings indicate that determination of sialic
      acid levels in pleural fluid has diagnostic value as a cheap, simple and reliable
      marker for malignant pleural effusion.

PMID- 20677564
TI  - Tracheal carinal reconstruction and bronchovasculoplasty in central type
      bronchogenic carcinoma.
AB  - BACKGROUND AND OBJECTIVE: Because radical resection for lung cancer invading the
      initial borderline of different lobes and carina is difficult, we tried to
      analyse the variables of successful tracheal carinoplasty and
      bronchovasculoplasty to discover a proper approach for appropriate early and long
      term results. METHODS: Of 1 399 lung resections for primary lung cancer performed
      in our hospital from April 1985 to December 2006, 133 underwent bronchoplastic
      surgeries, including 15 carinoplasty cases and 118 sleeve lobectomy (SL) cases,
      and 118 pneumoectomy (PN) cases were compared at the same time. RESULTS:
      Complications occurred in 18 cases, with no operative related mortality. For all
      patients, the 1 year, 3 year, and 5 year survival rates were 79.8%, 56.7% and
      31.2%, respectively. The 5 year survival rate by cancer stage was 69.2% for Ib,
      40.6% for IIb, 19.6% for IIIa, and 16.6% for IIIa (N2). CONCLUSION: Selection of
      cases, clearance of lymph nodes, disposal of the bronchus and pulmonary vessel
      and replacement or restoration of the superior vena cava are the main factors
      influencing prognosis.

PMID- 20677565
TI  - [Clinical application of adjuvant treatment after operation in patients with
      stage IIIa non-small cell lung cancer].
AB  - BACKGROUND AND OBJECTIVE: The efficacy of complete resection of the cancer for
      patients with stage IIIa non-small cell lung cancer (NSCLC) is limited. Synthetic
      therapy is taken the lead in advocating at present. However, the value of post
      operative radiotherapy is not still clear. The aim of this study is to evaluate
      the survival time and side effects of postoperative chemotherapy or
      chemoradiotherapy in the treatment of stage IIIa NSCLC. METHODS: Between December
      2003 and June 2007, 52 cases that have completed followed-up data with stage IIIa
      of NSCLC received in the First Affiliated Hospital of Dahan Medical University.
      Twenty-three patients received postoperative chemoradiotherapy (group A) and 29
      patients received postoperative chemotherapy combined with radiotherapy (group
      B). Group A adopted platinum-based combination chemotherapy for 4-6 cycles. The
      chemotherapeutics included gemcitabine, vinorelbine and docetaxel. Group B used
      chemotherapy for 2-4 cycles and then received 3-dimensional conformal
      radiotherapy (3D-CRT). The prescribe dose of target volume was 50 Gy. The
      chemotherapy was same as for group A and needed 4 cycles in all. The impact of
      postoperative adjuvant treatment on survival and toxicity was observed in
      patients with stage IIIa NSCLC and the reason of disease progression was
      analyzed. RESULTS: The median survival was 32.5 months in group A and 31.9 months
      in group B (P = 0.371). Progression-free survival extended about 6 months (P =
      0.044). The survival rate was 87% at 1 year, 0.1% at 2 year, 33% at 3 year for
      group A compared with 93%, 69%, 45% for group B. The major side effects were
      hematological and gastrointestinal toxicities, including nausea, vomiting and
      neutropenia. There was no significant difference in these toxicities between the
      two groups (P > 0.05). Radioactive esophageal infection occurred in 17.2% of the
      patients. Acute and late radioactive lung infection occurred in 13.8% and 27.6%
      of the patients. All these toxicities were below degree 2. Distant metastases
      were the main reason of disease progression. There was no significant difference
      in the rates of local recurrence and metastases between the two groups (P >
      0.05). CONCLUSION: Combined modality therapy should be the main therapy of stage
      IIIa NSCLC. The addition of radiotherapy can effectively prolong progression-free
      survival and don't highly increase the toxicities.

PMID- 20677566
TI  - [A review of epidermal growth factor receptor/HER2 inhibitors in the treatment of
      patients with non-small-cell lung cancer].

PMID- 20677567
TI  - [The current research feature and prospect of bronchoalveolar lavage in
      diagnosing lung cancer].

PMID- 20677568
TI  - [The predictive value of EGFR status in non-small cell lung cancer patients
      treated with EGFR-TKIs].
AB  - Epidermal growth factor receptor (EGFR) is a major molecular for target therapy.
      The epidermal growth factor receptor tyrosine kinase inhibitors (TKIs), gefitinib
      (Iressa) and erlotinib (Tarceva), are two prospective agents towards non-small
      cell lung cancer (NSCLC). Multi-center clinical studies showed that there were
      obvious differences between individuals by the treatment of EGFR-TKIs. EGFR
      status is the major factor that influences the outcome for the treatment by TKI.
      Exon mutations and amplification of EGFR molecule are the critical factors that
      predict good response to TKIs. On the other hand, KRAS mutations indicate the
      resistant to the TKIs.

PMID- 20677569
TI  - [MicroRNA and lung cancer].

PMID- 20677570
TI  - [Effects of rh-endostar in combination with radiotherapy on rats with lung
      cancer].
AB  - BACKGROUND AND OBJECTIVE: Radiation sensitivity is closely related to tissue
      oxygen, and rh-endostatin can induce the high level of oxygen content in tumor by
      "normalizing" tumor angiogenesis which is associated with radiotherapy
      sensitivity. The aim of this study is to observe the effect of combination of
      radiotherapy with rh-endostatin in the rats with lung cancer. METHODS: Immediate
      lewis cancerous ascetic injection method was used to make rats tumors bearing
      model, then the rats was divided into four groups randomly: group A was treated
      with saline; group B was treated with rh-endostatin; group C was treated with
      irradiation and group D was treated with rh-endostatin and irradiation. After all
      rats were treated, inhibition rates and the tumor growth curve were calculated.
      Immunohistochemisty was adopted to check the expressions of vascular endothelial
      growth factor (VEGF) and microvessel density (MVD). RESULTS: Compared with group
      A, the growth rates of the tumors in the other group were obviously slower, and
      the tumor weights were significantly different form group A (P < 0.05). Compared
      with the other groups, the tumor weights of group D were obviously reduced (P <
      0.05). Compared with group A, VEGF and MVD of other three groups were reduced (P
      < 0.05), and group D were significantly cut down. CONCLUSION: Combination with
      radiotherapy and rh-endostatin could inhibit the lung cancer significantly in
      rats. The possible mechanisms are to decrease the expression ofVEGF and inhibit
      the production of angiogenesis.

PMID- 20677573
TI  - [Antibiotics and artificial nutrition in the cardiac intensive care unit].
AB  - Patients admitted to cardiac intensive care units are at high risk for
      infections, particularly nosocomial pneumonia, pacemaker's pocket and sternotomic
      wound infections. These complications delay recovery, prolong hospitalization,
      time on mechanical ventilation, and increase mortality. Both behavioral and
      pharmacological measures are needed to prevent and control infections in these
      patients, as well as specific antibiotic treatment and nutritional support. In
      infected critically ill patients, pathophysiological alterations modify
      distribution and clearance of antibiotics, and hypercatabolic state leads to
      malnutrition and immune paralysis, which both contribute to increased infectious
      risk and worsened outcome. A deep understanding of antibacterial agents
      pharmacology in the critically ill is essential in order to treat severe
      infections; moreover, it is necessary to know routes of administration and
      composition of artificial nutrition solutions. The aim of this review is to
      define main and specific aspects of antibiotic therapy and nutritional support in
      cardiac critical care patients in light of recent literature data.

PMID- 20677574
TI  - [Ventricular preexcitation: is risk stratification feasible?].
AB  - The Wolff-Parkinson-White syndrome is a current debated clinical issue. Although
      the anatomical characteristics, polymorphic electrocardiographic features, and
      electrophysiological mechanisms of arrhythmias and sudden cardiac death are well
      known, the identification of patients at risk of sudden cardiac death remains
      challenging. Owing to the lack of effective therapeutic strategies, in the pre
      ablation era many studies have been conducted to define the prognostic value of
      clinical and instrumental tests, and to define the actual risk of sudden cardiac
      death in patients with ventricular preexcitation. Nowadays, radiofrequency
      transcatheter ablation of anomalous atrioventricular pathways is a strong
      therapeutic option for all patients, independent of the risk of sudden cardiac
      death. However, radiofrequency ablation is associated with serious complications,
      but many studies confirm an overall good prognosis for most of the patients with
      electrocardiographic pattern of ventricular preexcitation. The aim of this review
      is to assess the prognostic value of clinical and instrumental tests in patients
      with ventricular preexcitation, referring to the latest knowledge.

PMID- 20677575
TI  - [Cardiac resynchronization therapy with defibrillation capability: considerations
      on a not yet proven therapeutic superiority].
AB  - Cardiac resynchronization therapy (CRT) has proven a very useful tool to treat
      heart failure (HF). In HF patients with severely depressed left ventricular
      dysfunction and ventricular dyssynchrony who remain symptomatic despite optimal
      medical therapy, the "reverse remodeling" induced by CRT leads to a significant
      improvement of survival and quality of life. The addition of the cardioversion
      defibrillation function to CRT (CRT-D) is considered a further beneficial effect
      to reduce overall mortality secondary to a decrease in sudden death rate.
      Unfortunately, the amount of this additional benefit is still uncertain; in
      particular, how much the cardioversion-defibrillation function contributes to
      prolong patient survival remains to be elucidated. Such uncertainty leads to a
      different therapeutic approach to HF patients, i.e., an extended or restricted
      use of CRT-D devices. Even the most recent guidelines do not provide a clear
      answer to this question. The present review summarizes the current evidence
      regarding efficacy, effectiveness, safety, and cost-effectiveness of CRT and CRT
      D, and suggests some practical solutions to the appropriate use of CRT-D on the
      basis of clinical, ethical and socio-economic considerations.

PMID- 20677576
TI  - [Cardiac resynchronization therapy with or without defibrillation backup:
      everything has been written?].

PMID- 20677577
TI  - [A controversy about the eponymous "second degree atrioventricular block" between
      Wenckebach, Luciani, Hay and Mobitz].

PMID- 20677578
TI  - [Nonvalvular atrial fibrillation: thromboembolic risk assessment and therapy in a
      general practice population].
AB  - BACKGROUND: Cardiologists may prescribe antithrombotic therapy to patients with
      atrial fibrillation (AF), but prescription application mostly depends on general
      practitioners. The present study aims to assess frequency and appropriateness of
      antithrombotic therapy in general practice, as a function of thromboembolic risk
      factors, using the CHADS2 score. METHODS: The computer records of 39 general
      practitioners were evaluated in order to identify patients with non-valvular AF;
      therapy and thromboembolic risk factors were recorded. RESULTS: AF was documented
      in 951 patients; 96 (10.1%) had contraindications to oral anticoagulants. Among
      the remaining 850 patients, 292 (34.4%) did not receive antithrombotic therapy
      according to guidelines. In particular, 102 (12.0%) did not receive any
      antithrombotic treatment. CONCLUSIONS: Among general practitioners of the Veneto
      region (Italy), the application of guidelines on antithrombotic therapy in non
      valvular AF is comparable, or even slightly better than that reported in
      published cohort studies, but it deserves further improvement. There is a need
      for targeted educational interventions and a better coordination between
      cardiologists and general practitioners.

PMID- 20677579
TI  - [Mitral valve prolapse and parasystolic ventricular tachycardia: an unusual
      association].
AB  - Ventricular arrhythmias are common in patients with mitral valve prolapse.
      Conversely, parasystolic ventricular tachycardia is an uncommon arrhythmia that
      can be observed independent of preexisting heart disease. We report the case of
      an otherwise healthy 42-year-old woman with both mitral valve prolapse and
      parasystolic ventricular tachycardia.

PMID- 20677580
TI  - [Transvenous removal of pacing leads in a complex patient with septicemia and a
      large endocarditic vegetation: a case report].

PMID- 20677581
TI  - [The Syncope Unit: a new organizational model for the management of patients with
      syncope].

PMID- 20677582
TI  - [Management of patients with palpitations. Consensus document of the AIAC
      (Italian Association of Arrhythmiology and Cardiostimulation].

PMID- 20677583
TI  - Lacosamide, a newer antiepileptic.
AB  - Lacosamide (LCM) is a newer antiepileptic drug with a dual mode of action. It
      selectively enhances slow inactivation of voltage-gated sodium channels without
      affecting fast inactivation, and modulates collapsing response mediator protein 2
      (CRMP-2). It has a high oral bioavailability of approximately 100%. It has shown
      potent and broad neuroprotective effects in vitro and in vivo animal models
      making it a potential candidate for long term treatment of epilepsy. In addition
      to this, it has demonstrated analgesic activity in various animal models. Apart
      from this, LCM has demonstrated potent effects in animal models for a variety of
      CNS disorders like schizophrenia and stress induced anxiety. Various safety
      pharmacology and toxicology studies have shown that LCM is well tolerated.
      Clinical trials have also suggested that LCM is a safe, effective, and well
      tolerated adjunctive treatment for reduction of seizure frequency in patients
      with highly refractory, partial seizures. Other potential indications of LCM are
      being investigated.

PMID- 20677584
TI  - Postoperative pain and respiratory function in patients treated with
      electroacupuncture following coronary surgery.
AB  - OBJECTIVES: To evaluate respiratory function and pain score in patients
      undergoing coronary bypass procedures during the first 7 postoperative days.
      METHODS: The study was carried out as a case-control study between April 2008 and
      April 2009 in the Department of Cardiovascular Surgery, Firat University Faculty
      of Medicine, Elazig, Turkey. Thirty patients, who had undergone a median
      sternotomy (MS) for coronary artery bypass graft, were randomized to either the
      electroacupuncture and pharmacologic analgesia (acupuncture) group, or the
      pharmacologic analgesia alone (control) group. In each group, severity of pain,
      analgesic intake, respiratory function, and pulmonary complications were
      recorded. Pethidine hydrochloride and metamizole sodium were administered.
      RESULTS: Of the 30 subjects, 15 were in the control group and 15 in the
      acupuncture group. There were no statistically significant differences between
      the 2 groups in terms of age and gender. Statistically significant differences in
      metamizole, pethidine, days 3, 5, 6, and 7 visual analogue scale scores were
      observed between the acupuncture and control groups. Postoperative complications
      (atelectasia) were observed in 2 (13.3%) patients, one (6.6%) in each group. The
      postoperative forced expiratory volume in one second/forced vital capacity value
      was higher than the preoperative value in the acupuncture group. CONCLUSIONS:
      Electroacupuncture was more effective than control treatments in decreasing pain
      and limiting opioid and non-opioid medication intake during the first 7
      postoperative days following MS.

PMID- 20677585
TI  - Descriptive epidemiological analysis, MRI signals intensity and histopathological
      correlations of meningiomas.
AB  - OBJECTIVES: To present our experience in operated meningioma cases regarding
      their prevalence, anatomical location, multiplicity, presenting signs and
      symptoms, and the possible correlation between MRI signal intensity and
      histological grades to set criteria for radio-pathological diagnosis. METHODS: In
      this retrospective study, operated meningioma cases in the Department of
      Neurosurgery, Jordan University Hospital (JUH), Amman, Jordan between January
      1997 and January 2007 were reviewed. Our study included 90 cases, and their
      medical records, histopathological reports, and neuroimages were analyzed
      thoroughly. RESULTS: Meningioma was more common in females than males with a
      ratio of 2.2:1. Para-sagittal meningiomas were the most common (23.3%). Multiple
      intracranial meningiomas were found in 4.4% of the cases. Most cases were of
      benign histopathology and exhibited iso-intense signals on T1 and T2, and
      appeared with hyper-intense signals on FLAIR with vivid enhancement. CONCLUSION:
      The prevalence of meningioma among genders and its anatomical location at JUH
      corresponds to the published medical literature worldwide. There was no
      correlation between signal intensities (as seen on T1WI, T2WI, and FLAIR
      sequences), enhancement pattern on one side, and histological grades on the other
      side.

PMID- 20677586
TI  - Effect of systemic parameters following experimental subarachnoid hemorrhage and
      cerebral vasospasm in rabbits by injection of blood into the subarachnoidal
      space.
AB  - OBJECTIVES: To investigate acute changes of systemic parameters following
      experimental subarachnoid hemorrhage (SAH) and cerebral vasospasm conditions
      created by intracisternal injection of fresh autologous blood in a rabbit model.
      METHODS: The study was carried out at the Neurosurgery Clinic, Izmir Training and
      Research Hospital, Izmir, Turkey between April 2002 and March 2005. Thirty-two
      male rabbits were divided into the following 4 groups: group one with mild
      hemorrhage received 0.5 cc of blood, group 2 with moderate hemorrhage received
      0.7 cc of blood, group 3 with severe hemorrhage received 1 cc of blood, and the
      sham-operated group 4 with no blood. The clinical parameters of all animals were
      monitored 2 hours after the operation, and blood analysis was performed just
      after hemorrhage. A series of systemic parameters such as rectal temperature,
      systolic and diastolic blood pressure, and blood gas analysis were measured
      before and after administration of blood injection. Results were compared by
      analysis of variance and paired t-tests, and p-values less than 0.05 were
      considered significant. RESULTS: The systolic blood pressures were significantly
      different in groups 1, 2, and 3 before and after the bleeding period. The
      diastolic blood pressures were also considerably different. CONCLUSIONS: This
      study suggests that the presence of a blood clot and different amounts of blood
      in the subarachnoid space can evoke a series of changes in both local and
      systemic states in experimental models.

PMID- 20677587
TI  - Are left atrial abnormalities a risk for stroke?
AB  - OBJECTIVES: To show that echocardiographic left atrial enlargement (Echo-LAE) and
      electrocardiographic left atrial abnormalities (ECG-LAA) may be probable new risk
      factors for ischemic and hemorrhagic stroke. METHODS: This descriptive
      prospective case study included 140 CT or MRI-confirmed hemorrhagic and ischemic
      stroke patients, who were admitted to Rizgary Teaching Hospital, Erbil, Iraq from
      January 2008 to January 2009. Twelve lead ECG and 2-dimensional transthoracic
      Echo were performed for all patients. Electrocardiographic LAA were identified
      when the P terminal force in lead V1 (PTFV1) was >40 mm.ms. Echocardiographic LAE
      was identified when the left atrial index was more than 2.3 cm/m2. RESULTS:
      Electrocardiographic LAA we resignificantly higher in ischemic stroke patients in
      comparison with the hemorrhagic strokes. Causes of ECG-LAA were found to be as
      follows in order of frequency; hypertension (56%), advanced age (47%), coronary
      artery disease (27%), diabetes mellitus (26%), obesity (21%), valvular heart
      disease (21%), and 2.6% of patients had no identifiable cause. Echocardiographic
      LAE was seen in 34% of ischemic strokes, and 30% of hemorrhagic strokes with no
      significant difference. CONCLUSION: Although ECG-LAA (PTFV1>40 mm.ms) is
      significantly associated with ischemic stroke, it may not be an independent risk
      factor for stroke as it rarely occurred without other risk factors.
      Echocardiographic LAE i s associated with both ischemic and hemorrhagic strokes
      equally.

PMID- 20677588
TI  - Measuring mental health following the 6-year American invasion of Iraq. A general
      health questionnaire analysis of Iraqi medical and dentistry students.
AB  - OBJECTIVES: To explore the current psychological problems among Iraqi medical and
      dentistry students using a General Health Questionnaire after 6 years of armed
      conflicts. METHODS: This study was carried out in the Department of Pharmacology,
      College of Medicine, Al-Mustansiriya University, Baghdad, Iraq from January to
      May 2009. A total of 440 medical and dentistry students were asked to complete
      the 12-item (GHQ-12) and 30-item (GHQ-30) General Health Questionnaire-Arabic
      version to measure the level of their psychological distress. The analysis of
      this cross-sectional study is based on a voluntary self-rating questionnaire
      survey of the assessment of common mental problems. RESULTS: Based on the GHQ-12,
      using simple Likert scoring, probable psychiatric illness (score >12) was
      approximately equal in dentistry (50.6%; 89 out of 176) and medical (51.1%; 135
      out of 264) students, with an odds ratio of 1.138. Based on GHQ-30 using binary
      scoring, the probable cases (score > or = 5) were reported significantly
      (p<0.001) higher in medical students than dentistry students, with an odds ratio
      of 3.251. The means of overall categorized psychiatric morbidity, other than
      social dysfunction, reported in male dentistry students were non-significantly
      higher than corresponding medical students. CONCLUSION: The impact of armed
      conflicts is obvious, therefore, medical and dentistry students need to receive
      effective mental health outreach and treatment, including lifestyle modification,
      at each stage of college life.

PMID- 20677589
TI  - Post-stroke depression and hospital admission. A need for nursing care partition
      according to the clinical condition.
AB  - OBJECTIVES: To investigate the prevalence of post stroke depression and its
      association with hospital admission conditions. METHODS: In this case-control
      study, 120 patients with ischemic cerebral stroke from Aliebne-Abitaleb Hospital,
      Rafsanjan, Iran, during 2004-2006 were evaluated. Sixty patients were
      hospitalized near very ill patients (including patients with delirium, decreased
      consciousness, stupor, coma, sphincteric disorders, ingestion disorder with
      nasogastric tube insertion, and deceased patients) (cases), and 60 were admitted
      not adjacent to ill patients (controls). All patients were matched for stroke
      risk factors and location and size of lesion, and all were admitted to hospital
      for at least one week. Depression was assessed on admission and after one week
      according to the Beck inventory questionnaire. The results were analyzed using
      Fisher's exact test. RESULTS: The mean age of the patients was 63 +/- 4 years,
      and 65% were female. The depression rate in all patients adjacent to ill patients
      significantly increased by the seventh day of admission compared with the control
      group (p<0.001). On analysis according gender, this increase was significant only
      in women (p<0.001). CONCLUSION: Hospitalization of stroke patients without
      considering separation according to clinical condition, increases the depression
      rate in these patients.

PMID- 20677590
TI  - Frontal intraparenchymal schwannoma.
AB  - A 39-year-old female had been subject to headache, and intermittent seizures for
      9 years and decreasing memory for one year, without obvious neurological signs.
      An MRI revealed a 2x2 cm contrast-enhanced lesion in the frontal lobe, with a
      cyst and peritumoral edema, which was not attached to the dura or falx.
      Preoperatively, it was diagnosed as a glioma. Total surgical removal of the
      lesion led to a favorable result. Post-operative histo-pathological examination
      showed characteristic Antoni A and B areas consistent with intraparenchymal
      schwannoma. Intraparenchymal schwannoma is an extremely uncommon lesion, which is
      seen mostly in young adults and children. The main clinical symptoms include
      rising-intracranial-pressure-related manifestations and associated seizure
      disorders. The possible developmental origins, histological, imaging features,
      and protocols of treatment for this entity are discussed.

PMID- 20677591
TI  - Cerebral abscess caused by Aggregatibacter aphrophilus.
AB  - Aggregatibacter aphrophilus was previously known as Haemophilus aphrophilus and
      is a rare cause of disease in humans. A recent reclassification of these
      organisms has placed them in the new genus of Aggregatibacter species. The
      organism seems to be a normal component of oral flora and has been reported to
      cause endocarditis, sinusitis, pneumonia, empyema, soft tissue abscess,
      meningitis, vertebral discitis, and septic arthritis. Brain abscess due to
      Aggregatibacter is rare. We report a case of cerebral abscess due to
      Aggregatibacter aphrophilus and discuss the characteristics of this organism.

PMID- 20677592
TI  - Hypothalamic hamartoma presenting with gelastic seizures, generalized
      convulsions, and ictal psychosis.
AB  - We report a case of hypothalamic hamartoma in an adult female who presented with
      gelastic seizures, generalized convulsions, and ictal aggressive psychotic
      behavior. Anticonvulsant treatment was ineffective in controlling the epileptic
      seizures. Surgical excision after accurate imaging diagnosis 3 decades after the
      onset of symptoms markedly ameliorated her condition. Delayed and erroneous
      diagnosis had unnecessarily prolonged the suffering of our patient.

PMID- 20677593
TI  - Acute disseminated encephalomyelitis associated with enteroviral infection.
AB  - Acute disseminated encephalomyelitis (ADEM) is an acute demyelinating infection
      of the CNS that is characterized by multifocal white matter involvement often
      following an infection and vaccination. A 16-year-old child receiving risperidone
      for 7 years for the treatment of attention-deficit/hyperactivity disorder was
      hospitalized with complaints of double-vision during the past month and weakness
      on his right side, ataxia, and vomiting over the past 3 days. The child was
      diagnosed with ADEM after clinical, laboratory, and cranial MRI was conducted.
      Following an initial 3-day therapy with pulsed methylprednisolone, the child
      showed obvious clinical improvement. The treatment was continued with
      prednisolone and significant improvement was achieved. Enterovirus was detected
      in the results of the viral examination of the CSF. This child was found to be an
      interesting case having been diagnosed with ADEM associated with enteroviral
      infection, because of the rarity of few case reports in the literature.

PMID- 20677594
TI  - An unusual descending aortic dissection with dramatic neurologic presentation.

PMID- 20677595
TI  - The importance of the clinical examination.

PMID- 20677596
TI  - Brain abscess due to Haemophilus aphrophilus.

PMID- 20677597
TI  - Dandy Walker malformation and hypertrophic cardiomyopathy. Unusual fatal
      association.

PMID- 20677598
TI  - Amyotrophic lateral sclerosis. Is it a sequela of surgical intervention?

PMID- 20677599
TI  - Multiple sclerosis.

PMID- 20677600
TI  - Opportunistic infections in relation to CD4 level among HIV seropositive patients
      from central Nepal.
AB  - CD4 cells status of HIV patients provides one of the benchmarks against the
      progression of HIV/AIDS. Regular investigation of opportunistic infection in HIV
      patients is one of the major components of HIV/AIDS care and support service.
      Between October 2007 and May 2008, a cross-sectional analytical study was carried
      out in Tribhuvan University Teaching Hospital with an objective to find the
      relationship between CD4 level and opportunistic infections. After taking
      informed consent pre-structured questionnaire was filled and specimens were
      collected to investigate major opportunistic infections (OIs) as per standard
      microbiological procedure. All the information were entered into SPSS 11.5 system
      and analyzed. Of the 150 patients, 100 (66.7%) were males and 50 (33.3%) were
      females. The age group 21-30 years was predominant (42.7%) followed by 31-40
      years (42%). Oral candidiasis was found to be the predominant OIs (32.0%)
      followed by streptococcal pneumonia (28.7%), Salmonella infection (20.7%),
      cryptosporidial infection (19.3%) and tuberculosis (10.0%). Significant
      relationship could be established between low CD4 count (<200) and the appearance
      of oral candidiasis (/2=9.16, p<0.05) but no such relationship could be
      established regarding other OIs. So, it can be concluded that appearance of oral
      candidiasis is the strong evidence of advanced stage of HIV infection.

PMID- 20677601
TI  - Twenty four hours urine and serum biochemical parameters in patients with
      urolithiasis.
AB  - From the analysis of various urinary constituents and the estimation of serum
      parameters, it is now possible to identify the risk factors responsible for or
      contributing for stone formation metabolic factor included calcium, oxalate, uric
      acid, citrate and pH. Environmental factors where total volume, sodium, phosphate
      and magnesium. Urinary citrate and magnesium found to be lower in stone formers.
      The levels of serum parameters like calcium, sodium and intact parathyroid
      hormone (IPTH) is higher than normal. Where as potassium and magnesium is found
      to be lower than normal. Higher level of IPTH is associated with primary
      hyperparathyroidism and is related with stone formation in-patient with
      urolithiasis. Serum levels of phosphorus, uric acid and Creatinine found to be
      normal.

PMID- 20677602
TI  - A clinical study on the management of generalized anxiety disorder with Centella
      asiatica.
AB  - Centella asiatica is reputed for its beneficial effects in various neurological
      disorders. The present investigation was undertaken to evaluate the role of 70%
      hydro-ethanolic extract of Centella asiatica (CA) on generalized anxiety disorder
      (GAD) in man. Hamilton's Brief Psychiatric Rating Scale (BPRS) was used to screen
      the subjects. Thirty-three participants (18 male and 15 female; average age 33
      yrs) were medicated with the CA in a fixed dose regime (500 mg/capsule, twice
      daily, after meal). They were thoroughly investigated using standard
      questionnaires based on psychological rating scale at baseline (day 0), mid-term
      (day 30) and final (day 60). The scale also includes a number of direct queries
      about current levels of experienced stress. The observations revealed that, CA
      not only significantly (p<0.01) attenuated anxiety related disorders but it also
      significantly (p<0.01) reduced stress phenomenon and its correlated depression.
      CA further significantly (p<0.01) improved the willingness for adjustment and
      cognition. Results indicated that Centella asiatica may be useful in the
      treatment of GAD and may be used as a promising anxiolytic agent in near future.

PMID- 20677603
TI  - Control of coliform bacteria detected from diarrhea associated patients by
      extracts of Moringa oleifera.
AB  - The aims of this study were to determine the total population of coliform
      bacteria in the samples collected from diarrhea associated patients from the
      local area of Bangladesh and to examine the antibacterial efficacy of leaf
      extracts of Moringa oleifera (Moringaceae) against the isolated coliform
      bacteria. The coliform bacteria detected in these samples by some microbial
      biochemical tests such as Escherichia coli, Shigella dysenteriae, Salmonella sp.,
      Enterobacter sp., Klebsiella pneumoniae and Serratia marcescens. The total
      isolation rate of coliform bacterial species was ranged from 38.01-3.51%. At the
      concentration of 300 ig/disc, the organic extracts of hexane, chloroform, ethyl
      acetate and methanol extracts of Moringa oleifera leaf exhibited a remarkable
      antibacterial effect against all the tested bacterial pathogens. The zones of
      inhibition against all the tested bacterial pathogens were found in the range of
      8.0 to 23.2 mm, along with their respective minimum inhibitory concentration
      (MIC) values ranging from 62.5-1000 ig/mL. The results obtained in this study
      suggest that the extracts from Moringa oleifera leaf can be a source of natural
      antimicrobials with potential applications in pharmaceutical industry to control
      coliform bacteria.

PMID- 20677604
TI  - Deep-seated thoracic and abdominal lesions: usefulness of ultrasound guided fine
      needle aspiration cytology, a 3 year experience.
AB  - Three hundred twenty patients were subjected to ultrasound guided fine needle
      aspiration cytology (FNAC) over a 3 year period (April 2006 - March 2009). These
      included liver (125 cases), lung (81 cases), abdominal and mediastinal lymph
      nodes (29 cases), ovary (14 cases), omentum (12 cases), pancreas (10 cases),
      kidney (10 cases), mediastinum (8 cases), gall bladder (8 cases) etc. The aim of
      this study was to evaluate the overall utility of ultrasonographic guided FNAC in
      the diagnosis of abdominal and thoracic lesions. In 264 cases (82.5%), FNAC was
      diagnostic with commonest diagnosis being malignant neoplasm (70.0%). 14 cases
      (4.4%) were suspicious of malignancy and remaining 42 (13.1%) cases either didn't
      reveal diagnostic material or they were inconclusive. In liver, Metastatic
      adenocarcinoma is the commonest tumor, while in lung; the commonest lesion is non
      small cell carcinoma. Benign neoplasm (3.1%) and non neoplastic lesion (9.4%)
      were also diagnosed by FNAC. Rare sites like oesophagus and duodenum were also
      aspirated. Complication rate was too low (0.9%) in this study. USG guided FNAC,
      in conjunction with clinico-radiological parameters are accurate and safe in
      diagnosing deep-seated mass lesions in the thorax and abdomen.

PMID- 20677605
TI  - Nasal carriage rate of methicillin resistant Staphylococcus aureus among at
      National Medical College Teaching Hospital, Birgunj, Nepal.
AB  - Present study was conducted to assess the nasal carriage rate of methicilin
      resistant Staphylococcus aureus (MRSA) among patients, visitors/patient
      attendants and healthcare personnel at National Medical College Teaching
      Hospital, Birgunj, Nepal. A total of 112 nasal swabs (patients: 31,
      visitors/patient attendants: 61, and healthcare personnel: 20) were subjected to
      bacteriological investigation following standard protocol. S. aureus isolates
      were identified by mannitol fermentation and coagulase positivity. Antimicrobial
      susceptibility test was performed by Kirby-Bauer's disc diffusion method on
      Muller-Hinton agar medium. S. aureus was isolated in 14 (12.5%) of participants
      (M: 11.3%, F: 13.6%). Highest nasal colonization rate was found among healthcare
      personnel (25.0%) followed by the visitors/patient attendants (13.1%) and the
      patients (3.2%) (P>0.05). Highest positive rate was observed in the age group
      d"14 years (33.3%), followed by 15 to 50 years (13.2%) and >50 years (5.6%)
      (P>0.05). Out of 14 S. aureus isolates, 57.1% were methicillin resistant,
      prevalence rate of MRSA among total subjects being 7.1%. MRSA prevalence rate
      were 5.6% and 8.5% in total male and female participants, respectively (P>0.05).
      Highest MRSA prevalence rate was among health-care personnel (10.0%), followed by
      visitors/patient attendants (8.2%) and the patients (3.2%) (P>0.05). All MRSA
      isolates were resistant to Ampicillin, followed by Cephalexin (37.5%),
      Ciprofloxacin (37.5%), Tetracycline (37.5%), Gentamycin (25.0%), Erythromycin
      (0.0%) and Vancomycin (0.0%). High rate of nasal MRSA carriage rate found in this
      study indicates the need for standard infection control to prevent MRSA
      transmission.

PMID- 20677606
TI  - Spinal anesthesia for cesarean section: comparison of 5.0% lignocaine and 0.5%
      bupivacaine.
AB  - Objective of the study was to compare the effect of the drugs, intraoperative
      hemodynamic variables (heart rate, blood pressure) and associated complications
      (hypotension, nausea, shivering etc) between the bupivacaine and lignocaine
      group, when administered intrathecally in patients undergoing caesarean section.
      This is a randomized prospective study where the haemodynamic changes and the
      complications following sub arachnoid block either with 5.0% lignocaine or with
      0.5% bupivacaine in 52 patients undergoing caeserian section were compared. The
      patients were randomly divided in two groups, group X (lignocaine group, n=26) or
      group B (bupivacaine group, n=26), either to receive 5.0% lignocaine 75 mg or
      0.5% bupivacaine 12.5 mg. Intraoperatively heart rate, blood pressure (systolic
      (SBP), diastolic (DBP) and mean (MAP)), oxygen saturation were monitored. Any
      rescue drugs e.g. mephentermine, crystalloid 200 ml bolus, pethidine, diazepam
      etc given were noted with the dose and time. Urine output and total amount of
      fluid given was noted at the end of the surgery. Oxytocin 10 U in infusion was
      given after the baby was delivered in all the cases. Intraoperative blood
      pressures, total amount of fluid given, rescue vasopressor (mephentermine) given
      were compared in both the groups. Groups were also compared with respect to the
      patients' age, height of sensory block, motor block, duration of surgery, Apgar
      score and weight of the baby and duration of postoperative analgesia. It was
      concluded that the drugs were similar with respect to their sensory and motor
      effects, intraoperative hemodynamic changes like hypotension and bradycardia, and
      other complications like shivering and can be used interchangeably as spinal
      anesthetic agent for caesarean section deliveries.

PMID- 20677607
TI  - Study of fibrinogen in patients with diabetes mellitus.
AB  - Patients with diabetes mellitus have 2 to 4 times increased risk for
      cardiovascular disease than non-diabetic patients. However this excess risk is
      not fully explained by the traditional cardiovascular risk factors (Hypertension,
      Hypercholesterolaemia, Smoking and Obesity) which are also associated with
      diabetes. Fibrinogen has been identified as an independent risk factor for
      cardiovascular disease and it is associated with traditional cardiovascular risk
      factors. This is a descriptive analytical cross-sectional study carried out in
      Tribhuvan University Teaching Hospital (TUTH) medical outpatient department and
      Medical ward from June 2005 to June 2006. A total of 120 consecutive patients
      were enrolled; 30 patients having Diabetes. Next 30 patients having both diabetes
      and coronary artery disease. Thirty patients having only coronary artery disease
      but no diabetes. And 30 patients (control) not having both diabetes and coronary
      artery disease. Fibrinogen was found to be significantly higher in patients with
      diabetes than control. Fibrinogen was significantly higher in diabetic patients
      with coronary artery disease than those patients who had only diabetes or
      coronary artery disease (p value<0.01).

PMID- 20677608
TI  - Removal of coin from upper esophageal tract in children with Magill's forceps
      under propofol sedation.
AB  - Foreign body ingestion is a common emergency problem in children. Coins are the
      most common foreign bodies lodged in the esophagus. This is a retrospective study
      where we reviewed 21 consecutive paediatric cases of coins impacted in the upper
      esophagus. These children were attended at the BP Koirala Institute of Health
      Sciences, Dharan, from March 2007 to March 2008. In this study, Mc-Intosh
      laryngoscopes were inserted into the pharynx to elevate the larynx and to expose
      the esophageal entrance. Then Magill's forceps were advanced into the esophagus
      and opened in order to see and extract the coin from the esophagus under propofol
      sedation. Coins were successfully removed by Magill forceps without any
      complications from all 21 children. Amongst these children, 14 (66.7%) were male
      and 7 (33.3%) were female. The mean age of the children was 3.79 (+/- 3.02)
      years. The coin was grasped and extracted on the first attempt in all 21
      patients. The mean time for the removal of the coin (i.e. initiation of
      laryngoscope to removal of coin) was 51.48 (+/- 24.17) seconds. During direct
      laryngoscopy, 15 (71.4%) coins were visualized clearly, whereas 6 (28.6%) were
      not. However all coins were successfully removed. The most commonly ingested coin
      is a one rupee Nepali coin (42.9%) followed by a two rupee coin (19.0%) and an
      Indian one rupee coin. Thus it can be seen that the coin impacted at the
      cricopharynx and upper oesophagus can be safely, easily and quickly removed by
      direct laryngoscopy and Magill's forceps under propofol sedation.

PMID- 20677609
TI  - Health problems and social consequences in teenage pregnancy in rural Kathmandu
      Valley.
AB  - Early marriage, less awareness of family life education, low socio economic
      condition and burden of large families in rural area are the contributory factors
      to high teenage pregnancy and its complications. A rural health centre based
      cross sectionals study was under taken over six month period among teenage (10-19
      years) in the rural Kathmandu Valley. The study sample comprises (15-19 years
      old) 180 subjects. Data includes demographical variables as anemia, preterm
      delivery, abortion and hemoglobin. Preterm delivery cases within 37 weeks of
      gestation. Below 10 gm. of Hb was considered as anemia. The prevalence of anemia
      was quite high (56.66%) in teenage pregnancy. However severe (<7.9 gm) anemia was
      observed in 55.67% cases.

PMID- 20677610
TI  - Spirometric evaluation of pulmonary function tests in clinically diagnosed
      patients of bronchial asthma.
AB  - The present study was undertaken to assess the difference between the normal
      predicted value and observed value of pulmonary function test (PFT) amongst the
      asthmatic patients and also to compare the aforesaid observed values between male
      and female asthmatic patients. Clinically diagnosed cases (male 62, female 75) of
      bronchial asthma attending medical out patient department of Nepal Medical
      College Teaching Hospital were assessed. All the pulmonary parameters showed
      significantly less observed values than the normal predicted values except PEFR
      in female and FVC in male asthmatic patients. Hence, PEFR in female and FVC in
      male asthmatic patients might not be considered as a valid parameter to indicate
      bronchial asthma. Present study also revealed that all the pulmonary variables
      were significantly higher in males than in females.

PMID- 20677611
TI  - The incidence of color blindness among some school children of Pokhara, Western
      Nepal.
AB  - The incidence of color blindness varies from race to race and different in
      different geographical area. Since, there is no such report about the prevalence
      of color blindness in the western part of Nepal, the present study had been
      conducted to find out the incidence of color blindness among school children of
      Pokhara city, western Nepal. Participant's (n=964, 474 boys, 490 girls, age group
      10 to 19 years) color vision was tested by using Ishihara chart (38 plates).
      Among 474 boys, 18 boys were color blind with the prevalence of 3.8%. None of
      girls were found to be color blind. Out of 18 color blind boys, nine, six and
      three boys were the victims of deuteranopia, deuteranomaly and protanomaly
      respectively. The incidence of color blindness were more amongst the Darji
      (14.3%) and Newar (9.1%) ethnic groups.

PMID- 20677612
TI  - Isolated appendicular tuberculosis (TB) presented as peritonitis.
AB  - Tuberculosis is very common entity in both developing and under developed
      countries. Each year 3 million people worldwide died of the disease. Among extra
      pulmonary TB, alimentary system accounts for about 3.0% cases. The Commonest
      presentation of alimentary tuberculosis is Ileo-caecal disease, but isolated
      appendicular involvement is very rarely seen. Although some cases have been
      reported from our neighboring countries, there is still no such report from
      Bangladesh. We are here for the first time reporting a case of isolated
      appendicular tuberculosis which presented to us with peritonitis.

PMID- 20677613
TI  - "Safety pin"--a question to its safety!
AB  - Foreign body ingestion is not an uncommon problem in children. They can ingest
      various foreign objects and one of such objects is a safety pin. The ingestion of
      such foreign body is not widely reported in the literature. This case highlights
      the risk of accidental ingestion of safety pin used on child's clothing to
      protect him from cold that can result in lethal complications. In a poor
      developing country like Nepal, this case serves to address all mothers alerting
      them of their ignorance while using safety pin in infants. In addition,
      physicians are reminded to obtain a detailed inquiry of suspected foreign body
      ingestion in every child with the history of dysphagia.

PMID- 20677614
TI  - Mucinous cystic neoplasm masquerading a pseudo pancreatic cyst.
AB  - Owing to recent improvements in pancreatic imaging, an increasing number of
      cystic lesions have been identified in asymptomatic as well as in patients
      presenting with jaundice, pancreatitis, or abdominal pain. In spite of many
      diagnostic modalities, pseudocysts of pancreas still create confusions with
      pancreatic cystic neoplasms. Here we report a 38 year old lady who presented with
      abdominal lump and jaundice following an episode of pain abdomen suggesting acute
      pancreatitis. She was fully investigated and managed for pseudocyst of pancreas.
      The diagnosis of mucinous cystic neoplasm was evident only after the biopsy from
      the wall of the cyst.

PMID- 20677615
TI  - Penetrating neck injury by an arrow: a paradigm of age old assault.
AB  - Penetrating neck injuries by traditional weapons are rare entity in the modern
      era of sophisticated weapons. We report an unusual case of penetrating neck
      injury by a metallic arrow entering anterior neck in zone II and its tip coming
      out of neck posteriorly causing difficulty for patient to lie down as well as
      posing challenge to intubate. Arrows are low velocity projectile and from a close
      proximity they can cause penetrating trauma similar to a low powered handgun.
      Management of the case was discussed.

PMID- 20677616
TI  - High lipemic serum: a case report.
AB  - Hypertriglyceridemia is the condition in which the triglyceride level in the
      blood is elevated. Triglycerides (TGs) are the major source of energy stored in
      the body. In this case a 66 years old gentleman has consumed pork with alcohol. A
      milky white serum was observed due to high triglyceride level. However, he had no
      other lipid disorders. The increased triglyceride level was purely of dietary
      origin last night. The subject was perfectly fine with lipid profile and other
      biochemical investigations performed one week later.

PMID- 20677617
TI  - [Consensus guidelines for diagnosis, treatment and follow-up of patients with
      pancreatic neuroendocrine tumors].
AB  - Pancreatic neuroendocrine tumors (PETs) are increasingly recognized. In order to
      assure an optimal treatment of patients and to propose an efficient diagnostic
      algorithm we were prompted to organize meetings, with participating experts,
      specialists in different fields of expertise. The idea for the meetings was to
      try to give a standardized approach, which would in future help in stratification
      of PET patients. Results of meetings are given in a form of Consensus guidelines
      for diagnosis, treatment and follow-up of patients with pancreatic neuroendocrine
      tumors.

PMID- 20677618
TI  - [Reimbursement of generics in Croatia: should more have been done?].
AB  - BACKGROUND: while numerous ordinances on drug pricing and reimbursement have been
      enacted, trying to suppress the drug expenditure in Croatia, it seemed there were
      inconsistencies in pricing procedures of some of the drugs. OBJECTIVES: to show
      whether or not the pricing system given has had the desired result, we review
      pricing and reimbursement systems of generics in some of the EU countries and
      give suggestions for even more effective pricing and reimbursement system in
      Croatia. DATA AND METHOD: IMS Sales Data for the years 2004 to 2007 were used to
      show the differences between desired and real price levels of generics within the
      control group. RESULTS: detailed analysis of the observed group of drugs showed
      that inappropriately priced drugs accounted for 100% in the year 2004 and fell to
      60% of total expenditure within the observed group in the year 2007. The
      reference pricing system should be enacted, free price setting and financial
      incentives for physicians and pharmacists, as well as private insurance packages
      for non-reimbursed service or drugs or co-payments.

PMID- 20677619
TI  - [The influence of "hygienic minimum" course on quality of catering
      establishments].
AB  - The aim of this article was to define the quality of catering establishments in
      Virovitica Podravina county before and after the course of "hygienic minimum".
      Research was realized through interview and assessment of microbiological swabs
      of the same catering establishments before and after the course of "hygienic
      minimum". All procedures were performed according to Regulations on standard
      specification in microbiological cleanness and methods of its determining. Twenty
      five catering establishments from a group of restaurants and bars were analyzed.
      In all of them we found improvement in the most of examined parameters. So,
      implementation of the course through the existing program has proven to be
      justified.

PMID- 20677620
TI  - [Tolosa-Hunt syndrome: a case report].
AB  - Tolosa-Hunt syndrome is a nonspecific granulomatous inflammation of the cavernous
      sinus, superior orbital fissure and apex of the orbit. It involves episodes of
      unilateral orbital pain which may last several weeks, lesions of cranial nerve
      III, IV or VI, and rarely II, V, VII and VIII. It is characterized by remissions
      and exacerbations, and can cause permanent neurological disorder of the affected
      nerves. We present the course of the disease in a patient whose initial symptom
      was gradual visual loss in the right eye, followed by neuralgic pain in the right
      orbit and face. The diagnosis was confirmed by biopsy and corticosteroid therapy
      was administered. Exacerbation of the disease required repeated surgery, excision
      of the fibrous tissue of the cavernous sinus, as well as prolonged corticosteroid
      therapy.

PMID- 20677621
TI  - [Reversible posterior leukoencephalopathy or brain tumor--case report].
AB  - Reversible posterior leukoencephalopathy (RPLE) syndrome is clinically associated
      with headache, altered consciousness, seizures and visual symptoms. On brain
      magnetic resonance imaging (MRI) there is edema predominantly affecting white
      matter of the parietooccipital brain regions. Initially, this syndrome was
      believed to be secondary to hypertension, renal disease, or immunosuppressive
      therapy. However, it has recently been identified in a wide variety of
      conditions, including eclampsia, hemolytic-uremic syndrome, connective tissue
      diseases, malignancies, etc. Authors describe a case of a 72-year-old woman with
      a history of arterial hypertension, who suddenly developed headache, confusion,
      left homonymous hemianopsia, and left hemiparesis, associated with high blood
      pressure. Brain MRI revealed extensive white matter lesion in the right parietal
      and occipital lobe, splenium corpus callosum and left occipital lobe, suggestive
      of expansive process. However, after extensive diagnostic work-up, diagnosis of
      reversible posterior leukoencephalopathy was established, connected with arterial
      hypertension. At the moment the patient is without neurological symptoms, follow
      up brain MRI revealed resolution of white matter lesion.

PMID- 20677622
TI  - [Pathohistological diagnosis of prostatic carcinoma in needle core biopsies].
AB  - Prostate cancer is the most common visceral tumor in males. It is the second most
      common cause of death in males due to malignant tumors. It usually appears in
      persons older than 50 years. It can be detected in asymptomatic patients by a
      simple and easily accessible procedure that includes prostate specific antigen
      measurement and needle core biopsy. Such an approach enables adequate treatment,
      insures better prognosis and even cures the patients. We describe the needle core
      biopsy approach and its potential in the early pathohistological diagnosis of
      prostate cancer. We also describe the most common histological types of prostate
      carcinoma as well as various nontumorous mimickers which should be considered in
      the differential diagnosis, in order to avoid false positive diagnosis and
      unnecessary prostatectomies.

PMID- 20677623
TI  - [Systemic sclerosis--pathogenesis, clinical manifestations and treatment].
AB  - Diffuse systemic sclerosis (SSc) is a chronic disease of unknown cause
      characterized by diffuse fibrosis and vascular abnormalities in the skin and
      internal organs. Pathogenesis of SSc involves immunologic mechanisms, vascular
      damage and activation of fibroblasts. SSc varies in severity and progression;
      most patients eventually develop visceral complications, which are the usual
      causes of death. No drug significantly influences the natural history of SSc
      overall, but various drugs are of value in treating specific symptoms or organ
      systems. This review discusses pathogenesis, clinical manifestations and possible
      treatment of SSc.

PMID- 20677624
TI  - [The treatment of asthma exacerbations in adults].
AB  - Asthma exacerbation is characterized by a rapid and progressive worsening of
      symptoms, mainly dyspnea, cough, wheezing and chest tightness. The intensity of
      an exacerbation may vary form a mild, transient worsening marked by a cough and
      moderate shortness of breath to a very severe and life-threatening condition. The
      clinical features of asthma include increased rate of breathing, cough, and
      prolonged and difficult expiration. The expiratory flow limitation could be
      quantified, objectified, and monitored by the lung function measurements (PEF or
      FEV1 ). It is of crucial importance to recognize properly the early signs of an
      exacerbation, judge its severity, and promptly start the treatments. The strategy
      of the treatment of an asthma exacerbation includes the repeated administration
      of rapid-acting inhaled bronchodilators, the early introduction of systemic
      glucocorticoids and oxygen supplementation. The treatment is aimed to resolve the
      airflow limitation and ameliorate the hypoxemia, as quickly as possible. Mild
      exacerbations could be treated in general practice while the severe ones should
      be treated in emergence units.

PMID- 20677625
TI  - [Exercise-induced anaphylaxis--a review].
AB  - Exercise-induced anaphylaxis (EIA) is a syndrome in which patients experience the
      symptoms of anaphylaxis, which occur only after increased physical activity. It
      is characterised by a gradual development of symptoms: itching, erythema,
      urticaria, angioedema, anaphylactic shock (hypotension, syncope, loss of
      consciousness, shortness of breath, wheezing, nausea and vomiting), and at the
      end of the late phase prolonged urticaria and headache. The triggering factors
      for EIA are as follows: significant exposure to airborne allergens, insect sting,
      weather extremes, higher air humidity, taking nonsteroidal anti-inflammatory
      drugs. The most frequent causative nutritive allergens include wheat, crabs and
      shells. Prophylactic management for EIA comprises avoding the triggers. Exercise
      or other physical activity should be performed in proximity of medically trained
      companion.

PMID- 20677626
TI  - [Eminent medical doctor from Karlovac Dr. Milan Nemicic (1884-1930)].
AB  - Milan Nemicic was born in 1844 in Petrinja, Croatia. He was promoted as medical
      doctor at Vienna medical school (Jozefinum) in 1868. In 1873 he became chief
      medical officer in regiment. During occupation of Bosnia and Herzegovina in 1878
      he was very active in war operations near Bihad. In 1883 he was elected city
      physician in Karlovac and head doctor in Karlovac city hospital. During 1886 he
      was in Pasteur Institute in Paris and together with Louis Pasteur studied
      vaccination process in rabies. His results were published in Liecnicki vjestnik.
      He undertook first biological experiment on rabbit with rabies in Croatia, and he
      was first to have vaccinated patients with Pasteur's antirabies vaccine. Lexicon
      medicorum (Ljekarski rjecnik) was his biggest accomplishment printed in Zagreb
      1898. He was retired in 1904 and lived in Graz, last years of his life he spent
      in Merano and died in 1930 at the age of 86 years.

PMID- 20677627
TI  - [The introduction of sugammadex into the clinical practice in Croatia--the role
      of succinylcholine re-visited].

PMID- 20677628
TI  - [To promote the clinical application of endobronchial ultrasound-guided
      transbronchial needle aspiration in China].

PMID- 20677629
TI  - [Recent developments and perspectives of endobronchial ultrasound in thoracic
      tumor].

PMID- 20677630
TI  - [The role of TBNA in diagnosis and treatment of lung diseases].
AB  - In the last 30 years, clinical application oftransbronchial needle aspiration
      (TBNA) has proved its efficiency, accuracy, safety and cost-effectiveness,
      particularly in diagnosing and staging lung cancer as well as in diagnosing
      benign diseases. The application of endobronchial ultrasound (EBUS) increased the
      accuracy of TBNA. Endobronchial ultrasound guided transbronchial needle
      aspiration (EBUS-TBNA) has superior performance and allowing real-time sampling
      under direct vision. Combination of EUBS-TBNA and traditional methods (CT, PET,
      mediastinoscopy, et al) can improve the diagnostic rate and negative predictive
      value. In the future, EUBS-TBNA may have applications in both benign and
      malignant lung diseases as a routine examination.

PMID- 20677631
TI  - [Role of EBUS-TBNA for mediastinal lymph node staging of lung cancer].

PMID- 20677632
TI  - [Endobronchial ultrasound-guided transbronchial needle aspiration for mediastinal
      staging of lung cancer and diagnosis of intrathoracic lesions].

PMID- 20677633
TI  - [Application of real time endobronchial ultrasound-guided transbronchial needle
      aspiration for lung cancer staging].

PMID- 20677634
TI  - [Review of the role of EBUS-TBNA for the pulmonologist, including lung cancer
      staging].

PMID- 20677635
TI  - [Endobronchial ultrasound-guided tranbronchial needle aspiration (EBUS-TBNA) in
      the diagnosis and staging of lung cancer].

PMID- 20677636
TI  - [Pathological basis of air bronchogram examined by endobronchial ultrasound in
      patients with peripheral lung cancer].
AB  - BACKGROUND AND OBJECTIVE: Air bronchogram were visible in endobronchial
      ultrasound images of benign and malignant lesions. The aim of this study is to
      analyze the endobronchial ultrasound images of different characteristics of air
      bronchogram and clinical significance combined with pathologic section. METHODS:
      From June 1, 2005 to December 30, 2008, 92 patients were found pulmonary
      peripheral lesions by X-ray and CT examinations, and confirmed that lesions were
      located lower to the segmental bronchial orifice by flexible bronchoscopy
      examinations. These patients were examined by radial endobronchial ultrasound
      probe afterwards. RESULTS: Seventy-eight patients clarified with benign or
      malignant diagnosis of lesions were analyzed, among whom, 22 of 47 (46.8%) were
      of malignant lesion without air bronchogram, 22 patients in 25 of lesions without
      air bronchogram were confirmed malignant (88%), among whom, 66.7% (2/3), were of
      small cell lung cancer, 43.9% (18/41) were of non-small cell lung cancer, and 50%
      (5/10) were of poorly differentiated adenocarcinoma, no sign of air bronchogram
      was found in corresponding pathological sections. Among those patients with
      malignant lesion, 51.1% (24/47) were of irregular air bronchogram. For patients
      with malignant lesions, irregular air bronchogram was most commonly found in
      adenocarcinoma, 55.2% (16/29) of pathological sections showed signs of air
      bronchogram, similar sign was also found in 2 patients with moderately
      differentiated adenocarcinoma and 1 patient with poorly differentiated
      adenocarcinoma. The total percentage of patients without air bronchogram and with
      irregular air bronchogram was 97.9% (46/47), only one of them (with medium
      differentiated adenocarcinoma) showed regular air bronchogram (1.3%). 80.6%
      (25/31) patients with benign lesion showed regular sign of air bronchogram
      distributed in the shape of concentric circles, the percentage of patients
      without air bronchogram or with irregular air bronchogram was both 3.8% (3/31).
      CONCLUSION: When there's no air bronchogram, or irregular air bronchogram sign
      found by endobronchial ultrasound examination, it is highly indicated that there
      is a malignant lesion, while there's regular sign of air bronchogram distributed
      in the shape of concentric circles, it is likely to be a benign lesion.

PMID- 20677637
TI  - [Role of endobronchial ultrasound-guided transbronchial needle aspiration in the
      diagnosis of bronchogenic carcinoma].
AB  - BACKGROUND AND OBJECTIVE: The aim of this study is to evaluate diagnostic yield
      and the safety of endobronchial ultrasound-guided transbronchial needle
      aspiration (EBUS-TBNA) in the diagnosis ofbronchogenic carcinoma. METHODS:
      Between July, 2009 and February, 2010, 95 patients with mediastinal/hilar
      lymphadenopathy and/or intrathoracic peritracheal or peribronchial masses
      previously detected with CT scan underwent EBUS-TBNA. No rapid onsite cytology
      was performed. RESULTS: In all 95 patients, 60 cases were newly diagnosed lung
      cancer through the pathological examination and clinical follow-up certification.
      In 60 lung cancer cases, 112 samples were obtained from lymph nodes (LNs) and 11
      samples were obtained from intrapulmonary lesions. Fifty-eight cases of patients
      were diagnosed, false negative in 2 cases. Sensitivity and specificity of EBUS
      guided TBNA method in distinguishing benign from malignant LNs or thoracic masses
      were 96.67% and 100%, respectively. There was any major complication in this
      series, the procedure was uneventful. CONCLUSION: EBUSTBNA seemed a safe and
      effective technique in making bronchogenic carcinoma diagnosis for
      mediastinal/hilar LNs and intra-pulmonary masses.

PMID- 20677638
TI  - [Initial experience on endobronchial ultrasound-guided transbronchial needle
      aspiration in the diagnosis and staging of lung cancer].
AB  - BACKGROUND AND OBJECTIVE: It has been proven that endobronchial ultrasound-guided
      transbronchial needle aspiration (EBUS-TBNA) was a new minimally invasive method
      in the diagnosis for mediastinal lymph nodes. The aim of this study is to
      evaluate the diagnostic and staging yield of EBUS-TBNA for lung cancer. METHODS:
      Seventy-five patients with tumors and enlarged mediastinal lymph nodes found by
      CT underwent the diagnosis by endobronchial ultrasound-guided transbronchial
      needle aspiration (EBUS-TBNA) from April 1, 2009 to Febuary 8, 2010. The
      sensitivity, specificity, positive predictive value, negative predictive value
      and diagnostic accuracy of EBUS-TBNA were evaluated. RESULTS: Seventy-five
      patients with 177 lymph node groups (2.4 groups in average) were studied.
      Histopathological samples were found in 49.33% patients and in 28.81% groups.
      Overall sensitivity, specificity, positive predictive value, negative predictive
      value and diagnostic accuracy of EBUS-TBNA for diagnostic were 98.43%, 100.00%,
      100.00%, 91.67% and 98.66%, respectively, in per patient analysis and were
      95.10%, 100%, 100.00%, 82.93%, and 96.05%, respectively, in per group analysis,
      higher than CT examination (P < 0.05) expect for sensitivity (P = 0.435). Staging
      changed in 19 (26.03%) patients after EBUS-TBNA. CONCLUSION: EBUS-TBNA proved to
      be a safe procedure with a high yield for the diagnosis of lung cancer.

PMID- 20677639
TI  - [Morphology and edge analysis of endobronchial ultrasound images in 47 patients
      with pulmonary malignant lesions].
AB  - BACKGROUND AND OBJECTIVE: By analyzing morpholoy and edge of endobronchial
      ultrasound (EBUS) images in 47 patients with pulmonary malignant lesions. The aim
      of this study is to explore the role of EBUS in the diagnosis of pulmonary
      malignant lesions. METHODS: From June 1, 2005 to June 30, 2006, EBUS analysis was
      performed in a proportion of patients with malignant or benign lesions. RESULTS:
      In total 78 patients of confirmed diagnosis, 47 cases were confirmed malignant
      lesions, and 31 were benign lesions, male 56 cases, female 22 cases, age span
      from 21-80 years (58.01 +/- 13.20). The statistics of the lesion edge imaging in
      78 patients showed that different position and angle did not affect the morphous
      of the edge; analysis of the relationship between the size of the lesion and the
      morphous of the edge shows that the size of the lesion does not affect the
      morphous of the edge; the comparison between lesions of benign and malignant
      shows that a clear edge is the major feature of malignant lesions, indicating
      certain value in diagnosis; comparison between the shape of the lesion and the
      property of the lesion shows no relationship between them; compared to
      conventional bronchoscopy operations, the EBUS operation consumes approximately
      10 min, and no related complication was found. CONCLUSION: Clear morphous of the
      edge in EBUS is a feature of the malignant lesion, and EBUS has certain value in
      the diagnosis of the malignant lesions.

PMID- 20677640
TI  - [Diagnostic value of transbronchial needle aspiration and endobronchial
      ultrasound-guided transbronchial needle aspiration for hilar and mediastinal
      lymph nodes in lung cancer patients].
AB  - BACKGROUND AND OBJECTIVE: Transbronchial needle aspiration (TBNA) and
      endobronchial ultrasound-guided TBNA (EBUS-TBNA) have been applied to the
      diagnosis for mediastinal lymph nodes. The aim of this study is to evaluate the
      clinical value and safety of TBNA and EBUS-TBNA on hilar and mediastinal lymph
      nodes of lung cancer patients. METHODS: Two hundred fifty patients with suspected
      lung cancer were enrolled. All petients with hilar and/or m lymphoadenopa
      ediastinal thy found by CT scan received TBNA, biopsy and brushing. EBUS-TBNA was
      performed in 15 patients among them. RESULTS: Lung cancer were confirmed in 180
      patients by TBNA, biopsy and brushing. The positive rates were 82.86%, 51.24% and
      45.45%. Fifteen patients after EBUS-TBNA had a positive rate of 91.67%.
      CONCLUSION: TBNA and EBUS-TBNA were proved to be safe procedure with a high yield
      for the diagnosis ofhilar and mediastinal lymph nodes in lung cancer patients.

PMID- 20677641
TI  - [Defective expression of TGFBR3 gene and its molecular mechanisms in non-small
      cell lung cancer cell lines].
AB  - BACKGROUND AND OBJECTIVE: It has been reported that defective expression of
      TGFBR3 was found in non-small cell lung cancer (NSCLC). However, its molecular
      mechanisms remain unclear. The aim of this study is to investigate expression of
      TGFBR3 in NSCLC cell lines and normal human bronchial epithelial cell (HBEpiC),
      and to explore potential molecular mechanisms underlying inactivation of TGFBR3
      gene. METHODS: Western blot was performed to determine the expression of TGFBR3
      in HBEpiC and NSCLC cell lines. Automatic image analysis was carried out to
      estimate relative expression of TGFBR3 protein. We screened for mutation of the
      promoter region of TGFBR3 gene using DNA direct sequencing. Bisulfite-sodium
      modification sequencing was used to detect the methylation status of TGFBR3
      promoter. RESULTS: TGFBR3 protein level was abnormally reduced in NSCLC cell
      lines as compared with HBEpiC. There was significant difference in TGFBR3
      expression between the highly metastatic cell line 95D and non-metastatic cell
      lines, including LTEP-alpha-2, A549 and NCI-H460. No mutation and methylation was
      found in upstream sites -165 to -75 of the proximal promoter of TGFBR3 in HBEpiC
      and NSCLC cell lines. Hypermethylation was shown in upstream sites -314 to -199
      of the distal promoter of TGFBR3 in HBEpiC and NSCLC cell lines. CONCLUSION:
      Reduced expression of TGFBR3 was observed in NSCLC cell lines, especially in 95D,
      suggesting that TGFBR3 might play an important role in development and
      progression of NSCLC and correlate with NSCLC invasion and migration. The
      methylation event occurring at TGFBR3 promoter is not a major cause for reduction
      of TGFBR3 expression.

PMID- 20677642
TI  - [Relationship between single nucleotide polymorphism of the equilibrative
      nucleoside transporter ENT3 and susceptibility to lung cancer].
AB  - BACKGROUND AND OBJECTIVE: The transport of nucleoside transmembrane mediated by
      equilibrative nucleoside transporter (ENT) plays an important role in regulating
      various cellular functions, and the ENT gene may be candidate gene of tumors. The
      aim of this study is to investigate the association between the single
      nudcleotide polymorphism (SNP) of ENT3 and the hereditary susceptibility of lung
      cancer. METHODS: A case-control study was performed involved in 351 lung cancer
      patients and 207 cancer-free controls from Chinese population in Shanghai
      pulmonary hospital. The rs10999776 (C>T) polymorphism was determined by using
      Real-time PCR with AllGlo probes. The frequency distribution of genotypes and
      allele between lung cancer and controls groups was analyzed by chi-square test.
      The association between polymorphism in the ENT3 gene with the risk of lung
      cancer was estimated by computing odds ration (OR) and 95%CI. RESULTS: The
      genotype (CC, TC, IT) and allele distribution of the ENT3 SNP in the patients
      with lung cancer was not significantly different compared with that in controls
      (P > 0.05). Compared with never-smokers with wild homozygous genotype, smokers
      with T allele (TC+TT) had increased risk of lung cancer (OR = 2.848, 95% CI:
      1.536-4.879, P = 0.005), and those with pack-years of smoking more than 30 had
      higher risk (OR = 3.076, 95% CI: 2.308-6.741, P = 0.001). And the risk of
      squamous cell carcinoma significantly increased in smokers, especially those with
      T allele (TC+TI) genotype (OR = 6.066, 95% CI: 2.884-12.758, P < 0.001). The
      genotype with smoking conditions had no significant effect on adenocarcinoma (all
      P > 0.05). CONCLUSION: The results suggested rs10999776 polymorphism may
      implicate in the risk of squamous cell carcinoma in Chinese population which may
      interact with smoking-exposure.

PMID- 20677643
TI  - [The relationship between the TSLC1 silencing and DNA methylation in human lung
      cancer cells].
AB  - BACKGROUND AND OBJECTIVE: The expression of TSLC1 is downregulated or abrogated
      in many kinds of tumors, and its downregulation is highly associated with DNA
      hypermethlyation. The aim of this study is to explore the relationship between
      TSLC1 silencing and DNA methylation of its promoter region in lung cancer cells.
      METHODS: We detected the expression pattern of TSLC1 in human normal lung tissue
      and three lung cancer cell lines (A549, NCI-H446 and Calu-3) by semi-quantitative
      RT-PCR and Real-time PCR. Then we detected the status of DNA methylation in TSLC1
      promoter region with bisulfite sequencing in above normal lung tissue and lung
      cancer cell lines. After treatment of above cell lines with the inhibitor of DNA
      methyltransferase 5-Aza-2-deoxycytidine (5-Aza-dC), we detected the expression
      change of TSLC1 by Real-time PCR before and after the treatment of 5-Aza-dC.
      RESULTS: There was no methylation in TSLC1 promoter region in normal lung tissue
      and A549 cell line in which TSLC1 expressed; while there was DNA hypermethylation
      in TSLC1 promoter region in NCI-H446 and Calu-3 cell lines in which TSLC1 was
      abrogated, also the expression of TSLC1 in NCI-H446 and Calu-3 cell lines could
      be restored after treatment of 5-Aza-dC. CONCLUSION: The silencing of TSLC1 in
      lung cancer cells is due to the hypermethylation of its promoter region.

PMID- 20677645
TI  - [Mechanisms of proliferative inhibition by maimendong & qianjinweijing decoction
      in A549 cells].
AB  - BACKGROUND AND OBJECTIVE: Traditional Chinese medicine is an approach for
      malignant tumor treatment with Chinese characteristics. The aim of this study is
      to investigate the inhibitory effects of Maimendong & qianjinweijing decoction
      extract on A549 human lung cancer cell line proliferation and explored its
      probable molecular mechanisms. METHODS: A549 cells were treated with drugs in
      different does and time. The effects on the proliferation of A549 cells were
      detected by MTT assay and clonogenic assay in vitro. Cell cycle was analyzed by
      flow cytometry. Morphological changes of the apoptosis of cancer cells were
      observed by Hochest 33258 staining. Western blot was performed to detect
      apoptosis-related gene expression. RESULTS: Ethyl acetate extract inhibited the
      growth of A549 cells but not in HFL-1 cells. Compared with controls,
      administration of 10 microg/mLethyl acetate extract resulted in 73.86% decrease
      in colony formation (P < 0.01), apoptotic rates of 33.86% (P < 0.01), and
      morphological changes of apoptosis in A549 cells. The expression of anti
      apoptotic protein EGFR and ERK were significantly down-regulated (P < 0.01).
      CONCLUSION: Ethyl acetate extract might inhibit proliferation and induce
      apoptosis in A549 cells via downregulation of EGFR/ERK signal transduction
      pathway. Therefore, ethyl acetate extract should be further separated in order to
      identify the material fundamentals on anti-cancer effect.

PMID- 20677644
TI  - [Preparation of two types p53 recombinant adenovirus and quantitative exogenous
      expression of green fluorescence protein by flow cytometry].
AB  - BACKGROUND AND OBJECTIVE: The p53 as a transcription factor in cell stress was
      activated to regulate cell cycle and programmed cell death to inhibit tumor
      growth. Usually, p53 is kept in non-activated state through various mechanisms,
      including the action of p53 C-terminal negative regulatory sequences. The purpose
      of the study is to prepare the two types p53 recombinant adenoviruses that carry
      full-length p53 as well as deletion of negative regulatory sequences at p53 C
      terminus and to detect exogenous GFP expression in human lung cancer cell
      infected-virus by FCM scatter plot. METHODS: Using pAdEasy-Track vector system
      the p53 recombinant plasmids was constructed and the homologous recombinants in
      E. coli was produced. The three kinds of recombinant adenovirus in L293 cells was
      generated, sequencing proved. Exogenous GFP expression in human lung cancer 801D
      cells infected-virus was detected by FCM scatter plot. RESULTS: p53 recombinant
      adenoviruses named Ad-p53(wtp), Ad-p53(del) and Ad-(empty carrier) were produced.
      Results of sequences indicate that the Ad-p53(del) was deletion of 111 bases
      before stop codon TGA and of 3 untranslated region at p53, the Ad-p53(wtp) no
      loss of any p53 base, the Ad-(empty carrier) no p53 sequence. FCM scatter plot
      indicate the percentage of 801D cells expressed GFP with three kinds of viral
      infection was almost same and was increased with the virus density. 801D contains
      ratio of cells with different fluorescence intensity. CONCLUSION: The preparation
      of recombinant adenovirus, Ad-p53(del), pA-p53(wtp) and Ad-(empty carrier). The
      cells expressed-GFP can be quantitatively detected by FCM scatter plot. It was
      provide that the reliability of the virus system and accurate method for
      selecting viruses density to infecting cells.

PMID- 20677646
TI  - [Culture of dendritic cells in vitro and its anti-tumor immunotherapy].
AB  - BACKGROUND AND OBJECTIVE: Immunocompromised patients with malignant tumor always
      lack of strong anti-tumor immune response, because the antigenicity of tumor
      cells is weak, and antigen-presenting cell function is low, so that can not be
      effectively presenting tumor antigens to the lymphocytes. Therefore, how to
      effectively induce anti-tumor immune response is the key issue. Through the study
      on establishing a method to culture dendritic cells (DC) in vitro and to observe
      the anti-lung cancer immunological effect induced by DC, we provided definite
      experiment basis for the clinic application of vaccine based on DC. METHODS:
      Through the experiment we get the soluble antigen polypeptide from lung cancer
      cells GLC-82 by 3 mol/L potassium chloride. DCs are cultured and obtained from
      peripheral blood mononuclear cell by GM-CSF, IL-4 and TNF-a. DCs are identified
      by flow cytometer (FCM) and immunostaining. DCs modified by lung cancer tumor
      soluble antigen (TSA) and staphylococcal enterotox in A (SEA), DCs modified by
      TSA or DCs modified by SEA or DCs modified by nothing were cultivated together
      with T lymphocyte, and the obtained cells are named TSA-SEA-DCL or TSA-DCL or SEA
      DCL or DCL as effector cells. The anti-tumor activity of every effector cells
      against target cells was assayed with MT method. Shape of DCs and effector cells,
      and the process of killing target cells were observed in microscope. RESULTS:
      Induced DCs expressed more CD1a, CD80 and HLA-DR, which had typical cell traits
      such as tree branch. The killing ratio of the TSA-SEA-DCL in vitro to GLC-82 is
      larger than TSA-DCL, SEA-DCL and DCL, also larger than to K562. When the effector
      cells cultivate with target cells, we can observe the CTL approach and gather to
      the cancer cell, induce it necrosis and apoptosis. CONCLUSION: Ripe DCs that have
      typical characteristic and phenotype could be induced successfully. High potency
      and relatively specific antilung caner effect can be prepared in virtue ofDC
      Bacterin Induced by lung caner TSA and SEA.

PMID- 20677647
TI  - [Estimation and projection of lung cancer incidence and mortality in China].
AB  - BACKGROUND AND OBJECTIVE: The aim of this study is to analyze lung cancer
      epidemiological trend and estimate lung cancer burden in China. METHODS: Lung
      cancer age specific mortality and incidence rate ratios in different areas and
      sexes were obtained from national cancer registration database in 2004 and 2005.
      Cancer crude mortalities were retrieved from the database of the third national
      death survey, 2004-2005. Age specific incidence rates of lung cancer were
      calculated using mortality and M/I ratios. Annual percent change (APC) was
      estimated by log regression model using Joint Point software by analyzing pooled
      lung cancer incidence data from 10 cancer registries from 1988 to 2005. RESULTS:
      The total estimated new cases and deaths of lung cancer in 2005 were 536 407 and
      475 768 which were higher in male than in female. There was 1.63% increase of
      lung cancer incidence per year from 1988 to 2005, however, the trend showed a
      slowdown by 0.55% annually after adjusted by age. CONCLUSION: Lung cancer is one
      of major health issues in China and the burden is getting serious. Ageing
      population is main cause for increasing incidence and mortality of lung cancer.
      Effective cancer prevention and control is imperative. Especially, tobacco
      control should be carried out in statewide.

PMID- 20677648
TI  - [Advanced NSCLC first pass perfusion at 64-slice CT: reproducibility of volume
      based quantitative measurement].
AB  - BACKGROUND AND OBJECTIVE: The aim of this study is to explore the reproducibility
      of volume-based quantitative measurement of non-small cell lung cancer (NSCLC)
      perfusion at 64-slice CT. METHODS: Fourteen patients with proved advanced NSCLC
      were enrolled in this dynamic first pass volume-based CT perfusion (CTP) study
      (8x5 mm collimation), and they underwent the second scan within 24 h. According
      to the longest diameters, those patients were classified to <3 cm and >3 cm
      groups, and each group had 7 patients. Intradclass correlation coefficient (ICC)
      and Bland-Altman statistics were used to evaluate the reproducibility of CTP
      imaging. RESULTS: In both groups of advanced NSCLC, the reproducibility with BF,
      BV, and PS values were good (ICC > 0.75 for all), but mean transit time (MTT)
      values. For advanced NSCLC (<3 cm), repeatability coefficient (RC) values with
      blood flow (BF), blood volume (BV), MT and permeability surface area product (PS)
      values were 56%, 45%, 114%, and 78%, respectively, and the 95% change intervals
      of RC were -39%-53%, -29%-62%, -83%-145%, and -57%-98%, respectively. For
      advanced NSCLC (>3 cm), those values were 46%, 30%, 59%, and 33%, respectively,
      and the 95% change intervals of RC were -48%-45%, -33%-26%, -54%-64%, and -18%
      48%. CONCLUSION: There is greater reproducibility of tumor size >3 cm than that
      of < or =3 cm. BF and BV could be addressed for reliable clinical application in
      antiangiogenesis therapeutic monitoring with advanced NSCLC patients.

PMID- 20677649
TI  - [Clinical value of serum TPS, CEA, Pro-GRP and CYFRA21-1 in patients with lung
      cancer].
AB  - BACKGROUND AND OBJECTIVE: Serum tumor markers play important roles in diagnosis,
      response and prognosis monitoring for lung cancer. The clinical significance of
      serum level of tissue polypeptide specific antigen (TPS) was investigated in
      diagnosis, response monitoring and prognosis in patients with lung cancer,
      compared with carcinoembryonic antigen (CEA), precursor of gastrin-releasing
      peptide (Pro-GRP) and cytokeratin-19-fragments (CYFRA21-1). METHODS: Blood
      samples of eighty-two patients with lung cancer before treatment and some after
      chemotherapy were measured by ELISA for four tumor markers. RESULTS: Compared
      with lung benign diseases group and health control group, the positive rates and
      levels of TPS, CEA and Pro-GRP in patients with lung cancer were higher, with
      statistically significant difference. TPS in extensive-small cell lung cancer was
      significant higher than that in limited-small cell lung cancer. The positive
      rates and levels of TPS, CEA and Pro-GRP in patients after treatment had
      significant decreases compared with before treatment. TPS was an independent
      prognostic factor of non-small cell lung cancer. CONCLUSION: TPS is valuable to
      diagnosis, response monitoring for patients with lung cancer, moreover, it maybe
      a useful factor of prognosis of non-small cell lung cancer.

PMID- 20677650
TI  - [Association between GSTM1 genetic polymorphism and lung cancer risk by SYBR
      green I real-time PCR assay].
AB  - BACKGROUND AND OBJECTIVE: Glutathione S-transferase M1 (GSTM1) is an important
      phase II metabolic enzyme gene which involves metabolism of various carcinogens
      in human body. Many studies showed that GSTM1 genetic polymorphism was associated
      with lung cancer risk. The aim of this study is to investigate the relationship
      between GSTM1 genetic polymorphism and lung cancer risk among Han nationality
      population in Tianjin district. METHODS: GSTM1 genetic polymorphism was detected
      by melting curve analysis of SYBR green I real-time PCR assay. Two hundred and
      sixty-five histological confirmed lung cancer patients and 307 health controls
      were recruited in this case-control study and the relationship between GSTM1
      genetic polymorphism and lung cancer riskwas investigated. RESULTS: (1) The
      frequency of the GSTMI(-) in lung cancer and control groups was 56.6% and 57.0%
      respectively, and no significant difference was found between the distribution of
      the GSTM1 (-) genotype in the two groups (chi2 = 0.831, P = 0.362). (2) When
      considered the GSTM1(+) genotype as reference, there was no overall statistically
      increased lung cancer risk for carriers with the GSTM1(-) genotype adjusted by
      age, gender and smoking status (OR = 0.840, 95% CI: 0.578-1.221, P = 0.362). (3)
      The frequency of the GSTM1(-) genotype for squamous cell carcinoma,
      adenocarcinoma, SCLC and other histological types was 65.8%, 48.5%, 47.8% and
      52.2% respectively, compared with the control group, no statistically increased
      lung cancer risk was observed (P > 0.05). CONCLUSION: No evidence is found
      between GSTMI genetic polymorphism and lung cancer risk among Han nationality
      population in Tianjin district.

PMID- 20677651
TI  - [A case-control study on non-smoking primary lung cancers in Sichuan, China].
AB  - BACKGROUND AND OBJECTIVE: The incidence of lung cancer in non-smokers is
      increasing in recent years. The aim of this investigation is to explore main risk
      factors of non-smoking primary lung cancers in Sichuan province in order to
      provide more accurate data for clinical. METHODS: One hundred and fourty-five non
      smoking pairs of cases and 145 of controls were matched by age and sex. The
      patients were newly-diagnosed definitely as primary lung cancer at West China
      Hospital of Sichuan University from March to December 2009. RESULTS: Seventeen
      exposure factors were explored as epidemic agents for non-smoking lung cancer in
      Sichuan by using univariate analysis; mutivariate conditional Logistic regression
      analysis showed that passive smoking, moved into newly renovated homes over the
      past 10 years, family cancer history from second/ third-degree relatives, lack of
      emotion regulation, heavy work pressure and poor quality of sleep were main risk
      agents for the non-smoking lung cancer incidence with OR 2.267 (95% CI: 1.231
      4.177), 5.080 (95% CI: 1.632-15.817), 7.937 (95% CI: 1.815-34.705), 2.491 (95%
      CI: 1.230-4.738), 5.769 (95% CI: 2.030-16.396), 2.538 (95% CI: 1.277-4.861),
      respectively. While higher body mass index, eating fruit and vegetable and
      regular participating in physical exercise might be protective factors with OR
      0.419 (95% CI: 0.226-0.779), 0.344 (95% CI: 0.155-0.762), 0.507 (95% CI: 0.274
      0.937), respectively. CONCLUSION: The occurrence of non-smoking primary lung
      cancer associated with a variety of exposure factors including passive smoking,
      history of exposure to harmful environmental, family cancer history, mental and
      psychological factors in Sichuan Province.

PMID- 20677652
TI  - [Expression of PAH-DNA adducts in lung tissues of Xuanwei female lung cancer
      patients].
AB  - BACKGROUND AND OBJECTIVE: The coal-fired pollution in Xuanwei area has been
      considered to be local main reason for high incidence of female lung cancer. The
      aim of this study is to explore the expression of PAH-DNA adducts in lung tissues
      of Xuanwei female lung cancer patients and to explore the relationship between
      the large number of coal-fired pollution PAHs materials and the high incidence of
      Xuanwei female lung cancer. METHODS: We totally collected each 20 cases of
      Xuanwei female lung cancer patients, Xuanwei male lung cancer patients, Non
      Xuanwei female lung cancer patients and collect each 10 cases of Xuanwei, Non
      Xuanwei female patients with benign lung lesions. The cancer tissues, adjacent
      cancer tissues and normal lung tissues were collected in lung cancer patients and
      only the normal tissues were collected in benign lung lesion patients. There were
      total 80 cases and 200 tissues. Immunofluorescence was used to detect the
      expression of PAH-DNA adducts in each group. Image pro-plus 6.0 software was used
      to analyze the images and part quantified analysis. SPSS 13.0 statistical
      software was used to analyze the data. RESULTS: The positive expression of PAH
      DNA adducts in lung cancer tissues, adjacent cancer tissues and normal lung
      tissues of Xuanwei female lung cancer patients were 90%, 80% and 65%. They were
      higher than the positive expression of PAH-DNA adducts in Xuanwei male lung
      cancer patients (35%, 30%, 30%) and Non-Xuanwei female lung cancer patients (20%,
      15%, 10%) (P < 0.01). The expressions in lung tissues ofXuanwei female benign
      lung lesion patients (positive expression is 70%) were higher than it in Non
      Xuanwei female benign lung lesion patients (positive expression is 10%). With the
      direction changing from cancer tissues, adjacent cancer tissues to normal lung
      tissues, the expressions of PAH-DNA adducts were decreased but had no statistical
      difference (P > 0.05S). CONCLUSION: The expressions of PAH-DNA adducts in lung
      tissues of Xuanwei female were higher than which in Xuanwei male and Non-Xuanwei
      female.

PMID- 20677653
TI  - [ERCC1 expression as a predictor of survival after operation in stage I non-small
      cell lung cancer patients].
AB  - BACKGROUND AND OBJECTIVE: Proteins of the nucleotide excision repair pathway can
      repair DNA damage. The excision repair cross-complementing (ERCC) gene family
      reduce damagement of DNA by nucleotide excision and repair. The aim of this study
      is to investigate the expressions of ERCC1 (members of DNA repair gene family) in
      patients with non-small cell lung cancer (NSCLC) as well as their clinical
      prognostic significance. METHODS: Expression levels ofERCC1 were detected by IHC
      in 118 stage I NSCLC patients. Kaplan-Meier survival curve, and Cox multivariate
      regression analysis were used for statistical analysis. RESULTS: The patients
      with high expression of ERCC1 had significantly longer survival time than those
      with low expression of ERCC1, and Cox multivariate regression analysis showed
      that expression of RRM1 was an independent prognostic factor for NSCLC patients.
      CONCLUSION: NSCLC patients with high ERCC1 expression have a better survival when
      compared to patients with low ERCC1 expression. Therefore, an intact DNA repair
      mechanism may reduce the accumulation of genetic aberrations that are thought to
      contribute to a tumor malignant potential and therefore the risk of relapse after
      definitive treatment.

PMID- 20677654
TI  - [The association of XPD G312A polymorphism with lung cancer risk: a meta
      analysis].
AB  - BACKGROUND AND OBJECTIVE: It has been proven that close relation was existed
      between XPD polymorphism G312A and lung cancer risk. However, some of the results
      are not consistent. The aim of this study is to explore the impact of DNA repair
      gene XPD polymorphism G312A on lung cancer risk. METHODS: The literatures
      eligible from PUBMED, EMBASE, CNKI and WANGFANG database were enrolled in the
      meta-analysis. Heterogeneity among combined studies was assessed. The pooled OR
      and 95%CI were calculated. The sensitivity analysis and the publication bias were
      evaluated by RevMan 5.0 and STATA 11.0. RESULTS: There were 6554 cases and 8322
      controls from 18 studies included in the meta-analysis. In total, individuals
      with 312A allele and 312AA genotype showed increased lung cancer risk (A vs. G:
      OR = 1.06, 95% CI: 1.00-1.12; AA vs. AG+GG: OR = 1.20, 95% CI: 1.06-1.36; AA vs.
      GG: OR = 1.19, 95% CI: 1.04-1.36). In Asians, individuals with 312AA genotype
      showed 6.15 fold and 6.20 fold increased lung cancer risk in recessive genetic
      model and homogenous contrast respectively (AA vs. AG+GG: OR = 7.15, 95% CI: 1.90
      26.94; AA vs. GG: OR = 7.20, 95% CI: 1.91-27.15). In Caucasians, individuals with
      312AA genotype showed a 15% increased lung cancer risk (OR = 1.15, 95% CI: 1.01
      1.31). CONCLUSION: XPD 312A allele is risk allele for lung cancer. Individuals
      with AA genotype have higher risk of lung cancer, especially in Asians.

PMID- 20677655
TI  - [A systematic review on different treatment methods of bone metastasis from
      cancers].
AB  - BACKGROUND AND OBJECTIVE: Skeletal metastase is one of the most common
      complications related to advanced cancer. The aim of this study is to analyze the
      effectiveness and safety of radiotherapy plus intravenous bisphosphonates versus
      radiotherapy alone for treating bone metastasis. METHODS: We searched the
      Cochrane Library, PubMed, EMBASE, CBM, CNKI and VIP, as well as the reference
      lists of reports and reviews. The quality of included trials was evaluated by the
      Cochrane Handbook. Data were extracted and evaluated by two reviewers
      independently. The Cochrane Collaboration's Rev-Man 5.0 was used for data
      analysis. RESULTS: Twenty-two trials involving 1 585 patients were included.
      Compared with radiotherapy alone, radiotherapy plus intravenous bisphosphonates
      was more effective in total effective rate of pain relive (RR = 1.21, 95% CI:
      1.13-1.30, P < 0.001), average abated time (WMD = 16.00, 95% CI: 10.12-21.88, P <
      0.001), and quality of life (RR = 1.25, 95% CI: 1.08-1.45, P = 0.003, with
      significant differences. Side effects have no significant differences between the
      two groups except fever (RR = 5.61, 95% CI: 3.11-10.13, P < 0.001). CONCLUSION:
      Current evidence supports more effective of radiotherapy plus intravenous
      bisphosphonates for bone metastases. The combine treatment is safe and effective.

PMID- 20677656
TI  - [Analysis of 41 cases of primary hypervascular non-small cell lung cancer treated
      with embolization of emulsion of chemotherapeutics and iodized oil].
AB  - BACKGROUND AND OBJECTIVE: Transcatheter arterial chemotherapy and embolization is
      the main method in the treatment of lung cancer, but most of the reports do not
      study individually to small cell lung cancer (SCLC), non-small cell lung cancer
      (NSCLC), hypovascular and hypervascular lung cancer. The pre-embolization
      perfusion of hemotherapeutics is still being used routinely and seldom report to
      iodized oil embolization. The article summarized the quality of life after the
      treatment, clinical efficiency, survival time and complications to evaluate the
      clinical effect of primary hypervascular NSCLC treated with embolization of
      emulsion of chemotherapeutics and iodized oil. METHODS: The study totally
      analyzed 41 cases which confirmed by pathology and follow up study from January,
      2008 to January 2009. The CT scan with IV contrast demonstrates over moderate
      enhanced lesion which indicate hypervascular. Within the 41 cases, 23 cases of
      central, 18 cases of peripheral. Suqamous carcinoma 21 cases, adenocarcinoma 15
      cases and squamoadenocarcinoma 5 cases. Stage IIIb 34 cases, stage IV 7 cases.
      Superselective incubation with microcatheter under DSA, to embolize the capillary
      bed with liquefied iodized oil and the emulsion of pharmorubicin, to embolize the
      supply artery of the tumor with gelatin foam microparticle. The liquefied iodized
      oil 5 mL-10 mL, pharmorubicin 10 mg-30 mg. The longest follow up is 12 months and
      to compare with the references of 2007-2009. RESULTS: The KPS is widely acclaimed
      after the treatment (P < 0.05), no complete response (CR), 31 cases of partial
      response (PR), 7 cases of no change (NC) and 3 cases of progressive disease (PD),
      the total efficiency (CR+PR) is 75.6%. The clinical efficiency (CR+PR+NC) is
      92.68%. 33 cases of total survival tome over 12 months (80.48%), IIIb stage 29/34
      (85.29%), IV stage 4/7 (57.14%). 1 case with severe complication-spinal injury.
      CONCLUSION: To treat primary hypervascular NSCLC with simple embolization of
      emulsion of chemotherapeutics and iodized oil is very useful and can avoid the
      side effect of chemotherapeutics. The key point to avoid spinal injury and other
      severe complications is to distinguish the spinal aretery and intratumor AV
      fistula by using superselective incubation with microcatheter under DSA.

PMID- 20677657
TI  - [Advances on treatment of small cell lung cancer with amrubicin].

PMID- 20677658
TI  - [Pleuropulmonary blastoma: a clinicopathological analysis].
AB  - BACKGROUND AND OBJECTIVE: Pleuropulmonary blastoma (PPB) is a rare malignant
      tumor with unique clinicopathological features. The aim of this study is to
      investigate the clinicopathological features, the diagnosis and differential
      diagnosis of pleuropulmonary blastoma. METHODS: Five cases of PPB were analyzed
      by light microscopy, immunohistochemistry and their clinical data, and the
      relative literatures were reviewed. RESULTS: Five cases of patients suffered from
      PPB were aged from 21 to 47 months (mean 32.8 months). Most of the masses were
      located in the thoracic cavities and 4 cases accompanied with pleural effusions.
      Histologically, these tumors included 1 case of type I PPB which showed pure
      cystic architecture; 2 cases were type II PPB which showed cystic and solid
      masses accompanied with rhabdomyoblastic differentiation and nodules of
      cartilage; the other 2 cases were type III PPB and characterized by absolute
      solid masses with anaplastic undifferentiated sarcomatous components.
      Immunohistochemical studies showed that tumor cells were positive for Vimentin
      and some for Desmin and Myogenin, the nodules of cartilage were positive for S
      100. The tumor cells were negative for PCK, EMA and CD99. CONCLUSION:
      Pleuropulmonary blastoma is a rare and highly aggressive malignancy arising in
      the lung and pleural of infancy and early childhood. The type I, II and III PPB
      have unique clinicopathological features respectively. This kind of tumor should
      be distinguished from some benign and malignant diseases such as congenital
      cystic adenomatoid malformation (CCAM) and embryonal rhabdomyosarcoma.

PMID- 20677659
TI  - [Case report: pulmonary typical carcinoid with multi-organ metastasis].

PMID- 20677660
TI  - [Huge primary pulmonary lymphoma: a report of one case and review of the
      literature].

PMID- 20677661
TI  - [Synchronous lung cancer in operation and brain infraction].

PMID- 20677662
TI  - [Epidemiological and economic aspects of chelating therapy in the therapeutic
      center of thalassemia in Morocco].
AB  - The study aims to give a general idea about the new experience of chelating drugs
      among beta-thalassemia patients. It is a declarative survey. It was done in the
      therapy center of Morocco. Statistics were done in the Laboratory of Biological
      Essays in Kenitra. All economic and pharmacological data were given by Novartis.
      Sample size was 89. The only treatment available now in the therapy center is
      deferiprone. 78% of patients attending the service regularly take deferiprone as
      treatment while 13% of them combine deferiprone and deferoxamine. Most of the
      patients take treatments regularly. Chelators have reduced mortality. Patients
      taking deferoxamine experienced injection site reactions. Most of ADR due to
      deferiprone were digestive. In conclusion, the main problem with chelators in
      Morocco is lack of accessibility to drugs (except for some patients insured or
      payant).

PMID- 20677663
TI  - [Risk factors of osteonecrosis of the femoral head following slipped capital
      femoral epiphysis].
AB  - Osteonecrosis is a serious complication of the treatment of slipped capital
      femoral epiphysis. The purpose of this study was to identify factors predisposing
      to the development of this complication. We reviewed retrospectively 127 patients
      (150 hips) treated for slipped capital femoral epiphysis in our institution
      between 1980 and 2004. Clinical and radiological data were analyzed before and
      after treatment, and at consecutive follow-up examination. Osteonecrosis was
      defined in the basis of radiological criteria. The risk of development of
      osteonecrosis was correlated with multiple clinical and radiographic parameters.
      RESULTS: 12 hips in 11 patients (8%) had development of osteonecrosis. Ten of
      them had an unstable slip. From 130 stable hips, regardless of grade, two had
      development of osteonecrosis. In patients who had presented with an unstable hip,
      the risk of osteonecrosis increased with the grade of the slip. Osteonecrosis was
      more likely to develop in hips that had been treated with multiple screws than in
      those who had been treated with a single screw. In conclusion, partial or
      complete reduction of an unstable slipped capital femoral epiphysis increases the
      risk of development of osteonecrosis. Pinning in situ without reduction with a
      single screw is the method of choice of the treatment of a slipped capital
      femoral epiphysis.

PMID- 20677664
TI  - [Twenty-five years of calcineurin inhibitors use in kidney transplantation at
      Erasme Hospital].
AB  - The results and risk factors within a cohort of 1.380 renal allografts treated
      with a calcineurin inhibitor from 1983 to 2008 at Erasme Hospital were analyzed.
      Three groups corresponding to successive periods were compared: A, from 1983 to
      1992 (n = 463); B, from 1993 to 2000 (n = 470); C, from 2001 to 2008 (n = 447).
      Patient's survival was lower during period C than during periods A and B (89 vs
      85% at 8 years, P = 0,044), due to the recipients age. In contrast, graft
      survival raised gradually (64, 76 and 81% at 8 years for periods A, B and C
      respectively, P < 0,001). Several factors significantly influence graft survival:
      in decreasing order, they are the recipient's age (reduced risk of rejection with
      age), immunosuppressive protocol (superiority of mycophenolate mofetyl and
      induction with antibodies directed to the IL2 receptor), HLA sensitization,
      number of HLA-B+Dr mismatches between recipient and donor, and gender (opposite
      effects of recipient's and donor's gender). The permanent evaluation of results
      using multivariate analyses would allow to promptly adapt selection and
      therapeutic strategies within each transplantation center.

PMID- 20677665
TI  - [Are extra costs generated by patients justifiable? Methodology and results from
      a study carried out in a Belgian general hospital].
AB  - Cost outliers account for 6 to 8% of hospital inpatient stays and concentrate 22
      to 30% of inpatient costs. Explanatory factors were highlighted in various
      studies. They are the lenght of stay, an intensive care unit stay, the severity
      of illness index related to DRG and social factors. Patients are not always
      explained by these factors. The objective of this study is to analyse cases not
      explained by those factors, through a detailed analysis of medical files. In the
      studied hospital, there are 6,3% high cost outliers and 1,1% low cost outliers.
      These stays were isolated on the basis of a rule based on percentiles. Extra
      costs generated by high cost outliers are 6.999 euro per stay. The extra lenght
      of stay for these patients is 20,42 days. Among the 454 patients high cost
      outliers, 334 patients are explained by factors extracted from a statistical
      analysis based on a logistic regression (intensive care unit stay, severity of
      illness index, lenght of stay and social factors). The analysis of medical files
      of the 120 not explained inpatient stays highlights new explanatory factors
      (coding errors, heterogeneity of DRGs, etc.). At the end of this study, the
      conclusion is that a statistical analysis combined with a precise analysis of
      medical files allowed to explain the majority of cost outliers. An explanation is
      however not necessarily synonymous with medical justification.

PMID- 20677666
TI  - [The post-traumatic stress disorder--PTSD--in psychiatry by children and
      teenagers: diagnostic and treatments].
AB  - News confronts us daily with various traumatic events, like armed conflict,
      terrorist attacks, natural disasters, not to mention the cases of abuse and
      incest. The impact of these traumas on the psychological development of children
      is often very important and we can observe among them, symptoms of severe mental
      traumatisms immediately and sometimes deferred. The purpose of this paper is to
      highlight the existence of this disorder by children, to develop its symptoms and
      its possible developments, and to address the different therapeutic approaches.

PMID- 20677667
TI  - [Pulmonary nodule: a bayesian approach].
AB  - A solitary pulmonary nodule is a common clinical problem. It is usually detected
      incidentally. The prevalence of solitary pulmonary nodule (SPN) in the lung
      cancer screening study varies from 8 to 50% (with a prevalence of malignant
      nodule from 1 to 13%). The bayesian approach can help us to identify promptly
      malignant nodule in order to treat them surgically and to avoid surgery for
      benign nodules. Therefore, it is needed to estimate the probability of cancer
      (Pca) in the SPN. Likelihood ratio (LR) for overall prevalence of malignancy and
      for different clinical and radiological information (age, smoking exposure,
      symptoms, cancer history, nodule size, spiculation, calcification, location,
      growth...) can be obtained from the literature. The odds of cancer-malignancy
      (odds ca) can be calculated by multiplying all of these LRs together. The Pca =
      odds ca/1+odds ca. Using this bayeasian approach, the probability of cancer based
      on an abnormal or normal fluoro-2-deoxy-D-glucose-positron emission tomography
      (FDG-PET) scan has been estimated. Sensitivity, specificity, positive predictive
      value and negative predictive value of PET scan are respectively about 90%, 83%,
      92% and 90%. Moreover, the LR for malignancy are higher with an abnormal PET scan
      when compared to most clinical and radiological LRs. Today, the Bayesian approach
      of SPN must include PET scan.

PMID- 20677668
TI  - [A case of von Hippel-Lindau disease diagnosed at the autopsy].
AB  - A 46-year-old woman presents with walk instability. A diagnosis of cerebellar
      hemangioblastoma is made on MRI and neurosurgical excision was performed. In the
      postoperative course, the patient died of a bulbar cerebral stroke with
      respiratory distress. At the autopsy, the finding of a bilateral renal clear cell
      carcinoma in addition to the cerebellar hemangioblastoma allows for the diagnosis
      of von Hippel-Lindau disease. It is an inherited, autosomal dominant syndrome
      charaterized by a VHL gene mutation. Affected individuals are at risk of
      developing various benign and malignant tumors of multiple organs, reviewed in
      this article. Despite a decrease of number of necropsy, this case as the review
      of literature demonstrates clinical importance of autopsy.

PMID- 20677670
TI  - [Chronic exposure to organochlorine compounds and health effects in adults:
      diabetes and thyroid diseases].
AB  - Organochlorine compounds are widely distributed in the world and may persist in
      both the environment and living organisms. They are fat-soluble compounds and
      people are usually exposed to them through food, inhalation or dermal contact.
      They are classified as POPs (persistent organic pollutants), as they persist in
      the environment for a long time and move up through the food chain. DTT and other
      synthetic pesticides, polychlorinated dibenzodioxins (PCDD), polychlorinated
      dibenzofurans (PCDF) and polychlorobyfenils (PCB) are among the most diffused
      POPs worldwide. Experimental studies show that some of these chemicals have
      endocrine disruption activity and particularly that they can alter the thyroid
      function. Furthermore, recent studies in humans show that exposure to some
      organochlorine compounds may increase the risk of type II diabetes mellitus. This
      review provides a synthesis of the results of epidemiologic studies regarding the
      association between organochlorines exposure and thyroid diseases and diabetes.
      We included published studies with measures of internal dose of exposure
      (usually, serum concentration) in adults. We retrieved 22 studies for thyroid
      diseases and 22 on diabetes. Overall, we found contrasting results among the
      studies, with about half of them showing a statistically significant association
      between serum concentration of organochlorines and the diseases investigated.

PMID- 20677669
TI  - [Edouard Kufferath (1853-1909), eminent figure of past gynaecology and obstetrics
      at the ULB (Universite libre de Bruxelles)].
AB  - Edouard Kufferath (1853-1909) came from a German family of musicians. He was
      appointed as professor of obstetrics for 20 years and was Rector of the ULB
      (Universite libre de Bruxelles) in 1905-1906. He was the first in Belgium to
      apply strict aseptic rules in obstetrics and to obtain hence a drastic reduction
      of maternal and newborn mortalities consecutive to puerperal fever. He improved
      the technique of symphyseotomy and invented a new method of labour induction. The
      type of obstetrical forceps that he conceived was known by his name and remained
      widely used by obstetricians in Brussels during at least six decades before the
      diffusion of the Swedish vacuum extractor. The exceptional quality of Kufferath's
      teaching was unanimously recognized. He became also active as communal Counsellor
      of the City of Brussels. Unanimously admired and respected, he prematurely passed
      away from a tongue cancer at the age of 55 years, covered with official honours.

PMID- 20677671
TI  - Socio-demographic survey of first degree healthcare students in the 2007-08
      academic year in an Italian university.
AB  - This study examines the socio-demographic characteristics of first-year students
      on first degree healthcare courses at Udine University (Italy). The survey tried
      to elicit useful information in a field where literature is scarce. Every student
      starting healthcare courses in the 2007/08 academic year was contacted and asked
      to fill in a questionnaire. Two hundred and sixty students were identified,
      belonging to six different courses: Nursing Sciences, Obstetric Sciences,
      Physiotherapy, Radiography, Neurophysiopathology Techniques, Biomedical
      Laboratory Techniques. Each questionnaire included 26 items (25 closed and one
      open) and had four sections: personal data, family data, training background,
      criteria affecting the decision to attend a healthcare course. The overall
      response rate was 87% (226 out of 260). Major findings were: women prevail on men
      (77% vs. 23%), many students chose these courses because some family member
      worked in the healthcare field (22.1%), 19.9% of students are older than 26 and
      7.1% of them are postgraduates, 12% come from foreign countries, and job
      opportunities and former work experience influenced the choice of course. This
      database provides an important benchmark for comparing future trends among
      students in the healthcare profession in terms of socio-demographic
      characteristics and personal attitudes.

PMID- 20677672
TI  - [Perceived quality assessment in the University Hospital Authority in Sassary,
      Italy].
AB  - In line with the health legislation that introduced a system to monitor and
      review the quality, the Hospital Authority of University of Sassari has placed
      among its main objectives the satisfaction of patients/clients and has made an
      initial assessment of customer satisfaction for users hospitalized in their
      facilities with the methodology of the questionnaire. It was drawn up a
      questionnaire to closed questions, with default value scales, divided into 4
      areas: 1) Hospitality, 2) Hotel treatment, 3) Professionalism of staff
      information related pathology, informed consent, 4) personal opinion of the
      patient upon discharge. The questionnaire was administered the day of discharge,
      to users hospitalized of six UO of Hospital Authority in the months of September
      and October 2009, and patients discharged within 2 months were given a total of
      514, of them have completed the testing 290 (54% of discharged patients). The
      questionnaires were analyzed in the results of both the individual UO involved in
      both the overall result, persons responsible for each facility was sent a report
      with the results of its own. The survey results are satisfactory with regard to
      both positive aspects, that is the overall grade average of 86.23% which to
      criticism, to which they are planning initiatives for their solution.

PMID- 20677673
TI  - [Implementation of methods for detection of perceived quality: the application of
      the Picker's method in ASL Napoli 1 DS 50].
AB  - The evaluation of the patient satisfaction in primary care is quite difficult to
      evaluate for lack of appropriate indicators. The objectives of this study were
      the validation of the method, using the Picker Institute's Inpatient
      Questionnaire, and the assessment of patient judgment about the quality of
      primary care in the DS 50. The indicators that have been used included 3 areas:
      communication, organization and patient-staff relationship. The results showed
      that the patient-staff relationship area was indicated as the most important for
      the patients and they pointed out several problem either for human (self
      reference of the professional, lack of emotional relationship) and or for
      organizational aspects (waiting time). The study highlight that in order to
      improve the utility of such method, the health organization must be able to
      appropriately evaluate the patients' need, setting them in a specific
      organizational vision.

PMID- 20677674
TI  - [Gray water reuse in domestic environment: implications for public health].
AB  - The Authors describe the main microbiological characteristics of gray and rain
      waters, the evidence of infections related to the reuse of such waters and the
      main Italian and international standards and guidelines in this regard. In light
      of the review, the authors conclude that the limits defined by the Italian
      regulations are very precautionary and should ensure a very low risk of bacterial
      and/or viral infection (< 10.5 and 10.9 cases/year). It remains an open problem
      the risk of parasitic infections, for which the evidences to draw final
      conclusions are not sufficient yet.

PMID- 20677675
TI  - [The treatment of varicose veins of the lower limbs: the organizational
      appropriateness in Italy from 1999 to 2006].
AB  - The treatment of varicose veins is a major topic for National Health Services
      because of high prevalence of this disease. The development of minimally invasive
      varicose veins surgery allowed the treatment as a day case in a hospital setting.
      Our research analysed the differences between day hospital and ordinary
      interventions for varicose veins surgery in Italy; furthermore, our research
      compares the trend of Day Surgery hospitalizations in Italy with the results of
      the English National Health System. The proportion of Day surgery interventions
      on the total of varicose veins interventions has considerably increased in Italy
      from 1999 to 2006, although the development of minimally invasive varicose veins
      surgery in Italy is slower compared to England. Starting from 2003 the Day
      Surgery treatment for ligature and stripping of varicose veins has gradually
      increased in Italy. This result is due to the impact of different regulatory
      level planning, managerial and clinical skills in hospital setting favouring the
      development of alternative treatments to the ordinary hospitalization.

PMID- 20677676
TI  - [In the heart of the district. 50 interviews with the health professionals of the
      Lazio Region districts, Italy].
AB  - This article aims to explore some key issues relating to the health districts of
      the Lazio Region, in particular the major critical aspects as well as some
      strengths highlighted by the operators. In the Lazio Region there are 12 Local
      Health Units, divided into 55 health districts. In recent years, the majority of
      the authors analized theoretical models proposed by regional standards, while the
      strengths and weaknesses of the district, as well as the organizational
      difficulties and problems experienced daily by the operators have not been
      investigated. It was decided to use qualitative methods of research, through open
      interviews with 50 operators in 15 health districts of the Region. Interviews
      were analysed utilizing software Nvivo. Some codes were identified to guide
      interviews. We can summarize the emergency issues at least in three major areas:
      1) the organization of the district, 2) the management of personnel and
      resources, 3) the care pathways. It is hoped that, during next years, the
      research directed at health district analysis will grow, with particular
      reference to quantitative and qualitative investigations, in order to build a
      body of knowledge from practical experience of health professionals.

PMID- 20677677
TI  - [Organ allocation. Ethical issues].
AB  - The criteria for allocating organs are one of the most debated ethical issue in
      the transplantation programs. The article examines some rules and principles
      followed by "Nord Italia Transplant program", summarized in its Principles'
      Charter and explained in a recent interdisciplinary book. General theories of
      justice and their application to individual clinical cases are commented and
      evaluated, in order to foster a public, democratic, transparent debate among
      professionals and citizens, scientific associations and customers' organizations.
      Some specific moral dilemmas are focused regarding the concepts of proportionate
      treatment, unselfish donation by living persons, promotion of local institutions
      efficiency.

PMID- 20677678
TI  - [Research Ethics Committees in Abruzzo: criticisms and prospects for
      developments].
AB  - The first legislative bills on Ethics Committee (EC) activity were adopted across
      the Italian Regions simultaneously (1998). This widespread implementation meant
      it was necessary to define new qualitative and quantitative standards (Decree
      Law, 12th May 2009), creating expectations about the EC's role in research and
      clinical practice and its potential to improve the quality of medical assistance.
      The present paper presents the results of a descriptive survey that maps out the
      framework, organization and operating methods of ECs in the Abruzzo Region in
      Italy. Differences between ECs have been outlined, with special concern for
      differences in organization and way of operating. It was found that interaction
      between the EC and the experimenter is limited to the authorization phase of the
      research protocol, with low level involvement in the planning and execution
      phases. Additionally, the exchange of information between the co-ordinating EC
      and EC practitioners is not well organized in multicentre experimentation. A
      certain amount of criticism emerged regarding those areas of activity that would
      help to place the EC at the centre of the cultural growth process with regards to
      Bioethics and Clinical Research (e.g. education, on-line news on Bioethics
      topics).These criticisms are part of the reality of the Abruzzo Region that lacks
      economic and structural resources which penalizes EC activity.

PMID- 20677679
TI  - A/H1N1: effectiveness of prevention in childhood.
AB  - The question on how to manage the presence of the pandemic virus A/H1N1 in
      schools when the specific vaccine was not yet available was based on
      environmental and behavioural interventions. Some countries have decided to
      postpone the opening of schools to avoid the epidemic peak, others have preferred
      to wait for the mass vaccination to contain the epidemic. WHO has issued a
      briefing note in which measures to be taken in school activities to limit the
      spread of virus A/H1N1 were detailed. In our experience, the education of
      students towards good hygiene practices has given interesting results.

PMID- 20677680
TI  - [Must, can, want to].

PMID- 20677681
TI  - [Nursing risk diagnoses are not a weather forecast].

PMID- 20677682
TI  - [A nationwide network for nursing consultation is established: supporting advice
      seekers].

PMID- 20677683
TI  - [Still too many disabled patients and family caregivers misjudge new support
      chances: legal right to nursing consultation].

PMID- 20677684
TI  - [Reflections on language in health care--1: Promoting health with language].

PMID- 20677685
TI  - [Engagement of voluntary helpers in the hospital: volunteering feels good].

PMID- 20677686
TI  - [Electronic data processing of nursing documentation--implementation in nursing
      practice: are the effort and costs worthwhile?].

PMID- 20677687
TI  - [Current and systematic pain assessment: the pain diary].

PMID- 20677688
TI  - [Implementation of the nursing process in the hospital: practical, experienced
      nursing process--utopia or reality? ].

PMID- 20677689
TI  - [Implementing new information technologies in nursing: legal aspects].

PMID- 20677690
TI  - [Expression of the self determination right of the patient: the right to access
      of hospital records].

PMID- 20677691
TI  - [The significance of documentation in clinical routine: we are all in one boat].

PMID- 20677692
TI  - [Self-images and perceptions of other professions among students of nursing,
      physiotherapy, and occupational therapy and their importance for
      interprofessional cooperation].
AB  - INTRODUCTION: Interdisciplinary cooperation is necessary to provide effective and
      high quality treatment for clients of the health care system. Interaction between
      professional groups depends on how their members perceive their self-image and
      the image of other professions. METHOD: Within the framework of the project
      "Quality in the education of health-professionals" a qualitative study with 23
      nurses, 24 physiotherapists and 15 occupational therapists in the second or third
      year of training was conducted. Participants were asked to report their self
      image and the image of the other two professions. A qualitative content analysis
      according to Mayring was used for data analysis. RESULTS: Four categories emerged
      that allowed describing the self image and the image of the other professions:
      roles of the respective health professions, relation of the health professionals
      to their clients, attributes that typically characterized members of a particular
      profession, and relationship between the health professions. DISCUSSION: Latent
      conflicts between professional groups became apparent. Contradicting perceptions
      are due to subjective bias in favour of the own professional group.
      Interdisciplinary collaboration requires a new culture of co-operation.

PMID- 20677693
TI  - [Planning a practical instructional situation--9: Measuring blood glucose].

PMID- 20677694
TI  - [From case to case: information technology in nursing].

PMID- 20677696
TI  - Quantum questions.

PMID- 20677695
TI  - [Recognizing and understanding disorders: hypertension as the leading symptom].

PMID- 20677697
TI  - Von Bezold assimilation effect reverses in stereoscopic conditions.
AB  - Lightness contrast and lightness assimilation are opposite phenomena: in
      contrast, grey targets appear darker when bordering bright surfaces (inducers)
      rather than dark ones; in assimilation, the opposite occurs. The question is:
      which visual process favours the occurrence of one phenomenon over the other?
      Researchers provided three answers to this question. The first asserts that both
      phenomena are caused by peripheral processes; the second attributes their
      occurrence to central processes; and the third claims that contrast involves
      central processes, whilst assimilation involves peripheral ones. To test these
      hypotheses, an experiment on an IT system equipped with goggles for stereo vision
      was run. Observers were asked to evaluate the lightness of a grey target, and two
      variables were systematically manipulated: (i) the apparent distance of the
      inducers; and (ii) brightness of the inducers. The retinal stimulation was kept
      constant throughout, so that the peripheral processes remained the same. The
      results show that the lightness of the target depends on both variables. As the
      retinal stimulation was kept constant, we conclude that central mechanisms are
      involved in both lightness contrast and lightness assimilation.

PMID- 20677698
TI  - Colour constancy: influence of viewing behaviour on grey settings.
AB  - In numerous studies on colour constancy or colour induction subjects have to
      adjust a test field so that it looks achromatic. Their viewing behaviour during
      these settings is often not controlled or reported. Here I show that the results
      of grey settings depend on whether subjects visually explore the stimulus by
      looking around or fixate their gaze exclusively on the test field. Two different
      viewing instructions are compared with regard to the degree of constancy as
      measured by the shift of grey settings in coloured surrounds. In variegated
      surrounds (but not in uniform surrounds) there is a robust effect of viewing
      condition for all subjects and all surround chromaticities tested, in that
      exploration increases colour constancy compared to fixating the test field.
      Values of a colour constancy index are increased by as much as 20% (where 100%
      colour constancy means that the subject chooses as grey the mean chromaticity of
      the surround) with an average across all subjects and surrounds of 12.6%. Thus,
      if this factor is not experimentally controlled, it could inflate variance,
      reduce comparability between different studies, and even lead to unwarranted
      conclusions if viewing behaviour unpredictably differs between experimental
      conditions.

PMID- 20677699
TI  - Adaptation to combinations of form, colour, and movement.
AB  - Observers typically report illusory colour on achromatic gratings after being
      adapted to orthogonally oriented gratings presented in complementary colours,
      where the colour apparent on each grating is complementary to the one that had
      been presented with that grating during adaptation (McCollough, 1965 Science 149
      1115-1116). We used this procedure, but presented homogenous fields at test
      instead of achromatic gratings. When adaptation stimuli moved in directions
      locally orthogonal to their orientation, we found that, for up to 7-8 min after
      adaptation, a flower-like illusory pattern was evident on both homogenous fields;
      after this time illusory radial lines and concentric circles were evident and
      were colour-contingent (eg for adaptation with green concentric circles and
      magenta radial lines, concentric circles were apparent on a magenta test field
      and radial lines were apparent on a green test field). When stimuli were
      stationary during induction, colour-contingent illusory forms were also apparent
      at test. The results demonstrate that an aftereffect, reciprocal to the
      McCollough effect, can be produced under appropriate induction conditions, and
      that this effect is not due to retinal afterimages.

PMID- 20677700
TI  - Natural visual-field features enhance vection.
AB  - When a large optic-flow pattern is viewed, induced self-motion perception
      (vection) can result even for observers who are stationary relative to Earth.
      Vection is common in optokinetic drums, large-screen cinemas, vehicle simulators,
      and other virtual environments. However, not all optic-flow patterns are equally
      effective in producing vection. We hypothesized that visual-field characteristics
      that typically accompany self-motion are likely to facilitate vection. The two
      characteristics tested in the current study were color and global visual-field
      movement consistent with head bob and sway that occurs when a person walks or
      runs. Stationary observers viewed first-person perspective video clips on a rear
      projection screen that depicted forward self-motion. Vection onset and magnitude
      were measured with a computer-interfaced slide device. In experiment 1, either a
      grayscale or color video was presented. In experiment 2, the video was shot
      either from a smooth rolling cart or with a hand-held camera that yielded gait
      information in addition to global expansion. Vection onset was found to be
      faster, and stronger in magnitude, when videos containing color and gait
      movements were viewed. These results suggest that visual-field features that are
      common during actual self-motion can enhance vection in a virtual environment,
      resulting in a more realistic experience for viewers.

PMID- 20677701
TI  - Shape, gravity, and the perception of the right angle.
AB  - Past efforts to determine whether orientation-dependent sensitivity to right
      angles is due to retinal or environmental/gravitational frames of reference have
      produced conflicting conclusions. I attempt to show that the chief factor
      underlying this phenomenon is, rather, the shape of the object containing the
      angle. This shape mediates the typical orientation of the object in a ground-
      gravity context and the consequent force-structure of the incorporated angle-a
      force structure that is reflected in the percept.

PMID- 20677702
TI  - Role of a texture gradient in the perception of relative size.
AB  - Two theories regarding the role of a texture gradient in the perception of the
      relative size of objects are compared. Relational theory states that relative
      size is directly specified by the projective ratio of the numbers of texture
      elements spanned by objects. Distance calibration theory assumes that relative
      size is a product of visual angle and distance, once the distance is specified by
      the texture. Experiment 1 involved three variables: background (no texture,
      texture gradient patterns), the ratio of heights of the comparison stimulus to a
      standard (three levels), and angular vertical separation of the standard stimulus
      below the horizon (two levels). The effect of the retinal length of the
      comparison stimulus was examined in experiment 2. In both experiments,
      participants judged both the apparent size and distance of a comparison stimulus
      relative to a standard stimulus. Results suggest that the cues selected by
      observers to judge relative size were to some degree different from those used to
      judge relative distance. Relative size was strongly affected by a texture
      gradient and the retinal length of a comparison stimulus whereas relative
      distance perception was affected by relative height. When dominant cues that
      specify size are different from those which specify distance, relational theory
      might provide a better account of relative size perception than distance
      calibration theory.

PMID- 20677703
TI  - The development of locomotor planning for end-state comfort.
AB  - Walking through real-world environments involves using perceptual information to
      make complex choices between alternative routes, and this ability must develop
      through childhood. We examined performance and its development in one such
      situation. We used a novel 'river-crossing' paradigm analogous to manual 'end
      state comfort' planning tasks, where an uncomfortable manoeuvre at the start of a
      movement is traded off for comfort at its end. Adults showed locomotor end-state
      comfort planning, adjusting feet at the start of a route in order to gain comfort
      at its end (crossing a manageable gap between two stepping stones). 3-6-year-olds
      also made this trade-off, but to a lesser degree than adults. The results suggest
      that end-state comfort is an important determiner of locomotor behaviour.
      Furthermore, they show that children as young as 3 years can use detailed visual
      information to form sophisticated locomotor plans.

PMID- 20677704
TI  - Dynamic phenomenology of grapheme-color synesthesia.
AB  - In grapheme-color synesthesia, observers perceive colors that are associated with
      letters and numbers. We tested the dynamic limits of this phenomenon by exposing
      two synesthetes to characters that rotate smoothly, that morph into other
      characters, that disappear abruptly, or that have colors either consistent or
      inconsistent with the corresponding synesthetic color. Rotating letters changed
      their synesthetic colors abruptly as letter identification changed or failed.
      Morphing letters also changed color together with a change in letter
      identification. Abrupt disappearance of a black character on a white background
      yielded a negative afterimage, but maintenance of the same synesthetic color. Our
      synesthetes could maintain both physical and synesthetic color in the same
      character, without conflict. Neon color spreading in one observer occurred for
      physical but not synesthetic color. These and other results show close linking of
      synesthetic color with character identity rather than image properties, in
      contrast to physical color.

PMID- 20677705
TI  - A classification of perceptual corrections of perspective distortions in
      renaissance painting.
AB  - In an attempt to address major debates in perspective studies, this study brings
      perceptual research to bear on the problem of the status of perspective in the
      Renaissance. Between one school that sees perspective as mathematically rigorous
      but imperfectly applied and another that regards perspective as an incoherent
      discipline, this study argues that errors in the use of perspective are
      consistent and can be classified into two tendencies: first, the tendency to
      normalize a foreshortened form towards frontality and, second, the tendency to
      flatten a three-dimensional object to reveal its hidden sides. These tendencies
      find confirmation both in the Renaissance doctrine of the judgment of the eye
      (giudizio dell'occhio) as well as in Gestalt-oriented perceptual research.
      Numerous examples of their application are given with regard to the
      representation of human figures, architecture, and the relation of figures to
      space.

PMID- 20677706
TI  - Perceptual overestimation of rising intensity: is stimulus continuity necessary?
AB  - A "perceptual bias for rising intensity" (Neuhoff 1998, Nature 395 123-124) is
      not dependent on the continuous change of a dynamic, looming sound source. Thirty
      participants were presented with pairs of 500 ms steady-state sounds
      corresponding to onset and offset levels of previously used dynamic increasing-
      and decreasing-intensity stimuli. Independent variables, intensity-change
      direction (increasing, decreasing), intensity region (high: 70-90 dB SPL, low: 50
      70 dB SPL), interstimulus interval (ISI) (0 s, 1.8 s, 3.6 s), and timbre (vowel,
      violin) were manipulated as a fully within-subjects design. The dependent
      variable was perceived loudness change between each stimulus item in a pair. It
      was hypothesised that (i) noncontinuous increases of intensity are overestimated
      in loudness change, relative to decreases, in both low-intensity and high
      intensity regions; and (ii) perceptual overestimation does not occur when end
      levels are balanced. The hypotheses were partially supported. At the high
      intensity region, increasing stimuli were perceived to change more in loudness
      than decreasing-intensity stimuli. At the low-intensity region and under balanced
      end-level conditions, decreasing-intensity stimuli were perceived to change more
      in loudness than increasing-intensity stimuli. A significant direction x region
      interaction varied as a function of ISI. Methodological, sensory, and cognitive
      explanations for overestimation in certain circumstances are discussed.

PMID- 20677707
TI  - Ternus effect: two processes or differential activation? Comments on Odic and
      Pratt's 2008 paper.
AB  - Using a bistable apparent-motion display, Odic and Pratt (2008, Perception 37
      1790-1804) have recently presented data that they interpret as being inconsistent
      with what they call "the two-process theory". Instead, they argue, their data can
      be explained by the differential-activation theory along with a process they
      identify as "temporal summation of contrast". It is argued here that Odic and
      Pratt misinterpreted the two-process distinction and used a display that was too
      unusual to be adequately addressed by it. Further, their use of the differential
      activation theory and, in particular, the temporal summation of contrast, seems
      problematic. It is concluded that there is little in their data and theoretical
      interpretation to justify rejection of the two-process approach.

PMID- 20677709
TI  - Higher prevalence of synaesthesia in art students.
AB  - Synaesthesia may facilitate the expression of creativity. Therefore synaesthetes
      may be more common in the world of creative art. To test this possibility, we
      used behavioural and phenomenological measures to assess the existence of
      grapheme-colour synaesthesia in a sample of art students (N = 99) and a control
      sample (N = 96). We found a prevalence of about 7% in the former and about 2% in
      the latter. Our findings suggest that synaesthesia may indeed be more common in
      art students.

PMID- 20677710
TI  - The 'rotating snakes' in smooth motion do not appear to rotate.
AB  - 'Rotating snakes' is an illusory figure in which the 'snakes' are perceived to
      rotate. We report that when the image moves smoothly, the snakes do not appear to
      rotate, although the retinal images are continuously refreshed. Therefore, to
      produce the illusion, the image should remain stationary (without being
      refreshed) for some time on the same retinal position.

PMID- 20677711
TI  - DNR? DDN? TLA?

PMID- 20677716
TI  - Nurses' and therapists' experiences with occupational musculoskeletal injuries.

PMID- 20677717
TI  - Shingles.
AB  - Shingles, an acute infection of the nervous system, and postherpetic neuralgia
      (PHN), a painful complication of zoster that can prolong recovery, are likely to
      be seen more frequently in the U.S. workplace as the population ages and as
      workers return to the workplace in immunocompromised states (e.g., with AIDS,
      after treatment for cancer, and after organ transplantation). Shingles and PHN
      could adversely affect productivity and lead to absenteeism. Zostavax is a new
      vaccine effective for preventing shingles and PHN. Occupational health nurses can
      recognize potential cases of shingles and refer for treatment early. Occupational
      health nurses are also in a position to establish vaccination campaigns or to
      recommend vaccinations to employees. It is anticipated that early intervention
      and prevention of shingles could reduce absenteeism, improve productivity in the
      workplace, and significantly improve quality of life for the aging work force.

PMID- 20677718
TI  - You're a published author!
AB  - Once a nurse author writes a quality manuscript, the article is submitted to an
      appropriate journal, reviewed by the editor, and sent to review panel members
      with expertise consistent with the topic of the article or the methodology of
      research articles. After review, panel members recommend the article be
      published, accepted for publication after revision, revised without promise of
      publication, or rejected. Nurse authors have options as to how they handle the
      recommendation. To successfully publish in a peer-reviewed journal, nurse authors
      should communicate with the editor and realize that the editor and author have
      the same goals.

PMID- 20677719
TI  - A clinical ladder for occupational health nurses.
AB  - Occupational health nurses must have a growing, expanding knowledge base to
      remain current in practice. The American Board for Occupational Health Nurses,
      Inc. encourages advancement with the availability of certification examinations.
      Health care centers support clinical advancement programs for bedside nurses.
      Nurses who continue their education either through a degree program or via
      continuing education or certification advance up the clinical ladder, receiving a
      higher salary, recognition from their peers, and perhaps even financial
      assistance to continue climbing, yet occupational health nurses do not have their
      own clinical advancement ladder. This article examines the steps necessary to
      develop a clinical ladder and presents a clinical ladder specific to occupational
      health nursing developed by the author.

PMID- 20677722
TI  - Nurses' ratings of their health and professional work environments.
AB  - Interactions between nursing work environments and nurses' health are of growing
      significance, given the aging work force, nursing shortage, and workplace health
      risks. This study examined relationships among nurses' ratings of health
      behaviors, health status, and professional work environments. Registered nurses
      (N = 3,132) from five multi-state settings completed an electronic survey.
      Participants' general health ratings were good, yet stress levels remained the
      one consistent predictor of poorer health ratings and work environment ratings in
      regression models. Additionally, more than half of the participants reported
      being overweight, only 50% met physical activity standards, more than two thirds
      reported a history of back or needlestick injuries, and 44% and 62% reported
      experiencing verbal abuse by colleagues and patients, respectively. Contrary to
      other studies, professional work environment as measured in this study did not
      predict nurses' health ratings. Further study of the impact of stress on long
      term health outcomes and work force retention, as well as on worksite health
      strategies, is needed.

PMID- 20677720
TI  - Health coaching: a fresh approach for improving health outcomes and reducing
      costs.
AB  - Health coaching is a fresh approach for occupational health nurses that improves
      health outcomes and reduces costs by engaging individuals to change unhealthy
      behaviors. This article explores how health coaching works, how it affects
      compliance, and why traditional approaches have fallen short.

PMID- 20677723
TI  - Panic attacks.
AB  - Panic attack symptoms mimic other serious health problems and have implications
      for the occupational health nurse. In the workplace, the results of panic
      disorder may lead to poor job performance and affect the morale and effectiveness
      of the entire workplace.

PMID- 20677725
TI  - Pentacam equivalent K-reading.

PMID- 20677726
TI  - A prospective randomized comparison of four femtosecond LASIK flap thicknesses.
AB  - PURPOSE: To evaluate the visual outcomes, predictability, and planarity of four
      types of 60-kHz femtosecond laser-assisted LASIK flaps: 90, 100, 110, and 120
      microm. METHODS: This randomized, prospective, interventional, comparative trial
      was performed at a tertiary care facility. Two hundred forty eyes with a
      calculated residual bed thickness >300 microm (at 120-microm flap thickness and
      subjective refraction) were randomized into four flap thickness groups to undergo
      femtosecond laser-assisted LASIK. Pre- and postoperative assessment included
      uncorrected visual acuity, best spectacle-corrected visual acuity (BSCVA), and
      refraction. Flap thickness was assessed by anterior segment optical coherence
      tomography on 28 points per flap at 1-month follow-up. Three new indices were
      devised to assess the predictability and planarity. RESULTS: The baseline
      parameters were matched. Postoperative vision and refractive outcome were similar
      in the four groups (P>.05, analysis of variance). The achieved flap thickness was
      different at each measured point among the groups (P<.05) with standard
      deviations ranging from +/-3.2 to +/-7.3 microm. The predictability and planarity
      were satisfactory in all four groups, although the indices were slightly better
      in the 110-microm and 120-microm groups. No loss of BSCVA or flap complications
      occurred in the four groups. CONCLUSIONS: The study demonstrated that all four
      flap thicknesses are relatively uniform in predictability and clinical outcomes.

PMID- 20677727
TI  - Anterior segment optical coherence tomography measurement of flap thickness after
      myopic LASIK using the Moria one use-plus microkeratome.
AB  - PURPOSE: To analyze the accuracy and consistency of corneal flap thickness
      created in myopic LASIK using the Moria One Use-Plus microkeratome compared with
      the Moria M2 Single Use 90-microm microkeratome. METHODS: Bilateral LASIK was
      performed in 68 myopic patients. Flaps were created using the One Use-Plus
      microkeratome in 82 eyes (41 patients) and the M2 90-microm microkeratome in 54
      eyes (27 patients). Flap complications and visual outcomes were evaluated.
      Horizontal "High Res. Corneal" scan pattern of anterior segment optical coherence
      tomography (AS-OCT) was applied to measure flap thickness at five locations (0,
      +/-2, and +/-3.5 mm from the corneal vertex) on the first postoperative day.
      RESULTS: No significant differences were noted in flap complications and visual
      outcomes between groups. The central flap thickness was dramatically thinner in
      the One Use-Plus group (114.7+/-10.1 microm and 109.4+/-11.0 microm for right and
      left eyes, respectively) than in the M2 group (155.6+/-14.8 microm and 151.6+/
      12.5 microm for right and left eyes, respectively) (P<.001). The One Use-Plus did
      not show a markedly better uniformity than the M2; the variation was mainly
      observed in the periphery. Multiple linear regression showed that for the One Use
      Plus, the steeper the preoperative keratometry, the thicker the flap thickness,
      and for the M2, the thicker the preoperative pachymetry, the thicker the flap
      (P<.1). CONCLUSIONS: The One Use-Plus and M2 microkeratomes have similar safety
      and efficacy. The flap created by the One Use-Plus was much thinner than the flap
      created with the M2; however, the One Use-Plus can not realize a fully planar
      shaped flap.

PMID- 20677728
TI  - High and low contrast visual acuity after artiflex phakic intraocular lens
      implantation for the correction of myopia.
AB  - PURPOSE: To determine the effects of Artiflex phakic intraocular lens (PIOL)
      implantation on best spectacle-corrected high and low contrast visual acuity
      under photopic and mesopic conditions. METHODS: Forty-two consecutive eyes had
      implantation of a foldable iris-supported PIOL to correct myopia. The mean
      preoperative spherical equivalent refraction was -7.26+/-1.91 diopters (D)
      (range: -4.90 to -13.60 D). The high (100%) and low (2.5%) contrast visual acuity
      with best spectacle correction was tested with translucent logarithmic visual
      acuity charts (Precision Vision) under photopic and mesopic conditions. RESULTS:
      At mean 7.6+/-5.4 months after PIOL implantation, the mean high and low contrast
      visual acuity under photopic and mesopic conditions had significantly increased
      from preoperatively: photopic high contrast visual acuity from -0.07+/-0.11
      logMAR to -0.14+/-0.08 logMAR (P<.001); photopic low contrast visual acuity from
      0.48+/-0.14 logMAR to 0.36+/-0.11 logMAR (P=.011); mesopic high contrast visual
      acuity from -0.09+/-0.09 logMAR to -0.16+/-0.08 logMAR (P<.001); and mesopic low
      contrast visual acuity from 0.50+/-0.13 logMAR to 0.33+/-0.10 logMAR (P<.001).
      Mean postoperative spherical equivalent refraction was -0.21+/-0.28 D (range:
      +0.50 to -0.75 D). Of all eyes, 91.9% were within 0.50 D of attempted correction,
      and 67% gained 1 or more lines of best spectacle-corrected visual acuity (BSCVA).
      No eye lost 2 or more lines of BSCVA. CONCLUSIONS: Artiflex PIOL implantation for
      the correction of moderate to high myopia seems to be a safe and predictable
      procedure, which resulted in increased high and low contrast visual acuity under
      photopic and mesopic conditions.

PMID- 20677729
TI  - An intraocular lens power calculation formula based on optical coherence
      tomography: a pilot study.
AB  - PURPOSE: To develop an intraocular lens (IOL) power calculation formula based on
      optical coherence tomography (OCT) that would not be biased by previous laser
      vision correction. METHODS: Twenty-seven eyes of 27 cataract patients without
      prior laser vision correction who underwent phacoemulsification were included in
      the study. An optical coherence biometer (IOLMaster, Carl Zeiss Meditec) measured
      anterior corneal curvature and axial eye length. A high-speed (2000 Hz) anterior
      segment OCT prototype mapped corneal thickness and measured anterior chamber
      depth and crystalline lens thickness. Posterior corneal curvature was computed by
      combining IOLMaster keratometry with OCT corneal thickness mapping. A new IOL
      formula was developed based on these parameters. One month after
      phacoemulsification, the manifest refraction spherical equivalent (MRSE) was
      measured. The prediction error in postoperative MRSE of the OCT-based IOL formula
      was compared with that of three theoretic formulae: SRK/T, Hoffer Q, and Holladay
      II. RESULTS: The mean prediction error in postoperative MRSE of the OCT-based
      formula was 0.04+/-0.44 diopters (D). The SRK/T was the best of the theoretic
      formulae, and its prediction error was -0.35+/-0.42 D. Twenty-one (78%) eyes were
      within 0.50 D using the OCT formula compared to 18 (67%) eyes using the SRK/T. No
      statistically significant differences were noted among the formulae. CONCLUSIONS:
      For cataract patients without prior laser vision correction, the OCT-based IOL
      formula was as accurate as the current theoretic formulae. This new formula is
      based on direct OCT assessment of the posterior curvature and avoids the
      calculation errors inherent in conventional IOL formulae.

PMID- 20677730
TI  - Development of a new subjective questionnaire: the Freedom from Glasses Value
      Scale (FGVS).
AB  - PURPOSE: To develop a patient self-administered questionnaire assessing the added
      value of complete independence from spectacles (hereafter referred to as glasses)
      after multifocal intraocular lens (IOL) surgery. METHODS: Exploratory interviews
      with five cataract patients and six presbyopic patients with AcrySof ReSTOR IOLs
      (Alcon Laboratories Inc) implanted in both eyes for at least 6 months were
      conducted. The questionnaire's conceptual framework was developed after interview
      analysis. Based on the identified concepts, items were generated simultaneously
      in French and Spanish using patients' own words, and comprehension tested with
      six French patients; the Spanish questionnaire underwent clinician review and was
      further tested with four Spanish patients. French and Spanish versions were
      accordingly refined. The questionnaire was linguistically validated in UK English
      and Danish. RESULTS: Interview analysis resulted in the identification of 9
      global concepts: global vision, practical constraints related to wearing glasses,
      impact of eye surgery on the patient's life, improvement of practical issues
      without glasses, improvement of psychological constraints without glasses,
      physical appearance/aesthetic aspect, self-image and in the eyes of others,
      eyesight problems left behind after surgery, and recommendation of surgery to
      others. The initial version of the test questionnaire contained 23 items; 2 items
      were deleted and changes were made after clinician review and patient testing.
      The final questionnaire named Freedom from Glasses Value Scale (FGVS) contained
      21 items and four general additional questions. CONCLUSIONS: Beyond functional
      aspects, this qualitative study identified additional benefits in cataract and
      presbyopic patients living free of glasses after receiving multifocal IOLs. The
      FGVS now needs to be psychometrically validated (eg, construct validity and
      reliability).

PMID- 20677731
TI  - Traumatic dislocation of LASIK flaps 4 and 9 years after surgery.
AB  - PURPOSE: To report two patients who developed a corneal flap dehiscence 4 years
      and 9 years after LASIK, respectively, following trauma during routine domestic
      activities. METHODS: Retrospective chart review of two patients. Clinical
      presentation, mechanism of injury, treatment, complications, and outcome were
      studied. A review of published cases in the English literature on late onset flap
      dislocation was performed. RESULTS: Case 1 involved a 30-year-old man who
      presented 4 years after LASIK, after his eye was struck with a piece of wood from
      a window trim. Examination showed uncorrected visual acuity (UCVA) of 20/25 and
      flap displacement, creating a fold at the superior edge. Because the injury
      involved the periphery of the flap, the patient was treated medically only. Final
      UCVA was 20/20(-1) with a persistent fold. Case 2 involved a 29-year-old man who
      dislocated his flap after being hit with a dog's paw 9 years after LASIK.
      Uncorrected visual acuity was count fingers, and a complete flap dislocation that
      was folded at the hinge with 30% epithelial ingrowth was noted. Immediate
      surgical removal of the epithelium from the stromal bed was completed and a
      bandage contact lens was used along with topical medication. Final UCVA was
      20/25, with no complications. CONCLUSIONS: Flap dehiscence is a rare, late
      complication of LASIK. Case 1 is the second report of flap dislocation treated
      medically only and case 2 is the latest report. Tangential force applied to the
      flap during routine activities of life can result in flap displacement for up to
      9 years after LASIK.

PMID- 20677732
TI  - Quantum chemical studies of proton-coupled electron transfer in metalloenzymes.

PMID- 20677733
TI  - Asprich peptides are occluded in calcite and permanently disorder biomineral
      crystals.
AB  - Macromolecules are a minority but important component of the minerals formed by
      living organisms, or biominerals. The role these macromolecules play at the early
      stages of biomineral formation, as well as their long-term and long-range effects
      on the mature biomineral, is poorly understood. A 42-amino acid peptide, asp2,
      was derived from the Asprich family of proteins. In this study we present X-ray
      absorption near-edge structure spectroscopy and X-ray photoelectron emission
      microscopy data from the asp2 peptide, the calcite (CaCO(3)) crystals, and the
      peptide + crystal composites. The results clearly show that asp2 is occluded in
      fully formed biomineral crystals and slightly but permanently disorders the
      crystal structure at short- and long-range distances.

PMID- 20677734
TI  - Kinetics of the hydrolysis of atmospherically relevant isoprene-derived hydroxy
      epoxides.
AB  - Isoprene (the most abundant nonmethane hydrocarbon emitted into the atmosphere)
      is known to undergo oxidation to 2-methyl-1,2,3,4-butanetetraol, a hydrophilic
      compound present in secondary organic aerosol (SOA) in the atmosphere. Recent
      laboratory work has shown that gas phase hydroxy epoxides are produced in the low
      NOx photooxidation of isoprene and that these epoxides are likely to undergo
      efficient acid-catalyzed hydrolysis on SOA to 2-methyl-1,2,3,4-butanetetraol at
      typical SOA acidities. In order to confirm this hypothesis, the specific hydroxy
      epoxides observed in the isoprene photooxidation experiment (as well as several
      other related species) were synthesized, and the hydrolysis kinetics of all
      species were studied via nuclear magnetic resonance (NMR) techniques. It was
      determined that the isoprene-derived hydroxy epoxides should undergo efficient
      hydrolysis under atmospheric conditions, particular on lower pH SOA. An empirical
      structure-reactivity model was constructed that parametrized the hydrolysis rate
      constants according to the carbon substitution pattern on the epoxide ring and
      number of neighboring hydroxy functional groups. Compared to the previously
      studied similar nonfunctionalized epoxides, the presence of a hydroxy group at
      the alpha position to the epoxy group was found to reduce the hydrolysis rate
      constant by a factor of 20, and the presence of a hydroxy group at the beta
      position to the epoxy group was found to reduce the hydrolysis rate constant by a
      factor of 6.

PMID- 20677735
TI  - Directing the formation of nanostructured rings via local oxidation.
AB  - We provide compelling evidence that ring formation in solutions of thiol
      passivated Au nanoparticles is driven by breath figure dynamics. A method for the
      controlled placement of rings of nanoparticles on a solid substrate, which
      exploits variations in substrate wettability to fix the positions of the
      submicrometer water droplets formed in the breath figure process, has been
      developed. This is achieved by heterogeneously patterning hydrogen-terminated
      silicon substrates with oxide regions that act as adsorption sites for the
      droplets. The droplets in turn template the formation of thiol-passivated Au
      nanoparticle rings during spin-casting from volatile solvents.

PMID- 20677736
TI  - Can simple salts influence self-assembly in oil? Multivalent cations as efficient
      gelators of lecithin organosols.
AB  - It is known that lecithin, a zwitterionic phospholipid, self-assembles into
      spherical reverse micelles in organic solvents. We have explored the effects of
      adding inorganic salts to lecithin organosols. Salts are insoluble in organic
      solvents, and hence their effects on reverse self-assembly have rarely been
      studied. Our studies show, however, that salts can indeed be dissolved in organic
      liquids in the presence of lecithin. More interestingly, salts of multivalent
      cations like calcium (Ca(2+)), magnesium (Mg(2+)), lanthanum (La(3+)), and cerium
      (Ce(3+)) greatly increase the viscosity of lecithin organosols and transform the
      samples into optically transparent organogels. In comparison, monovalent cations
      or transition-metal cations have negligible effect on reverse self-assembly. On
      the basis of data from small-angle neutron scattering (SANS), we show that
      gelation is accompanied by a nanostructural transition from spherical micelles to
      cylindrical micelles/filaments. The varying abilities of different cations to
      induce gelation is shown to correlate with their binding tendencies to the
      phosphocholine headgroups of lecithin. A two-component gelator such as
      lecithin/Ca(2+) could be attractive for applications due to its negligible cost
      and nontoxic nature. We demonstrate how such a gelator combination can convert a
      liquid fuel such as kerosene into a gel without the use of heat or shear. The
      same gel can also further be ungelled by addition of a few drops of alcohol.

PMID- 20677737
TI  - Resveratrol and its oligomers from wine grapes are selective (1)O2 quenchers:
      mechanistic implication by high-performance liquid chromatography-electrospray
      ionization-tandem mass spectrometry and theoretical calculation.
AB  - Resveratrol and its oligomers, abundantly present in wine grapes, are believed to
      be effective phytoalexins for the phenomenon "French paradox" partially by virtue
      of their powerful antiradical properties. EPR spin-trapping technique was
      utilized, demonstrating all polyphenols were selective (1)O2 quenchers but not
      effective (*)OH and O2(*-) scavengers. On the basis of the HPLC-ESI-MS(2)
      analysis for the simulated reactions of polyphenols with (1)O2, the molecular
      weights of the resulting photochemical products were 14 or 28 Da higher than
      those of their substrates. No fragment C2H2O (42 Da), which was rather
      distinctive of the resorcinol rings in these cases, had been observed, whereas
      their MS/MS spectra displayed characteristic neutral fragments including carbon
      monoxide (CO, 28 Da) and 2-hydroxy[1,4]benzoquinone (C6H4O3, 124 Da). Finally,
      PM3 semiempirical calculations and HR-FTICR-MS experiments were performed,
      supporting the assertion that their quenching mechanism involved physical and
      chemical pathways. Chemical quenching underwent an endoperoxide intermediate form
      to generate quinones.

PMID- 20677738
TI  - Pore-scale analysis of evaporation and condensation dynamics in porous media.
AB  - We developed analytical models for surface- and capillary-assisted condensation
      and evaporation dynamics considering phase-change behavior in idealized wedge
      shaped pores and in adsorbed liquid films as building blocks for condensation and
      evaporation in granular media. Phase-change rates are important for dust
      mobilization and deposition, vapor transport through partially saturated media,
      and for residence times of emitted combustion particulates. The basic wedge-film
      solution was scaled up to represent 3D transient evaporation and condensation
      processes within an assembly of rough spherical particles. Model comparisons with
      experimental data for evaporation from a single meniscus and condensation rates
      into sand samples show consistent agreement for a range of media and ambient
      conditions.

PMID- 20677739
TI  - Solution behavior of poly(sodium(sulfamate-carboxylate)isoprene), a pH sensitive
      and intrinsically hydrophobic polyelectrolyte.
AB  - The solution properties of a novel pH sensitive and intrinsically hydrophobic
      polyelectrolyte poly(sodium(sulfamate-carboxylate)isoprene) (SCPI) were
      investigated by means of dynamic, static, and electrophoretic light-scattering
      and fluorescence spectroscopy techniques. Because of the pH dependent charge
      density of the polyelectrolyte chain, the dynamics and structure of the solution
      were studied at both pH 7 (high charge density) and pH 3 (low charge density) and
      at low ionic strength conditions for two samples of different molecular weights.
      In all cases, a fast and a slow diffusive mode were observed. The fast mode is
      attributed to the diffusion of isolated polyelectrolyte chains, while the slow
      mode denotes the presence of multichain domains in solution, formed by
      electrostatic and/or hydrophobic interactions. The size and density of the
      multichain domains were reduced with decreasing charge density and molecular
      weight. Effective charge of the particles does not depend appreciably on solution
      pH, while fluorescence spectroscopy revealed the presence of hydrophobic domains
      in the studied systems. It was found that increasing temperature resulted in the
      compaction of both isolated chains and multichain domains due to the hydrophobic
      effect. Furthermore the increase of the ionic strength of the solution led to a
      partial dissociation of the multichain domains at short times and at pH 7, while
      it led to increased aggregation and precipitation at pH 3 and long times. The
      performed experiments allowed for a separation of the electrostatic and
      hydrophobic contributions to the self-assembly of the particular polyelectrolyte
      systems.

PMID- 20677740
TI  - Trends in European background air reflect reductions in primary emissions of PCBs
      and PBDEs.
AB  - Data are presented for polychlorinated biphenyls (PCBs) and polybrominated
      diphenyls ethers (PBDEs) in passive air samplers (PAS) collected along a
      rural/remote latitudinal transect from southern UK to northern Norway during 2004
      2008. This study is part of an ongoing campaign, using semipermeable membrane
      devices (SPMDs) as PAS over two year intervals since 1994. Absolute sequestered
      amounts of selected PCB congeners have decreased in a first order fashion between
      1994-2008, with the average time of 8.4+/-3.2 years for atmospheric
      concentrations to decline by 50%. PCBs have continued to fractionate with
      latitude during this period. PBDE concentrations declined by 50% between 2000 and
      2008 every 2.2+/-0.4 years. Results are discussed in terms of sources, long-range
      atmospheric transport, global fractionation, and clearance processes. It is
      concluded that the spatial and temporal trends in background European air mainly
      reflect the strength of primary diffusive emissions of these compounds and
      subsequently their ongoing declines. The direct evidence for this is similar
      rates of decline at all the sites; similar rates of decline for all congeners; no
      systematic change in the fractionation pattern since 1994. The latest results
      indicate a reduction in the rate of decline for PCBs (and hence in primary
      emissions).

PMID- 20677741
TI  - Mechanistic category formation for the prediction of respiratory sensitization.
AB  - This study investigates the ability of a set of previously published rules for
      protein binding, developed from skin sensitization data, to group chemicals into
      mechanistic domains and to develop knowledge on the chemical interactions
      relating to respiratory sensitization. The results of the analysis showed that 32
      of 39 respiratory sensitizing chemicals could be assigned to a mechanistic domain
      based on the published rules. Analysis of the remaining six chemicals showed them
      to have electrophilic mechanisms that had not been explicitly covered by the skin
      sensitization protein binding rules. The study also highlighted the ability to
      develop subdomains within the mechanistic domains on the basis of simple
      chemistry principles. These subdomains were developed to allow a calculated
      electrophilic index to rationalize the differing respiratory sensitizing
      potentials of the chemicals assigned to them. The study clearly highlights how
      assigning the most likely mechanism of action for a chemical is useful in
      building chemical categories (domains) and subcategories (subdomains).

PMID- 20677742
TI  - Free energy perturbation simulation on transition states and high-activity
      mutants of human butyrylcholinesterase for (-)-cocaine hydrolysis.
AB  - A unified computational approach based on free energy perturbation (FEP)
      simulations of transition states has been employed to calculate the mutation
      caused shifts of the free energy change from the free enzyme to the rate
      determining transition state for (-)-cocaine hydrolysis catalyzed by the
      currently most promising series of mutants of human butyrylcholinesterase (BChE)
      that contain the A199S/A328W/Y332G mutations. The FEP simulations were followed
      by Michaelis-Menten kinetics analysis determining the individual k(cat) and K(M)
      values missing for the A199S/F227A/A328W/Y332G mutant in this series. The
      calculated mutation-caused shifts of the free energy change from the free enzyme
      to the rate-determining transition state are in good agreement with the
      experimental kinetic data, demonstrating that the unified computational approach
      based on the FEP simulations of the transition states may be valuable for future
      computational design of new BChE mutants with a further improved catalytic
      efficiency against (-)-cocaine.

PMID- 20677743
TI  - Gold nanoparticle enrichment method for identifying S-nitrosylation and S
      glutathionylation sites in proteins.
AB  - We present a simple method by which gold nanoparticles (AuNPs) are used to
      simultaneously isolate and enrich for free or modified thiol-containing peptides,
      thus facilitating the identification of protein S-modification sites. Here,
      protein disulfide isomerase (PDI) and dual specificity phosphatase 12 (DUSP12 or
      hYVH1) were S-nitrosylated or S-glutathionylated, their free thiols
      differentially alkylated, and subjected to proteolysis. AuNPs were added to the
      digests, and the AuNP-bound peptides were isolated by centrifugation and released
      by thiol exchange. These AuNP-bound peptides were analyzed by MALDI-TOF mass
      spectrometry revealing that AuNPs result in a significant enrichment of free
      thiol-containing as well as S-nitrosylated, S-glutathionylated, and S-alkylated
      peptides, leading to the unequivocal assignment of thiols susceptible to
      modification.

PMID- 20677744
TI  - Capillary force induced formation of monodisperse polystyrene/silica organic
      inorganic hybrid hollow spheres.
AB  - This paper presents a "one-spot" procedure to fabricate polystyrene/silica
      (PS/SiO(2)) hybrid hollow spheres. In this approach, when poly(vinylpyrrolidone)
      stabilized PS colloids were deposited by sol-gel derived silica layer under
      acidic medium, it was interesting to find that the PS/SiO(2) core-shell colloids
      gradually changed to hollow structure spontaneously in the same medium as
      reaction went on. The formation of this hollow structure should be attributed to
      the diffusion of PS macromolecular chains from core particles into the voids
      between silica nanoparticles driven by the strong capillary force.

PMID- 20677745
TI  - A covalent succinylcysteine-like intermediate in the enzyme-catalyzed
      transformation of maleate to fumarate by maleate isomerase.
AB  - Maleate isomerase (MI), a member of the Asp/Glu racemase superfamily, catalyzes
      cis-trans isomerization of the C2-C3 double bond in maleate to yield fumarate.
      Mutational studies, in conjunction with the structure of the C194A mutant of
      Nocardia farcinica MI cocrystallized with maleate, have revealed an unprecedented
      mode of catalysis for the superfamily in which the isomerization reaction is
      initiated by nucleophilic attack of cysteine at the double bond, yielding a
      covalent succinylcysteine-like intermediate.

PMID- 20677746
TI  - Fluorescence lifetime analysis and fluorescence correlation spectroscopy
      elucidate the internal architecture of fluorescent silica nanoparticles.
AB  - Fluorescence lifetime (FL) analysis and fluorescence correlation spectroscopy
      (FCS) have been successfully employed to reveal detailed information about the
      internal architecture of fluorescent silica nanoparticles (NPs). The dual
      component lifetime behavior shows a two-domain dye distribution in the NP as a
      function of solvent accessibility. The introduction of an undoped silica shell
      serves to stabilize the outer dye fraction that is manifest as an increase in
      lifetime. The FCS not only shows a size-dependent increase in the cross
      correlation decay constant but also demonstrates a significant relaxation in the
      FCS signal with the introduction of an undoped silica shell.

PMID- 20677747
TI  - Emulsion polymerization routes to chemically anisotropic particles.
AB  - Methods are presented to synthesize suspensions of chemically and shape
      anisotropic colloids on submicrometer length scales. Particles are synthesized
      through seeded emulsion polymerization where a weakly cross-linked seed is
      swollen with monomer that phase separates at the reaction temperature resulting
      in a protrusion. The final particles can be considered to be composed of
      interpenetrating spheres. pH-sensitive anisotropy is created through the use of
      different surface coatings on each of the interpenetrating spheres. Dark-field
      imaging, dynamic light scattering, and scanning electron microscopy are used to
      characterize the particles.

PMID- 20677748
TI  - Orthogonal covalent and noncovalent functionalization of cyclodextrin-alkyne
      patterned surfaces.
AB  - The creation of cyclodextrin patterns on a fluorescent reporter surface by
      microcontact printing provides a versatile orthogonal surface modification
      method. The alkyne-beta-cyclodextrin surface is prepared through a "click"
      reaction on alkyne-terminated coumarin monolayers. The resulting alkyne-beta
      cyclodextrin surface can be functionalized through supramolecular microcontact
      printing on cyclodextrin host patterns and by reactive microcontact printing
      induced click chemistry on the alkyne-terminated patterns. The orthogonal
      covalent and supramolecular "host-guest" functionalization of the surface, and
      its specificity as well as selectivity, is demonstrated by sequential and one
      step printing procedures.

PMID- 20677749
TI  - Boronic acids and esters in the Petasis-borono Mannich multicomponent reaction.

PMID- 20677750
TI  - Indacenodithiophene semiconducting polymers for high-performance, air-stable
      transistors.
AB  - High-performance, solution-processed transistors fabricated from semiconducting
      polymers containing indacenodithiohene repeat units are described. The bridging
      functions on the backbone contribute to suppressing large-scale crystallization
      in thin films. However, charge carrier mobilities of up to 1 cm(2)/(V s) for a
      benzothiadiazole copolymer were reported and, coupled with both ambient stability
      and long-wavelength absorption, make this family of polymers particularly
      attractive for application in next-generation organic optoelectronics.

PMID- 20677751
TI  - Boryltrihydroborate: synthesis, structure, and reactivity as a reductant in
      ionic, organometallic, and radical reactions.
AB  - Reaction of lithium 1,3-bis(2,6-diisopropylphenyl)-2,3-dihydro-1H-1,3,2
      diazaborol-2-ide with borane.THF provides the first boryl-substituted
      borohydride: lithium [1,3-bis(2,6-diisopropylphenyl)-2,3-dihydro-1H-1,3,2
      diazaborol-2-yl]trihydroborate. The compound is fully characterized by (11)B,
      (1)H, and (7)Li NMR spectra and other means, and these data are compared to
      neutral and anionic benchmark compounds. The compound crystallizes as a dimer
      complexed to four THF molecules. The dimer lacks the bridging B-H bonds seen in
      neutral boranes and is instead held together by ionic Li---HB interactions. A
      preliminary scan of reactions with several iodides shows that the compound
      participates in an ionic reduction (with a primary-alkyl iodide), an
      organometallic reduction (Pd-catalyzed with an aryl iodide), and a radical
      reduction (AIBN-initiated with a sugar-derived iodide). Accordingly the new
      borylborohydride class may share properties of both traditional borohydrides and
      isoelectronic N-heterocyclic carbene boranes.

PMID- 20677752
TI  - Enantioselective construction of spiroindolenines by Ir-catalyzed allylic
      alkylation reactions.
AB  - With 2-methyl-1,2,3,4-tetrahydroquinoline-derived phosphoramidite ligand (R,R(a))
      L(6), Ir-catalyzed intramolecular C-3 allylic alkylation of indoles has been
      realized to afford highly enantioenriched spiroindolenine derivatives in 92-98%
      yields with up to >99/1 dr and 97% ee.

PMID- 20677753
TI  - Evidence of adaptability in metal coordination geometry and active-site loop
      conformation among B1 metallo-beta-lactamases .
AB  - Subclass B1 beta-lactamases are Zn(II)-dependent hydrolases that confer bacterial
      resistance to most clinically useful beta-lactam antibiotics. The enzyme BcII
      from Bacillus cereus is a prototypical enzyme that belongs to this group, the
      first Zn(II)-dependent beta-lactamase to be discovered. Crucial aspects of the
      BcII catalytic mechanism and metal binding mode have been assessed mostly on the
      Co(II)-substituted surrogate. Here we report a high-resolution structure of
      Co(II)-BcII, revealing a metal coordination geometry identical to that of the
      native zinc enzyme. In addition, a high-resolution structure of the apoenzyme,
      together with structures with different degrees of metal occupancy and oxidation
      levels of a conserved Cys ligand, discloses a considerable mobility of two loops
      containing four metal ligands (namely, regions His116-Arg121 and Gly219-Cys221).
      This flexibility is expected to assist in the structural rearrangement of the
      metal sites during catalytic turnover, which, along with the coordination
      geometry adaptability of Zn(II) ions, grants the interaction with a variety of
      substrates, a characteristic feature of B1 metallo-beta-lactamases.

PMID- 20677754
TI  - Comment on gas/particle partitioning of two acid-base active compounds in
      mainstream tobacco smoke: nicotine and ammonia.

PMID- 20677756
TI  - Reagent for the detection of protein thiocarboxylates in the bacterial proteome:
      lissamine rhodamine B sulfonyl azide.
AB  - Protein thiocarboxylates are involved in the biosynthesis of thiamin,
      molybdopterin, thioquinolobactin, and cysteine. Sequence analysis suggests that
      this post-translational modification is widely distributed in bacteria. Here we
      describe the development of lissamine rhodamine B sulfonyl azide as a sensitive
      click reagent for the detection of protein thiocarboxylates and describe the use
      of this reagent to detect PdtH, a putative protein thiocarboxylate involved in
      the biosynthesis of the pyridine dithiocarboxylic acid siderophore, in the
      Pseudomonas stutzeri proteome.

PMID- 20677757
TI  - Quantum chemical modeling of benzene ethylation over H-ZSM-5 approaching chemical
      accuracy: a hybrid MP2:DFT study.
AB  - The alkylation of benzene by ethene over H-ZSM-5 is analyzed by means of a hybrid
      MP2:DFT scheme. Density functional calculations applying periodic boundary
      conditions (PBE functional) are combined with MP2 energy calculations on a series
      of cluster models of increasing size which allows extrapolation to the periodic
      MP2 limit. Basis set truncation errors are estimated by extrapolation of the MP2
      energy to the complete basis set limit. Contributions from higher-order
      correlation effects are accounted for by CCSD(T) coupled cluster calculations.
      The sum of all contributions provides the "final estimates" for adsorption
      energies and energy barriers. Dispersion contributes significantly to the
      potential energy surface. As a result, the MP2:DFT potential energy profile is
      shifted downward compared to the PBE profile. More importantly, this shift is not
      the same for reactants and transition structures due to different self
      interaction correction errors. The final enthalpies for ethene, benzene, and
      ethylbenzene adsorption on the Bronsted acid site at 298 K are -46, -78, and -110
      kJ/mol, respectively. The intrinsic enthalpy barriers at 653 K are 117 and 119/94
      kJ/mol for the one- and two-step alkylation, respectively. Intrinsic rate
      coefficients calculated by means of transition state theory are converted to
      apparent Arrhenius parameters by means of the multicomponent adsorption
      equilibrium. The simulated apparent activation energy (66 kJ/mol) agrees with
      experimental data (58-76 kJ/mol) within the uncertainty limit of the
      calculations. Adsorption energies obtained by adding a damped dispersion term to
      the PBE energies (PBE+D), agree within +/-7 kJ/mol, with the "final estimates",
      except for physisorption (pi-complex formation) and chemisorption of ethene
      (ethoxide formation) for which the PBE+D energies are 12.4 and 26.0 kJ/mol,
      respectively larger than the "final estimates". For intrinsic energy barriers,
      the PBE+D approach does not improve pure PBE results.

PMID- 20677758
TI  - Cyanation of arenes via iridium-catalyzed borylation.
AB  - We report a method to conduct one-pot meta cyanation of arenes by iridium
      catalyzed C-H borylation and copper-mediated cyanation of the resulting
      arylboronate esters. This process relies on a method to conduct the cyanation of
      arylboronic esters, and conditions for this new transformation are reported.
      Conditions for the copper-mediated cyanation of arylboronic acids are also
      reported. By the resulting sequence of borylation and cyanation, 1,3
      disubstituted and 1,2,3-trisubstituted arenes and heteroarenes containing halide,
      ketone, ester, amide, and protected alcohol functionalities are converted to the
      corresponding meta-substituted aryl nitriles. The utility of this methodology is
      demonstrated through the conversion of a protected 2,6-disubstituted phenol to 4
      cyano-2,6-dimethylphenol, which is an intermediate in the synthesis of the
      pharmaceutical etravirine. The utility of the method is further demonstrated by
      the conversion of 3-chloro-5-methylbenzonitrile, produced through the one-pot C-H
      borylation and cyanation sequence, to the corresponding 3,5-disubstituted
      aldehydes, ketones, amides, carboxylic acids, tetrazoles, and benzylamines.

PMID- 20677759
TI  - Reversal of Hofmeister ordering for pairing of NH4(+) vs alkylated ammonium
      cations with halide anions in water.
AB  - Pairing of halide anions with ammonium, as well as with trialkylated and
      tetraalkylated ammonium cations in water, is investigated by molecular dynamics
      simulations, which are verified by ab initio calculations and experimental excess
      chemical potentials. We find that ammonium prefers to pair with smaller halides
      over the larger ones, while the order is reversed for tetraalkylated ammonium
      cations. Trialkylated ammonium cations exhibit an intermediate behavior, with the
      acidic hydrogen preferring smaller anions and alkyl chains interacting
      attractively with larger halides. This Hofmeister reversal of anionic ordering
      upon tetraalkylation of the ammonium cation is robustly predicted by both
      nonpolarizable and polarizable force fields and supported by experimental
      evidence.

PMID- 20677760
TI  - A biomimetic asymmetric responsive single nanochannel.
AB  - Artificial single nanochannels have emerged as possible candidates for mimicking
      the process of ionic transport in ion channels and boosting the development of
      bioinspired intelligent nanomachines for real-world applications, such as
      biosensors, molecular filtration, and nanofluidic devices. One challenge that
      remains is to make the artificial nanochannel "smart", with various functions
      like an organism in Nature. The components of ion channels are asymmetrically
      distributed between membrane surfaces, which are significant for the
      implementation of the complex biological function. Inspired by this natural
      asymmetrical design, here we develop a biomimetic asymmetric responsive single
      nanochannel system that displays the advanced feature of providing control over
      pH- and temperature-tunable asymmetric ionic transport properties through
      asymmetric modifications inside the single nanochannels, which could be
      considered as a primal platform for the simulation of different ionic transport
      processes as well as the enhancement of the functionality of ion channels.

PMID- 20677761
TI  - Leucine-rich pentatricopeptide-repeat containing protein regulates mitochondrial
      transcription.
AB  - Mitochondrial function depends upon the coordinated expression of the
      mitochondrial and nuclear genomes. Although the basal factors that carry out the
      process of mitochondrial transcription are known, the regulation of this process
      is incompletely understood. To further our understanding of mitochondrial gene
      regulation, we identified proteins that bound to the previously described point
      of termination for the major mRNA-coding transcript H2. One was the leucine-rich
      pentatricopeptide-repeat containing protein (LRPPRC), which has been linked to
      the French-Canadian variant of Leigh syndrome. Cells with reduced expression of
      LRPPRC had a reduction in oxygen consumption. The expression of mitochondrial
      mRNA and tRNA was dependent upon LRPPRC levels, but reductions in LRPPRC did not
      affect the expression of mitochondrial rRNA. Reduction of LRPPRC levels
      interfered with mitochondrial transcription in vitro but did not affect the
      stability of mitochondrial mRNAs or alter the expression of nuclear genes
      responsible for mitochondrial transcription in vivo. These findings demonstrate
      the control of mitochondrial mRNA synthesis by a protein that has an established
      role in regulating nuclear transcription and a link to mitochondrial disease.

PMID- 20677762
TI  - [Mn(III)4Ln(III)4] calix[4]arene clusters as enhanced magnetic coolers and
      molecular magnets.
AB  - The use of methylene-bridged calix[4]arenes in 3d/4f chemistry produces a family
      of clusters of general formula
      [Mn(III)(4)Ln(III)(4)(OH)(4)(C4)(4)(NO(3))(2)(DMF)(6)(H(2)O)(6)](OH)(2) (where C4
      = calix[4]arene; Ln = Gd (1), Tb (2), Dy (3)). The molecular structure describes
      a square of Ln(III) ions housed within a square of Mn(III) ions. Magnetic studies
      reveal that 1 has a large number of molecular spin states that are populated even
      at the lowest investigated temperatures, while the ferromagnetic limit S = 22 is
      being approached only at the highest applied fields. This, combined with the high
      magnetic isotropy, makes the complex an excellent magnetic refrigerant for low
      temperature applications. Replacement of the isotropic Gd(III) ions with the
      anisotropic Tb(III) and Dy(III) ions "switches" the magnetic properties of the
      cluster so that 2 and 3 behave as low-temperature molecular magnets, displaying
      slow relaxation of the magnetization.

PMID- 20677763
TI  - Electron transport properties of atomic carbon nanowires between graphene
      electrodes.
AB  - Long, stable, and free-standing linear atomic carbon wires (carbon chains) have
      been carved out from graphene recently [Meyer et al. Nature (London) 2008, 454,
      319; Jin et al. Phys. Rev. Lett. 2009, 102, 205501]. They can be considered as
      extremely narrow graphene nanoribbons or extremely thin carbon nanotubes. It
      might even be possible to make use of high-strength and identical (without
      chirality) carbon wires as a transport channel or on-chip interconnects for field
      effect transistors. Here we investigate electron transport properties of linear
      atomic carbon wire-graphene junctions by combining nonequilibrium Green's
      function with density functional theory. For short wires, linear ballistic
      transport is observed in wires consisting of odd numbers of carbon atoms but not
      in those consisting of even numbers of carbon atoms. For wires longer than 2.1 nm
      as fabricated above, however, the ballistic conductance of carbon wire-graphene
      junctions is independent of the structural distortion, structural imperfections,
      and hydrogen impurity adsorbed on the linear carbon wires, except for oxygen
      impurity adsorption under a low bias. As such, the epoxy groups might be the
      origin of experimentally observed low conductance in the carbon chain. Moreover,
      double-atomic carbon chains exhibit a negative differential resistance effect.

PMID- 20677764
TI  - Mimicking the rice leaf--from ordered binary structures to anisotropic
      wettability.
AB  - In this paper, we report a method to fabricate a series of surfaces with large
      area ordered binary arrays by controllable dewetting. The binary structure arrays
      consist of an ordered-stripe array and droplet-row array. In order to expand the
      system, polystyrene (PS) and poly(methyl methacrylate) (PMMA) are introduced in
      this experiment for investigation in detail. Through adjustment of the polymer
      solution concentration and the modified underlying pattern on substrate, the
      surface topographies can be controlled simply. Accordingly, three types of
      topographies with ordered binary arrays have been obtained by thermal annealing.
      These unique surfaces mimic the natural rice leaf structurally, which also
      displays anisotropic wettability for water droplet as natural surfaces. This
      method points out a new way for the manufacture of functional surfaces.

PMID- 20677765
TI  - Quantitative characterization of polymer-polymer, protein-protein, and polymer
      protein interaction via tracer sedimentation equilibrium.
AB  - Quantitative analysis of the composition dependence of the concentration gradient
      of each species of macromolecule within a solution mixture at sedimentation
      equilibrium permits the quantitative characterization of self- and
      heterointeractions between sedimenting solutes. Sedimentation equilibrium
      experiments were conducted on solutions containing a trace concentration of FITC
      labeled BSA in varying concentrations of Ficoll 70 and on solutions containing a
      trace concentration of FITC-labeled Ficoll 70 in varying concentrations of BSA.
      The equilibrium gradient of each solute component in each mixture was measured
      independently. Analysis of the resulting gradients resulted in evaluation of the
      dependence of the activity coefficient of Ficoll upon the concentrations of
      Ficoll and BSA at concentrations of up to 100 g/L and the dependence of the
      activity coefficient of BSA upon the concentrations of Ficoll and BSA at
      concentrations of up to 100 g/L. The activity coefficients of both species
      increase significantly with increasing Ficoll and BSA concentration and do not
      vary with temperature, to within the precision of measurement, over the
      temperature range of 5-37 degrees C, indicating that the dominant interaction
      between Ficoll molecules and between BSA and Ficoll molecules is repulsive and
      probably due to steric volume exclusion. The measured dependences may be
      accounted for quantitatively by a simple model in which BSA and Ficoll 70 are
      represented by equivalent rigid particles.

PMID- 20677766
TI  - Role of orbital degeneracy in the single molecule magnet behavior of a
      mononuclear high-spin Fe(II) complex.
AB  - To explain the single-molecule magnet behavior of the mononuclear complex
      [(tpaMes)Fe](-) we have developed a model that takes into account the trigonal
      ligand field splitting of the atomic (5)D term of the Fe(II) ion, and the spin
      orbital splitting and mixing of the ligand field terms. The ground ligand field
      term is shown to be the orbital doublet (5)E possessing an unquenched orbital
      angular momentum. We demonstrate that the splitting of this term cannot be
      described by the conventional zero-field splitting Hamiltonian proving thus the
      irrelevance of the spin-Hamiltonian formalism in the present case. The first
      order orbital angular momentum is shown to lead to the strong magnetic anisotropy
      with the trigonal axis being the easy axis of the magnetization.

PMID- 20677767
TI  - Surface effects in water-soluble shell-core hybrid gold nanoparticles in
      oligonucleotide single strand recognition for sequence-specific bioactivation.
AB  - Highly monodisperse water-soluble shell-core hybrid gold nanoparticles were
      prepared by in situ reduction of gold salts in the presence of a bifunctional
      thiol, tiopronin. The resulting particles exhibited diameters of 20-60 nm, as
      characterized by scanning electron microscopy. The tiopronin coating was uniform,
      exposing a carboxylated monolayer surface that was further modified by coupling
      with an amino-maleimide linker. The polar heteroorganic shell rendered these
      materials water-soluble and, as a result, amenable to conditions for coupling
      with molecules of biological importance, for example, thiolated oligonucleotides.
      When brought into contact with a homogeneously dispersed oligonucleotide chain,
      the functionalized shell-core particle binds with a complementary oligonucleotide
      chain with high specificity. Binding could be qualitatively recognized by easily
      observed fluorescence differences. The largest particles (ca. 60 nm diameter)
      were unstable in buffered water, and further condensation ultimately led to
      aggregation and precipitation. In contrast, particles with diameters of 20-30 nm
      were stable in buffered water and were easily further functionalized with matched
      oligonucleotide double strands. This work thus constitutes a new route for the
      preparation of stable modified gold nanoparticles that can be easily further
      modified to deliver a metal core particle in aqueous media, as required for
      recognition, and manipulation, of specific biological sequences. Surface
      properties are key variables for these applications.

PMID- 20677768
TI  - Interactions between polymers and lipid monolayers at the air/water interface:
      surface behavior of poly(methyl methacrylate)-cholesterol mixed films.
AB  - The behavior of mixed monolayers of cholesterol and poly(methyl methacrylate)
      (PMMA) with molecular weights of M(w) = 120,000 g/mol and M(w) = 15,000 g/mol was
      investigated at the air/water interface using Langmuir and Brewster angle
      microscopy techniques. From the data of surface pressure (pi)-area (A) isotherms,
      compressional modulus-surface pressure (C(s)(-1)-pi) curves, and film thickness,
      complemented with Brewster angle microscopy images, the interaction between the
      components was analyzed. Regardless of the surface pressure (pi = 10, 20, or 30
      mN/m) at which the mean molecular/monomer areas (Am) were calculated, the Am-mole
      fraction plots (corresponding to X(PMMA) = 0.1, 0.3, 0.5, 0.7, and 0.9) show that
      all the experimental points obtained are placed on the theoretical straight line
      calculated according to the additivity rule. This fact, together with the
      existence of two collapses in the mixed monolayers and with the fact that the
      surface pressure of the liquid-expanded LE-L'E phase transition of PMMA does not
      change with the monolayer composition, demonstrates the immiscibility of the film
      components at the interface. The application of the Crisp phase rule to the phase
      diagram of PMMA-cholesterol mixed monolayers helps to explain the existence of a
      biphasic system, regardless of their composition and surface pressure. Besides,
      Brewster angle microscopy (BAM) images showed the existence of heterogeneous
      cholesterol domains with high reflectivity immersed in a homogeneous polymer
      separate phase with low reflectivity.

PMID- 20677769
TI  - Imaging the carrier photogeneration in nanoscale phase segregated organic
      heterojunctions by Kelvin probe force microscopy.
AB  - In this work, we spatially resolve by Kelvin probe force microscopy (KPFM) under
      ultrahigh vacuum (UHV) the surface photovoltage in high-efficiency nanoscale
      phase segregated photovoltaic blends of poly(3-hexylthiophene) and [6,6]-phenyl
      C61 butyric acid methyl ester. The spatial resolution achieved represents a 10
      fold improvement over previous KPFM reports on organic solar cells. By combining
      the damping contrast to the topographic data in noncontact atomic force
      microscopy under UHV, surface morphologies of the interpenetrated networks are
      clearly revealed. We show how the lateral resolution in KPFM can be significantly
      enhanced by optimizing the damping signal, allowing a direct visualization of the
      carrier generation at the donor-acceptor interfaces and their transport through
      the percolation pathways in the nanometer range. Henceforth, high-resolution KPFM
      has the potential to become a routine characterization tool for organic and
      hybrid photovoltaics.

PMID- 20677770
TI  - Superior reinforcement in melt-spun polyethylene/multiwalled carbon nanotube
      fiber through formation of a shish-kebab structure.
AB  - The formation of a shish kebab (SK) structure, where carbon nanotubes (CNTs)
      serve as shish and polymer lamellae serve as kebab, is particularly interesting
      and provides a novel way to enhance the polymer-CNT interface. A fine SK
      structure is achieved through melt spinning. High density polyethylene and
      pristine CNTs were first compounded in an extruder. The compound was then spun
      into fibers with different draw ratios with the aid of a capillary rheometer. The
      crystalline structure and mechanical behavior were characterized by scanning
      electron microscopy, differential scanning calorimetry, two-dimensional wide
      angle X-ray scattering, polarized Raman spectroscopy, and tensile testing. An
      increase in tensile strength as high as 3 times has been achieved in the fiber.
      The formation of SKs is considered as the main mechanism responsible for the
      enhanced interfacial interaction and excellent tensile property.

PMID- 20677771
TI  - Initial ionization reaction in matrix-assisted laser desorption/ionization.
AB  - The initial ionization reaction in matrix-assisted laser desorption/ionization
      (MALDI) was examined on the basis of the appearance of photoelectrons. The
      threshold laser fluence for the ejection of photoelectrons from 2,5
      dihydroxybenzoic acid (DHB), sinapinic acid (SA), and trihydroxyacetopheone
      (THAP) on stainless steel (SS) substrates was 0.05, 0.41, and 8.39 mJ/cm(2),
      respectively. These values are considerably lower than those for MALDI ions,
      indicating that the electron detachment likely precedes other ionization
      reactions. The SS substrate played an insignificant role in the production of
      photoelectrons because suspended DHB produced a photoelectron signal similar to
      DHB on the SS surface, and decreasing the DHB thickness on the SS reduced the
      photoelectron intensity. For crystalline DHB and SA, the photoelectron intensity
      increased with the laser (337 nm) fluence in a relationship of less than second
      order, suggesting considerable reductions of ionization potentials in comparison
      with free molecules. According to ab initio calculations, the ionization
      potential of DHB clusters reduces as the cluster size increases from monomer to
      octamer. The impact of these abundant electrons on the ion production in MALDI is
      discussed.

PMID- 20677772
TI  - Roles of individual and cooperative motions of molecules in glass-liquid
      transition and crystallization of toluene.
AB  - Deeply supercooled fragile liquid is known to be dynamically heterogeneous, where
      super Arrhenius behavior of shear viscosity and alpha and beta relaxation
      processes have been observed. To clarify origins of these behaviors, we have
      investigated correlations between microscopic molecular diffusion and macroscopic
      hydrodynamics of vapor-deposited toluene films by using time-of-flight secondary
      ion mass spectrometry. The molecules are intermixed gradually at around 70 K on
      the film deposited at 15 K, which is followed by an abrupt film morphology change
      at around the calorimetric glass-transition temperature (T(g)) of 117 K. For the
      film deposited at 100 K, intermixing of the molecules occurs at temperatures over
      100-130 K, but no abrupt increase in diffusivity is recognizable at T(g). This
      result can be explained as dynamical heterogeneity or decoupling between
      translational diffusion and viscosity. The self-diffusion is thought to occur in
      a sub-T(g) region as a precursor state of the glass-liquid transition; that is,
      individual motion in the solid-like state evolves into cooperative motion of
      liquid-like state at T(g). The supercooled liquid nucleates at 147 K, although
      the crystal can grow even at 117 K provided that nuclei preexist. The origins of
      unusual glass transition behaviors of amorphous solid water are also discussed in
      comparison with this standard.

PMID- 20677773
TI  - Fluorescence spectroscopic and time-dependent DFT studies for intramolecular
      excimer formation of Di-9H-fluoren-9-yldimethylsilane: dynamics and energetics
      for conformational change.
AB  - Intramolecular excimer formation of di-9H-fluoren-9-yldimethylsilane in various
      solvents was studied by means of steady-state and time-resolved fluorescence
      spectroscopies. Solvent viscosity effect on the kinetics for the monomer-excimer
      transition was found to be very slight, indicating that the transformation is
      accompanied by a slight conformational change presumably involving a transition
      from a near face-to-face conformer to a true sandwich conformer. The excitation
      energies and the corresponding oscillator strengths were derived with the time
      dependent B3LYP/cc-pVTZ method. The simulated absorption spectrum involving the
      variation of the oscillator strengths in terms of the wavelengths accords with
      the experimental absorption pattern. The TD DFT calculations also reveal that
      excitation energy is significantly decreased with decreasing the interchromophore
      separation and the dihedral angle in a fluorene dimer, as an indication that the
      excimer state emitting the significantly red-shifted fluorescence corresponds to
      a sandwich conformer.

PMID- 20677774
TI  - On-chip Rayleigh imaging and spectroscopy of carbon nanotubes.
AB  - We report a novel on-chip Rayleigh imaging technique using wide-field laser
      illumination to measure optical scattering from individual single-walled carbon
      nanotubes (SWNTs) on a solid substrate with high spatial and spectral resolution.
      This method in conjunction with calibrated AFM measurements accurately measures
      the resonance energies and diameters for a large number of SWNTs in parallel. We
      apply this technique for fast mapping of key SWNT parameters, including the
      electronic-types and chiral indices for individual SWNTs, position and frequency
      of chirality-changing events, and intertube interactions in both bundled and
      distant SWNTs.

PMID- 20677775
TI  - Large signal operation of small band-gap carbon nanotube-based ambipolar
      transistor: a high-performance frequency doubler.
AB  - A small band-gap carbon nanotube (SBG CNT) with a large diameter of 4 nm has been
      used to fabricate ambipolar field-effect transistors (FETs) with ultrahigh
      carrier mobility of more than 18 300 and 8300 cm(2)/V x s for holes and
      electrons, respectively. Using a top-gate device geometry with 12 nm HfO(2) being
      the gate oxide, the SBG CNT-based FET exhibits an almost perfect symmetric
      ambipolar transfer characteristic without any noticeable hysteresis, and a highly
      efficient frequency doubler is constructed based on this near perfect ambipolar
      FET. The SBG CNT-based frequency doubler is shown to be able to operate in a
      large signal mode where the input AC signal, being applied to the top-gate
      electrode, drives the FET operating alternatively in a p- or n-region yielding an
      output signal at the drain electrode with doubled frequency and high conversion
      efficiency. For an input AC signal of 1 kHz, detailed frequency power spectrum
      analysis shows that more than 95% of the output signal is concentrated at the
      doubled frequency at 2 kHz, with a gain of more than 0.15, and this represents
      the highest gain so far achieved in carbon-based devices, including graphene
      based devices.

PMID- 20677776
TI  - Do prokaryotes have more kinetically stable proteins than eukaryotic organisms?
AB  - Upon folding, some proteins become conformationally trapped, presumably to
      protect against aggregation or premature degradation. To probe the occurrence of
      this property, known as kinetic stability, we used a diagonal two-dimensional
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis method to probe
      biologically diverse organisms. The results show that kinetic stability is
      prevalent in prokaryotes, especially thermophiles, but uncommon in eukaryotic
      organisms, thereby suggesting that this property might be crucial for the
      adaptation and survival of less complex prokaryotic organisms.

PMID- 20677777
TI  - Thermal decomposition pathways of hydroxylamine: theoretical investigation on the
      initial steps.
AB  - Hydroxylamine (NH(2)OH) is an unstable compound at room temperature, and it has
      been involved in two tragic industrial incidents. Although experimental studies
      have been carried out to study the thermal stability of hydroxylamine, the
      detailed decomposition mechanism is still in debate. In this work, several
      density functional and ab initio methods were used in conjunction with several
      basis sets to investigate the initial thermal decomposition steps of
      hydroxylamine, including both unimolecular and bimolecular reaction pathways. The
      theoretical investigation shows that simple bond dissociations and unimolecular
      reactions are unlikely to occur. The energetically favorable initial step of
      decomposition pathways was determined as a bimolecular isomerization of
      hydroxylamine into ammonia oxide with an activation barrier of approximately 25
      kcal/mol at the MPW1K level of theory. Because hydroxylamine is available only in
      aqueous solutions, solvent effects on the initial decomposition pathways were
      also studied using water cluster methods and the polarizable continuum model
      (PCM). In water, the activation barrier of the bimolecular isomerization reaction
      decreases to approximately 16 kcal/mol. The results indicate that the bimolecular
      isomerization pathway of hydroxylamine is more favorable in aqueous solutions.
      However, the bimolecular nature of this reaction means that more dilute aqueous
      solution will be more stable.

PMID- 20677778
TI  - Functional role of Thr-312 and Thr-315 in the proton-transfer pathway in ba3
      Cytochrome c oxidase from Thermus thermophilus.
AB  - Cytochrome ba(3) from Thermus thermophilus is a member of the family of B-type
      heme-copper oxidases, which have a low degree of sequence homology to the well
      studied mitochondrial-like A-type enzymes. Recently, it was suggested that the
      ba(3) oxidase has only one pathway for the delivery of protons to the active site
      and that this pathway is spatially analogous to the K-pathway in the A-type
      oxidases [Chang, H.-Y., et al. (2009) Proc. Natl. Acad. Sci. U.S.A. 106, 16169
      16173]. This suggested pathway includes two threonines at positions 312 and 315.
      In this study, we investigated the time-resolved reaction between fully reduced
      cytochrome ba(3) and O(2) in variants where Thr-312 and Thr-315 were modified.
      While in the A-type oxidases this reaction is essentially unchanged in variants
      with the K-pathway modified, in the Thr-312 --> Ser variant in the ba(3) oxidase
      both reactions associated with proton uptake from solution, the P(R) --> F and F 
      -> O transitions, were slowed compared to those of wild-type ba(3). The observed
      time constants were slowed approximately 3-fold (for P(R) --> F, from 60 to
      approximately 170 mus in the wild type) and approximately 30-fold (for F --> O,
      from 1.1 to approximately 40 ms). In the Thr-315 --> Val variant, the F --> O
      transition was approximately 5-fold slower (5 ms) than for the wild-type oxidase,
      whereas the P(R) --> F transition displayed an essentially unchanged time
      constant. However, the uptake of protons from solution was a factor of 2 slower
      and decoupled from the optical P(R) --> F transition. Our results thus show that
      proton uptake is significantly and specifically inhibited in the two variants,
      strongly supporting the suggested involvement of T312 and T315 in the transfer of
      protons to the active site during O(2) reduction in the ba(3) oxidase.

PMID- 20677779
TI  - Product analysis and inhibition studies of a causative Asn to Ser variant of 4
      hydroxyphenylpyruvate dioxygenase suggest a simple route to the treatment of
      Hawkinsinuria.
AB  - Hawkinsinuria is a severe inherited condition that has a significant impact on
      the health of infants. The disease manifests as metabolic acidosis that
      significantly slows the growth rate and induces persistent diarrhea and vomiting.
      Though other causes may exist, an autosomal dominant mutation that alters codon
      241 of the 4-hydroxyphenylpyruvate dioxygenase (HPPD) gene from encoding an
      asparagine to encoding a serine gives rise to the symptoms of the disease. The
      observed pattern of dominance of this mutation belies the paucity of reports of
      this disease in the literature and suggests that it may be rarely diagnosed.
      Diagnosis is based on the presence of 2-amino-3-{[2-(carboxymethyl)-2,5-dihydroxy
      1-cyclohex-3-enyl]sulfanyl}propanoic acid (hawkinsin) in the urine. We have made
      the structurally equivalent mutation in the Streptomyces avermitilis (N245S) and
      rat (N241S) genes and shown that in both cases the N to S variant enzyme forms
      quinolacetic acid in place of the native product 2,5-dihydroxyphenylacetic acid
      (homogentisate). Importantly, the variant enzyme is highly active, establishing
      the basis for dominant pedigree pattern. Quinolacetic acid reacts readily by
      Michael addition with cellular thiols to form a two-electron oxidized form of
      hawkinsin. The N to S variants are also susceptible to inhibition by 2-[2-nitro-4
      (trifluoromethyl)benzoyl]-1,3-cyclohexanedione (NTBC), a known inhibitor of wild
      type HPPD. NTBC has been approved for use in the treatment of type I tyrosinemia
      and as such has an extensive history of use with infants. The N to S variant
      undergoes an apparent three-step binding mechanism with NTBC that forms with rate
      constants similar to those observed for the wild-type enzyme. Moreover, the
      extreme stability of the HPPD.NTBC complex suggests that NTBC would be a potent
      therapeutic for Hawkinisinuria that would alleviate the extreme frailty
      experienced in the early life period.

PMID- 20677780
TI  - A mutate-and-map strategy for inferring base pairs in structured nucleic acids:
      proof of concept on a DNA/RNA helix.
AB  - We propose a rapid chemical strategy for identifying base pairs in structured
      nucleic acid systems. The approach goes beyond traditional chemical mapping
      approaches by monitoring perturbations of each residue's chemical accessibility
      in response to systematic mutagenesis of residues that are distant in sequence
      but nearby in three dimensions. As a proof of concept, we present high-throughput
      dimethyl sulfate accessibility data for a chimeric DNA/RNA system in which every
      possible sequence variation and deletion in a 20 bp region has been synthesized
      and tested. The data demonstrate that 88% of the system's base pairs can be
      robustly inferred, with A/A and T/C DNA/RNA mismatches giving the strongest
      signals. These results point to the feasibility of rapid base pair inference in
      larger and more complex nucleic acid systems with unknown structure.

PMID- 20677781
TI  - Neuroprotective xanthone glycosides from Swertia punicea.
AB  - Two new dimeric xanthone O-glycosides, puniceasides A (1) and B (2), a new
      trimeric O-glycoside, puniceaside C (3), and two new trimeric C-glycosides,
      puniceasides D (4) and E (5), together with 12 known xanthones were isolated from
      the entire plant of Swertia punicea. The structures of 1-5 were determined by
      HRESIMS and NMR spectroscopic methods. Compounds 2, 6, and 7 exhibited potent
      neuroprotective activity against H(2)O(2)-induced PC12 cell damage.

PMID- 20677782
TI  - Xylorumphiins A-D, mexicanolide limonoids from the seed kernels of Xylocarpus
      rumphii.
AB  - Four new mexicanolide limonoids, named xylorumphiins A-D (1-4), were isolated
      from the seed kernels of Xylocarpus rumphii, together with three known limonoids.
      Their structures and configurations were established on the basis of
      spectroscopic data.

PMID- 20677783
TI  - Diffusion-driven crystal structure transformation: synthesis of Heusler alloy
      Fe3Si nanowires.
AB  - We report fabrication of Heusler alloy Fe(3)Si nanowires by a diffusion-driven
      crystal structure transformation method from paramagnetic FeSi nanowires.
      Magnetic measurements of the Fe(3)Si nanowire ensemble show high-temperature
      ferromagnetic properties with T(c) >> 370 K. This methodology is also
      successfully applied to Co(2)Si nanowires in order to obtain metal-rich nanowires
      (Co) as another evidence of the structural transformation process. Our newly
      developed nanowire crystal transformation method would be valuable as a general
      method to fabricate metal-rich silicide nanowires that are otherwise difficult to
      synthesize.

PMID- 20677784
TI  - Phenolic acids and flavonoids in nonfermented and fermented red sorghum (Sorghum
      bicolor (L.) Moench).
AB  - This study aimed to identify phenolic acids and flavonoids in the red sorghum
      variety PAN 3860 and to determine changes in their concentrations during
      fermentation with lactobacilli. Sorghum sourdoughs fermented with two binary
      strain combinations, Lactobacillus plantarum and Lactobacillus casei or
      Lactobacillus fermentum and Lactobacillus reuteri , were compared to chemically
      acidified controls. Four glycerol esters were tentatively identified,
      caffeoylglycerol, dicaffeoylglycerol, coumaroyl-caffeoylglycerol, and coumaroyl
      feruloylglycerol, that have previously not been detected in sorghum. Chemical
      acidification resulted in hydrolysis of phenolic acid esters and flavonoid
      glucosides. During lactic fermentation, phenolic acids, phenolic acid esters, and
      flavonoid glucosides were metabolized. Analysis of ferulic acid, caffeic acid,
      and naringenin-glucoside contents in single-strain cultures of lactobacilli
      demonstrated that glucosidase, phenolic acid reductase, and phenolic acid
      decarboxylase activities contributed to polyphenol metabolism. This study
      demonstrates that microbial fermentation of sorghum affects the content of
      polyphenols and can influence the nutritional value and antimicrobial activity of
      sorghum.

PMID- 20677785
TI  - In vivo imaging and toxicity assessments of fluorescent nanodiamonds in
      Caenorhabditis elegans.
AB  - Nanoscale carbon materials hold great promise for biotechnological and biomedical
      applications. Fluorescent nanodiamond (FND) is a recent new addition to members
      of the nanocarbon family. Here, we report long-term in vivo imaging of FNDs in
      Caenorhabditis elegans (C. elegans) and explore the nano-biointeractions between
      this novel nanomaterial and the model organism. FNDs are introduced into wild
      type C. elegans by either feeding them with colloidal FND solution or
      microinjecting FND suspension into the gonads of the worms. On feeding, bare FNDs
      stay in the intestinal lumen, while FNDs conjugated with biomolecules (such as
      dextran and bovine serum albumin) are absorbed into the intestinal cells. On
      microinjection, FNDs are dispersed in the gonad and delivered to the embryos and
      eventually into the hatched larvae in the next generation. The toxicity
      assessments, performed by employing longevity and reproductive potential as
      physiological indicators and measuring stress responses with use of reporter
      genes, show that FNDs are stable and nontoxic and do not cause any detectable
      stress to the worms. The high brightness, excellent photostability, and nontoxic
      nature of the nanomaterial have enabled continuous imaging of the whole digestive
      system and tracking of the cellular and developmental processes of the living
      organism for several days.

PMID- 20677788
TI  - The interaction of Li+ with single-layer and few-layer graphene.
AB  - The interaction of Li(+) with single and few layer graphene is reported. In situ
      Raman spectra were collected during the electrochemical lithiation of the single-
      and few-layer graphene. While the interaction of lithium with few layer graphene
      seems to resemble that of graphite, single layer graphene behaves very
      differently. The amount of lithium absorbed on single layer graphene seems to be
      greatly reduced due to repulsion forces between Li(+) at both sides of the
      graphene layer.

PMID- 20677789
TI  - Demonstration of thermal plasma gasification/vitrification for municipal solid
      waste treatment.
AB  - Thermal plasma treatment has been regarded as a viable alternative for the
      treatment of highly toxic wastes, such as incinerator residues, radioactive
      wastes, and medical wastes. Therefore, a gasification/vitrification unit for the
      direct treatment of municipal solid waste (MSW), with a capacity of 10 tons/day,
      was developed using an integrated furnace equipped with two nontransferred
      thermal plasma torches. The overall process, as well as the analysis of
      byproducts and energy balance, has been presented in this paper to assess the
      performance of this technology. It was successfully demonstrated that the thermal
      plasma process converted MSW into innocuous slag, with much lower levels of
      environmental air pollutant emissions and the syngas having a utility value as
      energy sources (287 Nm3/MSW-ton for H2 and 395 Nm3/MSW-ton for CO), using 1.14
      MWh/MSW-ton of electricity (thermal plasma torch (0.817 MWh/MSW-ton)+utilities
      (0.322 MWh/MSW-ton)) and 7.37 Nm3/MSW-ton of liquefied petroleum gas.

PMID- 20677790
TI  - Syntheses of selenolato-bridged dinuclear hydridoplatinum complexes [Pt2H2(mu
      Se(t)Bu)2(PPh3)2] and [Pt2H(Se(t)Bu)(mu-Se(t)Bu)2(PPh3)2]: unusual thermal
      reaction of hydrido(1,1-dimethylethaneselenolato) platinum complex cis
      [PtH(Se(t)Bu)(PPh3)2].
AB  - Novel selenolato-bridged dinuclear hydridoplatinum complexes, cis-[Pt(2)H(2)(mu
      Se(t)Bu)(2)(PPh(3))(2)] (2) and cis-[Pt(2)H(Se(t)Bu)(mu-Se(t)Bu)(2)(PPh(3))(2)]
      (3) were synthesized in 30% and 57% yields, respectively, by the thermolysis of
      hydrido(1,1-dimethylethaneselenolato) Pt(II) complex cis
      [PtH(Se(t)Bu)(PPh(3))(2)] (1) in toluene at 80 degrees C for 3 h. The structures
      of dinuclear complexes 2 and 3 were fully characterized on the basis of their NMR
      and IR spectroscopic data and X-ray crystallography. The two distorted square
      planar Pt atoms in 2 and 3 are held together by two bridged selenolato ligands,
      (t)Bu groups of which adopt a trans configuration with respect to the four
      membered Pt(2)Se(2) ring. Each central Pt(2)Se(2) ring in 2 and 3 has a hinged
      arrangement due to the steric repulsion among the two PPh(3) ligands and the
      (t)Bu group lying between them.

PMID- 20677791
TI  - His-oriented peptide hydrolysis promoted by cis-[Pt(en)(H2O)2]2+: a new specific
      peptide cleavage site.
AB  - The new specific hydrolysis of histidine-containing peptides promoted by cis
      [Pt(en)(H(2)O)(2)](2+) was investigated by electrospray ionization mass
      spectrometry (ESI-MS) and nuclear magnetic resonance spectrometry (NMR). MS
      determination demonstrated that cis-[Pt(en)(H(2)O)(2)](2+) anchors to AcGHG with
      the stoichiometry of either 1:1 or 2:1 (Pt/peptide), but only with 1:1
      stoichoimetry to AcGHL. Cis-[Pt(en)(H(2)O)(2)](2+) is able to promote the
      cleavage of the first downstream peptide bond from histidine at 60 degrees C and
      pH 2.65, and Pt-anchored peptides are the essential intermediates for the
      promoted hydrolysis. Moreover, the larger amount of Pt(II) complex results in
      higher fragmental yield and higher hydrolysis rate. In the presence of 1 equiv of
      Pt(II) complex, (1)H NMR determination confirmed the apparent first-order
      kinetics of the Pt(II)-promoted hydrolysis and the hydrolysis rate for AcGHG and
      AcGHL is 0.20 day(-1) and 0.14 day(-1), respectively. Moreover, Pt(II)
      coordinating to histidine imidazole is the key step to form the Pt(II)-anchored
      peptides. The Pt(II)-activating the first His-downstream carbonyl group via
      synergic coordinating to His imidazole and carbonyl O atom has been proposed for
      the Pt(II)-promoted his-oriented peptide hydrolysis. The lower rate for AcGHL
      should be correlated to the steric hindrance of Leu side chain to the second
      Pt(II) coordinating to tripeptide. In addition, the newly confirmed specific His
      oriented peptide cleavage site implies a new potential strategy for target
      cleavage of peptides or proteins.

PMID- 20677792
TI  - S-adenosyl-L-methionine regulation of the cardiac ryanodine receptor involves
      multiple mechanisms.
AB  - Cardiac contraction is triggered by the release of Ca(2+) via the ryanodine
      receptor (RyR2), a sarcoplasmic reticulum (SR) resident ion channel. RyR2 channel
      activity is modulated through ligand binding and posttranslational regulatory
      mechanisms. S-Adenosyl-l-methionine (SAM), the primary methyl group donor for
      enzyme-mediated methylation of proteins and other biological targets, activates
      RyR2 via an unknown mechanism. Here we show that the SAM-induced increase in
      cardiac SR (CSR) vesicle [(3)H]ryanodine binding is unaffected by
      methyltransferase inhibitors and immunoprecipitation of RyR2 from S-adenosyl-l
      [methyl-(3)H]methionine ([(3)H]SAM) pretreated CSR indicates that RyR2 is not a
      target of SAM-mediated protein methylation. Because SAM contains an adenosine
      moiety and RyR2 is activated by ATP, we investigated whether SAM exerts its
      effects through the adenine nucleotide binding sites on the RyR2 channel. In
      support of this hypothesis, the SAM and ATP concentration dependence of CSR
      vesicle [(3)H]ryanodine binding virtually overlaps. Furthermore, ryanodine
      binding assays show that SAM competes with adenine nucleotide activation of RyR2,
      and the effects of SAM on mean channel open and closed times follow similar
      trends as those observed for ATP. Interestingly, SAM but not ATP activation of
      RyR2 was associated with a marked increase in the percent of channel openings to
      a subconductance level approximately 60% of the maximal single channel
      conductance. This work highlights the complexity underlying SAM regulation of
      RyR2 and suggests ligand binding is among the multiple mechanisms responsible for
      SAM regulation of RyR2.

PMID- 20677793
TI  - Controlling energy gap of bilayer graphene by strain.
AB  - Using the first principles calculations, we show that mechanically tunable
      electronic energy gap is realizable in bilayer graphene if different homogeneous
      strains are applied to the two layers. It is shown that the size of the energy
      gap can be simply controlled by adjusting the strength and direction of these
      strains. We also show that the effect originates from the occurrence of strain
      induced pseudoscalar potentials in graphene. When homogeneous strains with
      different strengths are applied to each layer of bilayer graphene, transverse
      electric fields across the two layers can be generated without any external
      electronic sources, thereby opening an energy gap. The results demonstrate a
      simple mechanical method of realizing pseudoelectromagnetism in graphene and
      suggest a maneuverable approach to fabrication of electromechanical devices based
      on bilayer graphene.

PMID- 20677795
TI  - Synthesis of diamond nanowires using atmospheric-pressure chemical vapor
      deposition.
AB  - We report diamond nanowires grown in an atmospheric pressure chemical vapor
      deposition process. These diamond nanowires are straight, thin and long, and
      uniform in diameter (60-90 nm) over tens of micrometers. Spectroscopic analysis,
      electron diffraction, and transmission electron microscopy provided confirmation
      that these nanowires are diamond with high crystallinity and high structural
      uniformity. They further revealed that these diamond nanowires are encased within
      multiwalled carbon nanotubes.

PMID- 20677794
TI  - Turn-on luminescent probe for cysteine/homocysteine based on a ruthenium(II)
      complex.
AB  - A unique ruthenium(II) complex, tris(4-methyl-2,2'-bipyridyl-4'
      carboxaldehyde)Ru(II) hexafluorophosphate [Ru(CHO-bpy)(3)](PF(6))(2), has been
      designed and synthesized as a highly sensitive and selective luminescence probe
      for the recognition and detection of cysteine (Cys) and homocysteine (Hcy). The
      almost non-luminescent probe can rapidly react with Cys and Hcy to yield the
      corresponding thiazolidine and thiazinane derivatives, accompanied by the
      remarkable luminescence enhancement and a large blue-shift of the maximum
      emission wavelength from 720 to 635 nm. The dose-dependent luminescence
      enhancement of the probe shows a good linearity in the Cys/Hcy concentration
      range of 15 to 180 microM with the detection limits of 1.41 microM and 1.19
      microM for Cys and Hcy, respectively. Furthermore, the luminescence response of
      the probe is highly specific to Cys/Hcy only even in the presence of various
      amino acids, protein, and DNA. The results of this work not only demonstrate the
      efficacy and advantages of the Ru(II) complex-based luminescence probe for the
      sensitive and selective detection of Cys/Hcy but also provide a useful strategy
      for the rational design of Ru(II) complex-based luminescence probes for various
      biological molecules.

PMID- 20677796
TI  - The bis metallacyclic anion [U(N{SiMe3}2)(CH2SiMe2N{SiMe3})2]-.
AB  - A series of bis metallacyclic compounds
      [M(THF)(x)UN*(CH(2)SiMe(2)N{SiMe(3)})(2)](n) [M = Na (2), Li (3), or K (4), N* =
      N(SiMe(3))(2)] were isolated from reactions of UCl(4) or [UN*(3)Cl] with MN* or
      by treatment of [UN*(2)(CH(2)SiMe(2)N{SiMe(3)})] (1) or [UN*(3)] with MN*, MH, or
      LiCH(2)SiMe(3) in tetrahydrofuran (THF). Crystals of 2a x 1/6n-pentane (x = 0),
      2b (x = 1), 2c (x = 2), and 4b (x = 1) were obtained by crystallization of 2 and
      4 from pentane, and [Na(18-crown-6)(THF)][UN*(CH(2)SiMe(2)N{SiMe(3)})(2)] (2d)
      and [Na(15-crown-5)][UN*(CH(2)SiMe(2)N{SiMe(3)})(2)] (2e) were formed upon
      addition of the crown ether. The crystal structures of 2a-2e and 4b exhibit the
      same [UN*(CH(2)SiMe(2)N{SiMe(3)})(2)] units which are linked to Na or K atoms via
      methylene or methyl groups, giving either tight cation-anion pairs (2d and 2e) or
      one-dimensional (1D) or two-dimensional (2D) polymeric compounds with Na or K
      atoms in bridging position between methylene groups of adjacent units. Reaction
      of 2 with CO gave the double insertion derivative
      [Na(2)(THF)U(2)N*(2)(OC{=CH(2)}SiMe(2)N{SiMe(3)})(4)] (5b) and [Na(15-crown
      5)UN*(OC{=CH(2)}SiMe(2)N{SiMe(3)})(2)] (5c) in the presence of the crown ether.
      Thermal decomposition of 5b gave [Na(2)(THF)U(OC{=CH(2)}SiMe(2)N{SiMe(3)})(3)](2)
      (6), the product of CO insertion into the putative tris metallacycle
      [Na(2)(THF)(x)U(CH(2)SiMe(2)N{SiMe(3)})(3)]. The crystal structures of 5b, 5c,
      and 6 show the interaction of the Na atoms with the exocyclic C=CH(2) bonds.
      Diffusion of CO(2) into a THF solution of 2 led to the formation of
      [Na(THF)(x)UN*(OC{O}CH(2)SiMe(2)N{SiMe(3)})(2)] (7) which crystallized from
      pyridine/pentane to give [Na(THF)(2)(py)(2)UN*(OC{O}CH(2)SiMe(2)N{SiMe(3)})(2)] x
      0.5 py (8 x 0.5 py), the first crystallographically characterized complex
      resulting from CO(2) insertion into a M(CH(2)SiMe(2)N{SiMe(3)}) metallacycle.
      Compound 2 reacted with I(2) to give
      [UN*(CH(2)SiMe(2)N{SiMe(3)})(N{SiMe(3)}SiMe(2)CH(2)I)] (9) which would represent
      a new type of so-called "pendulum" systems resulting from a degenerate sigma bond
      metathesis reaction of U-C and C-I bonds.

PMID- 20677797
TI  - Ab initio study on mixed inorganic/organic ligand sandwich clusters: BzTMC(60),
      TM = Sc-Co.
AB  - We have systematically investigated mixed inorganic/organic ligand sandwich
      clusters comprised of 3d transition metal (TM) atoms with C(60) and benzene (Bz)
      molecules, BzTMC(60), by using all electron density functional theory. We found
      the bonding type between TM and C(60) in the ground state evolves from eta(6) (TM
      = Sc-Cr) to eta(5) (TM = Mn) and then to eta(2) (TM = Fe, Co) with increasing
      number of d electrons of TM. The BzTMC(60) clusters (TM = Sc-Co) are of high
      stability through ionic-covalent interactions. The BzCrC(60) cluster has the
      lowest binding energy due to its largest spin-flip energy and the weakest ionic
      bonding interaction between the CrBz unit and C(60). With the exception of
      BzTiC(60) being triplet, all the BzTMC(60) clusters energetically prefer the
      lowest available spin states, e.g., the ground spin state is either a singlet
      (with an even number of electrons) or a doublet (with an odd number of
      electrons). Moreover, the magnetic properties of BzTMC(60) show clear dependence
      to the bond type between TM and C(60), and the eta(5)-ligand configurations tend
      to be in high spin states.

PMID- 20677798
TI  - Epitaxial graphene on Cu(111).
AB  - The growth of graphene on single crystal Cu(111) has been achieved by thermal
      decomposition of ethylene in an ultrahigh vacuum chamber for the first time. The
      structural and electronic properties of graphene on Cu(111) have been
      investigated by scanning tunneling microscopy and spectroscopy. The nucleation of
      monolayer islands and two predominant domain orientations have been observed,
      which lead to the formation of numerous domain boundaries with increasing
      coverage. These results reveal that reducing the density of domain boundaries is
      one challenge of growing high-quality graphene on copper.

PMID- 20677799
TI  - Role of endosomal escape for disulfide-based drug delivery from colloidal
      mesoporous silica evaluated by live-cell imaging.
AB  - Redox-driven intracellular disulfide-cleavage is a promising strategy to achieve
      stimuli-responsive and controlled drug release. We synthesized colloidal
      mesoporous silica (CMS) nanoparticles with ATTO633-labeled cysteine linked to the
      inner particle core via disulfide-bridges and characterized their cysteine
      release behavior after internalization into HuH7 cells by high-resolution
      fluorescence microscopy. Our study revealed that endosomal escape is a bottleneck
      for disulfide-linkage based drug release. Photochemical opening of the endosome
      leads to successful delivery of fluorescently labeled cysteine to the cytosol.

PMID- 20677800
TI  - One-dimensional metal nanowire assembly via block copolymer soft graphoepitaxy.
AB  - We accomplished a facile and scalable route to linearly stacked, one-dimensional
      metal nanowire assembly via soft graphoepitaxy of block copolymers. A one
      dimensional nanoscale lamellar stack could be achieved by controlling the block
      copolymer film thickness self-assembled within the disposable topographic
      confinement and utilized as a template to generate linear metal nanowire
      assembly. The mechanism underlying this interesting morhpology evolution was
      investigated by self-consistent field theory. The optical properties of metal
      nanowire assembly involved with surface plasmon polariton were investigated by
      first principle calculations.

PMID- 20677801
TI  - Commercial peanut (Arachis hypogaea L.) cultivars in the United States:
      phytosterol composition.
AB  - Phytosterols in commercially grown Runner, Virginia, and Spanish peanuts (n =
      221) from 2005 and 2006 were quantified by a combination of acid hydrolysis and
      alkaline saponification steps followed by gas chromatography-flame ionization
      detection and gas chromatography-mass spectrometry analysis of the trimethylsilyl
      derivatives. Delta(5)-Avenasterol, which partially degrades during acid
      hydrolysis, was quantified after alkaline saponification plus direct analysis of
      the steryl glucosides isolated by solid-phase extraction. beta-Sitosterol,
      Delta(5)-avenasterol, campesterol, and stigmasterol were identified in peanut
      lipid extracts as the dominant sterols by retention time mapping and mass spectra
      with recoveries ~99%. Clerosterol, Delta(5,24(25))-stigmastadienol, Delta(7)
      sitosterol + cycloartenol, and one unidentified sterol were also present but at
      low levels. Free and esterified phytosterols accounted for ~80% of the total
      sterols determined; the remainder was attributed to steryl glucosides. The total
      sterol level in Spanish market type peanuts (144.1 +/- 5.3 mg/100 g) was
      significantly greater than both Runners (127.5 +/- 6.3 mg/100 g) and Virginias
      (129.3 +/- 6.9 mg/100 g) (P < 0.05). Tamspan 90 (146.9 mg/100 g) followed by OLIN
      (138.5 mg/100 g) showed the highest total sterol content among the cultivars
      examined. Cultivar effects were strongly significant (P < 0.001) for all
      phytosterols, whereas production year effects were strongly significant (P <
      0.001) for Delta(5)-avenasterol, Delta(5,24(25))-stigmastadienol, and the
      combined quantities of Delta(7)-sitosterol + cycloartenol, which coeluted.
      Cultivar * year interactions were strongly significant (P < 0.001) in all sterols
      except for Delta(7)-sitosterol + cycloartenol (P < 0.01). Total phytosterol
      contents were markedly higher than those reported in the existing literature for
      Runner and Virginia type peanuts, partially attributed to the inclusion of steryl
      glucosides in the analysis.

PMID- 20677803
TI  - Domino approach for the synthesis of pyrrolo[1,2-alpha]pyrazine from vinyl
      azides.
AB  - A domino synthesis of pyrrolo[1,2-alpha]pyrazine from 1H-2-pyrrolecarbaldehyde
      and readily synthesized vinyl azides was developed. This reaction proceeded under
      relatively mild conditions in the presence of base. Additionally, a possible
      mechanism for the entire sequence is proposed.

PMID- 20677804
TI  - Enantioselective modular synthesis of cyclohexenones: total syntheses of (+)
      crypto- and (+)-infectocaryone.
AB  - A modular synthesis of cyclohexenones is described and applied to the first
      enantioselective total syntheses of (+)-crypto- and (+)-infectocaryone. Key steps
      in the synthesis of cyclohexenones are an iridium-catalyzed allylic alkylation,
      nucleophilic allylation, and ring-closing metathesis. On the way to (+)
      cryptocaryone, a catch and release strategy involving an
      iodolactonization/elimination and a regioselective C-acylation were used.

PMID- 20677802
TI  - XIAP gene expression protects beta-cells and human islets from apoptotic cell
      death.
AB  - Islet transplantation has the potential to treat type I diabetes, however, its
      clinical application is limited due to the massive apoptotic cell death and other
      post-transplantation challenges to islet grafts. Therefore, the objective of this
      study was to determine whether ex vivo transduction of rat insulin producing INS
      1E cells and human islets with adenoviral vector encoding human X-linked
      inhibitor of apoptosis (Adv-hXIAP) can protect them from inflammatory cytokines
      and improve their viability and function. There was dose dependent XIAP gene
      expression. XIAP expression led to decrease in the activities of caspase 3/7, 8
      and 9, resulting in reduced apoptotic cell death induced by a cocktail of
      inflammatory cytokines such as IL-1beta, TNFalpha, and IFNgamma. Prolonged
      normoglycemic control could be achieved by transplantation of Adv-XIAP transduced
      human islets under the kidney capsule of streptozotocin induced diabetic NOD-SCID
      mice. Immunohistological staining of the islets bearing kidney sections at day 42
      after transplantation was positive for insulin. Moreover, the protective effect
      of XIAP was reversed by coadministration of XIAP inhibitor embelin. These results
      indicate that ex vivo transduction of islets with Adv-XIAP will decrease cytokine
      induced apoptosis and improve the outcome of islet transplantation.

PMID- 20677805
TI  - Manganese(II)-octacyanometallate(V) bimetallic ferrimagnets with T(c) from 41 to
      53 K obtained in acidic media.
AB  - A series of three-dimensional (3D) octacyanometallate-based bimetallic magnets,
      {[Mn(H(2)O)][Mn(0.75)(HCOO)(0.5)(H(2)O)(0.5)][W(CN)(8)] x H(2)O}(4n) (1),
      {[Mn(2)(HCOO)(HCOOH)][M(CN)(8)] x H(2)O}(n) (M = W (2) and Mo (3)), and
      {[Mn(2)(HCOO)(HCOOH)][W(CN)(8)] x CH(3)OH}(n) (M = W (4) and Mo (5)), were
      synthesized by the reaction of octacyanometallates A(3)[M(CN)(8)] x nH(2)O (A =
      Na, Cs, and (C(4)H(9))(3)NH; M = W and Mo; and n = 2 or 4) with manganese salt
      (Mn(CH(3)COO)(2) x 4 H(2)O, Mn(ClO(4))(2) x 6 H(2)O, and MnCl(2) x 4 H(2)O) in
      aqueous or methanolic solution containing formic acid. All complexes crystallize
      in the tetragonal or orthorhombic system. Complex 1 shows an unexpected 3D
      network structure by connections of manganese ions and octacyanotangstate
      manganese double layers via cyanide bridges, while other complexes have typical
      structure constructions similar to the reported complexes {[MnL](m)[M(CN)(8)]}(n)
      (L = CH(3)COO(-), Cl(-), and H(2)O), which the CN group of [W(V)(CN)(8)]
      coordinates to eight Mn(II) ions forming a -[W(CN)(8)]-Mn(4)-[W(CN)(8)]-Mn(4)-
      columnar chain, and then all chains share Mn(II) ions as the nodes interlocking
      with each other to form the 3D networks. Magnetic studies indicate that the
      cyanide group mediates the antiferromagnetic coupling between octacyanometallates
      and manganese ions in all complexes, and the ferrimagnetic phase transition
      temperatures are 53, 52, 42, 49, and 41 K for 1-5, respectively.

PMID- 20677806
TI  - C-C bond-forming click synthesis of rotaxanes exploiting nitrile N-oxide.
AB  - A click end-capping reaction exploiting nitrile N-oxide to rotaxane was described
      with emphasis of productivity of the protocol via stable C-C bond formation.
      Establishment of a pH-driven molecular shuttling system was also demonstrated by
      practical neutralization of the sec-ammonium group of the rotaxane axle with
      potassium hydroxide.

PMID- 20677808
TI  - Noise characteristics of charge tunneling via localized states in metal--molecule
      -metal junctions.
AB  - We report the noise characteristics of charge transport through an alkyl-based
      metal--molecule--metal junction. Measurements of the 1/f noise, random telegraph
      noise, and shot noise demonstrated the existence of localized traps in the
      molecular junctions. These three noise measurements exhibited results consistent
      with trap-mediated tunneling activated over approximately 0.4 V by trapping and
      detrapping processes via localized states (or defects). The noise
      characterizations will be useful in evaluating the influences of localized states
      on charge transport in molecular or other electronic junctions.

PMID- 20677807
TI  - Top-down mass analysis of protein tyrosine nitration: comparison of electron
      capture dissociation with "slow-heating" tandem mass spectrometry methods.
AB  - Tyrosine nitration in proteins is an important post-translational modification
      (PTM) linked to various pathological conditions. When multiple potential sites of
      nitration exist, tandem mass spectrometry (MS/MS) methods provide unique tools to
      locate the nitro-tyrosine(s) precisely. Electron capture dissociation (ECD) is a
      powerful MS/MS method, different in its mechanisms to the "slow-heating"
      threshold fragmentation methods, such as collision-induced dissociation (CID) and
      infrared multiphoton dissociation (IRMPD). Generally, ECD provides more
      homogeneous cleavage of the protein backbone and preserves labile PTMs. However
      recent studies in our laboratory demonstrated that ECD of doubly charged nitrated
      peptides is inhibited by the large electron affinity of the nitro group, while
      CID efficiency remains unaffected by nitration. Here, we have investigated the
      efficiency of ECD versus CID and IRMPD for top-down MS/MS analysis of multiply
      charged intact nitrated protein ions of myoglobin, lysozyme, and cytochrome c in
      a commercial Fourier transform ion cyclotron resonance (FT-ICR) mass
      spectrometer. CID and IRMPD produced more cleavages in the vicinity of the sites
      of nitration than ECD. However the total number of ECD fragments was greater than
      those from CID or IRMPD, and many ECD fragments contained the site(s) of
      nitration. We conclude that ECD can be used in the top-down analysis of nitrated
      proteins, but precise localization of the sites of nitration may require either
      of the "slow-heating" methods.

PMID- 20677809
TI  - Substituted dineolignans from Magnolia garrettii.
AB  - In the course of a study on lignan profiles of tropical and subtropical members
      of the Magnoliaceae, Magnolia garrettii, an evergreen tree known from northern
      Thailand, Vietnam, and southern Yunnan (China), was investigated. The work
      resulted in the isolation of two dimeric lignans from the dichloromethane extract
      of the leaves of M. garrettii, garrettilignan A (1) and garrettilignan B (2),
      each substituted with two additional p-allylphenolic moieties. Garrettilignans A
      (1) and B (2) represent new skeletal types within the neolignan class.
      Additionally, four known neolignans, magnolol, honokiol, 4'-methylhonokiol, and
      obovatol, were identified.

PMID- 20677810
TI  - Retinoschisin (RS1) interacts with negatively charged lipid bilayers in the
      presence of Ca2+: an atomic force microscopy study.
AB  - Retinoschisin (RS1) is a retina-specific secreted protein encoding a conserved
      discoidin domain sequence. As an adhesion molecule, RS1 preserves the retinal
      cell architecture and promotes visual signal transduction. In young males, loss
      of-function mutations in the X-linked retinoschisis gene (RS1) cause X-linked
      retinoschisis, a form of progressive blindness. Neither the structure of RS1 nor
      the nature of its anchoring and organization on the plasma membranes is fully
      understood. The discoidin C2 domains of coagulation factors V and VIII are known
      to interact with extracellular phosphatidylserine (PS). In this study we have
      used atomic force microscopy (AFM) to study the interactions of murine
      retinoschisin (Rs1) with supported anionic lipid bilayers in the presence of
      Ca(2+). The bilayers consisting of a single lipid, PS, and mixtures of lipids
      with or without PS were used. Consistent with previous X-ray diffraction studies,
      AFM imaging showed two distinct domains in pure PS bilayers when Ca(2+) was
      present. Upon Rs1 adsorption, these PS and PS-containing mixed bilayers underwent
      fast and extensive reorganization. Protein localization was ascertained by
      immunolabeling. AFM imaging showed the Rs1 antibody bound exclusively to the
      calcium-rich ordered phase of the bilayers pointing to the sequestration of Rs1
      within those domains. This was further supported by the increased mechanical
      strength of these domains after Rs1 binding. Besides, changes in bilayer
      thickness suggested that Rs1 was partially embedded into the bilayer. These
      findings support a model whereby the Rs1 protein binds to PS in the retinal cell
      plasma membranes in a calcium-dependent manner.

PMID- 20677812
TI  - MeLi + LiCl in THF: one heterodimer and no tetramers.
AB  - The structure of the aggregates formed when mixing methyllithium and lithium
      chloride in THF has been studied by multinuclear magnetic resonance at 170 K. The
      data suggest that only one new entity is observed, that is the dimer
      [(MeLi)(LiCl)], in equilibrium (K approximately 0.6) with [MeLi](4) and
      [LiCl](2). NMR diffusion measurements lead to the conclusion that this dimer is
      trisolvated in THF at 170 K, a solvation scheme in agreement with DFT
      computations.

PMID- 20677811
TI  - Thermotoga maritima ribonuclease III. Characterization of thermostable
      biochemical behavior and analysis of conserved base pairs that function as
      reactivity epitopes for the Thermotoga 23S rRNA precursor.
AB  - The cleavage of double-stranded (ds) RNA by ribonuclease III is a conserved early
      step in bacterial rRNA maturation. Studies on the mechanism of dsRNA cleavage by
      RNase III have focused mainly on the enzymes from mesophiles such as Escherichia
      coli. In contrast, neither the catalytic properties of extremophile RNases III
      nor the structures and reactivities of their cognate substrates have been
      described. The biochemical behavior of RNase III of the hyperthermophilic
      bacterium Thermotoga maritima was analyzed using purified recombinant enzyme. T.
      maritima (Tm) RNase III catalytic activity exhibits a broad optimal temperature
      range of approximately 40-70 degrees C, with significant activity at 95 degrees
      C. Tm-RNase III cleavage of substrate is optimally supported by Mg(2+) at >or=1
      mM concentrations. Mn(2+), Co(2+), and Ni(2+) also support activity but with
      reduced efficiencies. The enzyme functions optimally at pH 8 and approximately 50
      80 mM salt concentrations. Small RNA hairpins that incorporate the 16S and 23S
      pre-rRNA stem sequences are efficiently cleaved by Tm-RNase III at sites that are
      consistent with production in vivo of the immediate precursors to the mature
      rRNAs. Analysis of pre-23S substrate variants reveals a dependence of reactivity
      on the base-pair (bp) sequence in the proximal box (pb), a site of protein
      contact that functions as a positive recognition determinant for Escherichia coli
      (Ec) RNase III substrates. The dependence of reactivity on the pb sequence is
      similar to that observed with Ec-RNase III substrates. In fact, Tm-RNase III
      cleaves an Ec-RNase III substrate with identical specificity and is inhibited by
      antideterminant bp that also inhibit Ec-RNase III. These results indicate the
      conservation, across a broad phylogenetic distance, of positive and negative
      determinants of reactivity of bacterial RNase III substrates.

PMID- 20677813
TI  - Iron-containing mesoporous aluminosilicate: a highly active and reusable
      heterogeneous catalyst for hydroarylation of styrenes.
AB  - Hydroarylation of various styrene derivatives has been successfully carried out
      in excellent yield using Fe-Al-MCM-41 catalyst. The C-H functionalization using
      solid heterogeneous catalyst provides a straightforward access to a series of
      important 1,1-diarylalkane products. The catalyst can be recovered and reused at
      least three times without any significant loss in its catalytic activity.

PMID- 20677814
TI  - Observation of vibronic emission spectrum of jet-cooled 3,5-difluorobenzyl
      radical.
AB  - We applied the technique of corona-excited supersonic expansion using a pinhole
      type glass nozzle to observe the vibronic emission spectrum of jet-cooled benzyl
      type radicals from the corona discharge of precursor 3,5-difluorotoluene seeded
      in a large amount of inert helium carrier gas. The vibronically well-resolved
      emission spectrum was recorded with a long-path monochromator in the visible
      region. After subtracting the vibronic bands originating from isomeric
      difluorobenzyl radicals from the observed spectrum, we identified for the first
      time the bands belonging to the 3,5-difluorobenzyl radical, from which the
      electronic energy and vibrational mode frequencies of the 3,5-difluorobenzyl
      radical were accurately determined in the ground electronic state by comparison
      with those of the precursor and with those from an ab initio calculation.

PMID- 20677815
TI  - Zero kinetic energy photoelectron spectroscopy of pyrene.
AB  - We report zero kinetic energy photoelectron (ZEKE) spectroscopy of pyrene via
      resonantly enhanced multiphoton ionization. Our analysis centers on the symmetry
      of the first electronically excited state (S(1)), its vibrational modes, and the
      vibration of the ground cationic state (D(0)). From comparisons between the
      observed vibrational frequencies and those from ab initio calculations at the
      configuration interaction singles level using the 6-311G (d,p) basis set, and
      based on other previous experimental and theoretical reports, we confirm the
      (1)B(2u) symmetry for the S(1) state. This assignment represents a reversal in
      the energy order of the two closely spaced electronically excited states from our
      theoretical calculation, and extensive configuration interactions are attributed
      to this result. Among the observed vibrational levels of the S(1) state, three
      are results of vibronic coupling due to the nearby second electronically excited
      state. The ZEKE spectroscopy obtained via the vibronic levels of the S(1) state
      reveals similar modes for the cation as those of the intermediate state. Although
      we believe that the ground ionic state can be considered a single electron
      configuration, the agreement between theoretical and experimental frequencies for
      the cation is limited. This result is somewhat surprising based on our previous
      work on cata-condensed polycyclic aromatic hydrocarbons and small substituted
      aromatic compounds. Although a relatively small molecule, pyrene demonstrates its
      nonrigidity via several out-of-plane bending modes corresponding to corrugation
      of the molecular plane. The adiabatic ionization potential of neutral pyrene is
      determined to be 59 888 +/- 7 cm(-1).

PMID- 20677816
TI  - Trends in aqueous hydration across the 4f period assessed by reliable
      computational methods.
AB  - The geometric and electronic structures, as well as the thermodynamic properties
      of trivalent lanthanide hydrates {Ln(H(2)O)(8,9)(3+) and
      Ln(H(2)O)(8,9)(H(2)O)(12,14)(3+), Ln = La-Lu} have been examined using
      unrestricted density functional theory (UDFT), unrestricted Moller-Plesset
      perturbation theory (UMP2), and multiconfigurational self-consistent field
      methods (MCSCF). While Ln-hydrates with 2-5 unpaired f-electrons have some
      multiconfigurational character, the correlation energy lies within 5-7 kcal/mol
      across the period and for varying coordination numbers. As such DFT yields
      structural parameters and thermodynamic data quite close to experimental values.
      Both UDFT and UMP2 predict free energies of water addition to the
      Ln(H(2)O)(8)(3+) species to become less favorable across the period; however, it
      is a non-linear function of the surface charge density of the ion. UDFT further
      predicts that the symmetry of the metal-water bond lengths is sensitive to the
      specific f-electron configuration, presumably because of repulsive interactions
      between filled f-orbitals and water lone-pairs. Within the
      Ln(H(2)O)(8,9)(H(2)O)(12,14)(3+) clusters, interactions between solvation shells
      overrides this orbital effect, increasing the accuracy of the geometric
      parameters and calculated vibrational frequencies. Calculated atomic charges
      indicate that the water ligands each donate 0.1 to 0.2 electrons to the Ln(III)
      metals, with increasing electron donation across the period. Significant
      polarization and charge transfer between solvation shells is also observed. The
      relationship between empirical effective charges and calculated atomic charges is
      discussed with suggestions for reconciling the trends across the period.

PMID- 20677817
TI  - Novel fibers increase bone calcium content and strength beyond efficiency of
      large intestine fermentation.
AB  - Dietary fibers are thought to benefit bone health through increasing mineral
      absorption and retention following fermentation in the lower gut and
      solubilization of minerals. This study compared eight fibers to cellulose
      following a 12 week intervention for production of short-chain fatty acids
      (SCFA), calcium absorption, mineral retention and bone content, and bone density
      and strength in a weanling rat model. Benefits to bone were poorly to modestly
      related to SCFA production, calcium absorption, or mineral retention, but some
      parameters were better predicted by cecal content weight, suggesting other
      mechanisms may be important. Nevertheless, two resistant starches, a soluble
      fiber dextrin and Polydextrose, increased bone calcium content. Soluble corn
      fiber and soluble fiber dextrin had the greatest benefit to bone properties
      including whole body bone mineral content and density and greater volumetric bone
      mineral density, cortical thickness and area, and peak breaking strength of the
      distal femur.

PMID- 20677818
TI  - Orthogonal actuation of a supramolecular double-porphyrin tweezer.
AB  - A supramolecular three-component double-porphyrin tweezer (PT) is prepared
      quantitatively using heteroleptic complex formation along the HETTAP methodology.
      Insertion of guest molecules, such as DABCO or pyrazine, into the coupled
      porphyrin cavities of PT leads to an actuation of the double-porphyrin tweezer
      function. Evidence from (1)H NMR, VT NMR, and UV-vis titration suggests a rapid
      association/dissociation of the DABCO molecules at the central porphyrin. Upon
      addition of an equimolar mixture of DABCO and pyrazine to PT, a dynamic five
      component self-assembled structure was furnished exclusively. (1)H NMR and
      K(assoc) values validate the greater stability of the heteroloaded PT-(DABCO)(py)
      system in comparison to the two homoloaded systems, PT-(DABCO)(2) and PT-(py)(2).
      The higher stability of PT-(DABCO)(py) seems to be the result of charge transfer
      from DABCO to the vacant pi* orbital of pyrazine across the porphyrin plane.

PMID- 20677821
TI  - Charge separation process in water clusters containing HCl. Molecular dynamics
      study using semiempirical hamiltonians.
AB  - The acid dissociation of HCl in water clusters was studied using the PM3-MAIS
      model in a direct molecular dynamic simulations framework. Several trajectories
      for each cluster size were computed to improve the sampling on the potential
      energy surface and to increase the statistical significance of our study. We have
      analyzed the emergence of well-defined hydration structures around the ions and
      the effect they have on the charge separation process. Surface and bulk solvation
      situations are examined for both ions in terms of the competing circumstances for
      water molecules in the cluster. Our results show that the prevailing situation in
      all these clusters is a water mediated interaction between the ions. This
      situation is related to the significant interplay of several factors such as
      charge transfer occurring between the ions and their first hydration shells. Our
      results show that no significant charge redistribution occurs during the Eigen
      Zundel transformation.

PMID- 20677820
TI  - Identification of a small molecule inhibitor of importin beta mediated nuclear
      import by confocal on-bead screening of tagged one-bead one-compound libraries.
AB  - In eukaryotic cells, proteins and RNAs are transported between the nucleus and
      the cytoplasm by nuclear import and export receptors. Over the past decade, small
      molecules that inhibit the nuclear export receptor CRM1 have been identified,
      most notably leptomycin B. However, up to now no small molecule inhibitors of
      nuclear import have been described. Here we have used our automated confocal
      nanoscanning and bead picking method (CONA) for on-bead screening of a one-bead
      one-compound library to identify the first such import inhibitor, karyostatin 1A.
      Karyostatin 1A binds importin beta with high nanomolar affinity and specifically
      inhibits importin alpha/beta mediated nuclear import at low micromolar
      concentrations in vitro and in living cells, without perturbing transportin
      mediated nuclear import or CRM1 mediated nuclear export. Surface plasmon
      resonance binding experiments suggest that karyostatin 1A acts by disrupting the
      interaction between importin beta and the GTPase Ran. As a selective inhibitor of
      the importin alpha/beta import pathway, karyostatin 1A will provide a valuable
      tool for future studies of nucleocytoplasmic trafficking.

PMID- 20677822
TI  - GSK4112, a small molecule chemical probe for the cell biology of the nuclear heme
      receptor Rev-erbalpha.
AB  - The identification of nonporphyrin ligands for the orphan nuclear receptor Rev
      erbalpha will enable studies of its role as a heme sensor and regulator of
      metabolic and circadian signaling. We describe the development of a biochemical
      assay measuring the interaction between Rev-erbalpha and a peptide from the
      nuclear receptor corepressor-1 (NCoR). The assay was utilized to identify a small
      molecule ligand for Rev-erbalpha, GSK4112 (1), that was competitive with heme. In
      cells, 1 profiled as a Rev-erbalpha agonist in cells to inhibit expression of the
      circadian target gene bmal1. In addition, 1 repressed the expression of
      gluconeogenic genes in liver cells and reduced glucose output in primary
      hepatocytes. Therefore, 1 is useful as a chemical tool to probe the function of
      Rev-erbalpha in transcriptional repression, regulation of circadian biology, and
      metabolic pathways. Additionally, 1 may serve as a starting point for design of
      Rev-erbalpha chemical probes with in vivo pharmacological activity.

PMID- 20677823
TI  - Carbonylative polymerization of propylene oxide: a multicatalytic approach to the
      synthesis of poly(3-hydroxybutyrate).
AB  - We report a highly efficient method for the synthesis of poly(3-hydroxybutyrate)
      by the carbonylative polymerization of propylene oxide. The use of compatible
      epoxide carbonylation and lactone polymerization catalysts allows for a one-pot
      reaction that eliminates the need to isolate and purify the toxic beta
      butyrolactone intermediate.

PMID- 20677824
TI  - Organocatalysis in cross-coupling: DMEDA-catalyzed direct C-H arylation of
      unactivated benzene.
AB  - A striking breakthrough to the frame of traditional cross-couplings/C-H
      functionalizations using an organocatalyst remains unprecedented. We uncovered a
      conceptually different approach toward the biaryl syntheses by using DMEDA as the
      catalyst to promote the direct C-H arylation of unactivated benzene in the
      presence of potassium tert-butoxide. The arylation of unactivated benzene with
      aryl iodides, or aryl bromides and even chlorides under the assistance of an iodo
      group, could simply take place at 80  degrees C. The new methodology presumably
      involves an aryl radical anion as an intermediate. This finding offers an option
      toward establishing a new horizon for direct C-H/cross-coupling reactions.

PMID- 20677825
TI  - Depletion of abundant plasma proteins and limitations of plasma proteomics.
AB  - Immunoaffinity depletion with antibodies to the top 7 or top 14 high-abundance
      plasma proteins is used to enhance detection of lower abundance proteins in both
      shotgun and targeted proteomic analyses. We evaluated the effects of top 7/top 14
      immunodepletion on the shotgun proteomic analysis of human plasma. Our goal was
      to evaluate the impact of immunodepletion on detection of proteins across
      detectable ranges of abundance. The depletion columns afforded highly repeatable
      and efficient plasma protein fractionation. Relatively few nontargeted proteins
      were captured by the depletion columns. Analyses of unfractionated and
      immunodepleted plasma by peptide isoelectric focusing (IEF), followed by liquid
      chromatography-tandem mass spectrometry (LC-MS/MS), demonstrated enrichment of
      nontargeted plasma proteins by an average of 4-fold, as assessed by MS/MS
      spectral counting. Either top 7 or top 14 immunodepletion resulted in a 25%
      increase in identified proteins compared to unfractionated plasma. Although 23
      low-abundance (<10 ng mL(-1)) plasma proteins were detected, they accounted for
      only 5-6% of total protein identifications in immunodepleted plasma. In both
      unfractionated and immunodepleted plasma, the 50 most abundant plasma proteins
      accounted for 90% of cumulative spectral counts and precursor ion intensities,
      leaving little capacity to sample lower abundance proteins. Untargeted proteomic
      analyses using current LC-MS/MS platforms-even with immunodepletion-cannot be
      expected to efficiently discover low-abundance, disease-specific biomarkers in
      plasma.

PMID- 20677830
TI  - A 1.9 A crystal structure of the HDV ribozyme precleavage suggests both Lewis
      acid and general acid mechanisms contribute to phosphodiester cleavage.
AB  - The hepatitis delta virus (HDV) ribozyme and HDV-like ribozymes are self-cleaving
      RNAs found throughout all kingdoms of life. These RNAs fold into a double-nested
      pseudoknot structure and cleave RNA, yielding 2',3'-cyclic phosphate and 5'
      hydroxyl termini. The active site nucleotide C75 has a pK(a) shifted >2 pH units
      toward neutrality and has been implicated as a general acid/base in the cleavage
      reaction. An active site Mg(2+) ion that helps activate the 2'-hydroxyl for
      nucleophilic attack has been characterized biochemically; however, this ion has
      not been visualized in any previous structures. To create a snapshot of the
      ribozyme in a state poised for catalysis, we have crystallized and determined the
      structure of the HDV ribozyme bound to an inhibitor RNA containing a
      deoxynucleotide at the cleavage site. This structure includes the wild-type C75
      nucleotide and Mg(2+) ions, both of which are required for maximal ribozyme
      activity. This structure suggests that the position of C75 does not change during
      the cleavage reaction. A partially hydrated Mg(2+) ion is also found within the
      active site where it interacts with a newly resolved G.U reverse wobble. Although
      the inhibitor exhibits crystallographic disorder, we modeled the ribozyme
      substrate complex using the conformation of the inhibitor strand observed in the
      hammerhead ribozyme. This model suggests that the pro-R(P) oxygen of the scissile
      phosphate and the 2'-hydroxyl nucleophile are inner-sphere ligands to the active
      site Mg(2+) ion. Thus, the HDV ribozyme may use a combination of metal ion Lewis
      acid and nucleobase general acid strategies to effect RNA cleavage.

PMID- 20677826
TI  - Plasma proteomic analysis of simian immunodeficiency virus infection of rhesus
      macaques.
AB  - Lentiviral replication in its target cells affects a delicate balance between
      cellular cofactors required for virus propagation and immunoregulation for host
      defense. To better elucidate cellular proteins linked to viral infection, we
      tested plasma from rhesus macaques infected with the simian immunodeficiency
      viral strain SIVsmm9, prior to, 10 days (acute), and 49 weeks (chronic) after
      viral infection. Changes in plasma protein content were measured by quantitative
      mass spectrometry by isobaric tags for absolute and relative quantitation (iTRAQ)
      methods. An 81 and 232% increase in SERPINA1 was seen during acute and chronic
      infection, respectively. Interestingly, gelsolin, vitamin D binding protein and
      histidine rich glycoprotein were decreased by 45% in acute conditions but
      returned to baseline during chronic infection. When compared to uninfected
      controls, a 48-103% increase in leucine rich alpha 2-glycoprotein, vitronectin,
      and ceruloplasmin was observed during chronic viral infection. Observed changes
      in plasma proteins expression likely represent a compensatory host response to
      persistent viral infection.

PMID- 20677832
TI  - The PHD3 domain of MLL acts as a CYP33-regulated switch between MLL-mediated
      activation and repression .
AB  - The mixed lineage leukemia (MLL) gene plays a critical role in epigenetic
      regulation of gene expression and is a frequent target of chromosomal
      translocations leading to leukemia. MLL plant homeodomain 3 (PHD3) is lost in all
      MLL translocation products, and reinsertion of PHD3 into MLL fusion proteins
      abrogates their transforming activity. PHD3 has been shown to interact with the
      RNA-recognition motif (RRM) domain of human nuclear Cyclophilin33 (CYP33). Here,
      we show that CYP33 mediates downregulation of the expression of MLL target genes
      HOXC8, HOXA9, CDKN1B, and C-MYC, in a proline isomerase-dependent manner. This
      downregulation correlates with the reduction of trimethylated lysine 4 of histone
      H3 (H3K4me3) and histone H3 acetylation. We have structurally characterized both
      the PHD3 and CYP33 RRM domains and analyzed their binding to one another. The
      PHD3 domain binds H3K4me3 (preferentially) and the CYP33 RRM domain at distinct
      sites. Our binding data show that binding of H3K4me3 to PHD3 and binding of the
      CYP33 RRM domain to PHD3 are mutually inhibitory, implying that PHD3 is a
      molecular switch for the transition between activation and repression of target
      genes. To explore the possible mechanism of CYP33/PHD3-mediated repression, we
      have analyzed the CYP33 proline isomerase activity on various H3 and H4 peptides
      and shown selectivity for two sites in H3. Our results provide a possible
      mechanism for the MLL PHD3 domain to act as a switch between activation and
      repression.

PMID- 20677831
TI  - Solution structure and membrane binding of the toxin fst of the par addiction
      module.
AB  - The par toxin-antitoxin system is required for the stable inheritance of the
      plasmid pAD1 in its native host Enterococcus faecalis. It codes for the toxin Fst
      and a small antisense RNA which inhibits translation of toxin mRNA, and it is the
      only known antisense regulated toxin-antitoxin system in Gram-positive bacteria.
      This study presents the structure of the par toxin Fst, the first atomic
      resolution structure of a component of an antisense regulated toxin-antitoxin
      system. The mode of membrane binding was determined by relaxation enhancements in
      a paramagnetic environment and molecular dynamics simulation. Fst forms a
      membrane-binding alpha-helix in the N-terminal part and contains an intrinsically
      disordered region near the C-terminus. It binds in a transmembrane orientation
      with the C-terminus likely pointing toward the cytosol. Membrane-bound, alpha
      helical peptides are frequently found in higher organisms as components of the
      innate immune system. Despite similarities to these antimicrobial peptides, Fst
      shows neither hemolytic nor antimicrobial activity when applied externally to a
      series of bacteria, fungal cells, and erythrocytes. Moreover, its charge
      distribution, orientation in the membrane, and structure distinguish it from
      antimicrobial peptides.

PMID- 20677833
TI  - Structure-activity relationship analysis of peptides targeting the EphA2
      receptor.
AB  - The EphA2 receptor tyrosine kinase has emerged as a promising new therapeutic
      target in cancer because of its high level of expression in tumors. EphA2
      specific antibodies have been used to deliver drugs and toxins to tumor cells,
      leading to inhibition of tumor growth and metastatic dissemination. We previously
      identified two related peptides, YSA and SWL, that selectively bind to the ligand
      binding domain of EphA2 but not other Eph receptors and could therefore be useful
      as selective targeting agents. Here we characterize the two peptides and a series
      of derivatives. On the basis of systematic amino acid replacements, only five YSA
      residues appear to be critical for high-affinity receptor binding. Furthermore, a
      peptide comprising only the first five residues of YSA retains selectivity for
      EphA2. Similar to ephrin-A1, the physiological ligand for EphA2, both YSA and SWL
      activate EphA2 and inhibit downstream oncogenic signaling pathways in PC3 cancer
      cells. The two peptides and derivatives are quite stable in conditioned cell
      culture medium and show promise for delivering drugs and imaging agents to EphA2
      expressing tumors.

PMID- 20677834
TI  - How things fall apart: understanding the nature of internalizing through its
      relationship with impairment.
AB  - The literature suggests that internalizing psychopathology relates to impairment
      incrementally and gradually. However, the form of this relationship has not been
      characterized. This form is critical to understanding internalizing
      psychopathology, as it is possible that internalizing may accelerate in effect at
      some level of severity, defining a natural boundary of abnormality. Here, a novel
      method-semiparametric structural equation modeling-was used to model the
      relationship between internalizing and impairment in a sample of 8,580
      individuals from the 2000 British Office for National Statistics Survey of
      Psychiatric Morbidity, a large, population-representative study of
      psychopathology. This method allows one to model relationships between latent
      internalizing and impairment without assuming any particular form a priori and to
      compare models in which the relationship is constant and linear. Results suggest
      that the relationship between internalizing and impairment is in fact linear and
      constant across the entire range of internalizing variation and that it is
      impossible to nonarbitrarily define a specific level of internalizing beyond
      which consequences suddenly become catastrophic in nature. Results demonstrate
      the phenomenological continuity of internalizing psychopathology, highlight the
      importance of impairment as well as symptoms, and have clear implications for
      defining mental disorder.

PMID- 20677835
TI  - The early course of depression: a longitudinal investigation of prodromal
      symptoms and their relation to the symptomatic course of depressive episodes.
AB  - The present study explored longitudinal evidence for prodromal symptoms of
      depression episodes. A model based on previous findings of the relations between
      prodromal and residual symptoms was described and used to generate hypotheses
      tested in this study. Data were analyzed from 160 participants from the Cognitive
      Vulnerability to Depression (CVD) project (L. Alloy & L. Abramson, 1999) who
      experienced an episode of depression during the prospective follow-up period and
      60 CVD participants who did not. Congruent with the hypothesis, individuals who
      subsequently developed an episode of depression experienced significantly greater
      numbers of depression symptoms in the period of time leading up to the acute
      episode compared with those who did not develop a depressive episode. Seven
      depression symptoms were particularly likely to appear before the onset of an
      acute episode. Furthermore, all 3 predictions from the model were supported: the
      durations of prodromal and residual phases were correlated, the prodromal and
      residual symptom profiles were quite similar, and the order of symptom onset was
      significantly and highly negatively correlated with the order of symptom
      remission. Additionally, residual symptom profiles were similar to subsequent
      prodromal symptom profiles in individuals who experienced more than 1 depressive
      episode. These findings are discussed in terms of the importance of understanding
      the earliest prodromal symptoms to appear and their relation to the symptomatic
      course of depression episodes. Implications for early intervention are also
      discussed.

PMID- 20677836
TI  - Temperamental emotionality in preschool-aged children and depressive disorders in
      parents: associations in a large community sample.
AB  - Researchers and clinicians have long hypothesized that there are temperamental
      vulnerabilities to depressive disorders. Despite the fact that individual
      differences in temperament should be evident in early childhood, most studies
      have focused on older youth and adults. We hypothesized that if early childhood
      temperament is a risk factor for depressive disorders, it should be associated
      with better established risk markers, such parental depression. Hence, we
      examined the associations of laboratory-assessed positive emotionality (PE),
      negative emotionality (NE), and behavioral inhibition (BI) with semistructured
      interview-based diagnoses of parental depressive disorders in a community sample
      of 536 3-year old children. Children with higher levels of NE and BI had higher
      probabilities of having a depressed parent. However, both main effects were
      qualified by interactions with child PE. At high and moderate (but not low)
      levels of child PE, greater NE and BI were associated with higher rates of
      parental depression. Conversely, at low (but not high and moderate) levels of
      child NE, low PE was associated with higher rates of parental depression. Child
      temperament was not associated with parental anxiety and substance use disorders.
      These findings indicate that laboratory-assessed temperament in young children is
      associated with parental depressive disorders; however, the relations are
      complex, and it is important to consider interactions between temperament
      dimensions rather than focusing exclusively on main effects.

PMID- 20677837
TI  - When distress does not become depression: emotion context sensitivity and
      adjustment to bereavement.
AB  - Recent evidence suggests that the sensitivity of emotion responses to changing
      context may be a key element of psychological adjustment and psychopathology
      (Bonanno et al., 2007; Rottenberg, Kasch, Gross, & Gotlib, 2002). However, there
      have been no previous investigations to examine emotion context sensitivity and
      adjustment following stressful life events. This investigation addressed this
      deficit in a sample of middle-aged bereaved adults (N = 48) whose emotion
      responses were measured as they described loss and non-loss-related events during
      a laboratory interview 4 months after the death of their spouse or child.
      Symptoms of depression were assessed using structured clinical interviews at 4
      and 18 months postloss. Although positive emotions were beneficial regardless of
      context, context sensitivity for negative emotions at 4 months predicted fewer
      depression symptoms at 18 months. These findings suggest that the capacity to
      shift negative emotion responses according to changing context may differentiate
      those individuals who will show improvements in depression symptoms over time
      from those who will show chronic impairments. Implications for future research
      and clinical intervention are discussed.

PMID- 20677838
TI  - Selective attention to affective stimuli and clinical depression among youths:
      role of anxiety and specificity of emotion.
AB  - Cognitive models of psychopathology posit that the content or focus of
      information-processing biases (e.g., attentional biases) is disorder specific:
      Depression is hypothesized to be characterized by attentional biases specifically
      for depression-relevant stimuli (e.g., sad facial expressions), whereas anxiety
      should relate particularly to attentional biases to threat-relevant stimuli
      (e.g., angry faces). However, little research has investigated this specificity
      hypothesis and none with a sample of youths. The present study examined
      attentional biases to emotional faces (sad, angry, and happy compared with
      neutral) in groups of pure depressed, pure anxious, comorbid depressed and
      anxious, and control youths (ages 9-17 years; N = 161). Consistent with cognitive
      models, pure depressed and pure anxious youths exhibited attentional biases
      specifically to sad and angry faces, respectively, whereas comorbid youths
      exhibited attentional biases to both facial expressions. In addition, control
      youths exhibited attentional avoidance of sad faces, and comorbid boys avoided
      happy faces. Overall, findings suggest that cognitive biases and processing of
      particular emotional information are specific to pure clinical depression and
      anxiety, and results inform etiological models of potentially specific processes
      that are associated with internalizing disorders among youths.

PMID- 20677839
TI  - Resting frontal EEG asymmetry as an endophenotype for depression risk: sex
      specific patterns of frontal brain asymmetry.
AB  - Resting frontal electroencephalographic (EEG) asymmetry has been hypothesized as
      a marker of risk for major depressive disorder (MDD), but the extant literature
      is based predominately on female samples. Resting frontal asymmetry was assessed
      on 4 occasions within a 2-week period in 306 individuals aged 18-34 (31% male)
      with (n = 143) and without (n = 163) lifetime MDD as defined by the Diagnostic
      and Statistical Manual of Mental Disorders, 4th edition (American Psychiatric
      Association, 1994). Lifetime MDD was linked to relatively less left frontal
      activity for both sexes using a current source density (CSD) reference, findings
      that were not accounted for solely by current MDD status or current depression
      severity, suggesting that CSD-referenced EEG asymmetry is a possible
      endophenotype for depression. In contrast, results for average and linked mastoid
      references were less consistent but demonstrated a link between less left frontal
      activity and current depression severity in women.

PMID- 20677840
TI  - Refining the tobacco dependence phenotype using the Wisconsin Inventory of
      Smoking Dependence Motives: II. Evidence from a laboratory self-administration
      assay.
AB  - Prior analyses of the Wisconsin Inventory of Smoking Dependence Motives (Piper et
      al., 2004) implicated 4 subscales as primary dependence motives (PDM) indexing
      the core features of tobacco dependence, with the remaining subscales reflecting
      secondary dependence motives (SDM; Piper et al., 2008). The current study
      extended this work by examining the correlates of PDM, SDM, their subscales, and
      other indicators of dependence in an operant self-administration paradigm.
      Smokers (N = 58) worked for cigarette puffs under differing fixed ratio
      schedules. Analyses focused on predicting self-administration under conditions of
      minimal constraint on tobacco access and on withdrawal and craving under
      conditions of severe constraint. Results support a 2-factor model of dependence,
      with the PDM factor showing relatively stronger relations with tobacco self
      administration and the SDM factor showing relatively stronger relations with
      withdrawal symptomatology and distress-related craving. The PDM appears to index
      core features of tobacco dependence, but susceptibility to deprivation-contingent
      distress and craving may be better indexed by SDM.

PMID- 20677841
TI  - Effects of expectancies and coping on pain-induced motivation to smoke.
AB  - The prevalence of tobacco smoking among persons with recurrent pain is
      approximately twice that observed in the general population. Smoking has been
      associated with the development and exacerbation of several chronically painful
      conditions. Conversely, there is both experimental and cross-sectional evidence
      that pain is a potent motivator of smoking. A recent study provided the first
      evidence that laboratory-induced pain could elicit increased craving and produce
      shorter latencies to smoke (Ditre & Brandon, 2008). To further elucidate
      interrelations between pain and smoking, and to identify potential targets for
      intervention, in the current study, we tested whether several constructs derived
      from social-cognitive theory influence the causal pathway between pain and
      increased motivation to smoke. Smokers (N = 132) were randomly assigned to 1 of 4
      conditions in this 2 x 2 between-subjects experimental design. Results indicated
      that manipulations designed to (a) challenge smoking-related outcome expectancies
      for pain reduction and (b) enhance pain-related coping produced decreased urge
      ratings and increased latencies to smoke, relative to controls. An unexpected
      interaction effect revealed that although each manipulation was sufficient to
      reduce smoking urges, the combination was neither additive nor synergistic. These
      findings were integrated with those of the extant literature to conceptualize and
      depict a causal pathway between pain and motivation to smoke as moderated by
      smoking-related outcome expectancies and mediated by the use of pain coping
      behaviors.

PMID- 20677842
TI  - The role of contextual risk, impulsivity, and parental knowledge in the
      development of adolescent antisocial behavior.
AB  - The present study (a) tests main and moderational effects of neighborhood and
      family risk, and adolescent impulsivity on the development of male and female
      antisocial behavior (ASB) and (b) examines the extent to which these effects work
      indirectly through parental knowledge. Adolescents (N = 4,597; 51% male) reported
      on informal social control in their neighborhoods, their family types, and
      impulsivity at age 12, and on parental monitoring and ASB at ages 13 and 15
      years. Neighborhoods were further defined as risk and nonrisk in economic
      deprivation by census-level data. Main effects of neighborhood risk, single
      parenthood, and impulsivity on ASB were found for male and female adolescents.
      For female adolescents, impulsivity interacted with neighborhood economic
      deprivation and with family type in the prediction of parental knowledge.
      Impulsivity and contextual risk factors in part increased adolescent ASB through
      decreasing parental knowledge. Theoretical and policy implications are discussed.

PMID- 20677843
TI  - Morphological alterations in the prefrontal cortex and the amygdala in
      unsuccessful psychopaths.
AB  - Although deficits in several cortical and subcortical structures have been found
      in psychopaths, it remains unclear whether the neuropathology differs between
      subgroups of psychopaths (i.e., unsuccessful and successful). Using both
      traditional and novel image analyses methods, this study aims to reveal gross and
      subtle morphological changes in the prefrontal cortex and the amygdala in
      unsuccessful and successful psychopaths. Volumetric segmentation, cortical
      pattern matching, and surface-based mesh modeling methods were used to examine
      prefrontal and amygdala structures in 16 unsuccessful psychopaths, 10 successful
      psychopaths, and 27 controls. Significant reduced gray matter volume and cortical
      thickness/surface shape in the middle frontal, orbitofrontal cortex and the
      amygdala were found in unsuccessful psychopaths but not successful psychopaths,
      compared with controls. This study provides the first evidence of greater
      prefrontal and amygdala structural deficits in unsuccessful psychopaths, which
      may predispose them to poor behavioral control and impaired decision-making, thus
      making them more prone to convictions.

PMID- 20677844
TI  - An actor-partner interdependence model of spousal criticism and depression.
AB  - Although perceived criticism is relational, most theory and research concerns
      only relatives' criticism toward patients and not the converse. With a sample of
      33 depressed patients and their spouses, we take a fully relational approach to
      criticism by testing an actor-partner interdependence model (Kenny, Kashy, &
      Cook, 2006). Patient intended criticism was especially strongly associated with
      depressive symptoms for wives, whereas patient perceived criticism was especially
      negatively related to depressive symptoms for husbands. Nondepressed partner
      intended criticism was positively related to patient depressive symptoms, but
      nondepressed wife perceived criticism was negatively related to husband
      depressive symptoms. The importance of including patient intended and partner
      perceived criticism as well as examining sex differences in models of criticism
      and depression are discussed.

PMID- 20677845
TI  - Subtypes of partner violence perpetrators among male and female psychiatric
      patients.
AB  - The goal of this naturalistic study was to examine heterogeneity among female and
      male civil psychiatric patients with a history of intimate partner violence (IPV)
      perpetration. Participants were 567 patients drawn from the MacArthur Violence
      Risk Assessment Study (J. Monahan et al., 2001). The authors examined subtype
      composition among 138 women and 93 men with positive histories of IPV and
      compared these groups with 111 women and 225 men with no histories of IPV.
      Findings for men and women were consistent with reports from studies of male
      perpetrators in forensic and community settings in that generally
      violent/antisocial, borderline/dysphoric, and family only/low-psychopathology
      subtypes of perpetrators were identified in both men and women. This study
      provides preliminary evidence for the generalizability of typologies derived from
      nonpsychiatric partner violence perpetrators to psychiatric populations and
      suggests that typologies derived from studies of male IPV perpetrators may
      provide useful guidance for the investigation of female IPV perpetration.

PMID- 20677846
TI  - A body-related dot-probe task reveals distinct attentional patterns for bulimia
      nervosa and anorexia nervosa.
AB  - We investigated body-related attentional biases in eating disorders by testing
      whether individuals with anorexia nervosa (AN, n = 19) and bulimia nervosa (BN, n
      = 18) differ from healthy controls (HC, n = 21) in their bias for attending to a
      photo of their own body (self-photo) relative to a photo of a matched control
      participant's body (other photo). In a modified dot-probe task, self- and other
      photos served as cues on the left and the right of the screen. After 1 of 2 time
      intervals, 1 of the photos was singled out by a surrounding frame, and
      participants had to saccade toward it. Saccade latency was used as an index of
      covert attention to the cue photos. In the AN group, saccades were faster when
      the self-photo was the target than when the other photo was the target. In the BN
      group, there was a numerically opposite but nonsignificant pattern. Cues did not
      affect saccade latencies in healthy controls. The bias for self-photos correlated
      with body dissatisfaction in the AN group. This is the first evidence of an
      attentional bias for self-photos over other photos in the AN group and for
      fundamental attentional differences between AN and BN.

PMID- 20677847
TI  - When doors of perception open: visual contrast sensitivity in never-medicated,
      first-episode schizophrenia.
AB  - Schizophrenia is characterized by impaired visual contrast sensitivity and
      anomalous perceptual experiences. The aim of this study was to investigate these
      phenomena in unmedicated patients with first-episode schizophrenia. Visual
      contrast sensitivity was measured with pulsed-pedestal and steady-pedestal tests,
      which bias information processing toward the parvocellular and magnocellular
      pathways, respectively. Anomalous perceptual experiences were investigated with
      the Structured Interview for Assessing Perceptual Anomalies (SIAPA). Results
      revealed that patients with schizophrenia (n = 20) exhibited increased contrast
      sensitivity values on the magnocellular test relative to the control participants
      (n = 20). In the parvocellular condition, there was no significant difference
      between the two groups. The higher magnocellular contrast sensitivity values were
      associated with increased visual SIAPA scores, especially at the two lowest
      spatial frequencies (0.25 and 0.5 cycles/degree). These results indicate the
      heightened sensitivity of magnocellular pathways in unmedicated first-episode
      schizophrenia, which may contribute to anomalous perceptual experiences and
      sensory overloading.

PMID- 20677848
TI  - Early attentional deficits in an attention-to-prepulse paradigm in ADHD adults.
AB  - Adults with attention-deficit/hyperactivity disorder (ADHD) were examined for
      early and late attentional processes as a function of controlled attention. The
      test paradigm was the attentional modulation of prepulse inhibition (PPI; early
      controlled attentional processing) and prepulse facilitation (PPF; late
      controlled attentional processing). In 49 patients and 49 controls, the authors
      measured acoustic startle responses to 96-dB startle pulses preceded 120, 240
      (for PPI), 2,000, and 4,500 (for PPF) ms by a 68-dB prepulse noise. Geometric
      figures signaled that prepulses were to be ignored or attended to (automatic vs.
      controlled attention). ADHD patients exhibited deficits in prepulse modulation,
      but these reflected an interaction of controlled attention and time of
      information processing. Normal PPI and PPF occurred under all conditions except
      for controlled attentional modulation of PPI. Attention deficits in ADHD patients
      may reflect not general derangements in information processing or ability to
      attend but, rather, selective disturbances of controlled attention during early
      information processing.

PMID- 20677849
TI  - Serotonin transporter gene associations with psychopathic traits in youth vary as
      a function of socioeconomic resources.
AB  - Although prior research has examined the genetic correlates of antisocial
      behavior, molecular genetics influences on psychopathic traits remain largely
      unknown. Consequently, we investigated the influence of polymorphic variation at
      the serotonin transporter protein gene (SLC6A4) and socioeconomic resources (SES)
      on psychopathic traits in youth across two distinct samples in two separate
      studies. In Study 1, a main effect of serotonin transporter (5-HTTLPR) genotype
      was associated with the impulsivity dimension of psychopathy. That is,
      individuals homozygous for the short allele evidenced more impulsivity than did
      those homozygous for the long allele. In contrast, a gene-environment interaction
      was associated with the callous-unemotional and narcissistic features of
      psychopathy. Callous-unemotional and narcissistic traits increased as SES
      decreased only among youths with the homozygous-long (l/l) genotype, a novel
      finding replicated and extended in Study 2. These studies provide preliminary
      results that the l/l genotype confers risk for the emotional deficits and
      predatory interpersonal traits associated with psychopathy among youths raised in
      disadvantaged environments.

PMID- 20677850
TI  - Increased rates of events that activate or deactivate the behavioral approach
      system, but not events related to goal attainment, in bipolar spectrum disorders.
AB  - Research indicates that life events involving goal attainment and goal striving
      trigger hypomania/mania and that negative life events trigger bipolar depression.
      These findings are consistent with the behavioral approach system (BAS)
      dysregulation model of bipolar disorders, which suggests that individuals with
      bipolar disorders are hypersensitive to cues signaling opportunity for reward and
      cues signaling failure and loss of rewards. However, no studies to date have
      investigated whether individuals with bipolar spectrum disorders experience
      increased rates of these BAS-relevant life events, which would place them at
      double risk for developing bipolar episodes. The present study found that
      individuals with bipolar II disorder and cyclothymia experience increased rates
      of BAS-activating and BAS-deactivating, but not goal-attainment, life events.
      Finally, for bipolar spectrum individuals only, BAS-activating events predicted
      BAS-deactivating events' rates.

PMID- 20677851
TI  - Attentional bias toward suicide-related stimuli predicts suicidal behavior.
AB  - A long-standing challenge for scientific and clinical work on suicidal behavior
      is that people often are motivated to deny or conceal suicidal thoughts. The
      authors proposed that people considering suicide would possess an objectively
      measurable attentional bias toward suicide-related stimuli and that this bias
      would predict future suicidal behavior. Participants were 124 adults presenting
      to a psychiatric emergency department who were administered a modified emotional
      Stroop task and followed for 6 months. Suicide attempters showed an attentional
      bias toward suicide-related words relative to neutral words, and this bias was
      strongest among those who had made a more recent attempt. Importantly, this
      suicide-specific attentional bias predicted which people made a suicide attempt
      over the next 6 months, above and beyond other clinical predictors. Attentional
      bias toward more general negatively valenced words did not predict any suicide
      related outcomes, supporting the specificity of the observed effect. These
      results suggest that suicide-specific attentional bias can serve as a behavioral
      marker for suicidal risk, and ultimately improve scientific and clinical work on
      suicide-related outcomes.

PMID- 20677852
TI  - Co-occurrence of avoidant personality disorder and child sexual abuse predicts
      poor outcome in long-standing eating disorder.
AB  - Few consistent predictive factors for eating disorder have been identified across
      studies. In the current 5-year prospective study, the objective was to examine
      whether (a) personality disorder and child sexual abuse predict the course of
      severity of eating disorder symptoms after inpatient treatment and (b) how the
      predictors interact. A total of 74 patients with long-standing eating disorder
      and mean age of 30 years were assessed at the beginning and end of inpatient
      therapy and at 1-, 2-, and 5-year follow-up. A mixed model was used to examine
      the predictors. Avoidant personality disorder and child sexual abuse interacted
      in predicting high levels of eating disorder over a long-term course. These
      results suggest that eating disorder, avoidant personality disorder, and sequelae
      after child sexual abuse are potential targets for treatment that need further
      investigation.

PMID- 20677855
TI  - Causal inference and developmental psychology.
AB  - Causal inference is of central importance to developmental psychology. Many key
      questions in the field revolve around improving the lives of children and their
      families. These include identifying risk factors that if manipulated in some way
      would foster child development. Such a task inherently involves causal inference:
      One wants to know whether the risk factor actually causes outcomes. Random
      assignment is not possible in many instances, and for that reason, psychologists
      must rely on observational studies. Such studies identify associations, and
      causal interpretation of such associations requires additional assumptions.
      Research in developmental psychology generally has relied on various forms of
      linear regression, but this methodology has limitations for causal inference.
      Fortunately, methodological developments in various fields are providing new
      tools for causal inference-tools that rely on more plausible assumptions. This
      article describes the limitations of regression for causal inference and
      describes how new tools might offer better causal inference. This discussion
      highlights the importance of properly identifying covariates to include (and
      exclude) from the analysis. This discussion considers the directed acyclic graph
      for use in accomplishing this task. With the proper covariates having been
      chosen, many of the available methods rely on the assumption of "ignorability."
      The article discusses the meaning of ignorability and considers alternatives to
      this assumption, such as instrumental variables estimation. Finally, the article
      considers the use of the tools discussed in the context of a specific research
      question, the effect of family structure on child development.

PMID- 20677854
TI  - A mixture-model approach to linking ADHD to adolescent onset of illicit drug use.
AB  - Prior research findings have been mixed as to whether attention
      deficit/hyperactivity disorder (ADHD) is related to illicit drug use independent
      of conduct problems (CP). With the current study, the authors add to this
      literature by investigating the association between trajectories of ADHD symptoms
      across childhood and adolescence and onset of illicit drug use, with and without
      controlling for CP. In a longitudinal panel study of a community sample of 754
      girls and boys recruited in kindergarten, this research question was examined
      with a combination of growth mixture modeling (to model parent-reported ADHD
      symptom trajectories) and survival analysis (to model youth-reported initiation
      of illicit drug use). Results revealed a 3-class model of ADHD trajectories, with
      1 class exhibiting no or minimal symptoms throughout childhood and adolescence,
      another class showing a convex shape (an increase, then a decrease in symptoms)
      across time, and a third class showing a concave shape (a decrease, then a slight
      increase in symptoms) over time. The concave-trajectory class demonstrated
      significantly earlier onset of illicit drug use than the minimal-problem class,
      with the convex-trajectory class falling between (but not significantly different
      from either of the other two classes). These results did not change when the
      authors added CP to the model as a covariate. Implications of findings for theory
      and practice are discussed.

PMID- 20677856
TI  - Learning to read and spell in Persian: a cross-sectional study from Grades 1 to
      4.
AB  - We investigated the reading and spelling development of 140 Persian children
      attending Grades 1-4 in Iran. Persian has very consistent letter-sound
      correspondences, but it varies in transparency because 3 of its 6 vowel phonemes
      are not marked with letters. Persian also varies in spelling consistency because
      6 phonemes have more than one orthographic representation. We tested whether
      lexicality effects-an advantage of words over nonwords-would be affected be
      reading transparency and spelling consistency. We found that children became more
      efficient readers and spellers across grades, with the greatest growth occurring
      between Grades 1 and 2. For reading, lexicality effects were present with
      transparent words starting in Grade 2, but lexicality effects with opaque words
      were not yet present in Grade 4. As expected, the size of transparency effects
      for reading decreased across grades. For spelling, however, there was no
      lexicality effect for either consistent or inconsistent words. Moreover,
      consistency effects were large and did not decrease systematically across grades.
      Most interesting from a developmental perspective was the finding that both
      reading transparency and spelling polygraphy affected reading as well as spelling
      in Grades 1 and 2, but the word characteristics had differential effects as a
      function of literacy task in Grades 3 and 4. This pattern highlights the
      vulnerability of children's representations and processes during the early phases
      of acquisition as well as the rapidity with which representations and processes
      become specialized as a function of the literacy task at hand.

PMID- 20677857
TI  - Longitudinal outcomes of young high-risk adolescents with imaginary companions.
AB  - The creation and cultivation of an imaginary companion is considered to be a
      healthy form of pretend play in early childhood, but there tends to be a less
      positive view of older children who have them. To test the extent that having an
      imaginary companion in middle school is associated with positive or negative
      outcomes, an ethnically diverse sample of 152 middle school children at high risk
      for developing problem behaviors were interviewed about imaginary companions,
      coping styles, and problem behaviors. Although having a current imaginary
      companion (n = 13) was associated with using more positive coping strategies,
      peer nomination data indicated that these children had low social preference with
      peers. In addition, our data indicated that these children were perceived by
      their parents as having more problem behaviors compared with young adolescents
      who never had imaginary companions (n = 108) or children who had imaginary
      companions in the past (n = 31). However, a longitudinal follow-up at the end of
      high school indicated that the children who had imaginary companions in middle
      school showed greater positive adjustment on a multiple-indicator adjustment
      construct.

PMID- 20677858
TI  - Adolescents' exposure to sexy media does not hasten the initiation of sexual
      intercourse.
AB  - It is widely believed that exposure to sexy content in the mass media leads
      teenagers to become sexually active. Although most research linking sexy media
      exposure to adolescents' sexual behavior is cross-sectional, several recent, well
      publicized longitudinal studies purport to find a causal connection, which has
      alarmed the public and prompted criticism of the entertainment industry for its
      corrupting influence on youth. One problem in research on media effects on sexual
      activity, however, is that outcomes that are presumed to result from media
      exposure may actually be due to factors that differentially predispose
      adolescents to have different degrees of media exposure and are themselves
      related to sexual activity. We reanalyzed data from one of these longitudinal
      studies (Brown et al., 2006) using propensity score matching to control for
      preexisting differences between adolescents with and without high exposure to
      sexy media. With such controls for differential selection in place, we found no
      evidence that the initiation of sexual intercourse is hastened by exposure to
      sexy media.

PMID- 20677859
TI  - Preschoolers' understanding of others' desires: fulfilling mine enhances my
      understanding of yours.
AB  - We developed a gift-giving task requiring children to identify their mother's
      desire, when her desire differed from theirs. We found a developmental change: 3-
      and 4-year-olds performed more poorly than 5-year-olds (Experiment 1). A modified
      version of this task (Experiment 2) revealed that 3-, 4-, and 5-year-olds whose
      desires had been fulfilled chose an appropriate gift for their mothers
      significantly more often than children whose desires were unfulfilled. Children
      who merely anticipated desire fulfillment also outperformed children whose
      desires were unfulfilled. Analysis of children's verbal explanations provides
      converging evidence that desire fulfillment enhanced children's tendency to adopt
      the perspective of their mother and justify their choices by referencing her
      desires. Discussion focuses on why desire fulfillment enhances children's ability
      to consider the desires of others.

PMID- 20677860
TI  - Associations among family environment, sustained attention, and school readiness
      for low-income children.
AB  - In this study, we examined the developmental pathways from children's family
      environment to school readiness within a low-income sample (N = 1,046), with a
      specific focus on the role of sustained attention. Six distinct factors of the
      family environment representing maternal parenting behaviors, the physical home
      environment, and maternal mental health at 3 years of age were explored as
      independent predictors of children's observed sustained attention as well as
      cognitive and behavioral outcomes at 5 years of age. Children were grouped by
      poverty status (poor vs. near-poor). Results suggest specificity in the
      associations among attention (focused attention and lack of impulsivity) and its
      correlates, with different patterns emerging by poverty status group. Overall,
      the family environment was largely unrelated to children's sustained attention.
      For both groups, focused attention was associated with receptive vocabulary;
      however, it partially mediated the association between maternal lack of hostility
      and receptive vocabulary only among the near-poor. In addition, lack of
      impulsivity was associated with both receptive vocabulary and externalizing
      behaviors but only for the poor group. Findings indicate sustained attention as a
      potential target for efforts aimed at enhancing school readiness among
      predominantly poor children.

PMID- 20677861
TI  - Why attend school? Chinese immigrant and European American preschoolers' views
      and outcomes.
AB  - The developing views of the purposes of school learning (PSLs) and related
      achievement among immigrant Chinese preschoolers and their European American (EA)
      age-mates were examined. Both culture and socioeconomic status (SES) were
      considered simultaneously, an often neglected research approach to studying Asian
      children. One hundred and fifty 4-year-olds-50 each of middle-class Chinese
      (CHM), low-income Chinese (CHL), and EA children-completed 2 story beginnings
      about school and were also tested for their language and math achievement.
      Results showed that 4-year-olds held sophisticated PSLs, ranging from
      intellectual to social and affect benefits. Large cultural and SES differences
      also emerged. CHM children mentioned more adult expectation and seriousness of
      learning than EA children who expressed more positive affect for self and
      compliance with adults. CHL children mentioned fewest PSLs. Achievement scores
      for oral expression of both immigrant groups were significantly lower than those
      of EA children despite similar reading and math achievement. Controlling for
      culture and SES, the authors found that children's articulated intellectual, but
      not other purposes, uniquely predicted their achievement in all tested domains.
      Cultural and SES influences on immigrant children are discussed.

PMID- 20677863
TI  - The "disgust face" conveys anger to children.
AB  - What does the "facial expression of disgust" communicate to children? When asked
      to label the emotion conveyed by different facial expressions widely used in
      research, children (N = 84, 4 to 9 years) were much more likely to label the
      "disgust face" as anger than as disgust, indeed just as likely as they were to
      label the "angry face" as anger. Shown someone with a disgust face and asked to
      generate a possible cause and consequence of that emotion, children provided
      answers indistinguishable from what they provided for an angry face--even for the
      minority who had labeled the disgust face as disgust. A majority of adults (N =
      22) labeled the same disgust faces shown to the children as disgust and generated
      causes and consequences that implied disgust.

PMID- 20677862
TI  - Developmental relations and patterns of change between alcohol use and number of
      sexual partners from adolescence through adulthood.
AB  - We explored two unanswered questions about the role of alcohol use in sexual
      behavior. First, we considered whether alcohol use temporally precedes and
      predicts changes in sexual behavior assessed as the number of sexual partners,
      whether the reverse pattern holds, or whether the association reflects a common,
      external cause. Second, we assessed whether associations between these behaviors
      change as adolescents transition to adulthood. These questions were addressed
      with a bivariate dual change latent difference score model. Drinking frequency
      and number of yearly sex partners were assessed 8 times across a 13-year period
      in a sample of 553 individuals. Assessment began when participants were in the
      9th grade (age: M = 15.11 years, SD = 0.43). In addition to an association
      between the individual growth trajectories of these behaviors, alcohol use was a
      leading indicator of changes in number of sex partners throughout adolescence,
      but the reverse pattern was not supported. Of importance, the predictive
      association could not be explained by individual differences in impulsivity,
      excitement seeking, conduct problems, hostility/aggression, conventional
      attitudes, gender, or divorce. Finally, in a developmentally meaningful pattern,
      alcohol use ceased to significantly predict changes in the number of sexual
      partners as adolescents transitioned to adulthood.

PMID- 20677864
TI  - Physiological down-regulation and positive emotion in marital interaction.
AB  - Previous studies have demonstrated that 1 function of positive emotion is the
      undoing of physiological arousal produced by negative emotions. These studies
      have used single-subject paradigms, in which emotions were induced by films in
      college-age individuals. In the present study, we examined the relationship
      between physiological down-regulation and positive emotion in a sample of 149
      middle-aged and older married couples engaged in a 15-min discussion of an area
      of marital conflict. During the conversation, autonomic and somatic physiological
      activity was measured, and emotional behaviors were recorded and subsequently
      coded. We found that during 20-s periods of down-regulation (where physiology
      transitioned from high arousal to low arousal), couples showed an increase in
      positive emotional behavior compared with periods without down-regulation. The
      finding was quite robust, suggesting that the undoing effect of positive emotion
      generalizes across age, sex, and marital satisfaction. The advantages of using
      positive emotion as an emotion regulation strategy are discussed.

PMID- 20677865
TI  - Attachment and emotion in school-aged children.
AB  - One of the primary functions of the attachment behavioral system is to regulate
      emotional experience under conditions of threat. Although research supports this
      association among infants and adults, few studies examine the relation between
      emotion and attachment in middle childhood. This study examined the concurrent
      associations among children's attachment organization and three indices of
      emotion reactivity/regulation: self- and parent-assessments of emotion,
      neuroendocrine reactivity, and fear-potentiated startle response. Ninety-seven 8-
      to 12-year-old children completed the Child Attachment Interview (CAI) and a fear
      potentiated startle paradigm on separate occasions, with salivary cortisol
      assessed before and after each assessment. Greater attachment security was
      related to greater child-reported positive trait- and state-level emotion, lower
      pre-CAI cortisol levels, higher initial startle magnitude during threat, and a
      faster decrease in startle magnitude during threat. The findings provide initial
      support that attachment security is related to select measures of emotion, though
      different methods of assessment yielded discrepant findings. The findings are
      discussed in terms of their contribution to theory and research examining
      attachment and emotion.

PMID- 20677866
TI  - Time course of processing emotional stimuli as a function of perceived emotional
      intelligence, anxiety, and depression.
AB  - An individual's self-reported abilities to attend to, understand, and reinterpret
      emotional situations or events have been associated with anxiety and depression,
      but it is unclear how these abilities affect the processing of emotional stimuli,
      especially in individuals with these symptoms. The present study recorded event
      related brain potentials while individuals reporting features of anxiety and
      depression completed an emotion-word Stroop task. Results indicated that anxious
      apprehension, anxious arousal, and depression were associated with self-reported
      emotion abilities, consistent with prior literature. In addition, lower anxious
      apprehension and greater reported emotional clarity were related to slower
      processing of negative stimuli indexed by event-related potentials (ERPs). Higher
      anxious arousal and reported attention to emotion were associated with ERP
      evidence of early attention to all stimuli regardless of emotional content.
      Reduced later engagement with stimuli was also associated with anxious arousal
      and with clarity of emotions. Depression was not differentially associated with
      any emotion processing stage indexed by ERPs. Research in this area may lead to
      the development of therapies that focus on minimization of anxiety to foster
      successful emotion regulation.

PMID- 20677867
TI  - Metacognitive emotion regulation: children's awareness that changing thoughts and
      goals can alleviate negative emotions.
AB  - Metacognitive emotion regulation strategies involve deliberately changing
      thoughts or goals to alleviate negative emotions. Adults commonly engage in this
      type of emotion regulation, but little is known about the developmental roots of
      this ability. Two studies were designed to assess whether 5- and 6-year-old
      children can generate such strategies and, if so, the types of metacognitive
      strategies they use. In Study 1, children described how story protagonists could
      alleviate negative emotions. In Study 2, children recalled times that they
      personally had felt sad, angry, and scared and described how they had regulated
      their emotions. In contrast to research suggesting that young children cannot use
      metacognitive regulation strategies, the majority of children in both studies
      described such strategies. Children were surprisingly sophisticated in their
      suggestions for how to cope with negative emotions and tailored their regulatory
      responses to specific emotional situations.

PMID- 20677868
TI  - Becoming a better person: temporal remoteness biases autobiographical memories
      for moral events.
AB  - Our autobiographical self depends on the differential recollection of our
      personal past, notably including memories of morally laden events. Whereas both
      emotion and temporal recency are well known to influence memory, very little is
      known about how we remember moral events, and in particular about the
      distribution in time of memories for events that were blameworthy or
      praiseworthy. To investigate this issue in detail, we collected a novel database
      of 758 confidential, autobiographical narratives for personal moral events from
      100 well-characterized healthy adults. Negatively valenced moral memories were
      significantly more remote than positively valenced memories, both as measured by
      the valence of the cue word that evoked the memory as well as by the content of
      the memory itself. The effect was independent of chronological age, ethnicity,
      gender or personality, arguing for a general emotional bias in how we construct
      our moral autobiography.

PMID- 20677869
TI  - Validity of young children's self-reports of their emotion in response to
      structured laboratory tasks.
AB  - Can young children report coherently on their emotions, and how do their reports
      contribute to our understanding of emotional development? Two-hundred six
      children ages 3 to 6 years participated in structured laboratory tasks designed
      to elicit a range of positive and negative emotions and indicated their emotional
      state following each task. Children's reports of their emotions meaningfully
      varied along with the nature of the different tasks during which they were
      collected (i.e., reports of negative and positive emotions differed across tasks
      designed to elicit those states). There were no sex differences on reports of any
      emotion and only small age differences. Multilevel modeling analyses demonstrated
      that children's self-reports of each emotion converged significantly with
      objective coding of expressions of those emotions across laboratory tasks; higher
      convergence for some emotions was associated with older age, higher verbal
      intelligence, and greater emotion-recognition abilities.

PMID- 20677870
TI  - Neuroticism's importance in understanding the daily life correlates of heart rate
      variability.
AB  - Individual differences in high-frequency heart rate variability (HRV) have been
      conceptualized in terms of a greater capacity to self-regulate problematic
      outcomes, but have also been conceptualized in terms of greater moment-to-moment
      flexibility. From a self-regulation perspective, higher HRV should be inversely
      correlated with trait neuroticism and problematic daily outcomes. From a
      flexibility perspective, high HRV should result in more state-like functioning-
      that is, functioning that is more contextual and less trait-like in nature. In
      the latter case, HRV and trait neuroticism may interact to predict problematic
      outcomes such that neuroticism should be a less consequential predictor at higher
      levels of HRV. The flexibility perspective was systematically supported in a
      daily experience-sampling protocol. Implications focus on theories of neuroticism
      and HRV.

PMID- 20677871
TI  - Reading chimpanzee faces: evidence for the role of verbal labels in categorical
      perception of emotion.
AB  - Categorical perception (CP) occurs when continuously varying stimuli are
      perceived as belonging to discrete categories. Thereby, perceivers are more
      accurate at discriminating between stimuli of different categories than between
      stimuli within the same category (Harnad, 1987; Goldstone, 1994). The current
      experiments investigated whether the structural information in the face is
      sufficient for CP to occur. Alternatively, a perceiver's conceptual knowledge, by
      virtue of expertise or verbal labeling, might contribute. In two experiments,
      people who differed in their conceptual knowledge (in the form of expertise,
      Experiment 1; or verbal label learning, Experiment 2) categorized chimpanzee
      facial expressions. Expertise alone did not facilitate CP. Only when perceivers
      first explicitly learned facial expression categories with a label were they more
      likely to show CP. Overall, the results suggest that the structural information
      in the face alone is often insufficient for CP; CP is facilitated by verbal
      labeling.

PMID- 20677872
TI  - Age-related changes in the integration of gaze direction and facial expressions
      of emotion.
AB  - Gaze direction influences younger adults' perception of emotional expressions,
      with direct gaze enhancing the perception of anger and joy, while averted gaze
      enhances the perception of fear. Age-related declines in emotion recognition and
      eye-gaze processing have been reported, indicating that there may be age-related
      changes in the ability to integrate these facial cues. As there is evidence of a
      positivity bias with age, age-related difficulties integrating these cues may be
      greatest for negative emotions. The present research investigated age differences
      in the extent to which gaze direction influenced explicit perception (e.g.,
      anger, fear and joy; Study 1) and social judgments (e.g., of approachability;
      Study 2) of emotion faces. Gaze direction did not influence the perception of
      fear in either age group. In both studies, age differences were found in the
      extent to which gaze direction influenced judgments of angry and joyful faces,
      with older adults showing less integration of gaze and emotion cues than younger
      adults. Age differences were greatest when interpreting angry expressions.
      Implications of these findings for older adults' social functioning are
      discussed.

PMID- 20677873
TI  - Emotion regulation and vulnerability to depression: spontaneous versus instructed
      use of emotion suppression and reappraisal.
AB  - Emotion dysregulation has long been thought to be a vulnerability factor for mood
      disorders. However, there have been few empirical tests of this idea. In this
      study, we tested the hypothesis that depression vulnerability is related to
      difficulties with emotion regulation by comparing recovered-depressed and never
      depressed participants (N = 73). In the first phase, participants completed
      questionnaires assessing their typical use of emotion regulation strategies. In
      the second phase, sad mood was induced using a film clip, and the degree to which
      participants reported to have spontaneously used suppression versus reappraisal
      to regulate their emotions was assessed. In the third phase, participants
      received either suppression or reappraisal instructions prior to watching a
      second sadness-inducing film. As predicted, suppression was found to be
      ineffective for down-regulating negative emotions, and recovered-depressed
      participants reported to have spontaneously used this strategy during the first
      sadness-inducing film more often than controls. However, the groups did not
      differ regarding the effects of induced suppression versus reappraisal on
      negative mood. These results provide evidence for a role for spontaneous but not
      instructed emotion regulation in depression vulnerability.

PMID- 20677874
TI  - Invisible expressions evoke core impressions.
AB  - Participants viewed "hybrid" faces that showed a facial expression (anger, fear,
      happiness, or sadness) only in the lowest spatial frequency (1-6 cycles/image),
      which was blended with the same face's neutral expression in the rest of the
      bandwidth (7-128 cycles/image). Participants rated the portrayed persons
      (compared to neutral images) as "friendly" when the lowest spatial frequencies
      showed a positive expression and "unfriendly" when the lowest spatial frequencies
      showed negative expressions. In contrast, the same hybrid images were explicitly
      judged as neutral and their "hidden" emotional expressions could not be
      explicitly recognized, as also confirmed by d' sensitivity measures. Finally, one
      patient (SS) who had the left anterior temporal lobe surgically resected
      (including the amygdala), failed to show the above described unconscious effects
      on friendliness judgments when viewing "afraid" and "sad" hybrid faces. We
      conclude that the lowest spatial frequencies of facial expressions can evoke
      "core" emotions without knowledge or awareness of a specific emotion but these
      core emotions can convey a clear "impression" of a person's character.

PMID- 20677876
TI  - The prepared emotional reflex: intentional preparation of automatic approach and
      avoidance tendencies as a means to regulate emotional responding.
AB  - Advance preparation of action courses toward emotional stimuli is an effective
      means to regulate impulsive emotional behavior. Our experiment shows that
      performing intentional acts of approach and avoidance in an evaluation task
      influences the unintended activation of approach and avoidance tendencies in
      another task in which stimulus valence is irrelevant. For the evaluation-relevant
      blocks, participants received either congruent (positive-approach, negative
      avoidance) or incongruent (positive-avoidance, negative-approach) mapping
      instructions. In the evaluation-irrelevant blocks, approach- and avoidance
      related lever movements were selected in response to a stimulus feature other
      than valence (affective Simon task). Response mapping in the evaluation task
      influenced performance in the evaluation-irrelevant task: An enhanced affective
      Simon effect was observed with congruent mapping instructions; in contrast, the
      effect was reversed when the evaluation task required incongruent responses.
      Thus, action instructions toward affective stimuli received in one task
      determined affective response tendencies in another task where these instructions
      were not in effect. These findings suggest that intentionally prepared short-term
      links between affective valence and motor responses elicit associated responses
      without a deliberate act of will, operating like a "prepared reflex."

PMID- 20677875
TI  - Cognitive reappraisal of negative affect: converging evidence from EMG and self
      report.
AB  - Prior psychophysiological studies of cognitive reappraisal have generally focused
      on the down-regulation of negative affect, and have demonstrated either changes
      in self-reports of affective experience, or changes in facial electromyography,
      but not both. Unfortunately, when taken separately, these measures are vulnerable
      to different sources of bias, and alternative explanations might account for
      changes in these indicators of negative affect. What is needed is a study that
      (a) obtains measures of self-reported affect together with facial
      electromyography, and (b) examines the use of reappraisal to regulate externally
      and internally generated affective responses. In the present study, participants
      up- or down-regulated negative affect in the context of both negative and neutral
      pictures. Up-regulation led to greater self reports of negative affect, as well
      as greater corrugator and startle responses to both negative and neutral stimuli.
      Down-regulation led to lesser reports of negative affect, and lesser corrugator
      responses to negative and neutral stimuli. These results extend prior research by
      (a) showing simultaneous effects on multiple measures of affect, and (b)
      demonstrating that cognitive reappraisal may be used both to regulate responses
      to negative stimuli and to manufacture a negative response to neutral stimuli.

PMID- 20677877
TI  - The effect of low versus high approach-motivated positive affect on memory for
      peripherally versus centrally presented information.
AB  - Emotions influence attention and processes involved in memory. Although some
      research has suggested that positive affect categorically influences these
      processes differently than neutral affect, recent research suggests that
      motivational intensity of positive affective states influences these processes.
      The present experiments examined memory for centrally or peripherally presented
      information after the evocation of approach-motivated positive affect. Experiment
      1 found that, relative to neutral conditions, pregoal, approach-motivated
      positive affect (caused by a monetary incentives task) enhanced memory for
      centrally presented information, whereas postgoal, low approach-motivated
      positive affect enhanced memory for peripherally presented information.
      Experiment 2 found that, relative to a neutral condition, high approach-motivated
      positive affect (caused by appetitive pictures) enhanced memory for centrally
      presented information but hindered memory for peripheral information. These
      results suggest a more complex relationship between positive affect and memory
      processes and highlight the importance of considering the motivational intensity
      of positive affects in cognitive processes.

PMID- 20677878
TI  - Age trends for failures of sustained attention.
AB  - Recent research has revealed an age-related reduction in errors in a sustained
      attention task, suggesting that sustained attention abilities improve with age.
      Such results seem paradoxical in light of the well-documented age-related
      declines in cognitive performance. In the present study, performance on the
      sustained attention to response task (SART) was assessed in a supplemented
      archival sample of 638 individuals between 14 and 77 years old. SART errors and
      response speed appeared to decline in a linear fashion as a function of age
      throughout the age span studied. In contrast, other measures of sustained
      attention (reaction time coefficient of variation), anticipation, and omissions)
      showed a decrease early in life and then remained unchanged for the rest of the
      life span. Thus, sustained attention shows improvements with maturation in early
      adulthood but then does not change with aging in older adults. On the other hand,
      aging across the entire life span leads to a more strategic (i.e., slower)
      response style that reduces the overt and critical consequences (i.e., SART
      errors) of momentary task disengagement.

PMID- 20677879
TI  - The face of aging: sensitivity to facial feature relations changes with age.
AB  - Fundamental to face processing is the ability to encode information about the
      spatial relations among facial features (configural information). Using a
      bizarreness rating paradigm, we found older adults differed from young adults in
      rating configurally distorted faces (eyes, mouth inverted) as less bizarre across
      all tested orientations (0 degrees  to 180 degrees ), and were more vulnerable to
      orientation effects when faces were rotated beyond 90 degrees . No age-related
      differences in perception of either unaltered faces or featurally distorted faces
      (eyes whitened, teeth blackened) occurred. These findings identify changes in
      sensitivity to configural information as an important factor in age-related
      differences in face perception.

PMID- 20677880
TI  - Age-related deficits in auditory confrontation naming.
AB  - The naming of manipulable objects in older and younger adults was evaluated
      across auditory, visual, and multisensory conditions. Older adults were less
      accurate and slower in naming across conditions, and all subjects were more
      impaired and slower to name action sounds than pictures or audiovisual
      combinations. Moreover, there was a sensory by age group interaction, revealing
      lower accuracy and increased latencies in auditory naming for older adults
      unrelated to hearing insensitivity but modest improvement to multisensory cues.
      These findings support age-related deficits in object action naming and suggest
      that auditory confrontation naming may be more sensitive than visual naming.

PMID- 20677881
TI  - Dementia: continuum or distinct entity?
AB  - The latent structure of dementia was examined in a group of 10,775 older adults
      with indicators derived from a neuropsychological test battery. The author
      conducted taxometric analysis of these data using mean above minus below a cut,
      maximum covariance, and latent mode factor analysis and found results more
      consistent with dementia as a dimensional (lying along a continuum) than
      categorical (representing a distinct entity) construct. A second study conducted
      with a group of 2,375 adults whose ages ranged from 21 to 64 years produced
      similar results. These findings denote that dementia, as measured by deficits in
      episodic memory, attention and concentration, executive function, and language,
      differs quantitatively rather than qualitatively from the cognitive status of
      adults without dementia. The implications of these results for classification,
      assessment, etiology, and prevention are discussed.

PMID- 20677882
TI  - Heterogeneity of cognitive trajectories in diverse older persons.
AB  - This study examined trajectories of cognitive change in psychometrically matched
      measures of episodic memory, semantic memory, and executive function in an
      ethnically, demographically, and cognitively diverse sample of older persons.
      Individual rates of change showed considerable heterogeneity in each domain.
      Baseline clinical diagnosis predicted differential change in semantic memory and
      executive function, dementia > mild cognitive impairment (MCI) > normal, but
      average decline in verbal episodic memory was similar across all 3 diagnostic
      groups. There was substantial overlap of distributions of cognitive change across
      baseline diagnostic groups for all 3 measures. Cognitive change was strongly
      related to change in clinical diagnosis. Rapid and similar change was present for
      all 3 cognitive measures in patients with dementia and in those with normal
      cognition and those with MCI who progressed clinically. In cognitively normal
      patients, verbal episodic memory change was greater than change in the other two
      domains. Global status, measured by the Clinical Dementia Rating scale (Morris,
      1993), predicted change in semantic memory and executive function, whereas APOE
      genotype predicted change in verbal episodic memory, and age had no effect on
      rates of change in any domain independent of global status and APOE. Results show
      important limitations in using cross-sectional diagnosis to predict prognosis and
      suggest that research to identify robust predictors of cognitive change across
      the full spectrum from normal to dementia is needed for better early
      identification of diseases that cause progressive decline.

PMID- 20677883
TI  - A corpus analysis of patterns of age-related change in conversational speech.
AB  - Conversational speech from over 300 speakers from 17 to 68 years of age was
      analyzed for age-related changes in the timing and content of spoken language
      production. Overall, several relationships between the lexical content, timing,
      and fluency of speech emerged, such that more novel and lower frequency words
      were associated with slower speech and higher levels of disfluencies. Speaker age
      was associated with slower speech and more filled pauses, particularly those
      associated with lexical selection. Increasing age, however, was also associated
      with longer utterances and greater lexical diversity. On balance, these analyses
      present a picture of age-related changes in speech performance that largely
      support data obtained from controlled laboratory studies. However, particular
      patterns of age-related change may be moderated in conversational situations.

PMID- 20677884
TI  - The association between computer use and cognition across adulthood: use it so
      you won't lose it?
AB  - Understanding the association between computer use and adult cognition has been
      limited until now by self-selected samples with restricted ranges of age and
      education. Here we studied effects of computer use in a large national sample (N
      = 2,671) of adults aged 32-84, assessing cognition with the Brief Test of Adult
      Cognition by Telephone (Tun & Lachman, 2005) and executive function with the Stop
      and Go Switch Task (Tun & Lachman, 2008). Frequency of computer activity was
      associated with cognitive performance after controlling for age, sex, education,
      and health status: That is, individuals who used the computer frequently scored
      significantly higher than those who seldom used the computer. Greater computer
      use was also associated with better executive function on a task-switching test,
      even after controlling for basic cognitive ability as well as demographic
      variables. These findings suggest that frequent computer activity is associated
      with good cognitive function, particularly executive control, across adulthood
      into old age, especially for those with lower intellectual ability.

PMID- 20677885
TI  - The effects of aging in delay and trace human eyeblink conditioning.
AB  - Normal aging has been shown to impact performance during human eyeblink classical
      conditioning, with older adults showing lower conditioning levels than younger
      adults. Previous findings showed younger adults can acquire both delay and trace
      conditioning concurrently, but it is not known whether older adults can learn
      under the same conditions. Present results indicated older adults did not produce
      a significantly greater number of conditioned responses during acquisition, but
      their ability to time eyeblink responses prior to the unconditioned stimulus was
      preserved. The decline in eyeblink conditioning that typically accompanies aging
      has been extended to concurrent presentations of delay and trace conditioning
      trials.

PMID- 20677886
TI  - Getting the message across: age differences in the positive and negative framing
      of health care messages.
AB  - Although valenced health care messages influence impressions, memory, and
      behavior (Levin, Schneider, & Gaeth, 1998) and the processing of valenced
      information changes with age (Carstensen & Mikels, 2005), these 2 lines of
      research have thus far been disconnected. This study examined impressions of, and
      memory for, positively and negatively framed health care messages that were
      presented in pamphlets to 25 older adults and 24 younger adults. Older adults
      relative to younger adults rated positive pamphlets more informative than
      negative pamphlets and remembered a higher proportion of positive to negative
      messages. However, older adults misremembered negative messages to be positive.
      These findings demonstrate the age-related positivity effect in health care
      messages with promise as to the persuasive nature and lingering effects of
      positive messages.

PMID- 20677887
TI  - Where people live and die makes a difference: Individual and geographic
      disparities in well-being progression at the end of life.
AB  - Life-span psychological research has long been interested in the contextual
      embeddedness of individual development. To examine whether and how regional
      variables relate to between-person disparities in the progression of late-life
      well-being, we applied three-level growth curve models to 24-year longitudinal
      data from deceased participants of the German Socio-Economic Panel Study (N =
      3,427; age at death = 18 to 101 years). Results indicated steep declines in well
      being with impending death, with some 8% of the between-person differences in
      both level and decline of well-being reflecting between-county differences.
      Exploratory analyses revealed that individuals living and dying in less affluent
      counties reported lower late-life well-being, controlling for key individual
      predictors, including age at death, gender, education, and household income. The
      regional variables examined did not directly relate to well-being change but were
      found to moderate (e.g., amplify) the disparities in change attributed to
      individual variables. Our results suggest that resource-poor counties provide
      relatively less fertile grounds for successful aging until the end of life and
      may serve to exacerbate disparities. We conclude that examinations of how
      individual and residential characteristics interact can further our understanding
      of individual psychological outcomes and suggest routes for future inquiry.

PMID- 20677888
TI  - The structure and health correlates of trait repetitive thought in older adults.
AB  - Repetitive thought (RT) involves frequent or prolonged thoughts about oneself and
      one's world, encompassing discrete forms such as trait worry, rumination,
      processing, and reminiscing. These forms of RT can be described using 3 basic,
      underlying qualities: total propensity for RT of all types, valence (positive vs.
      negative content), and purpose (searching or uncertainty vs. solving or
      certainty). The adaptiveness of discrete forms with regard to health is likely to
      be related to these qualities, particularly valence and total propensity. The
      present study confirmed the model and identified the relationship of these
      qualities of RT to subjective psychological, physical, and cognitive health in
      older adults aged 60-94 (N = 179). As predicted, more negatively valenced trait
      RT was associated with worse psychological, physical, and cognitive health. More
      total propensity for RT was associated only with worse psychological health.
      Searching purpose was associated only with worse cognitive health. In turn,
      negatively valenced RT was predicted by poorer executive functions, suggesting
      that such functions may be important for directing this quality of RT. The
      valence of older adults' RT is important insofar as it may contribute to their
      sense of good or ill health. However, the propensity for all kinds of RT to
      associate with poorer psychological health may reflect the co-occurrence of
      negative and positive RT, such as rumination and emotional processing. Although
      RT has not been extensively investigated in older adults, it appears to play an
      important role in their subjective health.

PMID- 20677889
TI  - Individual differences in perceiving and recognizing faces-One element of social
      cognition.
AB  - Recognizing faces swiftly and accurately is of paramount importance to humans as
      a social species. Individual differences in the ability to perform these tasks
      may therefore reflect important aspects of social or emotional intelligence.
      Although functional models of face cognition based on group and single case
      studies postulate multiple component processes, little is known about the ability
      structure underlying individual differences in face cognition. In 2 large
      individual differences experiments (N = 151 and N = 209), a broad variety of face
      cognition tasks were tested and the component abilities of face cognition-face
      perception, face memory, and the speed of face cognition-were identified and then
      replicated. Experiment 2 also showed that the 3 face-cognition abilities are
      clearly distinct from immediate and delayed memory, mental speed, general
      cognitive ability, and object cognition. These results converge with functional
      and neuroanatomical models of face cognition by demonstrating the difference
      between face perception and face memory. The results also underline the
      importance of distinguishing between speed and accuracy of face cognition.
      Together our results provide a first step toward establishing face-processing
      abilities as an independent ability reflecting elements of social intelligence.

PMID- 20677891
TI  - Smearing the opposition: implicit and explicit stigmatization of the 2008 U.S.
      Presidential candidates and the current U.S. President.
AB  - Four studies investigated whether political allegiance and salience of outgroup
      membership contribute to the phenomenon of acceptance of false, stigmatizing
      information (smears) about political candidates. Studies 1-3 were conducted in
      the month prior to the 2008 U.S. Presidential election and together demonstrated
      that pre-standing opposition to John McCain or Barack Obama, as well as the
      situational salience of differentiating social categories (i.e., for Obama, race;
      for McCain, age), contributed to the implicit activation and explicit endorsement
      of smearing labels (i.e., Obama is Muslim; McCain is senile). The influence of
      salient differentiating categories on smear acceptance was particularly
      pronounced among politically undecided individuals. Study 4 clarified that social
      category differences heighten smear acceptance, even if the salient category is
      semantically unrelated to the smearing label, showing that, approximately 1 year
      after the election, the salience of race amplified belief that Obama is a
      socialist among undecided people and McCain supporters. Taken together, these
      findings suggest that, at both implicit and explicit cognitive levels, social
      category differences and political allegiance contribute to acceptance of smears
      against political candidates.

PMID- 20677890
TI  - Exploring the link between racial discrimination and substance use: what
      mediates? What buffers?
AB  - The relation between perceived racial discrimination and substance use was
      examined in 2 studies that were based on the prototype-willingness model
      (Gibbons, Gerrard, & Lane, 2003). Study 1, using structural equation modeling,
      revealed prospective relations between discrimination and use 5 years later in a
      panel of African American adolescents (M age 10.5 years at Time 1 [T1]) and their
      parents. For both groups, the relation was mediated by anger and/or hostility.
      For the adolescents, it was also mediated by behavioral willingness, and it was
      moderated by supportive parenting. Study 2 was a lab experiment in which a subset
      of the Study 1 adolescents (M age = 18.5 years) was asked to imagine a
      discriminatory experience, and then their affect and drug willingness were
      assessed. As in the survey study, discrimination was associated with more drug
      willingness, and that relation was again mediated by anger and moderated by
      supportive parenting. Implications of the results for research and interventions
      involving reactions to racial discrimination are discussed.

PMID- 20677892
TI  - Red, rank, and romance in women viewing men.
AB  - In many nonhuman species of vertebrates, females are attracted to red on male
      conspecifics. Red is also a signal of male status in many nonhuman vertebrate
      species, and females show a mating preference for high-status males. These red
      attraction and red-status links have been found even when red is displayed on
      males artificially. In the present research, we document parallels between human
      and nonhuman females' response to male red. Specifically, in a series of 7
      experiments we demonstrate that women perceive men to be more attractive and
      sexually desirable when seen on a red background and in red clothing, and we
      additionally show that status perceptions are responsible for this red effect.
      The influence of red appears to be specific to women's romantic attraction to
      men: Red did not influence men's perceptions of other men, nor did it influence
      women's perceptions of men's overall likability, agreeableness, or extraversion.
      Participants showed no awareness that the research focused on the influence of
      color. These findings indicate that color not only has aesthetic value but can
      carry meaning and impact psychological functioning in subtle, important, and
      provocative ways.

PMID- 20677894
TI  - Interaction-dominant dynamics in human cognition: beyond 1/f(alpha) fluctuation.
AB  - It has been suggested that human behavior in general and cognitive performance in
      particular emerge from coordination between multiple temporal scales. In this
      article, we provide quantitative support for such a theory of interaction
      dominant dynamics in human cognition by using wavelet-based multifractal analysis
      and accompanying multiplicative cascading process on the response series of 4
      different cognitive tasks: simple response, word naming, choice decision, and
      interval estimation. Results indicated that the major portion of these response
      series had multiplicative interactions between temporal scales, visible as
      intermittent periods of large and irregular fluctuations (i.e., a multifractal
      structure). Comparing 2 component-dominant models of 1/f(alpha) fluctuations in
      cognitive performance with the multiplicative cascading process indicated that
      the multifractal structure could not be replicated by these component-dominant
      models. Furthermore, a similar multifractal structure was shown to be present in
      a model of self-organized criticality in the human nervous system, similar to a
      spatial extension of the multiplicative cascading process. These results
      illustrate that a wavelet-based multifractal analysis and the multiplicative
      cascading process form an appropriate framework to characterize interaction
      dominant dynamics in human cognition. This new framework goes beyond the
      identification of 1/f(alpha) power laws and non-gaussian distributions in
      response series as used in previous studies. The present article provides
      quantitative support for a paradigm shift toward interaction-dominant dynamics in
      human cognition.

PMID- 20677893
TI  - Phonological universals constrain the processing of nonspeech stimuli.
AB  - Domain-specific systems are hypothetically specialized with respect to the
      outputs they compute and the inputs they allow (Fodor, 1983). Here, we examine
      whether these 2 conditions for specialization are dissociable. An initial
      experiment suggests that English speakers could extend a putatively universal
      phonological restriction to inputs identified as nonspeech. A subsequent
      comparison of English and Russian participants indicates that the processing of
      nonspeech inputs is modulated by linguistic experience. Striking, qualitative
      differences between English and Russian participants suggest that they rely on
      linguistic principles, both universal and language-particular, rather than
      generic auditory processing strategies. Thus, the computation of idiosyncratic
      linguistic outputs is apparently not restricted to speech inputs. This conclusion
      presents various challenges to both domain-specific and domain-general accounts
      of cognition.

PMID- 20677895
TI  - Attentional sensitization of unconscious cognition: task sets modulate subsequent
      masked semantic priming.
AB  - According to classical theories, automatic processes are autonomous and
      independent of higher level cognitive influence. In contrast, the authors propose
      that automatic processing depends on attentional sensitization of task-congruent
      processing pathways. In 3 experiments, the authors tested this hypothesis with a
      modified masked semantic priming paradigm during a lexical decision task by
      measuring event-related potentials (ERPs): Before masked prime presentation,
      participants attended an induction task either to semantic or perceptual stimulus
      features designed to activate a semantic or perceptual task set, respectively.
      Semantic priming effects on the N400 ERP component, an electrophysiological index
      of semantic processing, were obtained when a semantic task set was induced
      immediately before subliminal prime presentation, whereas a previously induced
      perceptual task set attenuated N400 priming. Across experiments, comparable
      results were obtained regardless of the difficulty level and the verbal or
      nonverbal nature of the induction tasks. In line with the proposed attentional
      sensitization model, unconscious semantic processing is enhanced by a semantic
      and attenuated by a perceptual task set. Hence, automatic processing of
      unconscious stimuli is susceptible to top-down control for optimizing goal
      related information processing.

PMID- 20677896
TI  - From sunshine to double arrows: an evaluation window account of negative
      compatibility effects.
AB  - In category priming, target stimuli are to be sorted into 2 categories. Prime
      stimuli preceding targets typically facilitate processing of targets when primes
      and targets are members of the same category, relative to the case in which both
      stem from different categories, a positive compatibility effect (PCE). But
      negative compatibility effects (NCEs) are also sometimes observed. An evaluation
      window account (Klauer, Teige-Mocigemba, & Spruyt, 2009) of PCE and NCE in
      evaluative priming (category good versus category bad) is applied to masked arrow
      priming (Eimer & Schlaghecken, 1998; category left versus category right). Key
      principles of the account are that participants evaluate incoming evidence across
      a time window, and decisions about stimulus category are driven by changes in
      evidence weighted according to the Weber-Fechner law, leading to NCE for primes
      falling outside the time window and PCE for primes inside the time window. In
      Experiments 1-4, factors considered obligatory for NCE by current accounts of
      arrow priming are successively removed; yet, NCE remained intact as predicted by
      the evaluation window account. Furthermore, the evaluation window account, but
      none of the current accounts, predicts NCE without a stimulus intervening between
      prime and target at intermediate prime-target stimulus-onset asynchrony
      (Experiment 5) and when target onset comes as a surprise (Experiment 6). We
      conclude that the evaluation window account describes a hitherto overlooked
      mechanism that contributes to PCE and NCE in arrow priming and that it appears to
      generalize beyond the confines of evaluative priming to the diverse class of
      category-priming paradigms.

PMID- 20677897
TI  - Feelings don't come easy: studies on the effortful nature of feelings.
AB  - We propose that experience of emotion is a mental phenomenon, which requires
      resources. This hypothesis implies that a concurrent cognitive load diminishes
      the intensity of feeling since the 2 activities are competing for the same
      resources. Two sets of experiments tested this hypothesis. The first line of
      experiments (Experiments 1-4) examined the intensity of participants' feelings as
      they performed a secondary (backward counting) task. The results showed that the
      intensity of both negative and positive feelings diminished under a cognitive
      load and that this attenuation of feeling was not mediated by either distraction
      from external stimuli or demand characteristics. In the second set of experiments
      (Experiments 5-6), load was created by asking the participants to focus on the
      feelings. Even in these circumstances, the participants who were under load
      reported a lower intensity of feeling than those who were not under load. We
      explain these findings in terms of a resource-dependent model of emotional
      experience. Possible implications of our findings for a broader class of
      phenomenological experiences are succinctly discussed.

PMID- 20677898
TI  - Naive theories of intelligence and the role of processing fluency in perceived
      comprehension.
AB  - Previous research overwhelmingly suggests that feelings of ease people experience
      while processing information lead them to infer that their comprehension is high,
      whereas feelings of difficulty lead them to infer that their comprehension is
      low. However, the inferences people draw from their experiences of processing
      fluency should also vary in accordance with their naive theories about why new
      information might be easy or difficult to process. Five experiments that involved
      reading novel texts showed that participants who view intelligence as a fixed
      attribute, and who tend to interpret experiences of processing difficulty as an
      indication that they are reaching the limits of their ability, reported lower
      levels of comprehension as fluency decreased. In contrast, participants who view
      intelligence as a malleable attribute that develops through effort, and who do
      not tend to interpret experiences of processing difficulty as pertaining to some
      innate ability, did not report lower levels of comprehension as fluency
      decreased. In fact, when these participants were particularly likely to view
      effort as leading to increased mastery, decreases in fluency led them to report
      higher levels of comprehension.

PMID- 20677900
TI  - Advances in novel drug delivery strategies for breast cancer therapy.
AB  - Breast cancer remains one of the world's most devastating diseases. However,
      better understanding of tumor biology and improved diagnostic devices could lead
      to improved therapeutic outcomes. Nanotechnology has the potential to
      revolutionize cancer diagnosis and therapy. Various nanocarriers have been
      introduced to improve the therapeutic efficacy of anticancer drugs, including
      liposomes, polymeric micelles, quantum dots, nanoparticles, and dendrimers.
      Recently, targeted drug delivery systems for anti-tumor drugs have demonstrated
      great potential to lower cytotoxicity and increase therapeutic effects. Various
      ligands/approaches have been explored for targeting breast cancer. This paper
      provides an overview of breast cancer, conventional therapy, potential of
      nanotechnology in management of breast cancer, and rational approaches for
      targeting breast cancer.

PMID- 20677899
TI  - Conceptual distinctiveness supports detailed visual long-term memory for real
      world objects.
AB  - Humans have a massive capacity to store detailed information in visual long-term
      memory. The present studies explored the fidelity of these visual long-term
      memory representations and examined how conceptual and perceptual features of
      object categories support this capacity. Observers viewed 2,800 object images
      with a different number of exemplars presented from each category. At test,
      observers indicated which of 2 exemplars they had previously studied. Memory
      performance was high and remained quite high (82% accuracy) with 16 exemplars
      from a category in memory, demonstrating a large memory capacity for object
      exemplars. However, memory performance decreased as more exemplars were held in
      memory, implying systematic categorical interference. Object categories with
      conceptually distinctive exemplars showed less interference in memory as the
      number of exemplars increased. Interference in memory was not predicted by the
      perceptual distinctiveness of exemplars from an object category, though these
      perceptual measures predicted visual search rates for an object target among
      exemplars. These data provide evidence that observers' capacity to remember
      visual information in long-term memory depends more on conceptual structure than
      perceptual distinctiveness.

PMID- 20677901
TI  - The experimental research of nerve fibers compensation amplification innervation
      of ulnar nerve and musculocutaneous nerve in rhesus monkeys.
AB  - This experiment intended to authenticate the compensation and amplification
      effect of regenerated nerve fibers after nerve injury in primate. The Rhesus
      Monkeys right ulnar nerves and musculocutaneous nerves were chosed. The proximal
      impaired ulnar nerve as the proximal end and the distal impaired ulnar nerve
      musculocutaneous nerve as the distal ends. The ulnar nerve proximal stump fibers
      can grow into both the ulnar nerve distal stump and the musculocutaneus nerve at
      the same time and established two different electrophysiological conduction
      passageway. There exist nerve fibers compensation amplification effect after
      peripheral nerve injury on Rhesus Monkeys.

PMID- 20677902
TI  - Biosynthesis of cephalosporin-C acylase enzyme: optimal media design,
      purification, and characterization.
AB  - 7-aminocephalosporanic acid (7-ACA) is the key intermediate for the synthesis of
      semisynthetic cephalosporin antibiotics and enzyme cephalosporin-C acylase (CPC
      acylase) plays an important role in the conversion of cephalosporin-C to 7-ACA.
      With an aim to increase the yield of 7-ACA production by Micrococcus luteus, a
      stepwise strategy, statistical medium was applied for optimizing the medium
      composition for the production of CPC acylase. Purified enzyme was found to be of
      80 kDa. The optimum pH and temperature for the production of 7-ACA were 7.6 and
      340C, respectively. The Km and Vmax were estimated to be 9.43 mg/mL and 7.65
      U/mL, respectively.

PMID- 20677903
TI  - Potential c-myc antisense oligonucleotide carriers: PCl/PEG/PEI and PLL/PEG/PEI.
AB  - In this work, positively charged, micelle-forming polymers were synthesized and
      used as a model vector to deliver antisense oligodeoxynucleotide (ASODN) into
      melanoma cells. Polymers and polymer/ASODN complexes were characterized by DLS
      according to size, charge, and critical micelle concentration. Nanosize and
      spherical complexes were observed by AFM. Complexes did not reveal significant
      toxicity to melanoma cells. Antiproliferative effect of the complexes was
      observed by immunocytochemical staining and estimated as 56.8% with N/P:9. High
      amount of apoptosis and very small amount of necrosis were estimated. According
      to the results, these positively charged polymers forming micelle-like structures
      seem promising as ASODN carriers.

PMID- 20677904
TI  - The late effects of radiation on lifespan, lymphocyte proliferation and p53
      haplodeficiency in mice.
AB  - PURPOSE: We investigated the effect of irradiation on the lifespan of eight-week
      old mice, the number of lymphocytes in bone marrow and the levels of p53 protein
      expression in the splenocytes. METHODS AND MATERIALS: Eight-week-old mice, wild
      type p53 (p53(+/+)) and heterozygous p53 (p53(+/-)), were irradiated with 3 Gy.
      The cell numbers and cell cycle phases of bone marrow cells were determined by
      flow cytometry. The splenocyte proliferation was evaluated by a fluorescent cell
      viability assay. The p53 expression was evaluated by Western blotting. RESULTS:
      The lifespan of the irradiated mice was shorter than that of the non-irradiated
      mice. In irradiated 72-week-old p53(+/+) mice and 56-week-old p53(+/-) mice, the
      number of lymphocytes in bone marrow decreased as compared to that in the non
      irradiated mice. In 56-week-old p53(+/-) mice, the S- and G2/M-phases of
      lymphocytes in the irradiated mice were increased compared to that in the non
      irradiated mice. The splenocyte proliferation in p53(+/+) mice decreased with
      age, and the proliferation in the irradiated mice was much lower than that in the
      non-irradiated mice. In 72-week-old p53(+/+) mice after re-irradiation, the p53
      protein expression in the splenocytes of the irradiated mice was delayed as
      compared to those from the non-irradiated mice. CONCLUSION: We suggest that the
      decrease in the number of lymphocytes in bone marrow and the delayed p53
      expression in splenocytes from the irradiated mice are related to the shortened
      lifespan after irradiation at a young age.

PMID- 20677905
TI  - Radiation-inducible PTEN expression radiosensitises hepatocellular carcinoma
      cells.
AB  - PURPOSE: To test the radiosensitising effects of a tumour-suppressor gene,
      phosphatase and tensin homologue deleted from chromosome 10 (PTEN), in
      hepatocellular carcinoma cells (HCC). MATERIALS AND METHODS: Radiation-induced
      wild-type PTEN or mutant PTEN was transfected into the SMMC-7721 human
      hepatocellular carcinoma cells. The expressions of PTEN and serine/threonine
      protein kinase (Akt) were detected by Western blot analysis. 3-(4,5)
      dimethylthiahiazo-(-z-y1)-3,5-di-phenytetrazoliumromide (MTT) absorbance and
      clonogenic survival assays were used to determine cell viability, proliferation
      and radiosensitivity. By performing cell-cycle analysis, terminal
      deoxynucleotidyltransferase (TdT)-mediated dUTP biotin nick end labelling (TUNEL)
      assays and gamma-histone H2A (gamma-H2AX) formation assays, we were able to
      explore the mechanism of PTEN enhancement of radiosensitivity. RESULTS:
      Restoration of wild-type PTEN induced growth suppression and sensitised the cells
      to ionising radiation specifically by its lipid phosphatase activity through the
      PTEN-phosphatidylinositol 3-kinase (PI3K)-Akt signalling pathway. Restoring PTEN
      function correlated with G2/M arrest, apoptosis and the retardation of repair of
      radiation-induced double strand breaks (DSB). CONCLUSIONS: Our study suggests
      that strategies designed to restore the expression of PTEN may represent
      promising new therapies for sensitising HCC cells to ionising radiation.

PMID- 20677906
TI  - Manual aspiration prior to stenting does not reduce the incidence of filter no
      reflow in saphenous vein graft lesions protected by FilterWire EX/EZ.
AB  - BACKGROUND: The beneficial role of manual thrombus aspiration in thrombus
      containing lesions has been proven in acute myocardial infarction but data is
      lacking in saphenous vein graft lesions. METHODS: From January 2004 to December
      2008, 74 consecutive post-bypass patients underwent percutaneous coronary
      interventions to 76 saphenous vein graft lesions under the protection of
      FilterWire EX/EZ. Among them, the latest 25 consecutive patients with 25 lesions
      were treated with manual aspiration before stenting. The incidence of filter no
      reflow was compared between patients with and without manual aspiration
      pretreatment. RESULTS: No major difference in demography, clinical, lesion, and
      procedure characteristics, and in-hospital outcome has been observed between the
      two patient groups. Most importantly, the incidence of filter no reflow has not
      been reduced (32.0% versus 19.6%, P = 0.26) by manual aspiration, even among
      thrombus-containing lesions (63.2% versus 64.7%, P = 1.00). The absence of
      diabetes mellitus is found to be the independent predictor for the occurrence of
      filter no reflow. CONCLUSIONS: Adjunctive manual thrombus aspiration fails to
      reduce the filter no reflow, and probably has no additional benefit in saphenous
      vein graft lesions already protected by FilterWire EX/EZ.

PMID- 20677907
TI  - Bcl-2 improves myoblast sheet therapy in rat chronic heart failure.
AB  - Myoblast transplantation therapy for chronic heart failure (HF) is impaired by
      early donor cell death and reduced graft viability. Although epicardial
      implantation of cell sheets can prevent the initial loss of transplanted cells,
      limited vascularization subjects the sheets to apoptotic stress. We studied the
      efficacy of antiapoptotic bcl2 in myoblast sheet therapy for rat chronic HF.
      Myocardial infarction was induced by left anterior descending coronary artery
      ligation and HF was allowed to develop for 4 weeks. Thereafter, wild type (L6-WT;
      n=16) or Bcl-2-expressing (L6-Bcl2; n=19) myoblast sheets were transplanted
      epicardially. Control rats (n=21) underwent left anterior descending coronary
      artery ligation and re-thoracotomy. Five rats were sham-operated in both
      surgeries. Four weeks after transplantation, only the L6-Bcl2 rats showed
      improved left ventricular ejection fraction. Their vascular density in the
      damaged myocardium was greater, and they had more proliferating cells. The L6
      Bcl2 group had an increased amount of myocytes in the infarct area. Soluble
      factors from L6-Bcl2 sheets induced a 2.9-fold increase in endothelial cell
      proliferation, and enhanced endothelial wound healing as compared to the L6-WT
      sheets. These effects were inhibited by SU5416 and were thus dependent on
      Flt1/Flk1 signaling. In conclusion, bcl2 improves efficacy of myoblast sheet
      transplantation and promotes proangiogenic paracrine signaling.

PMID- 20677908
TI  - Inhibition of LXRalpha-dependent steatosis and oxidative injury by
      liquiritigenin, a licorice flavonoid, as mediated with Nrf2 activation.
AB  - Liver X receptor-alpha (LXRalpha) functions as a major regulator of lipid
      homeostasis through activation of sterol regulatory element binding protein-1c
      (SREBP-1c), which promotes hepatic steatosis and steatohepatitis. NF-E2-related
      factor 2 (Nrf2) is the crucial transcription factor that is necessary for the
      induction of antioxidant enzymes. This study investigated the potential of
      liquiritigenin (LQ), a hepatoprotective flavonoid in licorice, to inhibit
      LXRalpha-induced hepatic steatosis, and the underlying mechanism of the action.
      LQ treatment attenuated fat accumulation and lipogenic gene induction in the
      liver of mice fed a high fat diet. Also, LQ had the ability to inhibit oxidative
      liver injury, as shown by decreases in thiobarbituric acid reactive substances
      formation and nitrotyrosinylation. Moreover, LQ treatment antagonized LXRalpha
      agonist (T0901317)-mediated SREBP-1c activation, and transactivation of the
      lipogenic target genes. LQ was found to activate Nrf2, and the ability of LQ to
      inhibit LXRalpha-mediated SREBP-1c activation was reversed by Nrf2 deficiency,
      which supports the inhibitory role of Nrf2 in LXRalpha-dependent lipogenesis.
      Consistently, treatment with other Nrf2 activators or forced expression of Nrf2
      also inhibited LXRalpha-mediated SREBP-1c activation. Our results demonstrate
      that LQ has an efficacy to activate Nrf2, which contributes to inhibiting the
      activity of LXRalpha that leads to SREBP-1c induction and hepatic steatosis.

PMID- 20677909
TI  - Mechanistic insight into DNA damage and repair in ischemic stroke: exploiting the
      base excision repair pathway as a model of neuroprotection.
AB  - Stroke is a common cause of death and serious long-term adult disability.
      Oxidative DNA damage is a severe consequence of oxidative stress associated with
      ischemic stroke. The accumulation of DNA lesions, including oxidative base
      modifications and strand breaks, triggers cell death in neurons and other
      vulnerable cell populations in the ischemic brain. DNA repair systems,
      particularly base excision repair, are endogenous defense mechanisms that combat
      oxidative DNA damage. The capacity for DNA repair may affect the susceptibility
      of neurons to ischemic stress and influence the pathological outcome of stroke.
      This article reviews the accumulated understanding of molecular pathways by which
      oxidative DNA damage is triggered and repaired in ischemic cells, and the
      potential impact of these pathways on ischemic neuronal cell death/survival.
      Genetic or pharmacological strategies that target the signaling molecules in DNA
      repair responses are promising for potential clinically effective treatment.
      Further understanding of mechanisms for oxidative DNA damage and its repair
      processes may lead to new avenues for stroke management.

PMID- 20677911
TI  - Transgene loss and changes in the promoter methylation status as determinants for
      expression duration in nonviral gene transfer for factor IX.
AB  - Advances in delivery techniques and in expression construct design have renewed
      interest in nonviral gene transfer. Here, we test plasmid or bacterial backbone
      free minicircle vectors for factor IX (FIX) expression by hydrodynamic liver
      directed delivery. Both constructs are driven by a hepatic control region, the
      human alpha(1)-antitrypsin promoter, which results in long-term expression in FIX
      knockout mice. However, levels of expression were higher and expression loss over
      time was reduced when using minicircles. Even at the highest expression levels
      (>700% of normal) FIX was fully functional. Transgene loss was the main
      determinant for expression loss over time for both vector types. A significant
      effect of gene silencing was observed only for the plasmid, not for the
      minicircle vector. To determine the influence of promoter methylation, we
      performed bisulfite-mediated conversion and sequencing of vector DNA on days 14
      and 100 after gene transfer. We determined a higher frequency of methyl-protected
      cytosines in CpGs and a lower degree of demethylation at bacterial Dcm
      methylation sequences near transcription factor-binding sites in the alpha(1)
      antitrypsin promoter in plasmid compared with minicircle mice on day 100.
      Therefore, the methylation status might reflect differences in the levels and
      durability of expression. Judging from the high levels of functional FIX
      obtained, small fractions of liver or single liver segments should be sufficient
      to reach therapeutic efficacy in translating hydrodynamic delivery to humans.
      However, transgene loss remains to be addressed to further guarantee sustained
      expression over time.

PMID- 20677910
TI  - C-terminus of heat shock cognate 70 interacting protein increases following
      stroke and impairs survival against acute oxidative stress.
AB  - The decision to remove or refold oxidized, denatured, or misfolded proteins by
      heat shock protein 70 and its binding partners is critical to determine cell fate
      under pathophysiological conditions. Overexpression of the ubiquitin ligase C
      terminus of HSC70 interacting protein (CHIP) can compensate for failure of other
      ubiquitin ligases and enhance protein turnover and survival under chronic
      neurological stress. The ability of CHIP to alter cell fate after acute
      neurological injury has not been assessed. Using postmortem human tissue samples,
      we provide the first evidence that cortical CHIP expression is increased after
      ischemic stroke. Oxygen glucose deprivation in vitro led to rapid protein
      oxidation, antioxidant depletion, proteasome dysfunction, and a significant
      increase in CHIP expression. To determine if CHIP upregulation enhances neural
      survival, we overexpressed CHIP in vitro and evaluated cell fate 24 h after acute
      oxidative stress. Surprisingly, CHIP overexpressing cells fared worse against
      oxidative injury, accumulated more ubiquitinated and oxidized proteins, and
      experienced decreased proteasome activity. Conversely, using small interfering
      RNA to decrease CHIP expression in primary neuronal cultures improved survival
      after oxidative stress, suggesting that increases in CHIP observed after stroke
      like injuries are likely correlated with diminished survival and may negatively
      impact the neuroprotective potential of heat shock protein 70.

PMID- 20677912
TI  - Store-operated Ca(2+) entry is expressed in human endothelial progenitor cells.
AB  - Endothelial progenitor cells (EPCs) may be recruited from the bone marrow to
      sites of tissue regeneration to sustain neovascularization and
      reendothelialization after acute vascular injury. This feature makes them
      particularly suitable for cell-based therapy. In mature endothelium, store
      operated Ca(2+) entry (SOCE) is activated following emptying of inositol-1,4,5
      trisphosphate-sensitive stores, and controls a wide number of functions,
      including proliferation, nitric oxide synthesis, and vascular permeability. The
      present work aimed at investigating SOCE expression in EPCs harvested from both
      peripheral blood (PB-EPCs) and umbilical cord blood (UCB-EPCs) by employing both
      Ca(2+) imaging and molecular biology techniques. SOCE was induced upon either
      pharmacological (ie, cyclopiazonic acid) or physiological (ie, ATP) depletion of
      the intracellular Ca(2+) pool. Further, store-dependent Ca(2+) entry was
      inhibited by the SOCE inhibitor, N-(4-[3,5-bis(trifluoromethyl)-1H-pyrazol-1
      yl]phenyl)-4-methyl-1,2,3-thiadiazole-5-carboxamide (BTP-2). Real-time reverse
      transcription-polymerase chain reaction and western blot analyses showed that
      both PB-EPCs and UCB-EPCs express all the molecular candidates to mediate SOCE in
      differentiated cells, including TRPC1, TRPC4, Orai1, and Stim1. Moreover,
      pharmacological maneuvers demonstrated that, as well as in differentiated
      endothelial cells, the signal transduction pathway leading to depletion of the
      intracellular Ca(2+) pool impinged on the phospholipase C/inositol-1,4,5
      trisphosphate pathway. Finally, blockage of SOCE with BTP-2 impaired PB-EPC
      proliferation. These findings provide the first evidence that EPCs express SOCE,
      which might thus be regarded as a novel target to enhance the regenerative
      outcome of cell-based therapy.

PMID- 20677913
TI  - Development of a novel polyethylene glycol-corticosteroid-conjugate with an acid
      cleavable linker.
AB  - BACKGROUND: Corticosteroids like dexamethasone are often used in the treatment of
      inflammatory diseases. Despite efficacy, their use is limited by severe side
      effects. Targeted drug-delivery to the site of inflammation would be advantageous
      for the patients. Macromolecules can be used for this approach, because they
      accumulate at sites of inflammation due to the enhanced permeability and
      retention effect. PURPOSE: Our aim was to develop a polymer-corticosteroid
      conjugate for the treatment of inflammatory diseases. The authors covalently
      linked a derivative of dexamethasone to the macromolecule polyethylene glycol
      (PEG), using an acid-cleavable linker to achieve lysosomal drug-release. METHODS:
      The corticosteroid-PEG-conjugate was synthesized and characterized by nuclear
      magnetic resonance spectroscopy (NMR) and mass spectrometry. Cleavage experiments
      were performed to study the nature of products after incubation at acidic pH, and
      the efficacy of the conjugate was tested in two model cell lines. RESULTS: Acid
      hydrolysis of the novel corticosteroid-PEG-conjugate resulted in two new
      derivatives of dexamethasone. The conjugate was effective in both model cell
      lines showing lysosomal release and efficacy of the cleavage products. DISCUSSION
      AND CONCLUSION: The authors new corticosteroid-PEG-conjugate shows glucocorticoid
      activity and should be developed further to treat inflammatory diseases with
      reduced side-effects while retaining drug efficacy.

PMID- 20677914
TI  - The antiangiogenic efficacy of NGR-modified PEG-DSPE micelles containing
      paclitaxel (NGR-M-PTX) for the treatment of glioma in rats.
AB  - Aminopeptidase N (APN), recognized by Asn-Gly-Arg (NGR) peptides, is expressed in
      the pericytes associated with the BBB, and the main objective of this study is to
      confirm the hypothesis that NGR-modified DSPE-PEG micelles containing paclitaxel
      (NGR-M-PTX) can bind to and kill brain tumor angiogenic blood vessels and
      penetrate into the brain tumor interstitial space, resulting in direct cell
      death. NGR-M-PTX is prepared by a thin-film hydration method. The in vitro
      targeting characteristics of NGR-modified micelles on BMEC (murine brain
      microvascular endothelial cells) were investigated. The effect of NGR-M-PTX on
      BMEC proliferation and the cytotoxicity of NGR-M-PTX in C6 glioma cells were also
      tested. The antitumor activity NGR-M-PTX was evaluated in C6 glioma tumor-bearing
      rats in vivo. The particle size of NGR-M-PTX was approximately 54.2 nm. The drug
      encapsulation efficiency of NGR-M-PTX was 82.11 +/- 2.82%. The cellular coumarin
      6 level of NGR-M-coumarin-6 in the BMEC was about 2.2-fold higher than that of M
      coumarin-6. BMEC proliferation was significantly inhibited by NGR-M-PTX. NGR-M
      PTX had a much lower IC(50) value than M-PTX and free drug. The growth of C6
      glioma tumor was markedly inhibited by NGR-M-PTX compared with Taxol. In
      conclusion, our results show that antiangiogenic therapy using NGR-M-PTX exhibits
      potent in vivo antitumor activity in a C6 glioma-bearing animal model.

PMID- 20677915
TI  - Robot-assisted pyeloplasty: follow-up of first Canadian experience with
      comparison of outcomes between experienced and trainee surgeons.
AB  - BACKGROUND AND PURPOSE: Robot-assisted pyeloplasty (RAP) has been established
      recently as an option in the management of ureteropelvic junction obstruction
      (UPJO). We present the first Canadian experience with RAP with respect to
      operative results and outcomes. We compare the surgical outcomes between
      experienced and trainee surgeons, with respect to operating room times and
      success rates. PATIENTS AND METHODS: Eighty-eight patients underwent
      transperitoneal RAP for UPJO using the da Vinci robotic platform. Two surgeons
      performed Anderson-Hynes dismembered pyeloplasty in 85 cases and YV-plasty in 5
      cases. Five patients had RAP for secondary UPJO after failure of other
      treatments. Diuretic renography was performed at 6 weeks, and 6, 12, 18, 24, and
      36 months postpyeloplasty. The mean follow-up was 14.1 +/- 8.5 months. RESULTS:
      The mean operative time was 167.7 +/- 43.2 minutes, and the mean anastomotic time
      was 41.9 +/- 14.1 minutes. The mean operative duration significantly decreased
      with time (P < 0.05). Ten patients needed simultaneous nephroscopic stone
      management via the pyelotomy incision. The mean blood loss was 56.6 +/- 55.4 mL,
      and the mean hospital stay was 2.5 +/- 0.5 days. There were five major
      postoperative (stent migration, urinoma) and three minor complications that were
      associated with the RAP procedures. Postoperative renal scintigraphy demonstrated
      only four cases with persistent obstruction. Eighty-three (94.3%) patients
      experienced improvement of symptoms whereas 5 continued to be symptomatic. Two
      patients needed secondary procedures to relieve persisting obstruction. There
      were no statistical differences in outcomes between the experienced surgeons and
      trainees (P = 0.28). CONCLUSIONS: In the first large case series of RAP from
      Canada, we demonstrate that RAP can be performed with relatively short operative
      times and is safe and effective, achieving similar long-term results with
      standard open repair. We show that robot-assisted surgery can be safely
      transitioned to surgical trainees. With its cost and availability, its role in
      the Canadian system needs further study.

PMID- 20677916
TI  - A controlled, randomized, head-to-head comparison of the Prolieve
      thermodilatation System versus the Targis System for benign prostatic
      hyperplasia: safety, procedural tolerability, and clinical results.
AB  - PURPOSE: Compare safety and tolerability of the Prolieve((r)) System with the
      Targis((r)) System using objective and subjective measures. PATIENTS AND METHODS:
      Thirty-four men with symptomatic benign prostatic hyperplasia (BPH) were
      randomized to a single treatment with either the Prolieve or Targis system; 30
      were treated and then followed for 6 months. After post-treatment bladder fill
      with >=200 mL saline, patients were catheterized if they could not void after 2
      hours or had a postvoid residual >150 mL. Catheter use, visual analog scale (VAS)
      tolerability scores, American Urological Association scores, and safety were
      assessed. RESULTS: After treatment, 15/16 (94%) Prolieve patients remained
      catheter-free compared with 3/14 (21%) Targis patients (P = 0.0001). Foley
      catheter indwelling time was 58.8 hours for the one Prolieve patient compared
      with 103.9 hrs (range 54-270 h) for the Targis patients (n = 9). Targis patients'
      catheterization requirements were: Seven Foley only, two intermittent self
      catheters only, and two needing both. Intermittent self-catheterization continued
      for 1 month in two Targis patients. VAS tolerability scores were 24% to 50% lower
      during Prolieve treatment vs Targis (P < 0.05). Mean AUA scores for Prolieve
      improved from 21.2 at baseline to 12.3 and 7.9 at week 2 and month 6,
      respectively; for Targis, AUA scores improved from 22.9 at baseline to 17.9 and
      10.9, respectively (P > 0.05). Overall, the incidence of device-related adverse
      events was 31% (Prolieve) compared with 64% (Targis) (P > 0.05)-most prevalently,
      urinary retention, dysuria, and hematuria. No device-related serious adverse
      events occurred. CONCLUSIONS: Prolieve provided enhanced near-term therapeutic
      benefit over Targis as assessed by catheterization, tolerability, and symptom
      relief, which may assist physician and patient decision-making when selecting an
      office-based transurethral microwave therapy option for patients.

PMID- 20677917
TI  - Preparation, characterization, and antitumor activity of paclitaxel-loaded folic
      acid modified and TAT peptide conjugated PEGylated polymeric liposomes.
AB  - Targeting therapy is a promising strategy for enhancing the therapeutic potential
      of chemotherapeutic agents. In this study, we report the construction of a
      multifunctional drug delivery system, termed folic acid modified and TAT peptide
      conjugated PEGylated polymeric liposomes (FA-TATp-PLs), which is originally
      derived from octadecyl-quaternized lysine modified chitosan and cholesterol. Our
      data revealed that FA-TATp-PLs have a particle size of about 60 nm with a zeta
      potential of about 30 mV, a low burst release effect within the first day, a
      sustained release for the next 14 days in vitro as well as an instant cellular
      uptake by folate receptor-overexpressing KB human nasopharyngeal carcinoma cells.
      In vitro cytotoxicity of paclitaxel-loaded FA-TATp-PLs in KB cells was superior
      to that of Taxol((r)). Furthermore, a comparable antitumor efficacy of paclitaxel
      loaded FA-TATp-PLs and Taxol((r)) was observed at the same doses in murine models
      bearing nasopharyngeal carcinoma. These results demonstrate that the paclitaxel
      formulation not only exhibits a higher antitumor activity but also significantly
      reduces the toxicity and improves the bioavailability as compared to that of free
      paclitaxel for the treatment of nasopharyngeal carcinoma. Taken together, our
      findings indicate that paclitaxel-loaded FA-TATp-PLs are a promising nano-sized
      drug formulation for future cancer therapy.

PMID- 20677918
TI  - Detection, molecular characterization, and clonal diversity of methicillin
      resistant Staphylococcus aureus CC398 and CC97 in Spanish slaughter pigs of
      different age groups.
AB  - The objective of this study was to determine the frequency of nasal carriage of
      methicillin-resistant Staphylococcus aureus (MRSA) in slaughter pigs, to
      characterize the recovered isolates, and to investigate their genomic
      relatedness. Nasal swabs were collected from 53 finishing-pigs (F-pigs) and 53
      suckling-piglets (S-piglets) at two different abattoirs in La Rioja (Northern
      Spain) coming from six production holdings. MRSA isolates were characterized by
      spa-, agr-, SCCmec-, and multilocus sequence typing, pulsed-field gel
      electrophoresis (PFGE)-ApaI, toxin gene profiling, antimicrobial susceptibility,
      and determination of antimicrobial resistance genes. MRSA isolates were recovered
      from 11 F-pigs (14 isolates) and 26 S-piglets (30 isolates). Forty of the 44MRSA
      presented the spa-types t011, t108, t1197, and t2346, which corresponded to the
      sequence type ST398 and to the clonal complex CC398. Interestingly, the remaining
      four isolates from F-pigs presented the spa-type t3992, and they were ascribed to
      a new sequence type named ST1379 (a single-locus variant of ST97), which was
      included in clonal complex CC97. Five PFGE-ApaI clusters with up to nine
      individual patterns detected among our MRSA and low genomic relatedness was
      observed between F-pig and S-piglet isolates. All MRSA were positive for hla,
      hld, and hlg hemolysin genes. ST1379 isolates harbored eta, lukE/D, and hlg-2
      toxin genes, whereas ST398 isolates were positive for hlb. A great variety of
      distinct resistance gene patterns were observed, most of them coming from F-pig
      isolates. MRSA virulence properties seem to be dependent of the isolate clonal
      lineage. This study showed that slaughter pigs are frequently colonized by MRSA
      CC398; moreover, the detection of strains belonging to CC97 underlines that other
      lineages are also able to spread in livestock. Further studies should assess the
      risk of CC398 and non-CC398 MRSA to enter the food chain as well as the human
      health implications.

PMID- 20677919
TI  - Human Barrett's adenocarcinoma of the esophagus, associated myofibroblasts, and
      endothelium can arise from bone marrow-derived cells after allogeneic stem cell
      transplant.
AB  - This study characterizes the contribution of bone marrow-derived cells (BMDCs) to
      Barrett's adenocarcinoma of the esophagus using a mouse surgical model of disease
      and human specimens. Transplantation of bone marrow expressing beta galactosidase
      into a wild-type mouse, followed by surgical esophagojejunostomy, allowed
      tracking of BMDCs into the surgical anastomosis and resulting Barrett's
      metaplasia. Human tissue from a male patient who had been transplanted with
      female bone marrow and later developed esophageal adenocarcinoma allowed us to
      tract donor-derived cells into the tumor. Using a combination of antibodies
      directed against beta-galactosidase (animal studies) and X/Y fluorescent in situ
      hybridization (FISH) (human studies), combined with specific lineage staining
      directed against epithelial, fibroblast, endothelial, and leukocyte markers, we
      show that bone marrow cells contribute to both the epithelial and stromal
      component of esophageal adenocarcinoma. These findings demonstrate that BMDCs can
      generate cancer-associated fibroblasts as well as contribute directly to
      epithelial cells in cancer of the esophagus.

PMID- 20677920
TI  - Does serum soluble vascular endothelial growth factor levels have different
      importance in pediatric acute leukemia and malignant lymphoma patients?
AB  - Vascular endothelial growth factor (VEGF) seems to play a central role in
      angiogenesis-lymphangiogenesis in hematological malignancies. There are limited
      data related to childhood hematologic malignancies. The aim of the study was to
      evaluate soluble VEGF (sVEGF) levels in children with acute leukemia and
      malignant lymphoma (ML) at diagnosis and in remission. The levels of serum sVEGF
      were measured by enzyme-linked immunosorbent assay (ELISA) in 20 children with
      acute leukemia, 33 children with different histopathological subtypes of ML, and
      20 healthy controls. The levels of sVEGF at diagnosis (range 2 -1040 pg/mL;
      median 52 pg/mL) was significantly lower than in remission (range 136 -1960
      pg/mL; median 630 pg/mL) in acute myeloid leukemia (AML) group (P = .018). The
      sVEGF levels at diagnosis (range: 2 -640 pg/mL; median 89 pg/mL) was
      significantly lower compared to remission values (range: 116 -1960 pg/mL; median
      136 pg/mL) in patients with acute lymphoblastic leukemia (ALL) (P = .002). In ML
      group, including Burkitt's lymphoma (BL), T-cell non-Hodgkin's lymphoma (NHL),
      and Hodgkin's lymphoma (HL), sVEGF levels at diagnosis were higher than remission
      levels, but there was no statistically significant difference (P >.05). On the
      other hand, there were significant difference between levels in active disease
      and control group, ie, BL versus control, T-cell NHL versus control, and HL
      versus control (P = .008, P = .043, P = .007, respectively). The authors noticed
      that sVEGF levels showed distinct behavioral pattern in different childhood
      malignancies at diagnosis and in remission. In acute leukemia and ML patients,
      VEGF acts through different pathophysiological mechanisms, in both bone marrow
      (BM) angiogenesis and lymphoid tissue lymphangiogenesis.

PMID- 20677921
TI  - Oral lorazepam prevents seizure during high-dose busulfan in children undergoing
      hematopoietic stem cell transplantation: a prospective study.
AB  - High-dose Busulfan in combination chemotherapy has been used commonly for
      hematopoietic stem cell transplantation. It crosses the blood-brain barrier and
      could cause seizure. Benzodiazepines have been used as anticonvulsant
      prophylaxis. This is a prospective study using oral lorazepam together with
      busulfan-based conditioning regimen in 30 children undergoing hematopoietic stem
      cell transplantation. The dose of lorazepam used ranged from 0.017 to 0.039 mg/kg
      (median = 0.026 mg/kg) per dose. None of the patients developed seizure while
      receiving oral lorazepam or within 72 hours of the last dose of Busulfan. Oral
      lorazepam was tolerated by the patients, but all patients needed dose reduction
      due to some adverse effects. In the authors' experience, oral lorazepam is a
      useful anticonvulsant prophylaxis for children receiving high-dose busulfan.

PMID- 20677922
TI  - Neuroblastoma presented with polyhydramniosis.
AB  - Neuroblastoma is the most common extracranial solid tumor in pediatric age group.
      Clinical presentation of neuroblastoma is mostly related to origin of the tumor,
      extent of disease, and the presence of paraneoplastic syndromes. Here the authors
      report a neonate with neuroblastoma with an atypical presentation, diagnosed with
      postnatal abdominal ultrasonography performed due to polyhydramniosis in her
      mother during pregnancy.

PMID- 20677923
TI  - Fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin
      (FLAG-IDA) for the treatment of children with poor-prognosis acute leukemia: the
      Hacettepe experience.
AB  - Fludarabine, cytarabine, granulocyte colony-stimulating factor (G-CSF), and
      idarubicin (FLAG-IDA) regimen has been proven to be a potentially useful
      chemotherapy regimen for relapsed or poor-prognosis childhood leukemia. The aim
      of the study was to evaluate complete remission (CR) rate, toxicity, and overall
      survival of children with poor-prognosis acute leukemia who received the FLAG-IDA
      regimen. Furthermore, the authors investigated the children who achieved CR
      following FLAG-IDA treatment regarding their eligibility for allogeneic
      hematopoietic stem cell transplantation (HSCT). Between January 2002 and April
      2007, 25 children with poor-prognosis acute leukemia were treated with FLAG-IDA
      regimen in our center. Of the 25 children (16 AML, 9 ALL) with poor-prognosis
      acute leukemia, 7 (28.0%) received 1 cycle, 17 (68.0%) received 2 cycles, and 1
      (4%) received 3 cycles of FLAG or FLAG-IDA regimen. After 44 cycles of FLAG-IDA
      or FLAG regimen, 10/25 (40%) children were nonresponders, 15/25 (60.0%) showed
      CR. Five (20%) of these patients in CR who underwent allogeneic HSCT are still in
      remission. The remaining 20 (80.0%) children were lost due to infection or
      relapse of the primary diseases. The overall survival of patients who are still
      alive and underwent allogeneic HSCT (mean: 40.6 +/- 4.7, median: 40, range: 34-46
      months) was longer than that of patients (mean: 5.5 +/- 4.3, median: 4, range: 1
      15 months) who did not undergo allogeneic HSCT. The CR rate was quite high in the
      present study using the FLAG-IDA regimen, and the authors believe this regimen is
      a possible option prior to allogeneic HSCT in children with poor-prognosis acute
      leukemia.

PMID- 20677924
TI  - Sacral mesenchymal chondrosarcoma in childhood: a case report and review of the
      literature.
AB  - Mesenchymal chondrosarcomas are rare malignant tumors in pediatric age group. The
      authors present a case of mesenchymal chondrosarcoma located in the sacrum in a
      10-year-old-girl that was successfully treated with chemotherapy and radiotherapy
      after surgical excision. According to the authors' literature search, the patient
      is the first reported case of pediatric sacral primary mesenchymal
      chondrosarcoma. Mesenchymal chondrosarcoma cases in pediatric age group published
      in English literature was reviewed.

PMID- 20677925
TI  - The role of Treg cells and FoxP3 expression in immunity of beta-thalassemia major
      AND beta-thalassemia trait patients.
AB  - There is increased susceptibility to infections in beta-thalassemia. Changes in T
      and B-lymphocyte subsets and functions, defective chemotaxis, and phagocytosis
      of neutrophils and macrophages have been described in these patients. Regulatory
      T cells (Treg cells) play a crucial role in the maintenance of immunological self
      tolerance. The FOXP3 gene is specifically expressed on Treg cells. Increased
      antigenic stimuli due to repeated blood transfusions might change the Treg cells
      and FOXP3 percentage in beta-thalassemia. Immune functions of peripheral blood
      lymphocytes, percentage of Treg cells (defined as CD4(+)CD25(+)FoxP3(+)) were
      evaluated in 30 beta-thalassemia major, 30 beta-thalassemia trait, and 20 healthy
      children. Percentage of CD4(+)CD45RA(+) cells were increased in beta-thalassemia
      trait compared to both beta-thalassemia major and controls, whereas percentage of
      CD4(+)CD45RO(+) cells were higher in beta-thalassemia major and trait patient
      compared to controls. Percentages of CD4(+)CD25(bright) and CD4(+)CD25(+)FoxP3(+)
      Treg cells were increased only in beta-thalassemia major patients compared to
      controls (P = .001 and P = .0001, respectively). T lymphocytes express activated
      phenotype both in beta-thalassemia major and trait patients. However, only in
      beta-thalassemia major patients who were exposed to chronic antigenic stimulus as
      a result of repeated blood transfusions was an increase observed in Treg cells,
      which might suppress immune activation status.

PMID- 20677926
TI  - Amniotic fluid cells are more efficiently reprogrammed to pluripotency than adult
      cells.
AB  - Recently, cultured human adult skin cells were reprogrammed to induced
      pluripotent stem (iPS) cells, which have characteristics similar to human
      embryonic stem (hES) cells. Patient-derived iPS cells offer genetic and
      immunologic advantages for cell and tissue replacement or engineering. The
      efficiency of generating human iPS cells has been very low; therefore an easily
      and efficiently reprogrammed cell type is highly desired. Here, we demonstrate
      that terminally differentiated human amniotic fluid (AF) skin cells provide an
      accessible source for efficiently generating abundant-induced pluripotent stem
      (AF-iPS) cells. By induction of pluripotency with the transcription factor
      quartet (OCT3/4, SOX2, KLF4, and c-MYC) the terminally differentiated, cultured
      AF skin cells formed iPS colonies approximately twice as fast and yielded nearly
      a two-hundred percent increase in number, compared to cultured adult skin cells.
      AF-iPS cells were identical to hES cells for morphological and growth
      characteristics, antigenic stem cell markers, stem cell gene expression,
      telomerase activity, in vitro and in vivo differentiation into the three germ
      layers and for their capacity to form embryoid bodies (EBs) and teratomas. Our
      findings provide a biological interesting conclusion that these fetal AF cells
      are more rapidly, easily, and efficiently reprogrammed to pluripotency than
      neonatal and adult cells. AF-iPS cells may have a "young," more embryonic like
      epigenetic background, which may facilitate and accelerate pluripotency. The
      ability to efficiently and rapidly reprogram terminally differentiated AF skin
      cells and generate induced pluripotent stem cells provides an abundant iPS cell
      source for various basic studies and a potential for future patient-specific
      personalized therapies.

PMID- 20677927
TI  - Latrunculin A dramatically improves the developmental capacity of nuclear
      transfer embryos derived from gene-modified clawn miniature pig cells.
AB  - This study was carried out to examine the effect of postactivation treatment with
      latrunculin A (LatA), an actin polymerisation inhibitor, on in vitro and in vivo
      development of somatic cell nuclear transfer (SCNT) embryos derived from gene
      modified Clawn miniature pig cells. After the fusion and activation, SCNT embryos
      were treated with or without a cytoskeletal inhibitor [LatA or 10.4 microM
      cytochalasin B (CB) for 2 h]. The cleavage rate was significantly higher (p <
      0.05) in embryos exposed to 0.5 microM LatA than those in embryos exposed to CB
      and without a cytoskeletal inhibitor. Moreover, the blastocyst formation rate was
      significantly higher (p < 0.05) in embryos exposed to 0.5 or 1 microM LatA than
      those in embryos exposed to CB and without a cytoskeletal inhibitor. In addition,
      five fetuses were obtained from recipient uteri after transfer of embryos treated
      with 0.5 muM LatA. The results of this study show for the first time that
      postactivation treatment with LatA is effective to improve in vitro developmental
      capacity of gene-modified cloned miniature pig embryos and embryos treated with
      LatA have the ability to develop into fetuses.

PMID- 20677928
TI  - The comparison between conditioned media and serum-free media in human embryonic
      stem cell culture and differentiation.
AB  - Human embryonic stem cells (hESCs) offer an inexhaustible supply of human somatic
      cell types through their ability to self-renew while retaining pluripotency. As
      such, hESC-derived cell types are important for applications ranging from in
      vitro modeling to therapeutic use. However, for their full potential to be
      realized, both the growth of the undifferentiated cells and their derivatives
      must be performed in defined culture conditions. Many research groups maintain
      hESCs using mouse embryonic fibroblasts (MEF) and MEF conditioned medium (CM).
      The use of murine systems to support hESCs has been imperative in developing hESC
      technology; however, they suffer from some major limitations including lack of
      definition, xenobiotic nature, batch-to-batch variation, and labor-intensive
      production. Therefore, hESC culture definition is essential if hESC lines, and
      their derivatives are to be quality assured and manufactured to GMP. We have
      initiated the process of standardizing hESC tissue culture and have employed two
      serum-free media: mTeSR (MT) and Stem Pro (SP). hESCs were maintained in a
      pluripotent state, for over 30 passages using MT and SP. Additionally, we present
      evidence that hESCs maintained in MT and SP generate equivalent levels of human
      hepatic endoderm as observed with CM. This data suggests that MT and SP are
      effective replacements for MEF-CM in hESC culture, contributing to the
      standardization of hESC in vitro models and ultimately their application.

PMID- 20677929
TI  - Growth and hematologic characteristics of cloned dogs derived from adult somatic
      cell nuclear transfer.
AB  - Three viable female dogs, which have the same genotype, have been successfully
      produced by somatic cell nuclear transfer (SCNT); however, data on the growth
      pattern of cloned dogs are lacking. Thus, the aim of this study was (1) to assess
      growth parameters among those cloned dogs with measurement of body weight,
      height, and radiographic analysis of skull size and bone plate, and (2) to
      compare hematologic characteristics among the donor dog, cloned dogs, and age
      matched control dogs. The cloned dogs were kept in the same environmental
      conditions. The body weight increased from 0.52, 0.46, and 0.52 kg at birth to
      21.9, 22.9, and 20.4 kg at 68 weeks of age for individual cloned dogs,
      respectively. The withers height increased from 34.5, 32.6, and 35.2 cm at 8
      weeks of age to 67.1 cm at 68 weeks of age in the three clones. The radiographic
      data demonstrated that patterns of bone growth were similar among cloned dogs,
      and all measured parameters of matured cloned dogs were similar with that of the
      fully grown donor dog. An age-specific pattern was identified on hematologic and
      serum biochemical measurements in both cloned dogs and age-matched controls. The
      parameters examined were within the normal reference ranges for healthy dogs. In
      conclusion, three genetically identical cloned dogs showed similar growth
      characteristics and had normal hematological and serum biochemical parameters.

PMID- 20677930
TI  - Culture conditions and enzymatic passaging of bovine ESC-like cells.
AB  - The goals of the current study were to (1) improve culture conditions and (2)
      chemical passaging of bovine embryonic stem cell-like (bESC-like) cells.
      Specifically, the effects of human leukemia inhibitory factor (hLIF), two types
      of feeders, mouse embryonic fibroblast (MEF) and bovine embryonic fibroblast
      (BEF), as well as three different enzymatic treatments including Trypsin-EDTA,
      TrypLE, and Liberase Blendzymes 3 were investigated. The addition of hLIF at 1000
      U/mL to the culture medium (41.2 and 36.9%), and the use of either MEF or BEF
      feeders (40.3 and 38.1%) had no significant effect on the ability of inner cell
      masses (ICMs) to form primary cell colonies compared to controls. All bESC-like
      cells were first dissociated mechanically for three passages followed by
      enzymatic dissociation. The ability to maintain ESC morphology to passage 10 was
      compared among the three enzymes above. More bESC-like cell lines survived beyond
      passage 10 when treated with TrypLE compared to Trypson-EDTA (28.8 and 12.6%; p <
      0.05), and bESC-like cells differentiated quickly when treated with Liberase
      Blendzyme 3. The bESC-like cells generated in our study displayed typical stem
      cell morphology and expressed specific markers such as SSEA-1, AP, OCT-4, and
      Nanog. When removed from feeders, these bESC-like cells formed embryoid bodies
      (EBs) in a suspension culture. When EBs were cultured on tissue culture plates,
      they differentiated into various cell types. In summary, we were able to culture
      bESC-like cells more than 10 passages by enzymatic dissociation, which is
      important in gene targeting, maintenance, and banking of bESC lines.

PMID- 20677932
TI  - Effect of human chorionic gonadotropin and progesterone administration on the
      developmental potential of mouse somatic cell nuclear-transferred oocytes.
AB  - Somatic cell nuclear-transferred (SCNT) oocytes have a relatively high potential
      to develop into blastocysts in vitro, but a large proportion embryos die at
      various pre- and postimplantation stages after transfer to recipients. Although
      the reason for the high mortality of SCNT embryos at the peri- and
      postimplantation stages is not clear, epigenetic abnormalities of SCNT embryos
      are considered to be the main cause. Such abnormalities of SCNT embryos may
      decrease their ability to maintain the corpora lutea, which is necessary for
      initiating implantation and maintaining fetal development. To examine this
      hypothesis, human chorionic gonadotropin (hCG) and progesterone were administered
      at different times to recipients that received SCNT embryos. When hCG was
      administered daily from day 3.5 to day 6.5 of pregnancy, the implantation and
      fetal development rates increased significantly compared to those of controls.
      The potential of SCNT embryos to develop to full term, however, was not greater
      than that of controls, even if hCG administration was continued to day 11.5 or
      day 17.5 and progesterone was administered from day 7.5 to day 17.5 after hCG
      injection. These findings demonstrated that administering hCG to recipients
      protects the in vivo development of SCNT embryos until day 10.5, but other
      treatment is necessary to support the progression of the embryos to full-term
      development.

PMID- 20677931
TI  - Quantification of leukocyte genomic 5-methylcytosine levels reveals epigenetic
      plasticity in healthy adult cloned cattle.
AB  - Successful somatic cell nuclear transfer (SCNT) requires epigenetic reprogramming
      of a differentiated donor cell nucleus. Incorrect reprogramming of epigenetic
      markings such as DNA methylation is associated with compromised prenatal
      development and postnatal abnormalities. Clones that survive into adulthood, in
      contrast, are assumed to possess a normalized epigenome corresponding to their
      normal phenotype. To address this point, we used capillary electrophoresis to
      measure 5-methylcytosine (5mC) levels in leukocyte DNA of 38 healthy female
      bovine clones that represented five genotypes from the Simmental breed and four
      genotypes from the Holstein breed. The estimated variance in 5mC level within
      clone genotypes of both breeds [0.104, 95% confidence interval (CI): 0.070-0.168]
      was higher than between clone genotypes (0, CI: 0-0.047). We quantified the
      contribution of SCNT to this unexpected variability by comparing the 19 Simmental
      clones with 12 female Simmental monozygotic twin pairs of similar age. In
      Simmental clones, the estimated variability within genotype (0.0636, CI: 0.0358
      0.127) was clearly higher than in twin pairs (0.0091, CI: 0.0047-0.0229). In
      clones, variability within genotype (0.0636) was again higher than between
      genotypes (0, CI: 0-0.077). Twins, in contrast, showed lower variability within
      genotypes (0.0091) than between genotypes (0.0136, CI: 0.00250-0.0428).
      Importantly, the absolute deviations of 5mC values of individual SCNT clones from
      their genotype means were fivefold increased in comparison to twins. Further
      comparisons with noncloned controls revealed DNA hypermethylation in most of the
      clones. The clone-specific variability in DNA methylation and DNA
      hypermethylation clearly show that healthy adult SCNT clones must be considered
      as epigenome variants.

PMID- 20677933
TI  - Myogenesis is delayed in bovine fetal clones.
AB  - We have recently reported that maturation of the skeletal muscle is delayed in
      cloned calves during their first year postnatally. This delay could originate
      from perturbations in fetal myogenesis. The aim of this study was to evaluate the
      developmental characteristics of muscle in clones versus animals derived from
      conventional reproduction. We have characterized the anatomical and biochemical
      properties of the Semitendinosus muscle of clones versus controls at day 60 and
      day 260. We have analyzed the contractile and metabolic properties of muscle
      fibers by measuring the abundance of myosin heavy chain (MyHC) isoforms and
      activities of metabolic enzymes (LDH, PFK, COX, CS, ICDH), respectively. The
      spatial repartition of some components of the extracellular matrix (collagen
      types I, IV, VI, chondroitin-6-sulfate, decorin, and tenascin-X) was also
      studied. At day 60 we found lower numbers and structural organization of fibers,
      and a delay in the setup of the extracellular matrix. IGF-2 transcript abundance
      was lower in clones than in their controls. There was no difference in the
      expression of VEGF (a growth factor regulating vascularization and myogenesis)
      and its receptor. At day 260 the muscles of fetal clones have not reached the
      same degree of differentiation than controls as shown by their lower energy
      metabolisms and their MyHC pattern. These results show for the first time that
      disturbances in myogenesis occur early in fetal life in cloned cattle.

PMID- 20677934
TI  - Efficient derivation of embryonic stem cells from nuclear transfer and
      parthenogenetic embryos derived from cryopreserved oocytes.
AB  - Deriving histocompatible embryonic stem (ES) cells by somatic cell nuclear
      transfer (SCNT) and parthenogenetic activation (PA) requires fresh oocytes, which
      prevents their applications in humans. Here, we evaluated the efficiency of
      deriving ES cells from mature metaphase II (MII) and immature metaphase I (MI)
      vitrified oocytes, by PA or SCNT, in a mouse model. We successfully generated ES
      cell lines from PA (MII and MI) and SCNT (MII and MI) blastocysts. These cell
      lines expressed genes and antigens characteristic of pluripotent ES cells and
      produced full-term pups upon tetraploid embryo complementation. This study
      established an animal model for efficient generation of patient-specific ES cell
      lines using cryopreserved oocytes. This is a major step forward in the
      application of therapeutic cloning and parthenogenetic technology in human
      regenerative medicine and will serve as an important alternative to the iPS cell
      technology in countries/regions where these technologies are permitted.

PMID- 20677935
TI  - Aberrant expression and methylation status of putatively imprinted genes in
      placenta of cloned piglets.
AB  - Unlike embryos derived from fertilization, most cloned embryos die during
      postimplantation development, and those that survive to term are frequently
      defective. Many of the observed defects involve placenta. Abnormal placentation
      has been described in several cloned species. Imprinted genes are important
      regulators of placenta growth, and may be subjected to faulty reprogramming
      during somatic cell nuclear transfer. We aimed to determine the expression levels
      and methylation patterns of imprinted genes in placentas of live cloned piglets
      and dead ones. Quantitative real-time reverse transcriptase-polymerase chain
      reaction (RT-PCR) analysis showed that the expression of all four imprinted genes
      (IGF2, H19, PEG3, and GRB10) was significantly reduced in placentas of dead
      clones compared with placentas of live cloned piglets and controls (p < 0.05). In
      contrast, both live and dead cloned piglets exhibited steady-state mRNA levels
      for these genes within the control range (p > 0.05). Transcript levels for these
      genes in live clones rarely differed from those of controls in both piglets and
      placentas. Examination of the methylation status of DMR2 of IGF2 and CTCF3 of H19
      genes revealed that both genes exhibited significant high methylation levels in
      placentas of dead clones compared with placentas of live clones and controls. In
      contrast, both genes showed a normal differential methylation pattern in live
      cloned piglets and their placentas compared with controls. Importantly, dead
      cloned piglets also showed a normal pattern. Our results suggest that abnormal
      expression of imprinted genes in placenta may contribute to the development
      failure in pig somatic cell nuclear transfer (SCNT), which may be caused by
      abnormal methylation patterns in differentially methylated regions (DMRs) of
      imprinted genes as a result of incomplete reprogramming during SCNT.

PMID- 20677936
TI  - In vitro and in vivo characterization of putative porcine embryonic stem cells.
AB  - We have developed a new method for the isolation of porcine embryonic stem cells
      (ESCs) from in vivo-derived and in vitro-produced embryos. Here we describe the
      isolation and characterization of several ESC lines established using this
      method. Cells from these lines were passaged up to 14 times, during which they
      were repeatedly cryopreserved. During this time, ESCs maintained their morphology
      and continued to express Oct 4, Nanog, and SSEA1. These cells formed embryoid
      bodies in suspension culture, and could be directed to differentiate into various
      lineages representative of all three germ layers in vitro. When injected into
      blastocysts these cells localized in the inner cell mass of blastocysts. To
      examine their pluripotency further, cells were injected into host blastocysts and
      transferred to recipient animals. Of the six transfers undertaken, one recipient
      became pregnant and gave birth to a litter of one male and three female piglets.
      Microsatellite analysis of DNA extracted from the tail tissue of these piglets
      indicated that two female piglets were chimaeric.

PMID- 20677938
TI  - Detection of European Trichobilharzia schistosomes ( T. franki , T. szidati , and
      T. regenti ) based on novel genome sequences.
AB  - The most frequent causative agents of cercarial dermatitis in Europe are the
      avian schistosomes of the genus Trichobilharzia . They preferably parasitize
      birds of the Anatidae. Trichobilharzia spp. schistosomes are also able to
      penetrate mammalian skin, posing a health risk to mammals, including humans.
      Currently several loci from nuclear and mitochondrial genomes are determined for
      European species of Trichobilharzia . Among them there is 1 genome sequence,
      ToSau3A, which is suitable for detection of Trichobilharzia spp. infection in
      aquatic systems. In the present paper, we used a PCR assay to obtain novel genome
      sequences from cercariae isolates of 3 European bird schistosome species (
      Trichobilharzia franki , Trichobilharzia szidati , and Trichobilharzia regenti )
      collected from freshwater ponds in Belorussia and Russia. We applied RAPD
      fingerprinting using 1 random primer to differentiate 3 trichobilharzian species
      and subsequently cloned and sequenced putative species-specific RAPD fragments.
      One of them (410 bp in length), which was obtained for T. franki , revealed 64%
      homology with the repeat region of Schistosoma mansoni (GenBank FN357352) and
      turned out to be suitable for designing a specific primer pair (TR98F and TR98R)
      to detect 7 novel DNA sequences in the genome of 3 European Trichobilharzia
      species. The newly designed primer pair was found to be potentially suitable for
      PCR-based detection of trichobilharzian infection in snails. PCR primers TR98F
      and TR98R amplified only the DNA isolated from cercariae and sporocysts of 3
      trichobilharzian species, but neither the DNA of 3 other digenean species (
      Bilharziella polonica , Apatemon sp., and Diplostomum sp.) nor the DNA of
      uninfected host snails ( Lymnaea stagnalis , Radix auricularia , and Radix ovata
      ).

PMID- 20677939
TI  - Paucity of initial cerebrospinal fluid inflammation in cryptococcal meningitis is
      associated with subsequent immune reconstitution inflammatory syndrome.
AB  - BACKGROUND: Cryptococcal meningitis (CM)-related immune reconstitution
      inflammatory syndrome (IRIS) complicates antiretroviral therapy (ART) in 20%-40%
      of ART-naive persons with AIDS and prior CM. Pathogenesis is unknown. METHODS: We
      compared initial cerebrospinal fluid (CSF) cultures, inflammatory markers, and
      cytokine profiles in ART-naive patients with AIDS who did or did not subsequently
      develop IRIS after starting ART. We also compared results obtained at IRIS events
      or CM relapse. RESULTS: Of 85 subjects with CM, 33 (39%) developed CM-related
      IRIS and 5 (6%) developed culture-positive CM relapse. At CM diagnosis, subjects
      subsequently developing IRIS had less inflammation, with decreased CSF
      leukocytes, protein, interferon-gamma, interleukin-6, interleukin-8, and tumor
      necrosis factor-alpha, compared with subjects not developing IRIS (P<.05, for
      each). Initial CSF white blood cell counts < or =25 cells/microL and protein
      levels < or =50 mg/dL were associated with development of IRIS (odds ratio, 7.2
      [95% confidence interval, 2.7-18.7]; P<.001). Compared with baseline levels, we
      identified CSF elevations of interferon-gamma, tumor necrosis factor-alpha,
      granulocyte colony-stimulating factor, vascular-endothelial growth factor, and
      eotaxin (CCL11) (P<.05, for each) at the time of IRIS but minimal inflammatory
      changes in those with CM relapse. CONCLUSIONS: Patients who subsequently develop
      CM-related IRIS exhibit less initial CSF inflammation at the time of CM
      diagnosis, compared with those who do not develop IRIS. The inflammatory CSF
      cytokine profiles observed at time of IRIS can distinguish IRIS from CM relapse.

PMID- 20677940
TI  - Impact of interferon-ribavirin treatment on hepatitis C virus (HCV) protease
      quasispecies diversity in HIV- and HCV-coinfected patients.
AB  - Patients with hepatitis C virus (HCV) and human immunodeficiency virus (HIV)
      coinfection for whom prior treatment of HCV with interferon-ribavirin has failed
      may require subsequent treatment with new HCV protease inhibitors (PIs). We
      evaluated the diversity of HCV nonstructural protein 3 (NS3) in 26 HCV- and HIV
      coinfected patients receiving stable antiretroviral therapy (ART) who were
      treated with interferon-ribavirin. Plasma HCV RNA clonal analysis was performed.
      There was greater baseline NS3 diversity in patients with nonresponse or relapse
      than in those with sustained virologic response. Interferon-ribavirin treatment
      did not result in significant changes in HCV protease gene diversity or
      significant HCV PI resistance mutations. The effect of prior interferon-ribavirin
      treatment on HCV NS3 will likely not impact HCV PI efficacy in HIV-coinfected
      patients receiving ART.

PMID- 20677941
TI  - Are host genetics the predominant determinant of persistent nasal Staphylococcus
      aureus carriage in humans?
AB  - BACKGROUND: Staphylococcus aureus nasal carriage is influenced by multifactorial
      interactions which are difficult to study in open populations. Therefore, we
      concomitantly assessed the epidemiological, microbiological, and human-genetic
      carriage-related factors in a nearly closed population. METHODS: In 2006 and
      2008, we collected nasal S. aureus strains, human DNA, and epidemiological data
      from 154 adult Wayampi Amerindians living in an isolated village in the Amazonian
      forest. The genetics of the strains (multilocus sequence type, spa type, and
      toxin-content type), epidemiological risk factors, antibiotic exposure, and
      allelic polymorphism of human genes putatively involved in carriage of the
      persistent carriers were compared with those of other volunteers. RESULTS:
      Overall carriage prevalence was 41.7% in 2006 and 57.8% in 2008, but the overall
      prevalence of persistent carriage was only 26%. The rare and phylogenetically
      distant multilocus sequence type ST1223 was present in 18.5% of the carriers in
      2006 and 34.8% in 2008. No epidemiological factors or antibiotic exposure were
      significantly associated with persistent carriage, but single nucleotide
      polymorphism distribution in C-reactive proteins C2042T and C1184T and
      interleukin-4 C524T genes was significantly associated (P=.02, by global test).
      CONCLUSION: Host genetic factors appeared to be the predominant determinant for
      S. aureus persistent nasal carriage in humans.

PMID- 20677942
TI  - Characterization of antibodies induced by vaccination with hepatitis C virus
      envelope glycoproteins.
AB  - Hepatitis C virus (HCV) envelope glycoproteins E1 and E2 were used with MF59
      adjuvant as a candidate vaccine for a phase 1 safety and immunogenicity trial.
      Ten of 41 vaccinee serum samples displayed a neutralization titer of > or =1:20
      against vesicular stomatitis virus (VSV)-HCV pseudotype, 15 of 36 serum samples
      tested had a neutralization titer of > or =1:400 against human immunodeficiency
      virus (HIV)-HCV pseudotype, and 10 of 36 serum samples tested had a
      neutralization titer of > or =1:20 against cell culture-grown HCV genotype 1a.
      Neutralizing serum samples had increased affinity levels and displayed >2-fold
      higher specific activity levels to well-characterized epitopes on E1/E2,
      especially to the hypervariable region 1 of E2.

PMID- 20677943
TI  - Hepatitis C virus core protein induces homotolerance and cross-tolerance to Toll
      like receptor ligands by activation of Toll-like receptor 2.
AB  - BACKGROUND: Hepatitis C virus (HCV) activates host innate immune responses
      mediated by retinoic acid inducing gene-I (RIG-I) and Toll-like receptors (TLRs).
      Although the nonstructural protein 3/4A (NS3/4A) of HCV disrupts interferon
      responses by inhibiting RIG-I signaling, the effects of TLR activation by HCV
      associated proteins on host innate immune responses are poorly understood.
      METHODS: Proinflammatory cytokine responses to various TLR ligands in human
      antigen-presenting cells (APCs) were examined either with or without
      prestimulation by HCV core protein. RESULTS: TLR2 activation by the HCV core
      protein leads to a decrease in interleukin 6 (IL-6) production by human APCs
      after subsequent stimulation with TLR2 (homotolerance) ligands and TLR4 (cross
      tolerance) ligands. This hyporesponsiveness induced by preexposure to the HCV
      core protein was partially mediated by the negative regulation of nuclear factor
      kappaB activation by the induction of IRAK-M. TLR ligand-induced IL-6 production
      was significantly reduced in peripheral blood monocytes isolated from HCV
      infected patients, compared with those of healthy control subjects. Alloantigen
      presentation by monocytes isolated from HCV-infected patients results in impaired
      production of interleukin 17 by naive CD4(+) T cells in the presence of TLR
      ligands. CONCLUSIONS: Chronic stimulation of APCs with HCV core protein is
      associated with hyporesponsiveness in TLR-mediated innate immunity.

PMID- 20677944
TI  - Adult hospitalizations for laboratory-positive influenza during the 2005-2006
      through 2007-2008 seasons in the United States.
AB  - BACKGROUND: Rates of influenza-associated hospitalizations in the United States
      have been estimated using modeling techniques with data from pneumonia and
      influenza hospitalization discharge diagnoses, but they have not been directly
      estimated from laboratory-positive cases. METHODS: We calculated overall, age
      specific, and site-specific rates of laboratory-positive, influenza-associated
      hospitalization among adults and compared demographic and clinical
      characteristics and outcomes of hospitalized cases by season with use of data
      collected by the Emerging Infections Program Network during the 2005-2006 through
      2007-2008 influenza seasons. RESULTS: Overall rates of adult influenza-associated
      hospitalization per 100,000 persons were 9.9 during the 2005-2006 season, 4.8
      during the 2006-2007 season, and 18.7 during the 2007-2008 season. Rates of
      hospitalization varied by Emerging Infections Program site and increased with
      increasing age. Higher overall and age-specific rates of hospitalization were
      observed during influenza A (H3) predominant seasons and during periods of
      increased circulation of influenza B. More than 80% of hospitalized persons each
      season had > or =1 underlying medical condition, including chronic cardiovascular
      and metabolic diseases. CONCLUSIONS: Rates varied by season, age, geographic
      location, and type/subtype of circulating influenza viruses. Influenza-associated
      hospitalization surveillance is essential for assessing the relative severity of
      influenza seasons over time and the burden of influenza-associated complications.

PMID- 20677945
TI  - Community psychological and behavioral responses through the first wave of the
      2009 influenza A(H1N1) pandemic in Hong Kong.
AB  - BACKGROUND: Little is known about the community psychological and behavioral
      responses to influenza pandemics. METHODS: Using random digit dialing, we sampled
      12,965 Hong Kong residents in 13 cross-sectional telephone surveys between April
      and November 2009, covering the entire first wave of the 2009 influenza A(H1N1)
      pandemic. We examined trends in anxiety, risk perception, knowledge on modes of
      transmission, and preventive behaviors. RESULTS: Respondents reported low anxiety
      levels throughout the epidemic. Perceived susceptibility to infection and
      perceived severity of H1N1 were initially high but declined early in the epidemic
      and remained stable thereafter. As the epidemic grew, knowledge on modes of
      transmission did not improve, the adoption of hygiene measures and use of face
      masks did not change, and social distancing declined. Greater anxiety was
      associated with lower reported use of hygiene measures but greater social
      distancing. Knowledge that H1N1 could be spread by indirect contact was
      associated with greater use of hygiene measures and social distancing.
      CONCLUSIONS: The lack of substantial change in preventive measures or knowledge
      about the modes of H1N1 transmission in the general population suggests that
      community mitigation measures played little role in mitigating the impact of the
      first wave of 2009 influenza A(H1N1) pandemic in Hong Kong.

PMID- 20677946
TI  - Changes in soft tissue nasal widths associated with rapid maxillary expansion in
      prepubertal and postpubertal subjects.
AB  - OBJECTIVE: To evaluate changes in the soft tissue width of the nose induced by
      rapid maxillary expansion (RME). Data on greater alar cartilage (GAC) and alar
      base (AB) widths were compared with a normative sample within the same age range.
      MATERIALS AND METHODS: This prospective study consisted of an RME sample of 79
      patients treated with an RME protocol. Mean age at the start of RME treatment was
      13.5 years; average duration of treatment was 6.7 months. Patients were grouped
      into prepubertal and postpubertal groups based on their cervical vertebral
      maturation (CVM) stage. AB and GAC widths were determined at three separate time
      points. The normative sample consisted of 437 orthodontically untreated whites,
      aged 10-16 years. A repeated measures analysis of variance (ANOVA) was used to
      determine group differences. In addition, independent sample t-tests were used to
      compare posttreatment nasal width values vs the untreated normative sample.
      RESULTS: Increases in AB and GAC widths of the nose in the RME sample were less
      than 1.5 mm. No significant differences were noted in width changes between the
      prepubertal and postpubertal subgroups. Comparisons of T3 values showed that on
      average nasal width increases were greater in the RME group than in untreated
      norms by 1.7 mm for the GAC measure (statistically significant), and by less than
      1 mm for the AB measure. CONCLUSIONS: RME has no significant clinical effects on
      the widths of the apical base and the greater alar cartilage of the nose; no
      differences were observed between the two maturational subgroups.

PMID- 20677947
TI  - Maxillary first molar agenesis and other dental anomalies.
AB  - OBJECTIVE: To explore the association of maxillary first molar agenesis with
      other dental anomalies in Japanese orthodontic patients. MATERIALS AND METHODS: A
      total of 32 subjects with one or two congenitally missing maxillary first molars
      (group M) were selected and divided into group 1M (12 subjects with one maxillary
      first molar missing) and group 2M (20 subjects with two maxillary first molars
      missing). As controls, 32 sex-matched subjects without agenesis of maxillary
      first molars were collected (group C). Panoramic and periapical radiographs,
      cephalograms, study models, intraoral photographs, and anamnestic data were used
      to identify anomalies of permanent teeth. Chi-square, Fisher's exact, Kruskal
      Wallis, and Steel-Dwass tests were used to make statistical comparisons. RESULTS:
      The prevalence rates of tooth agenesis other than the maxillary first molars and
      advanced tooth agenesis, with third molars excluded, were significantly higher in
      group 2M than in group C. The absence of second premolars was most common. The
      prevalence rate of third molar agenesis was significantly higher in groups 1M and
      2M than in group C. The occurrence of symmetrical agenesis of the mandibular
      third molars was particularly notable in group 2M as compared to group 1M, in
      which maxillary third molar agenesis was predominant. There was no significant
      association between maxillary first molar agenesis and other dental anomalies,
      except for agenesis of teeth other than maxillary first molars. CONCLUSION:
      Agenesis of maxillary first molars is associated with a higher prevalence of
      other permanent tooth agenesis and advanced tooth agenesis.

PMID- 20677948
TI  - Cephalometric craniofacial features in Saudi parents and their offspring.
AB  - OBJECTIVE: To estimate the correlation and heritability values of craniofacial
      variables between parents and their offspring. MATERIALS AND METHODS: The sample
      comprised 24 Saudi families; each family consisted of father, mother, son, and
      daughter. Lateral cephalometric radiographs were taken for each family member.
      Twenty-eight angular, linear, and proportional cephalometric variables were
      measured. Interfamilial correlations and heritability (h(2)) values were
      estimated among father-son, father-daughter, mother-son, and mother-daughter
      pairings. RESULTS: The most similar angular measurements between parents and
      offspring were related to mandibular variables, which were as follows: MP-SN
      degrees , MP-FH degrees , SNB degrees , and SNPog degrees ; facial height
      dimensions and mandibular body length were among the highest similar linear
      variables. Lower facial height percentage had greater resemblance to parents with
      regard to proportional measurements. Both the correlation coefficients and the
      heritable values of these characteristics were stronger in the father-offspring
      than the mother-offspring pairings. The daughters' cephalometric craniofacial
      characteristics were more affected by the parents than were those of the sons.
      CONCLUSIONS: The overall correlation and h(2) mean values for the three types of
      measurements showed stronger values in the father-offspring than the mother
      offspring groups, with the father-daughter pairings more significant than the
      father-son groups.

PMID- 20677949
TI  - Change in dental pulp parameters in response to different modes of orthodontic
      force application.
AB  - OBJECTIVES: (1) To evaluate dental pulp sensitivity by electrical pulp testing
      and measure aspartate aminotransferase activity in the pulp after 14 days of
      orthodontic intrusion, and (2) to compare those measurements with measurements
      obtained in teeth after 7 days of intrusion and 7 days of rest. MATERIALS AND
      METHODS: The study sample included 13 subjects (mean age = 16.5 +/- 2.7 years).
      For every subject, before extraction, two contralateral premolars were included
      in a spring and loaded by a force. Two study groups were formed: Group A, teeth
      with 14 days of mechanical load, and Group B, teeth with 7 days of mechanical
      load plus 7 days of rest. Electrical pulp testing and aspartate aminotransferase
      activity measurements were performed after 14 days in all tested teeth. After
      extraction, aspartate aminotransferase activity in the pulp was determined
      spectrophotometrically at 20 degrees C. RESULTS: Mean aspartate aminotransferase
      activity values were 0.21 U/mg (SD = 0.15) in Group A and 0.27 U/mg (SD = 0.17)
      in Group B. Mean electrical pulp testing readings were 38.92 microA (SD = 24.61)
      in Group A and 36.77 microA (SD = 26.84) in Group B. Mean values of the intrusive
      force magnitude did not differ in both groups. CONCLUSIONS: Different durations
      of orthodontic intrusion, defined as 14 days of load and 7 days of load followed
      by 7 resting days, were not reflected by electrical pulp testing or by aspartate
      aminotransferase activity levels in the pulp of the affected teeth. However, the
      response threshold to electrical pulp stimulation was elevated in all tested
      teeth.

PMID- 20677950
TI  - Locating the center of resistance of maxillary anterior teeth retracted by Double
      J Retractor with palatal miniscrews.
AB  - OBJECTIVE: To locate the center of resistance of six maxillary anterior teeth
      retracted by the Double J Retractor (DJR) and to find the optimal position of
      palatal miniscrews. MATERIALS AND METHODS: The three-dimensional (3D) finite
      element model included 12 teeth with two first premolars extracted. The DJR was
      modeled as a 3D beam element. The miniscrew was sagittally placed between the
      second premolar and the first molar, and the vertical position of the miniscrew
      was established at five conditions: 6, 7, 8, 9, and 10 mm apically from the
      cervical line of the first molar. The length of the retraction lever arm was
      determined according to the position of the miniscrew, for the direction of
      retraction force to be parallel to the maxillary occlusal plane. The 3D finite
      element method was used to determine the location of the center of resistance of
      the maxillary anterior teeth by visualizing the tooth displacement and stress
      distribution. RESULTS: As the miniscrew was located apically, the stress spread
      out to the root apex and the adjacent alveolar bone. At the 8-mm level of
      miniscrews, a bodily-like parallel retraction could be obtained with DJR.
      CONCLUSION: In this study, the center of resistance of the six maxillary anterior
      teeth retracted by DJR with palatal miniscrews was estimated to be 12.2 mm
      apically from the incisal edge of the central incisor.

PMID- 20677951
TI  - Effects of CO(2) laser debonding of a ceramic bracket on the mechanical
      properties of enamel.
AB  - OBJECTIVE: To investigate the effects of CO(2) laser debonding of a ceramic
      bracket on the mechanical properties of tooth enamel. MATERIALS AND METHODS:
      Fifty-three human premolars were used in this study. The temperature changes of
      cross-sectioned specimens during laser irradiation were monitored with an
      infrared thermographic microscope system. Different laser output settings (3, 4,
      5, and 6 W) were compared. The shear bond strength of brackets after laser
      irradiation was measured for specimens bonded with a conventional etch and rinse
      adhesive or with a self-etching adhesive, and the adhesive remnant index score
      was calculated. The hardness and elastic modulus of cross-sectioned enamel after
      laser irradiation were investigated by the nanoindentation test. Data were
      compared by one-way and two-way analysis of variance, followed by the Scheffe
      test. RESULTS: The temperature of enamel increased by about 200 degrees C under
      CO(2) laser irradiation with a relatively high output (5 and 6 W), and a
      temperature increase of about 100 degrees C to 150 degrees C was seen under laser
      irradiation with a low output (3 and 4 W). The bracket shear bond strength
      decreased under all laser irradiation conditions. The hardness and elastic
      modulus of enamel were not affected by CO(2) laser debonding. CONCLUSION: CO(2)
      laser debonding may not cause iatrogenic damage to enamel.

PMID- 20677952
TI  - Impulse debracketing compared to conventional debonding.
AB  - OBJECTIVE: To evaluate impulse debonding compared to three conventional methods
      for bracket removal in relation to the damage caused to the enamel surface.
      MATERIALS AND METHODS: Ninety-six osteotomed third molars were randomly assigned
      to two study groups (n = 48) for bracket bonding with either a composite adhesive
      system (CAS) or a glass-ionomeric cement (GIC). These two groups were then each
      randomly divided into four subgroups (n = 12) according to the method of
      debonding using (1) bracket removal pliers, (2) a side-cutter, (3) a lift-off
      debracketing instrument, or (4) an air pressure pulse device. Following debonding
      and corresponding postprocessing with either a finishing bur (CAS) or ultrasound
      (GIC), the enamel surfaces were assessed for damage, adhesive residues, and the
      need for postprocessing using scanning electron microscopy and the Adhesive
      Remnant Index, and the surfaces were compared in terms of mode of removal and
      type of adhesive using Fisher's exact test (alpha = 5%). RESULTS: No significant
      differences were found between the two different types of adhesives (CAS, GIC) in
      terms of the amount of damage to the enamel. Portions of enamel damage were found
      for impulse debonding/0%<bracket removal pliers/4%<lift-off debracketing
      instrument/17%<side-cutter/21%. The highest Adhesive Remnant Index grades were
      seen for impulse debonding. GIC residues after postprocessing using ultrasound
      were seen in 79%, compared to 48% after rotational postprocessing of CAS
      residues. CONCLUSIONS: Impulse debonding provides a good alternative to
      conventional debonding methods, as the adhesion is usually separated at the
      bracket-adhesive interface, thereby avoiding enamel damage, independent of the
      adhesive used.

PMID- 20677953
TI  - Short-term postorthodontic changes in the absence of retention.
AB  - OBJECTIVE: To evaluate short-term postorthodontic tooth movement without
      retention. MATERIALS AND METHODS: Thirty consenting patients participated in the
      study. At the end of active treatment (T(1)), final archwires were removed while
      leaving the fixed appliances on, and alginate impressions were taken. Four weeks
      later (T(2)) a second set of impressions was taken. A clinical examination
      performed at T(2) determined if the fixed appliances could be removed or if
      additional treatment was required. Based on the examination, patients were
      divided into two groups. Patients in group I (n = 13) had their fixed appliances
      removed, while those in group II (n = 17) required additional treatment. The
      American Board of Orthodontics' Objective Grading System scores and the following
      six variables were measured on plaster casts at T(1) and T(2): maxillary and
      mandibular crowding or spacing, overbite, overjet, and mandibular intercanine and
      intermolar widths. Data were analyzed to detect potential changes from T(1) to
      T(2) and to evaluate differences between the groups. RESULTS: Mandibular
      crowding, overjet, and interproximal contacts worsened for the entire sample,
      while marginal ridges, occlusal contacts, and total American Board of
      Orthodontics scores improved. No statistically significant changes were found
      within group I from T(1) to T(2). Mandibular crowding, overbite, overjet,
      alignment/rotations, and interproximal contacts worsened within group II from
      T(1) to T(2), while marginal ridges and occlusal contacts improved. Significant
      differences were noted between the groups in terms of alignment/rotations,
      interproximal contacts, and mandibular intercanine width. CONCLUSION: Short-term
      postorthodontic tooth movement without retainers demonstrated improvement in
      specific characteristics of the occlusion but negatively affected alignment and
      interproximal contacts in the sample.

PMID- 20677954
TI  - Bone inductive proteins to enhance postorthodontic stability.
AB  - OBJECTIVES: To evaluate the use of bone morphogenetic proteins to enhance
      postorthodontic stability in sheep and to develop a biological method of
      postorthodontic retention. MATERIALS AND METHODS: First incisors were extracted
      in four mature and healthy sheep, and the second incisors were tipped
      reciprocally toward the midline and then retained. Dried bone matrix was injected
      into the distal periodontal space of the left second incisor. The right second
      incisor was left as a control. Both incisors were retained in the tipped position
      for 4 weeks. Then, the orthodontic appliance was removed and the teeth were left
      without retention. Six weeks later, the animals were killed and serial sections
      were prepared for histologic observation. RESULTS: Unlike the control, the
      experimental second incisor maintained its tipped position with minimal relapse.
      On the distal periodontal space of the experimental tooth, areas of focal fusion
      between newly formed bone and newly formed areas of hypercementosis were
      observed. In the distal periodontal space of the control tooth, osteoclastic
      activity was observed along most of the socket wall, and the periodontal space
      appeared narrow and compressed. This brought the tooth close to the boundary of
      the alveolar bone, confirming the relapse observed on that side. CONCLUSION: This
      study proposes a new method of retention in which a biologically safe
      osteoinductive material is used to retain the teeth via induction of points of
      approximation between the cementum and alveolar bone.

PMID- 20677955
TI  - Sagittal mandibular development effects on the dimensions of the awake pharyngeal
      airway passage.
AB  - OBJECTIVE: To test the hypothesis that sagittal mandibular development has no
      effects on the dimensions of the awake pharyngeal airway passage. MATERIALS AND
      METHODS: Ninety-one subjects (age 15-25 years) with a normal vertical growth
      pattern of the mandible, normally positioned maxilla, and various sagittal
      mandibular developments were divided into three groups based on the sagittal
      mandibular development. Group I included 37 subjects who had a normally
      positioned mandible (76 degrees < or = angle between 'S,' 'N,' and 'B'; it
      represents the antero-posterior position of the maxilla in relation to the
      anterior cranial base [SNB] < or = 82 degrees ), Group II included 31 subjects in
      whom the mandible was retrognathic (SNB < 76 degrees ), and Group III included 23
      subjects in whom the mandible was prognathic (SNB > 82 degrees ) in relation to
      the anterior cranial base. Lateral cephalograms were traced manually to evaluate
      the pharyngeal airway passage. RESULTS: The length of the soft palate was
      significantly smaller in mandibular prognathism subjects than in subjects with
      mandibular retrognathism (P < .01). The thickness of the soft palate was
      significantly greater among subjects with mandibular prognathism than in subjects
      with normal (P < .01) and retrognathic (P < .001) mandibular development. The
      sagittal mandibular development had no effect on the dimensions of the
      nasopharyngeal and hypopharyngeal airway passage. The depth of the oropharynx was
      comparable among the subjects with normal and retrognathic mandibles but was
      greater (P < .001) among subjects with mandibular prognathism. CONCLUSIONS: The
      hypothesis is rejected. Sagittal mandibular development had significant effects
      on the dimensions of the awake pharyngeal airway passage.

PMID- 20677956
TI  - Effects of extraction versus non-extraction treatment on oropharyngeal airway
      volume.
AB  - OBJECTIVE: To compare the effects of extraction vs nonextraction orthodontic
      treatments on oropharyngeal airway volume. MATERIALS AND METHODS: An existing
      patient database was screened for pretreatment (T0) and posttreatment (T1) cone
      beam computed tomography (CBCT) scans and complete medical histories. Twenty
      patients treated with removal of four premolars (ExtG) and 20 controls (NExtG),
      were matched for age, gender, ethnicity, height, weight, body mass index, and
      oropharyngeal (OP) volumes, among other variables. Constructed lateral
      cephalograms (three skeletal and four dental variables) and OP volumes were
      measured at T0 and T1 using Dolphin Imaging 11.0. Independent sample t-tests were
      used to compare the groups at T0 and the outcome variables at T1. Paired sample t
      tests were used to compare the mean changes from T0 to T1. Statistical
      significance was set at P < or = .05. RESULTS: Changes from T0 to T1 were found
      to be significant in both groups for CoA, CoGn, U1-FH, and IMPA. In the ExtG
      alone, U1-Na Perp and L1-Na Perp were also significantly different from T0 to T1.
      Despite the observed differences, no significant differences were found at the
      end of treatment between the mean OP volumes for either group (12,675.6 +/-
      4483.6 for ExtG; 12,002.7 +/- 2857.0 for NExtG, P > .05). Similarly, the mean
      changes in OP volume (1082.6 mm(3) and 1701.1 mm(3) for ExtG and NExtG,
      respectively) and increase in mean minimal constricted axial areas (17.4 mm(2)
      and 1.9 mm(2) for ExtG and NExtG, respectively, P > .05) from T0 to T1 were not
      significant for the two groups. CONCLUSION: Extraction of four premolars with
      retraction of incisors does not affect OP airway volume.

PMID- 20677957
TI  - Lower incisor inclination changes during Xbow treatment according to vertical
      facial type.
AB  - OBJECTIVE: To evaluate the magnitude of lower incisor inclination associated with
      the vertical facial type in adolescent Class II patients treated with the Xbow
      appliance. MATERIALS AND METHODS: A total of 172 consecutive Class II patients
      treated with only the Xbow appliance were used. The sample was divided into three
      groups based on their vertical facial type (24 short, 122 normal, and 25 long
      facial types). The mean age was 11.11 years at T1 with a mean active Xbow time of
      4.5 months. A mean of 6.4 months passed after the Xbow deactivation before T2
      radiograph. RESULTS: No significant association between lower incisor
      proclination and vertical facial type was found. Actual differences between T1
      and T2 did exist. In most cases, these differences may be considered clinically
      relevant, but when the large interindividual variability is considered, the
      differences between the groups could not be statistically supported. At T1, a
      distinct trend to have more proclined lower incisors in the short (100.5 degrees
      ) compared with the long (91.3 degrees ) facial types was found. During
      treatment, a trend was identified for more proclination of the lower incisor the
      shorter the face. CONCLUSIONS: Although lower incisors do procline with the use
      of the Xbow appliance, facial type does not appear to affect the amount of lower
      incisor inclination. The magnitude of the incisor proclination can be considered
      not clinically relevant, but a large individual variation in the incisor response
      was identified.

PMID- 20677958
TI  - Enamel surface roughness after debonding.
AB  - OBJECTIVE: To test the hypotheses that (1) there is no significant difference
      between the effects of two burs on the surface roughness of enamel after
      orthodontic debonding, and (2) there is no difference between resin removal times
      of the two burs. MATERIALS AND METHODS: The crowns of 20 premolars were embedded
      in acrylic blocks, and the buccal surfaces were subjected to atomic force
      microscopy (AFM), with measurement of initial roughness values. The brackets were
      bonded with a light-cured adhesive and were debonded with a debonding plier. In
      half of samples, adhesive remnants were removed with a tungsten carbide bur,
      whereas a fiber-reinforced composite bur was used in the other half. The second
      AFM measurements were made after resin removal. Duration of removal procedures
      was also recorded. Results of roughness and duration measurements were analyzed
      with the use of repeated measurements analysis of variance and independent t
      tests, respectively. RESULTS: The two resin removal instruments had significantly
      different effects on enamel roughness; higher average roughness (Sa) (P < .001),
      root mean square roughness (Sq) (P = .046), and maximum roughness depth (Smax) (P
      < .001) values were obtained with use of the tungsten carbide bur. Time required
      for resin removal with the composite bur was significantly greater than time
      required with the carbide bur (P < .001). CONCLUSION: The hypothesis is rejected.
      The composite bur used for resin removal creates smoother surfaces after
      orthodontic bonding; however, the process takes longer than it does when the
      tungsten carbide bur is used.

PMID- 20677959
TI  - Force and amount of resin composite paste used in direct and indirect bonding.
AB  - OBJECTIVE: To investigate the relationship between the forces applied by the
      operator and the amount of adhesive used in the direct and indirect bonding
      methods. MATERIALS AND METHODS: A system for measuring the force applied by
      operator was used to test specimens prepared by 12 orthodontic specialists. To
      determine the proper amount of adhesive, metal brackets were bonded to
      transparent resin teeth using composite resin paste and different forces (100,
      200, and 300 g); the area of the composite resin paste was then measured using
      image-analysis software. The mean forces applied in direct and indirect bonding
      were compared by Student's t-test. RESULTS: Various values for force were
      obtained for the direct bonding (53-940 g) and indirect bonding (150-870 g)
      techniques. Although in all cases the area of composite resin paste after the
      application of constant force was greater than the area of the metal brackets, an
      insufficient amount of composite resin paste on the bracket base was observed
      with forces of 100 and 200 g. CONCLUSIONS: A force of greater than 200 g might be
      preferable for obtaining a thin composite resin layer and for achieving
      sufficient spreading of the composite resin paste.

PMID- 20677960
TI  - Bracket bond strength comparison between new unfilled experimental self-etching
      primer adhesive and conventional filled adhesives.
AB  - OBJECTIVE: To determine if a new unfilled experimental self-etching primer (SEP)
      adhesive system (SBP-40TX + C&B Metabond) that incorporates a methyl methacrylate
      based 4-META/TBB (4-methacryloxyethyl trimellitate anhydride tri-n-butyl borane)
      resin can provide adequate shear bond strength (SBS) when used for bonding
      orthodontic brackets. METHODS AND MATERIALS: Forty-eight human maxillary
      premolars were randomly divided into three groups of 16 specimens each. Brackets
      were bonded with three bonding systems. A filled Bis-GMA/TEGDM (triethylene
      glycol dimethacrylate)-based SEP adhesive system (Transbond Plus) and an unfilled
      conventional etch-and-rinse adhesive system (C&B Metabond) were used for
      comparison. The SBS for each sample was examined with a universal testing
      machine, and the Adhesive Remnant Index score was calculated. Enamel surfaces
      after conditioning were examined using a scanning electron microscope. Data were
      compared by one-way analysis of variance and a chi(2) test. RESULTS: The
      experimental SEP showed a milder etching pattern than Transbond Plus SEP. No
      statistically significant differences in the mean SBS were found between the
      specimens bonded with the unfilled experimental SEP adhesive system (10.0 MPa)
      and the filled SEP adhesive system (8.7 MPa). The unfilled experimental SEP
      adhesive system showed less residual adhesive than the filled SEP adhesive
      system. CONCLUSIONS: The unfilled experimental SEP adhesive system showed a
      clinically sufficient SBS that was equivalent to the filled SEP adhesive system.

PMID- 20677961
TI  - Torsional superelasticity of NiTi archwires.
AB  - OBJECTIVE: To reproduce and compare the intraoral torsional behavior of 10
      commonly used preformed upper NiTi 0.017 x 0.025 archwires in 0.018-slot brackets
      at 20 degrees C, 35 degrees C, and 55 degrees C. MATERIALS AND METHODS: Ten upper
      preformed NiTi archwires were compared to a multibraided stainless steel wire. An
      original testing bench was used to reproduce palatal root torque applied onto an
      upper central incisor with a maximum value of 1540 g x mm. Ten samples of each
      wire type were tested at 20 degrees C, 35 degrees C, and 55 degrees C each.
      RESULTS: Loading and unloading at 20 degrees C revealed three categories of
      wires: a group of four NiTi wires of relative stiffness bereft of any
      superelasticity, a group of six NiTi wires displaying some horizontal plateau,
      and finally the stainless steel wire of lesser stiffness. Testing at the average
      oral temperature of 35 degrees C produced the same three categories of wires,
      with only 2 of 10 NiTi wires displaying a superelastic effect (Copper NiTi 35
      degrees C and 40 degrees C). None of the NiTi wires was superelastic at 55
      degrees C. Moments increased with temperature as the martensite was replaced by
      the more rigid austenite. CONCLUSION: This study showed that most NiTi wires did
      not exhibit in torsion the superelastic effect traditionally described in
      bending. The combination of straight-wire prescriptions and rectangular
      superelastic NiTi archwires did not provide optimal constant moments necessary to
      gain third-order control of tooth movement early in treatment. A braided
      stainless steel rectangular archwire displayed better torsional behavior at 35
      degrees C than most NiTi archwires of the same dimensions.

PMID- 20677962
TI  - Dimensional change over time of extended-storage alginate impression materials.
AB  - OBJECTIVES: To evaluate the dimensional change over time of two extended-storage
      alginate impression materials. METHODS: Impressions were made of stainless steel
      dies in accordance with ADA Specification No. 18 using three alginates: two
      extended-storage alginates and one conventional alginate. The impressions were
      stored for 30 minutes, 48 hours, or 100 hours (n = 10
      impressions/material/storage time). Following the respective storage times,
      dimensional change was measured by comparing the length of the middle horizontal
      line in the impression with the same line on the die and computing percent
      difference. RESULTS: Significant differences in dimensional change were noted
      between materials across time (P < .05). All materials exhibited shrinkage after
      30 minutes, with the conventional alginate continuing to shrink over time and the
      extended-storage alginates expanding with increased storage time. The
      conventional alginate was most accurate after 30 minutes. In contrast, one
      extended-storage alginate demonstrated minimal dimensional change at all storage
      times, and another was most accurate after 100-hour storage. CONCLUSIONS:
      Evidence suggests that delayed pouring with dental gypsum should not adversely
      affect dimensional accuracy of the generated casts with both extended-storage
      alginates. However, only one of the extended-storage materials appears suitable
      for both short-term and extended-storage applications.

PMID- 20677963
TI  - An orthodontic oral appliance.
AB  - OBJECTIVE: This pilot study was performed to test the hypothesis that an
      orthodontic oral appliance (OA) that is designed to work against the backwardly
      directed forces on the upper incisors may counteract the reduction in overjet
      from these devices. MATERIALS AND METHODS: Thirty patients with normal bites,
      good oral health, and milder sleep apnea were randomized to treatment with either
      OAs or orthodontic OAs. Bite changes were evaluated on plaster casts and
      radiographs and by questionnaires after a mean of 2.4 years in 19 frequent users.
      RESULTS: Four of nine patients in the orthodontic OA group increased their
      overjet by > or =0.4 mm, while none of the 10 patients in the OA group
      experienced that effect. CONCLUSION: Only the orthodontic OA increases the
      overjet; this design may therefore be beneficial to patients at risk of negative
      effects on their bite during OA treatment.

PMID- 20677964
TI  - Crown-root ratio of permanent teeth in cleft lip and palate patients.
AB  - OBJECTIVES: To determine root lengths of fully developed permanent teeth of cleft
      lip and palate (CLP) patients and to define their crown-root (C/R) ratios.
      METHOD: Crown height and root length of permanent teeth were measured from
      panoramic radiographs of 44 CLP patients and 37 controls. A total of 1397 teeth
      were measured, and C/R ratios were calculated. RESULTS: Higher C/R ratios were
      found in CLP patients; this was statistically significant for both maxillary and
      mandibular incisors and canines. Bilateral CLP subjects showed higher C/R ratios
      in general than unilateral CLP subjects. Roots of maxillary incisors, canines,
      and some other teeth were significantly shorter in CLP patients than in controls.
      CONCLUSIONS: CLP patients should be considered to have unfavorable C/R ratios,
      which could be the result of short root lengths for some teeth.

PMID- 20677965
TI  - Development of a sustained fluoride delivery system.
AB  - OBJECTIVE: To develop a novel delivery system by which fluoride incorporated into
      elastomeric rings, such as those used to ligate orthodontic wires, will be
      released in a controlled and constant manner. MATERIALS AND METHODS: Polyethylene
      co-vinyl acetate (PEVA) was used as the model elastomer. Samples (N = 3) were
      prepared by incorporating 0.02 to 0.4 g of sodium fluoride (NaF) into previously
      prepared PEVA solution. Another group of samples prepared in the same manner were
      additionally dip-coated in PEVA to create an overcoat. Fluoride release studies
      were conducted in vitro using an ion selective electrode over a period of 45
      days. The amount of fluoride released was compared to the optimal therapeutic
      dose of 0.7 microg F(-)/ring/d. RESULTS: Only coated samples with the highest
      fluoride content (group D, 0.4 g of NaF) were able to release fluoride at
      therapeutic levels. When fluoride release from coated and uncoated samples with
      the same amount of NaF were compared, it was shown that the dip-coating technique
      resulted in a fluoride release in a controlled manner while eliminating the
      initial burst effect. CONCLUSIONS: This novel fluoride delivery matrix provided
      fluoride release at a therapeutically effective rate and profile.

PMID- 20677966
TI  - Pulpal blood flow changes due to rapid maxillary expansion.
AB  - OBJECTIVE: To determine the pulpal blood flow (PBF) changes in anchorage teeth
      associated with the high forces of a rapid maxillary expansion (RME) appliance.
      MATERIALS AND METHODS: The study was performed with 14 girls and 7 boys for a
      total of 21 patients between 10 and 15 years of age (mean, 13.1 +/- 1.39 years).
      A modified acrylic bonded RME appliance was used as an expansion appliance. Laser
      Doppler flowmetry was used for the pulpal perfusion measurements. Records were
      taken from 42 upper central incisors, 28 canines, and 42 first molars at the
      following time intervals: just before expansion (T1); at the first week of
      expansion (T2); at the end of the expansion process (T3); and at the third (T4),
      seventh (T5), and 12th weeks of retention (T6). The data gained were
      statistically evaluated by parametric tests. RESULTS: PBF values of the anchorage
      teeth were doubled at the first week of expansion; however, these values began to
      decrease because of separation of the median palatal suture. PBF values tended to
      reach their initial values during the retention period. Pulpal perfusion changes
      of all examined anchorage teeth were similar to each other from the beginning to
      the end of the evaluation. CONCLUSION: PBF changes that occur with RME are
      reversible.

PMID- 20677967
TI  - The relationship between personality traits, pain perception and attitude toward
      orthodontic treatment.
AB  - OBJECTIVE: To investigate the relationship between personality traits and a
      person's attitude toward orthodontic treatment and perception of pain during
      orthodontic treatment. MATERIALS AND METHODS: The sample consisted of two groups:
      group 1 consisted of 200 untreated subjects (100 males, 100 females; average age,
      21.50 +/- 3.35 years), and group 2 consisted of 200 treated subjects (100 males,
      100 females; average age, 20.92 +/- 2.48 years). The instrument for data
      collection was a questionnaire that included assessment of patients' personality
      profiles, pain expectation for untreated subjects, pain experience for treated
      subjects, and attitudes toward orthodontic treatment. RESULTS: Gender, treatment
      status, and personality traits did not affect subjects' average attitude toward
      orthodontic treatment, whereas gender was the only variable that affected
      subjects' average pain perception (P < .01). The average attitude score in
      subjects who experienced pain during orthodontic treatment was 5.06 +/- 1.43,
      compared to 4.32 +/- 1.35 for subjects who did not experience pain (P < .001).
      The average pain perception scores in treated subjects with previous knowledge of
      orthodontic treatment was 5.29 +/- 1.94, compared to 6.07 +/- 1.95 in subjects
      who did not have previous knowledge of orthodontic treatment (P < .01).
      CONCLUSIONS: Personality traits did not affect attitude toward orthodontic
      treatment and pain perception/experience during orthodontic treatment. A more
      positive attitude was found in patients who experienced less pain during
      orthodontic treatment.

PMID- 20677968
TI  - Influence of gender on office staff management in orthodontics.
AB  - OBJECTIVE: To examine the gender differences in managing practice and staff
      members in orthodontic practices. MATERIALS AND METHODS: All orthodontists in
      Virginia and Maryland (n = 427) were surveyed and demographic information was
      collected. For the crude analyses of the data, a Fisher's exact test or chi(2)
      test was performed. For the adjusted analyses, genders were compared using a
      logistic regression or analysis of covariance. The covariates were adjusted for
      age, program length, years in practice, number of years since graduation, and
      practice state. RESULTS: The length of the residency program attended did not
      differ with gender. No gender differences in practice ownership or creating the
      practice were observed. There was a significant gender difference in
      implementation of performance reviews: female orthodontists were more likely to
      provide performance reviews and tended to accept more poor reviews before staff
      termination than male orthodontists. However, when provided, no gender difference
      was observed in the number of performance reviews. CONCLUSION: Gender has a
      significant impact on the implementation of performance reviews in practices.
      Practice ownership status was not influenced by providers' gender.

PMID- 20677969
TI  - Factors associated with long-term patient satisfaction.
AB  - OBJECTIVE: To identify factors associated with patient satisfaction at least 5
      years after orthodontic treatment. MATERIALS AND METHODS: A total of 209
      orthodontic patients were included in the study. All subjects were treated with
      upper and lower fixed orthodontic appliances. Dental casts (n = 627) were
      examined using the Peer Assessment Rating (PAR) Index pretreatment (T1), at the
      end of treatment (T2) and at a long-term follow-up (mean, 8.5 years; T3). At T3,
      a Dental Impact on Daily Living questionnaire was used to assess the long-term
      effects of orthodontic treatment on daily living and satisfaction with the
      dentition. Multiple regression analyses were used to quantify associations
      between patient satisfaction and changes produced by the orthodontic treatment
      (PAR T2-T1), posttreatment stability (PAR T3), age at the start of treatment
      (T1), treatment duration (T2-T1), gender, and extraction. RESULTS: Orthodontic
      treatment produced a significant improvement of 94.2% in the PAR Index (T2-T1),
      but this change was not associated with the level of satisfaction when the
      patient was questioned at least 5 years after treatment. Regression analysis
      showed that satisfaction was significantly associated only with the long-term
      posttreatment PAR index (r(2) = 0.125, P < .0001). No significant association was
      observed with the severity of malocclusion at the beginning (PAR-T1) or end of
      the orthodontic treatment (PAR-T2), age at T1, the amount of time taken during
      orthodontic treatment, gender, or extraction. CONCLUSIONS: Over the long term,
      patient satisfaction is slightly associated with the stability of the orthodontic
      treatment regardless of the initial occlusal condition or the final result of the
      orthodontic treatment.

PMID- 20677970
TI  - Influence of lower facial height changes on frontal facial attractiveness and
      perception of treatment need by lay people.
AB  - OBJECTIVE: To test the hypothesis that lower facial height has no influence on
      frontal facial attractiveness and treatment need perception of lay people.
      MATERIALS AND METHODS: Frontal facial silhouettes of a man and a woman with
      normal lower facial height values (male: 81.5 mm; female: 70.5 mm) were modified
      by increasing and decreasing their lower facial heights in steps of 1 mm to
      obtain frontal images with different lower facial height alterations ranging from
      +6 mm to -6 mm for each sex. A panel of 100 lay people scored each silhouette's
      attractiveness on a 100-mm visual analogue scale (VAS) and also indicated whether
      they would seek treatment if the image represented their own. The Wilcoxon signed
      rank test was used to compare the VAS scores. RESULTS: Unaltered +/-1-mm and +/-2
      mm silhouettes got the highest VAS scores. Scores were significantly lower (P <
      or = .001) as the divergence from the normal value exceeded 2 mm. Beyond +3 mm
      and -4 mm in females and +4 mm and -3 mm in males the difference between the
      scores became statistically insignificant. At +/-4 mm, more than 75% of the
      raters elected to have treatment. CONCLUSION: The hypothesis was rejected.

PMID- 20677971
TI  - Maxillary advancement using distraction osteogenesis with intraoral device.
AB  - This article describes the surgical orthodontic treatment of maxillary hypoplasia
      in a patient with cleft lip and palate using maxillary distraction osteogenesis
      with internal maxillary distractors. Maxillary advancement was performed to
      correct the retrusive maxillary facial profile and Class III malocclusion.
      Rotational movement of the distraction segment was made to correct the upper
      dental midline. Although maxillary advancement was insufficient because of
      unexpected breakage of the intraoral distractor after completion of the
      distraction, skeletal traction with a face mask compensated for the shortage.
      Successful esthetic improvement and posttreatment occlusal stability were
      achieved with no discernible relapse after 2 years of retention.

PMID- 20677972
TI  - Skeletal Class III and open bite treated with bilateral sagittal split osteotomy
      and molar intrusion using titanium screws.
AB  - Two-jaw surgery has been performed for the treatment of severe skeletal open bite
      cases to obtain stability of occlusion after treatment. If molar intrusion with
      titanium screws could be performed instead of surgical superior repositioning of
      the maxilla, the incidence of surgical invasion would be reduced. However, there
      have been few reports of such a therapy. This case report describes treatment for
      skeletal Class III and open bite with bilateral sagittal split osteotomy and
      intrusion of the molars using titanium screws. The patient had a concave profile,
      a long lower facial height, Class III malocclusion, and excessive anterior open
      bite following mandibular protrusion and a high mandibular plane angle. The
      mandible autorotated closed 3.5 degrees following intrusion of the upper and
      lower molars using titanium screws during the presurgical orthodontic treatment
      phase. After the autorotation of the mandible, a mandibular setback with a
      bilateral sagittal split osteotomy was performed. The posttreatment records
      showed a good facial profile and occlusion. The mandible was stable 1 year after
      surgery. These results demonstrate that surgical orthodontic treatment combined
      with bilateral sagittal split osteotomy and intrusion of the molars using
      titanium screws can reduce the need for surgical invasion by avoidance of
      maxillary surgery and was effective for correcting the facial profile and
      occlusion in a skeletal Class III and open bite patient.

PMID- 20677973
TI  - Epidemiological patterns and hospital characteristics associated with increased
      incidence of Clostridium difficile infection in Quebec, Canada, 1998-2006.
AB  - OBJECTIVE: To explore epidemiological patterns of the incidence of Clostridium
      difficile infection (CDI) and hospital characteristics associated with increased
      incidence during nonepidemic and epidemic years. DESIGN: Retrospective and
      prospective ecological study. SETTING: Eighty-three acute care hospitals
      participating in CDI surveillance in the province of Quebec, Canada. METHODS: A
      Serfling-type regression model applied to data obtained from an administrative
      database (1998-2006) and prospective Quebec CDI surveillance (2004-2006) was used
      to calculate expected CDI baseline incidence and to detect incidence exceeding
      the defined epidemic threshold at the provincial and hospital level.
      Multivariable Poisson regression was used to determine hospital characteristics
      associated with increased incidence during nonepidemic (1998-2001) and epidemic
      (2003-2005) periods. RESULTS: During the study period (1998-2006), 4,525,847
      discharges, including 45,508 with a CDI in any diagnosis field, were reported by
      83 hospitals. During 1998-2001, the average Quebec incidence of CDI was 10,304
      cases in 1,775,822 discharges (5.8 cases per 1,000 discharges) and presented a
      pattern of seasonality, with similar patterns at the hospital level for some
      hospitals. The Quebec epidemic started in October-November 2002 and peaked in
      March 2004 at 845 cases in 40,852 discharges (20.7 cases per 1,000 discharges).
      In multivariable analysis, higher incidence was associated with location in
      Montreal and surrounding regions, greater hospital size, larger proportion of
      hospitalized elderly patients, longer length of stay, and greater proportion of
      comorbidities in patients, whereas teaching profile was associated with decreased
      incidence during both nonepidemic and epidemic periods. The effect of
      geographical location on incidence was greater during the epidemic. CONCLUSION:
      Baseline incidence from nonepidemic years and hospital characteristics associated
      with CDI incidence should be taken into account when estimating the efficacy of
      interventions.

PMID- 20677974
TI  - Positive deviance and hand hygiene: more questions than answers.

PMID- 20677976
TI  - Hand hygiene product volume measurement: an integral part of a multiple-method
      program.

PMID- 20677978
TI  - An integrated clinical microbiology service ensures optimal early empirical
      antimicrobial therapy for methicillin-resistant Staphylococcus aureus bloodstream
      infection.

PMID- 20677980
TI  - Inside-out: the changing epidemiology of methicillin-resistant Staphylococcus
      aureus.

PMID- 20677981
TI  - Transcriptome analysis of alkali shock and alkali adaptation in Listeria
      monocytogenes 10403S.
AB  - Alkali stress is an important means of inactivating undesirable pathogens in a
      wide range of situations. Unfortunately, Listeria monocytogenes can launch an
      alkaline tolerance response, significantly increasing persistence of the pathogen
      in such environments. This study compared transcriptome patterns of alkali and
      non-alkali-stressed L. monocytogenes 10403S cells, to elucidate the mechanisms by
      which Listeria adapts and/or grows during short- or long-term alkali stress.
      Transcription profiles associated with alkali shock (AS) were obtained by DNA
      microarray analysis of midexponential cells suspended in pH 9 media for 15, 30,
      or 60 min. Transcription profiles associated with alkali adaptation (AA) were
      obtained similarly from cells grown to midexponential phase at pH 9. Comparison
      of AS and AA transcription profiles with control cell profiles identified a high
      number of differentially regulated open-reading frames in all tested conditions.
      Rapid (15 min) changes in expression included upregulation of genes encoding for
      multiple metabolic pathways (including those associated with Na+/H+ antiporters),
      ATP-binding cassette transporters of functional compatible solutes, motility, and
      virulence-associated genes as well as the sigma(B) controlled stress resistance
      network. Slower (30 min and more) responses to AS and adaptation during growth in
      alkaline conditions (AA) involved a different pattern of changes in mRNA
      concentrations, and genes involved in proton export.

PMID- 20677982
TI  - Perceived safety and teen risk taking in online chat sites.
AB  - Framed by theories of adolescent development, this study explored relationships
      among adolescents' perceptions of chat-site safety, time spent chatting, and
      risky online behaviors. Tenth graders (N = 139) in rural Midwestern U.S. schools
      completed surveys. Factor analysis produced three factors each for perception of
      safety and risk-taking behaviors. Regression analyses revealed that perception of
      safety factors were useful in predicting online risk-taking behaviors. Teens with
      more social discomfort and those who thought it was safe to reveal personal
      information and trust chat-site "friends" were more likely to take risks. As time
      spent in chat sites increased, so did risk-taking behaviors. Implications for
      educators and parents are discussed, such as initiation of conversations about
      safe Internet use, parental participation in chat sites as teens' invited
      "friends," and school programs to teach safe online practices.

PMID- 20677983
TI  - Internet use and self-injurious behaviors among adolescents and young adults: an
      interdisciplinary literature review and implications for health professionals.
AB  - The ease and accessibility of the Internet has created an environment where
      individuals can both remain anonymous and interact with others who share their
      interests. Electronic discussion boards and social-networking sites allow
      individuals to communicate with others, via public postings, regarding specific
      topics of interest. These interactions have taken a therapeutic form for
      adolescents and young adults seeking practical and emotional support on the
      Internet. Support sites exist for many issues and illnesses, but sites focusing
      on self-injurious behaviors (SIB) have garnered recent attention because of their
      potential to either aid in recovery or exacerbate symptoms. SIB are those
      behaviors in which an individual purposely inflicts harm to his or her body.
      Based on an interdisciplinary literature review, self-injurious Web sites have
      been shown to provide anonymous support for individuals experiencing SIB from
      others who have experienced similar emotions. However, the literature also
      reveals that some peers who are providing the support are accepting of SIB and
      guilty of glossing over potentially serious posts. The emotional support received
      on these sites differs from services those individuals would receive from
      professionals, such as coping strategies to deal with stressors and a more
      detailed examination of ominous signs. The use of these Web sites as a help or a
      hindrance to an individual's recovery from SIB remains highly contested; health
      professionals should be aware of the pros and cons associated with this
      phenomenon and should be able to identify safe means of communication for clients
      suffering from SIB.

PMID- 20677984
TI  - The relation of Internet use to prosocial and antisocial behavior in Chinese
      adolescents.
AB  - Prosocial and antisocial Internet use is investigated in this study by
      constructing an objective measure called the Adolescent Internet Use
      Questionnaire (AIUQ). The sample consists of 509 secondary school students in
      Hong Kong. Based on the previous review of the literature, the present study
      tests the following two hypotheses: (a) sex difference hypothesis: boys are more
      delinquent in Internet use than are girls; (b) positive association hypothesis:
      there is a positive association between Internet behavior and daily social
      behavior. In other words, positive Internet behavior is positively associated
      with positive daily social behavior, and negative Internet behavior is positively
      associated with negative daily social behavior. In general, the two hypotheses
      are supported by the data in this study. The internal consistency reliability and
      predictive validity of the major indices of the AIUQ are also substantiated by
      the present data.

PMID- 20677985
TI  - Advances in aptamers.
AB  - Aptamers are nucleic acid sequences synthesized through in vitro selection and
      amplification technique, possessing a broader range of applications in
      therapeutics, biosensing, diagnostics, and research. Aptamers offer a number of
      advantages over their antibodies counterpart, one of them is their ability to
      undergo chemical derivatization to increase their life in the body fluids and
      bioavailability in animals. Although aptamers were discovered in 1990s, they have
      become one of the most widely investigated molecules, with a huge number of
      publications in the last decade. This article presents an overview of the
      advancements that have been made in aptamers. We mainly focused on articles
      published since 2005.

PMID- 20677986
TI  - Safety and efficacy of a superior caliceal puncture in pediatric percutaneous
      nephrolithotomy.
AB  - BACKGROUND AND PURPOSE: Access through the superior calix for percutaneous
      nephrolithotomy (PCNL) often breaches the diaphragm and is believed to have
      greater complications than access through other calices. We evaluated the safety
      and efficacy of a superior caliceal access in pediatric patients who were
      undergoing PCNL. PATIENTS AND METHODS: Operative and recovery data for pediatric
      patients (up to 16 years old) who were undergoing PCNL for renal calculi were
      prospectively entered into a database and reviewed. Patients with a superior
      calix puncture were compared with those in whom the superior calix was not
      punctured. Stone clearance was assessed by intraoperative fluoroscopy and
      postoperative radiography in all patients and ultrasonography and CT scan in
      selected cases. RESULTS: Over a 2-year period, 26 pediatric patients (mean age
      11.12 years; range 4-16 years) underwent 27 PCNLs. Stone bulk ranged from 200 to
      1150 mm2 (mean 656.03 mm2). Nine patients had staghorn stones. Thirteen patients
      (14 renal units) had primary superior calix access with 13 of these being
      supracostal (above the 12th rib). Four of these had staghorn calculus. All stones
      were fragmented using a pneumatic lithoclast. Second-look PCNL was necessary in
      two patients. Complete clearance was achieved in all except one patient in each
      group with superior and nonsuperior caliceal puncture. Hydrothorax developed in
      one patient with supracostal puncture necessitating tube drainage while abdominal
      collection developed in one in patient who underwent the nonsuperior calix
      approach. Both patients recovered with no sequelae. CONCLUSIONS: The superior
      calix puncture is safe and effective in the pediatric population.

PMID- 20677987
TI  - A novel bulldog clamp technique for management of a distal ureter and bladder
      cuff during laparoscopic nephroureterectomy.
AB  - A novel technique for achieving complete laparoscopic excision of the intramural
      ureter with a bladder cuff is presented using the bulldog clamp without opening
      the urinary tract.

PMID- 20677988
TI  - Factors that predict spontaneous passage of a small distal ureteral stone <5 mm.
AB  - PURPOSE: We assessed the role of the unenhanced helical computed tomography
      (UHCT) for prediction of concurrent ureteral lesions associated with small
      impacted stones presenting in distal ureter. MATERIALS AND METHODS: From May 2004
      to June 2009, we evaluated 30 cases with impacted distal ureteral stones <5 mm.
      All of the patients were evaluated with unenhancing UHCT, and the secondary signs
      on UHCT were graded on a scale of 0 to 3. All of the patients were treated by
      ureteroscopic pneumatic lithotripsy. Ureteral lesions associated with impacted
      stones were characterized on the basis of the ureteroscopic findings. RESULTS:
      Ureteroscopic procedures showed that impacted distal ureteral stones <5 mm had
      concurrent ureteral lesions such as severe mucosal edema, strictures, ureteral
      polyps, or submucosal stones. Long-term stone impaction and the UHCT findings of
      a higher degree of the tissue rim sign, hydronephrosis, and perinephric fat
      stranding were associated with a higher likelihood of the presence of underlying
      ureteral lesions. CONCLUSIONS: The secondary signs on UHCT such as high degree of
      tissue rim sign, hydronephrosis, and perinephric fat stranding seem to be useful
      signs in predicting the presence of concurrent ureteral lesions. In those cases,
      early intervention might have better outcomes than conservative therapy.

PMID- 20677989
TI  - Comparative analysis of outcome between open and robotic surgical repair of
      recurrent supra-trigonal vesico-vaginal fistula.
AB  - INTRODUCTION: Recurrence of fistula is one of the very common complications of
      fistula repair. The disease has immense psychosomatic effect on the patients due
      to continuous leakage of urine. Management of recurrent vesico-vaginal fistula
      (VVF) repair poses a challenge to surgeons. MATERIALS AND METHODS: Group I-12
      patients with recurrent VVF, having robotic repair from August 2006 to June 2008,
      were included in the present study. Group II-20 patients matched in all possible
      parameters with recurrent VVF having open surgical repair in the past were taken
      as controls. Patients in both the groups were evaluated by assessing relevant
      clinical details; performing urine routine examination and culture, renal
      function test, three swab test, ultrasonogram-kidney, ureter, and bladder
      radiograph, intravenous urogram (to look for upper tract and rule out uretero
      vaginal fistula), and urethro-cystoscopy. The details were retrospectively
      recorded from the case sheets. RESULTS: In group I, 100% were successfully
      managed as compared with 90% in group II, but it was not statistically
      significant (p > 0.05). Mean blood loss was significantly less (p < 0.05) in
      group I compared with group II (mean 88 vs. 170 mL). The mean hospital stay also
      was significantly less (p < 0.05) in group I in comparison with group II (mean
      3.1 vs. 5.6 days). None of the patients had complications in group I compared
      with group II, but it was not significant. CONCLUSION: The present study suggests
      that robotic VVF repair is a better option for recurrent fistulas in view of its
      reduced morbidity, without compromising the results.

PMID- 20677990
TI  - Acoustic access to the prostate for extracorporeal ultrasound ablation.
AB  - This study aimed to measure acoustic access to the prostate for extracorporeal
      ultrasound ablation. Both transabdominal and transperineal approaches were
      considered. The objective was to measure the size and shape of the aperture
      available for unobstructed targeting of the prostate. CT images of 17 randomly
      selected men > 56 years of age were used to create 3D reconstructions of the
      lower abdomen and pelvis. Rays were traced from target locations in the prostate
      toward the perineum and the abdomen. The maximum CT density encountered along
      each path was recorded; those paths that traversed structures with CT density
      exceeding a soft tissue threshold were considered to be blocked by bone.
      Unblocked rays comprised the accessible aperture. The aperture through the
      perineum was found to be a triangular-shaped region bounded by the lower bones of
      the pelvis varying significantly in size between subjects. The free aperture
      through the abdomen was wedge shaped limited by the pubis and also with great
      subject-to-subject variability. Average unblocked fractions of an f/1 transducer
      to target base, middle, and apex of the prostate along the urethra from the
      perineum were 77.0%, 94.4%, and 99.6%, respectively. Averages targeting from the
      abdomen were 86.1%, 52.3%, and 11.0%. Acoustic access to the prostate for therapy
      through the perineum was judged to be feasible. Access from the abdomen was
      judged to be sufficient for the base of the prostate, but likely inadequate for
      the middle and apex.

PMID- 20677991
TI  - The twister fiber: a comparative study of tissue interaction between this novel
      fiber and the side-firing fiber using the 980 nm laser in bovine kidneys.
AB  - Twister fiber has been recently introduced to convey the 980 nm laser. It is an
      end-firing fiber with terminal angulation. Theoretically, this fiber has many
      advantages over the standard side-firing fiber. Tissue characterization for such
      fiber has not been performed until now. It is important to carry out such a task
      to better understand the performance of this type of laser using this new fiber.
      Ablation capacity, fiber degradation, and maximum coagulation depth were tested
      for both the side-firing and the Twister fibers using a 980 nm diode laser system
      with a maximum output of 300 watts (Ceralas 300 system). The fibers have been
      tested on bovine kidneys. Laser powers used were 50, 100, 150, and 200 watts. The
      application time was 3 minutes for each experiment. Each experiment was repeated
      six times. Ablation rate was directly proportional to laser power reaching 2.4 +/
      0.24 g/minute for the side-firing fiber and 1.83 +/- 0.23 g/minute for the
      Twister fiber when the 200 watts power was reached. There was no statistical
      significant difference between the two fibers except at the 200 watts power. The
      side-firing fiber seems to resist degradation better at high power. The maximum
      coagulation depth was equivalent and did not significantly increase with power
      increase beyond the 100 watts. At 50 watts, the coagulation depth was
      significantly lower in the side-firing fiber. Both fibers produced significantly
      smaller coagulation at the 50 watts power setting compared with higher powers. In
      conclusion, both fibers performed well with regard to the ablation rate and
      produced a reasonable coagulation zone beyond the ablation area. The side-firing
      fiber seems to resist degradation more than the Twister fiber.

PMID- 20677992
TI  - Diagnostic utility and clinical value of postpercutaneous nephrolithotomy
      nephrostogram.
AB  - BACKGROUND AND PURPOSE: After percutaneous nephrolithotomy (PCNL), the current
      standard of care is to obtain a nephrostogram before removal of the nephrostomy
      tube to rule out distal ureteral obstruction. The aim of this study was to
      determine whether nephrostogram findings predict prolonged urinary drainage and
      postoperative ureteral stent insertion. PATIENTS AND METHODS: Data for all
      patients who had nephrostomy tubes inserted post-PCNL between January and
      December 2006 were retrospectively reviewed. Patients with radiolucent stones,
      concomitant procedures, or caliceal diverticula were excluded. All nephrostograms
      were reviewed to identify distal ureteral obstruction without evidence of
      residual fragments. The Fisher's exact test was used. RESULTS: Fifty patients who
      underwent 51 PCNLs were included in the study (one patient had bilateral PCNLs).
      Nephrostograms were performed on median postoperative day (POD) 2 (range POD 2
      8), and tubes were removed on median POD 2 (range POD 2-10). In 14 (27%) patients
      who had distal ureteral obstruction without ureteral stones, the nephrostomy tube
      was removed on the same day of nephrostography. Eight (16%) patients experienced
      a prolonged urinary leak (>24 hours). While obstruction on the nephrostogram
      predicted prolonged urinary leak (36% vs 8%; P = 0.02), none of these obstructed
      patients needed postoperative ureteral stent placement. A patient with a
      horseshoe kidney without distal ureteral obstruction had his nephrostomy removed
      on POD 2. He presented on POD 7 with prolonged urinary leakage and needed
      readmission with ureteral stent placement and Foley catheterization. CONCLUSION:
      While distal obstruction seems to predict prolonged urinary leakage (more than 24
      hours), it may not necessitate ureteral stent placement or prolonged nephrostomy
      drainage because blood clot or ureterovesical junction edema resolve
      spontaneously with expectant management.

PMID- 20677993
TI  - Impact of virtual reality-simulated training on urology residents' performance of
      transurethral resection of the prostate.
AB  - PURPOSE: There are virtual reality simulators for practicing the transurethral
      resection of prostate (TURP) procedure, but only few data on its effect on
      surgical performance are available. The purpose of this study was to test if
      practicing the TURP procedure in a virtual reality simulator (PelvicVision)
      increases the skills and dexterity of urology residents when performing the
      procedure on patients. MATERIALS AND METHODS: Twenty-four urology residents
      attended a 5-day course on diagnosis and treatment of benign prostatic
      enlargement. Each of the residents performed three video-recorded TURP
      procedures. Between two of the procedures (on day 2 and 3, or 3 and 4) the
      residents underwent criterion-based practice using a simulator. The TURP
      procedure was evaluated using objective structured assessment of technical
      skills. Video-recordings of the procedures were analyzed on a minute-to-minute
      basis. RESULTS: Mean practice time in the simulator was 198 minutes before
      reaching the criterion level. Comparison of the first and last TURP procedures
      showed an increase in autonomous operation time and time spent on resection, and
      a tendency to decreased hemostasis time without increased blood loss. The
      proportion of residents believed to be able to perform a simple TURP procedure
      increased from 10% to about 75%. Objective structured assessment of technical
      skills scores and self-evaluations were significantly improved. The scores
      increased significantly more with than without simulator practice. The resident's
      self-evaluations showed increased knowledge about the procedure and the technical
      equipment used. Patient follow-up showed no increased risks. CONCLUSIONS:
      Practice in a simulator-based environment improves the skills and dexterity of
      urology residents when performing the procedure on patients, without increased
      risks for the patients.

PMID- 20677994
TI  - Toward optimal health: the maternal benefits of breastfeeding.

PMID- 20677995
TI  - Sexual dysfunction, depression, and anxiety among patients of an inner-city
      menopause clinic.
AB  - OBJECTIVE: The objective of this study was to identify the prevalence of female
      sexual dysfunction (FSD) in a sample comprising women of mostly Hispanic descent
      and low socioeconomic status (SES). METHODS: Demographic data and symptoms
      related to sexuality were analyzed from 102 women who consecutively came to the
      Women's Life Center at Hartford Hospital (2004-2008). FSD was defined as
      decreased sexual desire, dyspareunia, or vaginal dryness; depression as one
      positive response to a validated three-question screening instrument; and anxiety
      as a positive response to whether the patient experiences anxiety sometimes or
      often. RESULTS: The cohort was 52.9 +/- 6.8 years of age (mean +/- standard
      deviation [SD]) and 80.0% Hispanic, and 47.8% were unemployed. The majority
      (92.8%) earned < $25,000, and most (95.8%) did not have a college degree. The
      prevalence of FSD was 75.6%. The prevalence of depression was 80.9% vs. 52.8% (p
      = 0.01) and that of anxiety was 76.6% vs. 45.7% (p = 0.01) among women with vs.
      without a decrease in sexual desire. The prevalence of depression was 83.3% vs.
      55.9% (p = 0.03) and that of anxiety was 76.7% vs. 52.9% (p = 0.07) among women
      who reported dyspareunia vs. those who did not. Problems sleeping was the only
      variable associated with a statistically higher likelihood of FSD (odds ratio
      [OR] 5.57, 95% confidence interval [CI] 1.22-25.33, p = 0.03). No significant
      differences were seen when comparing FSD between Hispanics and non-Hispanics.
      CONCLUSIONS: This sample of predominantly Hispanic women of low SES had a high
      prevalence of FSD. These data also suggest that poor sleep is significantly
      associated with FSD and that women of low SES with FSD may have a significantly
      higher prevalence of depression and anxiety.

PMID- 20677996
TI  - Hypothyroidism and intermediate metabolism: a complex relationship.

PMID- 20677997
TI  - The association between thyroid carcinoma and Hashimoto's thyroiditis: the
      ultrasonographic and histopathologic characteristics of malignant nodules.
AB  - BACKGROUND: Some but not all reports, particularly those of a retrospective
      nature, have noted an increased risk of carcinoma in thyroid nodules in patients
      with Hashimoto's thyroiditis (HT). Thyroid cancer (TC) in patients with HT,
      however, have been reported to have a better prognosis. In the presence of HT,
      the ultrasonography (US) appearance of the thyroid gland might vary greatly,
      making it more difficult to differentiate between benign and malignant nodules.
      The aim of this study was to determine if there is an association between TC and
      HT and to determine if the US and histopathologic characteristics of malignant
      nodules in patients with and without HT are similar. METHODS: Six hundred
      thirteen patients who underwent total thyroidectomy between 2005 and 2008 for
      nodular goiter were included in this study. The preoperative US characteristics
      and postoperative histopathologic features in patients with and without HT were
      compared. The diagnosis of HT was based on histopathologic features. RESULTS:
      Ninety-two patients had HT. The prevalence of TC in the HT patients was 45.7%. In
      contrast, it was 29% in patients without HT (p = 0.001). The prevalence of HT in
      the patients with TC was 21.8% and in patients without TC was 11.9% (p = 0.001).
      The rate of incidental TC, defined as TC identified during surgery or following
      histopathologic examination of permanent sections despite preoperative benign
      cytology results, was higher in patients with HT (33.3%) than in those without
      (13.0%) HT (p = 0.004). The US characteristics of papillary thyroid carcinoma,
      which included number of nodules, echogenity, echoic texture,
      microcalcifications, macrocalcifications, halo sign, and regularity of margins,
      were similar in the group with HT compared with the group without HT. When the
      histopathologic characteristics of papillary thyroid carcinoma in patients with
      and without HT were compared, again there was no significant difference.
      CONCLUSIONS: We suggest that there is an association between HT and TC, and HT
      may predispose to the development of TC. This indicates the need for close
      observation of neoplastic changes in patients with HT. Nevertheless, the presence
      of HT seems to have no effect on the US and histopathologic characteristics of
      malignant nodules in TC patients. This finding may indicate that evaluation of
      nodules and initial treatment of TC in these patients does not require different
      management.

PMID- 20677998
TI  - Markedly elevated serum calcitonin concentrations associated with initial
      presentation but not the recurrent presentation of medullary thyroid carcinoma.

PMID- 20677999
TI  - Is screening appropriate for occult cervical lymph node metastases in patients
      with well-differentiated thyroid cancer?

PMID- 20678001
TI  - Effect of SSRI antidepressants on L-thyroxine requirements.

PMID- 20678006
TI  - Neighborhood contextual factors, maternal smoking, and birth outcomes: multilevel
      analysis of the South Carolina PRAMS survey, 2000-2003.
AB  - BACKGROUND: Previous studies investigating relationships among neighborhood
      contexts, maternal smoking behaviors, and birth outcomes (low birth weight [LBW]
      or preterm births) have produced mixed results. METHODS: We evaluated independent
      effects of neighborhood contexts on maternal smoking behaviors and risks of LBW
      or preterm birth outcomes among mothers participating in the South Carolina
      Pregnancy Risk Assessment and Monitoring System (PRAMS) survey, 2000-2003. The
      PRAMS data were geocoded to 2000 U.S. Census data to create a multilevel data
      structure. We used a multilevel regression analysis (SAS PROC GLIMMIX) to
      estimate odds ratios (OR) and corresponding 95% confidence intervals (CI).
      RESULTS: In multivariable logistic regression models, high poverty, predominantly
      African American neighborhoods, upper quartiles of low education, and second
      quartile of neighborhood household crowding were significantly associated with
      LBW. However, only mothers resident in predominantly African American Census
      tract areas were statistically significantly at an increased risk of delivering
      preterm (OR 2.2, 95% CI 1.29-3.78). In addition, mothers resident in medium
      poverty neighborhoods remained modestly associated with smoking after adjustment
      for maternal-level covariates. The results also indicated that maternal smoking
      has more consistent effects on LBW than preterm births, particularly for mothers
      living in deprived neighborhoods. CONCLUSIONS: Interventions seeking to improve
      maternal and child health by reducing smoking during pregnancy need to engage
      specific community factors that encourage maternal quitting behaviors and reduce
      smoking relapse rates. Inclusion of maternal-level covariates in neighborhood
      models without careful consideration of the causal pathway might produce
      misleading interpretation of the results.

PMID- 20678007
TI  - Topological properties of the drug targets regulated by microRNA in human protein
      protein interaction network.
AB  - The investigation of topological properties of proteins in protein-protein
      interaction network (PPIN) has great potentials to identify basic protein
      functions and mechanisms of action. Based on human PPIN, previous study has shown
      that the topological properties of drug targets are significantly distinguished
      from those of proteins that are not targeted by drugs (non-drug-targets).
      MicroRNAs (miRNAs) are known to regulate gene expression at the post
      transcriptional level. To determine whether the differences in topological
      properties between drug targets and non-drug-targets are dominated by the
      proteins that are regulated by miRNA, we divided the drug targets into two sets:
      those are regulated by miRNA (mir-drug-targets) and those are not regulated by
      miRNA (non-mir-drug-targets). We compared the probability of interactions and
      five topological properties among the three types of proteins in human PPIN. Our
      results demonstrated that mir-drug-targets preferentially interact with other mir
      drug-targets and tend to be hub-bottlenecks. However, there was no bias on
      topological properties between non-mir-drug-targets and non-drug-targets. The
      same topological features are observed among non-drug targets. These findings
      indicate that miRNA regulation has an important role in human PPIN, and may be
      useful in the development of novel drugs.

PMID- 20678008
TI  - Biological evaluation of avidin-based tumor pretargeting with DOTA-Triazole
      Biotin constructed via versatile Cu(I) catalyzed click chemistry.
AB  - BACKGROUND: The biotin-avidin interaction remains a gold standard for the two
      step pretargeting approach to image tumor sites. We aim to develop two-step
      pretargeting systems utilizing (99m)Tc labeled biotin functionalized macrocyclic
      chelating agents synthesized using the highly efficient Cu(I) catalyzed azide
      alkyne cycloaddition for potential radioimaging applications. METHODS: A facile
      synthesis of DOTA-Triazole-Biotin, radiocomplexation with (99m)Tc and the
      pretargeting protocol is described. The synthesis features Cu(I) catalyzed click
      conjugation between biotinylated azide and propynyl functionalized DO3A. (99m)Tc
      radiolabeling was performed to detect the accumulation of avidin as the
      pretargeting agent. Cytotoxicity was determined using the trypan blue exclusion
      assay, macrocolony, and MTT assay. Cell uptake studies were performed using
      radiolabeled DOTA-Triazole-Biotin and compared with avidin treated cells for 2 h.
      Tumor imaging was performed in U-87MG cell line implanted tumor bearing nude mice
      and uptake of the radiotracer was estimated. RESULTS: All compounds have been
      successfully characterized by NMR and MS spectroscopy. More than 96%
      radiolabeling efficiency was obtained and the radioconjugate exhibited sufficient
      stability under physiological conditions. CONCLUSION: To summarize, a new
      candidate for avidin based two-step pretargeting of tumors has been synthesized
      and evaluated for potential imaging and diagnostic applications. The chelate
      possesses high stability under physiological conditions, exhibits effective
      interaction with its avidin target, and low nonspecific retention in vivo.

PMID- 20678009
TI  - Conjugates of daidzein-alliinase as a targeted pro-drug enzyme system against
      ovarian carcinoma.
AB  - Human ovarian cancer cells specifically bind the isoflavone daidzein. A chemical
      conjugate between daidzein and the garlic enzyme alliinase was prepared. The
      conjugate specifically bound to ovarian cancer cells and upon addition of the
      prodrug alliin, it effectively produced cytotoxic allicin molecules which killed
      the cancer cells. In vivo targeting and antitumor effect was confirmed by NIR and
      bioluminescence imaging using daidzein-alliinase-CyTE-777 conjugates and
      luciferase-expressing ovarian cancer cells. Co-localization of the fluorescent
      conjugate with bioluminescence was observed for intraperitoneal tumors while
      nonconjugated alliinase did not accumulate. Biodistribution studies with Europium
      labeled conjugate revealed a five fold higher uptake in tumors as compared to
      other tissues. Treatment of tumor bearing mice with daidzein-alliinase and alliin
      effectively attenuated tumor progression during the first 12 days while a 5-fold
      increase in bioluminescence was detected in placebo-treated animals. Autopsy
      revealed only small individual foci of luminescence at the site of tumor cells
      inoculation. Histological examination of organs and tissues did not reveal any
      additional foci of carcinoma or signs of toxicity. These results suggest that the
      targeted alliinase conjugates in the presence of alliin, generated
      therapeutically effective levels of allicin which were capable of suppressing
      tumor progression of intraperitoneal ovarian cancer in an animal model.

PMID- 20678010
TI  - Comparing the effectiveness of endoscopic full-thickness plication and endoscopic
      radiofrequency treatments for patients with GERD.

PMID- 20678012
TI  - Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer.
AB  - Evaluation of: Valle J, Wasan H, Palmer DH et al. Cisplatin plus gemcitabine
      versus gemcitabine for biliary tract cancer. N. Engl. J. Med. 362, 1273-1281
      (2010). Biliary tract cancer is a rare disease and it is associated with a poor
      clinical outcome and survival. A standard therapy has not been established yet.
      The evaluated article reports on the first Phase III randomized controlled
      multicenter trial (ABC-02 trial) on palliative chemotherapy for biliary tract
      cancer. A total of 410 patients with locally advanced or metastatic
      cholangiocarcinoma, gallbladder cancer or ampullary cancer were included to
      receive either cisplatin followed by gemcitabine or gemcitabine alone for up to
      24 weeks. The primary end point was overall survival and the secondary end point
      was progression-free survival. The median overall survival was 11.7 months in the
      cisplatin plus gemcitabine group and 8.1 months in the gemcitabine only group.
      The median progression-free survival was 8.0 months in the cisplatin plus
      gemcitabine group and 5.0 months in the gemcitabine-only group (p < 0.001).
      Adverse events were comparable in the two groups. Cisplatin plus gemcitabine,
      compared with gemcitabine alone, was associated with a significant survival
      advantage without an increase in substantial toxicity.

PMID- 20678013
TI  - Overview of the methods and therapies for the primary prevention of variceal
      bleeding.
AB  - Patients with cirrhosis develop varices at a rate of 5% per year, and a third of
      patients with high-risk varices will bleed. The mortality associated with
      variceal haemorrhage is typically 20%, and still exceeds that of myocardial
      infarction. Current options to prevent the first variceal bleed include
      noncardioselective beta-blockers or variceal band ligation. In patients with
      medium-to-large esophageal varices, both therapies reduce the risk of bleeding by
      50% or more. The choice of therapy should take into account patient choice and
      local availability; although for most patients drug therapy is the preferred
      first-line treatment. There has been recent interest in carvedilol, with
      promising initial data. Further studies are necessary before universal
      recommendation. There is no role for drug therapy in patients without varices,
      and the use of beta-blockers for patients with small varices is controversial.

PMID- 20678014
TI  - The growing incidence and severity of Clostridium difficile infection in
      inpatient and outpatient settings.
AB  - Clostridium difficile infection (CDI) is a leading cause of nosocomial
      infections, with disease severity ranging from mild diarrhea to fulminant
      colitis. The incidence and severity of CDI has been on the rise over the last 10
      20 years, with CDI being increasingly described outside healthcare settings and
      in populations previously thought to be at low risk. There has also been an
      increase in the morbidity, mortality and economic burden associated with CDI in
      the last several years. This increasing incidence and severity is thought to be
      at least partially due to frequent antibiotic use and the emergence of a
      hypervirulent C. difficile strain.

PMID- 20678015
TI  - The changing faces of endoscopic sedation.
AB  - The practice of sedation for digestive endoscopy continues to evolve throughout
      the world. In many countries, there is a trend for increased utilization of
      sedation during routine endoscopic procedures. Sedation improves patient
      satisfaction with endoscopy and the willingness to comply with screening
      guidelines and it improves the quality of examination. Moderate sedation, using a
      benzodiazepine and an opioid, remains the standard method of sedation in most
      areas of the world, although propofol, a short-acting hypnotic agent, is being
      used increasingly in some countries. Controversy regarding the feasibility of
      endoscopist-directed propofol administration continues, in spite of overwhelming
      evidence supporting this practice. In the USA, recent revisions in policy by the
      Centers for Medicare and Medicaid Services may threaten the practice of
      endoscopist-directed propofol administration. In this article, future trends in
      sedation practice, including fospropofol and computer-assisted personalized
      sedation, are discussed.

PMID- 20678016
TI  - The proton pump inhibitor test and the diagnosis of gastroesophageal reflux
      disease.
AB  - There continues to be significant controversy related to diagnostic testing for
      gastroesophageal reflux disease (GERD). Symptoms of GERD may be associated with
      physiologic esophageal acid exposure measured by intraesophageal pH monitoring or
      pH-impedance monitoring, and a significant percentage of patients with abnormal
      esophageal acid (or weak acid) exposure have no or minimal clinical symptoms of
      reflux. On the other hand, endoscopic lesions are only present in a minority of
      GERD patients. In clinical practice, presumptive diagnosis of GERD is reasonably
      assumed by the substantial reduction or elimination of suspected reflux symptoms
      during the therapeutic trial of acid reduction therapy, the so-called proton pump
      inhibitor (PPI) test. We aimed to assess the optimal cutoff value and duration of
      this test in GERD patients with and without esophagitis. We conducted a
      prospective study of 544 patients, endoscopically investigated and treated for 2
      weeks with PPIs at double dose, and for an additional 3 months at standard dose.
      The status of the patient at the end of the study was used as an independent
      diagnostic standard. We found esophagitis present in 55.8% and absent in 44.2% of
      patients (corresponding to a diagnosis of nonerosive reflux disease [NERD]). The
      test was positive in 89.7-97.8% of the patients according to the cutoff or
      duration of the test used. The sensitivity of the PPI test was excellent, ranging
      from 95.5 to 98.8%, whereas the specificity was poor, not exceeding 36.3%.
      Erosive esophagitis patients responded more favorably to the PPI test and
      subsequent PPI therapy compared with NERD patients. In conclusion, the PPI test
      is a sensitive but less specific test. Its optimal duration is 1 week, and the
      optimal cutoff value is a decrease of heartburn score of more than 75%. NERD
      patients respond less satisfactorily to PPIs, even when functional heartburn
      patients are excluded and only 'true' NERD patients are considered.

PMID- 20678017
TI  - Animal models of autoimmune hepatitis.
AB  - Animal models of autoimmune hepatitis have been important in defining pathogenic
      mechanisms, and they promise to aid in the evaluation of new molecular and
      cellular treatments. They have evolved from models based on crude liver
      homogenates that produced a transient hepatitis to models that express antibodies
      to human antigens, manifest liver-infiltrating T cells, persist for at least 3
      months and develop fibrosis. Animal models allow the study of autoimmune
      hepatitis from its inception, and they can detail the progression of pathological
      events. Key imbalances in counter-regulatory mechanisms can be isolated and
      manipulated. Models can be humanized by the insertion of human genetic promoters
      and the expression of human antigens. Genetic engineering and preconditioning
      have been milestones in the evolution of animal models. Vaccination or infection
      of murine models with viral vectors carrying human antigens are the most recent
      developments. Animal models promise to extend the knowledge of etiological agents
      and improve treatment algorithms.

PMID- 20678018
TI  - Hepatitis C virus recurrence after liver transplantation: biomarkers of disease
      and fibrosis progression.
AB  - End-stage liver disease due to hepatitis C virus infection (HCV) is the principal
      indication for liver transplantation. In the USA, over a third of available liver
      allografts are transplanted into recipients with chronic HCV infection.
      Reinfection of the graft is universal, but the impact of reinfection on short-
      and long-term liver function is highly variable. HCV infection in liver
      transplantation recipients is characterized by an accelerated fibrogenesis, with
      approximately a third of patients developing cirrhosis within 5 years of follow
      up. HCV is associated with decreased patient and graft survival when compared
      with other indications of orthotopic liver transplantation. The mechanisms
      responsible for the accelerated liver damage in HCV-infected orthotopic liver
      transplantation recipients remain largely unknown.

PMID- 20678019
TI  - Update on the pathophysiology of liver fibrosis.
AB  - Fibrogenesis represents the main pathophysiological consequence of chronic liver
      disease and leads to life-threatening clinical consequences. The knowledge in
      this field has grown exponentially in the past 20 years and, currently,
      evaluation and treatment of liver fibrosis are central issues in hepatology.
      Classic mechanisms of liver fibrogenesis have been expanded and consolidated over
      the past few years. Concomitantly, novel mechanisms have been suggested and
      demonstrated. The aim of this article is to provide an update on these mechanisms
      with an attempt to integrate classic and novel pathways responsible for the
      evolution of the fibrogenic process and, potentially, for its regression.

PMID- 20678020
TI  - Treatment options for primary sclerosing cholangitis.
AB  - Primary sclerosing cholangitis is a cholestatic liver disease characterized by
      inflammation and fibrosis of intra-/extrahepatic bile ducts, leading to
      multifocal strictures. Primary sclerosing cholangitis exhibits a progressive
      course resulting in cirrhosis and the need for liver transplantation over a
      median period of 12 years. The disease is frequently associated with inflammatory
      bowel disease and carries an increased risk of colorectal cancer and
      cholangiocarcinoma. Despite extensive research, there is currently no effective
      medical treatment. Multiple drugs are shown to be ineffective in halting disease
      progression, including ursodeoxycholic acid, the most widely evaluated drug. High
      dose ursodeoxycholic acid (28-30 mg/kg/day) was recently shown to increase the
      adverse events rate. Endoscopic or radiological dilatation of a 'dominant'
      stricture may lead to symptomatic and biochemical improvement. However, liver
      transplantation is the only life-prolonging treatment for patients with end-stage
      disease. Studies with promising drugs, such as antibiotics, antifibrotic agents
      and bile acid derivatives, are eagerly awaited.

PMID- 20678021
TI  - Portal vein embolization: rationale, outcomes, controversies and future
      directions.
AB  - Portal vein embolization (PVE) is now considered the standard of care to improve
      safety for patients undergoing extensive hepatectomy with an anticipated small
      future liver remnant (FLR). PVE is used to induce contralateral liver hypertrophy
      in preparation for major liver resection. Optimal patient selection is essential
      to maximize the clinical benefits of PVE. Computed tomography volumetry is used
      to calculate a standardized FLR and determine the need for preoperative PVE.
      Percutaneous PVE can be performed via the transhepatic ipsilateral or
      contralateral approaches, depending on operator preference. Several different
      embolic agents are available to the interventional radiologist, all with similar
      effectiveness in inducing hypertrophy. When an extended hepatectomy is planned,
      right PVE should include segment 4, in order to maximize FLR hypertrophy.
      Multiple studies have demonstrated the beneficial outcomes of PVE in both
      patients with healthy livers and with underlying liver diseases. Novel
      improvements to PVE should expand its scope to patients who were previously not
      candidates for the procedure.

PMID- 20678022
TI  - 10 years of capsule endoscopy: an update.
AB  - Capsule endoscopy (CE) has evolved in a few short years to become a first-line,
      noninvasive diagnostic technique for the small bowel. CE is now being utilized
      worldwide to assess patients for obscure gastrointestinal bleeding, possible
      Crohn's disease, celiac disease and small bowel tumors. The device is now used in
      tandem with balloon enteroscopy to direct therapeutic interventions. Alterations
      and improvements in CE have also led to the evaluation of both the esophagus and
      colon. It can be anticipated that in the near future pan CE of the entire GI
      tract will be performed, as well as possible tissue acquisition, drug delivery
      and therapeutic interventions.

PMID- 20678023
TI  - Scoring systems in inflammatory bowel disease.
AB  - Inflammatory bowel disease (IBD) is a chronic, relapsing condition affecting the
      GI tract that can affect individuals of any age and results in lifelong
      treatment, frequently including the need for surgery. Historically, the lack of a
      single effective and sensitive test for IBD has posed a great challenge in
      assessing disease severity, effectiveness of medication and predicting outcomes
      for this complex condition. Several IBD scoring and classification systems have
      been developed over many years to classify and characterize IBD patients, with
      the goal of helping to better define the disease status and effectiveness of
      therapy. Recent genetic investigations have revealed the complexity of IBD at the
      pathophysiologic level, revealing numerous genetic mutations associated with the
      disease. Thus, these clinically based IBD classification systems can provide the
      basis for the eventual correlation between the underlying genotype with clinical
      expression of disease and lead to better characterization of disease subtypes
      and, hopefully, customized treatment regimens.

PMID- 20678026
TI  - Periodontitis and cardiovascular diseases.
AB  - Periodontitis is characterized by gingival inflammation and periodontopathic
      bacteria generate immunological inflammatory responses. Recent epidemiological
      reports suggest that periodontitis is one of the key risk factors for the onset
      of cardiovascular diseases. Several studies reported that periodontal bacteria in
      cardiovascular specimens were frequently detected. We revealed that patients with
      acute coronary syndrome showed significantly higher serum IgG titers to a strain
      of periodontopathic bacteria compared with patients with chronic coronary
      disease. Periodontopathic bacteria were also present in a high percentage of
      specimens of diseased arteries from patients with Buerger disease or abdominal
      aortic aneurysm. Although periodontopathic bacteria may play a role in the
      development of cardiovascular diseases, the influence of these bacteria on the
      disease has not yet been proven. In this article, we review the relationship
      between periodontopathic pathogens and cardiovascular diseases to conduct further
      clinical and experimental investigations in near future.

PMID- 20678025
TI  - Selective targeting of RANK signaling pathways as new therapeutic strategies for
      osteoporosis.
AB  - IMPORTANCE OF THE FIELD: Osteoporosis has become a worldwide health and social
      issue due to an aging population. Four major antiresorptive drugs (agents capable
      of inhibiting osteoclast formation and/or function) are currently available on
      the market: estrogen, selective estrogen receptor modulators (SERMs),
      bisphosphonates and calcitonin. These drugs either lack satisfactory efficacy or
      have potential to cause serious side effects. Thus, development of more
      efficacious and safer drugs is warranted. AREAS COVERED IN THIS REVIEW: The
      discovery of the receptor activator of NF-kappaB ligand (RANKL) and its two
      receptors, RANK and osteoprotegerin (OPG), has not only established a crucial
      role for the RANKL/RANK/OPG axis in osteoclast biology but also created a great
      opportunity to develop new drugs targeting this system for osteoporosis therapy.
      This review focuses on discussion of therapeutic targeting of RANK signaling.
      WHAT THE READER WILL GAIN: An update on the functions of RANKL and an overview of
      the known RANK signaling pathways in osteoclasts. A discussion of rationales for
      exploring RANK signaling pathways as potent and specific therapeutic targets to
      promote future development of better drugs for osteoporosis. TAKE HOME MESSAGE:
      Several RANK signaling components have the potential to serve as potent and
      specific therapeutic targets for osteoporosis.

PMID- 20678028
TI  - Sociodemographic characteristics of cannabis smokers and the experience of
      cannabis withdrawal.
AB  - BACKGROUND: Cannabis withdrawal can be a negative reinforcer for relapse, but
      little is known about its association with demographic characteristics.
      OBJECTIVES: Evaluate the association of demographic characteristics with the
      experience of cannabis withdrawal. METHODS: Retrospective self-report of a
      "serious" cannabis quit attempt without formal treatment in a convenience sample
      of 104 non-treatment-seeking, adult cannabis smokers (mean age 35 years, 52%
      white, 78% male) with no other current substance use disorder (except tobacco) or
      chronic health problems. Reasons for quitting, coping strategies to help quit,
      and 18 specific withdrawal symptoms were assessed by questionnaire. RESULTS:
      Among withdrawal symptoms, only anxiety, increased sex drive, and craving showed
      significant associations with age, race, or sex. Women were more likely than men
      to report a physical withdrawal symptom (OR = 3.2, 95% CI = .99-10.4, p = .05),
      especially upset stomach. There were few significant demographic associations
      with coping strategies or reasons for quitting. CONCLUSIONS AND SCIENTIFIC
      SIGNIFICANCE: This small study suggests that there are few robust associations
      between demographic characteristics and cannabis withdrawal. Future studies with
      larger samples are needed. Attention to physical withdrawal symptoms in women may
      help promote abstinence.

PMID- 20678029
TI  - Transfer of myxovirus-protein-A mRNA assay for interferon-beta bioactivity
      measurement in multiple sclerosis patients to routine laboratory practice. A 4
      year experience.
AB  - BACKGROUND: As new biomarkers are validated and their significance in the natural
      history of specific diseases is established, these technologies can be rapidly
      transferred to clinical application. Since it has been shown that a single post
      interferon-beta (IFNbeta) injection measurement of myxovirus-protein-A (MxA) mRNA
      correlates with IFNbeta bioactivity in IFNbeta treated patients with multiple
      sclerosis (MS), we had previously validated an assay for its quantification.
      METHODS: We introduced a real-time PCR relative quantification assay into routine
      clinical practice and measured MxA mRNA expression in 564 samples from 500
      unselected IFNbeta treated MS patients over a 4-year period. RESULTS: We
      confirmed that the assay is reproducible over time, and found that the percentage
      of patients lacking MxA mRNA induction is comparable to that described in studies
      performed worldwide after patient selection by pre-screening for the presence of
      anti-IFNbeta antibodies. CONCLUSIONS: In view of its simplicity and
      reproducibility, this MxA assay is an alternative to anti-IFNbeta antibody
      determinations for use in routine clinical practice.

PMID- 20678030
TI  - Retrospective analysis of 88,429 serum and urine glucose EQA results obtained
      from professional laboratories and medical offices participating in surveys
      organized by three European EQA centers between 1996 and 2007.
AB  - BACKGROUND: The aim of this study was to provide inter-laboratory imprecision
      comparisons of different groups of diagnostic systems as well as a comparison of
      professional laboratories with medical offices performance on the basis of 88,429
      glucose results obtained in external quality assessment (EQA) schemes organized
      by three European EQA centers between 1996 and 2007. METHODS: A simple, non
      parametrical statistical model suited to all EQA results, including outliers, was
      used to calculate yearly and global performance. RESULTS: The best performance
      was obtained from professional laboratories with a group of three diagnostic
      systems--Hitachi, Integra, and Vitros, followed by Cobas Mira, and finally by
      Reflotron. For medical offices, the best performance was achieved with the Cobas
      Mira diagnostic systems, followed by the Reflotron, SpotChem, and Vitros DT60
      diagnostic systems. A slight but overall improvement in performance over time was
      observed for most diagnostic devices. CONCLUSIONS: The analysis of glucose EQA
      results collected over a 12-year period showed that professional laboratories
      obtained better performances than medical offices, and that a general improvement
      in yearly performance was observed for both types of laboratories.

PMID- 20678031
TI  - Effect of storage temperature or collection tube type on blood methylmalonic acid
      concentrations measured by gas chromatography-mass spectrometry.

PMID- 20678032
TI  - Liquid phase immunoassays utilizing magnetic markers and SQUID magnetometer.
AB  - BACKGROUND: Immunoassays are one main detection system used in the field of
      clinical chemistry. Recent developments of a new detection method utilizing a
      magnetic marker and magnetic sensor have enabled rapid and sensitive immunoassay
      without the need for bound/free (BF) separation. METHODS: Newly-synthesized
      conjugated avidin was used as the magnetic marker for quantitative analysis of
      human interleukin-8 (hIL-8) and immunoglobulin E (hIgE) in several media. A
      superconducting quantum interference device sensor detected the magnetic fields
      from markers fixed to antigens by the sandwich method. Magnetic signals from
      unbound markers were nearly zero due to Brownian rotation. RESULTS: Our magnetic
      immunoassay could detect four attomoles of model proteins (hIL-8, hIgE) in
      phosphate buffer without BF separation. Using our standard curve, the range of
      protein detected ranged from 40 femtomoles to 4 attomoles, and we observed a
      strong association between protein amounts and magnetic signals from the bound
      markers. The homogeneous immunoassay could also quantify three hundred cells from
      the fungus Candida albicans in phosphate buffer. CONCLUSIONS: The present study
      demonstrates the ability of magnetic markers for measuring biological targets
      without BF separation. This detection system has great potential for use as the
      next generation's analytical system.

PMID- 20678033
TI  - Spray-dried doxorubicin-albumin microparticulate systems for treatment of
      multidrug resistant melanomas.
AB  - As multidrug resistance continues to be a problem in cancer treatment, controlled
      release delivery systems, such as microspheres, may aid to give a slower release
      of anticancer drugs into drug resistant tumor cells. In this study doxorubicin
      microspheres microencapsulated in an albumin matrix were prepared via the spray
      drying method and characterized for particle size, content analysis, and release
      studies. They were then evaluated in vitro using drug resistant murine melanoma
      tumor cells for uptake and efflux studies. Spray-drying produced a dispersed
      powder with a mean particle size of 4.91 +/- 1.2 um, 60% product yield, and
      encapsulation efficiency of 85% and a zeta potential range of 37 to -40 mV.
      Intracellular doxorubicin concentrations were higher in drug resistant tumor
      cells treated with microspheres as opposed to solution, and efflux of doxorubicin
      from the tumor cell was inhibited. Greater cytotoxic effects were seen in tumor
      cells treated with doxorubicin microspheres versus solution up to and after 3
      days. In vivo pharmacokinetic studies conducted in male Sprague-Dawley rats,
      revealed a plasma-level time curve indicative of a two-compartment model, and
      showed prolonged half-life of doxorubicin, greater area under the plasma
      concentration time curve, and increased plasma concentrations of doxorubicin in
      rats at 8 and 24 h after administration of doxorubicin microspheres.

PMID- 20678034
TI  - Biodegradable levofloxacin nanoparticles for sustained ocular drug delivery.
AB  - Drug delivery to ocular region is a challenging task. Only 1-2% of drug is
      available in eye for therapeutic action, rest of the drug is drained out through
      nasolachrymal drainage system and other ocular physiological barriers. To
      overcome these problems of conventional dosage form, novel drug delivery systems
      are explored like nanoparticles. In our present work, levofloxacin encapsulated
      poly(lactic-co-glycolic acid) nanoparticles were developed and evaluated for
      various parameters like particle size, zeta potential, in vitro drug release and
      ex vivo transcorneal permeation. Microbiological efficacy was tested against
      Staphylococcus aureus using cup-plate method. Precorneal residence time was
      studied on albino rabbits by gamma scintigraphy after radiolabeling of
      levofloxacin by Tc-99m. Ocular tolerance was evaluated using hen's egg
      chorioallantoic membrane (HET-CAM) test. The developed nanoparticles were of
      spherical shape with a mean particle size of 190-195 nm with a zeta potential of 
      25 mV. The drug entrapment efficiency was found to be near 85%. In vitro drug
      release profile shows initial burst release followed by extended release up to 24
      h. Microbiological assay showed equivalent zone of inhibition compared to
      marketed formulation. gamma Scintigraphy images of developed formulation,
      suggested a good spread and good retention over precorneal area. The
      nanosuspension thus developed was retained for the longer time and drained out
      from the eye very slowly compared to marketed formulation as significant
      radioactivity was recorded in later in kidney and bladder. The developed
      nanosuspension with a mean score of 0.33 up to 24 h in HET-CAM assay, showed the
      nonirritant efficacy of developed formulation. The stability studies yielded a
      degradation constant less then 5 * 10(-4), proving a stable formulation with an
      arbitrary shelf life of 2 years.

PMID- 20678035
TI  - Recognising and responding to the obvious: the source of lead pollution at Mount
      Isa and the likely health impacts.

PMID- 20678036
TI  - Guidelines for youth depression: time to incorporate new perspectives.

PMID- 20678037
TI  - Rosiglitazone and cardiovascular disease revisited.

PMID- 20678038
TI  - Cultural safety in health for Aboriginal people: will it work in Australia?

PMID- 20678039
TI  - The burden of alcohol drinking on co-workers in the Australian workplace.
AB  - OBJECTIVE: To estimate the cost of the extra time worked by Australian workers
      due to their co-workers' alcohol drinking. DESIGN, SETTING AND PARTICIPANTS: A
      secondary analysis of data obtained from 1677 Australian workers aged 18 years or
      older collected as part of a broader national study into the third-party harms of
      alcohol. Computer-assisted telephone interviews were conducted between October
      and mid December 2008. MAIN OUTCOME MEASURES: Self-reported measures of the time
      spent covering for other people at work because of their alcohol drinking;
      measures of other impacts from co-workers' alcohol drinking; and self-reported
      income. RESULTS: Around a third of Australian workers have experienced negative
      effects from their co-workers' alcohol drinking, with 3.5% of workers reporting
      having to work extra hours to cover for others. The total annual cost to the
      Australian economy of this extra work is estimated to be $453 million.
      CONCLUSIONS: The results of this study suggest that Australian workers are
      significantly affected by other people's alcohol drinking, at considerable cost.
      This finding highlights the significant cost to the workplace of alcohol
      consumption, extending previous work which has focused only on alcohol-related
      absenteeism.

PMID- 20678040
TI  - The use of cross-jurisdictional population data to investigate health indicators
      of child maltreatment.
AB  - OBJECTIVES: To determine the extent to which children with a hospital admission
      related to assault or maltreatment or to a notified sexually transmitted
      infection (STI) have contact with the Western Australian Department for Child
      Protection (DCP), and to investigate injuries and conditions often associated
      with child maltreatment and subsequent contact with the DCP. DESIGN, PARTICIPANTS
      AND SETTING: Retrospective cohort study using de-identified, record-linked child
      protection and hospital morbidity data to identify all children aged 0-17 years
      in Western Australia between 1 January 1990 and 31 December 2005, and a subcohort
      of children born in WA between these dates, admissions of these children to
      public and private hospitals in WA, and their contact with the Western Australian
      DCP. MAIN OUTCOME MEASURES: Annual trends in notifications and substantiations of
      child maltreatment; proportion of children with assault-related and maltreatment
      related hospital admissions resulting in notifications, substantiations, or out
      of-home care. RESULTS: Most children admitted for maltreatment-related reasons
      (90%) had contact with the DCP, with 81% of these children being notified, 68%
      having maltreatment substantiated, and 50% entering out-of-home care. Specific
      injuries and conditions were associated with children who had greater contact
      with the DCP, including retinal haemorrhage, rib fractures, multiple injuries,
      STIs at under 14 years of age, and malnourishment. CONCLUSIONS: The health system
      effectively identifies and notifies real cases of maltreatment, and a high
      proportion of these are substantiated. Health data play an important role in
      improving maltreatment surveillance, providing opportunities to make valid
      comparisons over time and between jurisdictions, as well as to monitor conditions
      and injuries associated with child maltreatment.

PMID- 20678041
TI  - Health service attendance patterns in an urban Aboriginal health service.
AB  - OBJECTIVES: To describe the health service attendance patterns of urban
      Aboriginal and Torres Strait Islander (Aboriginal) Australians and make
      comparisons with those of the general Australian population. DESIGN AND SETTING:
      General practitioner-completed survey of all attendances over two separate 2-week
      periods in 2006 at an urban Aboriginal health service in Canberra, which provides
      services for about 3500 patients per annum. MAIN OUTCOME MEASURES: Standardised
      attendance ratios (SARs) for a range of health problems, using patients attending
      Australian general practice for the same reasons as the reference population.
      RESULTS: Patients attending the Aboriginal health service were significantly
      younger than the Australian general practice patient reference population. The
      most common conditions managed were psychological, encompassing substance misuse;
      psychological problems accounted for 24% of all attendances. Patients attending
      the Aboriginal health service had higher rates of attendance for psychological
      conditions (SAR, 2.14; 95% CI, 2.01-2.28), endocrine conditions (SAR, 2.44; 95%
      CI, 2.29-2.60) and neurological conditions (SAR, 2.90; 95% CI, 2.71-3.09), as
      well as for circulatory, digestive and male and female genital conditions, than
      the reference population. Patients attending the Aboriginal health service had
      significantly lower attendance rates than the Australian population for
      respiratory illnesses, and conditions related to eyes or ears. CONCLUSIONS: At
      this urban Aboriginal health service, attendance patterns reflected complex
      health care needs that are different from those expected of a population of this
      age. Urban Aboriginal health service attendance appears to reflect significant
      ill health among the patients, aligning more with Aboriginal health statistics
      nationally rather than health statistics for urban non-Aboriginal Australians.

PMID- 20678042
TI  - A multimodal intervention to improve fragility fracture management in patients
      presenting to emergency departments.
AB  - OBJECTIVE: To implement and evaluate a multimodal intervention to improve
      osteoporosis treatment in patients with a fragility fracture. DESIGN, SETTING AND
      PARTICIPANTS: Strategies to improve the management of patients discharged from an
      emergency department after presentation with fragility fracture were implemented
      prospectively in a large tertiary public hospital. Patients were surveyed by post
      to assess their awareness of osteoporosis and of the need for treatment. General
      practitioners and hospital clinicians completed an online questionnaire about
      their attitudes to osteoporosis and its management. A simplified consensus
      guideline was developed for local use. Our study was conducted between 1 October
      2007 and 31 October 2008. MAIN OUTCOME MEASURES: Rates of referral of patients
      for osteoporosis review; rates of investigation and treatment. RESULTS: Although
      most GPs (259/306 [85%]) accepted that it was their responsibility to assess and
      treat their patients and inform them of their osteoporosis risk, only 35/87
      patients (40%) indicated awareness of their risk. After implementation of our
      project, the rate of bone mineral densitometry investigations improved from 6/200
      (3%) to 39/87 (45%) (P < 0.05). The number of patients receiving calcium and
      vitamin D supplementation increased from 24/200 (12%) (for both supplements) to
      29/87 (33%) and 32/87 (37%), respectively (P < 0.05). Initiation of specific
      treatments increased from 12/200 (6%) to 26/87 (30%) (P < 0.05). Referral of
      eligible patients to the Fragile Bone Clinic for osteoporosis review improved
      from 20/500 (4%) to 51/194 (26%). After being contacted by a fracture liaison
      nurse, 84% of these patients presented for osteoporosis review in the clinic.
      CONCLUSIONS: A major key to improving osteoporosis management is to actively
      identify all patients at risk and proactively engage and encourage them to seek
      assessment and management. A multimodal strategy involving a dedicated fracture
      liaison nurse may offer the greatest potential for improving education and
      patient follow-up and treatment.

PMID- 20678043
TI  - Impact of adverse news media on prescriptions for osteoporosis: effect on
      fractures and mortality.
AB  - OBJECTIVE: To examine the impact of a national current affairs television program
      about the association between osteonecrosis of the jaw and bisphosphonates on
      subsequent prescription use, fractures and deaths. DESIGN AND SETTING: National
      Pharmaceutical Benefits Scheme prescription data for 9 months after the
      television program were used to estimate the impact of reduced bisphosphonate use
      on fractures and mortality. MAIN OUTCOME MEASURES: Prescription rates, fractures
      and deaths. RESULTS: The estimated reduction of 29 633 in the number of
      bisphosphonate prescriptions may have resulted in 70 hip fractures, 60 other
      fractures and 14 deaths that would otherwise have been prevented over the 9-month
      period of the study. CONCLUSION: Although it is important for patients to be
      informed of the risks of medication, media coverage that does not present a
      balanced view has the potential to do more harm than good.

PMID- 20678044
TI  - Ethical considerations in choosing a model for population-based cystic fibrosis
      carrier screening.
AB  - Cystic fibrosis (CF) carrier testing can be used to inform reproductive decision
      making, allowing carriers to avoid having a child with CF. A government-funded,
      population-based CF carrier screening program would allow greater equity of
      access to this test. The setting in which CF carrier screening is offered
      significantly affects the extent to which participants make well informed,
      voluntary decisions to accept or decline testing. Screening offered before
      pregnancy and in non-clinical environments better promotes participant autonomy
      than screening offered in the prenatal consultation.

PMID- 20678045
TI  - Factors associated with psychiatric morbidity and hazardous alcohol use in
      Australian doctors.
AB  - OBJECTIVE: To identify factors associated with psychiatric morbidity and
      hazardous alcohol use in Australian doctors. DESIGN, SETTING AND PARTICIPANTS:
      Cross-sectional postal survey of 2999 doctors (including all major specialty
      groups, trainees and general practitioners) insured with an Australian medical
      insurance company. The potential for psychiatric morbidity was measured by the
      General Health Questionnaire (GHQ), and the potential for hazardous alcohol use
      by the Alcohol Use Disorders Identification Test (AUDIT). The survey was
      conducted in 2007. MAIN OUTCOME MEASURES: Demographic, work-related and
      personality factors associated with a GHQ score > 4 and an AUDIT score > or = 8.
      RESULTS: Factors significantly associated with psychiatric morbidity in doctors
      were: having a current medicolegal matter, not taking a holiday in the previous
      year, working long hours, type of specialty, and having personality traits of
      neuroticism and introversion. Factors significantly associated with potentially
      hazardous alcohol use were being male, being Australian-trained, being between 40
      and 49 years of age, having personality traits of neuroticism and extroversion,
      failing to meet Continuing Medical Education requirements, and being a solo
      practitioner. CONCLUSIONS: The mental health of medical practitioners is crucial
      to the quality of care their patients receive. Doctors should reflect on their
      hours of work and need for holidays. Involvement with medicolegal processes, such
      as lawsuits, complaints and inquiries, is a stressful part of medical practice
      today. Doctors need to be educated about these processes and understand how the
      experience may affect their health, work and loved ones.

PMID- 20678046
TI  - Lost opportunities with Australia's health workforce?
AB  - Concerns have been raised about the capacity of the health workforce to meet
      increasing future health care demands. Strategies aimed at improving workforce
      supply, at least in Australia, are focused heavily on education (ie, increasing
      the number of training places in key health professions) and recruitment (ie,
      recruiting overseas-trained health care professionals). Data from the 2006
      Australian Bureau of Statistics census of population and housing indicate that
      while many Australians hold health professional qualifications, many are either
      not in the workforce or not employed within the health occupation they hold
      qualifications for. Some immediate solutions for increasing the health workforce
      are to attract qualified health professionals who are either not in the workforce
      or are working outside the health occupation back into their occupational role;
      to increase worker retention for those still working within the occupations they
      trained for; and to explore strategies for better retention of new graduates.

PMID- 20678047
TI  - Treatment for osteoporosis in Australian residential aged care facilities:
      consensus recommendations for fracture prevention.
AB  - Older people living in residential aged care facilities (RACFs) are at
      considerably higher risk of suffering fractures than older people living in the
      community. When admitted to RACFs, patients should be assessed for fracture risk
      to ensure early implementation of effective fracture prevention measures. Routine
      or regular determination of calcium and phosphate serum levels in
      institutionalised older people is not indicated. Opinion is divided about the
      value of routine measurements of serum concentrations of 25-hydroxyvitamin D,
      parathyroid hormone and bone turnover markers. The non-pharmacological approach
      to fracture prevention includes multifactorial programs of falls prevention and
      the use of hip protectors. Vitamin D supplementation is recommended for all
      patients in RACFs. Dietary calcium intake should be optimised (1200-1500 mg per
      day is recommended) and supplementation offered to those with inadequate intake.
      The decision to prescribe calcium supplements should be guided by patients'
      tolerance, whether or not they have a history of kidney stones, and emerging data
      about its cardiovascular safety. Bisphosphonates are the first-choice
      pharmacological agents for fracture prevention in older persons at high risk.
      Intravenous administration is as efficient as oral and has the significant
      advantage of better adherence. Use of strontium ranelate has not been tested on
      people in RACFs, but evidence in the "old-old" (those aged 75 years and older)
      suggests it could be a therapeutic option for fracture prevention in this
      setting. In general, teriparatide should not be considered as a first-line
      treatment for fracture prevention, particularly for people in RACFs.

PMID- 20678048
TI  - Cutaneous marker of an upper gastrointestinal bleed.

PMID- 20678049
TI  - Frightening visual hallucinations: atypical presentation of Charles Bonnet
      syndrome triggered by the Black Saturday bushfires.
AB  - Charles Bonnet syndrome (CBS) is a disorder in which psychologically normal
      people, often with vision impairment, experience complex visual hallucinations.
      The hallucinations are purely visual and do not occur in any other sensory
      modality, and people with CBS have full insight into the unreal nature of the
      hallucinations. This report describes the case of a CBS sufferer who experienced
      a distressing change in the nature of her visual hallucinations following a
      stressful event--the Black Saturday bushfires of February 2009.

PMID- 20678050
TI  - Suicide and mental disorder: the legal perspective.

PMID- 20678051
TI  - Subconjunctival dog heartworm.

PMID- 20678052
TI  - Current concepts in the management of Parkinson disease.

PMID- 20678053
TI  - Invisible people?

PMID- 20678054
TI  - Expiry of patent protection on statins: effects on pharmaceutical expenditure in
      Australia. Comment.

PMID- 20678055
TI  - Urban-rural comparison of weight status among women and children living in
      socioeconomically disadvantaged neighbourhoods. Comment.

PMID- 20678056
TI  - Does access to compensation have an impact on recovery outcomes after injury?
      Comment.

PMID- 20678057
TI  - Homeopathy: what does the "best" evidence tell us? Comment.

PMID- 20678058
TI  - Achieving standardised reporting of suicide in Australia: rationale and program
      for change. Comment.

PMID- 20678059
TI  - Junk food packaging--a challenge to the Prime Minister. Comment.

PMID- 20678060
TI  - Stem cells: clinical trials results the end of the beginning or the beginning of
      the end?
AB  - With increasing focus on the advance towards curative solutions, it is hard not
      to be excited by the potential of stem cell-based therapy. Application of the
      stem cell paradigm to cardiovascular medicine has fostered the evolution of novel
      approaches aimed at reversing injury caused by ischemic and non-ischemic
      cardiomyopathy. The feasibility and safety of stem cell use has been established
      in over 3,000 patients with either recent myocardial infarction or chronic organ
      failure. Nonetheless, the efficacy of stem cell therapy continues to remain in
      question. Initial clinical trials have focused on evaluation of multiple adult
      stem cell phenotypes in their unaltered, naive state as a "first generation"
      resource for repair. Though significant strides in perfecting delivery of these
      biologics to the diseased heart have been achieved, the benefits with regard to
      myocardial functional recovery have been modest at best. One approach towards
      optimizing outcome may lie upon preemptive guidance of stem cells down the
      pathway of myocyte regeneration. As seen with pharmacotherapeutics in the last
      century, successful translation of "second generation" biotherapeutics in the
      21(st) century will require close integration of a community of practice and
      science to ensure broad application of this emerging technology in the treatment
      of heart disease.

PMID- 20678061
TI  - Resident and non-resident stem cells in acute myocardial infarction.
AB  - Cardiovascular disease is the leading cause of death in developed countries.
      Acute myocardial infarction (AMI) is the result of hypoxia leading to
      cardiomyocyte death. This causes loss of function of contractile tissue, which is
      replaced by non-contractile fibrous tissue affecting left ventricular ejection
      fraction (LVEF). One of the current approaches to recover LVEF after an AMI is
      focused on the search for functional cells to replace the dead tissue, via
      implantation in the heart of autologous progenitor cells with a regenerative
      capacity. This review classifies these cells into two types: a) non-resident
      cells and b) resident cells within the cardiac tissue. We provide an overall view
      of the various subpopulations and their markers, based, in animal and human
      models from the early pioneering work to the latest findings.

PMID- 20678062
TI  - Stem cell-based therapies for heart regeneration: what did the bench teach us?
AB  - Stem cell-based therapies represent a promising therapy for myocardial
      infarction. Pre-clinical and clinical tests performed in the last 10 years
      indicate that several types of stem cells and their progenies reduce infarct size
      and improve cardiac contractile function. The mechanism is dependent on the type
      of cell and involves a combination of several factors, such as: (i) the formation
      of new blood vessels, (ii) the release of pro-survival, pro-angiogenic and anti
      inflammatory factors (paracrine effect), and (iii) the functional contribution of
      cardiomyocytes. With the exception of cardiac progenitor cells and pluripotent
      stem cells (human embryonic stem cells and inducible pluripotent stem cells) that
      have the unquestioned ability to give rise to cardiomyocytes, the other stem
      cells, including bone-marrow stem cells and fetal stem cells, have none or very
      limited capacity to differentiate into contractile cells. For both cases, it is
      of the utmost importance to develop strategies to promote cell survival and in
      vivo engraftment as well as to unravel the therapeutic mechanism of stem cells.
      This review focuses on the recent developments of stem cells and on the use of
      biomaterials for efficiently stem cell delivery and tracking.

PMID- 20678063
TI  - Challenges in vascular repair by endothelial progenitor cells in diabetic
      patients.
AB  - Endothelial progenitor cells (EPCs) are a special type of stem cells, derived
      from bone marrow that can be mobilized to the peripheral circulation in response
      to many stimuli. EPCs play a crucial role in the vascular repair, as well as in
      neovascularization processes. Recent studies have shown that EPCs are impaired,
      both in number and function, in diabetic patients independently of other
      cardiovascular risk factors. Accelerated atherosclerosis is probably the most
      devastating among diabetes complications and endothelial dysfunction might be the
      beginning of the atherosclerosis. The impairment of EPCs seems to significantly
      contribute to atherogenesis and atherosclerotic disease progression in diabetes.
      Autologous EPCs therapy represents a novel treatment option for vascular
      complications requiring therapeutic revascularization and vascular repair.
      Diabetic patients represent a population that may benefit from cell-based
      therapy; however the dysfunction of their endogenous cells may limit the
      feasibility of this approach. In fact, EPCs isolated from these patients for
      autologous cell transplantation may retain their dysfunctional characteristics in
      vivo and as a consequence display a reduced capacity to improve therapeutic
      neovascularization. In the present review, we summarize the most relevant
      mechanisms of EPC dysfunction in diabetes.

PMID- 20678064
TI  - Stem cell therapy in chronic ischemic heart dysfunction with and without
      viability.
AB  - A growing number of clinical trials are evaluating the effects of stem cell
      therapy in patients with chronic ischemic heart dysfunction. As most of the
      clinical trials included a limited and different number of patients, various stem
      cell sources and several delivery approaches, results vary substantially between
      these studies. We analyse whether the assessment of myocardial viability may be
      important when evaluating effects of stem cell transplantation on parameters of
      left ventricular remodeling. Viability assessment could help to find the best
      type of stem cell and the best method of cell delivery to be used in chronic
      ischemic heart dysfunction.

PMID- 20678065
TI  - Protein kinase C - possible therapeutic target to treat cardiovascular diseases.
AB  - Cardiovascular diseases (CVDs) such as atherosclerosis, hypertension and
      diabetes, are major global health problems and one of the leading causes of
      death. Thrombosis associated with multiple CVDs such as atherosclerosis and
      diabetes further increase morbidity by causing myocardial infarction or stroke.
      The members of Protein Kinase C (PKC) family are serine threonine kinases,
      abundantly expressed in cells that maintain cardiovascular health. Studies done
      using pharmacological tools that block wide range of PKCs or specific PKC
      isoforms and PKC gene knockout animals revealed that these enzymes regulate
      critical functional responses in cardiovascular cells. Interestingly, PKC isotype
      activity is context specific and PKC isotypes may have opposing functional roles
      depending on cell type and cellular environment (eg., cardiomyocytes, platelets).
      Furthermore, precise structural differences that occur amongst these isoforms
      have lead to development of compounds that inhibit or activate specific PKC
      isoforms. Thus, it is feasible to enhance the protective effects of a PKC
      isoform, while minimizing the damage caused by other members of PKC family. In
      this review, we summarize the role of each of these PKC isoforms in various
      cardiovascular diseases. In addition, we detail the specific PKC isoform
      modulators, their mechanism of action and ability to treat cardiovascular
      diseases, as evaluated in animal models or human subjects.

PMID- 20678066
TI  - New insight in antiplatelet therapy monitoring in cardiovascular patients: from
      aspirin to thienopyridine.
AB  - Antiplatelet therapy is used to reduce the risk of ischemic events in patients
      with cardiovascular disease. The balance of benefits and risks of antiplatelet
      drugs in cardiovascular disease has been evaluated in large-scale randomised
      trials, however the absolute benefit for an individual patient and a specific
      platelet-active drug needs further evaluation. Several well-conducted studies
      have demonstrated a substantial inter-individual variability in platelet
      responsiveness to drugs. The historical "gold standard" test of platelet function
      (optical aggregation) has been extensively used for measuring the effect of
      antiplatelet drugs, but has limitations. New tests developed (i.e. PFA-100(r),
      VerifyNow(r)) may overcome some of these limitations but they do not correlate
      well with each other. Despite these unresolved methodological questions, several
      recent clinical studies, but not all, suggest a significant correlation between
      antiplatelet resistance status and serious vascular events. In these conditions,
      laboratory monitoring for antiplatelet therapies raises several questions: (i)
      the necessity of a consensus regarding the definition of resistance and the
      relevant test, (ii) the demonstration that biological resistance has clinical
      significance, and (iii) the clinical impact of individually adjusting the
      antiplatelet therapy. Therefore, it is not currently appropriate to test patients
      or to change therapy on the basis of such tests, other than in prospective and
      adequately powered clinical trials.

PMID- 20678067
TI  - Hypothermia and Alzheimer's disease neuropathogenic pathways.
AB  - Alzheimer's disease (AD) remains a major health problem, and accounts for 50 to
      60% of all cases of dementia. The two histopathological hallmarks of AD are
      senile plaques, composed of the beta-amyloid peptide (Abeta), and intraneuronal
      neurofibrillary tangles composed of abnormally hyperphosphorylated tau protein.
      Only a small proportion of AD is due to mutations in the genome of patients, the
      large majority of cases being of late onset and sporadic in origin. The relative
      contribution of genetics and environment to the sporadic cases is unclear, but
      they are accepted to be of multifactorial origin. This means that genetic and
      environmental factors can interact together to induce or accelerate the disease.
      Among environmental factors, studies suggest that hypothermia may contribute to
      the development and exacerbation AD. Here, we review the preclinical data
      involving hypothermia with tau and Abeta, as well as clinical evidence
      implicating hypothermia in the development of AD.

PMID- 20678068
TI  - Intra- and extracellular protein interactions with tau.
AB  - Tau is a sticky protein mainly expressed by neurons, which may be found in
      different subcellular fractions or outside the cell. Tau is mainly associated to
      microtubules in the cytoplasm, although besides tubulin, tau can also bind to
      other proteins and to itself to form different polymers, some of which are
      relevant in pathological disorders. In this short review, we have revised some of
      the interactions involving tau, both inside or outside of the cell. Different
      regions of tau are involved in these interactions and some of them are more
      conserved throughout evolution than others.

PMID- 20678069
TI  - Tau pathology and future therapeutics.
AB  - The current review discusses microtubules and tau in the healthy brain and move
      on to the underling pathology of Alzheimer's disease (AD) with emphasis on tau
      and neurofibrillary tangles. Tangles have been associated with cognitive
      dysfunction causing neurodegeneration in the absence of plaques. AD, the most
      abundant tauopathy is characterized by beta-amyloid plaques and tau tangles. An
      abundance of tau inclusions, in the absence of beta-amyloid deposits, defines
      Pick's disease (frontotemporal lobar degeneration), progressive supranuclear
      palsy (PSP), corticobasal degeneration (CBD) and other diseases. Our own focused
      research is on activity-dependent neuroprtective protein (ADNP). Our findings
      show that ADNP-deficiency leads to tauopathy which is inhibited by the ADNP
      derived drug candidate, davunetide (originally known as NAP). The current review
      further describes tau as a potential diagnostic marker followed by drug
      candidates that are aimed at fighting tau pathology. A recent historical
      perspective is the final comment of the manuscript. This paper is not a
      comprehensive review of the literature rather it gives my own point of view in
      the face of many publications and a great unmet need for future therapeutics. It
      is hoped that davunetide, a most advanced drug in clinical development will
      rapidly advance as a first effective treatment for a number of brain disorders
      broadly categorized as frontotemporal dementia (FTD) and serve as a prototype for
      future therapeutic development toward modification and remedy of currently
      intractable neurodegenerative diseases.

PMID- 20678070
TI  - Tau aggregation is a therapeutic target for Alzheimer's disease.
AB  - Based on the amyloid hypothesis, studies for AD therapy have been mostly focused
      on removing beta-amyloid. Recent results of amyloid immunotherapy raised the
      question whether beta-amyloid is sufficient target for AD therapy.
      Neurofibrillary tangles (NFTs), which contain hyperphosphorylated tau, are
      another pathological hallmark of AD. NFTs are observed in entorhinal cortex,
      limbic, and neocortex over the course of clinical progression. NFTs are
      associated with synapse and neuron loss, suggesting that the process of NFT
      formation is involved in brain dysfunction. During NFT formation, tau forms a
      variety of different aggregation species, including tau oligomers, granules, and
      fibrils. Analysis of different human tau-expressing mouse lines reveals that
      soluble hyperphosphorylated tau, which includes tau oligomer, is involved in
      synapse loss, whereas granular tau formation is involved in neuronal loss.
      Therefore, inhibition of tau aggregation and tau phosphorylation is expected to
      prevent synapse loss and neuron loss, and may slow or halt the progressive
      dementia in AD.

PMID- 20678071
TI  - Tau truncation is a productive posttranslational modification of neurofibrillary
      degeneration in Alzheimer's disease.
AB  - Deposits of the misfolded neuronal protein tau are major hallmarks of
      neurodegeneration in Alzheimer's disease (AD) and other tauopathies. The etiology
      of the transformation process of the intrinsically disordered soluble protein tau
      into the insoluble misordered aggregate has attracted much attention. Tau
      undergoes multiple modifications in AD, most notably hyperphosphorylation and
      truncation. Hyperphosphorylation is widely regarded as the hottest candidate for
      the inducer of the neurofibrillary pathology. However, the true nature of the
      impetus that initiates the whole process in the human brains remains unknown. In
      AD, several site-specific tau cleavages were identified and became connected to
      the progression of the disease. In addition, western blot analyses of tau species
      in AD brains reveal multitudes of various truncated forms. In this review we
      summarize evidence showing that tau truncation alone is sufficient to induce the
      complete cascade of neurofibrillary pathology, including hyperphosphorylation and
      accumulation of misfolded insoluble forms of tau. Therefore, proteolytical
      abnormalities in the stressed neurons and production of aberrant tau cleavage
      products deserve closer attention and should be considered as early therapeutic
      targets for Alzheimer's disease.

PMID- 20678072
TI  - Targeting heat shock proteins in tauopathies.
AB  - Heat shock proteins are members of a large family that function normally in
      nascent protein folding and the removal of damaged proteins and are able to
      respond to cellular stresses such as thermal insult to prevent catastrophic
      protein aggregation. A number of the most common neurodegenerative disorders such
      as Alzheimer's and Parkinson's diseases are characterized by such abnormal
      protein folding and aggregation, and the induction of the heat shock response is
      observed in these cases through their increased expression and often localization
      within the inclusions. Tau proteins form the major structural component of the
      neurofibrillary protein aggregates that correlate with cognitive decline in
      Alzheimer's disease, and appropriately this abnormal tau is targeted for
      corrective action by the heat shock proteins that recognize sequence motifs that
      are normally masked though microtubule binding. This specific heat shock response
      to the formation of abnormal tau can also be targeted pharmacologically to
      inhibit the refolding pathways and drive the degradation of tau species that are
      thought to be pathogenic. This review discusses the recent advances of the roles
      of heat shock proteins in this process.

PMID- 20678073
TI  - Tubulin-independent tau in Alzheimer's disease and cancer: implications for
      disease pathogenesis and treatment.
AB  - Microtubule-associated protein tau has long been known for its ability to promote
      microtubule assembly. A less known feature of tau is its existence as a non
      microtubule associated protein. Here we review the interactions of tau with other
      proteins, some of which interact with the microtubule binding repeat region of
      tau. The tau interactions with Fyn and with Pin1 have attracted the most
      attention and both interactions have been thought to have a role in Alzheimer's
      disease. The fact that tau has unknown cellular functions is further evidenced by
      its involvement in cell cycle activated neurodegeneration. One possible route for
      additional investigations stems from the presence of tau in non-neuronal cells
      where its characteristics have been largely unknown, although there has been a
      correlation between tau levels and the response of some cancer cells to
      microtubule-targeting chemotherapy drugs. Our studies of prostate cancer cells
      indicate that these cells can provide a system with phosphorylated adult tau for
      functional studies. In fact, structural similarities exist between Alzheimer's
      disease tau and prostate cancer cell tau, raising the possibility that new tau
      functions uncovered in prostate cancer cells will have relevance to Alzheimer's
      disease.

PMID- 20678075
TI  - Classification of genomic sequences via wavelet variance and a self-organizing
      map with an application to mitochondrial DNA.
AB  - We present a new methodology for discriminating genomic symbolic sequences, which
      combines wavelet analysis and a self-organizing map algorithm. Wavelets are used
      to extract variation across various scales in the oligonucleotide patterns of a
      sequence. The variation is quantified by the estimated wavelet variance, which
      yields a feature vector. Feature vectors obtained from many genomic sequences,
      possibly of different lengths, are then classified with a nonparametric self
      organizing map scheme. When applied to nearly 200 entire mitochondrial DNA
      sequences, or their fragments, the method predicts species taxonomic group
      membership very well, and allows the results to be visualized. When only
      thousands of nucleotides are available, wavelet-based feature vectors of short
      oligonucleotide patterns are more efficient in discrimination than frequency
      based feature vectors of long patterns. This new data analysis strategy could be
      extended to numeric genomic data. The routines needed to perform the computations
      are readily available in two packages of software R.

PMID- 20678076
TI  - Confidently estimating the number of DNA replication origins.
AB  - We present a method for estimating and providing a confidence interval for the
      number of DNA replication origins in the genome of the yeast Kluyveromyces
      lactis. The method requires an initial set of verified sites from which a
      position specific frequency matrix (PSFM) can be constructed. We further assume
      that we have access to a sparingly used experimental procedure which can verify
      the functionality of a few, but not all, computationally predicted sites. While
      our motivation comes from estimating the number of autonomously replicating
      sequences (ARSs), our method can also be applied to estimating the genome-wide
      number of "functional" transcription factor binding sites, where functionality is
      determined by experimental verification of the transcription factor binding event
      using, for example, ChIP data. The reliability of our method is demonstrated by
      correctly predicting the known number of Saccharomyces cerevisiae ARSs as well as
      the number of S. cerevisiae probes that bind to the transcription factor ABF1.

PMID- 20678077
TI  - The one-to-one relationship: is it really key to an effective preceptorship
      experience? A review of the literature.
AB  - Currently, considerable focus is directed at improving clinical experiences for
      nursing students, with emphasis placed on adequate support and supervision for
      the purpose of creating competent and safe beginning practitioners. Preceptors
      play a vital role in supporting, teaching, supervising and assessing students in
      clinical settings as they transition to the graduate nurse role. Intrinsic to
      this model is the assumption that the one-to-one relationship provides the most
      effective mechanism for learning. With the current Registered Nurses (RN)
      shortage, among other factors, the one-to-one relationship may not be feasible or
      as advantageous to the student. Thus, nurse educators need to carefully assess
      how this relationship is configured and maintained to assist them in fostering
      its evolution. In this review of the literature, the authors explore the
      assumption that a one-to-one relationship in the preceptorship experience fosters
      a rich and successful learning environment, and implications for nursing
      education, practice and research are outlined.

PMID- 20678078
TI  - Creating a path: American Indian/Alaska Native high school students pursuing
      college and a career in nursing.
AB  - The purpose of this quantitative descriptive pre- and post-survey study was to
      analyze four years of data documenting differences in pre- and post-test
      responses by American Indian/Alaska Native high school students attending a
      weeklong residency program. The program was designed to provide information and
      role models to motivate students to go to college and pursue a career in nursing.
      The survey measured student perceptions of college and nursing. In addition, the
      analysis included comparisons of responses between students who lived on
      reservations and those who did not. Results demonstrated that students changed
      their views of nursing as a profession, how they would be perceived by their
      tribe, and the financial security they could gain. Students living on their
      reservations were concerned that college might be too far from home.
      Recommendations include the need to provide indigenous students with role models
      and accurate information as well as mentors to support them.

PMID- 20678074
TI  - Tau in Alzheimer disease and related tauopathies.
AB  - Tau is the major microtubule associated protein (MAP) of a mature neuron. The
      other two neuronal MAPs are MAP1 and MAP2. An established function of MAPs is
      their interaction with tubulin and promotion of its assembly into microtubules
      and stabilization of the microtubule network. The microtubule assembly promoting
      activity of tau, a phosphoprotein, is regulated by its degree of phosphorylation.
      Normal adult human brain tau contains 2-3 moles phosphate/mole of tau protein.
      Hyperphosphorylation of tau depresses this biological activity of tau. In
      Alzheimer disease (AD) brain tau is ~three to four-fold more hyperphosphorylated
      than the normal adult brain tau and in this hyperphosphorylated state it is
      polymerized into paired helical filaments ([PHF) admixed with straight filaments
      (SF) forming neurofibrillary tangles. Tau is transiently hyperphosphorylated
      during development and during anesthesia and hypothermia but not to the same
      state as in AD brain. The abnormally hyperphosphorylated tau in AD brain is
      distinguished from transiently hyperphosphorylated tau by its ability (1) to
      sequester normal tau, MAP1 and MAP2 and disrupt microtubules, and (2) to self
      assemble into PHF/SF. The cytosolic abnormally hyperphosphorylated tau, because
      of oligomerization, unlike normal tau, is sedimentable and on self-assembly into
      PHF/SF, loses its ability to sequester normal MAPs. Some of the tau in AD brain
      is truncated which also promotes its self-assembly. Tau mutations found in
      frontotemporal dementia apparently promote its abnormal hyperphosphorylation.
      Thus, the AD abnormally hyperphosphorylated tau (1) is distinguishable from both
      normal and transiently hyperphosphorylated taus, and (2) is inhibitory when in a
      cytosolic/oligomeric state but not when it is self-assembled into PHF/SF.
      Inhibition of abnormal hyperphosphorylation of tau offers a promising therapeutic
      target for AD and related tauopathies.

PMID- 20678079
TI  - The intention to pursue graduate studies in nursing: a look at BScN students'
      self-efficacy and value influences.
AB  - The shortage of graduate-level prepared nurses is reaching critical levels.
      Combined with an anticipated wave of faculty retirements, a relatively older
      graduate student body, and an insufficient number of graduates at the Masters'
      and doctoral levels, the recruitment of more and younger students into graduate
      programs in nursing has become a priority for the profession. Current
      understanding of why undergraduate nursing students choose to pursue graduate
      studies in nursing remains vague. A non-experimental descriptive correlational
      study was designed and 87 useable surveys were collected from fourth-year
      baccalaureate nursing students at a large South-Western Ontario University
      (response rate = 67%). The influence of student valuation of graduate studies and
      self-efficacy (SE) for graduate studies on student intention to pursue graduate
      studies in nursing was clearly demonstrated with this study (R(2) = .52).
      Implications for nursing education include working towards undergraduate
      curricula that enhance students' valuation of and SE for graduate studies in
      nursing.

PMID- 20678080
TI  - Reforming perspectives: MSN graduates' knowledge, attitudes and awareness of self
      transformation.
AB  - Socialization includes internalization of attitudes and values critical to the
      development of a professional identity. Resocialization relates to the returning
      registered nurse student's development of professional values and roles. Nurse
      educators' challenge is to consider socialization/resocialization as a
      formation/re-formation process. The purpose of this article is to report findings
      from a replication qualitative descriptive study that examined the process of
      change in knowledge and attitudes of recent MSN graduates using Mezirow's
      (1994)Transformative Learning Theory. Findings substantiated the changes in
      attitudes, knowledge and skills of MSN graduates identified by Cragg and
      Andrusyszyn (2005). Results further inform nurse educators of the process of
      transformation in MSN graduates according to Mezirow's Phases of Perspective
      Transformation.

PMID- 20678081
TI  - Being cabezona: success strategies of Hispanic nursing students.
AB  - Hispanic registered nurses (RNs) are poorly represented in professional nursing,
      comprising only 1.7% of RNs despite representing 15% of the population of the
      United States. Furthermore, their numbers are actually decreasing in nursing at
      the same time the Hispanic population is experiencing serious health disparities.
      This descriptive, interpretive study explores strategies used by Hispanic nursing
      students to overcome obstacles from the perspectives of 13 currently enrolled
      students and recent graduates through focus groups and individual interviews.
      Successful students were highly motivated to succeed, while at the same time able
      to maintain strong cultural ties and family responsibilities, and used a strategy
      they called being cabezona(stubborn) in the face of numerous obstacles, including
      discrimination. Recommendations for nurse educators are presented, including the
      need for increased flexibility, mentoring support, and including curricular
      content about issues of privilege and oppression in nursing programs.

PMID- 20678082
TI  - Advantages and barriers to use of HeartCode BLS with voice advisory manikins for
      teaching nursing students.
AB  - Nursing students are expected to have competency in cardiopulmonary resuscitation
      (CPR): they may care for patients at risk for cardiac arrest and may encounter
      other emergency situations in their clinical practice. In the United States,
      students may take a basic life support (BLS) course prior to entering a nursing
      program or beginning their clinical experience. Extensive research has shown,
      however, that CPR knowledge and skills decline rapidly, within weeks of
      completing a course. The purpose of this paper is to describe advantages and
      barriers to the use of HeartCode BLS with voice advisory manikins for learning
      and practicing CPR psychomotor skills in a nursing education program.

PMID- 20678083
TI  - Cognitions and clinical performance: a comparison of high and low performing
      baccalaureate nursing students.
AB  - Studies to date have employed a variety of methods to elucidate the cognitive
      processes that underlie nursing actions in clinical situations. Most studies
      relied on clinical case scenarios rather than actual patient care situations, and
      did not supplement cognitive measures with quantitative measures of performance
      or physiologic outcomes of care. The present study employed a quasi-experimental
      design to describe and compare the verbal report data of baccalaureate nursing
      students who were assigned to high and low performing groups based on their
      ability to alter the physiological trajectory of the patient in a simulated task
      environment. Low performing participants observed many irrelevant cues and failed
      to perform vital actions in lieu of extraneous actions that were not directly
      related to the patient's condition. Higher performing students were better able
      to recognize salient symptoms suggestive of deterioration in the patient's
      condition and were more expeditious intervening to improve the patient's
      physiological status.

PMID- 20678084
TI  - Strengthening communication education in an undergraduate nursing curriculum.
AB  - As effective communication is an essential professional competency that is
      conceptualized and developed during undergraduate education, the purpose of this
      study was to investigate and reinforce the role of communication in the nursing
      undergraduate curriculum. Analysis of faculty and student focus group discussions
      revealed the benefit of purposefully structuring and explicitly articulating
      communication education throughout the undergraduate curriculum for increased
      accessibility and visibility of communication education, expanded ranges of
      available teaching and learning methods and resources, and strengthened ability
      to address undermining mixed communication messages. These findings have
      implications for how to specifically include communication education in a
      learning-centered undergraduate curriculum.

PMID- 20678085
TI  - Strategies to attract prospective students to the nursing profession.
AB  - The stagnation in the supply of nurses necessitates the adoption of contextually
      relevant strategies to attract recruits to the profession. The objective of this
      study was to understand how prospective candidates could be influenced to enter
      the profession, by determining what motivated current South African nurses to
      choose nursing as a profession. Support on entering the profession and employment
      security were rated as most important, while the influence of others and
      extrinsic rewards associated with nursing were perceived to be less important.
      Although private sector nurses and nurses who intended to change their employment
      sector were significantly more likely to rate employment security and extrinsic
      rewards highly, and public sector nurses and nurses from the more rural areas
      thought that the immediacy of support on entering the profession and intrinsic
      factors where more important, a homogenous approach to recruitment is possible.

PMID- 20678086
TI  - Molecular determination of selectivity of the site 3 modulator (BmK I) to sodium
      channels in the CNS: a clue to the importance of Nav1.6 in BmK I-induced neuronal
      hyperexcitability.
AB  - BmK I, a site-3-specific modulator of VGSCs (voltage-gated sodium channels) from
      the Chinese scorpion Buthus martensi Karsch, can induce spontaneous nociception
      and hyperalgesia and generate epileptiform responses in rats, which is attributed
      to the modulation of VGSCs in the neural system. However, which VGSC subtype is
      targeted by BmK I remains to be identified. Using two-electrode voltage-clamp
      recording, we studied the efficacy and selectivity of BmK I to three neuronal
      VGSCs co-expressed with the auxiliary beta1 subunit in Xenopus oocytes. Results
      revealed that BmK I induced a large increase in both transient and persistent
      currents in mNav1.6alpha/beta1 (where m indicates mouse), which correlated with a
      prominent reduction in the fast component of inactivating current. In comparison,
      BmK I-increased currents of rNav1.2alpha/beta1 (where r indicates rat) and
      rNav1.3alpha/beta1 were much smaller. The EC50 values of BmK I for
      rNav1.2alpha/beta1 (252+/-60 nM) and mNav1.6alpha/beta1 (214+/-30 nM) were
      similar and roughly half of that for rNav1.3alpha/beta1 (565+/-16 nM). Moreover,
      BmK I only accelerated the slow inactivation development and delay recovery of
      mNav1.6alpha/beta1 through binding to the channel in the open state. Residue-swap
      analysis verified that an acidic residue (e.g. Asp1602 in mNav1.6) within the
      domain IV S3-S4 extracellular loop of VGSCs was crucial for the selectivity and
      modulation pattern of BmK I. Our findings thus provide the molecular determinant
      explaining the divergent and intriguing behaviour of neuronal VGSCs in response
      to site-3-specific modulators, indicating that these subtypes play different
      roles in BmK I-induced hyperexcitablity in rat models.

PMID- 20678087
TI  - Plasma leptin, ghrelin and indexes of glucose and lipid metabolism in relation to
      the appearance of post-weaning oestrus in Mediterranean obese sows (Iberian pig).
AB  - Iberian pig is the most abundant Mediterranean swine. The lack of knowledge of
      the reproductive physiology of Mediterranean genotypes, with predisposition to
      obesity, led us to evaluate the influence of body condition and metabolic status
      at weaning on the resumption of follicular growth and the appearance of post
      weaning oestrus. Females failing to display post-weaning oestrus showed a high
      decrease in backfat mass during lactation; backfat depth at weaning was therefore
      lower than in sows becoming in oestrus. Females not bearing oestrus behaviour
      showed lower plasma leptin levels and higher ghrelin concentrations at weaning.
      Moreover, these sows evidenced dyslipidemic profile (increased triglyceridemia
      and cholesterolemia) and mobilization of fat reserves. Hence, changes in
      metabolic regulation of Iberian pigs may originate large effects on the
      resumption of ovulatory activity after weaning.

PMID- 20678088
TI  - Effects of repeated embryo collection on embryo recovery rate in fertile mares.
AB  - In mares, repeated embryo collection in successive oestrous cycles is necessary
      if a greater number of foals should be produced. We investigated effects of
      repeated embryo collection in fertile donor mares on embryo recovery rates. In
      addition, an influence of the individual mare and season on embryo recovery rates
      was studied. In nine mares, a total of 153 embryo collections were performed
      during 30 months (17 +/- 2.2 embryo collections per mare). The overall embryo
      recovery rate was 64% and did not differ among mares. Between successive embryo
      collection procedures, recovery rate varied significantly; however, no increase
      or decrease in the embryo recovery rate with increasing number of successive
      embryo collections was seen. In three mares, ovulation ceased from November to
      February. In the remaining six mares, embryo production was successfully
      continued throughout winter and no influence of the month on embryo recovery
      rates was detected.

PMID- 20678089
TI  - Response of thawed epididymal red deer spermatozoa to increasing concentrations
      of hydrogen peroxide, and importance of individual male variability.
AB  - Oxidative stress represents a challenge during sperm manipulation. We have tested
      the effect of increasing hydrogen peroxide (H(2)O(2)) levels on red deer
      spermatozoa after cryopreservation, and the role of male-to-male variation in
      that response. In a first experiment, eight thawed samples were submitted to 0,
      25, 50, 100 and 200 MUm H(2)O(2) for 2 h at 37  degrees C. Intracellular reactive
      oxygen species (H(2)DCFDA-CM) increased with H(2)O(2) concentration, but we only
      detected a decrease in sperm function (motility by CASA and chromatin damage by
      sperm chromatin structure assay) with 200 MUm. Lipoperoxidation assessed by the
      thiobarbituric acid reactive substance (TBARS) method increased slightly with 50
      MUm H(2)O(2) and above. In a second experiment, samples from seven males were
      submitted to 0 and 200 MUm H(2)O(2) for 2 h, triplicating the experiment within
      each male. Males differed at thawing and regarding their response to incubation
      and H(2)O(2) presence. We found that the kinematic parameters reflected male-to
      male variability, whereas the response of the different males was similar for
      lipid peroxidation and viability. A multiparametric analysis showed that males
      grouped differently if samples were assessed after thawing, after incubation
      without H(2)O(2) or after incubation with H(2)O(2) . Red deer spermatozoa are
      relatively resilient to H(2)O(2) after thawing, but it seems to be a great male
      to-male variability regarding the response to oxidative stress. The
      acknowledgement of this individual variability might improve the development of
      optimized sperm work protocols.

PMID- 20678090
TI  - Leprosy in transplant recipients: report of a case after liver transplantation
      and review of the literature.
AB  - Leprosy still is an important public health problem in several parts of the world
      including Brazil. Unlike the diseases caused by other mycobacteria, the incidence
      and clinical presentation of leprosy seems little affected in immunosuppressed
      patients. We report the first case, to our knowledge, of a liver transplant
      patient who developed multi-bacillary leprosy. The patient presented with papules
      and infiltrated plaques with loss of sensation suggestive of leprosy 3.5 years
      after living-related liver transplantation for autoimmune hepatitis. A skin
      biopsy showing non-caseating macrophagic granulomas, neuritis, and intact acid
      fast bacilli on Fite-Faraco stain, confirmed the diagnosis of borderline
      lepromatous leprosy. The donor of the liver did not show any evidence of leprosy.
      During follow-up, the patient presented 2 episodes of upgrading leprosy type I
      reactions, 1 mild before leprosy treatment, and 1 moderate 3 months after
      receiving standard multi-drug treatment (rifampicin, clofazimine, and dapsone).
      These reactions were accompanied by increase in liver function tests, especially
      of canalicular enzymes. This reaction occurred despite the patient's triple
      immunosuppression regimen. The moderate reaction was successfully treated with
      further immunosuppression (prednisone, 0.5 mg/kg). Currently, the patient is
      asymptomatic, off leprosy medication, with routine liver transplant follow-up.
      The dilemmas in diagnosis and management of such a case are discussed and the
      literature on leprosy in transplant recipients is reviewed.

PMID- 20678091
TI  - Annular lipoatrophy of the ankles: case report and review of the literature.
AB  - Annular lipoatrophy of the ankles also termed "annular atrophic connective tissue
      panniculitis of the ankles,""annular atrophy of the ankles," and "atrophic
      annular panniculitis of the ankles," is an inflammatory panniculitis that results
      in lipoatrophy with a predilection for the ankles. The disorder is seen
      predominantly in female children and demonstrates a mixed lobular panniculitis.
      It is likely a disorder of autoimmune etiology, supported by the findings of
      concurrent autoimmune disorders in several patients. We report a case of a 6-year
      old female with annular lipoatrophy of the ankles associated with Hashimoto
      thyroiditis and review the epidemiology and proposed pathogenesis of annular
      lipoatrophy of the ankles.

PMID- 20678092
TI  - Neonatal onset diffuse cutaneous mastocytosis: a case report and review of the
      literature.
AB  - Diffuse cutaneous mastocytosis is a rare variant of mast cell disease with
      widespread erythroderma, which is normally clinically apparent in early infancy.
      We report the case of a neonate who presented with diffuse erythrodermic rash and
      bullous lesions. Biopsy specimens showed a dense dermal infiltrate of mast cells.
      Serum histamine and tryptase levels were elevated. No somatic mutation of the c
      kit gene was found. Blistering ceased at 5 months of age, but atopic dermatitis
      appeared at 6 months and allergic workup revealed a high level of food-specific
      IgE. Herein, we describe the case and provide the first review of the literature
      on neonatal onset diffuse cutaneous mastocytosis to clarify the prognosis of this
      condition.

PMID- 20678093
TI  - Ulceroglandular tularemia.
AB  - A 14-year-old boy presented with fevers and nonspecific flu-like symptoms, as
      well as an enlarging ulcerated plaque involving the upper back, lymphadenopathy,
      and bilateral pulmonary nodules. Bacterial cultures of ulcer tissue grew
      Francisella tularensis on enriched chocolate agar plates. Making the diagnosis
      requires a high index of suspicion, and communication with the laboratory to
      successfully and safely culture these highly pathogenic bacteria is imperative.

PMID- 20678094
TI  - Bullous allergic contact dermatitis to pure henna in a 3-year-old girl.
AB  - Natural henna is known to have a very low allergic potential. We describe here an
      exceptional case of bullous contact dermatitis caused by pure henna.

PMID- 20678095
TI  - Fuchs syndrome associated with Mycoplasma pneumoniae (Stevens-Johnson syndrome
      without skin lesions).
AB  - Stevens-Johnson syndrome is a severe mucocutaneous disease following drugs or
      infections. We present a 7-year-old boy with mucous membrane lesions (stomatitis,
      conjunctivitis, and urethritis) but without skin lesions. The diagnosis of acute
      Mycoplasma pneumoniae infection strongly suggests a concomitant Fuchs syndrome.

PMID- 20678096
TI  - The safety and efficacy of tacrolimus ointment in pediatric patients with atopic
      dermatitis.
AB  - Atopic dermatitis (AD) is the most common skin disease in children, and its
      prevalence is increasing. It is a chronic disorder, characterized by intermittent
      flares and phases of remission. Treatment regimens often require multiple
      therapies. These can vary between patients, and in an individual patient,
      depending on the state of disease. The traditional treatment for AD flares is
      topical corticosteroids, which are fast acting and effective for relief of
      symptoms, but may cause adverse effects, including those resulting from systemic
      absorption, particularly in children. Topical calcineurin inhibitors (TCIs) are
      alternative treatments for AD. Tacrolimus ointment, a TCI, is approved for
      patients aged 2 years and older. Multiple studies have shown that tacrolimus is
      effective for short-term relief of symptoms in pediatric patients with AD. Long
      term trials have demonstrated that the effectiveness of tacrolimus is maintained
      for up to 4 years in children. Additional studies have revealed that long-term
      intermittent use of tacrolimus as part of maintenance therapy can prevent AD
      flares. Tacrolimus has a low potential for systemic accumulation, and analysis of
      long-term studies indicates that it has a good safety profile. Treatment with
      tacrolimus, alone or in combination with topical corticosteroids for acute
      flares, may be a useful option for long-term management of AD in pediatric
      patients.

PMID- 20678097
TI  - Buschke-Ollendorff syndrome with striking phenotypic variation resulting from a
      novel c.2203C>T nonsense mutation in LEMD3.
AB  - The Buschke-Ollendorff syndrome (BOS) (MIM 166700) is a rare autosomal dominant
      disorder with highly variable expression that consists of multiple cutaneous
      elastic nevi and osteopoikilosis. It may exhibit clinical variations, and in some
      patients either skin or bone lesions may be absent. Recently it has been
      demonstrated that the heterozygous loss of function in LEMD3 can result in
      osteopoikilosis, BOS, and melorheostosis. We have studied three generations in a
      family with BOS with a variable phenotype. The genetic analyses revealed a
      heterozygous c.2203C>T nonsense mutation at the LEMD3 locus. The mutation induces
      a change in the 735 arginine codon to a stop codon. This study shows the wide
      phenotypic variation in BOS and increases the repertory of mutations described to
      date in LEMD3.

PMID- 20678098
TI  - D-glufosinate as a male sterility agent for hybrid seed production.
AB  - A chemical male sterility system based on anther-localized conversion of the
      inactive D-enantiomer of the herbicide, glufosinate (2-amino-4-(methylphosphinyl)
      butanoate) to the phytotoxic L is described. Highly pure D-glufosinate was
      isolated in >98% enantiomeric excess from the racemate via fermentation with a
      strain of Escherichia coli expressing the PAT (L-glufosinate N-acetyl
      transferase) gene and purification of the unreacted D-enantiomer from the broth
      by ion exchange. A modified (F58K, M213S) form of the D-amino acid oxidase (DAAO)
      (EC 1.4.3.3) from Rhodosporidium toruloides was designed, tested in vitro and
      found to efficiently oxidize D-glufosinate to its 2-oxo derivative [2-oxo-4
      (methylphosphinyl)-butanoic acid]. Tobacco (Nicotiana tabacum) plants were
      transformed to express this modified oxidase under control of the TAP1 tapetum
      specific promoter. A number of the resultant transgenic lines exhibited complete
      male sterility that persisted for two or more weeks immediately following foliar
      treatment with 75 or 200 g/ha of D-glufosinate without exhibiting obvious
      phytotoxic symptoms or any measurable decline in female fertility. Similarly,
      plants containing the same construct and, additionally, a PAT gene expressed from
      a plastocyanin promoter exhibited significantly reduced male fertility and no
      reduction in female fertility following foliar application of racemic
      glufosinate. Thus, foliar application of d-glufosinate either purified or as the
      commercial herbicide, combined with anther expression of a modified DAAO promises
      to provide a cost-effective conditional chemical male sterility system with the
      characteristics necessary for practical F1 hybrid seed production.

PMID- 20678099
TI  - Effects of blood type and blood handling on feeding success, longevity and egg
      production in the body louse, Pediculus humanus humanus.
AB  - The effects of feeding different types of human blood to human body lice,
      Pediculus humanus humanus L. (Phthiraptera: Pediculidae), on feeding success,
      longevity and numbers of eggs laid were investigated using an artificial blood
      feeding system in the laboratory. No significant differences were found between
      lice fed on different human blood types for any of the parameters tested.
      However, when lice were fed on human blood of one blood type followed immediately
      by a different blood type, they took significantly smaller bloodmeals, their
      longevity was reduced and they laid fewer eggs per female than control lice that
      had been fed twice on the same human blood type. When lice were fed human blood
      that had been stored for 1-26 weeks, the quantity of blood taken, the proportion
      of lice that became fully engorged and lice longevity diminished gradually as the
      storage time of the blood increased, but there was no effect of storage time on
      the mean number of eggs laid per female. However, lice would not feed on 26-week
      old blood. The type of anticoagulant used had a significant effect on the
      proportion fed, longevity and number of eggs laid per female. Generally, EDTA
      (ethylenediaminetetraacetic acid)-treated blood reduced longevity and the number
      of eggs laid per female to a greater degree than heparinized or citrated blood.
      Lice fed on rabbit blood took significantly larger amounts of blood, lived longer
      and laid a higher mean number of eggs per female than lice fed on human blood.

PMID- 20678100
TI  - The diagnostic efficacy of cone beam CT for impacted teeth and associated
      features: a systematic review.
AB  - This review evaluates the evidence for the diagnostic efficacy of cone beam
      computed tomography (CBCT) for impacted teeth and associated features. PubMed,
      Embase and the Cochrane Library were searched using specific indexing terms and
      reference lists were hand searched. Two reviewers selected relevant publications
      on the basis of pre-determined inclusion criteria. Original studies were assessed
      using a modification of the quality assessment of diagnostic accuracy studies
      (QUADAS) tool. The literature search yielded 96 titles, of which 7 were included
      in the review. There was only limited evidence for diagnostic efficacy expressed
      as sensitivity, specificity and predictive values. Only two studies compared CBCT
      and panoramic radiographs with a valid reference method and presented the results
      in terms of percentage of correct diagnoses. This review reveals a need for
      studies that meet methodological standards for diagnostic efficacy of CBCT in the
      diagnosis of impacted teeth.

PMID- 20678101
TI  - Effects of laser-weld joint opening size on fatigue strength of Ti-6Al-4V
      structures with several diameters.
AB  - This study was conducted to evaluate the fatigue strength of Ti-6Al-4V laser
      welded joints with several diameters and joint openings. Sixty dumbbell rods were
      machined in Ti-6Al-4V alloy with central diameters of 1.5, 2.0 and 3.5 mm. The
      specimens were sectioned and then welded using two joint openings (0.0 and 0.6
      mm). The combination of variables created six groups, which when added to the
      intact groups made a total of nine groups (n = 10). Laser welding was executed as
      follows: 360 V per 8 ms (1.5 and 2.0 mm) and 380 V per 9 ms (3.5 mm) with focus
      and frequency regulated to zero. The joints were finished, polished and submitted
      to radiographic examination to be analysed visually for the presence of porosity.
      The specimens were then subjected to a mechanical cyclic test, and the number of
      cycles until failure was recorded. The fracture surface was examined with a
      scanning electron microscope (SEM). The Kruskal-Wallis test and Dunn test (alpha
      = 0.05) indicated that the number of cycles required for fracture was lower for
      all specimens with joint openings of 0.6 mm, and for 3.5-mm-diameter specimens
      with joint openings of 0.0 mm. The Spearman correlation coefficient (alpha =
      0.05) indicated that there was a negative correlation between the number of
      cycles and the presence of porosity. So, laser welding of Ti-6Al-4V structures
      with a thin diameter provides the best conditions for the juxtaposition of parts.
      Radiographic examination allows for the detection of internal voids in titanium
      joints.

PMID- 20678102
TI  - Cervical wear and occlusal wear from a periodontal perspective.
AB  - The aim of this study was to investigate whether cervical wear was associated
      with occlusal wear and clinical periodontal parameters in relatively older
      adults. A total of 30 patients, with multiple non-carious cervical lesions
      (NCCLs) and without a disease or condition that could cause heavy tooth wear,
      were included in the study. The periodontal parameters including plaque index,
      probing pocket depth, gingival recession (GR) and tooth mobility were obtained
      from 641 teeth of which 475 (74.1%) displayed NCCLs. The levels of cervical wear
      and occlusal wear were determined according to a tooth wear index. Premolars were
      more likely to develop cervical wear than canines, molars and incisors. Cervical
      wear was significantly associated with less plaque accumulation and the presence
      of shallow pockets. The teeth with advanced GR and without increased mobility
      were 2.583 and 1.715 times more likely to develop deeper cervical lesions,
      respectively. Age and the level of occlusal wear were not linked to the bucco
      lingual depth of cervical wear. In conclusion, the significant association of
      advanced cervical wear with the relatively healthy periodontal status suggested
      the role of abrasion and its possible combined action with erosion in the
      aetiology of NCCLs. The rate of GR and the lack of tooth mobility could
      constitute predisposing factors for the progression of cervical wear because the
      exposed root surfaces could be more susceptible to abrasion and/or erosion, and
      the non-mobile teeth resisting strongly against frictional forces, thus abrasive
      effects, could possibly develop cervical wear.

PMID- 20678103
TI  - Do computed tomography and magnetic resonance imaging add to temporomandibular
      joint disorder treatment? A systematic review of diagnostic efficacy.
AB  - A question frequently asked in the clinical practice of the professional who
      treats temporomandibular joint disorders (TMJD) is 'To make the cost/benefit
      ratio worthwhile for the patient, when should I request a temporomandibular joint
      (TMJ) computed tomography (CT) or magnetic resonance imaging (MRI)?' To evaluate
      the evidence of the efficacy of CT and MRI in the diagnosis of disc displacement,
      local inflammatory disorders, and arthrosis of the TMJ at therapeutic efficacy
      level, PubMed and Cochrane literature searches with specific indexing terms and a
      hand search were made. From the retrieved titles and abstracts, three examiners
      selected publications on the basis of predetermined inclusion and exclusion
      criteria. Data were extracted from the selected publications using a previously
      established protocol. Publications considered relevant were interpreted with the
      aid of the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool and
      publications that critically evaluate systematic reviews. The literature search
      yielded 584 titles and abstracts, of which 257 were selected and read in full
      text. One study was judged relevant. This study evaluated evidence of the
      efficacy of MRI in the diagnosis of disc position and configuration, disc
      perforation, joint effusion, and osseous and bone marrow changes in the
      temporomandibular joint, but no publication reported diagnostic thinking efficacy
      or therapeutic efficacy. In conclusion, the absence of studies on the therapeutic
      efficacy of MRI and CT on TMJD reinforces the need for investment in decision
      making studies; meanwhile, sectional imaging tests should be prescribed with
      caution, especially when health budgets are limited.

PMID- 20678104
TI  - Heat shock proteins (chaperones) in fish and shellfish and their potential role
      in relation to fish health: a review.
AB  - Heat shock proteins (HSPs), also known as stress proteins and extrinsic
      chaperones, are a suite of highly conserved proteins of varying molecular weight
      (c. 16-100 kDa) produced in all cellular organisms when they are exposed to
      stress. They develop following up-regulation of specific genes, whose
      transcription is mediated by the interaction of heat shock factors with heat
      shock elements in gene promoter regions. HSPs function as helper molecules or
      chaperones for all protein and lipid metabolic activities of the cell, and it is
      now recognized that the up-regulation in response to stress is universal to all
      cells and not restricted to heat stress. Thus, other stressors such as anoxia,
      ischaemia, toxins, protein degradation, hypoxia, acidosis and microbial damage
      will also lead to their up-regulation. They play a fundamental role in the
      regulation of normal protein synthesis within the cell. HSP families, such as
      HSP90 and HSP70, are critical to the folding and assembly of other cellular
      proteins and are also involved in regulation of kinetic partitioning between
      folding, translocation and aggregation within the cell. HSPs also have a wider
      role in relation to the function of the immune system, apoptosis and various
      facets of the inflammatory process. In aquatic animals, they have been shown to
      play an important role in health, in relation to the host response to
      environmental pollutants, to food toxins and in particular in the development of
      inflammation and the specific and non-specific immune responses to bacterial and
      viral infections in both finfish and shrimp. With the recent development of non
      traumatic methods for enhancing HSP levels in fish and shrimp populations via
      heat, via provision of exogenous HSPs or by oral or water administration of HSP
      stimulants, they have also, in addition to the health effects, been demonstrated
      to be valuable in contributing to reducing trauma and physical stress in relation
      to husbandry events such as transportation and vaccination.

PMID- 20678105
TI  - Aberrant left coronary artery, modified unroofing technique, and patch
      angioplasty.
AB  - BACKGROUND: We present a case of surgical correction of an aberrant left coronary
      artery arising from the right sinus of Valsalva. METHOD: In order to prevent
      stenosis and kinking of the neo-ostium, modified unroofing technique was combined
      with patch angioplasty. RESULTS: The clinical outcome was excellent with complete
      preservation of ventricular function, resolution of angina, and absence of aortic
      regurgitation. CONCLUSION: Addition of patch angioplasty to the unroofing
      technique improves outcome.

PMID- 20678106
TI  - Aortic complications of giant cell arteritis: a diagnostic and management
      dilemma.
AB  - We describe three giant cell aortitis patients who were operatively managed at
      our institution over the last seven years and review the recent relevant
      literature to highlight the specific features of the disease and the salient
      points of management in relation to the cardiac surgeon. 

PMID- 20678107
TI  - Aortic false lumen patency following the adventitial inversion technique for
      acute DeBakey type I aortic dissection.
AB  - BACKGROUND: We determined the beneficial effect of the adventitial inversion
      technique on reducing the patency rate of false lumens in acute aortic dissection
      (AAD) compared with the sandwich technique using Teflon felts. METHODS: Between
      2003 and 2008, 65 consecutive patients with DeBakey type I AAD underwent emergent
      surgery. To obliterate a false lumen, the sandwich technique was used in 35
      patients (group TS) before October 2006 and the adventitial inversion technique
      was used in 30 patients (group AIT) subsequent to October 2006. The false lumen
      patency was evaluated with computerized tomo-angiography (CTA). RESULTS: There
      were three operative deaths (AIT [n = 1]; TS [n = 2]). The operative morbidity
      rate was not different (AIT = 17.2%, TS = 21.2%). Follow-up was completed in 56
      patients (90.3%) with a mean duration of 12.2 +/- 4.9 months in the group AIT and
      31.8 +/- 19.8 months in the group TS. During the follow-up period, there were no
      deaths or aortic events. In 53 patients (AIT [n = 26]; TS [n = 27]), a
      postoperative one-year CTA was obtained and compared with that of immediate
      postoperative one. The patency rate in the immediate postoperative period was
      30.8% in group AIT and 63.0% in group TS (p = 0.019). On the follow-up CTA, it
      was 15.4% in group AIT and 48.1% in group TS (p = 0.018), respectively.
      CONCLUSIONS: The adventitial inversion technique can be performed safely and
      obliterate the false lumen more effectively than the sandwich technique. The
      adventitial inversion technique might decrease the incidence of reoperations
      related to aneurysmal changes and improve survival or event-free survival. 

PMID- 20678108
TI  - Management of prosthetic valves during ventricular assist device implantation.
AB  - BACKGROUND: An increasing number of patients requiring ventricular assist devices
      (VAD) have had previous valvular corrections, including valve repair and valve
      replacement with mechanical or bioprosthetic valves. The operative and peri
      operative management of these patients has been varied. METHODS: A retrospective
      study of VADs between January 1994 and June 2008 revealed 10 patients with
      previous prosthetic valves requiring management during and after VAD placement.
      Three patients were supported postcardiotomy after valve surgery. Two patients
      were supported due to cardiogenic shock postoperatively. Four patients were
      supported as a bridge to transplantation. One patient was supported as a
      destination therapy (DT). RESULTS: The mitral, valve was left untreated during
      VAD implantation regardless of valve repair or replacement. For aortic valves,
      the mechanical aortic valve was replaced with tissue valve in two patients and
      left untreated in one case. One patient had tricuspid valve repair previously and
      was left untouched. All patients with prosthetic valves in aortic, mitral and
      tricuspid position during VAD support received anticoagulation therapy. There
      were four deaths, and four went on to transplantation. One patient was weaned
      from VAD and discharged from the hospital. One patient received HeartMate I as
      DT. The most common causes of death were multisystem organ failure (MSOF) and
      sepsis. One patient had a thromboembolic event. CONCLUSIONS: The survival rate of
      60% is encouraging when compared to overall survival rates. The most common cause
      of death was MSOF. Patients with prosthetic valves may be safely managed during
      VAD support.

PMID- 20678109
TI  - Giant aneurysm after aortic coarctation: repair without circulatory arrest.
AB  - We describe the case of a 23-year-old patient presenting for redo aortic arch
      surgery because of recoarctation and poststenotic aneurysm formation after patch
      aortoplasty in infancy. Using the hemi-clamshell approach, the entire aortic arch
      was replaced and the supraaortic branches were reimplanted. The applied surgical
      technique using hypothermic extracorporeal circulation without cardiac arrest
      allowed an uninterrupted cerebral and spinal cord perfusion due to stepwise
      clamping of the aortic arch during reconstruction and resulted in an excellent
      neurologic outcome at six-month follow-up. 

PMID- 20678110
TI  - Aortic valve sparing procedure combined with sternal turnover for Marfan
      syndrome.

PMID- 20678111
TI  - Cardiac arrest with "pseudo-Brugada" ECG pattern in the setting of a coronary
      artery anomaly.
AB  - A 36-year-old Hispanic man with no prior cardiac history presented with chest
      pain and then ventricular fibrillation requiring defibrillation after a physical
      altercation. His ECG on presentation to the emergency room was suggestive of
      Brugada syndrome, which later normalized. Cardiac catheterization revealed
      anomalous origin of right coronary artery from the left coronary cusp (coursing
      between the pulmonary artery and the aorta) for which he underwent surgical
      reimplantation, and subsequent pharmacological challenge test did not provoke
      reappearance of a Brugada ECG pattern. A review of literature on Brugada syndrome
      and anomalous origin of the coronary arteries is presented. 

PMID- 20678112
TI  - Endovascular repair of an internal mammary artery to pulmonary artery acquired
      fistula.
AB  - We report on a rare occurrence of an acquired fistula between the left internal
      mammary artery and the pulmonary artery following coronary artery bypass
      grafting. Endovascular repair was employed using two polytetrafluoroethylene
      graft stents for sealing the communication sites, with good results after two
      years of follow-up.

PMID- 20678113
TI  - Cardiac hemangioma presenting with angina pectoris.
AB  - A 60-year-old female presented with a two-year history of exertional chest pain
      and progressive dyspnea. Resection of a cardiac hemangioma arising from the area
      of the bifurcation of the left anterior descending and circumflex coronary
      arteries resulted in complete resolution of her symptoms. The symptoms were
      likely caused by coronary steal.

PMID- 20678114
TI  - Total arch replacement with open stent-grafting for aneurysm of ductus arteriosus
      after surgery for patent ductus arteriosus.
AB  - A 73-year-old woman who had undergone ligation of patent ductus arteriosus (PDA)
      via a left thoracotomy 19 years earlier was admitted to our hospital under the
      diagnosis of thoracic aortic aneurysm. An enhanced computed tomography of the
      chest revealed a saccular aneurysm measuring a maximum diameter of 28 mm in the
      lesser curvature of the distal aortic arch; she was diagnosed with an aneurysm of
      ductus arteriosus after surgery for PDA. We performed total aortic arch
      replacement with open stent-grafting through median sternotomy. This approach
      enabled us to avoid the risk of dissecting adhesions around the aneurysm and
      clamping the aorta distal to the aneurysm. 

PMID- 20678115
TI  - A prospective observational study to compare conventional coronary artery bypass
      grafting surgery with off-pump coronary artery bypass grafting on basis of
      EuroSCORE.
AB  - INTRODUCTION: The use of cardiopulmonary bypass during coronary artery bypass
      grafting (CABG) surgery has been associated with substantial morbidity. Off-pump
      coronary bypass (OPCAB) surgery has become a widely used technique during recent
      years. EuroSCORE risk scale is the most rigorously evaluated scoring system in
      cardiac surgery to preoperatively quantify the risk of death and other serious
      postoperative complications. The aim of this prospective observational study was
      to compare the mortality and morbidity between OPCAB and conventional CABG in
      three major preoperative groups as assessed by EuroSCORE. MATERIAL AND METHOD:
      All consecutive patients undergoing isolated coronary artery bypass surgery
      between January 2003 and December 2004 at Wellington Hospital were included. In
      this period, 347 patients had conventional CABG and 254 patients had OPCAB. Data
      were prospectively collected according to Australasian Society of Cardiothoracic
      Surgeons' cardiac surgery data set. The preoperative additive EuroSCORE was
      computed in each patient and the patients were divided into three risk groups.
      Results of OPCAB and conventional CABG were compared on basis of EuroSCORE group.
      RESULTS: OPCAB surgery is preferably performed in patients with low-risk. OPCAB
      group had lesser number of grafts per patient. When adjusted with risk score,
      there was no statistically significant difference in mortality in any of the
      three groups. No significant difference was found for stroke, renal dysfunction,
      atrial fibrillation, re-exploration for bleeding, deep sternal wound infection,
      or pulmonary complications in either of three groups. However, inotropic
      requirement and requirements of blood products were less in OPCAB group.
      CONCLUSION: OPCAB does not offer any significant advantage in terms of mortality
      and morbidity over conventional CABG. 

PMID- 20678116
TI  - An increased dose of insulin detemir improves glycaemic control and reduces body
      weight of Japanese patients with diabetes.
AB  - AIMS: The aim of study was to evaluate the safety and efficacy of insulin detemir
      as a basal insulin switching from neutral protamine Hagedorn insulin (NPH) and
      insulin glargine in patients with diabetes on an intensive insulin therapy
      regimen. METHODS: This 6-month multicentre, prospective, treat-to-target
      [glycosylated haemoglobin (HbA(1c) ) less than 6.5%] trial included 92 people
      with diabetes (61 type 1, 29 type 2 and two unknown diabetes types). Detemir was
      administered first with fixed dose and injection times and then adapted to
      optimal dose after 3 months. RESULTS: Mean HbA(1c) (%) of all the subjects at
      months 4 to 6 of the study was improved compared with month 0 (7.34 +/- 0.87,
      7.28 +/- 0.88, 7.25 +/- 0.93 vs. 7.55 +/- 1.18; p < 0.05 paired t-test). However,
      significant improvement was seen only among the patients who had previously used
      NPH as a basal insulin. Twice-daily injection of basal insulin increased among
      people in the type 1 previously injected insulin glargine. Total insulin dose
      increased in the type 1 glargine group. The mean body weight change in the
      highest quartile body mass index (BMI) group was from 70.7 to 69.3 kg over the 6
      months. Quality of life (QoL) relating to the patients' glycaemic control tended
      to improve without a change in frequency of hypoglycaemia. CONCLUSIONS: The
      results suggest that insulin detemir has a greater effect on glycaemic control in
      subjects with poor glycaemic control using NPH; can reduce or maintain body
      weight in obese patients; and obtains perceptive stability for patients with
      unstable glycaemic control.

PMID- 20678117
TI  - Abundance and distribution of major groups of diazotrophic cyanobacteria and
      their potential contribution to N2 fixation in the tropical Atlantic Ocean.
AB  - The abundances of six N2-fixing cyanobacterial phylotypes were profiled at 22
      stations across the tropical Atlantic Ocean during June 2006, and used to model
      the contribution of the diazotrophs to N2 fixation. Diazotroph abundances were
      measured by targeting the nifH gene of Trichodesmium, unicellular groups A, B, C
      (UCYN-A, UCYN-B and UCYN-C), and diatom-cyanobiont symbioses Hemiaulus-Richelia,
      Rhizosolenia-Richelia and Chaetoceros-Calothrix. West to east gradients in
      temperature, salinity and nutrients [NO3- + NO2-, PO43-, Si(OH)4] showed the
      influence of the Amazon River plume and its effect on the distributions of the
      diazotrophs. Trichodesmium accounted for more than 93% of all nifH genes
      detected, dominated the warmer waters of the western Atlantic, and was the only
      diazotroph detected at the equatorial upwelling station. UCYN-A was the next most
      abundant (> 5% of all nifH genes) and dominated the cooler waters of the eastern
      Atlantic near the Cape Verde Islands. UCYN-C was found at a single depth (200 m)
      of high salinity and low temperature and nutrients, whereas UCYN-B cells were
      widespread but in very low abundance (6.1 * 101 +/- 4.6 * 102 gene copies l-1).
      The diatom-cyanobionts were observed primarily in the western Atlantic within or
      near the high Si(OH)4 input of the Amazon River plume. Overall, highest
      diazotroph abundances were observed at the surface and declined with depth,
      except for some subsurface peaks in Trichodesmium, UCYN-B and UCYN-A. Modelled
      contributions of Trichodesmium, UCYN-B and UCYN-A to total N2 fixation suggested
      that Trichodesmium had the largest input, except for the potential of UCYN-A at
      the Cape Verde Islands.

PMID- 20678118
TI  - Effects of acetyl-L-carnitine and oxfenicine on aorta stiffness in diabetic rats.
AB  - BACKGROUND: We compared the haemodynamic and metabolic effects of acetyl-L
      carnitine (one of the carnitine derivatives) and of oxfenicine (a carnitine
      palmitoyltransferase-1 inhibitor) in streptozotocin-induced diabetes in male
      Wistar rats. MATERIALS AND METHODS: Diabetes was induced by a single tail vein
      injection of 55mgkg(-1) streptozotocin. The diabetic animals daily treated with
      either acetyl-L-carnitine (150mgkg(-1) in drinking water) or oxfenicine (150mgkg(
      1) by oral gavage) for 8weeks,were compared with the untreated age-matched
      diabetic controls. Arterial wave reflection was derived using the impulse
      response function of the filtered aortic input impedance spectra. Thiobarbituric
      acid reactive substances (TBARS) measurement was used to estimate malondialdehyde
      (MDA) content. RESULTS: Oxfenicine, but not acetyl-L-carnitine, increased total
      peripheral resistance in diabetes, which paralleled its elevation in plasma
      levels of free fatty acids. By contrast, acetyl-L-carnitine, but not oxfenicine,
      resulted in a significant increase in wave transit time and a decrease in wave
      reflection factor, suggesting that acetyl-L-carnitine may attenuate the diabetes
      induced deterioration in systolic loading condition for the left ventricle. This
      was in parallel with its lowering of MDA/TBARS content in plasma and aortic walls
      in diabetes. Acetyl-L-carnitine therapy also prevented the diabetes-related
      cardiac hypertrophy, as evidenced by the reduction in ratio of the left
      ventricular weight to body weight. CONCLUSION:  Acetyl-L-carnitine, but not
      oxfenicine, attenuates aortic stiffening and cardiac hypertrophy, possibly
      through its decrease of lipid oxidation-derived MDA/TBARS in the rats with
      insulin deficiency.

PMID- 20678119
TI  - Item response modelling for clinical and laboratory testing.
AB  - BACKGROUND: Item response models using exponential modelling are more sensitive
      than classical linear methods for making predictions from psychological
      questionnaires. OBJECTIVE: To assess whether they can also be used for making
      predictions from quality of life questionnaires and clinical and laboratory
      diagnostic-tests. METHODS: Of 1000 anginal patients assessed for quality of life
      and 1350 patients assessed for peripheral vascular disease with diagnostic
      laboratory tests, items response modelling was applied using the Latent Trait
      Analysis program -2 of Uebersax. RESULTS: The 32 different response patterns
      obtained from test batteries of five items produced 32 different quality of life
      scores ranging from 3.4% to 74.5% and 32 different levels of peripheral vascular
      disease ranging from 9.9% to 83.5% with overall mean scores, by definition, of
      50%, whereas the classical method of analysis produced the discrete scores of
      only 0-5. The item response models produced an adequate fit for the data as
      demonstrated by chi-square goodness of fit values/degrees of freedom of 0.86 and
      0.64. CONCLUSIONS: 1 Quality of life assessments and diagnostic tests can be
      analysed through item response modelling, and provide more sensitivity than do
      classical linear models. 2 Item response modelling can change largely qualitative
      data into fairly accurate quantitative data, and can, even with limited sets of
      items, produce fairly accurate frequency distribution patterns of quality of
      life, severity of disease and other latent traits.

PMID- 20678120
TI  - Non-obese early onset diabetes mellitus in mutant cryptochrome1 transgenic mice.
AB  - BACKGROUND: An earlier report described that transgenic mice ubiquitously
      expressing cryptochrome1 (CRY1) with a mutation in cystein414 (CRY1-AP Tg mice)
      display diabetes mellitus in addition to anomalous circadian behaviours. This
      study examined characteristic aspects of symptoms to clarify the diabetes type
      and pathogenesis. MATERIALS AND METHODS: The body weights and blood glucose
      levels of CRY1-AP Tg mice were measured for 7weeks starting at 3weeks after
      birth. Glucose tolerance test for the mice of various ages and insulin tolerance
      test at 6weeks of age were conducted. Immunohistochemical analysis of islets was
      carried out for the mice of 19 and 40weeks of age. Basal and glucose-stimulated
      serum insulin levels of mice at 27weeks were also measured. RESULTS: Three-week
      old CRY1-AP Tg mice, which showed mild retardation in growth, already displayed
      glucose intolerance. Hyperglycaemia progressed with age, without accompanying
      insulin resistance. Insulin-stained areas in islets in CRY1-AP Tg mice were
      smaller than that in wild-type controls. Both basal and glucose-stimulated
      secretion of insulin decreased in CRY1-AP Tg mice. CONCLUSION: The symptoms of
      diabetes in CRY1-AP Tg mice turned out to be similar to those of maturity onset
      diabetes of the young (MODY) in humans in terms of early onset, non-obesity and
      primary dysfunction of beta cells. The CRY1-AP Tg mice might serve as an animal
      model of early onset insulin-secretory defect of diabetes.

PMID- 20678121
TI  - Salivary monitoring related to major surgery.
AB  - BACKGROUND: Prolonged surgical procedures involving stress, extended general
      anaesthesia and a long pre-surgical fasting period may have systemic effects such
      as alterations in saliva flow rate and composition. These may compromise the
      patient's electrolytes and fluid balance and cause dehydration, systemic stress
      and oxidative changes. PATIENTS AND METHODS: Saliva was collected prior and
      following surgery from 20 patients and 20 control subjects. The saliva samples
      were analysed for flow rates and levels of the following: calcium (Ca), magnesium
      (Mg), total protein, albumin and lactate dehydrogenase (LDH), total antioxidant
      status (TAS), uric acid (UA), superoxide dismutase (SOD), carbonyls, matrix
      metalloproteinases (MMPs) -2, -3 and -9 and heat shock proteins (HSPs) 70 and 90.
      RESULTS: Salivary levels of Ca, Mg, protein, albumin and LDH were higher in post
      surgical patients by 70% (P = 0.002), 88% (P = 0.0001), 120% (P = 0.13), 111% (P
      = 0.039) and 492% (P = 0.006) respectively than that in healthy controls.
      Salivary antioxidants in the surgical patients were higher while salivary
      carbonyls remained unchanged. Salivary TAS levels in pre- and post-surgical
      patients were higher by 63% (P = 0.001) and 85% (P = 0.0001) respectively, UA
      concentrations by 92% (P = 0.014) and 81% (P = 0.036) respectively and SOD values
      by 47% (P = 0.61) and 112% (P = 0.049) respectively. Salivary concentrations of
      MMP3 were higher in pre- and post-surgical patients by 23% (P = 0.067) and 30% (P
      = 0.044) respectively. CONCLUSIONS: Local salivary, oral and systemic-induced
      alterations should be prevented. Moreover, salivary collection and analysis may
      be a new, efficient tool in the monitoring of patients undergoing major surgery.
      Further related research is necessary.

PMID- 20678122
TI  - Chronic effect of right ventricular pacing on left ventricular rotational
      synchrony in patients with complete atrioventricular block.
AB  - BACKGROUND: Chronic effect of right ventricular (RV) pacing on left ventricular
      (LV) rotational synchrony is unknown. The aim of this study is to assess chronic
      effect of RV pacing on LV rotational synchrony using two-dimensional ultrasound
      speckle tracking imaging. METHODS AND RESULTS: Thirty-one patients who underwent
      dual-chamber pacemaker implantation for complete atrioventricular block, and age-
      and sex-matched 10 healthy controls were assessed. We divided our patients into
      RV apical (RVA, n = 16) and RV outflow tract (RVOT, n = 15) pacing groups. We
      compared echocardiographic parameters such as LV rotational synchrony between
      pacing groups and healthy control. We defined Q to peak rotation interval as the
      interval from the beginning of the Q-wave to the peak apical counter-clockwise or
      peak basal clockwise rotation. We calculated apical-basal rotation delay by
      subtracting basal Q to peak rotation interval from apical one as the
      representative of rotational synchronization. Apical-basal rotation delay of RVA
      pacing was significantly longer than that of healthy control (100 +/- 110 vs. -6
      +/- 15 ms, P = 0.002), while there was no statistically significant difference
      between RVOT pacing and healthy control (-3 +/- 99 vs. -6 +/- 15 ms, P = 0.919).
      CONCLUSIONS: LV rotation during RVOT pacing is synchronous at 15 months after
      pacemaker implantation, while RVA pacing provokes LV rotational dyssynchrony by
      inducing delayed apical rotation at 7 years after pacemaker implantation in
      patients with complete atrioventricular block.

PMID- 20678123
TI  - Difficulty of assessing response to resynchronization therapy by
      echocardiographic dyssynchrony indices: an everyday case.

PMID- 20678124
TI  - Deciphering the mysteries of crisscross heart by transthoracic echocardiography.
AB  - BACKGROUND: Accurate diagnosis of crisscross heart and its associated anomalies
      is important but problematic for cardiologists. This study aimed at identifying
      unique transthoracic echocardiographic features and common associated lesions of
      this complex condition. METHOD: Clinical and echocardiographic features of 10
      patients with crisscross anatomy were studied. Echocardiographic findings were
      verified by cardiac magnetic resonance imaging or surgical inspection. RESULTS:
      Crisscross anatomy (10 patients, age at diagnosis ranged from 1 month to 25
      years, five female) was identified in 0.076% of patients with congenital heart
      diseases from 1985 to 2006. All patients had cyanosis and 80% of them were
      underweight. Superior-inferior ventricles (SIV) and crossed ventricular inflow
      streams were seen in 90% and 100% of patients, respectively. All patients had
      abnormal ventriculo-arterial (VA) connections: five with transposition of great
      artery (L-type: n = 2; D-type: n = 3) and five with double outlet right
      ventricle. Commonly associated anomalies included ventricular septal defects
      (100%), right ventricular outflow tract obstruction (60%), atrioventricular
      valves straddling or overriding (50%), atrial septal defect (40%), and right
      ventricular hypoplasia (30%). Seven patients received cardiac surgery for the
      relief of cyanosis. CONCLUSIONS: SIV and crossed inflow streams are important
      diagnostic features for crisscross heart by transthoracic echocardiogram. The
      hemodynamic consequences of abnormal VA connections and associated defects impact
      surgical management.

PMID- 20678125
TI  - Effect of bisphosphonates on the progression of degenerative aortic stenosis.
AB  - Bisphosphonates appear to regulate mineralization in both bone and vasculature.
      Degenerative aortic stenosis (AS) is thought to be due to vascular calcification.
      We studied the effect of bisphosphonates on the progression of degenerative AS. A
      retrospective study was performed on patients >70 years, who had transthoracic
      echocardiograms (TTE) >1 year apart and an initial aortic valve area (AVA) of 0.6
      2.0 cm2. Patients were excluded if they had an ejection fraction <40%, other
      significant valvular or congenital heart disease, end-stage renal disease or
      heart transplant. The cohort was divided depending on the use of bisphosphonates.
      Data were obtained by review of the TTE reports. AVA, peak and mean aortic valve
      gradient (AVG), and the change between the studies were calculated. Of 4,270
      patients screened for AS, 76 patients fit study criteria with 8 in the
      bisphosphonate group and 68 in the nonbisphosphonate group. The period between
      the TTEs was 23 +/- 5 months in both the groups. AVA in the nonbisphosphonate
      group worsened by 0.2 cm2 and in the bisphosphonate group it improved by 0.1 cm2
      (P = 0.001 vs. nonbisphosphonate). The changes in peak and mean AVG between
      groups and compared to baseline were not significant. Bisphosphonates show
      promise for slowing the progression of degenerative AS.

PMID- 20678126
TI  - A case of an anomalous superior vena cava with anomalous pulmonary veins-when two
      wrongs do not make a right.
AB  - Intravenous agitated saline injection is useful in identifying right-to-left
      shunting at the atrial or intrapulmonary level. Anomalous systemic venous
      drainage to the left atrium is a rare but easily correctable cause of right-to
      left shunting which, if left undiagnosed, may have serious consequences,
      including meningitis and pyogenic brain abscesses. This case illustrates an
      unusual cause of right-to-left shunting and the utility of venous microbubble
      injection in its diagnosis.

PMID- 20678127
TI  - Pericardial effusion masquerading as an aortic dissection.
AB  - A 24-year-old woman with a history of recurrent syncope underwent an
      echocardiogram that was suspicious for an ascending aortic dissection. Cardiac
      magnetic resonance imaging was performed which showed no evidence of aortic
      dissection. However, it did demonstrate a pericardial effusion that extended to
      the aortic arch. This case shows how pericardial effusions can simulate the
      appearance of an aortic dissection because of its extension to the aortic arch.

PMID- 20678128
TI  - "Exercise-induced cardiac fatigue"--a review of the echocardiographic literature.
AB  - There is growing evidence to support the suggestion that prolonged strenuous
      exercise has a negative impact on left and right ventricular function during
      recovery. The main body of evidence covers a 20-year time window with many
      studies using transthoracic echocardiography to quantify cardiac function.
      Although studies have addressed different exercise modes and durations most work
      has been "field" based. During this time period echocardiographic instrumentation
      and techniques have evolved significantly and their application in the assessment
      of prolonged exercise has developed in tandem. The primary objective of this
      article is to provide reflective insight into the phenomenon of "exercise induced
      cardiac fatigue" by critically evaluating available literature in different
      competitive field studies or lab-based settings. We achieve this objective by
      introducing the empirical evidence in relation to echocardiographic modalities
      employed in developmental order including standard 2D, Doppler, tissue Doppler
      derived myocardial velocity and strain and myocardial speckle tracking
      echocardiography and by looking at different modes and duration of exercise. The
      insights provided by data based on each technique are critically reviewed,
      contradictory findings are explored and the potential for further work is
      identified. Furthermore the clinical implications and proposed mechanisms of
      "exercise-induced cardiac fatigue" are also explored.

PMID- 20678129
TI  - Transesophageal echocardiography for the diagnosis of pulmonary vein stenosis
      after catheter ablation of atrial fibrillation: a systematic review.
AB  - AIMS: Pulmonary vein (PV) stenosis is a potentially serious complication of
      catheter ablation of atrial fibrillation (AF). The optimal method for diagnosis
      of PV stenosis has not been established. We undertook a systematic review of the
      literature to investigate the diagnostic performance of transesophageal
      echocardiography (TEE) for the detection of PV stenosis after catheter ablation
      of AF. METHODS: We searched MEDLINE and EMBASE databases for studies evaluating
      the diagnostic performance of TEE for the detection of PV stenosis after catheter
      ablation of AF, compared to a reference standard of PV angiography, magnetic
      resonance imaging (MRI), or computed tomography (CT). Study quality was assessed
      using the QUADAS tool. RESULTS: A total of seven studies that included 344
      patients (1,344 PVs) met the selection criteria. Of these, three studies used PV
      angiography as the reference standard, while MRI and CT were used in two studies
      each. Compared to PV angiography, TEE had sensitivity between 82% and 100% and
      specificity between 98% and 100%. Compared to MRI, TEE sensitivity was 100% in
      both studies, while the specificity ranged between 98% and 99%. Compared to CT,
      TEE had sensitivity between 86% and 100% and specificity of 95%. Quality of the
      reviewed studies was somewhat limited by the retrospective design in most of the
      studies. CONCLUSIONS: TEE has a high sensitivity and specificity in detecting PV
      stenosis. Given its wide availability and favorable side effect profile, these
      data suggest that TEE is very useful tool for the diagnosis of PV stenosis after
      catheter ablation of AF.

PMID- 20678130
TI  - Primary spindle rhabdomyosarcoma of the breast in an adult female.

PMID- 20678131
TI  - Repair of bone defects around dental implants with bone morphogenetic
      protein/fibroblast growth factor-loaded porous calcium phosphate cement: a pilot
      study in a canine model.
AB  - OBJECTIVES: To study the effects of the bone morphogenetic protein-2 (BMP
      2)/fibroblast growth factor (bFGF)-loaded porous calcium phosphate cement (CPC)
      on the repair of bone defects around dental implants. MATERIAL AND METHODS:
      Thirty critical-sized bone defects in beagle dogs were repaired with engineered
      bone composed of autologous bone-marrow-derived mesenchymal stem cells (BMSCs),
      BMP-2, bFGF and CPC. Repairs were divided into six groups: BMSC/BMP-2/bFGF/CPC,
      BMSC/BMP-2/CPC, BMSC/bFGF/CPC, BMSC/CPC, CPC and no treatment. Polychrome
      sequential fluorescent labels were also performed post-operatively. Fluorescence
      histological examinations of undecalcified sections at post-operative week 12
      were performed to clarify changes in the new bone around the dental implants.
      RESULTS: The animals exhibited a perfect post-operative course, with none
      experiencing any infection. Undecalcified sections showed that new bone was
      actively formed in the BMP-2/bFGF group after 12 weeks. The bone mineralization
      apposition rate was better in the BMP-2/bFGF group than in the other groups
      (P<0.05). CONCLUSION: BMP-2 and bFGF together are more effective than either one
      alone in promoting the formation of new bone and may exert a synergistic activity
      at bone defects around dental implants.

PMID- 20678132
TI  - A prospective, controlled clinical trial evaluating the clinical and radiological
      outcome after 3 years of immediately placed implants in sockets exhibiting
      periapical pathology.
AB  - OBJECTIVES: the aim of the present study was to compare the clinical and
      radiological outcome of immediately placed implants in sockets with or without
      periapical pathology 3 years after implant placement. MATERIALS AND METHODS:
      twenty-nine patients with immediate implant placement were clinically and
      radiologically followed 3 years after implant placement (test group: 16 patients
      without periapical pathology, control group: 13 patients with periapical
      pathologies). Clinical (full-mouth bleeding score, full-mouth plaque score,
      clinical attachment level measurements and width of keratinized mucosa buccaly of
      the implant) and radiological parameters (vertical distance from the implant
      shoulder to the first bone-to-implant contact [IS-BIC]) were assessed. Both 95%
      confidence intervals, as well as results of statistical tests (one-sample, two
      sample and paired t-test) were provided. RESULTS: the implant survival rate was
      100% for all 29 implants after 3 years. The clinical and radiological parameters
      showed no statistically significant difference between the test and the control
      group at 3 years (two-sample t-test). The IS-BIC was between 1.54 +/- 0.88 mm
      (mesial, test) and 1.69 +/- 0.92 mm (distal, test). Between the 1- and 3-year
      visit the IS-BIC increased in both groups significantly on one side of the
      implant: 0.30 +/- 0.37 mm (mesial, test) and 0.33 +/- 0.43 mm (distal, control)
      (one-sample t-test). None of the 13 examined radiographs of implants immediately
      placed in sockets with periapical pathologies revealed retrograde peri
      implantitis after 3 years. CONCLUSION: it is concluded within the limitations of
      this study, that after careful debridement of the extraction socket, immediate
      placement of implants into sites with periapical pathologies can be a successful
      treatment modality for at least 3 years with no disadvantages in clinical and
      radiological parameters to immediately placed implants into healthy sockets.

PMID- 20678133
TI  - Expanding soft tissue with Osmed tissue expanders in the goat maxilla.
AB  - OBJECTIVES: soft tissue limitations are encountered in implant dentistry, due to
      the loss of alveolar bone. The aim of this study is to compare the outcome of
      soft tissue preparation using Osmed self-inflating soft tissue expanders with
      different in situ times in two implantation techniques. MATERIAL AND METHODS:
      Osmed self-inflating soft tissue expanders were implanted in goats using a tunnel
      approach and a flap approach. The animals were sacrificed after 1h (controls) and
      40 days (treated). A tattoo technique for stereographic measurements was used to
      look for soft tissue surface gain. Histological and histomorphometric analyses
      were performed to quantify and compare the changes in soft tissue volume and bone
      volume after 1h and 40 days of implantation. RESULTS: after 40 days, the
      expansion was visible and none of the goats had shown any inflammation. The space
      between the soft tissue and the bone was filled by the completely expanded
      expander and surrounding connective tissue. Between the test groups and the
      control groups, there was no histological difference in the structure of the soft
      tissue. CONCLUSIONS: all the tissue expanders expanded to their maximum size (2.8
      times) and were a reliable product for creating a space between soft tissue and
      bone. The overlying soft tissue remained in excellent shape. There was no
      difference in the soft tissue volume and the bone volume between the tunnel and
      the flap approach after 40 days.

PMID- 20678134
TI  - The effect of water pyrolysis on the removal torque of titanium implant inserted
      in rabbit tibias.
AB  - OBJECTIVE: The aim of this study is to examine the effect of oxidation with water
      pyrolysis (OWP) method on titanium (Ti) implants by comparing the bonding
      strength between bone and Ti implants that were inserted in the proximal tibia
      metaphysic of a rabbit for 12 weeks. The removal torque was measured to evaluate
      the bonding strength for different Ti implants with and without the OWP method.
      MATERIAL AND METHODS: Nine sets of threaded Ti implants (ASTM grade 2) of
      diameter 3.75 mm and length 5 mm were prepared for the experiment. Each set was
      composed of four specimens; one was machine-prepared (group D) and the other
      three were threaded followed by the OWP method at 300 degrees C (group A), 600
      degrees C (group B), and 800 degrees C (group C) for 10 min, respectively. Each
      set was used for each adult rabbit. To eliminate the effect of the sites or the
      legs, each rabbit received all four implants, two in the left and two in the
      right leg, inserted in the proximal tibia metaphyses of the left leg, using a
      fixed block randomization. After 12 weeks, removal torque tests were carried out.
      RESULTS: The mean removal torque for the control group D was 16.19 N cm, while
      the mean removal torque values for the OWP groups A, B, and C were 26.75, 31.51,
      and 41.05 N cm, respectively. The removal torques obtained from the OWP groups B
      and C (showing the rutile oxide structure) were significantly greater than that
      for the control group by Bonferroni's-corrected Wilcoxon's signed-rank test
      (P<0.05). CONCLUSION: The strongest bonding between bone and group C (OWP method
      at 800 degrees C) was confirmed by the comparison of removal torques.

PMID- 20678135
TI  - Subcutaneous reactions and degradation characteristics of collagenous and
      noncollagenous membranes in a macaque model.
AB  - BACKGROUND: collagenous and noncollagenous membranes have been investigated in
      many animal systems but their effects in the macaque model are unknown.
      OBJECTIVE: to determine subcutaneous cellular reactions and degradation
      characteristics following implantation of collagenous and noncollagenous
      membranes in a macaque model. METHODS: six adult male Macaca fascicularis, aged
      above 7 years, were used. Six commercially available collagenous (Bio-Gide [BG],
      Tissue Fleece [TFL] TissueFoil E forte [TFO], Lycoll [LC], Surgicoll [SG] and
      Tutodent [TU]) and two noncollagenous (Tabotamp [TA] and Gelita-Tampon [GT])
      membranes (size 2 * 2 cm each) were implanted in unconnected subcutaneous pouches
      in the monkey's back and wounds were allowed to heal by primary intention. The
      total sample size for each membrane was six. Two monkeys were sacrificed for each
      experimental period of 4, 14 and 28 days. Explanted specimens were prepared for
      histologic and histomorphometric analysis. Digitized images of implant sites were
      systematically sampled using an Image Analyzer with a grid containing 35
      intersection points. Four parameters were quantified: membrane degradation,
      foreign body reaction, tissue organization and vascularization. RESULTS:
      biodegradation rate and vascularization scored higher in collagenous than in
      noncollagenous membranes. Except for TFL and TU, the remaining six membranes
      showed a moderately intense foreign body reaction at week 2. Tissue organization
      was initiated early in four out of six collagenous (TFL>LC>SG>TFO>BG>TU) compared
      with one of two noncollagenous (TA>GT) membranes. CONCLUSIONS: the results
      suggest that differences in membrane structure and composition underlie their
      different cellular reactions and degradation characteristics.

PMID- 20678136
TI  - Vertical augmentation with interpositional blocks of anorganic bovine bone vs. 7
      mm-long implants in posterior mandibles: 1-year results of a randomized clinical
      trial.
AB  - OBJECTIVES: To evaluate whether 7-mm-long implants could be an alternative to
      longer implants placed in vertically augmented posterior mandibles. MATERIALS AND
      METHODS: Sixty patients with posterior mandibular edentulism with 7-8 mm bone
      height above the mandibular canal were randomized to either vertical augmentation
      with anorganic bovine bone blocks and delayed 5-month placement of >=10 mm
      implants or to receive 7-mm-long implants. Four months after implant placement,
      provisional prostheses were delivered, replaced after 4 months, by definitive
      prostheses. The outcome measures were prosthesis and implant failures, any
      complications and peri-implant marginal bone levels. All patients were followed
      to 1 year after loading. RESULTS: One patient dropped out from the short implant
      group. In two augmented mandibles, there was not sufficient bone to place 10-mm
      long implants possibly because the blocks had broken apart during insertion. One
      prosthesis could not be placed when planned in the 7 mm group vs. three
      prostheses in the augmented group, because of early failure of one implant in
      each patient. Four complications (wound dehiscence) occurred during graft healing
      in the augmented group vs. none in the 7 mm group. No complications occurred
      after implant placement. These differences were not statistically significant.
      One year after loading, patients of both groups lost an average of 1 mm of peri
      implant bone. There no statistically significant differences in bone loss between
      groups. CONCLUSIONS: When residual bone height over the mandibular canal is
      between 7 and 8 mm, 7 mm short implants might be a preferable choice than
      vertical augmentation, reducing the chair time, expenses and morbidity. These 1
      year preliminary results need to be confirmed by follow-up of at least 5 years.

PMID- 20678137
TI  - Occurrence of common and rare delta-globin gene defects in two multiethnic
      populations: thirteen new mutations and the significance of delta-globin gene
      defects in beta-thalassemia diagnostics.
AB  - INTRODUCTION: The aim of this review is to study the frequency of common and the
      occurrence of rare and novel mutations of the delta-globin gene and of Hb Lepore
      defects that might interfere with thalassemia diagnostics and to report the
      rationale of HbA2 estimation in the presence of delta- or alpha-gene mutations.
      METHODS: A total of 135 cases suspected to have a delta-globin gene defect
      collected in a diagnostic center in the USA and in a reference laboratory in the
      Netherlands were characterized by molecular analysis. RESULTS: Hb B2 was found at
      a frequency of at least 0.5% in the USA and 0.87% in the Netherlands. Known
      variants such as Hb A2-Babinga, Hb A2-Sphakia, Hb A2-Fitzroy, Hb A2-Flatbush, Hb
      A2-NYU, Hb A2-Grovetown, HbA2-Yialousa, Hb A2-Indonesia and several delta
      thalassemia mutations were found together with 13 new mutations and two new
      polymorphisms, while Hb Lepores were regularly observed. CONCLUSION: HbA2
      mutations either structurally stable and visible or undetectable because of a
      thalassemia effect or instability are clinically asymptomatic but may compromise
      the diagnosis of beta-thalassemia minor. Stable mutations result in two HbA2
      fractions of about half of the expected value. Expression defects are
      undetectable as a protein fraction but reduce the amount of HbA2 by half.

PMID- 20678138
TI  - A zygote could be a human: a defence of conceptionism against fission arguments.
AB  - In this paper I defend the view that a zygote is a human from the fission
      objection that is widely thought to be decisive against the view. I do so,
      drawing upon a recent discussion of this issue by John Burgess, by explaining in
      detail the metaphysical position the proponent of the view should adopt in order
      to rebut the objection.

PMID- 20678139
TI  - Inference from habitat-selection analysis depends on foraging strategies.
AB  - 1. Several methods have been developed to assess habitat selection, most of which
      are based on a comparison between habitat attributes in used vs. unused or random
      locations, such as the popular resource selection functions (RSFs). Spatial
      evaluation of residency time has been recently proposed as a promising avenue for
      studying habitat selection. Residency-time analyses assume a positive
      relationship between residency time within habitat patches and selection. We
      demonstrate that RSF and residency-time analyses provide different information
      about the process of habitat selection. Further, we show how the consideration of
      switching rate between habitat patches (interpatch movements) together with
      residency-time analysis can reveal habitat-selection strategies. 2. Spatially
      explicit, individual-based modelling was used to simulate foragers displaying one
      of six foraging strategies in a heterogeneous environment. The strategies
      combined one of three patch-departure rules (fixed-quitting-harvest-rate, fixed
      time and fixed-amount strategy), together with one of two interpatch-movement
      rules (random or biased). Habitat selection of simulated foragers was then
      assessed using RSF, residency-time and interpatch-movement analyses. 3. Our
      simulations showed that RSFs and residency times are not always equivalent. When
      foragers move in a non-random manner and do not increase residency time in richer
      patches, residency-time analysis can provide misleading assessments of habitat
      selection. This is because the overall time spent in the various patch types not
      only depends on residency times, but also on interpatch-movement decisions. 4. We
      suggest that RSFs provide the outcome of the entire selection process, whereas
      residency-time and interpatch-movement analyses can be used in combination to
      reveal the mechanisms behind the selection process. 5. We showed that there is a
      risk in using residency-time analysis alone to infer habitat selection. Residency
      time analyses, however, may enlighten the mechanisms of habitat selection by
      revealing central components of resource-use strategies. Given that management
      decisions are often based on resource-selection analyses, the evaluation of
      resource-use strategies can be key information for the development of efficient
      habitat-management strategies. Combining RSF, residency-time and interpatch
      movement analyses is a simple and efficient way to gain a more comprehensive
      understanding of habitat selection.

PMID- 20678140
TI  - Mapping the knowledge utilization field in nursing from 1945 to 2004: a
      bibliometric analysis.
AB  - BACKGROUND: The field of knowledge utilization has been hampered by several
      issues including: the synonymous use of multiple terms with little attempt at
      definition precision; an overexamination of knowledge utilization as product,
      rather than a process; and a lack of progress to cross disciplinary boundaries to
      advance knowledge development. In order to address the challenges and current
      knowledge gaps in the knowledge utilization field in nursing, a comprehensive
      picture of the current state of the field is required. METHODS: Bibliometric
      analyses were used to map knowledge utilization literature in nursing as an
      international field of study, and to identify the structure of its scientific
      community. FINDINGS: Analyses of bibliographic data for 433 articles from the
      period 1945-2004 demonstrated three trends: (1) there has been significant recent
      growth and interest in this field, (2) the structure of the scientific knowledge
      utilization community is evolving, and (3) the Web of Science does not index the
      majority of journals where this literature is published. CONCLUSIONS: In order to
      enhance the accessibility and profile of this literature, and nursing's
      scientific literature at large, we encourage the International Academy of Nursing
      Editors to work collaboratively to increase the number of journals indexed in the
      Web of Science.

PMID- 20678141
TI  - Transport and variability of fecal bacteria in carbonate conglomerate aquifers.
AB  - Clastic sedimentary rocks are generally considered non-karstifiable and thus less
      vulnerable to pathogen contamination than karst aquifers. However, dissolution
      phenomena have been observed in clastic carbonate conglomerates of the Subalpine
      Molasse zone of the northern Alps and other regions of Europe, indicating
      karstification and high vulnerability, which is currently not considered for
      source protection zoning. Therefore, a research program was established at the
      Hochgrat site (Austria/Germany), as a demonstration that karst-like
      characteristics, flow behavior, and high vulnerability to microbial contamination
      are possible in this type of aquifer. The study included geomorphologic mapping,
      comparative multi-tracer tests with fluorescent dyes and bacteria-sized
      fluorescent microspheres, and analyses of fecal indicator bacteria (FIB) in
      spring waters during different seasons. Results demonstrate that (1) flow
      velocities in carbonate conglomerates are similar as in typical karst aquifers,
      often exceeding 100 m/h; (2) microbial contaminants are rapidly transported
      toward springs; and (3) the magnitude and seasonal pattern of FIB variability
      depends on the land use in the spring catchment and its altitude. Different
      groundwater protection strategies that currently applied are consequently
      required in regions formed by karstified carbonatic clastic rocks, taking into
      account their high degree of heterogeneity and vulnerability.

PMID- 20678142
TI  - "Simulating piecewise-linear surface water and groundwater interactions with
      MODFLOW," by W.J. Zaadnoordijk, September-October 2009, v. 47, no. 5: 723-726.

PMID- 20678143
TI  - Water to people, or people to water?

PMID- 20678144
TI  - "Characterizing hydraulic conductivity with the direct-push permeameter," by
      James J. Butler Jr., Peter Dietrich, Volker Wittig, and Tom Christy, July-August
      2007, v. 45, no. 4:409-419.

PMID- 20678145
TI  - Variations on transcriptional and post-transcriptional processes in bacteria.

PMID- 20678146
TI  - Allocating monitoring effort in the face of unknown unknowns.
AB  - There is a growing view that to make efficient use of resources, ecological
      monitoring should be hypothesis-driven and targeted to address specific
      management questions. 'Targeted' monitoring has been contrasted with other
      approaches in which a range of quantities are monitored in case they exhibit an
      alarming trend or provide ad hoc ecological insights. The second form of
      monitoring, described as surveillance, has been criticized because it does not
      usually aim to discern between competing hypotheses, and its benefits are harder
      to identify a priori. The alternative view is that the existence of surveillance
      data may enable rapid corroboration of emerging hypotheses or help to detect
      important 'unknown unknowns' that, if undetected, could lead to catastrophic
      outcomes or missed opportunities. We derive a model to evaluate and compare the
      efficiency of investments in surveillance and targeted monitoring. We find that a
      decision to invest in surveillance monitoring may be defensible if: (1) the
      surveillance design is more likely to discover or corroborate previously unknown
      phenomena than a targeted design and (2) the expected benefits (or avoided costs)
      arising from discovery are substantially higher than those arising from a well
      planned targeted design. Our examination highlights the importance of being
      explicit about the objectives, costs and expected benefits of monitoring in a
      decision analytic framework.

PMID- 20678147
TI  - Malignant melanoma during treatment with fumaric acid esters - coincidence or
      treatment-related?
AB  - Psoriasis is today generally considered a systemic disease. Systemic therapies
      are used frequently. In Germany fumaric acid esters - FAE (Fumaderm((r)) ) - are
      employed in more than 50 % of the patients requiring such therapy. We report for
      the first time the development of melanoma in two patients during their treatment
      with FAE. The logical question is - are the tumors coincidental or might they be
      treatment-related? Further investigations of pathways and immunologic effects as
      well as careful reports of side effects are necessary to estimate the risks of
      malignancy of FAE.

PMID- 20678148
TI  - Omalizumab therapy in atopic dermatitis: depletion of IgE does not improve the
      clinical course - a randomized, placebo-controlled and double blind pilot study.
AB  - BACKGROUND: Our understanding of the pathogenic role of IgE in atopic dermatitis
      is incomplete. We asked whether blocking free IgE would alter the course of the
      disease. PATIENTS AND METHODS: We administered either omalizumab, a humanized
      monoclonal mouse antibody against IgE, or placebo subcutaneously for 16 weeks to
      20 atopic dermatitis patients and measured immunological and clinical disease
      parameters. RESULTS: Omalizumab (I) reduced free serum IgE, (II) lowered surface
      IgE and FcERI expression on different peripheral blood mononuclear cells, (III)
      reduced the saturation of FcERI with IgE, (IV) increased the number of free FcERI
      and (V) lowered the number of IgE+, but not of FcERI+ cells in skin. The in vivo
      relevance of these results is evidenced by the increase in the threshold allergen
      concentration required to give a type I hypersensitivity reaction in the titrated
      skin test. While not significantly altering the clinical disease parameters,
      omalizumab treatment led to an improvement of the atopy patch test results in
      single patients, i.e. an eczematous reaction upon epicutaneous allergen
      challenge. CONCLUSIONS: The interference with immediate and delayed type skin
      tests may imply that a therapeutic benefit of omalizumab treatment, if present at
      all, would be seen in patients with acute rather than chronic forms of the
      disease.

PMID- 20678149
TI  - Use of antimalarials in dermatology.
AB  - The antimalarials chloroquine and hydroxychloroquine have been used for the
      treatment of inflammatory diseases for more than 60 years. Even today new
      indications evolve due to the complex mode of action of these compounds. Due to
      the fear of side effects, especially irreversible retinopathy, their use is often
      limited. These side-effects, however, are a consequence of excessive daily
      dosages. An effective, safe therapy needs correct dosing, i. e. adherence to
      maximal daily dosages of 3.5(-4) mg chloroquine or 6(-6.5) mg hydroxychloroquine
      per kilogram ideal body weight. If the actual body weight is lower than the ideal
      body weight, this actual weight is used for the calculation of the dosage.
      Observing these limits allows a rather safe therapy of the diseases like lupus
      erythematosus, REM syndrome, porphyria cutanea tarda (2 * 125 mg
      chloroquine/week), cutaneous sarcoidosis and dermatomyositis. If standard
      therapies fail, then antimalarials can be tried to treat Sjogren syndrome,
      granuloma annulare or erosive lichen planus. If therapy fails, either can be
      combined with quinacrine to increase their effectiveness. Chloroquine and
      hydroxychloroquine are indispensable and well-tolerated essential drugs in
      dermatology and especially suited as part of a combination scheme, for example
      with corticosteroids, as they act synergistically and reduce side-effects.

PMID- 20678150
TI  - Cornu cutaneum-like HPV 45 positive subungual squamous cell carcinoma.
AB  - A cornu cutaneum (cutaneous horn) is a clinical descriptive term referring to a
      skin tumor having the appearance of an animal horn. Histopathologically, the
      lesion may be associated with several different tumors. Along with some benign
      entities such as warts or seborrheic keratoses, a cutaneous horn may be also
      associated with actinic keratoses, Bowen disease and squamous cell carcinoma.
      When an underlying malignancy is present, the entire tumor must be removed with
      careful control of margins. We report a case of a 68-year-old man with a cornu
      cutaneum-like HPV 45 positive sub-ungual squamous cell carcinoma on the left
      second toe.

PMID- 20678151
TI  - Mastocytosis - an update.
AB  - Mastocytosis (MC) encompasses a range of disorders characterized by a clonal,
      pathological accumulation of mast cells having a somatic activating mutation of
      the tyrosine kinase receptor Kit (exon 17, codon 816; D816V) in more than 90 % of
      adult patients. The mutation is much less common in children. Skin and bone
      marrow are most often affected. Symptoms and clinical course are very
      heterogeneous due to a variable degree of local or systemic mediator release or
      organ dysfunction as a result of mast cell infiltrates. Pruritus, wheals,
      flushing and gastrointestinal symptoms are often reported. The majority of
      pediatric patients experience spontaneous remission of MC. Adults usually have
      chronic disease, rarely transforming into an aggressive or lethal type. Indolent
      systemic MC with involvement of skin and bone is the most common type. In MC the
      risk for anaphylactic reactions following an insect sting (and other causes of
      mast cell activation) is increased significantly. Diagnostic hallmarks are
      biopsies from skin and bone marrow using tryptase antibodies for staining as well
      as serum tryptase levels. At present a curative treatment for MC is not
      available. Systemic histamine H(1) receptor antagonists are widely used.
      Aggressive types of MC respond partially to IFN-alpha or cladribine. A variety of
      receptor tyrosine kinase inhibitors is still under critical evaluation for
      systemic treatment of MC. After introduction of the WHO classification for MC and
      the development a German MC guideline, as well as the foundation of national and
      international competence networks for MC, a significantly improved quality of
      medical care for MC patients can be expected for the future.

PMID- 20678152
TI  - Pathogenesis of tinea.
AB  - Dermatophytes are hyphomycetes that can degrade keratin. This puts them in a
      position to cause infections of the keratin-containing superficial skin. The
      resulting clinical picture is called tinea. The pathogenesis and course of tinea
      is decisively determined by pathogen-related factors and by the defense
      mechanisms of the host. An infection starts with an adherence of fungal
      propagules, followed by the formation of hyphae that can spread within the
      tissue. This process is accompanied by a release of fungal enzymes and other
      pathogenic factors. Next keratinocytes are activated, the epidermal barrier is
      destroyed, epidermal proliferation is enhanced and defensins are expressed within
      the epidermis. In addition, innate and specific immune responses are initiated,
      involving neutrophilic granulocytes, macrophages, antibodies and T cells. The
      cellular mechanisms are thought to be crucial for healing. Special conditions
      apply to nail infections, because within nail plates the fungi are not accessible
      to effective defense mechanisms, as well as to infections of hair follicles that
      contain specific concentrations of steroid hormones. Dermatophytes that penetrate
      into the dermis can cause granulomatous inflammatory reactions and systemic
      immune reactions are supposed to be a trigger of so-called id reactions.

PMID- 20678153
TI  - The role of oxidative stress in renovascular hypertension.
AB  - 1. There is mounting evidence that increased oxidative stress and sympathetic
      nerve activity play important roles in renovascular hypertension. In the present
      review, we focus on the importance of oxidative stress in two distinct
      populations of neurons involved with cardiovascular regulation: those of the
      rostral ventrolateral medulla (RVLM) and those of the paraventricular nucleus of
      the hypothalamus (PVN) in the maintenance of sympathoexcitation and hypertension
      in two kidney-one clip (2K1C) hypertensive rats. Furthermore, the role of
      oxidative stress in the clipped kidney is also discussed. 2. In the studies
      reviewed in this article, it was found that hypertension and renal
      sympathoexcitation in 2K1C rats were associated with an increase in Angiotensin
      II type one receptor (AT(1) ) expression and in oxidative markers within the
      RVLM, PVN and in the clipped kidneys of 2K1C rats. Furthermore, acute or chronic
      anti-oxidant treatment decreased blood pressure and sympathetic activity, and
      improved the baroreflex control of heart rate and renal sympathetic nerve
      activity in 2K1C rats. Tempol or vitamin C administration in the RVLM, PVN or
      systemically all reduced blood pressure and renal sympathetic activity.
      Cardiovascular improvement in response to chronic anti-oxidant treatment was
      associated with a downregulation of AT(1) receptors, as well as oxidative markers
      in the central nuclei and clipped kidney. 3. The data discussed in the present
      review support the idea that an increase in oxidative stress within the RVLM, PVN
      and in the ischaemic kidney plays a major role in the maintenance of
      sympathoexcitation and hypertension in 2K1C rats.

PMID- 20678154
TI  - Inhibition of the renal renin-angiotensin system and renoprotection by
      pitavastatin in type1 diabetes.
AB  - 1. The aim of the present study was to investigate whether or not pitavastatin
      ameliorates diabetic nephropathy and if inhibition of the rennin-angiotensin
      aldosterone system (RAAS) is associated with any renoprotective effects.
      Pitavastatin (10mg/ kg/day) and/or spironolactone (100mg/kg/day) were given by
      gavage for 3weeks to uninephrectomized rats with streptozotocin-induced diabetes.
      2. Pitavastatin or spironolactone significantly reduced proteinuria and collagen
      deposition, and normalized creatinine clearance, serum creatinine levels and
      blood urea nitrogen concentrations. 3. Reverse transcription polymerase chain
      reaction analysis showed that the renal expression of collagenI, transforming
      growth factor-beta and monocyte chemoattractant-1 were increased in diabetic rats
      and reduced by the pitavastatin and/or spironolactone treatment. 4. These agents
      also decreased angiotensin converting enzyme expression and aldosterone
      concentrations in the renal homogenate, but had no effect on blood glucose,
      haemoglobinA(1c) , and plasma total cholesterol, Na(+) , K(+) , aldosterone and
      NOx levels, or on systolic blood pressure measured by the tail-cuff method.
      Interestingly, cotreatment with pitavastatin and spironolactone did not result in
      additional normalization. 5. These results suggest that pitavastatin shows
      renoprotective effects against diabetic nephropathy mediated in part by
      inhibition of the renal RAAS, including the suppression of angiotensin-converting
      enzyme expression and aldosterone production.

PMID- 20678155
TI  - Evaluation of a new oil adjuvant for use in peptide-based cancer vaccination.
AB  - Vaccine therapies are increasingly being used for the treatment of various
      diseases, and the antigen molecules themselves are being expanded from whole
      microorganisms to fine molecules such as peptides. Accordingly, there is a need
      for new adjuvants to support these new applications. In this paper, we used
      pharmaceutical grade mineral oil and sorbitan monooleate to develop a new oil
      adjuvant formula, NH(2) , and investigated its effects on peptide vaccination at
      both the pre-clinical and clinical levels. The adjuvant effect of NH(2) on
      peptide-induced cellular immunity in mice was superior to that of Montanide
      ISA51VG, a commercially available incomplete Freund's adjuvant for clinical use,
      although no significant difference was observed between the two adjuvants on
      peptide-induced humoral immunity. The adjuvant effects of NH(2) were also
      confirmed in a Phase-I clinical trial of peptide vaccines for patients with
      advanced cancers. These results suggest that NH(2) is a suitable adjuvant for
      peptide vaccination, particularly for cancer vaccines (Phase-I clinical trial of
      pan-HLA type personalized peptide vaccine for advanced cancer patients, UMIN
      clinical trial registry number: UMIN 000000619).

PMID- 20678156
TI  - Early reduction of glucose uptake after cisplatin treatment is a marker of
      cisplatin sensitivity in ovarian cancer.
AB  - Cisplatin is an effective chemotherapeutic agent for ovarian cancer, but the
      sensitivity of cancers differs in individual cases. Because cisplatin is reported
      to suppress glucose uptake, we investigated the correlation between glucose
      uptake and sensitivity to the drug. A fluorescent derivative of D-glucose, 2-NBDG
      (2-[N-(7-nitrobenz-2-oxa-1,3-diaxol-4-yl) amino]-2-deoxyglucose), was used to
      evaluate glucose uptake. Two ovarian cancer cell lines, SKOV-3 as a relatively
      resistant line and OVCAR-3 as a relatively sensitive line, were analyzed. Both
      cell lines had a decreased number of cells accompanied by cell death 24 h after
      cisplatin treatment, but not at 3 h. In contrast, glucose uptake was decreased 3
      h after high-dose cisplatin treatment, which correlated with the sensitivity to
      the drug at 24 h. The protein levels of glucose transporter 1 (GLUT1) did not
      change with cisplatin treatment. In contrast, the membrane localization of GLUT1
      disappeared after cisplatin treatment. Other cisplatin-resistant cell lines did
      not show an early decrease in glucose uptake after cisplatin treatment. The early
      decrease in glucose uptake and later cell death also correlated in cultured
      cancer cells from ovarian cancer patients. Thus, the decrease in glucose uptake
      at an early time point after high dose cisplatin treatment reflected cisplatin
      chemosensitivity in ovarian cancer cells. Measuring glucose uptake might be
      useful as a rapid evaluation of cisplatin chemosensitivity in ovarian cancer
      patients.

PMID- 20678157
TI  - High density of 'spiky' excrescences covering the surface of an erythrocyte
      infected with Plasmodium malariae.

PMID- 20678158
TI  - Plasma levels of advanced glycation end products are associated with haemolysis
      related organ complications in sickle cell patients.
AB  - Oxidative stress plays an important role in the pathophysiology of sickle cell
      disease (SCD). Plasma levels of advanced glycation end products (AGEs) are
      increased under oxidative conditions and are associated with disease severity in
      diabetes and inflammatory diseases. We investigated whether AGEs are increased in
      sickle cell patients and whether they are associated with SCD-related
      complications. Plasma levels of the AGEs pentosidine, N(epsilon) 
      (carboxymethyl)lysine (CML) and N(epsilon) -(carboxyethyl)lysine (CEL) were
      measured using single-column high performance liquid chromatography with
      fluorescence detection (pentosidine) and ultra performance liquid chromatography
      tandem mass spectrometry (CML and CEL). Plasma levels of pentosidine and CML were
      increased in HbSS/HbSbeta0-thalassaemia (n=60) and HbSC/HbSbeta(+) -thalassaemia
      (n=42) patients during steady state as compared to healthy HbAA controls (n=30)
      without increments during painful crisis. CEL levels were comparable between all
      groups. Pentosidine and CML levels correlated significantly to haemolytic rate
      during the clinically asymptomatic state while pentosidine was significantly
      related to the number of haemolysis-related organ complications. The increased
      plasma AGE levels in sickle cell patients and their association with haemolysis
      and haemolysis-related complications suggest AGEs might be implicated in the
      pathophysiology of the haemolytic phenotype of SCD. Measurement of AGEs might be
      useful in predicting organ complications in SCD.

PMID- 20678159
TI  - Application of genomics for risk stratification of childhood acute lymphoblastic
      leukaemia: from bench to bedside?
AB  - The remarkable progress in the treatment of childhood acute lymphoblastic
      leukaemia (ALL) has been based on the adjustment of therapy to subgroups of
      leukaemia stratified by their prognostic implications. Here, the contribution of
      the last decade of advanced genomic research on the clinical management of
      childhood ALL is examined. The application of genomics for routine diagnosis of
      ALL is feasible but depends on commercial development of appropriate certified
      platforms. The discovery of several novel high-risk markers, such as deletions in
      IKZF1 might be integrated into clinical protocols in the near future. Several
      novel targets for therapy have been identified and have led to phase I/II
      therapeutic trials. This and any future progress depends on the maintenance of
      high quality bio-banks including biological material and clinical data of each
      patient enrolled on a prospective clinical protocol.

PMID- 20678160
TI  - Synergistic and persistent effect of T-cell immunotherapy with anti-CD19 or anti
      CD38 chimeric receptor in conjunction with rituximab on B-cell non-Hodgkin
      lymphoma.
AB  - Using artificial receptors, it is possible to redirect the specificity of immune
      cells to tumour-associated antigens, which is expected to provide a useful
      strategy for cancer immunotherapy. Given that B-cell non-Hodgkin lymphoma (B-NHL)
      cells invariably express CD19 and CD38, these antigens may be suitable molecular
      candidates for such immunotherapy. We transduced human peripheral T cells or a T
      cell line with either anti-CD19-chimeric receptor (CAR) or anti-CD38-CAR, which
      contained an anti-CD19 or anti-CD38 antibody-derived single-chain variable domain
      respectively. Retroviral transduction led to anti-CD19-CAR or anti-CD38-CAR
      expression in T cells with high efficiency (>60%). The T cell line, Hut78, when
      transduced with anti-CD19-CAR or anti-CD38-CAR, exerted strong cytotoxicity
      against the B-NHL cell lines, HT and RL, and lymphoma cells isolated from
      patients. Interestingly, use of both CARs had an additive cytotoxic effect on HT
      cells in vitro. In conjunction with rituximab, human peripheral T cells
      expressing either anti-CD19-CAR or anti-CD38-CAR enhanced cytotoxicity against HT
      luciferase cells in xenografted mice. Moreover, the synergistic tumour
      suppressing activity was persistent in vivo for over 2 months. These results
      provide a powerful rationale for clinical testing of the combination of rituximab
      with autologous T cells carrying either CAR on aggressive or relapsed B-NHLs.

PMID- 20678161
TI  - Comparison of pedometer and accelerometer measures of physical activity during
      preschool time on 3- to 5-year-old children.
AB  - AIMS: To compare pedometer steps with accelerometer counts and to analyse minutes
      of engagement in light, moderate and vigorous physical activity in 3- to 5-year
      old children during preschool time. METHODS: Physical activity was recorded
      during preschool time for five consecutive days in 55 three- to five-year-old
      children. The children wore a Yamax SW200 pedometer and an Actigraph GTIM
      Monitor. RESULTS: The average time spent at preschool was 7.22 h/day with an
      average step of 7313 (+/-3042). Steps during preschool time increased with
      increasing age. The overall correlation between mean step counts and mean
      accelerometer counts (r = 0.67, p < 0.001), as well as time in light to vigorous
      activity (r = 0.76, p < 0.001), were moderately high. Step counts and moderate to
      vigorous physical activity minutes were poorly correlated in 3 years old (r =
      0.19, p < 0.191) and moderately correlated (r = 0.50, p < 0.001) for children 4
      to 5 years old. CONCLUSION: Correlation between the preschool children's
      pedometer-determined step counts and total engagement in physical activity during
      preschool time was moderately high. Children's step counts at preschool were low,
      and the time spent in moderate and vigorous physical activity at preschool was
      very short.

PMID- 20678162
TI  - Paediatric Hashimoto encephalopathy, refractory epilepsy and immunoglobulin
      treatment - unusual case report and review of the literature.
AB  - BACKGROUND:  Hashimoto encephalopathy (HE) is a rare autoimmune disorder. It is
      defined as a 'corticosteroid-responsive encephalopathy associated with
      thyroiditis'. CLINICAL OBSERVATION:   We describe a boy who suffered from HE,
      responded only to intravenous immunoglobulin therapy. This is the first case
      report of immunoglobulin therapy in paediatric HE. CONCLUSION:  After review of
      the literature, we recommend that unexplained encephalopathy in children should
      lead to evaluation of thyroid autoantibody titres. Immunoglobulins should be
      considered.

PMID- 20678163
TI  - Preterm appropriate for gestational age infants: size at birth explains
      subsequent growth.
AB  - AIM:  The aim was to evaluate growth and breastfeeding up to 18 months corrected
      age (CA) among preterm appropriate for gestational age (AGA) infants whose
      mothers initiated breastfeeding during the infants' hospital stay. METHODS:  One
      hundred and twenty-seven preterm AGA infants with a median birth weight of 2320
      (769-3250) g and gestational age 34.29 (25.00-35.86) weeks were evaluated up to a
      CA of 18 months. A retrospective, descriptive and comparative design was used.
      Data were obtained by chart review of hospital medical records and a
      questionnaire completed by the mothers. RESULTS: The changes in standard
      deviation scores (SDS) during the infants' hospital stay were -0.9 for weight, 
      0.3 for length and -0.5 for head circumference (HC). Infants with higher SDS at
      birth showed more negative changes from birth to discharge. Median increments in
      SDS from discharge to a CA of 2 months were as high as, or higher than, the loss
      from birth to discharge. CONCLUSION:  Preterm AGA infants with higher SDS for
      weight, length and HC at birth are at higher risk of inadequate growth during
      their hospital stay.

PMID- 20678164
TI  - Pneumococcal meningitis still with us in the era of conjugate vaccines.

PMID- 20678166
TI  - Maternal and fetal response to fetal persistent infection with bovine viral
      diarrhea virus.
AB  - PROBLEM: Infection of naive pregnant cows with non-cytopathic (ncp) bovine viral
      diarrhea virus (BVDV) results in transplacental infection of the fetus. Infection
      of the pregnant cow with ncp BVDV late in gestation (after day 150) results in
      transient infection (TI), as both the dam and fetus can mount an immune response
      to the virus. In contrast, if the fetus is infected with ncp BVDV early in
      gestation (before day 150), the fetal immune system is undeveloped and unable to
      recognize the virus as foreign. This results in induction of immune tolerance to
      the infecting BVDV strain and persistent infection (PI). METHODS: Infection of
      naive pregnant heifers with ncp BVDV2 on day 75 was hypothesized to induce
      differential gene expression in white blood cells of the dams and their fetuses,
      adversely affecting development and antiviral immune responses in PI fetuses.
      RESULTS: Gene expression differed in maternal blood cells in the presence of PI
      versus uninfected fetuses. PI adversely affected fetal development and antiviral
      responses, despite protective immune responses in the dam. CONCLUSION: Fetal PI
      with BVDV alters maternal immune function, compromises fetal growth and immune
      responses, and results in expression of maternal blood biomarkers that can be
      used to identify cows carrying PI fetuses.

PMID- 20678167
TI  - Role of endothelin and inflammatory cytokines in pre-eclampsia - A pilot North
      Indian study.
AB  - PROBLEM: Pre-eclampsia is new onset hypertension during pregnancy with
      proteinuria. The initiating event in pre-eclampsia is postulated to involve
      reduced placental perfusion, which leads to widespread dysfunction of the
      maternal vascular endothelium. Cytokines also appear to contribute to the
      development of the pathological condition. The aim of this study was to evaluate
      the role of cytokines in pre-eclampsia and to study the relationship between
      endothelin-1 and cytokines with the severity of the disease. METHOD OF STUDY:
      This cross-sectional study included 300 women with pre-eclampsia and 200 healthy
      pregnant women. Their blood samples were analyzed for endothelin-1 and
      inflammatory cytokines. RESULTS: Increased endothelin-1 and cytokines [tumor
      necrosis factor-alpha, interleukin-2 (IL-2) and gamma-interferon (IFN-gamma)]
      levels were found in pre-eclampsia (P < 0.001). Significant positive correlation
      was seen between endothelin-1 and cytokine level (IL-2 and IFNgamma) in the pre
      eclamptic group (P = 0.001). CONCLUSION: We conclude that pre-eclampsia is
      associated with increased levels of both endothelin-1 and circulating
      inflammatory cytokines, which points toward the role of endothelial and
      inflammatory components.

PMID- 20678168
TI  - Innate immunity and inflammatory response to Trichomonas vaginalis and bacterial
      vaginosis: relationship to HIV acquisition.
AB  - Most women contract HIV-1 through sexual intercourse with an infected partner.
      Highly prevalent, unreported and often asymptomatic lower genital tract
      infections, including bacterial vaginosis (BV) and trichomoniasis (Trichomonas
      vaginalis- TV), increase a woman's susceptibility to HIV-1 genital infection,
      given an exposure. A review of the literature from 1989 to the present was
      conducted. This article will review potential mechanisms by which BV and TV serve
      as HIV-1-enhancing cofactors including (i) initiation of a clinical or
      subclinical mucosal inflammatory response, (ii) alteration of innate mucosal
      immunity, (iii) alteration of normal vaginal microflora and pH, and (iv)
      weakening or breach of intact cervico-vaginal mucosa. The transmission of HIV-1,
      in the absence of cofactors, is poorly efficient. Understanding the mechanisms by
      which these infections enhance HIV-1 acquisition is important to designing
      effective, safe and evidence-based prevention modalities.

PMID- 20678169
TI  - Evolution and function of the uterine serpins (SERPINA14).
AB  - Uterine serpins (recently designated as SERPINA14) are hormonally induced
      proteins secreted in large quantities by the endometrial epithelium during
      pregnancy. The SERPINA14 proteins belong to the serine proteinase inhibitor
      (serpin) superfamily, but their apparent lack of inhibitory activity toward
      serine proteinases suggests that these proteins evolved a different function from
      the anti-proteinase activity typically found in most members of the serpin
      superfamily. The gene is present in a limited group of mammals in the
      Laurasiatheria superorder (ruminants, horses, pigs, dolphins and some carnivores)
      while being absent in primates, rodents, lagomorphs and marsupials. Thus, the
      gene is likely to have evolved by gene duplication after divergence of
      Laurasiatheria and to play an important role in pregnancy. That role may vary
      between species. In sheep, SERPINA14 probably serves an immunoregulatory role to
      prevent rejection of the fetal allograft. It is inhibitory to lymphocyte
      proliferation and natural killer cell function. In the pig, SERPINA14 is involved
      in iron transport to the fetus by binding to and stabilizing the iron-binding
      protein uteroferrin. It is possible that SERPINA14 has undergone divergence in
      function since the original emergence of the gene in a common ancestor of species
      possessing SERPINA14.

PMID- 20678170
TI  - Medawar redux - an overview on the use of farm animal models to elucidate
      principles of reproductive immunology.
AB  - Farm animals have been important models for the development of reproductive
      immunology. Two of the major concepts underpinning reproductive immunology, the
      idea of the fetal allograft and progesterone's role in regulation of uterine
      immunity, were developed using the bovine as a model. This volume of the American
      Journal of Reproductive Immunology is composed of review articles that highlight
      the continued relevance of farm animals as models for research in mammalian
      biology. It is important that a diverse array of genotypes are used to elucidate
      biological principles relevant to mammalian biology and human health because the
      nature of mammalian evolution has resulted in a situation where the genome of the
      most commonly used animal model, the laboratory mouse, is less similar to the
      human than other species like the cow. Moreover, the evolution of placental
      function has been accompanied by formation of new genes during recent evolution
      so that orthologs do not exist in any but closely related species. Given the
      infrastructure needs to study farm animal species, optimal utilization of these
      animals as models for biomedical research will require significant increases in
      funding to reverse a historical erosion of resources devoted to animal
      agricultural research.

PMID- 20678171
TI  - Come in and take your coat off - how host cells provide endocytosis for virus
      entry.
AB  - Viruses are intracellular parasites that rely upon the host cell machinery for
      their life cycle. Newly generated virus particles have to transmit their genomic
      information to uninfected cells/organisms. Viral entry is the process to gain
      access to viral replication sites within uninfected cells, a multistep course of
      events that starts with binding to target cells. Since viruses are simple in
      structure and composition and lack any locomotive capacity, viruses depend on
      hundreds of host cell proteins during entry. Most animal viruses take advantage
      of endocytosis to enter cells. Cell biological, morphological and biochemical
      studies, live cell imaging and systematic approaches have identified various new
      endocytic mechanisms besides clathrin-mediated endocytosis, macropinocytosis and
      caveolar/lipid raft-mediated endocytosis. Hence, studying virus entry has become
      ever more complex. This review provides a cell biological overview of the
      existing endocytic mechanisms and strategies used or potentially used by viruses
      to enter cells.

PMID- 20678173
TI  - Role of the NF-kappaB transcription pathway in the haemozoin- and 15-HETE
      mediated activation of matrix metalloproteinase-9 in human adherent monocytes.
AB  - Haemozoin (HZ, malarial pigment) is a crystalline ferriprotoporphyrin IX polymer
      derived from undigested host haemoglobin haem, present in late stages of
      Plasmodium falciparum-parasitized RBCs and in residual bodies shed after
      schizogony. It was shown previously that phagocytosed HZ or HZ-containing
      trophozoites increased monocyte matrix metalloproteinase-9 (MMP-9) activity and
      enhanced production of MMP-9-related cytokines TNF and IL-1beta. Here we show
      that in human monocytes the HZ/trophozoite phagocytosis effects and their
      recapitulation by 15(S,R)-hydroxy-6,8,11,13-eicosatetraenoic acid (15-HETE), a
      potent lipoperoxidation derivative generated by HZ from arachidonic acid via haem
      catalysis, were mediated via activation of NF-kappaB transcription pathway. After
      phagocytosis of HZ/trophozoites or treatment with 15-HETE, the NF-kappaB complex
      migrated to the nuclear fraction while the inhibitory cytosolic IkappaBalpha
      protein was phosphorylated and degraded. All HZ/trophozoite/15-HETE effects on
      MMP-9 activity and TNF/IL-1beta production were abrogated by quercetin,
      artemisinin and parthenolide, inhibitors of IkappaBalpha phosphorylation and
      subsequent degradation, NF-kappaB nuclear translocation, and NF-kappaB-p65
      binding to DNA respectively. In conclusion, enhanced activation of MMP-9, and
      release of pro-inflammatory cytokines TNF and IL-1beta, a triad of effects
      involved in malaria pathogenesis, elicited in human monocytes by trophozoite and
      HZ phagocytosis and recapitulated by 15-HETE, appear to be causally connected to
      persisting activation of the NF-kappaB system.

PMID- 20678172
TI  - Toxoplasma gondii protease TgSUB1 is required for cell surface processing of
      micronemal adhesive complexes and efficient adhesion of tachyzoites.
AB  - Host cell invasion by Toxoplasma gondii is critically dependent upon adhesive
      proteins secreted from the micronemes. Proteolytic trimming of microneme contents
      occurs rapidly after their secretion onto the parasite surface and is proposed to
      regulate adhesive complex activation to enhance binding to host cell receptors.
      However, the proteases responsible and their exact function are still unknown. In
      this report, we show that T. gondii tachyzoites lacking the microneme subtilisin
      protease TgSUB1 have a profound defect in surface processing of secreted
      microneme proteins. Notably parasites lack protease activity responsible for
      proteolytic trimming of MIC2, MIC4 and M2AP after release onto the parasite
      surface. Although complementation with full-length TgSUB1 restores processing,
      complementation of Deltasub1 parasites with TgSUB1 lacking the GPI anchor
      (Deltasub1::DeltaGPISUB1) only partially restores microneme protein processing.
      Loss of TgSUB1 decreases cell attachment and in vitro gliding efficiency leading
      to lower initial rates of invasion. Deltasub1 and Deltasub1::DeltaGPISUB1
      parasites are also less virulent in mice. Thus TgSUB1 is involved in micronemal
      protein processing and regulation of adhesive properties of macromolecular
      adhesive complexes involved in host cell invasion.

PMID- 20678174
TI  - Invasive fungal infections in paediatric patients.

PMID- 20678175
TI  - Diagnosis of invasive fungal infections in immunocompromised children.
AB  - Early recognition and rapid initiation of effective treatment is a prerequisite
      for successful management of children with invasive fungal infections. The
      increasing diversity of fungal pathogens in high-risk patients, the differences
      in the antifungal spectra of available agents and the increasing rates of
      resistance call for identification of the infecting isolate at the species level
      and for information on drug resistance, in order to provide state-of-the-art
      patient care. Microscopy and culture of appropriate specimens remain the
      reference standard for mycological diagnosis, despite difficulties in obtaining
      appropriate and/or sufficient specimens, long durations of culture and false
      negative results. Modern imaging studies and detection of circulating fungal cell
      wall components and DNA in blood and other body fluids or in affected tissues may
      improve the laboratory diagnosis of invasive mycoses.

PMID- 20678176
TI  - Human immunodeficiency virus type 1 fitness and tropism: concept, quantification,
      and clinical relevance.
AB  - Two distinct aspects of human immunodeficiency virus type 1 (HIV-1) biopathology
      with important implications for the management of treated patients have emerged
      during the last decade: changes in relative viral fitness, and viral tropism.
      First, it has been observed that HIV-1 accumulates deleterious mutations leading
      to drug resistance and different degrees of reduction in relative fitness during
      antiretroviral therapy (ART). Although the latter normally parallel a failure of
      ART resulting from selection of resistant mutants, the drop in viral replication
      capacity may be beneficial for the host. Moreover, specific antiviral compounds
      aimed at reducing viral fitness could be developed. Analysis of the determinants
      of viral fitness in highly evolving viral populations has shown that viral
      extinction may also be obtained by forcing highly dynamic viral populations
      through increased (lethal) mutagenesis that abolishes viral replication
      (violation of the error threshold). It could be of great interest in the near
      future to address this point with strategies specifically planned at the
      molecular level. Furthermore, diagnostic evaluation limited to the master
      sequence has low predictive value in rapidly evolving viral populations. These
      observations, together with the evidence that all of the methodologies currently
      used for fitness analysis have important limitations, strongly suggest that
      further research is warranted. This should use highly sensitive and flexible
      technologies to evaluate viral fitness directly in vivo or ex vivo, not only for
      the dominant mutants, but also for minority variants. Second, discovery of the
      two main co-receptors for HIV-1, CCR5 and CXCR4, has led to a better
      understanding of the interaction of the viral envelope with host cells and to the
      development of novel therapeutic agents that inhibit viral entry. In this
      perspective, analysis of HIV-1 tropism has acquired a major diagnostic role.

PMID- 20678177
TI  - Update on antifungal agents for paediatric patients.
AB  - Paediatric age groups display important differences in host biology, predisposing
      conditions, epidemiology and presentation of fungal infections relative to the
      adult population. During the past decade, several new antifungal agents have been
      developed. Although not all of these agents are yet approved for children, the
      paediatric development of antifungal agents has moved forwards in an exemplary
      manner. Invasive fungal infections will remain important causes of morbidity and
      mortality in immunocompromised paediatric patients. Whereas the availability of
      new therapeutic options is an important advance, antifungal therapy has become
      increasingly complex, and a thorough understanding of the available antifungal
      armamentarium is essential for the successful management of the individual
      patient. This article provides an update on the pharmacokinetics, safety and
      dosing of antifungal agents in paediatric patients, and their clinical
      indications.

PMID- 20678178
TI  - Early prosthetic joint infection: outcomes with debridement and implant retention
      followed by antibiotic therapy.
AB  - Recent expert reviews recommend a conservative surgical strategy - debridement
      and irrigation, antibiotics and implant retention (DAIR) - for most early post
      surgical prosthetic joint infections (PJI). However, differences exist in
      published series regarding success rates with DAIR, and the size of most series
      is small. In this prospective multicenter cohort study of early PJI managed by
      DAIR, factors associated with failure of the DAIR were analyzed. Out of 139 early
      PJI, 117 cases managed with DAIR were studied For 67 patients (57.3%), infection
      was cured and the implant was salvaged with definite antimicrobial therapy. In 35
      (29.9%) DAIR failed and removal of the prosthesis was necessary during follow-up.
      Finally, 15 patients (12.8%) needed chronic suppressive antimicrobial therapy due
      to suspected or confirmed persistent infection. Infections due to methicillin
      resistant S. aureus (72.7% failed; p 0.05) and those treated at one of the
      hospitals (80.0% failed; p <0.05) had worse outcomes, but only this last variable
      was associated with treatment failure following multivariate analysis. Seventy
      four per cent of patients who were successfully treated by DAIR and only 32.7% of
      the failures were able to walk without help or with one stick at the last follow
      up visit (p <0.05). In conclusion, a substantial proportion of patients with an
      early PJI may be successfully treated with DAIR and definite antimicrobial
      therapy. In more than half of these, the infection can be cured. Since
      identification of factors associated with failure of DAIR is not simple, we
      recommend offering DAIR to most patients with early PJI.

PMID- 20678179
TI  - The CAESAR project for in silico models for the REACH legislation.

PMID- 20678180
TI  - Assessment and validation of the CAESAR predictive model for bioconcentration
      factor (BCF) in fish.
AB  - BACKGROUND: Bioconcentration factor (BCF) describes the behaviour of a chemical
      in terms of its likelihood of concentrating in organisms in the environment. It
      is a fundamental property in recent regulations, such as the European Community
      Regulation on chemicals and their safe use or the Globally Harmonized System for
      classification, labelling and packaging. These new regulations consider the
      possibility of reducing or waiving animal tests using alternative methods, such
      as in silico methods. This study assessed and validated the CAESAR predictive
      model for BCF in fish. RESULTS: To validate the model, new experimental data were
      collected and used to create an external set, as a second validation set (a first
      validation exercise had been done just after model development). The performance
      of the model was compared with BCFBAF v3.00. For continuous values and for
      classification purposes the CAESAR BCF model gave better results than BCFBAF
      v3.00 for the chemicals in the applicability domain of the model. R2 and Q2 were
      good and accuracy in classification higher than 90%. Applying an offset of 0.5 to
      the compounds predicted with BCF close to the thresholds, the number of false
      negatives (the most dangerous errors) dropped considerably (less than 0.6% of
      chemicals). CONCLUSIONS: The CAESAR model for BCF is useful for regulatory
      purposes because it is robust, reliable and predictive. It is also fully
      transparent and documented and has a well-defined applicability domain, as
      required by REACH. The model is freely available on the CAESAR web site and easy
      to use. The reliability of the model reporting the six most similar compounds
      found in the CAESAR dataset, and their experimental and predicted values, can be
      evaluated.

PMID- 20678181
TI  - An open source multistep model to predict mutagenicity from statistical analysis
      and relevant structural alerts.
AB  - BACKGROUND: Mutagenicity is the capability of a substance to cause genetic
      mutations. This property is of high public concern because it has a close
      relationship with carcinogenicity and potentially with reproductive toxicity.
      Experimentally, mutagenicity can be assessed by the Ames test on Salmonella with
      an estimated experimental reproducibility of 85%; this intrinsic limitation of
      the in vitro test, along with the need for faster and cheaper alternatives, opens
      the road to other types of assessment methods, such as in silico structure
      activity prediction models.A widely used method checks for the presence of known
      structural alerts for mutagenicity. However the presence of such alerts alone is
      not a definitive method to prove the mutagenicity of a compound towards
      Salmonella, since other parts of the molecule can influence and potentially
      change the classification. Hence statistically based methods will be proposed,
      with the final objective to obtain a cascade of modeling steps with custom-made
      properties, such as the reduction of false negatives. RESULTS: A cascade model
      has been developed and validated on a large public set of molecular structures
      and their associated Salmonella mutagenicity outcome. The first step consists in
      the derivation of a statistical model and mutagenicity prediction, followed by
      further checks for specific structural alerts in the "safe" subset of the
      prediction outcome space. In terms of accuracy (i.e., overall correct predictions
      of both negative and positives), the obtained model approached the 85%
      reproducibility of the experimental mutagenicity Ames test. CONCLUSIONS: The
      model and the documentation for regulatory purposes are freely available on the
      CAESAR website. The input is simply a file of molecular structures and the output
      is the classification result.

PMID- 20678182
TI  - New public QSAR model for carcinogenicity.
AB  - BACKGROUND: One of the main goals of the new chemical regulation REACH
      (Registration, Evaluation and Authorization of Chemicals) is to fulfill the gaps
      in data concerned with properties of chemicals affecting the human health. (Q)SAR
      models are accepted as a suitable source of information. The EU funded CAESAR
      project aimed to develop models for prediction of 5 endpoints for regulatory
      purposes. Carcinogenicity is one of the endpoints under consideration. RESULTS:
      Models for prediction of carcinogenic potency according to specific requirements
      of Chemical regulation were developed. The dataset of 805 non-congeneric
      chemicals extracted from Carcinogenic Potency Database (CPDBAS) was used. Counter
      Propagation Artificial Neural Network (CP ANN) algorithm was implemented. In the
      article two alternative models for prediction carcinogenicity are described. The
      first model employed eight MDL descriptors (model A) and the second one twelve
      Dragon descriptors (model B). CAESAR's models have been assessed according to the
      OECD principles for the validation of QSAR. For the model validity we used a wide
      series of statistical checks. Models A and B yielded accuracy of training set
      (644 compounds) equal to 91% and 89% correspondingly; the accuracy of the test
      set (161 compounds) was 73% and 69%, while the specificity was 69% and 61%,
      respectively. Sensitivity in both cases was equal to 75%. The accuracy of the
      leave 20% out cross validation for the training set of models A and B was equal
      to 66% and 62% respectively. To verify if the models perform correctly on new
      compounds the external validation was carried out. The external test set was
      composed of 738 compounds. We obtained accuracy of external validation equal to
      61.4% and 60.0%, sensitivity 64.0% and 61.8% and specificity equal to 58.9% and
      58.4% respectively for models A and B. CONCLUSION: Carcinogenicity is a
      particularly important endpoint and it is expected that QSAR models will not
      replace the human experts opinions and conventional methods. However, we believe
      that combination of several methods will provide useful support to the overall
      evaluation of carcinogenicity. In present paper models for classification of
      carcinogenic compounds using MDL and Dragon descriptors were developed. Models
      could be used to set priorities among chemicals for further testing. The models
      at the CAESAR site were implemented in java and are publicly accessible.

PMID- 20678183
TI  - CAESAR models for developmental toxicity.
AB  - BACKGROUND: The new REACH legislation requires assessment of a large number of
      chemicals in the European market for several endpoints. Developmental toxicity is
      one of the most difficult endpoints to assess, on account of the complexity,
      length and costs of experiments. Following the encouragement of QSAR (in silico)
      methods provided in the REACH itself, the CAESAR project has developed several
      models. RESULTS: Two QSAR models for developmental toxicity have been developed,
      using different statistical/mathematical methods. Both models performed well. The
      first makes a classification based on a random forest algorithm, while the second
      is based on an adaptive fuzzy partition algorithm. The first model has been
      implemented and inserted into the CAESAR on-line application, which is java-based
      software that allows everyone to freely use the models. CONCLUSIONS: The CAESAR
      QSAR models have been developed with the aim to minimize false negatives in order
      to make them more usable for REACH. The CAESAR on-line application ensures that
      both industry and regulators can easily access and use the developmental toxicity
      model (as well as the models for the other four endpoints).

PMID- 20678184
TI  - Global QSAR models of skin sensitisers for regulatory purposes.
AB  - BACKGROUND: The new European Regulation on chemical safety, REACH, (Registration,
      Evaluation, Authorisation and Restriction of CHemical substances), is in the
      process of being implemented. Many chemicals used in industry require additional
      testing to comply with the REACH regulations. At the same time EU member states
      are attempting to reduce the number of animals used in experiments under the 3 Rs
      policy, (refining, reducing, and replacing the use of animals in laboratory
      procedures). Computational techniques such as QSAR have the potential to offer an
      alternative for generating REACH data. The FP6 project CAESAR was aimed at
      developing QSAR models for 5 key toxicological endpoints of which skin
      sensitisation was one. RESULTS: This paper reports the development of two global
      QSAR models using two different computational approaches, which contribute to the
      hybrid model freely available online. CONCLUSIONS: The QSAR models for assessing
      skin sensitisation have been developed and tested under stringent quality
      criteria to fulfil the principles laid down by the OECD. The final models,
      accessible from CAESAR website, offer a robust and reliable method of assessing
      skin sensitisation for regulatory use.

PMID- 20678185
TI  - Whole proteomes as internal standards in quantitative proteomics.
AB  - As mass-spectrometry-based quantitative proteomics approaches become increasingly
      powerful, researchers are taking advantage of well established methodologies and
      improving instrumentation to pioneer new protein expression profiling methods.
      For example, pooling several proteomes labeled using the stable isotope labeling
      by amino acids in cell culture (SILAC) method yields a whole-proteome stable
      isotope-labeled internal standard that can be mixed with a tissue-derived
      proteome for quantification. By increasing quantitative accuracy in the analysis
      of tissue proteomes, such methods should improve integration of protein
      expression profiling data with transcriptomic data and enhance downstream
      bioinformatic analyses. An accurate and scalable quantitative method to analyze
      tumor proteomes at the depth of several thousand proteins provides a powerful
      tool for global protein quantification of tissue samples and promises to redefine
      our understanding of tumor biology.

PMID- 20678186
TI  - Foetal testosterone and autistic traits in 18 to 24-month-old children.
AB  - BACKGROUND: Autism spectrum conditions have been characterised as an extreme
      presentation of certain male-typical psychological traits. In addition, several
      studies have established a link between prenatal exposure to testosterone and
      cognitive sex differences in later life, and one study found that foetal
      testosterone (FT) is positively correlated to autistic traits in 6 to 10 year-old
      children. In this study, we tested whether FT is positively correlated with
      autistic traits in toddlers aged 18-24 months. METHODS: Levels of FT were
      analysed in amniotic fluid and compared with autistic traits, measured using the
      Quantitative Checklist for Autism in Toddlers (Q-CHAT) in 129 typically
      developing toddlers aged between 18 and 24 months (mean +/- SD 19.25 +/- 1.52
      months). RESULTS: Sex differences were observed in Q-CHAT scores, with boys
      scoring significantly higher (indicating more autistic traits) than girls. In
      addition, we confirmed a significant positive relationship between FT levels and
      autistic traits. CONCLUSIONS: The current findings in children between 18 and 24
      months of age are consistent with observations in older children showing a
      positive association between elevated FT levels and autistic traits. Given that
      sex steroid-related gene variations are associated with autistic traits in
      adults, this new finding suggests that the brain basis of autistic traits may
      reflect individual differences in prenatal androgens and androgen-related genes.
      The consistency of findings in early childhood, later childhood and adulthood
      suggests that this is a robust association.

PMID- 20678187
TI  - A new family of phosphoinositide phosphatases in microorganisms: identification
      and biochemical analysis.
AB  - BACKGROUND: Phosphoinositide metabolism is essential to membrane dynamics and
      impinges on many cellular processes, including phagocytosis. Modulation of
      phosphoinositide metabolism is important for pathogenicity and virulence of many
      human pathogens, allowing them to survive and replicate in the host cells.
      Phosphoinositide phosphatases from bacterial pathogens are therefore key players
      in this modulation and constitute attractive targets for chemotherapy. MptpB, a
      virulence factor from Mycobacterium tuberculosis, has phosphoinositide
      phosphatase activity and a distinct active site P-loop signature HCXXGKDR that
      shares characteristics with eukaryotic lipid phosphatases and protein tyrosine
      phosphatases. We used this P-loop signature as a "diagnostic motif" to identify
      related putative phosphatases with phosphoinositide activity in other organisms.
      RESULTS: We found more than 200 uncharacterised putative phosphatase sequences
      with the conserved signature in bacteria, with some related examples in fungi and
      protozoa. Many of the sequences identified belong to recognised human pathogens.
      Interestingly, no homologues were found in any other organisms including Archaea,
      plants, or animals. Phylogenetic analysis revealed that these proteins are
      unrelated to classic eukaryotic lipid phosphatases. However, biochemical
      characterisation of those from Listeria monocytogenes and Leishmania major,
      demonstrated that, like MptpB, they have phosphatase activity towards
      phosphoinositides. Mutagenesis studies established that the conserved Asp and Lys
      in the P-loop signature (HCXXGKDR) are important in catalysis and substrate
      binding respectively. Furthermore, we provide experimental evidence that the
      number of basic residues in the P-loop is critical in determining activity
      towards poly-phosphoinositides. CONCLUSION: This new family of enzymes in
      microorganisms shows distinct sequence and biochemical characteristics to classic
      eukaryotic lipid phosphatases and they have no homologues in humans. This study
      provides a foundation for examining the biological role of this new family of
      phosphatases and their potential as pharmaceutical targets against infectious
      diseases.

PMID- 20678188
TI  - Predictive value of CpG island methylator phenotype for tumor recurrence in
      hepatitis B virus-associated hepatocellular carcinoma following liver
      transplantation.
AB  - BACKGROUND: CpG island methylator phenotype (CIMP), in which multiple genes
      concordantly methylated, has been demonstrated to be associated with progression,
      recurrence, as well as overall survival in some types of cancer. METHODS: We
      examined the promoter methylation status of seven genes including P16, CDH1,
      GSTP1, DAPK, XAF1, SOCS1 and SYK in 65 cases of HCC treated with LT by
      methylation-specific PCR. CIMP+ was defined as having three or more genes that
      are concordantly methylated. The relationship between CIMP status and
      clinicopathological parameters, as well as tumor recurrence was further analyzed.
      RESULTS: CIMP+ was more frequent in HCC with AFP > 400 ng/ml than those with AFP
      <or= 400 ng/ml (P = 0.017). In addition, patients with CIMP+ were prone to have
      multiple tumor numbers than those with CIMP- (P = 0.007). Patients with CIMP+
      tumors had significantly worse recurrence-free survival (RFS) than patients with
      CIMP-tumors by Kaplan-Meier estimates (P = 0.004). Multivariate analysis also
      revealed that CIMP status might be a novel independent prognostic factor of RFS
      for HCC patients treated with LT (HR: 3.581; 95% CI: 1.473-8.710, P = 0.005).
      CONCLUSION: Our results suggested that CIMP could serve as a new prognostic
      biomarker to predict the risk of tumor recurrence in HCC after transplantation.

PMID- 20678189
TI  - Should the provision of home help services be contained?: validation of the new
      preventive care policy in Japan.
AB  - BACKGROUND: To maintain the sustainability of public long-term care insurance
      (LTCI) in Japan, a preventive care policy was introduced in 2006 that seeks to
      promote active improvement in functional status of elderly people who need only
      light care. This policy promotes the use of day care services to facilitate
      functional improvement, and contains the use of home help services that provide
      instrumental activity of daily living (IADL) support. However, the validity of
      this approach remains to be demonstrated. METHODS: Subjects comprised 241 people
      aged 65 years and over who had recently been certified as being eligible for the
      lightest eligibility level and had began using either home help or day care
      services between April 2007 and October 2008 in a suburban city of Tokyo. A
      retrospective cohort study was conducted ending October 2009 to assess changes in
      the LTCI eligibility level of these subjects. Cox's proportional hazards model
      was used to calculate the relative risk of declining in function to eligibility
      Level 4 among users of the respective services. RESULTS: Multivariate analysis
      adjusted for factors related to service use demonstrated that the risk of decline
      in functional status was lower for users of home help services than for users of
      day care services (HR = 0.55, 95% CI: 0.31-0.98). The same result was obtained
      when stratified by whether the subject lived with family or not. Furthermore,
      those who used two or more hours of home help services did not show an increase
      in risk of decline when compared with those who used less than two hours.
      CONCLUSIONS: No evidence was obtained to support the effectiveness of the policy
      of promoting day care services and containing home help services for those
      requiring light care.

PMID- 20678190
TI  - Antenatal HIV-1 RNA load and timing of mother to child transmission; a nested
      case-control study in a resource poor setting.
AB  - OBJECTIVE: To determine HIV-1 RNA load during the third trimester of pregnancy
      and evaluate its effect on in utero and intra-partum/postpartum transmissions in
      a breastfeeding population. DESIGN: A nested case-control study within a PMTCT
      cohort of antiretroviral therapy naive pregnant women and their infants. METHODS:
      A case was a mother who transmitted HIV-1 to her infant (transmitter) who was
      matched to one HIV-1 positive but non-transmitting mother (control). RESULTS:
      From a cohort of 691 pregnant women, 177 (25.6%) were HIV-1 positive at
      enrollment and from these 29 (23%) transmitted HIV-1 to their infants, 10 and 19
      during in utero and intra-partum/postpartum respectively. Twenty-four mothers
      sero-converted after delivery and three transmitted HIV-1 to their infants. Each
      unit increase in log10 viral load was associated with a 178 cells/mm(3) and 0.2
      g/dL decrease in TLC and hemoglobin levels, p = 0.048 and 0.021 respectively, and
      a 29% increase in the risk of transmission, p = 0.023. Intra-partum/postpartum
      transmitters had significantly higher mean viral load relative to their matched
      controls, p = 0.034. CONCLUSION: Antenatal serum HIV-1 RNA load, TLC and
      hemoglobin levels were significantly associated with vertical transmission but
      this association was independent of transmission time. This finding supports the
      rationale for preventive strategies designed to reduce vertical transmission by
      lowering maternal viral load.

PMID- 20678191
TI  - Functional interaction between Env oncogene from Jaagsiekte sheep retrovirus and
      tumor suppressor Sprouty2.
AB  - BACKGROUND: Jaagsiekte sheep retrovirus (JSRV) is a type D retrovirus capable of
      transforming target cells in vitro and in vivo. The Envelope (Env) gene from JSRV
      and from related retroviruses can induce oncogenic transformation, although the
      detailed mechanism is yet to be clearly understood. Host cell factors are
      envisaged to play a critical determining role in the regulation of Env-mediated
      cell transformation. RESULTS: JSRV Env-mediated transformation of a lung
      adenocarcinoma cell line induced rapid proliferation, anchorage-independent
      growth and tumor formation, but completely abrogated the migration ability. An
      analysis of the signaling scenario in the transformed cells suggested the
      involvement of the ERK pathway regulated by Sprouty2 in cell migration, and the
      PI3K-Akt and STAT3 pathways in proliferation and anchorage-independence. On the
      other hand, in a normal lung epithelial cell line, Env-mediated transformation
      only decreased the migration potential while the other functions remained
      unaltered. We observed that Env induced the expression of a tumor suppressor,
      Sprouty2, suggesting a correlation between Env-effect and Sprouty2 expression.
      Overexpression of Sprouty2 per se not only decreased the migratory potential and
      tumor formation potential of the target cells but also made them resistant to
      subsequent Env-mediated transformation. On the other hand, over expression of the
      functional mutants of Sprouty2 had no inhibitory effect, confirming the role of
      Sprouty2 as a tumor suppressor. CONCLUSIONS: Our studies demonstrate that Env and
      Sprouty2 have a functional relationship, probably through shared signaling
      network. Sprouty2 functions as a tumor suppressor regulating oncogenic
      transformation of cells, and it therefore has the potential to be exploited as a
      therapeutic anti-cancer agent.

PMID- 20678192
TI  - Reassuring and managing patients with concerns about swine flu: qualitative
      interviews with callers to NHS Direct.
AB  - BACKGROUND: During the early stages of the 2009 swine flu (influenza H1N1)
      outbreak, the large majority of patients who contacted the health services about
      the illness did not have it. In the UK, the NHS Direct telephone service was used
      by many of these patients. We used qualitative interviews to identify the main
      reasons why people approached NHS Direct with concerns about swine flu and to
      identify aspects of their contact which were reassuring, using a framework
      approach. METHODS: 33 patients participated in semi-structured interviews. All
      patients had telephoned NHS Direct between 11 and 14 May with concerns about
      swine flu and had been assessed as being unlikely to have the illness. RESULTS:
      Reasons for seeking advice about swine flu included: the presence of unexpectedly
      severe flu-like symptoms; uncertainties about how one can catch swine flu;
      concern about giving it to others; pressure from friends or employers; and
      seeking 'peace of mind.' Most participants found speaking to NHS Direct
      reassuring or useful. Helpful aspects included: having swine flu ruled out;
      receiving an alternative explanation for symptoms; clarification on how swine flu
      is transmitted; and the perceived credibility of NHS Direct. No-one reported
      anything that had increased their anxiety and only one participant subsequently
      sought additional advice about swine flu from elsewhere. CONCLUSIONS: Future
      major incidents involving other forms of chemical, biological or radiological
      hazards may also cause large numbers of unexposed people to seek health advice.
      Our data suggest that providing telephone triage and information is helpful in
      such instances, particularly where advice can be given via a trusted, pre
      existing service.

PMID- 20678193
TI  - No evidence for XMRV association in pediatric idiopathic diseases in France.
AB  - Retroviruses have been linked to a variety of diseases such as neoplastic and
      immunodeficiency disorders and neurologic and respiratory diseases. Recently, a
      novel infectious human retrovirus, the xenotropic murine leukemia virus-related
      virus (XMRV), has been identified in cohorts of patients with either a familial
      type of prostate cancer or chronic fatigue syndrome. The apparent unrelatedness
      of these diseases raised the question of the potential involvement of XMRV in
      other diseases.Here, we investigated the presence of XMRV in a selection of
      pediatric idiopathic infectious diseases with symptoms that are suggestive of a
      retroviral infection, as well as in children with respiratory diseases and in
      adult patients with spondyloarthritis (SpA). Using a XMRV env-nested PCR, we
      screened 72 DNA samples obtained from 62 children hospitalized in the Montpellier
      university hospital (France) for hematological, neurological or inflammatory
      pathologies, 80 DNA samples from nasopharyngeal aspirates from children with
      respiratory diseases and 19 DNA samples from SpA. None of the samples tested was
      positive for XMRV or MLV-like env sequences, indicating that XMRV is not involved
      in these pathologies.

PMID- 20678194
TI  - Retrotransposon vectors for gene delivery in plants.
AB  - BACKGROUND: Retrotransposons are abundant components of plant genomes, and
      although some plant retrotransposons have been used as insertional mutagens,
      these mobile genetic elements have not been widely exploited for plant genome
      manipulation. In vertebrates and yeast, retrotransposons and retroviruses are
      routinely altered to carry additional genes that are copied into complementary
      (c)DNA through reverse transcription. Integration of cDNA results in gene
      delivery; recombination of cDNA with homologous chromosomal sequences can create
      targeted gene modifications. Plant retrotransposon-based vectors, therefore, may
      provide new opportunities for plant genome engineering. RESULTS: A
      retrotransposon vector system was developed for gene delivery in plants based on
      the Tnt1 element from Nicotiana tabacum. Mini-Tnt1 transfer vectors were
      constructed that lack coding sequences yet retain the 5' and 3' long terminal
      repeats (LTRs) and adjacent cis sequences required for reverse transcription. The
      internal coding region of Tnt1 was replaced with a neomycin phosphotransferase
      gene to monitor replication by reverse transcription. Two different mini-Tnt1 s
      were developed: one with the native 5' LTR and the other with a chimeric 5' LTR
      that had the first 233 bp replaced by the CaMV 35 S promoter. After transfer into
      tobacco protoplasts, both vectors undergo retrotransposition using GAG and POL
      proteins provided in trans by endogenous Tnt1 elements. The transposition
      frequencies of mini-Tnt1 vectors are comparable with native Tnt1 elements, and
      like the native elements, insertion sites are within or near coding sequences. In
      this paper, we provide evidence that template switching occurs during mini-Tnt1
      reverse transcription, indicating that multiple copies of Tnt1 mRNA are packaged
      into virus-like particles. CONCLUSIONS: Our data demonstrate that mini-Tnt1
      vectors can replicate efficiently in tobacco cells using GAG and POL proteins
      provided in trans by native Tnt1 elements. This suggests that helper Tnt1
      constructs can be developed to enable a Tnt1-based two-component vector system
      that could be used in other plant species. Such a vector system may prove useful
      for gene delivery or the production of cDNA that can serve as a donor molecule
      for gene modification through homologous recombination.

PMID- 20678195
TI  - Improving simultaneous saccharification and co-fermentation of pretreated wheat
      straw using both enzyme and substrate feeding.
AB  - BACKGROUND: Simultaneous saccharification and co-fermentation (SSCF) has been
      recognized as a feasible option for ethanol production from xylose-rich
      lignocellulosic materials. To reach high ethanol concentration in the broth, a
      high content of water-insoluble solids (WIS) is needed, which creates mixing
      problems and, furthermore, may decrease xylose uptake. Feeding of substrate has
      already been proven to give a higher xylose conversion than a batch SSCF. In the
      current work, enzyme feeding, in addition to substrate feeding, was investigated
      as a means of enabling a higher WIS content with a high xylose conversion in SSCF
      of a xylose-rich material. A recombinant xylose-fermenting strain of
      Saccharomyces cerevisiae (TMB3400) was used for this purpose in fed-batch SSCF
      experiments of steam-pretreated wheat straw. RESULTS: By using both enzyme and
      substrate feeding, the xylose conversion in SSCF could be increased from 40% to
      50% in comparison to substrate feeding only. In addition, by this design of the
      feeding strategy, it was possible to process a WIS content corresponding to 11%
      in SSCF and obtain an ethanol yield on fermentable sugars of 0.35 g g-1.
      CONCLUSION: A combination of enzyme and substrate feeding was shown to enhance
      xylose uptake by yeast and increase overall ethanol yield in SSCF. This is
      conceptually important for the design of novel SSCF processes aiming at high
      ethanol titers. Substrate feeding prevents viscosity from becoming too high and
      thereby allows a higher total amount of WIS to be added in the process. The
      enzyme feeding, furthermore, enables keeping the glucose concentration low, which
      kinetically favors xylose uptake and results in a higher xylose conversion.

PMID- 20678197
TI  - Evidence for a bimodal distribution of Escherichia coli doubling times below a
      threshold initial cell concentration.
AB  - BACKGROUND: In the process of developing a microplate-based growth assay, we
      discovered that our test organism, a native E. coli isolate, displayed very
      uniform doubling times (tau) only up to a certain threshold cell density. Below
      this cell concentration (<or= 100 -1,000 CFU mL-1 ; <or= 27-270 CFU well-1) we
      observed an obvious increase in the tau scatter. RESULTS: Working with a food
      borne E. coli isolate we found that tau values derived from two different
      microtiter platereader-based techniques (i.e., optical density with growth time
      {=OD[t]} fit to the sigmoidal Boltzmann equation or time to calculated 1/2
      maximal OD {=tm} as a function of initial cell density {=tm[CI]}) were in
      excellent agreement with the same parameter acquired from total aerobic plate
      counting. Thus, using either Luria-Bertani (LB) or defined (MM) media at 37
      degrees C, tau ranged between 17-18 (LB) or 51-54 (MM) min. Making use of such
      OD[t] data we collected many observations of tau as a function of manifold
      initial or starting cell concentrations (CI). We noticed that tau appeared to be
      distributed in two populations (bimodal) at low CI. When CI <or=100 CFU mL-1
      (stationary phase cells in LB), we found that about 48% of the observed tau
      values were normally distributed around a mean (mutau1) of 18 +/- 0.68 min (+/-
      sigmatau1) and 52% with mutau2 = 20 +/- 2.5 min (n = 479). However, at higher
      starting cell densities (CI>100 CFU mL-1), the tau values were distributed
      unimodally (mutau = 18 +/- 0.71 min; n = 174). Inclusion of a small amount of
      ethyl acetate to the LB caused a collapse of the bimodal to a unimodal form.
      Comparable bimodal tau distribution results were also observed using E. coli
      cells diluted from mid-log phase cultures. Similar results were also obtained
      when using either an E. coli O157:H7 or a Citrobacter strain. When sterile
      filtered LB supernatants, which formerly contained relatively low concentrations
      of bacteria(1,000-10,000 CFU mL-1), were employed as a diluent, there was an
      evident shift of the two populations towards each other but the bimodal effect
      was still apparent using either stationary or log phase cells. CONCLUSION: These
      data argue that there is a dependence of growth rate on starting cell density.

PMID- 20678196
TI  - Association of invasion-promoting tenascin-C additional domains with breast
      cancers in young women.
AB  - INTRODUCTION: Tenascin-C (TNC) is a large extracellular matrix glycoprotein that
      shows prominent stromal expression in many solid tumours. The profile of isoforms
      expressed differs between cancers and normal breast, with the two additional
      domains AD1 and AD2 considered to be tumour associated. The aim of the present
      study was to investigate expression of AD1 and AD2 in normal, benign and
      malignant breast tissue to determine their relationship with tumour
      characteristics and to perform in vitro functional assays to investigate the role
      of AD1 in tumour cell invasion and growth. METHODS: Expression of AD1 and AD2 was
      related to hypoxanthine phosphoribosyltransferase 1 as a housekeeping gene in
      breast tissue using quantitative RT-PCR, and the results were related to
      clinicopathological features of the tumours. Constructs overexpressing an AD1
      containing isoform (TNC-14/AD1/16) were transiently transfected into breast
      carcinoma cell lines (MCF-7, T-47 D, ZR-75-1, MDA-MB-231 and GI-101) to assess
      the effect in vitro on invasion and growth. Statistical analysis was performed
      using a nonparametric Mann-Whitney test for comparison of clinicopathological
      features with levels of TNC expression and using Jonckheere-Terpstra trend
      analysis for association of expression with tumour grade. RESULTS: Quantitative
      RT-PCR detected AD1 and AD2 mRNA expression in 34.9% and 23.1% of 134 invasive
      breast carcinomas, respectively. AD1 mRNA was localised by in situ hybridisation
      to tumour epithelial cells, and more predominantly to myoepithelium around
      associated normal breast ducts. Although not tumour specific, AD1 and AD2
      expression was significantly more frequent in carcinomas in younger women (age
      <=40 years; P < 0.001) and AD1 expression was also associated with oestrogen
      receptor-negative and grade 3 tumours (P < 0.05). AD1 was found to be
      incorporated into a tumour-specific isoform, not detected in normal tissues.
      Overexpression of the TNC-14/AD1/16 isoform significantly enhanced tumour cell
      invasion (P < 0.01) and growth (P < 0.01) over base levels. CONCLUSIONS: Together
      these data suggest a highly significant association between AD-containing TNC
      isoforms and breast cancers in younger women (age <=40 years), which may have
      important functional significance in vivo.

PMID- 20678198
TI  - Reliability and validity of the Spanish version of the Child Health and Illness
      Profile (CHIP) Child-Edition, Parent Report Form (CHIP-CE/PRF).
AB  - BACKGROUND: The objectives of the study were to assess the reliability, and the
      content, construct, and convergent validity of the Spanish version of the CHIP
      CE/PRF, to analyze parent-child agreement, and compare the results with those of
      the original U.S. version. METHODS: Parents from a representative sample of
      children aged 6-12 years were selected from 9 primary schools in Barcelona. Test
      retest reliability was assessed in a convenience subsample of parents from 2
      schools. Parents completed the Spanish version of the CHIP-CE/PRF. The Achenbach
      Child Behavioural Checklist (CBCL) was administered to a convenience subsample.
      RESULTS: The overall response rate was 67% (n = 871). There was no floor effect.
      A ceiling effect was found in 4 subdomains. Reliability was acceptable at the
      domain level (internal consistency = 0.68-0.86; test-retest intraclass
      correlation coefficients = 0.69-0.85). Younger girls had better scores on
      Satisfaction and Achievement than older girls. Comfort domain score was lower
      (worse) in children with a probable mental health problem, with high effect size
      (ES = 1.45). The level of parent-child agreement was low (0.22-0.37).
      CONCLUSIONS: The results of this study suggest that the parent version of the
      Spanish CHIP-CE has acceptable psychometric properties although further research
      is needed to check reliability at sub-domain level. The CHIP-CE parent report
      form provides a comprehensive, psychometrically sound measure of health for
      Spanish children 6 to 12 years old. It can be a complementary perspective to the
      self-reported measure or an alternative when the child is unable to complete the
      questionnaire. In general, the results are similar to the original U.S. version.

PMID- 20678199
TI  - Optimization of total protein and activity assays for the detection of MMP-12 in
      induced human sputum.
AB  - BACKGROUND: Proteolysis of matrix components, in particular elastin, is a major
      contributing factor to the development of lung diseases such as emphysema and
      chronic obstructive pulmonary disease (COPD). MMP-12 (macrophage elastase) is a
      protease known to be involved in the progression of lung disease. The relatively
      low abundance of MMP-12 has precluded the development of quantitative assays that
      can accurately measure MMP-12 protein levels and activity across cohorts of
      healthy and diseased individuals. METHODS: Commercial antibodies were screened
      for performance in sandwich ELISA and capture FRET activity assay formats.
      Precision, accuracy, sensitivity, dilution linearity, and spike recovery were
      evaluated using sputum samples. RESULTS: Total protein and capture FRET activity
      assays were developed that were sensitive enough to detect MMP-12 in 37 of 38
      donor sputum samples. A comparison of results between the two assays shows that a
      majority of sputum MMP-12 is in the active form. No differences were seen between
      normal, asthmatic, and COPD donors. CONCLUSION: Sensitive and quantitative assays
      for both MMP-12 activity and total protein in human induced sputum have been
      developed. These assays can be used to evaluate MMP-12 as a biomarker for lung
      disease, and to monitor efficacy of potential therapeutic compounds.

PMID- 20678200
TI  - Integrative analysis of large scale expression profiles reveals core
      transcriptional response and coordination between multiple cellular processes in
      a cyanobacterium.
AB  - BACKGROUND: Cyanobacteria are the only known prokaryotes capable of oxygenic
      photosynthesis. They play significant roles in global biogeochemical cycles and
      carbon sequestration, and have recently been recognized as potential vehicles for
      production of renewable biofuels. Synechocystis sp. PCC 6803 has been extensively
      used as a model organism for cyanobacterial studies. DNA microarray studies in
      Synechocystis have shown varying degrees of transcriptome reprogramming under
      altered environmental conditions. However, it is not clear from published work
      how transcriptome reprogramming affects pre-existing networks of fine-tuned
      cellular processes. RESULTS: We have integrated 163 transcriptome data sets
      generated in response to numerous environmental and genetic perturbations in
      Synechocystis. Our analyses show that a large number of genes, defined as the
      core transcriptional response (CTR), are commonly regulated under most
      perturbations. The CTR contains nearly 12% of Synechocystis genes found on its
      chromosome. The majority of genes in the CTR are involved in photosynthesis,
      translation, energy metabolism and stress protection. Our results indicate that a
      large number of differentially regulated genes identified in most reported
      studies in Synechocystis under different perturbations are associated with the
      general stress response. We also find that a majority of genes in the CTR are
      coregulated with 25 regulatory genes. Some of these regulatory genes have been
      implicated in cellular responses to oxidative stress, suggesting that reactive
      oxygen species are involved in the regulation of the CTR. A Bayesian network,
      based on the regulation of various KEGG pathways determined from the expression
      patterns of their associated genes, has revealed new insights into the
      coordination between different cellular processes. CONCLUSION: We provide here
      the first integrative analysis of transcriptome data sets generated in a
      cyanobacterium. This compilation of data sets is a valuable resource to
      researchers for all cyanobacterial gene expression related queries. Importantly,
      our analysis provides a global description of transcriptional reprogramming under
      different perturbations and a basic framework to understand the strategies of
      cellular adaptations in Synechocystis.

PMID- 20678201
TI  - Subchondral bone microstructural damage by increased remodelling aggravates
      experimental osteoarthritis preceded by osteoporosis.
AB  - INTRODUCTION: Osteoporosis (OP) increases cartilage damage in a combined rabbit
      model of OP and osteoarthritis (OA). Accordingly, we assessed whether
      microstructure impairment at subchondral bone aggravates cartilage damage in this
      experimental model. METHODS: OP was induced in 20 female rabbits, by ovariectomy
      and intramuscular injections of methylprednisolone hemisuccinate for four weeks.
      Ten healthy animals were used as controls. At week 7, OA was surgically induced
      in left knees of all rabbits. At 22 weeks, after sacrifice, microstructure
      parameters were assessed by micro-computed tomography, and osteoprotegerin (OPG),
      receptor activator of nuclear factor-kappaB ligand (RANKL), alkaline phosphatase
      (ALP) and metalloproteinase 9 (MMP9) protein expressions were evaluated by
      Western Blot at subchondral bone. In addition, cartilage damage was estimated
      using the histopathological Mankin score. Mann-Whitney and Spearman statistical
      tests were performed as appropriate, using SPSS software v 11.0. Significant
      difference was established at P < 0.05. RESULTS: Subchondral bone area/tissue
      area, trabecular thickness and polar moment of inertia were diminished in OPOA
      knees compared with control or OA knees (P < 0.05). A decrease of plate
      thickness, ALP expression and OPG/RANKL ratio as well as an increased fractal
      dimension and MMP9 expression occurred at subchondral bone of OA, OP and OPOA
      knees vs. controls (P < 0.05). In addition, the severity of cartilage damage was
      increased in OPOA knees vs. controls (P < 0.05). Remarkably, good correlations
      were observed between structural and remodelling parameters at subchondral bone,
      and furthermore, between subchondral structural parameters and cartilage Mankin
      score. CONCLUSIONS: Microstructure impairment at subchondral bone associated with
      an increased remodelling aggravated cartilage damage in OA rabbits with previous
      OP. Our results suggest that an increased subchondral bone resorption may account
      for the exacerbation of cartilage damage when early OA and OP coexist
      simultaneously in same individuals.

PMID- 20678202
TI  - Comparison of estrogens and estrogen metabolites in human breast tissue and
      urine.
AB  - BACKGROUND: An important aspect of the link between estrogen and breast cancer is
      whether urinary estrogen levels are representative of the intra-tissue levels of
      bioavailable estrogens. METHODS: This study compares 15 estrogen and estrogen
      metabolite levels in breast tissue and urine of 9 women with primary breast
      cancer using a quantitative liquid chromatography-mass spectrometry method.
      RESULTS: The average levels of estrogens (estrone, 17 beta-estradiol) were
      significantly higher in breast tissue than in urine. Both the 2 and the 16
      hydroxylation pathways were less represented in breast tissue than urine; no
      components of the 4-hydroxypathway were detected in breast tissue, while 4
      hydroxyestrone was measured in urine. However, the 2/16 ratio was similar in
      urine and breast tissue. Women carrying the variant CYP1B1 genotype (Leu/Val and
      Val/Val) showed significantly lower overall estrogen metabolite, estrogen, and 16
      hydroxylation pathway levels in breast tissue in comparison to women carrying the
      wild type genotype. No effect of the CYP1B1 polymorphism was observed in urinary
      metabolites. CONCLUSIONS: The urinary 2/16 ratio seems a good approximation of
      the ratio observed in breast tissue. Metabolic genes may have an important role
      in the estrogen metabolism locally in tissues where the gene is expressed, a role
      that is not readily observable when urinary measurements are performed.

PMID- 20678203
TI  - Variations in the quality and costs of end-of-life care, preferences and
      palliative outcomes for cancer patients by place of death: the QUALYCARE study.
AB  - BACKGROUND: Emerging trends and new policies suggest that more cancer patients
      might die at home in the future. However, not all have equal chances of achieving
      this. Furthermore, there is lack of evidence to support that those who die at
      home experience better care and a better death than those who die as inpatients.
      The QUALYCARE study aims to examine variations in the quality and costs of end-of
      life care, preferences and palliative outcomes associated with dying at home or
      in an institution for cancer patients. METHODS/DESIGN: Mortality followback
      survey (with a nested case-control study of home vs. hospital deaths) conducted
      with bereaved relatives of cancer patients in four Primary Care Trusts in London.
      Potential participants are identified from death registrations and approached by
      the Office for National Statistics in complete confidence. Data are collected via
      a postal questionnaire to identify the informal and formal care received in the
      three months before death and the associated costs, relatives' satisfaction with
      care, and palliative outcomes for the patients and their relatives. A well
      established questionnaire to measure relatives' views on the care integrates four
      brief and robust tools - the Client Service Receipt Inventory, the Palliative
      Outcome Scale, the EQ-5 D and the Texas Revised Inventory of Grief. Further
      questions assess patients and relatives' preferences for place of death. The
      survey aims to include 500 bereaved relatives (140 who experienced a home death,
      205 a hospital death, 115 a hospice death and 40 a nursing home death). Bivariate
      and multivariate analyses will explore differences in place of death and place of
      end-of-life care, in preferences for place of death, patients' palliative
      outcomes and relatives' bereavement outcomes, in relation to place of death.
      Factors influencing death at home and the costs of end-of-life care by place of
      death will be identified. DISCUSSION: Collecting data on end-of-life care
      retrospectively from bereaved relatives has ethical, practical and scientific
      challenges. QUALYCARE has been carefully designed to address these challenges in
      a robust and ethically sound population-based survey. By discovering variations
      in the underlying individual reality of place of death for people dying from
      cancer and their families, this study will advance our understanding of end-of
      life care and, we hope, improve care for cancer patients and their families in
      the future. TRIAL REGISTRATION: National Institute of Health Research (NIHR)
      Clinical Research Network Portfolio. UKCRN7041.

PMID- 20678204
TI  - Angiogenesis inhibitors in the treatment of prostate cancer.
AB  - Prostate cancer remains a significant public health problem, with limited
      therapeutic options in the setting of castrate-resistant metastatic disease.
      Angiogenesis inhibition is a relatively novel antineoplastic approach, which
      targets the reliance of tumor growth on the formation of new blood vessels. This
      strategy has been used successfully in other solid tumor types, with the FDA
      approval of anti-angiogenic agents in breast, lung, colon, brain, and kidney
      cancer. The application of anti-angiogenic therapy to prostate cancer is reviewed
      in this article, with attention to efficacy and toxicity results from several
      classes of anti-angiogenic agents. Ultimately, the fate of anti-angiogenic agents
      in prostate cancer rests on the eagerly anticipated results of several key phase
      III studies.

PMID- 20678205
TI  - Mental health policy process: a comparative study of Ghana, South Africa, Uganda
      and Zambia.
AB  - BACKGROUND: Mental illnesses are increasingly recognised as a leading cause of
      disability worldwide, yet many countries lack a mental health policy or have an
      outdated, inappropriate policy. This paper explores the development of
      appropriate mental health policies and their effective implementation. It reports
      comparative findings on the processes for developing and implementing mental
      health policies in Ghana, South Africa, Uganda and Zambia as part of the Mental
      Health and Poverty Project. METHODS: The study countries and respondents were
      purposively selected to represent different levels of mental health policy and
      system development to allow comparative analysis of the factors underlying the
      different forms of mental health policy development and implementation. Data were
      collected using semi-structured interviews and document analysis. Data analysis
      was guided by conceptual framework that was developed for this purpose. A
      framework approach to analysis was used, incorporating themes that emerged from
      the data and from the conceptual framework. RESULTS: Mental health policies in
      Ghana, South Africa, Uganda and Zambia are weak, in draft form or non-existent.
      Mental health remained low on the policy agenda due to stigma and a lack of
      information, as well as low prioritisation by donors, low political priority and
      grassroots demand. Progress with mental health policy development varied and
      respondents noted a lack of consultation and insufficient evidence to inform
      policy development. Furthermore, policies were poorly implemented, due to factors
      including insufficient dissemination and operationalisation of policies and a
      lack of resources. CONCLUSIONS: Mental health policy processes in all four
      countries were inadequate, leading to either weak or non-existent policies, with
      an impact on mental health services. Recommendations are provided to strengthen
      mental health policy processes in these and other African countries.

PMID- 20678206
TI  - Peptides derived from the HIV-1 integrase promote HIV-1 infection and multi
      integration of viral cDNA in LEDGF/p75-knockdown cells.
AB  - BACKGROUND: The presence of the cellular Lens Epithelium Derived Growth Factor
      p75 (LEDGF/p75) protein is essential for integration of the Human
      immunodeficiency virus type 1 (HIV-1) cDNA and for efficient virus production. In
      the absence of LEDGF/p75 very little integration and virus production can be
      detected, as was demonstrated using LEDGF/p75-knockdown cells. RESULTS: Here we
      show that the failure to infect LEDGF/p75-knockdown cells has another reason
      aside from the lack of LEDGF/p75. It is also due to inhibition of the viral
      integrase (IN) enzymatic activity by an early expressed viral Rev protein. The
      formation of an inhibitory Rev-IN complex in virus-infected cells can be
      disrupted by the addition of three IN-derived, cell-permeable peptides,
      designated INr (IN derived-Rev interacting peptides) and INS (IN derived
      integrase stimulatory peptide). The results of the present work confirm previous
      results showing that HIV-1 fails to infect LEDGF/p75-knockdown cells. However, in
      the presence of INrs and INS peptides, relatively high levels of viral cDNA
      integration as well as productive virus infection were obtained following
      infection by a wild type (WT) HIV-1 of LEDGF/p75-knockdown cells. CONCLUSIONS: It
      appears that the lack of integration observed in HIV-1 infected LEDGF/p75
      knockdown cells is due mainly to the inhibitory effect of Rev following the
      formation of a Rev-IN complex. Disruption of this inhibitory complex leads to
      productive infection in those cells.

PMID- 20678207
TI  - Immunological response to highly active antiretroviral therapy following
      treatment for prevention of mother to child transmission of HIV-1: a study in
      Cote d'Ivoire.
AB  - BACKGROUND: Information is currently limited on the long-term follow up of HIV-1
      infected women who are on highly active antiretroviral therapy (HAART) that
      contains nevirapine and lamivudine and who were previously exposed to
      antiretroviral drugs for the prevention of mother to child transmission (PMTCT)
      of HIV. METHODS: We studied the 36-month immunological response to HAART in HIV-1
      infected women in Cote d'Ivoire. The women were previously exposed to
      antiretroviral drug regimens for PMTCT, including single-dose nevirapine and/or
      short-course zidovudine with or without lamivudine. All HAART regimens included a
      non-nucleoside reverse transcriptase inhibitor. RESULTS: At 36 months: the median
      absolute increase in CD4+ T cell count was +359 cells/mm3 (IQR: 210-466) in 200
      women who had undergone 36-month follow-up visits; +359 cells/mm3 (IQR: 222-491)
      in 88 women not exposed to PMTCT antiretrovirals; and +363 cells/mm3 (IQR: 200
      464) in 112 women exposed to at least one antiretroviral PMTCT regimen. Overall,
      49 (19.8%) of the 247 women who initiated HAART met the immunological failure
      criteria at least once during follow up. The overall probability of immunological
      failure was 0.08 (95% CI: 0.12-0.15) at 12 months, and 0.21 (95% CI: 0.16-0.27)
      at 36 months. No difference was observed according to the presence or absence of
      resistance mutations to nevirapine or lamivudine in women tested at four weeks
      postpartum. In addition, at 36 months, 23% of women were lost to follow up, dead
      or had stopped their treatment. CONCLUSIONS: A non-nucleoside reverse
      transcriptase inhibitor-based antiretroviral regimen, initiated a year or more
      after PMTCT exposure and that includes nevirapine, remains a good option for at
      least the first 36 months of treatment.

PMID- 20678208
TI  - Identification and structural characterization of FYVE domain-containing proteins
      of Arabidopsis thaliana.
AB  - BACKGROUND: FYVE domains have emerged as membrane-targeting domains highly
      specific for phosphatidylinositol 3-phosphate (PtdIns(3)P). They are
      predominantly found in proteins involved in various trafficking pathways.
      Although FYVE domains may function as individual modules, dimers or in
      partnership with other proteins, structurally, all FYVE domains share a fold
      comprising two small characteristic double-stranded beta-sheets, and a C-terminal
      alpha-helix, which houses eight conserved Zn2+ ion-binding cysteines. To date,
      the structural, biochemical, and biophysical mechanisms for subcellular targeting
      of FYVE domains for proteins from various model organisms have been worked out
      but plant FYVE domains remain noticeably under-investigated. RESULTS: We carried
      out an extensive examination of all Arabidopsis FYVE domains, including their
      identification, classification, molecular modeling and biophysical
      characterization using computational approaches. Our classification of fifteen
      Arabidopsis FYVE proteins at the outset reveals unique domain architectures for
      FYVE containing proteins, which are not paralleled in other organisms. Detailed
      sequence analysis and biophysical characterization of the structural models are
      used to predict membrane interaction mechanisms previously described for other
      FYVE domains and their subtle variations as well as novel mechanisms that seem to
      be specific to plants. CONCLUSIONS: Our study contributes to the understanding of
      the molecular basis of FYVE-based membrane targeting in plants on a genomic
      scale. The results show that FYVE domain containing proteins in plants have
      evolved to incorporate significant differences from those in other organisms
      implying that they play a unique role in plant signaling pathways and/or play
      similar/parallel roles in signaling to other organisms but use different protein
      players/signaling mechanisms.

PMID- 20678209
TI  - Can AMP induce sputum eosinophils, even in subjects with complete asthma
      remission?
AB  - BACKGROUND: The definition of "clinical asthma remission" is based on absence of
      symptoms and use of medication. However, in the majority of these subjects airway
      inflammation is still present when measured. In the present study we investigated
      whether "complete asthma remission", additionally defined by the absence of
      bronchial hyperresponsiveness (BHR) and the presence of a normal lung function,
      is associated with the absence of airway inflammation. METHODS: Patients with a
      former diagnosis of asthma and a positive histamine provocation test were re
      examined to identify subjects with complete asthma remission (no asthma symptoms
      or medication, PC20 histamine > 32 mg/ml, FEV1 > 90% predicted). Patients with
      PC20 histamine < or = 32 mg/ml were defined as current asthmatics and were
      divided in two groups, i.e. asthmatics with and without BHR to adenosine
      5'monophoshate (AMP). Sputum induction was performed 1 week before and 1 hour
      after AMP provocation. Sputum induction and AMP provocation were previously shown
      to be sensitive markers of airway inflammation. RESULTS: Seven patients met
      criteria for complete asthma remission. Twenty-three were current asthmatics,
      including twelve without hyperresponsiveness to AMP. Subjects with complete
      asthma remission showed no AMP-induced sputum eosinophilia (median (range) 0.2 (0
      - 4.6)% at baseline and 0.2 (0 - 2.6)% after AMP). After AMP, current asthmatics
      had a significant increase in sputum eosinophils (0.5 (0 - 26.0)% at baseline and
      2.6 (0 - 32.0) % after AMP), as had the subgroup of current asthmatics without
      hyperresponsiveness to AMP (0.2 (0 - 1.8)% at baseline and 1.3 (0 - 6.3)% after
      AMP). CONCLUSIONS: Subjects with complete asthma remission, in contrast to
      subjects with current asthma, do not respond with eosinophilic inflammation in
      sputum after AMP provocations. These data lend support to the usefulness of the
      definition of complete asthma remission.

PMID- 20678210
TI  - Adult zebrafish as a model organism for behavioural genetics.
AB  - Recent research has demonstrated the suitability of adult zebrafish to model some
      aspects of complex behaviour. Studies of reward behaviour, learning and memory,
      aggression, anxiety and sleep strongly suggest that conserved regulatory
      processes underlie behaviour in zebrafish and mammals. The isolation and
      molecular analysis of zebrafish behavioural mutants is now starting, allowing the
      identification of novel behavioural control genes. As a result of this, studies
      of adult zebrafish are now helping to uncover the genetic pathways and neural
      circuits that control vertebrate behaviour.

PMID- 20678211
TI  - Fractured metallic tracheostomy tube in a child: a case report and review of the
      literature.
AB  - INTRODUCTION: Tracheostomy is a common airway procedure for life support. The
      fracture of the tracheostomy tube is a rare complication. We report a case of a
      14-year-old boy whose fractured stainless steel tracheostomy tube dislodged into
      the tracheobronchial tree. We include a literature review and proposed
      recommendations for tracheostomy care. CASE PRESENTATION: A 14-year-old Thai boy
      who had a stainless steel tracheostomy tube presented with a complaint of
      intermittent cough for 2 months. During tracheostomy tube cleaning, his parents
      found that the inner tube was missing. A chest X-ray revealed a metallic density
      foreign body in his right main bronchus. He underwent bronchoscopic removal of
      the inner tracheostomy tube and was discharged without further complications.
      CONCLUSION: A fractured tracheostomy tube is a rare complication. Appropriate
      cleaning and scheduled replacement of the tracheostomy tube may prevent this
      complication.

PMID- 20678212
TI  - Fasting hyperglycemia upon hospital admission is associated with higher pneumonia
      complication rates among the elderly.
AB  - BACKGROUND: Hyperglycemia is an independent predictor of adverse outcomes during
      hospitalization. In patients who have pneumonia, significant hyperglycemia is
      associated with poor outcomes. This study evaluates the interaction of the degree
      of hyperglycemia and complication rates stratified by age in non-critically ill
      patients admitted to the hospital for care of community-acquired pneumonia.
      METHODS: Retrospective review of patient records coded for pneumonia. Analysis
      included 501 non-critically ill patients admitted to a tertiary care hospital in
      New York City. Data were stratified by diabetes status, age (less than 65 and 65
      and over), and fasting blood glucose (FBG) within the first 24 hours of
      hospitalization. Among patients with no history of diabetes, FBG was stratified
      as "normal" [FBG </=100 mg/dl (5.6 mmol/l)], "mild-hyperglycemia" [101-125 mg/dl
      (5.7-6.9 mmol/l)], and "severe-hyperglycemia" [>/=126 mg/dl (7 mmol/l)]. The
      diabetic group included known diabetics regardless of FBG. The Pneumonia Severity
      Index (PSI) was calculated for all patients. Complications rates, hospital length
      of stay and mortality were compared among the groups. RESULTS: In patients age 65
      and older, complication rates were 16.7% in normoglycemics, 27.5% in the "mild
      hyperglycemia" group, 28.6% in the "severe hyperglycemia" group, and 25.5% in
      those with known diabetes. The mild and severe-hyperglycemics had similar
      complication rates (p = 0.94). Compared to the normal group, mild and severe
      groups had higher rates of complications, p = 0.05 and p = 0.03, respectively.
      PSI tended to be higher in those over the age of 65. PSI was not significantly
      different when the normal, mild, severe, and known diabetes groups were compared.
      PSI did not predict complications for new hyperglycemia (normals' mean score 87,
      mild 84.7, severe 93.9, diabetics 100). Hospital mortality did not differ among
      groups. Length of stay was longer (p = 0.05) among mild-hyperglycemics (days =
      8.4 s.e. 14.3) vs. normals (days = 6.2 s.e.6.5). CONCLUSION: This study shows
      that FBS between 101-125 mg/dl (5.7-6.9 mmol/l) on hospital admission increases
      pneumonia complication rates among the elderly with no previous diagnosis of
      diabetes.

PMID- 20678213
TI  - Impact of clerkship in the attitudes toward psychiatry among Portuguese medical
      students.
AB  - BACKGROUND: Given the shortage of human resources and the launching of a new
      Mental Health Plan, recruitment of psychiatrists is currently a major concern in
      Portugal, as well as in several other countries. Medical students' attitude
      toward psychiatry has been pointed as a predictor of recruitment. This study aims
      to evaluate the medical students' perception of psychiatry before and after a
      clerkship, and the impact on their intention to pursue psychiatry as a future
      specialty option. METHODS: Two self-report questionnaires were administered to
      all 6th year students in a medical school in Lisbon, before and after a 4-weeks
      full-time psychiatric clerkship, in order to evaluate attitudes toward psychiatry
      and intention to follow psychiatry in the future. Statistical analysis included
      Wilcoxon and Chi-square tests. RESULTS: 153 students (60.8% female) filled in
      both questionnaires (no dropouts). After the clerkship, there was a significant
      improvement regarding the overall merits of psychiatry, efficacy, role definition
      and functioning of psychiatrists, use of legal powers to hospitalize patients and
      specific medical school factors. There was also a significant increase of
      students decided or considering the possibility to take a residency in
      psychiatry.However, perceptions of low prestige and negative pressure from family
      and peers regarding a future choice of psychiatry remained unchanged in about one
      third of the students. CONCLUSIONS: The results indicate clearly that the
      clerkship had a favorable overall impact on the student attitude towards
      psychiatry, as well as in the number of students considering a future career in
      psychiatry. Attitudes toward psychiatry seems a promising outcome indicator of
      the clerkship's quality, but further research is needed in order to assess its
      reliability as a sound predictor of recruitment.

PMID- 20678214
TI  - Subcutaneous emphysema in a case of infective sinusitis: a case report.
AB  - INTRODUCTION: Subcutaneous emphysema with pneumomediastinum is a rare phenomenon
      with a high morbidity and may occur spontaneously. CASE PRESENTATION: A 30-year
      old Caucasian man presented with sudden onset of a painful, swollen neck and was
      found, via clinical and radiological examination to have subcutaneous emphysema.
      A swallow study showed no oesophageal perforation. Computed tomography of his
      neck and thorax demonstrated pneumomediastinum but no other pathology. Management
      was conservative with intravenous antibiotics, fluids and no oral intake. He had
      a history of a productive cough and a flexible nasoendoscopy found purulent
      sinusitis which was treated with topical nasal washes. The patient was discharged
      after 72 hours and will be followed up by the otolaryngology-head and neck
      service. CONCLUSIONS: Infective sinusitis is a rare cause of subcutaneous
      emphysema and pneumomediastinum. It may be managed conservatively provided there
      is early recognition and exclusion of more serious pathology, such as a ruptured
      trachea or oesophagus.

PMID- 20678216
TI  - NU-IN: Nucleotide evolution and input module for the EvolSimulator genome
      simulation platform.
AB  - BACKGROUND: There is increasing demand to test hypotheses that contrast the
      evolution of genes and gene families among genomes, using simulations that work
      across these levels of organization. The EvolSimulator program was developed
      recently to provide a highly flexible platform for forward simulations of amino
      acid evolution in multiple related lineages of haploid genomes, permitting copy
      number variation and lateral gene transfer. Synonymous nucleotide evolution is
      not currently supported, however, and would be highly advantageous for
      comparisons to full genome, transcriptome, and single nucleotide polymorphism
      (SNP) datasets. In addition, EvolSimulator creates new genomes for each
      simulation, and does not allow the input of user-specified sequences and gene
      family information, limiting the incorporation of further biological realism
      and/or user manipulations of the data. FINDINGS: We present modified C++ source
      code for the EvolSimulator platform, which we provide as the extension module NU
      IN. With NU-IN, synonymous and non-synonymous nucleotide evolution is fully
      implemented, and the user has the ability to use real or previously-simulated
      sequence data to initiate a simulation of one or more lineages. Gene family
      membership can be optionally specified, as well as gene retention probabilities
      that model biased gene retention. We provide PERL scripts to assist the user in
      deriving this information from previous simulations. We demonstrate the features
      of NU-IN by simulating genome duplication (polyploidy) in the presence of ongoing
      copy number variation in an evolving lineage. This example is initiated with real
      genomic data, and produces output that we analyse directly with existing
      bioinformatic pipelines. CONCLUSIONS: The NU-IN extension module is a publicly
      available open source software (GNU GPLv3 license) extension to EvolSimulator.
      With the NU-IN module, users are now able to simulate both drift and selection at
      the nucleotide, amino acid, copy number, and gene family levels across sets of
      related genomes, for user-specified starting sequences and associated parameters.
      These features can be used to generate simulated genomic datasets under an
      extremely broad array of conditions, and with a high degree of biological
      realism.

PMID- 20678215
TI  - Distance measurements via the morphogen gradient of Bicoid in Drosophila embryos.
AB  - BACKGROUND: Patterning along the anterior-posterior (A-P) axis in Drosophila
      embryos is instructed by the morphogen gradient of Bicoid (Bcd). Despite
      extensive studies of this morphogen, how embryo geometry may affect gradient
      formation and target responses has not been investigated experimentally. RESULTS:
      In this report, we systematically compare the Bcd gradient profiles and its
      target expression patterns on the dorsal and ventral sides of the embryo. Our
      results support a hypothesis that proper distance measurement and the encoded
      positional information of the Bcd gradient are along the perimeter of the embryo.
      Our results also reveal that the dorsal and ventral sides of the embryo have a
      fundamentally similar relationship between Bcd and its target Hunchback (Hb),
      suggesting that Hb expression properties on the two sides of the embryo can be
      directly traced to Bcd gradient properties. Our 3-D simulation studies show that
      a curvature difference between the two sides of an embryo is sufficient to
      generate Bcd gradient properties that are consistent with experimental
      observations. CONCLUSIONS: The findings described in this report provide a first
      quantitative, experimental evaluation of embryo geometry on Bcd gradient
      formation and target responses. They demonstrate that the physical features of an
      embryo, such as its shape, are integral to how pattern is formed.

PMID- 20678217
TI  - Prevalence and risk factors of vertebral compression fractures in female SLE
      patients.
AB  - INTRODUCTION: Our objective was to determine the frequency of and factors
      associated with prevalent vertebral compression fractures in female systemic
      lupus erythematosus (SLE) patients attending rheumatologists in western Sweden.
      METHODS: In this cross sectional study 150 women were included. They were
      examined with x-ray of thoracic and lumbar spine (Th4 to L4). A reduction of at
      least 20% of any vertebral height, assessed by Genant's semiquantitative method,
      was defined as a fracture. Bone mineral density (BMD) was measured by dual energy
      x-ray absorptiometry (DXA). RESULTS: Median patient age was 47 years (20 to 82)
      and disease duration 11 years (1 to 41). Only 6 (4%) women had a history of
      clinical compressions whereas 43 (29%) had at least one radiological fracture
      each. The patients with at least one fracture at any site were characterized by
      older age (P < 0.001), being postmenopausal (P < 0.01), higher Systemic Lupus
      International Collaborative Clinics Damage Index (P < 0.05), lower BMD total hip
      and femoral neck (P < 0.05), more peripheral fractures (P < 0.01), medication
      with bisphosphonates (P <0.05) and calcium and vitamin D3 (P < 0.05). There were
      no significant differences regarding current or cumulative glucocorticosteroid
      dose between the groups. In logistic regression analyses high age remained as a
      risk factor of at least one vertebral fracture at any site whereas low BMD in
      total hip was associated with vertebral fracture in the lumbar spine.
      CONCLUSIONS: Radiological compression fractures are common but seldom diagnosed
      in SLE patients. High age and low BMD in total hip, but not in spine, was
      associated with vertebral fractures.

PMID- 20678218
TI  - Combined mutations of ASXL1, CBL, FLT3, IDH1, IDH2, JAK2, KRAS, NPM1, NRAS,
      RUNX1, TET2 and WT1 genes in myelodysplastic syndromes and acute myeloid
      leukemias.
AB  - BACKGROUND: Gene mutation is an important mechanism of myeloid leukemogenesis.
      However, the number and combination of gene mutated in myeloid malignancies is
      still a matter of investigation. METHODS: We searched for mutations in the ASXL1,
      CBL, FLT3, IDH1, IDH2, JAK2, KRAS, NPM1, NRAS, RUNX1, TET2 and WT1 genes in 65
      myelodysplastic syndromes (MDSs) and 64 acute myeloid leukemias (AMLs) without
      balanced translocation or complex karyotype. RESULTS: Mutations in ASXL1 and CBL
      were frequent in refractory anemia with excess of blasts. Mutations in TET2
      occurred with similar frequency in MDSs and AMLs and associated equally with
      either ASXL1 or NPM1 mutations. Mutations of RUNX1 were mutually exclusive with
      TET2 and combined with ASXL1 but not with NPM1. Mutations in FLT3 (mutation and
      internal tandem duplication), IDH1, IDH2, NPM1 and WT1 occurred primarily in
      AMLs. CONCLUSION: Only 14% MDSs but half AMLs had at least two mutations in the
      genes studied. Based on the observed combinations and exclusions we classified
      the 12 genes into four classes and propose a highly speculative model that at
      least a mutation in one of each class is necessary for developing AML with simple
      or normal karyotype.

PMID- 20678219
TI  - Effect of a primary health-care-based controlled trial for cardiorespiratory
      fitness in refugee women.
AB  - BACKGROUND: Refugee women have a high risk of coronary heart disease with low
      physical activity as one possible mediator. Furthermore, cultural and
      environmental barriers to increasing physical activity have been demonstrated.
      The aim of the study was to evaluate the combined effect of an approximate 6
      month primary health care- and community-based exercise intervention versus an
      individual written prescription for exercise on objectively assessed
      cardiorespiratory fitness in low-active refugee women. METHODS: A controlled
      clinical trial, named "Support for Increased Physical Activity", was executed
      among 243 refugee women recruited between November 2006 and April 2008 from two
      deprived geographic areas in southern Stockholm, Sweden. One geographic area
      provided the intervention group and the other area the control group. The control
      group was on a higher activity level at both baseline and follow-up, which was
      taken into consideration in the analysis by applying statistical models that
      accounted for this. Relative aerobic capacity and fitness level were assessed as
      the two main outcome measures. RESULTS: The intervention group increased their
      relative aerobic capacity and the percentage with an acceptable fitness level
      (relative aerobic capacity > 23 O2 mlxkgxmin-1) to a greater extent than the
      control group between baseline and the 6-month follow-up, after adjusting for
      possible confounders (P = 0.020). CONCLUSIONS: A combined primary health-care and
      community-based exercise programme (involving non-profit organizations) can be an
      effective strategy to increase cardiorespiratory fitness among low-active refugee
      women. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT00747942.

PMID- 20678220
TI  - 5-FU-hydrogel inhibits colorectal peritoneal carcinomatosis and tumor growth in
      mice.
AB  - BACKGROUND: Colorectal peritoneal carcinomatosis (CRPC) is a common form of
      systemic metastasis of intra-abdominal cancers. Intraperitoneal chemotherapy is a
      preferable option for colorectal cancer. Here we reported that a new system, 5-FU
      loaded hydrogel system, can improve the therapeutic effects of intraperitoneal
      chemotherapy. METHODS: A biodegradable PEG-PCL-PEG (PECE) triblock copolymer was
      successfully synthesized. The biodegradable and temperature sensitive hydrogel
      was developed to load 5-FU. Methylene blue-loaded hydrogel were also developed
      for visible observation of the drug release. The effects and toxicity of the 5-FU
      hydrogel system were evaluated in a murine CRPC model. RESULTS: The hydrogel
      system is an injectable flowing solution at ambient temperature and forms a non
      flowing gel depot at physiological temperature. 5-FU-hydrogel was subsequently
      injected into abdominal cavity in mice with CT26 cancer cells peritoneal
      dissemination. The results showed that the hydrogel delivery system prolonged the
      release of methylene blue; the 5-FU-hydrogel significantly inhibited the
      peritoneal dissemination and growth of CT26 cells. Furthermore, intraperitoneal
      administration of the 5-FU-hydrogel was well tolerated and showed less
      hematologic toxicity. CONCLUSIONS: Our data indicate that the 5-FU-hydrogel
      system can be considered as a new strategy for peritoneal carcinomatosis, and the
      hydrogel may provide a potential delivery system to load different
      chemotherapeutic drugs for peritoneal carcinomatosis of cancers.

PMID- 20678221
TI  - Lack of guanylate cyclase C results in increased mortality in mice following
      liver injury.
AB  - BACKGROUND: Guanylate Cyclase C (GC-C) expression in the intestine plays a role
      in the regulation of fluid and ion transport, as well as epithelial cell
      apoptosis and proliferation. In the adult rat liver, GC-C expression is increased
      in response to injury. We hypothesized that GC-C is required for repair/recovery
      from liver injury. METHODS: We subjected wild type (WT) and GC-C deficient mice
      to acute liver injury with a single injection of the hepatotoxin carbon
      tetrachloride. Changes in the level of expression of GC-C and its ligands
      uroguanylin and guanylin were quantified by real-time PCR. Liver morphology, and
      hepatocyte necrosis, apoptosis and proliferation, were examined at 1-3 days post
      injury in mice on a mixed genetic background. Survival was followed for 14 days
      after carbon tetrachloride injection in wild type and GC-C deficient mice on both
      a mixed genetic background and on an inbred C57BL6/J background. RESULTS: GC-C
      deficient mice on the mixed genetic background nearly all died (median survival
      of 5 days) following carbon tetrachloride injection while WT littermates
      experienced only 35% mortality. Elevated levels of TUNEL-positive hepatocyte
      death on post-injury day 1, increased apoptosis on day 2, and increased areas of
      centrilobular necrosis on days 2 and 3, were evident in livers from GC-C null
      mice compared to WT. Collectively these data suggest increased hepatocyte death
      in the GC-C null mice in the early time period after injury. This corresponds
      temporally with increased expression of GC-C and its ligands guanylin and
      uroguanylin in post-injury WT mouse liver. The hepatocyte proliferative response
      to injury was the same in both genotypes. In contrast, there was no difference in
      survival between GC-C null and WT mice on the inbred C57BL/6 J background in
      response to acute liver injury. CONCLUSIONS: Signalling via GC-C promotes
      hepatocyte survival in vivo and is required for effective recovery from acute
      toxic injury to the liver in a strain-specific manner.

PMID- 20678222
TI  - Persistent sciatica induced by quadratus femoris muscle tear and treated by
      surgical decompression: a case report.
AB  - INTRODUCTION: Quadratus femoris tear is an uncommon injury, which is only rarely
      reported in the literature. In the majority of cases the correct diagnosis is
      delayed due to non-specific symptoms and signs. A magnetic resonance imaging scan
      is crucial in the differential diagnosis since injuries to contiguous soft
      tissues may present with similar symptoms. Presentation with sciatica is not
      reported in the few cases existing in the English literature and the reported
      treatment has always been conservative. CASE PRESENTATION: We report here on a
      case of quadratus femoris tear in a 22-year-old Greek woman who presented with
      persistent sciatica. She was unresponsive to conservative measures and so was
      treated with surgical decompression. CONCLUSION: The correct diagnosis of
      quadratus muscle tear is a challenge for physicians. The treatment is usually
      conservative, but in cases of persistent sciatica surgical decompression is an
      alternative option.

PMID- 20678223
TI  - Redundant causation from a sufficient cause perspective.
AB  - Sufficient causes of disease are redundant when an individual acquires the
      components of two or more sufficient causes. In this circumstance, the individual
      still would have become diseased even if one of the sufficient causes had not
      been acquired. In the context of a study, when any individuals acquire components
      of more than one sufficient cause over the observation period, the etiologic
      effect of the exposure (defined as the absolute or relative difference between
      the proportion of the exposed who develop the disease by the end of the study
      period and the proportion of those individuals who would have developed the
      disease at the moment they did even in the absence of the exposure) may be
      underestimated. Even in the absence of confounding and bias, the observed effect
      estimate represents only a subset of the etiologic effect. This underestimation
      occurs regardless of the measure of effect used.To some extent, redundancy of
      sufficient causes is always present, and under some circumstances, it may make a
      true cause of disease appear to be not causal. This problem is particularly
      relevant when the researcher's goal is to characterize the universe of sufficient
      causes of the disease, identify risk factors for targeted interventions, or
      construct causal diagrams. In this paper, we use the sufficient component cause
      model and the disease response type framework to show how redundant causation
      arises and the factors that determine the extent of its impact on epidemiologic
      effect measures.

PMID- 20678224
TI  - Predicted class-I aminoacyl tRNA synthetase-like proteins in non-ribosomal
      peptide synthesis.
AB  - BACKGROUND: Recent studies point to a great diversity of non-ribosomal peptide
      synthesis systems with major roles in amino acid and co-factor biosynthesis,
      secondary metabolism, and post-translational modifications of proteins by peptide
      tags. The least studied of these systems are those utilizing tRNAs or aminoacyl
      tRNA synthetases (AAtRS) in non-ribosomal peptide ligation. RESULTS: Here we
      describe novel examples of AAtRS related proteins that are likely to be involved
      in the synthesis of widely distributed peptide-derived metabolites. Using
      sensitive sequence profile methods we show that the cyclodipeptide synthases
      (CDPSs) are members of the HUP class of Rossmannoid domains and are likely to be
      highly derived versions of the class-I AAtRS catalytic domains. We also identify
      the first eukaryotic CDPSs in fungi and in animals; they might be involved in
      immune response in the latter organisms. We also identify a paralogous version of
      the methionyl-tRNA synthetase, which is widespread in bacteria, and present
      evidence using contextual information that it might function independently of
      protein synthesis as a peptide ligase in the formation of a peptide- derived
      secondary metabolite. This metabolite is likely to be heavily modified through
      multiple reactions catalyzed by a metal-binding cupin domain and a lysine N6
      monooxygenase that are strictly associated with this paralogous methionyl-tRNA
      synthetase (MtRS). We further identify an analogous system wherein the MtRS has
      been replaced by more typical peptide ligases with the ATP-grasp or modular
      condensation-domains. CONCLUSIONS: The prevalence of these predicted biosynthetic
      pathways in phylogenetically distant, pathogenic or symbiotic bacteria suggests
      that metabolites synthesized by them might participate in interactions with the
      host. More generally, these findings point to a complete spectrum of recruitment
      of AAtRS to various non-ribosomal biosynthetic pathways, ranging from the
      conventional AAtRS, through closely related paralogous AAtRS dedicated to certain
      pathways, to highly derived versions of the class-I AAtRS catalytic domain like
      the CDPSs. Both the conventional AAtRS and their closely related paralogs often
      provide aminoacylated tRNAs for peptide ligations by MprF/Fem/MurM-type
      acetyltransferase fold ligases in the synthesis of peptidoglycan, N-end rule
      modifications of proteins, lipid aminoacylation or biosynthesis of antibiotics,
      such as valinamycin. Alternatively they might supply aminoacylated tRNAs for
      other biosynthetic pathways like that for tetrapyrrole or directly function as
      peptide ligases as in the case of mycothiol and those identified here.

PMID- 20678225
TI  - Roles of KChIP1 in the regulation of GABA-mediated transmission and behavioral
      anxiety.
AB  - K+ channel interacting protein 1 (KChIP1) is a neuronal calcium sensor (NCS)
      protein that interacts with multiple intracellular molecules. Its physiological
      function, however, remains largely unknown. We report that KChIP1 is
      predominantly expressed at GABAergic synapses of a subset of parvalbumin-positive
      neurons in the brain. Forced expression of KChIP1 in cultured hippocampal neurons
      increased the frequency of miniature inhibitory postsynaptic currents (mIPSCs),
      reduced paired pulse facilitation of autaptic IPSCs, and decreases potassium
      current density. Furthermore, genetic ablation of KChIP1 potentiated potassium
      current density in neurons and caused a robust enhancement of anxiety-like
      behavior in mice. Our study suggests that KChIP1 is a synaptic protein that
      regulates behavioral anxiety by modulating inhibitory synaptic transmission, and
      drugs that act on KChIP1 may help to treat patients with mood disorders including
      anxiety.

PMID- 20678226
TI  - Central administration of lipopolysaccharide induces depressive-like behavior in
      vivo and activates brain indoleamine 2,3 dioxygenase in murine organotypic
      hippocampal slice cultures.
AB  - BACKGROUND: Transient stimulation of the innate immune system by an
      intraperitoneal injection of lipopolysaccharide (LPS) activates peripheral and
      central expression of the tryptophan degrading enzyme indoleamine 2,3 dioxygenase
      (IDO) which mediates depressive-like behavior. It is unknown whether direct
      activation of the brain with LPS is sufficient to activate IDO and induce
      depressive-like behavior. METHODS: Sickness and depressive-like behavior in
      C57BL/6J mice were assessed by social exploration and the forced swim test,
      respectively. Expression of cytokines and IDO mRNA was measured by real-time RT
      PCR and cytokine protein was measured by enzyme-linked immunosorbent assays
      (ELISAs). Enzymatic activity of IDO was estimated as the amount of kynurenine
      produced from tryptophan as determined by high pressure liquid chromatography
      (HPLC) with electrochemical detection. RESULTS: Intracerebroventricular (i.c.v.)
      administration of LPS (100 ng) increased steady-state transcripts of TNFalpha, IL
      6 and the inducible isoform of nitric oxide synthase (iNOS) in the hippocampus in
      the absence of any change in IFN gamma mRNA. LPS also increased IDO expression
      and induced depressive-like behavior, as measured by increased duration of
      immobility in the forced swim test. The regulation of IDO expression was
      investigated using in situ organotypic hippocampal slice cultures (OHSCs) derived
      from brains of newborn C57BL/6J mice. In accordance with the in vivo data,
      addition of LPS (10 ng/ml) to the medium of OHSCs induced steady-state expression
      of mRNA transcripts for IDO that peaked at 6 h and translated into increased IDO
      enzymatic activity within 8 h post-LPS. This activation of IDO by direct
      application of LPS was preceded by synthesis and secretion of TNFalpha and IL-6
      protein and activation of iNOS while IFN gamma expression was undetectable.
      CONCLUSION: These data establish that activation of the innate immune system in
      the brain is sufficient to activate IDO and induce depressive-like behavior in
      the absence of detectable IFN gamma. Targeting IDO itself may provide a novel
      therapy for inflammation-associated depression.

PMID- 20678227
TI  - Air pollution exposure during critical time periods in gestation and alterations
      in cord blood lymphocyte distribution: a cohort of livebirths.
AB  - BACKGROUND: Toxic exposures have been shown to influence maturation of the immune
      system during gestation. This study investigates the association between cord
      blood lymphocyte proportions and maternal exposure to air pollution during each
      gestational month. METHODS: Cord blood was analyzed using a FACSort flow
      cytometer to determine proportions of T lymphocytes (CD3+ cells and their
      subsets, CD4+ and CD8+), B lymphocytes (CD19+) and natural killer (NK) cells.
      Ambient air concentrations of 12 polycyclic aromatic hydrocarbons (PAH) and
      particulate matter < 2.5 micrometer in diameter (PM2.5) were measured using fixed
      site monitors. Arithmetic means of these pollutants, calculated for each
      gestational month, were used as exposure metrics. Data on covariates were
      obtained from medical records and questionnaires. Multivariable linear regression
      models were fitted to estimate associations between monthly PAH or PM2.5 and cord
      blood lymphocytes, adjusting for year of birth and district of residence and, in
      further models, gestational season and number of prior live births. RESULTS: The
      adjusted models show significant associations between PAHs or PM2.5 during early
      gestation and increases in CD3+ and CD4+ lymphocytes percentages and decreases in
      CD19+ and NK cell percentages in cord blood. In contrast, exposures during late
      gestation were associated with decreases in CD3+ and CD4+ fractions and increases
      in CD19+ and NK cell fractions. There was no significant association between
      alterations in lymphocyte distribution and air pollution exposure during the mid
      gestation. CONCLUSIONS: PAHs and PM2.5 in ambient air may influence fetal immune
      development via shifts in cord blood lymphocytes distributions. Associations
      appear to differ by exposure in early versus late gestation.

PMID- 20678228
TI  - Automatic de-identification of textual documents in the electronic health record:
      a review of recent research.
AB  - BACKGROUND: In the United States, the Health Insurance Portability and
      Accountability Act (HIPAA) protects the confidentiality of patient data and
      requires the informed consent of the patient and approval of the Internal Review
      Board to use data for research purposes, but these requirements can be waived if
      data is de-identified. For clinical data to be considered de-identified, the
      HIPAA "Safe Harbor" technique requires 18 data elements (called PHI: Protected
      Health Information) to be removed. The de-identification of narrative text
      documents is often realized manually, and requires significant resources. Well
      aware of these issues, several authors have investigated automated de
      identification of narrative text documents from the electronic health record, and
      a review of recent research in this domain is presented here. METHODS: This
      review focuses on recently published research (after 1995), and includes relevant
      publications from bibliographic queries in PubMed, conference proceedings, the
      ACM Digital Library, and interesting publications referenced in already included
      papers. RESULTS: The literature search returned more than 200 publications. The
      majority focused only on structured data de-identification instead of narrative
      text, on image de-identification, or described manual de-identification, and were
      therefore excluded. Finally, 18 publications describing automated text de
      identification were selected for detailed analysis of the architecture and
      methods used, the types of PHI detected and removed, the external resources used,
      and the types of clinical documents targeted. All text de-identification systems
      aimed to identify and remove person names, and many included other types of PHI.
      Most systems used only one or two specific clinical document types, and were
      mostly based on two different groups of methodologies: pattern matching and
      machine learning. Many systems combined both approaches for different types of
      PHI, but the majority relied only on pattern matching, rules, and dictionaries.
      CONCLUSIONS: In general, methods based on dictionaries performed better with PHI
      that is rarely mentioned in clinical text, but are more difficult to generalize.
      Methods based on machine learning tend to perform better, especially with PHI
      that is not mentioned in the dictionaries used. Finally, the issues of
      anonymization, sufficient performance, and "over-scrubbing" are discussed in this
      publication.

PMID- 20678229
TI  - Phylogenetic position of the acariform mites: sensitivity to homology assessment
      under total evidence.
AB  - BACKGROUND: Mites (Acari) have traditionally been treated as monophyletic, albeit
      composed of two major lineages: Acariformes and Parasitiformes. Yet recent
      studies based on morphology, molecular data, or combinations thereof, have
      increasingly drawn their monophyly into question. Furthermore, the usually basal
      (molecular) position of one or both mite lineages among the chelicerates is in
      conflict to their morphology, and to the widely accepted view that mites are
      close relatives of Ricinulei. RESULTS: The phylogenetic position of the acariform
      mites is examined through employing SSU, partial LSU sequences, and morphology
      from 91 chelicerate extant terminals (forty Acariformes). In a static homology
      framework, molecular sequences were aligned using their secondary structure as
      guide, whereby regions of ambiguous alignment were discarded, and pre-aligned
      sequences analyzed under parsimony and different mixed models in a Bayesian
      inference. Parsimony and Bayesian analyses led to trees largely congruent
      concerning infra-ordinal, well-supported branches, but with low support for inter
      ordinal relationships. An exception is Solifugae + Acariformes (P. P = 100%, J. =
      0.91). In a dynamic homology framework, two analyses were run: a standard POY
      analysis and an analysis constrained by secondary structure. Both analyses led to
      largely congruent trees; supporting a (Palpigradi (Solifugae Acariformes)) clade
      and Ricinulei as sister group of Tetrapulmonata with the topology (Ricinulei
      (Amblypygi (Uropygi Araneae))). Combined analysis with two different
      morphological data matrices were run in order to evaluate the impact of
      constraining the analysis on the recovered topology when employing secondary
      structure as a guide for homology establishment. The constrained combined
      analysis yielded two topologies similar to the exclusively molecular analysis for
      both morphological matrices, except for the recovery of Pedipalpi instead of the
      (Uropygi Araneae) clade. The standard (direct optimization) POY analysis,
      however, led to the recovery of trees differing in the absence of the otherwise
      well-supported group Solifugae + Acariformes. CONCLUSIONS: Previous studies
      combining ribosomal sequences and morphology often recovered topologies similar
      to purely morphological analyses of Chelicerata. The apparent stability of
      certain clades not recovered here, like Haplocnemata and Acari, is regarded as a
      byproduct of the way the molecular homology was previously established using the
      instrumentalist approach implemented in POY. Constraining the analysis by a
      priori homology assessment is defended here as a way of maintaining the severity
      of the test when adding new data to the analysis. Although the strength of the
      method advocated here is keeping phylogenetic information from regions usually
      discarded in an exclusively static homology framework; it still has the
      inconvenience of being uninformative on the effect of alignment ambiguity on
      resampling methods of clade support estimation. Finally, putative morphological
      apomorphies of Solifugae + Acariformes are the reduction of the proximal
      cheliceral podomere, medial abutting of the leg coxae, loss of sperm nuclear
      membrane, and presence of differentiated germinative and secretory regions in the
      testis delivering their products into a common lumen.

PMID- 20678230
TI  - Anti-glomerular basement membrane disease superimposed on membranous nephropathy:
      a case report and review of the literature.
AB  - INTRODUCTION: Anti-glomerular basement membrane disease is a rare autoimmune
      disorder characterized by pulmonary hemorrhage, crescentic glomerulonephritis and
      the presence of circulating anti-glomerular basement membrane antibodies. The
      simultaneous occurrence of both anti-glomerular basement membrane disease and
      membranous nephropathy is rare. CASE PRESENTATION: A 59-year-old Hispanic man
      presented with acute onset of nausea and vomiting and was found to have renal
      insufficiency. Work-up included a kidney biopsy, which revealed anti-glomerular
      basement membrane disease with underlying membranous nephropathy. He was treated
      with emergent hemodialysis, intravenous corticosteroids, plasmapheresis, and
      cyclophosphamide without improvement in his renal function. CONCLUSION:
      Simultaneous anti-glomerular basement membrane disease and membranous nephropathy
      is very rare. There have been 16 previous case reports in the English language
      literature that have been associated with a high mortality and morbidity, and a
      very high rate of renal failure resulting in hemodialysis. Co-existence of
      membranous nephropathy and anti-glomerular basement membrane disease may be
      immune-mediated, although the exact mechanism is not clear.

PMID- 20678231
TI  - Hypertensive patients' perceptions of their physicians' knowledge about them: a
      cross-sectional study in Japan.
AB  - BACKGROUND: In order to evaluate the difference in quality of primary care
      provided by physicians between the types of medical institutions in Japan, we
      examined whether the physicians' comprehensive knowledge of their patients is
      perceived differently by the patients seen at clinics and hospitals. METHODS:
      Patients with prescriptions for hypertensive drugs were approached sequentially
      at 13 pharmacies, and were administered a questionnaire on their perception of
      their physician's knowledge about them. Data were obtained for 687 patients (362
      from clinics and 325 from hospitals). A physician's knowledge of his or her
      patients was assessed according to six aspects: their medical history, their
      current medications, history of allergy, what worries patients most about their
      health, patients' values and beliefs on their health, and patients' roles and
      responsibilities at work, home, or school. Responses were scored from 1 through 6
      (1: knows very well; 6: doesn't know at all). RESULTS: Patients treated in
      clinics were seen more frequently, for a longer period, and had fewer
      complications than the patients who were treated in hospitals. Among the six
      aspects of physicians' knowledge assessed, 79.3% of the patients reported that
      their physicians knew their complete list of medications "very well or well,"
      while 28.3% reported the same about their roles and responsibilities at work,
      home, or school. Physicians in clinics were considered to know their patients'
      worries about their health (p = 0.004) and the roles and responsibilities of the
      patients at work, home, or school (p = 0.028) well. Multiple regression analysis
      showed that the type of medical institutions remained as a significant variable
      only for the aspect of patients' worries about their health. The factor that
      consistently affected the patients' perception of physicians' knowledge about
      them was the patients' age. CONCLUSIONS: Hypertensive patients' perceptions of
      their physicians' knowledge about them did not differ significantly between
      clinics and hospitals in Japan for most of the aspects. In order to differentiate
      the roles of physicians in hospitals and clinics better and ensure the quality of
      primary care, the establishment of a standardized educational system to train
      primary care physicians better is recommended.

PMID- 20678232
TI  - Characterization of alphasatellites associated with monopartite
      begomovirus/betasatellite complexes in Yunnan, China.
AB  - BACKGROUND: Alphasatellites are single-stranded molecules that are associated
      with monopartite begomovirus/betasatellite complexes. RESULTS: Alphasatellites
      were identified in begomovirus-infected plant samples in Yunnan, China. All
      samples that contained alphasatellites also contained betasatellites, but only
      some samples that contained betasatellites contained alphasatellites. Thirty
      three alphasatellites were sequenced, and they ranged from 1360 to 1376
      nucleotides. All alphasatellites contain 3 conserved features: a single open
      reading frame (Rep), a conserved hairpin structure, and an adenine-rich (A-rich)
      region. On the basis of the phylogenetic tree of the complete nucleotide
      sequences, the alphasatellites were divided into 3 types with one exception. Type
      1 was associated with Tomato yellow leaf curl China virus (TYLCCNV)/Tomato yellow
      leaf curl China betasatellite (TYLCCNB) complex. Type 2 was associated with
      Tobacco curly shoot virus (TbCSV)/Tobacco curly shoot betasatellite (TbCSB)
      complex. Type 3 was associated with TbCSV/Ageratum yellow vein betasatellite
      (AYVB) complex. Within each type, nucleotide sequence identity ranged from 83.4
      to 99.7%, while 63.4-81.3% identity was found between types. Mixed infections of
      alphasatellites associated with begomovirus/betasatellite complexes were
      documented. CONCLUSIONS: Our results validate that alphasatellites are only
      associated with begomovirus/betasatellite complexes. Thirty-three sequenced
      alphasatellites isolated from Yunnan Province, China were divided into 3 types-
      each associated with a specific begomovirus/betasatellite complex. Mix-infections
      of alphasatellite molecules may not be unusual.

PMID- 20678233
TI  - Living Well with Diabetes: a randomized controlled trial of a telephone-delivered
      intervention for maintenance of weight loss, physical activity and glycaemic
      control in adults with type 2 diabetes.
AB  - BACKGROUND: By 2025, it is estimated that approximately 1.8 million Australian
      adults (approximately 8.4% of the adult population) will have diabetes, with the
      majority having type 2 diabetes. Weight management via improved physical activity
      and diet is the cornerstone of type 2 diabetes management. However, the majority
      of weight loss trials in diabetes have evaluated short-term, intensive clinic
      based interventions that, while producing short-term outcomes, have failed to
      address issues of maintenance and broad population reach. Telephone-delivered
      interventions have the potential to address these gaps. METHODS/DESIGN: Using a
      two-arm randomised controlled design, this study will evaluate an 18-month,
      telephone-delivered, behavioural weight loss intervention focussing on physical
      activity, diet and behavioural therapy, versus usual care, with follow-up at 24
      months. Three-hundred adult participants, aged 20-75 years, with type 2 diabetes,
      will be recruited from 10 general practices via electronic medical records
      search. The Social-Cognitive Theory driven intervention involves a six-month
      intensive phase (4 weekly calls and 11 fortnightly calls) and a 12-month
      maintenance phase (one call per month). Primary outcomes, assessed at 6, 18 and
      24 months, are: weight loss, physical activity, and glycaemic control (HbA1c),
      with weight loss and physical activity also measured at 12 months. Incremental
      cost-effectiveness will also be examined. Study recruitment began in February
      2009, with final data collection expected by February 2013. DISCUSSION: This is
      the first study to evaluate the telephone as the primary method of delivering a
      behavioural weight loss intervention in type 2 diabetes. The evaluation of
      maintenance outcomes (6 months following the end of intervention), the use of
      accelerometers to objectively measure physical activity, and the inclusion of a
      cost-effectiveness analysis will advance the science of broad reach approaches to
      weight control and health behaviour change, and will build the evidence base
      needed to advocate for the translation of this work into population health
      practice. TRIAL REGISTRATION: ACTRN12608000203358.

PMID- 20678234
TI  - The exenatide analogue AC3174 attenuates hypertension, insulin resistance, and
      renal dysfunction in Dahl salt-sensitive rats.
AB  - BACKGROUND: Activation of glucagon-like peptide-1 (GLP-1) receptors improves
      insulin sensitivity and induces vasodilatation and diuresis. AC3174 is a peptide
      analogue with pharmacologic properties similar to the GLP-1 receptor agonist,
      exenatide. Hypothetically, chronic AC3174 treatment could attenuate salt-induced
      hypertension, cardiac morbidity, insulin resistance, and renal dysfunction in
      Dahl salt-sensitive (DSS) rats. METHODS: DSS rats were fed low salt (LS, 0.3%
      NaCl) or high salt (HS, 8% NaCl) diets. HS rats were treated with vehicle, AC3174
      (1.7 pmol/kg/min), or GLP-1 (25 pmol/kg/min) for 4 weeks via subcutaneous
      infusion. Other HS rats received captopril (150 mg/kg/day) or AC3174 plus
      captopril. RESULTS: HS rat survival was improved by all treatments except GLP-1.
      Systolic blood pressure (SBP) was lower in LS rats and in GLP-1, AC3174,
      captopril, or AC3174 plus captopril HS rats than in vehicle HS rats (p < 0.05).
      AC3174 plus captopril attenuated the deleterious effects of high salt on
      posterior wall thickness, LV mass, and the ratio of LV mass to body weight (P <
      or = 0.05). In contrast, GLP-1 had no effect on these cardiovascular parameters.
      All treatments reduced LV wall stress. GLP-1, AC3174, captopril, or AC3174 plus
      captopril normalized fasting insulin and HOMA-IR (P < or = 0.05). AC3174,
      captopril, or AC3174 plus captopril improved renal function (P < or = 0.05).
      Renal morphology in HS rats was associated with extensive sclerosis. Monotherapy
      with AC3174, captopril, or GLP-1 attenuated renal damage. However, AC3174 plus
      captopril produced the most effective improvement. CONCLUSIONS: Thus, AC3174 had
      antihypertensive, cardioprotective, insulin-sensitizing, and renoprotective
      effects in the DSS hypertensive rat model. Furthermore, AC3174 improved animal
      survival, an effect not observed with GLP-1.

PMID- 20678235
TI  - Screening for pre-clinical disability in different residential settings.
AB  - BACKGROUND: Preventing disability and offering effective interventions to older
      people during early decline in function is most likely to be effective if those
      most at risk of progressive disablement are able to be identified. Similarly the
      ability to easily identify a group with similar functional profile from disparate
      sectors of the community is of significant benefit to researchers. This study
      aimed to (1) describe the use of a pre-clinical disability screening tool to
      select a functionally comparable group of older men and women with early
      functional limitation from different settings, and (2) explore factors associated
      with function and disability. METHODS: Self-reported function and disability
      measured with the Late-Life Function and Disability Instrument along with a range
      of physical performance measurements were compared across residential settings
      and gender in a sample of 471 trial participants identified as pre-clinically
      disabled after being screened with the Fried pre-clinical disability tool.
      Factors that might lie on the pathway to progressive disablement were identified
      using multiple linear regression analysis. RESULTS: We found that a sample
      population, screened for pre-clinical disability, had a functional status and
      disability profile reflecting early functional limitation, regardless of
      residential setting or gender. Statistical models identified a range of factors
      associated with function and disability which explained a greater degree of the
      variation in function, than disability. CONCLUSIONS: We selected a group of
      people with a comparable function and disability profile, consistent with the pre
      clinical stage of disability, from a sample of older Australian men and women
      from different residential settings using the Fried pre-clinical disability
      screening tool. The results suggest that the screening tool can be used with
      greater confidence for research, clinical and population health purposes. Further
      research is required to examine the validity of the tool. These findings offer
      insight into the type of impairment factors characterising early functional loss
      that could be addressed through disability prevention initiatives. TRIAL
      REGISTRATION: ACTRN01206000431527.

PMID- 20678236
TI  - Using paired-end sequences to optimise parameters for alignment of sequence reads
      against related genomes.
AB  - BACKGROUND: The advent of cheap high through-put sequencing methods has
      facilitated low coverage skims of a large number of organisms. To maximise the
      utility of the sequences, assembly into contigs and then ordering of those
      contigs is required. Whilst sequences can be assembled into contigs de novo,
      using assembled genomes of closely related organisms as a framework can
      considerably aid the process. However, the preferred search programs and
      parameters that will optimise the sensitivity and specificity of the alignments
      between the sequence reads and the framework genome(s) are not necessarily
      obvious. Here we demonstrate a process that uses paired-end sequence reads to
      choose an optimal program and alignment parameters. RESULTS: Unlike two single
      fragment reads, in paired-end sequence reads, such as BAC-end sequences, the two
      sequences in the pair have a known positional relationship in the original
      genome. This provides an additional level of confidence over match scores and e
      values in the accuracy of the positional assignment of the reads in the
      comparative genome. Three commonly used sequence alignment programs: MegaBLAST,
      Blastz and PatternHunter were used to align a set of ovine BAC-end sequences
      against the equine genome assembly. A range of different search parameters, with
      a particular focus on contiguous and discontiguous seeds, were used for each
      program. The number of reads with a hit and the number of read pairs with hits
      for the two end sequences in the tail-to-tail paired-end configuration were
      plotted relative to the theoretical maximum expected curve. Of the programs
      tested, MegaBLAST with short contiguous seed lengths (word size 8-11) performed
      best in this particular task. In addition the data also provides estimates of the
      false positive and false negative rates, which can be used to determine the
      appropriate values of additional parameters, such as score cut-off, to balance
      sensitivity and specificity. To determine whether the approach also worked for
      the alignment of shorter reads, the first 240 bases of each BAC end sequence were
      also aligned to the equine genome. Again, contiguous MegaBLAST performed the best
      in optimising the sensitivity and specificity with which sheep BAC end reads map
      to the equine and bovine genomes. CONCLUSIONS: Paired-end reads, such as BAC-end
      sequences, provide an efficient mechanism to optimise sequence alignment
      parameters, for example for comparative genome assemblies, by providing an
      objective standard to evaluate performance.

PMID- 20678237
TI  - Comparison study of microarray meta-analysis methods.
AB  - BACKGROUND: Meta-analysis methods exist for combining multiple microarray
      datasets. However, there are a wide range of issues associated with microarray
      meta-analysis and a limited ability to compare the performance of different meta
      analysis methods. RESULTS: We compare eight meta-analysis methods, five existing
      methods, two naive methods and a novel approach (mDEDS). Comparisons are
      performed using simulated data and two biological case studies with varying
      degrees of meta-analysis complexity. The performance of meta-analysis methods is
      assessed via ROC curves and prediction accuracy where applicable. CONCLUSIONS:
      Existing meta-analysis methods vary in their ability to perform successful meta
      analysis. This success is very dependent on the complexity of the data and type
      of analysis. Our proposed method, mDEDS, performs competitively as a meta
      analysis tool even as complexity increases. Because of the varying abilities of
      compared meta-analysis methods, care should be taken when considering the meta
      analysis method used for particular research.

PMID- 20678238
TI  - Structural motif screening reveals a novel, conserved carbohydrate-binding
      surface in the pathogenesis-related protein PR-5d.
AB  - BACKGROUND: Aromatic amino acids play a critical role in protein-glycan
      interactions. Clusters of surface aromatic residues and their features may
      therefore be useful in distinguishing glycan-binding sites as well as predicting
      novel glycan-binding proteins. In this work, a structural bioinformatics approach
      was used to screen the Protein Data Bank (PDB) for coplanar aromatic motifs
      similar to those found in known glycan-binding proteins. RESULTS: The proteins
      identified in the screen were significantly associated with carbohydrate-related
      functions according to gene ontology (GO) enrichment analysis, and predicted
      motifs were found frequently within novel folds and glycan-binding sites not
      included in the training set. In addition to numerous binding sites predicted in
      structural genomics proteins of unknown function, one novel prediction was a
      surface motif (W34/W36/W192) in the tobacco pathogenesis-related protein, PR-5d.
      Phylogenetic analysis revealed that the surface motif is exclusive to a subfamily
      of PR-5 proteins from the Solanaceae family of plants, and is absent completely
      in more distant homologs. To confirm PR-5d's insoluble-polysaccharide binding
      activity, a cellulose-pulldown assay of tobacco proteins was performed and PR-5d
      was identified in the cellulose-binding fraction by mass spectrometry.
      CONCLUSIONS: Based on the combined results, we propose that the putative binding
      site in PR-5d may be an evolutionary adaptation of Solanaceae plants including
      potato, tomato, and tobacco, towards defense against cellulose-containing
      pathogens such as species of the deadly oomycete genus, Phytophthora. More
      generally, the results demonstrate that coplanar aromatic clusters on protein
      surfaces are a structural signature of glycan-binding proteins, and can be used
      to computationally predict novel glycan-binding proteins from 3 D structure.

PMID- 20678239
TI  - Sampling strategies to measure the prevalence of common recurrent infections in
      longitudinal studies.
AB  - BACKGROUND: Measuring recurrent infections such as diarrhoea or respiratory
      infections in epidemiological studies is a methodological challenge. Problems in
      measuring the incidence of recurrent infections include the episode definition,
      recall error, and the logistics of close follow up. Longitudinal prevalence (LP),
      the proportion-of-time-ill estimated by repeated prevalence measurements, is an
      alternative measure to incidence of recurrent infections. In contrast to
      incidence which usually requires continuous sampling, LP can be measured at
      intervals. This study explored how many more participants are needed for
      infrequent sampling to achieve the same study power as frequent sampling.
      METHODS: We developed a set of four empirical simulation models representing low
      and high risk settings with short or long episode durations. The model was used
      to evaluate different sampling strategies with different assumptions on recall
      period and recall error. RESULTS: The model identified three major factors that
      influence sampling strategies: (1) the clustering of episodes in individuals; (2)
      the duration of episodes; (3) the positive correlation between an individual's
      disease incidence and episode duration. Intermittent sampling (e.g. 12 times per
      year) often requires only a slightly larger sample size compared to continuous
      sampling, especially in cluster-randomized trials. The collection of period
      prevalence data can lead to highly biased effect estimates if the exposure
      variable is associated with episode duration. To maximize study power, recall
      periods of 3 to 7 days may be preferable over shorter periods, even if this leads
      to inaccuracy in the prevalence estimates. CONCLUSION: Choosing the optimal
      approach to measure recurrent infections in epidemiological studies depends on
      the setting, the study objectives, study design and budget constraints. Sampling
      at intervals can contribute to making epidemiological studies and trials more
      efficient, valid and cost-effective.

PMID- 20678240
TI  - Minimal important differences and response shift in health-related quality of
      life; a longitudinal study in patients with multiple myeloma.
AB  - BACKGROUND: We previously reported that changes of 6-17 percent in the EORTC QLQ
      C30 scores are regarded important by patients with multiple myeloma and thus may
      be considered as Minimal Important Differences (MIDs). However, patients'
      internal standard of measurement may have changed over time (response shift, RS).
      In the present work, we evaluated whether myeloma patients experience RS and if
      this could affect the MID-estimates. METHODS: Between 2006 and 2008, 239 patients
      with multiple myeloma completed the EORTC QLQ-C30 at baseline (T1) and after
      three months (T2). At T2, patients were asked if they had noticed any change in
      the domains pain, fatigue, physical function and global quality of life. They
      were also asked to give a retrospective judgment of their baseline values on all
      the four domains. RESULTS: We found clear evidence of RS in myeloma patients.
      However, there were differences in both magnitude and direction between patients
      who stated that they improved and those who deteriorated. Deteriorating patients
      retrospectively reported better health-related quality of life at T1 for the
      domains pain, fatigue and physical function. In these patients, MIDs adjusted for
      RS were observed to increase up to 12 percentage points. In contrast, for
      patients stating that they improved, we only found evidence of statistically
      significant RS in the domain global quality of life. CONCLUSIONS: MIDs estimated
      from pre-test/post-test data appeared to be robust against RS in patients
      reporting improvement over 3-months. This could indicate that RS has a minimal
      impact on the results in patients who respond to treatment, and that RS may not
      have an important impact on interpretation of changes reported in clinical trials
      where an improvement occurs.Although the effect sizes of the RSs were small, RS
      in deteriorating patients may have an important impact on the interpretation of
      changes reported in clinical trials.

PMID- 20678241
TI  - Comprehensive transcriptome analysis of mouse embryonic stem cell adipogenesis
      unravels new processes of adipocyte development.
AB  - BACKGROUND: The current epidemic of obesity has caused a surge of interest in the
      study of adipose tissue formation. While major progress has been made in defining
      the molecular networks that control adipocyte terminal differentiation, the early
      steps of adipocyte development and the embryonic origin of this lineage remain
      largely unknown. RESULTS: Here we performed genome-wide analysis of gene
      expression during adipogenesis of mouse embryonic stem cells (ESCs). We then
      pursued comprehensive bioinformatic analyses, including de novo functional
      annotation and curation of the generated data within the context of biological
      pathways, to uncover novel biological functions associated with the early steps
      of adipocyte development. By combining in-depth gene regulation studies and in
      silico analysis of transcription factor binding site enrichment, we also provide
      insights into the transcriptional networks that might govern these early steps.
      CONCLUSIONS: This study supports several biological findings: firstly, adipocyte
      development in mouse ESCs is coupled to blood vessel morphogenesis and neural
      development, just as it is during mouse development. Secondly, the early steps of
      adipocyte formation involve major changes in signaling and transcriptional
      networks. A large proportion of the transcription factors that we uncovered in
      mouse ESCs are also expressed in the mouse embryonic mesenchyme and in adipose
      tissues, demonstrating the power of our approach to probe for genes associated
      with early developmental processes on a genome-wide scale. Finally, we reveal a
      plethora of novel candidate genes for adipocyte development and present a unique
      resource that can be further explored in functional assays.

PMID- 20678242
TI  - Molecular diversity of Mycobacterium tuberculosis isolates from patients with
      tuberculosis in Honduras.
AB  - BACKGROUND: Tuberculosis persists as a public health problem in Honduras. A
      better knowledge of the molecular characteristics of Mycobacterium tuberculosis
      strains will contribute to understand the transmission dynamics of the disease
      within the country. The aim of this study was to provide an insight of the
      genetic biodiversity of M. tuberculosis clinical isolates collected in Honduras
      between 1994 and 2002. Genotyping was performed using spoligotyping and RFLP. The
      spoligotypes obtained were compared with the SITVIT2 proprietary database of the
      Pasteur Institute of Guadeloupe. RESULTS: Spoligotyping grouped 84% of the
      isolates into 27 clusters (2 to 43 strains per cluster). Of the 44 shared
      international types (SITs) identified among the Honduran stains, 8 SITs were
      newly identified either within the present study or after match with an orphan
      type previously identified in the SITVIT2 database. In addition, 16 patterns
      corresponded to orphan, previously unreported isolates.The Latin American
      Mediterranean (LAM) lineage was the most common in this study; 55% of the strains
      belonged to this family. Other genotypes found were Haarlem (16%), T (16%), X
      clade (6%), Unknown signature (5%) and S (1%). Only one Beijing strain was
      identified (0.5%).We observed a high degree of diversity after characterizing the
      43 isolates belonging to the main spoligotyping cluster (SIT 33, LAM3) with
      IS6110-RFLP. A total of 35 different RFLP-fingerprints were detected, of which 6
      patterns corresponded to the same number of clusters comprising 14 strains.
      CONCLUSIONS: The findings obtained in this study show that tuberculosis
      transmission in Honduras is due to modern M. tuberculosis lineages with high
      level of biodiversity.

PMID- 20678243
TI  - Assessing the impact of a combined analysis of four common low-risk genetic
      variants on autism risk.
AB  - BACKGROUND: Autism is a complex disorder characterized by deficits involving
      communication, social interaction, and repetitive and restrictive patterns of
      behavior. Twin studies have shown that autism is strongly heritable, suggesting a
      strong genetic component. In other disease states with a complex etiology, such
      as type 2 diabetes, cancer and cardiovascular disease, combined analysis of
      multiple genetic variants in a genetic score has helped to identify individuals
      at high risk of disease. Genetic scores are designed to test for association of
      genetic markers with disease. METHOD: The accumulation of multiple risk alleles
      markedly increases the risk of being affected, and compared with studying
      polymorphisms individually, it improves the identification of subgroups of
      individuals at greater risk. In the present study, we show that this approach can
      be applied to autism by specifically looking at a high-risk population of
      children who have siblings with autism. A two-sample study design and the
      generation of a genetic score using multiple independent genes were used to
      assess the risk of autism in a high-risk population. RESULTS: In both samples,
      odds ratios (ORs) increased significantly as a function of the number of risk
      alleles, with a genetic score of 8 being associated with an OR of 5.54 (95%
      confidence interval [CI] 2.45 to 12.49). The sensitivities and specificities for
      each genetic score were similar in both analyses, and the resultant area under
      the receiver operating characteristic curves were identical (0.59). CONCLUSIONS:
      These results suggest that the accumulation of multiple risk alleles in a genetic
      score is a useful strategy for assessing the risk of autism in siblings of
      affected individuals, and may be better than studying single polymorphisms for
      identifying subgroups of individuals with significantly greater risk.

PMID- 20678244
TI  - Molecular Autism: accelerating and integrating research into neurodevelopmental
      conditions.

PMID- 20678245
TI  - Paternal age increases the risk for autism in an Iranian population sample.
AB  - BACKGROUND: Autism is a neurodevelopmental disorder which is known to have a
      strong genetic component and is most likely oligogenic. However, the necessary
      role of environmental factors has been well documented. Prior research suggests
      that parental characteristics, such as age and level of education, may be
      associated with a risk of autism. Parental age has been shown to be associated
      with many disorders, such as schizophrenia, childhood cancer and fetal death.
      However, results from studies of parental age and autism are inconsistent.
      METHODS: In the present study, we investigated the association of autism with
      parental age in 179 autism cases and 1611 matched cohort children from Iran. Each
      case was matched with nine cohort controls on parental education, sex, order of
      birth, consanguineous marriage, urbanism and province of residence. The Cox
      regression model was used to carry out conditional logistic regression on the
      matched data. RESULTS: There was a significant association between higher
      paternal age, but not maternal age, and an increasing risk of autism. An analysis
      of the combined effect of parental age and education also revealed that parents
      with higher education had an increased risk of having autistic children, with a
      dose-response effect of parental age. CONCLUSIONS: This study, which is the first
      epidemiological study of autism in Iran, provides evidence of the association of
      paternal age and risk of autism.

PMID- 20678246
TI  - Genome-wide linkage analyses of two repetitive behavior phenotypes in Utah
      pedigrees with autism spectrum disorders.
AB  - BACKGROUND: It has been suggested that efforts to identify genetic risk markers
      of autism spectrum disorder (ASD) would benefit from the analysis of more
      narrowly defined ASD phenotypes. Previous research indicates that 'insistence on
      sameness' (IS) and 'repetitive sensory-motor actions' (RSMA) are two factors
      within the ASD 'repetitive and stereotyped behavior' domain. The primary aim of
      this study was to identify genetic risk markers of both factors to allow
      comparison of those markers with one another and with markers found in the same
      set of pedigrees using ASD diagnosis as the phenotype. Thus, we empirically
      addresses the possibilities that more narrowly defined phenotypes improve linkage
      analysis signals and that different narrowly defined phenotypes are associated
      with different loci. Secondary aims were to examine the correlates of IS and RSMA
      and to assess the heritability of both scales. METHODS: A genome-wide linkage
      analysis was conducted with a sample of 70 multiplex ASD pedigrees using IS and
      RSMA as phenotypes. Genotyping services were provided by the Center for Inherited
      Disease Research using the 6 K single nucleotide polymorphism linkage panel.
      Analysis was done using the multipoint linkage software program MCLINK, a Markov
      chain Monte Carlo (MCMC) method that allows for multilocus linkage analysis on
      large extended pedigrees. RESULTS: Genome-wide significance was observed for IS
      at 2q37.1-q37.3 (dominant model heterogeneity lod score (hlod) 3.42) and for RSMA
      at 15q13.1-q14 (recessive model hlod 3.93). We found some linkage signals that
      overlapped and others that were not observed in our previous linkage analysis of
      the ASD phenotype in the same pedigrees, and regions varied in the range of
      phenotypes with which they were linked. A new finding with respect to IS was that
      it is positively associated with IQ if the IS-RSMA correlation is statistically
      controlled. CONCLUSIONS: The finding that IS and RSMA are linked to different
      regions that only partially overlap regions previously identified with ASD as the
      phenotype supports the value of including multiple, narrowly defined phenotypes
      in ASD genetic research. Further, we replicated previous reports indicating that
      RSMA is more strongly associated than IS with measures of ASD severity.

PMID- 20678247
TI  - A large-scale survey of the novel 15q24 microdeletion syndrome in autism spectrum
      disorders identifies an atypical deletion that narrows the critical region.
AB  - BACKGROUND: The 15q24 microdeletion syndrome has been recently described as a
      recurrent, submicroscopic genomic imbalance found in individuals with
      intellectual disability, typical facial appearance, hypotonia, and digital and
      genital abnormalities. Gene dosage abnormalities, including copy number
      variations (CNVs), have been identified in a significant fraction of individuals
      with autism spectrum disorders (ASDs). In this study we surveyed two ASD cohorts
      for 15q24 abnormalities to assess the frequency of genomic imbalances in this
      interval. METHODS: We screened 173 unrelated subjects with ASD from the Central
      Valley of Costa Rica and 1336 subjects with ASD from 785 independent families
      registered with the Autism Genetic Resource Exchange (AGRE) for CNVs across 15q24
      using oligonucleotide arrays. Rearrangements were confirmed by array comparative
      genomic hybridization and quantitative PCR. RESULTS: Among the patients from
      Costa Rica, an atypical de novo deletion of 3.06 Mb in 15q23-q24.1 was detected
      in a boy with autism sharing many features with the other 13 subjects with the
      15q24 microdeletion syndrome described to date. He exhibited intellectual
      disability, constant smiling, characteristic facial features (high anterior
      hairline, broad medial eyebrows, epicanthal folds, hypertelorism, full lower lip
      and protuberant, posteriorly rotated ears), single palmar crease, toe syndactyly
      and congenital nystagmus. The deletion breakpoints are atypical and lie outside
      previously characterized low copy repeats (69,838-72,897 Mb). Genotyping data
      revealed that the deletion had occurred in the paternal chromosome. Among the
      AGRE families, no large 15q24 deletions were observed. CONCLUSIONS: From the
      current and previous studies, deletions in the 15q24 region represent rare causes
      of ASDs with an estimated frequency of 0.1 to 0.2% in individuals ascertained for
      ASDs, although the proportion might be higher in sporadic cases. These rates
      compare with a frequency of about 0.3% in patients ascertained for unexplained
      intellectual disability and congenital anomalies. This atypical deletion reduces
      the minimal interval for the syndrome from 1.75 Mb to 766 kb, implicating a
      reduced number of genes (15 versus 38). Sequencing of genes in the 15q24 interval
      in large ASD and intellectual disability samples may identify mutations of
      etiologic importance in the development of these disorders.

PMID- 20678248
TI  - Genetics in psychiatry: common variant association studies.
AB  - Many psychiatric conditions and traits are associated with significant
      heritability. Genetic risk for psychiatric conditions encompass rare variants,
      identified due to major effect, as well as common variants, the latter analyzed
      by association analyses. We review guidelines for common variant association
      analyses, undertaking after assessing evidence of heritability. We highlight the
      importance of: suitably large sample sizes; an experimental design that controls
      for ancestry; careful data cleaning; correction for multiple testing; small P
      values for positive findings; assessment of effect size for positive findings;
      and, inclusion of an independent replication sample. We also note the importance
      of a critical discussion of any prior findings, biological follow-up where
      possible, and a means of accessing the raw data.

PMID- 20678249
TI  - Polymorphisms in leucine-rich repeat genes are associated with autism spectrum
      disorder susceptibility in populations of European ancestry.
AB  - BACKGROUND: Autism spectrum disorders (ASDs) are a group of highly heritable
      neurodevelopmental disorders which are characteristically comprised of
      impairments in social interaction, communication and restricted
      interests/behaviours. Several cell adhesion transmembrane leucine-rich repeat
      (LRR) proteins are highly expressed in the nervous system and are thought to be
      key regulators of its development. Here we present an association study analysing
      the roles of four promising candidate genes - LRRTM1 (2p), LRRTM3 (10q), LRRN1
      (3p) and LRRN3 (7q) - in order to identify common genetic risk factors underlying
      ASDs. METHODS: In order to gain a better understanding of how the genetic
      variation within these four gene regions may influence susceptibility to ASDs, a
      family-based association study was undertaken in 661 families of European
      ancestry selected from four different ASD cohorts. In addition, a case-control
      study was undertaken across the four LRR genes, using logistic regression in
      probands with ASD of each population against 295 ECACC controls. RESULTS:
      Significant results were found for LRRN3 and LRRTM3 (P < 0.005), using both
      single locus and haplotype approaches. These results were further supported by a
      case-control analysis, which also highlighted additional SNPs in LRRTM3.
      CONCLUSIONS: Overall, our findings implicate the neuronal leucine-rich genes
      LRRN3 and LRRTM3 in ASD susceptibility.

PMID- 20678250
TI  - Genome-wide linkage using the Social Responsiveness Scale in Utah autism
      pedigrees.
AB  - BACKGROUND: Autism Spectrum Disorders (ASD) are phenotypically heterogeneous,
      characterized by impairments in the development of communication and social
      behaviour and the presence of repetitive behaviour and restricted interests.
      Dissecting the genetic complexity of ASD may require phenotypic data reflecting
      more detail than is offered by a categorical clinical diagnosis. Such data are
      available from the Social Responsiveness Scale (SRS) which is a continuous,
      quantitative measure of social ability giving scores that range from significant
      impairment to above average ability. METHODS: We present genome-wide results for
      64 multiplex and extended families ranging from two to nine generations. SRS
      scores were available from 518 genotyped pedigree subjects, including affected
      and unaffected relatives. Genotypes from the Illumina 6 k single nucleotide
      polymorphism panel were provided by the Center for Inherited Disease Research.
      Quantitative and qualitative analyses were done using MCLINK, a software package
      that uses Markov chain Monte Carlo (MCMC) methods to perform multilocus linkage
      analysis on large extended pedigrees. RESULTS: When analysed as a qualitative
      trait, linkage occurred in the same locations as in our previous affected-only
      genome scan of these families, with findings on chromosomes 7q31.1-q32.3
      [heterogeneity logarithm of the odds (HLOD) = 2.91], 15q13.3 (HLOD = 3.64), and
      13q12.3 (HLOD = 2.23). Additional positive qualitative results were seen on
      chromosomes 6 and 10 in regions that may be of interest for other
      neuropsychiatric disorders. When analysed as a quantitative trait, results
      replicated a peak found in an independent sample using quantitative SRS scores on
      chromosome 11p15.1-p15.4 (HLOD = 2.77). Additional positive quantitative results
      were seen on chromosomes 7, 9, and 19. CONCLUSIONS: The SRS linkage peaks
      reported here substantially overlap with peaks found in our previous affected
      only genome scan of clinical diagnosis. In addition, we replicated a previous SRS
      peak in an independent sample. These results suggest the SRS is a robust and
      useful phenotype measure for genetic linkage studies of ASD. Finally, analyses of
      SRS scores revealed linkage peaks overlapping with evidence from other studies of
      neuropsychiatric diseases. The information available from the SRS itself may,
      therefore, reveal locations for autism susceptibility genes that would not
      otherwise be detected.

PMID- 20678251
TI  - Genome Integrity - a new open access journal.

PMID- 20678252
TI  - Localization of an hTERT repressor region on human chromosome 3p21.3 using
      chromosome engineering.
AB  - Telomerase is a ribonucleoprotein enzyme that synthesizes telomeric DNA. The
      reactivation of telomerase activity by aberrant upregulation/expression of its
      catalytic subunit hTERT is a major pathway in human tumorigenesis. However,
      regulatory mechanisms that control hTERT expression are largely unknown.
      Previously, we and others have demonstrated that the introduction of human
      chromosome 3, via microcell-mediated chromosome transfer (MMCT), repressed
      transcription of the hTERT gene. These results suggested that human chromosome 3
      contains a regulatory factor(s) involved in the repression of hTERT. To further
      localize this putative hTERT repressor(s), we have developed a unique
      experimental approach by introducing various truncated chromosome 3 regions
      produced by a novel chromosomal engineering technology into the renal cell
      carcinoma cell line (RCC23 cells). These cells autonomously express ectopic hTERT
      (exohTERT) promoted by a retroviral LTR promoter in order to permit cellular
      division after repression of endogenous hTERT. We found a telomerase repressor
      region located within a 7-Mb interval on chromosome 3p21.3. These results provide
      important information regarding hTERT regulation and a unique method to identify
      hTERT repressor elements.

PMID- 20678253
TI  - Inhibition of poly (ADP-Ribose) polymerase-1 in telomerase deficient mouse
      embryonic fibroblasts increases arsenite-induced genome instability.
AB  - BACKGROUND: The telomerase enzyme is a viable target for anti-cancer therapy
      given the innate differences in telomerase activity between tumour cells and
      normal somatic cells. However, the time lag between telomerase inhibition and
      telomeres becoming critically short to trigger cell death, allows cancer cells to
      acquire drug resistance. Inhibition of DNA repair pathways along with telomerase
      could be an alternative strategy to enhance anti-tumour effects and circumvent
      the possibility of drug resistance. Poly (ADP-Ribose) Polymerase-1 (PARP-1), an
      important DNA damage sensor and a DNA repair factor, has important roles in
      maintaining telomeres and chromosomal stability. In this study, the effects of
      combined inhibition of PARP-1 and telomerase in mouse embryonic fibroblasts
      (MEFs) following sodium arsenite exposure (a carcinogen and potent DNA damaging
      agent), were evaluated. RESULTS: Inhibition of PARP in telomerase deficient MEFs
      induced an increase in arsenite-induced DNA damage as compared to control cells.
      Combined inhibition also resulted in enhanced genomic instability, demonstrated
      by elevated micronuclei induction and chromosomal aberrations with decreased cell
      survival. In addition, telomerase inhibition in PARP-1 deficient MEFs led to
      greater telomere shortening and increased genomic instability. CONCLUSIONS: Our
      study demonstrated that the co-inhibition of PARP-1 and telomerase in MEFs
      rendered cells more susceptible to DNA damaging agents. Hence, these results
      offer support for the use of combined inhibition of PARP-1 and telomerase as a
      strategy to minimise the problems associated with long-term telomerase inhibition
      in cancer therapeutics.

PMID- 20678254
TI  - Defective Artemis causes mild telomere dysfunction.
AB  - BACKGROUND: Repair of DNA double strand breaks by non-homologous end joining
      (NHEJ) requires several proteins including Ku, DNA-PKcs, Artemis, XRCC4, Ligase
      IV and XLF. Two of these proteins, namely Ku and DNA-PKcs, are also involved in
      maintenance of telomeres, chromosome end-structures. In contrast, cells defective
      in Ligase IV and XRCC4 do not show changes in telomere length or function
      suggesting that these proteins are not involved in telomere maintenance. Since a
      mouse study indicated that defective Artemis may cause telomere dysfunction we
      investigated the effects of defective Artemis on telomere maintenance in human
      cells. RESULTS: We observed significantly elevated frequencies of telomeric
      fusions in two primary fibroblast cell lines established from Artemis defective
      patients relative to the control cell line. The frequencies of telomeric fusions
      increased after exposure of Artemis defective cells to ionizing radiation.
      Furthermore, we observed increased incidence of DNA damage at telomeres in
      Artemis defective cells that underwent more than 32 population doublings using
      the TIF (Telomere dysfunction Induced Foci) assay. We have also inhibited the
      expression levels of DNA-PKcs in Artemis defective cell lines by either using
      synthetic inhibitor (IC86621) or RNAi and observed their greater sensitivity to
      telomere dysfunction relative to control cells. CONCLUSION: These results suggest
      that defective Artemis causes a mild telomere dysfunction phenotype in human cell
      lines.

PMID- 20678255
TI  - Requirement of ATM-dependent pathway for the repair of a subset of DNA double
      strand breaks created by restriction endonucleases.
AB  - BACKGROUND: DNA double strand breaks induced by DNA damaging agents, such
      ionizing radiation, are repaired by multiple DNA repair pathways including non
      homologous end-joining (NHEJ) repair and homologous recombination (HR) repair.
      ATM-dependent DNA damage checkpoint regulates a part of DNA repair pathways,
      however, the exact role of ATM activity remains to be elucidated. In order to
      define the molecular structure of DNA double strand breaks requiring ATM activity
      we examined repair of DNA double strand breaks induced by different restriction
      endonucleases in normal human diploid cells treated with or without ATM-specific
      inhibitor. RESULTS: Synchronized G1 cells were treated with various restriction
      endonucleases. DNA double strand breaks were detected by the foci of
      phosphorylated ATM at serine 1981 and 53BP1. DNA damage was detectable 2 hours
      after the treatment, and the number of foci decreased thereafter. Repair of the
      3'-protruding ends created by Pst I and Sph I was efficient irrespective of ATM
      function, whereas the repair of a part of the blunt ends caused by Pvu II and Rsa
      I, and 5'-protruding ends created by Eco RI and Bam HI, respectively, were
      compromised by ATM inhibition. CONCLUSIONS: Our results indicate that ATM
      dependent pathway plays a pivotal role in the repair of a subset of DNA double
      strand breaks with specific end structures.

PMID- 20678256
TI  - Eukaryotic gene invasion by a bacterial mobile insertion sequence element IS2
      during cloning into a plasmid vector.
AB  - Escherichia coli (E. coli) are commonly used as hosts for DNA cloning and
      sequencing. Upon transformation of E. coli with recombined vector carrying a gene
      of interest, the bacteria multiply the gene of interest while maintaining the
      integrity of its content. During the subcloning of a mouse genomic fragment into
      a plasmid vector, we noticed that the size of the insert increased significantly
      upon replication in E. coli. The sequence of the insert was determined and found
      to contain a novel DNA sequence within the mouse genomic insert. A BLAST search
      of GenBank revealed the novel sequence to be that of the Insertion Sequence 2
      (IS2) element from E. coli that was likely inserted during replication in that
      organism. Importantly, a detailed search of GenBank shows that the IS2 is present
      within many eukaryotic nucleotide sequences, and in many cases, has been
      annotated as being part of the protein. The results of this study suggest that
      one must perform additional careful analysis of the sequence results using BLAST
      comparisons, and further verification of gene annotation before submission into
      the GenBank.

PMID- 20678257
TI  - UHRF1 is a genome caretaker that facilitates the DNA damage response to gamma
      irradiation.
AB  - BACKGROUND: DNA double-strand breaks (DSBs) caused by ionizing radiation or by
      the stalling of DNA replication forks are among the most deleterious forms of DNA
      damage. The ability of cells to recognize and repair DSBs requires post
      translational modifications to histones and other proteins that facilitate access
      to lesions in compacted chromatin, however our understanding of these processes
      remains incomplete. UHRF1 is an E3 ubiquitin ligase that has previously been
      linked to events that regulate chromatin remodeling and epigenetic maintenance.
      Previous studies have demonstrated that loss of UHRF1 increases the sensitivity
      of cells to DNA damage however the role of UHRF1 in this response is unclear.
      RESULTS: We demonstrate that UHRF1 plays a critical role for facilitating the
      response to DSB damage caused by gamma-irradiation. UHRF1-depleted cells exhibit
      increased sensitivity to gamma-irradiation, suggesting a compromised cellular
      response to DSBs. UHRF1-depleted cells show impaired cell cycle arrest and an
      impaired accumulation of histone H2AX phosphorylation (gammaH2AX) in response to
      gamma-irradiation compared to control cells. We also demonstrate that UHRF1 is
      required for genome integrity, in that UHRF1-depleted cells displayed an
      increased frequency of chromosomal aberrations compared to control cells.
      CONCLUSIONS: Our findings indicate a critical role for UHRF1 in maintenance of
      chromosome integrity and an optimal response to DSB damage.

PMID- 20678258
TI  - Radiation-induced DNA damage and repair in human gammadelta and alphabeta T
      lymphocytes analysed by the alkaline comet assay.
AB  - It has been shown by a number of authors that the radiosensitivity of peripheral
      blood mononuclear cells (PBMC) is higher in cancer patients compared to healthy
      donors, which is interpreted as a sign of genomic instability. PBMC are composed
      of different cell subpopulations which are differently radiosensitive and the
      difference between cancer patients and healthy donors could also be due to
      different composition of their PBMC pools. Gamma-delta T-lymphocytes play an
      important role in immunosurveillance and are promising cells for immunotherapy.
      Their abundance is frequently reduced in cancer patients so should their
      sensitivity to radiation be lower than that of other T-lymphocytes, this could,
      at least partly explain the low radiosensitivity of PBMC from healthy individuals
      compared to cancer patients. The present investigation was carried out to test
      this. Using the alkaline comet assay we analysed the level of DNA damage and
      repair in isolated gammadelta T-lymphocytes, pan T-lymphocytes and in total PBMC
      exposed in vitro to gamma radiation. We found no difference in the level of DNA
      damage and the capacity of DNA repair between the T cell populations. This is the
      first study that addresses the question of sensitivity to radiation of gamma
      delta T-cells.

PMID- 20678259
TI  - Candidate gene study of HOXB1 in autism spectrum disorder.
AB  - BACKGROUND: HOXB1 plays a major role in brainstem morphogenesis and could partly
      determine the cranial circumference in conjunction with HOXA1. In our sample,
      HOXA1 alleles significantly influence head growth rates both in autistic patients
      and in population controls. An initial report, suggesting that HOXB1 could confer
      autism vulnerability in interaction with HOXA1, was not confirmed by five small
      association studies. METHODS: Our sample includes 269 autistic individuals,
      belonging to 219 simplex and 28 multiplex families. A mutational analysis of the
      two exons and flanking intronic sequences of the HOXB1 gene was carried out in 84
      autistic patients by denaturing high performance liquid chromatography, followed
      by DNA sequencing. Identified rare variants were then searched by a restriction
      analysis in 236 autistic patients and 325-345 controls. Case-control and family
      based association studies were performed on two common variants in 169 Italian
      patients versus 184 Italian controls and in 247 trios. RESULTS: We identified
      three common polymorphisms, rs72338773 [c.82insACAGCGCCC (INS/nINS)], rs12939811
      [c.309A>T (Q103H)], and rs7207109 [c.450G>A (A150A)] and three rare variants,
      namely IVS1+63G>A, rs35115415 [c.702G>A (V234V)] and c.872_873delinsAA (S291N).
      SNPs rs72338773 and rs12939811 were not associated with autism, using either a
      case-control (alleles, exact P = 0.13) or a family-based design
      [transmission/disequilibrium test (TDT)chi2 = 1.774, P = 0.183]. The rare
      variants, all inherited from one of the parents, were present in two Italian and
      in two Caucasian-American families. Autistic probands in two families
      surprisingly inherited a distinct rare variant from each parent. The IVS1+63A
      allele was present in 3/690 control chromosomes, whereas rare alleles at
      rs35115415 and c.872_873delinsAA (S291N) were not found in 662 and 650 control
      chromosomes, respectively. The INS-T309 allele influenced head size, but its
      effect appears more modest and shows no interaction with HOXA1 alleles. The INS
      T309 allele is also associated with more severe stereotypic behaviours, according
      to ADI-R scores (N = 60 patients, P < 0.01). CONCLUSIONS: HOXB1 mutations do not
      represent a common cause of autism, nor do HOXB1 common variants play important
      roles in autism vulnerability. HOXB1 provides minor, albeit detectable
      contributions to head circumference in autistic patients, with HOXA1 displaying
      more prominent effects. HOXB1 variants may modulate the clinical phenotype,
      especially in the area of stereotypic behaviours.

PMID- 20678260
TI  - Defining the broader, medium and narrow autism phenotype among parents using the
      Autism Spectrum Quotient (AQ).
AB  - BACKGROUND: The Autism Spectrum Quotient (AQ) is a self-report questionnaire for
      quantifying autistic traits. This study tests whether the AQ can differentiate
      between parents of children with an autism spectrum condition (ASC) and control
      parents. In this paper, the use of the AQ to define the broader, medium and
      narrow autism phenotypes (BAP, MAP, NAP) is reported, and the proportion of
      parents with each phenotype is compared between the two groups. METHODS: A sample
      of 571 fathers and 1429 mothers of children with an ASC completed the AQ, along
      with 349 fathers and 658 mothers of developing typically children. RESULTS: Both
      mothers and fathers of the diagnosed children scored higher than the control
      parents on total AQ score and on four out of five of the subscales. Additionally,
      there were more parents of diagnosed children with a BAP, MAP or NAP.
      CONCLUSIONS: The AQ provides an efficient method for quantifying where an
      individual lies along the dimension of autistic traits, and extends the notion of
      a broader phenotype among first-degree relatives of those with ASC. The AQ is
      likely to have many applications, including population and clinical screening,
      and stratification in genetic studies.

PMID- 20678262
TI  - Abstracts of the Scandinavian Update on Trauma, Resuscitation and Emergency
      Medicine 2009. Stavanger, Norway. April 23-25, 2009.

PMID- 20678261
TI  - Low levels of ATM in breast cancer patients with clinical radiosensitivity.
AB  - BACKGROUND AND PURPOSE: Adjuvant radiotherapy for cancer can result in severe
      adverse side effects for normal tissues. In this respect, individuals with
      anomalies of the ATM (ataxia telangiectasia) protein/gene are of particular
      interest as they may be at risk of both breast cancer and clinical
      radiosensitivity. The association of specific ATM gene mutations with these
      pathologies has been well documented, however, there is uncertainty regarding
      pathological thresholds for the ATM protein. RESULTS: Semi-quantitative immuno
      blotting provided a reliable and reproducible method to compare levels of the ATM
      protein for a rare cohort of 20 cancer patients selected on the basis of their
      severe adverse normal tissue reactions to radiotherapy. We found that 4/12 (33%)
      of the breast cancer patients with severe adverse normal tissue reactions
      following radiotherapy had ATM protein levels < 55% compared to the mean for non
      reactor controls. CONCLUSIONS: ATM mutations are generally considered low risk
      alleles for breast cancer and clinical radiosensitivity. From results reported
      here we propose a tentative ATM protein threshold of ~55% for high-risk of
      clinical radiosensitivity for breast cancer patients.

PMID- 20678293
TI  - The marine limpet Notoacmea scapha acts as a transmission sink for intertidal
      cercariae in Otago Harbour, New Zealand.
AB  - Marine limpets, Notoacmea scapha, were collected from an intertidal mud flat in
      Otago Harbour, New Zealand, and examined for infection with larval trematodes.
      Three separate species of trematode (opecoelid sp. A, Acanthoparyphium sp. A and
      Curtuteria australis) were identified from the limpets, based on molecular
      evidence. This is the first report of these three trematodes in limpets,
      indicating that the latter are physiologically suitable second-intermediate
      hosts. However, based on ecological information on the diet of the parasites'
      definitive hosts, we conclude that the limpet N. scapha does not contribute to
      the transmission of any of the trematodes. Instead, it acts as a sink for
      cercariae that fail to locate appropriate second-intermediate hosts. 

PMID- 20678294
TI  - Drugs and nutrition: how side effects can influence nutritional intake.
AB  - There are many factors that can influence nutritional intake. Food availability,
      physical capability, appetite, presence of gastrointestinal symptoms and
      perception of food are examples. Drug therapy can negatively influence
      nutritional intake through their effect on these factors, predominantly due to
      side effects. This review aims to give a brief overview of each of these factors
      and how drug therapy can affect them. Specific examples are given for each
      section and an indication of the impact on nutritional status. This article aims
      to assist the clinician in the identification of the effects of drug therapy on
      nutritional intake and provides advice on appropriate intervention. A drug
      history and side effect review should form an integral part of nutritional
      assessment. Early identification and effective therapeutic use of alternative
      drug therapy can also positively influence nutritional intake.

PMID- 20678295
TI  - First fossil record of parasitism in Devonian calcareous sponges
      (stromatoporoids).
AB  - INTRODUCTION: Palaeozoic calcareous sponges (stromatoporoids) are common bio
      constructing fossils; they are sometimes found in association with helicoidal
      structures of unknown biological affinities. The interaction between the tube
      forming organisms has usually been classified as commensalism. METHODS: About 260
      stromatoporoid skeletons from the Middle Devonian (Givetian) of the Mont d'Haurs
      section near Givet (Champagne-Ardenne, France) were thin-sectioned and analysed
      under transmitted light. RESULTS: Approximately 10% of the examined
      stromatoporoids (mainly belonging to the genera Actinostroma, Stromatopora and
      Stromatoporella) contain tubes classified as Torquaysalpinx sp. The
      Torquaysalpinx organisms penetrated the skeletons of stromatoporoids in vivo (as
      evidenced by skeletal overgrowths); around the infesting organisms, growth bands
      are bent down. CONCLUSION: Diminished growth rates around the infesting organism
      demonstrate a negative influence on the host, similar to that seen in the modern
      demosponge-polychaete association of Verongia-Haplosyllis. This is demonstrated
      by changes in growth bands. As in the above-mentioned association, the
      endosymbiont might have been feeding directly upon the tissues of the host. The
      Torquaysalpinx organisms were gaining habitat and possibly also food resources -
      for them this interaction was clearly positive. This long-term association can
      therefore be classified as parasitism. This is the first evidence for parasitism
      in Palaeozoic sponges.

PMID- 20678296
TI  - Comparison of gene expression patterns among Leishmania braziliensis clinical
      isolates showing a different in vitro susceptibility to pentavalent antimony.
AB  - INTRODUCTION: Evaluation of Leishmania drug susceptibility depends on in vitro
      Sb(V) susceptibility assays, which are labour-intensive and may give a biased
      view of the true parasite resistance. Molecular markers are urgently needed to
      improve and simplify the monitoring of Sb(V)-resistance. We analysed here the
      gene expression profile of 21 L. braziliensis clinical isolates in vitro defined
      as Sb(V)-resistant and -sensitive, in order to identify potential resistance
      markers. METHODS: The differential expression of 13 genes involved in Sb(V)
      metabolism, oxidative stress or housekeeping functions was analysed during in
      vitro promastigote growth. RESULTS: Expression profiles were up-regulated for 5
      genes only, each time affecting a different set of isolates (mosaic picture of
      gene expression). Two genes, ODC (ornithine decarboxylase) and TRYR
      (trypanothione reductase), showed a significantly higher expression rate in the
      group of Sb(V)-resistant compared to the group of Sb(V)-sensitive parasites
      (P<0.01). However, analysis of individual isolates showed both markers to explain
      only partially the drug resistance. DISCUSSION: Our results might be explained by
      (i) the occurrence of a pleiotropic molecular mechanism leading to the in vitro
      Sb(V) resistance and/or (ii) the existence of different epi-phenotypes not
      revealed by the in vitro Sb(V) susceptibility assays, but interfering with the
      gene expression patterns.

PMID- 20678297
TI  - Contrasting patterns of deficits in visuospatial memory and executive function in
      patients with major depression with and without ECT referral.
AB  - BACKGROUND: The pretreatment neuropsychological profile of drug-resistant
      patients with major depressive disorder (MDD) referred for electroconvulsive
      therapy (ECT) may differ from that of their drug-respondent MDD counterparts.
      Such differences could help in identifying distinct MDD subtypes, thus offering
      insights into the neuropathology underlying differential treatment responses.
      METHOD: Depressed patients with ECT referral (ECTs), depressed patients with no
      ECT referral (NECTs) and non-psychiatric Controls (matched groups, n=15) were
      assessed with memory and executive function tests from the Cambridge
      Neuropsychological Test Automated Battery (CANTAB). RESULTS: ECTs scored
      significantly lower than NECTs in the Mini-Mental State Examination (MMSE;
      p=0.01). NECTs performed worse than Controls in the Paired Associates Learning
      (PAL) task (p<0.03; Control/NECT p<0.01) and the Spatial Recognition Memory (SRM)
      task (p<0.05; Controls/NECTs p<0.05); ECTs performed between Controls and NECTs,
      not differing from either. In the Intra/Extradimensional (IED) set-shifting task,
      ECTs performed worse that Controls and NECTS (IED: p<0.01; Controls/ECTs p<0.01),
      particularly in the shift phases, which suggests reduced attentional flexibility.
      In Stockings of Cambridge (SOC), ECTs abandoned the test early more often than
      Controls and NECTs (H=11, p<0.01) but ECTs who completed SOC performed comparably
      to the other two groups. CONCLUSIONS: A double dissociation emerged from the
      comparison of cognitive profiles of ECT and NECT patients. ECTs showed executive
      deficits, particularly in attentional flexibility, but mild deficits in tests of
      visuospatial memory. NECTs presented the opposite pattern. This suggests
      predominantly frontostriatal involvement in ECT versus temporal involvement in
      NECT depressives.

PMID- 20678298
TI  - A study of severe domestic squalor: 173 cases referred to an old age psychiatry
      service.
AB  - BACKGROUND: Although community psychiatric services commonly encounter cases
      where intervention is needed due to persons' unclean or cluttered living
      conditions, evidence concerning the referral rate and prevalence of severe
      domestic squalor is sparse. METHODS: Between 2000 and 2009, ratings of
      cleanliness and clutter have been made in all cases of people living in squalor
      who have been referred to an old age psychiatry service in Central Sydney. Where
      possible, one-year follow-up was arranged. RESULTS: 173 persons aged 65 years or
      more were referred to the service during the ten years and assessed as living in
      squalor (120 moderate or severe, two thirds of whom showed a moderate or severe
      degree of hoarding/clutter). Of 157 followed up after one year, 47% were still at
      home, 32% were in long-term care homes, 12% had moved elsewhere, and 9% had died.
      The annual new referral rate was close to 1 per 1000 elderly people in the
      catchment area, and of moderate or severe squalor was 0.66 per 1000. Limiting
      follow-up to those in moderate or severe squalor, 41% were still at home one year
      later. Current findings suggest that the minimum prevalence in the community of
      older people living in moderate or severe squalor in Sydney is 1 per 1000.
      CONCLUSIONS: The costs of intervening in cases of severe domestic squalor are
      considerable. Increased attention and funding are warranted, as the incidence and
      prevalence are higher than had previously been estimated.

PMID- 20678299
TI  - Course of neuropsychiatric symptoms in residents with dementia in long-term care
      institutions: a systematic review.
AB  - BACKGROUND: Neuropsychiatric symptoms (NPS) occur frequently in residents of long
      term care institutions. The aim of this study was to review the literature
      systematically on the course of NPS in residents with dementia in long-term care
      institutions. METHODS: A systematic literature search was conducted using
      Medline, PsychInfo, Embase and Cinahl. Search terms included "dementia", "long
      term care institutions", "NPS", "longitudinal", and additional related terms. All
      titles and abstracts were independently assessed for inclusion and for
      methodological quality by two researchers, and the full texts of relevant papers
      were retrieved. Inclusion criteria were: dementia diagnosis, long-term care
      institutions, NPS, and longitudinal design. RESULTS: The literature search
      revealed 1982 papers of which 18 met the inclusion criteria. The patients were
      predominately female and aged 75 years and over. The follow-up period ranged from
      three months to one year. The number of assessments ranged from two to five, and
      12 different assessment instruments were used to study NPS. Aberrant motor
      behavior, depression, anxiety, and euphoria showed decline over time, and
      psychosis remained constant whereas apathy, agitation, irritability, and
      disinhibition increased over time. All symptoms showed specific intermittent
      courses. The methodological quality of the literature was limited by the small
      sample sizes, short follow-up periods, and lack of comprehensive neuropsychiatric
      assessment instruments. CONCLUSIONS: In the reviewed studies, NPS in
      institutionalized residents with dementia showed a heterogeneous course, although
      methodological limitations and the diversity of the studies call for caution in
      interpretation. Future research should focus on large prospective cohort studies
      with institutionalized residents with dementia, examining a wide range of NPS.

PMID- 20678300
TI  - Can the CAMCOG be a good cognitive test for patients with Alzheimer's disease
      with low levels of education?
AB  - BACKGROUND: The Cambridge Cognitive Examination (CAMCOG) is a useful test in
      screening for Alzheimer's disease (AD). However, the interpretation of CAMCOG cut
      off scores is problematic and reference values are needed for different
      educational strata. Given the importance of earlier diagnoses of mild dementia,
      new cut-off values are required which take into account patients with low levels
      of education. This study aims to evaluate whether the CAMCOG can be used as an
      accurate screening test among AD patients and normal controls with different
      educational levels. METHODS: Cross-sectional assessment was undertaken of 113 AD
      and 208 elderly controls with heterogeneous educational levels (group 1: 1-4
      years; group 2: 5-8 years; and group 3: >= 9 years) from a geriatric clinic.
      submitted to a thorough diagnostic evaluation for AD including the Cambridge
      Examination for Mental Disorders of the Elderly (CAMDEX). Controls had no
      cognitive or mood complaints. Sensitivity (SE) and specificity (SP) for the
      CAMCOG in each educational group was assessed with receiver-operator
      characteristic (ROC) curves. RESULTS: CAMCOG mean values were lower when
      education was reduced in both diagnostic groups (controls - group 1: 87; group 2:
      91; group 3: 96; AD - group 1: 63; group 2: 62; group 3: 77). Cut-off scores for
      the three education groups were 79, 80 and 90, respectively. SE and SP varied
      among the groups (group 1: 88.1% and 83.5%; group 2: 84.6% and 96%; group 3:
      70.8% and 90%). CONCLUSION: The CAMCOG can be used as a cognitive test for
      patients with low educational level with good accuracy. Patients with higher
      education showed lower scores than previously reported.

PMID- 20678301
TI  - The role of literacy, occupation and income in dementia prevention: the Sao Paulo
      Ageing & Health Study (SPAH).
AB  - BACKGROUND: Dementia is now a major public health issue in low- and middle-income
      countries, and strategies for primary prevention are needed. This study aimed to
      estimate the proportion of cases of dementia attributable to illiteracy, non
      skilled occupation and low income, which are common, potentially modifiable
      social adversities that occur along the lifespan in low- and middle-income
      countries. METHODS: This report is based on data from the Sao Paulo Ageing &
      Health Study (SPAH) study (N = 2003). All individuals aged 65 years and older
      residing within pre-defined socially deprived areas of the city of Sao Paulo,
      Brazil, were included. The outcome of interest was prevalent dementia. Indicators
      of socioeconomic position (SEP) were literacy (distal indicator), highest
      occupational attainment (intermediate indicator), and monthly personal income
      (proximal indicator). We estimated the proportion of prevalent dementia
      attributable to each SEP indicator (illiteracy, non-skilled occupations and low
      income) by calculating their population attributable fractions (PAF). RESULTS:
      Dementia was more prevalent amongst participants who were illiterate, had non
      skilled occupations and lower income. Illiteracy, poor occupational achievement
      and low income accounted for 22.0%, 38.5% and 38.5% of the cases of dementia,
      respectively. There was a cumulative effect of socioeconomic adversities during
      the lifespan, and nearly 50% of the prevalence of dementia could be potentially
      attributed to the combination of two or three of the socioeconomic adversities
      investigated. CONCLUSIONS: Public policies aimed at improving education,
      occupational skills and income could potentially have a role in primary
      prevention of dementia. Governments should address this issue in a purposeful and
      systematic way.

PMID- 20678302
TI  - Neuropsychiatric symptoms and syndromes in institutionalized elderly people
      without dementia.
AB  - BACKGROUND: Neuropsychiatric disorders are mainly studied in people with dementia
      but estimates are still not available for institutionalized elderly people
      without dementia. The aim of this work was to investigate neuropsychiatric
      syndromes in non-demented elderly people living in residential facilities (RFs).
      METHODS: Data from the PROGRES-Older people project, including 95 RFs in Italy,
      were analyzed. From a total of 1215 people, 252 without dementia were recruited.
      Behavioral syndromes were identified using both factor and cluster analysis of
      results from the 12-item Neuropsychiatric Inventory. Logistic regression was used
      to assess factors associated with behavioral syndromes. Global cognitive
      functioning was assessed with the Mini-mental State Examination (MMSE). Current
      pharmacological treatments were taken from the residents' records. RESULTS: Five
      neuropsychiatric syndromes were identified: (1) Affective (depression, anxiety,
      night-time behaviors); (2) Hyperactive (agitation, irritability, appetite
      abnormalities); (3) Psychotic (delusions and hallucinations); (4) Manic (euphoria
      and disinhibition); (5) Apathetic (apathy and aberrant motor behavior). The risk
      of having a neuropsychiatric syndrome was higher in people with younger age (OR:
      5.1, 1.3-20.0), higher education (OR: 7.3, 2.4-22.1), and low MMSE score (OR:
      6.5, 1.9-22.2). Almost half of people with behavioral syndromes were not
      undergoing psychotropic treatment. Hypnotic and anxiolytic agents were the most
      frequently used drugs for most of the syndromes. CONCLUSIONS: Older people
      without dementia living in RFs exhibit a syndrome pattern of neuropsychiatric
      behaviors different from those observed in patients with dementia, which are
      associated with cognitive and sociodemographic characteristics. A large
      proportion of non-demented older people with neuropsychiatric syndromes are not
      having adequate treatment for their psychiatric disturbances.

PMID- 20678303
TI  - Depression in nursing homes.
AB  - BACKGROUND: Although studies have shown the prevalence of depression in nursing
      homes to be high, under-recognition of depression in these facilities is
      widespread. Use of screening tests to enhance detection of depressive symptoms
      has been recommended. METHODS: This paper aims to provoke discussion about
      optimal management of depression in nursing homes. The utility of the Cornell
      Scale for Depression in Dementia (CSDD) is considered. CSDD data relating to
      residents assessed in 2008-2009 were collected from three Sydney nursing homes.
      RESULTS: CSDD scores were available from 162 residents, though raters stated they
      were unable to score participants on at least one item in 47 cases. Scores of 13
      or more were recorded for 23% of residents in these facilities, but in most of
      these cases little was documented in case files to show that the results had been
      discussed by staff, or that they led to interventions, or that follow-up testing
      was arranged. CONCLUSIONS: Results of CSDD testing should prompt care staff
      (including doctors) to consider causation of depression in cases where residents
      are identified as possibly depressed. In particular, there needs to be discussion
      of how to help residents to cope with disability, losses, and feelings of
      powerlessness. Research is needed, examining factors that might predict response
      to antidepressants, and what else helps. Accreditation of nursing homes could be
      made to depend partly on evidence that staff regularly search for, and (if found)
      ensure appropriate responses to, depression.

PMID- 20678304
TI  - Chronic pubertal cannabinoid treatment as a behavioural model for aspects of
      schizophrenia: effects of the atypical antipsychotic quetiapine.
AB  - Chronic pubertal cannabinoid treatment in rats has been suggested for modelling
      aspects of schizophrenia since it results in long-lasting behavioural alterations
      reflecting certain characteristics of schizophrenia symptomatology. Lasting
      deficits in sensorimotor gating, impaired short-term mnemonic processing, reduced
      motivation as well as inappropriate and deficient social behaviour have been
      reported after chronic cannabinod treatment during pubertal development. In
      addition, sensorimotor gating deficits were able to be restored by acute
      injections of the typical antipsychotic haloperidol. The aim of this study was to
      examine possible acute as well as lasting beneficial effects of the atypical
      antipsychotic drug quetiapine in adult animals undergoing chronic treatment of
      the synthetic cannabinoid receptor agonist WIN 55,212-2 (WIN) (1.2 mg/kg) during
      puberty. Therefore, animals were tested repeatedly for their performance in
      social interaction and social recognition after acute and chronic quetiapine
      treatment. Chronic pubertal WIN treatment induced persistent deficits in social
      recognition and impaired social interaction. Acute quetiapine treatment was able
      to completely restore those deficits in social behaviour and social memory.
      Social recognition memory was affected again 1 wk after cessation of chronic
      quetapine treatment; however, in social interaction persistent improvements could
      be detected. In conclusion, the results indicate that the atypical antipsychotic
      drug quetiapine is able to acutely restore deficits in social behaviour induced
      by developmental cannabinoid exposure and even exert some persistent beneficial
      effects. Furthermore, the present data give further support and validity for the
      suitability of chronic pubertal cannabinoid administration as an animal model for
      aspects of schizophrenia.

PMID- 20678305
TI  - Characterization of electroconvulsive seizure-induced TIMP-1 and MMP-9 in
      hippocampal vasculature.
AB  - Degradation of the vascular basement membrane stimulates angiogenesis and is
      tightly controlled by balancing the actions of metalloproteases and their
      inhibitors. Previous work demonstrated that electroconvulsive seizure (ECS)
      elevates angiogenic factors and endothelial proliferation in the hippocampus. The
      robust induction of tissue inhibitor of matrix metalloprotease 1 (TIMP-1) in the
      stratum lacunosum moleculare (SLM) corresponds to sites of increased vascular
      density. This led us to examine the spatial and cellular expression of TIMP-1 and
      its substrate, matrix metalloprotease 9 (MMP-9). Chronic ECS increased TIMP-1 by
      12-fold and MMP-9 by 3-fold in discrete SLM cells. We then characterized the
      expression of TIMP-1 mRNA in relation to vasculature in the SLM and glial
      limiting membrane (GLM). Employing laser microdissection we identified the cell
      types associated with SLM vasculature and also phenotyped the cells expressing
      TIMP-1 and MMP-9. We concluded that TIMP-1 is produced by perivascular cells
      positive for alpha smooth actin and that MMP-9 is expressed by GFAP-positive
      astrocytes. These studies suggest that ECS-induced remodelling occurs at the
      vascular basement membrane and facilitates neovascularization.

PMID- 20678307
TI  - Variability in practice patterns of shared-specific versus patient-specific
      immunotherapy by practicing allergists and allergy program directors and
      implications for practice parameters.

PMID- 20678306
TI  - Twenty-six-week efficacy and safety study of mometasone furoate/formoterol 200/10
      microg combination treatment in patients with persistent asthma previously
      receiving medium-dose inhaled corticosteroids.
AB  - Asthma is a heterogeneous condition characterized by reduced lung function,
      chronic inflammation, and periodic asthma deteriorations. This study was
      performed to evaluate the effect of mometasone furoate (MF)/formoterol (F)
      combination, 200/10 microg, administered twice daily (b.i.d.) on asthma
      deteriorations and pulmonary function in patients with asthma uncontrolled on
      medium-dose inhaled corticosteroid (ICS). After 2- to 3-week open-label run-in
      with MF 200 microg b.i.d., patients (>or=12 years) were randomized to 26 weeks of
      treatment with MF/F 200/10 microg, MF 200 microg, F 10 microg, or placebo b.i.d.
      Coprimary end points were time to first asthma deterioration (MF/F versus F) and
      bronchodilation, assessed by the area under the curve of the change in forced
      expiratory volume in 1 second 0-12 hours (FEV(1) AUC(0-12h); MF/F versus MF). A
      total of 781 patients were randomized. Treatment with MF/F 200/10 microg reduced
      asthma deteriorations and clinically judged deteriorations (i.e., deterioration
      resulting in emergency treatment, hospitalization, or treatment with additional
      excluded asthma medication [i.e., systemic corticosteroids]). The proportion of
      patients experiencing asthma deteriorations was MF/F, 30.4%; MF, 33.9%; F, 54.0%;
      placebo, 55.6% (p < 0.001, MF/F versus F and placebo). There was a sixfold
      reduction in clinically judged deteriorations with MF/F versus F and placebo (p <
      0.001). Lung function improved more rapidly with MF/F than MF and placebo. Mean
      change from baseline FEV(1) AUC(0-12h) at week 12 was MF/F, 11.7% versus MF,
      5.7%; F, 8.5%; and placebo, 3.9% (p < 0.001). Treatment-related AEs were rare and
      similar across groups. Treatment with MF/F 200/10 microg was effective in
      reducing the risk of asthma deteriorations. MF/F was safe and provided rapid and
      sustained bronchodilation in patients with asthma.

PMID- 20678308
TI  - An innovative and cost-effective way of managing ankle fractures prior to surgery
      -home therapy.
AB  - INTRODUCTION: Ankle fractures are common injuries affecting all age groups and
      constitute a large proportion of the orthopaedic trauma case load. Patients are
      usually admitted directly to the ward from the emergency department and a large
      number of bed-days are spent waiting for the ankle swelling to subside prior to
      surgery. We audited current practice and then implemented a home therapy
      programme (HTP). The purpose of the study was to assess the pioneering HTP with
      respect to cost effectiveness, length of stay and patient satisfaction. PATIENTS
      AND METHODS: If HTP criteria were met, patients with reduced, unstable ankle
      fractures were taught safe mobilisation by physiotherapists in the emergency
      department. They were then discharged home to ice and elevate their ankle in a
      plaster backslab. A provisional operation date was allocated on discharge. They
      were admitted to hospital the day of surgery and then discharged home when safe
      and comfortable. RESULTS: Forty-three consecutive patients met our inclusion
      criteria and underwent surgical fixation of unstable ankle fractures over a 3
      month period (February-April 2008). The average length of hospital stay was 8
      days (range, 1-18 days), 4.5 days pre-operatively and 3.5 days postoperatively.
      Patients were frustrated and dissatisfied with the whole process. In total, 177
      patients underwent surgical fixation of unstable ankle fractures over an 11-month
      period (November 2008 to October 2009) and, of these, 59 met the home therapy
      criteria. The average length of hospital stay was 2.4 days, 1 day pre-operatively
      (range, 0-4 days) and 1.4 days postoperatively (range, 0-5 days). All HTP
      patients expressed satisfaction with the process. Over the course of the HTP, 354
      bed-days were saved which equates to a saving of L81,774. The annual estimated
      cost saving is L90,000. CONCLUSIONS: The home therapy programme has proved
      effective in reducing hospital stay both pre- and postoperatively. It is cost
      effective and well received by patients.

PMID- 20678309
TI  - Bilateral type 1 capitellar fractures: a case report.
AB  - There have been no cases of bilateral type I capitellar fractures reported in the
      UK, and only two reported world-wide. This report describes the clinical case of
      a 26-year-old woman, who fell sustaining this injury, and how careful management
      resulted in an excellent outcome. This case highlights the rarity of this injury,
      its potential morbidity, and an approach to its management which produces
      excellent clinical results.

PMID- 20678310
TI  - One health approach to influenza: assessment of critical issues and options.
AB  - A task force of experts on influenza, public health, and animal health met at the
      conference One Health Approach to Influenza: Assessment of Critical Issues and
      Options in Washington, DC, on December 1-2, 2009. These experts discussed the
      role of the One Health approach in preparing for and responding to an influenza
      pandemic or other emerging zoonotic disease by using pandemic (H1N1) 2009 as a
      case study. The meeting was convened by the US Department of Homeland Security
      National Center for Foreign Animal and Zoonotic Disease Defense, and the National
      Institute of Allergy and Infectious Diseases/National Institutes of Health
      Western Regional Center of Excellence for Biodefense and Emerging Infectious
      Diseases.

PMID- 20678311
TI  - Hantavirus infections in humans and animals, China.
AB  - Hemorrhagic fever with renal syndrome (HFRS) is a serious public health problem
      in the People's Republic of China. Although 7 sero/genotypes of hantaviruses have
      been found in rodents, only Hantaan virus (carried by Apodemus agrarius mice) and
      Seoul virus (carried by Rattus norvegicus rats) reportedly cause disease in
      humans. During 1950-2007, a total of 1,557,622 cases of HFRS in humans and 46,427
      deaths (3%) were reported in China. HFRS has been reported in 29 of 31 provinces
      in China. After implementation of comprehensive preventive measures, including
      vaccination, in the past decade in China, incidence of HFRS has dramatically
      decreased; only 11,248 HFRS cases were reported in 2007. Mortality rates also
      declined from the highest level of 14.2% in 1969 to ?1% during 1995-2007.
      However, the numbers of HFRS cases and deaths in China remain the highest in the
      world.

PMID- 20678312
TI  - Clostridium difficile bacteremia, Taiwan.
AB  - To determine clinical characteristics and outcome of patients with Clostridium
      difficile bacteremia (CDB), we identified 12 patients with CDB in 2 medical
      centers in Taiwan; all had underlying systemic diseases. Five had
      gastrointestinal diseases or conditions, including pseudomembranous colitis (2
      patients); 4 recalled diarrhea, but only 5 had recent exposure to antimicrobial
      drugs. Ten available isolates were susceptible to metronidazole and vancomycin.
      Five isolates had C. difficile toxin A or B. Of 5 patients who died, 3 died of
      CDB. Of 8 patients treated with metronidazole or vancomycin, only 1 died, and all
      4 patients treated with other drugs died (12.5% vs. 100%; p = 0.01). C. difficile
      bacteremia, although uncommon, is thus associated with substaintial illness and
      death rates.

PMID- 20678313
TI  - Responses to pandemic (H1N1) 2009, Australia.
AB  - In 2007, adults in Australia were interviewed about their willingness to comply
      with potential health interventions during a hypothetical influenza outbreak.
      After the first wave of pandemic (H1N1) 2009 in Australia, many of the same
      respondents were interviewed about behavior and protection measures they actually
      adopted. Of the original 1,155 respondents, follow-up interviews were conducted
      for 830 (71.9%). Overall, 20.4% of respondents in 2009 had recently experienced
      influenza-like illness, 77.7% perceived pandemic (H1N1) 2009 to be mild, and
      77.8% reported low anxiety. Only 14.5% could correctly answer 4 questions about
      influenza virus transmission, symptoms, and infection control. Some reported
      increasing handwashing (46.6%) and covering coughs and sneezes (27.8%) to reduce
      transmission. Compared with intentions reported in 2007, stated compliance with
      quarantine or isolation measures in 2009 remained high. However, only respondents
      who perceived pandemic (H1N1) 2009 as serious or who had attained higher
      educational levels expressed intention to comply with social distancing measures.

PMID- 20678314
TI  - Bat coronaviruses and experimental infection of bats, the Philippines.
AB  - Fifty-two bats captured during July 2008 in the Philippines were tested by
      reverse transcription-PCR to detect bat coronavirus (CoV) RNA. The overall
      prevalence of virus RNA was 55.8%. We found 2 groups of sequences that belonged
      to group 1 (genus Alphacoronavirus) and group 2 (genus Betacoronavirus) CoVs.
      Phylogenetic analysis of the RNA-dependent RNA polymerase gene showed that groups
      1 and 2 CoVs were similar to Bat-CoV/China/A515/2005 (95% nt sequence identity)
      and Bat-CoV/HKU9-1/China/2007 (83% identity), respectively. To propagate group 2
      CoVs obtained from a lesser dog-faced fruit bat (Cynopterus brachyotis), we
      administered intestine samples orally to Leschenault rousette bats (Rousettus
      leschenaulti) maintained in our laboratory. After virus replication in the bats
      was confirmed, an additional passage of the virus was made in Leschenault
      rousette bats, and bat pathogenesis was investigated. Fruit bats infected with
      virus did not show clinical signs of infection.

PMID- 20678315
TI  - Multiyear surveillance for avian influenza virus in waterfowl from wintering
      grounds, Texas coast, USA.
AB  - We studied the prevalence of influenza A virus in wintering waterfowl from the
      Central Flyway on the Gulf Coast of Texas. Of 5,363 hunter-harvested migratory
      and resident waterfowl and wetland-associated game birds sampled during 3
      consecutive hunting seasons (September-January 2006-07, 2007-08, and 2008-09),
      real-time reverse transcription-PCR detected influenza A matrix sequences in 8.5%
      of samples, H5 in 0.7%, and H7 in 0.6%. Virus isolation yielded 134 influenza A
      viruses, including N1-N9, H1-H7, H10, and H11 subtypes. Low-pathogenicity H7
      subtype was isolated during January, September, and November 2007 and January
      2008; low-pathogenicity H5 subtype was isolated during November and December
      2007.

PMID- 20678316
TI  - Outbreak of Corynebacterium pseudodiphtheriticum infection in cystic fibrosis
      patients, France.
AB  - An increasing body of evidence indicates that nondiphtheria corynebacteria may be
      responsible for respiratory tract infections. We report an outbreak of
      Corynebacterium pseudodiphtheriticum infection in children with cystic fibrosis
      (CF). To identify 18 C. pseudodiphtheriticum strains isolated from 13 French
      children with CF, we used molecular methods (partial rpoB gene sequencing) and
      matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass
      spectrometry. Clinical symptoms were exhibited by 10 children (76.9%), including
      cough, rhinitis, and lung exacerbations. The results of MALDI-TOF identification
      matched perfectly with those obtained from molecular identification.
      Retrospective analysis of sputum specimens by using specific real-time PCR showed
      that approximately 20% of children with CF were colonized with these bacteria,
      whereas children who did not have CF had negative test results. Our study
      reemphasizes the conclusion that correctly identifying bacteria at the species
      level facilitates detection of an outbreak of new or emerging infections in
      humans.

PMID- 20678317
TI  - White-nose syndrome fungus (Geomyces destructans) in bats, Europe.
AB  - White-nose syndrome is an emerging disease in North America that has caused
      substantial declines in hibernating bats. A recently identified fungus (Geomyces
      destructans) causes skin lesions that are characteristic of this disease. Typical
      signs of this infection were not observed in bats in North America before white
      nose syndrome was detected. However, unconfirmed reports from Europe indicated
      white fungal growth on hibernating bats without associated deaths. To investigate
      these differences, hibernating bats were sampled in Germany, Switzerland, and
      Hungary to determine whether G. destructans is present in Europe. Microscopic
      observations, fungal culture, and genetic analyses of 43 samples from 23 bats
      indicated that 21 bats of 5 species in 3 countries were colonized by G.
      destructans. We hypothesize that G. destructans is present throughout Europe and
      that bats in Europe may be more immunologically or behaviorally resistant to G.
      destructans than their congeners in North America because they potentially
      coevolved with the fungus.

PMID- 20678318
TI  - Scavenging ducks and transmission of highly pathogenic avian influenza, Java,
      Indonesia.
AB  - In Java, Indonesia, during March 2007-March 2008, 96 farms with scavenging ducks
      that were not vaccinated against highly pathogenic avian influenza (HPAI) were
      monitored bimonthly. Bird-level (prevalence among individual birds) H5
      seroprevalence was 2.6% for ducks and 0.5% for chickens in contact with ducks. At
      least 1 seropositive bird was detected during 19.5% and 2.0% of duck- and chicken
      flock visits, respectively. Duck flocks were 12.4x more likely than chicken
      flocks to have seropositive birds. During 21.4% of farm visits, <or=1 sampled
      duck was H5 seropositive when all sampled in-contact chickens were seronegative.
      Subtype H5 virus was detected during 2.5% of duck-flock visits and 1.5% of
      chicken-flock visits. When deaths from HPAI infection occurred, H5 virus shedding
      occurred in apparently healthy birds on 68.8% of farms. Of 180 poultry deaths
      investigated, 43.9% were attributed to H5 virus. These longitudinal study results
      indicate that ducks are a source of infection for chickens and, potentially, for
      humans.

PMID- 20678319
TI  - West Nile virus range expansion into British Columbia.
AB  - In 2009, an expansion of West Nile virus (WNV) into the Canadian province of
      British Columbia was detected. Two locally acquired cases of infection in humans
      and 3 cases of infection in horses were detected by ELISA and plaque-reduction
      neutralization tests. Ten positive mosquito pools were detected by reverse
      transcription PCR. Most WNV activity in British Columbia in 2009 occurred in the
      hot and dry southern Okanagan Valley. Virus establishment and amplification in
      this region was likely facilitated by above average nightly temperatures and a
      rapid accumulation of degree-days in late summer. Estimated exposure dates for
      humans and initial detection of WNV-positive mosquitoes occurred concurrently
      with a late summer increase in Culex tarsalis mosquitoes (which spread western
      equine encephalitis) in the southern Okanagan Valley. The conditions present
      during this range expansion suggest that temperature and Cx. tarsalis mosquito
      abundance may be limiting factors for WNV transmission in this portion of the
      Pacific Northwest.

PMID- 20678320
TI  - Pandemic (H1N1) 2009 surveillance for severe illness and response, New York, New
      York, USA, April-July 2009.
AB  - On April 23, 2009, the New York City Department of Health and Mental Hygiene
      (DOHMH) was notified of a school outbreak of respiratory illness; 2 days later
      the infection was identified as pandemic (H1N1) 2009. This was the first major
      outbreak of the illness in the United States. To guide decisions on the public
      health response, the DOHMH used active hospital-based surveillance and then
      enhanced passive reporting to collect data on demographics, risk conditions, and
      clinical severity. This surveillance identified 996 hospitalized patients with
      confirmed or probable pandemic (H1N1) 2009 virus infection from April 24 to July
      7; fifty percent lived in high-poverty neighborhoods. Nearly half were <18 years
      of age. Surveillance data were critical in guiding the DOHMH response. The DOHMH
      experience during this outbreak illustrates the need for the capacity to rapidly
      expand and modify surveillance to adapt to changing conditions.

PMID- 20678322
TI  - Pearl Kendrick, Grace Eldering, and the pertussis vaccine.
AB  - In light of the reemergence of pertussis (whooping cough), the pioneering
      research of Pearl Kendrick and Grace Eldering is worth revisiting. In the 1930s,
      working in the Michigan Department of Health laboratory in Grand Rapids,
      Michigan, USA, they began researching a pertussis vaccine. Their research offers
      an instructive case study of the creative public health research performed in
      state health department laboratories during the interwar years. State department
      of health laboratory directors actively promoted research by supporting advanced
      education; making facilities and funding available for individual projects; and,
      when possible, procuring new facilities. Using Michigan Department of Health
      resources and local and federal funding, Kendrick and Eldering developed
      standardized diagnostic tools; modified and improved extant vaccines; conducted
      the first successful, large-scale, controlled clinical trial of pertussis
      vaccine; and participated in international efforts to standardize and disseminate
      the vaccine. Their model may again offer a promising avenue for groundbreaking
      research.

PMID- 20678321
TI  - Correlation of pandemic (H1N1) 2009 viral load with disease severity and
      prolonged viral shedding in children.
AB  - Pandemic (H1N1) 2009 virus causes severe illness, including pneumonia, which
      leads to hospitalization and even death. To characterize the kinetic changes in
      viral load and identify factors of influence, we analyzed variables that could
      potentially influence the viral shedding time in a hospital-based cohort of 1,052
      patients. Viral load was inversely correlated with number of days after the onset
      of fever and was maintained at a high level over the first 3 days. Patients with
      pneumonia had higher viral loads than those with bronchitis or upper respiratory
      tract infection. Median viral shedding time after the onset of symptoms was 9
      days. Patients <13 years of age had a longer median viral shedding time than
      those >or=13 years of age (11 days vs. 7 days). These results suggest that
      younger children may require a longer isolation period and that patients with
      pneumonia may require treatment that is more aggressive than standard therapy for
      pandemic (H1N1) 2009 virus.

PMID- 20678324
TI  - Duck hunters' perceptions of risk for avian influenza, Georgia, USA.
AB  - To determine duck hunters'risk for highly pathogenic avian influenza, we surveyed
      duck hunters in Georgia, USA, during 2007-2008, about their knowledge, attitudes,
      and practices. We found they engage in several practices that could expose them
      to the virus. Exposures and awareness were highest for those who had hunted >10
      years.

PMID- 20678325
TI  - Amblyomma imitator ticks as vectors of Rickettsia rickettsii, Mexico.
AB  - Real-time PCR of Amblyomma imitator tick egg masses obtained in Nuevo Leon State,
      Mexico, identified a Rickettsia species. Sequence analyses of 17-kD common
      antigen and outer membrane protein A and B gene fragments showed to it to be R.
      rickettsii, which suggested a potential new vector for this bacterium.

PMID- 20678326
TI  - Bat rabies in Massachusetts, USA, 1985-2009.
AB  - To investigate rabies in Massachusetts, we analyzed bat rabies test results
      before and after introduction of raccoon variant rabies and after release of
      revised 1999 US Advisory Committee on Immunization Practices recommendations for
      rabies postexposure prophylaxis. Bat submissions were associated with level of
      rabies awareness and specific postexposure recommendations.

PMID- 20678327
TI  - Lyme borreliosis, Po River Valley, Italy.
AB  - We aimed to determine the presence of Ixodes ricinusticks in heavily populated
      areas of the Po River Valley after report of a Lyme disease case. Eighteen
      percent of ticks examined from 3 locations were positive for Lyme disease
      borreliae. Lyme disease was diagnosed for 3 workers at risk for tick bite.

PMID- 20678328
TI  - Pandemic (H1N1) 2009 Surveillance in Marginalized Populations, Tijuana, Mexico.
AB  - To detect early cases of pandemic (H1N1) 2009 infection, in 2009 we surveyed 303
      persons from marginalized populations of drug users, sex workers, and homeless
      persons in Tijuana, Mexico. Six confirmed cases of pandemic (H1N1) 2009 were
      detected, and the use of rapid, mobile influenza testing was demonstrated.

PMID- 20678329
TI  - Novel Mycobacterium tuberculosis complex pathogen, M. mungi.
AB  - Seven outbreaks involving increasing numbers of banded mongoose troops and high
      death rates have been documented. We identified a Mycobacterium tuberculosis
      complex pathogen, M. mungi sp. nov., as the causative agent among banded
      mongooses that live near humans in Chobe District, Botswana. Host spectrum and
      transmission dynamics remain unknown.

PMID- 20678330
TI  - Quarantine methods and prevention of secondary outbreak of pandemic (H1N1) 2009.
AB  - During the 2009 influenza (H1N1) pandemic, some countries used quarantine for
      containment or mitigation. Of 152 quarantined university students we studied,
      risk for illness was higher for students quarantined in a room with a person with
      a confirmed case; we found no difference between students quarantined in double
      or single rooms.

PMID- 20678331
TI  - Picornavirus salivirus/klassevirus in children with diarrhea, China.
AB  - To learn more about salivirus/klassevirus, we tested feces of children with
      diarrhea in China during 2008-2009. We isolated the virus from 9/216 diarrhea
      samples and 0/96 control samples. The nearly full polyprotein of 1 isolate, SH1,
      showed 95% identity with a salivirus from Nigeria, indicating widespread
      distribution and association with diarrhea.

PMID- 20678332
TI  - Human Rickettsia heilongjiangensis infection, Japan.
AB  - A case of Rickettsia heilongjiangensis infection in Japan was identified in a 35
      year-old man who had rash, fever, and eschars. Serum contained R.
      heilongjiangensis antibodies, and eschars contained R. heilongjiangensis DNA. R.
      heilongjiangensis was also isolated from ticks in the suspected geographic area
      of infection.

PMID- 20678333
TI  - Pandemic (H1N1) 2009 vaccination and class suspensions after outbreaks, Taipei
      City, Taiwan.
AB  - In Taipei City, class suspensions were implemented beginning September 1, 2009
      when transmission of pandemic (H1N1) 2009 infection was suspected. The uptake
      rate of pandemic (H1N1) 2009 vaccination (starting on November 16, 2009) among
      students 7-18 years of age was 74.7%. Outbreaks were mitigated after late
      November 2009.

PMID- 20678334
TI  - Pandemic (H1N1) 2009 virus and Down syndrome patients.
AB  - We compared prevalence of hospitalization, endotracheal intubation, and death
      among case-patients with and without Down syndrome during pandemic (H1N1) 2009 in
      Mexico. Likelihoods of hospitalization, intubation, and death were 16-fold, 8
      fold, and 335-fold greater, respectively, for patients with Down syndrome.
      Vaccination and early antiviral drug treatment are recommended during such
      epidemics.

PMID- 20678335
TI  - Household effects of school closure during pandemic (H1N1) 2009, Pennsylvania,
      USA.
AB  - To determine the effects of school closure, we surveyed 214 households after a 1
      week elementary school closure because of pandemic (H1N1) 2009. Students spent
      77% of the closure days at home, 69% of students visited at least 1 other
      location, and 79% of households reported that adults missed no days of work to
      watch children.

PMID- 20678336
TI  - Imported human rabies, the Philippines and Finland, 2007.

PMID- 20678337
TI  - Eye-opening approach to norovirus surveillance.

PMID- 20678338
TI  - Possible recurrent pandemic (H1N1) 2009 infection, Israel.

PMID- 20678339
TI  - Novel chlamydia-like organisms as cause of bovine abortions, UK.

PMID- 20678340
TI  - West Nile virus knowledge among Hispanics, San Diego County, California, USA,
      2006.

PMID- 20678341
TI  - Crimean-Congo hemorrhagic fever in man, Republic of Georgia, 2009.

PMID- 20678342
TI  - Mycobacterium avium subsp. hominissuis infection in horses.

PMID- 20678343
TI  - Lethal necrotizing pneumonia caused by an ST398 Staphylococcus aureus strain.

PMID- 20678344
TI  - Not-so-novel Michigan rabbit calicivirus.

PMID- 20678345
TI  - Leptospira serovar as prognostic factor.

PMID- 20678346
TI  - Not from the stars do I my judgment pluck.

PMID- 20678347
TI  - Editorial. Egas moniz, the pioneer of cerebral angiography.

PMID- 20678348
TI  - Editorial. Interventional neuroradiology and ethics.

PMID- 20678349
TI  - Transarterial embolisation of cerebral arteriovenous malformations. How few can
      you do?
AB  - SUMMARY: Arteriovenous malformations of the brain are rare disorders.
      Embolisation has emerged as an effective treatment with an acceptable, low
      complication rate. Previously presented results are completed with results from
      1994 to 1996. Ninety-six percent of the patients were treated with no or very
      minor sequelae resulting in total obliteration in 32% and supplementary
      stereotactic radiation in 49%. Ninety percent of all patients are in excellent or
      good health at follow up. These results may be jeopardised by the ongoing
      proliferation of endovascular treatment for AVMs.

PMID- 20678350
TI  - Endovascular approach to a ligated external carotid artery. Technical note.
AB  - SUMMARY: A 37-year-old female with left sided multiple congenital haemangiomata
      presented with repeated haemorrhage. The haemorrhagic origin was from the
      angiomatous lesion with arteriovenous (AV) shunting in the tongue and pharynx.
      The patient had already undergone ligation of the external carotid artery.
      Vascularization was mainly from the portion of the external carotid artery distal
      to the occlusion. Our first approach via the collateral channels to the
      haemangioma failed. Through direct puncture of the distal end of the external
      carotid artery with the use of two dimensional road mapping, we succeeded in
      catheterizing the distal end of the external carotid artery at the first attempt
      without placing any pressure on the neck, and carried out selective embolisation
      without mishap.

PMID- 20678351
TI  - Embolisation of Spinal Cord Arteriovenous Malformations with Glue through the
      Anterior Spinal Axis. Review of 20 Cases.
AB  - SUMMARY: We reviewed the clinical and morphological results of spinal cord
      arteriovenous malformations (SCAVMs) embolised with acrylic glue through the
      anterior spinal axis (ASA), and assessed the anatomical guidelines that should be
      followed to safely embolise the ASA. Twenty consecutive SCAVMS seen between 1982
      and 1996 were reviewed. There were 15 lesions in the thoracolumbar cord and 5 in
      the cervical cord. Haemorrhage was the revealing symptom in 13 patients (65%).
      Embolisation through the ASA was done in 19 SCAVMs (2 with PVA particles in our
      early experience and 17 with Histoacryl(*)). One patient was not embolised
      because of a spastic reaction of the ASA that led to secondary subtotal
      thrombosis of the SCAVM without neurological deficit. The ASA was chosen as
      arterial approach to the AVM because it was the only feeder to the lesion (1
      case) andlor because it was one of the accessible pedicles harbouring particular
      angioarchitectural weakness points. Vascular occlusion was always indicated and
      performed following precise anatomical analysis of the lesion and of the regional
      vascular disposition. In all cases embolisation of the ASA feeders to a SCAVM was
      performed under general anaesthesia, without any evoked potentials or provocative
      tests. However, 3/19 (16%) patients presented transient worsening of their
      clinical condition. Permanent morbidity occurred in 2/19 patients (11%): one
      patient cured from a cervical intramedullary AVM presents mainly a deltoid palsy,
      the other with a thoracic intramedullary AVM has worsened his paraparesis. At
      follow-up, 6/19 patients (32%) are neurologically normal and 10/19 (53%) have
      improved their neurological conditions and deficits. One patient embolised
      recently is currently stable but is expected to improve. No embolised patient
      bled or rebled during followup. Neurological symptoms recurred in one patient who
      had been stable for one year after his first embolisation. For an experienced
      interventional neuroradiology team, embolisation of SCAVMs through the ASA is
      feasible with acrylic glue with good clinical results. Proper analysis of the
      vascular architecture is mandatory to select the cases that can benefit from such
      approach.

PMID- 20678352
TI  - Sticky Platelet Syndrome: a Cause of Neurovascular Thrombosis and Thrombo
      embolism.
AB  - SUMMARY: Increased platelet aggregation induced by adenosine diphosphate and
      epinephrine and enhanced platelet activation response to surface contact are the
      key features of the "sticky platelet syndrome", in which the phenotype is
      transmitted with an autosomal dominant pattern. Two thirds of the patients with
      this syndrome have a positive family history of thrombo-embolic disease, which
      may be triggered by stress. We have seen two patients suffering from intracranial
      arterial and venous sinus thrombosis due to sticky platelet syndrome.
      Hyperaggregability of the platelets after stimulation with adenosine diphosphate
      and epinephrine was found in both. Case 1: A 43 year old man with a superior
      sagittal and right transverse venous sinus thrombosis developed subdural hygromas
      and a venous infarct of the parietal lobe. After burr hole evacuation of the
      hygromas, aspirin and phenoprocumone were prescribed. The patient made a good
      neurological recovery. Case 2: A 52 year old woman experienced spontaneous
      occlusion of a right MCA branch. The work-up revealed bilateral MCA and a basilar
      tip aneurysm. During the attempt to treat the basilar tip aneurysm by
      endovascular means, a thrombus formed within the left vertebral artery and was
      dislodged to both posterior cerebral arteries (PCAs). Local intra-arterial
      fibrinolysis yielded good recanalization of both PCAs. No new neurological
      deficit occurred. Continuous prophylaxis with aspirin was started. In sticky
      platelet syndrome stress and adrenaline release can trigger the thrombosis of
      intracranial arterial or venous vessels in otherwise healthy subjects. This is a
      potential cause of thromboembolic complications during endovascular procedures.
      Low-dose aspirin normalizes platelet hyperaggregability.

PMID- 20678353
TI  - Large haemangiopericytoma of the posterior cervical space. The role of imaging
      and therapeutic embolisation in the management of an unsuspected hypervascular
      head and neck neoplasm.
AB  - SUMMARY: We report a case of a 39-year old woman who upon developing a rapidly
      enlarging posterior cervical space tumour, underwent incisional biopsy prior to
      diagnostic imaging that resulted in nearly catastrophic haemorrhage.
      Subsequently, MR imaging showed evidence of marked hypervascularity, prompting
      diagnostic angiography and endovascular microembolization prior to surgical
      resection. The tumour turned out to be a large haemangiopericytoma arising from
      the paravertebral musculature. The case is instructive by highlighting the need
      for considering rare locations of hypervascular tumours in the head and neck
      region before attempting biopsy, which can be predicted by cross-sectional
      imaging studies, and the benefits of pre-operative devascularization with modern
      superselective microembolisation techniques.

PMID- 20678354
TI  - Endovascular Treatment of a Large Subclavian Pseudo-aneurysm. Case Report.

PMID- 20678355
TI  - Broad Neck Basilar Tip Aneurysm Treated by Neck Plastic Intra-aneurysmal GDC
      Embolisation with Protective Balloon.
AB  - SUMMARY: A 56-year-old male was found to have a basilar artery aneurysm by
      magnetic resonance imaging. Angiography demonstrated a broad neck basilar tip
      aneurysm. He refused surgical clipping but accepted intravascular embolisation.
      Introducing catheters were inserted into each of the bilateral vertebral
      arteries. A microcatheter was introduced into the aneurysm through one of the
      introducing catheters and a double lumen balloon catheter was introduced into the
      left posterior cerebral artery (PCA) through the other. The balloon was located
      from the left PCA to the basilar artery across the aneurysmal neck with the aid
      of a guidewire passed through the inner lumen of the balloon catheter. The
      balloon was inflated, and a Guglielmi detachable coil (GDC) was inserted until
      the platinum part was placed inside the aneurysm. The balloon was deflated to
      confirm the stability of the GDC, and then the GDC was electrically detached.
      This procedure was repeated until nine GDCs were successfully inserted. The
      aneurysm was tightly embolised despite its broad neck. Angiography comfirmed
      complete neck closure and stable preservation of the basilar artery and bilateral
      PCAs immediately, 1 week, 3 months, 6 months, and 12 months after embolisation
      without evidence of thrombo-embolic complications. Neck plastic intra-aneurysmal
      GDC embolisation using a protective balloon can be used to treat broad-neck
      aneurysms.

PMID- 20678356
TI  - Review of the literature. The leiden factor, a marker of the European population.

PMID- 20678357
TI  - A revised concept of the congenital nature of cerebral arteriovenous
      malformations.
AB  - SUMMARY: Cerebral arteriovenous lesions are in general considered to be
      congenital in nature despite the fact that there is no evidence that the AV
      shunts diagnosed in adults are present at birth in a similar format. Construction
      of a vascular structure is the result of complex biological influences starting
      in the embryo, and continuing in the foetus, the neonate and the young infant.
      This vascular tree has to be maintained, repaired and modified according to
      metabolic demands, requiring over time the renewal of the entire structure. This
      is also genetically programmed and controlled. Both construction and maintenance
      involve repetitive steps and feedback towards the vascular tree according to the
      demands. Alterations in the programme or in the cellular logistics to achieve it,
      will create a different construction of the blood vessel wall. Analysis of the
      origin of the cerebrofacial endothelial cell would suggest that, the earlier a
      causative event occurs the larger the area of impact, and the higher the chances
      of apparent multifocality will be. The later the trigger occurs the more focal
      the defect and the smaller the lesion. If so, growth of an AVM as such should not
      occur; large nidi will not result from the growth of smaller ones. The impact of
      Rendu-Osler-Weber (ROW) disease on the venous endothelial cells and the
      polymorphism observed in cerebral arteriovenous shunts in ROW patients may
      outline the role played by the veins as the primary target in the development of
      cerebral AVMs. The venous and arterial angiopathy related to chronic high flow
      (or flow changes beyond normal equilibrium) impact a normally reacting
      vasculature which has been "abnormally" triggered by an AVM. This intraluminal
      trigger represents a "stress trigger" which can be flow, pressure or "other"
      related factors. This interpretation identifies the so-called AVMs to be the
      expression of various diseases rather than the disease itself They are the result
      and negative impact of biological dysfunction of the remodelling process at the
      capillarovenous junction.

PMID- 20678358
TI  - Predictibility of the cervical origin of the anterior spinal artery.
AB  - SUMMARY: The anatomic study (under a surgical microscope) of 25 brains that had
      previously been injected with colored latex confirmed the fact that in the
      majority of cases, the anterior spinal artery results from the merging of two
      arterioles which both derive from two vertebral arteries. This bilateral nature
      is determined by the symmetric origin of the posterior inferior cerebellar
      arteries. When the conformation is asymmetrical, a single anterior spinal artery
      branches off from the vertebral artery that supplies the closest posterior
      inferior cerebellar artery.

PMID- 20678359
TI  - Making evidence available: prognostic classification systems.
AB  - SUMMARY: Claims of treatment selectivity can represent an important therapeutic
      advance: however, most such claims cannot be confirmed with independent data.
      This implies a management dilemma when confronted with ambiguous information on
      the risks of therapies and, most of all, insufficient criteria for identifying
      patients at risk. An accurate assessment of prognosis can help overcome the
      uncertainties facing the patients. But the identification of prognostic factors
      is subject to certain caveats. An essential part of prognostic factor analysis is
      standardization, a fact that is often overlooked. Thus, two different studies
      identifying the prognostic value of a factor may not be truly comparable, making
      a meaningful comparison difficult. Therefore, the development of an accurate
      prognostic system provides a method of conveying clinical experience to others
      without ambiguity.

PMID- 20678360
TI  - The natural history and management of intracranial dural arteriovenous fistulae.
      Part 1: benign lesions.
AB  - SUMMARY: The recently proposed classification scheme of Borden, Wu, and Shucart
      (Borden(*)) should have the ability to identify those intracranial dural
      arteriovenous fistulae (ICDAVF) which will continue to behave in a benign
      fashion. We examine for the first time the natural history of benign ICDAVF,
      including the predictive ability of this grading scale, and the implications for
      lesion management. A cohort of 55 Borden(*) grade I lesions was selected from a
      heterogeneous series of 102 consecutive lCDAVF seen at one institution between
      1984 and 1995. Data were collected prospectively from 1991. Grade 1 lesions were
      those whose nidus drained directly into a dural venous sinus (DVS) or meningeal
      vein. The absence of retrograde leptomeningeal venous drainage (RLVD) was an
      important feature. Intracranial haemorrhage (ICH), non haemorrhagic neurological
      deficit (NHND), and death were considered aggressive features. There were 23
      cavernous sinus, 2 foramen magnum, 1 middle cranial fossa, and 29 transverse
      sinus lesions. One patient received obliterative surgical treatment. Thirty-two
      lesions were observed only, and 22 patients developed symptoms or signs requiring
      palliative embolisation. Two minor complications occurred following embolisation:
      transient pulmonary aedema (1), and an asymptomatic pericallosal artery embolus
      (1). Follow-up was available on 48 (89%) patients for a total of 133 patient
      years (mean 33 months). This included 26 of the 32 patients observed and all 22
      of the patients embolised. Aggressive interval behavior was seen in only one
      patient. Symptom improvement or resolution was observed in the majority of
      patients, whether observed only [21/26 (81%) j, or whether they required
      embolisation for symptom palliation [19/22 (86%)). Overall, 53 of the 54 (98%) of
      ICDAVF behaved in a benign fashion in the follow-up period. The predictable
      benign natural history of patients identified as Borden(*) grade I at
      presentation mandates a conservative approach to these ICDAVF. In some patients,
      when symptom severity demands, palliative embolisation is an effective and safe
      therapy.

PMID- 20678361
TI  - The natural history and management of intracranial dural arteriovenous fistulae.
      Part 2: aggressive lesions.
AB  - SUMMARY: The natural history of aggressive intracranial dural arteriovenous
      fistulae (ICDAVF) is unknown. Despite this, the recently proposed classification
      scheme of Borden et al (Borden(*)) has the potential to predict aggressive lesion
      behavior after presentation for any lesion, but has so far been untested. In
      addition, they discuss a new but logical treatment strategy for aggressive ICDAVF
      based on the elimination of retrograde leptomeningeal venous drainage (RLVD). Our
      similar philosophy and substantial experience with these lesions, provides a
      unique opportunity to test these hypotheses. A cohort of 46 Borden(*) grade II
      and III ICDAVF was selected from a series of 102 ICDAVF seen at a single
      institution between 1984 and 1995. Patients with these lesions, presumed to have
      an aggressive course were all offered treatment. Conservative therapy was chosen
      by 14 (30%) patients, 22 (47%) had surgery, and 20 (43%) had embolisation either
      as sole treatment or prior to surgery. During the follow-up period (249 lesion
      months) for the conservatively treated group, Jour (29%) patients died. Excluding
      presentation, these patients were observed to have interval rates of intracranial
      hemorrhage (ICH), non haemorrhagic neurological deficit (NHND), and mortality, of
      19.2%, 10.9%, and 19.3% / lesion year respectively. The 11 patients who had
      embolisation alone were followed for a total of 344 months after treatment. All
      nine patients who had lesion obliteration, or subtotal obliteration with
      elimination of RLVD, as confirmed by angiography, experienced improvement or
      complete clinical recovery. Two patients had subtotal obliteration without
      elimination of RLVD. One died from interval ICH and the other experienced a
      delayed NHND. Twenty-five surgical operations were performed on 23 ICDAVF in 22
      patients. Resection of the ICDAVF was performed in 9 patients, and 16 patients
      were treated with surgical disconnection alone. Complications occurred in 3/9
      (33%) patients who had their lesions resected and none of the disconnected group.
      Failure to achieve angiographic obliteration of RLVD in 2 patients treated with
      resection was associated with an adverse outcome in both cases (death, and
      interval NHND). All 16 (100%) of the disconnected group were shown to have
      undergone angiographic obliteration with excellent clinical outcome. Untreated,
      Borden(*) grade II and III ICDAVF have a poor natural history. Also, persistence
      of RLVD after inadequate treatment results in adverse outcomes. Embolisation
      usually improves the safety of surgical access and may lead to obliteration on
      its own in some cases. For the aggressive ICDAVF, surgery is required in most
      cases, and our data confirm that surgical disconnection alone results in cure of
      all Borden(*) grade III ICDAVF, and in grade II lesions, ifnot cure, conversion
      to a benign grade I lesion.

PMID- 20678362
TI  - Editorial comment on davies' papers. Angioarchitecture and natural history of
      dural arteriovenous shunts.

PMID- 20678363
TI  - Giant Multilocular Fusiform Aneurysm of the Posterior Cerebral Artery. Report of
      a Case Treated by Parent Artery Occlusion Together with Intra-aneurysmal
      Embolisation.
AB  - SUMMARY: A 60-year-old woman presented with a giant posterior cerebral artery
      aneurysm. Her visual field examination revealed right upper quadrantanopia.
      Because of the difficulty of the neck clipping, we performed parent artery
      occlusion using the Guglielmi detachable coils following balloon Matas test
      monitored with single photon emission computed tomography (SPECT) with 99mTc-d, I
      hexamethyl-propylene-amine oxime. Postoperative left internal angiography showed
      the left occipital region was supplied by a leptomenigeal collateral via left the
      middle cerebral artery. Six months after embolisation the aneurysm was completely
      thrombosed on MR imaging. Her visual field deficits had also improved six months
      after embolisation. A combination of the balloon Matas test with SPECT followed
      by parent artery occlusion is an excellent method to treat such giant aneurysms.

PMID- 20678364
TI  - Bilateral thalamic infarcts complicating basilar tip aneurysm coil embolisation.
      A result of unilateral perforating artery occlusion.
AB  - SUMMARY: We report a case of bilateral thalamic infarcts with no apparent cause
      other than unilateral partial occlusion of the P1 segment of the posterior
      cerebral artery caused by Guglielmi detachable coils in a basilar tip aneurysm.
      This case demonstrates that bilateral thalamic infarctions can result from a
      unilateral posterior cerebral artery stenosis or occlusion, and does not
      necessarily imply bilateral posterior cerebral artery abnormality.

PMID- 20678365
TI  - Treatment of an arteriovenous shunt draining into a venous angioma by selective
      embolisation. A case report.
AB  - SUMMARY: We treated a 62-year-old woman who suffered from intraventricular
      haemorrhage. Angiography revealed an arteriovenous shunt draining into a venous
      angioma. She was successfully treated by obliteration of the arteriovenous shunt
      with transarterial embolisation. Angiography performed after embolisation
      demonstrated that the persisting venous angioma served as the draning vein for
      normal middle cerebral artery perfusion. We believe that selective arterial
      occlusion with preservation of the venous component is the best treatment for
      this type of mixed vascular malformation.

PMID- 20678366
TI  - Endovascular treatment of a ruptured intracranial arterial aneurysm in a 12-year
      old child with recessive polycystic kidney disease.
AB  - SUMMARY: A 12-year-old boy with recessive polycystic kidney disease and
      congenital hepatic failure, presented intracranial subarachnoid haemorrhage, due
      to the rupture of a laterobasilar tip aneurysm. In addition, he presented a left
      sided middle cerebral unruptured aneurysm demonstrated during the screening
      procedure. Our patient is a boy, like most children with intracranial aneurysms,
      but differs from children with intracranial aneurysms in polycystic kidney
      disease. The age of bleeding was low (actually the second youngest case
      reported), with a good Hunt and Hess grade at admission. The localization of the
      aneurysm is exceptionally posterior (laterobasilar tip); in our case as
      intracranial aneurysms can be multifocal at that age. Renal function and blood
      pressure were normal. The endovascular GDC approach achieved a good result and
      excellent clinical outcome. Although most of what is known in this disease
      belongs to the autosomal dominant form, it is unclear whether the risk of a
      demonstrated un ruptured intracranial aneurysm is the same as the risk of SAH
      from a non demonstrated one. It even seems that bleeding during follow-up in
      patients with polycystic kidney disease mostly occurs from non previously
      demonstrated intracranial aneurysms(9).

PMID- 20678367
TI  - Editorial. Statistics in medicine.

PMID- 20678368
TI  - Glued Catheters during Embolisation of Brain AVMs with Acrylic Glue.
AB  - SUMMARY: We evaluated the frequency and the side effects associated with gluing a
      piece of microcatheter in the feeder during embolisation of brain AVMs with
      acrylic glue. A retrospective analysis of 233 brain AVMs embolised with acrylic
      glue over a 15 year period has shown that 29 microcatheters were glued into the
      feeder. This represents 936 superselective catheterizations of different feeders
      followed by injection of glue. There was no side effect in 27 cases. Eight cases
      were operated upon a few hours or days after the complication occurred. The piece
      of tubing was removed in six cases. The reason for early surgery was the fear of
      extensive thrombosis of a major trunk (MCA or BA) or taking advantage of the
      catheter being still free in the cerebral vessel. In one case of temporal AVM, a
      Magic 1.5F coiled up into the distal basilar and PCA. In one case of left
      parietotemporal AVM, surgery was done one month after having glued a piece of
      tubing into the left MeA without side effect. The patient became hemiplegic and
      aphasic two hours after surgery. The thrombosed left MeA was reopened with
      Urokinase. The patient recovered with minor residual aphasia. The risk of side
      effects increases with the use of the Magic 1.5F that coils up into the vessel
      more easily than the Magic 1.8F. Leaving a piece of Magic catheter in the feeder
      to a brainAVM usually has no side effect. When there is a risk of thrombosis of a
      major trunk (MCA, BA) or when surgical resection is indicated, surgery should be
      done as soon as possibile because it is usually possible and easy to retrieve the
      piece of tubing from the intracranial circulation. The frequency of this
      complication has decreased since we starded using more diluted acrylic glue.

PMID- 20678369
TI  - The "Remodelling Technique" in the Treatment of Wide Neck Intracranial Aneurysms.
      Angiographic Results and Clinical Follow-up in 56 Cases.
AB  - SUMMARY: The main factor limiting endovascular treatment of intracranial
      aneurysms is the shape of the aneurysmal sac, particularly the width of the neck.
      In this study we present a new technique to occlude wide neck aneurysms that
      involve the temporary inflation of a non-detachable balloon in front of the
      aneurysm neck during each coil placement. The aim of the study is to present the
      feasibility, efficacy and safety of this "remodelling technique" (RT) compared to
      that of "normal" GDC treatment. We selected 56 aneurysms in 54 patients for
      treatment with the RT. Thirty-seven (70%) of the patients presented with
      subarachnoid haemorrhage. Twenty-five (45%) of the aneurysms were located at the
      vertebrobasilar artery, 24 (43%) at the internal carotid artery, and seven at the
      level of smaller arteries. Treatment was achieved in 52 aneurysms in 50 patients.
      Two aneurysms which were initially not completely occluded underwent a second
      treatment using the RT. Final results (i.e. the last follow-up angiography or
      results at the end of the treatment for the cases that have not yet had follow
      up) consisted of total occlusion in 40 cases (77%), subtotal occlusion in nine
      cases (17%), and incomplete occlusion in three cases (6%). Angiographic evidence
      of clotting was observed during the procedure in three cases, resulting in one
      permanent deficit (quadranopia). Rupture of the aneurysmal sac occurred during
      the procedure in three cases, all of which were asymptomatic in the follow-up.
      Thus, morbidity due to the technique was 1/52 (1%) and mortality was 0/56
      patients. The remodelling technique allowed the treatment of 52 wide neck or
      badly shaped aneurysms that were not treatable without this technique. The
      results of occlusion with the RT seem better than those in our series of normal
      GDC treatment, and complications related to the technique are fewer. This
      technique thereby extends the spectrum of treatable aneurysms without increasing
      the risk incurred by treatment.

PMID- 20678370
TI  - Seizures in cerebral arteriovenous malformations: type, clinical course, and
      medical management.
AB  - SUMMARY: We investigated the type and early clinical course of seizure disorders
      in cerebral arteriovenous malformations (AVMs). Decisions on invasive treatment
      for AVMs depend on detailed knowledge of the natural course and prognosis of
      neurologic sequelae. Among 328 patients of a prospective cerebral AVM databank 92
      (28%) presented with seizures unrelated to haemorrhage. Under a median
      observation time of 2.2 years (mean 3.8 years) the 92 patients received 454
      follow-up examinations (median time interval 4.6 months). All patients were
      treated with anticonvulsant medication. During the observation period sixty (65%)
      patients received staged endovascular glue embolisation. The effect of staged
      embolisation on seizure recurrence was tested univariately by comparing patients
      undergoing embolisation versus those without endovascular treatment. At the time
      of enrolment in the database, elementary (motor or sensory) and partial complex
      seizures were described in twenty (22 %) and one (1%) patients, respectively.
      Generalized seizures without focal initiation were reported in sixty (65%) and
      with focal initiation in 11 (12%) patients. 57 (62%) cases had suffered a seizure
      as a first single event, ten (11%) had weekly, 17 (19%) monthly, and eight (9%)
      patients had seizures once per year. In the following clinical course, complete
      cessation of seizure activity was seen in 69 (75%). Ten (11%) patients continued
      to have seizures at a rate of once per year or less. 13 (14%) cases continued to
      have weekly to monthly events with only four (4%) of them showing (monthly) grand
      mal. An early beneficial effect of staged embolisation on seizure recurrence was
      not observed. Seizure disorders in cerebral AVMs show a benign early course,
      leaving few patients with insufficient seizure control. The differential longterm
      effect of invasive AVM treatment on seizure control should be subject to clinical
      trials.

PMID- 20678371
TI  - The arithmetics of risk.
AB  - SUMMARY: In the following note the basic principles of event data analysis and
      censored data will be explained. The concept of risk will be defined. The
      interaction of estimation and confidence interval will be discussed. We explain
      the estimator of risk and show how to use it for the calculation of probability
      statements. An example is given to make the formal statements more explicit. We
      define the KaplanMeier estimator and compare it to the risk concept. Two common
      fallacies in risk assessment are discussed.

PMID- 20678372
TI  - Embolisation of Ruptured Cerebral Aneurysms with Interlocking Detachable Coils in
      Acute Stage. Acute IDC Embolisation for Ruptured Aneurysms.
AB  - SUMMARY: Twelve cases of ruptured cerebral aneurysm were treated in acute stage
      with interlocking detachable coils (IDC, Target Therapeutics, Fremont,
      California) and the outcome was assessed. IDCs were placed intra-aneurysm for
      intraaneurysmal occlusion, or intra-artery for proximal occlusion. CASES: age 36
      84 (mean; 60) y.o., 11 females and 1 male; 1, 5, 4 and 2 patients were
      categorised (Hunt and Hess) as grades 1, 2, 3 and 4 respectively. An intra
      aneurysmal occlusion in ten cases and a proximal occlusion in two were performed
      on day 1-11 (mean 4). On angiograms and CT findings, the ruptured point seemed to
      have occluded in all cases. The occlusion rate was 100% in five cases, 95% in
      two, 90% in three, 80% in one, and less than 50% in one. There were two cases of
      technical complication, one a coil migration and the other an aneurysmal
      perforation with IDC. Their Glasgow Outcome Scale six months after embolisation
      was graded as good recovery in four cases, moderately disabled state in two,
      severely disabled state in one, and dead in five. Follow-up angiograms taken four
      to six months after embolisation showed an intra-aneurysmal coil compaction in
      five cases. Two of these were treated by a second embolisation or by neck
      clipping followed by aneurysmal resection, but another two were observed without
      any treatment and the last one died of rebleeding. Histological examination of
      the resected embolised aneurysm revealed slight organization around coils but no
      endothelialisation over the aneurysmal orifice. In our experience, coil
      embolisation with IDC for acute ruptured aneurysm is a promising means of
      preventing rerupture during subacute stage.

PMID- 20678373
TI  - An evaluation of the Physical Properties of Current Microcatheters and
      Guidewires. The Development of the "Catheter-glide Approach" in Response to
      Weaknesses of Current Materials.
AB  - SUMMARY: The physical properties of the 16 microcatheters and 7 guidewires
      currently available were evaluated to assess their manoeuvrability. This
      investigation included the latest varieties of these products. The test results
      showed that there was a wide variation in flexibility and friction between the
      distal segments of the catheters. Even the recently developed hydrophilic polymer
      coated catheters show this variation. Comparisons between guidewires also showed
      differing degrees of flexibility and friction. Torque transmission was also a
      variable factor. A combination of the most flexible microcatheter with the lowest
      friction and the most responsive guidewire with the lowest friction was picked
      for clinical evaluation. The effectiveness and safety of this combination of
      equipment was proved by embolising various cerebral arteriovenous malformations(
      AVMs) and thrombolysing cerebral emboli of arteriosclerotic patients. However it
      remains difficult to reach the nidus of distally located AVMs with extremely long
      and tortuous feeding pedicles such as parietal lobe AVMs. The efforts to overcome
      the weaknesses of current materials by further improving equipment and technique
      is another subject of the current paper.

PMID- 20678374
TI  - Expansion of a haematoma after urokinase thrombolysis of superior sagittal sinus
      thrombosis.
AB  - SUMMARY: Thrombosis of the superior sagittal sinus may result in significant
      morbidity and recently up to 20% mortality, Primary treatment has consisted of
      anticoagulation and methods for controlling increased intracranial pressure. The
      development of interventional neuroradiologic techniques has enabled infusion of
      thrombolytics at the clot. We describe a woman with a cerebral haemorrhage due to
      a thrombosed superior sagittal sinus. Her decreased level of consciousness and
      increasing hemiparesis prompted direct thrombolytic therapy (urokinase). Flow was
      restored in the occluded sinus, but an acute expansion of the haematoma an hour
      after conclusion of the infusion resulted in temporary worsening of her
      neurologic deficits. Although the ultimate outcome was satisfactory, the
      possibility of further intracranial bleeding must be balanced against the risk of
      death with conservative therapy.

PMID- 20678375
TI  - Treatment of a Small Hole Post-traumatic Carotid-Cavernous Fistula with a Non
      Detachable Balloon Catheter. A Technical Note.
AB  - SUMMARY: Transarterial detachable balloon embolisation has become a well
      established primary treatment of post-traumatic carotid cavernous fistula (CCF)
      (1-3). However, in some instances due to the complexity of the fistula, the
      treatment can be difficult or impossibile. A simple and useful technique using a
      non-detachable balloon catheter to easily navigate the riilcrocatheter into the
      fistula via the transarterial route is discussed in this paper. The non
      detachable balloon catheter allows easy navigation of the micro catheter into the
      small hole fistula, and complete occlusion of the fistula was obtained using one
      interlocking detachable coil (IDC) in the draining veins. The method of using a
      non-detachable balloon catheter to navigate a micro catheter into a fistula is
      relatively easy via the transarterial route.

PMID- 20678376
TI  - Review of the Literature. Super-selective Chemotherapy with High Dose Carboplatin
      for Advanced Cervicofacial Tumours. Treatment Validation and Preliminary Findings
      in 22 Patients.
AB  - SUMMARY: Traditional treatment based on surgery combined with radiotherapy for
      stage III and IV cervicofacial squamous cell carcinomas has shown disappointing
      results to date. In the past, systemic chemotherapy was only used as a palliative
      treatment. Intra-arterial chemotherapy offers theoretical advantages mainly
      linked to increased drug tolerability. This new technique seems particularly
      suited to the management of squamous cell carcinomas in view of the local and
      regional spread of these tumours and the improved access by means of angiographic
      adminstration through the branches of the external carotid artery. We describe
      our experience of intra-arterial chemotherapy in 22 patients with biopsy-proven
      squamous cell carcinoma at the onset of disease. High dose Carboplatin (300-350
      mg/m(2)) was super- selectively injected by rapid infusion repeated in three
      sittings at two week intervals. The optimum point of drug infusion was determined
      in each patient on the basis of angiographic information obtained in the
      diagnostic work-up. The dual objective was to get as near as possible to the
      primary tumour and to infuse the drug into any satellite lymph node metastases.
      The narrow calibre and tortuous course of the branches of the external carotid
      artery increase the likelihood of vasospasm: 5F hydrophilic catheters proved very
      useful to minimize technical complications in all angiographic procedures
      performed (64). Treatment was always well tolerated with mild local toxicity
      (grade 1-3, WHO), mainly involving the mucosae (stomatitis) and skin (dermatitis
      and alopecia) and minimum myelosuppression (grade 1-2, WHO). A positive response
      (complete or partial tumour remission) was observed in 94% of patients with
      primary tumours and in 50% of cases with cervical lymph node metastases. The
      reduction in tumour size often precluded the need for surgery and the cycles of
      chemotherapy were followed only by target radiotherapy for the tumour residue.

PMID- 20678377
TI  - Letter to the editor.

PMID- 20678378
TI  - Characteristics of a New Liquid Material for Arteriovenous Malformations (HEMA
      MMA).
AB  - SUMMARY: Characteristics of a newly developed liquid material for embolization of
      AVM and its clinical experiments are reported. This liquid is composed of
      dissolving poly (2-hydroxyethyl methacrylate-co-methyl methacrylate) in Iopamiron
      with adding a small amount of ethyl alcohol. Thirty-two cases of AVM and 5 cases
      of spinal AVM were embolized with this liquid with good results. This liquid
      material is of low viscosity, not adhesive and not cytotoxic, therefore, it can
      be easily injected through a microcatheter, and can safely and effectively
      occlude AVM.

PMID- 20678379
TI  - Covered stent placement for artificial cervical carotid aneurysms. Experimental
      study.
AB  - SUMMARY: In order to evaluate the midterm patency and the effectiveness of Dacron
      covered self-expanding metallic stent in the treatment of cervical carotid
      aneurysm, we made wide-necked carotid aneurysms with a technique of vein pouch
      end-to-side anastomosis, and implanted the stents percutaneously to occlude the
      aneurysms in dogs. The patency was angiographically followed up for 3 months with
      anticoagulation and antiplatelet medications. The Dacron-covered stent could make
      the aneurysms disappear angiographically within ten minutes if it was implanted
      in the correct place. The acute thrombotic obstruction was seen in one of the
      five regions. The delayed stenosis was seen in two of the five regions in two
      weeks. Only one of the five regions was patent three months after the stent
      placement without stenosis. In this case, no cerebral infarction of the brain was
      found histologically. The Dacron-covered stent can make wide-necked aneurysms
      occlude quickly. However, the short or midterm patency was poor, suggesting that
      it is not safe enough to be used clinically in carotid lesions. Further study
      should be needed to improve the materials for a covered stent before clinical
      applications.

PMID- 20678380
TI  - Interventional neuroradiology in hemifacial spasm. Diagnostic and therapeutic
      implications.
AB  - SUMMARY: There have never been functional studies in the diagnosis of hemifacial
      spasm caused by neurovascular compression. We used neurointerventional techniques
      to conduct a functional investigation of the artery responsible for hemifacial
      spasm in seven patients. A microcatheter was inserted into the various arteries
      of the posterior circulation under systemic heparinization, and its effect on the
      spasm was evaluated clinically and electromyographically. In six patients who
      underwent microvascular decompression surgery, the vessels compressing the root
      exit zone of the facial nerve were surgically determined, and compared with the
      result of the procedure. The catheter was inserted into twelve arteries. The
      spasms were stopped immediately and completely by the insertion of the catheter
      into seven arteries. Six of them were surgically proven to compress the root exit
      zone of the facial nerve. The spasm was changed in frequency or in type by the
      insertion into two arteries. These arteries were also compressing the root exit
      zone. One artery was located at a more peripheral part of it and the other was
      running over another artery compressing the root exit zone. The spasms were not
      affected at all by the insertion into three arteries. These arteries were not
      observed in the operative field and had no contact with the nerve. Superselective
      angiograms showedpositional qnd configurational changes of the arteries. There
      was no arterial spasm and tight catheterization leading to stasis of contrast
      material within the arteries. There were no complications related to the
      procedures. Functional relationship between the artery and the spasms was
      established in all the patients, and one patient refused surgery because the
      frequency of the spasm was reduced by the procedure. The result of this study may
      suggest that a functional investigation of hemifacial spasm is feasible and seems
      useful for selecting good candidates for microvascular decompression surgery.

PMID- 20678381
TI  - Determining the Optimal Fluoroscopic View during Aneurysmal Embolization with
      Rotation DSA.
AB  - SUMMARY: To prevent coil protrusion into the parent artery, the fluoroscopic view
      during coil packing is quite important. However it is not always easy to find out
      the optimal fluoroscopic view. We applied a rotation DSA to predict the optimal
      fluoroscopic view for the endovascular treatment of 4 cases with a cerebral
      aneurysm. Since the trajectory of the C-arm is restricted within 60 degrees only
      around the patient's head and the number of DSA shots are limited rather than
      conventional DSA, we employed three dimensional CT angiography (3D-CT
      angiography) to focus the range of C-arm rotation. Rotation DSA proved quite
      useful to determine the optimal fluoroscopic view, when combined with
      preestimation by 3D-CT angiography.

PMID- 20678382
TI  - Percutaneous transluminal angioplasty for intracranial arteriosclerotic lesions.
AB  - SUMMARY: Recent developments of the interventional neuroradiological technique
      made percutaneous transluminal angioplasty (PTA) possible even for intracranial
      arteries(1). We report our experiences of 17 cases treated by PTA including 9
      intracranial internal carotid (ICA), 4 middle cerebral (MCA) and 4 vertebro
      basilar arterial (VBA) stenoses and discuss the problems of the procedure. All
      patients had cerebral ischemic symptoms and stenoses more than 60% calculated
      angiographically. Three of them were treated by PTA for residual stenoses after
      thrombolytic therapy for acute occlusion. We used PTA balloon catheters 2.0 mm to
      3.5 mm in diameter (Stealth, Target therapeutics) for all PTA procedures. A PTA
      balloon was inflated for 1 min at 6 atm as a rule. All were successfully dilated
      (stenosis less than 50%) except one treated by PTA for residual MCA stenosis
      after thrombolytic therapy. The patient died from massive infarction due to MCA
      re-occlusion caused by MCA dissection. Restenosis appeared in 4 of 16 patients.
      Repeated PTA was successfuly carried out for the 4 patients. However, restenosis
      appeared in one of them but the patient is now on follow-up because of
      asymptomatic course. PTA for intracranial arteries is an effective treatment but
      its indication should be determined strictly because of potential risk such as
      acute occlusion derived from dissection.

PMID- 20678383
TI  - Direct PTA for Acute Ischemic Stroke.
AB  - SUMMARY: We have performed direct PTA for 23 patients with acute ischemic stroke.
      Occlusion was identified at extracranial internal carotid artery (ICA) in 6
      patients, at extracranial vertebral artery (VA) in I, at intracranial ICA in 3,
      at middle cerebral artery (MCA) in 12, and at basilar artery (BA) in 1. Stenosis
      was identified at extracranial VA in 1 patient. In 4 of 6 patients of
      extracranial ICA, 1 of 1 patient of extracranial VA, 1 of 3 patients of
      intracranial ICA, 7 of 12 patients of MCA and 1 of 1 patient of BA,
      recanalization was observed. Fourteen of 22 occluded arteries (64%) were
      recanalized. The recanalization rate approximated that of local intraarterial
      fibrinolytic therapy. We have not experienced complications with this procedure.
      Direct PTA is promising and might be a novel recanalization technique.

PMID- 20678384
TI  - Angioplasty of acute occluded cerebral arteries.
AB  - SUMMARY: 22 cases of stenosed or occluded cerebral arteries were treated by
      percutaneous transluminal angioplasty (PTA) in acute stage. There were 10
      internal carotid lesions, 4 middle cerebral artery lesions, 5 intracranial
      vertebral artery lesions, and 3 basilar artery lesions. 14 cases were treated for
      residual stenosis after recanalization using urokinase. Successful dilatation
      (over 50%) was achieved in 16 cases (73%).3 lesions were inaccessible due to
      atherosclerotic change. There were no major complications. Restenosis was
      observed in 4 internal carotid lesions and 1 middle cerebral lesion. 7 (50%)
      cases with internal carotid lesions and 5 (63%) cases with vertebrobasilar
      lesions returned to their previous life. The results suggest that PTA in acute
      stage is feasible for occlusive disease of cerebral arteries.

PMID- 20678385
TI  - Stenting for extracranial stenotic lesions of carotid and vertebral arteries.
AB  - SUMMARY: We evaluated the feasibility of stenting in four patients. Two cases
      were vertebral osteal stenosis and the others were carotid stenosis at high
      position with ulcers. We placed balloon expandable coronary stents by a bared
      stent technique. The mean preprocedural stenosis (86.58%) was reduced to 13.05%.
      Patients were examined clinically and angiographically at 1,3 and 6 months after
      stenting. There was no minor nor major stroke during and after the procedures.
      Asymptomatic restenosis occurred in the cases of proximal vertebral arteries. One
      of these patients needed to repeat balloon dilatation. There were no angiographic
      restenoses in the location of stenting in the carotid artery. In the treatment
      for atherosclerotic stenoses, stent placement is a feasible and safe method.
      However restenosis in a vertebral osteal lesion should be carefully followed
      after stent placement.

PMID- 20678386
TI  - Carotid and vertebral stenting: preliminary report.
AB  - SUMMARY: We report our initial experience of carotid and vertebral stenting.
      Three haemodynamically significant extra-cranial lesions (% diameter stenosis >
      70) in 3 clinically symptomatic patients were treated by stenting between March
      1996 and September 1996. Two lesions of the internal carotid arteries were ostial
      and in one case a subtotal stenosis and ostial lesion of the vertebral artery
      were observed. All lesions looked more widely and smoothly dilated by stenting
      than by ordinary standard balloon angioplasty.

PMID- 20678387
TI  - Intra-arterial Thrombolytic Therapy for Acute Vertebrobasilar Artery Occlusion.
AB  - SUMMARY: We report on the results of intra-arterial thrombolysis in 11 patients
      with vertebrobasilar artery occlusion treated within 6 hours after onset of
      symptoms. Urokinase (5 patients) or recombinant tissue plasminogen activator (t
      PA) (6 patients) was injected through a microcatheter conducted to the thrombus.
      Eight patients showed recanalization of the thrombus. The outcome was excellent
      in 5 patients, good in 2 patients, and poor in one patient. Recanalization could
      not be achieved in 3 of the 11 procedures; all patients in whom recanalization
      failed died. There were no hemorrhagic complications after thrombolysis. Two
      patients with residual stenosis after thrombolysis underwent successful
      percutaneous transluminal angioplasty (PTA) to prevent reocclusion. Intra
      arterial thrombolysis for vertebrobasilar artery occlusion is a safe and
      effective treatment if it is performed within 6 hours.

PMID- 20678388
TI  - Reperfusion therapy for acute vertebrobasilar occlusion.
AB  - SUMMARY: We reviewed retrospectively our experience in treating 10 patients with
      acute vertebrobasilar occlusion. Nine patients were treated with interventional
      reperfusion therapy and the remaining one patient with top of the basilar
      embolism was treated conservatively because of deep coma and decerebrate rigidity
      with severely reduced cerebral blood flow (CBF) in the brain stem. Among 9
      patients with reperfusion therapy, 8 patients underwent intra-arterial
      thrombolytic therapy and the other one patient had direct percutaneous
      transluminal angioplasty (PTA). Eight patients had basilar artery occlusion, 1
      patient treated with direct PTA had bilateral intracranial vertebral artery
      occlusion and the other patient had left posterior cerebral artery occlusion
      presumably preceding top of the basilar embolism. In 4 of 10 patients, residual
      CBF was evaluated by single photon emission computed tomograpy (SPECT).
      Successful recanalization with clinical improvement was achieved in 6 of 9
      patients (66.7%) treated with reperfusion therapy. In patients with progression
      or fluctuation of incomplete brain stem syndrome, SPECT revealed preserved
      residual CBF and successful recanalization with clinical improvement was achieved
      by interventional reperfusion therapy. On the other hand, in patients with
      persistent deep coma and decerebrate rigidity, SPECT revealed marked reduction of
      residual CBF in the brain stem and recanalization could not improve clinical
      outcome. Preoperative SPECT may be useful to make a decision whether rep er
      fusion therapy should be performed or not in case of vertebrobasilar occlusion.

PMID- 20678389
TI  - Angiographic A-V Shunt during Interventional Thrombolysis for Acute Cerebral
      Embolism. A New Predictive Sign for Hemorrhagic Complication.
AB  - SUMMARY: In order to predict the post-therapeutic hemorrhagic complication of
      interventional thrombolysis, we retrospectively examined angiographic findings
      and other factors in 44 patients with acute cerebral embolism. All patients were
      super selectively catheterized within 5 hours of onset and received a fixed
      regimen of urokinase or t-PA, unless recanalization was achieved or deterioration
      was apparent before total infusion. Immediate post-therapeutic CT scan revealed
      hematoma within the basal ganglia in 10 patients (group 1) and no hemorrhage in
      the remaining 34 (group 2). A series of angiograms during the therapy showed A-V
      shunt from lenticulostriate arteries to thalamostriate vein in 7 of 10 cases in
      group 1; no case in group 2 was accompanied by such abnormal shunt. Prognosis
      after the therapy was worse in group 1 than in group 2. No other factors, such as
      therapeutic timing after the disease onset or total doses of urokinase or t-PA
      infused, differed between the two groups. These findings indicate that
      angiographic A-V shunt during therapy is a predictive sign of a high incidence of
      hemorrhagic complication. We recommend performing several angiographic controls
      during therapy and when A-V shunt is detected, the therapy should be discontinued
      to prevent hemorrhage which leads to a poor prognosis.

PMID- 20678390
TI  - Endovascular stenting of the cervical internal carotid artery.
AB  - SUMMARY: The purpose of this study was to determine the value of stenting in the
      treatment of occlusive vascular disease involving the cervical internal carotid
      artery. Clinical and angiographical results of stenting were compared those of
      conventional angioplasty alone up to 20 months of follow-up. The Palmaz-Schatz
      stent was implanted in two patients with acute intimal dissection, whereas
      conventional angioplasty alone was performed in seven patients with
      arteriosclerotic stenosis. Initial procedural success was achieved in all the
      patients, and acute or subacute complications were not encountered at all. One of
      the patients (14%) treated with conventional angioplasty alone developed late
      restenosis at three-month follow-up. The patients treated with stenting revealed
      satisfactory results clinically and angiographically. The present results may
      suggest that stenting is an effective and safe method to treat dissection of
      cervical internal carotid artery, but larger clinical trials as well as
      experimental studies would be necessary to define the indications and refine the
      stents.

PMID- 20678391
TI  - Intravascular ultrasound image system for experimental implantation of various
      stents. Part 1.
AB  - SUMMARY: This report describes the experiments we have conducted with an
      ultrasound image system (IVUS) and a three-dimensional intravascular ultrasound
      image system (3-D IVUS), to examine where and how vascular stents should be
      applied in the lesion, as a step towards mastering the techniques of this
      therapeutic approach. Based on the IVUS findings, it appears to be of importance
      to select an appropriate type of stent, and the indiscriminate application of
      stents must be avoided, except in emergency cases.

PMID- 20678392
TI  - Cavernous dural arteriovenous fistulas. Transvenous approach and venous drainage
      of the fistula.
AB  - SUMMARY: In transvenous endovascular treatment of dural arteriovenous fistula
      (AVF), access to the affected sinus is determined by venous drainage. In
      cavernous dural AVF, the route to the cavernous sinus is through the inferior
      petrosal sinus (IPS) or the superior ophthalmic vein. Other venous routes are not
      practical. Occlusive change of the IPS is a common finding. The transfemoral
      approach is not always easy because of obliteration of the IPS. In selection of
      the approach for the transvenous treatment of the cavernous dural AVF, these
      occlusive changes should be considered.

PMID- 20678393
TI  - Pitfalls in endovascular treatment of dural arteriovenous fistulas involving the
      cavernous sinus.
AB  - SUMMARY: Angiographic changes of the sylvian veins, superior ophthalmic vein
      (SOV), and superior petrosal sinus (SPS) before and after endovascular treatment
      were determined for 18 patients with dural arteriovenous fistulas (AVFs)
      involving the cavernous sinus, and pitfalls of endovascular treatment, especially
      regarding venous drainage routes, for 3 of the patients were reported. Case 1: 57
      year-old woman who presented with right abducens nerve palsy had a Barrow type D
      fistula in the right cavernous sinus draining into the bilateral inferior
      petrosal sinuses (IPS). One of the ipsilateral sylvian veins that had drained
      antegradely before treatment was occluded, and a small lacunar infarction in the
      corona radiata developed after transvenous embolization (TVE) of the right
      cavernous sinus. Case 2: 72-year-old woman who presented with symptoms of right
      ocular hypertension had a type D fistula in the right cavernous sinus draining
      into only the ipsilateral SOV. Conjunctival hyperemia persisted and was
      aggravated after angioanatomical obliteration of the fistula by transarterial
      embolization. Case 3: 55-year-old man who presented with left abducens nerve
      palsy had a type D fistula in the left cavernous sinus draining into the
      ipsilateral IPS and sylvian vein. The dural AVF was obliterated once with TVE,
      but recurred 1 week later with retrograde drainage into the ipsilateral SPS and
      mesencephalic veins. A second TVE resulted in complete obliteration of the
      fistula. In conclusion, detailed analysis of drainage routes is necessary for
      planning of treatment of patients with dural AVF, and prompt treatment is needed
      when redistribution of drainage routes develops during or after TVE.

PMID- 20678394
TI  - Classification of the venous route of carotid cavernous sinus fistula.
AB  - SUMMARY: It is important to investigate the venous routes in and around the
      carotid cavernous sinus before endovascular interventional treatment to avoid
      complications such as glaucoma and central retinal vein thrombosis. This paper
      classifies the anatomical features of the cavernous sinus and its venous routes
      and discusses four successfully treated cases.

PMID- 20678395
TI  - Transvenous Embolizations of Venous Compartments of Dural Arteriovenous Fistulas
      within Venous Sinus Walls.
AB  - SUMMARY: Transvenous embolization of venous compartments within the venous sinus
      wall was the method initially attempted for closing dural arteriovenous fistulas
      in 15 patients (22 sinuses). The venous channel, separate from the sinus lumen
      and located in the venous sinus wall, could be embolized in 6 lesions (3
      patients), including 3 superior sagittal sinus fistulas, 2 transverse sinus
      fistulas, and 1 straight sinus fistula. This technique resulted in closure of the
      fistulas and preservation of sinus patency as well as immediate improvement of
      clinical symptoms. The embolizable venous compartment of the fistula within the
      venous sinus wall could be detected by preoperative angiography, magnetic
      resonance imaging, and intraoperative venography. This unique drainage of dural
      arteriovenous fistulas may develop concurrently with more obvious portions of the
      fistula. Transvenous embolization of these venous compartments can close the
      fistulas and normalize impaired sinus function.

PMID- 20678396
TI  - The evaluation of preoperative embolization of meningioma.
AB  - SUMMARY: To evaluate the efficacy of preoperative embolization of meningioma, we
      examined the correlation between the angiographic disappearance of the tumor
      blush after the embolization and the volume of blood loss and transfusion
      intraoperatively. Preoperative embolization of meningioma with intravascular
      neurosurgery was attempted for 42 trials, 41 cases from July 1989 to December
      1995. There were no major complications attributed to the embolization procedure.
      As a subjective assessment in 23 cases the information from the surgeon following
      the operation was obtained. The angiographic disappearance of the tumor blush and
      reducing of the bleeding from tumor could be considered to be statiscally
      significant (p < 0.05). As an objective assessment in 37 cases following
      operation, the volume of both intraoperative blood loss and blood transfusion was
      examined. The angiographic disappearance of the tumor blush and reduced
      intraoperative blood transfusion could be also considered to be statiscally
      significant (p < 0.05), otherwise reduced intraoperative blood loss failed to
      reach the significance level. 1n this study the efficacy of preoperative
      embolization of meningioma has been especially shown to reduce intraoperative
      blood transfusion significantly, therefore it is very useful to increase the
      chance of complete tumor removal with more safely and less invasively.

PMID- 20678397
TI  - Fundamentals of transarterial embolization technique by drug-delivery embolic
      emulsion.
AB  - SUMMARY: We developed new embolic drug delivery emulsions to be utilized for
      malignant neoplasms. We combined additional water-soluble contrast materials
      (Ioxaglic acid, Iopamidol) with Glyceol, Poloxamer-188, or D-Mannitol to
      antitumor agent Lipiodol ultrafluid in order to generate stable emulsions. Some
      of these emulsions have been shown to cause pulmonary embolism in rabbits and to
      allow gradual diffusion of the antitumor agent in vitro. Good therapeutic utility
      is indicated. In particular, one emulsion containing D-Mannitol (Mizonokuchi
      emulsion), is expected to prolong drug delivery in malignant brain tumors.

PMID- 20678398
TI  - IDC Embolization of Aneurysms.
AB  - SUMMARY: Embolization using IDC was carried out for 33 aneurysm cases in the last
      3 years. The indication for the embolization was that the direct surgery was
      considered to be difficult, because of 1) technically impossible to do clipping,
      2) aneurysm of the posterior fossa, 3) reject of patients. Regarding the location
      of aneurysm, 27 cases were seen in the anterior circulation, and 6 cases in the
      posterior circulation. Count of 33 cases, 11 cases were ruptured and 22 cases
      were non-ruptured. The procedure of embolization of aneurysms are generalized as
      compared to direct surgery, but there remain some technical problems. 33 cases in
      our series had no significant complication, except for one which had ruptured
      again. We emphasize that the weak point of IDC which was so hard, had no
      variations, especially if it happens to migrate during locking procedure. These
      complications can be prevented, if we use GDC(5,6,7) instead of IDC.

PMID- 20678399
TI  - Intra-aneurysmal Occlusion of Cerebral Aneurysms Using Detachable Coils.
      Correlation of Aneurysm Neck Size and Treatment Results.
AB  - SUMMARY: The aneurysmal neck size seems to be an important factor in the
      endovascular treatment outcome(4,5). The purpose of the present study was to
      measure aneurysm neck size on angiographic films, and compare the measured value
      with the extent of intra-aneurysmal occlusion performed with detachable coils.
      The subjects were 22 patients with intracranial aneurysms treated using
      detachable coils. The cases were divided into two groups according to the
      aneurysmal neck size, 4 mm being the discriminating value for small neck. The
      neck of the aneurysm was successfully occluded in 19 of 22 patients. Ten
      aneurysms had a small neck and 9 aneurysms had a wide neck. Complete aneurysm
      occlusion was observed in 70% of small neck aneurysms and 25% of wide neck
      aneurysms. The results support that the size of the aneurysm neck correlates well
      with the effectiveness of endovascular treatment.

PMID- 20678400
TI  - Long-term results of ruptured cerebral aneurysms embolized in acute stage with
      interlocking detachable coils.
AB  - SUMMARY: We report on a series of eight patients presenting with SAH secondary to
      ruptured saccular (n=7) or dissecting (n=l) aneurysm, treated in the acute stage
      (within 14 days) by embolization with interlocking detachable coils (IDCs) who
      survived at least 3 months following initial hemorrhage. Embolization resulted in
      complete occlusion in 2 of 7 cases of saccular aneurysm, 90-95% occlusion was
      obtained in the remaining 5 cases of saccular aneurysm. Proximal occlusion with
      intra-aneurysmal coil packing was achieved in 1 case of dissecting aneurysm. In
      all 5 cases with partial occlusion, follow-up angiograms taken 2-4 months after
      the embolization showed partial recanalization due to coil compaction, while no
      recanalization was recognized in cases with complete occlusion in follow-up
      angiograms at 5 and 9 months respectively. Clinical disability, at 9 months after
      the embolization was rated as none in 4 cases, moderate in 1, and severe in 1.
      Two patients died of re-rupture at 4 and 8 months respectively after the
      embolization. Of the other 3 cases with partial recanalization, 2 were retreated
      by re-embolization or surgical clipping, one has been followed clinically and
      angiographically. Histological findings of the re-ruptured aneurysm showed
      neither endothelialization of the aneurysmal orifice nor organization of the clot
      around the coils. Aneurysmal re-rupture secondary to coil compaction related
      recanalization remains a critical factor in long-term clinical outcome and
      prognosis.

PMID- 20678401
TI  - Problems in endovascular procedures in acute ruptured intracranial aneurysms.
AB  - SUMMARY: Fifteen patients with acute ruptured intracranial aneurysms were treated
      with interlocking detachable coil (IDC) embolization. All graded poorly, i.e.,
      Hunt & Kosnik grades IV and V. Aneurysm occurred in the anterior circulation in
      14 patients and at the basilar tip in one, of these, 13 were small and 2 large.
      The endovascular procedure was conducted in a transfemoral approach under local
      anesthesia. Aneurysmal obliteration was examined transitionally after
      embolization. Final outcome was evaluated using the Glasgow outcome scale (GOS).
      Total aneurysmal occlusion was observed immediately after IDC embolization in 11
      patients. Two cases of coil migration to the parent artery occurred during
      endovascular procedure in patients with severe atherosclerosis. Aneurysmal
      rupture occurred during the endovascular procedure in a small internal carotid
      artery aneurysm when coil detachment failed. Follow-up angiography showed coil
      compaction in 2 patients, one patient experienced deterioration when the aneurysm
      ruptured. Eleven patients (73.3%) retained total aneurysmal occlusion and had no
      rebleeding. The overall GOS indicated good recovery in 5 patients, severe
      disability in 2, persistent vegetative state in 2, and death in 6. IDC
      embolization in severe acute ruptured intracranial aneurysm successfully
      prevented rebleeding, but our series was limited by the very small aneurysm size
      and the presence of severe atherosclerosis.

PMID- 20678402
TI  - Intracranial Aneurysm Embolization Using Interlocking Detachable Coils.
      Correlation between Volume Embolization Rate and Coil Compaction.
AB  - SUMMARY: The relationship between volume embolization ratio . and coil compaction
      on the intracranial aneurysm occluded using interlocking detachable coils (IDCs)
      was determined. From February 1994 to October 1996, 7 intracranial aneurysms were
      embolized using IDCs. Aneurysm capacity (volume) was calculated assuming that
      aneurysms are ellipsoid of the diameter in 3 planes. Coil volume was calculated
      assuming that IDCs are cylinders of primary coil. Coil compaction was observed in
      aneurysms embolized at a volume embolization ratio under 25%. There was no coil
      compaction in aneurysms embolized at a volume embolization ratio of over 25%.
      Measurement of the volume embolization ratio is useful to predict coil
      compaction. Intracranial aneurysms should be embolized at a volume embolization
      ratio of 25-33%.

PMID- 20678403
TI  - Endovascular stenting for pseudoaneurysms of the cervical carotid artery.
AB  - SUMMARY: The authors report two cases of pseudoaneurysm of the cervical carotid
      artery treated with endovascular stenting. One patient presented with cerebral
      ischemia due to traumatic carotid dissection and underwent stent placement 3
      weeks after injury when the wide-necked pseudo aneurysm was seen to enlarge at
      the dissecting portion. The aneurysm thrombosed while the carotid artery remained
      patent without ischemic complications for 2 years. The other patient developed
      repeated massive bleeding from an exposed pseudoaneurysm at the right carotid
      subclavian junction resulting from radiotherapy for thyroid cancer with
      subsequent skin infection. Since skin grafting failed and two attempts at coil
      embolization resulted in compaction with recurrent enlargement of the aneurysm,
      endovascular stenting was performed with endosaccular coil packing between the
      stent struts. Hemostasis was achieved for 2 months. Both cases illustrate
      successes of the stent in highly difficult situations.

PMID- 20678404
TI  - Tortuosity of the Cervical Segment of the Internal Carotid Artery in AVM
      Patients.
AB  - SUMMARY: The correlation between the degree of tortuosity of the cervical segment
      of the internal carotid artery (CICA) and the size of the nidus in AVM patients
      was investigated on angiograms. Fifteen AVM patients underwent embolization of
      vessels that were fed primarily by the internal carotid artery. The patients were
      divided into two groups according to the size of nidus: in group 1 (n=5), the
      size of the nidus was rated as small (less than 6 cm), in group 2 (n=10) as large
      (greater than 6 cm). The tortuosity was rated as mild, moderate, or severe. The
      tortuosity of the ipsilateral CICA in group 1 was severe while in group 2 it was
      either mild or moderate. The tortuosity of the CICA seems to be an important
      factor to be considered when distal embolization is contemplated in AVM patients.

PMID- 20678405
TI  - Results of 55 AVM Cases Treated by Embolization and/or Surgery.
AB  - SUMMARY: In order to build a data base for future comparison, we summarized the
      treatment results of cerebral arteriovenous malformation (AVM) patients in our
      hospital. Fifty five AVM patients who had been treated at Nagoya University
      Hospital from 1988 to 1995 were enrolled in the study. The patient
      characteristics were nearly the same as other reported series. Trend of treatment
      modality was changing in this period and embolization was increasing in its role.
      Karnofsky score was used to follow the patients' clinical status. It was useful
      to assess pretreatment clinical status and post treatment status. The results
      showed the improvement of the embolization procedure.

PMID- 20678406
TI  - 3D CT Angiography as a Pre-embolization Study for Embolization of Cerebral
      Aneurysms.
AB  - SUMMARY: An image guide for aneurysm embolization based on three dimensional CT
      angiography is reported. Multiplanner reformation (MPR) can measure the neck and
      dome of the aneurysm accurately enough to select the first coils for aneurysms.
      For neck evaluation, cut model and virtual endoscope are helpful because we can
      observe the neck from inside of dome or parent artery. Proximal arteries are
      visualized by 3D images and MPR if needed. Using laser lithography, we can get a
      real model of aneurysm and parent artery through which we can insert
      microcatheters and coils. 3D CTA is a dependable modality for embolization of
      cerebral aneurysms.

PMID- 20678407
TI  - Intravascular neurosurgery for cerebral aneurysm using interlocking detachable
      coils.
AB  - SUMMARY: Instead of the Guglielmi detachable coil (GDC; Target Therapeutics,
      Fremont, California), the interlocking detachable coil (IDC; Target Therapeutics,
      Fremont, California) was the only available detachable and retractable coil in
      Japan until February 1997. From October 1993 to February 1997, endovascular
      treatment with IDCs were attempted for 25 cases of cerebral aneurysm. Within 25
      trials, 15 cases were treated by intraaneurysmal coil embolization, 9 cases by
      parent artery or proximal occlusion using IDCs and one case could not be treated
      due to anatomical problems of the aneurysm. As for 15 cases of intraaneurysmal
      coil packing, complete occlusion was performed in 9 cases, subtotal occlusion in
      4 cases and partial occlusion in 2 cases. In one of the partial occluded cases, a
      coil compaction occurred 6 months after embolization. Distal emboli were
      recognized on CT after embolization in 3 cases, however, only one case was
      symptomatic. Intraoperative bleeding occurred in one case, but no obvious
      hemorrhage after coil embolization in any case. From our experiences, treatment
      for poor-grade ruptured aneurysm is still difficult, but intravascular surgery
      for cerebral aneurysms using IDC is possible and a useful alternative, especially
      for surgically difficult aneurysm.

PMID- 20678408
TI  - Matters to be Attended to in Intra-Aneurysmal GDC Embolization for Aneurysms with
      no Hemorrhage or Hemorrhage in Chronic Stage.
AB  - SUMMARY: Sixty-two aneurysms with no hemorrhage or hemorrhage in chronic stage
      were treated by intraaneurysmal GDC embolization in 69 sessions. The
      embolizations were performed under local anesthesia, systemic heparinization, 6F
      introducing catheter and double-markered microcatheter. Systemic heparinization
      was performed during the procedure and continued 48 hours afterwards except for
      the first 4 sessions in which only during the procedure. Activating clotting time
      (ACT) was maintained 2 to 2.5 times as long as base line value. Angiographic
      results were complete in 30, neck remnant in 27, and body filling in 12.
      Symptomatic embolism distal to the aneurysm were observed in two cases out of the
      first 4 cases without post-embolization heparinization. In the last 65 sessions,
      persistent symptomatic complications were observed in 4 patients, parent artery
      occlusion in 1 and embolism distal to the aneurysm in 3. Asymptomatic or
      transient complication was observed in 7 cases (parent artery occlusion or
      stenosis). Complications related to systemic heparinization were observed in 5
      cases. Difficulty of complete neck closure and recanalization of aneurysmal
      cavity mainly due to coil compaction are two main problems on GDC embolization.
      To avoid these two problems, it is be extremely important for GDC embolization to
      embolize the aneurysmal cavity as tightly as possible. On the other hand, the
      more tightly the aneurysmal cavity is embolized, the more frequently
      thromboembolic complications occur. Thus, systemic heparinization after the
      embolization is essential. However, one should been in mind that systemic
      heparinization itself carries a potential risk of hemorrhage. To overcome this
      dilemma, we use a special device for immediate and complete closure of the
      puncture site of the introducing sheath.

PMID- 20678409
TI  - Ion Implantation Modifies the Surface of GDCs. An Experimental Study in Swine
      Aneurysms.
AB  - SUMMARY: Ion implantation and protein-coatings were utilized to alter the surface
      properties (endothelial cellular adhesion) and enhance the thrombogenicity of
      Guglielmi detachable coils (GDCs) for endovascular treatment of cerebral
      aneurysms. These modified GDCs were compared with standard GDCs in the treatment
      of experimental swine aneurysms. Standard GDCs and ion-implanted protein coated
      GDCs were used to treat 32 aneurysms in 16 swine. GDCs were coated with either
      proteins, collagen (n=5), vitronectin (n=4), fibrinogen (Fn=3), laminin (n=2), or
      fibronectin (n=2) and underwent Ne(+) or He(+) implantation with a fluence of 1 x
      10(14--) 10(15) ions/cm(2) at an energy of 150 keV. Bilateral experimental swine
      aneurysms were embolized with standard GDCs (n=16) on one side and with ion
      implanted proteincoated GDCs (n=16; total) on the other side. The necks of
      aneurysms were evaluated macroscopically and histopathologically at autopsy using
      day 14 posttreatment specimens. Greater fibrous coverage of the necks of
      aneurysms were observed in the ion-implanted coil group. The results of this
      experimental study indicate that Ion implantation combined with protein coating
      of GDCs improved cellular adhesion and proliferation. Future application of this
      technology may provide early wound healing at the necks of embolized widenecked
      cerebral aneurysms.

PMID- 20678410
TI  - Results and problems on direct embolization of cerebral aneurysms using
      interlocking detachable coils.
AB  - SUMMARY: The clinical results of direct embolization of cerebral aneurysms using
      interlocking detachable coils (IDCs) were analysed. In 27 patients who underwent
      direct embolization of the aneurysm, 19 patients (70%) were treated uneventfully.
      In the other 8 patients, symptomatic or asymptomatic complications occurred;
      parent artery occlusion in 3 patients, rupture of the aneurysm in 2 patients,
      distal embolism in 2 patients, and neurological deterioration due to enlargement
      of the aneurysm after embolization in 1 patient. In 5 of 8 patients in whom
      complications occurred, neurological deficits disappeared after additional
      embolizations or thrombolysis therapies. Permanent deficits were observed in 3 of
      all patients (11%). These deficits were caused by the parent artery occlusion due
      to protrusion of the detached coil in wide neck aneurysms. These results suggest
      that indication of direct embolization of the cerebral aneurysm should be decided
      according to neck size. Balloon-assisted coil placement in wide-necked aneurysms
      was useful but unable to prevent protrusion or migration of the coils after
      balloon withdrawal. Development of a new device, such as a stent for intracranial
      use, may make it possible.

PMID- 20678411
TI  - Clinical results and complications of endovascular treatment for intracranial
      aneurysms.
AB  - SUMMARY: Thirty-two patients with intracranial aneurysm were treated via the
      endovascular approach and clinical results and complications were accessed. The
      aneurysms were on the anterior circulation, posterior circulation and feeding
      artery of AVM in 17, 12 and three patients respectively. In 17 (anterior
      circulation aneurysm), 12 patients underwent parent artery occlusion. There were
      two complications: cerebral embolism due to premature detachment of balloons and
      cerebral infarct due to parent artery occlusion. In 12 (posterior circuration
      aneurysm), four patients had complications: three infarcts due to parent artery
      occlusion and one aneurysmal bleeding at the interventional procedure. Coil
      compactions occurred in four cases. There were no complications in cases
      associated with AVM. Use of detachable balloons for intra-aneurysmal occlusion
      and intra-aneurysmal embolisation for partially thrombosed giant aneurysm tends
      to result in ischemic lesions where patient outcome is poor. We must pay
      attention to avoid these complications even though intra-aneurysmal embolisation
      using microcoils is currently performed safely.

PMID- 20678412
TI  - Endovascular Approach vs Microsurgical Approach for Posterior Circulation
      Aneurysms.
AB  - SUMMARY: We compare the results of detachable coil embolization with those of
      surgical clipping in patients with posterior circulation aneurysms. Surgical
      procedure was performed in 31 patients (basilar tip: 13 cases, SCA: 8 cases,
      basilar trunk: 1 case, VA: 9 cases). Thirty one aneurysms were treated by
      embolization with Guglielmi detachable coil (GDC) and interlocking detachable
      coil (IDC) (basilar tip: 14 cases, SCA: 1 case, basilar trunk: 6 cases, VA: 10
      cases). In surgical cases, clinical outcome at discharge showed good recovery
      (GR) in 14 cases, moderate deficits (MD) in 11 cases, severe deficits (SD) in 2
      cases, and dead (D) in 4 cases. In embolization cases, clinical outcome at
      discharge showed GR in 19 cases, MD in 4 cases, SD in 1 case, and D in 1 case.
      Embolization with detachable coils is less invasive than surgical clipping in the
      management of patients with posterior circulation aneurysms. Embolization with
      detachable coils in ruptured posterior circulation aneurysm cases at an early
      stage of SAH may improve clinical outcome.

PMID- 20678413
TI  - Usefulness of MRA in the Treatment of Dural AVM.
AB  - SUMMARY: We report 5 cases of dural AVMs, in which MRA images were considered
      very useful for evaluating the effectiveness of treatments, such as transvenous
      embolization therapy. MRA by time of flight method (TOF) with contrast medium for
      dural AVMs involving the cavernous sinus (dural CCFs) is necessary to assess the
      caliber of superior ophthalmic veins (SOVs) prior to treatment as well as
      immediately after treatment and during follow-up. MRA for dural AVM at the
      transverse-sigmoid sinus is useful for verifying thrombosed sinus in the dural
      AVM prior to transvenous embolization therapy and necessary to determine the
      approach to the nidus of the dural AVM(2).

PMID- 20678414
TI  - Percutaneous Transluminal Angioplasty for Bilateral ICA Occlusive Lesions.
AB  - SUMMARY: We performed Percutaneous Transluminal Angioplasty (PTA) in 50 patients
      with internal carotid artery (ICA) stenosis. Fifteen of these patients also
      showed signs of contralateral ICA occlusive lesions. Various neurological
      symptoms, such as hemiparesis or convulsions, frequently appeared in these
      patients with contralateral lesions during PTA. The balloon inflation time was
      restricted in 2 patients who experienced convulsions during PTA, resulting in an
      unsuccessful dilatation in one case. No permanent neurological deficits appeared
      as a result of PTA in these cases. The treatment for these cases is discussed in
      this report.

PMID- 20678415
TI  - 2D-TOF MRA Follow-up Study of Percutaneous Transluminal Angioplasty for Severely
      Stenotic Cervical Internal Carotid Artery.
AB  - SUMMARY: Percutaneous transluminal angioplasty (PTA) for severe arteriosclerotic
      stenosis in the cervical internal carotid artery (ICA) was successfully carried
      out in 23 cases between December 1994 and August 1996. In order to analyze the
      condition of the cervical ICA in the early stage after PTA, 12 stenotic lesions
      of 11 cases were exposed to follow-up study of stenotic cervical ICA after PTA
      with magnetic resonance angiography (MRA) 1 to 150 days postoperatively. In six
      lesions, the diameter of the cervical ICA was dilated sequentially. In another
      four lesions, the diameter of the cervical ICA was decreased in the first three
      weeks and dilated over the next three weeks. Angiographically, these lesions had
      a small intimal flap at the balloon dilated portion, which was speculated to
      cause the turbulent flow in the first stage. In the remaining 2 lesions,
      restenotic changes in cervical ICAs were observed within three weeks after PTA.
      Follow-up angiography was performed over three months after PTA in five cases of
      this series and compared with MRA. Consequently, the diameters of the cervical
      ICA between angiography and MRA were closely correlated. The evaluation of the
      lesion after PTA of the cervical ICA demonstrated that MRA is beneficial, but
      within three weeks after PTA, caution should be paid for underestimation of the
      small intimal flap on MRA.

PMID- 20678416
TI  - Percutaneous transluminal angioplasty for acute thrombotic occlusion of the
      cervical internal carotid artery using a perfusion balloon catheter.
AB  - SUMMARY: We performed emergency percutaneous transluminal angioplasty (PTA) with
      a perfusion balloon catheter (PBC) for PTCA and, at the same time, thrombolytic
      therapy was administered by urokinase (UK) perfusion in five cases of severe
      cervical internal carotid artery stenosis in which sudden cerebral hemisphere
      ischemia occurred due to acute thrombotic obliteration. In four out of the five
      cases, effective revascularization was obtained; three resulted in Good recovery,
      but one showed extensive cerebral infarction after PTA. In the remaining one
      case, where stenosis of the internal carotid artery of the opposite side occurred
      subclinically, effective revascularization by PTA was impossible resulting in the
      death of this patient. While "artery to aetery embolism" was confirmed in all
      four cases in which revascularization was successful, most emboli were dissolved
      by combined thrombolysis. As poor prognostic factors, findings of a low density
      area and closing of cerebral sulci in an initial CT and poor development of the
      collateral circulation mediating the circle of Willis and leptomeningeal
      collateral on the cerebral surface were indicated. Since PBC is capable of
      performing PTA while assuring circulation distant from the balloon, it
      facilitates gradual and prolonged balloon inflation, which is said to be safer
      and more effective, and is considered a reasonable method of revascularization at
      the time of an acute obliteration in the cervical internal carotid artery. In
      addition, this method can be used as a bridge to carotid endarterectomy. However,
      "artery to artery embolism" accompanying PTA in the acute stage remains a major
      problem, and a combination of thrombolysis seems indispensable.

PMID- 20678417
TI  - Detection of Embolic Signals during and after Percutaneous Transluminal
      Angioplasty of Subclavian and Vertebral Arteries Using Transcranial Doppler
      Ultrasonography.
AB  - SUMMARY: We investigate the safety and/or risk of PTA for vertebral and
      subclavian artery stenosis by monitoring embolic signals using transcranial
      Doppler (TCD) ultrasonography. Twelve consecutive patients undergoing PTA for
      subclavian and vertebral artery stenosis of atherosclerotic origin were studied.
      Before, during and after PTA, TCD monitoring was performed to detect embolic
      signals for 30 minutes at each time. No embolic signals were detected in any
      patient before angioplasty. During angioplasty, one embolic signal was detected
      immediately after balloon deflation in one of 12 patients. Several embolic
      signals were detected after the procedure in six of 12 patients, but thereafter
      embolic signals became less frequent in number. Three days after angioplasty,
      embolic signals were not detected in any patient. TCD monitoring could be a
      useful modality for detection of microemboli during and after PTA in the
      posterior circulation. Our present study suspected that subclinical micro emboli
      are released from the dilated vessels for three days after vertebral and
      subclavian PTA and anticoagulant or antiplatelet therapies may prevent embolic
      complications after the procedure.

PMID- 20678418
TI  - Successful Treatment of Superior Sagittal Sinus Thrombosis. Direct Thrombolysis
      with Local Infusion of t-PA via Venography in the Acute Phase.
AB  - SUMMARY: A 22-year-old pregnant women showed a rapid deterioration in her
      clinical condition. Superior sagittal sinus thrombosis was diagnosed, and direct
      transvenous infusion of t-PA into the superior sagittal sinus was performed. This
      treatment resulted in recanalization of the occluded superior sagittal sinus and
      in a dramatic improvement of neurological deficits.

PMID- 20678419
TI  - Transarterial embolization of cerebrospinal lesions with liquid coils.
AB  - SUMMARY: We report our experience with endovascular embolization using liquid
      coils. Twenty-two transarterial embolization procedures were performed with these
      coils in 20 patients with cerebrospinal vascular or neoplastic lesions. The coils
      were delivered into the target vessels under fluoroscopic monitoring through a
      microcatheter by manual injection and flushing with saline. Subsequent surgical
      resections of embolized lesions were performed in 14 cases, and radiosurgery for
      two. Complete obliteration of the target vessels were accomplished in all cases
      without complications. Passage through the microcatheter and delivery of the coil
      was smooth. Proximal protrusion of the coil occurred during the procedure, and a
      combination of other embolic materials was necessary to completely occlude large
      vessels in 9 cases. The embolized lesions were easily resected in the following
      neurosurgery. Liquid coils were safe and effective as an embolic material in use
      prior to surgery or radiosurgery.

PMID- 20678420
TI  - Embolization of aneurysms with a liquid material. An experimental study.
AB  - SUMMARY: The authors evaluated the embolization effects on experimental aneurysm
      models with a liquid material. This material is a mixture of poly (HEMA-co-MMA),
      Iopamidol, water and a small amount of ethyl alcohol. We have satisfactorily
      treated over 30 cases of AVM with this material. Out of four solutions of
      different viscosity, we used the solution with the highest viscosity to prevent
      distal migration of the mixture. Glass models of aneurysms of 5 mm in diameter in
      pulsatile saline flow were embolized with the mixture under various conditions.
      When an IDC was placed in the aneurysm models, the mixture obliterated them
      completely and did not migrate out from the aneurysm models. In this experimental
      study, it is suggested that the liquid material appears to be useful in
      embolizing cerebral aneurysms safely.

PMID- 20678421
TI  - Endovascular Treatment for Tandem Internal Carotid Stenosis. Development of a New
      Shunt Tube for PTA.
AB  - SUMMARY: Three patients with tandem internal carotid stenoses were treated in one
      operation including carotid endarterectomy (CEA) for the proximal stenosis and
      percutaneous transluminal angioplasty (PTA) for the distal stenosis. We devised a
      Y-shaped shunt tube which we used for CEA, while a PTA balloon catheter was
      introduced via the tube to perform PTA guided by portable digital subtraction
      angiography (DSA). No cerebrovascular events occurred during follow-up. Our
      approach avoids the risk of a second procedure while effectively treating tandem
      stenoses.

PMID- 20678422
TI  - A microguide wire with a scale (scaler guide). Technical note.
AB  - SUMMARY: There are various methods for measuring an affected vascular size during
      embolization or percutaneous transluminal angioplasty (PTA). Metallic balls,
      electrodes, grids, coins on the skin were simple and useful in this sense, but
      not stable and exact for measuring. A 0.014" or 0.016" microguide wire with 5
      gold markers in the tip is newly developed and used clinically (a scaler guide).
      One marker measures 1 mm in length. There is a distance of 4 mm between two
      neighboring markers. A microcatheter is navigated using a standard microguide
      wire into the vessels of the lesion. Bilateral digital subtraction angiography
      (DSA) is performed after exchange of a microguide wire with a scaler guide.
      Magnification ratio between distance measured by DSA and real distance from
      markers is calculated. Thereafter, the size of the vessels will be measured. With
      this method, the size of vessels was measured in patients with aneurysm or
      arteriovenous malformation or stenotic lesion. Selection of coils or PTA balloons
      could be made easily and effectively. Interventions were more safely performed
      with this new scaler guide.

PMID- 20678423
TI  - Investigations of the Dose of Heparin and Whole Blood Coagulation Time during
      Endovascular Surgery.
AB  - SUMMARY: We chronologically determined whole blood coagulation time during
      continuous heparin administration, and investigated optimal doses of heparin in
      thirty-seven vascular surgery cases. ACT was determined with Hemochron 401.
      Heparin (2000 IU) was administered by bolus injection at the beginning of
      intravascular surgery, which was followed by continuous injection of 20 to 160
      IU/kg/h. ACT determined before and 30 minutes after heparin administration were
      compared. There were no complications. ACT was maintained at a nearly constant
      level by continuous heparin administration. The dose of heparin required to
      maintain ACT at a level 1.5 to 2 times the initial level was 20 to 60 IU/kg/h.
      ACT was prolonged by more than three times in two of the ten subjects who were
      given heparin at a dose of 70 IU/kg/h or more. Continuous administration of
      heparin allowed maintenance of ACT at a nearly constant level during
      intravascular surgery. ACT was maintained within the range which is believed to
      be effective for prevention of thrombus formation (approximately 1.5 to 2.0 times
      larger than the initial level) by continuous administration of 20 to 60 IU/kg/h
      of heparin. ACT was, however, prolonged to more than three times the initial
      level in some subjects who were given 70 IU/kg/h or higher doses, suggesting the
      risk of a bleeding tendency. Accordingly, it is ideal to continue heparin
      administration at appropriate doses, while measuring ACT. The results of our
      study should serve as a useful standard for meeting this goal.

PMID- 20678424
TI  - Interventional neuroradiology in Thailand: 1989-1997.
AB  - SUMMARY: In 1979 the Siriraj team in Bangkok began exploring a field that was
      then new in Thailand, i.e. interventional neuroradiology. This first phase
      consisted mostly in self-training and foreign exposure. It included experimental
      work with animal models, as well as early clinical trials designed to assess our
      skills in particle embolisation and the ligated and detachable balloon
      techniques. In 1990 a new phase started. Essential techniques were acquired in
      collaboration with the neurovascular unit of Bidtre Hospital in France during a
      three year training programme. Throughout this period, the support of the
      Association Medicale Franco-Asiatique (AMFA) and the French foreign affairs
      department proved vital. Our department progressively became a referral centre
      for the different techniques used in embolisation (balloons, glue...) and for
      various vascular lesions of the brain, the head and neck region, and spinal cord
      diseases. Within Mahidol University, the Ramathibodi and Prasat Hospital centres
      started the same interventional neuroradiology training program in 1995; they
      benefited from the same tutors and connections as Siriraj. In 1996, the newly
      acquired biplane DSA machines in both centres enabled us to improve the treatment
      of arteriovenous malformations - using the glue technique -, intracranial
      aneurysm - using GDC-coils-, clot lysis, angioplasty...ete. According to
      international recommendations, the critical mass we reached in 1997 in terms of
      number of patients and interventions, allows us to offer training in endovascular
      techniques to junior neuroradiologists at Mahidol university.

PMID- 20678425
TI  - How to avoid bias: methodological vigilance.
AB  - SUMMARY: One of the main purposes of choosing and developing a strategy for
      clinical research is to attempt to reduce bias. The avoidance of bias is build on
      methodological vigilance: The researcher should be familiar with the most common
      sources of bias. This vigilance is supported by guidelines and the development of
      methodological standards. Where sources of bias cannot be eliminated it is
      important to identify them so that they may 'be considered when conclusions are
      drawn from a study. Randomized controlled trials (RCT) have the greatest
      potential to reduce bias, but conducted without methodological vigilance the
      trial's guarantee of lack of bias is lost. Methodological vigilance has also to
      be applied when results of different RCT's are combined and used for clinical or
      research purposes.

PMID- 20678426
TI  - Endovascular management of paediatric intracranial aneurysms.
AB  - SUMMARY: The purpose of this paper is to discuss the radiological and clinical
      features of paediatric intracranial aneurysms including endovascular techniques
      currently being used for their therapy. Paediatric patients who presented with
      the diagnosis of intracranial aneurysm between August 1982 and February 1997 were
      included. The data were collected retrospectively. Clinical features included
      patient's age, sex, presentation, treatment and outcome. Radiologic features
      included location, size and number of aneurysms present. 21 patients (13 females
      and 8 males) ranging in age from 9 months to 16 years had intracranial aneurysms.
      Seventy six percent of the aneurysms were located in the anterior circulation and
      24% in the posterior circulation. Seven patients (33%) had giant aneurysms and
      three patients (14%) had multiple aneurysms. Endovascular treatment was performed
      in six patients (29%) and neurosurgical treatment in eight patients (38%).
      Endovascular treatment included the use of coils and/or balloon occlusion. Of the
      remaining patients, two (9.5%) died prior to any surgical or radiological
      intervention. A further five patients (24%) were treated conservatively.
      Intracranial aneurysms in children demonstrate clinical and radiologic features
      that differ significantly from those seen in adults. There is a higher percentage
      of ICA termination aneurysms, giant aneurysms and posttraumatic aneurysms.
      However, aneurysms in children, like those in adults, can and have been
      successfully treated utilizing endovascular as well as neurosurgical techniques.

PMID- 20678427
TI  - Aneurysmal disease in children. Review of 20 cases with intracranial arterial
      localisations.
AB  - SUMMARY: Twenty children (13 males, 7 females), referred to our group with non
      traumatic intracranial aneurysms between 1978 and January 1997, were included in
      this study. Their angiograms were reviewed to assess number, location, type of
      aneurysms and evolution before and after treatment. Their ages ranged from 1
      month to 15 years. Seven patients (35%) presented with subarachnoid haemorrhage
      (SAH). Eleven patients (55%) presented with focal neurological deficits or
      seizures: epileptic seizures occurred in five patients, neurologic deficits or
      focal symptoms due to mass effect occurred in six. Total number of diagnosed
      intracranial aneurysms was 24. The most common sites involved were internal
      carotid (37%) and vertebrobasilar (32%) systems. The aetiology of the aneurysms
      was infective in four patients and unknown in the remaining 16 patients (80%).
      Endovascular treatment was successful in seven patients (37%). Three patients
      (15%) were surgically treated. Seven patients (35%) were conservatively treated.
      Two patients (10%) had spontaneous thrombosis of the aneurysm. SAH was more
      frequent in males, and never occurred in children under five years old. Frequent
      presentations such as focal symptoms or mass effect and less prevalence of
      aneurysm rupture are probably due to the high prevalence of large or giant
      aneurysms (25%) in our series. In conclusion, radiological findings and the
      natural history of symptomatic arterial aneurysms in children are clearly
      different from those in adults. Probably pathogenetic factors and aetiology are
      also different. Shear stresses, haemodynamic and hormonal factors do not appear
      to be dominant to reveal such defects, though their correction favours repair.
      Since repair is frequent, conservative treatment has a major role in their
      aneurysm management.

PMID- 20678428
TI  - Otorrhagia from the "aberrant internal carotid" artery in the middle ear.
      Surgical and endovascular aspects.
AB  - SUMMARY: Agenesis of the cervical portion of the internal carotid artery (ICA)
      may result in blood supply to the ipsilateral cerebral hemisphere being provided
      by an enlarged inferior tympanic branch of the ascending pharyngeal artery. This
      enlarged vessel, passing through Jacobson's canal and anastomosing with the
      likewise enlarged caroticotympanic branch of the ICA in front of the
      promontorium, may simulate a middle ear mass. We present five patients with this
      unusual anatomical variant, three of which underwent biopsy of what was believed
      to be a middle ear tumour. One patient experienced rupture of an arterial
      aneurysm in the middle ear successfully treated with endovascular application of
      detachable platinum coils. It is mandatory for ENT-surgeons and radiologists who
      perform head-and-neck examinations to recognize this anatomical variant, not
      mistaking it for a tumour, since biopsy of a large artery supplying the brain may
      have disastrous consequences. In patients with otorrhagia, an arterial aneurysm
      must be considered as a possible source of bleeding, in some cases amenable for
      treatment with an endovascular technique. The diagnosis of "aberrant internal
      carotid artery"" is usually made with CT of the temporal bone or MR of the skull
      base. Cerebral angiography is in most cases not necessary, unless an endovascular
      procedure is planned.

PMID- 20678429
TI  - Embolisation of branches of the ophthalmic artery.
AB  - SUMMARY: Nine patients presenting various orbital and skull base pathologies
      embolised through the ophthalmic artery are reported. All cases were catheterised
      beyond the bend around the optic nerve (second portion of the intraorbital
      ophthalmic artery). Embolisation was carried in all with n-butyl cyano-acrylate
      without post interventional visual disturbance. Relying on the classic
      description as well as previous personal work on the ophthalmic artery anatomy
      and angiographic anatomy, all procedures were performed under general anaesthesia
      without functional testing. The central retinal artery and the long ciliary
      arteries arise from the first or second portion of the ophthalmic artery. For
      embryological reasons no branch to the visual tract can arise from the ophthalmic
      trunk distal to the origin of the superficial recurrent meningeal artery or the
      lacrimal artery. Therefore distal catheterisation at least beyond the second
      portion, (and injection without reflux) makes safe embolisation possible in all
      variations of internal carotid origin of the ophthalmic stem. Independent from
      the expected goal of the embolisation, the use of particles in this territory
      should in our opinion be discouraged.

PMID- 20678431
TI  - The anterolateral transpetrosal approach to the clivus and the pons. Preoperative
      embolisation of the inferior petrosal sinus.
AB  - SUMMARY: Resection of skull base tumors is a real challenge in the field of
      neurosurgery. Anterior petrosectomy gives one of the best approaches to reach the
      clivus and the pons while avoiding cerebral retractions which are responsable for
      postoperative complications. Using a subtemporal extradural or an infratemporal
      preauricular route, the anterolateral transpetrosal approaches produce a
      resection of the anterior pyramidal bone around the petrous carotid artery. These
      approaches offer a direct view of the posterior fossa dura between the two
      petrosal sinuses, to give access to the petroclival area. However, exposure of
      the intradural structures in the foramen magnum area is always restricted because
      of the inferior petrosal sinus. Its peroperative hemostasis is always truly
      challenging on account of its size and encasement within a wide petrooccipital
      suture. The goal of the preoperative embolisation of the inferior petrosal sinus,
      whenever possible, is to allow its peroperative section without haemorrhage for a
      wider exposure along the lower clivus.

PMID- 20678430
TI  - Spinal cord arteriovenous fistula associated with a giant venous pouch in a three
      year-old child.
AB  - SUMMARY: An unusual case of direct spinal cord arteriovenous fistula (SCAVF)
      associated with a large venous pouch in a three-year-old child is presented.
      Features of this rare vascular lesion on MRI and selective angiography are
      described.

PMID- 20678432
TI  - [Antiviral treatment of special patients groups with hepatitis B virus
      infection].

PMID- 20678433
TI  - [The present situation and pondering on antiviral therapy in patients with
      decompensated cirrhosis].

PMID- 20678434
TI  - [Antiviral treatment for pregnant women with chronic HBV infection].

PMID- 20678435
TI  - [Anti-HBV strategies for post liver transplantation patients, chemotherapy and
      immunosuppressive agent user].

PMID- 20678436
TI  - [Treatment of hepatitis B co-infected with HCV or HIV].

PMID- 20678437
TI  - [Antiviral therapy in children hepatitis B patients].

PMID- 20678438
TI  - [Resistance mutation patterns of hepatitis B virus in patients with suboptimal
      response to adefovir dipivoxil therapy after lamivudine resistance].
AB  - OBJECTIVE: To investigate the resistance mutation patterns of hepatitis B
      virus(HBV) during adefovir dipivoxil (ADV) monotherapy or combination therapy
      after lamivudine(LAM) resistance. METHODS: Serum samples from fifteen patients
      with suboptimal viral response to ADV therapy after LAM resistance were
      collected. The RT region of HBV P gene was PCR-applied, cloned and sequenced, and
      the mutation patterns in relation to resistance were analyzed. RESULTS: The ADV
      resistance mutation patterns of A181T+N236T, A181V, A181T were selected in ADV
      monotherapy group. The LAM resistance mutation patterns of M204V+L180M,
      M204V+L180M+L229V, M204I+L80I, M204V+L180M+V207I were detected in the combination
      therapy group. 20% of clones from three serum samples were detected double
      resistance to LAM and entecavir (ETV) in the combination therapy group, the
      resistance patterns were M204I+L80I+T184I (2/10), M204V+L180M+T184S (2/10), and
      M204V+L180M+G173L+S202G (2/10) respectively. I269L clones were detected in two
      serum samples from both two groups and P109S clones also detected in the one from
      monotherapy group. CONCLUSIONS: In the patients with suboptimal viral response to
      ADV therapy after LAM resistance, the ADV resistance mutation patterns of
      A181T+N236T, A181V and A181T could easily be selected during ADV monotherapy;
      while in the patients with combination therapy, the LAM resistance mutation
      patterns of M204V+L180M, M204V+L180M+L229V, M204I+L80I, and M204V+L180M+V207I
      were predominant, the ETV resistance mutation T184I/S and S202G could be
      selected. The mutation patterns of I269L and P109S may impact the responses to
      ADV therapy in some patients.

PMID- 20678439
TI  - [Experimental studies of rAd-p53 injection by interventional approach for the
      treatment of rabbit VX2 liver cancer].
AB  - OBJECTIVES: To evaluate the efficacy of recombinant human adenovirus p53 gene
      therapy (rAd-p53) in the rabbit VX2 liver cancer model using different
      interventional therapy approach. METHODS: Thirty New Zealand rabbits implanted
      with VX2 tumor in the liver were randomized into five groups with six of each.
      The tumor volumes (V1) were measured by MRI and CT scan 11 days after tumors
      implanted. The interventional therapy scheme performed as below: intraarterial
      0.9% saline solution perfusion in group A, transcatheter arterial embolization
      with 0.5 ml ultrafluid lipiodol in group B, intraarterial rAd-p53 gene perfusion
      in group C (1 x 10(6)/VP); intraarterial rAd-p53 gene perfusion (1 x 10(6)/VP) in
      combination with transcatheter arterial embolization (ultrofluid lipiodol, 0.5
      ml) in group D and intratumoral rAd-p53 gene (1 x 10(6)/VP) injection in group E.
      The tumor volumes (V2) were measured by MRI and CT scan, and the tumor growth
      ratios were calculated 14 days after interventional procedures. Then all animals
      were sacrificed. RESULTS: The tumor tissues were explanted for
      immunohistochemistry to observe the expressions of vascular endothelial cell
      growth factor (VEGF) and factor VIII. Microvessel density (MVD) of the tumor
      tissues was assessed by factor VIII immunohistochemical analysis. In addition,
      apoptotic index was assessed by terminal deoxynucleotidyl transferase dUTP nick
      end labeling (TUNEL) staining. The tumor volumes before therapy were (79.4+/
      8.2), (75.3+/-7.8), (74.6+/-6.6), (78.7+/-9.1), (75.8+/-8.4) mm(3) respectively,
      without differences found among them (F = 12.248, P = 0.0636). But the tumor
      volumes after therapy were (564.7+/-96.7), (176.5+/-83.2), (239.6+/-42.8),
      (159.8+/-58.6), (334.7+/-32.6) mm(3) respectively (F = 24.537, P = 0.0218). The
      tumor growth ratios were 6.9, 2.6, 3.1, 1.6 and 4.1 respectively. The mean
      apoptosis index were 12.0%+/-1.1%, 14.5%+/-2.1%, 17.6%+/-2.3%, 18.6%+/-2.3% and
      19.6%+/-2.5% respectively. with significant differences in group E in comparison
      with the other four groups. Mean positive ratio of VEGF was 50.0%, 83.3%, 83.3%,
      50.0% and 50.0% respectively, with significant differences observed in group B
      and group C compared with the other three groups (F = 7.84, P = 0.019). The
      differences of VIII factor positive expression ratio among each group were
      significant (F = 0.854, P = 0.018). Statistical analysis showed a positive
      correlation between the expression of VEGF and MVD (r = 2.400, P = 0.0233).
      CONCLUSION: The rAd-p53 has effective treatment outcomes in VX2 rabbit liver
      cancer, and intra-arterial rAd-p53 gene perfusion in combination with
      transcatheter arterial embolization is the best approach in comparison with intra
      arterial rAd-p53 gene perfusion, transcatheter arterial embolization and
      intratumoral rAd-p53 gene injection alone.

PMID- 20678440
TI  - [Expression characteristics of hypoxia inducible factor-1a and its clinical
      values in hepatocellular carcinoma].
AB  - OBJECTIVE: To investigate the dynamic expression of hypoxia inducible factor
      1alpha (HIF-1alpha) and its clinical values in hepatocellular carcinoma (HCC).
      METHODS: The dynamic changes of liver pathology, HIF-1alpha transcription and
      expression were observed through the hepatoma model. The self-control specimens
      from 35 human HCC patients were collected and the expression, cellular
      distribution, and clinicopathological features of HIF-1alpha and its gene was
      analyzed by immunohistochemistry, western blotting and nested- PCR, respectively.
      RESULTS: Both levels of hepatic HIF-1alpha and HIF-1alpha mRNA expression
      increased during the HCC development course. The incidence of HIF-1alpha and the
      ratio of HIF-1alpha to beta-actin was 0% and 0.16+/-0.02 in the control rats,
      77.8% and 0.29+/-0.04 in the denatured rats, 88.9% and 0.52+/-0.03 in the
      precancerous rats, and 100% and 0.84+/-0.02 in the cancerous rats respectively,
      with significant difference between the control group and any of the experimental
      groups (P = 0.000). The positive HIF-1alpha was brown and granule-like and mainly
      presented in cytoplasm and few in nucleus. The incidence of HIF-1alpha was 80%
      (28/35) in HCC and 100% (35/35) in its surrounding tissues. The clinical
      pathological features indicated HIF-1alpha expression associated with tumor size
      and differentiation degree the of HCC. No correlation was found between HIF
      1alpha and tumor numbers or positive-HBsAg. CONCLUSIONS: HIF-1alpha expression is
      associated with occurrence and development of HCC, and is perhaps a target
      molecule for HCC therapy.

PMID- 20678441
TI  - [The association of hepatitis B virus genotype and the basal core promoter
      mutation in Qidong, China].
AB  - OBJECTIVES: To investigate the prevalence of hepatitis B virus (HBV) genotypes
      and the association with hepatocellular carcinoma (HCC) or basal core promoter
      (BCP) mutation in Qidong, China. METHODS: The whole genome of HBV or X gene
      sequences were obtained from serum samples of HBV infected patients by using PCR
      and direct sequencing methods. Phylogenetic tree was constructed to determine the
      genotypes or subgenotypes of HBV. RESULTS: According to the phylogenetic tree
      constructed from full-length sequence of HBV, genotype C2 was predominant in
      Qidong area. It was prevalent in 44 out of the 48 cases (91.7%), whereas genotype
      B2 only existed in 4 cases (8.3%). No other genotypes or recombinant types were
      found in Qidong patients. The result of genotyping based on X gene sequence
      confirmed the above observation. In a total of 182 samples, 169 (92.9%) showed
      genotype C2 and 10 (5.5%) showed genotype B2. There were 3 (1.6%) patients showed
      a coinfection with C2 and B2. The infection rate of genotype C in Qidong was
      significantly higher than that in neighboring city Shanghai (chi(2) = 12.252, P
      less than 0.01). There was no significant difference of genotype distribution
      between HCC and chronic hepatitis groups (P is more than 0.05). The frequency of
      T1762/A1764 double mutation in genotype C2 (70.3%) was significantly higher than
      that in genotype B2 (30.8%, P less than 0.05). The other two types of point
      mutation which also occurred in BCP, i.e. T1766 and A1768, were only seen in
      genotype C2. CONCLUSION: (1) Genotype C2 is the predominant genotype in Qidong,
      China. (2) There is no association between genotype C and HCC in Qidong. (3)
      Genotype C has a higher prevalence of BCP mutation than genotype B.

PMID- 20678442
TI  - [Increased coronin-1C expression is related to hepatocellular carcinoma invasion
      and metastasis].
AB  - OBJECTIVE: To search for hepatocellular carcinoma (HCC) invasion related
      biomarkers using the cell membrane proteomics approaches, and to validate the
      markers using experimental and clinical specimens. METHODS: The HCCLM9 and
      MHCC97L cells with a similar genetic background and remarkably different
      metastasis behaviors were used for comparative membrane proteome profiling using
      sodium dodecyl sulfate polyacrylamide gel electrophoresis and electrospray
      ionization mass spectrometry technologies. Candidate protein makers were further
      validated by western blot on cells, immunohistochemistry (IHC) on animal tumor
      tissues, and tissue micro-array on clinical specimens. RESULTS: The membrane
      proteins of MHCC97L and HCCLM9 cells were compared by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis analyses. 14 proteins were identified by ESI
      MS/MS among the differential bands. Coronin-1C was overexpressed in HCCLM9
      (7.31+/-0.73) versus MHCC97L (2.84+/-0.99) validated by western blot. Elevated
      coronin-1C expression was observed in liver cancer tissues of HCCLM9 nude mice.
      IHC study in 115 human HCC specimens demonstrated that patients with higher
      coronin-1C expression had more advanced stage. CONCLUSION: The study suggests
      that coronin-1C could be a potential molecule to predict HCC invasive behavior.

PMID- 20678443
TI  - [The clinical characteristics of hepatic failure with aspergillosis].
AB  - OBJECTIVES: To study the clinical characteristics of hepatic failure with
      aspergillosis. METHODS: The data of hepatic failure patients with fungal
      infection hospitalized in our hospital form January 1985 to June 2006 were
      collected. This research mainly focused on the clinical characteristics of the
      patients co-infected with aspergillosis. RESULTS: The occurrence of aspergillosis
      was 20.5% (104 cases) among 507 hepatic failure patients with fungal infection.
      Compared with other fungal infection in hepatic failure patients, the effective
      rate of antifungal therapy and the improvement rate of underlying disease were
      worse in patients with aspergillus infection (36.5% vs 57.8%, P = 0.000; 26.0% vs
      36.7%, P = 0.049). Aspergillus fumigatus was the most common species among 108
      fungal species. The species next to Aspergillus fumigatus were Aspergillus niger
      and Aspergillus flavus. The mainly infected organ was lung and its clinical
      manifestation was atypical. Liver function could be improved with effective anti
      fungus therapy. CONCLUSIONS: Diagnosis and treatment of aspergillosis is
      difficult in hepatic failure patients co-infected with aspergillosis. Early and
      effective antifungal therapy is helpful to the recovery of liver function in the
      hepatic failure patients suspected with aspergillosis co-infection.

PMID- 20678444
TI  - [Diagnosis and managements of seventeen patients with hepatic veno-occlusive
      disease].
AB  - OBJECTIVE: To summarize the clinical experiences in the diagnosis and managements
      of hepatic veno-occlusive disease (HVOD). METHODS: The clinical and pathologic
      data of 17 patients with hepatic veno-occlusive disease were analyzed
      retrospectively. RESULTS: According to the results of imaging examination,
      clinical data and pathological data, 17 patients HVOD were divided into acute
      progressive HVOD and chronic HVOD. 2 cases out of the 11 acute progressive cases
      got improved, 2 cases died after medical treatment and 2 cases died after shunt
      operation. The 6 chronic HVOD, including 1 case with medical treatment and 5
      cases with shunt operation, were cured. CONCLUSION: Liver biopsy was an efficient
      method for the diagnosis of hepatic veno-occlusive disease. Acute progressive
      cases of hepatic veno-occlusive disease should be managed with medical treatment
      and the chronic cases could be treated with shunt surgery if medical treatment
      were inefficient.

PMID- 20678445
TI  - [The role of miRNA-122 expression during the acute liver failure in mice induced
      by D-GalN/LPS].
AB  - OBJECTIVE: To investigate the expression of miR-122 and its relationship with
      progression and development of acute liver failure in mice induced by D-GalN/LPS,
      and to explore new biomarker(s) for early diagnosis of acute liver failure.
      METHODS: BALB/C mice were randomly divided into four groups: the mice were given
      D-GalN (900 mg/kg body weight) and LPS (10 micog/kg body weight)
      intraperitoneally (i.p.) to construct the acute liver model; whereas the control
      groups were given D-GalN (900 mg/kg), LPS (10 microg/kg) and normal saline
      respectively. All biochemical and histological indexes were determined at 0, 1,
      3, 5, 7 and 9 h respectively after administration. Real-time RT-PCR were used to
      detect the expression of miR-122 and pro-inflammatory cytokines, furthermore, the
      expression of miR-122 was verified by LNA (lock nucleic acid)-Northern-blot. ALT
      and AST levels were tested by biochemistry analyzer. Serum pro-inflammatory
      cytokine levels were tested by ELISA. RESULTS: The mortality rate was about 80%
      at 24h after D-GalN/LPS treatment, but no mortality was observed in the other
      three control groups. Liver special miRNA miR-122 was highly expressed in liver
      tissue of normal mice (ct is approximately equal to 14), it was up-regulated
      significantly (P = 0.013) at first hour after treatment then down-regulated
      according to the development of acute liver failure, the change was more obvious
      at 9 h (ct is approximately equal to 15, P = 0.002). ALT and AST levels increased
      obviously at 3h after treatment and reached peak at 7 hours then they were
      declined sharply. It was found that the expression of miR-122 was faster and more
      durable than ALT. Pro-inflammatory cytokines related to acute liver failure
      including TNFa and IL-6 were all up-regulated in serum as well as liver tissue (P
      less than 0.05). Correlation analysis showed that miR-122 had a negative
      correlation with ALT (correlation coefficients -0.505) and positive correlations
      with TNFa and IL-6 (correlation coefficients were 0.493 and 0.674 respectively).
      CONCLUSIONS: Liver-specific miR-122 supposed be a new marker molecule for early
      diagnosis of liver cells injury in the acute liver failure.

PMID- 20678446
TI  - [A new monoclonal antibody selectively distributes on hepatocellular membrane].
AB  - OBJECTIVE: Screening monoclonal antibodies selectively distribute on
      hepatocellular membrane by hybridoma technology and exploring their relationship
      with liver diseases. METHODS: Plasma membrane vesicles of rat hepatocytes were
      prepared using density gradient centrifugation and BALB/c mice were immunized
      with the membrane vesicles. Monoclonal antibodies were made with hybridoma
      technology. The immunizing valences and monoclonal antibodies were detected and
      screened by ELISA. Mh7 antigen was identified by immunoprecipitation method.
      Liver tissues of carbon tetrachloride injured rat models and diabetic rat models
      were used to detect the pathology value of mh7-antigen. RESULTS: Hepatocellular
      membrane vesicles were obtained successfully. Several monoclonal antibodies were
      yielded by hybridoma technology. Immunofluorescence and pre-embedding immunogold
      silver cytochemistry confirmed that mh7-antigen was a membrane molecule and with
      a 200KD molecular weight. Immunohistochemistry results indicated mh7 selectively
      distributed on hepatocellular membrane. Results with rat models demonstrated that
      mh7-antigen was dramatically reduced in fatty degenerated hepatocyte of carbon
      tetrachloride injured rat models and distributed as straps in diabetic rat
      models. CONCLUSIONS: Mh7 is a new hepatocellular membrane monoclonal antibody and
      may closely related with liver diseases.

PMID- 20678447
TI  - [Effects of the umbilical blood stem cell transplantation in patients with liver
      cirrhosis].

PMID- 20678448
TI  - [Relationship of heat shock protein 70-2 gene polymorphism with hepatocellular
      carcinoma].

PMID- 20678449
TI  - [Effect of adefovir and lamivudine combination therapy on lamivudine resistance
      chronic hepatitis B patients for 48 weeks].

PMID- 20678450
TI  - [Isolation and in vitro culture of bone marrow-derived mesenchymal stem cells].

PMID- 20678451
TI  - [FLK-1 in fetal mouse liver identifies a multipotent hepatic precursor which
      differentiates into cholangiocytes and hepatocytes].

PMID- 20678452
TI  - [The expression and significance of adenylate cyclase-associated protein 2 in
      human hepatocellular carcinoma].

PMID- 20678453
TI  - [The expression and significance of minichromosome maintenance proteins 2 in
      hepatocellular carcinoma].

PMID- 20678454
TI  - [Clinical characteristics of 38 cases of acute hepatitis B].

PMID- 20678455
TI  - [Severe intrahepatic cholestasis and hemochromatosis secondary to hereditary
      spherocytosis].

PMID- 20678456
TI  - [A report from the 20th conference of APASL].

PMID- 20678457
TI  - [Prevention of hepatitis B virus vertical transmission: current situation and
      challenges.].

PMID- 20678458
TI  - [The migration of hepatic stellate cell and epithelial to mesenchymal
      transition].

PMID- 20678460
TI  - Biophysical and chemical effects of fibrin on mesenchymal stromal cell gene
      expression.
AB  - Mesenchymal stromal cells (MSCs) are multipotent cells that have high expansion
      yields and fibrin is a native extracellular matrix (ECM) material widely used for
      cell delivery and surgery. MSCs and fibrin have tremendous potential for tissue
      engineering applications, but the effect of fibrin on MSCs is not well
      characterized. The purpose of this study was to analyze the role of fibrin in
      modulating MSC phenotype by gene expression analysis. The results demonstrate
      that fibrin up-regulated MSC gene expression of vasculogenic (FLK1, ACTA2, VECAD,
      SM22 and CNN1), myogenic (MYF5 and MYH13), neurogenic (TH and GFAP) and
      chondrogenic (COL2A1) markers after 5 days incubation. These gene expression
      results were supported by induction of expression on the protein level for early
      lineage-specific markers such as ACTA2, FLK1 and MYF5. The ability of fibrin to
      modulate MSC gene expression was not affected by matrix pore size (80-110 microm
      diameter) or Young's modulus (5-25k Pa) and the differential expression of some
      phenotypic markers could be partially mimicked by other ECM proteins, such as
      fibronectin and collagen I. In some cases the inductive effect of fibrin on gene
      expression could be further augmented by the treatment with growth factors such
      as nerve growth factor. However, the effect of fibrin appeared to be limited, as
      MSCs did not differentiate into fully mature cells based on immunofluorescence
      staining after 12 days. This body of work provides a rational approach for
      studying the interactions of MSC with fibrin, which has important therapeutic
      implications for the delivery of stem cells.

PMID- 20678461
TI  - Scientific, legal, and ethical challenges of end-of-life organ procurement in
      emergency medicine.
AB  - AIM: We review (1) scientific evidence questioning the validity of declaring
      death and procuring organs in heart-beating (i.e., neurological standard of
      death) and non-heart-beating (i.e., circulatory-respiratory standard of death)
      donation; (2) consequences of collaborative programs realigning hospital policies
      to maximize access of procurement coordinators to critically and terminally ill
      patients as potential donors on arrival in emergency departments; and (3) ethical
      and legal ramifications of current practices of organ procurement on patients and
      their families. DATA SOURCES: Relevant publications in peer-reviewed journals and
      government websites. RESULTS: Scientific evidence undermines the biological
      criteria of death that underpin the definition of death in heart-beating (i.e.,
      neurological standard) and non-heart-beating (i.e., circulatory-respiratory
      standard) donation. Philosophical reinterpretation of the neurological and
      circulatory-respiratory standards in the death statute, to avoid the appearance
      of organ procurement as an active life-ending intervention, lacks public and
      medical consensus. Collaborative programs bundle procurement coordinators
      together with hospital staff for a team-huddle and implement a quality
      improvement tool for a Rapid Assessment of Hospital Procurement Barriers in
      Donation. Procurement coordinators have access to critically ill patients during
      the course of medical treatment with no donation consent and with family or
      surrogates unaware of their roles. How these programs affect the medical care of
      these patients has not been studied. CONCLUSIONS: Policies enforcing end-of-life
      organ procurement can have unintended consequences: (1) erosion of care in the
      patient's best interests, (2) lack of transparency, and (3) ethical and legal
      ramifications of flawed standards of declaring death.

PMID- 20678462
TI  - Effects of Ethidium (homidium bromide) on female reproductive performance of
      laboratory-reared tsetse flies, Glossina morsitans morsitans Westwood (Diptera:
      Glossinidae).
AB  - Ethidium (homidium bromide) is a trypanocide likely to be encountered as a
      violative residue in blood collected from abattoirs for feeding laboratory tsetse
      flies. We investigated its effect on female reproduction of Glossina morsitans
      morsitans. One-milligram homidium per kilogram body weight was intra-muscularly
      administered to four steers and blood aseptically collected from them between 15
      and 30 min post-treatment, analysed for homidium levels and processed for tsetse
      feeding. Two hundred teneral female flies were fed on homidium-treated diet while
      a control group of similar number was given untreated diet and the reproductive
      performance of the two groups statistically compared. Ethidium, at 266.1 ng
      homidium/ml blood diet, halved A-class portion of F(1)-pupae, highly reduced
      decline of F(1)-progeny quality associated with aging parents, but had no
      significant effect on the pupae viability, fecundity and abortion rate of the
      flies. We therefore concluded that Ethidium has beneficial effect on laboratory
      tsetse attributable to clearance of unfavourable microbes mediated by the drug,
      and could be used as a tsetse diet additive.

PMID- 20678463
TI  - Amperometric immunosensor based on multiwalled carbon nanotubes/Prussian
      blue/nanogold-modified electrode for determination of alpha-fetoprotein.
AB  - In this article, a conspicuously simple and highly sensitive amperometric
      immunosensor based on the sequential electrodeposition of Prussian blue (PB) and
      gold nanoparticles (GNPs) on multiwalled carbon nanotube (MWCNT)-modified glassy
      carbon electrode (GCE) surface is proposed for the detection of alpha-fetoprotein
      (AFP). By comparison with PB, the MWCNT/PB composite film had been proven to show
      much better electrochemical stability and a larger response current. The
      electrodeposited GNP film can be used not only to immobilize biomolecules but
      also to avoid the leakage of PB and to prevent shedding of MWCNT/PB composite
      film from the electrode surface. The performance and factors influencing the
      performance of the immunosensor were investigated. Under optimal experimental
      conditions, the proposed immunosensor for AFP was observed with an ultralow limit
      of detection (LOD) equal to 3 pg/ml (at 3delta), and the linear working range
      spanned the concentrations of AFP from 0.01 to 300 ng/ml. Moreover, the
      immunosensor, as well as a commercially available kit, was examined for use in
      the determination of AFP in real human serum specimens. More significant, the
      assay mentioned here is simpler than the traditional enzyme-linked immunosorbent
      assay (ELISA), and an excellent correlation of levels of AFP measured was
      obtained, indicating that the developed immunoassay could be a promising
      alternative approach for detection of AFP and other tumor markers in the clinical
      diagnosis.

PMID- 20678464
TI  - Voltammetric determination of cefixime in pharmaceuticals and biological fluids.
AB  - Electroreduction and adsorption of cefixime was studied in phosphate buffer by
      cyclic voltammetry (CV), differential pulse cathodic adsorptive stripping
      voltammetry (DPCAdSV), and square-wave cathodic adsorptive stripping voltammetry
      (SWCAdSV) at hanging mercury drop electrode (HMDE). These fully validated
      sensitive and reproducible cathodic adsorptive stripping voltammetric procedures
      were applied for the trace determination of the bulk drug in pharmaceutical
      formulations and in human urine. The optimal experimental parameters were as
      follows: accumulation potential=-0.1 V (vs. Ag/AgCl, 3M KCl), accumulation
      time=50s, frequency=140 Hz, pulse amplitude=0.07 V, and scan increment=10 mV in
      phosphate buffer (pH 2.6). The first peak current showed a linear dependence with
      the drug concentration over the range of 50 ng ml(-1) to 25.6 MUg ml(-1). The
      achieved limit of detection and limit of quantitation were 3.99 and 13.3 ng ml(
      1) by SWCAdSV and 7.98 and 26.6 ng ml(-1) by DPCAdSV, respectively. The procedure
      was applied to assay the drug in tablets. Applicability was also tested in urine
      samples. Peak current was linear with the drug concentration in the range of 1 to
      60 MUg ml(-1) of the urine, and minimum detectability was found to be 12.6 ng ml(
      1) by SWCAdSV and 58.4 ng ml(-1) by DPCAdSV.

PMID- 20678465
TI  - Validation model for Raman based skin carotenoid detection.
AB  - Raman spectroscopy holds promise as a rapid objective non-invasive optical method
      for the detection of carotenoid compounds in human tissue in vivo. Carotenoids
      are of interest due to their functions as antioxidants and/or optical absorbers
      of phototoxic light at deep blue and near UV wavelengths. In the macular region
      of the human retina, carotenoids may prevent or delay the onset of age-related
      tissue degeneration. In human skin, they may help prevent premature skin aging,
      and are possibly involved in the prevention of certain skin cancers. Furthermore,
      since carotenoids exist in high concentrations in a wide variety of fruits and
      vegetables, and are routinely taken up by the human body through the diet, skin
      carotenoid levels may serve as an objective biomarker for fruit and vegetable
      intake. Before the Raman method can be accepted as a widespread optical
      alternative for carotenoid measurements, direct validation studies are needed to
      compare it with the gold standard of high performance liquid chromatography. This
      is because the tissue Raman response is in general accompanied by a host of other
      optical processes which have to be taken into account. In skin, the most
      prominent is strongly diffusive, non-Raman scattering, leading to relatively
      shallow light penetration of the blue/green excitation light required for
      resonant Raman detection of carotenoids. Also, sizable light attenuation exists
      due to the combined absorption from collagen, porphyrin, hemoglobin, and melanin
      chromophores, and additional fluorescence is generated by collagen and
      porphyrins. In this study, we investigate for the first time the direct
      correlation of in vivo skin tissue carotenoid Raman measurements with subsequent
      chromatography derived carotenoid concentrations. As tissue site we use heel
      skin, in which the stratum corneum layer thickness exceeds the light penetration
      depth, which is free of optically confounding chromophores, which can be easily
      optically accessed for in vivo RRS measurement, and which can be easily removed
      for subsequent biochemical measurements. Excellent correlation (coefficient
      R=0.95) is obtained for this tissue site which could serve as a model site for
      scaled up future validation studies of large populations. The obtained results
      provide proof that resonance Raman spectroscopy is a valid non-invasive objective
      methodology for the quantitative assessment of carotenoid antioxidants in human
      skin in vivo.

PMID- 20678466
TI  - The eccentric cleavage product of beta-carotene, beta-apo-13-carotenone,
      functions as an antagonist of RXRalpha.
AB  - In this study, we investigated the effects of eccentric cleavage products of beta
      carotene, i.e. beta-apocarotenoids (BACs), on retinoid X receptor alpha
      (RXRalpha) signaling. Transactivation assays were performed to test whether BACs
      activate or antagonize RXRalpha. Reporter gene constructs (RXRE-Luc, pRL-tk) and
      RXRalpha were transfected into Cos-1 cells and used to perform these assays. None
      of the BACs tested activated RXRalpha. Among the compounds tested, beta-apo-13
      carotenone was found to antagonize the activation of RXRalpha by 9-cis-retinoic
      acid and was effective at concentrations as low as 1 nM. Molecular modeling
      studies revealed that beta-apo-13-carotenone makes molecular interactions like an
      antagonist of RXRalpha. The results suggest a possible function of BACs on
      RXRalpha signaling.

PMID- 20678467
TI  - Studies on the singlet oxygen scavenging mechanism of human macular pigment.
AB  - It is thought that direct quenching of singlet oxygen and scavenging free
      radicals by macular pigment carotenoids is a major mechanism for their beneficial
      effects against light-induced oxidative stress. Corresponding data from human
      tissue remains unavailable, however. In the studies reported here, electron
      paramagnetic resonance (EPR) spectroscopy was used to measure light-induced
      singlet oxygen generation in post-mortem human macula and retinal pigment
      epithelium/choroid (RPE/choroid). Under white-light illumination, production of
      singlet oxygen was detected in RPE/choroid but not in macular tissue, and we show
      that exogenously added macular carotenoids can quench RPE/choroid singlet oxygen.
      When the singlet oxygen quenching ability of the macular carotenoids was
      investigated in solution, it was shown that a mixture of meso-zeaxanthin,
      zeaxanthin, and lutein in a ratio of 1:1:1 can quench more singlet oxygen than
      the individual carotenoids at the same total concentration.

PMID- 20678468
TI  - Reduction of oxidized guanosine by dietary carotenoids: a pulse radiolysis study.
AB  - Time-resolved pulse radiolysis investigations reported herein show that the
      carotenoids beta-carotene, lycopene, zeaxanthin and astaxanthin (the last two are
      xanthophylls--oxygen containing carotenoids) are capable of both reducing
      oxidized guanosine as well as minimizing its formation. The reaction of the
      carotenoid with the oxidized guanosine produces the radical cation of the
      carotenoid. This behavior contrasts with the reactions between the amino acids
      and dietary carotenoids where the carotenoid radical cations oxidized the amino
      acids (tryptophan, cysteine and tyrosine) at physiological pH.

PMID- 20678469
TI  - Phosphoinositide 3-kinase-gamma expression is upregulated in brain microglia and
      contributes to ischemia-induced microglial activation in acute experimental
      stroke.
AB  - Microglia, the resident microphages of the CNS, are rapidly activated after
      ischemic stroke. Inhibition of microglial activation may protect the brain by
      attenuating blood-brain barrier damage and neuronal apoptosis after ischemic
      stroke. However, the mechanisms by which microglia is activated following
      cerebral ischemia is not well defined. In this study, we investigated the
      expression of PI3Kgamma in normal and ischemic brains and found that PI3Kgamma
      mRNA and protein are constitutively expressed in normal brain microvessels, but
      significantly upregulated in postischemic brain primarily in activated microglia
      following cerebral ischemia. In vitro, the expression of PI3Kgamma mRNA and
      protein was verified in mouse brain endothelial and microglial cell lines.
      Importantly, absence of PI3Kgamma blocked the early microglia activation (at 4h)
      and subsequent expansion (at 24-72 h) in PI3Kgamma knockout mice. The results
      suggest that PI3Kgamma is an ischemia-responsive gene in brain microglia and
      contributes to ischemia-induced microglial activation and expansion.

PMID- 20678470
TI  - Tyrosine phosphorylation of vinculin at position 1065 modifies focal adhesion
      dynamics and cell tractions.
AB  - Focal adhesions (FAs) connect the cellular actin cytoskeleton via integrin with
      the extracellular matrix. They comprise of many structural and signaling proteins
      which are highly dynamic, well regulated, and responsible for the sensing of
      physical properties from the environment. Vinculin is a protein that incorporates
      all these functions. Here, we investigated the phosphorylation of Y1065 in the
      activation/regulation of vinculin. We used different vinculin mutants mimicking
      either a permanently activated or inhibited phosphorylation site at position
      1065. Using these mutants, we determined their influence on the exchange dynamics
      and cell forces using fluorescence recovery after photobleaching and traction
      microscopy. The results indicate that phosphorylation at Y1065 significantly
      increases the amount of freely exchanging vinculin within FAs whereas inhibition
      of this phosphorylation site leads to an uncontrolled exchange of vinculin and
      reduced adhesive cell forces. In conclusion, we show that phosphorylation on
      position Y1065 is essential for accurate incorporation of vinculin into FAs and
      mechanical behavior of cells.

PMID- 20678471
TI  - Misoprostol elevates intracellular calcium in Neuro-2a cells via protein kinase
      A.
AB  - Misoprostol, a prostaglandin type E analogue, has been implicated in a number of
      neurodevelopmental disorders. However, its mode of action in the nervous system
      is not well understood. Misoprostol acts on the same receptors as prostaglandin
      E(2) (PGE(2)), a natural lipid-derived compound, which mediates important
      physiological functions in the nervous system via activation of four EP receptors
      (EP1-4). In this study we use a ratiometric calcium imaging with fura-2 AM as a
      calcium indicator to show that misoprostol alters intracellular calcium levels in
      mouse neuroblastoma (Neuro-2a) cells via similar mechanisms as PGE(2). We
      demonstrate that the misoprostol-induced increase in calcium is mediated by a
      protein kinase A (PKA)-dependent mechanism and that the EP4 receptor signaling
      pathway may play an inhibitory role on calcium regulation. Overall, this study
      provides further support for the involvement of PGE(2) signaling in calcium
      homeostasis and suggests its important role in the nervous system.

PMID- 20678472
TI  - Sanguinarine induces apoptosis of human osteosarcoma cells through the extrinsic
      and intrinsic pathways.
AB  - The quaternary benzo[c]phenanthridine alkaloid sanguinarine inhibits the
      proliferation of cancerous cells from different origins, including lung, breast,
      pancreatic and colon, but nothing is known of its effects on osteosarcoma, a
      primary malignant bone tumour. We have found that sanguinarine alters the
      morphology and reduces the viability of MG-63 and SaOS-2 human osteosarcoma cell
      lines in concentration- and time-dependent manner. Incubation with 1 micromol/L
      sanguinarine for 4 and 24h killed more efficiently MG-63 cells than SaOS-2 cells,
      while incubation with 5 micromol/L sanguinarine killed almost 100% of both cell
      populations within 24h. This treatment also changed the mitochondrial membrane
      potential in both MG-63 and SaOS-2 cells within 1h, caused chromatin condensation
      and the formation of apoptotic bodies. It activated multicaspases, and increased
      the activities of caspase-8 and caspase-9 in both MG-63 and SaOS-2 cells. These
      data highlight sanguinarine as a novel potential agent for bone cancer therapy.

PMID- 20678473
TI  - Impaired pancreatic development in Hif2-alpha deficient mice.
AB  - Accumulating data suggest the existence of a link between hypoxia and maintenance
      of the undifferentiated cell state, but little is known about the cellular
      signaling mechanisms underlying this process. Recent reports reveal a direct link
      between components of the hypoxia signaling pathway and Notch pathway in
      maintaining precursor cells in an undifferentiated state. Here, we report that in
      the developing mouse pancreas, Hif2-alpha is expressed in pancreatic progenitor
      cells, but its expression is lost in committed endocrine progenitors as well as
      in differentiated endocrine and exocrine cells. In an attempt to analyze the
      function of HIF2-alpha in the developing pancreas, we studied Hif2-alpha(-/-)
      pancreas. Our analyses revealed that in addition to the decreased size and
      branching, the Hif2-alpha deficient pancreas also displayed impaired notch
      signaling and cell differentiation. Finally, we found that HIF2-alpha binds
      directly to Notch-IC and that the responsible site for this interaction is within
      the RAM domain of Notch protein. These results suggest that HIF2-alpha is
      required for normal mouse pancreatic development.

PMID- 20678474
TI  - Interleukin-1beta regulates cell proliferation and activity of extracellular
      matrix remodelling enzymes in cultured primary pig heart cells.
AB  - After myocardial infarction, elevated levels of interleukins (ILs) are found
      within the myocardial tissue and IL-1beta is considered to play a major role in
      tissue remodelling events throughout the body. In the study presented, we have
      established a cell culture model of primary pig heart cells to evaluate the
      effects of different concentrations of IL-1beta on cell proliferation as well as
      expression and activity of enzymes typically involved in tissue remodelling.
      Primary pig heart cell cultures were derived from three different animals and
      stimulated with recombinant pig IL-1beta. RNA expression was detected by RT-PCR,
      protein levels were evaluated by Western blotting, activity of matrix
      metalloproteinases (MMPs) was quantified by gelatine zymography and cell
      proliferation was measured using colorimetric MTS assays. Pig heart cells express
      receptors for IL-1 and application of IL-1beta resulted in a dose-dependent
      increase of cell proliferation (P<0.05 vs. control; 100ng/ml; 24h). Gene
      expression of caspase-3 was increased by IL-1beta (P<0.05 vs. control; 100ng/ml;
      3h), and pro-caspase-3 but not active caspase was detected in lysates of pig
      heart cells by Western blotting. MMP-2 gene expression as well as enzymatic
      activities of MMP-2 and MMP-9 were increased by IL-1beta (P<0.05 vs. control;
      100ng/ml; 3h for gene expression, 48 and 72h for enzymatic activities of MMP-2
      and MMP-9, respectively). Our in vitro data suggest that IL-1beta plays a major
      role in the events of tissue remodelling in the heart. Combined with our recently
      published in vivo data (Meybohm et al., PLoS One, 2009), the results presented
      here strongly suggest IL-1beta as a key molecule guiding tissue remodelling
      events after myocardial infarction.

PMID- 20678475
TI  - Dynamics of lipid droplets induced by the hepatitis C virus core protein.
AB  - The hepatitis C virus (HCV) is a global health problem, with limited treatment
      options and no vaccine available. HCV uses components of the host cell to
      proliferate, including lipid droplets (LD) onto which HCV core proteins bind and
      facilitate viral particle assembly. We have measured the dynamics of HCV core
      protein-mediated changes in LDs and rates of LD movement on microtubules using a
      combination of coherent anti-Stokes Raman scattering (CARS), two-photon
      fluorescence (TPF), and differential interference contrast (DIC) microscopies.
      Results show that the HCV core protein induces rapid increases in LD size.
      Particle tracking experiments show that HCV core protein slowly affects LD
      localization by controlling the directionality of LD movement on microtubules.
      These dynamic processes ultimately aid HCV in propagating and the molecules and
      interactions involved represent novel targets for potential therapeutic
      intervention.

PMID- 20678476
TI  - Substrate cleavage pattern, biophysical characterization and low-resolution
      structure of a novel hyperthermostable arabinanase from Thermotoga petrophila.
AB  - Arabinan is a plant structural polysaccharide degraded by two enzymes; alpha-l
      arabinofuranosidase and endo-1,5-alpha-l-arabinanase. These enzymes are highly
      diversified in nature, however, little is known about their biochemical and
      biophysical properties. We have characterized a novel arabinanase (AbnA) isolated
      from Thermotoga petrophila with unique thermostable properties such as the
      insignificant decrease of residual activity after incubation up to 90 degrees C.
      We determined the AbnA mode of operation through capillary zone electrophoresis,
      which accumulates arabinotriose and arabinobiose as end products after hydrolysis
      of arabinan-containing polysaccharides. Spectroscopic analyses by Far-UV circular
      dichroism and intrinsic tryptophan fluorescence emission demonstrated that AbnA
      is folded and formed mainly by beta-sheet structural elements. In silico
      molecular modeling showed that the AbnA structure encompasses a five-bladed beta
      propeller catalytic core juxtaposed by distorted up-and-down beta-barrel domain.
      The low-resolution structure determined by small angle X-ray scattering indicated
      that AbnA is monomeric in solution and its molecular shape is in full agreement
      with the model.

PMID- 20678477
TI  - Performance assessment of protein multiple sequence alignment algorithms based on
      permutation similarity measurement.
AB  - Protein multiple sequence alignment is an important bioinformatics tool. It has
      important applications in biological evolution analysis and protein structure
      prediction. A variety of alignment algorithms in this field have achieved great
      success. However, each algorithm has its own inherent deficiencies. In this
      paper, permutation similarity is proposed to evaluate several protein multiple
      sequence alignment algorithms that are widely used currently. As the permutation
      similarity method only concerns the relative order of different protein
      evolutionary distances, without taking into account the slight difference between
      the evolutionary distances, it can get more robust evaluations. The longest
      common subsequence method is adopted to define the similarity between different
      permutations. Using these methods, we assessed Dialign, Tcoffee, ClustalW and
      Muscle and made comparisons among them.

PMID- 20678478
TI  - Variable loss of Kir4.1 channel function in SeSAME syndrome mutations.
AB  - SeSAME syndrome is a complex disease characterized by seizures, sensorineural
      deafness, ataxia, mental retardation and electrolyte imbalance. Mutations in the
      inwardly rectifying potassium channel Kir4.1 (KCNJ10 gene) have been linked to
      this condition. Kir4.1 channels are weakly rectifying channels expressed in glia,
      kidney, cochlea and possibly other tissues. We determined the
      electrophysiological properties of SeSAME mutant channels after expression in
      transfected mammalian cells. We found that a majority of mutations (R297C, C140R,
      R199X, T164I) resulted in complete loss of Kir4.1 channel function while two
      mutations (R65P and A167V) produced partial loss of function. All mutant channels
      were rescued upon co-transfection of wild-type Kir4.1 but not Kir5.1 channels.
      Cell-surface biotinylation assays indicate significant plasma membrane expression
      of all mutant channels with exception of the non-sense mutant R199X. These
      results indicate the differential loss of Kir channel function among SeSAME
      syndrome mutations.

PMID- 20678479
TI  - Selection and evaluation of stable housekeeping genes for gene expression
      normalization in carbon nanoparticle-induced acute pulmonary inflammation in
      mice.
AB  - Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) is a
      highly specific and sensitive technique for the quantification of gene expression
      on the mRNA levels. But use of unconfirmed housekeeping genes (HKGs) could lead
      to misinterpretation of the expression of genes of interest (GOI). In this study,
      the stability and suitability of 11 frequently used housekeeping genes, namely
      18S rRNA, ACTB, B2M, CYPA, GADPH, GUSB, HMBS, HPRT1, RPL13A, SDHA and TBP in 36
      lung tissues isolated from either wild-type (WT) mice or p50 knock out (p50-/-)
      mice or p105 knock-out (p105-/-) mice which were treated with either carbon
      nanoparticle (CNP) or H(2)O or non-treated, have been validated by geNorm,
      NormFinder and BestKeeper programs. The expression levels of ACTB, GUSB and
      RPL13A were the most constant in lung tissues across three genotypes and three
      kinds of treatments. A set of three most stable genes is found sufficient to be
      used as housekeeping genes for lung tissues in studies of similar design.

PMID- 20678480
TI  - Subcellular localization of the interaction of bipolar landmarks Bud8p and Bud9p
      with Rax2p in Saccharomyces cerevisiae diploid cells.
AB  - In Saccharomyces cerevisiae, the bud site selection of diploid cells is regulated
      by at least four persistent landmarks, Bud8p, Bud9p, Rax1p, and Rax2p. Bud8p and
      Bud9p are essential for the establishment of bipolar budding and localize mainly
      to the distal and the proximal poles, respectively. Their subcellular
      localizations are regulated through interaction with Rax1p/Rax2p. We investigated
      when and where Bud8p and Bud9p physically interact with Rax2p in vivo using a
      split-GFP method. GFP fluorescence showed that Bud8p physically interacted with
      Rax2p at the proximal or distal pole in unbudded cells; a physical interaction
      was also observed at the opposite pole to the growing bud in mother cells with a
      large-size bud. Bud9p physically interacted with Rax2p at the birth scar in
      budded mother cells. These observations suggest that the interaction of Rax2p
      with Bud8p and Bud9p may contribute to the translocation of bipolar landmarks to
      the correct sites.

PMID- 20678481
TI  - Phase separation in lipid bilayers triggered by low pH.
AB  - Endocytosis involves the capture of membrane from the cell surface in the form of
      vesicles, which become rapidly acidified to about pH 5. Here we show using atomic
      force microscopy (AFM) imaging that this degree of acidification triggers phase
      separation in lipid bilayers containing mixed acyl chains (e.g. palmitoyl/oleoyl)
      or complex mixtures (e.g. total brain extract) but not in bilayers containing
      only lipids with unsaturated chains (e.g. dioleoyl). Since mixed-chain lipids are
      major constituents of the outer leaflet of the plasma membrane, the type of phase
      separation reported here might support protein clustering and signaling during
      endocytosis.

PMID- 20678482
TI  - Crystal structure of the ligand-binding domain of the promiscuous EphA4 receptor
      reveals two distinct conformations.
AB  - Eph receptors and their ephrin ligands are important mediators of cell-cell
      communication. They are divided in two subclasses based on their affinities for
      each other and on sequence conservation. Receptor-ligand binding within each
      subclass is fairly promiscuous, while binding cross the subclasses happens
      rarely. EphA4 is an exception to this general rule, since it has long been known
      to bind both A- and B-class ephrin ligands but the reason for this exceptional
      behavior has not been worked out at molecular level. Recent structural and
      biochemical studies on EphA4 ligand-binding domain alone and in complex with its
      ligands have addressed this question. However, the published structures of
      EphA4/ephrin complexes differ considerably from each other and strikingly
      different explanations for the exceptional promiscuity of EphA4 were proposed. To
      address these contradictory findings, we have determined a crystal structure of
      the EphA4 ligand-binding domain at 2.3A resolution and show that the receptor has
      an unprecedented ability to exist in two very different, well-ordered
      conformations even in the unbound state. Our results suggest that the ligand
      promiscuity of the Ephs is directly correlated with the structural flexibility of
      the ligand-binding surface of the receptor.

PMID- 20678483
TI  - Integrin alpha8beta1 confers anoikis susceptibility to human intestinal
      epithelial crypt cells.
AB  - We previously reported that integrin alpha8beta1 is expressed in human intestinal
      epithelial crypt cells (HIECs) and represents one of the major RGD-binding
      integrins expressed by these cells. Moreover, the depletion of alpha8beta1
      affects vinculin, but not paxillin, localization at focal adhesion points. In the
      present study, we show that the integrin alpha8 shRNA-mediated knockdown in HIECs
      leads to a decrease in anoikis susceptibility under cell suspension culture
      conditions, marked by a reduction in PARP cleavage and propidium iodide
      incorporation. Moreover, alpha8beta1-depleted HIECs exhibited an illicitly
      sustained activation of Fak and PI3-K/Akt-1 under anoikis conditions, rendering
      them refractory to anoikis. To this effect, colon cancer cells exhibiting
      resistance to anoikis not only displayed a loss of alpha8beta1 expression, but
      forced expression of alpha8beta1 in these cells decreased their resistance to
      anoikis. Consequently, alpha8beta1 is a prerequisite for the proper conduct of
      anoikis in normal HIECs, whereas its loss contributes to the illicit acquisition
      of anoikis resistance.

PMID- 20678484
TI  - Mitochondrial remodeling following fission inhibition by 15d-PGJ2 involves
      molecular changes in mitochondrial fusion protein OPA1.
AB  - We showed earlier that 15 deoxy Delta(12,14) prostaglandin J2 (15d-PGJ2)
      inactivates Drp1 and induces mitochondrial fusion [1]. However, prolonged
      incubation of cells with 15d-PGJ2 resulted in remodeling of fused mitochondria
      into large swollen mitochondria with irregular cristae structure. While initial
      fusion of mitochondria by 15d-PGJ2 required the presence of both outer (Mfn1 and
      Mfn2) and inner (OPA1) mitochondrial membrane fusion proteins, later
      mitochondrial changes involved increased degradation of the fusion protein OPA1
      and ubiquitination of newly synthesized OPA1 along with decreased expression of
      Mfn1 and Mfn2, which likely contributed to the loss of tubular rigidity,
      disorganization of cristae, and formation of large swollen degenerated
      dysfunctional mitochondria. Similar to inhibition of Drp1 by 15d-PGJ2, decreased
      expression of fission protein Drp1 by siRNA also resulted in the loss of fusion
      proteins. Prevention of 15d-PGJ2 induced mitochondrial elongation by thiol
      antioxidants prevented not only loss of OPA1 isoforms but also its
      ubiquitination. These findings provide novel insights into unforeseen complexity
      of molecular events that modulate mitochondrial plasticity.

PMID- 20678485
TI  - A lysine-rich region in Dot1p is crucial for direct interaction with H2B
      ubiquitylation and high level methylation of H3K79.
AB  - Dot1p is involved in maintenance of the heterochromatin boundary, the DNA damage
      response, and transcriptional regulation in yeast and animals. Dot1p is a histone
      H3 lysine 79 (H3K79) methyltransferase, but H3K79 trimethylation (H3K79me3) by
      Dot1p requires histone H2B monoubiquitylation (H2Bub) as a pre-requisite. The
      underlying mechanism for H2Bub requirement has not been well elucidated. In this
      work, we found that nucleosomes containing H2Bub stimulate the yeast Dot1p to
      produce H3K79me3. A pulldown assay showed that the yeast Dot1p directly binds to
      ubiquitin. In addition, we demonstrate that a lysine-rich region (aa 101-140) in
      the first half of DNA binding domain of the Dot1p is critical in interaction with
      ubiquitin as well as binding to nucleosome core. Consistent with this, either
      deletion or point mutation of the lysine-rich region resulted in defect in global
      H3K79me3 accumulation and subtelomeric gene silencing in vivo. Taken together,
      our results indicate that a direct interaction between the lysine-rich region of
      Dot1p and the ubiquitin of H2Bub is required for H2Bub-mediated trans-tail
      regulation.

PMID- 20678486
TI  - Tensin2 reduces intracellular phosphatidylinositol 3,4,5-trisphosphate levels at
      the plasma membrane.
AB  - Tensins are proposed cytoskeleton-regulating proteins. However, Tensin2
      additionally inhibits Akt signalling and cell survival. Structural modelling of
      the Tensin2 phosphatase (PTPase) domain revealed an active site-like pocket
      receptive towards phosphoinositides. Tensin2-expressing HEK293 cells displayed
      negligible levels of plasma membrane phosphatidylinositol 3,4,5-trisphosphate
      (PtdIns(3,4,5)P(3)) under confocal microscopy. However, mock-transfected cells,
      and Tensin2 cells harbouring a putative phosphatase-inactivating mutation,
      exhibited significant PtdIns(3,4,5)P(3) levels, which decreased upon
      phosphatidylinositol 3-kinase inhibition with LY294002. In contrast, wtTensin3,
      mock and mutant cells were identical in membrane PtdIns(3,4,5)P(3) and Akt
      phosphorylation. In vitro lipid PTPase activity was however undetectable in
      isolated recombinant PTPase domains of both Tensins, indicating a possible loss
      of structural stability when expressed in isolation. In summary, we provide
      evidence that Tensin2, in addition to regulating cytoskeletal dynamics,
      influences phosphoinositide-Akt signalling through its PTPase domain.

PMID- 20678487
TI  - Amphotericin B inhibits entry of Leishmania donovani into primary macrophages.
AB  - Visceral leishmaniasis is a vector-borne disease caused by an obligate intra
      macrophage protozoan parasite Leishmania donovani. The molecular mechanisms
      involved in internalization of Leishmania are still poorly understood.
      Amphotericin B and its formulations are considered as the best existing drugs
      against visceral leishmaniasis and are being increasingly used. The reason for
      its antileishmanial activity is believed to be its ability to bind ergosterol
      found in parasite membranes. In case of in vivo amphotericin B treatment, both
      host macrophages and parasites are exposed to amphotericin B. The effect of
      amphotericin B treatment could therefore be due to a combination of its
      interaction with both sterols i.e., ergosterol of Leishmania and cholesterol of
      host macrophages. We report here that cholesterol complexation by amphotericin B
      markedly inhibits binding of L. donovani promastigotes to macrophages. These
      results represent one of the first reports on the effect of amphotericin B on the
      binding of Leishmania parasites to host macrophages. Importantly, these results
      offer the possibility of reevaluating the mechanism behind the effectiveness of
      current therapeutic strategies that employ sterol-complexing agents such as
      amphotericin B to treat leishmaniasis.

PMID- 20678488
TI  - Prediction of protein subcellular localization by weighted gene ontology terms.
AB  - We develop a new weighting approach of gene ontology (GO) terms for predicting
      protein subcellular localization. The weights of individual GO terms,
      corresponding to their contribution to the prediction algorithm, are determined
      by the term-weighting methods used in text categorization. We evaluate several
      term-weighting methods, which are based on inverse document frequency,
      information gain, gain ratio, odds ratio, and chi-square and its variants.
      Additionally, we propose a new term-weighting method based on the logarithmic
      transformation of chi-square. The proposed term-weighting method performs better
      than other term-weighting methods, and also outperforms state-of-the-art
      subcellular prediction methods. Our proposed method achieves 98.1%, 99.3%, 98.1%,
      98.1%, and 95.9% overall accuracies for the animal BaCelLo independent dataset
      (IDS), fungal BaCelLo IDS, animal Hoglund IDS, fungal Hoglund IDS, and PLOC
      dataset, respectively. Furthermore, the close correlation between high-weighted
      GO terms and subcellular localizations suggests that our proposed method
      appropriately weights GO terms according to their relevance to the localizations.

PMID- 20678489
TI  - Modulation of the cortical false belief network during development.
AB  - The ability to represent false beliefs is commonly considered as to be the
      critical test for having a Theory of Mind (ToM). For correct predictions or
      explanations of other peoples' behavior it is necessary to understand that mental
      states are sometimes independent of reality and misrepresent the real state of
      the world. In contrast, when people hold true beliefs, predictions and
      explanations about behavior can simply be derived from reality. Previous
      neuroimaging studies with adults suggest that the dorsal medial prefrontal cortex
      (dmPFC) and the right temporo-parietal junction (rTPJ) are engaged in false
      belief reasoning. However, studies investigating the neural correlates of belief
      reasoning in children are rare. Using cartoon stories that depicted an unexpected
      transfer, we compared false belief reasoning with true belief reasoning in
      children of a narrow age range between 10 and 12years and in adults. In both
      groups, the dorsal medial frontal cortex was activated during false versus true
      belief reasoning. In contrast to adults, children did not selectively recruit the
      rTPJ during false belief reasoning. We found a group by belief interaction in the
      right rostral PFC and the posterior cingulate cortex. In these areas, children
      compared to adults showed increased activity associated with false belief
      reasoning in contrast to true belief reasoning. These results implicate
      modulation of the cortical network that underlies false belief reasoning during
      development and far beyond the time children successfully master false belief
      tasks.

PMID- 20678490
TI  - Hippocampal involvement in working memory encoding of changing locations: an fMRI
      study.
AB  - Whereas the role of the hippocampus for spatial learning and long-term memory is
      largely undisputed, there is less evidence for a participation of hippocampal
      structures in spatial working memory operations. In an fMRI study (functional
      magnetic resonance imaging), we therefore examined the role of the hippocampus
      during spatial working memory performance. Nineteen healthy volunteers performed
      a modified version of the Corsi Block-Tapping test (CBT) during fMRI. The CBT is
      a neuropsychological instrument that is widely used in clinical settings. It
      requires the storage and subsequent reproduction of spatial target sequences.
      Brain activity during CBT performance has rarely been examined in the past, at
      least not the hemodynamic correlates. In a baseline condition, participants
      processed a number of subsequently presented targets as in the CBT condition. The
      only difference was that targets did not change their location. As compared to
      baseline activity, the right hippocampus showed more activation during the CBT
      condition. In addition, whole-brain analysis showed working memory related
      frontal and parietal brain activation. The results indicate that hippocampal
      structures contribute to serial working memory encoding of spatial locations in
      the human brain.

PMID- 20678491
TI  - Melatonin promotes distal dendritic ramifications in layer II/III cortical
      pyramidal cells of rats exposed to toluene vapors.
AB  - We have previously shown that toluene inhalation produces significant impairments
      in the basilar dendritic outgrowth of pyramidal cortical cells. This neurotoxic
      effect was markedly inhibited by melatonin administration at a dose of 5mg kg(
      1). The present study was designed to determine whether toluene and melatonin
      equally affect all basilar dendritic segments or if a differential response
      exists between the segments. Twenty-eight male mice were weaned at postnatal day
      21 (P21) and randomly assigned to either the control (C; n=10,) or toluene (T;
      n=18) group. Between P22-P32, male rats were placed into a glass chamber and
      exposed to either toluene vapors (5-000-6000 ppm) or clean air for 10 min a day.
      When toluene exposure ended (P32), animals were further assigned to the following
      experimental groups: (a) control/saline (C/S; n=10), (b) toluene/saline (T/S;
      n=10), or (c) toluene/melatonin 5mg kg(-1) (T/M; n=8). Melatonin or vehicle
      solutions were administered daily between P32 and P38. Forty-eight hours after
      the final toluene exposure, the animals were sacrificed, and the pyramidal
      cortical cells were stained using the Golgi-Cox-Sholl procedure. The number of
      basilar dendritic branches/order was counted using the centrifugal ordering
      method. The results indicate that (i) toluene inhalation significantly impairs
      both proximal and distal basilar dendritic ramifications (in the parietal and
      frontal/occipital cortices, respectively) and (ii) melatonin both protects
      neurons from toluene neurotoxicity in all cortical areas studied and increases
      the complexity of the dendritic tree above control values.

PMID- 20678492
TI  - Cyclothiazide induces seizure behavior in freely moving rats.
AB  - We have previously demonstrated that cyclothiazide (CTZ) is a potent convulsant
      drug inducing robust epileptiform activity in hippocampal neurons both in vitro
      and in vivo. Here we further establish an animal model for CTZ-induced behavioral
      seizures in freely moving rats. Microinjection of CTZ into the left ventricle
      dose-dependently induced robust seizure behaviors within 3h after administration.
      At a dose of 0.75 MUmol, CTZ induced Racine score IV-V seizure behaviors in 71%
      (n=14) of the rats were tested. In addition, CTZ also induced epileptiform EEG
      activity accompanying behavioral seizures. The convulsant action of CTZ on both
      behavior and EEG was blocked by pretreatment with clinical anticonvulsant drug
      diazepam (n=5). In conclusion, our results demonstrate that CTZ is capable of
      inducing behavioral seizures in intact animals. Since CTZ acts on both GABAergic
      and glutamatergic systems, this new animal epilepsy model will be useful for
      anticonvulsant drug testing and general epilepsy research.

PMID- 20678493
TI  - The effects of dose and route of administration of PSI on behavioural and
      biochemical indices of neuronal degeneration in the rat brain.
AB  - Repeated subcutaneous administration of proteasome inhibitor 1 [PSI, Z-Ile
      Glu(OtBu)-Ala-Leu-CHO] to rats causes progressive motor deficits and nigral
      dopaminergic cell loss in our laboratories, but this is controversial since
      others have not reproduced these findings. For this reason, we have investigated
      the role that the dose of PSI and its route of administration have on motor
      activity and neuronal loss in rat brain. PSI (8, 12 or 16 mg/kg, s.c.) was
      administered to female Wistar rats on 6 occasions on alternative days over 2
      weeks. Subsequently PSI (8 mg/kg) was administered by oral, s.c. and i.p. routes
      on alternate days to separate groups of animals. Rats were assessed for motor
      function on a weekly basis up to 5 months after the end of PSI treatment.
      Locomotor activity was decreased following s.c. administration of 8 and 12 mg/kg
      PSI but not following 16 mg/kg. In subsequent experiments PSI (8 mg/kg) decreased
      motor activity after p.o. but not i.p. administration. PSI 8 mg/kg s.c. or p.o.,
      but not i.p., caused neuronal loss in the substantia nigra, raphe nuclei, locus
      coeruleus, nucleus basalis of Meynert and dorsal motor nucleus of vagus. These
      data confirm that systemic administration of PSI reduces locomotor activity in
      rats and induces widespread neuronal degeneration in brain. However, the effects
      of PSI and its time course of action are dose and route dependent.

PMID- 20678494
TI  - Differences in cerebral activation during perception of optokinetic computer
      stimuli and video clips of living animals: an fMRI study.
AB  - AIMS: There is behavioral evidence of increased spontaneous recruitment of visual
      attention to ancestral evolved categories, such as animals, compared with
      expertise-derived categories, such as a computer. In order to investigate the
      association between visual perception and spontaneous visual attention, a study
      was performed to determine if brain activation whilst viewing moving animals was
      increased compared with optokinetic computer stimuli. METHODS: Functional MRI was
      performed in 12 healthy volunteers using a standard block-design paradigm,
      consisting of three consecutive experiments. Subjects viewed the following
      images: Experiment one--optokinetic computer stimuli alternating with static
      computer stimuli; Experiment two--moving animals alternating with non-moving
      animals; Experiment three--moving animals alternating with optokinetic computer
      stimuli. RESULTS: Moving animals evoked motion-dependent activation bilaterally
      in the middle and superior temporal gyri, right inferior temporal gyrus, left
      occipital gyrus, right supramarginal gyrus, and left straight gyrus. Integrated
      object-and-motion-dependent activation was found bilateral in inferior and middle
      temporal gyri, right superior temporal gyrus, right superior parietal lobule,
      left dorsal putamen, and right amygdala. CONCLUSIONS: These results suggest that
      there is increased cerebral activity in the visuo-attentional network whilst
      viewing moving animals compared with optokinetic computer stimuli.

PMID- 20678495
TI  - Mechanisms involved in the gastroprotective activity of esculin on acute gastric
      lesions in mice.
AB  - This work describes the gastroprotective actions of esculin (6,7
      dihydroxycoumarin-6-o-glucoside) against indomethacin- or ethanol-induced lesions
      and verifies the role of nitric oxide, ATP-dependent K(+) channels,
      prostaglandins, transient receptor potential vanilloid 1 and antioxidant effects
      in the gastroprotective mechanism of esculin in the ethanol-induced gastric
      lesion model. The intragastric administration of esculin at doses of 12.5, 25 and
      50 mg/kg was able to protect the gastric mucosa against ethanol (0.2 mL/animal
      p.o.), and esculin at doses of 25 and 50 mg/kg protected against indomethacin
      induced lesions (20mg/kg p.o.). Administration of l-NAME (10mg/kg i.p.),
      glibenclamide (10mg/kg i.p.) or indomethacin (10mg/kg p.o.), but not capsazepine
      (5mg/kg p.o.), was able to reduce the gastroprotection promoted by esculin
      (25mg/kg) on the ethanol-induced lesions. Measurements of nitrite, a NO
      metabolite, were increased in the group that was pretreated with esculin. In
      terms of antioxidant activity as a gastroprotective mechanism of esculin, the
      results show that pre-treatment with esculin decreased the amount of GSH,
      increased SOD activity, did not interfere with the CAT activity and decreased
      both the MPO activity and the MDA amount. In conclusion, pre-treatment with
      esculin confers significant gastroprotective and antioxidant activity and leads
      to a reduction in gastric injury; the mechanisms underlying these effects include
      stimulation of endogenous prostaglandins, nitric oxide synthesis, opening of
      K(ATP) channels and reduction of free radicals or modulation of antioxidant
      enzyme systems.

PMID- 20678496
TI  - Kallikrein-related peptidase 13 (KLK13) gene expressional status contributes
      significantly in the prognosis of primary gastric carcinomas.
AB  - OBJECTIVES: Gastric cancer is a fatal human malignancy with poor prognosis.
      Modifications in gene expression, including those of the kallikrein-related
      peptidase family, have been portrayed in gastric carcinogenesis. Given KLK13
      involvement in human malignancies, we aimed to uncover its prognostic strength in
      stomach cancer. DESIGN AND METHODS: Quantitative analysis of KLK13 profiles was
      accomplished in human gastric cancer cells and in a statistically significant
      sample size of stomach tissue specimens with the development of the highly
      sensitive real-time PCR methodology. RESULTS: Decreased KLK13 expression was
      demonstrated in cancerous compared with their matching non-malignant pairs
      (p=0.002) and in poorly differentiated gastric tumors (p=0.029). KLK13-positive
      patients were shown to live considerably longer (p=0.014) and with low risk of
      disease recurrences (p=0.043). CONCLUSIONS: This is the first study disclosing
      the possible clinical utility of KLK13 as a new tumor biomarker capable of
      predicting a favorable outcome for gastric cancer patients.

PMID- 20678498
TI  - The mammalian verprolin, WIRE induces filopodia independent of N-WASP through
      IRSp53.
AB  - The mammalian verprolin family of proteins, WIP (WASP Interacting Protein), CR16
      (Corticoid Regulated) and WIRE (WIp-RElated) regulate the actin cytoskeleton
      through WASP/N-WASP (Wiskott Aldrich Syndrome Protein and Neural-WASP). In order
      to characterize the WASP/N-WASP-independent function of WIRE, we screened and
      identified IRSp53 (Insulin Receptor Substrate) as a WIRE interacting protein.
      Expression of IRSp53 with WIRE in N-WASP(-/-) mouse fibroblast cells induced
      filopodia while co-expression of IRSp53 with WIP did not. The induction of
      filopodia is dependent on WIRE-IRSp53 interaction as mutation in the SH3 domain
      of IRSp53 abolished WIRE-IRSp53 interaction as well as the ability to induce
      filopodia. Similarly, the Verprolin (V)-domain of WIRE is critical for IRSp53
      WIRE interaction and for filopodia formation. The interaction between WIRE and
      IRSp53 is regulated by Cdc42 as mutations which abolish Cdc42-IRSp53 interaction
      lead to loss of IRSp53-WIRE interaction as shown by pull down assay. The plasma
      membrane localization of IRSp53 is dependent on Cdc42 and WIRE. Expression of
      Cdc42(G12V) (active mutant) with WIRE-IRSp53 caused significant increase in the
      number of filopodia per cell. Thus our results show that Cdc42 regulates the
      activity of IRSp53 by regulating the IRSp53-WIRE interaction as well as
      localization of the complex to plasma membrane to generate filopodia.

PMID- 20678499
TI  - Influence of cell and collagen concentration on the cell-matrix mechanical
      relationship in a corneal stroma wound healing model.
AB  - The effect of different collagen and cell concentrations on the mechanical and
      remodeling behaviors of corneal stroma wound healing models consisting of
      collagen hydrogels seeded with human corneal fibroblasts during a 25 day culture
      period were examined. Human corneal fibroblasts were seeded at 1 * 10(5), 3 *
      10(5) or 5 * 10(5) cells per hydrogel, and collagen concentrations of 2.5 mg/ml,
      3.5 mg/ml or 4.5 mg/ml were examined. Two non-destructive techniques, spherical
      indentation and optical coherence tomography, were used to measure the elastic
      modulus and dimensional changes respectively at several time-points over the
      culture period. The elastic modulus of the hydrogels increased continuously over
      25 days. Hydrogels with higher initial cell seeding densities and lower initial
      collagen concentrations were found to increase in elastic modulus faster and
      possessed a higher elastic modulus by the end of the culture period when compared
      to the other hydrogels. A mathematical equation was applied to accurately fit the
      change in elastic modulus over time. This study demonstrates a robust in vitro
      technique able to monitor the effect of different parameters on the cell-matrix
      mechanical relationship in a corneal stroma model during prolonged culture
      periods and enhances our understanding on corneal wound healing processes.

PMID- 20678497
TI  - Left-right patterning in the mouse requires Epb4.1l5-dependent morphogenesis of
      the node and midline.
AB  - The mouse node is a transient early embryonic structure that is required for left
      right asymmetry and for generation of the axial midline, which patterns neural
      and mesodermal tissues. The node is a shallow teardrop-shaped pit that sits at
      the distal tip of the early headfold (e7.75) embryo. The shape of the node is
      believed to be important for generation of the coherent leftward fluid flow
      required for initiation of left-right asymmetry, but little is known about the
      morphogenesis of the node. Here we show that the FERM domain protein
      Lulu/Epb4.1l5 is required for left-right asymmetry in the early mouse embryo.
      Unlike other genes previously shown to be required for left-right asymmetry in
      the mouse, lulu is not required for specification of node cell identity, for
      Nodal signaling in the node or for ciliogenesis. Instead, lulu is required for
      proper morphogenesis of the node and midline. The precursors of the wild-type
      node undergo a series of rapid morphological transitions. First, node precursors
      arise from an epithelial-to-mesenchymal transition at the anterior primitive
      streak. While in the mesenchymal layer, the node precursors form several ciliated
      rosette-like clusters; they then rapidly undergo a mesenchymal-to-epithelial
      transition to insert into the outer, endodermal layer of the embryo. In lulu
      mutants, node precursor cells are specified and form clusters, but those clusters
      fail to coalesce to make a single continuous node epithelium. The data suggest
      that the assembly of the contiguous node epithelium from mesenchymal clusters
      requires a rapid reorganization of apical-basal polarity that depends on
      Lulu/Epb4.1l5.

PMID- 20678500
TI  - T3 fails to restore mitochondrial thiol redox status altered by experimental
      hypothyroidism in rat testis.
AB  - Oxidative stress impaired sperm function might lead to infertility. The objective
      of this study was to evaluate the effects of altered thyroid hormone levels on
      regulation of mitochondrial glutathione redox status and its dependent
      antioxidant defense system in adult rat testis and their correlation with
      testicular function. Adult male Wistar rats were rendered hypothyroid by
      administration of 6-n-propyl-2-thiouracil in drinking water for six weeks. At the
      end of the treatment period, a subset of the hypothyroid rats was treated with
      T(3) (20 MUg/100g body weight/day for 3 days). Mitochondria were isolated from
      euthyroid, hypothyroid and hypothyroid+T(3)-treated rat testes, and sub
      fractionated into sub-mitochondrial particles and matrix fractions. Mitochondrial
      respiration, oxidative stress indices and antioxidant defenses were assayed. The
      results were correlated with daily testicular sperm production and epididymal
      sperm viability. Increased pro-oxidant level and reduced antioxidant capacity
      rendered the hypothyroid mitochondria susceptible to oxidative injury. The extent
      of damage was more evident in the membrane fraction. This was reflected in higher
      degree of oxidative damages inflicted upon membrane lipids and proteins. While
      membrane proteins were more susceptible to carbonylation, thiol residue damage
      was evident in matrix fraction. Reduced levels of glutathione and ascorbate
      further weakened the antioxidant defenses and impaired testicular function.
      Hypothyroid condition disturbed intra-mitochondrial thiol redox status leading to
      testicular dysfunction. Hypothyroidism-induced oxidative stress condition could
      not be reversed with T(3) treatment.

PMID- 20678501
TI  - Urate is a ligand for the transcriptional regulator PecS.
AB  - PecS is a member of the MarR (multiple antibiotic resistance regulator) family,
      which has been shown in Erwinia to regulate the expression of virulence genes.
      MarR homologs typically bind a small molecule ligand, resulting in attenuated DNA
      binding. For PecS, the natural ligand has not been identified. We have previously
      shown that urate is a ligand for the Deinococcus radiodurans-encoded MarR homolog
      HucR (hypothetical uricase regulator) and identified residues responsible for
      ligand binding. We show here that all four residues involved in urate binding and
      propagation of conformational changes to DNA recognition helices are conserved in
      PecS homologs, suggesting that urate is the ligand for PecS. Consistent with this
      prediction, Agrobacterium tumefaciens PecS specifically binds urate, and urate
      attenuates DNA binding in vitro. PecS binds two operator sites in the intergenic
      region between the divergent pecS gene and pecM genes, one of which features two
      partially overlapping repeats to which PecS binds as a dimer on opposite faces of
      the duplex. Notably, urate dissociates PecS from cognate DNA, allowing
      transcription of both genes in vivo. Taken together, our data show that urate is
      a ligand for PecS and suggest that urate serves a novel function in signaling the
      colonization of a host plant.

PMID- 20678502
TI  - Conformational changes and ligand recognition of Escherichia coli D-xylose
      binding protein revealed.
AB  - ATP binding cassette transport systems account for most import of necessary
      nutrients in bacteria. The periplasmic binding component (or an equivalent
      membrane-anchored protein) is critical to recognizing cognate ligand and
      directing it to the appropriate membrane permease. Here we report the X-ray
      structures of D-xylose binding protein from Escherichia coli in ligand-free open
      form, ligand-bound open form, and ligand-bound closed form at 2.15 A, 2.2 A, and
      2.2 A resolutions, respectively. The ligand-bound open form is the first such
      structure to be reported at high resolution; the combination of the three
      different forms from the same protein furthermore gives unprecedented details
      concerning the conformational changes involved in binding protein function. As is
      typical of the structural family, the protein has two similar globular domains,
      which are connected by a three-stranded hinge region. The open liganded structure
      shows that xylose binds first to the C-terminal domain, with only very small
      conformational changes resulting. After a 34 degrees  closing motion, additional
      interactions are formed with the N-terminal domain; changes in this domain are
      larger and serve to make the structure more ordered near the ligand. An analysis
      of the interactions suggests why xylose is the preferred ligand. Furthermore, a
      comparison with the most closely related proteins in the structural family shows
      that the conformational changes are distinct in each type of binding protein,
      which may have implications for how the individual proteins act in concert with
      their respective membrane permeases.

PMID- 20678504
TI  - A large population parental care game: polymorphisms and feedback between
      patterns of care and the operational sex ratio.
AB  - This article presents a game theoretic model of parental care which models the
      feedback between patterns of care and the operational sex ratio. It is assumed
      here that males can be in one of two states: searching for a mate or breeding
      (including caring for their offspring). Females can be in one of three states:
      receptive (searching), non-receptive or breeding. However, these sets of states
      can be adapted to the physiology of a particular species. The length of time that
      an individual remains in the breeding state depends on the level of care an
      individual gives. When in the searching state, individuals find partners at a
      rate dependent on the proportion of members of the opposite sex searching. These
      rates are defined to satisfy the Fisher condition that the total number of
      offspring of males equals the total number of offspring of females. The
      operational sex ratio is not defined exogenously, but can be derived from the
      adult sex ratio and the pattern of parental care. Pure strategy profiles and so
      called single sex stable polymorphisms, in which behaviour is varied within one
      sex, are derived analytically. The difference between mixed evolutionarily stable
      strategies and stable polymorphisms within this framework is highlighted. The
      effects of various physiological and demographic parameters on patterns of care
      are considered.

PMID- 20678505
TI  - On the proportion of cancer stem cells in a tumour.
AB  - It is now generally accepted that cancers contain a sub-population, the cancer
      stem cells (CSCs), which initiate and drive a tumour's growth. At least until
      recently it has been widely assumed that only a small proportion of the cells in
      a tumour are CSCs. Here we use a mathematical model, supported by experimental
      evidence, to show that such an assumption is unwarranted. We show that CSCs may
      comprise any possible proportion of the tumour, and that the higher the
      proportion the more aggressive the tumour is likely to be.

PMID- 20678503
TI  - The miR-15/107 group of microRNA genes: evolutionary biology, cellular functions,
      and roles in human diseases.
AB  - The miR-15/107 group of microRNA (miRNA) gene is increasingly appreciated to
      serve key functions in humans. These miRNAs regulate gene expression involved in
      cell division, metabolism, stress response, and angiogenesis in vertebrate
      species. The miR-15/107 group has also been implicated in human cancers,
      cardiovascular disease and neurodegenerative disease, including Alzheimer's
      disease. Here we provide an overview of the following: (1) the evolution of miR
      15/107 group member genes; (2) the expression levels of miRNAs in mammalian
      tissues; (3) evidence for overlapping gene-regulatory functions by different
      miRNAs; (4) the normal biochemical pathways regulated by miR-15/107 group miRNAs;
      and (5) the roles played by these miRNAs in human diseases. Membership in this
      group is defined based on sequence similarity near the mature miRNAs' 5' end: all
      include the sequence AGCAGC. Phylogeny of this group of miRNAs is incomplete;
      thus, a definitive taxonomic classification (e.g., designation as a
      "superfamily") is currently not possible. While all vertebrates studied to date
      express miR-15a, miR-15b, miR-16, miR-103, and miR-107, mammals alone are known
      to express miR-195, miR-424, miR-497, miR-503, and miR-646. Multiple different
      miRNAs in the miR-15/107 group are expressed at moderate to high levels in human
      tissues. We present data on the expression of all known miR-15/107 group members
      in human cerebral cortical gray matter and white matter using new miRNA profiling
      microarrays. There is extensive overlap in the mRNAs targeted by miR-15/107 group
      members. We show new data from cultured H4 cancer cells that demonstrate
      similarities in mRNAs targeted by miR-16 and miR-103 and also support the
      importance of the mature miRNAs' 5' seed region in mRNA target recognition. In
      conclusion, the miR-15/107 group of miRNA genes is a fascinating topic of study
      for evolutionary biologists, miRNA biochemists, and clinically oriented
      translational researchers alike.

PMID- 20678506
TI  - A multiscale, spatially distributed model of asthmatic airway hyper
      responsiveness.
AB  - We present a multiscale, spatially distributed model of lung and airway behaviour
      with the goal of furthering the understanding of airway hyper-responsiveness and
      asthma. The model provides an initial computational framework for linking events
      at the cellular and molecular levels, such as Ca(2+) and crossbridge dynamics, to
      events at the level of the entire organ. At the organ level, parenchymal tissue
      is modelled using a continuum approach as a compressible, hyperelastic material
      in three dimensions, with expansion and recoil of lung tissue due to tidal
      breathing. The governing equations of finite elasticity deformation are solved
      using a finite element method. The airway tree is embedded in this tissue, where
      each airway is modelled with its own airway wall, smooth muscle and surrounding
      parenchyma. The tissue model is then linked to models of the crossbridge
      mechanics and their control by Ca(2+) dynamics, thus providing a link to
      molecular and cellular mechanisms in airway smooth muscle cells. By incorporating
      and coupling the models at these scales, we obtain a detailed, computational
      multiscale model incorporating important physiological phenomena associated with
      asthma.

PMID- 20678507
TI  - Testing for neglect in right-hemispheric stroke patients using a new assessment
      battery based upon standardized activities of daily living (ADL).
AB  - Spatial neglect is most frequently observed after right-hemispheric stroke and is
      characterized by a failure to report, to respond, or to orient to stimuli
      presented to the contralesional side. Although many neglect patients show
      difficulties in accomplishing activities of daily living (ADL), to date the
      clinical assessment of neglect is based upon neuropsychological paper-and-pencil
      tests. Thus, essential information about the patient's functional status may be
      missed out. Accordingly, we aimed at developing a new neglect test battery that
      incorporates standardized ADL. Six conventional paper-and-pencil neglect tests
      and eight standardized ADL with newly developed neglect-specific scoring criteria
      and cut-off scores were administered to 68 right-hemispheric stroke patients.
      According to the neuropsychological tests 22 patients showed symptoms suggesting
      neglect, whereas 17 patients showed symptoms suggesting neglect according to the
      newly developed neglect test based upon ADL. Neglect-specific impairments in the
      neuropsychological tests were significantly associated with those in the ADL
      based tests, although dissociations were observed in seven patients. Neglect
      severity (as reflected in the percentage of positive subtests) was comparable for
      both test batteries and both test instruments showed high interrater reliability.
      Voxel-based lesion-symptom mapping revealed that the severity of neglect
      according to the neuropsychological and ADL-based tests was significantly
      associated with lesions within right fronto-parietal networks. We conclude that
      the newly developed ADL-based neglect battery provides an economic and
      ecologically valid tool for the assessment of neglect. The test can be used to
      assess and quantify neglect in everyday activities, and thus to monitor
      realistically rehabilitative needs of neglect patients.

PMID- 20678508
TI  - Frontal subregions mediating Elevator Counting task performance.
AB  - Deficits in sustained attention may lead to action slips in everyday life as
      irrelevant action sequences are inappropriately triggered internally or by the
      environment. While deficits in sustained attention have been associated with
      damage to the frontal lobes of the brain, little is known about the role of the
      frontal lobes in the Elevator Counting subtest of the Test of Everyday Attention.
      In the current study, 55 frontal patients subdivided into medial, orbital and
      lateral subgroups, 18 patients with posterior lesions and 82 healthy controls
      performed the Elevator Counting task. The results revealed that patients with
      medial and left lateral prefrontal lesions were significantly impaired on the
      task compared to healthy controls. Research suggests that patients with medial
      lesions are susceptible to competition from task irrelevant schema; whereas the
      left lateral group in the current study may fail to keep track of the tones
      already presented.

PMID- 20678509
TI  - Parieto-occipital suppression eliminates implicit bidirectionality in grapheme
      colour synaesthesia.
AB  - Synaesthesia is a condition in which the input of one sensory modality triggers
      extraordinary additional experiences. On an explicit level, subjects affected by
      this condition normally report unidirectional experiences. In grapheme-colour
      synaesthesia for example, the letter A printed in black may trigger a red colour
      experience but not vice versa. However on an implicit level, at least for some
      types of synaesthesia, bidirectional activation is possible. In this study we
      tested whether bidirectional implicit activation is mediated by the same brain
      areas as explicit synaesthetic experiences. Specifically, we demonstrated
      suppression of implicit bidirectional activation with the application of
      transcranial magnetic stimulation over parieto-occipital brain areas. Our
      findings indicate that parieto-occipital regions are not only involved in
      explicit but also implicit synaesthetic binding.

PMID- 20678510
TI  - Effects of parietal TMS on somatosensory judgments challenge interhemispheric
      rivalry accounts.
AB  - Interplay between the cerebral hemispheres is vital for coordinating perception
      and behavior. One influential account holds that the hemispheres engage in
      rivalry, each inhibiting the other. In the somatosensory domain, a seminal paper
      claimed to demonstrate such interhemispheric rivalry, reporting improved tactile
      detection sensitivity on the right hand after transcranial magnetic stimulation
      (TMS) to the right parietal lobe (Seyal, Ro, & Rafal, 1995). Such improvement in
      tactile detection ipsilateral to TMS could follow from interhemispheric rivalry,
      if one assumes that TMS disrupted cortical processing under the coil and thereby
      released the other hemisphere from inhibition. Here we extended the study by
      Seyal et al. (1995) to determine the effects of right parietal TMS on tactile
      processing for either hand, rather than only the ipsilateral hand. We performed
      two experiments applying TMS in the context of median-nerve stimulation; one
      experiment required somatosensory detection, the second somatosensory intensity
      discrimination. We found different TMS effects on detection versus
      discrimination, but neither set of results followed the prediction from
      hemispheric rivalry that enhanced performance for one hand should invariably be
      associated with impaired performance for the other hand, and vice-versa. Our
      results argue against a strict rivalry interpretation, instead suggesting that
      parietal TMS can provide a pedestal-like increment in somatosensory response.

PMID- 20678511
TI  - Enhanced fear recall and emotional arousal in rats recovering from chronic
      variable stress.
AB  - Emergence of posttraumatic-like behaviors following chronic trauma is of interest
      given the rising prevalence of combat-related posttraumatic stress disorder
      (PTSD). Stress associated with combat usually involves chronic traumatization,
      composed of multiple, single episode events occurring in an unpredictable
      fashion. In this study, we investigated whether rats recovering from repeated
      trauma in the form of chronic variable stress (CVS) express posttraumatic stress
      like behaviors and dysregulated neuroendocrine responses. Cohorts of Long-Evans
      rats underwent a 7 day CVS paradigm followed by behavioral and neuroendocrine
      testing during early (16 h post CVS) and delayed (7 day) recovery time points. A
      fear conditioning-extinction-reminder shock paradigm revealed that CVS induces
      exaggerated fear recall to reminder shock, suggestive of potentiated fear memory.
      Rats with CVS experience also expressed a delayed expression of fearful arousal
      under aversive context, however, social anxiety was not affected during post-CVS
      recovery. Persistent sensitization of the hypothalamic-pituitary
      adrenocorticotropic response to a novel acute stressor was observed in CVS
      exposed rats. Collectively, our data are consistent with the constellation of
      symptoms associated with posttraumatic stress syndrome, such as re-experiencing,
      and arousal to fearful contexts. The CVS-recovery paradigm may be useful to
      simulate trauma outcomes following chronic traumatization that is often
      associated with repeated combat stress.

PMID- 20678512
TI  - Epigenetic influences of low-dose bisphenol A in primary human breast epithelial
      cells.
AB  - Substantial evidence indicates that exposure to bisphenol A (BPA) during early
      development may increase breast cancer risk later in life. The changes may
      persist into puberty and adulthood, suggesting an epigenetic process being
      imposed in differentiated breast epithelial cells. The molecular mechanisms by
      which early memory of BPA exposure is imprinted in breast progenitor cells and
      then passed onto their epithelial progeny are not well understood. The aim of
      this study was to examine epigenetic changes in breast epithelial cells treated
      with low-dose BPA. We also investigated the effect of BPA on the ERalpha
      signaling pathway and global gene expression profiles. Compared to control cells,
      nuclear internalization of ERalpha was observed in epithelial cells preexposed to
      BPA. We identified 170 genes with similar expression changes in response to BPA.
      Functional analysis confirms that gene suppression was mediated in part through
      an ERalpha-dependent pathway. As a result of exposure to BPA or other estrogen
      like chemicals, the expression of lysosomal-associated membrane protein 3 (LAMP3)
      became epigenetically silenced in breast epithelial cells. Furthermore, increased
      DNA methylation in the LAMP3 CpG island was this repressive mark preferentially
      occurred in ERalpha-positive breast tumors. These results suggest that the in
      vitro system developed in our laboratory is a valuable tool for exposure studies
      of BPA and other xenoestrogens in human cells. Individual and geographical
      differences may contribute to altered patterns of gene expression and DNA
      methylation in susceptible loci. Combination of our exposure model with
      epigenetic analysis and other biochemical assays can give insight into the
      heritable effect of low-dose BPA in human cells.

PMID- 20678513
TI  - Exposure to acrolein by inhalation causes platelet activation.
AB  - Acrolein is a common air pollutant that is present in high concentrations in
      wood, cotton, and tobacco smoke, automobile exhaust and industrial waste and
      emissions. Exposure to acrolein containing environmental pollutants such as
      tobacco smoke and automobile exhaust has been linked to the activation of the
      coagulation and hemostasis pathways and thereby to the predisposition of
      thrombotic events in human. To examine the effects of acrolein on platelets,
      adult male C57Bl/6 mice were subjected acute (5ppm for 6h) or sub-chronic (1ppm,
      6h/day for 4days) acrolein inhalation exposures. The acute exposure to acrolein
      did not cause pulmonary inflammation and oxidative stress, dyslipidemia or induce
      liver damage or muscle injury. Platelet GSH levels in acrolein-exposed mice were
      comparable to controls, but acrolein-exposure increased the abundance of protein
      acrolein adducts in platelets. Platelets isolated from mice, exposed to both
      acute and sub-chronic acrolein levels, showed increased ADP-induced platelet
      aggregation. Exposure to acrolein also led to an increase in the indices of
      platelet activation such as the formation of platelet-leukocyte aggregates in the
      blood, plasma PF4 levels, and increased platelet-fibrinogen binding. The bleeding
      time was decreased in acrolein exposed mice. Plasma levels of PF4 were also
      increased in mice exposed to environmental tobacco smoke. Similar to inhalation
      exposure, acrolein feeding to mice also increased platelet activation and
      established a pro-thrombotic state in mice. Together, our data suggest that
      acrolein is an important contributing factor to the pro-thrombotic risk in human
      exposure to pollutants such as tobacco smoke or automobile exhaust, or through
      dietary consumption.

PMID- 20678514
TI  - Selective enhancement of fentanyl-induced antinociception by the delta agonist
      SNC162 but not by ketamine in rhesus monkeys: Further evidence supportive of
      delta agonists as candidate adjuncts to mu opioid analgesics.
AB  - Mu-opioid receptor agonists such as fentanyl are effective analgesics, but their
      clinical use is limited by untoward effects. Adjunct medications may improve the
      effectiveness and/or safety of opioid analgesics. This study compared
      interactions between fentanyl and either the noncompetitive N-methyl-D-aspartate
      (NMDA) glutamate receptor antagonist ketamine or the delta-opioid receptor
      agonist SNC162 [(+)-4-[(alphaR)-alpha-[(2S,5R)-2,5-dimethyl-4-(2-propenyl)-1
      piperazinyl]-(3-phenyl)methyl]-N,N-diethylbenzamide] in two behavioral assays in
      rhesus monkeys. An assay of thermal nociception evaluated tail-withdrawal
      latencies from water heated to 50 and 54 degrees C. An assay of schedule
      controlled responding evaluated response rates maintained under a fixed-ratio 30
      schedule of food presentation. Effects of each drug alone and of three mixtures
      of ketamine+fentanyl (22:1, 65:1, 195:1 ketamine/fentanyl) or SNC162+fentanyl
      (59:1, 176:1, 528:1 SNC162/fentanyl) were evaluated in each assay. All drugs and
      mixtures dose-dependently decreased rates of food-maintained responding, and drug
      proportions in the mixtures were based on relative potencies in this assay.
      Ketamine and SNC162 were inactive in the assay of thermal antinociception, but
      fentanyl and all mixtures produced dose-dependent antinociception. Drug
      interactions were evaluated using dose-addition and dose-ratio analysis. Dose
      addition analysis revealed that interactions for all ketamine/fentanyl mixtures
      were additive in both assays. SNC162/fentanyl interactions were usually additive,
      but one mixture (176:1) produced synergistic antinociception at 50 degrees C.
      Dose-ratio analysis indicated that ketamine failed to improve the relative
      potency of fentanyl to produce antinociception vs. rate suppression, whereas two
      SNC162/fentanyl mixtures (59:1 and 176:1) increased the relative potency of
      fentanyl to produce antinociception. These results suggest that delta agonists
      may produce more selective enhancement than ketamine of mu agonist-induced
      antinociception.

PMID- 20678515
TI  - KST5468, a new T-type calcium channel antagonist, has an antinociceptive effect
      on inflammatory and neuropathic pain models.
AB  - The T-type Ca(2+) channel is a low-voltage-activated Ca(2+) channel related to
      nociceptive stimuli. Increases in Ca(2+) due to calcium channel activation
      enhance pain sensitivity through both peripheral and central pain pathways. We
      have developed a novel compound, KST5468, which is a T-type calcium channel
      antagonist. The new synthetic compound may have an antinociceptive effect, and
      thus we evaluated KST5468 as a putative analgesic in a hot plate test, a formalin
      test, and two neuropathic pain models. KST5468 caused a significant increase in
      latency in the hot plate test at 30min after a 10mg/kg peritoneal injection of
      the compound. Interestingly, in the second phase of formalin test, KST5468
      decreased pain behaviors in a dose-dependent manner. Moreover, in two neuropathic
      pain models induced by chronic constriction and spared nerve injury, KST5468
      significantly increased the mechanical pain threshold. Using
      immunohistochemistry, expression of two well known pain-related molecular
      markers, c-Fos and calcitonin gene-related peptide (CGRP), and phosphorylated
      extracellular signal-related kinase (p-ERK) were found to be decreased in the
      laminae I-II layers of the ipsilateral L4-L5 spinal dorsal horn in KST5468
      treated mice. Taken together, the results of this study suggest that KST5468 may
      be an effective antinociceptive agent for neuropathic pain.

PMID- 20678516
TI  - Pharmacological evaluation of a novel assay for detecting glycine transporter 1
      inhibitors and their antipsychotic potential.
AB  - Multiple lines of evidence support the notion that hypofunction of glutamatergic
      neurotransmission is involved in the pathophysiology of schizophrenia. Moreover,
      glycine and glycine modulators have beneficial effects in patients with
      schizophrenia, particularly when added on to existing therapy. As glycine is an
      obligatory co-agonist at the NR1 subunit of the NMDA receptor, blockade of
      glycine uptake at the glycine transporter type-1 (GlyT1) can enhance low
      glutamatergic tone. L-687,414 is an antagonist at the glycine modulatory site of
      the NMDA complex and, behaviorally, increases locomotion. A series of GlyT1
      inhibitors along with other psychoactive compounds were examined for their
      ability to enhance or inhibit the action of L-687,414. GlyT1 inhibitors and the
      other compounds were examined initially for effects on [(3)H]-glycine uptake in
      CHO cells expressing hGlyT1b cDNA and for their ability to displace the NMDA
      glycine site ligand [(3)H]-L-689,560 from isolated rat forebrain membrane
      preparations. The in vivo activity of these compounds was determined in mice by
      measuring their ability to prevent L-687,414-induced hyperlocomotion. GlyT1
      inhibitors blocked [(3)H]-glycine uptake in cells expressing the human
      transporter; other compounds had little or no activity. None of the compounds had
      affinity for the glycine site of the NMDA receptor complex. Hyperlocomotion
      induced by L-687,414 was dose-dependently reduced by GlyT1 inhibitors and
      antipsychotic drugs but not by morphine, fluoxetine or a moderate dose of
      diazepam. Therefore, this behavioral approach can reliably detect GlyT1
      inhibitors which, in turn, may have some activity in common with drugs having
      antipsychotic effects.

PMID- 20678517
TI  - Neuroprotective effect of Bacopa monniera on ischemia induced brain injury.
AB  - PURPOSE: Brain stroke is a leading cause of death without effective treatment. B.
      monniera, an Indian herbal medicine, exerts antioxidant activity and antistress
      activity by modulating the antioxidative defence system. We wanted to test if B.
      monniera could alleviate the ischemia induced brain injury and cognitive
      dysfunction in Wistar rats. PROCEDURE: We studied the effect of B. monniera
      (120mg kg(-1), 160mg kg(-1) and 240mg kg(-1) P.O.) on transient intracarotid
      artery (ICA) occlusion induced ischemia by testing the neurobehavioral and
      biochemical parameters on treated and control rats. FINDINGS: B. monniera
      attenuated the reduced transfer latency in ischemic rats in a step through test
      and showed a protective effect on ischemia induced memory impairment in the plus
      maze task. It also showed a marginal improvement in neurodeficit score and fore
      limb muscle grip strength. B. monniera reduced the infarct size in the ischemic
      brain. It also decreased nitrite, nitrate and lipid peroxidation and
      significantly improved catalase activity. CONCLUSION: These observations suggest
      the neuroprotective and antioxidant activity of B. monniera on ischemia induced
      brain injury and pave the way for future investigations.

PMID- 20678518
TI  - Interpenetrating network hydrogel membranes of sodium alginate and poly(vinyl
      alcohol) for controlled release of prazosin hydrochloride through skin.
AB  - Interpenetrating network (IPN) hydrogel membranes of sodium alginate (SA) and
      poly(vinyl alcohol) (PVA) were prepared by solvent casting method for transdermal
      delivery of an anti-hypertensive drug, prazosin hydrochloride. The prepared
      membranes were thin, flexible and smooth. The X-ray diffraction studies indicated
      the amorphous dispersion of drug in the membranes. Differential scanning
      calorimetric analysis confirmed the IPN formation and suggests that the membrane
      stiffness increases with increased concentration of glutaraldehyde (GA) in the
      membranes. All the membranes were permeable to water vapors depending upon the
      extent of cross-linking. The in vitro drug release study was performed through
      excised rat abdominal skin; drug release depends on the concentrations of GA in
      membranes. The IPN membranes extended drug release up to 24 h, while SA and PVA
      membranes discharged the drug quickly. The primary skin irritation and skin
      histopathology study indicated that the prepared IPN membranes were less irritant
      and safe for skin application.

PMID- 20678519
TI  - Composition analysis and anti-hypoxia activity of polysaccharide from Brassica
      rapa L.
AB  - Crude water-soluble polysaccharides (BRP) were extracted from the root of
      Brassica rapa L. using boiling-water. The polysaccharides were successively
      purified by chromatography on DEAE-cellulose and Sephadex G-100 column, giving
      three major polysaccharide fractions termed BRP1-1, BRP2-1, BRP3-1. The gel
      permeation chromatography (GPC) analysis showed that the average molecular weight
      (Mw) of polysaccharides (BRP1-1, BRP2-1, BRP3-1) were approximately 5.53*10(3)
      Da, 3.35*10(4) Da and 3.37*10(4) Da, respectively. Monosaccharide components
      analysis indicated that BRP1-1 was composed of arabinose and glucose in a molar
      ratio of 1.66:98.34. BRP2-1 was composed of arabinose, galactose and glucose in a
      molar ratio of 9.3:14.63:76.07. BRP3-1 was composed of arabinose, rhamnose,
      galactose and glucose in a molar ratio of 24.98:24.10:44.09:6.83. The evaluation
      of anti-hypoxia activity in vivo revealed that BRP is a novel potential anti
      hypoxia agent.

PMID- 20678520
TI  - Sugar compositions, alpha-glucosidase inhibitory and amylase inhibitory
      activities of polysaccharides from leaves and flowers of Camellia sinensis
      obtained by different extraction methods.
AB  - The sugar compositions, alpha-glucosidase inhibitory and alpha-amylase inhibitory
      activities of polysaccharides from leaves and flowers of green tea (Camellia
      sinensis) obtained by hot water extraction (HWE), boiled water extraction (BWE)
      and enzymatic extraction (EE) were investigated. The yields, sugar contents and
      monosaccharide compositions of tea leaves polysaccharides (TLPS) and tea flower
      polysaccharides (TFPS) were all significantly affected by extraction methods. The
      contents of acidic polysaccharides (APS) extracted by BWE and EE were both much
      more than those by HWE. The yields of TLPS and TFPS were determined as
      EE>BWE>HWE. Enzyme and higher temperature could improve the contents of APS and
      yields of TLPS and TFPS. TLPS and TFPS were all mainly composed of Rha, Ara, Gal,
      Glu and GalA, very little molar contents of GluA, Xyl and Man. It seemed that
      enzyme extraction could be more conducive to increase the content of Ara, Gal and
      GaLA. The molecular weights of TFPS were larger than those of TLPS. The molecular
      weights of polysaccharides obtained by EE decreased. Proteins in tea leaves and
      tea flowers might be decomposed by EE by observing UV peaks and IR absorption.
      peaks. The alpha-glucosidase inhibitory and amylase inhibitory activities of TLPS
      and TFPS obtained by EE were lower than those by water extracted method. The
      inhibitory percentages of TLPS and TFPS against alpha-amylase were all lower than
      alpha-glucosidase for different extractions.

PMID- 20678521
TI  - Assessing the reliability to detect cerebral hypometabolism in probable
      Alzheimer's disease and amnestic mild cognitive impairment.
AB  - Fluorodeoxyglucose positron emission tomography (FDG-PET) studies report
      characteristic patterns of cerebral hypometabolism in probable Alzheimer's
      disease (pAD) and amnestic mild cognitive impairment (aMCI). This study aims to
      characterize the consistency of regional hypometabolism in pAD and aMCI patients
      enrolled in the AD neuroimaging initiative (ADNI) using statistical parametric
      mapping (SPM) and bootstrap resampling, and to compare bootstrap-based
      reliability index to the commonly used type-I error approach with or without
      correction for multiple comparisons. Batched SPM5 was run for each of 1000
      bootstrap iterations to compare FDG-PET images from 74 pAD and 142 aMCI patients,
      respectively, to 82 normal controls. Maps of the hypometabolic voxels detected
      for at least a specific percentage of times over the 1000 runs were examined and
      compared to an overlap of the hypometabolic maps obtained from 3 randomly
      partitioned independent sub-datasets. The results from the bootstrap derived
      reliability of regional hypometabolism in the overall data set were similar to
      that observed in each of the three non-overlapping sub-sets using family-wise
      error. Strong but non-linear association was found between the bootstrap-based
      reliability index and the type-I error. For threshold p=0.0005, pAD was
      associated with extensive hypometabolic voxels in the posterior
      cingulate/precuneus and parietotemporal regions with reliability between 90% and
      100%. Bootstrap analysis provides an alternative to the parametric family-wise
      error approach used to examine consistency of hypometabolic brain voxels in pAD
      and aMCI patients. These results provide a foundation for the use of bootstrap
      analysis characterize statistical ROIs or search regions in both cross-sectional
      and longitudinal FDG-PET studies. This approach offers promise in the early
      detection and tracking of AD, the evaluation of AD-modifying treatments, and
      other biologically or clinical important measurements using brain images and
      voxel-based data analysis techniques.

PMID- 20678522
TI  - Microbead electrochemiluminescence immunoassay for detection and identification
      of Venezuelan equine encephalitis virus.
AB  - An electrochemiluminescence (ECL) immunoassay, incorporating chemically
      biotinylated and ruthenylated antibodies down-selected from a panel of monoclonal
      and polyclonal reagents, was developed to detect and identify Venezuelan equine
      encephalitis virus (VEEV). The limit of detection (LOD) of the optimized ECL
      assay was 10(3)pfu/ml VEEV TC-83 virus and 1 ng/ml recombinant (r) VEEV E2
      protein. The LOD of the ECL assay was approximately one log unit lower than that
      of a sandwich enzyme-linked immunosorbent assay (ELISA) incorporating the same
      immunoreagents. Repetition of ECL assays over time and by different operators
      demonstrated that the assay was reproducible (coefficient of variation 4.7-18.5%
      month-to-month; 3.3-8.8% person-to-person). The VEEV ECL assay exhibited no cross
      reactivity with two closely related alphaviruses or with 21 heterologous
      biological agents. A genetically biotinylated recombinant VEEV antibody,
      MA116SBP, was evaluated for utility for detection of rE2; although functional in
      the ECL assay, the LOD was two log units higher (100 ng/ml vs 1 ng/ml) using
      MA116SBP than when chemically biotinylated antibody was used. The ECL assay
      detected VEEV at the lowest LOD (highest sensitivity) hitherto reported in the
      published literature and ECL assay results were generated in ~60 min compared to
      a 6-8h period required for ELISA. Results have demonstrated a sensitive, rapid,
      and fully automated ECL immunoassay for detection and identification of VEEV.

PMID- 20678523
TI  - Detection of major capsid protein of infectious myonecrosis virus in shrimps
      using monoclonal antibodies.
AB  - Infectious myonecrosis virus (IMNV) has been causing a progressive disease in
      farm-reared shrimps in Brazil and Indonesia. Immunodiagnostic methods for IMNV
      detection, although reliable, are not employed currently because monoclonal
      antibodies (MAbs) against this virus are not available. In this study, a fragment
      of the IMNV major capsid protein gene, comprising amino acids 300-527 (IMNV(300
      527)), was cloned and expressed in Escherichia coli. The nucleotide sequence of
      the recombinant IMNV(300-527) fragment displayed a high degree of identity to the
      major capsid protein of IMNV isolates from Brazil (99%) and Indonesia (98%). Ten
      MAbs were generated against the expressed fragment, and eight of these, mostly
      IgG(2a) or IgG(2b), were able to bind to IMNV in tissue extracts from shrimps
      infected naturally in immunodot-blot assays. Six of these MAbs recognized a
      approximately 100 kDa protein in a Western-blot, which is the predicted mass of
      IMNV major capsid protein, and also bound to viral inclusions present in muscle
      fibroses and in coagulative myonecrosis, as demonstrated by immunohistochemistry.
      Among all those MAbs created, four did not cross-react with non-infected shrimp
      tissues; this observation supports their applicability as a sensitive and
      specific immunodiagnosis of IMNV infection in shrimps.

PMID- 20678524
TI  - The effect of denervation of the locus coeruleus projections with N-(2
      chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) on cocaine-induced locomotion and
      place preference in rats.
AB  - The potential contribution of locus coeruleus (LC)-derived noradrenaline (NA) in
      the motor activating and rewarding effects of cocaine (15 mg/kg) were assessed
      following administration of the neurotoxin N-(2-chloroethyl)-N-ethyl-2
      bromobenzylamine (DSP-4). In Experiment 1, administration of 10 mg/kg of DSP-4
      similarly to substantial denervation with 50 mg/kg of DSP-4 significantly
      attenuated the activating effects of cocaine during the first cocaine-paired
      training session (30 min) in the conditioned place preference (CPP) apparatus.
      Only administration of the higher dose (50 mg/kg) of DSP-4 attenuated line
      crossings during the last training, while both doses reduced rearings. Thus, both
      minor and substantial denervation of LC reduced but did not abolish locomotion
      activating effect of cocaine. Cocaine CPP as measured by increment of time spent
      in the previously cocaine-paired chamber during drug-free conditions before and
      after cocaine-paired trainings was clearly revealed only in animals with intact
      projections from the LC, and was entirely absent after a large lesion of LC
      projections by DSP-4 (50 mg/kg). Because recovery of noradrenaline levels by the
      end of experiment did not allow assessment of the efficacy of the neurotoxin, the
      effect of DSP-4 pre-treatment on the acute psychomotor effect of cocaine was re
      examined in an independent experiment (Experiment 2). Near complete denervation
      of the LC projections again reduced the effect of cocaine, but the lower dose of
      DSP-4 had no effect, suggesting that small lesions of the LC do not have a robust
      impact. Overall, this study demonstrates that both unconditioned and conditioned
      effects of cocaine depend upon the integrity of LC projections.

PMID- 20678525
TI  - Loss of learning in mice when exposed to rat odor: a water maze study.
AB  - The study was designed to test the hypothesis if predator stress can affect
      learning in mice when exposed to rat odor. We investigated the spatial memory
      performance of Swiss albino mice in a 7 d Morris water maze (MWM) paradigm by
      exposing them to the odor of predator (Wistar rats). The results revealed that
      rat odor produced amnesia in the mice while mice odor did not affect learning in
      rats, analyzed by the escape latency time (ELT) in acquition trials and search
      error in retrieval trials. Moreover, the memory loss in mice was comparable to
      the degree of amnesia produced by scopolamine, a control amnesic agent.

PMID- 20678526
TI  - Pharmacological inhibition of the lateral habenula improves depressive-like
      behavior in an animal model of treatment resistant depression.
AB  - Identifying new treatment approaches for treatment resistant depression (TRD) is
      an important topic for translational psychiatry. Functional inhibition of the
      lateral habenula (LHb) has recently been claimed to offer such an option for TRD.
      Rats which are bred for high susceptibility to develop learned helplessness
      provide a genetic model for TRD. We used the gamma-aminobutyric acid agonist
      muscimol to inhibit the LHb in Sprague-Dawley rats with congenital learned
      helplessness (cLH). Stereotactic pharmacological inhibition of the LHb exerted
      antidepressive effects in treatment resistant cLH rats.

PMID- 20678527
TI  - Blocking SK channels impairs long-term memory formation in young chicks.
AB  - The role of small-conductance calcium-activated potassium (SK) channels in memory
      formation was explored in chicks trained on a single-trial discrimination
      avoidance task. Blockade of SK channels using apamin (1 nM, 0.02 ng/hem, i.c.)
      impaired long-term memory retention when administered between 10 min prior to,
      and 30 min after, training. Apamin (1 nM, 0.02 ng/hem, immediately post-training,
      i.c.) resulted in persistent impairment of retention during the long-term memory
      stage by 90 min post-training until at least 24 h post-training, indicating SK
      channels contribute to long-term memory.

PMID- 20678528
TI  - Reciprocal interactions between MK-801, sleep deprivation and recovery in
      modulating rat behaviour.
AB  - Increasing evidence indicates that sleep deprivation alters behavioural responses
      to various pharmacological agents which might be associated to changes in
      receptor systems. The present work addressed the effects of sleep deprivation and
      recovery on behavioural changes induced by MK-801, and investigated whether such
      effects are related to changes in NMDA receptor (NMDAR) binding. Male Wistar rats
      were deprived of sleep for 96 h using the platform method (SD group), or were
      sleep deprived and then allowed to recover sleep for 24 h (SR group). Animals
      were treated with saline or 0.05, 0.10 or 0.20 mg/kg MK-801 before testing in an
      open field arena and elevated plus maze. A separate set of animals was sacrificed
      for [3H]MK-801 binding analysis in 40 brain regions. MK-801-induced
      hyperlocomotion was facilitated in a dose-dependent fashion after SR, while SD
      induced increase in grooming was antagonized by the drug. Anxiolytic effects of
      0.05 and 0.10 mg/kg MK-801 were unaffected by SD or SR conditions. No significant
      differences among groups were found in NMDAR binding. These findings indicate
      that the combined effects of MK-801 and sleep deprivation and recovery interact
      in a complex fashion to affect rat behaviour. They further suggest that such
      effects cannot be attributed to altered NMDAR binding in brain.

PMID- 20678529
TI  - Sildenafil counteracts the inhibitory effect of social subordination on
      competitive aggression and sexual motivation in male mice.
AB  - The effects of chronic intra-peritoneal administration of 10 mg/kg (t.i.w., for 5
      weeks) of sildenafil on competitive aggression, sexual behaviour and body weight
      gain was tested in CD1 subordinate male mice in two experimental contexts: 1)
      "low levels of aggression", i.e. housing in dyads of siblings 2) "high levels of
      aggression", i.e. exposure to a model of chronic psychosocial stress with an
      unfamiliar mice. Subordinate mice in both experimental contexts were injected
      with sildenafil or saline. After 2 weeks of sildenafil administration, a subgroup
      of subordinates exposed to "high levels of aggression" began to counterattack
      their dominant counterparts at higher rates than saline-injected subordinates.
      This effect was essentially similar but faster in subordinates subjected to "low
      levels of aggression". As far as sexual behaviour is concerned, in both
      experimental contexts, sildenafil-injected subordinated mice showed significant
      lower latencies to mount a proceptive female when compared to saline-injected
      subjects. Furthermore, in the "high levels of aggression" context, Sildenafil
      reduced stress-induced body weight gain. Sildenafil showed no effects in
      individually housed males serving as controls. In conclusion, chronic Sildenafil
      treatment counteracts the inhibitory effects of social subordination on male
      competitive aggression, sexual behaviour and body weight gain. Overall our data
      suggests that sildenafil could be acting in the central nervous system to
      modulate sexual and agonistic motivation.

PMID- 20678530
TI  - Release of DNA from polyelectrolyte multilayers fabricated using 'charge
      shifting' cationic polymers: tunable temporal control and sequential, multi-agent
      release.
AB  - We report an approach to the design of multilayered polyelectrolyte thin films
      (or 'polyelectrolyte multilayers', PEMs) that can be used to provide tunable
      control over the release of plasmid DNA (or multiple different DNA constructs)
      from film-coated surfaces. Our approach is based upon methods for the layer-by
      layer assembly of DNA-containing thin films, and exploits the properties of a new
      class of cationic 'charge-shifting' polymers (amine functionalized polymers that
      undergo gradual changes in net charge upon side chain ester hydrolysis) to
      provide control over the rates at which these films erode and release DNA. We
      synthesized two 'charge-shifting' polymers (polymers 1 and 2) containing
      different side chain structures by ring-opening reactions of poly(2-alkenyl
      azlactone)s with two different tertiary amine functionalized alcohols (3
      dimethylamino-1-propanol and 2-dimethylaminoethanol, respectively). Subsequent
      characterization revealed large changes in the rates of side chain ester
      hydrolysis for these two polymers; whereas the half-life for the hydrolysis of
      the esters in polymer 1 was ~200 days, the half-life for polymer 2 was ~6 days.
      We demonstrate that these large differences in side chain hydrolysis make
      possible the design of PEMs that erode and promote the surface-mediated release
      of DNA either rapidly (e.g., over ~3 days for films fabricated using polymer 2)
      or slowly (e.g., over ~1 month for films fabricated using polymer 1). We
      demonstrate further that it is possible to design films with release profiles
      that are intermediate to these two extremes by fabricating films using solutions
      containing different mixtures of these two polymers. This approach can thus
      expand the usefulness of these two polymers and achieve a broader range of DNA
      release profiles without the need to synthesize polymers with new structures or
      properties. Finally, we demonstrate that polymers 1 and 2 can be used to
      fabricate multilayered films with hierarchical structures that promote the
      sequential release of two different DNA constructs with separate and distinct
      release profiles (e.g., the release of a first construct over a period of ~3
      days, followed by the sustained release of a second for a period of ~70 days).
      With further development, this approach could contribute to the design of
      functional thin films and surface coatings that provide sophisticated control
      over the timing and the order of the release of two or more DNA constructs (or
      other agents) of interest in a range of biomedical contexts.

PMID- 20678531
TI  - The effects of using a nutrition logo on consumption and product evaluation of a
      sweet pastry.
AB  - Nutrition logos have received a great deal of attention to stimulate people to
      eat a healthier diet. However, very little is known neither about actual
      consumption behavior related to nutrition logos nor about potential compensatory
      eating behaviors due to nutrition logos. The aim of this study was to assess the
      effects of using an existing nutrition logo on consumption and product evaluation
      of a chocolate mousse cake. A cross-over design was applied with two conditions:
      a condition with a logo and a condition without a logo. Participants were females
      recruited in the university community (n = 36, mean age 22.6 +/- 6.3). Data on
      consumption, tastefulness, perceived healthiness, dietary restraint and Body Mass
      Index were collected. No significant differences between conditions were found on
      consumption and tastefulness. The cake was rated as significantly less unhealthy
      in the logo condition. In conclusion, results cannot be extrapolated to other
      products, especially not to products that are perceived as healthy. In this
      study, the use of a nutrition logo did not result in an increased consumption and
      had no effect on the rating of taste of a sweet pastry among females from the
      university community.

PMID- 20678532
TI  - Delay discounting moderates the effect of food reinforcement on energy intake
      among non-obese women.
AB  - Recent theoretical approaches to food intake hypothesize that eating represents a
      balance between reward-driven motivation to eat versus inhibitory executive
      function processes, however this hypothesis remains to be tested. The objective
      of the current study was to test the hypothesis that the motivation to eat,
      operationalized by the relative reinforcing value (RRV) of food, and inhibitory
      processes, assessed by delay discounting (DD), interact to influence energy
      intake in an ad libitum eating task. Female subjects (n = 24) completed a DD of
      money procedure, RRV task, and an ad libitum eating task in counterbalanced
      sessions. RRV of food predicted total energy intake, however the effect of the
      RRV of food on energy intake was moderated by DD. Women higher in DD and RRV of
      food consumed greater total energy, whereas women higher in RRV of food but lower
      in DD consumed less total energy. Our findings support the hypothesis that
      reinforcing value and executive function mediated processes interactively
      influence food consumption.

PMID- 20678533
TI  - Effects of dietary Fusarium mycotoxins on intestinal lymphocyte subset
      populations, cell proliferation and histological changes in avian lymphoid
      organs.
AB  - An experiment was conducted to investigate the effects of dietary Fusarium
      mycotoxins on gut immunity, cell proliferation, and histology of avian lymphoid
      organs. The efficacy of a polymeric glucomannan mycotoxin adsorbent (GMA) was
      also determined. Seventy-two one-day-old male turkey poults were fed corn, wheat,
      and soybean meal-based diets for 21 days. Diets included control grains,
      contaminated grains and contaminated grains +0.2% GMA. The major contaminant was
      deoxynivalenol (3.9 MUg/g) with lesser amounts of zearalenone (0.67-0.75 MUg/g),
      15-acetyl-deoxynivalenol (0.34 MUg/g) and HT-2 toxin (0.078-0.085 MUg/g). T- and
      B-lymphocyte populations and crypt cellular proliferation in duodenum, jejunum,
      ileum and cecal tonsil were measured immunohistochemically on day 14 and 21.
      Histological changes were recorded after 14 and 21 days of feeding. Feeding
      contaminated grains significantly increased the percentage of B-lymphocytes in
      ileum on day 14, and reduced (P<0.05) the percentages of CD8(+)-lymphocytes in
      cecal tonsil on day 21. GMA supplementation prevented these effects. The feeding
      of contaminated diets also caused a reduction (P<0.05) in ileal crypt
      proliferating cells and a significant increase in spleen secondary follicle on
      day 21. It was concluded that the feeding of grains naturally contaminated with
      Fusarium mycotoxins results in adverse effects on gut immunity and mucosal cell
      proliferation.

PMID- 20678534
TI  - Effect of food azo dyes tartrazine and carmoisine on biochemical parameters
      related to renal, hepatic function and oxidative stress biomarkers in young male
      rats.
AB  - Tartrazine and carmoisine are an organic azo dyes widely used in food products,
      drugs and cosmetics. The present study conducted to evaluate the toxic effect of
      these coloring food additives; on renal, hepatic function, lipid profile, blood
      glucose, body-weight gain and biomarkers of oxidative stress in tissue.
      Tartrazine and carmoisine were administered orally in two doses, one low and the
      other high dose for 30 days followed by serum and tissue sample collection for
      determination of ALT, AST, ALP, urea, creatinine, total protein, albumin, lipid
      profile, fasting blood glucose in serum and estimation of GSH, catalase, SOD and
      MDA in liver tissue in male albino rat. Our data showed a significant increase in
      ALT, AST, ALP, urea, creatinine total protein and albumin in serum of rats dosed
      with tartrazine and carmoisine compared to control rats and these significant
      change were more apparent in high doses than low, GSH, SOD and Catalase were
      decreased and MDA increased in tissue homogenate in rats consumed high tartrazine
      and both doses of carmoisine. We concluded that tartrazine and carmoisine affect
      adversely and alter biochemical markers in vital organs e.g. liver and kidney not
      only at higher doses but also at low doses.

PMID- 20678535
TI  - Protective effects of hesperidin against oxidative stress of tert-butyl
      hydroperoxide in human hepatocytes.
AB  - Increasing evidence regarding free radical generating agents and the inflammatory
      process suggest that accumulation of reactive oxygen species (ROS) could involve
      hepatotoxicity. Hesperidin, a naturally occurring flavonoid presents in fruits
      and vegetables, has been reported to exert a wide range of pharmacological
      effects that include antioxidant, anti-inflammatory, antihypercholesterolemic,
      and anticarcinogenic actions. However, the cytoprotection and mechanism of
      hesperidin to neutralize oxidative stress in human hepatic L02 cells remain
      unclear. In this work, we assessed the capability of hesperidin to prevent tert
      butyl hydroperoxide (t-BuOOH)-induced cell damage by augmenting cellular
      antioxidant defense. Hesperidin significantly protected hepatocytes against t
      BuOOH-induced cell cytotoxicity, such as mitochondrial membrane potential (MMP)
      deplete and lactate dehydrogenase (LDH) release. Hesperidin also remarkably
      prevented indicators of oxidative stress, such as the ROS and lipid peroxidation
      level in a dose-dependent manner. Western blot showed that hesperidin facilitated
      ERK/MAPK phosphorylation which appeared to be responsible for nuclear
      translocation of Nrf2, thereby inducing cytoprotective heme oxygenase-1 (HO-1)
      expression. Based on the results described above, it suggested that hesperidin
      has potential as a therapeutic agent in the treatment of oxidative stress-related
      hepatocytes injury and liver dysfunctions.

PMID- 20678536
TI  - A polyacetylene from Gymnaster koraiensis exerts hepatoprotective effects in vivo
      and in vitro.
AB  - In the present study, we isolated a polyacetylene, gymnasterkoreayne B (GKB),
      from Gymnaster koraiensis and investigated the effect of GKB on the protection
      from oxidative stress-induced cytotoxicity through induction of the expression of
      cellular defense enzymes. GKB induced mRNA expression and enzyme activity of
      NAD(P)H:quinone oxidoreductase (NQO1) in vitro and in vivo, and potently
      increased expression of many cellular defense genes including glutathione-S
      transferases, UDP-glucuronosyltransferase, and glutathione reductase (GSR) in
      normal rat liver. The nuclear factor erythroid 2-related factor 2 (Nrf2) which is
      known to induce various antioxidant and cytoprotective genes, and the genes
      containing the antioxidant response element (ARE), including NQO1, hemeoxygenease
      1, GSR were induced by GKB in HepG2 human hepatocarcinoma cells. Pre-treatment of
      the cells with GKB accelerated the production of glutathione and mitigated
      menadione-induced cytotoxicity in HepG2 cells. Taken together, we found that GKB
      was a novel inducer of phase II detoxification enzymes and cellular defense
      enzymes, resulting in protection of the cells from oxidative stress and
      hepatotoxicity through regulation of detoxifying and antioxidant systems.

PMID- 20678537
TI  - Serum and kidney metabolic changes of rat nephrotoxicity induced by Morning Glory
      Seed.
AB  - Previous nephrotoxicology study on Morning Glory Seed (MGS) mainly focused on
      whole animal level, using creatinine and BUN as biochemical indicators to
      evaluate renal function. This work was designed to delineate the comprehensive
      metabolic syndromes of MGS-induced nephrotoxicity. An ultra liquid chromatography
      coupled with mass spectrometry (UPLC/MS) metabonomic approach was employed to
      characterize the metabolic profile of plasma and kidney tissue extract from rats
      treated with MGS at a single nephrotoxic dose of 15 g/kg/day for 14 consecutive
      days. Acquired data were subjected to principal component analysis (PCA) for
      differentiating the model and the control groups. The results indicated that
      certain metabolic pathways, such as lysophosphatidylcholines formation and
      sphingolipids cycle were accelerated, while the phenylalanine level in serum was
      decreased. We believe that metabonomic approach is helpful to further
      understanding and clinical diagnosis of traditional Chinese medicine (TCM)
      induced nephrotoxicity.

PMID- 20678538
TI  - Olive oil stability under deep-frying conditions.
AB  - The suitability of different commercial olive oil categories for domestic frying
      was investigated. Oil samples were taken every 3h of frying and evaluated for
      free acidity, peroxide and p-anisidine values, specific extinction coefficients,
      oxidative stability, fatty acids, vitamin E, beta-carotene and total phenols,
      until the total polar compounds achieved the maximum legal value (25%). All olive
      oils were fried during more time than the commercial vegetable oil blend taken
      for comparison (from 24 to 27 h, against 15 h). The extra-virgin Protected
      Designation of Origin (PDO) olive oil was characterized by reduced levels of
      oxidation and hydrolysis, and superior amounts of minor antioxidant compounds.
      The "olive oil" commercial category behaves similarly, but "Cobrancosa" olive
      oils performance was slightly worse, and clearly different between years,
      highlighting the importance of blending different cultivars. The vegetable oil,
      despite containing significantly higher amounts of vitamin E, was highly
      susceptible to oxidation under frying conditions when compared to all olive oils.
      The results also show that the chemical composition of olive oils, particularly
      the amount of natural antioxidants, are important parameters in their predictive
      behavior along the frying process, but mostly that olive oil is clearly resistant
      to frying conditions, independently to the commercial category chosen.

PMID- 20678539
TI  - Efficient chemoenzymatic oligosaccharide synthesis by reverse phosphorolysis
      using cellobiose phosphorylase and cellodextrin phosphorylase from Clostridium
      thermocellum.
AB  - Inverting cellobiose phosphorylase (CtCBP) and cellodextrin phosphorylase (CtCDP)
      from Clostridium thermocellum ATCC27405 of glycoside hydrolase family 94
      catalysed reverse phosphorolysis to produce cellobiose and cellodextrins in 57%
      and 48% yield from alpha-d-glucose 1-phosphate as donor with glucose and
      cellobiose as acceptor, respectively. Use of alpha-d-glucosyl 1-fluoride as donor
      increased product yields to 98% for CtCBP and 68% for CtCDP. CtCBP showed broad
      acceptor specificity forming beta-glucosyl disaccharides with beta-(1->4)-
      regioselectivity from five monosaccharides as well as branched beta-glucosyl
      trisaccharides with beta-(1->4)-regioselectivity from three (1->6)-linked
      disaccharides. CtCDP showed strict beta-(1->4)-regioselectivity and catalysed
      linear chain extension of the three beta-linked glucosyl disaccharides,
      cellobiose, sophorose, and laminaribiose, whereas 12 tested monosaccharides were
      not acceptors. Structure analysis by NMR and ESI-MS confirmed two beta-glucosyl
      oligosaccharide product series to represent novel compounds, i.e. beta-D
      glucopyranosyl-[(1->4)-beta-D-glucopyranosyl](n)-(1->2)-D-glucopyranose, and beta
      D-glucopyranosyl-[(1->4)-beta-D-glucopyranosyl](n)-(1->3)-D-glucopyranose (n = 1
      7). Multiple sequence alignment together with a modelled CtCBP structure,
      obtained using the crystal structure of Cellvibrio gilvus CBP in complex with
      glucose as a template, indicated differences in the subsite +1 region that elicit
      the distinct acceptor specificities of CtCBP and CtCDP. Thus Glu636 of CtCBP
      recognized the C1 hydroxyl of beta-glucose at subsite +1, while in CtCDP the
      presence of Ala800 conferred more space, which allowed accommodation of C1
      substituted disaccharide acceptors at the corresponding subsites +1 and +2.
      Furthermore, CtCBP has a short Glu496-Thr500 loop that permitted the C6 hydroxyl
      of glucose at subsite +1 to be exposed to solvent, whereas the corresponding
      longer loop Thr637-Lys648 in CtCDP blocks binding of C6-linked disaccharides as
      acceptors at subsite +1. High yields in chemoenzymatic synthesis, a novel
      regioselectivity, and novel oligosaccharides including products of CtCDP
      catalysed oligosaccharide oligomerisation using alpha-d-glucosyl 1-fluoride, all
      together contribute to the formation of an excellent basis for rational
      engineering of CBP and CDP to produce desired oligosaccharides.

PMID- 20678540
TI  - The effect of C-terminal domain deletion on the catalytic activity of Leishmania
      donovani surface proteinase GP63: Role of Ser446 in proteolysis.
AB  - The kinetoplastid protozoan Leishmania encodes major surface glycoprotein GP63, a
      zinc metallo-peptidase (EC.3.4.24.36) expressed both in promastigote and
      amastigote life stages. In the present study, we explored for the first time the
      role of C-terminal domain (CTD) in proteinase activity by serial truncation of
      Leishmania donovani GP63 (LdGP63) from carboxyl terminal end (CTend). Deletion of
      180-211 amino acids from CTend (Delta420 and Delta389) resulted in almost 50%
      loss of catalytic activity against azocasein, casein and gelatin. Moreover, all
      the truncated constructs showed reduced activity towards immunoglobulin (IgG).
      Upon homology modeling, we identified two residues, S446, and F448 in CTD,
      conserved in different Leishmania species, which were positioned 6.8-11A apart
      from the active site. To ascertain the role of S446 and F448 in catalysis, we
      replaced S446 with Ala and Thr, and F448 with Val and Tyr by site-directed
      mutagenesis. The variant enzymes (S446T, F448V, and F448Y) maintained near wild
      type activity, whereas S446A demonstrated 50% loss of catalytic activity towards
      the cleavage of various biological substrates. Kinetic analysis of S446A resulted
      in a 2.6-fold decrease in the affinity, 10-fold decrease in turn-over rates, and
      large increase in transition-state binding energy (1.4kcal/mol) for the quenched
      peptide substrates. These results emphasize the relevance of CTD in the
      proteolytic activity of LdGP63. Fluorescence spectroscopy, and CD analysis
      however, indicated that the reduced activities showed by Delta389 and S446A were
      not due to global changes in the enzyme structures. Indeed, identification of
      S446 and its possible role in the stabilization of transition-state binding
      between enzyme and substrate can be exploited towards understanding of structure
      function relationship of GP63.

PMID- 20678541
TI  - Stability-dependent behavioural and electro-cortical reorganizations during
      intentional switching between bimanual tapping modes.
AB  - This study investigated behavioural and electro-cortical reorganizations
      accompanying intentional switching between two distinct bimanual coordination
      tapping modes (In-phase and Anti-phase) that differ in stability when produced at
      the same movement rate. We expected that switching to a less stable tapping mode
      (In-to-Anti switching) would lead to larger behavioural perturbations and require
      supplementary neural resources than switching to a more stable tapping mode (Anti
      to-In switching). Behavioural results confirmed that the In-to-Anti switching
      lasted longer than the Anti-to-In switching. A general increase in attention
      related neural activity was found at the moment of switching for both conditions.
      Additionally, two condition-dependent EEG reorganizations were observed. First, a
      specific increase in cortico-cortical coherence appeared exclusively during the
      In-to-Anti switching. This result may reflect a strengthening in inter-regional
      communication in order to engage in the subsequent, less stable, tapping mode.
      Second, a decrease in motor-related neural activity (increased beta spectral
      power) was found for the Anti-to-In switching only. The latter effect may reflect
      the interruption of the previous, less stable, tapping mode. Given that previous
      results on spontaneous Anti-to-In switching revealing an inverse pattern of EEG
      reorganization (decreased beta spectral power), present findings give new insight
      on the stability-dependent neural correlates of intentional motor switching.

PMID- 20678542
TI  - Characterization of conditioned medium of cultured bone marrow stromal cells.
AB  - It has been recognized that bone marrow stromal cell (BMSC) transplantation has
      beneficial effects on spinal cord injury in animal models and therapeutic trials.
      It is hypothesized that BMSCs provide microenvironments suitable for axonal
      regeneration and secrete some trophic factors to rescue affected cells from
      degeneration. However, the molecular and cellular mechanisms of the trophic
      factors involved remain unclear. In the present study, we examined the effects of
      trophic factors secreted by rat BMSCs using bioassays involving cultured
      hippocampal neurons. The conditioned medium (CM) as well as non-contact co
      culture of BMSCs promoted neurite outgrowth and suppressed TUNEL-positive cells
      compared to serum-free D-MEM. Protein analyses of the CM by antibody-based
      protein array analysis and ELISA revealed that the CM contained insulin-like
      growth factor (IGF)-1, hepatocyte growth factor (HGF), vascular endothelial
      growth factor (VEGF), and transforming growth factor (TGF)-beta1. DNA microarray
      analysis revealed that neurons highly expressed receptors of IGF-1 and TGF-beta1.
      However, their expression indices remained unchanged even after the CM treatment.
      The individual trophic factors mentioned above or their combinations were less
      effective at promoting neuronal survival and neurite outgrowth than the CM. The
      present study showed that BMSCs secreted various kinds of molecules into the
      culture medium including trophic factors to promote neuronal survival and neurite
      outgrowth. The main trophic factors responsible remain to be elucidated.

PMID- 20678543
TI  - gamma-band oscillations in fronto-central areas during performance of a
      sensorimotor integration task: a qEEG coherence study.
AB  - This study aimed to elucidate electrophysiological and cortical mechanisms
      involved in anticipatory actions when 23 healthy right-handed subjects had to
      catch a free falling object by qEEG gamma-band (30-100 Hz). It is involved in
      cognitive processes, memory, spatial/temporal and proprioceptive factors. Our
      hypothesis is that an increase in gamma coherence in frontal areas will be
      observed during moment preceding ball drop, due to their involvement in
      attention, planning, selection of movements, preparation and voluntary control of
      action and in central areas during moment after ball drop, due to their
      involvement in motor preparation, perception and execution of movement. However,
      through a paired t-test, we found an increase in gamma coherence for F3-F4
      electrode pair during moment preceding ball drop and confirmed our hypothesis for
      C3-C4 electrode pair. We conclude that gamma plays an important role in
      reflecting binding of several brain areas in a complex motor task as observed in
      our results. Moreover, for selection of movements, preparation and voluntary
      control of action, motor preparation, perception and execution of movement, the
      integration of somatosensory and visual information is mandatory.

PMID- 20678544
TI  - Pressure-induced pain: early sign of diabetes-associated impairment of insulin
      production in rats.
AB  - The lack of simple, non-invasive tests for a sub-clinical decline in insulin
      production hampers detection of early-stage type 1 pre-diabetes. Pressure pain
      withdrawal threshold (PPT) is a sensitive index of insulinopenia in diabetic and
      'pre-diabetic' rats, but its ability to detect human insulin insufficiency is not
      known; if predictive, PPT testing of those at risk for diabetes would be
      warranted. To address this question, we used meta-analyses to demonstrate (i) a
      similar relationship between blood glucose and insulin levels in humans and
      diabetic rats and (ii) the predictive value of PPT for insulinopenia in a
      composite group (n=53) of control, streptozotocin (STZ)-diabetic (STZ-HG), and
      normoglycemic (STZ-NG) rats. The frequency distributions of pooled insulin levels
      (ng/ml) consisted of three sub-populations, with peak values of <0.5, 1.5+/-0.05,
      and 3.2+/-0.04. Using the 2.3rd percentile of the sub-population with the highest
      insulin level (2.81 ng/ml) as a cut-off to define insulinopenia, 40 animals (98%
      of STZ and 25% of controls) were identified with compromised insulin production.
      The frequency distribution of pooled PPT values also consisted of three sub
      populations (peaks at 75.9+/-0.6 g, 97+/-0.3 g and 122+/-0.8 g), and when 106 g
      (the 2.3rd percentile of the most pressure-tolerant sub-population) was used as a
      cut-off, PPT measurements identified 92% of STZ-injected rats and 83% of rats
      with insulinopenia, as defined by 2.81 ng/ml insulin cut-off. Assuming similar
      between-species pain mechanisms, these findings support the potential usefulness
      of PPT measurements for detection of early-stage human type 1 diabetes.

PMID- 20678545
TI  - Apolipoprotein epsilon4 and neuropsychological performance in Alzheimer's disease
      and vascular dementia.
AB  - The apolipoprotein (APOE) epsilon4 allele is a genetic risk factor for the
      development of Alzheimer's disease (AD). It has also been associated with
      vascular dementia (VaD) in some but not all studies. Previous studies have
      examined the role of APOE in predicting performance on cognitive tests in both
      demented and non-demented populations. In cognitively intact individuals,
      statistically significant group differences between APOE epsilon4 carriers and
      non-carriers have been demonstrated for several cognitive domains. In AD studies
      of the impact of APOE epsilon4 on cognition have been conflicting while no
      previous study has assessed cognition and impact of APOE epsilon4 in VaD. In this
      study we investigated the impact of APOE epsilon4 on performance in
      neuropsychological tests including information processing speed in patients with
      mild-moderate AD and VaD. We incorporated both computerized and pen and paper
      tests to ensure a sensitive method of assessing cognition. 109 patients
      participated in the study (VaD=41, AD=68). Neurocognitive performance of 44
      epsilon4 present AD patients was compared to 24 epsilon4absent patients and
      performance of 23 epsilon4 present VaD patients was compared to 18 epsilon4
      absent patients. There was evidence that APOE epsilon4 conferred a risk of poorer
      cognitive functioning in both patient groups. In the AD group presence of
      epsilon4 conferred a negative impact on some measures of speed of information
      processing and immediate recall while in the VaD group epsilon4 present patients
      had evidence of poorer accuracy on tasks such as choice reaction time and spatial
      working memory. In AD and VaD groups epsilon4 present patients showed impairment
      in selective attention. These findings provide further support of the negative
      impact of the epsilon4 allele in cognition.

PMID- 20678546
TI  - Two types of ON direction-selective ganglion cells in rabbit retina.
AB  - Direction-selective ganglion cells (DSGCs) respond with robust spiking to image
      motion in a particular direction. Previously, two main types of DSGCs have been
      described in rabbit retina: the ON-OFF DSGCs respond to both increases and
      decreases in illumination, whereas the ON DSGCs respond only to increases in
      illumination. In this study, we show that there are two distinct types of ON
      DSGCs, which can be separated by differences in their receptive-field properties,
      dendritic morphology and tracer-coupling pattern. While both types show robust
      direction-selectivity, one type responds to increases in illumination with
      sustained firing, whereas the other responds with relatively transient firing.
      The two types of ON DSGCs also have distinct dendritic morphologies: the
      sustained cells give rise to shorter and more numerous terminal dendrites, which
      are distributed throughout the dendritic field forming a space-filling lattice.
      In addition, the transient ON DSGCs, but not the sustained ON DSGCs, show tracer
      coupling to a mosaic of amacrine cells when filled with Neurobiotin. Both types
      of ON DSGCs have been encountered in previous studies but were not recognized as
      distinct types. We propose that the two types also differ in their central
      projections, with only the sustained cells projecting to the medial terminal
      nucleus (MTN) of the accessory optic system (AOS).

PMID- 20678547
TI  - Chondroitin sulfate demarcates astrocytic territories in the mammalian cerebral
      cortex.
AB  - Adjacent astrocytes in the grey matter of the mammalian cerebral cortex are
      organized in a tile-like manner and separated from one another, forming discrete
      domains named "non-overlapping territories". We have previously reported that an
      anti-chondroitin sulfate (CS) antibody, CS-56, marks a subpopulation of cortical
      astrocytes which we named the dandelion clock-like structure (DACS) based on its
      morphological characteristics. In the present study, we found that another anti
      CS antibody (anti-CS-C) was also able to detect the DACS and the morphological
      analysis revealed that a single DACS enwrapped five to six neuronal somata on
      average, which indicated that DACS coincided with a single astrocyte territory.
      Double labeling of CS-C and glial fibrillary acidic protein (GFAP) showed a
      slight overlap between the two territories in the adult cerebral cortex of mice.
      The neuron number enwrapped by a single DACS was unchanged between 3- and 7-week
      old mice, while more extensive processes of DACSs were found in 7-week-old mice
      compared with those in 3-week-old ones. Moreover, the measurement of a single
      DACS area was significantly increased by 45% between 3- and 7-week-old mice. In
      addition, DACSs were found in human, monkey, and domestic pig brains, but not
      mallard ones, indicating that DACS was conserved in mammalian species. Taken
      together, CS demarcates territories of a certain population of cortical
      astrocytes and the cerebral cortex is composed of CS-rich astrocytes and -poor
      astrocytes in a mosaic fashion.

PMID- 20678548
TI  - Intimate associations between the neuropeptide Y system and the galanin
      immunoreactive neurons in the human diencephalon.
AB  - Galanin and neuropeptide Y (NPY) are among the most abundant neuropeptides in the
      hypothalamus. The role of NPY and galanin in the regulation of the secretory
      activity of the anterior pituitary has been well established. In addition, the
      two peptides interact with a number of neurons synthesizing the releasing and
      inhibiting hormones and a large number of other neuropeptides. The aim of the
      present studies was to explore if, as in rodents, NPY innervates galanin
      immunoreactive (IR) neurons in the human diencephalon. Due to the long post
      mortem period and subsequent lack of optimal preservation of the cell membranes
      in the brain, electron microscopy could not be employed to show the presence of
      NPY-IR synapses on galanin-IR neurons. Therefore, we used light microscopic
      double label immunocytochemistry and high magnification microscopy with oil
      immersion to identify putative juxtapositions between NPY and galanin. Our
      studies show that similarly to rats, numerous NPY-IR nerve terminals surrounded
      galanin-IR neurons in the human hypothalamus. Among the hypothalamic regions, the
      infundibulum (infundibular or arcuate nucleus) contained the largest number of
      galanin-IR neurons heavily surrounded with NPY-IR nerve terminals. These en
      passant-type intimate associations between NPY-IR and galanin-IR neuronal
      elements may be functional synapses and may provide the morphological basis for
      the NPY-mediated galanin release. Consequently, NPY-galanin communication may
      mediate effects of NPY on neuronal systems innervated by galanin, and therefore
      may play a pivotal role in the regulation of reproduction, growth, energy and
      metabolism.

PMID- 20678549
TI  - GABAergic basal forebrain afferents innervate selectively GABAergic targets in
      the main olfactory bulb.
AB  - In this work we have analyzed the targets of the GABAergic afferents to the main
      olfactory bulb originating in the basal forebrain of the rat. We combined
      anterograde tracing of 10 kD biotinylated dextran amine (BDA) injected in the
      region of the horizontal limb of the diagonal band of Broca that projects to the
      main olfactory bulb, with immunocytochemical detection of GABA under electron
      microscopy or vesicular GABA transporter (vGABAt) under confocal fluorescent
      microscopy. GABAergic afferents were identified as double labeled BDA-GABA
      boutons. Their targets were identified by their ultrastructure and GABA content.
      We found that GABAergic afferents from the basal forebrain were distributed all
      over the bulbar lamination, but were more abundant in the glomerular and
      inframitral layers (i.e. internal plexiform layer and granule cell layer). The
      fibers had thick varicosities with abundant mitochondria and large perforated
      synaptic specializations. They contacted exclusively GABAergic cells,
      corresponding to type 1 periglomerular cells in the glomerular layer, and to
      granule cells in inframitral layers. This innervation will synchronize the bulbar
      inhibition and consequently the response of the principal cells to the olfactory
      input. The effect of the activation of this pathway will produce a disinhibition
      of the bulbar principal cells. This facilitation might occur at two separate
      levels: first in the terminal tufts of mitral and tufted cells via inhibition of
      type 1 periglomerular cells; second at the level of the firing of the principal
      cells via inhibition of granule cells. The GABAergic projection from the basal
      forebrain ends selectively on interneurons, specifically on type 1 periglomerular
      cells and granule cells, and is likely to control the activity of the olfactory
      bulb via disinhibition of principal cells. Possible similarities of this pathway
      with the septo-hippocampal loop are discussed.

PMID- 20678550
TI  - Peripheral adenosine A2A receptors are involved in carrageenan-induced mechanical
      hyperalgesia in mice.
AB  - Here we studied the role of peripheral adenosine A(2A) receptors in mechanical
      hyperalgesia during inflammation using mice lacking the A(2A) receptors.
      Unilateral s.c. administration of the local inflammatory agent lambda-carrageenan
      induced profound mechanical hyperalgesia 24 h after administration in the
      ipsilateral hind paw in wild-type mice. In homozygous mice lacking the A(2A)
      receptors, carrageenan-induced hyperalgesia was significantly reduced compared to
      wild type controls. The reduction in inflammatory hyperalgesia seen in A(2A)
      receptor knock-out mice was not associated with changes in paw edema. CGS 21680,
      a selective A(2A) receptor agonist, produced significantly more mechanical
      hyperalgesia in wild type females than in wild type males upon direct s.c.
      injection into the hindpaw whereas it had no effect upon systemic administration.
      The hyperalgesic effect of CGS 21680 was markedly reduced in the A(2A) knock-out
      mice of both sexes. Subcutaneous ZM-241,385, a selective A(2A) receptor
      antagonist, injected into the hindpaw reduced the mechanical hyperalgesia
      following carrageenan in female mice, but not in males. The results indicate that
      activation of peripheral adenosine A(2A) receptors during inflammation is
      associated with mechanical hyperalgesia, and that this effect is more prominent
      in females than in males.

PMID- 20678551
TI  - Acute effects of sublingual buprenorphine on brain responses to heroin-related
      cues in early-abstinent heroin addicts: an uncontrolled trial.
AB  - Replacement therapy with buprenorphine is clinically effective in reducing
      withdrawal and craving for heroin during detoxification but not in decreasing the
      probability of relapse after detoxification. This study examined the acute
      effects of buprenorphine on brain responses to heroin-related cues to reveal the
      neurobiological and therapeutic mechanisms of addiction and relapse. Fifteen
      heroin addicts at a very early period of abstinence, were studied in two separate
      periods 10-15 min apart: an early period (5-45 min) and a later period (60-105
      min) after sublingual buprenorphine, roughly covering the onset and peak of
      buprenorphine plasma level. During both periods, fMRI scanning with heroin
      related visual stimuli were performed followed by questionnaires. Under effect of
      buprenorphine, brain responses to heroin-related cues showed decrease in
      amygdala, hippocampus, ventral tegmental area (VTA) and thalamus but no changes
      in ventral striatum and orbital-prefrontal-parietal cortices. As an uncontrolled
      trial, these preliminary results suggest that buprenorphine has specific brain
      targets in reducing withdrawal and craving during early abstinence, and that
      ventral striatum and orbital-prefrontal-parietal cortices may be the key targets
      in developing therapy for drug addiction and relapse.

PMID- 20678552
TI  - Selective up-regulation of the vasodilator peptide apelin after dorsal root but
      not after spinal nerve injury.
AB  - Regeneration of sensory neurons is limited in response to lesion of their central
      axons when compared to lesion of their peripheral axons. To identify
      transcriptional changes underlying this differential regenerative response
      between dorsal root and spinal nerve axons, the L5 dorsal root ganglion (DRG) of
      adult rats was investigated three days after crushing the respective nerve
      branches by performing high density genome oligonucleotide microarrays. RT-PCR,
      in situ hybridization and immunohistochemistry confirmed the up-regulation of the
      vasodilator peptide apelin in non-neuronal cells of the DRG after dorsal root but
      not after spinal nerve lesion. Induction of apelin mRNA and peptide is
      accompanied by increased vascular permeability around neuronal cell bodies as
      demonstrated by Evans-blue albumin (EBA) leakage. Enhanced vasodilation and
      increased vascular permeability cause intraganglionic edema, which may play a key
      role in the reduced axonal regeneration rate after dorsal root injury.

PMID- 20678553
TI  - Cognition in transmembrane domain neuregulin 1 mutant mice.
AB  - Neuregulin 1 (NRG1), which has been implicated in the development of
      schizophrenia, is expressed widely throughout the brain and influences key
      neurodevelopmental processes such as myelination and neuronal migration. The
      heterozygous transmembrane domain Nrg1 mutant mouse (Nrg1 TM HET) exhibits a
      neurobehavioural phenotype relevant for schizophrenia research, characterized by
      the development of locomotor hyperactivity, social withdrawal, increased
      sensitivity to environmental manipulation, and changes to the serotonergic
      system. As only limited data are available on the learning and memory performance
      of Nrg1 TM HET mice, we conducted a comprehensive examination of these mice and
      their wild type-like littermates in a variety of paradigms, including fear
      conditioning (FC), radial arm maze (RAM), Y maze, object exploration and passive
      avoidance (PA). Male neuregulin 1 hypomorphic mice displayed impairments in the
      novel object recognition and FC tasks, including reduced interest in the novel
      object and reduced FC to a context, but not a discrete cue. These cognitive
      deficits were task-specific, as no differences were seen between mutant and
      control mice in spatial learning (i.e. RAM and Y maze) for both working and
      reference memory measures, or in the PA paradigm. These findings indicate that
      neuregulin 1 plays a moderate role in cognition and present further behavioural
      validation of this genetic mouse model for the schizophrenia candidate gene
      neuregulin 1.

PMID- 20678554
TI  - Cyclooxygenase and nitric oxide synthase in the presympathetic neurons in the
      paraventricular hypothalamic nucleus are involved in restraint stress-induced
      sympathetic activation in rats.
AB  - Stress is one of the important factors to activate the sympathetic nervous
      system. We recently reported that central administration of corticotropin
      releasing factor (CRF), known as a stress-related neuropeptide, increases the
      expression of both cyclooxygenase (COX) and nitric oxide synthase (NOS) in
      presympathetic neurons in the paraventricular hypothalamic nucleus (PVN). In the
      present study, therefore, we investigated whether brain COX and NOS can also
      mediate restraint stress (RS)-induced sympathetic activation by assessing the
      plasma catecholamine levels and neuronal activation of presympathetic neurons in
      the PVN. In addition, we examined effects of RS on the expression of both COX and
      NOS isozymes in the presympathetic PVN neurons. Intraperitoneal administration of
      an inhibitor for COX-1, COX-2 or inducible NOS (iNOS), but not for neuronal NOS
      (nNOS), reduced RS-induced elevation of plasma catecholamine levels and Fos
      expression in the presympathetic PVN neurons. Moreover, RS increased the
      expression of COX-1, COX-2 and iNOS in the presympathetic PVN neurons, whereas
      nNOS expression did not change. These results suggest that COX-1, COX-2 and iNOS
      in the presympathetic PVN neurons mediate acute RS-induced sympathetic
      activation.

PMID- 20678555
TI  - Genetic markers of striatal dopamine predict individual differences in
      dysfunctional, but not functional impulsivity.
AB  - Various psychiatric disorders are characterized by elevated levels of
      impulsivity. Although extensive evidence supports a specific role of striatal,
      but not frontal dopamine (DA) in human impulsivity, recent studies on genetic
      variability have raised some doubts on such a role. Importantly, impulsivity
      consists of two dissociable components that previous studies have failed to
      separate: functional and dysfunctional impulsivity. We compared participants with
      a genetic predisposition to have relatively high striatal DA levels (DAT1 9
      repeat carriers, DRD2 C957T T/T homozygotes, and DRD4 7-repeat carriers) with
      participants with other genetic predispositions. We predicted that the first
      group would show high scores of dysfunctional, but not functional, self-reported
      impulsivity and greater difficulty in inhibiting a behavioral response to a stop
      signal, a behavioral measure of impulsivity. In a sample of 130 healthy adults,
      we studied the relation between DAT1, DRD4, and C957T polymorphism at the DRD2
      gene (polymorphisms related to striatal DA) and catechol-Omethyltransferase
      (COMT) Val158Met (a polymorphism related to frontal DA) on self-reported
      dysfunctional and functional impulsivity, assessed by the Dickman impulsivity
      inventory (DII), and the efficiency of inhibitory control, assessed by the stop
      signal paradigm. DRD2 C957T T/T homozygotes and DRD4 7-repeat carriers indeed had
      significantly higher scores on self-reported dysfunctional, but not functional,
      impulsivity. T/T homozygotes were also less efficient in inhibiting prepotent
      responses. Our findings support the claim that dopaminergic variation affects
      dysfunctional impulsivity. This is in line with the notion that the over-supply
      of striatal DA might weaken inhibitory pathways, thereby enhancing the activation
      of, and the competition between responses.

PMID- 20678557
TI  - Potential insulin secretagogue effects of isovitexin and swertisin isolated from
      Wilbrandia ebracteata roots in non-diabetic rats.
AB  - The antihyperglycemic effect and mechanism of action of extracts, fractions and
      compounds from Wilbrandia ebracteata was studied. The crude extract reduced the
      glycemia, increased glycogen content and serum insulin in hyperglycemic rats.
      Also, a significant effect was observed with the n-butanol and metanol
      subfraction. However, the antihyperglycemic effect of the n-butanol fraction was
      not observed in diabetic rats. The C-glycosylflavones isovitexin and swertisin
      showed a strong antihyperglycemic action compared with the extracts and
      fractions. These results show that the extracts, fractions, and isolated C
      glycosylflavones have an antihyperglycemic action that was reinforced by the
      stimulation on in vivo insulin secretion.

PMID- 20678556
TI  - Minocycline prevents impaired glial glutamate uptake in the spinal sensory
      synapses of neuropathic rats.
AB  - Activation of glutamate receptors and glial cells in the spinal dorsal horn are
      two fundamental processes involved in the pathogenesis of various pain
      conditions, including neuropathic pain induced by injury to the peripheral or
      central nervous systems. Numerous studies have demonstrated that minocycline
      treatment attenuates allodynic and hyperalgesic behaviors induced by tissue
      inflammation or nerve injury. However, the synaptic mechanisms by which
      minocycline prevents hyperalgesia are not fully understood. We recently reported
      that deficient glutamate uptake by glial glutamate transporters (GTs) is key for
      the enhanced activation of N-methyl-d-aspartate (NMDA) receptors in the spinal
      sensory synapses of rats receiving partial sciatic nerve ligation (pSNL). In this
      study, we investigated how minocycline affects activation of NMDA receptors in
      the spinal sensory synapses in rats with pSNL by whole cell recordings of NMDA
      currents in spinal laminea I and II neurons from spinal slices. The effects of
      minocycline treatments on the dorsal horn expression of glial GTs and astrocyte
      marker glial fibrillary acidic protein (GFAP) were analyzed by
      immunohistochemistry. We demonstrated that normalized activation of NMDA
      receptors in synapses activated by both weak and strong peripheral input in the
      spinal dorsal horn is temporally associated with attenuated mechanical allodynia
      in rats with pSNL receiving intraperitoneal injection of minocycline. Minocycline
      ameliorated both the downregulation of glial GT expression and the activation of
      astrocytes induced by pSNL in the spinal dorsal horn. We further revealed that
      preventing deficient glial glutamate uptake at the synapse is crucial for
      preserving the normalized activation of NMDA receptors in the spinal sensory
      synapses in pSNL rats treated with minocycline. Our studies suggest that glial
      GTs may be a potential target for the development of analgesics.

PMID- 20678558
TI  - Antifungal properties of methanol extract and its active compounds from
      Brickellia rosmarinifolia Vent.
AB  - A new isocoumarin, 7-hydroxyl-4-methyl isocoumarine (1), together with three
      known monoterpenes, (3R, 4R, 6S)-3, 6-dihydroxy-1-menthene (2), (+)-(1R, 3S, 4R,
      6S)-6-hydroxymenthol (3) and 4-isopropyl-1-methylcyclohex-2-ene-1, 6-diol (4),
      was isolated from the methanol extract of Brickellia rosmarinifolia. The
      structures were determined by spectroscopic means. Compounds 1, 2, 3 and 4 showed
      antifungal activities against Colletotrichum musae and Peronophythora litchii in
      vitro.

PMID- 20678559
TI  - The role of cyclooxygenase-2-dependent signaling via cyclic AMP response element
      activation on aromatase up-regulation by o,p'-DDT in human breast cancer cells.
AB  - o,p'-Dichlorodiphenyltrichloroethane (o,p'-DDT) is a DDT isomer and xenoestrogen
      that can induce inflammation and cancer. However, the effect of o,p'-DDT on
      aromatase is unclear. Thus, we investigated the effects of o,p'-DDT on aromatase
      expression in human breast cancer cells. We also examined whether cyclooxygenase
      2 (COX-2) is involved in o,p'-DDT-mediated aromatase expression. Treatment with
      o,p'-DDT-induced aromatase protein expression in MCF-7 and MDA-MB-231 human
      breast cancer cells; enhancing aromatase gene expression, and enzyme and promoter
      activity. Treatment with ICI 182.780, a estrogen receptor antagonist, did not
      affect the inductive effects of o,p'-DDT on aromatase expression. In addition,
      o,p'-DDT increased COX-2 protein levels markedly, increased COX-2 mRNA expression
      and promoter activity, enhanced the production of prostaglandin E(2) (PGE(2)),
      induced cyclic AMP response element (CRE) activation, and cAMP levels and binding
      of CREB. o,p'-DDT also increased the phosphorylation of PKA, Akt, ERK, and JNK in
      their signaling pathways in MCF-7 and MDA-MB-231 cells. Finally, o,p'-DDT
      induction of aromatase was inhibited by various inhibitors [COX-2 (by NS-398),
      PKA (H-89), PI3-K/Akt (LY 294002), EP2 (AH6809), and EP4 receptor (AH23848)].
      Together, these results suggest that o,p'-DDT increases aromatase, and that o,p'
      DDT-induced aromatase is correlated with COX-2 up-regulation, mediated via the
      CRE activation and PKA and PI3-kinase/Akt signaling pathways in breast cancer
      cells.

PMID- 20678560
TI  - Sustained release coating of tablets with Eudragit((r)) RS/RL using a novel
      electrostatic dry powder coating process.
AB  - The objectives of this study were to develop an electrostatic dry powder coating
      process for sustained coating tablets with Eudragit((r)) RS/RL and to investigate
      the effects of various factors and operating conditions on the coating process
      and drug release profile. A liquid plasticizer (triethyl citrate) was sprayed
      onto the surface of the tablets followed by spraying coating powder by an
      electrostatic spray gun. The powder coated tablets were cured at elevated
      temperature for a film formation. Liquid plasticizer played important roles in
      lowering down the glass transition temperature (T(g)) of the coating polymer and
      increasing the surface electrical conduction of tablet cores. Electrostatic
      assisted coating deposition was confirmed by the fact that higher coating level
      was obtained with electrical charging than the ones without it. The micrographs
      of scanning electron microscopy (SEM) of coated tablets showed that the film
      formation mainly occurred during the curing step. Higher curing temperature and
      longer curing time help enhance the film formation. The in vitro drug release
      profiles indicated that curing time, temperature, coating level and ratio of
      Eudragit((r)) RS/RL were the main factors affecting the sustained release
      profile. The electrostatic dry powder coating process has been demonstrated to be
      an alternative for tablet sustained release coating with Eudragit((r)) RS and RL.

PMID- 20678561
TI  - Alternative oral exemestane formulation: improved dissolution and permeation.
AB  - Exemestane (EXE) is an irreversible aromatase inactivator used for the treatment
      of advanced postmenopausal breast cancer. EXE is orally active but its
      bioavailability is about 5% due to its low solubility in water and the extensive
      first pass effect. It is known that cyclodextrin (CD) complexation enhances
      solubility and oral bioavailability of poorly soluble drugs. Thus, it was aimed
      to design and develop cyclodextrin complexes in powder and tablet forms
      containing EXE to improve aqueous solubility and in vitro permeability. In this
      study, inclusion complexes of EXE were prepared with three different CD
      derivatives (methyl-beta-cyclodextrin, hydroxypropyl-beta-cyclodextrin and
      hydroxypropyl-gamma-cyclodextrin) and by two different preparation methods
      (kneading and colyophilization) and the complexes were characterized with (1)H
      NMR, FT-IR, SEM, X-ray and DSC analyses. Both inclusion complexes and tablet
      formulations prepared using EXE:CD inclusion complexes showed significant
      improvement in the dissolution profile of this oral antiestrogen drug.
      Furthermore, Caco-2 cell permeation studies revealed that apparent permeability
      constant for EXE was increased by 3-fold via cyclodextrin complexation. In
      conclusion, complexation of EXE with cyclodextrin derivatives, randomly
      methylated-beta-cyclodextrin in particular, results in a more efficient tablet
      formulation with improved dissolution and better permeation suggesting an
      enhancement in oral bioavailability of the drug.

PMID- 20678562
TI  - Application of partial least-squares (PLS) modeling in quantifying drug
      crystallinity in amorphous solid dispersions.
AB  - Among the different experimental methods that can be used to quantify the
      evolution of drug crystallinity in polymer-containing amorphous solid
      dispersions, powder X-ray diffractometry (PXRD) is commonly considered as a
      frontline method. In order to achieve accurate quantification of the percent drug
      crystallinity in the system, calibration curves have to be constructed using
      appropriate calibration samples and calculation methods. This can be non-trivial
      in the case of partially crystalline solid dispersions where the calibration
      samples must capture the multiphase nature of the systems and the mathematical
      model must be robust enough to accommodate subtle and not so subtle changes in
      the diffractograms. The purpose of this study was to compare two different
      calculation and model-building methods to quantify the proportion of crystalline
      drug in amorphous solid dispersions containing different ratios of drug and
      amorphous polymer. The first method involves predicting the % drug crystallinity
      from the ratio of the area underneath the Bragg peaks to total area of the
      diffractogram. The second method is multivariate analysis using a Partial Least
      Squares (PLS) multivariate regression method. It was found that PLS analysis
      provided far better accuracy and prediction of % drug crystallinity in the
      sample. Through the application of PLS, root-mean-squared error of estimation
      (RMSEE) values of 2.2%, 1.9%, and 4.7% drug crystallinity was achieved for
      samples containing 25%, 50%, and 75% polymer, respectively, compared to values of
      11.2%, 17.0%, and 23.6% for the area model. In addition, construction of a PLS
      model enables further analysis of the data, including identification of outliers
      and non-linearity in the data, as well as insight into which factors are most
      important to correlate PXRD diffractograms with % crystallinity of the drug
      through analysis of the loadings.

PMID- 20678563
TI  - Nigericin-mediated liposome loading of topotecan: is nigericin a potential drug
      release regulator?
AB  - Topotecan was loaded into large unilamellar vesicles using nigericin-generated pH
      gradient or with triethylammonium (TA) ion gradient. Despite that in both loading
      methods, the encapsulated counter ion was 5-sulfosalicylate (5ssa), the resultant
      formulations exhibited distinct properties. In NaCl-containing release buffer,
      vesicles prepared with nigericin/Na(+) system could release topotecan at a faster
      rate than 5ssa-TA vesicles, whereas in the absence of Na(+), there was no
      difference in the drug release kinetics. In plasma, both formulations could
      prolong the circulation halftime of topotecan, but 5ssa-TA vesicles were more
      able to stabilize the encapsulated topotecan, as evidenced by the increased
      t(1/2) and decreased conversion of lactone to carboxylate form. However, the
      improved drug retention did not mean the elevated safety and efficacy. In L1210
      ascitic tumor model, the administration of 5ssa-TA vesicles at 10mg/kg induced
      the early death of ~60% mice at 6-7 days. In contrast, the treatment with
      nigericin/Na(+) vesicles at the same dose level resulted in a mean survival time
      of ~18.0 days, ~1.38-fold of that of free topotecan. In addition, the formulation
      was safer than free topotecan. The results indicated that nigericin could be used
      as release regulator to optimize drug release kinetics, resulting in safe and
      efficacious liposome-based topotecan formulation. The results were promising
      since no liposome topotecan formulations with reduced toxicity were reported.

PMID- 20678564
TI  - Poly(alpha-glutamic acid) combined with polycation as serum-resistant carriers
      for gene delivery.
AB  - The transfection efficiency of cationic polymers decreases dramatically in the
      presence of serum, which hampers the in vivo application of these polymers for
      gene delivery. Due to its shielding effect of poly(alpha-glutamic acid) (PGA)
      from negatively charged serum proteins, it was introduced into DNA polyplexes to
      overcome the serum inhibitory effect. In the present studies, the transfection
      efficiency of DNA/PEI/PGA terplex system was compared to PEI 25 kDa and
      Lipofectamine 2000 in the presence of serum. The successful formation of
      DNA/PEI/PGA terplexes was confirmed by their near-neutral surface charge.
      Interaction between components in the terplex system demonstrated that PGA was
      competing with DNA to combine with PEI. PEI/PGA combined carriers were not
      cytotoxic at a C/N ratio higher than 0.3. The in vitro transfection efficiency of
      DNA/PEI/PGA terplexes was not significantly different from those of DNA/PEI25kDa
      in serum-free medium. Importantly, in serum-containing medium, the DNA terplexes
      at their optimal C/N ratios maintained the same level of transfection efficiency
      as that of serum-free medium, even though the transfection efficiency of PEI 25
      kDa and Lipofectamine 2000 was significantly decreased under serum-containing
      conditions. CLSM results confirmed that the cellular import of pDNA delivered by
      PEI/PGA combined carriers was more efficient than PEI 25 kDa alone under serum
      containing conditions. Therefore, PGA could be used as a versatile serum
      resistant reagent to overcome the serum inhibitory effect of polycations for gene
      delivery.

PMID- 20678565
TI  - Chronological changes in compromised olivocochlear activity and the effect of
      insulin in diabetic Wistar rats.
AB  - The aims of the present study were to investigate in diabetic rats: (1) the
      chronological changes of compromised medial olivocochlear bundle (MOCB) activity
      and auditory brainstem responses (ABR) and (2) the effect of insulin on diabetes
      related hearing dysfunction. Diabetes mellitus was induced by intraperitoneal
      injection of streptozotocin. Thirty male Wistar rats were divided into three
      groups: control (C), diabetes with insulin injection (DI), and diabetes without
      insulin injection (DM). Click-evoked ABR, distortion product otoacoustic emission
      (DPOAE) and the contralateral suppression (CS) of DPOAE were measured for all
      animals monthly. Throughout the experiment, the thresholds of click-evoked ABR
      did not differ among groups. Wave III was delayed and interpeak latency I-III was
      prolonged in the DM group at the age of 29 weeks (p < 0.05). The amplitudes of
      the CS of DPOAE were markedly decreased after the 25th week in the DM group, but
      not in the C and DI groups. Compared to the C group, the CS in the DI group was
      not attenuated at any frequency. Dysfunction of auditory efferent olivocochlear
      activity developed in diabetic rats presenting no evidence of hearing loss. The
      finding of a significant decrease of the CS of DPOAE could be used as an earlier
      indicator of diabetes-related hearing impairment than changes of ABRs. The time
      course of compromised MOCB is positively correlated with the duration of
      diabetes. Insulin could therefore protect against compromised MOCB.

PMID- 20678566
TI  - Is lack of "education" a mechanism driving loss of tolerance in Crohn's disease?

PMID- 20678567
TI  - Natural pharmacopoeia used in traditional Toba medicine for the treatment of
      parasitosis and skin disorders (Central Chaco, Argentina).
AB  - AIM OF THE STUDY: To assess the knowledge and use of natural pharmacopoeia for
      the treatment of parasitosis and skin disorders, as well as for the control of
      their etiological agents or vectors, of a Toba community in Central Chaco,
      Argentina. MATERIALS AND METHODS: Information was obtained by open, extensive and
      recurrent interviews and semi-structured surveys. Plant and animal pharmacopoeia
      was documented by collecting material in field assays carried out in the company
      of informers. The list of applications with the greatest consensus of uses, the
      list of species with most medicinal applications and the list of species with the
      highest reputation (according to the level of fidelity) for the aforementioned
      disorders were obtained using quantitative methods. RESULTS: A total of 178
      medicinal uses were documented corresponding to 87 species (72 plant and 15
      animal species) belonging to 51 different families (39 plant and 12 animal
      families). The most represented families according to the number of species were
      Solanaceae (7 species), Asteraceae (6 species) and Fabaceae (5 species) for
      plants, and Bovidae (3 species) for animals. CONCLUSIONS: Although the list of
      medicinal species includes some symbolical applications, others are supported by
      phytochemical information. In other cases the applications coincide with other
      pharmacopoeias of the Gran Chaco region indicating the presence of an active
      exchange of knowledge through interethnic contacts.

PMID- 20678568
TI  - Minimum inhibitory concentrations of medicinal plants used in Northern Peru as
      antibacterial remedies.
AB  - AIM: The plant species reported here are traditionally used in Northern Peru to
      treat bacterial infections, often addressed by the local healers as
      "inflammation". The aim of this study was to evaluate the minimum inhibitory
      concentration (MIC) of their antibacterial properties against gram-positive and
      gram-negative bacteria. MATERIALS AND METHODS: The antimicrobial activity of
      ethanolic and water extracts of 141 plant species was determined using a deep
      well broth microdilution method on commercially available bacterial strains.
      RESULTS: The ethanolic extracts of 51 species inhibited Escherichia coli, and 114
      ethanolic extracts inhibited Staphylococcus aureus. In contrast, only 30 aqueous
      extracts showed activity against Escherichia coli and 38 extracts against
      Staphylococcus aureus. The MIC concentrations were mostly very high and ranged
      from 0.008 to 256 mg/ml, with only 36 species showing inhibitory concentrations
      of <4 mg/ml. The ethanolic extracts exhibited stronger activity and a much
      broader spectrum of action than the aqueous extracts. Hypericum laricifolium,
      Hura crepitans, Caesalpinia paipai, Cassia fistula, Hyptis sidifolia, Salvia sp.,
      Banisteriopsis caapi, Miconia salicifolia and Polygonum hydropiperoides showed
      the lowest MIC values and would be interesting candidates for future research.
      CONCLUSIONS: The presence of antibacterial activity could be confirmed in most
      species used in traditional medicine in Peru which were assayed in this study.
      However, the MIC for the species employed showed a very large range, and were
      mostly very high. Nevertheless, traditional knowledge might provide some leads to
      elucidate potential candidates for future development of new antibiotic agents.

PMID- 20678569
TI  - Piper umbellatum L.: a comparative cross-cultural analysis of its medicinal uses
      and an ethnopharmacological evaluation.
AB  - AIM OF THE STUDY: This review assesses the botany, traditional medicinal uses,
      phytochemistry, pharmacology and toxicology of P. umbellatum. MATERIALS AND
      METHODS: Information on P. umbellatum was gathered via the internet (using
      Scirus, Google Scholar, CAB-Abstracts, MedlinePlus, Embase, Scielo, and Web of
      Science) and libraries. Additionally, previously unpublished work on the
      traditional uses of P. umbellatum from our National Study of the Medicinal Plants
      of the Dominican Republic has been included. RESULTS: Piper umbellatum is a
      Neotropical plant species widely distributed in Mexico, Central America, South
      America and the West Indian Islands. It has also been introduced to Africa and
      South-East Asia. Traditional uses for this plant are recorded in 24 countries in
      three continents, America, Africa and Asia for a wide range of ailments such as
      kidney, women diseases, diarrhea, skin affections, burns, rheumatism, malaria,
      intestinal parasites, inflammation and fever. We have analyzed the cross-cultural
      agreement among traditional uses in different countries and found a high degree
      of consensus for the indications kidney/diuretic, stomachache and wounds.
      Phytochemical studies of P. umbellatum have demonstrated the presence of terpenes
      (mainly found in the essential oil), alkaloids, flavonoids, sterols and other
      classes of secondary metabolites. The extracts and pure compounds derived from P.
      umbellatum show a wide spectrum of pharmacological activities including
      antibacterial, anti-inflammatory, analgesic, antioxidant, cytotoxic,
      antimalarial, antileishmanial, and antitrypanosomal activity. A first commercial
      product is in development, based on the plant's protective characteristics
      against UV irradiation. CONCLUSIONS: The interesting biological activities of P.
      umbellatum need further research in in vivo experiments and clinical studies. The
      outcome of these investigations will determine the possible development of drugs
      from P. umbellatum.

PMID- 20678570
TI  - Selective vulnerability of neurons to acute toxicity after proteasome inhibitor
      treatment: implications for oxidative stress and insolubility of newly
      synthesized proteins.
AB  - Maintaining protein homeostasis is vital to cell viability, with numerous studies
      demonstrating a role for proteasome inhibition occurring during the aging of a
      variety of tissues and, presumably, contributing to the disruption of cellular
      homeostasis during aging. In this study we sought to elucidate the differences
      between neurons and astrocytes in regard to basal levels of protein synthesis,
      proteasome-mediated protein degradation, and sensitivity to cytotoxicity after
      proteasome inhibitor treatment. In these studies we demonstrate that neurons have
      an increased vulnerability, compared to astrocyte cultures, to proteasome
      inhibitor-induced cytotoxicity. No significant difference was observed between
      these two cell types in regard to the basal rates of protein synthesis, or basal
      rates of protein degradation, in the pool of short-lived proteins. After
      proteasome inhibitor treatment neuronal crude lysates were observed to undergo
      greater increases in the levels of ubiquitinated and oxidized proteins and
      selectively exhibited increased levels of newly synthesized proteins accumulating
      within the insoluble protein pool, compared to astrocytes. Together, these data
      suggest a role for increased oxidized proteins and sequestration of newly
      synthesized proteins in the insoluble protein pool, as potential mediators of the
      selective neurotoxicity after proteasome inhibitor treatment. The implications
      for neurons exhibiting increased sensitivity to acute proteasome inhibitor
      exposure, and the corresponding changes in protein homeostasis observed after
      proteasome inhibition, are discussed in the context of both aging and age-related
      disorders of the nervous system.

PMID- 20678572
TI  - Fibroblast growth factor-2 binding to the endothelial basement membrane peaks at
      a physiologically relevant shear stress.
AB  - Fibroblast growth factor-2 (FGF2) is produced and released by endothelial cells
      and binds to heparan sulfate proteoglycans in the endothelial basement membrane
      (BM), an important FGF2 storage reservoir. Experimental and computational models
      of FGF2 binding kinetics to both cells and BM under static conditions are well
      established in the literature but remain largely unexplored under flow. We now
      examine BM-FGF2 binding kinetics in fluid flow conditions. We hypothesized that
      FGF2 binding to the endothelial BM would decrease as fluid shear stress
      increased. To investigate this, BM-FGF2 equilibrium, associative, and
      dissociative bindings were measured at various shear stresses. Surprisingly, FGF2
      binding increased up to a physiological arterial shear stress of 25 dynes/cm2,
      after which it decreased to a level similar to the 1 dyne/cm2 condition. Both BM
      FGF2 dissociation and BM binding site availability increased with flow, while
      association remained constant. This suggests that force-dependent FGF2
      equilibrium binding varies with shear stress due to a combination of an increase
      in binding site availability and FGF2 dissociation with flow. This improved
      understanding of BM-FGF2 binding with flow enriches current knowledge of FGF2
      binding kinetics under physiologic conditions, which may contribute to improved
      growth factor therapy development.

PMID- 20678571
TI  - Cardiac overexpression of insulin-like growth factor 1 attenuates chronic alcohol
      intake-induced myocardial contractile dysfunction but not hypertrophy: Roles of
      Akt, mTOR, GSK3beta, and PTEN.
AB  - Chronic alcohol intake leads to the development of alcoholic cardiomyopathy
      manifested by cardiac hypertrophy and contractile dysfunction. This study was
      designed to examine the effects of transgenic overexpression of insulin-like
      growth factor 1 (IGF-1) on alcohol-induced cardiac contractile dysfunction. Wild
      type FVB and cardiac-specific IGF-1 mice were placed on a 4% alcohol or control
      diet for 16weeks. Cardiac geometry and mechanical function were evaluated by
      echocardiography and cardiomyocyte and intracellular Ca(2+) properties.
      Histological analyses for cardiac fibrosis and apoptosis were evaluated by Masson
      trichrome staining and TUNEL assay, respectively. Expression and phosphorylation
      of Cu/Zn superoxide dismutase (SOD1), Ca(2+) handling proteins, and key signaling
      molecules for survival including Akt, mTOR, GSK3beta, Foxo3a, and the negative
      regulator of Akt, phosphatase and tensin homolog on chromosome 10 (PTEN), as well
      as mitochondrial proteins UCP-2 and PGC1alpha, were evaluated by Western blot
      analysis. Chronic alcohol intake led to cardiac hypertrophy, interstitial
      fibrosis, reduced mitochondrial number, compromised cardiac contractile function
      and intracellular Ca(2+) handling, decreased SOD1 expression, elevated superoxide
      production, and overt apoptosis, all of which, with the exception of cardiac
      hypertrophy, were abrogated by the IGF-1 transgene. Immunoblotting data showed
      reduced phosphorylation of Akt, mTOR, GSK3beta, and Foxo3a; upregulated Foxo3a
      and PTEN; and dampened SERCA2a, PGC1alpha, and UCP-2 after alcohol intake. All
      these alcohol-induced changes in survival and mitochondrial proteins were
      alleviated by IGF-1. Taken together, these data favor a beneficial role for IGF-1
      in alcohol-induced myocardial contractile dysfunction independent of cardiac
      hypertrophy.

PMID- 20678573
TI  - Mineralocorticoid and glucocorticoid receptors in sciatic nerve function and
      regeneration.
AB  - The contribution of the two corticosteroid (mineralocorticoid and glucocorticoid)
      receptor (MR and GR) pathways to the function and regeneration of the sciatic
      nerve was investigated. We found that the corticosterone-inactivating enzyme
      11beta-hydroxysteroid dehydrogenase type 2 (HSD2) was up-regulated 7 days after
      lesion in freeze-injured nerve. The maintenance of a low intracellular level of
      corticosterone by HSD2 activity in the regenerating nerve is concordant with the
      improvement of nervous function in injured animals (as measured by walking
      ability) after treatment by the GR antagonist mifepristone and with the reduction
      in GR participation in accumulation of the mRNA for numerous endogenous genes
      (from the renin-angiotensin system and other classical mineralocorticoid
      responsive genes), in the same animals. Furthermore, using the MR antagonist
      spironolactone, we demonstrated that MR plays an active role in the function of
      the intact sciatic nerve: MR is required for walking ability and participates in
      the control of the accumulation of the mRNA for several endogenous genes.
      However, after injury, changes in gene expression cannot be fully explained by
      changes in MR/GR activity, due to an HSD2 effect, and other signalling pathway(s)
      induced by the lesion likely combine with the effect of the corticosteroid
      receptors.

PMID- 20678574
TI  - Ephrin-B3 regulates glutamate receptor signaling at hippocampal synapses.
AB  - B-ephrin-EphB receptor signaling modulates NMDA receptors by inducing tyrosine
      phosphorylation of NR2 subunits. Ephrins and EphB RTKs are localized to
      postsynaptic compartments in the CA1, and therefore potentially interact in a non
      canonical cis- configuration. However, it is not known whether cis- configured
      receptor-ligand signaling is utilized by this class of RTKs, and whether this
      might influence excitatory synapses. We found that ablation of ephrin-B3 results
      in an enhancement of the NMDA receptor component of synaptic transmission
      relative to the AMPA receptor component in CA1 synapses. Synaptic AMPA receptor
      expression is reduced in ephrin-B3 knockout mice, and there is a marked
      enhancement of tyrosine phosphorylation of the NR2B receptor subunit. In a
      reduced system co-expression of ephrin-B3 attenuated EphB2-mediated NR2B tyrosine
      phosphorylation. Moreover, phosphorylation of EphB2 was elevated in the
      hippocampus of ephrin-B3 knockout mice, suggesting that regulation of EphB2
      activity is lost in these mice. Direct activation of EphB RTKs resulted in
      phosphorylation of NR2B and a potential signaling partner, the non-receptor
      tyrosine kinase Pyk2. Our data suggests that ephrin-B3 limits EphB RTK-mediated
      phosphorylation of the NR2B subunit through an inhibitory cis- interaction which
      is required for the correct function of glutamatergic CA1 synapses.

PMID- 20678576
TI  - High-level expression and reconstitution of active Cfr, a radical-SAM rRNA
      methyltransferase that confers resistance to ribosome-acting antibiotics.
AB  - Cfr is a radical-SAM (S-adenosyl-L-methionine) enzyme that methylates the 8
      position of 23S rRNA residue A2503 to confer resistance to multiple antibiotic
      classes acting upon the large subunit of the bacterial ribosome. Radical-SAM
      enzymes use an Fe-S cluster to generate the 5'-deoxyadenosyl (DOA) radical from
      SAM, enabling them to modify intrinsically unreactive centres such as adenosine
      C8. However, despite its mechanistic interest and clinical relevance, until
      recently Cfr remained little characterised. Accordingly we have used co
      expression with the Azotobacter vinelandii isc operon, encoding genes responsible
      for Fe-S cluster biosynthesis, to express hexahistidine-tagged Cfr in Escherichia
      coli BL21Star, and purified the recombinant protein in a yield more than 20 times
      greater than has been previously reported. As aerobically purified, Cfr contains
      secondary structure, is monomeric in solution and has an absorbance spectrum
      suggestive of a 2Fe-2S cluster. After anaerobic purification a 4Fe-4S cluster is
      indicated, while on reconstitution with excess iron and sulphide a further
      increase in metal content suggests that an additional, most likely 4Fe-4S,
      cluster is formed. Acquisition of additional secondary structure under these
      conditions indicates that Fe-S clusters are of structural, as well as functional,
      importance to Cfr. In the presence of sodium dithionite reconstituted Cfr is both
      reducible and able to cleave SAM to 5'-deoxyadeonsine (DOA), demonstrating that
      the purified reconstituted enzyme has radical-SAM activity. Co-expression with
      isc proteins thus enables recombinant active Cfr to be obtained in yields that
      facilitate its future spectroscopic and structural characterisation.

PMID- 20678575
TI  - Comparative analysis of Drosophila and mammalian complexins as fusion clamps and
      facilitators of neurotransmitter release.
AB  - The SNARE-binding protein complexin (Cpx) has been demonstrated to regulate
      synaptic vesicle fusion. Previous studies are consistent with Cpx functioning
      either as a synaptic vesicle fusion clamp to prevent premature exocytosis, or as
      a facilitator to directly stimulate release. Here we examined conserved roles of
      invertebrate and mammalian Cpx isoforms in the regulation of neurotransmitter
      release using the Drosophila neuromuscular junction as a model synapse. We find
      that SNARE binding by Cpx is required for its role as a fusion clamp. All four
      mammalian Cpx proteins (mCpx), which have been demonstrated to facilitate
      release, also function as fusion clamps when expressed in Drosophila cpx null
      mutants, though their clamping abilities vary between isoforms. Moreover,
      expression of mCpx I, II or III isoforms dramatically enhance evoked release
      compared to mCpx IV or Drosophila Cpx. Differences in the clamping and
      facilitating properties of complexin isoforms can be partially attributed to
      differences in the C-terminal membrane tethering domain. Our findings indicate
      that the function of complexins as fusion clamps and facilitators of fusion are
      conserved across evolution, and that these roles are genetically separable within
      an isoform and across different isoforms.

PMID- 20678577
TI  - Two pools of vesicles associated with the presynaptic cytosolic projection in
      Drosophila neuromuscular junctions.
AB  - Synapses that sustain neurotransmitter release at high rates often contain
      special presynaptic cytosolic projections (PCPs) that are believed to facilitate
      synaptic vesicle (SV) movements to the sites of fusion. The genetically
      modifiable Drosophila neuromuscular junction (NMJ) serves as one of the model
      systems to investigate the functions of these structures. Using electron
      microscope tomography we determined the three-dimensional organization of the
      Drosophila PCP immobilized by high-pressure freezing, followed by cryo
      substitution. We show that it is composed of three structural components: (1) the
      central core, (2) legs, organized in a regular grid at the bottom of the central
      core, and (3) cytoplasmic extensions. The extensions are comprised of thin
      filaments emerging from the central core. SVs connected to the extensions are
      either linked to the vesicles accumulated around the PCP or to the presynaptic
      membrane. This suggests that SVs associated with the PCP loose their connections
      with other vesicles in the cluster during translocation to the site of fusion.

PMID- 20678579
TI  - Evolution of Sousa chinensis: a scenario based on mitochondrial DNA study.
AB  - Taxonomy within genus Sousa is confused largely due to inconsistencies among
      external morphology, skull morphology, pigmentation patterns and molecular
      studies. Here we provide our understanding of the evolution of Sousa chinensis by
      proposing a phylogeographic history based on mtDNA study. It is proposed that the
      species originated in eastern Australian waters and the current distribution has
      taken shape over the last 8.02-1.24 million years. Populations in Southeast Asia
      and Australian region experienced recent expansion about 0.54-1.5 million years
      ago. It is also proposed that populations in Southeast Asia experienced
      separation, re-unification and further dispersal during the last glacial age with
      multiple north-south migration across the Sahul Shelf area of northern Australia.

PMID- 20678578
TI  - Tractography segmentation using a hierarchical Dirichlet processes mixture model.
AB  - In this paper, we propose a new nonparametric Bayesian framework to cluster white
      matter fiber tracts into bundles using a hierarchical Dirichlet processes mixture
      (HDPM) model. The number of clusters is automatically learned driven by data with
      a Dirichlet process (DP) prior instead of being manually specified. After the
      models of bundles have been learned from training data without supervision, they
      can be used as priors to cluster/classify fibers of new subjects for comparison
      across subjects. When clustering fibers of new subjects, new clusters can be
      created for structures not observed in the training data. Our approach does not
      require computing pairwise distances between fibers and can cluster a huge set of
      fibers across multiple subjects. We present results on several data sets, the
      largest of which has more than 120,000 fibers.

PMID- 20678580
TI  - Ceramide kinase is not essential but might act as an Ca2+-sensor for mast cell
      activation.
AB  - Ceramide kinase (CerK) catalyzes the conversion of ceramide to ceramide 1
      phosphate (C1P). We previously revealed that CerK is involved in the activation
      of mast cells. In this study, we performed an advanced investigation into the
      role of CerK on the activation of mast cells using CERK-/- mice. Although CERK-/-
      mice were less prone to exhibiting a passive cutaneous anaphylactic shock (PCA)
      reaction compared to wild type (WT) mice, the differences were not significant.
      In bone marrow-derived mast cells (BMMC) activated by cross-linking antigen
      (Ag)/IgE, not high, but low concentrations of Ag had a reduced effect on
      degranulation in BMMC from CERK-/- mice compared to effects on BMMC from WT mice.
      Similarly, when the BMMCs were activated with calcium ionophore to focus on the
      downstream signaling of Ca(2+)-elevation, only a low concentration of ionophore
      had a reduced effect on degranulation in the BMMC from CERK-/- mice compared to
      the effect on BMMC from WT mice. Furthermore, the CerK inhibitor K1 reduced the
      differences in degranulation observed between the BMMC from CERK-/- and WT mice
      in a dose-dependent manner, demonstrating a contribution for CerK and its product
      C1P in degranulation. Although CerK is not essential for activation of mast
      cells, especially a potent and acute activation such as a PCA reaction, CerK
      might act as an modulator for mild and chronic activation of mast cells, thus
      increasing sensitivity to cytoplasmic Ca(2+).

PMID- 20678581
TI  - Tau protein: relevance to Parkinson's disease.
AB  - Tau is a microtubule-associated protein linked with neurodegenerative diseases.
      Humans express six different isoforms of tau; the longest containing four
      microtubule-binding repeat motifs in the C-terminal that are vital for what is
      considered the major biological function of tau, to stabilize microtubules and
      facilitate axonal transport. The capacity of tau to maintain its normal
      biological function is dependent upon its phosphorylation state. In Alzheimer's
      and Parkinson's diseases, there is a hyperphosphorylation of tau that leads to
      the intracellular accumulation of tau in the form of neurofibrillary tangles.
      While the role of tau in Parkinson's disease has been understated for some time,
      here we summarize key genetic, pathological and biochemical evidence supporting a
      role for tau in the pathogenesis of Parkinson's disease. Toxic interactions with
      alpha synuclein may lead to hyperphosphorylation of tau and eventually to the
      deposition of both proteins in the disease.

PMID- 20678583
TI  - Medicines discovery in the 21st century: the case for a stakeholder corporation.
AB  - It is widely accepted that biopharmaceutical companies have, in recent times,
      failed to deliver large numbers of new medicines to patients and have
      simultaneously failed to deliver large financial returns to their investors. We
      argue that addition of different business constructs with wider stakeholder
      ownership and/or control offers a way to improve returns from the great advances
      in medical science and drug discovery processes. Governments and other payers for
      medicines, the academic institutions engaged in bioscience knowledge creation,
      patient advocacy groups, venture philanthropists and charitable foundations can
      come together with commercial profit-centred businesses to develop corporate
      constructs that mutually benefit all of the stakeholders. A rebalancing of the
      social and financial motives in medicines research can arrest recent productivity
      decreases of the sector.

PMID- 20678582
TI  - Signalling through FOXP3 as an X-linked tumor suppressor.
AB  - The FOXP3 (forkhead box P3) gene is a member of forkhead winged helix family
      transcription factors and functions as both a transcriptional activator and a
      repressor. FOXP3 dysfunction is responsible for an X-linked autoimmune syndrome:
      immune dysregulation, polyendopathy, enterophathy, X-linked syndrome. In addition
      to its role as an essential transcription factor in regulatory T cells, the FOXP3
      gene is an epithelial cell-intrinsic tumor suppressor for breast and prostate
      cancers. We will focus on the FOXP3 signalling pathway in epithelial cells and
      discuss how genetic and/or epigenetic inactivation of the FOXP3 contributes to
      the malignant transformation of cells.

PMID- 20678584
TI  - Comparative morphology of the hemolymph vascular system in krill (Euphausiacea;
      Crustacea).
AB  - The phylogenetic position of Euphausiacea within Malacostraca is still under
      debate. Either they are seen as sister group to a taxon comprising Pancarida and
      Peracarida or closer related to Decapoda. Both hypotheses can be supported by
      characters of the circulatory system. Therefore, a comparative re-evaluation of
      the circulatory system seems to be feasible. Here we present the first three
      dimensional data of the circulatory system of three euphausiacean species based
      on semi-thin sections and micro computer tomography in combination with corrosion
      casting. We were also able to study for the first time representatives of
      Bentheuphausia amblyops, the suggested sister taxon to all other euphausiaceans.
      The main pumping structure in the open circulatory system of Euphausiacea is the
      globular heart in the rear thoracic segments. From the anterior and posterior end
      of the heart two unpaired and four pairs of arteries emanate. The unpaired
      anterior aorta runs below the carapace from the anterior part of the heart into
      the anterior cephalothorax, where it supplies the first antennae, the brain and
      the eyes. The paired posterior aortae run into the pleon supplying the pleopods,
      uropods and the telson. The four pairs of cardiac arteries supply appendages in
      the cephalic region and viscera in the trunk. The unpaired descending artery
      connects to the subneural vessel supplying the thoracopods. A myoarterial
      formation of the anterior aorta is described in Bentheuphausia amblyops. The
      observed pattern of a globular heart situated in the posterior cephalothorax and
      comprising a meshwork of muscular strands (also running through its lumen) is
      highly likely to be homologous in Euphausiacea and Decapoda. The data are
      compared with the scarce literature present to date.

PMID- 20678585
TI  - Two-stage designs optimal under the alternative hypothesis for phase II cancer
      clinical trials.
AB  - The Simon two-stage optimal design is often used for phase II cancer clinical
      trials. A study proceeds to the second stage unless the null hypothesis, that the
      true tumour response rate is below some specified value, is already accepted at
      the end of stage one. The conventional optimal design, for given type 1 and type
      2 error rates, is the one which minimises the expected sample size under the null
      hypothesis. However, at least some new agents are active, and designs that
      explicitly address this possibility should be considered. We therefore
      investigate novel designs which are optimal under the alternative hypothesis,
      that the tumour response rate is higher than the null hypothesis value, and also
      designs which allow early stopping for efficacy. We make available, software for
      identifying the corresponding optimal and minimax designs. Considerable savings
      in expected sample sizes can be achieved if the alternative hypothesis is in fact
      true, without sample sizes suffering too much if the null hypothesis is true. We
      present an example discussing the merits of different designs in a practical
      context. We conclude that it is relevant to consider optimal designs under a
      range of hypotheses about the true response rate, and that allowing early
      stopping for efficacy is always advantageous in terms of expected sample size.

PMID- 20678586
TI  - Immunogenicity and efficacy of two types of West Nile virus-like particles
      different in size and maturation as a second-generation vaccine candidate.
AB  - Virus-like particles (VLPs) of flaviviruses generated from the prM and E genes
      are a promising vaccine candidate. We have established cell clones continuously
      releasing VLPs of West Nile virus (WNV) in serum-free conditions. Two types of
      VLPs were distinguished by sedimenting analyses in sucrose density gradients.
      Fast sedimenting VLPs (F-VLPs) were large (40-50 nm) and composed of the E and
      processed mature M proteins, whereas slowly sedimenting VLPs (S-VLPs) were small
      (20-30 nm) particles consisting of the E and immature prM proteins. F-VLPs
      induced higher neutralizing antibody and anti-WNV IgG titers than S-VLPs.
      Furthermore, IgG2a was dominant over IgG1 by immunization with F-VLPs as with
      whole virion-derived antigens. Mice vaccinated with a low dose (3 ng) of F-VLPs
      showed higher protective efficacy (83% survivals) against WNV infection than S
      VLP-immune mice (17% survivals). These results indicate that F-VLPs more closely
      resemble the virions and take a better immunogenic form than S-VLPs as WNV
      vaccine candidates.

PMID- 20678587
TI  - The kinetics of soluble and particulate antigen trafficking in the afferent
      lymph, and its modulation by aluminum-based adjuvant.
AB  - Aluminium adjuvants are potent enhancers of immune responses. Despite being a
      component in most human and animal vaccines, their specific mode of action
      remains elusive. We have used a sheep lymphatic cannulation model to directly
      measure the trafficking of soluble and particulate antigen in real-time from the
      site of injection. Aluminium adjuvant does not alter the kinetics of antigen flow
      from the site of injection; however it does reduce the amount of soluble antigen
      entering into afferent lymph. Large numbers of neutrophils, but not DCs, were
      recruited into the lymph in both saline and aluminium-injected sites and were
      predominantly responsible for the early uptake of particulate antigen into the
      lymphatic. Aluminium adjuvant did not significantly increase neutrophil uptake
      but markedly increased the subsequent uptake of particulate antigen by DCs from
      48 to 72 h after antigen injection. Thus, the adjuvanticity of aluminium does not
      correlate with slow antigen release or increased cell recruitment, but with
      retention of antigen at the site of injection, and increased uptake of
      particulate antigen by mature migratory DCs after 24h.

PMID- 20678588
TI  - Immunisation and multi-dose vials.
AB  - The current novel H1N1 09 influenza virus pandemic has resulted in 37,722
      diagnoses, 4992 hospitalisations, and 191 deaths in Australia as of 11 June 2010.
      A mass immunisation campaign has commenced using a multi-dose vial formulation to
      assist rapid deployment. However, in the past multi-dose vials have been
      associated with transmission of infective agents. Having the vaccine in single
      dose vials with a lesser risk of transmission of infection but increased delay in
      implementation and increased cost needs to be weighed against the imperative to
      vaccinate the population against pandemic H1N1 09 influenza virus. This article
      reviews the infectious risks associated with multi-dose vials.

PMID- 20678589
TI  - Constitutive expression of HIV-VLPs in stably transfected insect cell line for
      efficient delivery system.
AB  - We have previously developed HIV-1 Pr55gag-based virus-like particles (HIV-VLPs)
      as presentation and delivery model using a transient Baculovirus expression
      system. Here we describe the establishment and characterization of stably
      transfected insect cell line for the constitutive and reproducible production of
      HIV-VLPs. The persistence of HIV gag coding gene has been verified in clonal
      resistant insect cells and the protein expression has been confirmed by Western
      blot analysis. The resulting HIV-VLPs have been evaluated by standard
      transmission electron microscopy and their immunogenicity has been evaluated in
      vivo. Our results demonstrate that this strategy is highly efficient for
      constitutive expression of conformational enveloped VLPs which can be employed as
      presentation and delivery system for pathogen as well as tumor-associated
      antigens. This represents, to our knowledge, the first example of stably
      transfected insect cell line for the constitutive production of VLPs.

PMID- 20678590
TI  - Genetic characterization of circulating seasonal Influenza A viruses (2005-2009)
      revealed introduction of oseltamivir resistant H1N1 strains during 2009 in
      eastern India.
AB  - Influenza surveillance was implemented in Kolkata, eastern India in 2005 to
      identify the circulating subtypes and characterize their genetic diversity.
      Throat and nasal swabs were collected from outpatients with influenza-like
      illness (ILI). Of 2844 ILI cases identified at two referral hospitals during
      October 2005-September 2009, 309 (10.86%) were positive for Influenza A by real
      time RT-PCR, of which 110 (35.60%) were subtyped as H1N1 and 199 (64.40%) as
      H3N2. Comparison of the nucleotide (nt) and amino acid (aa) sequences of the HA1
      gene for H1N1 and H3N2 strains showed that a subset of strains precede WHO
      recommended contemporary strains by 1-2 years. The Kolkata H1N1 strains clustered
      in Clade II, subgroup 2B with A/Brisbane/59/2007 but were distant from the
      corresponding vaccine strains (New Caledonia/20/99 and A/Solomon Island/3/06).
      The 2005-06 and 2007 H3N2 strains (15/17) clustered either A/Brisbane/10/2007
      like (n=8) or A/Nepal/921/2006 like (n=7) strains, whereas 2008 strains (8/12)
      and 2009 strains (4/4) were similar to the 2010-11 vaccine strain
      A/Perth/16/2009. More aa substitutions were found in HA or NA genes of H3N2 than
      in H1N1 strains. No mutation conferring neuraminidase resistance was observed in
      any of the strain during 2005-08, however in 2009, drug resistant marker (H275Y)
      was present in seasonal H1N1, but not in co-circulating H3N2 strains. This is the
      first report of genetic characterization of circulating Influenza A strains from
      India. The results also highlight the importance of continuing Influenza
      surveillance in developing countries of Asia for monitoring unusual strains with
      pandemic potential and mutations conferring antiviral resistance.

PMID- 20678591
TI  - Tolerogenic dendritic cells in autoimmune diseases: crucial players in induction
      and prevention of autoimmunity.
AB  - The immune system has evolved to coordinate responses against numerous invading
      pathogens and simultaneously remain silent facing self-antigens and those derived
      from commensal organisms. But, if both processes are not maintained in strict
      balance, a potential threat can emerge due to the risk of chronic inflammation
      and/or autoimmunity development. Therefore, there is a negative immune regulation
      where tolerogenic dendritic cells (tDCs) participate actively. Under steady-state
      conditions, tDC are notably involved in the elimination of autoreactive T cells
      at the thymus, and in the control of T cells specific to self and harmless
      antigens in the periphery. But in the presence of foreign antigens in an
      inflammatory milieu, dendritic cells (DCs) mature and induce T cells activation
      and their migration to B cell areas to assist in antibody production.
      Additionally, there are other factors such as infections, anti tumoral immune
      responses, trauma-mediated disruption, etc. that may induce alterations in the
      balance between tolerogenic and immunogenic functions of DCs and instigate the
      development of autoimmune diseases (ADs). Therefore, in recent years, DCs have
      emerged as therapeutic targets to control of ADs. Diverse strategies in vitro
      and/or in animal models of ADs have explored the tolerogenic functions of DCs and
      demonstrated their feasibility to prevent or control an autoimmune process, but
      still leaving a void in their application in clinical assays. The purpose of this
      paper is to give a general overview of the current literature on the significance
      of tDCs in tolerance maintenance to self and innocuous antigens, the most
      relevant alterations involved in the pathophysiology of ADs, the cellular and
      molecular mechanisms involved in their tolerogenic function and the current
      strategies used to exploit their tolerogenic potential.

PMID- 20678592
TI  - The effect of pharmacological therapy on the cardiovascular system of patients
      with systemic rheumatic diseases.
AB  - The higher mortality rate among rheumatoid arthritis (RA) patients in comparison
      with the general population is largely attributable to cardiovascular (CV)
      disease, particularly coronary atherosclerosis, but also non-fatal myocardial
      infarction and heart failure. It may be due to RA-specific risk factors such as
      hyperhomocysteinemia, disease-related dyslipidemia or vascular inflammation, or
      morbidity related to high levels of cytokines such as tumour necrosis factor
      (TNF) and RA medications. Non-steroidal anti-inflammatory drugs (NSAIDs) are
      among the most important in rheumatology, but many are associated with CV
      disease. A number of randomised control trials have shown that, although exposure
      to low doses of corticosteroids for 1-3years does not significantly increase CV
      risk, longer exposure can increase CV events. The use of disease-modifying
      antirheumatic drugs (DMARDs), particularly methotrexate, increases
      homocysteinemia, reduces inflammation and improves lipid profiles, thus reducing
      the development of atherosclerosis and clinically overt CVD. Although
      contraindicated in RA patients with severe heart failure, biological agents such
      as anti-TNF agents delay and even reverse the progression of endothelial
      dysfunction and atherosclerosis. Tocilizumab leads to changes in lipid profiles
      without increasing adverse vascular events. The effects on the CV system depend
      on the drug itself, the dose and the period of exposure, and so CV risk should be
      evaluated before starting treatment with any drug.

PMID- 20678593
TI  - Effects of treatment strategy on endothelial function.
AB  - A large body of evidence indicates that endothelial dysfunction is a
      characteristic of patients with arterial hypertension. As functional
      abnormalities lead to impaired endothelium-dependent vasodilation, this early
      step of atherogenesis is potentially reversible. In addition to reducing blood
      pressure, the major families of anti-hypertensive drugs have a number of
      pleiotropic effects that could improve endothelial function. In particular, the
      renin-angiotensin system plays an important role in the pathogenesis of both
      arterial hypertension and endothelial dysfunction, and so drugs capable of
      limiting the dangerous effects of this hormonal axis, such as angiotensin
      converting enzyme (ACE) inhibitors, angiotensin receptor blockers and renin
      inhibitors, could help prevent/delay/reverse the atherosclerotic process. New
      third-generation beta-blockers and 5-phosphodiesterase inhibitors may affect
      endothelial function. Furthermore, the HMGCoA-reductase inhibitors currently used
      to reduce cholesterol levels have major pleiotropic anti-inflammatory and anti
      hypertensive effects. The preservation or recovery of endothelial function in
      hypertensive patients is crucial to inhibit the development of atherosclerosis
      and the onset of cardiovascular events. This review focuses on the ancillary
      effects of hypertensive drugs and HMGCoA-reductase inhibitors that go beyond
      lowering blood pressure and cholesterol levels.

PMID- 20678594
TI  - Neuropilins and semaphorins - from angiogenesis to autoimmunity.
AB  - Angiogenesis, the growth of new blood vessels from preexisting ones, is an
      important process in health and disease. The persistence of neovascularization in
      inflammatory diseases, such as rheumatoid arthritis (RA), might facilitate the
      entrance of inflammatory cells into the synovium and stimulate pannus formation.
      Several potent pro-angiogenic cytokines have been implicated in inflammatory
      angiogenesis. Of these, vascular endothelial growth factor (VEGF) and its
      receptors (VEGFRs) have been demonstrated to play a central role in RA, systemic
      lupus erythematosus (SLE) and multiple sclerosis (MS). Increased serum levels of
      VEGF were found to correlate with disease activity and severity of these diseases
      whereas, remission was associated with decreased levels. In the last few years,
      other molecules, initially found in neurodevelopment, were found to be involved
      in angiogenesis and recently also in the immune system and autoimmunity.
      Neuropilins (NPs) are VEGF receptors, while some of the semaphorins (SEMAs) are
      neuropilins' ligands. Their involvement in the development of autoimmune diseases
      and the various mechanisms by which they may induce autoimmunity will be
      discussed in this review.

PMID- 20678595
TI  - From endothelial dysfunction to atherosclerosis.
AB  - It has recently emerged that endothelial dysfunction is an early step in the
      development of atherosclerosis and is mainly characterised by a reduction in the
      bioavailability of nitric oxide. All of the traditional cardiovascular (CV) risk
      factors (dyslipidemia, arterial hypertension, hyperglycemia and diabetes) are
      associated with endothelial dysfunction, and oxidised low-density lipoproteins,
      the renin-angiotensin axis and insulin resistance play important roles in the
      pathogenesis of impaired endothelial function. The increased expression of
      adhesion molecules and pro-inflammatory cytokines leads to abnormal endothelium
      dependent vasodilation which could be investigated using vasoreactivity tests
      such as flow-mediated dilation in the brachial artery. Recently, new evidences
      showed that the immune system plays an important role in the pathogenesis of
      endothelial dysfunction and atherosclerosis with a particular regard towards
      autoimmunity. The high prevalence of the atherosclerotic process in systemic
      autoimmune diseases supports the hypothesis of the immune pathogenesis.
      Evaluating coronary microvascular dysfunction by means of transthoracic
      echocardiography with non-invasive coronary flow reserve assessment is
      particularly interesting as it could detect preclinical impairment of coronary
      microvascular function. The discovery that the mechanisms responsible for
      endothelial damage have a genetic basis could improve the approach to CV
      diseases. This review summarises the most important aspects of the pathogenesis
      and development of endothelial dysfunction, with particular attention to the role
      of traditional CV risk factors, the usefulness of vasoreactivity tests, and the
      future perspectives opened by genetic studies.

PMID- 20678596
TI  - Does the use of transgenic plants diminish or promote biodiversity?
AB  - The protection of biodiversity and of ecosystem services ought to be a top
      priority, taken into consideration in the course of all human activities, because
      we depend on it fully now and for the future. In this context, we note that the
      ecological problems related to the cultivation of GE crops fail to differ in any
      fundamental way from the ecological problems associated with agriculture in
      general, except that they usually involve the application of much lower
      quantities of chemicals and thus tend to leave the environments in and adjacent
      to where they are grown in better condition than do the conventional ones. Higher
      productivity on cultivated lands, which is one outcome of growing GE crops,
      protects biodiversity by sparing lands not intensively cultivated, whereas
      relatively non-productive agriculture practised is highly destructive to
      biodiversity, since it consumes more land in an often destructive way, even
      though more biodiversity may be preserved among the crops themselves than in
      industrialized, large fields, especially if hedgerows and woodlands are not
      encouraged in near proximity. The major preservation of biodiversity, however,
      does not take place among crops! If weeds are present that are closely related to
      the crops, they may acquire immunity to the effects from which the crops were
      protected and be more difficult to control among them. The production of
      superweeds as a result of hybridization between cultivated crops and their wild
      relatives is essentially a myth. The definition of 'organic' production in the
      U.S. and elsewhere unjustifiably rules out GE crops, often in such a way as to
      damage the environment more than would be the case otherwise. Unless the
      definition of 'organic' is a problem, or close relatives to the crops are weedy
      among them, there seems to be essentially no ecological risk involved in growing
      GE crops.

PMID- 20678597
TI  - Fostering a new dialogue to improve access to finance for European biopharma
      SMEs.
AB  - This article reviews the current economic crisis as it impacts upon European
      biopharma SMEs and their ability to secure investment and funding. In particular
      it presents an analysis of a broader, pre-crisis structural problem in Europe
      related to the lack of institutional investors for Europe's life sciences venture
      capital funds and the impact this has both on the funds available for investment
      by VCs into Europe's biotech companies, and the effect on the type and stage of
      biopharma companies able to raise money. This article also presents an overview
      of an on-going stakeholder dialogue to address these issues and the proposals
      raised so far for possible solutions.

PMID- 20678598
TI  - Ginsenoside Rb1 and paeoniflorin inhibit transient receptor potential vanilloid-1
      activated IL-8 and PGE2 production in a human keratinocyte cell line HaCaT.
AB  - Ginsenoside Rb1 (GRb1) and paeoniflorin (PF) are active substances of Chinese
      traditional herbs and have been commonly used to treat skin inflammation
      diseases, but little is known about the mechanisms involved. In the present
      study, the effects of GRb1 and PF on the production of inflammatory mediators and
      the possible mechanisms of transient receptor potential vanilloid-1 (TRPV1) in
      these mediators induction were explored. It has been shown that GRb1 and PF
      inhibited the productions of IL-8 and PGE2 induced by capsaicin (CAP) in HaCaT
      cells and HEK 293T-TRPV1 cells (which were transgenic and overexpressed TRPV1)
      but had no effect on HEK 293T mock cells (p<0.05). Besides, CAP was able to
      induce calcium influx and nuclear factor kappa B(NF-kappaB) transcriptional
      activity in HaCaT cells and HEK 293T-TRPV1 cells, but had no effect on HEK 293T
      mock cells. Furthermore, GRb1 inhibited CAP-induced calcium influx and NF-kappaB
      transcriptional activity in both HaCaT cells and HEK 293T-TRPV1 cells. However,
      PF decreased CAP-induced calcium influx and NF-kappaB transcriptional activity
      only in HaCaT cells. This would suggest that GRb1 inhibits CAP-induced calcium
      influx and NF-kappaB activity through TRPV1 signal, while calcium influx and NF
      kappaB activity might not be involved in the inhibitory effect of PF on TRPV1
      signal. Furthermore, the inhibitory rates of GRb1 and PF on IL-8 and PGE2
      production were higher than those caused by capsazepine, an antagonist of TRPV1,
      suggesting that GRb1 and PF have great potential in clinical treatment of skin
      diseases.

PMID- 20678599
TI  - Surgical smoke evacuation guidelines: compliance among perioperative nurses.
AB  - More than 500,000 health care workers are exposed to surgical smoke every year.
      Toxic gases create an offensive odor, small particulate matter causes respiratory
      complications, and pathogens may be transmitted in the surgical smoke to the
      surgical team. Previous research notes that perioperative nurses do not
      consistently follow smoke evacuation recommendations. The purpose of this study
      was to determine key indicators that are associated with compliance with smoke
      evacuation recommendations. Data from a web-based survey completed by 777 nurse
      members of AORN were analyzed to examine the relationship between the key
      indicators and compliance with smoke evacuation recommendations. Major findings
      were that specific key indicators influencing compliance include increased
      knowledge and training, positive perceptions about the complexity of the
      recommendations, and increased specialization, interconnectedness, and leadership
      support in larger facilities. Education programs can be developed that directly
      address these key predictors so that a surgical environment free from surgical
      smoke is promoted.

PMID- 20678603
TI  - Compliance with surgical smoke evacuation guidelines: implications for practice.
AB  - Surgical smoke presents a serious health hazard, but perioperative nurses'
      compliance with smoke evacuation recommendations is not consistent. I
      investigated key indicators for compliance with electrosurgical smoke evacuation
      recommendations based on nurses' individual innovativeness characteristics,
      perceptions of the attributes of smoke evacuation recommendations, and
      organizational innovativeness characteristics. The study findings provide
      implications for improving nurses' compliance with smoke evacuation
      recommendations. Individual innovativeness characteristics, including nurses'
      knowledge and training, were most strongly linked to smoke evacuation compliance.
      The key indicators that promote surgical smoke evacuation can provide direction
      to guide the content of education programs and help identify the personnel and
      settings that are most in need of this information. Barriers to compliance
      included lack of equipment, physician resistance, noise, and staff member
      complacency. Vendor demonstrations on the ease of smoke evacuation device use can
      show nurses that smoke evacuation is compatible with nursing practice. Facility
      leaders should provide smoke evacuation policies that are easy to understand and
      should enforce these policies.

PMID- 20678604
TI  - The nurse liaison in perioperative services: a family-centered approach.
AB  - Surgery is a stressful time for patients, their family members, and their
      significant others. A perioperative nurse liaison can offer support, reinforce
      preoperative teaching, answer questions, and provide information during the
      surgical procedure that may help family members manage stress and view the
      process more positively. To provide the best possible care to patients and their
      family members, perioperative leaders at the Exempla Good Samaritan Hospital,
      Lafayette, Colorado, started a nurse liaison program when the facility opened in
      2004. Although OR nurses were the first choice for the position, the director of
      perioperative services soon found that postanesthesia care unit nurses were the
      best candidates for this role. Positive outcomes of the program have included
      letters from patients praising the nurse liaison, better informed patients, and
      less anxious family members. As a result of this program, the facility's patient
      satisfaction survey scores related to communication had a marked improvement by
      June 2009.

PMID- 20678605
TI  - The evolution of a surgical liaison program in a children's hospital.
AB  - Surgical liaison nurses use clear communication to provide timely reports to
      family members about their loved one during the time the patient is in the OR.
      The surgical liaison program at the Children's Hospital Boston, Massachusetts,
      has evolved over time. It began as nurses supervising brief family member visits
      to the postanesthesia care unit (PACU) and has become a program in which surgical
      liaison nurses work with OR and PACU staff members to access and provide patient
      specific information to families throughout the surgical time period and prepare
      families for extended visits to the PACU. In addition, we redesigned our surgical
      department by expanding its size, locating it closer to the OR and PACU, and
      providing more amenities to family members. A survey conducted to assess family
      member needs found that most people were satisfied with the services provided,
      and we were able to make improvements to services based on the survey feedback.

PMID- 20678606
TI  - Preventing surgically induced diabetes after total pancreatectomy via autologous
      islet cell reimplantation.
AB  - Total pancreatectomy may be the only treatment option that relieves pain and
      tissue destruction for patients with chronic pancreatitis, but this procedure
      causes surgically induced diabetes, which is difficult to manage because of the
      absence of insulin-producing beta cells. Some patients may benefit from
      autologous islet cell reimplantation, a procedure that involves collecting and
      purifying the islets of Langerhans from the patient's own resected pancreas and
      reinfusing them into the patient via the portal vein. Typically, candidates for
      this procedure are younger adults with nondilated pancreatitis that has yet to
      develop into glucose intolerance. Islet cell transplantation success varies and
      is directly related to the quality and quantity of the patient's pancreas and the
      damage caused by the chronic pancreatitis.

PMID- 20678607
TI  - The real costs of surgical instrument training in sterile processing revisited.
AB  - The need for properly trained sterile processing staff members has grown with the
      increased sophistication of surgical procedures. In 1998, I conducted a survey of
      hospitals about various aspects of training sterile processing personnel,
      including the length of time for training employees to process general surgical
      and specialty surgical instruments. To evaluate trends, I conducted a second
      survey 10 years later. A majority of the 2008 respondents indicated that training
      would take three to six months (60%) or six to 12 months (31%) and that most
      preceptors (52%) spend two to three months working with new employees. A
      calculation of the cost to train a sterile processing technician to the competent
      level, including the salary of the preceptor, was $41,414 for 2008, an increase
      of more than 100% from the 1998 calculation. These costs must be weighed against
      the loss of revenue when procedures are delayed because of missing, damaged, or
      unclean instruments and the patient safety issues that could result if an
      employee is not well trained.

PMID- 20678608
TI  - Determining the state of knowledge for implementing the universal protocol
      recommendations: an integrative review of the literature.
AB  - The purpose of this study was to determine the current state of knowledge
      concerning the implementation of the Joint Commission's Universal Protocol. We
      conducted an integrative review of the literature through a systematic search of
      the National Library of Medicine (ie, PubMed) database to identify empirical and
      theoretical documents that discussed the implementation process for the Universal
      Protocol. The current state of knowledge varies from facility to facility, and we
      noted significant trends, gaps, and areas of concern in the implementation
      process. Successful implementation of the Universal Protocol has the following
      elements: a multidisciplinary team approach, active staff/patient participation,
      supportive hospital administration/leadership, and active communication that
      promotes a healthy work environment.

PMID- 20678609
TI  - Nonpharmacological interventions for assisting the induction of anesthesia in
      children.

PMID- 20678610
TI  - Perioperative care of the patient with bipolar disorder.

PMID- 20678611
TI  - Structural empowerment: the magnet model applied to perioperative nursing.

PMID- 20678612
TI  - A comparison of the cultural values of Sweden to a patient safety culture.

PMID- 20678614
TI  - Radiation safety.

PMID- 20678616
TI  - Surprise wire.

PMID- 20678617
TI  - Ileoileal intussusception due to ileal ectopic pancreas with abundant fat tissue
      mimicking lipoma.
AB  - A 26-year-old woman presented with symptoms of bowel obstruction. An emergent
      computed tomography (CT) scan was performed which showed ileoileal
      intussusceptions due to a fatty nodule. Exploratory laparotomy and removal of the
      involved small bowel was performed. The pathology showed the leading point of the
      intussusception to be ectopic pancreas with abundant fatty infiltration.

PMID- 20678618
TI  - Racial disparities in motorcycle-related mortality: an analysis of the National
      Trauma Data Bank.
AB  - BACKGROUND: Studies have shown racial disparities in outcomes after motor vehicle
      crashes; however, it is currently unknown if race impacts the likelihood of
      mortality after a motorcycle crash (MCC). The primary objective of this study was
      to determine if race is associated with MCC mortality. METHODS: We performed a
      retrospective cross-sectional analysis of MCCs included in the National Trauma
      Data Bank between 2002 and 2006. Multiple logistic regression was used to adjust
      for age, sex, insurance status, year, helmet use, and injury severity
      characteristics. RESULTS: Black patients had a 1.58 (95% confidence interval,
      1.28-1.97) increased odds of mortality after a MCC, but were more likely to use a
      helmet (1.30; 95% confidence interval, 1.19-1.43) compared with their white
      counterparts (n = 62,840). CONCLUSIONS: Black motorcyclists appear more likely to
      die after a MCC compared with whites. Although the reasons for this disparity are
      unclear, these data suggest that resources beyond encouraging helmet use are
      necessary to reduce fatalities among black motorcyclists.

PMID- 20678619
TI  - Surgical treatment in Paget's disease of the breast.
AB  - BACKGROUND: The aim of this study was to evaluate the outcomes of surgical
      treatment of Paget's disease of the breast, with special emphasis on magnetic
      resonance imaging (MRI) and sentinel node biopsy (SNB). METHODS: The study
      included 58 consecutive patients with Paget's disease treated from 1995 to 2006.
      RESULTS: Twenty-five patients had ductal carcinoma in situ, and 31 had invasive
      carcinoma. MRI was performed in 14 patients, with positive findings in 7
      patients, 5 of whom had negative findings on conventional imaging. The overall
      mastectomy rate was 76%. Eighteen patients underwent SNB, and 26 patients
      underwent full or partial axillary clearance. Fourteen patients had no axillary
      surgery. One patient had local recurrence after breast conservation, and another
      had axillary recurrence after negative results on SNB. Six patients had distant
      metastases. Four patients died of breast cancer. CONCLUSIONS: Paget's disease is
      frequently associated with peripheral or multicentric cancer. MRI may be helpful
      when considering breast conservation or omitting axillary nodal staging.

PMID- 20678620
TI  - Indications and results for transduodenal sphincteroplasty in the era of
      endoscopic sphincterotomy.
AB  - BACKGROUND: Transduodenal sphincterotomy (TS) has fallen into disuse since
      endoscopists developed techniques to treat sphincter problems nonsurgically.
      However, some patients experience recurrent sphincter strictures after endoscopic
      sphincterotomy (ES), with the ampulla endoscopically inaccessible, and pancreas
      divisum (PD); these patients are referred to a surgeon because they are
      unsuitable for ES. METHODS: The medical records of patients who underwent TS at
      the First Department of Surgery of the Medical School, University of Rome "La
      Sapienza," between January 1997 and December 2005 were reviewed. A total of 82
      patients, including 47 women and 35 men with a mean age of 47 years (range, 26-67
      y), underwent TS in our unit in the aforementioned period. Previous unsuccessful
      endoscopic retrograde cholangiography and ES were the indications for TS in 44
      patients, and previous gastric surgery with duodenal bypass was the indication
      for TS in 21 patients. Five patients underwent TS because of a PD and 10 because
      of the intraoperative findings of daughter hydatid cysts in the common bile duct
      and of a wide communication between the cyst cavity and the intrahepatic biliary
      tree. Two patients were referred to our institution after a surgical papillotomy
      performed elsewhere. Symptoms included abdominal pain in 100% of patients, nausea
      and/or vomiting in 78% of patients, and referred back pain in 56% of patients.
      Acute pancreatitis was present in the history of 26 patients, including 23 with
      previous ES. All patients underwent TS. Sphincteroplasty of the accessory papilla
      was performed in all patients with PD. Cornerstones of a successful TS are
      depicted. RESULTS: Asymptomatic hyperamylasemia was observed in 37 patients, and
      cholangitis and pancreatitis, which was resolved with conservative management,
      occurred in 2 patients. One patient developed an intra-abdominal abscess that was
      treated with image-guided percutaneous drainage. No perioperative deaths occurred
      in this series. The mean length of follow-up evaluation was 84.4 months (range,
      16-115 mo). Good results were achieved in 53 patients (73.6%), fair results in 17
      patients (23.6%), and poor results in 2 patients (2.7%). Both patients with poor
      results required reoperation because of recurrent pancreatitis and pancreatic
      pseudocyst. CONCLUSIONS: TS still represents, although undoubtedly with updated
      indications compared with the past, a surgical procedure that must be up to date,
      ensuring absolutely satisfactory results.

PMID- 20678622
TI  - A compact portable flow analysis system for the rapid determination of total
      phosphorus in estuarine and marine waters.
AB  - The development and evaluation of a portable flow analysis system for the in situ
      determination of total phosphorus is described. The system has been designed with
      rapid underway monitoring in mind. The system employs an ultra-violet photo
      reactor and thermal heating for peroxodisulfate digestion of total phosphorus to
      orthophosphate, followed by spectrophotometric detection with a multi-reflective
      flow cell and low-power light emitting diode using the molybdenum blue method.
      Reagents are stored under gas pressure and delivered using software controlled
      miniature solenoid valves. The fully automated system has a throughput of 115
      measurements per hour, a detection limit of 1 microg PL(-1), and gives a linear
      response over the calibration range of 0-200 microg PL(-1) (r(2)=0.9998), with a
      precision of 4.6% RSD at 100 microg PL(-1) (n=10). Field validation of the
      instrument and method was performed in Port Philip and Western Port Bays in
      Victoria, SE Australia, where 2499 analyses were performed over a 25 h period,
      over a cruise path of 285 km. Good agreement was observed between determinations
      of samples taken manually and analysed in the laboratory and those measured in
      situ with the flow analysis system.

PMID- 20678621
TI  - Laparoscopic versus open mesh repair for recurrent inguinal hernia: a meta
      analysis of outcomes.
AB  - BACKGROUND: The objective of this study was to examine the outcomes of
      comparisons between laparoscopic and open mesh repairs in the setting of
      recurrent inguinal hernia. METHODS: The electronic databases MEDLINE, Embase,
      Pubmed, and the Cochrane Library were used to search for articles from 1990 to
      2008. The present meta-analysis pooled the effects of outcomes of a total of
      1,542 patients enrolled into 5 randomized controlled trials and 7 comparative
      studies, using classic and modern meta-analytic methods. RESULTS: Significantly
      fewer cases of hematoma/seroma formation were observed in the laparoscopic group
      in comparison with the Lichtenstein group (odds ratio, .38; .15-.96; P = .04). A
      matter of great importance is the higher relative risk of overall recurrence in
      the transabdominal preperitoneal group compared with the totally extraperitoneal
      group (relative risk, 3.25; 1.32-7.9; P = .01). CONCLUSIONS: Laparoscopic versus
      open mesh repair for recurrent inguinal hernia was equivalent in most of the
      analyzed outcomes.

PMID- 20678623
TI  - Tutorial on evaluation of type I and type II errors in chemical analyses: from
      the analytical detection to authentication of products and process control.
AB  - Uncertainty is inherent in all experimental determinations. Nevertheless, these
      measurements are used to make decisions including the performance of the own
      measurement systems. The link between the decision and the true implicit system
      that generates the data (measurement system, production process, category of
      samples, etc.) is a representation of this uncertainty as a probability
      distribution. This representation leads to the probabilistic formalization of the
      possibility of making errors. In the context of regulations established by
      official agencies, it is important to use these statistical decision methods in
      some cases because the own norm makes them mandatory and, in general, because
      this is the way of reasonably evaluating whether a working hypothesis is rejected
      on the basis of the experimental data. The aim of the present tutorial is to
      introduce some ideas and basic methods for the critical analysis of experimental
      data. With this goal, the basic elements of the Neyman-Pearson theory of
      hypothesis testing are formally introduced in connection with the common problems
      in chemical analysis and, if this is the case, their relation to the norms of
      regulatory agencies. The notion of decision with 'enough quality' is modelled
      when explicitly considering: (1) the null, H(0), and alternative, H(1),
      hypotheses. (2) The significance level of the test, which is the probability,
      alpha, of rejecting H(0) when it is true, and the power of the test, 1-beta, beta
      being the probability of accepting H(0) when it is false. (3) The difference
      between H(0) and H(1) that has to be detected with experimental data. (4) The
      needed sample size. These four concepts should be explicitly defined for each
      problem and, under the usual assumption of normal distribution of the data, the
      mathematical relations among these concepts are shown, which allow the analyst to
      design a decision rule with pre-set values of alpha and beta. To illustrate the
      unifying character of this inferential methodology, several situations are
      exposed along the tutorial: the design of a hypothesis test to decide on the
      performance characteristics of analytical methods, the capability of detection of
      both quantitative and qualitative analytical methods (including its
      generalization to the case of multivariate and/or multiway signals), the
      analytical sensitivity with multivariate signals, the class-modelling and the
      process control.

PMID- 20678624
TI  - Uranium determination using atomic spectrometric techniques: an overview.
AB  - This review focuses on the determination of uranium using spectroanalytical
      techniques that are aimed at total determination such as flame atomic absorption
      spectrometry (FAAS), electrothermal atomic absorption spectrometry (ETAAS),
      inductively coupled plasma optical emission spectrometry (ICP-OES); and
      inductively coupled plasma mass spectrometry (ICP-MS) that also enables the
      determination of uranium isotopes. The advantages and shortcomings related to
      interferences, precision, accuracy, sample type and equipment employed in the
      analysis are taken into account, as well as the complexity and costs (i.e.,
      acquisition, operation and maintenance) associated with each of the techniques.
      Strategies to improve their performance that employ separation and/or
      preconcentration steps are considered, with an emphasis given to solid-phase
      extraction because of its advantages compared to other preconcentration
      procedures.

PMID- 20678625
TI  - Magnetic solids in analytical chemistry: a review.
AB  - Magnetic solids are widely used in detection and analytical systems because of
      the performance advantages they offer compared to similar solids that lack
      magnetic properties. These solids can be used to pre-concentrate analytes and for
      the magnetic separation and molecular identification of biomolecules, and organic
      and inorganic species. Magnetic solid separation techniques also offer benefits
      over centrifugation, filtration, and solid-phase extraction. In this review, we
      describe the synthesis, characterization and applications of a series of solids
      including silica supports, carbon nanotubes, alumina, organic polymers and other
      materials, mostly containing magnetite or paramagnetic metals. Also addressed are
      the future perspectives of magnetic solid applications.

PMID- 20678626
TI  - Quantification of organic acids in beer by nuclear magnetic resonance (NMR)-based
      methods.
AB  - The organic acids present in beer provide important information on the product's
      quality and history, determining organoleptic properties and being useful
      indicators of fermentation performance. NMR spectroscopy may be used for rapid
      quantification of organic acids in beer and different NMR-based methodologies are
      hereby compared for the six main acids found in beer (acetic, citric, lactic,
      malic, pyruvic and succinic). The use of partial least squares (PLS) regression
      enables faster quantification, compared to traditional integration methods, and
      the performance of PLS models built using different reference methods (capillary
      electrophoresis (CE), both with direct and indirect UV detection, and enzymatic
      essays) was investigated. The best multivariate models were obtained using
      CE/indirect detection and enzymatic essays as reference and their response was
      compared with NMR integration, either using an internal reference or an
      electrical reference signal (Electronic REference To access In vivo
      Concentrations, ERETIC). NMR integration results generally agree with those
      obtained by PLS, with some overestimation for malic and pyruvic acids, probably
      due to peak overlap and subsequent integral errors, and an apparent relative
      underestimation for citric acid. Overall, these results make the PLS-NMR method
      an interesting choice for organic acid quantification in beer.

PMID- 20678627
TI  - Development of a sensitive and selective Riboflavin sensor based on carbon ionic
      liquid electrode.
AB  - The electrochemical properties of Riboflavin adsorbed on carbon ionic liquid
      electrode (CILE) were studied by cyclic voltammetry. A film with a surface
      coverage of up to 3.3x10(-9) mol cm(-2) was formed after 10 min exposure time.
      Electron transfer coefficient and rate constant of electron transfer across the
      modified electrode were found to be 0.43 and 3.03 s(-1), respectively.
      Differential pulse voltammetry was used for the determination of Riboflavin. Two
      linear working ranges of 0.8-110 nM and 0.11-1.0 microM were obtained with
      correlation coefficients of 0.998 and 0.996, respectively. The experimental
      detection limit was obtained as 0.1 nM. The relative standard deviation for five
      replicate analyses was 4.7%. Other soluble vitamins had no significant
      interferences and the electrode was used for the determination of Riboflavin in
      pharmaceutical products, nutrition and beverages.

PMID- 20678628
TI  - Ultra-sensitive voltammetric sensor for trace analysis of carbamazepine.
AB  - A multi-walled carbon nanotubes (MWCNTs) film-coated glassy carbon electrode
      (GCE) was used for the voltammetric determination of carbamazepine (CBZ). The
      results showed that this simple modified electrode exhibited excellent
      electrocatalytic activity towards the oxidation of CBZ. The voltammetric response
      of CBZ at this film-modified electrode increased significantly when compared with
      that at a bare glassy carbon electrode and the sensor response was reproducible.
      The proposed method was applied to the quantification of CBZ in wastewater
      samples, collected in a municipal wastewater treatment plant, and in
      pharmaceutical formulations. The developed methodology yields results in accord
      with those obtained by chromatographic techniques commonly used in the
      quantification of pharmaceutical compounds in real samples. Good recoveries have
      been obtained and the limits of detection and quantification (40 and 140 nM,
      respectively) are among the lowest that have been reported to date for this
      pharmaceutical compound using voltammetric techniques.

PMID- 20678629
TI  - Molecularly imprinted polymer layer-coated silica nanoparticles toward dispersive
      solid-phase extraction of trace sulfonylurea herbicides from soil and crop
      samples.
AB  - This paper reports the preparation of metsulfuron-methyl (MSM) imprinted polymer
      layer-coated silica nanoparticles toward analysis of trace sulfonylurea
      herbicides in complicated matrices. To induce the selective occurrence of surface
      polymerization, the polymerizable double bonds were first grafted at the surface
      of silica nanoparticles by the silylation. Afterwards, the MSM templates were
      imprinted into the polymer-coating layer through the interaction with functional
      monomers. The programmed heating led to the formation of uniform MSM-imprinted
      polymer layer with controllable thickness, and further improved the
      reproducibility of rebinding capacity. After removal of templates, recognition
      sites of MSM were exposed in the polymer layers. As a result, the maximum
      rebinding capacity was achieved with the use of optimal grafting ratio. There was
      also evidence indicating that the MSM-imprinted polymer nanoparticles compared
      with nonimprinted polymer nanoparticles had a higher selectivity and affinity to
      four structure-like sulfonylurea herbicides. Moreover, using the imprinted
      particles as dispersive solid-phase extraction (DSPE) materials, the recoveries
      of four sulfonylurea herbicides determined by high-performance liquid
      chromatography (HPLC) were 80.2-99.5%, 83.8-102.4%, 77.8-93.3%, and 73.8-110.8%
      in the spiked soil, rice, soybean, and corn samples, respectively. These results
      show the possibility that the highly selective separation and enrichment of trace
      sulfonylurea herbicides from soil and crop samples can be achieved by the
      molecular imprinting modification at the surface of silica nanoparticles.

PMID- 20678630
TI  - Dispersive liquid-liquid microextraction based on the solidification of floating
      organic droplet for the determination of polychlorinated biphenyls in aqueous
      samples.
AB  - In the proposed method, an extraction solvent with a lower toxicity and density
      than the solvents typically used in dispersive liquid-liquid microextraction was
      used to extract seven polychlorinated biphenyls (PCBs) from aqueous samples. Due
      to the density and melting point of the extraction solvent, the extract which
      forms a layer on top of aqueous sample can be collected by solidifying it at low
      temperatures, which form a layer on top of the aqueous sample. Furthermore, the
      solidified phase can be easily removed from the aqueous phase. Based on
      preliminary studies, 1-undecanol was selected as the extraction solvent, and a
      series of parameters that affect the extraction efficiency were systematically
      investigated. Under the optimized conditions, enrichment factors for PCBs ranged
      between 494 and 606. Based on a signal-to-noise ratio of 3, the limit of
      detection for the method ranged between 3.3 and 5.4 ng L(-1). Good linearity,
      reproducibility and recovery were also obtained.

PMID- 20678631
TI  - Application of dispersive liquid-liquid microextraction and spectrophotometric
      detection to the rapid determination of rhodamine 6G in industrial effluents.
AB  - A rapid and effective preconcentration method for extraction of rhodamine 6G was
      developed by using a dispersive liquid-liquid microextraction (DLLME) prior to UV
      vis spectrophotometry. In this extraction method, a suitable mixture of acetone
      (disperser solvent) and chloroform (extractant solvent) was injected rapidly into
      a conical test tube containing aqueous solution of rhodamine 6G. Therefore, a
      cloudy solution was formed. After centrifugation of the cloudy solution,
      sedimented phase was evaporated, reconstituted with methanol and measured by UV
      vis spectrophotometry. Different operating variables such as type and volume of
      extractant solvent, type and volume of disperser solvent, pH of the sample
      solution, salt concentration and extraction time were investigated. The optimized
      conditions (extractant solvent: 300 microL of chloroform, disperser solvent: 3 mL
      of acetone, pH: 8 and without salt addition) resulted in a linear calibration
      graph in the range of 5-900 ng mL(-1) of rhodamine 6G in initial solution with
      R(2)=0.9988 (n=5). The Limits of detection and quantification were 2.39 and 7.97
      ng mL(-1), respectively. The relative standard deviation for 50 and 250 ng mL(-1)
      of rhodamine 6G in water were 2.88% and 1.47% (n=5), respectively. Finally, the
      DLLME method was applied for determination of rhodamine 6G in different
      industrial waste waters.

PMID- 20678632
TI  - Extraction and separation of a lysine-rich protein by formation of supramolecule
      between crown ether and protein in aqueous two-phase system.
AB  - The macrocyclic calixarenes and crown ethers have recently been found to form
      hydrophobic complexes with the cationic protein cytochrome c (Cyt-c), by
      recognizing lysine residues on the protein surface. In the present study, it was
      found that the distribution of cytochrome c in Li(2)SO(4)/PEG aqueous two-phase
      system (ATPS) can be controlled by complexation with the crown ether
      dicyclohexano-18-crown-6 (DCH18C6). The protein was quantitatively extracted into
      the PEG-rich phase in the presence of DCH18C6 and perchlorate ion. Of various
      crown ethers and their analogues that were investigated, only DCH18C6 was able to
      extract cytochrome c into the PEG-rich phase. Extraction of cytochrome c in the
      ATPS using DCH18C6 is complete within 5 min. Cytochrome c complexed with DCH18C6
      in the PEG-rich phase was quantitatively recovered into a salt-rich phase using
      K(2)SO(4) by ion exchange of potassium ion and cationic protein in the cationic
      protein complex with DCH18C6. Selective extraction of cationic proteins was
      demonstrated in the ATPS. Under optimum conditions, the lysine-rich protein
      cytochrome c was selectively extracted over other cationic proteins using
      DCH18C6.

PMID- 20678633
TI  - Infrared chemical imaging: spatial resolution evaluation and super-resolution
      concept.
AB  - Chemical imaging systems help to solve many challenges in various scientific
      fields. Able to deliver rapid spatial and chemical information, modern infrared
      spectrometers using Focal Plane Array detectors (FPA) are of great interest.
      Considering conventional infrared spectrometers with a single element detector,
      we can consider that the diffraction-limited spatial resolution is more or less
      equal to the wavelength of the light (i.e. 2.5-25 microm). Unfortunately, the
      spatial resolution of FPA spectroscopic setup is even lower due to the detector
      pixel size. This becomes a real constraint when micron-sized samples are
      analysed. New chemometrics methods are thus of great interest to overcome such
      resolution drawback, while keeping our far-field infrared imaging spectrometers.
      The aim of the present work is to evaluate the super-resolution concept in order
      to increase the spatial resolution of infrared imaging spectrometers using FPA
      detectors. The main idea of super-resolution is the fusion of several low
      resolution images of the same sample to obtain a higher-resolution image.
      Applying the super-resolution concept on a relatively low number of FPA
      acquisitions, it was possible to observe a 30% decrease in spatial resolution.

PMID- 20678634
TI  - Use of multiple colorimetric indicators for paper-based microfluidic devices.
AB  - We report here the use of multiple indicators for a single analyte for paper
      based microfluidic devices (microPAD) in an effort to improve the ability to
      visually discriminate between analyte concentrations. In existing microPADs, a
      single dye system is used for the measurement of a single analyte. In our
      approach, devices are designed to simultaneously quantify analytes using multiple
      indicators for each analyte improving the accuracy of the assay. The use of
      multiple indicators for a single analyte allows for different indicator colors to
      be generated at different analyte concentration ranges as well as increasing the
      ability to better visually discriminate colors. The principle of our devices is
      based on the oxidation of indicators by hydrogen peroxide produced by oxidase
      enzymes specific for each analyte. Each indicator reacts at different peroxide
      concentrations and therefore analyte concentrations, giving an extended range of
      operation. To demonstrate the utility of our approach, the mixture of 4
      aminoantipyrine and 3,5-dichloro-2-hydroxy-benzenesulfonic acid, o-dianisidine
      dihydrochloride, potassium iodide, acid black, and acid yellow were chosen as the
      indicators for simultaneous semi-quantitative measurement of glucose, lactate,
      and uric acid on a microPAD. Our approach was successfully applied to quantify
      glucose (0.5-20 mM), lactate (1-25 mM), and uric acid (0.1-7 mM) in clinically
      relevant ranges. The determination of glucose, lactate, and uric acid in control
      serum and urine samples was also performed to demonstrate the applicability of
      this device for biological sample analysis. Finally results for the multi
      indicator and single indicator system were compared using untrained readers to
      demonstrate the improvements in accuracy achieved with the new system.

PMID- 20678635
TI  - A novel and specific fluorescence reaction for uracil.
AB  - Facile and specific methods to quantify a nucleobase in biological samples are of
      great importance for diagnosing disorders in nucleic acid metabolism. In the
      present study, a novel fluorogenic reaction specific for uracil has been
      developed. The reaction was carried out in an alkaline medium containing
      benzamidoxime and K(3)[Fe(CN)(6)] which were heated for 2.0 min. Under the
      optimum reaction conditions, strong fluorescence was produced only from uracil,
      not from other many biogenic compounds tested such as cytosine, thymine, adenine,
      guanine, nucleobases, nucleosides, nucleotides, amino acids, saccharides,
      creatine, creatinine and urea. The sensitivity of this method was compared with a
      known fluorogenic reaction using phenacylbromide which does not react with uracil
      but reacts with cytosine, adenine and their analogues. The proposed uracil
      specific reaction showed approximately 400-fold higher sensitivity than the
      phenacylbromide reaction. The lower detection limit of uracil by the present
      method was 100 pmol mL(-1), and a good linearity of the calibration curve was
      obtained up to 100 nmol mL(-1) uracil. Due to its high sensitivity and
      specificity, the quantitative determination of uracil was possible by the
      proposed fluorimetric method.

PMID- 20678636
TI  - Determination of glutathione content in grape juice and wine by high-performance
      liquid chromatography with fluorescence detection.
AB  - A modified preparation of sample was developed for the determination of
      glutathione content in grape juice and wine by high-performance liquid
      chromatography with fluorescence detection, using on-line pre-column
      derivatization. Ice-cold deoxygenated methanol was used to deactivate the
      oxidation enzymes in juices or wines and keep the glutathione stable. The optimum
      recovery of glutathione content in grape juice and wine was obtained when either
      the sample of grape juice or wine was mixed in ice-cold deoxygenated methanol in
      the ratio 10:90 (v:v) and further diluted in sodium acetate buffer in the ratio
      1:1 (v:v). The optimized method was validated for linearity, limit of detection,
      limit of quantification, precision and uncertainty. According to the validation
      data the method is appropriate for the determination of glutathione content in
      grape juice and wine. Glutathione contents in grape juices made from White Muscat
      grapes and Sauvignon Blanc wines were analysed. The average glutathione content
      in 28 young Sauvignon Blanc wines was 12.5 mg L(-1).

PMID- 20678637
TI  - Polymeric ionic liquid as a dynamic coating additive for separation of basic
      proteins by capillary electrophoresis.
AB  - A simple and economical capillary electrophoresis method has been developed for
      the analysis of four model basic proteins by employing a polymeric ionic liquid
      (PIL), poly(1-vinyl-3-butylimidazolium) bromide, as the dynamic coating additive.
      When a small amount of PIL was present in the background electrolyte, a cationic
      coating on the inner surface of fused-silica capillary was established. These PIL
      modified capillaries not only generated a stable reversed electroosmotic flow,
      but also effectively eliminated the wall adsorption of proteins. Several
      important parameters such as the PIL concentration in the background electrolyte,
      pH values and concentrations of the background electrolyte were optimized to
      improve the separation of basic proteins. Consequently, under the optimum
      conditions, a satisfied separation of basic proteins with peak efficiencies
      ranging from 247,000 to 540,000 (plates m(-1)) had been accomplished within 11
      min. The run-to-run RSDs (n=3) of the migration times for the four basic proteins
      were all less than 0.37%.

PMID- 20678638
TI  - Enantioselective analysis of ofloxacin and ornidazole in pharmaceutical
      formulations by capillary electrophoresis using single chiral selector and
      computational calculation of their inclusion complexes.
AB  - A capillary electrophoretic method for the separation of the enantiomers of both
      ofloxacin and ornidazole is described. Several parameters affecting the
      separation were studied, including the type and concentration of chiral selector,
      buffer pH, voltage and temperature. Good chiral separation of the racemic
      mixtures was achieved in less than 16 min with resolution factors Rs=5.45 and
      6.28 for ofloxacin and ornidazole enantiomers, respectively. Separation was
      conducted using a bare fused-silica capillary and a background electrolyte (BGE)
      of 50 mM H(3)PO(4)-1 M tris solution; pH 1.85; containing 30 mg mL(-1) of
      sulfated-beta-cyclodextrin (S-beta-CD). The separation was carried out in
      reversed polarity mode at 25 degrees C, 18 kV, detection wavelength at 230 nm and
      using hydrodynamic injection for 15 s. Acceptable validation criteria for
      selectivity, linearity, precision, and accuracy were studied. The limits of
      detection (LOD) and limits of quantitation (LOQ) of the enantiomers (ofloxacin
      enantiomer 1 (OF-E1), ofloxacin enantiomer 2 (OF-E2), ornidazole enantiomer 1 (OR
      E1) and ornidazole enantiomer 2 (OR-E2)) were (0.52, 0.46, 0.54, 0.89) and (1.59,
      1.40, 3.07, 2.70) microg mL(-1), respectively. The proposed method was
      successfully applied to the assay of enantiomers of both ofloxacin and ornidazole
      in pharmaceutical formulations. The computational calculations for the
      enantiomeric inclusion complexes rationalized the reasons for the different
      migration times between the ofloxacin and ornidazole enantiomers.

PMID- 20678639
TI  - Quantitative gold nanoparticle analysis methods: A review.
AB  - Research and development in the area of gold nanoparticles' (AuNPs) preparation,
      characterization, and applications are burgeoning in recent years. Many of the
      techniques and protocols are very mature, but two major concerns are with the
      mass domestic production and the consumption of AuNP based products. First, how
      many AuNPs exist in a dispersion? Second, where are the AuNPs after digestion by
      the environment and how many are there? To answer these two questions, reliable
      and reproducible methods are needed to analyze the existence and the population
      of AuNP in samples. This review summarized the most recent chemical and particle
      quantitative analysis methods that have been used to characterize the
      concentration (in number of moles of gold per liter) or population (in number of
      particles per mL) of AuNPs. The methods summarized in this review include, mass
      spectroscopy, electroanalytical methods, spectroscopic methods, and particle
      counting methods. These methods may count the number of AuNP directly or analyze
      the total concentration of element gold in an AuNP dispersion.

PMID- 20678640
TI  - Titania nanowires as substrates for sensing and photocatalysis of common textile
      industry effluents.
AB  - Sensing and photocatalysis of textile industry effluents such as dyes using
      mesoporous anatase titania nanowires are discussed here. Spectroscopic
      investigations show that the titania nanowires preferentially sense cationic
      (e.g. Methylene Blue, Rhodamine B) over anionic (e.g. Orange G, Remazol Brilliant
      Blue R) dyes. The adsorbed dye concentration on titania nanowires increased with
      increase in nanowire dimensions and dye solution pH. Electrochemical sensing
      directly corroborated spectroscopic findings. Electrochemical detection
      sensitivity for Methylene Blue increased by more than two times in magnitude with
      tripling of nanowire average length. Photodegradation of Methylene Blue using
      titania nanowires is also more efficient than the commercial P25-TiO(2)
      nanopowders. Keeping illumination protocol and observation times constant, the
      Methylene Blue concentration in solution decreased by only 50% in case of P25
      TiO(2) nanoparticles compared to a 100% decrease for titania nanowires.
      Photodegradation was also found to be function of exposure times and dye solution
      pH. Excellent sensing ability and photocatalytic activity of the titania
      nanowires is attributed to increased effective reaction area of the controlled
      nanostructured morphology.

PMID- 20678641
TI  - Use of Gemini surfactant in a one-step ellagic acid assay by resonance light
      scattering technique.
AB  - Ellagic acid (EA) reacted with Gemini zwitterionic surfactant, phosphodiesters
      quaternary ammonium salt (PQAS), and formed fine particles which produced strong
      enhancement in intensity of resonance light scattering (RLS). The effects of
      several factors on the RLS signal, such as pH, ionic strength, PQAS concentration
      and so on, were optimized. The relationship between enhanced RLS intensity and EA
      concentration was constructed. A novel and rapid method for the determination of
      EA was built. The linear range of this method was 0.016-4.0 microg mL(-1) and the
      detection limit was 13.9 ng mL(-1). Under the optimum conditions, the proposed
      method was applied to determine EA in body fluids with the results of
      quantitative recoveries between 98.4-101.4% in human serum samples and 99.1-102%
      in human urine samples. This method characterized by low limit detection is very
      sensitive and the cost is low, and constitutes a fast one-step procedure which
      requires only measuring the RLS intensities. The mechanism of the reaction was
      also studied. This investigation could contribute to the research on the delivery
      and release of bioactive molecules by Gemini surfactants.

PMID- 20678642
TI  - 2D spatiotemporal visualization system of expired gaseous ethanol after oral
      administration for real-time illustrated analysis of alcohol metabolism.
AB  - A novel 2-dimensional spatiotemporal visualization system of expired gaseous
      ethanol after oral administration for real-time illustrated analysis of alcohol
      metabolism has been developed, which employed a low level light CCD camera to
      detect chemiluminescence (CL) generated by catalytic reactions of standard
      gaseous ethanol and expired gaseous ethanol after oral administration. First, the
      optimization of the substrates for visualization and the concentration of luminol
      solution for CL were investigated. The cotton mesh and 5.0 mmol L(-1) luminol
      solution were selected for further investigations and this system is useful for
      0.1-20.0 mmol L(-1) of H(2)O(2) solution. Then, the effect of pH condition of
      Tris-HCl buffer solution was also evaluated with CL intensity and under the Tris
      HCl buffer solution pH 10.1, a wide calibration range of standard gaseous ethanol
      (30-400 ppm) was obtained. Finally, expired air of 5 healthy volunteers after
      oral administration was measured at 15, 30, 45, 60, 75, 90, 105 and 120 min after
      oral administration, and this system showed a good sensitivity on expired gaseous
      ethanol for alcohol metabolism. The peaks of expired gaseous ethanol
      concentration appeared within 30 min after oral administration. During the 30 min
      after oral administration, the time variation profile based on mean values showed
      the absorption and distribution function, and the values onward showed the
      elimination function. The absorption and distribution of expired gaseous ethanol
      in 5 healthy volunteers following first-order absorption process were faster than
      the elimination process, which proves efficacious of this system for described
      alcohol metabolism in healthy volunteers. This system is expected to be used as a
      non-invasive method to detect VOCs as well as several other drugs in expired air
      for clinical purpose.

PMID- 20678643
TI  - QCM DNA biosensor for the diagnosis of a fish pathogenic virus VHSV.
AB  - Viral haemorrhagic septicaemia (VHS) is one of the most serious viral diseases
      damaging both fresh and marine fish species. VHS caused by VHSV and diagnosis of
      VHSV has been dependent on the conventional methods, such as cell culture and RT
      PCR, which takes a few days or several hours. This study demonstrates a rapid and
      sensitive QCM biosensor for diagnosis of VHSV infection in fish. The QCM
      biosensor was developed to detect a main viral RNA encoding G protein in VHSV
      using the specific DNA probe. To maximize the sensitivity of the biosensor, we
      prepared three different DNA probes which modified 3' end of DNA by thiol, amine,
      or biotin and compared three different immobilisation methods on quartz surface
      coated with gold: immobilisation of thiol labelled probe DNA on naked gold
      surface, immobilisation of amino labelled probe DNA on gold surface prepared as
      carboxyl chip using MPA followed by EDC/NHS activation, and immobilisation of
      biotin labelled probe DNA on gold surface after immobilising avidin on carboxyl
      chip prior to biotin. As a result, immobilisation method using avidin-biotin
      interaction was most efficient to immobilise probe DNA and to detect target DNA.
      The QCM biosensor system using biotinylated probe DNA was stable enough to
      withstand 32 times of repeated regenerations and the detection limit was
      0.0016muM. Diagnosis using the QCM biosensor system was more sensitive and much
      faster than a conventional RT-PCR analysis in detecting the viral RNA.

PMID- 20678644
TI  - Investigation of plasma-functionalized multiwalled carbon nanotube film and its
      application of DNA sensor for Legionella pneumophila detection.
AB  - A novel multiwall carbon nanotube (MWCNT) electrode functionalized with oxygen
      plasma treatment was prepared and characterized, and its DNA sensing ability for
      Legionella pneumophila (L. pneumophila) detection was examined using
      electrochemical measurement. A well-patterned MWCNT working electrode (WE) on a
      Pt track was fabricated using photolithography, transfer methods and an etching
      technique. The MWCNT WE was functionalized by oxygen plasma treatment prior to
      applying for DNA sensor. The surface morphology of the plasma-functionalized
      MWCNT (pf-MWCNT) WEs were observed by scanning electron microscope (SEM) and the
      change of chemical composition was characterized by X-ray photoelectron
      spectroscopy (XPS), and electrochemical measurements were performed using CV with
      ferricyanide/ferrocyanide redox couple. Effective areas of working electrodes
      were calculated to be 0.00453 cm(2) for pristine MWCNT electrode and 0.00747
      0.00874 cm(2) for pf-MWCNT electrodes with different plasma treatment times.
      Differential pulse voltammetry (DPV) was carried out in methylene blue solution
      for DNA sensing. The pf-MWCNT based DNA sensor was successfully operated in a
      target concentration range of 10 pM to 100 nM and had a lower detection limit
      than a pristine MWCNT based DNA sensor.

PMID- 20678645
TI  - The potential of autofluorescence spectroscopy to detect human urinary tract
      infection.
AB  - Urinary tract infections (UTIs) are known to alter the normal urine composition
      which, in principle, can lead to changes in urine autofluorescence. This paper
      describes the study of human urine (normal and UTI) by using UV fluorescence
      excitation/emission matrices and synchronous spectra and proposes a method of
      diagnosing UTI without any sample preparation. The method is based on excitation
      in the shorter UV region (250-350 nm) which shows good discrimination between the
      normal urine and UTI samples. The synchronous scans with an offset of
      Deltalambda=90 nm were also able to differentiate between normal urines and UTI
      samples. These differences were observed even though the two known major urine
      fluorophores, tryptophan and indoxyl sulfate were present in the normal urine and
      UTI samples in similar concentration as established by HPLC analysis. Although
      the identity of substances responsible for the altered autofluorescence in UTI is
      not established, our study shows that autofluorescence has the potential to
      differentiate between normal human urine samples and those with UTI.

PMID- 20678646
TI  - Development and validation of a stability-indicative agar diffusion assay to
      determine the potency of linezolid in tablets in the presence of photodegradation
      products.
AB  - Linezolid (LNZ) is one of the first commercially available (and most widely used)
      oxazolidinone antibiotics. This study describes the development and validation of
      a microbiological assay, applying the cylinder-plate method, for the
      determination of the antibiotic linezolid, as well as the evaluation of the
      ability of the method in determining the stability of linezolid in tablets. The
      validation method yielded good results and included linearity, precision,
      accuracy, robustness and selectivity. The assay is based on the inhibitory effect
      of LNZ upon the strain of Bacillus subtilis ATCC 9372 used as the test
      microorganism. The results of the assay were treated statistically by analysis of
      variance (ANOVA) and were found to be linear (r(2)=0.9998) in the range of 20-80
      microg mL(-1), precise (inter-assay: R.S.D.=0.61) and accurate (R.S.D.=1.7). The
      method developed and validated proved to be indicative of stability and capable
      of determining the decay of linezolid in the presence of photodegradation
      products. Comparison of bioassay and liquid chromatography by ANOVA showed no
      significant difference between methodologies. The results demonstrated the
      validity of the proposed bioassay, which is a simple and useful alternative
      methodology for LNZ determination in routine quality control.

PMID- 20678647
TI  - Evaluation of performance of three different hybrid mesoporous solids based on
      silica for preconcentration purposes in analytical chemistry: From the study of
      sorption features to the determination of elements of group IB.
AB  - Several studies involving the physicochemical interaction of three silica based
      hybrid mesoporous materials with metal ions of the group IB have been performed
      in order to employ them for preconcentration purposes in the determination of
      traces of Cu(II), Ag(I) and Au(III). The three solids were obtained from
      mesoporous silica functionalized with 3-aminopropyl (APS), 3-mercaptopropyl (MPS)
      and N-[2-aminoethyl]-3-aminopropyl (NN) groups, respectively. Adsorption
      capacities for Au, Cu and Ag were calculated using Langmuir's isotherm model and
      then, the optimal values for the retention of each element onto each one of the
      solids were found. Physicochemical data obtained under thermodynamic equilibrium
      and under kinetic conditions - imposed by flow through experiments - allowed the
      design of simple analytical methodologies where the solids were employed as
      fillings of microcolumns held in continuous systems coupled on-line to an atomic
      absorption spectrometry. In order to control the interaction between the filling
      and the analyte at short times (flow through conditions) and thus, its effect on
      the analytical signal and the presence of interferences, the initial adsorption
      velocities were calculated using the pseudo second order model. All these
      experiments allowed the comparison of the solids in terms of their analytical
      behaviour at the moment of facing the determination of the three elements. Under
      optimized conditions mainly given by the features of the filling, the analytical
      methodologies developed in this work showed excellent performances with limits of
      detection of 0.14, 0.02 and 0.025 microg L(-1) and RSD % values of 3.4, 2.7 and
      3.1 for Au, Cu and Ag, respectively. A full discussion of the main findings on
      the interaction metal ions/fillings will be provided. The analytical results for
      the determination of the three metals will be also presented.

PMID- 20678648
TI  - SIA system employing the transient response from a potentiometric sensor array-
      Correction of a saline matrix effect.
AB  - A Sequential Injection Analysis (SIA) system and an 8-potentiometric all-solid
      state sensor array were coupled in a simple and automated electronic tongue
      device. The potentiometric sensors used were planar microfabricated structures
      with standard PVC membranes deposited onto a gold contact. The SIA system
      permitted the automated operation and generation of the calibration data, needed
      to build an Artificial Neural Network model, thanks to the precise dosing and
      mixing of volumes of stock solutions. The resolution of a four-ion mixture, i.e.
      ammonium, sodium, nitrate and chloride was the study case used for
      characterization of the system. Two different variants for signal acquisition,
      steady-state and transient recording, were arranged and compared. The dynamic
      treatment is shown to offer improved performance thanks to the benefits of the
      kinetic resolution. For this, it first extracts meaningful data from a FFT
      transform of each sensor's transient, which is then fed to an ANN model for
      estimation of each concentration in the four-ion mixture. While in a standard
      laboratory situation there was no difference between the two approaches, the
      dynamic treatment allowed the correction of a matrix effect in the case study,
      where an uncontrolled saline effect could be counterbalanced.

PMID- 20678649
TI  - New use of polypyrrole-chloride for selective preconcentration of copper prior to
      its determination of flame atomic absorption spectrometry.
AB  - Polypyrrole-chloride was studied as a new sorbent for preconcentration of
      copper(II) using solid-phase extraction prior to determination by flame atomic
      absorption spectrometry. The sorbent showed an extremely high selectivity towards
      copper(II) as an anionic chelate, i.e. Cu (pyrocatechol violet)(2)(2-) in the pH
      range of 4-7. Copper(II) as Cu (pyrocatechol violet)(2)(2-) was selectively
      retained on a column containing 1.0 g of polypyrrole-chloride and quantitatively
      eluted by 3 mL of 2.0 mol L(-1) nitric acid. The calibration graph was linear
      with a correlation coefficient of 0.999 at levels near the detection limit and up
      to at least 50 microg L(-1). When applied for preconcentration and determination
      of copper in tap water, waste water and hot spring water, the recoveries were
      found to be 96, 101 and 95%, respectively, with high precision (% relative
      standard deviation <4%) and low detection limit (0.87 microg L(-1)). Verification
      of the accuracy was carried out by the analysis of a standard reference material
      (BCR 715 wastewater-SRM). The relative error was +3.33%. The proposed method was
      successfully applied to the determination of copper in tap water, waste water and
      hot spring water samples.

PMID- 20678650
TI  - Rapid high-performance liquid chromatography-tandem mass spectrometry method for
      determination of pentoxifylline and its active metabolites M1 and M5 in human
      plasma and its application in bioavailability study.
AB  - A new rapid, sensitive and selective liquid chromatography coupled with mass
      spectrometry method was developed and validated for the simultaneous
      quantification of pentoxifylline (PTX) and two major active metabolites in human
      plasma (M1 and M5). After a deproteinization step, chromatographic separation of
      the selected analytes was performed on a RP-C18 column. The detection of target
      compounds was in multiple reaction monitoring mode using an ion trap mass
      spectrometer equipped with an electrospray ion source. The method was validated
      and proved to be linear, accurate and precise over the range 5.08-406.14, 10.08
      806.40 and 20.15-1611.60 ng/mL in case of PTX, M1 and M5, respectively. The major
      advantages of this method are the small sample volume, simple sample processing
      technique, the high sensitivity and the very good selectivity guaranteed by the
      MS/MS (in case of PTX) or MS/MS/MS (in case of M1 and M5) detection. The
      validated method has been successfully applied to a bioequivalence study.

PMID- 20678651
TI  - An in-tube SPME device for the selective determination of chlorophyll a in
      aquatic systems.
AB  - We report a new device for the estimation of the content of chlorophyll a pigment
      in water samples as an indicator of water quality. The extraction of the pigment
      from water was also optimized. 10 mL of water was filtered through a nylon filter
      (45 microm pore size and 13 mm of diameter), after the chlorophylls were
      dissolved by immersing the filter in 1 mL of a low non-hazardous solvent as
      ethanol. An in-valve in-tube SPME device coupled to capillary liquid
      chromatography with diode array detection was designed. A capillary column of 70
      cm in length (0.32 mm i.d. coated with 5% diphenyl-95% polydimethylsiloxane, 3
      microm coating thickness) was used as the loop of the injection valve for
      preconcentration and a Zorbax SB C(18) (SiO(2)-based) 150 mm x 0.5 mm i.d., 5
      microm column (Agilent) was used as analytical column. The achieved detection
      limit was 0.05 microg L(-1) and the working range of concentrations was 0.1-1
      microg L(-1). % RSD values between 2 and 11 were obtained. Chlorophyll a in
      several water matrices was determined with good results in presence of other
      pigments such as chlorophyll b, pheophytin a and pheophytin b.

PMID- 20678652
TI  - Screen-printed poly(3,4-ethylenedioxythiophene) (PEDOT): A new electrochemical
      mediator for acetylcholinesterase-based biosensors.
AB  - This work describes the use of a PEDOT:PSS-based conductive polymer for designing
      AChE-based biosensors. The transducers were obtained directly by screen-printing
      a PEDOT:PSS suspension on the surface of thick film carbon electrodes. The
      obtained working electrodes showed a high conductivity when compared with
      electrodes modified with conventional mediators like cobalt phthalocyanine or
      tetracyanoquinodimethane. The PEDOT:PSS polymer was shown to be suitable for
      thiocholine oxidation, allowing the measurement of AChE activity at 100 mV vs
      Ag/AgCl. The high conductivity of PEDOT:PSS allowed the accurate detection of the
      organophosphate insecticide chlorpyrifos-oxon at concentrations as low as 4x10(
      9)M, corresponding to an inhibition ratio of 5%.

PMID- 20678653
TI  - Simultaneous voltammetric determination of levodopa, carbidopa and benserazide in
      pharmaceuticals using multivariate calibration.
AB  - An analytical methodology based on differential pulse voltammetry (DPV) on a
      glassy carbon electrode and the partial least-squares (PLS-1) algorithm for the
      simultaneous determination of levodopa, carbidopa and benserazide in
      pharmaceutical formulations was developed and validated. Some sources of bi
      linearity deviation for electrochemical data are discussed and analyzed. The
      multivariate model was developed as a ternary calibration model and it was built
      and validated with an independent set of drug mixtures in presence of excipients,
      according with manufacturer specifications. The proposed method was applied to
      both the assay and the uniformity content of two commercial formulations
      containing mixtures of levodopa-carbidopa (10:1) and levodopa-benserazide (4:1).
      The results were satisfactory and statistically comparable to those obtained by
      applying the reference Pharmacopoeia method based on high performance liquid
      chromatography. In conclusion, the methodology proposed based on DPV data
      processed with the PLS-1 algorithm was able to quantify simultaneously levodopa,
      carbidopa and benserazide in its pharmaceuticals formulations using a ternary
      calibration model for these drugs in presence of excipients. Furthermore, the
      model appears to be successful even in the presence of slight potential shifts in
      the processed data, which have been taken into account by the flexible
      chemometric PLS-1 approach.

PMID- 20678654
TI  - Simultaneous quantification of amphetamines, caffeine and ketamine in urine by
      hollow fiber liquid phase microextraction combined with gas chromatography-flame
      ionization detector.
AB  - A method of hollow fiber (HF) liquid phase microextraction (LPME) combined with
      gas chromatography (GC)-flame ionization detection (FID) was developed for the
      simultaneous quantification of trace amphetamine (AP), methamphetamine (MA),
      methylenedioxyamphetamine (MDA), methylenedioxymethamphetamine (MDMA), caffeine
      and ketamine (KT) in drug abuser urine samples. The factors affecting on the
      extraction of six target analytes by HF-LPME were investigated and optimized, and
      the subsequent analytical performance evaluation and real sample analysis were
      performed by the extraction of six target analytes in sample solution containing
      30% NaCl (pH 12.5) for 20 min with extraction temperature of 30 degrees C and
      stirring rate of 1000 rpm. Under such optimal conditions, the limits of detection
      (LODs, S/N=3) for the six target analytes were ranged from 8 microg/L (AP, KT) to
      82 microg/L (MDA), with the enrichment factors (EFs) of 5-227 folds, and the
      relative standard deviations (RSDs, n=7) were in the range of 6.9-14.1%. The
      correlation coefficients of the calibration for the six target analytes over the
      dynamic linear range were higher than 0.9958. The application feasibility of HF
      LPME-GC-FID in illegal drug monitoring was demonstrated by analyzing drug abuser
      urine samples, and the recoveries of target drugs for the spiked sample ranging
      from 75.2% to 119.3% indicated an excellent anti-interference capability of the
      developed method. The proposed method is simple, effective, sensitive and low
      cost, and provides a much more accurate and sensitive detection platform over the
      conventional analytical techniques (such as immunological assay) for drug abuse
      analysis.

PMID- 20678655
TI  - A simple miniaturised photometrical method for rapid determination of nitrate and
      nitrite in freshwater.
AB  - A rapid, simple miniaturised photometrical method was developed for the
      determination of nitrate and/or nitrite in freshwater samples. All procedures,
      including sample buffering, reduction by copperised cadmium granules, colour
      development and absorbance determination, were completed in a 96-well microplate.
      The factors governing the nitrate reduction and its recovery were investigated in
      detail, and the optimised analysing conditions were established. Nitrate was
      quantitatively reduced by copperised cadmium granules with a high reduction
      efficiency (96.59+/-0.96%). The proposed method gave a linear calibration ranging
      from 0.01 to 1.50 mg L(-1) for NO(2)(-)-N and 0.02 to 1.50 mg L(-1) for NO(3)(-)
      N. The detection limits for nitrite and nitrate were 2 and 4 microg L(-1),
      respectively. The proposed method allowed at least 48 samples to be
      simultaneously analysed in duplicate, with good precision, within 90 min for
      nitrate and 30 min for nitrite, and was successfully applied to actual freshwater
      sample analysis with a recovery of 98.02+/-1.04% for nitrite and 99.72+/-1.39%
      for nitrate. This method produced accurate results comparable to standard
      methods, provided a much higher sample throughput than conventional methods and
      could be routinely used in actual freshwater sample monitoring.

PMID- 20678656
TI  - Extraction and preconcentration of beta-blockers in human urine for analysis with
      high performance liquid chromatography by means of carrier-mediated liquid phase
      microextraction.
AB  - A novel method was developed for the analysis of four beta-blockers, namely
      sotalol, carteolol, bisoprolol, and propranolol, in human urine by coupling
      carrier-mediated liquid phase microextraction (CM-LPME) to high performance
      liquid chromatography (HPLC). By adding an appropriate carrier in organic phase,
      simultaneous extraction and enrichment of hydrophilic (sotalol, carteolol, and
      bisoprolol) and hydrophobic (propranolol) drugs were achieved. High enrichment
      factors were obtained by optimizing the compositions of the organic phase, the
      acceptor solution, the donor solution, the stirring rate, and the extraction
      time. The linear ranges were from 0.05 to 10.0 mg L(-1) for sotalol and
      carteolol, and from 0.05 to 8.0 mg L(-1) for bisoprolol and propranolol. The
      limits of detection (S/N=3) were 0.01 mg L(-1) for sotalol, carteolol, and
      bisoprolol, and 0.005 mg L(-1) for propranolol. The relative standard deviations
      were lower than 6%. The developed method exhibited high analyte preconcentration
      and excellent sample clean-up effects with little solvent consumption and was
      found to be sensitive and suitable for simultaneous determination of the above
      four drugs spiked in human urine. Furthermore, the successful analysis of
      propranolol in real urine specimens revealed that the determination of beta
      blockers in human urine is feasible using the present method.

PMID- 20678657
TI  - Displacement-dispersive liquid-liquid microextraction coupled with graphite
      furnace atomic absorption spectrometry for the selective determination of trace
      silver in environmental and geological samples.
AB  - A novel displacement-dispersive liquid-liquid microextraction method was
      developed for the selective determination of trace silver in complicated samples
      by graphite furnace atomic absorption spectrometry. This method involves two
      steps of dispersive liquid-liquid microextraction (DLLME). Firstly, copper ion
      reacted with diethyldithiocarbamate (DDTC) to form Cu-DDTC complex and extracted
      with DLLME procedure using carbon tetrachloride (extraction solvent) and methanol
      (dispersive solvent); then, the sedimented phase was dispersed into the sample
      solution containing silver ion with methanol and another DLLME procedure was
      carried out. Because the stability of Ag-DDTC is larger than that of Cu-DDTC,
      Ag(+) can displace Cu(2+) from the pre-extracted Cu-DDTC and thus the
      preconcentration of Ag(+) was achieved. Potential interference from co-existing
      transition metal ions with lower DDTC complex stability was largely eliminated as
      they cannot displace Cu(2+) from Cu-DDTC complex. The tolerance limits for the co
      existing ions were increased by a long way compared with conventional DLLME.
      Under the optimal conditions, the limit of detection was 20 ng L(-1) (3sigma) for
      silver with a sample volume of 5.0 mL, and an enhancement factor of 72 was
      achieved. The proposed method was successfully applied to determine of trace
      silver in some environmental and geological samples with satisfactory results.

PMID- 20678658
TI  - H2O2-sensitive quantum dots for the label-free detection of glucose.
AB  - A novel label-free detection system based on CdTe/CdS quantum dots (QDs) was
      designed for the direct measurement of glucose. Herein we demonstrated that the
      photoluminescence (PL) of CdTe/CdS QDs was sensitive to hydrogen peroxide
      (H(2)O(2)). With d-glucose as a substrate, H(2)O(2) that intensively quenched the
      QDs PL can be produced via the catalysis of glucose oxidase (GOx). Experimental
      results showed that the decrease of the QDs PL was proportional to the
      concentration of glucose within the range of 1.8 microM to 1mM with the detection
      limit of 1.8 microM under the optimized experimental conditions. In addition, the
      QD-based label-free glucose sensing platform was adapted to 96-well plates for
      fluorescent assay, enhancing the capabilities and conveniences of this detection
      platform. An excellent response to the concentrations of glucose was found within
      the range of 2-30 mM. Glucose in blood and urine samples was effectively detected
      via this strategy. The comparison with commercialized glucose meter indicated
      that this proposed glucose assay system is not only simple, sensitive, but also
      reliable and suitable for practical application. The high sensitivity,
      versatility, portability, high-throughput and low cost of this glucose sensor
      implied its potential in point-of-care clinical diagnose of diabetes and other
      fields.

PMID- 20678659
TI  - Solid phase single-molecule counting of antibody binding to supported protein
      layers surface with low nonspecific adsorption.
AB  - On the basis of the supported protein layers (SPLs) substrate, the study
      presented an ultrasensitive and highly specific platform for single-molecule
      fluorescence detection of antibody using quantum dots (QDs) as probes. To
      construct the SPLs surface platform for antibody immobilization, bovine serum
      albumin (BSA), anti-BSA, and protein G were firstly attached to carboxyl
      terminated substrate surfaces by turns. Then nonspecific adsorption of single
      antibody molecules on SPLs surfaces was investigated. Through the irreversible
      interaction between streptavidin and biotin, streptavidin-QD conjugates were
      employed to conjugate with biotinylated antibody, producing QD-antibody
      conjugates for generating fluorescent signals in fluorescent imaging. Epi
      fluorescence microscopy equipped with an electron multiplying charge-coupled
      device was chosen as the tool for single-molecule fluorescence detection here.
      The concentration of antibody is quantified based on the direct counting of
      individual fluorescent spots, one by one. The generated fluorescent signals
      increased with the increasing concentration of immobilized antibody and were
      found to be proportional to antibody concentrations. The better brightness and
      photostability of QDs, and slower increase in the number of counted molecules
      make a large linear dynamic range of 1.0x10(-14) to 3.0x10(-12)mol L(-1) between
      the number of single molecules and antibody concentrations, which is comparable
      to the previously reported surface-based SMD analysis.

PMID- 20678660
TI  - Temperature-assisted ionic liquid dispersive liquid-liquid microextraction
      combined with high performance liquid chromatography for the determination of
      anthraquinones in Radix et Rhizoma Rhei samples.
AB  - In this article, a novel method termed as temperature-assisted ionic liquid
      dispersive liquid-liquid microextraction (TA IL-DLLME) combining high performance
      liquid chromatography with diode array detection (HPLC-DAD) was developed for the
      determination of anthraquinones in Radix et Rhizoma Rhei samples. The ionic
      liquid (1-hexyl-3-methylimidazolium hexafluorophosphate) was used to replace
      volatile organic solvent as an extraction solvent for the extraction of
      anthraquinones (aloe-emodin, rhein, emodin, chrysophanol and physcion) from Radix
      et Rhizoma Rhei. Several important parameters influencing the extraction
      efficiency of TA IL-DLLME such as the type and volume of extraction solvent and
      disperser solvent, sample pH, extraction time, extraction temperature,
      centrifugation time as well as salting-out effects were optimized. Under the
      optimal conditions, the spiked recovery for each analyte was in the range of 95.2
      108.5%. The precisions of the proposed method were varied from 1.1% to 4.4%
      (RSD). All the analytes exhibited good linearity with correlation coefficients
      (r(2)) ranging from 0.9986 to 0.9996. The limits of detection for all target
      analytes were ranged from 0.50 to 2.02 microg L(-1) (S/N=3). The experimental
      results indicated that the proposed method was successfully applied to the
      analysis of anthraquinones in Radix et Rhizoma Rhei.

PMID- 20678661
TI  - Quantitative determination by temperature dependent near-infrared spectra.
AB  - Near-infrared (NIR) spectra are sensitive to the variation of experimental
      conditions, such as temperature. In this work, the relationship between NIR
      absorption spectra and temperature was quantitatively analyzed and applied to the
      quantitative determination of the compositions in mixtures. It was found that,
      for the solvents such as water and ethanol, a quantitative spectra-temperature
      relationship (QSTR) model between NIR spectra and temperature can be established
      by using partial least squares (PLS) regression. Therefore, the temperature of a
      solution can be predicted by using the model and NIR spectrum. Furthermore, it
      was also found that the difference between the predicted results of different
      solutions is a quantitative reflection of concentration. The variation of
      intercept in the relationship of the predicted and measured temperature can be
      used to determine the concentration of the compositions. The mixtures of water,
      methanol, ethanol and ethylenediamine in a concentration range of 5-80% (v/v)
      were studied. The calibration curves are found to be reliable with the
      correlation coefficients (R) higher than 0.99. Both the QSTR and calibration
      model may extend the application of NIR spectroscopy and provide novel techniques
      for analytical chemistry.

PMID- 20678662
TI  - Micro-flame ionization detector with a novel structure for portable gas
      chromatograph.
AB  - A micro-flame ionization detector (micro-FID) for portable gas chromatograph (GC)
      based on conventional mechanical fabrication techniques was developed and
      evaluated. Structure was redesigned and dimensions were optimized for best
      performance. Air is introduced from upper part of the detector, flowing downwards
      into the burning chamber along a narrow round gap between the collection
      electrode and the inner wall of the detector body, forming a uniform flow field
      around the burning jet. The lowest detection limit of the mu-FID was 5x10(-13)g/s
      for n-decane, with a linear response range of five orders of magnitude. The
      consumption of gases is only 10 ml/min for hydrogen, and 120 ml/min for air, that
      is about 1/3 of the gases required for conventional FIDs. A comparative study
      between the micro-FID and commercial FID was also performed that proved the
      advantages of the micro-FID. The micro-FID is simple in structure, low heating
      power, and low consumption of gases that not only decrease the cost of running,
      but also increase the portability of GC for filed applications.

PMID- 20678663
TI  - Kinetics independent spectrometric analysis using non-linear calibration
      modelling and exploitation of concentration gradients generated by a flow-batch
      system for albumin and total protein determination in blood serum.
AB  - An automatic method for kinetics independent spectrometric analysis is proposed
      in this study. It uses a non-linear calibration model that explores concentration
      gradients generated by a flow-batch analyser (FBA) for the samples, dye, and the
      single standard solution. The procedure for obtaining the gradients of the dye
      and standard solution is performed once at the beginning of analysis. The same
      procedure is applied thereafter for each sample. For illustration, the proposed
      automatic methodology was applied to determine total protein and albumin in blood
      serum by using the Biuret and Bromocresol Green (BCG) methods. The measurements
      were made by using a laboratory-made photometer based on a red and green bicolour
      LED (Light-Emitting Diode) and a phototransistor, coupled to a "Z" form flow
      cell. The sample throughput was about 50 h(-1) for albumin and 60 h(-1) for total
      protein, consuming about 7 microL of sample, 2.6 mL of BCG and 1.2 mL of biuret
      reagents for each determination. Applying the paired t-test for results from the
      proposed analyser and the reference method, no statistic differences at 95%
      confidence level were found. The absolute standard deviation was usually smaller
      than 0.2 g dL(-1). The proposed method is valuable for the determination of total
      protein and albumin; and can also be used in other determinations where kinetic
      effects may or may not exist.

PMID- 20678664
TI  - A spectrophotometric assay for quantification of artemisinin.
AB  - A sensitive and rapid spectrophotometric method for determination of artemisinin
      concentration is described. The method is based on the measurement of a reaction
      product of the drug in strong alkali solution. The interaction produces a
      homogenous electronic transition band from 250 to 330 nm with maximum transition
      at around 291 nm. The absorption curve shows Gaussian distribution with identical
      half bandwidth, thus providing information for formation of a possible mono-type
      reaction product. The 291 nm absorption intensity increases with increasing
      concentration of artemisinin and obeys Beer's law in the range of 0.44-172 nmol
      (ml(-1)). The optimum reaction conditions and other analytical parameters were
      evaluated including its recovery from human plasma and erythrocyte samples.

PMID- 20678665
TI  - Single-walled carbon nanotubes coated fibers for solid-phase microextraction and
      gas chromatography-mass spectrometric determination of pesticides in Tea samples.
AB  - Using a single-walled carbon nanotubes (SWCNTs) as stationary phase of solid
      phase microextraction (SPME) fibers, a simple, low cost and environmentally
      friendly method for extraction of 13 pesticides in Tea samples has been developed
      following gas chromatography-mass spectrometric determination. Potential factors
      affecting the extraction efficiency were investigated and optimized, including
      extraction and desorption time, extraction temperature, stirring rate, solution
      pH and ionic strength. Under optimized conditions, the linearity of the developed
      method was in the range of 0.125-25 ng/mL with correlation coefficients greater
      than 0.9928 and the limits of detections (LODs) were 0.027-0.23 ng/mL (S/N=3).
      Meanwhile, the relative standard deviations (RSDs) for five successive
      measurements with single fiber, fiber-to-fiber, day-to-day were 2.3-13.0, 8.2
      14.6 and 4.1-12.5%, respectively, indicating good reproducibility of the proposed
      method. The fiber had high extraction efficiency for studied pesticides in
      comparison with commercial poly(dimethylsiloxane) (PDMS) and polyacrylate (PA)
      fibers and could be used for more than 70 times without decrease of efficiency.
      The developed method was successfully applied for the analysis of real samples
      including green Tea, oolong Tea, white Tea, and flower Tea, and the recoveries of
      the pesticides spiked in these samples ranged from 75.1 to 118.4%. Chlorfenapyr
      and lambda-cyhalothrin were found in the Tea samples bought randomly from local
      market. The results demonstrated that the developed SWCNTs-SPME method was a
      simple, efficient pretreatment and enrichment procedure for pesticides in complex
      matrices.

PMID- 20678666
TI  - Enhanced oxygen sensing properties of Pt(II) complex and dye entrapped core-shell
      silica nanoparticles embedded in sol-gel matrix.
AB  - This paper presents a highly sensitive oxygen sensor that comprises an optical
      fiber coated at one end with platinum(II) meso
      tetrakis(pentafluorophenyl)porphyrin (PtTFPP) and PtTFPP entrapped core-shell
      silica nanoparticles embedded in an n-octyltriethoxysilane (Octyl
      triEOS)/tetraethylorthosilane (TEOS) composite xerogel. The sensitivity of the
      optical oxygen sensor is quantified in terms of the ratio I(0)/I(100), where I(0)
      and I(100) represent the detected fluorescence intensities in pure nitrogen and
      pure oxygen environments, respectively. The experimental results show that the
      oxygen sensor has a sensitivity (I(0)/I(100)) of 166. The response time was 1.3s
      when switching from pure nitrogen to pure oxygen, and 18.6s when switching in the
      reverse direction. The experimental results show that compared to oxygen sensors
      based on PtTFPP, PtOEP, or Ru(dpp)(3)(2+) dyes, the proposed optical fiber oxygen
      sensor has the highest sensitivity. In addition to the increased surface area per
      unit mass of the sensing surface, the dye entrapped in the core of silica
      nanoparticles also increases the sensitivity because a substantial number of
      aerial oxygen molecules penetrate the porous silica shell. The dye entrapped core
      shell nanoparticles is more prone to oxygen quenching.

PMID- 20678667
TI  - Analytical approach to the metallomic of Nile tilapia (Oreochromis niloticus)
      liver tissue by SRXRF and FAAS after 2D-PAGE separation: Preliminary results.
AB  - An investigation was made into calcium, iron and zinc in protein spots in samples
      of Nile tilapia (Oreochromis niloticus) liver tissue obtained after protein
      separation by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and
      subsequent qualitative and quantitative evaluation by synchrotron radiation X-ray
      fluorescence (SRXRF) and Flame Atomic Absorption Spectrometry (FAAS). An analysis
      of the fluorescence spectra indicated the presence of calcium, iron and zinc in
      12, 6 and 8 liver protein spots, respectively. The metal ions found were
      distributed mainly in proteins with a molar mass of less than 40.00 kDa and more
      than 12.00 kDa, with pI in the range of 4.70-9.40. The only exception was a spot
      presenting protein with a molar mass of 10.10 kDa. In addition to calcium, iron
      and zinc, sulfur and phosphorus - which are non-metals that may be part of the
      protein structure, were also detected. After microwave-assisted acid
      mineralization of the proteins spots, a FAAS estimation of the concentration of
      calcium, iron and zinc ions bound to these proteins indicated a range of 1.08
      5.80 mg g(-1), 2.02-8.03 mg g(-1) and 1.60-8.55 mg g(-1), respectively.

PMID- 20678668
TI  - Temperature dependence of fluorescence for EuCl3 in LiCl-KCl eutectic melt.
AB  - The fluorescence of EuCl(3) in LiCl-KCl eutectic melt according to temperature
      changes was investigated, and the spontaneous partial reduction of Eu(3+) to
      Eu(2+) at high temperature was confirmed by the fluorescence results. The
      fluorescence decreases when the temperature increases, and this was examined in
      detail. The studies of fluorescence provided information regarding the chemical
      and physical behavior of europium ions in the molten salt according to the
      temperature changes. It is applicable for monitoring species and concentrations
      and estimating the approximate chemical structure of the ions in molten salts.

PMID- 20678669
TI  - Enzyme separation and isozyme heterogeneity analysis using non-denaturing two
      dimensional electrophoresis.
AB  - Carboxylesterase and sorbitol dehydrogenase are separated by non-denaturing two
      dimensional electrophoresis (2-DE) of isoelectric focusing separation using 5%
      carrier ampholyte (pH 6-8) and 1.25% carrier ampholyte (pH 3-10) and size
      separation. Furthermore, activities of sorbitol, malate and lactate
      dehydrogenases are sequentially examined when the enzymes are separated by 2-DE
      and are sequentially reacted to sorbitol, malic and lactic acid, respectively, in
      the presence of nicotinamide adenine dinucleotide, nitro blue tetrazolium and
      phenazine methosulphate. Several kinds of enzymes including lactate dehydrogenize
      isozymes can be simultaneously separated using 2-DE. Furthermore, the binding
      differences between lactate dehydrogenase isozymes and concanavalin A (con A) can
      be examined using a combination of 2-DE and non-denaturing stacking gel
      electrophoresis. The results of this study indicate that non-denaturing 2-DE can
      be applied to both enzyme separation and isozyme heterogeneity analysis.

PMID- 20678670
TI  - 3D nanostructured Ni(OH)2 microspheres as an efficient immobilization matrix of
      Ru(bpy)3(2+) for high-performance electrochemiluminescence sensor.
AB  - The electrochemistry and electrochemiluminescence (ECL) of novel three
      dimensional nanostructured Ru(bpy)(3)(2+)/Ni(OH)(2) microspheres were
      investigated for the first time. The negatively charged porous Ni(OH)(2)
      microspheres composed of Ni(OH)(2) nanowires were specifically designed to
      interact with Ru(bpy)(3)(2+). The large surface area and porous structure of
      Ni(OH)(2) microspheres enhance loading of Ru(bpy)(3)(2+) and mass transport of
      the model analyte, tripropylamine (TPA). Excellent ECL performance of the
      presented sensor was achieved including good stability and wide linear range from
      7.7x10(-10) to 3.8x10(-3)M with the detection limit of 2.6x10(-10)M to TPA.

PMID- 20678671
TI  - Automated liquid-solid extraction of pyrene from soil on centrifugal microfluidic
      devices.
AB  - Organic pollutants such as polycyclic aromatic hydrocarbons (PAHs) are present in
      the environment in increasing concentrations and so are of growing concern.
      Monitoring these species, particularly on-site, can be both difficult and
      expensive. This paper presents a novel miniaturised magnetically actuated liquid
      solid extraction unit integrated in tandem with a filtration unit and a detection
      unit on a single centrifugal microfluidic device. A demonstration analyte,
      pyrene, was rapidly extracted and quantified by UV-absorbance from multiple soil
      samples. The system showed excellent performance for a system designed for field
      use. Characterization of two types of passive valves was performed along with an
      extraction time efficiency study. The system provides a factor of 150 reduction
      in sample weights and extraction solvent volumes and provides statistically
      similar recoveries to the conventional method with a pyrene detection limit of 1
      ppm (0.03 microg absolute detection limit). The reduction in time and solvent and
      the potential for field use suggest that this device type may be valuable for
      environmental monitoring.

PMID- 20678672
TI  - Effects of antidepressants in patients with irritable bowel syndrome and comorbid
      depression.
AB  - BACKGROUND: Irritable bowel syndrome (IBS) is a functional gastrointestinal
      disorder that affects up to 15% of community dwelling individuals. Psychiatric
      comorbidities, particularly symptoms of major depressive disorder (MDD), occur in
      up to 90% of patients with IBS. OBJECTIVE: This article reviews the available
      literature on the use of antidepressants for both IBS and psychiatric depressive
      symptoms in patients with IBS. METHODS: MEDLINE and International Pharmaceutical
      Abstracts (both, 1980-May 2010) were searched for English-language publications
      that involved antidepressant treatment of MDD in patients with IBS. The search
      terms were depression, irritable, bowel, treatment, and functional. The reference
      lists of key articles were searched for additional pertinent articles. Randomized
      controlled trials published in the past 10 years were given priority. RESULTS: Of
      46 articles identified by the literature search, 11 were included in the review:
      4 studies of selective serotonin reuptake inhibitors (SSRIs), 4 of tricyclic
      antidepressants (TCAs), 1 comparing an SSRI and a TCA, 1 of the serotonin
      norepinephrine reuptake inhibitor duloxetine, and a case report involving the
      tetracyclic antidepressant mirtazapine. Most of the identified studies excluded
      patients with a diagnosis of depression and/or anxiety. No controlled studies
      were identified in which the primary outcome was objective assessment of MDD
      symptoms in patients with IBS. Two of the SSRI studies, one of citalopram and the
      other of paroxetine, reported approximately 50% improvement in IBS symptoms (both
      studies, P = 0.01); the study of paroxetine reported a 30% improvement in scores
      on the Beck Depression Inventory (P = 0.01). The 2 studies of fluoxetine found no
      statistically significant benefit on IBS symptoms. TCAs were reported to have
      benefits on IBS symptoms, predominantly diarrhea. Only one of the TCA studies
      examined and found a significant improvement in depressive symptoms with
      desipramine 150 mg/d (P = 0.025). Both the open-label study of duloxetine and the
      case report involving mirtazapine found improvements in IBS and psychiatric
      symptoms. CONCLUSIONS: The evidence for the benefit of antidepressant treatment
      in patients with IBS and comorbid depression was limited and contradictory. Some
      anti-depressants may help symptoms of IBS, although whether the same drugs and
      doses are associated with improvements in concomitant depressive symptoms remains
      to be elucidated.

PMID- 20678673
TI  - Effectiveness and tolerability of high-dose (23 mg/d) versus standard-dose (10
      mg/d) donepezil in moderate to severe Alzheimer's disease: A 24-week, randomized,
      double-blind study.
AB  - BACKGROUND: Currently approved Alzheimer's disease (AD) treatments have been
      reported to provide symptomatic benefit, without proven impact on clinical
      progression. We hypothesized that the loss of initial therapeutic benefit over
      time may be mitigated by higher doses of a cholinesterase inhibitor. OBJECTIVE:
      The aim of this study was to determine the effectiveness and tolerability of
      increasing donepezil from 10 to 23 mg/d in patients with moderate to severe AD.
      METHODS: This randomized, double-blind study was conducted at 219 sites in Asia,
      Europe, Australia, North America, South Africa, and South America from June 6,
      2007, to March 27, 2009. Patients aged 45 to 90 years with probable AD, Mini
      Mental State Examination score 0 to 20 (moderate to severe impairment), and who
      were receiving donepezil 10 mg once daily for > or =12 weeks before the start of
      the study were eligible. Patients (n = 1467) were randomly assigned to receive
      high-dose donepezil (23 mg once daily) or standard-dose donepezil (10 mg once
      daily) for 24 weeks. Coprimary effectiveness measures were changes in cognition
      and global functioning, as assessed using least squares mean changes from
      baseline (LSM [SE] A) scores (last observation carried forward) on the Severe
      Impairment Battery (SIB; cognition) and the Clinician's Interview-Based
      Impression of Change Plus Caregiver Input scale (CIBIC+; global function rating)
      overall change score (mean [SD]) at week 24. Treatment-emergent adverse events
      (TEAEs) were assessed using spontaneous patient/caregiver reporting and open
      ended questioning; clinical laboratory testing (hematology, biochemistry, and
      urinalysis panels analyzed by a central laboratory); 12-lead ECG; and physical
      and neurologic examinations, including vital sign measurements. RESULTS: The
      effectiveness analyses included 1371 patients (mean age, 73.8 years; 62.8%
      female; 73.5% white; weight range, 34.0-138.7 kg). A total of 296 of 981 patients
      (30.2%) withdrew from the donepezil 23-mg/d group; 87 of 486 patients (17.9%)
      withdrew from the donepezil 10-mg/d group. At study end (week 24), the LSM (SE)
      Delta in SIB score was significantly greater with donepezil 23 mg/d than with
      donepezil 10 mg/d (+2.6 [0.58] vs +0.4 [0.66], respectively; difference, 2.2; P <
      0.001). The between-treatment difference in CIBIC+ score was nonsignificant (4.23
      [1.07] vs 4.29 [1.07]). In post hoc analysis, LSM Delta in SIB score and CIBIC+
      treatment effect at end point were greater with donepezil 23 mg/d than 10 mg/d in
      patients with more advanced AD compared with less impaired patients (SIB, +1.6
      [0.78] vs -1.5 [0.88], respectively [P < 0.001]; CIBIC+, 4.31 [1.09] vs 4.42
      [1.10] [P = 0.028]). TEAEs were reported in 710 of 963 patients (73.7%) who
      received donepezil 23 mg/d and in 300 of 471 patients (63.7%) who received
      donepezil 10 mg/d. With donepezil 23 mg/d, mild, moderate, and severe TEAEs were
      reported in 297 (30.8%), 332 (34.5%), and 81 (8.4%) patients, respectively; with
      donepezil 10 mg/d, these proportions were 147 (31.2%), 119 (25.3%), and 34
      (7.2%). The 3 most common severe AEs reported with the 23-mg/d dose were nausea
      (9 patients [0.9%] vs 1 [0.2%] with the 10-mg/d dose), dizziness (7 [0.7%] vs 1
      [0.2%]), and vomiting (6 [0.6%] vs 0). The most commonly reported TEAEs
      considered probably related to treatment with the 23-mg/d dose were nausea (59
      patients [6.1%] vs 9 [1.9%] with the 10-mg/d dose), vomiting (48 [5.0%] vs 4
      [0.8%]), and diarrhea (31 [3.2%] vs 7 [1.5%]).Thirteen deaths were reported
      during the study or within 30 days of study discontinuation (23 mg/d, 8 patients
      [0.8%]; 10 mg/d, 5 patients [1.1%]); all were considered unrelated to the study
      medication. CONCLUSIONS: In this study in patients with moderate to severe AD,
      donepezil 23 mg/d was associated with greater benefits in cognition compared with
      donepezil 10 mg/d. The between-treatment difference in global functioning was not
      significant in the overall population. Patients with more advanced AD appeared to
      benefit from donepezil 23 mg/d on the assessment of global functioning, but this
      observation requires additional studies for confirmation. ClinicalTrials.gov
      identifier: NCT00478205.

PMID- 20678674
TI  - Triple therapy with olmesartan medoxomil, amlodipine besylate, and
      hydrochlorothiazide in adult patients with hypertension: The TRINITY multicenter,
      randomized, double-blind, 12-week, parallel-group study.
AB  - BACKGROUND: Patients with hypertension may require a combination of > or =2
      antihypertensive agents to achieve blood pressure (BP) control. OBJECTIVE: The
      aim of this study was to determine whether a triple combination of olmesartan
      medoxomil (OM), amlodipine besylate (AML), and hydrochlorothiazide (HCTZ) had a
      clinically significant benefit compared with dual combinations of the individual
      components in patients with moderate to severe hypertension. METHODS: This was a
      multicenter, randomized, doubleblind, parallel-group study in which triple
      combination treatment with OM 40 mg + AML 10 mg + HCTZ 25 mg was compared with
      dual combinations of the individual components-OM 40 mg/AML 10 mg in fixed-dose
      combination, OM 40 mg/HCTZ 25 mg in fixed-dose combination, and AML 10 mg + HCTZ
      25 mg-in patients aged > or =18 years who had a mean seated BP > or =140/100 mm
      Hg or > or =160/90 mm Hg. The study consisted of a 3-week washout period with no
      study medication and a 12-week double-blind treatment period. In the first 2
      weeks of the double-blind treatment period, all patients were randomized to
      receive dual combination treatment or placebo. All patients assigned to a dual
      combination treatment group continued the assigned treatment until week 4, and
      all patients assigned to placebo were switched at week 2 to receive 1 of the dual
      combination treatments until week 4. At week 4, patients either continued dual
      combination treatment or switched to triple combination treatment until week 12.
      The primary end point was the change in seated diastolic BP (SeDBP) from baseline
      to week 12; SeDBP reduction of > or =2 mm Hg was considered a clinically
      significant benefit. Secondary efficacy end points included the change in seated
      systolic BP (SeSBP) at week 12 and the percentages of patients achieving BP
      targets of <140/90 mm Hg, <120/80 mm Hg, SeSBP <140 mm Hg, and SeDBP <90 mm Hg at
      week 12. The tolerability of the treatments was also evaluated based on adverse
      events (AEs), clinical laboratory evaluations (chemistry, hematology, and
      urinalysis), physical examinations, and 12-lead ECGs. RESULTS: The 2492
      randomized patients (52.9% male, 66.8% white, 30.4% black) had a mean (SD) age of
      55.1 (10.9) years and a mean weight of 96.0 (22.9) kg. Diabetes was present in
      15.5% of the population, chronic cardiovascular disease in 9.1%, and chronic
      kidney disease in 4.1%. At baseline, the mean SeBP was 168.5/100.9 mm Hg. At week
      12, triple combination treatment was associated with significantly greater least
      squares mean reductions in SeBP compared with the dual combinations (SeDBP: -21.8
      vs -15.1 to -18.0 mm Hg, respectively [P < 0.001]; SeSBP: -37.1 vs -27.5 to -30.0
      mm Hg [P < 0.001]). A significantly higher proportion of patients receiving
      triple combination treatment reached BP targets compared with the dual
      combinations at week 12 (P < 0.001). The proportions of patients reaching the BP
      target of <140/90 mm Hg at week 12 was 69.9% in the triple combination treatment
      group and 52.9%, 53.4%, and 41.1% in the treatment groups receiving OM 40 mg/AML
      10 mg, OM 40 mg/HCTZ 25 mg, and AML 10 mg + HCTZ 25 mg, respectively (P < 0.001,
      triple combination vs each dual combination). The incidence of treatment-emergent
      AEs (TEAEs) was 58.4% for triple combination treatment and 51.7% to 58.9% for the
      dual combinations; most TEAEs were mild or moderate in severity. The most common
      TEAEs in the triple combination treatment group were dizziness (9.9%), peripheral
      edema (7.7%), and headache (6.4%). In total, 52 patients (2.3%) discontinued the
      study due to TEAEs-6 (1.0%) in the OM 40 mg/AML 10 mg group, 12 (2.1%) in the OM
      40 mg/HCTZ 25 mg group, 11 (2.0%) in the AML 10 mg + HCTZ 25 mg group, and 23
      (4.0%) in the OM 40 mg + AML 10 mg + HCTZ 25 mg group. Thirty-two patients (1.4%)
      4 (0.7%), 5 (0.9%), 5 (0.9%), and 18 (3.1%) in the respective treatment groups
      discontinued the study due to drug-related TEAEs. CONCLUSIONS: In these adult
      patients with moderate to severe hypertension, triple combination treatment with
      OM 40 mg + AML 10 mg + HCTZ 25 mg was associated with significant BP reductions
      compared with dual combinations of the individual components. All treatments were
      generally well tolerated. ClinicalTrials. gov identifier: NCT00649389.

PMID- 20678675
TI  - Effectiveness of barnidipine 10 or 20 mg plus losartan 50-mg combination versus
      losartan 100-mg monotherapy in patients with essential hypertension not
      controlled by losartan 50-mg monotherapy: A 12-week, multicenter, randomized,
      open-label, parallel-group study.
AB  - BACKGROUND: Increasing the dose or adding a second antihypertensive agent are 2
      possible therapeutic choices when blood pressure (BP) is poorly controlled with
      monotherapy. OBJECTIVE: This study investigated the effectiveness and
      tolerability of barnidipine 10 or 20 mg added to losartan 50 mg versus losartan
      100 mg alone in patients with mild to moderate essential hypertension whose BP
      was uncontrolled by losartan 50-mg monotherapy. METHODS: This was a 12-week,
      multicenter, randomized, open-label, parallel-group study. Eligible patients
      (aged 30-74 years) had uncontrolled hypertension, defined as office sitting
      diastolic BP (DBP) > or =90 mm Hg and/or systolic BP (SBP) > or =140 mm Hg, and
      mean daytime DBP > or =85 mm Hg and/or SBP > or =135 mm Hg. All were being
      treated with losartan 50 mg at enrollment. After a 1-week run-in period while
      taking losartan 50 mg, patients were randomly assigned to 6 weeks of treatment
      with open-label barnidipine 10 mg plus losartan 50 mg or losartan 100-mg
      monotherapy. At the end of this period, patients with uncontrolled BP had
      barnidipine doubled to 20 mg and continued for an additional 6 weeks, whereas
      patients not achieving control on treatment with losartan 100 mg were
      discontinued. Office BP was measured at each visit, whereas 24-hour ambulatory BP
      monitoring (ABPM) was performed at randomization and at the final visit (ie,
      after 12 weeks of treatment, or at 6 weeks for patients not controlled on
      losartan 100 mg). The intent-to-treat population included all randomized patients
      who received at least one dose of study treatment and had valid ABPM recordings
      at baseline and the final visit. The primary end point was the change in daytime
      DBP between baseline and 12 weeks of treatment, compared between the combination
      treatment and monotherapy. Adverse events (AEs) were evaluated during each study
      visit. RESULTS: A total of 93 patients were enrolled (age range, 30-75 years; 60%
      [56/93] men). After the 1-week run-in period, 68 patients were randomly assigned
      to 6 weeks of treatment with open-label barnidipine 10 mg plus losartan 50 mg (n
      = 34) or losartan 100-mg monotherapy (n = 34). A total of 53 patients were
      evaluable (barnidipine plus losartan, n = 28; losartan, n = 25). After 6 weeks of
      treatment, 18 patients in the combination treatment group (64.3%) had their dose
      of barnidipine doubled from 10 to 20 mg because BP was not normalized by
      treatment, whereas 8 patients in the losartan group (32.0%) were discontinued for
      the same reason. The between-treatment difference (losartan alone - combination
      treatment) for changes from baseline in daytime DBP was -1.7 mm Hg (95% CI, -5.8
      to 2.4 mm Hg; P = NS). A similar result was observed for daytime SBP (-3.2 mm Hg;
      95% CI, -8.1 to 1.7 mm Hg; P = NS). Likewise, no significant differences were
      found for nighttime values (mean [95% CI] DBP, 0.5 mm Hg [-3.7 to 4.7 mm Hg];
      SBP, 1.5 mm Hg [-4.1 to 7.1 mm Hg]) or 24-hour values (DBP, -0.9 mm Hg [-4.8 to
      2.9 mm Hg]; SBP, -1.6 mm Hg [-5.9 to 2.7 mm Hg]). Combination treatment was
      associated with a significantly higher rate of SBP responder patients (ie, <140
      mm Hg or a reduction of > or =20 mm Hg) compared with monotherapy (82.1% [23/28]
      vs 56.0% [14/25]; P = 0.044). Drug-related AEs were reported in 4 patients taking
      combination treatment (total of 7 AEs, including 2 cases of peripheral edema and
      1 each of tachycardia, atrial flutter, tinnitus, confusion, and polyuria) and in
      2 patients taking losartan alone (total of 2 AEs, both tachycardia). CONCLUSIONS:
      This open-label, parallel-group study found that there was no significant
      difference in the BP-lowering effect of barnidipine 10 or 20 mg in combination
      with losartan 50 mg compared with losartan 100-mg monotherapy in these patients
      with essential hypertension previously uncontrolled by losartan 50-mg
      monotherapy. However, the percentage of responders for SBP was significantly
      higher with the combination. Both treatments were generally well tolerated.
      European Union Drug Regulating Authorities Clinical Trials (EudraCT) no. 2006
      001469-41.

PMID- 20678676
TI  - Impact of the implementation of a sepsis protocol for the management of fluid
      refractory septic shock: A single-center, before-and-after study.
AB  - BACKGROUND: Evidence-based guidelines have been published for the acute
      management of severe sepsis and septic shock. Key goals of institution-driven
      protocols include timely fluid resuscitation and antibiotic selection, as well as
      source control. OBJECTIVE: This study assessed the impact of a sepsis protocol on
      the timeliness of antibiotic administration, the adequacy of fluid resuscitation,
      and 28-day mortality in patients with fluid-refractory septic shock. METHODS:
      This was a single-center, before-and-after study (18 months before July 2007 and
      18 months after) with prospective data collection evaluating the outcomes of a
      sepsis protocol in adult patients with fluid-refractory septic shock. All
      patients received a fluid challenge and antibiotics; those who did not were
      excluded from this analysis. Preprotocol findings led to the development of the
      sepsis protocol, which emphasized fluid resuscitation, timely administration of
      antibiotic therapy, and collection of specimens for culture at the onset of
      septic shock. In the pre- and postprotocol phases of the study, data were
      collected prospectively and analyzed for demographic characteristics; Acute
      Physiology and Chronic Health Evaluation (APACHE) II score; appropriateness of
      fluid resuscitation; antibiotic use; number of vasopressor, ventilator, and
      intensive care unit (ICU) days; and 28-day mortality. Outcomes were measured
      prospectively at any time during the patient's hospital admission. The primary
      end points were the time to administration of antimicrobial therapy and the
      appropriateness of fluid resuscitation before and after implementation of the
      sepsis protocol. RESULTS: A total of 118 patients were included in the analysis:
      64 and 54 in the pre- and postprotocol groups, respectively. Patients in the
      preprotocol group were primarily women (53% [34/64]) and had a mean (SD) age of
      61 (15.5) years and a mean APACHE II score of 28 (6.0). Patients in the
      postprotocol group were primarily men (54% [29/54]) and had a mean age of 52
      (18.0) years and a mean APACHE II score of 27 (6.4). Implementation of the sepsis
      protocol resulted in a greater percentage of patients receiving timely antibiotic
      therapy (ie, within 4.5 hours of refractory shock; 85% [46/54] vs 56% [36/64]; P
      = 0.001) and adequate fluid resuscitation (72% [39/54] vs 31% [20/64]; P < 0.001)
      compared with the preprotocol group. Post hoc analysis found significant
      decreases in the number of vasopressor days (mean [SD], 3.8 [2.7] to 1.4 [1.5]; P
      < 0.001), ventilator days (9.1 [12.2] to 2.7 [4.0]; P < 0.001), and ICU days
      (12.3 [12.6] to 4.9 [3.9]; P < 0.001) in the postprotocol group. In-hospital
      mortality was not significantly different between the groups (survival 46%
      [28/61] before vs 54% [33/61] after the protocol). Multivariate analysis for
      predictors of in-hospital mortality identified an interval between shock and
      empiric antibiotic administration of >4.5 hours (odds ratio [OR] = 5.54; 95% CI,
      1.91-16.07; P < 0.002), vasopressor duration in days (OR = 1.27; 95% CI, 1.01
      1.59; P = 0.037), APACHE II score (OR = 1.14; 95% CI, 1.05-1.24; P = 0.003), and
      type of infection (community vs nosocomial, OR = 0.18; 95% CI, 0.05-0.61; P =
      0.006) as significant predictors. The 28-day mortality decreased from 61% (39/64)
      to 33% (18/54) after implementation of the protocol (P = 0.004). CONCLUSION:
      Implementation of a sepsis protocol emphasizing early administration of
      antibiotic therapy and adequate fluid resuscitation was associated with improved
      clinical outcomes and lower 28-day mortality in patients with fluid-refractory
      septic shock at this institution.

PMID- 20678677
TI  - Incidence and possible risk factors for clinical upper gastrointestinal events in
      patients taking selective cyclooxygenase-2 inhibitors: A prospective,
      observational, cohort study in Taiwan.
AB  - BACKGROUND: Use of selective cyclooxygenase (COX)-2 inhibitors is associated with
      a better gastrointestinal (GI) safety profile than use of other NSAIDs. However,
      the risk factors for clinical upper GI events (symptomatic ulcers and ulcer
      complications) in COX-2 inhibitor users have been rarely evaluated in the past.
      OBJECTIVE: The aim of this study was to assess the annual incidence of and
      identify the risk factors for clinical upper GI events in chronic COX-2 inhibitor
      (celecoxib and etoricoxib) users. METHODS: A prospective, hospital-based,
      observational cohort study was conducted in patients taking COX-2 inhibitors
      (celecoxib or etoricoxib) without comorbidity. COX-2 inhibitor prescription was
      conducted according to the guidelines issued by the Taiwan National Health
      Insurance and was identified by the computerized prescribing system of the Taipei
      Veterans General Hospital, Taipei, Taiwan. Patients with cardiovascular disease,
      pulmonary, hepatic or renal insufficiency, or malignancy were excluded. Patients
      received regular follow-up once a month. Between visits, patients were asked to
      report to the outpatient clinic if they had persistent ulcer or GI symptoms
      (dyspepsia, vomiting, nausea, heartburn, or acid regurgitation) not relieved by
      antacids for 1 week, or to the emergency department if they had evidence of GI
      bleeding or ulcer complications (melena, hematemesis, hematochezia, or sudden
      onset of severe epigastric pain). Endoscopy was performed to document any
      gastroduodenal ulcers with or without ulcer complications. The primary end point
      was the annual incidence and the significant risk factors for clinical upper GI
      events (symptomatic ulcers and ulcer complications). RESULTS: A total of 1158 COX
      2 inhibitor users were identified; 96 refused to participate and 129 were
      excluded. The mean (SD) age of the remaining 933 COX-2 inhibitor users was 69
      (15) years with 528 women (56.6%) and 405 men (43.4%). Mean time of follow-up was
      12.4 months. The annual incidence of clinical upper GI events in these patients
      taking COX-2 inhibitors was 4.6% (44 events/959 patient-years), with symptomatic
      ulcers in 3.6% and ulcer complications in 1.0%. Multivariate logistic regression
      analysis found that a history of peptic ulcer disease (PUD) (odds ratio [OR =
      4.61; 95% CI, 1.86-11.40; P = 0.001), concomitant use of steroids (OR = 2.99; 95%
      CI, 1.39-6.46; P = 0.005), aspirin (OR = 13.47; 95% CI, 5.89-30.82; P < 0.001),
      and other NSAIDs (OR = 60.49; 95% CI, 11.93-306.64; P < 0.001) were significant
      independent risk factors for clinical upper GI events in these patients taking
      COX-2 inhibitors. Age >60 years was not found to be a risk factor. CONCLUSIONS:
      The annual incidence of clinical upper GI events was 4.6% in these Taiwanese
      patients without comorbidity taking COX-2 inhibitors. A history of PUD and
      concomitant use of steroids, aspirin, or other NSAIDs, were found to be
      significant risk factors for clinical upper GI events in these patients.

PMID- 20678678
TI  - The need for oral antidiabetic treatment adherence studies in the pediatric
      population.

PMID- 20678679
TI  - A retrospective cohort study of economic outcomes and adherence to monotherapy
      with metformin, pioglitazone, or a sulfonylurea among patients with type 2
      diabetes mellitus in the United States from 2003 to 2005.
AB  - OBJECTIVES: The aims of this study were to compare all-cause total health care
      costs and diabetes mellitus (DM)-specific health care costs between patients who
      were adherent or nonadherent to monotherapy with metformin, pioglitazone, or a
      sulfonylurea and to examine whether cost differences varied among patients using
      these oral antidiabetic drugs. METHODS: This was a retrospective cohort study
      using data from the MEDSTAT MarketScan Research Databases. Patients aged 18 to 90
      years who were continuously insured between 2003 and 2005 and had > or =2
      outpatient claims or > or =1 inpatient claim with a diagnosis of DM
      (International Classification of Diseases, Ninth Revision, Clinical Modification
      code 250.xx) in 2003 were eligible for the study. To be part of the final sample,
      patients had to fill > or =2 prescriptions for metformin, pioglitazone, or a
      sulfonylurea during 2003, including > or =1 prescription during the last 3 months
      of the year. Patients were not eligible if they were taking polytherapy or a
      combination drug. All eligible patients were followed in 2004 and 2005. Adherence
      was calculated for each year using a medication possession ratio, and was
      dichotomized at > or =80% as either adherent or nonadherent. Annual all-cause
      health care costs and diabetes-specific costs were estimated using generalized
      linear models, adjusting for demographic characteristics, insurance, and comorbid
      conditions. RESULTS: A total of 108,592 patients who met the inclusion criteria
      were identified. Their mean age was 63 years; 49.8% (54,037/108,592) were women.
      More pioglitazone users resided in the north-central or south regions (81.3%
      [9364/11,520]) compared with metformin (62.4% [32,550/52,156]) or sulfonylurea
      (62.6% [28,105/44,916]) users (P < 0.001). Mean comorbidity scores were higher in
      the sulfonylurea (1.78) and pioglitazone (1.69) group than in the metformin group
      (1.45) (P < 0.001). Mean adherence ranged from 61.3% to 73.8% during the 2 years
      of follow-up. After adjustment, all-cause health care costs were $12,412 annually
      among adherent patients and $13,258 among nonadherent patients (difference, $846
      [95% CI, $747 to $945]). Diabetes-related health care costs were $2230 annually
      among adherent patients and $2284 among nonadherent patients (difference, $55
      [95% CI, $33 to $77]). In specific monotherapy groups, adjusted annual all-cause
      health care costs were $336 higher (95% CI, $216 to $456) for nonadherent
      metformin users, $1140 higher (95% CI, $793 to $1486) for nonadherent
      pioglitazone users, and $1509 higher (95% CI, $1339 to $1679) for nonadherent
      sulfonylurea users compared with adherent users. Compared with metformin users,
      sulfonylurea and pioglitazone users had greater adherence-related differences in
      all-cause health care costs (P < 0.05). There was no significant difference in
      diabetes-specific total costs between nonadherent and adherent patients taking
      metformin (difference, $6; 95% CI, -$31 to $20). Patients who were nonadherent to
      sulfonylureas had $271 higher (95% CI, $235 to $307) diabetes-specific costs per
      year than patients who were adherent to sulfonylureas. Patients who were
      nonadherent to pioglitazone had $433 lower (95% CI, -$516 to -$350) diabetes
      specific costs per year than patients who were adherent to pioglitazone.
      CONCLUSIONS: Adherence with metformin, pioglitazone, or a sulfonylurea was
      associated with overall cost reductions in the patients studied, but these cost
      reductions varied by monotherapy. Adherence to sulfonylureas or pioglitazone was
      associated with greater total cost reductions than was adherence to metformin.
      Health systems that commit resources to improving interventions may be able to
      achieve a return on investment if adherence to oral antidiabetic agents can be
      improved.

PMID- 20678680
TI  - Relative effectiveness of budesonide/formoterol and fluticasone
      propionate/salmeterol in a 1-year, population-based, matched cohort study of
      patients with chronic obstructive pulmonary disease (COPD): Effect on COPD
      related exacerbations, emergency department visits and hospitalizations,
      medication utilization, and treatment adherence.
AB  - BACKGROUND: According to evidence-based guidelines, the combination of inhaled
      corticosteroids and inhaled long-acting beta(2)-agonists in a single inhaler is
      recommended for patients with chronic obstructive pulmonary disease (COPD) who
      are experiencing exacerbations. The relative effectiveness of combination
      products such as budesonide/formoterol (BUD/FM) and fluticasone
      propionate/salmeterol (FP/SM) has not been well documented. OBJECTIVE: This study
      was conducted to investigate the different outcomes associated with the use of
      either BUD/FM or FP/SM in a single inhaler in patients with COPD. Outcomes
      included rates of exacerbations, emergency department (ED) visits and
      hospitalizations for COPD, medication utilization, and treatment adherence.
      METHODS: A 1-year, population-based, matched cohort study was conducted using
      administrative health care databases from the Canadian province of Quebec.
      Patients treated with BUD/FM were matched (1:1) to patients treated with FP/SM
      based on the following criteria: age group, sex, calendar year of treatment
      initiation, the number of COPD exacerbations in the year before treatment
      initiation, and use of inhaled short acting beta(2)-agonists (SABAs) and
      ipratropium bromide in the 3 months before treatment initiation. COPD
      exacerbations were defined as a claim for a short-course (< or =14 days)
      prescription of oral corticosteroids, or an ED visit or a hospitalization for
      COPD. Events occurring within 15 days were counted as a single exacerbation.
      Between-group comparisons of the number of exacerbations, ED visits, and
      hospitalizations for COPD, as well as claims for oral corticosteroids, were
      performed using Poisson regression models. Between-group comparisons of the mean
      number of doses of SABAs and ipratropium bromide per day were performed using
      linear regression models. Treatment adherence was also assessed. RESULTS: Of the
      2262 patients in the matched cohort, 78.1% were aged > or =65 years and 52.1%
      were men. COPD exacerbations, claims for oral corticosteroids, use of SABAs, and
      patient adherence to treatment did not differ significantly between the BUD/FM
      and FP/SM groups. However, the BUD/FM group was significantly less likely to have
      an ED visit (adjusted relative risk [RR] = 0.75; 95% CI, 0.58 to 0.97) or
      hospitalization (adjusted RR = 0.61; 95% CI, 0.47 to 0.81) for COPD and had fewer
      claims for prescriptions for tiotropium (adjusted RR = 0.71; 95% CI, 0.57 to
      0.89). The BUD/FM group also used fewer doses of ipratroprium bromide than the
      FP/SM group (adjusted mean difference, -0.2 dose; 95% CI, -0.3 to -0.1).
      CONCLUSIONS: These COPD patients treated with BUD/FM were less likely to have ED
      visits and hospitalizations for COPD and used fewer doses of anticholinergic
      medication than patients treated with FP/SM in the year after treatment
      initiation. However, due to the observational nature of the study design, we
      cannot conclude with certainty that the medication was the only factor
      responsible for the observed differences.

PMID- 20678681
TI  - Relationship between rheumatoid arthritis disease severity, health-related
      utility, and resource use in Australian patients: A cross-sectional, multicenter
      study.
AB  - OBJECTIVES: This research explores the relationship between rheumatoid arthritis
      (RA) severity measures, clinical characteristics, and patient preference-based
      health-related quality of life (ie, utility) in Australian RA patients. A
      secondary objective was to investigate the relationship between a range of
      disease severity measures, clinical characteristics, and the cost of RA-related
      resource use. METHODS: This was a cross-sectional, multicenter study of
      consecutive patients with RA aged > or =18 years attending routine clinical
      appointments. Patients completed a questionnaire comprising general demographic,
      resource use, and disease-specific questions; the RA-specific Health Assessment
      Questionnaire (HAQ); and 2 multiattribute preference-based quality-of-life
      (utility) instruments, the Health Utilities Index Mark 3 (HUI3) and the EuroQol 5
      Dimensions (EQ-5D). A second questionnaire was completed by the patient's
      rheumatologist, with questions on key clinical data pertinent to RA, including
      the number and location of tender joints and swollen joints, erythrocyte
      sedimentation rate (ESR), C-reactive protein (CRP) concentration, current and
      previous treatments, and details of important comorbid conditions. Data on RA
      specific resource use were also collected, including health-professional visits
      (eg, general practitioner, specialist, nurse, occupational therapist, paid
      caregivers), hospital admissions, surgery, and RA-associated home modifications.
      Spearman nonparametric correlation, simple linear, multiple, and stepwise
      regression analyses were used to explore the relationship between utility scores
      (HUI3 and EQ-5D) and variables including HAQ, RA-related resource use, and key
      demographic, physical, and biochemical measures. RESULTS: A total of 170 patients
      were recruited from 4 centers in Australia. Consistent with the epidemiology of
      RA, the ratio of women to men was approximately 3:1 (126 vs 44, respectively).
      Male and female patients were of similar age (mean [SD], 59.2 [12.9] and 58.9
      [12.2] years, respectively). Time since diagnosis of RA was significantly shorter
      for men than for women (mean difference, -4.52 years; 95% CI, -8.65 to -0.38; P =
      0.03). Of all the disease severity measures and clinical characteristics
      investigated, patients' HAQ scores predicted their utility most closely (for
      HUI3, R(2) = 0.626, P < 0.001; for EQ-5D, R(2) = 0.403, P < 0.001). The Disease
      Activity Score 28 severity index provided the next best relationship with a
      patient's utility; however, its explanatory power was poor (for HUI3, R(2) =
      0.085, P < 0.001; for EQ-5D, R(2) = 0.042, P = 0.008). ESR, CRP, and, RA-affected
      joint counts had negligible explanatory power for patient utility. In analyses of
      the relationship between a range of key variables and the direct costs associated
      with RA, the HAQ score explained 22% of the variability in log costs (P < 0.001).
      CONCLUSION: This study found that of all the disease severity measures and
      clinical characteristics investigated, patients' HAQ scores predicted their
      utility most closely.

PMID- 20678682
TI  - Cost-effectiveness of ranibizumab for the treatment of neovascular age-related
      macular degeneration in Germany: Model analysis from the perspective of Germany's
      statutory health insurance system.
AB  - BACKGROUND: In clinical trials, ranibizumab has been associated with
      stabilization and even improvement of visual acuity among patients with
      neovascular age related macular degeneration (AMD), but its use is also
      associated with considerable costs. OBJECTIVE: The aim of this work was to
      compare ranibizumab with best supportive care or photodynamic therapy (PDT) for
      AMD by means of economic cost-utility and cost-effectiveness analysis from the
      perspective of Germany's Statutory Health Insurance System. METHODS: Visual
      acuity data from the Anti-VEGF (vascular endothelial growth factor) Antibody for
      the Treatment of Predominantly Classic Choroidal Neovascularization in AMD
      (ANCHOR) and Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab
      in the Treatment of Neovascular AMD (MARINA) studies were applied, based on a
      ranibizumab dose of 0.5 mg. A Markov model simulated visual acuity and costs over
      10 years (discounted at 3%). The base-case analysis assumed 5 injections per year
      over 2 years. Treatment costs were based on year-2008 euros (using German prices)
      and recommendations for procedure reimbursement from a public health insurance
      perspective. To assess cost-effectiveness, costs per year of legal blindness
      avoided (ie, vision-year gained [VYG]) and per quality-adjusted life-year (QALY)
      were calculated. The model assumed each patient's affected eye had better sight
      than the other eye, and the 2 comparators against which ranibizumab treatment was
      assessed were best supportive care and PDT. The robustness of the results was
      investigated in a univariate sensitivity analysis of all relevant parameters and
      a multivariate probabilistic sensitivity analysis. The multivariate 95% CIs for
      incremental cost-effectiveness ratios were obtained by conducting 1000 Monte
      Carlo simulations. RESULTS: Compared with best supportive care, costs per VYG for
      ranibizumab were euro6767 in occult choroidal neovascularization (CNV) and
      euro6020 in minimally classic CNV. In classic CNV, costs were euro5734/VYG for
      ranibizumab compared with supportive care and euro778/VYG for ranibizumab
      compared with PDT. Costs per QALY for ranibizumab treatment for occult, minimally
      classic CNV, and classic CNV were euro22,320, euro22,538, and euro25,036,
      respectively, and euro3294 for classic CNV compared with PDT. Results were
      sensitive to the cost of blindness, injection frequency, and duration. The
      multivariate 95% CIs for the incremental cost effectiveness ratios were
      euro14,438 to euro41,110/QALY for occult CNV, euro13,463 to euro43,614/QALY for
      minimally classic CNV, and euro15,634 to euro51,106/QALY for classic CNV.
      CONCLUSION: In this model analysis using costs and clinical trial data from
      Germany, ranibizumab appeared to be a cost-effective treatment option for all
      angiographic subtypes of neovascular AMD, from the perspective of Germany's
      Statutory Health Insurance System.

PMID- 20678683
TI  - Pregabalin and gabapentin in matched patients with peripheral neuropathic pain in
      routine medical practice in a primary care setting: Findings from a cost
      consequences analysis in a nested case-control study.
AB  - BACKGROUND: Pregabalin and gabapentin are marketed to treat peripheral
      neuropathic pain, but head-to-head comparison is lacking. OBJECTIVES: The aims of
      this work were to compare the effects of pregabalin and gabapentin on different
      patient-reported health outcomes and to analyze health care and nonhealth-care
      resource consumption and their related costs among patients treated for
      peripheral neuropathic pain in primary medical care. METHODS: A cost-consequences
      comparison in subjects with refractory (suboptimal response to > or =1 previous
      analgesic treatment for >6 months) chronic peripheral neuropathic pain was
      carried out using data extracted from two 12-week, observational, prospective
      studies in primary medical care. Patients were eligible if they were aged > or
      =18 years, had a score of > or =4 on the Douleur Neuropathique 4 questionnaire,
      and were able to complete health questionnaires written in Spanish. A nested
      paired case-control design was chosen to perform the comparison with 2 controls
      (pregabalin) per case (gabapentin) matched by age, sex, peripheral neuropathic
      pain condition, time since diagnosis, number of previous treatments, pain
      intensity, depressive and anxiety symptom scores, and health state. Adult
      subjects with refractory chronic pain because of diabetic neuropathy,
      postherpetic or trigeminal neuralgias, or cervical or lumbosacral radiculopathies
      were included. Epidemiologic statistical methods were applied for comparing
      health effects (pain intensity, sleep, anxiety and depressive symptoms,
      disability, and health state), resources utilization, and related cost variations
      after 12 weeks. Indirect costs were measured by means of lost-workday equivalent
      calculations multiplied by the mean national daily salary. RESULTS: Analysis
      included 44 patients treated with gabapentin (cases) and 88 patients treated with
      pregabalin (controls) who were matched for age, sex, and other parameters. The
      mean (SD) gabapentin and pregabalin doses were 1263 (540) and 202 (119) mg/d,
      respectively. Although there was a greater reduction in last-week mean pain
      intensity with pregabalin (visual analog scale: 39.1 [22.5] vs 28.0 [22.2] mm; P
      = 0.008), as well as more patients with a > or =50% reduction in pain rate (60.9%
      vs 40.5%; P = 0.029), there were no significant differences between groups for
      sensory, affective, total, or present pain intensity. The significantly higher
      drug cost associated with pregabalin was offset by a greater reduction in
      productivity costs compared with gabapentin, yielding similar cost reduction (
      euro1254 [1479] vs -euro1384 [2874], respectively; P = NS). CONCLUSION:
      Pregabalin appeared to be associated with greater reduction in mean weekly
      intensity of pain, but there were no significant differences in cost.

PMID- 20678684
TI  - An open-label, randomized, single-center, two-period, phase I, crossover study of
      the effect of zibotentan (ZD4054) on the pharmacokinetics of midazolam in healthy
      male volunteers.
AB  - BACKGROUND: Zibotentan (ZD4054) is an oral, specific endothelin A receptor
      antagonist presently under investigation for the treatment of hormone-resistant
      prostate cancer. Preclinical in vitro studies suggest that zibotentan has the
      potential to act as a time-dependent inhibitor of the cytochrome P450 isozyme 3A4
      (CYP3A4) metabolic pathway. In clinical practice, it is likely that zibotentan
      will be coadministered with drugs metabolized by this pathway; the potential
      exists, therefore, that zibotentan-induced drug interactions could occur.
      OBJECTIVES: The primary objective of this study was to evaluate the effect of
      zibotentan on the pharmaco-kinetics of a clinically relevant dose of midazolam in
      healthy volunteers. Secondary objectives were to evaluate exposure to zibotentan,
      ensure the safety of the healthy volunteers dosed, and investigate the effect of
      zibotentan on the pharmacokinetics of the midazolam metabolites 1-hydroxy
      midazolam and 4-hydroxy midazolam. The potency of zibotentan as a CYP3A4
      inhibitor was also assessed. METHODS: This was an open-label, randomized,
      singlecenter, 2-period, Phase I, crossover study. Volunteers were randomized in a
      1:1 ratio to 1 of 2 cohorts. In cohort 1, volunteers received a single dose of
      midazolam 7.5 mg on day 1 (treatment A) of a 2-day study period. After a minimum
      7-day washout period, volunteers received zibotentan 10 mg once daily on days 1
      through 7, plus a single dose of midazolam 7.5 mg on day 6 (treatment B) of a 7
      day study period. In cohort 2, volunteers received treatment B followed by
      treatment A, with a minimum 7-day washout period between treatments. AUC(0
      infinity) and C(max) data were expressed as geometric least squares mean ratios
      and 90% CIs for midazolam + zibotentan:midazolam. A moderate interaction between
      midazolam and zibotentan was predefined to have occurred if the upper 90% CI of
      the ratio was >1.5. Adverse events (AEs) were assessed according to the National
      Cancer Institute's Common Terminology Criteria for Adverse Events version 3. AE
      data were assessed based on information provided by the volunteer, through open
      ended and nonleading verbal questions to the volunteer at each visit, and through
      observation by the investigational team, other care providers, or relatives.
      RESULTS: Six volunteers (all white) were included in each cohort (cohort 1, mean
      [SD] age, 48 [7] years; mean weight, 74 [6] kg; cohort 2, mean age, 51 [11]
      years; mean weight, 75 [13] kg). Steady-state levels of zibotentan, achieved over
      7 days, increased the midazolam AUC(0-infinity) by 1.2-fold compared with
      midazolam alone. The upper limits of the 90% CIs for the AUC(0-infinity) and
      C(max) ratios were below the predefined level of 1.5 (1.37 and 1.32,
      respectively). Zibotentan had no apparent effect on the pharmacokinetics of 1
      hydroxy midazolam and 4-hydroxy midazolam. Fatigue was reported in 11 volunteers
      (92%) receiving midazolam monotherapy and 10 (83%) receiving midazolam combined
      with zibotentan. Headache was reported in all 12 volunteers after zibotentan
      monotherapy. CONCLUSIONS: In this population of healthy male volunteers, once
      daily zibotentan 10 mg increased the AUC(0-infinity) of midazolam 1.2-fold;
      however, the treatment ratio was below the predefined limit for clinical
      significance. Zibotentan was well tolerated when given alone or in combination
      with midazolam. The results indicate that once-daily zibotentan 10 mg acted as a
      weak inhibitor of the CYP3A4 pathway. ClinicalTrials. gov identifier:
      NCT00709553.

PMID- 20678685
TI  - Pharmacokinetics and bioequivalence evaluation of two losartan potassium 50-mg
      tablets: A single-dose, randomized-sequence, open-label, two-way crossover study
      in healthy Chinese male volunteers.
AB  - BACKGROUND: Losartan is a nonpeptide angiotensin II receptor antagonist used as
      an antihypertensive agent. The relative bioavailability of a newly developed
      tablet compared with an established branded formulation has not been reported in
      a Chinese population. OBJECTIVE: To meet the requirements for marketing a new
      generic product, the study was designed to compare the pharmacokinetic parameters
      and relative bioavailability of a new generic losartan potassium 50-mg tablet
      (test formulation) with a branded 50-mg tablet (reference formulation) in healthy
      Chinese male volunteers. METHODS: A single-dose, randomized-sequence, openlabel,
      2-way crossover study was conducted in healthy Chinese male volunteers. Eligible
      participants were randomly assigned in a 1:1 ratio to receive a single 50-mg
      tablet of the test or reference formulation, followed by a 1-week washout period
      and then administration of the alternate formulation. The study drugs were
      administered after a 10-hour overnight fast. Plasma samples were collected over
      36 hours. Tolerability was evaluated by recording adverse events (AEs) and
      monitoring vital signs, ECGs, and laboratory tests at baseline and at completion
      of the study. Plasma concentrations of losartan and its active metabolite
      (EXP3174) were analyzed by LC-MS/MS. Pharmacokinetic parameters, including
      C(max), AUC(0-36), and AUC(0-infinity), were calculated. If the 90% CIs for the
      log-transformed values of AUC were within 80% to 125%, and that of C(max) was
      within 70% to 143%, the 2 products would be considered bioequivalent according to
      the guidelines of the US Food and Drug Administration and the State Food and Drug
      Administration of China. RESULTS: Twenty-seven healthy Chinese male volunteers
      participated in this study (mean [SD] age, 24.5 [2.3] years [range, 20-29 years];
      weight, 64.6 [4.0] kg [range, 60.0-75.0 kg]; height, 172.2 [4.8] cm [range,
      165.0183.0 cm]; and body mass index, 21.8 [1.2] kg/m(2) [range, 20.0-25.0
      kg/m(2)]). One volunteer (3.7%) experienced an AE (microscopic hematuria) after
      administration of the test formulation. This resolved spontaneously after 10 days
      and was considered by the investigator as mild; the relationship with the study
      drug was uncertain. No serious AEs were reported. Both formulations were
      associated with significant reductions in systolic and diastolic blood pressure
      and significant increases in heart rate compared with baseline values (all, P <
      0.05). No period, formulation, or sequence effects were observed for any
      pharmacokinetic parameter, except for a significant subject effect. For parent
      losartan, the 90% CIs for the ratios (test/reference) of C(max), AUC(0-36), and
      AUCAUC(0-infinity) were 83.65% to 113.36%, 89.79% to 98.25%, and 90.95% to
      99.55%, respectively. For the metabolite EXP3174, the 90% CIs for the ratios of
      C(max), AUC(0-36), and AUCAUC(0-infinity) were 93.49% to 103.61%, 96.79% to
      104.09%, and 97.06% to 105.83%. Both C(max) and AUC met the predetermined
      criteria for assuming bioequivalence. The relative bioavailability of the test
      formulation to the reference formulation was 93.92% for losartan and 100.40% for
      EXP3174. CONCLUSIONS: In this small study in healthy Chinese male volunteers, a
      single 50-mg oral dose of a losartan potassium tablet (test formulation) met the
      regulatory criteria for assuming bioequivalence to the established reference
      formulation. Both formulations were well tolerated.

PMID- 20678686
TI  - Pharmacokinetics and bioequivalence evaluation of two different atorvastatin
      calcium 10-mg tablets: A single-dose, randomized-sequence, open-label, two-period
      crossover study in healthy fasted Chinese adult males.
AB  - BACKGROUND: Atorvastatin calcium is a 3-hydroxy-3-methylglutaryl-coenzyme A
      reductase inhibitor indicated for the prevention of cardiovascular disease and
      for the treatment of dyslipidemia. Information on the pharmacokinetics of
      atorvastatin in a Chinese population is lacking, and regulatory requirements
      necessitate a bioequivalence study for the marketing of a generic product in
      China. OBJECTIVE: The aim of the present study was to assess the pharmacokinetics
      and bioequivalence of a test and branded reference formulation of atorvastatin
      calcium 10-mg tablets in healthy fasted Chinese male volunteers. METHODS: This
      was a single-dose, randomized-sequence, open-label, 2-period crossover study with
      a 2-week washout period between doses. Healthy Chinese males were randomly
      assigned to receive 20 mg of either the test or reference formulation, and 13
      blood samples were obtained over a 48-hour interval. Plasma concentrations of
      parent atorvastatin and ortho-hydroxy-atorvastatin (primary active metabolite)
      were simultaneously determined using a validated liquid chromatography-isotopic
      dilution mass spectrometry method. Pharmacokinetic parameters, including C(max),
      T(max), t((1/2)), AUC(0-t), and AUC(0-infinity)), were calculated. The 2
      formulations were to be considered bioequivalent if 90% CIs for the log
      transformed ratios of AUC and C(max) of atorvastatin were within the
      predetermined bioequivalence range (0.80-1.25 for AUC and 0.70-1.43 for C(max))
      as established by the State Food and Drug Administration of China. Tolerability
      was evaluated throughout the study by vital signs monitoring, physical
      examinations, 12-lead ECGs, and subject interviews on adverse events (AEs).
      RESULTS: A total of 66 subjects were assessed for inclusion; 20 were excluded
      prior to study initiation. Of the 46 healthy subjects (mean [SD] age, 24.1 [2.5]
      years; height, 170.8 [5.1] cm; weight, 64.6 [6.4] kg; body mass index (BMI), 22.1
      [1.7] kg/m(2)) who completed the study, 45 subjects (mean [SD] age, 24.1 [2.5]
      years; height, 171.1 [4.9] cm; weight, 64.8 [6.3] kg; BMI, 22.1 [1.7] kg/m(2))
      were included in the pharmacokinetic and bioequivalence analyses; 1 subject was
      excluded from these analyses because he mistakenly received the same formulation
      in both periods. No period or sequence effect was observed. The mean values of
      C(max), AUC(0-t), and AUC(0-infinity)) for the test and reference formulations of
      atorvastatin (8.78 and 10.76 ng/mL, 38.22 and 40.02 ng/mL/h, 42.73 and 44.51
      ng/mL/h, respectively) and ortho-hydroxy-atorvastatin (5.78 and 5.77 ng/mL, 47.32
      and 48.47 ng/mL/h, 52.36 and 53.14 ng/mL/h) were not significantly different. The
      90% CIs for natural log-transformed ratios of C(max), AUC(0-t), and AUC(0
      infinity)) of both atorvastatin (0.73-0.91, 0.92-1.02, and 0.91-1.01,
      respectively) and ortho-hydroxy-atorvastatin (0.83-1.05, 0.92-1.02, and 0.93
      1.02) were within the bioequivalence acceptance limits. Three subjects (6.5%)
      reported a total of 4 mild AEs (1 abdominal discomfort and 3 venipuncture
      syncope), which were not considered to be associated with administration of the
      study drug. CONCLUSIONS: This single-dose (20 mg) study found that the test and
      reference formulations of atorvastatin calcium 10-mg tablet met the regulatory
      definition for assuming bioequivalence in these healthy fasted Chinese male
      volunteers. Both formulations were generally well tolerated in the population
      studied. Chinese National Registry Code: 2007L02512.

PMID- 20678687
TI  - Comparison of the bioavailability and tolerability of fixed-dose combination
      glimepiride/metformin 2/500-mg tablets versus separate tablets: A single-dose,
      randomized-sequence, open-label, two-period crossover study in healthy Korean
      volunteers.
AB  - OBJECTIVE: This study compared the bioavailability and tolerability of a fixed
      dose combination (FDC) tablet of glimepiride/metformin 2/500 mg and glimepiride 2
      mg + metformin 500-mg tablets administered separately in healthy Korean subjects.
      METHODS: In this single-dose, open-label, 2-period crossover study, healthy
      Korean volunteers were randomly assigned to receive, in 1 of 2 randomized
      sequences, an FDC tablet of glimepiride/metformin 2/500 mg (test) and glimepiride
      2-mg + metformin 500-mg tablets administered separately (reference), with a 1
      week washout period between treatments. Plasma concentrations of glimepiride and
      metformin were measured using LC/MS-MS. Pharmacokinetic parameters were analyzed
      using noncompartmental methods. Bioequivalence was concluded if the 90% CIs of
      the geometric mean test/reference ratios (GMRs) of the logarithm-transformed
      C(max), AUC from 0 to 30 hours (AUC(0-30)), and AUC(0-infinity) values were
      within the predetermined regulatory range of 80% to 125%. Tolerability was
      assessed using physical examination and laboratory analysis. RESULTS: A total of
      32 subjects were enrolled (16 men [mean (SD) age, 21.8 (2.7) years (range, 18-26
      years); weight, 68.9 (8.3) kg (range, 55.5-85.0 kg)]; 16 women [age, 23.5 (4.5)
      years (range, 20-38 years); weight, 51.7 (3.5) kg (range, 46.8-58.0 kg)]). The
      GMRs (90% CI) of glimepiride C(max), AUC(0-30), and AUC(0-infinity) were 1.01
      (0.91-1.11), 0.98 (0.92-1.03), and 0.97 (0.93-1.04), respectively. For metformin,
      these values were 0.96 (0.87-1.06), 0.96 (0.90-1.03), and 0.96 (0.90-1.03). A
      total of 49 adverse events (AEs) were reported in 10 subjects (31.3%) with the
      FDC and in 13 subjects (40.6%) with the separate tablets. The most commonly
      reported AEs with the test and reference treatments were dizziness (6 [19%] and 7
      [22%]) and sweating (4 [13%] and 7 [22%]), respectively. The severity of all of
      the AEs was considered to be mild, and there were no significant differences in
      the prevalences of AEs between the 2 formulations. CONCLUSIONS: In this study in
      healthy Korean subjects, the requirements for bioequivalence of the
      glimepiride/metformin 2/500-mg FDC and coadministration of separate tablets of
      each drug were met. Both formulations were generally well tolerated.

PMID- 20678688
TI  - Relative bioavailability and pharmacokinetic properties of two different enteric
      formulations of esomeprazole in healthy Bangladeshi male volunteers: An open
      label, single-dose, randomized-sequence, two-way crossover study.
AB  - BACKGROUND: In Bangladesh, a number of generic oral formulations of esomeprazole
      are marketed. Study of the relative bioavailability of these generic formulations
      has yet to be conducted in a Bangladeshi population. OBJECTIVES: The aims of this
      study were to assess the relative bioavailability and pharmacokinetic properties
      of 2 formulations (test and reference) of esomeprazole 40 mg. METHODS: This open
      label, randomized, 2-way crossover study was conducted in healthy Bangladeshi
      male subjects in compliance with the Declaration of Helsinki and International
      Conference on Harmonisation guidelines. Subjects were randomly assigned to
      receive the test formulation followed by the reference formulation or vice versa,
      as a single dose of esomeprazole 40 mg after a 12-hour overnight fast. A washout
      period of 1 week was maintained between treatments. Following oral
      administration, blood samples were collected at 0, 0.5, 0.75, 1, 1.25, 1.5, 1.75,
      2, 2.25, 2.5, 2.75, 3, 3.5, 4, 5, 7, 9, and 12 hour(s) after dosing and analyzed
      for esomeprazole concentrations using a validated HPLC method. Pharmacokinetic
      parameters, including C(max), AUC(0-12), and AUC(0-infinity), were determined
      with a non-compartmental method. The formulations were to be considered
      bioequivalent if the natural log (ln)-transformed ratios of the pharmacokinetic
      parameters were within the predetermined bioequivalence range of 80% to 125%,
      according to the US Food and Drug Administration (FDA) requirement. The within-
      and between-group differences were examined using ANOVA. Tolerability was
      assessed by monitoring vital signs and conducting subject interviews regarding
      adverse events. Interviewers were not blinded to study design. RESULTS: A total
      of 24 nonsmoking, healthy, Bangladeshi male subjects (mean [SD] age, 22.8 [2.22]
      years [range, 20-29 years]; weight, 64.7 [6.9] kg [range, 55-79 kg]; height, 1.69
      [0.05] m [range, 1.63-1.82 m]; and body mass index, 22.39 [2.16] kg/m(2) [range,
      18.99-27.34 kg/m(2)]) were enrolled. From serum data, the mean (SD) values for
      the test and reference products were as follows: 5.26 (1.57) and 5.54 (2.94)
      micromol/L for C(max); 2.53 (0.67) and 2.07 (0.65) hours for T(max); 15.74 (6.50)
      and 16.68 (6.77) micromol/L/h for AUC(0-12); and 17.15 (7.58) and 18.26 (7.31)
      micromol/L/h for AUC(0-infinity), respectively. The mean T(max) was found to be
      significantly different between the test and reference formulations (2.53 [0.67]
      vs 2.07 [0.65] hours, respectively; P < 0.05). The point estimates (90% CI) for
      the test/reference ratios of the In-transformed AUC(0-infinity) and C(max) were
      92.92% (84.02%-102.76%) and 102.36% (85.96%-121.90%), respectively, which were
      within the FDA-accepted limits for assuming bioequivalence. No adverse events
      were reported by the volunteers during the study. CONCLUSION: This single-dose
      study found that the test and reference formulations of esomeprazole 40 mg met
      the FDA regulatory criteria for assuming bioequivalence in these healthy, fasting
      Bangladeshi male volunteers. A significant difference was found in T(max) between
      the 2 formulations. Both formulations were well tolerated in the studied
      population.

PMID- 20678689
TI  - Pharmacokinetics, analgesic effect, and tolerability of a single preprocedural
      dose of intranasal fentanyl in patients undergoing drain removal after breast
      reduction or augmentation surgery: A prospective, randomized, double-blind,
      placebo-controlled study.
AB  - BACKGROUND: Although acetaminophen is used to reduce pain after breast reduction
      or augmentation surgery, pain during the removal of the surgical drains is
      typically not specifically treated. Intranasally administered fentanyl may be
      suitable for pain control during removal of drains. The reported therapeutic
      window of fentanyl is between 0.2 and 1.2 ng/mL. OBJECTIVE: The aim of this study
      was to evaluate the analgesic effect, tolerability, and pharmacokinetics of a
      single preprocedural dose of intranasal fentanyl administered before removal of
      surgical drains in patients who had undergone breast reduction or augmentation
      surgery. METHODS: This was a randomized, double-blind, prospective study in
      healthy women (American Society of Anesthesiologists physical status I or II)
      between the ages of 18 and 65 years who were scheduled to undergo removal of
      surgical drains 1 to 4 days after breast reduction or augmentation surgery. A
      single dose of fentanyl nasal spray 0.05 mg/0.1 mL or placebo (preserved normal
      saline) 0.1 mL was administered 10 minutes before removal of drains. Because
      drain removal is generally carried out without specific analgesia, no rescue
      medication was provided. Pain intensity was measured on a visual analog scale
      (VAS) from 0 = no pain at all to 100 = worst pain possible. Pain intensity was
      evaluated immediately before administration of study medication (t = 0), at the
      time of drain removal (t = 10), and at 15, 20, 25, 40, and 70 minutes after
      administration of study medication. Safety measures included oxygen saturation,
      respiratory rate, heart rate, and blood pressure. Local and systemic adverse
      events were elicited by direct questioning throughout the study. Blood samples
      for pharmacokinetic analysis were collected at baseline and at 5, 10, 15, 30, 60,
      and 120 minutes after administration of study medication. The population
      pharmacokinetic parameters of fentanyl were calculated according to a 1
      compartment open model with an iterative 2-stage Bayesian fitting procedure.
      RESULTS: Thirty-six women were randomized to treatment, and 33 completed the
      study. Their mean (SD) age was 39.2 (13.0) years, and their mean weight was 68.9
      (10.7) kg. Mean VAS scores at baseline were 14.8 (17.8) for the fentanyl group
      and 6.0 (9.7) for the placebo group (P = NS); at the time of drain removal, the
      corresponding VAS scores were 31.0 (20.6) and 33.8 (25.7) (P = NS). Analysis of a
      random-effects model with mean VAS scores as a function of time as the dependent
      variable indicated a significant difference in mean VAS scores between the
      fentanyl and placebo groups (P = 0.006). The overall incidence of adverse events
      was 39.4% (13/33). Among the 17 patients in the fentanyl group, 8 reported > or
      =1 adverse event; among the 16 patients in the placebo group, 9 reported > or =1
      adverse event. A mean estimated C(max) of 0.184 (0.069) ng/mL was reached at
      13.76 (3.56) minutes after administration of intranasal fentanyl. The mean
      measured C(max) was 0.22 (0.088) ng/mL. CONCLUSIONS: In these women who had
      undergone breast reduction or augmentation surgery, a single preprocedural dose
      of intranasal fentanyl was significantly more effective than placebo in reducing
      pain intensity over the hour after removal of surgical drains. However, there was
      no significant difference in pain intensity between fentanyl at the time of drain
      removal and placebo. Intranasal fentanyl was generally well tolerated. At the
      dose used (0.05 mg), plasma fentanyl concentrations were below the reported
      therapeutic window.

PMID- 20678690
TI  - Making sense of basic science in knee and shoulder research.

PMID- 20678691
TI  - Study of rotator cuff repair techniques: we really are trying.

PMID- 20678693
TI  - Treatment of hyperextension.

PMID- 20678694
TI  - Outcome evaluation of ACL reconstruction using patellar tendon allograft.

PMID- 20678698
TI  - Repair of an anteroinferior glenoid defect by the latarjet procedure:
      quantitative assessment of the repair by computed tomography.
AB  - PURPOSE: The purpose of this study was to determine quantitatively whether the
      Latarjet procedure (coracoid transfer to the glenoid) is sufficient to restore a
      significant defect area of the glenoid. METHODS: Fourteen cadaveric shoulders
      were used (mean age, 76 years; range, 72 to 87 years). An anteroinferior glenoid
      defect was created and then the coracoid osteotomized to its angle and
      transferred to the defect. A 3-dimensional computed tomography scan was used to
      calculate the surface area of (1) the intact glenoid, (2) the osteotomized
      glenoid, and (3) the reconstructed glenoid. RESULTS: The mean area of the intact
      inferior glenoid was 734 +/- 89 mm(2). After creation of the defect, the surface
      area of the glenoid was reduced significantly to 523 +/- 55 mm(2) (P = .011). The
      mean defect area was 28.7% +/- 6% of the intact glenoid. After coracoid transfer,
      the mean surface area of the reconstructed glenoid was 708 +/- 71 mm(2) but it
      was not significantly smaller than that of the intact glenoid (P = .274). The
      mean surface area of the coracoid that was used to repair the defect was 198 +/-
      34 mm(2), or 27% +/- 5% of the intact glenoid. CONCLUSIONS: In our cadaveric
      model, a mean 29% defect size of the inferior glenoid was restored to normal
      after coracoid transfer by use of the Latarjet procedure. CLINICAL RELEVANCE: In
      the clinical scenario, the existence of a glenoid bone defect of more than 25% to
      30% is very rare in patients with anterior shoulder instability. Therefore, when
      clinically indicated, large bony defects of the anterior glenoid can be
      adequately treated by the Latarjet procedure.

PMID- 20678699
TI  - Early return to work in workers' compensation patients after arthroscopic full
      thickness rotator cuff repair.
AB  - PURPOSE: The purpose of this study was to investigate the ability of patients to
      return to their preoperative work level and to identify functional prognostic
      factors in a group of Workers' Compensation (WC) patients after arthroscopic
      repair of full-thickness rotator cuff tears at a minimum follow-up of 1 year.
      METHODS: Seventy-eight consecutive WC patients underwent arthroscopic rotator
      cuff repair (ARCR) and were retrospectively reviewed. Potential predictors of
      occupational outcomes were recorded. The primary outcomes included work level at
      the time of discharge, time to maximum medical improvement (MMI), and failures
      requiring revision rotator cuff repair. Secondary outcomes including physical
      examination and subjective scoring scales were also recorded. RESULTS: Overall,
      88.5% of patients (n = 69) returned to their preoperative level of work at a mean
      time to MMI of 7.6 +/- 2.6 months. Of the WC patients, 55 (70.5%) were followed
      up for purposes of assessing shoulder function, with a mean follow-up of 33.6 +/-
      13.9 months. The mean American Shoulder and Elbow Surgeons score at this time was
      82.3 +/- 20.9, and the mean score on a visual analog scale was 1.7 +/- 2.3. An
      association was found between patients who underwent ARCR with open biceps
      tenodesis and delay in MMI (P = .01). CONCLUSIONS: WC patients undergoing ARCR
      may expect a high likelihood of return to full duty at a mean time to MMI of 7.6
      months. At the time of follow-up, patients reported good outcomes using validated
      scoring scales, but subjective outcomes remained inferior to non-WC patients
      based on historical controls. Alcohol use was the only prognostic factor to show
      a significant association with return to restricted-duty employment and repair
      failure. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

PMID- 20678700
TI  - Biomechanical stability of knotless suture anchors used in rotator cuff repair in
      healthy and osteopenic bone.
AB  - PURPOSE: The primary stability of 5 new knotless suture anchors was compared in
      healthy and osteopenic humeri by use of the following anchor systems: Opus Magnum
      2 (ArthroCare, Austin, TX), PushLock (Arthrex, Naples, FL), SwiveLock (Arthrex),
      Kinsa RC (Smith & Nephew, London, England), and Versalok (DePuy Mitek, Raynham,
      MA). METHODS: Twenty healthy and 20 osteopenic, macroscopically intact humeri
      with mean ages of 47 and 72 years, respectively, and mean bone mineral densities
      of 139.8 mg of calcium hydroxyapatite (Ca2+-HA) per milliliter and 51.8 mg of
      calcium hydroxyapatite per milliliter, respectively, were used. Cyclic loading
      was performed to simulate postoperative conditions. The maximum failure load
      (F(max)), the system displacement, and the modes of failure were recorded.
      RESULTS: SwiveLock had the highest mean F(max) in healthy humeri, followed by
      Versalok, PushLock, Kinsa RC, and Opus Magnum 2, with SwiveLock and Versalok
      being statistically superior to Opus Magnum 2. In osteopenic humeri Versalok had
      the highest mean F(max), followed by Opus Magnum 2, SwiveLock, Kinsa RC, and
      PushLock, with no significant differences between all tested anchors. The
      Versalok anchor showed the shortest system displacement in healthy humeri, with
      1.06 mm, and in osteopenic humeri, with 1.47 mm. In healthy humeri the system
      displacement of all anchors lay under the clinical failure threshold of 5 mm. In
      osteopenic humeri the PushLock clearly exceeded the clinical failure threshold,
      with 16.11 mm, whereas the other anchors were notably below the 5-mm threshold,
      with solitary measurements exceeding it. CONCLUSIONS: Every tested anchor
      presented different problems that may lead to premature failure of the rotator
      cuff reconstruction. Knotless suture anchors show differences in primary
      stability depending on the bone quality of the greater tuberosity, the anchorage
      mechanism in the bone, the suture-retaining mechanism, and the anchor design.
      Nevertheless, cortical screw type and subcortical wedging anchors tend to show
      better primary stability than other designs. CLINICAL RELEVANCE: Anchor design
      and bone quality play important roles in the stability of the rotator cuff
      repair.

PMID- 20678701
TI  - Anteromedial elbow arthroscopy portals in patients with prior ulnar nerve
      transposition or subluxation.
AB  - PURPOSE: The purpose of this study was to document management strategies and
      complications relating to the use of anteromedial portals for elbow arthroscopy
      in a series of patients with subluxating or previously transposed ulnar nerves.
      METHODS: A review of 913 elbow arthroscopies showed that 59 elbows with a
      subluxating or previously transposed ulnar nerve required anterior compartment
      arthroscopic surgery. The patients with subluxating nerves had proximal
      anteromedial portals established by reducing and holding the nerve behind the
      epicondyle with a thumb while establishing or entering the portal. In cases of
      prior nerve transposition, the following techniques were used if, by palpation,
      localization of the ulnar nerve was considered to be (1) unequivocal, (2)
      equivocal, or (3) impossible: In group 1 (unequivocal) the proximal anteromedial
      portal was established in the normal antegrade fashion. In group 2 (equivocal) a
      1-cm incision was made at the planned proximal anteromedial portal site and blunt
      dissection down to the capsule was performed without identification of the nerve.
      In group 3 (impossible) a 2- to 4-cm skin incision was made and the nerve was
      identified before placement of the portal. RESULTS: We found that 59 elbows in 56
      patients had a subluxating ulnar nerve (31 elbows) or previous ulnar nerve
      transposition (28 elbows). The transposition had been subcutaneous in 21 and
      submuscular in 7. The proximal anteromedial portal was used in all but 3 cases (2
      patients) of submuscular transposition that were early in the series. In those
      cases only 2 lateral portals were used for anterior compartment surgery. There
      were no operative ulnar nerve injuries related to the use of the proximal
      anteromedial portal. CONCLUSIONS: Neither elbow arthroscopy nor specifically the
      use of the proximal anteromedial portal is contraindicated in patients with prior
      transposition or subluxation of the ulnar nerve. The management of the nerve can
      be based on the degree of certainty with which the nerve can be localized by
      palpation in the region of the planned portal. LEVEL OF EVIDENCE: Level IV,
      therapeutic case series.

PMID- 20678702
TI  - Do complications in hip arthroscopy change with experience?
AB  - PURPOSE: The aim of this study was to evaluate the type and incidence of
      complications during the development of hip arthroscopic techniques. METHODS: A
      retrospective series of 194 files of patients treated with hip arthroscopy in a
      tertiary hospital from December 1999 to March 2008 was reviewed for
      complications. The incidence of complications was recorded consecutively for each
      group of 30 patients and in intervals of 2 years. A comparison between the
      complication rates was performed within the time frames and the set of cases. The
      type and severity of complications were also recorded. RESULTS: There were 12
      complications (6.1%) in this series. Of these, 5 were neurologic (2.6%), 4 were
      musculoskeletal (2%), and 3 were vascular/ischemic (1.5%). According to severity,
      2 were considered major complications (1%), 8 were intermediate (4.1%), and 2
      were minor (1%). The incidence of complications did not change with time (P =
      .959) or with the number of cases performed (P = .771), but different types of
      complications occurred along the learning curve. CONCLUSIONS: The nature of
      complications changed with experience, but no significant variation in the
      incidence was observed over the 9-year period of experience with hip arthroscopy.
      LEVEL OF EVIDENCE: Level IV, therapeutic case series.

PMID- 20678703
TI  - Single-stage anterior cruciate ligament revision with bone-patellar tendon-bone:
      a case-control series of revision of failed synthetic anterior cruciate ligament
      reconstructions.
AB  - PURPOSE: The purpose of this study was to investigate the clinical results of
      single-stage revision anterior cruciate ligament reconstruction (ACLR) after
      synthetic ligament failure. METHODS: The subjects comprised 20 patients who
      underwent revision ACLR after synthetic ligament failure. All revisions were
      performed with bone-patellar tendon-bone graft, and bone tunnel expansion after
      removal of synthetic materials was treated with bone plugs sized and trimmed as
      necessary to fill the bone tunnels. Clinical results were assessed at a mean of
      2.8 years postoperatively, followed by comparison with the results of 20 primary
      ACLRs selected as case-matched controls. Assessment included the Lysholm score,
      International Knee Documentation Committee (IKDC) evaluation, instrumented laxity
      testing, and radiologic examination. RESULTS: Bone tunnel enlargement to 11 mm in
      diameter or greater was found in 10 of 20 revision ACLRs. However, favorable
      anteroposterior stability was obtained at final follow-up (1.4 +/- 2.0 mm in
      revision ACLR group and 1.5 +/- 1.5 mm in primary ACLR group). The overall
      Lysholm score improved significantly from preoperatively to final follow-up, but
      the revision ACLR group showed significantly worse results for the pain parameter
      than the primary ACLR group. The final IKDC results also showed significant
      postoperative improvement, but the number of cases with grade C was significantly
      higher in the revision ACLR group than in the primary ACLR group, which was
      attributed to radiologically confirmed osteoarthritis in the revision ACLR group.
      CONCLUSIONS: Single-stage revision ACLR with bone-patellar tendon-bone graft
      after synthetic ligament failure yielded favorable results in terms of IKDC
      grade, Lysholm score, and anteroposterior stability, despite enlarged bone
      tunnels after removal of synthetic material. Inferior results for the radiologic
      and pain parameters of the IKDC and Lysholm scores were attributed to
      osteoarthritic changes inherent to the revision ACLR group. LEVEL OF EVIDENCE:
      Level III, therapeutic case-control study.

PMID- 20678704
TI  - Differentiation between intraoperative and postoperative bone tunnel widening and
      communication in double-bundle anterior cruciate ligament reconstruction: a
      prospective study.
AB  - PURPOSE: The purpose of this study was to determine the amount of intraoperative
      and postoperative bone tunnel enlargement and communication in double-bundle (DB)
      anterior cruciate ligament (ACL) reconstruction. METHODS: Twenty-four consecutive
      patients undergoing anatomic anteromedial (AM) and posterolateral (PL) 4-tunnel
      DB ACL reconstruction with a 5-strand hamstring graft and extracortical fixation
      were included in a prospective case series. Magnetic resonance imaging scans were
      performed on the second postoperative day and at 7 months' follow up to assess
      intraoperative and postoperative bone tunnel enlargement and communication.
      Tunnel widening was determined in different planes by digitally measuring the
      diameters of the AM and PL bone tunnels. RESULTS: Intraoperative communication of
      the AM bone tunnel with the PL bone tunnel caused by drilling was observed in
      23.8% of patients on the tibia and in no case on the femur. At 7 months
      postoperatively, significant bone tunnel widening occurred at all 4 bone tunnels.
      It was a mean of 20% for the tibial AM bone tunnel, 38% for the tibial PL bone
      tunnel, 34% for the femoral AM bone tunnel, and 46% for the femoral PL bone
      tunnel. Postoperative communication of the AM and PL bone tunnels caused by
      postoperative bone tunnel widening was observed in 19% of patients on the tibia
      and femur. CONCLUSIONS: Intraoperative bone tunnel communication in anatomic DB
      ACL reconstruction was caused by drilling and occurred only on the tibia.
      Significant postoperative bone tunnel widening occurred at all 4 bone tunnels and
      was the highest for the PL bone tunnel. Postoperative bone tunnel communication
      developed in 19% of patients on the tibia and femur and was caused by bone tunnel
      widening. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

PMID- 20678705
TI  - Chondrocyte-seeded type I/III collagen membrane for autologous chondrocyte
      transplantation: prospective 2-year results in patients with cartilage defects of
      the knee joint.
AB  - PURPOSE: We report the 2-year clinical results and identify prognostic factors in
      patients treated with autologous chondrocyte transplantation by use of a collagen
      membrane to seed the chondrocytes (ACT-CS). METHODS: This is a prospective study
      of 59 patients who were treated with ACT-CS and followed up for 24 months.
      Clinical function was assessed by International Knee Documentation Committee
      (IKDC-2000), objective International Cartilage Repair Society, and Lysholm scores
      before surgery and at 6, 12, and 24 months after surgery. RESULTS: On the basis
      of objective International Cartilage Repair Society (ICRS) rating, the percentage
      of patients rated A (normal) and B (nearly normal) increased from 33.9%
      preoperatively to 92.5% at 24 months after ACT-CS. IKDC and Lysholm scores
      increased from 50.1 points (SD, 13.4) and 60.5 points (SD, 9.4), respectively, to
      76.1 points (SD, 15.2) (P < .001) and 82.5 points (SD, 13.7) (P < .001),
      respectively, at 24 months. The failure rate was highest, at 26.7% at 2 years'
      follow-up, in the subgroup of patients who underwent ACT-CS as a salvage
      procedure. The rate of failures in patients with isolated cartilage defects was
      5.9%. CONCLUSIONS: ACT-CS represents a technical modification of membrane
      associated autologous chondrocyte transplantation that combines easy handling and
      attractive application properties with reliable clinical results 24 months after
      surgery, especially in patients with isolated cartilage defects. Even though the
      failure rate was higher in patients with kissing lesions or mild osteoarthritis,
      ACT-CS also seems to improve function in a large proportion of such patients.
      LEVEL OF EVIDENCE: Level IV, prospective case series.

PMID- 20678706
TI  - The relation of the femoral physis and the medial patellofemoral ligament.
AB  - PURPOSE: The purpose of this study was to determine the origin of the medial
      patellofemoral ligament (MPFL) relative to the distal femoral physis by use of an
      indirect radiologic method. METHODS: Twenty radiographs from adolescent male and
      female subjects (10 samples from each group) were used. The subjects studied were
      all skeletally immature, with an open distal femoral physis. The radiographic
      technique described by Schottle et al. was used to identify the origin of the
      MPFL. Imaging software was used to determine the approximate distance of the MPFL
      origin relative to the open growth plate of the subjects involved. RESULTS: In
      all 20 radiographs the medial physis was found to be distal to the average MPFL
      insertion point. The mean location for the female physis was 2.7 +/- 1.1 mm
      distal to the MPFL origin. The mean location for the male physis was 4.6 +/- 2.4
      mm distal to the MPFL origin. CONCLUSIONS: Based on an indirect radiographic
      technique, we found that the origin of the MPFL is just proximal to the femoral
      physis. CLINICAL RELEVANCE: This information may be useful when planning medial
      retinacular surgical procedures in skeletally immature athletes to help avoid
      clinically significant physeal injury.

PMID- 20678707
TI  - Comparison of posterolateral corner reconstructions using computer-assisted
      navigation.
AB  - PURPOSE: This study evaluated different fibular-based reconstruction techniques
      for grade III posterolateral corner (PLC) injuries. METHODS: Seven fresh-frozen
      cadaveric knees were used in this study. A surgical navigation system was used to
      determine varus opening and external rotation at 0 degrees , 30 degrees , and 60
      degrees with a 9.8-Nm varus stress and 5-Nm external rotation stress applied to
      the tibia. Intact and disrupted PLC knees were used as controls. Four different
      fibular-based reconstruction techniques were evaluated. The femoral attachments
      consisted of a single- or double-tunnel technique, and the fibula attachment
      consisted of an anteroposterior or oblique tunnel technique. RESULTS: Sectioning
      of the PLC resulted in an increase in varus and external rotation at all flexion
      angles. All reconstruction techniques restored varus and external rotation
      stability compared with the PLC-deficient state, but the single-femoral tunnel
      reconstruction with an anteroposterior fibular tunnel did not restore varus or
      external rotation stability at 30 degrees and 60 degrees . No reconstruction
      technique overconstrained the knee at any flexion angle. CONCLUSIONS: A double
      femoral tunnel with an oblique fibular tunnel best restored native knee
      kinematics to the lateral side of the knee. CLINICAL RELEVANCE: Although there
      are many different techniques to reconstruct the PLC-deficient knee, this study
      suggests that a single-graft, fibular-based reconstruction that replicates the
      femoral insertions of the lateral collateral ligament and popliteus will be able
      to restore varus and external rotation stability to the knee.

PMID- 20678708
TI  - The expression of proinflammatory cytokines and matrix metalloproteinases in the
      synovial membranes of patients with osteoarthritis compared with traumatic knee
      disorders.
AB  - PURPOSE: The aim of this study was to evaluate a subset of matrix
      metalloproteinases (MMPs) and proinflammatory cytokines within the synovium, from
      traumatic knee disorders (TKDs) and nontraumatic osteoarthritis (OA). METHODS:
      MMP-1, MMP-3, interleukin 1beta, and tumor necrosis factor (TNF) alpha gene
      expression was quantified by use of TaqMan-based real-time polymerase chain
      reaction (Applied Biosystems, Foster City, CA) in synovial tissue samples
      obtained from 12 patients with OA and 32 with TKDs. In addition, the levels of
      serum inflammatory parameter C-reactive protein (CRP) were recorded. At
      arthroscopy, the amount of chondral damage was graded based on the Outerbridge
      classification. RESULTS: Quantitative analysis showed no significant differences
      in the expression levels of MMPs, interleukin 1beta, or TNF-alpha messenger RNA
      between the synovial tissues of patients with OA and TKD, but CRP level was
      significantly increased in the OA group. A significant correlation was also seen
      regarding the gene expression levels between MMP-1 and -3, as well as between CRP
      and MMPs tested. Furthermore, significant relations between TNF-alpha and MMP-1
      plus MMP-3 were observed in the OA synovial tissue. The level of TNF-alpha in the
      synovial tissue correlated with the time after injury as well as chondral damage
      in patients with TKD. CONCLUSIONS: This study shows similar changes in the
      inflammatory patterns of synovial tissue of TKD and OA suggesting a likely
      disease progression. Moreover, the correlation between CRP and MMP expression
      levels indicates their essential role in joint degeneration in synovial tissue of
      primary OA patients. CLINICAL RELEVANCE: TNF-alpha could provide a factor to
      quantify individual risk for the development of OA.

PMID- 20678709
TI  - The effect of interference screw diameter on fixation of soft-tissue grafts in
      anterior cruciate ligament reconstruction.
AB  - PURPOSE: The purpose of this study was to evaluate the effect that interference
      screw diameter has on fixation strength of a soft-tissue anterior cruciate
      ligament (ACL) graft. METHODS: We prepared 32 fresh-frozen bovine tibiae with 9
      mm ACL tibial tunnels. Accompanying 9-mm soft-tissue bovine Achilles grafts were
      also prepared. Bioabsorbable interference screws of increasing diameters were
      used for tibial fixation. There were 4 groups, consisting of 8-, 9-, 10-, and 11
      mm screws for fixation of the 9-mm graft in the 9-mm tunnel. Tensile testing and
      cyclic loading from 50 to 250 N at 2 Hz for a total of 1,500 cycles were
      performed with a hydraulic biaxial materials testing machine. Graft slippage was
      measured with a video analysis technique with photo-reflective markers. At the
      end of cyclic testing, the grafts were loaded to failure, and the ultimate
      strength was recorded. RESULTS: All grafts failed at the tendon-bone-screw
      interface. The ultimate strength (+/- SD) was greatest for the 11-mm screw (624
      +/- 133 N), with slightly decreased strength for the 10-mm (601 +/- 54 N), 9-mm
      (576 +/- 85 N), and 8-mm (532 +/- 185 N) screws. Graft slippage (+/- SD) was
      least for the 9-mm screw (2.65 +/- 2.38 mm). There were no statistically
      significant differences in ultimate strength and graft slippage between screws (P
      = .45 and P = .34, respectively). CONCLUSIONS: All interference screws tested
      provided adequate fixation strength. The results of this study show no
      statistical significance for ultimate strength or graft slippage with variable
      screw diameter. CLINICAL RELEVANCE: Aperture fixation with the interference screw
      technique provides adequate stability for soft-tissue grafts in ACL
      reconstruction. Although no statistical significance was found, there was a trend
      toward less graft-site motion when we used a screw diameter equal to tunnel size.

PMID- 20678710
TI  - Endoscopic distal soft-tissue release in the treatment of hallux valgus: a
      cadaveric study.
AB  - PURPOSE: To study the efficacy and safety of the lateral release of the
      endoscopic distal soft-tissue procedure in the treatment of hallux valgus.
      METHODS: Twenty fresh-frozen foot and ankle specimens were used. Ligament
      sacrificing release was performed in 10 specimens (group 1). Ligament-sparing
      release was performed in another 10 specimens (group 2). The relation between the
      metal rod that passed through the toe web and plantar portal wounds and neural
      structures, degree of completeness of release of the intermetatarsal ligament,
      adductor hallucis insertion, and lateral capsular structures was studied.
      RESULTS: The common digital nerve of the first intermetatarsal space ran along
      the medial side of the rod, the medial digital nerve of the second toe ran
      obliquely and plantar to the rod just proximal to the proximal edge of the
      intermetatarsal ligament, and the lateral digital nerve of the hallux ran along
      the plantar lateral border of the metatarsal head and fibular sesamoid in all
      specimens. The intermetatarsal ligament, adductor hallucis insertion, and lateral
      capsular ligamentous structures were released completely in all specimens in
      group 1. The intermetatarsal ligament was preserved and the lateral capsular
      ligamentous structures were completely released in all specimens in group 2. The
      adductor hallucis insertion was completely released in 7 specimens. No nerve
      injury or cartilage damage was noted in all 20 specimens. CONCLUSIONS: With the
      release of the intermetatarsal ligament, all lateral capsular ligamentous
      structures including the adductor were released, but with intermetatarsal
      ligament preservation, only 70% of the specimens had complete adductor release.
      There was no neural or articular cartilage damage in either group. CLINICAL
      RELEVANCE: The study provides an anatomic basis for safe practice of endoscopic
      distal soft-tissue release in the correction of hallux valgus deformity.

PMID- 20678711
TI  - Arthroscopy classics. SLAP lesions of the shoulder.
AB  - A specific pattern of injury to the superior labrum of the shoulder was
      identified arthroscopically in twenty-seven patients included in a retrospective
      review of more than 700 shoulder arthroscopies performed at our institution. The
      injury of the superior labrum begins posteriorly and extends anteriorly, stopping
      before or at the mid- glenoid notch and including the "anchor" of the biceps
      tendon to the labrum. We have labeled this injury a "SLAP lesion" (Superior
      Labrum Anterior and Posterior). There were 23 males and four females with an
      average age of 37.5 years. Time from injury to surgery averaged 29.3 months. The
      most common mechanism of injury was a compression force to the shoulder, usually
      as the result of a fall onto an outstretched arm, with the shoulder positioned in
      abduction and slight forward flexion at the time of the impact. The most common
      clinical complaints were pain, greater with overhead activity, and a painful
      "catching" or "popping" in the shoulder. No imaging test accurately defined the
      superior labral pathology preoperatively. We divided the superior labrum
      pathology into four distinct types. Treatment was performed arthroscopically
      based on the type of SLAP lesion noted at the time of surgery. The SLAP lesion,
      which has not been previously described, can be diagnosed only arthroscopically
      and may be treated successfully by arthroscopic techniques alone in many
      patients.

PMID- 20678712
TI  - A clinically relevant review of hip biomechanics.
AB  - The hip is a complex anatomic structure composed of osseous, ligamentous, and
      muscular structures responsible for transferring the weight of the body from the
      axial skeleton into the lower extremities. This must be accomplished while
      allowing for dynamic loading during activities such as gait and balance. The
      evaluation of hip pain and periarticular pathology can be challenging because of
      the complex local anatomy and broad differential diagnosis. Recent advancements
      in the evaluation and surgical treatment of hip pathology have led to a renewed
      interest in the management of these disorders. An understanding of the basic
      biomechanical and kinematic function of the hip and the consequences of
      associated pathology can greatly assist the orthopaedic surgeon in appropriately
      diagnosing and treating these problems. In this review we discuss the basic
      biomechanical concepts of the native hip and surrounding structures and the
      changes experienced as a result of various pathologies including dysplasia,
      femoroacetabular impingement, labral injury, capsular laxity, hip instability,
      and articular cartilage injury. We will also discuss the clinical implications
      and surgical management of these pathologies and their role in restoring or
      preserving the native function of the hip joint.

PMID- 20678713
TI  - Subscapularis tendon tears: identifying mid to distal footprint disruptions.
AB  - We present an arthroscopic technique used to identify mid to distal subscapularis
      tendon disruptions. These tears can be easy to miss and require a thorough
      arthroscopic evaluation of the medial biceps sling and the medial side wall of
      the bicipital groove to detect. The arthroscopic procedure is performed with the
      patient in the lateral decubitus position, and the same portals used for standard
      subscapularis repair are used for this technique. If a high degree of clinical
      suspicion exists for subscapularis pathology and no tendon disruption is
      initially identified, an inspection of the medial biceps sling and medial side
      wall of the bicipital groove may show mid to distal subscapularis tendon
      disruptions. A 70 degrees arthroscope is essential in visualizing the medial
      sling, the subscapularis tendon, the biceps tendon, and the proximal 2 cm of the
      bicipital groove. Any disruptions or rents in the medial sling or medial side
      wall are suggestive of a subscapularis tear. Once a tear is identified, we
      proceed with a biceps tenodesis and then take down the medial sling from the
      lesser tuberosity to better delineate the subscapularis footprint. The
      subscapularis may then be repaired in standard fashion.

PMID- 20678714
TI  - Endoscopic treatment of calcinosis circumscripta of the hip joint: a report of 2
      cases of arthroscopic removal of a calcific deposition between the labrum and
      capsule.
AB  - We present 2 cases of arthroscopic removal of a calcific deposition in the form
      of calcinosis circumscripta between the labrum and capsule of the hip joint. Case
      1 was a 42-year-old woman who presented with complaints of a 2-year history of
      right hip pain. Radiographs showed a calcific deposition in the area of the
      acetabular roof. Arthroscopy showed a calcific deposition between the labrum and
      capsule in the form of calcinosis circumscripta. At the 4-month follow up, she
      was symptom free with painless full range of motion. Case 2 was a 48-year-old
      slim woman who presented with complaints of right hip pain over the last 6
      months. Preoperative radiographs showed a hip with a calcific deposition lateral
      to the pronounced acetabular roof. At the 4-month follow up after removal, she
      was also symptom free. To our knowledge, these are the first patients with
      calcinosis circumscripta treated by hip arthroscopy. We recommend the endoscopic
      approach, which is effective and minimally invasive, for treatment of calcinosis
      circumscripta and other calcifications in the hip joint. Especially in young
      patients, with a high activity level and without any symptoms of hip
      osteoarthritis, hip arthroscopy is the ideal treatment.

PMID- 20678715
TI  - Increased survival and reversion of iron-induced cardiac disease in patients with
      thalassemia major receiving intensive combined chelation therapy as compared to
      desferoxamine alone.
AB  - Myocardial iron overload is the leading cause of death in patients with beta
      thalassemia major. An intensification monotherapy with deferoxamine (DFO) as well
      as a combination therapy with DFO and deferiprone (DFP) reduces myocardial iron
      and improves cardiac function. However, the prognosis for thalassemia major
      patients with established cardiac disease switched from DFO monotherapy to
      combined DFP/DFO chelation is unknown. Twenty-eight thalassemia major patients
      with cardiac disease were enrolled in a prospective study lasting 42+/-6 months.
      Fifteen (9 high-ferritin and 6 low-ferritin) were placed on DFP/DFO (DFP, 75
      mg/kg t.i.d.; DFO, 40-50mg/kg over 8-12h at night 5-7 days/week), while 13 (5
      high- and 8 low-ferritin) received DFO alone. No cardiac events were observed
      among high-ferritin patients on combination therapy, whereas 4 cardiac events
      (p=0.0049), including three deaths, occurred in high-ferritin patients on DFO
      monotherapy. These findings demonstrate that in thalassemia major patients with
      well-established cardiac disease combined iron-chelation therapy with DFP/DFO is
      superior to DFO monotherapy.

PMID- 20678716
TI  - Bridging levels of analysis: comment on McClelland et al. and Griffiths et al.

PMID- 20678717
TI  - Neither size fits all: comment on McClelland et al. and Griffiths et al.

PMID- 20678718
TI  - Cognitive effects of topiramate revealed by standardised low-resolution brain
      electromagnetic tomography (sLORETA) of event-related potentials.
AB  - OBJECTIVE: To evaluate the effect of topiramate (TPM) on event-related potentials
      (ERPs) in patients with epilepsy. METHODS: Neuropsychological tests and ERP study
      using auditory oddball paradigm were conducted before and after treatment with
      TPM in drug-naive epilepsy patients. To detect target brain regions in which ERP
      changed during the cognitive task, cortical current densities of ERP components
      were analysed using standardised low-resolution electromagnetic tomography
      (sLORETA). RESULTS: Neuropsychological tests (n=18 patients) showed that TPM
      significantly decreased the score in digit span, Corsi block and Controlled Oral
      Word Association word fluency. Repeated-measures analysis of variance of ERP data
      (n=13 patients) revealed that P2 amplitude was significantly increased at Fz
      electrode following treatment with TPM. Statistical non-parametric map of sLORETA
      between pre- and post-TPM ERPs revealed that current density of P200 component
      was significantly reduced by TPM in bilateral parieto-occipital, temporolimbic
      and dorsolateral right prefrontal regions. CONCLUSIONS: Our findings suggest that
      TPM affects selective brain regions which may be related to cognitive side
      effects. SIGNIFICANCE: Source localisation of ERPs can be helpful in identifying
      target brain regions for the cognitive side effects of anti-epileptic drugs.

PMID- 20678719
TI  - A world in turmoil: chaos, or a new world order?

PMID- 20678720
TI  - Just when you think things can't get any better...

PMID- 20678721
TI  - Denying payments for musculoskeletal ultrasound: how did we get here?

PMID- 20678722
TI  - Radiation safety: have we let the public down?

PMID- 20678723
TI  - Leadership for the ages.

PMID- 20678724
TI  - Can radiology professional society guidelines be converted to effective decision
      support?

PMID- 20678725
TI  - Introduction: quality in diagnostic imaging: learning from worldwide initiatives.

PMID- 20678726
TI  - Radiology provision in the United kingdom: an overview.
AB  - The UK National Health Service (NHS) came into being in 1948, offering health
      care for all, free at the point of access. Over the past 6 decades, the NHS has
      grown to become the world's largest publicly funded health service. The authors
      present an overview of the NHS, from its conception to the present day, with a
      particular emphasis on how the changing environment of the NHS has affected the
      provision of radiologic services. The authors review the current landscape of the
      NHS with regard to radiology provision, from training and research to funding and
      the private sector, and touch on the likely future of the service.

PMID- 20678727
TI  - Improving equitable access to imaging under universal-access medicine: the
      ontario wait time information program and its impact on hospital policy and
      process.
AB  - In Canada, equal access to health care is the goal, but this is associated with
      wait times. Wait times should be fair rather than uniform, taking into account
      the urgency of the problem as well as the time an individual has already waited.
      In November 2004, the Ontario government began addressing this issue. One of the
      first steps was to institute benchmarks reflecting "acceptable" wait times for CT
      and MRI. A public Web site was developed indicating wait times at each Local
      Health Integration Network. Since starting the Wait Time Information Program,
      there has been a sustained reduction in wait times for Ontarians requiring CT and
      MRI. The average wait time for a CT scan went from 81 days in September 2005 to
      47 days in September 2009. For MRI, the resulting wait time was reduced from 120
      to 105 days. Increased patient scans have been achieved by purchasing new CT and
      MRI scanners, expanding hours of operation, and improving patient throughput
      using strategies learned from the Lean initiative, based on Toyota's
      manufacturing philosophy for car production. Institution-specific changes in
      booking procedures have been implemented. Concurrently, government guidelines
      have been developed to ensure accountability for monies received. The Ontario
      Wait Time Information Program is an innovative first step in improving fair and
      equitable access to publicly funded imaging services. There have been reductions
      in wait times for both CT and MRI. As various new processes are implemented,
      further review will be necessary for each step to determine their individual
      efficacy.

PMID- 20678728
TI  - Establishing national medical imaging incident reporting systems: issues and
      challenges.
AB  - Radiology incident reporting systems provide one source of invaluable patient
      safety data that, when combined with appropriate analysis and action, can result
      in significantly safer health care, which is now an urgent priority for
      governments worldwide. Such systems require integration into a wider safety,
      quality, and risk management framework because many issues have global
      implications, and they also require an international classification scheme, which
      is now being developed. These systems can be used to inform global research
      activities as identified by the World Health Organization, many of which
      intersect with the activities of and issues seen in medical imaging departments.
      How to ensure that radiologists (and doctors in general) report incidents, and
      are engaged in the process, is a challenge. However, as demonstrated with the
      example of the Australian Radiology Events Register, this can be achieved when
      the reporting system is integrated with their professional organization and its
      other related activities (such as training and education) and administered by a
      patient safety organization.

PMID- 20678729
TI  - Where failures occur in the imaging care cycle: lessons from the radiology events
      register.
AB  - Adverse events contribute to significant patient morbidity and mortality on a
      global scale, and this has been documented in a number of international studies.
      Despite this, there is limited understanding of medical imaging's involvement in
      such events. Incident reporting is a key feature of high-reliability
      organizations because, understandably, it is essential to know where things go
      wrong and why as the very first step in formulating preventative and corrective
      strategies. Although anesthesiology has led the way, health care in general has
      been slow to adopt this technique, and this includes medical imaging. Knowledge
      as to where medical imaging incidents are initiated and detected, and why, is not
      well documented or appreciated, although this is critical information in relation
      to quality improvement. Using an online radiology reporting system, the authors
      therefore sought to gain further insight and also ascertain where failures are
      located in the imaging cycle, and whether different incidents sources provide
      different information. Last, the authors sought to examine the resilience of the
      imaging system using these incident data.

PMID- 20678730
TI  - Addressing "waste" in diagnostic imaging: some implications of comparative
      effectiveness research.
AB  - Comparative effectiveness research is intended to provide evidence to improve
      patient outcomes through the use of the most appropriate health technology
      affordable. The authors present 5 case studies, focusing on the use of plain
      radiography in common clinical scenarios, to illustrate the considerable scope
      for comparative effectiveness research within medical imaging and the different
      levels of evidence currently in existence to guide the improved use of medical
      imaging. These are blunt ankle injury, breast cancer follow-up, low back pain,
      routine daily chest x-rays in intensive care, and screening for breast cancer.
      Although there are established models for evaluating new technologies, especially
      pharmaceuticals, against the most commonly used current technology, the
      evaluation of technologies in current clinical practice is in an early phase of
      development. Because evaluation resources are limited, one major challenge is
      developing ways to identify established technologies for evaluation to refine the
      indications for their use. A set of criteria with which to identify established
      technologies that may not be delivering value for money is described, and their
      use is illustrated in relation to the 5 case studies. These criteria could be
      incorporated into literature search strategies, stakeholder consultations, and
      utilization scanning. Once identified, these technologies should be formally
      evaluated for their performance in improving patient health without restricting
      the availability of other effective interventions.

PMID- 20678731
TI  - Multidetector CT dose: clinical practice improvement strategies from a successful
      optimization program.
AB  - PURPOSE: The aims of this study were to collect data relating to radiation dose
      delivered by multidetector CT scanning at 10 hospitals and private practices in
      Queensland, Australia, and to test methods for dose optimization training,
      including audit feedback and didactic, face-to-face, small-group teaching of
      optimization techniques. METHODS: Ten hospital-based public and private sector
      radiology practices, with one CT scanner per site, volunteered for the project.
      Data were collected for a variety of common adult and pediatric CT scanning
      protocols, including tube current-time product, pitch, collimation, tube voltage,
      the use of dose modulation, and scan length. A one-day feedback and optimization
      training workshop was conducted for participating practices and was attended by
      the radiologist and medical imaging technologist responsible for the project at
      each site. Data were deidentified for the workshop presentation. During the
      feedback workshop, a detailed analysis and discussion of factors contributing to
      dose for higher dosing practices for each protocol occurred. The postoptimization
      training data collection phase allowed changes to median and spread of doses to
      be measured. RESULTS: During the baseline survey period, data for 1,208 scans
      were collected, and data from 1,153 scans were collected for the postoptimization
      dose survey for the 4 adult protocols (noncontrast brain CT, CT pulmonary
      angiography , CT lumbar spine, and CT urography). A mean decrease in effective
      dose was achieved with all scan protocols. Average reductions of 46% for brain
      CT, 28% for CT pulmonary angiography, 29% for CT lumbar spine, and 24% CT
      urography were calculated. It proved impossible to collect valid pediatric data
      from most sites, because of the small numbers of children presenting for
      multidetector CT, and phantom data were acquired during the preoptimization and
      postoptimization phase. Substantial phantom dose reductions were demonstrated at
      all sites. CONCLUSION: Audit feedback and small-group teaching about optimization
      enabled clinically meaningful dose reduction for a variety of common adult scans.
      However, access to medical radiation physicists, assistance with time-consuming
      data collection, and technical support from a medical imaging technologist were
      costly and critical to the success of the program.

PMID- 20678732
TI  - Advanced search of the electronic medical record: augmenting safety and
      efficiency in radiology.
AB  - The integration of electronic medical record (EMR) systems into clinical practice
      has been spurred by general consensus and recent federal incentives and is set to
      become a standard feature of clinical practice in the US. We discuss how the
      addition of advanced search capabilities to the EMR can improve the radiologist's
      ability to integrate contextual data into workflows associated with both for
      diagnostic and interventional procedures.

PMID- 20678733
TI  - Quality of the written radiology report: a review of the literature.
AB  - PURPOSE: A literature review was carried out, guided by the question, What are
      the important elements of a high-quality radiology written report? METHODS: Two
      papers known to the authors were used as a basis for 5 PubMed search strategies.
      Exclusion criteria were applied to retrieved citations. Reference lists of
      retrieved citations were scanned for additional relevant papers and exclusion
      criteria applied to these. Web sites of professional radiology organizations were
      scanned for guidelines relating to the written radiology report. Retrieved
      guidelines were appraised using the Appraisal of Guidelines for Research &
      Evaluation instrument. Methodologies of retrieved papers were not suitable for
      conventional appraisal, and an evidence table was constructed. RESULTS: The
      search strategy identified 25 published papers and 4 guidelines. Published study
      methodologies included 1 randomized controlled trial; 1 before-and-after study of
      interventions; 10 observational studies, audits, or analyses; 12 surveys; and 1
      narrative review of the literature. CONCLUSIONS: Existing guidelines have a
      number of weaknesses with regard to scope and purpose, methods of development,
      stakeholder consultation, and editorial independence and applicability. There is
      a major gap in published studies relating to testing of interventions to improve
      report quality using conventional randomized controlled trial methods. Published
      studies and guidelines generally support report content, including clinical
      history, examination quality, description of findings, comparison, and diagnosis.
      Important report attributes include accuracy, clarity, and certainty. There is
      wide variation in the language used to describe imaging findings and diagnostic
      certainty. Survey participants strongly preferred reports with structured or
      itemized formats, but few studies exist regarding the effect of report structure
      on quality.

PMID- 20678734
TI  - Don't ignore the "process" to quality improvement.

PMID- 20678735
TI  - A novel hybrid private-academic practice model for a radiology department at a
      community-based medical school.

PMID- 20678736
TI  - MRI: time is dose--and money and versatility.

PMID- 20678737
TI  - William Duane.

PMID- 20678738
TI  - Re: "airport full-body scanners".

PMID- 20678740
TI  - Excluded volume effect and orientational ordering near charged surface in
      solution of ions and Langevin dipoles.
AB  - The influence of a finite volume of ions and orientational ordering of water
      Langevin dipoles on the dielectric permittivity profile in the vicinity of
      charged surface is studied theoretically via a numerical solution of the modified
      Poisson-Boltzmann equation. It is shown that the dielectric permittivity profile
      close to the charged surface is mainly determined by two mechanisms;
      specifically, the depletion of dipoles at the charged surface due to accumulated
      counterions and the increased orientational ordering of the water dipoles.

PMID- 20678741
TI  - Height, education and later-life cognition in Latin America and the Caribbean.
AB  - Building on previous evidence from the U.S., this study investigates the
      relationship between anthropometric markers (height and knee height), early-life
      conditions, education, and cognitive function in later life among urban elderly
      from Latin America and the Caribbean. I document a positive association between
      height and later-life cognitive function, which is larger for women than for men.
      This sex difference increases when I address potential feedback effects from mid-
      and later-life circumstances on stature by using knee height as an instrument for
      height. Specifically, while the estimates for women remain largely unchanged, I
      only find a diminished and statistically insignificant association between
      instrumented height and later-life cognition for men. This finding suggests that
      at least part of the association between height and later-life cognition among
      men may stem from common third factors that are correlated with both height and
      later-life cognition, such as adverse occupational exposures or health events
      during mid- and later life. Extended models that also include education further
      diminish the association between height and later-life cognition. Education
      displays strong positive gradients with the employed measures of childhood
      circumstances - including height - which points to education as a potential
      pathway linking early-life conditions and later-life cognitive function.

PMID- 20678742
TI  - Why are Mexican American boys so much taller now?
AB  - Using NHANES data we find that the difference in average height between non
      Hispanic White and Mexican American boys of ages 2-14 years has decreased 1.7 cm
      on average during the last quarter of the twentieth century in the United States.
      Our hypothesis is that the narrowing of the height gap is related to a larger
      gain in maternal height among Mexican Americans in relation to Whites. We
      estimate a child's height equation and find that on average about 38% of the
      reduction in the gap for boys of ages 2-5 years is attributed to this factor. The
      evidence of a secular trend for height is weak for the case of girls.

PMID- 20678743
TI  - "Survival benefit": the final destination, with still a long way to go.

PMID- 20678744
TI  - [Sjogren's syndrome: Audiological and clinical behaviour in terms of age].
AB  - INTRODUCTION AND OBJECTIVE: To determine the clinical and audiological behaviour
      per age group in Sjogren's Syndrome (SS), considering that it is the second most
      frequent autoimmune rheumatic disease. MATERIAL AND METHOD: The study included 29
      patients with SS with clinical history and audiological studies. The design was
      prospective, descriptive and transversal. RESULTS: Average patient age was 41
      years. All the patients with hearing loss in conventional tone audiometry were of
      the sensory type. At high frequencies, 66% of the patients did not respond at 20
      KHz, and 48% at the frequency of 16 KHz. In logoaudiometry and impedancemetry,
      the results were the ones expected for the auditory thresholds. CONCLUSIONS:
      Auditory damage related to SS is located in the inner ear. Patients must be
      informed by their physician of the risk of having auditory damage as a
      complication of the disease. Audiological evaluation must be performed
      periodically to identify possible audiological damage.

PMID- 20678745
TI  - Impact of prior gestational age at preterm delivery on effectiveness of 17-alpha
      hydroxyprogesterone caproate in practice.
AB  - OBJECTIVE: We sought to examine if 17-alpha-hydroxyprogesterone caproate (17OHPC)
      effectiveness is dependent on the earliest gestational age (GA) at prior
      spontaneous preterm birth (SPTB) when administered in the clinical setting. STUDY
      DESIGN: Women enrolled for outpatient services with current singleton gestation
      and > or =1 prior SPTB between 20-36.9 weeks were identified. Data were divided
      into 3 groups according to earliest GA of prior SPTB (20-27.9, 28-33.9, and 34
      36.9 weeks). We compared GA at delivery of current pregnancy and incidence of
      recurrent SPTB between women enrolled in outpatient 17OHPC administration program
      (n = 2978) and women receiving other outpatient services without 17OHPC (n =
      1260). RESULTS: Rates of recurrent SPTB for those with and without 17OHPC
      prophylaxis, respectively, according to GA at earliest SPTB were: 20-27.9 weeks
      at earliest SPTB, 32.2% vs 40.7%, P = .025; 28-33.9 weeks at earliest SPTB, 34.1%
      vs 45.5%, P < .001; and 34-36.9 weeks at earliest SPTB, 29.3% vs 38.8%, P < .001.
      CONCLUSION: 17OHPC given to prevent recurrent SPTB is effective regardless of GA
      at earliest SPTB.

PMID- 20678746
TI  - Complications of cesarean delivery in the massively obese parturient.
AB  - OBJECTIVE: The objective of the study was to determine predictors of cesarean
      delivery morbidity associated with massive obesity. STUDY DESIGN: This was an
      institutional review board-approved retrospective study of massively obese women
      (body mass index, > or = 50 kg/m(2)) undergoing cesarean delivery. Bivariable and
      multivariable analyses were used to assess the strength of association between
      wound complication and various predictors. RESULTS: Fifty-eight of 194 patients
      (30%) had a wound complication. Most (90%) were wound disruptions, and 86% were
      diagnosed after hospital discharge (median postoperative day, 8.5; interquartile
      range, 6-12). Subcutaneous drains and smoking, but not labor or ruptured
      membranes, were independently associated with wound complication after
      controlling for various confounders. Vertical abdominal incisions were associated
      with increased operative time, blood loss, and vertical hysterotomy. CONCLUSION:
      Women with a body mass index > or = 50 kg/m(2) have a much greater risk for
      cesarean wound complications than previously reported. Avoidance of subcutaneous
      drains and increased use of transverse abdominal wall incisions should be
      considered in massively obese parturients to reduce operative morbidity.

PMID- 20678748
TI  - Clinical features and the risk factors of infantile exotropia recurrence.
AB  - PURPOSE: To evaluate the clinical features and the risk factors of recurrence in
      infantile exotropia. DESIGN: Retrospective, observational case series. METHODS:
      The clinical records of 20 infantile exotropia patients who underwent exotropia
      surgery were reviewed retrospectively. Patients were divided into 2 groups
      according to the amount of exodeviation present at 1 year after surgery.
      Preoperative patient characteristics and postoperative alignments were evaluated
      at 1 day and 1, 3, 6, and 12 months after surgery. RESULTS: The successful group
      was composed of 12 patients with an alignment of less than 10 prism diopters (PD)
      of exodeviation, and the recurrent group was composed of 8 patients with an
      alignment of 10 PD or more of exodeviation (range, 10 to 18 PD) at 1 year after
      surgery. The incidences of dissociated vertical deviation, inferior oblique
      overaction, and rates of constancy before operation were not significantly
      different in the 2 groups (P = .603, P = .158, and P = .347, respectively), and
      postoperative deviations were not significantly different at 1 day after surgery.
      However, postoperative deviations were significantly different in the 2 groups at
      1 month (P = .069) and 3 months (P < .001) after surgery, and this difference was
      maintained at 12 months after surgery. Furthermore, correlation between initial
      alignments at 1 month after surgery and final alignments was significant in
      successful group (P = .012). CONCLUSIONS: No single factor affecting the surgical
      outcome was identified in infantile exotropia, but the recurrence of infantile
      exotropia was apparent from the first postoperative month.

PMID- 20678747
TI  - Intraamniotic infection with genital mycoplasmas exhibits a more intense
      inflammatory response than intraamniotic infection with other microorganisms in
      patients with preterm premature rupture of membranes.
AB  - OBJECTIVE: The objective of the study was to compare the intensity of
      inflammatory responses between intraamniotic infection with genital mycoplasmas
      and intraamniotic infection with other microorganisms. STUDY DESIGN: We examined
      the intensity of intraamniotic and maternal inflammatory responses in 99 patients
      with preterm premature rupture of membranes and a positive amniotic fluid (AF)
      culture. AF was obtained by transabdominal amniocentesis or at the time of
      cesarean delivery. Patients were divided according to the recovered
      microorganisms: (1) genital mycoplasmas (n = 62); (2) other microorganisms (n =
      31); or (3) mixed infection (n = 6). RESULTS: The median AF white blood cell
      (WBC) count, maternal blood WBC count, and plasma C-reactive protein
      concentrations were significantly higher in patients with intraamniotic infection
      with genital mycoplasmas than in those with intraamniotic infection with other
      microorganisms (P < .05 for each). CONCLUSION: Intraamniotic and maternal
      inflammatory responses are more intense in intraamniotic infection with genital
      mycoplasmas than in intraamniotic infection with other microorganisms in patients
      with preterm premature rupture of membranes.

PMID- 20678749
TI  - Visual and systemic outcomes in pediatric ocular myasthenia gravis.
AB  - PURPOSE: To evaluate visual and systemic outcomes in pediatric patients with
      purely ocular myasthenia gravis (OMG) treated at the Children's Hospital of
      Philadelphia. DESIGN: Retrospective chart review. METHODS: Pediatric patients
      with OMG seen at a single institution over a 16-year period with a minimum follow
      up of 1 year were reviewed. Associations of demographic and clinical
      characteristics with disease resolution, amblyopia, and development of
      generalized symptoms of myasthenia gravis were analyzed. RESULTS: Thirty-nine
      patients were identified, with a mean age of 5.4 +/- 4.8 years and mean follow-up
      of 4.8 +/- 4.3 years. Fifteen patients were treated with pyridostigmine only, 19
      (49%) also received steroids, and 15 (38%) underwent thymectomy. Four patients
      (10%) received steroid-sparing immunosuppressive therapy. Resolution occurred in
      10 patients, and generalized symptoms eventually occurred in 9 patients. Although
      10 patients were treated for amblyopia, only 1 had amblyopia at the final visit.
      There was no correlation between sex or age with amblyopia or development of
      generalized symptoms. Thymectomy, when performed before the onset of generalized
      symptoms, showed a trend toward protection from the development of generalized
      symptoms (P = .07). CONCLUSIONS: In our series, 24% of patients had disease
      resolution and 23% had generalized symptoms. Our larger cohort confirms previous
      findings that treated and untreated pediatric patients with OMG have a relatively
      low risk of developing generalized symptoms and that related amblyopia is readily
      reversible. Although our treatments were more aggressive than those previously
      reported, our rates of amblyopia and development of generalized symptoms are
      comparable.

PMID- 20678750
TI  - Use of glaucoma medications: state of the science and directions for
      observational research.
AB  - PURPOSE: To summarize observational studies that focus on the use of glaucoma
      medications and to identify gaps in knowledge to guide future investigation.
      DESIGN: Literature study. METHODS: We searched the electronic databases MEDLINE,
      EMBASE, and PubMed for English language articles published through December 2009
      using the search terms physician's practice patterns, drug prescriptions,
      pharmaceutical services, medication adherence, ophthalmology, glaucoma, and
      ophthalmic solutions. We categorized studies by areas of focus and extracted and
      summarized key features: study population, data sources, and main findings.
      RESULTS: We identified 2224 articles by the search. Fifty-five described glaucoma
      medication use using large databases. Predominant areas of focus were: trends in
      prescription choices (n = 13); adherence, persistence, or both (n = 31); rational
      use of medications (n = 9); and policy-related issues (n = 2). Over the last
      decade, use of beta-blockers and miotics has decreased substantially, whereas new
      agents, particularly prostaglandin analogs, have become more popular.
      Nonadherence was an issue in more than 25% of patients. A significant proportion
      of patients with comorbidities, contraindications, or both had received topical
      beta-blockers. CONCLUSIONS: To date, most studies have focused on adherence to
      glaucoma medications and changes in treatment choices. Major gaps in knowledge
      include prescribing patterns by prescriber specialty (ophthalmologists, primary
      care physicians, and optometrists), medication-related problems, and subsequent
      adverse health outcomes. Well-designed longitudinal observational studies
      addressing these gaps are warranted to improve patient safety.

PMID- 20678751
TI  - An anterior chamber toxicity study evaluating Besivance, AzaSite, and
      Ciprofloxacin.
AB  - PURPOSE: We determined whether Besivance (Bausch & Lomb), AzaSite (Inspire
      Pharmaceuticals, Inc; both with DuraSite bioadhesive [InSite Vision, Inc]) and
      ciprofloxacin are toxic inside the anterior chamber. DESIGN: Randomized, masked,
      placebo-controlled animal study. METHODS: Twenty New Zealand white rabbits (40
      eyes) were randomized to 1 of 4 study groups: Besivance, AzaSite, ciprofloxacin,
      and balanced salt solution. Each eye was injected with 0.1 mL of the study
      medication. Clinical slit-lamp examinations were conducted at 24 and 48 hours
      after injection. All rabbits then were killed and all eyes were enucleated. We
      randomized eyes to either corneal vital staining or histopathologic examination.
      The main outcome measures were clinical and pathologic signs of toxicity.
      RESULTS: The 2 DuraSite-based study groups (Besivance and AzaSite) showed
      clinically and pathologically significant differences when compared with the
      ciprofloxacin and balanced salt solution groups. Besivance and AzaSite eyes
      exhibited significantly similar and severe clinical damage, including severe
      corneal edema. Ciprofloxacin and balanced salt solution eyes appeared very
      similar and had only mild conjunctival injection and limbal vascularity. Vital
      staining and histopathologic evaluation revealed glaucomatous and toxic damage in
      eyes given DuraSite-based medications, whereas non-DuraSite groups showed minimal
      changes. CONCLUSIONS: DuraSite blocks the trabecular meshwork and may be
      additionally toxic when introduced as a large bolus. Until the safety of these
      medications is established with further studies using smaller injected volumes,
      we recommend placement of a suture over a clear corneal wound if DuraSite-based
      medications are used.

PMID- 20678753
TI  - Smoking and schizophrenia independently and additively reduce white matter
      integrity between striatum and frontal cortex.
AB  - BACKGROUND: Although schizophrenia patients are at high risk for tobacco use, the
      neurobiological basis of this comorbid association is not clear. White matter
      abnormalities have been described independently in schizophrenia and smoking
      cohorts. We sought to determine whether smoking and schizophrenia are associated
      with similar white matter abnormalities that could be biomarkers for the high
      risk of smoking in schizophrenia. METHODS: Whole brain white matter integrity
      (fractional anisotropy) was measured in 46 schizophrenia patients (32 smokers and
      14 nonsmokers) and 69 healthy age-matched control subjects (48 smokers and 21
      nonsmokers). RESULTS: Schizophrenia and smoking status were independently and
      additively associated with reduced fractional anisotropy in left anterior
      thalamic radiation/anterior limb of the internal capsule, and significant
      fractional anisotropy decreases were identified in the bilateral uncinate
      fasciculus/inferior fronto-occipital fasciculus in schizophrenia and the left
      prefrontal area in smoking status separately. CONCLUSIONS: Common and distinct
      patterns of impaired white matter are associated with schizophrenia and smoking.
      Particularly, the anatomic congruence of an additive white matter abnormality in
      the anterior thalamic radiation/anterior limb of the internal capsule suggests
      that this abnormal fiber connectivity between frontal cortex and
      striatum/thalamus may be a biomarker for the increased comorbid smoking in
      schizophrenia patients.

PMID- 20678754
TI  - Drug addiction endophenotypes: impulsive versus sensation-seeking personality
      traits.
AB  - BACKGROUND: Genetic factors have been implicated in the development of substance
      abuse disorders, but the role of pre-existing vulnerability in addiction is still
      poorly understood. Personality traits of impulsivity and sensation-seeking are
      highly prevalent in chronic drug users and have been linked with an increased
      risk for substance abuse. However, it has not been clear whether these
      personality traits are a cause or an effect of stimulant drug dependence. METHOD:
      We compared self-reported levels of impulsivity and sensation-seeking between 30
      sibling pairs of stimulant-dependent individuals and their biological
      brothers/sisters who did not have a significant drug-taking history and 30
      unrelated, nondrug-taking control volunteers. RESULTS: Siblings of chronic
      stimulant users reported significantly higher levels of trait-impulsivity than
      control volunteers but did not differ from control volunteers with regard to
      sensation-seeking traits. Stimulant-dependent individuals reported significantly
      higher levels of impulsivity and sensation-seeking compared with both their
      siblings and control volunteers. CONCLUSIONS: These data indicate that
      impulsivity is a behavioral endophenotype mediating risk for stimulant dependence
      that may be exacerbated by chronic drug exposure, whereas abnormal sensation
      seeking is more likely to be an effect of stimulant drug abuse.

PMID- 20678752
TI  - Sex differences in striatal dopamine release in young adults after oral alcohol
      challenge: a positron emission tomography imaging study with [11C]raclopride.
AB  - BACKGROUND: We used a positron emission tomography paradigm with the D2/3
      radiotracer [11C]raclopride and an alcohol challenge to examine the magnitude of
      alcohol-induced dopamine release and compare it between young men and women.
      METHODS: Twenty-one nonalcohol-dependent young social drinkers completed two
      positron emission tomography scans on separate days following ingestion of a
      juice mix containing either ethanol (.75 mg/kg body water) or trace ethanol only.
      The extent of dopamine released after alcohol was estimated by the percentage
      difference in [11C]raclopride binding potential (DeltaBP(ND)) between days.
      RESULTS: Alcohol administration significantly displaced [11C]raclopride in all
      striatal subregions, indicating dopamine release, with the largest effect
      observed in the ventral striatum. Linear mixed model analysis across all striatal
      subregions of regional DeltaBP(ND) with region of interest as repeated measure
      showed a highly significant effect of sex (p < .001). Ventrostriatal dopamine
      release in men, but not in women, showed a significant positive correlation to
      alcohol-induced measures of subjective activation. Furthermore, we found a
      significant negative correlation between the frequency of maximum alcohol
      consumption per 24 hours and ventrostriatal DeltaBP(ND) (r = .739, p = .009) in
      men. CONCLUSIONS: This study provides definitive evidence that oral alcohol
      induces dopamine release in nonalcoholic human subjects and shows sex differences
      in the magnitude of this effect. The ability of alcohol to stimulate dopamine
      release may contribute to its rewarding effects and, thereby, to its abuse
      liability in humans. Our report further suggests several biological mechanisms
      that may mediate the difference in vulnerability for alcoholism between men and
      women.

PMID- 20678755
TI  - No correlation between childhood maltreatment and telomere length.

PMID- 20678757
TI  - The influence of beta-cyclodextrin on acid-base and tautomeric equilibrium of
      fluorescein dyes in aqueous solution.
AB  - The protolytic equilibrium of fluorescein in aqueous solutions was studied in the
      presence of cycloheptaamylose (beta-cyclodextrin, or beta-CD). The constants of
      stepwise ionization of the dye (H(3)R(+)left arrow over right arrowH(2)Rleft
      arrow over right arrow HR(-)left arrow over right arrowR(2-)), K(a0), K(a1), and
      K(a2) were determined using vis-spectroscopy at ionic strength 0.05 M
      (NaCl+buffer) and 25 degrees C. In the presence of 0.0086 M beta-CD, the indices
      of ionization constants are as follows: pK(a0)=1.21+/-0.12, pK(a1)=5.08+/-0.03,
      pK(a2)=6.35+/-0.02. The changes in these pK(a)s, as compared with the values
      determined without cyclodextrin, are unequal. Namely, the pK(a0) value decreases
      by 1.0, while the pK(a1) value increases by 0.7. Thus, the introduction of beta
      CD allows to govern the ratios K(a0)/K(a1) and K(a1)/K(a2), which are equal to,
      respectively, 141 and 151 in water, and 7.4 x 10(3) and 18.6 with cyclodextrin
      added. Rationalization of the observed phenomenon is possible taking into account
      the detailed scheme of protolytic equilibrium. Conclusions concerning tautomerism
      of dye molecules were deduced from absorption spectra; the fractions of
      tautomers, tautomerization constants, and microscopic ionization constants were
      evaluated. These data allow concluding that the main reason for the
      aforementioned pK(a) alterations is the binding of H(2)R by the cyclodextrin
      cavity accompanied by turning these neutral species into the colorless lactone.
      The host-guest interaction of neutral species of fluorescein isothiocyanate, 2,7
      dichlorofluorescein, and 3',4',5',6'-tetrachlorofluorescein also results in the
      cyclodextrin-assisted shift of tautomeric equilibrium. Such nature of
      interactions is proved by the addition of competing agents, camphor-4-carboxylic
      acid and sodium n-nonylsulfonate, which results in the removing of neutral dye
      species from the cycloheptaamylose cavity.

PMID- 20678758
TI  - Differences in natural killer cell quantification and receptor profile expression
      in HIV-1 infected Chinese children.
AB  - Natural killer (NK) cells are believed to play a role in the progression of human
      immunodeficiency virus 1 (HIV-1) disease, and NK cell levels are reduced in
      individuals with chronic HIV-1 infection. To assess the effects on quantity of NK
      cells and the changes of NK cell receptors in HIV-1 infected children via mother
      to-child transmission, the percentage of NK cells is quantified and the changes
      in the NK cell receptor profiles in 20 HIV-1 infected children who are not
      progressing into AIDS were examined. The results showed that NK cell percentage
      was decreased in the HIV-1 infected children. The expression of NKp30 on NK cells
      was increased, while the expressions of CD16, NKp44, NKp46, NKp80, NTB-A, CD244,
      KIR2D, KIR3DL1 and NKG2D on NK cells were decreased in the HIV-1 infected
      children. NK cell cytolytic activity was elevated in HIV-1 infected children.
      These results indicate that the acute changes in NK cell percentage and NK cell
      receptors in HIV-1 infected children are different from the HIV-1 infected adult
      individuals. Moreover, serum concentrations of IL-18 were elevated in HIV
      infected children compared to HIV-uninfected controls. These differences probably
      play a role in protecting against transmission of maternal HIV-1 virus and
      guiding the therapeutic strategies for HIV-1 infected children.

PMID- 20678756
TI  - Stereological approaches to identifying neuropathology in psychosis.
AB  - The challenges involved in identifying the neuropathological substrates of the
      clinical syndrome recognized as schizophrenia are well known. Stereological
      sampling provides a means to obtain accurate and precise quantitative estimates
      of components of neural circuits and thus offers promise of an enhanced capacity
      to detect subtle alterations in brain structure associated with schizophrenia. In
      this review, we 1) consider the importance and rationale for robust quantitative
      measures of brain abnormalities in postmortem studies of schizophrenia; 2)
      provide a brief overview of stereological methods for obtaining such measures; 3)
      discuss the methodological details that should be reported to document the
      robustness of a stereological study; 4) given the constraints of postmortem human
      studies, suggest how to approach the limitations of less robust designs; and 5)
      present an overview of methodologically sound stereological estimates from
      postmortem studies of schizophrenia.

PMID- 20678759
TI  - Developmental dissociations between lexical reading and comprehension: evidence
      from two cases of hyperlexia.
AB  - We report two cases of developmental hyperlexia - JY and AD - who performed at
      normal levels or above in converting print into speech, but who were very
      impaired in spoken and written word comprehension. Our investigations focussed on
      whether these cases displayed evidence for normal acquisition of lexical reading
      skills, as indexed by unimpaired performance for age in reading aloud a set of
      irregular words, despite poor acquisition of semantic knowledge of the same
      words. In both cases, this dissociation was evident. The pattern of results was
      also demonstrated at an item level: the two cases showed no significant
      differences in reading accuracy for irregular words which they could define than
      for those which they could not. The results provide further evidence for the
      existence of a direct-lexical route from orthography to phonology, which is not
      necessarily mediated by semantic knowledge.

PMID- 20678760
TI  - Auditory temporal processing and dyslexia in an orthographically consistent
      language.
AB  - We examined two hypotheses relating auditory processing to dyslexia in Greek, an
      orthographically consistent language. Study I examined the "P-center" or "beat
      detection" hypothesis (Goswami et al., 2002) in a sample of Grade 6 dyslexics,
      Grade 6 chronological age (CA) controls, and Grade 4 reading age (RA) controls.
      Study II examined the "temporal processing," or "rapid auditory processing"
      hypothesis (Tallal, 1980) in a sample of Grade 7 dyslexics, CA controls, and in
      two groups of CA matched children with low frequency discrimination or low tone
      sequencing performance. Both studies indicate that (a) as a group, dyslexic
      children did not perform significantly worse on auditory processing measures than
      the control groups; (b) measures of auditory processing mostly did not account
      for unique amount of variance in phonological processing, reading, or spelling;
      and (c) at an individual level of analysis, some of the dyslexic children
      experienced auditory temporal processing deficits. Implications on the importance
      of auditory processing in reading in orthographically consistent languages are
      discussed.

PMID- 20678761
TI  - Line bisection in homonymous visual field defects - Recent findings and future
      directions.
AB  - Homonymous visual field defects are a frequent consequence of brain damage
      occurring in some 20-40% of stroke patients. They are often accompanied by a
      peculiar spatial bias termed "Hemianopic Line Bisection Error" (HLBE). Although
      known for more than 100 years the explanations for the HLBE put forward remain
      controversial. One explanation holds that the HLBE is a direct consequence of the
      field defect itself and reflects a compensatory shift of attention towards the
      scotoma. Another, contradicting position states that although the HLBE is
      frequently found in any type of homonymous visual field defect - not only
      hemianopia - it is not simply a direct consequence of the field defect itself,
      although it does contribute to it. According to this position, the HLBE arises
      from additional damage to extrastriate cortex, thus causing the spatial bias
      towards the blind field. In the present article we summarize the main arguments
      of both theoretical positions and argue that although both accounts are valid,
      they are incomplete and several important issues remain unresolved. These include
      the potential contribution of eccentric fixation to the HLBE, the question of
      multimodal impairments, the role of (visuo)-motor processes, the relation between
      the HLBE and visual field recovery, and the exact clinical significance of the
      HLBE. Thus, far from concluding the research on the line-bisection error in
      hemianopia, the recent series of publications on this topic serve as a welcome
      reminder of how much more research is needed.

PMID- 20678762
TI  - [Mortality prognosis factors in heart failure in a cohort of North-West Spain.
      EPICOUR study].
AB  - AIMS: Heart failure (HF) is a serious health problem in Spain because it has a
      high mortality rate and causes considerable costs to the health-care system. This
      paper presents a study made in the Spanish province of Ourense to study the
      survival of patients with HF related to the ventricular function or other
      possible risk factors (RF) associated with the HF prognosis. MATERIAL AND
      METHODS: A prospective cohort study was performed, considering any patient
      hospitalized due to HF from 1 January 1999 to 31 December 2002 (5318 patients)
      who had undergone an echocardiography that showed systolic or diastolic
      dysfunction as potential participants (2387 patients). After at least 24 months
      of the index episode of hospitalization, a sample of 2384 patients was chosen by
      random sampling. The principal measurement was based on survival and the
      differences observed in the performance of the left ventricular ejection
      fraction, of functional class (FC) of HF and of other clinical and
      epidemiological characteristics. The Kaplan-Meier, log-rank and Cox tests were
      used. RESULTS: Mean age of the patients 74.84 (range 36-95); 53.4% males and
      56.5% first admission. The most common antecedent was arterial hypertension (HTA)
      (59.9%), followed by valvulopathy (41.9%) and heart disease (HD) (26.8%). A total
      of 44.3% of the patients had atrial fibrillation-flutter (AF). Global survival at
      5 years was 47.9% and specific survival rate for HF was 74.8%. There were no
      significant differences in survival between patients with heart failure and
      preserved systolic function (HF-PSF) and those who suffered systolic dysfunction
      (p=0.248). Prognostic factors of mortality in patients with HF are: advanced
      functional class (class III-IV) prior to admission (Hazard ratio [HR] 5.37),
      deterioration of the glomerular filtration rate (GFR) (HR 0.98), hypoalbuminemia
      (HR 0.59), hyponatremia (HR 0.93) and hyperkalemia (HR 1.79). The Castelli index
      higher than 4.5 is in the limit of statistical significance. CONCLUSIONS: Global
      survival rate observed at 5 years of research is similar to the results found in
      already-published papers. Specific survival rate for HF is lower and there are no
      differences in the survival rate with regard to the left ventricle ejection
      fraction (E(f)). However, we show that hypoalbuminemia, hyperkalemia and high
      Castelli index are important prognostic factors of mortality in patients with HF.

PMID- 20678763
TI  - Efficacy and safety of ovarian stimulation before chemotherapy in 205 cases.
AB  - Ovarian stimulation and cryopreservation of fertilized oocytes before cancer
      therapy is the best established and efficient fertility preservation technique
      and should still be considered before chemotherapy. Within a short time frame of
      2 weeks, between 8.6 (18-25 y) and 5.1 (36-40 y) fertilized oocytes can be
      cryopreserved.

PMID- 20678764
TI  - Incidence and predictors for the need for fasciotomy after extremity trauma: a 10
      year review in a mature level I trauma centre.
AB  - BACKGROUND: Compartment syndrome is a devastating complication after trauma to
      the extremities. Prompt fasciotomy is essential for avoiding disability and limb
      loss. The purpose of this study was to determine the incidence and predictors for
      the need for fasciotomy after extremity trauma. METHODS: All trauma patients
      sustaining extremity injuries admitted to the LAC+USC Medical Centre during a 10
      year period ending in December 2007 were identified. Demographics, clinical data,
      blood requirements and outcomes were abstracted. Patients who required an
      extremity fasciotomy were compared with those who did not. Stepwise logistic
      regression analysis was used to identify independent predictors of the need for
      fasciotomy. RESULTS: During the study period, 288 (2.8%) of a total of 10,315
      patients who sustained extremity trauma required a fasciotomy. Despite a stable
      ISS and extremity AIS over the study period, fasciotomy rates decreased
      significantly from 3.2% in 1998 to 2.5% in 2002 to 0.7% in 2007 (p<0.001). The
      need for fasciotomy varied widely by mechanism of injury (from 0.9% after motor
      vehicle accident to 8.6% in GSWs, p<0.001) and by type of injury (from 2.2% in
      closed fracture to 41.8% in combined vascular injury, p<0.001). Patients
      requiring fasciotomy were predominantly male (90.6% vs. 73.5%, p<0.001) and had
      higher ISS (14.5+/-9.7 vs. 12.8+/-10.6, p=0.006). Patients requiring fasciotomy
      received significantly more units of PRBCs (8.2+/-13.9 vs. 1.8+/-5.1, p<0.001)
      during their hospital stay. Patients requiring fasciotomy were more likely to
      sustain open fractures (upper: 8.3% vs. 5.2%, p=0.031 and lower: 28.5% vs. 11.8%,
      p<0.001); joint dislocations (elbow: 25.0% vs. 8.3%, p=0.005, and knee: 31.2% vs.
      6.5%, p<0.001) and brachial (8.0% vs. 1.1%, p<0.001), femoral (20.1% vs. 1.1%,
      p<0.001) and popliteal vessel injuries (15.3% vs. 0.4%, p<0.001). A stepwise
      logistic regression identified the presence of vascular injury, need for PRBC
      transfusion, male gender, open fracture, elbow or knee dislocation, GSW, ISS>=16
      and age<55 years as independent predictors for the need for fasciotomy.
      CONCLUSION: After extremity trauma, approximately 1% of patients will require a
      fasciotomy. The need for fasciotomy varied widely by injury mechanism and type
      reaching 42% in patients who sustained a combined arterial and venous injury. The
      above risk factors were identified as independent predictors for the need for
      fasciotomy.

PMID- 20678765
TI  - Femoral nailing during serum bicarbonate-defined hypo-perfusion predicts
      pulmonary organ dysfunction in multi-system trauma patients.
AB  - OBJECTIVE: To assess the value of venous serum bicarbonate as an endpoint of
      resuscitation and guide to timing of femoral nailing in multi-system trauma
      patients. DESIGN: Retrospective cohort study. SETTING: Academic Level 1 Trauma
      Centre. PATIENTS: Seventy-two consecutive adult multi-system trauma patients
      (Injury Severity Score>=15) with femoral shaft fracture (Orthopaedic Trauma
      Association Class 32-A to 32-C) treated with reamed medullary nail fixation.
      INTERVENTION: Femoral nailing in the setting of hypo-perfusion defined by venous
      serum bicarbonate (SB). Threshold values of SB were determined first by
      correlating SB and simultaneously drawn arterial base deficit (BD). Then,
      corresponding values of SB to previously defined thresholds of hypo-perfusion
      based on BD were identified using regression analysis. MAIN OUTCOME MEASUREMENT:
      Pulmonary organ dysfunction (POD) component of the Denver Multiple Organ Failure
      scoring system. RESULTS: Simultaneous admission SB and BD values were correlated
      (r=-0.43, p=0.001). Adjusting for age, ISS and baseline POD, patients with
      SB<24.7 mequiv./L within 6 h of treatment had a 12-fold increase in POD (OR 12.2,
      95% CI 1.5-98.6, p=0.019). This association was diminished, but still significant
      with hypo-perfusion present within 12 h prior to treatment (OR 5.6, 95% CI 1.0
      29.1, p=0.042) and 24 h prior to treatment (OR 5.9, 95% CI 1.1-30.7, p=0.037).
      CONCLUSIONS: Medullary fixation of femoral shaft fracture in the setting of serum
      bicarbonate-defined hypo-perfusion is associated with increased morbidity.
      Appropriate damage-control measures and aggressive resuscitation prior to
      definitive fracture care are advised and physiologic markers such as serum
      bicarbonate should guide clinical decision making rather than temporal
      distinctions.

PMID- 20678766
TI  - Identifying predictors of early non-recovery in a compensation setting: The
      Whiplash Outcome Study.
AB  - CONTEXT: People with Whiplash Associated Disorder (WAD) often experience pain and
      disability for extended periods of time. A large proportion of these people will
      seek treatment through a compensation process. Rarely is data related to people's
      health collected within the compensation process making it difficult to identify
      those that are at risk of delayed recovery and appropriately direct
      interventions. STUDY OBJECTIVE: To compare people with WAD who have recovered
      with those that have not, within 3 months of injury and identify potential
      predictors of poorer health and non-recovery to inform claim screening processes.
      STUDY DESIGN: Cross-sectional analysis of a cohort study. PARTICIPANTS: People
      who sustained a WAD and claimed compensation within an Australian Motor Accidents
      Compensation Scheme between November 2007 and June 2009. MEASURE OF RECOVERY:
      Functional Rating Index (FRI) score (25). HEALTH OUTCOME MEASURES: Short Form 36
      (SF36), FRI, and the Pain Catastrophising Scale (PCS). METHODS: 246 people who
      had lodged a claim for compensation were enrolled in the Whiplash Outcome Study
      within 3 months of sustaining a WAD injury. Participants were assigned to a
      recovered or non recovered group and analysed for differences between the two
      groups. Multiple linear regression models were used to identify potential
      predictors of poorer health and non-recovery. RESULTS: Overall 23% of the study
      population had recovered within 3 months of sustaining a WAD, whilst only 9% had
      finalised their insurance claim. The recovered group had significantly better
      scores on all health outcome measures; SF36 Physical Component Score, SF36 Mental
      Component Score and the PCS(p < 0.001). The significant independent predictors of
      poorer health and non-recovery were helplessness(p < 0.001), older age (p <
      0.001) and pre-injury work status being affected (p < 0.001) (r(2) =
      .624).Regardless of the health outcome measure used, helplessness was
      significantly associated with poorer reported health. CONCLUSION: Including
      additional information at claim notification, specifically the PCS and
      information on the effect the injury has on the working population could
      significantly improve claim screening processes, identifying those with poorer
      health and risk of non-recovery.

PMID- 20678767
TI  - Fetal facial sonographic markers for second trimester Down syndrome screening in
      a Thai population.
AB  - OBJECTIVE: To assess the efficacy of using facial sonographic markers for
      screening fetuses in the second trimester for Down syndrome (DS) in a high-risk
      Thai population. METHOD: Frontomaxillary facial angle (FMF) and nasal bone length
      (NBL) were measured prospectively in pregnant women at high-risk for DS who were
      undergoing genetic amniocentesis from November 2008 to October 2009. The receiver
      operator characteristic (ROC) curves were constructed to assess the screening
      efficacy of FMF angle and NBL. RESULT: A total of 460 pregnant women were
      recruited, and a mid-sagittal facial profile was obtained for 403 fetuses. There
      were 386 fetuses with normal chromosomes, 10 fetuses with DS, 1 fetus with
      trisomy 13, and 1 fetus with trisomy 18. The remaining 5 fetuses had balanced
      translocation (n = 2), deletion (n = 1), and mosaic Turner (n = 2). Two different
      combinations of FMF angle and biparietal diameter to nasal bone length (BPD:NBL)
      ratio for DS screening in the second trimester achieved 50% and 90% detection
      rates and 4.4% and 14.0% false positive rates, respectively. CONCLUSION: The
      combination of FMF angle and BPD:NBL ratio has a high sensitivity and specificity
      for screening for DS in the second trimester in a high-risk Thai population.

PMID- 20678768
TI  - Illness perceptions and adherence to therapeutic regimens among patients with
      hypertension: a structural modeling approach.
AB  - BACKGROUND: Patients' lay views of illness are influential on adherence to
      therapeutic regimes. However, factors associate with non-adherence are not
      examined simultaneously. OBJECTIVES: The purpose of the study was to test a
      hypothetical model of the relationships between illness perception and adherence
      to prescribed medication and self-management recommendations of hypertensive
      patients based on theoretical assumptions of the Common-Sense Model. DESIGN: A
      cross-sectional, descriptive, correlational design. SETTINGS: Cardiovascular
      clinics of three teaching hospitals in central Taiwan. PARTICIPANTS: Three
      hundred and fifty-five hypertensive patients. METHODS: Data were collected
      through face-to-face interviews using structured questionnaires, including the
      Illness Perception Questionnaire-Revised, the Medication Adherence Inventory, and
      the Inventory of Adherence to Self-Management. Data were analyzed by structural
      equation modeling using LISREL. RESULTS: The findings suggested that the illness
      identity may directly affect patient adherence to prescribed medications or
      indirectly affect patient adherence via control of the disease and cause. Control
      of the disease exhibited direct effects on adherence to prescribed medications
      and self-management, while the cause of the illness only showed direct effects on
      adherence to prescribed medications. The relationships were independent of
      systolic blood pressure, age, the total number of antihypertensive medication,
      and comorbidity. CONCLUSIONS: The findings of the study extend the utility of the
      Common-Sense Model, suggesting that adherence to therapeutic regimens may be
      enhanced by improving a sense of controllability. For patients who experience
      symptoms related to high blood pressure, barriers to adherence may be reduced by
      assessing and clarifying the meaning of illness identity and causal attributions.

PMID- 20678769
TI  - A cross-sectional survey of self-perceived health status and metabolic control
      values in patients with type 2 diabetes.
AB  - BACKGROUND: The prevalence of diabetes is increasing worldwide. Diabetes and
      other chronic disorders play an important role in how patients perceive their
      health status, this perception being an important component of general health.
      OBJECTIVES: The purpose of this study is to determine self-perceived health
      status and metabolic control in patients with type 2 diabetes and to understand
      the relationship between perceived health status and metabolic control in
      diabetic participants. DESIGN: This is a cross-sectional survey. SETTING: The
      research population was diabetes sufferers registered with the Turkish Diabetes
      Society in Denizli Province, Turkey. PARTICIPANTS: A convenience sample composed
      of 110 patients with type 2 diabetes mellitus. METHODS: The research data were
      collected using three tools. The first of these was a "Socio-demographic Data
      Form" to gather information on the diabetes patients. The second was a survey on
      the patients' self-perceived health (how do rate your state of health in general)
      in which the patients were asked to rate their own health in one of five
      categories: very good, good, fair, bad and very bad. For the statistical
      analysis, the study group was divided into two groups: "good", consisting of
      those who classified their health as either very good or good; and "poor", those
      who gave other responses. The third type of data was collected by measuring
      metabolic control outcomes [glycosylated hemoglobin (HbA(1C)), fasting blood
      sugar (FBS), non-fasting blood sugar, total cholesterol, high-density
      lipoproteins (HDL) and triglycerides] for each participant. RESULTS:
      Approximately half of the diabetic participants surveyed have poor self-perceived
      health. In terms of the values of HbA(1C), an important indicator of metabolic
      control levels, it was found that only 24.5% of the participants surveyed had
      good metabolic control. There was found to be a statistically significant
      difference between self-perceived health and levels of HbA(1C); 68% of
      participants who had high HbA(1C) values evaluated their health as good, whereas
      63.9% of those who had poor HbA(1C) values evaluated their health as bad. Age,
      level of education, mode of treatment, adherence to treatment and level of
      exercise were factors that were found to have statistically significant
      differences from, and therefore an influence on, self-reported health.
      CONCLUSION: When working with diabetes patients, as soon as the diagnosis has
      been made, it is recommended that information both on subjective perceptions of
      health and on perceptions of the illness (health perceptions, health beliefs
      related to the illness) are evaluated and objective data (metabolic control
      values) are gathered.

PMID- 20678770
TI  - "Like a trip to McDonalds": a grounded theory study of patient experiences of day
      surgery.
AB  - BACKGROUND: The amount and complexity of (ambulatory) day surgery is rapidly
      expanding internationally. Nurses have a responsibility to provide quality care
      for day surgery patients. To do this they must understand all aspects of the
      patient experience. There is dearth of research into day surgery using a
      sociological frame of reference. OBJECTIVE: The study investigated patients'
      experiences of day surgery using a sociological frame of reference. DESIGN: A
      qualitative study using the grounded theory approach was used. SETTING: The study
      was based in two day surgery units in two urban public hospitals in the United
      Kingdom. PARTICIPANTS: 145 patients aged 18-70 years and 100 carers were
      purposely selected from the orthopaedic, ear nose and throat and general surgical
      lists. They were all English speaking and were of varied socio-economic
      background. METHODS: The data was collected from 2004 to 2006. Semi-structured
      interviews were conducted on three occasions: before surgery, 48 h following
      surgery and one month following discharge. Permission was received from the Local
      Research Ethics Committee. Analysis of the data involved line-by-line analysis,
      compilation of key words and phrases (codes) and constant comparison of the codes
      until categories emerged. FINDINGS: Patients liked day surgery and placed it
      within the wider societal context of efficiency and speed. Time was a major issue
      for them. They wished surgery, like all other aspects of their life to be a
      speedy process. They likened it to a McDonald's experience with its emphasis on
      speed, predictability and control. CONCLUSION: This study throws new light on
      patient experiences and offers an understanding of day surgery against a western
      culture which emphasises the importance of speed and efficiency. It is a popular
      choice for patients but at times it can be seen to be a mechanistic way of
      providing care. The implications for nurses to provide education and information
      to add to the quality of the patient experience are discussed.

PMID- 20678771
TI  - Micronutrient-enriched rapeseed oils reduce cardiovascular disease risk factors
      in rats fed a high-fat diet.
AB  - Many epidemiological studies have demonstrated that vegetable food consumption is
      associated with a reduced risk of cardiovascular diseases. The beneficial effects
      have been attributed to the content of bioactive molecules present in large
      quantities in plant food. The main proposal of this study was to evaluate in vivo
      whether micronutrient-enriched rapeseed oils (optimised oils) obtained using
      different crushing and refining procedures and characterised by different
      quantities and qualities of micronutrients, could have any beneficial effect on
      lipid profile and antioxidant status of plasma and liver. Sprague-Dawley rats
      were fed a high-fat diet for 4 weeks. The lipid source consisted of 20% optimised
      rapeseed oils with different quantities and qualities of micronutrients. The
      control group received traditional refined rapeseed oil. The experimental
      optimised oils all had a hypolipidaemic effect. In the group fed the highest
      levels of micronutrients, the reduction in plasma and hepatic triglycerides
      reached 25% and 17%, respectively, that of cholesterol 20% and 14%, respectively.
      In plasma, the ferric antioxidant capacity, superoxide dismutase, glutathione
      peroxidase and reduced glutathione significantly increased and lipid peroxidation
      decreased in parallel with the enhancement of micronutrients. The same trend was
      observed in the liver, except for glutathione peroxidase which was not affected
      by optimised oils. These results indicate that a regular intake of optimised
      rapeseed oils can help to improve lipid status and prevent oxidative stress,
      providing evidence that optimised oils could be a functional food with
      potentially important cardioprotective properties.

PMID- 20678772
TI  - A mechanistic study for strain rate sensitivity of rabbit patellar tendon.
AB  - The ultrastructural mechanism for strain rate sensitivity of collagenous tissue
      has not been well studied at the collagen fibril level. Our objective is to
      reveal the mechanistic contribution of tendon's key structural component to
      strain rate sensitivity. We have investigated the structure of the collagen
      fibril undergoing tension at different strain rates. Tendon fascicles were pulled
      and fixed within the linear region (12% local tissue strain) at multiple strain
      rates. Although samples were pulled to the same percent elongation, the fibrils
      were noticed to elongate differently, increasing with strain rate. For the 0.1,
      10, and 70%/s strain rates, there were 1.84+/-3.6%, 5.5+/-1.9%, and 7.03+/-2.2%
      elongations (mean+/-S.D.), respectively. We concluded that the collagen fibrils
      underwent significantly greater recruitment (fibril strain relative to global
      tissue strain) at higher strain rates. A better understanding of tendon
      mechanisms at lower hierarchical levels would help establish a basis for future
      development of constitutive models and assist in tissue replacement design.

PMID- 20678773
TI  - Analysis of 70 Environmental Protection Agency priority pharmaceuticals in water
      by EPA Method 1694.
AB  - The U.S. Environmental Protection Agency (EPA) Method 1694 for the determination
      of pharmaceuticals in water recently brought a new challenge for treatment
      utilities, where pharmaceuticals have been reported in the drinking water of 41
      million Americans. This proposed methodology, designed to address this important
      issue, consists of solid-phase extraction (SPE) followed by liquid chromatography
      mass spectrometry (LC/MS-MS) using triple quadrupole. Under the guidelines of
      Method 1694, a multi-residue method was developed, validated, and applied to
      wastewater, surface water and drinking water samples for the analysis of 70
      pharmaceuticals. Four distinct chromatographic gradients and LC conditions were
      used according to the polarity and extraction of the different pharmaceuticals.
      Positive and negative ion electrospray were used with two MRM transitions (a
      quantifier and a qualifier ion for each compound), which adds extra confirmation
      not included in the original Method 1694. Finally, we verify, for the first time,
      EPA Method 1694 on water samples collected in several locations in Colorado,
      where positive identifications for several pharmaceuticals were found. This study
      is a valuable indicator of the potential of LC/MS-MS for routine quantitative
      multi-residue analysis of pharmaceuticals in drinking water and wastewater
      samples and will make monitoring studies much easier to develop for water
      utilities across the US, who are currently seeking guidance on analytical methods
      for pharmaceuticals in their water supplies.

PMID- 20678774
TI  - Application of power functions to chromatographic data for the enhancement of
      signal to noise ratios and separation resolution.
AB  - Chromatographic detection responses are recorded digitally. A peak is represented
      ideally by a Guassian distribution. Raising a Guassian distribution to the power
      'n' increases the height of the peak to that power, but decreases the standard
      deviation by radicaln. Hence there is an increasing disparity in detection
      responses as the signal moves from low level noise, with a corresponding decrease
      in peak width. This increases the S/N ratio and increases peak to peak
      resolution. The ramifications of these factors are that poor resolution in
      complex chromatographic data can be improved, and low signal responses embedded
      at near noise levels can be enhanced. The application of this data treatment
      process is potentially very useful in 2D-HPLC where sample dilution occurs
      between dimension, reducing signal response, and in the application of post
      reaction detection methods, where band broadening is increased by virtue of
      reaction coils. In this work power functions applied to chromatographic data are
      discussed in the context of (a) complex separation problems, (b) 2D-HPLC
      separations, and (c) post-column reaction detectors.

PMID- 20678775
TI  - Covalent immobilization of redox protein via click chemistry and carbodiimide
      reaction: direct electron transfer and biocatalysis.
AB  - In this paper, a simple, facile and general strategy was proposed for the
      covalent biofunctionalization of Au surface with hemoglobin (Hb). Structurally
      well-defined azide-terminated organic self-assembled monolayers (SAMs) were
      formed on Au surface from a mixture solution of azidoundecanethiol and dilute
      thiol. 4-Pentynoic acid was used as a bifunctional linker to immobilized Hb via a
      selective, reliable, robust click reaction and a widely used carbodiimide
      reaction. The surface modification was characterized by reflectance absorption
      infrared (RAIR) spectroscopy, electrochemical impedance spectroscopy (EIS) and
      cyclic voltammetry (CV). The experimental data indicate that the proposed
      methodology is a highly versatile strategy for quantitative, stable and covalent
      attachment of biomacromolecules onto solid interface. The Hb functionalized Au
      electrode shows a pair of well-defined and quasi-reversible peaks at about -0.210
      V (vs. SCE) in 0.1 mol/L pH 5.0 buffers, which stands for the reduction and
      oxidation of Hb Fe(III)/Fe(II) redox couple. The electron transfer rate constant
      (k(s)) was estimated to be 0.78 s(-1). The maximal surface coverage (Gamma) of
      the immobilized Hb was 8.3 x 10(-12) mol cm(-2), indicating the formation of a
      monolayer. Moreover, the biocatalytic activity of the Hb biofunctonalized
      electrode was investigated and an excellent electrocatalytic reduction toward
      O(2) and H(2)O(2) was observed.

PMID- 20678776
TI  - Facile synthesis of core-shell and Janus particles via 2-D dendritic growth of
      gold film.
AB  - We report a facile method for the electroless deposition (ELD) of gold film via
      two-dimensional (2-D) dendritic growth. Our scheme employs protonated amine
      groups, which electrostatically attract both the negatively charged reducing
      agent and gold-precursor. This electrostatic interaction increases the local
      concentrations of gold-precursor and reducing agent near the silica surface to
      levels high enough for gold films with a 2-D fractal morphology to form directly
      on the surfaces of the amine-functionalized silica nanospheres by diffusion
      limited aggregation. Our one-pot reaction avoids the need for seed attachment,
      which is typically employed for the growth of metallic shells on nanospheres.
      Therefore, the proposed method significantly reduces the number of processing
      steps required for the production of core-shell nanospheres. The gold
      morphologies were systematically investigated in terms of various synthesis
      variables, including solution pH, reducing agent concentration, and gold
      precursor injection speed. In addition, we synthesized gold-capped silica
      nanospheres via ELD of gold on a patterned array of silica nanospheres embedded
      in polystyrene (PS) film followed by dissolution of the PS matrix, thus
      demonstrating the potential utility of the proposed method in emerging fields of
      materials science such as patterning of noble metals and studies of nanometer
      scale optics.

PMID- 20678777
TI  - Aggregation of wedge-shaped perylenetetracarboxylic diimides with a different
      number of hydrophobic long alkyl chains.
AB  - Three perylenetetracarboxylic diimide (PDI) derivatives comprising a different
      number of hydrophobic alkoxy chains at one imide nitrogen were synthesized. The
      aggregation behavior of this series of compounds was investigated by UV-vis
      absorption and emission spectra. The results indicated that large number of
      hydrophobic alkyl chains at one end of the PDI molecules can induce significant
      aggregation in solution, but without obvious ground state interaction between the
      PDI aromatic cores. The aggregation behavior of this series of compounds in solid
      state was studied by absorption and IR spectra as well as X-ray diffraction (XRD)
      experiments. The morphology of the solid aggregates was investigated by scanning
      electronic microscopy (SEM). With an increase of the number of alkyl chains at
      one end of these PDI molecules, the aggregation mode varies from H type to J
      type, while the morphology of the solid aggregates changes from small bending
      belts to long ordered wires. This research demonstrated that one can control the
      aggregation mode, the order, and the morphology of the molecular aggregates by
      changing the number of alkyl chains. This information can be useful in the design
      of novel organic materials which exhibit molecular aggregation.

PMID- 20678778
TI  - Using story contexts to bias children's true and false memories.
AB  - The effects of embedding standard Deese/Roediger-McDermott (DRM) lists into
      stories whose context biased interpretation either toward or away from the
      overall themes of the DRM lists on both true and false recognition were
      investigated with 7- and 11-year-olds. These biased story contexts were compared
      with the same children's susceptibility to false memory illusions using the
      standard DRM list presentation paradigm. The results showed the usual age effects
      for true and false memories in the standard DRM list paradigm, where 11-year-olds
      exhibited higher rates of both true and false recognition compared with the 7
      year-olds. Importantly, when DRM lists were embedded in stories, these age
      effects disappeared for true recognition. For false recognition, although
      developmental differences were attenuated, older children were still more
      susceptible to false memory illusions than younger children. These findings are
      discussed in terms of current theories of children's false memories as well as
      the role of themes and elaboration in children's memory development.

PMID- 20678779
TI  - Evolution and long term outcome in patients presenting with large demyelinating
      lesions as their first clinical event.
AB  - OBJECTIVES: To describe the long term evolution and outcome of a homogeneous
      cohort of patients (n=14) with large demyelinating lesions (LDLs) as the first
      clinical event from a group of idiopathic inflammatory demyelinating diseases of
      central nervous system. METHODS: Detailed review of LDLs from December 2002
      January 2007 was made. Patients had at least two magnetic resonance imaging (MRI)
      and minimum follow-up of 2years. The disability was assessed using Estimated
      Expanded Disability Status Scale (EDSS) and Rappaport Disability Rating Scale
      (DRS) at onset and last follow-up. RESULTS: Fourteen consecutive LDL patients
      (male=7), with mean age 32.7years and mean follow-up of 45.5months were included.
      Motor deficits (79%) and cognitive symptoms (43%) marked the onset, none had
      optic neuritis. All except two responded to steroids. Follow-up MRI showed
      complete resolution in 43%, 57% showing marked reduction in size. On follow-up, 2
      relapsed. Mean EDSS and DRS at presentation were 5.93 and 9.07 and at last follow
      up were 1.75 and 2.25 (p<0.001). CONCLUSIONS: Our data suggests that, patients
      presenting with LDLs as their first clinical event behaves distinctly in their
      presentation, imaging characteristics, prognosis and long term outcome as
      compared to MS and ADEM. Albeit significant disability at the onset, these
      patients show an excellent response to treatment with good functional recovery in
      long term and rare relapses.

PMID- 20678780
TI  - Adult-onset leukodystrophy with axonal spheroids.
AB  - We report two cases of adult-onset leukodystrophy with axonal spheroids in a
      brother and sister, one with an autopsy, the other with a cerebral biopsy.
      Symptoms developed at 24 and 33years. The sister died within four years, her
      brother in 2 and a half. Her brain showed a large lesion in the frontal centrum
      semiovale extending through the corpus callosum and shading off into the normal
      appearing U-fibers. With routine stains axonal spheroids were most easily
      detected in the mildly affected regions, although stains for neurofilaments
      showed that they were actually more numerous, though more irregular in shape,
      where the lesions were more severe. Axons and myelin appeared equally affected.
      Pigmented cells were absent. Electron microscopy on the cerebral biopsy showed
      that the spheroids contained neurofilaments and neurotubules, mitochondria and
      degenerate mitochondria, with a suggestion of polarity such that neurofilaments
      were more common in the proximal part of spheroids. Many other axons were found
      whose size was only slightly increased although they were filled with sacs of
      abnormal granular material which were probably derived from mitochondria. The
      anterior commissure and the corticospinal tracts in the spinal cord of the sister
      showed fiber loss and large vacuoles within which occasional intact axons could
      be identified. This was considered to represent intramyelin edema. In the
      cerebral biopsy one vacuole arising from myelin splitting was found in
      confirmation of this hypothesis. We conclude that both myelin and axons are
      damaged, although the lesions of myelin are conditioned by axonal abnormalies in
      this genetic disease.

PMID- 20678781
TI  - Relationships between volatile and non-volatile metabolites and attributes of
      processed potato flavour.
AB  - Although the flavour of processed potatoes (Solanum tuberosum L.) is important to
      consumers, the blend of volatile and non-volatile metabolites that impact on
      flavour attributes is not well-defined. Additionally, it is important to
      understand how potato flavour changes during storage. In this study, quantitative
      descriptive analysis of potato samples by a trained taste panel was undertaken,
      comparing tubers from S. tuberosum group Phureja with those from S. tuberosum
      group Tuberosum, both at harvest and following storage. The cooked tuber volatile
      profile was analysed by solid phase micro extraction followed by gas
      chromatography-mass spectrometry analysis in sub-samples of the tubers that were
      assessed by taste panels. A range of non-volatile metabolites including the major
      umami compounds, glycoalkaloids and sugars was also measured in tuber sub
      samples. Correlation and principal component analyses revealed differences
      between the potato cultivars and storage conditions and demonstrated associations
      of metabolites with the different sensory attributes.

PMID- 20678782
TI  - Immunofluorescence localization of levopimaradiene/abietadiene synthase in methyl
      jasmonate treated stems of Sitka spruce (Picea sitchensis) shows activation of
      diterpenoid biosynthesis in cortical and developing traumatic resin ducts.
AB  - Conifers produce terpenoid-rich oleoresin in specialized resin ducts as a main
      line of defence against pests and pathogens. In spruce species (Picea spp.),
      axial resin ducts are either present constitutively in the cortex tissue
      (cortical resin ducts, CRDs) or are formed de novo as traumatic resin ducts
      (TRDs) in the cambial zone upon attack by insects, fungi or treatment with methyl
      jasmonate (MeJA). Using immunofluorescence localization we tested if previously
      formed CRDs respond to MeJA treatment with increased capacity for diterpenoid
      biosynthesis. We also tested the dynamics of diterpene synthase localization in
      the cambial zone. Immunofluorescence localization was performed using an antibody
      against a diterpene synthase, levopimaradiene/abietadiene synthase (LAS), in stem
      cross-sections of untreated and 0.1% MeJA-treated 4-year old Sitka spruce (P.
      sitchensis) trees. No fluorescence signal was observed in untreated stem cross
      sections; however, signal was present 2 days after treatment with MeJA
      exclusively in the epithelial cells of CRDs. Fluorescence steadily increased in
      the CRD epithelial cells 4 and 8 days after treatment. At 8days, additional
      fluorescence was observed in developing epithelial cells of traumatic resin ducts
      TRDs in the cambial zone. These results confirm that resin duct epithelial cells
      are the main site of diterpene biosynthesis in Sitka spruce, diterpenoid
      biosynthesis is induced in CRD epithelial cells early upon treatment with MeJA,
      and immature developing TRD epithelial cells produce diterpene synthase enzyme.
      Overall, the results of this work improve our understanding of spatial and
      temporal patterns of induced diterpene resin acid biosynthesis in conifers.

PMID- 20678783
TI  - Cytotoxic cassaine diterpenoid-diterpenoid amide dimers and diterpenoid amides
      from the leaves of Erythrophleum fordii.
AB  - Detailed phytochemical investigation from the leaves of Erythrophleum fordii
      resulted in the isolation of 13 compounds, including three cassaine diterpenoid
      diterpenoid amide dimers (1, 3 and 5), and seven cassaine diterpenoid amides (6
      and 8-13), together with three previously reported ones, erythrophlesins D (2), C
      (4) and 3beta-hydroxynorerythrosuamide (7). Compounds 1, 3 and 5 are further
      additions to the small group of cassaine diterpenoid dimers represented by
      erythrophlesins A-D. Their structures were determined by analysis of extensive
      one- and two-dimensional NMR experiments and ESIMS methods. Cytotoxic activities
      of the isolated compounds were tested against HCT-8, Bel-7402, BGC-823, A549 and
      A2780 human cancer cell lines in the MTT test. Results showed that compounds 1
      and 3-5 exhibited significantly selective cytotoxic activities (IC(50)<10 microM)
      against these cells, respectively.

PMID- 20678784
TI  - Pulmonary function measurements immediately after exercise are correlated with
      neutrophil percentage in tracheal aspirates in horses with poor racing
      performance.
AB  - Inflammatory airway disease (IAD) is common in racehorses, and is a cause of
      wastage in the industry. IAD has been diagnosed by measurement of percent
      neutrophils (N%) in tracheal aspirates (TA). The aim of this study was to
      investigate whether spirometric indices of pulmonary function were correlated
      with N% in TAs. Limits to breathing were measured by analyses of relationships
      between relative times and relative respiratory gas flows during inspiration and
      expiration in individual breaths recorded after exercise. Horses with higher N%
      had significantly lower relative gas flows at the same relative times during
      inspiration and expiration, suggesting a limit to breathing. These findings
      confirm a physiological basis for the measurement of N% in TA after exercise for
      diagnosis of IAD. Spirometric pulmonary function testing using analyses of
      individual breaths after exercise has application for assessment of pulmonary
      function and poor exercise performance.

PMID- 20678785
TI  - Pathological effects of Cryptostegia venusta toxicity in goats and rats.
AB  - Here, we aimed to determine the toxicity of Cryptostegia venusta in goats and
      rats. We orally administered a single 60 g dose of shredded C. venusta leaves per
      kilogram of body weight to three goats. The animals were necropsied after death,
      and tissue sections were collected and routinely processed for histopathological
      analyses. Additionally, we separated 25 adult male Wistar rats (each weighing
      about 150 g) into five groups: an untreated control group and groups orally
      treated with 1, 3, 10, or 60 g/kg doses. Rats were sacrificed 72 h after
      administration of the C. venusta extract, and tissue sections collected for
      histopathological analyses. All goats presented signs of apathy, salivation,
      frequent urination, and eventually fatigue 4-6h after receiving C. venusta. Two
      goats died 20 h after administration, and the third was sacrificed in extremis.
      The only histopathological finding observed in the goats was lung edema. No rats
      died during the experimental period or presented any clinical signs or
      macroscopic lesions. However, both goats and rats exhibited degeneration and
      multifocal necrosis of cardiac muscle fibers. From our results, we conclude that
      the C. venusta plant is capable of promoting cardiotoxicity.

PMID- 20678786
TI  - A comprehensive microbial insight into two-stage anaerobic digestion of food
      waste-recycling wastewater.
AB  - Microbial community structures were assessed in a two-stage anaerobic digestion
      system treating food waste-recycling wastewater. The reactors were operated for
      390 d at 10 different hydraulic retention times (HRTs) ranging from 25 to 4 d.
      Stable operation was achieved with the overall chemical oxygen demand (COD)
      removal efficiency of 73.0-85.9% at organic loading rate of up to 35.6 g COD/L.d.
      Performance of the acidogenic reactors, however, changed significantly during
      operation. This change coincided with transition of the bacterial community from
      one dominated by Aeriscardovia- and Lactobacillus amylovorus-related species to
      one dominated by Lactobacillus acetotolerans- and Lactobacillus kefiri-like
      organisms. In methanogenic reactors, the microbial community structures also
      changed at this stage along with the shift from Methanoculleus- to Methanosarcina
      like organisms. This trend was confirmed by the non-metric multidimensional
      scaling joint plot of microbial shifts along with performance parameters. These
      results indicated that the overall process performance was relatively stable
      compared to the dynamic changes in the microbial structures and the acidogenic
      performance.

PMID- 20678787
TI  - Assessment of plausible bioindicators for plant performance in advanced
      wastewater treatment systems.
AB  - Three full-scale advanced biological systems for nitrogen removal showing
      different efficiencies were assessed during one year, to investigate the protist
      communities supported in these wastewater treatment plants (WWTP). The main goal
      of this research was to explore the differences of these communities from those
      observed in conventional activated sludge systems. The final objective was to
      provide background support for the proposal of bioindicators in this type of
      biological systems, where scarce information was available until now, since only
      conventional systems had been previously studied from this point of view. Results
      obtained indicate that, in fact, protist population density and diversity in
      advanced systems for N-elimination are quite different from other wastewater
      systems studied before. A statistical approach through multivariate analysis was
      developed to search for association between protist species and physical-chemical
      system performance, and specifically N-removal efficiencies. The original
      hypothesis proposing that previous indicators from conventional systems are not
      adequate in advanced N-removal mechanisms was proved to be correct. Efficient
      processes on N-removal, despite what it had been usually found in conventional
      systems, show important flagellate and amoeba populations and these populations
      tend to reduce their abundances as nitrogen removal performance decreases
      (moderate to low). Ciliates are however less abundant in these N-removal
      efficient systems. Certain groups and genera of protist such as flagellates and
      small amoebae are thus proposed as indicative of high performance N-removal,
      while in this case the appearance of certain ciliates were indicative of low
      performance on N- or high organic matter removal (as COD) efficiencies.

PMID- 20678788
TI  - The importance of sediment and submerged aquatic vegetation as potential habitats
      for persistent strains of enterococci in a subtropical watershed.
AB  - Recent evidence of extended survival of fecal indicator bacteria in sediments and
      submerged aquatic vegetation (SAV) has raised concerns about using indicator
      bacteria to reliably detect fecal contamination. We monitored enterococci
      densities and population structure in water, sediment and SAV simultaneously at
      sites across a subtropical watershed (Tampa Bay, FL, USA) over one year to
      determine the extent to which each matrix serves as a potential reservoir of
      enterococci. SAV harbored significantly higher mean densities of enterococci than
      sediments, which harbored higher densities than water. Mean enterococci densities
      were also greater at sites located further upstream in the watershed. The
      population structure assessed by BOX-PCR genotyping was relatively dissimilar in
      each sample, although some similarities among samples suggested grouping by
      location. Strain diversity ranged from very high to negligible, with lowest
      overall diversity in lake samples taken during the summer. Several strains were
      highly abundant and cosmopolitan (found across sites, seasons, and matrices) and
      were identified by 16S rRNA gene sequencing as the Enterococcus species
      casseliflavus, faecalis, faecium, hirae, and mundtii. The proportional dominance
      of certain strains suggests the existence of persistent and possibly naturalized
      indicator bacteria populations that are not directly related to pollution events.

PMID- 20678789
TI  - Transport of metal oxide nanoparticles in saturated porous media.
AB  - The behavior of four types of untreated metal oxide nanoparticles in saturated
      porous media was studied. The transport of Fe(3)O(4), TiO(2), CuO, and ZnO was
      measured in a series of column experiments. Vertical columns were packed with
      uniform, spherical glass beads. The particles were introduced as a pulse
      suspended in aqueous solutions and breakthrough curves at the outlet were
      measured using UV-vis spectrometry. Different factors affecting the mobility of
      the nanoparticles such as ionic strength, addition of organic matter (humic
      acid), flow rate and pH were investigated. The experiments showed that mobility
      varies strongly among the nanoparticles, with TiO(2) demonstrating the highest
      mobility. The mobility is also strongly affected by the experimental conditions.
      Increasing the ionic strength enhances the deposition of the nanoparticles. On
      the other hand, addition of humic acid increases the nanoparticle mobility
      significantly. Lower flow rates again led to reduced mobility, while changes in
      pH had little effect. Overall, in natural systems, it is expected that the
      presence of humic acid in soil and aquifer materials, and the ionic strength of
      the resident water, will be key factors determining nanoparticle mobility.

PMID- 20678790
TI  - Comparison of biological and chemical measures of metal bioavailability in field
      soils: test of a novel simulated earthworm gut extraction.
AB  - Bioavailability of metals in soil is a major factor influencing estimates of risk
      associated with exposure of ecological receptors. Metal concentrations in soil
      are often compared to ecological screening benchmarks, which are based on total
      concentrations in soil. Often, the total concentration is not correlated with
      toxicity. No standardised method exists for determining the bioavailability of
      metals in soil to ecological receptors. Several surrogate measures of
      bioavailability were compared to the results of a battery of toxicity tests using
      copper (Cu), lead (Pb), and zinc (Zn)-contaminated soils collected from a former
      industrial area. A calcium chloride (CaCl(2)) extraction, cyclodextrin (HPCD)
      extraction, simulated earthworm gut (SEG) test, and earthworm bioaccumulation
      test were performed using the soils. Extractable metals using the CaCl(2)
      solution were not correlated with any biological responses of earthworms (Eisenia
      andrei), collembola (Folsomia candida), northern wheatgrass (Elymus lanceolatus),
      or alfalfa (Medicago sativa L.). Concentrations of metals in the HPCD extracts
      were highly variable and were not adequate for revealing adverse effects. E.
      andrei tissue concentrations were variable but were predictive of adverse effects
      to invertebrates. The results of the SEG test correlated with most of the
      biological endpoints. Bioavailable Cu was correlated with adverse effects to
      invertebrates and plants using the SEG test. Overall, coefficients of
      determination associated with the relationships between the biological responses
      and each measure of bioavailability indicated that those for the SEG test were
      greater than those for the other surrogate measures of bioavailability. Further
      validation is required before this test is routinely used to estimate metal
      bioavailability and toxicity.

PMID- 20678791
TI  - Modulation of N400 in chronic non-fluent aphasia using low frequency Repetitive
      Transcranial Magnetic Stimulation (rTMS).
AB  - Low frequency Repetitive Transcranial Magnetic Stimulation (rTMS) has previously
      been applied to language homologues in non-fluent populations of persons with
      aphasia yielding significant improvements in behavioral language function up to
      43 months post stimulation. The present study aimed to investigate the
      electrophysiological correlates associated with the application of rTMS through
      measurement of the semantic based N400 Event-related brain potentials (ERP)
      component. Low frequency (1 Hz) rTMS was applied to the anterior portion of the
      homologue to Broca's area (pars triangularis), for 20 min per day for 10 days,
      using a stereotactic neuronavigational system. Twelve non-fluent persons with
      aphasia, 2-6 years post stroke were stimulated. Six participants were randomly
      assigned to receive real stimulation and six participants were randomly assigned
      to receive a blind sham control condition. ERP measures were recorded at
      baseline, 1 week and 2 months subsequent to stimulation. The findings demonstrate
      treatment related changes observed in the stimulation group when compared to the
      placebo control group at 2 months post stimulation indicating neuromodulation of
      N400 as a result of rTMS. No treatment related changes were identified in the
      stimulation group, when compared to the sham group from baseline to 1 week post
      stimulation. The electrophysiological results represent the capacity of rTMS to
      modulate neural language networks and measures of lexical-semantic function in
      participants with non-fluent aphasia and suggest that time may be an important
      factor in brain reorganization subsequent to rTMS.

PMID- 20678792
TI  - Perfusion and characterization of an endothelial cell-seeded modular tissue
      engineered construct formed in a microfluidic remodeling chamber.
AB  - Tissue engineered constructs containing tortuous endothelial cell-lined perfusion
      channels were formed by randomly assembling endothelial cell-seeded submillimeter
      sized collagen cylinders (modules) into a microfluidic perfusion chamber. The
      interconnected void space produced by random module packing created flow channels
      that were lined with endothelial cells. The effect of perfusion (0.5 mL min(-1),
      Re( *) = 27.78 and shear stress = 0.16 dyn cm(-2)) through the tortuous channels
      on construct remodeling and endothelium quiescence was studied. Over time,
      modules fused at their points of contact and as they contracted, decreased the
      internal void space, which reduced the overall perfusion through the construct.
      As compared to static controls, perfusion caused a transient increase in
      activation (ICAM-1 and VCAM-1 expression) after 1 h followed by a decrease after
      24 h. Proliferation (by BrdU) was reduced significantly, while KLF2, which is
      upregulated with atheroprotective laminar shear stress, was upregulated
      significantly after 24 h. VE-cadherin became discontinuous and was significantly
      downregulated after 24 h, which was likely caused by the dismantling of the
      endothelial cell adherens junctions during remodeling. Collectively, these
      outcomes suggest that flow through the construct did not drive the endothelial
      cells towards an inflamed, "atherosclerotic like" disturbed flow pathology.

PMID- 20678793
TI  - ASIC1a channels are activated by endogenous protons during ischemia and
      contribute to synergistic potentiation of intracellular Ca(2+) overload during
      ischemia and acidosis.
AB  - Acidosis accompanying cerebral ischemia activates acid-sensing ion channels
      (ASIC) causing increases in intracellular calcium concentration ([Ca(2+)]i) and
      enhanced neuronal death. Experiments were undertaken in rat cortical neurons to
      explore the effects of ASIC1a activation on ischemia-induced [Ca(2+)]i elevations
      and whole-cell currents. There was a significant contribution of ASIC1a channels
      to ischemia-evoked [Ca(2+)]i increases at pH 7.4, suggesting that ASIC1a channels
      are activated by endogenous protons during ischemia. The combination of ischemia
      and acidosis resulted in synergistic increases in [Ca(2+)]i and plasma membrane
      currents relative to acidosis or ischemia alone. ASIC1a inhibitors significantly
      blunted [Ca(2+)]i increases and a transient current activated by
      ischemia+acidosis, demonstrating that homomeric ASIC1a channels are involved.
      However, ASIC1a inhibitors failed to diminish a sustained current activated in
      response to combined ischemia and acidosis, indicating that acidosis can
      potentiate ischemia effects through mechanisms other than ASIC1a. The [Ca(2+)]i
      overload produced by acidosis and ischemia was not blocked by tetrodotoxin, 2
      amino-5-phosphonopentanoic acid or nifedipine. Thus, acidosis and activation of
      ASIC1a channels during ischemia can promote [Ca(2+)]i overload in the absence of
      neurotransmission, independent of NMDA receptor or L-type voltage-gated Ca(2+)
      channel activation. Postsynaptic ASIC1a channels play a critical role in ischemia
      induced [Ca(2+)]i dysregulation and membrane dysfunction.

PMID- 20678794
TI  - Zinc tolerance and accumulation in the ferns Polypodium cambricum L. and Pteris
      vittata L.
AB  - Zn uptake and compartmentalisation were studied in two ferns, the European
      Polypodium cambricum L., a possible Zn tolerant, and the sub-tropical Pteris
      vittata L., an As accumulator also able to accumulate Zn. Ferns growing in
      hydroponic systems were exposed to Zn concentrations ranging from non-toxic to
      lethal doses (0, 50, 125, 250, 500 mg kg(-1) as ZnSO4). After treatments, the
      following analyses were made: photosynthetic efficiency (Handy PEA), anatomical
      symptoms (optical and scanning electron microscopy), determination of Zn in
      fronds, rhizome and roots (atomic emission spectrometry, ICP-AES). Both species
      showed high bioconcentration and bioaccumulation factors, but low translocation
      factor, indicating Zn sequestration in the root/rhizome system. P. cambricum was
      more resistant to Zn, while P. vittata suffered from unrestricted uptake leading
      to macro- and microscopical damages and plant death. Data suggest that P.
      cambricum could be suitable for phytostabilisation of Zn-contaminated soils in
      temperate areas.

PMID- 20678795
TI  - Isolates of Comamonas spp. exhibiting catalase and peroxidase activities and
      diversity of their responses to oxidative stress.
AB  - For survival isolates of Comamonas testosteroni CCM 1931, C. testosteroni K3, C.
      terrigena N3H or N1C and C. terrigena CCM 2409, selected largely from polluted
      environments, the production of catalase and dianisidine-peroxidase activity was
      important. Electrophoretic resolution of cell-free extracts of aerobically grown
      strains in Luria-Bertani medium during the exponential phase revealed distinctive
      expression of catalatic and peroxidatic activities detected with 3,3'
      diaminobenzidine tetrahydrochloride (DAB). The protection of isolates from 20 or
      40 mM H(2)O(2) stress was characterized with a considerable diversity in catalase
      and peroxidase responses that resulted from hydroperoxidase's variant of original
      isolates, indicating also a selective pressure of environment. Results indicate
      catalase to be important for adaptation of cultures to high concentration of 60mM
      H(2)O(2). The greatest appreciable differences in sensitivity to toxic effect of
      H(2)O(2) (20 or 40 mM) treatment between individual isolates and their adapted
      variants during the growth were observed until the middle of exponential phase.
      Isolates exhibited diversity in catalases responses to possible contaminants o-or
      p-phenylenediamine (PDA) as well. Only positional isomer p-PDA (1 or 2mM)
      stimulated catalase activity unlike from isomer o-PDA in C. terrigena N3H cells.
      The study can contribute to understanding of bacterial antioxidative enzymatic
      responses in the presence of possible physiological stress resulting mainly from
      environmental pollutants.

PMID- 20678796
TI  - In vivo genotoxicity and stress defences in three flatfish species exposed to
      CuSO4.
AB  - We have used the comet assay to analyse, after 3h, 24h and 6 days, the genotoxic
      effect in vivo of applying a single intraperitoneal injection of CuSO4, at a
      concentration of 2mg/kg, to adult specimens of Solea senegalensis, Dicologlossa
      cuneata and Scophthalmus rhombus. Metals content (Cu, Zn and Cd) in liver was
      also measured. The activity of key stress defences was evaluated by analysing
      antioxidant enzyme activity (catalase (CAT), superoxide dismutase (SOD), total
      glutathione peroxidase (t-GPX), glutathione reductase (GR), glucose-6-phosphate
      dehydrogenase (G6PDH) and 6-phosphogluconate dehydrogenase (6PGDH)),
      metallothionein (MT) and heat shock proteins (HSP70 and HSP60). The results show
      that CuSO4 intake generates high and cumulative levels of genotoxicity throughout
      the 6 days in all 3 species. After 6 days, metals content detected in specimens
      showed significant differences from controls. Inter-species differences were
      detected in enzyme activity (P<0.05). A clear response to CuSO4 was detected only
      in S. rhombus, with an increase of MT and a decrease of HSPs. Variations in
      antioxidant defence levels and their comparative responses to the stress-inducing
      agent are discussed.

PMID- 20678797
TI  - Urinary heavy metal levels and relevant factors among people exposed to e-waste
      dismantling.
AB  - Primitive electronic waste (e-waste) recycling has become a growing environmental
      concern, and toxic heavy metals released from e-waste activities may continue to
      threaten the health of local people. To study the impact of heavy metals in
      people around e-waste sites, 349 people from e-waste recycling sites (exposure
      group) and 118 people from a green plantation (control group) were surveyed, and
      their urinary levels of lead (UPb), cadmium (UCd), manganese (UMn), copper (UCu),
      and Zinc (UZn) were assayed. Questionnaire surveys for risk factors were also
      performed and analyzed by using the Pearson correlation analysis. Results
      indicated that the levels of urinary Cd in both occupational dismantling people
      {GM(GSD) 0.72(0.71) ug/L} and non-occupational dismantling people {GM(GSD)
      0.50(0.79) ug/L} were higher than the control group {GM(GSD) 0.27(0.85) ug/L}.
      Further analyses of correlations between urinary heavy metal levels and exposure
      factors in the exposed group revealed positive relationship between the duration
      of dismantling and the level of UPb (p < 0.05). Meanwhile, rice sources from
      local village have a positive correlation with the level of UPb and UCd (p <
      0.01). Other factors, however, may also have influences on heavy metal burden,
      and not all urinary heavy metal levels can be contributed to e-waste dismantling
      exposure levels. Primitive e-waste recycling activities may contribute to the
      changes of urinary heavy metal levels and increase the health risk for those
      chronically working on e-waste dismantling.

PMID- 20678798
TI  - Mast cells: emerging sentinel innate immune cells with diverse role in immunity.
AB  - Mast cells are phylogenetically old innate immune cells with less recognition in
      normal function of immune system as no such disease has been observed in humans
      due to their deficiency or inadequate function. Earlier mast cells were only
      known for their important role in the type 1 allergic reactions (i.e. anaphylaxis
      or some contact hypersensitivity reactions) due to release of various biochemical
      mediators (i.e. cytokines, chemokines, lipid mediators, proteases and biologic
      amines). Several studies indicated that they do not only come in action upon
      binding of IgE to its corresponding receptors expressed by them but also play an
      important role in host immunity. Recent development in understanding the mast
      cell biology has established various important roles of these cells in regulating
      both innate as well as adaptive immune response under normal or
      pathophysiological conditions (i.e. acute or chronic bacterial or parasitic
      infections, various autoimmune disease, pregnancy, etc.). Present review is
      designed to accommodate up to date information regarding mast cell development
      (i.e. factors governing mast cell development and their homing to various
      compartments (i.e. skin, lungs, intestine, uterus, etc.) along with their role in
      innate immunity, human pregnancy and future immunomodulatory approach comprising
      of targeting mast cells.

PMID- 20678799
TI  - Ranibizumab for choroidal neovascularization secondary to causes other than age
      related macular degeneration: a phase I clinical trial.
AB  - PURPOSE: To investigate the safety and efficacy of ranibizumab for the treatment
      of choroidal neovascularization (CNV) secondary to causes other than age-related
      macular degeneration (AMD). DESIGN: Multicenter, randomized, 12-month clinical
      trial. PARTICIPANTS: Thirty patients with CNV due to causes other than AMD,
      including pathologic myopia, ocular histoplasmosis, and angioid streaks. METHODS:
      Participants were randomly assigned 1:1 to monthly intravitreal injections of 0.5
      mg ranibizumab or 3 monthly injections followed by dosing as needed (pro re nata
      [PRN]) at monthly follow-up visits. MAIN OUTCOME MEASURES: Outcome measures
      included the incidence of ocular and nonocular adverse events, the percentage of
      patients gaining >= 15 letters of visual acuity (VA) at 6 and 12 months from
      baseline, the percentage of patients losing >= 15 letters of VA at 6 and 12
      months from baseline, and mean change in VA and central retinal thickness (CRT)
      at 6 and 12 months from baseline. RESULTS: No serious ocular or systemic adverse
      events related to ranibizumab or the injection procedure were reported. Among
      patients who received monthly ranibizumab injections, 8 of 12 (66.7%) gained >=
      15 letters of VA at both 6 and 12 months, and among patients who received PRN
      injections, 9 of 14 (64.3%) and 8 of 14 (57.1%) gained >= 15 letters of VA at 6
      and 12 months, respectively. No patient in the study lost >= 15 letters of VA.
      Mean VA improved significantly from baseline by 23.9 +/- 5.4 (P = 0.001) and 21.1
      +/- 4.3 letters (P = 0.0003) at 6 months and by 26.9 +/- 5.3 (P = 0.0003) and
      19.2 +/- 3.8 letters (P = 0.0002) at 12 months in the monthly and PRN treatment
      arms, respectively. Mean CRT decreased significantly from baseline by 103.4 +/-
      18.9 (P = 0.0005) and 161.1 +/- 43.7 MUm (P = 0.0034) at 6 months and by 109.3 +/
      19.5 (P = 0.0004) and 166.6 +/- 38.4 MUm (P = 0.001) at 12 months in the monthly
      and PRN treatment groups, respectively. No statistically significant difference
      was found between treatment groups in change in VA or CRT at any time point.
      CONCLUSIONS: Intravitreal ranibizumab, given as monthly injections or as 3
      monthly injections followed by PRN dosing, showed a promising efficacy and safety
      profile in the treatment of CNV due to causes other than AMD.

PMID- 20678800
TI  - Stromal support for Descemet's membrane endothelial keratoplasty.
AB  - PURPOSE: To evaluate the use of a peripheral stromal support to facilitate and
      improve the outcomes of Descemet's membrane endothelial keratoplasty (DMEK).
      DESIGN: Prospective case series. PARTICIPANTS: Ten patients with Fuchs'
      endothelial dystrophy. INTERVENTION: Pneumatic dissection was used to detach the
      central part of the Descemet's membrane and endothelium from the deep stroma.
      Endothelial grafts including a peripheral stromal support were obtained by
      eccentric punching of donor tissue and used to perform DMEK surgery in 10
      patients. MAIN OUTCOME MEASURES: Operative time, graft attachment rate, best
      spectacle-corrected visual acuity (BSCVA), endothelial cell loss, refraction, and
      complications. RESULTS: In all cases the surgical time was <= 1 hour. The
      postoperative course was uneventful in all but 2 cases, which required rebubbling
      owing to early graft detachment. Final attachment rate was 100%. The average
      follow-up was 8.4 months (range, 6-12). Postoperative BSCVA was >= 20/40 in all
      cases and no substantial change in refraction was recorded. Postoperative
      endothelial cell loss averaged 24.1% (range, 8%-34.9%). CONCLUSIONS: Stromal
      support facilitates surgery, reduces complications, and appears to maintain the
      favorable outcomes of DMEK.

PMID- 20678801
TI  - Intraocular and systemic pharmacokinetics of triamcinolone acetonide after a
      single 40-mg posterior subtenon application.
AB  - PURPOSE: To characterize the pharmacokinetics of triamcinolone acetonide (TA) in
      aqueous, vitreous, and systemic circulation after a single subtenon injection.
      DESIGN: Prospective interventional case series. PARTICIPANTS: Thirty-six patients
      (36 eyes) who received a single posterior subtenon injection of TA (40 mg in 0.4
      ml). METHODS: Aqueous, vitreous, and blood samples were obtained at 1-hour, 1
      day, 3-day, 5-day, 10-day, 14-day, 21-day, and 28-day time points after the
      posterior subtenon TA injection. At each time point, there were 3 to 6 eyes
      (patients). The concentrations of TA in the aqueous, vitreous, and plasma were
      analyzed using ultra-performance liquid chromatography coupled with tandem mass
      spectrometry. MAIN OUTCOME MEASURES: Triamcinolone acetonide concentration in the
      samples was measured, and pharmacokinetic parameters were calculated. RESULTS:
      The TA concentration-time profile in aqueous consisted of a fast distribution
      phase during the first 24 hours and a slow elimination phase thereafter. In
      contrast, the TA concentration-time profile in vitreous consisted of an
      absorption phase during the first 24 hours followed by a slow elimination phase.
      The TA in plasma followed a mono-exponential elimination during the study course.
      The TA concentration peak time for aqueous and plasma was at 1 hour and 24 hours,
      for vitreous after subtenon injection. The terminal elimination half-life in
      aqueous, vitreous, and plasma was 11.8, 17.1, and 25 days, respectively. The
      integral of the area under the concentration time curve (AUC(0-infinity)) was 862
      ng/day/ml for aqueous, 1262 ng/day/ml for vitreous, and 17.4 ng/day/ml for
      plasma. The total TA exposure to vitreous was 46% more than total TA exposure to
      the aqueous. The TA concentration in vitreous was 70- to 98-fold higher than that
      in plasma. CONCLUSIONS: Posterior subtenon TA application can provide a sustained
      high local ocular TA level while also resulting in a very low systemic TA level,
      which may be well below the normal glucocorticoid level in humans.

PMID- 20678802
TI  - Retinal nerve fiber layer imaging with spectral-domain optical coherence
      tomography: pattern of RNFL defects in glaucoma.
AB  - OBJECTIVE: To characterize the distribution pattern, angular width, and area of
      retinal nerve fiber layer (RNFL) defects in glaucoma using spectral-domain
      optical coherence tomography (OCT). DESIGN: Prospective, cross-sectional study.
      PARTICIPANTS: We included 113 normal subjects and 116 glaucoma patients. METHODS:
      One eye from each individual was randomly selected for Cirrus HD-OCT (Carl Zeiss
      Meditec Inc., Dublin, CA) RNFL imaging of the 6 * 6-mm2 parapapillary region. The
      RNFL defects were identified in the RNFL thickness deviation map as superpixels
      coded in red. The angular location and the angular width of RNFL defects were
      measured. The proportion of area with RNFL measurements within the normal ranges
      in the RNFL thickness deviation map was expressed as the RNFL area index (RAI): 1
      - [area of superpixels coded in red/(6 * 6 - optic disc and parapapillary
      atrophic area)]. The diagnostic performance between RAI and average RNFL
      thickness was compared with the area under the receiver operating characteristic
      curve after adjusting refraction, signal strength, optic disc, and parapapillary
      atrophic areas. MAIN OUTCOME MEASURES: Frequency distribution profiles and
      distribution patterns of RNFL defects, diagnostic sensitivity and specificity of
      RAI, and average RNFL thickness. RESULTS: The RNFL defects in glaucoma were most
      frequently found at the inferotemporal meridian at 284 degrees  (80.4%), followed
      by the superotemporal meridians at 73 degrees  (54.2%). The respective
      proportions of localized (angular width <= 30 degrees ) and diffuse (angular
      width > 30 degrees ) RNFL defects were 11.4% and 70.5% in mild glaucoma (MD >= 6
      dB), and 4.2% and 94.5% in moderate to advanced glaucoma (MD < -6 dB). The RAI
      was 90.2 +/- 6.4% and 83.6 +/- 7.4% in the mild and moderate to advanced glaucoma
      groups, respectively. At a specificity of 90.0%, the respective diagnostic
      sensitivity of RAI and average RNFL thickness was 95.7% (95% confidence interval,
      92.2-99.1%) and 94.0% (90.1-99.1%). CONCLUSIONS: Analysis of the pattern of RNFL
      defects with spectral domain OCT imaging offers important insights in
      understanding the characteristics of RNFL damage. As RNFL defects expand in size
      as the disease progresses, measurement of the angular width and area of RNFL
      defects can provide an additional dimension for evaluation of glaucoma.

PMID- 20678803
TI  - Complement factor H and high-temperature requirement A-1 genotypes and treatment
      response of age-related macular degeneration.
AB  - PURPOSE: To determine whether there is an association between complement factor H
      (CFH), high-temperature requirement A-1 (HTRA1), vascular endothelial growth
      factor (VEGF), and pigment epithelium-derived factor (PEDF) genotypes and
      response to treatment with photodynamic therapy (PDT) for age-related macular
      degeneration (AMD) in a Japanese population. DESIGN: Prospective, case-control
      study. PARTICIPANTS: One hundred ten patients with exudative AMD treated by
      verteporfin PDT were recruited prospectively at the Department of Ophthalmology,
      Saitama Medical University Hospital, Saitama, Japan. METHODS: The patients were
      genotyped for 4 single nucleotide polymorphisms (SNPs; rs800292, rs1061170,
      rs1410996, rs2274700) in the CFH gene, a rs11200638-SNP in the HTRA1 gene, 3 SNPs
      (rs699947, rs1570360, rs2010963) in the VEGF gene, and 4 SNPs (rs12150053,
      rs12948385, rs9913583, rs1136287) in the PEDF gene using a TaqMan assay. MAIN
      OUTCOME MEASURES: The treatment outcomes and genotypes of CFH, HTRA1, VEGF, and
      PEDF polymorphisms. RESULTS: Best-corrected visual acuity 1 year after PDT was
      significantly increased in patients with the HTRA1-rs11200638 GG genotype as
      compared with patients with the GA or AA genotypes (P = 2.9 * 10-2, 7.0 * 10-4,
      respectively). The rate of recurrence in the 12-month period after PDT was also
      associated with HTRA1-rs11200638 genotype (P = 3.12 * 10-2). Patients with the AA
      genotype of HTRA1-rs11200638 had an approximately 6-fold greater risk of the
      recurrence than patients with the GG genotype (P = 5.58 * 10-3). Significant
      differences were demonstrated in the mean time interval from the initial
      treatment to the time of recurrence for the genotypes of CFH-rs1410996/-rs2274700
      (P = 8.50 * 10-3). CONCLUSIONS: The HTRA1-rs11200638 and CFH-rs1410996/-rs2274700
      variants were associated with response to PDT in this study population. These
      variants may be used for genetic biomarkers to estimate visual outcomes and
      recurrences in the response to PDT with significant predictive power.

PMID- 20678804
TI  - Perifoveal muller cell depletion in a case of macular telangiectasia type 2.
AB  - PURPOSE: To assess the histopathologic changes in a postmortem sample derived
      from an eye donor with macular telangiectasia (MacTel) type 2 to gain further
      insight into the cause of the disease. DESIGN: Clinicopathological case report.
      PARTICIPANTS: Postmortem tissue was collected from 5 different donors: 1 MacTel
      type 2 patient; 1 healthy control; 2 type 2 diabetic patients, 1 with retinopathy
      and 1 without retinopathy; and 1 patient with unilateral Coat's disease. METHODS:
      Macular pigment distribution in the posterior part of freshly dissected eyes was
      documented by macrophotography. Paraffin sections from both the macular and
      peripheral regions were assessed using antigen retrieval and immunohistochemistry
      to study the distribution of cell-specific markers. Blood vessels were visualized
      with antibodies directed against collagen IV and claudin 5; glial cells with
      antibodies against glial fibrillary acidic protein (GFAP), vimentin, glutamine
      synthetase (GS), and retinaldehyde binding protein (RLBP1, also known as CRALBP);
      microglia with an antibody against allograft inflammatory factor 1 (also known as
      Iba1); and photoreceptors with antibodies against rhodopsin and opsin. Using
      anatomic landmarks, the sections then were matched with the macular pigment
      distribution and a fluorescein angiogram of the patient that was obtained before
      the patient's death. MAIN OUTCOME MEASURES: Presence and distribution of macular
      pigment and cell-specific markers. RESULTS: Macular pigment was absent in the
      macula. Furthermore, abnormally dilated capillaries were identified in a macular
      region that correlated spatially with regions of fluorescein leakage in an
      angiogram that was obtained 12 years before death. These telangiectatic vessels
      displayed a marked reduction of the basement membrane component collagen IV,
      indicating vascular pathologic features. The presence of GFAP was limited to
      retinal astrocytes, and no reactive Muller cells were identified. Importantly,
      reduced immunoreactivity with Muller cell markers (vimentin, GS, and RLBP1) in
      the macula was observed. The area that lacked Muller cells corresponded with the
      region of depleted macular pigment. CONCLUSIONS: These findings suggest that
      macular Muller cell loss or dysfunction is a critical component of MacTel type 2,
      which may have implications for future treatment strategies.

PMID- 20678805
TI  - Effects of vitreomacular adhesion on anti-vascular endothelial growth factor
      treatment for exudative age-related macular degeneration.
AB  - OBJECTIVE: To evaluate the effect of posterior vitreomacular adhesion (VMA),
      documented by optical coherence tomography (OCT), on the outcome of anti-vascular
      endothelial growth factor (VEGF) treatment for exudative age-related macular
      degeneration (AMD). DESIGN: Retrospective comparative series. PARTICIPANTS: A
      total of 148 patients (148 eyes) who were newly diagnosed with exudative AMD and
      were treated by anti-VEGF in 1 eye from 2005 to 2008 with a minimum of 12 months
      follow-up. METHODS: We retrospectively reviewed OCT and medical records of 148
      patients with exudative AMD and categorized them according to the presence of
      posterior VMA into 2 subgroups: VMA (+) group (38 eyes) and VMA (-) group (110
      eyes). Best-corrected visual acuity (BCVA) and central retinal thickness (CRT)
      after anti-VEGF treatment were compared between the 2 groups at baseline; at 1,
      3, 6, and 12 months; and at the last visit (mean = 21 months). MAIN OUTCOME
      MEASURES: Mean changes in BCVA, which was converted to logarithm of the minimum
      angle of resolution (logMAR) values and CRT after anti-VEGF treatment. RESULTS:
      Mean BCVA significantly decreased over time in the VMA (+) group compared with
      the VMA (-) group (P = 0.039). At the last follow-up, mean BCVA had deteriorated
      from 0.87 logMAR (20/149 Snellen equivalent; baseline) to 0.98 logMAR (20/189
      Snellen equivalent) in the VMA (+) group, but improved from 0.82 logMAR (20/132
      Snellen equivalent, baseline) to 0.72 logMAR (20/104, Snellen equivalent) in the
      VMA (-) group (P = 0.028). In paired comparisons of BCVA between baseline and
      each follow-up visit, the VMA (-) group showed significant improvement of BCVA at
      every follow-up visit (P < 0.05); however, the VMA (+) group did not show
      significant visual improvement at any follow-up visit despite anti-VEGF treatment
      (P > 0.05). Comparison of mean CRT between baseline and each follow-up visit
      showed a statistically significant decrease at every follow-up in both groups (P
      < 0.05). CONCLUSIONS: Posterior VMA was associated with an inferior visual
      outcome after intravitreal anti-VEGF treatment for exudative AMD. Our results
      suggest that chronic tractional forces may antagonize the effect of anti-VEGF
      treatment, resulting in poor response to anti-VEGF treatment with patients with
      VMA.

PMID- 20678806
TI  - A cross-sectional study of the current treatment patterns in noninfectious
      uveitis among specialists in the United States.
AB  - PURPOSE: Corticosteroids (CS) are the only approved drug class for treatment of
      noninfectious uveitis by the U.S. Food and Drug Administration. Serious side
      effects are associated with chronic use of systemic CS; established guidelines
      recommend the use of steroid-sparing agents if control of uveitis cannot be
      achieved with <= 10 mg/day of prednisone (or equivalent) within 3 months. This
      study evaluated the treatment patterns among physicians who routinely manage
      patients with noninfectious uveitis to determine how treatment guidelines are
      followed. DESIGN: Cross-sectional, multicenter study conducted across the United
      States. PARTICIPANTS: Sixty ophthalmologists and 3 rheumatologists were recruited
      using payer reimbursement International Classification of Diseases, Ninth
      Revision codes. METHODS: Patient data were reported using a study-specific
      questionnaire. Physicians were also asked if they were aware of or used
      recommended treatment guidelines. MAIN OUTCOME MEASURES: Uveitis treatment
      patterns were compared with guidelines. RESULTS: Physicians managed a mean of
      5555 patients; patients with uveitis who required systemic CS treatment comprised
      approximately 5% of each physician's practice. A total of 580 patients with
      noninfectious uveitis were randomly selected for analyses. Anterior uveitis
      requiring systemic therapy was diagnosed in 168 patients (29%), intermediate
      uveitis was diagnosed in 140 patients (24%), posterior uveitis was diagnosed in
      150 patients (26%), and panuveitis was diagnosed in 122 patients (21%); 199
      patients (34%) had active disease. The mean time interval from the diagnosis of
      uveitis to the time of survey was 3.1 to 4.5 years. A systemic disorder was
      associated with uveitis in 16% to 54% of patients; 57% to 100% of patients
      received systemic immunosuppressive therapy. In all, 360 of 580 patients (62%)
      received systemic CS, with a mean initial daily dose of 44 mg, tapered to 34 mg
      prednisone (or equivalent) as maintenance dose. Among physicians surveyed, 75%
      did not use or were not aware of treatment guidelines for uveitis. CONCLUSIONS:
      The study reveals that the majority of physicians surveyed are not familiar with
      or do not adhere to currently recommended guidelines for management of uveitis.
      High CS doses are used to maintain control of disease, and there is a low level
      of awareness of recommended guidelines to treat noninfectious uveitis. The
      finding underscores the need to place further emphasis on educating the medical
      community and reinforcing treatment guidelines to improve the care of patients
      with uveitis.

PMID- 20678807
TI  - CdTe quantum dots (QDs) improve the affinities of baicalein and genistein for
      human serum albumin in vitro.
AB  - Baicalein and genistein were studied for the affinities for human serum albumin
      (HSA) in the presence and absence of three CdTe quantum dots (QDs) with different
      sizes. Three typical CdTe QDs with maximum emissions of 535 nm (green-emitting, G
      QDs), 598 nm (yellow-emitting, Y-QDs), and 654 nm (red-emitting, R-QDs) were
      tested. The fluorescence intensities of HSA decreased remarkably with increasing
      concentration of QDs. Baicalein resulted in an obvious blue-shift of the
      lambda(em) of HSA from 340 to 334 nm. However, the extents of blue-shifts induced
      by baicalein and genistein in the presence of QDs were much bigger than that in
      the absence of QDs. The quenching process of baicalein for HSA was easily
      affected by the QDs size than that of genistein. QDs increased the quenching
      constant from 136.97% to 162.24% for baicalein. However, QDs only increased the
      quenching constants from 20.56% to 32.23% for genistein. G-QDs, Y-QDs, and R-QDs
      increased the affinities of baicalein for HSA about 3.02%, 6.38% and 9.40%. G
      QDs, Y-QDs, and R-QDs increased the affinities of genistein for HSA about 2.56%,
      13.46% and 19.44%. The binding affinities of baicalein and genistein for HSA
      increased with increasing QDs size.

PMID- 20678808
TI  - The role of emotion regulation in auditory hallucinations.
AB  - Emotion regulation involves the use of strategies to influence the experience and
      expression of emotions. Anxiety and depression are strongly associated with the
      positive symptoms of schizophrenia, such as auditory hallucinations (AHs).
      Individuals usually try to down-regulate (decrease) such emotions, consequently
      abnormal or maladaptive use of one or more of these down-regulatory processes
      (e.g. increased use of expressive suppression or maladaptive attentional
      deployment, i.e. rumination/worry) may play an important role in AHs (e.g.
      increasing AH severity and distress). This study examined the self-reported use
      of a range of emotion regulation strategies in individuals with schizophrenia and
      current AHs (SZ AH; N=34) and healthy controls (N=34). Two separable dimensions
      of hallucinatory experiences (severity and distress) were assessed together with
      measures of anxiety, depression and happiness. Within the SZ AH group, greater
      use of expressive suppression was associated with an increase in severity of AHs
      and greater disruption in daily life. In addition, rumination was significantly
      positively correlated with the distress (but not with the severity) associated
      with AHs. Within the control group, expressive suppression, rumination and worry
      were associated with more anxiety/depression and less happiness, as predicted.
      The implications of different emotion regulation strategies for the treatment of
      individuals with schizophrenia and AHs are discussed.

PMID- 20678809
TI  - Expression of biologically active recombinant ferret (Mustela putorius furo)
      interleukin-8 from Escherichia coli.
AB  - The authors expressed recombinant ferret interleukin-8 protein (rfrIL-8) in
      Escherichia coli as a glutathione-S-transferase fusion protein. Western blot
      analyses revealed that anti-ovine IL-8 antibody reacted with rfrIL-8 at 10 kDa.
      To confirm that the rfrIL-8 was biologically active, the authors examined
      chemotaxis and respiratory burst activity of ferret polymorphonuclear blood cells
      (PMNs) exposed to rfrIL-8. The rfrIL-8 strongly induced chemotactic and
      respiratory burst activities in a statistically significant manner as compared
      with a negative control. Thus, the authors were able to successfully express
      biologically active rfrIL-8.

PMID- 20678810
TI  - Two HLA class I genes independently associated with multiple sclerosis.
AB  - OBJECTIVE: The risk of multiple sclerosis (MS) is influenced by HLA-DRB1, while
      protective effects have been proposed for HLA-A*02 and HLA-C*05. Our aim was to
      further understand the role of HLA class I in MS through a comprehensive
      investigation. METHODS: 1529 MS patients and 1814 controls from Sweden and Norway
      were genotyped for HLA-DRB1, HLA-A, and HLA-C. Simultaneous analysis of all
      alleles while adjusting for confounding was achieved using logistic regression.
      RESULTS: We observed independent effects of all three genes. We confirm the HLA
      A*02 (OR=0.73, p=9.2 x 10(-4)) association and report a novel effect of HLA-C*08
      (OR=1.85, p=0.0093). CONCLUSIONS: The HLA class I region contains two factors
      modulating MS risk, characterized by independent associations with HLA-A and HLA
      C.

PMID- 20678812
TI  - Effects of manganese and hypoxia on coelomocyte renewal in the echinoderm,
      Asterias rubens (L.).
AB  - Manganese (Mn) is a naturally abundant metal and particularly so in soft-bottom
      oceanic sediments where it generally occurs bound in a four-valent colloidal
      state as MnO2. When hypoxic conditions occur in bottom waters, the metal reduces
      to the bioavailable ion Mn2+ and can reach concentrations known to have
      immunotoxic effects in the crustacean Nephrops norvegicus, reducing numbers of
      circulating haemocytes as a consequence. However, we have previously shown that
      Mn seems to have a contrasting effect on the echinoderm Asterias rubens in which
      it triggers the proliferation of haematopoietic cells and increases coelomocyte
      numbers. Since elevated Mn levels mostly co-occur with hypoxia in nature, here we
      investigated whether hypoxia has a negative effect on haematopoiesis.
      Proliferation and differentiation of coelomocytes and cells in the coelomic
      epithelium of A. rubens were compared after 3 days of exposure to realistic
      levels of Mn, hypoxia or a combination of these two parameters. We can confirm
      that Mn elevated numbers of coelomocytes and increased proliferation of
      epithelial cells, but hypoxia did not affect these levels. However, hypoxia did
      affect differentiation of these cells as judged by investigating the expression
      of a Runt domain transcription factor, which was also cloned and sequenced.
      Through comparative quantification using a real time PCR technique, we found that
      exposure to hypoxia had a clearly stimulating effect on mRNA expression of Runt
      gene in both coelomocytes and epithelial cells. These results indicate that
      during hypoxic conditions the composition of coelomocyte sub-populations changed.

PMID- 20678811
TI  - Chronic exposure to the chemokine CCL3 enhances neuronal network activity in rat
      hippocampal cultures.
AB  - We examined the effect of chronic CCL3 treatment on the properties of cultured
      rat hippocampal neurons to gain an understanding of the neuronal effects of CCL3
      during neuroinflammatory disorders. Western blot assays showed that chronic
      exposure to CCL3 altered the level of specific neuronal and glial proteins and
      that CCL3 had no effect on neuronal survival. CCL3 treatment also altered
      intracellular Ca(2+) dynamics and increased Ca(2+) levels in hippocampal neurons,
      measured by fura-2 imaging techniques. Additionally, chronic CCL3 increased NMDA
      evoked Ca(2+) signals in the hippocampal neurons and increased NMDA receptor
      levels. These CCL3-induced neuroadaptive changes could play an important role in
      the CNS dysfunction associated with CNS disorders with a neuroinflammatory
      component.

PMID- 20678813
TI  - Five-year survival of patients after out-of-hospital cardiac arrest depending on
      age.
AB  - Patient's age belongs to the independent prognostic factors of patients after out
      of-hospital cardiac arrest (OHCA). This study aimed to evaluate the influence of
      age on 5-year survival in professionally cardio-pulmonary resuscitated patients
      with "primary cardiac" etiology OHCA. In this analysis of prospective multi
      centric study, from April 1, 2002 until August 31, 2004, a total of 560 patients
      were included (aged 16-97 years) from the East Bohemian region, for whom a
      professional cardio-pulmonary resuscitation for OHCA was attempted. In the age
      subgroup <70 years there were 307 patients and in the age subgroup >= 70 years
      there were 253 patients. Of the subgroup <70 years, 29 patients (10%) survived to
      year 5 (58% from the 50 patients surviving to day 30), and in the subgroup >= 70
      years, we had 4 patients surviving to year 5 (2%) (29% from the 14 patients
      surviving to day 30), respectively (Fisher's exact test; comparison in the all
      resuscitated patients: p < 0.001, in the population surviving to day 30: p =
      0.071). In conclusion, there was a trend towards a worse outcome in 5-year
      survival following OHCA in the patients aged >= 70 years. Nevertheless, these
      data support that prognosis OHCA of elders is not associated with universal
      dismal outcome.

PMID- 20678814
TI  - Relationship between admission albumin levels and rehabilitation outcomes in
      older patients.
AB  - The relationship between serum albumin level and rehabilitation outcome in older
      patients has not been fully explored. This study investigated this association in
      older Chinese patients. We studied 1604 patients in two geriatric convalescence
      hospitals. Admission albumin levels (g/l) were measured and segregated into three
      groups: <30 g/l; 30 to <35 g/l; >=35 g/l. Absolute functional and motor gain were
      determined by Barthel index (BI) and elderly mobility scale (EMS) and expressed
      as BI efficacy and EMS efficacy. BI and EMS efficiency were deduced by the
      efficacy divided by the length of hospital stay (LOS). Satisfactory motor and
      functional outcomes were defined as discharge EMS>=15 and BI>=75. Significant
      improvement in EMS and BI scores across all 3 albumin groups on discharge was
      observed, with lower scores in low albumin groups. The EMS and BI efficacy were
      the same in 3 albumin groups. However, EMS and BI efficiency were higher in the
      high albumin groups. Admission albumin was not independent predictors for
      satisfactory motor and functional outcomes. For satisfactory motor outcome
      (EMS>=15), female gender (p=0.0004), age (p=0.0009) and urinary incontinence
      (p=0.0076) were negative predictors while living at home (p=0.0028), admission
      EMS (p<0.001) and BI score (p=0.0004) were positive predictors. For satisfactory
      functional outcome (BI>=75), age (p=0.015) and urinary incontinence (p<0.001)
      were negative predictors while female gender (p=0.0024), LOS (p=0.033), C-MMSE
      (p<0.001), admission EMS (p=0.003) and BI (p<0.001) were positive predictors.
      Admission albumin levels were related to functional and motor efficiency, but not
      with absolute functional and motor gain. Albumin was not an independent predictor
      for satisfactory motor and functional outcome.

PMID- 20678815
TI  - Quetiapine augmentation of antidepressant treatment in elderly patients suffering
      from depressive symptoms: a retrospective chart review.
AB  - Depression in elderly patients is often characterized by poor responses to
      standard antidepressants. Several reports have suggested that quetiapine also may
      have antidepressant properties. The present study aimed to evaluate the efficacy
      of quetiapine augmentation in depressed elderly patients previously unresponsive
      to a full course of treatment. Medical charts of elderly depressed inpatients
      treated at a tertiary care psychiatric center during a 3-year period were
      reviewed. Clinical and demographic data were extracted from computerized records
      and analyzed. The primary outcome measure was the change on the clinical global
      impressions scale for improvement (CGI-I). Twenty depressed elderly inpatients
      received quetiapine augmentation during the study period. Prior to augmentation
      all had been treated with antidepressants. Baseline mean severity of depression
      was 6.40; severity after augmentation was significantly reduced to 3.25; the
      change in CGI-I was 2.10 (p<0.03). Mean quetiapine dose was 70 mg; mean duration
      of augmentation was 3.9 weeks. Five patients complained of somnolence. One
      patient discontinued psycho-tropics and switched to electroconvulsive therapy
      (ECT) due to life-threatening suicidal tendencies. We tentatively conclude that
      quetiapine augmentation for elderly depressed patients unresponsive to standard
      antidepressant treatment may be a safe and efficacious option. Further
      prospective studies need be carried out to support our observation.

PMID- 20678816
TI  - Impairments in mobility and balance in relation to frailty.
AB  - We set out to describe the relationship between impaired balance, mobility and
      frailty, and relate these to risk of death. We examined a subsample of 1295
      community-dwelling non-demented adults from the second wave of the Canadian Study
      of Health and Aging (CSHA), a prospective population-based cohort study. Frailty
      index (FI) scores were constructed from a standardized comprehensive geriatric
      assessment (FI-CGA). History of mobility impairments and falls were assessed.
      Timed-up-and-go (TUG) and functional reach (FR) performance were measured. The
      CSHA clinical frailty scale (CFS) was judged by a physician. Adverse outcomes
      were determined at CSHA-3, conducted 5 years later. The FI-CGA varied in
      association with impaired mobility and balance. A history of mobility problems
      was demonstrable at FI-CGA scores >0.12. This level of frailty also represented
      the most marked deterioration in performance measures (TUG and FR). FI-CGA scores
      best predicted mortality (HR 1.04+/-0.02), proving to be a dominating factor in
      multivariate regression models that included mobility and balance markers. Only
      at the upper range of FI-CGA reported (>0.45) did all participants demonstrate
      mobility impairment. Impaired balance and mobility contribute to frailty, but
      neither is sufficient to define a participant as frail.

PMID- 20678817
TI  - The relationship between the body mass index (BMI) and foot posture in elderly
      people.
AB  - We wanted to evaluate the postural characteristics of the feet of older people
      and their relationship with the BMI. We evaluated 227 older women and 172 older
      men with respect to the BMI, the arch index (AI) and the foot posture index
      (FPI). The obese women presented mean values for the AI significantly greater
      than those of the normal and overweight women. The means for some of the criteria
      of the FPI were significantly higher in the obese men. There was a positive
      correlation between the BMI and the AI and some of the FPI criteria. The
      conclusion was that obese women presented flatter feet while obese men presented
      more pronated feet, indicating a relationship between high BMI values and
      postural characteristics of the feet of subjects studied.

PMID- 20678818
TI  - How to assess frailty and the need for care? Report from the Study of Health and
      Drugs in the Elderly (SHADES) in community dwellings in Sweden.
AB  - Knowledge about the need for care of elderly individuals in community dwellings
      and the factors affecting their needs and support is limited. The aim of this
      study was to characterize the frailty of a population of elderly individuals
      living in community dwellings in Sweden in relation to co-morbidity, use of
      drugs, and risk of severe conditions such as malnutrition, pressure ulcers, and
      falls. In 2008, 315 elderly individuals living in community dwellings were
      interviewed and examined as part of the SHADES-study. The elderly demonstrated co
      morbidity (a mean of three diseases) and polypharmacy (an average of seven
      drugs). More than half the sample was at risk for malnutrition, one third was at
      risk for developing pressure ulcers, and nearly all (93%) had an increased risk
      of falling and a great majority had cognitive problems. Age, pulse pressure, body
      mass index, and specific items from the modified Norton scale (MNS), the Downton
      fall risk index (DFRI), and the mini nutritional assessment (MNA-SF) were related
      to different outcomes, defining the need for care and frailty. Based on the
      results of this study, we suggest a single set of items useful for understanding
      the need for care and to improve individual based care in community dwellings.

PMID- 20678819
TI  - Reliability of 4-m and 6-m walking speed tests in elderly people with cognitive
      impairment.
AB  - The purpose of this study was to evaluate the interrater and test-retest
      reliability of 4-m and 6-m walking speed tests in elderly people with cognitive
      impairment. 50 subjects aged 65 and over with cognitive impairment were selected
      from an adult day-care centre and a nursing home. To examine interrater
      reliability, 21 people were evaluated independently by two researchers who
      administered the 4-m and 6-m walking tests in each evaluation. For test-retest
      reliability, two observers administered the tests to the same 29 subjects, with a
      time interval of one week. Intraclass correlation coefficients (ICCs) were
      calculated to examine interrater and test-retest reliability. The ICCs for
      interrater reliability reached values of 0.96 and 0.88 for the 4-m and 6-m
      walking tests, respectively. In the test-retest study, the time interval was
      7.4+/-1.17 days. The ICCs were 0.91 for the 4-m test and 0.86 for the 6-m test.
      The results support the use of walking tests in elderly people with cognitive
      impairment.

PMID- 20678820
TI  - Underestimation of duration of ventricular activation by 12-lead ECG compared
      with direct measurement of activation duration derived from implanted pacemaker
      leads.
AB  - AIM: To determine extent to which 12-lead ECG QRS duration (QRSd) reflects
      ventricular activation duration compared with time relations from unpaced
      ventricular myograms in cardiac resynchronisation therapy (CRT) patients.
      METHODS: Left (LV) and right ventricular (RV) myograms were recorded during
      spontaneous rhythm from in-situ pacemaker leads in 77 patients receiving CRT; 14
      'normal activation' (unpaced QRSd <12 ms), 10 'simple left bundle branch block'
      (LBBB, QRSd 120-149 ms), 40 'advanced LBBB' (QRS >= 150 ms) and 13 right bundle
      branch block. Delay in onset (Q-LV, Q-RV) and duration (dur-LV, dur-RV) of
      activation were measured. Interventricular delay (DeltaT: Q-LV minus Q-RV) and
      'LV-overrun' (time between end 12-lead QRS and Q-end LV myogram) were calculated.
      RESULTS: 'Normal activation': Neither Q-LV, Q-RV (38 +/- 6 ms, 39 +/- 11 ms), nor
      dur-LV, dur-RV (66 +/- 9 ms, 81 +/- 25 ms) differed. DeltaT (-1 +/- 11 ms) was
      not different from zero, nor was Q-end LV (104 +/- 10 ms) different from QRSd
      (p=0.09). 'Simple LBBB': Q-LV (102 +/- 28 ms) was longer than 'normal activation'
      (p<0.001), but Q-RV, dur-LV, and dur-RV were no different. DeltaT (54 +/- 23 ms)
      was increased (p<0.001) and Q-end LV (187 +/- 48 ms) was longer than QRSd
      (p=0.005). 'Advanced LBBB': Q-LV (115 +/- 52 ms) was longer than 'normal
      activation' (p<0.001) but Q-RV was no different, so DeltaT (72 +/- 47 ms) was
      increased (p<0.001 compared to normal, p=0.04 compared to simple LBBB). Dur-LV
      (102 +/- 27 ms) was also prolonged, so Q-end LV (218 +/- 48 ms) was longer than
      QRSd (p<0.001). Longer LV-overrun was associated with longer DeltaT (p<0.001).
      CONCLUSIONS: Prolonged LV myopotential duration, associated with interventricular
      delay, is electrically silent on 12-lead QRSd. Unpaced surface QRSd
      underestimates true duration of native LV activation in CRT patients.

PMID- 20678821
TI  - Enhancement of ultrasonic thrombus imaging using novel liposomal bubbles
      targeting activated platelet glycoprotein IIb/IIIa complex--in vitro and in vivo
      study.
AB  - BACKGROUND: We developed perfluorocarbon gas-containing bubble liposomes (BL)
      with Arg-Gly-Asp (RGD) sequence-containing peptides, which bind to activated
      platelet glycoprotein IIb/IIIa complexes. The aim of this study was to examine
      the enhancing effects in ultrasonic thrombus imaging using these targeted BL in
      vitro and in vivo. METHODS: Liposomes composed of phosphatidylcholine and
      cholesterol were manufactured, and RGD peptide was attached by a covalent
      coupling reaction. Sonication was used to conjugate liposomes and perfluorocarbon
      gas, which formed targeted BL. In vitro, targeted BL were mixed with whole blood,
      which was allowed to coagulate while being shaken and rotated. In vivo, we
      administered targeted BL to 10 rabbits with acute thrombotic occlusions in the
      ilio-femoral artery. Thrombi were imaged using a 7.5-9 MHz linear transducer and
      a conventional ultrasound machine, and by scanning electron microscopy.
      Ultrasound images were digitized, and mean pixel gray-scale level (black = 0,
      white = 255) was measured. RESULTS: In vitro, mean pixel gray-scale level of the
      thrombi in targeted BL group was significantly higher than in control and non
      targeted BL groups (93 +/- 26 vs. 58 +/- 16, 48 +/- 9, p = 0.002, n = 10).
      Scanning electron microscopy revealed large amounts of targeted BL attached to
      the thrombi. In vivo, mean pixel gray-scale level of the thrombi with targeted BL
      was significantly higher (33.2 +/- 6.4 vs. 24.8 +/- 8.5, p = 0.0051, n = 10) than
      that before targeted BL administration. CONCLUSIONS: Perfluorocarbon gas
      containing BL with RGD peptide represent a novel echo contrast agent, which can
      markedly enhance ultrasonic thrombus imaging in vitro and in vivo, and may be
      useful for noninvasively diagnosing acute thrombotic vessel occlusion.

PMID- 20678823
TI  - Estimating deoxynivalenol contents of wheat samples containing different levels
      of Fusarium-damaged kernels by diffuse reflectance spectrometry and partial least
      square regression.
AB  - Fusarium head blight is a fungal disease causing yield losses and mycotoxin
      contamination in wheat and other cereals. Wheat kernels (cultivar Ritmo) were
      sampled in 2001, 2002, 2003, and 2006 and Fusarium-damaged kernels were separated
      from sound grain based on visual assessment. Subsequently, grain lots containing
      0, 20, 40, 60, 80, and 100% of damaged kernels were compiled. Each lot was split
      and the spectrometric reflectance (wavelengths 350-2500nm) was measured using
      subgroup one, while the concentration of the mycotoxin deoxynivalenol (DON) was
      determined by high-performance liquid chromatography in subgroup two. DON
      concentrations in batches classified as sound were not significantly different
      from 0. Estimating DON contents from the percentage of Fusarium-damaged kernels
      was impeded by vast variability, resulting in a coefficient of determination of
      0.49. Using spectrometric data subjected to partial least square regression
      allowed estimating DON contents with higher accuracy, in particular at elevated
      percentages of damaged kernels. The coefficient of determination was 0.84 for the
      relationship between DON contents estimated based on spectrometric data and the
      DON contents measured. The intercept of a regression line fitted through a plot
      of estimated versus measured DON contents was 0.89+/-3.61mg/kg. Since
      intercept+standard error was larger than the actual legal limit (1.25mg DON per
      kg dry grain in the European Union), the spectrometric procedure was still not
      precise enough to allow a reliable separation of grain samples with DON contents
      below 1.25mg/kg from samples with DON contents above the limit. However,
      spectrometric data also allowed estimating the DON content of the average damaged
      kernel within a given lot composed of sound and damaged kernels, which is
      probably the reason for the reduction of the fraction of unexplained variance by
      35% compared to the visual approach and illustrates that spectrometric approaches
      can make a contribution to reducing DON contents of wheat grain.

PMID- 20678822
TI  - Isolation and characterization of folate-producing bacteria from oat bran and rye
      flakes.
AB  - The aim of this research was to identify endogenous bacteria in commercial oat
      bran and rye flake products in order to study their folate production capability
      while maintaining the soluble dietary fibre components in physiologically active,
      unhydrolyzed form. Fourty-two bacteria were isolated from three different oat
      bran products and 26 bacteria from one rye flake consumer product. The bacteria
      were tentatively identified by sequence analysis of the 16S rRNA genes. The
      identification results revealed up to 18 distinct bacterial species belonging to
      13 genera in oat bran, and 11 species belonging to 10 genera in rye flakes. The
      most common bacterial genus in oat bran was Pantoea, followed by Acinetobacter,
      Bacillus, and Staphylococcus. Pantoea species dominated also in rye flakes. The
      extracellular enzymatic activities of the isolates were studied by substrate
      hydrolysis plate assays. Nearly 80% of the isolates hydrolyzed
      carboxymethylcellulose, whereas starch-degrading activities were surprisingly
      rare (10%). Beta-glucan was hydrolyzed by 19% of the isolates. Protease, lipase
      or xylanase activity was expressed by 24%, 29%, and 16%, respectively, of the
      isolates. Representatives of the genera Bacillus, Curtobacterium, Pedobacter, and
      Sanguibacter showed the highest diversity of enzymatic activities, whereas
      members of Janthinobacterium and Staphylococcus possessed no hydrolytic
      activities for the substrates studied. Production capability for total folates
      was analyzed from aerobic cell cultures at the stationary growth phase. The
      amount of folates was determined separately for the cell mass and the supernatant
      by microbiological assay. For comparison, folate production was also examined in
      a number of common lactic acid bacteria. The best producers in oat bran belonged
      to the genera Bacillus, Janthinobacterium, Pantoea, and Pseudomonas, and those in
      rye flakes to Chryseobacterium, Erwinia, Plantibacter, and Pseudomonas.
      Supernatant folate contents were high for Bacillus, Erwinia, Janthinobacterium,
      Pseudomonas, and Sanguibacter. Compared to the endogenous bacteria, lactic acid
      bacteria were poor folate producers. The results of this work provide the first
      insight into the potential role of endogenous microflora in modulating the
      nutrient levels of oat and rye based cereal products, and pave way to future
      innovations of nutritionally improved cereal foods.

PMID- 20678824
TI  - Application of an active alginate coating to control the growth of Listeria
      monocytogenes on poached and deli turkey products.
AB  - The relatively high prevalence of Listeria monocytogenes in ready-to-eat (RTE)
      turkey products is of great concern. The overall objective of this study was to
      develop antimicrobial edible coating formulations to effectively control the
      growth of this pathogen. The antimicrobials studied were nisin (500IU/g),
      Novagard CB 1 (0.25%), Guardian NR100 (500ppm), sodium lactate (SL, 2.4%), sodium
      diacetate (SD, 0.25%), and potassium sorbate (PS, 0.3%). These were incorporated
      alone or in binary combinations into five edible coatings: alginate, kappa
      carrageenan, pectin, xanthan gum, and starch. The coatings were applied onto the
      surface of home-style poached and processed deli turkey discs inoculated with
      ~3log CFU/g of L. monocytogenes. The turkey samples were then stored at 22
      degrees C for 7days. For poached and processed deli turkey, the coatings were
      found to be equally effective, with pectin being slightly less effective than the
      others. The most effective poached turkey treatments seemed to be SL (2.4%)/SD
      (0.25%) and Nisin (500IU/g)/SL (2.4%), which yielded final populations of 3.0 and
      4.9log CFU/g respectively compared to the control which was 7.9log CFU/g. For
      processed deli turkey, the most effective antimicrobial treatments seemed to be
      Nisin (500IU/g)/SD (0.25%) and Nisin (500IU/g)/SL (2.4%) with final populations
      of 1.5 and 1.7log CFU/g respectively compared to the control which was 6.5log
      CFU/g. In the second phase of the study, home-style poached and store-purchased
      roasted (deli) turkey inoculated with the pathogen at a level of ~3log CFU/g were
      coated with alginate incorporating selected antimicrobial combinations and stored
      for 8weeks at 4 degrees C. Alginate coatings supplemented with SL (2.4%)/PS
      (0.3%) delayed the growth of L. monocytogenes with final counts reaching 4.3log
      CFU/g (home-style poached turkey) and 6.5log CFU/g (roasted deli turkey)
      respectively while the counts in their untreated counterparts were significantly
      higher (P<0.05) reaching 9.9 and 7.9log CFU/g, respectively. This study therefore
      demonstrates the effectiveness of using alginate-based antimicrobial coatings to
      enhance the microbiological safety and quality of RTE poultry products during
      chilled storage.

PMID- 20678825
TI  - Examining effectiveness of medical interpreters in emergency departments for
      Spanish-speaking patients with limited English proficiency: results of a
      randomized controlled trial.
AB  - STUDY OBJECTIVES: This study examines whether availability of in-person
      professional interpreter services during emergency department (ED) visits affects
      satisfaction of limited English proficient patients and their health providers,
      using a randomized controlled trial. METHODS: We randomized time blocks during
      which in-person professional interpreters were available to Spanish-speaking
      patients in the EDs of 2 central New Jersey hospitals. We assessed the
      intervention's effects on patient and provider satisfaction through a multilevel
      regression model that accounted for the nesting of patients within time blocks
      and controlled for the patient's age and sex, hospital, and when the visit
      occurred (weekday or weekend). RESULTS: During the 7-month intake period, 242
      patients were enrolled during 101 treatment time blocks and 205 patients were
      enrolled during 100 control time blocks. Regression-adjusted results indicate
      that 96% of treatment group patients were "very satisfied" (on a 5-point Likert
      scale) with their ability to communicate during the visit compared with 24% of
      control group patients (odds ratio=72; 95% confidence interval 31 to 167). (Among
      control group members who were not very satisfied, responses ranged from "very
      dissatisfied" to "somewhat satisfied.") Similarly, physicians, triage nurses, and
      discharge nurses were more likely to be very satisfied with communication during
      treatment time blocks than during control time blocks. We did not assess acuity
      of illness or global measures of satisfaction. CONCLUSION: Use of in-person,
      professionally trained medical interpreters significantly increases Spanish
      speaking limited English proficient patients' and their health providers'
      satisfaction with communication during ED visits.

PMID- 20678826
TI  - [Pulmonary arterial hypertension as symptom of a limited form of systemic
      sclerosis in a nonagenerian].

PMID- 20678827
TI  - [Knowledge of the menopause in women 30-60 years old in the Vigo (Spain) Health
      Area].

PMID- 20678828
TI  - [Community-acquired methicillin-resistant Staphylococcus aureus infections in
      children].
AB  - INTRODUCTION: Community-acquired methicillin-resistant Staphylococcus aureus (CA
      MRSA) infections were first reported in the 1990s. Young, healthy individuals are
      frequently affected. The incidence of CA-MRSA in Spain is increasing. METHODS:
      All children seen between August 2006 and January 2009 with CA-MRSA infections
      were included. The S. aureus isolates were studied by conventional techniques,
      their antibiotic susceptibility by agar disk diffusion, the presence of mecA gene
      was detected by multiplex polymerase chain reaction (PCR) and the gene encoding
      the Panton-Valentine leukocidin (PVL) by conventional PCR. CA-MRSA colonization
      was studied both in patients and their family members. RESULTS: CA-MRSA was
      isolated in 15 samples from 12 patients, aged between 6 days and 14 years. Half
      of them were not native. Eight patients required hospital admission. The most
      common clinical presentation was skin and soft tissue infection (92%). Secondary
      CA-MRSA bacteraemia was present in two patients. All strains were PVL producers
      and two were resistant to macrolides associated to methicillin resistance and one
      of them was also resistant to lincosamides. An intra-familial transmission was
      identified. The clinical outcome was favourable in all patients. CONCLUSION: CA
      MRSA infections are emerging in Spain. Empirical treatment of skin and soft
      tissue infections should not be changed, since their incidence is still low. The
      drainage of CA-MRSA suppurative infections plays an important role in their
      treatment. Clindamycin or trimethoprim-sulfamethoxazole should be used for mild
      or moderate skin and soft tissue infections. Controlling the spread of these
      strains presents a challenge in the community today.

PMID- 20678829
TI  - Nursing students' perceived knowledge and attitude towards genetics.
AB  - The purpose of this study was to assess the knowledge base of nursing students
      regarding the topic of genetics and how this may change as a student progresses
      through the nursing program. A 70 item multiple-choice and dichotomous survey was
      given to freshman, sophomore, junior, and senior nursing students at a university
      school of nursing in the eastern part of the United States. Two hundred and
      seventy five pre-licensure nursing students, 255 females and 18 males, comprised
      the sample. A one-way analysis of variance (ANOVA) was performed and the results
      concluded that there was a significant difference among the freshmen, sophomores,
      juniors, and seniors in regards to having at least a 'minimal' knowledge or
      better of medical genetic terminology and conditions. Seniors reported a higher
      number of terms which they had at least a 'minimal' knowledge level or better
      than freshmen or sophomores. Also the juniors reported a higher number of terms
      which they had at least a 'minimal' knowledge level or better than sophomores.

PMID- 20678830
TI  - Management of oral carcinoma: benefits of early precancerous intervention.
AB  - Management of oral precancerous lesions remains polarised between interventional
      surgery and conservative treatment. We have previously shown the efficacy of
      carbon dioxide laser excision for both diagnosis and treatment of oral
      precancerous lesions. The aim of this study was to review the clinicopathological
      details of a group of patients in whom pre-existing but occult invasive carcinoma
      was diagnosed histopathologically in specimens excised by laser. We
      retrospectively reviewed 169 patients who attended the Maxillofacial Dysplasia
      Clinic at Newcastle General Hospital with single, new oral premalignant lesions
      over a 5-year period (2004-2008). They were all treated by laser excision of
      lesions that were confirmed to be dysplastic from examination of preoperative
      incisional biopsy specimens. There was a significant correlation between the
      results of diagnostic incisional, and laser excision, biopsy specimens (p <
      0.01), but 15 patients had signs of occult invasive carcinoma in the excision
      specimens (9%). In all cases the carcinomas were completely excised by the laser.
      Carbon dioxide laser excision is not only an effective treatment of precancerous
      lesions, but also facilitates early diagnosis and management of oral carcinoma at
      a stage when it is otherwise clinically undetectable.

PMID- 20678831
TI  - Making bone II: maxillary sinus augmentation with mononuclear cells--case report
      with a new clinical method.
AB  - We report a simplified method of using bone marrow aspirate concentrate (BMACTM)
      to regenerate hard tissue. The results suggest that BMACTM combined with a
      suitable biomaterial can form sufficient bone within 3 months for further
      implants to be inserted, and at the same time minimise morbidity at the donor
      site.

PMID- 20678833
TI  - Ubiquity of bisphenol A in the atmosphere.
AB  - Bisphenol A (BPA) is a suspected endocrine disruptor in the environment. However,
      little is known about its distribution and transport in the atmosphere. Here, the
      concentrations of BPA in the atmospheric aerosols from urban, rural, marine, and
      the polar regions were measured using solvent extraction/derivatization and gas
      chromatography/mass spectrometry technique. The concentrations of BPA (1-17,400
      pg m(-3)) ranged over 4 orders of magnitude in the world with a declining trend
      from the continent (except for the Antarctica) to remote sites. A positive
      correlation was found between BPA and 1,3,5-triphenylbenzene, a tracer for
      plastic burning, in urban regions, indicating that the open burning of plastics
      in domestic waste should be a significant emission source of atmospheric BPA. Our
      results suggest that the ubiquity of BPA in the atmosphere may raise a
      requirement for the evaluation of health effects of BPA in order to control its
      emission sources, for example, from plastic burning.

PMID- 20678832
TI  - Retrospective study on the cutaneous head and neck melanoma in Dorset (UK).
AB  - Trends in the incidence and the sites of primary malignant melanoma on the skin
      of head and neck in Dorset as well as the outcome of treated cases were
      overviewed for the first time. Increase in incidence rate of cutaneous head and
      neck melanoma from 1.3 per 100,000 in 2004 to 3.1 per 100,000 in 2007 was
      recorded. The most prevalent histogenetic type of cutaneous malignant melanoma on
      head and neck in our study was melanoma of superficial spreading type 35.1%
      (n=20) of all registered cases. Superficial spreading melanoma apart from being
      the most common type of malignant melanoma of the head and neck in Dorset also
      showed increase in the number of diagnosed cases of the reviewed years. It
      increased from 2 (22.2%) of all head and neck melanoma cases in 2004 to 7 (30.4%)
      in 2007. The average age at the time of diagnosis the cutaneous malignant
      melanoma of head and neck for both men and women was 73.5 years. Breslow
      thickness, Clark's level of invasion, tumour ulceration and anatomical site
      remained the most important prognostic factors. Correlation between Breslow
      thickness and Clark's level of invasion found to be stronger in men.

PMID- 20678834
TI  - Psychotherapeutic interventions for depressed, low-income women: a review of the
      literature.
AB  - Low-income women have very high rates of depression and also face a number of
      unique barriers that can prevent them from seeking, accepting, engaging in, or
      benefiting from psychotherapy treatment. Untreated depression often leads to
      deleterious psychological consequences for these women and their children, and
      may also diminish a woman's ability to improve her economic circumstances. We
      reviewed the literature on psychotherapeutic interventions for depressed, low
      income women, identifying a number of practical, psychological, and cultural
      barriers that often prevent them from engaging in psychotherapy. Next, we
      assessed the degree to which established intervention programs help women
      overcome these barriers. The data suggest that it is quite difficult to engage
      depressed, low-income women in psychotherapy, but that a number of standard
      psychotherapy approaches do show promise. However, we found that many of the
      currently available interventions fail to fully address the barriers that prevent
      this population from engaging in treatment. Moreover, the impact these
      interventions have on engagement and attrition rates or clinical improvements is
      often inadequately reported. We provide preliminary recommendations for
      clinicians who work with low-income women as well as suggestions for bolstering
      the literature base.

PMID- 20678835
TI  - The medicalisation of 'tall' girls: A discourse analysis of medical literature on
      the use of synthetic oestrogen to reduce female height.
AB  - Endocrine research in the 1930s increased and extended the use of sex hormones as
      medical therapies in an unprecedented way, especially for female ailments. In the
      1950s the therapeutic use of sex hormones extended to the treatment of 'tall'
      girls. Ambiguity in the definition of the 'tall' girl, the arbitrary nature of
      the treatment decision, and diversity in the therapeutic regimes highlight the
      problematic nature of this medical practice. Using linguistic repertoires to
      study the political and ideological implications found in the patterned use of
      language, this paper reports on a discourse analysis of the medical literature on
      treatment of tall girls between the 1950s and 1990s, when this treatment was at
      its peak. Three linguistic repertoires emerged: the institutional authority of
      medicine to determine the 'abnormality' of tall stature in females; the clinical
      knowledge and experience in the diagnosis of medical risk associated with tall
      stature in women; and using hormones as cosmetic therapy to (re)produce
      femininity in tall girls. All three related to the maintenance of the cultural
      representations and social expectations of femininity. With no evidence of
      psychological harm associated with tall stature in women, and no long-term
      studies of either effectiveness or benefit, over five decades clinicians
      persuaded themselves and their patients that tall stature required therapeutic
      intervention. The treatment of tall girls with high dose oestrogen must be viewed
      as the medicalisation of a normal physical attribute adversely related to the
      social construction of gender.

PMID- 20678836
TI  - Evidence based public health: A review of the experience of the National
      Institute of Health and Clinical Excellence (NICE) of developing public health
      guidance in England.
AB  - This paper describes the application of the principles of evidence based medicine
      to public health. It recounts the experience of the National Institute for Health
      and Clinical Excellence in England (NICE) which acquired a remit to develop
      public health guidance in 2005. Some of the history of the origins of the
      evidence based approach is described in the writings of Cochrane and others, and
      the way that this came to be a critical part of the NICE approach to developing
      clinical cost effectiveness is outlined. The challenge of applying these methods
      to an evidence base which is social and psychological as well as biomedical is
      considered. Key problems are identified: the breadth of the evidence base,
      different analytic levels of explanation, and the length of the causal chain
      between interventions and outcomes in public health.

PMID- 20678837
TI  - Boundary-lubricating ability and lubricin in synovial fluid of patients with
      temporomandibular joint disorders.
AB  - PURPOSE: This study was conducted to measure the boundary-lubricating ability and
      lubricin concentration of synovial fluid (SF) from patients with different stages
      of temporomandibular joint disorders (TMDs) and establish relationships between
      them. PATIENTS AND METHODS: According to the imaging and clinical findings, TMD
      patients were divided into 3 subgroups: displaced disc with reduction, displaced
      disc without reduction, and osteoarthritis. The boundary-lubricating ability of
      SF was determined by the coefficient of friction (COF) of SF in vitro with a
      friction apparatus. The lubricin concentrations were quantified by enzyme-linked
      immunosorbent assays. RESULTS: The COF of SF in TMD patients was significantly
      higher than that of healthy control subjects, but no observed difference was
      found among patient subgroups. Furthermore, a significant decline in lubricin
      concentrations was found in the group with osteoarthritis, whereas there was no
      significant change in the other groups. However, a significant correlation was
      not found between the COF and the lubricin concentrations in our study.
      CONCLUSIONS: These findings showed that distinct changes in lubricin and boundary
      lubricating ability in the SF occurred with different stages of TMDs.

PMID- 20678838
TI  - Ameloblastic carcinoma of the maxilla: a report of 2 cases.

PMID- 20678839
TI  - Acinic cell carcinoma of minor salivary glands: a clinical and
      immunohistochemical study.
AB  - PURPOSE: Acinic cell carcinoma is a rare malignant tumor of salivary glands. The
      purpose of this study is to evaluate the clinical outcome of acinic cell
      carcinoma in a group of 11 patients, who were treated in our clinic, and to
      discuss the management as well as the immunohistochemical features and prognosis
      of this carcinoma. MATERIALS AND METHODS: The study included 11 patients with
      acinic cell carcinoma of the minor salivary glands who were treated in our
      clinic. The patients were 7 women and 4 men. The patients' age ranged from 46 to
      83 years. The distribution of the primary sites was buccal mucosa (4)
      maxilla/maxillary sinus, etc, (2), hard palate (1), junction of soft/hard palate
      (1), lower lip (1), labio marginal sulcus (1), and vestibular sulcus and mandible
      (1). All patients were treated with surgery. Adjuvant radiotherapy was used in 3
      patients. Immunohistochemical assay of expression of Ki-67, p53, EGFR, and c-erbB
      2/neu markers was performed on specimens of all tumors. RESULTS: The mean follow
      up range was 2 to 15 years. Of the 11 patients, 7 were alive (2, 3, 4, 5, and 15
      years after the initial therapy). Two patients died of another cause free of the
      disease 9 and 10 years after the initial treatment, and 2 patients died of the
      disease (local recurrence, distant metastases 2 and 3 years later).
      Overexpression of immunohistochemical markers was evident for tumors with
      widespread metastases. CONCLUSIONS: Acinic cell carcinoma is a rare malignant
      tumor of the salivary glands, characterized by an indolent clinical course with
      the potential for both local recurrence and distant metastases. The
      immunohistochemical analysis of proliferation markers provides additional
      prognostic information for this tumor.

PMID- 20678840
TI  - Pattern of lymphatic spread from carcinoma of the buccal mucosa and its
      implication for less than radical surgery.
AB  - PURPOSE: With emerging evidence, focus is shifting to conservative neck
      procedures aimed at achieving good shoulder function without compromising
      oncologic safety. PATIENTS AND METHODS: Retrospective analysis of 100 consecutive
      neck dissections for carcinoma of the buccal mucosa was carried out to evaluate
      the pattern of lymphatic spread. Pathologic results were correlated with
      clinical/radiologic findings. Survival was calculated with the Kaplan-Meier
      method and log-rank test. RESULTS: Only 36 patients were found to harbor
      metastasis in the lymph nodes on pathologic examination. Most of these were
      present in levels I and II only. Skip metastasis was not detected in any patient.
      None of the patients was found to have involvement of level V nodes, whereas 1
      patient had involvement of level IV. Thirty-four patients developed recurrences;
      3-year disease-free survival was 48%. CONCLUSIONS: Lymphatic spread from
      carcinoma of the buccal mucosa is low. Involvement of level IV is seen in only 1%
      of patients. A more conservative approach to the neck in patients with carcinoma
      of the buccal mucosa is recommended.

PMID- 20678841
TI  - A comparative study on the extractions of partially impacted mandibular third
      molars with or without a buccal flap: a prospective study.
AB  - PURPOSE: The present report describes a flapless extraction method for partially
      impacted mandibular third molars and compares the effects of flap and flapless
      extractions of the teeth in terms of postoperative pain, swelling, and pocket
      depth of the second molar. PATIENTS AND METHODS: A prospective study was
      performed of 27 patients who underwent bilateral extraction of partially impacted
      mandibular third molars. Two molars in the same patient were extracted on each
      side, either with or without a buccal flap. RESULTS: The postoperative pain,
      swelling, and pocket depth of the second molar were all significantly greater on
      the side that underwent flap extraction than on the side that underwent flapless
      extraction (P < .05). CONCLUSIONS: Our results support the clinical use of
      flapless extractions when the distal surface of the crown is completely anterior
      to the anterior border of the mandibular ramus and the occlusal surface of the
      impacted tooth is level or nearly level with the occlusal plane of the second
      molar.

PMID- 20678842
TI  - Predictors of risk tolerance among oral surgery patients.
AB  - PURPOSE: This study attempts to provide insight on how the treatment preference
      for a mandible fracture and treatment received and its consequences are related
      to the patient's risk tolerance, as measured by the Standard Gamble (SG).
      PATIENTS AND METHODS: Data from a prospective cohort study of 203 subjects
      receiving treatment at the former King/Drew Medical Center in Los Angeles, CA,
      for either a mandible fracture (n = 98) or third molar removal (n = 105) were
      examined. Subjects were interviewed at 4 time points: on admission to the medical
      center and at 3 monthly follow-up visits. Risk tolerance for hypothetical
      treatment scenarios is measured by use of the SG, a health-value utility measure
      assessing the tradeoff between good outcomes and serious complications associated
      with treatment. Separate regression analyses with subsets of predictors
      (sociodemographic, psychosocial health, and clinical characteristics) were
      conducted and then synthesized by use of the significant predictors in separate
      analyses. RESULTS: For fracture subjects, there was a noticeable rise in the SG
      reports from admission to the 1-month follow-up. Their greater risk tolerance was
      associated with being older, receiving surgery, having a lower post-traumatic
      stress disorder score, and having a swollen jaw or face. For third molar
      subjects, SG did not change substantively over the course of the study.
      Predictors of greater risk tolerance for third molar subjects included the jaw or
      face being swollen and having to use less pain medication. CONCLUSIONS: Findings
      from this study show a preference for less invasive treatment, with the majority
      of both groups preferring wiring, and support the theory that treatment choices
      differ between subjects with different health states. Factors associated with
      risk tolerance include the patient's age, treatment received, psychosocial health
      state, experience with previous treatment, and value for oral health quality of
      life.

PMID- 20678843
TI  - Use of amniotic membrane as dressing in cervical necrotizing fasciitis.

PMID- 20678844
TI  - Is the median palatine cyst a distinct entity?

PMID- 20678845
TI  - Hemangioma concurrent with arteriovenous malformation in oral and maxillofacial
      region: report of a case and review of the literature.

PMID- 20678846
TI  - Maxillofacial rehabilitation of a microstomic patient after resection of nose,
      lip, and maxilla.
AB  - Few published reports have addressed the issues related to upper lip
      reconstruction. The present clinical report describes the maxillofacial
      rehabilitation of an edentulous patient who had been diagnosed with squamous cell
      carcinoma of the nasal septum and contiguous structures. The patient underwent
      total rhinectomy, anterior maxillectomy, and maxillary lip resection. Her
      maxillary lip was reconstructed with a bilateral cheek advancement flap, which
      allowed primary closure of the lip and aided in maintaining function of the
      orbicularis oris muscle. Microstomia was anticipated and was a consequence of
      this procedure. During primary resection, and before chemoradiotherapy, dental
      implants were successfully placed in the maxilla. These implants helped to retain
      a maxillary obturator prosthesis, which, in turn, helped to retain a silicone
      nasal prosthesis that restored the nasal defect. An intranasal acrylic resin
      framework with magnets aided in connecting the extraoral prosthesis with the
      intraoral prosthesis. The surgical and prosthodontic advantages of a cheek
      advancement flap and the treatment challenges in a microstomic patient are
      discussed.

PMID- 20678847
TI  - Comparative study of the prognosis of an extracorporeal reduction and a closed
      treatment in mandibular condyle head and/or neck fractures.
AB  - PURPOSE: The objective of this study was a comparison of the prognosis between an
      extracorporeal reduction technique and closed treatment of a mandibular condyle
      fracture. The relationship between condylar resorption and several clinical
      variables was also studied. PATIENTS AND METHODS: Seventy-one patients who had a
      mandibular condyle fracture took part in this study. Thirty-five patients
      (female: 7, male: 28, age: 30.46 +/- 14.27 years) were treated by extracorporeal
      reduction, and 36 patients (male: 24, female: 12, age: 24.28 +/- 9.99 years) were
      treated using a closed treatment. The presence of complications such as condylar
      resorption, malocclusion, nerve disorder, and disc displacement was evaluated
      with panoramic radiographs and clinical examinations 12 months after treatment.
      The relationships between the complications and other clinical variables were
      evaluated statistically. RESULTS: The anatomic site and fracture type were
      closely related to condyle resorption in the bivariate analysis. Condylar head
      fractures showed significantly higher condyle resorption than condylar neck
      fractures (P = .023). A complex or compound fracture showed significantly higher
      condyle resorption compared with a simple fracture (P = .006). Patients who had a
      complex/compound fracture were 34.366 times more likely to have condyle
      resorption compared with those who had a simple fracture (P = .002). The
      patient's age and treatment method were also significant predictors for condyle
      resorption. CONCLUSION: Fracture type was the strongest predictor of condylar
      resorption. Because treatment method and patient age were also related to the
      prognosis, the optimal treatment for mandibular condylar head and/or neck
      fractures should be individualized according to the patient's condition.

PMID- 20678848
TI  - Motor planning between 4 and 7 years of age: changes linked to executive
      functions.
AB  - In the present study, we adopted the conceptual frameworks of Miyake et al.
      (2000) (organization of executive functions) and Sergeant (2000) (linking
      executive function to motor behaviour) to assess developmental changes in
      executive functions and motor behaviour, using a planning task with a sample of 4
      7-years old children. More precisely, the aim of the study was to characterize
      the development of motor response planning between the ages of 4 and 7 as a
      measure of the integration of multiple executive function processes, namely
      inhibition, shifting and working memory, and to gain insight into the concurrent
      developmental contributions of these processes. Participants were divided into
      two groups: group 1 was composed of 24 children aged 4-5 years and group 2 was
      composed of 20 children aged 6-7 years. Each participant took tests for shifting,
      inhibition, working memory and motor planning (the egg-planning task). Our
      results suggest that the egg-planning task requires the inhibition of a pre
      potent but inappropriate response, and to a lesser extent the manipulation of
      working memory strategies. These results are discussed in relation to the
      development of each executive function component.

PMID- 20678849
TI  - [Advance care planning with COPD patients].

PMID- 20678850
TI  - Activating and resistance mutations of the epidermal growth factor receptor
      (EGFR) gene and non-small cell lung cancer: a clinical reality.
AB  - In non-small cell lung cancer, the EGFR gene mutations identify a patient sub
      population with different clinical characteristics and treatment responses to
      those that do not have these mutations. There are mutations that derive in
      increased sensitive to EGFR targeted therapy, as well as mutations that result in
      resistance. The determination of EGFR mutations involves a change in the
      therapeutic approach to lung cancer patients in current clinical practice. In
      this article we present a case of a patient suffering from a metastatic lung
      adenocarcinoma with an activating mutation on diagnosis, initially responding to
      treatment with erlotinib, who subsequently developed a secondary resistance due
      to acquiring the T790M mutation in exon 20 of the EGFR gene.

PMID- 20678851
TI  - [Sleep apnoea in patients of elderly: care activity in Spain (2002-2008)].
AB  - INTRODUCTION AND OBJECTIVE: There is a significant lack of scientific evidence on
      the role of SAHS in the elderly despite the increasing ageing of the population.
      The objective of the present study is to analyse the current healthcare situation
      in Spain on the diagnosis and treatment of sleep apnea in the population >=65
      years and its progress over the last few years. MATERIAL AND METHOD: Cross
      sectional study. Healthcare information was collected on the diagnosis and
      treatment of patients of both sexes and >=65 years suspected with having SAHS and
      referred to sleep units (SU) between 2002 and 2008. RESULTS: There were 51,229
      sleep studies performed in 16 SU. Of these, 24.3% were performed on subjects >=
      65 years (64.9% males), of which 71.5% had an AHI (apnoea-hypopnoea index) >10
      (68.6% treated with CPAP). There were no differences over time as regards mean
      age, mean AHI or percentage of studies done. A significant decrease was observed
      in the number of CPAP prescribed to males >=65 years from 2002 to 2005 (p=0.01)
      which subsequently increased up to 2008 (p=0.01). This phenomenon was not
      observed in women >=65 years. CONCLUSION: Despite the lack of evidence on the
      subject, healthcare activity due to suspected SAHS in the elderly population is
      intense, therefore it should be a priority to start clinical studies that may be
      able to answer key questions on the diagnosis and treatment of SAHS in this age
      group.

PMID- 20678852
TI  - Anaphylaxis to omeprazole. Cross-reactivity with the other proton pump
      inhibitors.

PMID- 20678853
TI  - Human seminal plasma hypersensitivity: an unusual indication for in vitro
      fertilization.

PMID- 20678854
TI  - Female sexual dysfunction.
AB  - In recent years female sexual dysfunction (FSD) is increasingly being recognised.
      It has a detrimental effect on a woman's quality of life and includes a range of
      disorders, and therefore adequate screening and diagnosis of patients are
      necessary before appropriate treatment can be commenced. As the etiology of FSD
      is often multi-factorial, arising from a multitude of organic pathologies in
      addition to having an underlying psychological basis, the treatment is often
      multidisciplinary. An understanding of the etiopathogenesis is therefore
      imperative to management. In the past 20 years major changes have occurred in our
      understanding, conceptualization and treatment of sexual dysfunction. In this
      article we look at the prevalence, classification, etiology and management of
      FSD.

PMID- 20678855
TI  - Aneuploidies detection in miscarriages and fetal deaths using multiplex ligation
      dependent probe amplification: an alternative for speeding up results?
AB  - OBJECTIVE: The aim of this prospective study was to apply the MLPA technique to
      products of miscarriages and fetal deaths in order to detect the more frequent
      chromosome aneuploidies and compare the results to conventional karyotyping.
      STUDY DESIGN: Multiplex ligation-dependent probe amplification (MLPA) is a
      relatively new molecular technique for targeted detection of common chromosomal
      aneuploidies, namely trisomy 13, 18, 21 and sex chromosomal abnormalities. The
      reliability and high accuracy of this technique constitute an alternative for
      rapid results in large scale testing. In this study, a total of 489 DNA samples
      from fetal tissue were used for aneuploidy detection of chromosomes 13, 18, 21, X
      and Y using a commercial MLPA kit (SALSA P095) and were simultaneously subjected
      to conventional karyotyping. RESULTS: MLPA was the only result available in 33%
      of the cases. A cytogenetic result was obtained in only 328/489 samples. MLPA
      detected 7.8% of chromosome aneuploidies. Among the total samples karyotyped,
      MLPA failed to detect some aneuploidies and the false-negative rate was 0.82%. As
      expected, ploidy changes and reciprocal translocations were not detected by this
      technique, but MLPA gave a conclusive result even in cases of mosaicism.
      CONCLUSION: The present data confirm that MLPA is a rapid, simple and reliable
      method for detection of chromosome 13, 18, 21, X and Y abnormalities in fetal
      tissue.

PMID- 20678856
TI  - Towards the ecotourism: a decision support model for the assessment of
      sustainability of mountain huts in the Alps.
AB  - This paper studies mountain hut infrastructure in the Alps as an important
      element of ecotourism in the Alpine region. To improve the decision-making
      process regarding the implementation of future infrastructure and improvement of
      existing infrastructure in the vulnerable natural environment of mountain
      ecosystems, a new decision support model has been developed. The methodology is
      based on qualitative multi-attribute modelling supported by the DEXi software.
      The integrated rule-based model is hierarchical and consists of two submodels
      that cover the infrastructure of the mountain huts and that of the huts'
      surroundings. The final goal for the designed tool is to help minimize the
      ecological footprint of tourists in environmentally sensitive and undeveloped
      mountain areas and contribute to mountain ecotourism. The model has been tested
      in the case study of four mountain huts in Triglav National Park in Slovenia.
      Study findings provide a new empirical approach to evaluating existing mountain
      infrastructure and predicting improvements for the future. The assessment results
      are of particular interest for decision makers in protected areas, such as Alpine
      national parks managers and administrators. In a way, this model proposes an
      approach to the management assessment of mountain huts with the main aim of
      increasing the quality of life of mountain environment visitors as well as the
      satisfaction of tourists who may eventually become ecotourists.

PMID- 20678857
TI  - Application of sludge-based carbonaceous materials in a hybrid water treatment
      process based on adsorption and catalytic wet air oxidation.
AB  - This paper describes a preliminary evaluation of the performance of carbonaceous
      materials prepared from sewage sludges (SBCMs) in a hybrid water treatment
      process based on adsorption and catalytic wet air oxidation; phenol was used as
      the model pollutant. Three different sewage sludges were treated by either
      carbonisation or steam activation, and the physico-chemical properties of the
      resultant carbonaceous materials (e.g. hardness, BET surface area, ash and
      elemental content, surface chemistry) were evaluated and compared with a
      commercial reference activated carbon (PICA F22). The adsorption capacity for
      phenol of the SBCMs was greater than suggested by their BET surface area, but
      less than F22; a steam activated, dewatered raw sludge (SA_DRAW) had the greatest
      adsorption capacity of the SBCMs in the investigated range of concentrations
      (<0.05 mol L(-1)). In batch oxidation tests, the SBCMs demonstrated catalytic
      behaviour arising from their substrate adsorptivity and metal content. Recycling
      of SA_DRAW in successive oxidations led to significant structural attrition and a
      hardened SA_DRAW was evaluated, but found to be unsatisfactory during the
      oxidation step. In a combined adsorption-oxidation sequence, both the PICA carbon
      and a selected SBCM showed deterioration in phenol adsorption after oxidative
      regeneration, but a steady state performance was reached after 2 or 3 cycles.

PMID- 20678858
TI  - A basic neural traffic noise prediction model for Tehran's roads.
AB  - We present an artificial neural network model to predict hourly A-weighted
      equivalent sound pressure levels (L(Aeq,1h)) for roads in Tehran at distances
      less than 4 m from the nearside carriageway edge. Our model uses the UK
      Calculation of Road Traffic Noise (CORTN) approach. Data were obtained from 50
      sampling locations near five roads in Tehran at nearside carriageway edge
      distances of less than 4 m. The data were randomly assigned to training, testing,
      and holdout subsets. Model training was carried out using the training and
      testing subsets and comprised 60% and 20% of the data, respectively. Model
      validation was performed using the remaining 20% of data as a holdout subset. We
      examine the overall model efficiency using non-parametric tests, such as the
      Wilcoxon matched-pairs signed-rank test for the training step and the Kolmogorov
      Smirnov test for two independent samples for the validation step. Our results
      indicate that a neural network approach can be applied for traffic noise
      prediction in Tehran in a statistically sound manner. The Wilcoxon matched-pairs
      signed-ranks test detects no significant difference between the absolute testing
      set errors of the developed neural network and a calibrated version of the CORTN
      model.

PMID- 20678859
TI  - Feasibility of mercury removal from simulated flue gas by activated chars made
      from poultry manures.
AB  - Increased emphasis on reduction of mercury emissions from coal fired electric
      power plants has resulted in environmental regulations that may in the future
      require application of activated carbons as mercury sorbents for mercury removal.
      At the same time, the quantity of poultry manure generated each year is large and
      technologies that take advantage of the material should be explored. The purpose
      of the work was to obtain preliminary data to investigate if activated chars made
      from different poultry manures could adsorb mercury from simulated flue gas. In
      laboratory experiments, activated chars made from chicken cake and litter removed
      mercury from the gas as well as a commercial alternative. It was also found that
      acid-washing these chars after activation may improve pore structure but does not
      influence the mercury removal efficiency. Activated chars were also made from
      turkey cake and litter. These raw materials produced activated chars with similar
      pore structure as those made from chicken manure, but they did not adsorb mercury
      as well. Acid-washing the turkey manure-based chars improved their performance,
      but this step would add to the cost of production. Preliminary evaluations
      suggest that unwashed activated chars may cost as little as $0.95/kg to produce.

PMID- 20678860
TI  - Anti-tumor and radiosensitization activities of the iron chelator HDp44mT are
      mediated by effects on intracellular redox status.
AB  - A novel iron chelator, HDp44mT, has been reported to have potent anti
      proliferative effects on cancer cells; however, the underlying mechanism of
      action is not well understood. In this study, we characterized the cytotoxic
      effect of HDp44mT in a chemo- and radio-resistant cell line (PC-3) of prostatic
      cancer origin. The activity of HDp44mT at nM concentrations was dependent on the
      intracellular GSH and atmospheric O(2) concentration, rather than iron
      deprivation. HDp44mT also radiosensitized PC-3 cells in a GSH-dependent manner.
      Interestingly, this radiosensitizing effect was observed under aerobic and, to a
      larger extent, hypoxic conditions, suggesting its potential utility as a
      radiosensitizer for some radioresistant tumors.

PMID- 20678861
TI  - Small compound inhibitors of basal glucose transport inhibit cell proliferation
      and induce apoptosis in cancer cells via glucose-deprivation-like mechanisms.
AB  - Cancer cells depend heavily on glucose as both energy and biosynthesis sources
      and are found to upregulate glucose transport and switch their main energy supply
      pathway from oxidative phosphorylation to glycolysis. These molecular and
      metabolic changes also provide targets for cancer treatment. Here we report that
      novel small molecules inhibited basal glucose transport and cell proliferation,
      and induced apoptosis in lung and breast cancer cells without affecting much
      their normal cell counterparts. Cancer cells survived the compound treatment lost
      their capability to proliferate. Mechanistic study indicates that the cancer cell
      inhibition by the test compounds has a component of apoptosis and the induced
      apoptosis was p53-independent and caspase 3-dependent, similar to those resulted
      from glucose deprivation. Compound treatment also led to cell cycle arrest in
      G1/S phase. The inhibition of cancer cell growth was partially relieved when
      additional glucose was supplied to cells, suggesting that the inhibition was due
      to, at least in part, the inhibition of basal glucose transport. When used in
      combination, the test compounds demonstrated synergistic effects with anticancer
      drugs cisplatin or paclitaxel in inhibition of cancer cell growth. All these
      results suggest that these glucose transport inhibitors mimic glucose deprivation
      and work through inhibiting basal glucose transport. These inhibitors have the
      potential to complement and replace traditional glucose deprivation, which cannot
      be used in animals, as new tools to study the effects of glucose transport and
      metabolism on cancer and normal cells.

PMID- 20678862
TI  - Cd(II) adsorption on various adsorbents obtained from charred biomaterials.
AB  - Cadmium could cause severe toxicant impact to living beings and is especially
      mobile in the environment. Biomass is abundant and effective to adsorb heavy
      metals, but is easy to be decomposed biologically which affects the reliability
      of long-run application. Several biomasses were charred with and without
      additives at temperatures less than 200 degrees C in this study. The prepared
      adsorbents were further testified to remove Cd(II) from aqueous solution.
      Equilibrium and kinetic studies were performed in batch conditions. The effect of
      several experimental parameters on the cadmium adsorption kinetics namely:
      contact time, initial cadmium concentration, sorbent dose, initial pH of solution
      and ionic strength was evaluated. Kinetic study confirmed (1) the rapid
      adsorption of Cd(II) on GC within 10 min and (2) the following gradual
      intraparticle diffusion inwards the sorbent at neutral pH and outwards at strong
      acidic solution. The grass char (GC) was selected for further test according to
      its high adsorption capacity (115.8 mg g(-1)) and affinity (Langmuir type
      isotherm). The Cd(II) removal efficiency was increased with increasing solution
      pH while the highest achieved at sorbent dosage 10.0 g L(-1). The ionic strength
      affects the sorption of Cd(II) on GC to a limited extent whereas calcium resulted
      in larger competition to the sorption sites than potassium. Spectroscopic
      investigation revealed the adsorption mechanisms between Cd(II) and surface
      functional groups involving amine, carboxyl and iron oxide. The long-term
      stability of the pyrolyzed grass char and the potential application in
      engineering practices were discussed.

PMID- 20678863
TI  - Solid phase studies and geochemical modelling of low-cost permeable reactive
      barriers.
AB  - A continuous column experiment was carried out under dynamic flow conditions in
      order to study the efficiency of low-cost permeable reactive barriers (PRBs) to
      remove several inorganic contaminants from acidic solutions. A 50:50 w/w waste
      iron/sand mixture was used as candidate reactive media in order to activate
      precipitation and promote sorption and reduction-oxidation mechanisms. Solid
      phase studies of the exhausted reactive products after column shutdown, using
      scanning electron microscopy (SEM), Fourier transform infrared spectroscopy
      (FTIR) and X-ray diffraction (XRD), confirmed that the principal Fe corrosion
      products identified in the reactive zone are amorphous iron (hydr)oxides
      (maghemite/magnetite and goethite), intermediate products (sulfate green rust),
      and amorphous metal sulfides such as amFeS and/or mackinawite. Geochemical
      modelling of the metal removal processes, including interactions between reactive
      media, heavy metal ions and sulfates, and interpretation of the ionic profiles
      was also carried out by using the speciation/mass transfer computer code PHREEQC
      2 and the WATEQ4F database. Mineralogical characterization studies as well as
      geochemical modelling calculations also indicate that the effect of sulfate and
      silica sand on the efficiency of the reactive zone should be considered carefully
      during design and operation of low-cost field PRBs.

PMID- 20678864
TI  - A compact process for the treatment of olive mill wastewater by combining wet
      hydrogen peroxide catalytic oxidation and biological techniques.
AB  - A system based on combined actions of catalytic wet oxidation and microbial
      technologies for the treatment of highly polluted OMW containing polyphenols was
      studied. The wet hydrogen peroxide catalytic oxidation (WHPCO) process has been
      investigated in the semi-batch mode at atmospheric pressure, using aluminium-iron
      pillared inter layer clay ((Al-Fe)PILC), under two different catalytic processes:
      ((Al-Fe)PILC/H(2)O(2)/ultraviolet radiations) at 25 degrees C and ((Al
      Fe)PILC/H(2)O(2)) at 50 degrees C. The results show that raw OMW was resistant to
      the photocatalytic process. However ((Al-Fe)PILC/H(2)O(2)), system operating at
      50 degrees C reduced considerably the COD, colour and total phenolic contents,
      and thus decreased the inhibition of the marine photobacteria Vibrio fischeri
      luminescence by 70%. This study also examined the feasibility of coupling WHPCO
      and anaerobic digestion treatment. Biomethanisation experiments performed with
      raw OMW or pre-treated OMW proved that pre-treatments with ((Al-Fe)PILC/H(2)O(2))
      system, for more than 2 h, resulted in higher methane production. Both untreated
      OMW as well as 2-h pre-treated OMW revealed as toxic to anaerobic bacteria.

PMID- 20678865
TI  - Vertical weight-bearing MRI provides an innovative method for standardizing
      Spurling test.
AB  - Although Spurling test, a foraminal compression test, is commonly used in
      clinical practice in patients with a suspected cervical radiculopathy, its
      protocol is still obscure. In undergoing this test, patients extend, laterally
      flex and slightly rotate neck to the symptomatic side, and then a pressure is
      applied on the top of patient's head by examiner. The test is scored as positive
      if it causes pain or tingling that starts in the shoulder and radiates distally
      to the elbow. But the range of neck motion and level of load are not clearly
      defined. Magnetic resonance imaging (MRI) has proved to be an excellent method of
      assessing the situation of cervical intervertebral foramen. Unfortunately the
      conventional MRI system is not able to fully achieve this goal because it can
      only examine patient in supine position while Spurling test needs to be performed
      in a sitting position. Here we hypothesize that vertical weight-bearing MRI
      provides an innovative method for researching and standardizing the protocols of
      Spurling test. The result will provide better knowledge of the mechanism of
      Spurling test. Standardization of the test will improve its sensitivity and rate
      of reproducibility.

PMID- 20678866
TI  - Macrophage migration inhibitory factor plays a pivotal role in hepatocellular
      carcinoma and may be a noninvasive imaging target.
AB  - Macrophage migration inhibitory factor (MIF) has emerged to play a central role
      in the control of the host inflammatory and immune response. Several reports have
      documented that MIF can inactivate the tumor suppresser activity of p53;
      overexpression of MIF was significantly higher in both the sera and the local
      lesions from patients with HCC than from patients with normal controls. These
      findings indicate that MIF may contribute to multiple aspects of tumor
      progression and neoplasia, thus MIF may be an effective therapeutic target
      molecule. We speculate that MIF is important for the development and progression
      of hepatocellular carcinoma, and can be used as a marker for tumor detection.

PMID- 20678867
TI  - Can poor sleep affect skin integrity?
AB  - Modern society has reported a decline in sleep time in the recent decades. This
      reduction can increase the morbidity and mortality of several diseases and leads
      to an immunosuppressive state. The skin is the largest organ in the human body
      and collagen, its main component, has a key role in the structure and integrity
      of the organism. The entire sequence of events necessary during collagen
      formation can be affected by endogenous and exogenous factors. A variety of
      studies in the literature have shown that sleep plays a role in restoring immune
      system function and that changes in the immune response may affect collagen
      production. Several studies of prolonged sleep deprivation suggest a break in
      skin barrier function and mucous membranes. In fact, the reduction of sleep time
      affects the composition and integrity of various systems. Thus, we hypothesized
      that lack of sleep as well as other types of stress can impair skin integrity.

PMID- 20678868
TI  - Evolution of the volatile compounds of ripened sausages as a function of both
      storage time and composition of packaging atmosphere.
AB  - An experimental investigation was carried out to study the evolution of the
      volatile compounds of ripened sausages as a function of both storage time (time)
      and composition of packaging atmosphere (MAP). Ripened sausages, prepared at an
      industrial plant, were packed applying three different atmosphere compositions
      and were stored for three months. The obtained data evinced that the evolution of
      the volatile compounds was significantly related to the variable time more than
      to the variable MAP. The main volatile compounds were those derived from spices.
      Among them, Delta3-carene was the most abundant and a significant decrease was
      observed during storage (p<0.05). The volatile compounds derived from lipid
      autoxidation showed generally a significant increase during storage, suggesting
      the raise of lipid oxidation also at low oxygen concentration. Moreover, octanal
      and nonanal were significantly influenced by the atmosphere composition, with the
      highest values in samples packed at the lowest CO2 concentration.

PMID- 20678869
TI  - Four-dimensional measurement of the displacement of internal fiducial markers
      during 320-multislice computed tomography scanning of thoracic esophageal cancer.
AB  - PURPOSE: To investigate the three-dimensional movement of internal fiducial
      markers placed near esophageal cancers using 320-multislice CT. METHODS AND
      MATERIALS: This study examined 22 metal markers in the esophageal wall near the
      primary tumors of 12 patients treated with external-beam photon radiotherapy.
      Motion assessment was analyzed in 41 respiratory phases during 20 s of cine CT in
      the radiotherapy position. RESULTS: Motion in the cranial-caudal (CC) direction
      showed a strong correlation (R(2) > 0.4) with the respiratory curve in most
      markers (73%). The average absolute amplitude of the marker movement was 1.5 +/-
      1.6 mm, 1.6 +/- 1.7 mm, and 3.3 +/- 3.3 mm in the left-right (LR), anterior
      posterior (AP), and CC directions, respectively. The average marker displacements
      in the CC direction between peak exhalation and inhalation for the 22 clips were
      1.1 mm (maximum, 5.5 mm), 3.0 mm (14.5 mm), and 5.1 mm (16.3 mm) for the upper,
      middle, and lower thoracic esophagus, respectively. CONCLUSIONS: Motion in
      primary esophagus tumor was evaluated with 320-multislice CT. According to this
      study, 4.3 mm CC, 1.5 mm AP, and 2.0 mm LR in the upper, 7.4 mm CC, 3.0 mm AP,
      and 2.4 mm LR in the middle, and 13.8 mm CC, 6.6 mm AP, and 6.8 mm LR in the
      lower thoracic esophagus provided coverage of tumor motion in 95% of the cases in
      our study population.

PMID- 20678870
TI  - Motor-function and exercise capacity in children with major anatomical congenital
      anomalies: an evaluation at 5 years of age.
AB  - BACKGROUND: Children with major anatomical congenital anomalies (CA) often need
      prolonged hospitalization with surgical interventions in the neonatal period and
      thereafter. Better intensive care treatment has reduced mortality rates, but at
      the cost of more morbidity. AIM: To study motor-function and exercise capacity in
      five-year-old children born with CA, and to determine whether motor-function and
      exercise capacity differ according to primary diagnosis. STUDY DESIGN:
      Descriptive study. SUBJECTS: One-hundred-and-two children with the following CA:
      congenital diaphragmatic hernia (CDH) n=24, esophageal atresia (EA) n=29, small
      intestinal anomalies (SIA) n=25, and abdominal wall defects (AWD) n=24. OUTCOME
      MEASURES: Overall and subtest percentile scores of the Movement-Assessment
      Battery for Children (M-ABC) were used to measure motor skills. Endurance time on
      the Bruce treadmill test was used to determine maximal exercise capacity.
      RESULTS: Motor-function: Seventy-three children (71.6%) had an overall percentile
      score within the normal range, 18 (17.6%) were classified as borderline, and 11
      (10.8%) had a motor problem. This distribution was different from that in the
      reference population (Chi square: p=0.001). Most problems were encountered in
      children with CDH and EA (p=0.001 and 0.013, respectively). Ball skills and
      balance were most affected. Exercise capacity: Mean standard deviation score
      (SDS) endurance time=-0.5 (SD: 1.3); p=0.001; due to poor exercise performance in
      CDH and EA patients. CONCLUSIONS: Children with major anatomical CA and
      especially those with CDH and EA are at risk for delayed motor-function and
      disturbed exercise capacity.

PMID- 20678871
TI  - Effect of number of motile, frozen-thawed boar sperm and number of fixed-time
      inseminations on fertility in estrous-synchronized gilts.
AB  - There are advantages for use of frozen-thawed boar sperm (FTS) as a tool for
      preservation and transfer of valuable genetic material, despite its practical
      limitations. It was hypothesized that increasing the number of motile FTS and
      number of fixed-time artificial inseminations (AI) would improve pregnancy rate
      and litter size. Semen from six boars was frozen in 0.5mL straws at
      500x10(6)cells/mL. Gilts approximately 170 days of age, were induced into estrus
      with PG600 and synchronized using MATRIX (synthetic progestagen). Following last
      feeding of MATRIX (LFM), gilts were checked twice daily for estrus. At onset of
      estrus, gilts were randomly assigned in a 3x2 factorial treatment design to
      receive 1x10(9) motile FTS (n=19), 2x10(9) motile FTS (n=19), 4x10(9) motile FTS
      (n=19) in a single AI at 32h after onset of estrus, or 1x10(9) motile FTS (n=18),
      2x10(9) motile FTS (n=17), or 4x10(9) motile FTS (n=19) in each of the two AI at
      24 and 32h following onset of estrus. Ultrasonography was performed at 12h
      intervals after estrus to estimate time of ovulation. Reproductive tracts were
      collected 28-34 days following AI. Estrus occurred at 139+/-2h (mean+/-SE) after
      LFM and ovulation at 33+/-1h following onset of estrus. Dose and number of
      inseminations did not interact or individually influence pregnancy rate at
      slaughter (73+/-4.2%) or numbers of normal fetuses (10.8+/-0.5). However, number
      of fetuses tended (P=0.14) to increase with double AI but not with dose. Boar did
      not affect pregnancy rate but did affect number of normal fetuses and embryonic
      survival (P<0.01). Longer intervals from insemination to ovulation reduced
      pregnancy rate (P<0.05), number of normal fetuses (P<0.001), and embryonic
      survival (P<0.01). Ovarian abnormalities at slaughter were associated with
      reduced pregnancy rate (P<0.001). The results of this experiment indicate that a
      double insemination using 2x10(9) motile sperm would produce the greatest number
      of piglets with fewest numbers of frozen sperm used, while double AI with 1x10(9)
      motile sperm would be most practical for pig production with limited genetic
      resources. Fertility was also influenced by boar, interval from insemination to
      ovulation, and gilt ovarian abnormalities.

PMID- 20678872
TI  - Short-term grazing of lucerne and chicory increases ovulation rate in
      synchronised Merino ewes.
AB  - This study evaluated the ability of short-term grazing of live=green pasture to
      increase ovulation rate during late summer when annual pasture is generally dead
      and of low quality. Ovulation rates, measured by the number of corpora lutea,
      were compared between 4 nutritional treatments: senesced phalaris (Phalaris
      aquatica), phalaris plus 500g lupin grain per day, lucerne (Medicago sativa) or
      chicory (Chicorum intybus) pastures. The study used 100 Merino ewes per
      treatment, divided between 2 replicates. The experiment was repeated in 3 years;
      February 2006, and January 2007 and 2008. Oestrus was synchronised and the ewes
      grazed the pastures for 9 days prior to ovulation at times corresponding to days
      8-17 of the cycle in 2006, and days 6-14 in 2007 and 2008. The proportion of ewes
      producing multiple ovulations was higher (P<0.05) in the lucerne and chicory
      (0.36, 0.38) than the phalaris (0.27), and intermediate in the lupin (0.33)
      treatment. Regression analysis showed that the proportion of ewes with multiple
      ovulations increased with the quantity of live herbage (P<0.04). Responses were
      achieved even at low levels of live herbage with 90% of the maximum proportion of
      multiples occurring at 350kg DM/ha. It is concluded that providing short-term
      grazing of live chicory or lucerne to ewes can increase ovulation rates relative
      to ewes grazing senesced phalaris and to levels similar to those achieved by
      lupin grain supplementation.

PMID- 20678873
TI  - Characterization of reproductive disorders in ewes given an intrauterine dose of
      Toxoplasma gondii tachyzoites during the intrauterine insemination.
AB  - The aim of this study was to characterize the reproductive disorders in the acute
      and chronic phases in ewes experimentally infected with different doses of
      Toxoplasma gondii during artificial insemination occurred. Animals (n=41) were
      divided into three experimental groups: in the group 1 (G1, n=15), animals were
      inseminated using contaminated semen containing 6.5*104 tachyzoites; in the group
      2 (G2, n=15), animals were inseminated with contaminated semen containing 4*107
      tachyzoites and in the group 3 (G3, n=11), animals were inseminated using
      tachyzoite-free semen, serving as control group. Parasitemia and seroconversion
      were observed in 28 of 30 and 20 of 30, respectively, from the seventh day after
      infection. Embryonic reabsorption was observed in the acute phase in ewes from G1
      and G2. Persistent anestrus, hydrometra, mucometra and follicular cysts were
      observed in the second phase of the experiment in animals from G1 and G2.
      Histopathological lesions similar to those of toxoplasmosis were found in the
      placentas. In conclusion, artificial insemination using semen containing
      experimentally added tachyzoites can establish toxoplasmosis in ewes and cause
      reproductive pathologies during the acute and chronic phases of the disease.

PMID- 20678874
TI  - A narrative review on women and cardiac rehabilitation: program adherence and
      preferences for alternative models of care.
AB  - Despite the preponderance of evidence on the numerous benefits of CR, it remains
      largely under-utilized in women. The objective of this narrative review was to
      summarize and synthesize the literature on women and CR with regard to outcomes,
      adherence, and preferences for alternative models of CR. Studies of the
      effectiveness of CR have generally revealed no major differences between men and
      women. However, female-specific data are lacking on the effect of CR on mortality
      and morbidity. Research suggests that women and men may be equally likely to
      prefer home-based to hospital-based CR services. Women's preferences for and
      outcomes in, women-only CR are beginning to be uncovered. Discussing program
      model options with female cardiac patients and referring to preferred types may
      be the appropriate approach until further evidence is available.

PMID- 20678875
TI  - Tetramine poisoning: A case report and review of the literature.
AB  - BACKGROUND: Tetramethylene disulfotetramine (TETS), a banned neurotoxic
      rodenticide, has accounted for numerous intentional and unintentional poisonings
      in mainland China. Since the first known case of human illness caused by
      tetramine occurred in NewYork, in May 2002, TETS has caused more than 50 human
      poisonings in Western countries. AIM: To analyze pathological changes of TETS
      poisoning and to provide evidence for forensic identification. METHODS: We report
      the case of a 28-year-old female who suffered from tetramine poisoning and died
      of multi-organ failure. We also performed a retrospective study of 40 cases of
      poisoning, from pathological autopsy reports, by analyzing and summarizing the
      related the literature from 1996 to 2010. Based on pathologic autopsies and the
      literature, we summarize the pathological changes related to tetramine poisoning.
      RESULTS: Signs of asphyxia were obvious upon pathological examination. Edema and
      congestion of organs, particularly in the brain, were seen in all cases.
      Subarachnoid and cerebral hemorrhaging were also common signs of tetramine
      poisoning. CONCLUSION: In forensic practice, tetramine poisoning should be
      considered when the patient has signs of abnormal excitation of the central
      nervous system, convulsions, hyperspasmia, and cerebral hemorrhage.

PMID- 20678876
TI  - One-step preparation of amino-PEG modified poly(methyl methacrylate) microchips
      for electrophoretic separation of biomolecules.
AB  - A simple method for a chemical surface modification of poly(methyl methacrylate)
      (PMMA) microchips with amino-poly(ethyleneglycol) (PEG-NH(2)) by nucleophilic
      addition-elimination reaction was developed to improve the separation efficiency
      and analytical reproducibility in a microchip electrophoresis (MCE) analysis of
      biomolecules such as proteins and enantiomers. In our procedure, the PEG chains
      were robustly immobilized only by introducing an aqueous solution of PEG-NH(2)
      into the PMMA microchannel. The electroosmotic mobilities on the modified chips
      remained almost constant during 35 days with 37 runs without any recoating. The
      PEG-NH(2) modified chip provided a fast, reproducible, efficient MCE separation
      of proteins with a wide variety of isoelectric points within 15s. Furthermore,
      the application of the modified chip to affinity electrophoresis using bovine
      serum albumin gave a good chiral separation of amino acids.

PMID- 20678877
TI  - Therapeutic distant organ effects of regional hypothermia during mesenteric
      ischemia-reperfusion injury.
AB  - INTRODUCTION: Mesenteric ischemia-reperfusion injury (IRI) leads to systemic
      inflammation and multiple organ failure in clinical and laboratory settings. We
      investigated the lung structural, functional, and genomic response to mesenteric
      IRI with and without regional intraischemic hypothermia (RIH) in rodents and
      hypothesized that RIH would protect the lung and preferentially modulate the
      distant organ transcriptome under these conditions. METHODS: Sprague-Dawley rats
      underwent sham laparotomy or superior mesenteric artery occlusion (SMAO) for 60
      minutes with or without RIH. Gut temperature was maintained at 15 degrees -20
      degrees C during SMAO, and systemic normothermia (37 degrees C) was maintained
      throughout the study period. At 6 or 24 hours, lung tissue was collected for (1)
      histology, (2) myeloperoxidase activity, (3) bronchoalveolar lavage (BAL) fluid
      protein concentrations, (4) lung wet/dry ratios, and (5) total RNA isolation and
      hybridization to Illumina's Sentrix BeadChips (>22,000 probes) for gene
      expression profiling. Significantly affected genes (false discovery rate <5% and
      fold change >=1.5) were linked to gene ontology (GO) terms using MAPPFinder, and
      hypothermia-suppressed genes were further analyzed with Pubmatrix. RESULTS:
      Mesenteric IRI-induced lung injury, as evidenced by leukocyte trafficking,
      alveolar hemorrhage, and increased BAL protein and wet/dry ratios, and activated
      a proinflammatory lung transcriptome compared with sham. In contrast, rats
      treated with RIH exhibited lung histology, BAL protein, and wet/dry ratios
      similar to sham. At 6 hours, GO analysis identified 232 hypothermia-suppressed
      genes related to inflammation, innate immune response, and cell adhesion, and 33
      hypothermia-activated genes related to lipid and amine metabolism and defense
      response. Quantitative real-time polymerase chain reaction validated select array
      changes in top hypothermia-suppressed genes lipocalin-2 (lcn-2) and chemokine
      ligand 1 (CXCL-1), prominent genes associated with neutrophil activation and
      trafficking. CONCLUSIONS: Therapeutic hypothermia during SMAO provides distant
      organ protection and preferentially modulates the IRI-activated transcriptome in
      the rat lung. This study identifies potential novel diagnostic and therapeutic
      targets of mesenteric IRI and provides a platform for further mechanistic study
      of hypothermic protection at the cellular and subcellular level.

PMID- 20678878
TI  - Results of the randomized, placebo-controlled clopidogrel and acetylsalicylic
      acid in bypass surgery for peripheral arterial disease (CASPAR) trial.
AB  - OBJECTIVE: Dual antiplatelet therapy with clopidogrel plus acetylsalicylic acid
      (ASA) is superior to ASA alone in patients with acute coronary syndromes and in
      those undergoing percutaneous coronary intervention. We sought to determine
      whether clopidogrel plus ASA conferred benefit on limb outcomes over ASA alone in
      patients undergoing below-knee bypass grafting. METHODS: Patients undergoing
      unilateral, below-knee bypass graft for atherosclerotic peripheral arterial
      disease (PAD) were enrolled 2 to 4 days after surgery and were randomly assigned
      to clopidogrel 75 mg/day plus ASA 75 to 100 mg/day or placebo plus ASA 75 to 100
      mg/day for 6 to 24 months. The primary efficacy endpoint was a composite of index
      graft occlusion or revascularization, above-ankle amputation of the affected
      limb, or death. The primary safety endpoint was severe bleeding (Global
      Utilization of Streptokinase and Tissue plasminogen activator for Occluded
      coronary arteries [GUSTO] classification). RESULTS: In the overall population,
      the primary endpoint occurred in 149 of 425 patients in the clopidogrel group vs
      151 of 426 patients in the placebo (plus ASA) group (hazard ratio [HR], 0.98; 95%
      confidence interval [CI], 0.78-1.23). In a prespecified subgroup analysis, the
      primary endpoint was significantly reduced by clopidogrel in prosthetic graft
      patients (HR, 0.65; 95% CI, 0.45-0.95; P = .025) but not in venous graft patients
      (HR, 1.25; 95% CI, 0.94-1.67, not significant [NS]). A significant statistical
      interaction between treatment effect and graft type was observed (P(interaction)
      = .008). Although total bleeds were more frequent with clopidogrel, there was no
      significant difference between the rates of severe bleeding in the clopidogrel
      and placebo (plus ASA) groups (2.1% vs 1.2%). CONCLUSION: The combination of
      clopidogrel plus ASA did not improve limb or systemic outcomes in the overall
      population of PAD patients requiring below-knee bypass grafting. Subgroup
      analysis suggests that clopidogrel plus ASA confers benefit in patients receiving
      prosthetic grafts without significantly increasing major bleeding risk.

PMID- 20678879
TI  - Prevention and treatment of the postthrombotic syndrome.

PMID- 20678881
TI  - The Pacific Vascular Symposium 6: The Venous Ulcer Summit in perspective.

PMID- 20678880
TI  - Hyperglycemia limits experimental aortic aneurysm progression.
AB  - OBJECTIVE: Diabetes mellitus (DM) is associated with reduced progression of
      abdominal aortic aneurysm (AAA) disease. Mechanisms responsible for this negative
      association remain unknown. We created AAAs in hyperglycemic mice to examine the
      influence of serum glucose concentration on experimental aneurysm progression.
      METHODS: Aortic aneurysms were induced in hyperglycemic (DM) and normoglycemic
      models by using intra-aortic porcine pancreatic elastase (PPE) infusion in
      C57BL/6 mice or by systemic infusion of angiotensin II (ANG) in apolipoprotein E
      deficient (ApoE(-/-)) mice, respectively. In an additional DM cohort, insulin
      therapy was initiated after aneurysm induction. Aneurysmal aortic enlargement
      progression was monitored with serial transabdominal ultrasound measurements. At
      sacrifice, AAA cellularity and proteolytic activity were evaluated by
      immunohistochemistry and substrate zymography, respectively. Influences of serum
      glucose levels on macrophage migration were examined in separate models of
      thioglycollate-induced murine peritonitis. RESULTS: At 14 days after PPE
      infusion, AAA enlargement in hyperglycemic mice (serum glucose >= 300 mg/dL) was
      less than that in euglycemic mice (PPE-DM: 54% +/- 19% vs PPE: 84% +/- 24%, P <
      .0001). PPE-DM mice also demonstrated reduced aortic mural macrophage
      infiltration (145 +/- 87 vs 253 +/- 119 cells/cross-sectional area, P = .0325),
      elastolysis (% residual elastin: 20% +/- 7% vs 12% +/- 6%, P = .0209), and
      neovascularization (12 +/- 8 vs 20 +/- 6 vessels/high powered field, P = .0229)
      compared with PPE mice. Hyperglycemia limited AAA enlargement after ANG infusion
      in ApoE(-/-) mice (ANG-DM: 38% +/- 12% vs ANG: 61% +/- 37% at day 28). Peritoneal
      macrophage production was reduced in response to thioglycollate stimulation in
      hyperglycemic mice, with limited augmentation noted in response to vascular
      endothelial growth factor administration. Insulin therapy reduced serum glucose
      levels and was associated with AAA enlargement rates intermediate between
      euglycemic and hyperglycemic mice (PPE: 1.21 +/- 0.14 mm vs PPE-DM: 1.00 +/- 0.04
      mm vs PPE-DM + insulin: 1.14 +/- 0.05 mm). CONCLUSIONS: Hyperglycemia reduces
      progression of experimental AAA disease; lowering of serum glucose levels with
      insulin treatment diminishes this protective effect. Identifying mechanisms of
      hyperglycemic aneurysm inhibition may accelerate development of novel clinical
      therapies for AAA disease.

PMID- 20678882
TI  - A clinicopathologic study of immunoglobulin G4-related sclerosing disease of the
      thoracic aorta.
AB  - OBJECTIVE: Immunoglobulin G4-related sclerosing disease (IgG4-SD) has recently
      been reported to occur in the cardiovascular system and manifest as inflammatory
      abdominal aortic aneurysm. Thoracic aortic lesions are often associated with
      aortitis in several divergent etiologies. Thus, this study was performed to
      review thoracic aortic lesions from the aspect of IgG4-SD and to elucidate the
      clinicopathologic characteristics of this subgroup in the thoracic aorta.
      METHODS: The study comprised 125 patients, including 71 with thoracic aortic
      aneurysm (TAA), 44 with aortic dissection, 7 with Takayasu aortitis, and 3 with
      infectious aortitis. IgG4-SD was identified by diffuse infiltration of numerous
      IgG4-positive plasmacytes by immunohistochemical examinations. Clinicopathologic
      features were compared between IgG4-related and IgG4-unrelated lesions. RESULTS:
      Among the 125 patients, IgG4-SD was found in 5 patients with TAA but was not
      detected in the other subgroups of thoracic aortic lesion. IgG4-related TAA
      included one case of lymphoplasmacytic aortitis, 1 case of inflammatory aneurysm,
      and three cases of atherosclerotic aneurysms. Patients with IgG4-related TAA
      showed clinicopathologic features similar to patients with IgG4-SD: male gender,
      old age, history of bronchial asthma and allergies, elevation of white blood cell
      counts, C-reactive protein levels, and IgG4 and IgE concentrations (in one
      patient); eosinophilic infiltration, obliterative phlebitis, lymph follicle
      formation, and perineural inflammation. In addition, compared with IgG4-unrelated
      TAA, IgG4-related TAA was characterized by clinically more frequency of
      involvement of the aortic arch (P = .002), saccular formation (P = .003), and
      fibrous adhesion to surrounding tissue (P < .001), and histopathologically
      thicker entire aortic wall and adventitia (P < .001 each). CONCLUSIONS: IgG4-SD
      is involved in 4% of all thoracic aortic lesions and uniformly presents in the
      form of an aneurysm with distinct histologic and clinicopathologic features. IgG4
      SD represents one, albeit rare, etiology of TAA, especially those originating in
      the aortic arch.

PMID- 20678884
TI  - Laparoscopic treatment of renal artery entrapment.
AB  - Renal artery entrapment by the diaphragmatic crus is a very infrequent cause of
      renovascular hypertension. We present the case of a young man who was assigned to
      our hospital with arterial hypertension and stenosis of the left renal artery.
      Extrinsic compression was diagnosed by duplex ultrasound and magnetic resonance
      angiography. We performed laparoscopic decompression using the transperitoneal
      retrorenal approach. Antihypertensive medication could be stopped thereafter and
      duplex ultrasound revealed a normal blood flow to the left renal artery. We
      therefore propose laparoscopic treatment of left renal artery entrapment as a
      minimally-invasive alternative to open surgery.

PMID- 20678883
TI  - Preparation and characterization of injectable fibrillar type I collagen and
      evaluation for pseudoaneurysm treatment in a pig model.
AB  - OBJECTIVE: Despite the efficacy of collagen in femoral artery pseudoaneurysm
      treatment, as reported in one patient study, its use has not yet gained wide
      acceptance in clinical practice. In this particular study, the collagen was not
      described in detail. To further investigate the potential of collagen
      preparations, we prepared and characterized highly purified injectable fibrillar
      type I collagen and evaluated its use for femoral artery pseudoaneurysm (PSA)
      treatment in vivo using a pig model. METHODS: Purified fibrillar type I collagen
      was characterized using electron microscopy. The effect of three different
      sterilization procedures, ie, hydrogen peroxide gas plasma (H2O2), ethylene oxide
      gas (EtO), and gamma irradiation, was studied on both SDS-PAGE and platelet
      aggregation. Different collagen injectables were prepared (3%, 4%, and 5%) and
      tested using an injection force test applying a 21-gauge needle. To evaluate the
      network characteristics of the injectable collagen, the collagen was suspended in
      phosphate buffered saline (PBS) at 37 degrees C and studied both macroscopically
      and electron microscopically. To determine whether the collagen induced
      hemostasis in vivo, a pig PSA model was used applying a 4% EtO sterilized
      collagen injectable, and evaluation by angiography and routine histology.
      RESULTS: Electron microscopy of the purified type I collagen revealed intact
      fibrils with a distinct striated pattern and a length<300 MUm. Both SDS-PAGE and
      platelet aggregation analysis of the sterilized collagen indicated no major
      differences between EtO and H2O2 sterilization, although gamma-irradiated
      collagen showed degradation products. Both 3% and 4% (w/v) collagen suspensions
      were acceptable with respect to the force used (<50 N). The 4% suspension was
      selected as the preferred injectable collagen, which formed a dense network under
      physiologic conditions. Testing the collagen in vivo (n=5), the angiograms
      revealed that the PSA partly or completely coagulated. Histology confirmed the
      network formation, which was surrounded by thrombus. CONCLUSIONS: Collagen
      injectables were prepared and EtO sterilized without major loss of structural
      integrity and platelet activity. In vivo, the injectable collagen formed a dense
      network and triggered (partial) local hemostasis. Although optimization is
      needed, an injectable collagen may be used as a therapeutic agent for femoral PSA
      treatment.

PMID- 20678885
TI  - Venous ulcer diagnosis, treatment, and prevention of recurrences.

PMID- 20678886
TI  - Images of god in relation to coping strategies of palliative cancer patients.
AB  - CONTEXT: Religious coping is important for end-of-life treatment preferences,
      advance care planning, adjustment to stress, and quality of life. The currently
      available religious coping instruments draw on a religious and spiritual
      background that presupposes a very specific image of God, namely God as someone
      who personally interacts with people. However, according to empirical research,
      people may have various images of God that may or may not exist simultaneously.
      It is unknown whether one's belief in a specific image of God is related to the
      way one copes with a life-threatening disease. OBJECTIVES: To examine the
      relation between adherence to a personal, a nonpersonal, and/or an unknowable
      image of God and coping strategies in a group of Dutch palliative cancer patients
      who were no longer receiving antitumor treatments. METHODS: In total, 68
      palliative care patients completed and returned the questionnaires on Images of
      God and the COPE-Easy. RESULTS: In the regression analysis, a nonpersonal image
      of God was a significant positive predictor for the coping strategies seeking
      advice and information (beta=0.339, P<0.01), seeking moral support (beta=0.262,
      P<0.05), and denial (beta=0.26, P<0.05), and a negative predictor for the coping
      strategy humor (beta=-0.483, P<0.01). A personal image of God was a significant
      positive predictor for the coping strategy turning to religion (beta=0.608,
      P<0.01). Age was the most important sociodemographic predictor for coping and had
      negative predictive value for seeking advice and information (beta=-0.268,
      P<0.05) and seeking moral support (beta=-0.247, P<0.05). CONCLUSION: A
      nonpersonal image of God is a more relevant predictor for different coping
      strategies in Dutch palliative cancer patients than a personal or an unknowable
      image of God.

PMID- 20678887
TI  - Palliative use of aminocaproic acid to control upper gastrointestinal bleeding.

PMID- 20678888
TI  - Central sleep apnea in cancer patients on opioids.

PMID- 20678890
TI  - Need for mechanistically focused research of global systemic interventions in
      palliative care.

PMID- 20678889
TI  - Fatigue in children with cancer at the end of life.
AB  - CONTEXT: Fatigue is a prevalent source of suffering in children with advanced
      cancer; yet, little is known about it. OBJECTIVES: This study aimed to describe
      fatigue experienced by children with advanced cancer and to identify the factors
      associated with suffering from fatigue and its treatment. METHODS: A
      retrospective cross-sectional study of 141 parents of children who died of cancer
      (response rate: 64%) was conducted in two tertiary-level U.S. pediatric
      hospitals. RESULTS: By parent report, 96% of children experienced fatigue in the
      last month of life. Nearly 50% experienced significant suffering from fatigue;
      this was associated with suffering from pain, dyspnea, anorexia, nausea/vomiting,
      diarrhea, anxiety, sadness, or fear (P<0.05), and with side effects from pain or
      dyspnea treatment (P<0.05). In multivariate analysis of symptom-related factors,
      suffering from nausea/vomiting (odds ratio [OR]=3.93, 95% confidence interval
      [CI]=1.23-12.61, P=0.02); anorexia (OR=7.52, 95% CI=1.87-30.25, P=0.005); and
      fear (OR=5.13, 95% CI=2.03-12.96, P <= 0.001) remained independently associated
      with fatigue. Children suffering from fatigue had primary oncologists with fewer
      years' experience than children who did not suffer from fatigue (mean=7.7 years,
      standard deviation [SD]=4.9 vs. mean of 9.9 years, SD=6.0, P=0.02). Among
      children with fatigue, 17 of 129 (13%) received fatigue-directed treatment, which
      was successful in 3 of 12 (25%). Children experiencing side effects from dyspnea
      or pain treatment were more likely to be treated for fatigue (relative risk=1.25,
      95% CI=1.06-1.47, P=0.009). CONCLUSION: Fatigue is a common source of suffering
      in children with cancer at the end of life. Palliation of this symptom is rarely
      successful. Increased attention to factors associated with fatigue and effective
      interventions to ameliorate fatigue are needed.

PMID- 20678891
TI  - Persistent pain in survivors of torture: a cohort study.
AB  - CONTEXT: Refugee survivors of torture in the United Kingdom have multiple
      problems, of which pain may be underrecognized, given the high prevalence
      recorded in similar populations in Denmark. OBJECTIVES: To establish in a UK
      sample the prevalence of persistent pain and to investigate associations between
      specific pains and torture methods. METHODS: A cohort of a random 20% sample
      attending a specialist UK center for survivors of torture in 2005 was taken. All
      complaints of pain recorded at initial interview were categorized for body site
      and putative pain mechanism. These were compared with the database of personal
      variables and data on torture using odds ratios (ORs) and exact probability.
      RESULTS: Of 115 men and 63 women, with mean age of 30 years, 78% reported
      persistent multiple pains, mainly in the head and low back. They had experienced
      a median of six torture methods. There was a clear association between female
      abdominal/pelvic/genital pain and rape/sexual assault (17 of 34 vs. zero of 17:
      exact P<0.001) and between male anal pain and rape (two of nine vs. two of 77:
      OR=6.00; 95% confidence interval=1.79-20). Tests of foot/leg pain with falaka and
      shoulder pain with suspension did not show expected associations. CONCLUSION: A
      significant relationship emerged between torture and report of persistent pain at
      a high prevalence. Findings do not support the widespread clinical assumption
      that complaint of persistent pain after torture is predominantly a manifestation
      of psychological distress. Rather, complaints of pain in torture survivors should
      be assessed and treated in relation to physical trauma.

PMID- 20678892
TI  - Reducing the pain of nasogastric tube intubation with nebulized and atomized
      lidocaine: a systematic review and meta-analysis.
AB  - Nasogastric tube (NGT) intubations occur frequently in clinical practice and can
      be a painful procedure for patients. A systematic review of current knowledge
      concerning the use of nebulized lidocaine to reduce the pain of NGT insertion was
      conducted in order to develop evidence-based guidelines. In addition, a meta
      analysis of appropriate randomized controlled trials (RCTs) was performed. The
      databases included PubMed (1996-2009), ProQuest (1982-2009), CINAHL (1982-2009),
      and the Cochrane Central Register of Controlled Trials (2009), and reference
      lists of articles. Experts in this field also were contacted. Two investigators
      selected the research based on inclusion criteria and reviewed each study's
      quality according to the Jadad scale. Five RCTs with 212 subjects were
      identified. A total of 113 (58%) subjects were women. The mean age of treatment
      and control groups was 59.6 and 55 years, respectively. The countries of studies
      were the United States, United Kingdom, Australia, Canada, and Thailand. In the
      treatment groups, the use of lidocaine concentration was 4% and 10%. The pooled
      effect size was 0.423 (95% confidence interval: 0.204-0.880; Z=-2.301; P=0.021),
      indicating that the use of nebulized lidocaine before NGT insertion can decrease
      pain by 57.7%. There is insufficient evidence to recommend the dosage,
      concentration, or delivery method. Further research is needed to articulate a
      comprehensive clinical guideline.

PMID- 20678893
TI  - Contribution of a heating element to topical anesthesia patch efficacy prior to
      vascular access: results from two randomized, double-blind studies.
AB  - CONTEXT: Pain associated with superficial procedures, including intravenous (IV)
      access procedures, should be prevented when possible, especially in children.
      OBJECTIVES: To evaluate a topical local anesthetic patch containing lidocaine 70
      mg/tetracaine 70 mg with a heating element designed to warm the skin and
      facilitate rapid delivery of local anesthetics into the skin. The pilot study was
      designed to provide data to inform the design of the definitive study to evaluate
      the impact of controlled heat on the efficacy of the lidocaine/tetracaine patch
      (patch) when applied before IV cannulation. METHODS: Subjects in the pilot study
      were randomized to eight groups that varied by heated vs. unheated patch, 20 vs.
      30 minute application, and 16 vs. 18 G catheter. Subjects in the definitive study
      were randomized in a double-blind manner to receive either the heated or unheated
      patch, 20 minutes before vascular access, using a 16 G catheter in the
      antecubital space of the arm. In both studies, the primary efficacy measure was
      subject-reported pain intensity using a visual analog scale. RESULTS: Pilot
      study: Subjects who received the heated patch (n=43) vs. the unheated patch
      (n=37) had lower mean pain intensity scores (14.7 vs. 23.5mm, P=0.04). Pain
      intensity scores did not differ significantly by application time, but the
      difference between the 16 and 18 G catheter groups approached statistical
      significance (22.8 vs. 14.9 mm, P=0.05). Definitive study: Mean pain intensity
      scores for the heated patch group (n=124) vs. the unheated patch group (n=126)
      were 14.2 and 20.5mm, respectively (P=0.006). CONCLUSION: Heated patches provided
      significantly better pain relief compared with unheated patches. All the subjects
      tolerated the patches well, with few adverse effects.

PMID- 20678894
TI  - Parents' perceptions of their children's cancer-related symptoms during
      treatment: a prospective, longitudinal study.
AB  - CONTEXT: This article describes a comprehensive assessment of treatment-related
      symptoms in children aged 0-18 years undergoing cancer treatment from the
      perspective of their parents. OBJECTIVES: The aim was to describe which symptoms
      that, according to parents, cause most problems for children receiving cancer
      treatment and to explore whether there is a relationship between parents' ratings
      of their children's symptoms and their own post-traumatic stress at one week
      (T1), two months (T2), and four months (T3) after a child's cancer diagnosis.
      METHODS: In total, 214 parents (107 mothers and 107 fathers) of 115 children
      answered a modified version of the Memorial Symptom Assessment Scale 10-18 and
      the PTSD Checklist Civilian Version over the telephone at T1-T3. RESULTS:
      According to parents, the following symptom areas cause the most problems for
      children undergoing cancer treatment: emotional distress, fatigue, nutrition, and
      pain. Pain is the most problematic area. The prevalence of most symptoms and the
      symptom burden decreases over time. Parents' ratings of their children's symptom
      burden and their own emotional distress, and mothers' and fathers' ratings of
      their child's symptom burden, are associated. Parents of adolescents report a
      greater symptom burden for their child than the parents of the youngest children.
      CONCLUSION: The opinions of both the patient and the parent are important in
      pediatrics. The results of this study can be used to guide health care
      professionals within pediatric oncology in their discussions of cancer
      treatment's adverse effects with patients and families. Not only the expectations
      and potential interventions but also the sources of worry should be discussed.

PMID- 20678895
TI  - The deliverability, acceptability, and perceived effect of the Macmillan approach
      to weight loss and eating difficulties: a phase II, cluster-randomized,
      exploratory trial of a psychosocial intervention for weight- and eating-related
      distress in people with advanced cancer.
AB  - CONTEXT: Up to 80% of people with cancer will develop weight loss and anorexia
      during the advanced stages of the disease. The Macmillan Weight and Eating
      Studies (2000-2009) have used the Medical Research Council complex interventions
      framework to develop the first psychosocial intervention for weight- and eating
      related distress (WRD and ERD) in people with advanced cancer and their carers:
      The Macmillan Approach to Weight and Eating (MAWE). OBJECTIVES: This article
      reports the findings of a Phase II trial of MAWE that investigated its
      deliverability, acceptability, and patient-perceived effect on WRD and ERD.
      METHODS: The Phase II trial, conducted in 2006-2007, was of cluster-randomized
      design, with two community palliative care teams randomized to different arms. It
      used mixed methods to compare an intervention group (n=25), the MAWE group, which
      was supported by MAWE-trained clinical nurse specialists, with a group that
      received usual care (n=25), the control group. RESULTS: MAWE was deliverable in
      clinical practice and acceptable to patients. Unplanned exposure of the MAWE
      group to the intervention before an initial measure of WRD and ERD proved
      problematic to the trial process. Despite this, quantitative and qualitative
      analyses indicate that MAWE does not exacerbate WRD and ERD and may help patients
      with advanced cancer live with the weight loss and anorexia that are the symptoms
      of cancer cachexia syndrome. CONCLUSION: A follow-on randomized controlled trial
      of MAWE is warranted but should be of a revised design.

PMID- 20678896
TI  - Pain prevalence, experiences, and self-care management strategies among the
      community-dwelling elderly in Taiwan.
AB  - The purpose of this study was to explore pain prevalence, experiences, and self
      care management strategies among community-dwelling elderly in Taiwan. A
      convenience sample of elderly persons (n=1054) was recruited from outpatient
      clinics of two hospitals in northern Taiwan. Participants' pain prevalence was
      50.0%, and the average number of pain sites was 3.9 (standard deviation
      [SD]=5.8). Knees were the most commonly described pain site, but the most painful
      site was the spinal cord area. The mean pain intensity was 3.1 (SD=1.8) and pain
      interference was 2.8 (SD=2.1). Most participants took prescribed medications to
      deal with pain; doctors were the main information source for this self-care
      strategy. Although participants reported using various self-care pain management
      strategies, most still reported moderate-to-severe worst pain. Moreover, our
      participants identified far fewer self-care strategies than U.S. elders with
      chronic pain. These findings suggest that community-dwelling elders in Taiwan
      know little about managing pain symptoms or ascribe a different meaning to pain
      than their U.S. counterparts. Because health care providers play an important
      role in helping the elderly to manage pain, the authors recommend training health
      care providers about Taiwanese elders' perceptions of pain, to perform regular
      pain assessments, and provide current knowledge about pain assessment and pain
      management strategies.

PMID- 20678897
TI  - Narrative empathy and how dealing with stories helps: creating a space for
      empathy in culturally diverse care settings.

PMID- 20678898
TI  - Development and initial validation of the Environmental Restriction Questionnaire
      (ERQ).
AB  - The purpose of this manuscript was to develop and test the psychometric
      properties of the Environmental Restriction Questionnaire (ERQ) a parent-reported
      questionnaire for measuring perceived environmental restrictions for young
      children participation. Reliability and homogeneity were tested by Cronbach's
      alpha and inter-item correlations. Construct validity was computed by factor
      analysis and known group differences analysis. Convergent and divergent
      validities were calculated by correlation with the Children Participation
      Questionnaire (CPQ). Participants were 290 children and their parent. Seventy
      five children who were referred to occupational therapy evaluation as consequence
      of moderate developmental disabilities and 215 children without any disability
      (mean age +/- standard deviation for total sample, 5 y, 3 mo +/- .65 y; range, 3
      y, 11 mo to 6 y, 10 mo). The ERQ has good internal reliability. Cronbach's alpha
      for the ERQ measures ranged between .75 and .91, indicating adequate homogeneity.
      Factor analysis yielded three factors that explained almost 48% of the total
      variance. Significant differences were found between known groups. Convergent and
      divergent validity were supported by various correlations with the Children
      Participation Questionnaire (CPQ). The ERQ has demonstrated good psychometric
      properties and can be used as a reliable and valid measure to assess perceived
      environmental restriction at the age of 4-6 y.

PMID- 20678899
TI  - The new polyomavirus (MCPyV) does not affect the clinical course in MCCs.
AB  - Since 2008, a new polyomavirus (MCPyV) in Merkel cell carcinomas (MCC) has been
      described, but little is known about its impact on the clinical course. The
      purpose of this study was to determine the presence of MCPyV in a large sample
      and to correlate the results with the clinical course of the disease. 59 samples
      from 44 patients were analysed for the presence of MCPyV using the primers LT3,
      VP1 and LT1. The clinical records of these patients were evaluated and correlated
      with the presence of MCPyV. 58% of specimens were positive for MCPyV. Of these,
      LT3 was positive in 53%, VP1 in 37% and LT1 in 10%. 57% of primary tumours and
      53% of metastases were positive for LT3; the numbers for VP1 and LT1 were lower.
      There was no correlation between the detection of MCPyV in the primary tumour and
      the appearance of metastases. The survival time was statistically independent
      from the presence of MCPyV. There is a striking occurrence of MCPyV in MCC, but
      whether it affects the clinical course remains unclear.

PMID- 20678900
TI  - Effects of HMG-CoA reductase inhibitors on continuous post-inflammatory vascular
      remodeling late after Kawasaki disease.
AB  - BACKGROUND: In Kawasaki disease (KD), it has been clinically and experimentally
      reported that post-inflammatory vascular remodeling would induce the development
      of arteriosclerosis or early onset of atherosclerosis in the future. The effects
      of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors on
      continuous vascular remodeling late after Kawasaki disease were clinically
      evaluated. PATIENTS AND METHODS: We enrolled and treated a total of 11 KD
      patients (age range, 7-25 years) with fluvastatin (0.5-0.7 mg/kg/day) for 12
      months. All of them had significant coronary aneurysmal or stenotic lesions and
      more than 3 of the following 5 abnormal findings: reduced %flow-mediated
      dilatation (%FMD), reduced urinary NOx, elevated high-sensitivity C-reactive
      protein (hs-CRP), reduced urinary 8-isoprostane, and elevated brachial-ankle
      pulse wave velocity (baPWV; control, <=1400 cm/s). RESULTS: A statistically
      significant improvement was observed in each biomarker after fluvastatin
      treatment: %FMD, from 9.29% (3.41)% to 10.55% (3.27)% (p=0.003) after 3 months;
      NOx/creatinine (cre), from 1.16 (0.54) umol/mg cre to 1.30 (0.50) umol/mg cre
      (p=0.038) after 12 months; baPWV, from 1175.4 (277.3) cm/s to 1031.8 (155.6) cm/s
      (p=0.009) after 3 months; hs-CRP, from 0.073 (0.035) mg/dl to 0.028 (0.014) mg/dl
      (p=0.0002) after 3 months; and 8-iso/cre, from 751.8 (241.8) pg/mg cre to 660.0
      (198.5) pg/mg cre (p=0.018) after 3 months. No adverse events were clinically
      observed in the patients. CONCLUSIONS: The results of this study suggested that
      HMG-CoA reductase inhibitors are useful as an alternative therapeutic strategy
      for stabilizing continuous post-inflammatory vascular remodeling that results in
      the development of arteriosclerosis late after KD or early onset of
      atherosclerosis in the future.

PMID- 20678901
TI  - Brivaracetam does not alter spatial learning and memory in both normal and
      amygdala-kindled rats.
AB  - Several antiepileptic drugs (AEDs) may induce memory deficits when tested in
      preclinical models at doses that exert significant protection against seizures.
      Brivaracetam (BRV) is a novel high-affinity SV2A ligand also displaying
      inhibitory activity at neuronal voltage-gated sodium channels. In the present
      study we have investigated the effects of BRV, at doses that exerted marked
      anticonvulsant effects in kindled rats, upon cognitive functioning and memory in
      both normal and amygdala-kindled rats using place learning version of Morris
      water maze. In addition the effect of BRV on long-term potentiation (LTP) in rat
      hippocampal slices has been investigated. BRV (2.1, 6.8 or 21.0mg/kg i.p.) was
      injected daily, 60min before each session. Results indicated that in both normal
      and amygdala-kindled rats BRV did not alter the latency to find the hidden
      platform or swimming speed during the four consecutive days of learning.
      Similarly, the time spent in the target quadrant, used as a further independent
      index of spatial memory, was not modified by BRV treatment. Likewise, BRV did not
      affect the LTP induction in CA1 hippocampal region when tested at 3-30microM
      concentration range, which had been demonstrated to significantly reduce
      epileptiform activity in slice models. Based on the results of the present study
      it can be expected that BRV will not have detrimental effects on hippocampal
      dependent cognitive functions in patients with epilepsy.

PMID- 20678902
TI  - Antimycobacterial activity of UDP-galactopyranose mutase inhibitors.
AB  - The galactofuran region of the mycobacterial cell wall consists of alternating 5-
      and 6-linked beta-d-galactofuranose (beta-D-Galf) residues, essential for
      viability. UDP-galactofuranose (UDP-Galf), the donor for Galf, is synthesised
      from UDP-galactopyranose (UDP-Galp) by the enzyme UDP-galactopyranose mutase
      (UGM), which is not found in humans, rendering it a therapeutic target. The in
      vitro properties, i.e. enzymatic activity, antimycobacterial activity, cellular
      toxicity, activity in mycobacterial-infected macrophages and activity against non
      replicating persistent mycobacteria, of (4-chlorophenyl)-[1-(4-chlorophenyl)-3
      hydroxy-5-methyl-1H-pyrazol-4-yl]-methanone and 3-(4-iodophenyl)-2-[4-(3,4
      dichlorophenyl)-thiazol-2-ylamino]-propionic acid were studied. The former
      compound, a pyrazole, was an inhibitor of UGM from Mycobacterium tuberculosis and
      Klebsiella pneumoniae and was effective against Mycobacterium smegmatis,
      Mycobacterium bovis BCG and M. tuberculosis but ineffective against other
      bacterial strains tested. This compound showed potency against mycobacteria in
      infected macrophages but exhibited moderate cellular toxicity and was ineffective
      against non-replicating persistent mycobacteria. This is the first report of a
      compound both with UGM inhibitory properties and broad antimycobacterial
      activities. The latter compound, an aminothiazole, was active against UGM from K.
      pneumoniae and M. tuberculosis but was ineffective against M. bovis BCG or M.
      tuberculosis as well as demonstrating higher cellular toxicity. These data
      validate the choice of UGM as a target for active antimycobacterial therapy and
      confirm the pyrazole compound as a viable lead candidate.

PMID- 20678903
TI  - Self-assembly behavior of peptide amphiphiles (PAs) with different length of
      hydrophobic alkyl tails.
AB  - Amphiphilic peptide and their derivatives, with distinguished advantages over
      conventional materials, have received extensively research interesting recently.
      In this work, four peptide amphiphiles (PAs1-4) with different length of
      hydrophobic alkyl tails (C9 for PA1, C11 for PA2, C13 for PA3, and C15 for PA4)
      were fabricated and their self-assembly behaviors in aqueous medium at different
      pHs were investigated systematically. It was found that all the peptide
      amphiphiles can self-assemble in water at a neutral pH of 7 to form tightly
      packed nanofibers with a beta-sheet conformation. When altering the solution
      environment to basic medium (pH 11), due to the strong hydrophobic interaction of
      long alkyl tails in PA3 and PA4, the fibrous nanostructure self-assembled from
      PA3 and PA4 was not destroyed. However, the nanofibers self-assembled from PA1 in
      which the length of alkyl tail was relatively short converted into loose
      spherical micelles with a beta-sheet conformation. Due to the moderate length of
      alkyl tail in PA2, both nanofibers and micelles can be formed via the self
      assembly of PA2 when increasing the pH of the self-assembling system.

PMID- 20678904
TI  - Short term dietary sodium restriction decreases HDL cholesterol, apolipoprotein A
      I and high molecular weight adiponectin in healthy young men: relationships with
      renal hemodynamics and RAAS activation.
AB  - BACKGROUND AND AIMS: We aimed to determine the effect of short-term dietary
      sodium restriction on plasma total cholesterol, LDL-C, HDL-C, triglycerides,
      apolipoprotein (apo) A-I, apo B and high molecular weight (HMW) adiponectin in
      non-obese, normotensive young men. Glomerular filtration rate (GFR), effective
      renal plasma flow (ERPF), plasma renin activity (PRA) and aldosterone were also
      measured. METHODS AND RESULTS: Sixty-five men, aged 23 +/- 7 years, were randomly
      studied on a high sodium intake (HS, 228 +/- 77 mmol Na+/24 h) and a low sodium
      intake (LS, 36 +/- 27 mmol Na+/24 h), each period lasting 1 week. LS decreased
      GFR and ERPF and increased PRA and aldosterone (p < 0.0001 for all). LS also
      induced a decrease in HDL-C (3.8 +/- 10.8%), apo A-I (3.7 +/- 6.5%) and HMW
      adiponectin (13.6 +/- 40.5%) (p < 0.05 for all), but plasma total cholesterol,
      LDL-C, triglycerides and apo B did not significantly change. The changes in HDL-C
      and apo A-I were correlated negatively to the changes in effective renal plasma
      flow (p < 0.05), whereas the changes in HMW adiponectin were correlated
      negatively to the changes in PRA and aldosterone (p < 0.05 for both). CONCLUSION:
      Short term sodium restriction modestly decreases HDL-C, apo A-I and HMW
      adiponectin in healthy men. Changes in GFR and ERPF and in the renin-angiotensin
      aldosterone system as induced by LS may be involved in these responses.

PMID- 20678905
TI  - Relation of dietary and lifestyle traits to difference in serum leptin of
      Japanese in Japan and Hawaii: the INTERLIPID study.
AB  - BACKGROUND AND AIMS: Previously, we found significantly higher serum leptin in
      Japanese-Americans in Hawaii than Japanese in Japan. We investigated whether
      differences in dietary and other lifestyle factors explain higher serum leptin
      concentrations in Japanese living a Western lifestyle in Hawaii compared with
      Japanese in Japan. METHODS AND RESULTS: Serum leptin and nutrient intakes were
      examined by standardized methods in men and women ages 40-59 years from two
      population samples, one Japanese-American in Hawaii (88 men, 94 women), the other
      Japanese in central Japan (123 men, 111 women). Multiple linear regression models
      were used to assess role of dietary and other lifestyle traits in accounting for
      serum leptin difference between Hawaii and Japan. Mean leptin was significantly
      higher in Hawaii than Japan (7.2 +/- 6.8 vs 3.7 +/- 2.3 ng/ml in men, P < 0.0001;
      12.8 +/- 6.6 vs 8.5 +/- 5.0 in women <0.0001). In men, higher BMI in Hawaii
      explained over 90% of the difference in serum leptin; in women, only 47%. In
      multiple linear regression analyses in women, further adjustment for physical
      activity and dietary factors--alcohol, dietary fiber, iron--produced a further
      reduction in the coefficient for the difference, total reduction 70.7%; P-value
      for the Hawaii-Japan difference became 0.126. CONCLUSION: The significantly
      higher mean leptin concentration in Hawaii than Japan may be attributable largely
      to differences in BMI. Differences in nutrient intake in the two samples were
      associated with only modest relationship to the leptin difference.

PMID- 20678906
TI  - Effects of simvastatin on carotenoid status in plasma.
AB  - BACKGROUND AND AIMS: Carotenoids are potent antioxidants mainly transported in
      the low density lipoprotein (LDL) fraction. They may also influence the immune
      response and inverse associations with inflammatory markers have been reported.
      We investigated whether simvastatin, by exerting both lipid-lowering and anti
      inflammatory effects, altered the carotenoid status in plasma. METHODS AND
      RESULTS: A randomized, double-blind, placebo-controlled study design was applied.
      Eighty volunteers with mild to moderate hypercholesterolemia received either
      simvastatin 40 mg or placebo for 6 weeks. Lipids, oxidized LDL (ox-LDL), C
      reactive protein (CRP), interleukin (IL)-6, oxygenated carotenoids (lutein,
      zeaxanthin, beta-cryptoxanthin) and hydrocarbon carotenoids (alpha-carotene, beta
      carotene, lycopene) were measured in plasma. Simvastatin use was associated with
      significant reductions in total cholesterol, LDL, ox-LDL and CRP. Simvastatin
      therapy also resulted in reduced plasma levels of both oxygenated and hydrocarbon
      carotenoids. However, when adjusted for lipids, all carotenoids except beta
      cryptoxanthin showed significant increases after simvastatin therapy. Both crude
      and lipid-adjusted carotenoids were inversely correlated with CRP and IL-6 in
      plasma but the change in carotenoid status during simvastatin therapy was not
      specifically related to any changes in inflammatory markers. CONCLUSIONS: To
      summarize, the change in carotenoid status during simvastatin therapy was mainly
      attributed to the lowering of cholesterol and not to the suppression of
      inflammatory activity. After adjustment for lipids, the levels of lutein,
      lycopene, alpha-carotene and beta-carotene were significantly increased by
      simvastatin suggesting an increased ratio of carotenoids per particle.

PMID- 20678907
TI  - Bilberry anthocyanin-rich extract alters expression of genes related to
      atherosclerosis development in aorta of apo E-deficient mice.
AB  - Intake of anthocyanin-rich foods has been associated with a reduced risk of
      cardiovascular diseases. We recently reported that a nutritional supplementation
      with a bilberry anthocyanin-rich extract (BE) attenuates atherosclerotic lesion
      development in apolipoprotein E-deficient (apoE-/-) mice. However, the
      mechanism(s) of their preventive action are not completely understood.
      Anthocyanins may alter mRNA levels of genes related to atherosclerosis in
      cultured macrophages and endothelial cells, but in vivo studies remain scarce.
      The aim of the present study was to explore the in vivo mechanisms of action of
      the same bilberry extract, administered by supplementation at a nutritional
      level, in the aorta of apo E-/- mice using a global transcriptomic approach. This
      study focused on the early stage of atherosclerosis development for better
      assessment of BE action on initiation mechanisms of this pathology. After a two
      week period, plasma lipid and antioxidant capacity were evaluated and the global
      genomic analysis was carried out using pangenomic microarrays. BE supplementation
      significantly improved hypercholesterolemia whereas the plasmatic antioxidant
      status remained unchanged. Nutrigenomic analysis identified 1261 genes which
      expression was modulated by BE in the aorta. Bioinformatic analysis revealed that
      these genes are implicated in different cellular processes such as oxidative
      stress, inflammation, transendothelial migration and angiogenesis, processes
      associated with atherosclerosis development/protection. Some of the most
      significantly down-regulated genes included genes coding for AOX1, CYP2E1 or
      TXNIP implicated in the regulation of oxidative stress, JAM-A coding for adhesion
      molecules or VEGFR2 implicate in regulation of angiogenesis. Other genes were up
      regulated, such as CRB3, CLDN14 or CDH4 potentially associated with increased
      cell-cell adhesion and decreased paracellular permeability. These results provide
      a global integrated view of the mechanisms involved in the preventive action of
      bilberry anthocyanin-rich extract against atherosclerosis.

PMID- 20678908
TI  - Antibacterial and ulcer healing effects of organoselenium compounds in naproxen
      induced and Helicobacter pylori infected Wistar rat model.
AB  - Aim of the present study was to evaluate in vitro toxicity and in vivo
      antibacterial, anti-inflammatory, antiulcer, and antioxidant activities of two
      organoselenium compounds, selenocystine (SeCys) and ebselen (Ebs). The study was
      conducted in experimentally induced ulcers in rodent model infected with
      Helicobacter pylori (H. pylori). In vitro toxicological studies on normal splenic
      lymphocytes revealed that SeCys and Ebs were non-toxic to the cells even at 100
      MUM concentration. Antibacterial activity was observed at 500 MUg/mL
      concentration of either of the compounds against H. pylori. In vivo studies after
      treatment with SeCys and Ebs (500 MUg/kg/day) resulted in significant reduction
      in ROS production and inhibition of lipid peroxidation in gastric tissue. The
      antioxidant and anti-inflammatory activities of both the compounds were also
      confirmed by their ability to lower GSH reduction, to induce the expression of
      antioxidant genes such as GPx-4, and MnSOD and to suppress inflammatory genes
      namely COX-2, TNF-alpha and TGF-beta. In addition, the immunomodulatory activity
      of both the compounds was evident by enhance of the CD4 levels and maintenance of
      the IgG, IL-6 and IL-10 levels. Persistent treatment (500 MUg/kg, for 28 days)
      with both the compounds showed considerable (p<0.05) ulcer healing property
      supporting its role in gastro protection. In conclusion, the results of our study
      suggest that both SeCys and Ebs possess broad spectrum of activities without any
      potential toxicity.

PMID- 20678909
TI  - Perfluorinated carboxylic acids inhibit cyclooxygenase pathway more potently than
      12-lipoxygenase pathway in rat platelets.
AB  - Two perfluorinated carboxylic acids (PFCAs), pentadecafluorooctanoic acid (PDFOA)
      and heptadecafluorononanoic acid (HDFNA), were investigated for potential
      modulatory effects on the cyclooxygenase (COX) and 12-lipoxygenase (LOX)
      metabolisms in rat platelets. Both PDFOA and HDFNA dose-dependently inhibited the
      formation of a COX metabolite, 12-HHT, without any effect on that of a LOX
      metabolite, 12-HETE, at concentrations ranging from 10 to 100MUM. These two PFCAs
      up to 100MUM did not affect platelet membrane integrity, and COX-1 and -2 protein
      expression levels in Caco-2 cells. These results suggest that PDFOA and HDFNA
      have the potential to modify platelet function by inhibiting the COX pathway at
      activity level, but not at protein level.

PMID- 20678910
TI  - Regulated protein kinases and phosphatases in cell cycle decisions.
AB  - Many aspects of cell physiology are controlled by protein kinases and
      phosphatases, which together determine the phosphorylation state of targeted
      substrates. Some of these target proteins are themselves kinases or phosphatases
      or other components of a regulatory network characterized by feedback and feed
      forward loops. In this review we describe some common regulatory motifs involving
      kinases, phosphatases, and their substrates, focusing particularly on bistable
      switches involved in cellular decision processes. These general principles are
      applied to cell cycle transitions, with special emphasis on the roles of
      regulated phosphatases in orchestrating progression from one phase to the next of
      the DNA replication-division cycle.

PMID- 20678911
TI  - Assisted morphogenesis: glial control of dendrite shapes.
AB  - Neurons display a myriad of dendritic architectures, reflecting their diverse
      roles in information processing and transduction in the nervous system. Recent
      findings suggest that neuronal signals may not account for all aspects of
      dendrite morphogenesis. Observations from C. elegans and other organisms suggest
      that glial cells can affect dendrite length and guidance, as well as localization
      and shapes of dendritic receptive structures, such as dendritic spines and
      sensory cilia. Thus, besides direct roles in controlling neuronal activity, glia
      contribute to neuron function by ensuring that neurons attain their proper
      shapes.

PMID- 20678912
TI  - Resolving cell-cell junctions: lumen formation in blood vessels.
AB  - Formation of a patent vascular lumen is essential for the transport of oxygen,
      nutrients and waste products to and from tissues. No matter whether the blood
      vessel arises from vasculogenesis or angiogenesis, endothelial cells (EC) first
      have to form a cord, which subsequently lumenizes, in order to generate a
      functional vessel. During these processes, cellular junctions rearrange between
      adjacent ECs and are involved in EC polarization as a prerequisite for lumen
      formation. Here we review the role of EC junctions in vascular lumen formation
      within different vascular beds.

PMID- 20678913
TI  - Electrochemical growth of Acidithiobacillus ferrooxidans on a graphite electrode
      for obtaining a biocathode for direct electrocatalytic reduction of oxygen.
AB  - An aspect in microbial fuel cell research that is currently of great interest is
      the development of bacterial cathodes. Bacterial cathodes that catalyze oxygen
      reduction to water at low pH have the advantage of overcoming the kinetic
      limitations due to the requirement of 4 protons per molecule reduced. In this
      work we have studied the performance of a biocathode using as electrocatalyst an
      acidophile microorganism: Acidithiobacillus ferrooxidans. Growth of the
      microorganism directly on the electrode took place using an applied voltage of 0
      V vs. SCE as the only energy source and without adding redox mediators to the
      solution. Current densities of up to 5 A m(-2) were measured for O2 reduction in
      the At. ferrooxidans cathode at pH 2.0 and the electrocatalytic wave was shifted
      300 mV to higher potential compared to the control graphite electrodes without
      the bacterium.

PMID- 20678914
TI  - Impedimetric immunosensor based on SWCNT-COOH modified gold microelectrodes for
      label-free detection of deep venous thrombosis biomarker.
AB  - Measurement of D-dimer has subsequently become an essential element in the
      diagnostics of deep vein thrombosis and pulmonary embolism; in this context
      microelectrodes with an area of 9*10(-4) cm(2) were used to develop impedimetric
      immunosensor for detecting deep venous thrombosis biomarker (D-dimer). The
      biosensor is based on functionalized carbon nanotubes (SWCNT-COOH) where the
      antibody (anti-D-dimer) was immobilized by covalent binding. The electrical
      properties and the morphology of the biolayer were characterized by
      electrochemical impedance spectroscopy (EIS), cyclic voltammetry and atomic force
      spectroscopy (AFM). Impedimetric microimmunosensor allows to obtain sensitivity
      of 40.1 kOmega MUM(-1) and detection limit of 0.1 pg/mL (0.53 fM) with linear
      range from 0.1 pg/mL to 2 MUg/mL (0.53 fM to 0.01 MUM). We demonstrate that using
      carbon nanotubes and microelectrodes, high sensitivity and dynamic range were
      obtained. The biosensor exhibited a short response time of 10 min. Moreover, the
      studied immunosensor exhibits good reproducibility (R.S.D. 8.2%, n=4).

PMID- 20678915
TI  - Nanoparticles-based strategies for DNA, protein and cell sensors.
AB  - The need for novel biosensing systems has increased enormously in the last few
      years. In this context nanoparticles with special optical and electrochemical
      properties are bringing significant advantages in fields such as clinical
      analysis, environmental monitoring, food and safety/security control. Biosensor
      technology represents an interesting alternative for the development of
      efficient, fast, low-cost and user-friendly biosensing devices. Between different
      biosensing alternatives the nanotechnology and nanomaterial oriented biosensors
      represent very attractive and cost-efficient tools for real sample applications.
      The developed devices are based on the use of various platforms which allows
      their future applications and extension in several fields. Optical detection
      alternatives based on light absorption and scattering, surface plasmon resonance
      enhancement, fluorescence (including its quenching strategies) between other
      methods will be discussed. In addition, a special emphasis on electrical methods
      (electromechanical, stripping analysis, potentiometric etc.) that use
      nanoparticles as tracers for biomolecules detection will be given. In most of the
      examples nanoparticle-based biosensing systems are being offered as excellent
      screening and advantageous alternatives to existing conventional
      strategies/assays and the corresponding equipment.

PMID- 20678916
TI  - Effects of protein inter-layers on cell-diamond FET characteristics.
AB  - Diamond is recognized as an attractive material for merging solid-state and
      biological systems. The advantage of diamond field-effect transistors (FET) is
      that they are chemically resistant, bio-compatible, and can operate without gate
      oxides. Solution-gated FETs based on H-terminated nanocrystalline diamond films
      exhibiting surface conductivity are employed here for studying effects of fetal
      bovine serum (FBS) proteins and osteoblastic SAOS-2 cells on diamond electronic
      properties. FBS proteins adsorbed on the diamond FETs permanently decrease
      diamond conductivity as reflected by the -45 mV shift of the FET transfer
      characteristics. Cell cultivation for 2 days results in a further shift by
      another -78 mV. We attribute it to a change of diamond material properties rather
      than purely to the field-effect. Increase in gate leakage currents (by a factor
      of 4) indicates that the FBS proteins also decrease the diamond-electrolyte
      electronic barrier induced by C-H surface dipoles. We propose a model where the
      proteins replace ions in the very vicinity of the H-terminated diamond surface.

PMID- 20678917
TI  - A generic surface chemistry for peptide microarrays implementation: application
      to the detection of anti-H3 antibody.
AB  - Peptide microarray can be implemented by immobilization of peptides on a solid
      support or by direct on-chip peptide synthesis (OCPS). In the first case, peptide
      primary sequences can be ensured prior to their immobilization but structural
      diversity is achieved at high cost in terms of reagents. In the second case, high
      diversity is achieved with low amount of reagents but the primary and secondary
      structures cannot be ascertained. In both cases, the immobilization step will
      influence the overall biological activity. We proposed a strategy where direct
      peptide on-chip synthesis and peptide immobilization are viewed as complementary
      approaches. In a first step, OCPS is envisioned for the screening and selection
      of biologically relevant peptides. In a second step, selected peptides would be
      synthesized on resin, qualified and immobilized for implementing microarrays
      (i.e. for diagnosis). A versatile surface chemistry for both OCPS and peptide
      immobilization was developed allowing for an identical physico-chemical
      environment for both implementation strategies. In the present report, a 16 mer
      peptide corresponding to the human histone H3 epitope was synthesized on an amino
      functionalized support. Surface stability (including upon deprotection steps) and
      peptide primary and secondary structures were assessed with Cy3-streptavidine
      conjugates and with immunoassays. Peptides, either on-chip synthesized or
      immobilized, exhibited a similar biological activity.

PMID- 20678918
TI  - Fluorescent molecularly imprinted polymer film binds glucose with a concomitant
      changes in fluorescence.
AB  - A fluorescent molecularly imprinted polymeric formulation capable of picking up
      glucose from aqueous media is reported. The fluorescence intensity of the polymer
      film was found to reduce proportionally with the concentration of glucose
      facilitating its use as a glucose sensing element. We used commercially available
      tear fluid to demonstrate the ability of the film to recognize glucose among
      other sugar molecules. Fluorescence was measured after equilibrating the film in
      tear fluid in the presence of a mixture of different sugars. We observed a
      reduction in fluorescence intensity due to the nonspecific binding of the sugars.
      The intensity remains the same even if we added additional quantities of the
      sugars. Interestingly, the fluorescence intensity of the film was found to
      decrease proportionally when varied concentrations of glucose was added
      indicating the ability of the film to recognize and bind glucose from a mixture
      of other sugars. Detectable changes in fluorescence intensity were observed with
      a concentration of 10 MUg/mL of glucose. The results show that the polymer film
      could be used for detecting glucose in aqueous fluids such as tear.

PMID- 20678919
TI  - Electrogenerated chemiluminescence biosensor for glucose based on poly(luminol
      aniline) nanowires composite modified electrode.
AB  - Poly(luminol-aniline) nanowires composite (PLANC) was synthesized on the surface
      of graphite electrode by electro-oxidizing the mixture of luminol with aniline in
      the H2SO4 acidic medium. The properties of the nanowires composite were
      characterized by transmission electron microscopy, electrogenerated
      chemiluminescence and electrochemical impedance spectroscopy. The investigating
      results showed that: firstly, while the luminol alone was electro-oxidized on the
      surface of the graphite electrode with the proposed synthetic method, only the
      polyluminol film was formed on electrode surface. However, while a suitable
      amount of the aniline was present in the luminol solution, the PLANC could be
      formed on the electrode surface and this PLANC presented better ECL properties
      for H2O2 compared with pure polyluminol film; secondly, since the PLANC modified
      electrode not only provided a larger surface area for higher glucose enzyme
      loading but also formed the nano-structured interface on the electrode surface to
      improve the analytical performances of the electrogenerated chemiluminescence
      (ECL) biosensor for glucose, the resulting ECL biosensor presented good response
      to glucose and a novel ECL biosensor for glucose was proposed.

PMID- 20678921
TI  - Molecularly imprinted polymeric microspheres for determination of bovine serum
      albumin based on flow injection chemiluminescence sensor.
AB  - A novel flow injection chemiluminescence (FI-CL) sensor for the determination of
      bovine serum albumin (BSA) using molecularly imprinted polymeric microspheres
      (MIPMs) as recognition element is reported. The BSA-MIPM was synthesized by
      suspension polymerization in toluene, using methacrylic acid (MAA) as functional
      monomer and ethylene glycol dimethacrylate (EGDMA) as cross-linker in the bovine
      serum albumin template molecule. Scanning electron microscope (SEM) was employed
      to characterize the surface morphology of the resultant imprinted microspheres.
      Molecular modeling was employed to simulate the possible recognition process of
      the MIPM. Then the synthesized BSA-MIPM was employed as recognition element by
      packing into flow cell to establish a novel FI-CL sensor. The chemiluminescence
      (CL) intensity was correlated linear with the concentration of BSA over the range
      of 1.0*10(-8) to 5.0*10(-6) g mL(-1) and the detection limit was 1.5*10(-9) g mL(
      1). The relative standard deviation (RSD) for the determination of 1.0*10(-7) g
      mL(-1) BSA was 1.4% (n=11). The sensor is reusable and has a great improvement in
      sensitivity and selectivity for CL analysis. As a result, the new MIPM-CL sensor
      had been successfully applied to the determination of BSA in milk samples.

PMID- 20678920
TI  - Layer-by-layer assembly of bi-protein/layered double hydroxide ultrathin film and
      its electrocatalytic behavior for catechol.
AB  - This paper reports the fabrication of a bi-protein/layered double hydroxide (LDH)
      ultrathin film in which hemoglobin (HB) and horseradish peroxidase (HRP)
      molecules were assembled alternately with LDH nanosheets via the layer-by-layer
      (LBL) deposition technique, and its electrocatalytic performances for oxidation
      of catechol were demonstrated. The results of XRD indicate that the HB-HRP/LDH
      ultrathin film possesses a long range stacking order in the normal direction of
      the substrate, with the two proteins accommodated in the LDH gallery respectively
      as monolayer arrangement. SEM images show that the film surface exhibits a
      continuous and uniform morphology, and AFM reveals the Root-Mean-Square (RMS)
      roughness of ~10.2 nm for the film. A stable direct electrochemical redox
      behavior of the proteins was successfully obtained for the HB-HRP/LDH film
      modified electrode. In addition, it exhibits remarkable electrocatalytic activity
      towards oxidation of catechol, based on the synergistic effect of the two
      proteins. The catechol biosensor in this work displays a wide linear response
      range (6-170 MUM, r=0.999), low detection limit (5 MUM), high sensitivity and
      good reproducibility.

PMID- 20678922
TI  - Neuronal and glial cell biology.

PMID- 20678923
TI  - Emerging themes of ER organization in the development and maintenance of axons.
AB  - The endoplasmic reticulum (ER) is a continuous membrane system comprising the
      nuclear envelope, polyribosome-studded peripheral sheets, and a polygonal network
      of smooth tubules extending throughout the cell. Though protein biosynthesis,
      transport, and quality control in the ER have been extensively studied,
      mechanisms underlying the heterogeneous architecture of the ER have been
      clarified more recently. These insights have increased interest in ER morphology
      changes associated with the development of neuronal axons and dendrites as well
      as their integration with presynaptic and postsynaptic signaling pathways. A
      number of proteins involved in shaping and distributing the ER network are
      mutated in neurological disorders, particularly the hereditary spastic
      paraplegias, emphasizing the importance of proper ER morphology for the
      establishment and maintenance of highly polarized neurons.

PMID- 20678924
TI  - Microwave-assisted pretreatment of recalcitrant softwood in aqueous glycerol.
AB  - Microwave-assisted pretreatment of recalcitrant softwood in aqueous glycerol
      containing a series of organic and inorganic acids with different pK(a) values
      was examined. The pulp obtained by organosolvolysis with 0.1% hydrochloric acid
      (pK(a) -6) at 180 degrees C for 6 min gave the highest sugar yield, 53.1%, based
      on the weight of original biomass. The pretreatment efficiency correlated
      linearly with the pK(a) of the acids, with the exception of malonic and
      phosphoric acids. Organosolvolysis with 1.0% phosphoric acid (pK(a) 2.15) gave a
      saccharification yield (50.6%) higher than that expected from its pK(a), while
      the catalytic effect of malonic acid (pK(a) 2.83) was negligible. Extensive
      exposure of crystalline and non-crystalline cellulose by the glycerolysis with
      strong inorganic acids was demonstrated by using fluorescent-labeled recombinant
      carbohydrate-binding modules (CBMs). Because of the low concentration of the acid
      catalysts and availability of glycerol as a by-product from biodiesel and fatty
      acid production, organosolvolysis in glycerol is an appealing process for
      pretreatment of recalcitrant softwood.

PMID- 20678925
TI  - Experimental study on a coupled process of production and anaerobic digestion of
      Chlorella vulgaris.
AB  - The main goal of this present study is to investigate the feasibility of coupling
      algae production (Chlorella vulgaris) to an anaerobic digestion unit. An
      intermediate settling device was integrated in order to adapt the feed-flow
      concentration and the flow rate. Digestion of C. vulgaris was studied under 16
      and 28 days hydraulic retention times (HRT), with a corresponding organic loading
      rate of 1g(COD)L(-1). Increasing the HRT achieved 51% COD removal with a methane
      production measured at 240 mL g(VSS)(-1). Performing different HRTs and dynamic
      monitoring during degradation highlighted differential hydrolysis of microalgae
      compartments. However, 50% of the biomass did not undergo anaerobic digestion,
      even under long retention times. This points out the interest for further studies
      on pre-treatment performances and more generally speaking on the need for
      intensifying microalgae biomass digestion.

PMID- 20678926
TI  - An integrated approach to the degradation of phytates in the corn wet milling
      process.
AB  - An integrated process was developed to hydrolyze the phytates in light steep
      water (LSW) and to simultaneously isolate inorganic phosphate (Pi) and myo
      inositol products. The proposed integrated process will be helpful in resolving
      the environmental and nutritional concerns in the use of corn gluten feed (CGF)
      in the animal diets. This process comprised of partial and total hydrolysis of
      LSW and intermediate anion exchange separation technique. The phytates in LSW
      were initially degraded to negatively charged myo-inositol phosphates (InsP(2)
      InsP(5)). The optimized experimental parameters for the partial hydrolysis of LSW
      were determined to be 2 h hydrolysis with 1FTU Aspergillus niger/g substrate at
      35 degrees C. The negatively charged species of the partially hydrolyzed
      substrate were separated on a strong base anion exchange resin. The negatively
      charged species, retained by the resin, were eluded with 1M NaCl solution and
      were subjected to complete hydrolysis with the Escherichia coli, A. niger derived
      phytases and their respective combinations. The maximum amount of myo-inositol
      released from the anion exchange column was 3.73+/-0.03 mg/NaCl elution which was
      detected after 48 h reactions catalyzed by 100 FTU E. coli, 150 FTU E. coli, and
      150 FTU the combination of A. niger and E. coli. The time course of Pi released
      showed a similar trend to that of myo-inositol and the released Pi reached a
      maximum amount of 3.30+/-0.05 mg/g NaCl elution after 48 h incubation at the
      enzyme loadings for which the maximum concentration of myo-inositol were reached.

PMID- 20678927
TI  - Optimizing cellulase usage for improved mixing and rheological properties of acid
      pretreated sugarcane bagasse.
AB  - Consolidation of bioprocessing steps with lignocellulose is limited by
      hydrolysate toxicity, the fibrous nature of suspensions, and low activity of
      cellulase enzymes. Combinations of enzyme dose and treatment conditions improved
      the flow properties and pumping of acid-pretreated sugarcane bagasse slurries
      (10% dry weight). Low levels of cellulase enzyme (0.1 and 0.5 FPU/g dry weight
      acid-pretreated bagasse) were found to reduce viscosities by 77-95% after 6 h,
      solubilizing 3.5% of the bagasse dry weight. Flow of slurries through small
      funnels was a useful predictor of success with centrifugal and diaphragm pumps.
      Equations were derived that describe viscosity and solubilized carbohydrates as a
      function of time and cellulase dosage. Blending of acid-pretreated bagasse (10%
      dry weight) with suspensions of acid-pretreated bagasse (10% dry weight) that had
      been previously digested with cellulase enzymes (low viscosity) did not increase
      viscosity in a linear fashion. Viscosity of these mixtures remained relatively
      constant until a threshold level of new fiber was reached, followed by a rapid
      increase with further additions. Up to 35% fresh acid-pretreated bagasse could be
      blended with enzyme-digested fiber (5.0 FPU/g dry weight acid-pretreated fiber; 6
      h) with only a modest increase in viscosity. The smooth surfaces of enzyme
      treated fiber are proposed to hinder the frequency and extent of interactions
      between fibrils of fresh fiber particles (acid-pretreated) until a threshold
      concentration is achieved, after which fiber interactions and viscosity increase
      dramatically. These results were used to model the viscosity in an ideal
      continuous stirred tank reactor (liquefaction) as a function of residence time
      and enzyme dosage.

PMID- 20678928
TI  - Treatment of azo dye Acid Orange 7 containing wastewater using up-flow
      constructed wetland with and without supplementary aeration.
AB  - The aim of this study is to examine and compare the treatment performance of Acid
      Orange 7 (AO7) containing wastewater by up-flow constructed wetland (UFCW) at
      different AO7 concentrations, hydraulic retention times (HRT) and alternative of
      supplementary aeration. The aerated wetland reactor outperformed the non-aerated
      one in the removal of organic matters, NH(4)-N and aromatic amines. The T-P
      removal efficiency for both wetland reactors was not much different throughout
      the study and the supplementary aeration showed no significant effect on T-P
      removal. As influent AO7 concentration increased from 50 to 100 mg/L, the
      performance in biodegradation of organic matters and nitrification in the non
      aerated wetland reactor, and denitrification and decolorization in the aerated
      wetland reactor were affected. As HRT increased from 3 to 6 d, the removal of
      NH(4)-N and NO(3)-N in the aerated wetland reactor was not significantly
      different, but the NH(4)-N removal efficiency improved tremendously in the non
      aerated wetland reactor.

PMID- 20678929
TI  - Sludge granulation and performance of a low superficial gas velocity sequencing
      batch reactor (SBR) in the treatment of prepared sanitary wastewater.
AB  - A sequencing batch reactor (SBR) employing a low superficial gas velocity was
      used to produce aerobic granular sludge for wastewater treatment. At a gas
      velocity of 0.0056 m s(-1) sludge containing a mixture of light yellow and black
      granules with similar functional groups was quickly formed. The black granules
      contained crystals of CaCO(3), FeS, and Fe(2)O(3) as well as filamentous bacteria
      that strengthened the particles and reduced the mass transfer resistance. No
      inorganic crystals were detected in the yellow sludge granules, and their
      structure was maintained through cohesion mediated by extracellular polymeric
      substances (EPS). The light yellow granules were denser and offered better
      settling performance than the black granules, enhancing the settling properties
      of the mixed sludge. During a 12-h cycle, the maximum reductions in chemical
      oxygen demand (COD), NH(3)-N, and total nitrogen (TN) occurred at 240, 480, and
      360 min with removal efficiencies of 90%, 90%, and 54%. When the cycle time was
      limited to 480 min, self-dissolution of the granules was avoided while sill
      maintaining removal efficiencies for COD, NH(3)-N, and TN of 88%, 90%, and 53%.

PMID- 20678930
TI  - Synthetic multi-component enzyme mixtures for deconstruction of lignocellulosic
      biomass.
AB  - A high throughput enzyme assay platform, called GENPLAT, was used to guide the
      development of an optimized mixture of individual purified enzymes from ten
      "accessory" and six "core" enzymes. Enzyme mixtures were optimized for release of
      Glu, Xyl, or a combination of the two from corn stover pretreated by ammonia
      fiber expansion (AFEX). Assay conditions were a fixed enzyme loading of 15 mg/g
      glucan, 48 h digestion, and 50 degrees C. Five of the ten tested accessory
      proteins enhanced Glu or Xyl yield compared to the core set alone, and five did
      not. An 11-component mixture containing the core set and five accessory enzymes
      optimized for Glu released 52.1% of the available Glu, compared to 38.5% with the
      core set alone. A mixture optimized for Xyl released 39.9% of the Xyl, compared
      to 26.4% with the core set alone. We predict that there is still considerable
      opportunity for further improvement of synthetic mixtures. Furthermore, the
      strategy described here is applicable to the development of more efficient enzyme
      cocktails for any pretreatment/biomass combination and for detecting enzymes that
      make a heretofore unrecognized contribution to lignocellulose deconstruction.

PMID- 20678931
TI  - Substituted 2H-isoquinolin-1-ones as potent Rho-kinase inhibitors: part 2,
      optimization for blood pressure reduction in spontaneously hypertensive rats.
AB  - Phenylglycine substituted isoquinolones 1 and 2 have previously been described as
      potent dual ROCK1/ROCK2 inhibitors. Here we describe the further SAR of this
      series to improve metabolic stability and rat oral exposure. Piperidine analog 20
      which demonstrates sustained blood pressure normalization in an SHR blood
      pressure reduction model was identified through this effort.

PMID- 20678932
TI  - Synthesis and biological evaluation of new jasplakinolide (jaspamide) analogs.
AB  - Synthesis and biological evaluation of jasplakinolide analogs are described. The
      synthesis of analogs utilized a diastereoselective syn-aldol reaction and an
      orthoester Claisen rearrangement as key steps. All synthetic analogs were
      evaluated for their ability to disrupt the actin cytoskeleton. Compounds 2, 3,
      and 4 essentially displayed similar activity to jasplakinolide.

PMID- 20678933
TI  - Natural products-based insecticidal agents 7. Semisynthesis and insecticidal
      activity of novel 4alpha-alkyloxy-2-chloropodophyllotoxin derivatives against
      Mythimna separata Walker in vivo.
AB  - In continuation of our program aimed at the discovery and development of natural
      products-based insecticidal agents, 16 novel 4alpha-alkyloxy-2
      chloropodophyllotoxin derivatives were semisynthesized from podophyllotoxin, and
      preliminarily evaluated for their insecticidal activity against the pre-third
      instar larvae of Mythimna separata Walker in vivo. Among all the tested
      derivatives, especially compounds 4b, 4e, 4g, and 4p exhibited more promising and
      pronounced insecticidal activity than toosendanin, a commercial insecticide
      derived from Melia azedarach. Generally, it was obviously demonstrated that the
      length of straight-chain or branched-chain alkyloxy, and heteroatom-containing
      cycloalkyloxy at the C-4 position of 2-chloropodophyllotoxin were very important
      for the insecticidal activity.

PMID- 20678934
TI  - Introduction of guanidinium-modified deoxyuridine into the substrate binding
      regions of DNAzyme 10-23 to enhance target affinity: implications for DNAzyme
      design.
AB  - Deoxyribozymes (DNAzymes) are important catalysts for potential therapeutic RNA
      destruction and no DNAzyme has received as much notoriety in terms of therapeutic
      use as the Mg(2+)-dependent RNA-cleaving DNAzyme 10-23 (Dz10-23). As such, we
      have investigated the synthetic modification of Dz10-23 with a guanidinium group,
      a functionality that reduces the anionic nature and can potentially enhance the
      membrane permeability of oligonucleotides. To accomplish this, we synthesized a
      heretofore unknown phosphoramidite, 5-(N,N'-biscyanoethoxycarbonyl)
      guanidinoallyl-2'-deoxyuridine and then incorporated it into oligonucleotides via
      solid phase synthesis to study duplex stability and its effect on Dz10-23. This
      particular modification was chosen as it had been used in the selection of Mg(2+)
      free self-cleaving DNAzymes; as such this will enable the eventual comparison of
      modified DNAzymes that do or do not depend on Mg(2+) for catalysis. Consistent
      with antecedent studies that have incorporated guanidinium groups into DNA
      oligonucleotides, this guanidinium-modified deoxyuridine enhanced the thermal
      stability of resulting duplexes. Surprisingly however, Dz10-23, when synthesized
      with modified residues in the substrate binding regions, was found to be somewhat
      less active than its non-modified counterpart. This work suggests that this
      particular system exhibits uniform binding with respect to ground state and
      transition state and provides insight into the challenge of re-engineering a
      Mg(2+)-dependent DNAzyme with enhanced catalytic activity.

PMID- 20678935
TI  - Synthesis of novel tetrahydroisoquinoline bronchodilators.
AB  - The synthesis and bronchorelaxing effects of a series of novel
      tetrahydroisoquinoline amides are described. The compounds were evaluated for
      their ability to relax LTD4 contracted isolated human small airways ex-vivo.
      Several compounds demonstrated highly efficacious bronchorelaxing properties.
      Cinnamide 71 was selected for further studies and constitutes a promising
      candidate as a novel bronchorelaxing agent for the treatment of pulmonary
      disorders.

PMID- 20678936
TI  - Validity and reliability of upper extremity three-dimensional kinematics during a
      typing task.
AB  - Computer use continues to be considered a risk factor for work-related
      musculoskeletal disorders despite a greater awareness of the risk associated with
      excessive use, the implementation of safety features and the introduction of
      extensive interventional programs. Better understanding of risk factors in
      movement patterns is needed. This study identified the most suitable variable for
      work-related upper extremity motion analysis as being peak-to-peak range of
      motion. Assessment was by three-dimensional motion analysis for upper extremity
      ergonomics. The study was designed to validate and examine the reliability of
      these parameters in the setting of keyboarding. Sixty-two right-hand dominant
      participants (non-skilled typists) were recruited. Motion analysis was performed
      using the Cartesian Optoelectronic Dynamic Anthropometric CX-1 (CODA) system with
      markers which were attached to the right hand, elbow, wrist and fingers. Range of
      motion and angular velocity were recorded while the subjects repeatedly typed a
      predetermined sentence five times. The re-test examination was repeated after an
      interval of one week. The findings clearly demonstrated discriminative validity
      in wrist range of motion (p<.01), test-re-test, reliability (.83>ICC>.70) and
      inter-rater reliability (.95>ICC>.70) for most variables. The CODA system has
      considerable potential for understanding movement patterns in the upper
      extremities. These findings can provide the basis for future studies on the
      efficacy of ergonomic intervention programs.

PMID- 20678937
TI  - Gait symmetry improves in childhood--a 4-year follow-up of foot loading data.
AB  - Children under 10 years of age are less efficient than adults regarding their
      dynamic balance control. The development of the somatosensory system is necessary
      for the control of posture and balance. The foot, as the final link between body
      and ground, transfers internal forces during gait. The coordination of force
      transfer needs to be balanced between both feet thus leading to a potential
      asymmetry of foot loading. The magnitude of asymmetry in infants' gait has been
      previously studied. However, the individual development and improvement of gait
      symmetry should also be considered. Therefore, the aim of this study was to
      retrospectively evaluate the longitudinal development of foot loading symmetries
      from the onset of independent walking. Sixty-two healthy infants were followed
      over the course of 4 years by means of plantar pressure distribution measurements
      (mean age of 15 months at study start and 63 months at the end). The subjects
      attended a total of nine measurements scheduled every 6 months. Foot loading data
      was recorded during walking with the emed((r)) pressure platform to evaluate
      contact area, peak pressure, force-time integral, relative maximum force and
      contact time. An absolute symmetry index was calculated for all parameters.
      Furthermore, the infants' data were compared to the data of 26 healthy adults.
      The adults were measured once and the data acquisition followed exactly the same
      procedures as the infants' data. In conclusion, foot loading is asymmetric with
      the onset of independent walking and shows improved symmetry with increasing age
      dependent on the foot loading parameters.

PMID- 20678938
TI  - Strength asymmetry and osteoarthritis risk factors in unilateral trans-tibial,
      amputee gait.
AB  - Persons with a unilateral, trans-tibial amputation have an increased risk of
      developing osteoarthritis (OA) in the knee of their intact limb. Between-side
      strength discrepancies observed in individuals with an amputation may indicate
      overuse of the intact limb and increased osteoarthritis risk; however, the
      relationship between lower extremity strength and gait mechanics has not been
      addressed in previous literature. It was hypothesized that amputee subjects'
      strength and gait would be more asymmetrical than controls, and that strength
      asymmetry would positively correlate with gait variable asymmetry and intact side
      gait variables associated with osteoarthritis risk. Eight persons with
      unilateral, trans-tibial amputation and eight able-bodied control subjects
      participated. Three gait variables related to osteoarthritis risk (knee external
      adduction moment, knee adduction moment load rate, and vertical ground reaction
      force load rate) were measured bilaterally, along with three strength measures
      (hip abductors, knee extensors, and knee flexors). Four of the six variables were
      more asymmetrical in the amputee group than the control group (p<0.05 and/or
      effect size greater than 0.70). Knee extension strength asymmetry was
      significantly related to knee adduction moment load rate asymmetry (rho=0.714),
      and knee flexion strength asymmetry was moderately related to the vertical ground
      reaction force on the intact limb (rho=0.643). Results suggest that strength
      asymmetry in unilateral trans-tibial amputees has a moderate relationship with
      osteoarthritis risk, and may be a useful way to assess gait ability and the need
      for rehabilitation in this population.

PMID- 20678939
TI  - Kinematic adaptations to ischemic pain in claudicants during continuous walking.
AB  - Intermittent claudication has been associated with impaired gait and balance. The
      study aim was to compare gait adaptations over time between claudicants
      classified with good versus poor balance. Kinematic data were collected from 24
      claudicants during continuous walking. Balance was assessed using; Timed Up and
      Go test (TUG), and Sensory Organisation (SOT) and Motor Control (MCT) Tests using
      NeuroCom Equitest(r). 'Good balance' (GB) was operationally defined as those
      claudicants achieving normal scores on at least 2 of 3 tests whereas 'poor
      balance' (PB) claudicants achieved normal scores on 0 or 1 test. Temporal-spatial
      and sagittal plane joint kinematics were analysed at three time intervals; 'no
      pain' (prior to onset), 'initial pain' and 'maximal pain' (unable to continue
      walking). A two-way mixed design ANOVA was performed. Claudicants demonstrated a
      significant decrease in walking speed, step frequency and increased time in
      double support (p<0.05). Inter-group analysis showed no differences between GB
      and PB on any temporal-spatial or kinematic parameters (p>0.05). There was no
      significant time and group interaction for any temporal-spatial or kinematic
      variable except hip flexion. GB claudicants demonstrated increased hip flexion as
      pain progressed but this adaptive strategy was not seen in PB claudicants.
      Claudicants make adaptations to walking by slowing (down) when in pain.
      Differences between GB and PB were not seen in temporal-spatial or ankle, knee
      and pelvic kinematic gait parameters. However adaptation to pain in GB
      claudicants involved a hip strategy, not seen in PB claudicants.

PMID- 20678940
TI  - Vertical atlantoaxial dislocation as a cause of failure of midline fixation.
AB  - We report an 11-year-old girl who had previously undergone an operation for
      basilar invagination involving a foramen magnum decompression and midline wire
      fixation. After improving initially, her neurological condition worsened again.
      Repeated investigations showed a firm midline craniovertebral fixation and bone
      fusion. However, she was found to have a vertical mobile and reducible
      atlantoaxial dislocation. Treatment of the vertical dislocation by lateral mass
      fixation resulted in lasting relief from her symptoms. Vertical instability at
      the atlantoaxial joints needs to be identified and appropriately treated as it
      may be a cause of failure of midline fixation.

PMID- 20678941
TI  - Confocal Raman and electronic microscopy studies on the topotactic conversion of
      calcium carbonate from Pomacea lineate shells into hydroxyapatite bioceramic
      materials in phosphate media.
AB  - Conversion of Pomacea lineate shells into hydroxyapatite (HA) bioceramic
      materials was investigated by their in vitro treatment with phosphate solutions,
      at room temperature. Confocal Raman microscopy revealed that the conversion
      proceeds at distinct rates through the nacreous or periostracum sides of the
      shell. The conversion can be accelerated using powdered samples, yielding
      biocompatible materials of great interest in biomedicine.

PMID- 20678943
TI  - The usability of tree barks as long term biomonitors of atmospheric radionuclide
      deposition.
AB  - In view of the lower radionuclide activities of moss and lichen, tree barks can
      be used as biomonitors of radioactive contamination, regardless of the
      contribution of soil uptake. The present study was conducted to determine the
      activity concentrations of (137)Cs, (40)K, (232)Th and (238)U in the barks of
      pine (Pinus nigra) and oak (Quercus petraea) trees collected from the Thrace
      region in Turkey. By considering the previous studies carried out in the same
      region, it is noticed that among lichen, moss, oak bark and pine bark, oak bark
      is the best accumulator of (137)Cs and natural radionuclides.

PMID- 20678942
TI  - Electron cryomicroscopy of membrane proteins: specimen preparation for two
      dimensional crystals and single particles.
AB  - Membrane protein structure and function can be studied by two powerful and highly
      complementary electron cryomicroscopy (cryo-EM) methods: electron crystallography
      of two-dimensional (2D) crystals and single particle analysis of detergent
      solubilized protein complexes. To obtain the highest-possible resolution data
      from membrane proteins, whether prepared as 2D crystals or single particles, cryo
      EM samples must be vitrified with great care. Grid preparation for cryo-EM of 2D
      crystals is possible by back-injection, the carbon sandwich technique, drying in
      sugars before cooling in the electron microscope, or plunge-freezing. Specimen
      grids for single particle cryo-EM studies of membrane proteins are usually
      produced by plunge-freezing protein solutions, supported either by perforated or
      a continuous carbon film substrate. This review outlines the different techniques
      available and the suitability of each method for particular samples and studies.
      Experimental considerations in sample preparation and preservation include the
      protein itself and the presence of lipid or detergent. The appearance of cryo-EM
      samples in different conditions is also discussed.

PMID- 20678944
TI  - Discharged photoprotein obelin: fluorescence peculiarities.
AB  - Photoprotein obelin, the enzyme-substrate complex of polypeptide with 2
      hydroperoxycoelenterazine, is responsible for bioluminescence of marine hydroid
      Obelia longissima. Addition of Ca(2+) to the photoprotein triggers the
      bioluminescent reaction with light emission. The product of the bioluminescent
      reaction--enzyme-bound coelenteramide--is a fluorescent protein called
      'discharged' obelin. It is stable and highly fluorescent. The paper considers
      dependence of its light-induced fluorescence on Ca(2+) concentration. Increase of
      Ca(2+) concentration enhanced the fluorescence intensity of discharged obelin;
      the dependence was found as linear in double logarithmic coordinates at Ca(2+)
      concentration range 10(-7)-10(-6) M, both in excitation and emission spectra. The
      spectra were divided into components; contributions of the components to
      experimental excitation and emission spectra depended on Ca(2+) concentration.
      The data suggest enzymatic conformational transition in discharged obelin at
      approximately 5 x 10(-7) M of Ca(2+) concentration. Spectra variations were
      attributed to acidity changes of discharged obelin chromophore (coelenteramide)
      in its fluorescent state S(1)*.

PMID- 20678945
TI  - Unusual ion UO(4)(-) formed upon collision induced dissociation of
      [UO(2)(NO(3))(3)](-), [UO(2)(ClO(4))(3)](-), [UO(2)(CH(3)COO)(3)](-) ions.
AB  - The following ions [UO(2)(NO(3))(3)](-), [UO(2)(ClO(4))(3)](-),
      [UO(2)(CH(3)COO)(3)](-) were generated from respective salts (UO(2)(NO(3))(2),
      UO(2)(ClO(4))(3), UO(2)(CH(3)COO)(2)) by laser desorption/ionization (LDI).
      Collision induced dissociation of the ions has led, among others, to the
      formation of UO(4)(-) ion (m/z 302). The undertaken quantum mechanical
      calculations showed this ion is most likely to possess square planar geometry as
      suggested by MP2 results or strongly deformed geometry in between tetrahedral and
      square planar as indicated by DFT results. Interestingly, geometrical parameters
      and analysis of electron density suggest it is an U(VI) compound, in which oxygen
      atoms bear unpaired electron and negative charge.

PMID- 20678946
TI  - Long term clinical and electrophysiological assessment of Croatian children with
      corticospinal tract involvement in Guillain-Barre syndrome (GBS).
AB  - Guillain-Barre syndrome (GBS) is characterized by areflexia. Hyperreflexia is
      reported in acute motor axonal neuropathy (AMAN). We present 16 children with GBS
      at the age of 14 months to 13 years. All children studied fulfilled accepted
      diagnostic criteria for GBS. Hyperreflexia or positive Babinski sign were
      obtained in all children studied during follow up. Brain and spinal cord MR scans
      did not reveal any significant structural and morphological abnormalities of
      central nervous system. The children were examined clinically and
      electromyoneurographically 2-5 times successively during 1-8.5 years of follow
      up. According to established electrodiagnostic criteria demyelinating form of GBS
      was most common (68%) compared to axonal (18,7%) or mixed form (12,5%). No
      children had antecendent Campylobacter jejuni infection. Antiganglioside
      antibodies were detected in 18,7% of patients associated with demyelinating or
      mixed (axonal/demyelinating) form. Time to nadir and recovery period of walking
      ability is prolonged more often in demyelinating GBS. Clinical improvement occur
      earlier compared to improvement of abnormal electrophysiological
      parameters.Outcome was excellent in 11 in the period 1 month-8.5 years.
      Hyperreflexia usually appeared in recovery period suggesting involvement of upper
      motor neurons or spinal interneurons occurring in Croatian children with both
      demyelinating and axonal form of GBS usually associated with milder course of
      disease.

PMID- 20678947
TI  - Distance measurement between a spin-1/2 and a half-integer quadrupolar nuclei by
      solid-state NMR using exact analytical expressions.
AB  - We show that the S-RESPDOR NMR method can be used to measure distances between
      spin-1/2 and half-integer quadrupolar nuclei, and that a general analytical
      formula describes its dephasing curve for all spin values. We demonstrate the
      method on the C4-O4 spin pair of L-tyrosine.HCl, with 13C natural abundance and
      30% 17O enrichment, using a moderate magnetic field (9.4 T), a moderate 17O rf
      field (40 kHz) and a fast spinning speed (22 kHz). It is shown that S-RESPDOR is
      much more robust and accurate than previous methods.

PMID- 20678948
TI  - Suboptimal outcomes in patients with PKU treated early with diet alone:
      revisiting the evidence.
AB  - BACKGROUND: The National Institute of Health (NIH) published a Consensus
      Statement on the screening and management of Phenylketonuria (PKU) in 2000. The
      panel involved in the development of this consensus statement acknowledged the
      lack of data regarding the potential for more subtle suboptimal outcomes and the
      need for further research into treatment options. In subsequent years, the
      approval of new treatment options for PKU and outcome data for patients treated
      from the newborn period by dietary therapy alone have become available. We
      hypothesized that a review of the PKU literature since 2000 would provide further
      evidence related to neurocognitive, psychosocial, and physical outcomes that
      could serve as a basis for reassessment of the 2000 NIH Consensus Statement.
      METHODS: A systematic review of literature residing in PubMed, Scopus and
      PsychInfo was performed in order to assess the outcome data over the last decade
      in diet-alone early-treated PKU patients to assess the need for new
      recommendations and validity of older recommendations in light of new evidence.
      RESULTS: The majority of publications (140/150) that contained primary outcome
      data presented at least one suboptimal outcome compared to control groups or
      standardized norms/reference values in at least one of the following areas:
      neurocognitive/psychosocial (N=60; 58 reporting suboptimal outcomes); quality of
      life (N=6; 4 reporting suboptimal outcomes); brain pathology (N=32; 30 reporting
      suboptimal outcomes); growth/nutrition (N=34; 29 reporting suboptimal outcomes);
      bone pathology (N=9; 9 reporting suboptimal outcomes); and/or maternal PKU (N=19;
      19 reporting suboptimal outcomes). CONCLUSIONS: Despite the remarkable success of
      public health programs that have instituted newborn screening and early
      introduction of dietary therapy for PKU, there is a growing body of evidence that
      suggests that neurocognitive, psychosocial, quality of life, growth, nutrition,
      bone pathology and maternal PKU outcomes are suboptimal. The time may be right
      for revisiting the 2000 NIH Consensus Statement in order to address a number of
      important issues related to PKU management, including treatment advancements for
      metabolic control in PKU, blood Phe variability, neurocognitive and psychological
      assessments, routine screening measures for nutritional biomarkers, and bone
      pathology.

PMID- 20678949
TI  - Management by objectives and its impact on specialist prescription quality at
      discharge and in external consultations.
AB  - OBJECTIVE: To verify that implementing a policy of management by objectives,
      based on collaboration between hospital pharmacy, primary care and specialised
      medical managers, improves prescription quality indicators in specialised care
      and reduces unwanted "induced" prescriptions (i.e. those issued by specialists,
      hospital doctors or the patients themselves) in primary care. METHOD: A four year
      quasi-experimental controlled intervention study on prescription at discharge and
      in outpatient hospital consultations was conducted. In hospital A, a quality
      cycle was applied: assessment, identifying improvement opportunities,
      implementing corrective actions and re-assessment. However, it was not applied in
      control hospital B. The indicators chosen were the percentage of generic
      medicines prescribed, the percentage of prescriptions for new therapies with no
      added value and the percentage of prescriptions for ACE inhibitors recommended.
      RESULTS: In hospital A, an increase in indicators 1 and 3 has been observed, both
      being statistically significant, between the last year of intervention and the
      year previous to intervention. Hospital A managed to reduce indicator 2 to 4.5%,
      while this indicator increased in hospital B to 8.8%. Furthermore, a
      statistically significant difference in indicators between the two hospitals has
      been registered. CONCLUSION: Pay-for-Performance programs in prescription
      practices of hospital physicians are effective actions to improve quality
      indicators of medication use.

PMID- 20678951
TI  - Tattooing and the risk of transmission of hepatitis C: a systematic review and
      meta-analysis.
AB  - OBJECTIVES: In this systematic literature review we sought to determine whether
      tattooing is a risk factor for the transmission of hepatitis C. METHODS: A
      comprehensive search was performed to identify all case-control, cohort or cross
      sectional studies published prior to November 2008 that evaluated risks related
      to tattooing or risk factors of transmission of hepatitis C infection. RESULTS: A
      total of 124 studies were included in this systematic review, of which 83 were
      included in the meta-analysis. The pooled odds ratio (OR) and 95% confidence
      interval (CI) of the association of tattooing and hepatitis C from all studies
      was 2.74 (2.38-3.15). In a subgroup analysis we found the strongest association
      between tattooing and risk of hepatitis C for samples derived from non-injection
      drug users (OR 5.74, 95% CI 1.98-16.66). CONCLUSIONS: Findings from the current
      meta-analysis indicate that tattooing is associated with a higher risk of
      hepatitis C infection. Because tattooing is more common among the youth and young
      adults and hepatitis C is very common in the imprisoned population, prevention
      programs must focus on youngsters and prisoners to lower the spread of hepatitis
      infection.

PMID- 20678950
TI  - [Evolution of antiretroviral treatment adherence from 2000 to 2008].
AB  - OBJECTIVES: To evaluate antiretroviral treatment adherence in the HIV patient
      cohort of our hospital and observe their evolution over a 9-year period; also to
      determine the individual pattern of adherence over time. METHODS: Descriptive
      study of the evolution of average annual adherence and the annual percentage of
      adherent patients greater than 95% from 2000 to 2008. We analysed the individual
      pattern of adherence over time and patients were classified into consistently
      adherent, consistently non-adherent, and fluctuating. RESULTS: In the analysis of
      577 patients, baseline adherence was significantly greater in naive patients with
      respect to those who were pre-treated. Average annual adherence increased
      slightly and stayed at values around 95%. As with the percentage of patients with
      adherence greater than 95%, which increased from 64% in 2000 to 79% in 2008. In
      terms of the individual pattern of adherence over time, of the 468 patients
      analysed, the majority (59%) were consistently adherent, 4% non-adherent, and the
      rest (37%) fluctuated in their adherence. CONCLUSIONS: In our cohort the overall
      adherence values maintained themselves over time and even show a positive trend,
      likely the result of systematic monitoring of adherence and implementation
      strategies to maintain adherence.

PMID- 20678952
TI  - Detection of the four major human herpesviruses simultaneously in whole blood and
      cerebrospinal fluid samples by the fluorescence polarization assay.
AB  - OBJECTIVES: Herpes simplex virus type 1/2 (HSV-1/-2), cytomegalovirus (CMV), and
      Epstein-Barr virus (EBV) correlate strongly with infections of the central
      nervous system. The objective of this study was to develop a method for the
      simultaneous detection of HSV-1/-2, CMV, and EBV DNA by the fluorescence
      polarization assay based on asymmetric polymerase chain reaction (PCR) and
      hybridization. METHODS: DNA of HSV-1/-2, CMV, and EBV was amplified in an
      asymmetric PCR by a universal primer system. The amplicons were then detected by
      the fluorescence polarization assay. In this method, the probes for HSV-1/-2,
      CMV, and EBV hybridized with their respective target amplicons, and the
      hybridization resulted in an increase in the fluorescence polarization values.
      Infections of HSV-1/-2, CMV, and EBV were determined by the increased
      fluorescence polarization values. The DNA extracted from whole blood and
      cerebrospinal fluid samples was subjected to fluorescence polarization and a
      previously published multiplex PCR assay in parallel. RESULTS: Compared to the
      multiplex PCR assay, no significant difference in the numbers of samples positive
      for the human herpesviruses was identified by the fluorescence polarization
      assay. CONCLUSIONS: The fluorescence polarization assay presented in this study
      is a reliable, convenient, and cost-effective diagnostic tool that allows the
      detection of the four major human herpesviruses.

PMID- 20678953
TI  - Enhancement and control of acoustic cavitation yield by low-level dual frequency
      sonication: a subharmonic analysis.
AB  - Evaluation of inertial cavitation is a significant problem where this mechanism
      of action is responsible for therapeutic applications such as drug delivery. It
      has shown that using multiple frequencies one is able to enhance and control
      induced cavitation. In this study, we used different sonication frequencies as 28
      kHz, 130 kHz, 1 MHz, 3 MHz and their dual combinations to enhance acoustic
      cavitation. At each frequency, two different intensities were used and the
      subharmonic amplitude of each frequency in combinations was measured. It was
      observed that in combinations which include 28 kHz, the cavitation activity is
      enhanced. The 28 kHz subharmonic amplitude was used to compare these protocols in
      their ability to enhance cavitation. Besides, the area of cavitation damage was
      determined using an aluminum foil. Our results showed that the inertial
      cavitation activity increased at higher intensities and there is a significant
      correlation between the subharmonic amplitude and sonication intensity at each
      frequency (R>0.90). In addition, simultaneous combined dual-frequency orthogonal
      sonication at 28 kHz with other frequencies used can significantly increase the
      inertial cavitation activity as compared to the algebraic sum of the individual
      ultrasound irradiations in 28 kHz subharmonic frequency. The 28 kHz subharmonic
      amplitude for 28 kHz (0.04 W/cm(2)) and 3 MHz (2 and 1 W/cm(2)) combined dual
      frequency were about 4.6 and 1.5 times higher than that obtained from the
      algebraic sum of 28 kHz and 3 MHz irradiation, respectively. Also the 28 kHz
      subharmonic amplitude for combination of 28 kHz (0.04 W/cm(2)) and 1 MHz (2 and 1
      W/cm(2)) were about 2.4 and 1.6 times higher than that obtained with their
      algebraic sum. Among different combinations, the continuous mode for two
      ultrasound sources of 28 kHz (0.04 W/cm(2)) and 3 MHz (2 W/cm(2)) is more
      effective than other combinations (p-value<0.05). The results of effective
      irradiation area showed no damaged aluminum foil in MHz sonication alone.
      However, there is significant difference between the effective irradiation area
      of combined dual frequency 28 kHz and 3 MHz with other irradiation modes (p
      value<0.05) and it is limited locally.

PMID- 20678954
TI  - Dynamic measurement of lumbar curvature using fibre-optic sensors.
AB  - Dynamic continuous measurement of the curvature of the lumbar spine is
      technically difficult but could provide important information about the functions
      of the spine. A new measurement system using a ribbon of specifically modified
      fibre-optic sensors was attached to the back and used to dynamically measure
      lumbar surface curvature during flexion and lifting. Reliability of the collected
      data and comparison to a video-based system were investigated in thirteen
      participants for curvature of both the lower and whole lumbar spine. The
      coefficients of multiple correlation of repeated measurements of curvature-time
      curves were found to be high, 0.97-0.98, and all measurements were as reliable as
      data obtained by the video method (0.93-0.97). Root mean square error values were
      below 2.5 degrees  for the fibre-optic system. Reattachment reliability was found
      to be excellent (0.91-0.97) as were comparisons to a video-based method (0.84
      0.95). It is concluded that the fibre-optic motion analysis system is capable of
      reliably measuring sagittal lumbar curvature across time and offers the ability
      to provide information regarding sequencing and relative motion between specific
      regions of the lumbar spine.

PMID- 20678955
TI  - Predictive factors affecting early deterioration of axial symptoms after
      subthalamic nucleus stimulation in Parkinson's disease.
AB  - Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment
      option for medically refractory Parkinson's disease (PD). However, some patients
      show deterioration of axial symptoms within a short time after surgery. We
      studied 43 patients who underwent bilateral STN-DBS and investigated predictive
      factors affecting early deterioration of axial symptoms. Among 43 patients, 16
      patients showed obvious deterioration of axial symptoms within three years of
      surgery. Multiple logistic regression analysis indicated that the significant
      independent variables related to early deterioration of axial symptoms were
      rapidly progressive short duration of the disease and advanced age at surgery.
      These results suggest that patients with rapidly progressing PD, who need early
      surgical intervention, tend to show early deterioration of axial symptoms after
      STN-DBS.

PMID- 20678956
TI  - Rehabilitative ultrasound imaging for assessment and treatment of musculoskeletal
      conditions.

PMID- 20678957
TI  - Synthesis, characterization and bioactive evaluation of copper(II) 5,10,15,20
      tetrakis[alpha,alpha,alpha,alpha-2-(2,6-bis(4-methylpiperazine-1-yl-methyl)-4
      iminomethyl phenol)phenyl] porphyrin: a picket-fence porphyrin.
AB  - We are interested in constructing deeper small cavities by adding more bulky
      substituents at the ortho-phenyl positions of tetrakis(o-aminophenyl)porphyrin.
      The synthesis of picket-fence porphyrin is initiated by the preparation of the
      tetrakis(o-nitrophenyl)porphyrin followed by the nitro to amino reduction and
      subsequent condensation with Schiff base ligand to form imine linkages of
      porphyrin complexes. The synthesis and characterization of a new series of picket
      fence porphyrins and their copper complexes are described. 5,10,15,20
      Tetrakis[alpha,alpha,alpha,alpha-2-(2,6-bis(4-methyl piperazine-1-yl-methyl)-4
      iminomethyl phenol)phenyl] porphyrin can be synthesized from 2,6-bis[4
      methylpiperazin-1-yl-methyl]-4-formylphenol (L) and 5,10,15,20
      tetra[alpha,alpha,alpha,alpha-o-nitropheny1]-porphyrin. 5,10,15,20
      Tetra[alpha,alpha,alpha,alpha-o-aminopheny1]-porphyrin was obtained by the
      reduction of 5,10,15,20-tetra[alpha,alpha,alpha,alpha-o-nitropheny1]-porphyrin.
      The spectral, electrochemical, antibacterial, antifungal and cytotoxicity
      properties of all the picket-fence porphyrin complexes were characterized and
      studied.

PMID- 20678958
TI  - Synthesis, characterization and properties of tetra((1-hydroxyimino
      methylnaphthalen-2-yloxy)methyl)ethene and its homo-dinuclear metal complexes: a
      combined experimental and theoretical investigation.
AB  - Tetra((1-hydroxyiminomethylnaphthalen-2-yloxy)methyl)ethene (THIMNYOME), H(4)L,
      was synthesized by the agents of 2-hydroxy-1-naphtaldehyde,
      tetra(bromomethyl)ethene and hydroxylamine hydrochloride in two steps.
      Characterization of THIMNYOME and its dinuclear complexes was made by elemental
      analyses, IR, (1)H- and (13)C NMR, UV-vis, electrospray ionisation mass spectra,
      molar conductivities and magnetic susceptibility measurements. In the light of
      these results, it was suggested that the ligand coordinate to each metal atom by
      the two ether oxygen, two nitrogen atoms of oxime imine (CN) and an axial oxygen
      of perchlorate to form pseudo square-pyramidal complexes with Ni(II), Cu(II) and
      Zn(II). Molar conductivity measurements reveal that all the complexes are non
      electrolytes. In addition, the full geometric optimization of the tetraoxime
      ligand (4) has been made by the B3LYP/6-31G(d) level in order to establish a
      stable conformation. Additionally, all the complex structures have been studied
      in the B3LYP/LANL2DZ level. NBO charge distribution and the characteristics of
      frontier molecular orbitals of these complexes have also been investigated in
      order to see the electrons movement between ligand and metal atom in the same
      level.

PMID- 20678959
TI  - Hepatitis E virus excretion can be prolonged in patients with hematological
      malignancies.
AB  - BACKGROUND: Hepatitis E virus (HEV) is transmitted via the fecal-oral route and
      locally acquired sporadic hepatitis E can occur in Western countries. Chronic
      hepatitis E virus infections have been recently described in solid organ
      transplant recipients. There is little data on the evolution of hepatitis E in
      patients immunocompromised for other reasons. OBJECTIVES: The aim of this study
      was to evaluate the clinical course of hepatitis E in patients immunocompromised
      because of hematological malignancies. STUDY DESIGN: Starting on November 2003,
      all patients in the Toulouse University Hospital Hematology Department with
      unexplained elevated transaminases were tested for hepatitis E using viral RNA
      detection in serum or stools and serology. RESULTS: Acute hepatitis E was
      diagnosed in six middle-aged hematology patients. All cases were autochthonous.
      HEV strains were genotype 3. All patients had a significant increase of
      transaminases (6-95 upper limit normal) and only two had HEV IgG. Five patients
      were asymptomatic and one had jaundice. Transmission of HEV occurred between two
      patients who had overlapping stays in the hematology ward. All five evaluable
      patients ultimately cleared their HEV but viremia was prolonged over 6 months in
      three patients and specific treatment had to be postponed in two patients.
      CONCLUSION: Screening for HEV should be carried out routinely in hematology
      patients with elevated transaminases, and patient-to-patient transmission is a
      concern. Further studies are required to determine whether management of
      malignancy, particularly stem-cell transplantation should be adapted to HEV
      status.

PMID- 20678960
TI  - Nurse led electronic toxicity scoring in head and neck radiotherapy.
AB  - PURPOSE OF THE STUDY: In order to improve 'adherence' to a course of treatment
      for head and neck radiotherapy, patients need to be managed frequently. In order
      to achieve this in a busy clinical environment streamlined electronic tools must
      be utilised. By providing nursing teams with the capacity to conduct electronic
      toxicity scoring on a bi-weekly basis, adherence can be improved and closer
      attention paid to head and neck radiotherapy toxicities. METHODS AND MATERIALS: A
      convenience sample of 20 patients undergoing head and neck radiotherapy was
      analysed. Each of these patients had electronic toxicity data recorded on a bi
      weekly basis for dysphagia, mucositis, skin reaction and weight loss. This
      information was then extracted from the ARIATM patient information system and
      analysed. Additionally the time taken for the nursing team to undertake each
      patient review was also extracted from ARIATM. RESULTS: The efficiencies offered
      by an electronic medical record allow comprehensive toxicity data to be recorded
      and analysed effortlessly. The average time taken to review these patients on a
      bi-weekly basis was 6.97 min and contained on average 60 words of toxicity
      description and action. CONCLUSION: Electronic toxicity scoring offers many
      advantages to the radiation oncology nurse, increased efficiency allows more
      frequent patient interaction which will in turn aid adherence. In order to better
      manage the treatment course of head and neck radiotherapy patients, nurses must
      be provided with streamlined and efficient electronic means of recording data. In
      this way it is possible to review head and neck radiotherapy patients bi-weekly.

PMID- 20678961
TI  - PBPC collections: Management, techniques and risks.
AB  - We evaluated the efficiency, safety and risks of three techniques which were used
      for autologous PBPC collections: (a) large-volume leukapheresis (LVL), (b)
      standard collections, and (c) a new modified technique which was named as "Mixed"
      collections. In spite of the fact that the standard and LVL collection techniques
      are used routinely, there may occur special conditions in which the procedures
      cannot be recommended. Some patients may suffer from serious clinical
      complications and they cannot tolerate either standard procedures with
      administration of higher doses of ACD-A, or the high extent of procedure in the
      course of LVL. We tried to find the safe and efficient collection technique which
      could help this group of patients to overcome their problems. The "Mixed"
      collection technique could be such a choice. The numbers of 136 autologous PBPC
      collections were performed in 98 patients who suffered from hemato-oncological
      diseases. We evaluated the results of (a) 93 LVL (more than 3 TBV, total blood
      volumes of the patients were processed; anticoagulation: ACD-A and Heparin), (b)
      16 Standard procedures (less than 3 TBV were processed; anticoagulation: ACD-A),
      and (c) 27 "Mixed" collections (less than 3 TBV of patients were processed;
      anticoagulation: ACD-A+ Heparin). Collections were performed by the use of
      separator Cobe Spectra, Caridian. In patients (a) with a good effect of
      mobilization (precollection CD 34+ cells in blood higher than 20*10(3)/mL) we
      prepared almost the same median dose of CD 34+ cells from the standard and
      "Mixed" collections, 3.8 and 4*10(6)/kg, respectively. In LVL the median yield of
      CD 34+ cells was 8.2*10(6)/kg. In patients (b) who were mobilized weakly
      (precollection CD 34+ cells in blood lower than 20*10(3)/mL), LVL enabled to
      prepare 1.5*10(6) of CD 34+/kg from one collection, while the median yield of CD
      34+ cells from the standard and "Mixed" collections was 0.9 and 1.2*10(6)/kg. All
      the standard, LVL and "Mixed" procedures were tolerated well without any serious
      adverse reactions. We detected 22 adverse reactions, but only three reactions
      were associated directly with the procedure. Mild hypocalcemia (2) and
      hypotensive reaction (1) were transient and treated efficiently. Procedures could
      continue and were finished according to the planned programme. Other reactions
      were related either to the insufficient function of central venous catheter or to
      the poor clinical condition of the patients. LVL enabled to get a higher yield of
      CD 34+ cells than the Standard and "Mixed" collections in well mobilized patients
      as well as in weakly mobilized patients. We observed the similar efficiency in
      standard and "Mixed" collections in well mobilized and weakly mobilized patients.
      We can recommend LVL in all patients who can tolerate it due to a greater chance
      of collecting higher yields of progenitor cells. In the weakly mobilized patients
      LVL offers a greater chance of collecting at least a minimum amount of CD 34+
      cells needed for transplantation. "Mixed" collections may be used as an
      alternative technique under the circumstances in which standard or LVL cannot be
      recommended - like in patients who do not tolerate a high amount of citrate or a
      high extent of the procedure, e.g. patients with cardiac arrhytmia, impaired
      liver or renal function or unstable vital signs.

PMID- 20678962
TI  - Targeted cellular immunotherapy for leukemia patients.
AB  - Leukemia-associated antigens (LAAs) which are differentially expressed by
      leukemic blasts constitute an aim for targeted therapies such as adoptive
      specific T lymphocytes. Several LAAs have been identified that elicit both
      cellular and serological immune responses in leukemia patients. CD8(+) T cells
      expressing a particular T cell receptor (TCR) are able to recognize such LAAs.
      They can be selected by streptamers and subsequently get infused into leukemia
      patients. These cells have the potential to lyse leukemic blasts. Streptamers
      constitute the only good manufacturing practice (GMP)-certified technology, which
      is available up to date for antigen-specific T cell sorting. Adoptive T cell
      transfer can restore the antigen-specific immune response in immunocompromised
      patients.

PMID- 20678963
TI  - The use of adjuvant high-dose-rate breast brachytherapy in patients with collagen
      vascular disease: a collaborative experience.
AB  - PURPOSE: To analyze toxicity and cosmesis in patients with collagen vascular
      disease (CVD) treated with accelerated partial breast irradiation (APBI) via high
      dose-rate (HDR) brachytherapy. METHODS AND MATERIALS: This is a pooled analysis
      of patients with early stage and in situ breast cancer with CVD treated with
      adjuvant multicatheter or balloon brachytherapy. Physicians at multiple
      institutions were asked to review their experience and report data regarding
      toxicity and cosmesis in patients with CVD. All patients fit American Society of
      Breast Surgeons recommendations for APBI and were treated with HDR brachytherapy
      with >= 3 months followup. RESULTS: Nine cases from five institutions are the
      subject of this analysis. The median patient age was 54 years and median followup
      was 31 months. All patients had documented history and active signs/symptoms of
      rheumatoid arthritis, systemic lupus erythematosis, psoriatic arthritis, or
      scleroderma. All patients had received medical therapy for CVD in the past, and
      78% were under active treatment at the time of brachytherapy. All the patients
      were treated with multicatheter or balloon (MammoSite [Hologic, Inc., Marlboro,
      MA], MammoSite ML [Hologic, Inc., Marlboro, MA], or Contura [Senorx, Irvine, CA])
      brachytherapy with a median volume of 45.5 cc and a median skin distance of
      7.5mm. Acute toxicity included Grade 1 skin erythema (5) and catheter-site wound
      dehiscence (1). Late toxicity included seroma (5), induration (5), pain (2),
      telangectasia (2), and superficial infection (1). Cosmesis was excellent or good
      for all the patients. CONCLUSIONS: Women with CVD have a toxicity and cosmesis
      profile consistent with other APBI series. Although confirmatory data is needed,
      it may not be necessary to exclude these patients from clinical trials of APBI.

PMID- 20678964
TI  - Laparoscopic revision of gastrojejunostomy revision with truncal vagotomy for
      persistent marginal ulcer after Roux-en-Y gastric bypass.

PMID- 20678965
TI  - Laparoscopic conversion of eroded adjustable gastric band to vertical sleeve
      gastrectomy.

PMID- 20678966
TI  - Pancreatic islet isolation after gastric bypass in a rat model: technique and
      initial results for a promising research tool.
AB  - BACKGROUND: Roux-en-Y gastric bypass (RYGB) affords a high remission rate of type
      2 diabetes mellitus among morbidly obese diabetic patients. We report the use of
      the isolated islet technique to assess pancreatic function and glucoregulatory
      mechanisms after RYGB surgery. METHODS: A total of 15 adult, male, Sprague Dawley
      diet-induced obese rats were randomly divided into 3 experimental groups: sham,
      RYGB, and pair-fed, with 5 rats in each group. The body weight was measured at
      baseline and every week for 4 weeks. Pancreatic islet function was assessed in
      vitro according to the amount of insulin secreted from isolated islets incubated
      in 2 mM and 20 mM glucose for 1 hour at 37  degrees C. Fasting plasma glucose,
      insulin, glucagon-like peptide-1, PYY3-36, and glucose-dependent insulinotropic
      peptide were measured at baseline and 28 days after surgery. RESULTS: The
      baseline body weight was 917 +/- 61, 831 +/- 42, and 927 +/- 43 g for the sham,
      RYGB, and pair-fed groups, respectively. The RYGB group lost 32% body weight
      compared with 16% for the sham and 24% for the pair-fed groups. Glucose
      stimulated insulin secretion from the isolated islets in the RYGB group was
      greater than in the comparison groups (P = .04) at 4 weeks after surgery. Fasting
      plasma glucagon-like peptide-1 and PYY3-36 were significantly increased at 4
      weeks in the RYGB group. CONCLUSION: Islet isolation and stimulation in the
      present animal model was feasible, affords a direct measurement of pancreatic
      islet function, and might provide a useful tool to study the effects of RYGB on
      pancreatic function and the relationship between islet cell function and incretin
      production after bariatric surgery.

PMID- 20678967
TI  - Body mass index-independent inflammation in omental adipose tissue associated
      with insulin resistance in morbid obesity.
AB  - BACKGROUND: Obesity is a strong risk factor for resistance to insulin-mediated
      glucose disposal, a precursor of type 2 diabetes and other disorders. However,
      not all obese individuals are insulin resistant. We sought to identify the
      molecular pathways that might cause obesity-associated insulin resistance in
      humans by studying the morbidly obese who were insulin sensitive versus insulin
      resistant, thereby eliminating obesity as a variable. METHODS: Combining gene
      expression profiling with computational approaches, we determined the global gene
      expression signatures of omental and subcutaneous adipose tissue samples obtained
      from similarly obese patients undergoing gastric bypass surgery. RESULTS: Gene
      sets related to chemokine activity and chemokine receptor binding were identified
      as most highly expressed in the omental tissue from insulin-resistant compared
      with insulin-sensitive subjects, independent of the body mass index. These
      upregulated genes included chemokines (C-C motif) ligand 2, 3, 4, and 18 and
      interleukin-8/(CC-X motif) ligand 8 and were not differentially expressed in the
      subcutaneous adipose tissues between the 2 groups of subjects. Insulin
      resistance, but not the body mass index, was associated with increased macrophage
      infiltration in the omental adipose tissue, as was adipocyte size, in these
      morbidly obese subjects. CONCLUSION: Our findings have demonstrated that
      inflammation of the omental adipose tissue is strongly associated with insulin
      resistance in human obesity even in subjects with similar body mass index values.

PMID- 20678968
TI  - Changes in depressive symptoms among adolescent bariatric candidates from
      preoperative psychological evaluation to immediately before surgery.
AB  - BACKGROUND: The preoperative psychological evaluation (including the assessment
      of depressive symptoms) is an important component in determining adolescent
      bariatric candidacy. The adult bariatric data have suggested that candidates can
      engage in "impression management" and underreport depressive symptoms during
      their preoperative evaluation. The present study examined whether adolescent
      depressive symptoms among bariatric candidates change during preoperative
      preparation compared with adolescents with extreme obesity who were not seeking
      surgery. METHODS: Adolescent candidates for bariatric surgery (n = 30; 60%
      female; mean age 16.5 +/- 1.4 years) completed the Beck Depression Inventory-II
      (BDI-II) at initial consultation (time 1, mean body mass index [BMI] 64.5 +/-
      11.5 kg/m(2)) and again immediately preoperatively (time 2, mean interval 4.7 +/-
      2.9 months; mean BMI 64.4 +/- 10.4 kg/m(2)). Comparators (n = 25; 64% female;
      mean age 16.2 +/- 1.2 years; mean BMI 46.5 +/- 4.8 kg/m(2)) were studied at
      enrollment in a research protocol and again 6 months later (mean interval 6.2 +/-
      0.4 months; mean BMI 46.8 +/- 5.0 kg/m(2)). The height and weight were also
      taken. RESULTS: We found a small, but statistically significant, difference in
      the BDI-II scores at time 1, with bariatric candidates reporting greater
      depressive symptoms (mean 16.6 +/- 12.9) than the comparators (mean 10.6 +/- 9.0;
      P < .05). No difference was seen in the BDI-II scores between the bariatric
      candidates (mean 14.4 +/- 12.1) and the comparators (mean 10.4 +/- 8.2) at time 2
      (P = .17). The change in BDI-II scores for the bariatric candidates showed a
      trend toward significance (P = .09). CONCLUSION: These results reinforce the
      position that the adult bariatric literature does not necessarily generalize to
      the adolescent bariatric population. They further suggest that impression
      management might not be a significant concern in the assessment of adolescent
      bariatric candidates. Future research should examine whether preoperative changes
      in psychological functioning predict the postoperative outcomes.

PMID- 20678969
TI  - Significant resolution of female sexual dysfunction after bariatric surgery.
AB  - BACKGROUND: We have previously reported that most women seeking bariatric surgery
      have had female sexual dysfunction (FSD) as defined by the validated Female
      Sexual Function Index (FSFI). The present study examined whether FSD resolves
      after bariatric surgery. METHODS: A total of 54 reportedly sexually active women
      (43.3 +/- 9.5 years) completed the FSFI preoperatively and 6 months
      postoperatively after a mean percentage of excess weight loss of 42.3%
      (laparoscopic adjustable gastric banding [n = 38], percentage of excess weight
      loss, 34.6% +/- 15.7%; Roux-en-Y gastric bypass [n = 16], percentage of excess
      weight loss 60.0% +/- 21.2%). The FSFI assesses sexual function across 6 domains,
      with higher scores indicating better sexual function. The summing of these scores
      yields a FSFI total score (range 2-36, with a score of <= 26.55 indicating FSD).
      RESULTS: Before surgery, 34 women (63%) had scores indicative of FSD. By 6 months
      postoperatively, the FSD had resolved in 23 (68%) of these 34 women, and only 1
      woman had developed FSD postoperatively. In the entire sample, significant (P <
      .05) improvements occurred from before to after surgery on all FSFI domains. The
      FSFI total scores improved after laparoscopic adjustable gastric banding (from
      24.2 +/- 5.9 to 29.1 +/- 4.1, P < .001) and Roux-en-Y gastric bypass (from 23.7
      +/- 7.7 to 30.0 +/- 4.7, P < .001). In regression analyses, being married,
      younger age, and worse preoperative sexual function were related to greater
      sexual function improvements. Postoperatively, the participants' FSFI total
      scores were indistinguishable from those of published normative controls (29.4 +/
      4.3 versus 30.5 +/- 5.3, P = .18). CONCLUSION: FSD resolved in a large
      percentage of women after bariatric surgery. Sexual functioning in the entire
      sample improved to levels consistent with those of normative controls. This
      improvement in sexual function did not depend on surgery type or weight loss
      amount and appears to be an additional benefit for women undergoing bariatric
      surgery.

PMID- 20678970
TI  - Laparoscopic pancreatoduodenectomy after laparoscopic gastric bypass.

PMID- 20678971
TI  - Laparoscopic conversion of sleeve gastrectomy to Roux-en-Y gastric bypass for
      acute gastric outlet obstruction after laparoscopic sleeve gastrectomy for morbid
      obesity.

PMID- 20678973
TI  - [Scrotal migration of ventriculoperitoneal shunts].

PMID- 20678972
TI  - 6-Vinyl coenzyme Q0: Electropolymerization and electrocatalysis of NADH oxidation
      exploiting poly-p-quinone-modified electrode surfaces.
AB  - 6-Vinyl coenzyme Q(0) serves as a convenient starting material for the formation
      of electropolymerized coenzyme Q(0) on glassy carbon electrodes and the modified
      electrodes displays electrocatalytic activity toward NADH (beta-nicotinamide
      adenine dinucleotide) oxidation. The detection of NADH was measured by
      differential pulse voltammetry, which reveals that the peak current is linear to
      the concentration of NADH within the range of 10-100MUM. This would be helpful
      for the understanding of the interaction between coenzyme Q(0) and NADH in the
      biological process.

PMID- 20678974
TI  - [Refractory Kawasaki disease with coronary aneurysms treated with infliximab].
AB  - The classic treatment of Kawasaki disease with immunoglobulin and acetyl
      salicylic acid obtains a good response in 90% of patients, decreasing the risk of
      coronary involvement. However, in patients that do not respond to immunoglobulin,
      it is not clear which therapy should be used: other doses of immunoglobulin,
      corticosteroids or infliximab. Infliximab is becoming an important second line
      treatment for Kawasaki refractory to immunoglobulin, although there are few
      studies and clinical reports with this drug. We present a 5 months-old infant
      with refractory Kawasaki disease who developed coronary aneurysms despite two
      immunoglobulin doses and three intravenous pulses-doses of corticosteroids. The
      infant was finally treated with a single dose of infliximab with good clinical
      progress.

PMID- 20678975
TI  - [The choking game: a potentially lethal game].
AB  - Choking games are a known behaviour among adolescents, although they have not
      been reported in the Spanish scientific literature. They are games which seek a
      brief euphoria due to the restriction oxygen flow into the brain. The case of a
      15 year-old adolescent boy who died in a room due to accidental hanging while
      playing the choking game is presented. Case characteristics are described and
      literature reviewed. The choking game is a dangerous and potentially fatal
      activity. Cases like the one described may be helpful for paediatricians and
      physicians in recognising this phenomenon and its risks. Knowledge of this
      activity is important for the prevention and early detection of adolescents risk
      behaviours.

PMID- 20678976
TI  - Corticoperiosteal flap in the treatment of nonunions and small bone gaps:
      technical details and expanding possibilities.
AB  - The corticoperiosteal flap from the medial femoral condyle (CP) has proved to be
      highly reliable in the management of persistent, recurrent nonunion. However,
      much of the related literature has focussed on the flap aspects of the procedure
      and not so much on bone work-up. We present a series of 25 patients with
      nonunions and small bone gaps irresponsive to conventional therapy that were
      successfully treated with a CP with/without the addition of non-vascularised bone
      graft from the iliac crest. Different technical options of bone reconstruction
      are possible and discussed: CP plus non-structural bone chips, CP plus structural
      bi/tricortical struts or CP plus vascularised cancellous bone from the femoral
      condyle. A stable internal fixation was performed in all cases. Clinical and
      radiological evidence of healing was obtained in all the patients. Donor-site
      complications were few and transient (suture intolerance, seroma and numbness in
      the saphenous territory). No fracture of the femur, knee instability or stiffness
      has been observed. The corticoperiosteal flap from the femoral condyle is an
      excellent source of vascularisation and osteogenic stimulus to the nonunion site
      and highly effective in the management of persistent nonunions and small bone
      gaps. When needed, a structural corticocancellous strut from the iliac crest
      (along with a stable internal fixation) provides the greatest stability and the
      possibility of a prompt rehabilitation and functional recovery. The
      corticoperiosteal flap has succeeded in revascularising these highly demanding
      grafts and in allowing a 100% union rate.

PMID- 20678977
TI  - Different domains of C. elegans PAR-3 are required at different times in
      development.
AB  - Polarity is a fundamental cellular feature that is critical for generating cell
      diversity and maintaining organ functions during development. In C. elegans, the
      one-cell embryo is polarized via asymmetric localization of the PAR proteins,
      which in turn are required to establish the future anterior-posterior axis of the
      embryo. PAR-3, a conserved PDZ domain-containing protein, acts with PAR-6 and PKC
      3 (atypical protein kinase; aPKC) to regulate cell polarity and junction
      formation in a variety of cell types. To understand how PAR-3 localizes and
      functions during C. elegans development, we produced targeted mutations and
      deletions of conserved domains of PAR-3 and examined the localization and
      function of the GFP-tagged proteins in C. elegans embryos and larvae. We find
      that CR1, the PAR-3 self-oligomerization domain, is required for PAR-3 cortical
      distribution and function only during early embryogenesis and that PDZ2 is
      required for PAR-3 to accumulate stably at the cell periphery in early embryos
      and at the apical surface in pharyngeal and intestinal epithelial cells. We also
      show that phosphorylation at S863 by PKC-3 is not essential in early
      embryogenesis, but is important in later development. Surprisingly neither PDZ1
      nor PDZ3 are essential for localization or function. Our results indicate that
      the different domains and phosphorylated forms of PAR-3 can have different roles
      during C. elegans development.

PMID- 20678978
TI  - Induction of human keratinocytes into enamel-secreting ameloblasts.
AB  - Mammalian tooth development relies heavily on the reciprocal and sequential
      interactions between cranial neural crest-derived mesenchymal cells and stomadial
      epithelium. During mouse tooth development, odontogenic potential, that is, the
      capability to direct an adjacent tissue to form a tooth, resides in dental
      epithelium initially, and shifts subsequently to dental mesenchyme. Recent
      studies have shown that mouse embryonic dental epithelium possessing odontogenic
      potential is able to induce the formation of a bioengineered tooth crown when
      confronted with postnatal mesenchymal stem cells of various sources. Despite many
      attempts, however, postnatal stem cells have not been used successfully as the
      epithelial component in the generation of a bioengineered tooth. We show here
      that epithelial sheets of cultured human keratinocytes, when recombined with
      mouse embryonic dental mesenchyme, are able to support tooth formation. Most
      significantly, human keratinocytes, recombined with mouse embryonic dental
      mesenchyme in the presence of exogenous FGF8, are induced to express the dental
      epithelial marker PITX2 and differentiate into enamel-secreting ameloblasts that
      develop a human-mouse chimeric whole tooth crown. We conclude that in the
      presence of appropriate odontogenic signals, human keratinocytes can be induced
      to become odontogenic competent; and that these are capable of participating in
      tooth crown morphogenesis and differentiating into ameloblasts. Our studies
      identify human keratinocytes as a potential cell source for in vitro generation
      of bioengineered teeth that may be used in replacement therapy.

PMID- 20678979
TI  - The nuclear receptor gene nhr-25 plays multiple roles in the Caenorhabditis
      elegans heterochronic gene network to control the larva-to-adult transition.
AB  - Developmental timing in the nematode Caenorhabditis elegans is controlled by
      heterochronic genes, mutations in which cause changes in the relative timing of
      developmental events. One of the heterochronic genes, let-7, encodes a microRNA
      that is highly evolutionarily conserved, suggesting that similar genetic pathways
      control developmental timing across phyla. Here we report that the nuclear
      receptor nhr-25, which belongs to the evolutionarily conserved fushi tarazu
      factor 1/nuclear receptor NR5A subfamily, interacts with heterochronic genes that
      regulate the larva-to-adult transition in C. elegans. We identified nhr-25 as a
      regulator of apl-1, a homolog of the Alzheimer's amyloid precursor protein-like
      gene that is downstream of let-7 family microRNAs. NHR-25 controls not only apl-1
      expression but also regulates developmental progression in the larva-to-adult
      transition. NHR-25 negatively regulates the expression of the adult-specific
      collagen gene col-19 in lateral epidermal seam cells. In contrast, NHR-25
      positively regulates the larva-to-adult transition for other timed events in seam
      cells, such as cell fusion, cell division and alae formation. The genetic
      relationships between nhr-25 and other heterochronic genes are strikingly varied
      among several adult developmental events. We propose that nhr-25 has multiple
      roles in both promoting and inhibiting the C. elegans heterochronic gene pathway
      controlling adult differentiation programs.

PMID- 20678981
TI  - Perceptual organization and visual search processes during target detection task
      performance in schizophrenia, as revealed by fMRI.
AB  - BACKGROUND: Past studies of perceptual organization in schizophrenia have
      demonstrated impairments binding fragmented stimulus components into unified
      representations. ERP and fMRI data indicate that even under conditions of
      adequate behavioral task performance, significant and meaningful changes in
      cortical and subcortical activation are present. Here, we examined, using fMRI,
      activation differences on a visual task wherein feature grouping was a precursor
      to the formation of distinct groups in the service of target location and
      identification. METHOD: Fourteen schizophrenia patients and 16 healthy controls
      completed a target detection task with 2 conditions: one in which target
      distractor grouping facilitates detection (the Isolated condition) and one in
      which it hinders detection (the Embedded condition). Stimuli were blocked by
      condition. Accuracy and RT data were obtained in addition to fMRI data. RESULTS:
      Patients and controls did not differ significantly in accuracy or RT in either
      condition. Within this context, controls demonstrated greater recruitment of
      brain regions involved in visual-spatial processing, and the groups differed in
      activity in areas known to support visual search, visual analysis, decision
      making and response generation. CONCLUSION: These findings are consistent with
      past data indicating reduced processing of stimulus organization, and the
      subsequent use of inefficient visual search strategies, even under conditions
      when behavioral performance is at a high level and matches that of healthy
      controls.

PMID- 20678982
TI  - Affective processing of loved faces: contributions from peripheral and central
      electrophysiology.
AB  - Research on the neural mechanisms of face identity constitutes a fruitful method
      to explore the affective contributions to face processing. Here, we investigated
      central and peripheral electrophysiological indices associated with the
      perception of loved faces. Subjects viewed black-and-white photographs of faces
      that belonged to one of five categories: loved ones, famous people, unknown
      people, babies, and neutral faces from the Eckman and Friesen system.
      Subcategories of loved faces included romantic partner, parents, siblings, second
      degree relatives, and friends. Pictures were presented in two separate blocks,
      differing in viewing time (0.5s vs. 4s), inter-stimulus interval (1.2s vs. 18s),
      and number of face presentations (200 vs. 50). Heart rate, skin conductance,
      electromyography of the zygomatic muscle, and event-related potentials (ERPs)
      were obtained while participants passively viewed the pictures. Subjective
      picture ratings of valence, arousal, and dominance were obtained at the end of
      the experiment. Both central and peripheral electrophysiological measures
      differentiated faces of loved ones from all other categories by eliciting higher
      heart rate, skin conductance, and zygomatic activity, as well as larger
      amplitudes of the late ERP components P3 and LPP. Loved faces also resulted in
      higher valence and arousal, but lower dominance ratings. Additional differences
      were found among subcategories of loved faces. Faces of romantic partners
      elicited higher physiological (skin conductance and zygomatic activity) and
      subjective (emotional arousal) responses than parents, siblings, or friends,
      suggesting that looking at the image of someone we love evokes strong positive
      affect and emotional/cognitive arousal that go beyond a feeling of familiarity or
      simple recognition.

PMID- 20678980
TI  - Emotion recognition following pediatric traumatic brain injury: longitudinal
      analysis of emotional prosody and facial emotion recognition.
AB  - Children with closed head injuries often experience significant and persistent
      disruptions in their social and behavioral functioning. Studies with adults
      sustaining a traumatic brain injury (TBI) indicate deficits in emotion
      recognition and suggest that these difficulties may underlie some of the social
      deficits. The goal of the current study was to examine if children sustaining a
      TBI exhibit difficulties with emotion recognition in terms of emotional prosody
      and face emotion recognition and to determine (1) how these abilities change over
      time and (2) what, if any, additional factors such as sex, age, and socioeconomic
      status (SES) affected the findings. Results provide general support for the idea
      that children sustaining a TBI exhibit deficits in emotional prosody and face
      emotion recognition performance. Further, although some gains were noted in the
      TBI group over the two-years following injury, factors such as SES and age at
      injury influenced the trajectory of recovery. The current findings indicate the
      relationship between TBI and emotion recognition is complex and may be influenced
      by a number of developmental and environmental factors. Results are discussed in
      terms of their similarity to previous investigations demonstrating the influence
      of environmental factors on behavioral recovery following pediatric TBI, and with
      regard to future investigations that can further explore the link between emotion
      recognition deficits and long-term behavioral and psychosocial recovery.

PMID- 20678983
TI  - The C-terminal coiled-coil of the bacterial voltage-gated sodium channel NaChBac
      is not essential for tetramer formation, but stabilizes subunit-to-subunit
      interactions.
AB  - The NaChBac is a prokaryotic homologue of the voltage-gated sodium channel found
      in the genome of the alkalophilic bacterium Bacillus halodurans C-125. Like a
      repeating cassette of mammalian sodium channel, the NaChBac possesses hydrophobic
      domains corresponding to six putative transmembrane segments and a pore loop, and
      exerts channel function by forming a tetramer although detailed mechanisms of
      subunit assembly remain unclear. We generated truncated mutants from NaChBac, and
      investigated their ability to form tetramers in relation to their channel
      functions. A mutant that deletes almost all of the C-terminal coiled-coil
      structure lost its voltage-dependent ion permeability, although it was properly
      translocated to the cell surface. The mutant protein was purified as a tetramer
      using a reduced concentration of detergent, but the association between the
      subunits was shown to be much weaker than the wild type. The chemical cross
      linking, blue native PAGE, sedimentation velocity experiments, size exclusion
      chromatography, immunoprecipitation, and electron microscopy all supported its
      tetrameric assembly. We further purified the C-terminal cytoplasmic domain alone
      and confirmed its self-oligomerization. These data suggest that the C-terminal
      coiled-coil structure stabilizes subunit-to-subunit interactions of NaChBac, but
      is not critical for their tetramer formation.

PMID- 20678984
TI  - Basic operations in working memory: contributions from functional imaging
      studies.
AB  - Working memory (WM) constitutes a fundamental aspect of human cognition. It
      refers to the ability to keep information active for further use, while allowing
      it to be prioritized, modified and protected from interference. Much research has
      addressed the storage function of WM, however, its 'working' aspect still remains
      underspecified. Many operations that work on the contents of WM do not appear
      specific to WM. The present review focuses on those operations that we consider
      "basic" because they operate in the service of memory itself, by providing its
      basic functionality of retaining information active, in a stable yet flexible
      way. Based on current process models of WM we review five strands of research:
      (1) mnemonic selection of one item amongst others, (2) updating the focus of
      attention with the selected item, (3) updating the content of visual WM with new
      item(s), (4) rehearsal of visuospatial information and (5) coping with
      interference. We discuss the neuronal substrates underlying those operations
      obtained with functional magnetic resonance imaging and relate them to findings
      on "executive functions". The presented data support the view that WM emerges
      from interactions between higher sensory, attentional and mnemonic functions,
      with separable neural bases. However, interference processing and the
      representation of rule switching in WM may demand an extension of the current WM
      models by executive control functions.

PMID- 20678985
TI  - Sexual or paternal experiences alter alloparental behavior and the central
      expression of ERalpha and OT in male mandarin voles (Microtus mandarinus).
AB  - Various hypotheses have been proposed to explain factors influencing male
      alloparental behavior in cooperatively breeding species. Mandarin voles (Microtus
      mandarinus) are ideal animal models to investigate these factors because they are
      highly social rodents and display biparental care and spontaneous parental care
      when exposed to foster pups. Here we test the idea that the sexual and paternal
      experience of males influences alloparental behavior toward novel pups, and that
      these experiences alter the expression of neuropeptide oxytocin (OT) and estrogen
      receptor alpha (ERalpha). Alloparental behavior and OT and ERalpha expression
      were compared between virgin males that had no prior sexual or reproductive
      experience, exposed males that with prior exposure to novel pups before the test,
      paired males that had been housed with a female, and new fathers having their
      first litter with a female. Our results show that prior exposure to novel pups
      and prior mating and paternal experience increased male alloparental behavior
      toward a novel pup. This experience also increased OT expression and affected the
      expression of ERalpha. This study reveals important initiation factors for male
      alloparental behavior and suggests a relationship between alloparental behavior
      and central OT expression in males.

PMID- 20678987
TI  - Neonatal gastrin-releasing peptide receptor blockade reduces maternal odor
      preference in rats.
AB  - Alterations in attachment behavior might play a role in the dysfunction in social
      behavior displayed by autistic infants. Here we show that neonatal gastrin
      releasing peptide receptor (GRPR) blockade induces a reduction in maternal odor
      preference, a task involving attachment behavior, in infant rats. These findings
      provide the first evidence that the GRPR regulates odor preference, supporting
      the view that the GRPR is involved in attachment and social behaviors.

PMID- 20678986
TI  - Ventromedial and medial preoptic hypothalamic ibotenic acid lesions potentiate
      systemic morphine analgesia in female, but not male rats.
AB  - Sex differences in systemic morphine analgesia occur with male rodents displaying
      significantly greater analgesic magnitudes and potencies than females. Neonatal
      androgenization, and to a lesser degree, adult ovariectomy enhance systemic
      morphine analgesia in female rats, implicating both organizational and
      activational effects of gonadal hormones. The neuroanatomical circuits sensitive
      to sex-related hormones by which females display a smaller opiate analgesic
      effect is not clear, but the ventromedial (VMH) and medial preoptic (MPOA)
      hypothalamic nuclei are critical in the monitoring of estradiol and other sex
      hormone levels. To assess the contribution of these nuclei to sex and adult
      gonadectomy differences in systemic morphine analgesia, intact male, intact
      female and adult ovariectomized (OVEX) female rats received bilateral saline
      (SAL) or ibotenic acid (IBO) microinjections into either the VMH or MPOA.
      Following surgeries, baseline tail-flick latencies over 120 minutes (min) were
      assessed over 4 days in all nine groups with intact females tested in the estrus
      phase of their cycle. All animals then received an ascending series of morphine
      (1.0, 2.5, 5.0, 7.5, 10.0mg/kg) injections 30min prior to the tail-flick test
      time course with 8-12 day inter-injection intervals between doses. Baseline
      latencies failed to differ between SAL-treated intact males and females, but were
      significantly higher in SAL-treated OVEX females. Both VMH IBO and MPOA IBO
      lesions increased baseline latencies in intact male and female rats, but not in
      OVEX females. SAL-treated intact males (ED(50)=4.0mg/kg) and SAL-treated OVEX
      females (ED(50)=3.5mg/kg) displayed significantly greater potencies of systemic
      morphine analgesia than SAL-treated intact females (ED(50)=6.3mg/kg), confirming
      previous gender and gonadectomy differences. Neither VMH IBO (ED(50)=3.7 mg/kg)
      nor MPOA IBO (ED(50)=4.1mg/kg) males differed from SAL-treated males in the
      potency of systemic morphine analgesia. In contrast, VMH IBO (ED(50)=4.1mg/kg)
      and MPOA IBO (ED(50)=3.5mg/kg) intact females displayed significantly greater
      potencies in systemic morphine analgesia than SAL-treated intact females.
      However, VMH IBO OVEX (ED(50)=3.5mg/kg) and MPOA IBO OVEX (ED(50)=3.9 mg/kg)
      failed to differ from SAL-treated OVEX females in the potency of systemic
      morphine analgesia. The magnitudes of systemic morphine analgesia as measured by
      Maximum Percentage Effect values displayed similar patterns, but lesser degrees,
      of effects. These data suggest that VMH and MPOA nuclei act to tonically inhibit
      endogenous pain-inhibitory circuits in the intact female, but not intact male
      brain, and that removal of circulating gonadal hormones by OVEX and/or
      excitotoxic destruction of these estrogen receptor accumulating nuclei disinhibit
      the female analgesic response to systemic morphine.

PMID- 20678988
TI  - Effect of controlled laser microporation on drug transport kinetics into and
      across the skin.
AB  - The objectives of this study were to investigate a novel laser microporation
      technology ( P.L.E.A.S.E. Painless Laser Epidermal System) and to determine the
      effect of pore number and depth on the rate and extent of drug delivery across
      the skin. In addition, the micropores were visualized by confocal laser scanning
      microscopy and histological studies were used to determine the effect of laser
      fluence (energy applied per unit area) on pore depth. Porcine ear skin was used
      as the membrane for both the pore characterization and drug transport studies.
      Confocal images in the XY-plane revealed that the pores were typically 150-200
      microm in diameter. Histological sections confirmed that fluence could be used to
      effectively control pore depth - low energy application (4.53 and 13.59 J/cm(2))
      resulted in selective removal of the stratum corneum (20-30 microm), intermediate
      energies (e.g., 22.65 J/cm(2)) produced pores that penetrated the viable
      epidermis (60-100 microm) and higher application energies created pores that
      reached the dermis (>150-200 microm). The effects of pore number and pore depth
      on molecular transport were quantified by comparing lidocaine delivery kinetics
      across intact and porated skin samples. After 24h, cumulative skin permeation of
      lidocaine with 0 (control), 150, 300, 450 and 900 pores was 107+/-46, 774+/-110,
      1400+/-344, 1653+/-437 and 1811+/-642 microg/cm(2), respectively; there was no
      statistically significant difference between 300, 450 and 900 pore data -
      probably due to the effect of drug depletion since >50% of the applied dose was
      delivered. Importantly, increasing fluence did not produce a statistically
      significant increase in lidocaine permeation; after 24h, cumulative lidocaine
      permeation was 1180+/-448, 1350+/-445, 1240+/-483 and 1653+/-436 microg/cm(2) at
      fluences of 22.65, 45.3, 90.6 and 135.9 J/cm(2), respectively. Thus, shallow
      pores were equally effective in delivering lidocaine. Increasing lidocaine
      concentration in the formulation from 10 to 25mg/ml produced a corresponding
      increase in permeation (at 24h, 1650+/-437 and 4005+/-1389 microg/cm(2),
      respectively). The validity of the porcine skin model was confirmed as transport
      across porcine and human skins was shown to be statistically equivalent (at 24h,
      1811+/-642 and 2663+/-208 microg/cm(2), respectively). The clinical potential of
      the technology and its capacity to provide significantly faster delivery than
      conventional passive administration was demonstrated in short duration
      experiments involving application of a marketed lidocaine cream (LMX4) to laser
      porated skin; after only 5 min of formulation application, lidocaine deposition
      was measured at 61.3+/-7.5 microg/cm(2). In conclusion, the results demonstrate
      the ability of P.L.E.A.S.E.(R) (i) to create well-defined conduits in the skin,
      (ii) to provide a controlled enhancement of transdermal transport and (iii) to
      enable improvement in both the rate and extent of drug delivery.

PMID- 20678990
TI  - In vitro and in vivo gene delivery mediated by Lactosylated dendrimer/alpha
      cyclodextrin conjugates (G2) into hepatocytes.
AB  - The purpose of this study is to evaluate in vitro and in vivo gene delivery
      efficiency of polyamidoamine (PAMAM) starburst dendrimer (generation 2, G2)
      conjugates with alpha-cyclodextrin (alpha-CDE (G2)) bearing lactose (Lac-alpha
      CDE) with various degrees of substitution of the lactose moiety (DSL) as a novel
      hepatocyte-selective carrier in hepatocytes. Lac-alpha-CDE (DSL 2.6) was found to
      have much higher gene transfer activity than dendrimer, alpha-CDE, Lac-alpha-CDE
      (DSL 1.2, 4.6, 6.2 and 10.2) and lactosylated dendrimer (Lac-dendrimer, DSL 2.4)
      in HepG2 cells, which are dependent on the expression of cell-surface
      asialoglycoprotein receptor (ASGP-R), reflecting the cellular association of the
      plasmid DNA (pDNA) complexes. The physicochemical properties of pDNA complex with
      Lac-alpha-CDE (DSL 2.6) were almost comparable to that with alpha-CDE. Lac-alpha
      CDE (DSL 2.6) provided negligible cytotoxicity up to a charge ratio of 150 in
      HepG2 cells. Lac-alpha-CDE (DSL 2.6) provided gene transfer activity higher than
      jetPEI-Hepatocyte to hepatocytes with much less changes of blood chemistry values
      12h after intravenous administration in mice. These results suggest the potential
      use of Lac-alpha-CDE (DSL 2.6) as a non-viral vector for gene delivery toward
      hepatocytes.

PMID- 20678991
TI  - Autonomic hyper-vigilance in post-infective fatigue syndrome.
AB  - This study examined whether post-infective fatigue syndrome (PIFS) is associated
      with a disturbance in bidirectional autonomic signalling resulting in heightened
      perception of symptoms and sensations from the body in conjunction with autonomic
      hyper-reactivity to perceived challenges. We studied 23 patients with PIFS and 25
      healthy matched control subjects. A heartbeat discrimination task and a pressure
      pain threshold test were used to assess interoceptive sensitivity. Cardiac
      response was assessed over a 4-min Stroop task. PIFS was associated with higher
      accuracy in heartbeat discrimination and a lower pressure pain threshold.
      Increased interoceptive sensitivity correlated strongly with current symptoms and
      potentiated differences in the cardiac response to the Stroop task, which in PIFS
      was characterized by insensitivity to task difficulty and lack of habituation.
      Our results provide the first evidence of heightened interoceptive sensitivity in
      PIFS. Together with the distinct pattern in cardiac responsivity these findings
      present a picture of physiological hyper-vigilance and response inflexibility.

PMID- 20678989
TI  - In vitro permeation of a pegylated naltrexone prodrug across microneedle-treated
      skin.
AB  - Microneedles (MN) are a useful tool for increasing skin permeability to
      xenobiotics. Previous research showed marked improvement in the percutaneous flux
      of naltrexone (NTX) hydrochloride by the use of MN skin pretreatment alone;
      however, for better therapeutic effect, further enhancement is desired. The goal
      of this in vitro study was to combine microneedle skin pretreatment with the use
      of a highly water-soluble PEGylated naltrexone prodrug (polyethyleneglycol-NTX,
      PEG-NTX) to investigate its transdermal transport at varying concentrations.
      Solubility and stability of the prodrug were investigated. In vitro diffusion
      experiments employing MN-treated minipig skin were used to evaluate the
      performance of the PEGylated prodrug. The results revealed substantial deviation
      from ideal behavior, with the flux through MN-treated skin having a nonlinear
      relationship to the prodrug concentration in the donor solution. While in the
      lower concentration range tested the prodrug flux increase was proportional to
      the concentration increase, at high concentrations it showed no such dependence.
      Accounting for the decrease in the effective prodrug diffusivity accompanying the
      increase in viscosity, as predicted by the Stokes-Einstein equation, provided a
      rationale for the observed flux values. Increasing the viscosity of the donor
      solution is hypothesized to afford a curvilinear permeation profile for the
      PEGylated NTX prodrug.

PMID- 20678992
TI  - Oxytocin not only increases trust when money is at stake, but also when
      confidential information is in the balance.
AB  - Past studies have suggested that the neuropeptide oxytocin (OT) could play a
      crucial role in human trusting behavior. Specifically, people on OT would be more
      willing to entrust someone with their money than would people on a placebo.
      Because alternative explanations-which do not involve trust-exist for these
      studies' findings, the present study aimed to rule out confounds and test how OT
      influences trust behavior in a totally different context. The variable at stake
      was not money but confidential information. Sixty participants were randomly
      assigned to receive either OT or a placebo. Results showed that oxytocin does
      increase trust, and that its effects extend beyond money. Specifically,
      participants on OT were 44 times more trusting that their privacy would not be
      violated than participants on placebo.

PMID- 20678993
TI  - A plasma membrane Ca2+ ATPase isoform at the postsynaptic density.
AB  - Most excitatory input in the hippocampus impinges on dendritic spines. Entry of
      Ca(2+) into spines through NMDA receptors can trigger a sequence of biochemical
      reactions leading to sustained changes in synaptic efficacy. To provide
      specificity, dendritic spines restrict the diffusion of Ca(2+) signaling and
      downstream molecules. The postsynaptic density (PSD) (the most prominent
      subdomain within the spine) is the site of Ca(2+) entry through NMDA receptors.
      We here demonstrate that Ca(2+) can also be removed via pumps embedded in the
      PSD. Using light- and electron-microscopic immunohistochemistry, we find that
      PMCA2w, a member of the plasma membrane Ca(2+)-ATPase (PMCA) family, concentrates
      at the PSD of most hippocampal spines. We propose that PMCA2w may be recruited
      into supramolecular complexes at the postsynaptic density, thus helping to
      regulate Ca(2+) nanodomains at subsynaptic sites. Taken together, these results
      suggest a novel function for PMCAs as modulators of Ca(2+) signaling at the
      synapse.

PMID- 20678995
TI  - ATP-mediated protein kinase B Akt/mammalian target of rapamycin mTOR/p70
      ribosomal S6 protein p70S6 kinase signaling pathway activation promotes
      improvement of locomotor function after spinal cord injury in rats.
AB  - The protein kinase B (Akt)/mammalian target of rapamycin (mTOR)/p70 ribosomal S6
      protein kinase (p70S6K) signaling pathway, as a central controller of cell
      growth, proliferation, survival, and differentiation in response to extracellular
      signals, growth factors, nutrient availability, energy status of the cell, and
      stress, has recently gained attention in neuroscience. The effects of this
      signaling pathway on repair of spinal cord injury (SCI), however, have not been
      well elucidated. ATP is increasingly recognized as an important regulator of
      signal transduction pathways, and plays important roles in functional recovery
      after nervous system injury. In the present study, we examined the ATP-induced
      changes of the Akt/mTOR/p70S6K signaling pathway in injured spinal cord of adult
      rats and potential therapeutic effects of this pathway on SCI-induced locomotor
      dysfunction. SCI was produced by extradural weight-drop using modified Allen's
      stall with damage energy of 50 g-cm force. The rats were divided into four
      groups: SCI plus ATP, SCI plus saline, SCI plus ATP and rapamycin, and sham
      operated. Using immunostaining studies, Western blot analyses and real-time
      qualitative RT-PCR analyses, we demonstrated that the Akt/mTOR/p70S6K signaling
      pathway is present in the injured spinal cord and the expression of its
      components at the protein and mRNA levels is significantly elevated by exogenous
      administration of ATP following SCI. We observed the effectiveness of the
      activated Akt/mTOR/p70S6K signaling pathway in improving locomotor recovery,
      significantly increasing the expression of nestin, neuronal nuclei (NeuN), neuron
      specific enolase (NSE), and neurofilament 200 (NF200), and relatively inhibiting
      excessive reactive astrogliosis after SCI in a rapamycin-sensitive manner. We
      concluded that ATP injection produced a significant activation of the
      Akt/mTOR/p70S6K signaling pathway in the injured spinal cord and that enhancement
      of rapamycin-sensitive signaling produces beneficial effects on SCI-induced motor
      function defects and repair potential. We suggest that modulation of this protein
      kinase signaling pathway activity should be considered as a potential therapeutic
      strategy for SCI.

PMID- 20678996
TI  - Region-specific projections from the subfornical organ to the paraventricular
      hypothalamic nucleus in the rat.
AB  - Neurons in the subfornical organ (SFO) project to the paraventricular
      hypothalamic nucleus (PVN) and there, in response to osmolar and blood pressure
      changes, regulate vasopressin neurons in the magnocellular part (mPVN) or neurons
      in the parvocellular part (pPVN) projecting to the cardiovascular center. The SFO
      is functionally classified in two parts, the dorsolateral peripheral (pSFO) and
      ventromedial core parts (cSFO). We investigated the possibility that neurons in
      each part of the SFO project region-specifically to each part of the PVN, using
      anterograde and retrograde tracing methods. Following injection of an anterograde
      tracer, biotinylated dextran amine (BDX) in the SFO, the respective numbers of
      BDX-uptake neurons in the pSFO and cSFO were counted and the ratio of the former
      to the latter was obtained. In addition, the respective areas occupied by BDX
      labeled axons per unit area of the mPVN and pPVN were measured and the ratio of
      the former to the latter was obtained. Similarly, following injection of the
      retrograde tracer in the PVN, the respective areas occupied by tracer per unit
      area of the mPVN and pPVN were measured and the ratio of the former to the latter
      was obtained. The respective numbers of retrogradely labeled neurons in the pSFO
      and cSFO were also counted and the ratio of the former to the latter was
      obtained. It became clear by statistical analyses that there are strong positive
      correlations between the ratio of BDX-uptake neuron number in the SFO and the
      ratio of BDX-axon area in the PVN in anterograde experiment (correlation
      coefficient: 0.787) and between the ratio of retrograde neuron number in the SFO
      and the ratio of tracer area in the PVN in retrograde experiment (correlation
      coefficient: 0.929). The result suggests that the SFO projects region
      specifically to the PVN, the pSFO to the mPVN and the cSFO to the pPVN.

PMID- 20678994
TI  - Steroid receptor coactivator-2 expression in brain and physical associations with
      steroid receptors.
AB  - Estradiol and progesterone bind to their respective receptors in the hypothalamus
      and hippocampus to influence a variety of behavioral and physiological functions,
      including reproduction and cognition. Work from our lab and others has shown that
      the nuclear receptor coactivators, steroid receptor coactivator-1 (SRC-1) and SRC
      2, are essential for efficient estrogen receptor (ER) and progestin receptor (PR)
      transcriptional activity in brain and for hormone-dependent behaviors. While the
      expression of SRC-1 in brain has been studied extensively, little is known about
      the expression of SRC-2 in brain. In the present studies, we found that SRC-2 was
      highly expressed throughout the hippocampus, amygdala and hypothalamus, including
      the medial preoptic area (MPOA), ventral medial nucleus (VMN), arcuate nucleus
      (ARC), bed nucleus of the stria terminalis, supraoptic nucleus and
      suprachiasmatic nucleus. In order for coactivators to function with steroid
      receptors, they must be expressed in the same cells. Indeed, SRC-2 and ER(alpha)
      were coexpressed in many cells in the MPOA, VMN and ARC, all brain regions known
      to be involved in female reproductive behavior and physiology. While in vitro
      studies indicate that SRC-2 physically associates with ER and PR, very little is
      known about receptor-coactivator interactions in brain. Therefore, we used pull
      down assays to test the hypotheses that SRC-2 from hypothalamic and hippocampal
      tissue physically associate with ER and PR subtypes in a ligand-dependent manner.
      SRC-2 from both brain regions interacted with ER(alpha) bound to agonist, but not
      in the absence of ligand or in the presence of the selective ER modulator,
      tamoxifen. Analysis by mass spectrometry confirmed these ligand-dependent
      interactions between ER(alpha) and SRC-2 from brain. In dramatic contrast, SRC-2
      from brain showed little to no interaction with ERbeta. Interestingly, SRC-2 from
      both brain regions interacted with PR-B, but not PR-A, in a ligand-dependent
      manner. Taken together, these findings reveal that SRC-2 is expressed in brain
      regions known to mediate a variety of steroid-dependent functions. Furthermore,
      SRC-2 is expressed in many ER(alpha) containing cells in the hypothalamus.
      Finally, SRC-2 from brain interacts with ER and PR in a subtype-specific manner,
      which may contribute to the functional differences of these steroid receptor
      subtypes in brain.

PMID- 20678997
TI  - The patellar tendon bar! Is it a necessary feature?
AB  - The purpose of this investigation was to vary the load on the patellar tendon bar
      and to study the subsequent effect this has on the pattern of the pressure
      distribution at the stump-socket interface. Ten male subjects from the Southern
      General Hospital in Glasgow, UK participated in this study. Measuring systems
      utilising strain gauge and electrohydraulic technologies were designed, developed
      and constructed to enable pressure measurements to be conducted. One transducer,
      the patellar tendon (PT) transducer, was attached to the patellar tendon bar of
      the socket such that the patellar tendon bar was capable of being translated by
      +/-10 mm towards or away from the tendon. The results of this study showed that
      the position of the patellar tendon bar had no significant effect on the pressure
      distribution around the socket indicating that it is an unnecessary feature,
      which, we propose, may be eliminated during manufacture of a trans-tibial socket.

PMID- 20678998
TI  - An efficient technique for adjusting and maintaining specific hydration levels in
      soft biological tissues in vitro.
AB  - Elucidating how mechanics is affected by hydration in soft biological tissues is
      critical for understanding the potential effects of diseases where tissue
      extracellular matrix (ECM) is altered. The ability to control ECM water content
      is necessary for studying hydration-dependent tissue mechanics and for minimizing
      confounding effects caused by differences in tissue water content among
      specimens. In this paper, we describe an approach to adjust and maintain water
      content using a two-stage hydration technique, in order to overcome unique
      challenges faced in mechanical testing of biological tissues. Bovine aortic
      tissue was selected to demonstrate the approach. A liquid phase approach using
      PEG solutions allowed for efficient initial adjustment of tissue hydration. This
      was followed by a vapor phase approach using a humidity chamber for maintaining
      stable water content for a defined test duration of 45 min. Incubation in PEG
      solution brought bovine aortic tissue samples to equilibrium water content in
      approximately 6 h, much more efficiently than using a humidity chamber alone.
      Characteristic relationships between tissue water content and PEG concentration
      as well as relative humidity were obtained. It was found that PEG concentrations
      ranging from 0 to 40% had an inverse relationship with tissue water content
      ranging from 80 to 380%, which corresponded to relative humidities between 53 and
      99%.

PMID- 20678999
TI  - Albumin fusion of thioredoxin--the production and evaluation of its biological
      activity for potential therapeutic applications.
AB  - Thioredoxin-1 (Trx) is a redox-active protein with anti-inflammatory effects. The
      effect of albumin fusion on the pharmacokinetic and pharmacodynamic properties of
      Trx was evaluated in this study. The findings indicate that the properties of
      human serum albumin and the fusion protein are comparable. The fusion protein
      showed similar plasma concentration and organ distribution profiles as human
      serum albumin. The fusion protein accumulated in lungs, reaching levels higher
      than Trx. In an insulin reducing assay, the activity of the fusion protein was
      60% of the activity of Trx. However, survival rate of endotoxic shock mice
      induced by the administration of a lipopolysaccharide and D-galactosamine for
      fusion protein was double that of Trx. The findings reported herein indicate that
      the fusion protein is likely to have great clinical applications in areas such as
      the treatment of reperfusion injuries.

PMID- 20679001
TI  - Boundary conditions for simulating large SAW devices using ANSYS.
AB  - In this report, we propose improved substrate left and right boundary conditions
      for simulating SAW devices using ANSYS. Compared with the previous methods, the
      proposed method can greatly reduce computation time. Furthermore, the longer the
      distance from the first reflector to the last one, the more computation time can
      be reduced. To verify the proposed method, a design example is presented with
      device center frequency 971.14 MHz.

PMID- 20679000
TI  - Vitamin A supplementation to pregnant and breastfeeding female rats induces
      oxidative stress in the neonatal lung.
AB  - Vitamin A is an essential micronutrient that regulates many biological processes
      through modulation of retinoic acid receptor-responsive genes. Vitamin A acts as
      a systemic antioxidant, participating in the modulation of diverse redox
      mechanisms involved in physiological and pathological processes. Different
      studies, however, observed that vitamin A and other retinoids may induce pro
      oxidant/deleterious actions under certain conditions, leading to impairment of
      brain and lung function. Here, we studied the effect of vitamin A treatment at
      oral doses of 100 IU/kg, 200 IU/kg, and 300 IU/kg to female rats (Rattus
      norvegicus) during pregnancy and lactation on oxidative parameters of lungs from
      the offspring vitamin A supplementation induced increases in lipoperoxidation,
      protein carbonyl, activities of the antioxidant enzymes superoxide dismutase and
      catalase (200 IU/kg, and 300 IU/kg), and decreased sulphydryl protein (500 IU/kg)
      content in the neonatal lung.

PMID- 20679002
TI  - Nonlinear acoustics in higher-order approximation: Comment.
AB  - Some useful expressions for the second- and third-order equations for harmonic
      generation of infinite plane acoustic waves in a nonlinear non-viscous fluid are
      corrected. The concern addressed in the present comment is to point out some
      typographical errors in the first-order velocity and pressure expressions
      intervening in the calculation of the secondorder nonlinear equations, as well as
      a miscalculation of the axial component of the third-order Lighthill tensor term
      and the resulting third-order velocity and pressure equations presented in that
      paper.

PMID- 20679003
TI  - Thickness dependence of dielectric nonlinearity of lead zirconate titanate films.
AB  - The first-order reversal curves (FORC) distribution of PbZr(0.52)Ti(0.48)O3 thin
      films was characterized as a function of film thickness. It was found that the
      thickness dependence of the small-field dielectric constant is due primarily to
      differences in the domain wall contributions to the properties. The irreversible
      FORC distribution decreased and the switching fields increased as the thickness
      decreased; this is compatible with reported Rayleigh analyses. The polarization
      electric field data and the ac field dependence of the dielectric constant were
      modeled using the FORC distributions, and were found to give a good fit to the
      experimental results. Some discrepancies remain in the high-field dielectric
      constant, probably caused by its definition.

PMID- 20679004
TI  - 3-D in vitro estimation of temperature using the change in backscattered
      ultrasonic energy.
AB  - Temperature imaging with a non-invasive modality to monitor the heating of tumors
      during hyperthermia treatment is an attractive alternative to sparse invasive
      measurement. Previously, we predicted monotonic changes in backscattered energy
      (CBE) of ultrasound with temperature for certain sub-wavelength scatterers. We
      also measured CBE values similar to our predictions in bovine liver, turkey
      breast muscle, and pork rib muscle in 2-D in vitro studies and in nude mice
      during 2-D in vivo studies. To extend these studies to three dimensions, we
      compensated for motion and measured CBE in turkey breast muscle. 3-D data sets
      were assembled from images formed by a phased-array imager with a 7.5-MHz linear
      probe moved in 0.6-mm steps in elevation during uniform heating from 37 to 45
      degrees C in 0.5 degrees C increments. We used cross-correlation as a similarity
      measure in RF signals to automatically track feature displacement as a function
      of temperature. Feature displacement was non-rigid. Envelopes of image regions,
      compensated for non-rigid motion, were found with the Hilbert transform then
      smoothed with a 3 x 3 running average filter before forming the backscattered
      energy at each pixel. CBE in 3-D motion-compensated images was nearly linear with
      an average sensitivity of 0.30 dB/ degrees C. 3-D estimation of temperature in
      separate tissue regions had errors with a maximum standard deviation of about 0.5
      degrees C over 1-cm(3) volumes. Success of CBE temperature estimation based on 3
      D non-rigid tracking and compensation for real and apparent motion of image
      features could serve as the foundation for the eventual generation of 3-D
      temperature maps in soft tissue in a non-invasive, convenient, and low-cost way
      in clinical hyperthermia.

PMID- 20679005
TI  - Information tracking approach to segmentation of ultrasound imagery of the
      prostate.
AB  - The volume of the prostate is known to be a pivotal quantity used by clinicians
      to assess the condition of the gland during prostate cancer screening. As an
      alternative to palpation, an increasing number of methods for estimation of the
      volume of the prostate are based on using imagery data. The necessity to process
      large volumes of such data creates a need for automatic segmentation tools which
      would allow the estimation to be carried out with maximum accuracy and
      efficiency. In particular, the use of transrectal ultrasound (TRUS) imaging in
      prostate cancer screening seems to be becoming a standard clinical practice
      because of the high benefit-to-cost ratio of this imaging modality.
      Unfortunately, the segmentation of TRUS images is still hampered by relatively
      low contrast and reduced SNR of the images, thereby requiring the segmentation
      algorithms to incorporate prior knowledge about the geometry of the gland. In
      this paper, a novel approach to the problem of segmenting the TRUS images is
      described. The proposed approach is based on the concept of distribution
      tracking, which provides a unified framework for modeling and fusing image
      related and morphological features of the prostate. Moreover, the same framework
      allows the segmentation to be regularized by using a new type of weak shape
      priors, which minimally bias the estimation procedure, while rendering the
      procedure stable and robust. The value of the proposed methodology is
      demonstrated in a series of in silico and in vivo experiments.

PMID- 20679007
TI  - Optimal beamforming in ultrasound using the ideal observer.
AB  - Beamforming of received pulse-echo data generally involves the compression of
      signals from multiple channels within an aperture. This compression is
      irreversible, and therefore allows the possibility that information relevant for
      performing a diagnostic task is irretrievably lost. The purpose of this study was
      to evaluate information transfer in beamforming using a previously developed
      ideal observer model to quantify diagnostic information relevant to performing a
      task. We describe an elaborated statistical model of image formation for fixed
      focus transmission and single-channel reception within a moving aperture, and we
      use this model on a panel of tasks related to breast sonography to evaluate
      receive-beamforming approaches that optimize the transfer of information. Under
      the assumption that acquisition noise is well described as an additive wide-band
      Gaussian white-noise process, we show that signal compression across receive
      aperture channels after a 2-D matched-filtering operation results in no loss of
      diagnostic information. Across tasks, the matched-filter beamformer results in
      more information than standard delay-and-sum beamforming in the subsequent radio
      frequency signal by a factor of two. We also show that for this matched filter,
      68% of the information gain can be attributed to the phase of the matched-filter
      and 21% can be attributed to the amplitude. A 1-D matched filtering along axial
      lines shows no advantage over delay-andsum, suggesting an important role for
      incorporating correlations across different aperture windows in beamforming. We
      also show that a post-compression processing before the computation of an
      envelope is necessary to pass the diagnostic information in the beamformed radio
      frequency signal to the final envelope image.

PMID- 20679006
TI  - High-resolution, high-contrast ultrasound imaging using a prototype dual
      frequency transducer: in vitro and in vivo studies.
AB  - With recent advances in animal models of disease, there has been great interest
      in capabilities for highresolution contrast-enhanced ultrasound imaging.
      Microbubble contrast agents are unique in that they scatter broadband ultrasound
      energy because of their nonlinear behavior. For optimal response, it is desirable
      to excite the microbubbles near their resonant frequency. To date, this has been
      challenging with high-frequency imaging systems because most contrast agents are
      resonant at frequencies in the order of several megahertz. Our team has developed
      a unique dual-frequency confocal transducer which enables low-frequency
      excitation of bubbles near their resonance with one element, and detection of
      their emitted high-frequency content with the second element. Using this imaging
      approach, we have attained an average 12.3 dB improvement in contrast-to-tissue
      ratios over fundamental mode imaging, with spatial resolution near that of the
      high-frequency element. Because this detection method does not rely on signal
      decorrelation, it is not susceptible to corruption by tissue motion. This probe
      demonstrates contrast imaging capability with significant tissue suppression,
      enabling high-resolution contrast-enhanced images of microvascular blood flow.
      Additionally, this probe can readily produce radiation force on flowing contrast
      agents, which may be beneficial for targeted imaging or therapy.

PMID- 20679008
TI  - Ultrasonic waveguide with square wave surface grating.
AB  - The effect of spatial harmonics of a square-wave surface grating on the multiband
      frequency response of ultrasonic SH waves in an elastic plate is investigated.
      Stopbands are found to occur under simultaneous occurrence of first-order and
      higher-order Bragg resonances together with co-directional and/or contra
      directional mode coupling conditions. The odd harmonic nature of the structure
      causes stopbands to appear above the cutoff frequencies of the odd-numbered
      modes. The attenuation within stopbands is found to be greatest when all
      propagating modes are coupled and reflected. The simultaneous resonance
      conditions for higher order stopbands must contain at least one co-directional
      mode coupling condition. The analysis is performed according to the multiple
      scales scheme, leading to the derivation of coupled mode equations, which are
      solved numerically using the fundamental matrix method.

PMID- 20679009
TI  - Acoustic velocities of shear waves in La3Ga(5.5)Ta(0.5)O14 piezoelectric crystal
      using singular value decomposition.
AB  - La3Ga(5.5)Ta(0.5)O14 (LGT) is a new piezoelectric material with superior
      electromechanical properties and high Q.f product. Transverse-wave splitting
      behavior of LGT was observed in the acoustic velocity measurements. The
      velocities of the two shear waves propagating in Y-(010) direction are very close
      and they cannot be separated completely. This has a tremendous influence on
      determining the correct velocity of the shear modes. It is proposed that the
      singular value decomposition (SVD) technique can be used to determine the
      splitting time of two shear modes in Y-plane LGT crystal. Moreover, it also helps
      to correct the arrival time of the transverse waves. It is believed that the
      presented approach is efficient and accurate for determining the correct
      velocities of shear modes in anisotropic media.

PMID- 20679010
TI  - AlN/ZnO/diamond waveguiding layer acoustic wave structure: theoretical and
      experimental results.
AB  - We present a theoretical calculation and experimental results for a waveguiding
      layer acoustic wave (WLAW). The experimental device is modeled by the finite
      element method (FEM) for the AlN/ZnO/diamond structure. It was found that the AlN
      thickness must be at least larger than 3lambda/2 to obtain negligible surface
      displacement. In the same way, the ZnO thickness for a fixed value of AlN
      thickness at 2lambda must be larger than lambda/4 to confine the acoustic wave.
      The electromechanical coupling of the wave presents an optimum around lambda/2
      for the ZnO layer thickness. A first experimental AlN/ZnO/diamond device has been
      developed and shows the WLAW at 412 MHz.

PMID- 20679011
TI  - Rotary-linear piezoelectric microactuator with a cubic stator of side length 3.5
      mm.
AB  - We report a miniature rotary-linear piezoelectric actuator with a single cubic
      stator of side length 3.5 mm which can generate rotary motion around the center
      axis and linear motion in the axial direction. The stator is fabricated as a
      single metallic cube of side length 3.5 mm with a 2.5-mm diameter through-hole
      and four piezoelectric elements bonded to the sides of the stator. The simplicity
      makes the actuator compact without any special manufacturing. In the design for
      miniaturization, the modal analysis using the finite element method indicates the
      natural frequency of the stator from the side length 14 mm to 3.5 mm. In the
      experiments, rotary motion of 24 rad/s and 2.5 microNm were obtained at a
      resonant frequency of 280 kHz, and linear motion of 80 mm/s and 2.6 mN was
      observed at 305 kHz by driving the system at an applied voltage of 42 V(rms).

PMID- 20679012
TI  - Theory and experimental verifications of the resonator Q and equivalent
      electrical parameters due to viscoelastic and mounting supports losses.
AB  - A novel analytical/numerical method for calculating the resonator Q and its
      equivalent electrical parameters due to viscoelastic, conductivity, and mounting
      supports losses is presented. The method presented will be quite useful for
      designing new resonators and reducing the time and costs of prototyping. There
      was also a necessity for better and more realistic modeling of the resonators
      because of miniaturization and the rapid advances in the frequency ranges of
      telecommunication. We present new 3-D finite elements models of quartz resonators
      with viscoelasticity, conductivity, and mounting support losses. The losses at
      the mounting supports were modeled by perfectly matched layers (PMLs). A
      previously published theory for dissipative anisotropic piezoelectric solids was
      formulated in a weak form for finite element (FE) applications. PMLs were placed
      at the base of the mounting supports to simulate the energy losses to a semi
      infinite base substrate. FE simulations were carried out for free vibrations and
      forced vibrations of quartz tuning fork and AT-cut resonators. Results for quartz
      tuning fork and thickness shear AT-cut resonators were presented and compared
      with experimental data. Results for the resonator Q and the equivalent electrical
      parameters were compared with their measured values. Good equivalences were
      found. Results for both low- and high-Q AT-cut quartz resonators compared well
      with their experimental values. A method for estimating the Q directly from the
      frequency spectrum obtained for free vibrations was also presented. An important
      determinant of the quality factor Q of a quartz resonator is the loss of energy
      from the electrode area to the base via the mountings. The acoustical
      characteristics of the plate resonator are changed when the plate is mounted onto
      a base substrate. The base affects the frequency spectra of the plate resonator.
      A resonator with a high Q may not have a similarly high Q when mounted on a base.
      Hence, the base is an energy sink and the Q will be affected by the shape and
      size of this base. A lower-bound Q will be obtained if the base is a semi
      infinite base because it will absorb all acoustical energies radiated from the
      resonator.

PMID- 20679013
TI  - Analytical study of dual-mode thin film bulk acoustic resonators (FBARs) based on
      ZnO and AlN films with tilted c-axis orientation.
AB  - In this paper, we present the analytical study of thin film bulk acoustic wave
      resonators (FBARs) using ZnO and AlN films with a c-axis tilt angle (off-normal)
      from 0 degrees to 180 degrees. The tilted c-axis orientation induces normal plane
      and inplane polarizations, which leads to the coexistence of the longitudinal
      mode and shear mode in the resonator. The equation for predicting electric
      impedance of FBARs was derived from the basic piezoelectric constitutive
      equations. Material properties including elastic, dielectric, and piezoelectric
      coefficients, bulk wave properties including acoustic velocity and
      electromechanical coupling coefficient, and impedance of FBARs were calculated
      and showed strong dependence on the tilt angle. Interestingly, it was found that
      for ZnO FBARs, pure thickness longitudinal modes occur at 0 degrees and 65.4
      degrees, and pure thickness shear modes occur at 43 degrees and 90 degrees. For
      AlN FBARs, pure longitudinal modes occur at 0 degrees and 67.1 degrees, and pure
      shear modes occur at 46.1 degrees and 90 degrees for AlN. In other words, pure
      thickness longitudinal and shear modes exist in ZnO and AlN FBARs at specific
      tilted polarization angles. In addition, two peaks of shear mode
      electromechanical coefficient are found at 33.3 degrees and 90 degrees for ZnO,
      and 34.5 degrees and 90 degrees for AlN. Therefore, ZnO and AlN films with
      specific tilt angles may provide options in the design and fabrication of FBARs,
      considering their strong shear resonance with high electromechanical
      coefficients. The use of dual-mode FBARs for mass sensors is also analyzed; the
      calculated large resonant frequency shift caused by mass loading shows that they
      have good prospects for use in sensor applications with high sensitivity. The
      simulation results agreed well with the reported experiment results, and can be
      used for design and application of FBARs.

PMID- 20679014
TI  - Considerations for measurement setup for second-order nonlinearity in radio
      frequency bulk acoustic wave duplexers.
AB  - This paper discusses the influence of the setup on the measurement reliability
      and reproducibility for the secondorder inter-modulation distortion (IMD2)
      generated in RF BAW duplexers. Our measurement results show that the IMD2 level
      can be reliably and reproducibly measured when the port terminations are properly
      applied. For example, a filter and a relatively large (>20 dB) attenuator are
      necessary between an oscillator and the antenna port of the duplexer to suppress
      the nonlinear mixing and the impedance mismatching. If the order of these two
      devices were reversed, the IMD2 level would change significantly. Although an
      isolator is commonly used to stabilize the power amplifier output, our research
      results show that not using an ISO produced more accurate results.

PMID- 20679015
TI  - A high-power linear ultrasonic motor using longitudinal vibration transducers
      with single foot.
AB  - A high-power linear ultrasonic motor using longitudinal vibration transducers
      with single foot was proposed in this paper. The stator of proposed motor
      contains a horizontal transducer and a vertical transducer. Longitudinal
      vibrations are superimposed in the stator and generate an elliptical trajectory
      at the driving foot. The sensitivity analysis of structural parameters to the
      resonance frequencies of two working modes of the stator was performed using the
      finite element method. The resonance frequencies of two working modes were
      degenerated by adjusting the structural parameters. The vibration characteristics
      of stator were studied and discussed. A prototype motor was fabricated and
      measured. Typical output of the prototype is a no-load speed of 1160 mm/s and
      maximum thrust force of 20 N at a voltage of 200 V(rms).

PMID- 20679016
TI  - A piezoelectric ultrasonic linear micromotor using a slotted stator.
AB  - A novel ultrasonic micro linear motor that uses 1st longitudinal and 2nd bending
      modes, derived from a bartype stator with a rectangular slot cut through the
      stator length, has been proposed and designed for end-effect devices of
      microrobotics and bio-medical applications. The slot structure plays an important
      role in the motor design, and can be used not only to tune the resonance
      frequency of the two vibration modes but also to reduce the undesirable
      longitudinal coupling displacement caused by bending vibration at the end of the
      stator. By using finite element analysis, the optimal slot dimension to improve
      the driving tip motion was determined, resulting in the improvement of the motor
      performance. The trial linear motor, with a weight of 1.6 g, gave a maximum
      driving velocity of 1.12 m/s and a maximum driving force of 3.4 N. A maximum
      mechanical output power of 1.1 W was obtained at force of 1.63 N and velocity of
      0.68 m/s. The output mechanical power per unit weight was 688 W/kg.

PMID- 20679017
TI  - Propagation of shear horizontal surface waves in a layered piezoelectric half
      space with an imperfect interface.
AB  - We investigate the dispersive behavior of shear horizontal (SH) surface waves
      propagating in a layered structure consisting of a piezoelectric layer and an
      elastic half-space, in which the top and bottom of the layer are electrically
      shorted. The interface between the layer and the half-space is assumed to be
      imperfect bonding. The degree of imperfection of the interface is described by
      the so-called shear-lag model. The dispersion equations are expressed in an
      explicit closed form. The phase velocities are calculated to show the influences
      of the interfacial imperfection and the material properties of piezoelectric
      layers on the dispersive characteristics.

PMID- 20679018
TI  - Stress-induced frequency shifts of degenerate thickness-shear modes in rotated Y
      cut quartz resonators.
AB  - We study stress-induced frequency shifts in a rotated Y-cut quartz resonator
      (theta = 23.7 degrees ) with degenerate fundamental thickness-shear modes when
      the biasing stress is not present. Using the recently derived perturbation
      procedure for degenerate frequencies in crystal resonators, we show that when a
      planar stress system is applied, the degenerate frequency splits into two. This
      phenomenon is expected to be typical for degenerate frequencies in crystal
      resonators and may be responsible in part for the jump discontinuities in
      frequency temperature curves and other frequency jump phenomena.

PMID- 20679019
TI  - A fast algorithm for adaptive clutter rejection in ultrasound color flow imaging
      based on the first-order perturbation: a simulation study.
AB  - A fast clutter rejection method for ultrasound color flow imaging is proposed
      based on the first-order perturbation as an efficient implementation of eigen
      decomposition. The proposed method is verified by simulated data. Results show
      that the proposed method can be adaptive to non-stationary clutter movements and
      its computational complexity is lower than that of the conventional eigen-based
      clutter rejection methods.

PMID- 20679020
TI  - Application of a real-time, calculable limiting form of the Renyi entropy for
      molecular imaging of tumors.
AB  - Previously, we reported new methods for ultrasound signal characterization using
      entropy, H(f); a generalized entropy, the Renyi entropy, I(f)(r); and a limiting
      form of Renyi entropy suitable for real-time calculation, I(f),(infinity). All of
      these quantities demonstrated significantly more sensitivity to subtle changes in
      scattering architecture than energy-based methods in certain settings. In this
      study, the real-time calculable limit of the Renyi entropy, I(f),(infinity), is
      applied for the imaging of angiogenic murine neovasculature in a breast cancer
      xenograft using a targeted contrast agent. It is shown that this approach may be
      used to reliably detect the accumulation of targeted nanoparticles at five
      minutes post-injection in this in vivo model.

PMID- 20679021
TI  - Thickness or phase velocity measurements using the Green's function comparison
      method.
AB  - The acoustic guided wave propagation for plate thickness measurement is generally
      treated in free space to simplify the formal approach. In this paper, propagation
      in a closed environment is treated by dealing with plates of finite dimensions
      and arbitrary geometries and linear boundary conditions. The present approach
      considers the plate Green's function to be composed of two terms. The first term
      corresponds to the Green's function of an infinite plate. The second term
      corresponds to a correction term which, in addition to the first term, satisfies
      all equations. Assuming the boundary conditions to be linear, it is found that
      the acoustic wave generated by a point source is proportional to that of a
      circular array of sources centered on it. By measuring the ratio between the two
      signals, either the plate velocity or plate thickness can be determined. This new
      method has been successfully applied to isotropic and anisotropic homogeneous
      plates of different geometries, on inhomogeneous plates, and also in a passive
      mode, without an active transmitter.

PMID- 20679022
TI  - Automatic and unsupervised snore sound extraction from respiratory sound signals.
AB  - In this paper, an automatic and unsupervised snore detection algorithm is
      proposed. The respiratory sound signals of 30 patients with different levels of
      airway obstruction were recorded by two microphones: one placed over the trachea
      (the tracheal microphone), and the other was a freestanding microphone (the
      ambient microphone). All the recordings were done simultaneously with full-night
      polysomnography during sleep. The sound activity episodes were identified using
      the vertical box (V-Box) algorithm. The 500-Hz subband energy distribution and
      principal component analysis were used to extract discriminative features from
      sound episodes. An unsupervised fuzzy C-means clustering algorithm was then
      deployed to label the sound episodes as either snore or no-snore class, which
      could be breath sound, swallowing sound, or any other noise. The algorithm was
      evaluated using manual annotation of the sound signals. The overall accuracy of
      the proposed algorithm was found to be 98.6% for tracheal sounds recordings, and
      93.1% for the sounds recorded by the ambient microphone.

PMID- 20679023
TI  - CFD modeling of an ultrasonic separator for the removal of lipid particles from
      pericardial suction blood.
AB  - A computational fluid dynamics (CFD) model is presented to simulate the removal
      of lipid particles from blood using a novel ultrasonic quarter-wavelength
      separator. The Lagrangian-Eulerian CFD model accounts for conservation of mass
      and momentum, for the presence of lipid particles of a range of diameters, for
      the acoustic force as experienced by the particles in the blood, as well as for
      gravity and other particle-fluid interaction forces. In the separator, the liquid
      flows radially inward within a fluid chamber formed between a disc-shaped
      transducer and a disc-shaped reflector. Following separation of the lipid
      particles, blood exits the separator axially through a central opening on the
      disc-shaped reflector. Separator diameters studied varied between 12 and 18 cm,
      and gap sizes between the discs of 600 MUm, 800 MUm and 1 mm were considered.
      Results show a strong effect of residence time of the particles within the
      chamber on the separation performance. Different separator configurations were
      identified, which could give a lipid removal performance of 95% or higher when
      processing 62.5 cm (3)/min of blood. The developed model provides a design method
      for the selection of geometric and operating parameters for the ultrasonic
      separator.

PMID- 20679025
TI  - Multiple functional ECG signal is processing for wearable applications of long
      term cardiac monitoring.
AB  - In this paper, an integrated electrocardiogram (ECG) signal-processing scheme is
      proposed. Using a systematic wavelet transform algorithm, this signal-processing
      scheme can realize multiple functions in real time, including baseline-drift
      removal, noise suppression, QRS detection, heart beat rate prediction and
      classification, and clean ECG reconstruction. Utilizing the novel low-cost
      hardware architecture, the proposed ECG signal-processing scheme is implemented
      in application-specific integrated circuits with 0.18 MU m CMOS technology. This
      ECG signal-processor chip achieves low area and power consumptions, and is highly
      suitable for wearable applications of long-term cardiac monitoring.

PMID- 20679026
TI  - A computer assisted method for nuclear cataract grading from slit-lamp images
      using ranking.
AB  - In clinical diagnosis, a grade indicating the severity of nuclear cataract is
      often manually assigned by a trained ophthalmologist to a patient after comparing
      the lens' opacity severity in his/her slit-lamp images with a set of standard
      photos. This grading scheme is often subjective and time-consuming. In this
      paper, a novel computer-aided diagnosis method via ranking is proposed to
      facilitate nuclear cataract grading following conventional clinical decision
      making process. The grade of nuclear cataract in a slit-lamp image is predicted
      using its neighboring labeled images in a ranked image list, which is achieved
      using a learned ranking function. This ranking function is learned via direct
      optimization on a newly proposed approximation to a ranking evaluation measure.
      Our proposed method has been evaluated by a large dataset composed of 1000
      different cases, which are collected from an ongoing clinical population-based
      study. Both experimental results and comparison with several existing methods
      demonstrate the benefit of grading via ranking by our proposed method.

PMID- 20679027
TI  - Uniform motion blur in Poissonian noise: blur/noise tradeoff.
AB  - In this paper we consider the restoration of images corrupted by both uniform
      motion blur and Poissonian noise. We formulate an image formation model that
      explicitly takes into account the length of the blur point-spread function and
      the noise level as functions of the exposure time. Further, we present an
      analysis of the achievable restoration performance by showing how the root mean
      squared error varies with respect to the exposure time. It turns out that the
      worst situations are represented by either too short or too long exposure times.
      In between there exists an optimal exposure time that maximizes the restoration
      performance, balancing the amount of blur and noise in the observation. We
      justify such result through a mathematical analysis of the signal-to-noise ratio
      in Fourier domain; this study is then validated by deblurring synthetic data as
      well as camera raw data.

PMID- 20679028
TI  - Combined invariants to similarity transformation and to blur using orthogonal
      Zernike moments.
AB  - The derivation of moment invariants has been extensively investigated in the past
      decades. In this paper, we construct a set of invariants derived from Zernike
      moments which is simultaneously invariant to similarity transformation and to
      convolution with circularly symmetric point spread function (PSF). Two main
      contributions are provided: the theoretical framework for deriving the Zernike
      moments of a blurred image and the way to construct the combined geometric-blur
      invariants. The performance of the proposed descriptors is evaluated with various
      PSFs and similarity transformations. The comparison of the proposed method with
      the existing ones is also provided in terms of pattern recognition accuracy,
      template matching and robustness to noise. Experimental results show that the
      proposed descriptors perform on the overall better.

PMID- 20679029
TI  - Fast sparse image reconstruction using adaptive nonlinear filtering.
AB  - Compressed sensing is a new paradigm for signal recovery and sampling. It states
      that a relatively small number of linear measurements of a sparse signal can
      contain most of its salient information and that the signal can be exactly
      reconstructed from these highly incomplete observations. The major challenge in
      practical applications of compressed sensing consists in providing efficient,
      stable and fast recovery algorithms which, in a few seconds, evaluate a good
      approximation of a compressible image from highly incomplete and noisy samples.
      In this paper, we propose to approach the compressed sensing image recovery
      problem using adaptive nonlinear filtering strategies in an iterative framework,
      and we prove the convergence of the resulting two-steps iterative scheme. The
      results of several numerical experiments confirm that the corresponding algorithm
      possesses the required properties of efficiency, stability and low computational
      cost and that its performance is competitive with those of the state of the art
      algorithms.

PMID- 20679030
TI  - Geometric calibration of lens and filter distortions for multispectral filter
      wheel cameras.
AB  - High-fidelity color image acquisition with a multispectral camera utilizes
      optical filters to separate the visible electromagnetic spectrum into several
      passbands. This is often realized with a computer-controlled filter wheel, where
      each position is equipped with an optical bandpass filter. For each filter wheel
      position, a grayscale image is acquired and the passbands are finally combined to
      a multispectral image. However, the different optical properties and non-coplanar
      alignment of the filters cause image aberrations since the optical path is
      slightly different for each filter wheel position. As in a normal camera system,
      the lens causes additional wavelength-dependent image distortions called
      chromatic aberrations. When transforming the multispectral image with these
      aberrations into an RGB image, color fringes appear, and the image exhibits a
      pincushion or barrel distortion. In this paper, we address both the distortions
      caused by the lens and by the filters. Based on a physical model of the bandpass
      filters, we show that the aberrations caused by the filters can be modeled by
      displaced image planes. The lens distortions are modeled by an extended pinhole
      camera model, which results in a remaining mean calibration error of only 0.07
      pixels. Using an absolute calibration target, we then geometrically calibrate
      each passband and compensate for both lens and filter distortions simultaneously.
      We show that both types of aberrations can be compensated and present detailed
      results on the remaining calibration errors.

PMID- 20679031
TI  - 3-D target-based distributed smart camera network localization.
AB  - For distributed smart camera networks to perform vision-based tasks such as
      subject recognition and tracking, every camera's position and orientation
      relative to a single 3-D coordinate frame must be accurately determined. In this
      paper, we present a new camera network localization solution that requires
      successively showing a 3-D feature point-rich target to all cameras, then using
      the known geometry of a 3-D target, cameras estimate and decompose projection
      matrices to compute their position and orientation relative to the
      coordinatization of the 3-D target's feature points. As each 3-D target position
      establishes a distinct coordinate frame, cameras that view more than one 3-D
      target position compute translations and rotations relating different positions'
      coordinate frames and share the transform data with neighbors to facilitate
      realignment of all cameras to a single coordinate frame. Compared to other
      localization solutions that use opportunistically found visual data, our solution
      is more suitable to battery-powered, processing-constrained camera networks
      because it requires communication only to determine simultaneous target viewings
      and for passing transform data. Additionally, our solution requires only pairwise
      view overlaps of sufficient size to see the 3-D target and detect its feature
      points, while also giving camera positions in meaningful units. We evaluate our
      algorithm in both real and simulated smart camera networks. In the real network,
      position error is less than 1 ('') when the 3-D target's feature points fill only
      2.9% of the frame area.

PMID- 20679032
TI  - A new hybrid method for image approximation using the easy path wavelet
      transform.
AB  - The easy path wavelet transform (EPWT) has recently been proposed by one of the
      authors as a tool for sparse representations of bivariate functions from discrete
      data, in particular from image data. The EPWT is a locally adaptive wavelet
      transform. It works along pathways through the array of function values and
      exploits the local correlations of the given data in a simple appropriate manner.
      However, the EPWT suffers from its adaptivity costs that arise from the storage
      of path vectors. In this paper, we propose a new hybrid method for image
      approximation that exploits the advantages of the usual tensor product wavelet
      transform for the representation of smooth images and uses the EPWT for an
      efficient representation of edges and texture. Numerical results show the
      efficiency of this procedure.

PMID- 20679033
TI  - Adaptive sequential prediction of multidimensional signals with applications to
      lossless image coding.
AB  - We investigate the problem of designing adaptive sequential linear predictors for
      the class of piecewise autoregressive multidimensional signals, and adopt an
      approach of minimum description length (MDL) to determine the order of the
      predictor and the support on which the predictor operates. The design objective
      is to strike a balance between the bias and variance of the prediction errors in
      the MDL criterion. The predictor design problem is particularly interesting and
      challenging for multidimensional signals (e.g., images and videos) because of the
      increased degree of freedom in choosing the predictor support. Our main result is
      a new technique of sequentializing a multidimensional signal into a sequence of
      nested contexts of increasing order to facilitate the MDL search for the order
      and the support shape of the predictor, and the sequentialization is made
      adaptive on a sample by sample basis. The proposed MDL-based adaptive predictor
      is applied to lossless image coding, and its performance is empirically
      established to be the best among all the results that have been published till
      present.

PMID- 20679034
TI  - Studentized dynamical system for robust object tracking.
AB  - This paper describes a studentized dynamical system (SDS) for robust target
      tracking using a subspace representation. Dynamical systems (DS) provide a
      powerful framework for the probabilistic modeling of temporal sequences. Visual
      tracking problems are often cast as a sequential inference problem within the DS
      framework and a compact way to model the observation distributions (i.e., object
      appearances) is through probabilistic principal component analysis (PPCA). PPCA
      is a classic Gaussian based subspace representation method and a popular tool for
      appearance modeling. Although Gaussian density has theoretically nice properties,
      resulting in models that are always tractable, they are also severely limited in
      practical settings. One of the central issues in the use of PPCA for target
      appearance modeling is that it is very sensitive to outliers. The Gaussian
      density has a very light tail, while real world data with outliers exhibit heavy
      tails. Recently, more heavy-tailed distributions (e.g., Student's t-distribution)
      have been introduced to increase the robustness of the original PPCA. We propose
      to augment the traditional target tracking DS by adding a set of auxiliary latent
      variables to adjust the shape of the observation distribution. We show that by
      carefully choosing the probability density of these auxiliary latent variables, a
      more robust observation distribution can be obtained with tails heavier than
      Gaussian. Numerical experiments verify that the proposed SDS has a better
      capability to handle considerable amount of outlier noise and an improved
      tracking performance over DS with a Gaussian based observation model.

PMID- 20679035
TI  - [DNA microarrays and prediction of clinical outcome in ovarian carcinoma
      patients].
AB  - Despite debulking surgery and taxane/platinum-based chemotherapy, ovarian cancer
      is the most lethal pelvic gynaecological cancer in western countries, with a 25%
      5-years survival. Current histo-clinical prognostic factors are insufficient to
      capture the heterogeneous clinical outcome of patients. A better molecular
      characterization of the disease is crucial to refine the prognostic
      classifications and to identify new therapeutic targets. DNA microarrays, which
      allow the quantitative measurement of expression level of the whole genome
      simultaneously in a single tumor sample, have been recently used towards this
      objective with promising results. Here, we present and discuss the main published
      studies and the issues to address in the future to allow the expected transfer to
      clinical practice.

PMID- 20679036
TI  - [Homozygous sickle cell disease in Ivory Coast adults].
AB  - Sickle cell disease is a genetic disease characterized by the synthesis of an
      abnormal haemoglobin called haemoglobin S. It is the most frequent of the
      hereditary anomalies of haemoglobin and occurs most commonly in individuals of
      African descent. Various treatments have considerably improved its prognosis,
      prolonging the survival of patients, especially those with the most severe,
      homozygous form. The objective of thisstudy is to describe the epidemiologic,
      clinical, and laboratory characteristics as well as the disease course and
      available treatments in adults (aged 21 years or older). This retrospective,
      descriptive, analytic and non-comparative study included 48 adults of both sexes
      with homozygous sickle cell disease. Their mean age was 26.1 years (range: 21 to
      56 years, and sex ratio 1.3. In all, 70.8% had clinical anaemia, 83.3% were
      subicteric or icteric and 8.3% had hepatomegaly. Spleen size was normal in 41.7%
      of patients, and atrophic in 37.5%. No case of splenomegaly was noted and 8.3%
      had been splenectomised. Haemoglobin rates ranged from 4 g/dL to 12.7 g/dL with
      an average of 9.5 g/dL, haemoglobin S levels from 83 to 93% with an average of
      85.3%, and haemoglobin F levels from 3.5 to 17% with an average of 10.6%. The
      percentage with fewer than three crises (vasooclusive or haemolytic or both) in a
      year was 68.7%; 27.1% had from three to five crises, and 4.2% more than five.
      Disease complications included anaemia in 43.7%, infections in 18.8% and
      ischaemia in 16.7%; 20.8% had no complications. Age at the beginning of treatment
      was younger than 5 years in 56.25%, from 5 to 10 years in 29.2%, and older than
      10 years in 14.6%. Medical follow-up was regular for 68.7% and irregular for
      31.2%. Vaccination was up to date in 58.3. Most patients (83.3%) adhered to their
      maintenance treatment. In all, 41.7% had not had any blood transfusions, 54.2%
      had had one or two transfusions, and 4.2% three or more. We compared the patients
      aged 26 years or younger with those older than 26 and studied the influence of
      age on different disease variables. Age did not affect the frequency of crises (p
      = 0.368) or of infections (p = 0.116), the rates of haemoglobin (p = 0.221),
      haemoglobin S (p = 0.44), or haemoglobin F (p = 0.35), or complications (p =
      0.56). Nevertheless, we noted that the frequency of crises, infections, and
      anaemic complications were higher among the younger patients. Early treatment,
      regular medical follow-up, maintenance treatment and vaccination have all
      improved the prognosis of homozygous sickle cell disease considerably. These
      patients have reached adulthood with relatively few chronic complications.

PMID- 20679037
TI  - From trauma to acute care surgery: with an eye to the future.

PMID- 20679038
TI  - The triad of trauma, emergency surgery, and surgical critical care: practice
      patterns and financial considerations.

PMID- 20679039
TI  - Acute care surgery in the safety net hospital: maintaining referrals and
      optimizing outcomes.

PMID- 20679040
TI  - Gastroduodenal perforation: maximal or minimal intervention?

PMID- 20679041
TI  - Small bowel obstruction: the eternal dilemma of when to intervene.

PMID- 20679042
TI  - Cholecystectomy for acute gallstone pancreatitis: early vs delayed approach.

PMID- 20679043
TI  - Diverticulitis: the most common colon emergency for the acute care surgeon.

PMID- 20679044
TI  - Clostridium difficile colitis: a call for aggressive management.

PMID- 20679045
TI  - Twists and turns: a practical approach to volvulus and intussusception.

PMID- 20679046
TI  - Lower gastrointestinal bleeding of unknown origin: tricks of the trade.

PMID- 20679047
TI  - Mesenteric ischemia: the whole spectrum.

PMID- 20679048
TI  - [Shuttle test in severe COPD patients].
AB  - The shuttle test (ST) is a maximal exercise field test with scarcely used in
      Argentina. Our objective was to compare different variables of exercise response
      to ST vs. other exercise tests such as six minute walking test (SMWT) and
      cardiopulmonary with maximal oxygen consumption (VO2max) in severe COPD patients.
      A total of 21 stable severe COPD patients (GOLD III and IV stages) were evaluated
      with SMWT, ST and VO2max test. In all patients spirometry was performed with
      bronchodilator response, arterial gas and chronic respiratory questionnaire to
      evaluate quality of life. Cardiac frequency, oxygen saturation and dyspnea scale
      by Borg in response to exercise tests were evaluated. Paired T Student and
      Pearson tests were used, defining p < 0.05 as significant. COPD patients were
      65.27 +/- 12.72 years old and had severe airflow obstruction (FEV1: 33.23 +/-
      4.94%). The exercise response to SMWT was 297.85 +/- 173.24 meters; ST: 318.8 +/-
      42.42 meters and VO2max test: 14.7 +/- 5.44 ml/kg/min. The correlation between
      SMWT and ST was: r: 0.52(p < 0.00085); between ST and VO2max (l/min): r: 0.78 (p
      < 0.00079), and ST and VO2max (ml/kg/min): r: 0.81 (p < 0.00065). Moderate
      correlation was observed in final heart rate (r: 0.41, p < 0.00091), maximal Borg
      dyspnea scale (r: 0.47, p < 0.00099) and high correlation with final oxygen
      saturation (r: 0.81, p < 0.00087) between ST and VO2max. There was no correlation
      between ST and FEV1 and ST and quality of life. OUR CONCLUSION: The ST is a
      maximal, simple and low cost test. It has high correlation with cardiopulmonary
      test with VO2max measurement. It is a useful tool in those laboratories for
      pulmonary evaluations without possible availability of expensive tests.

PMID- 20679049
TI  - [Nodular hepatic lesions secondary to multiple myeloma].
AB  - Multiple myeloma is characterized by the neoplastic proliferation of a single
      clone of plasma cells producing a monoclonal immunoglobulin. Myelomatous nodular
      lesions of the liver are infrequent. We describe 3 cases with histological
      confirmation and we review the bibliography.

PMID- 20679050
TI  - [Clinical finding and follow-up of chronic constrictive pericarditis].
AB  - The aim of this study was to describe the etiology, clinical findings, diagnostic
      methods, treatment, outcome and long-term prognosis of 35 patients with chronic
      constrictive pericarditis (CCP) that were prospectively analyzed according to a
      pericardial disease protocol performed in our Institution. Etiology of CCP was
      idiopathic in 24 patients (68%), and specific in 11 (32%). The majority (34
      patients, 97%) underwent pericardiectomy. Perioperative mortality was 12% (4/33)
      no deaths were registered among patients with idiopathic CCP. Median follow-up
      was 5.6 years (percentile 25-75: 2.4-7.4 years). The cumulative actuarial
      survival probability was 97% at 1 year (confidence interval [CI] 80% to 99%); 83%
      at 5 years, (95% CI 65% to 93%); 78% at 7 years, (95% CI 60% to 90%), and 69% at
      10 years (95% CI 50% to 84%). In conclusion, nowadays CCP is generally an
      idiopathic disease with late diagnosis. The clinical course of the disease
      produces severe symptoms of congestive heart failure. In a 10 years follow-up 2/3
      of patients are alive and improved their quality of life. Idiopathic form of
      pericarditis did not show mortality during early postoperative period.

PMID- 20679051
TI  - Gender and perception of dyspnea. The role of the variation in the forced
      expiratory volume in one second.
AB  - During bronchoconstriction women perceive more breathlessness than men. The aims
      of study were 1) to evaluate if quality of dyspnea in bronchoconstriction was
      different in women and men 2) to assess if gender difference in the perception of
      dyspnea could be related to the level of bronchoconstriction. 457 subjects (257
      women) inhaled methacholine to a 20% decrease in FEV1, or 32 mg/ml. Dyspnea was
      evaluated using the modified Borg scale and a list of expressions of dyspnea.
      Borg scores were recorded immediately before the challenge test baseline and at
      the maximum FEV1 decrease. The prevalence of descriptors of dyspnea reported by
      women and men was similar. Dyspnea was related to the level of FEV1 (FEV1: OR
      1.05, 95%CI 1.01-1.09, p 0.0095), females (OR 2.90, 95%CI 1.33-6.33, p 0.0072),
      younger subjects (OR 0.93, 95%CI 0.89-0.97, p 0.0013) and body mass index (BMI)
      (OR 1.11, 95%CI 1.01-1.23, p 0.023). As the FEV1 fell less than 20% from
      baseline, only the FEV1 was significantly associated with dyspnea (FEV1:OR 1.15,
      95%CI 1.07-1.24, p 0.0002). Instead, if the FEV1 fell higher > or = 20%, the
      presence of dyspnea was related to the degree of bronchoconstriction (FEV1: OR
      1.04, 95%CI 1.01-1.09, p 0.0187), females (OR 3.02, 95%CI 1.36-6.72, p 0.0067),
      younger subjects (OR 0.92, 95%CI 0.88-0.96, p 0.0007) and BMI (OR 1.12, 95%CI
      1.01-1.23, p 0.023). The quality of dyspnea during the bronchoconstriction was
      similar in women and men; women showed a higher perception of dyspnea than men
      only when the FEV1 fell more than 20% from baseline.

PMID- 20679052
TI  - [Therapeutic management in 154 acromegalic patients].
AB  - Acromegaly is a chronic, invalidating disease due in over 95% of cases to a
      growth hormone (GH) secreting pituitary adenoma. Its clinical manifestations are
      associated to local complications related to the tumor growth and/or to the
      metabolic consequences of GH excess. We report here our experience on 154
      acromegalic patients. Surgical remission rate using stringent biochemical
      criteria was 32%, a figure relatively low due to the great number of patients
      bearing macroadenomas with invasive complications. Primary or adjuvant
      radiotherapy was able to obtain normalization of biochemical parameters in as
      much as 65.4% of treated patients. In only 14.0% of acromegalics drug therapy
      with dopaminergic agents was effective in controlling the disease. By contrast,
      somatostatinergic analogues were more effective, obtaining a clinical and
      biochemical remission in 45.7% of the patients. In summary, multimodal therapy of
      acromegaly can lead to a global safe control of the disease in 55.2% of the
      cases. The ongoing development of new drugs represents promising alternatives in
      the management of this disabling condition.

PMID- 20679053
TI  - [Orbital and ocular adnexal lymphomas. Clinico-pathological correlation in 25
      cases].
AB  - Clinical, histological features and outcome of a cohort of patients with orbital
      and adnexal lymphoproliferative tumors were evaluated. Twenty-five cases in an
      oncologic referral center from 1995 to 2008, were included in the study. Each
      case had detailed immunophenotypic analysis using a panel of monoclonal
      antibodies (CD45, CD20, CD3, CD5, CD23, BCL2, BCL6, BCL10, Ki67, CD30, CD15,
      BCL1, Kappa, Lambda, CD138). Lesions were classified by using WHO (2008)
      lymphomas classification. Twenty-three patients were found to have primary and
      two secondary lymphomas. Histological subtypes were: 16 patients with marginal
      zone B cell lymphoma of mucosa-associated lymphoid tissue (MALT) lymphoma, four
      diffuse large B cell lymphomas, two mantle cell lymphomas, two follicular
      lymphomas, and one Hodgkin lymphoma. Among the 25 patients studied, 22 had
      localized stage. Extranodal marginal zone lymphoma was the most frequent type of
      primary orbital and adnexal lymphoma. In this study localized disease was
      observed in most cases, and distant spread of the lymphomas was infrequent.

PMID- 20679054
TI  - [Atrial fibrillation in postoperative cardiac surgery. Prevalence and
      hospitalized period].
AB  - Atrial fibrillation is the most common heart rhythm disorder after cardiac
      surgery. In previous studies it has been associated with prolonged
      hospitalization, increased costs and mortality. This study aimed to determine the
      prevalence of postoperative atrial fibrillation in cardiac surgery and its impact
      on the hospitalization period. Medical records of consecutive patients undergoing
      cardiac surgery (coronary artery bypass graft, valvular, or both) between January
      2006 and November 2008 were included and retrospectively analyzed. Primary
      outcome was the presence of postoperative atrial fibrillation. The sample was
      divided into two groups, with and without atrial fibrillation in the
      postoperative. The clinical variables and length of hospital stay were compared
      between both groups. A total of 172 patients underwent surgery in this period.
      Seven patients were excluded from analysis due to lack of data. The mean age was
      64.2 +/- 9.5 years, and they were predominantly male. Atrial fibrillation was the
      most common complication (23.6%). The average length hospital stay was 6.7 +/-
      4.6 days. There were no significant differences between both groups, with atrial
      fibrillation (7.5 +/- 4.1 days), and without (6.5 +/- 4.7 days), p = 0.21. The
      presence of atrial fibrillation did not prolong hospitalization. Probably, such
      strategy of prevention would not be cost-effective.

PMID- 20679055
TI  - [Disease due to Mycobacterium simiae and "Mycobacterium sherrisii" in Argentina].
AB  - A revision of mycobacterial disease due to M simiae (n = 4) and "M. sherrisii" (n
      = 6) identified during an eight-year period is presented. Cases occurred among
      patients with AIDS (n = 6), previous history of silicosis (n = 2) or tuberculosis
      (n = 2). One case was lost to follow-up and the remaining nine responded poorly
      to chemotherapy based on clarithromycin, ethambutol and fluoroquinolones. Five
      patients died of whom four were HIV-positive, three remained chronic and one was
      cured. These microorganisms originated 2.1% of mycobacterioses cases detected in
      an eight-year period. Timely identification of this group of uncommon
      mycobacteria by molecular methods seems to be clinically relevant in order to
      warn of difficulties inherent to the treatment. However, the distinction between
      both closely related microorganisms might not be crucial for case management as
      no distinctive characteristics were evident among patients affected by M. simiae
      or "M. sherrisii".

PMID- 20679056
TI  - [Influence of sexual maturity and gonadectomy on cardiac electrical activity in
      male and female rabbits].
AB  - Sex-associated differences in cardiac electrical activity have already been
      document noted. Even though these differences are usually associated with the
      effect of maturity and sex hormones, there are still some controversial points to
      this respect. The aim of this study was to evaluate the effects of maturity and
      gonadectomy on the different parameters of surface electrocardiogram and the
      duration of the action potential in young and adult rabbits. The differences
      obtained in females were observed in late repolarization, whereas in males took
      place in early repolarization. There was a relationship between the differences
      observed in the duration from the peak to the end of the T wave and those
      observed in the duration of the action potential to 90% of repolarization in
      females, whereas in males the relationship exists between the duration from the
      point J to the peak of the T wave and the duration of the action potential at 30
      and 50% of repolarization. Differences could be related to hormonal or non
      hormonal factors.

PMID- 20679057
TI  - [Dog fouling and helminth contamination in parks and sidewalks of Buenos Aires
      City, 1991-2006].
AB  - The aim of this study was to provide data on canine fecal and helminthic
      contamination from parks and sidewalks in Buenos Aires City, collected by the
      Laboratory of General Parasitology, School of Sciences, University of Buenos
      Aires. A census of dog feces was performed in 1-11 parks per year between 1991
      and 2006, a single day each year. In the period 2000-2006, the census included
      feces on sidewalks surrounding the park. Thirty fresh fecal samples were randomly
      collected from each park to determine the presence of helminth eggs and fixed
      with 5% formalin until diagnosis by the Willis' flotation method with a saturated
      solution of NaCl. The 51 censuses showed a median of 288 feces/park and 82% of
      the feces were collected from grass or bare-ground areas. Fecal contamination in
      parks was higher between 2000/06 than in the previous period (p < 0.0000), and it
      increased with increasing human density on sidewalks surrounding the park (p
      =0.0076). The sidewalks showed a inverse pattern, with larger fecal contamination
      in the lesser densely populated areas (p =0.0000). All parks showed infected
      samples. The most frequent helminth genera were Ancylostoma (20.47%), Trichuris
      (2.59%) and Toxocara (1.70%). Our results indicated that an increase in dog
      number in addition to deficient public control policies accounted for the
      increase in dog fouling in public spaces of the city.

PMID- 20679058
TI  - [Interstitial cystitis. A challenge for the clinician].
AB  - Interstitial cystitis is characterized by over 6 months of chronic pain, pressure
      and discomfort felt in the lower pelvis or bladder. It is often relieved with
      voiding, along with daytime frequency and nocturia in the absence of an urinary
      tract infection. The disorder can be divided clinically into two groups 
      ulcerative and non-ulcerative- based on cystoscopic findings and response to
      treatment. Management follows an approach of applying the least invasive therapy
      that affords sufficient relief of symptoms. We report a case of a patient with
      interstitial cystitis. The diagnosis was performed by symptoms and lesion in the
      cystoscopy and excellent response to amitriptyline.

PMID- 20679059
TI  - [Serious and consecutive airway complications after lung transplantation].
AB  - Airway complications are relatively frequent after lung transplantation and
      represent a great challenge to the medical team. In spite of the development of
      different modalities of bronchoscopic treatment and a lower incidence of
      complications with new surgical techniques, morbidity and mortality are still
      elevated. We present the case of a woman who underwent right lung transplantation
      who afterward developed four severe and consecutive airway complications that
      solved with a successful therapy approach.

PMID- 20679060
TI  - [Sigmoid colon volvulus. Coffee bean sign].

PMID- 20679061
TI  - [Valve calcification in Werner's syndrome].

PMID- 20679062
TI  - [Atherogenic lipoprotein remnants in humans].
AB  - Remnant lipoproteins (RLPs) are the lipolytic product of triglycerides
      transported by very low density lipoproteins (VLDL) of hepatic and intestinal
      origin and intestinal chylomicrons. Lipoprotein lipase activity hydrolyse
      triglycerides in several steps, producing heterogeneous particles. Fasting plasma
      concentration in normolipidemic subjects is low, but it increases in post
      prandial states. Genetic alterations in Apo-E subtypes increases RLPs plasma
      concentration and produce dyslipoproteinemia phenotype. RLPs atherogenicity
      depends on their role as endothelial injuring factors, their impaired recognition
      by lipoprotein receptors, and their susceptibility to oxidative stress. They also
      promote the circulation of molecular adhesion molecules, the internalization in
      subendothelial macrophages via scavenger receptors and the accumulation in foam
      cells, all of them early mechanisms of atheromatosis. RLPs metabolism has been a
      subject of controversial studies. Their origin from different lipoproteins may
      explain their structural heterogeneity, therefore increasing the methodological
      difficulties to include RLPs in the atherogenic lipoprotein profile in the
      epidemiological studies of the field. Last advances on metabolism of RLPs and
      their emergent clinical role justifies an up dated revision of RLPs.

PMID- 20679064
TI  - [The oil spill and the cell membrane].

PMID- 20679063
TI  - [Health reform in the USA].
AB  - The United States of America passed early this year the bill enforcing their
      health reform. this reform aims at achieving universal insurance, cost
      containment and improving quality of care. The debate around this reform has been
      long and unable to arrive to an agreement between the parts. Even if the
      expansion in the medical coverage system does not reduce to zero the current
      degree of inaccessibility to the health system, these achievements could be
      considered a very important first step. Nonetheless, chances are that this reform
      will continue being as polemic as the negotiations previous to its conception.

PMID- 20679065
TI  - [Dictyostelium. A social amoeba as a model organism].

PMID- 20679066
TI  - [Biomedical literature. Quality not quantity].

PMID- 20679067
TI  - [Free of charge participation of patients in clinical trials].

PMID- 20679068
TI  - Cigarette smoking in relation to risk of ductal carcinoma in situ of the breast
      in a cohort of postmenopausal women.
AB  - In numerous studies, investigators have examined the association of active
      smoking with risk of invasive breast cancer, but to the authors' knowledge, no
      cohort study has assessed smoking in relation to the risk of in situ breast
      cancer, the postulated penultimate stage preceding invasive breast cancer. The
      authors examined the latter association using data collected at baseline from
      63,393 women in the Women's Health Initiative Clinical Trial. A total of 486
      cases of ductal carcinoma in situ (DCIS) of the breast were identified during 8
      years of follow-up between 1993 and 2005. Cox proportional hazards models were
      used to estimate hazard ratios and 95% confidence intervals. For the primary
      analysis, invasive breast cancer was treated as a competing risk. After
      adjustment for covariates, associations with smoking status, smoking intensity,
      duration, pack-years, and age at quitting were all close to the null value and
      showed few meaningful trends. Sensitivity analyses performed to address different
      possibilities with respect to the natural history of breast cancer also did not
      provide consistent evidence of an association of smoking with DCIS. The results
      of this large cohort study provide little support for an association of cigarette
      smoking with risk of DCIS in postmenopausal women.

PMID- 20679069
TI  - Influence of endogenous reproductive hormones on F2-isoprostane levels in
      premenopausal women: the BioCycle Study.
AB  - Endogenous reproductive hormones and oxidative stress have been independently
      linked to risk of chronic disease but mostly in postmenopausal women. The
      interplay between endogenous reproductive hormones and oxidative stress among
      premenopausal women, however, has yet to be clearly elucidated. The objective of
      this study was to investigate the association between endogenous reproductive
      hormones and F(2)-isoprostanes in the BioCycle Study. Women aged 18-44 years from
      western New York State were followed prospectively for up to 2 menstrual cycles
      (n = 259) during 2005-2007. Estradiol, progesterone, luteinizing hormone,
      follicle-stimulating hormone, sex hormone-binding globulin, F(2)-isoprostanes,
      and thiobarbituric acid-reactive substances were measured up to 8 times per cycle
      at clinic visits timed by using fertility monitors. F(2)-Isoprostane levels had
      an independent positive association with estradiol (beta = 0.02, 95% confidence
      interval: 0.01, 0.03) and inverse associations with sex hormone-binding globulin
      and follicle-stimulating hormone (beta = -0.04, 95% confidence interval: -0.07, 
      0.003; beta = -0.02, 95% confidence interval: -0.03, -0.002, respectively) after
      adjustment for age, race, age at menarche, gamma-tocopherol, beta-carotene, total
      cholesterol, and homocysteine by inverse probability weighting. Thiobarbituric
      acid-reactive substances, a less specific marker of oxidative stress, had similar
      associations. If F(2)-isoprostanes are specific markers of oxidative stress,
      these results call into question the commonly held hypothesis that endogenous
      estradiol reduces oxidative stress.

PMID- 20679070
TI  - Editorial: Be careful what you ask for: is the presence of IL-17 indicative of
      immunity?

PMID- 20679071
TI  - Editorial: PD-1, a new target for sepsis treatment: better late than never.

PMID- 20679072
TI  - Energetics of walking in elderly people: factors related to gait speed.
AB  - BACKGROUND: Slow walking speed in elderly people predicts increased morbidity and
      mortality. We examined factors that may be associated with decreased habitual
      walking speed in older men and women. METHODS: Older (range: 60-88 years, mean =
      72.5 years) men (n = 25) and women (n = 24) were recruited. The Short Physical
      Performance Battery, body composition, VO(2peak) on a treadmill, VO2 and rated
      perceived exertion during 10 minutes of walking at habitual gait speed and at a
      walking speed of 0.9 m/s, muscle strength, and level of physical activity were
      measured. RESULTS: VO(2peak) was strongly related to habitual gait speed (r =
      .744, p < .001) and remained significant even after controlling for age, muscle
      strength, and gender. Compared with the tertile of fastest walkers (mean gait
      speed, 1.37 +/- 0.04 m/s), the tertile of slowest walkers (0.87 +/- 0.02 m/s)
      were older (p < .001), shorter (p = .026), had lower lean body mass (p = .011),
      lower strength ( p < .001), less self-reported daily physical activity (p =
      .102), and higher relative (to VO(2peak)) intensity during walking at their
      habitual speed (65.3% +/- 3.9% vs 54.3% +/- 2.1% of VO(2peak), p = .013).
      CONCLUSIONS: VO(p2eak) was strongly associated with habitual walking speed,
      suggesting that as aerobic capacity declines with age, the exertion associated
      with habitual gait speed increases. A slowing of walking speed may be a response
      to increased perception of exertion. The extent to which exercise training
      affects habitual gait speed and fatigue is not clear.

PMID- 20679073
TI  - An ACE unit with a delirium room may improve function and equalize length of stay
      among older delirious medical inpatients.
AB  - BACKGROUND: Patients with delirium, compared with those without, are at increased
      risk for loss of function, longer hospital stays, and increased mortality. We
      studied the effect that an Acute Care of the Elderly Unit, which includes a
      delirium room, has on patients with delirium. METHODS: Retrospective
      observational study. Charts of 148 patients (>=65 years) admitted to an Acute
      Care of the Elderly Unit with a delirium room during a 4-month period were
      reviewed. Delirium on admission (prevalence) was based on physician-performed
      Confusion Assessment Method; delirium during hospital stay (incidence) was based
      on nurse-performed Confusion Assessment Method. Patients with delirium were
      compared with those without delirium regarding change in function between
      admission and discharge (activities of daily living), hospital length of stay,
      and mortality. RESULTS: The prevalence of delirium was 16.2% (24/148), and the
      incidence was 16.1% (20/124). There were no significant differences between
      delirious and non-delirious patients in demographics or comorbidity scores. A
      significant interaction effect (p < .001) indicated improved activities of daily
      living (mean +/- SD; scale 0-12) between admission and discharge among delirious
      patients (4.1 +/- 4.6 and 6.1 +/- 3.9) compared with non-delirious patients (7.4
      +/- 4.7 and 6.9 +/- 4.5). There were no differences between delirious and non
      delirious patients with reference to mean length of stay (6.4 +/- 3.1 vs 5.9 +/-
      3.6 days, respectively; p = .461) and mortality (2 [4.5%] versus 2 [1.9%],
      respectively; p = .582). CONCLUSIONS: Although this study sample was small, the
      results suggest that an Acute Care of the Elderly Unit with a delirium room may
      improve function among delirious patients and may equalize other outcomes
      compared with non-delirious patients.

PMID- 20679074
TI  - The midwife toad and Alma Mahler: epigenetics or a matter of deception?

PMID- 20679076
TI  - Challenging the global retinoblastoma survival disparity through a collaborative
      research effort.

PMID- 20679077
TI  - Corneal collagen crosslinking in post-LASIK keratectasia.
AB  - BACKGROUND/AIMS: To evaluate the effect of corneal collagen crosslinking with
      riboflavin and UV-A as a treatment option for postlaser in situ keratomileusis
      keratectasia. METHODS: Crosslinking was carried out in 22 eyes of 15 patients
      with iatrogenic keratectasia. Follow-up, according to a standardised protocol
      (uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), slit-lamp
      examination, pachymetry and topography), was performed preoperatively 1, 3, 6 and
      12 months after crosslinking. RESULTS: The mean BCVA was 0.19 (SD +/- 0.21)
      logMAR preoperatively, 0.25 (SD +/- 0.17) 1 month, 0.20 (SD +/- 0.20) 3 months,
      0.18 (SD +/- 0.21) 6 months and 0.15 (SD +/- 0.14) 12 months postoperatively
      (statistically significant postop1-postop6, p=0.0335). The maximum k-readings
      were 44.12 (SD +/- 3.97) preoperatively, 46.23 (SD +/- 4.14) 1 month, 43.88 (SD
      +/- 4.25) 3 months, 45.06 (SD +/- 5.07) 6 months and 44.43 (SD +/- 4.06) 12
      months postoperatively (statistically significant preop-postop1, p=0.0281).
      CONCLUSION: Crosslinking in patients with iatrogenic keratectasia stabilised the
      UCVA and BCVA as well as the maximum k-readings in our cohort. It seems to be a
      safe and promising procedure to stabilise the refraction and the corneal
      topography, and thus to stop the progression of visual loss, thereby avoiding or
      delaying disease progression and keratoplasty.

PMID- 20679078
TI  - Antimicrobial peptides expression by ocular surface cells in response to
      Acanthamoeba castellanii: an in vitro study.
AB  - AIMS: Antimicrobial peptides (AMPs) are natural effectors of the innate immune
      response. Much work has been done to study their response and effects on
      bacterial and viral infection. Little if any information is available in relation
      to protozoal infections. The aim of the study was to comprehensively study the
      gene expression of the ocular AMPs in human corneal limbal epithelial cells
      stimulated with Acanthamoeba castellanii (AC). METHODS: Human corneal limbal
      epithelial cells were exposed to AC at different time points, up to 9 h, the
      genomic profile of the AMPs were analysed at these time point using real time
      PCR. corneal limbal epithelial cells not infected with AC were used as controls.
      RESULTS: Seven of the eight studied AMPs showed statistically significant
      upregulation in gene expression. Human beta Defensin 3 (hBD3) showed a very
      significant 10-fold upregulation in the exposed cells and Ribonuclease-7 (RNase
      7) showed a very early and consistent increase. Human beta Defensin 1 (hBD1) was
      the only downregulated AMP. CONCLUSIONS: The study data suggests a possible role
      of the AMPs in combating the amoebic infection at the ocular surface. Using AMPs
      singly or in combination is a promising avenue for further exploration in the
      treatment of the sight threatening Acanthamoeba keratitis.

PMID- 20679079
TI  - Prospective study on ocular findings in acute Puumala hantavirus infection in
      hospitalised patients.
AB  - AIMS: To appraise the ocular manifestations of Puumala hantavirus evoked
      haemorrhagic fever with renal syndrome nephropathia epidemica (NE) and to clarify
      the mechanisms of ocular changes in the largest series of patients examined to
      date. METHODS: 92 eyes of 46 patients with serologically proven NE were examined
      during the acute phase and after clinical recovery. Ocular symptoms were
      recorded, and visual acuity, refraction, intraocular pressure and ocular
      dimensions were evaluated. RESULTS: 88% of the patients experienced decreased
      intraocular pressure (IOP) (p<0.001), 87% reduced visual acuity, 87% conjunctival
      chemosis, 82% thickening of the lens (p<0.05), 78% myopic shift (p<0.001), 64%
      shallowing of the anterior chamber (p<0.05) and 52% shallowing of vitreous length
      (p<0.05) during the acute phase compared with that measured after clinical
      recovery. In all, 70% of the patients reported ocular symptoms. CONCLUSION:
      Ocular symptoms and disturbances are common in acute NE, and the symmetry of the
      ocular changes reflects the systemic nature of the disease. A decrease in IOP and
      myopic shift mainly due to thickening of the lens are evident in acute disease.
      The myopic shift only partially explains the visual disturbances supporting the
      possible multifactorial origin of the ocular findings in patients with NE.

PMID- 20679080
TI  - Photodynamic therapy for steroid-associated central serous chorioretinopathy.
AB  - PURPOSE: To evaluate the short-term efficacy of photodynamic therapy (PDT) for
      steroid-associated chronic or recurrent central serous chorioretinopathy (CSC).
      DESIGN: Interventional case series. METHODS: Retrospective review of nine
      consecutive cases of steroid-associated CSC treated with PDT using half-fluence
      for fovea involving treatments (n=4) and full-fluence for extrafoveal treatments
      (n=5). The main outcome measures included anatomical changes measured on optical
      coherence tomography (OCT) and changes in best-corrected visual acuity (BCVA)
      after PDT. RESULTS: All eyes had fovea involving serous retinal detachment on
      OCT, and six (67%) eyes had a history of three or more recurrences. The mean
      duration of current episode of CSC prior to PDT was 45 months (range: 3-131
      months). The mean follow-up after PDT was 8 months (range: 3-18 months). Serous
      retinal detachment disappeared in all cases following PDT without any
      complications. One patient had a recurrence and was re-treated. Compared to the
      mean BCVA of 20/83 (logMAR 0.62) at baseline, the mean BCVA was 20/40 (logMAR
      0.33) at 3 months (p=0.018), and 20/47 (logMAR 0.37) at last follow up (p=0.075).
      Visual acuity improved by at least two lines in three (33%) eyes. CONCLUSIONS:
      Despite chronicity and recurrences seen in steroid-associated CSC, serous retinal
      detachment resolved in all cases, and a modest improvement in visual acuity was
      observed following PDT, at least for the short term. Given the difficulty of
      managing these cases, PDT as applied in this study may be an effective treatment.

PMID- 20679081
TI  - Distal enlargement of the optic nerve sheath in the hyperacute stage of
      intracerebral haemorrhage.
AB  - AIMS: Optic nerve sheath diameter (ONSD) enlargement is detectable in patients
      with increased intracranial pressure. The aim was to detect an enlargement of the
      ONSD using optic nerve sonography in patients with acute intracerebral
      haemorrhage (ICH) within 6 h of the onset of symptoms. METHODS: Thirty-one acute
      ICH patients, 15 age-matched acute ischaemic stroke patients and 16 age-matched
      healthy volunteers were enrolled consecutively in this prospective bi-centre
      observational study. All acute stroke patients underwent brain CT, optic nerve
      sonography and transcranial colour-coded duplex sonography (TCCS) at admission
      within 6 h of stroke onset. The ONSD both 3.0 and 12.0 mm behind the globe using
      optic nerve sonography were recorded and statistically evaluated, as were age,
      sex, haemorrhage volume and midline shift measured by CT, and blood flow
      velocities in both middle cerebral arteries using TCCS. RESULTS: In acute ICH
      patients, a significant enlargement of ONSD was detected (p < 0.0083). The best
      cut-off point to predict ICH volume >2.5 cm3 was the relative ONSD enlargement of
      > 0.66 mm (> 21 %), with 90.3% accuracy and kappa coefficient 0.760 (95% CI 0.509
      to 1.000). CONCLUSIONS: Sonographically measured enlargement of the ONSD may
      already be detectable in the hyperacute stage of increased intracranial pressure.

PMID- 20679082
TI  - Familial pattern of Salzmann-type nodular corneal degeneration--a four generation
      series.

PMID- 20679083
TI  - Incidence of recipient Descemet membrane remnants at the donor-to-stromal
      interface after descemetorhexis in endothelial keratoplasty.

PMID- 20679084
TI  - A comparative clinical trial of the efficacy of two different aqueous solutions
      of cyclosporine for the treatment of moderate-to-severe dry eye syndrome.
AB  - OBJECTIVE: To evaluate the efficacy and safety of two different concentrations of
      cyclosporine A (CsA) in aqueous solution compared to vehicle in patients with dry
      eye syndrome. DESIGN: Multicentre, randomised, double-masked, vehicle-controlled,
      clinical trial. METHODS: A total of 183 patients were enrolled and randomised to
      either CsA 1% (group A), CsA 0.05% (group B) or vehicle only (group C). The main
      objective was to evaluate the efficacy of CsA aqueous solution in the reduction
      of signs and symptoms in patients with moderate to severe dry eye disease.
      RESULTS: An early (day 21) statistically significant improvement (p<0.05) was
      evident in four symptoms and three ocular signs in group A. An equivalent
      improvement in three symptoms and three ocular signs was demonstrated in group B.
      A significant improvement was identified in two symptoms and two ocular signs in
      group C. Comparing the three groups together, group A performed better in four
      symptoms than group B did with just one symptom. Group C did not show significant
      improvement. At day 42, group A showed improvement in four symptoms, while group
      B showed improvement in one symptom and one ocular sign. CONCLUSIONS:
      Cyclosporine A reduced complaints and improved major ocular signs in patients
      with moderate-to-severe dry eye disease. The group treated with the 0.1%
      cyclosporine A aqueous solution outperformed the other groups.

PMID- 20679086
TI  - Diagnosis of microbial keratitis.

PMID- 20679087
TI  - Variations in amniotic membrane: relevance for clinical applications.

PMID- 20679089
TI  - Results of bevacizumab as the primary treatment for retinal vein occlusions.
AB  - BACKGROUND: The purpose of this study is to evaluate the efficacy of intravitreal
      bevacizumab as the primary treatment of macular oedema due to retinal vein
      occlusions. METHODS: Patients diagnosed as having central retinal vein occlusion
      (CRVO) or branch retinal vein occlusion (BRVO) with visual acuity of less than
      20/40 and macular oedema with more than 300 microm central retinal thickness were
      recruited. Patients that had received any prior treatment were excluded. After an
      initial intravitreal injection of bevacizumab, re-treatment was performed if
      intraretinal or subretinal fluid with distortion of the foveal depression was
      found in optical coherence tomography. RESULTS: 18 eyes with CRVO and 28 eyes
      with BRVO were included. During a 6-month period, the mean number of injections
      per patient was 3.7 (BRVO group) and 4.6 (CRVO group). In the BRVO group, mean
      baseline logMAR visual acuity was 0.80 (SD 0.38) and macular thickness was 486.9
      microm (SD 138.5 microm). After 6 months, mean logMAR visual acuity improved
      significantly to 0.44 (SD 0.34), p<0.001. Mean macular thickness decreased
      significantly to 268.2 microm (SD 62.5 microm), p<0.001. In the CRVO group, mean
      baseline logMAR visual acuity was 1.13 (SD 0.21) and macular thickness was 536.4
      microm (SD 107.1 microm). Mean final logMAR visual acuity improved significantly
      to 0.83 (SD 0.45), p<0.001. Mean macular thickness decreased significantly to
      326.17 microm (SD 96.70 microm), p<0.001. CONCLUSIONS: Intravitreal bevacizumab
      seems to be an effective primary treatment option for macular oedema due to
      retinal occlusions. Its main drawback is that multiple injections are necessary
      to maintain visual and anatomic improvements.

PMID- 20679090
TI  - An unusual intracameral precipitation after trabeculectomy.

PMID- 20679091
TI  - Functional and morphological macular abnormalities in membranoproliferative
      glomerulonephritis type II.

PMID- 20679092
TI  - Evolution of the actin gene family in testate lobose amoebae (Arcellinida) is
      characterized by two distinct clades of paralogs and recent independent
      expansions.
AB  - The evolution of actin gene families is characterized by independent expansions
      and contractions across the eukaryotic tree of life. Here, we assess diversity of
      actin gene sequences within three lineages of the genus Arcella, a free-living
      testate (shelled) amoeba in the Arcellinida. We established four clonal lines of
      two morphospecies, Arcella hemisphaerica and A. vulgaris, and assessed their
      phylogenetic relationship within the "Amoebozoa" using small subunit ribosomal
      DNA (SSU-rDNA) genealogy. We determined that the two lines of A. hemisphaerica
      are identical in SSU-rDNA, while the two A. vulgaris are independent genetic
      lineages. Furthermore, we characterized multiple actin gene copies from all
      lineages. Analyses of the resulting sequences reveal numerous diverse actin
      genes, which differ mostly by synonymous substitutions. We estimate that the
      actin gene family contains 40-50 paralogous members in each lineage. None of the
      three independent lineages share the same paralog with another, and divergence
      between actins reaches 29% in contrast to just 2% in SSU-rDNA. Analyses of
      effective number of codons (ENC), compositional bias, recombination signatures,
      and genetic diversity in the context of a gene tree indicate that there are two
      groups of actins evolving with distinct patterns of molecular evolution. Within
      these groups, there have been multiple independent expansions of actin genes
      within each lineage. Together, these data suggest that the two groups are located
      in different regions of the Arcella genome. Furthermore, we compare the Arcella
      actin gene family with the relatively well-described gene family in the slime
      mold Dictyostelium discoideum and other members of the Amoebozoa clade. Overall
      patterns of molecular evolution are similar in Arcella and Dictyostelium.
      However, the separation of genes in two distinct groups coupled with recent
      expansion is characteristic of Arcella and might reflect an unusual pattern of
      gene family evolution in the lobose testate amoebae. We provide a model to
      account for both the existence of two distinct groups and the pattern of recent
      independent expansion leading to a large number of actins in each lineage.

PMID- 20679093
TI  - Characterizing the native codon usages of a genome: an axis projection approach.
AB  - Codon usage can provide insights into the nature of the genes in a genome. Genes
      that are "native" to a genome (have not been recently acquired by horizontal
      transfer) range in codon usage from a low-bias "typical" usage to a more biased
      "high-expression" usage characteristic of genes encoding abundant proteins. Genes
      that differ from these native codon usages are candidates for foreign genes that
      have been recently acquired by horizontal gene transfer. In this study, we
      present a method for characterizing the codon usages of native genes--both
      typical and highly expressed--within a genome. Each gene is evaluated relative to
      a half line (or axis) in a 59D space of codon usage. The axis begins at the modal
      codon usage, the usage that matches the largest number of genes in the genome,
      and it passes through a point representing the codon usage of a set of genes with
      expression-related bias. A gene whose codon usage matches (does not significantly
      differ from) a point on this axis is a candidate native gene, and the location of
      its projection onto the axis provides a general estimate of its expression level.
      A gene that differs significantly from all points on the axis is a candidate
      foreign gene. This automated approach offers significant improvements over
      existing methods. We illustrate this by analyzing the genomes of Pseudomonas
      aeruginosa PAO1 and Bacillus anthracis A0248, which can be difficult to analyze
      with commonly used methods due to their biased base compositions. Finally, we use
      this approach to measure the proportion of candidate foreign genes in 923
      bacterial and archaeal genomes. The organisms with the most homogeneous genomes
      (containing the fewest candidate foreign genes) are mostly endosymbionts and
      parasites, though with exceptions that include Pelagibacter ubique and
      Beutenbergia cavernae. The organisms with the most heterogeneous genomes
      (containing the most candidate foreign genes) include members of the genera
      Bacteroides, Corynebacterium, Desulfotalea, Neisseria, Xylella, and
      Thermobaculum.

PMID- 20679094
TI  - Duodenal mass in a patient with weight loss and liver dysfunction. Duodenal and
      liver sarcoidosis.

PMID- 20679095
TI  - Osteogenesis imperfecta: primary care.

PMID- 20679096
TI  - Shock.

PMID- 20679097
TI  - Stuffy nose.

PMID- 20679098
TI  - Wounds.

PMID- 20679099
TI  - Research and statistics: generalizability and how it relates to validity.

PMID- 20679100
TI  - Visual diagnosis: vaginal mass in a 16-month-old child.

PMID- 20679101
TI  - Index of suspicion. Superior mesenteric artery syndrome; psoas abscess;
      hypokalemic periodic paralysis.

PMID- 20679102
TI  - Newborn ventilation.

PMID- 20679103
TI  - Hepatitis A.

PMID- 20679104
TI  - Cooperation and deception: from evolution to mechanisms.
AB  - Nature is full of struggle, as predicted by the theory of evolution through
      natural selection, yet there are also paramount examples where individuals help
      each other. These instances of helping have been difficult to reconcile with
      Darwin's theory because it is not always obvious how individuals are working for
      their own direct benefit. Consequently, initial publications that offered
      solutions to subsets of the observed cases of helping, such as kin selection or
      reciprocity, are among the most influential and most cited papers in
      evolution/behavioural ecology. During the last few years, a wave of new studies
      and concepts has considerably advanced our understanding of the conditions under
      which individuals are selected to help others. On the empirical side, advances
      are due to stronger incorporation of the natural history of each study species
      and an emphasis on proximate questions regarding decision-making processes. In
      parallel, theorists have provided more realistic models together with an
      increased exploration of the importance of life history and ecology in
      understanding cooperation. The ideas presented by the authors of this volume
      represent, in many ways, the revolutionary new approach to studying behaviour
      which is currently underway.

PMID- 20679105
TI  - How life history and demography promote or inhibit the evolution of helping
      behaviours.
AB  - In natural populations, dispersal tends to be limited so that individuals are in
      local competition with their neighbours. As a consequence, most behaviours tend
      to have a social component, e.g. they can be selfish, spiteful, cooperative or
      altruistic as usually considered in social evolutionary theory. How social
      behaviours translate into fitness costs and benefits depends considerably on life
      history features, as well as on local demographic and ecological conditions. Over
      the last four decades, evolutionists have been able to explore many of the
      consequences of these factors for the evolution of social behaviours. In this
      paper, we first recall the main theoretical concepts required to understand
      social evolution. We then discuss how life history, demography and ecology
      promote or inhibit the evolution of helping behaviours, but the arguments
      developed for helping can be extended to essentially any social trait. The
      analysis suggests that, on a theoretical level, it is possible to contrast three
      critical benefit-to-cost ratios beyond which costly helping is selected for
      (three quantitative rules for the evolution of altruism). But comparison between
      theoretical results and empirical data has always been difficult in the
      literature, partly because of the perennial question of the scale at which
      relatedness should be measured under localized dispersal. We then provide three
      answers to this question.

PMID- 20679106
TI  - Cooperation for direct fitness benefits.
AB  - Studies of the evolution of helping have traditionally used the explanatory
      frameworks of reciprocity and altruism towards relatives, but recently there has
      been an increasing interest in other kinds of explanations. We review the success
      or otherwise of work investigating alternative processes and mechanisms, most of
      which fall under the heading of cooperation for direct benefits. We evaluate to
      what extent concepts such as by-product benefits, pseudo-reciprocity, sanctions
      and partner choice, markets and the build-up of cross-species spatial trait
      correlations have contributed to the study of the evolution of cooperation. We
      conclude that these alternative ideas are successful and show potential to
      further increase our understanding of cooperation. We also bring up the origin
      and role of common interest in the evolution of cooperation, including the
      appearance of organisms. We note that there are still unresolved questions about
      the main processes contributing to the evolution of common interest. Commenting
      on the broader significance of the recent developments, we argue that they
      represent a justified balancing of the importance given to different major
      hypotheses for the evolution of cooperation. This balancing is beneficial because
      it widens considerably the range of phenomena addressed and, crucially,
      encourages empirical testing of important theoretical alternatives.

PMID- 20679107
TI  - Variation and the response to variation as a basis for successful cooperation.
AB  - In applying game theory to problems in biology, differences between individuals
      are often ignored. In particular, when analysing the evolution of cooperation it
      is often implicitly assumed that ignoring variation will produce predictions that
      approximate the solution when differences are included. This need not be true. As
      we demonstrate, differences are not innocuous noise, but can fundamentally change
      the nature of a game. Even small amounts of variability can stabilize cooperation
      by, for example, maintaining the need to deal with cheaters. Differences promote
      the need to learn about others in an interaction, leading to contingent behaviour
      that can reduce conflict, and to negotiated outcomes that may or may not be more
      cooperative than unconditional actions. Once there are mechanisms such as
      mutation and environmental influences that maintain variation within populations,
      whether cooperation evolves may depend on the variation in the cooperativeness
      trait. Variation means that it may be worth taking a chance that a partner is
      cooperative by being cooperative. When there are markets, so that individuals can
      break off interactions to seek a better partner, variation promotes choosiness
      and hence penalizes those uncooperative individuals, who are rejected. Variation
      promotes the need to monitor the previous behaviour of others, and once this
      social sensitivity exists, the need to maintain a good reputation can promote
      cooperation.

PMID- 20679108
TI  - Punishment and spite, the dark side of cooperation.
AB  - Causing harm to others would hardly seem to be relevant to cooperation, other
      than as a barrier to it. However, because selfish individuals will exploit
      cooperators, functional punishment is an effective mechanism for enforcing
      cooperation by deterring free-riding. Although functional punishment can shape
      the social behaviour of others by targeting non-cooperative behaviour, it can
      also intimidate others into doing almost anything. Second-party functional
      punishment is a self-serving behaviour at the disposal of dominant individuals
      who can coerce others into behaving cooperatively, but it need not do so. Third
      party and altruistic functional punishment are less likely to be selfishly
      motivated and would seem more likely to maintain norms of cooperation in large
      groups. These forms of functional punishment may be an essential part of non-kin
      cooperation on a scale exhibited only by humans. While punitive sentiments might
      be the psychological force behind punitive behaviours, spiteful motives might
      also play an important role. Furthermore, functionally spiteful acts might not be
      maladaptive; reckoning gains relative to others rather than in absolute terms can
      lead to hyper-competitiveness, which might also be an important part of human
      cooperation, rather than just an ugly by-product.

PMID- 20679109
TI  - Culture and cooperation.
AB  - Does the cultural background influence the success with which genetically
      unrelated individuals cooperate in social dilemma situations? In this paper, we
      provide an answer by analysing the data of Herrmann et al. (2008a), who studied
      cooperation and punishment in 16 subject pools from six different world cultures
      (as classified by Inglehart & Baker (2000)). We use analysis of variance to
      disentangle the importance of cultural background relative to individual
      heterogeneity and group-level differences in cooperation. We find that culture
      has a substantial influence on the extent of cooperation, in addition to
      individual heterogeneity and group-level differences identified by previous
      research. The significance of this result is that cultural background has a
      substantial influence on cooperation in otherwise identical environments. This is
      particularly true in the presence of punishment opportunities.

PMID- 20679111
TI  - Social eavesdropping and the evolution of conditional cooperation and cheating
      strategies.
AB  - The response of bystanders to information available in their social environment
      can have a potent influence on the evolution of cooperation and signalling
      systems. In the presence of bystanders, individuals might be able to increase
      their payoff by exaggerating signals beyond their means (cheating) or investing
      to help others despite considerable costs. In doing so, animals can accrue
      immediate benefits by manipulating (or helping) individuals with whom they are
      currently interacting and delayed benefits by convincing bystanders that they are
      more fit or cooperative than perhaps is warranted. In this paper, I provide some
      illustrative examples of how bystanders could apply added positive selection
      pressure on both cooperative behaviour and dishonest signalling during courtship
      or conflict. I also discuss how the presence of bystanders might select for
      greater flexibility in behavioural strategies (e.g. conditional or condition
      dependence), which could maintain dishonesty at evolutionarily stable frequencies
      under some ecological conditions. By recognizing bystanders as a significant
      selection pressure, we might gain a more realistic approximation of what drives
      signalling and/or interaction dynamics in social animals.

PMID- 20679110
TI  - How is human cooperation different?
AB  - Although cooperation is a widespread phenomenon in nature, human cooperation
      exceeds that of all other species with regard to the scale and range of
      cooperative activities. Here we review and discuss differences between humans and
      non-humans in the strategies employed to maintain cooperation and control free
      riders. We distinguish forms of cooperative behaviour based on their influence on
      the immediate payoffs of actor and recipient. If the actor has immediate costs
      and only the recipient obtains immediate benefits, we term this investment. If
      the behaviour has immediate positive effects for both actor and recipient, we
      call this a self-serving mutually beneficial behaviour or mutual cooperation. We
      argue that humans, in contrast to all other species, employ a wider range of
      enforcement mechanisms, which allow higher levels of cooperation to evolve and
      stabilize among unrelated individuals and in large groups. We also discuss
      proximate mechanisms underlying cooperative behaviour and focus on our
      experimental work with humans and our closest primate relatives. Differences in
      the proximate mechanisms also seem to contribute to explaining humans' greater
      ability to cooperate and enforce cooperation.

PMID- 20679112
TI  - Cooperation beyond the dyad: on simple models and a complex society.
AB  - Players in Axelrod and Hamilton's model of cooperation were not only in a
      Prisoner's Dilemma, but by definition, they were also trapped in a dyad. But
      animals are rarely so restricted and even the option to interact with third
      parties allows individuals to escape from the Prisoner's Dilemma into a much more
      interesting and varied world of cooperation, from the apparently rare
      'parcelling' to the widespread phenomenon of market effects. Our understanding of
      by-product mutualism, pseudo-reciprocity and the snowdrift game is also enriched
      by thinking 'beyond the dyad'. The concepts of by-product mutualism and pseudo
      reciprocity force us to think again about our basic definitions of cooperative
      behaviour (behaviour by a single individual) and cooperation (the outcome of an
      interaction between two or more individuals). Reciprocity is surprisingly rare
      outside of humans, even among large-brained 'intelligent' birds and mammals. Are
      humans unique in having extensive cooperative interactions among non-kin and an
      integrated cognitive system for mediating reciprocity? Perhaps, but our best
      chance for finding a similar phenomenon may be in delphinids, which also live in
      large societies with extensive cooperative interactions among non-relatives. A
      system of nested male alliances in bottlenose dolphins illustrates the potential
      and difficulties of finding a complex system of cooperation close to our own.

PMID- 20679113
TI  - The interplay of cognition and cooperation.
AB  - Cooperation often involves behaviours that reduce immediate payoffs for actors.
      Delayed benefits have often been argued to pose problems for the evolution of
      cooperation because learning such contingencies may be difficult as partners may
      cheat in return. Therefore, the ability to achieve stable cooperation has often
      been linked to a species' cognitive abilities, which is in turn linked to the
      evolution of increasingly complex central nervous systems. However, in their
      famous 1981 paper, Axelrod and Hamilton stated that in principle even bacteria
      could play a tit-for-tat strategy in an iterated Prisoner's Dilemma. While to our
      knowledge this has not been documented, interspecific mutualisms are present in
      bacteria, plants and fungi. Moreover, many species which have evolved large
      brains in complex social environments lack convincing evidence in favour of
      reciprocity. What conditions must be fulfilled so that organisms with little to
      no brainpower, including plants and single-celled organisms, can, on average,
      gain benefits from interactions with partner species? On the other hand, what
      conditions favour the evolution of large brains and flexible behaviour, which
      includes the use of misinformation and so on? These questions are critical, as
      they begin to address why cognitive complexity would emerge when 'simple'
      cooperation is clearly sufficient in some cases. This paper spans the literature
      from bacteria to humans in our search for the key variables that link cooperation
      and deception to cognition.

PMID- 20679114
TI  - Prosocial primates: selfish and unselfish motivations.
AB  - Non-human primates are marked by well-developed prosocial and cooperative
      tendencies as reflected in the way they support each other in fights, hunt
      together, share food and console victims of aggression. The proximate motivation
      behind such behaviour is not to be confused with the ultimate reasons for its
      evolution. Even if a behaviour is ultimately self-serving, the motivation behind
      it may be genuinely unselfish. A sharp distinction needs to be drawn, therefore,
      between (i) altruistic and cooperative behaviour with knowable benefits to the
      actor, which may lead actors aware of these benefits to seek them by acting
      cooperatively or altruistically and (ii) altruistic behaviour that offers the
      actor no knowable rewards. The latter is the case if return benefits occur too
      unpredictably, too distantly in time or are of an indirect nature, such as
      increased inclusive fitness. The second category of behaviour can be explained
      only by assuming an altruistic impulse, which-as in humans-may be born from
      empathy with the recipient's need, pain or distress. Empathy, a proximate
      mechanism for prosocial behaviour that makes one individual share another's
      emotional state, is biased the way one would predict from evolutionary theories
      of cooperation (i.e. by kinship, social closeness and reciprocation). There is
      increasing evidence in non-human primates (and other mammals) for this proximate
      mechanism as well as for the unselfish, spontaneous nature of the resulting
      prosocial tendencies. This paper further reviews observational and experimental
      evidence for the reciprocity mechanisms that underlie cooperation among non
      relatives, for inequity aversion as a constraint on cooperation and on the way
      defection is dealt with.

PMID- 20679115
TI  - On the psychology of cooperation in humans and other primates: combining the
      natural history and experimental evidence of prosociality.
AB  - In any given species, cooperation involves prosocial acts that usually return a
      fitness benefit to the actor. These acts are produced by a set of psychological
      rules, which will be similar in related species if they have a similar natural
      history of cooperation. Prosocial acts can be (i) reactive, i.e. in response to
      specific stimuli, or (ii) proactive, i.e. occur in the absence of such stimuli.
      We propose that reactive prosocial acts reflect sensitivity to (i) signals or
      signs of need and (ii) the presence and size of an audience, as modified by (iii)
      social distance to the partner or partners. We examine the evidence for these
      elements in humans and other animals, especially non-human primates, based on the
      natural history of cooperation, quantified in the context of food sharing, and
      various experimental paradigms. The comparison suggests that humans share with
      their closest living relatives reactive responses to signals of need, but differ
      in sensitivity to signs of need and cues of being watched, as well as in the
      presence of proactive prosociality. We discuss ultimate explanations for these
      derived features, in particular the adoption of cooperative breeding as well as
      concern for reputation and costly signalling during human evolution.

PMID- 20679118
TI  - e-Science: past, present and future II.

PMID- 20679116
TI  - Hormonal mechanisms of cooperative behaviour.
AB  - Research on the diversity, evolution and stability of cooperative behaviour has
      generated a considerable body of work. As concepts simplify the real world,
      theoretical solutions are typically also simple. Real behaviour, in contrast, is
      often much more diverse. Such diversity, which is increasingly acknowledged to
      help in stabilizing cooperative outcomes, warrants detailed research about the
      proximate mechanisms underlying decision-making. Our aim here is to focus on the
      potential role of neuroendocrine mechanisms on the regulation of the expression
      of cooperative behaviour in vertebrates. We first provide a brief introduction
      into the neuroendocrine basis of social behaviour. We then evaluate how hormones
      may influence known cognitive modules that are involved in decision-making
      processes that may lead to cooperative behaviour. Based on this evaluation, we
      will discuss specific examples of how hormones may contribute to the variability
      of cooperative behaviour at three different levels: (i) within an individual;
      (ii) between individuals and (iii) between species. We hope that these ideas spur
      increased research on the behavioural endocrinology of cooperation.

PMID- 20679117
TI  - Evolutionary causes and consequences of consistent individual variation in
      cooperative behaviour.
AB  - Behaviour is typically regarded as among the most flexible of animal phenotypic
      traits. In particular, expression of cooperative behaviour is often assumed to be
      conditional upon the behaviours of others. This flexibility is a key component of
      many hypothesized mechanisms favouring the evolution of cooperative behaviour.
      However, evidence shows that cooperative behaviours are often less flexible than
      expected and that, in many species, individuals show consistent differences in
      the amount and type of cooperative and non-cooperative behaviours displayed. This
      phenomenon is known as 'animal personality' or a 'behavioural syndrome'. Animal
      personality is evolutionarily relevant, as it typically shows heritable variation
      and can entail fitness consequences, and hence, is subject to evolutionary
      change. Here, we review the empirical evidence for individual variation in
      cooperative behaviour across taxa, we examine the evolutionary processes that
      have been invoked to explain the existence of individual variation in cooperative
      behaviour and we discuss the consequences of consistent individual differences on
      the evolutionary stability of cooperation. We highlight that consistent
      individual variation in cooperativeness can both stabilize or disrupt cooperation
      in populations. We conclude that recognizing the existence of consistent
      individual differences in cooperativeness is essential for an understanding of
      the evolution and prevalence of cooperation.

PMID- 20679119
TI  - Global hydrology modelling and uncertainty: running multiple ensembles with a
      campus grid.
AB  - Uncertainties associated with the representation of various physical processes in
      global climate models (GCMs) mean that, when projections from GCMs are used in
      climate change impact studies, the uncertainty propagates through to the impact
      estimates. A complete treatment of this 'climate model structural uncertainty' is
      necessary so that decision-makers are presented with an uncertainty range around
      the impact estimates. This uncertainty is often underexplored owing to the human
      and computer processing time required to perform the numerous simulations. Here,
      we present a 189-member ensemble of global river runoff and water resource stress
      simulations that adequately address this uncertainty. Following several
      adaptations and modifications, the ensemble creation time has been reduced from
      750 h on a typical single-processor personal computer to 9 h of high-throughput
      computing on the University of Reading Campus Grid. Here, we outline the changes
      that had to be made to the hydrological impacts model and to the Campus Grid, and
      present the main results. We show that, although there is considerable
      uncertainty in both the magnitude and the sign of regional runoff changes across
      different GCMs with climate change, there is much less uncertainty in runoff
      changes for regions that experience large runoff increases (e.g. the high
      northern latitudes and Central Asia) and large runoff decreases (e.g. the
      Mediterranean). Furthermore, there is consensus that the percentage of the global
      population at risk to water resource stress will increase with climate change.

PMID- 20679120
TI  - Data sharing, small science and institutional repositories.
AB  - Results are presented from the Data Curation Profiles project research, on who is
      willing to share what data with whom and when. Emerging from scientists'
      discussions on sharing are several dimensions suggestive of the variation in both
      what it means 'to share' and how these processes are carried out. This research
      indicates that data curation services will need to accommodate a wide range of
      subdisciplinary data characteristics and sharing practices. As part of a larger
      set of strategies emerging across academic institutions, institutional
      repositories (IRs) will contribute to the stewardship and mobilization of
      scientific research data for e-Research and learning. There will be particular
      types of data that can be managed well in an IR context when characteristics and
      practices are well understood. Findings from this study elucidate scientists'
      views on 'sharable' forms of data-the particular representation that they view as
      most valued for reuse by others within their own research areas-and the
      anticipated duration for such reuse. Reported sharing incidents that provide
      insights into barriers to sharing and related concerns on data misuse are
      included.

PMID- 20679121
TI  - Adoption and use of Web 2.0 in scholarly communications.
AB  - Sharing research resources of different kinds, in new ways, and on an increasing
      scale, is a central element of the unfolding e-Research vision. Web 2.0 is seen
      as providing the technical platform to enable these new forms of scholarly
      communications. We report findings from a study of the use of Web 2.0 services by
      UK researchers and their use in novel forms of scholarly communication. We
      document the contours of adoption, the barriers and enablers, and the dynamics of
      innovation in Web services and scholarly practices. We conclude by considering
      the steps that different stakeholders might take to encourage greater
      experimentation and uptake.

PMID- 20679122
TI  - Privacy compliance and enforcement on European healthgrids: an approach through
      ontology.
AB  - The sharing of medical data between different healthcare organizations in Europe
      must comply with the legislation of the Member State where the data were
      originally collected. These legal requirements may differ from one state to
      another. Privacy requirements such as patient consent may be subject to
      conflicting conditions between different national frameworks as well as between
      different legal and ethical frameworks within a single Member State. These
      circumstances have made the compliance management process in European healthgrids
      very challenging. In this paper, we present an approach to tackle these issues by
      relying on several technologies in the semantic Web stack. Our work suggests a
      direct mapping from high-level legislation on privacy and data protection to
      operational-level privacy-aware controls. Additionally, we suggest an
      architecture for the enforcement of these controls on access control models
      adopted in healthgrid security infrastructures.

PMID- 20679123
TI  - Reconfiguring practice: the interdependence of experimental procedure and
      computing infrastructure in distributed earthquake engineering.
AB  - When transitioning local laboratory practices into distributed environments, the
      interdependent relationship between experimental procedure and the technologies
      used to execute experiments becomes highly visible and a focal point for system
      requirements. We present an analysis of ways in which this reciprocal
      relationship is reconfiguring laboratory practices in earthquake engineering as a
      new computing infrastructure is embedded within three laboratories in order to
      facilitate the execution of shared experiments across geographically distributed
      sites. The system has been developed as part of the UK Network for Earthquake
      Engineering Simulation e-Research project, which links together three earthquake
      engineering laboratories at the universities of Bristol, Cambridge and Oxford. We
      consider the ways in which researchers have successfully adapted their local
      laboratory practices through the modification of experimental procedure so that
      they may meet the challenges of coordinating distributed earthquake experiments.

PMID- 20679124
TI  - Understanding performance of distributed data-intensive applications.
AB  - Grids, clouds and cloud-like infrastructures are capable of supporting a broad
      range of data-intensive applications. There are interesting and unique
      performance issues that appear as the volume of data and degree of distribution
      increases. New scalable data-placement and management techniques, as well as
      novel approaches to determine the relative placement of data and computational
      workload, are required. We develop and study a genome sequence matching
      application that is simple to control and deploy, yet serves as a prototype of a
      data-intensive application. The application uses a SAGA-based implementation of
      the All-Pairs pattern. This paper aims to understand some of the factors that
      influence the performance of this application and the interplay of those factors.
      We also demonstrate how the SAGA approach can enable data-intensive applications
      to be extensible and interoperable over a range of infrastructure. This
      capability enables us to compare and contrast two different approaches for
      executing distributed data-intensive applications-simple application-level data
      placement heuristics versus distributed file systems.

PMID- 20679125
TI  - A new application for the Grid: muon ionization cooling for a Neutrino Factory.
AB  - The muon ionization cooling experiment (MICE) will demonstrate a new technique
      for reducing the transverse emittance of a beam of muon particles, which are a
      species of lepton heavier than the electron species, essential for the
      realization of a future Neutrino Factory research facility. The first use of the
      Grid within MICE was to run thousands of Monte Carlo simulations to determine the
      alignment and statistical errors associated with measurements in MICE, which are
      made at two points in space on a similar sample of particles. The results of this
      study quantified the effect of correlations between emittance measurements. As a
      consequence, it has been determined that an order of magnitude less muons are
      required to achieve the required statistical accuracy than assuming uncorrelated
      measurements. This first application of the Grid within the MICE experimental
      domain has yielded results that could significantly impact upon the necessary
      running time of the experiment.

PMID- 20679126
TI  - Towards a scalable, open-standards service for brokering cross-protocol data
      transfers across multiple sources and sinks.
AB  - Data Transfer Service (DTS) is an open-source project that is developing a
      document-centric message model for describing a bulk data transfer activity, with
      an accompanying set of loosely coupled and platform-independent components for
      brokering the transfer of data between a wide range of (potentially incompatible)
      storage resources as scheduled, fault-tolerant batch jobs. The architecture
      scales from small embedded deployments on a single computer to large distributed
      deployments through an expandable 'worker-node pool' controlled through message
      orientated middleware. Data access and transfer efficiency are maximized through
      the strategic placement of worker nodes at or between particular data
      sources/sinks. The design is inherently asynchronous, and, when third-party
      transfer is not available, it side-steps the bandwidth, concurrency and
      scalability limitations associated with buffering bytes directly through
      intermediary client applications. It aims to address geographical-topological
      deployment concerns by allowing service hosting to be either centralized (as part
      of a shared service) or confined to a single institution or domain. Established
      design patterns and open-source components are coupled with a proposal for a
      document-centric and open-standards-based messaging protocol. As part of the
      development of the message protocol, a bulk data copy activity document is
      proposed for the first time.

PMID- 20679127
TI  - Integrating distributed data sources with OGSA-DAI DQP and VIEWS.
AB  - OGSA-DAI (Open Grid Services Architecture Data Access and Integration) is a
      framework for building distributed data access and integration systems. Until
      recently, it lacked the built-in functionality that would allow easy creation of
      federations of distributed data sources. The latest release of the OGSA-DAI
      framework introduced the OGSA-DAI DQP (Distributed Query Processing) resource.
      The new resource encapsulates a distributed query processor, that is able to
      orchestrate distributed data sources when answering declarative user queries. The
      query processor has many extensibility points, making it easy to customize. We
      have also introduced a new OGSA-DAI Views resource that provides a flexible
      method for defining views over relational data. The interoperability of the two
      new resources, together with the flexibility of the OGSA-DAI framework, allows
      the building of highly customized data integration solutions.

PMID- 20679128
TI  - CARMEN: a practical approach to metadata management.
AB  - The Code Analysis Repository & Modelling for E-Neuroscience (CARMEN) project aims
      to enable broad sharing of resources, through the provision of a secure, online
      environment for storage and curation of data, analysis code and experimental
      protocols, together with the ability to execute data analysis. While the CARMEN
      system is initially focused on electrophysiology data, it is equally applicable
      to many domains outside neuroscience. Metadata are essential for a system such as
      CARMEN that has the potential to store thousands of data collections and analysis
      codes; without metadata, resource discovery, interpretation, evaluation and re
      use would be severely impeded. Therefore, when any resource (data, service or
      workflow) is added to the system, users must provide adequate descriptions. These
      descriptions form a metadata repository that is searchable to allow users to find
      any kind of resource held in the system, assuming that the user has appropriate
      access rights. This paper discusses and explores the project's approach to
      implementing such a metadata repository that meets both system requirements and
      user expectations. Initial approaches were refined after user evaluations, and a
      more practical approach was followed that better aligned with the aims of the
      users and the project as a whole.

PMID- 20679129
TI  - Adoption of e-Infrastructure services: configurations of practice.
AB  - This paper reports findings from a study of researchers and research-computing
      support staff. It explores examples of the social relations supporting the
      adoption, adaptation and domestication of e-Research technologies and e
      Infrastructures and makes recommendations for funding organizations, technology
      suppliers, service providers and institutions.

PMID- 20679130
TI  - Retaining volunteers in volunteer computing projects.
AB  - Volunteer computing projects (VCPs) have been set up by groups of scientists to
      recruit members of the public who are asked to donate spare capacity on their
      personal computers to the processing of scientific data or computationally
      intensive models. VCPs serve two purposes: to acquire significant computing
      capacity and to educate the public about science. A particular challenge for
      these scientists is the retention of volunteers as there is a very high drop-out
      rate. This paper develops recommendations for scientists and software engineers
      setting up or running VCPs regarding which strategies to pursue in order to
      improve volunteer retention rates. These recommendations are based on a
      qualitative study of volunteers in a VCP (climateprediction.net). A typology of
      volunteers has been developed, and three particularly important classes of
      volunteers are presented in this paper: for each type of volunteer, the
      particular benefits they offer to a project are described, and their motivations
      for continued participation in a VCP are identified and linked to particular
      strategies. In this way, those setting up a VCP can identify which types of
      volunteers they should be particularly keen to retain, and can then find
      recommendations to increase the retention rates of their target volunteers.

PMID- 20679131
TI  - The design and implementation of a workflow analysis tool.
AB  - Motivated by the use of scientific workflows as a user-oriented mechanism for
      building executable scientific data integration and analysis applications, this
      article introduces a framework and a set of associated methods for analysing the
      execution properties of scientific workflows. Our framework uses a number of
      formal modelling techniques to characterize the process and data behaviour of
      workflows and workflow components and to reason about their functional and
      execution properties. We use the framework to design the architecture of a
      customizable tool that can be used to analyse the key execution properties of
      scientific workflows at authoring stage. Our design is generic and can be applied
      to a wide variety of scientific workflow languages and systems, and is evaluated
      by building a prototype of the tool for the Discovery Net system. We demonstrate
      and discuss the utility of the framework and tool using workflows from a real
      world medical informatics study.

PMID- 20679132
TI  - User engagement by user-centred design in e-Health.
AB  - This paper describes the application of user-centred design (UCD) methods and a
      user engagement (UE) approach to a case study development of a visualization tool
      (ADVISES) to support epidemiological research. The combined UCD/UE approach
      consisted of scenario-based design, and analysis of the users' tasks and mental
      model of the domain. Prototyping and storyboarding techniques were used to
      explore design options with users as well as specifying functionality for two
      versions of the software to meet the needs of novice and expert users. An
      evaluation of the prototype was carried out to assess the extent to which the
      expert model would support public health professionals in their analysis
      activities. The results of the design exploration requirements analysis study are
      reported. The implications of scenario-based design exploration, participatory
      design and user engagement are discussed.

PMID- 20679133
TI  - Comparison between 3-Nitrooxyphenyl acetylsalicylate (NO-ASA) and O2
      (acetylsalicyloxymethyl)-1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate (NONO-ASA)
      as safe anti-inflammatory, analgesic, antipyretic, antioxidant prodrugs.
AB  - Chronic inflammation is an underlying etiological factor in carcinogenesis;
      nonsteroidal anti-inflammatory drugs (NSAIDs) and their chemically modified NO
      releasing prodrugs (NO-NSAIDs) are promising chemopreventive agents. The aim of
      this study was to conduct a head-to-head comparison between two NO-ASAs
      possessing different NO donor groups, an organic nitrate [3-nitrooxyphenyl
      acetylsalicylate (NO-ASA; NCX-4016)] and an N-diazeniumdiolate [NONO-ASA, O(2)-
      (acetylsalicyloxymethyl)-1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate (NONO-ASA;
      CVM-01)], as antiulcerogenic, analgesic, anti-inflammatory, and antipyretic
      agents. All drugs were administered orally at equimolar doses. For
      antiulcerogenic study, 6 h after administration, the number and size of
      hemorrhagic lesions in stomachs from euthanized animals were counted. Tissue
      samples were frozen for prostaglandin E(2) (PGE(2)), superoxide dismutase (SOD),
      and malondialdehyde determination. For anti-inflammatory study, 1 h after drug
      administration, the volume of carrageenan-induced rat paw edemas was measured for
      6 h. For antipyretic study, 1 h after dosing, fever was induced by
      intraperitoneal LPS, and body core temperatures measured for 5 h. For analgesic
      study, time-dependent analgesic effect of prodrugs was evaluated by carrageenan
      induced hyperalgesia. Drugs were administered 30 min after carrageenan. NO-ASA
      and NONO-ASA were equipotent as analgesic and anti-inflammatory agents but were
      better than aspirin. Despite a drastic reduction of PGE(2) in stomach tissue,
      both prodrugs were devoid of gastric side effects. Lipid peroxidation induced by
      aspirin was higher than that observed by prodrugs. SOD activity induced by both
      prodrugs was similar, but approximately 2-fold higher than that induced by
      aspirin. CVM-01 is as effective as NCX-4016 in anti-inflammatory, analgesic, and
      antipyretic assays in vivo, and it showed an equivalent safety profile in the
      stomach. These results underscore the use of N-diazeniumdiolate moieties in drug
      design.

PMID- 20679134
TI  - Human heme oxygenase-1 efficiently catabolizes heme in the absence of biliverdin
      reductase.
AB  - Heme oxygenase 1 (HO-1) uses molecular oxygen and electrons from NADPH cytochrome
      P450 reductase to convert heme to CO, ferrous iron, and biliverdin (BV).
      Enzymatic studies with the purified 30-kDa form of HO-1 routinely use a coupled
      assay containing biliverdin reductase (BVR), which converts BV to bilirubin (BR).
      BVR is believed to be required for optimal HO-1 activity. The goal of this study
      was to determine whether HO-1 activity could be monitored directly by following
      BV generation or iron release (using the ferrous iron chelator, ferrozine) in the
      absence of BVR. Using assays for each of the three end products, we found that HO
      1 activity was stimulated in the presence of catalase and comparable rates were
      measured with each assay. Absorbance scans revealed characteristic spectra for
      BR, BV, and/or the ferrozine-iron complex. The optimal conditions were slightly
      different for the direct and coupled assays. BSA activated the coupled but
      inhibited the direct assays, and the assays had different pH optima. By measuring
      the activity of BVR directly using BV as a substrate, these differences were
      attributed to different enzymatic properties of BVR and HO-1. Thus, BVR is not
      needed to measure the activity of HO-1 when catalase is present. In fact, the
      factors affecting catalysis by HO-1 are better understood using the direct assays
      because the coupled assay can be influenced by properties of BVR.

PMID- 20679135
TI  - Finger-in-glove sign in bronchial atresia.

PMID- 20679136
TI  - A baseline study of anticoagulant management in UK hospitals.
AB  - OBJECTIVES: To undertake a baseline study of the management of anticoagulants in
      order to allow later comparison of the impact of the National Patient Safety
      Agency (NPSA) patient safety alert (including a new patient held record)
      published in April 2007. METHODS: A multimethod study comprising semistructured
      interviews in 20 acute trusts and a telephone/email survey of general
      practitioners (GPs). RESULTS: The authors found a high degree of consensus
      concerning a number of problems in the management of anticoagulation services.
      Consultant haematologists and chief pharmacists expressed concern about the level
      of competence of junior medical and nursing staff and the quality of patient
      discharge from general inpatient wards. Patients were regularly discharged before
      being stabilised on Warfarin, pre-discharge information was not always given,
      patient-held records were not reliably completed nor follow-up arrangements made.
      At the ward level, there was some confusion about the responsibility for
      completing the yellow book on discharge and little awareness of the role of GPs
      in providing a monitoring service. GPs were largely dissatisfied with the quality
      of discharge information. CONCLUSION: The baseline data present a significant
      cause for concern in the management of warfarin prior to the publication of the
      NPSA safety alert.

PMID- 20679137
TI  - Impact of sample size on variation of adverse events and preventable adverse
      events: systematic review on epidemiology and contributing factors.
AB  - OBJECTIVES: To perform a systematic review of the frequency of (preventable)
      adverse events (AE/PAE) and to analyse contributing factors, such as sample size,
      settings, type of events, terminology, methods of collecting data and
      characteristics of study populations. REVIEW METHODS: Search of Medline and
      Embase from 1995 to 2007. Included were original papers with data on the
      frequency of AE or PAE, explicit definition of study population and information
      about methods of assessment. Results were included with percentages of patients
      having one or more AE/PAE. Extracted data enclosed contributing factors. Data
      were abstracted and analysed by two researchers independently. RESULTS: 156
      studies in 152 publications met our inclusion criteria. 144/156 studies reported
      AE, 55 PAE (43 both). Sample sizes ranged from 60 to 8,493,876 patients (median:
      1361 patients). The reported results for AE varied from 0.1% to 65.4%, and for
      PAE from 0.1% to 33.9%. Variation clearly decreased with increasing sample size.
      Estimates did not differ according to setting, type of event or terminology. In
      studies with fewer than 1000 patients, chart review prevailed, whereas surveys
      with more than 100,000 patients were based mainly on administrative data. No
      effect of patient characteristics was found. CONCLUSIONS: The funnel-shaped
      distribution of AE and PAE rates with sample size is a probable consequence of
      variation and can be taken as an indirect indicator of study validity. A
      contributing factor may be the method of data assessment. Further research is
      needed to explain the results when analysing data by types of event or
      terminology.

PMID- 20679138
TI  - Looking for an explanation for the low sign span. Is order involved?
AB  - Although signed and speech-based languages have a similar internal organization
      of verbal short-term memory, sign span is lower than word span. We investigated
      whether this is due to the fact that signs are not suited for serial recall, as
      proposed by Bavelier, Newport, Hall, Supalla, and Boutla (2008. Ordered short
      term memory differs in signers and speakers: Implications for models of short
      term memory. Cognition, 107, 433-459). We administered a serial recall task with
      stimuli in Italian Sign Language to 12 deaf people, and we compared their
      performance with that of twelve age-, gender-, and education-matched hearing
      participants who performed the task in Italian. The results do not offer evidence
      for the hypothesis that serial order per se is a detrimental factor for deaf
      participants. An alternative explanation for the lower sign span based on signs
      being phonologically heavier than words is considered.

PMID- 20679139
TI  - Patients repeatedly referred to secondary care with symptoms unexplained by
      organic disease: prevalence, characteristics and referral pattern.
AB  - BACKGROUND: Patients with medically unexplained symptoms (MUS) are commonly
      referred to specialist clinics. Repeated referrals suggest unmet patient need and
      inefficient use of resources. OBJECTIVES: How often does this happen, who are the
      patients and how are they referred? METHODS: The design of the study is a case
      control survey. The setting of the study is five general practices in Scotland,
      UK. The cases were 193 adults with three or more referrals over 5 years, at least
      two of which resulted in a diagnosis of MUS. The controls were (i) patients
      referred only once over 5 years and (ii) patients with three or more referrals
      with symptoms always diagnosed as medically explained. The measures of the study
      are SF-12 physical and mental component summaries; symptom count; and number of
      referrals, number of different GPs who had referred and number of specialist
      follow-up appointments. RESULTS: A total of 1.1% [95% confidence interval (CI)
      1.0-1.2%] of patients had repeated (median 3, range 2-6) referrals with MUS.
      Compared to infrequently referred controls, they were older and more likely to be
      female, living alone and unemployed. Compared to controls with medically
      explained symptoms, their health status was comparable or worse: odds ratio for
      SF-12 physical component summary<40, 1.2 (95% CI 0.72-2.0); SF-12 mental
      component summary<40, 1.8 (95% CI 1.1-3.0); reporting eight or more physical
      symptoms, 2.2 (95% CI 1.2-3.8). They were referred by more GPs and received less
      specialist follow-up. CONCLUSIONS: A small proportion of primary care patients
      are repeatedly referred to specialist clinics where they receive multiple
      diagnoses of MUS. The needs of these patients and how they are managed merits
      greater attention.

PMID- 20679140
TI  - Neutralization of the extracellular HMGB1 released by ischaemic damaged renal
      cells protects against renal ischaemia-reperfusion injury.
AB  - BACKGROUND: Graft quality, comprised of ischaemia-reperfusion injury (IRI) and
      surgical manipulation, is one of the major factors influencing transplant
      rejection. High-mobility group box 1 (HMGB1), a known activator of innate
      immunity, has been associated with tissue-generated immunological 'danger'
      signals; however, its role in renal IRI is not clear. METHODS: Renal IRI was
      induced by clamping the left renal pedicle for 60 min in uninephrectomized BALB/c
      mice. Rabbit anti-mouse HMGB1 antibody was given intraperitoneally 24 h and 30
      min before renal ischaemia. Renal HMGB1 expression was assessed by
      immunohistochemistry and western blot. The therapeutic effect of HMGB1
      neutralizing antibody on IRI was evaluated in terms of renal function,
      histological and immunopathologic examination and terminal deoxynucleotidyl
      transferase-mediated uridine triphosphate nick end labelling assays. RESULTS:
      Ischaemia alone was associated with release of HMGB1, which after reperfusion
      appeared to induce localization of HMGB1 to renal tubules, peritubular
      capillaries and glomeruli where the renal cells might be more susceptible to
      ischaemic insult. Administration of blocking antibody to HMGB1 was associated
      with reduction in tubular apoptosis and inflammation (TNF-alpha expression) in
      situ and in vivo with preservation of renal function. CONCLUSIONS: These data
      suggest that released HMGB1 by ischaemic renal parenchyma cells may act as an
      essential early mediator in delayed inflammatory response during IRI, and
      targeting HMGB1 may represent a potential approach in the prevention of clinical
      IRI associated with kidney transplantation.

PMID- 20679141
TI  - Perceptions, knowledge, incentives, and barriers of brain donation among African
      American elders enrolled in an Alzheimer's research program.
AB  - PURPOSE: To learn about African American older adults' knowledge and perceptions
      of brain donation, factors that relate to participating or not participating in a
      brain donation research program, and methods to increase African American brain
      donation commitment rates in the context of an Alzheimer's disease (AD) research
      program. DESIGN AND METHODS: African American older adults (n = 15) from the
      Boston University Alzheimer's Disease Core Center participant research registry
      enrolled in 1 of 2 focus groups of 90 min about brain donation. Seven
      participants were selected for a third follow-up focus group. RESULTS: Focus
      group transcripts were analyzed using consensual qualitative research methods,
      and 8 overarching themes emerged: (a) perceptions of and misconceptions about
      brain donation procedures, (b) racial minorities in medical research, (c) racial
      disparities and discrimination in medical settings, (d) influence of religion and
      spirituality, (e) family perceptions of and involvement in donation, (f) family
      history of disease and desire to find a cure, (g) prior exposure to medical and
      research settings, and (h) culturally sensitive approaches to brain donation.
      IMPLICATIONS: Culturally relevant educational protocols need to be created for
      use with African American older adults. These protocols should include
      information about brain donation procedures, rates of AD among Black elders, and
      potential benefits of donation to Black communities; inclusion of religious
      figures, family, and peers in donation education and decisions; and methods to
      address mistrust, including cultural competence trainings for staff.

PMID- 20679142
TI  - Imbalanced dietary profile, anthropometry, and lipids in urban Asian Indian
      adolescents and young adults.
AB  - OBJECTIVE: To analyze the macronutrient, micronutrient, food intake pattern,
      anthropometry, and lipid profile of urban Asian Indian adolescents and young
      adults and compare it with the nutrient profile of rural Asian Indian and
      American adolescents. METHODS: This was a cross-sectional, epidemiologic
      descriptive study. Body mass index (BMI), percentage body fat, waist and hip
      circumferences, skinfold thickness, serum lipids, and dietary intake were
      assessed in 1236 subjects (607 males, 629 females) aged 13-25 years from schools
      and colleges of a metropolitan city of India. RESULTS: The mean age and BMI of
      study subjects were 17.6 +/- 2.4 years (range 13-25 years) and 19.8 +/- 3.3
      kg/m(2) (range 11.9-35.9 kg/m(2)), respectively. The mean daily percentages of
      total energy contributed by carbohydrates, total fats, proteins, saturated fatty
      acids (SFAs), monounsaturated fatty acids (MUFAs), polyunsaturated fatty acids
      (PUFAs), omega-3 PUFAs, omega-6 PUFAs, and trans-fatty acids for all subjects
      were 53%, 34%, 11%, 11%, 10%, 9%, 1%, 8%, and 0.3%, respectively. The absolute
      daily intake of total fat was 84 +/- 29 g/d in males and 72 +/- 21 g/d in
      females, which was approximately 4 times the recommended dietary allowance for
      Asian Indians (20-22 g/d). Among food groups, a high intake of milk, milk
      products, roots, and tubers was observed. In these young individuals, the
      prevalence of hypercholesterolemia (males > or =169 mg/dl; females > or =181
      mg/dl) and overweight (BMI > or =23.1 kg/m(2)) was 14.4% and approximately 16%,
      respectively. On comparison with rural Asian Indian adolescents, an
      inappropriately high intake of total fat was observed in our subjects. On the
      other hand, the percentage of energy intake of SFAs in Asian Indian and American
      adolescents was at par. CONCLUSIONS: High total fat and SFA intake and a low
      intake of MUFAs and omega-3 PUFAs showed imbalanced nutrition, which could be
      responsible for the increasing prevalence of obesity and insulin resistance in
      urban Asian Indian adolescents and young adults. Nutritional strategies for
      reducing SFA intake and balancing the omega-3/omega-6 PUFAs ratio should be
      urgently applied in Asian Indian adolescents and are also presented in this
      paper.

PMID- 20679143
TI  - Reduction of postprandial glycemia by the novel viscous polysaccharide PGX, in a
      dose-dependent manner, independent of food form.
AB  - OBJECTIVE: Health benefits of viscous fiber intake are well established;
      nevertheless few effective and palatable preparations are available. The
      objective of the study therefore was to determine palatability and effectiveness
      of escalating doses of PGX, a novel viscous polysaccharide (NVP), in reducing
      postprandial glycemia when added to a liquid and a solid meal. DESIGN: Two open
      label, randomized, controlled trials were undertaken. SETTING: Glycemic Index
      Laboratories, Inc, Toronto, Ontario, Canada. SUBJECTS: Two groups of 10 healthy
      subjects each (group 1: 5 M, 5 F; 35.6 +/- 13.2 y; 24.6 +/- 2.1 kg/m(2); and
      group 2: 3 M, 7 F; 33.5 +/- 11.1 y; 26.3 +/- 5.2 kg/m(2)) were studied.
      INTERVENTIONS: Zero, 2.5, 5, and 7.5 g of NVP were added to a glucose drink
      (group 1) or to white bread and margarine (WB + Marg) (group 2). Subjects
      repeated glucose control (group 1) or WB control (group 2) 3 times to allow
      calculation of the glycemic index (GI). Measures of Outcomes: Palatability of
      foods and capillary blood glucose concentrations were measured fasting and at 15,
      30, 45, 60, 90, and 120 minutes after the start of the meal. RESULTS: Addition of
      NVP to the meal reduced blood glucose incremental areas under the curve
      irrespective of dose, reaching significance at the 7.5 g dose when added to
      glucose (p < 0.01), and at the 5 and 7.5 g doses when added to WB + Marg (p <
      0.001). The GI values of glucose with 0, 2.5, 5, or 7.5 g of NVP were (mean +/-
      standard error of the mean [SEM]) 100.0 +/- 0.0, 83.7 +/- 9.0, 77.7 +/- 8.2, and
      72.5 +/- 5.9, respectively; the GI of the WB alone, or of WB + Marg, with 0, 2.5,
      5, or 7.5 g of NVP was 71.0 +/- 0.0, 66.8 +/- 3.0, 47.5 +/- 5.9, 37.3 +/- 5.9,
      and 33.9 +/- 3.6, respectively. CONCLUSION: Addition of NVP to different food
      matrices is highly effective in lowering the glycemic index of a food in a dose
      responsive manner.

PMID- 20679144
TI  - Magnesium intake and risk of self-reported type 2 diabetes among Japanese.
AB  - OBJECTIVE: Dietary magnesium intake has been associated with a reduced risk of
      type 2 diabetes in western populations, but the evidence is limited in Asian
      populations. METHODS: We assessed the relationship between dietary magnesium
      intake and risk of diabetes in a cohort of 17,592 individuals (6480 men and
      11,112 women) aged 40-65, free of a history of diabetes or other chronic disease
      at the time of the baseline lifestyle survey, who completed a 5-year follow-up
      questionnaire. Dietary magnesium was calculated by using a validated
      questionnaire, and the incidence of diabetes was defined by self-report of
      physician diagnosis. Associations between dietary magnesium and diabetes
      incidence were evaluated using a logistic regression model. RESULTS: We found 459
      self-reported new cases of diabetes (237 men and 222 women) at the 5-year follow
      up. Dietary intake of magnesium was inversely associated with age- and body mass
      index (BMI)-adjusted diabetes incidence in both sexes. In multivariable analysis
      that adjusted further for cardiovascular risk factors, the association was
      weakened in both sexes, but the association in total participants remained
      statistically significant. The odds ratios of diabetes with reference to the
      lowest quartile of magnesium intake were 0.83 (95% confidence interval [CI], 0.69
      to 1.09) for the second quartile, 0.79 (95% CI, 0.59 to 1.07) for the third
      quartile, and 0.64 (95% CI, 0.44 to 0.94) for the highest quartile of magnesium
      intake (p for trend = 0.04). CONCLUSIONS: Dietary intake of magnesium was
      associated with a reduced risk of type 2 diabetes in Japanese populations.

PMID- 20679145
TI  - Renal zinc clearance/glomerular filtration rate ratio as an indicator of marginal
      zinc deficiency associated with iron deficiency in childhood.
AB  - OBJECTIVE: To evaluate the usefulness of renal zinc clearance/glomerular
      filtration rate ratio (R(ClZn)/GFR) as an indicator of marginal zinc deficiency
      that is generally associated with iron deficiency in childhood. METHODS: Zinc
      status was evaluated in 36 iron-deficient children (22 boys and 14 girls) who
      ranged in age from 1 to 10 years using serum zinc concentration and U(Zn/Cr) and
      R(ClZn)/GFR ratios. The results were compared with the zinc status of 36 similar
      aged healthy children (24 boys and 12 girls). RESULTS: Serum zinc concentrations
      were 96.72 +/- 2.13 microg/dL and 93.93 +/- 1.95 microg/dL in iron-deficient and
      healthy subjects, respectively (p > 0.05). U(Zn/Cr) ratios were 0.54 +/- 0.04
      microg/mg and 0.88 +/- 0.04 microg/mg (p < 0.0001); R(ClZn)/GFR ratios were 2.27
      x 10(-3) +/- 0.20 and 3.32 x 10(-3) +/- 0.20 (p < 0.001) in iron-deficient and
      healthy subjects, respectively. Individual values of R(ClZn)/GFR and U(Zn/Cr)
      ratios correlated with hemoglobin (Hb) concentrations (r = 0.34, p < 0.01 and r =
      0.26, p < 0.05). Data grouped according to the ranges of Hb concentrations and
      R(ClZn)/GFR and U(Zn/Cr) ratios fit the following equations: The statistically
      significant difference in U(Zn/Cr) and R(ClZn)/GFR ratios between groups
      indicates decreased urinary estimation of marginal zinc deficiency, whereas no
      change was observed in serum zinc concentrations. According to the regression
      equation, it can be postulated that the R(ClZn)/GFR ratio is a linear function of
      Hb concentration and the U(Zn/Cr) ratio. CONCLUSION: R(ClZn)/GFR ratio was a
      reliable indicator for reduction in urinary zinc excretion; it estimated the
      marginal zinc deficiency associated with iron deficiency. The R(ClZn)/GFR ratio
      can be calculated using one sample of blood and urine; thus it could serve as an
      alternative indicator of marginal zinc deficiency, especially in routine health
      care.

PMID- 20679146
TI  - Satiating effect of a barley beta-glucan-enriched snack.
AB  - OBJECTIVE: Increasing viscous dietary fiber in snacks may have several
      nutritional advantages, especially for adolescents. Having a snack that may exert
      direct health benefits and that may, at the same time, contribute to the
      voluntary reduction of energy intake through modulation of appetite may be a
      useful dietary strategy for energy control in adolescence. In this short-term
      study, a new type of biscuit containing 5.2% barley beta-glucan was produced and
      its effect on appetite moods and food intake was investigated. METHODS: Twenty
      healthy adolescents were selected and randomly assigned to receive, as a
      midmorning snack, a 628 kJ (SP) or 1884 kJ (LP) preload of barley beta-glucan
      enriched (BB) or control (CB) biscuits. Appetite ratings before and within 2
      hours following the snack, as well as the energy intake at lunch, were recorded.
      RESULTS: For all sensations, a peak at 15 minutes post-snack and a subsequent
      return to baseline value were shown. A decrease of the area under the curve (AUC)
      of the desire to eat and an increase of the AUC of fullness and satiety were
      recorded with SP-BB compared to SP-CB. The energy intake recorded at the lunch
      test was always significantly lower than that at the control lunch only in
      females (3048 kJ vs. 3890 kJ) independently from the type of snack consumed.
      Total energy intake significantly correlated with preload values both in females
      and in males, but not with the type of biscuit. Nutritional composition of meals
      consumed ad libitum did not vary significantly from those with different
      preloads. CONCLUSIONS: The BB, consumed as a midmorning snack, although able to
      influence appetite ratings, did not modify food intake in a short time period.

PMID- 20679147
TI  - Randomized controlled trial of iron-fortified drinking water in preschool
      children.
AB  - OBJECTIVES: To evaluate the effects of fortified drinking water, with different
      concentrations of iron added, on hemoglobin and hematocrit values in
      preschoolers. METHODS: Double-blind, randomized cluster clinical trial, with
      children aged 2 to 5 years of age, from 4 state-run schools, forming 1 group for
      each school. For fortification, ferrous sulphate in concentrations of 5 mg of
      elemental iron per liter of water (group A), 7.5 mg (group B), and 10 mg (group
      C), was used during a period of 4 months. In group D, the control, a placebo
      (Bixa orellana) was added. Hemoglobin and hematocrit values were checked before
      and after intervention. RESULTS: Before fortification, hemoglobin and hematocrit
      averages were below the reference values adopted in all groups. After
      fortification, the prevalence of anemia showed a reduction in the 4 groups, which
      was more pronounced in group B, at 48.3%. The hemoglobin values in groups B
      (11.5) and C (11.4) were statistically similar. However, the average consumption
      of water/day/student was lower in group C. Comparison of hemoglobin values
      between groups A (11.2) and D (11.0) did not show a significant difference,
      suggesting insignificant efficacy with 5 mg Fe/L fortification. CONCLUSIONS: The
      consumption of drinking water fortified with 7.5 mg of elemental iron/L water
      resulted in greater adhesion and an increase in hemoglobin values, with a
      reduction in the prevalence of anemia.

PMID- 20679148
TI  - Higher protein intake is associated with diabetes risk in South Asian Indians:
      the Metabolic Syndrome and Atherosclerosis in South Asians Living in America
      (MASALA) study.
AB  - OBJECTIVE: Despite a high prevalence of type 2 diabetes in South Asian Indians,
      the impact of diet in this high-risk ethnic group has not been fully explored.
      The association of macronutrient intake and diabetes in South Asian Indians was
      examined in this cross-sectional study. METHODS: A population-based cohort of 146
      South Asian Indians aged 45-79 years without existing cardiovascular disease
      living in the San Francisco Bay Area was recruited between August 2006 and
      October 2007. Macronutrient intake was assessed with a food-frequency
      questionnaire developed and validated in South Asians. Diabetes was defined by
      use of a hypoglycemic medication, a fasting plasma glucose level > or =126 mg/dL,
      or a 2-hour post-challenge glucose level > or =200 mg/dL. The association between
      energy-adjusted macronutrient intake and diabetes was explored using
      multivariable logistic regression models. RESULTS: Forty-one (28%) participants
      had type 2 diabetes; 20 were unaware of this diagnosis and were classified as
      having diabetes by laboratory testing. In a model fully adjusted for age, sex,
      waist circumference, and hypertension, there was a 70% increase in the odds of
      diabetes per standard deviation in gram of protein intake/day (standardized OR
      1.70 [95% CI 1.08, 2.68], p = 0.02). There was a trend toward increased protein
      intake and diabetes in the subset of participants with previously unknown,
      laboratory-diagnosed diabetes. Results did not vary significantly by sex, body
      mass index, or dietary pattern. CONCLUSIONS: Higher level of protein intake was
      associated with increased odds of diabetes in this cohort of South Asian Indians.
      Diet may be a modifiable lifestyle factor in this high-risk ethnic group.

PMID- 20679149
TI  - Nutrition issues in the HIV-infected injection drug user: findings from the
      nutrition for healthy living cohort.
AB  - OBJECTIVE: The purpose of this paper is to highlight disparities between
      injection drug users (IDUs) and those who had never been IDUs from the Nutrition
      for Healthy Living (NFHL) cohort. Although IDUs were enrolled in the cohort
      throughout its duration, few analyses have sought to highlight findings specific
      to them. METHODS: NFHL, a prospective, longitudinal cohort conducted from 1995
      2005, included 881 human immunodeficiency virus (HIV) -infected men and women
      over the age of 18. Subjects were seen every 6 months; body composition and
      dietary and laboratory data were collected. Individuals were classified as
      current IDUs, past IDUs, and never-IDUs. The classification of ever-IDU combined
      current and past users. RESULTS: In NFHL, a higher proportion of ever-IDUs were
      women, African American, had a high school education or less, smoked, and were
      housing insecure and food insecure compared to never-IDUs. Ever-IDUs had lower
      total, soluble, and insoluble fiber and individual micronutrient intakes. A
      higher proportion of ever-IDUs had hepatitis C and HIV-related symptoms, used
      highly active antiretroviral therapy (HAART) less, and had a CD4 count <500
      cells/mm3, than never-IDUs, at the study endpoint. CONCLUSIONS: The course of HIV
      infection in past and current IDUs appears to be unique and requires more
      investigation. Physiologic and sociodemographic characteristics of IDUs
      contribute to poor disease management and nutritional status. Classic
      manifestations of HIV persist in IDUs in the HAART era.

PMID- 20679150
TI  - Is serum albumin a marker of malnutrition in chronic disease? The scleroderma
      paradigm.
AB  - BACKGROUND: Malnutrition is common in many chronic diseases, but physicians may
      rely on a low albumin value before deciding that malnutrition is present.
      OBJECTIVE: To determine the relationship between serum albumin and malnutrition
      in systemic sclerosis (SSc) as a paradigm for other chronic diseases. DESIGN:
      Cross-sectional, multicenter study of patients from the Canadian Scleroderma
      Research Group Registry. We used the Malnutrition Universal Screening Tool (MUST)
      to evaluate patients for malnutrition. Disease extent was measured in several
      ways, including physician global assessment. Multiple linear regression was
      performed to identify independent predictors of serum albumin. RESULTS: Two
      hundred fifty-eight patients were studied. The mean (SD) serum albumin level was
      44.4 (4.2) g/L. Only 2% of the values were below normal and all these patients
      were in MUST category > or =2, or high risk for malnutrition, which included
      21.3% of the cohort. MUST, shorter disease duration, greater disease severity
      (physician global assessment of disease severity and modified Rodnan skin score),
      and greater disease activity (physician global assessment of disease activity, C
      reactive protein, and Scleroderma Disease Activity Index) all correlated
      significantly but weakly with albumin. Multivariate analysis demonstrated that a
      higher MUST score and worse disease severity were independently associated with
      lower serum albumin, but only 7% of the variance of albumin was explained in the
      adjusted model. CONCLUSIONS: Serum albumin is not useful as a marker for
      malnutrition in SSc and should not be assumed to be useful as a marker in other
      chronic diseases. More attention should be paid to clinical features of
      malnutrition, including assessment of body mass index and unplanned weight loss,
      and overall disease severity.

PMID- 20679151
TI  - Milk enriched with conjugated linoleic acid fails to alter blood lipids or body
      composition in moderately overweight, borderline hyperlipidemic individuals.
AB  - BACKGROUND: Dietary conjugated linoleic acid (CLA) represents a group of
      positional and geometric isomers of conjugated dienoic derivatives of linoleic
      acid. The effects of dietary CLA on blood lipids and body composition in humans
      remain controversial. OBJECTIVE: To examine whether consumption of milk enriched
      naturally or synthetically with cis 9, trans 11 (c-9, t-11) and trans 10, cis 12
      (t-10, c-12) CLA isomers alters blood lipid indices, including concentrations of
      total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein
      cholesterol, and triacyglycerol; indices of liver function including plasma
      alanine transaminase and total bilirubin; C-reactive protein; tumor necrosis
      factor-alpha; and body weight and composition in moderately overweight,
      borderline hyperlipidemic humans. DESIGN: A randomized, 3-phase, crossover,
      single-blind clinical trial was carried out in moderately overweight, borderline
      hyperlipidemic individuals who consumed (1) milk naturally enriched in CLA (4.2%)
      containing c-9, t-11 only providing 1.3 g/d of CLA; (2) milk enriched with a 4.2%
      synthetic mixture of t-10, c-12 and c-9, t-11 CLA isomers providing 1.3 g/d of
      CLA; or (3) untreated milk as a control providing 0.2 g/d CLA. Dietary phases
      were each 8 weeks in duration and were separated by 4-week washout periods.
      Plasma lipid levels were measured in blood samples collected at the beginning and
      end of each dietary phase. Magnetic resonance imaging was carried out at the
      beginning and end of each dietary phase to assess any changes in regional body
      fat composition. RESULTS: Compared with the control intervention, consumption of
      the two CLA-enriched milks failed to alter plasma total cholesterol, low-density
      lipoprotein cholesterol, high-density lipoprotein cholesterol, or triacyglycerol
      concentrations; body weight; or fat composition. CLA consumption did not
      significantly affect plasma alanine transaminase, total bilirubin, C-reactive
      protein, or tumor necrosis factor-alpha concentrations. CONCLUSION: Results from
      this study fail to support the role of milk enriched naturally with CLA
      containing c-9, t-11 or synthetically with c-9, t-11 and t-10, c-12 CLA isomers
      in modulation of lipid profiles or body composition in moderately overweight,
      borderline hyperlipidemic individuals.

PMID- 20679153
TI  - An asymmetric stroop/reverse-stroop interference phenomenon in ADHD.
AB  - OBJECTIVE: To examine whether participants with ADHD showed a deficit in
      Stroop/reverse-Stroop interference by comparing them to non-ADHD participants.
      METHOD: A group with ADHD, primarily inattentive type (n = 15), and a paired non
      ADHD group (n = 15) completed the group version of the Stroop/reverse-Stroop
      test. RESULTS: Asymmetric interference was observed between the Stroop test and
      the reverse-Stroop test in ADHD participants, presenting evidence contrary to
      Barkley's behavioral inhibition model of ADHD in which response inhibition
      deficits pertained only to the ADHD-C subtype. CONCLUSION: Participants with ADHD
      showed a control deficit in reverse-Stroop interference but not in Stroop
      interference.

PMID- 20679152
TI  - Association among SNAP-25 gene DdeI and MnlI polymorphisms and hemodynamic
      changes during methylphenidate use: a functional near-infrared spectroscopy
      study.
AB  - OBJECTIVE: To investigate the interaction of treatment-related hemodynamic
      changes with genotype status for Synaptosomal associated protein 25 (SNAP-25)
      gene in participants with attention deficit hyperactivity disorder (ADHD) on and
      off single dose short-acting methylphenidate treatment with functional near
      infrared spectroscopy (fNIRS). METHOD: A total of 15 right-handed adults and 16
      right-handed children with DSM-IV diagnosis of ADHD were evaluated. Ten
      milligrams of short-acting methylphenidate was administered in a crossover
      design. RESULTS: Participants with SNAP-25 DdeI T/T genotype had decreased right
      deoxyhemoglobin ([HHb]) with treatment. SNAP-25 MnlI genotype was also associated
      with right deoxyhemoglobin ([HbO2]) and [HHb] changes as well as left [HHb]
      change. When the combinations of these genotypes were taken into account, the
      participants with [DdeI C/C or T/C and MnlI G/G or T/G] genotype had increased
      right [HHb] with MPH use whereas the participants with [DdeI T/T and MnlI T/T] or
      [DdeI T/T and MnlI G/G or T/G] genotypes had decreased right prefrontal [HHb].
      CONCLUSIONS: These results suggested that SNAP-25 polymorphism might be
      associated with methylphenidate induced brain hemodynamic changes in ADHD
      participants.

PMID- 20679154
TI  - College students with and without ADHD: comparison of self-report of medication
      usage, study habits, and academic achievement.
AB  - OBJECTIVE: To examine the relationship between ADHD medications, study habits,
      and academic achievement of ADHD-diagnosed undergraduates. METHOD: A total of 92
      students with a self-reported ADHD diagnosis and a current prescription for ADHD
      medication were compared with 143 control students in a survey of academic
      performance. RESULTS: Most ADHD students took stimulant medication and said the
      drugs helped them, yet believed they were worse than other students at planning
      and completing assignments and avoiding distractions. Although most study habits
      of ADHD students did not differ from controls, their high school and college GPA
      (grade point average), and ACT scores were significantly lower, and they withdrew
      from significantly more classes than did control students. Interestingly,
      preliminary data suggested that good study habits alone, even without stimulants,
      could overcome the achievement disparity of ADHD students. CONCLUSION: As
      previously shown for children and adolescents, stimulant medications alone did
      not eliminate the academic achievement deficit of ADHD undergraduates.

PMID- 20679155
TI  - Time estimation abilities of college students with ADHD.
AB  - OBJECTIVE: To evaluate the time estimation abilities of college students with
      ADHD on a novel, complex task that approximated academically oriented activities.
      METHOD: Totally 20 college students with ADHD were compared to a sample of 20 non
      ADHD students. Both groups completed a task, and scores were obtained for time to
      complete the task, errors made, prospective time estimate, confidence in
      estimate, and retrospective time estimate. In addition, scores were calculated
      for the difference between prospective estimate and actual time as well as the
      difference between retrospective estimate and actual time. RESULTS: Controlling
      for cognitive ability, the ADHD participants were significantly different from
      the non-ADHD participants on all dependent measures except confidence and errors.
      CONCLUSION: College students with ADHD showed retrospective time estimation
      difficulties that may be related to academic functioning in the college setting.

PMID- 20679157
TI  - Effect of pathological use of the internet on adolescent mental health: a
      prospective study.
AB  - OBJECTIVE: To examine the effect of pathological use of the Internet on the
      mental health, including anxiety and depression, of adolescents in China. It is
      hypothesized that pathological use of the Internet is detrimental to adolescents'
      mental health. DESIGN: A prospective study with a randomly generated cohort from
      the population. SETTING: High schools in Guangzhou, China. PARTICIPANTS:
      Adolescents aged between 13 and 18 years. MAIN EXPOSURE: Pathological use of the
      Internet was assessed using the Pathological Use of the Internet Test. OUTCOME
      MEASURES: Depression and anxiety were assessed by the Zung Depression and Anxiety
      Scales. RESULTS: After adjusting for potential confounding factors, the relative
      risk of depression for those who used the Internet pathologically was about 21/2
      times (incidence rate ratio,2.5;95%confidence interval,1.3-4.3) that of those who
      did not exhibit the targeted pathological internet use behaviors. No significant
      relationship between pathological use of the Internet and anxiety at follow-up
      was observed. CONCLUSIONS: Results suggested that young people who are initially
      free of mental health problems but use the Internet pathologically could develop
      depression as a consequence. These results have direct implications for the
      prevention of mental illness in young people, particularly in developing
      countries.

PMID- 20679156
TI  - Prevalence of attention deficit hyperactivity disorder and associated features
      among children in France.
AB  - BACKGROUND: Earlier studies point to the prevalence of attention deficit
      hyperactivity disorder (ADHD) to be similar around the world. There is, however,
      a wide variety in estimates. The prevalence of ADHD in youth has never been
      examined in France. METHOD: Starting with 18 million telephone numbers, 7,912
      numbers are randomly selected. Among the 4,186 eligible families, 1,012 (24.2%)
      are successfully recruited. A telephone interview is administered to all families
      about a child in the 6 to 12 age range. It covered family living situation,
      school performance, symptoms of ADHD, conduct disorder (CD), and oppositional
      defiant disorder (ODD), and other features of ADHD. RESULTS: The prevalence of
      ADHD in France is between 3.5% and 5.6%. The population prevalence of treatment
      for ADHD is 3.5%. ADHD youth are more likely to be men than women, and, compared
      to non-ADHD children, ADHD children are more likely to have CD and ODD. Having
      ADHD is associated with a family history of the disorder. The ADHD youth are more
      likely to have had learning difficulties, to have repeated a grade, and to be
      functioning academically below grade level. CONCLUSIONS: The epidemiology of ADHD
      in French children is similar to the epidemiology of ADHD in other countries. The
      disorder occurs in between 3.5% to 5.6% of youth and is more common among boys
      than among girls. The authors replicate the well-known association of ADHD with
      CD, ODD, and indices of school failure. The impact of ADHD symptoms on school
      performance highlights the importance of screening for such symptoms in schools.

PMID- 20679158
TI  - The plane truth.

PMID- 20679159
TI  - Assessing the palatability of oral rehydration solutions in school-aged children:
      a randomized crossover trial.
AB  - OBJECTIVE: To compare the palatability of 3 oral rehydration solutions. DESIGN:
      Prospective, blinded, randomized, 3-period, 3-treatment crossover trial. SETTING:
      Emergency department of a tertiary care pediatric hospital. PARTICIPANTS: Sixty
      six children aged 5 to 10 years with concerns unrelated to the gastrointestinal
      tract. Intervention Each participant consumed as much of each solution as they
      desired during a 15-minute period. MAIN OUTCOME MEASURES: The primary outcome was
      each child's rating of taste as measured on a 100-mm visual analog scale (worst
      taste, 0 mm; best taste, 100 mm). Secondary outcome measures were volume
      consumed, willingness to consume each liquid again, and the most favored liquid.
      RESULTS: All enrolled patients completed all 3 study periods. A significant
      carryover effect was detected for taste scores (P=.03), which were significantly
      different with and without adjustment for the carryover effect (P<.001).
      Unadjusted values were 65 mm for Pedialyte, 58 mm for Pediatric Electrolyte, and
      23 mm for Enfalyte. Differences in mean volume consumed were not significant
      (Enfalyte, 15 mL; Pediatric Electrolyte, 17 mL; and Pedialyte, 22 mL [P=.44]).
      The proportion of children who would drink each solution in the future varied
      significantly between Enfalyte and Pediatric Electrolyte (odds ratio, 0.22; 95%
      confidence interval, 0.11-0.46) and between Enfalyte and Pedialyte (0.38; 0.25
      0.57). There were differences in the identification of the best-tasting solution,
      with Pedialyte selected by 35 of 66 children (53%), Pediatric Electrolyte by 26
      of 66 children (39%), and Enfalyte by 5 of 66 children (8%) (P<.001). CONCLUSION:
      Sucralose-sweetened oral rehydration solutions (Pedialyte and Pediatric
      Electrolyte) were significantly more palatable than was a comparable rice-based
      solution (Enfalyte). Trial Registration clinicaltrials.gov Identifier:
      NCT00689312.

PMID- 20679160
TI  - Carryover bias in crossover trials.

PMID- 20679161
TI  - Malnutrition and hemodynamic status in adolescents hospitalized for anorexia
      nervosa.
AB  - OBJECTIVE: To determine the effects of malnutrition on hemodynamic status of
      adolescents hospitalized for anorexia nervosa. DESIGN: Longitudinal observational
      study. SETTING: Tertiary care pediatric hospital. Patients Thirty-eight
      adolescents with anorexia nervosa, aged 13 to 21 years, with a mean (SD) body
      mass index (calculated as weight in kilograms divided by height in meters
      squared) of 15.9 (1.8). Intervention Subjects received standard care, including
      bed rest and graded nutritional therapy. A subsample of subjects (n=19) returned
      11 to 57 weeks following hospitalization for a second cardiac evaluation. MAIN
      OUTCOME MEASURES: Results from a 15-lead electrocardiogram, echocardiogram,
      treadmill stress test, and spinal bone mineral density measurement. RESULTS: On
      admission, 26 subjects (68%) had sinus bradycardia. Bradycardia was less common
      in participants with a longer duration of illness (P=.04). Left ventricle mass
      was lower than predicted for age (Z score<-1.0) in 11 subjects (31%). Exercise
      tolerance was normal by all measures. Both heart rate and QT interval were
      predictors of spinal bone mineral density. In those who returned for follow-up,
      absolute measures of left ventricle mass did not change (P=.27). However, the
      corresponding Z scores declined over time (mean [SD] change, -0.9 [1.3]; P=.02).
      CONCLUSIONS: In acutely malnourished adolescents with anorexia nervosa, few truly
      pathologic cardiac findings were identified. Sinus bradycardia was observed in
      most cases. Mild reductions in left ventricle mass and left ventricle function
      were seen both at baseline and at follow-up, suggesting early sparing of cardiac
      muscle in the face of moderate malnutrition as well as a relative delay of
      cardiac muscle restoration. The association of hemodynamic status with altered
      spinal bone mineral density emphasizes the range of systems affected by
      malnutrition in anorexia nervosa.

PMID- 20679162
TI  - Diagnostic features of thyroid nodules in pediatrics.
AB  - OBJECTIVE: To investigate a cohort of pediatric patients with thyroid nodules,
      defining histotype frequency and differences between subjects with
      hyperthyroidism and euthyroidism and benign and malignant nodules. DESIGN:
      Retrospective cohort. SETTING: Consecutive cases from 9 Italian pediatric
      endocrinology centers for the last 10 years. Patients One hundred twenty
      pediatric patients with thyroid nodules. Intervention Doppler ultrasonography was
      performed in 71 subjects; scintiscan, in 56; fine-needle aspiration biopsy in
      104; and 63 underwent surgery. MAIN OUTCOME MEASURES: The differences in
      clinical, laboratory, and ultrasonographic data between patients with
      hyperthyroidism and euthyroidism and malignant and benign nodules were evaluated.
      RESULTS: One hundred fourteen patients had euthyroidism and 6, hyperthyroidism.
      The latter had more compressive signs (P=.003), greater nodule diameter (P=.02),
      intranodular vascularization pattern (P=.01), and increased scintiscan uptake
      (P<.001). Fine-needle aspiration biopsy disclosed benign lesions in 77 cases,
      malignant lesions in 19, and "suspicious" lesions in 8. Histologic examination
      disclosed 1 Hurthle cell and 5 follicular adenomas in patients with
      hyperthyroidism, whereas in patients with euthyroidism, 33 hyperplasic nodules,
      19 carcinomas (14 papillary, 3 follicular, and 2 medullary), 3 follicular and 1
      Hurthle cell adenoma, and 1 teratoma were detected. Nine patients had enhanced
      scintiscan uptake. Among the patients with euthyroidism, malignancies more
      frequently had palpable lymph nodes (P<.001), compressive signs (P=.004),
      microcalcifications (P<.001), intranodular vascularization (P=.01), and lymph
      node alterations (P<.001). CONCLUSIONS: The diagnosis of pediatric thyroid
      nodules should be based on a stepwise evaluation that includes clinical,
      laboratory, and radiographic modalities. While laboratory assessments establish
      thyroid function, ultrasonographic imaging identifies clinically unapparent
      nodules and provides detailed nodule characterization for suspected malignant
      lesions. Scintiscan in patients with hyperthyroidism and fine-needle aspiration
      biopsy in patients with euthyroidism represent the next logical step.

PMID- 20679163
TI  - Exhaled nitric oxide in acute respiratory syncytial virus bronchiolitis.
AB  - OBJECTIVE: To investigate fractional exhaled nitric oxide (FeNO) levels in
      infants during acute respiratory syncytial virus (RSV) bronchiolitis and during
      convalescence. DESIGN: Prospective cohort study. Comparison of FeNO levels
      between infants with laboratory-confirmed acute RSV bronchiolitis and 2 control
      groups: healthy infants and infants with recurrent wheezing. SETTING: The
      Department of Pediatric Emergency Medicine and the Pediatric Pulmonary Clinic of
      the Tel Aviv Medical Center from November 2008 to July 2009. The FeNO levels were
      measured at referral and at 2 visits over 4 months after convalescence. The FeNO
      level was measured using the multiple-breath exhalation technique. PARTICIPANTS:
      Forty-four infants with acute RSV bronchiolitis (mean [SD] age, 6.8 [7.3]
      months), 21 infants with recurrent wheezing (mean [SD] age, 10.8 [7.59] months),
      and 32 age-matched healthy controls (mean [SD] age, 6.8 [9.1] months). Follow-up
      data were available for 22 children (55%) for the first follow-up visit and for
      11 children (25%) for the second follow-up visit. EXPOSURE: Acute RSV
      bronchiolitis. MAIN OUTCOME MEASURES: The FeNO levels during acute RSV
      bronchiolitis vs controls and FeNO levels during follow-up vs acute-stage
      disease. RESULTS: Mean FeNO levels for RSV-positive infants were significantly
      lower compared with healthy controls and infants with recurrent wheezing: mean
      (SD), 1.89 (1.76) parts per billion (ppb), 7.28 (4.96) ppb, and 4.86 (7.49) ppb,
      respectively (P<.001). The FeNO levels at the 2- and 4-month follow-up visits
      increased to 7.74 (5.13) ppb and 11.37 (6.29) ppb, respectively (P=.001).
      CONCLUSIONS: The FeNO levels are temporarily reduced during acute RSV
      bronchiolitis and increase during convalescence to normal levels and higher. The
      mechanisms for this suppression and its relation to future wheezing and asthma
      need to be studied.

PMID- 20679164
TI  - Environmental factors associated with childhood-onset type 1 diabetes mellitus:
      an exploration of the hygiene and overload hypotheses.
AB  - OBJECTIVE: To assess the relationship between selected maternal and infant
      characteristics and risk of type 1 diabetes mellitus, specifically
      characteristics identified from birth records that may pertain to the hygiene or
      overload hypotheses. DESIGN: Population-based case-control study. SETTING:
      Washington State from 1987 to 2005. PARTICIPANTS: All children younger than 19
      years hospitalized for type 1 diabetes (International Classification of Diseases,
      Ninth Revision codes 250.x1 and 250.x3) identified (n=1852) from hospital
      discharge data and linked with their birth certificates. Controls (n=7408) were
      randomly selected from birth records, frequency matched on year of birth. MAIN
      EXPOSURES: Maternal factors included age, race, educational attainment, marital
      status, use of Medicaid insurance, body mass index, prepregnancy weight, prior
      births, timing and adequacy of prenatal care, and cesarean delivery. Infant
      factors included birth weight, size for gestational age, and gestational age.
      MAIN OUTCOME MEASURE: The main outcome was first hospitalization for type 1
      diabetes mellitus; adjusted odds ratios were estimated for the association of
      selected maternal and infant characteristics with type 1 diabetes. RESULTS:
      Consistent with the hygiene hypothesis, type 1 diabetes was negatively associated
      with having older siblings (for >or=3 siblings, odds ratio [OR], 0.56; 95%
      confidence interval [CI], 0.45-0.70) and with indicators of lower economic status
      or care access, such as an unmarried mother (OR, 0.79; 95% CI, 0.69-0.91),
      inadequate prenatal care (OR, 0.53; 95% CI, 0.40-0.71), or Medicaid insurance
      (OR, 0.67; 95% CI, 0.58-0.77). Related to the overload hypothesis, maternal body
      mass index of 30 or higher (OR, 1.29; 95% CI, 1.01-1.64) was associated with
      increased risk of diabetes. CONCLUSION: Environmental factors related to
      decreased antigenic stimulation in early life and maternal obesity may be
      associated with type 1 diabetes.

PMID- 20679165
TI  - Impact of a mentoring and skills group program on mental health outcomes for
      maltreated children in foster care.
AB  - OBJECTIVE: To evaluate the efficacy of the Fostering Healthy Futures program in
      reducing mental health problems and associated problems. DESIGN: Randomized
      controlled trial. SETTING: Denver metropolitan area. PARTICIPANTS: Children aged
      9 to 11 years who were maltreated and placed in foster care. INTERVENTION:
      Children in the control group (n=77) received an assessment of their cognitive,
      educational, and mental health functioning. Children in the intervention group
      (n=79) received the assessment and participated in a 9-month mentoring and skills
      group program. MAIN OUTCOME MEASURES: Children and caregivers were interviewed at
      baseline prior to randomization, immediately following the intervention, and 6
      months after the intervention. Teachers were interviewed 2 times after baseline.
      Measures included a multi-informant index of mental health problems, youth
      reported symptoms of posttraumatic stress, dissociation, and quality of life, and
      caregiver- and youth-reported use of mental health services and psychotropic
      medications. RESULTS: After adjusting for covariates, intent-to-treat analyses
      demonstrated that the treatment group had fewer mental health problems on a multi
      informant factor 6 months after the intervention (mean difference, -0.51; 95%
      confidence interval, -0.84 to -0.19), reported fewer symptoms of dissociation 6
      months after the intervention (mean difference, -3.66; 95% confidence interval, 
      6.58 to -0.74), and reported better quality of life immediately following the
      intervention (mean difference, 0.11; 95% confidence interval, 0.03 to 0.19).
      Fewer youths in the intervention group than in the control group had received
      recent mental health therapy 6 months after the intervention according to youth
      report (53% vs 71%, respectively; relative risk=0.75; 95% confidence interval,
      0.57 to 0.98). CONCLUSIONS: A 9-month mentoring and skills group intervention for
      children in foster care can be implemented with fidelity and high uptake rates,
      resulting in improved mental health outcomes. Trial Registration
      clinicaltrials.gov Identifier: NCT00809315.

PMID- 20679166
TI  - Intranasal midazolam vs rectal diazepam for the home treatment of acute seizures
      in pediatric patients with epilepsy.
AB  - OBJECTIVE: To compare intranasal midazolam, using a Mucosal Atomization Device
      (IN-MMAD), with rectal diazepam (RD) for the home treatment of seizures in
      children with epilepsy. DESIGN: Prospective randomized study. SETTING: Patients'
      homes and a freestanding children's hospital that serves as a referral center for
      5 states. PATIENTS: A total of 358 pediatric patients who visited a pediatric
      neurology clinic from July 2006 through September 2008 and were prescribed a home
      rescue medication for their next seizure. INTERVENTION: Caretakers were
      randomized to use either 0.2 mg/kg of IN-MMAD (maximum, 10 mg) or 0.3 to 0.5
      mg/kg of RD (maximum, 20 mg) at home for their child's next seizure if it lasted
      more than 5 minutes. OUTCOME MEASURES: The primary outcome measure was total
      seizure time after medication administration. Our secondary outcome measures were
      total seizure time, time to medication administration, respiratory complications,
      emergency medical service support, emergency department visits, hospitalizations,
      and caretakers' ease of administration and satisfaction with the medication.
      RESULTS: A total of 92 caretakers gave the study medication during a child's
      seizure (50 IN-MMAD, 42 RD). The median time from medication administration to
      seizure cessation for IN-MMAD was 1.3 minutes less than for RD (95% confidence
      interval, 0.0-3.5 minutes; P=.09). The median time to medication administration
      was 5.0 minutes for each group. No differences in complications were found
      between treatment groups. Caretakers were more satisfied with IN-MMAD and report
      that it was easier to give than RD. CONCLUSIONS: There was no detectable
      difference in efficacy between IN-MMAD and RD as a rescue medication for
      terminating seizures at home in pediatric patients with epilepsy. Ease of
      administration and overall satisfaction was higher with IN-MMAD compared with RD.
      Trial Registration clinicaltrials.gov Identifier: NCT00326612.

PMID- 20679167
TI  - Child hunger and long-term adverse consequences for health.
AB  - OBJECTIVE: To examine the effects of hunger, an extreme manifestation of food
      insecurity, on subsequent health outcomes using data from the Canadian National
      Longitudinal Survey of Children and Youth (NLSCY). DESIGN: Longitudinal survey,
      1994-2004/2005. SETTING: Canada. PARTICIPANTS: A total of 5809 children aged 10
      to 15 years and 3333 youth aged 16 to 21 years. MAIN EXPOSURES: Longitudinal
      survey data spanning a 10-year period were analyzed using logistic regression.
      Measures of hunger from NLSCY cycles 1 through 5 were used to differentiate
      participants who were ever hungry from those who were never hungry. A 3-level
      variable was created to assess the effect of repeated episodes of hunger.
      Covariates included participants' age, sex, baseline health, and household
      sociodemographic characteristics. Stratified models were used to examine the
      relation between hunger and health among boys and girls separately. OUTCOME
      MEASURES: The NLCSY cycle 6 outcomes included poor general health, chronic health
      conditions, and asthma. RESULTS: Among children, both ever being hungry and
      multiple episodes of hunger were associated with poorer general health but not
      with chronic conditions or asthma. Higher odds of chronic conditions and of
      asthma were observed among youth who experienced multiple episodes of hunger
      compared with those who were never hungry. Associations between hunger and poorer
      health outcomes persisted among girls in stratified analyses. CONCLUSIONS:
      Children and youth who experience hunger are more likely to have poorer health,
      and repeated exposure appears to be particularly toxic. Our findings point to the
      relevance of food insecurity in childhood as a marker of vulnerability, with
      implications for clinical practice and advocacy.

PMID- 20679169
TI  - Picture of the month--quiz case. Diagnosis: Nasal dermoid sinus cyst.

PMID- 20679168
TI  - Effects of unilateral clefts on brain structure.
AB  - OBJECTIVE: To evaluate potential abnormalities in brain structure of children and
      adolescents with unilateral clefts. DESIGN: Case-control study. SETTING: Tertiary
      care center. PARTICIPANTS: Boys aged 7 to 17 years with right (n=14) and left
      (n=19) clefts were compared with healthy age-matched boys (n=57). MAIN EXPOSURES:
      Structural brain measures were obtained using magnetic resonance imaging. OUTCOME
      MEASURE: It was explored whether laterality of clefts had a significant effect on
      brain structure. To this end, volumes of tissue types and various brain regions
      were evaluated. RESULTS: Total white matter was significantly lower in boys with
      right clefts compared with boys with left clefts and healthy boys. Gross regional
      analyses demonstrated that reductions in white matter were evident in both the
      cerebellum and the cerebrum in boys with right clefts. Furthermore, within the
      cerebrum, white matter volumes were particularly low in the frontal lobes and the
      occipital lobes. CONCLUSIONS: These preliminary results suggest that right clefts
      may be associated with more abnormalities in brain structure. More generally,
      laterality of a birth defect may have a significant effect on a developing
      organism.

PMID- 20679170
TI  - Rolling theme issue on comparative effectiveness research: the right treatment to
      the right patient at the right time.

PMID- 20679171
TI  - Child hunger, food insecurity, and social policy.

PMID- 20679172
TI  - Comorbid posttraumatic stress symptoms in an urban population of mothers
      screening positive for depression.

PMID- 20679173
TI  - Non-Hodgkin lymphoma survival among adolescents.

PMID- 20679174
TI  - Varicella vaccine refusal may not be bad.

PMID- 20679175
TI  - Advice for patients. Dehydration and oral rehydration.

PMID- 20679176
TI  - Dipeptidyl peptidase IV inhibition alters the hemodynamic response to angiotensin
      converting enzyme inhibition in humans with the metabolic syndrome.

PMID- 20679177
TI  - Essential hypertension, hypertension in pregnancy, and subsequent blood pressure:
      another old dilemma revisited.

PMID- 20679178
TI  - Breathing life into the lifecourse approach: pregnancy history and cardiovascular
      disease in women.

PMID- 20679179
TI  - Interactive hemodynamic effects of dipeptidyl peptidase-IV inhibition and
      angiotensin-converting enzyme inhibition in humans.
AB  - Dipeptidyl peptidase-IV inhibitors improve glucose homeostasis in type 2
      diabetics by inhibiting degradation of the incretin hormones. Dipeptidyl
      peptidase-IV inhibition also prevents the breakdown of the vasoconstrictor
      neuropeptide Y and, when angiotensin-converting enzyme (ACE) is inhibited,
      substance P. This study tested the hypothesis that dipeptidyl peptidase-IV
      inhibition would enhance the blood pressure response to acute ACE inhibition.
      Subjects with the metabolic syndrome were treated with 0 mg of enalapril (n=9), 5
      mg of enalapril (n=8), or 10 mg enalapril (n=7) after treatment with sitagliptin
      (100 mg/day for 5 days and matching placebo for 5 days) in a randomized, cross
      over fashion. Sitagliptin decreased serum dipeptidyl peptidase-IV activity
      (13.08+/-1.45 versus 30.28+/-1.76 nmol/mL/min during placebo; P<=0.001) and
      fasting blood glucose. Enalapril decreased ACE activity in a dose-dependent
      manner (P<0.001). Sitagliptin lowered blood pressure during enalapril (0 mg;
      P=0.02) and augmented the hypotensive response to 5 mg of enalapril (P=0.05). In
      contrast, sitagliptin attenuated the hypotensive response to 10 mg of enalapril
      (P=0.02). During sitagliptin, but not during placebo, 10 mg of enalapril
      significantly increased heart rate and plasma norepinephrine concentrations.
      There was no effect of 0 or 5 mg of enalapril on heart rate or norepinephrine
      after treatment with either sitagliptin or placebo. Sitagliptin enhanced the dose
      dependent effect of enalapril on renal blood flow. In summary, sitagliptin lowers
      blood pressure during placebo or submaximal ACE inhibition; sitagliptin activates
      the sympathetic nervous system to diminish hypotension when ACE is maximally
      inhibited. This study provides the first evidence for an interactive hemodynamic
      effect of dipeptidyl peptidase-IV and ACE inhibition in humans.

PMID- 20679180
TI  - Upregulation of ecto-5'-nucleotidase by rosuvastatin increases the vasodilator
      response to ischemia.
AB  - 3-Hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors (statins) are
      effective in the primary and secondary prevention of cardiovascular events.
      Although originally developed to improve lipid profile, statins have demonstrated
      a surplus of beneficial pleiotropic effects, including improved endothelial
      function, reduced inflammation, and increased tolerance to ischemia-reperfusion
      injury. In preclinical studies, increased ecto-5'-nucleotidase activity, the key
      enzyme in extracellular adenosine formation, plays an important role in these
      effects. Because human data are absent, we explored the effects of rosuvastatin
      on ecto-5'-nucleotidase activity and the clinical relevance of increased
      extracellular adenosine during ischemia in humans in vivo. The forearm
      vasodilator responses to 3 increasing periods of forearm ischemia (2, 5, and 13
      minutes) were determined during placebo and caffeine (an adenosine receptor
      antagonist) infusion into the brachial artery. At the end of an 8-day treatment
      period with rosuvastatin (20 mg per day), this whole procedure was repeated.
      During both experiments, ecto-5'-nucleotidase activity was determined.
      Vasodilator responses are expressed as the percentage increase in forearm blood
      flow ratio from baseline. Rosuvastatin increased ecto-5'-nucleotidase activity by
      49+/-17% and enhanced the vasodilator response after 2, 5, and 13 minutes of
      ischemia in the absence (146+/-19, 330+/-26, and 987+/-133 to 312+/-77, 566+/
      107, and 1533+/-267) but not in the presence of caffeine (98+/-25, 264+/-54, and
      727+/-111 versus 95+/-19, 205+/-34, and 530+/-62). Rosuvastatin increases
      extracellular formation of adenosine in humans in vivo probably by enhancing ecto
      5'-nucleotidase activity. This action results in the improvement of reactive
      hyperemia and may further enhance the clinical benefit of statins, in particular
      in conditions of ischemia.

PMID- 20679181
TI  - HDAC inhibition attenuates inflammatory, hypertrophic, and hypertensive responses
      in spontaneously hypertensive rats.
AB  - Reactive oxygen species and proinflammatory cytokines contribute to
      cardiovascular diseases. Inhibition of downstream transcription factors and gene
      modifiers of these components are key mediators of hypertensive response. Histone
      acetylases/deacetylases can modulate the gene expression of these hypertrophic
      and hypertensive components. Therefore, we hypothesized that long-term inhibition
      of histone deacetylase with valproic acid might attenuate hypertrophic and
      hypertensive responses by modulating reactive oxygen species and proinflammatory
      cytokines in SHR rats. Seven-week-old SHR and WKY rats were used in this study.
      Following baseline blood pressure measurement, rats were administered valproic
      acid in drinking water (0.71% wt/vol) or vehicle, with pressure measured weekly
      thereafter. Another set of rats were treated with hydralazine (25 mg/kg per day
      orally) to determine the pressure-independent effects of HDAC inhibition on
      hypertension. Following 20 weeks of treatment, heart function was measured using
      echocardiography, rats were euthanized, and heart tissue was collected for
      measurement of total reactive oxygen species, as well as proinflammatory
      cytokine, cardiac hypertrophic, and oxidative stress gene and protein
      expressions. Blood pressure, proinflammatory cytokines, hypertrophic markers, and
      reactive oxygen species were increased in SHR versus WKY rats. These changes were
      decreased in valproic acid-treated SHR rats, whereas hydralazine treatment only
      reduced blood pressure. These data indicate that long-term histone deacetylase
      inhibition, independent of the blood pressure response, reduces hypertrophic,
      proinflammatory, and hypertensive responses by decreasing reactive oxygen species
      and angiotensin II type1 receptor expression in the heart, demonstrating the
      importance of uncontrolled histone deacetylase activity in hypertension.

PMID- 20679182
TI  - Postmenopausal hypertension: role of the Renin-Angiotensin system.
AB  - After menopause, blood pressure increases in women. However, the underlying
      mechanisms responsible for postmenopausal hypertension are not completely
      understood. This study was conducted to determine the role that the renin
      angiotensin system (RAS) plays in post-menopausal hypertension. Post-estrous
      cycling (postmenopausal) spontaneously hypertensive rats or young female controls
      were treated with losartan, an angiotensin (Ang) II type 1 receptor blocker, for
      25 days. Mean arterial pressure was recorded continuously by radiotelemetry.
      Losartan significantly decreased blood pressure in postmenopausal rats and young
      female controls but failed to normalize blood pressure in postmenopausal rats to
      levels found in young controls. Plasma renin activity and plasma angiotensinogen
      were significantly elevated, and intrarenal Ang II type 1 receptor and renin mRNA
      expression were significantly downregulated in postmenopausal rats. Therefore,
      RAS only partially contributes to hypertension in postcycling spontaneously
      hypertensive rats, whereas hypertension in young females is mediated mainly by
      the RAS. The data suggest that other mechanisms besides activation of the RAS are
      likely involved in postmenopausal hypertension.

PMID- 20679183
TI  - Targeted genomic disruption of h-ras induces hypotension through a NO-cGMP-PKG
      pathway-dependent mechanism.
AB  - The aim of the present experiments was to evaluate the differences in arterial
      pressure between H-Ras lacking mice and control mice and to analyze the
      mechanisms involved in the genesis of the differences. H-Ras lacking mice and
      mouse embryonic fibroblasts from these animals were used. Blood pressure was
      measured using 3 different methods: direct intraarterial measurement in
      anesthetized animals, tail-cuff sphygmomanometer, and radiotelemetry. H-Ras
      lacking mice showed lower blood pressure than control animals. Moreover, the
      aorta protein content of endothelial nitric oxide synthase, soluble guanylyl
      cyclase, and cyclic guanosine monophosphate-dependent protein kinase was higher
      in H-Ras knockout mice than in control animals. The activity of these enzymes was
      increased, because urinary nitrite excretion, sodium nitroprusside-stimulated
      vascular cyclic guanosine monophosphate synthesis, and phosphorylated vasoactive
      stimulated phosphoprotein in aortic tissue increased in these animals.
      Furthermore, mouse embryonic fibroblasts from H-Ras lacking mice showed higher
      cyclic guanosine monophosphate-dependent protein kinase promoter activity than
      control cells. These results strongly support the upregulation of the nitric
      oxide-cyclic guanosine monophosphate pathway in H-Ras-deficient mice. Moreover,
      they suggest that H-Ras pathway could be considered as a therapeutic target for
      hypertension treatment.

PMID- 20679184
TI  - Experiences of immigrant women who self-petition under the Violence Against Women
      Act.
AB  - Undocumented immigrant women who are abused and living in the United States are
      isolated in a foreign country, in constant fear of deportation, and feel at the
      mercy of their spouse to gain legal status. To ensure that immigration law does
      not trap women in abusive relationships, the Violence Against Women Act (VAWA,
      1994) enabled immigrant women to self-petition for legal status. Qualitative
      research methods were used in this participatory action research to investigate
      the experiences of Mexican immigrant women filing VAWA self-petitions. Emotional,
      financial, and logistic barriers in applying are identified, and recommendations
      for practice research and policy are provided.

PMID- 20679185
TI  - "I am not [just] a rabbit who has a bunch of children!": agency in the midst of
      suffering at the intersections of global inequalities, gendered violence, and
      migration.
AB  - This article is based on an analysis of the life history narrative of Antonia, a
      Peruvian immigrant in Chile, in the context of ethnographic research on Chilean
      women's experiences of domestic violence (DV) and the post-dictatorship state's
      responses to DV. Structural and socio-cultural constraints and forms of violence,
      including global and local economic inequalities, migration, racism, and
      intimate, gender-based abuses in both home and receiving countries interact in
      Antonia's experience to produce suffering and influence a form of gendered
      agency. This analysis points to the need for research and policies specifically
      designed to attend to the intersecting vulnerabilities migrant women who suffer
      DV often face, as well as their agentive acts.

PMID- 20679186
TI  - Violence against women and natural disasters: findings from post-tsunami Sri
      Lanka.
AB  - This article presents a qualitative study of violence against women in post
      tsunami Sri Lanka. It examines the types of violence occurring throughout the
      disaster's emergency and later phases, and whether overall levels of violence
      increased. Explanatory factors and responses by different humanitarian actors are
      analyzed and recommendations made for future disaster management. It is argued
      that violence against women during natural disasters must be understood within
      the context of the violence against women that prevails in societies at "normal"
      times, which is exacerbated by disaster. Response therefore necessitates
      addressing both the social inequalities underlying women's vulnerability to
      violence and specific factors that "trigger" violence during disaster.

PMID- 20679187
TI  - Incapacitated rape and alcohol use in White and Asian American college women.
AB  - This study examined the role of Asian ethnicity as a moderator of drinking
      outcomes associated with alcohol-related sexual assault (incapacitated rape).
      Participants were 5,467 Asian American and White college women. Results found the
      overall MANOVA for ethnicity and incapacitated rape (IR) interactions to be
      significant. Asian American participants with no history of IR had fewer drinking
      problems than White American participants with no history of IR. Asian American
      participants with IR histories had more drinking problems than White Americans
      with IR histories. Findings indicate Asian Americans who experience IR may be at
      increased risk for negative alcohol outcomes.

PMID- 20679188
TI  - Fact or fiction? Gender issues related to newspaper reports of intimate partner
      homicide.
AB  - The present study compared newspaper articles reporting female-perpetrated
      intimate partner violence (IPV) homicides with those reporting male-perpetrated
      IPV homicides. Domestic violence was not mentioned in 72% of the articles. Female
      perpetrated IPV homicide, although relatively rare, was not portrayed as more
      newsworthy nor did it receive more coverage when compared to male-perpetrated IPV
      homicide. When analyzing explanations for homicides given in newspaper reports,
      as well as descriptors used to describe the perpetrator, there was no support
      found for gender bias in favor of male perpetrators. Female victims were more
      likely to be portrayed as innocent when compared to males.

PMID- 20679189
TI  - "How can I not?": men's pathways to involvement in anti-violence against women
      work.
AB  - Despite growing male participation in ending violence against women, little is
      known about the factors that precipitate men's engagement as antiviolence
      "allies." This study presents findings from a qualitative analysis of interviews
      with 27 men who recently initiated involvement in an organization or event
      dedicated to ending sexual or domestic violence. Findings suggest that men's
      engagement is a process that occurs over time, that happens largely through
      existing social networks, and that is influenced by exposure to sensitizing
      experiences, tangible involvement opportunities and specific types of meaning
      making related to violence. Implications for models of ally development and for
      efforts to engage men in antiviolence work are discussed.

PMID- 20679190
TI  - A major role for TLR8 in the recognition of vaccinia viral DNA by murine pDC?

PMID- 20679192
TI  - On ionic conduction in potassium channels.

PMID- 20679194
TI  - Agricultural management explains historic changes in regional soil carbon stocks.
AB  - Agriculture is considered to be among the economic sectors having the greatest
      greenhouse gas mitigation potential, largely via soil organic carbon (SOC)
      sequestration. However, it remains a challenge to accurately quantify SOC stock
      changes at regional to national scales. SOC stock changes resulting from SOC
      inventory systems are only available for a few countries and the trends vary
      widely between studies. Process-based models can provide insight in the drivers
      of SOC changes, but accurate input data are currently not available at these
      spatial scales. Here we use measurements from a soil inventory dating from the
      1960s and resampled in 2006 covering the major soil types and agricultural
      regions in Belgium together with region-specific land use and management data and
      a process-based model. The largest decreases in SOC stocks occurred in poorly
      drained grassland soils (clays and floodplain soils), consistent with drainage
      improvements since 1960. Large increases in SOC in well drained grassland soils
      appear to be a legacy effect of widespread conversion of cropland to grassland
      before 1960. SOC in cropland increased only in sandy lowland soils, driven by
      increasing manure additions. Modeled land use and management impacts accounted
      for more than 70% of the variation in observed SOC changes, and no bias could be
      demonstrated. There was no significant effect of climate trends since 1960 on
      observed SOC changes. SOC monitoring networks are being established in many
      countries. Our results demonstrate that detailed and long-term land management
      data are crucial to explain the observed SOC changes for such networks.

PMID- 20679195
TI  - Attenuation of age-related changes in mouse neuromuscular synapses by caloric
      restriction and exercise.
AB  - The cellular basis of age-related behavioral decline remains obscure but
      alterations in synapses are likely candidates. Accordingly, the beneficial
      effects on neural function of caloric restriction and exercise, which are among
      the most effective anti-aging treatments known, might also be mediated by
      synapses. As a starting point in testing these ideas, we studied the skeletal
      neuromuscular junction (NMJ), a large, accessible peripheral synapse. Comparison
      of NMJs in young adult and aged mice revealed a variety of age-related structural
      alterations, including axonal swellings, sprouting, synaptic detachment, partial
      or complete withdrawal of axons from some postsynaptic sites, and fragmentation
      of the postsynaptic specialization. Alterations were significant by 18 mo of age
      and severe by 24 mo. A life-long calorie-restricted diet significantly decreased
      the incidence of pre- and postsynaptic abnormalities in 24-mo-old mice and
      attenuated age-related loss of motor neurons and turnover of muscle fibers. One
      month of exercise (wheel running) in 22-mo-old mice also reduced age-related
      synaptic changes but had no effect on motor neuron number or muscle fiber
      turnover. Time-lapse imaging in vivo revealed that exercise partially reversed
      synaptic alterations that had already occurred. These results demonstrate a
      critical effect of aging on synaptic structure and provide evidence that
      interventions capable of extending health span and lifespan can partially reverse
      these age-related synaptic changes.

PMID- 20679196
TI  - Limited taste discrimination in Drosophila.
AB  - In the gustatory systems of mammals and flies, different populations of sensory
      cells recognize different taste modalities, such that there are cells that
      respond selectively to sugars and others to bitter compounds. This organization
      readily allows animals to distinguish compounds of different modalities but may
      limit the ability to distinguish compounds within one taste modality. Here, we
      developed a behavioral paradigm in Drosophila melanogaster to evaluate directly
      the tastes that a fly distinguishes. These studies reveal that flies do not
      discriminate among different sugars, or among different bitter compounds, based
      on chemical identity. Instead, flies show a limited ability to distinguish
      compounds within a modality based on intensity or palatability. Taste associative
      learning, similar to olfactory learning, requires the mushroom bodies, suggesting
      fundamental similarities in brain mechanisms underlying behavioral plasticity.
      Overall, these studies provide insight into the discriminative capacity of the
      Drosophila gustatory system and the modulation of taste behavior.

PMID- 20679197
TI  - Human milk glycobiome and its impact on the infant gastrointestinal microbiota.
AB  - Human milk contains an unexpected abundance and diversity of complex
      oligosaccharides apparently indigestible by the developing infant and instead
      targeted to its cognate gastrointestinal microbiota. Recent advances in mass
      spectrometry-based tools have provided a view of the oligosaccharide structures
      produced in milk across stages of lactation and among human mothers. One
      postulated function for these oligosaccharides is to enrich a specific "healthy"
      microbiota containing bifidobacteria, a genus commonly observed in the feces of
      breast-fed infants. Isolated culture studies indeed show selective growth of
      infant-borne bifidobacteria on milk oligosaccharides or core components therein.
      Parallel glycoprofiling documented that numerous Bifidobacterium longum subsp.
      infantis strains preferentially consume small mass oligosaccharides that are
      abundant early in the lactation cycle. Genome sequencing of numerous B. longum
      subsp. infantis strains shows a bias toward genes required to use mammalian
      derived carbohydrates by comparison with adult-borne bifidobacteria. This
      intriguing strategy of mammalian lactation to selectively nourish genetically
      compatible bacteria in infants with a complex array of free oligosaccharides
      serves as a model of how to influence the human supraorganismal system, which
      includes the gastrointestinal microbiota.

PMID- 20679198
TI  - Combining antiangiogenic therapy with immunotherapy exerts better therapeutical
      effects on large tumors in a woodchuck hepatoma model.
AB  - Cytokine and antiangiogenic gene therapies have proved effective in implanted
      hepatocellular carcinoma (HCC) models in which small tumor burdens were
      established in small rodents. These models, however, may not reflect human HCCs,
      which are frequently detected at a stage when tumors are large and multifocal. In
      addition, HCC in patients is often associated with viral hepatitis. To
      investigate the effectiveness of a mixture type of gene therapy strategy on large
      tumor burdens, we used the woodchuck model in which woodchuck hepatitis virus
      induced HCCs are large and multifocal, simulating the conditions in humans.
      Adenoviruses encoding antiangiogenic factors (pigment epithelium-derived factor
      and endostatin) or cytokines (GM-CSF and IL-12) were delivered via the hepatic
      artery separately or in combination into woodchuck livers bearing HCCs. Our
      results showed that the mixture type of strategy, which contained two cytokines
      and two antiangiogenic factors, had better antitumor effects on large tumors as
      compared with monotherapy either with antiangiogenic or cytokine genes. The
      immunotherapy recruited significant levels of CD3(+) T cells that infiltrated the
      tumors, whereas the antiangiogenesis-based therapy significantly reduced tumor
      vasculature. The mixture type of gene therapy achieved both effects. In addition,
      it induced high levels of natural killer cells and apoptotic cells and reduced
      the levels of immunosuppressive effectors in the tumor regions. Hence,
      antiangiogenic therapy may provide the advantage of reducing immune tolerance in
      large tumors, making them more vulnerable to the immune reactions. Our study
      implies that in the future, the combination therapy may prove effective for the
      treatment of patients with advanced HCC.

PMID- 20679199
TI  - eIF4E phosphorylation promotes tumorigenesis and is associated with prostate
      cancer progression.
AB  - Translational regulation plays a critical role in the control of cell growth and
      proliferation. A key player in translational control is eIF4E, the mRNA 5' cap
      binding protein. Aberrant expression of eIF4E promotes tumorigenesis and has been
      implicated in cancer development and progression. The activity of eIF4E is
      dysregulated in cancer. Regulation of eIF4E is partly achieved through
      phosphorylation. However, the physiological significance of eIF4E phosphorylation
      in mammals is not clear. Here, we show that knock-in mice expressing a
      nonphosphorylatable form of eIF4E are resistant to tumorigenesis in a prostate
      cancer model. By using a genome-wide analysis of translated mRNAs, we show that
      the phosphorylation of eIF4E is required for translational up-regulation of
      several proteins implicated in tumorigenesis. Accordingly, increased phospho
      eIF4E levels correlate with disease progression in patients with prostate cancer.
      Our findings establish eIF4E phosphorylation as a critical event in
      tumorigenesis. These findings raise the possibility that chemical compounds that
      prevent the phosphorylation of eIF4E could act as anticancer drugs.

PMID- 20679200
TI  - Predictable waves of sequential forest degradation and biodiversity loss
      spreading from an African city.
AB  - Tropical forest degradation emits carbon at a rate of approximately 0.5 Pgxy(-1),
      reduces biodiversity, and facilitates forest clearance. Understanding degradation
      drivers and patterns is therefore crucial to managing forests to mitigate climate
      change and reduce biodiversity loss. Putative patterns of degradation affecting
      forest stocks, carbon, and biodiversity have variously been described previously,
      but these have not been quantitatively assessed together or tested
      systematically. Economic theory predicts a systematic allocation of land to its
      highest use value in response to distance from centers of demand. We tested this
      theory to see if forest exploitation would expand through time and space as
      concentric waves, with each wave targeting lower value products. We used forest
      data along a transect from 10 to 220 km from Dar es Salaam (DES), Tanzania,
      collected at two points in time (1991 and 2005). Our predictions were confirmed:
      high-value logging expanded 9 kmxy(-1), and an inner wave of lower value charcoal
      production 2 kmxy(-1). This resource utilization is shown to reduce the public
      goods of carbon storage and species richness, which significantly increased with
      each kilometer from DES [carbon, 0.2 Mgxha(-1); 0.1 species per sample area (0.4
      ha)]. Our study suggests that tropical forest degradation can be modeled and
      predicted, with its attendant loss of some public goods. In sub-Saharan Africa,
      an area experiencing the highest rate of urban migration worldwide, coupled with
      a high dependence on forest-based resources, predicting the spatiotemporal
      patterns of degradation can inform policies designed to extract resources without
      unsustainably reducing carbon storage and biodiversity.

PMID- 20679201
TI  - Seasonal and interannual variability of climate and vegetation indices across the
      Amazon.
AB  - Drought exerts a strong influence on tropical forest metabolism, carbon stocks,
      and ultimately the flux of carbon to the atmosphere. Satellite-based studies have
      suggested that Amazon forests green up during droughts because of increased
      sunlight, whereas field studies have reported increased tree mortality during
      severe droughts. In an effort to reconcile these apparently conflicting findings,
      we conducted an analysis of climate data, field measurements, and improved
      satellite-based measures of forest photosynthetic activity. Wet-season
      precipitation and plant-available water (PAW) decreased over the Amazon Basin
      from 1996-2005, and photosynthetically active radiation (PAR) and air dryness
      (expressed as vapor pressure deficit, VPD) increased from 2002-2005. Using
      improved enhanced vegetation index (EVI) measurements (2000-2008), we show that
      gross primary productivity (expressed as EVI) declined with VPD and PAW in
      regions of sparse canopy cover across a wide range of environments for each year
      of the study. In densely forested areas, no climatic variable adequately
      explained the Basin-wide interannual variability of EVI. Based on a site-specific
      study, we show that monthly EVI was relatively insensitive to leaf area index
      (LAI) but correlated positively with leaf flushing and PAR measured in the field.
      These findings suggest that production of new leaves, even when unaccompanied by
      associated changes in LAI, could play an important role in Basin-wide interannual
      EVI variability. Because EVI variability was greatest in regions of lower PAW, we
      hypothesize that drought could increase EVI by synchronizing leaf flushing via
      its effects on leaf bud development.

PMID- 20679202
TI  - Synaptic input organization of the melanocortin system predicts diet-induced
      hypothalamic reactive gliosis and obesity.
AB  - The neuronal circuits involved in the regulation of feeding behavior and energy
      expenditure are soft-wired, reflecting the relative activity of the postsynaptic
      neuronal system, including the anorexigenic proopiomelanocortin (POMC)-expressing
      cells of the arcuate nucleus. We analyzed the synaptic input organization of the
      melanocortin system in lean rats that were vulnerable (DIO) or resistant (DR) to
      diet-induced obesity. We found a distinct difference in the quantitative and
      qualitative synaptology of POMC cells between DIO and DR animals, with a
      significantly greater number of inhibitory inputs in the POMC neurons in DIO rats
      compared with DR rats. When exposed to a high-fat diet (HFD), the POMC cells of
      DIO animals lost synapses, whereas those of DR rats recruited connections. In
      both DIO rats and mice, the HFD-triggered loss of synapses on POMC neurons was
      associated with increased glial ensheathment of the POMC perikarya. The altered
      synaptic organization of HFD-fed animals promoted increased POMC tone and a
      decrease in the stimulatory connections onto the neighboring neuropeptide Y (NPY)
      cells. Exposure to HFD was associated with reactive gliosis, and this affected
      the structure of the blood-brain barrier such that the POMC and NPY cell bodies
      and dendrites became less accessible to blood vessels. Taken together, these data
      suggest that consumption of an HFD has a major impact on the cytoarchitecture of
      the arcuate nucleus in vulnerable subjects, with changes that might be
      irreversible due to reactive gliosis.

PMID- 20679203
TI  - Alarm pheromone habituation in Myzus persicae has fitness consequences and causes
      extensive gene expression changes.
AB  - In most aphid species, facultative parthenogenetic reproduction allows rapid
      growth and formation of large single-genotype colonies. Upon predator attack,
      individual aphids emit an alarm pheromone to warn the colony of this danger. (E)
      beta-farnesene (EBF) is the predominant constituent of the alarm pheromone in
      Myzus persicae (green peach aphid) and many other aphid species. Continuous
      exposure to alarm pheromone in aphid colonies raised on transgenic Arabidopsis
      thaliana plants that produce EBF leads to habituation within three generations.
      Whereas naive aphids are repelled by EBF, habituated aphids show no avoidance
      response. Similarly, individual aphids from the habituated colony can revert back
      to being EBF-sensitive in three generations, indicating that this behavioral
      change is not caused by a genetic mutation. Instead, DNA microarray experiments
      comparing gene expression in naive and habituated aphids treated with EBF
      demonstrate an almost complete desensitization in the transcriptional response to
      EBF. Furthermore, EBF-habituated aphids show increased progeny production
      relative to EBF-responsive aphids, with or without EBF treatment. Although both
      naive and habituated aphids emit EBF upon damage, EBF-responsive aphids have a
      higher survival rate in the presence of a coccinellid predator (Hippodamia
      convergens), and thus outperform habituated aphids that do not show an avoidance
      response. These results provide evidence that aphid perception of conspecific
      alarm pheromone aids in predator avoidance and thereby bestows fitness benefits
      in survivorship and fecundity. Therefore, although habituated M. persicae produce
      more progeny, EBF-emitting transgenic plants may have practical applications in
      agriculture as a result of increased predation of habituated aphids.

PMID- 20679204
TI  - Profile of Gregg L. Semenza.

PMID- 20679205
TI  - A subtilisin-like protein from soybean contains an embedded, cryptic signal that
      activates defense-related genes.
AB  - Among the arsenal of plant-derived compounds activated upon attack by herbivores
      and pathogens are small peptides that initiate and amplify defense responses.
      However, only a handful of plant signaling peptides have been reported. Here, we
      have isolated a 12-aa peptide from soybean (Glycine max) leaves that causes a pH
      increase of soybean suspension-cultured cell media within 10 min at low nanomolar
      concentrations, a response that is typical of other endogenous peptide elicitors
      and pathogen-derived elicitors. The amino acid sequence was determined and was
      found to be derived from a member of the subtilisin-like protease (subtilase)
      family. The sequence of the peptide was located within a region of the protein
      that is unique to subtilases in legume plants and not found within any other
      plant subtilases thus far identified. We have named this peptide signal Glycine
      max Subtilase Peptide (GmSubPep). The gene (Glyma18g48580) was expressed in all
      actively growing tissues of the soybean plant. Although transcription of
      Glyma18g48580 was not induced by wounding, methyl jasmonate, methyl salicylate,
      or ethephon, synthetic GmSubPep peptide, when supplied to soybean cultures,
      induced the expression of known defense-related genes, such as Cyp93A1, Chib-1b,
      PDR12, and achs. GmSubPep is a unique plant defense peptide signal, cryptically
      embedded within a plant protein with an independent metabolic role, providing
      insights into plant defense mechanisms.

PMID- 20679206
TI  - A tumor-suppressing mechanism in Drosophila involving cell competition and the
      Hippo pathway.
AB  - Mutant larvae for the Drosophila gene lethal giant larva (lgl) develop neoplastic
      tumors in imaginal discs. However, lgl mutant clones do not form tumors when
      surrounded by wild-type tissue, suggesting the existence of a tumor-suppressing
      mechanism. We have investigated the tumorigenic potential of lgl mutant cells by
      generating wing compartments that are entirely mutant for lgl and also inducing
      clones of various genetic combinations of lgl(-) cells. We find that lgl(-)
      compartments can grow indefinitely but lgl(-) clones are eliminated by cell
      competition. lgl mutant cells may form tumors if they acquire constitutive
      activity of the Ras pathway (lgl(-) UAS-ras(V12)), which confers proliferation
      advantage through inhibition of the Hippo pathway. Yet, the majority of lgl(-)
      UAS-ras(V12) clones are eliminated in spite of their high proliferation rate. The
      formation of a tumor requires in addition the formation of a microenvironment
      that allows mutant cells to evade cell competition.

PMID- 20679207
TI  - Substrate-driven gene expression in Roseburia inulinivorans: importance of
      inducible enzymes in the utilization of inulin and starch.
AB  - Roseburia inulinivorans is a recently identified motile representative of the
      Firmicutes that contributes to butyrate formation from a variety of dietary
      polysaccharide substrates in the human large intestine. Microarray analysis was
      used here to investigate substrate-driven gene-expression changes in R.
      inulinivorans A2-194. A cluster of fructo-oligosaccharide/inulin utilization
      genes induced during growth on inulin included one encoding a beta
      fructofuranosidase protein that was prominent in the proteome of inulin-grown
      cells. This cluster also included a 6-phosphofructokinase and an ABC transport
      system, whereas a distinct inulin-induced 1-phosphofructokinase was linked to a
      fructose-specific phosphoenolpyruvate-dependent sugar phosphotransferase system
      (PTS II transport enzyme). Real-time PCR analysis showed that the beta
      fructofuranosidase and adjacent ABC transport protein showed greatest induction
      during growth on inulin, whereas the 1-phosphofructokinase enzyme and linked
      sugar phosphotransferase transport system were most strongly up-regulated during
      growth on fructose, indicating that these two clusters play distinct roles in the
      use of inulin. The R. inulinivorans beta-fructofuranosidase was overexpressed in
      Escherichia coli and shown to hydrolyze fructans ranging from inulin down to
      sucrose, with greatest activity on fructo-oligosaccharides. Genes induced on
      starch included the major extracellular alpha-amylase and two distinct alpha
      glucanotransferases together with a gene encoding a flagellin protein. The latter
      response may be concerned with improving bacterial access to insoluble starch
      particles.

PMID- 20679208
TI  - Metabolic adaptation for low energy throughput in orangutans.
AB  - Energy is the fundamental currency of life--needed for growth, repair, and
      reproduction--but little is known about the metabolic physiology and evolved
      energy use strategies of the great apes, our closest evolutionary relatives. Here
      we report daily energy use in free-living orangutans (Pongo spp.) and test
      whether observed differences in energy expenditure among orangutans, humans, and
      other mammals reflect known differences in life history. Using the doubly labeled
      water method, we measured daily energy expenditure (kCal/d) in orangutans living
      in a large indoor/outdoor habitat at the Great Ape Trust. Despite activity levels
      similar to orangutans in the wild, Great Ape Trust orangutans used less energy,
      relative to body mass, than nearly any eutherian mammal ever measured, including
      sedentary humans. Such an extremely low rate of energy use has not been observed
      previously in primates, but is consistent with the slow growth and low rate of
      reproduction in orangutans, and may be an evolutionary response to severe food
      shortages in their native Southeast Asian rainforests. These results hold
      important implications for the management of orangutan populations in captivity
      and in the wild, and underscore the flexibility and interdependence of
      physiological, behavioral, and life history strategies in the evolution of apes
      and humans.

PMID- 20679209
TI  - A canine Arylsulfatase G (ARSG) mutation leading to a sulfatase deficiency is
      associated with neuronal ceroid lipofuscinosis.
AB  - Neuronal ceroid lipofuscinoses (NCLs) represent the most common group of
      inherited progressive encephalopathies in children. They are characterized by
      progressive loss of vision, mental and motor deterioration, epileptic seizures,
      and premature death. Rare adult forms of NCL with late onset are known as Kufs'
      disease. Loci underlying these adult forms remain unknown due to the small number
      of patients and genetic heterogeneity. Here we confirm that a late-onset form of
      NCL recessively segregates in US and French pedigrees of American Staffordshire
      Terrier (AST) dogs. Through combined association, linkage, and haplotype
      analyses, we mapped the disease locus to a single region of canine chromosome 9.
      We eventually identified a worldwide breed-specific variant in exon 2 of the
      Arylsulfatase G (ARSG) gene, which causes a p.R99H substitution in the vicinity
      of the catalytic domain of the enzyme. In transfected cells or leukocytes from
      affected dogs, the missense change leads to a 75% decrease in sulfatase activity,
      providing a functional confirmation that the variant might be the NCL-causing
      mutation. Our results uncover a protein involved in neuronal homeostasis,
      identify a family of candidate genes to be screened in patients with Kufs'
      disease, and suggest that a deficiency in sulfatase is part of the NCL
      pathogenesis.

PMID- 20679210
TI  - Successive-signal biasing for a learned sound sequence.
AB  - Adult rats were trained to detect the occurrence of a two-element sound sequence
      in a background of nine other nontarget sound pairs. Training resulted in a
      modest, enduring, static expansion of the cortical areas of representation of
      both target stimulus sounds. More importantly, once the initial stimulus A in the
      target A-B sequence was presented, the cortical "map" changed dynamically,
      specifically to exaggerate further the representation of the "anticipated"
      stimulus B. If B occurred, it was represented over a larger cortical area by more
      strongly excited, more coordinated, and more selectively responding neurons. This
      biasing peaked at the expected time of B onset with respect to A onset. No
      dynamic biasing of responses was recorded for any sound presented in a nontarget
      pair. Responses to nontarget frequencies flanking the representation of B were
      reduced in area and in response strength only after the presentation of A at the
      expected time of B onset. This study shows that cortical areas are not
      representationally static but, to the contrary, can be biased moment by moment in
      time as a function of behavioral context.

PMID- 20679211
TI  - Requirement of open headpiece conformation for activation of leukocyte integrin
      alphaXbeta2.
AB  - Negative stain electron microscopy (EM) and adhesion assays show that
      alpha(X)beta(2) integrin activation requires headpiece opening as well as
      extension. An extension-inducing Fab to the beta(2) leg, in combination with
      representative activating and inhibitory Fabs, were examined for effect on the
      equilibrium between the open and closed headpiece conformations. The two
      activating Fabs stabilized the open headpiece conformation. Conversely, two
      different inhibitory Fabs stabilized the closed headpiece conformation. Adhesion
      assays revealed that alpha(X)beta(2) in the extended-open headpiece conformation
      had high affinity for ligand, whereas both the bent conformation and the extended
      closed headpiece conformation represented the low affinity state. Intermediate
      integrin affinity appears to result not from a single conformational state, but
      from a mixture of equilibrating conformational states.

PMID- 20679212
TI  - Prefrontal-striatal pathway underlies cognitive regulation of craving.
AB  - The ability to control craving for substances that offer immediate rewards but
      whose long-term consumption may pose serious risks lies at the root of substance
      use disorders and is critical for mental and physical health. Despite its
      importance, the neural systems supporting this ability remain unclear. Here, we
      investigated this issue using functional imaging to examine neural activity in
      cigarette smokers, the most prevalent substance-dependent population in the
      United States, as they used cognitive strategies to regulate craving for
      cigarettes and food. We found that the cognitive down-regulation of craving was
      associated with (i) activity in regions previously associated with regulating
      emotion in particular and cognitive control in general, including dorsomedial,
      dorsolateral, and ventrolateral prefrontal cortices, and (ii) decreased activity
      in regions previously associated with craving, including the ventral striatum,
      subgenual cingulate, amygdala, and ventral tegmental area. Decreases in craving
      correlated with decreases in ventral striatum activity and increases in
      dorsolateral prefrontal cortex activity, with ventral striatal activity fully
      mediating the relationship between lateral prefrontal cortex and reported
      craving. These results provide insight into the mechanisms that enable cognitive
      strategies to effectively regulate craving, suggesting that it involves neural
      dynamics parallel to those involved in regulating other emotions. In so doing,
      this study provides a methodological tool and conceptual foundation for studying
      this ability across substance using populations and developing more effective
      treatments for substance use disorders.

PMID- 20679213
TI  - Cooperation of Tim-3 and PD-1 in CD8 T-cell exhaustion during chronic viral
      infection.
AB  - Inhibitory receptors play a crucial role in regulating CD8 T-cell function during
      chronic viral infection. T-cell Ig- and mucin-domain-containing molecule-3 (Tim
      3) is well known to negatively regulate T-cell responses, but its role in CD8 T
      cell exhaustion during chronic infection in vivo remains unclear. In this study,
      we document coregulation of CD8 T cell exhaustion by Tim-3 and PD-1 during
      chronic lymphocytic choriomeningitis virus infection. Whereas Tim-3 was only
      transiently expressed by CD8 T cells after acute infection, virus-specific CD8 T
      cells retained high Tim-3 expression throughout chronic infection. The majority
      (approximately 65% to 80%) of lymphocytic choriomeningitis virus-specific CD8 T
      cells in lymphoid and nonlymphoid organs coexpressed Tim-3 and PD-1. This
      coexpression of Tim-3 and PD-1 was associated with more severe CD8 T-cell
      exhaustion in terms of proliferation and secretion of effector cytokines such as
      IFN-gamma, TNF-alpha, and IL-2. Interestingly, CD8 T cells expressing both
      inhibitory receptors also produced the suppressive cytokine IL-10. Most
      importantly, combined blockade of Tim-3 and PD-1 pathways in vivo synergistically
      improved CD8 T cell responses and viral control in chronically infected mice.
      Taken together, our study defines a parameter for determining the severity of CD8
      T cell dysfunction and for identifying virus-specific CD8 T cells that produce IL
      10, and shows that targeting both PD-1 and Tim-3 is an effective immune strategy
      for treating chronic viral infections.

PMID- 20679214
TI  - Heterodimers of NF-kappaB transcription factors DIF and Relish regulate
      antimicrobial peptide genes in Drosophila.
AB  - The innate immune response in Drosophila involves the inducible expression of
      antimicrobial peptide genes mediated by the Toll and IMD signaling pathways.
      Dorsal and DIF act downstream of Toll, whereas Relish acts downstream of IMD to
      regulate target gene expression. Dorsal, DIF, and Relish are NF-kappaB-related
      transcription factors and function as obligate dimers, but it is not clear how
      the various dimer combinations contribute to the innate immune response. We
      systematically examined the dimerization tendency of these proteins through the
      use of transgenic assays. The results show that all combinations of homo- and
      heterodimers are formed, but with varying degrees of efficiency. The formation of
      the DIF-Relish heterodimer is particularly interesting because it may mediate
      signaling for the seemingly independent Toll and IMD pathways. By incorporating a
      flexible peptide linker, we specifically tested the functions of the DIF;Relish
      (a ; sign represents the peptide linker) linked heterodimer. Our results
      demonstrate that the linked heterodimer can activate target genes of both the
      Toll and IMD pathways. The DIF and Relish complex is detectable in whole animal
      extracts, suggesting that this heterodimer may function in vivo to increase the
      spectrum and level of antimicrobial peptide production in response to different
      infections.

PMID- 20679215
TI  - Prediction of metabolic fluxes by incorporating genomic context and flux
      converging pattern analyses.
AB  - Flux balance analysis (FBA) of a genome-scale metabolic model allows calculation
      of intracellular fluxes by optimizing an objective function, such as maximization
      of cell growth, under given constraints, and has found numerous applications in
      the field of systems biology and biotechnology. Due to the underdetermined nature
      of the system, however, it has limitations such as inaccurate prediction of
      fluxes and existence of multiple solutions for an optimal objective value. Here,
      we report a strategy for accurate prediction of metabolic fluxes by FBA combined
      with systematic and condition-independent constraints that restrict the
      achievable flux ranges of grouped reactions by genomic context and flux
      converging pattern analyses. Analyses of three types of genomic contexts,
      conserved genomic neighborhood, gene fusion events, and co-occurrence of genes
      across multiple organisms, were performed to suggest a group of fluxes that are
      likely on or off simultaneously. The flux ranges of these grouped reactions were
      constrained by flux-converging pattern analysis. FBA of the Escherichia coli
      genome-scale metabolic model was carried out under several different genotypic
      (pykF, zwf, ppc, and sucA mutants) and environmental (altered carbon source)
      conditions by applying these constraints, which resulted in flux values that were
      in good agreement with the experimentally measured (13)C-based fluxes. Thus, this
      strategy will be useful for accurately predicting the intracellular fluxes of
      large metabolic networks when their experimental determination is difficult.

PMID- 20679216
TI  - Neural sensitivity to social rejection is associated with inflammatory responses
      to social stress.
AB  - Although stress-induced increases in inflammation have been implicated in several
      major disorders, including cardiovascular disease and depression, the
      neurocognitive pathways that underlie inflammatory responses to stress remain
      largely unknown. To examine these processes, we recruited 124 healthy young adult
      participants to complete a laboratory-based social stressor while markers of
      inflammatory activity were obtained from oral fluids. A subset of participants (n
      = 31) later completed an fMRI session in which their neural responses to social
      rejection were assessed. As predicted, exposure to the laboratory-based social
      stressor was associated with significant increases in two markers of inflammatory
      activity, namely a soluble receptor for tumor necrosis factor-alpha
      (sTNFalphaRII) and interleukin-6 (IL-6). In the neuroimaging subsample, greater
      increases in sTNFalphaRII (but not IL-6) were associated with greater activity in
      the dorsal anterior cingulate cortex and anterior insula, brain regions that have
      previously been associated with processing rejection-related distress and
      negative affect. These data thus elucidate a neurocognitive pathway that may be
      involved in potentiated inflammatory responses to acute social stress. As such,
      they have implications for understanding how social stressors may promote
      susceptibility to diseases with an inflammatory component.

PMID- 20679217
TI  - NADPH oxidase 2-derived reactive oxygen species in spinal cord microglia
      contribute to peripheral nerve injury-induced neuropathic pain.
AB  - Increasing evidence supports the notion that spinal cord microglia activation
      plays a causal role in the development of neuropathic pain after peripheral nerve
      injury; yet the mechanisms for microglia activation remain elusive. Here, we
      provide evidence that NADPH oxidase 2 (Nox2)-derived ROS production plays a
      critical role in nerve injury-induced spinal cord microglia activation and
      subsequent pain hypersensitivity. Nox2 expression was induced in dorsal horn
      microglia immediately after L5 spinal nerve transection (SNT). Studies using Nox2
      deficient mice show that Nox2 is required for SNT-induced ROS generation,
      microglia activation, and proinflammatory cytokine expression in the spinal cord.
      SNT-induced mechanical allodynia and thermal hyperalgesia were similarly
      attenuated in Nox2-deficient mice. In addition, reducing microglial ROS level via
      intrathecal sulforaphane administration attenuated mechanical allodynia and
      thermal hyperalgesia in SNT-injured mice. Sulforaphane also inhibited SNT-induced
      proinflammatory gene expression in microglia, and studies using primary microglia
      indicate that ROS generation is required for proinflammatory gene expression in
      microglia. These studies delineate a pathway involving nerve damage leading to
      microglial Nox2-generated ROS, resulting in the expression of proinflammatory
      cytokines that are involved in the initiation of neuropathic pain.

PMID- 20679218
TI  - A mammalian neural tissue opsin (Opsin 5) is a deep brain photoreceptor in birds.
AB  - It has been known for many decades that nonmammalian vertebrates detect light by
      deep brain photoreceptors that lie outside the retina and pineal organ to
      regulate seasonal cycle of reproduction. However, the identity of these
      photoreceptors has so far remained unclear. Here we report that Opsin 5 is a deep
      brain photoreceptive molecule in the quail brain. Expression analysis of members
      of the opsin superfamily identified as Opsin 5 (OPN5; also known as Gpr136,
      Neuropsin, PGR12, and TMEM13) mRNA in the paraventricular organ (PVO), an area
      long believed to be capable of phototransduction. Immunohistochemistry identified
      Opsin 5 in neurons that contact the cerebrospinal fluid in the PVO, as well as
      fibers extending to the external zone of the median eminence adjacent to the pars
      tuberalis of the pituitary gland, which translates photoperiodic information into
      neuroendocrine responses. Heterologous expression of Opsin 5 in Xenopus oocytes
      resulted in light-dependent activation of membrane currents, the action spectrum
      of which showed peak sensitivity (lambda(max)) at approximately 420 nm. We also
      found that short-wavelength light, i.e., between UV-B and blue light, induced
      photoperiodic responses in eye-patched, pinealectomized quail. Thus, Opsin 5
      appears to be one of the deep brain photoreceptive molecules that regulates
      seasonal reproduction in birds.

PMID- 20679219
TI  - Dispersers shape fruit diversity in Ficus (Moraceae).
AB  - Seed dispersal by vertebrates is one of the most common and important plant
      animal mutualisms, involving an enormous diversity of fruiting plants and
      frugivorous animals. Even though plant reproduction depends largely on seed
      dispersal, evolutionary ecologists have been unable to link co-occurring traits
      in fruits with differences in behavior, physiology, and morphology of fruit
      eating vertebrates. Hence, the origin and maintenance of fruit diversity remains
      largely unexplained. Using a multivariate phylogenetic comparative test with
      unbiased estimates of odor and color in figs, we demonstrate that fruit traits
      evolve in concert and as predicted by differences in the behavior, physiology
      (perceptive ability) and morphology of their frugivorous seed dispersers. The
      correlated evolution of traits results in the convergence of general appearance
      of fruits in species that share disperser types. Observations at fruiting trees
      independently confirmed that differences in fig traits predict differences in
      dispersers. Taken together, these results demonstrate that differences among
      frugivores have shaped the evolution of fruit traits. More broadly, our results
      underscore the importance of mutualisms in both generating and maintaining
      biodiversity.

PMID- 20679220
TI  - Combined deficiency for MAP kinase-interacting kinase 1 and 2 (Mnk1 and Mnk2)
      delays tumor development.
AB  - MAP kinase-interacting kinase 1 and 2 (Mnk1 and Mnk2) are protein
      serine/threonine kinases that are activated by ERK or p38 and phosphorylate
      eIF4E, which is involved in cap-dependent translation initiation. However, Mnk1/2
      double knockout (Mnk-DKO) mice show normal cell growth and development despite an
      absence of eIF4E phosphorylation. Here we show that the tumorigenesis occurring
      in the Lck-Pten mouse model (referred to here as tPten(-/-) mice) can be
      suppressed by the loss of Mnk1/2. Phosphorylation of eIF4E was greatly enhanced
      in lymphomas of parental tPten(-/-) mice compared with lymphoid tissues of wild
      type mice, but was totally absent in lymphomas of tPten(-/-); Mnk-DKO mice.
      Notably, stable knockdown of Mnk1 in the human glioma cell line U87MG resulted in
      dramatically decreased tumor formation when these cells were injected into
      athymic nude mice. Our data demonstrate an oncogenic role for Mnk1/2 in tumor
      development, and highlight these molecules as potential anticancer drug targets
      that could be inactivated with minimal side effects.

PMID- 20679221
TI  - Trimethylguanosine capping selectively promotes expression of Rev-dependent HIV-1
      RNAs.
AB  - 5'-mRNA capping is an early modification that affects pre-mRNA
      synthesis/splicing, RNA cytoplasmic transport, and mRNA translation and turnover.
      In eukaryotes, a 7-methylguanosine (m7G) cap is added to newly transcribed RNA
      polymerase II (RNAP II) transcripts. A subset of RNAP II-transcribed cellular
      RNAs, including small nuclear RNA (snRNA), small nucleolar RNA (snoRNA), and
      telomerase RNA, is further hypermethylated at the exocyclic N2 of the guanosine
      to create a trimethylguanosine (TMG)-capped RNA. Some of these TMG-capped RNAs
      are transported within the nucleus and from the nucleus to the cytoplasm by the
      CRM-1 (required for chromosome region maintenance) protein. CRM-1 is also used to
      export Rev/RRE-dependent unspliced/ partially spliced HIV-1 RNAs. Here we report
      that like snRNAs and snoRNAs, some Rev/RRE-dependent HIV-1 RNAs are TMG-capped.
      The methyltransferase responsible for TMG modification of HIV-1 RNAs is the human
      PIMT (peroxisome proliferator-activated receptor-interacting protein with
      methyltransferase) protein. TMG capping of unspliced/partially spliced HIV-1 RNAs
      represents a new regulatory mechanism for selective expression.

PMID- 20679222
TI  - Allogeneic T cells impair engraftment and hematopoiesis after stem cell
      transplantation.
AB  - Because of the perception that depleting hematopoietic grafts of T cells will
      result in poorer immune recovery and in increased risk of graft rejection, pure
      hematopoietic stem cells (HSC), which avoid the potentially lethal complication
      of graft-versus-host disease (GVHD), have not been used for allogeneic
      hematopoietic cell transplantation (HCT) in humans. Ideal grafts should contain
      HSC plus mature cells that confer only the benefits of protection from pathogens
      and suppression of malignancies. This goal requires better understanding of the
      effects of each blood cell type and its interactions during engraftment and
      immune regeneration. Here, we studied hematopoietic reconstitution post-HCT,
      comparing grafts of purified HSC with grafts supplemented with T cells in a minor
      histocompatibility antigen (mHA)-mismatched mouse model. Cell counts,
      composition, and chimerism of blood and lymphoid organs were evaluated and
      followed intensively through the first month, and then subsequently for up to 1
      yr. Throughout this period, recipients of pure HSC demonstrated superior total
      cell recovery and lymphoid reconstitution compared with recipients of T cell
      containing grafts. In the latter, rapid expansion of T cells occurred, and
      suppression of hematopoiesis derived from donor HSC was observed. Our findings
      demonstrate that even early post-HCT, T cells retard donor HSC engraftment and
      immune recovery. These observations contradict the postulation that mature donor
      T cells provide important transient immunity and facilitate HSC engraftment.

PMID- 20679223
TI  - Combinatorial homophilic interaction between gamma-protocadherin multimers
      greatly expands the molecular diversity of cell adhesion.
AB  - The specificity of interactions between neurons is believed to be mediated by
      diverse cell adhesion molecules, including members of the cadherin superfamily.
      Whereas mechanisms of classical cadherin adhesion have been studied extensively,
      much less is known about the related protocadherins (Pcdhs), which together make
      up the majority of the superfamily. Here we use quantitative cell aggregation
      assays and biochemical analyses to characterize cis and trans interactions among
      the 22-member gamma-Pcdh family, which have been shown to be critical for the
      control of synaptogenesis and neuronal survival. We show that gamma-Pcdh isoforms
      engage in trans interactions that are strictly homophilic. In contrast to
      classical cadherins, gamma-Pcdh interactions are only partially Ca(2+)-dependent,
      and their specificity is mediated through the second and third extracellular
      cadherin (EC) domains (EC2 and EC3), rather than through EC1. The gamma-Pcdhs
      also interact both covalently and noncovalently in the cis-orientation to form
      multimers both in vitro and in vivo. In contrast to gamma-Pcdh trans
      interactions, cis interactions are highly promiscuous, with no isoform
      specificity. We present data supporting a model in which gamma-Pcdh cis-tetramers
      represent the unit of their adhesive trans interactions. Unrestricted
      tetramerization in cis, coupled with strictly homophilic interactions in trans,
      predicts that the 22 gamma-Pcdhs could form 234,256 distinct adhesive interfaces.
      Given the demonstrated role of the gamma-Pcdhs in synaptogenesis, our data have
      important implications for the molecular control of neuronal specificity.

PMID- 20679224
TI  - Estrogen-dependent gallbladder carcinogenesis in LXRbeta-/- female mice.
AB  - Gallbladder cancer is a highly aggressive disease with poor prognosis that is two
      to six times more frequent in women than men. The development of gallbladder
      cancer occurs over a long time (more than 15 y) and evolves from chronic
      inflammation to dysplasia/metaplasia, carcinoma in situ, and invasive carcinoma.
      In the present study we found that, in female mice in which the oxysterol
      receptor liver X receptor-beta (LXRbeta) has been inactivated, preneoplastic
      lesions of the gallbladder developed and evolved to cancer in old animals.
      LXRbeta is a nuclear receptor involved in the control of lipid homeostasis,
      glucose metabolism, inflammation, proliferation, and CNS development. LXRbeta(-/
      ) female gallbladders were severely inflamed, with regions of dysplasia and high
      cell density, hyperchromasia, metaplasia, and adenomas. No abnormalities were
      evident in male mice, nor in LXRalpha(-/-) or LXRalpha(-/-)beta(-/-) animals of
      either sex. Interestingly, the elimination of estrogens with ovariectomy
      prevented development of preneoplastic lesions in LXRbeta(-/-) mice. The
      etiopathological mechanism seems to involve TGF-beta signaling, as the
      precancerous lesions were characterized by strong nuclear reactivity of phospho
      SMAD-2 and SMAD-4 and loss of E-cadherin expression. Upon ovariectomy, E-cadherin
      was reexpressed on the cell membranes and immunoreactivity of pSMAD-2 in the
      nuclei was reduced. These findings suggest that LXRbeta in a complex interplay
      with estrogens and TGF-beta could play a crucial role in the malignant
      transformation of the gallbladder epithelium.

PMID- 20679225
TI  - Induction and rescue of Nod2-dependent Th1-driven granulomatous inflammation of
      the ileum.
AB  - Mutations in the NOD2 gene are strong genetic risk factors for ileal Crohn's
      disease. However, the mechanism by which these mutations predispose to intestinal
      inflammation remains a subject of controversy. We report that Nod2-deficient mice
      inoculated with Helicobacter hepaticus, an opportunistic pathogenic bacterium,
      developed granulomatous inflammation of the ileum, characterized by an increased
      expression of Th1-related genes and inflammatory cytokines. The Peyer's patches
      and mesenteric lymph nodes were markedly enlarged with expansion of IFN-gamma
      producing CD4 and CD8 T cells. Rip2-deficient mice exhibited a similar phenotype,
      suggesting that Nod2 function likely depends on the Rip2 kinase in this model.
      Transferring wild-type bone marrow cells into irradiated Nod2-deficient mice did
      not rescue the phenotype. However, restoring crypt antimicrobial function of Nod2
      deficient mice by transgenic expression of alpha-defensin in Paneth cells rescued
      the Th1 inflammatory phenotype. Therefore, through the regulation of intestinal
      microbes, Nod2 function in nonhematopoietic cells of the small intestinal crypts
      is critical for protecting mice from a Th1-driven granulomatous inflammation in
      the ileum. The model may provide insight into Nod2 function relevant to
      inflammation of ileal Crohn's disease.

PMID- 20679226
TI  - Different functions of the C3HC4 zinc RING finger peroxins PEX10, PEX2, and PEX12
      in peroxisome formation and matrix protein import.
AB  - The integral peroxisomal membrane proteins PEX10, PEX2, and PEX12 contain a zinc
      RING finger close to the C terminus. Loss of function of these peroxins causes
      embryo lethality at the heart stage in Arabidopsis. Preventing the coordination
      of Zn(2+) ions by amino acid substitutions in PEX10, PEX2, and PEX12 and
      overexpressing the resulting conditional sublethal mutations in WT uncovered
      additional functions of PEX10. Plants overexpressing DeltaZn-mutant PEX10 display
      deformed peroxisomal shapes causing diminished contact with chloroplasts and
      possibly with mitochondria. These changes correlated with impaired metabolite
      transfer and, at high CO(2), recoverable defective photorespiration plus dwarfish
      phenotype. The N-terminal PEX10 domain is critical for peroxisome biogenesis and
      plant development. A point mutation in the highly conserved TLGEEY motif results
      in vermiform peroxisome shape without impairing organelle contact. Addition of an
      N-terminal T7 tag to WT PEX0 resulted in partially recoverable reduced growth and
      defective inflorescences persisting under high CO(2). In contrast, plants
      overexpressing PEX2-DeltaZn-T7 grow like WT in normal atmosphere, contain normal
      shaped peroxisomes, but display impaired peroxisomal matrix protein import. PEX12
      DeltaZn-T7 mutants exhibit unimpaired import of matrix protein and normal-shaped
      peroxisomes when grown in normal atmosphere. During seed germination, glyoxysomes
      form a reticulum around the lipid bodies for mobilization of storage oil. The
      formation of this glyoxysomal reticulum seemed to be impaired in PEX10-DeltaZn
      but not in PEX2-DeltaZn-T7 or PEX12-DeltaZn-T7 plants. Both cytosolic PEX10
      domains seem essential for peroxisome structure but differ in metabolic function,
      suggesting a role for this plant peroxin in addition to the import of matrix
      protein via ubiquitination of PEX5.

PMID- 20679227
TI  - De novo generation of white adipocytes from the myeloid lineage via mesenchymal
      intermediates is age, adipose depot, and gender specific.
AB  - It is generally assumed that white adipocytes arise from resident adipose tissue
      mesenchymal progenitor cells. We challenge this paradigm by defining a
      hematopoietic origin for both the de novo development of a subset of white
      adipocytes in adults and a previously uncharacterized adipose tissue resident
      mesenchymal progenitor population. Lineage and cytogenetic analysis revealed that
      bone marrow progenitor (BMP)-derived adipocytes and adipocyte progenitors arise
      from hematopoietic cells via the myeloid lineage in the absence of cell fusion.
      Global gene expression analysis indicated that the BMP-derived fat cells are bona
      fide adipocytes but differ from conventional white or brown adipocytes in
      decreased expression of genes involved in mitochondrial biogenesis and lipid
      oxidation, and increased inflammatory gene expression. The BMP-derived adipocytes
      accumulate with age, occur in higher numbers in visceral than in subcutaneous
      fat, and in female versus male mice. BMP-derived adipocytes may, therefore,
      account in part for adipose depot heterogeneity and detrimental changes in
      adipose metabolism and inflammation with aging and adiposity.

PMID- 20679228
TI  - CX3CR1+ CD8alpha+ dendritic cells are a steady-state population related to
      plasmacytoid dendritic cells.
AB  - Lymphoid organs are characterized by a complex network of phenotypically distinct
      dendritic cells (DC) with potentially unique roles in pathogen recognition and
      immunostimulation. Classical DC (cDC) include two major subsets distinguished in
      the mouse by the expression of CD8alpha. Here we describe a subset of CD8alpha(+)
      DC in lymphoid organs of naive mice characterized by expression of the CX(3)CR1
      chemokine receptor. CX(3)CR1(+) CD8alpha(+) DC lack hallmarks of classical
      CD8alpha(+) DC, including IL-12 secretion, the capacity to cross-present antigen,
      and their developmental dependence on the transcriptional factor BatF3. Gene
      expression profiling showed that CX(3)CR1(+) CD8alpha(+) DC resemble CD8alpha(-)
      cDC. The microarray analysis further revealed a unique plasmacytoid DC (PDC) gene
      signature of CX(3)CR1(+) CD8alpha(+) DC. A PDC relationship of the cells is
      supported further by the fact that they harbor characteristic D-J Ig gene
      rearrangements and that development of CX(3)CR1(+) CD8alpha(+) DC requires E2-2,
      the critical transcriptional regulator of PDC. Thus, CX(3)CR1(+) CD8alpha(+) DC
      represent a unique DC subset, related to but distinct from PDC. Collectively, the
      expression-profiling data of this study refine the resolution of previous DC
      definitions, sharpen the border of classical CD8alpha(+) and CD8alpha(-) DC, and
      should assist the identification of human counterparts of murine DC subsets.

PMID- 20679229
TI  - Th17 plasticity in human autoimmune arthritis is driven by the inflammatory
      environment.
AB  - In several murine models of autoimmune arthritis, Th17 cells are the dominant
      initiators of inflammation. In human arthritis the majority of IL-17-secreting
      cells within the joint express a cytokine phenotype intermediate between Th17 and
      Th1. Here we show that Th17/1 cells from the joints of children with inflammatory
      arthritis express high levels of both Th17 and Th1 lineage-specific transcription
      factors, RORC2 and T-bet. Modeling the generation of Th17/1 in vitro, we show
      that Th17 cells "convert" to Th17/1 under conditions that mimic the disease site,
      namely low TGFbeta and high IL-12 levels, whereas Th1 cells cannot convert to
      Th17. Th17/1 cells from the inflamed joint share T-cell receptor (TCR) clonality
      with Th17 cells, suggesting a shared clonal origin between Th17 and Th17/1 cells
      in arthritis. Using CD161, a lectin-like receptor that is a marker of human Th17,
      we show synovial Th17 and Th17/1 cells, and unexpectedly, a large proportion of
      Th1 cells express CD161. We provide evidence to support a Th17 origin for Th1
      cells expressing CD161. In vitro, Th17 cells that convert to a Th1 phenotype
      maintain CD161 expression. In the joint CD161+ Th1 cells share features with Th17
      cells, with shared TCR clonality, expression of RORC2 and CCR6 and response to IL
      23, although they are IL-17 negative. We propose that the Th17 phenotype may be
      unstable and that Th17 cells may convert to Th17/1 and Th1 cells in human
      arthritis. Therefore therapies targeting the induction of Th17 cells could also
      attenuate Th17/1 and Th1 effector populations within the inflamed joint.

PMID- 20679230
TI  - Impact of diet in shaping gut microbiota revealed by a comparative study in
      children from Europe and rural Africa.
AB  - Gut microbial composition depends on different dietary habits just as health
      depends on microbial metabolism, but the association of microbiota with different
      diets in human populations has not yet been shown. In this work, we compared the
      fecal microbiota of European children (EU) and that of children from a rural
      African village of Burkina Faso (BF), where the diet, high in fiber content, is
      similar to that of early human settlements at the time of the birth of
      agriculture. By using high-throughput 16S rDNA sequencing and biochemical
      analyses, we found significant differences in gut microbiota between the two
      groups. BF children showed a significant enrichment in Bacteroidetes and
      depletion in Firmicutes (P < 0.001), with a unique abundance of bacteria from the
      genus Prevotella and Xylanibacter, known to contain a set of bacterial genes for
      cellulose and xylan hydrolysis, completely lacking in the EU children. In
      addition, we found significantly more short-chain fatty acids (P < 0.001) in BF
      than in EU children. Also, Enterobacteriaceae (Shigella and Escherichia) were
      significantly underrepresented in BF than in EU children (P < 0.05). We
      hypothesize that gut microbiota coevolved with the polysaccharide-rich diet of BF
      individuals, allowing them to maximize energy intake from fibers while also
      protecting them from inflammations and noninfectious colonic diseases. This study
      investigates and compares human intestinal microbiota from children characterized
      by a modern western diet and a rural diet, indicating the importance of
      preserving this treasure of microbial diversity from ancient rural communities
      worldwide.

PMID- 20679231
TI  - Histone deacetylase inhibitor induces DNA damage, which normal but not
      transformed cells can repair.
AB  - Histone deacetylase inhibitors (HDACi) developed as anti-cancer agents have a
      high degree of selectivity for killing cancer cells. HDACi induce acetylation of
      histones and nonhistone proteins, which affect gene expression, cell cycle
      progression, cell migration, and cell death. The mechanism of the tumor selective
      action of HDACi is unclear. Here, we show that the HDACi, vorinostat
      (Suberoylanilide hydroxamic acid, SAHA), induces DNA double-strand breaks (DSBs)
      in normal (HFS) and cancer (LNCaP, A549) cells. Normal cells in contrast to
      cancer cells repair the DSBs despite continued culture with vorinostat. In
      transformed cells, phosphorylated H2AX (gammaH2AX), a marker of DNA DSBs, levels
      increased with continued culture with vorinostat, whereas in normal cells, this
      marker decreased with time. Vorinostat induced the accumulation of acetylated
      histones within 30 min, which could alter chromatin structure-exposing DNA to
      damage. After a 24-h culture of cells with vorinostat, and reculture without the
      HDACi, gammaH2AX was undetectable by 2 h in normal cells, while persisting in
      transformed cells for the duration of culture. Further, we found that vorinostat
      suppressed DNA DSB repair proteins, e.g., RAD50, MRE11, in cancer but not normal
      cells. Thus, the HDACi, vorinostat, induces DNA damage which normal but not
      cancer cells can repair. This DNA damage is associated with cancer cell death.
      These findings can explain, in part, the selectivity of vorinostat in causing
      cancer cell death at concentrations that cause little or no normal cell death.

PMID- 20679232
TI  - Direct inhibition of P/Q-type voltage-gated Ca2+ channels by Gem does not require
      a direct Gem/Cavbeta interaction.
AB  - The Rem, Rem2, Rad, and Gem/Kir (RGK) family of small GTP-binding proteins
      potently inhibits high voltage-activated (HVA) Ca(2+) channels, providing a
      powerful means of modulating neural, endocrine, and muscle functions. The
      molecular mechanisms of this inhibition are controversial and remain largely
      unclear. RGK proteins associate directly with Ca(2+) channel beta subunits
      (Ca(v)beta), and this interaction is widely thought to be essential for their
      inhibitory action. In this study, we investigate the molecular underpinnings of
      Gem inhibition of P/Q-type Ca(2+) channels. We find that a purified Gem protein
      markedly and acutely suppresses P/Q channel activity in inside-out membrane
      patches, that this action requires Ca(v)beta but not the Gem/Ca(v)beta
      interaction, and that Gem coimmunoprecipitates with the P/Q channel alpha(1)
      subunit (Ca(v)alpha(1)) in a Ca(v)beta-independent manner. By constructing
      chimeras between P/Q channels and Gem-insensitive low voltage-activated T-type
      channels, we identify a region encompassing transmembrane segments S1, S2, and S3
      in the second homologous repeat of Ca(v)alpha(1) critical for Gem inhibition.
      Exchanging this region between P/Q and T channel Ca(v)alpha(1) abolishes Gem
      inhibition of P/Q channels and confers Ca(v)beta-dependent Gem inhibition to a
      chimeric T channel that also carries the P/Q I-II loop (a cytoplasmic region of
      Ca(v)alpha(1) that binds Ca(v)beta). Our results challenge the prevailing view
      regarding the role of Ca(v)beta in RGK inhibition of high voltage-activated
      Ca(2+) channels and prompt a paradigm in which Gem directly binds and inhibits
      Ca(v)beta-primed Ca(v)alpha(1) on the plasma membrane.

PMID- 20679233
TI  - Nonmuscle myosin II isoform and domain specificity during early mouse
      development.
AB  - Nonmuscle myosins (NMs) II-A and II-B are essential for embryonic mouse
      development, but their specific roles are not completely defined. Here we examine
      the isoforms and their domain specifically in vivo and in vitro by studying mice
      and cells in which nonmuscle myosin heavy chain (NMHC) II-A is genetically
      replaced by NMHC II-B or chimeric NMHC IIs that exchange the rod and head domains
      of NM II-A and II-B. In contrast with the failure of visceral endoderm formation
      resulting in embryonic day (E)6.5 lethality of A(-)/A(-) mice, replacement with
      NM II-B or chimeric NM IIs restores a normal visceral endoderm. This finding is
      consistent with NM II's role in cell adhesion and also confirms an essential,
      isoform-independent requirement for NM II in visceral endoderm function. The
      knock-in mice die between E9.5 and 12.5 because of defects in placenta formation
      associated with abnormal angiogenesis and cell migration, revealing a unique
      function for NM II-A in placenta development. In vitro results further support a
      requirement for NM II-A in directed cell migration and focal adhesion formation.
      These findings demonstrate an isoform-specific role for NM II-A during these
      processes, making replacement by another isoform, or chimeric NM II isoforms,
      less successful. The failure of these substitutions is not only related to the
      different kinetic properties of NM II-A and II-B, but also to their subcellular
      localization determined by the C-terminal domain. These results highlight the
      functions of the N-terminal motor and C-terminal rod domains of NM II and their
      different roles in cell-cell and cell-matrix adhesion.

PMID- 20679234
TI  - Age-induced disruption of selective olfactory bulb synaptic circuits.
AB  - Little is known about how normal aging affects the brain. Recent evidence
      suggests that neuronal loss is not ubiquitous in aging neocortex. Instead, subtle
      and still controversial, region- and layer-specific alterations of neuron
      morphology and synapses are reported during aging, leading to the notion that
      discrete changes in neural circuitry may underlie age-related cognitive deficits.
      Although deficits in sensory function suggest that primary sensory cortices are
      affected by aging, our understanding of the age-related cellular and molecular
      changes is sparse. To assess the effect of aging on the organization of olfactory
      bulb (OB) circuitry, we carried out quantitative morphometric analyses in the
      mouse OB at 2, 6, 12, 18, and 24 mo. Our data establish that the volumes of the
      major OB layers do not change during aging. Parallel to this, we are unique in
      demonstrating that the stereotypic glomerular convergence of M72-GFP OSN axons in
      the OB is preserved during aging. We then provide unique evidence of the
      stability of projection neurons and interneurons subpopulations in the aging
      mouse OB, arguing against the notion of an age-dependent widespread loss of
      neurons. Finally, we show ultrastructurally a significant layer-specific loss of
      synapses; synaptic density is reduced in the glomerular layer but not the
      external plexiform layer, leading to an imbalance in OB circuitry. These results
      suggest that reduction of afferent synaptic input and local modulatory circuit
      synapses in OB glomeruli may contribute to specific age-related alterations of
      the olfactory function.

PMID- 20679235
TI  - Roles of familiarity and novelty in visual preference judgments are segregated
      across object categories.
AB  - Understanding preference decision making is a challenging problem because the
      underlying process is often implicit and dependent on context, including past
      experience. There is evidence for both familiarity and novelty as critical
      factors for preference in adults and infants. To resolve this puzzling
      contradiction, we examined the cumulative effects of visual exposure in different
      object categories, including faces, natural scenes, and geometric figures, in a
      two-alternative preference task. The results show a clear segregation of
      preference across object categories, with familiarity preference dominant in
      faces and novelty preference dominant in natural scenes. No strong bias was
      observed in geometric figures. The effects were replicated even when images were
      converted to line drawings, inverted, or presented only briefly, and also when
      spatial frequency and contour distribution were controlled. The effects of
      exposure were reset by a blank of 1 wk or 3 wk. Thus, the category-specific
      segregation of familiarity and novelty preferences is based on quick visual
      categorization and cannot be caused by the difference in low-level visual
      features between object categories. Instead, it could be due either to different
      biological significances/attractiveness criteria across these categories, or to
      some other factors, such as differences in within-category variance and adaptive
      tuning of the perceptual system.

PMID- 20679236
TI  - Differential regulation of synchronous versus asynchronous neurotransmitter
      release by the C2 domains of synaptotagmin 1.
AB  - Synaptic vesicle fusion at many synapses has been kinetically separated into two
      distinct Ca(2+)-dependent temporal components consisting of a rapid synchronous
      phase followed by a slower asynchronous component. Mutations in the synaptic
      vesicle Ca(2+) sensor Synaptotagmin 1 (Syt 1) reduce synchronous
      neurotransmission while enhancing the slower asynchronous phase of release. Syt 1
      regulation of vesicle fusion requires interactions mediated by its tandem
      cytoplasmic C2 domains (C2A and C2B). Although Ca(2+) binding by Syt 1 is
      predicted to drive synchronous release, it is unknown if Ca(2+) interactions with
      either C2 domain is required for suppression of asynchronous release. To
      determine if Ca(2+) binding by Syt 1 regulates these two phases of release
      independently, we performed electrophysiological analysis of transgenically
      expressed Syt 1 mutated at Ca(2+) binding sites in C2A or C2B in the background
      of Drosophila Syt 1-null mutants. Transgenic animals expressing mutations that
      disrupt Ca(2+) binding to C2A fully restored the synchronous phase of
      neurotransmitter release, whereas the asynchronous component was not suppressed.
      In contrast, rescue with Ca(2+)-binding mutants in C2B displayed little rescue of
      the synchronous release component, but reduced asynchronous release. These
      results suggest that the tandem C2 domains of Syt 1 play independent roles in
      neurotransmission, as Ca(2+) binding to C2A suppresses asynchronous release,
      whereas Ca(2+) binding to C2B mediates synchronous fusion.

PMID- 20679237
TI  - Compensation in the neural circuitry of fear conditioning awakens learning
      circuits in the bed nuclei of the stria terminalis.
AB  - The basolateral amygdala (BLA) is thought to be essential for fear learning.
      However, extensive training can overcome the loss of conditional fear evident
      following lesions and inactivation of the BLA. Such results suggest the existence
      of a primary BLA-dependent and a compensatory BLA-independent neural circuit. We
      tested the hypothesis that the bed nuclei of the stria terminalis (BST) provides
      this compensatory plasticity. Using extensive context-fear conditioning, we
      demonstrate that combined BLA and BST lesions prevented fear acquisition and
      expression. Additionally, protein synthesis in the BST was critical only for
      consolidation of BLA-independent but not BLA-dependent fear. Moreover, fear
      acquired after BLA lesions resulted in greater activation of BST regions that
      receive hippocampal efferents. These results suggest that the BST is capable of
      functioning as a compensatory site in the acquisition and consolidation of
      context-fear memories. Unlocking such neural compensation holds promise for
      understanding situations when brain damage impairs normal function or failure to
      regulate compensatory sites leads to anxiety disorders.

PMID- 20679238
TI  - Mnk earmarks eIF4E for cancer therapy.

PMID- 20679239
TI  - Polo-like kinase 1 phosphorylation of p150Glued facilitates nuclear envelope
      breakdown during prophase.
AB  - Nuclear envelope breakdown (NEBD) is an essential step during the G2/M transition
      in higher eukaryotic cells. Increasing evidence supports the notion that both
      microtubules and microtubule-associated motor proteins are critical regulators of
      NEBD. Although it has been described that p150(Glued), the major component of the
      dynein/dynactin complex, localizes in the nuclear envelope during prophase, the
      exact role of p150(Glued) and its regulation during NEBD are largely elusive.
      Polo-like kinase 1 (Plk1), the best characterized Ser/Thr kinase, is involved in
      mitotic entry in several systems; however, the targets of Plk1 during NEBD are
      unknown. Herein, we show that in mammalian cells both Plk1 and p150(Glued)
      regulate NEBD and that Plk1 interacts with and phosphoryates p150(Glued) during
      NEBD at prophase. Using various approaches, we showed that Plk1 phosphorylates
      p150(Glued) at Ser-179 and that the pS179 epitope is generated at the nuclear
      envelope of prophase cells. Significantly, Plk1-mediated phosphorylation of
      p150(Glued) at Ser-179 positively regulates its accumulation at the nuclear
      envelope during prophase. Finally, we found that cells expressing the Plk1
      unphosphorylatable mutant (p150(Glued)-S179A) arrest at G2, as indicated by
      reduced NEBD, increased levels of cyclin B and phospho-H3, but a decreased level
      of Cdc2 kinase activity. Taking these data together, we conclude that Plk1
      phosphorylation of p150(Glued) might be one major pathway of NEBD regulation.

PMID- 20679240
TI  - Intermolecular associations determine the dynamics of the circadian KaiABC
      oscillator.
AB  - Three proteins from cyanobacteria (KaiA, KaiB, and KaiC) can reconstitute
      circadian oscillations in vitro. At least three molecular properties oscillate
      during this reaction, namely rhythmic phosphorylation of KaiC, ATP hydrolytic
      activity of KaiC, and assembly/disassembly of intermolecular complexes among
      KaiA, KaiB, and KaiC. We found that the intermolecular associations determine key
      dynamic properties of this in vitro oscillator. For example, mutations within
      KaiB that alter the rates of binding of KaiB to KaiC also predictably modulate
      the period of the oscillator. Moreover, we show that KaiA can bind stably to
      complexes of KaiB and hyperphosphorylated KaiC. Modeling simulations indicate
      that the function of this binding of KaiA to the KaiB*KaiC complex is to
      inactivate KaiA's activity, thereby promoting the dephosphorylation phase of the
      reaction. Therefore, we report here dynamics of interaction of KaiA and KaiB with
      KaiC that determine the period and amplitude of this in vitro oscillator.

PMID- 20679241
TI  - Fluid intelligence loss linked to restricted regions of damage within frontal and
      parietal cortex.
AB  - Tests of fluid intelligence predict success in a wide range of cognitive
      activities. Much uncertainty has surrounded brain lesions producing deficits in
      these tests, with standard group comparisons delivering no clear result. Based on
      findings from functional imaging, we propose that the uncertainty of lesion data
      may arise from the specificity and complexity of the relevant neural circuit.
      Fluid intelligence tests give a characteristic pattern of activity in
      posterolateral frontal, dorsomedial frontal, and midparietal cortex. To test the
      causal role of these regions, we examined fluid intelligence in 80 patients with
      focal cortical lesions. Damage to each of the proposed regions predicted fluid
      intelligence loss, whereas damage outside these regions was not predictive. The
      results suggest that coarse group comparisons (e.g., frontal vs. posterior)
      cannot show the neural underpinnings of fluid intelligence tests. Instead,
      deficits reflect the extent of damage to a restricted but complex brain circuit
      comprising specific regions within both frontal and posterior cortex.

PMID- 20679242
TI  - Discovery of drug mode of action and drug repositioning from transcriptional
      responses.
AB  - A bottleneck in drug discovery is the identification of the molecular targets of
      a compound (mode of action, MoA) and of its off-target effects. Previous
      approaches to elucidate drug MoA include analysis of chemical structures,
      transcriptional responses following treatment, and text mining. Methods based on
      transcriptional responses require the least amount of information and can be
      quickly applied to new compounds. Available methods are inefficient and are not
      able to support network pharmacology. We developed an automatic and robust
      approach that exploits similarity in gene expression profiles following drug
      treatment, across multiple cell lines and dosages, to predict similarities in
      drug effect and MoA. We constructed a "drug network" of 1,302 nodes (drugs) and
      41,047 edges (indicating similarities between pair of drugs). We applied network
      theory, partitioning drugs into groups of densely interconnected nodes (i.e.,
      communities). These communities are significantly enriched for compounds with
      similar MoA, or acting on the same pathway, and can be used to identify the
      compound-targeted biological pathways. New compounds can be integrated into the
      network to predict their therapeutic and off-target effects. Using this network,
      we correctly predicted the MoA for nine anticancer compounds, and we were able to
      discover an unreported effect for a well-known drug. We verified an unexpected
      similarity between cyclin-dependent kinase 2 inhibitors and Topoisomerase
      inhibitors. We discovered that Fasudil (a Rho-kinase inhibitor) might be
      "repositioned" as an enhancer of cellular autophagy, potentially applicable to
      several neurodegenerative disorders. Our approach was implemented in a tool (Mode
      of Action by NeTwoRk Analysis, MANTRA, http://mantra.tigem.it).

PMID- 20679243
TI  - Interaction of JMJD6 with single-stranded RNA.
AB  - JMJD6 is a Jumonji C domain-containing hydroxylase. JMJD6 binds alpha
      ketoglutarate and iron and has been characterized as either a histone arginine
      demethylase or U2AF65 lysyl hydroxylase. Here, we describe the structures of
      JMJD6 with and without alpha-ketoglutarate, which revealed a novel substrate
      binding groove and two positively charged surfaces. The structures also contain a
      stack of aromatic residues located near the active center. The side chain of one
      residue within this stack assumed different conformations in the two structures.
      Interestingly, JMJD6 bound efficiently to single-stranded RNA, but not to single
      stranded DNA, double-stranded RNA, or double-stranded DNA. These structural
      features and truncation analysis of JMJD6 suggest that JMJD6 may bind and modify
      single-stand RNA rather than the previously reported peptide substrates.

PMID- 20679244
TI  - Nanoconjugation modulates the trafficking and mechanism of antibody induced
      receptor endocytosis.
AB  - Treatment with monoclonal antibody (mAbs) is a viable therapeutic option in
      cancer. Recently, these mAbs such as cetuximab, herceptin, etc., have been used
      as targeting agents to selectively deliver chemotherapeutics to cancerous cells.
      However, mechanisms of nanoparticles-mAbs interactions with the target cells and
      its effect on intracellular trafficking and mechanism are currently unknown. In
      this paper, we demonstrate that the distinct patterning and dynamics of anti-EGFR
      (epidermal growth factor receptor) antibody cetuximab (C225)- induced EGFR
      internalization in pancreatic cancer cells with variable receptor expression is
      altered upon nanoconjugation. Nanoconjugation uniformly enhanced C225-induced
      EGFR endocytosis in PANC-1, AsPC-1, and MiaPaca-2 cells, influenced its
      compartmentalization and regulated the involvement of dynamin-2 in the endocytic
      processes. Receptor endocytosis and its intracellular trafficking were monitored
      by confocal microscopy and transmission electron microscopy. The role of dynamin
      2 in EGFR endocytosis was determined after overexpressing either wild-type
      dynamin-2 or mutant dynamin-2 in pancreatic cancer cells followed by tracking the
      receptor-antibody complex internalization by confocal microscopy. Significantly,
      these findings demonstrate that the nanoconjugation cannot be construed as an
      innocuous reaction involved in attaching the targeting agent to the nanoparticle,
      instead it may distinctly alter the cellular processes at the molecular level, at
      least antibody induced receptor endocytosis. This information is critical for
      successful design of a nanoparticle-based targeted drug delivery system for
      future clinical translation.

PMID- 20679245
TI  - Microfluidic sorting and multimodal typing of cancer cells in self-assembled
      magnetic arrays.
AB  - We propose a unique method for cell sorting, "Ephesia," using columns of
      biofunctionalized superparamagnetic beads self-assembled in a microfluidic
      channel onto an array of magnetic traps prepared by microcontact printing. It
      combines the advantages of microfluidic cell sorting, notably the application of
      a well controlled, flow-activated interaction between cells and beads, and those
      of immunomagnetic sorting, notably the use of batch-prepared, well characterized
      antibody-bearing beads. On cell lines mixtures, we demonstrated a capture yield
      better than 94%, and the possibility to cultivate in situ the captured cells. A
      second series of experiments involved clinical samples--blood, pleural effusion,
      and fine needle aspirates--issued from healthy donors and patients with B-cell
      hematological malignant tumors (leukemia and lymphoma). The immunophenotype and
      morphology of B-lymphocytes were analyzed directly in the microfluidic chamber,
      and compared with conventional flow cytometry and visual cytology data, in a
      blind test. Immunophenotyping results using Ephesia were fully consistent with
      those obtained by flow cytometry. We obtained in situ high resolution confocal
      three-dimensional images of the cell nuclei, showing intranuclear details
      consistent with conventional cytological staining. Ephesia thus provides a
      powerful approach to cell capture and typing allowing fully automated high
      resolution and quantitative immunophenotyping and morphological analysis. It
      requires at least 10 times smaller sample volume and cell numbers than cytometry,
      potentially increasing the range of indications and the success rate of
      microbiopsy-based diagnosis, and reducing analysis time and cost.

PMID- 20679246
TI  - Evidence of Coulomb blockade behavior in a quasi-zero-dimensional quantum well on
      TiO2 surface.
AB  - Line defects on the surface of rutile TiO(2)(110) form in pairs separated by 1.2
      nm creating a quantum well. The well is effectively closed by the presence of two
      charged structures at both ends separated by a distance in the 10-20 nm range. As
      expected for quantum confinement a long period oscillatory feature of the local
      density of states is observed and attributed to the formation of discrete quantum
      states inside the system. It is at first glance surprising that the lowest energy
      quantum state of the well can be observed at room temperature. The properties of
      the quantum state cannot be explained in an independent-electron, band-like
      theory. Instead, electron-electron correlation must be included to give a
      satisfactory picture of the spatial distribution of the charge density. Theory
      predicts charging energies of 1.30 eV and 1.14 eV for quantum well lengths of 14
      nm and 16 nm, respectively, in good agreement with a classical calculation and
      the size dependence of the capacitance. This observation opens up the possibility
      of experimentally imaging the transition from a Coulomb blockade localized in a
      zero-dimensional system to an independent-particle or band-like behavior in an
      extended one-dimensional system.

PMID- 20679248
TI  - One-step acquisition of functional biomolecules from tissues.
AB  - Direct determination of functional biomolecular chemistry of clinically relevant
      tissues in vivo is a challenging task. Current approaches, based on tissue
      retrieval by biopsy and subsequent solubilization, are limited in terms of
      accurate representation of tissue constituents, reproducibility, and retention of
      functionality of solubilized tissue biomolecules. Using a pool of known
      surfactants, we designed and screened a large combinatorial library of surfactant
      formulations, which led to the discovery of rare synergistic formulations that
      greatly enhance tissue solubilization as well as preserve bioactivity of
      solubilized molecules, in particular proteins. By combining these formulations
      with a short ultrasound application, we developed a tissue sampling method--STAMP
      (Surfactant-based Tissue Acquisition for Molecular Profiling)--for rapid one-step
      determination of functional tissue chemistry in vivo. We specifically demonstrate
      STAMP-assisted profiling of a multitude of proteins, lipids, and genomic DNA in
      skin and mucosal tissues. Applications of this sampling methodology to rapid
      molecular diagnostics of cutaneous allergies and infectious diseases are also
      presented.

PMID- 20679247
TI  - Structural basis for the glucan phosphatase activity of Starch Excess4.
AB  - Living organisms utilize carbohydrates as essential energy storage molecules.
      Starch is the predominant carbohydrate storage molecule in plants while glycogen
      is utilized in animals. Starch is a water-insoluble polymer that requires the
      concerted activity of kinases and phosphatases to solubilize the outer surface of
      the glucan and mediate starch catabolism. All known plant genomes encode the
      glucan phosphatase Starch Excess4 (SEX4). SEX4 can dephosphorylate both the
      starch granule surface and soluble phosphoglucans and is necessary for processive
      starch metabolism. The physical basis for the function of SEX4 as a glucan
      phosphatase is currently unclear. Herein, we report the crystal structure of
      SEX4, containing phosphatase, carbohydrate-binding, and C-terminal domains. The
      three domains of SEX4 fold into a compact structure with extensive interdomain
      interactions. The C-terminal domain of SEX4 integrally folds into the core of the
      phosphatase domain and is essential for its stability. The phosphatase and
      carbohydrate-binding domains directly interact and position the phosphatase
      active site toward the carbohydrate-binding site in a single continuous pocket.
      Mutagenesis of the phosphatase domain residue F167, which forms the base of this
      pocket and bridges the two domains, selectively affects the ability of SEX4 to
      function as a glucan phosphatase. Together, these results reveal the unique
      tertiary architecture of SEX4 that provides the physical basis for its function
      as a glucan phosphatase.

PMID- 20679249
TI  - Amyloid beta 42 peptide (Abeta42)-lowering compounds directly bind to Abeta and
      interfere with amyloid precursor protein (APP) transmembrane dimerization.
AB  - Following ectodomain shedding by beta-secretase, successive proteolytic cleavages
      within the transmembrane sequence (TMS) of the amyloid precursor protein (APP)
      catalyzed by gamma-secretase result in the release of amyloid-beta (Abeta)
      peptides of variable length. Abeta peptides with 42 amino acids appear to be the
      key pathogenic species in Alzheimer's disease, as they are believed to initiate
      neuronal degeneration. Sulindac sulfide, which is known as a potent gamma
      secretase modulator (GSM), selectively reduces Abeta42 production in favor of
      shorter Abeta species, such as Abeta38. By studying APP-TMS dimerization we
      previously showed that an attenuated interaction similarly decreased Abeta42
      levels and concomitantly increased Abeta38 levels. However, the precise molecular
      mechanism by which GSMs modulate Abeta production is still unclear. In this
      study, using a reporter gene-based dimerization assay, we found that APP-TMS
      dimers are destabilized by sulindac sulfide and related Abeta42-lowering
      compounds in a concentration-dependent manner. By surface plasmon resonance
      analysis and NMR spectroscopy, we show that sulindac sulfide and novel sulindac
      derived compounds directly bind to the Abeta sequence. Strikingly, the attenuated
      APP-TMS interaction by GSMs correlated strongly with Abeta42-lowering activity
      and binding strength to the Abeta sequence. Molecular docking analyses suggest
      that certain GSMs bind to the GxxxG dimerization motif in the APP-TMS. We
      conclude that these GSMs decrease Abeta42 levels by modulating APP-TMS
      interactions. This effect specifically emphasizes the importance of the dimeric
      APP-TMS as a promising drug target in Alzheimer's disease.

PMID- 20679250
TI  - Telomeric repeat-containing RNA structure in living cells.
AB  - Telomeric repeat-containing RNA (referred to as TERRA), a noncoding RNA molecule,
      has recently been found in mammalian cells. The detailed structural features and
      function of the TERRA RNA at human chromosome ends remain unclear, although this
      RNA molecule may be a key component of the telomere machinery. In the present
      studies, we investigated the structural features of human TERRA RNA in living
      cells. Using a light-switching pyrene probe, we found that human TERRA RNA forms
      a parallel G-quadruplex structure in living cells, providing the in vivo evidence
      for the presence of the G-quadruplex in human TERRA RNA. Furthermore, imaging
      experiments clearly show that TERRA RNA G-quadruplex localizes to telomere DNA at
      cell nuclei. These results provide valuable information to allow understanding of
      the structure and function of human TERRA RNA.

PMID- 20679251
TI  - Deviation from the grain protein concentration-grain yield negative relationship
      is highly correlated to post-anthesis N uptake in winter wheat.
AB  - In plants, carbon and nitrogen (N) economies are intimately linked at the
      physiological and biochemical level. The strong genetic negative correlation
      between grain yield and grain protein concentration observed in various cereals
      is an illustration of this inter-relationship. Studies have shown that deviation
      from this negative relationship (grain protein deviation or GPD) has a genetic
      basis, but its physiological basis is still poorly understood. This study
      analysed data on 27 genotypes grown in multienvironment field trials,
      representing a wide range of agricultural practices and climatic conditions. The
      objective was to identify physiological processes related to the genetic
      variability in GPD. Under most environments, GPD was significantly related to
      post-anthesis N uptake independently of anthesis date and total N at anthesis.
      The underlying physiological trait might be related to genotypic differences in
      either access to soil N, regulation of N uptake by plant N status, or ability to
      maintain root activity during the grain-filling period. GPD is an interesting
      potential target in breeding as it appears to be relatively robust across
      different environments and would be valuable in increasing total N uptake by
      maturity.

PMID- 20679252
TI  - Increasing openness in oocyte donation families regarding disclosure over 15
      years.
AB  - BACKGROUND: Worldwide there is an increasing number of families created by oocyte
      donation (OD). The aim of this study was to gather information about parents'
      plans of disclosure to their child and to other people, as well as parents'
      attitudes and level of satisfaction up to 15 years after their OD treatment.
      METHODS: A questionnaire with separate material for each partner was sent to all
      parents (167 mothers, 163 fathers) who had had a child after treatment with
      donated oocytes at Vaestoliitto Fertility Clinics in Helsinki during 1992-2006.
      These parents had a total of 231 children aged 1-14 years. Parents were asked if
      they had told or intended to tell their child about his/her origin and how and
      when they had done so and about the reasons to disclose or not. Other questions
      were about openness towards other people, concerns about donor characteristics,
      counselling and feelings towards the child. RESULTS: Of the mothers, 61.1%, and
      of the fathers, 60.0%, had told or intended to tell the child of his/her
      conception. Of children over 3 years of age, 26% had already been informed. There
      was a statistically significant difference between parental telling in different
      age groups of children (P = 0.011, chi(2)). In the youngest age group (1-3
      years), 83.3% of parents were inclined to disclosure compared with 44.4% in the
      oldest age group (13-14 years). A high proportion of mothers (86.7%) and fathers
      (71.0%) had told other people about the nature of their child's conception. The
      majority of parents did not have much concern about the characteristics of the
      donor. A higher proportion of the mothers (24%) compared with fathers (11%)
      thought that the psychological support had been insufficient. They thought that
      discussions with health professionals should be arranged routinely after delivery
      or when it was time to inform the child. CONCLUSIONS: Parents with young OD
      children are clearly more inclined to disclosure compared with parents with older
      children.

PMID- 20679253
TI  - Survivin knockdown and concurrent 4-HPR treatment controlled human glioblastoma
      in vitro and in vivo.
AB  - Survivin is highly expressed in most cancers, including glioblastoma, and it
      plays a significant role in inhibiting apoptosis and promoting tumor growth.
      Treatment of cancer cells with N-(4-hydroxyphenyl) retinamide (4-HPR) induces
      apoptosis through destabilization of mitochondrial membrane and activation of
      caspase-mediated apoptotic pathways. We studied the efficacy of a combination of
      survivin knockdown and 4-HPR treatment to induce apoptosis and inhibit invasion,
      angiogenesis, and growth of human glioblastomas in vitro and in vivo. Using a
      plasmid encoding survivin shRNA, we downregulated survivin in glioblastoma U251MG
      and U118MG cells and simultaneously treated with 1 uM 4-HPR for 48 hours. Cells
      following treatments were subjected to the terminal deoxynucleotidyl transferase
      mediated dUTP nick end labeling (TUNEL) and invasion assays. In vivo angiogenesis
      and tumor regression studies were performed in nude mice. TUNEL assay
      demonstrated apoptosis in more than 80% of cells after survivin knockdown and 4
      HPR treatment. Matrigel invasion assays demonstrated marked decreases in tumor
      cell invasion. In vivo angiogenesis studies depicted a remarkable inhibition of
      neovascularization due to the knockdown of survivin and 4-HPR treatment. Imaging
      of intracerebral tumorigenesis and longitudinal studies on subcutaneous solid
      tumor formation showed dramatic decreases in tumorigenesis and solid tumor
      progression, respectively, after treatment with the combination. Studies to
      elucidate the molecular mechanisms of the inhibition of angiogenesis and tumor
      regression demonstrated marked decreases in proliferating cell nuclear antigen,
      metalloproteinase-9, vascular endothelial growth factor, basic fibroblast growth
      factor, and CD31 in solid tumors. Our data demonstrated that survivin knockdown
      and concurrent 4-HPR treatment could be a novel therapeutic strategy for
      controlling growth of human glioblastomas.

PMID- 20679254
TI  - Psychotherapy research: do we know what works for whom?
AB  - Clinical decision-making about suitability for psychological therapies is
      hampered by limitations of psychotherapy research and our lack of understanding
      of therapeutic mechanisms. Watzke et al's important randomised controlled study
      offers apparent validation for clinical judgement in relation to suitability for
      psychodynamic psychotherapy but also highlights the negative effects of
      unselected assignment to this type of treatment. Here, I consider why systematic
      selection for this form of treatment may be important and suggest how the limited
      effectiveness of psychodynamic therapy for an unselected group of patients may be
      addressed by more systematic treatment delivery and the ongoing monitoring of
      intermediate treatment outcomes.

PMID- 20679255
TI  - Recovery (2007) - psychiatry in pictures.

PMID- 20679256
TI  - A disabling combination: fatigue and depression.
AB  - Fatigue and common psychiatric symptoms - depression in particular - have
      consistently been found to be strongly associated. All have a negative impact on
      functional status, but evidence suggests that functional impairment is especially
      marked when they co-occur. Therefore, it is pertinent to understand the
      relationship between fatigue and depression.

PMID- 20679257
TI  - Ethical dilemmas: should antipsychotics ever be prescribed for people with
      dementia?
AB  - The use of antipsychotics for the treatment of behavioural and psychological
      symptoms of dementia (BPSD) is controversial. Antipsychotics cause harm and
      evidence-based guidelines advise against their use. We argue that antipsychotics
      may be justified using a palliative model: by reducing severe distress in those
      whose life expectancy is short.

PMID- 20679259
TI  - Abreaction for conversion disorder: systematic review with meta-analysis.
AB  - BACKGROUND: The value of drug interviews in the treatment of conversion disorder
      is at present unknown. AIMS: To review all the available papers published in
      English that report on the use of drug interviews for treating
      conversion/dissociative disorder. METHOD: Databases (including EMBASE, MEDLINE
      and PsycINFO) were searched from 1920 to 2009. Selected publications had to
      report on the use of drug interviews in people diagnosed with a
      conversion/dissociative disorder. Qualitative and quantitative data were
      extracted. Predictors of a positive response were ascertained using meta-analytic
      techniques. RESULTS: Fifty-five papers meeting inclusion criteria were
      identified. No studies compared the intervention with a suitable control group.
      However, two studies reported high response rates when drug interview was used in
      individuals with treatment-resistant conversion disorder. In the meta-analysis,
      the use of suggestion and occurrence of emotional catharsis during the interview
      were positively associated with recovery. Combining two medications and comorbid
      psychiatric disorder were negatively associated with recovery. CONCLUSIONS: The
      evidence for effectiveness of drug interviews is of poor quality but it may be of
      benefit in the treatment of acute and treatment-resistant conversion disorder. A
      proactive approach during the interview, making suggestions the individual will
      respond, could influence outcome. Comorbid psychiatric disorder should be treated
      conventionally. Experimental studies to determine efficacy are required.

PMID- 20679260
TI  - Effectiveness of systematic treatment selection for psychodynamic and cognitive
      behavioural therapy: randomised controlled trial in routine mental healthcare.
AB  - BACKGROUND: Although cognitive-behavioural therapy (CBT) and psychodynamic
      therapy (PDT) are both effective treatments for mental disorders, they show clear
      dissimilarities concerning their therapeutic models and treatment rationales.
      AIMS: To determine the effectiveness of systematic treatment selection (STS) to
      CBT or PDT in a mental healthcare setting compared with a control procedure of
      random treatment selection (RTS). METHOD: A randomised controlled trial in a
      consecutive sample of 291 in-patients with at least one ICD-10 mental disorder
      was performed. The primary outcome was symptom severity (General Severity Index
      of the Symptom Checklist-14) at 6-month follow-up. Health-related quality of life
      was the secondary outcome, determined using the Short Form-8. RESULTS: Analyses
      revealed no general effect for systematic treatment selection. However, there was
      a differential effect: systematic selection resulted in a better longer-term
      outcome for PDT, but not for CBT; STS-PDT patients showed a significantly larger
      reduction in symptom severity than RTS-PDT patients. This difference was not
      observed in CBT. CONCLUSIONS: Since systematic treatment selection seems to be
      able to optimise treatment outcome, at least for PDT, pursuing systematic
      treatment assignment strategies in mental healthcare settings is a worthwhile
      endeavour.

PMID- 20679261
TI  - Early child psychiatry - psychiatry in the Old Testament.

PMID- 20679262
TI  - Aetiology of fatigue in Sri Lanka and its overlap with depression.
AB  - BACKGROUND: Fatigue is a common symptom in Western high-income countries but is
      often medically unexplained and little is known about its presentation in other
      populations. AIMS: To explore the epidemiology and aetiology of fatigue in Sri
      Lanka, and of its overlap with depression. METHOD: A total of 4024 randomly
      selected twins from a population-based register in Sri Lanka (Colombo district)
      completed home interviews including the Chalder Fatigue Questionnaire. RESULTS:
      The prevalence of fatigue was similar to that in other countries, although
      prolonged fatigue may be less common. There was substantial comorbidity with a
      screen for lifetime depression. Non-shared environmental factors made the largest
      contributions, although genetic/family factors also contributed. The aetiology
      appeared consistent across the spectrum of severity. CONCLUSIONS: The aetiology
      of fatigue is broadly similar in Sri Lanka and Western high-income countries.
      Abnormal experiences of fatigue appear to be the extreme form of more common
      fatigue, rather than representing independent entities with different genetic or
      environmental risk factors.

PMID- 20679264
TI  - Burden of psychiatric disorder in young adulthood and life outcomes at age 30.
AB  - BACKGROUND: Psychiatric disorders are common during young adulthood and
      comorbidity is frequent. Individual psychiatric disorders have been shown to be
      associated with negative economic and educational outcomes, but few studies have
      addressed the relationship between the total extent of psychiatric disorder and
      life outcomes. AIMS: To examine whether the extent of common psychiatric disorder
      between ages 18 and 25 is associated with negative economic and educational
      outcomes at age 30, before and after controlling for confounding factors. METHOD:
      Participants were 987 individuals from the Christchurch Health and Development
      Study, a longitudinal study of a birth cohort of individuals born in
      Christchurch, New Zealand, in 1977 and followed to age 30. Linear and logistic
      regression models were used to examine the associations between psychiatric
      disorder from age 18 to 25 and workforce participation, income and living
      standards, and educational achievement at age 30, before and after adjustment for
      confounding factors. RESULTS: There were significant associations between the
      extent of psychiatric disorder reported between ages 18 and 25 and all of the
      outcome measures (all P<0.05). After adjustment for confounding factors, the
      associations between psychiatric disorder and workforce participation, income and
      living standards remained significant (all P<0.05), but the associations between
      psychiatric disorder and educational achievement were not significant (all
      P>0.10). CONCLUSIONS: After due allowance had been made for a range of
      confounding factors, psychiatric disorder between ages 18 and 25 was associated
      with reduced workforce participation, lower income and lower economic living
      standards at age 30.

PMID- 20679263
TI  - Associations of serious mental illness with earnings: results from the WHO World
      Mental Health surveys.
AB  - BACKGROUND: Burden-of-illness data, which are often used in setting healthcare
      policy-spending priorities, are unavailable for mental disorders in most
      countries. AIMS: To examine one central aspect of illness burden, the association
      of serious mental illness with earnings, in the World Health Organization (WHO)
      World Mental Health (WMH) Surveys. METHOD: The WMH Surveys were carried out in 10
      high-income and 9 low- and middle-income countries. The associations of personal
      earnings with serious mental illness were estimated. RESULTS: Respondents with
      serious mental illness earned on average a third less than median earnings, with
      no significant between-country differences (chi(2)(9) = 5.5-8.1, P = 0.52-0.79).
      These losses are equivalent to 0.3-0.8% of total national earnings. Reduced
      earnings among those with earnings and the increased probability of not earning
      are both important components of these associations. CONCLUSIONS: These results
      add to a growing body of evidence that mental disorders have high societal costs.
      Decisions about healthcare resource allocation should take these costs into
      consideration.

PMID- 20679265
TI  - Long-term outcomes of obsessive-compulsive disorder: follow-up of 142 children
      and adolescents.
AB  - BACKGROUND: Obsessive-compulsive disorder (OCD) often starts in childhood and
      adolescence and can be a chronic disorder with high persistence rates. There are
      few prospective long-term follow-up studies. AIMS: To follow up young people with
      OCD to clarify persistence rates and relevant predictors, presence of other
      psychiatric disorders, functional impairment, service utilisation and perceived
      treatment needs. METHOD: All young people with OCD assessed over 9 years at the
      National and Specialist Paediatric OCD clinic, Maudsley Hospital, London, were
      included. Sixty-one per cent (142 of 222) of all contactable young people and
      parents completed computerised diagnostic interviews and questionnaires. RESULTS:
      We found a persistence rate of OCD of 41%; 40% of participants had a psychiatric
      diagnosis other than OCD at follow-up. The main predictor for persistent OCD was
      duration of illness at assessment. High levels of baseline psychopathology
      predicted other psychiatric disorders at follow-up. Functional impairment and
      quality of life were mildly to moderately affected. Approximately 50% of
      participants were still receiving treatment and about 50% felt a need for further
      treatment. CONCLUSIONS: This study confirms that paediatric OCD can be a chronic
      condition that persists into adulthood. Early recognition and treatment might
      prevent chronicity. Important challenges for services are ensuring adequate
      treatment and a smooth transition from child to adult services.

PMID- 20679266
TI  - Predicting outcome in mild cognitive impairment: 4-year follow-up study.
AB  - BACKGROUND: Cognitive impairment precedes the diagnosis of Alzheimer's disease.
      It is unclear which psychometric measures predict dementia, and what cut-off
      points should be used. Replicable cognitive measures to provide information about
      differential diagnosis and prognosis would be clinically useful. AIMS: In a
      prospective cohort study we investigated which measures distinguish between
      individuals with amnestic mild cognitive impairment (aMCI) that converts to
      dementia and those whose impairment does not, and which combination of measures
      best predicts the fate of people with aMCI. METHOD: Forty-four participants with
      aMCI underwent extensive neuropsychological assessment at baseline and annually
      thereafter for an average of 4 years. Differences in baseline cognitive
      performance of participants who were converters and non-converters to clinically
      diagnosed dementia were analysed. Classification accuracy was estimated by
      sensitivity, specificity, positive and negative predictive values and using
      logistic regression. RESULTS: Forty-one percent of participants had progressed to
      dementia by the end of study, with a mean annual conversion rate of 11%. Most
      (63%) showed persisting or progressive cognitive impairment, irrespective of
      diagnosis. The Addenbrooke's Cognitive Examination together with the
      discrimination index of the Hopkins Verbal Learning Test - Revised (but none of
      the demographic indices) differentiated the participants who were converters from
      the non-converters at baseline with 74% accuracy. CONCLUSIONS: Targeted
      neuropsychological assessment, beyond simple cognitive screening, could be used
      in clinical practice to provide individuals with aMCI with prognostic information
      and aid selective early initiation of monitoring and treatment among those who
      progress towards a clinically diagnosable dementia.

PMID- 20679268
TI  - Insight, grey matter and cognitive function in first-onset psychosis.
AB  - BACKGROUND: Several studies have suggested that neuropsychological and structural
      brain deficits are implicated in poor insight. Few insight studies however have
      combined neurocognitive and structural neuroanatomical measures. AIMS: Focusing
      on the ability to relabel psychotic symptoms as pathological, we examined
      insight, brain structure and neurocognition in first-onset psychosis. METHOD:
      Voxel-based magnetic resonance imaging data were acquired from 82 individuals
      with psychosis and 91 controls assessed with a brief neuropsychological test
      battery. Insight was measured using the Schedule for the Assessment of Insight.
      RESULTS: The principal analysis showed reduced general neuropsychological
      function was linked to poor symptom relabelling ability. A subsequent between
      psychosis group analysis found those with no symptom relabelling ability had
      significant global and regional grey matter deficits primarily located at the
      posterior cingulate gyrus and right precuneus/cuneus. CONCLUSIONS: The cingulate
      gyrus (as part of a midline cortical system) along with right hemisphere regions
      may be involved in illness and symptom self-appraisal in first-onset psychosis.

PMID- 20679269
TI  - Help-seeking and receipt of treatment among UK service personnel.
AB  - BACKGROUND: For armed forces personnel, data on help-seeking behaviour and
      receipt of treatment for mental disorders are important for both research and
      policy. AIMS: To examine mental healthcare service use and receipt of treatment
      in a sample of the UK military. METHOD: Participants were drawn from an existing
      UK military health cohort. The sample was stratified by reserve status and by
      participation in the main war-fighting period of the Iraq War. Participants
      completed a telephone-based structured diagnostic interview comprising the
      Patient Health Questionnaire and Primary Care Post-Traumatic Stress Disorder
      Screen (PC-PTSD), and a series of questions about service utilisation and
      treatment receipt. RESULTS: Only 23% of those with common mental disorders and
      still serving in the military were receiving any form of medical professional
      help. Non-medical sources of help such as chaplains were more widely used. Among
      regular personnel in receipt of professional help, most were seen in primary care
      (79%) and the most common treatment was medication or counselling/psychotherapy.
      Few regular personnel were receiving cognitive-behavioural therapy (CBT). These
      findings are comparable with those reported for the general population.
      CONCLUSIONS: In the UK armed forces, the majority of those with mental disorders
      are not currently seeking medical help for their symptoms. Further work to
      understand barriers to care is important and timely given that this is a group at
      risk of occupational psychiatric injury.

PMID- 20679270
TI  - Recognition of disgusted facial expressions in severe depression.
AB  - Facial emotion processing was examined in patients with severe depression (n =
      68) and a healthy control group (n = 50), using the Facial Expression Recognition
      Task. A negative interpretation bias was observed in the depression group:
      neutral faces were more likely to be interpreted as sad and less likely to be
      interpreted as happy, compared with controls. The depression group also displayed
      a specific deficit in the recognition of facial expressions of disgust, compared
      with controls. This may relate to impaired functioning of frontostriatal
      structures, particularly the basal ganglia.

PMID- 20679271
TI  - Data and clinical utility should be the drivers of changes to psychiatric
      classification.

PMID- 20679272
TI  - Suffrage or suffering? Voting rights for psychiatric in-patients.

PMID- 20679273
TI  - Alternatives to standard acute in-patient care for people with mental disorders:
      from systematic description to evaluative research.
AB  - Many service users and professionals are not satisfied with current hospital
      care: they call for a safer and more friendly environment, with greater freedom
      and less social distance between staff and patients. Phase 2 of the Alternatives
      Study was designed to improve the evidence base for such residential
      alternatives. Findings suggest that offering a more acceptable environment
      increases satisfaction with treatment, although it does not improve the clinical
      outcome. This set of coordinated studies also suggest that we should listen (and
      talk) more to our patients, and make our style of working in hospital and
      community facilities less paternalistic.

PMID- 20679274
TI  - Alternatives to standard acute in-patient care in England: short-term clinical
      outcomes and cost-effectiveness.
AB  - BACKGROUND: Outcomes following admission to residential alternatives to standard
      in-patient mental health services are underresearched. AIMS: To explore short
      term outcomes and costs of admission to alternative and standard services.
      METHOD: Health of the Nation Outcome Scales (HoNOS), Threshold Assessment Grid
      (TAG), Global Assessment of Functioning (GAF) and admission cost data were
      collected for six alternative services and six standard services. RESULTS: All
      outcomes improved during admission for both types of service (n = 433). Adjusted
      improvement was greater for standard services in scores on HoNOS (difference
      1.99, 95% CI 1.12-2.86), TAG (difference 1.40, 95% CI 0.39-2.51) and GAF
      functioning (difference 4.15, 95% CI 1.08-7.22) but not GAF symptoms. Admissions
      to alternatives were 20.6 days shorter, and hence cheaper (UK pound3832 v.
      pound9850). Standard services cost an additional pound2939 per unit HoNOS
      improvement. CONCLUSIONS: The absence of clear-cut advantage for either type of
      service highlights the importance of the subjective experience and longer-term
      costs.

PMID- 20679275
TI  - Alternatives to standard acute in-patient care in England: readmissions, service
      use and cost after discharge.
AB  - BACKGROUND: Residential alternatives to standard psychiatric admissions are
      associated with shorter lengths of stay, but little is known about the impact on
      readmissions. AIMS: To explore readmissions, use of community mental health
      services and costs after discharge from alternative and standard services.
      METHOD: Data on use of hospital and community mental health services were
      collected from clinical records for participants in six alternative and six
      standard services for 12 months from the date of index admission. RESULTS: After
      discharge, the mean number and length of readmissions, use of community mental
      health services and costs did not differ significantly between standard and
      alternative services. Cost of index admission and total 12-month cost per
      participant were significantly higher for standard services. CONCLUSIONS: Shorter
      lengths of stay in residential alternatives are not associated with greater
      frequency or length of readmissions or greater use of community mental health
      services after discharge.

PMID- 20679276
TI  - Service users' experiences of residential alternatives to standard acute wards:
      qualitative study of similarities and differences.
AB  - BACKGROUND: Little is known about the preferences and experiences of people with
      mental illness in relation to residential alternatives to hospital. AIMS: To
      explore patients' subjective experiences of traditional hospital services and
      residential alternatives to hospital. METHOD: In-depth interviews were conducted
      with 40 purposively selected patients in residential alternative services who had
      previously experienced hospital in-patient stays. Transcripts were coded and
      analysed for thematic content. RESULTS: Patients reported an overall preference
      for residential alternatives. These were identified as treating patients with
      lower levels of disturbance, being safer, having more freedom and decreased
      coercion, and having less paternalistic staff compared with traditional in
      patient services. However, patients identified no substantial difference between
      their relationships with staff overall and the care provided between the two
      types of services. CONCLUSIONS: For patients who have acute mental illness but
      lower levels of disturbance, residential alternatives offer a preferable
      environment to traditional hospital services: they minimise coercion and maximise
      freedom, safety and opportunities for peer support.

PMID- 20679277
TI  - Effectiveness and cost-effectiveness of admissions to women's crisis houses
      compared with traditional psychiatric wards: pilot patient-preference randomised
      controlled trial.
AB  - BACKGROUND: Women's crisis houses have been developed in the UK as a less
      stigmatising and less institutional alternative to traditional psychiatric wards.
      AIMS: To examine the effectiveness and cost-effectiveness of women's crisis
      houses by first examining the feasibility of a pilot patient-preference
      randomised controlled trial (PP-RCT) design (ISRCTN20804014). METHOD: We used a
      PP-RCT study design to investigate women presenting in crisis needing informal
      admission. The four study arms were the patient preference arms of women's crisis
      house or hospital admission, and randomised arms of women's crisis house or
      hospital admission. RESULTS: Forty-one women entered the randomised arms of the
      trial (crisis house n = 19, wards n = 22) and 61 entered the patient-preference
      arms (crisis house n = 37, ward n = 24). There was no significant difference in
      outcomes (symptoms, functioning, perceived coercion, stigma, unmet needs or
      quality of life) or costs for any of the groups (randomised or preference arms),
      but women who obtained their preferred intervention were more satisfied with
      treatment. CONCLUSIONS: Although the sample sizes were too small to allow
      definite conclusions, the results suggest that when services are able to provide
      interventions preferred by patients, those patients are more likely to be
      satisfied with treatment. This pilot study provides some evidence that women's
      crisis houses are as effective as traditional psychiatric wards, and may be more
      cost-effective.

PMID- 20679278
TI  - The roots of hospital alternative care.
AB  - British hospital alternatives inherit some of their most valuable features, such
      as the use of small, domestic environments and the avoidance of coercion and
      confinement, from the early 19th-century moral management movement. The North
      American experience illustrates that these advantages can be lost if clinical
      benefits are overridden by cost and other practical concerns.

PMID- 20679279
TI  - Residential alternatives to acute in-patient care in England: satisfaction, ward
      atmosphere and service user experiences.
AB  - BACKGROUND: Alternatives to traditional in-patient services may be associated
      with a better experience of admission. AIMS: To compare patient satisfaction,
      ward atmosphere and perceived coercion in the two types of service, using
      validated measures. METHOD: The experience of 314 patients in four residential
      alternatives and four standard services were compared using the Client
      Satisfaction Questionnaire (CSQ), the Service Satisfaction Scale - Residential
      form (SSS-Res), the Ward Atmosphere Scale (WAS) and the Admission Experience
      Scale (AES). RESULTS: Compared with standard wards, service users from
      alternative services reported greater levels of satisfaction (mean difference CSQ
      3.3, 95% CI 1.8 to 4.9; SSS-Res 11.4, 95% CI 5.0 to 17.7). On the AES, service
      users in alternatives perceived less coercion (mean difference -1.3, 95% CI -1.8
      to -0.8) and having more ;voice' (mean difference 0.9, 95% CI 0.6 to 1.2).
      Greater autonomy, more support and less anger and aggression were revealed by WAS
      scores. Differences in CSQ and AES scores remained significant after
      multivariable adjustment, but SSS-Res results were attenuated, mainly by
      detention status. CONCLUSIONS: Community alternatives were associated with
      greater service user satisfaction and less negative experiences. Some but not all
      of these differences were explained by differences in the two populations,
      particularly in involuntary admission.

PMID- 20679280
TI  - Alternatives to standard acute in-patient care in England: differences in content
      of care and staff-patient contact.
AB  - BACKGROUND: Differences in the content of care provided by acute in-patient
      mental health wards and residential crisis services such as crisis houses have
      not been researched. AIMS: To compare planned and actual care provided at
      alternative and standard acute wards and to investigate the relationship between
      care received and patient satisfaction. METHOD: Perspectives of stakeholders,
      including local service managers, clinicians and commissioners, were obtained
      from 23 qualitative interviews. Quantitative investigation of the care provided
      at four alternative and four standard services was undertaken using three
      instruments developed for this study. The relationship of care received to
      patient satisfaction was explored. RESULTS: No significant difference was found
      in intensity of staff-patient contact between alternative and standard services.
      Alternative services provided more psychological and less physical and
      pharmacological care than standard wards. Care provision may be more
      collaborative and informal in alternative services. All measured types of care
      were positively associated with patient satisfaction. Measured differences in the
      care provided did not explain the greater acceptability of community
      alternatives. CONCLUSIONS: Similarities in care may be more marked than
      differences at alternative and standard services. Staff-patient contact is an
      important determinant of patient satisfaction, so increasing it should be a
      priority for all acute in-patient services.

PMID- 20679281
TI  - Where next with residential alternatives to admission?
AB  - The quest for alternatives to traditional psychiatric wards has a long history
      but methodological difficulties have limited research into their benefits. Two UK
      studies suggest that community-based residential alternatives are valued by
      service users and may be cost-effective. Establishing and/or maintaining such
      services, where they function as an integrated component of local acute care
      pathways, is a justifiable decision. However, our findings do not provide
      compelling evidence that they should be seen as essential in every catchment
      area. Quality of therapeutic relationships appears central to service user
      experiences, and future research should explore how this may be improved in both
      hospital and community settings.

PMID- 20679282
TI  - Alternatives to standard acute in-patient care in England: roles and populations
      served.
AB  - BACKGROUND: Key questions regarding residential alternatives to standard acute
      psychiatric care, such as crisis houses and short-stay in-patient units, concern
      the role that they fulfil within local acute care systems, and whether they
      manage people with needs and illnesses of comparable severity to those admitted
      to standard acute wards. AIMS: To study the extent to which people admitted to
      residential alternatives and to standard acute services are similar, and the role
      within local acute care systems of admission to an alternative service. METHOD:
      Our approach combined quantitative and qualitative methods. Consecutive cohorts
      of patients in six residential alternatives across England and six standard acute
      wards in the same areas were identified, and clinical and demographic
      characteristics, severity of symptoms, impairments and risks compared. Semi
      structured interviews with key stakeholders in each local service system were
      used to explore the role and functioning of each alternative. RESULTS: Being
      already known to services (OR = 2.6, 95% CI 1.3-5.2), posing a lower risk to
      others (OR = 0.49, 95% CI 0.31-0.78) and having initiated help-seeking in the
      current crisis (OR = 2.2, 95% CI 1.2-4.3) were associated with being admitted to
      an alternative rather than a standard service. Stakeholder interviews suggested
      that alternatives have a role that is similar but not identical to standard
      hospital services. They can divert some, but not all, patients from acute
      admission. CONCLUSIONS: Residential alternatives are integrated into catchment
      area mental health systems. They serve similar, but not identical, clinical
      populations to standard acute wards and provide some, but not all, of the
      functions of these wards.

PMID- 20679283
TI  - Parvovirus B19 and C-reactive protein in blood bank donors: implications for
      hygiene hypothesis research.
AB  - Exposure to certain environmental factors during childhood may influence the
      developing immune system, causing predisposing or protective effects toward
      development of autoimmune disorders. This study examines the hypothesis that past
      infection with parvovirus B19, a common childhood infection, is associated with
      altered levels of subclinical inflammatory activity in presumably healthy adults.
      Qualitative anti-parvovirus B19 IgG antibody and high-sensitivity C-reactive
      protein were determined in serum samples from adult blood bank donors. C-reactive
      protein values of B19 IgG-positive and B19 IgG-negative groups were compared.
      Analysis was performed on 282 blood bank donor serum samples. Among donors aged
      17-49 years (n = 152), B19 IgG-positive samples (57.9%) were associated with
      significantly lower C-reactive protein levels compared with B19 IgG-negative
      samples (median C-reactive protein: 1.30 mg/l vs. 2.65 mg/l; p = 0.012 unadjusted
      (Mann-Whitney U-test); p = 0.014 adjusted for gender and age (logistic
      regression)). Among donors aged >49 years, median C-reactive protein levels were
      identical by B19 IgG status. The association of B19 IgG antibody with lower C
      reactive protein levels in the serum of younger adults supports the hypothesis
      that infection in childhood may contribute long-term beneficial adaptive immune
      responses.

PMID- 20679284
TI  - Analysis of threshold-type behaviour in mathematical models of the intrusion of a
      novel macroparasite in a host colony.
AB  - Macroparasites include worms, ticks, mites, bugs and fleas. These parasites are
      well known to induce morbidity effects including a reduction in the hosts'
      reproductive output and survival. An important scenario is the introduction of a
      new macroparasite into an established host population which may be caused by the
      climate change and by the transport of domestic animals. The aim of the article
      is to demonstrate an interesting feature of this scenario using a mathematical
      model with four dimensionless parameters. Six possible scenarios of introducing a
      new macroparasite into a host colony, ranging from the elimination of the new
      pathogen, through guaranteed host and parasite coexistence, to the collapse of
      the host colony are distinguished. The threshold surfaces in the space of
      parameters which separate the different scenarios are found. Some special limit
      cases are discussed.

PMID- 20679285
TI  - Media coverage and public reaction to a celebrity cancer diagnosis.
AB  - BACKGROUND: Celebrity diagnoses can have important effects on public behaviour.
      UK television celebrity Jade Goody died from cervical cancer in 2009. We
      investigated the impact of her illness on media coverage of cervical cancer
      prevention, health information seeking behaviour and cervical screening coverage.
      METHODS: National UK newspaper articles containing the words 'Jade Goody' and
      'cancer' were examined for public health messages. Google Insights for Search was
      used to quantify Internet searches as a measure of public health information
      seeking. Cervical screening coverage data were examined for temporal associations
      with this story. RESULTS: Of 1203 articles, 116 (9.6%) included a clear public
      health message. The majority highlighted screening (8.2%). Fewer articles
      provided advice about vaccination (3.0%), number of sexual partners (1.4%),
      smoking (0.6%) and condom use (0.4%). Key events were associated with increased
      Internet searches for 'cervical cancer' and 'smear test', although only weakly
      with searches for 'HPV'. Cervical screening coverage increased during this
      period. CONCLUSION: Increased public interest in disease prevention can follow a
      celebrity diagnosis. Although media coverage sometimes included public health
      information, articles typically focused on secondary instead of primary
      prevention. There is further potential to maximize the public health benefit of
      future celebrity diagnoses.

PMID- 20679286
TI  - Managing the production of a Cochrane systematic review.

PMID- 20679287
TI  - Editorial 25:4: It's all in the ratios.

PMID- 20679290
TI  - Pre-clinical laboratory evaluation of the new 'AF' arterial line filter range.
AB  - INTRODUCTION: The presence of emboli was recognised relatively early in the
      history of open heart surgery. The emboli produced during cardiopulmonary bypass
      have the predisposition to distribute into, and ultimately obstruct, microvessels
      of all tissues. The Sorin Group has recently developed a new range of arterial
      line filters. Before the Sorin AF range of filters was released for pre-launch
      clinical trials, our group performed in vitro laboratory testing of the AF range
      against a selection of commercially available filters on the global market.
      RESULTS: The Sorin AF620 and AF640 demonstrate both the smallest prime volume and
      smallest surface contact area (92ml and 290 cm(2), respectively).The results of
      the GME Handling Efficiency experiments ranged by 39.6%, from 95.9% to 56.3%. In
      terms of an air bolus handling, the results of the Limit Bolus experiment ranged
      by 97 ml, from 147.5 ml down to 50 ml. The pressure drop across all the filters
      was measured under steady state experimental conditions. All of the above
      investigations were considered against surface area and prime volume. CONCLUSION:
      It is clear from the results that some commercially available arterial line
      filters perform better than others, not only in overall performance, but also
      with regard to individual characteristics. Evaluating arterial line filters for
      hospital-specific use has to balance pressure drop, surface area, micro air
      handling, prime volume and gross air handling; all points need to be considered.
      In the AF620 and AF640, Sorin boast that they are the two smallest prime and
      smallest surface area filters commercially available on the global market. The
      Sorin AF filter range performs well in all of the areas we investigated and will
      be a competitive option for centres, irrespective of which characteristics they
      use to evaluate and select their arterial line filter.

PMID- 20679294
TI  - Former director of mental health trust is struck off for unacceptable behaviour.

PMID- 20679291
TI  - The vegetative state.

PMID- 20679295
TI  - CDX2 in congenital gut gastric-type heteroplasia and intestinal-type Meckel
      diverticula.
AB  - The mechanisms that determine organ identity along the digestive tract in humans
      are poorly understood. Here we describe the rare case of a young patient who
      presented with congenital gastric-type heteroplasia in the midjejunum. The
      lesions, located along the antimesenteric midline of the gut, were made of
      histologically and functionally normal gastric epithelium without inflammation or
      in situ/invasive carcinoma. They resembled the anatomy of the lesions developing
      in the mouse gut as a result of haploinsufficiency of the Cdx2 homeobox gene. The
      lesions were devoid of CDX2 but without mutation in the coding sequence or in a
      cis-regulatory element required for intestine-specific expression. Combining
      these data with the CDX2 expression pattern established from human embryos and
      cases of Meckel diverticula, we propose a scenario for this patient's
      presentation, in which CDX2 was missing at the site of ventral closure during gut
      morphogenesis, with subsequent default differentiation into gastric instead of
      intestinal tissue. Altogether, these observations argue in favor of a pivotal
      role played by CDX2 in determining intestinal identity during human embryonic
      development, as previously shown experimentally in mice.

PMID- 20679297
TI  - Acute, reversible axonal energy failure during stroke-like episodes in MELAS.
AB  - The pathophysiology of stroke-like episodes in MELAS (mitochondrial myopathy,
      encephalopathy, lactic acidosis, and stroke-like episodes) remains unresolved.
      Possible mechanisms include mitochondrial angiopathy, cytopathy, or both,
      collectively resulting in cellular energy depletion. To clarify disease
      mechanisms, axonal excitability properties were investigated in a 10-year-old
      child with MELAS. Serial assessments during a stroke-like episode revealed
      reversible depolarization of the axonal membrane consistent with disruption of
      energy-dependent processes. Axonal parameters correlated with the clinical
      assessment of central dysfunction and biochemical measures of acidosis. Novel
      axonal excitability techniques have established acute, reversible ischemic-like
      depolarization that may serve as a surrogate marker of central events that
      develop during stroke-like episodes in MELAS.

PMID- 20679296
TI  - Early medical and behavioral characteristics of NICU infants later classified
      with ASD.
AB  - OBJECTIVES: Recent evidence suggests higher prevalence of autism spectrum
      disorder (ASD) in NICU graduates. This aim of this study was to identify
      retrospectively early behaviors found more frequently in NICU infants who went on
      to develop ASD. METHODS: Twenty-eight NICU graduates who later received a
      diagnosis of ASD were compared with 2169 other NICU graduates recruited from 1994
      to 2005. They differed in gender, gestational age, and birth cohort. These
      characteristics were used to draw a matched control sample (n=112) to determine
      which, if any, early behaviors discriminated subsequent ASD diagnosis. Behavioral
      testing at targeted ages (adjusted for gestation) included the Rapid Neonatal
      Neurobehavioral Assessment (hospital discharge, 1 month), Arousal-Modulated
      Attention (hospital discharge, 1 and 4 months), and Bayley Scales of Infant
      Development (multiple times, 4-25 months). RESULTS: At 1 month, children with ASD
      but not control children had persistent neurobehavioral abnormalities and higher
      incidences of asymmetric visual tracking and arm tone deficits. At 4 months,
      children with ASD had continued visual preference for higher amounts of
      stimulation than did control children, behaving more like newborns. Unlike
      control children, children with ASD had declining mental and motor performance by
      7 to 10 months, resembling infants with severe central nervous system
      involvement. CONCLUSIONS: Differences in specific behavior domains between NICU
      graduates who later receive a diagnosis of ASD and matched NICU control children
      may be identified in early infancy. Studies with this cohort may provide insights
      to help understand and detect early disabilities, including ASD.

PMID- 20679298
TI  - Household cleaning product-related injuries treated in US emergency departments
      in 1990-2006.
AB  - OBJECTIVE: The goal was to examine comprehensively the patterns and trends of
      household cleaning product-related injuries among children treated in US
      emergency departments. METHODS: Through use of the National Electronic Injury
      Surveillance System database, cases of unintentional, nonfatal, household
      cleaning product-related injuries were selected by using product codes for drain
      cleaners, ammonia, metal polishes/tarnish removers, turpentine, dishwasher
      detergents, acids, swimming pool chemicals, oven cleaners, pine oil
      cleaners/disinfectants, laundry soaps/detergents, toilet bowl products, abrasive
      cleaners, general-purpose household cleaners, noncosmetic bleaches, windshield
      wiper fluids, caustic agents, lye, wallpaper cleaners, room
      deodorizers/fresheners, spot removers, and dishwashing liquids. Products were
      categorized according to major toxic ingredients, mode of action, and exposure.
      RESULTS: An estimated 267 269 children<or=5 years of age were treated in US
      emergency departments for household cleaning product-related injuries. The number
      of injuries attributable to household cleaning product exposure decreased 46.0%
      from 22 141 in 1990 to 11 964 in 2006. The product most-commonly associated with
      injury was bleach (37.1%). Children 1 to 3 years of age accounted for 72.0% of
      cases. The primary mechanism of injury was ingestion (62.7%). The most common
      source or container was spray-bottles (40.1%). Although rates of household
      cleaner-related injuries from regular bottles or original containers and
      kitchenware decreased during the study period, spray-bottle injury rates showed
      no decrease. CONCLUSION: Although national rates of household cleaning product
      related injuries in children decreased significantly over time, the number of
      injuries remains high.

PMID- 20679299
TI  - Knowledge on pulse oximetry among pediatric health care professionals: a
      multicenter survey.
AB  - OBJECTIVES: The objective of this study was to assess the knowledge on pulse
      oximetry among health care professionals involved in pediatric care. METHODS: A
      multiple-choice questionnaire was distributed to 505 pediatric health care
      professionals from 19 hospitals and health centers throughout Greece. Exploratory
      factor analysis was performed to identify underlying factors that could explain
      most of the variance of the responses. The mean test and factor scores were
      calculated and compared between clinical settings. RESULTS: The mean test score
      was 61.9+/-18.1%. After factor analysis, 2 distinct groups of deficits in
      knowledge regarding pulse oximetry were identified: 1 was interpreted as relating
      to practical knowledge and the other to theoretical knowledge. The mean score of
      the items that assessed practical knowledge was 82.7+/-12.5% and of those that
      assessed theoretical knowledge was 44.2+/-21.7%. Pediatricians and family
      practitioners, participants from level 3 institutions, and health care
      professionals working in ICUs scored better, particularly on the items that
      assessed theoretical knowledge. Logistic regression analysis revealed that only
      participants from level 3 institutions and those from ICUs had a greater
      likelihood of achieving a higher score (total score odds ratio: level 3, 2.89,
      ICU, 8.13; theoretical knowledge odds ratio: level 3, 3.40, ICU, 10.95).
      CONCLUSIONS: Pediatric health care professionals have marked deficiencies in
      their knowledge on pulse oximetry, particularly in regard to the principles
      underlying the method and its limitations. Strategies that are directed at
      improving knowledge on pulse oximetry are urgently needed at all levels of
      experience in pediatric care.

PMID- 20679300
TI  - DMSA scan for revealing vesicoureteral reflux in young children with urinary
      tract infection.
AB  - OBJECTIVES: The objective of this study was to assess the ability of acute
      dimercaptosuccinic acid (DMSA) scintigraphy for revealing vesicoureteral reflux
      (VUR) in young children after a first febrile urinary tract infection (UTI).
      METHODS: Children aged<or=24 months and were admitted with a first febrile UTI
      during a 5-year period were evaluated. The ability of acute DMSA scintigraphy to
      reveal dilating (grades 3-5) or severe (grades 4-5) VUR was assessed by comparing
      DMSA scan findings with those of voiding cystourethrography. RESULTS: Of the 296
      children included, 46 had dilating and 25 severe VUR. Abnormal DMSA scan results
      were associated with an odds ratio of 4.36 for dilating and 5.50 for severe VUR.
      For detecting dilating VUR, the area under the curve (AUC) was 0.68, the positive
      likelihood ratio (LR) was 2.00, and the negative LR was 0.46; for severe VUR,
      those values were 0.69, 2.10, and 0.38, respectively. Children with abnormal DMSA
      scan results combined with abnormal ultrasonography had an odds ratio of 3.60 for
      dilating and 6.32 for severe VUR. Despite normal findings on both investigations,
      12 children had dilating and 4 severe VUR. For dilating VUR, the area under the
      (AUC) was 0.65, the positive LR was 1.70, and the negative LR was 0.47; for
      severe VUR, the values were 0.69, 1.90, and 0.29, respectively. CONCLUSIONS: Our
      data suggest that acute DMSA scintigraphy has limited overall ability in
      identifying VUR and should not be endorsed as replacement for voiding
      cystourethrography in the evaluation of young children with a first febrile UTI.

PMID- 20679301
TI  - International variations in harsh child discipline.
AB  - BACKGROUND: Although the history of recognition of child abuse in Europe and
      North America extends over 40 years, recognition and data are lacking in other
      parts of the world. Cultural differences in child-rearing complicate cross
      cultural studies of abuse. OBJECTIVE: To ascertain rates of harsh and less-harsh
      parenting behavior in population-based samples. METHODS: We used parallel surveys
      of parental discipline of children in samples of mothers in Brazil, Chile, Egypt,
      India, Philippines, and the United States. Data were collected between 1998 and
      2003. The instrument used was a modification of the Parent-Child Conflict Tactics
      Scale, along with a study-developed survey of demographic characteristics and
      other parent and child variables. Women (N=14 239) from 19 communities in 6
      countries were surveyed. We interviewed mothers aged 15 to 49 years (18-49 years
      in the United States) who had a child younger than 18 years in her home. Sample
      selection involved either random sampling or systematic sampling within randomly
      selected blocks or neighborhoods. RESULTS: Nearly all parents used nonviolent
      discipline and verbal or psychological punishment. Physical punishment was used
      in at least 55% of the families. Spanking rates (with open hand on buttocks)
      ranged from a low of 15% in an educated community in India to a high of 76% in a
      Philippine community. Similarly, there was a wide range in the rates of children
      who were hit with objects (9%-74% [median: 39%]) or beaten by their parents (0.1%
      28.5%). Extremely harsh methods of physical punishment, such as burning or
      smothering, were rare in all countries. It is concerning that >or=20% of parents
      in 9 communities admitted shaking children younger than 2 years. CONCLUSIONS:
      Physical and verbal punishments of children are common in high-, middle-, and low
      income communities around the world. The forms and rates of punishment vary among
      countries and among communities within countries. A median of 16% of children
      experienced harsh or potentially abusive physical discipline in the previous
      year.

PMID- 20679302
TI  - Influence of peers on breastfeeding discontinuation among new parents: the
      Melbourne InFANT Program.
AB  - OBJECTIVE: We aimed to investigate whether the proportion of breastfeeding
      mothers in first-time parent groups influenced the likelihood of ceasing
      breastfeeding and whether this was independent of socioeconomic position.
      METHODS: Data were from 501 mothers (from 62 first-time parent groups initiated
      approximately 6 weeks after birth) who provided data at the baseline and mid
      intervention assessments of the Melbourne Infant Feeding, Activity, and Nutrition
      Trial. Parent groups were divided into those in which <or=25% of mothers had
      ceased breastfeeding by 6 weeks (low-cessation groups) and those in which >25%
      had ceased by 6 weeks (high-cessation groups). RESULTS: With the exclusion of
      mothers who had already ceased breastfeeding by 6 weeks, the proportion of
      mothers who ceased breastfeeding between the time of parent group initiation (6
      weeks) and 6 months was higher in high-cessation groups than in low-cessation
      groups (37.4% vs 21.7%; P=.001). After adjustment for maternal age, BMI,
      employment, and education and area-level socioeconomic position, membership in a
      group in which a large proportion of mothers had ceased breastfeeding by 6 weeks
      was strongly related to cessation of breastfeeding before 6 months (odds ratio:
      2.1 [95% confidence interval: 1.3-3.3]). CONCLUSIONS: Attendance at parent groups
      where peers are breastfeeding infants of a similar age may have an important
      influence on the continuation of breastfeeding to 6 months. First-time parent
      groups or other similar groups may be an important setting in which to promote
      the continuation of breastfeeding.

PMID- 20679303
TI  - Cardiac findings in congenital muscular dystrophies.
AB  - Cardiac involvement (CI) in congenital muscular dystrophies (CMDs) has been only
      rarely investigated so far. By means of a systematic literature search we
      reviewed the literature about CI in CMD and found that CI is apparently absent in
      Ullrich CMD or CMD with integrin deficiency and only mild in Bethlem CMD. CI in
      merosin deficiency includes dilated cardiomyopathy and systolic dysfunction. CI
      in dystroglycanopathies seems most prevalent among all CMDs and includes dilated
      cardiomyopathy, systolic dysfunction, and myocardial fibrosis in Fukuyama CMD.
      Among the nonspecified dystroglycanopathies, CI manifests as dilated
      cardiomyopathy, hypertrophic cardiomyopathy (CMP) or systolic dysfunction. With
      CMD type 1C, as well as with limb-girdle muscular dystrophy 2I, up to half of the
      patients develop dilated cardiomyopathy. In rigid-spine syndrome, predominantly
      the right heart is affected secondary to thoracic deformity. In patients who
      carry LMNA mutations, CI may manifest as dilated cardiomyopathy, hypertrophic
      cardiomyopathy, or fatal ventricular arrhythmias. Overall, CI in patients with
      CMD varies considerably between the different CMD types from absent or mild CI to
      severe cardiac disease, particularly in merosin deficiency, dystroglycanopathies,
      and laminopathies. Patients with CMD with CI require regular cardiologic
      surveillance so that severe, treatable cardiac disease is not overlooked.

PMID- 20679304
TI  - Respiratory arrest from Ascaris lumbricoides.
AB  - We report here the successful treatment of a 9-year-old boy who suffered a high
      voltage electrical injury and a hospital course complicated by unexpected airway
      obstruction from Ascaris lumbricoides. Review of the literature revealed 4
      previous reports of this complication. We also discuss options for prevention and
      treatment of this rare complication of a common infestation.

PMID- 20679305
TI  - Deodorant spray: a newly identified cause of cold burn.
AB  - Two patients encountered a first-degree cold burn after use of a deodorant spray.
      The spray-nozzle to skin-surface distance was approximately 5 cm, and the
      spraying lasted approximately 15 seconds. Under laboratory conditions, the
      deodorant in use was able to induce a decline in temperature of >60 degrees C.
      These 2 cases highlight a little-known potential for skin damage by deodorant
      sprays if used improperly.

PMID- 20679307
TI  - Reducing childhood mortality from diarrhea and lower respiratory tract infections
      in Brazil.
AB  - OBJECTIVE: To evaluate the effects of the Family Health Program (FHP), a strategy
      for reorganization of primary health care in Brazil, on mortality of children
      younger than 5 years, particularly from diarrheal diseases and lower respiratory
      tract infections. METHODS: Mortality rates and the extent of FHP coverage from
      2000 to 2005 was evaluated from the 2601 (of 5507) Brazilian municipalities with
      an adequate quality of vital information. A multivariable regression analysis for
      panel data was conducted by using a negative binomial model with fixed effects,
      adjusted for relevant demographic and socioeconomic covariates. RESULTS: A
      statistically significant negative association was observed between FHP coverage
      levels, classified as none (the reference category), low (<30%), intermediate
      (>or=30% and <70%), or high (>or=70%), and all analyzed mortality rates, with a
      reduction of 4% (95% confidence interval [CI]: 2%-6%), 9% (95% CI: 7%-12%), and
      13% (95% CI: 10%-15%), respectively, on mortality rates or children younger than
      5. The greatest effect was on postneonatal mortality. Reductions of 31% (95% CI:
      20%-40%) and 19% (95% CI: 8%-28%) in mortality rates from diarrheal diseases and
      lower respiratory infections, respectively, were found in the group of
      municipalities with the highest FHP coverage. CONCLUSIONS: The FHP, one of the
      largest comprehensive primary health care programs in the world, was effective in
      reducing overall mortality of children younger than 5, and particularly deaths
      related to diarrheal diseases and lower respiratory tract infections.

PMID- 20679306
TI  - Human papillomavirus vaccination practices: a survey of US physicians 18 months
      after licensure.
AB  - OBJECTIVES: The objectives of this study were to assess, in a nationally
      representative network of pediatricians and family physicians, (1) human
      papillomavirus (HPV) vaccination practices, (2) perceived barriers to
      vaccination, and (3) factors associated with whether physicians strongly
      recommended HPV vaccine to 11- to 12-year-old female patients. METHODS: In
      January through March 2008, a survey was administered to 429 pediatricians and
      419 family physicians. RESULTS: Response rates were 81% for pediatricians and 79%
      for family physicians. Ninety-eight percent of pediatricians and 88% of family
      physicians were administering HPV vaccine in their offices (P<.001). Among those
      physicians, fewer strongly recommended HPV vaccination for 11- to 12-year-old
      female patients than for older female patients (pediatricians: 57% for 11- to 12
      year-old patients and 90% for 13- to 15-year-old patients; P<.001; family
      physicians: 50% and 86%, respectively; P<.001). The most-frequently reported
      barriers to HPV vaccination were financial, including vaccine costs and insurance
      coverage. Factors associated with not strongly recommending HPV vaccine to 11- to
      12-year-old female patients included considering it necessary to discuss
      sexuality before recommending HPV vaccine (risk ratio: 1.27 [95% confidence
      interval: 1.07-1.51]) and reporting more vaccine refusals among parents of
      younger versus older adolescents (risk ratio: 2.09 [95% confidence interval: 1.66
      2.81]). CONCLUSIONS: Eighteen months after licensure, the vast majority of
      pediatricians and family physicians reported offering HPV vaccine. Fewer
      physicians strongly recommended the vaccine for younger adolescents than for
      older adolescents, and physicians reported financial obstacles to vaccination.

PMID- 20679308
TI  - Bilirubin binding contributes to the increase in total bilirubin concentration in
      newborns with jaundice.
AB  - OBJECTIVE: This study tests the hypothesis that the hourly rate of increase in
      plasma bilirubin concentration (DeltaBT) would increase significantly with
      increasing binding avidity. METHODS: The plasma total bilirubin concentration
      (B(T)), unbound bilirubin concentration, and albumin concentration values for
      healthy newborns with jaundice (<or=100 hours of age, >or=35 weeks of gestation,
      and >or=2.5 kg at birth) were obtained from medical records. DeltaBT (in
      milligrams per deciliter per hour) was calculated as the slope of BT versus age
      (in hours). Binding avidity was quantified as the product of the albumin
      concentration and its bilirubin binding constant (K). Linear correlation was used
      to test the hypothesis that DeltaBT would increase significantly with K.albumin
      concentration. RESULTS: The ranges of BT, unbound bilirubin concentration,
      albumin concentration, and K values for the 21 patients studied were 7.6 to 28.5
      mg/dL, 0.53 to 2.52 microg/dL, 2.9 to 4.6 g/dL, and 38 to 163 L/micromol,
      respectively. DeltaBT correlated significantly with K.albumin concentration
      (r2=0.23; P=.026). CONCLUSIONS: Plasma bilirubin binding avidity contributes
      significantly to DeltaBT. This component of DeltaBT is associated with a lower
      risk of bilirubin neurotoxicity, and studies aimed at incorporating plasma
      bilirubin binding avidity measurements into the algorithms used for management of
      newborn jaundice seem warranted.

PMID- 20679309
TI  - Pediatric organ donation and transplantation policy statement: more questions,
      not answers.

PMID- 20679310
TI  - The American Academy of Pediatrics policy statement on organ donation.

PMID- 20679311
TI  - A morally questionable statement of policy.

PMID- 20679313
TI  - Adult outcome of extremely preterm infants.
AB  - Survival rates for extremely preterm (<28 weeks' gestational age) infants have
      increased and are approaching 3 in 4 with the advent of modern perinatal and
      neonatal intensive care. In contrast with some children with chronic diseases
      such as cystic fibrosis, most survivors of extreme prematurity have no ongoing
      health issues. However, as a group, they do have higher rates of adverse health
      outcomes, and more of them will present to pediatricians over time and,
      ultimately, to adult physicians as they grow older. Pediatricians can aid the
      transition to adult health care by being aware of the nutritional,
      cardiovascular, respiratory, motor, cognitive, psychiatric, and functional
      outcomes into adulthood of survivors of extreme prematurity.

PMID- 20679315
TI  - Foreword: pursuing excellence in early hearing detection and intervention
      programs.

PMID- 20679316
TI  - Evaluation of the universal newborn hearing screening and intervention program.
AB  - During the last 20 years, the number of infants evaluated for permanent hearing
      loss at birth has increased dramatically with universal newborn hearing screening
      and intervention (UNHSI) programs operating in all US states and many
      territories. One of the most urgent challenges of UNHSI programs involves loss to
      follow-up among families whose infants screen positive for hearing loss. We
      surveyed 55 state and territorial UNHSI programs and conducted site visits with 8
      state programs to evaluate progress in reaching program goals and to identify
      barriers to successful follow-up. We conclude that programs have made great
      strides in screening infants for hearing loss, but barriers to linking families
      of infants who do not pass the screening to further follow-up remain. We
      identified 4 areas in which there were barriers to follow-up (lack of service
      system capacity, lack of provider knowledge, challenges to families in obtaining
      services, and information gaps), as well as successful strategies used by some
      states to address barriers within each of these areas. We also identified 5 key
      areas for future program improvements: (1) improving data systems to support
      surveillance and follow-up activities; (2) ensuring that all infants have a
      medical home; (3) building capacity beyond identified providers; (4) developing
      family support services; and (5) promoting the importance of early detection.

PMID- 20679317
TI  - Federal privacy regulations and the provision of Early Hearing Detection and
      Intervention programs.
AB  - To be successful, Early Hearing Detection and Intervention (EHDI) programs
      require individually identifiable information about children to be shared among
      people who are responsible for screening, diagnosis, early intervention, family
      support, and medical home services. Pediatricians and other stakeholders in the
      EHDI process often point to federal laws that were passed to ensure privacy and
      confidentiality in health care and educational programs as major obstacles to
      achieving efficient and effective EHDI programs. In this article we summarize the
      provisions of 3 federal laws (the Health Insurance Portability and Accountability
      Act [HIPAA], the Family Education Rights and Privacy Act [FERPA], and Part C
      privacy regulations of the Individuals With Disabilities Education Act [IDEA])
      that most directly affect information-sharing in EHDI programs. We suggest
      strategies for sharing the information needed to operate successful EHDI programs
      while remaining in compliance with these laws, including obtaining signed
      parental consent to share information between providers, including an option on
      the individual family services plan for parents to permit sharing of the plan
      with pediatricians and other providers, and giving copies of all relevant test
      results to parents to share with providers as they wish.

PMID- 20679318
TI  - Preface: newborn hearing screening in the United States: historical perspective
      and future directions.

PMID- 20679319
TI  - Medicaid reimbursement of hearing services for infants and young children.
AB  - As newborn hearing-screening programs have expanded, more and more infants and
      young children need hearing services. Medicaid is one of the primary sources of
      funding for such services and, by law, must establish payment rates that are
      sufficient to enlist enough providers to provide services. In this study we
      compared 2005 Medicaid reimbursement rates for hearing services for infants and
      young children in 15 states with the payment rates for the same services by
      Medicare and commercially available health insurance. On average, Medicaid rates
      for the same services were only 67 as high as Medicare and only 38 as high as
      commercial fees. Furthermore, most Medicaid rates declined from 2000 to 2005, and
      many states did not have billing codes for a significant number of the hearing
      services needed by infants and young children. These factors likely contribute to
      infants and young children with hearing loss not being able to get the hearing
      services they need to benefit from early identification of hearing loss. These
      data also raise questions about the extent to which states are meeting the
      federal requirement that Medicaid payments be sufficient to enlist enough
      providers so that care and services are adequately available to the general
      population in the geographic area.

PMID- 20679320
TI  - Teleintervention for infants and young children who are deaf or hard-of-hearing.
AB  - Advancements in videoconferencing equipment and Internet-based tools for sharing
      information have resulted in widespread use of telemedicine for providing health
      care to people who live in remote areas. Given the limited supply of people
      trained to provide early-intervention services to infants and young children who
      are deaf or hard-of-hearing, and the fact that many families who need such
      services live significant distances from each other and from metropolitan areas,
      such "teleintervention" strategies hold promise for providing early-intervention
      services to children who are deaf or hard-of-hearing. Unfortunately, little is
      known about the cost-effectiveness of such teleintervention services. In this
      article we outline the rationale for using teleintervention services for children
      who are deaf or hard-of-hearing, describe a teleintervention program that has
      been serving relatively large numbers of children in Australia since 2002, and
      summarize what we know about the cost-effectiveness of such an approach. We
      conclude by summarizing the type of research needed to decide whether
      teleintervention should be used more frequently with children who are deaf or
      hard-of-hearing and the potential relevance of the teleintervention approach for
      the development of intervention systems in the United States.

PMID- 20679321
TI  - Improving follow-up to newborn hearing screening: a learning-collaborative
      experience.
AB  - Although approximately 95% of US newborns are now screened for hearing loss at
      birth, more than half of those who do not pass the screen lack a documented
      diagnosis. In an effort to improve the quality of the follow-up process, teams
      from 8 states participated in a breakthrough-series learning collaborative. Teams
      were trained in the Model for Improvement, a quality-improvement approach that
      entails setting clear aims, tracking results, identifying proven or promising
      change strategies, and the use of small-scale, rapid-cycle plan-do-study-act
      tests of these changes. Parents acted as equal partners with professionals in
      guiding system improvement. Teams identified promising change strategies
      including ensuring the correct identification of the primary care provider before
      discharge from the birthing hospital; obtaining a second contact number for each
      family before discharge; "scripting" the message given to families when an infant
      does not pass the initial screening test; and using a "roadmap for families" as a
      joint communication tool between parents and professionals to demonstrate each
      family's location on the "diagnostic journey." A learning-collaborative approach
      to quality improvement can be applied at a state-system level. Participants
      reported that the collaborative experience allowed them to move beyond a focus on
      improving their own service to improving connections between services and viewing
      themselves as part of a larger system of care. Ongoing quality-improvement
      efforts will require refinement of measures used to assess improvement,
      development of valid indicators of system performance, and an active role for
      families at all levels of system improvement.

PMID- 20679322
TI  - Accelerating evidence into practice for the benefit of children with early
      hearing loss.
AB  - Over the years, multiple groups have issued recommendations for newborn hearing
      screening, diagnosis, and intervention. In January 2008, the US Department of
      Health and Human Services held an invitational workshop at which more than 50
      national experts met for 2 days to consider ways to accelerate the movement of
      evidence-based recommendations into practice. Participants set priorities among
      existing recommendations, identified areas with the most promise and created a
      national blueprint to accelerate evidence into practice. Workshop participants
      adopted the "3T's Roadmap to Transform US Health Care" as the conceptual model
      for this work and used a modified Delphi process to identify high-priority
      recommendations in 5 areas (diagnosis, treatment, parental and public awareness,
      continuous quality improvement, and stewardship). A matrix of responsibility was
      developed to specify entities that could take action to implement these
      recommendations. Participants placed a high priority on measurement and
      recommended improved data-tracking of newborns after screening and creation of a
      limited set of national indicators to monitor progress toward evidence-based
      system goals. They also identified a greater role for parents and families in
      contributing to system transformation and a need for more culturally and
      linguistically appropriate resources. Targeting infants in the NICU for early
      testing and creating guidelines and resources for early intervention were
      additional priorities. Finally, the work group noted the need to create a
      stewardship function to monitor the progress of the entire system of care,
      disseminate reports, consider future research directions, and continue to develop
      critical cross-agency and public-private coordination of activities.

PMID- 20679323
TI  - Ensuring financial access to hearing AIDS for infants and young children.
AB  - Many young children with permanent hearing loss do not receive hearing aids and
      related professional services, in part because of public and private financing
      limitations. In 2006 the Children's Audiology Financing Workgroup was convened by
      the National Center for Hearing Assessment and Management to evaluate and make
      recommendations about public and private financing of hearing aids and related
      professional services for 0- to 3-year-old children. The workgroup recommended 4
      possible strategies for ensuring that all infants and young children with hearing
      loss have access to appropriate hearing aids and professional services: (1)
      clarify that the definition of assistive technology, which is a required service
      under Part C of the Individuals With Disabilities Education Act (IDEA), includes
      not only analog hearing aids but also digital hearing aids with appropriate
      features as needed by young children with hearing loss; (2) clarify for both
      state Medicaid and Children's Health Insurance Programs that digital hearing aids
      are almost always the medically necessary type of hearing aid required for
      infants and young children and should be covered under the Early and Periodic
      Screening, Diagnosis, and Treatment (EPSDT) program; (3) encourage the passage of
      private health insurance legislative mandates to require coverage of appropriate
      digital hearing aids and related professional services for infants and young
      children; and (4) establish hearing-aid loaner programs in every state. The costs
      of providing hearing aids to all 0- to 3-year old children in the United States
      are estimated here.

PMID- 20679324
TI  - Comparison of haematology, coagulation and clinical chemistry parameters in blood
      samples from the sublingual vein and vena cava in Sprague-Dawley rats.
AB  - The investigation of clinical pathology parameters (haematology, clinical
      chemistry and coagulation) is an important part of the preclinical evaluation of
      drug safety. However, the blood sampling method employed should avoid or minimize
      stress and injury in laboratory animals. In the present study, we compared the
      clinical pathology results from blood samples collected terminally from the vena
      cava (VC) immediately before necropsy with samples taken from the sublingual vein
      (VS) also prior to necropsy in order to determine whether the sampling method has
      an influence on clinical pathology parameters. Forty-six 12-week-old male Sprague
      Dawley rats were assigned to two groups (VC or VS; n = 23 each). All rats were
      anaesthetized with isoflurane prior to sampling. In the VC group, blood was
      withdrawn from the inferior VC. For VS sampling, the tongue was gently pulled out
      and the VS was punctured. The haematology, coagulation and clinical chemistry
      parameters were compared. Equivalence was established for 13 parameters, such as
      mean corpuscular volume, white blood cells and calcium. No equivalence was found
      for the remaining 26 parameters, although they were considered to be similar when
      compared with the historical data and normal ranges. The most conspicuous finding
      was that activated prothrombin time was 30.3% less in blood taken from the VC
      (16.6 +/- 0.89 s) than that in the VS samples (23.8 +/- 1.58 s). Summing up,
      blood sampling from the inferior VC prior to necropsy appears to be a suitable
      and reliable method for terminal blood sampling that reduces stress and injury to
      laboratory rats in preclinical drug safety studies.

PMID- 20679325
TI  - Building on the diversity and multiculturalism of health professional women
      around the world.
AB  - This article is based a presentation delivered to the Fifth Annual Building
      Global Alliances Symposium, "The Challenges of Migration for Health Professional
      Women," convened by CGFNS International, Philadelphia, PA, December 8, 2008.

PMID- 20679326
TI  - Imperial nursing: cross-cultural challenges for women in the health professions:
      a historical perspective.
AB  - This essay briefly examines some of the cross-cultural challenges that faced
      nurses in the Philippines, India, and South Africa in the context of 19th and
      20th century imperialism. During this time, nurses from colonizing countries
      served as agents of empire by helping to establish and reinforce American and
      European control in colonized societies. In doing so, they sought to instill the
      racial and gender hierarchies of their home countries in the colonial
      territories. But once these women moved to the colonies, they frequently found
      their preconceptions about femininity, sexuality, and race challenged in
      unexpected ways. The history of nursing in the age of empire is a story of good
      intentions mixed with cultural chauvinism, of professional rigor mixed with
      condescension, of devotion and generosity shaped and often distorted by ideas of
      gendered and racial conventions, and of ambitious reform crushed by an inability
      to think beyond the bounds of imperialism.

PMID- 20679327
TI  - Moving to understanding and change.
AB  - Creating an environment of inclusion for a culturally diverse nursing workforce
      is complex. The demographic shift in the country forecasted for over a decade has
      arrived. Today programs set up to recruit and retain multicultural and
      multilingual nursing staff are important organizational priorities. Employers
      want to build responsive and welcoming workplaces in which all feel engaged. This
      requires several things. Leaders must oversee system changes stimulated by a
      workforce similar to newly emerging cultural groups in their areas of service.
      The need exists for managers to possess non-ethnocentric management skills and
      are competent to take charge of teams motivated by a broad range of culture based
      values and beliefs. Diversity training, mentoring of staff and leadership
      development are benchmarks of an organization at the "tipping point" of change
      related to employing a diverse workforce.

PMID- 20679328
TI  - School Health Initiatives and Childhood Obesity: BMI screening and reporting.
AB  - The prevalence of childhood obesity has reached an epidemic status especially in
      the United States. Agencies such as the Institute of Medicine, Surgeon General's
      Office, and the American Academy of Pediatrics have called for action. Schools
      have been provided with guidelines to address obesity prevention. School-based
      body mass index screening and parent reporting programs have received a
      significant amount of attention in the literature. Intended to raise awareness
      for parents and provide a first step toward intervention for children who are
      overweight, there is to date limited outcomes of their success. However, one
      state, Arkansas, with mandated screening has reported success in that following
      screening in its schools, obesity rates were not increased. A significant concern
      with screening in schools is its potential harm to children around teasing, body
      image sensitivity, and possible unhealthy dieting. These controversial issues are
      explored, and recommendations are suggested for nursing's role in obesity
      prevention especially in schools.

PMID- 20679329
TI  - Child sexual abuse, links to later sexual exploitation/high-risk sexual behavior,
      and prevention/treatment programs.
AB  - This paper reviews the literature on the nature and incidence of child sexual
      abuse, explores the link between child sexual abuse and later sexual
      exploitation, and reviews the literature on prevention strategies and effective
      interventions in child sexual abuse services. Our understanding of the
      international epidemiology of child sexual abuse is considerably greater than it
      was just 10 years ago, and studies from around the world are examined. Childhood
      sexual abuse can involve a wide number of psychological sequelae, including low
      self-esteem, anxiety, and depression. Numerous studies have noted that child
      sexual abuse victims are vulnerable to later sexual revictimization, as well as
      the link between child sexual abuse and later engagement in high-risk sexual
      behaviour. Survivors of child sexual abuse are more likely to have multiple sex
      partners, become pregnant as teenagers, and experience sexual assault as adults.
      Various models which attempt to account for this inter-relationship are
      presented; most invoke mediating variables such as low self-esteem, drug/alcohol
      use, PTSD and distorted sexual development. Prevention strategies for child
      sexual abuse are examined including media campaigns, school-based prevention
      programmes, and therapy with abusers. The results of a number of meta-analyses
      are examined. However, researchers have identified significant methodological
      limitations in the extant research literature that impede the making of
      recommendations for implementing existing therapeutic programmes unreservedly.

PMID- 20679330
TI  - Multi-objective pairwise RNA sequence alignment.
AB  - MOTIVATION: With an increase in the number of known biological functions of non
      coding RNAs, the importance of RNA sequence alignment has risen. RNA sequence
      alignment problem has been investigated by many researchers as a mono-objective
      optimization problem where contributions from sequence similarity and secondary
      structure are taken into account through a single objective function. Since there
      is a trade-off between these two objective functions, usually we cannot obtain a
      single solution that has both the best sequence similarity score and the best
      structure score simultaneously. Multi-objective optimization is a widely used
      framework for the optimization problems with conflicting objective functions. So
      far, no one has examined how good alignments we can obtain by applying multi
      objective optimization to structural RNA sequence alignment problem. RESULTS: We
      developed a pairwise RNA sequence alignment program, Cofolga2mo, based on multi
      objective genetic algorithm (MOGA). We tested Cofolga2mo with a benchmark dataset
      which includes sequence pairs with a wide range of sequence identity, and we
      obtained at most 100 alignments for each inputted RNA sequence pair as an
      approximate set of weak Pareto optimal solutions. We found that the alignments in
      the approximate set give benchmark results comparable to those obtained by the
      state-of-the-art mono-objective RNA alignment algorithms. Moreover, we found that
      our algorithm is efficient in both time and memory usage compared to the other
      methods. AVAILABILITY: Our MOGA programs for structural RNA sequence alignment
      can be downloaded at http://rna.eit.hirosaki-u.ac.jp/cofolga2mo/.

PMID- 20679331
TI  - The CoFactor database: organic cofactors in enzyme catalysis.
AB  - MOTIVATION: Organic enzyme cofactors are involved in many enzyme reactions.
      Therefore, the analysis of cofactors is crucial to gain a better understanding of
      enzyme catalysis. To aid this, we have created the CoFactor database. RESULTS:
      CoFactor provides a web interface to access hand-curated data extracted from the
      literature on organic enzyme cofactors in biocatalysis, as well as automatically
      collected information. CoFactor includes information on the conformational and
      solvent accessibility variation of the enzyme-bound cofactors, as well as
      mechanistic and structural information about the hosting enzymes. AVAILABILITY:
      The database is publicly available and can be accessed at
      http://www.ebi.ac.uk/thornton-srv/databases/CoFactor.

PMID- 20679332
TI  - Exposing the co-adaptive potential of protein-protein interfaces through
      computational sequence design.
AB  - MOTIVATION: In nature, protein-protein interactions are constantly evolving under
      various selective pressures. Nonetheless, it is expected that crucial
      interactions are maintained through compensatory mutations between interacting
      proteins. Thus, many studies have used evolutionary sequence data to extract such
      occurrences of correlated mutation. However, this research is confounded by other
      evolutionary pressures that contribute to sequence covariance, such as common
      ancestry. RESULTS: Here, we focus exclusively on the compensatory mutations
      deriving from physical protein interactions, by performing large-scale
      computational mutagenesis experiments for >260 protein-protein interfaces. We
      investigate the potential for co-adaptability present in protein pairs that are
      always found together in nature (obligate) and those that are occasionally in
      complex (transient). By modeling each complex both in bound and unbound forms, we
      find that naturally transient complexes possess greater relative capacity for
      correlated mutation than obligate complexes, even when differences in interface
      size are taken into account.

PMID- 20679333
TI  - Multi-netclust: an efficient tool for finding connected clusters in multi
      parametric networks.
AB  - Multi-netclust is a simple tool that allows users to extract connected clusters
      of data represented by different networks given in the form of matrices. The tool
      uses user-defined threshold values to combine the matrices, and uses a
      straightforward, memory-efficient graph algorithm to find clusters that are
      connected in all or in either of the networks. The tool is written in C/C++ and
      is available either as a form-based or as a command-line-based program running on
      Linux platforms. The algorithm is fast, processing a network of > 10(6) nodes and
      10(8) edges takes only a few minutes on an ordinary computer. AVAILABILITY:
      http://www.bioinformatics.nl/netclust/.

PMID- 20679334
TI  - ISA software suite: supporting standards-compliant experimental annotation and
      enabling curation at the community level.
AB  - The first open source software suite for experimentalists and curators that (i)
      assists in the annotation and local management of experimental metadata from high
      throughput studies employing one or a combination of omics and other
      technologies; (ii) empowers users to uptake community-defined checklists and
      ontologies; and (iii) facilitates submission to international public
      repositories. AVAILABILITY AND IMPLEMENTATION: Software, documentation, case
      studies and implementations at http://www.isa-tools.org.

PMID- 20679335
TI  - PSExplorer: whole parameter space exploration for molecular signaling pathway
      dynamics.
AB  - MOTIVATION: Mathematical models of biological systems often have a large number
      of parameters whose combinational variations can yield distinct qualitative
      behaviors. Since it is intractable to examine all possible combinations of
      parameters for non-trivial biological pathways, it is required to have a
      systematic strategy to explore the parameter space in a computational way so that
      dynamic behaviors of a given pathway are estimated. RESULTS: We present
      PSExplorer, a computational tool for exploring qualitative behaviors and key
      parameters of molecular signaling pathways. Utilizing the Latin hypercube
      sampling and a clustering technique in a recursive paradigm, the software enables
      users to explore the whole parameter space of the models to search for robust
      qualitative behaviors. The parameter space is partitioned into sub-regions
      according to behavioral differences. Sub-regions showing robust behaviors can be
      identified for further analyses. The partitioning result presents a tree
      structure from which individual and combinational effects of parameters on model
      behaviors can be assessed and key factors of the models are readily identified.
      AVAILABILITY: The software, tutorial manual and test models are available for
      download at the following address: http://gto.kaist.ac.kr/~psexplorer.

PMID- 20679336
TI  - Transcriptional regulation by p53.
AB  - Inactivation of p53 is critical for the formation of most tumors. Illumination of
      the key function(s) of p53 protein in protecting cells from becoming cancerous is
      therefore a worthy goal. Arguably p53's most important function is to act as a
      transcription factor that directly regulates perhaps several hundred of the
      cell's RNA polymerase II (RNAP II)-transcribed genes, and indirectly regulates
      thousands of others. Indeed p53 is the most well studied mammalian transcription
      factor. The p53 tetramer binds to its response element where it can recruit
      diverse transcriptional coregulators such as histone modifying enzymes, chromatin
      remodeling factors, subunits of the mediator complex, and components of general
      transcription machinery and preinitiation complex (PIC) to modulate RNAPII
      activity at target loci (Laptenko and Prives 2006). The p53 transcriptional
      program is regulated in a stimulus-specific fashion (Murray-Zmijewski et al.
      2008; Vousden and Prives 2009), whereby distinct subsets of p53 target genes are
      induced in response to different p53-activating agents, likely allowing cells to
      tailor their response to different types of stress. How p53 is able to
      discriminate between these different loci is the subject of intense research.
      Here, we describe key aspects of the fundamentals of p53-mediated transcriptional
      regulation and target gene promoter selectivity.

PMID- 20679337
TI  - Zebrafish models of p53 functions.
AB  - Zebrafish models have significantly contributed to our understanding of
      vertebrate development and, more recently, human disease. The growing number of
      genetic tools available in zebrafish research has resulted in the identification
      of many genes involved in developmental and disease processes. In particular,
      studies in the zebrafish have clarified roles of the p53 tumor suppressor in the
      formation of specific tumor types, as well as roles of p53 family members during
      embryonic development. The zebrafish has also been instrumental in identifying
      novel mechanisms of p53 regulation and highlighting the importance of these
      mechanisms in vivo. This article will summarize how zebrafish models have been
      used to reveal numerous, important aspects of p53 function.

PMID- 20679338
TI  - Membrane transport in primitive cells.
AB  - Although model protocellular membranes consisting of monoacyl lipids are similar
      to membranes composed of contemporary diacyl lipids, they differ in at least one
      important aspect. Model protocellular membranes allow for the passage of polar
      solutes and thus can potentially support cell-to functions without the aid of
      transport machinery. The ability to transport polar molecules likely stems from
      increased lipid dynamics. Selectively permeable vesicle membranes composed of
      monoacyl lipids allow for many lifelike processes to emerge from a remarkably
      small set of molecules.

PMID- 20679339
TI  - Local conformation and dynamics of isoleucine in the collagenase cleavage site
      provide a recognition signal for matrix metalloproteinases.
AB  - The mechanism by which enzymes recognize the "uniform" collagen triple helix is
      not well understood. Matrix metalloproteinases (MMPs) cleave collagen after the
      Gly residue of the triplet sequence Gly~[Ile/Leu]-[Ala/Leu] at a single, unique,
      position along the peptide chain. Sequence analysis of types I-III collagen has
      revealed a 5-triplet sequence pattern in which the natural cleavage triplets are
      always flanked by a specific distribution of imino acids. NMR and MMP kinetic
      studies of a series of homotrimer peptides that model type III collagen have been
      performed to correlate conformation and dynamics at, and near, the cleavage site
      to collagenolytic activity. A peptide that models the natural cleavage site is
      significantly more active than a peptide that models a potential but non
      cleavable site just 2-triplets away and NMR studies show clearly that the Ile in
      the leading chain of the cleavage peptide is more exposed to solvent and less
      locally stable than the Ile in the middle and lagging chains. We propose that the
      unique local instability of Ile at the cleavage site in part arises from the
      placement of the conserved Pro at the P(3) subsite. NMR studies of peptides with
      Pro substitutions indicate that the local dynamics of the three chains are
      directly modulated by their proximity to Pro. Correlation of peptide activity to
      NMR data shows that a single locally unstable chain at the cleavage site, rather
      than two or three labile chains, is more favorable for cleavage by MMP-1 and may
      be the determining factor for collagen recognition.

PMID- 20679340
TI  - WSS25 inhibits growth of xenografted hepatocellular cancer cells in nude mice by
      disrupting angiogenesis via blocking bone morphogenetic protein (BMP)/Smad/Id1
      signaling.
AB  - The highly expressed Id1 (inhibitor of DNA binding/differentiation) protein
      promotes angiogenesis in HCC and is a well established target for anti
      angiogenesis therapeutic strategies. Heparan sulfate (HS) mimetics such as PI-88
      can abrogate HS-protein interactions to inhibit angiogenesis. Id1 is the direct
      downstream effector of bone morphogenetic proteins (BMPs), which are angiogenic
      and HS-binding proteins. Thus, targeting BMPs by HS mimetics may inhibit
      angiogenesis via attenuating Id1 expression. We report here that a HS mimetic
      WSS25 potently inhibited the tube formation of HMEC-1 cells on Matrigel and their
      migration. Meanwhile, WSS25 (25 MUg/ml) nearly completely blocked Id1 expression
      in the HMEC-1 cells as demonstrated by oligo-angiogenesis microarray analysis and
      further confirmed by RT-PCR and Western blotting. BMP/Smad/Id1 signaling also was
      blocked by WSS25 treatment in HMEC-1 cells. Importantly, Id1 knockdown in HMEC-1
      cells caused the disruption of their tube formation on Matrigel. By employing
      quartz crystal microbalance analysis, we found that WSS25 strongly bound to BMP2.
      Moreover, WSS25 impaired BMP2-induced tube formation of HMEC-1 cells on Matrigel
      and angiogenesis in Matrigel transplanted into C57BL6 mice. Furthermore, WSS25
      (100 mg/kg) abrogated the growth of HCC cells xenografted in male nude mice.
      Immunohistochemical analysis showed that both the expression of Id1 and the
      endothelial cell marker CD31 were lower in the WSS25-treated tumor tissue than in
      the control. Therefore, WSS25 is a potential drug candidate for HCC therapy as a
      tumor angiogenesis inhibitor.

PMID- 20679341
TI  - Tumor-supportive and osteoclastogenic changes induced by breast cancer-derived
      factors are reversed by inhibition of {gamma}-secretase.
AB  - During breast cancer metastasis to bone, tumor cells home to bone marrow, likely
      targeting the stem cell niche, and stimulate osteoclasts, which mediate
      osteolysis required for tumor expansion. Although osteoblasts contribute to the
      regulation of the hematopoietic stem cell niche and control osteoclastogenesis
      through production of proresorptive cytokine RANKL (receptor activator of NF
      kappaB ligand), their role in cancer metastases to bone is not fully understood.
      C57BL/6J mouse bone marrow cells were treated for 3-12 days with ascorbic acid
      (50 MUg/ml) in the presence or absence of 10% medium conditioned by breast
      carcinoma cells MDA-MB-231, 4T1, or MCF7. Treatment with cancer-derived factors
      resulted in a sustained 40-60% decrease in osteoblast differentiation markers,
      compared with treatment with ascorbic acid alone, and induced an osteoclastogenic
      change in the RANKL/osteoprotegerin ratio. Importantly, exposure of bone cells to
      breast cancer-derived factors stimulated the subsequent attachment of cancer
      cells to immature osteoblasts. Inhibition of gamma-secretase using
      pharmacological inhibitors DAPT and Compound E completely reversed cancer-induced
      osteoclastogenesis as well as cancer-induced enhancement of cancer cell
      attachment, identifying gamma-secretase activity as a key mediator of these
      effects. Thus, we have uncovered osteoblasts as critical intermediary of
      premetastatic signaling by breast cancer cells and pinpointed gamma-secretase as
      a robust target for developing therapeutics potentially capable of reducing both
      homing and progression of cancer metastases to bone.

PMID- 20679342
TI  - Nucleobindin 1 is a calcium-regulated guanine nucleotide dissociation inhibitor
      of G{alpha}i1.
AB  - Nucleobindin 1 (NUCB1) is a widely expressed multidomain calcium-binding protein
      whose precise physiological and biochemical functions are not well understood. We
      engineered and heterologously expressed a soluble form of NUCB1 (sNUCB1) and
      characterized its biophysical and biochemical properties. We show that sNUCB1
      exists as a dimer in solution and that each monomer binds two divalent calcium
      cations. Calcium binding causes conformational changes in sNUCB1 as judged by
      circular dichroism and fluorescence spectroscopy experiments. Earlier reports
      suggested that NUCB1 might interact with heterotrimeric G protein alpha subunits.
      We show that dimeric calcium-free sNUCB1 binds to expressed Galpha(i1) and that
      calcium binding inhibits the interaction. The binding of sNUCB1 to Galpha(i1)
      inhibits its basal rate of GDP release and slows its rate and extent of GTPgammaS
      uptake. Additionally, our tissue culture experiments show that sNUCB1 prevents
      receptor-mediated Galpha(i)-dependent inhibition of adenylyl cyclase. Thus, we
      conclude that sNUCB1 is a calcium-dependent guanine nucleotide dissociation
      inhibitor (GDI) for Galpha(i1). To our knowledge, sNUCB1 is the first example of
      a calcium-dependent GDI for heterotrimeric G proteins. We also show that the
      mechanism of GDI activity of sNUCB1 is unique and does not arise from the
      consensus GoLoco motif found in RGS proteins. We propose that cytoplasmic NUCB1
      might function to regulate heterotrimeric G protein trafficking and G protein
      coupled receptor-mediated signal transduction pathways.

PMID- 20679343
TI  - Spectroscopic studies of GSK3{beta} phosphorylation of the neuronal tau protein
      and its interaction with the N-terminal domain of apolipoprotein E.
AB  - Alzheimer disease neurons are characterized by extraneuronal plaques formed by
      aggregated amyloid-beta peptide and by intraneuronal tangles composed of
      fibrillar aggregates of the microtubule-associated Tau protein. Tau is mostly
      found in a hyperphosphorylated form in these tangles. Glycogen synthase kinase
      3beta (GSK3beta) is a proline-directed kinase generally considered as one of the
      major players that (hyper)phosphorylates Tau. The kinase phosphorylates mainly
      (Ser/Thr)-Pro motifs and is believed to require a priming activity by another
      kinase. Here, we use an in vitro phosphorylation assay and NMR spectroscopy to
      characterize in a qualitative and quantitative manner the phosphorylation of Tau
      by GSK3beta. We find that three residues can be phosphorylated (Ser-396, Ser-400,
      and Ser-404) by GSK3beta alone, without priming. Ser-404 is essential in this
      process, as its mutation to Ala prevents all activity of GSK3beta. However,
      priming enhances the catalytic efficacy of the kinase, as initial phosphorylation
      of Ser-214 by the cAMP-dependent protein kinase (PKA) leads to the rapid
      modification by GSK3beta of four regularly spaced additional sites. Because the
      regular incorporation of negative charges by GSK3beta leads to a potential
      parallel between phospho-Tau and heparin, we investigated its interaction with
      the heparin/low density lipoprotein receptor binding domain of human
      apolipoprotein E. We indeed observed an interaction between the GSK3beta-promoted
      regular phospho-pattern on Tau and the apolipoprotein E fragment but none in the
      absence of phosphorylation or the presence of an irregular phosphorylation
      pattern by the prolonged activity of PKA. Apolipoprotein E is therefore able to
      discriminate and interact with specific phosphorylation patterns of Tau.

PMID- 20679344
TI  - Probing the conformation of a prion protein fibril with hydrogen exchange.
AB  - A fragment of the prion protein, PrP(89-143, P101L), bearing a mutation
      implicated in familial prion disease, forms fibrils that have been shown to
      induce prion disease when injected intracerebrally into transgenic mice
      expressing full-length PrP containing the P101L mutation. In this study, we
      utilize amide hydrogen exchange measurements to probe the organization of the
      peptide in its fibrillar form. We determined the extent of hydrogen exchange
      first by tandem proteolysis, liquid chromatography, and mass spectrometry (HXMS)
      and then by exchange-quenched NMR. Although single amide resolution is afforded
      by NMR measurements, HXMS is well suited to the study of natural prions because
      it does not require labeling with NMR active isotopes. Thus, natural prions
      obtained from infected animals can be compared with model systems such as PrP(89
      143, P101L) studied here. In our study, we find two segments of sequence that
      display a high level of protection from exchange, residues 102-109 and 117-136.
      In addition, there is a region that displays exchange behavior consistent with
      the presence of a conformationally heterogeneous turn. We discuss our data with
      respect to several structural models proposed for infectious PrP aggregates and
      highlight HXMS as one of the few techniques well suited to studying natural
      prions.

PMID- 20679345
TI  - Anionic phospholipid interactions of the prion protein N terminus are minimally
      perturbing and not driven solely by the octapeptide repeat domain.
AB  - Although the N terminus of the prion protein (PrP(C)) has been shown to directly
      associate with lipid membranes, the precise determinants, biophysical basis, and
      functional implications of such binding, particularly in relation to endogenously
      occurring fragments, are unresolved. To better understand these issues, we
      studied a range of synthetic peptides: specifically those equating to the N1
      (residues 23-110) and N2 (23-89) fragments derived from constitutive processing
      of PrP(C) and including those representing arbitrarily defined component domains
      of the N terminus of mouse prion protein. Utilizing more physiologically relevant
      large unilamellar vesicles, fluorescence studies at synaptosomal pH (7.4) showed
      absent binding of all peptides to lipids containing the zwitterionic headgroup
      phosphatidylcholine and mixtures containing the anionic headgroups
      phosphatidylglycerol or phosphatidylserine. At pH 5, typical of early endosomes,
      quartz crystal microbalance with dissipation showed the highest affinity binding
      occurred with N1 and N2, selective for anionic lipid species. Of particular note,
      the absence of binding by individual peptides representing component domains
      underscored the importance of the combination of the octapeptide repeat and the N
      terminal polybasic regions for effective membrane interaction. In addition, using
      quartz crystal microbalance with dissipation and solid-state NMR, we
      characterized for the first time that both N1 and N2 deeply insert into the lipid
      bilayer with minimal disruption. Potential functional implications related to
      cellular stress responses are discussed.

PMID- 20679346
TI  - Influence of apolipoprotein (Apo) A-I structure on nascent high density
      lipoprotein (HDL) particle size distribution.
AB  - The principal protein of high density lipoprotein (HDL), apolipoprotein (apo) A
      I, in the lipid-free state contains two tertiary structure domains comprising an
      N-terminal helix bundle and a less organized C-terminal domain. It is not known
      how the properties of these domains modulate the formation and size distribution
      of apoA-I-containing nascent HDL particles created by ATP-binding cassette
      transporter A1 (ABCA1)-mediated efflux of cellular phospholipid and cholesterol.
      To address this issue, proteins corresponding to the two domains of human apoA-I
      (residues 1-189 and 190-243) and mouse apoA-I (residues 1-186 and 187-240)
      together with some human/mouse domain hybrids were examined for their abilities
      to form HDL particles when incubated with either ABCA1-expressing cells or
      phospholipid multilamellar vesicles. Incubation of human apoA-I with cells gave
      rise to two sizes of HDL particles (hydrodynamic diameter, 8 and 10 nm), and
      removal or disruption of the C-terminal domain eliminated the formation of the
      smaller particle. Variations in apoA-I domain structure and physical properties
      exerted similar effects on the rates of formation and sizes of HDL particles
      created by either spontaneous solubilization of phospholipid multilamellar
      vesicles or the ABCA1-mediated efflux of cellular lipids. It follows that the
      sizes of nascent HDL particles are determined at the point at which cellular
      phospholipid and cholesterol are solubilized by apoA-I; apparently, this is the
      rate-determining step in the overall ABCA1-mediated cellular lipid efflux
      process. The stability of the apoA-I N-terminal helix bundle domain and the
      hydrophobicity of the C-terminal domain are important determinants of both
      nascent HDL particle size and their rate of formation.

PMID- 20679347
TI  - Differential effects of ceramide and sphingosine 1-phosphate on ERM
      phosphorylation: probing sphingolipid signaling at the outer plasma membrane.
AB  - ERM proteins are regulated by phosphorylation of the most C-terminal threonine
      residue, switching them from an activated to an inactivated form. However, little
      is known about the control of this regulation. Previous work in our group
      demonstrated that secretion of acid sphingomyelinase acts upstream of ERM
      dephosphorylation, suggesting the involvement of sphingomyelin (SM) hydrolysis in
      ERM regulation. To define the role of specific lipids, we employed recombinant
      bacterial sphingomyelinase (bSMase) as a direct probe of SM metabolism at the
      plasma membrane. bSMase induced a rapid dose- and time-dependent decrease in ERM
      dephosphorylation. ERM dephosphorylation was driven by ceramide generation and
      not by sphingomyelin depletion, as shown using recombinant sphingomyelinase D.
      The generation of ceramide at the plasma membrane was sufficient for ERM
      regulation, and no intracellular SM hydrolysis was required, as was visualized
      using Venus-tagged lysenin probe, which specifically binds SM. Interestingly,
      hydrolysis of plasma membrane bSMase-induced ceramide using bacterial ceramidase
      caused ERM hyperphosphorylation and formation of cell surface protrusions. The
      effects of plasma membrane ceramide hydrolysis were due to sphingosine 1
      phosphate formation, as ERM phosphorylation was blocked by an inhibitor of
      sphingosine kinase and induced by sphingosine 1-phosphate. Taken together, these
      results demonstrate a new regulatory mechanism of ERM phosphorylation by
      sphingolipids with opposing actions of ceramide and sphingosine 1-phosphate. The
      approach also defines a tool kit to probe sphingolipid signaling at the plasma
      membrane.

PMID- 20679348
TI  - Suppression of ADAM17-mediated Lyn/Akt pathways induces apoptosis of human
      leukemia U937 cells: Bungarus multicinctus protease inhibitor-like protein-1
      uncovers the cytotoxic mechanism.
AB  - Cell surface proteases have been demonstrated to play an important role in
      facilitating cell invasion into the extracellular matrix and may contribute
      significantly to extracellular matrix degradation by metastatic cancer cells.
      Abundant expression of these enzymes is associated with poor prognosis. Thus,
      protease inhibitors that repress cell surface proteases may be applicable to
      cancer therapy. Because soybean Kunitz-type trypsin inhibitor has been found to
      induce apoptotic death of human leukemia Jurkat cells, anti-leukemia activity of
      Bungarus multicinctus protease inhibitor-like protein-1 (PILP-1) is thus
      examined. PILP-1 induced apoptosis of human leukemia U937 cells, characteristic
      of loss of mitochondrial membrane potential, degradation of procaspase-8, and
      production of t-Bid. FADD down-regulation neither restored viability of PILP-1
      treated cells nor attenuated production of active caspase-8 and t-Bid in PILP-1
      treated cells, suggesting that the death receptor-mediated pathway was not
      involved in the cytotoxicity of PILP-1. It was found that PILP-1-evoked p38 MAPK
      activation and ERK inactivation led to PILP-1-induced cell death and down
      regulation of ADAM17. Knockdown of ADAM17 by siRNA induced death of U937 cells
      and inactivation of Lyn and Akt. Immunoprecipitation suggested that ADAM17 and
      Lyn form complexes. Overexpression of ADAM17, LynY507F (gain of function), and
      constitutively active Akt suppressed the cytotoxic effects of PILP-1. PILP-1
      elicited inactivation of Lyn and Akt was abrogated in cells with overexpressed
      ADAM17 or LynY507F. Taken together, our data indicate that ADAM17-mediated
      activation of Lyn/Akt maintains the viability of U937 cells and that suppression
      of the pathway is responsible for PILP-1-induced apoptosis.

PMID- 20679349
TI  - A conserved region between the TPR and activation domains of p67phox participates
      in activation of the phagocyte NADPH oxidase.
AB  - The phagocyte NADPH oxidase, dormant in resting cells, is activated during
      phagocytosis to produce superoxide, a precursor of microbicidal oxidants. The
      membrane-integrated protein gp91(phox) serves as the catalytic core, because it
      contains a complete electron-transporting apparatus from NADPH to molecular
      oxygen for superoxide production. Activation of gp91(phox) requires the cytosolic
      proteins p67(phox), p47(phox), and Rac (a small GTPase). p67(phox), comprising
      526 amino acids, moves upon cell stimulation to the membrane together with
      p47(phox) and there interacts with Rac; these processes are prerequisite for
      gp91(phox) activation. Here we show that a region of p67(phox) (amino acids 190
      200) C-terminal to the Rac-binding domain is evolutionarily well conserved and
      participates in oxidase activation at a later stage in conjunction with an
      activation domain. Alanine substitution for Tyr-198, Leu-199, or Val-204
      abrogates the ability of p67(phox) to support superoxide production by gp91(phox)
      based oxidase as well as its related oxidases Nox1 and Nox3; the activation also
      involves other invariant residues such as Leu-193, Asp-197, and Gly-200.
      Intriguingly, replacement of Gln-192 by alanine or that of Tyr-198 by
      phenylalanine or tryptophan rather enhances superoxide production by gp91(phox)
      based oxidase, suggesting a tuning role for these residues. Furthermore, the
      Y198A/V204A or L199A/V204A substitution leads to not only a complete loss of the
      activity of the reconstituted oxidase system but also a significant decrease in
      p67(phox) interaction with the gp91(phox) NADPH-binding domain, although these
      mutations affect neither the protein integrity nor the Rac binding activity. Thus
      the extended activation domain of p67(phox) (amino acids 190-210) containing the
      D(Y/F)LGK motif plays an essential role in oxidase activation probably by
      interacting with gp91(phox).

PMID- 20679350
TI  - Impact of serum hepatocyte growth factor on treatment response to epidermal
      growth factor receptor tyrosine kinase inhibitors in patients with non-small cell
      lung adenocarcinoma.
AB  - PURPOSE: The epidermal growth factor receptor (EGFR) mutation status has emerged
      as a validated biomarker for predicting the response to treatment with EGFR
      tyrosine kinase inhibitors (EGFR-TKI) in patients with non-small cell lung
      cancer. However, the responses to EGFR-TKIs vary even among patients with EGFR
      mutations. We studied several other independently active biomarkers for EGFR-TKI
      treatment. EXPERIMENTAL DESIGN: We retrospectively analyzed the serum
      concentrations of 13 molecules in a cohort of 95 patients with non-small cell
      lung adenocarcinoma who received EGFR-TKI treatment at three centers. The
      pretreatment serum concentrations of amphiregulin, beta-cellulin, EGF, EGFR,
      epiregulin, fibroblast growth factor-basic, heparin-binding EGF-like growth
      factor, hepatocyte growth factor (HGF), platelet-derived growth factor beta
      polypeptide, placental growth factor, tenascin C, transforming growth factor
      alpha, and vascular endothelial growth factor (VEGF) were measured using enzyme
      linked immunosorbent assay and a multiplex immunoassay system. The associations
      between clinical outcomes and these molecules were evaluated. RESULTS: The
      concentrations of HGF and VEGF were significantly higher among patients with
      progressive disease than among those without progressive disease (P < 0.0001).
      HGF and VEGF were strongly associated with progression-free survival (PFS) and
      overall survival (OS) in a univariate Cox analysis (all tests for hazard ratio
      showed P < 0.0001). A stratified multivariate Cox model according to EGFR
      mutation status (mutant, n = 20; wild-type, n = 23; unknown, n = 52) showed that
      higher HGF levels were significantly associated with a shorter PFS and OS (P <
      0.0001 for both PFS and OS). These observations were also consistent in the
      subset analyses. CONCLUSIONS: Serum HGF was strongly related to the outcome of
      EGFR-TKI treatment. Our results suggest that the serum HGF level could be used to
      refine the selection of patients expected to respond to EGFR-TKI treatment,
      warranting further prospective study.

PMID- 20679352
TI  - The role of Hv1 and CatSper channels in sperm activation.
AB  - Elevations of sperm intracellular pH and Ca(2+) regulate sperm motility,
      chemotaxis, capacitation and the acrosome reaction, and play a vital role in the
      ability of the sperm cell to reach and fertilise the egg. In human spermatozoa,
      the flagellar voltage-gated proton channel Hv1 is the main H(+) extrusion pathway
      that controls sperm intracellular pH, and the pH-dependent flagellar Ca2(+)
      channel CatSper is the main pathway for Ca2(+) entry as measured by the whole
      cell patch clamp technique. Hv1 and CatSper channels are co-localized within the
      principal piece of the sperm flagellum. Hv1 is dedicated to proton extrusion from
      flagellum and is activated by membrane depolarisation, an alkaline extracellular
      environment, the endocannabinoid anandamide, and removal of extracellular zinc, a
      potent Hv1 blocker. The CatSper channel is strongly potentiated by intracellular
      alkalinisation. Since Hv1 and CatSper channels are located in the same
      subcellular domain, proton extrusion via Hv1 channels should induce
      intraflagellar alkalinisation and activate CatSper ion channels. Therefore the
      combined action of Hv1 and CatSper channels in human spermatozoa can induce
      elevation of both intracellular pH and Ca2(+) required for sperm activation in
      the female reproductive tract. Here, we discuss how Hv1 and CatSper channels
      regulate human sperm physiology and the differences in control of sperm
      intracellular pH and Ca2(+) between species.

PMID- 20679351
TI  - P2Y1 receptors mediate an activation of neuronal calcium-dependent K+ channels.
AB  - Molecularly defined P2Y receptor subtypes are known to regulate the functions of
      neurons through an inhibition of K(V)7 K(+) and Ca(V)2 Ca(2+) channels and via an
      activation or inhibition of Kir3 channels. Here, we searched for additional
      neuronal ion channels as targets for P2Y receptors. Rat P2Y(1) receptors were
      expressed in PC12 cells via an inducible expression system, and the effects of
      nucleotides on membrane currents and intracellular Ca(2+) were investigated. At a
      membrane potential of 30 mV, ADP induced transient outward currents in a
      concentration-dependent manner with half-maximal effects at 4 MUm. These currents
      had reversal potentials close to the K(+) equilibrium potential and changed
      direction when extracellular Na(+) was largely replaced by K(+), but remained
      unaltered when extracellular Cl() was changed. Currents were abolished by P2Y(1)
      antagonists and by blockade of phospholipase C. ADP also caused rises in
      intracellular Ca(2+), and ADP-evoked currents were abolished when inositol
      trisphosphate-sensitive Ca(2+) stores were depleted. Blockers of K(Ca)2, but not
      those of K(Ca)1.1 or K(Ca)3.1, channels largely reduced ADP-evoked currents. In
      hippocampal neurons, ADP also triggered outward currents at 30 mV which were
      attenuated by P2Y(1) antagonists, depletion of Ca(2+) stores, or a blocker of
      K(Ca)2 channels. These results demonstrate that activation of neuronal P2Y(1)
      receptors may gate Ca(2+)-dependent K(+) (K(Ca)2) channels via phospholipase C
      dependent increases in intracellular Ca(2+) and thereby define an additional
      class of neuronal ion channels as novel effectors for P2Y receptors. This
      mechanism may form the basis for the control of synaptic plasticity via P2Y(1)
      receptors.

PMID- 20679353
TI  - Visual and vestibular cue integration for heading perception in extrastriate
      visual cortex.
AB  - Natural behaviours, and hence neuronal populations, often combine multiple
      sensory cues to improve stimulus detectability or discriminability as we explore
      the environment. Here we review one such example of multisensory cue integration
      in the dorsal medial superior temporal area (MSTd) of the macaque visual cortex.
      Visual and vestibular cues about the direction of self-motion in the world
      (heading) are encoded by single multisensory neurons in MSTd. Most neurons tend
      to prefer lateral stimulus directions and, as they are broadly tuned, are most
      sensitive in discriminating heading directions around straight forward. Decoding
      of MSTd population activity shows that these neuronal properties can account for
      the fact that heading perception in humans and macaques is most precise for
      directions around straight forward, whereas heading sensitivity declines with
      increasing eccentricity of the reference direction. Remarkably, when heading is
      specified by both cues simultaneously, behavioural precision is improved in a
      manner that is predicted by statistically optimal (Bayesian) cue integration
      models. A subpopulation of multisensory MSTd cells with congruent visual and
      vestibular heading preferences also combines the cues near-optimally,
      establishing a potential neural substrate for behavioral cue integration.

PMID- 20679354
TI  - Is the efficiency of mammalian (mouse) skeletal muscle temperature dependent?
AB  - Myosin crossbridges in muscle convert chemical energy into mechanical energy.
      Reported values for crossbridge efficiency in human muscles are high compared to
      values measured in vitro using muscles of other mammalian species. Most in vitro
      muscle experiments have been performed at temperatures lower than mammalian
      physiological temperature, raising the possibility that human efficiency values
      are higher than those of isolated preparations because efficiency is temperature
      dependent. The aim of this study was to determine the effect of temperature on
      the efficiency of isolated mammalian (mouse) muscle. Measurements were made of
      the power output and heat production of bundles of muscle fibres from the fast
      twitch extensor digitorum longus (EDL) and slow-twitch soleus muscles during
      isovelocity shortening. Mechanical efficiency was defined as the ratio of power
      output to rate of enthalpy output, where rate of enthalpy output was the sum of
      the power output and rate of heat output. Experiments were performed at 20, 25
      and 30?C. Maximum efficiency of EDL muscles was independent of temperature; the
      highest value was 0.31}0.01 (n =5) at 30?C. Maximum efficiency of soleus
      preparations was slightly but significantly higher at 25 and 30?C than at 20?C;
      the maximum mean value was 0.48+/-0.02 (n =7) at 25?C. It was concluded that
      maximum mechanical efficiency of isolated mouse muscle was little affected by
      temperature between 20 and 30?C and that it is unlikely that differences in
      temperature account for the relatively high efficiency of human muscle in vivo
      compared to isolated mammalian muscles.

PMID- 20679355
TI  - Long-term inactivation particle for voltage-gated sodium channels.
AB  - Action potential generation is governed by the opening, inactivation, and
      recovery of voltage-gated sodium channels. A channel's voltage-sensing and pore
      forming alpha subunit bears an intrinsic fast inactivation particle that mediates
      both onset of inactivation upon membrane depolarization and rapid recovery upon
      repolarization. We describe here a novel inactivation particle housed within an
      accessory channel subunit (A-type FHF protein) that mediates rapid-onset, long
      term inactivation of several sodium channels. The channel-intrinsic and tethered
      FHF-derived particles, both situated at the cytoplasmic face of the plasma
      membrane, compete for induction of inactivation, causing channels to
      progressively accumulate into the long-term refractory state during multiple
      cycles of membrane depolarization. Intracellular injection of a short peptide
      corresponding to the FHF particle can reproduce channel long-term inactivation in
      a dose-dependent manner and can inhibit repetitive firing of cerebellar granule
      neurons. We discuss potential structural mechanisms of long-term inactivation and
      potential roles of A-type FHFs in the modulation of action potential generation
      and conduction.

PMID- 20679356
TI  - Prolonged ischaemia impairs muscle blood flow and oxygen uptake dynamics during
      subsequent heavy exercise.
AB  - Muscle oxygen uptake ( VO2,mus) dynamics at the onset of exercise can be affected
      by prior heavy exercise.We tested the hypothesis that elevated forearm blood flow
      (FBF) following prior circulatory occlusion would also be associated with
      accelerated VO2,mus dynamics during subsequent heavy hand-grip exercise. Ten
      trained young men performed 5 min of heavy hand-grip exercise at 30% MVC as a
      control (CON), and four additional heavy bouts after brief recovery from: (1)
      prior heavy exercise (Heavy A), (2) heavy exercise followed by 2 min occlusion
      (Heavy B), (3) 15 min occlusion (Heavy C), and (4) 5 min occlusion with 1 min of
      moderate exercise during occlusion (Heavy D). FBF was measured by ultrasound and
      arterial venous oxygen content difference was calculated from venous blood
      samples to estimate VO2,mus. FBF and VO2,mus dynamics were quantified from the
      rise time. All priming conditions elevated FBF immediately before the start of
      subsequent heavy bout (Heavy A: 207.4 +/-92.8, B: 207.8+/-75.8, C: 135.8+/-59.2,
      D: 199.5+/-59.0 vs. CON: 57.4+/-16.6mlmin-1, P <0.01). Unexpectedly, prior
      occlusion reduced FBF and O2 extraction at the onset of subsequent heavy exercise
      and consequently slowed VO2,mus dynamics (Heavy C: rise time=95.9+/-28.9 vs. CON:
      58.6+/-14.3 s, P <0.01). FBF and VO2,mus dynamics were faster in Heavy A, B and D
      compared to CON (P <0.05). Overall, there was a positive correlation between the
      rise times for VO2,mus and FBF (r2 =0.75) indicating that VO2,mus dynamics during
      heavy forearm exercise are linked to O2 delivery in trained young men. To
      investigate a possible mechanism for slower adaptation of VO2,mus following
      ischaemia, the prior occlusion condition was repeated after ingesting a high dose
      of ibuprofen. This resulted in restoration of the FBF and VO2,mus to control
      levels suggesting that a prostaglandin-mediated mechanism after occlusion
      retarded the adaptation of blood flow and oxygen consumption at the onset of
      subsequent heavy exercise.

PMID- 20679358
TI  - Metformin is associated with improved left ventricular diastolic function
      measured by tissue Doppler imaging in patients with diabetes.
AB  - OBJECTIVE: To examine the association between selected glucose-lowering
      medications and left ventricular (LV) diastolic function in patients with
      diabetes. DESIGN: Retrospective cohort study (years 2005-2008). METHODS:
      Echocardiograms of 242 patients with diabetes undergoing coronary angiography
      were analyzed. All patients had an LV ejection fraction (LVEF) >=20% and were
      without atrial fibrillation, bundle branch block, valvular disease, or cardiac
      pacemaker. Patients were grouped according to the use of metformin (n=56),
      sulfonylureas (n=43), insulin (n=61), and combination treatment (n=82). RESULTS:
      Mean age (66+/-10 years) and mean LVEF (45+/-11%) were similar across the groups.
      Mean isovolumic relaxation time (IVRT) was 66+/-31, 79+/-42, 69+/-23, and 66+/-29
      ms in metformin, sulfonylureas, insulin, and combination treatment groups
      respectively (P=0.4). Mean early diastolic longitudinal tissue velocity (e') was
      5.3+/-1.6, 4.6+/-1.6, 5.3+/-1.8, and 5.4+/-1.7 cm/s in metformin, sulfonylureas,
      insulin, and combination treatment groups (P=0.04). In adjusted linear regression
      models, the use of metformin was associated with a shorter IVRT (parameter
      estimate -9.9 ms, P=0.049) and higher e' (parameter estimate +0.52 cm/s, P=0.03),
      compared with no use of metformin. The effects of metformin were not altered by
      concomitant use of sulfonylureas or insulin (P for interactions >0.4).
      CONCLUSIONS: The use of metformin is associated with improved LV relaxation, as
      compared with no use of metformin.

PMID- 20679357
TI  - Adiposity and insulin resistance correlate with telomere length in middle-aged
      Arabs: the influence of circulating adiponectin.
AB  - OBJECTIVE: Studies in obesity have implicated adipocytokines in the development
      of insulin resistance, which in turn may lead to accelerated aging. In this
      study, we determined associations of chromosomal telomere length (TL) to markers
      of obesity and insulin resistance in middle-aged adult male and female Arabs with
      and without diabetes mellitus type 2 (DMT2). DESIGN AND METHODS: One hundred and
      ninety-three non-diabetic and DMT2 subjects without complications (97 males and
      96 females) participated in this cross-sectional study. Clinical data, as well as
      fasting blood samples, were collected. Serum glucose and lipid profile were
      determined using routine laboratory methods. Serum insulin, leptin, adiponectin,
      resistin, tumor necrosis factor-alpha, and PAI-1 were quantified using customized
      multiplex assay kits. High sensitive C-reactive protein (hsCRP) and angiotensin
      II (ANG II) were measured using ELISAs. Circulating leukocyte TL was examined by
      quantitative real-time PCR. RESULTS: Circulating chromosomal leukocyte TL had
      significant inverse associations with body mass index (BMI), systolic blood
      pressure, fasting insulin, homeostasis model assessment of insulin resistance
      (HOMA-IR), low-density lipoprotein (LDL)- and total cholesterol, ANG II and hsCRP
      levels. Adiponectin, BMI, systolic blood pressure, and LDL cholesterol predicted
      47% of the variance in TL (P<0.0001). HOMA-IR was the most significant predictor
      for TL in males, explaining 35% of the variance (P=0.01). In females, adiponectin
      accounted for 28% of the variance in TL (P=0.01). CONCLUSION: Obesity and insulin
      resistance are associated with chromosomal TL among adult Arabs. Evidence of
      causal relations needs further investigation. The positive association of
      adiponectin to TL has clinical implications as to the possible protective effects
      of this hormone from accelerated aging.

PMID- 20679359
TI  - Proinsulin levels in patients with pancreatic diabetes are associated with
      functional changes in insulin secretion rather than pancreatic beta-cell area.
AB  - INTRODUCTION: Hyperproinsulinaemia has been reported in patients with type 2
      diabetes. It is unclear whether this is due to an intrinsic defect in beta-cell
      function or secondary to the increased demand on the beta-cells. We investigated
      whether hyperproinsulinaemia is also present in patients with secondary diabetes,
      and whether proinsulin levels are associated with impaired beta-cell area or
      function. PATIENTS AND METHODS: Thirty-three patients with and without diabetes
      secondary to pancreatic diseases were studied prior to pancreatic surgery. Intact
      and total proinsulin levels were compared with the pancreatic beta-cell area and
      measures of insulin secretion and action. RESULTS: Fasting concentrations of
      total and intact proinsulin were similar in patients with normal, impaired
      (including two cases of impaired fasting glucose) and diabetic glucose tolerance
      (P=0.58 and P=0.98 respectively). There were no differences in the total
      proinsulin/insulin or intact proinsulin/insulin ratio between the groups (P=0.23
      and P=0.71 respectively). There was a weak inverse association between the total
      proinsulin/insulin ratio and pancreatic beta-cell area (r(2)=0.14, P=0.032),
      whereas the intact proinsulin/insulin ratio and the intact and total proinsulin
      levels were unrelated to beta-cell area. However, a strong inverse relationship
      between homeostasis model assessment index of beta-cell function and both the
      total and the intact proinsulin/insulin ratio was found (r(2)=0.55 and r(2)=0.48
      respectively). The association of insulin resistance (IR) with intact proinsulin
      was much weaker than the correlation with fasting insulin. CONCLUSIONS:
      Hyperproinsulinaemia is associated with defects in insulin secretion rather than
      a reduction in beta-cell area. The weak association between intact proinsulin and
      IR argues against the usefulness of this parameter in clinical practice.

PMID- 20679360
TI  - Avoiding false potassium results due to hyperleukocytosis.

PMID- 20679361
TI  - Appropriate cryoglobulin investigations.

PMID- 20679364
TI  - Clinical and regulatory standards for the evaluation of blood glucose monitoring
      systems.

PMID- 20679365
TI  - Effect of non-glucose sugars and haematocrit on glucose measurements with Roche
      Accu-Chek Performa glucose strips.

PMID- 20679366
TI  - Measurement of urinary metadrenaline and normetadrenaline by liquid
      chromatography tandem mass spectrometry for the diagnosis of phaeochromocytoma.
AB  - BACKGROUND: Measurement of metadrenalines has been recommended in the
      investigation of phaeochromocytoma. Urinary assays remain the most common;
      however, drug interference is still one of the main challenges for analytical
      systems. We have developed a liquid chromatography-tandem mass spectrometry (LC
      MS/MS) method for the quantification of total urinary normetadrenaline and total
      urinary metadrenaline, which does not require extraction procedures prior to
      analysis. METHOD: Total urinary normetadrenaline and total urinary metadrenaline
      were individually quantified by electrospray ionization in the multiple-reaction
      monitoring mode. Deuterated internal standards were used and an acid hydrolysis
      step was used to convert conjugated metabolites into free metadrenalines.
      Chromatographic separation was achieved using a Phenomenex Luna 3 micro PFP
      column followed by analysis on an API 3200 LC-MS/MS. RESULTS: Linearity was
      exhibited across the calibration range for both normetadrenaline (r = 1, P <
      0.0001) and metadrenaline (r = 1, P < 0.0001) with the limit of quantification of
      0.05 and 0.02 micromol/L, respectively. Intra-assay imprecision for both
      normetadrenaline and metadrenaline was less than 5.5% with % coefficient of
      variations of less than 4%. Inter-assay imprecision was less than 13%. Neither
      noradrenaline or adrenaline interfere with the assay as determined by the spiking
      of samples with high concentrations of noradrenaline or adrenaline (P > 0.05).
      Acceptable analytical performance was seen with comparison to a high-performance
      liquid chromatography method and on External Quality Assessment returns.
      CONCLUSIONS: An analytically simple and sensitive method has been developed and
      evaluated for the analysis of total urinary normetadrenaline and total urinary
      metadrenaline which is now in routine use.

PMID- 20679367
TI  - Mechanism of egg envelope digestion by hatching enzymes, HCE and LCE in medaka,
      Oryzias latipes.
AB  - Hatching of medaka embryos from the fertilized egg envelope involves two enzymes,
      HCE and LCE. HCE swells the envelope and then LCE completely dissolves it. We
      determined HCE and LCE cleavage sites on the egg envelope that are primarily
      constructed of two groups of subunit proteins, ZI-1,2 and ZI-3. HCE and LCE
      cleaved different target sequences on the egg envelope proteins but shared one
      common cleavage site. HCE cleaved the N-terminal region of ZI-1,2 and ZI-3,
      mainly the Pro-Xaa-Yaa repeat sequence of ZI-1,2 into hexapeptides, but not the
      site within a zona pellucida (ZP) domain that is considered to be the core
      structure of the egg envelope. The cleavage of these N-terminal regions results
      in swelling and softening of the envelope. LCE cleaved the middle of the ZP
      domain of ZI-1,2, in addition to the upstream of the trefoil domain of ZI-1,2 and
      the ZP domain of ZI-3. This middle site is in the intervening sequence connecting
      two subdomains of the ZP domain. Cleaving this site would result in the
      solubilization of the swollen egg envelope by the disruption of the filamentous
      structure that is thought to be formed by the non-covalent polymerization of ZP
      domains.

PMID- 20679368
TI  - Identification of proteins that may directly interact with human RPA.
AB  - RPA, which consisted of three subunits (RPA1, 2 and 3), plays essential roles in
      DNA transactions. At the DNA replication forks, RPA binds to single-stranded DNA
      region to stabilize the structure and to assemble other replication proteins.
      Interactions between RPA and several replication proteins have been reported but
      the analysis is not comprehensive. We systematically performed the qualitative
      analysis to identify RPA interaction partners to understand the protein-protein
      interaction at the replication forks. We expressed in insect cells the three
      subunits of human RPA, together with one replication protein, which is present at
      the forks under normal conditions and/or under the replication stress conditions,
      to examine the interaction. Among 30 proteins examined in total, it was found
      that at least 14 proteins interacted with RPA. RPA interacted with MCM3-7, MCM-BP
      and CDC45 proteins among the proteins that play roles in the initiation and the
      elongation of the DNA replication. RPA bound with TIPIN, CLASPIN and RAD17, which
      are involved in the DNA replication checkpoint functions. RPA also bound with
      cyclin-dependent kinases and an amino-terminal fragment of Rb protein that
      negatively regulates DNA replication. These results suggest that RPA interacts
      with the specific proteins among those that play roles in the regulation of the
      replication fork progression.

PMID- 20679369
TI  - Demonstrating polymorphic miRNA-mediated gene regulation in vivo: application to
      the g+6223G->A mutation of Texel sheep.
AB  - We herein describe the development of a biochemical method to evaluate the effect
      of single nucleotide polymorphisms (SNPs) in target genes on their regulation by
      microRNAs in vivo. The method is based on the detection of allelic imbalance in
      RNAs coimmunoprecipitated with AGO proteins from tissues of heterozygous
      individuals. We characterize the performances of our approach using a model
      system in a cell culture, and then apply it successfully to prove that the 3'UTR
      g+6223G-->A mutation operates by promoting RISC-dependent down-regulation of
      myostatin (MSTN) in skeletal muscle of Texel sheep.

PMID- 20679370
TI  - In vitro screen to obtain widespread, transgenic expression in the mouse.

PMID- 20679371
TI  - Staining for acetylcholinesterase in brain sections.

PMID- 20679373
TI  - Quick and easy fixation of plant tissues for scanning electron microscopy (SEM).

PMID- 20679372
TI  - Choline acetyltransferase staining in brain sections.

PMID- 20679374
TI  - Protein complex binding to promoter DNA: immobilized template assay.

PMID- 20679375
TI  - Lysis of cultured cells for immunoprecipitation.

PMID- 20679376
TI  - Lysis of cultured animal cells, yeast, and bacteria for immunoblotting.

PMID- 20679377
TI  - Preparation of poly(lactic acid) (PLA) and poly(ethylene oxide) (PEO)
      nanoparticles as carriers for gene delivery.

PMID- 20679378
TI  - Dissection of Drosophila larval body-wall muscles.

PMID- 20679379
TI  - Immunocytochemical staining of Drosophila larval body-wall muscles.

PMID- 20679380
TI  - Fm1-43 labeling of Drosophila larval neuromuscular junctions.

PMID- 20679381
TI  - Internalization and trafficking assay for Drosophila larvae.

PMID- 20679382
TI  - Activity paradigm to induce Drosophila larval neuromuscular junction growth.

PMID- 20679383
TI  - Electron microscopy of Drosophila larval neuromuscular junctions.

PMID- 20679384
TI  - Preparation of very-high-yield recombinant proteins using novel high-cell-density
      bacterial expression methods.

PMID- 20679385
TI  - Multi-layer in vivo imaging of neocortex using a microprism.

PMID- 20679386
TI  - Analysis of targeted chromosomal deletions induced by zinc finger nucleases.

PMID- 20679387
TI  - Quantitative estimation of multiple miRNAs and mRNAs from a single cell.

PMID- 20679388
TI  - Potassium permanganate probing of Pol II open complexes.

PMID- 20679389
TI  - High-throughput microscopy using live mammalian cells.

PMID- 20679390
TI  - The epigenome and the mitochondrion: bioenergetics and the environment
      [corrected].
AB  - In the July 15, 2010, issue of Genes & Development, Yoon and colleagues (pp. 1507
      1518) report that, in a siRNA knockdown survey of 6363 genes in mouse C2C12
      cells, they discovered 150 genes that regulated mitochondrial biogenesis and
      bioenergetics. Many of these genes have been studied previously for their
      importance in regulating transcription, protein and nucleic acid modification,
      and signal transduction. Some notable examples include Brac1, Brac2, Pax4, Sin3A,
      Fyn, Fes, Map2k7, Map3k2, calmodulin 3, Camk1, Ube3a, and Wnt. Yoon and
      colleagues go on to validate their observations by extensively documenting the
      role of Wnt signaling in the regulation of mitochondrial function.

PMID- 20679391
TI  - Antisense oligonucleotides and spinal muscular atrophy: skipping along.
AB  - Antisense oligonucleotides (ASOs) can be used to alter the splicing of a gene and
      either restore production of a required protein or eliminate a toxic product. In
      this issue of Genes & Development, Hua and colleagues (pp. 1634-1644) show that
      ASOs directed against an intron splice silencer (ISS) in the survival motor
      neuron 2 (SMN2) gene alter the amount of full-length SMN transcript in the
      nervous system, restoring SMN to levels that could correct spinal muscular
      atrophy (SMA).

PMID- 20679393
TI  - RNA methylation by Dnmt2 protects transfer RNAs against stress-induced cleavage.
AB  - Dnmt2 proteins are the most conserved members of the DNA methyltransferase enzyme
      family, but their substrate specificity and biological functions have been a
      subject of controversy. We show here that, in addition to tRNA(Asp-GTC), tRNA(Val
      AAC) and tRNA(Gly-GCC) are also methylated by Dnmt2. Drosophila Dnmt2 mutants
      showed reduced viability under stress conditions, and Dnmt2 relocalized to stress
      granules following heat shock. Strikingly, stress-induced cleavage of tRNAs was
      Dnmt2-dependent, and Dnmt2-mediated methylation protected tRNAs against
      ribonuclease cleavage. These results uncover a novel biological function of Dnmt2
      mediated tRNA methylation, and suggest a role for Dnmt2 enzymes during the
      biogenesis of tRNA-derived small RNAs.

PMID- 20679392
TI  - The Mdm2-p53 relationship evolves: Mdm2 swings both ways as an oncogene and a
      tumor suppressor.
AB  - Mdm2 has been well characterized as a negative regulator of the tumor suppressor
      p53. Recent studies have shown that Mdm2 is activated in response to a variety of
      oncogenic pathways independent of p53. Although its role as an oncogene via
      suppression of p53 function remains clear, growing evidence argues for p53
      independent effects, as well as the remarkable possibility that Mdm2 has tumor
      suppressor functions in the appropriate context. Hence, Mdm2 is proving to be a
      key player in human cancer in its own right, and thus an important target for
      therapeutic intervention.

PMID- 20679394
TI  - Verrocchio, a Drosophila OB fold-containing protein, is a component of the
      terminin telomere-capping complex.
AB  - Drosophila telomeres are elongated by transposition of specialized retroelements
      rather than telomerase activity, and are assembled independently of the terminal
      DNA sequence. Drosophila telomeres are protected by terminin, a complex that
      includes the HOAP (Heterochromatin Protein 1/origin recognition complex
      associated protein) and Moi (Modigliani) proteins and shares the properties of
      human shelterin. Here we show that Verrocchio (Ver), an
      oligonucleotide/oligosaccharide-binding (OB) fold-containing protein related to
      Rpa2/Stn1, interacts physically with HOAP and Moi, is enriched only at telomeres,
      and prevents telomere fusion. These results indicate that Ver is a new terminin
      component; we speculate that, concomitant with telomerase loss, Drosophila
      evolved terminin to bind chromosome ends independently of the DNA sequence.

PMID- 20679395
TI  - Apoptosis of leukocytes triggered by acute DNA damage promotes lymphoma
      formation.
AB  - Apoptosis triggered by p53 upon DNA damage secures removal of cells with
      compromised genomes, and is thought to prevent tumorigenesis. In contrast, we
      provide evidence that p53-induced apoptosis can actively drive tumor formation.
      Mice defective in p53-induced apoptosis due to loss of its proapoptotic target
      gene, puma, resist gamma-irradiation (IR)-induced lymphomagenesis. In wild-type
      animals, repeated irradiation injury-induced expansion of hematopoietic
      stem/progenitor cells (HSCs) leads to lymphoma formation. Puma(-/-) HSCs,
      protected from IR-induced cell death, show reduced compensatory proliferation and
      replication stress-associated DNA damage, and fail to form thymic lymphomas,
      demonstrating that the maintenance of stem/progenitor cell homeostasis is
      critical to prevent IR-induced tumorigenesis.

PMID- 20679396
TI  - Apoptosis-promoted tumorigenesis: gamma-irradiation-induced thymic
      lymphomagenesis requires Puma-driven leukocyte death.
AB  - Although tumor development requires impaired apoptosis, we describe a novel
      paradigm of apoptosis-dependent tumorigenesis. Because DNA damage triggers
      apoptosis through p53-mediated induction of BH3-only proteins Puma and Noxa, we
      explored their roles in gamma-radiation-induced thymic lymphomagenesis.
      Surprisingly, whereas Noxa loss accelerated it, Puma loss ablated tumorigenesis.
      Tumor suppression by Puma deficiency reflected its protection of leukocytes from
      gamma-irradiation-induced death, because their glucocorticoid-mediated decimation
      in Puma-deficient mice activated cycling of stem/progenitor cells and restored
      thymic lymphomagenesis. Our demonstration that cycles of cell attrition and
      repopulation by stem/progenitor cells can drive tumorigenesis has parallels in
      human cancers, such as therapy-induced malignancies.

PMID- 20679397
TI  - Defective erythroid differentiation in miR-451 mutant mice mediated by 14-3
      3zeta.
AB  - Erythrocyte formation occurs throughout life in response to cytokine signaling.
      We show that microRNA-451 (miR-451) regulates erythropoiesis in vivo. Mice
      lacking miR-451 display a reduction in hematrocrit, an erythroid differentiation
      defect, and ineffective erythropoiesis in response to oxidative stress. 14-3
      3zeta, an intracellular regulator of cytokine signaling that is repressed by miR
      451, is up-regulated in miR-451(-/-) erythroblasts, and inhibition of 14-3-3zeta
      rescues their differentiation defect. These findings reveal an essential role of
      14-3-3zeta as a mediator of the proerythroid differentiation actions of miR-451,
      and highlight the therapeutic potential of miR-451 inhibitors.

PMID- 20679398
TI  - miR-451 protects against erythroid oxidant stress by repressing 14-3-3zeta.
AB  - The bicistronic microRNA (miRNA) locus miR-144/451 is highly expressed during
      erythrocyte development, although its physiological roles are poorly understood.
      We show that miR-144/451 ablation in mice causes mild erythrocyte instability and
      increased susceptibility to damage after exposure to oxidant drugs. This
      phenotype is deeply conserved, as miR-451 depletion synergizes with oxidant
      stress to cause profound anemia in zebrafish embryos. At least some protective
      activities of miR-451 stem from its ability to directly suppress production of 14
      3-3zeta, a phospho-serine/threonine-binding protein that inhibits nuclear
      accumulation of transcription factor FoxO3, a positive regulator of erythroid
      anti-oxidant genes. Thus, in miR-144/451(-/-) erythroblasts, 14-3-3zeta
      accumulates, causing partial relocalization of FoxO3 from nucleus to cytoplasm
      with dampening of its transcriptional program, including anti-oxidant-encoding
      genes Cat and Gpx1. Supporting this mechanism, overexpression of 14-3-3zeta in
      erythroid cells and fibroblasts inhibits nuclear localization and activity of
      FoxO3. Moreover, shRNA suppression of 14-3-3zeta protects miR-144/451(-/-)
      erythrocytes against peroxide-induced destruction, and restores catalase
      activity. Our findings define a novel miRNA-regulated pathway that protects
      erythrocytes against oxidant stress, and, more generally, illustrate how a miRNA
      can influence gene expression by altering the activity of a key transcription
      factor.

PMID- 20679399
TI  - Developmental stage-specific interplay of GATA1 and IGF signaling in fetal
      megakaryopoiesis and leukemogenesis.
AB  - Oncogene-mediated transformation of hematopoietic cells has been studied
      extensively, but little is known about the molecular basis for restriction of
      oncogenes to certain target cells and differential cellular context-specific
      requirements for oncogenic transformation between infant and adult leukemias.
      Understanding cell type-specific interplay of signaling pathways and oncogenes is
      essential for developing targeted cancer therapies. Here, we address the vexing
      issue of how developmental restriction is achieved in Down syndrome acute
      megakaryoblastic leukemia (DS-AMKL), characterized by the triad of fetal origin,
      mutated GATA1 (GATA1s), and trisomy 21. We demonstrate overactivity of insulin
      like growth factor (IGF) signaling in authentic human DS-AMKL and in a DS-AMKL
      mouse model generated through retroviral insertional mutagenesis. Fetal but not
      adult megakaryocytic progenitors are dependent on this pathway. GATA1 restricts
      IGF-mediated activation of the E2F transcription network to coordinate
      proliferation and differentiation. Failure of a direct GATA1-E2F interaction in
      mutated GATA1s converges with overactive IGF signaling to promote cellular
      transformation of DS fetal progenitors, revealing a complex, fetal stage-specific
      regulatory network. Our study underscores context-dependent requirements during
      oncogenesis, and explains resistance to transformation of ostensibly similar
      adult progenitors.

PMID- 20679400
TI  - IL-2 reverses established type 1 diabetes in NOD mice by a local effect on
      pancreatic regulatory T cells.
AB  - Regulatory T cells (T reg cells) play a major role in controlling the pathogenic
      autoimmune process in type 1 diabetes (T1D). Interleukin 2 (IL-2), a cytokine
      which promotes T reg cell survival and function, may thus have therapeutic
      efficacy in T1D. We show that 5 d of low-dose IL-2 administration starting at the
      time of T1D onset can reverse established disease in NOD (nonobese diabetic)
      mice, with long-lasting effects. Low-dose IL-2 increases the number of T reg
      cells in the pancreas and induces expression of T reg cell-associated proteins
      including Foxp3, CD25, CTLA-4, ICOS (inducible T cell costimulator), and GITR
      (glucocorticoid-induced TNF receptor) in these cells. Treatment also suppresses
      interferon gamma production by pancreas-infiltrating T cells. Transcriptome
      analyses show that low-dose IL-2 exerts much greater influence on gene expression
      of T reg cells than effector T cells (T eff cells), suggesting that nonspecific
      activation of pathogenic T eff cells is less likely. We provide the first
      preclinical data showing that low-dose IL-2 can reverse established T1D,
      suggesting that this treatment merits evaluation in patients with T1D.

PMID- 20679401
TI  - Soluble HIV-1 Env trimers in adjuvant elicit potent and diverse functional B cell
      responses in primates.
AB  - Broadly neutralizing antibodies (bNAbs) against the HIV-1 envelope glycoproteins
      (Envs) have proven difficult to elicit by immunization. Therefore, to identify
      effective Env neutralization targets, efforts are underway to define the
      specificities of bNAbs in chronically infected individuals. For a prophylactic
      vaccine, it is equally important to define the immunogenic properties of the
      heavily glycosylated Env in healthy primates devoid of confounding HIV-induced
      pathogenic factors. We used rhesus macaques to investigate the magnitude and
      kinetics of B cell responses stimulated by Env trimers in adjuvant. Robust Env
      specific memory B cell responses and high titers of circulating antibodies
      developed after trimer inoculation. Subsequent immunizations resulted in
      significant expansion of Env-specific IgG-producing plasma cell populations and
      circulating Abs that displayed increasing avidity and neutralization capacity.
      The neutralizing activity elicited with the regimen used was, in most aspects,
      superior to that elicited by a regimen based on monomeric Env immunization in
      humans. Despite the potency and breadth of the trimer-elicited response,
      protection against heterologous rectal simian-HIV (SHIV) challenge was modest,
      illustrating the challenge of eliciting sufficient titers of cross-reactive
      protective NAbs in mucosal sites. These data provide important information for
      the design and evaluation of vaccines aimed at stimulating protective HIV-1
      immune responses in humans.

PMID- 20679402
TI  - Human anti-HIV-neutralizing antibodies frequently target a conserved epitope
      essential for viral fitness.
AB  - The identification and characterization of conserved epitopes on the HIV-1 viral
      spike that are immunogenic in humans and targeted by neutralizing antibodies is
      an important step in vaccine design. Antibody cloning experiments revealed that
      32% of all HIV-neutralizing antibodies expressed by the memory B cells in
      patients with high titers of broadly neutralizing antibodies recognize one or
      more "core" epitopes that were not defined. Here, we show that anti-core
      antibodies recognize a single conserved epitope on the gp120 subunit. Amino acids
      D474, M475, R476, which are essential for anti-core antibody binding, form an
      immunodominant triad at the outer domain/inner domain junction of gp120. The
      mutation of these residues to alanine impairs viral fusion and fitness. Thus, the
      core epitope, a frequent target of anti-HIV-neutralizing antibodies, including
      the broadly neutralizing antibody HJ16, is conserved and indispensible for viral
      infectivity. We conclude that the core epitope should be considered as a target
      for vaccine design.

PMID- 20679403
TI  - Anti-CD3 therapy permits regulatory T cells to surmount T cell receptor-specified
      peripheral niche constraints.
AB  - Treatment with anti-CD3 is a promising therapeutic approach for autoimmune
      diabetes, but its mechanism of action remains unclear. Foxp3(+) regulatory T (T
      reg) cells may be involved, but the evidence has been conflicting. We
      investigated this issue in mice derived from the NOD model, which were engineered
      so that T reg populations were perturbed, or could be manipulated by acute
      ablation or transfer. The data highlighted the involvement of Foxp3(+) cells in
      anti-CD3 action. Rather than a generic influence on all T reg cells, the
      therapeutic effect seemed to involve an approximately 50-60-fold expansion of
      previously constrained T reg cell populations; this expansion occurred not
      through conversion from Foxp3(-) conventional T (T conv) cells, but from a
      proliferative expansion. We found that T reg cells are normally constrained by
      TCR-specific niches in secondary lymphoid organs, and that intraclonal
      competition restrains their possibility for conversion and expansion in the
      spleen and lymph nodes, much as niche competition limits their selection in the
      thymus. The strong perturbations induced by anti-CD3 overcame these niche
      limitations, in a process dependent on receptors for interleukin-2 (IL-2) and IL
      7.

PMID- 20679404
TI  - An innately dangerous balancing act: intestinal homeostasis, inflammation, and
      colitis-associated cancer.
AB  - Inflammatory bowel disease (IBD) is characterized by dysregulated immune
      responses to the intestinal microbiota, and by chronic intestinal inflammation.
      Several recent studies demonstrate the importance of innate microbial recognition
      by immune and nonimmune cells in the gut. Paradoxically, either diminished or
      exacerbated innate immune signaling may trigger the breakdown of intestinal
      homeostasis, leading to IBD and colitis-associated cancer (CAC). This dichotomy
      may reflect divergent functional roles for immune sensing in intestinal
      epithelial cells and leukocytes, which may vary with distinct disease mechanisms.

PMID- 20679405
TI  - Identification of determinants for weight reduction in overweight and obese
      children and adolescents.
AB  - We conducted a pilot trial of electronic technology integrated into the treatment
      of children and adolescents who are overweight or obese. A total of 30 patients
      (mean age 14 years, mean BMI 32.7 kg/m(2)) were admitted to our hospital to
      participate in a structured treatment and teaching programme (STTP). To assess
      physical activity and eating habits, a mobile motion sensor board (MoSeBo) or a
      sensor for physical activity, integrated into a mobile phone with digital camera
      (DiaTrace) was used. Over an average period of four days of monitoring, the mean
      intensity (15.4 activity units) and duration of physical activity (267 min/d)
      were recorded with the mobile sensors. The mean time spent walking was 64 min/d,
      running 11 min/d, cycling 24 min/d and car driving 21 min/d. There were
      significant differences (P < 0.001) between self-reported physical activity and
      objective assessment: in general the duration of physical activity documented by
      children and adolescents was much higher than the objective assessment.
      Similarly, the real caloric intake was higher than the self-estimates (P =
      0.085). A multivariate analysis showed that the following variables were
      significantly associated with weight reduction in the hospital STTP (R-squared =
      0.59): high motivation, intrafamilial conflicts, duration of physical activity
      assessed with the MoSeBo/DiaTrace system, and the body fat mass at onset of
      therapy. All children and adolescents included in the trial completed it.
      Although the MoSeBo/DiaTrace system was used for a relatively short period in
      each patient, the high acceptance demonstrated that it could be integrated into
      therapy easily.

PMID- 20679406
TI  - Designing and remotely testing mobile diabetes video games.
AB  - We have investigated game design and usability for three mobile phone video games
      designed to deliver diabetes education. The games were refined using focus
      groups. Six people with diabetes participated in the first focus group and five
      in the second. Following the focus groups, we incorporated the new findings into
      the game design, and then conducted a field test to evaluate the games in the
      context in which they would actually be used. Data were collected remotely about
      game usage by eight people with diabetes. The testers averaged 45 seconds per
      question and answered an average of 50 total nutrition questions each. They self
      reported playing the game for 10-30 min, which coincided with the measured
      metrics of the game. Mobile games may represent a promising new way to engage the
      user and deliver relevant educational content.

PMID- 20679407
TI  - Telemedicine in vascular surgery: clinical experience in a single centre.
AB  - Over a three-year period we performed 630 carotid endarterectomy procedures in
      588 patients. From these we selected 90 patients (group A) who fulfilled the
      criteria for discharge one day after surgery. These patients were given an
      electronic blood pressure meter, a video phone for use at home and an
      antihypertensive drug (amlodipine). Using web-based video conferencing, we
      monitored the patients every 4 hours for the first two days. The other 498
      patients (group B) were discharged on the second postoperative day. There were no
      significant differences between the groups in demographic characteristics, risk
      factors, carotid lesions, operative time, postoperative complications or blood
      loss. No cervical hematomas developed in group A. No patients needed to be
      readmitted because of major complications relating to the carotid endarterectomy.
      During the video-communication, 28 patients (31%) with a hypertensive crisis were
      treated by administration of amlodipine. At discharge, a questionnaire showed
      that there was a feeling of insecurity in both groups: 87% in group A vs. 79% in
      group B (P > 0.05). In group A, insecurity decreased after the first video
      connection and disappeared after the 8th day postoperatively. Telemedicine
      appears feasible and useful in carotid endarterectomy and may have other
      applications in vascular surgery care.

PMID- 20679408
TI  - A comparison of oral and written english styles in african american students at
      different stages of writing development.
AB  - PURPOSE: The purpose of this investigation was to compare the rates of using
      African American English (AAE) grammatical features in spoken and written
      language at different points in literacy development. Based on Kroll's model
      (1981), a high degree of similarity in use between the modalities was expected at
      Grade 3, and lower similarity was expected at Grade 8. METHOD: Spoken and written
      language samples were analyzed for the occurrence of 6 AAE morphosyntactic
      features. Fifteen third graders and 15 eighth graders were asked to respond to
      interview questions and to retell stories in both modalities. Percentage use of
      the AAE grammatical features and a dialectal density measure were used to measure
      rates of AAE occurrence. RESULTS: Findings indicated comparable use of dialect in
      spoken and written modalities for 3(rd) graders, but a difference in use between
      the modalities for 8(th) graders. The 8(th) graders used more dialectal features
      in speaking than writing. CONCLUSION: These results suggest that there is likely
      a period in writing development when speakers of AAE learn to dialect switch in
      their writing.

PMID- 20679409
TI  - Testing and beyond: strategies and tools for evaluating and assessing infants and
      toddlers.
AB  - PURPOSE: This article is a condensation of the recent American Speech-Language
      Hearing Association (ASHA) document entitled Roles and Responsibilities of Speech
      Language Pathologists in Early Intervention: Guidelines (ASHA, 2008). The article
      presents information on recommended and evidence-based practices related to the
      screening, evaluation, and assessment of infants and toddlers with, or at risk
      for, communication deficits. It is intended to be used by clinicians to enhance
      their practices. METHOD: The Guidelines document was developed using the
      available research evidence, expert clinical perspectives, and, when possible,
      family perspectives related to the screening, evaluation, and assessment process.
      The current article includes key definitions and an overview of recommended
      practices in screening, evaluation, assessment, and results interpretation.
      IMPLICATIONS: The article provides important and timely information for
      professionals and families related to the screening, evaluation, and assessment
      of infants and toddlers with, or at risk for, communication deficits. Speech
      language pathologists, other professionals, and family members can use the
      information to implement recommended and evidence-based practices when screening,
      evaluating, and assessing young children for communication deficits.

PMID- 20679411
TI  - Written language disorders: speech-language pathologists' training, knowledge,
      and confidence.
AB  - PURPOSE: This study examined speech-language pathologists' (SLPs') perceptions of
      their (a) educational and clinical training in evaluating and treating written
      language disorders, (b) knowledge bases in this area, (c) sources of knowledge
      about written language disorders, (d) confidence levels, and (e) predictors of
      confidence in working with written language disorders. METHOD: A 6-part survey
      was developed and was mailed to 1,000 school-based SLPs. RESULTS: SLPs (n = 599)
      practicing in 47 states responded to the survey. A majority (60.3%) reported
      working with a child with a written language disorder either weekly or daily.
      SLPs described their educational and clinical training as "limited" in the
      evaluation and treatment of children with written language disorders. The average
      SLP stated feeling "somewhat confident" to evaluate and treat written language
      disorders, and 63.8% reported that they received most of their knowledge through
      "on-the job" training. Confidence was related to four variables: on-the-job
      training, general knowledge about written language disorders, attendance at
      conventions, and understanding of collaborative efforts. CONCLUSION: Our findings
      provide information about SLPs' training, knowledge, and confidence about written
      language beyond anecdotal reports and fill research gaps regarding SLPs'
      preservice and professional development needs. Predictors of confidence are
      discussed.

PMID- 20679410
TI  - Knowledge of mathematical equivalence in children with specific language
      impairment: insights from gesture and speech.
AB  - PURPOSE: This study investigated understanding of mathematical equivalence in
      children with and without specific language impairment (SLI). METHOD: A total of
      34 children (ages 8;1 [years;months] to 11;7), including 9 with expressive SLI (E
      SLI), 8 with expressive and receptive SLI (ER-SLI), and 17 age-matched typically
      developing (TD) children completed addition and mathematical equivalence
      problems. The problem-solving strategies revealed in solutions and in gestural
      and verbal explanations were coded. RESULTS: The children with SLI were less
      accurate than their TD peers in solving addition and equivalence problems. None
      of the children in the ER-SLI group solved the equivalence problems correctly;
      however, the number of children who solved any of the equivalence problems
      correctly did not differ in the E-SLI and CA groups. Children in the ER-SLI group
      tended to express incorrect strategies for solving the equivalence problems in
      both gesture and speech, whereas children in the E-SLI group often expressed
      correct strategies in gestures, but incorrect strategies in speech. CONCLUSION:
      Children with SLI showed delays in their knowledge of mathematical equivalence.
      Children with ER-SLI displayed greater delays than children with E-SLI. Children
      with E-SLI sometimes expressed more advanced knowledge in gestures, suggesting
      that their knowledge is represented in a nonverbal format.

PMID- 20679413
TI  - Close relationships in adolescents with and without a history of specific
      language impairment.
AB  - PURPOSE: Engagement in close friendships and romantic relationships becomes
      particularly salient in adolescence. This study examined the influence of
      language, behavioral, and social variables on the level of emotional engagement
      experienced by adolescents with and without a history of specific language
      impairment (SLI). METHOD: Ninety adolescents with SLI and 91 adolescents with
      typical language abilities (TD) completed two assessment sessions between the
      ages of 16 and 17. RESULTS: The group with SLI had significantly lower emotional
      engagement scores than the TD group. Some 24% of adolescents with a history of
      SLI were judged to have poor emotional engagement in close relationships,
      compared to only 2% of the TD adolescents. A regression analysis found that
      language ability, prosocial behavior, and shyness were concurrently predictive of
      level of emotional engagement in close relationships. CONCLUSION: Some
      adolescents with SLI may be less emotionally engaged in their close relationships
      than their TD peers.

PMID- 20679414
TI  - Retraction. Calcium-dependent platelet aggregation through the interaction
      between phosphatidylserine and LOX-1.

PMID- 20679415
TI  - Mitochondrial reprogramming through cardiac oxygen sensors in ischaemic heart
      disease.
AB  - Under hypoxic conditions, mitochondria can represent a threat to the cell because
      of their capacity to generate toxic reactive oxygen species (ROS). However,
      cardiomyocytes are equipped with an oxygen-sensing pathway that involves prolyl
      hydroxylase oxygen sensors and hypoxia-inducible factors (HIFs), which induces a
      tightly regulated programme to keep ischaemic mitochondrial activity under
      control. The aim of this review is to provide an update on the pathways leading
      to mitochondrial reprogramming, which occurs in the myocardium during ischaemia,
      with particular emphasis on those induced by HIF activation. We start by studying
      the mechanisms of mitochondrial damage during ischaemia and upon reperfusion,
      highlighting the importance of the formation of the mitochondrial permeability
      transition pore during reperfusion and its consequences for cardiomyocyte
      survival. Next, we analyse hypoxia-induced metabolic reprogramming through HIF
      and its important consequences for mitochondrial bioenergetics, as well as the
      phenomenon known as the hibernating myocardium. Subsequently, we examine the
      mechanisms underlying ischaemic preconditioning, focusing, in particular, on
      those that involve the HIF pathway, such as adenosine signalling, sub-lethal ROS
      generation, and nitric oxide production. Finally, the role of the mitochondrial
      uncoupling proteins in ischaemia tolerance is discussed.

PMID- 20679416
TI  - A novel chimeric natriuretic peptide reduces cardiomyocyte hypertrophy through
      the NHE-1-calcineurin pathway.
AB  - AIMS: Natriuretic peptides (NPs) inhibit cardiomyocyte hypertrophy through a
      cyclic GMP (cGMP)-dependent process, although these effects are associated with
      substantial vasodilatation. In this study, we used CU-NP, a non-vasodilatating
      novel NP synthesized from the ring structure of human C-type NP (CNP) and both C-
      and N-termini of urodilatin, and investigated whether it can directly modulate
      cardiomyocyte hypertrophy. METHODS AND RESULTS: Experiments were carried out in
      cultured neonatal rat ventricular myocytes exposed to phenylephrine, angiotensin
      II, or endothelin-1 in the absence or presence of CU-NP. CU-NP produced a
      concentration- and time-dependent increase in intracellular cGMP levels. The
      hypertrophic responses to all agonists were abrogated by 10 nM CU-NP. CU-NP
      treatment also prevented increased activity, gene and protein expression of
      sodium-hydrogen exchanger-1 (NHE-1) as well as elevations in intracellular Na(+)
      concentrations caused by hypertrophic agents. In addition, these effects were
      associated with a more than two-fold increase in activity of the Ca(2+)-dependent
      protein phosphatase calcineurin that peaked 6 h after addition of hypertrophic
      stimuli. Early (1-3 h) calcineurin activation was unaffected by CU-NP, although
      activation at 6 and 24 h was prevented by CU-NP as was the resultant
      translocation of the transcriptional factor NFAT into nuclei. CONCLUSION: Our
      study demonstrates a direct anti-hypertrophic effect of the chimeric peptide CU
      NP via NHE-1 inhibition, thereby preventing calcineurin activation and NFAT
      nuclear import. Thus, CU-NP represents a novel fusion peptide of CNP and
      urodilatin that has the potential to be developed into a therapeutic agent to
      treat cardiac hypertrophy and heart failure.

PMID- 20679417
TI  - The impact of tobacco control policies in Albania.
AB  - OBJECTIVE: To assess the impact of a tobacco control law adopted in Albania in
      2007 and to estimate the share of illicit cigarettes on the market. DESIGN:
      Comparative analysis of two waves of a nationally representative household
      survey, one conducted before the new law went into effect and the other after 2
      years. Official sales data were contrasted with the consumption estimate based on
      the survey. MAIN OUTCOME MEASURES: Smoking prevalence, quit attempts, exposure to
      cigarette advertising, exposure to second-hand smoke, total cigarette
      consumption, share of illicit packs among packs possessed by smokers. RESULTS:
      Despite the adoption of strong smoke-free policies and adverting restrictions,
      smoking prevalence in Albania has risen. The increase in prevalence has been
      driven by higher smoking rates among females (18.9% in 2007 vs 29.3% in 2009) and
      young adults (23.2% in 2007 vs 38.5% in 2009 among 18-19 year olds). Self
      reported exposure to second-hand smoke and cigarette advertising have been
      reduced since 2007. The majority of respondents are still exposed to second-hand
      smoke and more than half are exposed to tobacco advertising. Nevertheless, there
      are signs that the consumption of illicit cigarettes is declining. CONCLUSIONS:
      The impacts of smoke-free policies and an advertising ban have been limited due
      to lack of enforcement and failure to adopt a comprehensive set of tobacco
      control measures. These measures should include sizeable and regular tobacco tax
      increases in excess of the general level of inflation and income growth. The
      decline in the share of illicit cigarettes should improve the effectiveness of
      the cigarette tax policy.

PMID- 20679418
TI  - Evaluating social and behavioural impacts of English smoke-free legislation in
      different ethnic and age groups: implications for reducing smoking-related health
      inequalities.
AB  - OBJECTIVE: To explore social and behavioural impacts of English smoke-free
      legislation (SFL) in different ethnic groups. DESIGN: A longitudinal, qualitative
      panel study of smokers using in-depth interviews conducted before and after
      introduction of SFL. PARTICIPANTS: A purposive sample of 32 smokers selected from
      three ethnic groups in deprived London neighbourhoods with approximately equal
      numbers of younger and older, male and female respondents. RESULTS: SFL has had
      positive impacts with half smoking less and three quitting. Although there were
      no apparent differences in smoking and quitting behaviours between groups, there
      were notable differences in the social impacts of SFL. The greatest negative
      impacts were in smokers over 60 years, potentially increasing their social
      isolation, and on young Somali women whose smoking was driven more underground.
      In contrast, most other young adult smokers felt relatively unaffected by SFL,
      describing unexpected social benefits. Although there was high compliance,
      reports of illegal smoking were more frequent among young, ethnic minority
      smokers, with descriptions of venues involved suggesting they are ethnically
      distinct and well hidden. Half of respondents reported stopping smoking in their
      own homes after SFL, but almost all were Somali or Turkish. White respondents
      tended to report increases in home smoking. DISCUSSION: Although our study
      suggests that SFL can lead to reductions in tobacco consumption, it also shows
      that impacts vary by ethnicity, age and sex. This study highlights the importance
      of understanding the meaning of smoking in different social contexts so future
      tobacco control interventions can be developed to reduce health and social
      inequalities.

PMID- 20679419
TI  - Monepantel allosterically activates DEG-3/DES-2 channels of the gastrointestinal
      nematode Haemonchus contortus.
AB  - Monepantel is the first drug of a new family of anthelmintics, the amino
      acetonitrile derivatives (AAD), presently used to treat ruminants infected with
      gastrointestinal nematodes such as Haemonchus contortus. Monepantel shows an
      excellent tolerability in mammals and is active against multidrug-resistant
      parasites, indicating that its molecular target is absent or inaccessible in the
      host and is different from those of the classic anthelmintics. Genetic approaches
      with mutant nematodes have suggested acetylcholine receptors of the DEG-3
      subfamily as the targets of AADs, an enigmatic clade of ligand-gated ion channels
      that is specific to nematodes and does not occur in mammals. Here we demonstrate
      direct interaction of monepantel, its major active metabolite monepantel sulfone,
      and other AADs with potential targets of the DEG-3 subfamily of acetylcholine
      receptors. H. contortus DEG-3/DES-2 receptors were functionally expressed in
      Xenopus laevis oocytes and were found to be preferentially activated by choline,
      to permeate monovalent cations, and to a smaller extent, calcium ions. Although
      monepantel and monepantel sulfone did not activate the channels by themselves,
      they substantially enhanced the late currents after activation of the channels
      with choline, indicating that these AADs are type II positive allosteric
      modulators of H. contortus DEG-3/DES-2 channels. It is noteworthy that the R
      enantiomer of monepantel, which is inactive as an anthelmintic, inhibited the
      late currents after stimulation of H. contortus DEG-3/DES-2 receptors with
      choline. In summary, we present the first direct evidence for interaction of AADs
      with DEG-3-type acetylcholine receptors and discuss these findings in the context
      of anthelmintic action of AADs.

PMID- 20679420
TI  - Tag rugby: a safe alternative? A review of hand injuries sustained playing tag
      rugby (2007 season).
AB  - INTRODUCTION: Tag rugby is a non-contact, seven-a-side, team sport in which each
      player wears specially designed shorts with velcro 'tags' attached to them. While
      tag rugby is a relatively new sport it has grown rapidly in popularity. As a
      result of its increasing popularity an increased frequency of attendances at
      plastic surgery clinics was observed and it was decided a review of all hand
      injuries associated with this new sport was required. MATERIALS AND METHODS: A
      retrospective case note review of all hand injuries occurring during the tag
      rugby season for 2007 (March-August) was conducted, with any tag rugby-related
      hand injuries being selected for further examination. RESULTS: Tag rugby, while
      being a non-contact sport, is certainly not without a definite injury risk with
      12 patients having single digit injuries, ranging from tendon avulsions to
      phalangeal fractures. The mean age of the injured patients was 26.8 years.
      DISCUSSION: All of the hand injuries were sustained while 'tackling' during
      regular play, the hand injuries sustained were all treated using well-described
      methods and all the patients are recovering well. While the risk of a severe,
      life-threatening injury is unlikely while playing tag rugby, there is a real risk
      of sustaining a potentially debilitating hand injury.

PMID- 20679421
TI  - Successful sonographic visualisation of the abdominal aorta differs significantly
      among a diverse group of credentialed emergency department providers.
AB  - BACKGROUND: The aims of this study were to examine the association between
      emergency department (ED) providers' experience with bedside ultrasound after
      achieving credentialing for abdominal aortic aneurysm (AAA) sonography, and their
      successful visualisation rate of the abdominal aorta among consecutive patients
      who presented asymptomatically but with risk factors for AAA. METHODS: Study
      coordinators enrolled asymptomatic men > 50 years presenting to a single ED with
      AAA risk factors. One of 20 AAA credentialed ED sonographers screened each
      subject for AAA. Screening forms and ultrasound images were reviewed for quality
      assurance. Multivariate logistic regression was used to estimate OR of
      visualisation and correct measurement among providers with varying experience,
      adjusted for bowel gas and body mass index (BMI). RESULTS: During the 12 week
      enrolment, 278 patients were eligible and 196 (70%) enrolled. ED sonographers
      accurately visualised the entire abdominal aorta of 140 subjects (71.4%), did not
      completely visualise 40 (20.4%) and incorrectly measured 16 (8.2%). After
      controlling for bowel gas and BMI, providers with < 1 year of experience (OR 6.7,
      95% CI 2.0 to 22.2) and with 1-3 years experience post credentialing for AAA (OR
      9.6, 95% CI 2.2 to 43.2) were significantly less likely to visualise and
      accurately measure the aorta compared to providers with >3 years experience.
      CONCLUSION: AAA sonography performance varied markedly among a diverse group of
      already credential ED sonographers. The most experienced providers demonstrated
      best performance. The present results suggest that some providers might require >
      25 proctored scans to ensure competency and training, and training on technically
      difficult patients should be part of the credentialing process.

PMID- 20679422
TI  - Is it the H or the EMS in HEMS that has an impact on trauma patient mortality? A
      systematic review of the evidence.
AB  - BACKGROUND AND AIM: Prehospital care of trauma patients is a matter of great
      debate. The optimal transport method remains undecided, with conflicting data
      comparing helicopter and ground emergency medical transfer. This study
      systematically reviews the evidence comparing helicopter and ground transfer of
      trauma patients from the scene of injury. METHODS: A systematic literature review
      of all population-based studies evaluating the impact on mortality of helicopter
      transfer of trauma patients from the scene of injury. We searched MEDLINE, CINAHL
      and EMBASE from January 1980 to December 2008 and selected and reviewed
      potentially relevant studies. RESULTS: A search of the literature revealed 23
      eligible studies. 14 of these studies demonstrated a significant improvement in
      trauma patient mortality when transported by helicopter from the scene. 5 of the
      23 studies were of level II evidence with the remainder being of level III
      evidence. Data were then entered into an evidence table and reference made to
      transport staffing, intubation rate, time at scene and time/distance of transfer.
      CONCLUSIONS: The role and structure of HEMS in a modern trauma service is a
      debate that is likely to continue. Prehospital care design should be specific to
      critical incident frequency, geographical arrangements of hospital facilities and
      travel times within each trauma network. It is also important to consider the
      benefits and capabilities of the emergency medical team separately from the
      transport method being considered. An effective helicopter EMS will ultimately
      depend on effective operating procedures and tasking protocols, clinical
      governance, and auditing of the helicopter EMS activity.

PMID- 20679423
TI  - Pain assessments at triage with the Manchester triage system: a prospective
      observational study.
AB  - OBJECTIVE: Pain is one of the six general discriminators of the Manchester triage
      system (MTS). The frequency of pain assessments conducted at triage with the MTS,
      and patient, nurse and triage characteristics associated with pain assessments
      were studied. Also, nurses' reasons for not assessing pain at triage were
      studied. METHODS: The study consisted of two parts. In part 1, nurses from two
      emergency departments (ED) registered patient characteristics and the process of
      triage for every presenting patient during 1&emsp14;week in May 2009. The
      characteristics of triage nurses were registered on a second form. In part 2 of
      the study, 13 nurses were interviewed about reasons for not assessing pain at
      triage. RESULTS: According to the MTS guidelines, pain assessments should have
      been conducted in 86.1% of the patient presentations. It was only assessed in
      32.2% of these patients. Characteristics associated with conducting pain
      assessments were children under 12&emsp14;years of age, patients referred by
      others than a general practitioner or ambulance service, intake of medication
      before an ED visit, experience of the nurse with the MTS and the duration of
      triage. Reasons for not assessing pain according to the guidelines included the
      thought of triage nurses that pain assessments result in overtriage. CONCLUSIONS:
      Pain assessments at triage are conducted infrequently because of insufficient
      education, conducting activities at triage that are not necessary for estimating
      urgency and a lack of clarity in the MTS guidelines. Changes in these areas are
      necessary to improve the reliability and validity of pain assessments and the
      MTS.

PMID- 20679424
TI  - Response time of the Beijing 120 emergency medical service.
AB  - BACKGROUND: To assess the response time and the details of the operating
      procedure of the Beijing 120 Emergency Medical Service (EMS). METHODS: Between
      June and December 2005, 51 918 EMS cases recorded in the Dispatch Center of the
      Beijing Emergency Medical Center were analysed. RESULTS: The median response time
      of the 51 918 cases was 16.5 min; the cumulative proportions were 2.28%, 9.64%
      and 18.04% for less than 5 min, 8 min and 10 min of response time respectively,
      whereas the proportion was 19.20% for more than 30 min of response time.
      CONCLUSIONS: On the basis of this analysis, the response time of the Beijing 120
      EMS system was found to be longer than that indicated by the national standards.

PMID- 20679425
TI  - Out-of-hospital cardiac arrest (OHCA) survival in rural Northwest Ireland: 17
      years' experience.
AB  - SAVES, the name used to describe a register of survivors of out-of-hospital
      cardiac arrest (OHCA), was established in rural Northwest Ireland in 1992. From
      1992 to 2008, 80 survivors were identified (population 239,000 (2006)). Most
      incidents were witnessed (69/70) and all were in shockable rhythm at the time of
      first rhythm analysis (66/66). Of 66 patients who could be traced, 46 were alive
      in December 2008. Average survival rates appeared to increase over the lifetime
      of the database. SAVES has also contributed to the development of a national OHCA
      register.

PMID- 20679426
TI  - Survival after cardiac arrest and severe lactic acidosis (pH 6.61) due to
      haemorrhage.
AB  - This paper describes a 21-year-old man who presented to the emergency department
      with a knife wound to his buttock. He had a witnessed cardiac arrest with
      pulseless electrical activity in hospital as a result of further haemorrhage. His
      post-resuscitation arterial blood gas revealed a severe lactic acidosis (pH 6.61,
      lactate 22.0 mmol/l). Despite poor expectations he went on to make a full
      neurological recovery. To the authors' knowledge, he had the fourth-lowest pH for
      a cardiac arrest survivor with normal neurology. Severe lactic acidosis occurs
      post cardiac arrest due to imbalance between cellular oxygen supply and demand.
      Severe lactic acidosis is associated with hypoxic brain injury but has a low
      specificity in its prediction. The case illustrates that, especially in younger
      adults, severe lactic acidosis may be a poor predictor of outcome if it reflects
      a period of relative hypoperfusion preceding cardiac arrest.

PMID- 20679427
TI  - Propofol is not safe for sedation for hip relocation.

PMID- 20679428
TI  - A prehospital paediatric tension viscerothorax presenting as a tension
      pneumothorax: a diagnostic dilemma.
AB  - This article reports a case of a paediatric pre-hospital tension viscerothorax,
      and it subsequent management. It also discusses the difficulty in diagnosing this
      condition in the pre-hospital arena.

PMID- 20679429
TI  - Epidemiology of prehospital pain: an opportunity for improvement.
AB  - This retrospective, electronic patient care record review examined a consecutive
      sample of patients presenting with pain to the metropolitan region of Ambulance
      Victoria over a period of 12&emsp14;months in 2008. The majority of patients did
      not achieve clinically significant pain reduction, but did achieve some pain
      relief while in ambulance care. Those with the most severe pain had pain
      reduction that was clinically significant. Further research is needed to provide
      optimal pain relief in the prehospital setting.

PMID- 20679430
TI  - Gamma-tubulin regulates the anaphase-promoting complex/cyclosome during
      interphase.
AB  - A cold-sensitive gamma-tubulin allele of Aspergillus nidulans, mipAD159, causes
      defects in mitotic and cell cycle regulation at restrictive temperatures that are
      apparently independent of microtubule nucleation defects. Time-lapse microscopy
      of fluorescently tagged mitotic regulatory proteins reveals that cyclin B, cyclin
      dependent kinase 1, and the Ancdc14 phosphatase fail to accumulate in a subset of
      nuclei at restrictive temperatures. These nuclei are permanently removed from the
      cell cycle, whereas other nuclei, in the same multinucleate cell, cycle normally,
      accumulating and degrading these proteins. After each mitosis, additional
      daughter nuclei fail to accumulate these proteins, resulting in an increase in
      noncycling nuclei over time and consequent inhibition of growth. Extensive
      analyses reveal that these noncycling nuclei result from a nuclear autonomous,
      microtubule-independent failure of inactivation of the anaphase-promoting
      complex/cyclosome. Thus, gamma-tubulin functions to regulate this key mitotic and
      cell cycle regulatory complex.

PMID- 20679431
TI  - The inositol 5-phosphatase SHIP2 regulates endocytic clathrin-coated pit
      dynamics.
AB  - Phosphatidylinositol (PI) 4,5-bisphosphate (PI(4,5)P(2)) and its phosphorylated
      product PI 3,4,5-triphosphate (PI(3,4,5)P(3)) are two major phosphoinositides
      concentrated at the plasma membrane. Their levels, which are tightly controlled
      by kinases, phospholipases, and phosphatases, regulate a variety of cellular
      functions, including clathrin-mediated endocytosis and receptor signaling. In
      this study, we show that the inositol 5-phosphatase SHIP2, a negative regulator
      of PI(3,4,5)P(3)-dependent signaling, also negatively regulates PI(4,5)P(2)
      levels and is concentrated at endocytic clathrin-coated pits (CCPs) via
      interactions with the scaffold protein intersectin. SHIP2 is recruited early at
      the pits and dissociates before fission. Both knockdown of SHIP2 expression and
      acute production of PI(3,4,5)P(3) shorten CCP lifetime by enhancing the rate of
      pit maturation, which is consistent with a positive role of both SHIP2
      substrates, PI(4,5)P(2) and PI(3,4,5)P(3), on coat assembly. Because SHIP2 is a
      negative regulator of insulin signaling, our findings suggest the importance of
      the phosphoinositide metabolism at CCPs in the regulation of insulin signal
      output.

PMID- 20679432
TI  - S-glutathionylation activates STIM1 and alters mitochondrial homeostasis.
AB  - Oxidant stress influences many cellular processes, including cell growth,
      differentiation, and cell death. A well-recognized link between these processes
      and oxidant stress is via alterations in Ca(2+) signaling. However, precisely how
      oxidants influence Ca(2+) signaling remains unclear. Oxidant stress led to a
      phenotypic shift in Ca(2+) mobilization from an oscillatory to a sustained
      elevated pattern via calcium release-activated calcium (CRAC)-mediated capacitive
      Ca(2+) entry, and stromal interaction molecule 1 (STIM1)- and Orai1-deficient
      cells are resistant to oxidant stress. Functionally, oxidant-induced Ca(2+) entry
      alters mitochondrial Ca(2+) handling and bioenergetics and triggers cell death.
      STIM1 is S-glutathionylated at cysteine 56 in response to oxidant stress and
      evokes constitutive Ca(2+) entry independent of intracellular Ca(2+) stores.
      These experiments reveal that cysteine 56 is a sensor for oxidant-dependent
      activation of STIM1 and demonstrate a molecular link between oxidant stress and
      Ca(2+) signaling via the CRAC channel.

PMID- 20679433
TI  - p125A exists as part of the mammalian Sec13/Sec31 COPII subcomplex to facilitate
      ER-Golgi transport.
AB  - Coat protein II (COPII)-mediated export from the endoplasmic reticulum (ER)
      involves sequential recruitment of COPII complex components, including the Sar1
      GTPase, the Sec23/Sec24 subcomplex, and the Sec13/Sec31 subcomplex. p125A was
      originally identified as a Sec23A-interacting protein. Here we demonstrate that
      p125A also interacts with the C-terminal region of Sec31A. The Sec31A-interacting
      domain of p125A is between residues 260-600, and is therefore a distinct domain
      from that required for interaction with Sec23A. Gel filtration and
      immunodepletion studies suggest that the majority of cytosolic p125A exists as a
      ternary complex with the Sec13/Sec31A subcomplex, suggesting that Sec 13, Sec31A,
      and p125A exist in the cytosol primarily as preassembled Sec13/Sec31A/p125A
      heterohexamers. Golgi morphology and protein export from the ER were affected in
      p125A-silenced cells. Our results suggest that p125A is part of the Sec13/Sec31A
      subcomplex and facilitates ER export in mammalian cells.

PMID- 20679434
TI  - Akt/PKB suppresses DNA damage processing and checkpoint activation in late G2.
AB  - Using chemical genetics to reversibly inhibit Cdk1, we find that cells arrested
      in late G2 are unable to delay mitotic entry after irradiation. Late G2 cells
      detect DNA damage lesions and form gamma-H2AX foci but fail to activate Chk1.
      This reflects a lack of DNA double-strand break processing because late G2 cells
      fail to recruit RPA (replication protein A), ATR (ataxia telangiectasia and Rad3
      related), Rad51, or CtIP (C-terminal interacting protein) to sites of radiation
      induced damage, events essential for both checkpoint activation and initiation of
      DNA repair by homologous recombination. Remarkably, inhibition of Akt/PKB
      (protein kinase B) restores DNA damage processing and Chk1 activation after
      irradiation in late G2. These data demonstrate a previously unrecognized role for
      Akt in cell cycle regulation of DNA repair and checkpoint activation. Because
      Akt/PKB is frequently activated in many tumor types, these findings have
      important implications for the evolution and therapy of such cancers.

PMID- 20679435
TI  - Ephexin4 and EphA2 mediate cell migration through a RhoG-dependent mechanism.
AB  - EphA2, a member of the Eph receptor family, is frequently overexpressed in a
      variety of human cancers, including breast cancers, and promotes cancer cell
      motility and invasion independently of its ligand ephrin stimulation. In this
      study, we identify Ephexin4 as a guanine nucleotide exchange factor (GEF) for
      RhoG that interacts with EphA2 in breast cancer cells, and knockdown and rescue
      experiments show that Ephexin4 acts downstream of EphA2 to promote ligand
      independent breast cancer cell migration and invasion toward epidermal growth
      factor through activation of RhoG. The activation of RhoG recruits its effector
      ELMO2 and a Rac GEF Dock4 to form a complex with EphA2 at the tips of cortactin
      rich protrusions in migrating breast cancer cells. In addition, the Dock4
      mediated Rac activation is required for breast cancer cell migration. Our
      findings reveal a novel link between EphA2 and Rac activation that contributes to
      the cell motility and invasiveness of breast cancer cells.

PMID- 20679436
TI  - The EspF effector, a bacterial pathogen's Swiss army knife.
AB  - Central to the pathogenesis of many bacterial pathogens is the ability to deliver
      effector proteins directly into the cells of their eukaryotic host. EspF is one
      of many effector proteins exclusive to the attaching and effacing pathogen family
      that includes enteropathogenic (EPEC) and enterohemorrhagic (EHEC) Escherichia
      coli. Work in recent years has revealed EspF to be one of the most
      multifunctional effector proteins known, with defined roles in several host
      cellular processes, including disruption of the epithelial barrier,
      antiphagocytosis, microvillus effacement, host membrane remodelling, modulation
      of the cytoskeleton, targeting and disruption of the nucleolus, intermediate
      filament disruption, cell invasion, mitochondrial dysfunction, apoptosis, and
      inhibition of several important epithelial transporters. Surprisingly, despite
      this high number of functions, EspF is a relatively small effector protein, and
      recent work has begun to decipher the molecular events that underlie its
      multifunctionality. This review focuses on the activities of EspF within the host
      cell and discusses recent findings and molecular insights relating to the
      virulence functions of this fascinating bacterial effector.

PMID- 20679437
TI  - Overcoming the heme paradox: heme toxicity and tolerance in bacterial pathogens.
AB  - Virtually all bacterial pathogens require iron to infect vertebrates. The most
      abundant source of iron within vertebrates is in the form of heme as a cofactor
      of hemoproteins. Many bacterial pathogens have elegant systems dedicated to the
      acquisition of heme from host hemoproteins. Once internalized, heme is either
      degraded to release free iron or used intact as a cofactor in catalases,
      cytochromes, and other bacterial hemoproteins. Paradoxically, the high redox
      potential of heme makes it a liability, as heme is toxic at high concentrations.
      Although a variety of mechanisms have been proposed to explain heme toxicity, the
      mechanisms by which heme kills bacteria are not well understood. Nonetheless,
      bacteria employ various strategies to protect against and eliminate heme
      toxicity. Factors involved in heme acquisition and detoxification have been found
      to contribute to virulence, underscoring the physiological relevance of heme
      stress during pathogenesis. Herein we describe the current understanding of the
      mechanisms of heme toxicity and how bacterial pathogens overcome the heme paradox
      during infection.

PMID- 20679438
TI  - Mycobacterium bovis BCG-specific Th17 cells confer partial protection against
      Mycobacterium tuberculosis infection in the absence of gamma interferon.
AB  - Protective immunity against tuberculosis (TB) requires the integrated response of
      a network of lymphocytes. Both gamma interferon (IFN-gamma)- and interleukin 17
      (IL-17)-secreting CD4(+) T cells have been identified in subjects with latent TB
      infection and during experimental Mycobacterium tuberculosis infection, but the
      contribution of Th17 cells to protective immunity is unclear. To examine their
      protective effects in vivo, we transferred mycobacterium-specific IL-17- and IFN
      gamma-secreting CD4(+) T cells isolated from M. tuberculosis BCG-immunized IL
      12p40(-/-) and IFN-gamma(-/-) or wild-type mice, respectively, into M.
      tuberculosis-infected IL-12p40(-/-) or RAG(-/-) mice. In the absence of IL-12 and
      IL-23, neither IL-17-secreting (Th17) nor IFN-gamma-secreting (Th1) BCG-specific
      T cells expanded or provided protection against M. tuberculosis. In RAG(-/-)
      recipients with an intact IL-12/IL-23 axis, both Th17 and Th1 cells were
      activated and induced significant protection against M. tuberculosis. The
      reduction in the bacterial load following transfer of IFN-gamma(-/-) Th17 cells
      was associated with significant prolongation of survival compared to recipients
      of naive IFN-gamma(-/-) T cells. This effect was at the cost of an increased
      inflammatory infiltrate characterized by an excess of neutrophils. Therefore,
      Th17 cells can provide IFN-gamma-independent protection against M. tuberculosis,
      and this effect may contribute to the early control of M. tuberculosis infection.

PMID- 20679439
TI  - Mucosal immunization with Vibrio cholerae outer membrane vesicles provides
      maternal protection mediated by antilipopolysaccharide antibodies that inhibit
      bacterial motility.
AB  - Vibrio cholerae is the causative agent of cholera, a severe diarrheal disease
      that remains endemic in many parts of the world and can cause outbreaks wherever
      sanitation and clean water systems break down. Prevention of disease could be
      achieved through improved sanitation and clean water provision supported by
      vaccination. V. cholerae serogroup O1 is the major cause of cholera; O1 serotypes
      Inaba and Ogawa have similar disease burdens, while O139 is the only non-O1
      serogroup to cause epidemics. We showed previously that immunization of adult
      female mice with purified V. cholerae outer membrane vesicles (OMVs) elicits an
      antibody response that protect neonates from oral V. cholerae challenge and that
      suckling from an immunized dam accounts for the majority of protection from V.
      cholerae colonization. Here we report that lipopolysaccharide (LPS) is the major
      OMV protective antigen. Mucosal immunization with OMVs from Inaba or Ogawa
      provides significant cross-serotype protection from V. cholerae colonization,
      although serotype-specific antigens are dominant. OMVs from O1 or O139 do not
      provide cross-serogroup protection, but by immunization with a mixture of O1 and
      O139 OMVs, cross-serogroup protection was achieved. Neonatal protection is not
      associated with significant bacterial death but may involve inhibition of
      motility, as antibodies from OMV-immunized mice inhibit V. cholerae motility in
      vitro, with trends that parallel in vivo protection. Motility assays also reveal
      that a higher antibody titer is required to immobilize O139 compared to O1, a
      phenotype that is O139 capsule dependent.

PMID- 20679440
TI  - Limited role of secreted aspartyl proteinases Sap1 to Sap6 in Candida albicans
      virulence and host immune response in murine hematogenously disseminated
      candidiasis.
AB  - Candida albicans secreted aspartyl proteinases (Saps) are considered virulence
      associated factors. Several members of the Sap family were claimed to play a
      significant role in the progression of candidiasis established by the
      hematogenous route. This assumption was based on the observed attenuated
      virulence of sap-null mutant strains. However, the exclusive contribution of SAP
      genes to their attenuated phenotype was not unequivocally confirmed, as the Ura
      status of these mutant strains could also have contributed to the attenuation. In
      this study, we have reassessed the importance of SAP1 to SAP6 in a murine model
      of hematogenously disseminated candidiasis using sap-null mutant strains not
      affected in their URA3 gene expression and compared their virulence phenotypes
      with those of Ura-blaster sap mutants. The median survival time of BALB/c mice
      intravenously infected with a mutant strain lacking SAP1 to SAP3 was equivalent
      to that of mice infected with wild-type strain SC5314, while those infected with
      mutant strains lacking SAP5 showed slightly extended survival times.
      Nevertheless, no differences could be observed between the wild type and a
      Deltasap456 mutant in their abilities to invade mouse kidneys. Likewise, a
      deficiency in SAP4 to SAP6 had no noticeable impact on the immune response
      elicited in the spleens and kidneys of C. albicans-infected mice. These results
      contrast with the behavior of equivalent Ura-blaster mutants, which presented a
      significant reduction in virulence. Our results suggest that Sap1 to Sap6 do not
      play a significant role in C. albicans virulence in a murine model of
      hematogenously disseminated candidiasis and that, in this model, Sap1 to Sap3 are
      not necessary for successful C. albicans infection.

PMID- 20679441
TI  - Identification of the TcpP-binding site in the toxT promoter of Vibrio cholerae
      and the role of ToxR in TcpP-mediated activation.
AB  - ToxR-dependent recruitment of TcpP to the toxT promoter facilitates toxT
      transcription in Vibrio cholerae, initiating a regulatory cascade that culminates
      in cholera toxin expression and secretion. Although TcpP usually requires ToxR to
      activate the toxT promoter, TcpP overexpression can circumvent the requirement
      for ToxR in this process. To define nucleotides critical for TcpP-dependent
      promoter recognition and activation, a series of toxT promoter derivatives with
      single-base-pair transversions spanning the TcpP-binding site were generated and
      used as plasmid-borne toxT-lacZ fusions, as DNA mobility shift targets, and as
      allelic replacements of the chromosomal toxT promoter. When present in DeltatoxR
      V. cholerae overexpressing TcpP, several transversions affecting nucleotides
      within two direct repeats present in the TcpP-binding region (TGTAA-N(6)-TGTAA)
      caused defects in TcpP-dependent toxT-lacZ fusion activation and toxin
      production. Electrophoretic mobility shift assays demonstrated that these same
      transversions reduced the affinity of the toxT promoter for TcpP. The presence of
      ToxR suppressed transcription activation defects associated with most, but not
      all, transversions. Particularly, the central thymine nucleotide of both
      pentameric repeats was essential for efficient toxT activation, even in the
      presence of ToxR. These results suggest that the toxT promoter recognition
      function provided by ToxR can facilitate the interaction of TcpP with the toxT
      promoter but is insufficient for promoter activation when the TcpP-binding site
      has been severely compromised by mutation. Thus, the interaction of TcpP with
      nucleotides of the direct repeat sequences appears to be a prerequisite for toxT
      promoter activation.

PMID- 20679442
TI  - Impaired immune tolerance to Porphyromonas gingivalis lipopolysaccharide promotes
      neutrophil migration and decreased apoptosis.
AB  - Periodontitis, a chronic inflammatory disease of the tissues supporting the
      teeth, is characterized by an exaggerated host immune and inflammatory response
      to periopathogenic bacteria. Toll-like receptor activation, cytokine network
      induction, and accumulation of neutrophils at the site of inflammation are
      important in the host defense against infection. At the same time, induction of
      immune tolerance and the clearance of neutrophils from the site of infection are
      essential in the control of the immune response, resolution of inflammation, and
      prevention of tissue destruction. Using a human monocytic cell line, we
      demonstrate that Porphyromonas gingivalis lipopolysaccharide (LPS), which is a
      major etiological factor in periodontal disease, induces only partial immune
      tolerance, with continued high production of interleukin-8 (IL-8) but diminished
      secretion of tumor necrosis factor alpha (TNF-alpha) after repeated challenge.
      This cytokine response has functional consequences for other immune cells
      involved in the response to infection. Primary human neutrophils incubated with
      P. gingivalis LPS-treated naive monocyte supernatant displayed a high migration
      index and increased apoptosis. In contrast, neutrophils treated with P.
      gingivalis LPS-tolerized monocyte supernatant showed a high migration index but
      significantly decreased apoptosis. Overall, these findings suggest that induction
      of an imbalanced immune tolerance in monocytes by P. gingivalis LPS, which favors
      continued secretion of IL-8 but decreased TNF-alpha production, may be associated
      with enhanced migration of neutrophils to the site of infection but also with
      decreased apoptosis and may play a role in the chronic inflammatory state seen in
      periodontal disease.

PMID- 20679443
TI  - Role of interleukin-17A in cell-mediated protection against Staphylococcus aureus
      infection in mice immunized with the fibrinogen-binding domain of clumping factor
      A.
AB  - Clumping factor A (ClfA) is a fibrinogen-binding cell wall-attached protein and
      an important virulence factor of Staphylococcus aureus. Previous studies reported
      that an immunization with the fibrinogen-binding domain of ClfA (ClfA(40-559))
      protected animals against S. aureus infection. It was reported that some
      cytokines are involved in the pathogenesis of staphylococcal diseases and in host
      defense against S. aureus infection. However, the role of cytokines in the
      protective effect of ClfA(40-559) as a vaccine has not been elucidated. In this
      study, we demonstrated that the spleen cells of ClfA(40-559)-immunized mice
      produced a large amount of interleukin-17A (IL-17A). The protective effect of
      immunization was exerted in wild-type mice but not in IL-17A-deficient mice. IL
      17A mRNA expression was increased in the spleens and kidneys of immunized mice
      after infection. CXCL2 and CCL2 mRNA expression was increased in the spleens and
      kidneys, respectively. Consistent with upregulation of the mRNA expression,
      neutrophils infiltrated into the spleens extensively and macrophage infiltration
      was observed in the kidneys of immunized mice. These results suggest that
      immunization with ClfA(40-559) induces the IL-17A-producing cells and that IL-17
      mediated cellular immunity is involved in the protective effect induced by
      immunization with ClfA(40-559) against S. aureus infection.

PMID- 20679444
TI  - Pathogenic role of macrophages in intradermal infection of methicillin-resistant
      Staphylococcus aureus in thermally injured mice.
AB  - Intradermal infection of methicillin-resistant Staphylococcus aureus (MRSA) in
      burned mice was pathogenically analyzed. An abscess was formed in normal mice
      intradermally infected with 10(8) CFU/mouse of MRSA, and all of these mice
      survived after the infection; however, abscess formation was not demonstrated to
      occur in burned mice similarly exposed to the pathogen, and all of these mice
      died within 5 days of infection. In burned mice, MRSA infected at the burn site
      intradermal tissues spread quickly throughout the whole body, while in normal
      mice, the pathogen remained localized at the infection site. Macrophages (Mphi)
      isolated from the infection site tissues of normal mice produced interleukin-12
      (IL-12) but not IL-10 and were characterized as M1Mphi. These M1Mphi were not
      isolated from the infection site tissues of burned mice. When normal-mouse
      infection site tissue Mphi were adoptively transferred to burned mice at the MRSA
      infection site, an abscess formed, and the infection did not develop into sepsis.
      In contrast, an abscess did not form and sepsis developed in normal mice that
      were inoculated with burned-mouse infection site tissue Mphi. These Mphi produced
      IL-10 but not IL-12 and were characterized as M2Mphi. These results indicate that
      abscess formation is a major mechanism of host resistance against intradermal
      MRSA infection. M1Mphi in the tissues surrounding the infection site play a
      pivotal role in abscess formation; however, the abscess is not formed in burned
      mice where M2Mphi predominate. M2Mphi have been described as inhibitor cells for
      Mphi conversion from resident Mphi to M1Mphi.

PMID- 20679445
TI  - The Staphylococcus aureus lipoprotein SitC colocalizes with Toll-like receptor 2
      (TLR2) in murine keratinocytes and elicits intracellular TLR2 accumulation.
AB  - SitC is one of the predominant lipoproteins in Staphylococcus aureus. Recently,
      SitC was shown to be capable of stimulating Toll-like receptor 2 (TLR2), but the
      mechanism of TLR2 activation by SitC has not been analyzed in detail so far. In
      this study, we purified C-terminally His-tagged SitC (SitC-His) from
      Staphylococcus aureus. SitC-His induced interleukin-6 (IL-6) and tumor necrosis
      factor alpha (TNF-alpha) release in human monocytes and also NF-kappaB activation
      in TLR2-transfected HEK293 cells, indicating TLR2-specific activation. SitC not
      only induced a TLR2-dependent release of IL-6 in primary murine keratinocytes
      (MKs) but also induced intracellular accumulation of TLR2, which was time and
      concentration dependent. Cy2-labeled SitC-His colocalized specifically with TLR2
      in MKs and was also internalized in TLR2 knockout MKs, suggesting a TLR2
      independent uptake. Neither activation nor colocalization of SitC-His was
      observed with TLR4 or Nod2. The results show that the native lipoprotein SitC-His
      specifically colocalizes with TLR2, is internalized by host cells, induces
      proinflammatory cytokines, and triggers intracellular accumulation of TLR2.

PMID- 20679446
TI  - Three Yersinia pestis adhesins facilitate Yop delivery to eukaryotic cells and
      contribute to plague virulence.
AB  - To establish a successful infection, Yersinia pestis requires the delivery of
      cytotoxic Yops to host cells. Yops inhibit phagocytosis, block cytokine
      responses, and induce apoptosis of macrophages. The Y. pestis adhesin Ail
      facilitates Yop translocation and is required for full virulence in mice. To
      determine the contributions of other adhesins to Yop delivery, we deleted five
      known adhesins of Y. pestis. In addition to Ail, plasminogen activator (Pla) and
      pH 6 antigen (Psa) could mediate Yop translocation to host cells. The
      contribution of each adhesin to binding and Yop delivery was dependent upon the
      growth conditions. When cells were pregrown at 28 degrees C and pH 7, the order
      of importance for adhesins in cell binding and cytotoxicity was Ail > Pla > Psa.
      Y. pestis grown at 37 degrees C and pH 7 had equal contributions from Ail and Pla
      but an undetectable role for Psa. At 37 degrees C and pH 6, both Ail and Psa
      contributed to binding and Yop delivery, while Pla contributed minimally. Pla
      mediated Yop translocation was independent of protease activity. Of the three
      single mutants, the Deltaail mutant was the most defective in mouse virulence.
      The expression level of ail was also the highest of the three adhesins in
      infected mouse tissues. Compared to an ail mutant, additional deletion of psaA
      (encoding Psa) led to a 130,000-fold increase in the 50% lethal dose for mice
      relative to that of the KIM5 parental strain. Our results indicate that in
      addition to Ail, Pla and Psa can serve as environmentally specific adhesins to
      facilitate Yop secretion, a critical virulence function of Y. pestis.

PMID- 20679448
TI  - Interpretation time of computer-aided detection at screening mammography.
AB  - PURPOSE: To prospectively determine the interpretation time associated with
      computer-aided detection (CAD) and to analyze how CAD affected radiologists'
      decisions and their level of confidence in their interpretations of digital
      screening mammograms. MATERIALS AND METHODS: An Institutional Review Board
      exemption was obtained, and patient consent was waived in this HIPAA compliant
      study. The participating radiologists gave informed consent. Five radiologists
      were prospectively studied as they interpreted 267 clinical digital screening
      mammograms. Interpretation times, recall decisions, and confidence levels were
      recorded without CAD and then with CAD. Software was used for linear regression
      fitting of interpretation times. P values less than .05 were considered to
      indicate statistically significant differences. RESULTS: Mean interpretation time
      without CAD was 118 seconds +/- 4.2 (standard error of the mean). Mean time for
      reviewing CAD images was 23 seconds +/- 1.5. CAD identified additional findings
      in five cases, increased confidence in 38 cases, and decreased confidence in 21
      cases. Interpretation time without CAD increased with the number of mammographic
      views (P < .0001). Mean times for interpretation without CAD and review of the
      CAD images both increased with the number of CAD marks (P < .0001). The
      interpreting radiologist was a significant variable for all interpretation times
      (P < .0001). Interpretation time with CAD increased by 3.2 seconds (95%
      confidence interval: 1.8, 4.6) for each calcification cluster marked and by 7.3
      seconds (95% confidence interval: 4.7, 9.9) for each mass marked. CONCLUSION: The
      additional time required to review CAD images represented a 19% increase in the
      mean interpretation time without CAD. CAD requires a considerable time investment
      for digital screening mammography but may provide less measureable benefits in
      terms of confidence of the radiologists.

PMID- 20679447
TI  - Viscoelasticity-based staging of hepatic fibrosis with multifrequency MR
      elastography.
AB  - PURPOSE: To analyze the dynamics of the shear modulus of the liver to assess the
      optimal driving frequency and to determine the diagnostic accuracy of generalized
      frequency-independent elasticity cutoff values for staging hepatic fibrosis.
      MATERIALS AND METHODS: This institutional review board-approved prospective study
      included 16 healthy volunteers and 72 patients with biopsy-proved liver fibrosis.
      After obtaining written informed consent, imaging was performed at 1.5-T by using
      a motion-sensitized echo-planar imaging sequence. Wave excitation was performed
      by an actuator introducing a superposition of four frequencies (25.0, 37.5, 50.0,
      62.5 Hz) of shear waves. The elasticity u value and the structure geometry
      parameter alpha were calculated by using the two-parameter springpot model. The
      performance of magnetic resonance (MR) elastography in staging liver fibrosis was
      assessed with area under the receiver operating characteristic curve (AUROC)
      analysis and Spearman correlation analysis. RESULTS: Elasticity increased with
      stage of fibrosis, with mean values as follows: for volunteers, 2.25 kPa +/- 0.43
      (standard deviation); stage F1, 2.61 kPa +/- 0.43; stage F2, 3.00 kPa +/- 0.63;
      stage F3, 3.86 kPa +/- 0.61; and stage F4, 5.86 kPa +/- 1.22. Frequency
      independent cutoff values derived for fibrosis and AUROC values, respectively,
      were as follows: stage F1 or higher, 2.84 kPa and 0.9128; stage F2 or higher,
      3.18 kPa and 0.9244; stage F3 or higher, 3.32 kPa and 0.9744; and equivalent to
      stage F4, 4.21 kPa and 0.9931. The geometry of the tissue (alpha value) did not
      correlate with fibrosis. Frequencies of 50.0 Hz and 62.5 Hz displayed the highest
      diagnostic accuracy. CONCLUSION: The diagnostic performance of multifrequency MR
      elastography in determining the degree of hepatic fibrosis increases with stage
      of fibrosis. Metrics obtained at the higher frequencies provide better diagnostic
      performance compared with the lower frequencies. Results of the AUROC analysis
      demonstrate the high accuracy of frequency-independent cutoff values for staging
      higher grades of hepatic fibrosis.

PMID- 20679449
TI  - Evaluation of dual-energy CT for differentiating intracerebral hemorrhage from
      iodinated contrast material staining.
AB  - PURPOSE: To evaluate the efficacy of dual-energy computed tomography (CT) in the
      differentiation of intracerebral hemorrhage (ICH) from iodinated contrast
      material in patients who received contrast material via intraarterial or
      intravenous delivery. MATERIALS AND METHODS: This retrospective study was
      approved by the local institutional review board, which waived the informed
      consent requirement for the analysis. Sixteen patients with acute stroke and two
      with head trauma who had undergone intraarterial or intravenous administration of
      iodinated contrast material were evaluated by using dual-energy CT to
      differentiate areas of hyperattenuation secondary to contrast material staining
      from those representing ICH. A dual-energy CT scanner was used for imaging at 80
      and 140 kV, and a three-material decomposition algorithm was used to obtain
      virtual unenhanced images and iodine overlay images. The sensitivity,
      specificity, and accuracy of dual-energy CT in the prospective differentiation of
      intraparenchymal contrast material from hemorrhage were obtained. Follow-up
      images were used as the standard of reference. RESULTS: There were 28
      intraparenchymal areas of hyperattenuation classified at dual-energy CT as
      iodinated contrast material staining (n = 20, 71%), hemorrhage (n = 5, 18%), or
      both (n = 3, 11%). Two of the three areas of hyperattenuation seen on both
      virtual unenhanced and iodine overlay images were related to mineralization. The
      sensitivity, specificity, and accuracy of dual-energy CT in the identification of
      hemorrhage were 100% (six of six areas), 91% (20 of 22 areas), and 93% (26 of 28
      areas), respectively. CONCLUSION: Dual-energy CT can help differentiate ICH from
      iodinated contrast material staining with high sensitivity and specificity in
      patients who have recently received intraarterial or intravenous iodinated
      contrast material.

PMID- 20679450
TI  - ADEA CCI vision focuses on preparing graduates for discoveries of the future.
AB  - The vision of the American Dental Education Association's Commission on Change
      and Innovation in Dental Education (ADEA CCI) is embodied in its new slogan:
      building consensus and leading change to prepare graduates for an undiscovered
      future. The ADEA CCI envisions a future in which dental practice is vastly
      different from what it is today and dental education must be very different for
      graduates who face a future of unimaginable scientific discovery. Dental
      curricula need to change to better prepare today's dental students, not only for
      the practice of today but also for the challenges they will face in their
      practices of the future. The goal of "building consensus" is directed toward the
      many constituencies that work with dental education and its graduates. The ADEA
      CCI has developed a variety of policy recommendations, strategies, and resources
      to help policymakers, dental educators, and dental graduates better prepare for
      this undiscovered future. A key resource is twenty-two commissioned white papers
      that cover diverse topics, such as curriculum reform, facilitating change,
      faculty development, student assessment, and academic leadership.

PMID- 20679451
TI  - Dental students' knowledge about elder abuse and neglect and the reporting
      responsibilities of dentists.
AB  - Dentists are in a unique position to detect elder abuse and neglect.
      Approximately 75 percent of all physical domestic violence results in injuries to
      the head, neck, and/or mouth area, clearly visible to the dental team during
      examinations and treatment. The goal of this project was to gather a
      comprehensive understanding of predoctoral dental students' perceptions of the
      culture of abuse and neglect and their level of fluency regarding their rights
      and responsibilities as mandated reporters. This article aims to inform dental
      educators of dental students' level of awareness of elder abuse and neglect in
      order to highlight content areas to be addressed in dental school curricula and
      clinical training. A twenty-four-item survey was administered to 291 predoctoral
      dental students at the University of California, Los Angeles School of Dentistry.
      The results are organized into three general areas: prior training and education;
      perceptions of the culture of abuse and neglect; and knowledge of mandated
      reporter legal responsibilities and protections. Overall, this study found that
      most students do not feel adequately trained to report a case of elder abuse.
      Data from this study suggest that dental students need education on the
      psychosocial aspects of older adulthood, as well as training in detecting and
      reporting elder abuse.

PMID- 20679452
TI  - Rural dentists of the future: dental school enrollment strategies.
AB  - The purpose of this study was to determine the relationship, if any, of a dental
      student's 1) state of residency and 2) gender to his or her practice location in
      a rural Nebraska community after graduation. Previous research has demonstrated
      that dental students generally locate their practices near their place of rearing
      and that male graduates are more likely than female graduates to locate in rural
      areas. Dental student data for all University of Nebraska Medical Center College
      of Dentistry graduates from 1989 to 2008 (n=879) were analyzed. Descriptive and
      quantitative analyses were performed utilizing SPSS software (version 17.0). Chi
      square and odds ratio analyses were also conducted. In contrast to previous
      research, women dentists who remained in the state after graduation were more
      likely to locate their practice in a rural community than were male dentists: 59
      percent and 48.5 percent, respectively. Nonresidents who remained in the state
      after graduation were also more likely to locate in a rural community than were
      residents: 69 percent and 51 percent, respectively. Dental schools may find this
      information useful as state officials and policymakers look to dental schools for
      leadership in addressing dental workforce needs, especially in rural/underserved
      areas.

PMID- 20679453
TI  - A longitudinal study of stress in first-year dental students.
AB  - This study examines the association of stress with performance and health in
      first-year dental students and changes in the amount and sources of stress over
      one year. Students at four U.S. dental schools completed the Dental Environment
      Stress (DES) scale, Perceived Stress Scale (PSS), stress rating, and demographic
      questions at the start of their first year of school (baseline), 11.7 weeks, and
      one year later when first-year GPA, illnesses, health ratings, and symptom
      frequency were also assessed. Overall, 296 (186 men, 110 women) responded at
      baseline and after one year; 205 responded all three times. Stress scores were
      negatively correlated with GPA (DES, p=.006; PSS, p=.04; stress rating, p=.002)
      and with physical and emotional health ratings (p's< or =.002), but positively
      associated with illness (p<.05), symptoms (p<.0001), and symptom frequency
      (p's<.05). Stress was higher after one year (p's<.001) and varied by school
      (p<.0001). Women (p<.01), younger (p<.003), and single students (p<.03) had
      higher stress at baseline, but after one year, there were no differences by
      gender, age, or marital status. Ratings for items on the Dental Environment
      Stress scale related to schoolwork were high at baseline and increased further by
      one year (p's< or =.0001); items related to school atmosphere had low ratings
      initially with large increases over time (p's<.0001). In conclusion, stress
      increases over time in first-year dental students and is related to detrimental
      effects on performance and health. Variation between schools may reflect
      different teaching methods. Changes in sources of stress may reflect the
      different contributions of anticipatory and situational stress over time. First
      year dental students may benefit from stress reduction programs.

PMID- 20679454
TI  - Assessing the content, presentation, and readability of dental informed consents.
AB  - Informed consents are important aids in helping patients make optimal decisions.
      Little knowledge exists about the quality of dental informed consents. Fifty-two
      informed consents used throughout the University of Texas Health Science Center
      at Houston Dental Branch were evaluated based on the quality of their content,
      readability, and presentation. Content quality was judged on four basic elements:
      description of procedure, risk, benefits, and alternatives. Of the clinical
      consents, 26 percent of forms contained all four of the basic content elements,
      48 percent contained three of four elements, 16 percent contained two of four
      elements, and 10 percent contained one of four elements. Presentation quality was
      judged on twelve criteria items. The average clinical consent included seven out
      of twelve presentation items, and the average nonclinical consent included eight
      out of twelve items. Readability was judged using three standard instruments for
      rating readability: Flesch Reading Ease, Flesch-Kincaid Grade-Level, and Simple
      Measure of Gobbledygook (SMOG) grading. Average Flesch-Kincaid Grade-Level was
      12.7 (range, 7.4 to 19.1), significantly higher than the recommended ninth grade
      level (p<.001). The results suggest that many existing dental informed consents
      may be improved by 1) increasing the comprehensiveness of the content, 2)
      improving the design and layout, and 3) reducing the readability levels for
      patient comprehension.

PMID- 20679455
TI  - Influence of the ICDAS e-learning program for occlusal caries detection on dental
      students.
AB  - The aim of this study was to evaluate the influence of ICDAS training in a group
      of dental students for occlusal caries detection in permanent teeth. Premolars
      and molars (N=104) with occlusal surfaces varying from ICDAS scores 0 to 6 were
      cleaned, one occlusal site per tooth was selected, and a photograph taken to
      identify the site. Eight senior dental students examined the teeth twice with a
      one-week interval between examinations during each of two phases: before and
      after the ICDAS e-learning program. Teeth were histologically assessed for caries
      extension. Intraclass correlation coefficients for intra- and interexaminer
      repeatability were high, both before (0.75 and 0.72, respectively) and after e
      learning (0.82 and 0.78, respectively). The ICDAS scores decreased significantly
      from before to after e-learning (p=0.0001). Correlation between ICDAS scores and
      histology scores was moderate (0.57 before e-learning and 0.61 after). Although
      the ROC curve shows an improvement in the use of the ICDAS scoring after e
      learning, the difference was not significant (p=0.10). Specificity of the ICDAS
      scores significantly improved after e-learning (77 percent vs. 36 percent), and
      sensitivity was reduced slightly after e-learning (87 percent vs. 92 percent).
      The ICDAS e-learning program improved the performance of the diagnostic skills of
      the investigated students for the detection of occlusal caries lesions.

PMID- 20679456
TI  - Assessment of surgical competence in North American graduate periodontics
      programs: a survey of current practices.
AB  - This cross-sectional study was designed to document the methods utilized by North
      American graduate periodontics programs in assessing their residents' surgical
      skills. A survey of clinical skills assessment was mailed to directors of all
      fifty-eight graduate periodontics programs in Canada and the United States.
      Thirty-four programs (59 percent) responded. The data collected were analyzed
      using SPSS version 15.0. The results demonstrate that the most common practice
      for providing feedback and documenting residents' surgical skills in the programs
      surveyed was daily one-on-one verbal feedback given by an instructor. The next
      two most commonly reported methods were a standard checklist developed at program
      level and a combination of a checklist and verbal comments. The majority of the
      programs reported that the instructors met collectively once per term to evaluate
      the residents' progress. The results suggest that graduate periodontics programs
      provide their residents frequent opportunities for daily practice with verbal
      feedback from instructors. However, assessment strategies identified in other
      health professions as beneficial in fostering the integration of clinical skills
      practices are not employed.

PMID- 20679457
TI  - Effect of a training model in local anesthesia teaching.
AB  - The aim of this study was to evaluate the preclinical use of a training model in
      local anesthesia teaching on the subsequent clinical administration of a local
      anesthetic. Sixty-five dental students gave their first injection to a fellow
      dental student: twenty-two students after previous experience on a training model
      and forty-three without this training. After the injection, the opinions of both
      the student who performed the injection and the recipient were explored by
      questionnaires. Use of a training model did not affect the self-reported opinion
      of the students who performed the injection. However, the recipients of the
      injection considered students who exercised on the training model significantly
      more confident and calm, and reported a near-significant decrease in level of
      pain during insertion of the needle and feeling of a tingling lip. These results
      suggest that use of preclinical training models in local anesthesia teaching may
      have beneficial effects.

PMID- 20679458
TI  - Development of a visio-haptic integrated dental training simulation system.
AB  - The use of haptic devices in the medical field has become widespread in the last
      decade. In this study, a visio-haptic dental training system is developed using
      haptic and stereoscopic devices. Several advantages are offered by such a
      simulation system, including effective learning without any fear of making
      mistakes on a patient, possibility of repeating various dental operations, ease
      of evaluating student performance, and low-cost dental training even without an
      instructor. In this study, the biomechanical properties of enamel, dentin, pulp,
      and caries were modeled, and the parameters were fine-tuned to provide more
      realistic haptic sensations. Maxillary and mandibular dental arches and various
      dental instruments such as mouth mirror, probe, and dental drills were modeled in
      a 3D virtual environment. Probing and cavity preparation on teeth were
      implemented in the training system. Various graphical rendering methods (Surface
      Rendering in CPU, Iso-Surface Rendering, and Ray-Casting in GPU) were implemented
      and compared in performance. The implementation details and the software
      structure used are described. Finally, detailed performance tests by a group of
      dentists are conducted, and the results of these tests are presented. The
      performance tests found that dentists have a strong motivation to use the system
      and that in the aspects of usability, clarity, effectiveness, help/support
      provided, and satisfaction, the users' responses were above average.

PMID- 20679459
TI  - Using evaluation to enhance educational support for dental teams in the UK.
AB  - Each United Kingdom regional postgraduate deanery offers courses and educational
      support for the NHS (National Health Service) primary care dental team, primarily
      through networks of tutors (dental educators). After reporting literature on
      effective continuing education and the role of evaluation, this article provides
      an analysis of five educational evaluations (2005-08), identifying key messages
      and distilling ways to enhance educational support for the UK dental team. These
      evaluations adopted case study design and principally employed interviews (n=51)
      and questionnaires (n=221). The studies' key messages and recommendations are as
      follows: clarify dental educator roles; provide strategic management and
      educational support for educators; ensure continuing education is matched to the
      learning needs of dental teams and specific groups; and use practice (office)
      visits to support practice (team) development plans. Evaluation enables
      initiatives to be evidence-informed, focus effort where most needed, argue for
      continued funding, and give voice to stakeholders. However, there is added value
      in a collective consideration of evaluation findings from related studies. Doing
      this has identified ways to enhance the strategic development of educational
      support for the UK dental team and is applicable in a wider context both
      nationally and internationally.

PMID- 20679462
TI  - 99Mo/99mTc generator shortage: free, Web-based software.

PMID- 20679463
TI  - Langstrom receives de Hevesy Award.

PMID- 20679464
TI  - Mathis receives Aebersold Award.

PMID- 20679467
TI  - A new vision for the MICoE.

PMID- 20679470
TI  - The XbaI G>T polymorphism of the glucose transporter 1 gene modulates 18F-FDG
      uptake and tumor aggressiveness in breast cancer.
AB  - We investigated the relevance of single-nucleotide polymorphisms (SNPs) in the
      glucose transporter 1 (GLUT1) gene to the uptake of (18)F-FDG and tumor
      aggressiveness in breast cancer. METHODS: In 52 individuals with breast cancer, a
      diagnostic PET/CT scan was obtained, and the standardized uptake value was
      determined as a measure of (18)F-FDG uptake using a region-of-interest technique.
      Three GLUT1 SNPs (XbaI G>T, HpyCH4V A>T, and HaeIII T>C) were investigated in
      genomic DNA that was isolated from the paraffin-embedded specimens of all
      patients. Tumors were typed and graded according to the World Health Organization
      classifications. RESULTS: The GG genotype of the XbaI G>T SNP was associated with
      increased tumor uptake of (18)F-FDG, with a mean standardized uptake value of
      11.7 (TT/GT genotypes, 5.9; P = 0.03). Furthermore, the GG genotype was
      positively related to enhanced tumor proliferation (mitotic count, P = 0.01). In
      line with this finding, the GG genotype was absent in grade 1 carcinomas and
      increasingly prevalent in tumors with higher malignancy (grade 2, 28.0%; grade 3,
      50%; P = 0.04). CONCLUSION: This study found that the XbaI G>T SNP of the GLUT1
      gene is associated with an increased (18)F-FDG uptake and a more advanced tumor
      grade or growth in breast cancer. Thus, this genetic variant might favor
      aggressive phenotypes by modulating the efficiency of cancer cells to recruit
      glucose and escalate growth rate, suggesting the XbaI G>T SNP as a proliferation
      related prognostic factor.

PMID- 20679471
TI  - Impaired cardiac sympathetic innervation and myocardial perfusion are related to
      lethal arrhythmia: quantification of cardiac tracers in patients with ICDs.
AB  - Despite widespread prophylactic use of implantable cardioverter defibrillator
      (ICD) therapy, sudden cardiac death and refractory arrhythmia events are still
      important clinical issues to be overcome. We examined whether the impairment of
      cardiac sympathetic innervation and myocardial perfusion is responsible for
      lethal arrhythmic events and has prognostic value by comparing conventional
      clinical indices. METHODS: In consecutive ICDs implanted in 60 patients, cardiac
      uptake of (123)I-metaiodobenzylguanidine and (99m)Tc-tetrofosmin at rest was
      quantified, and then patients were prospectively followed with endpoints of
      appropriate ICD shocks or cardiac death. Cardiac metaiodobenzylguanidine activity
      was quantified as a heart-to-mediastinum ratio (HMR), and impaired tetrofosmin
      uptake was graded as a summed score (SS) using a computerized technique with a
      percentage of tracer uptake. RESULTS: During a mean 29-mo interval, ICD shock was
      documented in 30 patients (50%); 3 cardiac deaths were also observed in this
      group of patients. Patients with ICD shocks had a significantly smaller HMR and a
      greater SS than did those without (1.73 +/- 0.34 vs. 2.06 +/- 0.46, P = 0.003,
      and 18.0 +/- 16.2 vs. 5.7 +/- 4.4, P = 0.001, respectively). Kaplan-Meier
      analysis showed that patients who had both an HMR of 1.90 or less and an SS of 12
      or greater had a significantly greater ICD discharge rate than did those who had
      both an HMR greater than 1.90 and an SS less than 12 (94% vs. 18%, P < 0.005)
      (log rank, 15.14; P < 0.0005). Multivariate analysis with a Cox model identified
      the greatest Wald chi(2) of 6.454 and a hazard ratio of 3.857 (P = 0.011) when an
      HMR of 1.9 or less and tetrofosmin SS of 12 or greater were combined. CONCLUSION:
      Impairment of cardiac sympathetic innervation and myocardial perfusion is related
      to lethal arrhythmic events leading to sudden death, and the combined assessment
      of these can identify patients for whom prophylactic ICD use has the greatest
      potential.

PMID- 20679472
TI  - Molecular imaging of cardiac sympathetic innervation by 11C-mHED and PET: from
      man to mouse?
AB  - Dysfunction of the sympathetic nervous system underlies many cardiac diseases and
      can be assessed by molecular imaging using PET in humans. Small-animal PET should
      enable noninvasive quantitation of the sympathetic nervous system in mouse models
      of human disease. For mice, however, the radioactivity needed to give acceptable
      image quality may be associated with a mass of unlabeled compound sufficient to
      block the binding of radioligand to its target. The present study assesses the
      feasibility of using [N-methyl-(11)C]meta-hydroxyephedrine ((11)C-mHED) to
      measure norepinephrine reuptake in humans, to determine cardiac innervation in
      mice. METHODS: Anesthetized mice were placed in a small-animal PET scanner. (11)C
      mHED (containing 18% precursor metaraminol) was injected via a tail vein into
      each animal simultaneously. Fifteen minutes later, animals were injected with
      saline or metaraminol which competes with mHED for norepinephrine reuptake. (18)F
      FDG was injected at 60 min to identify heart regions. After reconstruction of the
      list-mode data, radioactivity in myocardial regions was computed using in-house
      software, and time-activity curves were plotted. RESULTS: Hearts were clearly
      visualized after injection of (11)C-mHED. Injection of metaraminol at doses less
      than 50 nmol x kg(-1) had no effect, whereas doses greater than 100 nmol x kg(-1)
      caused a dose-dependent loss of specifically bound radioactivity. CONCLUSION:
      (11)C-mHED was successfully used to visualize and assess myocardial innervation
      in mice. Uptake of (11)C-mHED is displaceable by the false transmitter
      metaraminol. The total molar dose of metaraminol and (11)C-mHED must be
      considered in the analysis of PET data.

PMID- 20679473
TI  - Validation of a radiographic scoring system for haemochromatosis arthropathy.
AB  - BACKGROUND: Arthropathy is one of the earliest and most common manifestations of
      hereditary haemochromatosis with a significant impact on quality of life.
      Although its radiographic features are well known, there is no assessment tool
      for their evaluation. OBJECTIVE: To develop and validate a novel scoring system
      for the evaluation of radiographic features of haemochromatosis arthropathy.
      METHODS: A dichotomous scoring system assessing four radiographic features of
      haemochromatosis arthropathy and a 4-grade scale reflecting severity of
      radiographic change have been developed. Standard radiographs (hand, wrist, knee
      and ankle) of 170 subjects (116 male, 54 female) with genetically confirmed
      haemochromatosis and laboratory signs of iron overload were assessed by three
      readers and construct validity, feasibility and cross-sectional reliability
      (intrareader and inter-reader) were assessed. RESULTS: Intrareader and inter
      reader reliability as assessed by percentage pairwise agreement and Cohen's
      weighed kappa were good to excellent for most features and locations evaluated.
      Radiographic scores correlated well with clinical parameters (bony swollen joint
      count, hand function and physician's global health assessment; Pearson's
      correlation, r2=0.18-0.62, p<0.0001). A complete set of radiographs took 3.4 +/-
      1.2 (mean +/- SD) min to be assessed. An atlas of characteristic radiographic
      features was compiled. CONCLUSION: A feasible and reliable radiological
      assessment tool for the evaluation of haemochromatosis arthropathy has been
      validated and an atlas of characteristic radiographic features provided.

PMID- 20679474
TI  - Skin thickness progression rate: a predictor of mortality and early internal
      organ involvement in diffuse scleroderma.
AB  - OBJECTIVE: To examine the association of skin thickness progression rate (STPR)
      with mortality, and as a predictor of future internal organ involvement in an
      inception cohort of diffuse cutaneous systemic sclerosis (SSc) patients. METHODS:
      Diffuse cutaneous SSc patients older than 16 years of age evaluated at the
      University of Pittsburgh within 2 years of the first evidence of skin thickening
      between 1980 and 2005 were eligible. The authors calculated the STPR on these
      patients, and examined the relationship of this variable to the development of
      early internal organ involvement and short-term mortality using logistic
      regression. RESULTS: 826 patients were included in the analysis. Patients with a
      rapid STPR experienced significantly reduced short-term survival at 1 and 2 years
      from the time of first Pittsburgh evaluation (p=0.002). Patients with a rapid
      STPR were more likely to develop renal crisis within 1-2 years of follow-up.
      Rapid STPR was found to be an independent predictor of both mortality (OR 1.72;
      95% CI 1.13 to 2.62; p=0.01) and 'renal crisis' (OR 2.05, 95% CI 1.10 to 3.85;
      p=0.02) within 2 years from first evaluation. CONCLUSION: The STPR is an easy
      measure to perform at the time of initial evaluation for identifying those
      diffuse cutaneous SSc patients who are at increased risk of mortality and the
      development of renal crisis during the following 2 years.

PMID- 20679475
TI  - Decrease in immunoglobulin free light chains in patients with rheumatoid
      arthritis upon rituximab (anti-CD20) treatment correlates with decrease in
      disease activity.
AB  - OBJECTIVES: Immunoglobulin (Ig) free light chains (FLCs) are short-lived B cell
      products that contribute to inflammation in several experimental disease models.
      In this study, FLC concentrations in inflamed joints of patients with rheumatoid
      arthritis (RA) as compared to patients with osteoarthritis were investigated. In
      addition, the relationship of FLCs and disease activity upon B cell depletion
      (rituximab) in patients with RA was studied. METHODS: Synovial fluid (SF) and
      tissue from patients with RA were analysed for local presence of FLCs using ELISA
      and immunohistochemistry. In addition, FLC concentrations were measured (at
      baseline, 3 and 6 months after treatment) in 50 patients with RA with active
      disease who were treated with rituximab. Changes in FLCs were correlated to
      changes in disease activity and compared to alterations in IgM, IgG, IgA, IgM
      rheumatoid factor (RF) and IgG-anti-citrullinated protein antibody (ACPA)
      concentrations. RESULTS: FLCs were detected in synovial tissue from patients with
      RA, and high FLC concentrations were found in SF from inflamed joints, which
      positively correlate with serum FLC concentrations. Serum FLC concentrations
      significantly correlated with disease activity score using 28 joint counts,
      erythrocyte sedimentation rate (ESR) and C reactive protein, and changes in FLC
      correlated with clinical improvement after rituximab treatment. Moreover, effect
      of treatment on FLC concentrations discriminated clinical responders from non
      responders, whereas IgM-RF and IgG-ACPA significantly decreased in both patient
      groups. CONCLUSIONS: FLCs are abundantly present in inflamed joints and FLC
      levels correlate with disease activity. The correlation of FLC concentrations and
      disease activity indicates that FLCs may be relevant biomarkers for treatment
      response to rituximab in patients with RA and suggests that targeting FLC may be
      of importance in the therapy of RA.

PMID- 20679476
TI  - Interleukin 18 induces angiogenesis in vitro and in vivo via Src and Jnk kinases.
AB  - BACKGROUND: Interleukin 18 (IL-18) is a novel mediator of angiogenesis in
      rheumatoid arthritis (RA). OBJECTIVE: To examine the role of IL-18 in RA
      angiogenesis and the signalling mechanisms involved. METHODS: Human dermal
      microvascular endothelial cell (HMVEC) chemotaxis, capillary morphogenesis assays
      and Matrigel plug angiogenesis assays were performed in vivo using IL-18 with or
      without signalling inhibitors. A novel model of angiogenesis was devised using
      dye-tagged HMVECs to study their homing into RA and normal (NL) synovial tissues
      (STs) engrafted in severe combined immunodeficient (SCID) mice. RESULTS: IL-18
      mediated angiogenesis depended on Src and Jnk, as the inhibitors of Src and Jnk
      blocked IL-18-induced HMVEC chemotaxis, tube formation and angiogenesis in
      Matrigel plugs. However, inhibitors of Janus kinase 2, p38, MEK,
      phosphatidylinositol-3-kinase and neutralising antibodies to vascular endothelial
      growth factor or stromal derived factor-1alpha did not alter IL-18-induced HMVEC
      migration. These results were confirmed with Jnk or Src sense or antisense
      oligodeoxynucleotides. Moreover, IL-18 induced phosphorylation of Src and Jnk in
      HMVECs. As proof of principle, IL-18 null mice had a significantly decreased
      angiogenesis compared with wild-type mice in Matrigel plug angiogenesis assays in
      vivo. IL-18 markedly enhanced mature HMVEC homing to human RA ST compared with NL
      ST in SCID mice, confirming the role of IL-18-induced angiogenesis in RA ST in
      vivo. CONCLUSION: Targeting IL-18 or its signalling intermediates may prove to be
      a potentially novel therapeutic strategy for angiogenesis-dependent diseases,
      such as RA.

PMID- 20679477
TI  - Cellular prion protein promotes regeneration of adult muscle tissue.
AB  - It is now well established that the conversion of the cellular prion protein,
      PrP(C), into its anomalous conformer, PrP(Sc), is central to the onset of prion
      disease. However, both the mechanism of prion-related neurodegeneration and the
      physiologic role of PrP(C) are still unknown. The use of animal and cell models
      has suggested a number of putative functions for the protein, including cell
      signaling, adhesion, proliferation, and differentiation. Given that skeletal
      muscles express significant amounts of PrP(C) and have been related to PrP(C)
      pathophysiology, in the present study, we used skeletal muscles to analyze
      whether the protein plays a role in adult morphogenesis. We employed an in vivo
      paradigm that allowed us to compare the regeneration of acutely damaged hind-limb
      tibialis anterior muscles of mice expressing, or not expressing, PrP(C). Using
      morphometric and biochemical parameters, we provide compelling evidence that the
      absence of PrP(C) significantly slows the regeneration process compared to wild
      type muscles by attenuating the stress-activated p38 pathway, and the consequent
      exit from the cell cycle, of myogenic precursor cells. Demonstrating the
      specificity of this finding, restoring PrP(C) expression completely rescued the
      muscle phenotype evidenced in the absence of PrP(C).

PMID- 20679478
TI  - The RNA recognition motif of eukaryotic translation initiation factor 3g (eIF3g)
      is required for resumption of scanning of posttermination ribosomes for
      reinitiation on GCN4 and together with eIF3i stimulates linear scanning.
AB  - Recent reports have begun unraveling the details of various roles of individual
      eukaryotic translation initiation factor 3 (eIF3) subunits in translation
      initiation. Here we describe functional characterization of two essential
      Saccharomyces cerevisiae eIF3 subunits, g/Tif35 and i/Tif34, previously suggested
      to be dispensable for formation of the 48S preinitiation complexes (PICs) in
      vitro. A triple-Ala substitution of conserved residues in the RRM of g/Tif35
      (g/tif35-KLF) or a single-point mutation in the WD40 repeat 6 of i/Tif34 (i/tif34
      Q258R) produces severe growth defects and decreases the rate of translation
      initiation in vivo without affecting the integrity of eIF3 and formation of the
      43S PICs in vivo. Both mutations also diminish induction of GCN4 expression,
      which occurs upon starvation via reinitiation. Whereas g/tif35-KLF impedes
      resumption of scanning for downstream reinitiation by 40S ribosomes terminating
      at upstream open reading frame 1 (uORF1) in the GCN4 mRNA leader, i/tif34-Q258R
      prevents full GCN4 derepression by impairing the rate of scanning of
      posttermination 40S ribosomes moving downstream from uORF1. In addition, g/tif35
      KLF reduces processivity of scanning through stable secondary structures, and
      g/Tif35 specifically interacts with Rps3 and Rps20 located near the ribosomal
      mRNA entry channel. Together these results implicate g/Tif35 and i/Tif34 in
      stimulation of linear scanning and, specifically in the case of g/Tif35, also in
      proper regulation of the GCN4 reinitiation mechanism.

PMID- 20679479
TI  - mDia1 targets v-Src to the cell periphery and facilitates cell transformation,
      tumorigenesis, and invasion.
AB  - The small GTPase Rho regulates cell morphogenesis through remodeling of the actin
      cytoskeleton. While Rho is overexpressed in many clinical cancers, the role of
      Rho signaling in oncogenesis remains unknown. mDia1 is a Rho effector producing
      straight actin filaments. Here we transduced mouse embryonic fibroblasts from
      mDia1-deficient mice with temperature-sensitive v-Src and examined the
      involvement and mechanism of the Rho-mDia1 pathway in Src-induced oncogenesis. We
      showed that in v-Src-transduced mDia1-deficient cells, formation of actin
      filaments is suppressed, and v-Src in the perinuclear region does not move to
      focal adhesions upon a temperature shift. Consequently, membrane translocation of
      v-Src, v-Src-induced morphological transformation, and podosome formation are all
      suppressed in mDia1-deficient cells with impaired tyrosine phosphorylation. mDia1
      deficient cells show reduced transformation in vitro as examined by focus
      formation and colony formation in soft agar and exhibit suppressed tumorigenesis
      and invasion when implanted in nude mice in vivo. Given overexpression of c-Src
      in various cancers, these findings suggest that Rho-mDia1 signaling facilitates
      malignant transformation and invasion by manipulating the actin cytoskeleton and
      targeting Src to the cell periphery.

PMID- 20679480
TI  - Impaired binding of 14-3-3 to C-RAF in Noonan syndrome suggests new approaches in
      diseases with increased Ras signaling.
AB  - The Ras-RAF-mitogen-activated protein kinase (Ras-RAF-MAPK) pathway is overactive
      in many cancers and in some developmental disorders. In one of those disorders,
      namely, Noonan syndrome, nine activating C-RAF mutations cluster around Ser(259),
      a regulatory site for inhibition by 14-3-3 proteins. We show that these mutations
      impair binding of 14-3-3 proteins to C-RAF and alter its subcellular localization
      by promoting Ras-mediated plasma membrane recruitment of C-RAF. By presenting
      biophysical binding data, the 14-3-3/C-RAFpS(259) crystal structure, and cellular
      analyses, we indicate a mechanistic link between a well-described human
      developmental disorder and the impairment of a 14-3-3/target protein interaction.
      As a broader implication of these findings, modulating the C-RAFSer(259)/14-3-3
      protein-protein interaction with a stabilizing small molecule may yield a novel
      potential approach for treatment of diseases resulting from an overactive Ras-RAF
      MAPK pathway.

PMID- 20679481
TI  - MeCP2 binds cooperatively to its substrate and competes with histone H1 for
      chromatin binding sites.
AB  - Sporadic mutations in the hMeCP2 gene, coding for a protein that preferentially
      binds symmetrically methylated CpGs, result in the severe neurological disorder
      Rett syndrome (RTT). In the present work, employing a wide range of experimental
      approaches, we shed new light on the many levels of MeCP2 interaction with DNA
      and chromatin. We show that strong methylation-independent as well as methylation
      dependent binding by MeCP2 is influenced by DNA length. Although MeCP2 is
      strictly monomeric in solution, its binding to DNA is cooperative, with dimeric
      binding strongly correlated with methylation density, and strengthened by nearby
      A/T repeats. Dimeric binding is abolished in the F155S and R294X severe RTT
      mutants. MeCP2 also binds chromatin in vitro, resulting in compaction-related
      changes in nucleosome architecture that resemble the classical zigzag motif
      induced by histone H1 and considered important for 30-nm-fiber formation. In vivo
      chromatin binding kinetics and in vitro steady-state nucleosome binding of both
      MeCP2 and H1 provide strong evidence for competition between MeCP2 and H1 for
      common binding sites. This suggests that chromatin binding by MeCP2 and H1 in
      vivo should be viewed in the context of competitive multifactorial regulation.

PMID- 20679482
TI  - The type I interferon signaling pathway is a target for glucocorticoid
      inhibition.
AB  - Type I interferon (IFN) is essential for host defenses against viruses; however,
      dysregulated IFN signaling is causally linked to autoimmunity, particularly
      systemic lupus erythematosus. Autoimmune disease treatments rely on
      glucocorticoids (GCs), which act via the GC receptor (GR) to repress
      proinflammatory cytokine gene transcription. Conversely, cytokine signaling
      through cognate Jak/STAT pathways is reportedly unaffected or even stimulated by
      GR. Unexpectedly, we found that GR dramatically inhibited IFN-stimulated gene
      (ISG) expression in macrophages. The target of inhibition, the heterotrimeric
      STAT1-STAT2-IRF9 (ISGF3) transcription complex, utilized the GR cofactor
      GRIP1/TIF2 as a coactivator. Consequently, GRIP1 knockdown, genetic ablation, or
      depletion by GC-activated GR attenuated ISGF3 promoter occupancy, preinitiation
      complex assembly, and ISG expression. Furthermore, this regulatory loop was
      restricted to cell types such as macrophages expressing the GRIP1 protein at
      extremely low levels, and pharmacological disruption of the GR-GRIP1 interaction
      or transient introduction of GRIP1 restored RNA polymerase recruitment to target
      ISGs and the subsequent IFN response. Thus, type I IFN is a cytokine uniquely
      controlled by GR at the levels of not only production but also signaling through
      antagonism with the ISGF3 effector function, revealing a novel facet of the
      immunosuppressive properties of GCs.

PMID- 20679483
TI  - Requirement of JIP1-mediated c-Jun N-terminal kinase activation for obesity
      induced insulin resistance.
AB  - The c-Jun NH(2)-terminal kinase (JNK) interacting protein 1 (JIP1) has been
      proposed to act as a scaffold protein that mediates JNK activation. However,
      recent studies have implicated JIP1 in multiple biochemical processes.
      Physiological roles of JIP1 that are related to the JNK scaffold function of JIP1
      are therefore unclear. To test the role of JIP1 in JNK activation, we created
      mice with a germ line point mutation in the Jip1 gene (Thr(103) replaced with
      Ala) that selectively blocks JIP1-mediated JNK activation. These mutant mice
      exhibit a severe defect in JNK activation caused by feeding of a high-fat diet.
      The loss of JIP1-mediated JNK activation protected the mutant mice against
      obesity-induced insulin resistance. We conclude that JIP1-mediated JNK activation
      plays a critical role in metabolic stress regulation of the JNK signaling
      pathway.

PMID- 20679484
TI  - Drosophila MCRS2 associates with RNA polymerase II complexes to regulate
      transcription.
AB  - Drosophila MCRS2 (dMCRS2; MCRS2/MSP58 and its splice variant MCRS1/p78 in humans)
      belongs to a family of forkhead-associated (FHA) domain proteins. Whereas human
      MCRS2 proteins have been associated with a variety of cellular processes,
      including RNA polymerase I transcription and cell cycle progression, dMCRS2 has
      been largely uncharacterized. Recent data show that MCRS2 is purified as part of
      a complex containing the histone acetyltransferase MOF (males absent on first) in
      both humans and flies. MOF mediates H4K16 acetylation and regulates the
      expression of a large number of genes, suggesting that MCRS2 could also have a
      function in transcription regulation. Here, we show that dMCRS2 copurifies with
      RNA polymerase II (RNAP II) complexes and localizes to the 5' ends of genes.
      Moreover, dMCRS2 is required for optimal recruitment of RNAP II to the promoter
      regions of cyclin genes. In agreement with this, dMCRS2 is required for normal
      levels of cyclin gene expression. We propose a model whereby dMCRS2 promotes gene
      transcription by facilitating the recruitment of RNAP II preinitiation complexes
      (PICs) to the promoter regions of target genes.

PMID- 20679485
TI  - BRCT domain interactions with phospho-histone H2A target Crb2 to chromatin at
      double-strand breaks and maintain the DNA damage checkpoint.
AB  - Relocalization of checkpoint proteins to chromatin flanking DNA double-strand
      breaks (DSBs) is critical for cellular responses to DNA damage.
      Schizosaccharomyces pombe Crb2, which mediates Chk1 activation by Rad3(ATR),
      forms ionizing radiation-induced nuclear foci (IRIF). Crb2 C-terminal BRCT
      domains (BRCT(2)) bind histone H2A phosphorylated at a C-terminal SQ motif by
      Tel1(ATM) and Rad3(ATR), although the functional significance of this interaction
      is controversial. Here, we show that polar interactions of Crb2 serine-548 and
      lysine-619 with the phosphate group of phospho-H2A (gamma-H2A) are critical for
      Crb2 IRIF formation and checkpoint function. Mutations of these BRCT(2) domain
      residues have additive effects when combined in a single allele. Combining either
      mutation with an allele that eliminates the threonine-215 cyclin-dependent kinase
      phosphorylation site completely abrogates Crb2 IRIF and function. We propose that
      cooperative phosphate interactions in the BRCT(2) gamma-H2A-binding pocket of
      Crb2, coupled with tudor domain interactions with lysine-20 dimethylation of
      histone H4, facilitate stable recruitment of Crb2 to chromatin surrounding DSBs,
      which in turn mediates efficient phosphorylation of Chk1 that is required for a
      sustained checkpoint response. This mechanism of cooperative interactions with
      the gamma-H2A/X phosphate is likely conserved in S. pombe Brc1 and human Mdc1
      genome maintenance proteins.

PMID- 20679486
TI  - Loss of Hsp110 leads to age-dependent tau hyperphosphorylation and early
      accumulation of insoluble amyloid beta.
AB  - Accumulation of tau into neurofibrillary tangles is a pathological consequence of
      Alzheimer's disease and other tauopathies. Failures of the quality control
      mechanisms by the heat shock proteins (Hsps) positively correlate with the
      appearance of such neurodegenerative diseases. However, in vivo genetic evidence
      for the roles of Hsps in neurodegeneration remains elusive. Hsp110 is a
      nucleotide exchange factor for Hsp70, and direct substrate binding to Hsp110 may
      facilitate substrate folding. Hsp70 complexes have been implicated in tau
      phosphorylation state and amyloid precursor protein (APP) processing. To provide
      evidence for a role for Hsp110 in central nervous system homeostasis, we have
      generated hsp110(-)(/)(-) mice. Our results show that hsp110(-)(/)(-) mice
      exhibit accumulation of hyperphosphorylated-tau (p-tau) and neurodegeneration. We
      also demonstrate that Hsp110 is in complexes with tau, other molecular
      chaperones, and protein phosphatase 2A (PP2A). Surprisingly, high levels of PP2A
      remain bound to tau but with significantly reduced activity in brain extracts
      from aged hsp110(-)(/)(-) mice compared to brain extracts from wild-type mice.
      Mice deficient in the Hsp110 partner (Hsp70) also exhibit a phenotype comparable
      to that of hsp110(-)(/)(-) mice, confirming a critical role for Hsp110-Hsp70 in
      maintaining tau in its unphosphorylated form during aging. In addition, crossing
      hsp110(-)(/)(-) mice with mice overexpressing mutant APP (APPbetasw) leads to
      selective appearance of insoluble amyloid beta42 (Abeta42), suggesting an
      essential role for Hsp110 in APP processing and Abeta generation. Thus, our
      findings provide in vivo evidence that Hsp110 plays a critical function in tau
      phosphorylation state through maintenance of efficient PP2A activity, confirming
      its role in pathogenesis of Alzheimer's disease and other tauopathies.

PMID- 20679487
TI  - VRK2 inhibits mitogen-activated protein kinase signaling and inversely correlates
      with ErbB2 in human breast cancer.
AB  - The epidermal growth factor (EGF)-ErbB-mitogen-activated protein kinase (MAPK)
      transcription signaling pathway is altered in many types of carcinomas, and this
      pathway can be regulated by new protein-protein interactions. Vaccinia-related
      kinase (VRK) proteins are Ser-Thr kinases that regulate several signal
      transduction pathways. In this work, we study the effect of VRK2 on MAPK
      signaling using breast cancer as a model. High levels of VRK2 inhibit EGF and
      ErbB2 activation of transcription by the serum response element (SRE). This
      effect is also detected in response to H-Ras(G12V) or B-Raf(V600E) oncogenes and
      is accompanied by a reduction in phosphorylated extracellular signal-regulated
      kinase (ERK) levels, p90RSK levels, and SRE-dependent transcription. Furthermore,
      VRK2 knockdown has the opposite effect, increasing the transcriptional response
      to stimulation with EGF and leading to increased levels of ERK phosphorylation.
      The molecular mechanism lies between MAPK/ERK kinase (MEK) and ERK, since MEK
      remains phosphorylated while ERK phosphorylation is blocked by VRK2A. This
      inhibition of the ERK signaling pathway is a consequence of a direct protein
      protein interaction between VRK2A, MEK, and kinase suppressor of Ras 1 (KSR1).
      Identification of new correlations in human cancer can lead to a better
      understanding of the biology of individual tumors. ErbB2 and VRK2 protein levels
      were inversely correlated in 136 cases of human breast carcinoma. In ErbB2(+)
      tumors, there is a significant reduction in the VRK2 level, suggesting a role for
      VRK2A in ErbB2-MAPK signaling. Thus, VRK2 downregulation in carcinomas permits
      signal transmission through the MEK-ERK pathway without affecting AKT signaling,
      causing a signal imbalance among pathways that contributes to the phenotype of
      breast cancer.

PMID- 20679488
TI  - Requirement for the phospho-H2AX binding module of Crb2 in double-strand break
      targeting and checkpoint activation.
AB  - Activation of DNA damage checkpoints requires the rapid accumulation of numerous
      factors to sites of genomic lesions, and deciphering the mechanisms of this
      targeting is central to our understanding of DNA damage response. Histone
      modification has recently emerged as a critical element for the correct
      localization of damage response proteins, and one key player in this context is
      the fission yeast checkpoint mediator Crb2. Accumulation of Crb2 at ionizing
      irradiation-induced double-strand breaks (DSBs) requires two distinct histone
      marks, dimethylated H4 lysine 20 (H4K20me2) and phosphorylated H2AX (pH2AX). A
      tandem tudor motif in Crb2 directly binds H4K20me2, and this interaction is
      required for DSB targeting and checkpoint activation. Similarly, pH2AX is
      required for Crb2 localization to DSBs and checkpoint control. Crb2 can directly
      bind pH2AX through a pair of C-terminal BRCT repeats, but the functional
      significance of this binding has been unclear. Here we demonstrate that loss of
      its pH2AX-binding activity severely impairs the ability of Crb2 to accumulate at
      ionizing irradiation-induced DSBs, compromises checkpoint signaling, and disrupts
      checkpoint-mediated cell cycle arrest. These impairments are similar to that
      reported for abolition of pH2AX or mutation of the H4K20me2-binding tudor motif
      of Crb2. Intriguingly, a combined ablation of its two histone modification
      binding modules yields a strikingly additive reduction in Crb2 activity. These
      observations argue that binding of the Crb2 BRCT repeats to pH2AX is critical for
      checkpoint activity and provide new insight into the mechanisms of chromatin
      mediated genome stability.

PMID- 20679489
TI  - Renal oxygenation suppresses VHL loss-induced senescence that is caused by
      increased sensitivity to oxidative stress.
AB  - Loss of the VHL tumor suppressor is regarded as an initiating event in the
      development of clear-cell renal carcinoma. Surprisingly, loss of VHL induces
      senescence in mouse fibroblasts in vitro, a response that would restrict
      development of renal carcinoma in vivo. Typical in vitro cell culture levels of
      oxygen, however, are significantly higher than physiological levels of oxygen,
      which have been shown to abrogate senescence induced by many stimuli. Therefore,
      we investigated the oxygen dependence of VHL loss-induced senescence. Using mouse
      fibroblasts and primary renal epithelial cells in vitro, we found that VHL loss
      leads to senescence under atmospheric conditions (21% O(2)), partly through
      increasing p27 levels, but not under physiological oxygenation (2% to 5% O(2)),
      despite maintaining increased p27 expression. This suggests that VHL inactivation
      sensitizes cells to oxidative stress. In support of this concept, senescence
      following VHL loss depends on p53 activity, which decreases under the less
      stressful conditions of mild hypoxia. We confirmed these observations in vivo by
      treating kidney-specific VHL knockout animals with the potent oxidizer paraquat
      and observed a robust induction of cellular senescence. Together, these data
      demonstrate that in vivo oxygenation promotes tolerance of VHL loss in renal
      epithelia, which may promote the development of renal carcinoma.

PMID- 20679490
TI  - Distinct subregions of Swi1 manifest striking differences in prion transmission
      and SWI/SNF function.
AB  - We have recently reported that the yeast chromatin-remodeling factor Swi1 can
      exist as a prion, [SWI(+)], demonstrating a link between prionogenesis and global
      transcriptional regulation. To shed light on how the Swi1 conformational switch
      influences Swi1 function and to define the sequence and structural requirements
      for [SWI(+)] formation and propagation, we functionally dissected the Swi1
      molecule. We show here that the [SWI(+)] prion features are solely attributable
      to the first 327 amino acid residues (N), a region that is asparagine rich. N was
      aggregated in [SWI(+)] cells but diffuse in [swi(-)] cells; chromosomal deletion
      of the N-coding region resulted in [SWI(+)] loss, and recombinant N peptide was
      able to form infectious amyloid fibers in vitro, enabling [SWI(+)] de novo
      formation through a simple transformation. Although the glutamine-rich middle
      region (Q) was not sufficient to aggregate in [SWI(+)] cells or essential for
      SWI/SNF function, it significantly modified the Swi1 aggregation pattern and Swi1
      function. We also show that excessive Swi1 incurred Li(+)/Na(+) sensitivity and
      that the N/Q regions are important for this gain of sensitivity. Taken together,
      our results provide the final proof of "protein-only" transmission of [SWI(+)]
      and demonstrate that the widely distributed "dispensable" glutamine/asparagine
      rich regions/motifs might have important and divergent biological functions.

PMID- 20679491
TI  - Interferon consensus sequence binding protein (ICSBP) decreases beta-catenin
      activity in myeloid cells by repressing GAS2 transcription.
AB  - The interferon consensus sequence binding protein (ICSBP) is an interferon
      regulatory transcription factor, also referred to as IRF8. ICSBP acts as a
      suppressor of myeloid leukemia, although few target genes explaining this effect
      have been identified. In the current studies, we identified the gene encoding
      growth arrest specific 2 (GAS2) as an ICSBP target gene relevant to leukemia
      suppression. We find that ICSBP, Tel, and histone deacetylase 3 (HDAC3) bind to a
      cis element in the GAS2 promoter and repress transcription in myeloid progenitor
      cells. Gas2 inhibits calpain protease activity, and beta-catenin is a calpain
      substrate in these cells. Consistent with this, ICSBP decreases beta-catenin
      protein and activity in a Gas2- and calpain-dependent manner. Conversely,
      decreased ICSBP expression increases beta-catenin protein and activity by the
      same mechanism. This is of interest, because decreased ICSBP expression and
      increased beta-catenin activity are associated with poor prognosis and blast
      crisis in chronic myeloid leukemia (CML). We find that the expression of Bcr/abl
      (the CML oncoprotein) increases Gas2 expression in an ICSBP-dependent manner.
      This results in decreased calpain activity and a consequent increase in beta
      catenin activity in Bcr/abl-positive (Bcr/abl(+)) cells. Therefore, these studies
      have identified a Gas2/calpain-dependent mechanism by which ICSBP influences beta
      catenin activity in myeloid leukemia.

PMID- 20679492
TI  - Thioredoxin regulates multiple hydrogen peroxide-induced signaling pathways in
      Candida albicans.
AB  - The ability of the major systemic fungal pathogen of humans, Candida albicans, to
      sense and respond to reactive oxygen species (ROS), such as H(2)O(2) generated by
      the host immune system, is required for survival in the host. However, the
      intracellular signaling mechanisms underlying such responses are poorly
      understood. Here, we show that thioredoxin (Trx1), in addition to its antioxidant
      activity, plays a central role in coordinating the response of C. albicans to ROS
      by regulating multiple pathways. In particular, Trx1 function is important for
      H(2)O(2)-induced phosphorylation of the Hog1 stress-activated protein kinase and
      to reverse H(2)O(2)-induced oxidation and activation of the AP-1 like
      transcription factor Cap1. Furthermore, Trx1 regulates H(2)O(2)-induced
      hyperpolarized bud growth in a mechanism that involves activation of the Rad53
      checkpoint kinase. Consistent with its key roles in responses to ROS, cells
      lacking Trx1 displayed significantly attenuated virulence in a murine model of C.
      albicans systemic infection. Collectively, our data indicate that Trx1 has a
      multifaceted role in H(2)O(2) signaling and promotes C. albicans survival in the
      host.

PMID- 20679493
TI  - Rhythm-promoting actions of exercise in mice with deficient neuropeptide
      signaling.
AB  - Daily exercise promotes physical health as well as improvements in mental and
      neural functions. Studies in intact wild-type (WT) rodents have revealed that the
      brain's suprachiasmatic nuclei (SCN), site of the main circadian pacemaker, are
      also responsive to scheduled wheel running. It is unclear, however, if and how
      animals with a dysfunctional circadian pacemaker respond to exercise. Here, we
      tested whether scheduled voluntary exercise (SVE) in a running wheel for 6 hours
      per day could promote neural and behavioral rhythmicity in animals whose
      circadian competence is compromised through genetically targeted loss of
      vasoactive intestinal polypeptide (VIP(-/-) mice) or its VPAC(2) receptor (Vipr2(
      /-) mice). We report that in constant dark (DD), rhythmic VIP(-/-) and Vipr2(-/-)
      mice show weak free-running rhythms with a period of <23 hours and all wild-type
      mice are strongly rhythmic with approximately 23.5-hour periodicity. VIP(-/-) and
      Vipr2(-/-) mice rapidly (<7 days) synchronize to daily SVE, while WT mice take
      much longer (>35 days). Following 21 to 50 days of SVE, WT mice show small
      changes in their rhythms, and most Vipr2(-/-) mice now sustain robust near 24
      hour behavioral rhythms, whereas very few VIP(-/-) mice do. This study
      demonstrates that scheduled daily exercise can markedly improve circadian rhythms
      in behavioral activity and raises the possibility that this noninvasive approach
      may be useful as an intervention in clinical etiologies in which there are
      dysfunctions of circadian time keeping.

PMID- 20679494
TI  - Entrainment of circadian rhythm by ambient temperature cycles in mice.
AB  - Much is known about how environmental light-dark cycles synchronize circadian
      rhythms in animals. The ability of environmental cycles of ambient temperature to
      synchronize circadian rhythms has also been investigated extensively but mostly
      in ectotherms. In the present study, the synchronization of the circadian rhythm
      of running-wheel activity by environmental cycles of ambient temperature was
      studied in laboratory mice. Although all mice were successfully entrained by a
      light-dark cycle, only 60% to 80% of the mice were entrained by temperature
      cycles (24-32 degrees C or 24-12 degrees C), and attainment of stable entrainment
      seemed to take longer under temperature cycles than under a light-dark cycle.
      This suggests that ambient temperature cycles are weaker zeitgebers than light
      dark cycles, which is consistent with the results of the few previous studies
      using mammalian species. Whereas 80% of the mice were entrained by 24-h
      temperature cycles, only 60% were entrained by 23-h cycles, and none was
      entrained by 25-h cycles. The results did not clarify whether entrainment by
      temperature cycles is caused directly by temperature or indirectly through a
      temperature effect on locomotor activity, but it is clear that the rhythm of
      running-wheel activity in mice can be entrained by ambient temperature cycles in
      the nonnoxious range.

PMID- 20679495
TI  - Circadian foraging rhythms of bumblebees monitored by radio-frequency
      identification.
AB  - Circadian clocks enable organisms to anticipate changes of environmental
      conditions. In social insects, the colony as a superorganism has a foraging
      rhythm aligned to the diurnal patterns of resource availability. Within this
      colony rhythm, the diurnal patterns of individuals are embedded, and various
      tasks within the colony are performed at different times by different individuals
      to best serve the colony as a whole. Recent studies have shown that social cues
      influence the traits of the circadian clock in social insects, but keeping track
      of the activity of individual workers is not an easy task. Here the authors use
      fully automatic radio-frequency identification (RFID) to analyze the circadian
      rhythms of bumblebee foragers (Bombus terrestris) in the normal social context of
      their nest. They monitored their foraging patterns under different light
      conditions in the laboratory, including light:dark cycles (LD) as well as
      constant darkness (DD) and constant light conditions (LL). Their results show
      that the majority of bumblebee foragers exhibit robust circadian rhythms in LD
      under laboratory conditions, while they show free-running rhythms both in DD and
      LL, with free-running periods being significantly shorter in LL conditions. The
      authors also found that bumblebee workers show an increased level of arrhythmic
      activity ("death dance") in the hours or days before their death.

PMID- 20679496
TI  - Endogenous rhythms of seasonal migratory body mass changes and nocturnal
      restlessness in different populations of Northern Wheatear Oenanthe oenanthe.
AB  - The Northern Wheatear (Oenanthe oenanthe) is a migratory bird species that shows
      different strategies of migration between populations, adapted to cope with
      different ecological barriers. This raises the question whether and to which
      extent these adaptations are endogenously determined. We studied seasonal
      patterns of body mass change and nocturnal restlessness in wheatears from
      Iceland, which face an initial sea crossing of at least 800 km; from Norway,
      which fly a similar distance as Icelandic birds but without a long sea crossing;
      and from Morocco, which fly a shorter distance to reach their wintering grounds.
      To isolate the endogenous component of the regulation of these migratory traits,
      we kept the wheatears in a "common garden," all 3 populations experiencing the
      same environmental conditions and a constant photoperiod during their first year
      of life. Icelandic birds showed a greater increase of their body mass in autumn
      than the other 2 populations, indicating preparation for the initial barrier
      crossing. The autumnal timing of nocturnal restlessness and the total activity
      during autumn were related to the distance to be covered, although the
      differences between populations were smaller than expected. In all 3 populations,
      body mass increased to a greater extent in autumn than in spring, whereas
      nocturnal activity was higher in spring than in autumn. This suggests that the
      endogenous program responds to specific seasonal needs, with more time invested
      in storing fuel for a safe journey in autumn and more time invested in flying to
      reach the breeding grounds early in spring. Contrary to expectations, the timing
      of onset of body mass increase and nocturnal restlessness in spring did not
      differ between populations. This might be explained by the lack of external cues,
      most likely photoperiod, which are responsible for the fine tuning of the
      expression of migratory behavior.

PMID- 20679497
TI  - Light intensity determines temporal niche switching of behavioral activity in
      deep-water Nephrops norvegicus (Crustacea: Decapoda).
AB  - The temporal distribution of behavioral programs throughout the 24-h day, known
      as temporal niche of a species, is determined by ecological factors that directly
      affect the adaptive value of the timing of specific behaviors. Temporal niche
      switching has been described in several species and is likely adaptive in
      habitats where the daily timing of those factors changes. Benthic species whose
      habitats span a wide range of water depths are exposed to considerable depth
      dependent environmental changes. Temporally scheduled trawl surveys of the Norway
      lobster, Nephrops norvegicus, reveal that animals emerge from burrows at night on
      the shallow shelf (10-50 m deep), at crepuscular hours on the lower shelf (50-200
      m), and at daytime on the slope (200-400 m). The mechanisms underlying
      nocturnality/diurnality switches are chiefly unknown, and Nephrops offers a
      unique model for their study. The depth-dependent decrease in luminance is a
      likely candidate determining the temporal distribution of behavior. The authors
      explored this possibility in the laboratory by exposing Nephrops to light:dark
      (LD) cycles of 470-nm monochromatic lighting that mimic conditions at the 100-m
      deep shelf (10 lux) or the 300-m slope (0.1 lux). Two groups of animals were
      respectively exposed to each light intensity according to the following protocol:
      an initial 12:12 LD stage followed by constant darkness (DD), followed in turn by
      a second 12:12 LD stage. Activity at the burrow opening (door-keeping = DK), as
      well as full emergence (E), was continuously monitored. Under 10-lux LD cycles,
      most animals showed nocturnal DK activity-with some being crepuscular or diurnal
      and all animals showed nocturnal E activity. In contrast, both behaviors were
      clearly diurnal in animals under 0.1-lux LD cycles. The phase of the nocturnal
      and diurnal DK rhythms detected respectively at 10 and 0.1 lux upon release into
      DD revealed that these rhythms are entrained circadian rhythms. The present data
      indicate that nocturnality/diurnality switches in Nephrops in its natural
      habitat, evidenced by captures at different depths, are likely determined by
      light intensity. This temporal niche switching involves different patterns of
      photic entrainment, leading to bona fide circadian diurnal or nocturnal
      phenotypes, as well as exogenous masking of behavioral outputs.

PMID- 20679498
TI  - Sex differences in phase angle of entrainment and melatonin amplitude in humans.
AB  - Studies of sex differences in the timing of human circadian rhythms have reported
      conflicting results. This may be because the studies conducted to date have not
      controlled for the masking effects of the rest activity cycle on the circadian
      rhythms being assessed. In the present analysis of data collected under
      controlled conditions, we examined sex differences in the timing of circadian
      rhythms while minimizing masking from behavioral and environmental factors using
      a constant routine (CR) protocol. All participants (28 women and 28 men paired by
      habitual wake time; age range, 18 30 years) maintained a regular self selected
      sleep wake schedule at home prior to the study. After 3 baseline days in the
      laboratory, participants began a CR. Women were found to have a significantly
      higher melatonin amplitude and lower temperature amplitude than men. While sleep
      timing was the same between the 2 groups, the timing of the circadian rhythms of
      core body temperature and pineal melatonin secretion was earlier relative to
      sleep time in women as compared to men. Sleep therefore occurred at a later
      biological time for women than men, despite being at the same clock time. Given
      that sleep propensity and structure vary with circadian phase and are impacted by
      circulating melatonin, these findings may have important implications for
      understanding sex differences in sleep timing and duration, diurnal preference,
      and the prevalence of sleep disorders such as insomnia.

PMID- 20679499
TI  - Circadian rhythm phase advance with dawn simulation treatment for winter
      depression.

PMID- 20679500
TI  - In vitro P-glycoprotein interactions and steady-state pharmacokinetic
      interactions between tolvaptan and digoxin in healthy subjects.
AB  - Interactions between tolvaptan and digoxin were determined in an open-label,
      sequential study where 14 healthy subjects received tolvaptan 60 mg once daily
      (QD) on days 1 and 12 to 16 and digoxin 0.25 mg QD on days 5 to 16. Mean maximal
      concentrations (C(max)) and area under the curve during the dosing interval
      (AUC(tau)) for digoxin with tolvaptan (day 16) were increased 1.27- and 1.18-fold
      compared with digoxin alone (day 11); mean renal clearance of digoxin was
      decreased by 59% (P < .05). Tolvaptan C(max) and AUC(0-24h) for a single dose
      with digoxin (day 12) were each increased about 10% compared with tolvaptan alone
      (day 1). Tolvaptan did not accumulate upon multiple dosing. After a single dose
      of tolvaptan (day 1, day 12), 24-hour urine volume was about 7.5 L. As expected,
      after 5 days of tolvaptan, 24-hour urine volume decreased about 20%. In vitro
      studies in control and MDR1-expressing LLC-PK1 cells indicate that tolvaptan is a
      substrate of P-glycoprotein. Tolvaptan (50 uM) inhibited basolateral to apical
      digoxin secretion to the same extent as 30 uM verapamil; the IC50 of tolvaptan
      was determined to be 15.9 uM. The increase in steady-state digoxin concentrations
      is likely mediated by tolvaptan inhibition of digoxin secretion.

PMID- 20679501
TI  - Safety and pharmacokinetics of higher doses of caspofungin in healthy adult
      participants.
AB  - Caspofungin was the first in a new class of antifungal agents (echinocandins)
      indicated for the treatment of primary and refractory fungal infections. Higher
      doses of caspofungin may provide another option for patients who have failed
      caspofungin or other antifungal therapy. This study evaluated the safety,
      tolerability, and pharmacokinetics of single 150- and 210-mg doses of caspofungin
      in 16 healthy participants and 100 mg/d for 21 days in 20 healthy participants.
      Other than infusion site reactions and 1 reversible elevation in alanine
      aminotransferase (>=2* and <4* upper limit of normal), caspofungin was generally
      well tolerated. Geometric mean AUC(0-infinity) after single 150- and 210-mg doses
      was 279.7 and 374.9 ug.h/mL, respectively; peak concentrations were 29.4 and 33.5
      ug/mL, respectively; and 24-hour postdose concentrations were 2.8 and 4.2 ug/mL,
      respectively. Steady state was achieved in the third week of dosing. Following
      multiple 100-mg doses of caspofungin, day 21 geometric mean AUC(0-24) was 227.4
      ug.h/mL, peak concentration was 20.9 ug/mL, and trough concentration was 4.7
      ug/mL. Beta-phase t(1/2) was ~8 to ~13 hours. Caspofungin pharmacokinetics at
      these higher doses were dose proportional to and consistent with those observed
      at lower doses, suggesting a modest nonlinearity of increased accumulation with
      dose, which was considered not clinically meaningful.

PMID- 20679502
TI  - Organization of parent knowledge: compartmentalization and integration in adult
      child-parent relationships.
AB  - Previous research has demonstrated an association between structure of beliefs
      about romantic partners and feelings for that partner. Here, the structure of
      college students' beliefs about their parents was linked to distinct types of
      ongoing parent-child relationships identified by cluster analysis. An integrative
      structure of mother knowledge was associated with an evaluatively complex type of
      relationship ("dealing"), characterized by greater liking and closeness and less
      cooperation and contact. Positive compartmentalization of mother knowledge was
      associated with mother relationships that were consistently positive ("denying")
      across different dimensions. In contrast, the most positive father relationships
      were reported by daughters with evaluatively integrative father structures.
      Possible reasons for daughters' tendency to integrate father structures and to
      compartmentalize mother structures are discussed.

PMID- 20679503
TI  - Bioavailability and population pharmacokinetics of voriconazole in lung
      transplant recipients.
AB  - This study was undertaken to characterize the pharmacokinetics and
      bioavailability of voriconazole in adult lung transplant patients during the
      early postoperative period, identify factors significantly associated with
      various pharmacokinetic parameters, and make recommendations for adequate dosing
      regimens. Thirteen lung transplant patients received two intravenous infusions (6
      mg/kg, twice daily [b.i.d.]) immediately posttransplant followed by oral doses
      (200 mg, b.i.d.) for prophylaxis. Blood samples (9/interval) were collected
      during one intravenous and one oral dosing interval from each patient.
      Voriconazole plasma concentrations were measured by high-pressure liquid
      chromatography (HPLC). NONMEM was used to develop pharmacokinetic models,
      evaluate covariate relationships, and perform Monte Carlo simulations. There was
      a good correlation (R(2) = 0.98) between the area under the concentration-time
      curve specific for the dose evaluated (AUC(0-infinity)) and trough
      concentrations. A two-compartment model adequately described the data. Population
      estimates of bioavailability, clearance, V(c), and V(p) were 45.9%, 3.45
      liters/h, 54.7 liters, and 143 liters. Patients with cystic fibrosis (CF)
      exhibited a significantly lower bioavailability (23.7%, n = 3) than non-CF
      patients (63.3%, n = 10). Bioavailability increased with postoperative time and
      reached steady levels in about 1 week. V(p) increased with body weight.
      Bioavailability of voriconazole is substantially lower in lung transplant
      patients than non-transplant subjects but significantly increases with
      postoperative time. CF patients exhibit significantly lower bioavailability and
      exposure of voriconazole and therefore need higher doses. Intravenous
      administration of voriconazole during the first postoperative day followed by
      oral doses of 200 mg or 400 mg appeared to be the optimal dosing regimen.
      However, voriconazole levels should be monitored, and the dose should be
      individualized based on trough concentrations as a good measure of drug exposure.

PMID- 20679504
TI  - Origin and molecular evolution of the determinant of methicillin resistance in
      staphylococci.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most important
      multidrug-resistant pathogens around the world. MRSA is generated when
      methicillin-susceptible S. aureus (MSSA) exogenously acquires a methicillin
      resistance gene, mecA, carried by a mobile genetic element, staphylococcal
      cassette chromosome mec (SCCmec), which is speculated to be transmissible across
      staphylococcal species. However, the origin/reservoir of the mecA gene has
      remained unclear. Finding the origin/reservoir of the mecA gene is important for
      understanding the evolution of MRSA. Moreover, it may contribute to more
      effective control measures for MRSA. Here we report on one of the animal-related
      Staphylococcus species, S. fleurettii, as the highly probable origin of the mecA
      gene. The mecA gene of S. fleurettii was found on the chromosome linked with the
      essential genes for the growth of staphylococci and was not associated with
      SCCmec. The mecA locus of the S. fleurettii chromosome has a sequence practically
      identical to that of the mecA-containing region (~12 kbp long) of SCCmec.
      Furthermore, by analyzing the corresponding gene loci (over 20 kbp in size) of S.
      sciuri and S. vitulinus, which evolved from a common ancestor with that of S.
      fleurettii, the speciation-related mecA gene homologues were identified,
      indicating that mecA of S. fleurettii descended from its ancestor and was not
      recently acquired. It is speculated that SCCmec came into form by adopting the S.
      fleurettii mecA gene and its surrounding chromosomal region. Our finding suggests
      that SCCmec was generated in Staphylococcus cells living in animals by acquiring
      the intrinsic mecA region of S. fleurettii, which is a commensal bacterium of
      animals.

PMID- 20679505
TI  - Simple model for testing drugs against nonreplicating Mycobacterium tuberculosis.
AB  - Nonreplicating or dormant cells of Mycobacterium tuberculosis constitute a
      challenge to tuberculosis (TB) therapy because of their tolerance or phenotypic
      resistance to most drugs. Here, we propose a simple model for testing drugs
      against nongrowing cells that exploits the 18b strain of M. tuberculosis, a
      streptomycin (STR)-dependent mutant. Optimal conditions were established that
      allowed 18b cells to replicate in the presence of STR and to survive, but not
      multiply, following withdrawal of STR. In the presence of the antibiotic, M.
      tuberculosis 18b was susceptible to the currently approved TB drugs, isoniazid
      (INH) and rifampin (RIF), and to the experimental drugs TMC207, PA-824, meropenem
      (MER), benzothiazinone (BTZ), and moxifloxacin (MOXI). After STR depletion, the
      strain displayed greatly reduced susceptibility to the cell wall inhibitors INH
      and BTZ but showed increased susceptibility to RIF and PA-824, while MOXI and MER
      appeared equipotent under both conditions. The same potency ranking was found
      against nonreplicating M. tuberculosis 18b after in vivo treatment of chronically
      infected mice with five of these drugs. Despite the growth arrest, strain 18b
      retains significant metabolic activity in vitro, remaining positive in the
      resazurin reduction assay. Upon adaption to a 96-well format, this assay was
      shown to be suitable for high-throughput screening with strain 18b to find new
      inhibitors of dormant M. tuberculosis.

PMID- 20679506
TI  - Trypanocidal activity of aziridinyl nitrobenzamide prodrugs.
AB  - The trypanocidal agents nifurtimox and benznidazole both function as prodrugs and
      must undergo enzyme-mediated activation, a reaction catalyzed by type I
      nitroreductase (NTR). In the search for new parasitic therapies, we have utilized
      this finding to investigate whether aziridinyl nitrobenzamide derivatives have
      activity against bloodstream-form Trypanosoma brucei and Trypanosoma cruzi
      amastigotes, parasite stages that replicate in the mammalian host. For T. cruzi
      drug screening, we generated trypanosomes that expressed the luciferase reporter
      gene and optimized a mammalian infection model in a 96-well plate format. A
      subset of compounds having a 5-(aziridin-1-yl)-2,4-dinitrobenzyl structure was
      shown to be metabolized by purified T. brucei NTR and when screened against both
      parasite life cycle stages displayed significant growth-inhibitory properties:
      the most potent compounds generated 50% inhibitory concentrations of <1 MUM. The
      trypanocidal activity was shown to be NTR specific, since parasites
      overexpressing this enzyme were hypersensitive to the aziridinyl dinitrobenzyl
      agents. We conclude that members of the aziridinyl nitrobenzamide class of
      nitroheterocycles provide new lead structures that have the potential to treat
      trypanosomal infections.

PMID- 20679507
TI  - Membrane efflux and influx modulate both multidrug resistance and virulence of
      Klebsiella pneumoniae in a Caenorhabditis elegans model.
AB  - Cross-resistance to cefoxitin (FOX), chloramphenicol (CMP), and quinolones
      (nalidixic acid [NAL]) related to a putative efflux system overexpression has
      recently been reported for Klebsiella pneumoniae. The potential impact of this
      multidrug resistance (MDR) on the virulence of K. pneumoniae was evaluated in the
      Caenorhabditis elegans model. For 2 of the 3 MDR clinical isolates studied, a
      significant increase in acrB transcription was found in comparison with their
      antibiotic-susceptible revertants. ATCC 138821 and MDR, revertant, and derivative
      strains with altered porin expression were studied. Strains proved or suspected
      to overexpress an efflux system were significantly more virulent than the ATCC
      and revertant strains (time to kill 50% of nematodes [LT(50)] in days: 3.4 to 3.8
      +/- 0.2 versus 4.1 to 4.4 +/- 0.3, P < 0.001). Inversely, strains with altered
      porin expression were significantly less virulent, independently of the
      expression level of efflux system (LT(50) = 5.4 to 5.6 +/- 0.2, P < 0.001).
      Altered porin expression did not change MICs of CMP and NAL but did those of FOX
      (4 to 16* MIC) and ertapenem (16 to 64* MIC). The strains with a normally or an
      overexpressed efflux system that received the beta-lactamase CTX-M-15 became more
      widely resistant without modification of their virulence potential, suggesting
      that balance between resistance and virulence is dependent on the type of
      resistance mechanisms. In conclusion, this study shows that the expression of
      both efflux systems and porins is a key factor not only for antibiotic resistance
      but also virulence potential in K. pneumoniae.

PMID- 20679508
TI  - Reservoir of antimicrobial resistance determinants associated with horizontal
      gene transfer in clinical isolates of the genus Shewanella.

PMID- 20679509
TI  - Increased temperature enhances the antimicrobial effects of daptomycin,
      vancomycin, tigecycline, fosfomycin, and cefamandole on staphylococcal biofilms.
AB  - Implant-related infections are serious complications of trauma and orthopedic
      surgery and are most difficult to treat. The bacterial biofilms of 34 clinical
      Staphylococcus sp. isolates (Staphylococcus aureus, n = 14; coagulase-negative
      staphylococci, n = 19) were incubated with daptomycin (DAP; 5, 25, or 100
      mg/liter), vancomycin (VAN; 5, 25, or 100 mg/liter), tigecycline (TGC; 1, 5, or
      25 mg/liter), fosfomycin (FOM; 100, 250, or 1,000 mg/liter), and cefamandole
      (FAM; 50, 100, or 500 mg/liter) for 24 h at three different ambient temperatures:
      35 degrees C, 40 degrees C, and 45 degrees C. To quantify the reduction of the
      biomass, the optical density ratio (ODr) of stained biofilms and the number of
      growing bacteria were determined. Increasing the temperature to 45 degrees C or
      to 40 degrees C during incubation with FAM, FOM, TGC, VAN, or DAP led to a
      significant but differential reduction of the thickness of the staphylococcal
      biofilms compared to that at 35 degrees C (P < 0.05). Growth reduction was
      enhanced for DAP at 100 mg/liter at 35 degrees C, 40 degrees C, and 45 degrees C
      (log count reductions, 4, 3.6, and 3.3, respectively; P < 0.05). A growth
      reduction by 2 log counts was detected for FAM at a concentration of 500 mg/liter
      at 40 degrees C and 45 degrees C (P = 0.01). FOM at 1,000 mg/liter reduced the
      bacterial growth by 1.2 log counts (not significant). The antibacterial activity
      of antimicrobial agents is significantly but differentially enhanced by
      increasing the ambient temperature and using high concentrations. Adjuvant
      hyperthermia may be of value in the treatment of biofilm-associated implant
      related infections.

PMID- 20679511
TI  - A retrospective evaluation of pretreatment and follow-up monitoring of HIV
      infected adult patients in a resource-poor setting.
AB  - The rapid scale-up of antiretroviral therapy (ART) is associated with the
      challenges of ensuring that HIV care delivered to clients is of the highest
      quality. This study was designed to evaluate the pretreatment and 12 month follow
      up monitoring of clinical and laboratory profiles of HIV-infected patients at the
      adult HIV clinic of the University of Ilorin Teaching Hospital, in Nigeria. It
      was a retrospective analysis of records of 440 adult patients who were on follow
      up visits for 1 or more years. Two hundred two (45.9%) were male and 238 (54.1%)
      were female. Weight was documented at baseline in 314 (71.4%) and at month 12 of
      follow-up in 258 (58.6%). Baseline World Health Organization (WHO) clinical stage
      was documented in 269 (61.1%). Baseline CD4 count, full blood count (FBC),
      creatinine (Cr), liver function tests (LFT), fasting blood sugar (FBS), and
      fasting serum lipids (FSL) were documented in 243 (55.6%), 260 (59.1%), 143
      (32.5%), 136 (30.9%), 268 (60.9%), and 161 (36.6%), respectively. At 12th month
      of follow-up visit, the CD4 count, FBC, Cr, LFT, FBS, and FSL were documented in
      121 (27.5%), 94 (21.4%), 59 (13.4%), 77 (17.5%), 179 (40.7%), and 95 (21.6%),
      respectively. This report shows that the pretreatment and the 12th-month follow
      up monitoring of HIV-infected adult patients in our center was less than optimal.
      We recommend periodic self-assessment by care providers to monitor compliance
      with standards.

PMID- 20679510
TI  - Genetic determinants involved in the susceptibility of Pseudomonas aeruginosa to
      beta-lactam antibiotics.
AB  - The resistome of P. aeruginosa for three beta-lactam antibiotics, namely,
      ceftazidime, imipenem, and meropenem, was deciphered by screening a comprehensive
      PA14 mutant library for mutants with increased or reduced susceptibility to these
      antimicrobials. Confirmation of the phenotypes of all selected mutants was
      performed by Etest. Of the total of 78 confirmed mutants, 41 demonstrated a
      reduced susceptibility phenotype and 37 a supersusceptibility (i.e., altered
      intrinsic resistance) phenotype, with 6 mutants demonstrating a mixed phenotype,
      depending on the antibiotic. Only three mutants demonstrated reduced (PA0908) or
      increased (glnK and ftsK) susceptibility to all three antibiotics. Overall, the
      mutant profiles of susceptibility suggested distinct mechanisms of action and
      resistance for the three antibiotics despite their similar structures. More
      detailed analysis indicated important roles for novel and known beta-lactamase
      regulatory genes, for genes with likely involvement in barrier function, and for
      a range of regulators of alginate biosynthesis.

PMID- 20679512
TI  - IL-1 plays an important role in the bone metabolism under physiological
      conditions.
AB  - It is well known that IL-1 is involved in bone resorption under pathological
      conditions. The role of this cytokine in bone remodeling under physiological
      conditions, however, remains obscure. In this study, we addressed the role of IL
      1 in physiological bone metabolism through analyses of IL-1alpha-deficient (KO),
      IL-1beta KO and IL-1alpha/beta double KO mice that were housed under specific
      pathogen free conditions. The femur mineral density, trabecular bone mass and
      cortical thickness significantly increased in all KO mice compared with wild-type
      (WT) mice. The number of osteoclasts in trabecular bones decreased, suggesting
      that IL-1 regulates bone metabolism through regulation of osteoclast formation.
      When differentiation of bone marrow (BM) cells into osteoclasts was induced by
      parathyroid hormone in co-cultures of osteoblasts and BM cells from WT and IL
      1alpha/beta KO mice, IL-1alpha/beta KO BM cell co-cultures failed to undergo
      efficient osteoclast-like multinucleated cell (OCL) differentiation, although
      high levels of receptor activator of nuclear factor-kappaB (NF-kappaB) ligand
      (RANKL) was induced. In contrast, efficient OCL differentiation was observed in
      IL-1alpha/beta KO osteoblast/WT BM cell co-cultures, in which high levels of IL
      1alpha/beta and low levels of RANKL were produced. Addition of IL-1alpha to IL
      1alpha/beta KO BM-derived macrophage cultures markedly enhanced OCL
      differentiation induced by soluble RANKL, and the downstream molecules of
      receptor activator of NF-kappaB (RANK) including c-Jun N-terminal factor,
      extracellular signal-regulated kinase and c-Fos were less activated in the
      absence of IL-1 upon treatment with RANKL. Taken together, these results indicate
      that IL-1 directly activates RANK signaling other than inducing RANKL to promote
      osteoclastogenesis and plays an important role in physiological bone metabolism.

PMID- 20679513
TI  - Targeting ganglioside epitope 3G11 on the surface of CD4+ T cells suppresses EAE
      by altering the Treg/Th17 cell balance.
AB  - Loss of expression of the 3G11 epitope, present on disialoceramide that is
      predominantly found on CD4(+) T cells, has been associated with a regulatory T
      cell (Treg) phenotype and tolerance induction in experimental autoimmune
      encephalomyelitis (EAE). Here we report that treatment with anti-3G11 mAb shifts
      the immune response from pro-inflammatory to tolerogenic and suppresses both
      chronic-progressive and relapsing-remitting EAE. This therapeutic effect can be
      achieved at different stages of EAE. Treatment with anti-3G11 mAb increased the
      proportion of Foxp3(+)CD25(+)CD4(+) Tregs and IL-10 production while inhibiting
      production of pro-inflammatory cytokines and responsiveness to IL-2 and
      decreasing the proportion of T(h)17 cells. The effect of anti-3G11 mAb was
      diminished in IL-10(-/-) mice, indicating that this cytokine mediates some of its
      effects. As 3G11 belongs to the ganglioside family, which is expressed on the
      surface of both murine and human CD4(+) T cells, targeting this class of
      molecules may provide a novel approach for treating autoimmune diseases.

PMID- 20679515
TI  - Promoter strength influences the S phase requirement for establishment of
      silencing at the Saccharomyces cerevisiae silent mating type Loci.
AB  - In Saccharomyces cerevisiae, the two cryptic mating type loci, HML and HMR, are
      transcriptionally silent. Previous studies on the establishment of silencing at
      HMR identified a requirement for passage through S phase. However, the underlying
      mechanism for this requirement is still unknown. In contrast to HMR, we found
      that substantial silencing of HML could be established without passage through S
      phase. To understand this difference, we analyzed several chimeric HM loci and
      found that promoter strength determined the S phase requirement. To silence a
      locus with a strong promoter such as the a1/a2 promoter required passage through
      S phase while HM loci with weaker promoters such as the alpha1/alpha2 or TRP1
      promoter did not show this requirement. Thus, transcriptional activity
      counteracts the establishment of silencing but can be overcome by passage through
      S phase.

PMID- 20679514
TI  - A two-pathway analysis of meiotic crossing over and gene conversion in
      Saccharomyces cerevisiae.
AB  - Several apparently paradoxical observations regarding meiotic crossing over and
      gene conversion are readily resolved in a framework that recognizes the existence
      of two recombination pathways that differ in mismatch repair, structures of
      intermediates, crossover interference, and the generation of noncrossovers. One
      manifestation of these differences is that simultaneous gene conversion on both
      sides of a recombination-initiating DNA double-strand break ("two-sidedness")
      characterizes only one of the two pathways and is promoted by mismatch repair.
      Data from previous work are analyzed quantitatively within this framework, and a
      molecular model for meiotic double-strand break repair based on the concept of
      sliding D-loops is offered as an efficient scheme for visualizing the salient
      results from studies of crossing over and gene conversion, the molecular
      structures of recombination intermediates, and the biochemical competencies of
      the proteins involved.

PMID- 20679516
TI  - Sex peptide is required for the efficient release of stored sperm in mated
      Drosophila females.
AB  - The Drosophila seminal fluid protein (SFP) sex peptide (SP) elicits numerous post
      mating responses, including increased egg laying and decreased sexual
      receptivity, in the mated female. Unlike other SFPs, which are detectable in
      mated females for only a few hours post mating, SP is maintained-and its effects
      are sustained-for several days. The persistence of SP in the mated female's
      reproductive tract is thought to be a consequence of its binding to, and gradual
      release from, sperm in storage, which maintains SP's ability to act within the
      female reproductive tract. Recent studies have shown that several other SFPs,
      acting in a network, are needed for SP's localization to sperm and are necessary
      for the efficient release of sperm from storage. This result suggested an
      additional new role for SP modulating the release of sperm from storage. We
      tested for this possibility by examining sperm storage parameters in mated
      females that did not receive SP. We found that while sperm accumulation into
      storage was unaffected, sperm depletion from storage sites was significantly
      decreased (or impaired) in the absence of SP. Mates of males expressing a
      modified SP that is unable to be released from sperm showed a similar phenotype,
      indicating that release of sperm-bound SP is a necessary component of normal
      sperm depletion. Additionally, SP null males were more successful in a sperm
      competitive environment when they were first to mate, which is likely a
      consequence of higher retention of their sperm due to defective sperm release.
      Our findings illustrate a direct role for SP in the release of sperm from
      storage.

PMID- 20679517
TI  - Genomic admixture analysis in European Populus spp. reveals unexpected patterns
      of reproductive isolation and mating.
AB  - Admixture between genetically divergent populations facilitates genomic studies
      of the mechanisms involved in adaptation, reproductive isolation, and speciation,
      including mapping of the loci involved in these phenomena. Little is known about
      how pre- and postzygotic barriers will affect the prospects of "admixture
      mapping" in wild species. We have studied 93 mapped genetic markers
      (microsatellites, indels, and sequence polymorphisms, ~60,000 data points) to
      address this topic in hybrid zones of Populus alba and P. tremula, two
      widespread, ecologically important forest trees. Using genotype and linkage
      information and recently developed analytical tools we show that (1) reproductive
      isolation between these species is much stronger than previously assumed but this
      cannot prevent the introgression of neutral or advantageous alleles, (2)
      unexpected genotypic gaps exist between recombinant hybrids and their parental
      taxa, (3) these conspicuous genotypic patterns are due to assortative mating and
      strong postzygotic barriers, rather than recent population history. We discuss
      possible evolutionary trajectories of hybrid lineages between these species and
      outline strategies for admixture mapping in hybrid zones between highly divergent
      populations. Datasets such as this one are still rare in studies of natural
      hybrid zones but should soon become more common as high throughput genotyping and
      resequencing become feasible in nonmodel species.

PMID- 20679518
TI  - Regulation of jaw-specific isoforms of myosin-binding protein-C and tropomyosin
      in regenerating cat temporalis muscle innervated by limb fast and slow motor
      nerves.
AB  - Cat jaw-closing muscles are a distinct muscle allotype characterized by the
      expression of masticatory-specific myofibrillar proteins. Transplantation studies
      showed that expression of masticatory myosin heavy chain (m-MyHC) is promoted by
      fast motor nerves, but suppressed by slow motor nerves. We investigated whether
      masticatory myosin-binding protein-C (m-MBP-C) and masticatory tropomyosin (m-Tm)
      are similarly regulated. Temporalis muscle strips were transplanted into limb
      muscle beds to allow innervation by fast or slow muscle nerve during
      regeneration. Regenerated muscles were examined postoperatively up to 168 days by
      peroxidase IHC using monoclonal antibodies to m-MyHC, m-MBP-C, and m-Tm.
      Regenerates in both muscle beds expressed fetal and slow MyHCs, m-MyHC, m-MBP-C,
      and m-Tm during the first 4 weeks. Longer-term regenerates innervated by fast
      nerve suppressed fetal and slow MyHCs, retaining m-MyHC, m-MBP-C, and m-Tm,
      whereas fibers innervated by slow nerve suppressed fetal MyHCs and the three
      masticatory-specific proteins, induced slow MyHC, and showed immunohistochemical
      characteristics of jaw-slow fibers. We concluded that expression of m-MBP-C and m
      Tm is coregulated by m-MyHC and that neural impulses to limb slow muscle are
      capable of suppressing masticatory-specific proteins and to channel gene
      expression along the jaw-slow phenotype unique to jaw-closing muscle.

PMID- 20679519
TI  - Distribution of small integrin-binding ligand, N-linked glycoproteins (SIBLING)
      in the articular cartilage of the rat femoral head.
AB  - The small integrin-binding ligand, N-linked glycoprotein (SIBLING) family is
      closely related to osteogenesis. Until recently, little was known about their
      existence in articular cartilage. In this study, we systematically evaluated the
      presence and distribution of four SIBLING family members in rat femoral head
      cartilage: dentin matrix protein 1 (DMP1), bone sialoprotein (BSP), osteopontin
      (OPN), and dentin sialophosphoprotein (DSPP). First, non-collagenous proteins
      were extracted and then separated by ion-exchange chromatography. Next, the
      protein extracts eluted by chromatography were analyzed by Stains-all staining
      and Western immunoblotting. IHC was used to assess the distribution of these four
      SIBLING family members in the femoral head cartilage. Both approaches showed that
      all the four SIBLING family members are expressed in the femoral head cartilage.
      IHC showed that SIBLING members are distributed in various locations throughout
      the articular cartilage. The NH2-terminal fragments of DMP1, BSP, and OPN are
      present in the cells and in the extracellular matrix, whereas the COOH-terminal
      fragment of DMP1 and the NH2-terminal fragment of DSPP are primarily
      intracellularly localized in the chondrocytes. The presence of the SIBLING family
      members in the rat femoral head cartilage suggests that they may play important
      roles in chondrogenesis.

PMID- 20679521
TI  - Family background buys an education in Minnesota but not in Sweden.
AB  - Educational attainment, the highest degree or level of schooling obtained, is
      associated with important life outcomes, at both the individual level and the
      group level. Because of this, and because education is expensive, the allocation
      of education across society is an important social issue. A dynamic quantitative
      environmental-genetic model can help document the effects of social allocation
      patterns. We used this model to compare the moderating effect of general
      intelligence on the environmental and genetic factors that influence educational
      attainment in Sweden and the U.S. state of Minnesota. Patterns of genetic
      influence on educational outcomes were similar in these two regions, but patterns
      of shared environmental influence differed markedly. In Sweden, shared
      environmental influence on educational attainment was particularly important for
      people of high intelligence, whereas in Minnesota, shared environmental
      influences on educational attainment were particularly important for people of
      low intelligence. This difference may be the result of differing access to
      education: state-supported access (on the basis of ability) to a uniform higher
      education system in Sweden versus family-supported access to a more diverse
      higher-education system in the United States.

PMID- 20679522
TI  - Do decisions shape preference? Evidence from blind choice.
AB  - Psychologists have long asserted that making a choice changes a person's
      preferences. Recently, critics of this view have argued that choosing simply
      reveals preexisting preferences, and that all studies claiming that choice shapes
      preferences suffer from a fundamental methodological flaw. Here we address this
      question directly by dissociating preexisting preferences from decision making.
      We studied participants who rated different vacation destinations both before and
      after making a blind choice that could not be guided by preexisting preferences.
      As an additional control, we elicited ratings in a condition in which a computer
      made the decision for the participants. We found that preferences were altered
      after participants made a blind choice, but not after a computer dictated the
      decision. The results suggest that just as preferences form choices, choices
      shape preferences.

PMID- 20679523
TI  - Synchronous multisensory stimulation blurs self-other boundaries.
AB  - In a study that builds on recent cognitive neuroscience research on body
      perception and social psychology research on social relations, we tested the
      hypothesis that synchronous multisensory stimulation leads to self-other merging.
      We brushed the cheek of each study participant as he or she watched a stranger's
      cheek being brushed in the same way, either in synchrony or in asynchrony. We
      found that this multisensory procedure had an effect on participants' body
      perception as well as social perception. Study participants exposed to
      synchronous stimulation showed more merging of self and the other than
      participants exposed to asynchronous stimulation. The degree of self-other
      merging was determined by measuring participants' body sensations and their
      perception of face resemblance, as well as participants' judgment of the inner
      state of the other, closeness felt toward the other, and conformity behavior. The
      results of this study show how multisensory integration can affect social
      perception and create a sense of self-other similarity.

PMID- 20679524
TI  - Eye movements during mindless reading.
AB  - Mindless reading occurs when the eyes continue moving across the page even though
      the mind is thinking about something unrelated to the text. Despite how commonly
      it occurs, very little is known about mindless reading. The present experiment
      examined eye movements during mindless reading. Comparisons of fixation-duration
      measures collected during intervals of normal reading and intervals of mindless
      reading indicate that fixations during the latter were longer and less affected
      by lexical and linguistic variables than fixations during the former. Also, eye
      movements immediately preceding self-caught mind wandering were especially
      erratic. These results suggest that the cognitive processes that guide eye
      movements during normal reading are not engaged during mindless reading. We
      discuss the implications of these findings for theories of eye movement control
      in reading, for the distinction between experiential awareness and meta
      awareness, and for reading comprehension.

PMID- 20679525
TI  - Closed headpiece of integrin alphaIIbbeta3 and its complex with an alphaIIbbeta3
      specific antagonist that does not induce opening.
AB  - The platelet integrin alpha(IIb)beta(3) is essential for hemostasis and
      thrombosis through its binding of adhesive plasma proteins. We have determined
      crystal structures of the alpha(IIb)beta(3) headpiece in the absence of ligand
      and after soaking in RUC-1, a novel small molecule antagonist. In the absence of
      ligand, the alpha(IIb)beta(3) headpiece is in a closed conformation, distinct
      from the open conformation visualized in presence of Arg-Gly-Asp (RGD)
      antagonists. In contrast to RGD antagonists, RUC-1 binds only to the alpha(IIb)
      subunit. Molecular dynamics revealed nearly identical binding. Two species
      specific residues, alpha(IIb) Y190 and alpha(IIb) D232, in the RUC-1 binding site
      were confirmed as important by mutagenesis. In sharp contrast to RGD-based
      antagonists, RUC-1 did not induce alpha(IIb)beta(3) to adopt an open
      conformation, as determined by gel filtration and dynamic light scattering. These
      studies provide insights into the factors that regulate integrin headpiece
      opening, and demonstrate the molecular basis for a novel mechanism of integrin
      antagonism.

PMID- 20679526
TI  - Recurrent expression signatures of cytokines and chemokines are present and are
      independently prognostic in acute myelogenous leukemia and myelodysplasia.
AB  - The role of circulating cytokines and chemokines (C&Ckine) in activating signal
      transduction in leukemic cells is incompletely defined. We hypothesized that
      comprehensive profiling of C&Ckine expression in leukemia would provide greater
      insight compared with individual analyses. We used multiplex array technology to
      simultaneously measure the level of 27 C&Ckines in serum from 176 acute
      myelogenous leukemia (AML) and 114 myelodysplastic syndrome (MDS) patients and 19
      normal controls. C&Ckine levels in AML and MDS differed significantly from normal
      controls (5 higher, 13 lower) but were similar to each other for 24 of 27
      analytes, with interleukin-8 and interleukin-13 higher in AML and vascular
      endothelial growth factor A higher in MDS. Levels did not correlate with age,
      gender, infection, or blood counts; however, 3 correlated with specific
      cytognetic abnormalities in AML. Individually, few cytokines had any correlation
      with response or survival. In newly diagnosed AML, 8 C&Ckine signatures, distinct
      from the normal control signature, were observed. These signatures had prognostic
      impact, affecting remission, primary resistance, relapse rates, and overall
      survival, individually (P = .003) and in multivariable analysis (P = .004). These
      patterns suggest specific therapeutic interventions to investigate in subsets of
      AML patients. In conclusion, C&Ckine expression in AML and MDS differs from
      normal, is similar with one another, and forms recurrent patterns of expression
      with prognostic relevance.

PMID- 20679527
TI  - In anemia of multiple myeloma, hepcidin is induced by increased bone
      morphogenetic protein 2.
AB  - Hepcidin is the principal iron-regulatory hormone and a pathogenic factor in
      anemia of inflammation. Patients with multiple myeloma (MM) frequently present
      with anemia. We showed that MM patients had increased serum hepcidin, which
      inversely correlated with hemoglobin, suggesting that hepcidin contributes to MM
      related anemia. Searching for hepcidin-inducing cytokines in MM, we quantified
      the stimulation of hepcidin promoter-luciferase activity in HuH7 cells by MM
      sera. MM sera activated the hepcidin promoter significantly more than did normal
      sera. We then examined the role of bone morphogenetic proteins (BMPs) and
      interleukin-6 (IL-6), the major transcriptional regulators of hepcidin. Mutations
      in both BMP-responsive elements abrogated the activation dramatically, while
      mutations in the IL-6-responsive signal transducer and activator of transcription
      3-binding site (STAT3-BS) had only a minor effect. Cotreatment with anti-BMP-2/4
      or noggin-Fc blocked the promoter induction with all MM sera, anti-IL-6 blocked
      it with a minority of sera, whereas anti-BMP-4, -6, or -9 antibodies had no
      effect. BMP-2-immunodepleted MM sera had decreased promoter stimulatory capacity,
      and BMP-2 concentrations in MM sera were significantly higher than in normal
      sera. Our results demonstrate that BMP-2 is a major mediator of the hepcidin
      stimulatory activity of MM sera.

PMID- 20679529
TI  - NK cells as effectors of acquired immune responses: effector CD4+ T cell
      dependent activation of NK cells following vaccination.
AB  - We characterized vaccine-induced cellular responses to rabies virus in naive
      adult volunteers. Contrary to current paradigms, we observed potent and prolonged
      in vitro NK cell cytokine production and degranulation responses after
      restimulation of PBMCs with inactivated rabies virus in vaccinated, but not in
      unvaccinated, individuals. This "recall" NK cell response was absolutely
      dependent on Ag-specific IL-2 from CD45RO(+) CD4(+) T cells as well as IL-12 and
      IL-18 from accessory cells. Importantly, NK cells represented over 70% of all IFN
      gamma-secreting and degranulating cells in the first 12-18 h after virus
      rechallenge indicating they may be required for rapid control of infection after
      vaccination. Activation of NK cells may be a critical function of IL-2-secreting
      effector memory T cells. Although IL-2-dependent postvaccination NK cell
      activation has been reported previously, this is the first time the magnitude of
      this effect and its contribution to the overall vaccine-induced response has been
      appreciated and the mechanisms of NK activation postvaccination have been
      elucidated. Our data will allow standard protocols for evaluating vaccine-induced
      immunity to be adapted to assess NK cell effector responses.

PMID- 20679528
TI  - Long-term prognostic significance of early molecular response to imatinib in
      newly diagnosed chronic myeloid leukemia: an analysis from the International
      Randomized Study of Interferon and STI571 (IRIS).
AB  - This study examines the prognostic significance of early molecular response using
      an expanded dataset in chronic myeloid leukemia patients enrolled in the
      International Randomized Study of Interferon and STI571 (IRIS). Serial molecular
      studies demonstrate decreases in BCR-ABL transcripts over time. Analyses of event
      free survival (EFS) and time to progression to accelerated phase/blast crisis
      (AP/BC) at 7 years were based on molecular responses using the international
      scale (IS) at 6-, 12-, and 18-month landmarks. Patients with BCR-ABL transcripts
      > 10% at 6 months and > 1% at 12 months had inferior EFS and higher rate of
      progression to AP/BC compared with all other molecular response groups.
      Conversely, patients who achieved major molecular response [MMR: BCR-ABL (IS) <=
      0.1%] by 18 months enjoyed remarkably durable responses, with no progression to
      AP/BC and 95% EFS at 7 years. The probability of loss of complete cytogenetic
      response by 7 years was only 3% for patients in MMR at 18 months versus 26% for
      patients with complete cytogenetic response but not MMR (P < .001). This study
      shows a strong association between the degree to which BCR-ABL transcript numbers
      are reduced by therapy and long-term clinical outcome, supporting the use of time
      dependent molecular measures to determine optimal response to therapy. This study
      is registered at www.clinicaltrials.gov as NCT00006343.

PMID- 20679530
TI  - Neutrophils influence the level of antigen presentation during the immune
      response to protein antigens in adjuvants.
AB  - Neutrophils modulated Ag presentation following immunization with Ags in CFA or
      IFA or alum. The neutrophils had an important negative role in the CD4 T cell and
      B cell responses to three protein Ags: hen egg white lysozyme, OVA, and
      listeriolysin O. In their absence (by depleting with Abs for only the first 24 h,
      or using genetically neutropenic mice), the cellular responses increased several
      fold. The CD8 response was not affected or slightly decreased. Competition for Ag
      between the presenting cells and the neutrophils, as well as an effect on the
      response to Ag-bearing dendritic cells (DCs), was documented. Neutrophils entered
      the draining lymph nodes rapidly and for a brief period of several hours,
      localizing mainly to the marginal sinus and superficial cortex. There they
      established brief contact with DCs and macrophages. Moreover, neutrophils
      imprinted on the quality of the subsequent DC-T cell interactions, despite no
      physical contact with them; by intravital microscopy, the clustering of Ag
      specific T cells and DCs was improved in neutropenic mice. Thus, neutrophils are
      obligate cells that briefly enter sites of immunization and set the level of Ag
      presentation. A brief depletion may have a considerably positive impact on
      vaccination.

PMID- 20679531
TI  - Activation of the ancestral polarity regulator protein kinase C zeta at the
      immunological synapse drives polarization of Th cell secretory machinery toward
      APCs.
AB  - A key feature in T lymphocyte biology is that Th cells rapidly polarize their
      secretory machinery toward cognate APCs. The molecular mechanisms of these
      dynamic Th cell responses and their impact on APC biology remain to be
      elucidated. In this study, we demonstrate that protein kinase Czeta (PKCzeta) is
      rapidly activated at the immunological synapse (IS) in human Th cells interacting
      with cognate dendritic cells (DCs) and that a functional PKCzeta is required for
      the polarization of Th cell secretory machinery toward DCs. We also show that
      PKCzeta-dependent Th cell polarization allows dedicated delivery of IFN-gamma and
      CD40L at the IS and is required for the activation of cognate DCs to IL-12
      production. PKCzeta synaptic activation is a low-threshold phenomenon and, in Th
      cells interacting with multiple DCs, selectively occurs at the IS formed with the
      DCs offering the strongest stimulus leading to dedicated Th cell polarization.
      Our results identify the PKCzeta signaling pathway as a key component of the Th
      cell polarization machinery and provide a molecular basis for T cell-dedicated
      activation of cognate DCs.

PMID- 20679532
TI  - Cutting edge: mutation of Francisella tularensis mviN leads to increased
      macrophage absent in melanoma 2 inflammasome activation and a loss of virulence.
AB  - The mechanisms by which the intracellular pathogen Francisella tularensis evades
      innate immunity are not well defined. We have identified a gene with homology to
      Escherichia coli mviN, a putative lipid II flippase, which F. tularensis uses to
      evade activation of innate immune pathways. Infection of mice with a F.
      tularensis mviN mutant resulted in improved survival and decreased bacterial
      burdens compared to infection with wild-type F. tularensis. The mviN mutant also
      induced increased absent in melanoma 2 inflammasome-dependent IL-1beta secretion
      and cytotoxicity in macrophages. The compromised in vivo virulence of the mviN
      mutant depended upon inflammasome activation, as caspase 1- and apoptosis
      associated speck-like protein containing a caspase recruitment domain-deficient
      mice did not exhibit preferential survival following infection. This study
      demonstrates that mviN limits F. tularensis-induced absent in melanoma 2
      inflammasome activation, which is critical for its virulence in vivo.

PMID- 20679533
TI  - Dendritic cell modification of neutrophil responses to infection after burn
      injury.
AB  - Burn patients are highly susceptible to infections due to increased exposure
      through wounds and impairments in a number of immune functions. Dendritic cells
      (DCs) are important in activation of numerous immune responses that are essential
      for the clearance of infections. We have found that prophylactic treatment of
      burn-injured mice with the DC growth factor FLT3 ligand (FL) significantly
      increases resistance to burn wound infections in a DC-dependent manner that is
      correlated closely with enhanced bacterial clearance. However, as DCs are not
      typically microbicidal, the mechanisms by which DC modulation enhances bacterial
      clearance are not known. Due to the rapid response of neutrophils to cutaneous
      wounds, and the reported interactions between DCs and neutrophils, we
      investigated the role of neutrophils in FL-mediated resistance to burn wound
      infection. This was examined both in vivo and in vitro through neutrophil
      depletion, supplementation of neutrophils, and assessment of neutrophil
      chemotaxis following FL treatment. To test the involvement of DCs, CD11c
      diphtheria toxin receptor transgenic mice were used to deplete DCs during FL
      treatment. Studies revealed that neutrophils do play a critical role in FL
      mediated resistance to a burn wound infection. Additionally, treatment with FL
      after a burn injury enhances neutrophil-mediated control of bacterial spread,
      neutrophil migratory capacity, and myeloperoxidase production in a DC-dependent
      manner. The results of this study provide new insight into immunological
      mechanisms that can offer protection against infection after burn injury.

PMID- 20679534
TI  - Cutting edge: all-trans retinoic acid sustains the stability and function of
      natural regulatory T cells in an inflammatory milieu.
AB  - Recent studies have demonstrated that plasticity of naturally occurring
      CD4(+)Foxp3(+) regulatory T cells (nTregs) may account for their inability to
      control chronic inflammation in established autoimmune diseases. All-trans
      retinoic acid (atRA), the active derivative of vitamin A, has been demonstrated
      to promote Foxp3(+) Treg differentiation and suppress Th17 development. In this
      study, we report a vital role of atRA in sustaining the stability and
      functionality of nTregs in the presence of IL-6. We found that nTregs treated
      with atRA were resistant to Th17 and other Th cell conversion and maintained
      Foxp3 expression and suppressive activity in the presence of IL-6 in vitro. atRA
      decreased IL-6R expression and signaling by nTregs. Of interest, adoptive
      transfer of nTregs even from arthritic mice treated with atRA suppressed
      progression of established collagen-induced arthritis. We suggest that nTregs
      treated with atRA may represent a novel treatment strategy to control established
      chronic immune-mediated inflammatory diseases.

PMID- 20679536
TI  - Ral isoforms are implicated in Fc gamma R-mediated phagocytosis: activation of
      phospholipase D by RalA.
AB  - Phagocytosis is an essential element of the immune response permitting the
      elimination of pathogens, cellular debris, apoptotic cells, and tumor cells.
      Recently, both phospholipase D (PLD) isoforms, PLD1 and PLD2, were shown to be
      necessary for efficient FcgammaR-mediated phagocytosis. In this study, we
      investigated the role of a potential PLD regulator, the Ral GTPases RalA and
      RalB, in murine RAW 264.7 macrophages. Both Ral isoforms are expressed in
      macrophages and are transiently activated following FcgammaR stimulation. When
      Ral expression levels were varied using Ral mutants or interference RNA,
      phagocytosis assays revealed that Ral isoforms have antagonistic effects; RalA is
      a positive modulator, whereas RalB plays a negative role. We then focused on RalA
      and its possible relationship with PLD. The increase in PLD activity that occurs
      when phagocytosis is stimulated was inhibited in cells with reduced RalA protein,
      but it was unaffected by reduced levels of RalB. Furthermore, in macrophages
      transfected with dsRed-RalA and GFP-PLD1 or GFP-PLD2, RalA colocalized with PLD1
      and PLD2 at the phagocytic cup during phagosome formation. Additional results
      obtained from immunoprecipitation of PLD from macrophages transfected with myc
      RalA and hemagglutinin-tagged PLD1 or PLD2 indicated an enhanced interaction of
      RalA with both PLD isoforms during phagocytic stimulation. The increase in RalA
      and PLD1 interaction was transient and correlated with the time course of RalA
      activation. These findings reveal a novel pathway involving RalA and PLD in the
      regulation of FcgammaR-mediated phagocytosis.

PMID- 20679535
TI  - A proinflammatory role for proteolytically cleaved annexin A1 in neutrophil
      transendothelial migration.
AB  - Neutrophil extravasation, a critical component of innate immunity must be tightly
      regulated to prevent inadvertent or prolonged inflammation and subsequent tissue
      damage. We have shown previously that endothelial ERK1/2 signaling essential for
      neutrophil transendothelial migration is induced by a soluble factor produced by
      activated neutrophils. In this study, we demonstrate that the soluble neutrophil
      factor is a truncated form of annexin A1 (AnxA1) that can be generated by calpain
      1 cleavage of the N terminus, thus identifying a novel proinflammatory function
      to AnxA1. In contrast, neither the full-length protein nor the N-terminal 26 aa
      peptide, previously shown to be antiinflammatory, were able to activate Erk. Our
      data suggest that two different fragments of AnxA1 have opposing functions in
      inflammation. We also provide evidence that C-terminal AnxA1 functions by
      increasing ICAM1 clustering around adherent neutrophils to anchor them to the
      endothelium and promote transmigration through the transcellular route.

PMID- 20679537
TI  - What if!

PMID- 20679538
TI  - Non-small cell lung cancer.

PMID- 20679539
TI  - Operative techniques in early-stage lung cancer.
AB  - Lung cancer is the most common cause of death by malignancy, responsible for more
      deaths than the next 4 causes combined and predicted to account for nearly
      220,000 new cancer diagnoses and 160,000 deaths in 2009. The cornerstone of
      therapy for early-stage lung cancer is lobectomy and mediastinal lymph node
      dissection. Although lobectomy is considered the standard procedure,
      segmentectomy may be appropriate for selected patients. Conventional approaches
      to resection may be used, including posterolateral and muscle-sparing
      thoracotomy. However, minimally invasive lobectomy and segmentectomy procedures
      are now commonly used with superior outcomes.

PMID- 20679540
TI  - Maintenance chemotherapy in non-small cell lung cancer.
AB  - Recent trials have shown a benefit with maintenance therapy after 4 to 6 cycles
      of chemotherapy. These trials have shown improvement in progression-free survival
      using agents approved as second-line therapy in non-small cell lung cancer.
      Trials using erlotinib and pemetrexed showed improvement in overall survival.
      Consideration of trial design is critical for the interpretation of these
      results. Data on quality of life and cost have not been presented, but will
      ultimately be important in evaluating the usefulness of these approaches.

PMID- 20679541
TI  - Biomarkers with predictive and prognostic function in non-small cell lung cancer:
      ready for prime time?
AB  - Lung cancer is the leading cause of cancer-related mortality in the United
      States. Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all
      lung cancers. Most patients with NSCLC present with locoregionally advanced or
      metastatic disease, for which response rates and median overall survival remain
      poor. Platinum-based chemotherapy is the mainstay of treatment for NSCLC in both
      adjuvant and metastatic disease. Personalized chemotherapy and targeted biologic
      therapy based on a tumor's histologic and molecular profile have already shown
      promise in optimizing efficacy. Various markers are currently being investigated
      for their ability to guide treatment decision-making and management. This article
      describes these predictive and prognostic markers and details their current role,
      benefit, and potential future use in the management of patients with NSCLC.

PMID- 20679542
TI  - Health care for prisoners in Haiti.
AB  - Prisoners have disproportionate health care needs. Meeting those needs in a
      prison environment is challenging, especially in such resource-poor countries as
      Haiti. Even so, before the January 2010 earthquake, local and international
      organizations, in collaboration with the Haitian government, had been making
      significant progress to provide for the health needs of prisoners. The effort
      screened and identified prisoners for infectious disease, initiated appropriate
      care and treatment, and prepared prisoners for release to the community. Not only
      is it possible to establish an adequate prison health care program in a resource
      poor country, it is necessary. Without adequate management of prisoners' health
      needs, especially for such infectious diseases as HIV and tuberculosis, disease
      burden increases. Infectious disease can spread among prisoners and impact the
      public's health. Recovery for postearthquake Haiti, as any nation rebuilding
      following natural disaster or conflict, requires respect for rule of law. This
      includes humane detention and the delivery of justice and adequate health care
      for prisoners.

PMID- 20679543
TI  - Percutaneous heart valve replacement for aortic stenosis: state of the evidence.
AB  - Surgical aortic valve replacement (SAVR) is the only treatment known to improve
      symptoms and survival in patients with severe, symptomatic aortic stenosis.
      Perioperative mortality, however, is high among many patients for whom SAVR may
      be indicated. Percutaneous heart valve replacement (PHVR) is an emerging,
      catheter-based technology that allows for implantation of a prosthetic valve
      without open heart surgery. This review describes the available literature on
      PHVR for aortic stenosis, which comprised 84 published reports representing 76
      distinct studies and 2375 unique patients. Successful implantation was achieved
      in 94% of patients; 30-day survival was 89%. Differences between patients
      undergoing PHVR and those typically selected for SAVR make full interpretation of
      these results difficult. A large, multicenter, randomized, controlled trial
      comparing PHVR with SAVR or medical management was recently completed, with
      initial results expected in September 2010. Pending publication of findings from
      that trial, the available evidence is inadequate to determine the most
      appropriate clinical role of PHVR or the specific patient populations for whom it
      might eventually be indicated.

PMID- 20679544
TI  - Comparative effectiveness research: a progress report.
AB  - Sixteen months ago, comparative effectiveness research (CER) began its rapid
      rise, when the American Recovery and Reinvestment Act of 2009 allocated $1.1
      billion for CER. This progress report summarizes how the recipients of the funds
      the National Institutes of Health, Agency for Healthcare Research and Quality,
      and Office of the Secretary of the U.S. Department of Health and Human Services
      are spending the $1.1 billion, how the Institute of Medicine priority topics have
      fared in the agencies' funding programs, and the developing plans for a national
      CER program. As the United States works to absorb 32 million currently uninsured
      people into the health care system while simultaneously improving the quality of
      care and slowing cost increases, CER will increasingly be a necessary component
      of this change.

PMID- 20679545
TI  - Cardiac index as a correlate of brain volume: separating the wheat of normal
      aging from the chaff of vascular cognitive disorders.

PMID- 20679546
TI  - Cooling heads and hearts versus cooling our heels.

PMID- 20679547
TI  - Angiotensin-converting enzyme 2 suppresses pathological hypertrophy, myocardial
      fibrosis, and cardiac dysfunction.
AB  - BACKGROUND: Angiotensin-converting enzyme 2 (ACE2) is a pleiotropic
      monocarboxypeptidase capable of metabolizing several peptide substrates. We
      hypothesized that ACE2 is a negative regulator of angiotensin II (Ang II)
      mediated signaling and its adverse effects on the cardiovascular system. METHODS
      AND RESULTS: Ang II infusion (1.5 mg x kg(-1) x d(-1)) for 14 days resulted in
      worsening cardiac fibrosis and pathological hypertrophy in ACE2 knockout (Ace2(
      /y)) mice compared with wild-type (WT) mice. Daily treatment of Ang II-infused
      wild-type mice with recombinant human ACE2 (rhACE2; 2 mg x kg(-1) x d(-1) IP)
      blunted the hypertrophic response and expression of hypertrophy markers and
      reduced Ang II-induced superoxide production. Ang II-mediated myocardial fibrosis
      and expression of procollagen type I alpha 1, procollagen type III alpha 1,
      transforming growth factor-beta1, and fibronectin were also suppressed by rhACE2.
      Ang II-induced diastolic dysfunction was inhibited by rhACE2 in association with
      reduced plasma and myocardial Ang II and increased plasma Ang 1-7 levels. rhACE2
      treatment inhibited Ang II-mediated activation of protein kinase C-alpha and
      protein kinase C-beta1 protein levels and phosphorylation of the extracellular
      signal-regulated 1/2, Janus kinase 2, and signal transducer and activator of
      transcription 3 signaling pathways in wild-type mice. A subpressor dose of Ang II
      (0.15 mg . kg(-1) . d(-1)) resulted in a milder phenotype that was strikingly
      attenuated by rhACE2 (2 mg x kg(-1) x d(-1) IP). In adult ventricular
      cardiomyocytes and cardiofibroblasts, Ang II-mediated superoxide generation,
      collagen production, and extracellular signal-regulated 1/2 signaling were
      inhibited by rhACE2 in an Ang 1-7-dependent manner. Importantly, rhACE2 partially
      prevented the development of dilated cardiomyopathy in pressure-overloaded wild
      type mice. CONCLUSIONS: Elevated Ang II induced hypertension, myocardial
      hypertrophy, fibrosis, and diastolic dysfunction, which were exacerbated by ACE2
      deficiency, whereas rhACE2 attenuated Ang II- and pressure-overload-induced
      adverse myocardial remodeling. Hence, ACE2 is an important negative regulator of
      Ang II-induced heart disease and suppresses adverse myocardial remodeling.

PMID- 20679548
TI  - Intra-arrest transnasal evaporative cooling: a randomized, prehospital,
      multicenter study (PRINCE: Pre-ROSC IntraNasal Cooling Effectiveness).
AB  - BACKGROUND: Transnasal evaporative cooling has sufficient heat transfer capacity
      for effective intra-arrest cooling and improves survival in swine. The aim of
      this study was to determine the safety, feasibility, and cooling efficacy of
      prehospital transnasal cooling in humans and to explore its effects on
      neurologically intact survival to hospital discharge. METHODS AND RESULTS:
      Witnessed cardiac arrest patients with a treatment interval <or=20 minutes were
      randomized to intra-arrest cooling with a RhinoChill device (treatment group,
      n=96) versus standard care (control group, n=104). The final analysis included 93
      versus 101 patients, respectively. Both groups were cooled after hospital
      arrival. The patients had similar demographics, initial rhythms, rates of
      bystander cardiopulmonary resuscitation, and intervals to cardiopulmonary
      resuscitation and arrival of advanced life support personnel. Eighteen device
      related adverse events (1 periorbital emphysema, 3 epistaxis, 1 perioral bleed,
      and 13 nasal discolorations) were reported. Time to target temperature of 34
      degrees C was shorter in the treatment group for both tympanic (102 versus 282
      minutes, P=0.03) and core (155 versus 284 minutes, P=0.13) temperature. There
      were no significant differences in rates of return of spontaneous circulation
      between the groups (38% in treated subjects versus 43% in control subjects,
      P=0.48), in overall survival of those admitted alive (44% versus 31%,
      respectively, P=0.26), or in neurologically intact survival to discharge
      (Pittsburgh cerebral performance category scale 1 to 2, 34% versus 21%, P=0.21),
      although the study was not adequately powered to detect changes in these
      outcomes. CONCLUSIONS: Prehospital intra-arrest transnasal cooling is safe and
      feasible and is associated with a significant improvement in the time intervals
      required to cool patients.

PMID- 20679549
TI  - Prediction models for prolonged intensive care unit stay after cardiac surgery:
      systematic review and validation study.
AB  - BACKGROUND: Several models have been developed to predict prolonged stay in the
      intensive care unit (ICU) after cardiac surgery. However, no extensive
      quantitative validation of these models has yet been conducted. This study sought
      to identify and validate existing prediction models for prolonged ICU length of
      stay after cardiac surgery. METHODS AND RESULTS: After a systematic review of the
      literature, the identified models were applied on a large registry database
      comprising 11 395 cardiac surgical interventions. The probabilities of prolonged
      ICU length of stay based on the models were compared with the actual outcome to
      assess the discrimination and calibration performance of the models. Literature
      review identified 20 models, of which 14 could be included. Of the 6 models for
      the general cardiac surgery population, the Parsonnet model showed the best
      discrimination (area under the receiver operating characteristic curve=0.75 [95%
      confidence interval, 0.73 to 0.76]), followed by the European system for cardiac
      operative risk evaluation (EuroSCORE) (0.71 [0.70 to 0.72]) and a model by
      Huijskes and colleagues (0.71 [0.70 to 0.73]). Most of the models showed good
      calibration. CONCLUSIONS: In this validation of prediction models for prolonged
      ICU length of stay, 2 widely implemented models (Parsonnet, EuroSCORE), although
      originally designed for prediction of mortality, were superior in identifying
      patients with prolonged ICU length of stay.

PMID- 20679550
TI  - Exercise training stimulates ischemia-induced neovascularization via
      phosphatidylinositol 3-kinase/Akt-dependent hypoxia-induced factor-1 alpha
      reactivation in mice of advanced age.
AB  - BACKGROUND: Exercise stimulates the vascular response in pathological conditions,
      including ischemia; however, the molecular mechanisms by which exercise improves
      the impaired hypoxia-induced factor (HIF)-1 alpha-mediated response to hypoxia
      associated with aging are poorly understood. Here, we report that swimming
      training (ST) modulates the vascular response to ischemia in aged (24-month-old)
      mice. METHODS AND RESULTS: Aged wild-type mice (MMP-2(+/+)) that maintained ST
      (swimming 1 h/d) from day 1 after surgery were randomly assigned to 4 groups that
      were treated with either vehicle, LY294002, or deferoxamine for 14 days. Mice
      that were maintained in a sedentary condition served as controls. ST increased
      blood flow, capillary density, and levels of p-Akt, HIF-1 alpha, vascular
      endothelial growth factor, Fit-1, and matrix metalloproteinase-2 (MMP-2) in MMP
      2(+/+) mice. ST also increased the numbers of circulating endothelial progenitor
      cells and their function associated with activation of HIF-1 alpha. All of these
      effects were diminished by LY294002, an inhibitor of phosphatidylinositol 3
      kinase; enhanced by deferoxamine, an HIF-1 alpha stabilizer; and impaired by
      knockout of MMP-2. Finally, bone marrow transplantation confirmed that ST
      enhanced endothelial progenitor cell homing to ischemic sites in aged mice.
      CONCLUSIONS: ST can improve neovascularization in response to hypoxia via a
      phosphatidylinositol 3-kinase-dependent mechanism that is mediated by the HIF-1
      alpha/vascular endothelial growth factor/MMP-2 pathway in advanced age.

PMID- 20679551
TI  - Induction of therapeutic hypothermia by paramedics after resuscitation from out
      of-hospital ventricular fibrillation cardiac arrest: a randomized controlled
      trial.
AB  - BACKGROUND: Therapeutic hypothermia is recommended for the treatment of
      neurological injury after resuscitation from out-of-hospital cardiac arrest.
      Laboratory studies have suggested that earlier cooling may be associated with
      improved neurological outcomes. We hypothesized that induction of therapeutic
      hypothermia by paramedics before hospital arrival would improve outcome. METHODS
      AND RESULTS: In a prospective, randomized controlled trial, we assigned adults
      who had been resuscitated from out-of-hospital cardiac arrest with an initial
      cardiac rhythm of ventricular fibrillation to either prehospital cooling with a
      rapid infusion of 2 L of ice-cold lactated Ringer's solution or cooling after
      hospital admission. The primary outcome measure was functional status at hospital
      discharge, with a favorable outcome defined as discharge either to home or to a
      rehabilitation facility. A total of 234 patients were randomly assigned to either
      paramedic cooling (118 patients) or hospital cooling (116 patients). Patients
      allocated to paramedic cooling received a median of 1900 mL (first quartile 1000
      mL, third quartile 2000 mL) of ice-cold fluid. This resulted in a mean decrease
      in core temperature of 0.8 degrees C (P=0.01). In the paramedic-cooled group,
      47.5% patients had a favorable outcome at hospital discharge compared with 52.6%
      in the hospital-cooled group (risk ratio 0.90, 95% confidence interval 0.70 to
      1.17, P=0.43). CONCLUSIONS: In adults who have been resuscitated from out-of
      hospital cardiac arrest with an initial cardiac rhythm of ventricular
      fibrillation, paramedic cooling with a rapid infusion of large-volume, ice-cold
      intravenous fluid decreased core temperature at hospital arrival but was not
      shown to improve outcome at hospital discharge compared with cooling commenced in
      the hospital.

PMID- 20679553
TI  - Prevalence and clinical significance of aortic root dilation in highly trained
      competitive athletes.
AB  - BACKGROUND: Few data are available that address the impact of athletic training
      on aortic root size. We investigated the distribution, determinants, and clinical
      significance of aortic root dimension in a large population of highly trained
      athletes. METHODS AND RESULTS: Transverse aortic dimensions were assessed in 2317
      athletes (56% male), free of cardiovascular disease, aged 24.8+/-6.1 (range, 9 to
      59) years, engaged in 28 sports disciplines (28% participated in Olympic Games).
      In males, aortic root was 32.2+/-2.7 mm (range, 23 to 44; 99 th percentile=40
      mm); in females, aortic root was 27.5+/-2.6 mm (range, 20 to 36; 99 th
      percentile=34 mm). Aortic root was enlarged >or=40 mm in 17 male (1.3%) and
      >or=34 mm in 10 female (0.9%) subjects. Over an 8-year follow-up period, aortic
      dimension increased in these male athletes (40.9+/-1.3 to 42.9+/-3.6 mm; P<0.01)
      and dilated substantially (to 50, 50, and 48 mm) in 3, after 15 to 17 years of
      follow-up, in the absence of systemic disease. Aortic root did not increase
      significantly (34.9+/-0.9 to 35.4+/-2.1 mm; P=0.11) in female athletes. Multiple
      regression and covariance analysis showed that aortic dimension was largely
      explained by weight, height, left ventricular mass, and age (R(2)=0.63; P<0.001),
      with type of sports training having a significant but lower impact (P<0.003).
      CONCLUSIONS: An aortic root dimension >40 mm in highly conditioned male athletes
      (and >34 mm in female athletes) is uncommon, is unlikely to represent the
      physiological consequence of exercise training, and is most likely an expression
      of a pathological condition, mandating close clinical surveillance.

PMID- 20679554
TI  - Summaries for patients: Are abnormal lipid levels harmful in young adults?

PMID- 20679552
TI  - Cardiac index is associated with brain aging: the Framingham Heart Study.
AB  - BACKGROUND: Cardiac dysfunction is associated with neuroanatomic and
      neuropsychological changes in aging adults with prevalent cardiovascular disease,
      theoretically because systemic hypoperfusion disrupts cerebral perfusion,
      contributing to subclinical brain injury. We hypothesized that cardiac function,
      as measured by cardiac index, would be associated with preclinical brain magnetic
      resonance imaging (MRI) and neuropsychological markers of ischemia and Alzheimer
      disease in the community. METHODS AND RESULTS: Brain MRI, cardiac MRI,
      neuropsychological, and laboratory data were collected on 1504 Framingham
      Offspring Cohort participants free of clinical stroke, transient ischemic attack,
      or dementia (age, 61+/-9 years; 54% women). Neuropsychological and brain MRI
      variables were related to cardiac MRI-assessed cardiac index (cardiac output/body
      surface area). In multivariable-adjusted models, cardiac index was positively
      related to total brain volume (P=0.03) and information processing speed (P=0.02)
      and inversely related to lateral ventricular volume (P=0.048). When participants
      with clinically prevalent cardiovascular disease were excluded, the relation
      between cardiac index and total brain volume remained (P=0.02). Post hoc
      comparisons revealed that participants in the bottom cardiac index tertile
      (values <2.54) and middle cardiac index tertile (values between 2.54 and 2.92)
      had significantly lower brain volumes (P=0.04) than participants in the top
      cardiac index tertile (values >2.92). CONCLUSIONS: Although observational data
      cannot establish causality, our findings are consistent with the hypothesis that
      decreasing cardiac function, even at normal cardiac index levels, is associated
      with accelerated brain aging.

PMID- 20679555
TI  - Summaries for patients: Comparison of weight loss at 2 years on a low
      carbohydrate versus low-fat diet.

PMID- 20679556
TI  - Summaries for patients: What happens to people who need a breathing machine for
      more than a few days?

PMID- 20679557
TI  - In the clinic. Dyslipidemia.
AB  - This issue provides a clinical overview of dyslipidemia focusing on prevention,
      diagnosis, treatment, practice improvement, and patient information. Readers can
      complete the accompanying CME quiz for 1.5 credits. Only ACP members and
      individual subscribers can access the electronic features of In the Clinic. Non
      subscribers who wish to access this issue of In the Clinic can elect "Pay for
      View." Subscribers can receive 1.5 category 1 CME credits by completing the CME
      quiz that accompanies this issue of In the Clinic. The content of In the Clinic
      is drawn from the clinical information and education resources of the American
      College of Physicians (ACP), including PIER (Physicians' Information and
      Education Resource) and MKSAP (Medical Knowledge and Self Assessment Program).
      Annals of Internal Medicine editors develop In the Clinic from these primary
      sources in collaboration with the ACP's Medical Education and Publishing division
      and with assistance of science writers and physician writers. Editorial
      consultants from PIER and MKSAP provide expert review of the content. Readers who
      are interested in these primary resources for more detail can consult
      www.acponline.org, http://pier.acponline.org, and other resources referenced
      within each issue of In the Clinic.

PMID- 20679558
TI  - Nonoptimal lipids commonly present in young adults and coronary calcium later in
      life: the CARDIA (Coronary Artery Risk Development in Young Adults) study.
AB  - BACKGROUND: Dyslipidemia causes coronary heart disease in middle-aged and elderly
      adults, but the consequences of lipid exposure during young adulthood are
      unclear. OBJECTIVE: To assess whether nonoptimal lipid levels during young
      adulthood cause atherosclerotic changes that persist into middle age. DESIGN:
      Prospective cohort study. SETTING: 4 cities in the United States. PARTICIPANTS:
      3258 participants from the 5115 black and white men and women recruited at age 18
      to 30 years in 1985 to 1986 for the CARDIA (Coronary Artery Risk Development in
      Young Adults) study. MEASUREMENTS: Low-density lipoprotein (LDL) and high-density
      lipoprotein (HDL) cholesterol, triglycerides, and coronary calcium. Time-averaged
      cumulative exposures to lipids between age 20 and 35 years were estimated by
      using repeated serum lipid measurements over 20 years in the CARDIA study; these
      measurements were then related to coronary calcium scores assessed later in life
      (45 years [SD, 4]). RESULTS: 2824 participants (87%) had nonoptimal levels of LDL
      cholesterol (>or=2.59 mmol/L [>or=100 mg/dL]), HDL cholesterol (<1.55 mmol/L [<60
      mg/dL]), or triglycerides (>or=1.70 mmol/L [>or=150 mg/dL]) during young
      adulthood. Coronary calcium prevalence 2 decades later was 8% in participants who
      maintained optimal LDL levels (<1.81 mmol/L [<70 mg/dL]), and 44% in participants
      with LDL cholesterol levels of 4.14 mmol/L (160 mg/dL) or greater (P < 0.001).
      The association was similar across race and sex and strongly graded, with odds
      ratios for coronary calcium of 1.5 (95% CI, 0.7 to 3.3) for LDL cholesterol
      levels of 1.81 to 2.56 mmol/L (70 to 99 mg/dL), 2.4 (CI, 1.1 to 5.3) for levels
      of 2.59 to 3.34 mmol/L (100 to 129 mg/dL), 3.3 (CI, 1.3 to 7.8) for levels of
      3.37 to 4.12 mmol/L (130 to 159 mg/dL), and 5.6 (CI, 2.0 to 16) for levels of
      4.14 mmol/L (160 mg/dL) or greater, compared with levels less than 1.81 mmol/L
      (<70 mg/dL), after adjustment for lipid exposure after age 35 years and other
      coronary risk factors. Both LDL and HDL cholesterol levels were independently
      associated with coronary calcium after participants who were receiving lipid
      lowering medications or had clinically abnormal lipid levels were excluded.
      LIMITATION: Coronary calcium, although a strong predictor of future coronary
      heart disease, is not a clinical outcome. CONCLUSION: Nonoptimal levels of LDL
      and HDL cholesterol during young adulthood are independently associated with
      coronary atherosclerosis 2 decades later. PRIMARY FUNDING SOURCE: National Heart,
      Lung, and Blood Institute.

PMID- 20679559
TI  - Weight and metabolic outcomes after 2 years on a low-carbohydrate versus low-fat
      diet: a randomized trial.
AB  - BACKGROUND: Previous studies comparing low-carbohydrate and low-fat diets have
      not included a comprehensive behavioral treatment, resulting in suboptimal weight
      loss. OBJECTIVE: To evaluate the effects of 2-year treatment with a low
      carbohydrate or low-fat diet, each of which was combined with a comprehensive
      lifestyle modification program. DESIGN: Randomized parallel-group trial.
      (ClinicalTrials.gov registration number: NCT00143936) SETTING: 3 academic medical
      centers. PATIENTS: 307 participants with a mean age of 45.5 years (SD, 9.7 years)
      and mean body mass index of 36.1 kg/m(2) (SD, 3.5 kg/m(2)). INTERVENTION: A low
      carbohydrate diet, which consisted of limited carbohydrate intake (20 g/d for 3
      months) in the form of low-glycemic index vegetables with unrestricted
      consumption of fat and protein. After 3 months, participants in the low
      carbohydrate diet group increased their carbohydrate intake (5 g/d per wk) until
      a stable and desired weight was achieved. A low-fat diet consisted of limited
      energy intake (1200 to 1800 kcal/d; <or=30% calories from fat). Both diets were
      combined with comprehensive behavioral treatment. MEASUREMENTS: Weight at 2 years
      was the primary outcome. Secondary measures included weight at 3, 6, and 12
      months and serum lipid concentrations, blood pressure, urinary ketones, symptoms,
      bone mineral density, and body composition throughout the study. RESULTS: Weight
      loss was approximately 11 kg (11%) at 1 year and 7 kg (7%) at 2 years. There were
      no differences in weight, body composition, or bone mineral density between the
      groups at any time point. During the first 6 months, the low-carbohydrate diet
      group had greater reductions in diastolic blood pressure, triglyceride levels,
      and very-low-density lipoprotein cholesterol levels, lesser reductions in low
      density lipoprotein cholesterol levels, and more adverse symptoms than did the
      low-fat diet group. The low-carbohydrate diet group had greater increases in high
      density lipoprotein cholesterol levels at all time points, approximating a 23%
      increase at 2 years. LIMITATION: Intensive behavioral treatment was provided,
      patients with dyslipidemia and diabetes were excluded, and attrition at 2 years
      was high. CONCLUSION: Successful weight loss can be achieved with either a low
      fat or low-carbohydrate diet when coupled with behavioral treatment. A low
      carbohydrate diet is associated with favorable changes in cardiovascular disease
      risk factors at 2 years. PRIMARY FUNDING SOURCE: National Institutes of Health.

PMID- 20679560
TI  - Outcome reporting among drug trials registered in ClinicalTrials.gov.
AB  - BACKGROUND: Clinical trial registries are in widespread use to promote
      transparency around trials and their results. OBJECTIVE: To describe
      characteristics of drug trials listed in ClinicalTrials.gov and examine whether
      the funding source of these trials is associated with favorable published
      outcomes. DESIGN: An observational study of safety and efficacy trials for
      anticholesteremics, antidepressants, antipsychotics, proton-pump inhibitors, and
      vasodilators conducted between 2000 and 2006. SETTING: ClinicalTrials.gov, a Web
      based registry of clinical trials launched in 1999. MEASUREMENTS: Publications
      resulting from the trials for the 5 drug categories of interest were identified,
      and data were abstracted on the trial record and publication, including timing of
      registration, elements of the study design, funding source, publication date, and
      study outcomes. Assessments were based on the primary funding categories of
      industry, government agencies, and nonprofit or nonfederal organizations.
      RESULTS: Among 546 drug trials, 346 (63%) were primarily funded by industry, 74
      (14%) by government sources, and 126 (23%) by nonprofit or nonfederal
      organizations. Trials funded by industry were more likely to be phase 3 or 4
      trials (88.7%; P < 0.001 across groups), to use an active comparator in
      controlled trials (36.8%; P = 0.010 across groups), to be multicenter (89.0%; P <
      0.001 across groups), and to enroll more participants (median sample size, 306
      participants; P < 0.001 across groups). Overall, 362 (66.3%) trials had published
      results. Industry-funded trials reported positive outcomes in 85.4% of
      publications, compared with 50.0% for government-funded trials and 71.9% for
      nonprofit or nonfederal organization-funded trials (P < 0.001). Trials funded by
      nonprofit or nonfederal sources with industry contributions were also more likely
      to report positive outcomes than those without industry funding (85.0% vs. 61.2%;
      P = 0.013). Rates of trial publication within 24 months of study completion
      ranged from 32.4% among industry-funded trials to 56.2% among nonprofit or
      nonfederal organization-funded trials without industry contributions (P = 0.005
      across groups). LIMITATIONS: The publication status of a trial could not always
      be confirmed, which could result in misclassification. Additional information on
      study protocols and comprehensive trial results were not available to further
      explore underlying factors for the association between funding source and outcome
      reporting. CONCLUSION: In this sample of registered drug trials, those funded by
      industry were less likely to be published within 2 years of study completion and
      were more likely to report positive outcomes than were trials funded by other
      sources. PRIMARY FUNDING SOURCE: National Library of Medicine and National
      Institute of Child Health and Human Development, National Institutes of Health.

PMID- 20679562
TI  - The development of clinical practice guidelines and guidance statements of the
      American College of Physicians: summary of methods.
AB  - The American College of Physicians (ACP) established its evidence-based clinical
      practice guidelines program in 1981. The ACP's Guidelines Committee and the staff
      of the Clinical Programs and Quality of Care Department develop the clinical
      recommendations. The ACP develops 2 different types of clinical recommendations:
      clinical practice guidelines and clinical guidance statements. The ACP clinical
      practice guidelines and guidance statements follow a multistep development
      process that includes a systematic review of the evidence, deliberation of the
      evidence by the committee, summary recommendations, and evidence and
      recommendation grading. All ACP clinical practice guidelines and clinical
      guidance statements, if not updated, are considered automatically withdrawn or
      invalid 5 years after publication or once an update has been issued.

PMID- 20679561
TI  - One-year trajectories of care and resource utilization for recipients of
      prolonged mechanical ventilation: a cohort study.
AB  - BACKGROUND: Growing numbers of critically ill patients receive prolonged
      mechanical ventilation. Little is known about the patterns of care as patients
      transition from acute care hospitals to postacute care facilities or about the
      associated resource utilization. OBJECTIVE: To describe 1-year trajectories of
      care and resource utilization for patients receiving prolonged mechanical
      ventilation. DESIGN: 1-year prospective cohort study. SETTING: 5 intensive care
      units at Duke University Medical Center, Durham, North Carolina. PARTICIPANTS:
      126 patients receiving prolonged mechanical ventilation (defined as ventilation
      for >or=4 days with tracheostomy placement or ventilation for >or=21 days without
      tracheostomy), as well as their 126 surrogates and 54 intensive care unit
      physicians, enrolled consecutively over 1 year. MEASUREMENTS: Patients and
      surrogates were interviewed in the hospital, as well as 3 and 12 months after
      discharge, to determine patient survival, functional status, and facility type
      and duration of postdischarge care. Physicians were interviewed in the hospital
      to elicit prognoses. Institutional billing records were used to assign costs for
      acute care, outpatient care, and interfacility transportation. Medicare claims
      data were used to assign costs for postacute care. RESULTS: 103 (82%) hospital
      survivors had 457 separate transitions in postdischarge care location (median, 4
      transitions [interquartile range, 3 to 5 transitions]), including 68 patients
      (67%) who were readmitted at least once. Patients spent an average of 74% (95%
      CI, 68% to 80%) of all days alive in a hospital or postacute care facility or
      receiving home health care. At 1 year, 11 patients (9%) had a good outcome (alive
      with no functional dependency), 33 (26%) had a fair outcome (alive with moderate
      dependency), and 82 (65%) had a poor outcome (either alive with complete
      functional dependency [4 patients; 21%] or dead [56 patients; 44%]). Patients
      with poor outcomes were older, had more comorbid conditions, and were more
      frequently discharged to a postacute care facility than patients with either fair
      or good outcomes (P < 0.05 for all). The mean cost per patient was $306,135 (SD,
      $285,467), and total cohort cost was $38.1 million, for an estimated $3.5 million
      per independently functioning survivor at 1 year. LIMITATION: The results of this
      single-center study may not be applicable to other centers. CONCLUSION: Patients
      receiving prolonged mechanical ventilation have multiple transitions of care,
      resulting in substantial health care costs and persistent, profound disability.
      The optimism of surrogate decision makers should be balanced by discussions of
      these outcomes when considering a course of prolonged life support. PRIMARY
      FUNDING SOURCE: None.

PMID- 20679563
TI  - On humility.
AB  - The new professionalism movement in medical education takes seriously the old
      medical virtues. Perhaps the most difficult virtue to understand and practice is
      humility, which seems out of place in a medical culture characterized by
      arrogance, assertiveness, and a sense of entitlement. Countercultural though it
      is, humility need not suggest weakness or lack of self-confidence. On the
      contrary, humility requires toughness and emotional resilience. Humility in
      medicine manifests itself as unflinching self-awareness; empathic openness to
      others; and a keen appreciation of, and gratitude for, the privilege of caring
      for sick persons. Justified pride in medicine's accomplishments should neither
      rule out nor diminish our humility as healers.

PMID- 20679564
TI  - Cardiovascular risk in young persons: secondary or primordial prevention?

PMID- 20679565
TI  - Survivorship will be the defining challenge of critical care in the 21st century.

PMID- 20679566
TI  - The scent of cancer.
AB  - If forced to choose, I would give up the sense of smell first. It is both the
      hardest sense to take for granted and the easiest to imagine the possibility of
      living without. Yet, being able to smell adds a vividness and fragrant richness
      to life-and if we pay careful attention to our noses in the clinic, they can tell
      us tales worth knowing.

PMID- 20679567
TI  - Does inconclusive evidence for vitamin D supplementation to reduce risk for
      cardiovascular disease warrant pessimism?

PMID- 20679568
TI  - Does inconclusive evidence for vitamin D supplementation to reduce risk for
      cardiovascular disease warrant pessimism?

PMID- 20679570
TI  - Does inconclusive evidence for vitamin D supplementation to reduce risk for
      cardiovascular disease warrant pessimism?

PMID- 20679571
TI  - Herpes zoster vaccine in nursing facility residents: safety questions remain.

PMID- 20679573
TI  - Misleading statement in trial on false-positive results in lung cancer screening.

PMID- 20679576
TI  - Images in cardiovascular medicine: Detection of giant cell aortitis using 18F
      fluorodeoxyglucose positron emission tomography computed tomography.

PMID- 20679577
TI  - Images in cardiovascular medicine: Emphysematous aortitis.

PMID- 20679578
TI  - Letter by Potter and Le Lorier regarding article, "Cardiovascular outcomes and
      mortality in patients using clopidogrel with proton pump inhibitors after
      percutaneous coronary intervention or acute coronary syndrome".

PMID- 20679579
TI  - Letter by Di Marco and Brand regarding article, "Reduction of circulating soluble
      fms-like tyrosine kinase-1 plays a significant role in renal dysfunction
      associated aggravation of atherosclerosis".

PMID- 20679582
TI  - Dilated cardiomyopathy with conduction disease and arrhythmia.

PMID- 20679581
TI  - Stem cell therapy for vascular regeneration: adult, embryonic, and induced
      pluripotent stem cells.

PMID- 20679583
TI  - Images in cardiovascular medicine: Imaging of cardiac sarcoid lesions using
      fasting cardiac 18F-fluorodeoxyglucose positron emission tomography: an autopsy
      case.

PMID- 20679584
TI  - Galileo Galilei: scientist and artist.

PMID- 20679585
TI  - Impaired visual object processing across an occipital-frontal-hippocampal brain
      network in schizophrenia: an integrated neuroimaging study.
AB  - CONTEXT: Perceptual closure is the ability to identify objects based on partial
      information and depends on the function of a distributed network of brain regions
      that include the dorsal and the ventral visual streams, prefrontal cortex (PFC),
      and hippocampus. OBJECTIVE: To evaluate network-level interactions during
      perceptual closure in schizophrenia using parallel event-related potential (ERP),
      functional magnetic resonance imaging (fMRI), and neuropsychological assessment.
      DESIGN: Case-control study. SETTING: Inpatient and outpatient facilities
      associated with the Nathan Kline Institute for Psychiatric Research. Patients
      Twenty-seven patients with schizophrenia or schizoaffective disorder and 23
      healthy controls. Intervention Event-related potentials were obtained from 24
      patients and 20 healthy volunteers in response to fragmented (closeable) and
      control-scrambled (noncloseable) line drawings. Functional MRI was performed in
      11 patients and 12 controls. Main Outcome Measure Patterns of between-group
      differences for predefined ERP components and fMRI regions of interest were
      determined using both analysis of variance and structural equation modeling.
      Global neuropsychological performance was assessed using standard
      neuropsychological batteries. RESULTS: Patients showed impaired generation of
      event-related components reflecting early sensory and later closure-related
      activity. In fMRI, patients showed impaired activation of the dorsal and ventral
      visual regions, PFC, and hippocampus. Impaired activation of dorsal stream visual
      regions contributed significantly to impaired PFC activation, which contributed
      significantly to impaired activation of the hippocampus and ventral visual
      stream. Impaired ventral stream and hippocampal activation contributed
      significantly to deficits on neuropsychological measures of perceptual
      organization. CONCLUSIONS: Schizophrenia is associated with severe activation
      deficits across a distributed network of sensory and higher order cognitive
      regions. Deficit in early visual processing within the dorsal visual stream
      contributes significantly to impaired frontal activation, which, in turn, leads
      to dysregulation of the hippocampus and ventral visual stream. Dysfunction within
      this network underlies deficits in more traditional neurocognitive measures,
      supporting distributed models of brain dysfunction in schizophrenia.

PMID- 20679586
TI  - Short-term effects of antipsychotic treatment on cerebral function in drug-naive
      first-episode schizophrenia revealed by "resting state" functional magnetic
      resonance imaging.
AB  - CONTEXT: Most of what we know about antipsychotic drug effects is at the receptor
      level, distal from the neural system effects that mediate their clinical
      efficacy. Studying cerebral function in antipsychotic-naive patients with
      schizophrenia before and after pharmacotherapy can enhance understanding of the
      therapeutic mechanisms of these clinically effective treatments. OBJECTIVE: To
      examine alterations of regional and neural network function in antipsychotic
      naive patients with first-episode schizophrenia before and after treatment with
      second-generation antipsychotic medication. DESIGN: Case-control study. SETTING:
      Huaxi MR Research Center and Mental Health Centre of the West China Hospital.
      PARTICIPANTS: Thirty-four antipsychotic-naive patients with first-episode
      schizophrenia were scanned using gradient-echo echo-planar imaging while in a
      resting state. After 6 weeks of antipsychotic treatment, patients were rescanned.
      Thirty-four matched healthy control subjects were studied at baseline for
      comparison purposes. MAIN OUTCOME MEASURES: The amplitude of low-frequency
      fluctuations (ALFF) of blood oxygen level-dependent signals, believed to reflect
      spontaneous neural activity, was used to characterize regional cerebral function.
      Functional connectivity across brain regions was evaluated using a seed voxel
      correlation approach and an independent component analysis. Changes in these
      measures after treatment were examined to characterize effects of antipsychotic
      drugs on regional function and functional integration. RESULTS: After short-term
      treatment with second-generation antipsychotic medications, patients showed
      increased ALFF, particularly in the bilateral prefrontal and parietal cortex,
      left superior temporal cortex, and right caudate nucleus. Increased regional ALFF
      was associated with a reduction of clinical symptoms, and a widespread
      attenuation in functional connectivity was observed that was correlated with
      increased regional ALFF. CONCLUSIONS: We demonstrate for the first time, to our
      knowledge, that widespread increased regional synchronous neural activity occurs
      after antipsychotic therapy, accompanied by decreased integration of function
      across widely distributed neural networks. These findings contribute to the
      understanding of the complex systems-level effects of antipsychotic drugs.

PMID- 20679587
TI  - A randomized add-on trial of an N-methyl-D-aspartate antagonist in treatment
      resistant bipolar depression.
AB  - CONTEXT: Existing therapies for bipolar depression have a considerable lag of
      onset of action. Pharmacological strategies that produce rapid antidepressant
      effects-for instance, within a few hours or days-would have an enormous impact on
      patient care and public health. OBJECTIVE: To determine whether an N-methyl-D
      aspartate-receptor antagonist produces rapid antidepressant effects in subjects
      with bipolar depression. DESIGN: A randomized, placebo-controlled, double-blind,
      crossover, add-on study conducted from October 2006 to June 2009. SETTING: Mood
      Disorders Research Unit at the National Institute of Mental Health, Bethesda,
      Maryland. Patients Eighteen subjects with DSM-IV bipolar depression (treatment
      resistant). INTERVENTIONS: Subjects maintained at therapeutic levels of lithium
      or valproate received an intravenous infusion of either ketamine hydrochloride
      (0.5 mg/kg) or placebo on 2 test days 2 weeks apart. The Montgomery-Asberg
      Depression Rating Scale was used to rate subjects at baseline and at 40, 80, 110,
      and 230 minutes and on days 1, 2, 3, 7, 10, and 14 postinfusion. MAIN OUTCOME
      MEASURES: Change in Montgomery-Asberg Depression Rating Scale primary efficacy
      measure scores. RESULTS: Within 40 minutes, depressive symptoms significantly
      improved in subjects receiving ketamine compared with placebo (d = 0.52, 95%
      confidence interval [CI], 0.28-0.76); this improvement remained significant
      through day 3. The drug difference effect size was largest at day 2 (d = 0.80,
      95% CI, 0.55-1.04). Seventy-one percent of subjects responded to ketamine and 6%
      responded to placebo at some point during the trial. One subject receiving
      ketamine and 1 receiving placebo developed manic symptoms. Ketamine was generally
      well tolerated; the most common adverse effect was dissociative symptoms, only at
      the 40-minute point. CONCLUSION: In patients with treatment-resistant bipolar
      depression, robust and rapid antidepressant effects resulted from a single
      intravenous dose of an N-methyl-D-aspartate antagonist.

PMID- 20679588
TI  - Brain function in carriers of a genome-wide supported bipolar disorder variant.
AB  - CONTEXT: The neural abnormalities underlying genetic risk for bipolar disorder, a
      severe, common, and highly heritable psychiatric condition, are largely unknown.
      An opportunity to define these mechanisms is provided by the recent discovery,
      through genome-wide association, of a single-nucleotide polymorphism (rs1006737)
      strongly associated with bipolar disorder within the CACNA1C gene, encoding the
      alpha subunit of the L-type voltage-dependent calcium channel Ca(v)1.2.
      OBJECTIVE: To determine whether the genetic risk associated with rs1006737 is
      mediated through hippocampal function. DESIGN: Functional magnetic resonance
      imaging study. SETTING: University hospital. PARTICIPANTS: A total of 110 healthy
      volunteers of both sexes and of German descent in the Hardy-Weinberg equilibrium
      for rs1006737. MAIN OUTCOME MEASURES: Blood oxygen level-dependent signal during
      an episodic memory task and behavioral and psychopathological measures. RESULTS:
      Using an intermediate phenotype approach, we show that healthy carriers of the
      CACNA1C risk variant exhibit a pronounced reduction of bilateral hippocampal
      activation during episodic memory recall and diminished functional coupling
      between left and right hippocampal regions. Furthermore, risk allele carriers
      exhibit activation deficits of the subgenual anterior cingulate cortex, a region
      repeatedly associated with affective disorders and the mediation of adaptive
      stress-related responses. The relevance of these findings for affective disorders
      is supported by significantly higher psychopathology scores for depression,
      anxiety, obsessive-compulsive thoughts, interpersonal sensitivity, and
      neuroticism in risk allele carriers, correlating negatively with the observed
      regional brain activation. CONCLUSIONS: Our data demonstrate that rs1006737 or
      genetic variants in linkage disequilibrium with it are functional in the human
      brain and provide a neurogenetic risk mechanism for bipolar disorder backed by
      genome-wide evidence.

PMID- 20679589
TI  - Cost-effectiveness analysis of a rural telemedicine collaborative care
      intervention for depression.
AB  - CONTEXT: Collaborative care interventions for depression in primary care settings
      are clinically beneficial and cost-effective. Most prior studies were conducted
      in urban settings. OBJECTIVE: To examine the cost-effectiveness of a rural
      telemedicine-based collaborative care depression intervention. DESIGN: Randomized
      controlled trial of intervention vs usual care. SETTING: Seven small (serving
      1000 to 5000 veterans) Veterans Health Administration community-based outpatient
      clinics serving rural catchment areas in 3 mid-South states. Each site had
      interactive televideo dedicated to mental health but no psychiatrist or
      psychologist on site. Patients Among 18 306 primary care patients who were
      screened, 1260 (6.9%) screened positive for depression; 395 met eligibility
      criteria and were enrolled from April 2003 to September 2004. Of those enrolled,
      360 (91.1%) completed a 6-month follow-up and 335 (84.8%) completed a 12-month
      follow-up. Intervention A stepped-care model for depression treatment was used by
      an off-site depression care team to make treatment recommendations via electronic
      medical record. The team included a nurse depression care manager, clinical
      pharmacist, and psychiatrist. The depression care manager communicated with
      patients via telephone and was supported by computerized decision support
      software. MAIN OUTCOME MEASURES: The base case cost analysis included outpatient,
      pharmacy, and intervention expenditures. The effectiveness outcomes were
      depression-free days and quality-adjusted life years (QALYs) calculated using the
      12-Item Short Form Health Survey standard gamble conversion formula. RESULTS: The
      incremental depression-free days outcome was not significant (P = .10);
      therefore, further cost-effectiveness analyses were not done. The incremental
      QALY outcome was significant (P = .04) and the mean base case incremental cost
      effectiveness ratio was $85 634/QALY. Results adding inpatient costs were $111
      999/QALY to $132 175/QALY. CONCLUSIONS: In rural settings, a telemedicine-based
      collaborative care intervention for depression is effective and expensive. The
      mean base case result was $85 634/QALY, which is greater than cost per QALY
      ratios reported for other, mostly urban, depression collaborative care
      interventions.

PMID- 20679590
TI  - Full spectrum of psychiatric outcomes among offspring with parental history of
      mental disorder.
AB  - CONTEXT: While concordant parent/offspring risks for specific mental disorders
      are well established, knowledge of the broader range of psychiatric outcomes
      among offspring with parental history of mental disorder is lacking. OBJECTIVE:
      To examine the full range of mental health outcomes among offspring of parents
      with serious and other mental disorders compared with those whose parents had no
      such history. DESIGN: Population-based cohort study. Offspring were followed up
      from their 14th birthday for the development of mental disorders based on both
      outpatient and inpatient hospital data. SETTING: Danish population. PARTICIPANTS:
      All offspring born in Denmark between 1980 and 1994 (N = 865 078) with follow-up
      to December 2008. MAIN OUTCOME MEASURES: Incidence rates, incidence rate ratios,
      and cumulative incidences for offspring psychiatric outcomes. RESULTS: Parental
      serious mental disorder (SMD) (nonaffective or affective psychosis) was found to
      be positively associated with virtually all offspring psychiatric outcomes,
      including those not hitherto regarded as clinically related. Offspring of parents
      without SMD but with a history of "other mental disorder" were also found to be
      at increased risk of developing a range of mental disorders. The strongest
      associations were found where both parents had a history of mental disorder (eg,
      offspring of 2 parents with SMD were 13 times more likely to develop
      schizophrenia). Elevated risks were not confined to concordant parent/offspring
      disorders (eg, offspring of 2 parents with SMD were 8 times more likely to
      develop substance misuse disorders). CONCLUSIONS: The impact of parental history
      of mental disorder was not confined to elevated offspring risk of concordant
      disorders but rather offspring are at increased risk of a wide range of mental
      disorders, particularly those with 2 affected parents. Our results imply an
      important role for etiological factors giving rise to broad, as well as specific,
      familial vulnerabilities. These findings also have potential implications for
      diagnostic classification.

PMID- 20679592
TI  - Prenatal smoking exposure and the risk of psychiatric morbidity into young
      adulthood.
AB  - CONTEXT: Prenatal smoking exposure modulates brain development, which may deviate
      mental development of the offspring. OBJECTIVE: To study the effects of prenatal
      smoking exposure on psychiatric morbidity and mortality among Finnish young
      adults by means of population-based longitudinal register data. DESIGN:
      Information on maternal smoking as reported by the mothers (0, <10, or >10
      cigarettes a day) and other background factors (maternal age and parity and
      child's sex, gestational age, birth weight, and 5-minute Apgar score) was derived
      from the Finnish Medical Birth Register. Information on children's psychiatric
      diagnoses related to outpatient visits (1998-2007), children's inpatient care
      (1987-2007), and mothers' psychiatric inpatient care (1969-1989) was derived from
      the Finnish Hospital Discharge Register. Information on deaths and their causes
      for the children (1987-2007) was received from the Cause-of-Death Register.
      SETTING: Population-based study of all singletons born in Finland from 1987 to
      1989 with information on prenatal smoking exposure. Patients The source
      population included all singleton births in Finland from January 1, 1987, through
      December 31, 1989 (n = 175 869), excluding children with major congenital
      anomalies (3.1%) and children who died during the first week of life (0.3%). MAIN
      OUTCOME MEASURES: Psychiatric morbidity and mortality. RESULTS: The prevalence of
      maternal smoking was 15.3%. The risk of psychiatric morbidity was significantly
      higher in the exposed children than in the unexposed children. Among the
      offspring of mothers who smoked fewer than 10 cigarettes a day, 21.0% had any
      psychiatric diagnoses (adjusted odds ratio [OR], 1.53 [95% confidence interval
      (CI), 1.47-1.60]) compared with 24.7% among those of mothers who smoked more than
      10 cigarettes a day (1.85 [1.74-1.96]) and 13.7% in the unexposed children (the
      reference group). The risk was significantly increased for most of the
      psychiatric diagnoses. The strongest effects were in psychiatric disorders due to
      psychoactive substance use and in behavioral and emotional disorders. The risk of
      mortality was significantly higher in children exposed to more than 10 cigarettes
      a day (OR, 1.69 [95% CI, 1.31-2.19]) compared with unexposed children.
      CONCLUSION: Prenatal smoking exposure is associated with an increased risk of
      psychiatric morbidity, whereas prenatal exposure to more than 10 cigarettes a day
      increases the risk of mortality in childhood, adolescence, and young adulthood.

PMID- 20679591
TI  - Neurobehavioral abnormalities in first-degree relatives of individuals with
      autism.
AB  - CONTEXT: Studying sensorimotor and neurocognitive impairments in unaffected
      family members of individuals with autism may help identify familial
      pathophysiological mechanisms associated with the disorder. OBJECTIVE: To
      determine whether atypical sensorimotor or neurocognitive characteristics
      associated with autism are present in first-degree relatives of individuals with
      autism. DESIGN: Case-control comparison of neurobehavioral functions. SETTING:
      University medical center. PARTICIPANTS: Fifty-seven first-degree relatives of
      individuals with autism and 40 age-, sex-, and IQ-matched healthy control
      participants (aged 8-54 years). MAIN OUTCOME MEASURES: Oculomotor tests of
      sensorimotor responses (saccades and smooth pursuit); procedural learning and
      response inhibition; neuropsychological tests of motor, memory, and executive
      functions; and psychological measures of social behavior, communication skills,
      and obsessive-compulsive behaviors. RESULTS: On eye movement testing, family
      members demonstrated saccadic hypometria, reduced steady-state pursuit gain, and
      a higher rate of voluntary response inhibition errors relative to controls. They
      also showed lateralized deficits in procedural learning and open-loop pursuit
      gain (initial 100 milliseconds of pursuit) and increased variability in the
      accuracy of large-amplitude saccades that were confined to rightward movements.
      In neuropsychological studies, only executive functions were impaired relative to
      those of controls. Family members reported more communication abnormalities and
      obsessive-compulsive behaviors than controls. Deficits across oculomotor,
      neuropsychological, and psychological domains were relatively independent from
      one another. CONCLUSIONS: Family members of individuals with autism demonstrate
      oculomotor abnormalities implicating pontocerebellar and frontostriatal circuits
      and left-lateralized alterations of frontotemporal circuitry and striatum. The
      left-lateralized alterations have not been identified in other neuropsychiatric
      disorders and are of interest given atypical brain lateralization and language
      development associated with the disorder. Similar oculomotor deficits have been
      reported in individuals with autism, suggesting that they may be familial and
      useful for studies of neurophysiological and genetic mechanisms in autism.

PMID- 20679593
TI  - Effects of expectation on placebo-induced dopamine release in Parkinson disease.
AB  - CONTEXT: Expectations play a central role in the mechanism of the placebo effect.
      In Parkinson disease (PD), the placebo effect is associated with release of
      endogenous dopamine in both nigrostriatal and mesoaccumbens projections, yet the
      factors that control this dopamine release are undetermined. OBJECTIVE: To
      determine how the strength of expectation of clinical improvement influences the
      degree of striatal dopamine release in response to placebo in patients with
      moderate PD. DESIGN: Randomized, repeated-measures study with perceived
      expectation as the independent between-subjects variable. SETTING: University of
      British Columbia Hospital, Vancouver, British Columbia, Canada. Patients Thirty
      five patients with mild to moderate PD undergoing levodopa treatment.
      Intervention Verbal manipulation was used to modulate the expectations of
      patients, who were told that they had a particular probability (25%, 50%, 75%, or
      100%) of receiving active medication when they in fact received placebo. MAIN
      OUTCOME MEASURES: The dopaminergic response to placebo was measured using
      [11C]raclopride positron emission tomography. The clinical response was also
      measured (Unified Parkinson Disease Rating Scale) and subjective responses were
      ascertained using patient self-report. RESULTS: Significant dopamine release
      occurred when the declared probability of receiving active medication was 75%,
      but not at other probabilities. Placebo-induced dopamine release in all regions
      of the striatum was also highly correlated with the dopaminergic response to open
      administration of active medication. Whereas response to prior medication was the
      major determinant of placebo-induced dopamine release in the motor striatum,
      expectation of clinical improvement was additionally required to drive dopamine
      release in the ventral striatum. CONCLUSIONS: The strength of belief of
      improvement can directly modulate dopamine release in patients with PD. Our
      findings demonstrate the importance of uncertainty and/or salience over and above
      a patient's prior treatment response in regulating the placebo effect and have
      important implications for the interpretation and design of clinical trials.

PMID- 20679595
TI  - Metastatic mucinous tubular and spindle cell carcinoma of the kidney responding
      to sunitinib.

PMID- 20679594
TI  - Lung cancer cell lines as tools for biomedical discovery and research.
AB  - Lung cancer cell lines have made a substantial contribution to lung cancer
      translational research and biomedical discovery. A systematic approach to
      initiating and characterizing cell lines from small cell and non-small cell lung
      carcinomas has led to the current collection of more than 200 lung cancer cell
      lines, a number that exceeds those for other common epithelial cancers combined.
      The ready availability and widespread dissemination of the lines to investigators
      worldwide have resulted in more than 9000 citations, including multiple examples
      of important biomedical discoveries. The high (but not perfect) genomic
      similarities between lung cancer cell lines and the lung tumor type from which
      they were derived provide evidence of the relevance of their use. However, major
      problems including misidentification or cell line contamination remain. Ongoing
      studies and new approaches are expected to reveal the full potential of the lung
      cancer cell line panel.

PMID- 20679596
TI  - Impact of common medications on serum total prostate-specific antigen levels:
      analysis of the National Health and Nutrition Examination Survey.
AB  - PURPOSE: Previous studies suggest that some common medications alter prostate
      specific antigen (PSA) levels. It remains unclear whether these reported
      medication effects are due to clinicodemographic factors or concurrent use of
      other medications. We investigated the impact of individual and combinations of
      common medications on PSA in a large cross-sectional study of the United States
      population. PATIENTS AND METHODS: The study included men > or = 40 years old
      without prostate cancer from the 2003 to 2004 and 2005 to 2006 cycles of the
      National Health and Nutrition Examination Survey (NHANES). Men with recent
      prostate manipulation, prostatitis, and those on hormone therapy were excluded.
      Weighted multivariate linear regression was performed on log-transformed total
      PSA to determine the effect of the 10 most commonly prescribed medication
      classes, adjusting for potential confounders including demographics, clinical
      characteristics, physical examination, laboratory studies, and duration of
      medication use. RESULTS: In total, 1,864 men met inclusion criteria. Nonsteroidal
      anti-inflammatory drug (NSAID; P = .03), statin (P = .01), and thiazide diuretic
      (P = .025) intake was inversely related to PSA levels. Five years of NSAID,
      statin, and thiazide diuretic use was associated with PSA levels lower by 6%,
      13%, and 26%, respectively. The combination of statins and thiazide diuretics
      showed the greatest reduction in PSA levels: 36% after 5 years. Concurrent
      calcium channel blocker use minimizes or negates the inverse relationship of
      statin use and PSA level. CONCLUSION: We found that men using NSAIDs, statins,
      and thiazide diuretics have reduced PSA levels by clinically relevant amounts.
      The impact of regularly consuming these common medications on prostate cancer
      screening is unknown.

PMID- 20679597
TI  - Emphysematous colitis of ascending colon with portal venous air caused by diffuse
      large B-cell lymphoma.

PMID- 20679598
TI  - Glucarpidase, leucovorin, and thymidine for high-dose methotrexate-induced renal
      dysfunction: clinical and pharmacologic factors affecting outcome.
AB  - PURPOSE: To assess the role of the recombinant bacterial enzyme, glucarpidase
      (carboxypeptidase-G(2)), leucovorin, and thymidine in the management and outcome
      of patients with high-dose methotrexate (HDMTX) -induced nephrotoxicity. METHODS:
      Patients with HDMTX-induced nephrotoxicity received one to three doses of
      intravenous (IV) glucarpidase and leucovorin rescue. The initial cohort (n = 35)
      also received thymidine by continuous IV infusion. Subsequently, thymidine was
      restricted to patients with prolonged exposure (> 96 hours) to methotrexate (MTX)
      or with substantial MTX toxicity at study entry. Plasma MTX, leucovorin, and 5
      methyltetrahydrofolate (5-mTHF) concentrations were measured pre- and
      postglucarpidase. Toxicities were monitored, and logistic regression analysis was
      used to assess the relationship of baseline characteristics to the development of
      severe toxicity and death. RESULTS: Glucarpidase was administered at a median of
      96 hours (receiving thymidine, n = 44) and 66 hours (not receiving thymidine, n =
      56) after the start of the MTX infusion. Plasma MTX concentrations decreased
      within 15 minutes of glucarpidase by 98.7%. Plasma 5-mTHF concentrations also
      decreased more than 98% after administration of glucarpidase. Of 12 deaths, six
      were directly attributed to irreversible MTX toxicity. Presence of grade 4
      toxicity before administration of glucarpidase, inadequate initial increase in
      leucovorin dosing, and administration of glucarpidase more than 96 hours after
      the start of the MTX infusion were associated with development of grade 4 and 5
      toxicity. CONCLUSION: Early intervention with the combination of leucovorin and
      glucarpidase is highly effective in patients who develop HDMTX-induced renal
      dysfunction. Severe toxicity and mortality occurred in patients in whom
      glucarpidase rescue was delayed and occurred despite thymidine administration.

PMID- 20679599
TI  - Germline genetic variation, cancer outcome, and pharmacogenetics.
AB  - Studies of the role of germline or inherited genetic variation on cancer outcome
      can fall into three distinct categories. First, the impact of highly penetrant
      but lowly prevalent mutations of germline DNA on cancer prognosis has been
      studied extensively for BRCA1 and BRCA2 mutations as well as mutations related to
      hereditary nonpolyposis colorectal cancer syndrome. These mainly modest-sized
      analyses have produced conflicting results. Although some associations have been
      observed, they may not be independent of other known clinical or molecular
      prognostic factors. Second, the impact of germline polymorphisms on cancer
      prognosis is a burgeoning field of research. However, a deeper understanding of
      potentially confounding somatic changes and larger multi-institutional,
      multistage studies may be needed before consistent results are seen. Third,
      research examining the impact of germline genetic variation on differential
      treatment response or toxicity (pharmacogenetics) has produced some proof-of
      principle results. Putative germline pharmacogenetic predictors of outcome
      include DPYD polymorphisms and fluorouracil toxicity, UGT1A1 variation and
      irinotecan toxicity, and CYP2D6 polymorphisms and tamoxifen efficacy, with
      emerging data on predictors of molecularly targeted or biologic drugs. Here we
      review data pertaining to these germline outcome and germline toxicity
      relationships.

PMID- 20679600
TI  - Patient-reported outcomes in sentinel node-negative adjuvant breast cancer
      patients receiving sentinel-node biopsy or axillary dissection: National Surgical
      Adjuvant Breast and Bowel Project phase III protocol B-32.
AB  - PURPOSE: Sentinel lymph node resection (SNR) may reduce morbidity while providing
      the same clinical utility as conventional axillary dissection (AD). National
      Surgical Adjuvant Breast and Bowel Project (NSABP) B-32 is a randomized phase III
      trial comparing SNR immediately followed by AD (SNAD) to SNR and subsequent AD if
      SN is positive. We report the definitive patient-reported outcomes (PRO)
      comparisons. PATIENTS AND METHODS: Eligible patients had clinically node
      negative, operable invasive breast cancer. The PRO substudy included all SN
      negative participants enrolled May 2001 to February 2004 at community
      institutions in the United States (n = 749; 78% age > or = 50; 87% clinical tumor
      size < or = 2.0 cm; 84% lumpectomy; 87% white). They completed questionnaires
      presurgery, 1 and 2 to 3 weeks postoperatively, and every 6 months through year
      3. Arm symptoms, arm use avoidance, activity limitations, and quality of life
      (QOL) were compared with intent-to-treat two-sample t-tests and repeated measures
      analyses. RESULTS: Arm symptoms were significantly more bothersome for SNAD
      compared with SNR patients at 6 months (mean, 4.8 v 3.0; P < .001) and at 12
      months (3.6 v 2.5; P = .006). Longitudinally, SNAD patients were more likely to
      experience ipsilateral arm and breast symptoms, restricted work and social
      activity, and impaired QOL (P < or = .002 all items). From 12 to 36 months, fewer
      than 15% of either SNAD or SNR patients reported moderate or greater severity of
      any given symptom or activity limitation. CONCLUSION: Arm morbidity was greater
      with SNAD than with SNR. Despite considerable fears about complications from AD
      for breast cancer, this study demonstrates that initial problems with either
      surgery resolve over time.

PMID- 20679601
TI  - HIV-associated primary bone marrow Hodgkin's lymphoma: a distinct entity?

PMID- 20679604
TI  - Treatment of cutaneous metastases of Merkel cell carcinoma with surface-mold
      computer-optimized high-dose-rate brachytherapy.

PMID- 20679605
TI  - BRCA1 CpG island hypermethylation predicts sensitivity to poly(adenosine
      diphosphate)-ribose polymerase inhibitors.

PMID- 20679607
TI  - Personalizing therapy in an epidermal growth factor receptor-tyrosine kinase
      inhibitor-resistant non-small-cell lung cancer using PF-00299804 and trastuzumab.

PMID- 20679606
TI  - Relationship between tumor gene expression and recurrence in four independent
      studies of patients with stage II/III colon cancer treated with surgery alone or
      surgery plus adjuvant fluorouracil plus leucovorin.
AB  - PURPOSE: These studies were conducted to determine the relationship between
      quantitative tumor gene expression and risk of cancer recurrence in patients with
      stage II or III colon cancer treated with surgery alone or surgery plus
      fluorouracil (FU) and leucovorin (LV) to develop multigene algorithms to quantify
      the risk of recurrence as well as the likelihood of differential treatment
      benefit of FU/LV adjuvant chemotherapy for individual patients. PATIENTS AND
      METHODS: We performed quantitative reverse transcription polymerase chain
      reaction (RT-qPCR) on RNA extracted from fixed, paraffin-embedded (FPE) tumor
      blocks from patients with stage II or III colon cancer who were treated with
      surgery alone (n = 270 from National Surgical Adjuvant Breast and Bowel Project
      [NSABP] C-01/C-02 and n = 765 from Cleveland Clinic [CC]) or surgery plus FU/LV
      (n = 308 from NSABP C-04 and n = 508 from NSABP C-06). Overall, 761 candidate
      genes were studied in C-01/C-02 and C-04, and a subset of 375 genes was studied
      in CC/C-06. RESULTS: A combined analysis of the four studies identified 48 genes
      significantly associated with risk of recurrence and 66 genes significantly
      associated with FU/LV benefit (with four genes in common). Seven recurrence-risk
      genes, six FU/LV-benefit genes, and five reference genes were selected, and
      algorithms were developed to identify groups of patients with low, intermediate,
      and high likelihood of recurrence and benefit from FU/LV. CONCLUSION: RT-qPCR of
      FPE colon cancer tissue applied to four large independent populations has been
      used to develop multigene algorithms for estimating recurrence risk and benefit
      from FU/LV. These algorithms are being independently validated, and their
      clinical utility is being evaluated in the Quick and Simple and Reliable (QUASAR)
      study.

PMID- 20679608
TI  - Lessons learned from an unusual presentation of CD3+, CD56- T-cell large granular
      lymphocyte leukemia.

PMID- 20679609
TI  - Phase II study of the halichondrin B analog eribulin mesylate in patients with
      locally advanced or metastatic breast cancer previously treated with an
      anthracycline, a taxane, and capecitabine.
AB  - PURPOSE: The activity and safety of eribulin mesylate (E7389), a nontaxane
      microtubule dynamics inhibitor with a novel mechanism of action, were evaluated
      in patients with locally advanced or metastatic breast cancer previously treated
      with an anthracycline, taxane, and capecitabine. PATIENTS AND METHODS: Eligible
      patients in this single-arm, open-label phase II study received eribulin mesylate
      (1.4 mg/m(2)) administered as a 2- to 5-minute intravenous infusion on days 1 and
      8 of a 21-day cycle. The primary end point was objective response rate (ORR)
      assessed by independent review. RESULTS: Of 299 enrolled patients who had
      received a median of four prior chemotherapy regimens, 291 received eribulin (for
      a median of four cycles). Of these, 269 patients met key inclusion criteria for
      the primary efficacy analysis. The primary end point of ORR by independent review
      was 9.3% (95% CI, 6.1% to 13.4%; all partial responses [PRs]), the stable disease
      (SD) rate was 46.5%, and clinical benefit rate (complete response + PR + SD > or
      = 6 months) was 17.1%. The investigator-reported ORR was 14.1% (95% CI, 10.2% to
      18.9%). Median duration of response was 4.1 months, and progression-free survival
      was 2.6 months. Median overall survival was 10.4 months. The most common
      treatment-related grade 3 or 4 toxicities were neutropenia (54%; febrile
      neutropenia, 5.5%), leukopenia (14%), and asthenia/fatigue (10%; no grade 4);
      grade 3 neuropathy occurred in 6.9% of patients (no grade 4). CONCLUSION:
      Eribulin demonstrated antitumor activity in extensively pretreated patients who
      had previously received an anthracycline, taxane, and capecitabine, with a
      manageable tolerability profile.

PMID- 20679610
TI  - Phase II trial of anastrozole plus goserelin in the treatment of hormone receptor
      positive, metastatic carcinoma of the breast in premenopausal women.
AB  - PURPOSE: To explore the antitumor activity of the aromatase inhibitor,
      anastrozole, in the treatment of premenopausal women with hormone receptor
      positive, metastatic breast cancer who have been rendered functionally
      postmenopausal with the use of the luteinizing hormone-releasing hormone agonist,
      goserelin. PATIENTS AND METHODS: Premenopausal women with estrogen and/or
      progesterone receptor-positive, metastatic or recurrent breast cancer were
      enrolled in this prospective, single-arm, multicenter phase II trial. Patients
      were treated with goserelin 3.6 mg subcutaneous monthly and began anastrozole 1
      mg daily 21 days after the first injection of goserelin. Patients continued on
      treatment until disease progression or unacceptable toxicity. RESULTS: Thirty
      five patients were enrolled of which 32 were evaluable for response and toxicity.
      Estradiol suppression was assessed, with mean estradiol levels of 18.7 pg/mL at 3
      months and 14.8 pg/mL at 6 months. One participant (3.1%) experienced a complete
      response, 11 (34.4%) experienced partial response, and 11 (34.4%) experienced
      stable disease for 6 months or longer for a clinical benefit rate of 71.9%.
      Median time to progression was 8.3 months (range, 2.1 to 63+) and median survival
      was not been reached (range, 11.1 to 63+). The most common adverse events were
      fatigue (50%), arthralgias (53%), and hot flashes (59%). There were no grade 4 to
      5 toxicities. CONCLUSION: The combination of goserelin plus anastrozole has
      substantial antitumor activity in the treatment of premenopausal women with
      hormone receptor-positive metastatic breast cancer.

PMID- 20679612
TI  - Multigene assays to improve assessment of recurrence risk and benefit from
      chemotherapy in early-stage colon cancer: has the time finally arrived, or are we
      still stage locked?

PMID- 20679611
TI  - Phase I trial of the irreversible EGFR and HER2 kinase inhibitor BIBW 2992 in
      patients with advanced solid tumors.
AB  - PURPOSE: Preclinical data have demonstrated that BIBW 2992 is a potent
      irreversible inhibitor of ErbB1 (EGFR/HER1) and mutated ErbB1 receptors including
      the T790M variant, as well as ErbB2 (HER2). A phase I study of continuous once
      daily oral BIBW 2992 was conducted to determine safety, maximum-tolerated dose,
      pharmacokinetics (PK), food effect, and preliminary antitumor efficacy. PATIENTS
      AND METHODS: Patients with advanced solid tumors were treated. PK evaluation was
      performed after the first dose and at steady-state. RESULTS: Fifty-three patients
      received BIBW 2992 at 10 to 50 mg/d. BIBW 2992 was generally well-tolerated. The
      most common adverse effects included diarrhea, nausea, vomiting, rash, and
      fatigue. Dose-limiting toxicities included grade 3 rash (n = 2) and reversible
      dyspnea secondary to pneumonitis (n = 1). The recommended phase II dose was 50
      mg/d. PK was dose proportional with a terminal elimination half-life ranging
      between 21.3 and 27.7 hours on day 1 and between 22.3 and 67.0 hours on day 27;
      BIBW 2992 exposure decreased after food intake. Three patients with non-small
      cell lung carcinoma (NSCLC; two with in-frame exon 19 mutation deletions)
      experienced confirmed partial responses (PR) sustained for 24, 18, and 34 months,
      respectively. Two other patients (esophageal carcinoma and NSCLC) had
      nonconfirmed PRs. A patient with a PR at 10 mg/d progressed and developed
      symptomatic brain metastases, which subsequently regressed with an increased dose
      of 40 mg/d of BIBW 2992. A further seven patients had disease stabilization
      lasting > or = 6 months. CONCLUSION: Continuous, daily, oral BIBW 2992 is safe
      and has durable antitumor activity. It is currently being evaluated in phase III
      trials.

PMID- 20679613
TI  - Plasmacytoma of the testis in a patient with previous multiple myeloma: is the
      testis a sanctuary site?

PMID- 20679614
TI  - Trastuzumab-induced cardiotoxicity: clinical and prognostic implications of
      troponin I evaluation.
AB  - PURPOSE: Treatment of breast cancer with trastuzumab is complicated by
      cardiotoxicity in up to 34% of the patients. In most patients, trastuzumab
      induced cardiotoxicity (TIC) is reversible: left ventricular ejection fraction
      (LVEF) improves after trastuzumab withdrawal and with, or sometimes without,
      initiation of heart failure (HF) therapy. The reversibility of TIC, however, is
      not foreseeable, and identification of patients at risk and of those who will not
      recover from cardiac dysfunction is crucial. The usefulness of troponin I (TNI)
      in the identification of patients at risk for TIC and in the prediction of LVEF
      recovery has never been investigated. PATIENTS AND METHODS: In total, 251 women
      were enrolled. TNI was measured before and after each trastuzumab cycle. LVEF was
      evaluated at baseline, every 3 months during trastuzumab therapy, and every 6
      months afterward. In case of TIC, trastuzumab was discontinued, and HF treatment
      with enalapril and carvedilol was initiated. TIC was defined as LVEF decrease of
      > 10 units and below 50%. Recovery from TIC was defined as LVEF increase above
      50%. RESULTS: TIC occurred in 42 patients (17%) and was more frequent in patients
      with TNI elevation (TNI+; 62% v 5%; P < .001). Twenty-five patients (60%)
      recovered from TIC. LVEF recovery occurred less frequently in TNI+ patients (35%
      v 100%; P < .001). At multivariate analysis, TNI+ was the only independent
      predictor of TIC (hazard ratio [HR], 22.9; 95% CI, 11.6 to 45.5; P < .001) and of
      lack of LVEF recovery (HR, 2.88; 95% CI,1.78 to 4.65; P < .001). CONCLUSION: TNI+
      identifies trastuzumab-treated patients who are at risk for cardiotoxicity and
      are unlikely to recover from cardiac dysfunction despite HF therapy.

PMID- 20679615
TI  - Relationship between colorectal cancer biomarkers and response to epidermal
      growth factor receptor monoclonal antibodies.

PMID- 20679617
TI  - Drug development in advanced esophagogastric cancer: the art of extrapolation.

PMID- 20679618
TI  - Clinical value of fluorine-18 2-fluoro-2-deoxy-D-glucose positron emission
      tomography/computed tomography in bladder cancer.
AB  - PURPOSE: Fluorine-18 2-fluoro-2-deoxy-D-glucose (FDG) positron emission
      tomography (PET)/computed tomography (CT) has been approved for imaging in many
      malignancies but not for bladder cancer. This study investigated the value of FDG
      PET/CT imaging in the management of patients with advanced bladder cancer.
      PATIENTS AND METHODS: Between May 2006 and February 2008, 57 patients with
      bladder cancer at our center underwent FDG-PET/CT after CT (n = 52) or magnetic
      resonance imaging (MRI; n = 5). The accuracy of FDG-PET/CT was assessed using
      both organ-based and patient-based analyses. FDG-PET/CT findings were validated
      by either biopsy or serial CT/MRI. Clinician questionnaires performed before and
      after FDG-PET/CT assessed whether those scan results affected management.
      RESULTS: One hundred thirty-five individual lesions were evaluable in 47 patients
      for the organ-based analysis. Overall sensitivity and specificity were 87% (95%
      CI, 76% to 94%) and 88% (95% CI, 78% to 95%), respectively. In the patient-based
      analysis, malignant disease was correctly diagnosed in 25 of 31 patients,
      resulting in a sensitivity of 81% (95% CI, 63% to 93%). FDG-PET/CT was negative
      in 15 of 16 patients without malignant lesions for a specificity of 94% (95% CI,
      71% to 100%). Pre- and post-PET surveys revealed that FDG-PET/CT detected more
      malignant disease than conventional CT/MRI in 40% of patients. Post-PET surveys
      showed that clinicians changed their planned management in 68% of patients based
      on the FDG-PET/CT results. CONCLUSION: FDG-PET/CT has excellent sensitivity and
      specificity in the detection of metastatic bladder cancer and provides additional
      diagnostic information that enhances clinical management more than CT/MRI alone.
      FDG-PET/CT scans may provide better accuracy in clinical information for
      directing therapy.

PMID- 20679619
TI  - Epirubicin, oxaliplatin, and capecitabine with or without panitumumab for
      advanced esophagogastric cancer: dose-finding study for the prospective
      multicenter, randomized, phase II/III REAL-3 trial.
AB  - PURPOSE: Epirubicin, oxaliplatin, and capecitabine (EOC) is a standard treatment
      in advanced esophagogastric cancer. Panitumumab (P) is a fully human,
      immunoglobulin G2 monoclonal antibody targeting epidermal growth factor receptor.
      Randomized Trial of EOC +/- Panitumumab for Advanced and Locally Advanced
      Esophagogastric Cancer (REAL-3) will evaluate whether the addition of P to EOC
      improves survival in patients with advanced esophagogastric adenocarcinoma and
      undifferentiated carcinoma. PATIENTS AND METHODS: The original design of REAL-3
      added P 9 mg/kg to the standard dose of EOC (dose level [DL] + 1). Due to
      toxicity, a dose de-escalation was made to EOC + P DL-1 (epirubicin 50 mg/m(2),
      oxaliplatin130 mg/m(2), capecitabine 1,000 mg/m(2)/d + P 9 mg/kg every 3 weeks).
      After additional toxicity was observed, the study was amended to include two
      additional EOC + P dose levels. Using a 3 + 3 design, dose-limiting toxicities
      (DLTs) were assessed weekly during cycle 1. Patients were randomly assigned 1:1
      to EOC +/- P. RESULTS: Between July 2008 and October 2009, 29 patients were
      randomly selected for standard-dose EOC (n = 13) or EOC + P (n = 16). Five
      patients were treated at DL + 1, with grade 3 diarrhea in four of five patients
      by cycle 4. At DL-1, one patient had grade 3 diarrhea and grade 5 infection.
      Three patients were treated at DL-3, and then six were treated at DL-2, without
      DLTs. CONCLUSION: The recommended dose for EOC + P is epirubicin 50 mg/m(2),
      oxaliplatin 100 mg/m(2), capecitabine 1,000 mg/m(2)/d, and P 9 mg/kg every 3
      weeks. This dose has been selected for the ongoing phase II/III REAL-3 study.

PMID- 20679620
TI  - Vinblastine in children and adolescents with high-risk anaplastic large-cell
      lymphoma: results of the randomized ALCL99-vinblastine trial.
AB  - PURPOSE: The impact of adding vinblastine to a 4-month chemotherapy regimen,
      based on the Non-Hodgkin's Lymphoma Berlin-Frankfurt-Munster 90 protocol, in
      childhood high-risk anaplastic large-cell lymphoma (ALCL) was assessed. PATIENTS
      AND METHODS: Children and adolescents with high-risk ALCL, defined by
      mediastinal, lung, liver, spleen, or skin involvement, were eligible for the
      trial. After a prephase and one chemotherapy course, patients were randomly
      assigned to receive either five further chemotherapy courses without vinblastine
      or the same regimen with one vinblastine injection (6 mg/m(2)) during each course
      followed by weekly vinblastine to complete a total of 1 year of treatment. The
      primary end point was event-free survival (EFS), analyzed on the intent-to-treat
      population. RESULTS: Between November 1999 and June 2006, 110 patients were
      randomly assigned to receive vinblastine, and 107 were randomly assigned not to
      receive vinblastine. Median follow-up was 4.8 years. Patients in the vinblastine
      arm had a significantly reduced risk of events during the first year (hazard
      ratio [HR] = 0.31; 95% CI, 0.15 to 0.67; P = .002) followed by an increased risk
      thereafter (HR = 4.98; 95% CI, 1.65 to 15.0; P = .003). Consequently, EFS at 1
      year differed significantly (91% in the vinblastine group v 74% in the no
      vinblastine group), with no difference at 2 years (73% and 70%, respectively).
      Overall EFS curves did not differ significantly (HR = 0.91; 95% CI, 0.55 to 1.5;
      P = .71). Thirty-one percent of weekly doses of vinblastine were reduced as a
      result of hematologic toxicity, although vinblastine was discontinued for
      toxicity in only three patients. CONCLUSION: Adding vinblastine during induction
      and as maintenance for a total treatment duration of 1 year significantly delayed
      the occurrence of relapses but did not reduce the risk of failure.

PMID- 20679621
TI  - Fatty acid synthase polymorphisms, tumor expression, body mass index, prostate
      cancer risk, and survival.
AB  - PURPOSE: Fatty acid synthase (FASN) regulates de novo lipogenesis, body weight,
      and tumor growth. We examined whether common germline single nucleotide
      polymorphisms (SNPs) in the FASN gene affect prostate cancer (PCa) risk or PCa
      specific mortality and whether these effects vary by body mass index (BMI).
      METHODS: In a prospective nested case-control study of 1,331 white patients with
      PCa and 1,267 age-matched controls, we examined associations of five common SNPs
      within FASN (and 5 kb upstream/downstream, R(2) > 0.8) with PCa incidence and,
      among patients, PCa-specific death and tested for an interaction with BMI.
      Survival analyses were repeated for tumor FASN expression (n = 909). RESULTS:
      Four of the five SNPs were associated with lethal PCa. SNP rs1127678 was
      significantly related to higher BMI and interacted with BMI for both PCa risk
      (P(interaction) = .004) and PCa mortality (P(interaction) = .056). Among
      overweight men (BMI > or = 25 kg/m(2)), but not leaner men, the homozygous
      variant allele carried a relative risk of advanced PCa of 2.49 (95% CI, 1.00 to
      6.23) compared with lean men with the wild type. Overweight patients carrying the
      variant allele had a 2.04 (95% CI, 1.31 to 3.17) times higher risk of PCa
      mortality. Similarly, overweight patients with elevated tumor FASN expression had
      a 2.73 (95% CI, 1.05 to 7.08) times higher risk of lethal PCa (P(interaction) =
      .02). CONCLUSION: FASN germline polymorphisms were significantly associated with
      risk of lethal PCa. Significant interactions of BMI with FASN polymorphisms and
      FASN tumor expression suggest FASN as a potential link between obesity and poor
      PCa outcome and raise the possibility that FASN inhibition could reduce PCa
      specific mortality, particularly in overweight men.

PMID- 20679623
TI  - Unusual presentation of large-cell poorly differentiated neuroendocrine carcinoma
      of the epiglottis.

PMID- 20679624
TI  - TGF-beta1 gene polymorphisms for anticipating radiation-induced pneumonitis in
      non-small-cell lung cancer: different ethnic association.

PMID- 20679625
TI  - Informed decisions regarding microsatellite instability testing: need for an
      intention-to-screen analysis.

PMID- 20679622
TI  - Hepatocellular carcinoma: consensus recommendations of the National Cancer
      Institute Clinical Trials Planning Meeting.
AB  - Hepatocelluar carcinoma (HCC) is the most common primary malignancy of the liver
      in adults and the third most common cause of cancer death worldwide. The
      incidence of HCC in the United States is rising steadily because of the
      prevalence of hepatitis C viral infection and other causes of hepatic cirrhosis.
      The majority of patients have underlying hepatic dysfunction, which complicates
      patient management and the search for safe and effective therapies. The Clinical
      Trials Planning Meeting (CTPM) in HCC was convened by the National Cancer
      Institute's Gastrointestinal Cancer Steering Committee to identify the key
      knowledge gaps in HCC and define clinical research priorities. The CTPM
      structured its review according to current evidence-based treatment modalities in
      HCC and prioritized the recommendations on the basis of the patient populations
      representing the greatest unmet medical need.

PMID- 20679626
TI  - Troponin I provides insight into cardiotoxicity and the anthracycline-trastuzumab
      interaction.

PMID- 20679627
TI  - Child neurology: Migraine with aura in children.
AB  - The differential diagnosis for an acute hemiparesis in a child includes stroke,
      Todd paralysis, and hemiplegic migraine. In the context of an illustrative case,
      this review highlights the differences in clinical presentation among these
      entities and an approach to the diagnostic workup. Migraine with aura in children
      is reviewed, including migraine equivalents such as abdominal migraine and the
      particular presentation of hemiplegic migraine. An approach to the prophylactic
      and acute treatment for children with migraine with aura is offered.

PMID- 20679629
TI  - Teaching NeuroImages: central retinal artery occlusion with cilioretinal artery
      sparing in giant cell arteritis.

PMID- 20679631
TI  - How localized is localization-related epilepsy?

PMID- 20679632
TI  - Postpartum disease activity and breastfeeding in multiple sclerosis revisited.

PMID- 20679633
TI  - Functional connectivity and language impairment in cryptogenic localization
      related epilepsy.
AB  - BACKGROUND: An often underestimated cognitive morbidity in patients with epilepsy
      is language dysfunction. To investigate the neuronal mechanisms underlying
      neuropsychological language impairment, activation maps and functional
      connectivity networks were studied by fMRI of language. METHOD: Fifty-two
      patients with cryptogenic localization-related epilepsy and 27 healthy controls
      underwent neuropsychological assessment of IQ, word fluency, and text reading.
      fMRI was performed with a standard covert word-generation and text-reading
      paradigm. Functional connectivity analysis comprised cross-correlation of signal
      time series of the characteristic and most strongly activated regions involved in
      the language tasks. RESULTS: After careful selection, 34 patients and 20 healthy
      controls were found eligible for analysis. Patients displayed lower IQ, lower
      fluency word count, and lower number of words correctly read compared to
      controls. fMRI activation maps did not differ significantly between patients and
      controls. For the word-generation paradigm, patients with epilepsy had
      significantly lower functional connectivity than controls in the prefrontal
      network. Patients performing worse on the word-fluency test demonstrated a
      significantly lower mean functional connectivity than controls. Text reading
      demonstrated lower functional connectivity in patients with epilepsy in the
      frontotemporal network. Similarly, lower mean functional connectivity was
      observed in patients with lowest reading performance compared to controls. A
      relation between reduced functional connectivity and performance on word-fluency
      and text-reading tests was demonstrated in epilepsy patients. CONCLUSION:
      Impaired performance on language assessment in epilepsy patients is associated
      with loss of functional connectivity in the cognitive language networks.

PMID- 20679634
TI  - OAS1: a multiple sclerosis susceptibility gene that influences disease severity.
AB  - BACKGROUND: Type 1 interferons upregulate oligoadenylate synthetase 1 (OAS1). A
      single nucleotide polymorphism (SNP) in exon 7 of OAS1 results in differential
      RNAseL enzyme activity, the A allele coding for a truncated form with low
      activity and the G conferring high activity. We hypothesized that OAS1 genotypes
      would influence both susceptibility to multiple sclerosis (MS) and disease
      activity with the AA genotype being overrepresented and the GG genotype
      underrepresented in relapsing-remitting MS (RRMS) with increased disease
      activity. METHODS: We examined OAS1 genotype distribution in 401 patients with
      MS, 394 healthy controls, and 178 patients with RRMS receiving interferon-beta
      (IFNbeta) assessed as 1) having no or minimal disease activity on IFNbeta, 2)
      having disease activity despite IFNbeta, and 3) 65 patients with RRMS with highly
      active disease. RESULTS: The OAS1 genotype distribution differed between patients
      with MS and controls (p = 0.000003), with lower frequency of GG homozygotes in
      patients with MS (6%) compared with controls (17%). In relation to disease
      severity, 34 (32%) patients with no or minimal disease activity on IFNbeta had
      the AA and 8 (8%) the GG genotype; of patients with disease activity despite
      IFNbeta, 27 (51%) were AA, while only 1 (2%) was GG (p = 0.03). Median time to
      first relapse on IFNbeta was 24 months in patients with RRMS with AA genotype and
      33 months with AG or GG genotype (p = 0.04). The GG genotype was absent in 65
      patients with highly active RRMS (p = 0.03). CONCLUSIONS: A functional OAS1 SNP,
      AA genotype, confers susceptibility to MS and the GG genotype may protect against
      increased disease activity.

PMID- 20679635
TI  - Open biopsy in patients with acute progressive neurologic decline and absence of
      mass lesion.
AB  - OBJECTIVE: Patients with acute to subacute neurologic decline undergo a battery
      of imaging and laboratory tests to determine a diagnosis and treatment plan.
      Often, after an extensive evaluation, a brain biopsy is recommended as yet
      another tool to assist in determining the diagnosis. The goal of this
      retrospective cohort analysis is to measure the sensitivity of open brain biopsy
      in this patient population, compare these results with the preoperative presumed
      diagnosis, and evaluate if the biopsy result significantly alters treatment.
      METHODS: The authors reviewed the medical records of 135 consecutive patients who
      underwent open brain biopsies for acute to subacute progressive neurologic
      decline between January 1999 and September 2008 at a single institution. All
      patients with mass lesions, with HIV/AIDS, and who were younger than 20 years of
      age were excluded from the study. Fifty-one patients met these criteria and all
      preoperative tests, imaging, and treatment plans were examined and compared with
      postbiopsy interventions to determine the impact of the biopsy on patient
      outcome. RESULTS: The sensitivity of open brain biopsy at our institution was
      35%. The most common preoperative presumed diagnosis was vasculitis and the most
      common postoperative finding was Creutzfeldt-Jakob disease, followed by amyloid
      angiopathy. Postbiopsy hemorrhage was a complication in 4% of patients. Treatment
      plans changed as a direct result of the biopsy in 8% of patients, and in only 4%
      did the biopsy findings make a difference in disease course. CONCLUSION: In
      patients with progressive neurologic decline without a radiographic mass lesion
      or immunodeficiency, open brain biopsy often fails to provide a diagnosis and
      even more rarely does it significantly alter treatment.

PMID- 20679636
TI  - Mild cognitive impairment in clinical care: a survey of American Academy of
      Neurology members.
AB  - OBJECTIVE: To assess how neurologists view mild cognitive impairment (MCI) as a
      clinical diagnosis and how they treat patients with mild cognitive symptoms.
      METHODS: Members of the American Academy of Neurology with an aging, dementia, or
      behavioral neurology practice focus were surveyed by self-administered
      questionnaire. RESULTS: Survey respondents were 420 providers (response rate
      48%), and 88% reported at least monthly encounters with patients experiencing
      mild cognitive symptoms. Most respondents recognize MCI as a clinical diagnosis
      (90%) and use its diagnostic code for billing purposes (70%). When seeing these
      patients, most respondents routinely provide counseling on physical (78%) and
      mental exercise (75%) and communicate about dementia risk (63%); fewer provide
      information on support services (27%) or a written summary of findings (15%).
      Most (70%) prescribe cholinesterase inhibitors at least sometimes for this
      population, with memantine (39%) and other agents (e.g., vitamin E) prescribed
      less frequently. Respondents endorsed several benefits of a diagnosis of MCI: 1)
      involving the patient in planning for the future (87%); 2) motivating risk
      reduction activities (85%); 3) helping with financial planning (72%); and 4)
      prescribing medications (65%). Some respondents noted drawbacks, including 1) too
      difficult to diagnose (23%); 2) better described as early Alzheimer disease
      (21%); and 3) diagnosis can cause unnecessary worry (20%). CONCLUSIONS: Patients
      with mild cognitive symptoms are commonly seen by neurologists, who view MCI as a
      useful diagnostic category. Information and treatments provided to patients with
      MCI vary significantly, suggesting a need for practice guidelines and further
      research on clinical decision-making with this population.

PMID- 20679637
TI  - Impaired interhemispheric inhibition in writer's cramp.
AB  - OBJECTIVES: Reduced cortical inhibition is a feature of focal hand dystonia and
      this likely contributes to excessive muscle contractions. Inhibition from the
      opposite hemisphere, known as interhemispheric inhibition (IHI), was studied
      bidirectionally in 7 right-handed patients with writer's cramp (WC) and age
      matched healthy controls in a cross-sectional physiologic study. METHODS: IHI was
      measured with paired transcranial magnetic stimulation with the conditioning
      stimulus applied to the motor cortex and the test stimulus applied to the
      contralateral motor cortex. Surface EMG was measured in right and left first
      dorsal interosseous muscles during rest, and while holding a pen between the
      thumb and index finger at 20% maximum voluntary contraction with the right
      dystonia-affected hand. The time course and magnitude of IHI was studied at
      interstimulus intervals of 6, 8, 10, 12, 30, 40, and 50 msec between the
      conditioning stimulus and test stimulus. RESULTS: In WC at rest, IHI was
      significantly reduced in the dystonia-affected right hand (IHI from right to left
      motor cortex) at both short (SIHI, 10-12 msec) and long (LIHI, 30-40 msec)
      intervals compared to the unaffected hand. Compared to controls, SIHI and LIHI
      were reduced in the dystonia-affected hand only. There was no difference in IHI
      between controls and WC during the task of holding a pen. CONCLUSIONS: In WC,
      both SIHI and LIHI are reduced in the dystonia-affected hand compared to the
      unaffected hand and to healthy controls. Impaired IHI may contribute to excessive
      muscle contraction in WC.

PMID- 20679639
TI  - Acute and preventive pharmacologic treatment of cluster headache.
AB  - Cluster headache (CH) is a rare and disabling primary headache disorder. CH
      attacks are unilateral, short, severe headaches associated with ipsilateral
      autonomic symptoms that occur in a periodic fashion. We provide a systematic
      review and meta-analysis of existing trials of pharmacotherapy for CH and
      evidence-based suggestions for acute abortive treatment and preventive therapy
      for cluster headache. Prospective, double-blind, randomized controlled trials of
      any pharmacologic agent for the symptomatic relief or prevention of CH were
      included in this evidence-based review. The main outcomes considered were
      headache response and pain-free response at 15 and 30 minutes for acute treatment
      trials, and the cessation of CH attacks within a specific time period or the
      number of days on which CH attacks occurred for preventive trials. Twenty-seven
      trials were included in the analysis. The American Academy of Neurology quality
      criteria were used to assess trial quality and to grade advisements. Based on the
      evidence, for acute treatment of CH, Level A advice can be given for subcutaneous
      sumatriptan 6 mg, zolmitriptan nasal spray 5 mg and 10 mg, and 100% oxygen 6-12
      L/min. Level B advice can be given for sumatriptan nasal spray 20 mg and oral
      zolmitriptan 5 mg and 10 mg. For the prevention of CH, Level B advice can be
      given for intranasal civamide 100 microg daily and suboccipital steroid
      injections, and Level C advice can be given for verapamil 360 mg, lithium 900 mg,
      and melatonin 10 mg.

PMID- 20679638
TI  - Atomoxetine for depression and other neuropsychiatric symptoms in Parkinson
      disease.
AB  - OBJECTIVES: Depression and antidepressant use, especially selective serotonin
      reuptake inhibitors (SSRIs), are common in Parkinson disease (PD). The objective
      of this clinical trial was to assess the efficacy of atomoxetine, a selective
      norepinephrine reuptake inhibitor (SNRI), for the treatment of clinically
      significant depressive symptoms and common comorbid neuropsychiatric symptoms in
      PD. METHODS: A total of 55 subjects with PD and an Inventory of Depressive
      Symptomatology-Clinician (IDS-C) score > or = 22 were randomized to 8 weeks of
      atomoxetine or placebo treatment (target dosage = 80 mg/day). Depression response
      (> 50% decrease in IDS-C score or Clinical Global Impression-Improvement [CGI-I]
      score of 1 or 2) was assessed using intention-to-treat modeling procedures.
      Secondary outcomes included global cognition, daytime sleepiness, anxiety,
      apathy, and motor function. RESULTS: There were no between-groups differences in
      a priori-defined response rates. Using a more liberal response criterion of > 40%
      decrease in IDS score from baseline, there was a trend (p = 0.08) favoring
      atomoxetine. Patients receiving atomoxetine experienced significantly greater
      improvement in global cognition (p = 0.003) and daytime sleepiness (p = 0.001),
      and atomoxetine was well-tolerated. CONCLUSIONS: Atomoxetine treatment was not
      efficacious for the treatment of clinically significant depressive symptoms in
      PD, but was associated with improvement in global cognitive performance and
      daytime sleepiness. Larger studies of SNRIs in PD for disorders of mood,
      cognition, and wakefulness are appropriate. CLASSIFICATION OF EVIDENCE: This
      interventional study provides Class II evidence that atomoxetine (target dosage =
      80 mg/day) is not efficacious in improving clinically significant depression in
      PD.

PMID- 20679640
TI  - Breast-feeding, postpartum and prepregnancy disease activity in multiple
      sclerosis.

PMID- 20679641
TI  - Pott disease causing chin-on-chest deformity and myelopathy.

PMID- 20679642
TI  - Validity of the MoCA and MMSE in the detection of MCI and dementia in Parkinson
      disease.

PMID- 20679643
TI  - Clinical syndromes associated with posterior atrophy: early age at onset AD
      spectrum.

PMID- 20679644
TI  - Lessons on health reform from across the waves.

PMID- 20679645
TI  - Health reform looms as major factor in midterm election battles.

PMID- 20679646
TI  - Renewing primary care: lessons learned from the Spanish health care system.
AB  - From 1978 on, Spain rapidly expanded and strengthened its primary health care
      system, offering a lesson in how to improve health outcomes in a cost-effective
      manner. The nation moved to a tax-based system of universal access for the entire
      population and, at the local level, instituted primary care teams coordinating
      prevention, health promotion, treatment, and community care. Gains included
      increases in life expectancy and reductions in infant mortality, with outcomes
      superior to those in the United States. In 2007 Spain spent $2,671 per person, or
      8.5 percent of its gross domestic product on health care, versus 16 percent in
      the United States. Despite concerns familiar to Americans--about future shortages
      of primary care physicians and relatively low status and pay for these physicians
      -the principles underlying the Spanish reforms offer lessons for the United
      States.

PMID- 20679647
TI  - Incentives could induce Ethiopian doctors and nurses to work in rural settings.
AB  - What would best motivate more doctors and nurses to work in rural areas of poor
      countries, where they are badly needed? We presented doctors and nurses in
      Ethiopia with a series of hypothetical job combinations of wages, working
      conditions, housing benefits, and training opportunities. For doctors, we found
      that higher wages and quality housing incentives had the biggest impact on their
      willingness to practice in towns in rural areas. For nurses, improvements in the
      availability of medical equipment and supplies were the factors most likely to
      bring about a move to a rural village. Choosing the right incentive package
      requires a consideration of both the effects of different packages on health
      workers' choices and the cost of those packages.

PMID- 20679648
TI  - Evaluating the quality of care provided by graduates of international medical
      schools.
AB  - One-quarter of practicing physicians in the United States are graduates of
      international medical schools. The quality of care provided by doctors educated
      abroad has been the subject of ongoing concern. Our analysis of 244,153
      hospitalizations in Pennsylvania found that patients of doctors who graduated
      from international medical schools and were not U.S. citizens at the time they
      entered medical school had significantly lower mortality rates than patients
      cared for by doctors who graduated from U.S. medical schools or who were U.S.
      citizens and received their degrees abroad. The patient population consisted of
      those with congestive heart failure or acute myocardial infarction. We found no
      significant mortality difference when comparing all international medical
      graduates with all U.S. medical school graduates.

PMID- 20679649
TI  - No harm found when nurse anesthetists work without supervision by physicians.
AB  - In 2001 the Centers for Medicare and Medicaid Services (CMS) allowed states to
      opt out of the requirement for reimbursement that a surgeon or anesthesiologist
      oversee the provision of anesthesia by certified registered nurse anesthetists.
      By 2005, fourteen states had exercised this option. An analysis of Medicare data
      for 1999-2005 finds no evidence that opting out of the oversight requirement
      resulted in increased inpatient deaths or complications. Based on our findings,
      we recommend that CMS allow certified registered nurse anesthetists in every
      state to work without the supervision of a surgeon or anesthesiologist.

PMID- 20679650
TI  - Educating health professionals collaboratively for team-based primary care.
AB  - Team-based primary care offers the potential to dramatically improve the quality
      and efficiency of care, but its broader adoption is hindered by an education
      system that trains health professions in silos. Collaborative models that educate
      multiple practitioners together are needed to create a new generation of health
      professionals able to work in efficiently functioning teams. Changes in
      professional cultures, organizational structures, clinical partnerships,
      admissions, accreditation, and funding models will be required to support the
      expansion of collaborative education effectively.

PMID- 20679651
TI  - Beyond the Affordable Care Act: achieving real improvements in Americans' health.
AB  - Improved access to health care is essential if we are to fill the striking gaps
      between how healthy Americans are and how healthy they could be. But access alone
      is not enough. Health and longevity are also profoundly influenced by where and
      how Americans live, learn, work, and play. Recognizing this, the Robert Wood
      Johnson Foundation's Commission to Build a Healthier America has identified
      concrete, feasible actions outside of medical care that constitute an urgent
      agenda for improving America's health. These recommendations require action at
      all levels of society to promote development and health in childhood, good
      nutrition, and communities conducive to good health.

PMID- 20679652
TI  - Why the nation needs a policy push on patient-centered health care.
AB  - The phrase "patient-centered care" is in vogue, but its meaning is poorly
      understood. This article describes patient-centered care, why it matters, and how
      policy makers can advance it in practice. Ultimately, patient-centered care is
      determined by the quality of interactions between patients and clinicians. The
      evidence shows that patient-centered care improves disease outcomes and quality
      of life, and that it is critical to addressing racial, ethnic, and socioeconomic
      disparities in health care and health outcomes. Policy makers need to look beyond
      such areas as health information technology to shape a coordinated and focused
      national policy in support of patient-centered care. This policy should help
      health professionals acquire and maintain skills related to patient-centered
      care, and it should encourage organizations to cultivate a culture of patient
      centeredness.

PMID- 20679653
TI  - Why the affordable care act needs a better name: 'Americare'.
AB  - The culmination of a century's effort to enact universal coverage in the United
      States is a law with an uninspiring title, the Patient Protection and Affordable
      Care Act, and an even more awkward acronym, PPACA. The Obama administration has
      decided to call the legislation the Affordable Care Act, but the expansion of
      health coverage that the law sets in motion has no name, and therefore no
      identity. It badly needs one.

PMID- 20679654
TI  - What the Oregon health study can tell us about expanding Medicaid.
AB  - The recently enacted Patient Protection and Affordable Care Act includes a major
      expansion of Medicaid to low-income adults in 2014. This paper describes the
      Oregon Health Study, a randomized controlled trial that will be able to shed some
      light on the likely effects of such expansions. In 2008, Oregon randomly drew
      names from a waiting list for its previously closed public insurance program. Our
      analysis of enrollment into this program found that people who signed up for the
      waiting list and enrolled in the Oregon Medicaid program were likely to have
      worse health than those who did not. However, actual enrollment was fairly low,
      partly because many applicants did not meet eligibility standards.

PMID- 20679655
TI  - Health plan competition for Medicaid enrollees based on performance does not
      improve quality of care.
AB  - Incentives to improve the quality of care provided in Medicaid managed care plans
      are increasingly common and take many forms. One is a pay-for-performance program
      that automatically assigns new enrollees to better-performing Medicaid plans in
      California. Our qualitative and quantitative study of this program examined the
      expected and actual impacts of the performance incentive on all areas of care. We
      compared quality outcomes in plans included in the pay-for-performance, "auto
      assignment" incentive and comparable outcomes in plans that were not included. We
      found that quality did not improve significantly faster in plans included in the
      incentive scheme. Combined with some evidence of negative impact on other areas
      of care, the findings raise questions about the usefulness of this program in
      California Medicaid, and about similar programs in other states.

PMID- 20679656
TI  - Why some disabled adults in Medicaid face large out-of-pocket expenses.
AB  - Using national survey data, we found that the Medicaid program effectively limits
      out-of-pocket health care spending for the majority of Medicaid enrollees who are
      disabled but are not in institutions, such as nursing homes. However, we also
      found that for 10 percent of these enrollees, annual out-of-pocket spending is
      $1,200 or higher--a significant sum for people who are low-income. Other research
      has shown that such cost barriers can deprive Medicaid enrollees of cost
      effective care in favor of cost-ineffective care or no care at all. As state
      policy makers contemplate benefit reductions that could shift more costs to
      Medicaid enrollees, careful consideration must be given to the potential effects
      on this particularly vulnerable group.

PMID- 20679657
TI  - Little evidence of correlation between growth in health care spending and reduced
      mortality.
AB  - As rapid U.S. health care spending growth continues, the question of whether
      additional dollars purchase better health or unnecessary care remains in sharp
      focus for policy makers, large employers, and other stakeholders. To investigate
      this question, we measured changes in mortality and cost for seven common
      diagnoses at 122 U.S. hospitals from 2000 to 2004. After adjusting for inflation,
      we found little correlation between reduced mortality for certain conditions and
      increased spending on patients with those conditions. The message to be
      underscored once again for policy makers is that health care dollars provide
      inconsistent value, and future spending increases should be targeted to care that
      improves outcomes.

PMID- 20679658
TI  - Cost profiles: should the focus be on individual physicians or physician groups?
AB  - In an effort to rein in rising health care costs, health plans are using
      physician cost profiles as the basis for tiered networks that give patients
      incentives to visit low-cost physicians. Because physician cost profiles are
      often statistically unreliable some experts have argued that physician groups
      should be profiled instead. Using Massachusetts data, we evaluate the two options
      empirically. Although we find that physician-group profiles are statistically
      more reliable, the group profile is not a good predictor of individual physician
      performance within the group. Better methods for creating provider cost profiles
      are needed.

PMID- 20679659
TI  - Ashamed to admit it: owning up to medical error.

PMID- 20679664
TI  - WTX mutations can occur both early and late in the pathogenesis of Wilms tumour.
AB  - BACKGROUND: Somatic mutations in the X-linked tumour suppressor gene WTX have
      been observed in 6- 30% of sporadic cases of Wilms tumour. Germline mutations in
      the same gene cause the sclerosing skeletal dysplasia, osteopathia striata
      congenita with cranial sclerosis (OSCS). No evidence points towards a
      susceptibility to the development of tumours in individuals with OSCS, suggesting
      that there are unrecognised additional determinants that influence the phenotypic
      outcome associated with germline mutations in WTX. One explanation may be that a
      somatic mutation in WTX may need to occur late in tumour development to
      contribute to tumourigenesis. METHODS: Here a panel of four sporadic Wilms
      tumours with associated nephrogenic rest tissue and characterised WTX and CTNNB1
      mutations is studied to ascertain the temporal sequence of acquisition of these
      mutations. Additionally, a family with OSCS is described segregating a germline
      mutation in WTX and manifesting a lethal phenotype in males. One male from this
      family had bilateral multifocal nephrogenic rests at autopsy. RESULTS: In one of
      the four tumours the WTX mutation was present in both tumour and rest tissue
      indicating it had arisen early in tumour development. In the remaining three
      tumours, the WTX mutation was present in the tumour only indicating late
      acquisition of these mutations. CONCLUSIONS: These data indicate that WTX
      mutations can arise both early and late in Wilms tumour development. WTX
      mutations may predispose to nephrogenic rest development rather than Wilms tumour
      per se.

PMID- 20679665
TI  - Guanosine diphosphate-mannose:GlcNAc2-PP-dolichol mannosyltransferase deficiency
      (congenital disorders of glycosylation type Ik): five new patients and seven
      novel mutations.
AB  - BACKGROUND: In type I congenital disorders of glycosylation (CDG I), proteins
      necessary for the biosynthesis of the lipid-linked oligosaccharide (LLO) required
      for protein N-glycosylation are defective. A deficiency in guanosine diphosphate
      mannose: GlcNAc(2)-PP-dolichol mannosyltransferase-1 (MT-1) causes CDG Ik (OMIM
      608540), and only five patients, with severe multisystemic clinical
      presentations, have been described with this disease. Objective To characterise
      genetic, biochemical and clinical data in five new CDG Ik cases and compare these
      findings with those of the five previously described patients. Methods LLO
      biosynthesis was examined in skin biopsy fibroblasts, mannosyltransferases were
      assayed in microsomes prepared from these cells, and ALG1-encoding MT-1 was
      sequenced at the DNA and complementary DNA levels. Clinical data for the five new
      patients were collated. RESULTS: Cells from five patients with non-typed CDG I
      revealed accumulations of GlcNAc(2)-PP-dolichol, the second intermediate in the
      biosynthesis of LLO. Assay of MT-1, -2 and -3, the first three
      mannosyltransferases required for extension of this intermediate, demonstrated
      only MT-1 to be deficient. DNA sequencing of ALG1 revealed nine different
      mutations, seven of which have not been previously reported. Clinical
      presentations are severe, with dysmorphias, CNS involvement and ocular
      disturbances being prevalent. CONCLUSIONS: 5 patients with CDG Ik are described,
      and their identification reveals that in France, this disease and CDG Ib (mannose
      phosphate isomerase deficiency: OMIM 602579) are the most frequently diagnosed
      CDG I after CDG Ia (phosphomannomutase 2 deficiency: OMIM 601785) and
      substantiate previous observations indicating that this disease presents at the
      severe end of the CDG I clinical spectrum.

PMID- 20679666
TI  - Critical consequences of finding three pathogenic mutations in an individual with
      recessive disease.
AB  - The authors report the unexpected finding of three different nonsense mutations
      in two unrelated individuals with a diagnosis of autosomal recessive primary
      microcephaly. In each case one phenotypically normal parent was found to carry
      two of the nonsense mutations, presumably in cis. This finding of 'triple
      pathogenic mutations' is of unknown incidence but has significant implication for
      genetic counselling. A failure to detect all three mutations could result in both
      false positive and false negative diagnoses in other family members. Both of
      these potential problems can be avoided by always genotyping the parents.

PMID- 20679667
TI  - Co-segregation of Norrie disease and idiopathic pulmonary hypertension in a
      family with a microdeletion of the NDP region at Xp11.3-p11.4.
AB  - INTRODUCTION: Norrie disease is a rare X-linked congenital retinal vasculopathy
      that may be accompanied by sensorineural deafness, mental retardation, and other
      neurological deficits. Here we present a family in which Norrie disease co
      segregated with either early-onset idiopathic pulmonary hypertension or sudden
      death preceded by a period of progressive dyspnea. Neither Norrie disease, nor
      its atypical variants described to date, have been associated with this extended
      clinical phenotype. METHODS AND RESULTS: Molecular analysis of the Norrie disease
      gene (NDP) and adjacent loci was performed by multiplex ligation-dependent probe
      amplification and comparative genomic hybridisation. Affected males in this
      family showed an inherited hemizygous deletion restricted to NDP and two
      immediately telomeric genes, monoamine oxidase-B (MAO-B) and monoamine oxidase-A
      (MAO-A), which encode closely related enzymes that metabolize biogenic amines
      including serotonin, dopamine, and norepinephrine. Sequencing of the deletion
      junction showed an unusual pattern in which a region of microhomology flanked
      intervening genomic sequence. CONCLUSION: Because abnormalities of biogenic
      amines, particularly serotonin, have been implicated in the pathophysiology of
      pulmonary hypertension, we propose that presumed MAO deficiency in these patients
      may represent a novel risk factor for pulmonary hypertension, particularly forms
      with very early onset. Fine-mapping of other microdeletions at this locus may
      provide insights into additional mechanisms for nonrecurrent genomic
      rearrangements at this and other chromosomal loci.

PMID- 20679668
TI  - Comparison of abciximab and eptifibatide on angiographic and clinical outcomes in
      rescue percutaneous coronary intervention for failed fibrinolytic therapy.
AB  - BACKGROUND: Adjunctive administration of the glycoprotein IIb/IIIa platelet
      receptor antagonist (GPA), abciximab, improves outcomes in patients undergoing
      rescue percutaneous coronary intervention (PCI). However, it is unknown if other
      GPAs provide a similar benefit in this setting. OBJECTIVE: We sought to compare
      angiographic and clinical outcomes of patients receiving abciximab or
      eptifibatide as an adjunct to rescue PCI. METHODS: In this prospective,
      nonrandomized study, consecutive patients who underwent rescue PCI and received
      adjunctive preprocedural GPA comprised the study population. Thrombolysis in
      myocardial infarction (TIMI) flow, corrected TIMI frame count (CTFC) and
      myocardial blush grade (MBG) were determined before and immediately after rescue
      PCI. Residual ST-segment elevation at 90-120 minutes and peak creatine kinase
      (CK) values for 48 hours after PCI were recorded. Major adverse cardiac events
      (MACE) including death, reinfarction and target vessel revascularization (TVR)
      were determined at discharge, 1 and 6 months. RESULTS: A total of 241 patients
      were included in the study. 162 patients received abciximab and 79 received
      eptifibatide. There were no differences in baseline clinical and angiographic
      characteristics between groups. Post-PCI TIMI flow was similar but post-PCI CTFC
      was significantly lower (17 +/- 10 vs. 22 +/- 18; p = 0.01) and post-PCI MBG
      significantly higher (2.8 +/- 0.5 vs. 2.6 +/- 0.6; p = 0.01) in the abciximab
      group. Patients in the abciximab group had less ST-segment elevation (1.0 +/- 0.9
      vs. 1.5 +/- 1.0 mm; p = 0.003) and lower peak CK (2,484 +/- 2,176 vs. 2,650 +/-
      2,798 U/L; p = 0.001) after PCI. On multivariate analyses, abciximab
      administration (OR = 0.50, CI = 0.26, 0.96; p = 0.03), pre-PCI TIMI 3 flow (OR =
      0.22, CI = 0.05, 0.99; p = 0.04) and female gender (OR = 0.24, CI = 0.08, 0.66; p
      = 0.006) were positive and cardiogenic shock (OR = 2.76, CI = 1.16, 6.58; p =
      0.02) was a negative predictor of normal epicardial perfusion post PCI. Abciximab
      administration (OR = 0.46, CI = 0.24, 0.87; p = 0.02) and pre-PCI CTFC < 25 (OR =
      0.09, CI = 0.02, 0.31, 0.0001) were positive predictors and cardiogenic shock (OR
      = 3.96, CI = 1.55, 10.12; p = 0.004) was a negative predictor of normal
      myocardial perfusion post-PCI as determined by CTFC. Abciximab administration (OR
      = 0.31, CI = 0.15, 0.63; p = 0.001) and pre-PCI MBG 3 (OR = 0.07, CI = 0.02,
      0.23; p < 0.0001) were positive predictors of normal myocardial perfusion post
      PCI as determined by MBG. In-hospital, 1- and 6-month clinical events and MACE
      rates did not differ between groups. CONCLUSIONS: In the setting of rescue PCI,
      adjunctive administration of abciximab resulted in greater improvement in
      angiographic and electrical estimates of myocardial perfusion and smaller infarct
      size compared to eptifibatide. These findings suggest that all GPA may not
      provide equal benefit in rescue PCI.

PMID- 20679669
TI  - Percutaneous transluminal dilatation of inadvertent partial or complete occlusion
      of the femoral artery caused by Angio-Seal deployment for puncture site closure
      after cardiac catheterization.
AB  - BACKGROUND: The use of access-site closure devices in interventional cardiology
      has expanded rapidly in the past several years. Initial reports indicated
      remarkable safety with these devices but there are a small number of major
      complications. This single-center, retrospective study was carried out to
      investigate the efficacy of percutaneous transluminal angioplasty (PTA) of
      inadvertent occlusion or severe stenosis of the femoral artery after deployment
      of the Angio-Seal closure device. From April 1995 to August 2009 a total of 8,587
      Angio-Seal devices were deployed immediately after cardiac catheterization.
      Within 7 days after deployment, clinical signs of acute arterial occlusion or
      severe stenosis of the femoral artery were evident in 6 patients (0.07%). They
      were immediately referred for diagnostic angiography and subsequent PTA.
      Angiography revealed occlusion of the femoral artery at the puncture site level
      in 4 patients and a severe stenosis in 2 patients. Using a cross-over access from
      the opposite groin, PTA of the closed or highly stenosed femoral artery was
      feasible in all cases. At routine follow up 12 months thereafter, there was no
      clinical evidence of symptomatic restenosis. Inadvertent occlusion or high-grade
      stenosis of the femoral artery after Angio-Seal closure device deployment is a
      rare but severe complication. PTA appears to be a safe and effective method of
      treatment, avoiding surgical removal of the plug.

PMID- 20679670
TI  - Unintended consequences of femoral artery closure devices.

PMID- 20679671
TI  - Use of a percutaneous left ventricular assist device for high-risk cardiac
      interventions and cardiogenic shock.
AB  - OBJECTIVE: We sought to describe the use of the TandemHeart percutaneous left
      ventricular assist device (PVAD) in a group of high-risk patients undergoing
      complex cardiovascular procedures. BACKGROUND: There is a substantial risk of
      acute decompensation and death in patients with cardiogenic shock or a reduced
      cardiac reserve undergoing high-risk cardiovascular interventions. The
      TandemHeart PVAD provides near-total hemodynamic support in this setting.
      METHODS: Thirty-seven high-risk patients underwent placement of the TandemHeart
      PVAD during 38 separate procedures between April 2007 and April 2009. PVAD
      insertion was considered emergent if a patient was not expected to survive more
      than 6 hours without PVAD support. Technical success was defined as successful
      initiation of the PVAD and completion of the intended interventional procedure.
      RESULTS: All 37 patients were in cardiogenic shock or undergoing complex coronary
      and valvular interventions with a high probability of hemodynamic collapse. The
      mean (+/- standard deviation) patient age was 73 +/- 14 years; 97% were in either
      NYHA class III-IV heart failure or cardiogenic shock; and the mean EuroSCORE was
      11 +/- 3.4. Indications for ventricular assist device placement included critical
      aortic stenosis (n = 8), severe left main coronary stenosis (n = 18), severe
      multivessel coronary stenosis (n = 19) and severe cardiomyopathy (n = 23). Four
      patients were being managed for fulminant myocarditis, ventricular free-wall
      rupture, flail mitral valve or severe paravalvular leak. Despite their critical
      status and frequent (82%) need for post-procedure blood transfusion, this complex
      and high-risk patient population tolerated PVAD-supported intervention well and
      technical success was achieved in all patients. Seventy-one percent of patients
      survived to hospital discharge with improved functional status. Most deaths
      occurred in patients not expected to survive due to their moribund status and
      multiorgan failure. CONCLUSION: This experience demonstrates the utility and
      effectiveness of TandemHeart PVAD support in patients with advanced disease,
      critical clinical status and limited therapeutic options.

PMID- 20679672
TI  - Veno-arterial ECMO in severe acute right ventricular failure with pulmonary
      obstructive hemodynamic pattern.
AB  - Extracorporeal membrane oxygenation (ECMO) is an effective rescue method for
      severe respiratory and cardiac failure. Right ventricular (RV) failure with
      cardiogenic shock is a critical condition with generally poor prognosis unless
      aggressive therapeutical measures are undertaken. Authors report on their initial
      experience with ECMO support in severe RV failure with cardiogenic shock caused
      by an obstructive hemodynamic pattern. Four patients with cardiogenic shock due
      to severe RV failure related to pulmonary arterial hypertension (2 patients),
      congenital heart disease with Eisenmenger physiology (1 subject) and massive
      pulmonary embolism (1 patient) were supported with emergency veno-arterial ECMO.
      ECMO circuit was instituted using peripheral cannulation in all subjects.
      Immediate hemodynamic and ventilatory improvement was observed in all patients.
      The mean support duration was 11 days (range 5-16 days), 2 (50%) patients were
      successfully weaned off ECMO and survived to hospital discharge. The other 2
      patients were considered by mutual consensus to have irreversible organ damage,
      the ECMO support was withdrawn and the patients died. Bleeding complications were
      the main complications observed. As per initial experience, veno-arterial ECMO
      allows bypassing of the pulmonary bed, therefore, relieves the RV pressure
      overload and does not cause further elevation of the pulmonary pressures in
      contrary to RV assist devices. This aggressive management approach requires
      further clinical evaluation in order to establish its definite role in critical
      RV failure.

PMID- 20679673
TI  - Percutaneous veno-arterial extracorporeal membrane oxygenation: another tool in
      the interventional-heart failure armamentarium.

PMID- 20679674
TI  - Analysis of right radial artery for transradial catheterization by quantitative
      angiography--anatomical consideration of optimal radial puncture point.
AB  - OBJECTIVES: To determine the optimal radial puncture point, we analyzed the
      anatomy and luminal diameter of the right radial artery (RA) by quantitative
      angiography. BACKGROUND: Difficulty of radial puncture has impeded the
      establishment of the transradial approach as the standard procedure for cardiac
      catheterization. METHODS: Antegrade angiography was performed from the right
      brachial artery in 135 patients who underwent coronary angiography. Presence and
      location of a bifurcation in the area of the RA puncture were analyzed.
      Furthermore, inner luminal diameter of the RA was quantitatively measured. We
      used the line between the styloid process and the ulnar styloid process (R-U
      line) as an anatomical reference point. RESULTS: Radial arterial bifurcation with
      a superficial palmar branch was angiographically observed in 66 patients (48.9%).
      The inner luminal diameter was significantly larger at the proximal point to the
      point of bifurcation. The bifurcation level was located at a median of -3.33 mm
      (interquartile range: -5.60 to 4.69 mm) below the R-U line. Radial puncture at 10
      mm proximal to the R-U line could avoid bifurcation in 91.9% of all cases. Mean
      radial, ulnar and brachial arterial inner diameters were 2.94 +/- 0.52 mm, 2.51
      +/- 0.49 mm and 4.53 +/- 0.62 mm. The RA size within 10-60 mm above the R-U line
      was nearly invariable throughout the range. CONCLUSION The radial puncture level
      should be proximal to the radial bifurcation because of its lumen size. The ideal
      puncture point was found to be at least 10 mm proximal to the R-U line.

PMID- 20679675
TI  - The crooked buddy technique: use of a Wiggle wire alongside an extra support wire
      to improve device deliverability.
AB  - The buddy wire is a useful technique for difficult-to-cross lesions that are
      typically identified by poor guide support, vessel tortuosity, calcification
      and/or prior stent placement. We present 5 cases of percutaneous coronary
      interventional success involving difficult-to-cross lesions using the "crooked
      buddy" technique, a unique combination of the Wiggle guidewire as the rail and an
      extra support guidewire as the buddy wire. From our experience, we recommend that
      when difficult-to-cross lesions are identified, moving quickly to the crooked
      buddy technique may avoid unnecessary equipment, contrast and procedure time.

PMID- 20679676
TI  - FDA approval does not mean what you think it does!

PMID- 20679677
TI  - Severe coronary spasm induced by OCT wire. There are no innocuous procedures.

PMID- 20679678
TI  - Current perspectives on carotid revascularization among patients who need cardiac
      surgery.
AB  - Carotid stenosis is often present in patients who need cardiac surgery and is
      predictive of post-operative stroke. A strategy of combined carotid
      endarterectomy and cardiac surgery had been adopted in the past. Staged carotid
      artery stenting prior to cardiac surgery is a less invasive alternative and seems
      to be associated with a lower incidence of stroke and myocardial infarction as
      compared to the combined surgical approach. This article provides a systemic
      review of the management of patients with concomitant carotid and cardiac disease
      requiring cardiac surgical procedure, and will discuss some management issues
      related to carotid stenting in this group of patients. Based on the available
      data, it is perhaps time to revise our practice guidelines by replacing the
      combined surgical strategy with the staged carotid stenting and cardiac surgery
      approach.

PMID- 20679679
TI  - Thrombosuction for procedural acute thrombosis during high-risk carotid
      angioplasty--a case report.
AB  - Carotid endarterectomy in the presence of an occluded contralateral artery is
      associated with a high risk of perioperative stroke. Carotid stenting with
      neuroprotection devices has emerged as a safe procedure for revascularization in
      this circumstance. We performed high-risk carotid angioplasty in a patient with a
      history of recurrent transient ischemic attacks and 90% stenosis of left internal
      carotid artery with other occluded cerebral vessels. The final follow-up
      angiogram revealed thrombotic obstruction of the stent without any evidence of
      vasospasm, stent deformation or dissection. Direct thrombosuction was performed
      with the guiding sheath. Multiple suction passes yielded complete restoration of
      vascular patency and intracranial flows. A control angiogram performed 10 days
      later revealed no residual stenosis or thrombus. Thrombosuction using a guiding
      sheath leads to rapid revascularization in a patient with acute carotid stent
      thrombosis.

PMID- 20679680
TI  - Percutaneous alcohol septal ablation following surgical myectomy.
AB  - BACKGROUND: The management strategy for hypertrophic obstructive cardiomyopathy
      generally begins with medical therapy. When this fails to control symptoms,
      consideration is given to mechanically eliminate the obstruction caused by a
      thickened and bulging interventricular septum to blood flowing out of the left
      ventricle. The literature is abundant with data about the safety and efficacy of
      both surgical myectomy and the newer and now more widely utilized percutaneous
      alcohol septal ablation procedure. Many cases of successful surgical myectomy
      performed on patients with recurrent or residual symptoms following percutaneous
      septal ablation have been published. However, there remains a paucity of
      information available to the clinician faced with a patient with recurrent or
      residual symptoms after undergoing surgical myectomy. METHODS: We were faced with
      a series of 2 such patients who presented to our institution after presumed
      successful myectomy. Both patients had a recurrence of symptoms and a large
      gradient across the left ventricular outflow tract. Both patients were offered
      percutaneous alcohol ablation after failure of medical therapy. RESULTS:
      Excellent results clinically and echocardiographically were achieved in both
      patients, with complete symptom relief reported at follow up. CONCLUSION: We
      offer a review of the literature to date and believe our experience demonstrates
      that percutaneous alcohol septal ablation is an acceptable option that should be
      offered to patients who have recurrent or incomplete relief of symptoms following
      presumed successful surgical myectomy.

PMID- 20679681
TI  - Segmental diastolic compression of venous and arterial conduits post coronary
      artery bypass surgery.
AB  - In a case of constrictive pericarditis post coronary artery bypass surgery we
      describe the diastolic compression of venous and arterial conduits and the timing
      of compression, as demonstrated during angiography, before and after
      pericardiectomy. In conclusion, angiographic demonstration of conduit compression
      is only suggestive of constriction, and consideration of the timing of
      compression during diastole should be a more specific sign.

PMID- 20679682
TI  - ALN inferior vena cava filter upside down rotation with chest caval migration in
      an asymptomatic patient.
AB  - Percutaneous placement of an inferior vena cava (IVC) filter is indicated in
      patients affected by pulmonary embolism or proximal deep venous thrombosis when
      anticoagulation therapy is contraindicated or there is evidence of thromboembolic
      recurrence during anticoagulation. Several complications have been reported using
      IVC filters. Migration is a rare but known and potentially lethal complication of
      IVC filter placement. In this patient, an ALN IVC filter (ALN Implants
      Chirurgicaux Ghisonaccia, France) proximal migration occurred from the inferior
      cava vein to a zone just below the right atrium; it was associated with a
      complete 180 degrees rotation, and we describe here the procedure employed to
      successfully remove this filter.

PMID- 20679683
TI  - Premature coronary artery disease in a patient with glycogen storage disease III.
AB  - The glycogen storage diseases are a rare form of inherited metabolic disease
      affecting intracellular glycogen metabolism, and several studies suggest glycogen
      storage disease (GSD) III predisposes patients to dyslipidemia and endothelial
      dysfunction. The presence of premature atherosclerotic heart disease in patients
      with GSD III has not been reported in the literature. We report a case of a 24-
      year old patient with GSD III admitted with ventricular fibrillation cardiac
      arrest in the setting of anterior wall myocardial infarction. Further studies are
      warranted on the prevalence of atherosclerotic heart disease, and potential
      screening and preventative strategies, in this population of patients potentially
      at-risk for early cardiac events.

PMID- 20679684
TI  - Absent left and right superior vena cava and azygos continuation of inferior vena
      cava: a rare anomaly of systemic venous return.
AB  - We report a case of a complicated vascular access secondary to systemic venous
      defects which have not been previously reported. Further evaluation revealed
      congenital absence of superior vena cava with two brachiocephalic veins draining
      separately. He also had absence of the hepatic segment of the inferior vena cava
      with azygos continuation. The patient did not have congenital anomalies of the
      remaining thoracoabdominal vasculature and viscera.

PMID- 20679685
TI  - Very late thrombosis after subintimal sirolimus-eluting stent implantation during
      percutaneous coronary intervention for chronic total occlusion.
AB  - The clinical significance of late-acquired incomplete stent apposition (ISA)
      after drug-eluting stent (DES) implantation remains controversial. In a case
      report, late-acquired ISA occurred after a DES was implanted into the subintimal
      space during percutaneous coronary intervention (PCI) for chronic total occlusion
      (CTO). However, to our knowledge, there is no report of very late thrombosis of
      such a case. The present case report describes a late-acquired ISA occurring in
      the true lumen side external to the subintimally located sirolimus-eluting stent
      implanted during PCI for a CTO, resulting in very late stent thrombosis (VLST).
      The late-acquired ISA was observed by intravascular ultrasound and optical
      coherence tomography at the time of follow-up angiography after VLST.

PMID- 20679686
TI  - [Biomedical activity of biosurfactants].
AB  - Biosurfactants, amphiphilic compounds, synthesized by microorganisms have
      surface, antimicrobial and antitumor properties. Biosurfactants prevent adhesion
      and biofilms formation by bacteria and fungi on various surfaces. For many years
      microbial surfactants are used as antibiotics with board spectrum of activity
      against microorganisms. Biosurfactants act as antiviral compounds and their
      antitumor activities are mediated through induction of apoptosis. This work
      presents the current state of knowledge related to biomedical activity of
      biosurfactants.

PMID- 20679687
TI  - [The role of the proteasome for therapy of incurable diseases].
AB  - Proteins constitute the basic building elements of living organisms. Proteins
      have a limited lifetime in a cell. The so called "half-life period" of proteins
      is diverse and lasts from several minutes to several days. Regulatory proteins
      appear in a cell for a definite time and are short-lived. The proteins
      responsible for basic cell functions are stable and long-lived. Once their
      functions are fulfilled or because of their surfeit or damage, proteins are
      eliminated by degradation. Transformation processes of proteins are precisely
      controlled. There is also a strict association between protein metabolism and the
      energetic state of a cell. The main proteolytic cell systems are lysosomal and
      proteasome ones. The first (lysosomes) function in a simple and transparent way.
      The second system (proteasomes) is highly organized; by using ubiquitin it
      delivers "molecular label" and sends a marked protein for degradation. Efficient
      degradation of cellular proteins by the UPS route (ubiquitin - proteasome system)
      is essential for signal transduction, transcription adjustment, response to
      stress and control of receptors' activity. The dysfunction of the UPS route is
      crucial in the development of tumors, neurodegenerative diseases and diseases of
      immunological and infectious origin. Therefore, it is a challenge to elaborate
      methods of pharmacological intervention within this system involving, for
      example, the use of specific, low molecular-weight proteasome inhibitors and
      enzymes catalyzing the ubiquitination process. The article presents a review of
      advances in the field, including description of the lysosomal protein degradation
      route, proteasome model, and the phenomenon of protein aggregation. The summary
      of the experience on applied therapies, which use the processes of protein
      degradation as a basis, were also presented.

PMID- 20679688
TI  - [Use of adipose tissue as a source of mesenchymal stem cells].
AB  - Enormous expectations are associated with stem cells with regard to cell therapy
      and tissue engineering. Stem cells have unlimited potential for self-renewal and
      develop into various cell types. For the mesodermal tissue engineering such a
      source of cells is the bone marrow stroma. However, isolation of the bone marrow
      requires general or spinal anesthesia and yields low number of mesodermal stem
      cells (MSCs) upon processing (1 MSC per 105 adherent stromal cells). An
      alternative source of autologous stem cells seems to be, apart from bone marrow:
      periosteum, muscular tissue or synovial membrane and adipose tissue. The adipose
      tissue is derived from the embryonic mesenchyme, contains a large number of
      stromal stem cells and is relatively easy to obtain in large quantities. It
      covers a widespread area of human body, and can be classified as white and brown
      adipose tissue in terms of location and function. Specimens of the adipose tissue
      are usually obtained from elective, laparoscopic or liposuction surgeries.
      Stromal stem cells, isolated from this tissue, exhibit characteristics common to
      mesodermal tissues, including: adherence to plastic, formation of fibroblastic-
      like colonies, extensive proliferative capacity, ability to differentiate into
      several mesodermal lineages (including bone, cartilage, muscle and fat), and
      expression of several common cell surface antigens. Recent evidence suggest that
      these cells can also form non-mesodermal tissues--neuron-like cells. The aim of
      this publication is to describe the application of the adipose tissue as a source
      of mesenchymal stem cells based on current literature data.

PMID- 20679689
TI  - [Pathogenesis and prophylaxis of AMD: focus on oxidative stress and
      antioxidants].
AB  - Age-related macular degeneration (AMD) is the leading cause of severe visual loss
      and blindness in people over 55. Its pathogenesis--likely multifactorial,
      involving a complex interaction of metabolic, functional, genetic and
      environmental factors--remains poorly understood. Among molecular links in
      pathogenesis of AMD is the oxidative stress in the retina, a structure that is
      particularly susceptible to damage by reactive oxygen species (ROS) since
      photoreceptor outer segment (POS) membranes are rich in polyunsaturated fatty
      acids which can be readily oxidized and can initiate a cytotoxic chain reaction.
      Occurring in the neighborhood of photoreceptors, the retinal pigment epithelial
      cells (RPE) actively contribute to both the retinoid cycle and catabolism of
      constantly shed and phagocytized parts of photoreceptor outer segments. Enzymatic
      degradation of photoreceptor fragments occurring in RPE phagolysosomes is not
      complete and undigested material in the form of insoluble aggregates, called
      lipofuscin, is deposited in lysosomes of RPE cells. Lipofuscin contains a mixture
      of diverse molecular components including retinoid-derived compounds, some of
      which displaying potent photoinducible properties, contributing to an enhancement
      and propagation of the oxidative stress. The retina possesses defense mechanisms
      against the oxidative stress that effectively neutralize the consequences of
      reactive oxygen species actions under normal conditions. A key role in the
      antioxidant defense plays an array of substances, including: xanthophylls (lutein
      and zeaxanthin), vitamin C and E, and glutathione. This paper surveys the current
      concepts on the role of the oxidative stress in pathophysiology of AMD, and
      describes major components of the antioxidant defense system, including their use
      in AMD prophylaxis and therapy.

PMID- 20679690
TI  - [Biological activity of poly(ADP-ribose)polymerase-1].
AB  - Poly(ADP-ribose)polymerase-1 (PARP-1) catalyzes the polymerization of ADP-ribose
      units from NAD+ modules on target proteins, resulting in the attachment of linear
      or branched polymers. PARP-1 and its product poly(ADP-ribose)--PAR have recently
      received considerable attention because of their involvement in a wide range of
      cellular processes including chromatin modification, metabolism of nucleic acids,
      transcription regulation, and cell death. This review summarizes recent work on
      modular structure of six functional domains (A-F) of PARP-1 molecule in the
      context of three classic domains, i.e., DNA binding (DBD), automodification (AD)
      and catalytic (CD) released by proteolytic enzymes. A special attention is paid
      to subcellular localization and molecular mechanisms of PARP-1 posttranslational
      modifications, such as: poly(ADP-ribosylation), phosphorylation, acetylation and
      sumolyation. In addition, main functions of PARP-1 are discussed, focusing on the
      activity of this enzyme in DNA damage detection and repair, genome stability, and
      cell death.

PMID- 20679691
TI  - A model-constrained Monte Carlo method for blind arterial input function
      estimation in dynamic contrast-enhanced MRI: I. Simulations.
AB  - Widespread adoption of quantitative pharmacokinetic modeling methods in
      conjunction with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)
      has led to increased recognition of the importance of obtaining accurate patient
      specific arterial input function (AIF) measurements. Ideally, DCE-MRI studies use
      an AIF directly measured in an artery local to the tissue of interest, along with
      measured tissue concentration curves, to quantitatively determine pharmacokinetic
      parameters. However, the numerous technical and practical difficulties associated
      with AIF measurement have made the use of population-averaged AIF data a popular,
      if sub-optimal, alternative to AIF measurement. In this work, we present and
      characterize a new algorithm for determining the AIF solely from the measured
      tissue concentration curves. This Monte Carlo blind estimation (MCBE) algorithm
      estimates the AIF from the subsets of D concentration-time curves drawn from a
      larger pool of M candidate curves via nonlinear optimization, doing so for
      multiple (Q) subsets and statistically averaging these repeated estimates. The
      MCBE algorithm can be viewed as a generalization of previously published methods
      that employ clustering of concentration-time curves and only estimate the AIF
      once. Extensive computer simulations were performed over physiologically and
      experimentally realistic ranges of imaging and tissue parameters, and the impact
      of choosing different values of D and Q was investigated. We found the algorithm
      to be robust, computationally efficient and capable of accurately estimating the
      AIF even for relatively high noise levels, long sampling intervals and low
      diversity of tissue curves. With the incorporation of bootstrapping
      initialization, we further demonstrated the ability to blindly estimate AIFs that
      deviate substantially in shape from the population-averaged initial guess.
      Pharmacokinetic parameter estimates for K(trans), k(ep), v(p) and v(e) all showed
      relative biases and uncertainties of less than 10% for measurements having a
      temporal sampling rate of 4 s and a concentration measurement noise level of
      sigma = 0.04 mM. A companion paper discusses the application of the MCBE
      algorithm to DCE-MRI data acquired in eight patients with malignant brain tumors.

PMID- 20679692
TI  - The use of a reference tissue arterial input function with low-temporal
      resolution DCE-MRI data.
AB  - Pharmacokinetic modeling is a promising quantitative analysis technique for
      cancer diagnosis. However, diagnostic dynamic contrast-enhanced magnetic
      resonance imaging (DCE-MRI) of the breast is commonly performed with low temporal
      resolution. This limits its clinical utility. We investigated for a range of
      temporal resolutions whether pharmacokinetic parameter estimation is impacted by
      the use of data-derived arterial input functions (AIFs), obtained via analysis of
      dynamic data from a reference tissue, as opposed to the use of a standard AIF,
      often obtained from the literature. We hypothesized that the first method allows
      the use of data at lower temporal resolutions than the second method. Test data
      were obtained by downsampling high-temporal-resolution rodent data via a k-space
      based strategy. To fit the basic Tofts model, either the data-derived or the
      standard AIF was used. The resulting estimates of K(trans) and v(e) were compared
      with the standard estimates obtained by using the original data. The deviations
      in K(trans) and v(e), introduced when lowering temporal resolution, were more
      modest using data-derived AIFs compared with using a standard AIF. Specifically,
      lowering the resolution from 5 to 60 s, the respective changes in K(trans) were
      2% (non-significant) and 18% (significant). Extracting the AIF from a reference
      tissue enables accurate pharmacokinetic parameter estimation for low-temporal
      resolution data.

PMID- 20679693
TI  - Accuracy and resolution of THz reflection spectroscopy for medical imaging.
AB  - The use of THz radiation as a potential tool for medical imaging is of increasing
      interest. In this paper three methods of analysis of THz spectroscopic
      information for diagnosis of tissue pathologies at THz frequencies are presented.
      The frequency-dependent absorption coefficients, refractive indices and Debye
      relaxation times of pure water and pure lipids were measured and used as prior
      knowledge in the different theoretical methods for the determination of
      concentration. Three concentration analysis methods were investigated: (a) linear
      spectral decomposition, (b) spectrally averaged dielectric coefficient method and
      (c) the Debye relaxation coefficient method. These methods were validated on
      water and lipid emulsions by determining the concentrations of phantom
      chromophores and comparing to the known composition. The accuracy and resolution
      of each method were determined to assess the potential of each method as a tool
      for medical diagnosis at THz frequencies.

PMID- 20679694
TI  - Noise measurement from magnitude MRI using local estimates of variance and
      skewness.
AB  - In this note, we address the estimation of the noise level in magnitude magnetic
      resonance (MR) images in the absence of background data. Most of the methods
      proposed earlier exploit the Rayleigh distributed background region in MR images
      to estimate the noise level. These methods, however, cannot be used for images
      where no background information is available. In this note, we propose two
      different approaches for noise level estimation in the absence of the image
      background. The first method is based on the local estimation of the noise
      variance using maximum likelihood estimation and the second method is based on
      the local estimation of the skewness of the magnitude data distribution.
      Experimental results on synthetic and real MR image datasets show that the
      proposed estimators accurately estimate the noise level in a magnitude MR image,
      even without background data.

PMID- 20679695
TI  - A model-constrained Monte Carlo method for blind arterial input function
      estimation in dynamic contrast-enhanced MRI: II. In vivo results.
AB  - Accurate quantification of pharmacokinetic model parameters in tracer kinetic
      imaging experiments requires correspondingly accurate determination of the
      arterial input function (AIF). Despite significant effort expended on methods of
      directly measuring patient-specific AIFs in modalities as diverse as dynamic
      contrast-enhanced magnetic resonance imaging (DCE-MRI), dynamic positron emission
      tomography (PET), and perfusion computed tomography (CT), fundamental and
      technical difficulties have made consistent and reliable achievement of that goal
      elusive. Here, we validate a new algorithm for AIF determination, the Monte Carlo
      blind estimation (MCBE) method (which is described in detail and characterized by
      extensive simulations in a companion paper), by comparing AIFs measured in DCE
      MRI studies of eight brain tumor patients with results of blind estimation. Blind
      AIFs calculated with the MCBE method using a pool of concentration-time curves
      from a region of normal brain tissue were found to be quite similar to the
      measured AIFs, with statistically significant decreases in fit residuals observed
      in six of eight patients. Biases between the blind and measured pharmacokinetic
      parameters were the dominant source of error. Averaged over all eight patients,
      the mean biases were +7% in K(trans), 0% in k(ep), -11% in v(p) and +10% in v(e).
      Corresponding uncertainties (median absolute deviation from the best fit line)
      were 0.0043 min(-1) in K(trans), 0.0491 min(-1) in k(ep), 0.29% in v(p) and 0.45%
      in v(e). The use of a published population-averaged AIF resulted in larger mean
      biases in three of the four parameters (-23% in K(trans), -22% in k(ep), -63% in
      v(p)), with the bias in v(e) unchanged, and led to larger uncertainties in all
      four parameters (0.0083 min(-1) in K(trans), 0.1038 min(-1) in k(ep), 0.31% in
      v(p) and 0.95% in v(e)). When blind AIFs were calculated from a region of tumor
      tissue, statistically significant decreases in fit residuals were observed in all
      eight patients despite larger deviations of these blind AIFs from the measured
      AIFs. The observed decrease in root-mean-square fit residuals between the normal
      brain and tumor tissue blind AIFs suggests that the local blood supply in tumors
      is measurably different from that in normal brain tissue and that the proposed
      method is able to discriminate between the two. We have shown the feasibility of
      applying the MCBE algorithm to DCE-MRI data acquired in brain, finding generally
      good agreement with measured AIFs and decreased biases and uncertainties relative
      to the use of a population-averaged AIF. These results demonstrate that the MCBE
      algorithm is a useful alternative to direct AIF measurement in cases where
      acquisition of high-quality arterial input function data is difficult or
      impossible.

PMID- 20679696
TI  - Treatment plan adaptation for MRI-guided radiotherapy using solely MRI data: a CT
      based simulation study.
AB  - An integrated MRI-accelerator system provides MRI images before and during
      irradiation. Our purpose is to investigate the feasibility of treatment plan
      adaptation using solely MRI data, which lack density information. In this study
      we used CT data to quantify the tissue density effect. Treatment planning was
      performed for five prostate cancer patients. We simulated correction of a 3, 5, 7
      and 10 mm prostate shift relative to the body contour in the anterior, posterior,
      superior and inferior directions. We applied the original treatment plan to each
      corrected prostate shift and recalculated the dose distribution using the same
      monitor units (MU). We calculated the dose differences with and without density
      information. The latter mimics geometrically correct MRI data. Physical path
      lengths, available in MRI data, are used to perform MU rescaling per beam and are
      shown to be of more importance than tissue densities for treatment plan
      adaptation in prostate cancer. As the change in the physical path length of the
      central beam axis is representative of the entire beam, MU rescaling based on
      central beam axis information works fine. In conclusion, MRI data could be used
      for treatment plan adaptation in prostate cancer provided that the images are
      geometrically correct.

PMID- 20679697
TI  - Proton range verification using a range probe: definition of concept and initial
      analysis.
AB  - Proton therapy can be particularly sensitive to changes or errors in range. Thus,
      methods for the in vivo measurement of range could be of great use to improve the
      quality and accuracy of proton-based radiotherapy. In this paper, we introduce
      the concept of the 'range probe'. This is a low-dose, high-energy proton pencil
      beam that would pass through a patient, and whose integral Bragg peak would be
      measured on the exit side using a multi-layer detector. We propose that by
      comparing the measured integral Bragg peak with that calculated based on the
      patient's planning CT, such a range probe could provide useful information about
      the accuracy of range calculations in vivo. To study the feasibility of this
      approach, a Monte Carlo-based study has been performed. Using a patient's
      planning CT, MC simulations (VMCpro) have been made for single pencil beams
      laterally traversing the head and stopping in a simulated range telescope behind
      the patient. Range probes have been calculated for different locations, and the
      residual range from the Bragg peak 'signal' in the range telescope has been
      assessed for different assumed detector thicknesses. The sensitivity of this
      approach to changes in CT values, calibration curve and positional shifts of the
      CT have been investigated. From our analysis, range resolutions of 1 mm may be
      possible with a detector thickness of 4 mm for homogeneous regions. Additionally,
      for heterogeneous regions, changes of the Bragg peak shape due to spatial shifts
      of the CT could be a sensitive measure for detecting patient set-up errors
      directly in the treatment position. The concept of the proton 'range probe'
      appears to be feasible for high-resolution range verification. We now want to
      test this concept experimentally using different possible range telescope
      detectors.

PMID- 20679698
TI  - Characterization of controlled bone defects using 2D and 3D ultrasound imaging
      techniques.
AB  - Ultrasound is emerging as an attractive alternative modality to standard x-ray
      and CT methods for bone assessment applications. As of today, however, there is a
      lack of systematic studies that investigate the performance of diagnostic
      ultrasound techniques in bone imaging applications. This study aims at
      understanding the performance limitations of new ultrasound techniques for
      imaging bones in controlled experiments in vitro. Experiments are performed on
      samples of mammalian and non-mammalian bones with controlled defects with size
      ranging from 400 microm to 5 mm. Ultrasound findings are statistically compared
      with those obtained from the same samples using standard x-ray imaging modalities
      and optical microscopy. The results of this study demonstrate that it is feasible
      to use diagnostic ultrasound imaging techniques to assess sub-millimeter bone
      defects in real time and with high accuracy and precision. These results also
      demonstrate that ultrasound imaging techniques perform comparably better than x
      ray imaging and optical imaging methods, in the assessment of a wide range of
      controlled defects both in mammalian and non-mammalian bones. In the future,
      ultrasound imaging techniques might provide a cost-effective, real-time, safe and
      portable diagnostic tool for bone imaging applications.

PMID- 20679699
TI  - Effect of transverse magnetic fields on a simulated in-line 6 MV linac.
AB  - The effects of a transverse magnetic field on an in-line side-coupled 6 MV linear
      accelerator are given. The results are directly applicable to a linac-MR system
      used for real-time image guided adaptive radiotherapy. Our previously designed
      end-to-end linac simulation incorporated the results from the axisymmetric 2D
      electron gun program EGN2w. However, since the magnetic fields being investigated
      are non-axisymmetric in nature for the work presented here, the electron gun
      simulation was performed using OPERA-3d/SCALA. The simulation results from OPERA
      3d/SCALA showed excellent agreement with previous results. Upon the addition of
      external magnetic fields to our fully 3D linac simulation, it was found that a
      transverse magnetic field of 6 G resulted in a 45 +/- 1% beam loss, and by 14 G,
      no electrons were incident on the target. Transverse magnetic fields on the linac
      simulation produced a highly asymmetric focal spot at the target, which
      translated into a 13% profile asymmetry at 6 G. Upon translating the focal spot
      with respect to the target coordinates, profile symmetry was regained at the
      expense of a lateral shift in the dose profiles. It was found that all points in
      the penumbra failed a 1%/1 mm acceptance criterion for fields between 4 and 6 G.
      However, it was also found that the lateral profile shifts were corrected by
      adjusting the jaw positions asymmetrically.

PMID- 20679700
TI  - The impact of morphology on light transport in cancellous bone.
AB  - In recent years, optical techniques based on diffusion approximation have
      demonstrated their ability to gain rich spectral information about bone. However,
      these methods normally assume homogeneity, while cancellous bone and marrow form
      a highly heterogeneous two-phase medium. This paper studies the limitations of
      this assumption, and quantifies the role of microstructure on long-range
      transport properties. The propagation of light pulses through trabecular bone is
      calculated by Monte Carlo simulation of the scattering and absorption in
      reconstructions of bone samples obtained from x-ray micro tomographic scans. The
      time-resolved responses are then fitted with the analytical response of a
      homogeneous material to obtain the apparent transport properties. These
      properties are used to test different homogenization equations that have been
      postulated in the past for heterogeneous tissues and to check their accuracy. The
      results show that nonlinearity and crosstalk between absorption and scattering
      are statistically significant, although their impact is relatively small. More
      importantly, we found that the weight of the components is not only affected by
      their volume fractions, but need to be corrected by other morphologic measures
      like trabecular spacing or connectivity density. These deviations from the
      homogeneous assumption are stronger for scattering than for absorption. In
      conclusion, the average optical properties of cancellous bone are strongly
      determined by its microstructure, meaning that optical techniques are a valid
      method for tissue evaluation, but careful consideration of structure-related
      perturbation sources is required.

PMID- 20679701
TI  - The impact of the waveguide aperture size of the 3D 70 MHz AMC-8 locoregional
      hyperthermia system on tumour coverage.
AB  - The 70 MHz AMC-4 system, with one ring of four waveguides, provides 2D power
      steering. The newly developed AMC-8 system enables 3D steering, using two rings
      of four 70 MHz waveguides. The current waveguide aperture size is 20.2 x 34.3
      cm(2). Waveguides and water boluses cover a large area of the body, which is not
      ideal for short patients. The aim of this study is investigating the impact of
      smaller waveguides on tumour coverage, using treatment planning. Finite
      difference time-domain simulations were performed at 2.5 x 2.5 x 5 mm(3)
      resolution. Virtual AMC-8 systems with waveguide aperture sizes of 20.5 x 34.25,
      17.5 x 34.25, 14.5 x 34.25, 11.5 x 34.25, 8.5 x 34.25 cm(2) and the AMC-4 system
      were modelled. Simulations were performed for elliptical (36 x 24 x 100 cm(3))
      tissue-equivalent phantoms and for five cervical cancer patients. For the
      phantoms S(ratio) (SAR(max_border)/SAR(target)) was evaluated for standard and
      optimized settings. For the patients, temperature distributions were evaluated
      after optimization of tumour temperature, while limiting normal tissue
      temperatures to 45 degrees C. Phantom simulations showed a favourable S(ratio)
      for all two-ring systems, compared to the AMC-4 system, for optimized phase
      amplitude settings. Patient simulations demonstrated that the improvement in
      T(90) for the operational AMC-8 system was approximately 0.5 degrees C. This
      improvement was independent of the aperture size. The average number of imminent
      hot spots and their total volume was almost comparable for 8.5 and 20.5 cm wide
      apertures, but the locations were different. Two-ring waveguide systems with
      eight antennas and aperture sizes in the range from 20.5 x 34.25 cm(2) to 8.5 x
      34.25 cm(2) showed a stable gain in tumour temperature compared to a single-ring
      four-antenna system with 20.5 x 34.25 cm(2) wide apertures.

PMID- 20679702
TI  - RapidArc treatment verification in 3D using polymer gel dosimetry and Monte Carlo
      simulation.
AB  - The aim of this study was to verify the advanced inhomogeneous dose distribution
      produced by a volumetric arc therapy technique (RapidArc) using 3D gel
      measurements and Monte Carlo (MC) simulations. The TPS (treatment planning
      system)-calculated dose distribution was compared with gel measurements and MC
      simulations, thus investigating any discrepancy between the planned dose delivery
      and the actual delivery. Additionally, the reproducibility of the delivery was
      investigated using repeated gel measurements. A prostate treatment plan was
      delivered to a 1.3 liter nPAG gel phantom using one single arc rotation and a
      target dose of 3.3 Gy. Magnetic resonance imaging of the gel was carried out
      using a 1.5 T scanner. The MC dose distributions were calculated using the VIMC
      Arc code. The relative absorbed dose differences were calculated voxel-by-voxel,
      within the volume enclosed by the 90% isodose surface (VOI(90)), for the TPS
      versus gel and TPS versus MC. The differences between the verification methods,
      MC versus gel, and between two repeated gel measurements were investigated in the
      same way. For all volume comparisons, the mean value was within 1% and the
      standard deviation of the differences was within 2.5% (1SD). A 3D gamma analysis
      between the dose matrices were carried out using gamma criteria 3%/3 mm and 5%/5
      mm (% dose difference and mm distance to agreement) within the volume enclosed by
      the 50% isodose surface (VOI(50)) and the 90% isodose surface (VOI(90)),
      respectively. All comparisons resulted in very high pass rates. More than 95% of
      the TPS points were within 3%/3 mm of both the gel measurement and MC simulation,
      both inside VOI(50) and VOI(90). Additionally, the repeated gel measurements
      showed excellent consistency, indicating reproducible delivery. Using MC
      simulations and gel measurements, this verification study successfully
      demonstrated that the RapidArc plan was both accurately calculated and delivered
      as planned.

PMID- 20679703
TI  - Ethyl[tris(3-tert-butyl-5-methylpyrazol-1-yl)hydridoborato]zinc(II).
AB  - The X-ray crystal structure of the title compound,
      [Zn(C(2)H(5))(C(24)H(40)BN(6))], or Tp(tBu,Me)ZnEt [Tp(tBu,Me) is tris(3-tert
      butyl-5-methylpyrazolyl)hydridoborate], reveals a distorted tetrahedral geometry
      around the Zn atom. The Zn center is coordinated by three N atoms of the borate
      ligand and by one C atom of the ethyl group. The present structure and other
      tetrahedral Tp zinc alkyl complexes are compared with similar Ttz ligands (Ttz is
      1,2,4-triazolylborate), but no major differences in the structures are noted, and
      it can be assumed that variation of the substitution pattern of Tp or Ttz ligands
      has little or no influence on the geometry of alkylzinc complexes. Refinement of
      the structure is complicated by a combination of metric pseudosymmetry and
      twinning. The metrics of the structure could also be represented in a double
      volume C-centered orthorhombic unit cell, and the structure is twinned by one of
      the orthorhombic symmetry operators not present in the actual structure. The
      twinning lies on the borderline between pseudomerohedral and nonmerohedral. The
      data were refined as being nonmerohedrally twinned, pseudomerohedrally twinned
      and untwinned. None of the approaches yielded results that were unambiguously
      better than any of the others: the best fit between structural model and data was
      observed using the nonmerohedral approach which also yielded the best structure
      quality indicators, but the data set is less than 80% complete due to rejected
      data. The pseudomerohedral and the untwinned structures are complete, but
      relatively large residual electron densities that are not close to the metal
      center are found with values up to three times higher than in the nonmerohedral
      approach.

PMID- 20679704
TI  - Poly[aqua(mu2-benzene-1,4-dicarboxylato)(mu2-4,4'-bipyridine N,N'
      dioxide)cadmium(II)], a threefold interpenetrating diamond net.
AB  - In the title compound, [Cd(C(8)H(4)O(4))(C(10)H(8)N(2)O(2))(H(2)O)](n), (I), each
      Cd(II) atom is seven-coordinated in a distorted monocapped trigonal prismatic
      coordination geometry, surrounded by four carboxylate O atoms from two different
      benzene-1,4-dicarboxylate (1,4-bdc) anions, two O atoms from two distinct 4,4'
      bipyridine N,N'-dioxide (bpdo) ligands and one water O atom. The Cd(II) atom and
      the water O atom are on a twofold rotation axis. The bpdo and 1,4-bdc ligands are
      on centers of inversion. Each crystallographically unique Cd(II) center is
      bridged by the 1,4-bdc dianions and bpdo ligands to give a three-dimensional
      diamond framework containing large adamantanoid cages. Three identical such nets
      are interlocked with each other, thus directly leading to the formation of a
      threefold interpenetrated three-dimensional diamond architecture. To the best of
      our knowledge, (I) is the first example of a threefold interpenetrating diamond
      net based on both bpdo and carboxylate ligands. There are strong linear O-H...O
      hydrogen bonds between the water molecules and carboxylate O atoms within
      different diamond nets. Each diamond net is hydrogen bonded to its two neighbors
      through these hydrogen bonds, which further consolidates the threefold
      interpenetrating diamond framework.

PMID- 20679705
TI  - Bis[mu3-1,8-bis(triisopropylsilylamido)naphthalene]bis(tetrahydrofuran)di-mu3
      oxido-dimanganese(III)disodium.
AB  - The solid-state structure of the title compound,
      [Na(2)Mn(2)(C(32)H(56)N(2)OSi(2))(2)O(2)] or [1,8
      C(10)H(6)(NSi(i)Pr(3))(2)Mn(mu(3)-O)Na(THF)](2), which lies across a
      crystallographic twofold axis, exhibits a central [Mn(2)O(2)Na(2)](4+) core, with
      two oxide groups, each triply bridging between the two Mn(III) ions and an Na(+)
      ion. Additional coordination is provided to each Mn(III) centre by a 1,8
      C(10)H(6)(NSi(i)Pr(3))(2) [1,8-bis(triisopropylsilylamido)naphthalene] ligand and
      to the Na(+) centres by a tetrahydrofuran molecule. The presence of an additional
      Na...H-C agostic interaction potentially contributes to the distortion around the
      bridging oxide group.

PMID- 20679706
TI  - A new adamantanecarboxylate coordination polymer: poly[[(mu3-adamantane-1,3
      dicarboxylato)aquadioxidouranium(VI)] monohydrate].
AB  - The title compound, {[U(C(12)H(14)O(4))O(2)(H(2)O)] x H(2)O}(n), is the first
      actinide complex featuring adamantanecarboxylate ligands. The metal ion possesses
      a pentagonal-bipyramidal UO(7) coordination involving two axial oxide ligands [U
      O = 1.732 (5) and 1.764 (5) A] and five equatorial O atoms [U-O = 2.259 (5)-2.494
      (4) A] of aqua and carboxylate ligands. The latter display pseudo-chelating and
      bridging coordination modes of the carboxylate groups that are responsible for
      the generation of the centrosymmetric discrete uranium-carboxylate [UO(2)(mu
      RCOO)(2)UO(2)] dimers [U...U = 5.5130 (5) A] and their connection into one
      dimensional chains. Hydrogen bonding involving two coordinated and two solvent
      water molecules [O...O = 2.719 (7)-2.872 (7) A] yields centrosymmetric (H(2)O)(4)
      ensembles and provides noncovalent linkage between the coordination chains to
      generate a three-dimensional network structure.

PMID- 20679707
TI  - Tetrakis(2,2'-bipyridine)-1kappa(4)N,N';4kappa(4)N,N'-{mu4-N,N'-bis[3-(2
      oxidoethylamino)propyl]oxamidato(4-)
      1:2:3:4kappaO:kappa(3)N,N',O':kappa(3)O'',N'',N''':kappaO'''}tetracopper(II)
      tetrakis(perchlorate).
AB  - The title complex, [Cu(4)(C(12)H(22)N(4)O(4))(C(10)H(8)N(2))(4)](ClO(4))(4), has
      a novel tetranuclear copper(II) cation with the oxamidate and ethanolate groups
      of a trans tetraanion of N,N'-bis[3-(hydroxyethylamino)propyl]oxamide (H(4)heap)
      as bridges. The Cu...Cu separation through the oxamide group is 5.1592 (15) A,
      while those through the two ethanolate bridges are 3.3845 (13) and 3.3392 (13) A.
      The two central copper(II) ions are in square-planar N(2)O(2) environments, while
      the two terminal copper(II) ions have distorted N(4)O square-pyramidal
      geometries. The heap(4-) ligand, with an iminoalcohol form, has both an oxamide
      and two ethanolate bridges. Two of the four perchlorate anions are disordered and
      have long contacts with the square-planar Cu(II) ions. The three-dimensional
      structure features arene-perchlorate C-H...O hydrogen bonds and pi-pi stacking.

PMID- 20679708
TI  - Bis(adamantan-1-aminium) tetrachloridozincate(II) 18-crown-6 monohydrate
      clathrate.
AB  - The structure of the title compound [systematic name: bis(adamantan-1-aminium)
      tetrachloridozincate(II)-1,4,7,10,13,16-hexaoxacyclooctadecane-water (1/1/1)],
      (C(10)H(18)N)(2)[ZnCl(4)] x C(12)H(24)O(6) x H(2)O, consists of supramolecular
      rotator-stator assemblies and ribbons of hydrogen bonds parallel to [010]. The
      assemblies are composed of one protonated adamantan-1-aminium cation and one
      crown ether molecule (1,4,7,10,13,16-hexaoxacyclooctadecane) to give an overall
      [(C(10)H(18)N)(18-crown-6)](+) cation. The -NH(3)(+) group of the cation nests in
      the crown and links to the crown-ether O atoms through N-H...O hydrogen bonds.
      The 18-crown-6 ring adopts a pseudo-C(3v) conformation. The second adamantan-1
      aminium forms part of ribbons of adamantan-1-aminium-water-tetrachloridozincate
      units which are interconnected by O-H...Cl, N-H...O and N-H...Cl hydrogen bonds
      via three different continuous rings with R(5)(4)(12), R(4)(3)(10) and R(3)(3)(8)
      motifs.

PMID- 20679709
TI  - [Mu3-cis-N-(2-aminoethyl)-N'-(2-carboxylatophenyl)oxamidato(3-)]bis(2,2'-diamino
      4,4'-bi-1,3-thiazole)tetracopper(II) bis(2,4,6-trinitrophenolate).
AB  - The title complex,
      [Cu(4)(C(11)H(10)N(3)O(4))(2)(C(6)H(6)N(4)S(2))(2)](C(6)H(2)N(3)O(7))(2),
      consists of a circular tetracopper(II) cation with an embedded inversion centre
      and two uncoordinated picrate (2,4,6-trinitrophenolate) anions. The Cu(II)
      cations at the inner sites of N-(2-aminoethyl)-N'-(2
      carboxylatophenyl)oxamidate(3-) (oxbe) have square-planar environments and those
      at the outer sites are in square-pyramidal geometries. The separations of pairs
      of Cu(II) cations bridged by cis-oxamide and carboxylate groups are 5.2217 (5)
      and 5.2871 (5) A, respectively. The tetracopper(II) cations and picrate anions
      are connected by N-H...O hydrogen bonds into a two-dimensional network parallel
      to the (010) plane, and these two-dimensional networks are assembled by two types
      of pi-pi stacking interactions into a three-dimensional supramolecular structure.

PMID- 20679710
TI  - Coordination and hydrogen-bonding assemblies in hybrid reaction products between
      5,10,15,20-tetra-4-pyridylporphyrin and dysprosium trinitrate hexahydrate.
AB  - Reactions of the title free-base porphyrin compound (TPyP) with dysprosium
      trinitrate hexahydrate in different crystallization environments yielded two
      solid products, viz. [mu-5,15-bis(pyridin-1-ium-4-yl)-10,20-di-4
      pyridylporphyrin]bis[aquatetranitratodysprosium(III)] benzene solvate,
      [Dy(2)(NO(3))(8)(C(40)H(28)N(8))(H(2)O)(2)] x C(6)H(6), (I), and 5,10,15,20
      tetrakis(pyridin-1-ium-4-yl)porphyrin pentaaquadinitratodysprosate(III)
      pentanitrate diethanol solvate dihydrate,
      (C(40)H(30)N(8))[Dy(NO(3))(2)(H(2)O)(5)](NO(3))(5) x 2 C(2)H(6)O x 2 H(2)O, (II).
      Compound (I) represents a 2:1 metal-porphyrin coordinated complex, which lies
      across a centre of inversion. Two trans-related pyridyl groups are involved in Dy
      coordination. The two other pyridyl substituents are protonated and involved in
      intermolecular hydrogen bonding along with the metal-coordinated water and
      nitrate ligands. Compound (II) represents an extended hydrogen-bonded assembly
      between the tetrakis(pyridin-1-ium-4-yl)porphyrin tetracation, the
      [Dy(NO(3))(2)(H(2)O)(5)](+) cation and the free nitrate ions, as well as the
      ethanol and water solvent molecules. This report provides the first structural
      characterization of the exocyclic dysprosium complex with tetrapyridylporphyrin.
      It also demonstrates that charge balance can be readily achieved by protonation
      of the peripheral pyridyl functions, which then enhances their capacity in
      hydrogen bonding as H-atom donors rather than H-atom acceptors.

PMID- 20679711
TI  - Poly[dimethyldiphenylphosphonium [di-mu4-iodido-tetra-mu3-iodido
      pentacopper(I)]].
AB  - The title compound, {(C(14)H(16)P)[Cu(5)I(6)]}(n), prepared from the reaction
      between copper powder, iodine and dimethyldiphenylphosphonium iodide in
      hydroxyacetone, features an anion that consists of a continuous two-dimensional
      Cu-I sheet [Cu-I = 2.5960 (14)-2.6994 (13) A and Cu-I-Cu = 63.28 (5)-114.25 (5)
      degrees]. The cation, which lies on a mirror plane, is a typical
      dimethyldiphenylphosphonium ion. The structure shows a strong tendency towards
      segregation of the inorganic and organic parts of the structure into separate
      subspaces. The two-dimensional Cu-I sheet displays a pronounced subcell with
      pseudo-tetragonal symmetry that is broken by ordered vacancies on the Cu
      position. The symmetry is further reduced by the orientation of the interleaved
      organic counter-ion that is inclined with respect to the pseudo-mirror planes
      defined by the Cu-I sheet normal, perpendicular to the b axis.

PMID- 20679712
TI  - Pseudomerohedral twinning, pseudosymmetry and complex hydrogen-bonded sheets in 2
      methoxy-4-(pyrrolo[1,2-a]quinoxalin-4-yl)phenol.
AB  - The title compound, C(18)H(14)N(2)O(2), crystallizes as a nonmerohedral twin, but
      the structure can be satisfactorily refined as a merohedral twin, in which a
      monoclinic unit cell with a cell angle beta close to 90 degrees emulates a
      metrically orthorhombic cell. The two molecules in the asymmetric unit are very
      similar in structure and they are related by an approximate pseudo-screw axis.
      The molecules are linked into complex sheets by a combination of two O-H...N
      hydrogen bonds and four C-H...O hydrogen bonds.

PMID- 20679713
TI  - (9E)-9-benzylidene-3-methyl-2-methylsulfanyl-5-phenyl-5,6,7,8,9,10
      hexahydropyrimido[4,5-b]quinolin-4(3H)-one: polarized molecules within hydrogen
      bonded bilayers.
AB  - The molecules of the title compound, C(26)H(25)N(3)OS, which was prepared by
      means of an acid-catalysed cyclocondensation reaction between a 6
      aminopyrimidinone and 2,6-dibenzylidenecyclohexanone, exhibit a polarized
      electronic structure, namely (9E)-9-benzylidene-3-methyl-2-methylsulfanyl-5
      phenyl-3,5,6,7,8,9-hexahydropyrimido[4,5-b]quinolin-10-ium-4-olate, involving
      charge separation in the vinylogous amide portion. Four hydrogen bonds, two each
      of the C-H...O and C-H...pi(arene) types, link the molecules into bilayers
      comprising inversion-related pairs of sheets, each containing a single type of
      R(4)(3)(36) ring.

PMID- 20679714
TI  - 2-{[(3-Fluorophenyl)amino]methylidene}-3-oxobutanenitrile and 5-{[(3
      fluorophenyl)amino]methylidene}-2,2-dimethyl-1,3-dioxane-4,6-dione: X-ray and DFT
      studies.
AB  - In the crystal structures of the title compounds, C(11)H(9)FN(2)O, (I), and
      C(13)H(12)FNO(4), (II), the molecules are joined pairwise via different hydrogen
      bonds and the constituent pairs are crosslinked by weak C-H...O hydrogen bonds.
      The basic structural motif in (I), which is partially disordered, comprises pairs
      of molecules arranged in an antiparallel fashion which enables C-H...N[triple
      bond]C interactions. The pairs of molecules are crosslinked by two weak C-H...O
      hydrogen bonds. The constituent pair in (II) is formed by intramolecular
      bifurcated C-H...O/O' and combined inter- and intramolecular N-H...O hydrogen
      bonds. In both structures, F atoms form weak C-F...H-C interactions with the H
      atoms of the two neighbouring methyl groups, the H...F separations being
      2.59/2.80 and 2.63/2.71 A in (I) and (II), respectively. The bond orders in the
      molecules, estimated using the natural bond orbitals (NBO) formalism, correlate
      with the changes in bond lengths. Deviations from the ideal molecular geometry
      are explained by the concept of non-equivalent hybrid orbitals. The existence of
      possible conformers of (I) and (II) is analysed by molecular calculations at the
      B3LYP/6-31+G** level of theory.

PMID- 20679715
TI  - Forced twin-chair conformation in 7-benzoyl- and 7-phenylacetyl-r-2,c-4,t-6,t-8
      tetraphenyl-3-thia-7-azabicyclo[3.3.1]nonanes with 1,3-diaxial phenyl groups in
      the piperidine ring: single- and double-layered supramolecular sheets built from
      C-H...O and C-H...pi(arene) hydrogen bonds.
AB  - The crystal structures of 7-benzoyl-r-2,c-4,t-6,t-8-tetraphenyl-3-thia-7
      azabicyclo[3.3.1]nonane, C(38)H(33)NOS, (I), and r-2,c-4,t-6,t-8-tetraphenyl-7
      phenylacetyl-3-thia-7-azabicyclo[3.3.1]nonane [systematic name: 2-phenyl-1-(r-2,c
      4,t-6,t-8-tetraphenyl-3-thia-7-azabicyclo[3.3.1]nonan-7-yl)ethanone],
      C(39)H(35)NOS, (II), both reveal a forced twin-chair conformation with the 1,3
      diaxial phenyl groups in the piperidine ring, and flattening at the N-atom end of
      the piperidine ring of the bicyclic system. In the crystal structure of (I),
      molecules are linked into sheets by a combination of two weak C-H...O and one C
      H...pi(arene) hydrogen bond, while in the crystal structure of (II), the
      molecules extend into double-layered sheets assisted by three C-H...pi(arene)
      hydrogen bonds.

PMID- 20679716
TI  - (S,S)-Lactoyllactic acid and (S,S,S)-lactoyllactoyllactic acid.
AB  - The dimeric condensation product of lactic acid, namely (S,S)-2-[(2
      hydroxypropanoyl)oxy]propanoic acid, C(6)H(10)O(5), (I), crystallizes with two
      independent molecules in the asymmetric unit, which both have an essentially
      planar backbone. The trimeric condensation product, namely (S,S,S)-3-hydroxybut-3
      en-2-yl 2-[(2-hydroxypropanoyl)oxy]propanoate, C(9)H(14)O(7), (II), has one
      molecule in the asymmetric unit and consists of two essentially planar parts,
      with the central C-O bond in a gauche conformation. Both molecules of the dimer
      are involved in intermolecular hydrogen bonds, forming chains with a C(8) graph
      set. These chains are connected by D(2) hydrogen bonds to form a two-dimensional
      layer. The trimer forms hydrogen-bonded C(10) and C(2)(2)(6) chains, which
      together result in a two-dimensional motif. The Hooft method [Hooft, Straver &
      Spek (2008). J. Appl. Cryst. 41, 96-103] was successfully applied to the
      determination of the absolute structure of (I).

PMID- 20679717
TI  - Intermolecular pi-stacking and F...F interactions of fluorine-substituted meso
      alkynylporphyrin.
AB  - Two C2-symmetric meso-alkynylporphyrins, namely 5,15-bis[(4-butyl-2,3,5,6
      tetrafluorophenyl)ethynyl]-10,20-dipropylporphyrin, C(50)H(42)F(8)N(4), (I), and
      5,15-bis[(4-butylphenyl)ethynyl]-10,20-dipropylporphyrin, C(50)H(50)N(4), (II),
      show remarkable pi-pi stacking that forms columns of porphyrin centers. The
      tetrafluorophenylene moieties in (I) show intermolecular interactions with each
      other through the F atoms, forming one-dimensional ribbons. No significant pi-pi
      interactions are observed in the plane of the phenylene and tetrafluorophenylene
      moieties in either (I) or (II). The molecules of both compounds lie about
      inversion centers.

PMID- 20679718
TI  - Graphene-like nets of hydrogen-bonded water molecules in the dihydrate of 2-[(2
      ammonioethyl)amino]acetate and the structure of its anhydrous hydroiodide salt.
AB  - 2-[(2-Ammonioethyl)amino]acetate dihydrate, better known as N-(2
      aminoethyl)glycine dihydrate, C(4)H(10)N(2)O(2) x 2 H(2)O, (I), crystallizes as a
      three-dimensional hydrogen-bonded network. Amino acid molecules form layers in
      the ac plane separated by layers of water molecules, which form a hydrogen-bonded
      two-dimensional net composed of fused six-membered rings having boat
      conformations. The crystal structure of the corresponding hydroiodide salt,
      namely 2-[(2-ammonioethyl)ammonio]acetate iodide, C(4)H(11)N(2)O(2)(+) x I(-),
      (II), has also been determined. The structure of (II) does not accommodate any
      solvent water molecules, and displays stacks of amino acid molecules parallel to
      the a axis, with iodide ions located in channels, resulting in an overall three
      dimensional hydrogen-bonded network structure. N-(2-Aminoethyl)glycine is a
      molecule of considerable biological interest, since its polyamide derivative
      forms the backbone in the DNA mimic peptide nucleic acid (PNA).

PMID- 20679719
TI  - Supramolecular hydrogen-bonded networks in cytosinium nicotinate monohydrate and
      cytosinium isonicotinate cytosine dihydrate.
AB  - The title compounds are proton-transfer compounds of cytosine with nicotinic acid
      [systematic name: 4-amino-2-oxo-2,3-dihydropyrimidin-1-ium nicotinate monohydrate
      (cytosinium nicotinate hydrate), C(4)H(6)N(3)O(+) x C(6)H(4)NO(2)(-) x H(2)O,
      (I)] and isonicotinic acid [systematic name: 4-amino-2-oxo-2,3-dihydropyrimidin-1
      ium isonicotinate-4-aminopyrimidin-2(1H)-one-water (1/1/2) (cytosinium
      isonicotinate cytosine dihydrate), C(4)H(6)N(3)O(+) x C(6)H(4)NO(2)(-) x
      C(4)H(5)N(3)O x 2 H(2)O, (II)]. In (I), the cation and anion are interlinked by N
      H...O hydrogen bonding to form a one-dimensional tape. These tapes are linked
      through water molecules to form discrete double sheets. In (II), the cytosinium
      cytosine base pairs are connected by triple hydrogen bonds, leading to one
      dimensional polymeric ribbons. These ribbons are further interconnected via
      nicotinate-water and water-water hydrogen bonding, resulting in an overall three
      dimensional network.

PMID- 20679720
TI  - (1R,3R,4S)-1-benzyl-3-(tert-butyldimethylsilyloxy)-4-(hydroxymethyl)pyrrolidine
      borane: novel B-H...H-O hydrogen bonding.
AB  - The absolute configuration of the title cis-(1R,3R,4S)-pyrrolidine-borane
      complex, C(18)H(34)BNO(2)Si, was confirmed. Together with the related trans
      isomers (3S,4S) and (3R,4R), it was obtained unexpectedly from the BH(3) x SMe(2)
      reduction of the corresponding chiral (3R,4R)-lactam precursor. The phenyl ring
      is disordered over two conformations in the ratio 0.65:0.35. The crystallographic
      packing is dominated by the rarely found donor-acceptor hydroxy-borane O-H...H-B
      hydrogen bonds.

PMID- 20679721
TI  - The cocrystal nicotinamide-succinic acid (2/1).
AB  - In the asymmetric unit of the crystal structure of nicotinamide-succinic acid
      (2/1), 2C(6)H(6)N(2)O x C(4)H(6)O(4), there are two independent nicotinamide
      molecules in general positions and two half succinic acid molecules which lie
      about inversion centres. The structure contains acid-pyridine and amide-amide
      synthons with nicotinamide molecules forming ladders of alternating R(2)(2)(8)
      and R(4)(2)(8) rings linked through succinic acid to generate a corrugated
      hydrogen-bonded sheet. This sheet is a common supramolecular unit found in other
      2:1 nicotinamide-dicarboxylic acid cocrystals, but the presence of two
      crystallographically distinct nicotinamides with anti and syn conformations,
      forming two distinct sheets within the same structure, is a novel packing feature
      in this type of material.

PMID- 20679722
TI  - 3-Nitrophenol-4,4'-bipyridyl N,N'-dioxide (2/1): a DFT study and CSD analysis of
      DPNO molecular complexes.
AB  - The title 2:1 complex of 3-nitrophenol (MNP) and 4,4'-bipyridyl N,N'-dioxide
      (DPNO), 2C(6)H(5)NO(3) x C(10)H(8)N(2)O(2) or 2MNP.DPNO, crystallizes as a
      centrosymmetric three-component adduct with a dihedral angle of 59.40 (8) degrees
      between the planes of the benzene rings of MNP and DPNO (the DPNO moiety lies
      across a crystallographic inversion centre located at the mid-point of the C-C
      bond linking its aromatic rings). The complex owes its formation to O-H...O
      hydrogen bonds [O...O = 2.605 (3) A]. Molecules are linked by intermolecular C
      H...O and C-H...N interactions forming R(2)(1)(6) and R(2)(2)(10) rings, and
      R(6)(6)(34) and R(4)(4)(26) macro-rings, all of which are aligned along the [1
      01] direction, and R(2)(2)(10) and R(2)(1)(7) rings aligned along the [010]
      direction. The combination of chains of rings along the [1 01] and [010]
      directions generates the three-dimensional structure. A total of 27 systems
      containing the DNPO molecule and forming molecular complexes of an organic nature
      were analysed and compared with the structural characteristics of the dioxide
      reported here. The N-O distance [1.325 (2) A] depends not only on the
      interactions involving the O atom at the N-O group, but also on the structural
      ordering and additional three-dimensional interactions in the crystal structure.
      A density functional theory (DFT) optimized structure at the B3LYP/6-311G(d,p)
      level is compared with the molecular structure in the solid state.

PMID- 20679723
TI  - Donor-acceptor complex of a new bis-TTF donor containing a pyridine diester
      spacer with TCNQ as the acceptor: a disappointing system.
AB  - A new bis-TTF donor (TTF is tetrathiafulvalene) containing a pyridine diester
      spacer, namely bis{2-[(6,7-tetramethylene-3-methylsulfanyltetrathiafulvalen-2
      yl)sulfanyl]ethyl} pyridine-2,6-dicarboxylate-tetracyanoquinodimethane
      dichloromethane (2/1/2), 2C(33)H(33)NO(4)S(12) x C(12)H(4)N(4) x 2 CH(2)Cl(2),
      has been synthesized and its electron-donating ability determined by cyclic
      voltammetry. The electrical conductivity and crystal structure of this donor
      acceptor (DA) complex with TCNQ (tetracyanoquinodimethane) as the acceptor are
      presented. The TCNQ moiety lies across a crystallographic inversion centre. In
      the crystal structure, TTF and TCNQ entities are arranged in alternate stacks;
      this feature, together with the bond lengths of the TCNQ molecule, suggest that
      the expected charge transfer has not occurred and that the D and A entities are
      in the neutral state, in agreement with the poor conductivity of the material
      (sigma(RT) = 2 x 10(-6) S cm(-1)).

PMID- 20679724
TI  - 4-Methoxyanilinium tetrafluoroborate-dibenzo-18-crown-6 (1/1).
AB  - In the structure of the complex of dibenzo-18-crown-6 [systematic name:
      2,5,8,15,18,21-hexaoxatricyclo[20.4.0.0(9,14)]hexacosa-1(26),9,11,13,22,24
      hexaene] with 4-methoxyanilinium tetrafluoroborate, C(7)H(10)NO(+) x BF(4)(-) x
      C(20)H(24)O(6), the protonated 4-methoxyanilinium (MB-NH(3)(+)) cation forms a
      1:1 supramolecular rotator-stator complex with the dibenzo-18-crown-6 molecule
      via N-H...O hydrogen bonds. The MB-NH(3)(+) group is attached from the convex
      side of the bowl-shaped crown, in contrast with similar ammonium cations that
      nest in the curvature of the bowl. The cations are associated via C-H...pi
      interactions, while the cations and anions are linked by weak C-H...F hydrogen
      bonds, forming cation-crown-anion chains parallel to [011].

PMID- 20679725
TI  - Z and E isomers of butenedioic acid with 2-amino-1,3-thiazole: 2-amino-1,3
      thiazolium hydrogen maleate and 2-amino-1,3-thiazolium hydrogen fumarate.
AB  - Maleic acid and fumaric acid, the Z and E isomers of butenedioic acid, form 1:1
      adducts with 2-amino-1,3-thiazole, namely 2-amino-1,3-thiazolium hydrogen maleate
      (2ATHM), C(3)H(5)N(2)S(+) x C(4)H(3)O(4)(-), and 2-amino-1,3-thiazolium hydrogen
      fumarate (2ATHF), C(3)H(5)N(2)S(+) x C(4)H(3)O(4)(-), respectively. In both
      compounds, protonation of the ring N atom of the 2-amino-1,3-thiazole and
      deprotonation of one of the carboxyl groups are observed. The asymmetric unit of
      2ATHF contains three independent ion pairs. The hydrogen maleate ion of 2ATHM
      shows a short intramolecular O-H...O hydrogen bond with an O...O distance of
      2.4663 (19) A. An extensive hydrogen-bonded network is observed in both
      compounds, involving N-H...O and O-H...O hydrogen bonds. 2ATHM forms two
      dimensional sheets parallel to the ab plane, extending as independent parallel
      sheets along the c axis, whereas 2ATHF forms two-dimensional zigzag layers
      parallel to the bc plane, extending as independent parallel layers along the a
      axis.

PMID- 20679726
TI  - CTGF directs fibroblast differentiation from human mesenchymal stem/stromal cells
      and defines connective tissue healing in a rodent injury model.
AB  - Fibroblasts are ubiquitous cells that demonstrate remarkable diversity. However,
      their origin and pathways of differentiation remain poorly defined. Here, we show
      that connective tissue growth factor (CTGF; also known as CCN2) is sufficient to
      induce human bone marrow mesenchymal stem/stromal cells (MSCs) to differentiate
      into fibroblasts. CTGF-stimulated MSCs lost their surface mesenchymal epitopes,
      expressed broad fibroblastic hallmarks, and increasingly synthesized collagen
      type I and tenacin-C. After fibroblastic commitment, the ability of MSCs to
      differentiate into nonfibroblastic lineages - including osteoblasts,
      chondrocytes, and adipocytes - was diminished. To address inherent heterogeneity
      in MSC culture, we established 18 single MSC-derived clones by limiting dilution.
      CTGF-treated MSCs were alpha-SMA-, differentiating into alpha-SMA+ myofibroblasts
      only when stimulated subsequently with TGF-beta1, suggestive of stepwise
      processes of fibroblast commitment, fibrogenesis, and pathological fibrosis. In
      rats, in vivo microencapsulated delivery of CTGF prompted postnatal connective
      tissue to undergo fibrogenesis rather than ectopic mineralization. The knowledge
      that fibroblasts have a mesenchymal origin may enrich our understanding of organ
      fibrosis, cancer stroma, ectopic mineralization, scarring, and regeneration.

PMID- 20679728
TI  - An alphavirus vector overcomes the presence of neutralizing antibodies and
      elevated numbers of Tregs to induce immune responses in humans with advanced
      cancer.
AB  - Therapeutic anticancer vaccines are designed to boost patients' immune responses
      to tumors. One approach is to use a viral vector to deliver antigen to in situ
      DCs, which then activate tumor-specific T cell and antibody responses. However,
      vector-specific neutralizing antibodies and suppressive cell populations such as
      Tregs remain great challenges to the efficacy of this approach. We report here
      that an alphavirus vector, packaged in virus-like replicon particles (VRP) and
      capable of efficiently infecting DCs, could be repeatedly administered to
      patients with metastatic cancer expressing the tumor antigen carcinoembryonic
      antigen (CEA) and that it overcame high titers of neutralizing antibodies and
      elevated Treg levels to induce clinically relevant CEA-specific T cell and
      antibody responses. The CEA-specific antibodies mediated antibody-dependent
      cellular cytotoxicity against tumor cells from human colorectal cancer
      metastases. In addition, patients with CEA-specific T cell responses exhibited
      longer overall survival. These data suggest that VRP-based vectors can overcome
      the presence of neutralizing antibodies to break tolerance to self antigen and
      may be clinically useful for immunotherapy in the setting of tumor-induced
      immunosuppression.

PMID- 20679727
TI  - Rb deletion in mouse mammary progenitors induces luminal-B or basal-like/EMT
      tumor subtypes depending on p53 status.
AB  - Breast cancer is a highly heterogeneous disease, with several different subtypes
      being characterized by distinct histology, gene expression patterns, and genetic
      alterations. The tumor suppressor gene retinoblastoma 1 (RB1) is frequently lost
      in both luminal-B and triple-negative tumor (TNT; i.e., estrogen receptor-,
      progesterone receptor-, and human epidermal growth factor receptor 2-negative)
      breast cancer subtypes. However, a causal role for RB1 loss in different subtypes
      remains undefined. Here we report that deletion of Rb alone or together with its
      relative p107 in mouse mammary stem/bipotent progenitor cells induced focal
      acinar hyperplasia with squamous metaplasia. These lesions progressed into
      histologically diverse, transplantable mammary tumors with features of either
      luminal-B or TNT subtypes. The TNTs included basal-like tumors as well as tumors
      that exhibited epithelial-to-mesenchymal transition (EMT). The EMT-type tumors
      and a subset of the basal-like tumors, but not luminal-B-like tumors, expressed
      mutant forms of the tumor suppressor p53. Accordingly, targeted deletion of both
      Rb and p53 in stem/bipotent progenitors led to histologically uniform,
      aggressive, EMT-type tumors. Reintroduction of Rb into these tumor cells
      suppressed growth in vitro and tumor formation in vivo. These results establish a
      causal role for Rb loss in breast cancer in mice and demonstrate that cooperating
      oncogenic events, such as mutations in p53, dictate tumor subtype after Rb
      inactivation.

PMID- 20679729
TI  - Increased catecholamine secretion contributes to hypertension in TRPM4-deficient
      mice.
AB  - Hypertension is an underlying risk factor for cardiovascular disease. Despite
      this, its pathogenesis remains unknown in most cases. Recently, the transient
      receptor potential (TRP) channel family was associated with the development of
      several cardiovascular diseases linked to hypertension. The melastatin TRP
      channels TRPM4 and TRPM5 have distinct properties within the TRP channel family:
      they form nonselective cation channels activated by intracellular calcium ions.
      Here we report the identification of TRPM4 proteins in endothelial cells, heart,
      kidney, and chromaffin cells from the adrenal gland, suggesting that they have a
      role in the cardiovascular system. Consistent with this hypothesis, Trpm4 gene
      deletion in mice altered long-term regulation of blood pressure toward
      hypertensive levels. No changes in locomotor activity, renin-angiotensin system
      function, electrolyte and fluid balance, vascular contractility, and cardiac
      contractility under basal conditions were observed. By contrast, inhibition of
      ganglionic transmission with either hexamethonium or prazosin abolished the
      difference in blood pressure between Trpm4-/- and wild-type mice. Strikingly,
      plasma epinephrine concentration as well as urinary excretion of catecholamine
      metabolites were substantially elevated in Trpm4-/- mice. In freshly isolated
      chromaffin cells, lack of TRPM4 was shown to cause markedly more acetylcholine
      induced exocytotic release events, while neither cytosolic calcium concentration,
      size, nor density of vesicles were different. We therefore conclude that TRPM4
      proteins limit catecholamine release from chromaffin cells and that this
      contributes to increased sympathetic tone and hypertension.

PMID- 20679730
TI  - Mice deficient in MCT8 reveal a mechanism regulating thyroid hormone secretion.
AB  - The mechanism of thyroid hormone (TH) secretion from the thyroid gland into blood
      is unknown. Humans and mice deficient in monocarboxylate transporter 8 (MCT8)
      have low serum thyroxine (T4) levels that cannot be fully explained by increased
      deiodination. Here, we have shown that Mct8 is localized at the basolateral
      membrane of thyrocytes and that the serum TH concentration is reduced in Mct8-KO
      mice early after being taken off a treatment that almost completely depleted the
      thyroid gland of TH. Thyroid glands in Mct8-KO mice contained more non
      thyroglobulin-associated T4 and triiodothyronine than did those in wild-type
      mice, independent of deiodination. In addition, depletion of thyroidal TH content
      was slower during iodine deficiency. After administration of 125I, the rate of
      both its secretion from the thyroid gland and its appearance in the serum as
      trichloroacetic acid-precipitable radioactivity was greatly reduced in Mct8-KO
      mice. Similarly, the secretion of T4 induced by injection of thyrotropin was
      reduced in Mct8-KO in which endogenous TSH and T4 were suppressed by
      administration of triiodothyronine. To our knowledge, this study is the first to
      demonstrate that Mct8 is involved in the secretion of TH from the thyroid gland
      and contributes, in part, to the low serum T4 level observed in MCT8-deficient
      patients.

PMID- 20679732
TI  - Serine protease activity contributes to control of Mycobacterium tuberculosis in
      hypoxic lung granulomas in mice.
AB  - The hallmark of human Mycobacterium tuberculosis infection is the presence of
      lung granulomas. Lung granulomas can have different phenotypes, with caseous
      necrosis and hypoxia present within these structures during active tuberculosis.
      Production of NO by the inducible host enzyme NOS2 is a key antimycobacterial
      defense mechanism that requires oxygen as a substrate; it is therefore likely to
      perform inefficiently in hypoxic regions of granulomas in which M. tuberculosis
      persists. Here we have used Nos2-/- mice to investigate host-protective
      mechanisms within hypoxic granulomas and identified a role for host serine
      proteases in hypoxic granulomas in determining outcome of disease. Nos2-/- mice
      reproduced human-like granulomas in the lung when infected with M. tuberculosis
      in the ear dermis. The granulomas were hypoxic and contained large amounts of the
      serine protease cathepsin G and clade B serine protease inhibitors (serpins).
      Extrinsic inhibition of serine protease activity in vivo resulted in distorted
      granuloma structure, extensive hypoxia, and increased bacterial growth in this
      model. These data suggest that serine protease activity acts as a protective
      mechanism within hypoxic regions of lung granulomas and present a potential new
      strategy for the treatment of tuberculosis.

PMID- 20679733
TI  - Synergistic dual automaticity in sinoatrial node cell and tissue models.
AB  - BACKGROUND: The mechanism of sinoatrial node (SAN) automaticity is traditionally
      attributed to membrane ion currents. Recent evidence indicates spontaneous
      sarcoplasmic reticulum (SR) Ca(2+) cycling also plays an important role. METHODS
      AND RESULTS: A computer simulation on SAN cell and 1D tissue model was performed.
      In the SAN cells, SR Ca(2+) cycling broadly modulated the sinus rate from 1.74 Hz
      to 3.87 Hz. Shortening of the junctional SR refilling time and increase of SR
      Ca(2+) release were responsible for sinus rate acceleration. However, under the
      fast SR Ca(2+) cycling, decreased L-type Ca(2+) current (I(CaL)) resulted in
      irregular firing. When Ca(2+) cycling was suppressed, I(f) and I(CaT) both acted
      to stabilize the pacemaker rhythm, but I(CaT) had less effect than I(f). At the
      1D level, the electrical coupling between neighboring cells had little effect on
      the earliest pacemaker location. The leading pacemaking site always colocalized
      with the site with the highest SR Ca(2+) cycling rate, but shifted to the site
      with less inhibited I(CaL). CONCLUSIONS: The rate of SR Ca(2+) cycling can
      effectively and broadly modulate the sinus rate. I(f), I(CaL) and I(CaT) play
      integral roles to guarantee SAN cell rhythmic firing. The leading pacemaker site
      is determined by intracellular Ca(2+) dynamics and membrane currents, indicating
      the synergistic dual automaticity not only exists in single SAN cells, but also
      at the tissue level. 

PMID- 20679731
TI  - Reconstruction of the complete human cytomegalovirus genome in a BAC reveals RL13
      to be a potent inhibitor of replication.
AB  - Human cytomegalovirus (HCMV) in clinical material cannot replicate efficiently in
      vitro until it has adapted by mutation. Consequently, wild-type HCMV differ
      fundamentally from the passaged strains used for research. To generate a
      genetically intact source of HCMV, we cloned strain Merlin into a self-excising
      BAC. The Merlin BAC clone had mutations in the RL13 gene and UL128 locus that
      were acquired during limited replication in vitro prior to cloning. The complete
      wild-type HCMV gene complement was reconstructed by reference to the original
      clinical sample. Characterization of viruses generated from repaired BACs
      revealed that RL13 efficiently repressed HCMV replication in multiple cell types;
      moreover, RL13 mutants rapidly and reproducibly emerged in transfectants. Virus
      also acquired mutations in genes UL128, UL130, or UL131A, which inhibited virus
      growth specifically in fibroblast cells in wild-type form. We further report that
      RL13 encodes a highly glycosylated virion envelope protein and thus has the
      potential to modulate tropism. To overcome rapid emergence of mutations in
      genetically intact HCMV, we developed a system in which RL13 and UL131A were
      conditionally repressed during virus propagation. This technological advance now
      permits studies to be undertaken with a clonal, characterized HCMV strain
      containing the complete wild-type gene complement and promises to enhance the
      clinical relevance of fundamental research on HCMV.

PMID- 20679734
TI  - Volumetric analysis of coronary plaque characterization in patients with
      metabolic syndrome using 64-slice multi-detector computed tomography.
AB  - BACKGROUND: Metabolic syndrome (MetS) is associated with adverse cardiovascular
      events and mortality, where acute coronary syndrome significantly impacts on
      mortality and morbidity. In contrast, evidences have accumulated that the lipid
      rich plaque might play a critical role in acute coronary syndrome. METHODS AND
      RESULTS: The study population consisted of 94 patients with suspected angina
      pectoris who underwent multi-detector computed tomography (MDCT). Of those, we
      identified 41 with MetS. In MDCT analysis, low-density plaque volume (LDPV) (42
      +/- 28 vs 24 +/- 18 mm(3), P=0.0003), moderate-density plaque volume (105 +/- 41
      vs 82 +/- 33 mm(3), P=0.003), total plaque volume (164 +/- 70 vs 118 +/- 59
      mm(3), P=0.0008) and %LDPV (24.2 +/- 10.0 vs 18.3 +/- 7.1%, P=0.01) were
      significantly increased in the MetS group compared to the non-MetS group.
      Multivariate linear regression analysis after adjusting for confounding variables
      revealed that MetS was significantly correlated with an increase in %LDPV
      (beta=0.48, P=0.0001). Multivariate logistic regression analysis for lipid-rich
      plaque after adjusting for confounding variables indicated that MetS was
      significantly associated with lipid-rich plaque (odds ratio: 5.99, 95% confidence
      intervals: 1.94-18.6, P=0.002). CONCLUSIONS: Patients with MetS were strongly
      related to having a lipid-rich composition in their coronary plaque, as detected
      by MDCT. 

PMID- 20679735
TI  - Predictors of electrical storm in patients with idiopathic dilated cardiomyopathy
      -how to stratify the risk of electrical storm.
AB  - BACKGROUND: Electrical storm (ES) is a serious problem in patients with an
      implantable cardioverter defibrillator (ICD). However, insufficient reports have
      indicated the predictors of ES in ICD patients with idiopathic dilated
      cardiomyopathy (DCM). The purpose of this study was to clarify the predictors of
      ES for risk stratification in DCM patients with an ICD. METHODS AND RESULTS: Of
      446 ICD patients, 53 DCM patients were included in this study. During a mean
      follow-up of 55+/-36 months, ES (> or =3 times appropriate ICD therapy within 24
      h) occurred in 18/53 (34%) patients. According to multivariate Cox proportional
      hazard regression analysis, a duration of the terminal low amplitude signals of
      <40 microV (LAS40) (HR 1.4/10 ms increase, 95% confidence interval (CI) 1.1-2.1;
      P=0.0049) or root mean square voltage of the last 40 ms of the QRS complex
      (RMS40) (HR 0.88/1 microV, 95%CI 0.77-0.96; P=0.001) on the signal averaged
      electrocardiogram, and a history of atrial fibrillation (AF) before ICD
      implantation (HR 2.3, 95%CI 1.2-5.0; P=0.013) were independently associated with
      an increased risk of ES. CONCLUSIONS: Our data indicated that a longer LAS40,
      lower RMS40 and history of AF before ICD implantation could strongly predict ES,
      and the combination of those parameters could effectively stratify the risk of ES
      in DCM patients.

PMID- 20679736
TI  - Beneficial effects of adaptive servo ventilation in patients with chronic heart
      failure.
AB  - BACKGROUND: Sleep-disordered breathing (SDB) is thought to be a state of
      inflammation caused by hypoxic stress. Whether adaptive servo ventilation (ASV)
      attenuates the inflammatory response and improves the cardiac function of
      patients with congestive heart failure (CHF) accompanied by SDB was not been
      investigated. METHODS AND RESULTS: Seventeen inpatients with New York Heart
      Association (NYHA) II or III underwent polysomnography. There was a positive
      correlation between the apnea hypopnea index and high-sensitivity C-reactive
      protein (hs-CRP) level (r=0.753, P=0.016). The patients were divided into ASV
      (n=10) and non-ASV groups (n=7), and CHF-parameters were measured before and
      after ASV treatment. Improvement was noted for the NYHA class in the ASV group
      but not in the non-ASV group. In contrast to the non-ASV group, the level of
      brain natriuretic peptide (BNP), ejection fraction, and hs-CRP levels in the ASV
      group significantly improved (BNP, 212.1 +/- 181.2 to 77.3 +/- 54.0 pg/ml
      [P<0.05]; ejection fraction, 43.5 +/- 6.4 to 53.3 +/- 6.1% [P=0.002]; hs-CRP,
      0.85 +/- 0.58 to 0.21 +/- 0.19 mg/dl, [P=0.008]). The increase in ejection
      fraction was correlated with a decrease in the hs-CRP level (r=-0.753, P=0.001).
      CONCLUSIONS: Anti-inflammatory effects of ASV are important contributors for
      improving cardiac function in patients with CHF accompanied by SDB. 

PMID- 20679737
TI  - Comparison of plain balloon and cutting balloon angioplasty for the treatment of
      restenosis with drug-eluting stents vs bare metal stents.
AB  - BACKGROUND: The efficacy of cutting or plain balloon angioplasty (CBA or PBA) has
      not been analyzed for the treatment of drug-eluting stent (DES) restenosis vs
      bare metal stent (BMS) restenosis. METHODS AND RESULTS: The 252 in-stent
      restenosis (ISR) lesions in 224 consecutive patients treated by CBA (n=167) or
      PBA (n=85) between July 2002 and December 2007 were analyzed. At 6-month
      angiographic and 12-month clinical follow-up, CBA and PBA showed similar
      efficacies: repeat-ISR (37.0% vs 37.8%, P=0.90), late loss (0.62+/-0.60 vs 0.61+/
      0.47 mm, P=0.92), and target lesion revascularization (18.3% vs 22.4%, P=0.50).
      This comparable efficacy was maintained for treatment in the DES-ISR and BMS-ISR
      subgroups. However, target lesion-related myocardial infarction (n=9) occurred
      more frequently in the CBA than in the PBA arm (6.2% vs 0%, P=0.03), most of
      which developed early after ISR treatment (n=7; 54+/-26 days). Independent
      predictors of repeat-ISR were diffuse ISR and smaller pretreatment minimal lumen
      diameter, both of which might imply heavier plaque burden in the ISR group.
      CONCLUSIONS: Plain or cutting balloon angioplasty for ISR seems to be comparable,
      as the angiographic or clinical endpoints were not affected by initial stent type
      but by parameters related to the plaque burden of the ISR lesion. However, CBA
      might be associated with higher risk of myocardial infarction than PBA,
      suggesting more attention to dual-antiplatelet therapy after its use for ISR.

PMID- 20679738
TI  - Longitudinal changes in pulmonary function of asbestos workers.
AB  - OBJECTIVE: To observe the longitudinal changes in pulmonary function associated
      with exposure to asbestos in a group of highly exposed workers. METHODS:
      Pulmonary diffusing capacity (DLco) and spirometry of 243 Chinese asbestos
      workers were measured and remeasured after 5 and 10 yr. Their annual changes in
      relation to cumulative asbestos exposure and asbestosis were determined using
      multivariate analysis. RESULTS: The greatest annual decline was observed in DLco,
      particularly in workers with asbestosis, followed by FVC and FEV(1). A greater
      decline in DLco accorded with a higher level of cumulative asbestos exposure. A
      similar trend was also seen in FVC, in which the highest exposure level was
      associated with 223 ml loss over each 5 yr period or 45 ml/yr. CONCLUSIONS: There
      were substantial declines in DLco and FVC over time in the asbestos workers, and
      a dose-response trend between asbestos exposure and accelerating functional loss.

PMID- 20679739
TI  - Recent advances in the biology of heavy-ion cancer therapy.
AB  - Superb biological effectiveness and dose conformity represent a rationale for
      heavy-ion therapy, which has thus far achieved good cancer controllability while
      sparing critical normal organs. Immediately after irradiation, heavy ions produce
      dense ionization along their trajectories, cause irreparable clustered DNA
      damage, and alter cellular ultrastructure. These ions, as a consequence,
      inactivate cells more effectively with less cell-cycle and oxygen dependence than
      conventional photons. The modes of heavy ion-induced cell death/inactivation
      include apoptosis, necrosis, autophagy, premature senescence, accelerated
      differentiation, delayed reproductive death of progeny cells, and bystander cell
      death. This paper briefly reviews the current knowledge of the biological aspects
      of heavy-ion therapy, with emphasis on the authors' recent findings. The topics
      include (i) repair mechanisms of heavy ion-induced DNA damage, (ii) superior
      effects of heavy ions on radioresistant tumor cells (intratumor quiescent cell
      population, TP53-mutated and BCL2-overexpressing tumors), (iii) novel capacity of
      heavy ions in suppressing cancer metastasis and neoangiogenesis, and (iv)
      potential of heavy ions to induce secondary (especially breast) cancer.

PMID- 20679740
TI  - Recent innovations in carbon-ion radiotherapy.
AB  - In the last few years, hospital-based facilities for carbon-ion radiotherapy are
      being constructed and proposed in Europe and Asia. During the next few years,
      several new facilities will be opened for carbon-ion radiotherapy in the world.
      These facilities in operation or under construction are categorized in two types
      by the beam shaping method used. One is the passive beam shaping method that is
      mainly improved and systematized for routine clinical use at HIMAC, Japan. The
      other method is active beam shaping which is also known as beam scanning adopted
      at GSI/HIT, Germany. In this paper an overview of some technical aspects for beam
      shaping is reported. The technique of passive beam shaping is established for
      stable clinical application and has clinical result of over 4000 patients in
      HIMAC. In contrast, clinical experience of active beam shaping is about 400
      patients, and there is no clinical experience to respiratory moving target. A
      great advantage of the active beam shaping method is patient-specific collimator
      less and compensator-less treatment. This may be an interesting potential for
      adaptive radiotherapy.

PMID- 20679741
TI  - Radiation resistance in glioma cells determined by DNA damage repair activity of
      Ape1/Ref-1.
AB  - Since radiation therapy remains a primary treatment modality for gliomas, the
      radioresistance of glioma cells and targets to modify their radiation tolerance
      are of significant interest. Human apurinic endonuclease 1 (Ape1, Ref-1, APEX,
      HAP1, AP endo) is a multifunctional protein involved in base excision repair of
      DNA and a redox-dependent transcriptional co-activator. This study investigated
      whether there is a direct relationship between Ape1 and radioresistance in glioma
      cells, employing the human U87 and U251 cell lines. U87 is intrinsically more
      radioresistant than U251, which is partly attributable to more cycling U251 cells
      found in G2/M, the most radiosensitive cell stage, while more U87 cells are found
      in S and G1, the more radioresistant cell stages. But observed radioresistance is
      also related to Ape1 activity. U87 has higher levels of Ape1 than does U251, as
      assessed by Western blot and enzyme activity assays (approximately 1.5-2 fold
      higher in cycling cells, and approximately 10 fold higher at G2/M). A direct
      relationship was seen in cells transfected with CMV-Ape1 constructs; there was a
      dose-dependent relationship between increasing Ape1 overexpression and increasing
      radioresistance. Conversely, knock down by siRNA or by pharmacological down
      regulation of Ape1 resulted in decreased radioresistance. The inhibitors
      lucanthone and CRT004876 were employed, the former a thioxanthene previously
      under clinical evaluation as a radiosensitizer for brain tumors and the latter a
      more specific Ape1 inhibitor. These data suggest that Ape1 may be a useful target
      for modifying radiation tolerance.

PMID- 20679742
TI  - Proton beam dosimetry: a comparison between a plastic scintillator, ionization
      chamber and Faraday cup.
AB  - In this study, a comparison was made between a plastic scintillator (BC400), a
      Faraday Cup (FC) and an ionization chamber (IC) used for routine proton
      dosimetry. Thin scintillators can be applied to proton dosimetry and consequently
      to proton therapy as relative dosimeters because of their water-equivalent
      nature, high energy-light conversion efficiency, low dimensions and good
      proportionality to the absorbed dose at low stopping powers. To employ such
      scintillators as relative dosimeters in proton therapy, the corrective factors
      must be applied to correct the quenching luminescence at the Bragg peak. A fine
      linear proportionality between the luminescence light yield Y and the proton flux
      in a thin (0.5 mm) scintillator for the 20 and 30 MeV proton beams were observed.
      The experimental peak/plateau ratios of Bragg Curve for 2, 1 and 0.5 mm
      scintillators with an accuracy of 0.5% were obtained to be 1.87, 1.91 and 2.30,
      respectively. With combination of the Markus chamber and the CR-39 detector, the
      peak/plateau ratio was improved to 3.26. The obtained data of the luminescence
      yield as a function of the specific energy loss is in agreement with the Craun
      Birk's theory. Results show that the FC and Markus ionization chamber are in
      agreement within 4%, while the FC gives a lower dose evaluation. For a defined
      beam, the data for the fluence measurements are reproducible within a good
      accuracy.

PMID- 20679744
TI  - Lymph node retrieval after resection of rectal cancer following preoperative
      chemoradiotherapy.
AB  - BACKGROUND: According to the current guidelines of proper TNM staging, 12 lymph
      nodes per specimen are crucial. This study assessed the role of preoperative
      radiochemotherapy on the number of lymph nodes detected in the tumor-bearing
      specimen. MATERIAL AND METHODS: Retrospective data of 138 patients who underwent
      surgery for stage II and III rectal cancer without preoperative radiochemotherapy
      during the period of 2004-2006 (control group) were compared with prospective
      data of 38 patients who received preoperative radiochemotherapy during the period
      of 2007-2008 (study group). The number of patients with metastatic lymph nodes,
      number of lymph nodes per specimen, number of metastatic lymph nodes per
      specimen, and the size of the tumor between the groups were compared. RESULTS:
      Positive lymph nodes were detected in 88 (64%) patients in the control group as
      compared with 9 (21%) patients in the study group (P<0.05). The mean number of
      lymph nodes per specimen in the control group was 13.5, while in the study group,
      the mean number of lymph nodes per specimen was 6.29 (P<0.05). There was a
      significant difference in the mean number of metastatic lymph nodes per specimen
      between the groups (5.12 in the control group versus 2.11 in the study group;
      P<0.05). The mean size of the tumor was 4.37 cm in the control group and 2.45 cm
      in the study group (P<0.01). CONCLUSIONS: Preoperative radiochemotherapy for
      advanced rectal cancer significantly decreased the number of lymph nodes detected
      in the tumor-bearing specimen. This also resulted in a significant decrease in
      the number of metastatic lymph nodes detected in the specimen, and fewer patients
      with stage III (N+) cancer were diagnosed. Preoperative radiochemotherapy could
      induce a significant downsizing and downstaging of advanced rectal cancer, but
      great care in operative and pathologic examination techniques must be taken to
      ensure appropriate staging.

PMID- 20679743
TI  - Resveratrol attenuates radiation damage in Caenorhabditis elegans by preventing
      oxidative stress.
AB  - Resveratrol, a member of a class of polyphenolic compounds known as flavonols,
      has been extensively studied for its anticancer, antiviral, anti-inflammatory,
      and neuroprotective roles. Caenorhabidits elegans is a well-established animal
      for investigating responses to radiation. We found that resveratrol may provide
      protection against hazardous radiation. Pre-treatment with resveratrol extended
      both the maximum and mean life span of irradiated C. elegans. Resveratrol acted
      as a strong radical scavenger and regulated superoxide dismutase (SOD)
      expression. In addition, resveratrol was shown to be capable of alleviating gamma
      ray radiation exposure-induced reduction in mitochondrial SOD expression.
      Ultimately, a correlation may exist between dietary intake of trace amounts of
      resveratrol and anti-aging effects. A specific response mechanism may be
      activated after the administration of resveratrol in irradiated animals. Our
      results suggest the protective effect of resveratrol is due to its strong ability
      to protect from oxidative stress and protective effects in mitochondria.
      Therefore, resveratrol is potentially an effective protecting agent against
      irradiative damage.

PMID- 20679745
TI  - The value of clinical prognostic factors for survival in patients with invasive
      urinary bladder cancer.
AB  - The aim of the study was to evaluate the value of clinical prognostic factors for
      survival of patients with invasive urinary bladder cancer treated with radical
      cystectomy, chemotherapy, and radiotherapy. MATERIAL AND METHODS: A total of 115
      patients with invasive urinary bladder cancer were analyzed. Twenty-three
      patients with invasive urinary bladder cancer (pT2-T4) were treated according to
      the protocol of a prospective clinical study. In all the cases, transurethral
      resection was followed by radiation and chemotherapy. A total dose of 54-60 Gy of
      radiotherapy was delivered by daily fractions of 1.8-2.0 Gy each. Simultaneous
      chemotherapy was started on the same day as radiotherapy; gemcitabine at a dose
      of 175-300 mg/m(2) was delivered once a week intravenously for 6 weeks.
      Individual patient data was analyzed in a retrospective part of the study.
      Radical cystectomy was performed to 46 patients with invasive urinary bladder
      cancer, and radiotherapy was delivered to 46 patients. Inclusion criteria for
      patients into a prospective or retrospective trial were equal. We evaluated a
      prognostic value of various clinical factors for patients treated with radical
      cystectomy, chemoradiation with gemcitabine, and radiation alone. RESULTS: The 3
      year overall survival in the cystectomy group was 51.1%, in the chemoradiation
      group 38.0%, and in the radiotherapy group 26.9% (P=0.001). In univariate
      analysis in the chemoradiation group, completion of treatment according to the
      protocol showed a significant influence on overall survival (P=0.03). In the
      radiation group, completion of treatment according to the protocol showed a
      significant influence on overall survival too (P=0.01). In the radical cystectomy
      group, an important factor was a complete or incomplete TUR (P=0.02).
      Multivariate analysis showed a significance of hydronephrosis (P=0.03) and T
      stage (P=0.04) in the radiation therapy group. Comorbidity was found to be an
      independent prognostic factors in the chemoradiation group (P=0.02). CONCLUSIONS:
      The best 3-year overall survival was in the radical cystectomy group.
      Chemoradiation with gemcitabine could be offered as an alternative to patients
      refusing cystectomy. Better overall survival in the chemoradiation group was for
      patients without comorbidities and when treatment protocol was completed.

PMID- 20679746
TI  - The effect of induced sputum and bronchoalveolar lavage fluid from patients with
      chronic obstructive pulmonary disease on neutrophil migration in vitro.
AB  - OBJECTIVE: The aim of study was to investigate a chemotactic effect of induced
      sputum and bronchoalveolar lavage fluid on blood neutrophils in patients with
      chronic obstructive pulmonary disease (COPD) and healthy individuals. MATERIAL
      AND METHODS: Forty-three smokers with COPD, 19 ex-smokers with COPD, 13 healthy
      smokers, and 17 healthy nonsmokers were recruited to the study. Neutrophils were
      isolated from peripheral blood of study individuals. For the same experimental
      conditions, pooled induced sputum and bronchoalveolar lavage fluid of 20 COPD
      patients were used. Neutrophil chemotaxis in vitro was performed in cell
      transmigration chamber. Substances tested for chemoattraction (interleukin-8,
      induced sputum, bronchoalveolar lavage fluid directly or in addition to
      interleukin-8) were added to lower wells. Upper wells were filled with 2.5 x
      10(6)/mL of neutrophil culture and incubated for 2 hours. Migration was analyzed
      by flow cytometry. RESULTS: Interleukin-8 (10-100 ng/mL) induced a dose-dependant
      neutrophil migration in all the groups. Only 100 ng/L of interleukin-8 induced
      more intensive chemotaxis of neutrophils from COPD smokers as compared to ex
      smokers (P<0.05). Such difference between healthy individuals was obtained using
      30 ng/mL of interleukin-8 (P<0.05). Induced sputum/interleukin-8 (10-100 ng/mL),
      as well as induced sputum directly, induced neutrophil migration (P<0.05).
      Chemotaxis of neutrophils isolated from COPD patients and healthy nonsmokers did
      not depend on additional interleukin-8 concentration. Bronchoalveolar lavage
      fluid/interleukin-8 (30-100 ng/mL) induced more intensive migration of
      neutrophils from COPD patients than bronchoalveolar lavage fluid (P<0.05) alone.
      CONCLUSIONS: Migration of neutrophils isolated from patients with COPD was more
      intensive compared to healthy individuals. Induced sputum and bronchoalveolar
      lavage fluid directly and with addition of interleukin-8 stimulated chemotaxis,
      and it was higher in neutrophils from COPD patients. Migration of neutrophils did
      not depend on smoking status.

PMID- 20679747
TI  - Surgical treatment of metastatic tumors of the femur.
AB  - OBJECTIVE: To evaluate the patients functional outcome and pain control after
      resection of metastatic femoral tumors. MATERIAL AND METHODS: A prospective
      randomized clinical study was conducted, which included 26 cases of metastatic
      tumors of the femur with an associated pathologic fracture. These selected cases
      were randomly divided into two groups based upon the using of methylmethacrylate
      cement in fracture fixation. Group 1 (n=13) included all cases where the
      fractures were treated with bone cement augmentation. Group 2 (n=13) included all
      cases where the fractures were treated without bone cement augmentation.
      Functional outcome was evaluated according the American Musculoskeletal Tumor
      Society system. RESULTS: Good and excellent pain control was achieved in 61.5%,
      satisfactory in 38.5% of all cases in the Group 1 versus 15.5% (P=0.015) and 69%
      (chi(2)=2.4762; P=0.115) of all cases in the Group 2. Functional outcome after
      femoral metastasis resection and pathologic fracture fixation was significantly
      better in the Group 1. Total lower extremity function of full normal function was
      67% in the Group 1 versus 49% in the Group 2 (P<0.05). We did not observe
      significant difference between patients' postoperative survival in the groups
      (P>0.05). The postoperative durability of stable pathologic fracture fixation was
      shorter in the Group 2 (273.9+/-51.7 vs. 358.9+/-116.8 days) comparing with Group
      1 (P=0.03). CONCLUSIONS: The introduction of bone cement as the adjunct to the
      pathologic femoral fracture fixation significantly improved the clinical our
      study results: we achieved better functional outcome and better pain control.

PMID- 20679748
TI  - Comparative diagnostic value of contrast-enhanced ultrasonography, computed
      tomography, and magnetic resonance imaging in diagnosis of hepatic hemangiomas.
AB  - AIM: To compare the value of intravenous contrast-enhanced ultrasonography (US),
      intravenous contrast-enhanced computed tomography (CT), and magnetic resonance
      imaging (MRI) in the diagnosis of hepatic hemangiomas. MATERIAL AND METHODS: The
      study enrolled 48 patients, aged between 20 and 79 years (35 [72.9%] women, 13
      [27.1%] men; mean age, 53.5+/-12.855 years), who were examined and treated in the
      Departments of Gastroenterology, Surgery, and Oncology, Hospital of Kaunas
      University of Medicine, in the year 2007. All patients underwent intravenous
      contrast-enhanced US, intravenous contrast-enhanced CT, and MRI and were
      diagnosed with hepatic hemangioma according to the findings of these
      examinations. RESULTS: The size of hemangiomas was < or =2.0 cm in 20 cases
      (41.7%) and >2.0 cm in 28 (58.3%). No association between hepatic hemangioma and
      patient's age was found (chi(2)=0.547, df=2, P=0.761). Nearly one-third of
      hemangiomas were located in the segment IV of the left hepatic lobe. There were a
      few complicated hemangiomas in the study sample: 2 with calcification and 1 with
      necrosis. The sensitivity of CT in the diagnosis of hepatic hemangioma was
      76.92%; specificity, 33.3%; positive prognostic value, 83.3%; and negative
      prognostic value, 25.0%. The sensitivity of intravenous contrast-enhanced US in
      the diagnosis of hepatic hemangioma was 77.8%; specificity, 100%; positive
      prognostic value, 100%; and negative prognostic value, 23.1%. CONCLUSIONS:
      Intravenous contrast-enhanced US is more specific than intravenous contrast
      enhanced CT in the diagnosis of hepatic hemangioma (P=0.0005) and has a higher
      positive prognostic value (P=0.001).

PMID- 20679749
TI  - [Resistance of the main bronchial stump to pressure after manual suture].
AB  - OBJECTIVE: To study the resistance of manual sutures used for the closure of the
      main bronchial stump to intraluminal inflation pressure. MATERIAL AND METHODS: A
      total of 16 human intact cadaveric tracheobronchial tree specimens were selected
      in the Department of Pathology. All specimens were dissected so that the intact
      trachea and main bronchi remained en bloc without perforation. Then they were
      randomized into either group A or B. Both groups consisted of 16 specimens: 8
      right main bronchi and 8 left main bronchi. In the group A, the bronchial stump
      was closed with typical manual running suture using 3/0 Vicryl. In the group B,
      the bronchial stump was closed with modified manual running suture using 3/0
      Vicryl. The trachea in all cases was intubated with a standard endotracheal tube
      followed by inflation of the cuff. The proximal end of the tube was connected to
      a sphygmomanometer. The specimens were submerged in water, and intraluminal
      pressure monitored by the mercury column gradually increased until air leakage
      was observed. RESULTS: The median leakage pressure was significantly higher in
      the group B as compared to the group A (142+/-14.2 versus 106.6+/-11.2 mm Hg,
      P<0.001). In the group A, the weakest site of the suture was revealed.
      CONCLUSIONS: Modified manual running sutures of the main bronchial stump revealed
      a significantly higher resistance to intraluminal inflation pressure as compared
      with typical manual running sutures. It may contribute to better early
      postoperative tolerance to abnormal pressure before sound healing of the main
      bronchial stump is achieved.

PMID- 20679750
TI  - Gliomatosis cerebri.
AB  - Gliomatosis cerebri is a rare diffusely infiltrating glial tumor involving two or
      more lobes and is frequently is bilateral. Infiltrative extent of tumor is out of
      proportion to histological and clinical features. We present a case in which
      finally the diagnosis of gliomatosis cerebri was made. In this case, computed
      tomography showed that midline structures were insignificantly shifted to the
      left, there was a mild dilatation of lateral ventricles more expressed on the
      right, and no pathologic changes of brain tissue density were found. On magnetic
      resonance tomography, T2W/SE and T2W/FLAIR images revealed zones of hyperintense
      signal, spreading with time, through several lobes of the brain with no
      enhancement on T1W images. Diagnosis of gliomatosis cerebri was suspected,
      stereotaxic biopsy was performed, and pathological examination revealed changes
      typical of diffuse glial tumor. In this article, changes typical of gliomatosis
      cerebri seen in other radiological methods such as computed tomography, magnetic
      resonance spectroscopy, dynamic contrast-enhanced T2*-weighted magnetic
      resonance, and positron emission tomography also are discussed.

PMID- 20679751
TI  - mTHPC-mediated photodynamic treatment of Lewis lung carcinoma in vitro and in
      vivo.
AB  - BACKGROUND AND OBJECTIVE: The ongoing search for the enhancement of efficacy of
      photodynamic therapy stimulates the interest in molecular mechanisms of the
      response to the treatment. Looking for the cell line suitable for investigation
      of cellular response both in vivo and in vitro, we evaluated phototoxicity of m
      tetrakis-(3-hydroxyphenyl)-chlorin (mTHPC) on viability of Lewis lung carcinoma
      (LLC1) cells in vitro, growth of murine transplantable tumor, and mice survival.
      MATERIAL AND METHODS: LLC1 cell culture and male C57BL/6 mice bearing Lewis lung
      carcinoma were used for the experiments. Photodynamic treatment was mediated by m
      tetrakis-(3-hydroxyphenyl)-chlorin as a photosensitizer. Light emitting diode
      array was used for illumination. The effect of the photodynamic treatment was
      evaluated by comparison of viability of control and treated cells, growth of
      tumors, and survival of the control and treated mice. RESULTS: In vitro, a
      cytotoxic dose inducing a reduction in viability of LLC1 cells by 50% was
      achieved at 60 mJ/cm(2) and approximately 400 ng/mL of the photosensitizer, or 30
      mJ/cm(2) and 600 ng/mL of mTHPC. Both the concentration of the photosensitizer
      and duration of light exposure were significant determinants of cytotoxic effect.
      In vivo, an injection of 0.25 mg/kg of mTHPC to mice bearing Lewis lung tumor and
      illumination at 120 J/cm(2) taking place after 24 h significantly inhibited tumor
      growth and prolonged mice survival. However, the tumors regained their growth
      potential after 9 days. CONCLUSIONS: Photodynamic treatment mediated by m
      tetrakis-(3-hydroxyphenyl)-chlorin had a significant effect on LLC1 cells in
      vitro and growth of Lewis lung carcinoma in vivo.

PMID- 20679752
TI  - Evaluation of health-related quality of life in patients with breast cancer.
AB  - BACKGROUND: Breast cancer is the most common cancer among women, comprising about
      23% of all cancer types. About 1300 new cases of breast cancer are registered in
      Lithuania annually. During the last decade, health-related quality of life has
      become an important part of breast cancer treatment. Pain, fatigue, and sleep
      disorders are important aspects of health-related quality of life. The aim of the
      study was to evaluate health-related quality of life (HRQL) among patients with
      breast cancer in Lithuania. The main tasks were to analyze HRQL in
      sociodemographic and clinical aspects, and to determine symptoms that have the
      greatest impact on HRQL . MATERIAL AND METHODS: A cross-sectional study was
      carried out in four major Lithuanian hospitals. An EORTC QLQ-C30 (version 3)
      questionnaire with general demographic and medical information was distributed
      among 318 patients. A total of 284 patients were included in the analysis.
      RESULTS: The response rate was 89%. The mean age of patients was 55.9 years (SD,
      10.1 years), and the mean time from diagnosis--2.36 years (SD, 3.2 years). A
      greater part (65%) of the studied women lived in a family or with a partner.
      Women reported high level of functioning across several standardized HRQOL
      scales: cognitive functioning, everyday activity, and physical functioning.
      Fatigue and sleeping disorders were the most commonly indicated symptoms in the
      symptom scale. Fatigue and pain were the most important factors affecting general
      HRQOL. CONCLUSIONS: Our results emphasize that the general HRQOL of the studied
      women is fair, but poorer than that of the corresponding population in other
      countries. Women living in a family or partnership experienced fewer financial
      troubles and had higher HRQOL scores across several standardized measures
      compared to those who were single. Women with late stages of breast cancer felt
      worse and were less socially active compared to women who were diagnosed with
      early-stage breast cancer.

PMID- 20679753
TI  - [Acute glomerulonephritis associated with Mycoplasma pneumonia].
AB  - A rare case of acute glomerulonephritis associated with Mycoplasma pneumoniae
      pneumonia is described. Although various types of renal damage associated with
      Mycoplasma infection have been reported in medical literature, kidney disease
      resembled classical postinfectious glomerulonephritis in this case. Possibly, the
      only difference was that the first signs of kidney disease almost coincided with
      symptoms of respiratory tract infection, instead of appearing at least a week
      later. The clinical course and outcome of the kidney disease were favorable.

PMID- 20679754
TI  - Flapless surgery and immediately loaded implants: a retrospective comparison
      between implantation with and without computer-assisted planned surgical stent.
AB  - OBJECTIVES: Computer planned flapless surgery and immediate loading are the most
      recent topics in implantology. One new computer-planned implant system uses a
      three-dimensional parallelometer able to transfer the implant position from the
      virtual project to the master model. The aim of this study was to verify if the
      new medical device gives an advantage in term of implant failures and/or crestal
      bone remodeling. MATERIAL AND METHODS: A retrospective study was planned to
      analyze a series of 193 immediately loaded fixtures inserted by means of flapless
      surgery. From those sixty six implants were inserted with computer planning
      whereas 127 were inserted "free-hand". Several variables related to patient,
      anatomy, implant, surgery and prosthesis were investigated. To detect the
      clinical outcome implant' failure and peri-implant bone resorption were
      considered. Kaplan-Meier algorithm and Cox regression were then performed to
      detect those variables statistically associated with the clinical outcome.
      RESULTS: Implant length and diameter ranged from 10 to 16 mm and from 3.75 to 6.0
      mm, respectively. Implants were inserted to replace 46 incisors, 30 cuspids, 75
      premolars and 42 molars. The mean follow-up period was 15 months. Seven implants
      were lost (survival rate 96.4%) but no studied variable has a statistical impact
      on failures. On the contrary, implants inserted in sites with completed bone
      healing, wide diameter fixtures and implants inserted in totally edentulous jaw
      had a significantly lower crestal bone resorption. The other variables (age,
      gender, upper/lower jaws, tooth site, implant' type and length, number of
      prosthetic units antagonist condition) did not have impact on crestal remodeling.
      CONCLUSION: Computer-planned and cast model transferred implantology is a
      reliable technology that provides a slightly higher clinical outcome than "free
      hand" technique at least in healed sites, wider implants and totally edentulous
      jaws.

PMID- 20679755
TI  - Technical aspects of endodontic treatment procedures among Lithuanian general
      dental practitioners.
AB  - OBJECTIVE: The purpose of this study was to gather information about the various
      aspects, technical and biological, of endodontic treatment as performed by
      Lithuanian general dental practitioners and to compare their choices with
      established endodontic treatment standards of undergraduate education. MATERIALS
      AND METHODS: Questionnaires were sent to all 2,850 Lithuanian dental
      practitioners. The structured questionnaire included inquiries about gender,
      duration of professional activity, working environment, details about instruments
      and materials. RESULTS: From total 1532 (53.8%) questionnaires were returned.
      Only responses from general dental practitioners (1431) were included. Of the
      respondents 66% never used a rubber dam. Most practitioners relied on
      conventional stainless steel instruments. The NiTi hand files were often and
      routinely used by 32.2% of the respondents. Sodium hypochlorite was the most
      popular choice as a root canal irrigant. Calcium hydroxide paste was used as an
      inter-appointment medicament. Cold-lateral condensation root filling method was
      used by 72.8% of the respondents while 15.6% used a paste for the root filling.
      CONCLUSIONS: The results of this study indicate that the recently graduated
      dental practitioners were following the recommended standard of endodontic
      treatment better than those with a longer time from the graduation. It is
      important to improve the quality of existing courses of continuous education in
      endodontology in order to ensure the necessary competency in clinical practice.
      The low use of a rubber dam and low adoption of new technologies in Lithuania is
      not acceptable and needs to be changed.

PMID- 20679756
TI  - Electromyographic and cephalometric correlation with the predominant masticatory
      movement.
AB  - OBJECTIVE: This study aimed to evaluate the chewing muscular dynamics and
      correlate the side of the masticatory movement that is more vertical and/or more
      horizontal established by the photomeasurement Masticatory Functional Angle (MFA)
      to the muscular activity behavior, showed in the surface electromyography and in
      the radiographic images. MATERIAL AND METHOD: Seventeen people were selected of
      both genders, with the average age of 25 years, without signs or apparent
      symptoms of masticatory muscular disorders. The teleradiographies were done in
      lateral norm and surface electromyography of the masseter muscles, anterior
      portion of temporal and supra-hyoids in rest position and maximal bite. The bite
      force measured with a metallic transducer that was connected to a force sensor
      (Strain Gauge) to measure the deformation of the material model SF4 (EMG SYSTEM
      DO BRASIL). A mandibular goniometer of the EMG System of Brazil was used to
      measure the opening size. RESULTS: The comparison and correlation were
      established between the groups with MFA>5 degrees and MFA<5 degrees by the test
      "t" of Student or test of Mann-Whitney conform the distribution was normal or
      not, respectively. The results showed significant differences between groups,
      although without sexual dimorphism, to masseter muscle in maximal bite.
      CONCLUSION: In conclusion, the anatomic-physiological aspects of
      temporomandibular disorders are related to the asymmetrical mandible function.

PMID- 20679757
TI  - The impact of salivary mutans streptococci and sugar consumption on caries
      experience in 6-year olds and 12-year olds in Riga.
AB  - OBJECTIVE: To assess possible relationship between caries experience, salivary
      cariogenic microflora and free sugar consumption in 6 year and 12 year old
      children in Riga, to evaluate these variables in risk assessment. MATERIALS AND
      METHODS: 79 children aged 6 and 96 children aged 12 were examined clinically and
      by bitewing X-ray for caries diagnosis. Also all children or their parents were
      questioned about number of tea spoons containing sugar used per cup and frequency
      of cups used daily. Salivary mutans streptococci (MS) and lactobacilli (LB) (CRT
      bacteria; Ivoclar; Vivadent; Liechtenstein) were determined only for children
      with dmft/DMFT>4: 27.8% at the age of 6, 40.6% at the age of 12. All data were
      statistically analyzed using frequency tables and analysis of variance.
      Statistical significance of differences in proportions was tested using chi
      square test, Analysis included evaluation of how changes in variables such as
      free sugar consumption affects caries in particular age group. RESULTS: Mean
      number of tea spoons containing sugar used per cup was 1.47 in 6 year olds and
      1.86 in 12 year olds, but daily amount of tea spoons containing sugar was 2.71
      and 4.36 in each age group accordingly. Tea spoons of sugar per cup were
      associated with caries experience only in 6 year olds (p=0.098). A significant
      association was observed between caries experience, salivary MS and an amount of
      tea spoons containing sugar used per cup in both age groups (for 6 y.o. p= 0.037,
      for 12 y.o. p=0.037). Also caries experience was strongly associated with
      salivary MS and daily amount of tea spoons containing sugar, but only in 12 year
      olds (p=0.041). CONCLUSIONS: The information of free sugar consumption per cup or
      daily gives the possibility to control free sugar use in order to reduce caries
      development in 6 year old and 12 year old children in Riga.

PMID- 20679758
TI  - Changes in oral health-related quality of life among children following dental
      treatment under general anaesthesia. A systematic review.
AB  - AIM: To review the results of studies reporting data on changes in aspects of
      children's oral-health-related quality of life (OHRQoL) following dental
      treatment under general anaesthesia (GA). To describe instruments measuring
      children's OHRQoL used in the studies. METHODS: A literature review was carried
      out to identify relevant studies reporting data on changes in aspects of
      children's OHRQoL following dental treatment under GA. The data was extracted
      from the selected papers. RESULTS: The review included 11 journal articles, which
      presented the results of clinical trials. The studies were based on different
      questionnaires measuring children's OHRQoL and parental satisfaction.
      CONCLUSIONS: Oral rehabilitation under GA results in the immediate improvement of
      children's oral health and physical, emotional and social quality of life. It
      also has a positive impact on the family. However, a more accurate comparison of
      results is not possible due to differences in instruments used. And no single
      decision exists on the choice of the instrument measuring children's OHRQoL
      following dental treatment under GA. It may be concluded that further studies on
      measuring long term OHRQoL changes and studies surveying children are needed.

PMID- 20679760
TI  - Acute hepatitis B virus infection despite previous immunization in the context of
      recent HIV-1 infection.

PMID- 20679759
TI  - Periconception pre-exposure prophylaxis to prevent HIV transmission: benefits,
      risks, and challenges to implementation.
AB  - HIV-serodiscordant couples face complicated choices between fulfilling
      reproductive desire and risking HIV transmission to their partners and children.
      Sexual HIV transmission can be dramatically reduced through artificial
      insemination and sperm washing; however, most couples cannot access these
      resources. We propose that periconception pre-exposure prophylaxis (PrEP) could
      offer an important, complementary therapy to harm reduction counseling programs
      that aim to decrease HIV transmission for couples who choose to conceive. In this
      paper, we describe the potential benefits of periconception PrEP and define
      critical points of clarification prior to implementation of PrEP as part of a
      reproductive health program. We consider sexual transmission risk, current risk
      reduction options, PrEP efficacy, cost, adherence, resistance, fetal toxicity,
      and impact of PrEP counseling on entry into health services. We address PrEP in
      the context of other periconception HIV-prevention strategies, including
      antiretroviral treatment of the HIV-infected partner. We conclude that, should
      PrEP prove safe and efficacious in ongoing trials, periconception PrEP may offer
      a useful approach to minimize risk of HIV transmission for individuals of
      reproductive age in HIV-endemic countries.

PMID- 20679761
TI  - First report of abacavir associated with hypoglycemia.

PMID- 20679762
TI  - Concurrency and the limited effectiveness of behavioural interventions on sexual
      risk behaviour of youth in sub-Saharan Africa.

PMID- 20679763
TI  - AIDS education programs miss target.

PMID- 20679764
TI  - Pandemic influenza vaccine in adult HIV-1-infected patients.

PMID- 20679767
TI  - Current world literature.

PMID- 20679766
TI  - Primary prevention of heart failure: an update.
AB  - PURPOSE OF REVIEW: The prevalence of heart failure is increasing world-wide.
      Primary prevention is essential. There are no trials targeting primary
      prevention. This review will focus on recently published studies that support
      drug therapy and lifestyle modification of high risk patients. RECENT FINDINGS:
      Recent meta-analyses confirm the beneficial effect of ACE-inhibitors, angiotensin
      receptor blockers, and diuretics and/or beta blockers in the prevention of heart
      failure. However, heart failure is increased in patients receiving calcium
      channel blockers when compared with those receiving ACE-Is and beta blockers.
      High adherence to antihypertensive therapy results in a significant reduction in
      heart failure. Targeting a systolic blood pressure of less than 120 mmHg compared
      with less than 140 mmHg in diabetic hypertensive patients does not appear to
      decrease the development of heart failure. Not smoking, maintaining a healthy
      weight, performing regular exercise, and maintaining a healthy diet decrease the
      incidence of heart failure. SUMMARY: Utilization of antihypertensive agents
      appears to be the best global strategy for the prevention of heart failure. ACE
      inhibitors and angiotensin-receptor blockers remain excellent first line agents.
      A large proportion of heart failure risk is due to modifiable factors, which need
      to be identified and controlled. Smoking confers up to a two-fold risk for the
      development of heart failure in the elderly and should be aggressively targeted.

PMID- 20679769
TI  - Mantle cell lymphoma in relapse: the role of emerging new drugs.
AB  - PURPOSE OF REVIEW: Despite current advances in the therapy for newly diagnosed
      mantle cell lymphoma (MCL), relapsed MCL continues to have a poor prognosis.
      Advances in our understanding of the molecular pathogenesis of MCL are yielding
      many promising novel therapies. RECENT FINDINGS: This article reviews the unique
      biology of MCL and describes how our understanding of its cell cycle
      dysregulation, and impaired apoptotic pathways is yielding many potential
      therapeutic targets including cyclin D1 and the cell cycle regulatory proteins,
      inhibitors of mammalian target of rapamycin, the proteasome, and proapoptotic
      family members. Recent preclinical and clinical data with cdk inhibitors, histone
      deacetylase inhibitors, the proteasome inhibitor bortezomib, mammalian target of
      rapamycin inhibitors, and other experimental strategies such as immunotherapy and
      microRNA are discussed. SUMMARY: Understanding these targeted therapies in the
      context of the biology of MCL, has the potential to develop novel therapeutic
      platforms for the treatment of relapsed MCL, and will hopefully change the
      outcome for patients with this challenging clinical condition.

PMID- 20679770
TI  - Implications of the tumor microenvironment on survival and disease response in
      follicular lymphoma.
AB  - PURPOSE OF REVIEW: Although outcomes for patients with follicular lymphoma have
      improved with chemoimmunotherapy, the disease remains incurable. There is a wide
      variation in survival, and although the Follicular Lymphoma International
      Prognostic Index helps to risk-stratify patients, there is a need for robust
      biomarkers of disease outcome. Most patients will succumb to the emergence of
      chemoresistance or transformation to diffuse large B-cell lymphoma and there is a
      need for new treatment approaches in this disease. RECENT FINDINGS: Gene
      expression profiling studies and immunohistochemical analyses have highlighted
      the importance of the tumor microenvironment in follicular lymphoma. There have,
      however, been conflicting results regarding the prognostic significance of
      specific subsets of immune cells in follicular lymphoma. Recent studies have
      highlighted the interaction of specific treatment protocols and the immune
      environment on outcome. We are now beginning to uncover the molecular basis of
      the complex interactions that occur between follicular lymphoma cells and the
      immune microenvironment. SUMMARY: There is an active interaction between
      follicular cells and the microenvironment that determines the clinical behavior,
      prognosis, and response to specific treatment protocols. As we have a more
      complete understanding of this complex interaction it is the likely that the
      tumor microenvironment itself may become a target of therapy, or that therapy
      might be tailored based upon the specific immune microenvironment of the biopsy.

PMID- 20679771
TI  - Current world literature.

PMID- 20679773
TI  - Current world literature.

PMID- 20679774
TI  - Deep anaesthesia reduces postoperative analgesic requirements after major
      urological procedures.
AB  - BACKGROUND AND OBJECTIVE: There is evidence from previous studies that deeper
      anaesthetic levels reduce postoperative pain along with analgesic requirements.
      The aim of this study was to confirm this observation during major urological
      procedures under sevoflurane anaesthesia. METHODS: Seventy ASA I or II patients
      undergoing radical prostatectomy or nephrectomy were randomly allocated into two
      groups: the L-BIS group with BIS (bispectral index scale) values kept within a
      range of 20-30 and the H-BIS group with values within the range of 50-60.
      Sevoflurane was the main anaesthetic agent used, along with inhalation of nitrous
      oxide and continuous remifentanil infusion. Postoperative analgesia was achieved
      mainly through morphine and ketamine, which was continuously infused by pump, and
      intravenous parecoxib. Additional analgesics (paracetamol, parecoxib and
      morphine) were administered in persistent (continuous, lasting longer than
      predicted and requiring repeated doses of analgesics) postoperative pain. The
      number of patients who demanded additional analgesia during the first 24 h was
      recorded, as well as the number of administrations performed, along with visual
      analogue scale (VAS) scores at 8 and 24 h. RESULTS: Sixty patients completed the
      study, 30 in each group. VAS scores at 8 h were significantly higher in the H-BIS
      group, both at rest [1 (0-4) vs. 2 (0-8), P = 0.036] and on cough [1 (0-5) vs. 2
      (2-9), P = 0.021], but at 24 h were similar between the two groups. Four patients
      in the L-BIS group and 17 patients in the H-BIS group demanded additional
      analgesia (P < 0.0009), although the patients in the L-BIS group needed
      significantly fewer additional doses of analgesics than those in the H-BIS group
      [0 (0-2) vs. 1 (0-5), P < 0.0008]. CONCLUSION: The results show that
      intraoperative deep anaesthetic levels during major urological procedures,
      achieved with high sevoflurane concentrations, lead to reduced postoperative
      analgesic requirements.

PMID- 20679775
TI  - Inadvertent administration of drug residue causing respiratory arrest: case
      series.

PMID- 20679776
TI  - Never stop learning.

PMID- 20679777
TI  - Evidence-based practices of gastroenterology nurses.
AB  - Evidence-based practice (EBP) incorporates use of the best scientific knowledge,
      expert opinion, clinician experience, and patient preferences to facilitate the
      best patient outcomes in healthcare. Recent studies have suggested that nurses
      lack the skills and expertise to facilitate EBP in a meaningful way. This
      replication study (n = 225) investigated the EBPs of gastroenterology nurses in
      the United States. Findings generally support the previous studies that suggest
      nurses do not yet possess the skills or resources to implement EBP.
      Recommendations for addressing this deficit in the specialty of gastroenterology
      nursing are discussed.

PMID- 20679778
TI  - Summary of the causative and treatment factors of diarrhea and the use of a
      diarrhea assessment and treatment tool to improve patient outcomes.
AB  - This article is a review of the causative factors and pharmacologic treatments of
      diarrhea. This information was incorporated into a Diarrhea Assessment and
      Treatment Tool (DATT) to guide clinicians on comprehensive diarrhea assessment
      and current treatment recommendations. The tool was utilized at a university
      affiliated oncology institution by a clinical nurse specialist on 26 patients as
      a performance improvement project. Ease of use and efficacy of DATT were tested.
      Eighty-one percent of patients were assessed using DATT in 30 minutes or less.
      Seventy-nine percent of the 57 identified diarrhea classifications were not being
      treated upon initial assessment. Diarrhea control was achieved in 73% of the
      patients within 7 days or fewer when DATT was utilized. The premise of diarrhea
      management is that if all the causative factors are not treated, diarrhea will
      persist. The conclusions are that this tool will aid the clinician in a
      comprehensive assessment of diarrhea and provide a systematic approach to
      diarrhea treatment. The need for research on best practice for management of the
      various causative factors of diarrhea is needed.

PMID- 20679780
TI  - Review of propofol and auxiliary medications used for sedation.
AB  - The sedative-hypnotic propofol (2,6-diisopropylphenol) is being increasingly used
      for sedation during painful diagnostic and therapeutic procedures in adults and
      children. The purpose of this article is to present a general overview of the use
      of propofol for endoscopic sedation. Advantages and disadvantages of using
      propofol for sedation, as well as its pharmacokinetics, preparation for use,
      dosing for endoscopic sedation, auxiliary sedative and analgesic medication
      options, methods of administering, adverse effects with interventions, recovery,
      and patient-physician satisfaction are discussed. Finally, next steps necessary
      to optimize future use of propofol are suggested.

PMID- 20679782
TI  - A retrospective analysis comparing small bowel follow-through with wireless
      capsule endoscopy in the evaluation of obscure gastrointestinal bleeding.
AB  - A comparative retrospective study was conducted to evaluate diagnostic findings
      between small bowel follow-through (SBFT) and wireless capsule endoscopy in the
      presence of obscure gastrointestinal bleeding. A convenience sample of 31
      patients with previous negative upper and lower endoscopy was included in the
      study. Wireless capsule endoscopy established a significant source of obscure
      gastrointestinal bleeding 53% of the time. The diagnostic capacity of
      radiographic SBFT was measured at 17% as compared with that of the wireless
      capsule endoscopy. The clinical findings along with the digital images obtained
      from the wireless capsule endoscopy was found to be the optimum diagnostic tool
      in the evaluation of obscure gastrointestinal bleeding in the small bowel.

PMID- 20679783
TI  - Endoscope reprocessing methods: a prospective study on the impact of human
      factors and automation.
AB  - The main cause of endoscopy-associated infections is failure to adhere to
      reprocessing guidelines. More information about factors impacting compliance is
      needed to support the development of effective interventions. The purpose of this
      multisite, observational study was to evaluate reprocessing practices, employee
      perceptions, and occupational health issues. Data were collected utilizing
      interviews, surveys, and direct observation. Written reprocessing policies and
      procedures were in place at all five sites, and employees affirmed the importance
      of most recommended steps. Nevertheless, observers documented guideline
      adherence, with only 1.4% of endoscopes reprocessed using manual cleaning methods
      with automated high-level disinfection versus 75.4% of those reprocessed using an
      automated endoscope cleaner and reprocessor. The majority reported health
      problems (i.e., pain, decreased flexibility, numbness, or tingling). Physical
      discomfort was associated with time spent reprocessing (p = .041). Discomfort
      diminished after installation of automated endoscope cleaners and reprocessors (p
      = .001). Enhanced training and accountability, combined with increased
      automation, may ensure guideline adherence and patient safety while improving
      employee satisfaction and health.

PMID- 20679785
TI  - Nominations for national gastroenterology nursing awards.

PMID- 20679784
TI  - Repeating gastric biopsy for accuracy of gastric lymphoma diagnosis.
AB  - Gastric lymphoma is characterized by a good prognosis with slow progression and a
      nonspecific appearance under the endoscope. A biopsy is performed for accurate
      diagnosis. For this study, endoscopy and biopsy specimens were analyzed
      retrospectively to investigate the rate of accurate diagnosis of gastric lymphoma
      in first-, second-, and third-round endoscopic and biopsy procedures and to
      understand the causes of discrepancies. Fifty-four cases of gastric lymphoma were
      diagnosed in 32,000 patients. The rate of positive Helicobacter pylori infection
      was 70.4%. Of these, 13 cases were diffuse large B-cell lymphoma and 41 cases
      were marginal zone B-cell lymphoma. Thirty-two gastric lymphoma cases (59.3%)
      were diagnosed by first-round endoscopy and biopsy, 13 (24.1%) cases required
      second-round endoscopy and biopsy, and 9 (16.7%) cases were determined in the
      third round of endoscopic and biopsy procedures. Repeating endoscopy and biopsy
      reduced discrepancies in the diagnosis of gastric lymphoma by 40.8%, which can
      significantly improve the overall accuracy of diagnosis and treatment of gastric
      lymphoma.

PMID- 20679786
TI  - Midwest Benchmarking Group: help is out there.

PMID- 20679787
TI  - Hallmarks of conscious sedation.

PMID- 20679788
TI  - Vascular anomalies and lymphedema.
AB  - LEARNING OBJECTIVES: After studying this article, the participant should be able
      to: 1. Define the difference between vascular tumors and malformations. 2.
      Distinguish between the natural history of hemangiomas and that of vascular
      malformations. 3. Identify the different types of hemangiomas and vascular
      malformations and understand evaluation, treatment, and complications. 4.
      Understand the role of lymphaticovenular anastomoses in the treatment of
      extremity lymphedema. BACKGROUND: The International Society for the Study of
      Vascular Anomalies classification, which is the most widely accepted
      classification system in use, divides vascular anomalies into vascular tumors
      (inclusive of hemangiomas) and malformations. This serves as a guideline for
      diagnosis, evaluation, and treatment of these lesions. METHODS: Although
      hemangiomas tend to have a predictable clinical course over the first year of
      life, going through proliferating, involuting, and involuted stages, vascular
      malformations demonstrate growth commensurate with age, often becoming more
      prominent in puberty. In addition, they never regress, and persist throughout
      life. RESULTS: Different modalities of treatment may be appropriate for vascular
      tumors and different subsets of vascular malformations. Details are provided in
      this review. Lymphaticovenular anastomoses provide an excellent addition to our
      methods of treatment of extremity lymphedema, and are made possible through
      development of supermicrosurgical techniques. CONCLUSIONS: Vascular anomalies
      have a high prevalence in the general population. Thus, it is vital that the
      plastic surgeon has a good understanding of classification, evaluation, and
      treatment options. Lymphedema is another common condition that is encountered.
      Understanding of lymphaticovenular anastomoses and their applications aids
      treatment planning for select patients.

PMID- 20679789
TI  - Craniobank: an online collection of three-dimensional normative craniofacial
      images.

PMID- 20679790
TI  - The quilting suture: its application in face lifts.

PMID- 20679791
TI  - Recycling the dorsal hump: a simple technique to prevent dorsal irregularities in
      primary rhinoplasty.

PMID- 20679792
TI  - Successful microsurgical replantation of the amputated nose.

PMID- 20679793
TI  - Hyaluronic Acid dermal filler for the treatment of oral incompetence.

PMID- 20679794
TI  - Trigonometric calculation of implant depth.

PMID- 20679795
TI  - Platysma chemical denervation with botox before neck lift.

PMID- 20679796
TI  - Feasibility of bionic reanimation of a paralyzed face: a preliminary study of
      functional electrical stimulation of a paralyzed facial muscle controlled with
      the electromyography of the contralateral healthy hemiface.

PMID- 20679797
TI  - Proving the effectiveness of the lip lift for treatment of the aging lip: a
      morphometric evaluation.

PMID- 20679798
TI  - Usefulness of skin trephine in minimally invasive cancellous bone harvesting for
      secondary alveolar bone grafting in young patients.

PMID- 20679799
TI  - The type 4 DIEA: A newly identified branching pattern of the deep inferior
      epigastric artery.

PMID- 20679800
TI  - Improving the subfascial dissection of perforators during deep inferior
      epigastric artery perforator flap harvest: the hydrodissection technique.

PMID- 20679801
TI  - A novel technique for nipple-sparing mastectomy and immediate reconstruction in
      patients with macromastia.

PMID- 20679802
TI  - Attitudes toward biological mesh in breast reconstruction: a regional survey of
      plastic surgeons.

PMID- 20679803
TI  - Removing highly cohesive silicone gel after breast implant rupture: an in vitro
      study.

PMID- 20679804
TI  - Chest wall spindle cell fibromatosis after breast augmentation.

PMID- 20679805
TI  - Sternal stenting and vascular conduit coverage with combined
      interposition/overlay rib grafts.

PMID- 20679806
TI  - Umbilical shape by age and growth: a Japanese study.

PMID- 20679807
TI  - The future in perforator flap imaging: a new technique to substantially reduce
      radiation dose with computed tomographic angiography.

PMID- 20679808
TI  - Evaluation of free flap perfusion with dynamic contrast-enhanced magnetic
      resonance imaging.

PMID- 20679809
TI  - A new technique of expanding the underdeveloped scrotum.

PMID- 20679810
TI  - Use of bioabsorbable bone graft in osteomyelitis associated with ischial pressure
      sores.

PMID- 20679812
TI  - The communicating vein in the radial forearm free flap.

PMID- 20679811
TI  - Clinical trial of delay of the venous island flap.

PMID- 20679813
TI  - Three-dimensional arterial anatomy of the gluteus maximus and the proper method
      of muscle splitting.

PMID- 20679814
TI  - The tensile reduction effects of silicone gel sheeting.

PMID- 20679815
TI  - Plastic surgery during natural disasters: lessons from Haiti.

PMID- 20679816
TI  - The aesthetic-health pyramid: a tool for patient education.

PMID- 20679817
TI  - The impact of alpha omega alpha membership on successfully matching to residency.

PMID- 20679818
TI  - Demographic and geographic analysis of providers of cosmetic services in the
      greater Los Angeles area: 2008 to 2009.

PMID- 20679819
TI  - Defeating the negative stereotypes of plastic surgery.

PMID- 20679820
TI  - Breast reconstruction with the latissimus dorsi flap: women's preference for scar
      location.
AB  - BACKGROUND: Refinements made in latissimus dorsi breast reconstruction have
      improved the aesthetic appearance of the breast without changing the donor-site
      location. The optimal location for donor-site placement, from a patient's
      perspective, is still unknown. The purpose of this study was to assess women's
      preference for the latissimus dorsi donor-site location; the reasons for donor
      site choice; and the correlation between donor-site location preference and
      factors such as, age, body mass index, body image, and clothing options. METHODS:
      Two hundred fifty women between the ages of 20 and 80 years were surveyed.
      Participants analyzed patients' pictures and ranked the scar locations from most
      desirable to least desirable. The reason for preference and additional factors
      were assessed. The data were then collected and analyzed using contingency tables
      with p < 0.005. RESULTS: The low and middle transverse donor sites were the most
      preferred sites, 54 percent and 22 percent, respectively. The most common reasons
      for choosing a donors site were ability to conceal the scar in a low-back top and
      contour improvement. Women younger than 50 years were more concerned about the
      ability to conceal the scar (64 percent). Women older than 50 years were focused
      on contour improvement (40 percent) and concealing the scar while clothed (42
      percent) (p < 0.05). No direct correlation with age, body mass index, body image,
      or clothing options was seen. CONCLUSIONS: Women overwhelmingly prefer the low
      and middle transverse scar locations. Physicians should consider using these
      locations primarily in suitable patients, as this may improve overall patient
      satisfaction following breast reconstruction.

PMID- 20679821
TI  - Discussion: Breast reconstruction with the latissimus dorsi flap: women's
      preference for scar location.

PMID- 20679822
TI  - Inclusion of mesh in donor-site repair of free TRAM and muscle-sparing free TRAM
      flaps yields rates of abdominal complications comparable to those of DIEP flap
      reconstruction.
AB  - BACKGROUND: Pedicled and free transverse rectus abdominis musculocutaneous (TRAM)
      flaps remain popular for autologous breast reconstruction, but the incidence of
      abdominal donor-site bulge and hernia is significantly greater when compared with
      deep inferior epigastric artery perforator (DIEP) flap reconstruction. Mesh
      repair after muscle harvest, however, may reduce the complication rate to that
      observed with perforator flaps alone. METHODS: A retrospective review of all free
      flap breast reconstructions at the University of California, Los Angeles Medical
      Center from 2002 to 2007 was performed. Abdominal bulge and hernia were noted for
      patients undergoing free TRAM and muscle-sparing free TRAM flap reconstructions
      and were compared with those observed following DIEP flap reconstructions.
      RESULTS: A total of 275 free TRAM plus muscle-sparing free TRAM flaps and 200
      DIEP flaps were performed. Among patients with free and muscle-sparing free TRAM
      flaps, 11.3 percent were found to have postoperative abdominal bulge or hernia.
      Only 3.5 percent of DIEP flap patients had abdominal complications. Incorporating
      mesh into the rectus fascia repair significantly reduced the abdominal
      complications reported to 5.1 percent. Of the 86 free and muscle-sparing free
      TRAM flaps that were bilateral, 12.8 percent had hernias/bulges. Use of mesh with
      bilateral free and muscle-sparing free TRAM flaps reduced the complication rate
      to 3.7 percent. CONCLUSIONS: Incorporating mesh into rectus fascia repair in free
      and muscle-sparing free TRAM flap cases significantly reduces the rate of
      postoperative abdominal complications to levels equivalent to those for DIEP flap
      reconstructions. The authors advocate deciding intraoperatively between DIEP and
      muscle-sparing free TRAM flap dissections based on ease of dissection and
      whichever offers optimal safety and flap perfusion. Routine use of mesh in donor
      site repair will decrease postoperative abdominal morbidity in unilateral and
      bilateral cases.

PMID- 20679823
TI  - Is a second free flap still an option in a failed free flap breast
      reconstruction?
AB  - BACKGROUND: Salvage of a failed autologous breast reconstruction is a complex and
      challenging problem. The purpose of this study was to analyze the indications,
      methods, and outcomes of tertiary surgery in patients with a failed autologous
      breast reconstruction. METHODS: A retrospective chart review was performed for
      all patients who underwent breast reconstruction with autologous tissue performed
      by the senior author (M.H.) between 2002 and 2009. Special emphasis was made to
      evaluate the first reconstruction performed, causes of failure, indications for
      tertiary reconstruction, and outcomes. A preoperative hematologic workout was
      performed. For patients who were classified within the highest group of
      thromboembolism, specific prophylactic measurements were taken for the tertiary
      surgery. RESULTS: Of 688 patients who underwent autologous breast reconstruction,
      a total of 14 patients required tertiary breast reconstruction.
      Hypercoagulability was found in three patients resulting from disorders such as
      lupus anticoagulant positivity and antiphospholipid syndrome. Six patients (43
      percent) underwent a combination of local skin flaps and/or implant
      reconstructions. Eight patients (57 percent) underwent nine microvascular breast
      reconstructions: five superior gluteal artery perforator flaps, three transverse
      myocutaneous gracilis flaps, and one deep inferior epigastric artery perforator
      flap. Two of nine flaps (22 percent) required quaternary reconstructions because
      of a failure of the second free flap. Additional corrections such as revision
      lipofilling, scar revision, contralateral breast shaping, implant change, and
      capsulotomies were performed in 92.7 percent of the patients, with a mean follow
      up of 37 months (range, 6 months to 7 years). CONCLUSIONS: Tertiary surgery after
      autologous breast reconstruction failure has limited options and further
      reoperations are often needed. Careful patient history and selective blood tests
      may reveal hidden coagulation disorders. When a second free flap is planned,
      primary and secondary antithrombotic therapy should be considered.

PMID- 20679824
TI  - Relationship between venous congestion and intraflap venous anatomy in DIEP flaps
      using contrast-enhanced magnetic resonance angiography.
AB  - BACKGROUND: Deep inferior epigastric artery perforator (DIEP) flap harvest is
      associated with a significant rate of venous congestion; however, the reason for
      this has not yet been fully explained. Contrast-enhanced magnetic resonance
      angiography enables detailed evaluation of both the arterial and venous
      anatomies. METHODS: A retrospective review of DIEP flaps that underwent
      preoperative contrast-enhanced magnetic resonance angiography was performed.
      Outcomes were compared with preoperative radiologic reporting of contrast
      enhanced magnetic resonance angiographic imaging, and anatomical data from the
      scans were also analyzed. RESULTS: Review of 54 DIEP flaps with venous system
      reporting was performed. Seven DIEP flaps suffered venous congestion, all of
      which were raised on perforators without direct connections between the venae
      comitantes and the main arborization of the superficial inferior epigastric vein.
      In the 47 DIEP flaps without venous congestion, 46 were raised on at least one
      perforator with a direct venous connection between the perforator venae
      comitantes and the main arborizations of the superficial inferior epigastric
      vein. There was an extremely significant association between the absence of a
      direct connection with the perforator venae comitantes on magnetic resonance
      angiography and the occurrence of venous congestion (p < 0.0001). Sixty-eight
      percent of all perforators had direct venous connections, which were
      significantly more likely to be located in the medial row. CONCLUSIONS: DIEP
      flaps elevated on perforators with venae comitantes with direct venous
      connections to the main arborization of the superficial inferior epigastric vein
      are significantly associated with a very low incidence of flap venous congestion.
      Contrast-enhanced magnetic resonance angiography allows detailed appraisal of the
      venous anatomy, which may minimize the risk of DIEP flap venous insufficiency and
      the need for salvage procedures.

PMID- 20679825
TI  - Breast reconstruction with SGAP and IGAP flaps.
AB  - BACKGROUND: Perforator flaps represent the latest in the evolution of soft-tissue
      flaps. They allow the transfer of the patient's own skin and fat in a reliable
      manner with minimal donor-site morbidity. The powerful perforator flap concept
      allows transfer of tissue from numerous, well-described donor sites to almost any
      distant site with suitable recipient vessels. Large-volume flaps can be reliably
      supported with perforators from areas such as the buttock and transferred
      microsurgically for breast reconstruction. INDICATIONS: The ideal tissue for
      breast reconstruction is fat with or without skin, not implants or muscle.
      Absolute contraindications specific to perforator flaps in our practice include
      history of previous liposuction of the donor site, some previous donor-site
      surgery, or active smoking (within 1 month before surgery). METHODS: Perforator
      flaps are supplied by blood vessels that arise from named, axial vessels and
      perforate through or around overlying muscles and septa to vascularize the
      overlying skin and fat. During flap harvest, these perforators are meticulously
      dissected free from the surrounding muscle, which is spread in the direction of
      the muscle fibers and preserved intact. The pedicle is anastomosed to recipient
      vessels in the chest, and the donor site is closed without the use of synthetic
      mesh. CONCLUSION: Perforator flaps allow for safe, reliable tissue transfer from
      a variety of sites and provide ideal tissue for breast reconstruction, with
      minimal donor-site morbidity.

PMID- 20679826
TI  - Hyperbaric oxygen inhibits ischemia-reperfusion-induced neutrophil CD18
      polarization by a nitric oxide mechanism.
AB  - BACKGROUND: Hyperbaric oxygen decreases ischemia-reperfusion-induced
      neutrophil/intercellular adhesion molecule-1 adhesion by blocking CD18
      polarization. The purpose of this study was to evaluate whether this hyperbaric
      oxygen effect is nitric oxide dependent and to determine whether nitric oxide
      synthase is required. METHODS: A gracilis muscle flap was raised in nine groups
      of male Wistar rats. Global ischemic injury was induced by clamping the gracilis
      muscle pedicle artery and vein for 4 hours. The hyperbaric oxygen treatment
      consisted of 100% oxygen at 2.5 atm absolute during the last 90 minutes of
      ischemia. Groups were repeated with and without various nitric oxide synthase
      inhibitors and carboxy-2-phenyl-4,4,5,5,-tetramethylimidazoline-1-oxyl-3-oxide (C
      PTIO), a nitric oxide scavenger. Normal neutrophils were exposed to activated
      plasma on intercellular adhesion molecule-1-coated coverslips (percentage
      adherent) and labeled with fluorescein isothiocyanate/antirat-CD11b for confocal
      microscopy (percentage polarized). The percentage of adherent and polarized cells
      was reported as mean + or - SEM. Statistical analysis was by analysis of
      variance. A value of p < or = 0.05 was considered significant. RESULTS: C-PTIO
      treated ischemia-reperfusion/hyperbaric oxygen plasma showed a significant
      increase in the percentage polarization of CD18 compared with ischemia
      reperfusion/hyperbaric oxygen-untreated plasma from 4.1 + or - 2.5 percent to
      33.7 + or - 7.7 percent (p < or = 0.05). The nitric oxide scavenger C-PTIO also
      increased the percentage of adherent cells from 1.6 + or - 0.4 percent to 20.3 +
      or - 5.9 percent (p < or = 0.05). Administration of N-nitro-L-arginine methyl
      ester and other nitric oxide synthase inhibitors before hyperbaric oxygen
      treatment restored neutrophil adhesion and CD18 polarization to ischemia
      reperfusion control values, significantly greater than ischemia
      reperfusion/hyperbaric oxygen alone. CONCLUSION: These results suggest that the
      hyperbaric oxygen reduction of ischemia-reperfusion-induced neutrophil
      polarization of CD18 and adherence to intercellular adhesion molecule-1 is
      mediated through a nitric oxide mechanism that requires nitric oxide synthase.

PMID- 20679827
TI  - Divergent modulation of adipose-derived stromal cell differentiation by TGF-beta1
      based on species of derivation.
AB  - BACKGROUND: Adipose-derived stromal cells hold promise for skeletal tissue
      engineering. However, various studies have observed that adipose-derived stromal
      cells differ significantly in their biology depending on species of derivation.
      In the following study, the authors sought to determine the species-specific
      response of adipose-derived stromal cells to recombinant TGF-beta1 (rTGF-beta1).
      METHODS: Adipose-derived stromal cells were derived from mouse and human sources.
      Recombinant TGF-beta1 was added to culture medium (2.5 to 10 ng/ml);
      proliferation and osteogenic and adipogenic differentiation were assessed by
      standardized parameters, including cell counting, alkaline phosphatase, alizarin
      red, oil red O staining, and quantitative real-time polymerase chain reaction.
      RESULTS: Recombinant TGF-beta1 was found to significantly repress cellular
      proliferation in both mouse and human adipose-derived stromal cells (p < 0.01).
      Recombinant TGF-beta1 was found to significantly repress osteogenic
      differentiation in mouse adipose-derived stromal cells. In contrast, osteogenic
      differentiation of human adipose-derived stromal cells proceeded unimpeded in
      either the presence or the absence of rTGF-beta1. Interestingly, rTGF-beta1
      induced expression of a number of osteogenic genes in human adipose-derived
      stromal cells, including BMP2 and BMP4. CONCLUSIONS: The authors' results further
      detail an important facet in which mouse and human adipose-derived stromal cells
      differ. Mouse adipose-derived stromal cell osteogenesis is completely inhibited
      by rTGF-beta1, whereas human adipose-derived stromal cell osteogenesis progresses
      in the presence of rTGF-beta1. These data highlight the importance of species of
      derivation in basic adipose-derived stromal cell biology. Future studies will
      examine in more detail the species-specific differences among adipose-derived
      stromal cell populations.

PMID- 20679828
TI  - Utility scores for facial disfigurement requiring facial transplantation
      [outcomes article].
AB  - BACKGROUND: Controversy exists as to whether the benefits of facial
      transplantation outweigh the risk of continuous immunosuppression. Utility scores
      [range, 0 (death) to 1 (perfect health)] are a standardized tool with which to
      objectify health states or diseases and can help answer such controversy.
      METHODS: An Internet-based utility assessment study using visual analogue scale,
      time trade-off, and standard gamble was used to obtain utilities for facial
      disfigurement requiring facial transplantation from a sample of the general
      population and medical students at McGill University. Average utility scores were
      compared using t test, and linear regression was performed using age, race, and
      education as independent predictors of each of the utility scores. RESULT: A
      total of 307 people participated in the study. All measures (visual analogue
      scale, time trade off, and standard gamble) for facial disfigurement (0.46 + or -
      0.02, 0.68 + or - 0.03, and 0.66 + or - 0.03, respectively) were significantly
      different (p < 0.001) from the corresponding ones for monocular blindness (0.62 +
      or - 0.02, 0.83 + or - 0.02, and 0.82 + or - 0.02, respectively) and binocular
      blindness (0.33 + or - 0.02, 0.62 + or - 0.03, and 0.61 + or - 0.03,
      respectively). Age was inversely proportional to the utility scores in all groups
      (p < 0.01), decreasing a utility score of 0.006 for every increase in year of
      age. CONCLUSION: A sample of the general population and medical students, if
      faced with facial disfigurement, would undergo a face transplant procedure with a
      34 percent chance of death and be willing to trade 12 years of their life to
      attain perfect health.

PMID- 20679829
TI  - An algorithm for oncologic scalp reconstruction.
AB  - BACKGROUND: Modern reconstructive surgery allows for radical resection and
      reconstruction of any scalp tumor. However, a significant number of patients are
      still not treated optimally because of incomplete reconstructive guidelines.
      METHODS: The treatment of scalp tumors was documented in 60 patients over a 10
      year period. Data regarding tumor type, size, and localization; reconstructive
      procedure; oncologic, functional, and aesthetic outcome; and complications were
      collected and analyzed retrospectively. These data were correlated to recurrence
      and survival rates. The findings extracted from the data were amalgamated to
      produce the proposed reconstructive algorithm. RESULTS: Five reconstructive
      categories were defined and their application could be described in an
      algorithmic approach. Indications, limitations, and adequate reconstructive
      procedures for each category were identified. The most important decisions are
      when to use local flaps versus primary closure and when to use free tissue
      transfer. CONCLUSIONS: Radical surgical resection and reconstruction presents the
      best available method to cure scalp tumors or to establish local disease control
      in palliative settings. The authors present an algorithm to assist in the
      planning process of oncologic scalp reconstruction. If this algorithm is applied,
      the occurrence of inadequate resections and the need for repeated procedures can
      be minimized.

PMID- 20679830
TI  - Aesthetic and oncologic outcome after microsurgical reconstruction of complex
      scalp and forehead defects after malignant tumor resection: an algorithm for
      treatment.
AB  - BACKGROUND: Limited follow-up data on aesthetic outcome and survival after
      microsurgical reconstruction of complex scalp and forehead defects are available.
      These data are important to improve reconstruction quality and patient
      counseling. The purpose of this study was to evaluate surgical, aesthetic, and
      oncologic outcome of free flap scalp and forehead reconstructions in the patient
      population of two academic centers. METHODS: Retrospective data analysis of
      patients with a microsurgical reconstruction of the scalp or forehead between
      January of 1999 and June of 2008 was performed. Aesthetic outcome was assessed on
      a five-point Likert scale for flap color match, contour, and overall aesthetic
      result. RESULTS: The group consisted of 84 patients with a mean follow-up time of
      27 months (range, 1 to 95 months). Mean defect size was 134 cm (range, 20 to 340
      cm), with 46 percent full-thickness bone defects and 16 percent dura defects. The
      most commonly used free flaps were latissimus dorsi (n = 34) and anterolateral
      thigh (n = 24). Total flap failure occurred in five patients (6 percent). Disease
      free survival and overall survival rates at 5 years were 57 and 65 percent,
      respectively. Additional operations for aesthetic reasons were performed in 19
      patients (23 percent). Panel scores showed a significant lower satisfaction with
      reconstruction of defects that were located over the frontal scalp compared with
      other locations (p = 0.004). CONCLUSIONS: Microsurgical reconstruction in complex
      scalp and forehead defects is a safe procedure. From the authors' experience,
      they suggest an algorithm for reconstruction of these complex reconstructive
      defects that will most likely result in the best aesthetic result.

PMID- 20679831
TI  - Reconstruction of the esophagus and voice.
AB  - BACKGROUND: Esophageal defects are reconstructed using a variety of methods and
      tissue types. The choice depends on the location of the defect, the condition of
      the patient, and the flaps that are available for reconstruction. Often, patients
      with esophageal defects also lack a mechanism for voice production following a
      total laryngectomy procedure. METHODS: A review of the literature was performed
      for esophagus reconstruction and voice rehabilitation following laryngectomy.
      Methods of voice restoration using intestinal transfers are presented based on
      the authors' experience. RESULTS: Several methods of esophagus and voice
      restoration can achieve excellent functional outcomes. CONCLUSION: Esophagus
      reconstruction and voice rehabilitation following esophageal resection and total
      laryngectomy are possible using a variety of flaps with good functional outcomes.

PMID- 20679832
TI  - Suspension of the brow in facial paralysis and frontalis loss.

PMID- 20679833
TI  - A modified technique for inferior turbinate reduction: the integration of
      coblation technology.
AB  - BACKGROUND: Many procedures have been described for the surgical management of
      inferior turbinate hypertrophy. Coblation is a relatively new technology that
      uses radiofrequency energy to ablate hypertrophied tissues. The standard method
      of using this technology has been shown to be effective; however, it only
      partially relieves symptoms of obstruction. The authors present a modified hybrid
      technique for the surgical reduction of inferior turbinate hypertrophy using a
      combination of coblation and turbinate outfracture to maximize the nasal airway
      patency. METHODS: A review was performed of operating room video files to
      evaluate the senior author's (J.L.E.) technique for performing inferior turbinate
      reduction using the modified coblation and outfracture technique. The videos were
      edited to present the technique. RESULTS: The senior author has found this
      modified hybrid technique to be both efficacious and safe. This Video Plus
      article presents both the operative technique and postoperative management for
      cases of inferior turbinate hypertrophy that fail medical management. CONCLUSION:
      This modified hybrid technique is the mainstay of the senior author's treatment
      of inferior turbinate hypertrophy reduction and can be a useful surgical tool to
      achieve adequate outcomes when dealing with patients who have hypertrophied
      inferior turbinates that fail medical management.

PMID- 20679834
TI  - Supermicrosurgery in peroneal and soleus perforator-based free flap coverage of
      foot defects caused by occlusive vascular diseases.
AB  - BACKGROUND: Limb salvage rates for lower limbs have improved tremendously for
      trauma and tumor victims. The optimal solution for coverage of defects caused by
      ischemic limbs does not exist. The authors believe the use of supermicrosurgery
      and perforator flap surgery might add a further tool useful to the reconstructive
      surgeon. METHODS: After excisional debridement of the wound, under loupe
      magnification, branches of the terminal foot vessels were sought. Once identified
      and deemed suitable, the thin peroneal flaps were isolated based on perforator
      vessels. The flaps raised were either peroneal perforator-based or soleus
      perforator-based flaps. Microanastomosis was performed at the perforator level
      with 10-0 or 11-0 Ethilon sutures, and the flap was inset. The donor site was
      closed primarily. RESULTS: A total of 18 such flaps were raised in 17 patients
      with 15 septocutaneous and three musculocutaneous perforators. Sixteen peroneal
      perforator-based flaps and two soleus perforator-based flaps were used. There was
      one major (flap loss) and two minor (wound dehiscence) complications. The rest of
      the patients healed well, with no recurrence at a mean follow-up of 8.3 months.
      CONCLUSIONS: Limb salvage in ischemic limbs is now possible with
      supermicrosurgery and perforator flaps. This method allows contour resurfacing,
      avoids bulky tissue, is fast, and can be performed under regional anesthesia.

PMID- 20679835
TI  - Topical silicone gel versus placebo in promoting the maturation of burn scars: a
      randomized controlled trial.
AB  - BACKGROUND: Silicone sheets are widely used in the treatment of hypertrophic
      scars, although application around joints may cause limited adherence and reduced
      movement. To approach these problems, a topical silicone gel was developed that
      can be applied easily in a thin layer, and that is nonrestrictive and less
      apparent. The objective of this study was to investigate the effectiveness of
      topical silicone gel in promoting the maturation of burn scars. METHODS: Forty
      six scars on 23 patients were included in a randomized, placebo-controlled,
      within-subject comparative, double-blinded, clinical trial and followed for 1
      year. The mean age of the scars at inclusion was 4 months. Effectiveness on scar
      quality was evaluated using the Patient and Observer Scar Assessment Scale and
      the DermaSpectrometer. Significance was tested using repeated measures analyses
      and Wilcoxon paired-sample signed rank tests. RESULTS: Over all visits, the
      benefit on surface roughness was statistically significant (p = 0.012). At
      individual time points, the surface of the topical silicone gel-treated scars
      showed significantly less roughness (p = 0.014) at 3 months after start of the
      treatment, and the topical silicone gel-treated scars were significantly less
      itchy (p = 0.018 and p = 0.013, respectively) at 3 and 6 months. CONCLUSION:
      Topical silicone gel significantly improves the surface roughness of burn scars,
      and patients experience significantly less itching in the first half year after
      application.

PMID- 20679836
TI  - Long-term evaluation of elongating columella using conchal composite graft in
      bilateral secondary cleft lip and nose deformity.
AB  - BACKGROUND: A short columella is one of the most severe problems in bilateral
      cleft lip and nose deformity. In particular, with tissue insufficiency or scar
      contracture on the upper lip, it is very hard to achieve a good nasal profile
      with conventional methods. METHODS: One hundred thirty-seven patients with a
      short columella were operated on from February of 1987 to December of 2008. The
      average age at operation was 7.3 years. The conchal cartilage was harvested. The
      preauricular or postauricular skin-subcutaneous fat composite tissue was
      harvested. Through a transcolumellar incision, the conchal cartilage was inset
      and the defect was covered with skin-fat composite tissue. The serial nasal
      profiles were evaluated before and after surgery. Also, the postoperative nasal
      profiles were compared with normal profiles. The postoperative color difference
      with surrounding skin was measured by the L*a*b* photographic analysis method.
      RESULTS: The mean height and width of skin-subcutaneous fat composite tissue were
      9.81 and 22.14 mm, respectively. The preoperative and postoperative measuring for
      columella height was 5.1 + or - 1.1 mm and 14.2 + or - 1.5 mm. The columella-lip
      angle was 120.30 + or - 12.97 preoperatively degrees and 98.76 + or - 10.98
      degrees postoperatively, whereas the angle of columellar-alar triangle was 111.56
      + or - 11.39 degrees and 97.91 + or - 11.49 degrees, respectively. None of the
      postoperative profiles were different from those of normal Korean people of the
      same age except in the 0- to 6-year-old group (p < 0.05). The color match was
      best with preauricular composite tissue. Complications included total necrosis in
      three cases and partial necrosis in 12 cases that were treated conservatively.
      CONCLUSION: Elongating columella using a composite graft can be a satisfying
      alternative, especially for a severe short columella with upper lip tissue
      deficiency.

PMID- 20679837
TI  - Optimizing closed reduction of nasal and zygomatic arch fractures with a mobile
      fluoroscan.
AB  - BACKGROUND: Although closed reductions of nasal fractures and zygomatic arch
      fractures are considered minor procedures, improper reductions are not uncommon.
      Objectively evaluating reduction adequacy with imaging assistance during surgery
      is crucial. The authors used mobile Fluoroscan intraoperatively to assess the
      adequacy of closed reduction for nasal fractures and zygomatic arch fractures.
      METHODS: Patients with nasal fractures or zygomatic arch fractures who underwent
      surgery between 2000 and 2004 were enrolled. Results were reviewed according to
      postoperative photographs and radiography. Scoring systems were designed for
      objective assessment, with higher scores representing better outcome. RESULTS:
      One hundred eight patients with nasal fractures and 36 patients with zygomatic
      arch fractures were enrolled. Fifty-three patients underwent closed reduction of
      the nasal fracture with fluoroscopic assistance (group NF) and 55 patients
      underwent closed reduction without fluoroscopic assistance (group N). The mean
      scores for the fluoroscopic assistance group was 2.96 for radiography and 2.91
      for photography, compared with 2.58 for radiography and 2.67 for photography for
      the group without fluoroscopic assistance. The difference was significant for
      radiography (p = 0.001) but not for photography (p = 0.068). Of the patients with
      zygomatic arch fractures, 16 were repaired with fluoroscopic assistance (group
      ZF) and 20 were repaired without fluoroscopic assistance (group Z). The average
      score for group ZF was 2.81 for radiography and 2.94 for photography, compared
      with 2.45 for radiography and 2.6 for photography in group Z. There were
      significantly higher scores for group ZF for both radiography and photography.
      CONCLUSION: The mobile Fluoroscan provides direct visualization of the fracture
      site and instruments and improves the outcomes of closed reduction.

PMID- 20679838
TI  - Three-dimensional airway changes after Le Fort III advancement in syndromic
      craniosynostosis patients.
AB  - BACKGROUND: To investigate the changes of upper airway volume in syndromic
      craniosynostosis patients following Le Fort III advancement, computed tomographic
      scans were analyzed and related to the amount of advancement. METHODS: In this
      retrospective study, the preoperative and postoperative computed tomographic
      scans of 19 patients with syndromic craniosynostosis who underwent Le Fort III
      advancement were analyzed. In four cases, preoperative polysomnography
      demonstrated obstructive sleep apnea. The airway was segmented using a
      semiautomatic region growing method with a fixed Hounsfield threshold value.
      Airway volumes of hypopharynx and oropharynx (compartment A) and nasopharynx and
      nasal cavity (compartment B) were analyzed separately, as was the total airway
      volume. Advancement of the midface was recorded using lateral skull radiographs.
      Data were analyzed for all patients together and for patients with
      Crouzon/Pfeiffer and Apert syndromes separately. RESULTS: Airway volume increased
      significantly in compartment A (20 percent; p = 0.044) and compartment B (48
      percent; p < 0.001), as did total airway volume in (37 percent; p < 0.001) in the
      total study group. No significant differences in volume changes were found
      comparing Apert with Crouzon/Pfeiffer patients. No distinct relation could be
      found between advancement of the midface and volume gain either in the total
      study group or in Apert and Crouzon/Pfeiffer patient groups separately.
      Postoperative polysomnography showed significant improvement of obstructive sleep
      apnea in all four patients. CONCLUSIONS: A significant improvement of the upper
      airway after Le Fort III advancement in syndromic craniosynostosis patients is
      demonstrated. No distinct relation could be observed between advancement and
      airway volume changes.

PMID- 20679839
TI  - Management of isolated sagittal synostosis in the absence of scaphocephaly: a
      series of eight cases.
AB  - BACKGROUND: The diagnosis of isolated sagittal synostosis is usually made at
      birth, with a boat-shaped deformity of the skull (scaphocephaly). The Oxford
      Craniofacial Unit has successfully managed eight cases of isolated sagittal
      synostosis without scaphocephaly. To the authors' knowledge, there have been no
      reports of this in the literature. METHODS: The Oxford Craniofacial Unit database
      (set up in 2004) was searched. This identified 193 cases of isolated sagittal
      synostosis, eight of which did not have a scaphocephalic head shape (i.e., a
      cephalic index <76). RESULTS: Patients with isolated sagittal synostosis in the
      absence of scaphocephaly represent 4.1 percent of all isolated sagittal
      synostosis patients in the authors' database. Intracranial pressure was measured
      in six of the eight cases and found to be high in four of these (67 percent).
      CONCLUSIONS: It is unclear why the secondary features of sagittal synostosis did
      not develop in these cases. Possible explanations include fusion of the suture
      late after the majority of skull growth has taken place and a patent metopic
      suture allowing growth to occur anteriorly; other sutures appeared patent
      radiologically but may not have been functioning normally. Although difficult to
      recognize, patients with isolated sagittal synostosis in the absence of
      scaphocephaly are important to identify because they are at high risk of
      developing raised intracranial pressure. A new management algorithm for treatment
      of these cases is described that has been used successfully in the Oxford
      Craniofacial Unit.

PMID- 20679840
TI  - The subplatysmal supramylohyoid fat.
AB  - BACKGROUND: Liposuction of the neck has an established role in selected patients
      undergoing cervicoplasty. Some authors have suggested a role for subplatysmal fat
      removal. Observations in the anatomy laboratory suggested the presence of
      discrete regions of subplatysmal fat. This information may be useful during
      surgical procedures in the subplatysmal plane. METHODS: Five fresh cadaver
      dissections were performed. There were four male specimens and one female
      specimen with an age range of 66 to 78 years. Sequential dissection of the
      cervical layers included skin, supraplatysmal fat, platysma muscle, and
      subplatysmal fat. Loupe magnification was used to aid dissection. RESULTS:
      Subplatysmal fat is found in three compartments: central, medial, and lateral.
      Their relationship to the platysma and digastric muscles is consistent. The
      mylohyoid muscle represents the posterior boundary of these compartments. Central
      fat is easily distinguished from medial and lateral fat due to differences in
      color and appearance. These three compartments abut one another and together form
      the subplatysmal fat layer. Differences in thickness of these compartments were
      noted. CONCLUSIONS: Subplatysmal fat occurs as distinct regions. These can be
      identified during surgery by their relationship to the platysma, digastric, and
      mylohyoid muscles. Knowledge of the regional differences in appearance is a
      further aid in identification. Knowledge of this anatomy can facilitate
      dissection when performed in the subplastysmal plane.

PMID- 20679841
TI  - Validation of a photonumeric wrinkle assessment scale for assessing nasolabial
      fold wrinkles.
AB  - BACKGROUND: Reliable clinical assessment tools are needed to evaluate the effects
      of injectable devices and fillers. This study was designed to validate a new
      photonumeric wrinkle assessment scale using standardized photographic methodology
      to obtain reference photographs. METHODS: Multiple photographs (test set) from
      approximately 78 volunteer subjects with varying degrees of severity of the
      left/right nasolabial fold wrinkles were examined. Photographs of 18 subjects
      representing the full spectrum of nasolabial fold wrinkle severity were selected
      from the test set by a study team of three independent physicians and were
      classified using a six-point scale (0 = no wrinkles; 5 = very deep wrinkle,
      redundant fold). One representative photograph was identified by study team
      consensus for each of the six scale points. Photographs were randomly arranged in
      booklets for a second, independent, group of five physician raters to grade both
      left/right nasolabial fold wrinkles twice over a 2-week interval. The scale was
      considered valid if interevaluator reliability, as measured by intraclass
      correlation coefficient, was greater than or equal to 80 percent. RESULTS:
      Intrarater reliability was significant (p < 0.001) for all five physicians and
      overall, with Pearson correlation coefficients greater than 92 percent in all
      cases. The overall weighted kappa coefficient for intrarater reliability for all
      five raters was 0.598 (range, 0.433 to 0.684). The overall interrater reliability
      kappa value was 0.525, and a high degree of interrater reliability was observed
      at week 1 and week 2 time points (intraclass correlation coefficient = 0.890 and
      0.880, p < 0.001 for both), validating the new wrinkle assessment scale.
      CONCLUSION: This study validates the new wrinkle assessment scale, which provides
      a reliable clinical tool for use in nasolabial fold wrinkle evaluation.

PMID- 20679842
TI  - Nutritional assessment of bariatric surgery patients presenting for plastic
      surgery: a prospective analysis.
AB  - BACKGROUND: Assessment of nutritional status in the growing postbariatric patient
      population remains controversial. Previous literature suggests that these
      patients have poor nutrition that may have adverse effects on surgical outcomes.
      The authors sought to determine the optimal method of nutritional assessment in
      postbariatric patients. METHODS: One hundred patients presenting for body
      contouring after bariatric surgery were consecutively enrolled in an
      institutional review board-approved prospective study. A trained nutritionist
      assessed protein and calorie intake. All patients underwent baseline laboratory
      assessment. RESULTS: Eighteen percent of subjects had less than the recommended
      daily protein intake. Hypoalbuminemia was observed in 13.8 percent of subjects,
      with hypoprealbuminemia in 6.5 percent. Nearly forty percent of all patients had
      evidence of iron deficiency, with vitamin B12 deficiency present in 14.5 percent.
      Ten percent of subjects (all women) were confirmed to have iron deficiency
      anemia. Impaired fasting glucose was seen in 6.2 percent of subjects, whereas 3.6
      percent had hemoglobin A1c levels greater than 6.5. Increasing age (odds ratio,
      1.07) and greater change in body mass index (odds ratio, 1.11) were predictors of
      low protein intake. Dumping syndrome led to 13.3 times increased odds of low
      albumin levels. CONCLUSIONS: The results suggest that inadequate nutrition is
      common among postbariatric patients presenting for body contouring. The lack of
      correlation between methods of nutritional assessment supports the combination of
      multiple methods in determining overall nutritional status. The presence of
      dumping syndrome, a large change in body mass index, and advanced age may help to
      identify patients with an increased risk of nutritional deficiency.

PMID- 20679843
TI  - Developing good clinical questions and finding the best evidence to answer those
      questions.
AB  - Evidence-based medicine involves the integration of the best scientific evidence
      available with physician experience and patient preferences. One of the first
      steps in evidence-based medicine involves developing a question based on issues
      encountered with patients or a disease and finding evidence to answer the
      question. This article is a guide to plastic surgeons in how to begin the
      practice of evidence-based medicine by developing clinical questions and finding
      evidence to answer these questions.

PMID- 20679846
TI  - Discussion: plastic surgery chief resident clinics: the current state of affairs.

PMID- 20679844
TI  - Identifying and avoiding bias in research.
AB  - This narrative review provides an overview on the topic of bias as part of a
      series of articles in Plastic and Reconstructive Surgery on evidence-based
      medicine. Bias can occur in the planning, data collection, analysis, and
      publication phases of research. Understanding research bias allows readers to
      critically and independently review the scientific literature and avoid
      treatments that are suboptimal or potentially harmful. A thorough understanding
      of bias and how it affects study results is essential for the practice of
      evidence-based medicine.

PMID- 20679845
TI  - Plastic surgery chief resident clinics: the current state of affairs.
AB  - BACKGROUND: One of the goals of plastic surgery residency programs is to provide
      effective training in aesthetic surgery. Recently, programs have adopted the idea
      of chief clinics to provide senior residents with the opportunity to perform
      cosmetic surgery with an increased level of autonomy. The goal of this article is
      to characterize chief clinics currently in place and their usefulness in
      providing effective training in plastic surgery under the precepts set forth by
      the Accreditation Council for Graduate Medical Education. METHODS: A survey was
      created focusing on six broad categories: respondent identifier, clinic
      structure, clinic monetary earnings, patient demographics, procedures, and
      educational utility. Surveys were distributed to all plastic surgery residency
      programs targeting current and recently graduated chief residents, and program
      directors. RESULTS: A total of 123 surveys were returned. Eighty of the 88
      plastic surgery residency programs (91 percent) were represented. Of the programs
      responding, 71.3 percent (57 programs) had a chief resident clinic. Thirty-two of
      the respondents (43.8 percent) reported that 100 percent of the procedures
      performed were cosmetic in nature. Programs differed widely on their frequency of
      occurrence and support staff available. A majority of respondents felt these
      clinics enhanced resident understanding of the six Accreditation Council for
      Graduate Medical Education core competencies. CONCLUSIONS: A majority of plastic
      surgery training programs use the chief clinic model to enhance resident
      education. These clinics vary in makeup and case distribution but serve as an
      effective way of teaching autonomy, surgical maturity, and the six Accreditation
      Council for Graduate Medical Education core competencies.

PMID- 20679847
TI  - Discussion: professional perceptions of plastic and reconstructive surgery: what
      primary care physicians think.

PMID- 20679848
TI  - Plastic surgeon compliance with national safety initiatives: clinical outcomes
      and "never events".
AB  - BACKGROUND: Venous thromboembolism and surgical-site infection have been
      identified as preventable complications that are addressed by the National
      Quality Forum and the Surgical Care Improvement Project. The authors examined
      compliance of faculty with venous thromboembolism and surgical-site infection
      prophylaxis and incidence of adverse outcomes in patients at risk. METHODS: The
      authors performed retrospective chart reviews on 243 patients who underwent
      abdominoplasty or panniculectomy from 2000 to 2007 and documented demographics
      and adverse outcomes. Analysis was completed using Pearson's chi-square and
      Fisher's exact test for categorical variables. Significance was set at p < 0.05.
      Obesity was defined as body mass index more than 30 and morbid obesity was
      defined as body mass index more than 40. RESULTS: Of 243 patients, 144 (59
      percent) were obese. Seventeen patients (7 percent) suffered complications. All
      243 patients received at least one form of venous thromboembolism prophylaxis.
      One patient had a deep venous thrombosis, and two had pulmonary embolism. These
      three patients were morbidly obese. Seventy-four percent of patients received
      appropriate antibiotics. Thirteen patients (5.3 percent) developed significant
      postoperative infection requiring hospitalization, 12 (92 percent) of whom
      received appropriate antibiotics. Eleven of these 13 patients (85 percent) were
      obese, and seven (54 percent) were morbidly obese. Obesity proved to be the only
      significant risk factor (p > 0.05). CONCLUSIONS: Despite very good compliance
      with safe practice initiatives, significant adverse outcomes occurred. Obesity
      was the only pervasive risk factor. This study highlights the potential need for
      compliance with quality measures and demonstrates that adverse outcomes may
      result despite adherence to best surgical practices.

PMID- 20679851
TI  - Questions on surgical treatment of migraine.

PMID- 20679849
TI  - Canary in a coal mine: does the plastic surgery market predict the american
      economy?
AB  - BACKGROUND: Economic tools have been used in the past to predict the trends in
      plastic surgery procedures. Since 1992, U.S. cosmetic surgery volumes have
      increased overall, but the exact relationship between economic downturns and
      procedural volumes remains elusive. If an economic predicting role can be
      established from plastic surgery indicators, this could prove to be a very
      powerful tool. METHODS: A rolling 3-month revenue average of an eight-plastic
      surgeon practice and various economic indicators were plotted and compared. An
      investigation of the U.S. procedural volumes was performed from the American
      Society of Plastic Surgeons statistics between 1996 and 2008. The correlations of
      different economic variables with plastic surgery volumes were evaluated. Lastly,
      search term frequencies were examined from 2004 to July of 2009 to study
      potential patient interest in major plastic surgery procedures. RESULTS: The self
      payment revenue of the plastic surgery group consistently proved indicative of
      the market trends approximately 1 month in advance. The Standard and Poor's 500,
      Dow Jones Industrial Average, National Association of Securities Dealers
      Automated Quotations, and Standard and Poor's Retail Index demonstrated a very
      close relationship with the income of our plastic surgery group. The frequency of
      Internet search terms showed a constant level of interest in the patient
      population despite economic downturns. CONCLUSIONS: The data demonstrate that
      examining plastic surgery revenue can be a useful tool to analyze and possibly
      predict trends, as it is driven by a market and shows a close correlation to many
      leading economic indicators. The persisting and increasing interest in plastic
      surgery suggests hope for a recovering and successful market in the near future.

PMID- 20679853
TI  - Reconstruction of composite posterolateral mandibular defects.

PMID- 20679854
TI  - Role of propranolol in the management of periocular hemangiomas.

PMID- 20679855
TI  - Breast reconstruction: an alternative viewpoint.

PMID- 20679857
TI  - Late Free TRAM Flap Vascular Compromise.

PMID- 20679859
TI  - Serial breast magnetic resonance imaging to enhance safety following autologous
      fat injection after breast cancer?

PMID- 20679860
TI  - Fat grafting according to Coleman for the treatment of radial nerve neuromas.

PMID- 20679861
TI  - Skin graft take at the anterolateral thigh donor site.

PMID- 20679863
TI  - Advancements in free flap monitoring in the last decade: a critical review.

PMID- 20679865
TI  - The need for randomized controlled trials in preoperative perforator imaging
      techniques.

PMID- 20679867
TI  - On the multiple-procedure approach to body contouring in the massive weight loss
      patient.

PMID- 20679870
TI  - Penile reconstruction: is the radial forearm flap the standard technique?

PMID- 20679871
TI  - Mangled extremity severity score in foot and ankle free flap reconstruction.

PMID- 20679873
TI  - Psychosocial predictors of an interest in cosmetic surgery among young Norwegian
      women: a population-based study.

PMID- 20679874
TI  - So you want to be an expert.

PMID- 20679878
TI  - Advancement in the examination of the human cardiac sinus node: an unexpected
      architecture and a novel cell type could interest the forensic science.
AB  - We have investigated the morphology of the sinus node of the human cardiac
      conduction system. Until today the sinus node (SN) is described as a
      heterogeneous system composed of 2 types of cells, namely, P or pale and T or
      transitional cells which are immersed in the matrix around the sinus nodal
      artery. T cells are said to share characteristics of P cells and of peripheral
      working atrial myocardial cells. This study was carried out on autoptic and
      explanted specimens using histochemical, immunohistochemical, and electron
      microscopic methods.Our investigations show that SN tissue has a quite different
      cellular composition, ie, spherical and/or star-shaped cells organized in
      clusters with long cytoplasmic processes (type P), transitional cells, similar to
      myocytes but with a reduced number of sarcomeres (type T) and, finally, as yet
      not described in the literature, fibroblast-like cells with long bi-tripolar
      extensions contacting cells. Interestingly, SN is squared by connective and
      elastic fibers geometrically arranged. Immunohistochemistry shows that the 3 cell
      types of the SN node express mesenchymal markers revelatory of their
      embryological origin. Innervation appears to be more complex than previously
      thought; we identified a system of synaptophysin-positive cholinergic vesicles
      dependent on the sympathetic system and parasympathetic fibers expressing S100
      protein.Overall results indicate that the SN has an unexpected, systematic
      architecture.

PMID- 20679879
TI  - An immunohistochemical profile of the so-called bile duct adenoma: clues to
      pathogenesis.
AB  - The so-called bile duct adenoma and peribiliary glands are characterized by the
      expression of two foregut antigens (designated D10 and 1F6) and secretion of acid
      mucin. On account of this similarity in phenotype and their frequent close
      association with a large caliber bile duct, it was earlier suggested that bile
      duct adenoma represent a peribiliary gland hamartoma. Here, we compare the
      expression of 13 tissue antigens in bile duct adenomas, other benign bile duct
      lesions, and various foregut-derived tissues, to further investigate the bile
      duct adenoma phenotype and pathogenesis. Antibodies to 4 intestinal mucins, 3
      cytokeratins, and CDX2, were not informative. Five foregut antigens (D10, 1F6,
      MUC6, MUC5AC, and TFF2) and secretion of acid mucin were of use in distinguishing
      bile duct adenoma from other hepatic lesions. 1F6 and MUC6 were normally present
      in bile ductules and canals of Hering, whereas the epithelium lining the larger
      bile ducts stained focally for D10, MUC5AC, MUC6, or TFF2 in, respectively, 21%,
      36%, 43%, and 100% of the livers examined. Thirty-six bile duct adenomas examined
      were distinguished by expression of MUC6 (94% of bile duct adenoma), MUC5AC
      (90%), TFF2 (80%), D10 (67%), and 1F6 (61%), and varying degrees of acid mucin
      secretion (100%). Of 30 bile duct adenoma tested for all 5 antigens, 40%
      expressed all 5, 27% expressed 4, 17% expressed 3, 13% expressed 2, and 1
      expressed only MUC6. Peribiliary glands invariably expressed D10, 1F6, MUC6, and
      TFF2, and showed acid mucin secretion, with MUC5AC present in the inflamed
      peribiliary glands of 3/4 livers with recurrent pyogenic cholangitis, but none of
      the glands of the other 23 normal or diseased livers tested. The acini of pyloric
      gland metaplasia in gallbladder and terminal ileum also stained for D10, 1F6,
      MUC6, and TFF2, with MUC5AC focally present in the gastric foveolar metaplasia
      overlying the pyloric gland metaplasia but not in the metaplastic glands. MUC6
      was expressed in 92% of ductular reactions, 1F6 in 42%, and D10 in 25%. Focal
      expression of MUC6, or TFF2 was observed in 1 or 2 examples of 14 von Meyenburg
      complexes and 6 polycystic livers, with staining for acid mucin generally obvious
      only in the glycocalyx of the epithelium of these two types of lesions. The
      distinguishing feature of so-called bile duct adenoma is their display of the
      same phenotype as pyloric gland metaplasia. It is concluded that they develop as
      a localized biliary healing response equivalent to the function of a peribiliary
      gland or pyloric gland metaplasia in the foregut.

PMID- 20679880
TI  - Primary Rosai-Dorfman disease of bone: a clinicopathologic study of 15 cases.
AB  - Sinus histiocytosis with massive lymphadenopathy or Rosai-Dorfman disease (RDD)
      is a rare histiocytic proliferative disorder of unknown etiology. Most patients
      present with lymph node involvement manifesting as adenopathy; however, RDD may
      arise primarily in a variety of extranodal sites, including bone. We report
      herein our experience with 15 cases of primary intraosseous RDD. The patients
      include 8 females and 7 males, who ranged in age from 3 to 56 (mean 27) years.
      The lesions arose in a variety of anatomical locations, including the tibia,
      femur, clavicle, skull, maxilla, calcaneus, phalanx, metacarpal, and sacrum.
      Radiographically, the lesions were lytic with well defined and usually sclerotic
      margins. Histologically, the lesions demonstrated the classic features of RDD and
      consisted of a mixed inflammatory infiltrate with numerous large histiocytes with
      abundant eosinophilic cytoplasm which exhibited emperipolesis. Some cases also
      contained numerous neutrophils. Immunohistochemical stains showed that the large
      histiocytes were S-100 positive. Follow-up information was available for 12
      patients. Five patients eventually developed additional extraosseous
      manifestations, including testicular, lymph node, and subcutaneous lesions. One
      of these 5 also developed a new bony lesion within the sternum. One patient
      developed additional lesions within multiple bones of the hand and wrist, without
      extraosseous disease. One patient had stable bony lesions, whereas 5 remained
      disease free after treatment.

PMID- 20679882
TI  - A novel tumor grading scheme for chromophobe renal cell carcinoma: prognostic
      utility and comparison with Fuhrman nuclear grade.
AB  - Chromophobe renal cell carcinoma (RCC) is a histologic subtype of RCC that
      portends a favorable prognosis. It is controversial whether the Fuhrman nuclear
      grade of chromophobe RCC has prognostic utility. Irregular nuclei, prominent
      nucleoli, and nuclear pleomorphism are inherently present in chromophobe RCC.
      Hence, the Fuhrman nuclear grade is higher even though the majority of these
      tumors have a favorable outcome. In this study, the prognostic utility of a novel
      3-tiered tumor grading system in which the innate nuclear atypia of chromophobe
      RCC was discounted, herein referred to as chromophobe tumor grade from a series
      of 124 chromophobe RCC, was compared with Fuhrman nuclear grade. Chromophobe
      tumor grade is based on the assessment of geographic nuclear crowding and
      anaplasia. The Fuhrman nuclear grade distribution between the tumors was grade 1
      (1%), grade 2 (19%), grade 3 (74%), and grade 4 (6%), whereas the chromophobe
      tumor grade distribution was grade 1 (74%), grade 2 (16%), and grade 3 (10%).
      Neither Fuhrman nuclear grade nor chromophobe tumor grade was significantly
      associated with patient's age or sex and chromophobe RCC cell types, but both
      showed a significant association with tumor size. Both Fuhrman nuclear grade and
      chromophobe tumor grade showed statistically significant positive associations
      with broad alveolar growth, necrosis, vascular invasion, and with pathologic
      stage; however, all these associations tended to be dictated by tumors with
      sarcomatoid change. When tumors with sarcomatoid change were excluded, a strong
      positive association persisted between chromophobe tumor grade and pathologic
      stage. In contrast, there was no such association between Fuhrman nuclear grade
      and stage in nonsarcomatoid chromophobe RCCs. Characterizing aggressive
      chromophobe RCC with aggressive behavior with the time from surgery to first
      occurrence of metastasis, local recurrence, or death owing to disease, we found
      that both Fuhrman nuclear grade and chromophobe tumor grade were highly
      associated with adverse outcome. However, as with the pathologic stage, only a
      significant association between chromophobe tumor grade and outcome was retained
      among nonsarcomatoid chromophobe RCCs. Multivariable Cox regression analysis also
      tended to support chromophobe tumor grade rather than Fuhrman nuclear grade as an
      independent predictor of adverse outcome, controlling for other univariably
      significant risk factors [estimated relative hazard=3.68 (P=0.026) vs. 1.86
      (P=0.42)]. In conclusion, the novel chromophobe tumor grading system proposed
      herewith provides superior prognostic value to that of the Fuhrman nuclear grade
      in chromophobe RCC and will potentially help stratify patients of chromophobe RCC
      who are at a greater risk of disease progression.

PMID- 20679881
TI  - Gall bladder and extrahepatic bile duct lymphomas: clinicopathological
      observations and biological implications.
AB  - Lymphomas of the gall bladder and extrahepatic bile ducts are exceedingly rare.
      We present the clinicopathological features of 19 cases from our files; 14
      patients had primary lymphoma (13 involving gall bladder and 1 involving common
      hepatic duct), while 5 had systemic lymphoma on further work-up. Most patients
      presented with symptoms mimicking cholecystitis. The most common primary lymphoma
      types were diffuse large B-cell lymphoma, extranodal marginal zone lymphoma, B
      lymphoblastic lymphoma, and follicular lymphoma. Two cases had features of
      lymphomatous polyposis, one a case of follicular lymphoma and the second a case
      of mantle cell lymphoma, with disease limited to the mantle zones, so-called in
      situ mantle cell lymphoma. Other rare lymphoma subtypes not described earlier in
      this site included the extracavitary variant of primary effusion lymphoma and
      plasmablastic lymphoma. Patients with diffuse large B-cell lymphoma and
      extranodal marginal zone lymphoma were older (mean age 75.8 y) than those with
      other subtypes (mean age 47 y) and more likely to have gallstones (60% vs.
      12.5%). A comprehensive literature review revealed 36 primary gall bladder and 16
      primary extrahepatic bile duct lymphomas. When compared with primary gall bladder
      lymphomas, those involving the extrahepatic bile ducts present at a younger age
      (47 y vs. 63 y) usually with obstructive jaundice, and are less often associated
      with gallstones (17% vs. 50%) or regional lymph node involvement (6% vs. 31%). In
      conclusion, primary lymphomas of the gall bladder and extrahepatic bile ducts
      show a broad spectrum of disease types, but in many respects mirror the spectrum
      of primary lymphomas of the gastrointestinal tract.

PMID- 20679883
TI  - Molecular testing for lipomatous tumors: critical analysis and test
      recommendations based on the analysis of 405 extremity-based tumors.
AB  - Ancillary molecular testing has been advocated for diagnostic accuracy in the
      differentiation of lipomas from atypical lipomatous tumors/well-differentiated
      liposarcomas (ALT/WDL); however, the implications and specific indications for
      use are not well-established in the current literature. Herein, we extend
      previous findings by quantitatively evaluating the impact of molecular testing of
      lipomatous neoplasms in our routine clinical practice, how it modifies the
      historical perspective of their clinical course, and the effect of distinct
      surgical procedures in modulating the risk of local recurrence for these tumors
      after molecular classification. On the basis of these analyses, we suggest a
      specific set of basic recommendations for complementary molecular assessment in
      the diagnosis of lipomatous tumors. Four hundred and five lipomatous neoplasms
      located in the trunk and extremities were analyzed histologically and for the
      presence of 12q13-15 amplification on paraffin-embedded tissues by assessing
      MDM2/CPM amplification. Survival analyses were calculated with Kaplan-Meier and
      compared with the log-rank. Multivariate analysis was evaluated by the Cox
      regression method. The 405 tumors were histologically classified as ordinary
      lipoma (n=324), intramuscular lipoma (n=29), and ALT/WDL (n=52). The level of
      agreement between the histologic diagnosis and the molecular diagnosis was high
      (96%) but pathologists showed a tendency to overestimate cytologic atypia and the
      diagnosis of ALT/WDL (precision, 79%; accuracy, 88%). Molecular assessment led to
      a major diagnostic reclassification in 18 tumors (4%). Eleven of the tumors
      histologically classified as ALT/WDL were reclassified as ordinary lipoma (n=5)
      and intramuscular lipoma (n=6); none of which recurred. Seven ordinary lipomas
      were reclassified as ALT/WDL, 6 of which were larger than 15 cm and deeply
      located; 2 recurred locally. After molecular data, the 5-year local recurrence
      rates for ordinary lipoma, intramuscular lipoma, and ALT/WDL were 1%, 12%, and
      44%, respectively. Multivariate analyses after molecular assessment showed tumor
      type and type of resection to be associated with the risk of local recurrence.
      Complementary molecular testing refines the histologic classification of
      lipomatous tumors and better estimates the impact of surgical procedures on the
      risk of local recurrence. Pathologists tend to overestimate the degree of
      cytologic atypia and the indiscriminate use of molecular testing should be
      avoided, especially for extremity-based tumors. Molecular testing should be
      considered for "relapsing lipomas," tumors with questionable cytologic atypia
      (even if widely excised), or for large lipomatous tumors (>15 cm) without
      diagnostic cytologic atypia.

PMID- 20679885
TI  - Epithelial-myoepithelial carcinoma with high grade transformation.
AB  - Epithelial-myoepithelial carcinoma (EMC) is a rare salivary gland tumor of
      presumed intercalated duct origin with a low risk of metastasis and mortality.
      Factors shown to affect behavior include positive margins, vascular invasion,
      necrosis, and myoepithelial anaplasia. The latter category and dedifferentiated
      EMCs have been separated on the basis of presumed myoepithelial versus ductal
      origin, respectively. Three additional cases of typical EMC with transition to
      high-grade carcinoma are presented. Two of the tumors were stained with CAM5.2,
      34betaE12, cytokeratin 14, p63, S100, calponin, smooth muscle actin, and muscle
      specific actin. All tumors showed a gradual transition to a high-grade carcinoma
      from an EMC, each composed of clear cells even in the high-grade regions. One
      case also showed a discrete area with ductal lumina and another had plasmacytoid
      morphology. Squamous differentiation was seen in all cases as well. A consistent
      immunostaining pattern was not noted. Areas with focal lumina were diffusely
      positive for CAM5.2 only. Areas with clear cells showed patchy S100 positivity
      only, whereas cytokeratin 14 and 34betaE12-stained squamous pearls. The case with
      plasmacytoid morphology was diffusely positive for p63. No immunoexpression was
      noted with smooth muscle actin, muscle-specific actin, or calponin. It was not
      possible to convincingly separate the high-grade component in these cases into
      ductal dedifferentiated EMC versus myoepithelial. Recently, there has been a move
      to abandon the term "dedifferentiation" in favor of "high-grade transformation"
      in other salivary gland malignancies. We report these 3 such cases, review the
      literature and propose that these lesions be regarded as "EMC with high-grade
      transformation."

PMID- 20679884
TI  - Xp11 translocation renal cell carcinoma (RCC): extended immunohistochemical
      profile emphasizing novel RCC markers.
AB  - Xp11 translocation renal cell carcinoma (RCC) harbor various TFE3 gene fusions,
      and are known to underexpress epithelial immunohistochemical (IHC) markers such
      as cytokeratin and EMA relative to usual adult type RCC; however, their profile
      in reference to other IHC markers that are differentially expressed in other
      subtypes of RCC has not been systematically assessed. Few therapeutic targets
      have been identified in these aggressive cancers. We created 2 tissue microarrays
      (TMA) containing five 1.4-mm cores from each of 21 Xp11 translocation RCC (all
      confirmed by TFE3 IHC, 6 further confirmed by genetics), 7 clear cell RCC
      (CCRCC), and 6 papillary RCC (PRCC). These TMA were labeled for a panel of IHC
      markers. In contrast to earlier published data, Xp11 translocation RCC frequently
      expressed renal transcription factors PAX8 (16/21 cases) and PAX2 (14/21 cases),
      whereas only 1 of 21 cases focally expressed MiTF and only 5 of 21 overexpressed
      p21. Although experimental data suggest otherwise, Xp11 translocation RCC did not
      express WT-1 (0/21 cases). Although 24% of Xp11 translocation RCC expressed HIF
      1alpha (like CCRCC), unlike CCRCC CA IX expression was characteristically only
      focal (mean 6% cell labeling) in Xp11 translocation RCC. Other markers
      preferentially expressed in CCRCC or PRCC, such as HIG-2, claudin 7, and EpCAM,
      yielded inconsistent results in Xp11 translocation RCC. Xp11 translocation RCC
      infrequently expressed Ksp-cadherin (3/21 cases) and c-kit (0/21 cases), markers
      frequently expressed in chromophobe RCC. Using an H-score that is the product of
      intensity and percentage labeling, Xp11 translocation RCC expressed higher levels
      of phosphorylated S6, a measure of mTOR pathway activation (mean H score=88),
      than did CCRCC (mean H score=54) or PRCC (mean H score=44). In conclusion, in
      contrast to prior reports, Xp11 translocation RCC usually express PAX2 and PAX8
      but do not usually express MiTF. Although they may express HIF-1alpha, they only
      focally express the downstream target CA IX. They inconsistently express markers
      associated with other RCC subtypes, further highlighting the lack of specificity
      of the latter markers. TFE3 and Cathepsin K remain the most sensitive and
      specific markers of these neoplasms. Elevated expression of phosphorylated S6 in
      Xp11 translocation RCC suggests the mTOR pathway as an attractive potential
      therapeutic target for these neoplasms.

PMID- 20679886
TI  - Monitoring long-term treatment with pegylated liposomal doxorubicin: how
      important is intensive cardiac follow-up?
AB  - Pegylated liposomal doxorubicin (PLD; Doxil or Caelyx) has been shown to be as
      effective as conventional doxorubicin, and to have a significantly better cardiac
      safety profile. The aim of this study was to assess the safety of delivering
      doses exceeding 700 mg/m of PLD to patients with solid tumors. A review of the
      medical records of 149 patients with a variety of solid tumors treated with PLD
      was performed. The findings in 12 patients who had reached or exceeded cumulative
      doses of 700 mg/m (median=1.071 mg/m, range 712-1856 mg/m) were reviewed. Changes
      in left ventricular ejection fraction (LVEF), and in clinical cardiac status were
      analyzed. The median age of the patients was 53.9 years and the median follow-up
      from the start of PLD treatment was 44.6 months. None of the 12 patients had
      clinical congestive heart failure secondary to cardiomyopathy. Seven of the 12
      patients underwent further assessment of LVEF by echocardiography or multiple
      gated acquisition scan, which revealed a stable or improved ejection fraction.PLD
      is cardiac safe for long-term treatment of metastatic solid tumors. Its maximal
      cumulative dose remains undefined. Frequent determinations of LVEF, as routinely
      done for other anthracyclines, do not appear to have any clinical value in
      patient follow-up. In metastatic patients with no evidence of cardiac risk
      factors, it may be sufficient to measure LVEF at baseline.

PMID- 20679887
TI  - Adjuvant cisplatin-based chemotherapy for resected NSCLC: one size fits all?
AB  - The standard of care for resected stage II - IIIA non-small-cell lung cancer
      includes adjuvant chemotherapy based on the results of randomized trials using
      cisplatin regimens. A recent meta-analysis (Lung Adjuvant Cisplatin Evaluation)
      showed no survival benefit for this modality in stage IB disease. Therefore, the
      role for stage IB disease remains controversial. The Lung Adjuvant Cisplatin
      Evaluation meta-analysis, which is based on pooled data of five randomized
      trials, has shown a 5.3% absolute survival benefit at 5 years. However, long-term
      results of the International Adjuvant Lung Cancer Trial evaluating adjuvant
      cisplatin-based chemotherapy in resected non-small-cell lung cancer indicated a
      possible late adjuvant chemotherapy-related over-mortality. Tumor stage currently
      is the benchmark standard use for identifying patients who would benefit from
      adjuvant treatment. In the knowledge of late adjuvant chemotherapy-related over
      mortality it is therefore critical to identify subsets of patients who would or
      would never benefit from adjuvant cisplatin. This review will discuss the extent
      to which individualized adjuvant treatment can be provided.

PMID- 20679888
TI  - Statistical identification of predictors for peripheral neuropathy associated
      with administration of bortezomib, taxanes, oxaliplatin or vincristine using
      ordered logistic regression analysis.
AB  - Chemotherapy-induced peripheral neuropathy (CIPN) is a major drug-induced adverse
      reaction that becomes a dose-limiting toxicity. However, effective strategies for
      preventing or treating CIPN are lacking. Accordingly, this study aimed to
      statistically identify predictors for CIPN. Retrospective analysis was carried
      out for 190 patients who had been treated with bortezomib (n=28), taxanes
      (paclitaxel or docetaxel; n=58), oxaliplatin (n=52) or vincristine (n=52) at our
      hospital between April 2005 and December 2008. The severity of CIPN was assessed
      at the time of chemotherapy completion, graded as grade 0-5 in accordance with
      the National Cancer Institute Common Terminology Criteria for Adverse Events
      v3.0. Multivariate ordered logistic regression analysis was used to investigate
      predictors for CIPN. Predictors for CIPN in patients that were administered
      bortezomib were no co-administration of dexamethasone [odds ratio (OR), 0.455;
      confidence interval (CI), 0.208-0.955; P=0.0376] and sex (male) (OR, 3.035; CI,
      1.356-6.793; P=0.0069). For taxanes (paclitaxel or docetaxel), the predictor for
      CIPN was a large number of chemotherapy cycles (OR, 2.379; CI, 1.035-5.466;
      P=0.0412). For oxaliplatin, the predictors for CIPN were a large number of
      chemotherapy cycles (OR, 3.089; CI, 1.598-5.972; P=0.0008) and no co
      administration of non-steroidal anti-inflammatory drugs (OR, 0.393; CI, 0.197
      0.785; P=0.0082). For vincristine, predictors for CIPN were a large number of
      chemotherapy cycles (OR, 6.015; CI, 1.880-19.248; P=0.0025) and co-administration
      of an analgesic adjuvant (OR, 3.907; CI, 1.383-11.031; P=0.0101). In conclusion,
      our study indicates that CIPN will be alleviated by the co-administration of
      dexamethasone with bortezomib and non-steroidal anti-inflammatory drugs with
      oxaliplatin.

PMID- 20679889
TI  - p53 gene therapy for pulmonary metastasis tumor from hepatocellular carcinoma.
AB  - The objective of this study is to explore the safety, efficacy, and
      administration method of the recombinant adenovirus p53 gene (rAd-p53, or
      gendicine) in the treatment of pulmonary metastasis tumor from advanced
      hepatocellular carcinoma (HCC). Pulmonary metastasis tumors from HCC in 20
      patients were treated by using transcatheter bronchial arterial gendicine
      infusion combined with transcatheter arterial embolization and intratumor
      injection of gendicine if the maximal diameter of a metastatic tumor is greater
      than or equal to 3 cm. Three patients received the combined therapy three times,
      seven received it twice, and ten received it once. Eighteen patients were
      followed for 2-12 months after treatment and two patients were lost to follow-up.
      Spiral computed tomography was performed during follow-up visits to monitor tumor
      progress. Lung metastasis tumor disappeared in four patients and the tumor size
      decreased in six patients, remained unchanged in five, and increased in three
      patients. Overall, the clinical symptoms were alleviated in 16 patients (88.9%)
      and were exacerbated in two patients. New metastatic lesions were found in eight
      patients. There were no serious adverse events except for self-limited fever (38
      degrees C-39.5 degrees C), which was found in 16 patients. Transcatheter
      bronchial arterial gendicine infusion combined with transcatheter arterial
      embolization, with or without intratumor injection of gendicine, is a safe,
      effective therapy for the treatment of pulmonary metastasis tumor from HCC.

PMID- 20679890
TI  - Regulation of apoptosis-associated genes by histone deacetylase inhibitors:
      implications in cancer therapy.
AB  - Anomalous gene regulation, dictated by epigenetic modifications, is a universal
      characteristic of cancer cells. Histone deacetylases (HDACs) are an important
      class of enzymes that influence gene expression by the removal of acetyl groups
      from histones leading to chromatin remodeling and transcriptional suppression of
      key apoptosis and cell cycle regulatory genes. Histone deacetylase inhibitors
      (HDACis) are a novel category of anticancer pharmacological agents developed to
      counter the actions of HDACs, thus, inducing an array of cellular consequences,
      such as apoptosis, cell cycle arrest, generation of reactive oxygen species,
      inhibition of angiogenesis, and autophagy. Suberoylanilide hydroxamic acid (SAHA,
      Zolinza, Vorinostat), is currently the only Food and Drug Administration-approved
      HDACi for the treatment of cutaneous T-cell lymphoma. SAHA and other HDACis have
      shown selective toxicity toward malignant cells while sparing the surrounding
      normal cells. In addition to this specificity, their regulation of apoptosis
      associated genes and the synergistic augmentation of apoptotic events when used
      simultaneously with other anticancer agents such as conventional chemotherapies,
      radiation, inhibitors of DNA methylation, and proteasome inhibitors make HDACis
      potential novel arsenals in the battle against cancer. Herein I review epigenetic
      modifications, discuss the various mechanisms of HDACi-induced effects, in
      particular modulation of expression of apoptosis-associated gene products, and
      highlight SAHA and its antitumor functions.

PMID- 20679891
TI  - Brain-derived neurotrophic factor in traumatic brain injury, post-traumatic
      stress disorder, and their comorbid conditions: role in pathogenesis and
      treatment.
AB  - As US military service members return from the wars in Iraq and Afghanistan with
      elevated rates of traumatic brain injury (TBI) and post-traumatic stress disorder
      (PTSD), attention has been increasingly focused on TBI/PTSD comorbidity, its
      neurobiological mechanisms, and novel and effective treatment approaches. TBI and
      PTSD, and their comorbid conditions, present with a spectrum of common clinical
      features such as sleep disturbance, depression, anxiety, irritability, difficulty
      in concentrating, fatigue, suicidality, chronic pain, and alterations in arousal.
      These TBI and PTSD disorders are also thought to be characterized by overlapping
      neural mechanisms. Both conditions are associated with changes in hippocampal,
      prefrontal cortical, and limbic region function because of alterations in
      synaptogenesis, dendritic remodeling, and neurogenesis. Neural changes in TBI and
      PTSD result from pathophysiological disturbances in metabolic, cytotoxic,
      inflammatory, and apoptic processes, amongst other mechanisms. Neurotrophins have
      well-established actions in regulating cell growth and survival, differentiation,
      apoptosis, and cytoskeleton restructuring. A body of research indicates that
      dysregulation of neural brain-derived neurotrophic factor (BDNF) is found in
      conditions of TBI and PTSD. Induction of BDNF and activation of its intracellular
      receptors can produce neural regeneration, reconnection, and dendritic sprouting,
      and can improve synaptic efficacy. In this review, we consider treatment
      approaches that enhance BDNF-related signaling and have the potential to restore
      neural connectivity. Such treatment approaches could facilitate neuroplastic
      changes that lead to adaptive neural repair and reverse cognitive and emotional
      deficits in both TBI and PTSD.

PMID- 20679892
TI  - Conjugated equine estrogen, with medroxyprogesterone acetate, enhances formation
      of 5alpha-reduced progestogens and reduces anxiety-like behavior of middle-aged
      rats.
AB  - The mechanisms by which progestogens influence affective behaviors in females are
      poorly understood despite clear changes in mood/affect that are associated with
      their decline during menopause. Conjugated equine estrogens (CEE), with or
      without medroxyprogesterone acetate (MPA), are commonly prescribed hormone
      replacement, but there is heterogeneity in responses to these pharmacotherapies.
      One way in which these compounds differ is in their capacity to potentiate
      metabolism of progesterone to its 5alpha-reduced products, dihydroprogesterone
      and 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP). This study investigated
      whether responses to CEE and MPA may be related to the capacity to metabolize
      progesterone. Middle-aged female rats that had maintained reproductive status, or
      those that had a decline, were administered vehicle, CEE and/or MPA. Effects on
      anxiety-like (open field, elevated plus maze) and social behaviors (social
      interaction test), and plasma and hippocampus steroid levels were determined. We
      hypothesized that CEE, but not MPA, would decrease anxiety-like behavior
      coincident with increased hippocampal metabolism of progesterone. CEE, or
      CEE+MPA, increased central entries in the open field and time spent on the open
      arms of the plus maze, but did not alter social interaction of rats that had
      maintained reproductive status. CEE and/or CEE+MPA increased E2 and 3alpha,5alpha
      THP in plasma and/or hippocampus of rats, but MPA increased levels of
      dihydroprogesterone in the hippocampus of rats with declining reproductive
      status. Simple regressions showed that hippocampus 3alpha,5alpha-THP levels
      accounted for a significant proportion of the variance in anxiety-like behavior.
      Therefore, effects of CEE to reduce anxiety-like behavior of middle-aged rats may
      be owing, in part, to its capacity to enhance levels of 3alpha,5alpha-THP in the
      hippocampus.

PMID- 20679893
TI  - Tianeptine reduces morphine antinociceptive tolerance and physical dependence.
AB  - Long-term use of morphine can cause neuronal dystrophic changes in specific areas
      of the brain. These changes may underlie the mechanism for developing morphine
      antinociceptive tolerance and physical dependence. We evaluated the effect of
      tianeptine, an antidepressant with prominent neuroprotective and neuroplastic
      properties, on the development of morphine antinociceptive tolerance and physical
      dependence. Male C57BL/6 mice were rendered tolerant to or dependent on morphine
      by subcutaneously injecting them with morphine (10 mg/kg) and intraperitoneally
      with saline or tianeptine (1, 3, or 5 mg/kg) twice daily for 6 days. The mice
      were given a daily tail-flick test 1 h after the first morphine injection to
      evaluate the development of their tolerance to morphine antinociception. To
      evaluate their physical dependence on morphine, 3 h after the final morphine
      injection on day 6, naloxone-HCl-precipitated (2 mg/kg, intraperitoneally)
      withdrawal symptoms were counted for 30 min, and body weight was checked 1 h
      after the naloxone injection. Tianeptine per se produced no antinociception,
      neither did it modify the antinociception produced by morphine, nor did it evoke
      the behavioral responses different from those in the saline controls. The
      combination of tianeptine with morphine significantly reduced the development of
      morphine antinociceptive tolerance and suppressed the incidence of naloxone
      precipitated withdrawal symptoms. We conclude that tianeptine is an effective
      inhibitor of morphine-induced antinociceptive tolerance and physical dependence
      in mice. Our results would imply that comedication with tianeptine and morphine
      might benefit those who need long-term morphine treatment.

PMID- 20679894
TI  - The role of heart-type fatty acid-binding protein in predicting properties of
      coronary atherosclerosis in patients with acute coronary syndrome.
AB  - INTRODUCTION: Fatty acid-binding protein (FABP) is an independent predictor of
      cardiac events. However, the relation between increasing FABP and coronary
      atherosclerosis is unknown. We have investigated the relation between FABP and
      angiographic properties of coronary atherosclerosis in patients with acute
      coronary syndrome (ACS). METHODS: The study population consisted of 93 patients
      with ACS (mean age: 56+/-10 years). Patients presenting to the emergency
      department within 2 h after onset of anginal symptoms were enrolled in the study.
      FABP was measured at second, fourth and sixth hours of chest pain. Cut-off FABP
      was accepted as 1.9 ng/ml. Coronary atherosclerosis was assessed with diseased
      vessel number (>=50 and >=70% luminal narrowing), Gensini and extent scores.
      RESULTS: Median FABP-2 was 2.9 ng/ml (interquartile range: 1.6-10.4). Peak FABP
      was measured at fourth hour [median: 35.0 ng/ml (interquartile range: 2-77)].
      There was a nonsignificant relation between angiographic findings and FABP-2. At
      fourth hour, Gensini, extent score and diseased vessel number were significantly
      higher above the cut-off level of FABP-4 (Gensini score: 3.7+/-3.4 vs. 6.2+/-3.4,
      P=0.005; extent score: 11.1+/-10 vs. 22.3+/-19.2, P=0.007; diseased vessel: 0.7+/
      0.6 vs. 1.6+/-1.0, P=0.003, respectively). The sensitivity of FABP-2 for at least
      50% lesion was 70%. The highest sensitivity was obtained at fourth hour (85% for
      >=50% and 88% for >=70% lesions). The sensitivity and positive predictive values
      for revascularization were 70 and 77% for FABP-2, 89 and 80% for FABP-4 and 89
      and 81% for FABP-6. CONCLUSION: FABP levels are closely related with angiographic
      properties of patients with ACS. FABP may be an early and important marker for
      predicting the coronary anatomy and decision of treatment.

PMID- 20679895
TI  - Opportunistic prostate-specific antigen screening in Italy: 6 years of monitoring
      from the Italian general practice database.
AB  - The practice of prostate-specific antigen (PSA) screening has been increasing in
      Italy despite uncertain scientific evidence and contrary recommendations from
      most scientific societies. In 2002, a survey of PSA screening diffusion among
      general practices was performed, looking for screening frequency and age pattern
      of screened individuals. The objective of this study was to assess whether the
      features of PSA screening did change after 6 years in the same considered
      setting. Using the data obtained from 500 Italian general practitioners providing
      information to the Health Search/CSD Patient database, we selected, for the study
      purpose 351,091 male individuals. We assumed PSA prescriptions performed during
      2005-2008 in individuals without prostate cancer, or benign prostate disease, or
      urological symptoms history to have a screening purpose. Screening frequency was
      analyzed in the overall series, by year and by patient's age. Exposure to PSA
      screening (at least on PSA test in the considered period) of males aged over 50
      years raised from 31.4% (confidence interval 95% 31.08-31.70%) during 2002 to
      46.4% (confidence interval 95% 46.19-46.68%) during 2008. The highest yearly
      exposure to PSA screening (55%) and the highest frequency of repeat testing was
      observed in the 70-79 age range. PSA screening practice has continued to increase
      in Italy and is often performed in elderly people without any scientific
      rationale.

PMID- 20679897
TI  - Atraumatic splenic rupture: a 6-year case series.
AB  - Atraumatic splenic rupture is an uncommon but poorly defined clinical condition.
      Its diagnosis may be missed or delayed because of low clinical suspicion,
      especially in the absence of trauma. The primary aim of this study was to
      describe the experience with atraumatic splenic rupture in a district general
      hospital. Over a 6-year period (2004-2010), seven patients were identified,
      producing an incidence of 1.2/year. Computed tomography confirmed the diagnosis
      preoperatively in all the cases where it was performed (n=5). All patients
      required total splenectomy; indications included peritonitis, hypovolaemic shock
      and failed conservative treatment. Five splenectomies were performed within 24 h
      of admission. In four cases, no pathological abnormality was identified
      (atraumatic-idiopathic); abnormal pathologies (atraumatic-pathological) in the
      remaining three were amyloidosis, lymphoma and focal thrombosis. A high index of
      suspicion should be maintained by emergency physicians and surgeons during
      initial evaluation of these patients. Computed tomography scan facilitates the
      diagnosis and early total splenectomy is often needed.

PMID- 20679896
TI  - Alcohol consumption and cancers of the oral cavity and pharynx from 1988 to 2009:
      an update.
AB  - Evidence for the human carcinogenic effects of alcohol consumption on the risk of
      cancers of the oral cavity and pharynx has been considered sufficient in the
      International Agency for Research on Cancer Monograph 44 on alcohol and cancer in
      1988. We evaluated human carcinogenic evidence related to the risk of oral and
      pharyngeal cancers based on cohort and case-control studies published from 1988
      to 2009. A large body of evidence from epidemiological studies of different
      designs and conducted in different populations has consistently supported the
      fact that alcohol consumption is strongly associated with an increase in the risk
      of oral and pharyngeal cancers. The relative risks are 3.2-9.2 for more than 60
      g/day (or more than four drinks/day) when adjusted for tobacco smoking and other
      potential confounders. A strong dose-response effect on the intensity of alcohol
      use is reported in most of the studies. However, no apparent association is
      observed for the duration of alcohol use. Compared with current alcoholics, a
      decreased risk of approximately 10 to 15 years is associated with alcohol
      cessation. Similar associations have been observed among nonsmokers in over 20
      studies. In general, the dominant type of alcohol consumption in each population
      is associated with the greatest increase in risk. A large number of studies on
      joint exposure to alcohol and tobacco consumption show a greater than
      multiplicative synergistic effect.

PMID- 20679898
TI  - Chronic health needs immediately after natural disasters in middle-income
      countries: the case of the 2008 Sichuan, China earthquake.
AB  - Few studies have focused on chronic health needs immediately after natural
      disasters in middle-income countries. This study examines chronic medical needs
      during the acute phase after the 2008 Sichuan earthquake. A descriptive, cross
      sectional study was conducted in an emergency triage clinic in Sichuan, China.
      Information on physical, social, and public health preparedness was collected in
      predesigned templates. Descriptive and Pearson's chi association analyses were
      conducted. One hundred and eighty-two evacuees were received at the triage site.
      Of these, 54% required trauma treatment and 77% of evacuated patients who
      required care had underlying chronic medical conditions. Tetanus immunizations
      and the possession of chronic health medication were low, particularly among
      older patients. Chronic health needs constituted a significant proportion of
      emergency care during the acute phase in the study population. Effective post
      disaster assistance requires attention to demographic and epidemiological
      population profiles.

PMID- 20679899
TI  - Acute severe asthma: performance of ventilator at simulated altitude.
AB  - OBJECTIVE: Exacerbation of asthma can be seen during air transport. Severe
      patients, not responding to conventional therapy, require ventilator support. We
      evaluated the performance of two transport ventilators, built with turbine
      technology, the T-birdVSO2 and the LTV-1000, for use during aeromedical
      evacuation of acute severe asthma. We have assessed the ability of both the
      ventilators to deliver to an acute severe asthma model a tidal volume (Vt) set at
      different simulated altitudes, by changing the ambient air pressure. METHODS: The
      simulated cabin altitudes were 1500, 2500, and 3000 m (decompression chamber). Vt
      was set at 700 and 400 ml in an acute severe asthma lung model. Comparisons of
      the preset with the actual measured values were accomplished using a t-test.
      RESULTS: Comparisons between the actual delivered Vt and set Vt showed a
      significant difference starting at 1500 m for both the ventilators. The T
      birdVSO2 showed a decrease in the volume delivered, with a negative variation of
      more than 10% compared with the Vt set. The LTV-1000 showed mostly an increase in
      the volume delivered. The delivered Vt remained within 10% of the set Vt.
      CONCLUSION: The accuracy of Vt delivery was superior with the LTV-1000 than with
      the T-birdVSO2, but the higher delivered Vt of the LTV-1000 are likely to be more
      harmful than lower delivered Vt of the T-birdVSO2.

PMID- 20679900
TI  - Interrater agreement: a comparison between two emergency department triage
      scales.
AB  - OBJECTIVE: The aim was to elucidate if, by strictly applying the Adaptive Process
      Triage (ADAPT) scale, the interrater agreement increased among the participating
      registered nurses (RNs) than when triaging according to the older scale, which
      allowed subjective interpretations of signs and symptoms. METHODS: Nineteen
      patient scenarios were triaged in 2006 by 45 RNs using the previous triage scale,
      and in 2008 by 30 RNs using ADAPT. RESULTS: There was no significant difference
      (P=0.65) between the two triage scales with regard to level of overall exact
      agreement (kappa value 0.529 vs. 0.472). The same triage level was more often
      chosen when using the ADAPT system as compared to the earlier triage scale and
      dispersion across the triage levels was also reduced when using ADAPT. Eight
      (42%) of the patient scenarios were triaged as both unstable and stable by ADAPT,
      and 11 (58%) when the older scale was applied. Fourteen (74%) of the scenarios
      could not be allocated to a defined triage level by ADAPT. Five main reasons for
      such triage decisions were identified. CONCLUSION: Both the triage scales showed
      moderate overall agreements, while dispersion of triage decisions across several
      triage levels declined when ADAPT was used. Although the algorithm for acuity
      allocation by ADAPT seemed well defined, many patient scenarios were triaged as
      both unstable and stable and thus allocated to various triage levels. If ADAPT is
      to function as a safe triage tool with low interrater variability, further
      revision of the triage algorithms is needed.

PMID- 20679901
TI  - Decreased postural balance in multiple sclerosis patients with low disability.
AB  - To evaluate balance in women with multiple sclerosis (MS) who have low disability
      and minimal clinical impairments as measured by the Expanded Disability Status
      Scale (EDSS), and compare them with healthy age-matched controls. Patients were
      aged between 18 and 64 years; 67 individuals with MS (MU=44.0 +/- 1.2 years) and
      45 healthy controls (MU=40.4 +/- 2.4 years). All patients had an EDSS score of
      3.5 or below. Both the groups underwent a series of balance measures using the
      NeuroCom Balance Master. The mean EDSS for the MS group was 1.8. For balance,
      there was a significant difference between the two groups, with the MS group
      performing worse on the modified clinical test for sensory integration of balance
      measures standing on a foam surface with eyes closed (P<0.01). A significant
      difference was also found for the unilateral stance with eyes closed and eyes
      open, and the tandem walk, with the MS group showing significantly more sway
      during those tests (P<0.01). The MS group did significantly worse when compared
      with the healthy age-matched controls on the balance measures, indicating greater
      postural instability despite the low disability measured by EDSS.

PMID- 20679902
TI  - Perceived participation, experiences from persons with spinal cord injury in
      their transition period from hospital to home.
AB  - It is suggested that participation should be achieved at the end of the
      rehabilitation process. However, there is a lack of consensus on the definition,
      the conceptualization and the measurement of participation. This study aims to
      add to the existing body of knowledge of participation by exploring the 'person
      perceived participation' in individuals with spinal cord injury (SCI). On the
      basis of the 'grounded theory' approach, in-depth, semistructured interviews were
      conducted with 11 SCI patients from a rehabilitation cohort in their transition
      period from hospital to home, to gain an insider perspective on the concept of
      participation. Results identified three different categories of participation:
      social participation, occupational participation and socio occupational
      participation. The participants conceptualize participation as a set of values,
      including experiencing free choice to perform activities, performing according to
      the person's identity, experiencing personal growth, belonging by experiencing
      trust and security, feeling validated, having a sense of control, experiencing a
      sense of importance and finding equal identities. In conclusion, from a client
      perspective, participation is a complex,multidimensional construct and can be
      considered asa dyad between the individual's social interactions and his specific
      activities performed. Participation was not experienced by the SCI patients as an
      objective way of performing activities within a societal context or as
      frequencies of activities performed, but rather as an internal process of
      negotiation that seemed to be based on balancing personal and societal values.

PMID- 20679903
TI  - Clinical utility of colonic and anorectal manometry in chronic constipation.
AB  - Constipation is one of the most common digestive problems in North America with
      significant psychosocioeconomic implications. It is caused by either a primary
      disorder of colonic and anorectal function or by many secondary conditions such
      as constipating drugs, metabolic disorders and other colorectal problems. Given
      the heterogeneity of problems that cause constipation, defining the underlying
      pathophysiology is increasingly being recognized as a key step toward optimal
      management. Colonic manometry with sensation and tone assessment (barostat) and
      anorectal manometry with rectal sensation and compliance assessment and balloon
      expulsion test can provide a comprehensive evaluation of colonic and anorectal
      sensorimotor function and facilitate a diagnosis of slow transit constipation,
      dyssynergic defecation or irritable bowel syndrome, or an overlap of these
      disorders. This review provides a critical appraisal of the role of manometric
      techniques toward augmenting our understanding of colonic and anorectal
      physiology, both in health and constipation and discussing their clinical utility
      in the diagnosis and management of chronic constipation.

PMID- 20679904
TI  - A new PPI, ilaprazole compared with omeprazole in the treatment of duodenal
      ulcer: a randomized double-blind multicenter trial.
AB  - GOALS: To investigate the efficacy and safety of a new proton pump inhibitor
      (PPI), ilaprazole (IY-81149) in the treatment of duodenal ulcers and provide some
      characteristics of the dose-response relationship for later studies. BACKGROUND:
      PPIs have been used therapeutically for many years, and shown great efficacy in
      accelerating ulcer healing. Currently researches are focused on more potent PPIs.
      Some preclinical studies have shown that ilaprazole might be such a new
      substitute. STUDY: 235 patients with at least 1 endoscopically diagnosed active
      duodenal ulcer were enrolled in a randomized trial. Patients were randomized into
      4 groups (5, 10, and 20 mg/d ilaprazole, with 20 mg/d omeprazole as positive
      control) and treated for up to 4 weeks. Forty patients accepted continuous 24
      hour pH measurements after the fifth dose. The primary endpoint was ulcer healing
      rate at week 4. RESULTS: The efficacy analyses were based on 235 patients. At
      week 4, 86.4%, 93.1%, 86.4%, and 89.8% patients treated with 5 mg ilaprazole, 10
      mg ilaprazole, 20 mg ilaprazole, and 20 mg omeprazole once daily, respectively
      had ulcers healed (P=0.59). The majority of patients (>70%) became asymptomatic
      after 4 weeks treatment. Both drugs with stipulated dosages exhibited similar
      efficacy and safety profiles. Gastric acid suppression increased with increasing
      dose of ilaprazole in pH study. CONCLUSIONS: Ilaprazole is as tolerable, safe,
      and efficacious as omeprazole in the treatment of duodenal ulcers, especially at
      a lower dose (10 mg/d ilaprazole vs. 20 mg/d omeprazole). (ClinicalTrials.gov ID:
      NCT00953381).

PMID- 20679905
TI  - Cyclosporine is safe and effective in patients with severe ulcerative colitis.
AB  - BACKGROUND: Cyclosporine (CSA) is effective in the short-term for severe, steroid
      refractory ulcerative colitis; but its use has been limited by concerns about
      safety and colectomy-sparing rates. The aim of this study was to assess the long
      term colectomy-sparing effects and safety of CSA in patients hospitalized for
      ulcerative colitis. METHODS: Review of the patients who underwent intravenous CSA
      for ulcerative colitis between 1989 and 2003. RESULTS: A total of 71 patients
      with severe ulcerative colitis were treated with IV CSA. The median length of
      follow-up was 1.5 years (mean=3 y) (range 1 mo to 14 y) (IQR 0.6 to 4.6). Eighty
      five percent (60/71) of patients responded to IV CSA and were discharged on oral
      CSA. Of these 60 patients, 26 were transitioned from CSA to 6MP. Of the 26
      patients who were transitioned from CSA to 6MP, only 1 patient (4%) ultimately
      required colectomy; whereas colectomy was carried out in 76% (26/34) of the
      patients who were not transitioned from CSA to 6MP. Only concomitant 6MP therapy
      was associated with a reduced risk of colectomy (OR 0.01, 95% CI 0.001, 0.09,
      P<0.0001) on long-term follow-up in this group. Cumulative colectomy rates for
      the entire cohort were 39% (28/71) at 1 year, 42% (30/71) at 2 years, and 46%
      (33/71) at 5 years. Side effects were noted in two-thirds of the patients, the
      majority of which were mild. CONCLUSION: CSA is an effective therapy for severe
      ulcerative colitis. Long-term efficacy is improved with transition to 6MP.
      Adverse events with CSA are frequent, but most are mild.

PMID- 20679906
TI  - Comparison of the impact of wireless versus catheter-based pH-metry on daily
      activities and study-related symptoms.
AB  - AIMS: To evaluate the variation in tolerance to wireless pH-metry compared with
      catheter-based pH-metry, and to determine clinical characteristics that might
      predict reduced tolerance to wireless pH-metry. METHODS: Consecutive outpatients
      (n=341) completing wireless (n=234) or catheter-based pH-metry (n=106) were
      evaluated. All patients completed the pH-Metry Impact Scale and the pH-Metry
      Symptoms Scale to assess the impact of the pH-metry on activities of daily living
      and pH-metry associated changes in study-related symptoms. All data are presented
      as mean (SD) or odds ratios (95% confidence interval). RESULTS: The impact of pH
      metry on activities of daily living were modest, but wireless pH-metry had less
      impact than catheter-based pH-metry (P=0.01). A sense of foreign body in the
      chest, chest discomfort, and chest pain were reported more frequently during
      wireless pH-metry. Difficulty swallowing and painful swallowing were more common
      during catheter-based pH-metry. Noncardiac chest pain was associated with
      increased symptom severity. Patients with poor tolerance were twice as likely to
      have a diagnosis of noncardiac chest pain (odds ratio=2. 53; 95% confidence
      interval, 1.4-4.6). CONCLUSIONS: Wireless pH-metry has less of an impact on
      activities of daily living but is not associated with fewer study-related
      symptoms compared with catheter-based pH-metry. The prevalence of specific study
      related symptoms does differ between the 2 groups and noncardiac chest pain seems
      to be the primary risk factor for more severe study-related symptoms and reduced
      tolerance for wireless pH-metry. This information may be useful in helping to
      decide which patients should undergo the wireless pH-metry or receive additional
      counseling on procedural expectations.

PMID- 20679907
TI  - Patients with IBD are exposed to high levels of ionizing radiation through CT
      scan diagnostic imaging: a five-year study.
AB  - GOALS: The objective of this study was to assess the total effective dose of
      ionizing radiation from abdominal diagnostic imaging in patients with
      inflammatory bowel disease (IBD) over a 5-year period. BACKGROUND: Radiation
      exposure from diagnostic imaging is becoming increasingly common in IBD patients,
      in part due the availability of computed tomography (CT). Increased risk of
      malignancy has been associated with radiation exposure. STUDY: This is a
      retrospective chart review. A university-based gastroenterology database was
      searched for patients with a diagnosis of Crohn's disease (CD) or ulcerative
      colitis (UC) seen between 2003 and 2008. The cumulative ionizing radiation
      exposure, expressed in milli-Sieverts (mSv), was then calculated from standard
      tables and by counting the number of abdominal imaging studies. RESULTS: Patients
      with CD had higher cumulative radiation exposure from diagnostic imaging than
      patients with UC (14.3 +/- 1.45 mSv/5-y period vs. 5.9 +/- 0.81 mSv/5-y period,
      P=0.00003). Three-quarters of the radiation exposure in both CD and UC was from
      CT scans. Thirty-four percent (127 of 373) of CD patients had CT scans, compared
      with just 20% (37 of 182) of UC patients. Importantly, 7% of CD patients were
      exposed to high levels of radiation (>50 mSv/5 y), in contrast to none of the UC
      patients. CONCLUSIONS: Patients with IBD, and especially CD patients, undergo
      frequent diagnostic imaging and thus significant exposure to ionizing radiation.
      This radiation exposure reaches high levels in 7% of CD patients, mainly from CT
      scanning. Efforts should be made to minimize the radiation exposure from
      diagnostic imaging by reducing either the number of studies or radiation dose in
      modalities with ionizing radiation.

PMID- 20679908
TI  - The thickness of melanomas has decreased in central Italy, but only for thin
      melanomas, while thick melanomas are as thick as in the past.
AB  - The objective of this study was to evaluate the time trend of melanoma thickness
      in a population-based case series. All invasive (n=2862) and in-situ (n=605)
      cutaneous melanoma incident cases diagnosed in 1985-2004 were retrieved from the
      Tuscany Cancer Registry, central Italy. Standardized (European population)
      incidence rates were computed for four periods: 1985-1989, 1990-1994, 1995-1999,
      2000-2004, and for Breslow thickness classes (< or =1, 1.01-2.00, >2 mm). The
      annual percent change (APC) of the standardized rates was computed. Thickness was
      evaluated on the basis of sex, age, morphology type, site and period of time.
      Median thickness was evaluated by means of a nonparametric K-sample test. The
      incidence rate of melanoma rose significantly for both invasive (APC=+5.1%) and
      in-situ lesions (APC=+11.1). The sex distribution of patients with invasive
      melanoma did not change over time (mean male/female ratio 0.95). The mean age at
      diagnosis did not change (57.2 years; SD=17.2 years). From 1985-1989 to 2000-2004
      the median value of thickness decreased from 1.68 to 0.8 mm (P<0.001). Within the
      Breslow categories the median value of thickness decreased significantly for thin
      melanomas (< or =1 mm) but not for intermediate (1.01-2.00) or for thick
      melanomas (>2 mm). Among the most common melanoma types, the median thickness
      decreased for superficial spreading melanomas but not for nodular melanomas. Over
      time, the incidence of melanoma has increased notably and the median thickness
      has decreased. However, median thickness has decreased only among thin melanomas,
      whereas it has not changed for thick melanomas, most of which are of the nodular
      type.

PMID- 20679909
TI  - An inexpensive, specific and highly sensitive protocol to detect the BrafV600E
      mutation in melanoma tumor biopsies and blood.
AB  - The Braf(V600E) mutation has been detected in patients with metastatic melanoma,
      colon, thyroid and other cancers. Recent studies suggested that tumors with this
      mutation are especially sensitive to Braf inhibitors, hence the need to reliably
      determine the Braf status of tumor specimens. The present technologies used to
      screen for this mutation fail to address the problems associated with
      infiltrating stromal and immune cells bearing wild-type Braf alleles and thus may
      fail to detect the presence of mutant Braf(V600E) tumors. We have developed a
      rapid, inexpensive method that reduces the contamination of wild-type Braf
      sequences from tumor biopsies. The protocol involves a series of PCR
      amplifications and restriction digestions that take advantage of unique features
      of both wild type and mutant Braf RNA at position 600. Using this protocol,
      mutant Braf can be detected in RNA from mixed populations with as few as 0.1%
      Braf(V600E) mutant cells.

PMID- 20679911
TI  - Graded contribution of hippocampus to multifeature binding across temporal delay.
AB  - It is well accepted that all the elements of an episode are combined together by
      the hippocampus to form an episodic representation. In this study, we further
      investigated whether the activation pattern of the hippocampus during
      multifeatural episodic encoding with temporal discontinuities varies with
      recollective detail in a graded way. Specifically, in the present functional
      magnetic resonance imaging study, we manipulated two associative features, color
      and size, and presented the features and the item sequentially. Right hippocampal
      activation increased with the number of features successfully bound to the item,
      supporting a graded role of hippocampal activation in bridging temporal
      discontinuities for integrating multiple episodic features.

PMID- 20679910
TI  - Metastasis in an orthotopic murine model of melanoma is independent of RAS/RAF
      mutation.
AB  - Melanoma is the most lethal skin tumor in large part because of a propensity for
      early metastasis. Good models of this most clinically relevant feature of
      melanoma are lacking. Here, we report the development of an in-vivo model of
      metastasis that relies on orthotopic injection of green fluorescent protein
      tagged lines in immunodeficient mice, serial intravital imaging of tumor
      progression, and quantification of distant spread by two-photon laser scanning
      microscopy, immunohistochemistry, and real-time PCR analysis. Using this system,
      we report an assessment of the in-vivo growth and metastatic properties of 11
      well-characterized human melanoma cell lines. A subset of lines showed rapid in
      vivo growth with invasion of host vasculature and distant seeding of viscera in
      this system. The ability to form metastasis in vivo did not correlate with three
      dimensional collagen invasion in vitro. Surprisingly, similar lines in terms of
      molecular genetic events differed markedly in their propensity to metastasize to
      distant organs such as brain and lung. In particular, two lines harboring B-RAF
      mutation and high levels of phosphorylated ERK and AKT were reproducibly unable
      to form tumors after orthotopic injection. Similarly, two previously identified
      RAS/RAF wildtype 'epithelial like' lines that do not have elevated phosphorylated
      ERK and AKT or express TWIST1 mRNA still showed a pronounced ability for
      orthotopic growth and metastatic spread. All the metastatic cell lines in this
      model showed increased NEDD9 expression, but NEDD9 lentiviral overexpression did
      not convey a metastatic phenotype on nonmetastatic cells. These data suggest that
      melanoma metastasis is a molecularly heterogeneous process that may not require
      epithelial-to-mesenchymal transition or ERK activation, although both may
      facilitate the process.

PMID- 20679912
TI  - Arterial bypass surgery using a spontaneously formed "bonnet" superficial
      temporal artery in a patient with symptomatic common carotid artery occlusion:
      case report.
AB  - BACKGROUND: Common carotid artery (CCA) occlusive disease may cause hemodynamic
      cerebral ischemia resulting in the development of ischemic symptoms. The blood
      flow in the superficial temporal artery (STA) ipsilateral to the occluded CCA is
      usually poor, which limits its use as a donor artery for extracranial
      intracranial arterial bypass surgery. CLINICAL PRESENTATION: Despite antiplatelet
      therapy, recurrent transient ischemic attacks manifesting as motor aphasia
      developed in a 72-year-old man. Neuroradiological imaging revealed misery
      perfusion in the bilateral cerebral hemispheres caused by left CCA occlusion and
      right internal carotid artery occlusion. Blood flow from the STA contralateral to
      the occluded CCA perfused the ipsilateral STA over the midline in a retrograde
      fashion. INTERVENTION: After confirming the direction and the pressure of the
      blood flow in the spontaneously formed "bonnet" STA, the STA was anastomosed to a
      cortical artery in the symptomatic frontal lobe so that blood flow in the
      ipsilateral STA was supplied from the contralateral STA. The procedure was
      accomplished without difficulty, and no further ischemic symptoms developed after
      surgery. Postoperative cerebral angiography demonstrated an increase in
      collateral flow to the anastomosed bonnet STA and perfusion to an entire
      territory of the upper trunk of the symptomatic middle cerebral artery via the
      anastomosis. CONCLUSION: This case suggests that arterial bypass surgery can be
      performed using a spontaneously formed bonnet STA as a donor in a patient with
      symptomatic CCA occlusion.

PMID- 20679913
TI  - A variation of the infraorbital nerve: its potential clinical consequence
      especially in the treatment of trigeminal neuralgia: case report.
AB  - OBJECTIVE: We report the case of a seemingly rare variation of a branch of the
      trigeminal nerve. This unusual finding is of practical importance to the
      neurosurgeon because ablation of this nerve(s) in such a case would require
      modification of technique. The existence of a bifurcated infraorbital nerve is
      also relevant for application of local anesthesia to portions of the face
      innervated by the maxillary nerve. CLINICAL PRESENTATION: During cadaveric
      dissection of the face of a male specimen, 2 branches of the infraorbital nerve
      were identified emanating onto the face. The 2 branches entered separate osseous
      canals within the orbit to emerge via 2 infraorbital foramina. INTERVENTION: The
      unusual variation of the trigeminal nerve branch in the reported case
      necessitates a change in the way in which the nerve is blocked clinically. A
      common practice involves blocking the infraorbital nerve as it emerges from the
      infraorbital foramen. The needle is aimed superiorly, posteriorly, and slightly
      laterally; however, to provide adequate anesthesia to both branches of the
      infraorbital nerve, as reported here, a needle can be inserted between the
      zygomatic arch and the notch of the mandible in the pterygopalatine fossa. After
      the needle contacts the lateral pterygoid plate, it is withdrawn slightly and
      angled both superiorly and anteriorly to pass into the pterygopalatine fossa.
      CONCLUSION: Although apparently uncommon, such derangement of the infraorbital
      nerve should be kept in mind by surgeons during surgical procedures in the region
      for treatment of various disorders including trigeminal neuralgia.

PMID- 20679914
TI  - Very late thrombosis of a pipeline embolization device construct: case report.
AB  - BACKGROUND: The Pipeline embolization device (PED) is a new endoluminal construct
      designed to exclude aneurysms from the parent cerebrovasculature. We report the
      very late (>1 year) thrombosis of a PED construct placed for the treatment of a
      left vertebral aneurysm. CLINICAL PRESENTATION: A patient with an occluded right
      vertebral artery and a large, fusiform intracranial left vertebral artery
      aneurysm was treated with PED and coil reconstruction. A durable, complete
      occlusion of the aneurysm was confirmed with control angiography at 1 year. The
      patient remained neurologically normal for 23 months until he experienced a
      transient visual disturbance followed weeks later by a minor brainstem stroke.
      INTERVENTION: Imaging evaluation showed thrombosis of the PED construct with
      complete occlusion of the left vertebral artery. After this stroke, he was
      initially treated with dual antiplatelet therapy and was then converted to
      warfarin. The patient remained neurologically stable for 5 months until he
      experienced progressive basilar thrombosis that ultimately resulted in a fatal
      stroke. CONCLUSION: The PED represents a promising new endovascular technology
      for the treatment of cerebral aneurysms; however, as an investigational device,
      long-term follow-up data are sparse at this point. The etiology of the very late
      thrombosis of the PED construct in this case remains unknown; however, this
      report underscores the need for a continued, careful systematic evaluation and
      close long-term follow-up of treated patients.

PMID- 20679915
TI  - Remora technique to approach the affected, difficult to approach sinus at
      transvenous embolization for dural arteriovenous fistulae: case report.
AB  - BACKGROUND AND IMPORTANCE: We describe a novel technique that uses a goose neck
      snare for microcatheterization at transvenous embolization (TVE) for dural
      arteriovenous fistulae (dAVF). We have named our method the "remora technique."
      CLINICAL PRESENTATION: A 48-year-old man reported with dizziness. Angiography
      disclosed a transverse-sigmoid sinus (T-SS) dAVF with proximal sigmoid sinus
      occlusion, an open distal transverse sinus, narrow multiple divided confluence
      sinus, and multiple retrograde leptomeningeal venous drainage. We attempted TVE
      via the confluence sinus from the contralateral open side; it was narrow, steep,
      and divided into cavities, rendering the procedure very difficult. Although we
      were able to pass a 0.035-inch guidewire to the affected transverse sinus, we
      could not advance via the same route with the microguidewire. One month later we
      attempted transfemoral TVE again using the remora technique. We caught the 0.035
      inch guidewire in the left internal jugular vein with a goose neck micro snare
      bearing a microcatheter. By advancing the 0.035-inch wire across the confluence
      sinus to the affected sinus, we were able to pass the microcatheter through the
      lesion using the snare like a remora. We then performed transvenous coil packing.
      CONCLUSION: In TVE for dAVF, passage of the microguidewire is often difficult.
      Even if the affected sinus can be reached with the stiff 0.035-inch guidewire, it
      may not be possible to follow with the microguidewire. We report on a patient
      with T-SS dAVF who underwent successful microcatheterization in which we used our
      remora technique with a goose neck snare.

PMID- 20679916
TI  - Arteriovenous micromalformation of the trigeminal root: intraoperative diagnosis
      with indocyanine green videoangiography: case report.
AB  - BACKGROUND AND IMPORTANCE: To report on a single case of arteriovenous
      micromalformation (micro-AVM) of the trigeminal root that was diagnosed during
      microvascular decompression for trigeminal neuralgia with the use of indocyanine
      green (ICG) videoangiography. CLINICAL PRESENTATION: A 52-year-old woman with
      drug-resistant trigeminal neuralgia underwent a key hole suboccipital
      cerebellopontine angle exploration after the usual magnetic resonance imaging
      (MRI) screening had raised the suspicion of a vascular compression. In surgery,
      the petrosal vein was found to be bigger than usual and arterialized; the
      trigeminal root was embedded in a tangle of abnormal arterialized vessels.
      Intraoperative ICG videoangiography showed that the direction of flow in the
      arterialized petrosal vein was anterograde, thus allowing for the differential
      diagnosis between micro-AVM and tentorial dural fistula. It was possible to
      achieve only a partial nerve decompression because of the intimate relationship
      between the trigeminal root and the pathological vessels. Postoperative
      angiography and MRI with contrast administration confirmed the intraoperative
      diagnosis of micro-AVM. The patient was discharged neurologically intact on
      postoperative day 4. One month after surgery, she remains pain-free despite a 50%
      reduction in antiepileptic drugs. CONCLUSION: Surgeons performing microvascular
      decompression should be aware that a diagnosis of vascular compression based on
      MRI without contrast administration could not exclude the presence of a pontine
      micro-AVM. ICG videoangiography provides an elegant means of showing the flow
      dynamics of these pathological vessels. An MRI protocol that is suitable to avoid
      this kind of intraoperative drawback should be defined and systematically used in
      the preoperative evaluation of all such surgical candidates.

PMID- 20679917
TI  - A novel method for administering intrathecal chemotherapy in patients with
      leptomeningeal metastases and shunted hydrocephalus: case report.
AB  - BACKGROUND AND IMPORTANCE: Leptomeningeal metastatic disease occurs in a minority
      of patients with systemic neoplastic disease. Before the initiation of
      intrathecal chemotherapy, hydrocephalus must be addressed with a cerebrospinal
      fluid (CSF)-diverting shunt. CSF diversion can theoretically prematurely divert
      chemotherapeutic drugs that are administered intrathecally, thereby potentially
      reducing the efficacy of such treatments. CLINICAL PRESENTATION: We report on a
      patient with leptomeningeal disease and hydrocephalus secondary to metastatic
      bladder carcinoma requiring insertion of a programmable ventriculoperitoneal
      shunt and intrathecal chemotherapy. A novel method was utilized to administer
      intrathecal chemotherapy, in which the valve pressure setting was transiently
      increased during a 4-hour treatment session for intrathecal chemotherapy. No
      clinical complications occurred. Nuclear imaging was obtained sequentially after
      the injection of indium tracer into the ventricular system with the programmable
      valve at its baseline setting as well as at a maximal pressure setting. In the
      maximal valve setting condition, reduced outflow of nuclear tracer was observed
      at 1.5 and 4 h after injection, and normalized by 24 hours after injection.
      CONCLUSION: Programmable shunt valves can be utilized in a safe, controlled
      fashion to treat hydrocephalus associated with leptomeningeal disease, as well as
      regulate the outflow of CSF and minimize diversion of intrathecal
      chemotherapeutic agents.

PMID- 20679918
TI  - Demonstration of intraluminal thrombus in the carotid artery by optical coherence
      tomography: technical case report.
AB  - OBJECTIVE: Intraluminal thrombus in the carotid artery is often misdiagnosed
      because clinical imaging, such as angiography and duplex ultrasonography, fails
      to accurately identify it. Recently, it was reported that optical coherence
      tomography (OCT), a new imaging modality, can visualize intravascular thrombus in
      the coronary artery. CLINICAL PRESENTATION: An 83-year old male was admitted due
      to newly developed motor weakness of the left hand. Diffusion weighted magnetic
      resonance imaging showed multiple high intensity spots in the territory of the
      right middle cerebral artery, and magnetic resonance angiography revealed
      significant stenosis at the origin of the right internal carotid artery. Because
      of an apparent change in plaque shape on the angiogram just before carotid artery
      stenting, further examinations such as intravascular ultrasonography (IVUS) and
      OCT were performed. EXAMINATION: After IVUS examination, both the common carotid
      and external carotid arteries were occluded by an occlusion balloon system
      prepared for carotid artery stenting. Then the stenotic site was imaged by OCT
      from the distal section at 1 mm/sec using a built-in pull-back system with
      continuous injection of saline through the guiding catheter to remove blood from
      the field of view. Since intraluminal thrombus was clearly demonstrated by an
      OCT, carotid endarterectomy was performed instead of stenting, and thrombus was
      confirmed by surgical specimen. CONCLUSION: OCT may provide useful information
      for diagnosis of an intraluminal thrombus in the carotid artery, which is
      important for the appropriate selection of therapeutic strategy.

PMID- 20679919
TI  - In vivo retrieval of a trapped Merci embolectomy device: technical case report.
AB  - BACKGROUND AND IMPORTANCE: This technical note describes a complication related
      to the use of the Merci embolectomy device not previously reported. The device
      can induce critical flow limitation within an accessed vessel because of a
      combination of vasospasm and anatomic conformational changes. Furthermore, this
      can limit the safe removal of the device from intracranial vasculature. We
      present a novel rescue technique that can be used to safely retrieve the
      entrapped Merci device without inciting localized vessel injury. CLINICAL
      PRESENTATION: A 51-year-old male with embolic occlusion of the distal basilar
      artery and dissection-related occlusion of the left cervical vertebral underwent
      mechanical thrombolysis. Flow-limiting vasospasm and/or anatomic conformational
      changes/ telescoping of the intracranial right vertebral artery segment was
      induced during deployment with subsequent entrapment of the device. Reclamation
      of the entrapped device was performed by initially removing the Merci
      microcatheter. The entrapped and fixated device was then resheathed into a 4F
      slip catheter within the intracranial vertebral artery. The Merci device and the
      slip catheter were then removed. Right vertebral and proximal basilar artery flow
      was reestablished after removal of the Merci device. Successful clot extraction
      was thereafter performed using a microsnare. CONCLUSION: In vitro assessment of
      the device has demonstrated its propensity to induce vasospasm. In vivo
      entrapment of the device has not been previously reported. Successful retrieval
      can be achieved if the Merci device becomes entrapped and fixated. This may be an
      important consideration as increased utilization of the device occurs.

PMID- 20679920
TI  - Intraoperative use of indocyanine green fluorescence videography for resection of
      a spinal cord hemangioblastoma.
AB  - BACKGROUND AND IMPORTANCE: Indocyanine green (ICG) fluorescence videography has
      been recently applied to the neurosurgical field, mostly in the management of
      cerebral aneurysms, but has had limited description in the subspecialty of spine
      or oncological neurosurgery. We describe a novel application of this previously
      defined surgical tool to assist in the resection of a residual spinal cord
      hemangioblastoma. CLINICAL PRESENTATION: Our patient is a 49-year-old woman with
      a residual symptomatic cervical hemangioblastoma that was previously embolized
      and resected at another institution. After initial symptomatic improvement, she
      returned with progressive symptoms, increasing radiographic spinal cord edema,
      and a residual lesion at the level of C1. We resected the remaining tumor with
      the adjuvant use of ICG fluorescence videography. Intraoperative injection of ICG
      clearly identified a component of the tumor underlying adhesive, opaque arachnoid
      that was not visualized by direct microscopy. Immediate postresection ICG
      videography suggested a complete resection was achieved which was later
      corroborated by postoperative magnetic resonance imaging. CONCLUSION: The
      adjuvant use of ICG videography is a useful surgical tool that permits greater
      visualization of the complete extent of the lesion, particularly in managing
      recurrent or residual lesions obscured by adhesions.

PMID- 20679921
TI  - Meckel's cave tumors: relation to the meninges and minimally invasive approaches
      for surgery: anatomic and clinical studies.
AB  - BACKGROUND: Literature on tumors originating from Meckel's cave (MC) and their
      surgical treatment are scarce. OBJECTIVE: We present 37 cases of tumors
      originating from MC, the largest single-institution series reported thus far, and
      discuss the ideal surgical methods for each tumor type in relation to the normal
      and pathological anatomy of MC. METHODS: We studied 37 cases of surgery for
      tumors in MC (26 schwannomas, 7 meningiomas, 2 epidermoids, 1 hemangiopericytoma,
      and 1 dermoid) performed at our institution between 1986 and 2008. We excluded
      cases of large tumors of unknown origin, especially meningiomas. Surgery for
      tumors in MC was performed via 2 approaches: anterolateral interdural access
      (Dolenc's) approach and posterior access via the anterior petrosal approach
      (APA). RESULTS: The Dolenc approach was useful for parasellar tumors, especially
      schwannomas, because it resulted in minimal damage to the temporal lobe and
      adjacent cranial nerves. The APA was useful for dumbbell-shaped tumors extending
      into the posterior fossa. Tumors of nonmeningeal origin (schwannomas,
      epidermoids, and dermoids) were safely resected, with no postoperative
      complications except facial hypesthesia. However, incidence of postsurgical
      paresthesia and abducens palsy were higher in meningioma and hemangiopericytoma,
      because of invasion into the Gasserian ganglion, the cavernous sinus (CS), or
      Dorello's canal. CONCLUSION: An understanding of meningeal structure around MC
      enhances the radicality of tumor resection and helps minimize damage to adjacent
      structures. However, meningiomas and hemangiopericytomas occurring in MC, which
      can infiltrate into the CS, should be treated by both surgery and radiosurgery to
      minimize postoperative complications.

PMID- 20679922
TI  - Experimental simplification of the excimer laser-assisted nonocclusive
      anastomosis (ELANA) technique.
AB  - BACKGROUND: The excimer laser-assisted nonocclusive anastomosis (ELANA) technique
      facilitates the construction of an end-to-side anastomosis between a donor vessel
      and a recipient artery without the need to temporarily occlude the recipient
      artery. OBJECTIVE: To test whether the surgically difficult ELANA technique can
      be simplified. METHODS: In 42 rabbits, with the aorta as the recipient artery and
      human saphenous veins as donor grafts, we made 30 conventional ELANAs with 8
      microsutures, 90 ELANAs with 4 microsutures (ELANA-4s), 40 ELANAs with 2
      microsutures (ELANA-2s), and 90 sutureless ELANAs (SELANAs). SELANA involved a
      new ring design with 2 pins. ELANA-4, ELANA-2, and SELANA were each combined with
      3 different sealants (Bioglue, Tachoseal, and Tisseel) and compared regarding
      application time, complications, and burst pressure. RESULTS: The conventional
      ELANA was constructed in a mean of 14.8 +/- 2.6 minutes. All experimental
      anastomoses were constructed significantly faster; the ELANA-4 in a mean of 10.9
      +/- 1.3 minutes, the ELANA-2 in a mean of 5.4 +/- 1.7 minutes, and the SELANA in
      a mean of 2.5 +/- 1.8 minutes. All ELANA and ELANA-4 anastomoses were
      sufficiently strong with a burst pressure > 200 mm Hg, except for 1
      insufficiently sealed ELANA-4 anastomosis. ELANA-2 was sufficiently strong only
      with Bioglue, showing a burst pressure > 280 mm Hg. SELANA was sufficiently
      strong with Bioglue or TachoSil, showing a burst pressure > 260 mm Hg.
      CONCLUSION: The ELANA technique can be simplified by reducing or even abandoning
      microsutures. Of the experimental anastomoses tested, we consider the SELANA
      technique combined with TachoSil of most potential benefit. Long-term survival
      studies will be performed in animals before we consider using any of these new
      techniques in patients.

PMID- 20679923
TI  - Brain retraction and thickness of cerebral neocortex: an automated technique for
      detecting retraction-induced anatomic changes using magnetic resonance imaging.
AB  - BACKGROUND: Treating deep-seated cerebral lesions often requires retracting the
      brain. Retraction, however, causes clinically significant postoperative
      neurological deficits in 3% to 9% of intracranial cases. OBJECTIVE: This pilot
      study used automated analysis of postoperative magnetic resonance images (MRIs)
      to determine whether brain retraction caused local anatomic changes to the
      cerebral neocortex and whether such changes represented sensitive markers for
      detecting brain retraction injury. METHODS: Pre- and postoperative maps of whole
      brain cortical thickness were generated from 3-dimensional MRIs of 6 patients who
      underwent selective amygdalohippocampectomy for temporal lobe epilepsy (5 left
      hemispheres, 1 right hemisphere). Mean cortical thickness was determined in the
      inferior temporal gyrus (ITG test), where a retractor was placed during surgery,
      and in 2 control gyri-the posterior portion of the inferior temporal gyrus (ITG
      control) and motor cortex control. Regions of cortical thinning were also
      compared with signs of retraction injury on early postoperative MRIs. RESULTS:
      Postoperative maps of cortical thickness showed thinning in the inferior temporal
      gyrus where the retractor was placed in 5 patients. Postoperatively, mean
      cortical thickness declined from 4.1 +/- 0.4 mm to 2.9 +/- 0.9 mm in ITG test (P
      = .03) and was unchanged in the control regions. Anatomically, the region of
      neocortical thinning correlated with postoperative edema on MRIs obtained within
      48 hours of surgery. CONCLUSION: Postoperative MRIs can be successfully
      interrogated for information on cortical thickness. Brain retraction is
      associated with chronic local thinning of the neocortex. This automated technique
      may be sensitive enough to detect regions at risk for functional impairment
      during craniotomy that cannot be easily detected on postoperative structural
      imaging.

PMID- 20679924
TI  - Microvascular anatomy of the medial temporal region: part 1: its application to
      arteriovenous malformation surgery.
AB  - BACKGROUND: The medial temporal region (also called the temporomesial or
      mediobasal temporal region) is the site of the most complex cortical anatomy.
      OBJECTIVE: To investigate the anatomic variability of the arterial supply and
      venous drainage of each segment of the medial temporal region (MTR), and to
      discuss and illustrate the implications of the findings for surgery of
      arteriovenous malformations (AVM) of the MTR. METHODS: Forty-seven cerebral
      hemispheres and 10 silicon-injected cadaveric heads were examined using x3 to x40
      magnification. Illustrative surgical cases of MTR AVMs were selected. RESULTS:
      The anterior choroidal artery (AChA) gave rise to an anterior uncal artery in 83%
      of hemispheres and a posterior uncal or unco-hippocampal artery in 98%. The
      plexal segment of the AChA gave off neural branches in 38%. The MCA was the site
      of origin of anterior uncal, unco-parahippocampal, or anterior parahippocampal
      arteries in 94% of hemispheres. An anterior uncal artery arose from the internal
      carotid artery (ICA) in 45% of hemispheres. The posterior cerebral artery (PCA)
      irrigated the entorhinal area through its anterior parahippocampal or hippocampo
      parahippocampal branches in every case. A PCA bifurcation was identified in 89%
      of hemispheres, typically at the middle segment of the MTR. The most common
      pattern of bifurcation was by division into posteroinferior temporal and parieto
      occipital arterial trunks. The anterior segment of the basal vein had a
      predominant anterior drainage in 35% of hemispheres, and the middle segment had a
      predominant inferior drainage in 16%. CONCLUSION: An understanding of the
      vascular variability of the MTR is essential for accurate microsurgical resection
      of MTR AVMs.

PMID- 20679925
TI  - Anterior fixation of the axis.
AB  - BACKGROUND: Although anterior fixation of the axis is not commonly performed,
      plate fixation of C2 is an important technique for treating select upper cervical
      traumatic injuries and is also useful in the surgical management of spondylosis.
      OBJECTIVE: To report the technique and outcomes of C2 anterior plate fixation for
      a series of patients in which the majority presented with symptomatic
      degenerative spondylosis. METHODS: Forty-six consecutive patients underwent
      single or multilevel fusions over a 7-year period; 30 of these had advanced
      degenerative disease manifested by myelopathy or deformity. Exposure was achieved
      with rostral extension of the standard anterior cervical exposure via careful
      soft tissue dissection, mobilization of the superior thyroid artery, and the use
      of a table-mounted retractor. It was not necessary to remove the submandibular
      gland, section the digastric muscle, or make additional skin incisions. RESULTS:
      Screws were placed an average of 4.6 mm (+/- 2.3 mm) from the inferior C2
      endplate with a mean sagittal trajectory of 15.7 degrees (+/- 7.6 degrees). Short
      and long-term procedure-related mortality was 4.4%, and perioperative morbidity
      was 8.9%. Patients remained intubated an average of 2.5 days following surgery.
      Dysphagia was initially reported by 15.2% of patients but resolved by the 8th
      postoperative week in all patients. Arthrodesis was achieved in all patients
      available for long-term follow-up. Multilevel fusions were not associated with
      longer hospitalization or morbidity. CONCLUSION: Anterior plate fixation of the
      axis for degenerative disease can be accomplished with acceptable morbidity
      employing an extension of the standard anterolateral route.

PMID- 20679926
TI  - Utility and the limit of motor evoked potential monitoring for preventing
      complications in surgery for cerebral arteriovenous malformation.
AB  - OBJECTIVE: To evaluate the usefulness of motor evoked potential (MEP) monitoring
      and mapping in arteriovenous malformation surgery. METHODS: Intraoperative MEP
      monitoring was performed in 21 patients whose AVMs were located near the motor
      area or fed by arteries related to the corticospinal tract to detect blood flow
      insufficiency and/or direct injury to the corticospinal tract and/or to map the
      motor area. RESULTS: In 4 of 16 patients monitored for blood flow insufficiency,
      the MEP changed intraoperatively. In 2 patients, the changes were attributable to
      temporary occlusion of the feeding artery (anterior choroidal or lenticulostriate
      artery): 1 patient had a venous infarction around the internal capsule caused by
      thrombosis of the draining vein and the other bled intraoperatively from the
      nidus. In 17 patients, the MEP was monitored to rule out direct injury. In 1
      patient, the MEP changed on coagulation of fragile vessels around the nidus in
      the precentral gyrus; it recovered after coagulation was discontinued. In 1 of 5
      patients with MEP changes, the MEP did not recover; permanent hemiparesis
      developed in this patient because of venous infarction. In 1 of 11 patients
      subjected to MEP mapping of the motor area, we found translocation to the
      postcentral sulcus. CONCLUSION: In arteriovenous malformation surgery, MEP
      monitoring facilitates the detection of blood flow insufficiency and/or direct
      injury of the corticospinal tract and mapping of the motor area. It contributes
      to reducing the incidence of postoperative motor paresis.

PMID- 20679927
TI  - Minimizing brain shift in stereotactic functional neurosurgery.
AB  - BACKGROUND: Stereotactic functional neurosurgical interventions depend on precise
      anatomic targeting before lesioning or deep brain stimulation (DBS) electrode
      placement. OBJECTIVE: To examine the degree of subcortical brain shift observed
      when adopting an image-guided approach to stereotactic functional neurosurgery.
      METHODS: Coordinates for the anterior and posterior commissural points (AC and
      PC) were recorded on thin-slice stereotactic magnetic resonance imaging (MRI)
      scans performed before and immediately after DBS electrode implantation in 136
      procedures. The changes in length of AC-PC and in stereotactic coordinates for AC
      and PC were calculated for each intervention. In patients with Parkinson disease
      undergoing bilateral subthalamic nucleus (STN) DBS with at least 6 months of
      follow-up, pre- and postoperative scores of the motor part of the Unified
      Parkinson's Disease Rating Scale (UPDRS-III) were reviewed. RESULTS: Mean (SD)
      change in AC-PC length (DeltaAC-PC) was 0.6 (0.4) mm. There was no statistically
      significant difference in DeltaAC-PC between groups when examining anatomic
      target subgroups (P =.95), age subgroups (P = .63), sex (P = .59), and unilateral
      versus bilateral implantation (P =.15). The mean (SD) vector changes for the
      commissural points were: -0.1 (0.3) mm in X, -0.4 (0.6) mm in Y, and -0.1 (0.7)
      mm in Z for the AC; and -0.1 (0.3) mm in X, -0.2 (0.7) mm in Y, and 0.0 (0.7) mm
      in Z for the PC. There was a negligible correlation between the magnitude of
      brain shift and percentage improvement in UPDRS-III off-medication in patients
      undergoing STN DBS for PD (R <0.01). CONCLUSION: Brain shift has long been
      considered an issue in stereotactic targeting during DBS procedures. However,
      with the image-guided approach and surgical technique used in this study,
      subcortical brain shift was extremely limited and did not appear to adversely
      affect clinical outcome.

PMID- 20679928
TI  - Spinal cord stimulation for central poststroke pain.
AB  - BACKGROUND: Although spinal cord stimulation (SCS) has been shown to be effective
      for treating neuropathic pain of peripheral origin, its effectiveness for central
      poststroke pain (CPSP) is not well established. OBJECTIVE: We report our
      experience with SCS in 30 consecutive patients with intractable CPSP. METHODS:
      All patients underwent a percutaneous SCS trial. When patients decided to
      proceed, they received a permanent SCS system. Pain intensity was evaluated by a
      visual analogue scale (VAS). The Patient Global Impression of Change (PGIC) scale
      was also assessed at the latest follow-up visit as an indicator of overall
      improvement. RESULTS: During trial stimulation, pain relief was good (> or =50%
      VAS score reduction) in 9 patients (30%), fair (30%-49% reduction) in 6 patients
      (20%), and poor (<30% reduction) in 15 patients (50%). Ten patients elected to
      receive a permanent SCS system. Nine of these 10 patients were followed long-term
      (mean, 28 months; range, 6-62 months). Seven patients reported significant pain
      relief on the VAS (5 = good and 2 = fair). On the PGIC scale, 6 of these 7
      patients reported a rating of 2 (much improved) and 1 reported a rating of 3
      (minimally improved). Of the remaining 2 patients, 1 reported a rating of 4 (no
      change) and 1 reported a rating of 5 (minimally worse). The median VAS score in
      the 9 patients decreased significantly from 8.6 (range, 6.0-10.0) to 4.5 (range,
      3.0-8.0; P = .008). There were no significant reported complications. CONCLUSION:
      SCS may provide improved pain control in a group of patients with intractable
      CPSP and may have therapeutic potential for intractable CPSP.

PMID- 20679929
TI  - Stereotactically guided endoscopic port surgery for intraventricular tumor and
      colloid cyst resection.
AB  - BACKGROUND: Intraventricular lesions are challenging entities that may be
      difficult to resect completely and safely, especially larger lesions with high
      vascularity or firm consistency. OBJECTIVE: To assess the results of
      stereotactically guided endoscopic port (SEP) surgery for resection of colloid
      cysts and intraventricular tumors. METHODS: The authors developed a minimally
      invasive microsurgical technique for intraventricular surgery using parallel
      endoscopy to visualize the lesion. Surgical resection was performed via an 11.5
      mm transparent conduit (Neuroendoport) deployed under stereotactic guidance.
      Forty-seven consecutive cases were performed, and all had a minimum 1-year follow
      up to assess the efficacy of the technique. RESULTS: For colloid cysts, gross
      total resection was achieved in 31 (96.9%) of the 32 cases. The transient
      neurologic morbidity rate was 9.4%; no permanent neurologic morbidity occurred.
      For intraventricular tumors, gross or near total resection was achieved in 80% of
      cases. The transient neurological morbidity rate was 6.7%, and no permanent
      neurological morbidity occurred. CONCLUSION: SEP surgery for colloid cysts and
      intraventricular tumors proved to be a safe and effective alternative to
      conventional microsurgical resection. This technique was not limited by the
      vascularity, friability, or size of any of the lesions.

PMID- 20679930
TI  - Percutaneous balloon angioplasty for acute occlusion of intracranial arteries.
AB  - BACKGROUND: The benefits of intravenous thrombolysis for acute ischemic stroke
      are still limited. OBJECTIVE: To evaluate the safety and efficacy of double-lumen
      balloon catheter-based reperfusion therapy with or without intra-arterial
      thrombolysis for acute occlusion of intracranial arteries. METHODS: Fifty-nine
      patients with acute occlusion of intracranial arteries were enrolled. A Gateway
      balloon catheter was used to disrupt clots or dilate atheromatous plaques in
      every patient. The technical details, technique-related complications,
      recanalization rates, and clinical outcomes were analyzed. RESULTS: The occlusion
      sites were internal carotid arteries in 17 patients, M1 segments in 32 patients,
      the M2 segment in 1 patient, a vertebral artery in 1 patient, and basilar
      arteries in 8 patients. Twenty-four patients (41%) were treated with thrombolysis
      first, and 20 patients (34%) were treated with percutaneous transluminal
      angioplasty (PTA) followed by thrombolysis. PTA alone was performed in 15
      patients (25%). The mean dose of urokinase was 205 x 10 U. The extent of
      recanalization was complete (Thrombolysis in Myocardial Infarction [TIMI] score
      of 3) in 17 patients (29%), and partial (TIMI 1/2) in 28 patients (47%).
      Functional independence at discharge was preserved in 76%, 25%, and 7% of
      patients with TIMI 3, TIMI 1/2, and TIMI 0, respectively. A combination of PTA
      and thrombolysis resulted in a significantly higher recanalization rate than PTA
      only. Seven patients (12%) experienced hemorrhagic events after treatment. Severe
      parenchymal hemorrhage with neurologic deterioration was observed in 2 patients
      (4%), and vessel rupture was encountered in 1 atherosclerotic case. CONCLUSIONS:
      Mechanical angioplasty using a Gateway catheter combined with a low-dose
      thrombolytic agent is a safe and effective treatment for acute intracranial
      embolic and atherosclerotic occlusion with a low risk of hemorrhagic
      complications.

PMID- 20679931
TI  - A comparative analysis of the results of vertebroplasty and kyphoplasty in
      osteoporotic vertebral compression fractures.
AB  - BACKGROUND: The most common complication of osteoporosis is vertebral fractures,
      which occur more frequently than all other fractures (hip, wrist, and ankle).
      OBJECTIVE: To prospectively analyze vertebroplasty compared with kyphoplasty for
      the treatment of osteoporotic vertebral compression fractures using improvement
      in pain, functional capacity, and quality of life as outcome measures. METHODS:
      The study population included 28 patients in the vertebroplasty group and 24
      patients in the kyphoplasty group. The mean follow-up period was 42.2 weeks and
      42.3 weeks in the vertebroplasty and kyphoplasty groups, respectively. Outcomes
      were measured pre- and postoperatively using the visual analogue scale, the
      Oswestry Disability Index, the EuroQol-5D questionnaire, and the Short-Form 36
      Health Survey. RESULTS: In the vertebroplasty group, visual analogue scale scores
      improved from a mean of 8.0 cm to 5.5 cm at last follow-up (P = .001).
      Preoperatively, the Oswestry Disability Index was 57.6, which improved to 38.4 (P
      = .006). The EuroQol-5D score preoperatively was 0.157 and improved to 0.504 (P =
      .001). The Short-Form 36 Health Survey showed greatest improvement in the areas
      of physical health, role physical, body pain, and vitality. In the kyphoplasty
      group, visual analogue scale scores improved from a mean of 7.5 cm preoperatively
      to 2.5 cm postoperatively (P = .000001). The mean Oswestry Disability Index
      preoperatively was 50.7 and improved to 28.8 (P = .002). The EuroQol-5D score
      improved from a mean of 0.234 preoperatively to 0.749 (P = .00004). The Short
      Form 36 Health Survey showed greatest improvement in the areas of physical
      health, physical functioning, role physical, body pain, and social functioning.
      CONCLUSION: Both vertebroplasty and kyphoplasty are effective at improving pain,
      functional disability, and quality of life; however, kyphoplasty provides better
      results, which are maintained over long-term follow-up.

PMID- 20679932
TI  - Acute intraprocedural thrombus formation during wingspan intracranial stent
      placement for intracranial atherosclerotic disease.
AB  - BACKGROUND: Treatment of intracranial atherosclerotic disease with the Wingspan
      Gateway intracranial stent and balloon angioplasty system has been reported in
      several multicenter registries. To date, the incidence of acute intraprocedural
      thrombus formation during Wingspan stent placement has not been reported.
      OBJECTIVE: We reviewed the incidence of acute thrombus formation, treatment, and
      outcome for patients who underwent Wingspan stent placement by the senior author
      (B.L.H.) between June 2006 and April 2009. METHODS: We routinely perform
      angiograms every 10 minutes for at least 30 minutes after placement of a Wingspan
      stent to check for acute thrombus formation. Acute thrombus was graded: (1)
      visible thrombus but not flow limiting, (2) visible and flow-limiting thrombosis,
      and (3) complete stent occlusion. Recanalization was graded according to
      Thrombosis In Myocardial Infarction score. RESULTS: Forty-one patients underwent
      Wingspan stent placement for intracranial stenosis. Acute intraprocedural
      thrombus formation developed in 6 (14.6%) within 20 minutes after stent
      placement: 3 grade 1, 1 grade 2, and 2 grade 3. All 6 were successfully
      recanalized with Thrombosis In Myocardial Infarction score 3 after intravenous
      abciximab with or without intra-arterial tissue plasminogen activator and/or
      balloon angioplasty. There was no morbidity, and all 6 patients were discharged
      home at their neurological baseline. CONCLUSION: We recommend serial angiography
      every 10 minutes for at least 30 minutes after placement of Wingspan stents. Once
      detected, acute thrombosis can be successfully treated with intravenous abciximab
      with or without intra-arterial tissue plasminogen activator and/or balloon
      angioplasty.

PMID- 20679933
TI  - The value of endoscopy in the total resection of pineocytomas.
AB  - BACKGROUND: Pineocytomas are rare pineal region tumors. The mainstay of treatment
      for pineocytomas is total surgical resection. OBJECTIVE: To address the
      worthiness of endoscopy to achieve total macroscopic resection and whether or not
      this portends better progression-free and overall survival. METHODS: A series of
      15 patients (11 females, 4 males; mean age, 48 years) with histological diagnosis
      of pineocytoma were retrospectively reviewed. All patients underwent an attempt
      at total resection via an interhemispheric/transtentorial/retrosplenial approach.
      The endoscope was used at various times throughout the case and consistently at
      the end to evaluate any possible residual tumor. No patient in this series was
      given radiotherapy after surgery. RESULTS: There was no surgical mortality and
      all patients are currently alive without recurrence (mean follow-up, 4.28 years).
      A macroscopic and radiological complete removal was achieved in all cases. There
      was only one patient with permanent neurological deficit (disconjugate eye
      movements). Two patients (13%) had transient poor sleep pattern, 5 patients (33%)
      had transient disconjugate eye movements, and 2 patients (13%) had transient
      short-term memory disturbance. In 6 cases (40%), the endoscope was able to detect
      residual tumor located either behind the Vein of Galen or attached to the
      undersurface of the corpus callosum. Residual tumor was then resected using a 30
      degrees endoscope and dedicated angled endoscopic instruments. CONCLUSIONS: This
      series demonstrates the advantage of endoscopic-assisted surgery in the total
      removal of pineocytomas. With total removal of these histologically benign tumors
      patients may enjoy extended progression-free survival without adjuvant
      radiotherapy.

PMID- 20679934
TI  - Endoscopic endonasal minimal access approach to the clivus: case series and
      technical nuances.
AB  - BACKGROUND: The endoscopic endonasal transclival approach is a novel minimal
      access method of managing clival pathology. Limited cases have been published.
      OBJECTIVE: To summarize our clinical experience with this approach and discuss
      technical nuances. METHODS: We retrospectively reviewed a prospective database of
      250 endoscopic, endonasal skull base surgeries. Patients in whom a transclival
      approach was performed were identified. Extent of resection, complications, and
      clinical outcome were analyzed. RESULTS: Seventeen patients underwent 21
      procedures. Pathology included chordoma, meningioma, hemangiopericytoma,
      enterogenous cyst, epidermoid, and metastasis. Lumbar drain was placed
      intraoperatively in 9 cases and maintained for approximately 2 days
      postoperatively. Mean operative time was 252.8 minutes. Intraoperative
      cerebrospinal fluid (CSF) leak occurred in 10 cases. Greater than 95% resection
      was achieved in 11 of 12 cases (92%) in which it was the surgical goal. The risk
      of postoperative CSF leak was 4.8% for all procedures, 9.1% for procedures with
      large skull base defect, and 0% if a gasket-seal closure was achieved. A
      nasoseptal flap was used in 2 patients. There was one perioperative infarct, one
      case of deep vein thrombosis, and one postoperative pulmonary embolus. Mean
      follow-up was 8.5 months. All but one patient with preoperative cranial nerve
      deficits improved at last follow-up. All patients were free of disease
      progression at last follow-up. CONCLUSIONS: The endonasal endoscopic transclival
      approach provides a minimal-access approach to the ventral midline posterior
      fossa skull base. The risk of CSF leak is low if appropriate closure techniques
      are applied.

PMID- 20679935
TI  - Successful superficial temporal artery-anterior cerebral artery direct bypass
      using a long graft for moyamoya disease: technical note.
AB  - BACKGROUND: Although some patients with moyamoya disease need revascularization
      in the anterior cerebral artery (ACA) territory, there are few reports on direct
      bypass in the ACA territory because of the difficult surgical technique.
      OBJECTIVE: To report our technical strategy for superficial temporal artery (STA)
      ACA bypass. METHODS: We performed simultaneous STA-ACA and STA-middle cerebral
      artery direct bypasses in 7 patients with moyamoya disease using the following
      strategies: creating 2 separate craniotomies for the 2 bypasses, dissecting a
      long STA graft and securing a recipient ACA around the bregma for the STA-ACA
      bypass, and using loose stitches at the anastomoses. One branch of the STA was
      dissected for a length of approximately 10 cm. The graft coursed on the brain
      surface under the bone bridge and was directly anastomosed to the cortical branch
      of the ACA. At the anastomoses, the stitches were widely spaced and loose to
      facilitate expansion of the orifice. RESULTS: This method prevented kinking of
      the graft. Postoperative angiograms revealed good patency of the STA-ACA bypass
      in all patients. After the bypasses, 5 patients no longer had transient ischemic
      attacks or stroke, 1 patient was almost completely free of transient ischemic
      attacks, and 1 patient had only residual contralateral symptoms. In all 7
      patients, patency of the bypass was satisfactory during follow-up periods ranging
      from 9 to 23 months (mean 16.4 months). CONCLUSION: This method of STA-ACA bypass
      provides successful and reliable direct revascularization of the ACA territory in
      patients with moyamoya disease. Further investigation of the possible merit of
      this surgery in improving cognitive function is warranted.

PMID- 20679936
TI  - Endovascular treatment of a large aneurysm arising from a basilar trunk
      fenestration using the waffle-cone technique.
AB  - OBJECTIVE: Endovascular treatment of large intracranial aneurysms arising from a
      fenestrated parent vessel may prove particularly difficult. We present a case of
      a large, broad-based aneurysm arising from a proximal basilar artery (BA)
      fenestration treated with the waffle-cone technique. Technical nuances and
      indications for this treatment option are reviewed. CLINICAL PRESENTATION: A 38
      year-old man presented with headache, blurred vision, and dizziness. Angiography
      demonstrated an 11 x 14-mm BA aneurysm associated with the proximal portion of a
      BA fenestration. TECHNIQUE: A 28 x 4.5-mm Enterprise stent was placed from the
      right vertebral artery directly into the aneurysm. The stent tines were allowed
      to flare out in the aneurysm neck creating the "waffle cone." The aneurysm was
      then coiled with a series of Presidio coils. CONCLUSION: Use of the waffle-cone
      technique for stent placement resulted in nearly complete embolization of the
      aneurysm, retention of the entire coil mass in the dome, and preservation of flow
      through both vertebral arteries and both limbs of the fenestration.

PMID- 20679937
TI  - Ultrasound-guided, percutaneous peripheral nerve stimulation: technical note.
AB  - BACKGROUND: Peripheral nerve stimulation is a form of neuromodulation that
      applies electric current to peripheral nerves to induce stimulation paresthesias
      within the painful areas. OBJECTIVE: To report a method of ultrasound-guided,
      percutaneous peripheral nerve stimulation. This technique utilizes real-time
      imaging to avoid injury to adjacent vascular structures during minimally invasive
      placement of peripheral nerve stimulator electrodes. MATERIAL AND METHODS: We
      describe a patient that presented with chronic, bilateral foot pain following
      multiple foot surgeries, for whom a comprehensive, pain management treatment
      strategy had failed. We utilized ultrasound-guided, percutaneous tibial nerve
      stimulation at a thigh level to provide durable pain relief on the right side,
      and open peripheral nerve stimulation on the left. RESULTS: The patient
      experienced appropriate stimulation paresthesias and excellent pain relief on the
      plantar aspect of the right foot with the percutaneous electrode. On the left
      side, we were unable to direct the stimulation paresthesias to the sole of the
      foot, despite multiple electrode repositionings. A subsequent, open placement of
      a left tibial nerve stimulator was performed. This revealed that the correct
      electrode position against the tibial nerve was immediately adjacent to the
      popliteal artery, and was thus not appropriate for percutaneous placement.
      CONCLUSION: We describe a method of ultrasound-guided peripheral nerve
      stimulation that avoids the invasiveness of electrode placement via an open
      procedure while providing excellent pain relief. We further describe limitations
      of the percutaneous approach when navigating close to large blood vessels, a
      situation more appropriately managed with open peripheral nerve stimulator
      placement. Ultrasound-guided placement may be considered for patients receiving
      peripheral nerve stimulators placed within the deep tissues, and not easily
      placed in a blind fashion.

PMID- 20679938
TI  - A new tool for frameless stereotactic placement of ventricular catheters.
AB  - BACKGROUND: The accurate position of the ventricular catheter inside the frontal
      horn of the lateral ventricle is essential to prevent proximal failure in shunt
      surgery. For optimal placement, endoscopic- and image-guided techniques are
      available. OBJECTIVE: We introduce a newly constructed tool for quick and safe
      placement of ventricular catheters. It is mounted on a fixation device and
      therefore allows the surgeon's optimal concentration on the catheter insertion
      and feeling for the penetrated tissue. To check the feasibility of the new
      device, we performed a study with 4 patients. METHODS: Two patients with
      communicative and 2 patients with noncommunicative hydrocephalus underwent
      ventricular catheter placement using the new shunt placement tool. Three patients
      had a complex anatomy of the ventricular system. RESULTS: In all 4 procedures,
      correct placement of the ventricular catheters was achieved. The additional time
      needed for preparations did not exceed 15 minutes. The comparison of the
      postoperative computed tomography scans with the preoperative planning showed
      good accuracy of the instrument with a mean deviation of the catheter tips from
      the planned position of 1.5 mm (range 1.0-2.1 mm). CONCLUSION: The new tool
      allows safe and quick placement of ventricular catheters. The adjustment of the
      tool to the planned trajectory is performed before catheter insertion and allows
      optimal concentration on the insertion procedure and the fingertip feeling for
      the penetrated tissue.

PMID- 20679939
TI  - Naming the soft tissue layers of the temporoparietal region: unifying anatomic
      terminology across surgical disciplines.
AB  - BACKGROUND: The complexity of temporoparietal anatomy is compounded by
      inconsistent nomenclature. OBJECTIVE: To provide a comprehensive review of the
      variations in terminology and anatomic descriptions of the temporoparietal soft
      tissue layers, with the aim of improving learning and communication across
      surgical disciplines. METHODS: MEDLINE (1950-2009) searches were conducted for
      anatomic studies of the temporoparietal region, and for studies describing
      temporoparietal anatomy in the context of surgical techniques. RESULTS: Sixty
      nine articles were included in the review. Naming of the soft tissue layers of
      the temporoparietal region was inconsistent both within and across surgical
      disciplines, with several terms utilized for the same layer and occasionally the
      same term applied to different layers. Studies also varied in their description
      of the vascular, neural, and soft tissue architecture of the temporoparietal
      region. CONCLUSION: A uniform, descriptive nomenclature is paramount to
      facilitating surgical education and interpreting future studies. A naming system
      based on the Terminologica Anatomica is proposed in this review. From superficial
      to deep, the proposed terms for the soft tissue layers of the temporoparietal
      region include: temporoparietal fascia, loose areolar tissue plane, superficial
      leaflet of temporal fascia, fat pad of temporal fascia, deep leaflet of temporal
      fascia, fat pad deep to temporal fascia, temporalis or temporal muscle, and
      pericranium.

PMID- 20679940
TI  - Optic canal involvement in tuberculum sellae meningiomas: influence on approach,
      recurrence, and visual recovery.
AB  - BACKGROUND: Tuberculum sellae meningiomas frequently extend into the optic
      canals. OBJECTIVE: To emphasize the high frequency of optic canal (OC)
      involvement in tuberculum sellae meningiomas; the importance of opening the OC
      and of removing tumor within the canal; and the effect of this maneuver on visual
      outcome, recurrence rates, and surgical approach selection. METHODS: A
      retrospective review of 58 patients with tuberculum sellae meningiomas treated
      surgically by the senior author (O.A.M) between 1993 and 2009 was performed. The
      frequency of involvement of the OC was documented, as well as the impact of
      removal of this part of the tumor on visual outcome and recurrence. RESULTS:
      Total resection (Simpson grade 1) was achieved in 51 of 58 patients (87.9%). The
      tumor invaded the optic canal in 67%. Tumor resection from the optic nerve was
      achieved in all cases, and most (92%) underwent deroofing of the OC for this
      purpose. The dura over the tuberculum sella and/or planum sphenoidale was removed
      in all patients. Eighty-three percent required removal of affected hyperostotic
      bone. Vision was improved and/or spared in 88%. The average follow-up period was
      23 months with 1 recurrence detected. CONCLUSION: In the majority of cases,
      tuberculum sellae meningiomas extend into 1 or both OCs. Opening the OC for
      resection of the intracanalicular portion of the tumor enabled us to achieve
      excellent visual outcome. The supraorbital craniotomy remains the favored
      approach for removal of such tumors because it allows unroofing of both OCs, wide
      excision of the dura, and drilling of the affected bone.

PMID- 20679941
TI  - The utility of using the bispectral index-Vista for detecting cross-clamping
      decline in cerebral blood flow velocity.
AB  - BACKGROUND: Patients undergoing carotid endarterectomy for extracranial internal
      carotid artery stenosis are at risk of cerebral ischemia/hypoperfusion. Criterion
      recommended by European and American committees to determine whether to place a
      shunt consisted of a decline in transcranial Doppler ultrasonography-measured
      middle cerebral artery blood flow velocity (MCBFV) to < 30% to 40% of
      intraoperative preclamp value. OBJECTIVE: To assess the discriminative power of
      the bispectral index (BIS)-Vista monitor for detecting a 40% decline in MCBFV
      with cross-clamping. METHODS: In 20 patients undergoing carotid endarterectomy
      under remifentanil/propofol anesthesia, BIS-Vista data, MCBFV, and pulsatility
      index from bilaterally mounted BIS-Vista and transcranial Doppler monitors were
      continuously recorded. RESULTS: Coefficient of determination revealed good
      correlation (r = 0.763) between ipsilateral BIS-Vista and MCBFV after cross
      clamping. BIS-Vista exhibited a high discriminative power of 0.850 (95%
      confidence interval, 0.455-0.966) area under the receiver-operating
      characteristic curve in detecting an ipsilateral 40% MCBFV decline. Two-way
      analysis of variance (location by time) suggests that BIS-Vista exhibited a
      global decline; ie, both BIS-Vistas declined when 1 carotid on either side was
      clamped because there was no significant interhemispheric difference (P = .112)
      in mean BIS-Vista values over time. CONCLUSION: Although we demonstrated good
      correlation and high discriminative power of the BIS-Vista monitor in depicting a
      MCBFV decline that could serve as indicator of decline in cerebral activity, BIS
      Vista cannot be considered a reliable indicator of cerebral
      ischemia/hypoperfusion that could replace transcranial Doppler monitoring to
      determine whether a shunt is to be placed.

PMID- 20679942
TI  - A nonradiographic system for assessing pressure for the Codman-Hakim Programmable
      Valve.
AB  - BACKGROUND: The Codman-Hakim Programmable Valve is widely used in shunting
      hydrocephalus and other conditions. OBJECT: To establish an accurate valve
      verification system for the Codman-Hakim programmable valve that does not require
      radiographic exposure. METHODS: Prospective clinical trial tested a new valve
      verification system at 9 research sites. RESULTS: The Valve Programming and
      Verification System allowed us to establish the valve setting in 62% of subjects
      with a programmable valve. CONCLUSION: The Valve Programming and Verification
      System avoids radiation exposure, is cost-effective, and time efficient for the
      patient and provider. In approximately one third of subjects, those in whom
      "adjustment complete" is not achieved, cranial radiographs are still needed.

PMID- 20679943
TI  - A modified technique for dowel fibular strut graft placement and circumferential
      fusion in the setting of L5-S1 spondylolisthesis and multilevel degenerative disc
      disease.
AB  - BACKGROUND: Traditional techniques for the treatment of isthmic spondylolisthesis
      pass a fibular dowel graft across the L5-S1 disc by using the anterior portion of
      the L5 body. OBJECTIVE: To introduce a technique for the treatment of isthmic
      spondylolisthesis in the setting of multilevel degenerative disc disease in
      adults. Our modified technique allows us to traverse the L5-S1 disc via the L4-5
      disc space thereby treating the degenerated disc at L4-5 simultaneously. METHODS:
      A standard anterior discectomy was performed on L4-5. Using biplanar fluoroscopy,
      a Kirschner wire was placed beginning at the anterior third of the L5 superior
      endplate and ending at S1. An anterior cruciate ligament reamer was used to make
      a channel for the fibular allograft. Then, a femoral ring allograft was placed in
      the disc space at L4-5, and standard anterior lumbar interbody fusions were
      performed at any additional cephalad level(s). Afterward, posterior instrumented
      fusion was performed to complement the anterior fusion procedure (except at L5),
      and wide decompression followed. RESULTS: All patients presented with isthmic
      spondylolisthesis and all had multilevel fusions. The mean slip angle was 32.6
      degrees (37.8 degrees preoperatively), and mean lumbar index was 67%. After the
      procedure, the average endplate-to-dowel angle was 107.1 degrees compared with
      134 degrees. All patients had clinical and radiographic evidence of solid fusion
      without the need for revisions. CONCLUSION: The proposed advantage of our
      modified technique is twofold. The graft is placed nearly perpendicular to the L5
      S1 interface, as it will behave more efficiently with respect to interfragmental
      compression. Also, surgeons gain access to fuse L4-5 anteriorly and posteriorly.

PMID- 20679944
TI  - Accuracy validation in a cadaver model of cranial neuronavigation using a surface
      autoregistration mask.
AB  - BACKGROUND: Image guidance systems are widely used in neurosurgical practice.
      OBJECTIVE: To compare the operational accuracy of a neuronavigation system when
      registration was accomplished with a commercially available surface-based
      autoregistration system vs other fiducial-based registrations. METHODS: We
      evaluated the operational accuracy of different registration methods in 20
      cadaveric heads. Every specimen was prepared with 10 titanium microscrews
      functioning as external/internal targets and as bone fiducials. Six scalp
      fiducials were also affixed to each specimen that was registered with bone, scalp
      fiducials, and the autoregistration mask. The coordinates of all the target
      points were measured, first manually on the screen of the navigation system and
      then by touching the head of the implanted screw on the specimen. The difference
      between the real and virtual coordinates was calculated. RESULTS: Means of the
      differences for external anterior targets were 1.96, 3.12, and 3.20 mm and 1.95,
      3.24, and 3.19 mm for external posterior targets for the bone fiducials, adhesive
      fiducials, and autoregistration mask, respectively. Means of the differences for
      internal anterior targets were 2.60, 3.65, and 2.16 mm and 2.91, 3.83, and 2.41
      mm for internal posterior targets for the bone fiducials, adhesive fiducials, and
      autoregistration mask, respectively. CONCLUSION: Bone fiducial registration is
      associated with a statistically greater operational accuracy than scalp adhesive
      fiducials and the autoregistration mask in reaching anterior and posterior
      external targets (P < .001). Registration accomplished with the autoregistration
      mask is associated with a statistically greater operational accuracy in reaching
      internal targets than adhesive fiducials registration (P < .001) or bone
      fiducials registration (P < .05 and P < .01 for anterior and posterior targets,
      respectively).

PMID- 20679945
TI  - Brain surgery in a stereoscopic virtual reality environment: a single
      institution's experience with 100 cases.
AB  - BACKGROUND: A comprehensive understanding of the spatial relationships between
      intracranial anatomy and pathological features is a crucial element in
      neurosurgical planning. OBJECT: To assess our clinical experiences using a novel
      approach, stereoscopic virtual reality environment, to help neurosurgeons with
      both surgical training and surgical strategic planning purposes. METHODS: Patient
      specific digital imaging data obtained from a variety of different diagnostic
      sources (computed tomography, computed tomographic angiography, magnetic
      resonance, functional magnetic resonance, magnetic resonance-diffusion tensor
      imaging) were collected and then transferred to a workstation setting. These
      clinical data were obtained from 100 patients who were suffering from either
      brain vascular malformations or tumors that were located in difficult brain
      sites. A 3-dimensional volume rendering was produced for each of the 100 clinical
      cases, which were then subjected to data coregistration and fusion. RESULTS: By
      using different head positioning systems and craniotomy options, we simulated
      microscopic visualizations of the lesion through numerous surgical approaches and
      from various angles of view. This simulation strategy enabled us to carry out an
      approach selection and eventually to identify the optimum angle of lesion
      visualization. CONCLUSION: These virtual craniotomies successfully simulated a
      sampling of different operative environments that have the potential to play a
      significant role in neurosurgical training and operative planning worthy of
      further exploration and development.

PMID- 20679946
TI  - Peroneal and tibial intraneural ganglion cysts in the knee region: a technical
      note.
AB  - BACKGROUND: Recent research has resulted in an improved understanding of the
      pathogenesis and treatment of intraneural ganglia, particularly with respect to
      the most common form, the peroneal nerve at the fibular neck region. OBJECTIVE:
      To outline the mechanism for the development and propagation of intraneural
      ganglia located in the knee region, along with their treatment, as well as
      highlight how shared principles can be exploited for successful treatment of the
      more commonly occurring peroneal intraneural ganglia. METHODS: A surgical
      approach has been developed for peroneal intraneural cysts based on the
      pathogenesis. The treatment of the less common tibial intraneural cysts is
      designed along the same principles. RESULTS: A strategy consisting of (1)
      disarticulation (resection) of the superior tibiofibular joint (ie, the source),
      (2) disconnection of the articular branch connection (ie, the conduit), and (3)
      decompression (rather than resection) of the cyst has improved outcomes and
      eliminated intraneural recurrences in peroneal intraneural cysts. These same
      principles and techniques can be applied to the rarer tibial intraneural ganglia
      derived from the same joint. The mechanism of development and propagation for
      intraneural cysts in the knee region as well as a surgical technique and its
      rational are described and illustrated. CONCLUSION: Understanding the joint
      related basis of intraneural cysts leads to simple targeted surgery that
      addresses the joint, its articular branch, and the cyst. The success of the
      shared surgical strategy for both peroneal and tibial intraneural ganglia
      confirms the principles of the unifying articular theory.

PMID- 20679947
TI  - Management of anterolateral foramen magnum meningiomas: surgical vs conservative
      decision making.
AB  - BACKGROUND: Anterolateral meningiomas of the foramen magnum (FMMs) represent a
      neurosurgical challenge because they grow in close contact with osteoarticular,
      nervous, and vascular structures that cannot be sacrificed or retracted.
      OBJECTIVE: To evaluate our strategy and results in 26 patients with FMMs and
      analyze factors affecting the decision-making process, resection, and outcome.
      METHODS: Among 26 consecutive symptomatic FMM (10 anterior, 16 lateral) patients
      (16 women, 10 men, ages 28-82 years), 4 older than 70 years of age were
      untreated. Twenty-two were operated on using a posterolateral approach, with the
      vertebral artery transposed in 19 and the occipital condyle drilled in 10. We
      analyzed the characteristics and outcome of untreated cases, the utility of THE
      occipital condyle drilled, the difficulties of microdissection, morbidity and
      total removal rates, the outcome of tumor residues, and the literature on
      radiosurgery. RESULTS: Three of 4 untreated patients remained clinically stable
      at 2 to 5 years. After systematic vertebral artery medial transposition and
      occipital condyle drilled in 6 cases, our technique evolved with experience in
      the next 16 (vertebral artery transposed in 13 of 16; occipital condyle drilled
      in 4 of 13) for dissecting anteriorly beyond midline (anterior FMMs).
      Retrocondylar access was sufficient for lateral FMMs. Tumors were totally removed
      in 16 of 22 (73%). One patient died, and 4 had permanent deficits. Follow-up of
      more than 5 years in 12 patients showed no C0-1 instability, and slight increase
      of tumor residue size 7 years after surgery. In the literature, 15 FMMs treated
      with radiosurgery are reported, 13 at diagnosis and 2 at recurrence, with short
      term clinical and radiological safety and efficacy. CONCLUSION: We currently
      recommend (1) aiming for subtotal removal in difficult cases, (2) remaining
      conservative in asymptomatic or elderly patients with mild symptoms, and (3)
      considering radiosurgery at diagnosis for small (<30 mm) symptomatic FMMs or as
      an adjunct for evolving residues/recurrences in poor candidates for resection.

PMID- 20679948
TI  - A simple technique for interventional tool placement combining fluoroscopy with
      interventional computed tomography on a C-arm system.
AB  - BACKGROUND: Flat-panel cone-beam computed tomography (FP-CBCT) has recently been
      introduced as a clinical feature in neuroangiography radiographic C-arm systems.
      OBJECTIVE: To introduce a method of positioning a surgical tool such as a needle
      or ablation probe within a target specified by intraoperative FP-CBCT scanning.
      METHODS: Two human cadaver and 2 porcine cadaver heads were injected with a
      mixture of silicone and contrast agent to simulate a contrast-enhanced tumor.
      Preoperative imaging was performed using a standard 1.5-T magnetic resonance
      imaging scanner. Intraoperative imaging was used to define the needle trajectory
      on a GE Innova 4100 flat panel-based neuroangiography C-arm system. RESULTS:
      Using a combination of FP-CBCT and fluoroscopy, a needle was successfully
      positioned within each of the simulated contrast-enhanced tumors, as verified by
      subsequent FP-CBCT scans. CONCLUSIONS: This proof-of-concept study demonstrates
      the potential utility of combining FP-CBCT scanning with fluoroscopy to position
      surgical tools when stereotactic devices and image-guided surgery systems are not
      available. However, further work is required to fully characterize the precision
      and accuracy of the method in a variety of realistic surgical sites.

PMID- 20679949
TI  - Extradural endoscope-assisted subtemporal posterior clinoidectomy: a cadaver
      investigation study.
AB  - BACKGROUND: Surgical treatment of distal basilar artery aneurysms is challenging
      because of the narrow surgical corridor, presence of vital perforating vessels,
      deep location, and difficulty in obtaining proximal control. OBJECTIVE: To
      investigate using a cadaver model the feasibility of performing a transcranial
      extradural posterior clinoidectomy via a subtemporal route between V2 and V3
      using an endoscope-microscope combination. METHODS: Fourteen dissections were
      performed in 14 fresh cadaver heads. A standard pterional approach with removal
      of the zygomatic arch was followed by a 2-stage dissection to remove the
      posterior clinoid process. In stage 1 (microscopic stage), the area between the
      second and third trigeminal divisions (V2 and V3) was exposed and the anterior
      half of the bone between them was drilled to the sphenoid sinus cavity inferior
      to the carotid sulcus. In stage 2 (endoscopic stage), the drilling was continued
      to the carotid sulcus. Next, the endosteal layer of the dura lining the carotid
      sulcus was dissected from the bone that was then removed. At the end of this
      stage, the dura reflection that forms the posterior part of the pituitary capsule
      was exposed and the base of the posterior clinoid process was removed using a
      high-speed drill and curet. Finally, the dura was opened to confirm the removal
      of the posterior clinoid process. RESULTS: It was possible to remove the
      posterior clinoid process in every specimen without any obvious anatomic injury
      to the surrounding structures. CONCLUSION: This study demonstrated the
      feasibility of the resection of the posterior clinoid process extradurally. This
      maneuver could be incorporated in multiple cranial base approaches to the
      retrosellar area and interpeduncular cistern region.

PMID- 20679950
TI  - Anterolateral C1-C2 transarticular fixation for atlantoaxial arthrodesis:
      landmarks, working area, and angles of approach.
AB  - BACKGROUND: An alternative route must be used for atlantoaxial arthrodesis to
      avoid the risks of transoral route or when posterior approaches are
      contraindicated. OBJECTIVE: To assess relevant quantitative anatomic parameters
      for C1-C2 anterolateral transarticular fixation and to demonstrate the nuances of
      an anterolateral approach to the upper cervical spine. METHODS: Five cadaveric
      necks were dissected bilaterally to demonstrate anatomic landmarks and surgical
      technique. The C2 pars interarticularis was used as the entry for inserting
      screws toward the C1 lateral mass. Ten computed tomography scans were analyzed to
      quantify working area and optimal angles of approach. RESULTS: The medial surface
      of sternocleidomastoid muscle was dissected extensively but not divided. The C2
      transverse process was a landmark for guiding dissection posterior to the carotid
      sheath. In all specimens, the gray ramus communicans from the superior cervical
      ganglion to the C2 nerve was a landmark for locating the C2 pars. Slightly below
      that branch, the longus capitis muscle could be displaced medially to reach the
      C2 pars. The ideal angles for screw placement were 22.9 +/- 5.7 degrees medial to
      the sagittal plane and 25.3 +/- 7.4 degrees posterior to the coronal plane. The
      mean working area was 71.2 mm (range, 49-103 mm). CONCLUSION: We propose a new
      anterolateral stabilization technique for atlantoaxial instability based on less
      traumatic dissection of the upper cervical region, different instrumentation, and
      guidance by reliable landmarks. For anterolateral transarticular C1-C2 screw
      fixation, the gray ramus communicans to the C2 nerve is a reliable landmark for
      locating the entry for a screw on the C2 pars.

PMID- 20679951
TI  - Endoscopic assistance in the epidural subtemporal approach and Kawase approach:
      anatomic study.
AB  - BACKGROUND: Few reports exist in the literature about the use of endoscope
      assistance in the identification of structures in the posterior fossa. OBJECTIVE:
      To asses the advantage of endoscopic assistance in the epidural subtemporal and
      Kawase approaches by studying anatomic exposure and surgical freedom in the
      posterior cranial fossa. METHODS: Twelve epidural subtemporal approaches were
      performed on 6 adult cadaveric heads. On the same specimens, 6 endoscope-assisted
      subtemporal approaches and 6 Kawase approaches were then performed. At the end of
      each Kawase approach, endoscope assistance was used. The microsurgical
      observations were performed with a surgical microscope with magnification ranging
      from 4 x to 40 x. Endoscopic observations were made with a 0 degrees , 4-mm rod
      lens endoscope. Anatomic exposure and surgical freedom were analyzed. RESULTS:
      Endoscopic assistance during the epidural subtemporal approach increased the
      anatomic exposure 3 mm superiorly, 20 mm inferiorly, and 10 mm medially from the
      trigeminal nerve. Surgical freedom was limited in the temporal lobe, the petrous
      apex, and the trigeminal nerve. The amount of increased anatomic exposure
      obtained with endoscopic assistance during the Kawase approach was 26 mm
      inferiorly and medially from the trigeminal nerve. Surgical freedom was limited
      by the brainstem and the depth of the posterior cranial fossa. CONCLUSION: The
      endoscope-assisted subtemporal approach can be useful in visualizing tumor in the
      posterior fossa. It can help the surgeon in planning further surgical steps
      through consideration of the size, extension, and adherence of the tumor to
      surrounding structures. The endoscope-assisted Kawase approach permits maximum
      anatomic exposure of the posterior cranial fossa, although the deepest
      neurovascular structures could be better addressed with more direct approaches.

PMID- 20679952
TI  - Transorbital neuroendoscopic surgery.
AB  - BACKGROUND: Transorbital neuroendoscopic surgery (TONES) pathways attempt to
      address some of the technical challenges of accessing laterally placed anterior
      skull base lesions or paramedian lesions that cross neurovascular structures.
      TONES approaches allow simultaneous coplanar visualization and working space
      above and below the skull base. OBJECTIVE: To present an anatomic study, a
      description of the surgical techniques, and an analysis of the safety and
      efficacy of 20 consecutive procedures using TONES for a variety of pathological
      conditions. METHODS: Sixteen patients underwent 20 TONES procedures for anterior
      skull base pathology, including repair of cerebrospinal leak, optic nerve
      decompression, repair of cranial base fractures, and removal of 3 skull base
      tumors. Ten patients were male, and 6 were female. The mean age at presentation
      was 44 years. Follow-up was 6 to 18 months with a mean of 9 months. RESULTS:
      There were no significant complications or treatment failures in any of the 20
      procedures. A variety of pathological conditions were treated, including
      cerebrospinal fluid leaks, fractures, mass lesions, and tumors. The TONES
      approach provided up to 4 separate access ports with ample exposure for
      manipulation and correction of the pathology. CONCLUSION: This anatomic and
      prospective outcome study demonstrates that TONES provides safe and effective
      coplanar endoscopic access to the anterior and middle cranial base. These novel
      TONES approaches may be added to the wide range of published minimally invasive
      armamentarium when approaching challenging skull base pathology.

PMID- 20679953
TI  - Dural entrance of the bridging vein in the middle cranial fossa: a novel
      classification of the cerebral veins for preoperative planning.
AB  - BACKGROUND AND IMPORTANCE: Understanding of the intracranial venous anatomy is
      essential for preoperative planning. OBJECTIVE: To identify anatomic features of
      the dural entrance of the bridging veins (BVs) into the dural sinuses in the
      middle cranial fossa on the cadaver and to correlate such features with those of
      digital subtraction venogram, computed tomographic venogram, and magnetic
      resonance venogram. CLINICAL PRESENTATION: A total of 30 adult cadavers and 86
      patients were examined with anatomic dissection or neuroimages. The number,
      diameter, and location of the BVs entering the dural sinuses in the middle
      cranial fossa were recorded and compared between the cadavers and neuroimages.
      The dural entrances of the BVs were identifiable on neuroimages and distributed
      mainly at the anteromedial area of the fossa. Morphological features of the dural
      sinuses and meningeal veins in the fossa indicated that the techniques of
      lengthening the BV by dissecting it away from the dura mater or cutting a small
      area of the dura along the sides of the BV may not be applicable for the
      management of BVs in the anteromedial middle cranial fossa. CONCLUSION: Unique
      anatomic features of the dural entrance of BVs entering the dural sinuses in the
      cadaver are correlated to those on neuroimages. Identification of the dural
      entrance of BVs with neuroimaging modalities provides a reliable measure for
      preoperative planning.

PMID- 20679954
TI  - Fully endoscopic transnasal approach to the jugular foramen: anatomic study and
      clinical considerations.
AB  - BACKGROUND AND IMPORTANCE: To describe a transnasal endoscopic route to the
      jugular foramen and the endoscopic anatomy of the infratemporal fossa. CLINICAL
      PRESENTATION: Endoscopic transnasal dissection of the infratemporal fossa was
      performed in 3 injected fresh heads (1 head only in arteries and 2 heads in
      arteries and veins). Two other double-injected specimens were dissected
      externally (2 of them side laterally and 1 anteriorly) to compare the different
      views and better understand the 3-dimensionality of the region.Detailed
      endoscopic anatomy of the infratemporal fossa was clearly observed. The
      realization of a septal and posterior maxillary window allows surgeons to gain
      space to the jugular foramen. The ability to manage the vessels, especially the
      veins, and identify the muscles is mandatory. The fundamental role of the vidian
      canal in targeting the anterior genu of the internal carotid artery is confirmed.
      The role of the maxillary and mandibular branches of the trigeminal nerve and the
      eustachian tube in this kind of approach is critical. CONCLUSION: A fully
      transnasal endoscopic route to the jugular foramen is feasible. The most
      important landmark for this kind of approach is the eustachian tube.

PMID- 20679955
TI  - Long-term hearing preservation after microsurgical excision of vestibular
      schwannoma.
AB  - OBJECTIVE: To examine long-term hearing outcomes after microsurgical excision of
      vestibular schwannoma (VS). STUDY DESIGN: Retrospective case review. SETTING:
      Tertiary referral center. PATIENTS: Forty-nine subjects at a single institution
      who had undergone microsurgical excision of a VS via middle cranial fossa (MCF)
      approach between 1994 and 2007 with immediate postoperative (PO) hearing
      preservation and for whom long-term audiograms were available. INTERVENTION:
      Diagnostic. MAIN OUTCOME MEASURES: Word Recognition Score (WRS) is defined by
      speech discrimination scores (SDS) greater than 70% (grade I), 50% to 70% (grade
      II), less than 50% (grade III), and 0% (grade IV). RESULTS: For subjects with
      more than 2 years of follow-up, WRS I hearing was present PO in 42 of 49 patients
      and was preserved at the latest follow-up in 38 (90%) of 42 patients. No subjects
      fell beyond WRS II. WRS I hearing was maintained in 23 (88%) of 26 patients with
      more than 5 years of follow-up. Postoperative WRS I to II hearing was maintained
      in 28 (96%) of 29 patients with more than 5 years of follow-up. The patient who
      lost significant hearing in the ear operated on had sensorineural hearing loss
      that paralleled deterioration in her ear that was not operated on. CONCLUSION:
      Most subjects maintain their initial PO SDS after microsurgical VS removal, and
      therefore, the initial PO WRS is predictive of long-term hearing. Postsurgical
      changes do not alter the natural rate or pattern of progressive bilateral
      sensorineural hearing loss in individual subjects.

PMID- 20679956
TI  - Aural symptoms in patients with temporomandibular joint disorders: multiple
      frequency tympanometry provides objective evidence of changes in middle ear
      impedance.
AB  - OBJECTIVE: The association of temporomandibular joint (TMJ) disorders with aural
      symptoms, such as tinnitus, otic fullness, and subjective decrease of hearing
      acuity, is a well-established clinical observation. Although several hypotheses
      have been made about the otic-conductive origin of these complaints, conventional
      226-Hz tympanometry has failed to demonstrate any middle ear abnormalities. The
      aim of this study was to evaluate patients with TMJ disorders with multiple
      frequency tympanometry (MFT). STUDY DESIGN: Prospective clinical study. SETTING:
      Outpatient clinic. PATIENTS: The population of this study consisted of 40
      patients with unilateral TMJ disorders diagnosed for longer than 1 month.
      INTERVENTIONS: After verifying that there were no abnormal otoscopic findings,
      226-Hz tympanometry, conventional pure-tone audiometry, brainstem auditory evoked
      potentials, and MFT were performed. MAIN OUTCOME MEASURE: Resonant frequency (RF)
      values. RESULTS: With the exception of MFT, no abnormal audiologic findings were
      revealed. The ear ipsilateral to the lesion demonstrated significantly higher (p
      = 0.002) RF values in comparison to the contralateral ear. The difference in RF
      values was more obvious in patients aged 45 years or younger. CONCLUSION: The
      results of this study imply an increase in the stiffness of the middle ear, which
      has not been detected by conventional tympanometry. This represents the first
      concrete documentation of minor alterations in the conductive properties of the
      middle ear and seems to support the various hypotheses on the middle-ear origin
      of aural complaints in patients with TMJ disorders. Further studies are needed
      before a clear insight on the presumably multifactorial pathophysiology of these
      complaints can finally be reached.

PMID- 20679957
TI  - Active middle ear implant application in case of stapes fixation: a temporal bone
      study.
AB  - HYPOTHESIS: Driving the oval window directly with an active middle ear implant
      (AMEI) can produce high levels of input to the inner ear. BACKGROUND: Treatment
      of otosclerosis bypasses the stapes with a piston that penetrates the vestibule.
      Although this treats the conductive component of hearing loss, it does not treat
      the sensorineural part, which can be improved using an additional conventional
      hearing aid. Active middle ear implants have been proposed to be an alternative
      in treating otosclerosis in cases of mixed hearing losses. METHODS: Seven
      temporal bones were prepared to expose the stapes and round window (RW). Stapes
      and RW velocities were measured while driving with an AMEI the stapes head with a
      bell-shaped tip. The stapes footplate was then fixed with acrylic cement;
      fixation was confirmed through attenuated RW velocities. A cylinder tip (0.5 mm)
      was then used to drive the inner ear through a stapedotomy with and without
      interposition of fascia. RESULTS: Driving the stapes with an AMEI produced mean
      maximum equivalent ear canal sound pressure levels (SPL) of 138 dB (0.25-8 kHz at
      1 V [RMS]). Stapes fixation caused a approximately 25-dB attenuation. Driving
      with a cylinder tip through the stapedotomy produced 114 dB SPL (24 dB less than
      normal) and 110 dB SPL (28 dB less than normal) performance with and without
      fascia, respectively. Performance with fascia was greater than without.
      CONCLUSION: Driving the oval window with an AMEI in a scenario of stapes fixation
      was demonstrated to be feasible, with performance comparable to traditional AMEI
      coupling to the incus or stapes. These possibilities offer new perspectives to
      treat mixed hearing loss in case of fixed footplate.

PMID- 20679958
TI  - Paracrine loops of keratinocyte stimulation in cholesteatoma tissue: an
      immunofluorescence, transmission electron microscopy, and molecular study.
AB  - HYPOTHESIS: In relation to the keratinocyte growth factor (KGF) expression in
      cholesteatoma tissue, the inflammatory infiltrate present in this disease could
      play a relevant role in the paracrine stimulation of keratinocytes. BACKGROUND:
      Cholesteatoma is a temporal bone pathologic disease characterized by active
      proliferation of epithelial cells, with progressive growth and involvement of the
      neighboring middle/inner ear structures. The pathogenetic mechanism underlying
      the hyperproliferation of keratinocytes is not yet fully clarified. It has been
      suggested that keratinocyte proliferation and migration could be mediated by
      several autocrine and paracrine growth factors and their receptors. A previous
      study has reported that the expression of KGF receptor is increased in more
      differentiated areas of the cholesteatoma tissue, whereas the expression of the
      epidermal growth factor receptor is associated with proliferative and migratory
      areas of the lesion. METHODS: Fresh cholesteatoma samples were collected during
      surgical procedures. Serial cryosections were examined by conventional
      hematoxylin and eosin or by immunofluorescence with antipancytokeratin
      antibodies. The ultrastructural features were analyzed by transmission electron
      microscopy. The expression of KGF, K1, and filaggrin in the samples was evaluated
      by quantitative reverse transcription-polymerase chain reaction and correlated
      with the dermal degree of inflammatory infiltrate and the presence of stromal
      cells. RESULTS: Increased expression of KGF was associated with strong levels of
      the inflammatory infiltrate. CONCLUSION: These results would suggest that KGF up
      modulation is a consequence of fibroblast stimulation by inflammatory cells and
      that this paracrine loop could be responsible not only for the hyperproliferation
      of keratinocytes in cholesteatoma tissue but also for the deregulation of
      epidermal differentiation.

PMID- 20679959
TI  - Intraoperative neural response telemetry as a predictor of performance.
AB  - OBJECTIVE: To determine whether intraoperative neural response telemetry (tNRT)
      is predictive of postoperative speech perception. STUDY DESIGN: Retrospective
      review. SETTING: Tertiary referral center. PATIENTS: Children (n = 24) aged
      between 5 and 17 years and adults 18 years and older (n = 73) with severe-to
      profound hearing loss and implanted with the Nucleus Freedom device between 2005
      and 2008 and observed at least 1 year were included. INTERVENTION: Intraoperative
      neural response telemetry after insertion of the electrode array. MAIN OUTCOME
      MEASURE: Measures included 1) intraoperative tNRT measurements and 2)
      preoperative and 1-year postoperative open-set word recognition scores using age
      appropriate open-set tests for children and adults. Intraoperative neural
      response telemetry levels for electrodes E20, E15, E10, and E5 in each patient
      were correlated to performance at the 1-year evaluation interval. RESULTS: No
      correlation existed between tNRT responses and open-set speech performance at the
      1-year evaluation. Several patients had absent tNRT in the OR but developed
      speech recognition abilities, whereas the remaining patients had intraoperative
      responses with levels of postoperative performance ranging from 0% to 100%.
      CONCLUSION: This study suggests that there is no significant correlation between
      intraoperative tNRT and speech perception performance at 1 year. At the time of
      surgery, tNRT provides valuable information regarding the electrical output of
      the implant and the response of the auditory system to electrical stimulation and
      preliminary device programming data; however, it is not a valuable predictor of
      postoperative performance. Furthermore, the absence of tNRT does not necessarily
      indicate a lack of stimulation.

PMID- 20679960
TI  - Pharmacogenetic analysis of lipid responses to rosuvastatin in Chinese patients.
AB  - Lipid changes with statin treatments vary greatly between individuals for reasons
      which are largely unknown. This study was performed to examine the genetic
      determinants of lipid responses to rosuvastatin in Chinese patients. A total of
      125 polymorphisms in 61 candidate genes from 386 Chinese patients were analyzed
      for association with the lipid responses to rosuvastatin 10 mg daily. The
      polymorphisms most highly associated with the low-density lipoprotein cholesterol
      (LDL-C) response were 421C>A in the ATP-binding cassette G2 gene (P=9.2*10),
      followed by 18281G>A (V257M) in the flavin-containing monooxygenase 3 gene
      (P=0.0002), 1421C>G in the lipoprotein lipase gene (P=0.002), and rs4420638 in
      the apolipoprotein E/C-I/C-IV/C-II gene cluster (P=0.004). Patients with familial
      hypercholesterolemia had 2.6% smaller reductions in LDL-C compared with patients
      without familial hypercholesterolemia. This study identified some genetic
      determinants of LDL-C response to rosuvastatin in Chinese patients, which need to
      be replicated in other populations.

PMID- 20679961
TI  - Development of new HLA-B*3505 genotyping method using Invader assay.
AB  - Several pharmacogenetic studies have revealed strong associations between
      specific human leukocyte antigen (HLA) alleles and the susceptibility to drug
      hypersensitivity. Recently, we reported HLA-B*3505 as a strong genetic biomarker
      for the nevirapine-induced skin rash in Thai population. Here, we developed a new
      HLA-B*3505 genotyping method by a combination of the Universal Invader assay and
      sequence-specific primer PCR. From the sequence alignment of 68 HLA-B alleles in
      the Thai population, we selected the two most discriminative SNPs (rs1140412 and
      rs4997052) as target SNP sites. When we carried out the assay using 324 Thai
      individuals, fluorescence intensities of HLA-B*3505-positive and HLA-B*3505
      negative samples were apparently discriminated at the endpoint of the reaction.
      Our results were 100% concordant with those obtained by a sequence-based typing
      method. As our assay is simple and rapid, we believe our method will be a useful
      tool for pharmacogenetic testing of the nevirapine-induced skin rash.

PMID- 20679962
TI  - Polymorphisms in type I and II inosine monophosphate dehydrogenase genes and
      association with clinical outcome in patients on mycophenolate mofetil.
AB  - BACKGROUND: Type I and II inosine monophosphate dehydrogenases (IMPDH) are the
      targets of mycophenolic acid (MPA), a widely used immunosuppressant. The aims of
      this study were: to check the presence of controversial polymorphisms in the
      IMPDH II gene; to look for new ones; and to investigate potential associations
      between the most frequent SNPs in both IMPDH genes and clinical outcome in renal
      transplant recipients. METHODS: The DNA and clinical data of 456 patients from
      two clinical trials were collected. We sequenced the IMPDH II gene in 80 patients
      and we genotyped the 456 patients' DNA for the IMPDH II rs4974081, rs11706052,
      787C>T and the IMPDH I rs2278293 and rs2278294 SNPs, all of which were earlier
      reported to be potentially involved in MPA treatment related outcome. We
      investigated the associations of biopsy proven acute rejection (BPAR),
      leucopenia, cytomegalovirus infections and other infections with these IMPDH
      polymorphisms, as well as with demographic, biological and treatment data using
      multivariate analysis. RESULTS: Many IMPDH II variant alleles referenced in
      Genbank were not detected and no new polymorphisms were identified. In the whole
      group of 456 patients, the IMPDH I rs2278294 SNP was associated with a lower risk
      of BPAR and a higher risk of leucopenia over the first year post-transplantation.
      No other IMPDH I or IMPDH II polymorphism was significantly associated with any
      clinical outcome. Interestingly, calcineurin inhibitor and MPA exposures below
      the therapeutic range increased the risk of BPAR. Cytomegalovirus infection was
      the factor most closely linked with leucopenia, whereas tacrolimus was associated
      with fewer infections than cyclosporine. CONCLUSION: IMPDH II genotyping may not
      improve MPA treatment outcome over the first year post-transplantation, in
      contrast to MPA and calcineurine inhibitor therapeutic drug monitoring and IMPDH
      I genotyping.

PMID- 20679963
TI  - Comprehensive assessment of sociodemographic and behavioral risk factors for
      Mycoplasma genitalium infection in women.
AB  - BACKGROUND: Neisseria gonorrhoeae and Chlamydia trachomatis are characterized by
      different risk factors, thus control strategies for each also differ. In
      contrast, risk factors for Mycoplasma genitalium have not been well
      characterized. METHODS: Between 2000 and 2006, 1090 women ages 14 to 45 attending
      the Public Health-Seattle & King County Sexually Transmitted Diseases Clinic in
      Seattle, WA, underwent clinical examination and computer-assisted survey
      interview. M. genitalium was detected by transcription mediated amplification
      from self-obtained vaginal swab specimens. C. trachomatis and N. gonorrhoeae were
      detected by culture from cervical swab specimens. RESULTS: Prevalent M.
      genitalium infection was detected in 84 women (7.7%), C. trachomatis in 63
      (5.8%), and N. gonorrhoeae in 26 (2.4%). Age <20 and nonwhite race were
      associated with increased risk for all 3 organisms. In addition, risk for M.
      genitalium was higher for women with a black partner (adjusted odds ratio [AOR]:
      3.4; 95% confidence interval = 1.83-6.29), those never married (AOR: 2.6; 1.08
      6.25), using Depo-Provera (AOR: 2.3; 1.19-4.46), and smoking (AOR: 1.7; 1.03
      2.83). Drug use, history of STI in the past year, <=high school education,
      meeting and having intercourse the same day, anal sex, douching, and hormonal
      contraception were associated with N. gonorrhoeae or C. trachomatis, but not with
      M. genitalium. Number of partners was not associated with any of the 3 organisms.
      CONCLUSIONS: The limited number of risk factors for prevalent infection common to
      all 3 pathogens suggests that M. genitalium may circulate in different sexual
      networks than N. gonorrhoeae or C. trachomatis. The predominance of
      sociodemographic risk factors for M. genitalium, rather than high-risk sexual
      behaviors, suggests broad-based testing may be the most effective control
      strategy.

PMID- 20679964
TI  - Syphilis and methamphetamine use among female sex workers in Shandong Province,
      China.
AB  - A study of female sex workers in China, found alarmingly high prevalence of
      methamphetamine use. Methamphetamine users were more likely to be single,
      younger, inconsistent condom users, and have syphilis.

PMID- 20679965
TI  - Syphilis testing behavior following diagnosis with early syphilis among men who
      have sex with men--San Francisco, 2005-2008.
AB  - BACKGROUND: In San Francisco, men who have sex with men (MSM) with early syphilis
      are at high risk of reinfection. We described syphilis testing behavior among MSM
      after diagnosis, identified factors associated with not testing, and developed
      algorithms to identify nontesters. METHODS: We used syphilis surveillance data
      from 2005 through 2008 to describe follow-up testing behavior among MSM with
      early syphilis and titers of non-treponemal serologic tests >=1:16. We analyzed
      data from contact-tracing interviews to identify factors associated with not
      testing during the 1 to 6 months post-diagnosis. We developed and applied a
      multivariate model in a derivation set (2005-2006) and a validation set (2007
      2008), respectively, calculating correct classification rates (CCR) to assess
      predictive ability and evaluating patient characteristics for potential
      interventions. RESULTS: Among 795 MSM, 260 (33%) did not have a follow-up
      syphilis test. Not testing was associated with being HIV-uninfected (risk ratio
      [RR]: 1.9, 95% confidence interval [CI]: 1.5-2.6), residing outside of San
      Francisco's gay-identified neighborhood (RR: 1.7, 95% CI: 1.0-2.9), and being
      diagnosed at the municipal sexually transmitted disease clinic (RR: 1.5, 95% CI:
      1.2-2.0) (CCR derivation set, 71.6%; CCR validation set, 71.3%). An intervention
      focusing on MSM with those 3 characteristics would include 13% of syphilis cases
      among MSM and identify 26% of nontesters. CONCLUSIONS: Although MSM in San
      Francisco are at high risk for syphilis reinfection, one-third of MSM diagnosed
      with syphilis did not test during the 1 to 6 months post-diagnosis. Interventions
      to encourage follow-up testing among persons with syphilis might contribute to
      more effective syphilis prevention and control efforts.

PMID- 20679967
TI  - The politics of change.

PMID- 20679966
TI  - Severe hypernatremia in deceased liver donors does not impact early transplant
      outcome.
AB  - BACKGROUND: There may be an increased risk of primary nonfunction in livers
      procured from donors with hypernatremia. The purported mechanism for this effect
      is undefined. This study analyzes early graft function for donor livers procured
      from patients with severe hypernatremia. METHODS: The organ procurement records
      for 1013 consecutive deceased liver donors between 2001 and 2008 were reviewed.
      Both peak and terminal serum sodium levels were categorized as (1) severe for a
      level 170 mEq/L or higher, (2) moderate for 160 to 169 mEq/L, and (3) normal for
      less than 160 mEq/L. Outcomes included 30-day posttransplant alanine
      aminotransferase and total bilirubin, primary nonfunction, and 30-day and 1-year
      graft survival. RESULTS: Within the severe hypernatremia group, there were 142
      (peak) and 50 (terminal) donors, whereas the moderate group had 233 (peak) and
      162 (terminal) donors. The study groups did not differ in recipient age, model
      for end-stage liver disease score, steatosis, and ischemia times for the peak or
      terminal serum sodium groups. The differing levels of hypernatremia severity did
      not differ importantly, for peak or terminal serum sodium, in posttransplant
      alanine aminotransferase or total bilirubin, or the risk of intraoperative death
      and primary nonfunction. Thirty-day and 1-year graft survival did not demonstrate
      a negative impact from donor hypernatremia. CONCLUSIONS: Posttransplant measures
      of early liver function and risk of failure, up to 1-year posttransplant, did not
      differ significantly based on peak or terminal donor serum sodium levels. These
      results suggest that donor serum sodium level likely has little clinical impact
      on posttransplant liver function.

PMID- 20679968
TI  - Can self-care become an integrated part of end-of-life care? Implications for
      palliative nursing.

PMID- 20679969
TI  - A baseline review of medication provided to older people in nursing care homes in
      the last month of life.
AB  - AIM: Increasing numbers of older people are dying in the nursing care home
      setting. Little is known about the medication needs of the very old and frail in
      the last weeks of life and how they might differ from a model of care developed
      for people dying from cancer. METHOD: A baseline review of medication in the last
      month of life was undertaken to try and establish current practice of prescribing
      for this population. The notes of 48 deceased residents in seven nursing care
      homes were examined, alongside a questionnaire sent to 67 trained nurses.
      RESULTS: Subcutaneous prescribing only occurred where specialist palliative care
      teams had been involved with the residents' care. Syringe drivers were used in
      23% of cases; however, only three residents required a syringe driver for more
      than a day and a half. Nurses' confidence and competence in setting up syringe
      drivers was varied. CONCLUSIONS: The use of syringe drivers may not be the most
      appropriate way of managing symptoms during the dying phase in very frail and old
      people.

PMID- 20679970
TI  - Community nurses' experiences of ethical dilemmas in palliative care: a Swedish
      study.
AB  - AIM: The aim of this study was to highlight community nurses' experiences of
      ethical dilemmas in palliative care. BACKGROUND: There are many studies on
      palliative care but research on how community nurses experience ethical dilemmas
      in palliative home care is lacking. The ethical dilemmas to which these nurses
      are exposed seriously challenge their ethical competence. METHOD: Seven community
      nurses described their experiences of ethical dilemmas in palliative home care.
      The data was analysed by means of qualitative content analysis. FINDINGS: The
      core themes that emerged were: powerlessness, frustration, and concern in
      relation to ethical dilemmas in palliative care. The nurses were motivated and
      felt responsibility for their patients' end of life, and their relatives, and
      took their duties seriously. They wanted to satisfy all parties; the patient, the
      relatives and other palliative care professionals. CONCLUSION: The study confirms
      the need for knowledge about how community nurses experience dilemmas in ethical
      decision-making. They have the freedom to act and the willingness to make
      decisions, but they lack competence and knowledge about how their colleagues'
      experience and deal with such issues.

PMID- 20679971
TI  - How much compassion have I left? An exploration of occupational stress among
      children's palliative care nurses.
AB  - Nursing is a stressful occupation. While children's palliative care nurses
      encounter many of the stressors in common with other nurses, this unique context
      of care generates specific aspects of stress that warrant further examination.
      This qualitative study explores the experiences of stress in nurses providing
      children's palliative care in one region of the UK. In total, four focus groups
      took place with children's hospice nurses, community children's nurses and
      children's nurse specialists based in the regional children's hospital. The focus
      groups were taped, transcribed and analysed through the application of Newell and
      Burnard's thematic content analysis methodology. Four core themes emerged: work
      demands; relationships, maintaining control, and support and roles. Of particular
      note were stressors associated with the sub-themes of relationships, emotional
      demands and ethical conflicts. Conclusions illustrating how individuals and
      organizations may reduce the impact of stress in nurses contributing to the
      palliative care of children and their families are made.

PMID- 20679972
TI  - Thai Buddhist intensive care unit nurses' perspective of a peaceful death: an
      empirical study.
AB  - AIM: To describe the concept of a peaceful death from Thai Buddhist intensive
      care unit (ICU) nurses' perspectives. METHOD: A descriptive qualitative study of
      data generated from individual in-depth interviews of ten intensive care nurses
      who practiced in adult ICUs in the southern region of Thailand. Content analysis
      was used to analyse the data. FINDINGS: Four core qualities of a peaceful death
      emerged as described by Thai Buddhist nurses who practised in the ICUs. These
      core qualities are: peaceful mind; no suffering; family's acceptance of patient's
      death; and being with others and not alone. CONCLUSION: Thai Buddhist nurses
      described a peaceful death as 'a situation in which persons who are dying have
      peace of mind, and do not show signs and symptoms of suffering. Peaceful death
      occurs when family members declare acceptance of their loved one's dying and
      eventual death. Such a death is witnessed by relatives and friends and the dying
      person is not alone.' The findings encourage nurses to be with, and provide
      palliative care for, dying patients and families.

PMID- 20679973
TI  - Managing patients receiving sorafenib for advanced hepatocellular carcinoma: a
      case study.
AB  - Despite improvements in cytotoxic chemotherapy agents over the last 50 years, the
      outlook for patients with many of the most common solid tumours has remained
      poor. However, in recent years a number of targeted therapies have been licensed
      in the European Union for use in these cancer types. One such therapy, a tyrosine
      kinase inhibitor (sorafenib) is now used to treat patients with advanced
      hepatocellular carcinoma (HCC) and metastatic renal cell carcinoma. This article
      will explore the role of the oncology nurse in managing patients receiving
      sorafenib for advanced HCC. A brief overview of sorafenib as a current treatment
      approved for advanced HCC in the palliative setting is presented. This is
      followed by a case study-based discussion with particular reference to some of
      the key care coordination challenges facing the oncology nurse. The management of
      treatment-related adverse events and the importance of using a multidisciplinary
      team approach is also reviewed.

PMID- 20679974
TI  - Thinking about the effects of a natural disaster on existing palliative needs.

PMID- 20679977
TI  - Tackling undernutrition in older people from a regional perspective.
AB  - The aim of this article is to outline the issues of malnutrition in older people
      and national initiatives to effectively identify and treat undernutrition,
      concluding with a local example of how County Durham and Darlington is tackling
      undernutrition from a regional perspective through a service called Focus on
      Undernutrition.

PMID- 20679978
TI  - Day case gastrostomy placement for patients in the community.
AB  - The numbers of patients receiving home enteral feeding via a gastrostomy is
      increasing, with placement of the gastrostomy often being undertaken as a
      hospital day case. There are a number of benefits to the patient having the
      procedure in this way, however, problems may arise if a comprehensive assessment
      is not undertaken prior to the procedure, there is a lack of communication
      between hospital and community services, or inappropriate or inadequate training.
      It is essential to ensure that the transfer of care from acute hospital to
      community services is thorough to minimize these potential problems. This article
      aims to address some of the pitfalls that may occur when patients who require
      home enteral feeding are admitted to hospital for the placement of a gastrostomy
      and discharged from hospital into their own homes or into a care home the same
      day. Discussion will centre around the timing and assessment for gastrostomy
      placement, managing the risk of refeeding syndrome, devising a suitable feed
      regime, obtaining prescriptions, setting up community services and monitoring the
      patient's progress.

PMID- 20679979
TI  - Oral Aloe vera as a treatment for osteoarthritis: a summary.
AB  - While pain relief is a basic tenet of health care, pain is under-treated in the
      UK (Davies and Mcvicar, 2000) and this issue remains unresolved. This paper
      suggests that oral Aloe vera could be used in the treatment of chronic non-cancer
      pain (CNCP), particularly that caused by osteoarthritis (OA). Despite being used
      as arthritis treatment for centuries (Yoo et al, 2008), evidence of effectiveness
      of Aloe vera is anecdotal or from small studies. The perceived benefits of
      prescribing Aloe vera for OA may be twofold: it has utility as an anti
      inflammatory agent and also as a prophylactic against the gastrointestinal
      irritant effects of non-steroidal anti-inflammatory drugs (NSAIDs). Long-term,
      randomized, controlled studies are still needed to address the lack of evidence
      informing optimum prescribing of pain medication for people with OA (Cowan,
      2007). There is no reason that so called 'nutraceutical' agents should not be
      subjected to the same rigorous randomized, controlled, double-blind trials as
      other 'mainstream' drugs. Therefore, it is appropriate to ask whether NSAID
      treatment and side effects can be improved by the addition of oral Aloe vera.
      Thus, we may then be in a more informed position to resolve the ongoing
      'Pandemonium over Painkillers' (Cowan, 2007).

PMID- 20679980
TI  - Flexible working requests and the law: a guide for district nurses.
AB  - Flexible working provides employees with the ability to make it easier to balance
      work and caring responsibilities. All qualifying employees, including those who
      are district nurses, have a right to request an adjustment to their working hours
      and work patterns. Where the request is refused an appeal can be made to an
      employment tribunal and further action can be considered on the grounds of
      discrimination.

PMID- 20679981
TI  - Developing the community environmental health role of the nurse.
AB  - This paper is a report from one phase of an exploratory case study. It
      investigated the environmental health concerns of members of communities within
      one city in the North East of Scotland. Individual interviews with stakeholders
      (n=21) and four focus groups were conducted with a convenience sample of
      community nurses (n=19). Community nurse participants believed that their
      environmental health role remains underdeveloped. They indicated that they do not
      view the NHS as a resource for environmental health information. An environmental
      role is constrained by the NHS not being perceived as a source of information or
      expert in environmental health. They described limited contact between community
      nurses and public health medicine and uncertainty and conflict of interest
      between clinical groups regarding the scope of an environmental health role.
      Policy makers could support the development of an environmental advocacy role--a
      pilot of this is required.

PMID- 20679982
TI  - Community nursing in an uncertain future.

PMID- 20679983
TI  - NHS staff: nurture is key.

PMID- 20679993
TI  - The contributions of Aschheim and Zondek to endocrinology.

PMID- 20679994
TI  - Deficiency of the insulin-like growth factor-binding protein acid-labile subunit
      (ALS) of the circulating ternary complex in children with short stature.
AB  - The acid-labile subunit (ALS) protein is a key component of the circulating 150
      kDa IGF ternary complex. The main role of ALS is the extension of IGF-I half life
      by protecting it from degradation and preventing the passage of IGF-I to the
      extravascular compartment. In humans, complete ALS deficiency is characterized by
      severe reduction of IGF-I and IGFBP-3 that remain low after GH treatment,
      associated with mild growth retardation, much less pronounced than the IGF-I
      deficit. Pubertal delay in boys and insulin insensitivity are common findings. At
      least 21 patients with ALS deficiency have been described presenting 16 different
      homozygous or compound heterozygous inactivating mutations of the IGFALS gene.
      Although the effect of ALS deficiency on prenatal growth is still uncertain,
      postnatal growth is clearly affected, with the majority of the patients
      presenting a height between -2 to -3 SDS before and during puberty. In the
      assessment of a child with short stature ALS deficiency should be considered in
      those patients presenting: 1) a normal response to GH stimulation test, 2) low
      IGF-I levels associated with more profoundly reduced IGFBP-3 levels, 3) a mild
      growth retardation, apparently out of proportion to the degree of IGF-I and IGFBP
      3 deficits, 4) lack of response to an IGF generation test and 5) insulin
      insensitivity. The relatively mild growth retardation in relation to the severe
      IGF-I deficit might be related to the preserved autocrine/paracrine action of
      locally produced IGF-I. The observation that in families of ALS deficient
      patients, heterozygous carriers for IGFALS gene mutations are shorter than their
      wild type relatives and the relatively high frequency of heterozygosity for this
      gene in children with idiopathic short stature suggests a requirement of normal
      levels of ALS for the attainment of maximal growth potential.

PMID- 20679996
TI  - Longevity of the hypopituitary patients from the island Krk: a follow-up study.
AB  - Patients with dwarfism on the Krk island in the Adriatic Sea have been known
      since 1864. Since then 25 related dwarfs (15 males and 10 females) originating
      from the villages Bascanska Draga and Jurandvor have been recorded. The last
      patient was born in 1996 and was diagnosed in 2004. In 1988 we were able to prove
      that the etiology of the hereditary multiple pituitary deficiencies (MPHD)
      causing the dwarfism is due to a PROP-1 gene mutation, a pituitary transcription
      factor. During visits in 1988, 1990 and 2007 data on the life span of these
      patients not treated by growth and sex hormone were collected. We found data for
      9 patients (5 males and 4 females). One female died in an accident at age 61; 6
      patients (3 males and 3 females) died between ages 68 and 91 due to
      cardiovascular disease. Two males died at ages 77 and 83, cause unknown. It is
      concluded that despite the long lasting GH and sex hormone deficiencies and
      irregular thyroid hormone ingestion, patients with congenital MPHD due to Prop-1
      gene defects can live a long life.

PMID- 20679995
TI  - Pathophysiology, assessment and management of the child with growth hormone
      resistance.
AB  - Defects in the growth hormone (GH)-insulin-like growth factor (IGF)I axis may
      cause GH resistance characterized by IGFI deficiency and growth failure. The
      range of defects causing GH resistance is broad as are their biochemical and
      phenotypical characteristics. We propose that GH-IGFI axis defects form a
      continuum of clinical and biochemical effects ranging from GH deficiency to GH
      resistance. The pathophysiology of GH resistance is described followed by a
      scheme for investigation of the child with severe short stature and normal GH
      secretion. We critically discuss GH therapy for such patients and define
      acceptable growth responsiveness. Finally we discuss therapy with IGF-I within
      the limits of the USA Food and Drug Administration and European Medicines Agency
      labels for GH resistance.

PMID- 20679997
TI  - Severe hypercalcemia in a patient treated for hypoparathyroidism with calcitriol.
AB  - Long term administration of calcitriol (1,25 - dihydroxyvitamin D) is recommended
      for the treatment of a number of endocrine and renal disorders associated with
      impaired calcium - phosphate metabolism. Administration of calcitriol, however,
      may give rise to undesirable side effects, such as hypercalcemia and
      hypercalciuria. The magnitude of hypercalcemia is the key consideration in
      determining the need for immediate and aggressive therapy. There are four main
      strategies for lowering serum calcium: decreasing intestinal calcium absorption;
      increasing urinary excretion; decreasing bone resorption; and removing excess
      calcium through dialysis. We report on an adolescent with thalassemia who
      developed severe hypercalcemia during regular clinical follow-up for
      hypoparathyroidism treatment with calcitriol and calcium. He was also receiving
      levothyroxine for primary hypothyroidism and iron chelation therapy with
      desferioxamine mesylate for the severe iron overload.

PMID- 20679999
TI  - Conference calendar: is less more?

PMID- 20679998
TI  - Mosaic zebrafish transgenesis for evaluating enhancer sequences.
AB  - The completion of the human genome sequence, along with that of many other
      species, has highlighted the challenge of ascribing specific function to non
      coding sequences. One prominent function carried out by the non coding fraction
      of the genome is to regulate gene transcription; however, there are no effective
      methods to broadly predict cis-regulatory elements from primary DNA sequence. We
      have developed an efficient protocol to functionally evaluate potential cis
      regulatory elements through zebrafish transgenesis. Our approach offers
      significant advantages over cell-culture based techniques for developmentally
      important genes, since it provides information on spatial and temporal gene
      regulation. Conversely, it is faster and less expensive than similar experiments
      in transgenic mice, and we routinely apply it to sequences isolated from the
      human genome. Here we demonstrate our approach to selecting elements for testing
      based on sequence conservation and our protocol for cloning sequences and
      microinjecting them into zebrafish embryos.

PMID- 20680000
TI  - Knowing when to change: reprogramming (my) life.

PMID- 20680001
TI  - A metabolic assembly line in bacteria.

PMID- 20680002
TI  - The plasma membrane brings autophagosomes to life.

PMID- 20680007
TI  - Conditional ablation of glycogen synthase kinase 3beta in postnatal mouse kidney.
AB  - Glycogen synthase kinase (GSK)3 is a ubiquitously expressed serine/threonine
      kinase existing in two isoforms, namely GSK3alpha and GSK3beta. Aside from the
      long-recognized role in insulin signal transduction and glycogen biosynthesis,
      GSK3beta has been recently coined as a master control molecule in nuclear factor
      kappaB activation and inflammatory kidney injury. Nevertheless, previous studies
      are less conclusive because they relied greatly on small molecule inhibitors,
      which lack selectivity and barely distinguish between the GSK3 isoforms. In
      addition, early embryonic lethality after global knockout of GSK3beta precludes
      interrogation of the biological role of GSK3beta in the adult kidney. To
      circumvent these issues, the Cre/loxP system was used to generate a conditional
      knockout mouse model in which the GSK3beta gene was specifically deleted in
      kidney cortical tubules at postnatal mature stage. Kidney-specific ablation of
      GSK3beta resulted in a phenotype no different from control littermates. Knockout
      mice (KO) were viable and exhibited normal development and normal kidney
      physiology in terms of kidney function, urine albumin excretion, and urine
      concentrating ability. It is noteworthy that apart from normal glomerular and
      tubulointerstitial morphology, the kidneys from KO demonstrated more glycogen
      accumulation in the renal cortical tubules as assessed by both periodic acid
      Schiff staining for light microscopy and direct biochemical assay, consistent
      with an elevated glycogen synthetic activity as evidenced by diminished
      inhibitory phosphorylation of glycogen synthase that occurred subsequent to
      GSK3beta ablation. This finding was further validated by electron microscopic
      observations of increased deposition of glycogen particles in the renal tubules
      of KO, suggesting that GSK3alpha could not fully compensate for the loss of
      GSK3beta in regulating glycogen metabolism in the kidney. Collectively, our study
      suggests that kidney-specific ablation of GSK3beta barely affects kidney function
      and histology under normal circumstances. Extended examinations of these KO under
      diseased conditions are merited to understand the role of GSK3beta in renal
      pathophysiology.

PMID- 20680008
TI  - Induction of liver fibrosis in a murine hepatoma model by thioacetamide is
      associated with enhanced tumor growth and suppressed antitumor immunity.
AB  - Liver cirrhosis and hepatocellular carcinomas are two major causes of morbidity
      and mortality worldwide, and can synergistically interact to expedite the tumor
      progression. How fibrosis promotes the hepatoma growth remains completely
      unexplained. Using an in situ murine hepatoma model together with fibrosis
      induction by thioacetamide (TAA), the hepatoma growth and the immune factors in
      the fibrotic liver were analyzed. We found that TAA-fibrosis induction enhanced
      hepatoma cell growth in the liver and increased the mortality of hepatoma-bearing
      mice. The tumor-infiltrating CD4(+) or CD8(+) T cells are downregulated by
      fibrosis induction. The Foxp3(+) regulatory T cells (Treg) cells were induced. We
      conclude that fibrosis induction causes further immunosuppression, in which Treg
      cells exert a downregulation effect on the antitumor immunity.

PMID- 20680009
TI  - Fibroblasts stimulated via HLA-II molecules produce prostaglandin E2 and regulate
      cytokine production from helper T cells.
AB  - Fibroblasts act as important immune regulatory cells via their ability to cross
      talk with T cells accumulating in lesions. Our previous study showed that
      fibroblasts produce several cytokines and chemokines by crosslinking HLA class II
      (HLA-II) molecules with monoclonal antibodies or by making T-cell receptor
      peptide-HLA complexes. It is thus conceivable that the interaction of T cells and
      fibroblasts via HLA-II affects fibroblast responses to stimuli. This study used
      human gingival fibroblasts (HGF) to investigate possible effects of these
      fibroblast-derived soluble factors on the differentiation of naive T cells and on
      the subsequent fibroblast responses. After mixed lymphocyte reaction culture
      between naive T cells and allogeneic dendritic cells in the presence of culture
      supernatant from HGF stimulated via HLA-DQ molecules (DQ-sup), but not via DR, T
      cells exhibited a Th2-shifted phenotype, thereby producing quantitatively more IL
      13 and IL-5 compared with interferon-gamma. Astonishingly, analyses to identify
      possible factors affecting the Th2 polarization secreted from HLA-II-stimulated
      HGF, prostaglandin E2, was detected only in DQ-sup. The Th2 polarization of naive
      T cells was blocked in the presence of supernatants from indomethacin-treated HGF
      with HLA-DQ stimulation. In addition, we found that the culture supernatants of
      Th cells activated following mixed lymphocyte reaction culture in the presence of
      DQ-sup had the potential to induce gene expression of type I and III collagens in
      HGF. These results suggested that fibroblasts stimulated via HLA-DQ molecules
      promote Th2 polarization in Th-cell responses and showed the counter activation
      of collagen synthesis, implicating orchestrated responses among these cells in
      the fibrosis of chronic inflammatory lesions.

PMID- 20680010
TI  - Hindbrain interneurons and axon guidance signaling critical for breathing.
AB  - Breathing is a bilaterally synchronous behavior that relies on a respiratory
      rhythm generator located in the brainstem. An essential component of this
      generator is the preBotzinger complex (preBotC), which paces inspirations. Little
      is known about the developmental origin of the interneuronal populations forming
      the preBotC oscillator network. We found that the homeobox gene Dbx1 controls the
      fate of glutamatergic interneurons required for preBotC rhythm generation in the
      mouse embryo. We also found that a conditional inactivation in Dbx1-derived cells
      of the roundabout homolog 3 (Robo3) gene, which is necessary for axonal midline
      crossing, resulted in left-right de-synchronization of the preBotC oscillator.
      Together, these findings identify Dbx1-derived interneurons as the core
      rhythmogenic elements of the preBotC oscillator and indicate that Robo3-dependent
      guidance signaling in these cells is required for bilaterally synchronous
      activity.

PMID- 20680011
TI  - The relationship between overweight and otitis media with effusion in children.
AB  - OBJECTIVE: To assess the relationship between pediatric otitis media with
      effusion (OME) and body mass index (BMI). METHODS: We assessed 140 children aged
      2-7 years who underwent unilateral or bilateral ventilation tube insertion for
      treatment of OME (experimental group) and 190 children with no history of OME who
      underwent operations for conditions other than ear diseases during the same
      period. Each group was divided into four subgroups based on BMI by age and
      gender: underweight (BMI below normal limits; BMI <= 5 th percentile), normal
      (BMI within normal limits; 5th < BMI < 85th percentile), overweight (BMI over
      normal limits; 85 th <= BMI < 95th percentile) and obese ( BMI >= 95 th
      percentile). We explored differences in BMI, and serum triglycerides (TG) and
      total cholesterol (TC), between the experimental and control group, in comparison
      with values from those of standard body weight. RESULTS: The prevalence of
      obesity was significantly higher in the experimental than in the control group
      (P<0.05). BMI, TG and TC did not, however, differ significantly between groups,
      according to standard body weight. CONCLUSION: Pediatric obesity may have an
      effect on the development of OME, but pediatric overweight may be not associated
      with occurrence of OME.

PMID- 20680013
TI  - Reply to B Wansink and CS Wansink.

PMID- 20680012
TI  - A motivation-focused weight loss maintenance program is an effective alternative
      to a skill-based approach.
AB  - OBJECTIVE: Maintaining weight loss is a major challenge in obesity treatment.
      Individuals often indicate that waning motivation prompts cessation of effective
      weight management behaviors. Therefore, a novel weight loss maintenance program
      that specifically targets motivational factors was evaluated. DESIGN: Overweight
      women (N=338; 19% African American) with urinary incontinence were randomized to
      lifestyle obesity treatment or control and followed for 18 months. All
      participants in lifestyle (N=226) received the same initial 6-month group
      behavioral obesity treatment and were then randomized to (1) a novel motivation
      focused maintenance program (N=113) or (2) a standard skill-based maintenance
      approach (N=113). MAIN OUTCOME MEASURE: Weight assessed at baseline, 6 and 18
      months. RESULTS: Both treatment groups (motivation-focused and skill-based)
      achieved comparable 18-month weight losses (-5.48% for motivation-focused vs 
      5.55% in skill-based, P=0.98), and both groups lost significantly more than
      controls (-1.51%; P=0.0012 in motivation-focused and P=0.0021 in skill-based).
      CONCLUSIONS: A motivation-focused maintenance program offers an alternative,
      effective approach to weight maintenance expanding available evidence-based
      interventions beyond traditional skill-based programs.

PMID- 20680014
TI  - Asian Americans have greater prevalence of metabolic syndrome despite lower body
      mass index.
AB  - OBJECTIVE: To examine the relationship between body mass index (BMI) and
      metabolic syndrome for Asian Americans and non-Hispanic Whites (NHWs), given that
      existing evidence shows racial/ethnic heterogeneity exists in how BMI predicts
      metabolic syndrome. RESEARCH DESIGN AND METHODS: Electronic health records of
      43,507 primary care patients aged 35 years and older with self-identified
      race/ethnicity of interest (Asian Indian, Chinese, Filipino, Japanese, Korean,
      Vietnamese or NHW) were analyzed in a mixed-payer, outpatient-focused health-care
      organization in the San Francisco Bay Area. RESULTS: Metabolic syndrome
      prevalence is significantly higher in Asians compared with NHWs for every BMI
      category. For women at the mean age of 55 and BMI of 25  kg  m(-2), the predicted
      prevalence of metabolic syndrome is 12% for NHW women compared with 30% for
      Asians; similarly for men, the predicted prevalence of metabolic syndrome is 22%
      for NHWs compared with 43% of Asians. Compared with NHW women and men with a BMI
      of 25  kg  m(-2), comparable prevalence of metabolic syndrome was observed at BMI
      of 19.6  kg  m(-2) for Asian women and 19.9  kg  m(-2) for Asian men. A similar
      pattern was observed in disaggregated Asian subgroups. CONCLUSIONS: In spite of
      the lower BMI values and lower prevalence of overweight/obesity than NHWs, Asian
      Americans have higher rates of metabolic syndrome over the range of BMI. Our
      results indicate that BMI ranges for defining overweight/obesity in Asian
      populations should be lower than for NHWs.

PMID- 20680016
TI  - A systematic review on animal models of maternal high fat feeding and offspring
      glycaemic control.
AB  - The mechanistic link between obese parents and obese offspring and the relative
      role of genes, and a shared environment is not completely understood. Animal
      models help us to differentiate between genetic and environmental factors, and
      the interaction between the two. However, the willingness of researchers to blend
      results from multiple models makes it difficult for clear mechanisms to be
      identified for specific hypothesis-driven research. As such we conducted a
      systematic review of animal models of maternal high fat feeding in an effort to
      identify the affect on the offspring glycaemic control. Maternal and offspring
      outcomes are reported in an effort to identify possible relationships to
      facilitate and focus on future research. We present here data from 11 studies
      investigating glycaemic control in offspring exposed to a high fat diet (HFD)
      during maternal gestation only or gestation and lactation. Studies in this review
      identify a real risk of type 2 diabetes and obesity in male offspring exposed to
      a maternal HFD. Poor glycaemic control in the offspring appears to be independent
      of maternal obesity, birth weight or post-weaning macronutrient intake.
      Inconsistencies between studies however, limit our capacity to identify
      mechanisms for the developmental origin of these diseases in animal models of
      overnutrition.

PMID- 20680015
TI  - Use of self-reported height and weight biases the body mass index-mortality
      association.
AB  - BACKGROUND: Many large-scale epidemiological data sources used to evaluate the
      body mass index (BMI: kg/m(2)) mortality association have relied on BMI derived
      from self-reported height and weight. Although measured BMI (BMI(M)) and self
      reported BMI (BMI(SR)) correlate highly, self-reports are systematically biased.
      OBJECTIVE: To rigorously examine how self-reporting bias influences the
      association between BMI and mortality rate. SUBJECTS: Samples representing the US
      non-institutionalized civilian population. DESIGN AND METHODS: National Health
      and Nutrition Examination Survey data (NHANES II: 1976-80; NHANES III: 1988-94)
      contain BMI(M) and BMI(SR). We applied Cox regression to estimate mortality
      hazard ratios (HRs) for BMI(M) and BMI(SR) categories, respectively, and compared
      results. We similarly analyzed subgroups of ostensibly healthy never-smokers.
      RESULTS: Misclassification by BMI(SR) among the underweight and obesity ranged
      from 30-40% despite high correlations between BMI(M) and BMI(SR) (r>0.9). The
      reporting bias was moderately correlated with BMI(M) (r>0.35), but not BMI(SR)
      (r<0.15). Analyses using BMI(SR) failed to detect six of eight significant
      mortality HRs detected by BMI(M). Significantly biased HRs were detected in the
      NHANES II full data set (chi(2)=12.49; P=0.01) and healthy subgroup (chi(2)=9.93;
      P=0.04), but not in the NHANES III full data set (chi(2)=5.63; P=0.23) or healthy
      subgroup (chi(2)=1.52; P=0.82). CONCLUSIONS: BMI(SR) should not be treated as
      interchangeable with BMI(M) in BMI mortality analyses. Bias and inconsistency
      introduced by using BMI(SR) in place of BMI(M) in BMI mortality estimation and
      hypothesis tests may account for important discrepancies in published findings.

PMID- 20680017
TI  - Effects of acute dietary restriction on gut motor, hormone and energy intake
      responses to duodenal fat in obese men.
AB  - BACKGROUND: Previous patterns of energy intake influence gastrointestinal
      function and appetite, probably reflecting changes in small-intestinal nutrient
      mediated feedback. Obese individuals consume more fat and may be less sensitive
      to its gastrointestinal and appetite-suppressant effects than lean individuals.
      OBJECTIVE: To evaluate the hypothesis that, in obese individuals, the effects of
      duodenal fat on gastrointestinal motor and hormone function, and appetite would
      be enhanced by a short period on a very-low-calorie diet (VLCD). METHODS: Eight
      obese men (body mass index 34+/-0.6  kg  m(-2)) were studied on two occasions,
      before (V1), and immediately after (V2), a 4-day VLCD. On both occasions,
      antropyloroduodenal motility, plasma cholecystokinin (CCK), peptide-YY (PYY) and
      ghrelin concentrations, and appetite perceptions were measured during a 120-min
      intraduodenal fat infusion (2.86  kcal  min(-1)). Immediately afterwards, energy
      intake was quantified. RESULTS: During V2, basal pyloric pressure and the number
      and amplitude of isolated pyloric pressure waves (PWs) were greater, whereas the
      number of antral and duodenal PWs was less, compared with V1 (all P<0.05).
      Moreover, during V2, baseline ghrelin concentration was higher; the stimulation
      of PYY and suppression of ghrelin by lipid were greater, with no difference in
      CCK concentration; and hunger and energy intake (kJ; V1: 4378+/-691, V2: 3634+/
      700) were less (all P<0.05), compared with V1. CONCLUSIONS: In obese males, the
      effects of small-intestinal lipid on gastrointestinal motility and some hormone
      responses and appetite are enhanced after a 4-day VLCD.

PMID- 20680018
TI  - Taste, olfactory and food texture reward processing in the brain and obesity.
AB  - Complementary neuronal recordings and functional neuroimaging in humans, show
      that the primary taste cortex in the anterior insula provides separate and
      combined representations of the taste, temperature and texture (including fat
      texture) of food in the mouth independently of hunger and thus of reward value
      and pleasantness. One synapse on, in the orbitofrontal cortex (OFC), these
      sensory inputs are for some neurons combined by learning with olfactory and
      visual inputs, and these neurons encode food reward in that they only respond to
      food when hungry, and in that activations correlate with subjective pleasantness.
      Cognitive factors, including word-level descriptions, and attention, modulate the
      representation of the reward value of food in the OFC. Further, there are
      individual differences in the representation of the reward value of food in the
      OFC. It is argued that overeating and obesity are related in many cases to an
      increased reward value of the sensory inputs produced by foods, and their
      modulation by cognition and attention, which overrides existing satiety signals.
      It is proposed that control of all rather than one or several of these factors
      that influence food reward and eating may be important in the prevention and
      treatment of overeating and obesity.

PMID- 20680019
TI  - Development of the eating behaviour in Prader-Willi Syndrome: advances in our
      understanding.
AB  - Prader-Willi Syndrome (PWS) is a genetically determined neurodevelopmental
      disorder associated with mild to moderate intellectual disability, growth and sex
      hormone deficiencies and a propensity to overeat that leads to severe obesity.
      The PWS phenotype changes from an early disinterest in food to an increasing pre
      occupation with eating and a failure of the normal satiety response to food
      intake. The prevention of severe obesity is primarily through strict control of
      access to food and it is this aspect that most limits the independence of those
      with PWS. This review considers the eating disorder in PWS, specifically how the
      as yet uncertain genetics of the syndrome and the transition from the early to
      the later phenotype might account for the later hyperphagia. On the basis of
      behavioural and imaging studies, a failure of satiety and excessive activation of
      neural reward pathways have both been suggested. We speculate that the overeating
      behaviour, consequent upon one or other of the above, could either be due to a
      direct effect of the PWS genotype on the feeding pathways of the hypothalamus or
      a consequence of prenatal changes in the regulation of genes responsible for
      energy balance that sets a high satiation threshold. Understanding the overeating
      in PWS will lead to more focused and successful management and ultimately,
      treatment of this life-threatening behaviour.

PMID- 20680020
TI  - The choice of assisted ejaculation method is relevant for the diagnosis of
      azoospermia in men with spinal cord injuries.
AB  - STUDY DESIGN: Retrospective analysis of research data collected over >18 years at
      our center. OBJECTIVES: Examine results of repeated semen retrievals in men with
      spinal cord injury (SCI) who were initially found to be azoospermic. SETTING:
      Major university medical center. METHODS: Three different groups were analyzed in
      this study. Group 1 (n = 15) consisted of patients who were found to be
      azoospermic after the first ejaculation obtained by penile vibratory stimulation
      (PVS) and who had subsequent ejaculates obtained by PVS. Group 2 (n = 8)
      consisted of patients who were found to be azoospermic after the first
      ejaculation obtained by PVS and who had subsequent ejaculates obtained by
      electroejaculation (EEJ). Group 3 (n = 18) consisted of patients who were found
      to be azoospermic after the first ejaculation obtained by EEJ and who had
      subsequent ejaculates obtained by EEJ. RESULTS: In group 1 (PVS-PVS), the second
      ejaculate contained sperm in none of the 15 patients. In group 2 (PVS-EEJ), the
      second ejaculate contained sperm in three of eight patients. In group 3 (EEJ
      EEJ), the second EEJ resulted in semen with sperm in 6 of 18 patients. In the 388
      study subjects, the overall prevalence of azoospermia was 7.0%. CONCLUSION: In a
      study of a large group of subjects with SCI, the vast majority had normal sperm
      concentrations. In the minority who were azoospermic on their first ejaculate,
      and who were past the acute phase of injury, obtaining a second ejaculate by EEJ
      versus PVS may be a reasonable step before proceeding to surgical sperm
      retrieval.

PMID- 20680021
TI  - The AuSpinal: a test of hand function for people with tetraplegia.
AB  - STUDY DESIGN: Five-phased reliability and validity study. OBJECTIVES: To develop
      and test an assessment tool designed to quantify unilateral hand function in
      people with tetraplegia. SETTING: Seven spinal injury units in Australia.
      METHODS: The AuSpinal is a new assessment tool comprising seven tasks designed to
      quantify unilateral hand function in people with tetraplegia. There were five
      phases in this study: (1) development of the AuSpinal; (2) testing the test
      retest and intrarater reliability of repeat ratings of 84 videos as determined by
      13 therapists; (3) testing the interrater reliability and internal consistency of
      simultaneous real-life ratings of eight hands as determined by six therapists;
      (4) testing the range of scores from cross-sectional data obtained from 50 hands;
      and (5) quantifying sensitivity to change from longitudinal data collected over
      the course of rehabilitation from 16 hands. RESULTS: The test-retest, intrarater
      and interrater reliabilities were high (intraclass correlation coefficients
      ranged from 0.79 to 0.98, 95% CI ranged from 0.72 to 1.0) with a Cronbach alpha
      value of 0.93. There was a reasonable range in the scores obtained from the cross
      sectional data of the 50 hands (interquartile range extended from 6 to 14). There
      was an obvious and marked change in AuSpinal scores over the course of patients'
      rehabilitation in 8 of the 16 hands. CONCLUSION: The AuSpinal provides a quick
      and reliable instrument to test hand function in people with tetraplegia. It is
      useful for people with poor hand function but requires the addition of more
      complex tasks for those with good hand function.

PMID- 20680022
TI  - Gene regulation: Small ORFs conceal bioactive peptides.

PMID- 20680023
TI  - DNA methylation: Looking beyond promoters.

PMID- 20680025
TI  - Prime-boost vaccinations using recombinant flavivirus replicon and vaccinia virus
      vaccines: an ELISPOT analysis.
AB  - Recombinant Kunjin replicon virus-like particle (VLP), vaccinia virus (rVV) and
      DNA vaccines were tested in a large series of prime-boost vaccinations using
      interferon (IFN)gamma ELISPOT assays that reflected effector (E), effector memory
      (EM) and central memory (CM) responses. All vaccine constructs encoded the murine
      polytope immunogen and responses to four CD8 T-cell epitopes (TYQRTRALV,
      SYIPSAEKI, YPHFMPTNL and RPQASGVYM) were measured. VLP/rVV out performed (by 14-
      to 20-fold) DNA/rVV for induction of CM responses, whereas EM responses were only
      marginally increased. DNA/VLP induced more EM, but not CM responses, than VLP
      alone, illustrating that DNA priming is not universally beneficial. rVV/VLP gave
      comparable results to VLP/rVV combinations, although the former induced
      approximately threefold more E responses, illustrating the utility of poxvirus
      priming in this setting. Although higher doses of VLP and rVV increased responses
      after single immunizations, such dose increases provided only marginal benefit in
      heterologous prime-boost settings. Triple combinations also provided no benefit
      over two vaccinations. DNA vaccination was associated with broad CM, but not EM
      responses, and the breadth of EM and E responses was significantly improved by
      increasing viral vector dose. VLP/rVV, rather than DNA priming, induced T cells
      with consistently high IFNgamma secretion profiles across all ELISPOT measures.
      Vector-specific CD8 T-cell responses generally correlated well with immunogen
      specific responses, although, as expected, single use of each vector reduced the
      relative levels of vector-specific responses. These experiments illustrate the
      utility of replicons in heterologous prime-boost vaccinations, and illustrate the
      diversity of data that can be obtained from ELISPOT analyses.

PMID- 20680026
TI  - Expression of chemokine decoy receptors and their ligands at the porcine maternal
      fetal interface.
AB  - Successful pregnancy requires coordinated maternal-fetal cross-talk to establish
      vascular connections that support conceptus growth. In pigs, two waves of
      spontaneous fetal loss occur and 30-40% of conceptuses are lost before
      parturition. Previous studies associated these losses with decreased angiogenic
      and increased inflammatory cytokines. Chemokines, a sub-category of cytokines,
      and decoy receptors control leukocyte trafficking, angiogenesis and development.
      The availability of chemokines is regulated by three non-signalling decoy
      receptors: chemokine decoy receptor (D6), Duffy antigen receptor for chemokines
      (DARC) and Chemocentryx decoy receptor (CCX CKR). We hypothesized that the
      expression of these receptors and their chemokine ligands regulate the porcine
      pregnancy success or failure. Here, we describe for the first time the
      transcription and translation of all three decoy receptors and several chemokine
      ligands in endometrium and trophoblast associated with healthy and arresting
      conceptuses at gestation day (gd) 20 and gd50. Among decoy receptors, transcripts
      for DARC were significantly reduced in endometrium, whereas that for CCX CKR were
      significantly increased in endometrium and trophoblast at gd50 arresting compared
      with healthy sites. However, western blot analysis revealed no differences in
      decoy receptor expression between healthy and arresting tissues. Transcripts for
      decoy receptor ligands CCL2, CCL3, CCL4, CCL5, CCL11, CCL19, CCL21, CXCL2 and
      CXCL8 were stable between healthy and arresting littermates. Quantification by
      SearchLight chemiluminescent protein array confirmed ligand expression at the
      protein level. These data indicate that decoy receptors and ligands are expressed
      at the porcine maternal-fetal interface and dysregulation of decoy receptor (DARC
      and CCX CKR) transcripts occurs at sites of fetal arrest.

PMID- 20680024
TI  - Measuring selection in contemporary human populations.
AB  - Are humans currently evolving? This question can be answered using data on
      lifetime reproductive success, multiple traits and genetic variation and
      covariation in those traits. Such data are available in existing long-term,
      multigeneration studies - both clinical and epidemiological - but they have not
      yet been widely used to address contemporary human evolution. Here we review
      methods to predict evolutionary change and attempts to measure selection and
      inheritance in humans. We also assemble examples of long-term studies in which
      additional measurements of evolution could be made. The evidence strongly
      suggests that we are evolving and that our nature is dynamic, not static.

PMID- 20680027
TI  - Differentiation of induced pluripotent stem cells to thymic epithelial cells by
      phenotype.
AB  - Thymic epithelial cells (TECs) are present in both cortical and medullary thymic
      areas, and have crucial roles in functional T-cell development. In this study, we
      studied the differentiation of induced pluripotent stem cells (iPSCs) to TEC.
      When iPSC were cultured for 4 days in collagen IV-coated dishes in the presence
      of both activin A and lithium chloride (LiCl), the cells differentiated to
      definitive endoderm through mesendoderm. Further treatment with Fgf8 followed by
      Fgf7, Fgf10 and BMP4 differentiated iPSC to thymic epithelial progenitor cells
      (TEPCs) by phenotype. Gene expression of Hoxa3, Pax1 and Pax9 was observed and
      cell surface proteins EpCAM1 and MTS24 were detected at day 14 of iPSC
      differentiation. TEPCs differentiated to medullary TECs (mTECs) by phenotype
      following the addition of receptor activator nuclear factor B ligand with LiCl.
      Thus, we successfully induced efficient differentiation from mouse iPSC to TEPCs
      and mTEC by phenotype using chemically defined conditions.

PMID- 20680028
TI  - Association between HTR2C gene polymorphisms and the metabolic syndrome in
      patients using antipsychotics: a replication study.
AB  - In two previous studies we found an association between HTR2C polymorphisms and
      the prevalence of the metabolic syndrome in patients using antipsychotics. In
      this study, we set out to replicate our findings in a third separate sample of
      patients. Data for this cross-sectional study came from the ongoing
      Pharmacotherapy Monitoring and Outcome survey study, investigating the
      association between schizophrenia and metabolic or cardiovascular risk factors.
      Primary end point was the prevalence of the metabolic syndrome. Primary
      determinants were two polymorphisms in the HTR2C gene: rs3813929 (-759 C/T) and
      rs1414334:C>G. Carriership of the variant rs1414334 C-allele was significantly
      associated with an increase prevalence of the metabolic syndrome (odds ratio (OR)
      3.73; 95% confidence interval (CI) 1.29-10.79, P=0.015). No association was found
      between the HTR2C -759 C/T polymorphism and the metabolic syndrome. This study
      confirms previous findings that the variant C-allele of the rs1414334
      polymorphism is associated with the metabolic syndrome.

PMID- 20680029
TI  - The implementation of screening for prostate cancer.
AB  - The objective of this study was to determine whether screening for prostate
      cancer (PC) reduces PC mortality and, if so, whether the required criteria to be
      introduced as a population-based screening program are satisfied. A literature
      review was conducted through electronic scientific databases. The screening
      tests, that is, PSA and digital rectal examination, have limited sensitivity and
      specificity for detecting PC; screening produces a beneficial stage shift and
      reduces PC mortality. Nevertheless, PC screening causes a large increase in the
      cumulative incidence, and the understanding of the economic cost and quality-of
      life parameters are limited. PC screening cannot be justified yet in the context
      of a public health policy.

PMID- 20680030
TI  - Curcumin interrupts the interaction between the androgen receptor and Wnt/beta
      catenin signaling pathway in LNCaP prostate cancer cells.
AB  - Recently, studies have investigated the significance of the Wnt/beta-catenin
      pathway in prostate cancer. The transcriptional activity of the androgen receptor
      (AR) is modulated by interaction with coregulators, one of which is beta-catenin.
      Curcumin, a dietary yellow pigment of Curcuma longa, has emerged as having a
      chemopreventive role. Although curcumin has been shown to inhibit AR expression,
      its molecular mechanism has not been fully elucidated. In this study, whether
      curcumin mediates the Wnt/beta-catenin signaling pathway with regard to AR/beta
      catenin interactions was studied. Curcumin was shown to induce significant
      inhibition of AR expression in a dose-dependent manner. Marked curcumin-induced
      suppression of beta-catenin was shown in the nuclear and cytoplasmic extracts as
      well as whole cell lysates. Further analysis revealed that phosphorylation of Akt
      and glycogen synthase kinase-3beta were attenuated, but phosphorylated beta
      catenin was increased after curcumin treatment. Finally, cyclin D1 and c-myc, the
      target gene of the beta-catenin/T-cell factor transcriptional complex, were also
      decreased. These findings suggest that curcumin modulates the Wnt/beta-catenin
      signaling pathway and might have a significant role in mediating inhibitory
      effects on LNCaP prostate cancer cells.

PMID- 20680031
TI  - Effect of androgen deprivation therapy on the expression of prostate cancer
      biomarkers MSMB and MSMB-binding protein CRISP3.
AB  - We have investigated the effects of short-term neoadjuvant and long-term androgen
      deprivation therapies (ADTs) on beta-microseminoprotein (MSMB) and cysteine-rich
      secretory protein-3 (CRISP3) expression in prostate cancer patients. We also
      studied if MSMB expression was related to genotype and epigenetic silencing.
      Using an Affymetrix cDNA microarray analysis, we investigated the expression of
      MSMB, CRISP3, androgen receptor (AR), KLK3 and Enhancer of Zeste Homologue-2
      (EZH2) in tissue from prostate cancer patients receiving (n=17) or not receiving
      (n=23) ADT before radical prostatectomy. MSMB, CRISP3 and AR were studied in
      tissue from the same patients undergoing TURP before and during ADT (n=16). MSMB
      genotyping of these patients was performed by TaqMan PCR. MSMB and KLK3
      expression levels decreased during ADT. Expression levels of AR and CRISP3 were
      not affected by short-term ADT but were high in castration-resistant prostate
      cancer (CRPC) and metastases. Levels of EZH2 were also high in metastases, where
      MSMB was low. Genotyping of the MSMB rs10993994 polymorphism showed that the TT
      genotype conveys poor MSMB expression. MSMB expression is influenced by
      androgens, but also by genotype and epigenetic silencing. AR and CRISP3
      expression are not influenced by short-term ADT, and high levels were found in
      CRPC and metastases.

PMID- 20680032
TI  - Role of H3K27 methylation in the regulation of lncRNA expression.
AB  - Once thought to be transcriptional noise, large non-coding RNAs (lncRNAs) have
      recently been demonstrated to be functional molecules. The cell-type-specific
      expression patterns of lncRNAs suggest that their transcription may be regulated
      epigenetically. Using a custom-designed microarray, here we examine the
      expression profile of lncRNAs in embryonic stem (ES) cells, lineage-restricted
      neuronal progenitor cells, and terminally differentiated fibroblasts. In
      addition, we also analyze the relationship between their expression and their
      promoter H3K4 and H3K27 methylation patterns. We find that numerous lncRNAs in
      these cell types undergo changes in the levels of expression and promoter H3K4me3
      and H3K27me3. Interestingly, lncRNAs that are expressed at lower levels in ES
      cells exhibit higher levels of H3K27me3 at their promoters. Consistent with this
      result, knockdown of the H3K27me3 methyltransferase Ezh2 results in derepression
      of these lncRNAs in ES cells. Thus, our results establish a role for Ezh2
      mediated H3K27 methylation in lncRNA silencing in ES cells and reveal that
      lncRNAs are subject to epigenetic regulation in a similar manner to that of the
      protein-coding genes.

PMID- 20680033
TI  - Tom70 imports antiviral immunity to the mitochondria.

PMID- 20680034
TI  - Behavioral and pharmacologic therapies for obesity.
AB  - This article reviews novel developments in the behavioral and pharmacologic
      treatment of obesity and explores the potential contribution of genomics research
      to weight control. A comprehensive program of lifestyle modification, comprised
      of diet, physical activity and behavior therapy, induces a mean loss of 7-10% of
      initial weight in individuals with obesity. Two trials demonstrated that weight
      loss of this magnitude, combined with increased physical activity, substantially
      reduced the risk of developing type 2 diabetes mellitus in individuals with
      impaired glucose tolerance. A third trial is now investigating whether lifestyle
      intervention will reduce cardiovascular morbidity and mortality in overweight
      individuals who already have diabetes mellitus. Pharmacotherapy is recommended,
      in some patients, as an adjunct to lifestyle modification. Two medications
      orlistat and sibutramine-are currently approved in the US for long-term weight
      loss. Both are efficacious when combined with lifestyle modification, although
      health concerns have been raised about the use of sibutramine. Several novel
      combination therapies, which target multiple hypothalamic pathways that regulate
      appetite and body weight, are currently under investigation. Genomic studies
      provide further evidence for the role of these pathways in the regulation of body
      weight. Identification of new genes controlling satiety and energy expenditure
      may yield valuable clues for the development of novel pharmacologic treatments.

PMID- 20680035
TI  - Pitfalls in the use of HbA1(c) as a diagnostic test: the ethnic conundrum.
AB  - The purpose of a diagnostic test is to identify individuals who have a disorder
      and reassure those who do not. An HbA1(c)-based diagnosis of diabetes mellitus or
      prediabetes fails to meet that purpose. Diabetes mellitus is a disorder of
      glucose, not HbA1(c), metabolism. Microvascular complications in diabetes
      mellitus are driven by chronic hyperglycemia. The correlation of these
      complications with HbA1(c) levels is convenient; however, unlike the direct
      information provided by glucose, HbA1(c) values reflect glycemic and nonglycemic
      factors. The latter include modulators of glucose transport across the
      erythrocyte membrane, intracellular protein glycation and deglycation,
      erythrocyte turnover, systemic illness and hematological and medical disorders,
      among others. Genetic rather than glycemic factors explain most of the variance
      in HbA1(c) levels. Finally, HbA1(c) values are misleading as a measure of average
      blood glucose among persons of African, Asian, Hispanic and other non-European
      ancestry. Given the numerous pitfalls, the use of HbA1(c) levels for diagnosing
      diabetes mellitus or prediabetes is ill-advised.

PMID- 20680037
TI  - Pseudonystagmus--clinical features and quantitative characteristics.
AB  - BACKGROUND: A 60 year-old woman with multiple sclerosis (MS) and chronic hearing
      loss presented with head tremor and vestibular hypofunction, the combination of
      which can produce oscillopsia--a visual sensation that steady objects in the
      visual field are oscillating. This case highlights the fact that in patients with
      pseudonystagmus, oscillopsia is attributable to the association of head tremor
      and vestibular hypofunction. INVESTIGATIONS: Eye and head movements were measured
      simultaneously with the search coil technique. DIAGNOSIS: Patients with MS can
      present with oscillopsia, and spontaneous pendular nystagmus is often observed in
      these individuals. In our patient, the oscillopsia was not due to pendular
      nystagmus, but rather to pseudonystagmus (of gaze) resulting from diminished
      compensatory vestibulo-ocular reflex responses to head tremor. MANAGEMENT: A two
      step strategy can be used in patients with pseudonystagmus: pharmacological
      treatment of head tremor, and vestibular rehabilitation to improve balance and
      diminish oscillopsia associated with head movement. Various health-care providers
      at other institutes attempted to address our patient's dystonic head tremor with
      botulinium toxin injections in the neck muscles; the response was unsatisfactory.
      We offered treatment with baclofen, which the patient did not tolerate. We also
      discussed the option of vestibular rehabilitation, which the patient did not
      pursue.

PMID- 20680036
TI  - Neuropsychiatric effects of subthalamic neurostimulation in Parkinson disease.
AB  - Neurostimulation of the subthalamic nucleus (STN) is an established treatment for
      motor symptoms in advanced Parkinson disease (PD), although concerns exist
      regarding the safety of this therapy in terms of cognitive and psychiatric
      adverse effects. The basal ganglia are considered to be part of distributed
      cortico-subcortical networks that are involved in the selection, facilitation and
      inhibition of movements, emotions, behaviors and thoughts. The STN has a central
      role in these networks, probably providing a global 'no-go' signal. The
      behavioral and cognitive effects observed following STN high-frequency
      stimulation (HFS) probably reflect the intrinsic role of this nucleus in nonmotor
      functional domains. Nevertheless, postoperative behavioral changes are seldom
      caused by such stimulation alone. PD is a progressive neurodegenerative disorder
      with motor, cognitive, behavioral and autonomic symptoms. The pattern of
      neurodegeneration and expression of these symptoms are highly variable across
      individuals. The preoperative neuropsychiatric state can be further complicated
      by sensitization phenomena resulting from long-term dopaminergic treatment, which
      include impulse control disorders, punding, and addictive behaviors (dopamine
      dysregulation syndrome). Finally, personality traits, the social environment,
      culture and learned behaviors might be important determinants explaining why
      behavioral symptoms differ between patients after surgery. Here, we summarize the
      neuropsychiatric changes observed after STN HFS and try to disentangle their
      various etiologies.

PMID- 20680038
TI  - Linear, self-referenced technique for single-shot and real-time full
      characterization of (sub-)picosecond optical pulses.
AB  - We propose and experimentally demonstrate single-shot, real-time ultrashort pulse
      intensity and phase characterization using a self-referenced and highly sensitive
      (linear) technique. The proposed method is based on a direct reconstruction of
      the spectral phase of the pulse-under-test (PUT) from three different measured
      spectra, two of which are obtained by a suitable time-synchronized electro-optic
      intensity modulation of the PUT. The required set of spectra are temporally
      interleaved and mapped along the time domain by linear dispersion for single-shot
      acquisition using a real-time scope. A dynamic nonlinear compression experiment
      of a picosecond pulse is fully monitored in real time using the proposed method.

PMID- 20680039
TI  - Influence of dispersion of fiber Bragg grating mirrors on formation of optical
      power spectrum in Raman fiber lasers.
AB  - We show, from experiments and numerical simulations, that dispersion of fiber
      Bragg grating (FBG) mirrors influences the formation of the optical power
      spectrum of Raman fiber lasers by shifting the cavity zero-dispersion wavelength
      inside the FBG reflectivity bandwidth. This results in a spectrum asymmetry,
      which is well described from a master equation including a third-order dispersion
      term.

PMID- 20680040
TI  - Terahertz-wave surface-emitted difference-frequency generation without quasi
      phase-matching technique.
AB  - A scheme of terahertz (THz)-wave surface-emitted difference-frequency generation
      (SEDFG), which lacks the drawbacks associated with the usage of periodically
      orientation-inverted structures, is proposed. It is shown that both material
      birefringence of the bulk LiNbO(3) crystal and modal birefringence of GaAs/AlAs
      waveguide are sufficient to obtain SEDFG up to a frequency of approximately 3THz.
      The simplicity of the proposed scheme, along with the fact that there is a much
      smaller THz-wave decay in nonlinear crystal, makes it a good candidate for the
      practical realization of efficient THz generation. The use of a GaAs waveguide
      with an oxidized AlAs layer is proposed for enhanced THz-wave SEDFG in the
      vicinity of the GaAs polariton resonance at 8THz.

PMID- 20680041
TI  - Use of polycrystalline Nd:YAG rods to achieve pure radially or azimuthally
      polarized beams from high-average-power lasers.
AB  - We report maintenance of perfect radial-polarization purity in high-power, cw
      pump chambers using strengthened, polycrystalline Nd:YAG laser rods. Although the
      cubic symmetry of single-crystal rods caused threefold symmetric birefringence
      due to shear stresses at the ends of the pumped zone, polycrystalline rods
      macroscopically behaved as isotropic material and enabled polarization
      preservation. Elimination of this source of depolarization prevents the major
      source of bifocusing aberrations in a chain of amplifiers.

PMID- 20680042
TI  - Precise detection of two-dimensional displacement based on nonlinear lateral
      photovoltaic effect.
AB  - Although the lateral photovoltaic effect (LPE) can be used to detect very small
      displacement owing to its linear characteristic of the lateral photovoltage (LPV)
      response to laser position, the effective measurement is limited only within the
      one-dimensional (1D) region between two contacts. In this work, we report a way
      to detect two-dimensional (2D) displacement based on a nonlinear LPE in a metal
      semiconductor (MS) structure. In addition, compared with the conventional 1D
      method, this 2D detection possesses a much higher precision owing to its
      independence of LPV sensitivity of the structure, indicating it as a candidate
      for the new type of MS-based 2D photoelectric devices.

PMID- 20680043
TI  - Dynamic tuning of an optical resonator through MEMS-driven coupled photonic
      crystal nanocavities.
AB  - We present dynamic tuning of optical resonance using microelectromechanical
      systems (MEMS)-driven coupled photonic crystal (PhC) nanocavities. The device
      consists of an air-suspended one-dimensional PhC nanocavity coupled to input and
      output waveguides and a perturbing nanocavity attached to a submicrometer MEMS
      comb drive. Resonance tuning is achieved through varying the gap between the two
      coupled cavities. We demonstrate experimentally that resonance can be tuned up to
      8nm with no significant deterioration in the Q factor. The proposed mechanism
      potentially enables a new platform of on-chip photonic devices that can achieve a
      large tuning range with low power and small footprint and may find useful
      applications in tunable optical/photonic devices.

PMID- 20680044
TI  - Nematicons beyond the perturbative regime.
AB  - We model spatial solitons in nematic liquid crystals, accounting for
      nonperturbative excitation and related effects, such as power-dependent self
      steering. We also address the interplay between nonlocality and saturation
      typical of a reorientational medium.

PMID- 20680045
TI  - Refractive index sensing with an air-slot photonic crystal nanocavity.
AB  - We investigate an air-slot photonic crystal cavity for high-precision refractive
      index sensing. The high quality factor approximately 2.6x10(4) of the cavity,
      along with a strong overlap between the resonant mode and the hollow core region,
      allows us to achieve an experimental sensitivity of 510nm per refractive index
      unit (RUI) and a detection limit below 1x10(-5)RUI. The device has a remarkably
      low sensing volume of 40aliters, holding less than 1x10(6)molecules.

PMID- 20680046
TI  - Refractive index engineering with subwavelength gratings for efficient
      microphotonic couplers and planar waveguide multiplexers.
AB  - We use subwavelength gratings (SWGs) to engineer the refractive index in
      microphotonic waveguides, including practical components such as input couplers
      and multiplexer circuits. This technique allows for direct control of the mode
      confinement by changing the refractive index of a waveguide core over a range as
      broad as 1.6-3.5 by lithographic patterning. We demonstrate two experimental
      examples of refractive index engineering, namely, a microphotonic fiber-chip
      coupler with a coupling loss as small as -0.9dB and minimal wavelength dependence
      and a planar waveguide multiplexer with SWG nanostructure, which acts as a slab
      waveguide for light diffracted by the grating, while at the same time acting as a
      lateral cladding for the strip waveguide. This yields an operation bandwidth of
      170nm for a device size of only approximately 160microm x100microm.

PMID- 20680047
TI  - Solitary pulse propagation and soliton-induced supercontinuum generation in
      silica glasses containing silver nanoparticles.
AB  - We study solitary pulse propagation in the normal dispersion region in glasses
      containing silver nanoparticles with a self-defocusing nonlinearity and predict
      that, despite high plasmonic loss, pulse propagation without significant
      distortion over five soliton periods can be achieved in such materials. As an
      application, we study low-threshold soliton-induced supercontinuum generation and
      predict more than octave-spanning spectral broadening by femtosecond pulses with
      an intensity in the range of hundreds of GW/cm(2).

PMID- 20680048
TI  - Terahertz spectrum analyzer based on frequency and power measurement.
AB  - We demonstrate a terahertz (THz) spectrum analyzer based on frequency and power
      measurement. A power spectrum of a continuous THz wave is measured through
      optical heterodyne detection using an electromagnetic THz frequency comb and a
      bolometer and power measurement using a bolometer with a calibrated responsivity.
      The THz spectrum analyzer has a frequency precision of 1x10(-11), a frequency
      resolution of 1Hz, a frequency band up to 1.7THz, and an optical noise equivalent
      power of approximately 1 pW/Hz(1/2).

PMID- 20680049
TI  - Design of low-threshold compact Au-nanoparticle lasers.
AB  - We performed a rigorous study to reduce threshold gain of Au-nanoparticle lasers
      in the deep-subwavelength scale with the consideration of strong interband
      transitions in Au and device dimensions. We found that the high-threshold optical
      gain of the nanolaser (over 10(5)cm(-1), which is matched with the result
      estimated from a previous article [Nature 460, 1110 (2009)]) arises from the high
      interband transition of Au near 530nm. It can be shown that by increasing the
      background index, as well as optimizing the lasing wavelength and device
      dimensions, the threshold gain (cavity volume) can be reduced by 43% (90%).

PMID- 20680050
TI  - Predicting laser-induced bulk damage and conditioning for deuterated potassium
      dihydrogen phosphate crystals using an absorption distribution model.
AB  - We present an empirical model that describes the experimentally observed laser
      induced bulk damage and conditioning behavior in deuterated potassium dihydrogen
      phosphate (DKDP) crystals. The model expands on an existing nanoabsorber
      precursor model and the multistep absorption mechanism to include two populations
      of absorbing defects, one with linear absorption and another with nonlinear
      absorption. We show that this model connects previously uncorrelated small-beam
      damage initiation probability data to large-beam damage density measurements over
      a range of nanosecond pulse widths. In addition, this work predicts the damage
      behavior of laser-conditioned DKDP.

PMID- 20680051
TI  - Modified self-deconvolution restoration algorithm for adaptive-optics solar
      images.
AB  - The correction conducted by adaptive optics (AO) is partially due to limitations
      of the hardware. A postprocessing method, such as blind deconvolution, is used to
      improve image quality. In this Letter, a modified self-deconvolving data
      reconstruction algorithm, in which the information recorded by the wavefront
      sensor in closed-loop status is applied to estimate the deconvolution operator,
      is proposed for AO image deconvolution. This method is applied in deconvolving
      solar images captured by a 37-element AO system. The result shows that the method
      is efficient for improving image quality corrected by AO.

PMID- 20680052
TI  - Photoluminescence of Sr(2)P(2)O(7):Bi(2+) as a red phosphor for additive light
      generation.
AB  - We report on photoluminescence of Sr(2)P(2)O(7):Bi(2+) as a potential red
      emitting phosphor for multichromatic light sources. If excited with blue light,
      photoluminescence of this compound spans the spectral range of about 600 to
      760nm. Static and dynamic spectral data reveal the presence of two distinct
      emission centers. Based on bond covalency and emission lifetime, luminescence can
      clearly be assigned to Bi(2+) ions on Sr(1) and Sr(2) lattice sites,
      respectively. Energy transfer is observed from Bi(1) to Bi(2). Transfer
      efficiency, estimated from the lifetimes of the excited states, increases with
      increasing dopant concentration.

PMID- 20680053
TI  - Ultraviolet excitation of remote phosphor with symmetrical illumination used in
      dual-sided liquid-crystal display.
AB  - The UV-excited flat lighting (UFL) technique differs from conventional
      fluorescent lamp or LED illumination. It involves using a remote phosphor film to
      convert the wavelength of UV light to visible light, achieving high brightness
      and planar and uniform illumination. In particular, UFL can accomplish compact
      size, low power consumption, and symmetrical dual-sided illumination.
      Additionally, UFL utilizes a thermal radiation mechanism to release the large
      amount of heat that is generated upon illumination without thermal accumulation.
      These characteristics of the UFL technique can motivate a wide range of lighting
      applications in thin-film transistor LCD backlighting or general lighting.

PMID- 20680054
TI  - Femtosecond filamentation in air and higher-order nonlinearities.
AB  - According to a recent experiment, the instantaneous electronic Kerr effect in air
      exhibits a strong intensity dependence, the nonlinear refractive index switching
      sign and crossing over from a self-focusing to a defocusing nonlinearity. A
      subsequent theoretical work has demonstrated that this has paradigm-changing
      consequences for the understanding of filamentation in air, so it is important to
      subject the idea of higher-order nonlinearities to stringent tests. Here we use
      numerical modeling to propose an experiment capable of discriminating between the
      standard and the new intensity-dependent Kerr-effect models.

PMID- 20680055
TI  - Simultaneous Raman and elastic light scattering imaging for particle formation
      investigation.
AB  - We used two-dimensional laser Raman scattering and elastic light scattering to
      analyze mixture driven particle formation in the supercritical antisolvent
      process. Using only one excitation laser, the partial density of the antisolvent
      CO(2), the composition of the solvent/antisolvent mixture, and the occurrence of
      particle formation can be analyzed simultaneously. Thus, all main parameters that
      influence the process of particle formation and, subsequently, the desired
      properties of the produced powder are accessible.

PMID- 20680056
TI  - Pr:YAlO(3) microchip laser.
AB  - A cw Pr:YAlO(3) microchip-laser operation in the near-IR spectral region is
      reported. A microchip resonator was formed by dielectric mirrors directly
      deposited on the Pr:YAlO(3) crystal surfaces. For active medium pumping, a GaN
      laser diode providing up to 1W of output power at approximately 448 nm was used.
      139mW of laser radiation at 747nm wavelength has been extracted from the
      microchip-laser system. Slope efficiency related to the incident pumping power
      was approximately 25%.

PMID- 20680058
TI  - Temporal dynamics of two-photon-pumped amplified spontaneous emission in slab
      organic crystals.
AB  - We have studied the ultrafast dynamics of two-photon-pumped amplified spontaneous
      emission (ASE) from a single crystal by the time-resolved fluorescence
      upconversion technique. With the increase of two-photon pump intensities, the
      emission decay time is dramatically shortened by 30 times (from 3ns to
      approximately 87 ps), and the energy migration rate is acutely enhanced when ASE
      occurs. The stripe length is also found to play an important role in the
      formation of the ASE. Meanwhile, the gain coefficient is evaluated to be 15cm(-1)
      for 560nm at an excitation intensity of 2.3mJ/pulse/cm(2) by the variable stripe
      length technique.

PMID- 20680057
TI  - High-speed multispectral fluorescence lifetime imaging implementation for in vivo
      applications.
AB  - Fluorescence lifetime imaging microscopy (FLIM) offers a noninvasive approach for
      characterizing the biochemical composition of biological tissue. In recent years,
      there has been an increasing interest in the application of multispectral FLIM
      for medical diagnosis. Central to the clinical translation of FLIM technology is
      the development of robust, fast, and cost-effective FLIM instrumentation suitable
      for in vivo tissue imaging. Unfortunately, the predominant multispectral FLIM
      approaches suffer from limitations that impede the development of high-speed
      instruments for in vivo applications. We present a cost-effective scanning
      multispectral FLIM implementation capable of achieving pixel rates on the order
      of tens of kilohertz, which will facilitate the evaluation of FLIM for in vivo
      applications.

PMID- 20680059
TI  - Broadband infrared mirror using guided-mode resonance in a subwavelength
      germanium grating.
AB  - We demonstrate a broadband mirror for the IR wavelength region comprising a
      subwavelength grating made of germanium. We design and optimize the guided-mode
      resonances in the structure for TM-polarized incident light by rigorous
      electromagnetic simulations. The grating structure is realized by nanoimprint
      lithography and dry etching. The reflectivity of the mirror is over 95% for the
      wavelength range between 2245 and 3080nm.

PMID- 20680060
TI  - Unidirectional ring-laser operation using sum-frequency mixing.
AB  - A technique enforcing unidirectional operation of ring lasers is proposed and
      demonstrated. The approach relies on sum-frequency mixing between a single-pass
      laser and one of the two counterpropagating intracavity fields of the ring laser.
      Sum-frequency mixing introduces a parametric loss for the intracavity field
      copropagating with the single-pass field, effectively generating a loss
      difference between the copropagating and counterpropagating intracavity fields.
      This loss mechanism ensures stable unidirectional lasing. The approach is generic
      and can be implemented at any desired lasing wavelength where lossless second
      order nonlinear materials are available. Numerical modeling and experimental
      demonstration of parametric-induced unidirectional operation of a diode-pumped
      solid-state 1342nm cw ring laser are presented.

PMID- 20680061
TI  - Polarimetry-based method to extract geometry-independent metrics of tissue
      anisotropy.
AB  - Recently, we have used polarimetry as a method for assessing the linear
      retardance of infarcted myocardium. While linear retardance reflects tissue
      anisotropy, experimental geometry has a confounding effect due to dependence of
      the linear retardance on the orientation of the sample with respect to the
      probing beam. Here, polarimetry imaging of an 8mm diameter birefringent
      polystyrene sphere of known anisotropy axis was used to test a dual-projection
      method by which the anisotropy axis and its true magnitude can be reconstructed,
      thus eliminating the confounding effect of anisotropy axis orientation.
      Feasibility is demonstrated in ex-vivo tissue imaging.

PMID- 20680062
TI  - Plasmon resonances on gold nanowires directly drawn in a step-index fiber.
AB  - We report the successful production of high-quality gold wires, with diameters
      down to 260nm, by direct fiber drawing from a gold-filled fused-silica cane. The
      stack-and-draw technique makes it straightforward to incorporate a conventional
      step-index core, adjacent to the gold wire, in the cane. In the drawn fiber,
      strong coupling of light from the glass core to SPP resonances on the gold wire
      is observed at specific well-defined wavelengths. Such embedded wires have many
      potential applications, for example, as nanoscale electrodes, in nonlinear
      optical plasmonics, and as near-field scanning optical microscope tips.

PMID- 20680063
TI  - Optical properties of silver nanowire arrays with 35 nm periodicity.
AB  - We present highly ordered Ag nanowire arrays with 35nm periodicity grown on
      patterned templates. The optical properties measured using generalized
      ellipsometry exhibit strong anisotropy. Dielectric functions are calculated by
      fitting the Jones matrix elements with a biaxial layer model, accounting for both
      metallic behavior and localized surface plasmon resonances. The amplitude and
      wavelength maximum of the plasmon resonance perpendicular to the wires increase
      with increasing wire width and thickness. The dielectric coefficients of 10-mm
      wide nanowires show a transition behavior from insulating in UV to metallic above
      550nm. Their potential application as polarization-dependent plasmonic-scattering
      transparent conductive electrodes is discussed.

PMID- 20680064
TI  - Twisted chains of resonant particles: optical polarization control, waveguidance,
      and radiation.
AB  - Linear chains of metallic nanoparticles that are sequentially rotated about the
      chain axis display interesting polarization-sensitive optical properties. Such
      twisted chains posses and extend properties of chiral gratings and general
      periodic gratings. They are characterized by high anisotropy and polarization
      sensitivity, and have subwavelength transverse dimensions. These structures are
      shown to support transverse modes with distinct propagation wavenumbers and
      radiation properties, including slow (bound) and fast (radiative) modes. They
      also have stop bands of different types, resulting from coupling between distinct
      transverse modes, as well as coupling with different higher-order diffraction
      modes.

PMID- 20680065
TI  - Nonmechanical bifocal zoom telescope.
AB  - We report on a novel zoom lens with no moving parts in the form of a switchable
      Galilean telescope. This zoom telescope consists of two flat liquid-crystal
      diffractive lenses with apertures of 10mm that can each take on the focal lengths
      of -50 and +100cm, with a spacing of 50cm and, hence, a zoom ratio of 4x. The
      lenses are driven using a low-voltage ac source with 1.6V and exhibit millisecond
      switching times. The spectral characteristic of this diffractive zoom system is
      evaluated for light sources of various bandwidths. Potential applications for
      this technology include a zoom lens with no moving parts for camera phones and
      medical imaging devices.

PMID- 20680066
TI  - Optical ptychography: a practical implementation with useful resolution.
AB  - Quantitative phase microscopy offers a range of benefits over conventional phase
      contrast techniques. For example, changes in refractive index and specimen
      thickness can be extrapolated and images can be refocused subsequent to their
      recording. In this Letter, we detail a lensless, quantitative phase microscope
      with a wide field of view and a useful resolution. The microscope uses the
      recently reported coherent diffractive imaging technique of ptychography to
      generate images from recorded diffraction patterns.

PMID- 20680067
TI  - Ultrabroadband optical circular polarizers consisting of double-helical nanowire
      structures.
AB  - Recently, it was demonstrated by Gansel et al. [Science 325, 1513 (2009)] that 3D
      single-helical metamaterials can serve as broadband circular polarizers in the IR
      range. In this study, we propose a structured metamaterial with double-helical
      nanowires to construct circular polarizers with boarder wavelength bands in the
      visible-light and near-IR regions. Using the finite-difference time-domain
      method, we confirmed that the circular polarizers with the double-helical
      structures have operation bands more than 50% broader than those of the single
      helical structures.

PMID- 20680068
TI  - Frequency downconversion for a quantum network.
AB  - By using a parametric downconversion process with a strong signal field
      injection, we demonstrate coherent frequency downconversion from a pump photon to
      an idler photon. Contrary to a common misunderstanding, we show that the process
      can be free of quantum noise. With an interference experiment, we demonstrate
      that the coherence is preserved in the conversion process. This may lead to a
      high-fidelity quantum state transfer from a high-frequency photon to a low
      frequency photon and connects a missing link in a quantum network. With this
      scheme of coherent frequency downconversion of photons, we propose a method of
      single-photon WDM.

PMID- 20680069
TI  - Experimental demonstration of an ultracompact Si-nanowire-based reflective
      arrayed-waveguide grating (de)multiplexer with photonic crystal reflectors.
AB  - An ultracompact reflective arrayed-waveguide grating (AWG) (de)multiplexer based
      on Si nanowires is demonstrated for the first time (to our knowledge). Each
      waveguide in the array has an individual photonic crystal (PhC) reflector at its
      end, making the AWG layout design very flexible. An eight-channel AWG
      (de)multiplexer with a channel spacing of 400 GHz is demonstrated experimentally.
      The total size of the fabricated AWG is as small as 134mumx115mum. The excess
      loss of the fabricated reflective AWG (de)multiplexer is about 3-4 dB, and the
      crosstalk is about -12dB.

PMID- 20680070
TI  - One-way transmission through the subwavelength slit in nonsymmetric metallic
      gratings.
AB  - An approach for obtaining one-way transmission in the beaming regime is suggested
      that is based on the directional radiation of surface plasmons in nonsymmetric
      metallic gratings with a single slit. In contrast to the various nonsymmetric one
      way diffraction gratings that have recently been proposed, the possibility of
      obtaining of narrow beams is demonstrated. Strong directional selectivity can
      appear a wide range of the observation angles, while the angle of incidence is
      retained.

PMID- 20680071
TI  - Comparison of maximal achievable contrast in scalar, Stokes, and Mueller images.
AB  - We compare the performances of three different polarimetric imaging modalities,
      scalar, Stokes, and Mueller, in terms of achievable contrast for target detection
      applications. These modalities require, respectively, 1, 4, and 16 intensity
      measurements to form the polarimetric image. We show that the technique that
      leads to the best contrast is the scalar one, which requires only one optimized
      measurement.

PMID- 20680072
TI  - Controlling mode degeneracy in a photonic crystal nanocavity with infiltrated
      liquid crystal.
AB  - We demonstrate the control of the mode degeneracy when a liquid crystal (LC) is
      infiltrated into an InGaAsP membrane photonic crystal nanocavity with embedded
      InAs quantum dots. Mode splitting exists in the anisotropic nematic LC state, and
      not in the unfilled or isotropic LC state. The degeneracy lifting of the
      quadrupole mode is attributed to the different interactions of the two orthogonal
      basis modes of the degenerate mode with the two components of the refractive
      index of the LC. The interpretation is supported by the quantitative agreement
      between the experimental results and the three-dimensional finite-difference time
      domain computations.

PMID- 20680073
TI  - Two-dimensionally tunable microwave signal generation based on optical frequency
      to-time conversion.
AB  - We propose and experimentally demonstrate an all-fiber-based approach to generate
      microwave signals with tunable frequency and pulse width. The adjustable optical
      power spectrum can be achieved using a spectrum shaper, consisting of a variable
      differential-group-delay element and a bandwidth-tunable optical filter. Through
      the frequency-to-time conversion in the dispersive fiber, the frequency and pulse
      width of the obtained microwave signals can be user defined by modifying the
      optical spectrum shape.

PMID- 20680074
TI  - High-energy, in-band pumped Q-switched Ho(3+):LuLiF(4) 2 microm laser.
AB  - A Q-switched Tm:fiber-laser-pumped Ho:LuLiF(4) laser is reported that has been
      optimized for high-energy pulses at low repetition rates. Operating at 100Hz, a
      pulse energy of 24.8mJ with pulse widths of 47ns at a wavelength of 2052nm was
      achieved. The beam propagation factor (M(2)) was measured to be approximately
      1.04 at the maximum pump power, confirming fundamental transverse mode (TEM(00))
      operation. Starting the pump laser at maximum power, the pulse energies of each
      of the first 10 pulses are >47mJ. This strong influence of crystal temperature on
      laser performance is discussed with the prospect for further improvement of the
      laser efficiency.

PMID- 20680075
TI  - Simultaneous two-wavelength transmission quantitative phase microscopy with a
      color camera.
AB  - We present a quantitative phase microscopy method that uses a Bayer mosaic color
      camera to simultaneously acquire off-axis interferograms in transmission mode at
      two distinct wavelengths. Wrapped phase information is processed using a two
      wavelength algorithm to extend the range of the optical path delay measurements
      that can be detected using a single temporal acquisition. We experimentally
      demonstrate this technique by acquiring the phase profiles of optically clear
      microstructures without 2pi ambiguities. In addition, the phase noise
      contribution arising from spectral channel crosstalk on the color camera is
      quantified.

PMID- 20680076
TI  - High-efficiency 5000 lines/mm multilayer-coated blazed grating for extreme
      ultraviolet wavelengths.
AB  - Volume x-ray gratings consisting of a multilayer coating deposited on a blazed
      substrate can diffract with very high efficiency, even in high orders if
      diffraction conditions in-plane (grating) and out-of-plane (Bragg multilayer) are
      met simultaneously. This remarkable property, however, depends critically on the
      ability to create a structure with near atomic perfection. In this Letter we
      report on a method to produce these structures. We report measurements that show,
      for a 5000l/mm grating diffracting in the third order, a diffraction efficiency
      of 37.6% at a wavelength of 13.6nm. This work now shows a direct route to
      achieving high diffraction efficiency in high order at wavelengths throughout the
      soft x-ray energy range.

PMID- 20680077
TI  - Nonadiabatic propagation effect for generating isolated sub-100 as pulses in the
      high-order harmonic plateau.
AB  - A robust scheme is proposed to generate an isolated sub-100 as pulse by using a
      5fs/800nm driving pulse in combination with a macroscopic propagation effect. We
      demonstrate that one of the generated attosecond bursts in the high-order
      harmonic plateau can be efficiently dominant only when both the gas pressure and
      the gas cell length are properly chosen. We also show that this method can relax
      the dependence on the stabilization of the carrier-envelope phase (CEP) of the
      driving pulse. A single sub-100as pulse with only 10as duration variation can be
      produced even for about 50% fluctuation of the CEP. Under optimized conditions,
      an isolated 60as pulse can be directly generated without any additional phase
      compensation.

PMID- 20680078
TI  - Ultrahigh-sensitivity single-photon detection with linear-mode silicon avalanche
      photodiode.
AB  - We developed an ultrahigh-sensitivity single-photon detector using a linear-mode
      avalanche photodiode (APD) with a cryogenic low-noise readout circuit; the APD is
      operated at 78K. The noise-equivalent power of the detector is as low as 2.2x10(
      20)W/Hz(1/2) at a wavelength of 450nm. The photon-detection efficiency and dark
      count rate (DCR) are 0.72 and 0.0008counts/s, respectively. A low DCR is achieved
      by thermal treatment for reducing the trapped carriers when the thermal treatment
      temperature is above 100K.

PMID- 20680080
TI  - Photon-counting 1.55 microm optical communications with pulse-position modulation
      and a multimode upconversion single-photon receiver.
AB  - We report single-photon frequency upconversion of multimode light from 1.55 to
      0.532microm and demonstrate an end-to-end optical link that emulates photon
      starved communications and atmospheric propagation. Using 64-ary pulse-position
      modulation and a half-rate serially concatenated turbo code we achieve a decoded
      efficiency of 0.3 detected photons/bit.

PMID- 20680079
TI  - Random laser spectroscopy for nanoscale perturbation sensing.
AB  - We report a spectroscopic method using coherent random lasers for a simple, yet
      nanoscale, sensing approach. Unique spectral properties of coherent random laser
      emission can be detectably altered when introducing nanoscale perturbations to a
      simple nanocomposite film that consists of dielectric nanospheres and laser-dye
      doped polymer to serve as a transducer. Random lasing action provides a means to
      amplify subtle perturbations to readily detectable spectral shifts in multiple
      discrete emission peaks. Owing to several advantages, such as large-area
      detection, narrow and multiple emission peaks, straightforward detection, and
      simple fabrication, random laser spectroscopy has the potential for
      ultrasensitive, yet simple, biosensors in various applications.

PMID- 20680081
TI  - Optimized logarithmic phase masks used to generate defocus invariant modulation
      transfer function for wavefront coding system.
AB  - In a previous Letter [Opt. Lett. 33, 1171 (2008)], we proposed an improved
      logarithmic phase mask by making modifications to the original one designed by
      Sherif. However, further studies in another paper [Appl. Opt. 49, 229 (2010)]
      show that even when the Sherif mask and the improved one are optimized, their
      corresponding defocused modulation transfer functions (MTFs) are still not stable
      with respect to focus errors. So, by further modifying their phase profiles, we
      design another two logarithmic phase masks that exhibit more stable defocused
      MTF. However, with the defocus-induced phase effect considered, we find that the
      performance of the two masks proposed in this Letter is better than the Sherif
      mask, but worse than our previously proposed phase mask, according to the Hilbert
      space angle.

PMID- 20680082
TI  - Parallel detection of amplitude-modulated, ultrasound-modulated optical signals.
AB  - We investigated the effect of amplitude-modulated (AM) ultrasound (US) on acousto
      optic (AO) signals. A phantom was exposed to both AM US and a green laser, and
      CCD measurements of speckle contrast were made with various exposure times. The
      results show that the AO signal oscillates at the AM frequency when the CCD
      exposure time is a fraction of the AM period and stops oscillating when the CCD
      exposure time is a multiple of the AM period. The AO signal decreases quickly as
      the AM frequency increases or peak-peak (pk-pk) amplitude decreases. With 4ms
      exposure time, 250Hz AM frequency and 1.27MPa pk-pk acoustic pressure, there is
      an ~30% increase in the AO signal compared with that of CW US. The increase in
      the signal is likely to be due to the particle oscillation and the induced shear
      wave as a result of the radiation force generated by the AM US.

PMID- 20680083
TI  - Improving weak-signal identification via predetection background suppression by a
      pixel-level, surface-wave enabled dark-field aperture.
AB  - We report the successful implementation of a surface-wave enabled dark-field
      aperture (SWEDA) directly on a complementary metal-oxide semiconductor sensor
      pixel (2.2mum). This SWEDA pixel allows predetection cancellation of a uniform
      coherent background. We show that the signal-to-noise ratio (SNR) of the SWEDA
      pixel is better than that of a single undressed pixel over a significant range of
      signal-to-background ratio (SBR). For a small SBR value (SBR=0.001, background
      intensity=3.96W/m(2), integration time=5ms), we further demonstrate that a SWEDA
      pixel can detect a weak localized signal buried in a high background, while
      conventional postdetection background subtraction cannot (improved SNR=2.2 versus
      SNR=0.26).

PMID- 20680084
TI  - Physical insight into light scattering by photoreceptor cell nuclei.
AB  - A recent study showed that the rod photoreceptor cell nuclei in the retina of
      nocturnal and diurnal mammals differ considerably in architecture: the location
      of euchromatin and heterochromatin in the nucleus is interchanged. This inversion
      has significant implications for the refractive index distribution and the light
      scattering properties of the nucleus. Here, we extend previous two-dimensional
      analysis to three dimensions (3D) by using both a numerical finite-difference
      time-domain and an analytic Mie theory approach. We find that the specific
      arrangement of the chromatin phases in the nuclear core-shell models employed
      have little impact on the far-field scattering cross section. However, scattering
      in the near field, which is the relevant regime inside the retina, shows a
      significant difference between the two architectures. The "inverted"
      photoreceptor cell nuclei of nocturnal mammals act as collection lenses, with the
      lensing effect being much more pronounced in 3D than in two dimensions. This
      lensing helps to deliver light efficiently to the light-sensing outer segments of
      the rod photoreceptor cells and thereby improve night vision.

PMID- 20680085
TI  - Distributed external cloak without embedded antiobjects.
AB  - We propose a distributed external cloak without embedded antiobjects, which
      contains tunable windows and a cloaking area. It consists of closed and
      standalone systems whose positions and parameters can be separately controlled by
      the design purpose and folded geometry. Such an external cloak does not rely on
      either cloaked material or the concept of the antiobject [Phys. Rev. Lett. 102,
      093901 (2009)] in the complementary material, and can thus be kept unchanged when
      different objects are considered. The object lies outside the cloak and is not
      blinded in terms of multiple open windows desired by specific designs. Such a
      distributed cloak enables us to conceal arbitrary objects of varying shape in
      center areas, which may exceed the inner boundary of a perfect closed cloak.

PMID- 20680086
TI  - Single-cycle multiterahertz transients with peak fields above 10 MV/cm.
AB  - Phase-locked single-cycle transients with frequency components between 1 and
      60THz and peak fields of up to 12MV/cm are generated as the idler wave of a
      parametric amplifier. To achieve broadband conversion in GaSe nonlinear crystals,
      we match the group velocities of signal and idler components. The influence of
      group-velocity dispersion is minimized by long-wavelength pumping at 1.18mum.
      Free-space electro-optic sampling monitors the multiterahertz waveforms with
      direct field resolution.

PMID- 20680087
TI  - Bidirectional mode-locked fiber ring laser using self-regenerative, passively
      controlled, threshold gating.
AB  - We demonstrate a technique to achieve bidirectional mode locking of a fiber ring
      laser using two amplitude modulators passively driven by a signal regenerated
      from the oscillation of the laser itself. The new scheme allows generation of two
      independent-frequency unlocked-countercirculating pulses and active control of
      their crossing points. The technique minimizes the effects of the dead band
      associated with crossing at a scattering media. Results show stable bidirectional
      pulses at a 5MHz repetition rate with no detectable dead band.

PMID- 20680088
TI  - Exact spatial similaritons and rogons in 2D graded-index waveguides.
AB  - We analytically obtain both bright and dark spatial similaritons on the
      background wave and rogons in two-dimensional (2D) graded-index waveguides.

PMID- 20680089
TI  - Real-time synchronous imaging of electromechanical resonator mode and equilibrium
      profiles.
AB  - Interferometric imaging of normal mode dynamics in electromechanical resonators,
      oscillating in the rf regime, is demonstrated by synchronous imaging with a
      pulsed nanosecond laser. Profiles of mechanical modes in suspended thin film
      structures and their equilibrium profiles are measured through all-optical Fabry
      Perot reflectance fits to the temporal traces. As a proof of principle, the mode
      patterns of a microdrum silicon resonator are visualized, and the extracted
      vibration modes and equilibrium profile show good agreement with numerical
      estimations.

PMID- 20680090
TI  - Location of hot spots in integrated circuits by monitoring the substrate thermal
      phase lag with the mirage effect.
AB  - This Letter presents a solution for locating hot spots in active integrated
      circuits (IC) and devices. This method is based on sensing the phase lag between
      the power periodically dissipated by a device integrated in an IC (hot spot) and
      its corresponding thermal gradient into the chip substrate by monitoring the heat
      induced refractive index gradient with a laser beam. The experimental results
      show a high accuracy and prove the suitability of this technique to locate and
      characterize devices behaving as hot spots in current IC technologies.

PMID- 20680091
TI  - Efficient beam converter for the generation of high-power femtosecond vortices.
AB  - We describe an optical beam converter for an efficient transformation of Gaussian
      femtosecond laser beams to single- or double-charge vortex beams. The device
      achieves a conversion efficiency of 75% for single- and 50% for double-charge
      vortex beams and can operate with high-energy broad bandwidth pulses. We also
      show that the topological charge of a femtosecond vortex beam can be determined
      by analyzing its intensity distribution in the focal area of a cylindrical lens.

PMID- 20680092
TI  - Prospects of molecular photoacoustic imaging at 1064 nm wavelength.
AB  - An analysis of the photoacoustic (PA) signal from murine tissue in vivo revealed
      several benefits of contrast-enhanced PA imaging at a wavelength of 1064nm. Of
      all the wavelengths tested in a range from 710 to 1064nm, the background PA
      signal from tissue in vivo was lowest and more homogeneous at 1064nm. For blood
      laden tissue, the background PA signal was up to 70% less at 1064nm. Furthermore,
      when plasmonic nanoparticles, such as silver nanoplates, were introduced in vivo
      as contrast agents, the contrast in PA images at 1064nm increased 38% compared to
      750nm. Therefore, contrast-enhanced PA imaging at 1064nm is advantageous because
      of the low and homogeneous signal from native tissue, enabling high contrast in
      PA imaging when exogenous, molecularly targeted agents are employed.

PMID- 20680093
TI  - High-power disordered Nd:CaYAlO(4)lasers at 1.08 microm.
AB  - We demonstrate the high-power laser performance with a disordered Na:CaYAlO(4)
      crystal at a wavelength of about 1.08microm. Continuous-wave output power of
      5.16W is achieved with a laser diode as the pump source. For the first time to
      our knowledge, the passively Q-switched Na:CaYAlO(4) laser is obtained with the
      maximum average output power of 2.39W, shortest pulse width of 5.7ns, and highest
      peak power of 15.47kW. By spectral analysis, the Nd:CaAlO(4) laser wavelength is
      centered at about 1.08microm. We propose that, by suitable tuning, the
      Na:CaYAlO(4) laser should be an excellent source for helium optical pumping.

PMID- 20680094
TI  - Differential gene expression in bacterial symbionts from loliginid squids
      demonstrates variation between mutualistic and environmental niches.
AB  - Luminescent bacteria (gamma-Proteobacteria: Vibrionaceae) are found in complex
      bilobed light organs of both sepiolid and loliginid squids (Mollusca:
      Cephalopoda). Despite the existence of multiple strain colonization between
      Vibrio bacteria and loliginid squids, specificity at the genus level still exists
      and may influence interactions between symbiotic and free-living stages of the
      symbiont. The environmentally transmitted behaviour of Vibrio symbionts bestows a
      certain degree of recognition that exists prior and subsequent to the
      colonization process. Therefore, we identified bacterial genes required for
      successful colonization of loliginid light organs by examining transcripts solely
      expressed in either the light organ or free-living stages. Selective capture of
      transcribed sequences (SCOTS) was used to differentiate genes expressed by the
      same bacterium when thriving in two different environments (i.e. loliginid light
      organs and seawater). Genes specific for squid light organs included vulnibactin
      synthetase, outer membrane protein W and dihydroxy dehydratase, which have been
      associated with the maintenance of bacterial host associations in other systems.
      In contrast, genes that were solely expressed in the free-living condition
      consisted of transcripts recognized as important factors for bacterial survival
      in the environment. These transcripts included genes for methyl accepting
      chemotaxis proteins, arginine decarboxylase and chitinase. These results provide
      valuable information regarding mechanisms determining specificity, establishment,
      and maintenance of bacteria-squid associations.

PMID- 20680096
TI  - Nanopore fabrication in amorphous Si: Viscous flow model and comparison to
      experiment.
AB  - Nanopores fabricated in free-standing amorphous silicon thin films were observed
      to close under 3 keV argon ion irradiation. The closing rate, measured in situ,
      exhibited a memory effect: at the same instantaneous radius, pores that started
      larger close more slowly. An ion-stimulated viscous flow model is developed and
      solved in both a simple analytical approximation for the small-deformation limit
      and in a finite element solution for large deformations. The finite-element
      solution exhibits surprising changes in cross-section morphology, which may be
      extremely valuable for single biomolecule detection, and are untested
      experimentally. The finite-element solution reproduces the shape of the measured
      nanopore radius versus fluence behavior and the sign and magnitude of the
      measured memory effect. We discuss aspects of the experimental data not
      reproduced by the model, and successes and failures of the competing adatom
      diffusion model.

PMID- 20680095
TI  - Targeted Therapies in Lung Cancer.
AB  - An ongoing research and multiple clinical trials involve new targeted therapies
      and less aggressive treatment regimens that improve survival in patients with
      lung cancer. Targeted therapeutic agents are based on the concept of discovering
      genetic alterations and the signaling pathways altered in cancer and have added
      significantly to our armamentarium in order to prolong patient survival and
      minimizing drug toxicity. Among 34 molecularly targeted drugs approved by U.S.
      Food and Drug Administration (FDA) for treatment of various cancers since 1998
      three targeted therapies have been approved for treatment of lung cancer
      (gefitinib in 2002, erlotinib in 2003, and bevacizumab in 2006).This review
      focuses on the targeted therapies in lung cancer, the molecular biomarkers that
      help identify patients that will benefit for these targeted therapies, describes
      the basic molecular biology principles and selected molecular diagnostic
      techniques and the pathological features correlated with molecular abnormalities
      in lung cancer. Lastly, new molecular abnormalities described in lung cancer that
      are predictive to novel promising targeted agents in various phases of clinical
      trials are discussed.

PMID- 20680097
TI  - Inhibition of mouse alkali burn induced-corneal neovascularization by recombinant
      adenovirus encoding human vasohibin-1.
AB  - PURPOSE: To evaluate the activity of recombinant adenovirus encoding human
      vasohibin-1 (Ad-Vasohibin-1) on mouse corneal neovasularization induced by alkali
      burn. METHODS: For the treatment group, 50 mice each received subconjunctival
      injection (5 microl) of 10(9) plaque forming units of replication-defective Ad
      Vasohibin-1. Control group mice received the same dosage of blank adenoviral
      vector (AdNull). Five days after injection, corneal neovascularization (CNV) was
      induced by placing 2.5 microl of 0.1 M NaOH on the right cornea for 30 s.
      Subsequently, CNV was observed and photographed every 3 days for a total duration
      of 9 days after the alkali burn. The percentage of neovascularized area was
      measured and compared with the AdNull control. The expression of human vasohibin
      1 protein was detected by immunohistochemistry and western blotting at 5, 8, and
      14 days after injection. The mRNA expression levels of murine vascular
      endothelial growth factor (Vegf), VEGF receptor 1 and 2 (Vegfr1, Vegfr2), and
      vasohibin-1 (Vash1) were analyzed and compared by real time quantitative reverse
      transcription polymerase chain reaction. RESULTS: The percentage of
      neovascularized area within the cornea was significantly reduced in mice treated
      with Ad-Vasohibin-1 compared to mice treated with AdNull at every time point
      after alkali-induced injury (7.11%+/-3.91% and 15.48%+/-1.79% of corneal area in
      the treatment and control groups, respectively, on day 3; 31.64%+/-4.71% and
      43.93%+/-6.15% on day 6, and 45.02%+/-9.98% and 66.24%+/-7.17% on day 9, all
      p<0.001). Human vasohibin-1 protein was detected at the injection sites on day 3
      after corneal burn and was highly expressed in the central subepithelial stroma
      and co-localized with neovascularized vessels within the alkali-treated cornea on
      day 6. On day 9, the peripheral cornea exhibited a similar staining pattern as
      the central cornea, but a more intense vasohibin-1 immunostaining signal was
      detected in the deep stroma. Some of the vasohibin-1 stain signal diffused into
      the frontal and deep stroma of the central cornea and was not co-localized with
      new vessels. By contrast, in mice injected with AdNull or normal corneas, no
      vasohibin-1 stain signal was detected within the corneas. Vasohibin-1 protein
      expression within treated corneas was also further confirmed by western blotting
      on day 5. Expression appeared to peak by day 8 and was maintained at high levels
      until day 14. However, Vasohibin-1 protein was not detected in the corneas of
      normal mice or mice treated with AdNull. Real-time quantitative reverse
      transcription polymerase chain reaction analysis showed that expression of Vegfr2
      and endogenous Vash1 mRNA were significantly decreased in the treatment versus
      control group (t(1)=-2.161, p(1)=0.047; t(2)=-2.236, p(2)=0.041). In contrast,
      there were no significant differences in Vegf and Vegfr1 mRNA expression levels
      between the treatment and control groups (p>0.05 for both). CONCLUSIONS:
      Subconjunctival injection of Ad-Vasohibin-1 significantly reduces corneal
      neovascularization in alkali-treated mouse corneas. This effect of anti
      neovascularization may be related to the downregulation of Vegfr2 expression.

PMID- 20680098
TI  - p62/sequestosome 1 as a regulator of proteasome inhibitor-induced autophagy in
      human retinal pigment epithelial cells.
AB  - PURPOSE: The pathogenesis of age-related macular degeneration involves impaired
      protein degradation in retinal pigment epithelial (RPE) cells. The ubiquitin
      proteasome pathway and the lysosomal pathway including autophagy are the major
      proteolytic systems in eukaryotic cells. Prior to proteolysis, heat shock
      proteins (HSPs) attempt to refold stress-induced misfolded proteins and thus
      prevent the accumulation of cytoplasmic protein aggregates. Recently,
      p62/sequestosome 1 (p62) has been shown to be a key player linking the
      proteasomal and lysosomal clearance systems. In the present study, the functional
      roles of p62 and HSP70 were evaluated in conjunction with proteasome inhibitor
      induced autophagy in human RPE cells (ARPE-19). METHODS: The p62, HSP70, and
      ubiquitin protein levels and localization were analyzed by western blotting and
      immunofluorescense. Confocal and transmission electron microscopy were used to
      detect cellular organelles and to evaluate the morphological changes. The p62 and
      HSP70 levels were modulated using RNA interference and overexpression techniques.
      Cell viability was measured by colorimetric assay. RESULTS: Proteasome inhibition
      evoked the accumulation of perinuclear aggregates that strongly colocalized with
      p62 and HSP70. The p62 perinuclear accumulation was time- and concentration
      dependent after MG-132 proteasome inhibitor loading. The silencing of p62, rather
      than Hsp70, evoked suppression of autophagy, when related to decreased LC3-II
      levels after bafilomycin treatment. In addition, the p62 silencing decreased the
      ubiquitination level of the perinuclear aggregates. Recently, we showed that
      hsp70 mRNA depletion increased cell death in ARPE-19 cells. Here, we demonstrate
      that p62 mRNA silencing has similar effects on cellular viability. CONCLUSIONS:
      Our findings open new avenues for understanding the mechanisms of proteolytic
      processes in retinal cells, and could be useful in the development of novel
      therapies targeting p62 and HSP70.

PMID- 20680099
TI  - Retinal ectopias and mechanically weakened basement membrane in a mouse model of
      muscle-eye-brain (MEB) disease congenital muscular dystrophy.
AB  - PURPOSE: Some forms of congenital muscular dystrophy are associated with cortical
      and retinal dysplasias. Protein O-mannose N-acetylglucosaminyltransferase 1
      (POMGnT1) knockout mice, one of the mouse models of muscular dystrophy, exhibit a
      thinner retina with reduced density of retinal ganglion cells. This study is
      aimed to further characterize the knockout retina, with special emphasis on the
      inner limiting membrane, the basement membrane of the retina. METHODS:
      Immunofluorescence staining and transmission electron microscopy were used to
      analyze the retinas. Atomic force microscopy was performed on the inner limiting
      membrane preparations to examine their mechanical properties. RESULTS: The inner
      limiting membrane of the knockout mice exhibited frequent breaks with protrusions
      of the Muller glial processes and ectopic placement of retinal ganglion cells
      into the vitreous humor. Disruptions in inner limiting membrane integrity
      developmentally precede the cellular abnormalities. Regions of disrupted inner
      limiting membrane were also associated with molecular abnormalities of Muller
      glia that included diminished presence of the integral membrane proteins Kir4.1
      (an inwardly rectifying potassium channel) and aquaporin-4. When measured with
      atomic force microscopy, the POMGnT1 knockout mouse inner limiting membrane (ILM)
      exhibited significantly reduced Young's modulus and is therefore mechanically
      weaker than the ILM from controls. CONCLUSIONS: Deficiency of POMGnT1-mediated
      glycosylation of dystroglycan is implicated in reduced stiffness of the ILM. The
      weakened ILM results in the disruption of the membrane and subsequent reduction
      in retinal integrity.

PMID- 20680100
TI  - TGFBI mutation screening and genotype-phenotype correlation in north Indian
      patients with corneal dystrophies.
AB  - PURPOSE: To screen a cohort of corneal dystrophy patients from North India for
      mutations in the transforming growth factor beta induced (TGFBI) gene, to
      correlate genotypes to phenotypes, to describe structural implications of various
      mutations on protein function, and to discuss the implications for diagnosis.
      METHODS: Eighty affected individuals from 61 unrelated families, who were
      diagnosed with autosomal dominant granular and/or lattice corneal dystrophy, were
      recruited for the study. Detailed clinical evaluation was undertaken for these
      patients to establish their corneal phenotypes. Genomic DNA was isolated from
      peripheral blood samples and all exons of TGFBI were screened for mutations by
      polymerase chain reaction (PCR) and direct DNA sequencing. Protein molecular
      dynamics (MD) simulations were performed for the mutations detected to assess the
      changes in protein structure. RESULTS: The most common mutations seen were
      Arg555Trp and Arg124Cys. Two novel mutations, Ser516Arg (c.DNA1548C>G), with a
      phenotype similar to granular corneal dystrophy I (GCDI), and Leu559Val
      (c.DNA1675T>G), with an atypical phenotype closely resembling epithelial basement
      membrane dystrophy/map dot fingerprint dystrophy, were identified. Protein
      modeling studies involving wild type and mutant protein indicated that the
      Leu559Val is a destabilizing mutation and that Ser516Arg could adversely affect
      the specific binding of Fas1 domain 4 with other proteins. In addition, two
      single-nucleotide polymorphisms, rs4669 and rs11331170, were also identified.
      Mutations were not identified in 8 affected individuals, 6 of whom were diagnosed
      with bowman layer dystrophy and 2 with lattice corneal dystrophy. CONCLUSIONS:
      This is the first comprehensive report of TGFBI mutations covering a large part
      of North India. Identification of novel mutations, the presence of phenotypic
      variability, and the genetic heterogeneity seen in our cases stress the need for
      mandatory screening of TGFBI for precise diagnosis and classification of corneal
      dystrophies.

PMID- 20680101
TI  - NGF and NGF-receptor expression of cultured immortalized human corneal
      endothelial cells.
AB  - PURPOSE: Several growth factors, including nerve growth factor (NGF) and vascular
      endothelial growth factor (VEGF), play an important role in the homeostasis of
      the ocular surface. The involvement of both these growth factors in the
      pathophysiology of intraocular tissues has been extensively investigated. Despite
      the expression of NGF receptors by corneal endothelium, to date the role of NGF
      on the endothelial cell remains to be determined. Using a clonal cell line of
      human corneal endothelial cells, the aim of this study was to investigate the
      expression of the NGF-receptor and the potential partnership of NGF and VEGF in
      maintaining cell viability in vitro. METHODS: A human endothelial cell line
      (B4G12), was cultured under serum-free conditions as previously described with
      and without addition of different concentrations of NGF, anti-NGF-antibody (ANA),
      or VEGF for 4 days and these cells were used for immuno-istochemical,
      biochemical, and molecular analyses. RESULTS: NGF induces overexpression of NGF
      receptors and synthesis and release of VEGF by endothelial cells and these cells
      are able to produce and secrete NGF. CONCLUSIONS: These observations indicate
      that human corneal endothelial cells are receptive to the action of NGF and that
      these cells may regulate NGF activity through autocrine/paracrine mechanisms.

PMID- 20680102
TI  - Aqueous humor neutrophil gelatinase-associated lipocalin levels in patients with
      idiopathic acute anterior uveitis.
AB  - PURPOSE: The purpose of this study was to evaluate the levels of neutrophil
      gelatinase-associated lipocalin (NGAL) in the aqueous humor in eyes with
      idiopathic acute anterior uveitis (AAU). METHODS: A comparative control study.
      Aqueous humor was collected from 20 eyes of 20 patients with idiopathic AAU. The
      control group included 20 aqueous samples from 20 patients about to undergo
      cataract surgery and without any other ocular or systemic diseases. The level of
      NGAL was determined with a commercially available ELISA kit. RESULTS: The
      concentration of NGAL in aqueous humor was markedly higher in patients with
      idiopathic AAU than in control subjects (Mann-Whitney U test, p<0.001). The level
      of NGAL was 139,197.38+/-183,426.36 (mean+/-SD) pg/ml in eyes with AAU and
      3,169.96+/-1,595.78 pg/ml in the eyes of the control group. CONCLUSIONS: The
      aqueous humor NGAL level is increased in eyes with idiopathic AAU. These results
      imply that NGAL is associated with the regulation of inflammation in patients
      with AAU and could be used as a biomarker of ocular inflammation and
      immunomodulatory treatment response.

PMID- 20680103
TI  - eCAM: Neuroendocrineimmune, Electroacupuncture and Gene Expression.

PMID- 20680104
TI  - Adverse events associated with anti-EGFR therapies for the treatment of
      metastatic colorectal cancer.
AB  - The epidermal growth factor receptor (EGFR), a member of the ErbB family of
      receptor tyrosine kinases, plays an important role in the control of cell growth
      and differentiation. Disruption of its signaling leads to neoplastic cell
      proliferation, migration, stromal invasion, resistance to apoptosis, and
      angiogenesis.EGFR is overexpressed in a variety of solid tumors, including
      colorectal cancer (CRC), and its overexpression is associated with poorer
      prognosis. One class of agents that is currently used to target EGFR in the
      treatment of metastatic CRC (mCRC) is the monoclonal antibodies. While the
      monoclonal antibody EGFR inhibitors lack many of the severe side effects commonly
      observed with cytotoxic chemotherapy, they are associated with a set of unique
      dermatological toxicities. This paper reviews the safety profile of the anti-EGFR
      monoclonal antibodies cetuximab and panitumumab in the treatment of mCRC.

PMID- 20680105
TI  - Efficacy of the monoclonal antibody EGFR inhibitors for the treatment of
      metastatic colorectal cancer.
AB  - Two anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (MoAbs)
      have been approved in Canada for the treatment of metastatic colorectal cancer
      (mCRC) - cetuximab, a mouse-human chimeric MoAb, and panitumumab, a fully human
      MoAb. This paper reviews the efficacy of the anti-EGFR monoclonal antibodies
      cetuximab and panitumumab - both as monotherapy and in combination with cytotoxic
      chemotherapy - in the treatment of mCRC. Both cetuximab and panitumumab have
      demonstrated clinical efficacy in monotherapy in patients with mCRC, an advantage
      that has recently been found to be limited largely to those with wild-type KRAS
      tumors. Advantages of using these agents in monotherapy include reduced cost and
      toxicity. While the addition of cetuximab to irinotecan has shown superior
      progression-free survival and response compared with cetuximab monotherapy, there
      is currently no evidence for a benefit of panitumumab in combination with
      irinotecan.

PMID- 20680106
TI  - KRAS mutation testing in the treatment of metastatic colorectal cancer with anti
      EGFR therapies.
AB  - Survival of patients with metastatic CRC (mCRC) has improved steadily over the
      past several decades, due largely to the development of new combinations of
      standard chemotherapy, as well as to the introduction of new targeted therapies.
      Among the available targeted therapies are two monoclonal antibodies that target
      the epidermal growth factor receptor (EGFR) - cetuximab and panitumumab - which
      have demonstrated efficacy in the treatment of mCRC. These therapies are
      associated with a unique set of toxicities and costs, prompting the need for
      tools to select patients who are most likely to derive a benefit from them.
      Mutations in the KRAS oncogene have consistently been shown to predict non
      response to cetuximab and panitumumab. The role of KRAS as a marker of efficacy
      of anti-EGFR therapies is reviewed.

PMID- 20680107
TI  - Junctional ectopic tachycardia.

PMID- 20680108
TI  - Septal accessory pathway: anatomy, causes for difficulty, and an approach to
      ablation.
AB  - Accessory pathway (AP) ablation is one of the most satisfying invasive
      electrophysiology procedures associated with high success rates and relatively
      few complications. Nevertheless, when APs are found on the cardiac septum,
      ablative procedures become complex, and unique pitfalls need to be avoided.These
      difficulties with septal ablation are magnified in the pediatric population. The
      relatively small heart, rapid nodal conduction, and proximity of the arterial
      system specifically complicate septal ablation in children. The
      electrophysiologist must use every tool in his or her armamentarium, including
      exact delineation of pathway location, identification of pathway potentials,
      detection of the presence of pathway slant, etc. In addition, an exact knowledge
      of the complex anatomy of the cardiac septum, including the posteroseptal space,
      the aortic cusp region, and the proximity of the AV conduction system and
      coronary vessels, becomes mandatory.In this review, we describe the developmental
      anatomy and regional anatomy of septal accessory pathways. We then discuss
      approaches to map specific to pathways in particularly problematic regions at or
      near the septum, including venous and aortic cusp related accessory pathways.

PMID- 20680109
TI  - Mitral annuloplasty using a cardiac resynchronization device.
AB  - Percutaneous Transvenous Mitral Annuloplasty for mitral regurgitation is in early
      stages of development and involves a complex intervention which can not be done
      in patients with left ventricular leads. Since functional mitral regurgitation is
      common in low ejection fraction states, we propose a device which can serve for
      annuloplasty in addition to cardiac resynchronization therapy and simplifying the
      intervention.

PMID- 20680110
TI  - Respirophasic Variations in the QRS Complex and Echocardiographic Equivalent in
      Pulmonary Embolism.
AB  - A respirophasic variation of the QRS complex was observed in a patient with
      bilateral pulmonary embolism and pulmonary hypertension. An analogous variation
      of the Sa systolic velocity of the tricuspid annular tissue Doppler imaging was
      also noticed. Both phaenomena persisted until the clinical and haemodynamic
      improvement of the patient. A mechanistic approach of the electric phaenomenon is
      proposed.

PMID- 20680111
TI  - Post-Operative Narrow Complex Tachycardia: What is the Mechanism?

PMID- 20680112
TI  - Regarding Article 'Multiple Episodes of Presyncope in a Pacemaker Dependent
      Patient: What is the Diagnosis?'.

PMID- 20680113
TI  - In Reply 'Multiple Episodes of Presyncope in a Pacemaker Dependent Patient: What
      is the Diagnosis?'.

PMID- 20680115
TI  - Conflict in least-developed countries: challenging the Millennium Development
      Goals.

PMID- 20680116
TI  - Women and tobacco: a fatal attraction.

PMID- 20680117
TI  - World laments loss of pathology service.

PMID- 20680118
TI  - Rough roads to better care.

PMID- 20680119
TI  - So many questions, so few answers. Interview by Les Olson.

PMID- 20680121
TI  - Pupil behaviour on school buses and potential risk factors for injury: an
      observational study.
AB  - OBJECTIVE: To observe pupil behaviour on school buses in Israel and identify
      hazards as a basis for improving school bus safety. METHODS: Data on student, bus
      driver and chaperone behaviours and on hazards associated with school buses, bus
      loading zones and bus stops were collected during an observational study
      conducted on school buses in rural communities in Israel. This report focuses on
      observations of student behaviour during school bus rides. Future reports will
      discuss the other findings. Student behaviours were assessed by means of chi(2)
      tests and logistic regression models. FINDINGS: Observations were made on 362
      rides on 125 buses on which 11 000 pupils travelled to and from school. Seatbelt
      use among the pupils was limited: on 23% of the rides all pupils fastened
      seatbelts, while on 42% none did. Seatbelt use was more frequent among primary
      school pupils than among older pupils. Pupil behaviours, such as rowdiness,
      noisiness, conflicts between pupils and not remaining seated were observed. These
      and other unsafe behaviours were more frequent on afternoon bus rides (odds
      ratio, OR: 3.2, 95% confidence interval, CI: 2.1-5.3), on routes with 5+ bus
      stops (OR: 4.1; 95% CI: 2.5-6.5) and on rides with primary school pupils (OR:
      1.8; 95% CI: 1.2-2.9). CONCLUSION: Without enforcement, government regulations
      and seatbelt availability on school buses are not enough to ensure seatbelt usage
      among pupils. Bus drivers cannot be expected to enforce seatbelt use and deal
      with pupil misconduct while also driving safely. Innovative strategies for
      improving pupil behaviour on school buses are needed to increase pupil safety.

PMID- 20680122
TI  - Infant and under-five mortality in Afghanistan: current estimates and
      limitations.
AB  - OBJECTIVE: To examine historical estimates of infant and under-five mortality in
      Afghanistan, provide estimates for rural areas from current population-based
      data, and discuss the methodological challenges that undermine data quality and
      hinder retrospective estimations of mortality. METHODS: Indirect methods of
      estimation were used to calculate infant and under-five mortality from a
      household survey conducted in 2006. Sex-specific differences in underreporting of
      births and deaths were examined and sensitivity analyses were conducted to assess
      the effect of underreporting on infant and under-five mortality. FINDINGS: For
      2004, rural unadjusted infant and under-five mortality rates were estimated to be
      129 and 191 deaths per 1000 live births, respectively, with some evidence
      indicating underreporting of female deaths. If adjustment for underreporting is
      made (i.e. by assuming 50% of the unreported girls are dead), mortality estimates
      go up to 140 and 209, respectively. CONCLUSION: Commonly used estimates of infant
      and under-five mortality in Afghanistan are outdated; they do not reflect changes
      that have occurred in the past 15 years or recent intensive investments in health
      services development, such as the implementation of the Basic Package of Health
      Services. The sociocultural aspects of mortality and their effect on the
      reporting of births and deaths in Afghanistan need to be investigated further.

PMID- 20680123
TI  - Disability after encephalitis: development and validation of a new outcome score.
AB  - OBJECTIVE: To develop a simple tool for assessing the severity of disability
      resulting from Japanese encephalitis and whether, as a result, a child is likely
      to be dependent. METHODS: A new outcome score based on a 15-item questionnaire
      was developed after a literature review, examination of current assessment tools,
      discussion with experts and a pilot study. The score was used to evaluate 100
      children in Malaysia (56 Japanese encephalitis patients, 2 patients with
      encephalitis of unknown etiology and 42 controls) and 95 in India (36 Japanese
      encephalitis patients, 41 patients with encephalitis of unknown etiology and 18
      controls). Inter- and intra-observer variability in the outcome score was
      determined and the score was compared with full clinical assessment. FINDINGS:
      There was good inter-observer agreement on using the new score to identify likely
      dependency (Kappa = 0.942 for Malaysian children; Kappa = 0.786 for Indian
      children) and good intra-observer agreement (Kappa = 1.000 and 0.902,
      respectively). In addition, agreement between the new score and clinical
      assessment was also good (Kappa = 0.906 and 0.762, respectively). The sensitivity
      and specificity of the new score for identifying children likely to be dependent
      were 100% and 98.4% in Malaysia and 100% and 93.8% in India. Positive and
      negative predictive values were 84.2% and 100% in Malaysia and 65.6% and 100% in
      India. CONCLUSION: The new tool for assessing disability in children after
      Japanese encephalitis was simple to use and scores correlated well with clinical
      assessment.

PMID- 20680125
TI  - Mortality and health among internally displaced persons in western Kenya
      following post-election violence, 2008: novel use of demographic surveillance.
AB  - OBJECTIVE: To evaluate mortality and morbidity among internally displaced persons
      (IDPs) who relocated in a demographic surveillance system (DSS) area in western
      Kenya following post-election violence. METHODS: In 2007, 204 000 individuals
      lived in the DSS area, where field workers visit households every 4 months to
      record migrations, births and deaths. We collected data on admissions among
      children < 5 years of age in the district hospital and developed special
      questionnaires to record information on IDPs. Mortality, migration and
      hospitalization rates among IDPs and regular DSS residents were compared, and
      verbal autopsies were performed for deaths. FINDINGS: Between December 2007 and
      May 2008, 16 428 IDPs migrated into the DSS, and over half of them stayed 6
      months or longer. In 2008, IDPs aged 15-49 years died at higher rates than
      regular residents of the DSS (relative risk, RR: 1.34; 95% confidence interval,
      CI: 1.004-1.80). A greater percentage of deaths from human immunodeficiency virus
      (HIV) infection occurred among IDPs aged > or = 5 years (53%) than among regular
      DSS residents (25-29%) (P < 0.001). Internally displaced children < 5 years of
      age did not die at higher rates than resident children but were hospitalized at
      higher rates (RR: 2.95; 95% CI: 2.44-3.58). CONCLUSION: HIV-infected internally
      displaced adults in conflict-ridden parts of Africa are at increased risk of HIV
      related death. Relief efforts should extend to IDPs who have relocated outside
      IDP camps, particularly if afflicted with HIV infection or other chronic
      conditions.

PMID- 20680124
TI  - Scale-up of a decentralized HIV treatment programme in rural KwaZulu-Natal, South
      Africa: does rapid expansion affect patient outcomes?
AB  - OBJECTIVE: To describe the scale-up of a decentralized HIV treatment programme
      delivered through the primary health care system in rural KwaZulu-Natal, South
      Africa, and to assess trends in baseline characteristics and outcomes in the
      study population. METHODS: The programme started delivery of antiretroviral
      therapy (ART) in October 2004. Information on all patients initiated on ART was
      captured in the programme database and follow-up status was updated monthly. All
      adult patients (> or = 16 years) who initiated ART between October 2004 and
      September 2008 were included and stratified into 6-month groups. Clinical and
      sociodemographic characteristics were compared between the groups. Retention in
      care, mortality, loss to follow-up and virological outcomes were assessed at 12
      months post-ART initiation. FINDINGS: A total of 5719 adults initiated on ART
      were included (67.9% female). Median baseline CD4+ lymphocyte count was 116
      cells/microl (interquartile range, IQR: 53-173). There was an increase in the
      proportion of women who initiated ART while pregnant but no change in other
      baseline characteristics over time. Overall retention in care at 12 months was
      84.0% (95% confidence interval, CI: 82.6-85.3); 10.9% died (95% CI: 9.8-12.0);
      3.7% were lost to follow-up (95% CI: 3.0-4.4). Mortality was highest in the first
      3 months after ART initiation: 30.1 deaths per 100 person-years (95% CI: 26.3
      34.5). At 12 months 23.0% had a detectable viral load (> 25 copies/ml) (95% CI:
      19.5-25.5). CONCLUSION: Outcomes were not affected by rapid expansion of this
      decentralized HIV treatment programme. The relatively high rates of detectable
      viral load highlight the need for further efforts to improve the quality of
      services.

PMID- 20680126
TI  - The effect of fiscal policy on diet, obesity and chronic disease: a systematic
      review.
AB  - OBJECTIVE: To assess the effect of food taxes and subsidies on diet, body weight
      and health through a systematic review of the literature. METHODS: We searched
      the English-language published and grey literature for empirical and modelling
      studies on the effects of monetary subsidies or taxes levied on specific food
      products on consumption habits, body weight and chronic conditions. Empirical
      studies were dealing with an actual tax, while modelling studies predicted
      outcomes based on a hypothetical tax or subsidy. FINDINGS: Twenty-four studies
      met the inclusion criteria: 13 were from the peer-reviewed literature and 11 were
      published on line. There were 8 empirical and 16 modelling studies. Nine studies
      assessed the impact of taxes on food consumption only, 5 on consumption and body
      weight, 4 on consumption and disease and 6 on body weight only. In general, taxes
      and subsidies influenced consumption in the desired direction, with larger taxes
      being associated with more significant changes in consumption, body weight and
      disease incidence. However, studies that focused on a single target food or
      nutrient may have overestimated the impact of taxes by failing to take into
      account shifts in consumption to other foods. The quality of the evidence was
      generally low. Almost all studies were conducted in high-income countries.
      CONCLUSION: Food taxes and subsidies have the potential to contribute to healthy
      consumption patterns at the population level. However, current evidence is
      generally of low quality and the empirical evaluation of existing taxes is a
      research priority, along with research into the effectiveness and differential
      impact of food taxes in developing countries.

PMID- 20680128
TI  - Validation of the shake test for detecting freeze damage to adsorbed vaccines.
AB  - OBJECTIVE: To determine the validity of the shake test for detecting freeze
      damage in aluminium-based, adsorbed, freeze-sensitive vaccines. METHODS: A double
      blind crossover design was used to compare the performance of the shake test
      conducted by trained health-care workers (HCWs) with that of phase contrast
      microscopy as a "gold standard". A total of 475 vials of 8 different types of
      World Health Organization prequalified freeze-sensitive vaccines from 10
      different manufacturers were used. Vaccines were kept at 5 degrees C. Selected
      numbers of vials from each type were then exposed to -25 degrees C and -2 degrees
      C for 24-hour periods. FINDINGS: There was complete concordance between HCWs and
      phase-contrast microscopy in identifying freeze-damaged vials and non-frozen
      samples. Non-frozen samples showed a fine-grain structure under phase contrast
      microscopy, but freeze-damaged samples showed large conglomerates of massed
      precipitates with amorphous, crystalline, solid and needle-like structures.
      Particles in the non-frozen samples measured from 1 microm (vaccines against
      diphtheria-tetanus-pertussis; Haemophilus influenzae type b; hepatitis B;
      diphtheria-tetanus-pertussis-hepatitis B) to 20 microm (diphtheria and tetanus
      vaccines, alone or in combination). By contrast, aggregates in the freeze-damaged
      samples measured up to 700 microm (diphtheria-tetanus-pertussis) and 350 microm
      on average. CONCLUSION: The shake test had 100% sensitivity, 100% specificity and
      100% positive predictive value in this study, which confirms its validity for
      detecting freeze damage to aluminium-based freeze-sensitive vaccines.

PMID- 20680127
TI  - Behavioural interventions for HIV positive prevention in developing countries: a
      systematic review and meta-analysis.
AB  - OBJECTIVE: To assess the evidence for a differential effect of positive
      prevention interventions among individuals infected and not infected with human
      immunodeficiency virus (HIV) in developing countries, and to assess the
      effectiveness of interventions targeted specifically at people living with HIV.
      METHODS: We conducted a systematic review and meta-analysis of papers on positive
      prevention behavioural interventions in developing countries published between
      January 1990 and December 2006. Standardized methods of searching and data
      abstraction were used. Pooled effect sizes were calculated using random effects
      models. FINDINGS: Nineteen studies met the inclusion criteria. In meta-analysis,
      behavioural interventions had a stronger impact on condom use among HIV-positive
      (HIV+) individuals (odds ratio, OR: 3.61; 95% confidence interval, CI: 2.61-4.99)
      than among HIV-negative individuals (OR: 1.32; 95% CI: 0.77-2.26). Interventions
      specifically targeting HIV+ individuals also showed a positive effect on condom
      use (OR: 7.84; 95% CI: 2.82-21.79), which was particularly strong among HIV
      serodiscordant couples (OR: 67.38; 95% CI: 36.17-125.52). Interventions included
      in this review were limited both in scope (most were HIV counselling and testing
      interventions) and in target populations (most were conducted among heterosexual
      adults or HIV-serodiscordant couples). CONCLUSION: Current evidence suggests that
      interventions targeting people living with HIV in developing countries increase
      condom use, especially among HIV-serodiscordant couples. Comprehensive positive
      prevention interventions targeting diverse populations and covering a range of
      intervention modalities are needed to keep HIV+ individuals physically and
      mentally healthy, prevent transmission of HIV infection and increase the agency
      and involvement of people living with HIV.

PMID- 20680129
TI  - Hospital capacity planning: from measuring stocks to modelling flows.
AB  - The metric of "bed numbers" is commonly used in hospital planning, but it fails
      to capture key aspects of how hospital services are delivered. Drawing on a study
      of innovative hospital projects in Europe, we argue that hospital capacity
      planning should not be based on beds, but rather on the ability to deliver
      processes. We propose using approaches that are based on manufacturing theory
      such as "lean thinking" that focuses on the value that different processes add
      for the primary customer, i.e. the patient. We argue that it is beneficial to
      look at the hospital, not from the perspective of beds or specialties, but rather
      from the path taken by the patients who are treated in them, the respective
      processes delivered by health professionals and the facilities appropriate to
      those processes. Systematized care pathways seem to offer one avenue for
      achieving these goals. However, they need to be underpinned by a better
      understanding of the flows of patients, work and goods within a hospital, the
      bottlenecks that occur, and translation of this understanding into new capacity
      planning tools.

PMID- 20680130
TI  - Building and retaining the neglected anaesthesia health workforce: is it crucial
      for health systems strengthening through primary health care?

PMID- 20680131
TI  - They also serve who stand and wait.....

PMID- 20680132
TI  - You can lead a horse to the water....

PMID- 20680133
TI  - Criminal behavior: A dispassionate look at parental disciplinary practices.

PMID- 20680134
TI  - Acute and transient psychosis: A paradigmatic approach.

PMID- 20680135
TI  - Schizophrenia is a disorder of aberrant neurodevelopment: A synthesis of evidence
      from clinical and structural, functional and neurochemical brain imaging studies.

PMID- 20680136
TI  - A 5-year course of predominantly obsessive vs. mixed subtypes of obsessive
      compulsive disorder.
AB  - BACKGROUND: Obsessive-compulsive disorder (OCD) is considered a heterogeneous
      disorder. One of the traditional approaches to subtype OCD is based on the
      predominance of obsessions, compulsions or both. Some studies suggest that the
      "predominantly obsessive" subtype of OCD may have poor outcome, whereas few other
      studies suggest that "mixed" OCD is associated with poor outcome. Therefore, it
      is not clear if the long-term course of "predominantly obsessive" subjects is
      different from those with "mixed" OCD. In the establishment of diagnostic
      validity of psychiatric conditions, differential course is an important
      validating factor. AIM: This study compares the 5-6 year course of the
      "predominantly obsessive" subtype with that of the "mixed" subtype of OCD with
      the objective of determining if the course of OCD differs according to subtypes
      and whether course could be a validating factor for subtyping OCD based on
      predominance of obsessions, compulsions or both. SETTING AND DESIGN: Tertiary
      hospital, institutional setting. The study has a retrospective cohort design.
      MATERIALS AND METHODS: Fifty-four subjects with "predominantly obsessions" and an
      equal number of the "mixed" subtype of OCD were recruited from the database of a
      specialty OCD clinic of a major psychiatric hospital. They were followed up after
      5-6 years. The Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) checklist and
      severity rating scale was used for assessing OCD. The course of OCD was
      determined according to predefined criteria. STATISTICS: The Chi-square/Fisher's
      exact test and the independent samples "t" test were used to compare categorical
      and continuous variables, respectively. Correlations were tested using the
      Pearson's correlation analysis. RESULTS: Thirty-eight "predominantly obsessive"
      (70%) and 39 "mixed" (72%) OCD subjects could be traced and evaluated. The course
      of illness was similar in the two subtypes. A majority of the sample (72%) did
      not have clinical OCD at follow-up. CONCLUSIONS: "Predominantly obsessive"
      subjects have a course similar to those with "mixed" OCD. Clinically, it is
      reassuring to know that obsessive subjects do not have an unfavorable course as
      was suggested by some previous studies. In this sample, course did not validate
      the subtyping method employed, but it would be premature to conclude that the
      subtyping method employed is incorrect based on the course alone. Prospective
      study of the course in larger samples and neurobiological and family-genetic data
      may help further validation.

PMID- 20680137
TI  - Cannabis-related psychosis: Presentation and effect of abstinence.
AB  - BACKGROUND: The correlation between cannabis and negative mental health outcomes
      has been unequivocally established. Nevertheless, there is still a great need to
      research different dimensions of cannabis-related disorders, among which the
      study of cannabis-related psychosis is very important. There is a dearth of
      research regarding phenomenology and effect of abstinence, particularly from
      India. This study attempts to research the clinical presentation of cannabis
      related psychosis and effect of abstinence. AIM: The aim of the present study was
      to document the clinical presentation of cannabis-related psychosis at
      presentation and after 7 days' abstinence from cannabis. MATERIALS AND METHODS:
      Subjects with psychosis following cannabis use without any other prior or
      concurrent psychiatric disorder presenting to the outpatient department of a
      large tertiary care hospital were consecutively recruited for study. They were
      observed in a drug-free, protected environment for 7 days, during which clinical
      features were recorded using the Brief Psychiatric Rating Scale (BPRS). RESULTS:
      Twenty male subjects were recruited and phenomenology was evaluated on the BPRS.
      Items with highest frequencies were unusual thought content (100%), excitement
      (75%), grandiosity (75%), hallucinatory behavior (70%) and uncooperativeness
      (65%). The least common symptoms were anxiety (5%), guilt feeling (5%),
      depressive mood (10%), motor retardation (10%) and blunted affect (30%). Nine
      subjects (45%) presented with cognitive dysfunction. Affective psychosis was the
      predominant diagnosis. At the end of 1 week of abstinence from cannabis, there
      was a significant decrease in scores. Significant improvement was observed in
      cognitive dysfunction, conceptual disorganization, grandiosity, tension,
      hostility, hallucinatory behavior and excitement. CONCLUSIONS: Cannabis-related
      psychosis presented with a predominantly affective psychosis and prominent
      thought disorder, excitement and violence. All subjects showed improvement in
      symptoms with abstinence from cannabis. A small heterogeneous sample and short
      duration of observation were the important limitations of this study.

PMID- 20680138
TI  - Pesticide poisoning in non-fatal deliberate self-harm: A public health issue:
      Study from Sundarban delta, India.
AB  - BACKGROUND: Non-fatal deliberate self-harm (DSH), particularly with pesticides,
      is a major public health problem in many developing countries of the world.
      Agriculture is the primary occupation of most people living in the Sundarban
      region in West Bengal, India. Pesticides are extensively used in agriculture, and
      these agents are most frequently used in DSH. AIM: This study aimed to identify
      the nature of methods and agents used in non-fatal DSH attempts in the Sundarban
      area under South 24 Parganas district of West Bengal. MATERIALS AND METHODS:
      Detailed demographic and clinical data on DSH cases of 13 Block Primary Health
      Centres' (BPHCs') admission registers were analyzed. One Focus Group Discussion
      (FGD) with the Panchayat Samiti of each block (totally 13 FDGs) was conducted to
      elicit the Samiti members' perception about the problem of pesticide-related DSH
      or suicide in the region. RESULTS: A total of 5,178 (1,887 male and 3,291 female)
      subjects were admitted at the BPHCs during the study period from 1999 to 2001.
      Organophosphorous pesticide poisoning was found to be the most common method
      (85.1%) in DSH. This emphasizes the importance of developing an urgent poisoning
      prevention program with a special focus on improving clinical services, as well
      as initiating farmers' education programs focusing on safe pesticide practices at
      the primary-care level.

PMID- 20680139
TI  - Repetitive love proposing: A case report and review of phenomenology of
      impulsivity and compulsivity.
AB  - Interest in opposite sex is a normal phenomenon; however, when this interest
      starts affecting one's own or others life in a pathological manner, it warrants
      clinical attention. We report the case of a young man who had a tendency to
      propose love to girls impulsively. Apart from the presence of this, otherwise,
      normal behavior in a pathological manner, another dimension of this case was that
      he was having obsessive-compulsive disorder too. Since both impulsivity and
      compulsivity are repetitive in nature and result in a sense of relief when the
      act is committed, the chance of impulsivity to be misconstrued as compulsivity is
      high. In light of important differences between compulsive and impulsive
      behavior, the psychopathology of the present case has been discussed.

PMID- 20680140
TI  - Clozapine: Current perspective.
AB  - The author conducted a review of studies that compared the efficacy, tolerability
      and indication for the use of clozapine in current perspectives for the treatment
      of resistant schizophrenia/ partial responders.

PMID- 20680142
TI  - Clinical practice guidelines for psychiatrists: Indian Psychiatric Society
      guidelines vs. international guidelines: A critical appraisal.
AB  - Various guidelines have been proposed to assist psychiatrists all over the world
      in making appropriate health-care decisions. Though the fundamental premises of
      all guidelines are the same, yet they differ in certain important aspects; this
      hampers the universality of these guidelines. There are many internationally
      accepted guidelines which are based on robust research; still they do not
      necessarily address the geographical and cultural differences. This necessitates
      the formulation of regional guidelines, which usually lack the background of
      robust regional research. The Indian Psychiatric Society (IPS) guidelines were
      also formulated to cater to the needs of the Indian population. It is now almost
      three years old, and it is high time it should be compared to the international
      guidelines, so as to appraise ourselves of the success or shortcomings of the
      guidelines. This article critically analyzes the IPS guidelines in comparison
      with the available international guidelines and schematically brings out the
      positive points, as well as the shortcomings, with the aim of further improvement
      in our indigenous guidelines.

PMID- 20680141
TI  - Proposal to the Indian Psychiatric Society for adopting a specialty section on
      addiction medicine (alcohol and other substance abuse).

PMID- 20680143
TI  - A case of neuroleptic malignant syndrome induced by olanzapine in postpartum
      period.
AB  - Neuroleptic malignant syndrome (NMS) is a life-threatening medical complication
      that occurs as a result of dopaminergic receptor blockage in nigrostriatal
      pathways. This syndrome is mainly accepted to be an idiosyncratic reaction for
      antipsychotic medications. Incidence of NMS induced by olanzapine - an atypical
      antipsychotic - is extremely rare. However, there has been contradiction on
      postpartum period as a risk factor for NMS. This case is of interest due to the
      fact that it happens on postpartum period and is induced by olanzapine. We aimed
      in this study to evaluate the successfully cured case of neuroleptic malignant
      syndrome induced by olanzapine in postpartum period with the literature view.

PMID- 20680144
TI  - Mania as an unique life event.
AB  - Despite substantial evidence of relationship between life events and psychiatric
      illness in general and mood disorder in specific, none of the research has
      documented 'mania' itself as a life event in the onset of mania in a family
      member who is genetically vulnerable to the disorder. We describe three such
      cases that had strong temporal association between manic episode in the family
      member and subsequent manic episodes among the first-degree relatives. Mania as a
      life event might play a significant role as a precipitator towards the onset of
      mood disorder with a special impact on those who have vulnerability towards the
      disorder; the cases are discussed from both psychological and biological
      perspective.

PMID- 20680146
TI  - Compulsive gambling in ancient Indian texts.

PMID- 20680145
TI  - A case presented with "as if" phenomenon.
AB  - A 22-year-old young male who was brought with a history of feeling of unreality,
      as if he himself and his surroundings had changed, since six months without any
      comorbid mental disorder or physical illness. Premorbidly he had some
      "obsessional traits". Mental state examination revealed perceptual disorder in
      the form of depersonalization and derealization with insight grade VI. The
      patient was admitted and treated with pharmacotherapy and behavior therapy
      (relaxation exercise).

PMID- 20680147
TI  - Rejoinder in reply to critical appraisal on "factitious schizophrenia".

PMID- 20680148
TI  - More on responsibility of psychiatrists in Indian setting.

PMID- 20680149
TI  - A rare case of head (scalp) trauma with foreign body.

PMID- 20680150
TI  - In vitro up-regulation of expression of GITR on human CD8+ cells.

PMID- 20680151
TI  - High risk of essential hypertension in males with intron 4 VNTR polymorphism of
      eNOS gene.
AB  - In this study 250 patients with essential hypertension were investigated in
      comparison to 218 normotensives for association with epidemiological parameters.
      Of these DNA samples from 176 patients and 168 controls were analyzed for intron
      4 27bp repeat polymorphism of eNOS gene. The study revealed significantly high
      risk of essential hypertension for individuals who were obese, with a positive
      family history and with non-vegetarian food habits. Though the intron 4b/a
      polymorphism of eNOS gene did not reveal any association with essential
      hypertension in general, males with a/a genotype of the polymorphism did show
      significantly high risk for developing hypertension.

PMID- 20680152
TI  - Linkage analysis of three families with arrythmogenic right ventricular
      cardiomyopathy in India.
AB  - BACKGROUND: Arrythmogenic Right Ventricular Cardiomyopathy (ARVC) is a primary
      myocardial disorder morphologically characterized by subtle to severe replacement
      of the right ventricular myocardium by fatty and fibrous tissue. ARVC is known to
      be highly prevalent in European population with recent reports implicating it to
      be a major cause of sudden death in young individuals even from American and
      Asian population. AIM: To implicate or exclude TMEM43 (ARVC-5), DSP(ARVC-8) genes
      and the yet to be identified gene at ARVC-6 locus in the pathogenesis in three
      families affected with ARVC from India. MATERIALS AND METHODS: Three families
      comprising of 42 affected/unaffected members were included in the study. Three
      microsatellite markers, D3S3613 (ARVC5) D10S1664 (ARVC6), D6S309 (ARVC8) were
      genotyped by PCR-based native PAGE. Two-point Linkage analysis was performed
      using LINKAGE program version 5.2 RESULTS AND DISCUSSION: LOD scores from linkage
      analysis for the microsatellite marker D10S1664 (ARVC-6) in families KS and REV
      have shown positive value hinting the involvement of this locus in the etiology
      of ARVC, while linkage analysis in the SB family ruled out involvement of DSP,
      TMEM43 and ARVC-6, as negative LOD scores were obtained with all three loci.
      Therefore, linkage analysis carried out in the present study indicates that ARVC
      6 (cumulative LOD score is equal to plus 1.203376 at theta is equal to 0.05)
      could be the locus harboring the mutated gene in two out of three families.

PMID- 20680153
TI  - MTHFR Gene variants C677T, A1298C and association with Down syndrome: A Case
      control study from South India.
AB  - BACKGROUND: The 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphisms
      and low folate levels are associated with inhibition of DNA methyltransferase and
      consequently DNA hypomethylation. The expanding spectrum of common conditions
      linked with MTHFR polymorphisms includes certain adverse birth outcome, pregnancy
      complications, cancers, adult cardiovascular diseases and psychiatric disorders,
      with several of these associations remaining still controversial. Trisomy 21 or
      Down syndrome (DS) is the most common genetic cause of mental retardation. It
      stems predominantly from the failure of chromosome 21 to segregate normally
      during meiosis. Despite substantial research, the molecular mechanisms underlying
      non-disjunction leading to trisomy 21 are poorly understood. MATERIALS AND
      METHODS: Two common variants C677T and A1298C of the MTHFR gene were screened in
      36 parents with DS children and 60 healthy couples from Tamil Nadu and Karnataka.
      The MTHFR genotypes were studied by RFLP analysis of PCR-amplified products and
      confirmed by sequencing. RESULTS: The CT genotype was seen in three each (8.3%)
      of case mothers and fathers. One case father showed TT genotype. All the control
      individuals exhibited the wild type CC genotype. A similar frequency for the
      uncommon allele C of the second polymorphism was recorded in case mothers (0.35)
      and fathers (0.37) in comparison with the control mothers (0.39) and fathers
      (0.37). CONCLUSION: This first report on MTHFR C677T and A1298C polymorphisms in
      trisomy 21 parents from south Indian population revealed that MTHFR 677CT
      polymorphism was associated with a risk for Down syndrome.

PMID- 20680154
TI  - Polymorphic analysis of MHClinked Heat Shock Protein 70 genes: Their
      susceptibility and prognostic implication in Kangri cancer cases of Kashmiri
      population.
AB  - Kangri cancer is a unique thermally-induced squamous cell carcinoma (SCC) of skin
      that develops due to persistent use of Kangri (a brazier), used by Kashmiri
      people, to combat the chilling cold during winter months. We designed a large
      scale case-control study to characterize the frequency of two polymorphisms
      within the MHC class III-linked HSP70genes, Hsp70-2 and Hsp70-hom, in order to
      find any association of these genotypic variants for predisposition to and
      clinical outcome of Kangri cancer patients from Kashmir valley in North India.
      Polymerase Chain Reaction and restriction enzymes were utilized to characterize
      the frequency of two polymorphisms with in Hsp70-2 and Hsp70-hom genes in 118
      Kangri carcinoma cases and 95 healthy controls from the same population of
      Kashmir. Association of high frequency allelic variants of Hsp70genes with
      various clinicopathological features of prognostic significance was assessed by
      Chi-square test using SPSS software. In this study, allelic frequency of Hsp70-2
      A/G heterozygote (0.87) (P = 0.012) was found to be significantly high in Kangri
      cancer cases compared to control (0.736) with a Relative Risk of 2.45 fold.
      Conversely, the allelic frequency of Hsp70-2 A/A allele in homozygous condition
      was significantly low in Kangri cancer cases and worked out to be 0.084 (Vs 0.252
      in control) with P is equal to 0.001, implicating it as a protective allele
      against Kangri cancer in subjects with this genotype. Similarly, significantly
      high frequency of 0.50 (Vs 0.29 in control) of Hsp70-homC/C allele was found in
      homozygous condition in Kangri cancer cases suggestive of a positive relative
      risk associated with this genotype (RR is equal to 2.47) (P is equal to 0.002).
      The overall allele frequency data analysis of Hsp70-2 and Hsp70-hom genes was
      significant (chi(2) is equal to 12.38, P is equal to 0.002; and chi(2) is equal
      to 12.21, P is equal to 0.002). The study also reveals considerable association
      of high frequency alleles of HSP70 genes, especially of Hsp70-2 A/G or G/G in
      Kangri tumors with clinico-pathological features of poor prognosis. These results
      indicate that the relative risk of Kangri cancer associated with Hsp70-2 and
      Hsp70- hom gene polymorphisms is confined to Hsp70-2 A/G or G/G and Hsp70homC/C
      haplotype in our population. The study, therefore, suggests Hsp70-2 A/G or G/G
      and Hsp70homC/C genotypes as potential susceptibility markers and independent
      prognostic indicators in Kangri carcinoma patients in Kashmiri population.

PMID- 20680155
TI  - Down's syndrome and cardiac tamponade with pulmonary tuberculosis in adults.
AB  - We describe a combination case of Down's syndrome and Cardiac Tamponade with
      Pulmonary Tuberculosis in an adult patient.

PMID- 20680156
TI  - Rare association of Turner syndrome with neurofibromatosis type 1 and tuberous
      sclerosis complex.
AB  - We report a rare association of Turner syndrome with both Neurofibromatosis type
      I and Tuberous Sclerosis. The patient had XOkaryotype with Turners stigmata and
      also had features of Neurofibromatosis 1 in the form of significant cafe-au-lait
      spots and Plexiform neurofibroma along with typical features of Tuberous
      Sclerosis complex. Pedigree analysis revealed that the elder brother of the
      proband in the family also suffered from Tuberous Sclerosis without the
      manifestation of Neurofibromatosis or any other genetic disorders. We hypothesize
      that these associations could be due to new independent mutations and also
      increased maternal and paternal age in a pre-disposition of Turner syndrome.

PMID- 20680157
TI  - Drugs impact on CYP-450 enzyme family: A pharmacogenetical study of response
      variation.
AB  - Pharmacogenetics is the study of genetic basis in the individual response to
      drugs. A thorough knowledge of this will lead to a future where tailor-made
      drugs, suiting an individual, can be used. Scandinavian countries have been known
      for wide usage of pharmacogenetics and the most widely used application is for
      genotyping CYP2D6 in treating psychiatric illness. The CYP-450 enzyme, a super
      family of microsomal drug-metabolizing enzymes, is the most important of enzymes
      that catalyzes phase-I drug metabolism reaction. CYP2D6 is a member of this
      family and it has been most intensively studied and the best example of
      pharmacogenetics variation in drug metabolism. Neuro-transmitter and drug acting
      CNS viz. codeine, dextromethorphan, metoprolol and tryptyline etc. are well
      metabolized by this enzyme. Thus, CYP2D6 is one of the most important and
      responsible enzymes which regulates bioavailability and metabolism of drug.
      Presently 75 alleles of CYP2D6 have been described which are responsible for
      variance of metabolism and toxicity of drugs. Thus, by determining variance of
      CYP2D6 using molecular approaches viz., PCR, real-time PCR, DNA micro-array and
      molecular docking can determine the adverse effects, drug toxicity,
      bioavailability and therapeutic potential of new drug.

PMID- 20680158
TI  - The role of capsaicin in spontaneous pacemaking activity in gastrointestinal
      tract.

PMID- 20680159
TI  - The hydrogen breath test: new uses for an old test.

PMID- 20680160
TI  - Electroacupuncture on visceral hyperalgesia - what is its mechanism?

PMID- 20680161
TI  - Achalasia - an update.
AB  - Achalasia is an esophageal motility disorder of unknown cause, characterized by
      aperistalsis of the esophageal body and impaired lower esophageal sphincter
      relaxation. Patients present at all ages, primarily with dysphagia for
      solids/liquids and bland regurgitation. The diagnosis is suggested by barium
      esophagram and confirmed by esophageal manometry. Achalasia cannot be cured.
      Instead, our goal is to relieve symptoms, improve esophageal emptying and prevent
      the development of megaesophagus. The most successful therapies are pneumatic
      dilation and surgical myotomy. The overall success rate of graded pneumatic
      dilation is 78%, with women and older patients responding best. Laparoscopic
      myotomy, usually combined with a partial fundoplication, has an overall success
      rate of 87%. Young patients, especially men, are the best candidates for surgical
      myotomy. Botulinum toxin injection into the lower esophageal sphincter and smooth
      muscle relaxants are usually reserved for older patients or those with co-morbid
      illness. The prognosis for achalasia patients to return to near normal swallowing
      is good, but the disease is rarely "cured" with a single procedure and
      intermittent touch-up procedures may be required.

PMID- 20680162
TI  - Gastroesophageal Reflux Disease and Helicobacter pylori: What May Be the
      Relationship?
AB  - Relationship between Helicobacter pylori (H. pylori) and gastroesophageal reflux
      disease (GERD) is controversial. We aimed to review the possible relationship
      between H. pylori infection and GERD. Epidemiological data indicate an inverse
      relationship between frequency of H. pylori infection and prevalence of GERD and
      its complications like Barrett's esophagus and esophageal adenocarcinoma. H.
      pylori eradication in patients with peptic ulcer disease may be associated with
      increased risk of development of GERD compared with untreated patients. Infection
      with cagA bearing strains of H. pylori was associated with less severe GERD
      including endoscopic esophagitis, possibly due to pangastritis leading to
      hypochlorhydria. Recent studies on inflammatory markers (IL-1beta and IL-1RN)
      suggest pro-inflammatory genotypes to be protective against development of severe
      GERD, especially in patients with H. pylori infection. Identification of
      candidate genes playing an important role in gastric acid secretion and visceral
      hypersensitivity to the esophageal epithelium might help in early detection of
      individuals susceptible to develop GERD. Interplay between H. pylori and host
      factors play an important role in the pathogenesis of GERD.

PMID- 20680163
TI  - Duodenal implications in the pathophysiology of functional dyspepsia.
AB  - Functional dyspepsia (FD) is a heterogeneous disorder associated with diverse
      pathophysiologic mechanisms. Studies have shown duodenal implications in the
      pathophysiology of FD. Duodenal hypersensitivity to acid, increased duodenal acid
      exposure, and abnormal responses to duodenal lipids or released cholecystokinin
      have been observed in patients with FD. Moreover, there is evidence indicating
      duodenal immune activation in FD. Alterations in the number of duodenal
      eosinophils or intraepithelial lymphocytes have been reported in a subset of FD
      patients, particularly in patients with post-infectious FD. Whether these
      abnormalities in the duodenum play a crucial role in the generation of dyspeptic
      symptoms needs to be elucidated. Further investigations on the relationship
      between duodenal abnormalities and well-known pathophysiologic mechanisms of FD
      are required. Furthermore, the causative factors related to the development of
      duodenal abnormalities in FD warrant further study.

PMID- 20680164
TI  - The role of weakly acidic reflux in proton pump inhibitor failure, has dust
      settled?
AB  - Patients that do not respond satisfactorily to standard proton pump inhibitor
      (PPI) treatment have become the most common presentation of gastro-esophageal
      reflux disease (GERD) in third referral gastrointestinal practices. The causes of
      refractory GERD include lack of compliance with treatment, residual acid reflux
      and weakly acidic reflux, esophageal hypersensitivity and persistent symptoms not
      associated with reflux. A role for weakly acidic reflux in symptom generation has
      been proposed since the availability of impedance-pH monitoring. The possible
      mechanisms by which persistent weakly acidic reflux might contribute to
      persistent symptoms in patients under PPI treatment may include esophageal
      distension by increased reflux volume, persistent impaired mucosal integrity (ie,
      dilation of intercellular spaces) and/or esophageal hypersensitivity to weakly
      acidic reflux events. To establish a definite role of weakly acidic reflux in
      refractory GERD, outcome studies targeting this type of reflux are still lacking.
      Treatment strategies to reduce the number or effect of weakly acidic reflux could
      involve drugs that decrease transient lower esophageal sphincter relaxations (ie,
      baclofen or similar), improve oesophageal mucosa resistance or visceral pain
      modulators. Finally, anti-reflux surgery can be considered, only if a clear
      symptom-weakly acidic reflux association was demonstrated.

PMID- 20680165
TI  - Capsaicin inhibits the spontaneous pacemaker activity in interstitial cells of
      cajal from the small intestine of mouse.
AB  - BACKGROUND/AIMS: Capsaicin (8-methyl-N-vanillyl-6-ninenamide), a compound found
      in hot peppers, has been reported to have different physiological actions on
      different cell types. Not much work has been done about the effect of capsaicin
      on the function of interstitial cells of Cajal (ICC). In the present study, we
      examined the action of external application of capsaicin on pacemaker activity in
      the cultured ICC from the small intestine of mouse. METHODS: We investigated the
      effect of capsaicin on pacemaker currents in cultured ICC from the small
      intestine of mouse using a whole cell patch-clamp technique and Ca(2+)-imaging
      analysis. RESULTS: When capsaicin was applied externally to the pacemaker
      generating ICC, it completely inhibited the pacemaker potential under current
      clamp mode (I = 0) and the pacemaker current under voltage-clamp mode at a -70 mV
      of holding potentials. The effect of capsaicin on pacemaker activity in ICC was
      shown dose dependently. The effect of capsaicin was not through the transient
      receptor potential of the vanilloid type 1 (TRPV1) channel as capsazepine did not
      block the effect of capsaicin. L-NAME, an inhibitor of nitric oxide synthase,
      also did not block the capsaicin-induced effects. When the action of capsaicin
      was examined in the intracellular calcium oscillation, it completely abolished
      the calcium oscillation. CONCLUSIONS: These results prove that the capsaicin has
      the inhibitory effects on the ICC which is carried out neither through TRPV
      channel nor the nitric oxide production. Intracellular Ca(2+) was also an
      important target for actions of capsaicin on ICC.

PMID- 20680166
TI  - Pathophysiological and psychosocial study in patients with functional vomiting.
AB  - BACKGROUND/AIMS: To explore clinical patterns, predisposing factors, psychosocial
      aspects and the possible pathogenesis in Functional Vomiting (FV) patients.
      METHODS: Ten healthy subjects and 19 FV patients participated in this study.
      Gastrointestinal symptoms and psychological state were evaluated by
      questionnaires, including Zung self-rating anxiety and depression scale and
      Eysenck personality questionnaire. Cutaneous electrogastrography, perfusion
      nutrition load test and intragastric pressure were performed in patients.
      Perfusion nutrition load test and intragastric pressure were also performed in
      healthy subjects. RESULTS: FV involved young female predominantly (4 male, 15
      female; age 25.8 +/- 8.4 years). Postprandial vomiting soon after meal without
      self-induced maneuver was the most common pattern of FV. Prevalence for overlaps
      between FV and functional dyspepsia was high (84.2%). Emotional changes and
      stress contributed to the development of FV. Prevalence of abnormal psychological
      status and personality in patients with FV was high (83.3% and 47.1%). Patients
      with FV had significant postprandial gastric dysrhythmia, impaired gastric
      accommodation and enhanced gastric sensitivity. There were significant
      correlations between clinical presentations, gastric function and psychological
      states. CONCLUSIONS: Patients with FV had abnormal psychological status, gastric
      dysmotility and hypersensitivity, which indicated that both of peripheral and
      central abnormalities could contribute to the pathogenesis of FV.

PMID- 20680167
TI  - The role of peripheral cannabinoid receptors type 1 in rats with visceral
      hypersensitivity induced by chronic restraint stress.
AB  - BACKGROUND/AIMS: This study was designed to investigate the possibility that the
      enhanced nociceptive responsiveness associated with canabonoid type 1 receptors
      (CB1Rs) and identify its role in mediating visceral hypersensitivity induced by
      chronic restraint stress. METHODS: Rats were exposed to daily partial restraint
      stress or sham partial restraint stress with intraperitoneal injection of the
      vehicle, CB1R agonist or antagonist for 4 consecutive days. We tested the
      visceromotor reflex to colorectal distention at day 0 and 5. Reverse
      transcription polymerase chain reaction and Western blot were used to assess the
      expression of CB1Rs. RESULTS: Intraperitoneal CB1 agonist (ACEA) injection
      significantly diminished (p < 0.05) the enhanced visceromotor reflex to
      colorectal distention at day 5 in stressed rats. Change in electromyogram
      response after ACEA over baseline, at pressure of 40 mmHg (+13.3 +/- 2.2), 60
      mmHg (+15.3 +/- 2.8) and 80 mmHg (+17.0 +/- 4.0) were much lower than in the
      control animals, which were +35.9 +/- 5.1, +41.1 +/- 6.3 and +54.1 +/- 9.6,
      respectively. Whereas, CB1 antagonist (SR141716A) had an opposite effect.
      Compared with control group, the change in electromyogram response after
      SR141716A over baseline was significantly enhanced (p < 0.05) for the distending
      pressure of 40 mmHg (+56.0 +/- 10.3), 60 mmHg (+74.6 +/- 12.3) and 80 mmHg (+82.9
      +/- 11.0), respectively. Reverse-transcription polymerase chain reaction and
      Western blotting demonstrated the stress-induced up-regulation of colon CB1Rs (p
      < 0.05). CONCLUSIONS: Our results suggest there is a key contribution of
      peripheral CB1Rs involved in the maintenance of visceral hyperalgesia after
      repeated restraint stress, providing a novel mechanism for development of
      peripheral visceral sensitization.

PMID- 20680168
TI  - Comparison of Direct Medical Care Costs Between Erosive Reflux Disease and Non
      erosive Reflux Disease in Korean Tertiary Medical Center.
AB  - BACKGROUND/AIMS: Gastroesophageal reflux disease is one of the most common and
      frequent chronic disease requiring considerable cost. We investigated the medical
      care costs in the erosive reflux disease (ERD) and non-erosive reflux disease
      (NERD). METHODS: The risk factors and the direct medical care costs were analyzed
      retrospectively in the ERD (178 patients) and NERD (183 patients) groups for a
      follow up period of 2 years. RESULTS: Logistic regression analysis showed that
      the ERD was more frequent in the groups of male gender, alcohol consumption,
      higher body mass index (>/=25 kg/m(2)), hiatal hernia, and higher triglyceride
      levels (>/=150 mg/dL). The direct medical care costs per person for 2 years were
      found to be $384.8 (ERD) and $412.9 (NERD) without statistically significant
      differences (p = 0.364). However, 9.3% (17/183) of the NERD patients had visited
      the emergency room compared to 3.4% (6/178) of the ERD patients (p = 0.029). In
      addition, more NERD patients were hospitalized than ERD patients (p = 0.006), and
      because of the longer hospitalization period, the medical costs in NERD patients
      were higher than ERD patients (p = 0.038). CONCLUSIONS: In spite of the different
      risk factors for ERD and NERD, total direct medical care costs were similar
      between the ERD and NERD group. However, more visits to emergency room and longer
      hospitalization period with more hospitalization costs in NERD patients account
      for the differences in medical service and usage distribution between the 2
      groups.

PMID- 20680169
TI  - Patients with irritable bowel syndrome exhale more hydrogen than healthy subjects
      in fasting state.
AB  - BACKGROUND/AIMS: Irritable bowel syndrome (IBS) is a common disorder with
      significant morbidity and impairment of quality of life. Most patients (26%-83%)
      with IBS from Asia reported bloating. Bloating may result from increased amount
      or distribution of gas in the gut or exaggerated perception of distension. To
      evaluate whether patients with IBS produce more hydrogen even in fasting state,
      we conducted a study with the following aims: (1) to estimate fasting breath
      hydrogen levels among patients with IBS as compared with healthy controls (HC)
      and (2) to study relationship between symptoms of IBS and stool frequency and
      fasting breath hydrogen levels. METHODS: Eighty-one patients with IBS (Rome III
      criteria) and 123 HC were included. Hydrogen breath test was performed using a
      gas analyzer after an overnight (12 hours) fast. Both patients with IBS and HC
      had similar preparation before breath hydrogen estimation. RESULTS: Of 93
      patients with symptoms of functional gastrointestinal disorders, 81 (87.1%) met
      Rome III criteria and 12 (12.9%) were negative and hence, excluded from the
      study. Patients with IBS were comparable in age (35 +/- 11.8 years vs 37.5 +/-
      13.1 years, p = NS) and gender (male 61/81 [75.3%] vs 77/123 [62.6%], p=0.67)
      with HC. Average fasting breath hydrogen was higher in patients with IBS as
      compared to HC (mean 10.1 +/- 6.5 ppm vs 5.5 +/- 6.2 ppm, p < 0.0001). Number of
      stools per week correlated with average fasting breath hydrogen excretion in
      patients with IBS (r = 0.26, p = 0.02). CONCLUSIONS: Inspite of similar
      preparation for the test, fasting breath hydrogen was higher in patients with IBS
      as compared to HC. Number of stools per week correlated with fasting breath
      hydrogen levels among patients with IBS.

PMID- 20680170
TI  - Effect of electroacupuncture on visceral hyperalgesia, serotonin and fos
      expression in an animal model of irritable bowel syndrome.
AB  - BACKGROUND/AIMS: While it is well established that acupuncture relieves somatic
      pain, its therapeutic effect on visceral pain such as irritable bowel syndrome
      (IBS) is unclear. We evaluated the effect of acupuncture in treating visceral
      hyperalgesia in an animal model. METHODS: Sprague-Dawley rats (n = 8 per group)
      with prior neonatal maternal separation stress were randomly allocated to receive
      3-day treatment of either electroacupuncture (EA) or sham acupuncture at acupoint
      ST-36. Another group of rats without prior maternal separation was included as
      non-handled controls. Colorectal distension was performed on the day after
      acupuncture treatment. The 3 groups were compared for pain threshold as
      determined by abdominal withdrawal reflex and visceromotor response as measured
      by electromyogram. Colon, spinal cord, and brainstem were sampled for topographic
      distribution and quantitative assessment of serotonin and Fos expression by
      immunohistochemistry. RESULTS: Rats in EA group had significantly higher pain
      threshold compared to those in sham acpuncture group (25.0 +/- 5.7 mmHg vs 18.7
      +/- 5.2 mmHg, p = 0.01) and it was comparable with that of non-handled treatment
      naive controls (29.4 +/- 9.3 mmHg, p = 0.28). They also had lower visceromotor
      response as measured by electromyogram compared to those received sham
      acupuncture at all colorectal distension pressures. EA significantly suppressed
      Fos expression in doral raphe nuclei of brainstem, superficial dorsal horn of
      spinal cord and colonic epithelium but suppressed 5-HT expression only in
      brainstem and spinal cord. CONCLUSIONS: Electro acupuncture attenuates visceral
      hyperlagesia through down-regulation of central serotonergic activities in the
      brain-gut axis.

PMID- 20680171
TI  - A case of eosinophilic esophagitis with food hypersensitivity.
AB  - Eosinophilic esophagitis (EoE) is a disorder characterized by isolated
      eosinophilic infiltration of the esophagus with esophageal symptoms. Although
      some patients with EoE are related to food hypersensitivity, it is hard to
      identify causative foods. This report describes a case of EoE with dysphagia. A
      28-year-old man presented with dysphagia and substernal discomfort for 15 days.
      He had taken a protein complex for 2 months. Endoscopy showed several linear
      furrows and multiple mucosal nodularities on the lower and mid esophagus, and the
      biopsies of esophagus revealed marked eosinophil infiltration in the mucosa. The
      skin testing for the protein complex was positive. The patient was successfully
      treated with withholding treatment.

PMID- 20680172
TI  - A case of amyotrophic lateral sclerosis presented as oropharyngeal Dysphagia.
AB  - Amyotrophic lateral sclerosis is a rare disease. It is a fatal neurodegenerative
      disease characterized by progressive muscular paralysis reflecting degeneration
      of motor neurons which leads to muscle weakness and muscle wasting. Respiratory
      failure limits survival to 2-5 years after disease onset. Several clinical
      manifestations including dysphagia can result in reductions in both the quality
      of life and life expectancy. Dysphagia occurs at onset in about one third of
      case, although generally it occurs in later stage of the disease. Evaluation of
      dysphagia includes video-fluoroscopic swallow study, radiological esophagogram,
      flexible endoscopic examination, ultrasound examination, conventional manometry
      and electromyography. We report a case of amyotrophic lateral sclerosis in a 54
      year-old man presenting oropharyngeal dysphagia which was diagnosed by high
      resolution esophageal manometry presenting abnormality of the upper esophageal
      sphincter.

PMID- 20680173
TI  - Aggravation of Dysphagia aortica after wearing the abdominal binder.
AB  - Dysphagia aortica is a rare etiology of dysphagia resulting from extrinsic
      compression of esophagus by thoracic aortic aneurysm or tortuosity and elongation
      of thoracic aorta. The clinical findings resemble those of esophageal malignancy
      or esophageal motility disorders. Therefore, primary diagnosis of dysphagia
      aortica is very difficult. We, herein, report a case of dysphagia aortica
      aggravated by wearing the abdominal binder in a 70-year-old woman and review the
      literature pertaining to this condition. Dysphagia aortica should be considered
      in the differential diagnosis of dysphagia.

PMID- 20680174
TI  - How to Interpret Esophageal Impedance pH Monitoring.
AB  - Esophageal impedance pH monitoring provides quantitative data on esophageal acid
      exposure and has the ability to correlate the symptoms with acid exposure events.
      The nomenclature for the reflux patterns detected in impedance pH monitoring as
      well as the normal values have been determined. Data interpretation is similar to
      24-hour pH monitoring, ie, searching for an increase in the number of reflux
      episodes, prolonged acid or volume exposure or increased numbers of proximal
      reflux events. In particular, the key clinical measurements for impedance testing
      on proton pump inhibitor therapy are the number of acid and non-acid reflux
      episodes and their relationship with the symptoms using the symptom index or
      symptom-association probability.

PMID- 20680175
TI  - A 74-year-old woman with Dysphagia: what is your diagnosis by endoscopic and
      barium swallow finding?

PMID- 20680176
TI  - A 59-year-old female presenting with bloating and flatulence: is the intestinal
      gas volume in plain abdominal radiographs correlated with symptoms?

PMID- 20680177
TI  - Is there any association of osteoporosis with proton pump inhibitor use?
      (Gastroenterology 2010;138:896-904).

PMID- 20680178
TI  - Long-term Prognosis of Postinfectious Irritable Bowel Syndrome (Gut 2010;59:605
      611).

PMID- 20680179
TI  - A Validated Tool for Psychiatric Comorbidity in the Patients With Functional
      Dyspepsia: Author's Reply.

PMID- 20680180
TI  - Rice and spicy diet.

PMID- 20680181
TI  - Rice and Spicy Diet: Author's Reply.

PMID- 20680182
TI  - Is Rome III Criteria for Irritable Bowel Syndrome More Useful Than Rome II
      Criteria in Korea?

PMID- 20680183
TI  - Is Rome III Criteria for Irritable Bowel Syndrome More Useful Than Rome II
      Criteria in Korea?: Author's Reply.

PMID- 20680184
TI  - Noncardiac chest pain in young patients.

PMID- 20680185
TI  - Noncardiac Chest Pain in Young Patients: Author's Reply.

PMID- 20680186
TI  - Erratum: "A complete set of material properties of single domain
      0.26Pb(In(12)Nb(12))O(3)-0.46Pb(Mg(13)Nb(23))O(3)-0.28PbTiO(3) single crystals"
      [Appl. Phys. Lett. 96, 012907 (2010)].
AB  - [This corrects the article on p. 012907 in vol. 96.].

PMID- 20680187
TI  - Extrapyramidal symptoms associated with antidepressants--a review of the
      literature and an analysis of spontaneous reports.
AB  - BACKGROUND: Antidepressant-induced extrapyramidal symptoms (EPS) represent an
      underrecognized but important clinical entity. We reviewed the literature on new
      antidepressants and conducted an analysis of cases from the FDA Adverse Event
      Reporting System (AERS), which has not been published before. METHODS: A
      literature review was conducted using PubMed, Ovid, MEDLINE, PsycINFO, and the
      Cochrane Database. Search terms used were extrapyramidal, antidepressants,
      selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants
      (TCAs), serotonin-norepinephrine reuptake inhibitors (SNRIs), norepinephrine
      dopamine reuptake inhibitors (NDRIs), miscellaneous antidepressants, and
      monoamine oxidase inhibitors (MAOIs). Inclusion criteria for the FDA AERS
      analysis were cases of EPS reported by physicians, cases where patients were on
      one antidepressant, and cases reported between July 2005 and March 2008. Reports
      of patients who were on concurrent psychotropics were excluded. RESULTS: Our
      literature review revealed 1 report each of EPS for duloxetine, nefazodone, and
      bupropion, 3 for escitalopram, and 4 for citalopram. For the FDA AERS analysis,
      89 cases met our inclusion criteria: duloxetine was implicated in 66% of cases,
      sertraline in 10%, escitalopram in 7%, and bupropion in 6%. CONCLUSIONS: EPS have
      been reported with different classes of antidepressants, are not dose related,
      and can develop with short-term or long-term use. In view of the risk for
      significant morbidity and decreased quality of life, clinicians must be aware of
      the potential for any class of antidepressants to cause these adverse effects.

PMID- 20680188
TI  - Neuroticism but not omega-3 fatty acid levels correlate with early responsiveness
      to escitalopram.
AB  - BACKGROUND: Omega-3 fatty acid (O3FA) levels and dimensional personality measures
      have been associated with major depression and the course of depressive illness.
      We sought to study the utility of O3FA levels and dimensional personality
      measures as predictors of early improvement with escitalopram. METHODS: Twenty
      four participants were enrolled in an open-label trial of escitalopram 10 mg/d
      for 4 weeks. Baseline erythrocyte O3 levels and dimensional personality
      assessments were obtained. RESULTS: Using a conservative, intention-to-treat
      analysis, baseline neuroticism (r = -0.57; P = .007), as measured by the Revised
      NEO Personality Inventory but not erythrocyte O3 levels, was correlated with
      improvements on escitalopram. A facet analysis of the neuroticism domain showed
      the relationship with antidepressant response to be focused on trait anxiety (r =
      -0.65; P = .002). CONCLUSIONS: Anxiety may have important prognostic implications
      on subsequent response to selective serotonin reuptake inhibitors, such as
      escitalopram.

PMID- 20680189
TI  - Early improvements in anxiety, depression, and anger/hostility symptoms and
      response to antidepressant treatment.
AB  - BACKGROUND: The purpose of this study was to examine whether treatment response
      to fluoxetine by depressed outpatients was predicted by early improvement on any
      of 3 subscales (Anxiety, Depression, and Anger/Hostility) of the Symptom
      Questionnaire (SQ). METHODS: We evaluated 169 depressed outpatients (52.6%
      female) between ages 18 and 65 (mean age, 40.3 +/- 10.6 years) meeting DSM-IIIR
      criteria for major depressive disorder (MDD). All patients completed the SQ at
      baseline (week 0) and at weeks 2, 4, and 8 of treatment with fluoxetine 20 mg/d.
      We defined treatment response as a > or= 50% reduction in score on the 17-item
      Hamilton Rating Scale for Depression, and early improvement on 3 SQ subscales
      (Anxiety, Depression, and Anger/Hostility) as a >30% reduction in score by week
      2. RESULTS: The percentage of patients with significant early improvement in
      anger was significantly greater than the percentage of those with early
      improvements in anxiety or depression. When early improvement on the Anxiety,
      Depression, and Anger/Hostility subscales of the SQ were assessed independently
      by logistic regression, all 3 subscales were predictors of response to treatment.
      CONCLUSIONS: Early improvement in anger, anxiety, and depressive symptoms may
      predict response to antidepressant treatment among outpatients with MDD.

PMID- 20680190
TI  - The relationship of marital status and clinical characteristics in middle-aged
      and older patients with schizophrenia and depressive symptoms.
AB  - BACKGROUND: This study examines the relationship of marital status to depression,
      positive and negative symptoms, quality of life, and suicidal ideation among 211
      patients with schizophrenia-spectrum disorders and subsyndromal depressive
      symptoms. We hypothesized that single participants would have more severe
      symptomatology than married and cohabitating participants. METHODS: Outpatients,
      age 40 or older, were diagnosed with schizophrenia or schizoaffective disorders
      using the MINI Structured Clinical Interview for DSM-IV Axis 1 Disorders.
      Participants exhibited a score of >8 on the Hamilton Rating Scale for Depression
      but did not meet criteria for a major depressive episode. RESULTS: Participants
      who were married or cohabitating had a later age of onset of first psychotic
      episode or hospitalization than those who were single (age, 29.35 vs 24.21).
      Married participants rated their quality of life higher than those who were
      single (mean Quality of Life Scale scores, 72.28 vs 53.87) and had less suicidal
      ideation than those who were divorced, widowed, or separated (7.4% vs 29.2%).
      CONCLUSIONS: In middle-aged and older individuals with schizophrenia or
      schizoaffective disorder and depressive symptoms, marriage appeared to enhance
      quality of life and protect against suicidal ideation. Efforts that focus on
      providing additional support for those who are experiencing divorce or separation
      could prove to be lifesaving for these individuals.

PMID- 20680191
TI  - Unrecognized physical illness prompting psychiatric admission.
AB  - BACKGROUND: We assessed factors that might contribute to clinicians erroneously
      attributing medically based changes in a patient's mental status to psychiatric
      illness. METHODS: Records of 1340 patients admitted to a VA hospital psychiatric
      unit and 613 to a public hospital psychiatric unit from 2001 to 2007 were
      reviewed. Cases admitted because of an unrecognized medical disorder underwent
      further analysis of the preadmission assessment and documented history of mental
      illness. RESULTS: Of 1340 patients whose records were reviewed, 55 (2.8%) had a
      medical disorder that caused their symptoms. Compared with patients admitted to
      medical units, patients inappropriately admitted to psychiatric units had lower
      rates of completion of medical histories, physical examinations, cognitive
      assessments, indicated laboratory and/or radiologic studies, and treatment of
      abnormal vital signs (P < .001 in each case). Among patients admitted to
      psychiatric units, 85.5% had a history of mental illness vs 30.9% of comparable
      admissions to medical units (Chi2(1) = 35.85; P < .001). CONCLUSIONS: Key
      assessment procedures are less likely to be performed in patients with mental
      status changes who are admitted to psychiatric units than in comparable patients
      admitted to medical units. Symptoms of patients with a history of mental illness
      are more likely to be attributed to psychiatric illness than are those of
      patients without such a history.

PMID- 20680192
TI  - Biological correlates of direct exposure to terrorism several years postdisaster.
AB  - BACKGROUND: It is important to understand long-term biological and psychiatric
      correlates of intense exposure to terrorism. METHODS: We assessed psychiatric
      diagnoses and biological stress measures in 50 healthy, highly exposed Oklahoma
      City bombing survivors recruited from a bombing registry 6 1/2 to 7 years
      postdisaster, comparing them with demographically matched, nonexposed community
      members. The Diagnostic Interview Schedule (DIS) determined Axis I psychiatric
      diagnoses. Participants' salivary cortisol levels were obtained at 8 am, and
      physiologic assessment measured participants' heart rate and blood pressure
      responses to a bombing-related interview. RESULTS: Eleven survivors with
      posttraumatic stress disorder (PTSD) had significantly higher cortisol levels
      than did both non-PTSD survivors and controls. Survivors with and without PTSD
      did not differ in any autonomic reactivity measure, whereas the total survivor
      group had significantly higher reactivity than controls in all measures. Positive
      correlations occurred between several autonomic reactivity measures, but none
      between cortisol and autonomic measures. CONCLUSIONS: Results differentiate the
      autonomic and cortisol systems relative to terrorism exposure. Findings support
      research associating PTSD with hypothalamic-pituitary-adrenal (HPA) axis changes,
      whereas autonomic reactivity appeared to be a more generalized trauma response.
      Correlation statistics substantiated a lack of connection between the 2
      biological systems. Follow-up could elucidate the long-term course of these
      stress systems and eventual health status in survivors, in view of the medical
      morbidity noted in PTSD studies.

PMID- 20680193
TI  - OROS methylphenidate in the treatment of adults with ADHD: a 6-month, open-label,
      follow-up study.
AB  - BACKGROUND: This open-label trial followed a previously reported randomized,
      placebo-controlled trial of osmotic release oral system (OROS) methylphenidate
      (MPH) for the treatment of personality disorder (PD). Important findings from the
      double-blind phase are reexamined for long-term significance. METHODS: Of 41
      patients who completed the double-blind, placebo-controlled trial, 34 continued
      into this open-label phase. The Wender-Reimherr Adult Attention Deficit Disorder
      Scale (WRAADDS) measured outcome. Patients were categorized using previously
      defined attention-deficit/hyperactivity disorder (ADHD) groups: ADHD alone, ADHD
      with emotional dysregulation (ADHD + ED), and ADHD plus emotional dysregulation
      plus oppositional symptoms (ADHD + ED + ODD); and 3 post hoc personality
      categories: patients with no PD (PD-negative), patients with 1 PD (PD-positive),
      and patients meeting criteria for 2 or more PDs (PD-plus). RESULTS: Three WRAADDS
      defined ADHD dimensions improved at similar levels (attention + disorganization,
      61%; hyperactivity + impulsivity, 60%; and emotional dysregulation, 66%). All
      ADHD subgroups (ADHD alone, ADHD + ED, and ADHD + ED + ODD) improved. ADHD + ED +
      ODD patients had the highest level of social maladjustment at baseline and showed
      the most long-term improvement in this area. PD-plus patients were less likely to
      complete the study or show improvement. Sixty-five percent of treatment
      responders were on moderate doses (< or =54 mg/d) of OROS MPH. Vital signs and
      ECGs did not differ from baseline. CONCLUSIONS: Eighteen (44%) patients completed
      the trial. All 3 ADHD dimensions showed similar, well-maintained improvement.
      Patients with several PDs responded poorly to treatment in this small trial.

PMID- 20680194
TI  - Leukocytosis after lithium and clozapine combination therapy.

PMID- 20680195
TI  - A series of lanthanide-organic polymers incorporating nitrogen-heterocyclic and
      aliphatic carboxylate mixed-ligands: structures, luminescent and magnetic
      properties.
AB  - Seven new lanthanide-organic coordination polymers incorporating both nitrogen
      heterocyclic dicarboxylate and various auxiliary ligands,
      {[Ln(3)(Hpimda)(4)(mu(2)-HCOO).5H(2)O].H(2)O}(n)} Ln = Sm (1), Ln = Eu (2), Ln =
      Gd (3), Ln = Dy (4), Ln = Ho (5), {[Ce(2)(Hpimda)(2)(mu(4)
      C(2)O(4)).8H(2)O].2H(2)O}(n) (6), {[Yb(2)(pyda)(mu(4)
      C(2)O(4))(2).4H(2)O].3H(2)O}(n) (7) (H(3)pimda = 1H-2-propyl-4,5
      imidazoledicarboxylic acid, H(2)pyda = 2,6-pyridinedicarboxylic acid) have been
      fabricated successfully and characterized systematically. Complexes 1-5 are
      isomorphous and isostructural, and are built from two-dimensional (2-D) double
      decker networks based on the tetranuclear basic carboxylate as a secondary
      building unit (SBU). Both polymers 6 and 7 feature a (3,4)-connected 3-D
      framework consisting of 2-D lanthanide-organic hexagonal grids, which are further
      interlinked via the mu(4)-oxalate ligand. The results of magnetic determination
      show the same end-to-end bridging fashion of formate group results in different
      magnetic properties occurring between lanthanide centers. The luminescence
      emission spectra of the complexes vary depending on the lanthanide ion present.

PMID- 20680196
TI  - High-yield exfoliation of three-dimensional graphite into two-dimensional
      graphene-like sheets.
AB  - Edge-functionalized graphite (EFG) is prepared via a "direct" covalent attachment
      of organic molecular wedges. The EFG is dispersed in N-methyl-2-pyrrolidone with
      a concentration as high as 0.27 mg mL(-1), leading to high-yield exfoliation of
      the three-dimensional graphite into two-dimensional graphene-like sheets.

PMID- 20680197
TI  - Hierarchical structures in AB/AC type diblock-copolymer blend particles.
AB  - This paper describes the first preparation of diblock-copolymer blend particles
      with hierarchical inner structures. AB/AC type diblock-copolymer blend particles
      were successfully prepared by a simple solvent evaporation method. The inner
      phase separation structures can be controlled by changing the molecular weight
      combinations of common polymer segments. Furthermore, the one-to-one blend of two
      diblock-copolymers formed Janus particles with two different domains of
      microphase separation. Pd ions were successfully introduced into the particles
      with the onion-like structure. These organic-inorganic composite particles can be
      used as a novel class of nanomaterials applicable to photonics and electronics.

PMID- 20680198
TI  - Proton transport in choline dihydrogen phosphate/H(3)PO(4) mixtures.
AB  - Mixtures of the plastic crystal material choline dihydrogen phosphate
      [Choline][DHP] and phosphoric acid, from 4.5 mol% to 18 mol% H(3)PO(4), were
      investigated and shown to have significantly higher proton conductivity compared
      to the pure [Choline][DHP]. This was particularly evident from the
      electrochemical hydrogen reduction reaction and the proton NMR diffusion
      measurements, in addition to ionic conductivity measured from the impedance
      spectroscopy. The ionic conductivity was observed to increase by more than an
      order of magnitude in phase I (i.e. the highest temperature solid phase in
      [Choline][DHP]) reaching up to 10(-2) S cm(-1). The multinuclear NMR spectroscopy
      data suggest that, at least on the timescale of the NMR measurement, the H(+)
      cations and [DHP] anions are equivalent in both phases. The pulsed field gradient
      NMR diffusion measurements of the 18 mol% acid sample indicate that all three
      ions are mobile, however the H(+) diffusion coefficient is an order of magnitude
      higher than for the [Choline] cation or the [DHP] anion, and therefore conduction
      in these materials is dominated by proton conductivity. The thermal stability, as
      measured by TGA, is unaffected with increasing acid additions and remains high;
      i.e. no significant mass loss below 200  degrees C.

PMID- 20680199
TI  - Designing molecular materials and strategies for the electrochemical detection of
      nitric oxide, superoxide and peroxynitrite in biological systems.
AB  - We present an overview of the successes and challenges still faced in the
      detection of NO, O(2)(*-) and ONOO(-) in biological media. We provide a full
      discussion on the electrochemical analyses of each of these species and we
      summarise the significant research contributions towards the development of
      sensors for individual and simultaneous detection of these species. We emphasize
      the importance of understanding the potential interferents in developing such
      sensors. We show that significant advances have been made with regard to the
      detection of NO in biological media leading to the development of marketable NO
      sensors, though there is room for improvement in terms of interferences. A brief
      outlook into the future perspectives of the use of a multi-electrochemical array
      sensor for simultaneous detection of NO, O(2)(*-) and ONOO(-) is presented.

PMID- 20680200
TI  - Sorbents for CO(2) capture from flue gas--aspects from materials and theoretical
      chemistry.
AB  - Predictions of future climate change have triggered a search for ways to reduce
      the release of greenhouse gases into the atmosphere. Carbon capture and storage
      (CCS) assists this goal by reducing carbon dioxide emissions, and CO(2)
      adsorbents in particular can reduce the costs of CO(2) capture. Here, we review
      the nanoscale sorbent materials that have been developed and the theoretical
      basis for their function in CO(2) separation, particularly from N(2)-rich flue
      gases.

PMID- 20680201
TI  - Electrochemically powered self-propelled electrophoretic nanosubmarines.
AB  - In the past few years, we have witnessed rapid developments in the realization of
      the old nanotechnology dream, autonomous nanosubmarines. These nanomachines are
      self-powered, taking energy from their environment by electrocatalytic conversion
      of chemicals present in the solution, self-propelled by flux of the electrons
      within the submarine and the hydronium ions on the surface of the nanosub,
      powering it in the direction opposite to that of the flux of the hydronium. These
      nanosubmarines are responsive to external fields, able to follow complex magnetic
      patterns, navigate themselves in complex microfluidic channels, follow chemical
      gradients, carry cargo, and communicate with each other. This minireview focuses
      on a discussion of the fundamentals of the electrophoretic mechanism underlying
      the propulsion of this sort of nanosub, as well as a demonstration of the proof
      of-concept capabilities of nanosubmarines.

PMID- 20680202
TI  - Antimicrobial biomaterials based on carbon nanotubes dispersed in poly(lactic-co
      glycolic acid).
AB  - Biomaterials that inactivate microbes are needed to eliminate medical device
      infections. We investigate here the antimicrobial nature of single-walled carbon
      nanotubes (SWNTs) incorporated within the biomedical polymer poly(lactic-co
      glycolic acid) (PLGA). We find Escherichia coli and Staphylococcus epidermidis
      viability and metabolic activity to be significantly diminished in the presence
      of SWNT-PLGA, and to correlate with SWNT length and concentration (<2% by
      weight). Up to 98% of bacteria die within one hour on SWNT-PLGA versus 15-20% on
      pure PLGA. Shorter SWNTs are more toxic, possibly due to increased density of
      open tube ends. This study demonstrates the potential usefulness of SWNT-PLGA as
      an antimicrobial biomaterial.

PMID- 20680207
TI  - Shrink film patterning by craft cutter: complete plastic chips with high
      resolution/high-aspect ratio channel.
AB  - This paper presents a rapid, ultra-low-cost approach to fabricate microfluidic
      devices using a polyolefin shrink film and a digital craft cutter. The shrinking
      process (with a 95% reduction in area) results in relatively uniform and
      consistent microfluidic channels with smooth surfaces, vertical sidewalls, and
      high aspect ratio channels with lateral resolutions well beyond the tool used to
      cut them. The thermal bonding of the layers results in strongly bonded devices.
      Complex microfluidic designs are easily designed on the fly and protein assays
      are also readily integrated into the device. Full device characterization
      including channel consistency, optical properties, and bonding strength are
      assessed in this technical note.

PMID- 20680208
TI  - Microfluidics without pumps: reinventing the T-sensor and H-filter in paper
      networks.
AB  - Conventional microfluidic devices typically require highly precise pumps or
      pneumatic control systems, which add considerable cost and the requirement for
      power. These restrictions have limited the adoption of microfluidic technologies
      for point-of-care applications. Paper networks provide an extremely low-cost and
      pumpless alternative to conventional microfluidic devices by generating fluid
      transport through capillarity. We revisit well-known microfluidic devices for
      hydrodynamic focusing, sized-based extraction of molecules from complex mixtures,
      micromixing, and dilution, and demonstrate that paper-based devices can replace
      their expensive conventional microfluidic counterparts.

PMID- 20680209
TI  - Sequential microfluidic flow synthesis of CePO4 nanorods decorated with emission
      tunable quantum dots.
AB  - CePO(4) nanorods decorated with QDs (QDs@CePO(4)) can be prepared in a
      sequential, aqueous procedure under continuous flow using a rotating tube
      processor and a narrow channel reactor. The emission from the QD@CePO(4) is
      tunable from green to red by simply adjusting the feeding rate, which in turn
      regulates the particle size of the QDs. The Ce(3+) ions in the QDs@CePO(4) serve
      as an efficient fluorescence resonance energy transfer (FRET) donor, effectively
      enlarging the Stokes shift of the QDs.

PMID- 20680211
TI  - High fidelity vinyl terminated polymers by combining RAFT and cobalt catalytic
      chain transfer (CCT) polymerization methods.
AB  - In this work, we combine reversible addition fragmentation transfer
      polymerization (RAFT) with cobalt catalytic chain transfer (CCT) to obtain omega
      unsaturated polymers with relatively low polydispersity values.

PMID- 20680210
TI  - Potassium carbonate-silica: a highly effective stationary phase for the
      chromatographic removal of organotin impurities.
AB  - Organotin impurities in product mixtures can be reduced from stoichiometric
      levels to approximately 15 parts per million by column chromatography using 10%
      w/w anhydrous potassium carbonate-silica as a stationary phase.

PMID- 20680212
TI  - An efficient preparation of indolizines through a tandem palladium-catalyzed
      cross-coupling reaction and cycloisomerization.
AB  - An efficient synthetic method for producing indolizines through a tandem Pd
      catalyzed selective allenyl cross-coupling reaction using organoindium reagents
      and cycloisomerization was developed in a one-pot process.

PMID- 20680213
TI  - Overruling the energy gap law: fast triplet formation in 6-azauracil.
AB  - The photophysical properties of 6-azauracil were studied by means of ab initio
      quantum chemical methods. On the basis of our calculations we propose here the
      following mechanism for the lack of fluorescence and the high triplet quantum
      yield that was observed experimentally after irradiation of this compound with UV
      light [Kobayashi et al., J. Phys. Chem. A, 2008, 112, 13308]. Multiple potential
      energy surface crossings between excited singlet states of pi->pi* and n->pi*
      character lead to an ultrafast transfer of the S(2) ((1)pi->pi*) population to
      the lower-lying S(1) ((1)n->pi*) state. This state acts as a doorway state from
      which the T(1) ((3)pi->pi*) state is formed approximately within 125 ps in the
      isolated 6-azauracil and within 30 ps in acetonitrile solution according to our
      calculations. The enhancement of the S(1)[radiolysis arrow - arrow with voltage
      kink] T(1) intersystem crossing in acetonitrile solution is noteworthy as it goes
      along with an increased adiabatic energy gap between the interacting states. Blue
      shift of the S(1) potential energy surface by about 0.2 eV in this polar, aprotic
      environment places the intersection between the S(1) and T(1) potentials close to
      the S(1) minimum, thus increasing the overlap of the vibrational wavefunctions
      and consequently speeding up the spin-forbidden nonradiative transition.

PMID- 20680214
TI  - Self-templated and self-assembled synthesis of nano/microstructures of Gd-based
      rare-earth compounds: morphology control, magnetic and luminescence properties.
AB  - Nearly monodisperse NaGdF(4) and GdF(3) nanowires/nanorods as well as GdBO(3)
      microplates/microflowers have been successfully prepared by a designed chemical
      conversion approach using Gd(OH)(3) nanowires/nanorods as precursors via a facile
      hydrothermal approach. The Gd(OH)(3) nanowires/nanorods precursors were prepared
      through a simple hydrothermal process, which then served as sacrificial templates
      for the fabrication of NaGdF(4) and GdF(3) nanowires/nanorods as well as GdBO(3)
      microplates/microflowers by a hydrothermal process. The possible formation
      mechanisms for the corresponding Gd(3+)-based various products are presented in
      detail. We have investigated the magnetic properties of the NaGdF(4), GdF(3), and
      GdBO(3) samples. The as-obtained Eu(3+) doped NaGdF(4), GdF(3), and GdBO(3)
      samples show the strong characteristic red emission of Eu(3+) under ultraviolet
      excitation. Moreover, the luminescence colors of the Eu(3+) and Tb(3+) co-doped
      GdBO(3) samples can be tuned from red, through orange, yellow and green-yellow,
      to green by simply adjusting the relative doping concentrations of the activator
      ions under a single wavelength excitation, which might find potential
      applications in the fields such as light display systems and optoelectronic
      devices. More importantly, this simple method is expected to allow the large
      scale production of other complex rare-earth compounds with controllable
      morphologies and sizes, and exploration of the morphology and phase-dependent
      photoluminescence properties.

PMID- 20680215
TI  - The first observation of azo-hydrazone and cis-trans tautomerisms for disperse
      yellow dyes and their nickel(II) and copper(II) complexes.
AB  - Azo-hydrazone and cis-trans tautomerisms have been firstly observed between two
      disperse yellow dyes (cis/trans-HL(1) and cis-HL(2)) and three neutral dye-metal
      complexes (one mononuclear Ni(II) complex 3 and two Cu(II) coordination polymers
      4 and 5 formulated as [Ni(trans-L(1))(2)(CH(3)OH)(2)].2H(2)O, [Cu(cis
      L(1))(2)](n) and [Cu(L(3))(H(2)O)](n)).

PMID- 20680216
TI  - Polynuclear manganese amino acid complexes.
AB  - The reaction of MnCl(2).4H(2)O with DL-valine (Val) in MeOH in the presence of Et
      saoH(2) (2-hydroxypropiophenone oxime) and NEt(4)OH forms the complex
      [Mn(III)(3)Mn(IV)(2)O(2)(CH(3)O)(Et-sao)(6)(Val)].Val.1.5H(2)O (1.Val.1.5H(2)O)
      in very good yields. A similar reaction of MnCl(2).4H(2)O with Glycine (Gly) in
      MeOH in the presence of saoH(2) (salicylaldoxime) and Ca(OH)(2) yields the
      complex [Mn(III)(3)O(sao)(3)(Gly)Cl(MeOH)(3)].1.87 MeOH.0.13H(2)O (2.1.87
      MeOH.0.13H(2)O). Replacing saoH(2) with Me-saoH(2) (2-hydroxyethanone oxime) and
      Gly with HPABA (para-aminobenzoic acid) in the presence of CH(3)ONa in MeOH forms
      the complex [Mn(6)O(2)(PABA)(2)(Me
      sao)(6)(MeOH)(4)(H(2)O)(2)].2[Mn(6)O(2)(PABA)(2)(Me-sao)(6)(MeOH)(2)].11 MeOH
      (3.11 MeOH) in moderate yields. Magnetic studies for 1 and 2 reveal the presence
      of both ferromagnetic and antiferromagnetic interactions, leading to S = 2 ground
      states for both complexes. Complexes 1 and 2 represent the first examples of
      polynuclear manganese complexes with any naturally occurring alpha-amino acid,
      while 3 is the first structurally characterised example of a manganese para
      aminobenzoate complex.

PMID- 20680217
TI  - Electrochemical impedance study of the interaction of metal ions with unlabeled
      PNA.
AB  - The interactions of the metal ions Mg(2+), Zn(2+), Ni(2+), and Co(2+) with thin
      films of peptide nucleic acids (PNAs) were studied by electrochemical impedance
      spectroscopy (EIS), and the results show that Zn(2+), Ni(2+) and Co(2+)
      interacted favorably with the PNA film involving the backbone and the nucleobases
      with the exception of Mg(2+) for which the interaction with the backbone appears
      to be dominant.

PMID- 20680218
TI  - Self-assembly of nanometre-scale metallacalix[4]arene building blocks and Keggin
      units to a novel (3,4)-connected 3D self-penetrating framework.
AB  - A novel (3,4)-connected 3D self-penetrating metal-organic framework with a
      nanometre-scale cavity constructed from metallacalix[4]arene building blocks and
      Keggin-type polyanions has been obtained by using a 1,3-bis(1-methyl-5-mercapto
      1,2,3,4-tetrazole)propane ligand.

PMID- 20680219
TI  - Total synthesis of grassypeptolide.
AB  - The first total synthesis of grassypeptolide, an anticancer cyclodepsipeptide
      isolated from marine cyanobacteria, has been achieved in 17 steps and an overall
      11.3% yield.

PMID- 20680220
TI  - Molecularly imprinted nanotubes for enantioselective drug delivery and controlled
      release.
AB  - Molecularly imprinted nanotubes for enantioselective drug delivery and controlled
      release are fabricated by the combination of template synthesis and ATRP
      grafting. The release of R-propranolol from the imprinted nanotubes in rats is
      restricted while the release of pharmacologically active S-enantiomer is greatly
      promoted.

PMID- 20680221
TI  - Electrophilic activation and the formation of an unusual Tl+/Cr3+ tetranuclear
      ion-complex adduct.
AB  - Reaction of TlPF(6) with the Cr(III) complex fac-[CrCl(3)(NPN)] (NPN = bis(2
      picolyl)phenyl phosphine) did not lead to precipitation of TlCl but rather to
      addition of the Tl(+) cation to the CrCl(3) moiety, which resulted in a pseudo
      dimeric adduct which has an unusual tetranuclear centrosymmetric structure in the
      solid state.

PMID- 20680222
TI  - Initial employment of di-2-pyridyl ketone as a route to
      nickel(II)/lanthanide(III) clusters: triangular Ni(2)Ln complexes.
AB  - Using monoanionic forms of di-2-pyridyl ketone as the only primary ligand,
      triangular Ni(2)M (M = lanthanide, Y) complexes with interesting magnetic
      properties have been synthesized.

PMID- 20680223
TI  - Half-sandwich NHC-nickel(II) complexes as pre-catalysts for the fast Suzuki
      coupling of aryl halides: a comparative study.
AB  - Cationic half-sandwich nickel complexes of general formula [Ni(NHC)(NCMe)(eta(5)
      C5R5)](PF6) [NHC = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene (IPr) a, 1,3
      bis(2,4,6-trimethylphenyl)imidazol-2-ylidene (IMes) b; R = H, Me] were prepared
      from the reaction of their neutral homologues [Ni(NHC)Cl(eta(5)-C5R5)] with 1
      equiv. of KPF6 in acetonitrile at room temperature. The new cationic complexes
      [Ni(IPr)(NCMe)(eta(5)-C5Me5)](PF6) 3a, [Ni(IMes)(NCMe)(eta(5)-C5Me5)](PF6) 3b and
      [Ni(IMes)(NCMe)(eta(5)-C5H5)](PF6) 4b were obtained in high yield and were fully
      characterized by 1H and 13C NMR spectroscopy, IR spectroscopy, elemental
      analyses, and in the case of 3a by a single-crystal X-ray diffraction study. The
      neutral analogue of 3a, [Ni(IPr)Cl(eta(5)-C5Me5)] 1a was also structurally
      characterized. Their geometries were compared and no significant structural
      differences were observed. Nevertheless solution NMR spectroscopy established
      that the acetonitrile ligand of the cationic species is labile in solution. This
      results in the absence of any rotational significant barrier about the nickel
      carbene carbon bond at ambient temperature in solution in the sterically
      congested cationic complexes 3a and 3b, in contrast to their neutral analogues 1a
      and [Ni(IMes)Cl(eta(5)-C5Me5)] 1b. The neutral and the cationic complexes
      catalyzed the cross-coupling of phenylboronic acid with aryl halides in the
      absence of co-catalysts or reductants. Surprisingly, the neutral or cationic
      nature of the complexes proved to have almost no influence on the reaction yields
      and rates. However, complexes bearing the bulky electron-rich
      pentamethylcyclopentadienyl ligand were much more active than those bearing the
      cyclopentadienyl ligand, and TOF of up to 190 h(-1), a high rate for nickel(II)
      complexes under similar conditions, were observed with these species.

PMID- 20680224
TI  - Synthesis, characterisation and biological evaluation of N-(ferrocenyl)naphthoyl
      amino acid esters as anticancer agents.
AB  - A series of N-(ferrocenyl)naphthoyl amino acid esters 5-18 has been prepared by
      coupling ferrocenyl naphthoic acids 3-4 to alpha-amino acids and linear amino
      acids in the presence of N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide
      hydrochloride (EDC) and 1-hydroxybenzotriazole (HOBt). The compounds were fully
      characterised by a range of NMR spectroscopic techniques, UV-Vis spectroscopy,
      mass spectrometry and cyclic voltammetry. X-ray crystallographic studies of the
      intermediate compounds 1-2 were also performed. Biological evaluation of the
      intermediates 1-2 and N-(ferrocenyl)naphthoyl amino acid esters 5-18 was
      performed in the H1299 non-small cell lung cancer (NSCLC) cell line and the Sk
      Mel-28 metastatic melanoma cell line. The intermediates 1-2 failed to produce an
      effect in either cell line. Compounds 5-18 exhibited a strong anti-proliferative
      effect in the H1299 cell line, whilst the Sk-Mel-28 cells were slightly more
      resistant to these compounds. N-(6-ferrocenyl-2-naphthoyl)-gamma-aminobutyric
      acid ethyl ester 17 shows a particularly high activity in both the H1299 cell
      line (IC(50) = 0.62 +/- 0.07 microM) and the Sk-Mel-28 cell line (IC(50) = 1.41
      +/- 0.04 microM).

PMID- 20680225
TI  - Fabrication and growth mechanism of three-dimensional spherical TiO(2)
      architectures consisting of TiO(2) nanorods with {110} exposed facets.
AB  - In this paper, we report on the fabrication of a novel rutile TiO(2) architecture
      consisting of nanorods with {110} exposed facets through a simple hydrothermal
      method without using any templates. An outside-in ripening mechanism is proposed
      to account for the formation of the TiO(2) architectures.The formation of the
      TiO(2) architectures can be attributed to the Ostwald step rule and highly acidic
      medium. Significantly, the current method is suitable for high-yield (>98%)
      production of the TiO(2) architectures with nearly 100% morphological yield. This
      research provides a facile route to fabricate rutile TiO(2) with three
      dimensional microstructures based on nano units. It is easy to realize their
      industrial-scale synthesis and application because of the simple synthesis
      method, low cost, and high yield.

PMID- 20680226
TI  - Phototransport in networks of tetrapod-shaped colloidal semiconductor
      nanocrystals.
AB  - Tetrapod-shaped CdSe(core)/CdTe(arms) colloidal nanocrystals, capped with
      alkylphosphonic acids or pyridine, were reacted with various small molecules
      (acetic acid, hydrazine and chlorosilane) which induced their tip-to-tip assembly
      into soluble networks. These networks were subsequently processed into films by
      drop casting and their photoconductive properties were studied. We observed that
      films prepared from tetrapods coated with phosphonic acids were not
      photoconductive, but tip-to-tip networks of the same tetrapods exhibited
      appreciable photocurrents. On the other hand, films prepared from tetrapods
      coated with pyridine instead of phosphonic acids were already highly
      photoconductive even if the nanocrystals were not joined tip-to-tip. Based on the
      current-voltage behavior under light we infer that the tunneling between
      tetrapods is the dominant charge transport mechanism. In all the samples,
      chemically-induced assembly into networks tended to reduce the average tunneling
      barrier. Additionally, pyridine-coated tetrapods and the tip-to-tip networks made
      out of them were tested as active materials in hybrid photovoltaic devices.
      Overall, we introduce an approach to chemically-induced tip-to-tip assembly of
      tetrapods into solution processable networks and demonstrate the enhancement of
      electronic coupling of tetrapods by various ligand exchange procedures.

PMID- 20680227
TI  - FXIII deficiency due to base exchange Thr 449 (ACT) --> Ile (ATT) in exon 11 of
      the factor 13A gene. A cause of bleeding?
AB  - A 17-year old man was sent to us for coagulation testing because he suffered from
      acute bleeding which started immediately after making an incision in the skin for
      a urological surgery. The patient had a history of mild bleeding symptoms (nose
      bleeds during the childhood, gingival bleeds). Results of laboratory
      investigations: Blood group 0, closure times (PFA 100):132 s (ADP/collagen) and
      300 s (epinephrine/collagen), VWF antigen 57%, VWF activity 50%, factor VIII
      activity 66%, factor XIII activity 59%. The results were confirmed by further
      investigations. Additionally, two relevant genetic findings were obtained: first
      a heterozygous base exchange in exon 11 of the factor 13A gene -Thr 449 (ACT)>Ile
      (ATT)-, not described before the completion of the study, and second the
      homozygous state of the 807 C-allele within the integrin alpha2 gene. The patient
      inherited the base exchange in the factor 13A gene from his mother. Homozygosity
      of the 807 C allele in the integrin alpha2 gene is associated with a very low
      expression of the platelet collagen receptor. Individuals with low VWF due to
      blood group 0 and low platelet collagen receptor density often exhibit a bleeding
      tendency, e.g. bleedings from mucosal membranes or menorrhagia in females.
      CONCLUSION: In our opinion the light factor XIII deficiency in our patient is
      coincidental and not the sole cause of bleeding.

PMID- 20680228
TI  - The role of glycoprotein Ibalpha and von Willebrand factor interaction in stroke
      development.
AB  - Ischaemic stroke is a devastating disease with limited treatment options due to
      numerous uncertainties regarding the underlying pathophysiology. The contribution
      of glycoprotein (GP)Ibalpha and von Willebrand factor (VWF) in stroke development
      has only recently been established in mice. Complete blockade of GPIbalpha led to
      a significant reduction of infarct volumes in mice undergoing one hour of
      transient middle cerebral artery occlusion (tMCAO). High shear-induced changes in
      VWF confirmation are a prerequisite for VWF binding to collagen and GPIbalpha
      expressed on platelets. Importantly, transgenic VWF-/- mice were similarly
      protected against ischemic stroke after tMCAO, and hydrodynamic injection of a
      VWF-encoding plasmid restored VWF serum levels and the susceptibility towards
      stroke. Secreted VWF is rapidly cleaved by ADAMTS13. Accordingly, ADAMTS13
      deficient mice developed larger infarction after tMCAO, while infusion of
      recombinant ADAMTS13 into wild-type mice was stroke-protective. In conclusion,
      there is compelling evidence that GPIbalpha/VWF interactions and downstream
      signaling via phospholipase D1 (PLD1) provide new therapeutic targets in ischemic
      stroke.

PMID- 20680229
TI  - Von Willebrand disease and Weibel-Palade bodies.
AB  - Von Willebrand factor (VWF) is a pivotal haemostatic protein mediating platelet
      adhesion to injured endothelium and carrying coagulation factor VIII (FVIII) in
      the circulation to protect it from premature clearance. Apart from the roles in
      haemostasis, VWF drives the formation of the endothelial cell specific Weibel
      Palade bodies (WPBs), which serve as a regulated storage of VWF and other
      thrombotic and inflammatory factors. Defects in VWF could lead to the bleeding
      disorder von Willebrand disease (VWD). Extensive studies have shown that several
      mutations identified in VWD patients cause an intracellular retention of VWF.
      However, the effects of such mutations on the formation and function of its
      storage organelle are largely unknown. This review gives an overview on the role
      of VWF in WPB biogenesis and summarizes the limited data on the WPBs formed by
      VWD-causing mutant VWF.

PMID- 20680230
TI  - Arterial thrombus formation. Novel mechanisms and targets.
AB  - Platelet and coagulation factor-dependent thrombus formation is critical to limit
      posttraumatic blood loss at sites of vascular injury. However, under pathological
      conditions like rupture of an atherosclerotic plaque, it may also lead to vessel
      occlusion causing myocardial infarction or stroke. Therefore, antithrombotic
      treatment is the prime therapeutic option in the prophylaxis and treatment of
      ischaemic cardio- and cerebrovascular diseases. The use of existing
      antithrombotic agents is, however, limited by their inherent effect on primary
      haemostasis. In recent years, major advances have been made in understanding the
      mechanisms of thrombus formation in haemostasis and thrombosis and some studies
      raised the interesting possibility that occlusive thrombus formation and
      haemostasis may involve partially different mechanisms. This review briefly
      summarizes these developments and highlights newly identified mechanisms involved
      in platelet adhesion and activation, intracellular calcium signaling, integrin
      activation and initiation of coagulation. The suitability of these pathways as
      novel targets for antithrombotic therapy is discussed.

PMID- 20680231
TI  - Alternatively spliced tissue factor. A crippled protein in coagulation or a key
      player in non-haemostatic processes?
AB  - Full-length tissue factor (flTF) initiates coagulation, but also exerts non
      hemostatic functions such as inflammation and angiogenesis through protease
      activated receptors (PARs). In 2003 a soluble variant of flTF was described which
      results from alternative splicing. Since its discovery the role of alternatively
      spliced tissue factor (asTF) in coagulation has been debated. asTF may have pro
      coagulant properties but due to structural differences when compared to flTF,
      asTF coagulant function may be relatively low. Nevertheless, similar to flTF,
      asTF appears to have non-hemostatic properties; asTF expression in tumors
      correlates with increased tumor size, vessel number and poor survival in some
      cancer types, and drives tumor growth in animal models. Interestingly, unlike
      flTF, asTF does not promote angiogenesis through activating PARs but rather via
      integrin ligation. flTF is a critical determinant in cardiovascular disease but
      little is known about asTF in cardiovascular disease. asTF is produced by
      monocytes and macrophages, thus macrophage-derived asTF may contribute to
      atherosclerotic disease. In conclusion, unraveling asTF's non-hemostatic
      properties may generate new insights in the pathophysiology and diagnostics of
      cancer and cardiovascular disease.

PMID- 20680232
TI  - Clinical features and outcome of acquired haemophilia A. Interim analysis of the
      Dusseldorf study.
AB  - We have performed a monocenter study on 29 consecutive patients with acquired
      haemophilia A who were referred for diagnosis and treatment to the Dusseldorf
      Haemophilia Comprehensive Care Center between March 2001 and February 2010.
      PATIENTS, METHODS: 18 men (age: 44-86 years) and 11 women (age: 20-83 years). For
      laboratory evaluation, a standardized staged protocol of aPTT, FVIII:C activity
      and concentration, mixing studies with patient and normal plasma, and
      quantification of inhibitor titers (Bethesda assay) was used. Diagnostic work-up
      included elaborate examinations for any underlying disease. RESULTS: In 18 (62%)
      of the 29 patients with acquired haemophilia A, an underlying disorder was
      identified, including 9 patients with respiratory diseases (31%), 7 patients with
      autoimmune disorders (24%), one with malignancy, and one with postpartum state,
      while in 11 patients (38%) acquired haemophilia A remained idiopathic.
      Haemotherapy of bleeding, suppression or elimination of the inhibitor, and
      induction of immunotolerance to endogenous FVIII:C were performed according to a
      treatment algorithm. Predefined clinical endpoints were control of bleeding,
      eradication of the inhibitor, complete or partial remission (CR, PR), relapse, or
      early death (< or =30 days). Of the 29 patients in total, 22 individuals achieved
      CR (76%), three had PR, one relapsed, and three died within 30 days (one of acute
      myocardial infarction while on antihaemorrhagic treatment, one of sepsis while on
      immunosuppression due to active acquired haemophilia A, one of lung bleeding in
      association with pre-existing pulmonary sarcoidosis). CONCLUSION: This monocenter
      study demonstrates that control of life-threatening bleeding, eradication of the
      inhibitor, and induction of tolerance to endogenous FVIII have significantly
      improved the clinical outcome of acquired haemophilia A. Our data also suggest a
      shift in underlying disorders associated with acquired haemophilia A, whereby, in
      comparison to published studies, a relative increase in the proportion of
      patients with respiratory diseases is present.

PMID- 20680233
TI  - Antiphospholipid syndrome. Current insights into laboratory diagnosis and
      pathophysiology.
AB  - The antiphospholipid syndrome (APS) is a non-inflammatory autoimmune disease
      characterized by the presence of antiphospholipid antibodies (aPL) in the plasma
      of patients with vascular thrombosis, recurrent complications of pregnancy, or
      both (1, 2). The presence of aPL in plasma of patients can be detected with
      either a prolongation of phospholipid dependent coagulation tests (lupus
      anticoagulant, LAC), or with solid phase immune assays against the protein beta2
      glycoprotein I (beta2-GPI) or the phospholipid cardiolipin (anti-beta2-GPI
      antibody ELISA and anti-cardiolipin antibody ELISA, respectively) (3). For a long
      time there was a lot of confusion on who had the syndrome and who not. To solve
      this dispute, an international consensus meeting was organized in Sapporo in 1999
      to formulate classification criteria for patients with the antiphospholipid
      syndrome (4). These criteria have been updated in 2004 at another international
      consensus meeting in Sydney (5). The classification criteria were defined for
      scientific purposes and were aimed to be used as inclusion criteria in patient
      related studies. They were specifically not defined for diagnostic purposes.
      However, current practice is that these criteria are used as a diagnostic tool.
      This is very unfortunate because the specificity of the different aPL assays to
      detect the clinical manifestations that characterize APS are disputable. One of
      the aims of defining the criteria was to initiate studies to determine the value
      of the different anti-phospholipid antibody assays to serve as biomarker for the
      risk of thrombosis and pregnancy morbidity. The recent progress made on this
      important topic will be discussed.

PMID- 20680234
TI  - State-of-the-art in haemostaseology.

PMID- 20680235
TI  - What is the role of pulse oximetry in the assessment of patients with community
      acquired pneumonia in primary care?
AB  - INTRODUCTION: Community-acquired pneumonia (CAP) is a common presenting condition
      in primary care. Assessment of oxygenation status using pulse oximetry is
      increasingly available, but its precise role in disease severity assessment is
      unknown. AIMS: To inform the use of pulse oximetry in patients with CAP,
      including the utility of different oxygenation thresholds, patient subgroups, and
      interaction with existing severity scores. METHODS: A prospective cohort study of
      adults with CAP admitted to a UK teaching hospital trust. Oxygen saturations
      (SpO2) and the fraction of inspired oxygen were recorded on admission. The value
      of different SpO2 thresholds (< 88%, <= 90%, <= 92%, and < 95%) in predicting 30
      day mortality and critical care admission was analysed. RESULTS: 467 patients had
      SpO2 measured on room air. Admission SpO2 <= 90% was observed in 28% of patients
      and had reasonable specificity (76%) for 30-day mortality or critical care
      admission, but low sensitivity (46%). Specificity was particularly good for
      adults <50 years of age (90%) or those with asthma (92.3%). CONCLUSION: SpO2 <=
      90% has good specificity but low sensitivity for adverse outcomes in CAP. It
      complements rather than replaces clinical severity scoring.

PMID- 20680236
TI  - Knowledge and utilisation of occupational asthma guidelines in primary care.
AB  - AIMS: To develop an occupational asthma learning module, which could be used both
      as an educational tool and to evaluate awareness and usage of clinical guidelines
      in primary care. METHODS: Healthcare professionals were invited to undertake an
      interactive BMJ Learning module, developed from existing national occupational
      asthma guidelines. Participants were invited to record immediate post-module
      feedback, and were also sent an e-mail questionnaire six weeks later to assess
      the impact of the module. RESULTS: In total 1041 healthcare professionals
      completed the learning module within the first six months, which was associated
      with significant improvements in knowledge, and predominantly positive feedback.
      The e-mail follow-up questionnaire demonstrated improved usage and awareness of
      national occupational asthma guidelines. CONCLUSIONS: Significant barriers remain
      in ensuring that evidence-based occupational medicine guidelines are adopted in
      primary care. This project has demonstrated that e-learning offers one method of
      improving postgraduate medical education in this area, particularly where
      evidence-based guidelines have already been developed.

PMID- 20680237
TI  - Management of allergic and non-allergic rhinitis: a primary care summary of the
      BSACI guideline.
AB  - Rhinitis is a common problem in primary care which is often managed sub
      optimally. It causes considerable morbidity and has been shown to have a
      detrimental impact on people's ability to concentrate at school and at work.
      Rhinitis and asthma often present together, and symptomatic rhinitis can be
      associated with poor asthma control and increased risk of exacerbations. There is
      therefore a clear need to recognise and treat rhinitis according to guideline
      recommendations. This article is a primary care summary of the British Society
      for Allergy & Clinical Immunology (BSACI) Standards of Care Committee guideline
      on the management of rhinitis, written by a multi-disciplinary group of
      clinicians. It takes into account the time restrictions on assessment and the
      tests and equipment available in primary care, as well as the need for practical,
      clear and intuitive strategies for investigation and management. It recommends a
      stepwise approach to treatment, and highlights the relevance of less frequently
      prescribed treatments, including nasal douching leukotriene receptor antagonists
      and anticholinergics. Red flag symptoms are identified, together with indicators
      for referral. As with many other long term conditions, good communication between
      primary and secondary care in terms of timely and appropriate referral is a key
      factor for success.

PMID- 20680238
TI  - [Brachytherapy for the treatment of head and neck cancer].
AB  - Image-Adapted brachytherapy (IABT) is a modern interdisciplinary development of
      classic radiation therapy, which allows the application of a high radiation dose
      while avoiding severe adverse events, thereby improving the prognosis of our
      patients. Indications in head and neck squamous cell carcinoma (HNSCC) include
      tumours of the floor of mouth, the face, the paranasal sinuses, the naso- and
      oropharynx, recurrent cancer and incomplete resections due to close vicinity of
      the tumor to important structures. The application type can be classified as
      curative, adjuvant, perioperative as a boost with or without external beam
      radiation (EBRT) or as a palliative treatment. The published results encourage
      the integration of IABT as part of the therapy of HNSCC, thereby improving the
      prognosis and quality of life of our patients.

PMID- 20680239
TI  - [Classification and management of upper gastrointestinal bleeding].
AB  - The upper gastrointestinal bleeding remains the most frequent emergency in
      gastroenterology. Due to the different therapeutic approach a distinction between
      the variceal and the non-variceal bleeding has been established. A risk
      assessment for the individual patient is crucial for timing of the endoscopic
      procedure as well as for the estimation of prognosis. This review gives an
      overview on modern therapeutic techniques for both, variceal and non-variceal
      bleeding highlighting on success rates but also on potential complications of the
      different therapeutic interventions.

PMID- 20680240
TI  - [Revision strategy after failure of Magerl-Gallie fusion procedure].
AB  - For failure of an implant after a Magerl-Gallie stabilization procedure and
      detection of pseudarthrosis with instability of segments C1 and C2, operative
      revision and restabilization are necessary in the majority of cases. The
      following case report summarizes a revision strategy using a modified Goel-Harms
      procedure to restabilize a persisting C1-C2 instability after a failed Magerl
      Gallie fusion procedure. This was necessary because of breakage of both
      transarticular C1-C2 screws with incompletely consolidated atlanto-axial fusion
      and persisting C1-C2 instability.

PMID- 20680241
TI  - [Fractures of the extremities with severe open soft tissue damage. Initial
      management and reconstructive treatment strategies].
AB  - The successful management of open extremity injuries continues to represent a
      surgical challenge requiring a structured and multidisciplinary treatment
      concept. The treatment strategy depends on specific parameters, including the
      overall injury severity, life threatening trauma components, the degree oft soft
      tissue injury, the ischemia time, the contamination of the wound as well as the
      age and accompanying diseases of the patient. The treatment of fractures with a
      high-grade open soft tissue injury is guided by the severity of soft tissue
      damage including neurovascular damages, type of the fracture, overall state of
      the patient and is based on a clearly defined reconstructive algorithm
      sequentially employing initial wound treatment (debridement), stabilisation of
      the fracture and soft tissue coverage. The initial wound management includes
      radical and serial debridements and vessel reconstruction, followed by the
      gradual reconstruction of bone, tendons and nerves and a subsequent plastic soft
      tissue coverage.The sequential and priority-orientated implementation of these
      treatment steps is decisive for the long term outcome, which ideally results in
      an regular healing of bone and soft tissue without the presence of infection and
      good regain of extremity function.

PMID- 20680244
TI  - Soft tissue balance measurement in minimal incision surgery compared to
      conventional total knee arthroplasty.
AB  - PURPOSES: Minimal incision surgery (MIS) total knee arthroplasty (TKA) is widely
      promoted as a possible improvement over conventional TKA, and accurate
      implantations have recently been reported using navigation systems. However, soft
      tissue balance during MIS-TKA remains challenging. Therefore, in this report,
      joint gap (component gap) and ligament balance (varus angle) were assessed during
      MIS-TKA using a tensor, which enables soft tissue balance assessment with a
      reduced patellofemoral joint and femoral component in place. METHODS: Results
      were compared to those of conventional TKA. Posterior stabilized TKA were
      performed in 50 knees (25 knees: MIS-TKA using quadriceps-sparing approach; 25
      knees: conventional TKA using medial parapatellar approach) with varus
      osteoarthritis. Component gap and varus angle were measured using the tensor with
      a reduced patellofemoral joint at 0, 10, 45, 90, and 135 degrees . RESULTS:
      Whereas the component gap in MIS-TKA was significantly larger through the entire
      arc of flexion compared with conventional TKA, the pattern of joint looseness
      showed no difference between the two procedures. The varus angle in MIS-TKA was
      significantly larger than that in conventional TKA at 0, 90, and 135 degrees  of
      knee flexion. CONCLUSIONS: MIS-TKA may lead to ligament imbalance due to the
      difficulties induced by a limited working space. Understanding this pattern
      allows surgeons to be able to adjust the soft tissue balance more accurately and
      thereby expect a better post-operative outcome even in MIS-TKA.

PMID- 20680245
TI  - Serial dilation reduces graft slippage compared to extraction drilling in
      anterior cruciate ligament reconstruction: a randomized controlled trial using
      radiostereometric analysis.
AB  - PURPOSE: This study tested the hypothesis that serial dilation of the tibial
      tunnel could provide a stronger anchorage of the graft-fixation-device complex
      compared to traditional extraction drilling. METHODS: Forty patients (22 men and
      18 women) undergoing ACL reconstruction were randomized to either extraction
      drilling (group ED) or compaction by serial dilation (group SD) of the tibial
      tunnel. Tantalum beads were placed in the tibia, femur, and in the hamstring
      graft. Radiostereometric analysis (RSA) was performed postoperatively and again
      after 6, 12, and 24 weeks. Migration of graft in the bone tunnels as well as knee
      laxity was assessed using RSA and a TELOS stress device. RESULTS: Six patients
      (three men and three women) were excluded during follow-up, which resulted in 17
      patients in group ED [median age 30 years (range 20-50)] and 17 patients in group
      SD [median age 32 years (range 20-49)]. The mean migration of the graft in the
      tibial bone canal after 3 months was 1.3 (SD 0.6) mm in group ED and 0.8 (SD 0.5)
      mm in group SD (P = 0.02). The overall knee laxity after 3 months was 13.0 (SD
      4.0) mm in group ED and 10.9 (SD 3.1) mm in group SD. CONCLUSION: This study
      found less slippage of the hamstring graft in the tibial bone canal in the serial
      dilated group compared to the extraction drilling group. The clinical relevance
      of the difference is unknown. No difference in stress radiographic knee laxity
      was found between the two groups.

PMID- 20680246
TI  - The combination of radiostereometric analysis and the telos stress device results
      in poor precision for knee laxity measurements after anterior cruciate ligament
      reconstruction.
AB  - PURPOSE: Several devices for measuring knee laxity following anterior cruciate
      ligament ACL reconstruction exist, but the precision of the methods has never
      been optimal. Therefore, a new standardized protocol (NSP) was made, aiming at
      ensuring a reliable positioning of the Telos Stress Device (TSD) which
      theoretically could result in precise knee laxity measurements when using
      radiostereometric analysis (RSA) in combination with TSD. METHOD: The TSD was
      applied to the knee of 30 healthy persons, using both the NSP and the official
      company instructions. The position of the stress arms of the TSD was marked
      following each measurement. The reliability of each protocol was calculated as
      the difference in length between the first and second markings. The NSP for the
      TSD was then used in a clinical study. Thirty-five patients underwent ACL
      reconstruction. Double measurements of knee laxity by RSA were performed at a 3
      month follow-up. RESULTS: Using the NSP for TSD positioning, the prediction
      interval at the marking sites ranged from +/-0.4 to +/-1.1 mm. Following the
      company instructions, the prediction interval ranged from +/-0.8 to +/-3.9 mm
      depending on marking site. Thus, the precision of positioning the stress arms of
      the TSD was improved at all marking sites using the NSP compared with the
      original company protocol. The double measurements of the knee laxity in the
      clinical study resulted in a mean difference of 0.0 mm and a prediction interval
      of +/-5.2 mm. CONCLUSION: Even though the NSP improved the positioning of the TSD
      on patients' extremities, the combination of NSP-TSD and RSA was not able to
      provide acceptable knee laxity measurements in a clinical setting compared with
      published precision data for other devices on the market. Therefore, the Telos
      Stress Device is not recommendable for use in knee laxity measurements following
      ACL reconstruction.

PMID- 20680247
TI  - A novel finding of a low-molecular-weight compound, SMTP-7, having thrombolytic
      and anti-inflammatory effects in cerebral infarction of mice.
AB  - Tissue plasminogen activator (t-PA) has a short therapeutic time window for
      administration (3 h) and carries a risk of promoting intracerebral hemorrhage.
      The aim of the present study was to investigate a therapeutic time window and
      frequency of hemorrhagic region by treatment with Stachybotrys microspora
      triprenyl phenol-7 (SMTP-7). Thrombotic occlusion was induced by transfer of
      acetic acid-induced thrombus at the right common carotid artery into the brain of
      mice. Infarction area, neurological score, edema percentage, and regional
      cerebral blood flow (CBF) were determined as the index of the efficacy of SMTP-7.
      In order to evaluate the mechanism of SMTP-7, plasmin activities and the
      expressions of interleukin (IL)-1beta, tumor necrosis factor-alpha (TNF-alpha),
      and IL-6 mRNA were examined. SMTP-7 (0.1, 1, 10 mg/kg) dose dependently reduced
      infarction area, neurological score, and edema percentage. Additionally, its
      therapeutic time window was longer than that of t-PA, a high-molecular-weight
      compound. In addition, little hemorrhagic region was induced by treatment with
      SMTP-7. SMTP-7 showed plasmin activity in vivo and caused a decreased CBF to
      recover. Furthermore, the expressions of inflammatory cytokine mRNA (IL-1beta,
      TNF-alpha, IL-6) were increased by t-PA treatment 3 h after ischemia but were not
      induced by SMTP-7 treatment. These results indicate that SMTP-7 shows potential
      thrombolytic and anti-inflammatory effects as well as a wide therapeutic time
      window and little hemorrhagic region compared with that of t-PA. Therefore, this
      novel low-molecular-weight compound may represent a novel approach for the
      treatment of cerebral infarction.

PMID- 20680248
TI  - Do rats (Rattus norvegicus) perceive biological motion?
AB  - It is unknown whether the rodent visual system can perceive biological motion, an
      ability present in primates, cats, and several bird species. Using a water-maze
      visual discrimination task, we find that rats can be trained to distinguish
      between left- and rightward motion of abstract point-light displays of walking
      humans. However, rats were unable to generalize to a novel point-light display (a
      walking cat), or to a display of a backward walking human, where overall body
      configuration and local, ballistic foot motion provide directly opposing cues
      regarding movement direction. Together, these experiments provide the first
      demonstration of the ability of rodents to extract motion direction cues from
      abstract, point-light displays. However, when isolated, neither the overall body
      configuration nor the local motion of the feet appears to provide sufficient
      information for rats to reliably extract movement direction in biological motion
      displays.

PMID- 20680249
TI  - Movement chunking during sequence learning is a dopamine-dependant process: a
      study conducted in Parkinson's disease.
AB  - Chunking of single movements into integrated sequences has been described during
      motor learning, and we have recently demonstrated that this process involves a
      dopamine-dependant mechanism in animal (Levesque et al. in Exp Brain Res 182:499
      508, 2007; Tremblay et al. in Behav Brain Res 198:231-239, 2009). However, there
      is no such evidence in human. The aim of the present study was to assess this
      question in Parkinson's disease (PD), a neurological condition known for its
      dopamine depletion in the striatum. Eleven PD patients were tested under their
      usual levodopa medication (ON state), and following a 12-h levodopa withdrawal
      (OFF state). Patients were compared with 12 healthy participants on a motor
      learning sequencing task, requiring pressing fourteen buttons in the correct
      order, which was determined by visual stimuli presented on a computer screen.
      Learning was assessed from three blocks of 20 trials administered successively.
      Chunks of movements were intrinsically created by each participant during this
      learning period. Then, the sequence was shuffled according to the participant's
      own chunks, generating two new sequences, with either preserved or broken chunks.
      Those new motor sequences had to be performed separately in a fourth and fifth
      blocks of 20 trials. Results showed that execution time improved in every group
      during the learning period (from blocks 1 to 3). However, while motor chunking
      occurred in healthy controls and ON-PD patients, it did not in OFF-PD patients.
      In the shuffling conditions, a significant difference was seen between the
      preserved and the broken chunks conditions for both healthy participants and ON
      PD patients, but not for OFF-PD patients. These results suggest that movement
      chunking during motor sequence learning is a dopamine-dependent process in human.

PMID- 20680250
TI  - Time course and specificity of sensory-motor alpha modulation during the
      observation of hand motor acts and gestures: a high density EEG study.
AB  - The main aim of the present study was to explore, by means of high-density EEG,
      the intensity and the temporal pattern of event-related sensory-motor alpha
      desynchronization (ERD) during the observation of different types of hand motor
      acts and gestures. In particular, we aimed to investigate whether the sensory
      motor ERD would show a specific modulation during the observation of hand
      behaviors differing for goal-relatedness (hand grasping of an object and
      meaningless hand movements) and social relevance (communicative hand gestures and
      grasping within a social context). Time course analysis of alpha suppression
      showed that all types of hand behaviors were effective in triggering sensory
      motor alpha ERD, but to a different degree depending on the category of observed
      hand motor acts and gestures. Meaningless gestures and hand grasping were the
      most effective stimuli, resulting in the strongest ERD. The observation of social
      hand behaviors such as social grasping and communicative gestures, triggered a
      more dynamic time course of ERD compared to that driven by the observation of
      simple grasping and meaningless gestures. These findings indicate that the
      observation of hand motor acts and gestures evoke the activation of a motor
      resonance mechanism that differs on the basis of the goal-relatedness and the
      social relevance of the observed hand behavior.

PMID- 20680251
TI  - Variance components in discrete force production tasks.
AB  - The study addresses the relationships between task parameters and two components
      of variance, "good" and "bad", during multi-finger accurate force production. The
      variance components are defined in the space of commands to the fingers (finger
      modes) and refer to variance that does ("bad") and does not ("good") affect total
      force. Based on an earlier study of cyclic force production, we hypothesized that
      speeding-up an accurate force production task would be accompanied by a drop in
      the regression coefficient linking the "bad" variance and force rate such that
      variance of the total force remains largely unaffected. We also explored changes
      in parameters of anticipatory synergy adjustments with speeding-up the task. The
      subjects produced accurate ramps of total force over different times and in
      different directions (force-up and force-down) while pressing with the four
      fingers of the right hand on individual force sensors. The two variance
      components were quantified, and their normalized difference was used as an index
      of a total force stabilizing synergy. "Good" variance scaled linearly with force
      magnitude and did not depend on force rate. "Bad" variance scaled linearly with
      force rate within each task, and the scaling coefficient did not change across
      tasks with different ramp times. As a result, a drop in force ramp time was
      associated with an increase in total force variance, unlike the results of the
      study of cyclic tasks. The synergy index dropped 100-200 ms prior to the first
      visible signs of force change. The timing and magnitude of these anticipatory
      synergy adjustments did not depend on the ramp time. Analysis of the data within
      an earlier model has shown adjustments in the variance of a timing parameter,
      although these adjustments were not as pronounced as in the earlier study of
      cyclic force production. Overall, we observed qualitative differences between the
      discrete and cyclic force production tasks: Speeding-up the cyclic tasks was
      associated with better adjustments of the timing accuracy, which helps achieve
      comparable force variance in tasks with different rates of force production. This
      does not happen in discrete tasks. The lack of scaling of the anticipatory
      changes in the synergy index with ramp time is the first reported feature that
      distinguishes anticipatory synergy adjustments from anticipatory postural
      adjustments. We discuss the differences between the cyclic and discrete tasks
      within a hierarchical control scheme offered by Schoner.

PMID- 20680253
TI  - Proposal of a new limited sampling strategy to predict CYP3A activity using a
      partial AUC of midazolam.
AB  - PURPOSE: Midazolam metabolic clearance to 1'-hydroxymidazolam is an accurate
      measure of CYP3A activity which requires extensive plasma and urine sampling. The
      objective of this study was to find a new limited sampling strategy (LSS) to
      predict midazolam metabolic clearance to 1'-hydroxymidazolam and subsequently
      CYP3A activity in an easy and reliable way, reducing costs and labour. METHODS:
      The development of this LSS is based on data from an in vivo drug-drug
      interaction study carried out in our clinical research unit. Various partial AUCs
      of midazolam were calculated and correlated with metabolic clearance of midazolam
      to 1'-hydroxymidazolam by non-linear regression. The correlation with highest r
      (2) values was chosen to predict the midazolam metabolic clearance. Statistical
      significance of this method was verified by calculating the 95% confidence
      interval of the differences (%) between predicted and measured metabolic
      clearance of midazolam to 1'-hydroxymidazolam. RESULTS: The midazolam partial AUC
      from 2 to 4 h after oral administration correlated best with metabolic clearance
      of midazolam to 1'-hydroxymidazolam with r (2) = 0.9816. This partial AUC
      comprised four midazolam concentrations at 2, 2.5, 3 and 4 h after oral
      administration of a midazolam solution. The 95% confidence interval of the
      differences between predicted metabolic clearance and measured metabolic
      clearance of midazolam to 1'-hydroxymidazolam was -0.97 to +13.2. CONCLUSION: The
      determination of the partial AUC using four plasma samples from 2 to 4 h after
      oral administration of a midazolam solution is proposed to be an easy and
      reliable CYP3A phenotyping measure which of course needs to be validated in
      prospective clinical trials.

PMID- 20680252
TI  - With time on our side? Task-dependent compensatory processes in graceful aging.
AB  - Graceful aging has been associated with frontal hyperactivations in working- and
      episodic long-term memory tasks, a compensatory process, according to some, that
      allows the best normal elders to perform these tasks at a juvenile level, in
      spite of natural cortical impoverishment. In this study, 24 young and 24 healthy
      elderly participants were compared. Graceful aging was explored by investigating
      domains where most healthy elders perform like youngers (e.g. lexical-semantic
      knowledge) and tasks that are typically more challenging, like episodic long-term
      recognition memory tasks. With voxel-based morphometry, we also studied to what
      extent changes of fMRI activation were consistent with the pattern of brain
      atrophy. We found that hyperactivations and hypoactivations of the elders were
      not restricted to the frontal lobes, rather they presented with task-dependent
      patterns. Only hypoactivations and normal levels of activation systematically
      overlapped with regional atrophy. We conclude that compensatory processes
      associated with graceful aging may not necessarily be a sign of early saturation
      of executive resources, if this was to be represented by a systematic frontal
      hyperactivation, but rather they may represent the ability of recruiting new
      cognitive strategies. We discuss two possible approaches to further test this
      hypothesis.

PMID- 20680254
TI  - Bilateral anterior uveitis secondary to erlotinib.

PMID- 20680255
TI  - Blood vessel rupture by cavitation.
AB  - Cavitation is thought to be one mechanism for vessel rupture during shock wave
      lithotripsy treatment. However, just how cavitation induces vessel rupture
      remains unknown. In this work, a high-speed photomicrography system was set up to
      directly observe the dynamics of bubbles inside blood vessels in ex vivo rat
      mesenteries. Vascular rupture correlating to observed bubble dynamics were
      examined by imaging bubble extravasation and dye leakage. The high-speed images
      show that bubble expansion can cause vessel distention, and bubble collapse can
      lead to vessel invagination. Liquid jets were also observed to form. Our results
      suggest that all three mechanisms, vessel distention, invagination and liquid
      jets, can contribute to vessel rupture.

PMID- 20680257
TI  - Toxicity of cadmium, anthracene, and their mixture to Desmodesmus subspicatus
      estimated by algal growth-inhibition ISO standard test.
AB  - Cells of Desmodesmus subspicatus 86.81 were used to examine the toxicity of
      cadmium chloride (CdCl(2)) and anthracene (ANT) applied individually and in
      combination. The experiments were performed according to standardized ISO
      (International Organization for Standardization) 8692 protocol (2004). Parameters
      measured were the number of cells and chlorophyll a fluorescence parameters.
      E(r)C(10) and E(r)C(50) values (growth rate [r] inhibition by 10% and 50%,
      respectively) for single toxicants were determined separately. The effect of
      mixtures of the substances (Cd + ANT) at concentrations corresponding to
      E(r)C(10) (E(r)C(10) + E(r)C(10)) and E(r)C(50) (E(r)C(50) + E(r)C(50)) values
      was characterized. The toxicity of individual chemicals after a 72-h exposure was
      as follows: ANT (E(r)C(10) = 0.06; E(r)C(50) = 0.26 mg l(-1)) and CdCl(2)
      (E(r)C(10) = 0.12; E(r)C(50) = 0.30 mg l(-1)). The combination Cd + ANT decreased
      the population growth rate more strongly than the substances applied
      individually. Cadmium at a concentration corresponding to E(r)C(10) slightly
      influenced the parameters of chlorophyll a fluorescence as measured by the OJIP
      test (O, J, I, and P are the different steps of fluorescence induction curve),
      whereas the influence of ANT was not statistically significant. In Cd + ANT
      treated samples, the photosynthetic "vitality" (PI), the maximum quantum yield of
      primary photochemistry (phi(Po)), and the fraction of active PS II reaction
      centre (RC) decreased, but the values of ABS/RC, TR(0)/RC, and DI(0)/RC
      increased. The type of interaction between Cd and ANT depended on the
      concentration of chemicals used. When the substances were applied at
      concentrations of E(r)C(10), synergistic effects were observed, whereas the
      mixture of chemicals used at an E(r)C(50) concentration showed an antagonistic
      interaction.

PMID- 20680256
TI  - The tubular epithelium in the initiation and course of intratubular
      nephrocalcinosis.
AB  - Intratubular nephrocalcinosis is defined as the histological observation of
      calcium oxalate and/or calcium phosphate deposits retained within the lumen of
      the renal tubules. As the tubular epithelium is the primary interaction partner
      of crystals formed in the tubular fluid, the role of the epithelial cells in
      nephrocalcinosis has been investigated intensively. This review summarizes our
      current understanding on how the tubular epithelium mechanistically appears to be
      involved both in the initiation and in the course of nephrocalcinosis, with
      emphasis on in vivo observations.

PMID- 20680258
TI  - High mercury concentrations reflect trophic ecology of three deep-water
      chondrichthyans.
AB  - The relative contributions of proximity to mercury sources and trophic ecology to
      realized axial muscle mercury concentrations were explored for three deep-water
      chondrichthyans (Etmopterus princeps, Centroscymnus coelolepis, and Hydrolagus
      affinis), two species of which are harvested for human consumption. Samples were
      taken at three North Atlantic Ocean locations: the Azores, the Charlie Gibbs
      Fracture Zone, and the Bear Seamount. Despite the long distances between
      anthropogenic sources and the sampling locations, all species from all locations
      had muscle mercury concentrations exceeding the United States human health
      screening value of 0.3 mg/kg wet weight. Proximity to anthropogenic sources was
      not an obvious determinant of these elevated concentrations. Generally, mercury
      concentrations appeared to increase with increased dependence on benthic versus
      pelagic food sources (as indicated by interspecies differences in delta(13)C),
      and with higher position in the trophic web (as indicated by differences in
      delta(15)N).

PMID- 20680259
TI  - Roundup effects on oxidative stress parameters and recovery pattern of Rhamdia
      quelen.
AB  - Antioxidant enzymes and oxidative stress indicators were evaluated in fish
      exposed to different concentrations of the herbicide Roundup 48% (Monsanto, St.
      Louis, MO): control (none), 0.45, or 0.95 mg/l. After exposure for 8 days to
      herbicide, fish were transferred to clean water for a recovery response period
      (also 8 days). Herbicide increased thiobarbituric acid reactive species in liver
      and muscle at the higher concentration and in the brain at both concentrations.
      Protein carbonyl in liver increased after exposure. Catalase (CAT) and superoxide
      dismutase (SOD) activities and ascorbic acid levels in liver did not change in
      fish exposed to both concentrations. Glutathione S-transferase (GST) levels
      decreased at both concentrations. The nonprotein thiol levels decreased at the
      0.95 mg/l concentration. During the recovery period, some of the parameters that
      had altered, such as protein carbonyl content, later recovered. However, some
      enzymes reacted during this period, e.g., GST increased its activity, possibly
      indicating a compensatory response against the toxic conditions. In contrast, CAT
      and SOD activities decreased during the recovery period, indicating herbicide
      toxicity. Oxidative stress that occurred during the exposure period was likely
      due to the increased lipid peroxidation and protein carbonyl content. The results
      concerning oxidative and antioxidant profiles indicate that short-term exposure
      to herbicide is capable of causing oxidative stress in fish tissues.

PMID- 20680260
TI  - Secondary residual shunt after atrial septal defect closure with an amplatzer
      occluder: surgical removal and evaluation of device biocompatibility after 7
      years.
AB  - Interventional occluder implantation has become the preferred mode of treatment
      in children with clinically significant atrial septal defect (ASD). The
      continuous increase in the number of patients treated calls for long-term data on
      device integrity and biocompatibility. We report a child who underwent successful
      interventional ASD closure at age 5 years. Secondary residual shunt occurred
      after 3 years of follow-up, and surgical ASD closure became necessary at age 12
      years. The Amplatzer occluder device, which was removed after 7 years in vivo,
      showed no signs of mechanical failure, corrosion, or clinically relevant
      immunological response at the device-tissue interface.

PMID- 20680262
TI  - Substitution of glutamine by glutamate enhances production and galactosylation of
      recombinant IgG in Chinese hamster ovary cells.
AB  - The effect of ammonia on Chinese hamster ovary (CHO) cell growth and
      galactosylation of recombinant immunoglobulin (rIgG) was investigated using
      shaking flasks with serum free media containing 0-15 mM NH(4)Cl. The elevated
      ammonia inhibited cell growth and negatively affected the galactosylation of
      rIgG. At 15 mM NH(4)Cl, the proportions of monogalactosylated glycan with fucosex
      (monogalactosylated glycan with fucose) and digalactosylated glycan with fucose
      (G2F) were 23.9% and 6.3% lower than those at 0 mM NH(4)Cl, respectively. To
      reduce ammonia formation by cells, glutamate was examined as a substitute for
      glutamine. The use of glutamate reduced the accumulation of ammonia and enhanced
      the production of rIgG while depressing cell growth. At 6 mM glutamate, ammonia
      level did not exceed 2 mM, which is only one third of that at 6 mM glutamine.
      Also, a 1.7-fold increase in the titer of rIgG and specific rIgG productivity, q
      (rIgG), was achieved at 6 mM glutamate. The galactosylation of rIgG was favorable
      at 6 mM glutamate. The proportion of galactosylated glycans, G1F and G2F, at 6 mM
      glutamate was 59.8%, but it was 50.4% at 6 mM glutamine. The use of glutamate
      also increased complement-dependent cytotoxicity activity, one of the effector
      functions of rIgG. Taken together, substitution of glutamine by glutamate can be
      considered relevant for the production of rIgG in CHO cells since glutamate not
      only enhances q (rIgG) but also generates a higher galactosylation essential for
      the effector function of rIgG.

PMID- 20680261
TI  - Genomic architecture of MHC-linked odorant receptor gene repertoires among 16
      vertebrate species.
AB  - The recent sequencing and assembly of the genomes of different organisms have
      shown that almost all vertebrates studied in detail so far have one or more
      clusters of genes encoding odorant receptors (OR) in close physical linkage to
      the major histocompatibility complex (MHC). It has been postulated that MHC
      linked OR genes could be involved in MHC-influenced mate choice, comprising both
      pre- as well as post-copulatory mechanisms. We have therefore carried out a
      systematic comparison of protein sequences of these receptors from the genomes of
      man, chimpanzee, gorilla, orangutan, rhesus macaque, mouse, rat, dog, cat, cow,
      pig, horse, elephant, opossum, frog and zebra fish (amounting to a total of 559
      protein sequences) in order to identify OR families exhibiting evolutionarily
      conserved MHC linkage. In addition, we compared the genomic structure of this
      region within these 16 species, accounting for presence or absence of OR gene
      families, gene order, transcriptional orientation and linkage to the MHC or
      framework genes. The results are presented in the form of gene maps and
      phylogenetic analyses that reveal largely concordant repertoires of gene
      families, at least among tetrapods, although each of the eight taxa studied
      (primates, rodents, ungulates, carnivores, proboscids, marsupials, amphibians and
      teleosts) exhibits a typical architecture of MHC (or MHC framework loci)-linked
      OR genes. Furthermore, the comparison of the genomic organization of this region
      has implications for phylogenetic relationships between closely related taxa,
      especially in disputed cases such as the evolutionary history of even- and odd
      toed ungulates and carnivores. Finally, the largely conserved linkage between
      distinct OR genes and the MHC supports the concept that particular alleles within
      a given haplotype function in a concerted fashion during self-/non-self
      discrimination processes in reproduction.

PMID- 20680263
TI  - (Per)chlorate reduction by an acetogenic bacterium, Sporomusa sp., isolated from
      an underground gas storage.
AB  - A mesophilic bacterium, strain An4, was isolated from an underground gas storage
      reservoir with methanol as substrate and perchlorate as electron acceptor. Cells
      were Gram-negative, spore-forming, straight to curved rods, 0.5-0.8 microm in
      diameter, and 2-8 microm in length, growing as single cells or in pairs. The
      cells grew optimally at 37 degrees C, and the pH optimum was around 7. Strain An4
      converted various alcohols, organic acids, fructose, acetoin, and H(2)/CO(2) to
      acetate, usually as the only product. Succinate was decarboxylated to propionate.
      The isolate was able to respire with (per)chlorate, nitrate, and CO(2). The G+C
      content of the DNA was 42.6 mol%. Based on the 16S rRNA gene sequence analysis,
      strain An4 was most closely related to Sporomusa ovata (98% similarity). The
      bacterium reduced perchlorate and chlorate completely to chloride. Key enzymes,
      perchlorate reductase and chlorite dismutase, were detected in cell-free
      extracts.

PMID- 20680264
TI  - Saccharomyces cerevisiae engineered to produce D-xylonate.
AB  - Saccharomyces cerevisiae was engineered to produce D-xylonate by introducing the
      Trichoderma reesei xyd1 gene, encoding a D-xylose dehydrogenase. D-xylonate was
      not toxic to S. cerevisiae, and the cells were able to export D-xylonate produced
      in the cytoplasm to the supernatant. Up to 3.8 g of D-xylonate per litre, at
      rates of 25-36 mg of D-xylonate per litre per hour, was produced. Up to 4.8 g of
      xylitol per litre was also produced. The yield of D-xylonate from D-xylose was
      approximately 0.4 g of D-xylonate per gramme of D-xylose consumed. Deletion of
      the aldose reductase encoding gene GRE3 in S. cerevisiae strains expressing xyd1
      reduced xylitol production by 67%, increasing the yield of D-xylonate from D
      xylose. However, D-xylose uptake was reduced compared to strains containing GRE3,
      and the total amount of D-xylonate produced was reduced. To determine whether the
      co-factor NADP+ was limiting for D-xylonate production the Escherichia coli
      transhydrogenase encoded by udhA, the Bacillus subtilis glyceraldehyde 3
      phosphate dehydrogenase encoded by gapB or the S. cerevisiae glutamate
      dehydrogenase encoded by GDH2 was co-expressed with xyd1 in the parent and GRE3
      deficient strains. Although each of these enzymes enhanced NADPH consumption on D
      glucose, they did not enhance D-xylonate production, suggesting that NADP+ was
      not the main limitation in the current D-xylonate producing strains.

PMID- 20680265
TI  - Characterization of endo-1,3-1,4-beta-glucanases in GH family 12 from Magnaporthe
      oryzae.
AB  - We have cloned three putative endoglucanase cDNAs, designated MoCel12A, MoCel12B,
      and MoCel12C, from Magnaporthe oryzae. The deduced peptide sequences of both
      MoCel12A and MoCel12B contain secretion signal peptides and a catalytic core
      domain that classify them into GH subfamily 12-1. In contrast, the deduced
      peptide sequence of MoCel12C consists of a signal peptide, a catalytic core
      domain, and a fungal-type carbohydrate binding module belonging to GH subfamily
      12-2. Although most GH family 12 endoglucanases hydrolyze beta-1,4-glucans such
      as carboxymethylcellulose or phosphoric acid-swollen cellulose, MoCel12A that was
      prepared by overexpression in M. oryzae and Brevibacillus choshinensis hydrolyzed
      specifically 1,3-1,4-beta-glucans, such as barley beta-glucan and lichenan. The
      specific activity of MoCel12A overexpressed in M. oryzae was about 20 times
      higher than that prepared from B. choshinensis. Furthermore, MoCel12B prepared by
      overexpression in B. choshinensis also revealed preferential hydrolysis of endo
      1,3-1,4-beta-glucans with limited hydrolysis on carboxymethylcellulose. In
      comparison with MoCel12A, the activity of MoCel12B was more stable under alkaline
      conditions. Levels of mRNA encoding MoCel12A were constitutively high during
      infection and spore formation. The overexpression and disruption of the MoCel12A
      gene did not affect germination, appressorium formation, or invasion rate;
      however, M. oryzae overexpressing MoCel12A produced larger numbers of spores than
      the wild type or a mutant in which the MoCel12A gene was disrupted. These results
      suggest that MoCel12A functions in part to hydrolyze 1,3-1,4-beta-glucan during
      infection and spore formation.

PMID- 20680266
TI  - Antimicrobial properties of nitric oxide and its application in antimicrobial
      formulations and medical devices.
AB  - This review describes the antimicrobial properties of nitric oxide (NO) and its
      application as an antimicrobial agent in different formulations and medical
      devices. We depict the eukaryotic biosynthesis of NO and its physiologic
      functions as a cell messenger and as an antimicrobial agent of the cell-mediated
      immune response. We analyze the antimicrobial activity of NO and the eukaryotic
      protective mechanisms against NO for the purpose of delineating the therapeutic
      NO dosage range required for an efficacious and safe antimicrobial activity. We
      also examine the role of NO produced by virulent bacteria in lessening the
      efficacy of traditional antimicrobials. In addition, we discuss the efficacy of
      NO in the healing of infected wounds, describing different NO-producing devices
      by category, analyzing therapeutic levels, duration of NO production, as well as
      commercial considerations. Finally, we provide current and future prospects for
      the design and use of NO-producing devices.

PMID- 20680267
TI  - Noninvasive quantification of coronary endothelial function by SPECT imaging in
      children with a history of Kawasaki disease.
AB  - PURPOSE: The feasibility of coronary function estimation by single photon
      emission computed tomography (SPECT) has been recently demonstrated. The aim of
      this study was to apply SPECT imaging in patients with previous Kawasaki disease
      (KD) to assess the coronary functional status at long-term follow-up of the acute
      phase of the disease. METHODS: Sixteen children with a history of KD underwent
      99mTc-sestamibi imaging at rest and during the cold pressor test (CPT).
      Myocardial blood flow (MBF) was estimated by measuring first transit counts in
      the pulmonary artery and myocardial counts from SPECT images. Coronary
      endothelial function was expressed as the ratio of the CPT to rest MBF. RESULTS:
      Six KD patients without coronary artery lesions served as controls and ten with
      coronary artery aneurysms during the acute phase of the disease were separated
      into two groups: group 1 (n=4) with regressed and group 2 (n=6) with persistent
      aneurysm at follow-up. The estimated coronary endothelial function was higher in
      controls compared to patients with coronary artery aneurysms (2.5+/-0.3 vs 1.7+/
      0.7, p<0.05). A significant difference in coronary endothelial function among
      groups was found (F=5.21, p<0.02). Coronary endothelial function was higher in
      patients of group 1 than in those of group 2 (1.9+/-0.6 vs 1.4+/-0.7, p<0.02).
      CONCLUSION: SPECT may be applied as a noninvasive method for assessing coronary
      vascular function in children with a history of KD, demonstrating an impaired
      response to the CPT, an endothelial-dependent vasodilator stimulus. These
      findings reinforce the concept that coronary endothelial dysfunction may
      represent a long-term sequela of KD.

PMID- 20680268
TI  - Type 1 cannabinoid receptor mapping with [18F]MK-9470 PET in the rat brain after
      quinolinic acid lesion: a comparison to dopamine receptors and glucose
      metabolism.
AB  - PURPOSE: Several lines of evidence imply early alterations in metabolic,
      dopaminergic and endocannabinoid neurotransmission in Huntington's disease (HD).
      Using [18F]MK-9470 and small animal PET, we investigated cerebral changes in type
      1 cannabinoid (CB1) receptor binding in the quinolinic acid (QA) rat model of HD
      in relation to glucose metabolism, dopamine D2 receptor availability and
      amphetamine-induced turning behaviour. METHODS: Twenty-one Wistar rats (11 QA and
      10 shams) were investigated. Small animal PET acquisitions were conducted on a
      Focus 220 with approximately 18 MBq of [18F]MK-9470, [18F]FDG and
      [11C]raclopride. Relative glucose metabolism and parametric CB1 receptor and D2
      binding images were anatomically standardized to Paxinos space and analysed voxel
      wise using Statistical Parametric Mapping (SPM2). RESULTS: In the QA model,
      [18F]MK-9470 uptake, glucose metabolism and D2 receptor binding were reduced in
      the ipsilateral caudate-putamen by 7, 35 and 77%, respectively (all p<2.10(-5)),
      while an increase for these markers was observed on the contralateral side (>5%,
      all p<7.10(-4)). [18F]MK-9470 binding was also increased in the cerebellum
      (p=2.10(-5)), where it was inversely correlated to the number of ipsiversive
      turnings (p=7.10(-6)), suggesting that CB1 receptor upregulation in the
      cerebellum is related to a better functional outcome. Additionally, glucose
      metabolism was relatively increased in the contralateral hippocampus, thalamus
      and sensorimotor cortex (p=1.10(-6)). CONCLUSION: These data point to in vivo
      changes in endocannabinoid transmission, specifically for CB1 receptors in the QA
      model, with involvement of the caudate-putamen, but also distant regions of the
      motor circuitry, including the cerebellum. These data also indicate the
      occurrence of functional plasticity on metabolism, D2 and CB1 neurotransmission
      in the contralateral hemisphere.

PMID- 20680269
TI  - Therapy of thyroid carcinoma with the histone deacetylase inhibitor MS-275.
AB  - PURPOSE: Dysregulation of histone acetylation associated with an up-regulation of
      histone deacetylase (HDAC) activity is common in malignant tumours. Therefore,
      HDAC inhibitors were developed whose effects on proliferation and apoptosis have
      been shown in different tumour entities. Since non-iodide-concentrating thyroid
      carcinomas represent a therapeutic problem, this study addressed the effects of
      the HDAC inhibitor MS-275 on thyroid carcinoma cells. METHODS: After the
      antiproliferative effect of MS-275 had been proven in different human and rat
      thyroid carcinoma cell lines, FRO82-2, SW1736 and FTC133 cells were further
      investigated with respect to changes in apoptosis, cell cycle and metabolism by
      the annexin V/propidium iodide assay, FACS analysis and uptake experiments
      employing 3-O-methyl-D-(3H)glucose, fluoro-2-deoxy-D-glucose2 [5,6-(3)H] and 14C
      aminoisobutyric acid (AIB). The induction of iodide transport and gene expression
      were investigated in 125iodide uptake experiments and real-time polymerase chain
      reaction (PCR). RESULTS: MS-275 induced a concentration- and time-dependent
      inhibition of proliferation in the thyroid carcinoma cell lines with varying IC50
      values. In FRO82-2, SW1736 and FTC133 cells characterized by low, moderate and
      high sensitivity an up-regulation of p21CIP/WAF1 expression and G1 and/or G2
      phase arrest were observed upon MS-275 exposure corresponding to the sensitivity
      of individual cell lines. In addition, high MS-275 concentrations increased the
      apoptotic cell fraction of FTC133 and SW1736 cells, whereas resistance to
      apoptosis and simultaneous up-regulation of Bcl-2 gene expression were observed
      in FRO82-2 cells. MS-275 treatment also mediated a concentration-dependent
      decrease of 3H-FDG uptake and an increased 3-O-methyl-D-(3H)glucose uptake in all
      thyroid carcinoma cell lines after 24 h, an increased uptake of both tracers in
      FTC133 cells after 48 h, and restored the functional activity of the sodium
      iodide symporter in SW1736 and FTC133 cells up to 20- and 45-fold. CONCLUSION: MS
      275 exerts dose-dependent antiproliferative effects including growth arrest,
      differentiation and apoptosis in some thyroid carcinoma cell lines and might,
      therefore, be considered for the treatment of anaplastic and non-iodide
      concentrating thyroid carcinomas.

PMID- 20680270
TI  - PET/CT-guided biopsies of metabolically active bone lesions: applications and
      clinical impact.
AB  - PURPOSE: In a minority of cases a definite diagnosis and stage grouping in cancer
      patients is not possible based on the imaging information of PET/CT. We report
      our experience with percutaneous PET/CT-guided bone biopsies to histologically
      verify the aetiology of hypermetabolic bone lesions. METHODS: We retrospectively
      reviewed the data of 20 consecutive patients who underwent multimodal image
      guided bone biopsies using a dedicated PET/CT system in a step-by-step technique.
      Technical and clinical success rates of PET/CT-guided biopsies were evaluated.
      Questionnaires were sent to the referring physicians to assess the impact of
      biopsies on patient management and to check the clinical need for PET/CT-guided
      biopsies. RESULTS: Clinical indications for biopsy were to histologically verify
      the aetiology of metabolically active bone lesions without a morphological
      correlate confirming the suspicion of metastases in 15 patients, to determine the
      origin of suspected metastases in 3 patients and to evaluate the appropriateness
      of targeted therapy options in 2 patients. Biopsies were technically successful
      in all patients. In 19 of 20 patients a definite histological diagnosis was
      possible. No complications or adverse effects occurred. The result of PET/CT
      guided bone biopsies determined a change of the planned treatment in overall 56%
      of patients, with intramodality changes, e.g. chemotherapy with palliative
      instead of curative intent, and intermodality changes, e.g. systemic therapy
      instead of surgery, in 22 and 50%, respectively. CONCLUSION: PET/CT-guided bone
      biopsies are a promising alternative to conventional techniques to make
      metabolically active bone lesions-especially without a distinctive morphological
      correlate-accessible for histological verification. PET/CT-guided biopsies had a
      major clinical impact in patients who otherwise cannot be reliably stage grouped
      at the time of treatment decisions.

PMID- 20680271
TI  - Allogeneic natural killer cells for refractory lymphoma.
AB  - We reported that IL-2 activated autologous NK cells can induce, but not maintain
      durable remissions in lymphoma patients. We hypothesized that allogeneic NK cells
      may overcome class I MHC-mediated inhibition of NK cell killing. In a pilot
      study, we evaluated infusion of haploidentical donor NK cells for antitumor
      efficacy. Six patients with advanced B cell non-Hodgkin lymphoma (NHL) received
      rituximab, cyclophosphamide, and fludarabine as immunosupression to permit
      homeostatic NK cell expansion, followed by CD3-depleted NK cell-enriched cell
      products followed by subcutaneous IL-2 administration (10 x 10(6) units every
      other day x 6 doses). At 2 months, four patients showed an objective clinical
      response. We observed early donor cell persistence in two patients (blood and in
      tumor-bearing node), but this was not detectable beyond 7 days. All patients
      demonstrated substantial increases in host-regulatory T cells (Treg) after NK
      cell and IL-2 therapy (180 +/- 80 cells/microl vs. baseline: 58 +/- 24
      cells/microl, p = 0.04) which may have limited donor cell expansion in vivo.
      These findings suggest safety and feasibility of allogeneic NK cell therapy in
      patients with lymphoma; however host Treg and inadequate immunodepletion may
      contribute to a hostile milieu for NK cell survival and expansion. Cell therapy
      trials should incorporate novel strategies to limit Treg expansion.

PMID- 20680272
TI  - Comparison between radial head replacement and open reduction and internal
      fixation in clinical treatment of unstable, multi-fragmented radial head
      fractures.
AB  - The objective of this study was to compare replacement of the radial head by
      metal prostheses with open reduction and internal fixation (ORIF) for the
      treatment of unstable, multi-fragmented radial head fractures. A prospective
      randomised controlled trial was employed to investigate 45 patients with
      unstable, multi-fragmented fractures of the radial head, from January 2004 to
      June 2007. The patients were randomised to two groups: the ORIF group and the
      radial head replacement group. Over the next two years, follow-up assessments
      recorded Broberg and Morrey scores and postoperative complication rate.
      Statistical analysis was performed. According to Broberg and Morrey scores,
      patients receiving radial head replacement achieved significantly better clinical
      results with 91% (20/22) good or excellent compared to patients assigned to the
      ORIF group with 65.2% (15/23) good or excellent results (P < 0.01). Postoperative
      complication rate of the radial head replacement group (13.6%) was significantly
      lower than that of the ORIF group (47.9%; P < 0.01). Compared with open reduction
      and internal fixation, radial head replacement with a metal prostheses resulted
      in favourable joint function for the unstable, multi-fragmented fractures of the
      radial head.

PMID- 20680273
TI  - The management of nonunion and delayed union of patella fractures: a systematic
      review of the literature.
AB  - Nonunion and delayed union of patella fractures are rare conditions that are
      fraught with challenges. There exists limited evidence in the literature to guide
      the clinician in the management of these complications. Therefore, the purpose of
      this study was to perform a systematic review of the available evidence on the
      management of nonunion and delayed union of patella fractures. A total of five
      publications which met our criteria were identified and formed the basis of this
      study. The decision making in the treatment of this condition is based on the
      functional demands of the patient, the factors that led to the development of the
      nonunion, the potential impact of the biomechanical effects of a total
      patellectomy, and the presence of an intact extensor mechanism of the knee for a
      later reconstructive procedure. Patients with low functional demands may be
      managed with nonoperative methods; however, those who perform heavy physical work
      or participate in sports usually require open reduction and internal fixation.
      Tension band wiring is the treatment of choice for patients suitable for a
      reconstructive procedure. Partial or total patellectomy is also an option for
      small distal fragments or an inability to satisfactorily perform internal
      fixation.

PMID- 20680274
TI  - Vascularised fibular graft for the treatment of congenital pseudarthrosis of the
      tibia: long-term complications in the donor leg.
AB  - Treatment of congenital pseudarthrosis of the tibia is still controversial, and
      vascularised fibula graft is a reliable method for consolidation, although
      complications can occur in the donor leg after fibula grafting. This study
      evaluates 16 patients with congenital pseudarthrosis of the tibia (CPT) treated
      with contralateral fibular graft, with regard to complications in the donor leg,
      and assesses the influence of distal tibiofibular joint arthrodesis in these
      complications. All patients with CPT were consecutively submitted to surgical
      treatment with contralateral fibular graft. The mean follow-up was 94 months,
      varying from 44 to 162 months. The long-term effects in the donor leg were
      determined, and 12 cases with distal tibiofibular arthrodesis (group 1) were
      compared with a group without arthrodesis (group 2). Half of the patients had
      proximal migration of the lateral malleolus. Eight patients had ankle valgus.
      Group 1 had an average valgus tilt angle of 5.8 degrees , while group 2 had an
      average angle of 1.5 degrees . There was no significant difference between the
      patients with or without distal tibiofibular joint arthrodesis. The patients with
      a distal fibula remnant smaller than 5 cm had greater valgus tilt angle
      measurements. Distal tibiofibular arthrodesis was not effective in preventing all
      the complications in the donor leg; however, it can lessen the severity of the
      complications. Our results show that a distal fibular remnant greater than 5 cm
      should be retained to prevent ankle valgus.

PMID- 20680275
TI  - Rupture of the long head biceps tendon treated with tenodesis to the coracoid
      process. Results at more than 30 years.
AB  - We evaluated patients at very long term with rupture of the long head biceps
      tendon (LHBT) in whom the tendon stump had been sutured to the coracoid tip
      (Gilcreest technique). Our aim was to determine the natural history of shoulders
      deprived of the LHBT and to assess the validity of the surgical technique.
      Between 1969 and 1981, 30 patients with rupture of the LHBT and no evidence of
      cuff tear underwent the Gilcreest operation. The mean age of the patients was 32
      years (range, 20-49). Six of them were professional gymnasts. The 28 patients
      that could be traced were evaluated a mean of 31 years after operation. The mean
      Constant score (CS) was 74 in the entire group, and 86 in 22. The latter patients
      complained occasionally of mild shoulder pain. The remaining six patients had a
      mean CS of 56 (range, 40-81). Of the six, four (aged 66-71 years) had clinical
      and MR evidence of rotator cuff tear. The other two had undergone arthroscopic
      cuff repair (CS, 75-81). After operation, all professional gymnasts had returned
      to sport activity and all the other patients had resumed their jobs. After 30
      years, the majority of the patients who had undergone the Gilcreest operation had
      good functional and cosmetic outcomes. Only a few patients had a cuff tear. The
      role of the LHBT as depressor of the humeral head is probably less important than
      generally believed.

PMID- 20680276
TI  - Conservative versus surgical management of Pipkin type I fractures associated
      with posterior dislocation of the hip: a randomised controlled trial.
AB  - The aim of this study was to evaluate the long-term results of conservative and
      surgical fragment excision treatment in patients with Pipkin type 1 fractures of
      the femoral head associated with posterior dislocation of the hip by a randomised
      controlled trial. Sixteen patients were randomly divided into two groups: the
      conservative group was treated by closed reduction, and the surgical group was
      treated by closed reduction followed with fragment excision. Functional outcome
      was determined using the Thompson and Epstein score and the Merle d'Aubigne and
      Postel score. Outcome of the conservative group was worse than that of the
      surgical group (p = 0.032). The randomised controlled trial proves surgical
      fragment excision after closed reduction is an effective treatment for Pipkin
      type 1 fractures.

PMID- 20680277
TI  - Rapamycin suppresses ROS-dependent apoptosis caused by selenomethionine in A549
      lung carcinoma cells.
AB  - PURPOSE: Although selenium compounds possess chemotherapeutic features by
      inducing apoptosis in cancer cells with trivial side effects on normal cells, the
      mechanisms underlying its anti-cancer activity are insufficiently understood at
      the present. In this study, we investigated the effects of rapamycin on apoptosis
      induced by seleno-L-methionine (SeMet) or selenite in A549 cells. METHODS: The
      effects of Se compounds, SeMet and selenite, on cell proliferation, apoptosis and
      its signaling pathway were investigated in established human adenocarcinoma cell
      line (A549). Cancer cells were treated with each Se during different periods.
      Cell apoptosis and signaling molecules were analyzed by flow cytometry (TUNEL
      method) or immunoblotting, respectively. RESULTS: SeMet induces reactive oxygen
      species generation associated with the induction of apoptosis, because
      pretreatment of cells with N-acetyl-L-cysteine completely blocked SeMet-induced
      apoptosis. We also found that rapamycin completely suppressed the apoptosis of
      cells treated by SeMet, but not selenite. SeMet-induced apoptosis is
      significantly downregulated in combination with PI3 K family inhibitors
      (LY294002, wortmannin, PI-103, and 3-methyladenine). In addition, ROS generation
      was included in downstream signaling events associated with the phosphorylation
      of mTOR, because pretreatment of cells with rapamycin inhibited ROS generation.
      CONCLUSION: These results suggest that SeMet-induced apoptosis is affected by the
      Akt/mTOR/ROS pathway in A549 cells. Akt serves an anti-survival function in the
      system of SeMet-treated lung cancer cells, but autophagic signaling remained
      unsolved.

PMID- 20680278
TI  - Effects of methimazole on the elimination of irinotecan.
AB  - PURPOSE: To study the possible pharmacokinetic and pharmacodynamic interactions
      between irinotecan and methimazole. METHODS: A patient treated for colorectal
      cancer with single agent irinotecan received methimazole co-medication for
      Graves' disease. Irinotecan pharmacokinetics and side effects were followed
      during a total of four courses (two courses with and two courses without
      methimazole). RESULTS: Plasma concentrations of the active irinotecan metabolite
      SN-38 and its inactive metabolite SN-38-Glucuronide were both higher (a mean
      increase of 14 and 67%, respectively) with methimazole co-medication, compared to
      irinotecan monotherapy. As a result, the mean SN-38 glucuronidation rate
      increased with 47% during concurrent treatment. Other possible confounding
      factors did not change over time. Specific adverse events due to methimazole co
      treatment were not seen. CONCLUSIONS: Additional in vitro experiments suggest
      that these results can be explained by induction of UGT1A1 by methimazole,
      leading to higher SN-38G concentrations. The prescribed combination of these
      drugs may lead to highly toxic intestinal SN-38 levels. We therefore advise
      physicians to be very careful in combining methimazole with regular irinotecan
      doses, especially in patients who are prone to irinotecan toxicity.

PMID- 20680279
TI  - Identification of differentially expressed genes in Flammulina velutipes with
      anti-tyrosinase activity.
AB  - It was previously shown that fruiting bodies of the mushroom, Flammulina
      velutipes, exert anti-tyrosinase activity by producing a triacylglycerol
      characterized as 1',3'-dilinolenoyl-2'-linoleoylglycerol (LnLLn). In this study,
      we provide evidence that the mycelia of F. velutipes grown on glucose, but not on
      glycerol, exhibit anti-tyrosinase activity. To identify genes possibly involved
      in the process of expressing anti-tyrosinase activity in F. velutipes, a reverse
      transcription-polymerase chain reaction (RT-PCR) method that involves annealing
      control primers (ACPs) was employed. Using 120 ACPs, a total of 84 differentially
      expressed genes (DEGs) in F. velutipes mycelia with anti-tyrosinase activity were
      cloned and sequenced. Basic Local Alignment Search Tool (BLAST) searches revealed
      that 72 of the genes have known sequence homology. Of these, three genes involved
      in the synthesis and modification of fatty acids were selected and further
      quantified by real-time RT-PCR. These genes involved in fatty acid-biosynthetic
      processes can be potential candidates for further studies related to the
      development of a new anti-browning agent.

PMID- 20680280
TI  - The effect of rhamnolipid biosurfactant produced by Pseudomonas fluorescens on
      model bacterial strains and isolates from industrial wastewater.
AB  - In this study, the effect of rhamnolipid biosurfactant produced by Pseudomonas
      fluorescens on bacterial strains, laboratory strains, and isolates from
      industrial wastewater was investigated. It was shown that biosurfactant,
      depending on the concentration, has a neutral or detrimental effect on the growth
      and protein release of model Gram (+) strain Bacillus subtilis 168. The growth
      and protein release of model Gram (-) strain Pseudomonas aeruginosa 1390 was not
      influenced by the presence of biosurfactant in the medium. Rhamnolipid
      biosurfactant at the used concentrations supported the growth of some slow
      growing on hexadecane bacterial isolates, members of the microbial community.
      Changes in cell surface hydrophobicity and permeability of some Gram (+) and Gram
      (-) isolates in the presence of rhamnolipid biosurfactant were followed in
      experiments in vitro. It was found that bacterial cells treated with
      biosurfactant became more or less hydrophobic than untreated cells depending on
      individual characteristics and abilities of the strains. For all treated strains,
      an increase in the amount of released protein was observed with increasing the
      amount of biosurfactant, probably due to increased cell permeability as a result
      of changes in the organization of cell surface structures. The results obtained
      could contribute to clarify the relationships between members of the microbial
      community as well as suggest the efficiency of surface properties of rhamnolipid
      biosurfactant from Pseudomonas fluorescens making it potentially applicable in
      bioremediation of hydrocarbon-polluted environments.

PMID- 20680281
TI  - Short-term UV-B and UV-C radiations preferentially decrease spermidine contents
      and arginine decarboxylase transcript levels of Synechocystis sp. PCC 6803.
AB  - To investigate the short term effect of ultraviolet (UV) radiations on changes in
      pigments and polyamine contents, Synechocystis sp. PCC 6803 cells after exposure
      to UV-radiation were extracted by dimethylformamide and perchloric acid for
      pigments and polyamines determination, respectively. Cell growth was slightly
      decreased after 1 h exposure to UV-A and UV-B radiations. UV-C had little effect
      on cell growth despite the decrease of photosynthetic rate by about 18%. UV-A and
      UV-B decreased the contents of chlorophyll a and carotenoids whereas UV-C
      decreased chlorophyll a but had no effect on carotenoids. Spermidine contents
      were unaffected by UV-A, in contrast to the reduction of 25 and 50% by UV-B and
      UV-C, respectively. All three types of UV-radiation particularly reduced
      perchloric acid-insoluble spermidine. Importantly, putrescine and spermine which
      accounted for less than 1% of intracellular polyamines were increased by about
      three- to eight-fold by UV-B and UV-C, respectively. The changes in polyamines
      contents by UV-B and UV-C were consistent with the changes in transcript levels
      of arginine decarboxylase mRNA, but not with the protein levels. The decrease in
      the transcripts of adc2 but not adc1 was observed with UV-B and UV-C treatments.

PMID- 20680282
TI  - Comparison and characterization of microbial communities in sulfide-rich
      wastewater with and without propidium monoazide treatment.
AB  - A 16S rRNA gene-based culture-independent approach was used to study the
      bacterial and archaeal communities in a sulfide-rich wastewater. Propidium
      Monoazide (PMA) treatment was applied to limit the analysis to the fraction of
      viable cells in environment. A total of 104 and 68 clones respective from
      bacterial clone library and archaeal library were picked and analyzed by
      restriction fragment length polymorphism (RFLP). 35 RFLP patterns from bacterial
      clone library and 10 RFLP patterns from archaeal clone library were unique and
      the respective clones were selected for sequencing. BLAST analysis and RFLP
      analysis showed that the bacterial clone library mainly consisted of
      Gammaproteobacteria (73%), Anaerolineae (6%), Bacilli (5%), Deltaproteobacteria
      (7%), Clostridia (4%), Bacteroidetes (1%), and Chlorobia (1%); Methanomicrobia
      (99%) and Thermococci (1%) were the only two lineages of the archaeal domains.
      This study gave a first insight into the overall microbial structure in a cloth
      printing and dyeing wastewater treatment plant with high concentration of sulfide
      and increased knowledge on the applicability of the PMA treatment in combination
      with PCR-based molecular techniques to analyze only viable cells in microbial
      ecology.

PMID- 20680283
TI  - Down-regulated expression of IKZF1 mRNA in peripheral blood mononuclear cells
      from patients with systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease with
      complex genetic inheritance. IKZF1 was established as a new susceptibility gene
      for SLE in a recent genome-wide association study (GWAS) in Chinese Han
      population. In order to examine whether expression levels of IKZF1 contribute to
      the pathogenesis of SLE, we estimated IKZF1 mRNA expression levels in peripheral
      blood mononuclear cells (PBMCs) via fluorescent quantitative reverse
      transcription polymerase chain reaction (RT-PCR) in 60 patients with SLE and 60
      controls. We also explored whether the IKZF1 mRNA expression levels are
      associated with the variant of the SNP rs4917014 and the SLE Disease Activity
      Index (SLEDAI). The expression levels of IKZF1 mRNA in patients with SLE were
      significantly decreased compared with those in healthy controls (P<0.001). No
      significant differences were found between IKZF1 mRNA expression levels and
      SLEDAI scores, SNP rs4917014. Our results suggest that decreased expression of
      IKZF1 mRNA may be correlated with the pathogenesis of SLE.

PMID- 20680284
TI  - Disability of Arm Shoulder and Hand Questionnaire in rheumatoid arthritis
      patients: relationship with disease activity, HAQ, SF-36.
AB  - Rheumatoid arthritis (RA) is a systemic disease that causes disability.
      Disability and quality of life indexes are used in the assessment and treatment
      of patients with RA. Disability of Arm, Shoulder and Hand Questionnaire (DASH) is
      a patient-based outcome measurement developed to evaluate the upper extremities.
      The aim of this study was to investigate the clinical relevance of DASH in RA
      patients and the relationship between disease activity and health-related quality
      of life measurements. One hundred and sixty-six RA patients were included in the
      study. Disease activity was measured with Disease Activity Score 28 (DAS28),
      Simplified Disease Activity Index (SDAI), and Clinical Disease Activity Index
      (CDAI). The DASH questionnaire, Short-Form 36 (SF-36), and Health Assessment
      Questionnaire (HAQ) were completed by all patients. The DASH score moderately
      correlated with DAS28 (r=0.672), SDAI (r=0.586) and CDAI (r=0.565). When the
      patients were grouped according to the activity obtained using the three disease
      activity measurements, DASH score was statistically significantly higher with
      higher disease activity (P<0.001). A high correlation (r=0.883) was found between
      DASH and HAQ (r=0.883). The SF-36 scores were correlated with DASH (r=-0.785 with
      physical component, r=-0.619 with mental component). DASH scores correlate with
      disease activity indices, functional disability and QoL and can be used in the
      assessment of upper extremities in patients with RA.

PMID- 20680285
TI  - Theory-based analysis of anti-inflammatory effect of infliximab on Crohn's
      disease and rheumatoid arthritis.
AB  - In Japan, the recommended dosage regimens of infliximab (IFX) for treatment of
      rheumatoid arthritis (RA) and Crohn's disease (CD) are different. However, the
      differences have not been analyzed theoretically. In a previous study, we
      constructed a pharmacokinetic-pharmacodynamic model to investigate the effects of
      IFX for CD and found it useful to establish a rational dosage regimen of IFX for
      individual patients with CD. In the present study, we investigated whether the
      theory-based model could be used for cases of RA and also used it to evaluate the
      validity of the dosage regimen. The results obtained with our model were in good
      agreement with observed tender joint count (TJC) ratio data, which was considered
      to show the validity of our analysis. Thus, we concluded that the model could be
      used for patients with RA. Furthermore, a second administration of IFX given 2
      weeks after the first infusion was important to achieve remission in the early
      stage of RA. We also compared the estimated pharmacodynamic parameters of RA with
      those of CD. The elimination rate constant of inflammation in RA was greater than
      that in CD, suggesting that the recovery from inflammation in RA is faster than
      that in CD, and indicating a reason for the difference in dosage between RA and
      CD. In conclusion, use of our model in light of the individual quantitative
      factor of tumor necrosis factor (TNF)-alpha allows establishment of IFX dosage
      regimens for individual patients.

PMID- 20680286
TI  - Four-dimensional computed tomography: a method of assessing right ventricular
      outflow tract and pulmonary artery deformations throughout the cardiac cycle.
AB  - OBJECTIVE: To characterise 3D deformations of the right ventricular outflow tract
      (RVOT)/pulmonary arteries (PAs) during the cardiac cycle and estimate the errors
      of conventional 2D assessments. METHODS: Contrast-enhanced, ECG-gated
      cardiovascular computed tomography (CT) findings were retrospectively analysed
      from 12 patients. The acquisition of 3D images over 10 phases of the cardiac
      cycle created a four-dimensional CT (4DCT) dataset. The datasets were
      reconstructed and deformation measured at various levels of the RVOT/PAs in both
      space and time. Section planes were either static or dynamic relative to the
      motion of the structures. RESULTS: 4DCT enabled measurement and characterisation
      of in vivo 3D changes of patients' RVOT/PA during the cardiac cycle. The studied
      patient population showed a wide range of RVOT/PA morphologies, sizes and
      dynamics that develop late after surgical repair of congenital heart disease.
      There were also significant differences in the measured cross-sectional areas of
      the structures between static and dynamic section planes (up to 150%, p<0.05)
      secondary to large 3D displacements and rotations. CONCLUSIONS: 4DCT imaging data
      suggest high variability in RVOT/PA dynamics and significant errors in
      deformation measurements if 3D analysis is not carried out. These findings play
      an important role for the development of novel percutaneous approaches to
      pulmonary valve intervention.

PMID- 20680287
TI  - Diffusion-weighted echo planar imaging in patients with recent myocardial
      infarction.
AB  - OBJECTIVE: To evaluate a diffusion-weighted (DW) black blood MR sequence for the
      detection of myocardium signal abnormalities in patients with recent myocardial
      infarction (MI). METHODS: A DW black blood EPI sequence was acquired at 1.5 T in
      12 patients with recent MI. One slice per patient was acquired with b=0 and b=50
      s/mm2. A standard short tau inversion recovery (STIR) T2-weighted sequence was
      acquired at the same level. Viability was assessed with delayed-enhancement
      sequences. Images were analyzed qualitatively and quantitatively. A non
      parametric Wilcoxon test was used for statistical analysis, with a significance
      level of P<.05. RESULTS: The mean quality of blood suppression was higher on DW
      EPI images than on STIR T2-weighted images (3.9+/-0.3 and 3.0+/-0.7,
      respectively; P=0.01). Myocardial high signal areas were detected in respectively
      100% (12/12) and 67% (8/12) of the patients on DW EPI and STIR T2-weighted
      images. The four patients (33%) with false-negative STIR T2 findings all had high
      signal areas on DW EPI images corresponding to the location of the MI on the
      delayed-enhanced images. CONCLUSION: DW EPI sequences are a feasible alternative
      to standard STIR T2-weighted sequences for detecting myocardium high signal areas
      in patients with recent MI.

PMID- 20680288
TI  - Effect on renal function of an iso-osmolar contrast agent in patients with
      monoclonal gammopathies.
AB  - OBJECTIVE: To assess the safety of the non-ionic iso-osmolar contrast agent
      iodixanol on renal function in patients with monoclonal gammopathies undergoing
      CT. METHODS: We explored the effect of iodixanol on renal function in 30 patients
      with monoclonal gammopathies and 20 oncological patients with a normal
      electrophoretic profile (control group). The parameters used to estimate renal
      function were: serum creatinine, eGFR (determined 24 h before and 48 h after the
      administration of iodixanol), and urinary excretion of Neutrophil Gelatinase
      Associated Lipocalin (NGAL) determined 2 h and 24 h after. Serum creatinine was
      also determined 1 month after the administration of iodixanol. RESULTS: No
      significant increase in serum creatinine values were observed in the monoclonal
      gammopathies group and in 19/20 patients in the control group. Only 1 patient in
      the control group developed a transient contrast agent-induced nephropathy. We
      found no statistically significant difference between the two groups regarding
      the percentage variation from baseline values of serum creatinine, creatinine
      clearance, NGAL 2 h after, and eGFR. Whereas NGAL at 24 h showed a statistically
      significant increase in patients with Monoclonal gammopathies. CONCLUSION: The
      use of iodixanol appears to be safe in patients with monoclonal gammopathies and
      an eGFR>= 60 ml/min/1.73 mq.

PMID- 20680289
TI  - The diagnostic accuracy of US, CT, MRI and 1H-MRS for the evaluation of hepatic
      steatosis compared with liver biopsy: a meta-analysis.
AB  - OBJECTIVE: To meta-analyse the diagnostic accuracy of US, CT, MRI and 1H-MRS for
      the evaluation of hepatic steatosis. METHODS: From a comprehensive literature
      search in MEDLINE, EMBASE, CINAHL and Cochrane (up to November 2009), articles
      were selected that investigated the diagnostic performance imaging techniques for
      evaluating hepatic steatosis with histopathology as the reference standard. Cut
      off values for the presence of steatosis on liver biopsy were subdivided into
      four groups: (1) >0, >2 and >5% steatosis; (2) >10, >15 and >20%; (3) >25, >30
      and >33%; (4) >50, >60 and >66%. Per group, summary estimates for sensitivity and
      specificity were calculated. The natural-logarithm of the diagnostic odds ratio
      (lnDOR) was used as a single indicator of test performance. RESULTS: 46 articles
      were included. Mean sensitivity estimates for subgroups were 73.3-90.5% (US),
      46.1-72.0% (CT), 82.0-97.4% (MRI) and 72.7-88.5% (1H-MRS). Mean specificity
      ranges were 69.6-85.2% (US), 88.1-94.6% (CT), 76.1-95.3% (MRI) and 92.0-95.7% (1H
      MRS). Overall performance (lnDOR) of MRI and 1H-MRS was better than that for US
      and CT for all subgroups, with significant differences in groups 1 and 2.
      CONCLUSION: MRI and 1H-MRS can be considered techniques of choice for accurate
      evaluation of hepatic steatosis.

PMID- 20680290
TI  - Evaluation of computer-aided detection and dual energy software in detection of
      peripheral pulmonary embolism on dual-energy pulmonary CT angiography.
AB  - PURPOSE: To evaluate the sensitivity of computer-aided detection(CAD) and dual
      energy software('Lung PBV', 'Lung Vessels') for detecting peripheral pulmonary
      embolism(PE). MATERIALS AND METHODS: Between Jan-2007 and Jan-2008, 309 patients
      underwent dual-energy CT angiography(DECTA) for the evaluation of suspected PE.
      Among them, 37 patients were retrospectively selected; 21 with PE at segmental-or
      below levels and 16 without PE according to clinical reports. A standard computer
      assisted detection (CAD) package and two new types of software('Lung PBV', 'Lung
      Vessels') were applied on a dedicated workstation. This resulted in four
      alternative tests for detecting PE: DECTA alone and DECTA with CAD, 'Lung
      Vessels' and 'Lung PBV'. Two radiologists independently read all cases at
      different reading sessions. Two thoracic radiologists set the reference standard
      by combining all information from DECTA and software. The sensitivity of
      detection for all, segmental and subsegmental-or-below PE were assessed. RESULTS:
      The reference standard contained 136 PE(segmental 65, subsegmental-or-below 71).
      With DECTA alone, the sensitivity of detection for all, segmental and
      subsegmental-or-below pulmonary arteries was 54.5%/73.7%/34.4%; DECTA with CAD,
      57.8%/76.8%/37.9%; DECTA with 'Lung PBV', 61.1%/79.9%/41.4%; DECTA with 'Lung
      Vessels', 64.0%/78.3%/48.5% respectively. CONCLUSION: The use of CAD, Lung
      Vessels and Lung PBV shows improved capability to detect peripheral PE.

PMID- 20680291
TI  - Tumour thickness in oral cancer using an intra-oral ultrasound probe.
AB  - OBJECTIVES: To investigate tumour-thickness measurement with an intra-operative
      ultrasound (US) probe. METHODS: A retrospective data analysis was undertaken for
      a total of 65 patients with a T1-2 oral cavity cancer, who were seen at a
      tertiary referral centre between 2004 and 2010. The correspondence between tumour
      thickness measured by ultrasonography and histopathology was assessed by
      Pearson's correlation coefficient, and also between tumour thickness and the
      development of neck metastasis. RESULTS: In 11 cases, intra-oral measurement was
      not optimal due to limited mouth opening (n=2) or impossibility to depict the
      lesion (n=9). Tumour thickness measured by US correlated well with histopathology
      (n=23, R=0.93). Tumour thickness of <=7 mm carries a risk of lymph node
      metastasis of 12%, whereas in tumours exceeding 7 mm this risk is 57% (p=0.001).
      Twenty-five percent developed neck metastasis and 19% had local recurrence.
      CONCLUSION: Tumour thickness is an important predictive marker for lymph node
      metastases. As such, it can help in decision-making with regard to management of
      the primary tumour and neck. Based upon our findings, a wait-and-see policy is
      only warranted for superficial lesions with tumour thickness of less than 7 mm,
      but only if regular follow-up using US-guided aspiration of the neck is ensured.

PMID- 20680292
TI  - Athletic injuries of the extensor carpi ulnaris subsheath: MRI findings and
      utility of gadolinium-enhanced fat-saturated T1-weighted sequences with wrist
      pronation and supination.
AB  - OBJECTIVE: To report the magnetic resonance imaging (MRI) findings in athletic
      injuries of the extensor carpi ulnaris (ECU) subsheath, assessing the utility of
      gadolinium-enhanced (Gd) fat-saturated (FS) T1-weighted sequences with wrist
      pronation and supination. METHODS: Sixteen patients (13 male, three female; mean
      age 30.3 years) with athletic injuries of the ECU subsheath sustained between
      January 2003 and June 2009 were included in this retrospective study. Initial and
      follow-up 1.5-T wrist MRIs were performed with transverse T1-weighted and STIR
      sequences in pronation, and Gd FS T1-weighted sequences with wrist pronation and
      supination. Two radiologists assessed the type of injury (A to C), ECU tendon
      stability, associated lesions and rated pulse sequences using a three-point
      scale: 1=poor, 2=good and 3=excellent. RESULTS: Gd-enhanced FS T1-weighted
      transverse sequences in supination (2.63) and pronation (2.56) were most
      valuable, compared with STIR (2.19) and T1-weighted (1.94). Nine type A, one type
      B and six type C injuries were found. There were trends towards diminution in
      size, signal intensity and enhancement of associated pouches on follow-up MRI and
      tendon stabilisation within the ulnar groove. CONCLUSION: Gd-enhanced FS T1
      weighted sequences with wrist pronation and supination are most valuable in
      assessing and follow-up athletic injuries of the ECU subsheath on 1.5-T MRI.

PMID- 20680293
TI  - Prospective comparison of T2w-MRI and dynamic-contrast-enhanced MRI, 3D-MR
      spectroscopic imaging or diffusion-weighted MRI in repeat TRUS-guided biopsies.
AB  - OBJECTIVES: To compare T2-weighted MRI and functional MRI techniques in guiding
      repeat prostate biopsies. METHODS: Sixty-eight patients with a history of
      negative biopsies, negative digital rectal examination and elevated PSA were
      imaged before repeat biopsies. Dichotomous criteria were used with visual
      validation of T2-weighted MRI, dynamic contrast-enhanced MRI and literature
      derived cut-offs for 3D-spectroscopy MRI (choline-creatine-to-citrate ratio
      >0.86) and diffusion-weighted imaging (ADC * 10(3) mm(2)/s < 1.24). For each
      segment and MRI technique, results were rendered as being suspicious/non
      suspicious for malignancy. Sextant biopsies, transition zone biopsies and at
      least two additional biopsies of suspicious areas were taken. RESULTS: In the
      peripheral zones, 105/408 segments and in the transition zones 19/136 segments
      were suspicious according to at least one MRI technique. A total of 28/68 (41.2%)
      patients were found to have cancer. Diffusion-weighted imaging exhibited the
      highest positive predictive value (0.52) compared with T2-weighted MRI (0.29),
      dynamic contrast-enhanced MRI (0.33) and 3D-spectroscopy MRI (0.25). Logistic
      regression showed the probability of cancer in a segment increasing 12-fold when
      T2-weighted and diffusion-weighted imaging MRI were both suspicious (63.4%)
      compared with both being non-suspicious (5.2%). CONCLUSION: The proposed system
      of analysis and reporting could prove clinically relevant in the decision whether
      to repeat targeted biopsies.

PMID- 20680294
TI  - Contemporary outcomes of focal therapy in prostate cancer: what do we know so
      far...
AB  - INTRODUCTION: Despite the enthusiasm for an organ preserving approach to prostate
      cancer treatment, studies that support the supposition that this approach will
      offer patients the "Trifecta" of prostate cancer therapy are lacking. METHODS:
      Review of published peer review literature using a combination of the terms
      "Focal", "Prostate Cancer", "Therapy", "Cryoablation", "HIFU", and "Clinical
      Trial". RESULTS: To date only three prospective clinical trials of subtotal
      prostate cryoablation and one of subtotal high-intensity focused ultrasound
      (HIFU) have been reported along with one retrospective review of patients treated
      in a subtotal manner with cryotherapy. In total, these reports present only 166
      patients. All current strategies for focally ablative therapy for prostate cancer
      treatment have varied in their eligibility criteria and in the amount of tissue
      targeted for destruction and/or preservation. CONCLUSIONS: Very little is
      published on either the oncologic outcomes or quality-of-life outcomes following
      subtotal prostate ablation to justify its growing popularity with both patients
      and physicians. Significant research and clinical trials that examine patient
      selection, biopsy strategies, and ablative energies, along with oncologic
      efficacy and quality-of-life outcomes are needed. This article will review the
      current state of knowledge regarding subtotal prostate ablative strategies.

PMID- 20680295
TI  - Torpor patterns, arousal rates, and temporal organization of torpor entry in
      wildtype and UCP1-ablated mice.
AB  - In eutherian mammals, uncoupling protein 1 (UCP1) mediated non-shivering
      thermogenesis from brown adipose tissue (BAT) provides a mechanism through which
      arousal from torpor and hibernation is facilitated. In order to directly assess
      the magnitude by which the presence or absence of UCP1 affects torpor patterns,
      rewarming and arousal rates within one species we compared fasting induced torpor
      in wildtype (UCP1(+/+)) and UCP1-ablated mice (UCP(-/-)). Torpor was induced by
      depriving mice of food for up to 48 h and by a reduction of ambient temperature
      (T (a)) from 30 to 18 degrees C at four different time points after 18, 24, 30
      and 36 h of food deprivation. In most cases, torpor bouts occurred within 20 min
      after the switch in ambient temperature (30-18 degrees C). Torpor bouts expressed
      during the light phase lasted 3-6 h while significantly longer bouts (up to 16 h)
      were observed when mice entered torpor during the dark phase. The degree of
      hypometabolism (5-22 ml h(-1)) and hypothermia (19.5-26.7 degrees C) was
      comparable in wildtype and UCP1-ablated mice, and both genotypes were able to
      regain normothermia. In contrast to wildtype mice, UCP1-ablated mice did not
      display multiple torpor bouts per day and their peak rewarming rates from torpor
      were reduced by 50% (UCP1(+/+): 0.24 +/- 0.08 degrees C min(-1); UCP1(-/-): 0.12
      +/- 0.04 degrees C min(-1)). UCP1-ablated mice therefore took significantly
      longer to rewarm from 25 to 32 degrees C (39 vs. 70 min) and required 60% more
      energy for this process. Our results demonstrate the energetic benefit of
      functional BAT for rapid arousal from torpor. They also suggest that torpor entry
      and maintenance may be dependent on endogenous rhythms.

PMID- 20680296
TI  - Differential changes of regional cerebral blood flow in two bat species during
      induced hypothermia measured by perfusion-weighted magnetic resonance imaging.
AB  - Cerebral blood flow (CBF) of a vespertilionid bat, Miniopterus fuliginosus (M.
      f.), and a pteropodid bat, Rousettus leschenaultii (R. l.) was measured non
      invasively during induced hypothermia (37-10 degrees C for M. f. and 37-24
      degrees C for R. l.) with perfusion-weighted magnetic resonance imaging. In both
      species, the average CBF was found to decrease with rectal temperature. The
      patterns of hypothermia-induced regional CBF changes, however, were different
      between the two species. In the pteropodid bat, the extent of CBF decrease at
      lower rectal temperature was similar in the cortex and thalamus, resulting in an
      unchanged thalamus/cortex CBF ratio. In contrast, the thalamus/cortex CBF ratio
      in the vespertilionid species increased progressively with decreasing rectal
      temperature (1.52 +/- 0.14 at 37 +/- 1 degrees C vs. 2.28 +/- 0.29 at 10 +/- 1
      degrees C). These results suggest that the manner in which the two bat species
      cope with low body temperature may be reflected by a differential CBF regulation
      between thalamus and cortex.

PMID- 20680297
TI  - Thermal acclimation, mitochondrial capacities and organ metabolic profiles in a
      reptile (Alligator mississippiensis).
AB  - Reptiles thermoregulate behaviourally, but change their preferred temperature and
      the optimal temperature for performance seasonally. We evaluated whether the
      digestive and locomotor systems of the alligator show parallel metabolic
      adjustments during thermal acclimation. To this end, we allowed juvenile
      alligators to grow under thermal conditions typical of winter and summer,
      providing them with seasonally appropriate basking opportunities. Although mean
      body temperatures of alligators in these groups differed by approximately 10
      degrees C, their growth and final anatomic status was equivalent. While hepatic
      mitochondria isolated from cold-acclimated alligators had higher oxidative
      capacities at 30 degrees C than those from warm-acclimated alligators, the
      capacities did not differ at 20 degrees C. Cold acclimation decreased maximal
      oxidative capacities of muscle mitochondria. For mitochondria from both organs
      and acclimation groups, palmitate increased oligomycin-inhibited respiration. GDP
      addition reduced palmitate-uncoupled rates more in liver mitochondria from warm-
      than cold-acclimated alligators. In muscle mitochondria, carboxyatractyloside
      significantly reduced palmitate-uncoupled rates. This effect was not changed by
      thermal acclimation. The aerobic capacity of liver, skeletal muscle and duodenum,
      as estimated by activities of cytochrome c oxidase (COX), increased with cold
      acclimation. At acclimation temperatures, the activities of COX and citrate
      synthase (CS) in these organs were equivalent. By measuring COX and CS in
      isolated mitochondria and tissue extracts, we estimated that cold acclimation did
      not change the mitochondrial content in liver, but increased that of muscle. The
      thermal compensation of growth rates and of the aerobic capacity of the locomotor
      and digestive systems suggests that alligators optimised metabolic processes for
      the seasonally altered, preferred body temperature. The precision of this
      compensatory response exceeds that typically shown by aquatic ectotherms whose
      body temperatures are at the mercy of their habitat.

PMID- 20680298
TI  - Posterior fossa ependymomas: new radiological classification with surgical
      correlation.
AB  - PURPOSE: The key determinant of long-term outcome in infratentorial ependymomas
      remains the extent of surgical resection. We describe a new radiological
      classification system which is validated against surgical findings and correlated
      with risk of post-operative residual tumour. METHODS: Twenty-five consecutive
      patients (12 females, mean age 4.9 years, range 0.5-17 years) with infratentorial
      ependymomas were studied. Lesions were classified on pre-operative MRI according
      to the pattern of extension, brainstem displacement and involvement of the obex,
      as lateral-type or midfloor-type tumours. Twenty-one operative records were
      reviewed with respect to the microanatomical tumour origin by a paediatric
      neurosurgeon, blinded to MRI findings. Follow-up imaging studies were evaluated
      for residual tumour. RESULTS: There were 15 cases of midfloor-type tumour
      (anterior displacement of brainstem, infiltration of obex) and 10 cases of
      lateral-type tumour (lateral displacement of brainstem, obex free of tumour).
      Extension into prepontine or cerebellopontine cisterns was more common in lateral
      type tumours. Agreement between the radiological classification and tumour
      origin, as defined by operative records, was seen in 18 out of 20 cases. Risk of
      residual tumour in lateral-type tumours was more than twice that of midfloor-type
      tumours (80% vs. 33%, p=0.04). Risk of tumour residual was also significantly
      higher when vessel encasement or prepontine extension was observed. CONCLUSIONS:
      Infratentorial ependymomas can be pre-operatively classified as lateral-type or
      midfloor-type tumours. This correlates well with operative findings. Lateral-type
      tumours have significantly increased risk of residual tumour compared to midfloor
      type tumours and this may influence intensity of imaging surveillance.

PMID- 20680299
TI  - Comment to the article entitled "Complexity analysis of the cerebrospinal fluid
      pulse waveform during infusion studies" CNS-10-0256.

PMID- 20680300
TI  - Complexity analysis of the cerebrospinal fluid pulse waveform during infusion
      studies.
AB  - PURPOSE: Nonlinear dynamics has enhanced the diagnostic abilities of some
      physiological signals. Recent studies have shown that the complexity of the
      intracranial pressure waveform decreases during periods of intracranial
      hypertension in paediatric patients with acute brain injury. We wanted to assess
      changes in the complexity of the cerebrospinal fluid (CSF) pressure signal over
      the large range covered during the study of CSF circulation with infusion
      studies. METHODS: We performed 37 infusion studies in patients with hydrocephalus
      of various types and origin (median age 71 years; interquartile range 60-77
      years). After 5 min of baseline measurement, infusion was started at a rate of
      1.5 ml/min until a plateau was reached. Once the infusion finished, CSF pressure
      was recorded until it returned to baseline. We analysed CSF pressure signals
      using the Lempel-Ziv (LZ) complexity measure. To characterise more accurately the
      behaviour of LZ complexity, the study was segmented into four periods: basal,
      early infusion, plateau and recovery. RESULTS: The LZ complexity of the CSF
      pressure decreased in the plateau of the infusion study compared to the basal
      complexity (p=0.0018). This indicates loss of complexity of the CSF pulse
      waveform with intracranial hypertension. We also noted that the level of
      complexity begins to increase when the infusion is interrupted and CSF pressure
      drops towards the initial values. CONCLUSIONS: The LZ complexity decreases when
      CSF pressure reaches the range of intracranial hypertension during infusion
      studies. This finding provides further evidence of a phenomenon of
      decomplexification in the pulsatile component of the pressure signal during
      intracranial hypertension.

PMID- 20680302
TI  - Bilateral adrenal haemorrhage following right hemicolectomy.

PMID- 20680301
TI  - Increased expression of L-amino acid transporters in balloon cells of tuberous
      sclerosis.
AB  - OBJECTS: Tuberous sclerosis complex (TSC) is a dysgenetic syndrome involved in
      multiple organs, and the pathognomonic cortical tuber act as an epileptic
      substrate. The amino acid transport system L (LAT) is a major nutrient transport
      system, and LAT1 is highly expressed in malignant tumors to support tumor cell
      growth. To study the life-long epilepsy from the cortical tuber, the expression
      of LAT1 in balloon cells and dysplastic neurons of the cortical tuber is
      investigated. MATERIALS AND METHODS: LAT1 expression was investigated by LAT1
      mRNA using reverse transcription-polymerase chain reaction and
      immunohistochemical staining with anti-human LAT1 antibody in nine patients with
      TSC and three control brains. CONCLUSION: LAT1 mRNA was detectable only in fresh
      frozen tissues of TSC, and it was upregulated in the cortical tuber lesion. While
      the LAT1 immunopositivity of control brains was limited in the capillary
      endothelial cells in the gray matter, increased LAT1 immunopositivity was noted
      in balloon cells of the cortical tubers in addition to the capillary endothelial
      cells as shown in control brains. Linear and strong immunopositivity along the
      cell membrane and cytoplasm of the balloon cells, and weakly granular
      immunopositivity in their cytoplasm were noted. Increased expression of LAT1 in
      the balloon cells is important for the active transport of large neutral amino
      acids into the balloon cells, and that the biologic process may play an important
      role in the active protein synthesis with metabolic maintenance of balloon cells
      in cortical tubers of patients with TSC.

PMID- 20680303
TI  - The comparison of the clinical manifestations and risk factors of colorectal
      cancer and adenomas: results from a colonoscopy-based study in southern Chinese.
AB  - BACKGROUND AND AIMS: Colorectal cancer (CRC) is one of the most common
      gastrointestinal tumors in the world. This study aimed to compare the clinical
      manifestations and risk factors of CRC and adenomas in native patients of
      Guangzhou. METHODS: Patients who underwent colonoscopy for the first time at
      Nanfang Hospital between July 2008 and July 2009 were recruited. Data on
      demographic information, main clinical manifestations, results of endoscopies and
      pathology, and possible risk factors of colorectal tumor were collected. Chi
      square test and logistic regression were used to compare the clinical
      characteristics and risk factors for CRC and adenomas. RESULTS: Hematochezia and
      body weight loss were more frequent in proximal and distal CRC groups,
      respectively (P <=  0.05). Older age [odds ratio (OR), 1.079; 95% confidence
      interval (CI), 1.065-1.093], smoking status (OR, 1.712; 95% CI, 1.158-2.531), BMI
      =18.5-24.9 and  >= 25.0 (OR, 2.384; 95% CI, 1.250-4.549; OR, 2.162; 95% CI, 1.044
      4.478, respectively) were significant risk factors for advanced adenoma, while
      female (OR, 0.638; 95% CI, 0.429-0.949) and using aspirin (OR, 0.188; 95% CI,
      0.042-0.845) were significant protective factors. Hyperlipemia (OR, 0.109; 95%
      CI, 0.013-0.886) was identified as a protective factor for proximal CRC. Smoking
      (OR, 1.717; 95% CI, 1.093-2.696), drinking (OR, 1.817; 95% CI, 1.145-2.883), DM
      history (OR, 2.204; 95% CI, 1.044-4.652) were identified as independent risk
      factors for distal CRC, and using aspirin (OR, 0.190; 95% CI, 0.043-0.840) was a
      protective factor. Drinking (OR, 3.288; 95% CI, 1.546-6.994; OR, 1.862; 95% CI,
      1.037-3.343, respectively) was an independent risk factor for both poorly to
      moderately differentiated CRC and well-differentiated CRC. Besides, DM (OR,
      3.761; 95% CI, 1.615-8.762) and hypertension (OR, 0.384; 95% CI, 0.178-0.828)
      were identified as independent risk factor and protective factor for well
      differentiated CRC, respectively. CONCLUSIONS: Hematochezia and body weight loss
      were representative manifestations for distal and proximal CRC, respectively. For
      southern Chinese the most important influential factors for colorectal tumor are
      age, smoking, drinking, nutritional state, DM, hypertension, and the use of
      aspirin.

PMID- 20680304
TI  - Stem cells in colon cancer. A new era in cancer theory begins.
AB  - INTRODUCTION: Despite the various therapeutic combinations and the emergence of
      new targeted therapies, there is still no curative treatment for all stages of
      colorectal cancer. Through the query for the best possible combination and
      solution, a new theory approaching colorectal cancer as a stem cell disease
      appeared, with a continuously growing body of evidence supporting this idea. The
      inability to directly recognize cancer stem cells has led researchers to an
      attempt of distinguishing those using indirect markers. DISCUSSION: This review
      focuses on colon cancer stem cell theory, the various findings supporting and
      contradicting this hypothesis, and the markers used up to now in characterizing
      stem cell populations in colorectal cancer. Despite the numerous unanswered
      questions on this new cancer hypothesis, it appears to have a justifiable role to
      play in colorectal cancer tumor biology, and furthermore, it may be the basis for
      the development of new therapeutic agents of the future. Therefore, every
      surgeon, oncologist, and physician who is implicated with this disease should be
      familiar with this novel colorectal cancer theory.

PMID- 20680306
TI  - Cardiological evaluation after cerebral ischaemia : Consensus statement of the
      Working Group Heart and Brain of the German Cardiac Society-Cardiovascular
      Research (DGK) and the German Stroke Society (DSG).
AB  - The cardiological evaluation of patients with cerebral ischaemia is of great
      clinical importance because diseases of the heart and aorta represent important
      sources of embolism, because ischaemic stroke is an index event that can lead to
      the diagnosis of cardiovascular diseases and because the mortality and morbidity
      of stroke patients are determined by concomitant cardiac diseases. Despite the
      importance of cardiological examinations for patients with ischaemic strokes, the
      topic is only addressed by few prospective clinical studies. Therefore, this
      interdisciplinary consensus document was developed to summarise the available
      information and to make expert recommendations for the evaluation of
      cardiovascular risk markers, electrocardiographic examinations, echocardiography
      and the indications for further investigations of a cardiac disease.

PMID- 20680308
TI  - Transverse fractures of the olecranon: a biomechanical comparison of three
      fixation techniques.
AB  - INTRODUCTION: The gold standard for treating transverse olecranon fractures is
      tension band fixation. A problem with this technique is migration of the K-wires
      leading to premature hardware removal. The aim of this study is to compare
      stability provided by two new techniques designed to eliminate the problem with
      backing out of K-wires, with that of the recommended tension band technique,
      performed with a biomechanical in vitro investigation. Our hypothesis was that
      the two new techniques would provide at least equal stability as the traditional
      tension band fixation. METHODS: Transverse olecranon osteotomies were created in
      human cadaveric elbows to simulate a type 21-B1.1 fracture. Three groups of 8
      specimens were instrumented with: (1) recommended AO tension band technique; (2)
      modified K-wires with eyelets and tension band; (3) staples across the fracture
      with tension band. Each elbow was tested in a 90 degrees  flexed position. The
      triceps tendon was sinusoidally loaded by applying two load steps at 500 and 700
      N for 4000 cycles each. Relative movements between the fragments were determined.
      RESULTS: At the end of the first and second load step the displacement of the
      osteotomy at the posterior ulnar side was significantly less for the staples
      across the fracture with tension band as compared to both other groups. There
      were no significant differences between groups 1 and 2. CONCLUSION: Since
      clinical results depend partly on stable fixation, it is concluded that using
      staples in the clinical situation might provide better results than the currently
      recommended tension band technique.

PMID- 20680307
TI  - TNFalpha protects cardiac mitochondria independently of its cell surface
      receptors.
AB  - Our novel proposal is that TNFalpha exerts a direct effect on mitochondrial
      respiratory function in the heart, independently of its cell surface receptors.
      TNFalpha-induced cardioprotection is known to involve reactive oxygen species
      (ROS) and sphingolipids. We therefore further propose that this direct
      mitochondrial effect is mediated via ROS and sphingolipids. The protective
      concentration of TNFalpha (0.5 ng/ml) was added to isolated heart mitochondria
      from black 6 * 129 mice (WT) and double TNF receptor knockout mice (TNFR1&2(-/
      )). Respiratory parameters and inner mitochondrial membrane potential were
      analyzed in the presence/absence of two antioxidants, N-acetyl-L: -cysteine or N
      tert-butyl-alpha-(2-sulfophenyl)nitrone or two antagonists of the sphingolipid
      pathway, N-oleoylethanolamine (NOE) or imipramine. In WT, TNFalpha reduced State
      3 respiration from 279.3 +/- 3 to 119.3 +/- 2 (nmol O2/mg protein/min), increased
      proton leak from 15.7 +/- 0.6% (control) to 36.6 +/- 4.4%, and decreased membrane
      potential by 20.5 +/- 3.1% compared to control groups. In TNFR1&2(-/-) mice,
      TNFalpha reduced State 3 respiration from 205.2 +/- 4 to 75.7 +/- 1 (p < 0.05 vs.
      respective control). In WT mice, both antioxidants added with TNFalpha restored
      State 3 respiration to 269.2 +/- 2 and 257.6 +/- 2, respectively. Imipramine and
      NOE also restored State 3 respiration to 248.4 +/- 2 and 249.0 +/- 2,
      respectively (p < 0.01 vs. TNFalpha alone). Similarly, both antioxidant and
      inhibitors of the sphingolipid pathway restored the proton leak to pre-TNF
      values. TNFalpha-treated mitochondria or isolated cardiac muscle fibers showed an
      increase in respiration after anoxia-reoxygenation, but this effect was lost in
      the presence of an antioxidant or NOE. Similar data were obtained in TNFR1&2(-/-)
      mice. TNFalpha exerts a protective effect on respiratory function in isolated
      mitochondria subjected to an anoxia-reoxygenation insult. This effect appears to
      be independent of its cell surface receptors, but is likely to be mediated by ROS
      and sphingolipids.

PMID- 20680309
TI  - Laparoscopic nerve-sparing surgery of deep infiltrating endometriosis:
      description of the technique and patients' outcome.
AB  - INTRODUCTION: The radical surgery of the deep infiltrating endometriosis of the
      rectovaginal septum and the uterosacral ligaments with or without bowel resection
      can cause a serious damage of the pelvic autonomic nerves with urinary retention
      and the need of self-catheterization. PATIENTS AND METHODS: We introduce a case
      series report of 16 patients with laparoscopic nerve-sparing surgery of deep
      infiltrating endometriosis. We describe the technique step by step and compare
      the patients' outcome with patients who had undergone a non-nerve-sparing
      surgical technique. In 12 patients, a double-sided and in four patients, a single
      sided identification of the inferior hypogastric nerve and plexus were performed.
      RESULTS: In all patients at least single-sided resection of the uterosacral
      ligaments were performed. Postoperatively dysmenorrhoea, pelvic pain, and
      dyspareunia disappeared in all patients. The average operating time was 82 min
      (range 45-185). Postoperatively, the overall time to resume voiding function was
      2 days. The residual urine volume was in all patients <50 ml at two ultrasound
      measurements. DISCUSSION: Identification of the inferior hypogastric nerve and
      plexus was feasible. In comparison with non-nerve-sparing surgical technique, no
      cases of bladder self-catheterization for a long or even life time was observed,
      confirming the importance of the nerve-sparing surgical procedure.

PMID- 20680310
TI  - Nucleotide variations in mitochondrial DNA and supra-physiological ROS levels in
      cytogenetically normal cases of premature ovarian insufficiency.
AB  - Premature ovarian insufficiency (POI) is defined as the cessation of ovarian
      function under the age of 40 years and is characterized by amenorrhea,
      hypoestrogenism, and elevated serum gonadotrophin concentration (FSH). It is a
      heterogeneous disorder with a multicausal pathogenesis; however, majority of
      cases are idiopathic. In idiopathic POI, involvement of unknown mechanisms may
      increase rate of oocyte apoptosis. Studies have shown that elevated reactive
      oxygen species (ROS) levels affect the quality of gametes. Mitochondrial
      mutations in different complexes of electron transport chain have been reported
      to disrupt the electron flow which lead to formation of more superoxide ions or
      increased levels of ROS. This study was aimed to screen the mitochondrial genome
      for variations in idiopathic POI (n = 25) and occult ovarian insufficiency (OI)
      (n = 5) patients. 30 patients diagnosed with POI and occult OI were enrolled in
      this study. Blood samples were collected from the patients and controls. DNA was
      extracted using phenol chloroform method. A total of 102 nucleotide variations
      were observed in patients as compared with 58 nucleotide variations in controls.
      24% variations were found to be non-synonymous and 76% were synonymous. It was
      found that 48% variations were in complex I, 8% in complex III, 24% in complex
      IV, and 20% in complex V of electron transport chain. We found most of the non
      synonymous mitochondrial variations in complex I (48%) of the respiratory chain
      which is the largest enzyme complex and is associated with oxidative stress. Some
      non-synonymous pathogenic alterations (p.M31T, p.W239C, p.L128Q) and non
      pathogenic alterations (ATPase6:p.T53I, ATPase6:p.L190F, ATPase6:p.L199L) were
      found to be significantly higher in cases as compared with controls. The
      preliminary data suggest that the mitochondrial mutations and subsequent decline
      in ATP levels may accelerate follicular atresia and lead to POI. The results of
      this preliminary study highlight the need to extend this study by analyzing large
      number of samples in different ethnic populations and analyze for ROS levels and
      mitochondrial mutations in oocytes as they are of different embryonic origin and
      develop in a different microenvironment.

PMID- 20680312
TI  - Continuous versus interrupted episiotomy repair with monofilament or
      multifilament absorbed suture materials: a randomised controlled trial.
AB  - PURPOSE: To compare different repair techniques and different suture materials
      for episiotomy. METHODS: 160 women having vertex delivery with right-mediolateral
      episiotomy were randomly allocated to four groups. In the groups where continuos
      technique was performed, vaginal mucosa, perineal muscles and the skin were
      sutured continuously. In the groups of interrupted technique, vaginal mucosa was
      sutured with continuous sutures, then muscle layers and skin were closed by
      interrupted sutures. Two different types of synthetic absorbed suture material
      were used: monofilament type is in form of polyglycolide-co-caprolactone and
      multifilament one is polyglactin 910-Rapide. Perineal pain during different
      activities on the first and tenth day postpartum and also during sexual
      intercourse 6 weeks after the delivery was questioned by visual analogous scale
      (VAS). Furthermore, repair time, amount of suture and episiotomy complications
      were investigated in each groups. RESULTS: On the first day after delivery, the
      perineal pain scores, the repair time, the amount of suture were statistically
      less in the continuous technique groups. The differences between the pain at
      tenth day and during sexual intercourse 6 weeks after the delivery were
      statistically same. CONCLUSIONS: The continuous suturing techniques for
      episiotomy closure, compared to interrupted methods, are associated with less
      short-term pain, are quicker and also need less suture material.

PMID- 20680311
TI  - Perioperative complications in conventional and microsurgical abdominal
      myomectomy.
AB  - PURPOSE: It has become evident that laparoscopic myomectomy is limited by size,
      number and location of fibroids. Myomectomy performed by laparotomy can be
      technically challenging and the surgical benefits have to be weighed against
      associated risks and impairing fertile potential, especially in multiple and
      large fibroids that may be positioned close to the cavity. Our aim was to
      evaluate the effect of microsurgical myomectomy technique on perioperative
      morbidity in premenopausal women. METHODS: This retrospective study included 228
      patients with symptomatic uterine fibroids and/or infertility undergoing
      myomectomy by laparotomy. As much as 156 patients were treated by standardized
      microsurgical technique and 72 patients by conventional myomectomy. The following
      data were recorded and analysed: postoperative haemoglobin, haemoglobin decrease,
      rate of blood transfusion, and number, size and location of myomas. RESULTS: In
      228 patients, seven complications occurred (abdominal wall haematoma, bowel and
      colon injury, transient ileus). The transfusion rate was 1.3%. Microsurgical
      technique was associated with a smaller haemoglobin decrease compared to
      conventional myomectomy (1.77 vs. 2.38 g/dl; P = 0.007). Microsurgical technique
      correlated inversely with haemoglobin decrease (P < 0.001). Haemoglobin decrease
      correlated positively with myoma number (P < 0.001), size of myoma (P < 0.001)
      and the opening of the cavum uteri (P = 0.014). CONCLUSIONS: In this large series
      of abdominal myomectomies, procedure-related morbidity, mainly perioperative
      blood loss, was amongst the lowest reported when microsurgical techniques were
      used. In patients with multiple, large or deep intramural fibroids who desire
      future pregnancies, the use of microsurgical techniques may decrease
      intraoperative blood loss and perioperative morbidity.

PMID- 20680313
TI  - Pregnancy outcome in systemic lupus erythematosus: Asia's largest single centre
      study.
AB  - AIM: To evaluate pregnancy outcome in women with systemic lupus erythematosus
      (SLE). METHODS: A total of 71 pregnancies in 35 women with SLE were evaluated for
      maternal and perinatal outcomes in a tertiary centre of Northern India. Thirty
      five pregnancies were evaluated prospectively while details of previous 36
      pregnancies in the same women were studied retrospectively. RESULTS: The Mean age
      of pregnant women with SLE was 26.89 +/- 2.7 years and 14.57% were nulliparous.
      The presenting event was arthritis in 60% of the patients; others presented with
      febrile illness, renal manifestation and cutaneous manifestation. One woman was
      lupus anticoagulant positive. All women conceived while on disease quiescence
      period and were continued on the same pre-pregnancy dose of pharmacological
      agents. Hypertensive disorders of pregnancy were seen in 28.5% while chronic
      hypertension was seen in 5.6%. The incidence of abortion, preterm deliveries and
      perinatal loss was 33.8, 29.57 and 12.67%, respectively. Vaginal delivery rate
      was 47.88 and 18.3% underwent caesarean section. There was no case of neonatal
      lupus and none had disease flare-up in the postpartum period. CONCLUSION: A
      better pregnancy outcome can be expected if clinical remission is achieved and
      disease activity is adequately controlled prior to pregnancy.

PMID- 20680315
TI  - Umbilical hemangioma: a case report.
AB  - INTRODUCTION: Umbilical cord tumors are extremely rare with hemangiomas and
      teratomas accounting for the most common tumors. CASE REPORT: A 26-year-old woman
      had an anomaly scan at 22 weeks. There was an echogenic area in the umbilical
      cord, the mass, which appeared enlarged and oedematous findings represented an
      umbilical cord hemangioma, but no fetal abnormalities (Fig. 1). The second
      ultrasound examination for follow-up showed that the fetus was dead. The
      macerating fetus (46XY) weighing 650 g was autopsied, and the report confirmed
      umbilical cord hemangioma and no significant congenital abnormalities (Figs. 2,
      3). DISCUSSION: A high perinatal mortality and morbidity rate has been reported
      with hemangiomas of umbilical cord. Impaired umbilical circulation is considered
      as the predisposing factor for fetal demise. It is associated with premature
      delivery, cardiac failure, severe fetal hemorrhage, IUGR and intrauterine death.
      The differential diagnosis of umbilical cord hemangioma should include hematomas,
      varices, aneurysms, thrombosis and tumors. Close antenatal follow-up is
      mandatory, with serial USS examinations, which should involve AFI, tumor size and
      Doppler studies. The examination should be at 4 weeks intervals up to 32-34 weeks
      and every 1-2 weeks thereafter depending on the findings. CONCLUSION: The
      prenatal diagnosis of umbilical cord hemangioma should be suspected when an
      echogenic mass is visualized within the umbilical cord.

PMID- 20680314
TI  - Factors associated with recurrence of cervical intraepithelial neoplasia after
      conization in HIV-infected and noninfected women.
AB  - PURPOSE: To identify risk factors associated with recurrence of cervical
      intraepithelial neoplasia (CIN) following loop electrosurgical excision
      procedures in women with and without human immunodeficiency virus (HIV). METHODS:
      A total of 33 patients with recurrent CIN and 105 without recurrence were
      contrasted using a nested case-control design. The patients were enrolled between
      1999 and 2004. Recurrence diagnosis was established after conization, and tissues
      were fixed in formalin and embedded in paraffin. Polymerase chain reaction was
      used to detect the human papillomavirus genome (HPV DNA) types 6, 11, 16, 18, 31,
      33, and 35. Statistical analysis was performed using chi2 test with Yates
      correction and the Fisher's exact test for comparison of categorical variables.
      Multivariate analysis was carried out using logistic regression models. RESULTS:
      Human immunodeficiency virus infection (p = 0.001), glandular involvement (p =
      0.000), and compromised margins (p = 0.02) were significantly associated with CIN
      recurrence. HPV DNA was positive in 57.6% of patients with CIN recurrence. High
      risk HPV subtypes were detected in most cases but were not associated with
      recurrence (p = 0.27). In multivariate analysis, HIV infection and glandular
      involvement were independently associated with CIN recurrence. CONCLUSIONS: Human
      immunodeficiency virus infection and glandular involvement are associated with
      CIN recurrence.

PMID- 20680316
TI  - The association with age, human tissue kallikreins 6 and 10 and hemostatic
      markers for survival outcome from epithelial ovarian cancer.
AB  - PURPOSE: To assess known cancer biomarkers CA-125, human tissue kallikreins KLK6
      and KLK10, hemostatic markers and age with 5-year survival outcome from
      epithelial ovarian cancer. METHODS: Forty-one benign cyst cohorts and 83 patients
      diagnosed with ovarian cancer were recruited. The following assays were
      performed: fibrinogen, vWF antigen, D: -dimer, ATIII activity, tPA, PAI-1, uPAR,
      KLK6, KLK10 and CA-125. Follow-up visits of cancer patients of more than 60
      months were noted. Data between those who survived past 60 months and mortality
      from cancer were analyzed. RESULTS: Only 24 patients lived past 60 months, and 31
      died (advanced stage n = 27). Those living past 60 months were significantly
      older and associated with similar pre-operative levels seen in benign cyst
      cohorts especially for KLK6, fibrinogen, vWF, AT levels despite upregulation of
      D: -dimer, CA-125 and KLK10. Ovarian cancer cohorts living past 60 months were
      younger than those who died within 12 months (n = 12). Mortality within 12 months
      was associated with older age, upregulation of KLK6, fibrinogen, D: -dimer, vWF,
      tPA antigen and reduced ATIII levels. Similarly, mortality within 36 months of
      disease showed older age with upregulation of CA-125, KLK6 D: -dimer vWF antigen
      and tPA antigen levels. Late stage cancer (III/IV) showed upregulated CA-125,
      KLK6, KLK10, D: -dimer and reduced AT compared to early stage cancer (I/II). The
      5-year survival rate for early cancer was 80%, advanced 22.9% and overall 5-year
      survival rate was 43.6%. CONCLUSION: Older age together with the novel biomarkers
      studied and their association with adverse outcome from epithelial ovarian cancer
      was seen especially within 12 and 36 months of disease. Those who lived past 60
      months of disease showed similar pre-operative levels seen in benign cyst cohorts
      despite elevated D: -dimer, CA125 and KLK 10. An enlarged study is needed to
      confirm these findings.

PMID- 20680317
TI  - Regulation of DNA replication by chromatin structures: accessibility and
      recruitment.
AB  - The initiation of DNA replication and the elongation of DNA strands take place in
      chromatin, a huge compound DNA-protein complex. Although the factors involved in
      the process of DNA replication have been largely elucidated, the underlying
      mechanisms that determine their behavior in the context of chromatin have only
      recently begun to be understood. It has been known that transcription is tightly
      regulated by the state of chromatin compaction, which governs the accessibility
      of DNA to trans-acting factors. This process is influenced by several
      determinants of chromatin structure, including intrinsic nucleosome positioning,
      the nucleosome remodeling complex, histone post-translational modifiers, and
      histone- and DNA-binding proteins. Growing evidence indicates that this concept
      is also applicable to the regulation of DNA replication. In addition, recent
      studies have demonstrated a distinctive mode of regulation. Some non-histone
      chromatin-binding proteins have been shown to interact physically with
      replication factors, thereby facilitating their recruitment at specific
      chromosomal loci. This type of regulation may allow control of local replication
      activity without affecting other chromosomal processes.

PMID- 20680319
TI  - Dental age assessment (DAA): reference data for British children at the 10-year
      old threshold.
AB  - The purpose of this work was to develop a reference dataset for dental age
      assessment at the 10-year-old threshold. Dental panoramic radiographs of children
      aged between 9 and 11 years were reused to determine the age of attainment of
      tooth development stages relevant to the 10-year threshold. These data were used
      to test the accuracy of the dental age assessment (DAA) on a separate study
      sample of known chronological age. The study sample comprised 100 radiographs (50
      female, 50 male) of known chronological age that did not form part of the
      reference dataset. For each subject in the study sample, the mathematical
      procedure used in meta-analysis was applied to all teeth that were still
      developing. The weighted average of all the developing teeth in a given child was
      assigned as the dental age for that individual. This was compared to the gold
      standard of chronological age. Three thousand six hundred sixty-two radiographs
      comprised the reference sample. The mean difference between the chronological age
      and dental age estimated for the sample of female subjects was 0.12 years (1.44
      months) and for the males was 0.33 years (3.96 months). A method comparison
      technique was used to evaluate the difference between the chronological age and
      estimated dental age for each study subject. This showed a good agreement for
      both females and males. DAA using meta-analysis provides a simple method of
      estimating the age of subjects of unknown birth date at the 10-year threshold.
      This is, presently, the most accurate method of age assessment for individuals of
      unknown date of birth.

PMID- 20680318
TI  - Laser capture microdissection in forensic research: a review.
AB  - In forensic sciences, short tandem repeat (STR) analysis has become the prime
      tool for DNA-based identification of the donor(s) of biological stains and/or
      traces. Many traces, however, contain cells and, hence, DNA, from more than a
      single individual, giving rise to mixed genotypes and the subsequent difficulties
      in interpreting the results. An even more challenging situation occurs when cells
      of a victim are much more abundant than the cells of the perpetrator. Therefore,
      the forensic community seeks to improve cell-separation methods in order to
      generate single-donor cell populations from a mixed trace in order to facilitate
      DNA typing and identification. Laser capture microdissection (LCM) offers a
      valuable tool for precise separation of specific cells. This review summarises
      all possible forensic applications of LCM, gives an overview of the staining and
      detection options, including automated detection and retrieval of cells of
      interest, and reviews the DNA extraction protocols compatible with LCM of cells
      from forensic samples.

PMID- 20680323
TI  - Patching improves perfusion of the sagged brain in intracranial hypotension.

PMID- 20680322
TI  - Changes in interhemispheric inhibition following successful epilepsy surgery: a
      TMS study.
AB  - Epileptic foci can influence cortical excitability, brain perfusion and
      metabolism not only directly in the focus or perifocally, but also in remote
      areas. Effects of successful epilepsy surgery on cortical networks and changes in
      excitability have rarely been addressed. We report a study on changes in
      interhemispheric inhibition following successful surgical removal of an epileptic
      focus. Eighteen patients (11 females, 7 males, mean age 34.2 years) were enrolled
      in this transcranial magnetic stimulation (TMS) study. All patients were seizure
      free after surgery and had identical antiepileptic medication pre- and
      postsurgically. Investigations were performed before and at least 3 months after
      surgery. Motor thresholds (MT) and motor evoked potentials (MEPs) of
      interhemispheric paired pulse paradigms were investigated on both hemispheres.
      Resection of the epileptic focus resulted in a significant change in
      interhemispheric inhibition (IHI). The ability of the non-focal hemisphere to
      inhibit the motor cortex (M1) of the focal hemisphere significantly increased
      (p=0.02) and normalized to the level of the other hemisphere. In summary, this
      TMS study suggests that an epileptic focus can modulate interhemispheric
      inhibitory interactions between the motor cortices. A decreased susceptibility of
      M1 of the focal hemisphere or alterations in the non-focal hemispheric inhibitory
      output may be underlying mechanisms. These findings may contribute to a better
      understanding of widespread functional impairments in focal epilepsy.

PMID- 20680324
TI  - Size of third and fourth ventricle in obstructive and communicating acute
      hydrocephalus after aneurysmal subarachnoid hemorrhage.
AB  - In patients with acute hydrocephalus after aneurysmal subarachnoid haemorrhage
      (SAH), lumbar drainage is possible if the obstruction is in the subarachnoid
      space (communicating hydrocephalus). In case of intraventricular obstruction
      (obstructive hydrocephalus), ventricular drainage is the only option. A small
      fourth ventricle is often considered a sign of obstructive hydrocephalus. We
      investigated whether the absolute or relative size of the fourth ventricle can
      indeed distinguish between these two types of hydrocephalus. On CT-scans of 76
      consecutive patients with acute headache but normal CT and CSF, we measured the
      cross-sectional surface of the third and fourth ventricle to obtain normal
      planimetric values. Subsequently we performed the same measurements on 117
      consecutive SAH patients with acute hydrocephalus. These patients were divided
      according to the distribution of blood on CT-scan into three groups: mainly
      intraventricular blood (n=15), mainly subarachnoid blood (n=54) and both
      intraventricular and subarachnoid blood (n=48). The size of the fourth ventricle
      exceeded the upper limit of normal in 2 of the 6 (33%) patients with
      intraventricular blood but without haematocephalus, and in 15 of the 54 (28%)
      patients with mainly subarachnoid blood. The mean ratio between the third and
      fourth ventricle was 1.45 (SD 0.66) in patients with intraventricular blood and
      1.42 (SD 0.91) in those with mainly subarachnoid blood. Neither fourth
      ventricular size nor the ratio between the third and fourth ventricles
      discriminates between the two groups. A small fourth ventricle does not
      necessarily accompany obstructive hydrocephalus and is therefore not a
      contraindication for lumbar drainage.

PMID- 20680325
TI  - Cortical excitability in very mild Alzheimer's disease: a long-term follow-up
      study.
AB  - Measurement of motor cortex excitability using paired-pulse transcranial magnetic
      stimulation (pTMS) has been proposed for the early diagnosis of Alzheimer's
      disease (AD) and could also be useful for monitoring treatment response and
      disease progression. However, studies conducted at the pre-dementia stage of AD
      are scarce, very few long-term data are available, and correlations between
      cortical excitability and cognitive performance have not been addressed. Eleven
      patients with mild cognitive impairment (MCI) that converted to AD-related
      dementia and 12 elderly control subjects were selected for this study. Cognitive
      assessments and pTMS were conducted at baseline in the two groups and also after
      4 and 21 months of treatment with donepezil in the AD group. Non-parametric
      statistics were used to compare cortical excitability between the two study
      groups at baseline and to analyse disease course in the AD group. Correlation
      analysis was performed to investigate associations between cortical excitability
      and cognitive performance. Short-latency intracortical inhibition (SICI) and
      intracortical facilitation were reduced in AD patients. However, there was high
      inter-individual variability, and statistical significance was only attained at a
      2-ms interstimulus interval (ISI). A trend towards recovery of 2-ms SICI was
      observed after treatment with donepezil. Baseline cortical excitability at 300 ms
      was associated with better cognitive performance in AD patients. Although the
      present results do not support a role for pTMS in the early diagnosis of late
      onset AD, a potential role in prediction of treatment response and understanding
      of disease mechanisms emerged.

PMID- 20680326
TI  - Duration of wet work in hairdressers.
AB  - AIM OF THE STUDY: Occupational contact dermatitis caused by wet work is
      particularly common in hairdressers. Data on the duration of wet work (DWW) in
      the hairdresser's trade are not well known until now. A questionnaire or self
      reported/estimated skin exposure are not suitable to get accurate information
      about DWW. According to the guidance of the German Federal Ministry for Labour
      and Social Affairs, employees with DWW > 2 h per day should get a possibility for
      targeted occupational-medical health examinations. Targeted occupational-medical
      health examinations are prescribed for employees with daily duration of wet work
      longer than 4 h. The aim of the study was to quantify the average daily
      exposition to wet work in hairdressers. MATERIALS AND METHODS: In our study, we
      used the direct observation as a standard method to analyse the work steps and to
      measure DWW in hairdressers. We developed the instrument for the analyses of
      activities in hairdresser salons and measurement of DWW in hairdressers during
      their 8-h shift. At the beginning of the study, 60 observers were intensively
      instructed and trained in the procedure of analysis. RESULTS: The mean of
      duration of wet work (DWW) in 106 8-h shifts analysed was 8,234 s (approx. 2 h 17
      min). The minimum of DWW was 278 s and the maximum 21,135 s (approx. 6 h); the
      standard deviation was 3,826 s. In 37% of the analysed 8-h shifts, DWW was
      shorter than 2 h, in 58% between 2 and 4 h and in 5% longer than 4 h. Eighteen
      per cent of the DWW was caused by wearing water-resistant protective gloves. We
      found positive correlations between "DWW" and "DWW > 2 h", with the predictors
      "number of customers total", "number of long-haired people" and "number of female
      customers". CONCLUSION: According to the guidance of the German Federal Ministry
      for Labour and Social Affairs, hairdressers should get a possibility for targeted
      occupational-medical health examinations.

PMID- 20680327
TI  - Reply to Nolte and Noakes' "comments on Baker et al.'s change in body mass
      accurately and reliably predicts change in body water after endurance exercise".

PMID- 20680328
TI  - Effects of exercise training on vasodilatory protein expression and activity in
      rats.
AB  - Increased endothelium-dependent vasodilatation is associated with endurance
      exercise training. The purpose of this study was to test the hypothesis that
      increased endothelial nitric oxide synthase (eNOS) protein function, but not
      increased vascular smooth muscle sensitivity to NO, underlies augmented
      endothelium-dependent dilatation with training. To test these hypotheses, rats
      ran on a treadmill at 30 m/min (10% grade) for 60 min/day, 5 days/week, over 8-12
      weeks (Trn). Training efficacy was demonstrated by greater (P < 0.05) hindlimb
      muscle citrate synthase activity and left ventricular mass-body mass ratio in Trn
      compared with sedentary control rats (Sed). Expression of eNOS protein in the
      aorta was increased with training (Sed, 1.00 +/- 0.18 normalized units; Trn, 1.55
      +/- 0.23; P < 0.05). Aortic NOS activity was, however, unchanged by training
      (Sed, 1,505 +/- 288 fmol/h/mg protein; Trn, 1,650 +/- 247; n.s.). Expression of
      heat shock protein 90 and protein kinase B/Akt was not different between groups,
      nor was their association with eNOS. In follow-up series of rats, phosphorylated
      eNOS content (Serine 1177) was similar for Sed and Trn in both the aorta and
      gastrocnemius feed artery. Aortic NOS activity with eNOS phosphorylation status
      preserved was also similar between groups. Finally, cGMP concentration with a NO
      donor did not differ between groups (Sed, 73.0 +/- 20.2 pmol/mg protein; Trn,
      62.5 +/- 12.9; n.s.). These findings indicate that training-induced increases in
      eNOS protein expression are not coupled to augmented function, illustrating the
      complexity of eNOS regulation. Further, they show that vascular sensitivity to NO
      is not altered by exercise training.

PMID- 20680329
TI  - The effect of sealing with a fixed combination of collagen matrix-bound
      coagulation factors on the healing of colonic anastomoses in experimental high
      risk mice models.
AB  - PURPOSE: Experimental and clinical studies on the sealing of colorectal
      anastomoses in order to reduce the rate of leakage have previously been performed
      with divergent results. However, comparatively few studies have been performed on
      anastomotic healing using a fibrin glue-coated patch. The aim of this
      experimental basic scientific study in mice was to investigate the effect of
      fibrin glue-coated collagen patches on the healing process of colonic anastomoses
      in situations of adverse healing process (technical deficiency and peritonitis).
      METHODS: Colonic anastomoses were carried out in 206 mice and randomized into six
      groups (I: complete anastomoses, II: sealed complete anastomoses, III: incomplete
      anastomoses, IV: sealed incomplete anastomoses, V: complete anastomoses in the
      presence of bacterial peritonitis, VI: sealed complete anastomoses in the
      presence of bacterial peritonitis). Tissues from the anastomoses were removed and
      used for functional, histochemical, molecular, and biochemical investigations.
      RESULTS: The evaluation of postoperative course data revealed the beneficial
      effect of additional sealing with a fixed combination of collagen matrix-bound
      coagulation factors I and IIa (Tachosil((r)), Nycomed Austria, Linz) in high-risk
      experimental anastomotic healing. Sealing incomplete anastomoses resulted in
      significantly lower lethality and leakage rates, as well as significantly higher
      bursting pressure values and histopathologic scores. Collagen 1 and 3 expressions
      and hydroxyproline concentrations are greatly increased with additional sealing
      in all high-risk anastomoses. CONCLUSIONS: In our current model, we demonstrate
      that additionally sealing high-risk experimental colonic anastomoses provides a
      positive effect on the healing process. The effect on the molecular level in
      particular seems to be essential and requires further experimental studies to
      evaluate the mechanism.

PMID- 20680330
TI  - Functional evolution of Ets in echinoderms with focus on the evolution of
      echinoderm larval skeletons.
AB  - Convergent evolution of echinoderm pluteus larva was examined from the standpoint
      of functional evolution of a transcription factor Ets1/2. In sea urchins, Ets1/2
      plays a central role in the differentiation of larval skeletogenic mesenchyme
      cells. In addition, Ets1/2 is suggested to be involved in adult skeletogenesis.
      Conversely, in starfish, although no skeletogenic cells differentiate during
      larval development, Ets1/2 is also expressed in the larval mesoderm. Here, we
      confirmed that the starfish Ets1/2 is indispensable for the differentiation of
      the larval mesoderm. This result led us to assume that, in the common ancestors
      of echinoderms, Ets1/2 activates the transcription of distinct gene sets, one for
      the differentiation of the larval mesoderm and the other for the development of
      the adult skeleton. Thus, the acquisition of the larval skeleton involved target
      switching of Ets1/2. Specifically, in the sea urchin lineage, Ets1/2 activated a
      downstream target gene set for skeletogenesis during larval development in
      addition to a mesoderm target set. We examined whether this heterochronic
      activation of the skeletogenic target set was achieved by the molecular evolution
      of the Ets1/2 transcription factor itself. We tested whether starfish Ets1/2
      induced skeletogenesis when injected into sea urchin eggs. We found that, in
      addition to ectopic induction of mesenchyme cells, starfish Ets1/2 can activate
      some parts of the skeletogenic pathway in these mesenchyme cells. Thus, we
      suggest that the nature of the transcription factor Ets1/2 did not change, but
      rather that some unidentified co-factor(s) for Ets1/2 may distinguish between
      targets for the larval mesoderm and for skeletogenesis. Identification of the co
      factor(s) will be key to understanding the molecular evolution underlying the
      evolution of the pluteus larvae.

PMID- 20680331
TI  - The birth of endocrine pathology: How Erdheim misunderstood parathyroids.

PMID- 20680332
TI  - Effectiveness of mefloquine against Clonorchis sinensis in rats and Paragonimus
      westermani in dogs.
AB  - The aim of the study is to explore the effect of mefloquine against Clonorchis
      sinensis and Paragonimus westermani. For anti-C. sinensis study, a total of 71
      rats were divided into four batches for oral infection of each rat with 50 C.
      sinensis metacercariae. Five to 7 weeks post-infection, groups of rats were
      treated orally with mefloquine at single doses or multiple daily doses while
      infected, but untreated rats served as control. All treated rats were euthanized
      2 weeks post-treatment for assessment of efficacy. For anti-P. westermani study,
      two batches of eight and ten dogs were each infected intraperitoneally with 100
      P. westermani metacercariae. Eighty-five to 96 days post-infection, groups of two
      or three dogs were treated orally with mefloquine and groups of two dogs were
      treated with praziquantel at a single dose or multiple doses. In each batch of
      test, three untreated but infected dogs served as control. All treated dogs were
      euthanized 26-30 days post-treatment for evaluation of efficacy. In rats infected
      with C. sinensis and treated orally with mefloquine at a single dose of 75 and
      150 mg/kg, no effect against C. sinensis was observed. When the dose of
      mefloquine was increased to 250 mg/kg, one third (five out of 15) rats died 3-5
      days post-treatment. Although the mean worm burden was lower than that of the
      control, the difference between the treated and control groups was not
      statistically significant (P>0.05) with worm burden reduction of 22.4%. Whereas,
      the group of infected rats received mefloquine at a daily dose of 100 mg/kg for 3
      days, one out of five rats died after the last administration. The mean worm
      burden was significantly lower than that of the control with worm burden
      reduction of 67.6% (P<0.01). In the first test of mefloquine against P.
      westermani, three infected dogs received two oral doses of the drug, 50 mg/kg,
      given at a 4-h interval, the mean worm burden were similar to that of the
      control. While other two dogs were treated with praziquantel at the same dose
      schedule, the worm burden reduction of 78% was observed. In the second test,
      three and two dogs were treated with mefloquine 50 mg/kg daily for 5 days or 100
      mg/kg daily for 2 days; the mean worm burdens of the two groups were lower than
      that of the control with worm burden reduction of 65.6% and 51.9%, respectively.
      However, only the difference of mean worm burdens between mefloquine 50 mg/kg
      given daily for 5 days and the control was statistically significant (P<0.05).
      Other two dogs treated with praziquantel at a single dose of 100 mg/kg were
      cured. The results indicate that under the appropriate dose schedule mefloquine
      exhibits less effect against C. sinensis in rats and P. westermani in dogs.

PMID- 20680333
TI  - In vitro antimalarial activity of traditionally used Western Ghats plants from
      India and their interactions with chloroquine against chloroquine-resistant
      Plasmodium falciparum.
AB  - Malaria is a major global public health problem, and the alarming spread of drug
      resistance and limited number of effective drugs now available underline how
      important it is to discover new antimalarial compounds. An ethnopharmacological
      investigation was undertaken on Western Ghats plants traditionally used to treat
      malaria in India; 50 plants were very carefully selected from a total of 372
      plants, and 200 extracts were prepared and tested for in vitro antiplasmodial
      activity alone and in combination with chloroquine (CQ) against CQ-resistant
      Plasmodium falciparum (strain MRC-Pf-43). In in vitro antiplasmodial activity,
      when plant extract alone is used, 29 extracts (or 14.5%) showed significant high
      in vitro antiplasmodial activity with IC(50) values ranging from 3.96 to 4.85
      MUg/ml, 53 extracts (or 26.5%) showed significant good in vitro antiplasmodial
      activity with IC(50) values ranging from 5.02 to 9.87 MUg/ml, and 28 extracts (or
      14%) showed significant moderate in vitro antiplasmodial activity with IC(50)
      values ranging from 10.87 to 14 MUg/ml, respectively. In combination with CQ, 103
      extracts (or 51.5%) showed significant synergistic in vitro antiplasmodial
      activities with synergistic factor values ranging from 1.03 to 1.92, and these
      activities were up to a fold higher with CQ, suggesting synergistic interactions
      of the two drugs. Our investigation has confirmed that above 62.1% of the plant
      extracts showed moderate to high in vitro antiplasmodial activity when used
      alone, and in combination with CQ, 55.7% of the extracts showed borderline to
      good synergistic activity.

PMID- 20680334
TI  - Survival of first stage larvae (L1) of Angiostrongylus vasorum under various
      conditions of temperature and humidity.
AB  - This experiment has been conducted to evaluate the viability of Angiostrongylus
      vasorum L1 under different conditions of temperature and humidity. In order to
      assess the viability, fox faecal pellets containing first stage larvae (L1) were
      exposed to relative humidity (RH) 95% and 75%, and to different temperatures (5
      degrees C, 18 degrees C) and at fluctuating conditions ranging from -5 degrees C
      to +5 degrees C. Moreover, larval viability under outdoor conditions in April was
      also observed. Survival of the larvae was strongly influenced by temperature;
      however, humidity did not show any significant influence on viability. In
      controlled condition, 100% of the larvae were found motile and active; whereas,
      around 14% and 19% of the larvae kept at 5 degrees C remained viable at RH 95%
      and RH 75%, respectively after 78 h. All of the larvae kept at 18 degrees C died
      after 66 h. In outdoor condition, larval survivability reduced to 18% after 66 h,
      and in fluctuation temperature viable larvae were observed in both control and
      experimental conditions (15%) after 78 h.

PMID- 20680335
TI  - Association of clomipramine and allopurinol for the treatment of the experimental
      infection with Trypanosoma cruzi.
AB  - We have previously shown that clomipramine and allopurinol used separately are
      effective in preventing chronic chagasic cardiomyopathy. The aim of the present
      study was to evaluate the effect of the association of clomipramine (Clo--5
      mg/kg/day/90 days) and allopurinol (Allo--5, 10, or 15 mg/kg/day/90 days) for the
      treatment of experimental Chagas disease in the acute stage. Treatment
      effectiveness was evaluated through parasitemia, survival, electrocardiography,
      serology, and cardiac histopathology. Groups treated showed no
      electrocardiographic abnormalities, in contrast to those untreated which
      presented 25% of mice with conduction alterations. The myocardium of treated mice
      (Clo, Allo10+Clo, and Allo15+Clo) presented no structural alterations. Cardiac b
      receptor affinity was preserved in mice treated with Clo or Clo+Allo at the
      different doses; receptor density of the Clo and Allo15+Clo groups did not differ
      from the non-infected group. Anti-cruzipain antibody levels were similar in
      treated and untreated groups. Survival was significantly increased in the treated
      groups (p < 0.05), with Clo and all the Clo+Allo groups presenting the highest
      rates. These results show that the association of clomipramine + allopurinol is
      effective for Chagas disease treatment and has the same effect as clomipramine
      alone.

PMID- 20680336
TI  - Chloromyxum aegypticus n. sp. (Myxozoa: Chloromyxidae) infecting the testicular
      tissue of the Egyptian toad, Bufo regularis (Amphibia: Bufonidae), and its
      pathogenicity.
AB  - A new myxosporean, Chloromyxum aegypticus n. sp., is described from the testes of
      the Egyptian toad Bufo regularis, captured from El Mansoura locality. C.
      aegypticus is identified on the basis of cytology, electron microscopy and
      histopathology. It is distinguished from all previously reported Chloromyxum spp.
      by its shape, dimensions of the mature spore (9.1 +/- 0.1 (9.0-9.2) MUm in length
      * 7.9 +/- 0.1 (7.8-8.0) MUm in width), polar capsules, external ridge,
      sporoplasm nuclei, undulating suture, locality and host. Accumulation of several
      hundreds of plasmodia (0.8 +/- 0.3 (0.5-1.1) mm in length * 0.5 +/- 0.3 (0.2-0.7)
      mm in width) in the testes causes their enlargement. Parasites cause destruction
      of the seminiferous tubule cells and complete loss of spermatozoa. Since
      spermatogenesis stops, this seems to be a form of "parasitic castration". This is
      the first known record of the genus Chloromyxum in amphibian testes.

PMID- 20680337
TI  - Toxoplasma gondii infection inhibits the mitochondrial apoptosis through
      induction of Bcl-2 and HSP70.
AB  - Heat-shock protein 70 (HSP70) is highly expressed in Toxoplasma gondii-infected
      cells. However, the role of this protein is not well understood, especially
      during apoptosis. This study addresses the mechanism behind the antiapoptotic
      chaperone activity of HSP70 in Toxoplasma-infected host cells using a human
      macrophage cell line, THP-1 by Western blot, DNA fragmentation assay,
      immunoprecipitation, and a caspase-3/7 activity assay based on cleavage of the
      colorimetric substrate DEVD-pNA. Apoptosis induced by arsenic trioxide
      (As(2)O(3)) was inhibited in T. gondii-infected THP-1 cells, but not in
      uninfected cells. Without As(2)O(3) induction of apoptosis, T. gondii infection
      caused increased expression of Bcl-2 and HSP70, but not caspase-3. However,
      active form caspase-3 levels were lower in As(2)O(3)-treated infected cells as
      compared with As(2)O(3)-treated uninfected cells. Bcl-2 expression in As(2)O(3)
      treated infected cells was similar to that in cells infected with T. gondii.
      Translocation of apoptosis-inducing factor (AIF) and release of cytochrome c from
      mitochondria were inhibited in As(2)O(3)-treated infected cells as compared with
      As(2)O(3)-treated uninfected cells. Increased parasite loads in Toxoplasma
      infected macrophages caused higher HSP70 and Bcl-2 expression in whole-cell
      extracts and fractionated components, respectively. However, expression of AIF
      and cytochrome c was unaffected. Toxoplasma dose-dependently inhibited caspase-3
      activation, thus revealing an anti-apoptotic parasite activity on cytochrome c
      mediated caspase activation in subcellular components. In addition,
      immunoprecipitation analysis suggested that HSP70 is capable of binding to the
      pro-apoptotic factors AIF and Apaf-1, but not to cytochrome c or procaspase-9.
      Taken together, these data demonstrate that T. gondii infection inhibits
      mitochondrial apoptosis through overproduction of anti-apoptotic Bcl-2 as well as
      HSP70, which are increased parasite loads dependently.

PMID- 20680338
TI  - Molecular characterization and expression of the MYND-ZF gene from Clonorchis
      sinensis.
AB  - The MYND-type zinc finger protein (MYND-ZF) is a large group of proteins
      containing the MYND domain which play an important role in protein-protein
      interactions. A cDNA clone encoding a novel MYND-ZF was isolated and identified
      from a Clonorchis sinensis (C. sinensis) adult cDNA library. The open reading
      frame of this novel cDNA sequence contains 1,440 base pairs with a putative
      protein of 479 amino acids showing a high homology with the MYND-ZF identified
      from other species. Recombinant CsMYND-ZF was expressed and purified from
      Escherichia coli BL21 (DE3). CsMYND-ZF transcripts were detected in the cDNA of
      adult worms and metacercariae but not in eggs of C. sinensis.
      Immunohistochemistry results revealed that CsMYND-ZF was deposited at the
      tegument of adult worms and metacercariae C. sinensis using anti-recombinant
      CsMYND-ZF serum. These findings may contribute to the development of a reliable
      diagnostic method.

PMID- 20680339
TI  - Development and laboratory evaluation of a lateral flow device (LFD) for the
      serodiagnosis of Theileria annulata infection.
AB  - Several DNA-based and serological tests have been established for the detection
      of Theileria annulata infection, including polymerase chain reaction, reverse
      line blot and loop-mediated isothermal amplification, indirect enzyme-linked
      immunosorbent assay (ELISA), and competitive ELISA. In this study, we have
      applied knowledge from the development and application of a recombinant protein
      based indirect ELISA and competitive ELISA to establish a rapid test for point-of
      care diagnosis of T. annulata infection in the field to be used by the
      veterinarian. For the development of a lateral flow test, the recombinantly
      expressed T. annulata surface protein (TaSP) was applied as the test antigen and
      anti-TaSP antiserum as the control line. TaSP antigen conjugated to colloidal
      gold particles was used as the detection system for visualization at the test
      line for the binding of anti-TaSP antibody present in the serum of infected
      animals. The developed test specifically detected antibodies in the serum of
      animals experimentally infected with T. annulata and showed no cross-reactivity
      with serum from animals infected with other tested bovine pathogens (Trypanosoma
      brucei, Anaplasma marginale, Babesia bigemina, Babesia bovis, and Theileria
      parva). Testing of field samples was compared to results obtained by other
      serological tests, resulting in a sensitivity and specificity of 96.3% and 87.5%
      compared to indirect fluorescence antibody test, 98.7% and 81.8% compared to
      indirect ELISA, and 100% and 47.6% compared to competitive ELISA. In conclusion,
      a rapid test for the detection of T. annulata infection (T. annulata lateral flow
      device, Ta-LFD) has been developed, which is easy to perform, delivers results to
      be read by the naked eye within 10 min, and is suitable for the detection of
      infection in field samples.

PMID- 20680340
TI  - Pathogenicity of some hypocrealean fungi to adult Aedes aegypti (Diptera:
      Culicidae).
AB  - The pathogenicity of 19 hypocrealean entomopathogenic fungi from seven different
      genera in adult Aedes aegypti was tested. All fungi proved to be pathogenic, and
      Isaria fumosorosea, Lecanicillium muscarium, Lecanicillium psalliotae,
      Metarhizium anisopliae, Metarhizium lepidiotae, Metarhizium majus, Metarhizium
      frigidum, Paecilomyces carneus, and Paecilomyces lilacinus caused total mortality
      within 15 days of exposure of mosquitoes to the fungal culture. All fungi
      developed on dead individuals. The high susceptibility of adults to most tested
      strains underlines the interest of entomopathogenic fungi-especially those of the
      genera Metarhizium, Isaria, Paecilomyces and Lecanicillium--for biological
      control of A. aegypti.

PMID- 20680341
TI  - Efficacy of nitroxynil against Fasciola hepatica resistant to triclabendazole in
      a naturally infected sheep flock.
AB  - The aim of this study was to compare the efficacy of triclabendazole (TCBZ) and
      nitroxynil against a TCBZ-resistant Fasciola hepatica strain in a naturally
      infected sheep flock. The efficacies were measured by the faecal egg count
      reduction test. The level of F. hepatica antigens was tested in faeces; and
      haematological indices such as total proteins (TP), albumin, hepatic enzymes and
      total IgG were also studied. The results confirmed the resistance of F. hepatica
      against TCBZ in the flock with an efficacy during the first month post-treatment
      between 59.4% and 73.8%. In the nitroxynil group, the efficacy during the same
      period ranged between 81.3% and 86%, likely because the efficacy of this drug
      against 7- to 9-week-old immature stages is only 50-90%. Anemia was showed in all
      groups and white blood cells were always higher than the reference range. The
      values of TP and albumin were within normal range in most of the sheep, and an
      increase in hepatic enzymes confirmed the liver damage. Regarding total IgG, some
      negative correlations were found with egg excretion, and in relation to the level
      of antigens in faeces, these ones decreased immediately after treatment. We
      conclude that nitroxynil could be an alternative in case of TCBZ resistance.

PMID- 20680342
TI  - Croton cajucara crude extract and isolated terpenes: activity on Trypanosoma
      cruzi.
AB  - Croton cajucara is a plant found in the Amazon region and is known for its
      medicinal properties. The effects of the methanolic extract of the stem bark of
      C. cajucara (MCC) and of the isolated terpenes, trans-dehydrocrotonin (t-DCTN)
      and acetyl aleuritolic acid (AAA), were investigated using four isolates of
      Trypanosoma cruzi. In assays with trypomastigotes, the extract was more active
      than the isolated compounds, presenting IC(50) in the range of 10 to 50 MUg/mL.
      The trypanocidal effect of MCC, AAA and benznidazole was significantly higher in
      the GLT291 and C45 strains, which were recently isolated from wild animals. MCC
      and AAA caused a dose-dependent inhibition of epimastigote proliferation. In
      assays using intracellular amastigotes, AAA and MCC reduced the percent of
      infection and the endocytic index after 96 h of treatment, at concentrations that
      were non-toxic to the host cells. MCC inhibited the trypanothione reductase
      pathway in both epimastigotes and trypomastigotes of all the subpopulations. The
      absence of AAA activity on the trypanothione reductase pathway in epimastigotes
      of Dm28c suggests heterogeneity of the biochemical profile between this clone and
      the three strains. Epimastigotes and trypomastigotes (GLT291) were treated for 24
      h with MCC or AAA, and both induced alterations of the plasma membrane, while AAA
      treated epimastigotes also displayed mitochondrial damage.

PMID- 20680343
TI  - Characterization and mRNA expression analysis of PI31, an endogenous proteasome
      inhibitor from Schistosoma mansoni.
AB  - The proline-rich inhibitor of 31 kDa (PI31) is highly conserved through metazoan
      evolution, and its activity in the proteasome inhibition is well-established
      although the precise mechanism of inhibition is unclear. The coding DNA sequence
      of Schistosoma mansoni PI31 (SmPI31) was cloned, and the recombinant protein was
      expressed in bacterial system. The correct amino acid sequence was confirmed by
      mass spectrometry and circular dichroism suggests that SmPI31 contains both alpha
      helix and non-structured regions. Inhibition assays, using the Suc-Leu-Leu-Val
      Tyr-4-MCA substrate for proteasome degradation, showed that the S. mansoni
      proteasome may be regulated by the inhibitory activity of SmPI31. A gene
      expression assay using qRT-PCR at various stages during the S. mansoni life cycle
      has shown that SmPI31 transcripts are expressed in all studied stages, suggesting
      that PI31 plays an important role during the developmental processes of the
      parasite. In this study first evidence is presented that PI31 has a conserved
      structure and plays a role as proteasome inhibitor in adult worms and it is
      expressed through life cycle.

PMID- 20680344
TI  - Molecular survey and genetic characterization of tick-borne pathogens in dogs in
      metropolitan Recife (north-eastern Brazil).
AB  - To identify DNA of the main tick-borne pathogens in dogs from Recife (Brazil),
      polymerase chain reactions were carried out on blood samples of dogs treated at
      the Veterinary Hospital of the Universidade Federal Rural de Pernambuco from
      March 2007 to June 2008. The detection of DNA was performed using specific
      primers. Amplicons were analyzed through electrophoresis and sequencing. A
      phylogenetic tree was constructed using the UPGMA method, revealing that the
      sequences were closely related to those of strains from other geographic regions.
      Among the 205 blood samples analyzed, 48.78% was positive for Anaplasma platys;
      38.04% was positive for Ehrlichia canis; 7.31% was positive for Babesia canis
      vogeli; and 0.49% was positive for Hepatozoon canis and Mycoplasma haemocanis.
      Coinfection of two or three pathogens was found in 23.9% (49/205) of the dogs.
      The subspecies B. canis vogeli was identified. Infection by H. canis and M.
      haemocanis is reported for the first time in dogs in the state of Pernambuco
      (Brazil). The data indicate that the main tick-borne pathogens in dogs in this
      region are E. canis and/or A. platys, followed by B. canis vogeli.

PMID- 20680345
TI  - Insights into the role of Toll-like receptors in modulation of T cell responses.
AB  - The innate immune receptors, such as Toll-like receptors (TLRs), are intimately
      involved in the early sensing of invading microorganisms or their structural
      components. Engagement of TLRs with their ligands results in activation of
      several downstream intracellular pathways leading to activation of innate and
      adaptive immune system cells. It was initially thought that TLRs are primarily
      expressed by antigen-presenting cells (APCs), such as macrophages and dendritic
      cells, and that interactions between microbial ligands and TLRs in these cells
      will indirectly result in activation of cells of the adaptive immune system,
      especially T cells. However, it has now become evident that TLRs are also
      expressed by various T cell subsets, such as conventional alphabetaT cells,
      regulatory T cells, and gammadeltaT cells as well as natural killer T cells.
      Importantly, it appears that at least in some of these T cell subsets, TLRs are
      functionally active, because stimulation of these cells with TLR agonists in the
      absence of APCs results in exertion of effector or regulatory functions of T
      cells. The present review attempts to summarize the recent findings related to
      TLR expression in different T cell subsets and the direct role of TLRs in the
      induction and regulation of T cell responses, including those responses that
      occur at mucosal surfaces. In addition, the potential use of TLR agonists for
      steering T cell responses as a prophylactic or therapeutic strategy in the
      context of infectious, allergic or autoimmune diseases is explored.

PMID- 20680346
TI  - Morphologic and transcriptomic comparison of adipose- and bone-marrow-derived
      porcine stem cells cultured in alginate hydrogels.
AB  - Advances in bioengineering, material chemistry, and developmental biology have
      led to the design of three-dimensional (3D) culture systems that better resemble
      the surrounding structure and chemistry of the in situ niches of cells in
      tissues. This study was designed to characterize and compare porcine adipose
      derived stem cells (ADSC) and bone-marrow-derived stem cells (BMSC) induced to
      differentiate toward osteogenic and adipogenic lineages in vitro by using a 3D
      alginate hydrogel. The morphology and gene expression of the two cell populations
      during differentiation were analyzed. Both ADSC and BMSC showed morphological
      evidence of osteogenic and adipogenic differentiation. Expression patterns of
      genes characteristic of the onset of osteogenic differentiation (ALP, COL1A1,
      SPARC, SPP1) were low at the beginning of culture and generally increased during
      the period of differentiation up to 28 days in culture. Expression of genes
      associated with adipogenic differentiation (ACSL1, ADFP, ADIPOQ, CD36, DBI,
      DGAT2, PPARG, SCD) was consistently increased in ADSC cultured in alginate
      hydrogel relative to the start of differentiation. However, adipogenic gene
      expression of BMSC cultured in alginate hydrogel was more limited when compared
      with that of ADSC. Evaluation of cell numbers (via the MTT staining assay)
      suggested a greater viability of BMSC under osteogenic conditions in alginate
      hydrogels than under adipogenic conditions, whereas ADSC had greater viability
      under adipogenic conditions than under osteogenic conditions. This study thus
      provides an important initial evaluation of ADSC and BMSC seeded and
      differentiated toward the osteogenic and adipogenic cell lineages in a 3D
      alginate hydrogel in vitro.

PMID- 20680347
TI  - Functional base of tongue fat injection in a patient with severe postradiation
      Dysphagia.
AB  - Lipofilling is a well-established technique in reconstructive plastic surgery. It
      is used primarily in recontouring of the body and face to correct post-traumatic
      and congenital defects. The regenerative properties of adipose tissue have
      allowed the use of the lipofilling technique for the treatment of burn sequelae
      and irradiated breast to improve tissue quality and elasticity. We report on the
      case of a patient treated with radiation therapy for a nasopharyngeal carcinoma
      who presented with severe postradiation dysphagia. The lipofilling technique was
      successfully used to improve abnormal swallowing. The technical details and
      functional outcomes are discussed.

PMID- 20680348
TI  - From evidence to a day-to-day laparoscopic colectomy.

PMID- 20680349
TI  - Band slippage and erosion after laparoscopic gastric banding: a meta-analysis.
AB  - BACKGROUND: Laparoscopic adjustable gastric banding has the lowest morbidity and
      mortality rates among the common bariatric procedures. Troublesome complications
      associated with this procedure include band slippage and erosion, often requiring
      revisionary surgery. Rates of slippage have decreased, and this appears to be due
      to changes in surgical technique. In the authors' experience, units with a low
      slippage rate also have a low erosion rate and vice versa. Thus a systematic
      review was undertaken to investigate this relationship. METHODS: Electronic
      databases were searched up to 31 December 2008. Publications focusing solely on
      laparoscopic adjustable gastric banding with at least 500 patients and a minimum
      follow-up period of 2 years were included in the study. Publications in languages
      other than English and those that failed to mention erosion and slippage rates
      were excluded. Multivariate meta-analyses were conducted separately for the pars
      flaccida group, the perigastric group, and the combined overall group to pool the
      average rates of both erosion and slippage for each paper included. The
      correlation between the occurrence rates for both erosion and slippage then was
      examined. RESULTS: The inclusion criteria were met by 19 studies. The mean rates
      of erosion and slippage were 1.03 and 4.93, respectively. The results
      demonstrated a statistically significant overall correlation between erosion and
      slippage rates (r = 0.48, p = 0.032). A very strong correlation between erosion
      and slippage was found if the perigastric technique of insertion was used (r =
      0.99, p < 0.001). However, this correlation was not statistically significant
      where the pars flaccida technique of insertion was used (r = 0.34, p = 0.38).
      CONCLUSIONS: The high correlation rate between erosion and slippage for the
      perigastric group strongly suggests that these complications share a common
      pathophysiology. This correlation is reduced with the pars flaccida technique,
      suggesting that perhaps a different etiology is associated with erosion in these
      studies. Surgical techniques that help to eliminate lap band slippage should also
      reduce rates of erosion.

PMID- 20680351
TI  - A novel CLCN5 mutation in a boy with Bartter-like syndrome and partial growth
      hormone deficiency.
AB  - Dent disease is an X-linked recessive disorder affecting the proximal tubule and
      is characterized by low-molecular-weight proteinuria (LMWP), hypercalciuria,
      nephrocalcinosis/nephrolithiasis with a variable number of features of Fanconi
      syndrome. It is most often associated with mutations in CLCN5, which encodes the
      endosomal electrogenic chloride/proton exchanger ClC-5. Renal acidification
      abnormalities are only rarely seen in Dent disease, whereas the hypokalemic
      metabolic alkalosis associated with hyperreninemic hyperaldosteronism (Bartter
      like syndrome) has been reported in only one patient so far. We report on a 5
      year-old boy with Dent disease caused by mutation in CLCN5 gene, c.1073G>A, who
      presented with hypokalemic metabolic alkalosis and hyperreninemic
      hyperaldosteronism persisting over the entire follow-up. No mutations were found
      in NKCC2, ROMK, NCCT, or ClC-Kb genes. In addition, the patient exhibited growth
      failure associated with partial growth hormone (GH) deficiency. Coexistence of
      Bartter-like syndrome features with LMWP should prompt a clinician to search for
      Dent disease. The Bartter syndrome phenotype seen in Dent disease patients may
      represent a distinct form of Bartter syndrome, the exact mechanism of which has
      yet to be fully elucidated. Growth delay that persists in spite of appropriate
      therapy should raise suspicion of other causes, such as GH deficiency.

PMID- 20680350
TI  - Fibrin glue for intraperitoneal laparoscopic mesh fixation: a comparative study
      in a swine model.
AB  - BACKGROUND: The classic method of mesh fixation in laparoscopic ventral hernia
      repair is transfascial sutures with tacks. This method has been associated with
      low recurrence rates, but yields significant morbidity from pain and bleeding.
      Fibrin glue has been used successfully in inguinal hernia repair with decreased
      incidence of chronic pain without an increase in recurrence rates, but its
      utility for laparoscopic ventral hernia repair is unknown. Our aim is to evaluate
      the efficacy of fibrin glue for laparoscopic mesh fixation to the anterior
      abdominal wall compared with other fixation methods. METHODS: Four different
      laparoscopic mesh fixation methods were randomly assigned to midline positions
      along the abdominal wall of 12 female pigs and compared: (1) fibrin glue only
      (GO), (2) transfascial sutures with tacks (ST), (3) fibrin glue with tacks (GT),
      and (4) tacks only (TO). At 4 weeks post implantation, tensile strength,
      adhesions, migration, contraction, and buckling/folding were assessed using
      Kruskal-Wallis one-way analysis by ranks test. RESULTS: There were no significant
      differences in tensile strength, adhesions or buckling/folding among the four
      fixation methods. A significant increase in mean migration (3.3 vs. 0.0 mm, p =
      0.03) and percentage contraction (28% vs. 14%, p = 0.02) were identified in the
      GO group when compared with ST (see Table 3). CONCLUSIONS: Mesh fixation using
      fibrin glue has comparable tensile strength and adhesion rate to sutures with
      tacks in the swine model. Increased contraction and migration rates associated
      with fibrin glue alone may be an issue and warrants further study. On the other
      hand, the GT group showed similar biomechanical characteristics to the other
      groups and may represent a reasonable alternative to the use of transfascial
      sutures.

PMID- 20680353
TI  - Social competence in childhood brain tumor survivors: a comprehensive review.
AB  - PURPOSE: To review the literature investigating the social competence outcomes of
      child and adolescent survivors of brain tumors. METHODS: Twenty articles
      published between 2000 and 2009 were accessed using PsycInfo and PubMed and
      reviewed for their findings related to three hypothesized levels of social
      competence (i.e., social adjustment, social performance, social skills). RESULTS:
      Current evidence indicates that childhood brain tumor survivors experience
      decreased social adjustment following treatment. Inconsistencies among studies
      continue to be an obstacle for advancing the field. The operationalization of
      social competence requires greater attention to facilitate comparability between
      studies (e.g., social adjustment, social performance, social skills). The effects
      of child, familial, and treatment factors and their relationships are still not
      well understood. There is a lack of theory driven research. CONCLUSIONS: Many
      childhood brain tumor survivors experience deficits in social competence at the
      level of social adjustment. These deficits worsen with time. Little is known
      about more rudimentary levels of social competence such as social skills or
      social performance. This information is needed to guide the development of social
      intervention programs.

PMID- 20680354
TI  - Characterization of cancer-induced bone pain: an exploratory study.
AB  - PURPOSE: Cancer-induced bone pain (CIBP) is the commonest cause of pain in
      patients with cancer. Its association with increased morbidity combined with
      limitations of currently available therapies makes it a clinical challenge.
      Clinical characterization of this complex pain syndrome is essential in
      underpinning clinical management and informing future research. The aim of this
      exploratory study was to characterise CIBP using self-rating scales. PATIENTS AND
      METHODS: A cross-sectional survey of patients with CIBP was carried out in a
      regional oncology centre. Patients described their pain over the preceding 24 h
      using the McGill Pain Questionnaire, Brief Pain Inventory (BPI), and a
      breakthrough pain questionnaire. Multiple linear regression analyses were
      conducted. RESULTS: Fifty-five patients were recruited. Annoying, gnawing,
      aching, and nagging were the most commonly used words to describe CIBP. From the
      BPI, median average pain was 4/10 and worst pain was 7/10 on a 0-10 Numerical
      Rating Scale. The worst pain score correlated more strongly with BPI interference
      score (p=0.001). Forty-one patients had breakthrough pain. Patients with
      breakthrough pain had higher total BPI interference scores than those with no
      breakthrough pain; median (IQR); 35.0 (2.5-44.7) vs. 18.5 (5.5-26.7), p<0.01. Of
      the patients, 20/41 (48%) had breakthrough pain of rapid onset (less than 5 min)
      and short duration (less than 15 min). CONCLUSION: In CIBP, worst pain most
      accurately reflects the characteristics of pain flares and functional impairment.
      Breakthrough pain is often unpredictable, sudden onset and short duration.
      Further characterization studies of CIBP in the broader cancer population are
      needed.

PMID- 20680355
TI  - Audit to monitor the uptake of national mouth care guidelines for children and
      young people being treated for cancer.
AB  - PURPOSE: The aim of this study is to review current oral care practices in
      children being treated for cancer against audit criteria derived from national
      guidelines, and to compare findings with data from a baseline survey carried out
      in 2002 prior to implementation of the national guidelines. METHODS: A telephone
      survey was carried out of all 21 haematology-oncology (HO) centres and seven bone
      marrow transplant (BMT) units within the UK Children's Cancer Study Group
      focusing on key audit themes of: availability of evidence-based guidelines, oral
      and dental care prior to and during cancer treatment, oral assessment, prevention
      and treatment of oral complications. RESULTS: The national guidelines were used
      in 19/25 (76%) settings that employed written guidelines. There was little
      variation in advice given to patients/parents on basic oral hygiene, and this
      advice was commensurate with guideline recommendations. Inconsistencies in oral
      care assessment, reported at baseline, remained commonplace across the majority
      of settings. In only 10/21 HO centres, it was usual practice for children to
      undergo dental assessment prior to commencing cancer treatment, indicating no
      improvement since baseline survey. Few therapies outside of the guideline
      recommendations were being used. The routine use of preventive nystatin, not
      recommended in the guideline, had significantly decreased from baseline (by 40%).
      CONCLUSIONS: Uptake of national guidelines by HO/BMT settings was good however
      certain oral care practices fell short of the guideline recommendations. Routine
      dental checks need to be embedded in practice. Further consideration is needed as
      to how oral assessment might be used more effectively in informing treatment.

PMID- 20680356
TI  - Acute emesis: moderately emetogenic chemotherapy.
AB  - This paper is a review of the recommendations for the prophylaxis of acute emesis
      induced by moderately emetogenic chemotherapy as concluded at the third Perugia
      Consensus Conference, which took place in June 2009. The review will focus on new
      studies appearing since the Second consensus conference in April 2004. The
      following issues will be addressed: dose and schedule of antiemetics, different
      groups of antiemetics such as corticosteroids, serotonin(3) receptor antagonists,
      dopamine(2) receptor antagonists, and neurokinin(1) receptor antagonists.
      Furthermore, antiemetic prophylaxis in patients receiving multiple cycles of
      moderately emetogenic chemotherapy will be reviewed. Consensus statements are
      given, including optimal dose and schedule of serotonin(3) receptor antagonists,
      dexamethasone, and neurokinin(1) receptor antagonists. The most significant
      recommendations (and changes since the 2004 version of the guidelines) are as
      follows: the best prophylaxis in patients receiving moderately emetogenic
      chemotherapy (not including a combination of an anthracycline plus
      cyclophosphamide) is the combination of palonosetron and dexamethasone on the day
      of chemotherapy, followed by dexamethasone on days 2-3. In patients receiving a
      combination of an anthracycline plus cyclophosphamide, a combination of a
      serotonin(3) receptor antagonist plus dexamethasone, plus the neurokinin(1)
      receptor antagonist aprepitant on the day of chemotherapy, followed by aprepitant
      days 2-3, is recommended.

PMID- 20680357
TI  - Weak habitat specificity in ectomycorrhizal communities associated with Salix
      herbacea and Salix polaris in alpine tundra.
AB  - This study explores mid-alpine ectomycorrhizal communities on Salix herbacea and
      Salix polaris in plant communities differing in nutrient status and snow
      conditions. Plant species were identified by tracking roots back to above ground
      structures while fungal species were identified using molecular methods. The
      fungi were identified to 34 molecular operational taxonomic units (MOTUs)/species
      but species accumulation curves indicated that the communities were only
      partially sampled. The estimated total species richness was 49 (+/-9 SD)
      MOTUs/species. No significant ectomycorrhizal community specificity was found
      between the two plant species and only weak specificity between different plant
      communities. Furthermore, no difference in proportion of colonized root tips
      could be demonstrated between plant communities. However, some fungal taxa showed
      tendencies to associate with specific environmental conditions. Sebacinaceae,
      Inocybe egenula, Russula cf. emetica, and a Tomentella sp. were found in meadow
      communities but not in the heath communities. Sistotrema cf. alboluteum and
      Tomentella cf. terrestris were only found in the dry and mesic heath communities.
      Classifications into exploration types showed that the contact type is more
      abundant in the dry heath community than the other communities. Cenococcum
      geophilum was the most common species but Cortinarius spp., Russula spp.,
      Tomentella spp., and Lactarius spp. were also common. This study confirms that
      alpine communities are rich in ectomycorrhizal fungi including species from a
      wide variety of fungal lineages and also show that many dominant species have
      wide ecological amplitude.

PMID- 20680358
TI  - Repeated administration of methamphetamine blocked cholecystokinin-octapeptide
      injection-induced c-fos mRNA expression without change in capsaicin-induced junD
      mRNA expression in rat cerebellum.
AB  - In the cerebellum, there are numerous cholecystokinin (CCK-8)-containing fibers.
      Since systemic CCK-8 injection-induced anxiety (psychological stress) activates
      the locus coeruleus cells that send mossy fiber inputs to the cerebellum, we
      examined whether systemic CCK-8 injections activate the rat and mouse cerebellum.
      First, injections of CCK-8 were found to induce c-fos mRNA expression in a vague
      patchy pattern that is different from single methamphetamine-induced Zebrin band
      like c-fos mRNA expression, suggesting that the CCK-8 activating mossy fibers
      induce gene expression differently from the dopamine-containing mossy fibers in
      the ventral tegmental area. Second, since CCK-8 facilitates neural activity of
      dopamine in the midbrain, we examined whether repeated methamphetamine
      administration that induced behavioral sensitization had similar effects on the
      cerebellar CCK system. Repeated administration of methamphetamine suppressed the
      CCK-8-induced c-fos mRNA expression in the rat cerebellum. Third, capsaicin
      injections (physical stress) into a hind limb of the rat increased junD mRNA
      expression with no effect on c-fos mRNA expression, and repeated methamphetamine
      injections had no effect on the capsaicin-induced expression of junD mRNA.
      Fourth, either single injection of methamphetamine or CCK-8 to mice increased c
      fos mRNA expression in the locus coeruleus, and so noradrenalin, but not
      dopamine, might interact with CCK-8-activating system. However, we considered the
      possibility unlikely. Thus, we conclude that repeated methamphetamine
      administration though dopamine selectively inhibits the c-fos mRNA expression
      after CCK-8 injection in the cerebellum.

PMID- 20680359
TI  - Molecular variation of hop mosaic virus isolates.
AB  - Hop mosaic virus (HpMV), a member of the genus Carlavirus, is importance to hop
      production worldwide. We identified variation in nucleic and amino acid sequences
      among 23 HpMV isolates from Australia, the USA, the Czech Republic, South Africa
      and Japan using a 1,455-bp fragment covering the 3' end of the virus genome
      including ORFs 4, 5 and 6. Three clusters of two or more isolates were identified
      in phylogenies of the total nucleotide sequence and the coat protein (ORF5) amino
      acid sequence. Two of these clusters combined in analyses of ORF4 and ORF6 amino
      acid sequences. Isolates from within and outside of Australia were found in each
      cluster, indicating that sequence variation was not associated with geographic
      source. Monitoring of HpMV variants in the field and evaluation of the impact of
      variants on vector association, rate of spread, and hop yield and quality can now
      be undertaken.

PMID- 20680360
TI  - Marek's disease virus microRNA designated Mdv1-pre-miR-M4 targets both cellular
      and viral genes.
AB  - Mdv1-miR-M4 is one of 25 microRNAs (miRNAs) expressed by Marek's disease virus
      (MDV-1), an oncogenic alphaherpesvirus that induces fatal T-cell lymphoma in
      chickens. Mdv1-miR-M4 was shown to be the second functional viral ortholog of miR
      155, a cellular miRNA that plays a crucial role in several physiological and
      pathological processes in lymphocyte biology. In this study, we investigated a
      panel of putative mdv1-miR-M4 targets involved in gene networks affecting both
      cellular and viral life cycles. Using luciferase reporter assays, we showed that
      mdv1-miR-M4-5P and miR-155 efficiently targeted a common set of 3' untranslated
      regions (3'UTR) of six cellular genes (GPM6B, RREB1, c-Myb, MAP3K7IP2, PU.1 and
      C/EBP). In addition, we also investigated the interactions between mdv1-miR-M4-5P
      and mdv1-miR-M43P and viral mRNAs encoding UL28 and UL32 in both reporter and
      western blot assays. Mdv1-miR-M4 specifically inhibited the translation of these
      two viral proteins, which are involved in the cleavage/packaging of herpesvirus
      DNA.

PMID- 20680361
TI  - Dual infection by cassava begomoviruses in two leguminous species (Fabaceae) in
      Yangambi, Northeastern Democratic Republic of Congo.
AB  - A study on cassava mosaic begomoviruses was conducted around Yangambi (DR Congo)
      by sampling 10 different leguminous species with or without symptoms similar to
      cassava mosaic disease. DNA was isolated to amplify CMBs using primers targeting
      AC2 and AC4 genes for virus detection by PCR. The results showed a dual infection
      by ACMV and EACMV in two weed species, Centrosema pubescens and Pueraria
      javanica, associated with mosaic symptoms. The DNA-A genome component of ACMV and
      EACMV from the infested weeds was sequenced. Seven ACMV and four EACMV isolates
      are reported. The major ACMV strains were closely related to ACMV-NGogo, ACMV-IC
      and ACMV-UGMld, whereas all EACMV strains were closely related to a Uganda
      variant, the most prevalent virus. This study shows that whiteflies may transmit
      CMBs to non-cassava plants under high epidemic pressure.

PMID- 20680362
TI  - Rapid detection of tobacco mosaic virus using the reverse transcription loop
      mediated isothermal amplification method.
AB  - Tobacco mosaic virus (TMV) can cause a severe disease that is capable of greatly
      reducing tobacco quality and yield. In this study, a one-step reverse
      transcription loop-mediated isothermal amplification (RT-LAMP) assay was
      developed for detection of TMV. The concentration of Mg(2+), reaction temperature
      and reaction time of the RT-LAMP were optimized to 5 mM, 65 degrees C, and 60
      min, respectively. The detection limit of the method was 100 times higher than
      that of RT-PCR. Visual inspection of RT-LAMP amplification demonstrated that
      positive and negative reactions exhibit distinctly different colours in daylight.
      Our results demonstrate that the method is stable, sensitive and specific.

PMID- 20680363
TI  - Postnatal care: a cross-cultural and historical perspective.
AB  - Childbirth and the immediate postpartum period represent a major transition in a
      woman's life. This period is considered a vulnerable time for the mother and
      child in most societies, and rituals for this transition are common. In this
      study, we present some examples of postpartum customs in a cross-cultural and
      historical perspective. Also, we present the current knowledge on the possible
      impact of postnatal care on mental health. Systematic literature searches were
      performed in Medline, PsycINFO, and the Science Citation Index Expanded (ISI) for
      the time period 1966 through May 2010. Reference lists in books on pregnancy and
      childbirth from the University Library in Oslo were used to obtain additional
      information. We found that the postnatal period seems to be universally defined
      as 40 days. Most cultures have special postnatal customs, including special diet,
      isolation, rest, and assistance for the mother. The uniformity of customs across
      different cultures is striking. However, many postnatal customs that were common
      before 1950 are no longer existent. The focus on rest and assistance for the
      mother after delivery has gradually decreased. Studies of associations of
      postnatal care and mental health in the mother are limited and show inconsistent
      results. More knowledge is needed on postnatal care and mental health.

PMID- 20680365
TI  - First principles calculations of the electronic and chemical properties of
      graphene, graphane, and graphene oxide.
AB  - The electrical and chemical properties of graphene (C(24)H(12)), graphane
      (C(24)H(24)) and graphene oxide (C(54)H(17)+O+(OH)(3)+COOH) were studied through
      the density functional theory (DFT) at level of Local Density Approximation (LDA)
      using a model C(n)H(m) like. The optimized geometry, energy gap and chemical
      reactivity for the proposed carbon 2D models are reported. It was found that
      while the graphene and graphane structures have semiconductor behavior, the
      graphene oxide behaves as semi-metal. However, a transition from semi-mental to
      semiconductor is predicted if the carboxyl group (COOH) is removed from such
      structure. The chemically active sites are analyzed on the basis of the
      electrophilic Fukui functions for each structure.

PMID- 20680364
TI  - Deficient maturation of aspects of attention and executive functions in early
      onset schizophrenia.
AB  - The few existing long-term, neuropsychological follow-up studies of early onset
      schizophrenia (EOS) patients have reported relative stability in some cognitive
      functions but abnormal developmental trajectories in verbal memory, set shifting,
      aspects of attention, and speed of information processing throughout late
      adolescence into early adulthood. The current 5-year follow-up study compared the
      development of specific cognitive functions in EOS patients (N = 17) from the
      time of first-episode to chronic phase with that of healthy controls (N = 38) and
      secondarily to patients with other early onset, non-organic, non-affective
      psychoses (EOP) (N = 11). Speed of processing of executive functions, set
      shifting, and attention improved significantly in the healthy controls and
      reflected continuous functional maturation during late adolescence and early
      adulthood. The developmental progression of attention and set shifting but not
      speed of processing of executive functions was significantly subnormal in EOS
      patients. Other specific cognitive functions that had attained functional
      maturity in the healthy controls before or around the time of the baseline
      assessment showed normal development in EOS patients during the follow-up period,
      indicating stable cognitive deficits. These results suggest post-onset
      developmental deficits in two out of the three aspects of attention and executive
      functions that have protracted maturational trajectories and that overlap the age
      of onset of EOS. No significant difference in the development of any specific
      cognitive function was found between the EOS and EOP group.

PMID- 20680366
TI  - A tricotage-like failure of nanographene.
AB  - The response of a nanographene sheet to external stresses was considered in terms
      of a mechanochemical reaction. The quantum chemical realization of the approach
      was based on the coordinate-of-reaction concept for the purpose of introducing a
      mechanochemical internal coordinate (MIC) that specifies a deformational mode.
      The related force of response is calculated as the energy gradient along the MIC,
      while the atomic configuration is optimized over all of the other coordinates
      under the MIC constant-pitch elongation. The approach is applied to the benzene
      molecule and (5,5) nanographene. A drastic anisotropy in the microscopic behavior
      of both objects under elongation along a MIC was observed when the MIC was
      oriented either along or normally to the C-C bond chain. Both the anisotropy and
      the high stiffness of the nanographene originate from the response of the
      benzenoid unit to stress.

PMID- 20680367
TI  - Prevalence of subtilase cytotoxin in verocytotoxin-producing Escherichia coli
      isolated from humans and raw meats in Belgium.
AB  - Recently, subtilase cytotoxin (SubAB) was detected in verocytotoxin-producing
      Escherichia coli (VTEC) that do not carry the Locus of Enterocyte Effacement
      (LEE) pathogenicity island. The distribution of the subA gene in VTEC isolated
      from patients with the hemolytic uremic syndrome, patients with diarrheal disease
      and raw meats from ruminants and wildlife in Belgium was investigated with PCR.
      The subA gene was detected more frequently (chi (2) = 10.2; d.f. = 1; P = 0.001)
      in VTEC from raw meats (10 of 87 strains) than in those from humans (8 of 274
      strains), and never in serogroups O157, O26, O103, O111 and O145. This virulence
      marker could play a role in the development of HUS after infection with LEE
      negative VTEC but was only found in one O178:H19 isolate out of 36 HUS-associated
      VTEC strains.

PMID- 20680368
TI  - In vitro and in vivo activities of linezolid alone and combined with vancomycin
      and imipenem against Staphylococcus aureus with reduced susceptibility to
      glycopeptides.
AB  - The objective of this study was to evaluate the in vitro and in vivo efficacies
      of linezolid (35 mg/kg/5 h), vancomycin (60 mg/kg/5 h), imipenem (30 mg/kg/5 h),
      linezolid+imipenem, linezolid+vancomycin and vancomycin+imipenem against two
      clinical Staphylococcus aureus isolates with reduced susceptibility to
      glycopeptides using time-kill curves and the murine peritonitis model. Time-kill
      curves were performed over 24 h. For the murine peritonitis model, peritonitis
      was induced by the intraperitoneal inoculation of 10(8) CFU/ml of each bacterial
      strain. Four hours later (0 h), the mice were randomly assigned to a control
      group or to therapeutic groups receiving subcutaneous treatment for 25 h.
      Bacterial counts in peritoneal fluid, bacteraemia and mortality rates were
      determined. The time-kill curves showed that the addition of linezolid to
      imipenem yielded synergistic results after 24 h. The addition of linezolid
      decreased vancomycin activity. In the animal model, vancomycin and linezolid
      monotherapies produced comparable bacterial decreases in mice infected with each
      strain but linezolid achieved higher rates of blood sterilisation. Linezolid
      tested either in monotherapy or in combination showed similar efficacy against
      both strains in terms of bacterial killing, number of negative blood cultures and
      survival. Linezolid and vancomycin were moderately bactericidal and similar in
      efficacy against glycopeptide-intermediate or -resistant S. aureus. Linezolid
      combinations, as effective as linezolid tested alone, could be considered as
      alternative options for the treatment of glycopeptide-intermediate S. aureus
      (GISA) infections.

PMID- 20680369
TI  - A systematic review on the effectiveness of pharmacological interventions for
      chronic non-specific low-back pain.
AB  - The objective of this review was to determine the effectiveness of
      pharmacological interventions [i.e., non-steroid anti-inflammatory drugs
      (NSAIDs), muscle relaxants, antidepressants, and opioids] for non-specific
      chronic low-back pain (LBP). Existing Cochrane reviews for the four interventions
      were screened for studies fulfilling the inclusion criteria. Then, the literature
      searches were updated. Only randomized controlled trials on adults (>=18 years)
      with chronic (>=12 weeks) non-specific LBP and evaluation of at least one of the
      main clinically relevant outcome measures (pain, functional status, perceived
      recovery, or return to work) were included. The GRADE approach was used to
      determine the quality of evidence. A total of 17 randomized controlled trials was
      included: NSAIDs (n = 4), antidepressants (n = 5), and opioids (n = 8). No
      studies were found for muscle relaxants; 14 studies had a low risk of bias. The
      studies only reported effects on the short term (<3 months). The overall quality
      of the evidence was low. NSAIDs and opioids seem to lead to a somewhat higher
      relief in pain on the short term, as compared to placebo, in patients with non
      specific chronic low back pain; opioids seem to have a small effect in improving
      function for a selection of patients who responded with an exacerbation of their
      symptoms after stopping their medication. However, both types of medication show
      more adverse effects than placebo. There seems to be no difference in effect
      between antidepressants and placebo in patients with non-specific chronic LBP.

PMID- 20680370
TI  - Reviewer's comment on "The 'X-Factor' Index: a new parameter for the assessment
      of the adolescent idiopathic scoliosis correction" by Yuqing Sun et al. (ESJO-D
      09-00493 R1).

PMID- 20680371
TI  - Recurrent scoliosis one year after surgical correction.
AB  - A year after anterolateral spondylodesis for progressive scoliosis, the patient
      showed a flexion gait pattern with recurrent deformity, due to late infection.
      Surgical debridement resolved all symptoms. Whereas most postoperative infections
      occur after posterior spondylodesis and present with back pain and mild increase
      of infection parameters, late infection after anterolateral approach is rare. In
      this case the patient did not present with the classic symptoms.

PMID- 20680372
TI  - Five-year outcome of surgical decompression of the lumbar spine without fusion.
AB  - As the average life expectancy of the population increases, surgical
      decompression of the lumbar spine is being performed with increasing frequency.
      It now constitutes the most common type of lumbar spinal surgery in older
      patients. The present prospective study examined the 5-year outcome of lumbar
      decompression surgery without fusion. The group comprised 159 patients undergoing
      decompression for degenerative spinal disorders who had been participants in a
      randomised controlled trial of post-operative rehabilitation that had shown no
      between-group differences at 2 years. Leg pain and back pain intensity (0-10
      graphic rating scale), self-rated disability (Roland Morris), global outcome of
      surgery (5-point Likert scale) and re-operation rates were assessed 5 years post
      operatively. Ten patients had died before the 5-year follow-up. Of the remaining
      149 patients, 143 returned a 5-year follow-up (FU) questionnaire (effective
      return rate excluding deaths, 96%). Their mean age was 64 (SD 11) years and
      92/143 (64%) were men. In the 5-year follow-up period, 34/143 patients (24%)
      underwent re-operation (17 further decompressions, 17 fusions and 1 intradural
      drainage/debridement). In patients who were not re-operated, leg pain decreased
      significantly (p < 0.05) from before surgery to 2 months FU, after which there
      was no significant change up to 5 years. Low back pain also decreased
      significantly by 2 months FU, but then showed a slight, but significant (p <
      0.05), gradual increase of <1 point by 5-year FU. Disability decreased
      significantly from pre-operative to 2 months FU and showed a further significant
      decrease at 5 months FU. Thereafter, it remained stable up to the 5-year FU. Pain
      and disability scores recorded after 5 years showed a significant correlation
      with those at earlier follow-ups (r = 0.53-0.82; p < 0.05). Patients who were re
      operated at some stage over the 5-year period showed significantly worse final
      outcomes for leg pain and disability (p < 0.05). In conclusion, pain and
      disability showed minimal change in the 5-year period after surgery, but the re
      operation rate was relatively high. Re-operation resulted in worse final outcomes
      in terms of leg pain and disability. At the 5-year follow-up, the "average"
      patient experienced frequent, but relatively low levels of, pain and moderate
      disability. This knowledge on the long-term outcome should be incorporated into
      the pre-operative patient information process.

PMID- 20680373
TI  - The severity of coronary atherosclerosis in diabetic and non-diabetic metabolic
      syndrome patients diagnosed according to different criteria and undergoing
      elective angiography.
AB  - Our aim in this study was to evaluate the relationship between metabolic syndrome
      (MS) as defined by different criteria and the severity of coronary lesions in a
      sample of diabetic and non-diabetic patients undergoing elective coronary
      angiography. All patients had blood and urine tests, physical examinations were
      performed before angiography, and finally they were classified based on three
      criteria (World Health Organisation-WHO, Adult Treatment Panel-ATP III and
      International Diabetes Federation-IDF). Eighty-eight patients were diabetic, and
      96 patients were non-diabetic. Among all patients, diabetics had significantly
      higher Gensini scores (P < 0.001). According to WHO criteria (P = 0.005) and IDF
      criteria (P = 0.015) metabolic syndrome patients had higher Gensini scores, but
      for ATP III criteria difference was not significant. When we evaluated diabetics
      and non-diabetics separately, non-diabetic patients with MS had significantly
      higher scores with WHO definition (P = 0.015) and mildly higher but not
      significant values with other MS criteria (P = 0.057 for both IDF and ATP III).
      Neither any one of MS components nor gender revealed significant relationship
      with coronary disease severity. In our study with a cohort of Turkish patients
      undergoing elective coronary angiography; we concluded that MS should be taken
      into consideration, especially in non-diabetic patients.

PMID- 20680374
TI  - Therapeutic drug monitoring of cyclosporine microemulsion in interstitial
      pneumonia with dermatomyositis.
AB  - The prognosis of dermatomyositis (DM)-associated progressive interstitial
      pneumonia (IP) has recently been improved by steroids/cyclosporine-A (CSA)
      combination therapy, but treatment outcomes varied. One reason for this variation
      is thought to be differences in CSA regimen. There is marked interpatient
      variability in CSA absorption. However, the pharmacokinetics of CSA has rarely
      been studied. In this study, we calculated the area under the blood concentration
      time curve (AUC) of CSA microemulsion in 15 patients with progressive IP
      complicating DM, and analyzed its correlation with CSA levels at blood sampling
      time points to investigate the optimum monitoring and dosing regimen. The highest
      correlation between AUC(0-6) and blood level of CSA was observed 2 h (C2) after
      drug administration (R = 0.910). The trough level (C0) was not correlated with
      AUC(0-6) (R = 0.052). There were no differences in blood levels (AUC(0-6), C2,
      and C6) between postprandial administration in a divided dose (CSA given twice
      daily) and preprandial administration once daily in a single dose, while C0 was
      significantly lower (P = 0.020) when the drug was administered once daily before
      breakfast. These findings suggest that measurement of CSA blood level, especially
      C2 and C0, is useful to monitor clinical and adverse effects of CSA during
      combination therapy. It is also suggested that preprandial, once daily
      administration of CSA is beneficial in DM patients with progressive IP.

PMID- 20680375
TI  - Churg-Strauss syndrome associated with elevated levels of serum interleukin-5 and
      T cell receptor-Cbeta gene rearrangement.
AB  - A 58-year-old woman was diagnosed with Churg-Strauss syndrome (CSS) based on the
      symptoms of bronchial asthma, eosinophilia, mononeuritis multiplex and
      histological examination of the right sural nerve. Prior to treatment, the serum
      interleukin (IL)-5 level was high, and rearrangement of the T cell receptor (TCR)
      gene was identified. This is the first report of TCR gene rearrangement in a
      patient with CSS. The expanded T cell clone may be responsible for the
      overproduction of IL-5. Further studies are warranted to disclose a prevalence of
      TCR gene rearrangement in CSS patients and its pathophysiological roles in the
      development of this disease.

PMID- 20680376
TI  - Successful management of systemic lupus erythematosus nephritis flare-up during
      pregnancy with tacrolimus.
AB  - Systemic lupus erythematosus (SLE) is one of the common autoimmune disorders that
      affect women during their childbearing years. Disease activity frequently
      increases during pregnancy and the postpartum period, representing a challenge
      for both the patient and the treating physician(s). We report a case of
      successful management of lupus nephritis flare in the first trimester. The
      patient developed bilateral leg edema and nephrotic-range proteinuria of 5 g/day.
      She was treated with steroids and tacrolimus, which resulted in the induction of
      remission during pregnancy. The patient reached full-term with no maternal or
      fetal complications. This case indicates that tacrolimus, which is convenient to
      use and has limited adverse effects, may represent a potential safe and effective
      treatment option for SLE nephritis during pregnancy.

PMID- 20680377
TI  - Development of myeloperoxidase-antineutrophil cytoplasmic antibody-associated
      renal vasculitis in a patient receiving treatment with anti-tumor necrosis factor
      alpha.
AB  - We report on a 33-year-old woman who presented with positive myeloperoxidase
      antineutrophil cytoplasmic antibody (MPO-ANCA) during rheumatoid arthritis
      treatment with infliximab. She had a history of worsening arthralgia, and
      urinalysis showed the new occurrence of hematuria and proteinuria. Renal biopsy
      showed necrotizing crescentic glomerulonephritis. Immunosuppressive therapy and
      discontinuation of the infliximab therapy alleviated her arthralgia and improved
      the urinalysis results. We report this rare case in which an anti-tumor necrosis
      factor-alpha (TNF-alpha) agent for ANCA-associated systemic vasculitis was
      studied.

PMID- 20680378
TI  - Clinical findings in parvovirus B19 infection in 30 adult patients in Kyoto.
AB  - To relate the clinical findings of parvovirus B19 infection to the phase of the
      disease, we performed a retrospective chart review of 30 adult patients who
      tested positive for IgM antibody against parvovirus B19 at our hospital from
      March 2003 to November 2008. Median patient age was 38 years, with 86.7% aged
      between 26 and 45 years. The male-to-female ratio was 4:26 (86.7% female).
      Symptoms in the first phase were mainly flu-like, including fever, headache, or
      myalgia. Symptoms in the second phase were arthralgia in 24 (85.7%) and rash in
      23 (82.1%). Fever was observed in 21 (70.0%), and 22 (75.9%) were found to be
      lymphopenic. The onsets in 73.3% of cases were concentrated within 10.1% of the
      study period, an observation nearly consistent with an outbreak of erythema
      infectiosum. Three patients had symmetrical swelling of joints, all of whom also
      had rash. Most patients visited the hospital within a week of onset and prognosis
      was favorable. In the parvovirus B19 infection, flu-like symptoms were frequent
      in the first phase, while rash and arthralgia were common in the second. Female
      sex, age between 26 and 45, and presence of rash, arthralgia, fever, and
      lymphopenia were clinical findings with a high frequency (>=70%), and these
      factors may contribute to diagnosis. In an era when early diagnosis and therapy
      is required in rheumatoid arthritis, it is important to recognize the parvovirus
      B19 infection with a presentation of acute arthritis and a favorable prognosis.

PMID- 20680379
TI  - Use of infliximab in a patient with pyoderma gangrenosum and rheumatoid
      arthritis.
AB  - Pyoderma gangrenosum (PG) is characterized by ulcerative skin lesions. Infliximab
      (IFX) may promote PG healing in patients with inflammatory bowel disease, but
      whether IFX is effective for treating PG in patients with rheumatoid arthritis
      (RA) has not reported. We report the case of a 53-year-old woman with PG
      complicated by RA who was treated using IFX therapy. This case suggests that IFX
      therapy might offer effective treatment for such patients.

PMID- 20680380
TI  - Electronic parameters for charge transfer along DNA.
AB  - We systematically examine all the tight-binding parameters pertinent to charge
      transfer along DNA. The pi molecular structure of the four DNA bases (adenine,
      thymine, cytosine, and guanine) is investigated by using the linear combination
      of atomic orbitals method with a recently introduced parametrization. The HOMO
      and LUMO wave functions and energies of DNA bases are discussed and then used for
      calculating the corresponding wave functions of the two B-DNA base-pairs (adenine
      thymine and guanine-cytosine). The obtained HOMO and LUMO energies of the bases
      are in good agreement with available experimental values. Our results are then
      used for estimating the complete set of charge transfer parameters between
      neighboring bases and also between successive base-pairs, considering all
      possible combinations between them, for both electrons and holes. The calculated
      microscopic quantities can be used in mesoscopic theoretical models of electron
      or hole transfer along the DNA double helix, as they provide the necessary
      parameters for a tight-binding phenomenological description based on the pi
      molecular overlap. We find that usually the hopping parameters for holes are
      higher in magnitude compared to the ones for electrons. Our findings are also
      compared with existing calculations from first principles.

PMID- 20680381
TI  - Novel mechanical properties in lamellar phases of liquid-crystalline diblock
      copolymers.
AB  - Structural properties of flexible nematic diblock copolymers in the lamellar
      phase are investigated using a mean-field model. We address two complementary
      questions on the mechanics of the system: 1) How does the nematic order affect
      the elasticity of the one-dimensional solid? 2) What effect does the block
      copolymer microstructure has on the orientation of the nematic director? In the
      limit when the microstructure does not influence the nematic director orientation
      we predict a soft lamellar compression mode. When the microstructure does
      influence the nematic director orientation, small compressions lead to
      conventional elasticity, until a critical strain is reached, where there is then
      a transition to a softer response. On the other hand, we show that an
      identifiable lamellar symmetry provides a direction along which the nematic
      director prefers to align. Our model provides avenues to explore nonlinear
      properties of flexible diblock copolymers in which the monomers on both sides
      have mesogenic side groups.

PMID- 20680382
TI  - The molecular basis of incomplete dominance at the A locus of CHS-D in the common
      morning glory, Ipomoea purpurea.
AB  - The mutable a(flaked (a(f)) allele at the A locus of the common morning glory
      (Ipomoea purpurea) confers incomplete dominance in flower pigmentation and is
      caused by insertion of the DNA transposon Tip100 into CHS-D, which encodes
      chalcone synthase and is required for anthocyanin biosynthesis. Levels of CHS-D
      transcripts, CHS-D protein, and anthocyanin pigment in heterozygous flowers were
      about half that in homozygous flowers, indicating that dosage-dependent
      expression of CHS-D is the primary cause of the observed incomplete dominance.
      This contrasts with the Nivea locus in snapdragon (Antirrhinum majus) in which
      incomplete dominance is caused by semi-dominant CHS alleles.

PMID- 20680383
TI  - Quantitative evaluation of patient movement during simulated acquisition of
      cephalometric radiographs.
AB  - The objective of this study was to perform the quantitative three-dimensional
      analysis of the patients' movements at the different time points during the
      simulated acquisition of cephalometric radiographs. Fifty-three subjects (32 men,
      21 women) were divided into four groups according to their age (Group 1: 9-12,
      Group 2: 13-19, Group 3: 20-25, and Group 4: 26-30 years old). The experiment
      (Exp) consisted in providing the subjects with three different kinds of verbal
      instructions as follows; Exp 1: they were simply instructed not to move, Exp 2:
      detailed instructions were provided, and Exp 3: they were specifically instructed
      to clench their molars. The amount of their movement during the 20 s of the
      cephalomatric X-ray exposure was measured using an optical marker and tracker.
      The maximum movement was analyzed three-dimensionally at 0.5, 2, 5, 10, 15, and
      20 s. There was minimal vibrating movement every 0.3-0.5 s and relatively large
      movement every 3-5 s. The youngest group showed the largest amount of movement
      among the four age groups, and their movement was more significant in the up and
      down direction (p < 0.05). There was no significant difference in the amount of
      movement according to the instructions. The longer exposure time showed the
      larger amount of the movement. Children can show the significant movements during
      X-ray taking, and the longer exposure time can also result in the larger movement
      during acquisition of cephalometric radiographs. Therefore, the shorter exposure
      time is recommended in order to improve image quality.

PMID- 20680384
TI  - An online evidence-based decision support system for distinguishing benign from
      malignant vertebral compression fractures by magnetic resonance imaging feature
      analysis.
AB  - Decision support systems have been used to promote the practice of evidence-based
      medicine. Computer-assisted diagnosis can serve as one element of evidence-based
      radiology. One area where such tools may provide benefit is analysis of vertebral
      compression fractures (VCFs), which can be a challenge in MRI interpretation.
      VCFs may be benign or malignant in etiology, and several MRI features may help to
      make this important distinction. We describe a web-based decision support system
      for discriminating benign from malignant VCFs as a prototype for a more general
      diagnostic decision support framework for radiologists. The system has three
      components: a feature checklist with an image gallery derived from proven
      reference cases, a prediction model, and a reporting mechanism. The website
      allows users to input the findings for a case to be interpreted using a
      structured feature checklist. The image gallery complements the checklist, for
      clarity and training purposes. The input from the checklist is then used to
      calculate the likelihood of malignancy by a logistic regression prediction model.
      Standardized report text is generated that summarizes pertinent positive and
      negative findings. This computer-assisted diagnosis system demonstrates the
      integration of three areas where diagnostic decision support can aid
      radiologists: first, in image interpretation, through feature checklists and
      illustrative image galleries; second, in feature-based prediction modeling; and
      third, in structured reporting. We present a diagnostic decision support tool
      that provides radiologists with evidence-based guidance for discriminating benign
      from malignant VCF. This model may be useful in other difficult-diagnosis
      situations and requires further clinical testing.

PMID- 20680385
TI  - The effect of ice water ingestion on autonomic modulation in healthy subjects.
AB  - OBJECTIVE: Drinking ice water is a common daily activity. The safety of ice water
      ingestion has been questioned due to its possible deleterious effect on heart
      rate or cardiac rhythm, especially in patients with acute myocardial infarction.
      Thus, we investigated the heart rate variability (HRV) before and after ice water
      ingestion in normal subjects to delineate the possible effect of ice water
      ingestion on autonomic nervous modulation. METHODS: Subjects were volunteers who
      came to the hospital to receive routine health examination. They were randomly
      assigned to drinking 250 ml of ice water or room temperature water. Twenty-eight
      subjects in the room temperature water ingestion group and 25 subjects in the ice
      water ingestion group were studied. The relationships between the change in HRV
      measures before and after water ingestion and clinical parameters were assessed
      by correlation analysis. RESULTS: After ice water ingestion, the percentage
      change in mean RR intervals (RRIs) (4 +/- 4 vs. -1 +/- 4, P < 0.001), standard
      deviation of RRIs (19 +/- 35 vs. 0 +/- 21, P = 0.018), high-frequency power (64
      +/- 90 vs. -3 +/- 41, P < 0.001), and normalized high-frequency power (39 +/- 99
      vs. -5 +/- 31, P = 0.038) were higher, while the percentage change in low-/high
      frequency power ratio (3 +/- 92 vs. 44 +/- 97, P = 0.017) was lower, when
      compared with those after the room temperature water ingestion. INTERPRETATION:
      Ice water ingestion can decrease heart rate through temperature stimulus-mediated
      vagal enhancement in healthy subjects.

PMID- 20680386
TI  - Strong potential for baroreflex-governed sympathetic outflow revealed during
      nausea.
AB  - Muscle sympathetic nerve activity (MSNA) was recorded in two patients with
      amyotrophic lateral sclerosis. As expected, they exhibited a high level of MSNA
      at rest, with an inverse weak response to different maneuvers normally eliciting
      strong increase in MSNA. About 30 min after the intake of a glucose solution,
      they developed nausea with an extreme rise in MSNA and blood pressure. In one
      patient, a quantified analysis of this reaction could be done: the outflow was
      close to 200% above the already high resting level and >100% stronger than the
      response to any of the performed maneuvers. We regard this observation of
      importance, because it seems to unveil resources utilized only rarely, and
      strongly overcoming the "ceiling effect" that seemingly is a hindrance for
      sympathetic activation in subjects with high lever of MSNA at rest. An inhibitory
      "safety limit" might exist, the trespassing of which would damage the organism
      and thus occurs only during extraordinary circumstances.

PMID- 20680388
TI  - Efficiency of nonhomologous DNA end joining varies among somatic tissues, despite
      similarity in mechanism.
AB  - Failure to repair DNA double-strand breaks (DSBs) can lead to cell death or
      cancer. Although nonhomologous end joining (NHEJ) has been studied extensively in
      mammals, little is known about it in primary tissues. Using oligomeric DNA
      mimicking endogenous DSBs, NHEJ in cell-free extracts of rat tissues were
      studied. Results show that efficiency of NHEJ is highest in lungs compared to
      other somatic tissues. DSBs with compatible and blunt ends joined without
      modifications, while noncompatible ends joined with minimal alterations in lungs
      and testes. Thymus exhibited elevated joining, followed by brain and spleen,
      which could be correlated with NHEJ gene expression. However, NHEJ efficiency was
      poor in terminally differentiated organs like heart, kidney and liver.
      Strikingly, NHEJ junctions from these tissues also showed extensive deletions and
      insertions. Hence, for the first time, we show that despite mode of joining being
      generally comparable, efficiency of NHEJ varies among primary tissues of mammals.

PMID- 20680389
TI  - RNA interference pathways in filamentous fungi.
AB  - RNA interference is a conserved homology-dependent post
      transcriptional/transcriptional gene silencing mechanism in eukaryotes. The
      filamentous fungus Neurospora crassa is one of the first organisms used for RNAi
      studies. Quelling and meiotic silencing by unpaired DNA are two RNAi-related
      phenomena discovered in Neurospora, and their characterizations have contributed
      significantly to our understanding of RNAi mechanisms in eukaryotes. A type of
      DNA damage-induced small RNA, microRNA-like small RNAs and Dicer-independent
      small silencing RNAs were recently discovered in Neurospora. In addition, there
      are at least six different pathways responsible for the production of these small
      RNAs, establishing this fungus as an important model system to study small RNA
      function and biogenesis. The studies in Cryphonectria, Mucor, Aspergillus and
      other species indicate that RNAi is widely conserved in filamentous fungi and
      plays important roles in genome defense. This review summarizes our current
      understanding of RNAi pathways in filamentous fungi.

PMID- 20680391
TI  - Modulation of IL-2 expression after uptake of hepatitis C virus non-enveloped
      capsid-like particles: the role of p38 kinase.
AB  - Hepatitis C virus (HCV) has been shown to actively replicate in cells of the
      immune system, altering both their function and cytokine expression. Naked
      nucleocapsids have been reported in the serum of infected patients. We
      investigated interference of recombinant non-enveloped capsid-like particles with
      signaling pathways in T cells. HCV non-enveloped particles (HCVne)
      internalization was verified in Jurkat and Hut 78 T cells, as well as primary
      human peripheral blood and intrahepatic mononuclear cells. HCVne uptake leads to
      activation of the MAPKs-p38 signaling pathway. Using specific phosphoantibodies,
      signaling pathways inhibitors, and chemical agents, it was demonstrated that p38
      activation in T cells correlated with IL-2 transcriptional activation and was
      accompanied by a parallel increase of IL-2 cytokine secretion. c-fos and egr-1,
      two transcription factors, essential for IL-2 promoter activity, were also found
      to be elevated. We propose that HCVne uptake by T lymphocytes results in
      increased MAPKs-p38 activity and IL-2 expression, thus altering the host immune
      response.

PMID- 20680390
TI  - Interactions of the proteins of neuronal ceroid lipofuscinosis: clues to
      function.
AB  - Neuronal ceroid lipofuscinoses (NCL) are caused by mutations in eight different
      genes, are characterized by lysosomal accumulation of autofluorescent storage
      material, and result in a disease that causes degeneration of the central nervous
      system (CNS). Although functions are defined for some of the soluble proteins
      that are defective in NCL (cathepsin D, PPT1, and TPP1), the primary function of
      the other proteins defective in NCLs (CLN3, CLN5, CLN6, CLN7, and CLN8) remain
      poorly defined. Understanding the localization and network of interactions for
      these proteins can offer clues as to the function of the NCL proteins and also
      the pathways that will be disrupted in their absence. Here, we present a review
      of the current understanding of the localization, interactions, and function of
      the proteins associated with NCL.

PMID- 20680394
TI  - Adapting to the impacts of climate change on food security among Inuit in the
      Western Canadian Arctic.
AB  - This study examined critical impacts of climate change on Inuit diet and
      nutritional health in four Inuit communities in the Inuvialuit Settlement Region,
      Western Arctic, Canada. The first objective was to combine data from community
      observation studies and dietary interview studies to determine potential climate
      change impacts on nutritional quality. The second objective was to address the
      scale of data collection and/or availability to compare local versus regional
      trends, and identify implications for adaptation planning. Information was
      compiled from 5 reports (4 community reports and 1 synthesis report) of climate
      change observations, impacts and adaptations in 12 Inuit communities (2005-2006),
      and from a dietary report of food use from 18 Inuit communities (1997-2000).
      Changing access to, availability of, quality of, and ability to use traditional
      food resources has implications for quality of diet. Nutritional implications of
      lower traditional food use include likely reductions in iron, zinc, protein,
      vitamin D, and omega-3 fatty acids, among others. The vulnerability of each
      community to changing food security is differentially influenced by a range of
      factors, including current harvesting trends, levels of reliance on individual
      species, opportunities for access to other traditional food species, and exposure
      to climate change hazards. Understanding linkages between climate change and
      traditional food security provides a basis for strengthening adaptive capacity
      and determining effective adaptation options to respond to future change.

PMID- 20680392
TI  - Deciphering the complexity of Toll-like receptor signaling.
AB  - Toll-like receptors (TLRs) are essential players in the innate immune response to
      invading pathogens. Although extensive research efforts have provided a
      considerable wealth of information on how TLRs function, substantial gaps in our
      knowledge still prevent the definition of a complete picture of TLR signaling.
      However, several recent studies describe additional layers of complexity in the
      regulation of TLR ligand recognition, adaptor recruitment, posttranslational
      modifications of signaling proteins, and the newly described, autonomous role of
      the TLR4 co-receptor CD14. In this review, by using it as model system for the
      whole TLR family, we attempt to provide a complete description of the signal
      transduction pathways triggered by TLR4, with a particular emphasis on the
      molecular and cell biological aspects regulating its function. Finally, we
      discuss a recently reported model of CD14-dependent signaling and highlight its
      biological implications.

PMID- 20680393
TI  - Protein deacetylation by sirtuins: delineating a post-translational regulatory
      program responsive to nutrient and redox stressors.
AB  - Lysine acetylation/deacetylation is increasingly being recognized as common post
      translational modification that appears to be broadly operational throughout the
      cell. The functional roles of these modifications, outside of the nucleus, have
      not been extensively studied. Moreover, as acetyl-CoA donates the acetyl group
      for acetylation, nutrient availability and energetic status may be pivotal in
      this modification. Similarly, nutrient limitation is associated with the
      deacetylation reaction. This modification is orchestrated by a novel family of
      sirtuin deacetylases that function in a nutrient and redox dependent manner and
      targets non-histone protein deacetylation. In compartment-specific locations,
      candidate target proteins undergoing lysine-residue deacetylation are being
      identified. Through these investigations, the functional role of this post
      translational modification is being delineated. We review the sirtuin family
      proteins, discuss their functional effects on target proteins, and postulate on
      potential biological programs and disease processes that may be modified by
      sirtuin-mediated deacetylation of target proteins.

PMID- 20680395
TI  - Transmission dynamics of highly pathogenic avian influenza at Lake Constance
      (Europe) during the outbreak of winter 2005-2006.
AB  - Highly pathogenic avian influenza virus (HPAI) H5N1 poses a serious threat to
      domestic animals. Despite the large number of studies on influenza A virus in
      waterbirds, little is still known about the transmission dynamics, including
      prevalence, behavior, and spread of these viruses in the wild waterbird
      population. From January to April 2006, the HPAI H5N1 virus was confirmed in 82
      dead wild waterbirds at the shores of Lake Constance. In this study, we present
      simple mathematical models to examine this outbreak and to investigate the
      transmission dynamics of HPAI in wild waterbirds. The population dynamics model
      of wintering birds was best represented by a sinusoidal function. This model was
      considered the most adequate to represent the susceptible compartment of the SIR
      model. The three transmission models predict a basic reproduction ratio (R (0))
      with value of approximately 1.6, indicating a small epidemic, which ended with
      the migration of susceptible wild waterbirds at the end of the winter. With this
      study, we quantify for the first time the transmission of HPAI H5N1 virus at Lake
      Constance during the outbreak of winter 2005-2006. It is a step toward the
      improvement of the knowledge of transmission of the virus among wild waterbirds.

PMID- 20680396
TI  - Unexpected late radiation neurotoxicity following bevacizumab use: a case series.
AB  - The purpose of this case series is to report the unexpected occurrence of four
      cases of late radiation-induced neurotoxicity with bevacizumab use following
      radiotherapy to the CNS. We retrospectively reviewed the case records of four
      patients, three with glioblastoma and one with bone metastases secondary to
      metastatic breast cancer, who were treated with radiotherapy and developed late
      radiation-induced neurotoxicity following bevacizumab use. Three cases of optic
      neuropathy in glioblastoma patients and a single case of Brown-Sequard syndrome
      in the thoracic spine of a patient with metastatic breast cancer are reported. We
      hypothesize that bevacizumab use following radiotherapy to the CNS may inhibit
      vascular endothelial growth factor-dependent repair of normal neural tissue, and
      thus may increase the risk of late radiation neurotoxicity. Phase III data on the
      safety and efficacy of bevacizumab use with radiation in the setting of
      glioblastoma is awaited.

PMID- 20680397
TI  - Recurrent spinal cord glioblastoma: salvage therapy with bevacizumab.
AB  - Primary spinal cord tumors constitute 2-4% of all primary central nervous system
      malignancies in adults of which less than 5% are glioblastoma. A retrospective
      evaluation to determine toxicity and response to bevacizumab in patients with
      recurrent spinal cord glioblastoma. Six patients (4 males; 2 females: median age
      34 years) with recurrent spinal cord glioblastoma were treated with bevacizumab
      (10 mg/kg given once every 2 weeks wherein 2 treatments constituted a cycle of
      therapy). All patients had failed surgery and temozolomide-based
      chemoradiotherapy and post-radiotherapy temozolomide. Blood counts, chemistry
      panel, urine protein to creatinine ratio and neurologic examination were obtained
      bi-weekly. Contrast-enhanced spine MRI was performed after one cycle of therapy
      and thereafter following every two cycles of bevacizumab. Treatment-related
      complications included fatigue in six patients, constipation in 4, hypertension
      in 2, venous thrombosis in 2, and infection without neutropenia in 2. There were
      three grade 3 toxicities (1 each fatigue, leukopenia and venous thrombosis).
      There were no treatment-related deaths. After one cycle of bevacizumab, one
      patient (17%) demonstrated progressive disease, 2 (34%) partial responses and
      three (51%) stable disease. Overall median response or stable disease duration
      (disease free progression) was 7 months (range 3-11 months). Overall median
      survival was 9 months (range of 5-13 months). Bevacizumab is well tolerated, has
      tolerable toxicity and apparent activity in this small cohort of adults with
      recurrent spinal cord glioblastoma.

PMID- 20680398
TI  - Inhibition of Necl-5 (CD155/PVR) reduces glioblastoma dispersal and decreases MMP
      2 expression and activity.
AB  - Patients afflicted with glioblastoma (GBM) have poor survival due to dispersive
      invasion throughout the brain. Necl-5, a cell surface receptor for vitronectin,
      is expressed in GBM but not normal brain. In several GBM cell lines Necl-5
      promotes migration and invasion but the mechanism is poorly understood. In this
      study, we show that knockdown of Necl-5 by RNAi results in markedly decreased
      invasion of A172 GBM cells in a 3-dimensional matrix. There is a concomitant
      decrease in the expression and activity of matrix metalloproteinase-2 (MMP-2), a
      known factor in GBM invasion and disease severity. Knockdown of Necl-5 diminishes
      basal activation of Akt, an established mediator of MMP-2 expression in gliomas.
      Knockdown of Necl-5 also limits the maximal Akt activation in response to
      vitronectin, which requires the activity of Integrin-linked kinase (ILK). During
      migration, Necl-5, Akt and ILK co-localize at focal contacts at the leading edge
      of the plasma membrane, suggesting that these molecules may act to integrate Akt
      signaling at the leading edge to induce MMP-2 expression. By virtue of its
      restricted expression in GBM and its role in invasion, Necl-5 may be an
      attractive target for limiting MMP-2 production in glioblastoma, and therefore
      limiting dispersal.

PMID- 20680399
TI  - Tumor vascular leakiness and blood volume estimates in oligodendrogliomas using
      perfusion CT: an analysis of perfusion parameters helping further characterize
      genetic subtypes as well as differentiate from astroglial tumors.
AB  - The purpose of this study was to determine the usefulness of perfusion CT (PCT)
      parameters particularly blood volume and neovascular permeability estimates
      (permeability surface area-product, PS) in the evaluation of oligodendrogliomas
      (OG), correlation with genetic subtypes of OGs (with or without loss of
      heterozygosity/LOH on 1p/19q) as well as comparison of perfusion parameters of
      OGs with astroglial tumors. Pre-operative PCT done in 21 patients with OGs was
      retrospectively correlated with our previously published PCT data for 32 patients
      with astroglial neoplasms (Jain R et al., AJNR Am J Neuroradiol 29:694-700,
      2008). All OGs were also analyzed for genetic subtypes of with or without LOH.
      PCT parameters PS and cerebral blood volume (CBV) were obtained for the entire
      lesion and a statistical analysis done to correlate various histopathological
      variants. Low grade OGs (n = 13) showed slightly lower CBV (1.42 vs. 1.72 ml/100
      g; P value 0.391) and PS (0.56 vs. 0.95 ml/100 g/min; P value 0.099) as compared
      to high grade OGs (n = 8), though not statistically significant. LOH positive OGs
      (n = 13) showed higher mean CBV (1.59 vs. 1.45; P value 0.712) and slightly lower
      PS (0.68 vs. 0.75; P value 0.718) as compared to LOH negative OGs (n = 8),
      although not statistically significant. Low grade OGs (n = 13) showed higher mean
      CBV 1.42 ml/100 g as compared to low grade astroglial tumors (n = 8) 0.95 ml/100
      g (P value = 0.08), however no statistically significant difference was noted for
      PS (0.56 vs. 0.52 ml/100 g/min, P value 0.695). Statistically significant
      differences were observed in CBV and PS values of high grade OGs and high grade
      astroglial tumors with the high grade glial tumors showing higher mean CBV (2.79
      vs. 1.72; P value 0.03) as well as higher PS (2.37 vs. 0.95; P value < 0.01),
      however this difference was not significant if only comparing grade III OGs with
      grade III astroglial tumors. PCT perfusion parameters including PS values do not
      help grade OGs despite showing a trend for higher CBV and PS in higher grade OGs.
      Similarly LOH positive OGs also showed slightly higher CBV, but again failed to
      reach any statistically significant level. Low grade OGs showed slightly higher
      CBV as compared to low grade astroglial tumors, whereas higher grade OGs showed
      significantly lower PS values as compared to higher grade astroglial tumors
      despite showing high CBV.

PMID- 20680400
TI  - hHSS1: a novel secreted factor and suppressor of glioma growth located at
      chromosome 19q13.33.
AB  - The completion of the Human Genome Project resulted in discovery of many unknown
      novel genes. This feat paved the way for the future development of novel
      therapeutics for the treatment of human disease based on novel biological
      functions and pathways. Towards this aim, we undertook a bioinformatics analysis
      of in-house microarray data derived from purified hematopoietic stem cell
      populations. This effort led to the discovery of HSS1 (Hematopoietic Signal
      peptide-containing Secreted 1) and its splice variant HSM1 (Hematopoietic Signal
      peptide-containing Membrane domain-containing 1). HSS1 gene is evolutionarily
      conserved across species, phyla and even kingdoms, including mammals,
      invertebrates and plants. Structural analysis showed no homology between HSS1 and
      known proteins or known protein domains, indicating that it was a truly novel
      protein. Interestingly, the human HSS1 (hHSS1) gene is located at chromosome
      19q13.33, a genomic region implicated in various cancers, including malignant
      glioma. Stable expression of hHSS1 in glioma-derived A172 and U87 cell lines
      greatly reduced their proliferation rates compared to mock-transfected cells.
      hHSS1 expression significantly affected the malignant phenotype of U87 cells both
      in vitro and in vivo. Further, preliminary immunohistochemical analysis revealed
      an increase in hHSS1/HSM1 immunoreactivity in two out of four high-grade
      astrocytomas (glioblastoma multiforme, WHO IV) as compared to low expression in
      all four low-grade diffuse astrocytomas (WHO grade II). High-expression of hHSS1
      in high-grade gliomas was further supported by microarray data, which indicated
      that mesenchymal subclass gliomas exclusively up-regulated hHSS1. Our data reveal
      that HSS1 is a truly novel protein defining a new class of secreted factors, and
      that it may have an important role in cancer, particularly glioma.

PMID- 20680401
TI  - Straightforward and complete deposition of NMR data to the PDBe.
AB  - We present a suite of software for the complete and easy deposition of NMR data
      to the PDB and BMRB. This suite uses the CCPN framework and introduces a freely
      downloadable, graphical desktop application called CcpNmr Entry Completion
      Interface (ECI) for the secure editing of experimental information and associated
      datasets through the lifetime of an NMR project. CCPN projects can be created
      within the CcpNmr Analysis software or by importing existing NMR data files using
      the CcpNmr FormatConverter. After further data entry and checking with the ECI,
      the project can then be rapidly deposited to the PDBe using AutoDep, or exported
      as a complete deposition NMR-STAR file. In full CCPN projects created with ECI,
      it is straightforward to select chemical shift lists, restraint data sets,
      structural ensembles and all relevant associated experimental collection details,
      which all are or will become mandatory when depositing to the PDB. Instructions
      and download information for the ECI are available from the PDBe web site at
      http://www.ebi.ac.uk/pdbe/nmr/deposition/eci.html .

PMID- 20680402
TI  - Mapping of protein structural ensembles by chemical shifts.
AB  - Applying the chemical shift prediction programs SHIFTX and SHIFTS to a data base
      of protein structures with known chemical shifts we show that the averaged
      chemical shifts predicted from the structural ensembles explain better the
      experimental data than the lowest energy structures. This is in agreement with
      the fact that proteins in solution occur in multiple conformational states in
      fast exchange on the chemical shift time scale. However, in contrast to the real
      conditions in solution at ambient temperatures, the standard NMR structural
      calculation methods as well chemical shift prediction methods are optimized to
      predict the lowest energy ground state structure that is only weakly populated at
      physiological temperatures. An analysis of the data shows that a chemical shift
      prediction can be used as measure to define the minimum size of the structural
      bundle required for a faithful description of the structural ensemble.

PMID- 20680403
TI  - Increased platelet, leukocyte and endothelial microparticles predict enhanced
      coagulation and vascular inflammation in pulmonary hypertension.
AB  - Pulmonary hypertension (PH) is associated with platelet activation, vascular
      inflammation and endothelial dysfunction leading to often life threatening
      thrombo-embolic complications. Microparticles (MPs) are cell vesicles with strong
      coagulatory and inflammatory effects being released during cell activation and
      apoptosis. As there are currently no established surrogate markers predicting
      platelet activation and pro-coagulation in PH patients, the aim of the study was
      to analyze different pro-coagulatory MP populations that might be related to
      thrombo-embolic complications in PH patients. Circulating MPs from platelet-
      (PMP, CD31(+)/61(+)), leukocyte- (LMP, CD11b(+)) and endothelial- (EMP, CD62E(+))
      origin were measured by flow cytometry in 19 PH patients and were compared to 16
      controls. PH patients had increased levels of PMP (PH vs. control 1,016 +/- 201
      vs. 527 +/- 59 counts per min [cpm], P = 0.032), LMP (PH vs. control 31 +/- 3 cpm
      vs. 18 +/- 2 cpm, P = 0.001) and EMP (PH vs. control 99 +/- 14 cpm vs. 46 +/- 6
      cpm, P = 0.001). Furthermore, PMP correlated to LMP (PMP vs. LMP: r = 0.75, P <
      0.001) and LMP correlated to EMP levels (LMP vs. EMP, r = 0.74, P < 0.001)
      indicating a functional interaction between the different types of MP. In
      comparison to non-embolic PH patients, patients with a thrombo-embolic PH
      suffered from enhanced endothelial cell dysfunction as represented by
      significantly increased EMP levels (thrombo-embolic PH vs. non-embolic PH 137 +/-
      27 vs. 72 +/- 10, P = 0.02). PH patients have increased levels of platelet-,
      leukocyte- and endothelial MP indicating an increased vascular pro-coagulation
      and inflammation which might be related to thrombo-embolic complications as well
      as PH progression.

PMID- 20680404
TI  - Distribution of 45S and 5S rDNA sites in 23 species of Eleocharis (Cyperaceae).
AB  - Studies of rDNA location in holocentric chromosomes of the Cyperaceae are scarce,
      but a few reports have indicated the occurrence of multiple 45S rDNA sites at
      terminal positions, and in the decondensed state of these regions in
      prometaphase/metaphase. To extend our knowledge of the number 45S and 5S rDNA
      sites and distribution in holocentric chromosomes of the Cyperaceae, 23 Brazilian
      species of Eleocharis were studied. FISH showed 45S rDNA signals always located
      in terminal regions, which varied from two (E. bonariensis with 2n = 20) to ten
      (E. flavescens with 2n = 10 and E. laeviglumis with 2n = 60). 5S rDNA showed less
      variation, with 16 species exhibiting two sites and 7 species four sites,
      preferentially at terminal positions, except for four species (E. subarticulata,
      E. flavescens, E. sellowiana and E. geniculata) that showed interstitial sites.
      The results are discussed in order to understand the predominance of terminal
      rDNA sites, the mechanisms involved in the interstitial positioning of 5S rDNA
      sites in some species, and the events of amplification and dispersion of 45S rDNA
      terminal sites.

PMID- 20680405
TI  - Confounding from cryptic relatedness in haplotype-based association studies.
AB  - Cryptic relatedness was suggested to be an important source of confounding in
      population-based association studies (PBAS). The impact of cryptic relatedness on
      the performance of haplotype phase inference and haplotype-based association
      tests is not clear. In this study, we used the Hapmap genetic data to simulate a
      set of related samples. We evaluated the accuracy of haplotype phase inferred by
      PHASE 2.1 and calculated the power, type I error rates, accuracy and positive
      prediction value (PPV) of haplotype frequency-based association tests (HFAT) and
      haplotype similarity-based association tests (HSAT) under various scenarios,
      considering relatedness levels, disease models and sample sizes. Cryptic
      relatedness appeared to slightly increase the accuracy of haplotype phase
      inference. We observed significant negative effect of cryptic relatedness on the
      performance of HFAT and HSAT. Ignoring cryptic relatedness may increase spurious
      association results in haplotype-based PBAS.

PMID- 20680406
TI  - Radiation hazard assessment in Egyptian painting oxides. A comparative study.
AB  - Building materials are potential sources of radiation, which represents a risk
      factor for human disease including cancer. In this work, the natural
      radioactivity due to the presence of (238)U, (226)Ra, (232)Th and (40)K in
      different painting oxides has been measured using gamma spectrometry with a Hyper
      Pure germanium detector. The concentrations of the heavy metals (Cd, Co, Mn, Pb,
      Ni, Sr, Rb, Cr, Cu and Zn) were determined by atomic absorption spectrometry in
      order to investigate their possible correlation with radioactive elements. The
      activity concentrations of (238)U, (226)Ra, (232)Th and (40)K ranged from 15 +/-
      0.75 to 126 +/- 14, 2.35 +/- 0.09 to 72.96 +/- 1.96, 1.76 +/- 0.31 to 12.88 +/-
      0.7 and 2.26 +/- 0.09 to 200 +/- 3.34 Bq kg(-1), respectively. The calculated
      radium-equivalents were lower than values recommended for construction materials
      (370 Bq kg(-1)). The absorbed dose rates due to the natural radioactivity of the
      investigated samples ranged from 8.11 +/- 0.24 to 68.46 +/- 4.20 nGy/h. Also, the
      results revealed that some heavy metals (Cd, Co, Mn and Rb) were correlated with
      (238)U, (226)Ra, (232)Th or (40)K.

PMID- 20680407
TI  - Physical activity, morbidity and mortality in twins: a 24-year prospective follow
      up.
AB  - The aim of this study was to find out whether persistent leisure-time physical
      activity, adjusted for genetic liability and childhood experiences, protect
      against occurrence of specific chronic diseases and all-cause mortality. Study
      design was a 24-year prospective follow-up after 6-year physical activity
      discordance in twin pairs. From 5,663 healthy adult twin pairs, 146 pairs
      (including 29 mozygotic) discordant for both intensity and volume of leisure
      physical activity at baseline in both 1975 and 1981 were systematically
      identified. Mortality and occurrence of chronic diseases (diabetes, hypertension,
      coronary heart disease defined according to reimbursable medication status) were
      followed for the period 1.1.1983-31.12.2006 for mortality and 1.1.1983-31.12.2004
      for diseases. By end of follow-up, 19 inactive and 10 active co-twins had died.
      In the whole sample, HR of death adjusted for social class was 2.08 (95% CI 1.06
      4.09) for inactive vs. active co-twins, the HR being 2.67 (95% CI 1.15-6.20)
      among DZ pairs with no mortality difference among the smaller number of
      discordant MZ pairs. The reimbursable medication analyses showed a tendency of
      higher risk for inactive vs. active co-twins. Among DZ pairs, HR of diabetes
      medication adjusted for social class was 2.73 (95% CI 0.62-12.00) and HR of
      hypertension medication was 2.14 (95% CI 0.94-4.89). This study supports the
      earlier findings that physical activity is associated with reduced mortality.
      However the difference was seen only in DZ pairs and therefore some residual
      genetic confounding effects on mortality cannot be excluded.

PMID- 20680408
TI  - Effects of ranolazine on fatty acid transformation in the isolated perfused rat
      liver.
AB  - It has been proposed that in the heart, ranolazine shifts the energy source from
      fatty acids to glucose oxidation by inhibiting fatty acid oxidation. Up to now no
      mechanism for this inhibition has been proposed. The purpose of this study was to
      investigate if ranolazine also affects hepatic fatty acid oxidation, with
      especial emphasis on cell membrane permeation based on the observations that the
      compound interacts with biological membranes. The isolated perfused rat liver was
      used, and [1-(14)C]oleate transport was measured by means of the multiple
      indicator dilution technique. Ranolazine inhibited net uptake of [1-(14)C]-oleate
      by impairing transport of this fatty acid. The compound also diminished the extra
      oxygen consumption and ketogenesis driven by oleate and the mitochondrial
      NADH/NAD(+) ratio, but stimulated (14)CO(2) production. These effects were
      already significant at 20 MUM ranolazine. Ranolazine also inhibited both oxygen
      consumption and ketogenesis driven by endogenous fatty acids in substrate-free
      perfused livers. In isolated mitochondria ranolazine inhibited acyl-CoA oxidation
      and beta-hydroxybutyrate or alpha-ketoglutarate oxidation coupled to ADP
      phosphorylation. It was concluded that ranolazine inhibits fatty acid uptake and
      oxidation in the liver by at least two mechanisms: inhibition of cell membrane
      permeation and by an inhibition of the mitochondrial electron transfer via
      pyridine nucleotides.

PMID- 20680409
TI  - Alterations in serum selenium levels and their relation to troponin I in acute
      myocardial infarction.
AB  - Selenium (Se) is an essential trace element with antioxidant function. The aim of
      the present study was to estimate the alterations of Se serum level during the
      acute phase of myocardial infarction and its relation to biomarkers of myocardial
      necrosis. Serum Se levels were measured at admission and after 24 h in 60
      consecutive patients with acute coronary syndrome (both with and without ST
      elevation). Troponin I (TnI) was assessed at admission and then twice daily for 3
      days; patients with normal levels were excluded. Fifty-five patients with acute
      MI (positive TnI) were included into the analysis. During the first day of
      hospitalization, patients received standard therapy, including acetylsalicylic
      acid, clopidogrel, and heparin or enoxaparin; all underwent urgent coronary
      angiography and percutaneous intervention, when appropriate. Mean Se levels at
      baseline and 24 h later were comparable (67.1 +/- 2.1 vs. 67.2 +/- 1.8 MUg/L,
      ns). Linear regression has shown significant correlation between baseline Se
      levels and peak TnI (y = 3.4x - 116, r (2) = 0.13, P = 0.008). Positive
      correlation was found also between the peak TnI and the difference from baseline
      to 24 h (y = 2.2x + 115, r (2) = 0.08, P = 0.04). Moreover, close negative
      correlation was observed between baseline Se levels and the difference from
      baseline to 24 h (y = -0.9x + 62.7, r (2) = 0.55, P<0.001). Our results have
      shown marked individual changes in Se levels during the acute phase of MI as well
      as correlation between Se levels and peak TnI. These results suggest that
      alterations in serum Se may be related to the extent of myocardial infarction.

PMID- 20680410
TI  - The role of neurofibromin in N-Ras mediated AP-1 regulation in malignant
      peripheral nerve sheath tumors.
AB  - Plexiform neurofibromas commonly found in patients with Neurofibromatosis type I
      (NF1) have a 5% risk of being transformed into malignant peripheral nerve sheath
      tumors (MPNST). Germline mutations in the NF1 gene coding for neurofibromin,
      which is a Ras GTPase activating protein (RasGAP) and a negative regulator of
      Ras, result in an upregulation of the Ras pathway. We established a direct
      connection between neurofibromin deficiency and downstream effectors of Ras in
      cell lines from MPNST patients by demonstrating that knockdown of NF1 expression
      using siRNA in a NF1 wild type MPNST cell line, STS-26T, activates the Ras/ERK1,2
      pathway and increases AP-1 binding and activity. We believe this is the first
      time the transactivation of AP-1 has been linked directly to neurofibromin
      deficiency in a disease relevant MPNST cell line. Previously, we have shown that
      N-Ras is constitutively activated in cell lines derived from independent MPNSTs
      from NF1 patients. We therefore sought to analyze the role of the N-Ras pathway
      in deregulating AP-1 transcriptional activity. We show that STS-26T clones
      conditionally expressing oncogenic N-Ras show increased phosphorylated ERK1,2 and
      phosphorylated JNK expression concomitant with increased AP-1 activity. MAP
      kinase pathways (ERK1,2 and JNK) were further examined in ST88-14, a
      neurofibromin-deficient MPNST cell line. The basal activity of ERK1,2 but not JNK
      was found to increase AP-1 activity. These experiments further confirmed the link
      between the loss of neurofibromin and increased activity of Ras/MAP kinase
      pathways and the activation of downstream transcriptional mechanisms in MPNSTs
      from NF1 patients.

PMID- 20680412
TI  - Studies of early growth mechanisms of hydroxyapatite on single crystalline
      rutile: a model system for bioactive surfaces.
AB  - Previous studies have shown that crystalline titanium oxide is in vitro bioactive
      and that there are differences in the HA formation mechanism depending on the
      crystalline direction of the titanium oxide surface. In the present study, the
      early adsorption of calcium and phosphate ions on three different surface
      directions of the single-crystal rutile TiO(2) substrate has been investigated. A
      crucial step in the nucleation of HA is believed to be the adsorption of Ca(2+)
      and PO(4)(3-) from phosphate buffer solutions. The (001), (100) and (110) single
      crystalline rutile surfaces were soaked in phosphate buffer saline solution for
      10 min, 1 h and 24 h at 37 degrees C. The surfaces were then analyzed using time
      of-flight secondary ion mass spectrometry (TOF-SIMS) and X-ray photoelectron
      spectroscopy (XPS). The results show that the adsorption of Ca(2+) and PO(4)(3-)
      is faster on the (001) and (100) surfaces than on the (110) surface. This study
      also shows that TOF-SIMS can be used as a tool to better understand the
      adsorption of calcium and phosphate ions and the growth mechanism of HA. This
      knowledge could be used to tailor new bioactive surfaces for better biological
      reaction.

PMID- 20680411
TI  - Molecular susceptibility to glycation and its implication in diabetes mellitus
      and related diseases.
AB  - The modification of free amino groups on proteins, lipids, and nucleic acids by
      non-enzymatic glycosylation produce a variety of complex structures named
      advanced glycation end products (AGEs). Glycation of these molecules participate
      in the development of diabetic complications and related diseases. Diabetes
      mellitus is characterized by short-term metabolic changes in lipid and protein
      metabolism, and long-term irreversible changes in vascular and connective tissue.
      AGEs are directly implicated in the development of chronic complications in
      diabetes such as nephropathy, rethinopathy, neuropathy, and other related
      diseases such as atherosclerosis, heart disease, stroke, and peripheral vascular
      disease. In this review, we aim to explain how glycation occurs in different
      molecules and what the pathological consequence of AGE formation in diabetes
      mellitus and other diseases are.

PMID- 20680413
TI  - Effect of pyrophosphate ions on the conversion of calcium-lithium-borate glass to
      hydroxyapatite in aqueous phosphate solution.
AB  - The conversion of glass to a hydroxyapatite (HA) material in an aqueous phosphate
      solution is used as an indication of the bioactive potential of the glass, as
      well as a low temperature route for preparing biologically useful materials. In
      this work, the effect of varying concentrations of pyrophosphate ions in the
      phosphate solution on the conversion of a calcium-lithium-borate glass to HA was
      investigated. Particles of the glass (150-355 MUm) were immersed for up to 28
      days in 0.25 M K(2)HPO(4) solution containing 0-0.1 M K(4)P(2)O(7). The kinetics
      of degradation of the glass particles and their conversion to HA were monitored
      by measuring the weight loss of the particles and the ionic concentration of the
      solution. The structure and composition of the conversion products were analyzed
      using X-ray diffraction, scanning electron microscopy, and Fourier transform
      infrared spectroscopy. For K(4)P(2)O(7) concentrations of up to 0.01 M, the glass
      particles converted to HA, but the time for complete conversion increased from 2
      days (no K(4)P(2)O(7)) to 10 days (0.01 M K(4)P(2)O(7)). When the K(4)P(2)O(7)
      concentration was increased to 0.1 M, the product consisted of an amorphous
      calcium phosphate material, which eventually crystallized to a pyrophosphate
      product (predominantly K(2)CaP(2)O(7) and Ca(2)P(2)O(7)). The consequences of the
      results for the formation of HA materials and devices by the glass conversion
      route are discussed.

PMID- 20680414
TI  - Attractants for rice leaf bug, Trigonotylus caelestialium (Kirkaldy), are emitted
      from flowering rice panicles.
AB  - Volatiles were extracted from rice plants of various growth stages with solid
      phase microextraction (SPME) and analyzed by gas chromatography-mass spectrometry
      (GC-MS) to identify attractants that cause invasion of the rice leaf bug
      Trigonotylus caelestialium (Kirkaldy) into paddy fields. The composition of
      volatile blends produced by rice plants changed with rice development. In
      addition, volatile blend compositions differed between the panicles and the stems
      and leaves. The relative geranyl acetone content was high in all plant structures
      analyzed. In volatiles from whole plants in the fourth-leaf stage and panicles in
      the full-ripe stage, the relative content of green leaf volatiles (GLVs) was
      higher than that found in other rice plant structures. In contrast, relative
      terpene levels emitted from whole plants in the panicle-formation stage and by
      panicles and stems and leaves in the flowering stage were higher than those of
      other rice plant structures. However, the type of terpenes found differed between
      the panicles and the stems and leaves. Relative levels of beta-caryophyllene in
      whole plants in the panicle-formation stage and panicles in the flowering stage
      were much higher than that in stems and leaves in the flowering stage. Our
      previous studies demonstrated that the odor from whole plants in the panicle
      formation stage and panicles in the flowering stage is attractive to rice leaf
      bugs. Here, the attractiveness of beta-caryophyllene to adult bugs was
      investigated in olfactometer assays. Adult females were attracted to beta
      caryophyllene at a concentration of 0.001%, which is approximately equivalent to
      the concentration produced by flowering rice panicles. However, beta
      caryophyllene also was present in the odor of whole plants in the fourth-leaf
      stage and in stems and leaves in the flowering stage. Furthermore, the amounts of
      this compound emitted from these structures were similar. Therefore, we suggest
      that the relative abundance of this compound in a volatile blend is important for
      attractance of the bugs.

PMID- 20680415
TI  - Field response of male pine sawflies, Neodiprion sertifer (Diprionidae), to sex
      pheromone analogs in Japan and Sweden.
AB  - The pine sawfly Neodiprion sertifer (Geoffroy) uses the acetate or propionate of
      (2S,3S,7S)-3,7-dimethyl-2-pentadecanol (diprionol) as pheromone components, with
      the (2S,3R,7R)-isomer being antagonistic, synergistic, or inactive according to
      the population tested. In this study, we tested the attraction of males to the
      acetates of three analogs of diprionol, each missing one methyl group, viz.
      (2S,7S)-7-methyl-2-pentadecanol, (2S,6S)-2,6-dimethyl-1-tetradecanol, and (2S,3S)
      3-methyl-2-pentadecanol. None of the analogs alone, or in combination with
      diprionol acetate, was attractive in Sweden, even at 100 times the amount of
      diprionol acetate attractive to N. sertifer. In Japan, the acetate of (2S,3S)-3
      methyl-2-pentadecanol attracted males when tested in amounts 10-20 times higher
      than the acetate pheromone component. The acetate esters of the (2S,3R)-analog
      and the (2S,3R,7R)-isomer of diprionol also were tested in combination with the
      pheromone compound (acetate ester). Both compounds caused an almost total trap
      catch reduction in Sweden, whereas in Japan they appear to have relatively little
      effect on trap capture when added to diprionol acetate. Butyrate and iso-butyrate
      esters of diprionol were unattractive to N. sertifer in Sweden. In summary, there
      exists geographic variation in N. sertifer in responses to both diprionyl acetate
      and some of its analogs.

PMID- 20680416
TI  - Isolation of mammary-specific extracellular matrix to assess acute cell-ECM
      interactions in 3D culture.
AB  - Studies of mammary epithelial cells (MECs) cultured with reconstituted basement
      membrane proteins derived from EHS tumors have contributed greatly to the
      understanding of both normal physiology and transformation. Only when plated on
      such biologically relevant substratum are MECs able to form morphologically
      correct, differentiated structures, highlighting a critical role for
      extracellular matrix (ECM) proteins in MEC organization and function. Here, we
      describe methods modified from the original EHS matrix protocol for isolating
      tissue-specific ECM from rat mammary glands, and for subsequent use in short-term
      3D cell culture models designed to assess acute cell-ECM interactions. Using this
      protocol, the final matrix is enriched up to 58-fold for ECM proteins such as
      fibronectin and laminin, while cellular proteins such as GAPDH are reduced 98
      fold. We have previously shown that MECs plated in mammary-specific ECM form more
      elaborate duct-like and alveolar-like structures compared to MECs plated in
      MatrigelTM, demonstrating the biological relevance of tissue-specific ECM. Use of
      mammary-specific ECM in 3D cell culture models will further our ability to study
      the intricate interplay between a cell and its microenvironment, and permit
      identification of modifying factors.

PMID- 20680417
TI  - Gambling motivation and passion: a comparison study of recreational and
      pathological gamblers.
AB  - The aim of this study was to examine the structural relationship among gambling
      motivation, gambling passion, and behavioral intentions to gamble between
      recreational and pathological gamblers. Specifically, this study aimed to shed
      light on the different ways in which gambling motivation and affective attitude
      are associated with recreational and pathological gamblers. Using a purposive
      sampling method, 400 subjects were selected for and participated in this study
      during their visits to a casino. Study results echoed the notion of distinctive
      and separate gambling motivations and passions between recreational and
      pathological gamblers. Also, results identified specific areas to which casino
      operators or policy makers should pay special attention in developing effective
      marketing strategies to promote responsible gambling.

PMID- 20680418
TI  - Impediments to DNA testing and cascade screening for hypertrophic cardiomyopathy
      and Long QT syndrome: a qualitative study of patient experiences.
AB  - This paper reports data from a qualitative study of patient experiences of DNA
      testing and cascade screening for hypertrophic cardiomyopathy and long QT
      syndrome, cardiac conditions that place sufferers at risk of sudden death. The
      paper particularly focuses on potential impediments to testing and screening.
      Semi-structured interviews were undertaken with a purposive sample of 27 people
      in the UK who had undergone testing. In the context of the uncertainties that can
      characterize experiences of these disorders, the majority of participants in this
      sample embraced testing and screening as a way of providing health information
      for themselves or their relatives (particularly children). There was nevertheless
      evidence of ambivalence about the value and impact of the DNA test information
      which could influence participants' dispositions toward testing, and play into
      dilemmas about family communication. Other concerns arose in relation to
      communicating about these disorders, decisions to involve elderly relatives and
      pressures relating to family responsibility. The evidence of ambivalence provides
      insight into why some people may be resistant to testing, screening and sharing
      information. The findings about communication processes indicate potential areas
      of concern for the cascading process.

PMID- 20680419
TI  - Death anxiety and symbolic immortality in relatives at risk for familial amyloid
      polyneuropathy type I (FAP I, ATTR V30M).
AB  - This study is an investigation of the impact of familial amyloid polyneuropathy
      type I (FAP I, ATTR V30M) on death anxiety and symbolic immortality. Templer and
      Drolet's scales were administered to 524 individuals: (1) 84 relatives at risk,
      (2) 92 relatives not at risk for FAP I; and (3) a control group (n = 348) with no
      known hereditary disease in their families. At-risk relatives had, on average, a
      higher score for death anxiety and a lower score for symbolic immortality, than
      either those not-at-risk or controls. There were no significant differences in
      scores on either measure for those not-at-risk versus controls. Being at risk
      increases death anxiety and threatens the sense of symbolic immortality and
      psychosocial wellbeing. This may be true for other serious hereditary disorders
      as well. Genetic counsellors should become familiar with these concepts, feel
      comfortable initiating discussions about death with their patients, and be able
      to identify and reinforce their patients' and family members' sense of symbolic
      immortality.

PMID- 20680420
TI  - "What would you do if you were me?" Effects of counselor self-disclosure versus
      non-disclosure in a hypothetical genetic counseling session.
AB  - Two prior studies suggest genetic counselors self-disclose primarily because
      patients ask them to do so (Peters et al., 2004; Thomas et al., 2006). However,
      scant research has investigated effects of counselor disclosure on genetic
      counseling processes and outcomes. In this study, 151 students (98
      undergraduates, 53 graduates) completed one of three surveys describing a
      hypothetical genetic counseling session in which a patient at risk for FAP was
      considering whether to pursue testing or surveillance procedures. Dialogue was
      identical in all surveys, except for a final response to the question: "What
      would you do if you were me?" The counselor either revealed what she would do
      (Personal Disclosure), what other patients have done (Professional Disclosure),
      or deflected the question (No Disclosure). Imagining themselves as the patient,
      participants wrote a response to the counselor and indicated their perceptions of
      her. Participants rated the non-disclosing counselor significantly lower in
      social attractiveness than either disclosing counselor, and less satisfying than
      the professional disclosing counselor. Analysis of written responses yielded four
      themes: Made Decision, Sought Information, Expressed Thoughts/Feelings, and No
      Decision. Practice implications and research recommendations are provided.

PMID- 20680422
TI  - Exploring hereditary cancer among dying cancer patients--a cross-sectional study
      of hereditary risk and perceived awareness of DNA testing and banking.
AB  - Hereditary cancer assessment at the end of life is a relatively unexplored area,
      but it could be critical for surviving family members. This study explored the
      prevalence of hereditary cancer among dying cancer patients and assessed
      patients' perceived awareness of DNA testing and/or banking in a public access
      hospital. Palliative care patients with cancer from a single institution (or
      their medical-decision-making surrogates for patients unable to answer for
      themselves) completed structured interviews. Information was collected through
      medical records review and structured interviews for 43 dying cancer patients.
      Information for 9 patients was collected from surrogates. Nine patients (21%, 95%
      CI = 8.8% to 33.1%) had strong genetic risk. Currently available genetic tests
      could have addressed this risk for several patients. None had previous genetic
      counseling, testing or DNA banking. Among strong-risk patients, about half of
      patients/surrogates had heard/read "almost nothing" about genetic testing (44%)
      and DNA banking (67%). Perceived genetic awareness was not associated with
      genetic risk, and neither were sociodemographic characteristics. The proportion
      of hereditary cancer may be at least as high in the palliative care population as
      in other clinical settings, but awareness and uptake among patients are low.
      These conditions are not being recognized upstream and families are losing
      valuable information.

PMID- 20680421
TI  - Socioeconomic status and psychological function in children with chromosome
      22q11.2 deletion syndrome: implications for genetic counseling.
AB  - The purpose of this study is to examine the association between parental socio
      economic status (SES) and childhood neurocognition and behavior in children with
      chromosome 22q11.2 deletion syndrome (22q11DS). Although undoubtedly, the
      deletion of genes in the 22q11.2 interval is primarily responsible for the
      psychological manifestations, little is known about the role of the environment
      in either mitigating or contributing to these problems. We examined the
      association of parental socio-economic status (SES) with cognition and behavior
      in children with 22q11DS (n = 65) and matched healthy control subjects (n = 52),
      since SES is a component of family resources. We found that in children with
      22q11DS, higher SES correlated with better overall functioning (p < .01) and
      social skills (p < .01), and less frequent oppositional defiant behavior (p <
      .001). These findings were in contrast to the control subjects in whom SES
      correlated with cognition and achievement, but not behavior. Our results indicate
      that environmental factors influence the behavioral phenotype in children with
      22q11DS, providing a framework for developing appropriate interventions. As such,
      genetic counseling for families with 22q11DS may include consideration of family
      resources and inclusion of other health professionals, such as social workers, to
      explore with the family available social supports and resources.

PMID- 20680423
TI  - Biobanks: importance, implications and opportunities for genetic counselors.
AB  - Biobanks are collections of human biological tissue specimens and related health
      data. Biobank research hopes to provide novel insights into the genetic component
      of disease, ultimately leading to a more personalized approach to healthcare.
      However, biobanks have sparked debate due to the ethical, legal, and social
      implications surrounding utilization of population samples and data. These
      controversies include issues of consent, privacy and confidentiality, return of
      results and data-sharing. This paper provides an overview of the different types
      and scope of biobanks and an examination of the most pertinent ethical, legal and
      social considerations surrounding such research, as well as how some of these
      concerns are being addressed. The paper finishes with a discussion of the
      relevance of biobanks to the genetic counseling field and concludes that genetic
      counselors are in a position to make a unique, educated and practical
      contribution to the ongoing dialogue and direction of biobank research.

PMID- 20680424
TI  - Adolescent thriving: the role of sparks, relationships, and empowerment.
AB  - Although most social science research on adolescence emphasizes risks and
      challenges, an emergent field of study focuses on adolescent thriving. The
      current study extends this line of inquiry by examining the additive power of
      identifying and nurturing young people's "sparks," giving them "voice," and
      providing the relationships and opportunities that reinforce and nourish
      thriving. A national sample of 1,817 adolescents, all age 15 (49% female), and
      including 56% white, 17% Hispanic/Latino, and 17% African-American adolescents,
      completed an online survey that investigated their deep passions or interests
      (their "sparks"), the opportunities and relationships they have to support
      pursuing those sparks, and how empowered they feel to make civic contributions
      (their "voice"). Results consistently supported the hypothesis that linking one's
      spark with a sense of voice and supportive opportunities and relationships
      strengthens concurrent outcomes, particularly those reflecting prosociality,
      during a key developmental transition period. The three developmental strengths
      also predicted most outcomes to a greater degree than did demographics. However,
      less than 10 percent of 15-year-olds reported experiencing high levels of all
      three strengths. The results demonstrate the value of focusing on thriving in
      adolescence, both to reframe our understanding of this age group and to highlight
      the urgency of providing adolescents the opportunities and relationships they
      need to thrive.

PMID- 20680425
TI  - Traditional and cyber aggressors and victims: a comparison of psychosocial
      characteristics.
AB  - To date, relatively little is known about differences between perpetrators and
      victims of cyber and traditional forms of aggression. Hence, this study
      investigated differences among traditional and cyber aggressors and victims on
      psychosocial characteristics typically examined in research on traditional
      aggression and victimization, specifically effortful control, manipulativeness,
      remorselessness, proactive and reactive aggression, and anxious/depressive
      symptoms. Participants (N = 300; 63.2% female; M age = 12.89, SD = .95; 52%
      Caucasian, 27% African American, 11% Latino, and 10% other) were categorized
      based on aggressor type (non/low aggressor, traditional-only, cyber-only, and
      combined traditional and cyber) and victim type (non-victim, traditional-only,
      cyber-only, and combined traditional and cyber). Cyber aggressors reported lower
      levels of reactive aggression compared to traditional-only and combined
      aggressors. Combined aggressors demonstrated the poorest psychosocial profile
      compared to all other aggressor groups. For victimization, cyber-only and
      combined victims reported higher levels of reactive aggression and were more
      likely to be cyber aggressors themselves compared to traditional-only victims and
      non-victims. Findings suggest that there may be unique aspects about cyber
      aggression and victimization that warrant further investigation.

PMID- 20680426
TI  - Beneficial effects of physical training on the cardio-inflammatory disorder
      induced by lung ischemia/reperfusion in rats.
AB  - Our laboratory demonstrated that training program attenuated the inflammatory
      responses in lung ischemia/reperfusion (IR). Considering the importance of the
      inflammatory responses on the cardiovascular system, we evaluate the effect of
      physical training on the vascular responsiveness and its underlying mechanism
      after lung IR. Male Wistar rats were submitted to run training and lung IR.
      Concentration-response curves for relaxing and contracting agents were obtained.
      Protein expressions of SOD-1 and p47(phox), plasma nitritre/nitrate (NO (x) (-) )
      and interleukin 6 (IL-6) were evaluated. A decreased in the potency for
      acetylcholine and phenylephrine associated with an upregulation of the p47(phox)
      expression were found after Lung IR as well as an increase in IL-6 and NO (x) (-)
      levels. Run training attenuated the vascular dysfunction that was accompanied by
      reduction of the p47(phox) protein expression and IL-6 levels. Our findings show
      the beneficial effect of training on the vascular function that was associated
      with reduction in inflammatory response in lung IR.

PMID- 20680427
TI  - Controlled evaluation of the effects of hyperbaric oxygen therapy on the behavior
      of 16 children with autism spectrum disorders.
AB  - Hyperbaric oxygen therapy (HBOT) has been used to treat individuals with autism.
      However, few studies of its effectiveness have been completed. The current study
      examined the effects of 40 HBOT sessions at 24% oxygen at 1.3 ATA on 11
      topographies of directly observed behavior. Five replications of multiple
      baselines were completed across a total of 16 participants with autism spectrum
      disorders. No consistent effects were observed across any group or within any
      individual participant, demonstrating that HBOT was not an effective treatment
      for the participants in this study. This study represents the first relatively
      large-scale controlled study evaluating the effects of HBOT at the level of the
      individual participant, on a wide array of behaviors.

PMID- 20680428
TI  - Radioprotective effect of geraniin via the inhibition of apoptosis triggered by
      gamma-radiation-induced oxidative stress.
AB  - The radioprotective effect of geraniin, a tannin compound isolated from Nymphaea
      tetragona Georgi var. (Nymphaeaceae), against gamma-radiation-induced damage was
      investigated in Chinese hamster lung fibroblast (V79-4) cells. Geraniin recovered
      cell viability detected by MTT test and colony formation assay, which was
      compromised by gamma-radiation, and reduced the gamma-radiation-induced apoptosis
      by the inhibition of loss of the mitochondrial membrane potential. Geraniin
      protected cellular components (lipid membrane, cellular protein, and DNA) damaged
      by gamma-radiation, which was detected by lipid peroxidation, protein carbonyl
      formation, and comet assay. Geraniin significantly reduced the level of
      intracellular reactive oxygen species generated by gamma-radiation, which was
      detected using spectrofluorometer, flow cytometer, and confocal microscope after
      2',7'-dichlorodihydrofluorescein diacetate staining. Geraniin normalized the
      superoxide dismutase and catalase activities, which were decreased by gamma
      radiation. These results suggest that geraniin protects cells against radiation
      induced oxidative stress via enhancing of antioxidant enzyme activities and
      attenuating of cellular damage.

PMID- 20680429
TI  - Sodium fluoride influences the expression of keratins in cultured keratinocytes.
AB  - Epithelia in lung, skin, and kidney are often exposed to fluoride, and tissue
      damage in lung and kidney due to fluoride is well documented. Nevertheless, the
      biological effects of fluoride on epithelia are poorly investigated. In the
      present study, we report effects of sodium fluoride (NaF) on the differentiation
      of a human epithelial cell line, HaCaT. These cells may serve as a keratinocyte
      model, because they express a wide spectrum of keratins (Ks), and they associate
      into stratified tissue-like arrangements along with changes in their keratin
      pattern. NaF was added to the culture medium at concentrations of 0.5 and 5 mM.
      Cell proliferation remained intact, but cell functions were altered at high dose,
      and HSP70 was induced. Reverse transcription-polymerase chain reaction and
      Western blotting revealed that keratin (K) 15 mRNA and protein expression,
      associated with stratification of epithelia, were inhibited. Also, expression of
      keratins typical for terminal differentiation, K1 and K10, was decreased and so
      was the expression of the K1/10 regulating enhancer binding protein c/EBP alpha.
      Stratification of HaCaT cells was abolished at high fluoride dose, as assessed by
      electron microscopy. The changes in keratin expression were not reversed by
      withdrawal of fluoride. Taken together, NaF at high dose blocked terminal
      differentiation of HaCaT cells, visible by keratin expression and failing
      stratification. This effect may disturb tissue formation due to altered cell
      interactions.

PMID- 20680430
TI  - No associations between single nucleotide polymorphisms in corticoid receptor
      genes and heart rate and cortisol responses to a standardized social stress test
      in adolescents: the TRAILS study.
AB  - Previously, sequence variation in the glucocorticoid (GR) and mineralocorticoid
      (MR) receptor genes (NR3C1 and NR3C2, respectively) have been found to be
      associated with physiological stress responses to social stress tests in small
      samples of adult men and oral contraceptives (OC) using women. Associations
      between single nucleotide polymorphisms (SNPs) in the GR (23EK-rs6190, 9beta
      rs6198, BclI-rs4142324) and the MR gene (I180V-rs5522 and -2G/C (rs2070951) with
      cortisol and heart rate responses to a performance-related social stress task
      (public speaking and mental arithmetic) were examined in a large sample (n = 553)
      of adolescents (15-17 years). To make comparisons with previous findings,
      associations were tested in boys (n = 277), free-cycling (FC) girls (n = 183) and
      OC users (n = 93). None of the previously reported associations in adults could
      be replicated in this large adolescent sample. Explanations for non-replication
      are discussed.

PMID- 20680431
TI  - Internalizing behavior in adolescent girls affects parental emotional
      overinvolvement: a cross-lagged twin study.
AB  - The aim of this study was to examine the direction and the etiology of the
      association between different parenting styles (parental emotional
      overinvolvement [EOI] and parental criticism) and internalizing behavior from
      adolescence to early adulthood. A longitudinal genetically informative cross
      lagged design was applied to a population-based sample of Swedish twins contacted
      at age 16-17 (n = 2369) and at age 19-20 (n = 1705). Sex-limitation modelling
      revealed different effects for boys and girls. For girls, genetic influences on
      internalizing problems at age 16-17 independently explained 2.7% of the
      heritability in parental EOI at age 19-20. These results suggest that emotionally
      overinvolved and self-sacrificing parental behavior stems in part from daughters
      (but not sons) genetic predisposition for internalizing behavior. These findings
      highlight the importance of genetically influenced child-driven effects
      underlying the parenting-internalizing association, and clarify that the role of
      such effects may differ depending on sex, type of parenting and developmental
      period.

PMID- 20680432
TI  - Efficacy of personalized cognitive counseling in men of color who have sex with
      men: secondary data analysis from a controlled intervention trial.
AB  - In a previous report, we demonstrated the efficacy of a cognitively based
      counseling intervention compared to standard counseling at reducing episodes of
      unprotected anal intercourse (UAI) among men who have sex with men (MSM) seeking
      HIV testing. Given the limited number of efficacious prevention interventions for
      MSM of color (MOC) available, we analyzed the data stratified into MOC and
      whites. The sample included 196 white MSM and 109 MOC (23 African Americans, 36
      Latinos, 22 Asians, eight Alaskan Natives/Native Americans/Hawaiian/Pacific
      Islander, and 20 of mixed or other unspecified race). Among MOC in the
      intervention group, the mean number of episodes of UAI declined from 5.1 to 1.6
      at six months and was stable at 12 months (1.8). Among the MOC receiving standard
      counseling, the mean number of UAI episodes was 4.2 at baseline, 3.9 at six
      months and 2.1 at 12 months. There was a significant treatment effect overall
      (relative risk 0.59, 95% confidence interval 0.35-0.998). These results suggest
      that the intervention is effective in MOC.

PMID- 20680433
TI  - Young adulthood body mass index and risk of cancer in later adulthood: historical
      cohort study.
AB  - OBJECTIVE: To investigate the relationship between body mass index (BMI) in young
      adulthood and cancer incidence and mortality. METHODS: A total of 9,549 men and
      2,657 women had weight and height measured while at university (1948-1968).
      Participants were traced through the National Health Service Central Register,
      and cancer registration and death certificates were obtained. Cox proportional
      hazard models were used to estimate hazard ratios (HR) of associations between
      BMI and cancer incidence and mortality. RESULTS: The mean age at university was
      20 years. During a median follow-up of 49 years, 2,349 deaths occurred, including
      55 breast, 111 prostate, and 131 colorectal cancer. There were 1,305 cancer
      registrations, including 102 breast, 211 prostate, and 125 colorectal cancers.
      There was weak evidence of an association between BMI and colorectal cancer
      incidence (adjusted HR per 1 kg/m(2): 1.06, 95% CI: 0.98-1.15) and mortality (HR
      1.05, 95% CI: 0.98-1.14). There was no evidence of an association between BMI and
      either breast or prostate cancer. CONCLUSIONS: Targeting a reduction in obesity
      in young adulthood may prevent a significant number of colorectal cancer deaths,
      although whether this relationship is direct or through tracking to later adult
      BMI has yet to be established.

PMID- 20680434
TI  - Nighttime light level co-distributes with breast cancer incidence worldwide.
AB  - Breast cancer incidence varies widely among countries of the world for largely
      unknown reasons. We investigated whether country-level light at night (LAN) is
      associated with incidence. We compared incidence rates of five common cancers in
      women (breast, lung, colorectal, larynx, and liver), observed in 164 countries of
      the world from the GLOBOCAN database, with population-weighted country-level LAN,
      and with several developmental and environmental indicators, including fertility
      rate, per capita income, percent of urban population, and electricity
      consumption. Two types of regression models were used in the analysis: Ordinary
      Least Squares and Spatial Errors. We found a significant positive association
      between population LAN level and incidence rates of breast cancer. There was no
      such an association between LAN level and colorectal, larynx, liver, and lung
      cancers. A sensitivity test, holding other variables at their average values,
      yielded a 30-50% higher risk of breast cancer in the highest LAN exposed
      countries compared to the lowest LAN exposed countries. The possibility that
      under-reporting from the registries in the low-resource, and also low-LAN,
      countries created a spurious association was evaluated in several ways and shown
      not to account for the results. These findings provide coherence of the
      previously reported case-control and cohort studies with the co-distribution of
      LAN and breast cancer in entire populations.

PMID- 20680435
TI  - Coffee consumption and risk of colorectal cancer: a meta-analysis of case-control
      studies.
AB  - A meta-analysis of case-control studies on coffee consumption and colorectal
      cancer risk was conducted. Twenty-four eligible studies published before May 2010
      were identified, including a total of 14,846 cases of colorectal, colon or rectal
      cancer. Compared to non/occasional drinkers, the odds ratios (OR) for drinkers
      were 0.83 (95% CI 0.73-0.95) for colorectal, 0.93 (95% CI 0.81-1.07) for colon
      and 0.98 (95% CI 0.85-1.13) for rectal cancer, with significant heterogeneity
      among studies; the corresponding ORs for the increment of 1 cup/day were 0.94
      (95% CI 0.91-0.98), 0.95 (95% CI 0.92-0.98), and 0.97 (95% CI 0.95-0.99). For the
      highest coffee drinkers, the ORs were 0.70 (95% CI 0.60-0.81) for colorectal
      cancer, 0.75 (95% CI 0.64-0.88) for colon cancer and 0.87 (95% CI 0.75-1.00) for
      rectal cancer, when compared to non/low drinkers. The results of this meta
      analysis of case-control studies suggest a moderate favorable effect of coffee
      consumption on colorectal cancer risk. The reduced risk was consistent across
      study design (hospital vs. population based), geographic area, and various
      confounding factors considered. It may reflect a real protection but also partly
      or largely be due to reverse causation, i.e. decreased coffee consumption among
      cases following the onset of bowel symptoms.

PMID- 20680436
TI  - Tea and coffee intake in relation to risk of breast cancer in the Black Women's
      Health Study.
AB  - OBJECTIVE: Prospective studies of tea and coffee intake and breast cancer risk
      have yielded inconsistent results. None of these studies has reported separately
      on African-American women. We prospectively examined the relation of tea and
      coffee consumption to risk of breast cancer among 52,062 women aged 21-69 at
      enrollment in 1995 in the Black Women's Health Study. METHODS: Dietary intake was
      assessed in 1995 and 2001 using a validated food frequency questionnaire. Cox
      proportional hazards models were used to estimate incidence rate ratios (IRR) and
      95% confidence intervals (CI), adjusted for breast cancer risk factors. RESULTS:
      During 12 years of follow-up through 2007, there were 1,268 incident cases of
      breast cancer. Intakes of tea, coffee, and caffeine were not significantly
      associated with the risk of breast cancer overall. The IRRs for consumption of
      >=4 cups/day compared with none were 1.13 (95% CI 0.78-1.63) for tea and 1.03
      (95% CI 0.77-1.39) for caffeinated coffee, and the IRR for the top quintile
      relative to the bottom quintile of caffeine intake was 1.04 (95% CI 0.87-1.24).
      Consumption of tea, coffee, and caffeine was not significantly associated with
      breast cancer risk according to menopausal status or hormone receptor status.
      CONCLUSION: Our findings suggest that intakes of tea, coffee, and caffeine are
      not associated with the risk of breast cancer among African-American women.

PMID- 20680437
TI  - Nutrient dietary patterns and the risk of colorectal cancer: a case-control study
      from Italy.
AB  - OBJECTIVE: The role of diet on colorectal cancer has been considered in terms of
      single foods and nutrients, but less frequently in terms of dietary patterns.
      METHODS: Data were derived from an Italian case-control study, including 1,225
      subjects with cancer of the colon, 728 subjects with rectal cancer, and 4,154
      hospital controls. We identified dietary patterns on a selected set of nutrients
      through principal component factor analysis. Odds ratios (OR) and 95% confidence
      intervals for both cancers were estimated using unconditional multiple logistic
      regression. RESULTS: We identified 5 major dietary patterns. Direct associations
      were observed between the Starch-rich pattern and both cancer of the colon (OR =
      1.68) and of the rectum (OR = 1.74). Inverse relationships were found between the
      Vitamins and fiber pattern and rectal cancer (OR = 0.61), between the Unsaturated
      fats (animal source) and the Unsaturated fats (vegetable source) and cancer of
      the colon (OR = 0.80 and OR = 0.79, respectively). No other significant
      association was found. CONCLUSIONS: The Starch-rich pattern is potentially an
      unfavorable indicator of risk for both colon and rectal cancer, whereas the
      Vitamins and fiber pattern is associated with a reduced risk of rectal cancer and
      the Unsaturated fats patterns with a reduced risk of colon cancer.

PMID- 20680438
TI  - Partnering with children diagnosed with mental health issues: contributions of a
      sociology of childhood perspective to participatory action research.
AB  - This paper explores the use of participatory action research (PAR) with children
      diagnosed with mental health issues. We argue that critiques from the sociology
      of childhood are useful for guiding PAR with children. First, we describe and
      critique values and assumptions that underlie research and practice with children
      who experience mental health issues. Second, we outline key qualities of the
      sociology of childhood, discuss their implications for PAR with children
      diagnosed with mental health issues, and touch on ethical issues. Five themes are
      explored: (a) values, (b) ontology/epistemology, (c) views about children, (d)
      agency/power in children's relationships with adults, and (e) intervention/change
      focus. We conclude by encouraging community psychologists to consider PAR with
      children diagnosed with mental health issues.

PMID- 20680439
TI  - Heart rate variability (HRV) and posttraumatic stress disorder (PTSD): a pilot
      study.
AB  - Exposure to combat experiences is associated with increased risk of developing
      Post Traumatic Stress Disorder. Prolonged exposure therapy and cognitive
      processing therapy have garnered a significant amount of empirical support for
      PTSD treatment; however, they are not universally effective with some patients
      continuing to struggle with residual PTSD symptoms. Heart rate variability (HRV)
      is a measure of the autonomic nervous system functioning and reflects an
      individual's ability to adaptively cope with stress. A pilot study was undertaken
      to determine if veterans with PTSD (as measured by the Clinician-Administered
      PTSD Scale and the PTSD Checklist) would show significantly different HRV prior
      to an intervention at baseline compared to controls; specifically, to determine
      whether the HRV among veterans with PTSD is more depressed than that among
      veterans without PTSD. The study also aimed at assessing the feasibility,
      acceptability, and potential efficacy of providing HRV biofeedback as a treatment
      for PTSD. The findings suggest that implementing an HRV biofeedback as a
      treatment for PTSD is effective, feasible, and acceptable for veterans. Veterans
      with combat-related PTSD displayed significantly depressed HRV as compared to
      subjects without PTSD. When the veterans with PTSD were randomly assigned to
      receive either HRV biofeedback plus treatment as usual (TAU) or just TAU, the
      results indicated that HRV biofeedback significantly increased the HRV while
      reducing symptoms of PTSD. However, the TAU had no significant effect on either
      HRV or symptom reduction. A larger randomized control trial to validate these
      findings appears warranted.

PMID- 20680440
TI  - Determination of organochlorine pesticides in the agricultural soil of Oke-Osun
      farm settlement, Osogbo, Nigeria.
AB  - This study was conducted to evaluate the levels and seasonal variations of some
      organochlorine pesticides (OCPs) in the cultivated land of Oke-Osun farm
      settlement, Osogbo, Nigeria. A field sampling programme was conducted in the
      rainy and dry seasons for 4 months each resulting in the analysis of a total of
      40 samples. Soil samples collected at 20-m intervals were air-dried to a constant
      weight, sieved through a mesh of 2.0-mm pore size and selected by coning and
      quartering method. Solid-liquid extraction was used to extract OCPs from the
      soil. Qualitative identifications and quantitative evaluation of the OCPs were
      carried out with the aid of a Perkin Elmer gas chromatograph coupled with
      electron capture detector. Seasonal mean ranges of OCPs in soil (MUg/kg) were
      13.09 +/- 21.66 beta-BHC-42.01 +/- 17.50 p, p(')-DDT in rainy season and 30.74 +/
      17.38 alpha-BHC-82.88 +/- 32.24 p, p(')-DDT in the dry season. The results
      obtained from this study revealed that agricultural soil samples of Oke-Osun farm
      settlement were contaminated with persistent organochlorine pesticides mainly as
      a result of their applications by farmers. Higher levels of OCPs were obtained
      for dry season than the rainy season. There were indications from this study that
      pesticides that have deleterious health effects on humans previously placed under
      legal restrictions by regulatory agencies were still being used by the farmers of
      Oke-Osun farm settlement and this gives cause for environmental concern.

PMID- 20680441
TI  - An HPLC method development for the assessment of degradation products of
      anthraquinone dye.
AB  - This paper describes the development of a simple and sensitive method with
      reduced run time for the estimation of biodegradation product of an anthraquinone
      dye, Drimarene blue K(2)RL. The chromatographic analysis was performed using a
      reversed-phase high performance liquid chromatography (HPLC) with a
      Lichrospher(r) RP-18 column, 5 MUm particle size, 25 cm * 4.6 mm internal
      diameter using a 70:20:10 (v/v) mixture of acetonitrile-ammonium acetate buffer
      (0.02 M) with 0.8% Trifluoroacetic acid (pH 2.5) and methanol as eluent. Flow
      rate was adjusted to 1.2 mL min(-1). The metabolites (phthalic acid, benzoic
      acid, 1, 4-dihydroxyanthraquinone, and 2,3-dihydro-9,10-dihydroxy-1,4
      anthracenedione) were identified by running HPLC grade standards in defined
      concentrations. The retention time of the compounds were 2.0, 2.5, 5.2, and 7.2
      min for phthalic acid, benzoic acid, 1, 4-dihydroxyanthraquinone, and 2,3-dihydro
      9,10-dihydroxy-1,4-anthracenedione, respectively. The reliability, sensitivity,
      and validation of the method were checked by calculating recoveries of the
      individual compounds in the acetonitrile and dye degradation media. The lower
      limits of detection for anthraquinone metabolites and the separation of acid and
      anthraquinone metabolites in short time were achieved.

PMID- 20680443
TI  - Relationship of age to body weight, scrotal circumference, testicular
      ultrasonograms, and semen quality in Sahiwal bulls.
AB  - The objective of the present study was to determine the relationship of age to
      body weight (BW), scrotal circumference (SC), number of pixels of testicular
      ultrasonograms (NP), and semen quality in Sahiwal bulls. The study was based on
      128 Sahiwal bulls of different age groups (from 0 to >100 months of age). Bulls
      were evaluated for SC, BW, and NP. Semen was evaluated once a week for five
      consecutive weeks from regularly collected donor bulls (n = 86) ranging in age
      from 25-30 to >100 months. Ejaculate volume, sperm motility, sperm concentration,
      sperm morphology, percent live sperms, sperm plasma membrane integrity, and
      normal acrosome were compared among different age groups. Mean SC and BW
      increased (P < 0.05) in a curvilinear manner from birth to >100 months of age.
      Mean NP of testicular ultrasonograms increased (P < 0.05) from 0 to 24 months and
      then plateaued until >100 months of age. Body weight, SC, and NP were positively
      correlated with age from birth until >100 months (r = 0.91, 0.87, and 0.40,
      respectively). Ejaculate volume (5.7 +/- 0.2 vs. 4.6 +/- 0.09 ml) and sperm
      concentration (1,281.6 +/- 17.7 vs. 1,115.8 +/- 55.9 * 10(6)/ml) increased (P <
      0.05) in mature bulls compared to younger ones. However, motility (68.6 +/-
      0.3%), plasma membrane integrity (50.8 +/- 1.0%), and normal acrosome (74.8 +/-
      0.5%) remained insignificant due to age. In six of eight age groups studied,
      morphological abnormalities were well within the range (18.1 +/- 0.3%). In
      conclusion, the BW, SC, and NP of testicular ultrasonograms, ejaculate volume,
      and concentration increased with age. Moreover, semen quality is fairly
      independent of age except volume and concentration in Sahiwal bulls.

PMID- 20680442
TI  - Granulocyte colony-stimulating factor for ischemic heart failure: should we use
      it?
AB  - Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic cytokine usually
      used in the treatment of patients with cancer. Studies have shown regenerative
      properties of bone marrow stem cell mobilization due to G-CSF in animals.
      Moreover, others effects related to G-CSF and independent of tissue regeneration
      were shown to be protective. As a result, this cytokine has been tested as a
      therapy for ischemic heart failure in humans. However, when this treatment was
      evaluated in clinical trials, the beneficial effects seen in small animals were
      not confirmed in infarcted patients. Thus, we sought to review the effects of G
      CSF after an ischemic insult and on the progression of heart failure in animals
      and humans.

PMID- 20680444
TI  - Phylogenetic background and virulence genes of Escherichia coli isolates from
      colisepticemic and healthy broiler chickens in Iran.
AB  - The purposes of this study were to determine the phylogenetic background and the
      virulence gene profiles of Escherichia coli isolates from colisepticemic and
      feces of healthy (AFEC) broiler chickens. In this study, 253 E. coli isolates
      including 141 avian pathogenic E. coli (APEC) and 112 AFEC isolates were examined
      by PCR. In general, 253 E. coli isolates distributed among group A (51.8%), B1
      (15.8%), B2 (8.7%), and D (23.7%). Ten (8.9%) AFEC isolates segregated in to B1
      phylo-group and 102 (91.1%) isolates fell into six different phylogenetic
      subgroups. Distribution of colisepticemic and fecal isolates differed
      significantly in their assignments to A and B1 phylo-groups. The three most
      prevalent virulence genes were crl, fimH, and aer in isolates between both
      groups. The four genetic markers aer, papC, afa, and sfa were detected
      significantly more often among colisepticemic isolates than in fecal isolates
      from healthy broilers. The presence of stx ( 2 ) gene in fecal isolates were
      significantly differs among the colisepticemic isolates. F17 fimbrial family
      encoding gene and eae gene were detected in APEC and AFEC isolates, respectively.
      The colisepticemic and fecal isolates possessed the virulence genes were detected
      in all of the four phylogenetic groups. Several combination patterns of the
      virulence genes were detected in APEC and AFEC isolates. In colisepticemic
      isolates the combination of aer, crl, and fimH genes was the most prevalent
      pattern. None of the examined isolates harbored the cdt, cnf1, ipaH, and stx ( 1
      ) virulence gene sequences.

PMID- 20680445
TI  - Skin and coat traits in sheep in Brazil and their relation with heat tolerance.
AB  - The objective of this study was to evaluate and compare physical parameters in
      groups of sheep with different phenotypic characteristics in the Centre-west
      region of Brazil. Five groups of sheep, with nine animals per group, were
      selected, three groups of Santa Ines animals with different coat colours (white,
      brown and black), one group with crossbred animals (Santa Ines * Bergamasca) and
      one group with animals of the Bergamasca breed. The following traits were
      evaluated: coat thickness, number and length of hair, pigmentation level in the
      coat and the skin as well as the percentage area of sweats glands in the skin
      tissue, carried out by histological analysis. The number of hairs and the area of
      sweats glands were not significantly different between the evaluated groups. The
      Bergamasca breed showed low pigmentation of the skin and long hairs. The levels
      of pigmentation of the hair and of the skin were highly correlated. Between the
      Santa Ines groups, the group with white hair showed the better parameters for
      heat adaptation, while the brown hair group showed the lower heat adaptation when
      compared with another hair breed groups.

PMID- 20680446
TI  - Prevalence and molecular diagnosis of Trypanosoma evansi in Nili-Ravi buffalo
      (Bubalus bubalis) in different districts of Punjab (Pakistan).
AB  - The prevalence of Trypanosoma evansi was investigated in 1,250 Nili-Ravi
      buffaloes of mixed age and sex by polymerase chain reaction (PCR) for the first
      time in Pakistan. DNA of the trypanosomes was isolated with TRIREAGENT(r). The
      assay was employed using primers ESAG 6/7, specific for a 237-bp fragment from T.
      evansi genomic DNA. The samples were screened for the presence of T. evansi also
      by stained thin smear. Forty-four (3.5%) samples were positive by microscopy,
      while 97 (7.7%) samples were identified by PCR, indicating the high sensitivity
      of PCR for surveying the disease in epidemiological studies.

PMID- 20680447
TI  - Change of semen quality after foreign travel: a rare presentation of genital
      schistosomiasis.

PMID- 20680448
TI  - Reconstructive surgery for tuberculous contracted bladder: experience of a center
      in northern India.
AB  - OBJECTIVE: To document the management of tuberculous cicatrized urinary bladder
      by incorporating bowel segment and the long-term follow-up after the
      reconstructive surgery. MATERIALS AND METHODS: Twenty-three patients (out of 28)
      were managed by augmentation cystoplasty (AC) and 5 by orthotopic neobladder
      (OTN) reconstruction. Sigmoidocystoplasty was performed in 11 cases,
      ileocystoplasty in 10 patients and ileocecocystoplasty in 2 patients. Ileal
      neobladder reconstruction was done in 2 patients, ileocecal neobladder
      reconstruction in 1 patient and sigmoid neobladder reconstruction in 2 patients,
      respectively. The patients were followed according to standard follow-up
      protocols. RESULT: The mean age of patients who underwent AC was 32.5 years and
      of those who underwent OTN reconstruction was 31 years. The mean pre-operative
      bladder capacity in patients with AC was 70 ml (range 40-100 ml) and of patients
      with OTN reconstruction was 14 ml (range 10-20 ml). The mean postoperative
      bladder capacity at 3 months following AC was 427 ml (range 450-500 ml) and
      following OTN reconstruction it was 430 ml (range 350-450 ml). The mean follow-up
      in patients who underwent AC was 43.3 months (range 12-90 months) and in those
      who underwent OTN reconstruction it was 35.6 months (16-60 months). None of the
      patients had upper urinary tract deterioration following the reconstructive
      surgery. CONCLUSION: Urinary bladder rehabilitation either by AC or OTN
      reconstruction increases the bladder capacity and storage time and also preserves
      the upper tracts.

PMID- 20680449
TI  - Laparoscopic partial nephrectomy for tumours >4 cm compared with smaller tumours:
      perioperative results.
AB  - OBJECTIVE: The use of laparoscopic partial nephrectomy (LPN) in patients with
      tumours >4 cm remains to be further evaluated. We report our experience with LPN
      in tumours >4 cm compared with tumours <=4 cm. MATERIALS AND METHODS: This is a
      retrospective study of data from all LPN patients operated from 2003 to 2008.
      Inclusion criteria were a single organ confined contrast enhancing mass/Bosniac
      III-IV cyst. Hospital admission records were used to extract operative and follow
      up data. Patients were grouped into group A: <=4 cm (32 patients, 53% of total),
      and group B: >4 cm (28 patients, 47% of total). RESULTS: A total of 60 patients
      (mean +/- SD age, 47.4 +/- 13.4 years; M/F, 36/24) were included. Mean +/- SD
      tumour size was 31.5 +/- 7.3 mm and 51.6 +/- 10.9 mm in groups A and B,
      respectively. (P < 0.001) Malignant pathology was present in 22 (69%) and 16
      patients (57%) in groups A and B, respectively. (P > 0.05) There was no
      statistically significant difference in age, gender, pre-operative creatinine,
      estimated glomerular filtration rate (eGFR), and other investigated pre-operative
      characteristics between study groups. (all P > 0.05) Nor any difference was
      observed regarding operative and pathologic (warm ischaemia time, operation
      duration, transfusion, positive margins, and malignant histology) as well as post
      operative variables (re-hospitalization, post-operative complications, hospital
      stay, or eGFR changes). CONCLUSION: The results of this study supports the
      feasibility and comparability of operative and post-operative early complications
      for LPN when applied to tumours >4 cm in selected patients compared with tumours
      <=4 cm.

PMID- 20680450
TI  - Sexual dysfunction in type III chronic prostatitis (CP) and chronic pelvic pain
      syndrome (CPPS) observed in Turkish patients.
AB  - AIM: Chronic prostatitis (CP) and chronic pelvic pain syndrome (CPPS) is a common
      disabling condition that is primarily associated with pain in the urogenital
      region and disturbances in urinary and sexual function. Chronic pelvic pain
      symptoms are the most common presentation, especially perineal, lower abdominal,
      testicular, penile as well as ejaculatory pain. Other genitourinary tract
      complaints include voiding disorders and sexual dysfunction. We aimed in the
      study at examining the prevalence rates of premature ejaculation and erectile
      dysfunction in patients with chronic pelvic pain syndrome and comparing these
      rates with those of healthy control subjects. MATERIALS AND METHODS: Between
      November 2006 and January 2008, 85 patients with the diagnosis of CP/CPPS were
      chosen for the study; 30 patients without regular sexual activity and 12 patients
      without inclusion criteria were excluded from the study. A total of 43 patients
      were included in the study. Twenty healthy volunteers without prostatitis-like
      syndromes were used as a control group. The sexual function of the patients and
      the healthy volunteers were evaluated using Arizona Sexual Function Questionary
      Form and International Index of Erectile Function (IIEF). Erectile dysfunction
      (ED), ejaculatio precox (EP) and pain on ejaculation (PEP) were investigated as
      sexual dysfunction. RESULTS: The mean age of the patients was 33.7 (22-48) years;
      the mean symptom period was 37.7 (6-120) months, while the mean age of the
      control group was 32.4 (24-48) years. The mean NIH-CPSI score of the patient
      group was 26.1 (16-34). Patient group was classified as CPPS type IIIa and CPPS
      type IIIb. Mild and moderate erectile dysfunction (ED) was found in [9] 23.2%
      patients at the patient group and [2] 10% at the control group (P: 0.185). Severe
      erectile dysfunction was not found in both groups. Ejaculatio Precox (EP) was
      found at (29) 67.4% of the patient group and [7] 40% of the control group. Pain
      on ejaculation (PEP) was detected in [15] 37.2% of the patient group, while none
      of the control group had pain on ejaculation. More than one sexual dysfunction
      was found in [17] 41.8% of the patient group and none of the control group.
      Comparing patient group versus control group, ejaculation disorders (EP and PEP)
      and more than one sexual dysfunction disorder were statistically significant.
      According to ED, there is no statistical difference between the groups (P >
      0.05). CONCLUSION: Sexual function disorders, especially ejaculation disorders
      (EP and PEP), are frequently seen in CP/CPPS patients versus normal population.
      Age, symptoms period, symptom score and CP/CPPS subgroups are not risk factors
      for sexual function disorders. Patients with the diagnosis of CP/CPPS should be
      evaluated for sexual function disorders.

PMID- 20680451
TI  - Urinary tract infection before and after mid-urethral slings: culture-proven
      diagnosis and analysis of risk factors.
AB  - OBJECTIVES: To study prevalence of UTI in women with SUI before and after mid
      urethral slings based on culture-proven diagnosis. MATERIALS AND METHODS: Clean
      catch midstream urine samples were collected and sent for agar culture in 150
      patients before and on follow-up after mid-urethral slings visit. Degree of
      agreement between culture-proved UTI and clinically suspected was assessed. In
      addition, risk factors for UTI were analyzed. RESULTS: Preoperative culture was
      positive in 9 (6%) patients, 7 of them were asymptomatic. UTI was primarily
      diagnosed in 39 (26%) patients suggested by symptoms. No bacterial growth was
      detected at first postoperative day. There were 6 out of 62 (9.7%) patients who
      had positive urine cultures at follow-up visits, all of them were symptomatic.
      Eleven (18%) patients were diagnosed as UTI, based on clinical suspicion.
      CONCLUSION: In contrast to UTI before surgery, asymptomatic UTI is unlikely to
      happen after mid-urethral sling.

PMID- 20680452
TI  - Criminal justice involvement of individuals with severe mental illness and
      supported employment outcomes.
AB  - This study examined the impact of criminal justice involvement on competitive
      employment outcomes for clients with severe mental illness enrolled in supported
      employment. Based on chart reviews of 154 clients enrolled in supported
      employment, the CJI and no CJI groups differed on several clinical and
      demographic variables, but did not differ on competitive employment outcomes.
      This study suggests that clients with criminal justice involvement do benefit
      from supported employment. Further research should track employment outcomes for
      a longer interval with a larger study group in order to provide a more complete
      picture of the extent to which CJI impacts employment.

PMID- 20680453
TI  - Immigration, acculturation and chronic back and neck problems among Latino
      Americans.
AB  - Higher acculturation is associated with increased obesity and depression among
      Latino-Americans, but not much is known about how acculturation is related to
      their prevalence of back and neck problems. This study examines whether
      acculturation is associated with the 12-month prevalence of self-reported chronic
      back or neck problems among US-born and immigrant Latinos. We performed
      multivariable logistic regression analysis of data from 2,553
      noninstitutionalized Latino adults from the 2002-2003 National Latino and Asian
      American Survey (NLAAS). After adjusting for demographic, physical and mental
      health indicators, English proficiency, nativity and higher generational status
      were all significantly positively associated with the report of chronic back or
      neck problems. Among immigrants, the proportion of lifetime in the US was not
      significantly associated. Our findings suggest that the report of chronic back or
      neck problems is higher among more acculturated Latino-Americans independent of
      health status, obesity, and the presence of depression.

PMID- 20680454
TI  - 75 years after mining ends stream insect diversity is still affected by heavy
      metals.
AB  - A century of heavy metal mining in the western United States has left a legacy of
      abandoned mines. While large operations have left a visible reminder, smaller one
      and two-man operations have been overgrown and largely forgotten. We revisited an
      area of northern Idaho that has not had active mining since at least 1932 and
      probably since 1910. At three sites along each of 10 mountain streams we sampled
      larval stream insects and correlated their community diversity to stream levels
      of arsenic, cadmium, lead, zinc, pH, temperature, oxygen content, and
      conductivity. Although the streams appear pristine, multivariate statistics
      indicated that cadmium and zinc levels were significantly correlated with fewer
      animals, fewer families, a smaller percentage of plecopterans (stoneflies), and
      lower Shannon H diversity values. After at least 75 years, abandoned mines appear
      to be still influencing stream communities.

PMID- 20680455
TI  - Body condition and mercury concentration in apparently healthy Goosander (Mergus
      merganser) wintering in the Odra estuary, Poland.
AB  - Goosanders (Mergus merganser, ad, adult n = 42: M, males 33 and F, females 9; im,
      immature n = 17: M 8, F 9) were collected in 2005 at wintering site in the River
      Odra estuary (Poland). The body size (BM, body mass; BL, body length; KL, keel
      length), weights of organs (LM, liver; KM, kidneys; EM, encephalon), and two
      condition-related indices (BM/BL and BM/KL) were determined. Based on BM/BL and
      BM/KL indices, the birds were divided into 3 condition groups: A (very good), B
      (good), and C (moderate). Total mercury (Hg) concentrations (mg kg(-1) dry
      weight) were determined in liver, kidney, brain, breast muscle, and bone of 17
      birds (ad, n = 8: 8 M, 1 F; im, n = 9: 6 M, 3 F). The highest Hg concentrations
      (in n = 17) were recorded in liver and kidney (14.7 and 9.9 mg kg(-1),
      respectively); the concentrations found in muscle and brain were lower (2.3 and
      1.3 mg kg(-1), respectively), the lowest concentrations being typical of bone
      (0.08 mg kg(-1)). Mercury concentrations in the same organs of immature and adult
      goosanders, as well as males and females, did not differ significantly. On the
      other hand, distinct differences in Hg concentrations in the organs studied
      (except for the liver) were observed between individuals assigned to Group A (n =
      11) and C (n = 6). Mercury levels were higher in the birds characterised by very
      good condition, which was most probably related to those birds being more
      efficient hunters, consuming higher amounts of Hg-containing fish. Significant
      and negative correlations between the muscle Hg concentration and the two
      condition-related indices (r > -0.70) were recorded in Group A only: the higher
      the concentration, the lower the BM/LM and BM/KL values.

PMID- 20680456
TI  - Growth response of the duckweed Lemna gibba L. to copper and nickel
      phytoaccumulation.
AB  - To assess the tolerance and phytoaccumulation ability of the duckweed Lemna gibba
      L. to copper (Cu) and nickel (Ni), the plants were exposed to different
      concentrations of Cu and Ni (0.1-2.0 mg/l) under laboratory conditions. The
      results showed that Cu and Ni were tolerated by L. gibba at concentrations <=0.3
      and <=0.5 mg/l, respectively. However, plant growth decreased by 50% (I(50)) when
      the medium contained 0.45 mg Cu/l or 0.75 mg Ni/l. The observed LCI (lowest
      concentration causing complete inhibition) were 0.5 and 1.0 mg/l respectively in
      the presence of Cu and Ni. Results from metal analysis in plant biomass revealed
      a high accumulation of Cu (1.5 mg g(-1) DW), a low accumulation of Ni (0.5 mg g(
      1) DW) within the plants and a corresponding decrease of metals in the water. The
      removal percentage of Cu was about 60-80%. We conclude that the duckweed L. gibba
      L. showed a higher accumulation potential for Cu from polluted water than Ni
      after 4 days of exposure.

PMID- 20680457
TI  - Mitotic figures in the median eminence of the hypothalamus.
AB  - The median eminence of the hypothalamus is part of the avenue by which
      neurosecreted hormones from the hypothalamic nuclei reach the pars nervosa
      (neural lobe) of the pituitary and eventually the bloodstream. Lithium treatment
      and osmotic stress increases the transport of neurosecretory hormones to the
      pituitary in the adult rat. Specialized astrocytes termed pituicytes in the pars
      nervosa of the pituitary participate in the secretory process and also develop
      considerable mitotic activity. The present work reveals similar mitotic figures
      in cells within the median eminence following 3 days of lithium treatment. The
      location and appearance of these mitoses add to the evidence that pituicytes are
      present in the median eminence. Moreover, mitoses occur within the ependymal
      (tanycyte) layer of the median eminence. Thus, the present results suggest that
      the tanycyte layer may contain pituicytes, indicating that the hypothalamus
      possesses specialized cells for modulating neurosecretion in response to osmotic
      challenges.

PMID- 20680458
TI  - Primary cultures from cerebral cortex and hippocampus enriched in glutamatergic
      and GABAergic neurons.
AB  - The aim was to define a primary culture system enriched in neurons using a
      defined culture medium, and characterize the model system as to cellular
      morphology and neuronal phenotypes. We found that these primary neuron enriched
      cultures from either newborn rat cerebral cortex or hippocampus contain small
      GABAergic and large glutamatergic neurons as well as astrocytes and microglia.
      Astrocytes in these cultures are morphologically differentiated with long,
      slender processes and interact with soluble factors responsible for induction and
      expression of the glutamate transporter GLT-1. The cultures achieve the highest
      expression of the vesicular glutamate transporter 1 (VGLUT1) and GLT-1 after 20
      days in vitro. Conditioned media from these neuron enriched cultures also induced
      GLT-1 expression in primary astrocytic cultures, which were free from neurons.
      The amount of glutamatergic neurons guides the morphological maturation of
      astrocytes and GLT-1 expression both in the neuron enriched cultures and in the
      conditioned media supplemented astrocytic cultures. Interestingly, these cultures
      were not influenced or activated by the inflammatory stimulus lipopolysaccharide.
      This suggests that soluble factors from neurons protect microglia and astrocytes
      to become inflammatory reactive. In conclusion we have developed a well
      characterized culture model system enriched in neurons, taken from newborn rats
      and cultured in defined media. The neurons express different neuronal phenotypes.
      Such a model system is valuable when studying interactions between neurons and
      glial cells.

PMID- 20680459
TI  - Oroxylin A, a flavonoid, stimulates adult neurogenesis in the hippocampal dentate
      gyrus region of mice.
AB  - Previously, we reported the cognitive enhancing effects of oroxylin A in
      unimpaired mice and its memory ameliorating activity in various memory impaired
      mice. To elucidate the mechanism mediating the cognitive effects of oroxylin A,
      this study examined the consequences of oroxylin A administration on neurogenesis
      in the hippocampal dentate gyrus using immunostaining for 5-bromo-2-deoxyuridine
      (BrdU) incorporation. In addition, we determined whether the new cells adopted a
      neuronal or glial fate by examining the co-localization of BrdU staining with
      neuronal or glial markers. Administration of oroxylin A in a dose-dependent and
      time-dependent manner increased the number of BrdU-incorporating cells. Moreover,
      the percentage of BrdU-incorporating cells co-localized with neuronal markers,
      neuronal nuclei, was significantly increased by the oroxylin A administration.
      These results suggest that the increased neurogenesis induced by the
      administration of oroxylin A could be, at least in part, associated with its
      positive effects on cognitive processing.

PMID- 20680460
TI  - Differential patterns of alcohol consumption and dopamine-2 receptor binding in
      Wistar-Kyoto and Wistar rats.
AB  - The Wistar-Kyoto (WKY) rat strain has been described as an animal model of
      depressive behavior that consumes significantly greater amounts of alcohol
      compared to the Wistar (WIS) rat strain. Since the mesolimbic dopamine (DA) type
      2 (D2) receptors mediate reward-related behaviors, the present study measured the
      binding of [(125)I]-Iodosulpiride to D2 receptors in the brains of WKY versus WIS
      rats following 24 days of voluntary alcohol or water consumption. Alcohol
      consuming WKY rats showed a significant increase in D2 receptor binding in
      several regions of the mesolimbic and nigrostriatal systems. In contrast, alcohol
      consuming WIS rats showed a reduction in D2 receptor binding in DA cell body
      areas. The differential regulation of D2 receptors by voluntary alcohol
      consumption in the two rat strains suggests that D2 receptor mediated
      neurotransmission may be playing a role in the increased alcohol drinking
      behavior reported in WKY rats.

PMID- 20680461
TI  - Imbalance between nitric oxide and dopamine may underly aggression in acute
      neurological patients.
AB  - The neurochemical basis of aggressive behavior in humans is not fully understood.
      In this study we explored the relationship between aggressiveness (as measured by
      the Overt Aggression Scale), cognitive performance (as measured by the Mini
      Mental State Examination), and biochemical markers of dopamine neurotransmission
      (homovanillic acid, HVA) and nitric oxide synthesis (nitrite plus nitrate, NO(x))
      in cerebrospinal fluid from 70 patients with acute brain disorders, mainly brain
      infections. Aggressive behavior and cognitive performance showed an inverse
      correlation. NO(x)/HVA ratio was inversely correlated to aggressive behavior, and
      positively correlated to cognitive performance. A subanalysis with antipsychotic
      naive patients confirmed those results. The balance between nitric oxide and
      dopamine could be related to the cognitive control of aggressive impulse.

PMID- 20680462
TI  - Low-dose coronary computed tomography angiography using prospective ECG
      triggering compared to invasive coronary angiography.
AB  - To assess the diagnostic accuracy of prospective ECG-triggering 64-slice
      multidetector computed tomography (MDCT) coronary angiography for evaluation of
      coronary artery disease (CAD). Forty-two patients (31 males, 11 females, mean age
      64 years) underwent cardiac CT and invasive coronary angiography (ICA). Patients
      with a heart rate of <65 beats/min with stable heart rhythm were included in the
      study sample. We used a prospective ECG-triggering protocol. Luminal narrowing
      over 50% was considered to be significant according to a modified 17-segment AHA
      model, using invasive coronary angiography (ICA) as the standard of reference.
      The mean radiation dose was 3.5 mSv +/- 0.3 (range, 3.3-4.2 mSv), and 542 of 549
      segments (98.7%) in the 42 patients were diagnostic. In contrast, 119 of 542
      segments (22%) were diagnosed as significant by ICA. The sensitivity,
      specificity, accuracy, PPV and NPV were 95.0, 96.2, 96, 85.8 and 98.8%,
      respectively. False positive results were affected by densely calcified plaques,
      whereas false negatives were caused by motion artifact with poor vessel
      attenuation at the distal segments or near the bifurcation area of the coronary
      arteries. Prospective ECG-triggering MDCT is a useful method for evaluating CAD
      in patients with a lower heart rate with low radiation dose.

PMID- 20680463
TI  - Microfluidic sedimentation cytometer for milk quality and bovine mastitis
      monitoring.
AB  - We report a rapid, low-cost, portable microfluidic sedimentation cytometer (SeCy)
      for assessing the somatic cell count and fat content of milk in 15 min using a
      "sample-in, answer-out" approach. The system consists of 12 independent
      microfluidic devices, essentially flattened funnel structures, fabricated on the
      footprint of a single plastic compact disc (CD). Each funnel structure holds 150
      MUL of milk, has an inlet for milk filling and an outlet for air to escape, and
      ends in a narrow, closed-end microfluidic channel that facilitates packing of the
      cells into a column whose length is proportional to cell count. The closed-end
      channel provides accurate cell counts over the range 50,000->3,000,000 cells per
      mL. The assay separates cells and fat globules based on their densities (by
      differential sedimentation), concentrating white cells in the closed-end channel
      near the outer rim of the CD for estimation of total "cell pellet" volume, while
      fat globules move toward the center of disc rotation, forming a fat "band" in the
      funnel. After adding milk to two or more microfluidic devices, the CD is loaded
      onto a custom-built reader unit that spins the disc for 15 min. Two low-cost
      microscopes in the reader image the centrifuged cell pellet and the fat band,
      providing a sufficiently accurate cell count to diagnose mastitis and measuring
      fat content as an indication of health and nutritional status.

PMID- 20680464
TI  - MnHSP90 cDNA characterization and its expression during the ovary development in
      oriental river prawn, Macrobrachium nipponense.
AB  - Heat shock protein 90 (HSP90) is not only involved in environmental stress but
      also plays roles in the ovary development in some vertebrates. To understand its
      role in crustacean, we examined the HSP90 cDNA for the first time in the ovary
      and hepatopancreas of the oriental river prawn, Macrobrachium nipponense and
      designated this protein as MnHSP90 in this study. The MnHSP90 was cloned by the
      methods of degenerated oligonucleotide primers and rapid amplification of the
      cDNA ends (RACE). Bioinformatics analysis showed that the MnHSP90 cDNA was 2,684
      bp in length, containing a 126 bp 5' untranslated region (UTR), a 359 bp 3' UTR,
      and an open reading frame (ORF) of 2,199 bp encoding a 732-amino acid polypeptide
      with predicted molecular mass of 84.3 KDa. Sequence alignment showed that the
      MnHSP90 shared 72-79% identity with other animals. Real-time quantitative PCR
      (qPCR) analysis demonstrated that the MnHSP90 mRNA was ubiquitously detected in
      all tested tissues, with the highest expression in the thoracic ganglia, the
      mediate in heart, muscle and intestine, and the lowest in haemocytes and gills.
      The MnHSP90 mRNA levels in the hepatopancreas and ovary of M. nipponense reached
      a maximum at the stage III (early vitellogenic stage) and stage IV (later
      vitellogenic stage) ovaries, respectively, and then decreased significantly in
      both tissues as the ovarian development proceeded. The level of MnHSP90
      expression in the hepatopancreas was higher than that in the ovary when compared
      with in the same ovarian developmental stage. Our results indicate that MnHSP90
      is involved in ovarian development in oriental river prawn and may play a
      regulatory role in ovary maturation.

PMID- 20680465
TI  - AC3-33, a novel secretory protein, inhibits Elk1 transcriptional activity via ERK
      pathway.
AB  - The transcription factor AP-1 plays an important role in cellular proliferation,
      transformation and death. In this study, we report a novel human gene, AC3-33
      (GenBank name: c3orf33, FLJ31139), which encodes a secretory protein that can
      inhibit Elk1 transcriptional activity via ERK1/2 pathway. The AC3-33 mRNA encodes
      a protein of 251 amino acids, which is a classical secretory protein. Functional
      investigation reveals that overexpression of AC3-33 significantly inhibit AP-1
      activity and DNA-binding ability. Further investigation indicated that
      overexpression of AC3-33 significantly inhibit transcriptional activity of Elk1
      and c-jun, but not c-fos. As for the upstream of signaling pathway of Elk-1, our
      study demonstrated that overexpression of AC3-33 significantly down-regulates
      phosphorylation of ERK1/2, but not JNK/SAPK or p38 MAPK. These results clearly
      indicate that AC3-33 is a novel member of the secretory family and inhibits Elk1
      transcriptional activity via ERK1/2 MAPK.

PMID- 20680466
TI  - Measuring cost efficiency in the Nordic hospitals--a cross-sectional comparison
      of public hospitals in 2002.
AB  - The aim of this study was to compare the performance of hospital care in four
      Nordic countries: Norway, Finland, Sweden and Denmark. Using national discharge
      registries and cost data from hospitals, cost efficiency in the production of
      somatic hospital care was calculated for public hospitals. Data were collected
      using harmonized definitions of inputs and outputs for 184 hospitals and data
      envelopment analysis was used to calculate Farrell efficiency estimates for the
      year 2002. Results suggest that there were marked differences in the average
      hospital efficiency between Nordic countries. In 2002, average efficiency was
      markedly higher in Finland compared to Norway and Sweden. This study found
      differences in cost efficiency that cannot be explained by input prices or
      differences in coding practices. More analysis is needed to reveal the causes of
      large efficiency disparities between Nordic hospitals.

PMID- 20680467
TI  - The language of medicine and bioethics.

PMID- 20680469
TI  - The cultural context of patient's autonomy and doctor's duty: passive euthanasia
      and advance directives in Germany and Israel.
AB  - The moral discourse surrounding end-of-life (EoL) decisions is highly complex,
      and a comparison of Germany and Israel can highlight the impact of cultural
      factors. The comparison shows interesting differences in how patient's autonomy
      and doctor's duties are morally and legally related to each other with respect to
      the withholding and withdrawing of medical treatment in EoL situations. Taking
      the statements of two national expert ethics committees on EoL in Israel and
      Germany (and their legal outcome) as an example of this discourse, we describe
      the similarity of their recommendations and then focus on the differences,
      including the balancing of ethical principles, what is identified as a problem,
      what social role professionals play, and the influence of history and religion.
      The comparison seems to show that Israel is more restrictive in relation to
      Germany, in contrast with previous bioethical studies in the context of the moral
      and legal discourse regarding the beginning of life, in which Germany was
      characterized as far more restrictive. We reflect on the ambivalence of the
      cultural reasons for this difference and its expression in various dissenting
      views on passive euthanasia and advance directives, and conclude with a comment
      on the difficulty in classifying either stance as more or less restrictive.

PMID- 20680470
TI  - A functional varient in microRNA-146a is associated with risk of esophageal
      squamous cell carcinoma in Chinese Han.
AB  - MicroRNAs are a new class of non-proteincoding, small RNAs that function as tumor
      suppressors or oncogenes. They participate in diverse biological pathways and
      function as gene regulators. A G>C polymorphism (rs2910164), which is located in
      the sequence of miR-146a precursor, results in a change from G:U to C:U in its
      stem region. However, it remains largely unknown whether this single nucleotide
      polymorphism (SNP) may alter esophageal squamous cell carcinoma (ESCC)
      susceptibility. In the current study, we evaluated association between rs2910164
      and ESCC susceptibility in a case-control study of 444 sporadic ESCC patients and
      468 matched cancer-free controls in a Chinese Han population. Compared with
      rs2910164 variant genotype CC, genotype GG was associated with increased risk of
      ESCC (Odds Ratio, 2.39, 95% Confidence Interval, 1.36-4.20). In the smokers, the
      risk of rs2910164 GG genotype was more notable (Odds Ratio, 3.17, 95% Confidence
      Interval, 1.71-4.46). In the stratification analyses, we also found there was a
      strong correlation between rs2910164 C/G variant and the clinical TNM stage (P <
      0.01). These findings suggest that this functional SNP in pre-miR-146a could
      contribute to ESCC susceptibility and clinical outcome.

PMID- 20680471
TI  - Effects of moderate hypobaric hypoxic preconditioning on the expression of the
      transcription factors pCREB and NF-kappaB in the rat hippocampus before and after
      severe hypoxia.
AB  - Preconditioning using three sessions of moderate hypobaric hypoxia, i.e., hypoxic
      preconditioning (HP), increased the tolerance of susceptible brain neurons to
      severe hypoxia and other harmful factors. The study addressed changes in the
      expression of transcription factors NF-kappaB (nuclear factor kappa B) and CREB
      (cAMP response element binding protein) in the hippocampus of rats preconditioned
      with moderate hypoxia. Immunocytochemical methods demonstrated that HP increased
      immunoreactivity for NF-kappaB and phosphorylated CREB (pCREB) in hippocampal
      fields CA1-CA4 and the dentate gyrus and promoted increases in the expression of
      these transcription factors in the hippocampus of preconditioned rats 3-24 h
      after severe hypobaric hypoxia. These data provide evidence that NF-kappaB and
      CREB are involved in the mechanisms forming HP-induced tolerance of the brain.

PMID- 20680472
TI  - Neuron division or enucleation.
AB  - The classical Bielschowsky-Gross neurohistological method was used to reproduce
      all the morphological phenomena interpreted by many authors as signs of neuron
      division, budding, and fission. It is suggested that these signs are associated
      with the effects of enucleation, which occurs in many cells of other tissue types
      in response to a variety of chemical and physical treatments. Studies were
      performed using neurons isolated from the mollusk Lymnaea stagnalis and exposed
      in tissue culture to the actin microfilament inhibitor cytochalasin B. Phase
      contrast time-lapse video recording over periods of 4-8 h demonstrated nuclear
      displacement, ectopization, and budding, to the level of almost complete fission
      of the neuron body. This repeats the pattern seen in static fixed preparations in
      "normal" conditions and after different experimental treatments. Budding of the
      cytoplasm was also sometimes seen at the early stages of the experiments. Control
      experiments in which cultured neurons were exposed to the solvent for
      cytochalasin B, i.e., dimethylsulfoxide (DMSO), did not reveal any changes in
      neurons over a period of 8 h. We take the view that the picture previously
      interpreted as neuron division and fission can be explained in terms of the
      inhibition of actin microfilaments, sometimes developing spontaneously in cells
      undergoing individual metabolic changes preventing the maintenance of
      cytoskeleton stability.

PMID- 20680473
TI  - The role of cholesterol in the exo- and endocytosis of synaptic vesicles in frog
      motor nerve endings.
AB  - Experiments on frog neuromuscular preparations using electrophysiological (two
      electrode voltage clamping) and optical (with the fluorescent endocytic stain FM1
      43) methods were performed to study the importance of membrane cholesterol in the
      exo- and endocytic cycle of synaptic vesicles (SV) in motor nerve endings in
      conditions of prolonged rhythmic stimulation of the motor nerve (20 impulses/sec,
      3 min). Extraction of cholesterol from the superficial plasma membranes using
      methyl-beta-cyclodextrin (1 mM) led to marked changes in SV recycling. There was
      weakening of SV exocytosis and suppression of processes leading to the recovery
      of SV populations with rapid readiness to release neurotransmitter. When
      cholesterol was leached from the outer membranes and the membranes of SV
      undergoing recycling, these effects were supplemented by impairments to SV
      endocytosis and recycling. Thus, plasma membrane cholesterol plays a key role in
      the processes of exocytosis, while the efficiency of endocytosis depends on
      cholesterol in SV membranes.

PMID- 20680474
TI  - Local GABAergic modulation of the activity of serotoninergic neurons in the
      nucleus raphe magnus.
AB  - Experiments on rat brainstem sections in membrane potential clamping conditions
      addressed the effects of serotonin and GABA on serotoninergic neurons in the
      nucleus raphe magnus. Local application of serotonin stimulated inhibitory
      postsynaptic currents (IPSC) in 45% of the serotoninergic neurons studied. This
      response was not seen in the presence of the fast sodium channel blocker
      tetrodotoxin. The GABAA receptor antagonist gabazine blocked IPSC in both
      serotonin-sensitive and serotonin-insensitive neurons. Application of GABA evoked
      generation of a membrane current (IGABA), which was completely blocked by
      gabazine. These results indicate self-regulation of the activity of
      serotoninergic neurons in the nucleus raphe magnus via a negative feedback
      circuit involving local GABAergic interneurons.

PMID- 20680475
TI  - Influence of music with different volumes and styles on recognition activity in
      humans.
AB  - The efficiency of the recognition of masked visual images (Arabic numerals)
      increased when accompanied by classical (62 dB) and rock music (25 dB). These
      changes were accompanied by increases in the coherence of potentials in the
      frontal areas seen on recognition without music. Changes in intercenter EEG
      relationships correlated with the formation a dominant at the behavioral level.
      When loud music (85 dB) and music of other styles was used, these changes in
      behavior and the EEG were not seen; however, the coherence of potentials in the
      temporal and motor cortex of the right hemisphere increased and the latent
      periods of motor reactions of the hands decreased. These results provide evidence
      that the "recognition" dominant is formed when there are particular ratios of the
      levels of excitation in the corresponding centers, which should be considered
      when there is a need to increase the efficiency of recognition activity in
      humans.

PMID- 20680476
TI  - Effects of weak electromagnetic irradiation on various types of behavior in the
      mealworm Tenebrio molitor.
AB  - The effects of weak electromagnetic irradiation on simple forms of behavior were
      studied using adult Tenebrio molitor mealworms. The beetles' motor behavior was
      studied in conditions of different motivations, i.e., positive (food) and
      negative (avoidance of light), in otherwise identical experimental conditions.
      The beetles had to navigate a defined space to reach their target - potato or
      cover from light. Experiments consisted of one trial per day for five days.
      Target attainment time was measured in groups of beetles. Behavior in both cases
      developed as follows: an initial orientation reaction appeared and was followed
      by adaptation to the apparatus. Exposure to weak electromagnetic irradiation led
      to increases in the response time at the initial stages of the experiments. The
      effects of irradiation were seasonal in nature and differed in the two types of
      behavior.

PMID- 20680477
TI  - Changes in neurons and gliocytes in the mesoaccumbocingulate system on perinatal
      exposure to morphine in rats.
AB  - Studies of changes in the numbers and some morphometric parameters of neurons and
      gliocytes in the mesoaccumbocingulate (MAC) dopaminergic system in rats were
      performed using pre- and postnatal exposure of this system to opiates, i.e., 0.1
      mg as 1% morphine hydrochloride solution into the amnion of fetuses of female
      Wistar rats (n = 4) on post-fertilization day 17 or i.p. to rat pups on postnatal
      day 4 (n = 4). Perinatal exposure to morphine induced chromophilic degeneration,
      swelling, and the death of some neurons, along with decreases in the volumes of
      other (less damaged) neurons in the MAC system of rats. Neuron damage, more
      marked after prenatal administration, was accompanied by an increase in the
      number of microgliocytes and their phagocytic activity. Morphine did not alter
      the number of satellite macrogliocytes or the mean distance from these cells to
      the bodies of less damaged neurons.

PMID- 20680478
TI  - Studies of histogenetic and neurodegenerative processes in the nervous system
      using heterotopic neurotransplantation.
AB  - The aim of the present article is to summarize our own experimental and published
      data on neurotransplantation into ectopic sites such as peripheral nerves
      (mainly) and the anterior chamber of the eye in rats. The review addresses
      questions touching on the following problems: the histogenesis and survival of
      nervous tissue after transplantation, the interaction between transplanted
      tissues with recipient tissues, assessment of long-term living transplants,
      simultaneous transplantation of different embryonic rudiments, transplantation of
      spinal cord ganglia, and the effects of trophic factors on the development of
      transplants. New data on stem cell transplantation into peripheral nerves are
      discussed.

PMID- 20680479
TI  - Chronic cannabinoid administration to periadolescent rats modulates the metabolic
      response to acute cocaine in the adult brain.
AB  - PURPOSE: To analyze brain metabolic response to acute cocaine in male and female
      Wistar rats with or without a history of cannabinoid exposure during
      periadolescence. PROCEDURES: The synthetic cannabinoid agonist CP 55,940 (CP) or
      its vehicle (VH), were administered to male and female rats during
      periadolescence. When these animals reached adulthood, saline and cocaine-induced
      changes in 2-deoxy-2-[18F]fluoro-D-: glucose (FDG) uptake were studied by
      positron emission tomography. RESULTS: The baseline (post-saline) metabolism in
      the septal nuclei was higher in CP-females than in VH-females, although septal
      metabolism was lower in CP-females after cocaine, reaching similar values to
      those of VH-females at baseline. Cocaine did not affect metabolism in VH-females.
      Periadolescent cannabinoid treatment did not influence baseline metabolism in
      males although cocaine reduced the FDG uptake in the dorsal striatum of males
      that received the VH but not CP. CONCLUSIONS: These results suggest that
      cannabinoids during periadolescence modify baseline and cocaine-evoked brain
      metabolism in a sex-dependent manner. In the case of CP-females, the involvement
      of septal metabolic alterations in their susceptibility to the rewarding effects
      of cocaine should be further investigated.

PMID- 20680480
TI  - Shortening the duration of [18F]FDG PET brain examination for diagnosis of brain
      glioma.
AB  - PURPOSE: Some patients cannot remain immobile for a long duration of 60 min,
      which is generally applied in the case of a 2-deoxy-2-[(18)F]fluoro-D-glucose
      ([(18)F]FDG) dynamic positron emission tomography (PET) scan. We investigated the
      change of the parametric values when the time duration of PET data was shortened.
      PROCEDURES: Eight normal subjects and four subjects with brain glioma were
      studied. The rate values of K(1), k(2), k(3), and K(i) parametric images were
      computed by changing the time duration from 20 to 60 min, and changes of those
      parametric values were compared. RESULTS: The change was 20-30% and 3-5% for k(3)
      and K(i), respectively, when the scan time was shortened from 60 to 40 min. The
      ratios of normal and disease regions in k(3) and K(i) values were similar, and
      contrasts of those images were not changed when the scan time was shortened to 40
      min. CONCLUSIONS: These results demonstrate that the short time duration of
      [(18)F]FDG PET examination can provide an acceptable estimation of parametric
      k(3) and K(i) images.

PMID- 20680481
TI  - Isoflurane anaesthesia differentially affects the amphetamine sensitivity of
      agonist and antagonist D2/D3 positron emission tomography radiotracers:
      implications for in vivo imaging of dopamine release.
AB  - PURPOSE: Using positron emission tomography in isoflurane-anaesthetised cat, we
      recently demonstrated that the effect of D-amphetamine (AMPH) was greater on the
      binding potential (BP(ND)) of the agonist dopamine D2/D3 radiotracer (+)-4
      [(11)C]propyl-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1, 4]oxazin-9-ol
      ([(11)C]-(+)-PHNO) than on that of the antagonist [(11)C]-raclopride, a finding
      that we were unable to replicate in conscious rat. Herein we tested whether
      isoflurane differentially affects the AMPH sensitivity of [(11)C]-(+)-PHNO and
      [(3)H]-raclopride. PROCEDURES: Conscious or isoflurane-anaesthetised rats
      pretreated intravenously (i.v.) with saline or 4 mg/kg AMPH were co-injected i.v.
      with [(11)C]-(+)-PHNO/[(3)H]-raclopride or [(3)H]-(+)-PHNO/[(11)C]-(-)-N-propyl
      norapomorphine ([(11)C]-(-)-NPA) and euthanised 2, 10, 20, 30, 40 or 60 min
      following [(11)C]-(+)-PHNO/[(3)H]-raclopride or 60 min following [(3)H]-(+)
      PHNO/[(11)C]-(-)-NPA. Striatal binding at 60 min, estimated by the specific
      binding ratio (SBR) and the binding potential with respect to non-displaceable
      binding (BP(ND)) for pseudodynamic data, was calculated using the simplified
      reference tissue model. RESULTS: Isoflurane increased [(11)C]-(+)-PHNO, [(3)H]
      (+)-PHNO and [(11)C]-(-)-NPA SBR (mean +/- SD) by 80 +/- 30%, 170 +/- 50% and 120
      +/- 40%, and doubled the effect of AMPH on the SBR of these radiotracers to -61
      +/- 9%, -69 +/- 12% and -60 +/- 12%, respectively. Neither effect was seen for
      [(3)H]-raclopride SBR. Similar results were observed for [(11)C]-(+)-PHNO and
      [(3)H]-raclopride BP(ND). CONCLUSIONS: Isoflurane differentially increases the
      binding and AMPH sensitivity of [(11)C]-(+)-PHNO and [(11)C]-(-)-NPA relative to
      [(3)H]-raclopride, suggesting that agonist radiotracers will prove no more
      effective for imaging dopaminergic activity in human than antagonist
      radiotracers.

PMID- 20680482
TI  - Sleep apnea syndrome in a young cosmopolite urban adult population: risk factors
      for disease severity.
AB  - PURPOSE: The purpose of this study is to investigate the risk factors for
      obstructive sleep apnea (OSA) in young patients from an urban European city with
      many migrants. METHODS: The medical data of 2,343 patients referred for
      polysomnography from January 2007 till September 2009 were retrospectively
      reviewed in order to identify patients younger than 40 years with OSA and assess
      their characteristics. RESULTS: One hundred twenty-one of the 2,093 patients (6%)
      referred for diagnostic polysomnography were younger than 40 years and had OSA.
      There were 17 women and 104 men. The race was Caucasian in 55% (67/121) and
      African in 42% (51/121). The median apnea-hypopnea index (AHI) was 39 in men and
      23 in women (p < 0.01), 30 in Caucasians and 39 in Africans (p = 0.03). BMI was
      positively correlated to the AHI (correlation of 0.19, p = 0.04). Multiple
      regression modeling showed that African origin (p = 0.01), current smoking (p =
      0.05), and neck circumference (p < 0.01) were predictors of AHI, independently of
      BMI, but not the presence of upper airway abnormalities (p = 0.75). Co
      morbidities were frequent (hypertension, 20%; diabetes, 13%;
      hypercholesterolemia, 27%; depression, 13%; reflux and gastric ulcer, 13%;
      hypothyroidism, 5%; asthma, 9%), and were related to BMI (p = 0.02), nocturnal
      desaturation time (p = 0.02), and African origin (p = 0.024). CONCLUSIONS: In
      patients aged <40 years and suffering from OSA, disease severity was associated
      with high BMI, large neck circumference, male sex, and African origin. After
      adjustment for BMI, African origin, tobacco use, and neck circumference remained
      predictors of high AHI. Neither upper airway abnormalities nor co-morbidities
      were found to be a risk factor for higher AHI in this group of young patients
      from a European city.

PMID- 20680483
TI  - Ankyrin repeat-rich membrane spanning/Kidins220 protein interacts with mammalian
      Septin 5.
AB  - Neurotrophin receptors utilize specific adaptor proteins to activate signaling
      pathways involved in various neuronal functions, such as neurite outgrowth and
      cytoskeletal remodeling. The Ankyrin-Repeat Rich Membrane Spanning (ARMS)/kinase
      D-interacting substrate-220 kDa (Kidins220) serves as a unique downstream adaptor
      protein of Trk receptor tyrosine kinases. To gain insight into the role of
      ARMS/Kidins220, a yeast two-hybrid screen of a rat dorsal root ganglion library
      was performed using the C-terminal region of ARMS/Kidins220 as bait. The screen
      identified a mammalian septin, Septin 5 (Sept5), as an interacting protein. Co
      immunoprecipitation using lysates from transiently transfected HEK-293 cells
      revealed the specific interaction between ARMS/Kidins220 and Sept5. Endogenous
      ARMS/Kidins220 and Sept5 proteins were colocalized in primary hippocampal neurons
      and were also predominantly expressed at the plasma membrane and in the tips of
      growing neurites in nerve growth factor-treated PC12 cells. Mapping of Sept5
      domains important for ARMS/Kidins220 binding revealed a highly conserved N
      terminal region of Sept5. The direct interaction between ARMS/Kidins220 and Sept5
      suggests a possible role of ARMS/Kidins220 as a functional link between
      neurotrophin receptors and septins to mediate neurotrophin-induced intracellular
      signaling events, such as neurite outgrowth and cytoskeletal remodeling.

PMID- 20680484
TI  - Engineering of flavonoid O-methyltransferase for a novel regioselectivity.
AB  - An O-methyltransferase isolated from poplar, POMT7, was identified as a flavone 7
      O-methyltransferase. In order to generate a mutant of POMT-7 having a novel
      regioselectivity, we conducted an error-prone polymerase chain reaction. More
      than 100 mutants were screened and one of the mutants (POMT-M1) Asp257Gly,
      methylated the 3-hydroxyl group of flavonols in addition to 7-hydrdoxyl group.
      The mutation changed asparagine residue at the position of 257 into glycine. The
      kinetic parameters showed that the wild type POMT7 was better activity toward
      kaempferol and quercetin than the POMT7-M1. Using E. coli transformant expressing
      POMT7-M1, 58 microM of 3, 7-O-dimethylquercetin and 70 microM of 3, 7-O
      dimethylkaempferol from 100 microM of corresponding substrate were synthesized
      successfully.

PMID- 20680485
TI  - N-terminal pI determines the solubility of a recombinant protein lacking an
      internal transmembrane-like domain in E. coli.
AB  - We examined whether the isoelectric point (pI) of the Nterminal region of the
      recombinant protein 7xMefp1 acts as a universal index for expression of the
      protein in soluble form in E. coli. Expression analysis of 7xMefp1 fused to
      various N-terminal sequences with pI values ranging from 2.73 to 13.35 yielded
      three pI range-specific curves (acidic, neutral, and alkaline curves at pI 2.73
      3.25, 4.61-9.58, and 9.90-13.35, respectively) for soluble expression (by
      facilitated diffusion) as a proportion of total protein. For neutral N-termini
      (pI 4.61-9.58), the total amount of rMefp1 expressed was minimally affected by
      DeltaG(RNA) for unfolding the mRNA secondary structure. The highly hydrophilic
      nature of longer N-terminal sequences with strongly acidic and alkaline pI values
      reduced the translation of rMefp1-encoding transcripts, thereby reducing the
      amount of soluble rMefp1 produced. After characterizing both feedback and non
      feedback regulation in the acidic, alkaline, and neutral pI ranges, we suggest
      that three different pI range-specific soluble expression curves exist for the
      recombinant protein, each defined by specific ranges of the leader sequence pI
      values.

PMID- 20680486
TI  - Control of TrkA-induced cell death by JNK activation and differential expression
      of TrkA upon DNA damage.
AB  - TrkA, a receptor for nerve growth factor, plays a crucial role in neuronal cell
      growth and differentiation. However, overactivation of TrkA signaling leads to
      cell death in various cell types. TrkA-mediated cell death shows some
      similarities to DNA damage-induced cell death. In this study, we examined how
      TrkA-induced cell death is regulated upon DNA damage. Cytoplasmic expression of
      TrkA protein was differentially modulated during the camptothecin-induced DNA
      damage response in TrkA-expressing U2OS cells. TrkA-induced cell death was
      synergistically increased by DNA damage, but it was blocked in the presence of
      the JNK inhibitor SP600125. Overexpression of a 54-kDa JNK isoform (JNK1alpha2)
      aggravated TrkA-induced cell death and was associated with TrkA functional
      activation. These results suggest that TrkA shares a functional connection with
      other mediators in the DNA damage response via JNK signaling.

PMID- 20680487
TI  - Characterization of SHORT-ROOT function in the Arabidopsis root vascular system.
AB  - Development of the vascular tissues is a dynamic process that integrates
      extrinsic and intrinsic factors to control vascular tissue formation throughout
      the plant life cycle. During vascular tissue formation in Arabidopsis roots,
      radial and longitudinal signals, including nuclear factors and plant hormones,
      control the developmental processes involved in the specification,
      differentiation, and maintenance of the correct cell types. SHR, a GRAS
      transcription factor, has been known to regulate the specification of the stem
      cell niche and ground tissue identity in the root meristem in a non-cell
      autonomous manner. However, the role of SHR in the root vasculature is relatively
      overlooked, despite localization of its mRNA and protein in the stele. Here, we
      investigated the role of SHR in the vascular system of the primary root using a
      reverse genetic approach and detailed phenotypic analysis. A novel, loss-of
      function null mutant, shr-6, was isolated in the Columbia background, and
      vascular patterning was characterized in detail. Our results reveal that shr
      mutants have developmental defects in both protophloem and protoxylem elements.
      Our study also suggests that SHR plays a central role in the root vascular system
      to control patterning processes, possibly regulated by longitudinal and radial
      signals.

PMID- 20680488
TI  - Inhibition of histone deacetylase 10 induces thioredoxin-interacting protein and
      causes accumulation of reactive oxygen species in SNU-620 human gastric cancer
      cells.
AB  - Histone deacetylase (HDAC)10, a novel class IIb histone deacetylase, is the most
      similar to HDAC6, since both contain a unique second catalytic domain. Unlike
      HDAC6, which is located in the cytoplasm, HDAC10 resides in both the nucleus and
      cytoplasm. The transcriptional targets of HDAC10 that are associated with HDAC10
      gene regulation have not been identified. In the present study, we found that
      knockdown of HDAC10 significantly increased the mRNA expression levels of
      thioredoxin-interacting protein (TXNIP) in SNU-620 human gastric cancer cells;
      whereas inhibition of HDAC1, HDAC2, and HDAC6 did not affect TXNIP expression.
      TXNIP is the endogenous inhibitor of thioredoxin (TRX), which acts as a cellular
      antioxidant. Real-time PCR and immunoblot analysis confirmed that inhibition of
      HDAC10 induced TXNIP expression. Compared to class I only HDAC inhibitors,
      inhibitors targeting both class I and II upregulated TXNIP, indicating that TXNIP
      is regulated by class II HDACs such as HDAC10. We further verified that
      inhibition of HDAC10 induced release of cytochrome c and activated apoptotic
      signaling molecules through accumulation of reactive oxygen species (ROS). Taken
      together, our results demonstrate that HDAC10 is involved in transcriptional
      downregulation of TXNIP, leading to altered ROS signaling in human gastric cancer
      cells. How TXNIP is preferentially regulated by HDAC10 needs further
      investigation.

PMID- 20680489
TI  - Two mutations in pab-1 encoding poly(A)-binding protein show similar defects in
      germline stem cell proliferation but different longevity in C. elegans.
AB  - Four new alleles, bn116, bn117, bn118, and bn119, on LG I were isolated in C.
      elegans with defects in germline stem cell proliferation. Using genetic mapping
      and snip-SNP mapping, bn116, bn117, bn118, and bn119 were located 5.0 cM, 1.3 cM,
      2.3 cM, and 5.0 cM, respectively, to the right of dpy-5 on LG I. Further, bn116
      and bn119 were grouped into the same complementation group by a complementation
      test. They are loss-of-function recessive alleles that produce homozygous sterile
      worms whose germ cells do not proliferate during larval development. However, the
      worms contained normal somatic gonadal structures including distal tip cells and
      gonadal sheath cells, suggesting that the defect in germline proliferation was
      not caused by the absence of somatic signaling. Although DAF-16 was localized to
      the nucleus in all four mutants, the life span was extended only in the three
      mutants except bn116. These results suggest that the defect in germline stem cell
      proliferation, the presence of normal somatic gonadal tissues, and DAF-16 nuclear
      translocation were sufficient for extending the lifespan of the bn117, bn118, and
      bn119 mutants, but not the bn116 mutant. Intriguingly, bn116 and bn119 were
      identified as two different mutations on the same gene, pab-1, which encodes a
      poly(A)-binding protein. Therefore, although the bn116 and bn119 mutations cause
      similar defects in germ cell proliferation, their effects on life span are
      different.

PMID- 20680490
TI  - Acute stress responsive RGS proteins in the mouse brain.
AB  - Regulator of G-protein signaling (RGS) proteins play an important role in G
      protein coupled receptor (GPCR) signaling and the activity of some GPCRs is
      modulated via RGS protein levels during stress response. The aim of this study
      was to investigate changes in RGS protein mRNA expressions in the mouse brain
      after 2h restraint stress. The mRNA level of 19 RGS proteins was analyzed using
      real-time PCR in six brain regions, which included the prefrontal cortex,
      amygdala, hippocampus, hypothalamus, striatum, and pituitary gland, from control
      and stressed mouse. We found that the level of mRNA of each RGS varied according
      to brain region and that two to eight RGS proteins exhibited changes in mRNA
      levels in each brain region by restraint stress. It was also revealed that RGS4
      protein amount was consistent with mRNA level, indicating RGS4 protein may have
      regulatory roles in the acute stress response.

PMID- 20680491
TI  - Proliferating neural progenitors in the developing CNS of zebrafish require
      Jagged2 and Jagged1b.
AB  - In the central nervous system (CNS), giving rise to the diversity and the
      complexity of neurons is the spatial and temporal differentiation of neural stem
      cells and/or neural precursors. Here, we investigated the role of Jagged-mediated
      Notch signaling in the maintenance and differentiation of progenitor cells during
      late neurogenesis by analyzing the expression patterns of zebrafish jagged
      homologues, and by injecting their morpholinos. Expression of both jagged2 and
      jagged1b mRNA in the CNS suggested that they might be involved in control of
      differentiating neural progenitors in which they are involved later in
      development. In Jagged2 and Jagged1b knock-down embryos, the overall rate of cell
      division dramatically decreased, and the ectopic VeMe neurons were generated. The
      results suggest that Jagged-Notch signaling plays a critical role in the
      maintenance of proliferating neural precursors, and that the generation of late
      born neurons, especially VeMe neurons, is regulated by the interplay between
      Jagged2 and Jagged1b.

PMID- 20680492
TI  - Targeted therapies for non-clear renal cell carcinoma.
AB  - The treatment of advanced and metastatic kidney cancer has been revolutionized by
      the development of targeted systemic therapies. Despite the growing number of
      available agents approved for use against clear cell renal cell carcinoma,
      patients with non-clear histologies, constituting approximately 1 in 4 cases of
      kidney cancer, have not received the same attention. The majority of clinical
      trials testing novel targeted therapies have excluded non-clear subtypes,
      providing limited therapeutic options for patients with these diagnoses and their
      oncologists. This review will focus on the use of targeted therapies against the
      non-clear histologic subtypes of renal cell carcinoma: papillary I and II,
      chromophobe, and collecting duct. The unique genetic and molecular profiles of
      each distinct non-clear kidney cancer subtype will be described, as these
      differences are integral to the development and effectiveness of the novel agents
      used to treat them. Trials focusing on non-clear kidney cancer, or those that
      treated clear cell tumors along with significant numbers of non-clear subtypes,
      will be discussed. The role of cytoreductive nephrectomy and the use of
      neoadjuvant and adjuvant targeted therapy will be reviewed. Lastly, areas of
      future research will be highlighted.

PMID- 20680494
TI  - Proper laboratory notebook practices: protecting your intellectual property.
AB  - A laboratory notebook contains a wealth of knowledge that can be critical for
      establishing evidence in support of intellectual property rights and for refuting
      claims of research misconduct. The proper type, organization, use, maintenance,
      and storage of laboratory notebooks should be a priority for everyone at research
      institutions. Failure to properly document research activities can lead to
      serious problems, including the loss of valuable patent rights. Consequences of
      improper laboratory notebook practices can be harsh; numerous examples are
      described in court cases and journal articles, indicating a need for research
      institutions to develop strict policies on the proper use and storage of research
      documentation.

PMID- 20680493
TI  - Rebalancing immune specificity and function in cancer by T-cell receptor gene
      therapy.
AB  - Adoptive immunotherapy with tumor-specific T lymphocytes has demonstrated
      clinical benefit in some cancers, particularly melanoma. Yet isolating and
      expanding tumor-specific cells from patients is challenging and there is limited
      ability to control T-cell affinity and response characteristics. T-cell receptor
      (TCR) gene therapy, in which T lymphocytes for immunotherapy are redirected using
      an introduced rearranged TCR, has emerged as an important alternative. Successful
      TCR gene therapy requires consideration of a number of issues, including TCR
      specificity and affinity, optimal gene therapy constructs, types of T cells
      administered, and the survival and activity of the modified cells. In this review
      we highlight the rationale for and experience with TCR gene therapy as well as
      new approaches to enhancing it.

PMID- 20680495
TI  - Acetabular orientation variability and symmetry based on CT scans of adults.
AB  - PURPOSE: Understanding acetabular orientation is important in many orthopaedic
      procedures. Acetabular orientation, usually described by anteversion and
      abduction angles, has uncertain measurement variability in adult patients. The
      goals of this study are threefold: (1) to describe a new method for computing
      patient-specific abduction/anteversion angles from a single CT study based on the
      identification of anatomical landmarks and acetabular rim points; (2) to quantify
      the inaccuracies associated with landmark selection in computing the acetabular
      angles; and (3) to quantify the variability and symmetry of acetabular
      orientation. METHODS: A total of 25 CT studies from adult patients scanned for
      non-orthopaedic indications were retrospectively reviewed. The patients were
      randomly selected from the hospital's database. Inclusion criteria were adults 20
      65 years of age. Acetabular landmark coordinates were identified by expert
      observers and tabulated in a spreadsheet. Two sets of calculations were done
      using the data: (1) computation of the abduction and anteversion for each
      patient, and (2) evaluation of the variability of measurements in the same
      individual by the same surgeon. The results were tabulated and summary statistics
      computed. RESULTS: This retrospective study showed that acetabular abduction and
      anteversion angles averaged 54 degrees and 17 degrees, respectively, in adults. A
      clinically significant intra-patient variability of >20 degrees was found. We
      also found that the right and left side rim plane orientation were significantly
      correlated, but were not always symmetric. CONCLUSION: A new method of computing
      patient-specific abduction and anteversion angles from a CT study of the anterior
      pelvic plane and the left and right acetabular rim planes was reliable and
      accurate. We found that the acetabular rim plane can be reliably and accurately
      computed from identified points on the rim. The novelty of this work is that
      angular measurements are performed between planes on a 3-D model rather than
      lines on 2-D projections, as was done in the past.

PMID- 20680496
TI  - MR imaging of atlantoaxial joint in early rheumatoid arthritis.
AB  - PURPOSE: This study was done to assess the involvement of the atlantoaxial joint
      in patients with early rheumatoid arthritis and evaluate the role of magnetic
      resonance (MR) imaging in depicting this early joint involvement. MATERIALS AND
      METHODS: Twenty patients (16 women and four men, mean age 55.0+/-12.9 years) with
      clinical and laboratory evidence of early rheumatoid arthritis (mean disease
      duration <12 months) were included in our study. MR imaging of the atlantoaxial
      joint was performed in all patients within 3 months from diagnosis. The MR
      features were correlated with clinical and biochemical variables. RESULTS: Five
      (25.0%) of the 20 patients exhibited enhancement of the periodontoid synovial
      spaces after gadolinium administration due to inflammatory synovitis. Compared
      with patients without cervical involvement, these five patients showed
      significantly higher values of erythrocyte sedimentation rate [median 77.0 mm/h
      (range 25th and 75th percentile 69.0-86.0) vs median 33.0 mm/h (range 25th and
      75th percentile: 9.2-52) (p=0.007)]; significantly higher C-reactive protein
      values [median 53.6 mg/l (range 25th and 75th percentile 21.9-81.9) vs median
      14.0 mg/l (range 25th and 75th percentile 0.8-20) (p=0.03)]; higher disease
      activity score [median 4.2 (range 25th and 75th percentile 3.9-5.4) vs median 3.2
      (range 25th and 75th percentile 2.8-3.8) (p=0.03)]. Four (80%) of these five
      patients presented anti-citrulline antibodies (anti-CCP) and rheumatoid factor at
      laboratory testing. The latter was positive in 12 of the 20 patients (66%), and
      anti-CCP were positive in 15 (83%). CONCLUSIONS: MR imaging showed an
      atlantoaxial inflammatory synovitis in 25% of patients with early rheumatoid
      arthritis. Our results indicate that patients with higher disease activity are
      likely to be at higher risk of presenting early involvement of the atlantoaxial
      joint. MR imaging of the cervical spine is an excellent tool for assessing the
      early manifestations of rheumatoid arthritis before any destructive changes
      occur. Therefore, MR imaging should be included in the diagnostic workup in order
      to provide reliable guidance for treatment choices.

PMID- 20680497
TI  - Effectiveness and safety of CEUS-guided haemostatic injection for blunt splenic
      trauma: an animal experiment.
AB  - The aim of this study was to investigate whether complications occur after
      haemostatic agents are injected into blunt splenic injuries. After undergoing
      ultrasound (US), contrast-enhanced US (CEUS) and contrast-enhanced computed
      tomography (CECT) examinations, dogs with grade III-IV injury received the
      minimally invasive therapy. After treatment, CEUS was performed to observe
      changes in the regions treated. In the immediate group, dogs underwent laparotomy
      30 min after treatment to observe the haemostatic effect. In the survival group,
      animals underwent CEUS and CECT examinations to observe the short-term healing
      outcome and complications at 3, 7, 14, and 21 days after the injection. After
      undergoing CEUS and CECT examinations, 12 dogs with grade III-IV injury received
      the minimally invasive therapy. Before injection, CEUS examinations showed
      anechoic and/or hypoechoic perfusion defects and active bleeding at the injury
      sites, and CECT showed traumatic lesions as low-density regions without
      enhancement. After treatment, CEUS demonstrated the disappearance of active
      bleeding, and hyperechoic spots emerged at the injury sites. Uneven density
      regions were displayed on CECT. Treated areas were covered by blood clots and
      glue membrane in the immediate-group animals. Three weeks later, CEUS showed a
      decrease of hyperechoic spots in the survival group, and the splenic parenchyma
      enhanced uniformly on CECT. Laparotomy showed that the greater omentum had moved
      upwards and partly covered the wound in four animals, and the injury sites had
      completely healed. Histopathological examination showed that fibrous connective
      tissue covered the splenic capsule and that the haemostatic glue had degraded. No
      complication occurred, such as delayed splenic haemorrhage, splenic abscesses,
      splenic pseudoaneurysms, intestinal obstruction or intestinal adhesions. CEUS
      guided haemostatic injection is not only effective in stopping active bleeding
      immediately, but it is also safe in that no complications occurred during the 3
      weeks of follow-up. This study indicates that CEUS-guided percutaneous injection
      may provide a safe, feasible and effective therapy for blunt splenic trauma.

PMID- 20680498
TI  - Endovascular treatment of femoropopliteal stenoses/occlusions with a SilverHawk
      directional atherectomy device: immediate results and 12-month follow-up.
AB  - PURPOSE: This paper reports our immediate and 12-month follow-up results in the
      treatment of arterial stenoses/occlusions of the femoropopliteal region with the
      use of the SilverHawk directional atherectomy device (EV3, USA). MATERIALS AND
      METHODS: In an 18-month period, we treated 18 patients (13 men, five women, age
      range 39-81 years) with the SilverHawk directional atherectomy device. Inclusion
      criteria were symptomatic femoropopliteal stenosis/insufficiency,
      nonresponsiveness to medical therapy, and Rutherford categories 3-5. Exclusion
      criteria were based on the preliminary colour Doppler ultrasound (US) assessment
      and were plaque with a calcified component >50% and inadequate upstream and/or
      downstream vascular bed. Patients with severe vascular impairment, classified as
      TransAtlantic Inter-Society Consensus (TASC) D, were also excluded. RESULTS: The
      procedure was successfully completed in all cases, with evident recanalisation
      and sufficient wall remodelling. No major complication was observed. At
      assessment immediately after the procedure and over the following days, an
      improvement in clinical symptoms and in the Rutherford scale was observed. Follow
      up at 2 and 12 months identified one case of distal reocclusion subsequently
      treated with amputation, and two cases of restenosis (primary patency 79%)
      successfully treated with a repeat procedure (secondary patency 96%).
      CONCLUSIONS: The SilverHawk directional atherectomy device proved to be an
      effective and safe tool in all our patients treated for femoropopliteal
      stenosis/occlusion, with a significant improvement in both imaging findings and
      clinical signs and symptoms.

PMID- 20680499
TI  - CT colonography before colonoscopy in subjects with positive faecal occult blood
      test. Preliminary experience.
AB  - PURPOSE: We report a preliminary evaluation of the performance of computed
      tomography colonography (CTC) systematically obtained before optical colonoscopy
      (OC) in subjects with positive faecal occult blood test (FOBT) within a
      population-based screening programme for colorectal cancer (CRC). MATERIALS AND
      METHODS: Seventy-nine subjects with positive FOBT from a regional screening
      programme were invited to perform same day CTC and OC. CTC was performed with
      standard bowel preparation. OC with segmental unblinding was the reference
      standard. A per-patient per-adenoma analysis was performed. RESULTS: Forty-nine
      of 79 subjects (62%) with positive FOBT adhered to the study and completed both
      examinations. Twenty-two (44.9%) of the 49 had a cancer or an adenoma >=6 mm. Per
      patient sensitivity, specificity, negative predictive value and positive
      predictive value for cancer or adenoma >=6 mm were 95.5% (95%CI:77.2%-99.9%),
      51.9% (95%CI:32.0%-71.3%), 93.3% (95%CI:68.1%-99.8%) and 61.8% (95%CI:43.6%
      77.8%). CONCLUSIONS: In the setting of a FOBT-based screening programme for CRC,
      CTC showed a high sensitivity, but relatively low specificity and positive
      predictive value, for cancer and adenoma >=6 mm. Probably performing CTC without
      faecal tagging as second line test after a positive FOBT is not a cost-effective
      strategy.

PMID- 20680500
TI  - Basilar artery thrombosis: imaging and endovascular therapy.
AB  - PURPOSE: Basilar artery thrombosis represents a rare type of ischaemic stroke
      with a mortality rate of 80%-90% if not promptly treated. The aim of our study
      was to review our experience with computed tomography angiography (CTA) in the
      diagnosis of basilar artery thrombosis and its treatment with endovascular
      procedures. MATERIALS AND METHODS: Our retrospective study is based upon 59
      nontrauma patients with episodes of sudden loss of consciousness. Patients were
      investigated using unenhanced brain CT followed by intracranial CTA (16-slice CT)
      when no parenchymal haemorrhage was detected. Patients with a CTA diagnosis of
      basilar artery thrombosis were considered for endovascular treatment. CTA
      accuracy was evaluated by considering the 12 patients who underwent endovascular
      angiography (the gold standard). The success of endovascular therapy was
      evaluated by considering the degree of microcirculatory reperfusion. RESULTS:
      After the exclusion of 33 patients affected by parenchymal or subarachnoid
      haemorrhage, the final study consisted of 26 patients who underwent CTA. Basilar
      artery thrombosis was diagnosed in 15 of them, and 12 were treated at our
      institution. The comparison between CTA and endovascular angiography showed 100%
      agreement in evaluating occlusion site and extension. Seven patients underwent
      intra-arterial lysis, and five underwent mechanical clot removal. CONCLUSIONS:
      CTA, with its wide availability and rapid execution times, is the most indicated
      examination in the case of suspected basilar artery thrombosis. Although there is
      a lack of randomised controlled prospective studies suggesting the most
      appropriate therapeutic approach to basilar artery thrombosis, our study lends
      weight to the role of interventional neuroradiology in the treatment of this
      condition.

PMID- 20680501
TI  - Role of magnetic resonance cholangiography in biliary complications of orthotopic
      liver transplantation.
AB  - PURPOSE: The aim of this study was to evaluate the role of magnetic resonance
      cholangiography (MRC) in the detection of biliary complications following
      orthotopic liver transplantation (OLT). MATERIALS AND METHODS: Seventy-eight
      transplant patients with clinically suspected biliary complications were
      evaluated with 1.5-T magnetic resonance imaging (MRI) using a surface coil. All
      patients were imaged with the following sequences: axial T1-weighted and axial
      and coronal T2-weighted, 2D spin echo (SE) breath-hold radial cholangiography,
      and coronal 3D single-shot turbo spin echo (SS-TSE) with respiratory triggering.
      Patients with negative MRI underwent clinical and sonographic followup. When
      biliary complications were present, diagnostic confirmation was obtained by
      endoscopic retrograde cholangiopancreatography (ERCP) (n=13), percutaneous
      transhepatic cholangiography (PTC) (n=20), ultrasonography (n=10) or computed
      tomography (CT) (n=2). In 11 cases, surgical confirmation was also obtained.
      RESULTS: MRC detected biliary complications in 44/78 patients, in particular, 42
      biliary strictures (37 anastomotic and five intrahepatic), 40 of which were
      confirmed by other imaging modalities. In 25/37 cases of anastomotic stricture,
      preanastomotic dilatation of the biliary tract was also demonstrated. Other MRC
      detected biliary complications were biliary sludge (n=4), biloma (n=5), and
      biliary stones (n=3). In four cases, PTC revealed biliary complications that had
      not been detected with MRC (false negative results). In two cases, MRC showed
      unconfirmed strictures of the intrahepatic ducts and biliodigestive anastomosis
      (false positive results). The sensitivity, specificity, positive (PPV) and
      negative (NPV) predictive values and diagnostic accuracy of MRC were 93.5%,
      94.4%, 96.7%, 89.5% and 93.9%, respectively. CONCLUSIONS: Our results confirm
      that MRC is a reliable technique for depicting biliary anastomoses and detecting
      biliary complications after OLT. The high diagnostic accuracy of MRC indicates
      that this examination should be routinely employed in all OLT patients with
      clinically suspected biliary complications.

PMID- 20680502
TI  - Underreported vertebral fractures in an Italian population: comparison of plain
      radiographs vs quantitative measurements.
AB  - PURPOSE: Vertebral fractures (VFs) are the hallmark of osteoporosis and are
      responsible for almost 70,000 hospital admissions yearly, implying social costs
      and impaired quality of life for patients. In recent years, several techniques,
      both qualitative and quantitative, have been proposed for VF diagnosis, but a
      gold standard is not yet available and the visual semiquantitative (VSQ)
      assessment proposed by Genant remains the most validated. However, given the lack
      of a standardised method, in clinical practice, the diagnosis of VF is often
      missed, and patients are not correctly assessed. The aim of our study was to
      estimate the percentage of VFs not detected in clinical practice in italian
      population using the VSQ method and a new morphometric technique. MATERIALS AND
      METHODS: In 283 postmenopausal women referred to our clinic for osteoporosis
      screening, we performed a clinical examination, plain spinal radiographs (for VSQ
      assessment) and digital computerised morphometry (DCM) to assess VFs. Bone
      density was measured using dual-energy X-ray absorptiometry (DXA). RESULTS: Forty
      seven percent of patients had a T score <-2.5 standard deviations (SD), and 35.2%
      were osteopenic, but no significant correlations between T score and grade or
      number of fractures were found. DCM identified VFs in 38.5% of patients versus
      32.5% using the VSQ method. Overall, 280 VFs were detected by DCM and 236 by VSQ,
      whereas only 105 were recognised by the reports. CONCLUSIONS: VFs went undetected
      in 55.5% according to the VSQ method on standard spinal radiographs. Therefore,
      the morphometric technique may be helpful when performed with the
      semiquantitative approach to improve recognition of VFs. However, other studies
      are needed to further validate the utility of this new morphometric technique in
      clinical practice.

PMID- 20680503
TI  - The role of receptor-interacting protein 140 in the accumulation of fat in
      ovariectomised rats.
AB  - BACKGROUND: Receptor-interacting protein 140 (RIP140) is a corepressor for
      nuclear receptors with an important role in the inhibition of energy expenditure.
      Postmenopausal women have increased white adipose tissue (WAT), and excessive
      accumulation of adipose tissue (obesity) implies a health risk. The aim of the
      present work was to investigate the time course of RIP140 expression in WAT
      during the development of ovariectomy (OVX)-induced obesity in rats. METHODS: OVX
      was performed in female Sprague-Dawley (SD) rats 8 weeks old. Body weight and
      food intake were determined once a week. WAT of sham-operated, OVX and OVX plus
      17beta-estradiol therapy (OVX/E2) female SD rats was weighed and used to analyse
      RIP140 and uncoupling protein 1 (UCP-1) expression by Western blot. RESULTS: Food
      intake and body weight were significantly increased during the 2-8 weeks after
      OVX. Even though body weight increased until killing, food intake progressively
      decreased from 9 to 16 weeks after OVX in rats. Meanwhile, increased WAT mass and
      decreased RIP140 expression in WAT were observed in OVX rats. In contrast, the
      expression of UCP-1, a key target gene of RIP140, in WAT of OVX rats was
      significantly higher than in sham-operated rats. All of these alterations caused
      by OVX were mostly reversed by the replacement of 17beta-estradiol. CONCLUSIONS:
      The down-regulation of RIP140 in WAT may play a compensatory role in OVX-induced
      obesity in rat.

PMID- 20680504
TI  - The importance of the length of the limbs for gastric bypass patients--an
      evidence-based review.
AB  - The ideal length of the gastric bypass limbs is debated. Recent evidence suggests
      that standard limb lengths used today have a limited impact on patient weight
      loss. Our objective was to appraise critically the available evidence on the
      influence of the length of gastric bypass limbs on weight loss outcomes. We
      systematically reviewed MEDLINE, the Cochrane database of evidence-based reviews,
      and the Database of Abstracts of Reviews of Effects for articles reporting the
      effect of gastric bypass length on outcomes published between 1987 and 2009. Four
      randomized controlled trials and several retrospective studies were identified
      and reviewed. Longer Roux limb lengths (at least 150 cm) were associated with a
      very modest weight loss advantage in the short term in superobese patients. No
      significant impact of alimentary limb length on weight loss for patients with
      body mass index (BMI) <50 was seen. When the length of the common channel
      approaches 100 cm, a significant impact on weight loss is observed. The currently
      available literature supports the notion that a longer Roux limb (at least 150
      cm) may be associated with a very modest weight loss advantage in the short term
      in superobese patients but has no significant impact on patients with BMI <=50.
      To achieve weight loss benefit due to malabsorption, bariatric surgeons should
      focus on the length of the common channel rather than the alimentary or
      biliopancreatic limbs when constructing a gastric bypass especially in the
      superobese population where failure rates after conventional gastric bypass are
      higher.

PMID- 20680505
TI  - Does pregnancy increase the need for revisional surgery after laparoscopic
      adjustable gastric banding?
AB  - BACKGROUND: Over 80% of laparoscopic adjustable gastric banding (LAGB) patients
      are women, and approximately half of these are of reproductive age; therefore,
      pregnancy post-LAGB is common. It is not known if pregnancy increases the need
      for revisional procedures. We compare the incidence of revisions in two matched
      cohorts of LAGB patients, with or without subsequent pregnancy. METHODS: From
      September 1994 to May 2009, 5,467 patients underwent LAGB at the Centre for
      Bariatric Surgery, Australia. Women with births post-LAGB were matched to
      controls, with a "matched follow-up date" calculated equivalent to pregnancy.
      Rates of primary and overall revisions for band-related (erosions and proximal
      pouch dilatations) and port/tubing complications were compared for cases and
      controls at 2 and 3 years post-pregnancy. RESULTS: One hundred eighty-nine women
      had >=1 pregnancies post-LAGB, including 137 with follow-up at 2 years and 104 at
      3 years post-pregnancy. There was no significant difference in band or
      port/tubing revisions between groups at either time point: 16.8% vs 10.5% (p =
      0.13) and 23.9% vs 14.6% (p = 0.09) for primary band revisions, and 5.8% vs 5.3%
      (p = 0.84) and 10.5% vs 6.6% (p = 0.35) for primary port/tubing revisions at 2
      and 3 years, respectively. Percentage excess weight loss (%EWL) 3 years post
      pregnancy was similar (47.9% vs 47.7%). Pregnancy LAGB management was not found
      to affect revisions; however, less time between LAGB and pregnancy was associated
      with a higher rate of primary band revisions (p = 0.03). CONCLUSION: These data
      suggest that pregnancy post-LAGB does not affect revision rate or %EWL; however,
      a shorter time between LAGB operation and pregnancy may predispose to band
      revisions.

PMID- 20680506
TI  - Effect of different bariatric operations on food tolerance and quality of eating.
AB  - Many bariatric operations are associated with reduced food tolerance and frequent
      vomiting, which may cause nutritional deficiencies and influence quality of life.
      However, the impact of different bariatric procedures on quality of eating and
      food tolerance has not yet been studied enough. Two hundred and eighteen
      participants filled a quality of eating questionnaire, at three different time
      periods after bariatric operation: short-term (3-6 months, n = 63), medium-term
      (6-12 months, n = 69) and long-term follow-up (over 12 months, n = 86). The
      participants underwent the following procedures: 99 patients have had Roux-en-Y
      gastric bypass (RYGB), 49 laparoscopic gastric banding (LAGB), 56 sleeve
      gastrectomy (SG), and 14 biliopancreatic diversion with duodenal switch (BPD-DS).
      At short-term period score achieved for all section of the questionnaire was
      similar for all operations. The total score of the questionnaire at the medium
      term group was 20.27 +/- 3.57, 14.47 +/- 5.92, 22.27 +/- 4.66, and 20.91 +/- 3.26
      (p < 0.001) and the total score for the long-term group of was 21.56 +/- 5.16,
      15.5 +/- 3.75, 20.45 +/- 4.9, and 24.2 +/- 2.16 (p < 0.001) for RYGB, LAGB, SG,
      and BPD-DS, respectively. In a linear regression model we found that LAGB
      patients had a significantly lower total score compared to all other procedures
      (p < 0.001). Every 1% of %EWL was associated with a total score decrease in 0.045
      points (p = 0.009). Impaired quality of eating and food intolerance is common
      following many types of bariatric procedures. However, the difficulties diminish
      as time passes after operation and can be affected by the type of procedure.
      Patients undergoing LAGB have significantly greater limitations and difficulties
      to ingest variety of foods.

PMID- 20680507
TI  - The suppressive effects of lanthanum on the production of inflammatory mediators
      in mice challenged by LPS.
AB  - Lanthanide ions have been proven to have various biologic effects. Lanthanum with
      extremely active physical and chemical property was evidenced to possess
      antibacterial and immune adjustment effects. In the present study, the anti
      inflammatory effects of lanthanum chloride (LaCl(3)) on lipopolysaccharide (LPS)
      challenged mice were examined in vivo and in vitro. The results indicated that
      LaCl(3) can greatly decrease the secretion of tumor necrosis factor alpha (TNF
      alpha) and interleukin (IL)-1beta as well as TNF-alpha mRNA expression in the
      mice challenged with LPS. To clarify the mechanism involved, the effects of
      LaCl(3) on the activation of nuclear factor (NF)-kappaB were examined both in
      liver and in peritoneal macrophages. The LPS-induced activation of NF-kappaB was
      significantly blocked by LaCl(3). These findings demonstrate that the inhibition
      of the LPS-induced inflammatory media, such as TNF-alpha and IL-1beta, by
      LaCl(3), is due to the inhibition of NF-kappa B activation.

PMID- 20680508
TI  - Effects of lead exposure on nitric oxide-associated gene expression in the
      olfactory bulb of mice.
AB  - Lead (Pb) is known to have toxic effects on the brain; however, data regarding
      its specific toxic effects on the olfactory bulb are lacking. Therefore, we
      investigated the relationship between acute Pb exposure and alterations in gene
      expression associated with the nitric oxide signaling pathway in the olfactory
      bulb of mice. After administration of Pb (intraperitoneal injections of 1 or 10
      mg/kg Pb(CH(3)CO(2))(2) . 3H(2)O once per day for 4 days), body weight, motor
      activity, and gene expression in the olfactory bulb of mice were examined. High
      doses of Pb resulted in significant decreases in body weight, but motor
      coordination was not significantly altered until 11 days after the end of Pb
      treatment. The expression patterns of dimethylarginine dimethylaminohydrolase 1
      (Ddah1), superoxide dismutase 1 (Sod1), and superoxide dismutase (Ccs) were
      increased, whereas expression of the Stratifin (Sfn) gene was significantly
      decreased following treatment with 10 mg/kg Pb. The expression patterns of nitric
      oxide synthases at the mRNA and protein levels, however, were not significantly
      altered by treatment with 10 mg/kg Pb. These findings indicate that Pb-induced
      neurotoxicity may be modulated in part by the expression of Ddah1, Sod1, Ccs, and
      Sfn in the olfactory bulb.

PMID- 20680509
TI  - Development and validation of an anodic stripping voltammetric method for
      determination of Zn(2+) ions in brain microdialysate samples.
AB  - An easy, rapid, and sensitive anodic stripping voltammetric method with a
      controlled growth mercury drop electrode has been developed and validated for the
      determination of Zn(2+) ions in brain microdialysate samples obtained from rats.
      The considered level of the zinc concentration in the dialysate was 0.5-6 ppb. In
      the investigated method, the stripping step was carried out by using a
      differential pulse potential-time voltammetric excitation signal. The optimal
      experimental conditions as well as the instrumental and accumulation parameters
      and supporting electrolyte composition were investigated. The optimized method
      was validated for precision, linearity, and accuracy. Mean recovery 82-110% was
      achieved, the precision expressed by CV not greater than 7.6% and the linearity
      given by correlation coefficient not lower than 0.9988. The limit of detection
      was 0.1 ppb. No interferences were observed. Due to high linearity, precision,
      and sensitivity, the developed method may be successfully applied in the
      determination of zinc ions in microdialysate brain samples. The results obtained
      for the first time demonstrate detailed characteristics of the determination of
      zinc in the brain microdialysate fluid by the ASV method. It may be applied in a
      wide range of physiological and pharmacological studies which focus on very low
      zinc concentration/alteration in various compartments of the organisms.

PMID- 20680511
TI  - Effect of cerium on photosynthetic pigments and photochemical reaction activity
      in soybean seedling under ultraviolet-B radiation stress.
AB  - Effects of cerium (Ce) on photosynthetic pigments and photochemical reaction
      activity in soybean (Glycine max L.) under ultraviolet-B (UV-B) radiation stress
      were studied under laboratory conditions. UV-B radiation caused the decrease in
      chlorophyll content, net photosynthetic rate, Hill reaction activity,
      photophosphorylation rate and Mg(2+)-ATPase activity. Ce (III) (20 mg L(-1))
      could alleviate UV-B-induced inhibition to these photosynthetic parameters
      because values of these photosynthetic parameters in Ce (III) + UV-B treatment
      were obviously higher than those with UV-B treatment alone. Dynamic changes of
      the above photosynthetic parameters show that Ce (III) could slow down the
      decrease rate of these photosynthetic parameters during a 5-day UV-B radiation
      and quicken the restoration during recovery period. The final restoration degree
      of five parameters mentioned above in leaves exposed to low level of UV-B
      radiation (0.15 W m(2)) was higher than that exposed to high level (0.45 W m(2)).
      Correlating net photosynthetic rate with other four parameters, we found that the
      regulating mechanisms Ce (PiIota) on photosynthesis under various level of UV-B
      radiation were not the same. The protective effects of Ce (III) on photosynthesis
      in plants were influenced by the intensity of UV-B radiation.

PMID- 20680510
TI  - Effects of acute in vivo cisplatin and selenium treatment on hematological and
      oxidative stress parameters in red blood cells of rats.
AB  - Although cisplatin (cisPt) is one of the most often used cytotoxic drugs in the
      treatment of cancer, its clinical application is associated with nephrotoxicity
      and a cumulative anemia. In this study, we evaluated posible protective effects
      of selenium (Se) on hematological and oxidative stress parameters in rats,
      acutely treated with cisPt. Four groups of Wistar albino rats included control
      rats, cisPt-treated (7.5 mg/kg of body weight of cisPt, i.p.), Se-treated (6
      mg/kg of body weight of Na(2)SeO(4), i.p.), and Se and cisPt co-treated rats. The
      rats were killed 72 h after treatment; hematological and oxidative stress
      parameters were followed in red blood cells. The results showed depletion in
      platelet number induced by high acute doses of cisPt and strong utilization of
      reduced glutathione, resulting in elevation of GSSG/2 GSH ratio. Se treatment was
      followed by stimulated erythropoiesis, increased lipid peroxidation, and GSH
      depletion. Se and cisPt co-treatment were followed by stimulated erythropoiesis
      and significant recovery of reduced glutathione status when compared with cisPt
      treated rats. In conclusion, acute doses of Se and cisPt primarily act as pro
      oxidants. CisPt influenced antioxidative properties of exogenous Se and their
      synergistic effects may partially participate in protection against cisPt-induced
      toxicity.

PMID- 20680512
TI  - Effect of selenium supplementation on lipid peroxidation, antioxidant enzymes,
      and lactate levels in rats immediately after acute swimming exercise.
AB  - The present study aims to evaluate the effect of selenium supplementation on
      lipid peroxidation and lactate levels in rats subjected to acute swimming
      exercise. Thirty-two adult male rats of Sprague-Dawley type were divided into
      four groups. Group 1, control; group 2, selenium-supplemented; group 3, swimming
      control; group 4, selenium-supplemented swimming group. The animals in groups 2
      and 4 were supplemented with (i.p.) 6 mg/kg/day sodium selenite for 4 weeks. The
      blood samples taken from the animals by decapitation method were analyzed in
      terms of erythrocyte-reduced glutathione (GSH), serum glutathione peroxidase
      (GPx) and superoxide dismutase (SOD), and plasma malondialdehyde (MDA) and
      lactate using the colorimetric method, and serum selenium values using an atomic
      emission device. In the study, the highest MDA and lactate values were found in
      group 3, while the highest GSH, GPx and SOD values were obtained in group 4 (p <
      0,001). Group 2 had the highest and group 3 had the lowest selenium levels (p <
      0,001). Results of the study indicate that the increase in free radical
      production and lactate levels due to acute swimming exercise in rats might be
      offset by selenium supplementation. Selenium supplementation may be important in
      that it supports the antioxidant system in physical activity.

PMID- 20680513
TI  - Gold in human semen around and away from a gold deposit area.
AB  - The study included evaluation of semen from normal, healthy adults and estimation
      of gold in seminal plasma from two regions Nilambur valley (Malappuram District,
      Kerala Province, India; n = 11), where gold deposit is present and Kollam town
      (Kerala Province, India; n = 13) where gold is not present in soil. All samples
      showed normal spermiogram. Gold was estimated in seminal plasma by employing
      inductively coupled plasma emission spectrophotometry. It varied from 0.23-1.15
      ppm with mean 0.68 ppm in study area while in control area it was 0.13-0.71 ppm
      with a mean of 0.41 ppm. Statistical studies (independent 't' test) showed
      significantly high level (p < 0.05) of gold in seminal plasma from study area.
      ANOVA test proved that gold in seminal plasma is a significant (p < 0.05) factor
      for total spermatozoa count and its percentage of motility.

PMID- 20680514
TI  - Galanthamine and related alkaloids production by Leucojum aestivum L. shoot
      culture using a temporary immersion technology.
AB  - The process of galanthamine and related alkaloids production by Leucojum aestivum
      shoot culture in a temporary immersion system was studied. It was established
      that temporary immersion approach is prospective for development of a
      biosynthetic process for obtaining valuable Amaryllidaceae alkaloids. Both
      immersion frequency and temperature had significant effect on biomass
      accumulation and the yields of galanthamine and related alkaloids. The maximal
      yield of galanthamine was achieved at the cultivation of L. aestivum shoot
      culture in temporary immersion RITA((r)) system at immersion frequency 15 min
      flooding and 8 h stand-by periods, at 26  degrees C. Data on the relationships in
      the biological system "Nutrient medium-L. aestivum shoot culture-galanthamine"
      are presented as well.

PMID- 20680515
TI  - An immunohistochemical study on the expressional dynamics of kisspeptin neurons
      relevant to GnRH neurons using a newly developed anti-kisspeptin antibody.
AB  - To investigate the reported discrepancy regarding the immunohistochemical
      expression of kisspeptin neurons, we produced a new antibody against synthetic
      peptide containing the same amino acid residual sequence as rat kisspeptin10.
      Although the antibody showed cross-reactivities against neurons other than
      kisspeptin neurons, these cross-reactivities were excluded by preabsorption with
      neuropeptide FF (NPFF). Immunohistochemistry using the antibody preabsorbed with
      NPFF showed specific kisspeptin immunoreactivities (IRs) in the arcuate nucleus
      (Arc), the inner layer of the median eminence, and the infundibulum in the rat
      hypothalamus. IRs were more intense in the adult female rats than in the males.
      This sexual dimorphism became observable at the 7th day after birth. These IRs
      intensified with age. Ovariectomy enhanced the IRs in the Arc in the female rats.
      In contrast, regarding IRs in the anteroventral periventricular nucleus (AVPV),
      only a few immunoreactive fibers were detected in the adult rats. We applied this
      antibody for the investigation of the interaction between kisspeptin fibers and
      gonadotropin-releasing hormone (GnRH) neurons. No direct morphological
      interaction between the cell bodies of GnRH neurons and kisspeptin fibers was
      observed in the medial preoptic area. Many projections of kisspeptin fibers were
      found close to the GnRH fibers in the lateral part of the median eminence.
      However, we did not observe any direct contact between kisspeptin fibers and the
      GnRH fibers. These results suggest that kisspeptin neurons regulate GnRH neurons
      not via the synaptic contact but via another information transmission process
      that is not synapse-dependent, such as volume transmission.

PMID- 20680516
TI  - Xenon enhances LPS-induced IL-1beta expression in microglia via the extracellular
      signal-regulated kinase 1/2 pathway.
AB  - The extracellular signal-regulated kinase (ERK) is involved in the cytokine
      production of immune cells. In this study, we show the influence of xenon on
      phosphatase activity, ERK 1/2 signalling and cytokine expression in microglia.
      The murine microglia cell line BV-2 was treated with 50 ng/ml lipopolysaccharide
      (LPS) and 74% xenon in 21% O(2) and 5% CO(2). Cytokine levels were examined by
      gene expression analysis, Western blot and enzyme-linked immunosorbent assay.
      Phosphatase inhibition was assessed with p-nitrophenylphosphate and
      phosphorylation of ERK 1/2 via Western blot. Xenon significantly enhanced LPS
      mediated IL-1beta expression. ERK 1/2 phosphorylation was observed after xenon or
      LPS treatment which was inhibited by the use of the MEK inhibitor U0126. Xenon
      and LPS in combination superimposed individual effects on ERK 1/2 activation.
      Xenon decreased cellular phosphatase activity in microglia by 20% and inhibited
      dephosphorylation of ERK 1/2 up to 1 h. The blocking of ERK 1/2 reduced IL-1beta
      expression in xenon and LPS-treated cells to a level obtained by LPS alone. In
      conclusion, xenon enhanced LPS-induced IL-1beta expression in microglia by
      activation of ERK 1/2 signalling. Xenon's interference with phosphatases may be a
      key feature to affect multiple intracellular signalling pathways.

PMID- 20680517
TI  - Sedation confounds outcome prediction in cardiac arrest survivors treated with
      hypothermia.
AB  - BACKGROUND: Therapeutic hypothermia is commonly used in comatose survivors' post
      cardiopulmonary resuscitation (CPR). It is unknown whether outcome predictors
      perform accurately after hypothermia treatment. METHODS: Post-CPR comatose
      survivors were prospectively enrolled. Six outcome predictors [pupillary and
      corneal reflexes, motor response to pain, and somatosensory-evoked potentials
      (SSEP) >72 h; status myoclonus, and serum neuron-specific enolase (NSE) levels
      <72 h] were systematically recorded. Poor outcome was defined as death or
      vegetative state at 3 months. Patients were considered "sedated" if they received
      any sedative drugs <= 12 h prior the 72 h neurological assessment. RESULTS: Of 85
      prospectively enrolled patients, 53 (62%) underwent hypothermia. Furthermore, 53
      of the 85 patients (62%) had a poor outcome. Baseline characteristics did not
      differ between the hypothermia and normothermia groups. Sedative drugs at 72 h
      were used in 62 (73%) patients overall, and more frequently in hypothermia than
      in normothermia patients: 83 versus 60% (P = 0.02). Status myoclonus <72 h,
      absent cortical responses by SSEPs >72 h, and absent pupillary reflexes >72 h
      predicted poor outcome with a 100% specificity both in hypothermia and
      normothermia patients. In contrast, absent corneal reflexes >72 h, motor response
      extensor or absent >72 h, and peak NSE >33 ng/ml <72 h predicted poor outcome
      with 100% specificity only in non-sedated patients, irrespective of prior
      treatment with hypothermia. CONCLUSIONS: Sedative medications are commonly used
      in proximity of the 72-h neurological examination in comatose CPR survivors and
      are an important prognostication confounder. Patients treated with hypothermia
      are more likely to receive sedation than those who are not treated with
      hypothermia.

PMID- 20680518
TI  - Treatment of acquired angioedema with icatibant: a case report.

PMID- 20680519
TI  - Clinical applications of bedside ultrasonography in internal and emergency
      medicine.
AB  - Ultrasonography (US) is an invaluable tool in the management of many types of
      patients in Internal Medicine and Emergency Departments, as it provides rapid,
      detailed information regarding abdominal organs and the cardiovascular system,
      and facilitates the assessment and safe drainage of pleural or intra-abdominal
      fluid and placement of central venous catheters. Bedside US is a common practice
      in Emergency Departments, Internal Medicine Departments and Intensive Care Units.
      US performed by clinicians is an excellent risk reducing tool, shortening the
      time to definitive therapy, and decreasing the rate of complications from blind
      invasive procedures. US can be performed at different levels of practice in
      Internal Medicine, according to the experience of ultrasound practitioners and
      equipment availability. In this review, the indications for bedside US that can
      be performed with basic or intermediate US training will be highlighted.

PMID- 20680520
TI  - The effect of human umbilical cord blood cells on survival and cytokine
      production by post-ischemic astrocytes in vitro.
AB  - Cerebral ischemia induces death of all neural cell types within the region
      affected by the loss of blood flow. We have shown that administering human
      umbilical cord blood cells after a middle cerebral artery occlusion in rats
      significantly reduces infarct size, presumably by rescuing cells within the
      penumbra. In this study we examined whether the cord blood cells enhanced
      astrocyte survival in an in vitro model of hypoxia with reduced glucose
      availability. Primary astrocyte cultures were incubated for 2 h in no oxygen (95%
      N, 5% CO(2)) and low glucose (1% compared to 4.5%) media. Cord blood mononuclear
      cells were added to half the cultures at the beginning of hypoxia. Astrocyte
      viability was determined using fluorescein diacetate/propidium iodide (FDA/PI)
      labeling and cytokine production by the astrocytes measured using ELISA. In some
      studies, T cells, B cells or monocytes/macrophages isolated from the cord blood
      mononuclear fraction with magnetic antibody cell sorting (MACS) were used instead
      to determine which cellular component of the cord blood mononuclear fraction was
      responsible for the observed effects. Co-culturing mononuclear cord blood cells
      with astrocytes during hypoxia stimulated production of IL-6 and IL-10 during
      hypoxia. The cord blood T cells decreased survival of the astrocytes after
      hypoxia but had no effect on the examined cytokines. Our data demonstrate that
      the tested cord blood fractions do not enhance astrocyte survival when delivered
      individually, suggesting there is either another cellular component that is
      neuroprotective or an interaction of all the cells is essential for protection.

PMID- 20680521
TI  - Presentation and outcomes of patients aged 30 years and younger with colorectal
      cancer: a 20-year retrospective review.
AB  - Age may influence the clinicopathological characteristics and outcome of
      colorectal cancer. The aim of this study is to retrospectively review the
      characteristics and outcomes of patients diagnosed at age 30 years and younger.
      All patients diagnosed with colorectal adenocarcinoma at age 30 years or younger,
      referred to the British Columbia Cancer Agency between 1985 and 2005, were
      identified. Abstracted data included demographics, presenting symptoms, risk
      factors, stage at presentation, treatment received and overall survival. Survival
      analysis was by the method of Kaplan-Meier. From 16,732 patients with colorectal
      cancer, 78 (0.47%) were younger than or equal to 30 years of age. Sufficient data
      were available for 62 patients. Twenty-three patients (37%) had a rectal primary,
      and 52% of colon primaries were proximal. Seventeen patients (27%) presented with
      metastatic disease. The stage distribution among the 45 patients with localized
      disease was stage I 9%, stage II 42% and stage III 49%. A positive family history
      was reported in 27% of patients. Pain and bleeding were the most common
      symptomatic presentations. Five-year overall survival was 44% in the entire
      cohort; 54% in stage I-III disease and 12% in stage IV disease. Very young
      patients with colorectal cancer represent<0.5% of all referred cases in British
      Columbia. The majority presented without a positive family history. The 5-year
      survival for patients in our young cohort with localized disease appears inferior
      to that expected, although 5-year survival among patients with stage IV disease
      was observed to be higher than expected.

PMID- 20680522
TI  - Down-regulation of miR-126 expression in colorectal cancer and its clinical
      significance.
AB  - MicroRNAs (miRNAs) are non-coding RNAs that regulate the expression of target
      mRNAs. Altered expression of specific miRNAs in several tumor types has been
      reported. However, the expression levels of miR-126 in colorectal cancers are
      unclear. In this study, we compared the expression of miR-126 between colorectal
      cancer tissues and non-tumor tissues. The expression levels of miR-126 in
      colorectal cancer tissues were significantly lower than those in non-tumor
      tissues, and miR-126 overexpression inhibited the growth of colorectal cancer
      cells. This new information may help to clarify the molecular mechanisms involved
      in colorectal carcinogenesis and to indicate that miR-126 may be a novel
      suppressive microRNA and help to differentiate between malignant and normal
      colorectal tissue.

PMID- 20680523
TI  - Epstein-Barr virus-related lymphoproliferative disorder induced by equine anti
      thymocyte globulin therapy.
AB  - Post-transplant lymphoproliferative disorder (PTLD) is generally caused by an
      uncontrolled B-cell proliferation induced by Epstein-Barr virus (EBV) in the
      setting of impaired EBV-specific T-cell immunity. PTLD has been described in
      allogeneic hematopoietic stem cell transplant (HSCT) and rarely in autologous
      HSCT. Anti-thymocyte globulin (ATG) is being increasingly utilized for acute
      rejection in organ transplantation, severe autoimmune diseases and aplastic
      anemia. Mainly, the use of rabbit ATG has been associated with PTLD, which is
      considered to be more immunosuppressive than equine ATG. The sole administration
      of equine ATG has rarely been associated with PTLD. Due to the increased use of
      these potent and novel immunosuppressive agents, it is paramount to be aware of
      these complications. We present a 55-year-old man with an autologous HSCT who
      presented with an unusual case of monoclonal plasmacytic PTLD. His
      lymphoproliferative disorder occurred 3 years after his HSCT and 1 month after
      the use of equine ATG administered for severe aplastic anemia. We review current
      concepts of EBV-PTLD, including risk factors, the potential for preemptive
      therapy and various management strategies.

PMID- 20680524
TI  - Pediatric islet autotransplantation: indication, technique, and outcome.
AB  - Chronic pancreatitis is a rare disease in childhood. However, when severe, a
      total pancreatectomy may be the only option to relieve pain and restore quality
      of life. An islet autotransplant performed at the time of pancreatectomy can
      prevent or minimize the postsurgical diabetes that would otherwise result from
      pancreatectomy alone. In this procedure, the resected pancreas is mechanically
      disrupted and enzymatically digested to separate the islets from the surrounding
      exocrine tissue, and the isolated islets are infused into the portal vein and
      engraft in the liver. Because patients are receiving their own tissue, no
      immunosuppression is required. Islet autotransplant is successful in two thirds
      of children-these patients are insulin independent or require little insulin to
      maintain euglycemia. Factors associated with a more successful outcome include a
      younger age at transplant (<13 years), more islets transplanted, and lack of
      prior surgical procedures on the pancreas (partial pancreatectomy or surgical
      drainage procedures).

PMID- 20680525
TI  - Virus infections and type 1 diabetes risk.
AB  - Common intestinal infections caused by human enteroviruses (HEVs) are considered
      major environmental factors predisposing to type 1 diabetes (T1D). In spite of
      the active research of the field, the HEV-induced pathogenetic processes are
      poorly understood. Recently, after the first documented report on HEV infections
      in the pancreatic islets of deceased T1D patients, several groups became
      interested in the issue and studied valuable human material, the autopsy
      pancreases of diabetic and/or autoantibody-positive patients for HEV infections.
      In this review, the data on HEV infections in human pancreatic islets are
      discussed with special reference to the methods used. Likewise, mechanisms that
      could increase viral access to the pancreas are reviewed and discussed.

PMID- 20680526
TI  - Novel targets for treatment of adult acute lymphocytic leukemia.
AB  - The treatment of acute lymphocytic leukemia (ALL) results in long-term disease
      free survival in only 30-40% of adults. Conventional chemotherapy is toxic and
      woefully ineffective. Therefore, novel agents are being investigated. Among these
      agents are monoclonal antibodies such as rituximab, epratuzumab, and alemtuzumab
      and targeted therapies such as tyrosine kinase inhibitors, mTOR inhibitors, and
      mitogen-activated protein kinase (MEK) inhibitors. This article discusses such
      novel targets for the treatment of ALL.

PMID- 20680527
TI  - Multivariate predictive model for dyslexia diagnosis.
AB  - Dyslexia is a specific disorder of language development that mainly affects
      reading. Etiological researches have led to multiple hypotheses which induced
      various diagnosis methods and rehabilitation treatments so that many different
      tests are used by practitioners to identify dyslexia symptoms. Our purpose is to
      determine a subset of the most efficient ones by integrating them into a
      multivariate predictive model. A set of screening tasks that are the most
      commonly used and representative of the different cognitive aspects of dyslexia
      was proposed to 78 children from elementary school (mean age = 9 years +/- 7
      months) exempt from identified reading difficulties and to 35 dyslexic children
      attending a specialized consultation for dyslexia. We proposed a multi-step
      procedure: within each category, we first selected the most representative tasks
      using principal component analysis and then we implemented logistic regression
      models on the preselected variables. Spelling and reading tasks were considered
      separately. The model with the best predictive performance includes eight
      variables from four categories of tasks and classifies correctly 94% of the
      children. The sensitivity (91%) and the specificity (95%) are both high. Forty
      minutes are necessary to complete the test.

PMID- 20680528
TI  - Is season of birth related to developmental dyslexia?
AB  - Different moderators/mediators of risk are involved in developmental dyslexia
      (DD), but data are inconsistent. We explored the prevalence of season of birth
      and its association with gender and age of school entry in an Italian sample of
      dyslexic children compared to an Italian normal control group. The clinical
      sample included 498 children (345 boys, mean age 10.3 +/- 2.1 years) with DD, the
      control sample 1,276 children (658 boys, mean age 10.8 +/- 2.2 years) from four
      elementary schools from the same urban area, and with the same socio-economic
      status level. A prevalence of birth in autumn was found among children with DD
      compared to controls (34% versus 24%, p < 0.0001). Children with DD were more
      frequently males (p < 0.0001) and had a lower mean age of school entry (p <
      0.0001). Regarding the distribution of ages, 11.4% of children with DD, but none
      of the subjects in the control group, started school before 5.7 years. Therefore,
      greater risk of DD was related to age of school entry (OR = 2.72), gender (OR =
      2.16), and season of birth (OR = 1.21). Significant interactions between boys
      with DD born in autumn, and correct school of entry (OR = 2.56) were joint
      predictors of higher risk of DD. The association between birth in autumn and DD
      may be explained by the earlier age of school entry, which may be a critical
      element in the youngest children with DD or at risk to DD. Whether Italian school
      policy is oriented to anticipate the school entry, a closer detection of early
      learning disorders and associated risk factors (familial load, specific language
      disorders, and attention deficit hyperactivity disorder) should be warranted.

PMID- 20680529
TI  - Osteoporosis in ankylosing spondylitis.
AB  - Osteoporosis (OP) is a frequent complication of ankylosing spondylitis (AS), even
      in early stages of the disease, and is associated with elevated levels of
      biochemical markers of bone turnover, proinflammatory cytokines, and acute-phase
      reactants. This suggests that systemic inflammatory mediators, such as
      interleukin-6 and tumor necrosis factor-alpha, may be involved. Various factors
      that conceivably work in conjunction with one another also cause bone loss in AS
      (eg, genetic polymorphisms of vitamin D, low levels of osteoprotegerin and sex
      steroid hormones, and impaired calcium and vitamin D absorption). Dual x-ray
      absorptiometry for assessing bone mineral density (BMD) has limitations in
      patients with AS because of unreliability of spinal measurements, particularly in
      advanced disease with new bone formation. Femoral neck BMD is reduced and
      correlates with increased risk of vertebral fractures. Hence, measurement of BMD
      at the femoral neck may provide the most accurate means of detecting osteopenia
      and OP and could assess fracture risk in AS patients. No guidelines are available
      for detection and treatment of OP in AS, and most patients are young men, who are
      less likely to be screened. The only evidence-based recommendation is that
      optimal control of disease activity in AS prevents bone loss. A recent study
      showed a beneficial effect of infliximab therapy on bone turnover markers and BMD
      in AS. Also, bisphosphonates may be useful in managing OP in AS.

PMID- 20680530
TI  - Hematopoietic stem cell transplantation for therapy-related myelodysplastic
      syndrome and acute leukemia: a single-center analysis of 47 patients.
AB  - The prognosis of therapy-related myelodysplastic syndrome and acute leukemia (t
      MDS/AL) remains poor. We retrospectively analyzed the data of 47 patients (31 AL
      and 16 MDS) who were treated at our institute. Thirty-three patients received
      disease-adapted chemotherapy, with a response rate of 73%, while 14 received no
      interventions due to an indolent course, such as MDS. The median follow-up of
      surviving patients was 1.9 years (range 0.1-10.5) after the diagnosis of t
      MDS/AL, and the estimated 3-year overall survival (OS) for all patients was 55%.
      Twenty-seven patients underwent allogeneic hematopoietic stem cell
      transplantation (HCT), and the 3-year non-relapse mortality was 17%. Twenty
      patients did not undergo HCT due to various reasons including advanced age or
      comorbidities. The 3-year OS was better in patients who received HCT than in
      those who did not (71 vs. 31%; p = 0.018). A multivariate analysis revealed that
      HCT was associated with a better OS. Although this study has several limitations,
      including a potential selection bias due to the retrospective nature of the
      analysis and a small number of patients, the results show that modern HCT may be
      useful for inducing long-term survival in a fraction of patients suffering from t
      MDS/AL. The present findings warrant future prospective studies.

PMID- 20680531
TI  - Reduced femoral component subsidence with improved impaction grafting at revision
      hip arthroplasty.
AB  - BACKGROUND: Despite stem subsidence being a major complication of femoral
      impaction bone grafting in cemented revision hip arthroplasty, few studies have
      distinguished subsidence at the prosthesis-cement interface from that at the
      cement-bone interface. It is unknown how technique developments intended to
      improve the procedure influence stability of the stem. QUESTIONS/PURPOSES: We
      used a sensitive technique to measure subsidence of a cemented polished
      collarless double-taper stem at each interface after femoral impaction grafting
      and compared subsidence, radiographic loosening, complications, and reoperations
      over three series of hips defined by technique developments. PATIENTS AND
      METHODS: Three series were defined: Series 1 (n = 23, irradiated allograft),
      Series 2 (n = 12, double-washed, size-profiled graft, nonirradiated bone, long
      stems as required), and Series 3 (n = 21, modular tamps). Stem subsidence was
      analyzed with Ein Bild Rontgen Analyse software. Radiographic loosening,
      complications, and reoperations were also determined. RESULTS: The median
      subsidence at 12 months for Series 1, 2, and 3 were 2.1, 0.5, and 0.7 mm at the
      prosthesis-cement interface and 1.3, 0.1, and 0.1 mm at the cement-bone
      interface. There were two postoperative Vancouver B periprosthetic fractures in
      Series 1, four hips were revised for loosening in Series 1, and there were no
      fractures or loosening in Series 2 and 3 at minimum 2 years' followup. There were
      no surviving hips radiographically classified as possibly or probably loose.
      CONCLUSIONS: Evolution in techniques of femoral impaction grafting in this study
      were associated with reduced subsidence of the stem at both the prosthesis-cement
      interface and cement-bone interface when compared to the original series.
      Concurrent with reduced stem subsidence was the absence of periprosthetic
      fracture, radiographic loosening, and complications requiring rerevision.

PMID- 20680532
TI  - Local recurrence, survival and function after total femur resection and
      megaprosthetic reconstruction for bone sarcomas.
AB  - BACKGROUND: The choices of treatment for patients with extensive tumors of the
      femur include total femur megaprosthesis or large allograft-prosthetic
      composites. Previous reports suggest variable survival ranging from 60-70% at 1
      to 2 years. However, these studies described earlier prostheses and techniques.
      QUESTIONS/PURPOSES: To confirm previous reports we determined (1) risk of local
      recurrence; (2) overall survivorship; and (3) function in patients with total
      femur reconstructions for tumors. METHODS: We retrospectively reviewed 23
      patients with total femur megaprostheses implanted between 1987 and 2006 after
      resection of bone tumors. Two patients lost at followup were excluded; the
      remaining 21 included 15 males and six females with a mean age of 21 years. The
      mean followup was 48 months (range, 1 month 17 years). Function was assessed
      according to the MSTS System II. RESULTS: No patient developed a local recurrence
      during followup. At last followup, six patients were continuously disease-free at
      a mean of 148 months, one patient had no evidence of disease after treatment of a
      recurrence, one patient was alive with disease, and 13 patients died of their
      disease at a mean time of 17 months. In 15 patients evaluated with the MSTS
      score, the mean score was 66%; four patients had over 75%, eight from 51% to 75%,
      three from 26% to 50%. Four patients (19%) had complications requiring further
      surgery in absence of trauma. A fifth patient had a posttraumatic periprosthetic
      fracture. CONCLUSIONS: A total femur prosthesis allows a limb-preserving
      procedure in tumors with extensive femoral involvement or in the presence of a
      skip lesion along the femur. The prognosis of these tumors is poor, but this
      reconstruction provides function with a relatively low rate of major
      complications.

PMID- 20680533
TI  - Warfarin therapy in patients with venous thromboembolism: patterns of use and
      predictors of clinical outcomes.
AB  - INTRODUCTION: Few studies have investigated current practices in the USA relating
      to warfarin use and monitoring, or the effects of warfarin discontinuation on
      risk of venous thromboembolism (VTE) and bleeding complications. This study
      investigated the effect of warfarin discontinuation on rates of VTE recurrence in
      a real-world setting. METHODS: Integrated Healthcare Information Services
      database records from January 2003 to September 2007 from patients aged at least
      18 years, hospitalized for VTE, and with at least two prescriptions or 60 days of
      warfarin treatment were reviewed, with warfarin discontinuation and international
      normalized ratio (INR) data collated. RESULTS: A total of 1027 of 8380 (12.3%)
      patients discontinued warfarin within 3 months. Overall, 1656 (19.8%) patients
      had no INR monitoring, with 38.1% of INR values being inside the therapeutic
      range (INR 2-3). Recurrent VTE was observed in 915 (10.9%) patients. Significant
      predictors of recurrent VTE (at any time) included discontinuation of warfarin
      within 3 months, time from index VTE to warfarin initiation, previous VTE-related
      hospitalization, and duration of index hospitalization. CONCLUSION: This study
      found that in a real-world population, less than 50% of warfarin patients
      achieved INR values within the therapeutic range. Warfarin discontinuation within
      3 months was associated with a higher rate of recurrent VTE.

PMID- 20680534
TI  - The patient-physician partnership in asthma: real-world observations associated
      with clinical and patient-reported outcomes.
AB  - INTRODUCTION: It is hypothesized that a good partnership between asthma patients
      and their physicians has a direct and positive influence on the patients'
      clinical and patient-reported outcomes. Conversely, poor partnership has a
      detrimental effect on clinical and patient-reported outcomes. This paper uses
      data from a real-world observational study to define partnership through matched
      physician and patient data and correlate the quality of partnership with observed
      clinical and patient-reported outcomes. METHODS: Data were drawn from Adelphi's
      Respiratory Disease Specific Programme, a cross-sectional study of consulting
      patients in five European countries undertaken between June and September 2009. A
      range of clinical and patient-reported outcomes were observed allowing analysis
      of the partnership between 2251 asthma patients and their physicians. RESULTS:
      Analysis demonstrates that the better the partnership between patient and
      physician, the more likely the patient is to have their asthma condition
      controlled (P<0.001), to experience fewer exacerbations (P<0.001), to have better
      quality of life (P<0.001), to have fewer sleep disturbances (P<0.001), and to
      have fewer patient-reported symptoms (P<0.001). Partnership is also associated
      with lower impact on lifestyle (P<0.01) and reduced days lost at work/school
      (P<0.05), and with patient satisfaction with their inhaler device (P<0.05).
      CONCLUSION: The patient-physician partnership is a contributory factor in the
      improvement of asthma treatment, and patient education may lead to improvement in
      a patient's ability to contribute to this. Device satisfaction is one of the
      markers of good partnership.

PMID- 20680535
TI  - Decarbonylated cyclophilin A Cpr1 protein protects Saccharomyces cerevisiae
      KNU5377Y when exposed to stress induced by menadione.
AB  - Cyclophilins are conserved cis-trans peptidyl-prolyl isomerase that are
      implicated in protein folding and function as molecular chaperones. The
      accumulation of Cpr1 protein to menadione in Saccharomyces cerevisiae KNU5377Y
      suggests a possibility that this protein may participate in the mechanism of
      stress tolerance. Stress response of S. cerevisiae KNU5377Y cpr1Delta mutant
      strain was investigated in the presence of menadione (MD). The growth ability of
      the strain was confirmed in an oxidant-supplemented medium, and a relationship
      was established between diminishing levels of cell rescue enzymes and MD
      sensitivity. The results demonstrate the significant effect of CPR1 disruption in
      the cellular growth rate, cell viability and morphology, and redox state in the
      presence of MD and suggest the possible role of Cpr1p in acquiring sensitivity to
      MD and its physiological role in cellular stress tolerance. The in vivo
      importance of Cpr1p for antioxidant-mediated reactive oxygen species (ROS)
      neutralization and chaperone-mediated protein folding was confirmed by analyzing
      the expression changes of a variety of cell rescue proteins in a CPR1-disrupted
      strain. The cpr1Delta to the exogenous MD showed reduced expression level of
      antioxidant enzymes, molecular chaperones, and metabolic enzymes such as
      nicotinamide adenine dinucleotide phosphate (NADPH)- or adenosine triphosphate
      (ATP)-generating systems. More importantly, it was shown that cpr1Delta mutant
      caused imbalance in the cellular redox homeostasis and increased ROS levels in
      the cytosol as well as mitochondria and elevated iron concentrations. As a result
      of excess ROS production, the cpr1Delta mutant provoked an increase in oxidative
      damage and a reduction in antioxidant activity and free radical scavenger
      ability. However, there was no difference in the stress responses between the
      wild-type and the cpr1Delta mutant strains derived from S. cerevisiae BY4741 as a
      control strain under the same stress. Unlike BY4741, KNU5377Y Cpr1 protein was
      decarbonylated during MD stress. Decarbonylation of Cpr1 protein in KNU5377Y
      strain seems to be caused by a rapid and efficient gene expression program via
      stress response factors Hsf1, Yap1, and Msn2. Hence, the decarbonylated Cpr1
      protein may be critical in cellular redox homeostasis and may be a potential
      chaperone to menadione.

PMID- 20680536
TI  - Heat shock protein 70 (Hsp70)-stimulated deoxycytidine deaminases from a human
      lymphoma cell but not the activation-induced cytidine deaminase (AID) from Ramos
      6.4 human Burkitt's lymphoma cells.
AB  - Deoxycytidine deaminase enzyme activity was reduced in lysates of human leukemic
      THP1 cells 24 h after transfection with siRNA designed to inhibit cell synthesis
      of heat shock protein 70 (Hsp70)1a and Hsp701b. The cytidine deaminase enzyme
      activity from the cell lysates was purified from an affinity column which
      contained bound single-stranded oligodeoxycytidylic acid. Deficient enzyme
      activity in certain elution fractions from the siRNA-transfected cells was
      restored by including recombinant HSP 70 in the assays. Enzyme activity in some
      other fractions was increased after siRNA transfection. Activation-induced
      cytidine deaminase (AID) is a central factor in the immune response. A more
      specific assay for AID was used to study the influence of Hsp70 on AID activity.
      Unlike Hsp70's ability to stimulate certain enzymes of DNA base excision repair
      and other cytidine deaminases, it had little effect on AID activity in vitro, or
      was weakly inhibitory.

PMID- 20680537
TI  - Distribution of CCND1 A870G polymorphism in patients with advanced uterine
      cervical carcinoma.
AB  - We examined the distribution of the CCND1 A870G (rs9344) polymorphic variant in
      patients with cervical cancer (n = 129) and healthy individuals (n = 288) in a
      sample of a Polish cohort. We showed that patients with advanced cervical cancer
      bearing the CCND1 A/A and A/G genotypes displayed a 1.811-fold increased risk of
      cervical cancer (95% CI = 1.150-2.852, p = 0.0098). We also found a significantly
      higher frequency of the CCND1 870A allele in patients with cancer than in
      controls, p = 0.0116. Our investigation confirmed that the CCND1 870A gene
      variant may be a genetic risk factor in the incidence of advanced cervical
      cancer.

PMID- 20680538
TI  - Aphasia and neglect are uncommon in cerebellar disease: negative findings in a
      prospective study in acute cerebellar stroke.
AB  - The aim of the present study was to examine if the most frequent cognitive
      disorders after cortical damage with a well-known cerebral lateralization, namely
      aphasia, neglect and extinction, are present in an unselected series of
      continuously admitted patients with acute cerebellar stroke. Twenty-two adults
      with acute cerebellar stroke were compared with 22 age- and education-matched
      healthy control subjects. High-resolution magnetic resonance images showed
      infarctions of the left cerebellar hemisphere in 12 and of the right hemisphere
      in ten patients. Standard aphasia tests revealed no statistically significant
      difference comparing patients with right- and left-sided ischemia and controls,
      whereas patients with left-sided ischemia showed mild deficits in a verb
      generation task. Neglect and extinction tasks revealed no significant differences
      between groups. Our findings support previous observations in the literature that
      cerebellar patients frequently perform within the normal range in standard
      neuropsychological tests. This does not exclude, however, that abnormalities may
      be present in more sophisticated testing of language and visuospatial functions.

PMID- 20680540
TI  - Pediatric ziprasidone ingestions.

PMID- 20680541
TI  - Glutathione system in young spontaneously hypertensive rats.
AB  - Glutathione (GSH) forms a part of the antioxidant system that plays a vital role
      in preventing oxidative stress, and an imbalance in the oxidant/antioxidant
      system has been linked to the pathogenesis of hypertension. The aim of this study
      was to investigate the status of the GSH system in the kidney of spontaneously
      hypertensive rats (SHR). Components of the GSH system, including glutathione
      peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST),
      and total GSH content, were measured in the kidneys of 4, 6, 8, 12, and 16 weeks
      old SHR and Wistar-Kyoto (WKY) rats. Systolic blood pressure of SHR was
      significantly higher from the age of 6 weeks onwards compared with age-matched
      WKY rats. GPx activity in the SHR was significantly lower from the age of 8 weeks
      onwards when compared to that in age-matched WKY rats. No significant differences
      were evident in the GPx-1 protein abundance, and its relative mRNA levels, GR,
      GST activity, and total GSH content between SHR and age-matched WKY rats. The
      lower GPx activity suggests of an impairment of the GSH system in the SHR, which
      might be due to an abnormality in its protein rather than non-availability of a
      cofactor. Its role in the development of hypertension in SHR however remains
      unclear.

PMID- 20680542
TI  - Succinate cytochrome c reductase in schistosomiasis: in vitro inhibition by some
      schistosomicidal drugs.
AB  - Enzymes in mitochondria play an important role in biological oxidation and energy
      production. To understand the effect of schistosomiasis on these important
      processes, succinate cytochrome c reductase (SCR) from control and Schistosoma
      infected mice was subjected for investigation. In this article, we report that
      SCR from Schistosoma-infected mouse showed a significant decrease in its Vmax and
      Km compared to control using both cytochrome c and 2,6-dichlorophenolindophenol
      as substrates. Furthermore, the kinetic studies of the purified SCR in the
      absence and presence of the schistosomicidal drugs praziquantel and Commiphora
      extract reveal that both drugs have an inhibitory action on the enzyme from the
      control and Schistosoma-infected mice and praziquantel changes the type of
      inhibition of SCR towards cytochrome c from mixed type in control to a
      competitive one in the case of the infection.

PMID- 20680539
TI  - Adaptation, expertise, and giftedness: towards an understanding of cortical,
      subcortical, and cerebellar network contributions.
AB  - Current cortico-centric models of cognition lack a cohesive neuroanatomic
      framework that sufficiently considers overlapping levels of function, from
      "pathological" through "normal" to "gifted" or exceptional ability. While most
      cognitive theories presume an evolutionary context, few actively consider the
      process of adaptation, including concepts of neurodevelopment. Further, the
      frequent co-occurrence of "gifted" and "pathological" function is difficult to
      explain from a cortico-centric point of view. This comprehensive review paper
      proposes a framework that includes the brain's vertical organization and
      considers "giftedness" from an evolutionary and neurodevelopmental vantage point.
      We begin by discussing the current cortico-centric model of cognition and its
      relationship to intelligence. We then review an integrated, dual-tiered model of
      cognition that better explains the process of adaptation by simultaneously
      allowing for both stimulus-based processing and higher-order cognitive control.
      We consider the role of the basal ganglia within this model, particularly in
      relation to reward circuitry and instrumental learning. We review the important
      role of white matter tracts in relation to speed of adaptation and development of
      behavioral mastery. We examine the cerebellum's critical role in behavioral
      refinement and in cognitive and behavioral automation, particularly in relation
      to expertise and giftedness. We conclude this integrated model of brain function
      by considering the savant syndrome, which we believe is best understood within
      the context of a dual-tiered model of cognition that allows for automaticity in
      adaptation as well as higher-order executive control.

PMID- 20680543
TI  - Bauhinia bauhinioides cruzipain inhibitor reduces endothelial proliferation and
      induces an increase of the intracellular Ca2+ concentration.
AB  - Proteinase inhibitors, isolated from different types of Bauhinia, have an effect
      on apoptosis, angiogenesis and inflammation. The Bauhinia bauhinioides cruzipain
      inhibitor (BbCI) is a Kunitz-type inhibitor and inactivates the cysteine
      proteinases cruzipain and cruzain from Trypanosoma cruzi. Cruzipain and tissue
      kallikrein have similar biochemical properties, e.g. the proteolytic cleavage of
      the kininogen precursor of lys-bradykinin. Tissue kallikrein stimulation in
      endothelial cells causes migration and capillary tube formation. The aim of this
      study was to examine whether the antiproliferative effect of BbCI is dependent on
      changes of the intracellular calcium concentration and membrane
      hyperpolarization. Endothelial cells were isolated from human umbilical cord
      veins (HUVEC). For proliferation experiments, HUVEC were incubated with BbCI (10
      100 MUmol/L) for 48 h. The proliferation was detected by cell counting with a
      Neubauer chamber. The effect of BbCI (10-100 MUM) on the membrane potential was
      measured with the fluorescence dye DiBAC4(3) and the effect on [Ca+2]i with the
      fluorescence probe Fluo-3 AM. The change of the fluorescence intensity was
      determined with a GENios plate reader (Tecan). The experiments showed that BbCI
      (10-100 MUmol/L) reduces the endothelial cell proliferation significantly in a
      concentration-dependent manner with a maximum effect at 100 MUmol/L (35.1+/-1.8%
      as compared to control (p<=0.05; n=45)). As compared to the control, the addition
      of BbCI (100 MUmol/L) caused a significant increase of systolic Ca2+ of 28.4+/
      5.0% after 30 min incubation. HUVEC treatment with BbCI (100 MUmol/L) showed a
      weak but significant decrease of the membrane potential of 9.5+/-0.9% as compared
      to control (p<=0.05; n=80). BbCI influenced significantly the endothelial
      proliferation, the intracellular Ca2+ concentration and the membrane potential.

PMID- 20680547
TI  - [Not Available].

PMID- 20680544
TI  - Hypoxia suppresses Kv 2.1 channel expression through endogenous 15
      hydroxyeicosatetraenoic acid in rat pulmonary artery.
AB  - We have previously reported that hypoxia activates lung 15-lipoxygenase (15-LOX),
      which catalyzes arachidonic acid to produce 15-HETE, leading to constriction of
      neonatal rabbit pulmonary arteries. Hypoxia suppresses Kv2.1 channel expression.
      Although the Kv channel inhibition by hypoxia is likely to be mediated through 15
      HETE, direct evidence is still lacking. To explore whether 15-LOX/15-HETE pathway
      contributes to the hypoxia-induced down-regulation of Kv2.1 channel, we performed
      studies using 15-LOX blockers, semi-quantitative PCR and western blot analysis.
      We found that Kv2.1 channel expression at the mRNA and protein levels was greatly
      up-regulated in pulmonary arterial smooth muscle cells (PASMCs) and pulmonary
      artery (PA) after blockade of endogenous 15-HETE under hypoxic condition. 15-HETE
      further decreased Kv2.1 channel expression in comparison with 12-HETE and 5-HETE
      in cultured PASMCs and PA under normoxic conditions. These data indicate that
      hypoxia suppresses Kv2.1 channel expression through endogenous 15-HETE in PA.

PMID- 20680548
TI  - History of the social sciences.

PMID- 20680549
TI  - "Discipline history" and "intellectual history" reflections on the historiography
      of the social sciences in Britain and France.

PMID- 20680550
TI  - [Not Available].

PMID- 20680551
TI  - [Not Available].

PMID- 20680552
TI  - [Not Available].

PMID- 20680553
TI  - [Not Available].

PMID- 20680554
TI  - [Not Available].

PMID- 20680556
TI  - [Not Available].

PMID- 20680555
TI  - [Not Available].

PMID- 20680557
TI  - [Not Available].

PMID- 20680558
TI  - Summaries of articles.

PMID- 20680559
TI  - Decreased competiveness of the foodborne pathogen Campylobacter jejuni during Co
      culture with the hyper-ammonia producing anaerobe Clostridium aminophilum.
AB  - Campylobacter spp. are a leading bacterial cause of human foodborne illness. When
      cocultured in anaerobic Bolton broth with the hyper-ammonia producing bacterium,
      Clostridium aminophilum, ammonia accumulation was greater and final growth of
      Campylobacter jejuni was reduced (CFU>or=1.4 log10/mL) compared to that obtained
      by pure culture controls. Co-culture with the less active ammonia-producing
      saccharolytic Prevotella albensis had no effect on final C. jejuni
      concentrations. When co-cultured similarly except with the addition of 10
      micromol/L monensin, monensin-susceptible Cl. aminophilum was reduced by 2 to 4
      log10 CFU/mL and concentrations of C. jejuni, which is insensitive to monensin,
      did not differ from its pure culture control. These results suggest that in the
      absence of added monensin, the hyper ammonia-producing Cl. aminophilum may be
      able to outcompete asaccharolytic C. jejuni for amino acid substrates and that
      this competitive ability was eliminated by addition on monensin.

PMID- 20680560
TI  - Mureinolytic ability of the rumen ciliate Diploplastron affine.
AB  - Rumen ciliate protozoa intensively engulf bacteria. However, their ability to
      utilize murein which is the main polysaccharide of bacterial cell wall has hardly
      been recognized. The present study concerns the ability of the rumen protozoa
      Diploplastron affine to digest and ferment murein. The ciliates were isolated
      from the rumen fluid and grown in vitro or inoculated into the rumen of
      defaunated sheep. The results of long-term cultivation of protozoa showed a
      positive correlation between their number and murein content in the culture
      medium. It was also found that bacteria-free D. affine ciliates incubated with or
      without murein produced volatile fatty acids at the rate of 12.3 and 8.7 pmol/h
      per protozoan, respectively, acetic, butyric and propionic acids being the three
      main acids released to the medium. Enzyme studies performed with the use of
      protozoan cell extract prepared from bacteria-free ciliates degraded murein at a
      rate of 25 U/mg protein per h; two mureinolytic enzymes were identified by
      zymographic technique in the examined preparation.

PMID- 20680561
TI  - Lactate dehydrogenase gene variability among predominant lactate utilizing
      ruminal bacteria.
AB  - The inter- and intraspecies variability of lactate dehydrogenase (ldh) gene was
      determined among the predominant ruminal lactate utilizing bacteria. Nearly
      complete nucleotide sequences of ldh gene, encoding NAD-dependent lactate
      dehydrogenase of three Megasphaera elsdenii and six Selenomonas ruminantium
      strains, were obtained and compared. Phylogenetic analyses revealed a limited
      variability between the ldh sequences studied. The majority of differences
      observed were silent mutations at the 3rd position of codons. Surprisingly, the
      intraspecies diversity of the ldh gene among S. ruminantium isolates was higher
      than the interspecies level between S. ruminantium and M. elsdenii, which
      strongly suggests the possibility of acquisition of this gene by horizontal gene
      transfer.

PMID- 20680562
TI  - Diversity of anaerobic fungi within cow manure determined by ITS1 analysis.
AB  - The diversity of anaerobic fungi was evaluated in cow semiliquid manure obtained
      from input homogenizing tank of biogas plant. Among three sets of tested primers,
      the combination of fungal universal ITS1F and Neocallimastigales specific Neo
      QPCR Rev primers was selected and used for the construction of clone library.
      Eighty-four new complete internal transcribed spacers (ITS1) and partial 5.8S
      rDNA sequences generated within this study were analyzed by Bayesian inference
      and assigned to an existing order of the Neocallimastigales. Sixty-seven% of
      sequences were affiliated with Cyllamyces, 24% with Piromyces, 7% with
      Anaeromyces, only 2% with Neocallimastix, and no sequences with Orpinomyces.
      According to Bayesian analysis the genus Caecomyces was polyphyletic and
      disappeared from the presented ITSbased phylogram. This study gave a first
      insight into the diversity of anaerobic fungi in cow manure, where the prevalence
      of fungi with bulbous morphology was indicated.

PMID- 20680563
TI  - Naturally occurring prebiotic oligosaccharides in poultry feed mixtures.
AB  - The presence of raffinose series oligosaccharides (RSO) was determined by an
      enzymic method in three commercially available chicken feed mixtures. All feed
      mixtures contained RSO at a concentration of 2.1-2.2%. Soya meal was identified
      as the exclusive source of RSO. Subsequently, the bifidogenic effect of stachyose
      (main soya bean RSO) was also assigned on the growth of poultry intestinal
      bifidobacteria. Bifidobacteria were counted in chicken intestinal tract using
      cultivation and FISH methods. Four out of 6 bifidobacterial strains tested grew
      significantly better on stachyose than on glucose. It can be thus concluded that
      chicken feed mixtures naturally contain prebiotic oligosaccharides in the form of
      RSO in higher levels (>2%) compared with the concentration (usually up to 1%)
      recommended for artificially added prebiotics. Our results therefore indicate
      that there is no reason for the supplementation of chicken feed mixtures with
      prebiotics with bifidogenic properties.

PMID- 20680564
TI  - Fructanolytic and saccharolytic enzymes of the rumen bacterium Pseudobutyrivibrio
      ruminis strain 3--preliminary study.
AB  - P. ruminis strain 3 was isolated from the ovine rumen and identified on the basis
      of comparison of its 16S rRNA gene with GenBank. The bacterium was able to grow
      on Timothy grass fructan, inulin, sucrose, fructose and glucose as a sole carbon
      source, reaching absorbance of population in a range of 0.4-1.2. During 1 d the
      bacteria exhausted 92-97% of initial dose of saccharides except for inulin (its
      utilization did not exceed 33%). The bacterial cell extract catalyzed the
      degradation of Timothy grass fructan, inulin and sucrose in relation to carbon
      source present in growth medium. Molecular filtration on Sephadex G-150,
      polyacrylamide gel electrophoresis combined with zymography technique and TLC was
      used to identify enzymes responsible for the digestion of sucrose and both
      polymers of fructose. Two specific endolevanases (EC 3.2.1.65), nonspecific beta
      fructofuranosidase (EC 3.2.1.80 and/or EC 3.2.1.26) and sucrose phosphorylase (EC
      2.4.1.7) were detected in cell-free extract from bacteria grown on Timothy grass
      fructan.

PMID- 20680565
TI  - Antibiotic resistance in commensal intestinal microflora.
AB  - The susceptibility toward antibiotics was determined by disc and MIC methods in
      Lactobacillus and, for comparison, in Escherichia coli strains isolated from
      cloacal swabs of broiler chickens derived from various farms in Slovakia. The
      occurrence of acquired tetracycline resistance in E. coli and lactobacilli
      isolated from the same sample was similar. The presence of tet(M), tet(S), tet(L)
      and ermB genes was demonstrated in lactobacilli while the tet(M) gene was not
      detected in E. coli.

PMID- 20680566
TI  - The presence of bifidobacteria in social insects, fish and reptiles.
AB  - The occurrence and species distribution of bifidobacteria in the digestive tract
      of important representatives of social insects such as ants, bees, wasps and
      bumblebees as well as the incidence of bifidobacteria in fecal samples of several
      species of vertebrates represented mainly by reptiles was assigned by culture
      independent method based on DGGE and real time PCR. Bifidobacteria were present
      in the gut of most social insects--honey bees, wasps, cockroaches and bumblebees,
      except for ants. In honey bees, where the counts of bifidobacteria ranged from 2
      to 8% of the total bacteria, the most common species seemed to be Bifidobacterium
      indicum. Proportion of bifidobacteria was found in broad range from 0.1 to 35-37%
      in wasps and cockroaches; the variance of bifidobacteria in bumblebees was lower,
      ranging from 1 to 7% of total bacterial count. Among studied vertebrates, the
      detectable presence of bifidobacteria was found only in trout (1.1%) and geckos
      (0.2%), but large amount of these bacteria was observed in Vietnamese box turtle,
      where bifidobacteria represented nearly one-fourth (22%) of total bacterial
      counts.

PMID- 20680567
TI  - Development of flow cytometry technique for detection of thinning of
      peptidoglycan layer as a result of solvent production by Clostridium
      pasteurianum.
AB  - Clostridium pasteurianum forms acetic and butyric acids in an initial growth
      phase, which is a typical feature of clostridial acetone-butanol fermentation
      where an initial accumulation of acids is followed by production of solvents 1
      butanol, acetone and ethanol. The initiation of the solvent production coupled
      with endospore formation leads to decrease of cell-wall thickness; thinner cell
      wall is more resistant against solvents and dyes. These changes can be observed
      by the method based on adaptation of Gram staining. The cell wall of G+ bacteria
      allows the entry of hexidium iodide and rhodamine 123, whereas the outer membrane
      of G- bacteria does not allow the uptake and therefore G+ bacteria are stained
      with higher fluorescence intensity than G- bacteria. The ratio of fluorescence
      intensity (FI) to forward scatter (FSC) was determined to correspond to G+
      bacteria when clostridia were producing less solvents. The significant drop of
      the ratio FI to FSC to the level corresponding to G- bacteria is detected after
      initiation of solvent production.

PMID- 20680568
TI  - PCR-DGGE analysis of bacterial population attached to the bovine rumen wall.
AB  - We isolated and amplified by PCR 16S rDNA from bacteria attached to the bovine
      rumen wall and analyzed it by denaturing gradient gel electrophoresis (DGGE) with
      subsequent sequence analysis. The attached bacterial community differed from the
      bacteria of rumen content; however, no differences were observed among the five
      epithelial sampling sites taken from each animal. The DGGE profile of the
      bacterial population attached to the rumen wall represented a high inter-animal
      variation.

PMID- 20680569
TI  - The ability of the rumen protozoan Eudiplodinium maggii to utilize chitin.
AB  - The ability was determined of the rumen ciliate Eudiplodinium maggii to utilize
      chitin from fungal cell wall. Cultivation experiments shoved that the population
      concentration (number of ciliates in vitro) was positively correlated with chitin
      doses. Cell extract prepared from the bacteria-free ciliates degraded colloidal
      chitin releasing 2.0 micromol reducing sugar per mg protein per h. End products
      of this reaction were chitotriose and N-acetylglucosamine. Incubation of the
      bacteria-free ciliates with chitin resulted in an increase in the concentration
      of acetic, propionic and butyric acids in the incubation medium. The production
      rate of total volatile fatty acids (VFA) by ciliates incubated with and without
      chitin was 45.0 and 30.5 pmol VFA per protozoan, respectively, the molar
      proportion of particular acids remaining unchanged.

PMID- 20680570
TI  - PCR-DGGE-based study of fecal microbial stability during the long-term chitosan
      supplementation of humans.
AB  - A feeding study was performed to monitor the effect of chitosan intake on the
      fecal microbiota of ten healthy human subjects. Diversity of microflora was
      monitored during 8 weeks including 4 weeks of chitosan supplementations. Using
      denaturing gradient gel electrophoresis (DGGE) analysis of 16S rRNA gene
      amplicons and quantitative PCR method we revealed possible changes originating in
      the overall bacterial composition and also in the subpopulation of
      Bifidobacterium group. DGGE profiles displayed high complexity and individuality
      for each subject. Considerable variations in the composition of band patterns
      were observed among different persons. A raised level of fecal Bacteroides in
      response to chitosan intake was found in all samples. Bifidobacterium levels
      following chitosan intake increased or remain unchanged. Non-significant increase
      was, surprisingly, found in the numbers of butyrate-producing bacteria.

PMID- 20680571
TI  - Effects of 3-hydroxy-3-methylglutaryl-coenzyme a reductase inhibitor pravastatin
      on membrane lipids and membrane associated functions of Methanothermobacter
      thermautotrophicus.
AB  - The role of archaeal membrane and its lipid constituents was investigated in
      bioenergetic functions of Methanothermobacter thermautotrophicus. The effects
      were determined of the 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor,
      pravastatin, on lipid composition, and its impact on some bioenergetic functions
      of treated cells. Pravastatin remarkably inhibited the growth of M.
      thermautotrophicus. On membrane level, pravastatin treatment modulated the
      composition of the mixture of squalene and hydrosqualene derivatives as well as
      the activities of ATPase, A1Ao-ATP synthase and Na+/H+ antiporter. SDS-PAGE of
      chloroform-methanol extracts of membranes from control and pravastatin-treated
      cells revealed changes in the amount of AtpK proteolipids, which suggests that
      pravastatin modifies cell-membrane composition, hereby modulating the properties
      of some membrane-bound enzymes participating in energy transformation in
      methanoarchaea.

PMID- 20680572
TI  - Xylanases of anaerobic fungus Anaeromyces mucronatus.
AB  - The anaerobic fungus Anaeromyces mucronatus KF8 grown in batch culture on M10
      medium with rumen fluid and microcrystalline cellulose as carbon source produced
      a broad range of enzymes requisite for degradation of plant structural and
      storage saccharides including cellulase, endoglucanase, xylanase, alpha
      xylosidase, beta-xylosidase, alpha-glucosidase, beta-glucosidase, beta
      galactosidase, mannosidase, cellobiohydrolase, amylase, laminarinase, pectinase
      and pectate lyase. These enzymes were detected in both the intra- and
      extracellular fractions, but production into the medium was prevalent with the
      exception of intracellular beta-xylosidase, chitinases, N-acetylglucosaminidase,
      and lipase. Xylanase activity was predominant among the polysaccharide
      hydrolases. Extracellular production of xylanase was stimulated by the presence
      of cellobiose and oat spelt xylan. Zymogram of xylanases of strain KF8 grown on
      different carbon sources revealed several isoforms of xylanases with approximate
      molar masses ranging from 26 to 130 kDa.

PMID- 20680573
TI  - Improved protocol for high-quality co-extraction of DNA and RNA from rumen
      digesta.
AB  - We report an improved method for total nucleic acids extraction from rumen
      content samples. The method employs bead beating, and phenol-chloroform
      extraction followed by saline-alcohol precipitation. Total nucleic acids and RNA
      yield and purity were assessed by spectrophotometric measurements; RNA integrity
      was estimated using Agilent RNA 6000 Nano Kit on an Agilent 2100 Bioanalyzer. The
      method provided total nucleic acids and RNA extracts of good quantity and
      quality. The extraction is not time consuming and it is valuable for ecological
      studies of rumen microbial community structure and gene expression.

PMID- 20680574
TI  - Development of gut microflora in obese and lean rats.
AB  - The influence was evaluated of post-weaning normal nutrition and over-nutrition
      upon the development of the intestinal microbiota, the alkaline phosphatase
      activity (AP) and occurrence of obesity in male Sprague-Dawley rats (from days 21
      to 40 the control rats were submitted to ad libitum intake of a standard
      laboratory diet whereas overfed rats received the same diet supplemented with
      milk-based high fat liquid diet). The jejunal numbers of two dominant divisions
      of bacteria, i.e. Firmicutes (Lactobacillus/ Enterococcus--LAB) and the
      Bacteroidetes (Bacteroides/Prevotella--BAC), were determined using the
      fluorescent in situ hybridization (FISH) method, and the jejunal AP activity was
      assayed histochemically. On day 40, the overfed rats in comparison with control
      animals displayed increased adiposity accompanied by enhanced AP activity,
      abundance of LAB, lower amounts of BAC and, thereafter, higher LAB/BAC ratio
      (L/B). The numbers of LAB and L/B index positively correlated with body fat,
      energy intake and AP activity, whereas numbers of BAC showed an opposite
      tendency. These results revealed the significance of nutritional imprint upon the
      post-weaning development of intestinal microbial and functional axis and
      contribute to better understanding of their involvement in energy-balance control
      and in adverse and/or positive regulation of adiposity.

PMID- 20680575
TI  - Variability of treponemes in the rumen of ruminants.
AB  - Complete 16S rRNA sequences were determined of recently proposed new species of
      treponemes designated strain S and T. Sequence comparison indicated that both
      species belong to the Treponema saccharophilum cluster, having thus at least 5
      cultivable representatives. Phylogenetic analysis of available GenBank 16S rRNA
      sequences revealed two phylogenetically distant treponema clusters (T.
      saccharophilum cluster and T. bryantii cluster). Surprisingly, while among
      cultivated treponemes dominate T. saccharophilum cluster members, detailed
      analysis showed that all treponema-like sequences obtained by culture independent
      16S rRNA methods belong to the T. bryantii cluster, from which only two
      cultivable representatives have so far been known. Meta-analysis of available
      data revealed that treponemes are an infrequent and minor group of bacteria,
      representing less than 2.4% of total rumen bacteria.

PMID- 20680576
TI  - The antimicrobial action of low-molar-mass chitosan, chitosan derivatives and
      chitooligosaccharides on bifidobacteria.
AB  - The crude fractions of chitooligosaccharides (COS) and low-molar-mass chitosans
      (LMWC) were prepared by enzyme hydrolysis of chitosan (CS). Specific growth rate
      of B. adolescentis, B. bifidum, B. breve, B. catenulatum, B. infantis and B.
      longum ssp. longum was determined in the presence of 0.025 and 0.5 % COS (<5
      kDa), LMWC (5-10 kDa), and 0.025, 0.1 and 0.5% of CS, chitosan succinate and
      chitosan glutamate in vitro. Minimum inhibitory concentrations (MIC; assayed by
      colony counting on TPY agar plates) of COS-LMWC and CS ranged from 0.025% to
      0.75% of CS-LMWC. The growth of all bifidobacterial strains in the presence of
      chitosan, its derivatives and LMWC decreased at a concentration of 0.025%; the
      bacterial growth was completely inhibited at a concentration of 0.5%. COS did not
      show any inhibitory effect, an increased growth rate was even observed in the
      case of B. bifidum, B. catenulatum and B. infantis.

PMID- 20680577
TI  - Phosphorolytic cleavage of sucrose by sucrose-grown ruminal bacterium
      Pseudobutyrivibrio ruminis strain k3.
AB  - Rumen bacterium Pseudobutyrivibrio ruminis strain k3 utilized over 90% sucrose
      added to the growth medium as a sole carbon source. Zymographic studies of the
      bacterial cell extract revealed the presence of a single enzyme involved in
      sucrose digestion. Thin layer chromatography showed fructose and glucose-1
      phosphate (Glc1P) as end products of the digestion of sucrose by identified
      enzyme. The activity of the enzyme depended on the presence of inorganic
      phosphate and was the highest at the concentration of phosphate 56 mmol/L. The
      enzyme was identified as the sucrose phosphorylase (EC 2.4.1.7) of molar mass
      approximately 54 kDa and maximum activity at pH 6.0 and 45 degrees C. The
      calculated Michaelis constant (Km) for Glc1P formation and release of fructose by
      partially purified enzyme were 4.4 and 8.56 mmol/L while the maximum velocities
      of the reaction (Vlim) were 1.19 and 0.64 micromol/L per mg protein per min,
      respectively.

PMID- 20680578
TI  - Extracellular complex of chitinolytic enzymes of Clostridium paraputrificum
      strain J4 separated by membrane ultrafiltration.
AB  - Membrane diafiltration was used for separation of the extracellular complex of
      chitinolytic enzymes of C. paraputrificum J4 free from contaminants with molar
      mass higher than 100 kDa and lower than 30 kDa. The enzyme complex containing
      beta-N-acetylglucosaminidase (NAGase) and six endochitinases was concentrated on
      a membrane with cut-off 30 kDa. In this retentate, the NAGase/endochitinase
      specific activity was 13.5/6.5-times higher than in the initial culture filtrate.
      The proportion (in%) of endochitinases: 23 (90 kDa), 42 (86 kDa), 8 (72 kDa), 16
      (68 kDa) and 8 (60 kDa) was calculated from their peak areas (determined by
      densitometry) in images of zymograms. NAGase (38 kDa) was less active and stable
      at pH lower than 4 and higher than 8 but it was more temperature-stable than
      endochitinases, especially at 40-60 degrees C. In contrast to endochitinases, the
      pH optimum of NAGase activity was shifted by ca. 0.7 pH units to the alkaline
      region. Extracellular NAGase together with six endochitinases secreted by C.
      paraputrificum J4 were separated by membrane diafiltration and characterized by
      molar mass, stability and activity in dependence on pH and temperature. The
      knowledge of composition of chitinolytic enzymes, their pH and temperature
      stability is useful for optimization of the separation process.

PMID- 20680579
TI  - Survival of bifidobacteria administered to calves.
AB  - Twenty-five bifidobacteria were isolated from feces of calves. Isolates were
      identified, and their functional properties and antimicrobial activity were
      determined. From 10 strains with suitable properties rifampicin-resistant mutants
      (RRBs) were prepared and mixture of RRBs was administered to 2-d-old calves.
      These strains were identified by sequencing as Bifidobacterium animalis ssp.
      animalis (6 strains), B. thermophilum (2 strains), B. choerinum (1 strain) and B.
      longum ssp. suis (1 strain). The control group was without probiotic treatment.
      Survival ability of administered bifidobacteria was monitored in fecal samples by
      cultivation on modified TPY agar supplemented with mupirocin, acetic acid, and
      rifampicin. Administered bifidobacteria survived in gastrointestinal tract of
      calves for at least 60 d. Other bacteria were also determined after cultivation
      using fluorescence in situ hybridization (FISH). Bifidobacteria and lactobacilli
      dominated in fecal microflora. Significantly lower amounts of E. coli and higher
      amounts of bifidobacteria and total anaerobes were found in the treated group
      relative to the control group.

PMID- 20680580
TI  - Artificial tripartite symbiosis involving a green alga (Chlamydomonas), a
      bacterium (Azotobacter) and a fungus (Alternaria): morphological and
      physiological characterization.
AB  - A long-living artificial tripartite symbiosis involving a green alga
      (Chlamydomonas), a bacterium (Azotobacter) and a fungus (Alternaria) was
      established on carbon- and nitrogen-free medium. The basis of the interdependence
      is the complementation of photosynthetic CO2 assimilation and atmospheric
      nitrogen fixation. Green color of the colonies indicated that the algal cells had
      enough nitrogen to synthesize chlorophylls. The chlorophyll content was nearly
      40% of the control cells. The relatively high rate of photosynthetic oxygen
      evolution proved that nitrogen was effectively used for building up a well
      functioning photosynthetic apparatus. This was supported by the analysis of
      photosystems and ultrastructural investigations. In comparison with degreened
      algae cultured on nitrogen-free medium, the chloroplasts in the symbiont algal
      cells contained a well-developed, stacked thylakoid membrane system without
      extreme starch or lipid accumulation. The occurrence of the fungus in the
      association greatly increased the chlorophyll content. Far fewer types of amino
      acids were excreted by the tripartite cultures than by pure cultures.
      Cystathionine, which is a common intermediate in the sulfur-containing amino acid
      metabolism, was produced in high quantities by the tripartite symbiosis. This can
      mostly be attributed to the activity of the fungus.

PMID- 20680581
TI  - Microbial products from probiotic bacteria inhibit Salmonella enteritidis 857
      induced IL-8 synthesis in Caco-2 cells.
AB  - Oral administration of Lactobacillus spp. as probiotics is gaining importance in
      the treatment of intestinal inflammations. However, their mechanism of action is
      unknown. We investigated whether nonspecific binding Lactobacillus casei Shirota
      (LcS) and mannose-specific Lactobacillus plantarum 299v (Lp) and their spent
      culture supernatant (SCS) affect Salmonella enteritidis 857 (Se) growth, IL-8 and
      Hsp70 syntheses. In one set of experiments human enterocyte-like Caco-2 cells
      were infected with LcS, Lp or Se at 1-500 bacteria per cell for 1 h. In another
      set, cells were exposed to Se (0-200 per cell, 1 h) after exposure to
      lactobacilli (LB) (500 per cell, 30 min) or by co-incubation of Se and LB (1 h).
      The third set of experiments involved exposure of cells for 1 h to SCS or Se (100
      per cell) pretreated (1 h) in SCS. The effect of LB SCS on Se growth was
      evaluated by agar plate diffusion test. IL-8 and Hsp70 were assessed over 2-24 h
      using ELISA and Western blotting, respectively. Neither LcS nor Lp affected the
      Se growth and IL-8 production. In addition, they did not induce Hsp70 expression
      by Caco-2 cells. Instead, their SCS inhibited the Se growth and IL-8 production
      and induced the expression of Hsp70 by both crypt- and villus-like cells. The
      beneficial effect of Lactobacillus spp. to the intestinal inflammations might be
      associated with a decrease in IL-8 levels. This effect could be mediated, at
      least in part, via a secreted antimicrobial product(s) either directly against
      the pathogens or indirectly through the synthesis of Hsp70.

PMID- 20680582
TI  - Imaging mass spectrometry: viewing the future.
AB  - Imaging mass spectrometry (IMS) technology is an effective tool that is able to
      assess complex molecular mixtures in cells, tissues, or other sample types with
      high chemical specificity, allowing concurrent analysis of a variety of molecular
      species in a wide mass range, from small metabolites to large macromolecules such
      as proteins. Simultaneous localization of molecules, detection of post
      translational modifications, and relative quantitative information can be
      obtained in a single experiment. Images generated by MS are unique because they
      are derived from direct molecular measurements and do not rely on target-specific
      reagents such as antibodies. Thus, the ability to map spatial distributions
      coupled with the mass accuracy and chemical specificity for MS-based detection
      makes IMS an effective discovery tool. Further structural assessment of
      compounds, including MS/MS fragmentation analysis, can be utilized in an imaging
      experiment to achieve accurate molecular identifications.

PMID- 20680583
TI  - A mass spectrometry primer for mass spectrometry imaging.
AB  - Mass spectrometry imaging (MSI), a rapidly growing subfield of chemical imaging,
      employs mass spectrometry (MS) technologies to create single- and multi
      dimensional localization maps for a variety of atoms and molecules. Complimentary
      to other imaging approaches, MSI provides high chemical specificity and broad
      analyte coverage. This powerful analytical toolset is capable of measuring the
      distribution of many classes of inorganics, metabolites, proteins, and
      pharmaceuticals in chemically and structurally complex biological specimens in
      vivo, in vitro, and in situ. The MSI approaches highlighted in this Methods in
      Molecular Biology volume provide flexibility of detection, characterization, and
      identification of multiple known and unknown analytes. The goal of this chapter
      is to introduce investigators who may be unfamiliar with MS to the basic
      principles of the mass spectrometric approaches as used in MSI. In addition to
      guidelines for choosing the most suitable MSI method for specific investigations,
      cross-references are provided to the chapters in this volume that describe the
      appropriate experimental protocols.

PMID- 20680584
TI  - Imaging of metals, metalloids, and non-metals by laser ablation inductively
      coupled plasma mass spectrometry (LA-ICP-MS) in biological tissues.
AB  - The determination of the localization and distribution of essential and
      beneficial metals (e.g., Cu, Fe, Zn, Mn, Co, Ti, Al, Ca, K, Na, Cr and others),
      toxic metals (like Cd, Pb, Hg, U), metalloids (e.g., As, Se, Sb), and non-metals
      (such as C, S, P, Cl, I) in biological tissues is a challenging task for life
      science studies. Over the past few years, the development and application of mass
      spectrometric imaging (MSI) techniques for elements has been rapidly growing in
      the life sciences in order to investigate the uptake and the transport of both
      essential and toxic metals in plant and animal sections. Laser ablation
      inductively coupled plasma mass spectrometry (LA-ICP-MS) is a very sensitive and
      efficient trace, surface, and isotopic analytical technique for biological
      samples. LA-ICP-MS is increasingly utilized as an elemental mass spectrometric
      technique using double-focusing sector field (LA-ICP-SFMS) or quadrupole mass
      spectrometers (LA-ICP-QMS) to produce images of detailed regionally specific
      element distributions in thin biological tissue sections. Nowadays, MSI studies
      focus on brain research for studying neurodegenerative diseases such as
      Alzheimer's or Parkinson's, stroke, or tumor growth, or for the imaging of cancer
      biomarkers in tissue sections.The combination of the mass spectrometry imaging of
      metals by LA-ICP-MS with proteomics using biomolecular mass spectrometry (such as
      MALDI-MS or ESI-MS) to identify metal-containing proteins has become an important
      strategy in the life sciences. Besides the quantitative imaging of metals, non
      metals and metalloids in biological tissues, LA-ICP-MS has been utilized for
      imaging metal-containing proteins in a 2D gel after electrophoretic separation of
      proteins. Recent progress in applying LA-ICP-MS in life science studies will be
      reviewed including the imaging of thin slices of biological tissue and
      applications in proteome analysis in combination with MALDI/ESI-MS to analyze
      metal-containing proteins.

PMID- 20680585
TI  - Lipid detection, identification, and imaging single cells with SIMS.
AB  - Time-of-flight secondary ion mass spectrometry (ToF-SIMS) can be utilized to map
      the distribution of various molecules on a surface with submicrometer resolution.
      Many of its biological applications have been in the study of membrane lipids,
      such as phospholipids and cholesterol. For these studies, the effectiveness of
      chemical mapping is limited by low signal intensity from various biomolecules.
      Because of the high-energy nature of the SIMS ionization process, many molecules
      are identified by detection of characteristic fragments. Cluster ion sources are
      able to increase ionization, leading to increased information collected from a
      surface. In this chapter, we highlight the utility of SIMS to image lipids at
      single cells. Particularly, we will describe sample preparation, data collection,
      and the analysis of lipids for two systems; rat oligodendrocytes and Tetrahymena
      thermophila. SIMS spectra yield information regarding lipid identity and
      concentration across cell surface.

PMID- 20680586
TI  - The application and potential of ion mobility mass spectrometry in imaging MS
      with a focus on lipids.
AB  - Tissue profiling and imaging by MALDI mass spectrometry has allowed the direct
      analysis and localization of biomolecules in tissue. However, due to the in situ
      nature of this technique, the complexity of tissue, and the need for a chemical
      matrix in MALDI, the signal recorded can be extremely complex and difficult to
      assign. Combining ion mobility with matrix-assisted laser desorption/ionization
      is a very powerful technique for fast separation and analysis of biomolecules in
      complex mixtures (such as tissue and cells), as isobaric lipid, peptide, and
      oligonucleotide molecular ions are pre-separated in the mobility cell before mass
      analysis. Differences in drift time of as much as 30% are obtained in a timescale
      of hundreds of microseconds. Molecular ions of the same biochemical family fall
      along trend lines when plotted in 2D plots of mobility drift time as a function
      of m/z. In this chapter ion mobility MALDI-MS ability to analyze various
      biomolecules in tissue, that is, lipids and proteins, as well as its ability to
      separate species from all of the major phospholipid classes from tissue and
      extracts, the effects that radyl chain length, degree of unsaturation, head group
      composition have upon their ion's cross section in the gas phase, and how it can
      be used not only to distinguish them from other biochemical groups in a mixture
      but also to differentiate them from other lipid species will be illustrated.

PMID- 20680587
TI  - Quantitative imaging of chemical composition in single cells by secondary ion
      mass spectrometry: cisplatin affects calcium stores in renal epithelial cells.
AB  - A detailed protocol for quantitative single cell mass spectrometry imaging (MSI)
      analysis is described in this chapter with examples of the treatment of cells
      with anticancer drug, cisplatin. Cisplatin, cis-diamminedichloridoplatinum ii
      (CDDP), is widely used for the treatment of many malignancies, including
      testicular, ovarian, bladder, cervical, head and neck, and small cell and non
      small cell lung cancers. The possibility of renal injury by cisplatin treatment
      is a major dose-limiting factor in this cancer therapy. At present, the
      mechanisms of cisplatin-induced renal cytotoxicity are poorly understood. In this
      work, secondary ion mass spectrometry (SIMS) was used for investigating cisplatin
      induced alterations in intracellular chemical composition in a well-established
      model (LLC-PK(1) cell line) for studying renal injury. The cells were
      cryogenically prepared by the sandwich freeze-fracture method for subcellular
      imaging analysis of chemical composition (total concentrations of K(+), Na(+),
      and Ca(2+)) in individual cells. The single cell analysis of these diffusible
      ions necessitates the use of reliable cryogenic sample preparations for SIMS. The
      sandwich freeze-fracture method offers a simple approach for cryogenically
      preserving diffusible ions and molecules inside the cells for SIMS analysis. A
      CAMECA IMS-3f SIMS ion microscope instrument capable of producing chemical images
      of single cells with 500-nm spatial resolution was used in the study. In
      cisplatin-treated cells, SIMS imaging showed the presence of detectable amount of
      platinum at mass 195, as (195)Pt(+) secondary ions in individual cells. SIMS
      observations also revealed that individual cells differed in their response to
      cisplatin. While the chemical composition of some cells was unaffected by
      cisplatin, others showed a reduction in cytoplasmic calcium stores that was not
      associated with changes in their intracellular K or Na concentrations. Another
      population of cells displayed an increase in cytoplasmic calcium concentration
      that was associated with higher levels of intracellular Na and a reduction in K
      concentration of the same cells. Since the loss of intracellular K and the gain
      of Na and Ca are typical symptoms of cell injury, it is plausible that the
      initial response of the cell to cisplatin treatment is the reduction in
      cytoplasmic calcium pool in stores. If, somehow, the calcium stores are
      compromised with cisplatin, then maintenance of free Ca(2+) homeostasis would
      become uncontrollable in the cell. These observations open new avenues of
      research for understanding of the mode of action of cisplatin in cell injury.
      This study also demonstrates the need and vast potential of single cell imaging
      mass spectrometry techniques in cell biology and medicine.

PMID- 20680588
TI  - Imaging MALDI mass spectrometry of sphingolipids using an oscillating capillary
      nebulizer matrix application system.
AB  - Matrix deposition is a critical step in tissue imaging by matrix-assisted laser
      desorption/ionization mass spectrometry (MALDI-MS). It greatly affects the
      quality of MALDI imaging, especially for the analytes (such as lipids) that may
      easily dissolve in the solvent used for the matrix application. This chapter
      describes the use of an oscillating capillary nebulizer (OCN) to spray small
      droplets of matrix aerosol onto the sample surface for improved matrix
      homogeneity, reduced crystal size, and controlled solvent effects. This protocol
      allows visualization of many different lipid species and, of particular interest,
      sphingolipids in tissue slices of Tay-Sachs/Sandhoff disease by imaging MALDI-MS.
      The structures of these lipids were identified by analysis of tissue extracts
      using electrospray ionization in conjunction with tandem mass spectrometry (MS/MS
      and MS(3)). These results illustrate the usefulness of tissue imaging MALDI-MS
      with matrix deposition by OCN for the molecular analysis in normal physiology and
      pathology. In addition, the observation of numerous lipid subclasses with
      distinct localizations in the brain slices demonstrates that imaging MALDI-MS
      could be effectively used for "lipidomic" studies.

PMID- 20680589
TI  - Mapping pharmaceuticals in rat brain sections using MALDI imaging mass
      spectrometry.
AB  - Matrix-assisted laser desorption/ionization-tandem mass spectrometric method
      (MALDI-MS/MS) has proven to be a reliable tool for direct measurement of the
      disposition of small molecules in animal tissue sections. As example, MALDI-MS/MS
      imaging system was employed for visualizing the spatial distribution of
      astemizole and its primary metabolite in rat brain tissues. Astemizole is a
      second-generation antihistamine, a block peripheral H1 receptor, which was
      introduced to provide comparable therapeutic benefit but was withdrawn in most
      countries due to toxicity risks. Astemizole was observed to be heterogeneously
      distributed to most parts of brain tissue slices including cortex, hippocampus,
      hypothalamic, thalamus, and ventricle regions while its major metabolite,
      desmethylastemizole, was only found around ventricle sites. We have shown that
      astemizole alone is likely to be responsible for the central nervous system (CNS)
      side effects when its exposures became elevated.

PMID- 20680590
TI  - Laser ablation electrospray ionization for atmospheric pressure molecular imaging
      mass spectrometry.
AB  - Laser ablation electrospray ionization (LAESI) is a novel method for the direct
      imaging of biological tissues by mass spectrometry. By performing ionization in
      the ambient environment, this technique enables in vivo studies with potential
      for single-cell analysis. A unique aspect of LAESI mass spectrometric imaging
      (MSI) is depth profiling that, in combination with lateral imaging, permits 3D
      molecular imaging for the first time under native conditions. With current
      lateral and depth resolutions of approximately 100 and approximately 40 microm,
      respectively, LAESI MSI helps to explore the molecular architecture of live
      tissues.

PMID- 20680591
TI  - Matrix-assisted laser desorption/ionization and nanoparticle-based imaging mass
      spectrometry for small metabolites: a practical protocol.
AB  - Matrix-assisted laser desorption/ionization (MALDI)-imaging mass spectrometry
      (IMS, also referred to as mass spectrometry imaging [MSI]) enables visualization
      of the distribution of biomolecules with varied and vast structures in tissue
      sections. This emerging imaging technique was initially developed as a tool for
      protein imaging; however, the number of studies reporting imaging of small
      organic molecules has recently increased. IMS is an effective technique for the
      visualization of endogenous small metabolites, especially lipids, facilitated by
      the unique advantages of mass spectrometry-based molecular detection. Despite the
      promising capability of MALDI-IMS for imaging small metabolites, this technique
      still has several issues, especially in spatial resolution. One of the critical
      limitations of the spatial resolution of MALDI-IMS is the size of the organic
      matrix crystal and the analyte migration during the matrix application process.
      To overcome these problems, we reported a nanoparticle (NP)-assisted laser
      desorption/ionization (nano-PALDI)-based IMS, in which the matrix crystallization
      process is eliminated. In this chapter, a practical protocol for MALDI-IMS of
      lipids is outlined. In addition, as an attractive alternative to MALDI-based IMS,
      we also present nanoparticle-based IMS that improves spatial resolution.

PMID- 20680592
TI  - Cellular imaging using matrix-enhanced and metal-assisted SIMS.
AB  - Imaging mass spectrometry (IMS) allows the direct investigation of both the
      identity and the spatial distribution of the entire molecular content directly in
      tissue sections, single cells, and many other biological surfaces. We describe
      here the steps required to retrieve the molecular information from tissue
      sections using matrix-enhanced (ME) and metal-assisted (MetA) secondary ion mass
      spectrometry (SIMS). Surface metallization by plasma coating enhances
      desorption/ionization of membrane components such as lipids and sterols in
      imaging time-of-flight (ToF) SIMS of tissues and cells. High-resolution images of
      cholesterol and other membrane components can be obtained for single
      neuroblastoma cells and reveal subcellular details. Alternatively, in ME-SIMS,
      2,5-dihydroxybenzoic acid electrosprayed on neuroblastoma cells allows intact
      molecular ion imaging of phosphatidylcholine (PC) and sphingomyelin (SM) at the
      cellular level.

PMID- 20680593
TI  - Tandem mass spectrometric methods for phospholipid analysis from brain tissue.
AB  - We describe the utility of intermediate-pressure MALDI and tandem mass
      spectrometry (MS/MS and MS( n )) for the characterization and imaging of
      phospholipids in brain tissue sections. The use of both MS/MS spectra and MS/MS
      images allows for identification of isobaric compounds. The structural
      characterization of phosphatidylcholines, phosphatidylserines,
      phosphatidylethanolamines, and sphingomyelins directly from tissue sections is
      described.

PMID- 20680594
TI  - Chemical imaging with desorption electrospray ionization mass spectrometry.
AB  - Desorption electrospray ionization mass spectrometry (DESI-MS) is a relatively
      new ambient surface analysis method. This technique requires little or no sample
      preparation prior to the actual analysis. Along with other application areas,
      DESI-MS is used to obtain chemical images of different biomolecules in biological
      tissue sections. In the case of biological tissue analysis, only preparation of
      the tissue slices is necessary. Furthermore, the method does not require the use
      of an ionization matrix preventing the redistribution of analytes prior to the
      analysis. Chemical images are obtained by monitoring the mass spectrometric
      signals of compounds while moving the sample relative to the DESI sprayer.

PMID- 20680595
TI  - Mass spectrometry imaging of small molecules using matrix-enhanced surface
      assisted laser desorption/ionization mass spectrometry (ME-SALDI-MS).
AB  - Surface-assisted laser desorption/ionization mass spectrometry (SALDI-MS) uses
      inorganic particles or porous surfaces as the energy-mediating means to promote
      desorption and ionization of low-mass analytes of interest. With good stability
      during laser ablation, SALDI substrates exhibit reduced background in the low
      mass region that is often crowded in conventional matrix-assisted laser
      desorption/ionization (MALDI) due to matrix fragmentation; a benefit renders
      SALDI-MS attractive in imaging low-mass species. Practical application of SALDI
      MS, however, is hindered by its unsatisfied detection sensitivity for most
      compounds. With aims of improving MS imaging resolution and sensitivity of low
      mass species, we describe an experimental protocol using a hybrid ionization
      method, termed matrix-enhanced SALDI (ME-SALDI), to detect crucial low-mass
      species with their spatial distribution in mouse brain tissue.

PMID- 20680596
TI  - Preparation of single cells for imaging mass spectrometry.
AB  - Characterizing the molecular contents of individual cells is critical for
      understanding fundamental mechanisms of biological processes. Imaging mass
      spectrometry (IMS) of biological systems has been steadily gaining popularity for
      its ability to create precise chemical images of biological samples, thereby
      revealing new biological insights and improving understanding of disease. In
      order to acquire mass spectral images from single cells that contain relevant
      molecular information, samples must be prepared such that cell-culture
      components, especially salts, are eliminated from the cell surface and that the
      cell contents are accessible to the mass spectrometer. We have demonstrated a
      cellular preparation technique for IMS that preserves the basic morphology of
      cultured cells, allows mass spectrometric chemical profiling of cytosol, and
      removes the majority of the interfering species derived from the cellular growth
      medium. Using this protocol, we achieve high-quality, reproducible IMS images
      from three diverse cell types: MCF7 human breast cancer cells, Madin-Darby canine
      kidney (MDCK) cells, and NIH/3T3 mouse fibroblasts. This preparation method
      allows rapid and routine IMS analysis of cultured cells, making possible a wide
      variety of experiments to further scientific understanding of molecular processes
      within individual cells.

PMID- 20680597
TI  - Applying imaging ToF-SIMS and PCA in differentiation of tissue types.
AB  - Time-of-flight secondary ion mass spectrometry (ToF-SIMS) has proven to be an
      extremely powerful tool for characterizing chemical distributions within
      biological cells and tissues. However, differentiating biological samples, e.g.,
      cancerous cells from their normal counterparts or benign tissues from malignant
      tissues, presents unique challenges to ToF-SIMS. Repeatable differentiation of
      such samples, especially formalin-fixed paraffin-embedded (FFPE) histological
      specimens, could be used to improve tissue-based diagnosis and aid in prognosis
      decisions. In this chapter, we describe a strategy for characterizing and
      differentiating FFPE tissues. ToF-SIMS was used to image deparaffinized FFPE
      mouse embryos and differentiate tissue types. The robustness and repeatability of
      the method was determined by analyzing ten tissue slices from three different
      embryos over a period of 1 month. Using principal component analysis (PCA) to
      reduce the spectral data generated by ToF-SIMS, histopathologically identified
      tissue types of the mouse embryos can be differentiated based on the
      characteristic differences in their mass spectra.

PMID- 20680598
TI  - Direct molecular analysis of whole-body animal tissue sections by MALDI imaging
      mass spectrometry.
AB  - The determination of the localization of various compounds in a whole animal is
      valuable for many applications, including pharmaceutical absorption,
      distribution, metabolism, and excretion (ADME) studies and biomarker discovery.
      Imaging mass spectrometry is a powerful tool for localizing compounds of
      biological interest with molecular specificity and relatively high resolution.
      Utilizing imaging mass spectrometry for whole-body animal sections offers
      considerable analytical advantages compared to traditional methods, such as whole
      body autoradiography, but the experiment is not straightforward. This chapter
      addresses the advantages and unique challenges that the application of imaging
      mass spectrometry to whole-body animal sections entails, including discussions of
      sample preparation, matrix application, signal normalization, and image
      generation. Lipid and protein images obtained from whole-body tissue sections of
      mouse pups are presented along with detailed protocols for the experiments.

PMID- 20680599
TI  - MALDI direct analysis and imaging of frozen versus FFPE tissues: what strategy
      for which sample?
AB  - Significant advances have been made in the past decade in the field of mass
      spectrometry imaging with MALDI ion sources (MALDI-MSI). While MALDI-MSI has high
      potential in the field of biology and in the clinic, a challenge for MALDI-MSI
      has been to adapt itself to a greater range of sample types. In particular, much
      of the biological archived materials for pathology studies are tissue biopsies
      fixed with paraformaldehyde and embedded in paraffin (FFPE tissues) because of
      the high stability of such samples. Thus, there has been a need to develop
      strategies for analyzing FFPE samples as this would allow retrospective studies
      of past clinical cases on large cohorts of existing samples. Obviously, PAF
      fixation, by inducing protein cross-linking, causes problems for molecular
      analysis by MS. We developed on tissue digestion strategies for overcoming these
      difficulties and allowing molecular data to be retrieved from FFPE samples no
      matter how long they have been stored. These digestion strategies preserve
      localization from digested proteins making MALDI-MSI of proteins possible by
      monitoring the resulting peptides. We present methods and protocols for FFPE
      samples. These strategies have proven to be valuable for all tested FFPE samples
      and have opened archived tissues from hospital banks to MALDI-MSI.

PMID- 20680600
TI  - On tissue protein identification improvement by N-terminal peptide
      derivatization.
AB  - Identification of potential markers of a physiological stage (e.g., pathology)
      discovered using MALDI-MSI is an important step in the understanding of signaling
      pathways or for providing sets of diagnosis and prognosis markers for clinical
      applications. Classically, identification can be achieved by extraction from a
      piece of tissue and proteomics strategies. However, this induces loss of
      information especially for low-abundance proteins or proteins localized to a
      specific region of the tissue. In this respect, identification directly at the
      tissue level is an attractive alternative. Because the molecular charge states in
      MALDI are low, on tissue identification is possible using bottom-up MALDI-MSI
      strategies. Enzymatic digestion using an enzyme such as trypsin can be performed
      at the micro-scale level to generate peptide collections while avoiding these
      peptides to be delocalized. It is, therefore, possible to image proteins through
      the molecular images of their digested peptides. These peptides can also be used
      to retrieve information on protein sequences by performing MS/MS, although
      databank interrogation or de novo sequencing using MS/MS spectra does not always
      lead to a successful or confident identification because on tissue complexities
      render PMF data problematic. Identification can be improved by increasing MS/MS
      spectra quality and simplifying their interpretation. This can be achieved by
      derivatization of peptides. In fact, derivatization of peptides leads to
      increases in fragmentation yields and orients fragmentations toward a specific
      series of fragment ions. In this respect, N-terminal chemical derivatization has
      proven to be particularly efficient. N-terminal chemical derivatization of
      tryptic peptides has been developed to be performed at the tissue level after on
      tissue digestion. Specific focus is given to 4-sulfophenyl isothiocyanate (4
      SPITC), 3-sulfobenzoic acid NHS ester (3-SBASE), and (N
      succinimidyloxycarbonylmethyl)tris(2,4,6-trimethoxyphenyl)phosphonium bromide
      (TMPP) derivatizations. This provides a complete strategy for protein
      identification in a bottom-up MALDI-MSI approach and opens the way for novel
      biomarker identification.

PMID- 20680601
TI  - Specific MALDI-MSI: Tag-Mass.
AB  - MALDI imaging as a molecular mass spectrometry imaging technique (MSI) can
      provide accurate information about molecular composition on a surface. The last
      decade of MSI development has brought the technology to clinical and biomedical
      applications as a complementary technique of MRI and other molecular imaging.
      Then, this IMS technique is used for endogenous and exogenous molecule detection
      in pharmaceutical and biomedical fields. However, some limitations still exist
      due to physical and chemical aspects, and sensitivity of certain compounds is
      very low. Thus, we developed a multiplex technique for fast detection of
      different compound natures. The multiplex MALDI imaging technique uses a
      photocleavable group that can be detect easily by MALDI instrument. These
      techniques of targeted imaging using Tag-Mass molecules allow the multiplex
      detection of compounds like antibodies or oligonucleotides. Here, we describe how
      we used this technique to detect huge proteins and mRNA by MALDI imaging in rat
      brain and in a model for regeneration; the leech.

PMID- 20680602
TI  - Structurally selective imaging mass spectrometry by imaging ion mobility-mass
      spectrometry.
AB  - This chapter describes the utility of structurally based separations combined
      with imaging mass spectrometry (MS) by ion mobility-MS (IM-MS) approaches. The
      unique capabilities of combining rapid (mus-ms) IM separations with imaging MS
      are detailed for an audience ranging from new to potential practitioners in IM-MS
      technology. Importantly, imaging IM-MS provides the ability to rapidly separate
      and elucidate various types of endogenous and exogenous biomolecules (e.g.,
      nucleotides, carbohydrates, peptides, and lipids), including isobaric species.
      Drift tube and traveling wave IM-MS instrumentation are described and specific
      protocols are presented for calculating ion-neutral collision cross sections
      (i.e., apparent ion surface area or structure) from experimentally obtained IM-MS
      data. Special emphasis is placed on the use of imaging IM-MS for the analysis of
      samples in life sciences research (e.g., thin tissue sections), including
      selective imaging for peptide/protein and lipid distributions. Future directions
      for rapid and multiplexed imaging IM-MS/MS are detailed.

PMID- 20680603
TI  - Tutorial: multivariate statistical treatment of imaging data for clinical
      biomarker discovery.
AB  - Cancer research is one of the most promising application areas for the new
      technology of MALDI tissue imaging. Cancerous tissue can easily be distinguished
      from healthy tissue by dramatically changed metabolism, growth, and apoptotic
      processes. Of even higher interest is the fact that MALDI imaging allows to
      unveil molecular differentiation undetectable by classical histological
      techniques. Thus, MALDI imaging has tremendous potential as a tool to
      characterize the therapeutic susceptibility of tumors in biopsies as well as to
      predict tumor progression in endpoint studies. However, some aspects are
      important to consider for a successful MALDI imaging-based cancer research.
      Cancer sections are usually very heterogeneous - different biochemical pathways
      can be active in individual tumor clones, at different development stages or in
      various tumor microenvironments. Understanding tissue at this level is only
      possible for experienced histopathologists working on high-resolution optical
      images. Therefore, the largest benefit from the use of MALDI imaging results in
      histopathology will arise if molecular images are related to classical high
      resolution histological images in a simple way without the need to interpret mass
      spectra directly. Each MALDI imaging data set effectively provides information on
      hundreds of molecules and permits the generation of molecular images displaying
      the relative abundance of these molecules across the tissue. The interpretation
      of these in the histological context is a major challenge in terms of expert
      analysis time. This is true especially for clinical work with hundreds of tissue
      specimens to be analyzed by MALDI, interpreted, and compared. Therefore, a MALDI
      imaging workflow is described here that enables fast and unambiguous
      interpretation of the MALDI imaging data in the histological context.
      Preprocessing of the image data using statistical tools allows efficient and
      straightforward interpretation by the histopathologist. In this chapter, we
      explain the use of principal component analysis (PCA) and hierarchical clustering
      (HC) for the efficient interpretation of MALDI imaging data. We also outline how
      these methods can be used to compare specific disease states between patients in
      the search for biomarkers.

PMID- 20680604
TI  - Applications of MALDI-MSI to pharmaceutical research.
AB  - MALDI-MSI has been demonstrated to be a suitable technique in pharmaceutical
      research for providing information of the distribution of low molecular weight
      compounds such as drugs and their metabolites within whole-body tissue sections.
      Important ADME information can be determined by MALDI-MSI analysis of the
      distribution of drugs and metabolites in whole-body tissue sections taken from
      animals killed at a range of time points postdose. In this example we applied
      MALDI-MSI to the localization of a compound and its primary metabolite in whole
      body mouse sections.

PMID- 20680605
TI  - Tissue preparation for the in situ MALDI MS imaging of proteins, lipids, and
      small molecules at cellular resolution.
AB  - The resolution of MALDI MS imaging is limited by the displacement of analytes
      during matrix deposition or by laser focal diameter. Here we present three
      methods that minimize the displacement of analytes during matrix deposition,
      including a method where image resolution is not limited by the laser focal
      diameter. The first method, matrix solution fixation, simultaneously fixes tissue
      while depositing matrix and is optimal for analyzing proteins and for
      applications requiring a fast preparation time. This method is characterized by
      compatibility with histology methods and laser focal diameter-limited resolution.
      The second method, a sensor controlled aerosol, is characterized by aerosol
      droplet size-limited resolution and is optimal for small molecules, including
      lipids, peptides, and drug-like molecules. The third method, microinjection with
      matrix, selectively deposits matrix upon cells of interest, offers cellular
      resolution and is compatible with most analytes. A flow chart summarizing methods
      is provided so that users may design a tissue preparation strategy based upon
      their resources and experimental goals.

PMID- 20680606
TI  - Imaging of similar mass neuropeptides in neuronal tissue by enhanced resolution
      MALDI MS with an ion trap - Orbitrap hybrid instrument.
AB  - Several mass spectrometry imaging (MSI) procedures are used to localize
      physiologically active peptides in neuronal tissue from American cockroach
      (Periplaneta americana) neurosecretory organs. We report how to use this model
      system to assess, for the first time, the performance of the MALDI LTQ Orbitrap
      XL mass spectrometer to perform MSI of secretory neuropeptides. The method
      involves the following steps: (1) rapid dissecting of neurosecretory tissue
      (i.e., insect neurohemal organ) in isotonic sucrose solution; (2) mounting the
      tissue on a glass slide; (3) controlled spraying of the air-dried tissue with
      concentrated MALDI matrix solution; (4) loading specimen into the MALDI source of
      a MS(n) system equipped with an Orbitrap analyzer; (5) setting-up MSI methods by
      determining tissue areas of interest, spatial resolution, molecular mass range,
      and molecular mass resolution; (6) acquiring mass spectra; (7) analyzing data
      using ImageQuest MSI software to generate (single or composite) images of the
      distribution of peptide(s) of interest; (8) confirming the identity of selected
      peptides by MS(2) and/or MS( n ) sequencing directly from imaged tissue sample.
      The results illustrate that high mass accuracy and high mass resolving power of
      the Orbitrap analyzer are achievable in analyses directly from tissue, such as in
      MSI experiments. Moreover the mass spectrometric instrumentation evaluated allows
      for both peptide localization and peptide identification/sequencing directly from
      tissue.

PMID- 20680607
TI  - Mass spectrometric imaging of neuropeptides in decapod crustacean neuronal
      tissues.
AB  - The emerging technology mass spectrometric imaging (MSI) provides an attractive
      opportunity to detect and probe the molecular content of tissues in an anatomical
      context. This powerful methodology has been applied extensively to the
      localization of proteins, peptides, pharmaceuticals, metabolites, lipids, and
      other biological and chemical compounds in tissues. Herein, we present a method
      developed specifically for mapping neuropeptides in crustacean neuronal tissues.
      Both cryostat tissue sectioning and whole-mount tissue blotting techniques are
      highlighted. Careful sample preparation is essential for obtaining sufficient
      analyte/matrix mixing while retaining the spatial localization of the
      neuropeptides. Several matrix application apparatus and techniques are described
      and compared. Furthermore, three-dimensional (3D) imaging has been developed to
      provide detailed information about the distribution of neuropeptides within 3D
      structure of a crustacean brain.

PMID- 20680608
TI  - Mass spectrometry imaging using the stretched sample approach.
AB  - Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging
      (MSI) can determine tissue localization for a variety of analytes with high
      sensitivity, chemical specificity, and spatial resolution. MS image quality
      typically depends on the MALDI matrix application method used, particularly when
      the matrix solution or powder is applied directly to the tissue surface. Improper
      matrix application results in spatial redistribution of analytes and reduced MS
      signal quality. Here we present a stretched sample imaging protocol that removes
      the dependence of MS image quality on the matrix application process and improves
      analyte extraction and sample desalting. First, the tissue sample is placed on a
      monolayer of solid support beads that are embedded in a hydrophobic membrane.
      Stretching the membrane fragments the tissue into thousands of nearly single-cell
      sized islands, with the pieces physically isolated from each other by the
      membrane. This spatial isolation prevents analyte transfer between beads,
      allowing for longer exposure of the tissue fragments to the MALDI matrix, thereby
      improving detectability of small analyte quantities without sacrificing spatial
      resolution. When using this method to reconstruct chemical images, complications
      result from non-uniform stretching of the supporting membrane. Addressing this
      concern, several computational tools enable automated data acquisition at
      individual bead locations and allow reconstruction of ion images corresponding to
      the original spatial conformation of the tissue section. Using mouse pituitary,
      we demonstrate the utility of this stretched imaging technique for characterizing
      peptide distributions in heterogeneous tissues at nearly single-cell resolution.

PMID- 20680609
TI  - A robust molecular marker for the detection of shortened introgressed segment
      carrying the stem rust resistance gene Sr22 in common wheat.
AB  - Stem rust resistance gene Sr22 transferred to common wheat from Triticum
      boeoticum and T. monococcum remains effective against commercially prevalent
      pathotypes of Puccinia graminis f. sp. tritici, including Ug99 and its
      derivatives. Sr22 was previously located on the long arm of chromosome 7A.
      Several backcross derivatives (hexaploid) possessing variable sized Sr22-carrying
      segments were used in this study to identify a closely linked DNA marker.
      Expressed sequenced tags belonging to the deletion bin 7AL-0.74-0.86,
      corresponding to the genomic location of Sr22 were screened for polymorphism. In
      addition, RFLP markers that mapped to this region were targeted. Initial
      screening was performed on the resistant and susceptible DNA bulks obtained from
      backcross derivatives carrying Sr22 in three genetic backgrounds with short T.
      boeoticum segments. A cloned wheat genomic fragment, csIH81, that detected RFLPs
      between the resistant and susceptible bulks, was converted into a sequence tagged
      site (STS) marker, named cssu22. Validation was performed on Sr22 carrying
      backcross-derivatives in fourteen genetic backgrounds and other genotypes used
      for marker development. Marker cssu22 distinguished all backcross-derivatives
      from their respective recurrent parents and co-segregated with Sr22 in a
      Schomburgk (+Sr22)/Yarralinka (-Sr22)-derived recombinant inbred line (RIL)
      population. Sr22 was also validated in a second population, Sr22TB/Lakin-derived
      F(4) selected families, containing shortened introgressed segments that showed
      recombination with previously reported flanking microsatellite markers.

PMID- 20680610
TI  - Fine mapping QMi-C11 a major QTL controlling root-knot nematodes resistance in
      Upland cotton.
AB  - The identification and utilization of a high-level of host plant resistance is
      the most effective and economical approach to control root-knot nematode
      (Meloidogyne incognita). In an earlier study, we identified a major quantitative
      trait locus (QTL) for resistance to root-knot nematode in the M-120 RNR Upland
      cotton line (Gossypium hirsutum L.) of the Auburn 623 RNR source. The QTL is
      located in a 12.9-cM interval flanked by the two SSR markers CIR069 and CIR316 on
      the distal segment of chromosome 11. To construct a fine map around the target
      region, a bulked segregation analysis was performed using two DNA pools
      consisting of five individuals, with each being homozygous for the two parental
      alleles. From a survey of 1,152 AFLP primer combinations, 9 AFLP markers closely
      linked to the target region were identified. By screening an additional 1,221
      F(2) individuals developed from the initial mapping population, the Mi-C11 locus
      was delimited to a 3.6-cM interval flanked by the SSR marker CIR069 and the AFLP
      marker E14M27-375. These results further elucidate the genetic fine structure of
      the Mi-C11 locus and provide the basis for map-based isolation of the nematode
      resistance gene in M-120 RNR.

PMID- 20680611
TI  - High-resolution mapping of the brown planthopper resistance gene Bph6 in rice and
      characterizing its resistance in the 9311 and Nipponbare near isogenic
      backgrounds.
AB  - Brown planthopper (Nilaparvata lugens Stal, BPH) is one of the most destructive
      insect pests of rice. Exploring resistance genes from diverse germplasms and
      incorporating them into cultivated varieties are critical for controlling this
      insect. The rice variety Swarnalata was reported to carry a resistance gene
      (designated Bph6), which has not yet been assigned to a chromosome location and
      the resistance mechanism is still unknown. In this study, we identified and
      mapped this gene using the F(2) and backcrossing populations and characterized
      its resistance in indica 9311 and japonica Nipponbare using near isogenic lines
      (NILs). In analysis of 9311/Swarnalata F(2) population, the Bph6 gene was located
      on the long arm of chromosome 4 between the SSR markers RM6997 and RM5742. The
      gene was further mapped precisely to a 25-kb region delimited between the STS
      markers Y19 and Y9; and the distance between these markers is 25-kb in Nipponbare
      genome. The Bph6 explained 77.5% of the phenotypic variance of BPH resistance in
      F(2) population and 84.9% in BC(2)F(2) population. Allele from Swarnalata
      significantly increased resistance to the BPH, resulted in a reduced damage
      score. In characterization of Bph6-mediated resistance, the BPH insects showed
      significant preference between NIL-9311 and 9311 in 3 h and between NIL-NIP and
      Nipponbare in 120 h after release. BPH growth and development were inhibited, and
      the insect's survival rates were lower on Bph6-NIL plants, compared with the
      parents 9311 and Nipponbare. The results indicate that the Bph6 exerted prolonged
      antixenotic and antibiotic effects in Bph6-NIL plants, and NIL-9311 plants showed
      a quicker and stronger effect toward BPH than NIL-NIP plants.

PMID- 20680612
TI  - hi2-1, a QTL which improves harvest index, earliness and alters metabolite
      accumulation of processing tomatoes.
AB  - Harvest index, defined as the ratio of reproductive yield to total plant biomass,
      and early ripening are traits with important agronomic value in processing
      tomatoes. The Solanum pennellii introgression-line (IL) population shows
      variation for harvest index and earliness. Most of the QTL mapped for these
      traits display negative agronomic effects; however, hi2-1 is a unique QTL
      displaying improved harvest index and earliness. This introgression was tested
      over several years and under different genetic backgrounds. Thirty-one nearly
      isogenic sub-lines segregating for the 18 cM TG33-TG276 interval were used for
      fine mapping of this multi-phenotypic QTL. Based on this analysis the phenotypic
      effects for plant weight, Brix, total yield and earliness were co-mapped to the
      same region. In a different mapping experiment these sub-lines were tested as
      heterozygotes in order to map the harvest index QTL which were only expressed in
      the heterozygous state. These QTL mapped to the same candidate region, suggesting
      that hi2-1 is either a single gene with pleiotropic effects or represents linked
      genes independently affecting these traits. Metabolite profiling of the fruit
      pericarp revealed that a number of metabolic QTL co-segregate with the harvest
      index trait including those for important transport assimilates such as sugars
      and amino acids. Analysis of the flowering pattern of these lines revealed
      induced flowering at IL2-1 plants, suggest that hi2-1 may also affect harvest
      index and early ripening by changing plant architecture and flowering rate.

PMID- 20680613
TI  - Time course of ethanol and propofol exhalation after bolus injection using ion
      molecule reaction-mass spectrometry.
AB  - The transit of ethanol from blood to breath gas is well characterised. It is used
      for intraoperative monitoring and in forensic investigations. A further
      substance, which can be measured in breath gas, is the phenol propofol. After a
      simultaneous bolus injection, the signals (time course and amplitude) of ethanol
      and propofol in breath gas were detected by ion molecule reaction-mass
      spectrometry (IMR-MS) and compared. After approval by the regional authorities,
      eight pigs were endotracheally intubated after a propofol-free induction with
      etomidate. Boluses of ethanol (16 MUg/kg) and propofol (4 or 2 mg/kg) were
      infused alone and in combination. For both substances, breath gas concentrations
      were continuously measured by IMR-MS; the delay time, time to peak and amplitude
      were determined and compared using non-parametric statistic tests. IMR-MS allows
      a simultaneous continuous measurement of both substances in breath gas. Ethanol
      appeared (median delay time, 12 vs 29.5 s) and reached its peak concentration
      (median time to peak, 45.5 vs 112 s) significantly earlier than propofol. Time
      courses of ethanol and propofol in breath gas can be simultaneously described
      with IMR-MS. Differing pharmacological and physicochemical properties of the two
      substances can explain the earlier appearance and time to peak of ethanol in
      breath gas compared with propofol.

PMID- 20680614
TI  - Cardiolipin, a key component to mimic the E. coli bacterial membrane in model
      systems revealed by dynamic light scattering and steady-state fluorescence
      anisotropy.
AB  - The phase transition temperatures of several lipidic systems were determined
      using two different techniques: dynamic light scattering (DLS) and steady-state
      fluorescence anisotropy, using two fluorescent probes that report different
      membrane regions (TMA-DPH and DPH). Atomic force microscopy (AFM) was used as a
      complementary technique to characterize different lipid model systems under
      study. The systems were chosen due to the increased interest in bacterial
      membrane studies due to the problem of antibiotic drug resistance. The simpler
      models studied comprised of mixtures of POPE and POPG lipids, which form a
      commonly used model system for Escherichia coli membranes. Given the important
      role of cardiolipin (CL) in natural membranes, a ternary model system,
      POPE/POPG/CL, was then considered. The results obtained in these mimetic systems
      were compared with those obtained for the natural systems E. coli polar and total
      lipid extract. DLS and fluorescence anisotropy are not commonly used to study
      lipid phase transitions, but it was shown that they can give useful information
      about the thermotropic behaviors of model systems for bacterial membranes. These
      two techniques provided very similar results, validating their use as methods to
      measure phase transitions in lipid model systems. The temperature transitions
      obtained from these two very different techniques and the AFM results clearly
      show that cardiolipin is a fundamental component to mimic bacteria membranes. The
      results suggest that the less commonly used ternary system is a considerably
      better mimic for natural E. coli membranes than binary lipid mixture.

PMID- 20680615
TI  - Characterization of currently marketed heparin products: key tests for quality
      assurance.
AB  - During the 2007-2008 heparin crisis, it was found that the United States
      Pharmacopeia (USP) testing monograph for unfractionated heparin sodium (UFH) did
      not detect the presence of the contaminant, oversulfated chondroitin sulfate
      (OSCS) in heparin. In response to this concern, new tests and specifications were
      developed by the Food and Drug Administration (FDA) and USP and put in place to
      not only detect the contaminant OSCS but also to improve assurance of quality and
      purity of the drug product. Additional tests were also developed to monitor the
      heparin supply chain for other possible economically motivated additives or
      impurities. In 2009, a new USP monograph was put in place that includes 500 MHz
      (1)H NMR, SAX-HPLC, %galactosamine in total hexosamine, and anticoagulation time
      assays with purified factor IIa or factor Xa. These tests represent orthogonal
      approaches for UFH identification, measurement of bioactivity, and for detection
      of process impurities or contaminants in UFH. The FDA has applied these
      analytical approaches to the study of UFH active pharmaceutical ingredients in
      the marketplace. Here, we describe results from a comprehensive survey of UFH
      collected from seven different sources after the 2009 monograph revision and
      compare these data with results obtained on other heparin samples collected
      during the 2007-2008 crisis.

PMID- 20680617
TI  - Development of a micro-total analysis system (MU-TAS) for the determination of
      catecholamines.
AB  - In this study, the first micro-total analysis system (MU-TAS) for catecholamines
      (dopamine, epinephrine, and norepinephrine) analysis in which preconcentration,
      separation, and determination steps were integrated on a microchip was developed.
      Electrophoresis microchips in a variety of channel lengths and designs were
      produced in borofloat glass for the MU-TAS studies. Chambers for the preparation
      of monolithic disks were formed in the microchips at the intersection of the
      injection and separation channels. Vinyl phenylboronic acid-ethylene glycol
      dimethacrylate polymers were prepared as monolithic disks in these chambers with
      a depth of 0.05 mm and a diameter of 2.1 mm. The microchips could be used more
      than 50 times if mechanical problems such as plugging or fracturing did not
      occur. Adsorption and elution of catecholamines were realized electrokinetically,
      with catecholamines determined via laser-induced native fluorescence detection
      following elution and electrophoretic separation. The most promising results were
      obtained with 100 mM phosphate buffer (pH 2) for elution with 25% propanol added
      to the separation buffer (100 mM phosphate, pH 3).

PMID- 20680616
TI  - Sizing up the future of microRNA analysis.
AB  - In less than 20 years, our appreciation for micro-RNA molecules (miRNAs) has
      grown from an original, curious observation in worms to their current status as
      incredibly important global regulators of gene expression that play key roles in
      many transformative biological processes. As our understanding of these small,
      non-coding transcripts continues to evolve, new approaches for their analysis are
      emerging. In this critical review we describe recent improvements to classical
      methods of detection as well as innovative new technologies that are poised to
      help shape the future landscape of miRNA analysis.

PMID- 20680618
TI  - Emerging food contaminants: a review.
AB  - Governments throughout the world are intensifying their efforts to improve food
      safety. These efforts come as a response to an increasing number of food-safety
      problems and increasing consumer concerns. In addition, the variety of toxic
      residues in food is continuously increasing as a consequence of industrial
      development, new agricultural practices, environmental pollution, and climate
      change. This paper reviews a selection of emerging contaminants in food,
      including the industrial organic pollutants perfluorinated compounds (PFCs),
      polybrominated diphenyl ethers (PBDEs), and nanomaterials; the pharmaceutical
      residues antibiotics and coccidiostats; and emerging groups of marine biotoxins.
      The main analytical approaches for their detection and quantification in food
      will be presented and discussed with special emphasis on biological techniques,
      when these are feasible. In the last section, a summary of recent publications
      reporting the concentrations of these compounds in food will be presented and
      discussed.

PMID- 20680619
TI  - De novo evolution of complex, global and hierarchical gene regulatory mechanisms.
AB  - Gene regulatory networks exhibit complex, hierarchical features such as global
      regulation and network motifs. There is much debate about whether the
      evolutionary origins of such features are the results of adaptation, or the by
      products of non-adaptive processes of DNA replication. The lack of availability
      of gene regulatory networks of ancestor species on evolutionary timescales makes
      this a particularly difficult problem to resolve. Digital organisms, however, can
      be used to provide a complete evolutionary record of lineages. We use a
      biologically realistic evolutionary model that includes gene expression,
      regulation, metabolism and biosynthesis, to investigate the evolution of complex
      function in gene regulatory networks. We discover that: (i) network architecture
      and complexity evolve in response to environmental complexity, (ii) global gene
      regulation is selected for in complex environments, (iii) complex, inter
      connected, hierarchical structures evolve in stages, with energy regulation
      preceding stress responses, and stress responses preceding growth rate
      adaptations and (iv) robustness of evolved models to mutations depends on
      hierarchical level: energy regulation and stress responses tend not to be robust
      to mutations, whereas growth rate adaptations are more robust and non-lethal when
      mutated. These results highlight the adaptive and incremental evolution of
      complex biological networks, and the value and potential of studying realistic in
      silico evolutionary systems as a way of understanding living systems.

PMID- 20680620
TI  - Rib head protrusion into the central canal in type 1 neurofibromatosis.
AB  - BACKGROUND: Intraspinal rib head dislocation is an important but under-recognized
      consequence of dystrophic scoliosis in patients with neurofibromatosis 1 (NF1).
      OBJECTIVE: To present clinical and imaging findings of intraspinal rib head
      dislocation in NF1. MATERIALS AND METHODS: We retrospectively reviewed clinical
      presentation, imaging, operative reports and post-operative courses in four NF1
      patients with intraspinal rib head dislocation and dystrophic scoliosis. We also
      reviewed 17 cases from the English literature. RESULTS: In each of our four cases
      of intraspinal rib head dislocation, a single rib head was dislocated on the
      convex apex of the curve, most often in the mid- to lower thoracic region. Cord
      compression occurred in half of these patients. Analysis of the literature
      yielded similar findings. Only three cases in the literature demonstrates the MRI
      appearance of this entity; most employ CT. All of our cases include both MRI and
      CT; we review the subtle findings on MRI. CONCLUSION: Although intraspinal rib
      head dislocation is readily apparent on CT, sometimes MRI is the only cross
      sectional imaging performed. It is essential that radiologists become familiar
      with this entity, as subtle findings have significant implications for surgical
      management.

PMID- 20680622
TI  - Recognition of fibrous dysplasia of bone mimicking skeletal metastasis on 18F-FDG
      PET/CT imaging.
AB  - PURPOSE: Fibrous dysplasia of bone (FDB) reveals intense 18F-FDG uptake mimicking
      metastases on 18F-FDG PET/CT. We reviewed sites of FDB revealed by 18F-FDG PET/CT
      imaging to allow identification of this abnormality. MATERIALS AND METHODS:
      Eleven patients (7 male, 4 female, aged 16-78 years) were evaluated after 55 MBq
      (0.15 mCi)/kg 18F-FDG utilizing a 16-slice multiple detector CT (MDCT) whole-body
      PET scanner, with LOR algorithm 3D reconstruction. One- and 2-h imaging was
      performed in 9 patients. Standard uptake value (SUV) for each lesion, on early
      and delayed imaging, was calculated. Lesions were confirmed in 6 patients by
      biopsy. The PET images correlated with MDCT to establish the imaging
      characteristics. RESULTS: Solitary lesions were found in 4 patients, two lesions
      in 1 patient, and in 6 patients there were multiple bone lesions. The SUV(early)
      ranged from 1.23 to 9.64 with an average of 3.76 +/- 2.40. The SUV(delayed)
      ranged from 1.76 to 11.42 with an average of 4.51 +/- 3.07. The SUV(delayed)
      decreased or increased slightly (-31% to 5%) in 6 of our patients, and increased
      significantly (11% to 39%) in 3. There was a negative correlation between SUVs
      and age, as well as the number of affected bones. CONCLUSIONS: In our study, FDB
      had wide skeletal distribution with variability of 18F-FDG uptake and CT
      appearance. SUV in the delayed stage was seen to either decrease or increase on
      dual-time 18F-FDG PET scanning. It is very important to recognize the
      characteristics of this skeletal dysplasia to allow differentiation from skeletal
      metastasis.

PMID- 20680621
TI  - Molecular ultrasound imaging and its potential for paediatric radiology.
AB  - US is a low-cost, real-time imaging modality that is the most used diagnostic
      tool in paediatric radiology. Reasons include the improved US image quality in
      children as compared to adults and the demand for avoiding X-rays as much as
      possible because children are more sensitive to radiation than adults. Stabilized
      microbubbles have been approved as US contrast agents for adults and show great
      potential in improving the diagnostic accuracy for many diseases. Initial studies
      show that in paediatric radiology contrast-enhanced US could also be beneficial
      for more than just the diagnosis of vesicoureteral reflux, if US contrast agents
      were approved for children. Molecular US imaging utilizes microbubbles conjugated
      to biomolecules that target intravascular disease-specific molecules. Many
      preclinical studies show that molecular US imaging is a highly sensitive tool to
      detect neovascularisation, inflammation and cardiovascular diseases. Its main
      advantages are the higher informative value, the longer persistence of the label
      at the target lesion and the chance to work with lower contrast agent dosages.
      Now, clinical translation of molecular US appears at the horizon. This review
      article reports on the current status of molecular US imaging and discusses its
      potential for paediatric radiology.

PMID- 20680623
TI  - New observations on meniscal cysts.
AB  - OBJECTIVE: The purpose of this study was to determine the incidence of meniscal
      cysts, assess the frequency of various magnetic resonance (MR) imaging
      characteristics, and emphasize radiographic observations not commonly reported.
      MATERIALS AND METHODS: A total of 2,095 consecutive knee MR imaging reports from
      a 22 month period were retrospectively reviewed for the presence of meniscal
      cysts. Two musculoskeletal radiologists reviewed the cases where cysts were
      reported. A meniscal cyst was considered present if abnormally increased signal
      was identified within an enlarged meniscus (i.e., intrameniscal cyst) or if a
      loculated fluid-intensity lesion with a clear connection to the adjacent meniscus
      was identified (i.e., parameniscal cyst). Presence or absence of a meniscal tear,
      intrameniscal and parameniscal signal intensity, patient age, sex, location of
      meniscal cyst, presence of discoid meniscus, and size of the parameniscal cyst
      component were recorded. All knee imaging examinations were performed on a 1.5T
      MR unit. Imaging findings were correlated with arthroscopic reports when
      available. RESULTS: A total of 167 cases (8.0%) of meniscal cysts were diagnosed
      in 161 patients. Of the 167 cysts, 69 (41.3%) were located in the lateral
      meniscus and 98 (58.7%) in the medial meniscus. In 6 patients (3.7%), meniscal
      cysts were present in both menisci of the same knee. Twelve (7.2%) meniscal cysts
      were associated with discoid menisci. Ninety-seven (57.8%) meniscal cysts were
      associated with meniscal tears. Of the total number of meniscal cysts, 104
      (62.3%) had a parameniscal cyst. An isolated intrameniscal cyst was present in 63
      (37.7%) cases. One hundred (96%) of the parameniscal cyst components were
      isointense to fluid on T2-weighted FSE images. All cysts exhibited abnormal
      intrameniscal signal. Only 14 (8.4%) of the intrameniscal components were
      isointense to fluid on T2-weighted FSE images. The arthroscopic reports of 88 of
      the 161 (54.7%) patients were available for review and correlation. A tear
      extending to the articular surface of the meniscus was reported to be present in
      74 of the 88 (84%) arthroscopic examinations. CONCLUSIONS: Knowledge of the
      spectrum of findings and the relative frequency of various MR imaging
      characteristics as well as common potential pitfalls is important to the accurate
      diagnosis and management of mensical cysts. In particular, controversy exists as
      to the incidence of articular surface tears in association with meniscal cysts,
      with some authors reporting greater than 98% correlation with tears. Only 58% of
      cysts were associated with an articular surface tear. Ninety six percent of the
      parameniscal signal was isointense to fluid, only 8% of the intramensical signal
      was isointense to fluid.

PMID- 20680624
TI  - Indeterminate soft-tissue tumors of the hand and wrist: a review based on a
      clinical series of 39 cases.
AB  - Soft-tissue masses located at the hand and wrist are a frequent clinical
      presentation. The majority of these are ganglia, which have characteristic
      imaging features. Other common masses in which a diagnosis is suggested by
      imaging include hemangiomas, lipomas, and focal synovitis. The remainder are rare
      although a diagnosis may be attempted by considering the patients' age and the
      location. We reviewed 39 soft-tissue masses at the hand and wrist referred to our
      institution between September 1998 and January 2006 that had indeterminate
      imaging features. The majority were benign neoplastic lesions with the most
      common being a giant cell tumor of the tendon sheath, followed by angioleiomyoma,
      peripheral nerve sheath tumor, fibromatosis, fibroma of tendon sheath, and
      solitary fibrous tumor. These lesions tend to occur in young adults at the
      metacarpal level. However, there are no imaging features that can reliably
      differentiate between benign and malignant tumors.

PMID- 20680625
TI  - Ilizarov for radiologists.
AB  - If you had a choice, you would probably not wish to undergo Ilizarov treatment;
      it is a long and stressful treatment and requires considerable effort. If you
      have a major deformity, massive bone loss or complex bone infection, however, the
      other options are even less appealing. Large allografts have high rates of
      infection, non-union and late fracture, and metal implants are at risk of
      loosening and fatigue particularly in younger patients. Sometimes the only other
      option is an amputation. The Ilizarov method offers the ability to correct
      deformity and grow new, normal bone which will continue to serve its purpose for
      the rest of your life.

PMID- 20680626
TI  - Submandibular neck lifting with platysma resection.
AB  - A novel method for cervicofacial rejuvenation by submandibular neck lifting with
      platysma resection is presented. Between 2003 and 2009 we performed submandibular
      neck lifting in 18 cases. This technique is an isolated but efficient procedure
      for lifting of the neck. An additional advantage might be the possibility of
      doing the procedure with tumescence local anesthesia. In all cases, satisfactory
      aesthetic results were achieved.

PMID- 20680627
TI  - The use of IntegraTM in rhinoplasty.
AB  - Different biosynthesized materials and autologous grafts have been used for many
      years to increase the size or to change the shape of the nasal dorsum in
      augmentation rhinoplasty. To avoid the undesirable effects of these materials,
      such as reabsorption, intolerance, granulomas, visualization of the graft's
      edges, and the migration of the implant, a new technique is proposed that uses a
      dermic regeneration template (IntegraTM). The authors have performed 56 surgeries
      for patients with different indications, and 30 of these patients have been
      followed up for a minimum of 12 months. The advantage of using this template, a
      sheet comprising a porous matrix of collagen fibers and glycosaminoglycans, is
      that it provides a structure for autologous dermic tissue regeneration. Its
      handling versatility once the silicone sheet is removed allows it to be folded
      over itself until the needed thickness is obtained as well as the desired
      aesthetic results. The authors believe that the dermic regeneration template
      (IntegraTM) is a good alternative filler material because it is completely
      reabsorbed and replaced by autologous dermis. The action is not to replace but to
      help the development of the patient's own tissue, avoiding a possible intolerance
      because it does not act as a foreign body. The volume remains stable throughout
      time, and overcorrection is not necessary.

PMID- 20680628
TI  - Thinning pine plantations to reestablish oak openings species in northwestern
      Ohio.
AB  - Globally the area in forest plantations is rising by 2% annually, increasing the
      importance of plantations for production of human goods and services and for
      ecological functions such as carbon storage and biodiversity conservation.
      Specifically in the Great Lakes states and provinces of Midwestern North America,
      thousands of hectares of pine plantations were established in the early and mid
      1900s to revegetate abandoned agricultural fields that had replaced mixed-species
      forests and oak-prairie ecosystems. Plantation establishment also was intended to
      bolster the timber base. Management priorities have shifted, with many resource
      managers currently seeking to manage existing plantations for promoting mixed
      species ecosystems. The purpose of this study was to assess plant succession and
      the reestablishment of oak savanna and prairie species after thinning 14
      plantations of Pinus resinosa and strobus in northwestern Ohio, USA. Thinning
      reduced tree basal area by an average of 75%. Plant communities were sampled on
      0.05-ha plots one and 3 years after thinning and compared to 10 unthinned control
      plantations. By 3 years after thinning, thinned plots contained 2-3 times more
      species and 14 times more plant cover than control plots. The species composition
      of colonizing plants was most strongly correlated with residual pine basal area
      and soil variables related to drainage (e.g., sand concentration, available water
      capacity). Although plant composition was dominated by widespread colonizers such
      as Erechtites hieraciifolia, the coefficient of conservatism (indicative of
      species of more intact, undisturbed communities) significantly increased on
      thinned plots from year 1 to 3. This finding, coupled with the presence of four
      rare, state-listed Ohio species whose eight plot occurrences all were on thinned
      plots, suggests that plant composition is moving towards species typifying more
      high-quality savanna and prairie habitats.

PMID- 20680629
TI  - Expansion or extinction: deterministic and stochastic two-patch models with Allee
      effects.
AB  - We investigate the impact of Allee effect and dispersal on the long-term
      evolution of a population in a patchy environment. Our main focus is on whether a
      population already established in one patch either successfully invades an
      adjacent empty patch or undergoes a global extinction. Our study is based on the
      combination of analytical and numerical results for both a deterministic two
      patch model and a stochastic counterpart. The deterministic model has either two,
      three or four attractors. The existence of a regime with exactly three attractors
      only appears when patches have distinct Allee thresholds. In the presence of weak
      dispersal, the analysis of the deterministic model shows that a high-density and
      a low-density populations can coexist at equilibrium in nearby patches, whereas
      the analysis of the stochastic model indicates that this equilibrium is
      metastable, thus leading after a large random time to either a global expansion
      or a global extinction. Up to some critical dispersal, increasing the intensity
      of the interactions leads to an increase of both the basin of attraction of the
      global extinction and the basin of attraction of the global expansion. Above this
      threshold, for both the deterministic and the stochastic models, the patches tend
      to synchronize as the intensity of the dispersal increases. This results in
      either a global expansion or a global extinction. For the deterministic model,
      there are only two attractors, while the stochastic model no longer exhibits a
      metastable behavior. In the presence of strong dispersal, the limiting behavior
      is entirely determined by the value of the Allee thresholds as the global
      population size in the deterministic and the stochastic models evolves as
      dictated by their single-patch counterparts. For all values of the dispersal
      parameter, Allee effects promote global extinction in terms of an expansion of
      the basin of attraction of the extinction equilibrium for the deterministic model
      and an increase of the probability of extinction for the stochastic model.

PMID- 20680630
TI  - A patient with swelling of the eyelid: ancient schwannoma of the supraorbital
      nerve (2010:6b).
AB  - We present a case of swelling of the eyelid and supraorbital anesthesia caused by
      an intraorbital tumor. The differential diagnosis based on imaging consisted of
      aneurysmal bone cyst, schwannoma, neurofibroma, dermoid cyst, and cavernous
      hemangioma. The surgical and pathological diagnosis was an ancient schwannoma of
      the orbit, a rare entity.

PMID- 20680633
TI  - Spigelian-cryptorchidism syndrome: a case report and discussion of the basic
      elements in a possibly new congenital syndrome.
AB  - Pediatric cases of Spigelian hernias are rare. Only a few reports on this
      condition, in combination with ipsilateral cryptorchidism and testis in the
      hernia sac, have been published. We report on Spigelian hernia in a 3-week-old
      boy containing both the ipsilateral testis, without a gubernaculum and an
      incarcerated loop of the small intestine. It has been suggested that the
      combination of Spigelian hernia and ipsilateral cryptorchidism is part of a new
      syndrome. We discuss whether the lack of a gubernaculum and an inguinal canal
      reported in other similar cases may be additional elements of this new syndrome.
      We present a comprehensive overview of pediatric patients with Spigelian
      cryptorchidism syndrome reported in the English language literature. In 75% of
      male infants with Spigelian hernia, there is an associated ipsilateral
      cryptorchidism, and in 87% of these patients, the testis is found inside the
      hernia sac. Thus, the surgeon dealing with a congenital Spigelian hernia should
      look for an undescended testis and be prepared to find it in the hernia sac.

PMID- 20680632
TI  - Pheromones and signature mixtures: defining species-wide signals and variable
      cues for identity in both invertebrates and vertebrates.
AB  - Pheromones have been found in species in almost every part of the animal kingdom,
      including mammals. Pheromones (a molecule or defined combination of molecules)
      are species-wide signals which elicit innate responses (though responses can be
      conditional on development as well as context, experience, and internal state).
      In contrast, signature mixtures, in invertebrates and vertebrates, are variable
      subsets of molecules of an animal's chemical profile which are learnt by other
      animals, allowing them to distinguish individuals or colonies. All signature
      mixtures, and almost all pheromones, whatever the size of molecules, are detected
      by olfaction (as defined by receptor families and glomerular processing), in
      mammals by the main olfactory system or vomeronasal system or both. There is
      convergence on a glomerular organization of olfaction. The processing of all
      signature mixtures, and most pheromones, is combinatorial across a number of
      glomeruli, even for some sex pheromones which appear to have 'labeled lines'.
      Narrowly specific pheromone receptors are found, but are not a prerequisite for a
      molecule to be a pheromone. A small minority of pheromones act directly on target
      tissues (allohormone pheromones) or are detected by non-glomerular
      chemoreceptors, such as taste. The proposed definitions for pheromone and
      signature mixture are based on the heuristic value of separating these kinds of
      chemical information. In contrast to a species-wide pheromone, there is no single
      signature mixture to find, as signature mixtures are a 'receiver-side' phenomenon
      and it is the differences in signature mixtures which allow animals to
      distinguish each other.

PMID- 20680634
TI  - Chylothorax in congenital diaphragmatic hernia.
AB  - PURPOSE: Following surgical repair of congenital diaphragmatic hernia (CDH),
      chylothorax can be present in 7-28% of the cases. It has been associated with
      prenatal diagnosis, the use of ECMO and prosthetic patches during reparatory
      surgery. The objective is to present a neonatal unit experience in handling this
      complication and the search for predictive factors for its appearance in our
      patients. METHODS: A retrospective study was carried out between 2003 and 2009.
      RESULTS: We found 65 patients with CDH, of which 7 (10.8%) developed a
      chylothorax, 5 responded to drainage and diet restriction. Octreotide (OCT) was
      used in two cases that did not respond to the usual treatment. OCT was successful
      with one patient, while surgical resolution of the chylothorax was necessary in
      the other. Two patients died, none of them during treatment of chylothorax. We
      did not find a significant association between chylothorax and the variables
      studied in these patients. CONCLUSIONS: Chylothorax is a common complication
      following CDH repair. We have a low rate of this complication in our institution.
      Conservative management is an appropriate approach for all patients; OCT could be
      an alternative to avoid surgery. We did not find any predictive factors for
      chylothorax in our series.

PMID- 20680635
TI  - EXIT procedure in a neonate with a prenatally diagnosed granular cell tumor.
AB  - Congenital oral tumor masses might cause ventilation problems in the neonate. We
      report the first case of an EXIT procedure performed in a fetal granular cell
      tumor arising from the maxilla that was diagnosed prenatally followed by surgical
      correction on the 4th day of life. The EXIT procedure is an elegant approach to
      optimize perinatal airway management in such tumors.

PMID- 20680636
TI  - Aquaporin-4 astrocytopathy in Balo's disease.
AB  - Balo's concentric sclerosis (BCS) is considered to be a rare variant of multiple
      sclerosis and characterized by alternating rings of demyelinated and preserved
      myelin layers. The mechanism underlying BCS remains to be elucidated. Recently,
      occurrence of concentric rings of Balo was described in the brainstem of a
      patient with neuromyelitis optica (NMO). Because selective loss of aquaporin-4
      (AQP4) and vasculocentric deposition of complement and immunoglobulins are
      characteristic in NMO, we aimed to assess AQP4 expression in the concentric
      demyelinating lesions of BCS patients. We evaluated AQP4 expression relative to
      expression of another astrocytic marker (glial fibrillary acidic protein), the
      extent of demyelination, lesion staging and perivascular deposition of complement
      and immunoglobulin in four cases with BCS, and 30 individuals with other
      neurological diseases. All cases with BCS demonstrated extensive AQP4 loss in
      both demyelinated and myelinated layers of all actively demyelinating lesions,
      with perivascular lymphocytic cuffing of T cells, but no deposition of
      immunoglobulins or complement around vessels. These findings suggest that AQP4
      loss occurs in heterogeneous demyelinating conditions, namely NMO and BCS.
      Furthermore, acute BCS lesions are characterized by extensive AQP4 loss without
      vasculocentric deposition of complement or immunoglobulin.

PMID- 20680637
TI  - High-density areas on muscle CT in childhood-onset Pompe disease are caused by
      excess calcium accumulation.
AB  - We report two patients with childhood-onset Pompe disease showing striking
      changes with high-density areas on skeletal muscle CT, not seen in adult- or
      infantile-onset forms of this disease. While the anterior compartment of the
      thigh muscles was less affected in the adult-onset form, the rectus femoris and
      tibial muscles were preferentially involved from the early stage in the childhood
      onset form of Pompe disease. The high-density areas became increasingly diffuse
      with disease progression, producing a marbled pattern and ultimately resulting in
      homogeneous high density and muscle atrophy. Muscle biopsy specimens from the
      high-density areas showed striking vacuolar changes with many dense globular
      bodies in lysosomes. High calcium signals were identified by X-ray microanalysis
      using energy-dispersive X-ray spectroscopy in these areas. Excess calcium
      accumulation in the vacuoles was also confirmed with the glyoxal-bis(2
      hydroxyanil) (GBHA) staining. The high density on CT was slightly reduced
      together with clinical improvement after enzyme replacement therapy in patient 2.
      Our data demonstrate that in childhood-onset Pompe disease, high-density areas on
      skeletal muscle CT images are due to the accumulation of calcium in dense
      globular bodies formed by a chronic degenerative process affecting autophagic
      vacuoles.

PMID- 20680638
TI  - Posterior fossa metastasis in lung cancer patients with vertigo.
AB  - This study investigated whether vertiginous attacks indicate a high probability
      for posterior fossa metastasis in lung cancer patients. Twenty-five lung cancer
      patients having vertiginous episodes were enrolled in this study. All patients
      underwent a battery of audiovestibular function testing and MR imaging study. Ten
      (40%) of 25 lung cancer patients with vertigo were proven to have posterior fossa
      metastasis (PM1 group), while the other 15 patients had no posterior fossa
      metastasis (PM0 group). Of the PM1 group, all were adenocarcinoma with the women
      predominant (80%). Seven (70%) and two (13%) patients of PM1 and PM0 groups had
      other (bone, liver) systemic metastases before the vertigo episodes,
      respectively, exhibiting significant difference between them. However, no
      statistical differences existed in the audiovestibular function testing between
      the two groups. In contrast with 58% of PM0 group, none of the patients in PM1
      group survived for > 3 years after the vertiginous attacks. The mean interval
      from vertiginous episode to death was 16 months (range 5-27). In conclusion,
      vertiginous attack in a lung cancer patient having other systemic metastases
      indicates a high probability of posterior fossa metastasis.

PMID- 20680639
TI  - Management of petrous bone cholesteatoma: open versus obliterative techniques.
AB  - The objective of this study was to expose our results in the treatment of petrous
      bone cholesteatomas (PBC), paying attention to diagnosis, surgical strategy,
      facial management, results, and recurrences. The main objective is to compare the
      results of obliterative and open techniques in their management concerning the
      recurrence rate, due to the controversy elicited on obliterative or closed
      techniques in large cholesteatomas. A retrospective study was performed from July
      1977 to September 2007 at the Tertiary referral cranial base center. Thirty-five
      patients were treated for PBC through different surgical approaches, and in 25
      cases (72%) the surgical cavity was obliterated with a muscle flap. Four patients
      (11%) had a long-term recurrence. These patients received an open technique and
      after surgical re-exploration using a closed technique they had no recurrence.
      There were no recurrences in patients who underwent an obliterative technique and
      they received periodic MRI controls. The facial function after surgery was
      acceptable (71% of patients had House-Brackmann grades I to III). PBC is a
      complex pathology and presents difficulties in its diagnosis and treatment.
      Surgical technique should be suitable for removing the pathology and preventing
      damage to structures such as the facial nerve or great vessels. Obliterative
      techniques, where possible, are at least as safe as open cavity procedures and
      they have fewer postoperative complications; however, regular follow-up with CT
      and MRI is mandatory.

PMID- 20680640
TI  - Is there a correlation between 18F-FDG-PET standardized uptake value, T
      classification, histological grading and the anatomic subsites in newly diagnosed
      squamous cell carcinoma of the head and neck?
AB  - (18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography
      (PET)/CT imaging of squamous cell carcinoma of the head and neck (HNSCC) renders
      the possibility to study metabolic tumor activity by measuring FDG-uptake
      expressed as maximum standardized uptake value (SUV(max)). A correlation between
      SUV(max) and several factors including T-classification, histological tumor
      differentiation or different anatomic subsites is of potential interest in HNSCC.
      The aim of this study was to evaluate how metabolic tumor activity derived from
      FDG-PET correlates with prognostic clinical and pathological parameters including
      these factors. 262 patients with HNSCC undergoing PET/CT for initial staging were
      assessed separately for a potential correlation between SUV(max) and T
      classification, histological grading, and anatomical subsites of the primary
      tumor. Nonparametric testing showed a significant correlation between SUV(max)
      and T-classification (P < 0.001). On the contrary, no statistically significant
      correlation was found between SUV(max) and histological tumor grading.
      Furthermore, no statistical significant correlation between the different
      anatomical subsites and SUV(max) were found. There was no significant correlation
      of SUV(max) and tumor grading after adjustment for T-stage and anatomical
      localization of the tumor, neither. CONCLUSION: Metabolic tumor activity
      correlates with T-stage of HNSCC. However, histological tumor grading does not
      correlate with SUV(max). The role of primary tumor SUV(max) as a predictor of
      outcome or survival remains unclear. Clinicians should therefore exercise caution
      in attributing any clinical importance to SUV(max) obtained from a single PET/CT
      exam.

PMID- 20680641
TI  - A disposable system for rapid purification of autologous plasmin as an adjunct to
      vitrectomy - performance and safety profile.
AB  - BACKGROUND: The generation of an atraumatic posterior vitreous detachment (PVD),
      a common goal in vitreoretinal surgery, is a challenge particularly in children
      and young trauma patients. Plasmin has been proposed as a surgical adjunct to
      enzymatically generate a PVD. This study assesses the performance and safety of a
      new system for rapid purification of plasmin as an adjunct to vitrectomy.
      METHODS: Plasminogen was isolated from human plasma by affinity chromatography
      using a disposable rapid purification kit, and activated to plasmin with
      streptokinase. Activities were assessed spectrophotometrically. For safety
      studies, 38 rabbits received intravitreal injections of one of the following
      compounds in 0.1 ml respectively: 4.7, 12.7 and 24 IU plasmin, 15 mg dextran,
      4,100 U streptokinase, 500 MUg epsilon-aminocaproic acid, 0.1 M potassium
      phosphate or balanced salt solution (BSS). Thirty min after injection, a two-port
      vitrectomy was performed. Rabbits were followed clinically and with bright flash
      electroretinography (ERG) for up to 9 months. The eyes were investigated by light
      and transmission electron microscopy. RESULTS: The specific plasmin activity
      obtained from blood of healthy volunteers averaged 42.3 +/- 6.6 IU/ml (range 21.6
      IU/ml to 54.5 IU/ml). The identity and purity of the enzyme was confirmed by
      several methods. Clinically, a mild to moderate inflammatory response was seen in
      most eyes on day 1, but had disappeared by day 7. ERG showed moderate depressions
      of a- and b-wave amplitudes on day 2, particularly in the potassium phosphate (a:
      -29.16 +/- 4.56, b: -21.23 +/- 6.31), 4.7 (a: -34.38 +/- 6.64, b: -26.66 +/-
      6.06) and 24 IU (a: -38.25 +/- 4.05, b: -23.38 +/- 4.29) plasmin groups, but also
      in the BSS- (a: -11.19 +/- 21.78, b: -11.41 +/- 15.47) and dextran- (a: -17.86 +/
      14.18, b: -6.67 +/- 18.14) treated eyes. ERG changes recovered during follow-up.
      One rabbit each from the 12.7 and the 24 IU plasmin groups showed a minimal
      discoloration of one medullary ray after 9 months. Histology did not reveal
      morphologic signs of toxicity. CONCLUSION: The isolation system generated plasmin
      with a high degree of purity. A failure-mode analysis did not reveal significant
      risks of toxicity. A single preparation can provide a maximum dose of 10.9 IU/200
      MUl, the likely target clinical dose being 1.88 IU. Plasmin doses of at least
      12.7 IU appear be safe when injected into rabbit eyes, followed by vitrectomy.

PMID- 20680642
TI  - Decreased ROS level and activation of antioxidant gene expression in
      Agrobacterium rhizogenes pRiA4-transformed calli of Rubia cordifolia.
AB  - Microbe-plant interactions often lead to a decrease in the reactive oxygen
      species (ROS) level of plant cells, which allows pathogen survival through the
      suppression of plant immune responses. In the present investigation, we tested
      whether transformation of Rubia cordifolia cells by Agrobacterium rhizogenes had
      a similar effect. We isolated partial cDNA sequences of ascorbate peroxidase,
      catalase and Cu/Zn superoxide dismutase genes (RcApx1, RcApx2, RcApx3, RcCAT1,
      RcCAT2, RcCSD1, RcCSD2 and RcCSD3) from plant tissues, as well as pRiA4
      transformed and normal calli of Rubia cordifolia, and studied their expression by
      real-time PCR. Transcription profiling revealed that ascorbate peroxidase
      (RcApx1) and Cu/Zn superoxide dismutase (RcCSD1) were the most abundant
      transcripts present in both plant tissues and non-transformed calli. Catalase
      genes were weakly expressed in these samples. The pRiA4-transformed calli showed
      enhanced expression of several genes encoding ROS-detoxifying enzymes. Confocal
      microscopy imaging revealed decreased ROS level in pRiA4-transformed calli
      compared to the control. These results demonstrate that A. rhizogenes, like other
      plant pathogens, uses a strategy aimed at decreasing ROS levels in host cells
      through the general upregulation of its antioxidant genes.

PMID- 20680643
TI  - Identification of metastasis-associated breast cancer genes using a high
      resolution whole genome profiling approach.
AB  - PURPOSE: We employed a whole genome tumor profiling approach in an attempt to
      identify DNA copy number alterations (CNAs) and new candidate genes that are
      correlated with the metastatic potential of a primary breast carcinoma and with
      progression at the metastatic site. METHODS: Fifty-four small (<= 2 cm), high
      grade, ER-positive, formalin-fixed invasive ductal carcinomas were suitable for
      whole genome profiling analysis. Twenty-four of them did not form metastases
      within 5-10 years (unmatched primaries, UP). Thirty tumors had at least one
      synchronous axillary lymph node metastasis (matched primaries, MP; matched lymph
      node metastases, ML). Genomic DNA was hybridized to high density (19k) BAC
      arrays. Statistical analysis revealed differential distributions of CNAs between
      UP and MP and between MP and ML, respectively. We selected 27 candidate genes for
      validation experiments using quantitative (Q-)PCR of genomic DNA. For tetraspanin
      TSPAN1, we studied mRNA expression levels in a separate cohort of primary breast
      carcinomas and in breast cell lines. RESULTS: Matched primary (MP) tumors had a
      threefold higher rate of DNA copy number losses compared to UP tumors. In the UP
      MP comparison, 186 BACs were differentially amplified or deleted. Most of them
      were localized to chromosomes 7p, 16q and 18q. In the MP-ML comparison, 131 BACs
      showed differential CNAs. Most of them were localized to chromosomes 1q and 20.
      By Q-PCR, seven candidate genes could be confirmed to show differential
      distributions of CNAs. TSPAN1 was amplified in UP and deleted in MP tumors. The
      gene was markedly downregulated in ER-negative and high-grade breast cancers.
      CONCLUSIONS: Metastasizing tumors had a higher rate of deletions, suggesting
      possible inactivation of metastasis suppressor genes. We provide preliminary
      evidence that TSPAN1 may be another important breast cancer suppressor gene
      belonging to the tetraspanin superfamily.

PMID- 20680644
TI  - Intraspecific variation in allelochemistry determines an invasive species' impact
      on soil microbial communities.
AB  - Invasive species can benefit from altered species interactions in their new
      range, and by interfering with species interactions among native competitors.
      Since exotic invasions are generally studied at the species level, relatively
      little is known about intraspecific variation in the traits that determine an
      invader's effect on native species. Alliaria petiolata is a widespread and
      aggressive invader of forest understories that succeeds in part by interfering
      with mutualistic interactions between native plants and soil fungi. Here, I show
      that the impact of A. petiolata on soil microbial communities varied among
      individuals due to variation in their allelochemical concentrations. The
      differential impacts translated into varied effects on native tree growth, partly
      because A. petiolata's allelochemicals preferentially affected the most
      mutualistic fungal taxa. These results highlight the importance of considering
      the spatial and temporal variation in an invasive species' impacts for
      understanding and managing the invasion process.

PMID- 20680645
TI  - Legume species differ in the responses of their functional traits to plant
      diversity.
AB  - Plants can respond to environmental impacts by variation in functional traits,
      thereby increasing their performance relative to neighbors. We hypothesized that
      trait adjustment should also occur in response to influences of the biotic
      environment, in particular different plant diversity of the community. We used 12
      legume species as a model and assessed their variation in morphological,
      physiological, life-history and performance traits in experimental grasslands of
      different plant species (1, 2, 4, 8, 16 and 60) and functional group (1-4)
      numbers. Mean trait values and their variation in response to plant diversity
      varied among legume species and from trait to trait. The tall-growing Onobrychis
      viciifolia showed little trait variation in response to increasing plant
      diversity, whereas the species with shorter statures responded in apparently
      adaptive ways. The formation of longer shoots with elongated internodes,
      increased biomass allocation to supporting tissue at the cost of leaf mass,
      reduced branching, higher specific leaf areas and lower foliar delta(13)C values
      indicated increasing efforts for light acquisition in more diverse communities.
      Although leaf nitrogen concentrations and shoot biomass:nitrogen ratios were not
      affected by increasing plant diversity, foliar delta(15)N values of most legumes
      decreased and the application of the (15)N natural abundance method suggested
      that they became more reliant on symbiotic N(2) fixation. Some species formed
      fewer inflorescences and delayed flowering with increasing community diversity.
      The observed variation in functional traits generally indicated strategies of
      legumes to optimize light and nutrient capturing, but they were largely species
      dependent and only partly attributable to increasing canopy height and community
      biomass with increasing plant diversity. Thus, the analysis of individual plant
      species and their adjustment to growth conditions in communities of increasing
      plant diversity is essential to get a deeper insight into the mechanisms behind
      biodiversity-ecosystem functioning relationships.

PMID- 20680646
TI  - Feeding on poplar leaves by caterpillars potentiates foliar peroxidase action in
      their guts and increases plant resistance.
AB  - Peroxidases (PODs) are believed to act as induced and constitutive defenses in
      plants against leaf-feeding insects. However, little work has examined the mode
      of action of PODs against insects. Putative mechanisms include the production of
      potentially antinutritive and/or toxic semiquinone free radicals and quinones
      (from the oxidation of phenolics), as well as increased leaf toughness. In this
      study, transgenic hybrid poplar saplings (Populus tremula * Populus alba)
      overexpressing horseradish peroxidase (HRP) were produced to examine the impact
      of elevated HRP levels on the performance and gut biochemistry of Lymantria
      dispar caterpillars. HRP-overexpressing poplars were more resistant to L. dispar
      than wild-type (WT) poplars when the level of a phenolic substrate of HRP
      (chlorogenic acid) was increased, but only when leaves had prior feeding damage.
      Damaged (induced) leaves produced increased amounts of hydrogen peroxide, which
      was used by HRP to increase the production of semiquinone radicals in the midguts
      of larvae. The decreased growth rates of larvae that fed on induced HRP
      overexpressing poplars resulted from post-ingestive mechanisms, consistent with
      the action of HRP in their midguts. The toughness of HRP-overexpressing leaves
      was not significantly greater than that of WT leaves, whether or not they were
      induced. When leaves were coated with ellagitannins, induced HRP leaves also
      produced elevated levels of semiquinone radicals in the midgut. Decreased larval
      performance on induced HRP leaves in this case was due to post-ingestive
      mechanisms as well as decreased consumption. The results of this study provide
      the first demonstration that a POD is able to oxidize phenolics within an insect
      herbivore's gut, and further clarifies the chemical conditions that must be
      present for PODs to function as antiherbivore defenses.

PMID- 20680647
TI  - [Reference values for quantitative sensory testing in children and adolescents :
      Developmental and gender differences in somatosensory perception].

PMID- 20680649
TI  - Towards improving the safety and diagnostic yield of stereotactic biopsy in a
      single centre.
AB  - BACKGROUND: Previously, we reported on our single centre results regarding the
      diagnostic yield of stereotactic needle biopsies of brain lesions. The yield then
      (1996-2006) was 89.4%. In the present study, we review and evaluate our
      experience with intraoperative frozen-section histopathologic diagnosis on-demand
      in order to improve the diagnostic yield. METHODS: One hundred sixty-four
      consecutive frameless biopsy procedures in 160 patients (group 1, 2006-2010) were
      compared with the historic control group (group 2, n = 164 frameless biopsy
      procedures). Diagnostic yield, as well as demographics, morbidity and mortality,
      was compared. Statistical analysis was performed by Student's t, Mann-Whitney U,
      Chi-square test and backward logistic regression when appropriate. RESULTS:
      Demographics were comparable. In group 1, a non-diagnostic tissue specimen was
      obtained in 1.8%, compared to 11.0% in group 2 (p = 0.001). Also, both the
      operating time and the number of biopsies needed were decreased significantly.
      Procedure-related mortality decreased from 3.7% to 0.6% (p = 0.121). Multivariate
      analysis only proved operating time (odds ratio (OR), 1.012; 95% confidence
      interval (CI), 1.000-1.025; p = 0.043), a right-sided lesion (OR, 3.183; 95% CI,
      1.217-8.322; p = 0.018) and on-demand intraoperative histology (OR, 0.175; 95%
      CI, 0.050-0.618; p = 0.007) important factors predicting non-diagnostic biopsies.
      CONCLUSIONS: The importance of a reliable pathological diagnosis as obtained by
      biopsy must not be underestimated. We believe that when performing stereotactic
      biopsy for intracranial lesions, next to minimising morbidity, one should strive
      for as high a positive yield as possible. In the present single centre
      retrospective series, we have shown that using a standardised procedure and
      careful on-demand intraoperative frozen-section analysis can improve the
      diagnostic yield of stereotactic brain biopsy procedures as compared to a
      historical series.

PMID- 20680650
TI  - Hyponatremia is predictable in patients with aneurysmal subarachnoid hemorrhage-
      clinical significance of serum atrial natriuretic peptide.
AB  - PURPOSE: Serum atrial natriuretic peptide (ANP) that is elevated after aneurysmal
      subarachnoid hemorrhage (SAH) causes diuresis and natriuresis (cerebral salt
      wasting) and might exacerbate delayed ischemic neurological deficit (DIND). We
      investigated relationships among hyponatremia, serum ANP elevation, and the onset
      of DIND after SAH. MATERIALS AND METHODS: Thirty-nine consecutive patients (15
      women and 24 men) with SAH were assigned to a normonatremia group or a group that
      developed hyponatremia after SAH. Serum ANP and brain natriuretic peptide were
      assessed after SAH. All patients remained normovolemic and normotensive. We
      attributed DIND to vasospasm only in the absence of other causes and when
      supported by cerebral angiography. RESULTS: Hyponatremia developed after SAH in
      11 patients (28.2%), among whom serum ANP concentrations at 0 and 3 days
      thereafter were significantly increased. Furthermore, DIND developed in five
      (45.5%) and two (7.1%) hyponatremic and normonatremic patients, respectively (P <
      0.05). The serum ANP levels on day 0 after SAH were higher in Hunt and Kosnik
      grades 3-4 than in 1-2 and in Fisher groups 3-4 than in 1-2 (P < 0.05).
      CONCLUSIONS: Increasing serum ANP concentrations were independently associated
      with hyponatremia resulting in DIND. Early treatment of hyponatremia might
      prevent DIND in patients after SAH.

PMID- 20680651
TI  - The E2F-1 associated retinoblastoma-susceptibility gene product is modified by O
      GlcNAc.
AB  - The retinoblastoma-susceptibility gene product (pRB) is a classical tumor
      suppressor. pRB regulates a number of cellular processes including proliferation,
      differentiation, and apoptosis. One of the essential mechanisms by which pRB, and
      the related p107 and p130 family members, act is through its interactions with
      the E2F class of transcription factors. E2F-1 transcription is necessary for
      entry into S-phase during the cell-cycle. pRB binds E2F-1 and represses
      transcription via recruitment of a histone deacetylase complex and by preventing
      co-activator complexes from binding E2F-1. Current dogma suggests that
      phosphorylation of pRB during mid- to late-G1 leads to release of E2F-1 and E2F-1
      dependent transcriptional activation of essential S-phase genes. Here we show
      that pRB, and the related p107 protein, are modified by O-linked beta-N
      acetylglucosamine (O-GlcNAc) in an in vitro transcription/translation system.
      Furthermore, we show in vivo that pRB is more heavily glycosylated in G1 of the
      cell-cycle when pRB is known to be in an active, hypophosphorylated state.
      Finally, we demonstrate that E2F-1 associated pRB is modified by O-GlcNAc. These
      studies suggest that regulation of pRB function(s) may be controlled by dynamic O
      GlcNAc modification, as well as phosphorylation.

PMID- 20680652
TI  - OCT1 polymorphism is associated with response and survival time in anti
      Parkinsonian drug users.
AB  - Substrates for the Organic Cation Transporter 1, encoded by the SLC22A1 gene, are
      metformin, amantadine, pramipexole, and, possibly, levodopa. Recently, we
      identified that the rs622342 A > C polymorphism is associated with the HbA1c
      lowering effect in metformin users. In the Rotterdam Study, we associated this
      polymorphism with higher prescribed doses of all anti-Parkinsonian drugs. Between
      the first and fifth prescriptions for levodopa, for each minor rs622342 C allele,
      the prescribed doses were 0.34 defined daily dose higher (95% CI 0.064, 0.62;
      p=0.017). The mortality ratio after start of levodopa therapy was 1.47 times
      higher (95% CI 1.01, 2.13; p=0.045).

PMID- 20680653
TI  - Benefit of follow-up CT in emergency department patients with persistent non
      traumatic abdominal pain.
AB  - To determine the benefit of a short-term follow-up abdominopelvic computed
      tomography (APCT) examination among emergency department (ED) patients with
      persistent abdominal pain and an initially negative CT. During a 5-year period
      from January 2004 to December 2008, our institution's radiology department
      performed approximately 56,000 APCTs examinations in the ED. Sixty-eight percent
      of the APCT examinations used intravenous contrast. Nine hundred fifty-seven
      patients received two APCTs within 1 week for non-traumatic abdominal pain in the
      ED. Sixty-four patients with initially negative APCTs presented to the ED within
      1 week with persistent abdominal pain and received follow-up APCT imaging. The
      mean follow-up period was 2.6 days. The mean interval period in which the second
      APCT yielded a positive result was 2.0 days. Seventy-five percent of follow-up
      examinations were performed with intravenous contrast. Twenty-three percent of
      patients had positive findings on the follow-up examination. Seventy-three
      percent of the follow-up positive findings were referable to bowel pathology. The
      cause of abdominal pain remained elusive at 1 week in 23% of patients. Short-term
      follow-up APCT examinations in patients with persistent, unexplained abdominal
      pain may be of benefit if the second APCT is performed with intravenous contrast
      in patients suspected of having bowel pathology.

PMID- 20680654
TI  - Exploring the relationship between costs and quality: does the joint evaluation
      of costs and quality alter the ranking of Danish hospital departments?
AB  - OBJECTIVE: The purpose is to evaluate the relationship between costs and quality
      and to assess whether the joint evaluation of costs and quality affects the
      ranking of hospital departments relative to comparison based on costs alone.
      METHODS: Using patient level data for 3,754 patients in six vascular departments,
      we estimate fixed effect models for costs (linear) and quality (logistic). We
      consider two quality measures; mortality and wound complications. To assess
      whether the joint evaluation of costs and quality affects the ranking of
      departments, we construct joint confidence regions for each pair of departmental
      effects for costs and quality using a bootstrap method and rank departments
      according to their cost-effectiveness ratio. The findings are used to evaluate a
      theory of a U-shaped cost/quality relationship. RESULTS: The association between
      cost and quality differs depending on how quality is measured. Lower costs are
      associated with higher mortality, implying a cost/quality trade-off. In contrast,
      there is no clear association between costs and wound complications among
      vascular departments. CONCLUSIONS: Compared to benchmarking of departments based
      solely on their costs, we show that the ranking of departments may be altered
      considerably when quality is taken into account. Consequently, it is important to
      have a well-rounded view of departmental objectives when undertaking performance
      evaluation. The results for mortality may lend some support to the theory of a U
      shaped cost/quality relationship. However, the results for wound complications do
      not support the theory of a U-shaped cost/quality relationship.

PMID- 20680655
TI  - Quality of life among an Iranian general population sample using the World Health
      Organization's quality of life instrument (WHOQOL-BREF).
AB  - OBJECTIVES: To assess subjective quality of life of an Iranian general population
      sample. METHODS: This was a population-based study. Quality of life was measured
      using the WHOQOL-BREF. The associations between socio-demographic variables and
      quality of life were assessed by both univariate and multivariate analyses.
      RESULTS: In all, 1,164 individuals were studied. The mean age of the participants
      was 37.6 (SD = 13.2) years, and the mean score for quality of life domains
      (physical, psychological, social relationship and environment domains) was 14.3
      (SD = 2.6), 13.4 (SD = 2.6), 13.9 (SD = 2.6), and 12.3 (SD = 2.4), respectively.
      The results obtained from univariate analysis did not show a consistent pattern
      for association between demographic variables and quality of life domains.
      However, multivariate regression analysis showed that self-reported health
      condition was the most significant contributing factor to the decreased scores
      for all domains. CONCLUSIONS: Overall, quality of life scores were found to be
      low among an Iranian general population and greatly varied by socio-demographic
      variables. In addition, self-reported health condition was found to be the
      strongest factor affecting people's quality of life.

PMID- 20680656
TI  - Married men who have sex with men: the bridge to HIV prevention in Mumbai, India.
AB  - OBJECTIVES: The present study compared the sexual behaviours of married and
      unmarried men, in Mumbai, India, who have sex with men. METHODS: We conducted a
      cross-sectional analysis (comparing socio-demographic, behavioural and clinical
      data) of 88 married and 423 unmarried MSM. RESULTS: Even though MSM are single at
      younger ages, they are more likely to be married later in life and carry their
      risky sexual behaviours to this changed social milieu. CONCLUSIONS: Married MSM
      had high-risk behaviours with both men and women; they form an important
      intervention group for HIV prevention. The interventions will not only reduce the
      transmission in the male-to-male sexual group, but will also have an effect on
      the male-to-female transmission of HIV.

PMID- 20680657
TI  - Using risk factor surveillance as a basis for mixed-methodology research: an
      example from Australia using food intake and anthropometric measures.
AB  - OBJECTIVES: Risk factor surveillance is an integral part of public health, and
      can provide a ready-made sample for further research. This study assessed the
      utility of mixed-methodology research using telephone and postal surveys.
      METHODS: Adult respondents to telephone surveys in South Australia and Western
      Australia were recruited to a postal survey about food consumption, in
      particular, relating to fruit and vegetables. Responses to the two surveys were
      compared. RESULTS: Around 60% of eligible telephone survey respondents
      participated in the postal survey. There was fair to poor agreement between the
      results from the two methods for serves of fruit and vegetables consumed. There
      was excellent agreement between the two methods for self-reported height and
      weight. CONCLUSIONS: The telephone survey was a useful way to recruit people to
      the postal survey; this could be due to the high level of trust gained through
      the telephone interview, or social desirability bias. It is difficult to
      ascertain why different results on fruit and vegetable intake were obtained, but
      it may be associated with understanding of the parameters of a 'serve', recall
      bias or the time taken to calculate an answer.

PMID- 20680658
TI  - Closing the gap in a generation: what more research do we need?

PMID- 20680659
TI  - Histone deacetylase inhibitors enhance the anticancer activity of nutlin-3 and
      induce p53 hyperacetylation and downregulation of MDM2 and MDM4 gene expression.
AB  - Nutlin-3, a small-molecule MDM2 inhibitor, restores p53 function and is, thus, an
      appealing candidate for the treatment of cancers retaining wild-type p53.
      However, nutlin-3 applied as single agent may be insufficient for cancer therapy.
      Therefore, we explored whether the anticancer activity of nutlin-3 could be
      enhanced by combination with histone deacetylase inhibitors (HDACi), i.e.
      vorinostat, sodium butyrate, MS-275 and apicidin. We found that nutlin-3 and
      HDACi cooperated to induce cell death in the p53 wild-type cell lines A549 and
      A2780, but not in the p53 null cell line PC-3, as assessed by Alamar Blue assay
      and flow cytometric analyses of propidium iodide uptake and mitochondrial
      depolarization. Combination index analysis showed that the effect was
      synergistic. For comparison, we tested nutlin-3 in combination with paclitaxel,
      revealing that nutlin-3 antagonized the cytotoxic activity of paclitaxel. To shed
      light on the underlying mechanism of the synergistic action of nutlin-3 and
      HDACi, we determined the acetylation status of p53 by immunoblotting and the mRNA
      levels of MDM2 and MDM4 by real-time RT-PCR. We observed vorinostat to induce p53
      hyperacetylation, to reduce the constitutive gene expression of MDM2 and MDM4,
      and to counteract the nutlin-3-induced upregulation of MDM2 gene expression. In
      conclusion, our study shows that HDACi amplify the antitumor activity of nutlin-3
      possibly by inducing p53 hyperacetylation and/or MDM2 and/or MDM4 downregulation
      suggesting that treatment with a combination of nutlin-3 and HDACi may be an
      effective strategy for treating tumors with wild-type p53.

PMID- 20680661
TI  - Selective observation of the Cu(I)-amicyanin metal site by paramagnetic NMR on
      partially oxidised samples.
AB  - The relaxation enhancement caused by paramagnetic copper(II) is used to observe
      selectivelythe metal site of copper(I)-amicyanin by one- and two-dimensional NMR
      spectroscopy. Theparamagnetic effect is communicated to the diamagnetic protein
      through the electron self-exchange reaction in partially oxidised samples, and
      can be used for the selective detectionof protons around the metal. Relaxation
      selective NMR pulse sequences, like super-WEFTand WEFT-NOESY, are used to achieve
      the desired selection of the signals. The spectraobtained show well-resolved
      signals corresponding to protons within a radius of approximately 7 A from the
      metal, including almost all protons from the coordinated residues. A significant
      increasein resolution as well as selection of the most relevant part of the
      protein (close to the activecentre) are the principal advantages of this
      technique, which can be used to obtain specificinformation about the metal site
      in blue copper proteins, to assist in the assignment of theirNMR spectra and to
      determine functional properties like the electron self-exchange rate.

PMID- 20680660
TI  - A phase 1 study of BMS-275183, a novel oral analogue of paclitaxel given on a
      daily schedule to patients with advanced malignancies.
AB  - PURPOSE: BMS-275183 is an oral C-4 methyl carbonate analogue of paclitaxel that
      has the same mechanism of action, stabilization of tubulin polymerization. The
      present study was designed to: (i) assess the safety and tolerability of BMS
      275183, and (ii) determine a suitable Phase II dose of BMS-275183 when given on a
      continuous daily schedule to patients with advanced solid tumor(s). METHODS: This
      was a multi-institutional, open-label, Phase I, single-arm dose escalation study
      in which cohorts of eligible patients with advanced malignancies were treated
      with BMS-275183 orally on a continuous daily schedule. The starting dose level
      was 6 mg/m(2)/day administered once daily. Cohorts of 3 patients were treated at
      each dose level provided no dose-limiting toxicities (DLTs) were observed. Each
      cycle of treatment lasted 28 days. RESULTS: Twenty patients were enrolled in dose
      cohorts ranging from the initial dose level of 6 mg/m(2)/day to 18 mg/m(2)/day.
      Overall, the most frequent (>20% of patients) treatment-related adverse events
      (AEs) were nausea (40%), constipation (20%), diarrhea (20%), and fatigue (20%).
      There were 2 fatal events of neutropenic sepsis one each at the 15 mg/m(2)/day
      and 18 mg/m(2)/day dose level, respectively. There were no objective responses; 4
      of 20 patients experienced stable disease. Pharmacokinetic data indicated no
      clear correlation between dose and exposure following daily oral administration
      of BMS-275183 doses between 6 and 18 mg/m(2). Substantial inter-patient
      variability was observed, and high drug exposure was associated with fatal
      neutropenic sepsis. CONCLUSIONS: BMS-275183 is a novel oral analogue of
      paclitaxel with high inter-patient variability in exposure. The lack of evidence
      of clinical benefit and the occurrence of two fatal events of neutropenic sepsis,
      coupled with high drug exposure, argues against further evaluation of BMS-275183
      on a daily dosing schedule.

PMID- 20680662
TI  - Stereospecific assignment of the NH2 resonances from the primary amides of
      asparagine and glutamine side chains in isotopically labeled proteins.
AB  - An HMQC-based pulse scheme is presented for the stereospecific assignment of
      asparagineand glutamine side-chain amide protons. The approach makes use of the
      recently developedquantitative-J correlation spectroscopy [Bax, A. et al. (1994)
      Methods Enzymol., 239,79-105] to distinguish the E and Z primary amide protons
      and, as such, eliminates theneed for assignments derived from more time-consuming
      and potentially ambiguous NOEmethods. An application of this method to a
      uniformly 15N,13C-labeled cellulose-bindingdomain is presented. When used in
      combination with a NOESY-HSQC experiment, thepredominant chi2 dihedral angles of
      two asparagine side chains in this protein can also bedefined.

PMID- 20680663
TI  - A 15n-filtered 2D 1H TOCSY experiment for assignment of aromatic ring resonances
      and selective identification of tyrosine ring resonances in proteins: Description
      and application to Photoactive Yellow Protein.
AB  - A new method to selectively detect the ring resonances of the aromatic residues
      in 15N-labelled proteins is presented. The experiment consists of a 2D 1H TOCSY
      sequence withremoval of the amide signals via 15N-filtering. Experiments are
      acquired in the absence andpresence of water inversion; combining the two spectra
      allows selective observation of thetyrosine ring resonances and enables the
      identification of their delta andepsilon ring protons. The experiment is
      demonstrated on a 15N-labelled sample of Photoactive Yellow Protein and isshown
      to give good selectivity for tyrosine ring resonances under a wide range
      oftemperatures and pH values.

PMID- 20680664
TI  - Structural characteristic, pH and thermal stabilities of apo and holo forms of
      caprine and bovine lactoferrins.
AB  - Apo and holo forms of lactoferrin (LF) from caprine and bovine species have been
      characterized and compared with regard to the structural stability determined by
      thermal denaturation temperature values (T (m)), at pH 2.0-8.0. The bovine
      lactoferrin (bLF) showed highest thermal stability with a T (m) of 90 +/- 1
      degrees C at pH 7.0 whereas caprine lactoferrin (cLF) showed a lower T (m) value
      68 +/- 1 degrees C. The holo form was much more stable than the apo form for the
      bLF as compared to cLF. When pH was gradually reduced to 3.0, the T (m) values of
      both holo bLF and holo cLF were reduced showing T (m) values of 49 +/- 1 and 40
      +/- 1 degrees C, respectively. Both apo and holo forms of cLF and bLF were found
      to be most stable at pH 7.0. A significant loss in the iron content of both holo
      and apo forms of the cLF and bLF was observed when pH was decreased from 7.0 to
      2.0. At the same time a gradual unfolding of the apo and holo forms of both cLF
      and bLF was shown by maximum exposure of hydrophobic regions at pH 3.0. This was
      supported with a loss in alpha-helix structure together with an increase in the
      content of unordered (aperiodic) structure, while beta structure seemed unchanged
      at all pH values. Since LF is used today as fortifier in many products, like
      infant formulas and exerts many biological functions in human, the structural
      changes, iron binding and release affected by pH and thermal denaturation
      temperature are important factors to be clarified for more than the bovine
      species.

PMID- 20680665
TI  - In vitro antioxidant and antibacterial properties of hydrolysed proteins of
      delimed tannery fleshings: comparison of acid hydrolysis and fermentation
      methods.
AB  - Proteins in delimed tannery fleshings were fermentatively hydrolysed using
      Enterococcus faecium NCIM5335 and also hydrolysed using mild organic acids
      (formic acid and propionic acid). The liquor portion containing hydrolysed
      proteins was spray dried, in both the cases, to obtain a powder. The spray dried
      powder was evaluated for in vitro antioxidant activities with respect to
      scavenging different free radicals and antibacterial properties against nine
      different pathogens. Fermentation and acid hydrolysates scavenged 83 and 75.3% of
      2,2-azino-bis-3-ethyl-benzthiazoline-6-sulphonic acid (ABTS) radicals,
      respectively, at a protein concentration of 0.25 mg. Further, fermentation
      hydrolysate showed higher 2,2-diphenyl-1-picrylhydrazyl radical scavenging
      activity of 59% as compared to 56% scavenging by acid hydrolysate at a protein
      concentration of 5 mg. Acid hydrolysate exhibited lesser (82.3%) peroxy radical
      scavenging compared to hydrolysate from fermentation (88.2%) at a protein
      concentration of 10 mg. However, acid hydrolysate exhibited higher (89.2%)
      superoxide anion scavenging while its fermentation counterpart showed lower
      activity (85.4%) at 2.5 mg hydrolysate protein. Well as superoxide anion
      scavenging properties. All the in vitro antioxidant properties exhibited dose
      dependency. Fermentation hydrolysate exhibited maximum antagonistic activity
      against Salmonella typhi FB231, from among host of pathogens evaluated. Both the
      hydrolysates have potential to be ingredients in animal feeds and can help reduce
      oxidative stress in the animals.

PMID- 20680666
TI  - Bioaugmentation and biostimulation strategies to improve the effectiveness of
      bioremediation processes.
AB  - Bioremediation, involving bioaugmentation and/or biostimulation, being an
      economical and eco-friendly approach, has emerged as the most advantageous soil
      and water clean-up technique for contaminated sites containing heavy metals
      and/or organic pollutants. Addition of pre-grown microbial cultures to enhance
      the degradation of unwanted compounds (bioaugmentation) and/or injection of
      nutrients and other supplementary components to the native microbial population
      to induce propagation at a hastened rate (biostimulation), are the most common
      approaches for in situ bioremediation of accidental spills and chronically
      contaminated sites worldwide. However, many factors like strain selection,
      microbial ecology, type of contaminant, environmental constraints, as well as
      procedures of culture introduction, may lead to their failure. These drawbacks,
      along with fragmented literature, have opened a gap between laboratory trials and
      on-field application. The present review discusses the effectiveness as well as
      the limitations of bioaugmentation and biostimulation processes. A summary of
      experimental studies both in confined systems under controlled conditions and of
      real case studies in the field is presented. A comparative account between the
      two techniques and also the current scenario worldwide for in situ biotreatment
      using bioaugmentation and biostimulation, are addressed.

PMID- 20680667
TI  - Holmium nanoparticles: preparation and in vitro characterization of a new device
      for radioablation of solid malignancies.
AB  - PURPOSE: The present study introduces the preparation and in vitro
      characterization of a nanoparticle device comprising holmium acetylacetonate for
      radioablation of unresectable solid malignancies. METHODS: HoAcAc nanoparticles
      were prepared by dissolving holmium acetylacetonate in chloroform, followed by
      emulsification in an aqueous solution of a surfactant and evaporation of the
      solvent. The diameter, surface morphology, holmium content, and zeta potential
      were measured, and thermal behavior of the resulting particles was investigated.
      The stability of the particles was tested in HEPES buffer. The r(2)* relaxivity
      of protons and mass attenuation coefficient of the nanoparticles were determined.
      The particle diameter and surface morphology were studied after neutron
      activation. RESULTS: Spherical particles with a smooth surface and diameter of 78
      +/- 10 nm were obtained, and the particles were stable in buffer. Neutron
      irradiation did not damage the particles, and adequate amounts of activity were
      produced for nuclear imaging and radioablation of malignancies through
      intratumoral injections. CONCLUSIONS: The present study demonstrates that HoAcAc
      nanoparticles were prepared using a solvent evaporation process. The particle
      diameter can easily be adapted and can be optimized for specific therapeutic
      applications and tumor types.

PMID- 20680668
TI  - Mass spectrometric analysis of intact human monoclonal antibody aggregates
      fractionated by size-exclusion chromatography.
AB  - PURPOSE: The aim of this study was to develop a method to characterize intact
      soluble monoclonal IgG1 antibody (IgG) oligomers by mass spectrometry. METHODS:
      IgG aggregates (dimers, trimers, tetramers and high-molecular-weight oligomers)
      were created by subjecting an IgG formulation to several pH jumps. Protein
      oligomer fractions were isolated by high performance size exclusion
      chromatography (HP-SEC), dialyzed against ammonium acetate pH 6.0 (a mass
      spectrometry-compatible volatile buffer), and analyzed by native electrospray
      ionization time-of-flight mass spectrometry (ESI-TOF MS). RESULTS: Monomeric and
      aggregated IgG fractions in the stressed IgG formulation were successfully
      isolated by HP-SEC. ESI-TOF MS analysis enabled us to determine the molecular
      weight of the monomeric IgG as well as the aggregates, including dimers, trimers
      and tetramers. HP-SEC separation and sample preparation proved to be necessary
      for good quality signal in ESI-TOF MS. Both the HP-SEC protocol and the ESI-TOF
      mass spectrometric technique were shown to leave the IgG oligomers largely
      intact. CONCLUSIONS: ESI-TOF MS is a useful tool complementary to HP-SEC to
      identify and characterize small oligomeric protein aggregates.

PMID- 20680669
TI  - The effect of skin incision on the electroencephalogram during general anesthesia
      maintained with propofol or desflurane.
AB  - OBJECTIVE: A variety of effects of surgical incision on the electroencephalogram
      (EEG) during modern general anesthesia have been previously described; including
      both increases and decreases in both high and low frequencies in the EEG. What
      are the patterns commonly seen during routine clinical anesthesia? METHODS: We
      analyzed pre-frontal EEG data from a previously published study (116 adult
      patients having general anesthesia maintained with either desflurane or propofol)
      (Leslie et al. in Anesthesiology 111:547-555, 2009), The EEG was quantified using
      seven estimated parameters: slope and intercept of the underlying non-oscillatory
      (logarithmically transformed) power spectrum, amplitude and frequency of the
      episodic frontal alpha (EFA) oscillation, peak power in the delta waveband, high
      frequency variability index, and bispectral index (BIS). We compared a 30 s EEG
      segment from 2 min before, with that 2 min after the surgical incision. RESULTS:
      The pre-incision EEGs showed a wide spread of different values for the estimated
      EEG parameters, but the propofol group had increased EFA amplitude. Incision was
      associated with decreased EFA activity (p = 0.0004), and high frequency
      variability (p = 0.04, repeated measures ANOVA). The effects of the incision were
      independent of the type of drug used for maintenance of anesthesia, and on the
      pre-incision BIS. The loss of EFA tended to be associated with an increase in
      delta power (r = -0.39, p < 0.0001). CONCLUSIONS: During anesthesia maintained
      with desflurane or propofol, surgical incision has modest effects on the EEG
      patterns. It does not cause an increase in high frequency power; the most
      consistent changes are a loss of EFA amplitude and burst suppression patterns.
      This effect is not strongly modified by the depth of anesthesia--as estimated by
      the BIS.

PMID- 20680670
TI  - Abuse from in-laws during pregnancy and post-partum: qualitative and quantitative
      findings from low-income mothers of infants in Mumbai, India.
AB  - To examine experiences of perinatal (in pregnancy or post-partum) abuse from in
      laws and to assess associations between such experiences and perinatal intimate
      partner violence (IPV) from husbands, as reported by Indian women residing in low
      income communities in Mumbai. The present study includes both qualitative and
      quantitative research conducted across two phases of study. The qualitative phase
      involved face-to-face, semi-structured in-depth interviews (n = 32) with women
      seeking health care for their infants (6 months or younger) and self-reporting
      emotional or physical abuse from their husband. The quantitative arm involved
      survey data collection (n = 1,038) from mothers seeking immunization for their
      infants 6 months or younger at three large Urban Health Centers in Mumbai.
      Results of the qualitative study documented the occurrence of both non-physical
      and physical abuse from in-laws during pregnancy and post-partum. Non-physical
      forms of abuse included forced heavy domestic labor, food denial and efforts
      toward prevention of medical care acquisition. Quantitative results demonstrated
      that 26.3% of the sample reported perinatal abuse (non-physical and physical)
      from in-laws and that women experiencing perinatal sexual or physical IPV from
      husbands were significantly more likely to report perinatal abuse from in-laws
      (AOR = 5.33, 95% CI = 3.93-7.23). Perinatal abuse from in-laws is not uncommon
      among women in India and may be compromising maternal and child health in this
      context; such abuse is also linked to perinatal violence from husbands. Programs
      and interventions that screen and address IPV in pregnant and post-partum
      populations in India should be developed to include consideration of in-laws.

PMID- 20680671
TI  - Antecedents and consequences of caregiving structure on young mothers and their
      infants.
AB  - This study describes the multigenerational caregiving structure of infants born
      to young women, the prenatal predictors of caregiving structure, and the effects
      of caregiving structure on the health of young mothers and their infants 6 months
      postpartum. The sample consisted of 784 young mothers involved in a longitudinal
      study in two U.S. cities. Women were classified into eight caregiving structure
      groups based on the mother's report of herself as a caregiver and her selection
      of the baby's father and/or grandparents as caregivers. ANCOVA analyses
      identified predictors and 6 month postpartum outcomes of caregiving structure.
      Planned comparisons explored the relationships among caregiving structure groups.
      A majority of women reported caregiving structures other than herself and the
      father as caregivers (87.1%). Grandparents were indicated as caregivers by most
      women (62.2%). Postpartum caregiving groups differed on prenatal social support,
      self-esteem, attachment avoidance and anxiety, relationship status, and living
      with the baby's father. While mother's self esteem significantly predicted father
      involvement, there were no differences on predictors between when the mother and
      father were caregivers, versus when the mother and grandparents were caregivers.
      Differences existed between groups on mother and child outcomes, including
      parenting stress, distress, and child dysfunction. Women reported significantly
      less parenting stress, child dysfunction, and negative child emotions when she
      and the father were caregivers, versus when she and grandparents were caregivers.
      The family system and the intergenerational dynamics within a multigenerational
      caregiving structure are critical to the health and well-being of both mothers
      and their children.

PMID- 20680672
TI  - Sports and leisure time physical activity during pregnancy in nulliparous women.
AB  - To describe patterns of leisure time physical activity during pregnancy in
      relation to pre-pregnancy leisure time physical activity, socio-demographic
      characteristics, fertility history, and lifestyle factors. 4,718 nulliparous with
      singleton pregnancy and intended spontaneous vaginal delivery were included in
      the study at gestational week 33 from May 2004 to July 2005. Information was
      provided by self-administered questionnaires. Leisure time physical activity was
      categorised into four categories: competitive sport, moderate-to-heavy, light or
      sedentary. In this population of nulliparous women, 4% participated in
      competitive sport, 25% in moderate-to-heavy activities, 66% in light activities,
      and 5% in sedentary activities in the year prior to pregnancy. Physical activity
      before pregnancy was statistically significantly associated with age, pre
      pregnancy BMI, chronic diseases, number of years at school, and smoking habits.
      The proportion of women who took part in competitive sports, and moderate-to
      heavy activities decreased over the three trimesters of pregnancy. The proportion
      of women with light physical activity was stable during pregnancy while the
      proportion of women with sedentary activity increased from 6% to 29%. During the
      third trimester women performing competitive sports or moderate-to-heavy
      activities before pregnancy continued to have a higher level of physical activity
      than women with light activities or sedentary activities before pregnancy. In
      general the intensity and time spent on exercise decreased during pregnancy.
      Women with the highest level of exercise prior to pregnancy continued to be the
      most active during pregnancy. Among women with sedentary activities before
      pregnancy one-fourth changed to light activity during pregnancy.

PMID- 20680673
TI  - Community norms for HIV risk behaviors among men in a South African township.
AB  - We investigated alcohol-related sexual risk behavior from the perspective of
      social norms theory. Adults (N = 895, 62% men) residing in a South African
      township completed street-intercept surveys that assessed risk and protective
      behaviors (e.g., multiple partners, drinking before sex, meeting sex partners in
      shebeens, condom use) and corresponding norms. Men consistently overestimated the
      actual frequency of risky behaviors, as reported by the sample, and
      underestimated the frequency of condom use. Relative to actual attitudes, men
      believed that other men were more approving of risk behavior and less approving
      of condom use. Both behavioral and attitudinal norms predicted the respondents'
      self-reported risk behavior. These findings indicate that correcting inaccurate
      norms in HIV-risk reduction efforts is worthwhile.

PMID- 20680674
TI  - Behavioral responses to the influenza A(H1N1) outbreak in Malaysia.
AB  - In the setting of the new A(H1N1) outbreak, the study was conducted to assess:
      (1) fear of the A(H1N1) pandemic; (2) risk avoidance behavior; (3) health
      protective behavior; and (4) psychosocial impact in the ethnically diverse
      population of Malaysia. A cross-sectional, computer-assisted telephone interview
      was conducted between July 11 and September 12, 2009. A total of 1,050
      respondents were interviewed. Fear about the pandemic was high, with 73.2% of
      respondents reporting themselves as Slightly fearful/Fearful. High risk avoidance
      and health protective behavior were reported, with 78.0 and 99.0% reporting at
      least one avoidance and protective behavior respectively. Knowledge was a
      significant predictor for practice of healthprotective behavior across the three
      ethnic groups. Level of fear was significantly correlated with number of
      protective and avoidance behaviors. The study highlights the need for provision
      of accurate information that increases risk avoidance and health protective
      behaviors, while at the same time decreases fear or panic in the general public.

PMID- 20680675
TI  - Investigating the relationship between neighborhood experiences and psychiatric
      distress for individuals with serious mental illness.
AB  - The present study examined the relationships between how research participants
      experienced their neighborhood, their neighborhood social climate, and
      psychological well-being. Participants (n = 525) were residents of supported
      housing programs who used mental health services at one of 17 community mental
      health centers in South Carolina. Hierarchical regression and mediation analyses
      were employed to answer research questions. Results suggest that neighbor
      relations, perceptions of neighborhood safety, and neighborhood satisfaction were
      significantly associated with perceptions of neighborhood social climate; and
      neighborhood social climate accounted for a significant amount of the variance in
      psychiatric distress. Of particular interest, perceptions of neighborhood social
      climate fully mediated the relationship between the specific reported
      neighborhood experiences and psychiatric distress. These findings have
      implications for interventions and policy aimed at promoting integration of
      individuals with serious mental illness into community settings.

PMID- 20680676
TI  - Randomized trial of enhanced profiling in substance abuse treatment.
AB  - A randomized trial of substance abuse treatment programs tested whether "enhanced
      profiles," consisting of feedback and coaching about performance indicators,
      improved the performance of residential, methadone, and detoxification programs.
      These enhanced profiles were reviewed during quarterly on-site visits between
      October 2005 and July 2007. The performance indicators were the percentage of
      clients completing referrals to a lower level of care, and the percentage of
      clients admitted to a higher level of care within 30 days of discharge. Control
      programs received only "basic profiles," consisting of emailed quarterly
      printouts of these performance indicators. Effectiveness was evaluated using
      hierarchical linear models with client-level information nested within agencies
      and regions of the state. Treatment programs receiving enhanced profiles (n = 74)
      did not perform significantly differently from those receiving only basic
      profiles (n = 29) on either performance measure. To improve performance,
      interventions with greater scope and incentives may be needed.

PMID- 20680677
TI  - PAC, a novel curcumin analogue, has anti-breast cancer properties with higher
      efficiency on ER-negative cells.
AB  - We have investigated here the anti-breast cancer properties of two novel curcumin
      analogues, EAC and PAC. Apoptosis was assessed by the annexin V/propidium iodide
      (PI) assay on different breast cancer and normal cells. Immunoblotting analysis
      determined the effects of these agents on different apoptotic and oncogenic
      proteins. Furthermore, flow cytometry and Elispot were utilised to investigate
      the effects on the cell cycle and the production of cytokines, respectively.
      Breast cancer tumour xenografts were developed in nude mice. Finally, (18)F
      radiolabeled PAC and curcumin were produced to study their bioavailability and
      tissue biodistribution in mice. PAC is five times more efficient than curcumin
      and EAC in inducing apoptosis, mainly via the internal mitochondrial route. This
      effect was 10-fold higher against ER-negative as compared to ER-positive cells,
      and ectopic expression of ERalpha rendered ER-negative breast cancer cells more
      resistant to PAC. In addition, PAC delayed the cell cycle at G2/M phase with a
      stronger effect on ER-negative cells. Moreover, PAC exhibited strong capacity as
      an immuno-inducer through reducing the secretion of the two major Th2 cytokines
      IL-4 and IL-10. Importantly, PAC significantly reduced tumour size, and triggered
      apoptosis in vivo. Furthermore, PAC inhibited survivin, NF-kB and its downstream
      effectors cyclin D1 and Bcl-2, and strongly up-regulated p21(WAF1) both in vitro
      and in tumours. Besides, PAC exhibited higher stability in blood and greater
      biodistribution and bioavailability than curcumin in mice. These results indicate
      that PAC could constitute a powerful, yet not toxic, new chemotherapeutic agent
      against ER-negative breast tumours.

PMID- 20680678
TI  - No evidence for DNA methylation of von Hippel-Lindau ubiquitin ligase complex
      genes in breast cancer.
AB  - pVHL is the central component of an ubiquitin ligase complex that targets hypoxia
      inducible factor 1alpha (HIF-1alpha) for proteasomal degradation. This complex
      includes four other genes, Cullin 2 (CUL2), elongin C (TCEB1), elongin B (TCEB2)
      and ring-box 1 (RBX1). VHL has previously been reported to be methylated in
      sporadic renal cell carcinoma. Since HIF-1alpha is frequently expressed in breast
      carcinomas, we evaluated DNA methylation as a possible mechanism of silencing one
      or more of the VHL complex genes. Methylation-specific high resolution melting
      (MS-HRM) was used to screen the proximal promoter CpG islands for methylation of
      the VHL ubiquitin ligase complex genes. We were unable to identify methylation of
      any of the five genes in 84 breast carcinoma samples or in a range of cancer cell
      lines including 13 breast cancer cell lines of various subtypes. We were able,
      however, to identify VHL methylation in control renal cell carcinoma samples.
      Epigenetic silencing by promoter DNA methylation for VHL and the complex genes,
      CUL2, elongin C (TCEB1), elongin B (TCEB2) and RBX1, is unlikely to play a role
      in HIF-1alpha upregulation in breast carcinomas.

PMID- 20680679
TI  - Sentinel node micrometastases in breast cancer do not affect prognosis: a
      population-based study.
AB  - Sentinel node biopsy (SNB) for axillary staging in breast cancer allows the
      application of more extensive pathologic examination techniques. Micrometastases
      are being detected more often, however, coinciding with stage migration. Besides
      assessing the prognostic relevance of micrometastases and the need for
      administering adjuvant systemic and regional therapies, there still seems to be
      room for improvement. In a population-based analysis, we compared survival of
      patients with sentinel node micrometastases with those with node-negative and
      node-positive disease in the era after introduction of SNB. Data from the
      population-based Eindhoven Cancer Registry were used on all (n = 6803) women who
      underwent SNB for invasive breast cancer in the Southeast Region of The
      Netherlands in the period 1996-2006. In 451 patients (6.6%) a sentinel node
      micrometastasis (pN1mi) was detected and in 126 patients (1.9%) isolated tumor
      cells (pN0(i+)). Micrometastases or isolated tumor cells in the SNB did not
      convey any significant survival difference compared with node-negative disease.
      After adjustment for age, pT, and grade, still no survival difference emerged
      pN1mi: [HR 0.9 (95% CI, 0.6-1.3)] and pN0(i+): [HR 0.4 (95% CI, 0.14-1.3)] and
      neither was the case after additional adjustment for adjuvant systemic therapy.
      Our practice-based study showed that the presence of sentinel node
      micrometastases in breast cancer patients has hardly any impact on breast cancer
      overall survival during the first years after diagnosis.

PMID- 20680680
TI  - Quality of life in women with metastatic breast cancer during 9 months after
      randomization in the TEX trial (epirubicin and paclitaxel w/o capecitabine).
AB  - The aim of this study was to compare the effects on health-related quality of
      life (HRQOL) of two treatment regimens in the TEX trial during 9 month from
      random assignment, with emphasis on the 2- and 9-months assessments. A total of
      287 patients were randomized to treatment in 3-week cycles with either epirubicin
      plus paclitaxel (ET, 143 patients), or epirubicin, paclitaxel and capecitabine
      (TEX, 144 patients). HRQOL was assessed by the EORTC-QLQ C30 and EORTC QLQ-BR23
      questionnaires at five points during 9 months. A total of 252 (88%) completed
      questionnaires before randomization. Response rate for the following assessments
      was >75%. There were no statistically significant differences between the TEX
      group and the ET group on any of the subscales 2 months after randomization.
      Small clinical differences (5-10 points) in favor of the ET group were found for
      global quality of life, role functioning, social functioning, and insomnia. At
      the 9-months assessment, the TEX group scored statistically significantly higher
      on global quality of life and physical functioning. Small clinically significant
      differences were found for global quality of life, physical functioning, role
      functioning, emotional functioning, dyspnoea, and insomnia, all in favour of the
      TEX group. At the 2-months assessment, when side-effects of chemotherapy were
      present, patients in the TEX group appeared to fare a bit worse than those
      receiving ET. However, after 9 months, when the patients had adapted to
      treatment, the TEX group seemed to have a slightly better quality of life.

PMID- 20680681
TI  - Anti-angiogenic effect of tamoxifen combined with epirubicin in breast cancer
      patients.
AB  - Vascular endothelial growth factor A (VEGF-A) and vascular endothelial growth
      factor receptor 2 (VEGFR2) are the key factors mediating neo-vascularization.
      They are often coexpressed in breast cancer. Sex steroids may stimulate
      angiogenesis via the estrogen receptor (ER) pathway. We investigated to compare
      the effects of the addition of tamoxifen to epirubicin versus epirubicin alone on
      VEGF and VEGFR2 expression in breast cancer patients. The expression of VEGF and
      VEGFR2 was assessed on tissue microarray by immunohistochemistry at baseline
      conditions and after treatments in the case of 191 patients with T2-4 N0-1 breast
      cancer enrolled in a randomized trial comparing four cycles of single agent
      epirubicin versus epirubicin plus tamoxifen as primary systemic treatment.
      Epirubicin alone failed to induce changes in VEGF expression (P = 0.54), while
      the addition of tamoxifen to epirubicin resulted in a significant reduction in
      VEGF expression (P < 0.001). As a consequence, baseline VEGF had a negative
      prognostic role in patients who received epirubicin alone but not in patients
      receiving epirubicin plus tamoxifen (interaction test P < 0.05). VEGFR2
      expression increased at residual tumor histology in both treatment arms, with a
      lesser extent in patients receiving tamoxifen plus epirubicin. Decrease in VEGFR2
      expression was significantly associated with response rate (P = 0.02). The
      addition of tamoxifen to epirubicin resulted in a suppression of a key angiogenic
      pathway. These data suggest a potential synergism of these two drugs.

PMID- 20680682
TI  - Investigating the establishment of primary cell culture from different abalone
      (Haliotis midae) tissues.
AB  - The abalone, Haliotis midae, is the most valuable commodity in South African
      aquaculture. The increasing demand for marine shellfish has stimulated research
      on the biology and physiology of target species in order to improve knowledge on
      growth, nutritional requirements and pathogen identification. The slow growth
      rate and long generation time of abalone restrict efficient design of in vivo
      experiments. Therefore, in vitro systems present an attractive alternative for
      short term experimentation. The use of marine invertebrate cell cultures as a
      standardised and controlled system to study growth, endocrinology and disease
      contributes to the understanding of the biology of economically important
      molluscs. This paper investigates the suitability of two different H. midae
      tissues, larval and haemocyte, for establishing primary cell cultures. Cell
      cultures are assessed in terms of culture initiation, cell yield, longevity and
      susceptibility to contamination. Haliotis midae haemocytes are shown to be a more
      feasible tissue for primary cell culture as it could be maintained without
      contamination more readily than larval cell cultures. The usefulness of short
      term primary haemocyte cultures is demonstrated here with a growth factor trial.
      Haemocyte cultures can furthermore be used to relate phenotypic changes at the
      cellular level to changes in gene expression at the molecular level.

PMID- 20680683
TI  - Rhodotorula taiwanensis sp. nov., a novel yeast species from a plant in Taiwan.
AB  - A novel anamorphic yeast strain, A1-01(T), belonging to the genus Rhodotorula was
      isolated from a plant in Taiwan and analysed morphologically, physiologically and
      phylogenetically. Neither ballistoconidia nor sexual reproduction was observed.
      Sequence analysis of the 26S rRNA gene and the ITS region indicate that
      Rhodosporidium sphaerocarpum is the most closely related species, with 14 and 24
      nucleotide substitutions, respectively. The novel species differed
      physiologically from R. sphaerocarpum in its ability to assimilate ethylamine and
      cadaverine, its inability to assimilate ethanol and nitrite. From these
      comparative analyses, the following novel yeast species is proposed: Rhodotorula
      taiwanensis sp. nov. with the type strain of A1-01(T) (BCRC 23118(T) = CBS
      11729(T)).

PMID- 20680684
TI  - Spiritual well-being among older african americans in a midwestern city.
AB  - More than many other cities in America, older African Americans in Milwaukee, WI
      contend with negative environmental, socio-economic and health challenges in one
      of the most hyper-segregated cities in America. This research examines the role
      of spirituality and religion in their lives and the ways that spirituality and
      religious affiliation contribute to their quality of life. Over 500 elderly
      respondents aged 55-105 completed a questionnaire. The analysis found: (a) strong
      identification with religious institutions and high levels of attendance and
      participation in religious activities, (b) a substantial number felt support from
      fellow church members, and (c) strong reliance on spirituality and their sense of
      connection to God as sources of strength in coping with personal challenges. This
      study adds to the findings of other research done which stressed the importance
      of spirituality, religious practice and congregational assistance in serving
      critical survival functions for older African Americans. This is the first such
      research done, however, reporting on Milwaukee's African American older adults.
      This study used mixed methods of research, conducting both a descriptive
      statistical analysis of African American elderly in Milwaukee County to develop a
      profile while simultaneously gathering, where possible, qualitative data as well,
      in the form of narratives, written comments and field notes of first hand
      observations on this growing population.

PMID- 20680685
TI  - Fluorescent viability stains to probe the metabolic status of aflatoxigenic
      fungus in dual culture of Aspergillus flavus and Pichia anomala.
AB  - The metabolic activity of the aflatoxigenic fungus, Aspergillus flavus co
      cultured with the biocontrol yeast, Pichia anomala was examined using several
      viability stains. Both the FUN-1 stain and the combined use of DiBAC(4)(5) with
      CDFA-AM stains were applied in this study. The results suggest that the ATP
      generating system in A. flavus was inactivated as the ratio of yeasts to fungi
      increased in the dual culture. A decrease in hyphal membrane potential and
      esterase activity was substantiated by the combined stains of DiBAC(4)(5) and
      CDFA-AM. Reduced metabolic function in conjunction with cell wall damage of A.
      flavus hindered the growth and biomass production of this fungus. Viability
      stains such as FUN-1 and DiBAC(4)(5) with CDFA-AM may assist in elucidating the
      biocontrol mechanism by allowing for the visualization of the antagonistic effect
      of yeast species on target fungi in situ, as well as for screening potent
      biocontrol yeast agents against fungal pathogens.

PMID- 20680686
TI  - Inhibition of virulence factors of Candida spp. by different surfactants.
AB  - Candida yeasts are opportunistic pathogens responsible for infections in
      immunocompromised individuals. Among the virulence factors present in these
      yeasts we can mention the ability to adhere to host cells, exoenzyme production
      and germ tube formation. Several compounds, such as antifungal agents, plants
      extracts, protein inhibitors and surfactants, have been tested regarding their
      capacity in inhibit Candida spp. virulence factors. Among these compounds, a
      significant lower number of works are focused on the inhibition action caused by
      different types of surfactant. The present work aimed to evaluate the effect
      generated by the surfactants cetyltrimethylammonium chloride (CTAC), sodium
      dodecyl sulfate (SDS), N-hexadecyl-N-N'-dimethyl-3-ammonio-1-propane-sulfonate
      (HPS) and octylphenoxypolyethoxyethanol (Triton X-100) on the viability, adhesion
      ability and exoenzyme production by Candida species. CTAC and HPS were capable to
      inhibit Candida spp. growth at very low concentrations. All surfactants
      demonstrated to be capable to inhibit the adhesion of Candida species to buccal
      epithelial cells (BEC) and the proteinase production. On the other hand, the
      phospholipase production remained unaltered after the treatment with these
      compounds. The present data denote that cationic and zwitterionic surfactants are
      interesting prototypes of inhibitory agents against Candida spp., which is
      probably associated with the cationic punctual charge of both surfactants. The
      results are discussed in details in agreement with recent reports from
      literature.

PMID- 20680687
TI  - Long-term quality of life following primary treatment in men with clinical stage
      T3 prostate cancer.
AB  - OBJECTIVES: We evaluated the changes of health-related quality of life (HRQOL)
      during the 5 years after radical prostatectomy (RP) or external beam radiation
      therapy (EBRT) for clinical stage T3 prostate cancer (cT3PC). PATIENTS AND
      METHODS: A total of 750 patients who underwent RP (n = 575) or EBRT (n = 175)
      participated in our longitudinal outcomes study. Of these patients, 48 RP
      patients (8%) and 63 EBRT patients (36%) presented with cT3PC and were included
      in this analysis. Patients completed the general and disease-specific HRQOL with
      the Short Form 36 (SF-36) and University of California, Los Angeles Prostate
      Cancer Index, respectively. RESULTS: When examining the mean SF-36 values by
      time, there was significant impact on treatment outcomes for several items of the
      general HRQOL in the RP subjects. Those who underwent EBRT reported no
      significant changes in the general HRQOL throughout the follow-up period. With
      regard to disease-specific HRQOL, the RP subjects had significantly worse urinary
      HRQOL post-operatively than the EBRT subjects (P < 0.001). The scores for sexual
      function declined over the 60 months, but more so in the RP group. The two groups
      showed similar bowel HRQOL scores throughout the follow-up periods. CONCLUSIONS:
      Both primary treatments for cT3PC can offer satisfactory functional outcomes from
      the HRQOL perspective, except for a persistent decrease in the sexual activity
      score. These results may guide the treatment selection and clinical management of
      patients with HRQOL impairments after treatment for cT3PC.

PMID- 20680688
TI  - The Persian version of locomotor capabilities index: translation, reliability and
      validity in individuals with lower limb amputation.
AB  - PURPOSE: To translate the Locomotor Capabilities Index (LCI-5) to Persian and to
      assess its psychometric properties when applied to a sample of people with lower
      limb amputation (LLA). METHODS: The LCI-5 was administered to 106 Persian
      speaking people with LLA to determine its internal consistency, item-subscale
      correlation, test-retest reliability and floor and ceiling effects. To assess the
      construct validity, each participant's performance was measured using the Timed
      Up and Go (TUG) and 2-Minute Walk Test. RESULTS: Minimum Cronbach's alpha of 0.70
      was exceeded by LCI-5 subscales. Item-subscale correlations after correction for
      overlap were higher than the cuff-off point of 0.40. The intraclass correlation
      coefficient was 0.96 for LCI-5 total index in test-retest reliability. LCI-5
      showed significant correlation with TUG (r = -0.65, P < 0.01) and 2-Minute Walk
      Test (r = 0.71, P < 0.01). The LCI-5 mean scores were higher for individuals with
      unilateral below-knee amputation than participants with above-knee amputation (t
      = 2.71, P = 0.008) and for individuals with unilateral amputation who do not use
      walking aids than those who use (t = -4.27, P < 0.01). Floor effect was found for
      none of the patients with LLA while ceiling effect was reported for 23.6% of
      patients. CONCLUSIONS: The Persian version of LCI-5 has acceptable levels of
      internal consistency, item-subscale correlation, test-retest reliability and
      construct validity. To detect intervention effects, the LCI-5 should be used
      cautiously in population of physically active and young patients with LLA due to
      its high ceiling effects.

PMID- 20680689
TI  - Predicting moderate improvement and decline in pediatric asthma quality of life
      over 24 months.
AB  - OBJECTIVE: To determine factors associated with 24-month change in quality of
      life in children with asthma and their parents during the Childhood Asthma
      Management Program (CAMP). METHODS: Participants from 4 CAMP clinical centers
      were administered the Pediatric Asthma Quality of Life questionnaire and protocol
      measures of asthma symptoms, lung function, and psychological measures. RESULTS:
      Multivariate logistic regression analyses determined predictors of moderate
      change in quality of life. Subclinical levels of depression predicted moderate
      improvement in child-reported quality of life. Level of depressed affect together
      with clinical asthma features predicted moderate decline. Improvement in parent
      quality of life was predicted by perception of illness burden, whereas family
      features and a child missing school predicted moderate decline. CONCLUSIONS: This
      ancillary study provided an opportunity to examine the determinants of 24-month
      change in parent and child of quality of life within a subset of the CAMP
      participants. Moderate changes in quality of life occur in clinical studies and
      have both psychosocial correlates and illness characteristics.

PMID- 20680690
TI  - Valuing health in a racially and ethnically diverse community sample: an analysis
      using the valuation metrics of money and time.
AB  - PURPOSE: Limited research in health valuation analyzes samples with high
      proportions of racial/ethnic minorities within the United States. The primary
      objective was to explore patterns of health valuation across race/ethnicity using
      the Collaborative Psychiatric Epidemiology Surveys. A secondary objective was to
      analyze whether mental health disorder and immigrant status were associated with
      these estimates. METHODS: Health valuation questions using different metrics
      (time and money) were analyzed. Ordered logit models stratified across poor and
      moderate health tested differences by race/ethnicity, with mental health disorder
      and immigrant status as covariates. RESULTS: Asians in moderate health and
      Latinos were willing to pay more for health than non-Latino whites. Asians in
      moderate health were willing to trade more time for health. Latinos in poor
      health were less willing to trade time and gave disproportionate zero-trade
      responses. Lifetime history of anxiety disorder was positively associated with
      both metrics. Immigrant status confounded money valuation for Asians in moderate
      health, and time valuation for Latinos in poor health. CONCLUSIONS: Health
      valuation estimates vary across race/ethnicity depending upon the metric. Time
      valuation scenarios appear less feasible for Latinos in poor health. More
      research is necessary to understand these differences and the role of immigrant
      status in health valuation.

PMID- 20680691
TI  - Quality of life in relation to upper and lower respiratory conditions among
      retired 9/11-exposed firefighters with pulmonary disability.
AB  - PURPOSE: To examine health-related quality of life (HRQoL) and World Trade Center
      (WTC) cough syndrome conditions in male firefighters who retired due to a 9/11
      related pulmonary disability. METHODS: From 3/1/2008 to 1/31/2009, we contacted
      275 disability-retired firefighters and compared their HRQoL and current
      aerodigestive conditions to those from WTC-exposed non-disabled retired and
      active firefighters. Relationships between HRQoL and explanatory variable(s) were
      examined using multivariable linear regression models. RESULTS: Mean physical
      component summary (PCS) scores were lowest in disabled retirees compared with non
      disabled retirees and actives: 36.4 (9.6), 49.4 (8.7), and 53.1 (5.1),
      respectively (P < 0.0001). Mean mental component summary (MCS) scores were
      closer: 44.5 (11.9), 48.1 (8.5), and 48.7 (7.4), respectively (P < 0.0001). In
      multivariable models, after adjustment for many factors, PCS scores were not
      associated with early WTC arrival, but were inversely associated with disability
      retirement and all WTC cough syndrome conditions. MCS scores were inversely
      associated with early WTC arrival and most WTC cough syndrome conditions, but
      were not associated with disability retirement. CONCLUSION: WTC cough syndrome
      conditions predict lower HRQoL scores even 8 years after exposure, independent of
      retirement status. These data suggest that monitoring physical conditions of
      individuals with occupational exposures might help identify those at risk for
      impaired HRQoL.

PMID- 20680692
TI  - Epitrochlear lymph node dissection.
AB  - Epitrochlear node involvement occurs in a small minority of patients with forearm
      or hand melanoma. Although in-transit sentinel lymph nodes are identified
      infrequently, they contain metastatic disease at nearly the same frequency as
      sentinel lymph nodes in cervical, axillary, and inguinal nodal basins. Positive
      in-transit sentinel lymph nodes are likely to be the only site of nodal
      metastasis. Therefore, detailed preoperative lymphoscintigraphy and meticulous
      intraoperative search for in-transit nodes should be performed. The recovery of
      nodes from in-transit nodal areas is low; however, there appears to be an
      increase in the performance of these dissections since the advent of lymphatic
      mapping and sentinel lymph node biopsy. This streaming video demonstrates the
      incidence of epitrochlear lymph node involvement and technical considerations
      associated with epitrochlear lymph node dissection.

PMID- 20680693
TI  - Prognostic significance of the alterations of the G1-S checkpoint in localized
      leiomyosarcoma of the peripheral soft tissue.
AB  - BACKGROUND: The aim of this study was to investigate the expression of cell cycle
      regulators p53, p16, cyclin-D1, and retinoblastoma (Rb) gene protein in
      leiomyosarcoma of the peripheral soft in order to identify expression profiles
      potentially useful for clinical prognostic purposes. MATERIALS AND METHODS: A
      tissue microarray representing 70 localized leiomyosarcomas of the limbs and limb
      girdles was created with 3 representative cores from each tumor.
      Immunohistochemical staining was performed for p53, p16, cyclin-D1, and Rb using
      standard techniques. Staining was scored as either absent-low (<20% of neoplastic
      cells) or moderate-diffuse (>=20%). Outcome analysis was performed for local
      recurrence-free survival (LFS), metastatic disease-free survival (MDFS), and
      disease-specific survival (DSS). RESULTS: Kaplan-Meier analysis of survival
      revealed that no single alteration of the factors examined was associated with
      outcome, but tumors showing concomitant alteration of p16 and p53 were
      characterized by reduced MDFS and DSS (P = 0.01 and P < 0.001, respectively). In
      addition, patients who received adjuvant therapy consisting of radiotherapy alone
      or radiotherapy and chemotherapy had a better DSS than those receiving surgery
      alone or surgery and chemotherapy (P = 0.05). In multivariate analysis, altered
      p16/p53 remained the only parameter predictive of MDFS and DSS (P = 0.048, hazard
      ratio [HR] = 2.488, 95% confidence interval [95% CI] 1.006-5.116; P = 0.043, HR =
      2.498, 95% CI 1.029-5.909, respectively). CONCLUSIONS: Accumulation of cell cycle
      alterations represents a prognostic indicator in localized soft tissue
      leiomyosarcoma, and in particular altered p16/p53 expression is associated with
      an unfavorable prognosis. This may help the clinical management of patients with
      leiomyosarcomas.

PMID- 20680694
TI  - Lymphadenectomy for melanoma: toward a videoscopic approach.

PMID- 20680695
TI  - The learning curve for robotic thyroidectomy: a multicenter study.
AB  - PURPOSE: The learning curve for robotic thyroidectomy with central compartment
      node dissection (CCND) has not been established. We examined the effect of
      experience of robotic thyroidectomy on a range of perioperative parameters in
      order to determine the learning curve. The learner surgeon outcomes were compared
      with those of an experienced surgeon. METHODS: We conducted a prospective,
      controlled, multicenter study involving four endocrine surgeons at three academic
      centers. Patients underwent robotic total or subtotal thyroidectomy with CCND
      between September 2008 and October 2009. One surgeon was experienced in the
      technique (experienced surgeon, ES), while the other three surgeons had
      endoscopic thyroid surgery experience but no experience performing the robotic
      procedure (nonrobotic thyroid surgery experienced surgeon, NS). Outcome measures
      were demographic data, operative time, blood loss, hospital stay, pathologic
      results, and postoperative complications. RESULTS: A total of 644 total or
      subtotal robotic thyroidectomies with CCND were performed: 377 (58.7%) by NSs and
      267 (41.5%) by the ES. Mean operative time was longer and the complication rate
      was higher for the NS patient group compared with the ES patient group (P < 0.001
      for each). The operative times and complications rates for the NS group were
      similar to those of the ES group once the NSs had performed 50 cases for total
      thyroidectomies or 40 cases for subtotal thyroidectomies. CONCLUSION: The
      learning curve duration for robotic thyroidectomy with CCND using gasless
      transaxillary approach for experienced endoscopic thyroidectomy surgeons was 50
      cases for total thyroidectomy and 40 cases for subtotal thyroidectomy.

PMID- 20680696
TI  - Radiocolloid in combination with methylene dye localization, rather than wire
      localization, is a preferred procedure for excisional biopsy of nonpalpable
      breast lesions.
AB  - BACKGROUND: Wire localization (WL) is traditionally performed before excisional
      biopsy for patients with nonpalpable breast lesions, but it has several
      disadvantages. Our current study examines whether the method of radiocolloid
      combined with methylene dye localization (RCML) has an advantage over WL.
      MATERIALS AND METHODS: From August 2006 to May 2009, 157 patients with
      nonpalpable breast lesions classified as BI-RADS category 5 were enrolled in our
      study. Of the 157 patients, 78 were assigned to WL and 79 to RCML. The status of
      surgical margins, weight of specimens, length of incisions, and duration of
      operation were compared between these two groups. RESULTS: All patients were
      diagnosed after first excisional biopsy. The patients with malignancy accounted
      for 55.1% in WL group, and 53.2% in RCML group. For malignant lesions, fewer
      patients undergoing RCML had close or involved surgical margins than did those
      who had WL (19.0% vs. 39.5%, P = .038). The mean weight of specimen was 45.2 g in
      WL group and 39.0 g in RCML group (P < .001). The mean length of incision was
      44.8 mm in WL group and 36.3 mm in RCML group (P < .001). The mean time of
      operation was 16.3 min for WL and 14.7 min for RCML (P = .001). CONCLUSIONS: RCML
      provides precise identification of the site of the nonpalpable lesion and a
      visible marker to the lesion for surgeons and allows rapid, easy, and accurate
      excision of nonpalpable breast lesions. Therefore, RCML is a promising
      alternative to WL.

PMID- 20680697
TI  - Adjuvant chemoradiation therapy for adenocarcinoma of the distal pancreas.
AB  - BACKGROUND: This study was designed to examine the effect of adjuvant 5-FU-based
      chemoradiation therapy (CRT) after distal pancreatectomy for adenocarcinoma of
      the distal pancreas. METHODS: All patients underwent curative resection for
      adenocarcinoma of the distal pancreas between December 1985 and June 2006.
      Patients who received adjuvant CRT were compared with those who underwent surgery
      alone. A Kaplan-Meier estimate of the survival curve was used to determine
      estimates of the median survival and proportion alive at 1 and 2 years; log-rank
      tests were used to make comparisons between groups. RESULTS: A total of 123
      patients underwent distal pancreatectomy; 29 patients were excluded for distant
      metastases at the time of surgery (n = 12, 10%) or before adjuvant therapy (n =
      11, 9%), death within 2 months of surgery (n = 2, 2%), or if CRT treatment status
      was unknown (n = 4, 3%). Of the remaining 94 patients, 72% received adjuvant 5-FU
      based CRT and 28% underwent surgery alone. Overall median survival was 16.2 (95%
      confidence interval (CI), 13.1-18.9) months. The groups were similar with respect
      to tumor size, nodal status, and margin status. There was no significant
      difference in overall survival between patients treated with adjuvant CRT versus
      surgery alone (p = 0.23). An exploratory subgroup analysis suggested a potential
      survival benefit of adjuvant CRT in patients with lymph node metastases (16.7 vs.
      12.1 months, p < 0.01). CONCLUSIONS: Adjuvant CRT did not increase survival
      compared with surgery alone; however, patients with node-positive disease appear
      to benefit from adjuvant CRT.

PMID- 20680698
TI  - PAH desorption from sediments with different contents of organic carbon from
      wastewater receiving rivers.
AB  - BACKGROUND AND AIM: Many rivers have to receive treated or untreated wastewater
      as the main water sources in the world, especially in the countries facing with
      water shortage. For instance, the Haihe and Huaihe River Basin, which are among
      areas facing crises for water resources in China, receive 33,400 million tons of
      wastewater per year. As the sediment has large capacity for sorbing hydrophobic
      organic pollutants such as polycyclic aromatic hydrocarbons (PAHs), it can act as
      a natural repository for the contaminants. This means pollutants can release into
      water phase again under some conditions, such as resuspension, sediment dredging,
      etc. The objective of this research was to study the trends of PAH release from
      sediments in rivers receiving much wastewater, such as Yongding New River (YD),
      Northsewer (NS), and Southsewer (SS) from Haihe River Basin. These rivers
      received most of the wastewater from Tianjin, China and merge into Bohai Bay
      finally. METHODS: Sediments (namely YD, NS, and SS) were collected from Yongding
      New River, Northsewer, and Southsewer, respectively. The physical and chemical
      properties of the sediments, including particle size distribution, total organic
      carbon (TOC) and black carbon (BC) contents, elemental compositions, organic
      functional groups analyzed from Fourier transformed infrared (FTIR), and nuclear
      magnetic resonance (NMR) spectra, were characterized. PAH desorption from the
      sediments was measured with the Tenax shaken slurry desorption method. RESULTS:
      The NS sediment had a greatly higher TOC and BC contents, while lower BC-to-TOC
      ratio than YD and SS sediments. NMR and FTIR analysis showed that aliphatic
      carbons were more abundant in NS sediment than SS sediment. The desorption
      experiments showed that PAHs desorbed more rapidly from YD and NS sediments than
      from SS sediment. PAH fraction desorbed after each interval during the experiment
      except 0.8 day was significantly correlated with PAH properties among all the
      three sediments. DISCUSSION: The higher BC-to-TOC ratio in SS sediment
      corresponded to slower desorption rate and less desorption extent of PAHs from SS
      sediment among the three sediments. This probably could be explained by the
      extremely strong sorption ability of BC. It also proved that the sequestration of
      PAHs in sediment was not simply the result of higher organic carbon content.
      CONCLUSIONS: Considering the physical and chemical characterization of the
      sediments and PAH desorption properties comprehensively, BC-to-TOC ratio was a
      more important factor controlling the behavior of PAHs in sediments than absolute
      TOC or BC content.

PMID- 20680699
TI  - Status of feral oilseed rape in Europe: its minor role as a GM impurity and its
      potential as a reservoir of transgene persistence.
AB  - PURPOSE: Feral oilseed rape has become widespread in Europe on waysides and waste
      ground. Its potential as a source of GM impurity in oilseed rape harvests is
      quantified, for the first time, by a consistent analysis applied over a wide
      range of study areas in Europe. METHODS: The maximum contribution of feral
      oilseed rape to impurities in harvested crops was estimated by combining data on
      feral abundance and crop yield from five established, demographic studies in
      agricultural habitats in Denmark, Germany (2), France and the UK, constituting
      over 1,500 ha of land and 16 site-years of observations. Persistence of feral
      populations over time was compared by visual and molecular methods. RESULTS:
      Ferals had become established in all regions, forming populations 0.2 to 15 km-2.
      The seed they produced was always <0.0001% of the seed on crops of oilseed rape
      in each region. The contribution of ferals to impurity in crops through
      accidental harvest of seed and through cross-pollination would be an even smaller
      percentage. Feral oilseed rape nevertheless showed a widespread capacity to
      persist in all regions and retain traits from varieties no longer grown.
      CONCLUSIONS: Feral oilseed rape is not a relevant source of macroscopic impurity
      at its present density in the landscape but provides opportunity for genetic
      recombination, stacking of transgenes and the evolution of genotypes that under
      strong selection pressure could increase and re-occupy fields to constitute an
      economic weed burden and impurity in future crops.

PMID- 20680700
TI  - Time to take a breath.
AB  - With health care reform the law of the land, we must be ready to compete on a new
      playing field where increasing numbers of individuals will have healthcare
      insurance benefits. Our job is to ensure that their new benefits result in access
      to effective behavioral health services. The National Council for Community
      Behavioral Healthcare has led breathtaking initiatives to make access to care
      more timely, to create structures for collaborative care for shared patients, to
      enhance the knowledge, skills, and abilities of psychiatrists who are medical
      directors in community behavioral health centers, and to combat stigma, educate
      key audiences, and improve awareness of treatment options for individuals with
      mental illnesses.

PMID- 20680701
TI  - Epilepsy audit: do we document everything?
AB  - BACKGROUND: An audit of the hospital notes and letters of patients with epilepsy
      sent to general practitioners was undertaken. AIMS: (a) To examine the frequency
      of important omissions in history taking and role of precipitants in seizure
      control, (b) to determine whether appropriate investigations had been performed
      and their results, (c) to assess whether letters sent to GPs contain all the
      appropriate information and advice, and to evaluate the waiting time for out
      patient clinics and investigations. METHODS: This retrospective study was
      conducted in a teaching hospital setting. A computerised search of the clinical
      database of a consultant neurologist was performed on patients with epilepsy. The
      notes of the first 100 names selected randomly by the computer were analysed. The
      study period was during the years 1998-2005. Age range was from 17-72 years. The
      male:female ratio was 1:1. CONCLUSION: Major deficiencies in documentation were
      identified in this study.

PMID- 20680702
TI  - Diagnosis and microsurgery of symptomatic spontaneous spinal epidural hematoma.
AB  - BACKGROUND: Symptomatic spontaneous spinal epidural hematoma (SSEH) is an
      uncommon cause of cord compression that needs emergent treatment. Without
      effective management of the symptomatic SSEH, irreversible severe spinal injury
      would be possible. OBJECTIVES: We aimed to investigate the diagnosis and surgical
      management of symptomatic SSEH. METHODS: Five cases of symptomatic SSEH with
      favorable neurological recovery after emergent microsurgery were prospectively
      analysed. RESULTS: The main clinical presentations were root pain and palsy. The
      main manifestations of MRI were long-segment epidural lesions of high intensity
      on T1- and T2-weighted images without enhancement. Laminectomy via posterior
      approach and hematoma removal were undergone for all patients. All patients
      achieved full neurological recovery without complications. CONCLUSIONS: MRI
      manifestation assisted with the main clinical symptoms may aid the preoperative
      diagnosis of SSEH, and the delay in obtaining preoperative Digital subtraction
      angiography is worthwhile, especially for those with progressive neurological
      deterioration.

PMID- 20680703
TI  - In vivo canine model comparison of cardiovascular effects of antidepressants
      milnacipran and imipramine.
AB  - Milnacipran is a specific serotonin and norepinephrine reuptake inhibitor, which
      has been widely used against major depressive episodes. In this study,
      cardiovascular effects of milnacipran were assessed in comparison with those of a
      typical tricyclic antidepressant imipramine using the halothane-anesthetized
      dogs. Milnacipran (n = 6) or imipramine (n = 6) was intravenously administrated
      in three escalating doses of 0.1, 1 and 10 mg/kg over 10 min with a pause of 20
      min between the doses. Clinically relevant plasma concentrations were obtained
      after 0.1-1 mg/kg of milnacipran in this study, whereas therapeutic dose and
      plasma concentration of imipramine were reported to be similar to those of
      milnacipran. The low and middle doses of milnacipran hardly affected
      cardiohemodynamic or electrophysiological variables except that they slightly
      increased vascular tone and ventricular contraction, whereas same doses of
      imipramine delayed repolarization process without affecting the other variables.
      The high dose of both milnacipran and imipramine induced similar extent of
      negative chronotropic, inotropic and dromotropic effects together with
      vasoconstriction and repolarization delay. Thus, the effects of milnacipran may
      be more selective for cardiohemodynamics than for repolarization delay, whereas
      reverse will be true for imipramine, supporting lack of clinical report of
      patients with milnacipran-induced long QT syndrome unlike imipramine.

PMID- 20680705
TI  - Coping strategies in chronic pain.
AB  - Patients with chronic pain need strategies to manage their pain and its impact,
      also known as coping. Coping is not restricted to one dimension of functioning;
      it involves virtually every dimension of human functioning: cognitive, affective,
      behavioral, and physiological. We review the literature on coping strategies for
      chronic pain, including concept and types of coping (eg, religious, social,
      psychological), as well as coping-with-pain questionnaires, studies available,
      other topics of interest, interventions to enhance coping with pain, and future
      directions in this field.

PMID- 20680706
TI  - Acute brain metabolic effects of cocaine in rhesus monkeys with a history of
      cocaine use.
AB  - Cocaine addiction involves an escalation in drug intake which alters many brain
      functions. The present study documented cocaine-induced changes in brain
      metabolic activity as a function of cocaine self-administration history.
      Experimentally naive rhesus monkeys (N = 6) were given increasing access to
      cocaine under a fixed-ratio schedule of intravenous (i.v.) drug self
      administration. PET imaging with F-18 labeled fluorodeoxyglucose (FDG) was used
      to measure acute intramuscular (i.m.) cocaine-induced changes in brain metabolism
      in the cocaine-naive state, following 60 sessions under limited-access conditions
      (1 h/day), following 60 sessions under extended-access conditions (4 h/day), and
      following 4 weeks of drug withdrawal. In the cocaine-naive state, cocaine-induced
      increases in brain metabolism were restricted to the prefrontal cortex. As
      cocaine exposure increased from limited to extended access, metabolic effects
      expanded throughout the frontal cortex and were induced within the striatum.
      Conversely, cocaine-induced activation was far less robust following withdrawal.
      The results highlight a progressive expansion of the metabolic effects of cocaine
      to include previously unaffected dopamine innervated brain regions as a
      consequence of cocaine self-administration history. The identification of brain
      regions progressively influenced by drug exposure may be highly relevant toward
      efforts to develop treatments for cocaine addiction.

PMID- 20680704
TI  - An introduction to sphingolipid metabolism and analysis by new technologies.
AB  - Sphingolipids (SP) are a complex class of molecules found in essentially all
      eukaryotes and some prokaryotes and viruses where they influence membrane
      structure, intracellular signaling, and interactions with the extracellular
      environment. Because of the combinatorial nature of their biosynthesis, there are
      thousands of SP subspecies varying in the lipid backbones and complex phospho-
      and glycoheadgroups. Therefore, comprehensive or "sphingolipidomic" analyses
      (structure-specific, quantitative analyses of all SP, or at least all members of
      a critical subset) are needed to know which and how much of these subspecies are
      present in a system as a step toward understanding their functions. Mass
      spectrometry and related novel techniques are able to quantify a small fraction,
      but nonetheless a substantial number, of SP and are beginning to provide
      information about their localization. This review summarizes the basic metabolism
      of SP and state-of-art mass spectrometric techniques that are producing insights
      into SP structure, metabolism, functions, and some of the dysfunctions of
      relevance to neuromedicine.

PMID- 20680707
TI  - Analysis of relationships between solid-state properties, counterion, and
      developability of pharmaceutical salts.
AB  - The solid-state properties of pharmaceutical salts, which are dependent on the
      counterion used to form the salt, are critical for successful development of a
      stable dosage form. In order to better understand the relationship between
      counterion and salt properties, 11 salts of procaine, which is a base, were
      synthesized and characterized using a variety of experimental and computational
      methods. Correlations between the various experimental and calculated
      physicochemical properties of the salts and counterions were probed. In addition
      to investigating the key factors affecting solubility, the hygroscopicity of the
      crystalline salts was studied to determine which solid-state and counterion
      properties might be responsible for enhancements in moisture uptake, thus
      providing the potential for adverse chemical stability. Multivariate principal
      components and partial least squares projection to latent structures analyses
      were performed in an attempt to establish predictive models capable of describing
      the relationships between these characteristics and both measured and calculated
      properties of the counterion and salt. Some success was achieved with respect to
      modeling crystalline salt solubility and the glass transition temperature of the
      amorphous salts. Through the modeling, insight into the relative importance of
      various descriptors on salt properties was achieved. The solid-state properties
      of crystalline and amorphous salts of procaine are highly dependent on the nature
      of the counterion. Important properties including aqueous solubility, melting
      point, hygroscopicity, and glass transition temperature were found to vary
      considerably between the different salts.

PMID- 20680708
TI  - Optimization of PEGylation conditions for BSA nanoparticles using response
      surface methodology.
AB  - Chemical coupling of polyethylene glycol (PEG) to proteins or particles
      (PEGylation), prolongs their circulation half-life by greater than 50-fold,
      reduces their immunogenicity, and also promotes their accumulation in tumors due
      to enhanced permeability and retention effect. Herein, phase separation method
      was used to prepare bovine serum albumin (BSA) nanoparticles. PEGylation of BSA
      nanoparticles was performed by SPA activated mPEG through their free amino
      groups. Effect of process variables on PEGylation efficiency of BSA nanoparticles
      was investigated and optimized through response surface methodology with the
      amount of free amino groups as response. Optimum conditions was found to be 32.5
      g/l of PEG concentration, PEG-nanoparticle incubation time of 10 min, incubation
      temperature of 27 degrees C, and pH of 7 for 5 mg of BSA nanoparticles in 1 mL
      phosphate buffer. Analysis of data showed that PEG concentration had the most
      noticeable effect on the amount of PEGylated amino groups, but pH had the least.
      Mean diameter and zeta potential of PEGylated nanoparticles under these
      conditions were 217 nm and -14 mV, respectively. In conclusion, PEGylated
      nanoparticles demonstrated reduction of the negative surface charge compared to
      the non modified particles with the zeta potential of -31.7 mV. Drug release from
      PEGylated nanoparticles was almost slower than non-PEGylated ones, probably due
      to existence of a PEG layer around PEGylated particles which makes an extra
      resistance in opposition to drug diffusion.

PMID- 20680709
TI  - Small molecule screening in zebrafish.
AB  - Small molecule screens have become useful tools in ongoing efforts to understand
      complex biologic systems and disease states. These screens can identify compounds
      that specifically affect signaling pathways, development, and disease processes.
      The zebrafish Danio rerio has increasingly been used as a whole organism model in
      which to perform such functional small molecule screens. Here, we review recent
      advances in screening approaches that focus on modulation of developmental
      processes and signaling pathways, along with suppressor screens of disease
      models. The identification of small molecule targets continues to be a challenge,
      and several recent approaches to this problem are discussed. The promise of
      chemical screens in zebrafish to identify novel biologic probes and therapeutic
      compounds continues to drive this rapidly growing field.

PMID- 20680710
TI  - The incidence of hypoxemia during surgery: evidence from two institutions.
AB  - PURPOSE: The incidence of hypoxemia in patients undergoing surgery is largely
      unknown and may have a clinical impact. The objective of this study was to
      determine the incidence of intraoperative hypoxemia in a large surgical
      population. METHODS: We performed a retrospective study of electronically
      recorded pulse oximetry data obtained from two large academic medical centres.
      All adults (age >= 16 yr) undergoing non-cardiac surgery during a three-year
      period at the two hospitals were included in the analysis. Our main outcome
      measure was the percentage of patients with episodes of hypoxemia (SpO(2) < 90)
      or severe hypoxemia (SpO(2) <= 85) for two minutes or longer during the
      intraoperative period (induction of anesthesia, surgery, and emergence). RESULTS:
      We evaluated 95,407 electronic anesthesia records at the two hospitals. During
      the intraoperative period, 6.8% of patients had a hypoxemic event, and 3.5% of
      patients had a severely hypoxemic event of two consecutive minutes or longer.
      Seventy percent of the hypoxemic episodes occurred during either induction or
      emergence- time periods that represent 21% of the total intraoperative time. From
      induction to emergence, one episode of hypoxemia occurred every 28.9 hr, and one
      episode of severe hypoxemia occurred every 55.7 hr of intraoperative time.
      CONCLUSION: Despite advances in monitoring technology, hypoxemia continues to
      occur commonly in the operating room and may be a serious safety concern because
      of its potential impact on end organ function and long-term outcomes. Further
      studies are needed to improve our understanding of the clinical impact of
      intraoperative hypoxemia and the strategies that will be most useful in
      minimizing its occurrence.

PMID- 20680711
TI  - Length of lymphangiogenesis in the rectal tissues distal to rectal cancer.
AB  - To investigate the length of lymphangiogenesis in the rectal tissue distal to a
      rectal cancer and its effect on the resection margins of the rectum, 63 specimens
      of normal rectal tissue distal to the tumor were collected from the surgical
      resections of ten rectal cancer patients. The specimens were taken at 0.5-cm
      intervals between the distal end of tumor and the distal surgical margin. The
      mean amount of collected tissue in each patient was 6.3. The expression of VEGFR
      3 and Prox1 was measured in the specimens using real-time quantitative reverse
      transcription polymerase chain reaction. VEGFR-3 and Prox1 were expressed in all
      harvested tissues. There was a reduction of expression of VEGFR-3 (nine cases)
      and Prox1 (ten cases) from tissue adjacent to the rectal tumor to the distal
      resection margin of the rectum. A downward slope of the expression levels of
      VEGFR-3 and Prox1 in all cases was found at less than 3.0 cm distal to the tumor.
      The median VEGFR-3 expression level in the tissues within 1.5 cm adjacent to the
      rectal cancer was higher than in those tissues beyond 1.5 cm (P = 0.024). The
      median Prox1 expression level in the tissues within 1.0 cm distal to the rectal
      cancer was higher than in those tissues beyond 1.0 cm (P = 0.003).
      Lymphangiogenesis may facilitate the mural spread of cancer cells. The length of
      development of new lymphatics in the rectal wall distal to a rectal cancer may be
      less than 3.0 cm. Resection of a rectal cancer should routinely include 3.0 cm
      distal to the tumor to ensure adequate excision of tissue subject to
      lymphangiogenesis and potential mural spread of the tumor.

PMID- 20680712
TI  - Prognostic impact of ERbeta and MMP7 expression on overall survival in colon
      cancer.
AB  - Estrogen receptor beta (ERbeta) is the most highly expressed protein in patients
      with colon cancer. Matrix metalloproteinase 7 (MMP7) is consistently expressed
      throughout cancer progression. We have previously shown that endocrine therapy
      can inhibit MMP7 expression in colon cancer cells. In this study, we aim to
      identify the prognostic effects and correlation of ERbeta and MMP7 in the context
      of colon cancer. ERbeta and MMP7 levels were assessed by immunohistochemistry in
      normal mucosa and tumoral tissues from 423 patients with stage I-III colon
      cancer. The Cox proportional hazards regression model was applied to analyze the
      lifetime data, including overall survival (OS) and cause-specific survival (CSS).
      The 5-year survival rate was significantly higher in patients with high
      expression of nuclear ERbeta than in patients with low expression (84.3% vs.
      63.9%, respectively, p < 0.05). High expression of MMP7 was related to decreased
      OS (72% vs. 90%, respectively, p = 0.008) and 5-year survival (86.6% vs. 88.8%,
      respectively, p = 0.005) compared to patients with low expression of MMP7. In the
      subset of patients with high expression levels of tumoral nuclear ERbeta, high
      expression of MMP7 was related to OS and CSS among colon cancer patients with
      high expression of ERbeta. In conclusion, our results suggest that low expression
      of ERbeta was a risk factor in colon cancer, and high expression of MMP7 was an
      independent prognostic factor of ERbeta-positive patients with colon cancer.

PMID- 20680713
TI  - Sepsis and multiorgan dysfunction. Abstracts of the 4th International Congress of
      the German Sepsis Society. September 9-12, 2009. Weimar, Germany.

PMID- 20680714
TI  - [Not Available].

PMID- 20680715
TI  - [Not Available].

PMID- 20680716
TI  - [Not Available].

PMID- 20680717
TI  - [Not Available].

PMID- 20680718
TI  - [Not Available].

PMID- 20680719
TI  - [Not Available].

PMID- 20680720
TI  - [Not Available].

PMID- 20680721
TI  - [Not Available].

PMID- 20680722
TI  - [Not Available].

PMID- 20680723
TI  - Summaries of articles.

PMID- 20680724
TI  - [Not Available].

PMID- 20680726
TI  - Periodization of the east asian history of science.

PMID- 20680725
TI  - The Role of Maragha in the Development of Islamic Astronomy : A scientific
      revolution before the renaissance.

PMID- 20680727
TI  - [Not Available].

PMID- 20680729
TI  - [Not Available].

PMID- 20680728
TI  - A new view of scientific rationality.

PMID- 20680730
TI  - [Not Available].

PMID- 20680731
TI  - Summaries of articles.

PMID- 20680732
TI  - [Not Available].

PMID- 20680733
TI  - [Not Available].

PMID- 20680734
TI  - [Not Available].

PMID- 20680735
TI  - [Not Available].

PMID- 20680736
TI  - [Not Available].

PMID- 20680737
TI  - [Not Available].

PMID- 20680738
TI  - [Not Available].

PMID- 20680739
TI  - Summaries of articles.

PMID- 20680741
TI  - [Not Available].

PMID- 20680740
TI  - [Not Available].

PMID- 20680742
TI  - [Not Available].

PMID- 20680743
TI  - [Not Available].

PMID- 20680744
TI  - [Not Available].

PMID- 20680745
TI  - [Not Available].

PMID- 20680746
TI  - Summaries of articles.

PMID- 20680747
TI  - XVIII(th) International Congress of the History of ScienceHamburg and Munich
      Federal Republic of Germany1-9 August 1989.

PMID- 20680748
TI  - [Not Available].

PMID- 20680749
TI  - [Not Available].

PMID- 20680750
TI  - [Not Available].

PMID- 20680751
TI  - [Not Available].

PMID- 20680752
TI  - [Not Available].

PMID- 20680753
TI  - [Not Available].

PMID- 20680754
TI  - Summaries of articles.

PMID- 20680755
TI  - [Not Available].

PMID- 20680756
TI  - [Not Available].

PMID- 20680757
TI  - Crisis without revolution : The ideological watershed in Victorian England.

PMID- 20680758
TI  - [Not Available].

PMID- 20680759
TI  - [Not Available].

PMID- 20680760
TI  - Hermeneutics and cross-cultural communication in Science : The reception of
      Western Scientific Ideas in 19th-Century India.

PMID- 20680761
TI  - [Not Available].

PMID- 20680762
TI  - [Not Available].

PMID- 20680763
TI  - [Not Available].

PMID- 20680765
TI  - Summaries of articles.

PMID- 20680764
TI  - [Not Available].

PMID- 20680766
TI  - The history of ideas revisited.

PMID- 20680769
TI  - Commentary on greene and mayr.

PMID- 20680767
TI  - The death of Darwin?

PMID- 20680768
TI  - [Not Available].

PMID- 20680770
TI  - [Not Available].

PMID- 20680771
TI  - [Not Available].

PMID- 20680772
TI  - [Not Available].

PMID- 20680773
TI  - [Not Available].

PMID- 20680775
TI  - Summaries of articles.

PMID- 20680774
TI  - [Not Available].

PMID- 20680776
TI  - [Not Available].

PMID- 20680777
TI  - [Not Available].

PMID- 20680778
TI  - [Not Available].

PMID- 20680779
TI  - [Not Available].

PMID- 20680780
TI  - [Not Available].

PMID- 20680782
TI  - Second International Conference of the International Society for the Study of
      European Ideas (ISSEI) : Comparative history of European Nationalism (on the eve
      of 1992).

PMID- 20680781
TI  - [Not Available].

PMID- 20680783
TI  - [Not Available].

PMID- 20680785
TI  - [Not Available].

PMID- 20680784
TI  - [Not Available].

PMID- 20680786
TI  - Summaries of articles.

PMID- 20680787
TI  - [Not Available].

PMID- 20680788
TI  - Sctentific thought and its meaning for religion : The impact of French science on
      British Natural Theology, 1827-1859.

PMID- 20680789
TI  - [Not Available].

PMID- 20680790
TI  - [Not Available].

PMID- 20680791
TI  - [Not Available].

PMID- 20680792
TI  - [Not Available].

PMID- 20680794
TI  - Summaries of articles.

PMID- 20680793
TI  - [Not Available].

PMID- 20680795
TI  - [Not Available].

PMID- 20680796
TI  - [Not Available].

PMID- 20680797
TI  - [Not Available].

PMID- 20680798
TI  - [Not Available].

PMID- 20680799
TI  - [Not Available].

PMID- 20680800
TI  - [Not Available].

PMID- 20680801
TI  - Summaries of articles.

PMID- 20680802
TI  - Angiogenesis and the tumor vasculature as antitumor immune modulators: the role
      of vascular endothelial growth factor and endothelin.
AB  - Cancer immunotherapies have yielded promising results in recent years, but new
      approaches must be utilized if more patients are to experience the benefits of
      these therapies. Angiogenesis and the tumor endothelium confer unique immune
      privilege to a growing tumor, with significant effects on diverse immunological
      processes such as hematopoietic cell maturation, antigen presentation, effector T
      cell differentiation, cytokine production, adhesion, and T cell homing and
      extravasation. Here, we review the role of angiogenesis and the tumor endothelium
      on regulation of the antitumor immune response. We place particular emphasis on
      the role of vascular endothelial growth factor (VEGF) in the suppression of
      numerous immunological processes that control tumor progression. Further, we
      describe the unique crosstalk between the VEGF and endothelin systems, and how
      their interactions may shape the antitumor immune response. These insights
      establish new targets for combinatorial approaches to modify existing cancer
      immunotherapies.

PMID- 20680803
TI  - Small-molecule modulators of c-Myc/Max and Max/Max interactions.
AB  - The transcription factor c-Myc is overexpressed in many tumors in human beings
      and has been identified as a highly promising target for cancer therapy. Most
      biological functions of c-Myc require heterodimerization with its activation
      partner Max. Inhibition of the protein-protein interactions between c-Myc and Max
      by small molecules has been shown to be a feasible and powerful approach toward
      the inhibition of c-Myc functions. More recently, stabilization of Max homodimers
      to reduce the amount of Max available for activating c-Myc has also been
      demonstrated to counteract Myc activity. This review summarizes our current
      knowledge on small organic molecules that inhibit c-Myc by modulating protein
      protein interactions relevant for the biological function of this important
      oncoprotein.

PMID- 20680804
TI  - Concepts and ways to amplify the antitumor immune response.
AB  - In this chapter, a detailed description of how the innate and adaptive immune
      responses interact with malignant cells is presented. In addition, we discuss how
      developing tumors establish themselves, and how they benefit on one hand and
      organize their defense against the immune system on the other hand. New data from
      three tumor model systems in mice are discussed; in particular, the intricate
      interactions between the immune cells and the tumor cells are highlighted. With
      the present data and knowledge, we conclude that a first prerequisite for the
      combat against tumors is the activation of the innate immune system via external
      danger signals or damage signals and internal danger signals. The second
      prerequisite for efficient tumor cell eradication is combined therapeutic
      approaches of physical, chemical, pharmacological, and immunological origin.
      Finally, we propose new ways for further investigation of the relationship
      linking tumor cells and our defense system. It appears mandatory to understand
      how the malignant cells render the adaptive immune cells tolerant instead of
      turning them into aggressive effectors and memory cells. Perhaps, the most
      important thing, for immunologists and clinicians, to understand is that tumor
      cells must not be viewed just as antigens but much more.

PMID- 20680805
TI  - Immunoregulatory roles for fc receptor-like molecules.
AB  - Fc receptor-like (FCRL) molecules comprise a family of imunoregulatory
      transmembrane proteins that are preferentially, but not exclusively expressed on
      B lineage cells. A strong regulatory potential on B cell activation has been
      characterized for the different FCRL proteins, but their biological roles are
      just beginning to be elucidated. We review recent advances in the understanding
      of FCRL1-6 expression and function, and indicate their potential roles in the
      pathogenesis of immunodeficiencies, lymphoid malignancies and autoimmune
      diseases.

PMID- 20680806
TI  - TGF-beta function in immune suppression.
AB  - Transforming growth factor-beta (TGF-beta) has been shown to play an essential
      role in establishing immunological tolerance, yet recent studies have revealed
      the pro-inflammatory roles of TGF-beta in inflammatory responses. TGF-beta
      induces Foxp3-positive regulatory T cells (iTregs), while in the presence of IL
      6, it induces pathogenic IL-17 producing Th17 cells. TGF-beta inhibits the
      proliferation of T cells as well as cytokine production via Foxp3-dependent and
      independent mechanisms. On the one hand, little is known about molecular
      mechanisms involved in immune suppression via TGF-beta; however, recent studies
      suggest that Smad2 as well as Smad3 play essential roles in Foxp3 induction and
      cytokine suppression, whereas Th17 differentiation is promoted via the Smad
      independent pathway. Mutual suppression of signaling between TGF-beta and
      inflammatory cytokines has been shown to be necessary for the balance of immunity
      and tolerance.

PMID- 20680807
TI  - FcgammaRs in health and disease.
AB  - Genetic defects affecting the humoral immune response and especially the
      production of antibodies of the immunoglobulin G (IgG) isotype result in a
      heightened susceptibility to infections. Studies over the last years have
      demonstrated the crucial role of Fc-receptors for IgG (FcgammaRs) widely
      expressed on innate immune effector cells in mediating the protective function of
      IgG. During the last years, additional ligands interacting with FcgammaRs as well
      as additional receptors binding to IgG glycosylation variants have been
      identified. In this review, we discuss how the interaction of these different
      ligands with classical and novel Fcgamma-receptors influences the immune response
      and which strategies microorganisms have developed to prevent them.

PMID- 20680808
TI  - Inhibitory Ly49 receptors on mouse natural killer cells.
AB  - The Ly49 receptors, which are expressed in a stochastic manner on subsets of
      murine natural killer (NK) cells, T cells, and other cells, are encoded by the
      Klra gene family and include receptors with either inhibitory or activating
      function. All of the inhibitory Ly49 receptors are characterized by an
      immunoreceptor tyrosine-based inhibitory motif in their cytoplasmic domain, which
      upon phosphorylation recruits tyrosine or lipid phosphatases to dampen signals
      transmitted through other activating receptors. Most of the inhibitory Ly49
      receptors recognize polymorphic epitopes on major histocompatibility complex
      (MHC) class I proteins as ligands. Here, we review the polymorphism, ligand
      specificity, and signaling capacity of the inhibitory Ly49 receptors and discuss
      how these molecules regulate NK cell development and function.

PMID- 20680809
TI  - Stem cells for myocardial repair and regeneration: where are we today?
AB  - An overview for the use of stem cells for myocardial repair and regeneration is
      provided. The overview provides the rationale for use of stem cells in myocardial
      repair. Potential stem cell types and technological challenges are highlighted.

PMID- 20680810
TI  - Bone marrow-derived endothelial progenitor cells: isolation and characterization
      for myocardial repair.
AB  - Vascular regeneration with bone marrow (BM) stem/progenitor cells is one of the
      promising therapeutic strategies for myocardial repair in cardiovascular
      diseases. Endothelial progenitor cells (EPCs) have demonstrated the beneficial
      effects on ischemia-induced myocardial damage promoting angiogenesis in ischemic
      tissue. Isolation of EPCs from BM or peripheral blood is required for the cell
      based therapeutic approach. Among a variety of EPC isolation methods,
      specifically in the case of experimental animal models, we have shown our
      recently developed mouse-cultured EPC isolation protocol, which is viable for
      obtaining enough number of viable cells for not only in vitro but also in vivo
      experiments, and the protocol for human CD34(+) cell (EPC rich cell population)
      isolation from peripheral blood and characterization by fluorescence-activated
      sorting (FACS) system.

PMID- 20680811
TI  - Umbilical cord blood stem cells for myocardial repair and regeneration.
AB  - Cardiovascular disease remains a major cause of morbidity and mortality with
      substantial economic cost. There remains a need for therapeutic improvement for
      patients refractory to revascularization and those who redevelop occlusions
      following revascularization. Early evidence linked age-associated reductions in
      the levels of circulating marrow-derived hematopoietic stem cells (HSC),
      characterized by expression of early HSC markers CD133 and CD34, with the
      occurrence of cardiovascular events and associated death. Heart tissue has the
      endogenous ability to regenerate through the activation of resident cardiac stem
      cells or through recruitment of a stem cell population from other tissues, such
      as bone marrow. A number of clinical trials have utilized patient-derived
      autologous bone marrow-derived cells or whole BM uncultured mononuclear cells
      (MNC) infused or injected locally to augment angiogenesis. In most cases of
      treating animal models with human cells, the frequency of stem cell engraftment,
      the subsequent number of newly generated cardiomyocytes and vascular cells, and
      the augmentation of endogenous microvascular collateralization, either by
      deposition, transdifferentiation, and/or by cell fusion, appear to be too low to
      explain the significant cardiac improvement. Initially, it was hypothesized that
      cell therapy may work by cell replacement mechanisms, but recent evidence
      suggests alternatively that cell therapy works by providing trophic support to
      the injured tissues. An alternative hypothesis is that the transplanted stem
      cells release soluble cytokines and growth factors (i.e., paracrine factors) that
      function in a paracrine fashion, contributing to cardiac repair and regeneration
      by inducing cytoprotection and neovascularization. Another hypothesis which may
      also be operative is that cell therapy may mediate endogenous regeneration by the
      activation of resident cardiac stem cell. Well-established clinical trials have
      used cord blood for the treatment of hematological malignances (e.g., leukemia,
      lymphoma, myeloma) and nonmalignancies (e.g., in born errors of metabolism,
      sickle cells anemia, autoimmune diseases), but further advances in other areas of
      regenerative medicine (e.g., cardiac repair) will directly benefit with the use
      of cord blood. These clinical outcomes demonstrate that effector cells may be
      delivered by an allogeneic approach, where strict tissue matching may not be
      necessary and treatment may be achieved by making use of the trophic support
      capability of cell therapy and not by a cell replacement mechanism.

PMID- 20680812
TI  - Isolation of resident cardiac progenitor cells by Hoechst 33342 staining.
AB  - Cardiac resident stem/progenitor cells are critical to the cellular and
      functional integrity of the heart by maintaining myocardial cell homeostasis.
      Given their central role in myocardial biology, resident cardiac progenitor cells
      have become a major focus in cardiovascular research. Identification of putative
      cardiac progenitor cells within the myocardium is largely based on the presence
      or absence of specific cell surface markers. Additional purification strategies
      take advantage of the ability of stem cells to efficiently efflux vital dyes such
      as Hoechst 33342. During fluoresence activated cell sorting (FACS) such Hoechst
      extruding cells appear to the side of Hoechst-dye retaining cells and have thus
      been termed side population (SP) cells. We have shown that cardiac SP cells that
      express stem cell antigen 1 (Sca-1) but not CD31 are cardiomyogenic, and thus
      represent a putative cardiac progenitor cell population. This chapter describes
      the methodology for the isolation of resident cardiac progenitor cells utilizing
      the SP phenotype combined with stem cell surface markers.

PMID- 20680813
TI  - Mesenchymal stem cell therapy for cardiac repair.
AB  - Stem cell therapy for repair of damaged cardiac tissue is an attractive option to
      improve the health of the growing number of heart failure patients. Mesenchymal
      stem cells (MSCs) possess unique properties that may make them a better option
      for cardiac repair than other cell types. Unlike other adult stem cells, they
      appear to escape allorecognition by the immune system and they have immune
      modulating properties, thus making it possible to consider them for use as an
      allogeneic cell therapy product. There is a large and growing body of preclinical
      and early clinical experience with MSC therapy that shows great promise in
      realizing the potential of stem cell therapy to effect repair of damaged cardiac
      tissue. This review discusses the mechanism of action of MSC therapy and
      summarizes the current literature in the field.

PMID- 20680814
TI  - Methods for human embryonic stem cells derived cardiomyocytes cultivation,
      genetic manipulation, and transplantation.
AB  - A decade has passed since the initial derivation of human embryonic stem cells
      (hESC). The ensuing years have witnessed a significant progress in the
      development of methodologies allowing cell cultivation, differentiation, genetic
      manipulation, and in vivo transplantation. Specifically, the potential to derive
      human cardiomyocytes from the hESC lines, which can be used for several basic and
      applied cardiovascular research areas including in the emerging field of cardiac
      regenerative medicine, attracted significant attention from the scientific
      community. This resulted in the development of protocols for the cultivation of
      hESC and their successful differentiation toward the cardiomyocyte lineage fate.
      In this chapter, we will describe in detail methods related to the cultivation,
      genetic manipulation, selection, and in vivo transplantation of hESC-derived
      cardiomyocytes.

PMID- 20680815
TI  - Experimental cell transplantation therapy in rat myocardial infarction model
      including nude rat preparation.
AB  - As a novel potential therapeutic strategy for cardiac disease, cell
      transplantation therapy has been extensively investigated in experimental studies
      and clinical trials. Although encouraging results have been demonstrated, a
      number of critical questions still remain to be answered. For example, what kind
      of stem cell and how many cells should be used; what is the best time for cell
      transplantation after acute myocardial infarction; which delivery approach is
      better, intravenous injection or direct intramyocardial injection?
      Transplantation of cells derived from human tissues into experimental animals may
      elicit an immune rejection. Immunodeficient nude rats provide a useful myocardial
      infarction model for cell transplantation therapy studies. We introduce our
      detailed methods of direct intramyocardial injection of immature heart cells and
      stem cells into the myocardial infarction region of rats and nude rats. Careful
      maintenance under aseptic conditions and proper surgical technique are essential
      to improve the survival of immunodeficient rats after surgery.

PMID- 20680816
TI  - Large animal model of heart failure for assessment of stem cells.
AB  - The field of stem cell biology and regenerative medicine is rapidly moving toward
      translation to clinical practice, and in doing so has become more dependent on
      animal donors and hosts for generating cellular reagents and assaying their
      potential therapeutic efficacy in models of human disease. Animal models of
      cardiovascular disease have proved critically important for the discovery of
      pathophysiological mechanisms and for the advancement of diagnosis and therapy.
      They offer a number of advantages; principally the availability of adequate
      healthy controls and the absence of confounding factors such as marked
      differences in age, concomitant pathologies, and pharmacological treatments. Over
      the past 30 years, investigators have developed numerous small and large animal
      models to study heart failure (HF). However, to translate discoveries from basic
      science into medical applications, research in large animal models becomes a
      necessary step. Intracoronary microembolizations-induced HF in dogs is an
      excellent large animal model of congestive HF for the assessment of
      pharmacological drugs, medical devices, and stem cells.

PMID- 20680817
TI  - Histopathologic assessment of myocardial regeneration.
AB  - Cardiac regeneration in the form of cell-based therapy offers hope of becoming
      the breakthrough technology that transforms the state of cardiac medicine. Before
      attempting to develop the techniques to assess the effectiveness of myocardial
      regeneration in humans, researchers must have at least a basic understanding of
      the human heart in its embryonic, normal, and diseased states. To this end, we
      provide an overview of the histology of the heart, including the current theories
      on normal embryogenesis and the histology of normal and ischemic myocardium as
      visualized by pathologists. Knowledge of the cellular constituents, including the
      controversial existence of resident cardiac stem and/or progenitor cells, and
      their actions and interactions in the normal state and under the conditions of
      myocardial ischemia is also crucial before embarking on the quest for cardiac
      regeneration. Despite widespread optimism in the success of cell-based therapy,
      inherent difficulties remain in the identification of effective cell populations
      proposed for cell-based therapy in the human heart.

PMID- 20680818
TI  - Assessment of myocardial angiogenesis and vascularity in small animal models.
AB  - Therapies that aim to prevent myocardial tissue from dying or to regenerate new
      myocardium all rely on the preservation or growth of a functional vasculature.
      The amount of blood that supplies the myocardium is dependent on the number and
      nature of the microvessels, as well as the ability of the arteries to supply
      blood and the veins to remove it. All of these factors can be assessed when
      success of an experimental therapy is being evaluated. Different kinds of
      information can be obtained from these different parameters, and it is important
      to understand what each one involves and how it can be misinterpreted. This
      chapter describes the various approaches to the assessment of vascularity in the
      heart with a focus on small animal models, dealing both with those approaches
      that are purely histological endpoint studies and those that are functional
      measurements in living animals.

PMID- 20680819
TI  - Superparamagnetic iron oxide labeling of stem cells for MRI tracking and delivery
      in cardiovascular disease.
AB  - In the mid-1980s, iron oxide nanoparticles were developed as contrast agents for
      diagnostic imaging. In the last two decades, established methods to label cells
      with superparamagnetic iron oxides (SPIOs) have been developed to aid in targeted
      delivery and tracking of stem cell therapies. The surge in cellular therapy
      clinical trials for cardiovascular applications has seen a similar rise in the
      number of preclinical animal studies of SPIO-labeled stem cells in an effort to
      understand the mechanisms of cardiovascular regenerative therapy and stem cell
      biodistribution. The adoption of a limited number of methods of direct labeling
      of stem cells with SPIOs is due in large part to the desire to rapidly translate
      these techniques to clinical trials. In this review, we will outline the most
      commonly adopted methods for iron oxide labeling of stem cells for cardiovascular
      applications and describe strategies for magnetic resonance imaging (MRI) of
      magnetically labeled cells in the heart.

PMID- 20680820
TI  - Embryonic stem cell biology: insights from molecular imaging.
AB  - Embryonic stem (ES) cells have therapeutic potential in disorders of cellular
      loss such as myocardial infarction, type I diabetes and neurodegenerative
      disorders. ES cell biology in living subjects was largely poorly understood until
      incorporation of molecular imaging into the field. Reporter gene imaging works by
      integrating a reporter gene into ES cells and using a reporter probe to induce a
      signal detectable by normal imaging modalities. Reporter gene imaging allows for
      longitudinal tracking of ES cells within the same host for a prolonged period of
      time. This has advantages over postmortem immunohistochemistry and traditional
      imaging modalities. The advantages include expression of reporter gene is limited
      to viable cells, expression is conserved between generations of dividing cells,
      and expression can be linked to a specific population of cells. These advantages
      were especially useful in studying a dynamic cell population such as ES cells and
      proved useful in elucidating the biology of ES cells. Reporter gene imaging
      identified poor integration of differentiated ES cells transplanted into host
      tissue as well as delayed donor cell death as reasons for poor long-term survival
      in vivo. This imaging technology also confirmed that ES cells indeed have
      immunogenic properties that factor into cell survival and differentiation.
      Finally, reporter gene imaging improved our understanding of the neoplastic risk
      of undifferentiated ES cells in forming teratomas. Despite such advances, much
      remains to be understood about ES cell biology to translate this technology to
      the bedside, and reporter gene imaging will certainly play a key role in
      formulating this understanding.

PMID- 20680821
TI  - Genetic fate-mapping for studying adult cardiomyocyte replenishment after
      myocardial injury.
AB  - Mounting evidence suggests the regenerative potential of the mammalian heart.
      Nevertheless, the contribution of endogenous stem or precursor cells to adult
      cardiac regeneration upon myocardial injuries remains unclear. We hereby describe
      a genetic fate-mapping approach to study adult cardiomyocyte replenishment after
      myocardial injury. Using double transgenic MerCreMer-ZEG mice, the fate of adult
      cardiomyocytes can be tracked by the expression of green fluorescence protein
      (GFP) specifically induced in cardiomyocytes. Upon experimental myocardial
      infarction, a reduction in GFP expression in the myocardium is observed,
      indicating the refreshment of cardiomyocytes by endogenous stem or precursor
      cells.

PMID- 20680822
TI  - In vitro electrophysiological mapping of stem cells.
AB  - The use of stem cells for cardiac regeneration is a revolutionary, emerging
      research area. For proper function as replacement tissue, stem cell-derived
      cardiomyocytes (SC-CMs) must electrically couple with the host cardiac tissue.
      Electrophysiological mapping techniques, including microelectrode array (MEA) and
      optical mapping, have been developed to study cardiomyocytes and cardiac cell
      monolayers, and these can be applied to study stem cells and SC-CMs. MEA
      recordings take extracellular measurements at numerous points across a small area
      of cell cultures and are used to assess electrical propagation during cell
      culture. Optical mapping uses fluorescent dyes to monitor electrophysiological
      changes in cells, most commonly transmembrane potential and intracellular
      calcium, and can be easily scaled to areas of different sizes. The materials and
      methods for MEA and optical mapping are presented here, together with detailed
      notes on their use, design, and fabrication. We also provide examples of voltage
      and calcium maps of mouse embryonic stem cell-derived cardiomyocytes (mESC-CMs),
      obtained in our laboratory using optical mapping techniques.

PMID- 20680823
TI  - Assessment of cardiac conduction: basic principles of optical mapping.
AB  - Extracellular recordings acquired from electrodes placed on the surface of
      cardiac tissue have traditionally been used to study the electrophysiological
      properties of the tissue. While this technique has been used in several studies
      that have increased our understanding of cardiac arrhythmias and action potential
      propagation, there are several limitations that have prevented us from seeing a
      bigger picture of arrhythmia mechanisms. These limitations include the limited
      number of electrodes and unstable recordings. Optical mapping was developed to
      increase the temporal and spatial resolution over traditional electrode
      recordings and ultimately the accuracy of the data analysis. This technology
      involves using a voltage-sensitive dye that binds to the cell membrane. The
      fluorescence changes of the dye have a linear relationship to the action
      potential changes of the cell membrane. These fluorescent changes can then be
      detected by a photodiode array, a CCD camera or a CMOS camera. This will allow
      the recording of the action potential in hundreds to thousands of different sites
      simultaneously. Presented in this chapter are the materials and hardware needed
      along with step-by-step instructions on setup and techniques used in optical
      mapping for larger tissue preparations.

PMID- 20680824
TI  - Surface patterning for generating defined nanoscale matrices.
AB  - While stem cells in culture have been predominately controlled through the
      addition of soluble factors to the media, the impact of the extracellular matrix
      on stem cell renewal and differentiation has recently come to the forefront. In
      vivo, cells adhere and respond to cues that are on the nanoscale, thus the
      presentation of extracellular matrix components on this scale is critical to
      mimicking the in vivo environment. We have developed a highly flexible
      nanopatterning technique, employing protein and peptide reactive polymers and
      electron beam lithography, which can be utilized for studying matrix effects on
      stem cell renewal and differentiation.

PMID- 20680825
TI  - The generation of zinc finger proteins by modular assembly.
AB  - The modular assembly (MA) method of generating engineered zinc finger proteins
      (ZFPs) was the first practical method for creating custom DNA-binding proteins.
      As such, MA has enabled a vast exploration of sequence-specific methods and
      reagents, ushering in the modern era of zinc finger-based applications that are
      described in this volume. The first zinc finger nuclease to cleave an endogenous
      site was created using MA, as was the first artificial transcription factor to
      enter phase II clinical trials. In recent years, other excellent methods have
      been developed that improved the affinity and specificity of the engineered ZFPs.
      However, MA is still used widely for many applications. This chapter will
      describe methods and give guidance for the creation of ZFPs using MA. Such ZFPs
      might be useful as starting materials to perform other methods described in this
      volume. Here, we also describe a single-strand annealing recombination assay for
      the initial testing of zinc finger nucleases.

PMID- 20680826
TI  - Engineering single Cys2His2 zinc finger domains using a bacterial cell-based two
      hybrid selection system.
AB  - Individual synthetic Cys2His2 zinc finger domains with novel DNA-binding
      specificities can be identified from large randomized libraries using selection
      methodologies such as phage display. We have previously demonstrated that a
      bacterial cell-based two-hybrid system is at least as effective as phage display
      for selecting zinc fingers with desired specificities from such libraries. In
      this chapter we provide updated, detailed protocols for performing zinc finger
      selections using the bacterial two-hybrid system.

PMID- 20680827
TI  - Bipartite selection of zinc fingers by phage display for any 9-bp DNA target
      site.
AB  - Phage display has been used to engineer DNA-binding proteins with new sequence
      specificities, which has allowed applications in the blockage or enhancement of
      gene expression as well as targeting specific sites on DNA for methylation,
      recombination, and cleavage. To effectively and quickly conduct selections that
      consider the synergistic mode of DNA binding by zinc fingers, Isalan and Choo in
      Aaron Klug's lab devised a bipartite phage display approach that enables
      selection and recombination of variants of zinc finger DNA-binding domains from a
      pair of premade complementary phage libraries for any given 9-bp DNA sequence.
      The bipartite phage display has the advantage of rapid, high-throughput selection
      of sequence-specific zinc finger DNA-binding domains for use in diverse
      applications of expression control and gene targeting.

PMID- 20680828
TI  - Structure-based DNA-binding prediction and design.
AB  - Structure-based DNA-binding prediction is a powerful tool to infer protein
      binding sites and design new specificities. It can limit experiments in scope and
      help focus them toward candidates with higher chances of success. The zinc finger
      domain is an excellent scaffold for design due to its small and robust fold and
      relatively simple interaction pattern. It presents some degree of modularity, and
      modeling can be used to guide experiments and help increase zinc finger module
      libraries. In this chapter we present a fast and simple but still powerful method
      for predicting and designing DNA-binding specificities applied to C(2)H(2) zinc
      finger proteins, based on FoldX, a semiautomatic protein design tool. Given a
      template structure, this method generates candidate mutants for a given target
      DNA sequence selected by energetic criteria.

PMID- 20680829
TI  - Generation of cell-permeable artificial zinc finger protein variants.
AB  - Designed or artificial zinc finger proteins (ZFPs) are one of the most promising
      DNA-binding proteins that target genomic sequences of interest in vitro and in
      vivo. Conjugation of other functional domains such as transcriptional regulatory
      domains and endonucleases to ZFPs provided powerful molecular tools to modulate
      endogenous gene expression and genetic information. These ZFP variants have been
      introduced into cells as DNA-encoding ZFP variants by using plasmids or viral
      vectors. As an alternative delivery method of ZFP variants, we developed cell
      permeable ZFP variants by fusing cell-penetrating peptides to ZFP variants. We
      will describe how to generate cell-permeable artificial ZFP variants and how to
      examine the cell permeabilities by immunofluorescent staining.

PMID- 20680830
TI  - Inhibition of viral transcription using designed zinc finger proteins.
AB  - Currently available therapeutics for hepatitis B virus (HBV) infection have
      limited effectiveness in patients and often do not clear HBV from the liver due
      to the persistence of the stable, double-stranded (ds) DNA genome of HBV. By
      designing zinc finger proteins (ZFPs) to bind the dsDNA genome of a model virus,
      duck HBV (DHBV), we were able to inhibit viral transcription, and subsequently,
      viral protein and progeny production. This inhibition is likely due to
      competition for DNA binding sites between the ZFPs and transcription factors, and
      interference with read-through transcription by RNA polymerase across the ZFP
      binding region. Taking into account some design considerations, this method of
      inhibiting viral transcription can be applied to other viral infections where
      viral dsDNA occurs.

PMID- 20680831
TI  - Modulation of gene expression using zinc finger-based artificial transcription
      factors.
AB  - Artificial transcription factors (ATFs) consist of a transcriptional effector
      domain fused to a DNA-binding domain such as an engineered zinc finger protein
      (ZFP). Depending on the effector domain, ATFs can up- or downregulate gene
      expression and thus represent powerful tools in biomedical research and allow
      novel approaches in clinical practice. Here, we describe the construction of ATFs
      directed against the promoter of the epithelial cell adhesion molecule and
      against the promoter of the RNA component of telomerase. Methods to assess DNA
      binding of the engineered ZFP as well as to determine and improve the cellular
      effect of ATFs on (endogenous) promoter activity are described.

PMID- 20680832
TI  - Construction of combinatorial libraries that encode zinc finger-based
      transcription factors.
AB  - Combinatorial retroviral libraries of zinc finger transcription factors (ZF-TFs)
      can be constructed that encode tens of thousands of different, multi-finger zinc
      finger proteins (ZFPs) with distinct DNA-binding specificities, each of which is
      fused to a transcriptional activation or repression domain. Individual zinc
      fingers (ZFs) recognize their target DNA subsites and retain their binding
      specificities in the context of artificially constructed multi-finger ZFPs.
      Because of this modular nature, expression libraries that specify diverse multi
      finger ZF-TFs can be created by the combinatorial stitching together of
      individual modules in a pool of single-ZF-encoding DNA segments. When these
      libraries are introduced into cells, the encoded ZF-TFs are expressed and can
      then activate or repress the transcription of endogenous target genes. Ideally,
      the ZF-TF-encoding retroviral vectors in the library enter cells randomly at a
      ratio of approximately 1 per cell. As a result, individual cells express
      different ZF-TFs and thus display distinct phenotypical changes. Using an
      appropriate screening or selection method, one can isolate clonal cells that
      display phenotypes of interest. One can then identify the ZF-TFs responsible for
      the phenotypes and, ultimately, the genes that are targeted by the selected ZF
      TFs. Here, we provide protocols for the preparation of retroviral libraries that
      encode ZF-TFs for use in mammalian cells.

PMID- 20680833
TI  - Silencing of gene expression by targeted DNA methylation: concepts and
      approaches.
AB  - Targeted DNA methylation is a novel and attractive approach for stable silencing
      of gene expression by epigenetic mechanisms. The potential applications of this
      concept include cancer treatment, treatment of viral infections and, in general,
      treatment of any disease that could be attenuated by the stable repression of
      known target genes. We review the literature on targeted DNA methylation and gene
      silencing, summarize the achievements and the challenges that remain, and discuss
      technical issues critical for this approach.

PMID- 20680834
TI  - Remodeling genomes with artificial transcription factors (ATFs).
AB  - Chromatin structure plays a pivotal role in defining which regions of the genome
      are accessible for effective transcription. Chromatin-remodeling agents are able
      to relax this structure, facilitating the access of transcription factors into
      the DNA. Herein, we describe a new method, which combines artificial
      transcription factors (ATFs) and chromatin-remodeling agents to specifically
      reactivate silenced regions of the genome and reprogram cellular phenotypes.

PMID- 20680835
TI  - Transgenic mice expressing an artificial zinc finger regulator targeting an
      endogenous gene.
AB  - Zinc finger (ZF) proteins belonging to the Cys2-His2 class provide a simple and
      versatile framework to design novel artificial transcription factors (ATFs)
      targeted to the desired genes. Our work is based on ZF ATFs engineered to up
      regulate the expression level of the dystrophin-related gene utrophin in Duchenne
      muscular dystrophy (DMD). In particular, on the basis of the "recognition code"
      that defines specific rules between zinc finger primary structure and potential
      DNA-binding sites we engineered and selected a new family of artificial
      transcription factors, whose DNA-binding domain consists in a three zinc finger
      peptide called "Jazz." Jazz protein binds specifically the 9 bp DNA sequence
      (5(')-GCT-GCT-GCG-3(')) present in the promoter region of both the human and
      mouse utrophin gene. We generated a transgenic mouse expressing Jazz protein
      fused to the strong transcriptional activation domain VP16 and under the control
      of the muscle specific promoter of the myosin light chain gene. Vp16-Jazz mice
      display a strong up-regulation of the utrophin at both mRNA and protein levels.
      To our knowledge, this represents the first example of a transgenic mouse
      expressing an artificial gene coding for a zinc finger-based transcription
      factor.

PMID- 20680836
TI  - Artificial zinc finger nucleases for DNA cloning.
AB  - DNA cloning is fundamental for modern cell research and biotechnology. Various
      restriction enzymes have been isolated, characterized, and purified to facilitate
      the digestion and ligation of DNA molecules of different origins. Nevertheless,
      the very small numbers of enzymes capable of digesting novel and long DNA
      sequences and the tedious and nearly impossible task of re-engineering existing
      enzymes with novel specificities greatly limit the use of restriction enzymes for
      the construction of complex and long DNA molecules. Zinc finger nucleases (ZFNs) 
      hybrid restriction enzymes that can be tailor made for the digestion of both
      native and artificial DNA sequences - offer a unique opportunity for expanding
      the repertoire of restriction enzymes useful for various DNA cloning tasks. Here
      we present protocols for the assembly, expression, and purification of cloning
      grade ZFNs and their use for DNA cloning. We focus our discussion on the assembly
      of a dual-cassette plant transformation vector, as an example of a task that is
      nearly impossible to perform using the current collection of naturally occurring
      and recombinant 6-8 bp long restriction enzymes.

PMID- 20680837
TI  - In vitro assessment of zinc finger nuclease activity.
AB  - The technical advances in developing artificial endonucleases, such as zinc
      finger nucleases (ZFNs), have opened a wide field of applications in the genome
      engineering arena, including the therapeutic correction of mutated genes in the
      human genome. Gene editing frequencies of up to 50% in human cells under non
      selective conditions reveal the power of the ZFN technology. Activity and
      toxicity of ZFNs are determined by a number of parameters, including the
      specificity of DNA binding, the kinetics of dimerization of the two ZFN subunits,
      and the catalytic activity. In order to investigate these parameters
      individually, a cell-free system that models these reactions is essential. Here,
      we present a simple and fast method for the functional testing of ZFNs in vitro.

PMID- 20680838
TI  - Quantification of zinc finger nuclease-associated toxicity.
AB  - The recent development of artificial zinc finger nucleases (ZFNs) for targeted
      genome editing has opened a broad range of possibilities in biotechnology and
      gene therapy. The ZFN technology allows a researcher to deliberately choose a
      target site in a complex genome and create appropriate nucleases to insert a DNA
      double-strand break (DSB) at that site. Gene editing frequencies of up to 50% in
      non-selected human cells attest to the power of this technology. Potential side
      effects of applying ZFNs include toxicity due to cleavage at off-target sites.
      This can be brought about by insufficient specificity of DNA binding, hence
      allowing ZFN activity at similar target sequences within the genome, or by
      activation of the ZFN nuclease domains before the nuclease is properly bound to
      the DNA. Here, we describe two different methods to quantify ZFN-associated
      toxicity: the genotoxicity assay is based on quantification of DSB repair foci
      induced by ZFNs whereas the cytotoxicity is based on assessing cell survival
      after application of ZFNs.

PMID- 20680839
TI  - A rapid and general assay for monitoring endogenous gene modification.
AB  - The development of zinc finger nucleases for targeted gene modification can
      benefit from rapid functional assays that directly quantify activity at the
      endogenous target. Here we describe a simple procedure for quantifying mutations
      that result from DNA double-strand break repair via non-homologous end joining.
      The assay is based on the ability of the Surveyor nuclease to selectively cleave
      distorted duplex DNA formed via cross-annealing of mutated and wild-type
      sequence.

PMID- 20680840
TI  - Engineered zinc finger proteins for manipulation of the human mitochondrial
      genome.
AB  - Currently there are no effective methods to manipulate or modify particular
      sequences in mammalian mitochondrial DNA (mtDNA) within cells. The availability
      of such methods would be of great value for basic mitochondrial research and
      would aid in development of therapies for diseases linked with mutations in
      mtDNA. Engineered zinc finger proteins have been used as powerful tools for
      intervening in nuclear gene expression and modifying nuclear DNA in a sequence
      specific manner. Here, basic methods that are helpful in adapting the engineered
      zinc finger technology for targeting the DNA in mitochondria are presented with
      the main emphasis on mitochondrial import of zinc finger proteins.

PMID- 20680841
TI  - High-efficiency gene targeting in Drosophila with zinc finger nucleases.
AB  - We describe a method for making targeted double-strand breaks in Drosophila
      melanogaster using zinc finger nucleases (ZFNs). After design and construction of
      the appropriate coding sequences, synthetic mRNAs for the ZFNs are injected
      directly into fly embryos. Frequencies of target cleavage and mutagenesis in the
      range of 1-10% have been achieved at several different loci. A donor DNA carrying
      desired sequence changes can be incorporated in the injection mix and leads to
      targeted gene replacement, with particularly good efficiency when the recipient
      embryos are defective for nonhomologous end joining.

PMID- 20680842
TI  - Using zinc finger nucleases for efficient and heritable gene disruption in
      zebrafish.
AB  - While the experimental tools developed for zebrafish have continued to advance
      the organism as a laboratory model, techniques for reverse genetics remain
      somewhat limited in scope. Zinc finger nucleases (ZFNs), chimeric fusions between
      DNA-binding zinc finger proteins and the non-specific cleavage domain of the FokI
      endonuclease, hold great promise for targeted mutagenesis in zebrafish, as
      demonstrated by two recent publications (Doyon et al., 2008, Nat Biotechnol. 26,
      702-708; Meng et al., 2008, Nat Biotechnol. 26, 695-701). Because ZFNs can be
      designed to recognize a unique sequence in the genome, they can specifically bind
      and cleave a target locus, creating a double-strand break (DSB) that is repaired
      by one of two major DNA repair pathways. Repair by one of these pathways, non
      homologous end joining, is often mutagenic, allowing one to screen for induced
      mutations in the target locus. By injecting into zebrafish embryos RNA encoding
      ZFNs that target three different loci, two groups have shown that ZFNs work
      efficiently to induce somatic and germline mutations (reviewed in (3)). We review
      here protocols for injection of ZFN-encoding mRNA into zebrafish embryos,
      screening of injected fish for induced mutations, and subsequent recovery of the
      induced mutations.

PMID- 20680843
TI  - A transient assay for monitoring zinc finger nuclease activity at endogenous
      plant gene targets.
AB  - Advances in plant biology have been frustrated by the lack of an efficient means
      to create targeted mutations. Zinc finger nucleases (ZFNs) hold much promise for
      overcoming this limitation: they can be used to generate targeted gene knockouts
      through imprecise repair of broken chromosomes by non-homologous end joining
      (NHEJ), or they can stimulate the introduction of specific DNA sequence changes
      through homologous recombination. Critical to the function of ZFNs is their
      ability to access and cleave chromosomal target sites. Numerous factors may
      obscure cleavage, including packaging of DNA into chromatin, DNA methylation, or
      the presence of other proteins at the target site. Here we describe a transient
      assay that rapidly assesses ZFN function at chromosomal targets in plant cells.
      The assay monitors the ability of a ZFN to introduce mutations by imprecise
      repair through NHEJ, resulting in the loss of a restriction endonuclease
      recognition sequence. The requirement for the restriction endonuclease
      recognition sequence coincident with the ZFN spacer region has thus far not been
      a limiting factor in identifying ZFN target sites in genes of interest suitable
      for this assay.

PMID- 20680844
TI  - Validation and expression of zinc finger nucleases in plant cells.
AB  - Zinc finger nucleases (ZFNs) can be designed to target virtually any long stretch
      of DNA sequence. Their expression in living cells has been shown to lead to gene
      targeting via homologous recombination, site-specific mutagenesis, and targeted
      DNA integration in various species. A variety of assays have been developed to
      test ZFN activity both in vitro and in vivo, and an assortment of vectors have
      been constructed to facilitate the analysis and expression of ZFNs in mammalian,
      and specifically human cells, as well as in other model organisms. Here we
      describe a set of protocols and vectors that were specifically designed to
      analyze ZFN activity in plant cells. Our assays provide the user with versatile
      tools and simple protocols for in-planta analysis of ZFN activity on transiently
      delivered and stably integrated mutated plant reporter (GUS)-encoding genes.
      Specifically designed for maximum compatibility with a generalized plant
      expression system, our vector system also allows easy assembly of ZFN plant
      transformation vectors for gene-targeting experiments in plants.

PMID- 20680845
TI  - Non-FokI-based zinc finger nucleases.
AB  - The design of functional proteins is one of the most challenging areas of protein
      research. We have constructed zinc finger peptides with metal-dependent
      hydrolytic abilities by mutating the zinc ligands in classical zinc fingers,
      without the need to add a FokI or other DNA cleavage domain. The designed
      peptides acquired DNA cleavage ability successfully, retaining the proper zinc
      finger folding and DNA targeting ability. We have also succeeded in site-specific
      DNA cleavage in the presence of cerium ions by introducing a lanthanide ion
      binding loop as a linker of zinc finger motifs.

PMID- 20680846
TI  - Designing and testing chimeric zinc finger transposases.
AB  - Transposons have been effectively utilized as non-viral gene delivery systems
      that are capable of promoting stable transgene expression in mammalian and human
      cells. Two specific transposon systems, Sleeping Beauty (SB) and piggyBac (PB),
      have been successfully modified by the addition of a zinc finger (ZF) DNA-binding
      domain as a strategy for directing transposon integration near ZF target sites in
      a host cell genome. Site-directed integration could improve transposon-mediated
      gene transfer by limiting positional effects on transgene integration, limiting
      genotoxicity, and improving the overall safety in gene therapy applications. In
      this chapter, we describe methodology for creating and characterizing functional
      chimeric ZF transposases and experimental approaches for testing their
      transpositional activity in human cells.

PMID- 20680847
TI  - Seeing genetic and epigenetic information without DNA denaturation using sequence
      enabled reassembly (SEER).
AB  - Virtually all methods for reading the sequence of bases in DNA rely on the
      ability to denature double-stranded DNA into single strands and then use Watson
      Crick base-pairing rules to hybridize the strands with high specificity to
      another DNA primer or probe. However, nature frequently uses an alternative
      method, reading the sequence information directly from double-stranded DNA using
      sequence-specific DNA-binding proteins. Here we describe methods for the
      construction and testing of sequence probes based on engineered zinc finger DNA
      binding proteins. Background is reduced using split-reporter molecules, and
      signal is amplified using enzymatic reporters. The resulting sequence-enabled
      reassembly (SEER) probes can be configured to detect DNA sequence (genetic) or
      DNA methylation (epigenetic) information.

PMID- 20680848
TI  - Zinc finger-mediated live cell imaging in Arabidopsis roots.
AB  - Following the elucidation of recognition codes, artificial zinc finger (ZF)
      domains can now be assembled to create custom-made DNA-binding proteins in which
      the alpha helix of each zinc finger mediates an interaction with 3 or 4 bp of
      DNA. A module of consecutive zinc finger domains, designated a polydactyl zinc
      finger (PZF) domain, is thus capable of binding an extended number of base pairs
      of DNA. Besides the multitude of utilities of PZF domains addressed in other
      chapters, we have shown that they can also be used for live cell imaging of
      repetitive DNA sequences in Arabidopsis, as well as in mouse cells by generating
      and expressing PZF:GFP fusion proteins (1). Here we provide a detailed protocol
      for the construction of such PZF:GFP reporter proteins using our established
      cloning vehicles, together with a protocol for their expression in plants in
      order to achieve in vivo labelling of repetitive DNA. Furthermore we provide an
      accurate quantification method for GFP signals using fluorescent beads
      (FluoSpheres). Single-molecule precision can be obtained using any confocal setup
      once the fluorescent beads have been calibrated against purified GFP. The methods
      can easily be adapted to meet the demands for other situations or for other
      experimental systems.

PMID- 20680849
TI  - Biophysical analysis of the interaction of toxic metal ions and oxidants with the
      zinc finger domain of XPA.
AB  - Zinc-binding domains are frequently present in proteins required for maintaining
      genomic integrity. During recent years there has been accumulating evidence that
      they may be particularly sensitive targets for toxic metal ions, leading, for
      example, to DNA repair inhibition. Here, we present a broad set of methods for
      assessing the impact of metal ions on the zinc-binding domain of xeroderma group
      A protein, an essential factor in nucleotide excision repair. We envisage that
      these methods will be useful also for other proteins.

PMID- 20680850
TI  - Preparation and zinc-binding properties of multi-fingered zinc-sensing domains.
AB  - Cys(2)His(2) zinc finger proteins (ZFPs) adopt a highly conserved betabetaalpha
      fold, which is stabilized by tetrahedral coordination of a central zinc ion by
      two cysteine and two histidine residues. Although the function of most zinc
      fingers is sequence-specific DNA binding, other roles such as zinc sensing have
      been identified. Here, methods are described to produce micromole quantities of
      zinc-sensing zinc finger domains from the Zap1 (two zinc fingers) and MTF-1 (six
      zinc fingers) transcription factors. Procedures are outlined to isolate
      recombinant zinc finger proteins from a bacterial expression system that
      generates both soluble intracellular (Zap1) and insoluble inclusion body (MTF-1)
      forms. Isolated proteins are reduced and subsequently HPLC purified at low pH and
      lyophilized, which generates proteins that are ideal for zinc-binding studies or
      metal substitution studies and stable during long-term storage. NMR and
      calorimetric methods are described to measure relative and individual zinc ion
      affinities in multi-fingered proteins, which is an essential step in unraveling
      the zinc-sensing mechanism of MTF-1 and Zap1.

PMID- 20680851
TI  - Using ChIP-seq technology to identify targets of zinc finger transcription
      factors.
AB  - Half of all human transcription factors are zinc finger proteins and yet very
      little is known concerning the biological role of the majority of these factors.
      In particular, very few genome-wide studies of the in vivo binding of zinc finger
      factors have been performed. Based on in vitro studies and other methods that
      allow selection of high affinity-binding sites in artificial conditions, a zinc
      finger code has been developed that can be used to compose a putative recognition
      motif for a particular zinc finger factor (ZNF). Theoretically, a simple
      bioinformatics analysis could then predict the genomic locations of all the
      binding sites for that ZNF. However, it is unlikely that all of the sequences in
      the human genome having a good match to a predicted motif are in fact occupied in
      vivo (due to negative influences from repressive chromatin, nucleosomal
      positioning, overlap of binding sites with other factors, etc). A powerful method
      to identify in vivo binding sites for transcription factors on a genome-wide
      scale is the chromatin immunoprecipitation (ChIP) assay, followed by
      hybridization of the precipitated DNA to microarrays (ChIP-chip) or by high
      throughput DNA sequencing of the sample (ChIP-seq). Such comprehensive in vivo
      binding studies would not only identify target genes of a particular zinc finger
      factor, but also provide binding motif data that could be used to test the
      validity of the zinc finger code. This chapter describes in detail the steps
      needed to prepare ChIP samples and libraries for high throughput sequencing using
      the Illumina GA2 platform and includes descriptions of quality control steps
      necessary to ensure a successful ChIP-seq experiment.

PMID- 20680852
TI  - Crystallization of zinc finger proteins bound to DNA.
AB  - A method is presented for determining conditions for the cocrystallization of
      zinc finger proteins with DNA. The method describes steps beginning with protein
      expression, through purification, design of DNA for cocrystallization, and the
      conditions to screen for cocrystallization.

PMID- 20680853
TI  - Beyond DNA: zinc finger domains as RNA-binding modules.
AB  - Over the last 25 years, we have learned that many structural classes of zinc
      binding domains (zinc fingers, ZFs) exist and it has become clear that the
      molecular functions of these domains are by no means limited to the sequence
      specific recognition of double-stranded DNA. For example, ZFs can act as protein
      recognition or RNA-binding modules, and some domains can exhibit more than one
      function. In this chapter we describe the progress that has been made in
      understanding the role of ZF domains as RNA-recognition modules, and we speculate
      about both the prevalence of such functions and the prospects for creating
      designer ZFs that target RNA.

PMID- 20680854
TI  - Expanding antiretroviral therapy provision in resource-constrained settings:
      social processes and their policy challenges.

PMID- 20680855
TI  - "It is not an easy decision on HIV, especially in Zambia": opting for silence,
      limited disclosure and implicit understanding to retain a wider identity.
AB  - As universal testing moves onto the HIV agenda, there is a need for more
      understanding of the relatively low uptake of HIV testing and the dynamics of
      disclosure in Sub-Saharan Africa. Despite the expanding provision of anti
      retroviral therapy in Zambia since 2004, disclosure of HIV status - beyond a
      closed network - remains limited. Drawing on 20 years of living and working in a
      high HIV prevalence country, research on HIV-related stigma and existing
      literature on disclosure, this paper explores the reasons that lie behind limited
      disclosure. Unravelling why HIV disclosure remains "a navigation in a moral
      field", the pattern of silence around HIV and the routine and often subtle
      presence of HIV in daily life reveals two key dynamics. The first dynamic is
      shifting public/private boundaries and retaining a wider identity. People living
      with HIV juggle the pragmatic advantages of disclosing to a limited circle with
      the importance of maintaining not only their moral integrity, status and (for
      some) professional and group identity but also of maintaining their privacy. A
      more public disclosure ("speaking it" more widely) shifts private-public
      boundaries and can be threatening, dangerous and can fix identity. Furthermore,
      disclosure carries obligations which, given high levels of poverty, can be hard
      to meet. The second dynamic is a pattern of implicit understanding. It can be
      easier in a context of high HIV prevalence to opt for silence, in its various
      forms, with the presence of HIV implicitly understood but not often explicitly
      spoken about. Although this gives more room for manoeuvre and for respect,
      silence too can be dangerous and certain situations dictate that it is better to
      breach the silence. More aggressive promotion of HIV testing needs to both
      respect and consider how to work within these existing dynamics to facilitate
      safe disclosure.

PMID- 20680856
TI  - "You should be grateful to have medicines": continued dependence, altering stigma
      and the HIV treatment experience in Serbia.
AB  - The expectation that universal HIV treatment access in resource-stretched
      settings will reduce stigma is a powerful aspiration that has been incorporated
      into a global rhetoric of hope around the HIV pandemic. Between 2005 and 2007, we
      undertook qualitative longitudinal research with people living with HIV/AIDS
      (PLHIV) in Serbia. We draw here upon the thematic analysis of prospective
      interview accounts of 20 individuals to analyse PLHIV's perceptions of the
      influence of HIV treatment upon their quality of life. HIV is one of few
      conditions in Serbia where its treatment is fully funded by the state.
      Inconsistent treatment delivery means HIV treatment is experienced as insecure.
      Competitive claims for stretched national resources interplay with a moral
      economy which sees PLHIV as "undeserving" citizens. The guilt and anxiety felt by
      PLHIV intersect with severely curtailed employment opportunities, which weaken
      the anticipated restorative and empowering properties embedded within the promise
      of universal HIV treatment access. Rationed expectations of patient or system
      instigated change mean PLHIV's efforts are orientated towards short-term
      individualised self-care, drawing on bureaucratic technologies to mediate their
      uncertainty. These factors integrate to create a specific cultural and historical
      context for an altered but continuing stigma towards PLHIV in this era of
      treatment. This case study cautions against neglecting the underlying structural
      process of stigmatisation that constrains the capacity of PLHIV to participate in
      anti-stigma and community organising activities, indicating that in this setting
      HIV treatment is insufficient alone to reduce stigma or enable major social and
      economic change in the everyday lives of PLHIV.

PMID- 20680857
TI  - Tracking the rise of the "expert patient" in evolving paradigms of HIV care.
AB  - In the context of rolling out antiretroviral treatment programmes in resource
      constrained settings, "expert patients" are hailed as an important step towards
      greater involvement of people living with HIV (PLHIV) in HIV care, and in
      addressing the human resources crisis. The rise of the "expert patient" in HIV
      care partly echoes the move towards greater patient agency and self-management
      that informs health services delivery in industrialised countries. However, the
      "expert patient" also represents a particular moment in the trajectory of PLHIVs'
      quest for greater access to treatment and health care. In this paper, we examine
      the unique evolution and 'instrumentalisation' of PLHIV in public health in
      relation to shifts in the epidemiology, interventions and socio-political
      response related to HIV since the 1980s. Synthesised broadly as "risk-based",
      "empowerment", "structural" and "activist" approaches, four key paradigms are
      identified that attribute different levels of citizenship for PLHIV, that is the
      motivation, agency and responsibility to act not only on their own interests, but
      also on behalf of collective interests in HIV prevention and care. We
      problematise the concept of the patient-citizen by drawing attention to the
      context-specificity of such notions as patient identity, capacity and rights as
      well as the structural realities of access to treatment, and broader engagement
      with the health system. We conclude by offering some thoughts on the
      applicability of 'expert patient' approaches across a broad range of settings.

PMID- 20680858
TI  - When promoting pills is easier than pushing the ABC: a case study from Kavango,
      Namibia.
AB  - One of the challenges faced by AIDS service organisations seeking to engage with
      traditional leaders and community elders in Kavango, north-east Namibia, has been
      the popular view that the messages of the fight against HIV/AIDS contradict local
      cultural values. However, there are indications that this has been changing.
      Staff and volunteers working with AIDS service organisations reported that
      growing numbers of traditional leaders were becoming involved in HIV/AIDS
      programmes, in particular supporting efforts to promote HIV testing and encourage
      more people to take up antiretroviral therapy (ART), which has been available in
      state hospitals in the region since 2005. This paper explores one of the factors
      that appear to be facilitating this broadening of participation in the fight
      against HIV/AIDS. The case is made that increasing familiarity with and
      confidence in ART has contributed to the emergence of an alternative set of signs
      around HIV/AIDS that is more culturally permissive and is not so conducive to
      social representations of a moral disjuncture between HIV/AIDS programmes and
      Kavango culture. This has created opportunities for traditional leaders and
      elders to more easily resolve the tensions between the recognised need to respond
      to "this disease of today", and whilst still performing their role as guardians
      of local culture. This paper is based on ethnographic research conducted in
      Kavango over a period of 18 months during 2007-2008.

PMID- 20680859
TI  - The experience of "medicine companions" to support adherence to antiretroviral
      therapy: quantitative and qualitative data from a trial population in Uganda.
AB  - Good adherence is critical for antiretroviral therapy (ART) in sub-Saharan
      Africa. We report on the characteristics of medicine companions (MCs) chosen by
      Ugandan patients enrolling on ART, and on how MCs were chosen, and what roles
      they played. Baseline data on MCs of 1453 participants in a randomized controlled
      trial comparing facility and home-based delivery of ART in Jinja, Uganda were
      analyzed. Textual data on experience with MCs were collected through in-depth
      interviews among a subsample of 40 trial participants equally divided by sex and
      trial arm. Significantly more women (71%) than men (29%) were recruited. The
      majority (75%) of women participants were either widowed (51%) or separated or
      divorced (24%), whereas most of the men (66%) were married. Women were most
      likely to choose a child as their MC while men were most likely to choose their
      spouse; 41% of women chose an MC under 21 compared with only 14% of men. Only 31%
      of married women chose their husband, compared with 66% of married men who chose
      their wife. Qualitative interviews suggested MCs proved useful for reminding and
      other supportive tasks in the first three months but were generally less
      essential by six months and beyond. Convenience, reliability, and trust were key
      considerations in choosing an MC. Children provided the only alternative for many
      unmarried women, but even some married women felt children made more reliable MCs
      than husbands. Participants who had disclosed their serostatus usually received
      drug-taking reminders from multiple household members. One participant in the
      qualitative sample with poor family relations delayed starting treatment due to
      unwillingness to identify an MC. MCs were generally welcome and useful in
      supporting early adherence. However, disclosure to an MC should not be a
      condition of obtaining treatment.

PMID- 20680860
TI  - Barriers and outcomes: TB patients co-infected with HIV accessing antiretroviral
      therapy in rural Zambia.
AB  - The vulnerabilities that underlie barriers faced by the rural poor whilst trying
      to access and adhere to "free" antiretroviral treatment (ART) demand more
      attention. This paper highlights barriers that poor rural Zambians co-infected
      with tuberculosis (TB) and HIV and their households faced in accessing ART
      between September 2006 and July 2007, and accounts for patient outcomes by the
      end of TB treatment and (more sporadically) beyond October 2009. The analysis
      draws on findings from wider anthropological fieldwork on the converging impact
      of TB, HIV and food insecurity, focusing for the purpose of this paper on
      ethnographic case-studies of seven newly diagnosed TB patients co-infected with
      HIV and their six households (one household had two TB patients). Economic
      barriers included being pushed into deeper poverty by managing TB, rural
      location, absence of any external assistance, and mustering time and extended
      funds for transport and "special food" during and beyond the end of TB. In the
      case of death, funeral costs were astronomical. Social barriers included
      translocation, broken marriages, a sub-ordinate household position, gender
      relations, denial, TB/HIV stigma and the difficulty of disclosure. Health
      facility barriers involved understaffing, many steps, lengthy procedures and
      inefficiencies (lost blood samples, electricity cuts). By the end of TB
      treatment, outcomes were mixed; two co-infected patients had died, three had
      started ART and two had yet to start ART. The three on ART underwent a striking
      transformation in the short term. By October 2009, two more had died and three
      were doing well. The study advocates nutritional support and other material
      support (especially transport funds) for co-infected TB patients until ART is
      accessed and livelihood regained. More prompt diagnosis of TB and reducing steps
      and increasing the reach of the ART programme in rural areas are also
      recommended.

PMID- 20680861
TI  - Lay health workers and HIV programmes: implications for health systems.
AB  - One of the consequences of massive investment in antiretroviral access and other
      AIDS programmes has been the rapid emergence of large numbers of lay workers in
      the health systems of developing countries. In South Africa, government estimates
      are 65,000, mostly HIV/TB care-related lay workers contribute their labour in the
      public health sector, outnumbering the main front-line primary health care
      providers and professional nurses. The phenomenon has grown organically and
      incrementally, playing a wide variety of care-giving, support and advocacy roles.
      Using South Africa as a case, this paper discusses the different forms,
      traditions and contradictory orientations taken by lay health work and the system
      wide effects of a large lay worker presence. As pressures to regularise and
      formalize the status of lay health workers grow, important questions are raised
      as to their place in health systems, and more broadly what they represent as a
      new intermediary layer between state and citizen. It argues for a research agenda
      that seeks to better characterise types of lay involvement in the health system,
      particularly in an era of antiretroviral therapy, and which takes a wider
      perspective on the meanings of this recent re-emergence of an old concept in
      health systems heavily affected by HIV/AIDS.

PMID- 20680862
TI  - Negotiating multiple barriers: health workers' access to counselling, testing and
      treatment in Malawi.
AB  - Malawi is facing a severe HIV and AIDS epidemic with an estimated 12% of its
      population living with the virus. Health workers are on the front lines of the
      HIV epidemic and they face the risk of HIV infection in both their personal and
      professional lives. This mixed method study aimed to explore the enablers and
      barriers to HIV counselling and testing and antiretroviral therapy by health
      workers in Malawi. After qualitative data were collected through in-depth
      interviews with health workers in the Mchinji and Nsanje districts, a survey
      questionnaire was constructed and administered to 906 health workers in eight
      districts in Malawi. A majority (76%) of health workers surveyed reported having
      undergone HIV testing and counselling, of whom 74% reported repeat testing. A
      striking result of the study is that 22% of health workers reported testing after
      occupational exposure to HIV. The proportions of respondents reporting that they
      tested after experiencing symptoms, or self-testing for HIV were 11% each. The in
      depth interviews and the survey revealed multiple challenges that health workers
      face to accessing HIV testing, counselling and treatment, including fear of a
      positive result, fear of stigma and lack of confidentiality. Additional barriers
      included health workers' personal acquaintance with those conducting testing,
      along with their perception of being "role models" which could exacerbate their
      fears about confidentiality. Given health workers' critical role in HIV delivery
      in Malawi, there is need to develop solutions to help health workers overcome
      these barriers.

PMID- 20680863
TI  - Health systems' responses to the roll-out of antiretroviral therapy (ART) in
      India: a comparison of two HIV high-prevalence settings.
AB  - The government of India launched the free anti-retroviral therapy (ART)
      initiative in 2004 and the programme has since scaled up expansion in a phased
      manner. Programme authorities acknowledge problems in scale-up, yet discussions
      have been restricted to operational constraints, with little consideration for
      how local health system responses to HIV/AIDS influence the delivery of ART. This
      paper draws on the perspectives of key informants and people living with HIV
      (PLHIV) to compare delivery of ART in two ART centres in the States of
      Maharashtra and Andhra Pradesh at two distinct points of time. In 2005, data were
      collected through key informant interviews (KIIs) using interview guides and a
      survey of PLHIV using a semi-structured interview schedule. Differences were
      observed in the functioning and resources of the two centres, indicating
      different levels of preparedness which in turn influenced PLHIV's pathways in
      accessing ART. We examine these differences in the light of programme leadership,
      ownership and the roles of public, private and non-governmental organisation
      actors in HIV care. KIIs conducted during a follow-up visit in 2009 focused on
      changes in ART delivery. Many operational problems had been resolved; however,
      new challenges were emerging as a result of the increased patient load. An
      understanding of how ART programmes evolve within local health systems has
      bearing on future developments of the ART programme and must include a
      consideration of the wider socio-political environment within which HIV
      programmes are embedded.

PMID- 20680864
TI  - The impact of Global Health Initiatives at national and sub-national level - a
      policy analysis of their role in implementation processes of antiretroviral
      treatment (ART) roll-out in Zambia and South Africa.
AB  - Global Health Initiatives (GHIs), such as the President's Emergency Plan For AIDS
      Relief (PEPFAR) and the Global Fund to Fight AIDS, TB and Malaria (the GFATM),
      have emerged as new mechanisms for development assistance in health. By 2008,
      GHIs were providing two-thirds of all external funding for HIV/AIDS globally. In
      Zambia and South Africa over the past five years, PEPFAR and the GFATM have
      provided significant funding for the public sector provision of anti-retroviral
      treatment (ART). GHIs are a feature of a new global health governance. A study of
      their role in implementation helps to explore some of the challenges of this new
      system of governance at national and sub-national level. This paper draws on
      policy analysis research that involved 150 interviews with policy-makers at
      national, provincial and district level in both countries, conducted as part of
      Ph.D. fieldwork between August 2007 and June 2008. Research findings show that
      GHIs impacted on policy-implementation processes at national and sub-national
      level, on aspects of the ART programme and the wider health system. Study results
      highlight GHIs impact both through funding and the mechanisms, and processes by
      which their support is provided. Evidence suggests that while GHIs have
      contributed significantly to enabling the rapid scale-up of ART in both the
      countries, they may also have had a negative impact on coordination, the long
      term sustainability of treatment programmes and equity of treatment access. In
      addition, their programmes may have contributed to disconnect between HIV
      prevention and treatment initiatives. The comparative findings from Zambia and
      South Africa highlight some of the challenges in implementation of GHI programmes
      at country and sub-country level that need to be addressed urgently, to mediate
      against negative consequences for the health systems and policy processes in both
      countries.

PMID- 20680865
TI  - Presence and incidence of food-borne pathogens in Australian chicken litter.
AB  - 1. Litter samples were collected at the end of the production cycle from spread
      litter in a single shed from each of 28 farms distributed across the three
      Eastern seaboard States of Australia. 2. The geometric mean for Salmonella was 44
      Most Probable Number (MPN)/g for the 20 positive samples. Five samples were
      between 100 and 1000 MPN/g and one at 10(5) MPN/g, indicating a range of factors
      are contributing to these varying loads of this organism in litter. 3. The
      geometric mean for Campylobacter was 30 MPN/g for the 10 positive samples, with 7
      of these samples being <100 MPN/g. The low prevalence and incidence of
      Campylobacter were possibly due to the rapid die-off of this organism. 4. E. coli
      values were markedly higher than the two key pathogens (geometric mean 20 x 10(5)
      colony forming units (cfu)/g) with overall values being more or less within the
      same range across all samples in the trial, suggesting a uniform contribution
      pattern of these organisms in litter. 5. Listeria monocytogenes was absent in all
      samples and this organism appears not to be an issue in litter. 6. The dominant
      (70% of the isolates) Salmonella serovar was S. Sofia (a common serovar isolated
      from chickens in Australia) and was isolated across all regions. Other major
      serovars were S. Virchow and S. Chester (at 10%) and S. Bovismorbificans and S.
      Infantis (at 8%) with these serovars demonstrating a spatial distribution across
      the major regions tested. 7. There is potential to re-use litter in the
      environment depending on end use and the support of relevant application
      practices and guidelines.

PMID- 20680866
TI  - Effect of environment on Pekin duck behaviour and its correlation with body
      condition on commercial farms in the UK.
AB  - 1. Forty-six flocks of commercially-reared Pekin ducks were studied to determine
      the effects of housing system and environment on the behaviour of farmed ducks
      and its correlation with physical condition. Houses differed predominantly in
      their ventilation, drinking, feeding and brooding systems, and were indicative of
      systems currently in use in the UK. 2. At 41 d of age ducks spent 15% of the time
      feeding, 67% drinking, 42% rooting and 155% dry preening. They spent large
      amounts of time relatively inactive, 435%, or performing comfort behaviours, 17%.
      On average 46% of their time was spent walking and only 18% wet preening. 3. A
      greater proportion of the maximum number of ducks able to use the drinker at any
      one time used the trough; nipple use was least and Plasson use intermediate. The
      proportion of ducks wet preening was not affected by drinker type but increased
      with increasing drinker space (mm/bird). 4. Duck behaviour was little affected by
      commercial production system and was influenced more by environment, age and
      physical condition. Activity at an older age incorporated more of the behaviours
      associated with thermal comfort (panting) and maintenance of plumage condition
      (dry and wet preening). These behaviours increased with increasing temperature,
      relative humidity and atmospheric ammonia. Poor walking ability was correlated to
      increased frequency of panting, reduced activity at the drinker, and longer
      resting bouts.

PMID- 20680867
TI  - Characteristics of ammonia and carbon dioxide releases from layer hen manure.
AB  - 1. Ammonia (NH(3)) is an important gaseous pollutant generated from manure in
      commercial poultry farms and has been an environmental, ecological, and health
      concern. Poultry manure also releases carbon dioxide (CO(2)), which is a
      greenhouse gas and is often used as a tracer gas to calculate building
      ventilation. 2. A 38-d laboratory study was conducted to evaluate the
      characteristics of NH(3) and CO(2) releases from layer hen manure using 4 manure
      reactors (122 cm tall, 38 cm internal diameter), which were initially filled with
      66 cm deep manure followed by weekly additions of 5 cm to simulate manure
      accumulation in commercial layer houses. 3. The average daily mean (ADM) NH(3)
      and CO(2) release fluxes for the 4 reactors during the entire study were 1615 +/-
      211 microg/s.m(2) (ADM +/- 95% confidence interval) and 100 +/- 03 mg/s.m(2),
      respectively. The daily mean NH(3) and CO(2) releases in individual reactors
      varied from 352 to 6791 microg/s.m(2) and from 66 to 205 mg/s.m(2), respectively.
      4. The ADM NH(3) release flux was within the range of those obtained in 4 high
      rise layer houses by Liang et al. (2005, Transactions of the ASAE, 48). However,
      the CO(2) release flux in this study was about 10 to 13 times as high as the data
      reported by Liang et al. (2005). Fresh manure had greater NH(3) release potential
      than the manure in the reactors under continuous ventilation. Manure with higher
      contents of moisture, total nitrogen, and ammonium in the 4th weekly addition
      induced 11 times higher NH(3) and 75% higher CO(2) releases immediately after
      manure addition compared with pre-addition releases.

PMID- 20680868
TI  - Interaction between ascites susceptibility and CO during the second half of
      incubation of two broiler lines. Effect on embryonic development and hatching
      process.
AB  - 1. Because CO(2) during the second half of incubation is known to influence air
      cell and blood gases, and embryo development, it is postulated that post-hatch
      development and ascites sensitivity could also be influenced. 2. An ascites
      susceptible (A) and an ascites resistant (E) broiler line were incubated under
      standard incubation or high CO(2) conditions (up to 4%) from embryonic day (ED)
      10 onwards. The embryonic development and the hatching process of these two lines
      were compared when incubated under standard or high CO(2) conditions from over
      the second half of incubation. 3. The A line, selected for high post-hatch growth
      rate, exhibited a higher relative embryo weight from ED10 until ED16, which was
      supported by a higher air cell pCO(2), lower air cell pO(2), higher
      corticosterone and thyroid hormones and earlier hatching time. 4. Incubation
      under high CO(2) increased air cell pCO(2), retarded yolk consumption, and
      decreased glycogen concentration in the liver at hatch. Hatchability decreased in
      both lines when incubated under high CO(2), due to an increased late mortality of
      embryos that died before IP. 5. These results suggest that the development and
      metabolism of CO(2)-incubated embryos differ from control incubated embryos.

PMID- 20680869
TI  - Effect of sex and genotype on carcase composition and nutritional characteristics
      of chicken meat.
AB  - 1. The aim of this study was to examine the effect of sex and genotype on carcase
      composition and nutritional and sensory characteristics of chicken meat. The
      "Geline de Touraine" (GT) characterised by high carcase fatness was compared with
      an experimental crossbreed (EC) and "Label rouge" (LR) genotype. 2. Females
      compared with males, and GT chickens compared with LR and EC chickens were
      characterised by increased carcase fatness and an increased lipid level in thigh
      meat. 3. In both breast and thigh meat, the percentage of monounsaturated fatty
      acids was increased and the percentage of polyunsaturated fatty acids was
      decreased. However, these effects did not affect sensory characteristics of meat
      particularly those of roasted breast fillets containing very low lipid level by
      comparison with thigh meat. 4. Finally, in our study, high carcase fatness was
      related to high intermuscular fatness affecting the nutritional characteristics
      of meat but not its sensory attributes.

PMID- 20680870
TI  - Effects of dietary chromium chloride, nicotinic acid and copper sulphate on meat
      of broilers.
AB  - 1. Combinations of chromium and copper were added to the diet to assess their
      effects on broiler meat characteristics. 2. For this purpose 175 one-day-old
      broiler chicks were divided into 7 equal groups and were given treatment feeds
      containing copper sulphate, chromium chloride and nicotinic acid in different
      combinations. 3. The study was carried out for 5 weeks and samples were collected
      at the end of 15, 29 and 35 d of treatment and at 42 d after a withdrawal period
      of one week. 4. Cholesterol content had decreased significantly in breast meat at
      d 29 in all treatment groups. In thigh meat, it decreased significantly at d 29
      in groups receiving two concentrations of chromium + two concentrations of
      copper. Cholesterol content remained lower even after withholding the treatment
      for one week. 5. Crude fat content decreased significantly in breast meat in all
      treatment groups. In thigh meat, at d 29, a significant reduction in crude fat
      was observed only in birds receiving low chromium and high copper. 6. Crude
      protein at d 29 increased significantly in breast meat of birds receiving low
      chromium and high copper, and low or high chromium, while it decreased
      significantly in treatment groups after withholding the treatment. In thigh meat,
      at d 29, it increased significantly in treatment groups but decreased
      significantly after withholding the treatment. 7. It was concluded that chromium
      and copper, along with nicotinic acid, have modulating effects on broiler meat
      under tropical conditions.

PMID- 20680871
TI  - Single-tube real-time multiple allele-specific PCR for genotyping chicken Mx gene
      G2032A SNP.
AB  - 1. A non-synonymous, single nucleotide polymorphism (G to A) at position 2032
      (Ser 631 Asn) of the chicken Mx gene has been demonstrated to be related to
      resistance to antiviral activity. This study developed a new real-time PCR-based
      allelic discrimination assay for the rapid genotyping of the chicken Mx gene
      G2032A SNP. The distribution of the Mx gene G2032A SNP genotypes and the allele
      frequencies of A and G alleles among different chicken breed populations were
      screened with the use of this method. 2. We combined previously described allele
      specific PCR and SYBR Green I-based real-time PCR melting curve analysis with a
      novel primer design strategy. A pair of outer nested primers was designed to
      amplify a fragment containing the SNP site, and two 3'-specific, allele-specific
      primers were combined with the outer primers to amplify SNP-specific fragments.
      Genotypes were identified based on the characteristic melting temperature of the
      SNP-specific fragments. 3. Genotyping assignments were successfully performed on
      samples from 8 chicken breeds, which were analysed by agarose gel electrophoresis
      of the PCR products and compared with results obtained from the direct sequencing
      of the outer primer amplicon. Five native breeds from Southern China carried a
      relatively higher frequency of the resistant A allele than the three commercial
      chicken lines. 4. This single-tube real-time multiplex allele-specific PCR assay
      is rapid, reliable, sensitive and easy to perform. It is appropriate for high
      throughput sample analysis in large population-based Mx SNP genotyping studies.

PMID- 20680872
TI  - Characterisation and response of intestinal microflora and mucins to manno
      oligosaccharide and antibiotic supplementation in broiler chickens.
AB  - 1. An experiment was conducted to characterise and evaluate, in comparison to
      zinc bacitracin (ZnB), the response of intestinal microflora and mucins to manno
      oligosacchares (MOS, Bio-MOS(R), Alltech Biotechnology, Nicholasville, Kentucky,
      USA). 2. Supplementation of MOS and ZnB selectively increased the intensity of
      sulphomucins. As revealed by the plate culture method, MOS accelerated the
      maturation of gut microflora by promoting the growth of lactobacilli in the ileal
      mucosa and vice versa on ileal and caecal clostridia. Unlike MOS, ZnB suppressed
      the growth of intestinal bacteria, especially those of lactobacilli and
      clostridia. Use of T-RFLP further revealed that MOS increased the diversity of
      lactobacilli in the ileum and ileal mucosa but the opposite was observed for ZnB.
      It also appears that MOS and ZnB possessed a common property in differentially
      favouring the growth of certain Lactobacillus species. There was also evidence to
      show that both MOS and ZnB also increased the homogeneity of the gut microflora,
      possibly through the regulation of the overall gut bacterial communities. 3.
      Improvement in intestinal microbial homogeneity and mucin synthesis, coupled with
      the differential selections for certain specific beneficial bacterial species,
      may ultimately be proven to be the target mechanisms in the search for more
      effective alternatives to antibiotics.

PMID- 20680873
TI  - The effect of feeding essential oils on broiler performance and gut microbiota.
AB  - 1. In this study the effect of a blend of essential oils (EO) comprising 15
      g/tonne thymol and 5 g/tonne cinnamaldehyde on the performance and intestinal
      microbiota of broilers was investigated. 2. A total of 720 male Ross broilers
      were divided into two dietary treatments with 12 replicate pens per treatment.
      Broilers were given a control soybean-wheat-based diet with or without added EO
      in two diet phases (0-21 d and 22-42 d). 3. The blend of EO increased body weight
      gain of broilers from 0 to 42 d by 45%. 4. Caecal microbiota were affected by the
      EO blend; in particular increases in the proportions of Lactobacillus and
      Escherichia coli at 41 d was observed. 5. The EO blend had major effects on
      caecal metabolites. The proportion of caecal butyrate at 20 and 41 d of age
      increased, whereas the proportion of caecal acetic acid at 20 d, and propionic
      acid and isovaleric acid at 41 d, decreased with the EO blend. In addition, the
      caecal proportion of spermine increased and tyramine decreased at 41 d of age
      with the EO treatment. 6. The present study shows that EO supplementation exerts
      a positive effect on intestinal microbiota with a concomitant enhancement in
      growth performance. The study suggests that modulation of broiler gut microbiota
      composition and activity through the administration of EO offers an effective
      means for improving broiler performance.

PMID- 20680874
TI  - Effects of inulin on growth performance, nutrient digestibility and metabolisable
      energy in broiler chickens.
AB  - 1. A 35 d feeding trial with 480 d-old male broiler chickens (Cobb) was conducted
      to evaluate the effects of graded levels of inulin (0, 5, 10, 15 and 20 g/kg
      diet) in a maize-soybean meal based diet on growth performance, AME(N) and
      apparent ileal digestibility (AID) of crude protein, amino acids, starch, crude
      fat and fatty acids. A commercial product (Inulina 95) containing 9140 g/kg of
      inulin and a degree of polymerisation (DP) ranging from DP 1-10 to DP 51-60 was
      used. 2. The performance of birds (feed intake, BW gain and feed to gain ratio)
      was not affected by the different dietary inclusions of inulin. 3. Dietary inulin
      significantly improved the AID coefficient of crude protein and crude fat. Also,
      there was a significant effect of inulin on the digestibility of most amino acids
      (10 out of 15) and major fatty acids (oleic and linoleic acids). The AID
      coefficient of starch and the AME(N) content of diets were not affected by inulin
      inclusion. 4. In conclusion, the current study showed that inulin supplementation
      improved the digestibility of protein and fat in a maize-soybean meal based diet,
      but had no effect on the performance of broiler chickens.

PMID- 20680875
TI  - Effects of different yeast cell wall supplements added to maize- or wheat-based
      diets for broiler chickens.
AB  - 1. Three experiments were carried out to study the effects of two experimental
      yeast cell wall (YCW) supplements, one from the yeast extract industry and the
      other from the brewery industry, added to maize or wheat based-diets, on
      performance and intestinal parameters of broiler chickens (Ross 308). 2. In the
      first and second experiments, a completely randomised block design with 4
      experimental treatments was used: T-1) Negative control, no additives T-2)
      Positive control, avilamycin group (10 mg/kg feed), T-3) Yeast extract-YCW (500
      mg/kg), and T-4) Brewery-YCW (500 mg/kg feed). There were 6 replicates of 20
      (experiment 1) and 22 (experiment 2) chicks per treatment. 3. In experiment 1
      (wheat based diets), yeast extract-YCW increased BW and daily feed intake (42 d).
      The effects were comparable to those of avilamycin. In experiment 2 (maize based
      diet), avilamycin, yeast extract-YCW and brewery-YCW treatments improved the feed
      conversion ratio with respect to the negative control group (0 to 14 d). 4. At 24
      d, in both experiments, the ileal nutrient digestibility and ileal bacterial
      counts were not affected by any experimental treatment. In maize diets, lower
      intestinal viscosity was obtained with avilamycin, yeast extract-YCW and brewery
      YCW than with the negative control. In wheat diets, yeast extract-YCW and brewery
      YCW reduced intestinal viscosity. 5. A third experiment was conducted to study
      the effect of yeast extract-YCW on animal performance, intestinal mucosa
      morphology and intestinal viscosity. A 2 x 2 factorial arrangement of treatments
      was used; one factor was the dietary yeast extract-YCW supplementation (0 or 500
      mg/kg feed) and the other the cereal in the diet (maize or wheat). 6. At 43 d,
      the heaviest BW was in chickens fed on yeast extract-YCW compared to those given
      the negative control. At 22 d, yeast extract-YCW increased villus height, mucus
      thickness and number of goblet cells with respect to negative control. 7. Results
      of these experiments suggest that supplementation of yeast extract-YCW to broiler
      chicken diets increased animal performance by favouring intestinal mucosal
      development.

PMID- 20680876
TI  - Effects of karaya saponin and Rhodobacter capsulatus on yolk cholesterol in
      laying hens.
AB  - 1. It has been reported that karaya saponin and Rhodobacter capsulatus
      individually have hypocholesterolaemic activity in laying hens. This study
      focuses on the effect of adding karaya saponin with R. capsulatus to hen's diet
      with regard to serum and egg yolk cholesterol and triglycerides. 2. A total of 56
      Boris Brown laying hens were divided into 7 groups at 20 weeks of age.
      Combinations of 25, 50, 75 mg kg(-1) karaya saponin and R. capsulatus 200 and 400
      mg kg(-1) were used as treatment groups. 3. After 8 weeks of supplementation, the
      effects of all the combinations of karaya saponin and R. capsulatus on serum and
      egg yolk cholesterol, triglycerides, and high-density lipoprotein (HDL)
      cholesterol were greater than either karaya saponin or R. capsulatus alone. The
      combination of karaya saponin 50 mg kg(-1)+ R. capsulatus 400 mg kg(-1) exhibited
      the greatest reduction of serum (325%) and yolk (225%) cholesterol and the
      greatest increase of faecal, liver bile acids and yolk fatty acid (oleic,
      linoleic and linolenic) concentrations. In addition, egg production and yolk
      colour were significantly improved by the combined use of karaya saponin and R.
      capsulatus supplementation. 4. Therefore, the dietary supplementation of karaya
      saponin and R. capsulatus may lead to the production of a low-cholesterol egg,
      with production performance maintained at a standard level.

PMID- 20680877
TI  - Effects of structure and xylanase treatment of brewers' spent grain on
      performance and nutrient availability in broiler chickens.
AB  - 1. A factorial (2 x 3) feeding trial was set up to investigate the effects of
      coarse or finely ground brewers' spent grain (BSG) and xylanase treatment, either
      with no xylanase, top-dressed with xylanase or pre-treated with xylanase. 2. The
      experimental diets shared the same basal formulation and were fed to male broiler
      chickens (Ross 308) housed in individual cages from 12 to 29 d of age. 3.
      Xylanase pre-treatment reduced the dietary concentration of arabinoxylan by 15
      30%. Pellet durability increased when BSG was ground. 4. Feed utilisation was
      significantly higher (6%) when the birds were given coarse BSG rather than ground
      BSG, whereas there was no significant effect of enzyme treatment. Apparent
      metabolisable energy was unaffected by the dietary treatments. 5. The overall
      starch digestibility was high (99%), with no dietary differences, whereas ileal
      protein digestibility was low (57%). Xylanase top-dressing tended to improve
      ileal protein digestibility but, in general, xylanase treatment had no major
      effect on overall performance in male broilers given diets with BSG.

PMID- 20680878
TI  - Effect of soybean meal substitution by different concentrations of sunflower meal
      on egg quality traits of white and coloured dwarf dam lines.
AB  - 1. The effect of soybean meal substitution by different concentrations of
      sunflower meal on egg quality traits of white and coloured dwarf dam lines was
      investigated. 2. A total of 144 dwarf hens (38 weeks of age) from the same hatch
      were randomly divided into 12 groups of 12 birds (4 dietary treatments x 3
      replicates). 3. A 2 x 4 factorial design was used to study the effect of 2 lines
      (Factor A) and substitution of soybean meal (SBM) with 4 concentrations (0, 10,
      15 and 20%) of sunflower meal (SFM) [Factor B] on egg quality traits of dwarf dam
      line hens. 4. All the diets were designed to be isocaloric (113 MJ ME/kg) and
      isonitrogenous (180 g/kg crude protein) The duration of the experiment was 12
      weeks. 5. Analysis of variance indicated a highly significant line effect. There
      were non-significant effects of substitution of soybean meal with different
      concentrations of sunflower meal on egg quality traits except for Haugh unit. 6.
      White plumaged dwarf broiler breeder dam line produced significantly fewer, but
      larger, eggs than coloured dwarf dam line hens.

PMID- 20680879
TI  - Broiler responses to supplementation of phytase and admixture of carbohydrases
      and protease in maize-soyabean meal diets with or without maize Distillers' Dried
      Grain with Solubles.
AB  - 1. This experiment investigated growth performance and nutrient utilisation
      responses of broilers to partial replacement of maize and soyabean meal in
      broiler diets with 100 g kg(-1) maize Distillers' Dried Grain with Solubles
      (mDDGS) as well as responses to supplementation of an admixture of carbohydrases
      and protease (XAP) or phytase individually or in combination in the diets. 2. A
      total of 288 one-day-old broilers were allocated to 8 treatments in a randomised
      complete block design and a 2 x 2 x 2 factorial arrangement of treatments. The
      three factors were two levels each of mDDGS (0 or 100 g kg(-1)), phytase (0 or
      1000 FTU kg(-1)), and XAP (0 or 500 mg kg(-1)). 3. Each treatment had 6 replicate
      cages with 6 birds per replicate cage. The control diets were formulated to meet
      all nutrient requirements of broilers according to National Research Council
      recommendations of 1994, but were marginally deficient in non-phytate P and ME.
      4. Weight gain and gain:food were higher in broilers receiving diets containing
      mDDGS. The coefficient of apparent ileal N digestibility was lower in diets with
      mDDGS. Phytase increased the coefficient of apparent ileal DM digestibility in
      all diets. 5. Phytase improved the coefficient of the apparent total tract DM
      retention independently of mDDGS and tended to improve the coefficient of
      apparent P retention in the diets without mDDGS. The enzymes were additive in
      their effects in the diets with mDDGS. Overall, the results showed that adding
      100 g kg(-1) mDDGS to a maize-soyabean meal diet had no negative effect on growth
      when energy and nutrient concentrations were similar to the maize-soyabean meal
      diet, and that phytase or an admixture of carbohydrases and protease individually
      or in combination modestly improved nutrient utilisation independently of mDDGS
      addition. Combination of the enzymes did not produce greater benefit than the use
      of phytase alone.

PMID- 20680880
TI  - Brooding temperatures for chicks acclimated to heat during incubation: effects on
      post-hatch intestinal development and body weight under heat stress.
AB  - 1. The objective was to evaluate the effects of brooding temperature on
      intestinal development, oxidative organ damage, and performance of chicks
      acclimated to high temperature during incubation. The effects of acclimation and
      brooding temperatures on slaughter weights of broilers under heat stress were
      also investigated. 2. Eggs were incubated at either 378 degrees C (INC(Cont)) or
      heat-acclimated at 395 degrees C for 6 h daily from d 10 to d 18 of incubation
      (INC(H)). Brooding temperatures at floor level were set at 32, 335 and 35 degrees
      C (Bt(32), Bt(335), Bt(35), respectively) for the first 5 d. The temperature was
      reduced gradually to 30 degrees C from d 6 to d 10. From 21 to 42 d, broilers
      from INC(Cont) Bt(32) and INC(H) Bt(32) and Bt(35) were divided into two groups;
      half from each group was exposed to daily cyclic higher ambient temperatures,
      while the other half was reared at control temperature. 3. INC(H) chicks had
      lower jejunum, but greater liver and residual yolk sac weights than INC(Cont)
      chicks on the day of hatching. Although INC(H) chicks from Bt(335) and Bt(35) had
      lighter body weights than Bt(32) on d 5, no significant differences were observed
      in the body weight of broilers among treatments at 10 and 21 d. 4. Similar
      jejunum protein, alkaline phosphatase, maltase, glutathione, and malondialdehyde
      contents of chicks from INC(Cont) and INC(H) suggested that heat acclimation
      during incubation has no effect on jejunum enzyme activity or oxidative status of
      chicks. 5. Taking into account INC(H) Bt(35) chicks having lower T(3) levels on d
      5, lower heterophil/lymphocyte (H/L) ratios and similar weights at 42 d under
      heat stress compared with control broilers, the results suggested that although
      higher brooding temperatures had no effect on body weights of INC(H) chicks
      during the brooding period, those broilers may able to cope better with heat
      stress.

PMID- 20680881
TI  - Plasma corticosterone responses to handling in Japanese quail selected for low or
      high plasma corticosterone responses to brief restraint.
AB  - 1. Plasma corticosterone responses to handling in Japanese quail selected for low
      or high corticosterone responses to brief mechanical restraint (low and high
      stress lines) were measured in this study. 2. Initial corticosterone
      concentrations did not differ between the two lines. Corticosterone
      concentrations increased 15 min after handling began in quail handled for 5 or 15
      min, with greater increases in quail from the high stress than the low stress
      line. Integrated corticosterone responses were higher in high stress than low
      stress quail, although the difference between the lines was not significant in
      quail handled for 5 min. 3. Patterns of plasma corticosterone after 15 min
      differed between quail handled for 5 or 15 min. Corticosterone increased further
      or did not change from 15 to 30 min then decreased from 30 to 60 min in quail
      handled for 5 min, whereas corticosterone decreased from 15 to 30 min then did
      not change in quail handled for 15 min. Corticosterone concentrations at 60 min
      remained elevated above initial concentrations, and were similar in quail handled
      for 5 or 15 min. Corticosterone concentrations at 15 min were more than twice as
      high in quail handled for 15 min compared with quail handled for 5 min. 4.
      Although the lines of quail have been selected on the magnitude of corticosterone
      responses, there was still marked variation in responses between birds within
      each line. Some quail in the high stress line showed little or no corticosterone
      response to handling, whilst large responses were seen in some birds of the low
      stress line. The lines of quail differ in characteristics other than
      corticosterone responses, including fear behaviour and reproductive development,
      so the lines provide valuable opportunities to investigate the potential
      significance of differences between individual birds in their corticosterone
      responses.

PMID- 20680883
TI  - Brain and cognitive reserve: mediator(s) and construct validity, a critique.
AB  - The concept of "reserve" has traditionally been defined on the basis of a single
      indicator (e.g., education or intracranial volume) that purports to moderate or
      buffer the effects of brain damage on different clinical outcomes. While studies
      have shown modest effects for some indicators, it has left the concept of
      "reserve" wanting as an explanatory construct. More recently efforts have been
      made to identify groups of indicators hypothesized to represent a construct for
      brain or cognitive reserve. These efforts have also proved wanting because of the
      lack of evidence to justify such a priori groupings of variables into a brain or
      cognitive reserve construct. This theoretical paper addresses the issue of
      construct validity (convergent and discriminant) for both brain and cognitive
      reserve as single or multiple reserve factors. Conceptual models are proposed
      that are (a) derived from the current extant reserve literature and (b)
      empirically testable in order to facilitate establishment of construct validity
      for the commonly used, and perhaps misused, brain and cognitive reserve concepts.

PMID- 20680882
TI  - Agreement between parents and children on ratings of post-concussive symptoms
      following mild traumatic brain injury.
AB  - The level of parent-child agreement on post-concussive symptoms (PCS) was
      examined in children following mild traumatic brain injuries (TBI). As part of a
      larger longitudinal study, 186 children with mild TBI and 99 with orthopedic
      injuries (OI), from 8 to 15 years of age, were recruited prospectively. Parents
      and children completed the PCS Interview (PCS-I) and the Health and Behavior
      Inventory (HBI) at 2 weeks, 1 month, 3 months, and 12 months postinjury. Item
      level correlations between child and parent ratings on both measures of PCS were
      significant but modest in both groups. Parent-child correlations for composite
      scales on the HBI and the total score on the PCS-I were significant in both
      groups, but somewhat higher in the OI group than in the mild TBI group. Mean
      symptom ratings tended to be significantly higher for children as compared to
      parents, especially for somatic symptoms. Parents and children display modest
      agreement when reporting PCS; their ratings correlate significantly, but children
      report higher mean levels of symptoms than parents.

PMID- 20680884
TI  - Improving digit span assessment of short-term verbal memory.
AB  - We measured digit span (DS) in two experiments that used computerized
      presentation of randomized auditory digits with performance-adapted list length
      adjustment. A new mean span (MS) metric of DS was developed that showed reduced
      variance, improved test-retest reliability, and higher correlations with the
      results of other neuropsychological test results when compared to traditional DS
      measures. The MS metric also enhanced the sensitivity of forward versus backward
      span comparisons, enabled the development of normative performance criteria with
      subdigit precision, and elucidated changes in DS performance with age and
      education level. Computerized stimulus delivery and improved scoring metrics
      significantly enhance the precision of DS assessments of short-term verbal
      memory. 

PMID- 20680886
TI  - Temporal distinctiveness and repetition benefits in task switching: disentangling
      stimulus-related and response-related contributions.
AB  - In cued task switching, decreasing switch costs with increasing response-to-cue
      interval (RCI) is a typical finding. The traditional account assumes an
      underlying process of task-set decay. In contrast, we suggest that these RCI
      effects are due to the influence of temporal distinctiveness on cue-based task
      retrieval (or reactivation). The present study explored the task-set components
      that are affected by temporal distinctiveness. According to the idea that a task
      set consists of response-related components and stimulus-related components, we
      manipulated response valence (bivalent vs. univalent) in Experiment 1. The
      results showed that lengthening the RCI leads to a loss of a task-repetition
      benefit, mainly when the RCI changed from the previous trial to the current
      trial, but this data pattern did not depend on response valence. In Experiment 2,
      stimulus valence was manipulated. The results revealed substantially stronger RCI
      effects with bivalent stimuli than with univalent stimuli. Taken together, the
      data are inconsistent with task-set decay accounts and suggest that the influence
      of RCI in task switching modulates cue-based retrieval of stimulus-related task
      components, such as biasing parameters.

PMID- 20680885
TI  - Dyadic concordance among prostate cancer patients and their partners and health
      related quality of life: does it matter?
AB  - Serious and chronic illnesses occur within a family context, affecting not only
      the patient but also the spouse/partner, children and extended family network.
      Spouses/partners are likely to experience the greatest personal impact, and may
      influence patient adjustment. Also, the intimate relationship may be affected by
      the illness experience. This study examined whether dyadic concordance on the
      characteristics of prostate cancer (PC) was related to health-related quality of
      life (HRQOL), psychological distress and marital adjustment in PC patients and
      their female partners. Couples (N=164) completed questionnaires on the appraisals
      of PC, and individual and dyadic adjustment. Patient and partner PC appraisal
      ratings were positively correlated. There was a general pattern of patients and
      partners in concordant dyads, versus those in dyads in which spouses maximised or
      minimised PC characteristics, reporting significantly better individual HRQOL
      outcomes, although there were several exceptions. Patient-partner appraisal
      (dis)agreement generally did not significantly predict dyadic adjustment.
      Overall, results suggest that dyadic disagreement is associated with worse HRQOL
      in couples facing PC.

PMID- 20680887
TI  - Development of a vocabulary of object shapes in a child with a very-early
      acquired visual agnosia: a unique case.
AB  - We report a longitudinal study of an exceptional child (S.R.) whose early
      acquired visual agnosia, following encephalitis at 8 weeks of age, did not
      prevent her from learning to construct an increasing vocabulary of visual object
      forms (drawn from different categories), albeit slowly. S.R. had problems
      perceiving subtle differences in shape; she was unable to segment local letters
      within global displays; and she would bring complex scenes close to her eyes: a
      symptom suggestive of an attempt to reduce visual crowding. Investigations
      revealed a robust ability to use the gestalt grouping factors of proximity and
      collinearity to detect fragmented forms in noisy backgrounds, compared with a
      very weak ability to segment fragmented forms on the basis of contrasts of shape.
      When contrasts in spatial grouping and shape were pitted against each other,
      shape made little contribution, consistent with problems in perceiving complex
      scenes, but when shape contrast was varied, and spatial grouping was held
      constant, S.R. showed the same hierarchy of difficulty as the controls, although
      her responses were slowed. This is the first report of a child's visual
      perceptual development following very early neurological impairments to the
      visual cortex. Her ability to learn to perceive visual shape following damage at
      a rudimentary stage of perceptual development contrasts starkly with the loss of
      such ability in childhood cases of acquired visual agnosia that follow damage to
      the established perceptual system. Clearly, there is a critical period during
      which neurological damage to the highly active, early developing visual
      perceptual system does not prevent but only impairs further learning.

PMID- 20680888
TI  - From left to right: processing acronyms referring to names of political parties
      activates spatial associations.
AB  - In line with previous studies, showing that abstract concepts like "power" or
      "god" implicitly activate spatial associations, in the present study we
      hypothesized that spatial associations are coactivated during the processing of
      acronyms referring to names of political parties as well. In four studies, it was
      found that the reading of these acronyms was accompanied by the implicit
      activation of spatial left-right associations. That is, participants responded
      faster to left-wing parties by means of a left-hand button press and vice versa
      for right-wing parties (Experiments 1 to 3), and participants responded faster
      when a political acronym was presented at the side of the screen corresponding to
      the political orientation of the acronym (Experiment 4). Interestingly, a
      correlation was observed between the effect size for left-wing parties and
      participants' political preferences, suggesting that the reaction time effects
      reflect the perceived distance of a party to one's own political orientation.
      Together these findings indicate that spatial representations activated in
      response to political acronyms do not simply reflect lexical-semantic
      associations or spatial metaphors, but representations of parties' political
      orientation relative to one's own sociopolitical position.

PMID- 20680890
TI  - An extended study of the nonindependence of stimulus properties in human
      classification learning.
AB  - Categorization researchers have tried to verify their models through laboratory
      experiments with simplified stimulus sets, a requirement that can rarely be met
      in real-world situations in which properties are often connected. Still, the
      targeted simplification of the material might be illusory. We replicate and
      extend Love and Markman's (2003) study of the nonindependence of canonical
      stimulus properties such as size, colour, and shape in human classification
      learning, in which the authors concluded that shape takes precedence over other
      dimensions. To support their hypothesis, Love and Markman showed that certain
      classifications are more difficult for participants when shape is combined to one
      of its putative subordinate features, size or colour, than when shape is
      irrelevant to the task. A data set of 290 + 50 adult participants completing one
      or more classification tasks was collected. The results confirm that certain
      combinations of shape, size, and colour can hinder or facilitate classification
      learning, but not necessarily in the form expected by the nonindependence
      postulated by Love and Markman, especially in Experiment 2 where a totally
      reverse pattern of difficulty is observed (shape does not take precedence over
      other dimensions). Also, we show that simple similarity effects in clustering
      retain considerable intuitive appeal and can offer an alternative account to the
      nonindependence of stimulus properties, especially because slight variations in
      the dimensions chosen make the observations of Love and Markman unstable.

PMID- 20680889
TI  - Attentional control constrains visual short-term memory: insights from
      developmental and individual differences.
AB  - The mechanisms by which attentional control biases mnemonic representations have
      attracted much interest but remain poorly understood. As attention and memory
      develop gradually over childhood and variably across individuals, assessing how
      participants of different ages and ability attend to mnemonic contents can
      elucidate their interplay. In Experiment 1, 7-year-olds, 10-year-olds, and adults
      were asked to report whether a probe item had been part of a previously presented
      four-item array. The initial array could either be uncued, be preceded
      ("precued"), or followed ("retrocued") by a spatial cue orienting attention to
      one of the potential item locations. Performance across groups was significantly
      improved by both cue types, and individual differences in children's
      retrospective attentional control predicted their visual short-term and working
      memory span, whereas their basic ability to remember in the absence of cues did
      not. Experiment 2 imposed a variable delay between the array and the subsequent
      orienting cue. Cueing benefits were greater in adults than in 10-year-olds, but
      they persisted even when cues followed the array by nearly 3 seconds, suggesting
      that orienting operated on durable short-term representations for both age
      groups. The findings indicate that there are substantial developmental and
      individual differences in the ability to control attention to memory and that in
      turn these differences constrain visual short-term memory capacity.

PMID- 20680891
TI  - Lesions in the anterior thalamic nuclei of rats do not disrupt acquisition of
      stimulus sequence learning.
AB  - Sequence learning and spatial alternation were examined in rats with anterior
      thalamic lesions or sham surgeries. There was a lesion-induced deficit in spatial
      alternation but not in sequence learning. During sequence learning, rats
      discriminated between six different sequentially presented compounds (e.g.,
      reinforce A before B, but not B before A), composed of audio-visual elements. The
      solution required rats to learn both specific stimulus sequences and the reward
      contingencies associated with these specific temporal relationships. The failure
      of anterior thalamic lesions to affect the acquisition of this sequential
      configural task complements the recent finding that anterior thalamic lesions
      also spare the acquisition of a configural task involving specific stimulus
      pairings and their spatial relationships. These findings suggest that such
      "structural" learning is more reliant on cortico-hippocampal than thalamo
      hippocampal interactions.

PMID- 20680892
TI  - Strong and long: effects of word length on phonological binding in verbal short
      term memory.
AB  - This study examined the effects of item length on the contribution of linguistic
      knowledge to immediate serial recall (ISR). Long words are typically recalled
      more poorly than short words, reflecting the greater demands that they place on
      phonological encoding, rehearsal, and production. However, reverse word length
      effects--that is, better recall of long than short words--can also occur in
      situations in which phonological maintenance is difficult, suggesting that long
      words derive greater support from long-term lexical knowledge. In this study,
      long and short words and nonwords (containing one vs. three syllables) were
      presented for immediate serial recall in (a) pure lists and (b) unpredictable
      mixed lists of words and nonwords. The mixed-list paradigm is known to disrupt
      the phonological stability of words, encouraging their phonemes to recombine with
      the elements of other list items. In this situation, standard length effects were
      seen for nonwords, while length effects for words were absent or reversed. A
      detailed error analysis revealed that long words were more robust to the mixed
      list manipulation than short words: Their phonemes were less likely to be omitted
      and to recombine with phonemes from other list items. These findings support an
      interactive view of short-term memory, in which long words derive greater
      benefits from lexical knowledge than short words-especially when their
      phonological integrity is challenged by the inclusion of nonwords in mixed lists.

PMID- 20680893
TI  - If You Like the SGR ... You'll Love the IPAB.
AB  - Physicians hoped the health system reform law would eliminate the Sustainable
      Growth Rate (SGR) formula that drives down Medicare fees. The SGR, however,
      remains in place, and the law created a new board with the authority to cut fees
      even further, possibly on top of cuts under the SGR.

PMID- 20680894
TI  - Closing the 'pill mills': new state law requires certification.
AB  - A new law requires pain management clinics to be certified by the Texas Medical
      Board (TMB). The Texas Medical Association supported Senate Bill 911, which
      directs TMB to adopt rules to ensure quality of patient care and to set personnel
      requirements at pain management clinics. The new law also gives TMB authority to
      inspect pain management clinics, or entities believed to be pain management
      clinics, to determine whether they're operating legally.

PMID- 20680895
TI  - Quashing ownership: health reform law bans new physician-owned hospitals.
AB  - With nearly 70 Texas hospitals with some type of physician investment, the state
      is a national leader in the physician-owned hospital industry. And, members of
      that industry say it has been good for patients. But the health system reform law
      Congress passed earlier this year slams the door on new physician-owned hospitals
      by prohibiting them from obtaining a Medicare provider number.

PMID- 20680896
TI  - Move Into a SHAC: Physicians Make School Health Advisory Councils Better.
AB  - School health advisory councils (SHACs), which advise Texas school districts on
      coordinated health programming and its impact on students' health and learning,
      can be models for school campuses and instrumental in shaping school health
      policy. Texas law requires all school districts to have a SHAC. Physician members
      can lend credibility and a wide knowledge base to SHACs.

PMID- 20680897
TI  - Losing the match game: few residency slots leave more graduates unmatched.
AB  - An increasing number of medical graduates in the country, particularly in Texas,
      are finding it hard to match to a residency program in their preferred specialty.
      While medical educators say there are various reasons for that, almost all point
      to a growing imbalance in the ratio of medical graduates to residency slots. That
      imbalance is particularly apparent in Texas, where the state offered fewer first
      year residency positions in 2010 than it had medical graduates.

PMID- 20680898
TI  - Mum's the Word: Feds Are Serious About Protecting Patients' Privacy.
AB  - The Health Information Technology for Economic and Clinical Health (HITECH) Act
      significantly changes HIPAA privacy and security policies that affect physicians.
      Chief among the changes are the new breach notification regulations, developed by
      the U.S. Department of Health and Human Services Office for Civil Rights. The
      Texas Medical Association has developed resources to help physicians comply with
      the new HIPAA regulations.

PMID- 20680899
TI  - Transforming your tube.

PMID- 20680900
TI  - Value and pitfalls of neurophysiological monitoring in thoracic and
      thoracoabdominal aortic replacement and endovascular repair.
AB  - BACKGROUND: The aim of our study was to analyze the neurophysiological monitoring
      method with regard to its potential problems during thoracic and thoracoabdominal
      aortic open or endovascular repair. Furthermore, preventive strategies to the
      main pitfalls with this method were developed. METHODS: Between 11/2000 and
      05/2007 in 97 cases open surgery or endovascular stentgraft-implantation was
      performed on the thoracic or thoracoabdominal aorta. Intraoperatively,
      neurophysiologic motor- and somatosensory-evoked potentials were monitored.
      RESULTS: Our cases were divided into four groups: event-free patients with normal
      potentials (A, 63 cases), with correlation of modified evoked potentials and
      neurological outcome (B, 14 cases), false-positive or false-negative results (C,
      4 cases), and medication interaction or technical issues (D, 16 cases). We
      observed a sensitivity of 93 % and a specificity of 96 % for the
      neurophysiological monitoring. CONCLUSIONS: Monitoring spinal cord function
      during surgical and endovascular interventions on the thoracic and
      thoracoabdominal aorta is necessary. It can be made more effective by precisely
      analyzing the interference factors of the neurophysiological monitoring method
      itself. Successful strategies of immediate troubleshooting could be identified.

PMID- 20680901
TI  - Elective Matsui-Kitamura stent graft repair for descending thoracic aortic
      aneurysm and chronic type-B aortic dissection.
AB  - BACKGROUND: The position of thoracic endovascular aortic repair (TEVAR) compared
      to open surgery of the thoracic aorta has changed. This study evaluates outcomes
      after TEVAR performed electively using our original Matsui-Kitamura stent graft
      (MKSG) to treat descending thoracic aortic aneurysms (dTAA) and chronic type-B
      aortic dissection (type-B AD), and elucidates the risk factors for postoperative
      spinal cord ischemia (SCI). METHODS: TEVAR was performed using an MKSG in 66
      patients (age: 70.8+/-9.2 years). The underlying etiology was atherosclerotic
      change in 39 patients, chronic type-B aortic dissection in 23 patients, and other
      in 4 patients. RESULTS: No perioperative deaths occurred. Three patients showed
      temporary paralysis due to postoperative SCI. Abdominal aortic aneurysm (AAA)
      surgery was a risk factor for postoperative SCI (P=0.04). The 5-year survival
      rate was 81.2%. CONCLUSION: The present study demonstrated that TEVAR of patients
      with dTAA and chronic type-B AD using an MKSG can be performed with high
      technical success rates and low rates of severe acute complications. AAA surgery
      was a risk factor for postoperative SCI.

PMID- 20680902
TI  - Early influence of valve-related anticoagulation on false lumen thrombosis in
      aortic dissection patients after stented elephant trunk surgery.
AB  - BACKGROUND: Aim of the study was to assess the influence of anticoagulation on
      the false lumen after a stented elephant trunk procedure with mechanical valve
      replacement for aortic dissection patients. METHODS: Between 2003 and 2008, 181
      out of 232 aortic dissection patients undergoing stented elephant trunk procedure
      concomitant with arch and/or proximal surgery were enrolled in this study. Fifty
      five patients received an aortic valve replacement (AVR) with mechanical
      prosthesis. Patients were divided into two groups: with and without AVR. The
      aorta was evaluated by CT, and the diameter ratios between the true lumen and the
      aorta were calculated and the extent of thrombosis of the false lumen was
      quantified. RESULTS: Follow-up CT study at one year showed a significant
      difference between groups, mainly in the diameter ratios of the stent and aorta
      at the same level (P=0.003, at the stent end). Accordingly, CT data after
      hospital discharge differed significantly with regard to the extent of false
      lumen thrombosis at the carina level (P=0.020, at one year). Over one year after
      surgery, the residual false lumen around the stent-graft achieved complete
      thrombosis obliteration in 87.3% of patients with AVR and in 98.4% without AVR
      (P=0.005). CONCLUSIONS: Valve-related anticoagulation is associated with delay in
      false lumen thrombosis around the stent-graft.

PMID- 20680903
TI  - Use of a carotid artery for arterial cannulation: side-related differences.
AB  - BACKGROUND: Cannulation of arch arteries (innominate, axillary or carotid) for
      arterial return during cardiopulmonary bypass is increasingly being used;
      however, the flow and pressure profile in the cannulated arteries remains
      unclear. The aim of this study was to evaluate the flow and pressure
      characteristics of arterial inflow through a carotid artery, especially with
      regard to operative and technical aspects, clinical outcomes, and side-related
      differences. METHODS: Between January 2005 and April 2008, 200 consecutive
      patients underwent elective aortic arch surgery at our facility. One hundred
      patients were assigned to undergo cannulation of the left and another 100 to
      undergo cannulation of the right carotid artery. Both groups were similar in
      terms of age, sex, and type of surgery. In all patients, arterial return was
      through a side-graft anastomosed to the carotid artery. The arterial line was
      also used for unilateral cerebral perfusion for brain protection during mild
      hypothermic circulatory arrest. The flow and pressure profiles in the arterial
      line and in the carotid artery were evaluated with regard to cardiopulmonary
      bypass flow rate and side of cannulation. RESULTS: No complications related to
      the cannulation of a carotid artery were observed. The arterial return was
      adequate in all patients, regardless of the side being cannulated. Because of low
      resistance (mean pressure<50 mmHg) in the carotid artery proximal to the inflow
      side-graft, the flow toward the aortic arch averaged 87+/-2% (range 84.4-92%) of
      the total flow volume (4.6+/-0.5 L/min), without a significant difference between
      the sides. However, the perfusion pressure in the arterial line was significantly
      higher when the left carotid artery was cannulated (216+/-30 mmHg vs. 205+/-30
      mmHg; P=0.013). There was also a significant difference in the pressure in the
      distal carotid arteries, which, compared to the systolic blood pressure prior to
      cardiopulmonary bypass, increased by 30+/-24 mmHg on the left and decreased by
      16+/-21 mmHg on the right (P<0.001). CONCLUSIONS: Both common carotid arteries
      are suitable for arterial cannulation; however, left-sided cannulation is
      associated with an increase in the pressure profile. Therefore, if vascular
      pathology does not dictate cannulation of the left carotid artery, the right
      carotid artery should be considered the site of choice.

PMID- 20680904
TI  - Complicated acute type B dissections: a single-center experience with
      endovascular treatment.
AB  - BACKGROUND: Complicated acute type B dissections treated surgically carry a high
      risk of mortality. Endovascular interventions with stent-graft prostheses are a
      less invasive alternative and may obviate the need for surgery in most cases. We
      report here on our five years' experience with endovascular stenting in
      complicated acute type B dissections. PATIENTS AND METHODS: Between March 2001
      and January 2006, 32 patients (27 males, 5 females) with a mean age of 61.4+/
      11.32 years (range 29-80) underwent stent grafting for complicated acute type B
      dissections. Indications were progression of dissection with impending rupture
      (n=10), uncontrollable hypertension (n=9), intractable thoracic pain (n=7), and
      malperfusion syndrome (n=6). Talent-Medtronic (n=34) and Excluder-Gore (n=3)
      stent-grafts were used. In 5 patients two stents were necessary. In addition to
      stent grafting, aortic fenestration was performed in all three cases with lower
      limb ischemia. RESULTS: Endovascular stent placement was successful in all
      patients. Hospital mortality was 9.3% (3/32). No deaths occurred during follow-up
      (mean 32 months). CONCLUSION: Endovascular stenting of complicated acute type B
      dissections represents a safe alternative to surgery. Endovascular stent-grafts
      of appropriate sizes should be readily available in the hospital for emergency
      use, thus avoiding delays in treatment.

PMID- 20680905
TI  - Suppressing apoptosis with milrinone simulating extracorporeal circulation: a
      pilot study.
AB  - BACKGROUND: After cardioplegia, ischemia/reperfusion injury can induce apoptosis.
      The aim of this study was to evaluate our ex vivo microperfusion model on human
      myocardium during simulated cardioplegia (cp) and reperfusion (rep). In addition,
      the aim was to verify the anti-apoptotic properties of the phosphodiesterase 3
      inhibitor milrinone. METHODS: Cardiac biopsies were retrieved from the right
      auricle of patients undergoing elective CABG prior to induction of
      cardiopulmonary bypass. Biopsies were exposed to ex vivo conditions with varying
      periods of cp/rep (30/10, 60/20, 120/40 min). Group I consisted of untreated
      controls (n=15), Group II of treated controls who had cp/rep (n=15) while Group
      III had cp/rep+milrinone (n=15). For the detection of apoptosis, anti-activated
      caspase-3 and PARP-1 cleavage immunostaining were used. RESULTS: The percentage
      of apoptotic cardiomyocytes in Group I was significantly (P<0.05) lower compared
      to Group II, revealing a time-dependent increase. In Group III with milrinone
      treatment, apoptosis was significantly suppressed (P<0.05). CONCLUSIONS:
      Milrinone significantly suppressed apoptosis in our ex vivo setting. This finding
      warrants further study aiming to evaluate the potential beneficial effects of
      milrinone on the suppression of ischemia/reperfusion injury in a clinical
      setting.

PMID- 20680906
TI  - Surgical management of bronchiectasis: analysis of 277 patients.
AB  - BACKGROUND: Bronchiectasis is a permanent irreversible dilatation of the
      bronchial wall, often arising from inadequate treatment of a pulmonary infection.
      In recent years, the incidence of bronchiectasis has decreased mainly due to
      improved medical treatment of respiratory infections. However, the disease still
      constitutes a health problem in developing countries. METHOD: We reviewed 277
      patients with bronchiectasis who underwent pulmonary resection in the Ghaem &
      Omid hospitals affiliated to Mashhad University of Medical Sciences in Iran from
      1985 to 2008. The patients were evaluated for age, sex, clinical features,
      etiology, type of surgical procedure, morbidity, mortality and treatment
      outcomes. RESULTS: A total of 277 patients were enrolled in this study [200 males
      (72.2%) and 77 females (27.7%)]. Mean patient age was 34.7 years. The most common
      symptom was productive cough (79.4%). The most common etiology was pulmonary
      infection (77.6%). The disease was bilateral in 62 cases (22.3%) and the most
      common site of involvement was the left lower lobe (55%). The most common
      surgical technique for the unilateral form was lobectomy (42.2%) and one-sided
      lobectomy with segmentectomy of the other side in 25 patients with bilateral
      bronchiectasis. Mortality and morbidity rates were 0.7% and 15.8%, respectively.
      The most common complication was wound infection (5.7%). The mean follow-up was
      4.5 years. 68.5% of patients were symptom-free at the last postoperative
      evaluation, 23.8% had an improvement in their symptoms, and 7.5% of patients
      showed no improvement. Statistically, complete resection had a better outcome.
      CONCLUSION: In conclusion, surgery is an acceptable treatment in bronchiectasis
      and has low mortality and morbidity rates. The best outcomes were observed after
      complete resection. In selected bilateral cases, resection was used with
      acceptable outcomes.

PMID- 20680907
TI  - Isokinetic muscle strength after thoracotomy: standard vs. muscle-sparing
      posterolateral thoracotomy.
AB  - BACKGROUND: The aim of the study was to compare the effects of conventional
      posterolateral thoracotomy and muscle-sparing posterolateral thoracotomy on
      pulmonary and muscle strength. METHODS: From January 2003 to December 2004, 50
      randomized patients with a diagnosis of primary lung cancer underwent pulmonary
      resection. The patients were divided into two groups: Group I (n=25) underwent
      conventional posterolateral thoracotomy, while Group II (n=25) had muscle-sparing
      thoracotomy. The groups were compared in terms of shoulder abduction/adduction
      isokinetic muscle strength and respiratory muscle strength. RESULTS: A comparison
      of maximal expiratory pressure and maximal inspiratory pressure preoperatively
      and postoperatively and of maximal expiratory pressure and maximal inspiratory
      pressure preoperatively and at 3 months postoperatively showed statistically
      significant differences (P<0.05). CONCLUSION: For the preservation of muscle
      strength, especially in patients whose jobs involved manual work, muscle-sparing
      posterolateral thoracotomy should be the first choice rather than conventional
      thoracotomy. Moreover, if necessary, the latissimus dorsi muscle can be used more
      extensively as a flap after muscle-sparing posterolateral thoracotomy procedures.

PMID- 20680908
TI  - Allograft entrapment after lung transplantation: a simple solution using a
      pleurocutaneous catheter.
AB  - BACKGROUND: Chronic pleural effusion following lung transplantation (LTx) is
      often responsible for respiratory insufficiency and can lead to lung entrapment.
      Decortication carries considerable morbidity, and extended use of tube
      thoracostomy is not practical. We have utilized an indwelling pleurocutaneous
      catheter in the setting of intractable post-transplant effusion and have reviewed
      our experience to determine whether this strategy: 1) facilitates resolution of
      effusion, and 2) adequately palliates lung entrapment. METHODS: Twelve PleurX
      (Denver Biomedical, Golden, CO, USA) catheters were placed in 9 LTx patients (6
      unilateral, 3 bilateral) for refractory pleural effusions after standard tube
      thoracostomy drainage failed (12/12). Two-thirds of the patients (8/12) also had
      concomitant lung entrapment. RESULTS: There was no operative mortality. Median
      time from LTx to catheter placement was 79 days (range 21-769). Catheter use
      achieved the desired outcome in 11/12 placements. Catheters remained in place for
      a median of 86 days (range 35-190). Direct catheter-related complications
      included hemothorax (1) and empyema (1). CONCLUSION: Use of an indwelling
      pleurocutaneous catheter effectively achieves its intended goals of pleurodesis
      and management of entrapped lungs after LTx.

PMID- 20680909
TI  - Asymptomatic paraganglioma of the posterior mediastinum misdiagnosed until
      operation.
AB  - A 23-year-old female patient was treated for a posterior mediastinal tumor of
      unknown histology. Her systemic blood pressure increased rapidly to a critical
      level immediately after starting surgical manipulation of the tumor, which was
      suggestive of a hyperfunctioning pheochromocytoma. The tumor was removed after
      controlling the blood pressure and was histologically diagnosed as an extra
      adrenal pheochromocytoma. Further postoperative investigations showed the tumor
      to be a sporadic type through further postoperative investigations and the
      patient had subsequently an uneventful course.

PMID- 20680910
TI  - A case of G-CSF-producing invasive apical cancer resected following preoperative
      adjuvant therapy.
AB  - The patient was a 47-year-old male with the chief complaints of right shoulder
      pain and fever. A 10-cm mass was found to be present in the right pulmonary
      apical region on chest X-ray examination. The mass was diagnosed as a G-CSF
      producing invasive apical cancer and the patient underwent chemoradiotherapy
      followed by right upper lobectomy with combined resection of the chest wall, and
      lymph node dissection. A very small nodule was noted in the right frontal lobe on
      brain MRI before surgery, and the final diagnosis was pT3N0M1, stage IV lung
      adenocarcinoma. For the brain metastasis, gamma knife treatment and chemotherapy
      were performed after surgery, and there was no recurrence during 16 months after
      surgery. The prognosis for G-CSF-producing lung cancer and invasive apical cancer
      is poor. This was a rare and difficult case of lung cancer showing both
      characteristics of lung cancer.

PMID- 20680911
TI  - Complete clinical response to neoadjuvant chemotherapy in a 54-year-old male with
      Askin tumor.
AB  - Askin tumor is a tumor of the thoracopulmonary region that most commonly affects
      children and adolescents. These rare tumors are a form of primitive
      neuroectodermal tumor and typically carry a poor prognosis. Treatment is
      multimodal and consists of a combination of neoadjuvant chemotherapy, radical
      resection, and adjuvant chemo- and radiotherapy or all of the above. Surgery is
      advocated in most cases. We report a case of Askin tumor in a 54-year-old male
      who showed rapid and complete response to neoadjuvant chemotherapy. This allowed
      potentially radical surgery to be avoided. At one-year follow-up he remains
      disease-free.

PMID- 20680913
TI  - Alternative salvage technique during postcardiotomy electrical storm.
AB  - Cardiac electrical storm is generally treated with antiarrhythmic drugs,
      electrical cardioversion, or catheter ablation. However, these conservative
      treatment modalities are considered neither curative nor preventive with regard
      to recurrent arrhythmias in postoperative electrical storm after open heart
      surgery. We present a case of surgical ventricular assist device placement for
      postcardiotomy electrical storm in a 38-year-old patient.

PMID- 20680912
TI  - Traumatic diaphragmatic and aortic rupture: an emerging challenge.
AB  - We report a case of traumatic diaphragmatic and aortic rupture in a 27-year-old
      man after a vehicle accident. The patient underwent successful aortic replacement
      with a prosthetic graft and diaphragmatic suture. The patient died one month
      later secondary to rupture of the infected graft. Acute traumatic aortic rupture
      (TAR) and blunt diaphragmatic rupture (BDR) are life-threatening complications of
      blunt chest trauma; more than 80 % of patients with these lesions die at the site
      of accident and only a very small percentage of cases are transferred alive to
      the emergency unit. In patients with major blunt trauma, aortic rupture and
      diaphragmatic rupture must be systematically included in the differential
      diagnosis.

PMID- 20680914
TI  - Vagus nerve schwannoma in the middle mediastinum.
AB  - Intrathoracic neurogenic tumors are generally located in the posterior
      mediastinum. They usually arise from an intercostal nerve or a sympathetic chain.
      Tumors originating from the vagus nerve in the middle mediastinum are extremely
      rare. This report describes a patient with a huge intrathoracic schwannoma of the
      vagus nerve in the middle mediastinum and reviews the literature.

PMID- 20680915
TI  - Hypertrophic obstructive cardiomyopathy with Schmidt's syndrome: report of a
      case.
AB  - Schmidt's syndrome is an autoimmune disease, which can present as a complication
      of idiopathic Addison's disease and chronic thyroiditis (Hashimoto's disease),
      and may cause acute adrenal insufficiency in the presence of stress such as
      surgery. In this study, we report a patient with hypertrophic obstructive
      cardiomyopathy (HOCM) complicated by Schmidt's syndrome who did not develop any
      complications after surgery.

PMID- 20680917
TI  - Small-bowel metastasis of malignant melanoma: video capsule endoscopy appearance.

PMID- 20680918
TI  - Endoscopic retrieval method using a small grip-seal plastic bag for large
      colorectal resection specimens after endoscopic submucosal dissection.

PMID- 20680919
TI  - Congenital colonic stenosis diagnosed in adulthood.

PMID- 20680920
TI  - Peroral direct cholangioscopy for recurrent bile duct stones, using an ultrathin
      upper endoscope.

PMID- 20680921
TI  - Cholangiodrainage in Roux-en-Y-settings: implantation of large-caliber stents via
      single balloon enteroscopy.

PMID- 20680922
TI  - Commentary: a confusing Fusobacterium infection.

PMID- 20680923
TI  - Lemierre's syndrome mimicking leptospirosis.
AB  - Lemierre's syndrome is a suppurative thrombophlebitis involving the internal
      jugular vein, most commonly associated with Fusobacterium necrophorum, usually a
      complication of oropharyngeal infections. This syndrome is rare and is often
      overlooked. We present a case of sepsis mimicking initially severe leptospirosis
      (Weil's disease) due to acute febrile illness with multiorgan failure and
      hyperbilirubinemia. Finally, blood cultures revealed Fusobacterium necrophorum
      and computed tomography (CT) demonstrated bilateral pulmonary nodules and a
      thrombus in the right internal jugular vein. Early clinical suspicion is crucial
      so that appropriate diagnostic investigation and antibiotic therapy can be
      initiated to minimize the risk of life-threatening complications.

PMID- 20680924
TI  - Addressing the excess breast cancer mortality in Filipino women in Hawai'i
      through AANCART, an NCI community network program.
AB  - Filipino women are more likely to die of breast cancer than their major Asian
      American counterparts even though they do not have the highest incidence of that
      cancer. Analysis showed that they have a more advanced stage at the time of
      diagnosis and they have low rates of compliance to mammography guidelines, both
      of which factors may contribute to their high mortality rate. A broad based but
      targeted breast cancer awareness effort was directed to Filipino women, which
      included involving the media, the training of key community leaders, and the
      development of partnerships with health organizations with a like mission. After
      four years of effort, it was possible to demonstrate improvement in mammography
      rates in Filipino women that approached those of the general population in
      Hawai'i.

PMID- 20680925
TI  - Trends in alcohol use among Hawai'i adolescents.
AB  - It is important to review trends in youth alcohol use over time in order to
      effectively tailor prevention programs to address those trends. This article
      reviews data on alcohol use behaviors from the Centers for Disease Control and
      Prevention's Youth Risk Behavior Survey in Hawai'i from 1993 to 2007. Five
      alcohol use indicators were examined and stratified by grade level, from 9th
      grade through 12th grade. Significant drops in nearly all indicators are seen
      among 9th through 11th graders, but not among 12th graders. This suggests that
      Hawaii youth are responding well to anti-alcohol messaging as young teens, but a
      different approach may be needed to target older teens.

PMID- 20680926
TI  - Medical student research at the John A. Burns School of Medicine (JABSOM): the
      Research Interest Group.

PMID- 20680927
TI  - Recent developments in cigarette smoking cessation.

PMID- 20680928
TI  - A brief description of the Bethesda System for reporting thyroid fine needle
      aspirates.
AB  - Fine needle aspiration has become the most prominent, and the easiest way, to
      morphologically evaluate lesions of the thyroid. When done correctly, the
      sensitivity and specificity of thyroid aspirates for detecting malignancy is very
      high. Unfortunately, clinicians are sometimes confused by the terminology used in
      thyroid cytopathology reports. One way to mitigate confusion is for all
      pathologists to use the same diagnostic criteria and terminology. Standardized
      terminology for thyroid cytopathology reports has recently been proposed. The
      following article introduces the concept of the Bethesda System for reporting
      thyroid aspirates. Sample diagnoses are given to illustrate how thyroid
      cytopathology reports may appear using the Bethesda System.

PMID- 20680929
TI  - Biomarkers of inflammation, endothelial dysfunction and insulin resistance in
      adults of Inner Mongolia, China.
AB  - BACKGROUND: Low-grade chronic inflammation and endothelial dysfunction have been
      hypothesized to underlie the constellation of cardiometabolic risk factors,
      possibly by inducing insulin resistance. In the present study, we investigated
      associations between inflammation, endothelial dysfunction biomarkers and insulin
      resistance [measured by homeostasis model assessment of insulin resistance (HOMA
      IR)] in a large community population. METHODS: We conducted a cross-sectional
      study among 2589 participants aged 20 years and older in Inner Mongolia, China.
      Overnight fasting blood samples were obtained to measure the plasma glucose,
      serum insulin and biomarkers including C-reactive protein (CRP), soluble inter
      cellular adhesion molecule-1 (sICAM-1), soluble E-selectin (sE-selectin) and
      angiotensin II. RESULTS: Among the residents of Inner Mongolia, levels of C
      reactive protein (7.58 versus 5.63), soluble E-selectin (20.69 versus 17.93) and
      angiotensin II (51.80 versus 48.00) were all significantly higher in individuals
      with a higher HOMA-IR than in those with lower HOMA-IR. Higher HOMA-IR was also
      positively and significantly (p < 0.05) associated with higher C-reactive protein
      (odds ratio 1.47, 95% confidence interval 1.19, 1.82), and higher soluble E
      selectin (odds ratio 1.53, 95% confidence interval 1.24, 1.88), adjusted for
      multivariables. CONCLUSIONS: Elevated C-reactive protein and soluble E-selectin
      were associated with higher HOMA-IR among residents of Inner Mongolia. This study
      suggests that inflammation and endothelial dysfunction may relate to insulin
      resistance.

PMID- 20680930
TI  - Caregiver burden among poor caregivers of patients with cancer in an urban
      African setting.
AB  - OBJECTIVES: The nature and magnitude of the problems facing caregivers remain
      largely unknown in developing countries of the world. This study addresses these
      issues in a group of caregivers of patients with cancer in Zaria, Nigeria.
      METHOD: One hundred and three patients attending an oncology outpatient clinic at
      the Ahmadu Bello University Teaching Hospital were enrolled in the study with
      their caregivers. The caregivers were interviewed using the Socio-demographic
      data sheet, General Health Questionnaire-30 (GHQ-30) and Zarith Burden Interview
      (ZBI). A score of 4 or more in GHQ and scores above the median score of the
      sample in ZBI were considered a clinically significant level of psychological
      morbidity and a high level of burden, respectively. Data obtained were analyzed
      using the Statistical Package for Social Sciences Version 13 for Windows. All
      statistical tests of significance were carried out at 5% level of probability.
      RESULTS: The patients were 60 women whose mean age was 57. Of the 103 caregivers,
      60 (58%) were men and 43 (42%) were women. Their mean age was 37. Their mean ZBI
      and GHQ-30 scores were 29.16+/-12.8 (median = 25) and 3.67+/-3.01, respectively.
      A high level of burden was found in 49.5% (95% CI 39.9-59.1%) and psychological
      morbidity was found in 46.6% (95% CI 37.0-56.2%) of the caregivers. High levels
      of burden and psychological morbidity were significantly associated with absence
      of financial support. CONCLUSION: The study demonstrated a high level of
      caregiver burden, psychological morbidity and financial strain in family
      caregivers coming to the clinic with a relative who has cancer in an urban
      Nigerian setting.

PMID- 20680931
TI  - In vitro protective effects of Withania somnifera (L.) dunal root extract against
      hydrogen peroxide and beta-amyloid(1-42)-induced cytotoxicity in differentiated
      PC12 cells.
AB  - Withania somnifera L. Dunal (Solanaceae), also known as 'ashwagandha' in Sanskrit
      and as 'Indian ginseng', is used widely in Ayurvedic medicine as a nerve tonic
      and memory enhancer, with antiaging, antistress, immunomodulatory and antioxidant
      properties. There is a paucity of data on the potential neuroprotective effects
      of W. somnifera root, as traditionally used, against H(2)O(2)- and Abeta((1-42))
      induced cytotoxicity which are current targets for novel approaches to treat
      dementia, especially dementia of the Alzheimer's type (AD). In this study, an
      aqueous extract prepared from the dried roots of W. somnifera was assessed for
      potential protective effects against H(2)O(2)- and Abeta((1-42))-aggregated
      fibril cytotoxicity by an MTT assay using a differentiated rat pheochromocytoma
      PC12 cell line. The results suggest that pretreatments of differentiated PC12
      cells with aqueous extracts of W. somnifera root significantly protect
      differentiated PC12 cells against both H(2)O(2)- and Abeta((1-42))-induced
      cytotoxicity, in a concentration dependent manner. To investigate the compounds
      that could explain the observed effects, the W. somnifera extract was analysed by
      liquid chromatography-serial mass spectrometry and numerous withanolide
      derivatives, including withaferin A, were detected. These results demonstrate the
      neuroprotective properties of an aqueous extract of W. somnifera root and may
      provide some explanation for the putative ethnopharmacological uses of W.
      somnifera for cognitive and other neurodegenerative disorders that are associated
      with oxidative stress.

PMID- 20680932
TI  - Determination of galanthamine in Bulbus Lycoridis Radiatae by coupling capillary
      electrophoresis with end-column electrochemiluminescence detection.
AB  - A novel method for the determination of galanthamine (GAL) in Bulbus Lycoridis
      Radiatae has been developed based on coupling CE with an end-column tris(2,2'
      bipyridyl)ruthenium(II) electrochemiluminescence (ECL). Parameters affecting CE
      separation and ECL detection were investigated and optimized. Baseline separation
      of GAL from other components in the Bulbus Lycoridis Radiatae sample was achieved
      with an 18 mmol/L phosphate running buffer at pH 9.0. Under the optimized
      conditions: 12 kV CE-separation voltage, ECL detection potential at 1.25 V with 5
      mmol/L Ru(bpy)(3)(2+) and 50 mmol/L phosphate buffer at pH 7.5 in the detection
      reservoir, the linear range of GAL concentration was from 0.8 ng/mL to 2
      microg/mL, whereas the detection limit was 0.25 ng/mL (S/N=3). The proposed
      method was successfully demonstrated for the determination of GAL in Bulbus
      Lycoridis Radiatae.

PMID- 20680933
TI  - Exploring reversible quenching of fluorescence from a pyrazolo[3,4-b]quinoline
      derivative by protonation.
AB  - Pyrazolo[3,4-b]quinoline derivatives are reported to be highly efficient organic
      fluorescent materials suitable for applications in light-emitting devices.
      Although their fluorescence remains stable in organic solvents or in aqueous
      solution even in the presence of H(2)O, halide salts (LiCl), alkali (NaOH) and
      weak acid (acetic acid), it suffers an efficient quenching process in the
      presence of protic acid (HCl) in aqueous or ethanolic solution. This quenching
      process is accompanied by a change in the UV spectrum, but it is reversible and
      can be fully recovered. Both steady-state and transient fluorescence spectra of 1
      phenyl-3,4-dimethyl-1H-pyrazolo-[3,4-b]quinoline (PAQ5) during quenching are
      measured and analyzed. It is found that a combined dynamic and static quenching
      mechanism is responsible for the quenching processes. The ground-state proton
      transfer complex [PAQ5H(+)] is responsible for static quenching. It changes
      linearly with proton concentration [H(+)] with a bimolecular association constant
      K(S)=1.95 M(-1) controlled by the equilibrium dissociation of HCl in ethanol. A
      dynamic quenching constant K(D)=22.4 M(-1) is obtained by fitting to the Stern
      Volmer equation, with a bimolecular dynamic quenching rate constant
      k(d)=1.03x10(9) s(-1) M(-1) under ambient conditions. A change in electron
      distribution is simulated and explains the experiment results.

PMID- 20680934
TI  - Double-bond versus triple-bond bridges: does it matter for the charge-transfer
      absorption by donor-acceptor chromophores?

PMID- 20680935
TI  - Intertorsional interactions revealing absolute configurations: the V6 internal
      rotation heavy-top case of benzotrifluoride.
AB  - The microwave spectroscopic signatures of multiple torsional states of the CF(3)
      internal rotation in benzotrifluoride (alpha,alpha,alpha-trifluorotoluene) are
      reported. Individual rotational transitions are observed in a total of eight
      different torsional states, a quite challenging task for heavy tops even with
      Fourier transform microwave techniques. Accidental mixings of m = 0 and m = 3
      torsional states as well as m = 1 and m = 2 torsional states, which can
      complicate the assignment of the spectra severely, are observed. These accidental
      mixings are probably systematic for molecules with heavy tops exhibiting an
      almost free internal rotation, and give an opportunity to determine the sign in
      the (1/2) V(6) (1+/-cos6tau) potential function hindering internal rotation and
      in consequence the orientation of the CF(3) top versus C(6)H(5) frame. A recently
      developed torsion-rotation program reproduces all line positions within an
      experimental accuracy of about 2.0 kHz. The V(6) barrier is determined to be
      3.229949(32) cm(-1). The corresponding torsional spacings are determined with the
      seven-digit accuracy underlying the supersonic-jet Fourier transform microwave
      technique.

PMID- 20680936
TI  - Electro-optical gas sensor based on a planar light-emitting electrochemical cell
      microarray.

PMID- 20680937
TI  - Pyrene-based fluorescent nitric oxide cheletropic traps (FNOCTs) for the
      detection of nitric oxide in cell cultures and tissues.
AB  - The synthesis and the structural and spectroscopic characterization of
      nonfluorescent, pyrene-based cyclic o-quinodimethanes are reported. These
      compounds react efficiently with nitric oxide (NO) in a formal cheletropic
      manner, by which the fluorescent aromatic pyrene system is regenerated. The NO
      trapping capabilities and kinetics of the fluorescent nitric oxide cheletropic
      traps (FNOCTs) are assessed in THF and buffered aqueous solution by ESR, UV/Vis,
      and fluorescence spectroscopy, by employing NO solutions and NO released from N
      diazeniumdiolates (NONOates). Prototypal biological applications include the
      quantitation of NO production from cultured rat alveolar macrophages and the
      endothelium of porcine aorta, which demonstrate a sensitivity for NO detection in
      the nanomolar range.

PMID- 20680938
TI  - AT-specific DNA binding of binuclear ruthenium complexes at the border of
      threading intercalation.
AB  - The binuclear ruthenium complex [MU-bidppz(phen)(4)Ru(2)](4+) has been
      extensively studied since the discovery of its unusual threading intercalation
      interaction with DNA, a binding mode with extremely slow binding and dissociation
      kinetics. The complex has been shown to be selective towards long stretches of
      alternating AT base pairs, which makes it interesting, for example, as a model
      compound for anti-malaria drugs due to the high AT content of the genome of the
      malaria parasite P. falciparum. We have investigated the effect of bridging
      ligand structure on threading intercalation ability and found that length and
      rigidity as well as the size of the intercalated ring system are all factors that
      affect the rate and selectivity of the threading intercalation. In particular, we
      discovered a new DNA-threading compound, [MU-dppzip(phen)(4)Ru(2)](4+), which
      appears to be just at the border of being capable of threading intercalation and
      displays even greater selectivity for AT-DNA than the parent compound, [MU
      bidppz(phen)(4)Ru(2)](4+).

PMID- 20680939
TI  - Studies on the reactivity of [Ge9]4- towards [Fe(cot)(CO)3]: synthesis and
      characterization of [Ge8Fe(CO)3]3- and of the anionic organometallic species
      [Fe(cot)(CO)3]-.
AB  - Reaction of cyclooctatetraene (COT) iron(II) tricarbonyl, [Fe(cot)(CO)(3)], with
      one equivalent of K(4)Ge(9) in ethylenediamine (en) yielded the cluster anion
      [Ge(8)Fe(CO)(3)](3-) which was crystallographically-characterized as a [K(2,2,2
      crypt)](+) salt in [K(2,2,2-crypt)](3)[Ge(8)Fe(CO)(3)]. The chemically-reduced
      organometallic species [Fe(eta(3)-C(8)H(8))(CO)(3)](-) was also isolated as a
      side-product from this reaction as [K(2,2,2-crypt)][Fe(eta(3)-C(8)H(8))(CO)(3)].
      Both species were further characterized by EPR and IR spectroscopy and
      electrospray mass spectrometry. The [Ge(8)Fe(CO)(3)](3-) cluster anion represents
      an unprecedented functionalized germanium Zintl anion in which the nine-atom
      precursor cluster has lost a vertex, which has been replaced by a transition
      metal moiety.

PMID- 20680941
TI  - Azaphenalene phthalocyanines: phthalocyanine analogues with six-membered-ring
      units instead of five-membered-ring units.
AB  - Mixed-condensation reaction of 1,8-naphthalenedicarbonitrile and a 4,5
      disubstituted phthalonitrile provided a series of phthalocyanine (Pc) analogues
      with azaphenalene (AP) moieties in place of the isoindole moieties.
      Monosubstituted species, APPc, and the two structural isomers of disubstituted
      species, adj-AP(2)Pc and opp-AP(2)Pc, were successfully isolated by gel
      permeation chromatography on HPLC apparatus. Their structures were elucidated by
      (1)H NMR spectroscopy and X-ray crystallographic analysis. Replacement of the
      isoindole moieties with azaphenalene moieties created six-membered-ring units in
      the core and caused distortion of the molecular structures. The Q-band absorption
      shifted to the red upon an increase in the number of azaphenalene units; the
      shape of the absorption spectra depended on the molecular symmetries. APPc and
      opp-AP(2)Pc showed a large splitting of the Q band, whereas adj-AP(2)Pc exhibited
      a single broad Q band. These changes in the absorption spectra, as well as the
      unique electronic structures, are discussed in detail, based on magnetic circular
      dichroism spectra, electrochemical measurements, and density functional theory
      calculations.

PMID- 20680940
TI  - Curvularides A-E: antifungal hybrid peptide-polyketides from the endophytic
      fungus Curvularia geniculata.
AB  - Five new hybrid peptide-polyketides, curvularides A-E (1-5), were isolated from
      the endophytic fungus Curvularia geniculata, which was obtained from the limbs of
      Catunaregam tomentosa. Structure elucidation for curvularides A-E (1-5) was
      accomplished by analysis of spectroscopic data, as well as by single-crystal X
      ray crystallography. Curvularide B (2) exhibited antifungal activity against
      Candida albicans, and it also showed synergistic activity with a fluconazole
      drug.

PMID- 20680942
TI  - Cobalt coordination and clustering in alpha-Co(OH)(2) revealed by synchrotron X
      ray total scattering.
AB  - Structures of layered metal hydroxides are not well described by traditional
      crystallography. Total scattering from a synthesis-controlled subset of these
      materials, as described here, reveals that different cobalt coordination
      polyhedra cluster within each layer on short length scales, offering new insights
      and approaches for understanding the properties of these and related layered
      materials. Structures related to that of brucite [Mg(OH)(2)] are ubiquitous in
      the mineral world and offer a variety of useful functions ranging from catalysis
      and ion-exchange to sequestration and energy transduction, including applications
      in batteries. However, it has been difficult to resolve the atomic structure of
      these layered compounds because interlayer disorder disrupts the long-range
      periodicity necessary for diffraction-based structure determination. For this
      reason, traditional unit-cell-based descriptions have remained inaccurate. Here
      we apply, for the first time to such layered hydroxides, synchrotron X-ray total
      scattering methods-analyzing both the Bragg and diffuse components-to resolve the
      intralayer structure of three different alpha-cobalt hydroxides, revealing the
      nature and distribution of metal site coordination. The different compounds with
      incorporated chloride ions have been prepared with kinetic control of hydrolysis
      to yield different ratios of octahedrally and tetrahedrally coordinated cobalt
      ions within the layers, as confirmed by total scattering. Real-space analyses
      indicate local clustering of polyhedra within the layers, manifested in the
      weighted average of different ordered phases with fixed fractions of
      tetrahedrally coordinated cobalt sites. These results, hidden from an averaged
      unit-cell description, reveal new structural characteristics that are essential
      to understanding the origin of fundamental material properties such as color,
      anion exchange capacity, and magnetic behavior. Our results also provide further
      insights into the detailed mechanisms of aqueous hydrolysis chemistry of hydrated
      metal salts. We emphasize the power of the methods used here for establishing
      structure-property correlations in functional materials with related layered
      structures.

PMID- 20680943
TI  - Tripodal thiols as ligands for molecular magnets: very strong antiferromagnetic
      exchange interactions in vanadium(III) clusters.
AB  - The synthesis, structural and magnetic characterisation of
      [V(III)(3)O(tmme)(2)(diimine)(2)Cl] [diimine=2,2'-bipyridine (1) or 1,10
      phenanthroline (2)] and (HNEt(3))(2)[V(III)(4)O(tmme)(4)] (3) is reported, in
      which H(3)tmme is tris(mercaptomethyl)ethane, MeC(CH(2)SH)(3), the thiol analogue
      of the famous tripodal alcohol ligands typified by H(3)thme
      [tris(hydroxymethyl)ethane, MeC(CH(2)OH)(3)]. Complexes 1 and 3 have "T-shaped"
      and square topologies, respectively, and the latter is centred on a rare example
      of a square-planar oxide. The tri-thiolate ligands bind the periphery of the
      clusters and provide such strong antiferromagnetic exchange pathways that in both
      cases only a single total spin state is occupied up to room temperature, in the
      absence of metal-metal bonding. Magnetic data, electronic structure calculations
      and electrochemical data are reported.

PMID- 20680944
TI  - Synthetic studies on and mechanistic insight into [W(CO)5(L)]-catalyzed
      stereoselective construction of functionalized bicyclo[5.3.0]decane frameworks.
AB  - Stereoselective preparation of a variety of synthetically useful functionalized
      bicyclo[5.3.0]decane derivatives was achieved by tandem cyclization of 3-siloxy
      1,3,9-triene-7-yne derivatives based on the electrophilic activation of alkynes
      catalyzed by [W(CO)(5)(L)]. The reaction proceeded smoothly under
      photoirradiation, and various substrates were cyclized to give the corresponding
      bicyclic compounds with up to four chiral centers stereospecifically. Reactions
      of siloxydienes with a silyl substituent as an equivalent of a hydroxyl group
      also proceeded with wide generality to afford silyl-substituted
      bicyclo[5.3.0]decanes, which were highly useful as synthetic intermediates.
      Stereochemical studies concerning the silyl enol ether moiety suggested that two
      types of reaction pathway for the formation of seven-membered rings were present.
      The reaction of (Z)-enol silyl ethers proceeded through Cope rearrangement of cis
      divinylcyclopropane intermediates, and that of (E)-enol silyl ethers by 1,4
      addition of the dienyl tungsten species at the position delta to the metal atom.
      In the reactions of siloxydiene derivatives with silyl substituents, all possible
      diastereomers could be synthesized stereoselectively by changing the geometry of
      the silyl enol ether and enyne moieties.

PMID- 20680945
TI  - Platinum nanoflowers on scratched silicon by galvanic displacement for an
      effective SALDI substrate.
AB  - We report a new and facile method for synthesizing 3D platinum nanoflowers (Pt
      Nfs) on a scratched silicon substrate by electroless galvanic displacement and
      discuss the applications of the Pt Nfs in surface-assisted laser
      desorption/ionization-mass spectrometry (SALDI-MS). Surface scratching of n-type
      silicon is essential to induce Pt Nf growth on a silicon substrate (to obtain a
      Pt Nf silicon hybrid plate) by the galvanic displacement reaction. The Pt Nf
      silicon hybrid plate showed excellent SALDI activity in terms of the efficient
      generation of protonated molecular ions in the absence of a citrate buffer. We
      propose that the acidity of the Si-OH moieties on silicon increases because of
      the electron-withdrawing nature of the Pt Nfs; hence, proton transfer from the Si
      OH groups to the analyte molecules is enhanced, and finally, thermal desorption
      of the analyte ions from the surface occurs. Signal enhancement was observed for
      protonated molecular ions produced from a titania nanotube array (TNA) substrate
      on which Pt nanoparticles had been photochemically deposited. Moreover, surface
      modification of the Pt Nf silicon hybrid plate by perfluorodecyltrichlorosilane
      (FDTS) (to obtain an FDTS-Pt Nf silicon hybrid plate) was found to facilitate
      soft SALDI of labile compounds. More interestingly, the FDTS-Pt Nf silicon hybrid
      plate acts 1) as a high-affinity substrate for phosphopeptides and 2) as a SALDI
      substrate. The feasibility of using the FDTS-Pt Nf silicon hybrid plate for SALDI
      MS has been demonstrated by using a beta-casein digest and various analytes,
      including small molecules, peptides, phosphopeptides, phospholipids,
      carbohydrates, and synthetic polymers. The hybridization of Pt Nfs with a
      scratched silicon substrate has been found to be important for achieving
      excellent SALDI activity.

PMID- 20680946
TI  - Enantiomerically pure alleno-acetylenic macrocycles: synthesis, solid-state
      structures, chiroptical properties, and electron localization function analysis.
AB  - New enantiomerically pure alleno-acetylenic macrocycles were prepared by
      oxidative homocoupling of optically active 1,3-diethynylallenes. Enantiomer
      separation resulted from a combined strategy of synthesis and chiral HPLC
      techniques. Two other achiral stereoisomers were also isolated and fully
      characterized. In addition, the X-ray structures of the chiral D(4)- and C(2)
      symmetric macrocycles are reported. The chiroptical properties of these
      macrocycles are discussed on the basis of quantum chemical calculations, by using
      the CAM-B3LYP functional. Studies were carried out to investigate the vibronic
      fine structure observed experimentally in the UV/Vis and CD spectra. The origin
      of the intense chiroptical response of the chiral alleno-acetylenic macrocycles
      is explained by considering the topology of the molecular orbitals involved, thus
      relating electronic properties to structural features. Further analysis of the
      canonical molecular orbitals and the electron localization function (ELF) shows
      that these macrocycles belong to a relatively rare class of highly stable and
      formally anti-aromatic Huckel compounds.

PMID- 20680947
TI  - Deboronation and deprotonation of ortho-carborane with N-heterocyclic carbenes.

PMID- 20680948
TI  - Dispersing carbon nanotubes with graphene oxide in water and synergistic effects
      between graphene derivatives.

PMID- 20680949
TI  - Molecular [Yb(TM)2] intermetalloids (TM=Ru, Re).

PMID- 20680950
TI  - Electrochemical characterization of a single electricity-producing bacterial cell
      of Shewanella by using optical tweezers.

PMID- 20680951
TI  - Directional proton transfer in membrane proteins achieved through protonated
      protein-bound water molecules: a proton diode.

PMID- 20680952
TI  - Hydrogen-atom tunneling could contribute to H2 formation in space.

PMID- 20680953
TI  - Metal-rich copper chalcogenide clusters at the border between molecule and bulk
      phase: the structures of [Cu93Se42(SeC6H4SMe)9(PPh3)18],
      [Cu96Se45(SeC6H4SMe)6(PPh3)18], and [Cu136S56(SCH2C4H3O)24(dpppt)10].

PMID- 20680954
TI  - Quantitative CARS molecular fingerprinting of single living cells with the use of
      the maximum entropy method.

PMID- 20680955
TI  - Efficient production of the liquid fuel 2,5-dimethylfuran from fructose using
      formic acid as a reagent.

PMID- 20680956
TI  - Water-soluble supramolecular polymerization driven by multiple host-stabilized
      charge-transfer interactions.

PMID- 20680957
TI  - Highly specific heterodimerization mediated by quadrupole interactions.

PMID- 20680958
TI  - High-surface-area silica nanospheres (KCC-1) with a fibrous morphology.

PMID- 20680960
TI  - Loss of Bright/ARID3a function promotes developmental plasticity.
AB  - B-cell regulator of immunoglobulin heavy chain transcription (Bright)/ARID3a, an
      A+T-rich interaction domain protein, was originally discovered in B lymphocyte
      lineage cells. However, expression patterns and high lethality levels in knockout
      mice suggested that it had additional functions. Three independent lines of
      evidence show that functional inhibition of Bright results in increased
      developmental plasticity. Bright-deficient cells from two mouse models expressed
      a number of pluripotency-associated gene products, expanded indefinitely, and
      spontaneously differentiated into cells of multiple lineages. Furthermore, direct
      knockdown of human Bright resulted in colonies capable of expressing multiple
      lineage markers. These data suggest that repression of this single molecule
      confers adult somatic cells with new developmental options.

PMID- 20680961
TI  - Notch activation differentially regulates renal progenitors proliferation and
      differentiation toward the podocyte lineage in glomerular disorders.
AB  - Glomerular diseases account for 90% of end-stage kidney disease. Podocyte loss is
      a common determining factor for the progression toward glomerulosclerosis. Mature
      podocytes cannot proliferate, but recent evidence suggests that they can be
      replaced by renal progenitors localized within the Bowman's capsule. Here, we
      demonstrate that Notch activation in human renal progenitors stimulates entry
      into the S-phase of the cell cycle and cell division, whereas its downregulation
      is required for differentiation toward the podocyte lineage. Indeed, a persistent
      activation of the Notch pathway induced podocytes to cross the G(2)/M checkpoint,
      resulting in cytoskeleton disruption and death by mitotic catastrophe. Notch
      expression was virtually absent in the glomeruli of healthy adult kidneys, while
      a strong upregulation was observed in renal progenitors and podocytes in patients
      affected by glomerular disorders. Accordingly, inhibition of the Notch pathway in
      mouse models of focal segmental glomerulosclerosis ameliorated proteinuria and
      reduced podocyte loss during the initial phases of glomerular injury, while
      inducing reduction of progenitor proliferation during the regenerative phases of
      glomerular injury with worsening of proteinuria and glomerulosclerosis. Taken
      altogether, these results suggest that the severity of glomerular disorders
      depends on the Notch-regulated balance between podocyte death and regeneration
      provided by renal progenitors.

PMID- 20680962
TI  - Outsourcing of ultrasound services in obstetrics and gynecology.

PMID- 20680963
TI  - Characterization of de novo transcriptome for waterhemp (Amaranthus tuberculatus)
      using GS-FLX 454 pyrosequencing and its application for studies of herbicide
      target-site genes.
AB  - BACKGROUND: Waterhemp is a model for weed genomics research in part because it
      possesses many interesting biological characteristics, rapidly evolves resistance
      to herbicides and has a solid foundation of previous genetics work. To develop
      further the genomics resources for waterhemp, the transcriptome was sequenced
      using Roche GS-FLX 454 pyrosequencing technology. RESULTS: Pyrosequencing
      produced 483 225 raw reads, which, after quality control and assembly, yielded 44
      469 unigenes (contigs + singletons). A total of 49% of these unigenes displayed
      highly significant similarities to Arabidopsis proteins and were subsequently
      grouped into gene ontology categories. Blast searches against public and custom
      databases helped in identifying and obtaining preliminary sequence data for all
      of the major target-site genes for which waterhemp has documented resistance.
      Moreover, sequence data for two other herbicide targets [4-hydroxyphenylpyruvate
      dioxygenase (HPPD) and glutamine synthetase], where resistance has not yet been
      reported in any plant, were also investigated in waterhemp and six related weedy
      Amaranthus species. CONCLUSION: These results demonstrate the enormous value of
      454 sequencing for gene discovery and polymorphism detection in a major weed
      species and its relatives. Furthermore, the merging of the 454 transcriptome data
      with results from a previous whole genome 454 sequencing experiment has made it
      possible to establish a valuable genomic resource for weed science research.

PMID- 20680964
TI  - Activation of the mammalian target of rapamycin signaling pathway in
      hepatocellular carcinoma.

PMID- 20680965
TI  - Inhibition of Bcl-2 and Bcl-X enhances chemotherapy sensitivity in hepatoblastoma
      cells.
AB  - BACKGROUND: An increased expression of anti-apoptotic proteins is regularly found
      in malignant cells, contributing to their clonal expansion by conferring an
      improved survival ability. In Hepatoblastoma (HB) apoptosis regulation
      contributes to resistance and therapy failure, therefore we modulated apoptosis
      sensitivity of HB cells for an improved cytotoxic activity of commonly used
      drugs. PROCEDURE: Apoptosis-related proteins were quantified in HB cells (HuH6
      and HepT1) using protein assays. Interaction of ABT-737, a small-molecule
      inhibitor of Bcl-2, Bcl-xL, and Bcl-W with cytotoxic drugs was monitored in a
      proliferation assay. Apoptosis induction was measured by caspase-3 activity.
      RESULTS: We found high levels of the anti-apoptotic protein Bcl-2 and Bcl-X as
      well as low levels of pro-apoptotic protein Bax and Bad in both HB cell lines.
      ABT-737 induced apoptosis in HuH6 and HepT1 cells at concentrations higher than 1
      uM. ABT-737 also enhanced the cytotoxic effect of cisplatin (CDDP), doxorubicin
      (DOXO), etoposide and paclitaxel when used as combination therapy. HuH6 expressed
      slightly higher pro-apoptotic and lower anti-apoptotic protein levels than HepT1,
      which may explain the stronger enhancement of cytostatic drug effects in HuH6
      cells when treated in combination with ABT-737. CONCLUSION: The observed anti
      apoptotic phenotype in HB cell lines may contribute to resistance to cytotoxic
      drugs used in the standard treatment protocol of HB. These pre-clinical results
      suggest that apoptosis sensitizers with BH-3 mimicry, such as ABT-737, should be
      further evaluated in preclinical models of HB.

PMID- 20680966
TI  - Oncostatin M synergistically induces CXCL10 and ICAM-1 expression in IL-1beta
      stimulated-human gingival fibroblasts.
AB  - Periodontitis is a chronic bacterial infection of tooth-supporting structures. T
      helper type 1 (Th1) cells are related to the exacerbation of periodontal disease.
      Human gingival fibroblasts (HGFs), the major cell type in periodontal connective
      tissues, are involved in immunological response in periodontal tissues. However,
      it is uncertain whether HGFs are related to Th1 response. Chemokine (C-X-C motif)
      ligand 10 (CXCL10) is a cytokine, that is related to Th1 cells migration.
      Intercellular adhesion molecule (ICAM)-1 is involved in Th1 cells retention and
      activation in inflamed tissue. The aim of this study is to examine the effect of
      oncostatin M (OSM) on CXCL10 and ICAM-1 expression in HGFs. OSM stimulation
      induced CXCL10 and ICAM-1 expression in HGFs. Moreover, the synergistic effects
      of CXCL10 release and ICAM-1 expression in HGFs were observed with combined
      stimulation of interleukin (IL)-1beta and OSM. OSM increased type 1 IL-1 receptor
      (IL-1R1) expression, and IL-1beta enhanced OSMRbeta expression on HGFs. IL-1beta
      + OSM stimulation enhanced the phosphorylation of inhibitor of nuclear factor
      kappaB (IkappaB)-alpha, signal transducer and activator of transcription (STAT)3,
      c-Jun N terminal kinase (JNK), and protein kinase B (Akt) compared to OSM or IL
      1beta stimulation. CXCL10 production from OSM + IL-1beta stimulated HGFs was
      suppressed by nuclear factor (NF)-kappaB, STAT3, JNK, and phosphoinositide-3
      kinase (PI3K) inhibitors. On the other hand, only NF-kappaB and STAT3 inhibitors
      suppressed ICAM-1 expression enhanced by OSM + IL-1beta treatment. These effects
      of OSM and IL-1beta may promote Th1 cells infiltration and retention in
      periodontally diseased tissues and be related to exacerbation of periodontal
      disease.

PMID- 20680967
TI  - Framework and methodology for evaluating mental health policy and plans.
AB  - The importance of monitoring and evaluation for mental health service planning
      and delivery is indubitable. Notwithstanding, monitoring and evaluation of mental
      health policy and plans has received only limited attention. This paper presents
      an approach developed by the World Health Organization for monitoring mental
      health policy and plans that can be adapted and utilized for evaluation and
      monitoring of policy and plans in most other health spheres as well. Four
      critical areas are outlined i.e., evaluation of the policy document and the plan
      derived from it; monitoring the implementation of the strategic plan; evaluation
      of the implementation of the plan; and evaluation of whether the objectives of
      the policy have been achieved. Overcoming difficulties in objective assessment of
      policy documents and plans is discussed and two WHO checklists for evaluating the
      process, content and operational aspects of policies and plans are introduced
      together with a five step guidance process for conducting policy and plan
      evaluations.

PMID- 20680968
TI  - Incidence of bacteremias and invasive mycoses in children with acute non
      lymphoblastic leukemia: results from a multi-center Italian study.
AB  - BACKGROUND: Data on the epidemiology of bacteremias and invasive fungal diseases
      (IFD) in children with acute myeloid leukemia (AML) are scarce. DESIGN AND
      METHODS: In a multi-center, retrospective study, we analyzed proportion, rate per
      1,000 person-days at risk, and cumulative risk of bacteremias and IFD in children
      with AML. RESULTS: Between January 1998 and December 2005, 240 children were
      treated for AML at 8 Italian Centers, for a total of 521 treatment courses and
      63,232 person-days at risk. Bacteremia was observed in 32% of treatment courses
      and IFD was seen in 10% (P < 0.0001), with rates of 2.62 and 0.84, respectively
      (P < 0.001). There was a significantly higher frequency of IFD during relapse
      treatment: proportion 15% versus 9% (P = 0.05), rate 2.10 versus 0.64 (P = 0.008)
      and cumulative risk 32% versus 12% (P = 0.007), while there were no differences
      in the proportion, rate and cumulative risk of bacteremia during front-line or
      relapse treatment. The epidemiology of bacteremias and IFD was different during
      front-line therapy for M3 as compared to other types of AML, but the differences
      were not statistically significant. CONCLUSIONS: Severe infectious complications
      are frequent during the treatment of pediatric AML, especially during relapse
      treatment, and bacteremias are more frequent than IFD.

PMID- 20680969
TI  - Interactions of hemoglobin in live red blood cells measured by the
      electrophoresis release test.
AB  - To elucidate the protein-protein interactions of hemoglobin (Hb) variants A and
      A(2), HbA was first shown to bind with HbA(2) in live red blood cells (RBCs) by
      diagonal electrophoresis and then the interaction between HbA and HbA(2) outside
      the RBC was shown by cross electrophoresis. The starch-agarose gel
      electrophoresis of hemolysate, RBCs, freeze-thawed RBCs and the supernatant of
      freeze-thawed RBCs showed that the interaction between HbA and HbA(2) was
      affected by membrane integrity. To identify the proteins involved in the
      interaction, protein components located between HbA and HbA(2) in RBCs (RBC HbA
      HbA(2)) and hemolysate (hemolysate HbA-HbA(2)) were isolated from the starch
      agarose gel and separated by 5-12% SDS-PAGE. The results showed that there was a
      ~22 kDa protein band located in the RBC HbA-HbA(2) but not in hemolysate HbA
      HbA(2). Sequencing by LC/MS/MS showed that this band was a protein complex that
      included mainly thioredoxin peroxidase B, alpha-globin, delta-globin and beta
      globin. Thus, using our unique in vivo whole blood cell electrophoresis release
      test, Hbs were proven for the first time to interact with other proteins in the
      live RBC.

PMID- 20680970
TI  - Determination of unconjugated aromatic acids in urine by capillary
      electrophoresis with dual electrochemical detection--potential application in
      fast diagnosis of phenylketonuria.
AB  - A novel method of CE coupled with dual electrochemical detection has been
      developed for the determination of pathological metabolites of phenylalanine in
      urine samples. Factors influencing the separation and detection were examined and
      optimized. Five aromatic acid metabolites and a major coexisting interfering
      compound uric acid could be well separated within 23 min at a separation voltage
      of 16 kV using a 35 mmol/L SDS/60 mmol/L H(3)BO(3)-Na(2)B(4)O(7) running buffer
      (pH 8.2). Highly linear response was obtained for these five biomarker compounds
      over three orders of magnitude with detection limits ranging from 6.6 to 0.064
      MUg/mL (S/N=3). The average recovery and RSD were within the range of 92.6-121.0
      and 1.0-12.0%, respectively. The proposed method has been used to detect the
      unconjugated aromatic acids simultaneously in urine samples with the advantages
      of obtaining more information about target analytes and avoiding redundant
      measurements and high assay cost, thus could find potential applications
      involving assays of biomarker compounds for the purpose of fast diagnose of some
      metabolic diseases including phenylketonuria.

PMID- 20680971
TI  - Robust linear mixed models using the skew t distribution with application to
      schizophrenia data.
AB  - We consider an extension of linear mixed models by assuming a multivariate skew t
      distribution for the random effects and a multivariate t distribution for the
      error terms. The proposed model provides flexibility in capturing the effects of
      skewness and heavy tails simultaneously among continuous longitudinal data. We
      present an efficient alternating expectation-conditional maximization (AECM)
      algorithm for the computation of maximum likelihood estimates of parameters on
      the basis of two convenient hierarchical formulations. The techniques for the
      prediction of random effects and intermittent missing values under this model are
      also investigated. Our methodologies are illustrated through an application to
      schizophrenia data.

PMID- 20680972
TI  - Laplace regression with censored data.
AB  - We consider a regression model where the error term is assumed to follow a type
      of asymmetric Laplace distribution. We explore its use in the estimation of
      conditional quantiles of a continuous outcome variable given a set of covariates
      in the presence of random censoring. Censoring may depend on covariates.
      Estimation of the regression coefficients is carried out by maximizing a non
      differentiable likelihood function. In the scenarios considered in a simulation
      study, the Laplace estimator showed correct coverage and shorter computation time
      than the alternative methods considered, some of which occasionally failed to
      converge. We illustrate the use of Laplace regression with an application to
      survival time in patients with small cell lung cancer.

PMID- 20680973
TI  - "Classification of therapy resistance based on longitudinal biomarker profiles"
      by M. Kohlmann, L. Held and V. P. Grunert.

PMID- 20680975
TI  - Thermal processes in red blood cells exposed to infrared laser tweezers (lambda =
      1064 nm).
AB  - Continuous-wave laser micro-beams are generally used as diagnostic tools in laser
      scanning microscopes or in the case of near-infrared (NIR) micro-beams, as
      optical traps for cell manipulation and force characterization. Because single
      beam traps are created with objectives of high numerical aperture, typical
      trapping intensities and photon flux densities are in the order of 10(6) W/cm(2)
      and 10(3) cm(-2) s(-1), respectively. The main idea of our theoretical study was
      to investigate the thermal reaction of RBCs irradiated by laser micro-beam. The
      study is supported by the fact that many experiments have been carried out with
      RBCs in laser NIR tweezers. In the present work it has been identified that the
      laser affects a RBC with a density of absorbed energy at approximately 10(7)
      J/cm(3), which causes a temperature rise in the cell of about 7-12  degrees C.

PMID- 20680974
TI  - Fiber-optic probes for in vivo depth-resolved neuron-activity mapping.
AB  - Specialty fiber probes are used for in vivo depth-resolved mapping of neuron
      activity through the optical detection of fluorescent-protein reporters expressed
      inside the living brain of anesthetized transgenic mice. Supercontinuum radiation
      produced by highly nonlinear photonic-crystal fibers is employed to demonstrate a
      simultaneous multicolor interrogation of several biomarkers in a model aqueous
      solution system, thus suggesting the way toward a multiplex mapping of various
      types of neuron dynamics inside the living brain.

PMID- 20680976
TI  - Clinical application of multiphoton tomography in combination with high-frequency
      ultrasound for evaluation of skin diseases.
AB  - The first-ever application of high-frequency ultrasound combined with multiphoton
      tomography (MPT) and dermoscopy in a clinical trial is reported. 47 patients with
      different dermatoses such as benign and malign skin cancers, connective tissue
      diseases, inflammatory skin diseases, and autoimmune bullous skin diseases have
      been investigated with (i) state-of-the-art and highly sophisticated ultrasound
      systems for dermatology, (ii) the femtosecond laser multiphoton tomograph and
      (iii) dermoscopes. Dermoscopy provides two-dimensional color images of the skin
      surface with a magnification up to 70 x. Depending on the ultrasonic frequencies
      from 7.5 MHz to 100 MHz, the signal depth varies from about 1 mm to 80 mm.
      Vertical ultrasound wide-field images provide fast information on depth and
      volume of the lesion. The 100 MHz ultrasound allows imaging with resolutions down
      to 16 MUm (axial) and 32 MUm (lateral). Multiphoton tomography provides 0.36 x
      0.36 x 0.001 mm3 horizontal optical sections of a particular region of interest
      with submicron resolution down to 200 MUm tissue depth. The autofluorescence of
      mitochondrial coenzymes, keratin, melanin, and elastin as well as the network of
      collagen structures can be imaged. The combination of ultrasound and MPT opens
      novel synergistic possibilities in diagnostics of skin diseases with a special
      focus on the early detection of skin cancer as well as the evaluation of
      treatments.

PMID- 20680977
TI  - Retrieving skin properties from in vivo spectral reflectance measurements.
AB  - A previously developed inverse method was applied to in vivo normal-hemispherical
      spectral reflectance measurements taken on the inner and outer forearm as well as
      the forehead of healthy white Caucasian and black African subjects. The inverse
      method was used to determine the thickness and melanin concentration in the
      epidermis, dermal blood volume fraction and oxygen saturation, and skin's
      spectral scattering coefficient. It was established that changes in melanin
      concentration due to racial difference and tanning, and differences in epidermal
      thickness and blood volume with anatomical location were detectable. The
      retrieved values were also consistent with independent measurements reported in
      the literature. The same method could be used for optical diagnosis of
      pathologies affecting the structure and pigmentation of human skin.

PMID- 20680978
TI  - Natural diversity to guide focused directed evolution.
AB  - Simultaneous multiple site-saturation mutagenesis was performed at four active
      site positions of an esterase from Pseudomonas fluorescens to improve its ability
      to convert 3-phenylbutyric acid esters (3-PBA) in an enantioselective manner.
      Based on an appropriate codon choice derived from a structural alignment of 1751
      sequences of alpha/beta-hydrolase fold enzymes, only those amino acids were
      considered for library creation that appeared frequently in structurally
      equivalent positions. Thus, the number of mutants to be screened could be
      substantially reduced while the number of functionally intact variants was
      increased. Whereas the wild-type esterase showed only marginal activity and poor
      enantioselectivity (E(true)=3.2) towards 3-PBA-ethyl ester, a significant number
      of hits with improved rates (up to 240-fold) and enantioselectivities (up to
      E(true)=80) were identified in these "smart" libraries.

PMID- 20680979
TI  - The biosynthesis of the aroma volatile 2-methyltetrahydrothiophen-3-one in the
      bacterium Chitinophaga Fx7914.
AB  - 2-Methyltetrahydrothiophen-3-one (3) is a volatile compound that plays an
      important role especially in food and flavour chemistry because it contributes to
      the aroma of several foodstuffs including wine. Although 3 can be formed by
      chemical reactions during food preparation, it is also produced by
      microorganisms. Recent studies with yeasts showed that methionine (1) is a
      potential precursor of 3, but the mechanism of the transformation is unknown. The
      biosynthetic pathway leading to 3 in the bacterium Chitinophaga Fx7914 was
      probed. Extensive feeding experiments with differently labelled precursors by
      using liquid cultures of Chitinophaga Fx7914 were performed. The volatiles
      released by the bacterium were collected by using a closed loop stripping
      apparatus (CLSA) and analysed by GC-MS. The observed incorporation pattern of the
      precursors into 3 led to the elucidation of the biosynthetic pathway. One part of
      the compound 2 originates from homocysteine (15), which is transformed into 3
      mercaptopropanal (17). The second biosynthetic building block is pyruvate (14).
      An acyloin-forming reaction furnishes the key intermediate 21, which cyclises
      intramolecularly to a diol. Dehydration followed by tautomerisation lead to the
      cyclic ketone 3, which is produced by the bacterium in racemic form.

PMID- 20680980
TI  - A Bayesian analysis of mixture structural equation models with non-ignorable
      missing responses and covariates.
AB  - In behavioral, biomedical, and social-psychological sciences, it is common to
      encounter latent variables and heterogeneous data. Mixture structural equation
      models (SEMs) are very useful methods to analyze these kinds of data. Moreover,
      the presence of missing data, including both missing responses and missing
      covariates, is an important issue in practical research. However, limited work
      has been done on the analysis of mixture SEMs with non-ignorable missing
      responses and covariates. The main objective of this paper is to develop a
      Bayesian approach for analyzing mixture SEMs with an unknown number of
      components, in which a multinomial logit model is introduced to assess the
      influence of some covariates on the component probability. Results of our
      simulation study show that the Bayesian estimates obtained by the proposed method
      are accurate, and the model selection procedure via a modified DIC is useful in
      identifying the correct number of components and in selecting an appropriate
      missing mechanism in the proposed mixture SEMs. A real data set related to a
      longitudinal study of polydrug use is employed to illustrate the methodology.

PMID- 20680981
TI  - Predicting treatment effects using biomarker data in a meta-analysis of clinical
      trials.
AB  - A biomarker (S) measured after randomization in a clinical trial can often
      provide information about the true endpoint (T) and hence the effect of treatment
      (Z). It can usually be measured earlier and more easily than T and as such may be
      useful to shorten the trial length. A potential use of S is to completely replace
      T as a surrogate endpoint to evaluate whether the treatment is effective. Another
      potential use of S is to serve as an auxiliary variable to help provide
      information and improve the inference on the treatment effect prediction when T
      is not completely observed. The objective of this report is to focus on its role
      as an auxiliary variable and to identify situations when S can be useful to
      increase efficiency in predicting the treatment effect in a new trial in a
      multiple-trial setting. Both S and T are continuous. We find that higher
      efficiency gain is associated with higher trial-level correlation but not
      individual-level correlation when only S, but not T is measured in a new trial;
      but, the amount of information recovery from S is usually negligible. However,
      when T is partially observed in the new trial and the individual-level
      correlation is relatively high, there is substantial efficiency gain by using S.
      For design purposes, our results suggest that it is often important to collect
      markers that have high adjusted individual-level correlation with T and at least
      a small amount of data on T. The results are illustrated using simulations and an
      example from a glaucoma clinical trial.

PMID- 20680982
TI  - Efforts to adjust for confounding by neighborhood using complex survey data.
AB  - In social epidemiology, one often considers neighborhood or contextual effects on
      health outcomes, in addition to effects of individual exposures. This paper is
      concerned with the estimation of an individual exposure effect in the presence of
      confounding by neighborhood effects, motivated by an analysis of National Health
      Interview Survey (NHIS) data. In the analysis, we operationalize neighborhood as
      the secondary sampling unit of the survey, which consists of small groups of
      neighboring census blocks. Thus the neighborhoods are sampled with unequal
      probabilities, as are individuals within neighborhoods. We develop and compare
      several approaches for the analysis of the effect of dichotomized individual
      level education on the receipt of adequate mammography screening. In the
      analysis, neighborhood effects are likely to confound the individual effects, due
      to such factors as differential availability of health services and differential
      neighborhood culture. The approaches can be grouped into three broad classes:
      ordinary logistic regression for survey data, with either no effect or a fixed
      effect for each cluster; conditional logistic regression extended for survey
      data; and generalized linear mixed model (GLMM) regression for survey data.
      Standard use of GLMMs with small clusters fails to adjust for confounding by
      cluster (e.g. neighborhood); this motivated us to develop an adaptation. We use
      theory, simulation, and analyses of the NHIS data to compare and contrast all of
      these methods. One conclusion is that all of the methods perform poorly when the
      sampling bias is strong; more research and new methods are clearly needed.

PMID- 20680983
TI  - A method for monitoring a process from an out of control to an in control state:
      Application to the learning curve.
AB  - The cumulative summation (CUSUM) test is increasingly being used in medicine to
      monitor a wide variety of processes such as cardiac surgery or disease outbreaks.
      The CUSUM sequentially tests the null hypothesis that the process is in control,
      i.e. its mean is equal to a given target. Thus, it detects when the process
      changes to an out of control state. Conversely, monitoring the learning curve
      requires detecting the time when the process reaches an in control state. In this
      work we develop an alternative to the CUSUM, the learning curve CUSUM (LC-CUSUM),
      that serves to detect when a process deviates from an out of control state to an
      in control state. The test is based on a two one-sided tests procedure where the
      null hypothesis is that the process is out of control. This can be written as
      H(0): |mu-mu(0)|> or =delta tested against H(1): |mu-mu(0)|< delta. The null
      hypothesis is thus the union of two one-sided hypotheses and is rejected when
      both are rejected. A CUSUM test statistic is then constructed for each hypothesis
      in a traditional way. The properties of the test are investigated through
      numerical simulations, and are illustrated on the learning curve of an
      endoscopist performing endoscopic retrograde cholangiopancreatographies for
      biliary tract disorders.

PMID- 20680984
TI  - A spatial scan statistic for multinomial data.
AB  - As a geographical cluster detection analysis tool, the spatial scan statistic has
      been developed for different types of data such as Bernoulli, Poisson, ordinal,
      exponential and normal. Another interesting data type is multinomial. For
      example, one may want to find clusters where the disease-type distribution is
      statistically significantly different from the rest of the study region when
      there are different types of disease. In this paper, we propose a spatial scan
      statistic for such data, which is useful for geographical cluster detection
      analysis for categorical data without any intrinsic order information. The
      proposed method is applied to meningitis data consisting of five different
      disease categories to identify areas with distinct disease-type patterns in two
      counties in the U.K. The performance of the method is evaluated through a
      simulation study.

PMID- 20680985
TI  - A binning method for analyzing mixed longitudinal data measured at distinct time
      points.
AB  - For longitudinal data where the response and time-dependent predictors within
      each individual are measured at distinct time points, traditional longitudinal
      models such as generalized linear mixed effects models or marginal models cannot
      be directly applied. Instead, some preprocessing such as smoothing is required to
      temporally align the response and predictors. We propose a binning method, which
      results in equally spaced bins of time. After incorporating binning, traditional
      models can be applied. The proposed binning approach was applied on a
      longitudinal hemodialysis study to look for possible contemporaneous and lagged
      effects between occurrences of a health event (i.e. infection) and levels of a
      protein marker of inflammation (i.e. C-reactive protein). Both Poisson mixed
      effects models and zero-inflated Poisson (ZIP) mixed effects models were applied
      to the subsequent data, and some important biological findings about
      contemporaneous and lagged associations were uncovered. In addition, a simulation
      study was conducted to investigate various properties of the binning approach.

PMID- 20680987
TI  - A flexible approach to the crossing hazards problem.
AB  - We propose a simple and flexible framework for the crossing hazards problem. The
      method is not confined to two-sample problems, but may also work with continuous
      exposure variables whose effect changes its sign at some time-point of the
      observed follow-up time. Penalized partial likelihood estimation relies upon the
      assumption of a smooth hazard ratio via low-rank basis splines with a
      conventional difference penalty to ensure smoothness, and additional ad hoc
      penalties to obtain restricted estimates useful in the context of crossing
      hazards. The framework naturally also leads to a statistical test that has good
      power for revealing a global effect under several alternatives, including
      crossing hazards. We provide the results from a real-data analysis and from some
      simulations to illustrate empirically the performance of the proposed approach as
      compared with the possible alternatives.

PMID- 20680986
TI  - Assessing agreement in the timing of treatment initiation determined by repeated
      measurements of novel versus gold standard technologies with application to the
      monitoring of CD4 counts in HIV-infected patients.
AB  - Repeated biomarker measurements are often taken over time to help assess risk of
      disease progression and guide clinical decision-making, such as whether to start
      treatment. Unfortunately, gold standard methodologies for measuring biomarkers
      are often prohibitively expensive or unavailable in resource-limited settings.
      For example, the costs of monitoring HIV-infected subjects to decide when to
      start or change treatments are a significant burden for many countries, often
      exceeding the costs of treatments. A major issue concerns how to evaluate changes
      in timing of key clinical decisions if a new, simpler or less expensive
      technology were used instead of the gold standard. We develop a framework for
      addressing this problem and apply it to the case of monitoring CD4 counts in HIV
      infected patients. We focus on the practically important situation in which
      longitudinal natural history data are available for the gold standard (flow
      cytometry for CD4 counts), but where the first data expected for a new technology
      will come from a cross-sectional method comparison study, allowing for estimation
      of variability and systematic differences (bias) between the two technologies. In
      a case study, we illustrate how a combination of statistical modeling and
      simulation study might be used to evaluate the potential impact of using a new
      technology on treatment starting times in a population of HIV-infected subjects.
      This gives developers of new CD4 measurement technologies insight into what might
      constitute acceptable increases in variability and/or bias for novel methods. We
      finish with a discussion of our findings and some statistical problems that need
      further work.

PMID- 20680988
TI  - Comment on 'Estimating average annual per cent change in trend analysis' by Clegg
      LX, Hankey BF, Tiwari R, Feuer EJ, Edwards BK, Statistics in Medicine 2009;
      28:3670-3682.
AB  - We discuss some issues relevant to paper of Clegg and co-authors published in
      Statistics in Medicine; 28, 3670-3682. Emphasis is on computation of the variance
      of the sum of products of two estimates, slopes and breakpoints.

PMID- 20680990
TI  - Investigating the links between neurocognitive functions and dyslexia. Editorial.

PMID- 20680992
TI  - Developmental dyslexia and explicit long-term memory.
AB  - The reduced verbal long-term memory capacities often reported in dyslexics are
      generally interpreted as a consequence of their deficit in phonological
      coding.The present study was aimed at evaluating whether the learning deficit
      exhibited by dyslexics was restricted only to the verbal component of the long
      term memory abilities or also involved visual-object and visual-spatial domain. A
      further goal of the present study was to investigate the predictive value of non
      verbal long-term memory abilities with respect to word and non-word reading in
      dyslexic children.In accordance with these aims, performances of 60 dyslexic
      children were compared with that of 65 age-matched normal readers on verbal,
      visual-spatial and visual-object task.Results documented a generalized impairment
      of episodic long-term memory capacities in dyslexic children and the results did
      not vary as a function of children's age.Furthermore, in addition to verbal
      measures, also individual differences in non-verbal long-term memory tasks turn
      out to be good predictors of reading difficulties in dyslexics.Our findings
      indicate that the long-term memory deficit in dyslexia is not limited to the
      dysfunction of phonological components but also involves visual-object and visual
      spatial aspect, thus suggesting that dyslexia is associated to multiple cognitive
      deficits.

PMID- 20680991
TI  - Procedural learning and dyslexia.
AB  - Three major 'neural systems', specialized for different types of information
      processing, are the sensory, declarative, and procedural systems. It has been
      proposed (Trends Neurosci., 30(4), 135-141) that dyslexia may be attributable to
      impaired function in the procedural system together with intact declarative
      function. We provide a brief overview of the increasing evidence relating to the
      hypothesis, noting that the framework involves two main claims: first that
      'neural systems' provides a productive level of description avoiding the
      underspecificity of cognitive descriptions and the overspecificity of brain
      structural accounts; and second that a distinctive feature of procedural learning
      is its extended time course, covering from minutes to months. In this article, we
      focus on the second claim. Three studies-speeded single word reading, long-term
      response learning, and overnight skill consolidation-are reviewed which together
      provide clear evidence of difficulties in procedural learning for individuals
      with dyslexia, even when the tasks are outside the literacy domain. The
      educational implications of the results are then discussed, and in particular the
      potential difficulties that impaired overnight procedural consolidation would
      entail. It is proposed that response to intervention could be better predicted if
      diagnostic tests on the different forms of learning were first undertaken.

PMID- 20680993
TI  - Visual spatial attention and speech segmentation are both impaired in
      preschoolers at familial risk for developmental dyslexia.
AB  - Phonological skills are foundational of reading acquisition and impaired
      phonological processing is widely assumed to characterize dyslexic individuals.
      However, reading by phonological decoding also requires rapid selection of
      sublexical orthographic units through serial attentional orienting, and recent
      studies have shown that visual spatial attention is impaired in dyslexic
      children. Our study investigated these different neurocognitive dysfunctions,
      before reading acquisition, in a sample of preschoolers including children with
      (N=20) and without (N=67) familial risk for developmental dyslexia. Children were
      tested on phonological skills, rapid automatized naming, and visual spatial
      attention. At-risk children presented deficits in both visual spatial attention
      and syllabic segmentation at the group level. Moreover, the combination of visual
      spatial attention and syllabic segmentation scores was more reliable than either
      single measure for the identification of at-risk children. These findings suggest
      that both visuo-attentional and perisylvian-auditory dysfunctions might adversely
      affect reading acquisition, and may offer a new approach for early identification
      and remediation of developmental dyslexia.

PMID- 20680994
TI  - On the importance of anchoring and the consequences of its impairment in
      dyslexia.
AB  - One of the main impediments of individuals with reading difficulties and
      individuals with language difficulties is poor working memory. Typically measured
      using verbal stimuli, working memory deficits have often been considered as one
      aspect of the phonological difficulty putatively underlying dyslexia. Over the
      years it has been shown that a broad range of auditory discrimination abilities
      are also mildly impaired. Here we present evidence that a domain general, rather
      than a phonology specific, deficits in the ability to implicitly use contextual
      information, which we term anchoring, can account for both types of deficits. We
      propose that anchoring ability, which reflects a basic biological mechanism for
      replacing effortful mechanisms of explicit working memory with automatic
      mechanisms of implicit memory, and consequently boost performance in both
      perceptual and cognitive tasks, is a crucial factor in our ability to be expert
      users of oral and written language.

PMID- 20680995
TI  - Interaction of phonological awareness and 'magnocellular' processing during
      normal and dyslexic reading: behavioural and fMRI investigations.
AB  - We investigated whether phonological deficits are a consequence of magnocellular
      processing deficits in dyslexic and control children. In Experiment 1, children
      were tested for reading ability, phonological awareness, visuo-magnocellular
      motion perception, and attention shifting (sometimes considered as magnocellular
      function). A two-step cluster analysis of the behavioural scores revealed four
      clusters of children. Phonological awareness was correlated with attention
      (cluster musical sharp1) or motion detection (cluster musical sharp2), whereas
      attention and motion detection were correlated in cluster musical sharp3. In
      cluster musical sharp4, all variables were uncorrelated. In Experiment 2, the
      same variables plus auditory discrimination were tested with fMRI in a sub-sample
      of Experiment 1. Although dyslexics had reduced activation in visual or auditory
      cortex during motion detection or auditory discrimination, respectively, they had
      increased right frontal activation in areas 44 and 45 in all 'magnocellular'
      (including auditory) tasks. In contrasts, during phonological decisions, there
      was higher activation for good readers than dyslexics in left areas 44 and 45.
      Together, the two experiments give insight into the interplay of phonological and
      magnocellular processing during reading. Distinct left versus right frontal
      effects reveal partly different underlying neural mechanisms. These data
      contradict the view that phonological processing deficits in dyslexia necessarily
      result from impaired magnocellular functioning.

PMID- 20680998
TI  - International regulatory activity restricting COX-2 inhibitor use and deaths due
      to gastrointestinal haemorrhage and myocardial infarction.
AB  - PURPOSE: To investigate trends in mortality rates due to both myocardial
      infarction and gastrointestinal haemorrhage before and after rofecoxib withdrawal
      and the release of regulatory guidance regarding the use of other COX-2
      inhibitors. METHODS: International ecological study of temporal trends in deaths
      from myocardial infarction and gastrointestinal haemorrhage around 2004 when
      regulatory activity restricted the use of COX-2 inhibitors. Mortality data in
      countries with low child and adult male mortality (WHO mortality stratum A) were
      analysed. RESULTS: Comparing, on a country-by-country basis, post-2004 mortality
      rates with those expected from a continuation of preceding trends, there was no
      evidence of a deviation from the earlier trends in mortality from
      gastrointestinal haemorrhage or acute myocardial infarction in 50-69 year olds.
      Amongst 70+ year olds however, there was evidence of lower gastrointestinal
      haemorrhage mortality (rate ratio 0.963, 95% confidence interval 0.948 to 0.977)
      and of lower acute myocardial infarction mortality (rate ratio 0.981, 95%
      confidence interval 0.977 to 0.986) after 2004. These associations were similar
      for males and females. CONCLUSIONS: We did not find evidence of an increase in
      mortality due to gastrointestinal haemorrhage following the withdrawal of
      rofecoxib in 2004, and coincident concern amongst regulatory bodies about other
      COX-2 inhibitors. In fact in men and women aged 70 years or older there appeared
      to be reduced mortality due to gastrointestinal haemorrhage and acute myocardial
      infarction compared to what was expected from mortality trends before 2004.

PMID- 20680999
TI  - Does folic acid use decrease the risk for spina bifida after in utero exposure to
      valproic acid?
AB  - PURPOSE: Women with child wish are advised to take folic acid supplements to
      reduce the risk for spina bifida. However, there is less evidence for this
      protective effect in women using valproic acid (VPA). We investigated the effect
      of folic acid in women exposed to VPA in the first trimester of pregnancy.
      METHODS: A case-control study was performed with data from a population-based
      registry of congenital malformations. Our cases were spina bifida registrations
      and all other malformed registrations (excluding folic acid sensitive
      malformations) were used as controls. RESULTS: The ORs for the effect of correct
      folic acid use were calculated among antiepileptic drug (AED) unexposed
      pregnancies 0.5 [95%CI: 0.3-0.7] and among VPA exposed pregnancies 1.0 [95%CI:
      0.1-7.6]. DISCUSSION: Due to power-reasons, we cannot conclude that folic acid
      has no effect on the risk for spina bifida among VPA exposed pregnancies.
      Although for AED unexposed pregnancies we found a decreased risk. Results from
      (animal) studies support a biologically plausible association between VPA, folic
      acid and spina bifida. While folic acid might not be able to reduce the risk for
      lower spina bifida lesions caused by VPA, the use of folic acid might be
      important to reduce the risk for higher, folic acid sensitive spina bifida
      lesions. Further research is needed to get more insight in the most effective
      form and dose of FA in women that use VPA to reduce the risk for (higher forms
      of) spina bifida.

PMID- 20681000
TI  - Using medical records to supplement a claims-based comparative effectiveness
      analysis of antidepressants.
AB  - PURPOSE: Because health insurance claims lack clinical information, comparative
      effectiveness research studies that rely on these data may be challenging to
      interpret and may result in biased inference. We conducted an exploratory study
      to determine if medical information contained in patient charts could offer
      clinical details that would assist in interpreting the results of a claims-based
      comparative effectiveness study of selective serotonin reuptake inhibitors
      (SSRIs). METHODS: Retrospective review of 457 charts of patients initiating SSRI
      treatment. Descriptive data elements included patient diagnosis, symptoms of
      depressive and anxiety disorders, provider's assessment, and medication treatment
      and side effects. RESULTS: Most subjects were excluded from the study because
      their charts were not accessible (58.7%), they did not have a follow-up visit
      (55.6%), providers could not be contacted (58.0%), or providers refused
      participation in the study (36.5%). Among those included in the study, most
      patients were noted to have depression, but most charts lacked information on the
      majority of depression symptoms at baseline and follow-up. Few concomitant
      symptoms, side effects, and other important clinical and treatment
      characteristics were recorded. CONCLUSIONS: Inability to obtain charts due to
      plan or provider refusal, lack of available information in charts at key times in
      the course of illness, and missing data elements posed considerable challenges
      and prevented firm conclusions beyond those drawn from the parent, claims-based
      study.

PMID- 20681001
TI  - Comparison of potential risk factors for medication errors with and without
      patient harm.
AB  - PURPOSE: To compare determinants for medication errors leading to patient harm
      with determinants for medication errors without patient harm. METHODS: A two-way
      case-control design was used to identify determinants for medication errors
      without harm (substudy 1) and determinants for medication errors causing harm
      (substudy 2). Data of patients admitted to five internal medicine wards of two
      Dutch hospitals during 5 months were collected prospectively by chart review.
      Medication errors were detected and classified by two pharmacists. Consensus
      between five pharmacists was reached on the causal relationship between
      medication errors and patient harm. Data analysis was performed by multivariate
      logistic regression. RESULTS: We included 7286 medication orders, of which 3315
      without errors (controls), and 5622 medication errors without harm (cases
      substudy 1) and 102 medication errors causing harm (cases substudy 2) were
      identified. Hospital, ward and the therapeutic class anti-infectives were
      associated with both medication errors without harm (hospital odds ratio (OR)
      1.40; 95% confidence interval (CI) 1.21-1.63), TweeSteden hospital (TSh)
      geriatrics OR 2.03; 95% CI 1.73-2.38, TSh general internal medicine OR 1.44; 95%
      CI 1.23-1.69 and anti-infectives OR 1.28; 95% CI 1.06-1.56) and medication errors
      with harm (hospital OR 4.91; 95% CI 3.02-7.79, TSh geriatrics OR 5.76; 95% CI
      2.52-13.15, TSh general internal medicine OR 6.51; 95% CI 2.82-15.02 and anti
      infectives OR 4.20; 95% CI 2.24-7.90). CONCLUSIONS: This study shows that
      organisational determinants (hospital, ward) are comparable for medication errors
      with and without harm. For conclusions on patient- and medication-related
      determinants studies with larger sample sizes are needed.

PMID- 20681004
TI  - Extent of pharmacovigilance among resident doctors in Edo and Lagos states of
      Nigeria: important issues unaddressed by the authors.

PMID- 20681003
TI  - A basic study design for expedited safety signal evaluation based on electronic
      healthcare data.
AB  - Active drug safety monitoring based on longitudinal electronic healthcare
      databases (a Sentinel System), as outlined in recent FDA-commissioned reports,
      consists of several interlocked processes, including signal generation, signal
      strengthening, and signal evaluation. Once a signal of a potential drug safety
      issue is generated, signal strengthening and signal evaluation have to follow in
      short sequence in order to quickly provide as much information about the
      triggering drug-event association as possible. This paper proposes a basic study
      design based on the incident user cohort design for expedited signal evaluation
      in longitudinal healthcare databases. It will not resolve all methodological
      issues nor will it fit all study questions arising within the framework of a
      Sentinel System. It should rather be seen as a guidance that will fit the
      majority of situations and serve as a starting point for adaptations to specific
      studies. Such an approach will expedite and structure the process of study
      development and highlight specific assumptions, which is particularly valuable in
      a Sentinel System where signals are by definition preliminary and evaluation of
      signals is time critical.

PMID- 20681002
TI  - Racial and ethnic disparities in cardiovascular medication use among older adults
      in the United States.
AB  - BACKGROUND: Despite persistent racial/ethnic disparities in cardiovascular
      disease (CVD) among older adults, information on whether there are similar
      disparities in the use of prescription and over-the-counter medications to
      prevent such disease is limited. We examined racial and ethnic disparities in the
      use of statins and aspirin among older adults at low, moderate, and high risk for
      CVD. METHODS AND RESULTS: In-home interviews, including a medication inventory,
      were administered between June 2005 and March 2006 to 3005 community-residing
      individuals, ages 57-85 years, drawn from a cross-sectional, nationally
      representative probability sample of the United States. Based on a modified
      version of the Adult Treatment Panel III (ATP III) risk stratification
      guidelines, 1066 respondents were at high cardiovascular risk, 977 were at
      moderate risk, and 812 were at low risk. Rates of use were highest among
      respondents at high cardiovascular risk. Racial differences were highest among
      respondents at high risk with blacks less likely than whites to use statins (38%
      vs. 50%, p = 0.007) and aspirin (29% vs. 44%, p = 0.008). After controlling for
      age, gender, comorbidity, and socioeconomic, and access to care factors,
      racial/ethnic disparities persisted. In particular, blacks at highest risk were
      less likely than their white counterparts to use statins (odds ratio (OR) 0.65,
      confidence interval (CI) 0.46-0.90) or aspirin (OR 0.61, CI 0.37-0.98).
      CONCLUSIONS: These results, based on an in-home survey of actual medication use,
      suggest widespread underuse of indicated preventive therapies among older adults
      at high cardiovascular risk in the United States. Racial/ethnic disparities in
      such use may contribute to documented disparities in cardiovascular outcomes.

PMID- 20681005
TI  - Ultrasound and the risk of nosocomial cross infection.

PMID- 20681006
TI  - Value of transvaginal sonography in assessing severe pelvic endometriosis.

PMID- 20681007
TI  - Design, synthesis and acaricidal activity of novel strobilurin derivatives
      containing pyrimidine moieties.
AB  - BACKGROUND: The intermediate derivatisation method based on bioisosteric
      replacement led to the discovery of the lead strobilurin compound 5a. To produce
      new strobilurin analogues with improved activity, a series of substituted
      pyrimidines were synthesised and bioassayed. RESULTS: The compounds were
      identified by (1)H NMR, IR, MS and elemental analysis. The highly active compound
      5 g was studied by X-ray diffraction. Preliminary bioassays demonstrated that
      some of the title compounds exhibited excellent acaricidal activity against
      Tetranychus cinnabarinus (Boisd.) at 10 mg L(-1). The relationship between
      structure and acaricidal activity is reported. CONCLUSION: The present work
      demonstrates that strobilurin derivatives containing pyrimidine moieties can be
      used as possible lead compounds for developing novel acaricides.

PMID- 20681008
TI  - Fusarium mycotoxins in various barley cultivars and their transfer into malt.
AB  - BACKGROUND: Fusarium toxins, secondary metabolites of toxinogenic Fusarium
      species, are found in a range of cereal grains. In this study the occurrence of
      the most commonest Fusarium toxins, namely nivalenol (NIV), deoxynivalenol (DON),
      deoxynivalenol-3-glucoside, fusarenon-X, 3- and 15-acetyldeoxynivalenol, HT-2 and
      T-2 toxins and zearalenone, in various barley cultivars harvested in 2005-2008
      was monitored. The impact of weather, locality, fungicide treatment and barley
      cultivar (hulless or covered) on contamination was evaluated. The transfer of
      these mycotoxins into malt was assessed. RESULTS: The most prevalent toxin was
      DON, which was found in 83% of samples (maximum level 180 ug kg(-1)), while HT-2
      was detected in 62% of samples (maximum level 716 ug kg(-1)). Using analysis of
      covariance, weather was found to be the key factor in all years (P < 0.001). A
      relationship between cultivar and contamination was confirmed only for HT-2 (P <
      0.001) and T-2 (P = 0.037), with higher levels of these toxins being observed in
      hulless cultivars. With the exception of NIV (P = 0.008), no significant
      relationship was found between fungicide treatment and contamination. No distinct
      trend regarding DON levels in malt was found, with both decreases and increases
      occurring. CONCLUSION: The results show an inter-annual variation in mycotoxin
      occurrence in barley cultivars as well as differences in contamination of malt
      produced from fungicide-treated and untreated barley.

PMID- 20681009
TI  - Current and emerging concepts in tumour metastasis.
AB  - Disseminated cancer accounts for most deaths due to malignancy. Despite this,
      research has focused predominantly on tumour development and progression at the
      primary site. Recently, attention has shifted towards the field of tumour
      metastasis. Several new and exciting concepts that have emerged in the past few
      years may shed light on this complex area. The established canonical theory of
      tumour metastasis, as a process emerging from a stepwise accumulation of genetic
      events fuelled by clonal evolution, has been challenged. New evidence suggests
      that malignant cells can disseminate at a much earlier stage than previously
      recognized in tumourigenesis. These findings have direct relevance to clinical
      practice and shed new light on tumour biology. Gene-profiling studies support
      this theory, suggesting that metastatic ability may be an innate property shared
      by the bulk of cells present early in a developing tumour mass. There is a
      growing recognition of the importance of host factors outside the primary site in
      the development of metastatic disease. The role of the 'pre-metastatic niche' is
      being defined and with this comes a new understanding of the function of bone
      marrow-derived progenitor cells in directing the dissemination of malignant cells
      to distant sites. Current research has highlighted the crucial roles played by
      non-neoplastic host cells within the tumour microenvironment in regulating
      metastasis. These new concepts have wide-ranging implications for our overall
      understanding of tumour metastasis and for the development of cancer
      therapeutics.

PMID- 20681010
TI  - Recycling and LFA-1-dependent trafficking of ICAM-1 to the immunological synapse.
AB  - Little is known about how adhesion molecules on APCs accumulate at immunological
      synapses. We show here that ICAM-1 on APCs is continuously internalized and
      rapidly recycled back to the interface after antigen-priming T-cell contact. The
      internalization rate is high in APCs, including Raji B cells and dendritic cells,
      but low in endothelial cells. Internalization is significantly reduced by
      inhibitors of Na(+)/H(+) exchangers (NHEs), suggesting that members of the NHE
      family regulate this process. Once internalized, ICAM-1 is co-localized with MHC
      class II in the polarized recycling compartment. Surprisingly, not only ICAM-1,
      but also MHC class II, is targeted to the immunological synapse through LFA-1
      dependent adhesion. Cytosolic ICAM-1 is highly mobile and forms a tubular
      structure. Inhibitors of microtubule or actin polymerization can reduce ICAM-1
      mobility, and thereby block accumulation at immunological synapses. Membrane ICAM
      1 also moves to the T-cell contact zone, presumably through an active,
      cytoskeleton-dependent mechanism. Collectively, these results demonstrate that
      ICAM-1 can be transported to the immunological synapse through the recycling
      compartment. Furthermore, the high-affinity state of LFA-1 on T cells is critical
      to induce targeted movements of both ICAM-1 and MHC class II to the immunological
      synapse on APCs.

PMID- 20681012
TI  - The impact of socioeconomic status on stage of cancer at diagnosis and survival:
      a population-based study in Ontario, Canada.
AB  - BACKGROUND: Lower socioeconomic status (SES) is associated with worsened cancer
      survival. The authors evaluate the impact of SES on stage of cancer at diagnosis
      and survival in Ontario, Canada. METHODS: All incident cases of breast, colon,
      rectal, nonsmall cell lung, cervical, and laryngeal cancer diagnosed in Ontario
      during the years 2003-2007 were identified by using the Ontario Cancer Registry.
      Stage information is captured routinely for patients seen at Ontario's 8 Regional
      Cancer Centers (RCCs). The Ontario population was divided into quintiles (Q1-Q5)
      based on community median household income reported in the 2001 census; Q1
      represents the poorest communities. Overall survival (OS) and cancer-specific
      survival (CSS) were determined with Kaplan-Meier methodology. A Cox model was
      used to evaluate the association between survival and SES, stage, and age.
      RESULTS: Stage at diagnosis was available for 38,431 of 44,802 (85%) of cases
      seen at RCCs. The authors observed only very small differences in stage
      distribution by SES. Across all cases in Ontario, the authors found substantial
      gradients in 5-year OS and 3-year CSS across Q1 and Q5 for breast (7% absolute
      difference in OS, P < .001; 4% CSS, P < .001), colon (8% OS, P < .001; 3% CSS, P
      = .002), rectal (9% OS, P < .001; 4% CSS, P = .096), nonsmall cell lung (3% OS, P
      = .002; 2% CSS, P = .317), cervical (16% OS, P < .001; 10% CSS, P = .118), and
      laryngeal cancers (1% OS, P = .045; 3% CSS, P = .011). Adjustments for stage and
      age slightly diminished the survival gradient only among patients with breast
      cancer. CONCLUSIONS: Despite universal healthcare, SES remains associated with
      survival among patients with cancer in Ontario, Canada. Disparities in outcome
      were not explained by differences in stage of cancer at time of diagnosis.

PMID- 20681011
TI  - Meat and components of meat and the risk of bladder cancer in the NIH-AARP Diet
      and Health Study.
AB  - BACKGROUND: Meat could be involved in bladder carcinogenesis via multiple
      potentially carcinogenic meat-related compounds related to cooking and
      processing, including nitrate, nitrite, heterocyclic amines (HCAs), and
      polycyclic aromatic hydrocarbons (PAHs). The authors comprehensively investigated
      the association between meat and meat components and bladder cancer. METHODS:
      During 7 years of follow-up, 854 transitional cell bladder-cancer cases were
      identified among 300,933 men and women who had completed a validated food
      frequency questionnaire in the large prospective NIH-AARP Diet and Health Study.
      The authors estimated intake of nitrate and nitrite from processed meat and HCAs
      and PAHs from cooked meat by using quantitative databases of measured values.
      Total dietary nitrate and nitrite were calculated based on literature values.
      RESULTS: The hazard ratios (HR) and 95% confidence intervals (CI) for red meat
      (HR for fifth quintile compared with first quintile, 1.22; 95% CI, 0.96-1.54;
      P(trend) = .07) and the HCA 2-amino-1 methyl-6-phenylimidazo(4,5-b)pyridine
      (PhIP) (HR, 1.19; 95% CI, 0.95-1.48; P(trend) = .06) conferred a borderline
      statistically significant increased risk of bladder cancer. Positive associations
      were observed in the top quintile for total dietary nitrite (HR, 1.28; 95% CI,
      1.02-1.61; P(trend) = .06) and nitrate plus nitrite intake from processed meat
      (HR, 1.29; 95% CI, 1.00-1.67; P(trend) = .11). CONCLUSIONS: These findings
      provided modest support for an increased risk of bladder cancer with total
      dietary nitrite and nitrate plus nitrite from processed meat. Results also
      suggested a positive association between red meat and PhIP and bladder
      carcinogenesis.

PMID- 20681013
TI  - Hemispheric asymmetries of motor versus nonmotor processes during (visuo)motor
      control.
AB  - Language and certain aspects of motor control are typically served by the left
      hemisphere, whereas visuospatial and attentional control are lateralized to the
      right. Here a (visuo)motor tracing task was used to identify hemispheric
      lateralization beyond the general, contralateral organization of the motor
      system. Functional magnetic resonance imaging (fMRI) was applied in 40 male right
      handers (19-30 yrs) during line tracing with dominant and nondominant hand, with
      and without visual guidance. Results revealed a network of areas activating more
      in the right than left hemisphere, irrespective of the effector. Inferior
      portions of frontal gyrus and parietal lobe overlapped largely with a previously
      described ventral attention network responding to unexpected or behaviourally
      relevant stimuli. This demonstrates a hitherto unreported functionality of this
      circuit that also seems to activate when spatial information is continuously
      exploited to adapt motor behaviour. Second, activation of left dorsal premotor
      and postcentral regions during tracing with the nondominant left hand was more
      pronounced than that in their right hemisphere homologues during tracing with the
      dominant right hand. These activation asymmetries of motor areas ipsilateral to
      the moving hand could not be explained by asymmetries in skill performance, the
      degree of handedness, or interhemispheric interactions. The latter was measured
      by a double-pulse transcranial magnetic stimulation paradigm, whereby a
      conditioning stimulus was applied over one hemisphere and a test stimulus over
      the other. We propose that the left premotor areas contain action representations
      strongly related to movement implementation which are also accessed during
      movements performed with the left body side.

PMID- 20681014
TI  - Two distinct neural networks support the mapping of meaning to a novel word.
AB  - Children can learn the meaning of a new word from context during normal reading
      or listening, without any explicit instruction. It is unclear how such meaning
      acquisition is supported and achieved in human brain. In this functional magnetic
      resonance imaging (fMRI) study we investigated neural networks supporting word
      learning with a functional connectivity approach. Participants were exposed to a
      new word presented in two successive sentences and needed to derive the meaning
      of the new word. We observed two neural networks involved in mapping the meaning
      to the new word. One network connected the left inferior frontal gyrus (LIFG)
      with the middle frontal gyrus (MFG), medial superior frontal gyrus, caudate
      nucleus, thalamus, and inferior parietal lobule. The other network connected the
      left middle temporal gyrus (LMTG) with the MFG, anterior and posterior cingulate
      cortex. The LIFG network showed stronger interregional interactions for new than
      real words, whereas the LMTG network showed similar connectivity patterns for new
      and real words. We proposed that these two networks support different functions
      during word learning. The LIFG network appears to select the most appropriate
      meaning from competing candidates and to map the selected meaning onto the new
      word. The LMTG network may be recruited to integrate the word into sentential
      context, regardless of whether the word is real or new. The LIFG and the LMTG
      networks share a common node, the MFG, suggesting that these two networks
      communicate in working memory.

PMID- 20681015
TI  - Strain-gated piezotronic logic nanodevices.

PMID- 20681016
TI  - Redox active mesoporous hybrid materials by in situ syntheses with urea-linked
      triethoxysilylated phenothiazines.
AB  - Triethoxysilyl functionalized phenothiazinyl ureas were synthesized and
      immobilized by in situ synthesis into mesoporous hybrid materials. The designed
      precursor molecules influence the structure of the final materials and the
      intermolecular distance of the phenothiazines. XRD and N(2) adsorption
      measurements indicate the presence of highly ordered two-dimensional hexagonally
      structured functional materials, while the incorporation of the organic compounds
      in the solid materials was proved by means of (13)C and (29)Si solid state NMR
      spectroscopy as well as by FT-IR spectroscopy. Upon oxidation with (NO)BF(4) or
      SbCl(5), stable phenothiazine radical cations were generated in the pores of the
      materials, which was detected by means of UV/Vis, emission, and EPR
      spectroscopies.

PMID- 20681017
TI  - The electrochemical response of graphene sheets is independent of the number of
      layers from a single graphene sheet to multilayer stacked graphene platelets.

PMID- 20681018
TI  - The retinoid signaling pathway inhibits hematopoiesis and uncouples from the Hox
      genes during hematopoietic development.
AB  - Retinoic acid (RA) is a well-established inducer of Hox genes during development
      of neurectoderm, however effects of RA on Hox expression are poorly defined in
      mesoderm and not defined in the hematopoietic compartment. Both Hox genes and
      retinoid signaling have been suggested to modulate hematopoietic stem cell (HSC)
      self-renewal, supporting the notion that RA signaling might drive HSC self
      renewal through Hox gene induction. Here, we investigate this possibility by
      comprehensively evaluating Hox gene expression using mouse embryonic stem cells
      differentiated in vitro. In unspecified mesoderm, we find that RA coordinately
      upregulates anterior 3' Hox genes from clusters A, B, and C, and downregulates
      posterior 5' Hox genes from clusters A-D. However, hematopoietic development of
      mesoderm was inhibited by RA, and we find further that retinoids are entirely
      dispensable for hematopoiesis in vitro. More surprisingly, in fully specified
      hematopoietic progenitors, Hox genes are refractory to regulation by RA, although
      other RA targets are normally regulated. Pulses of RA exposure demonstrate that
      the Hox complexes are decoupled from RA regulation progressively in lateral plate
      mesoderm as it undergoes hematopoietic specification. Thus, Hox genes are targets
      of the RA pathway only in selected cell types, and are clearly not regulated by
      RA in the earliest hematopoietic progenitors. We propose that the developmental
      uncoupling of the Hox complexes protects the Hox code from potential RA signaling
      centers as HSCs migrate or circulate during development.

PMID- 20681019
TI  - Fibroblast growth factor type 2 signaling is critical for DNA repair in human
      keratinocyte stem cells.
AB  - Tissue stem cells must be endowed with superior maintenance and repair systems to
      ensure genomic stability over multiple generations, which would be less necessary
      in more differentiated cells. We previously reported that human keratinocyte stem
      cells were more resistant to ionizing radiation toxicity than their direct
      progeny, the keratinocyte progenitor cells. In the present study we addressed the
      mechanisms underlying this difference. Investigations of DNA repair showed that
      both single and double DNA strand breaks were repaired more rapidly and more
      efficiently in stem cells than in progenitors. As cell signaling is a key
      regulatory step in the management of DNA damage, a gene profiling study was
      performed. Data revealed that several genes of the fibroblast growth factor type
      2 (FGF2) signaling pathway were induced by DNA damage in stem cells and not in
      progenitors. Furthermore, an increased content of the FGF2 protein was found in
      irradiated stem cells, both for the secreted and the cellular forms of the
      protein. To examine the role of endogenous FGF2 in DNA repair, stem cells were
      exposed to FGF2 pathway inhibitors. Blocking the FGF2 receptor (FGF receptor 1)
      or the kinase (Ras-mitogen-activated protein kinase 1) resulted in a inhibition
      of single and double DNA strand-break repair in the keratinocyte stem cells.
      Moreover, supplementing the progenitor cells with exogenous FGF2 activated their
      DNA repair. We propose that, apart from its well-known role as a strong mitogen
      and prosurvival factor, FGF2 helps to maintain genomic integrity in stem cells by
      activating stress-induced DNA repair.

PMID- 20681021
TI  - Metal-based nanoparticles and their toxicity assessment.
AB  - Nanoparticles (NPs) can potentially cause adverse effects on organ, tissue,
      cellular, subcellular, and protein levels due to their unusual physicochemical
      properties (e.g., small size, high surface area to volume ratio, chemical
      composition, crystallinity, electronic properties, surface structure reactivity
      and functional groups, inorganic or organic coatings, solubility, shape, and
      aggregation behavior). Metal NPs, in particular, have received increasing
      interest due to their widespread medical, consumer, industrial, and military
      applications. However, as particle size decreases, some metal-based NPs are
      showing increased toxicity, even if the same material is relatively inert in its
      bulk form (e.g., Ag, Au, and Cu). NPs also interact with proteins and enzymes
      within mammalian cells and they can interfere with the antioxidant defense
      mechanism leading to reactive oxygen species generation, the initiation of an
      inflammatory response and perturbation and destruction of the mitochondria
      causing apoptosis or necrosis. As a result, there are many challenges to overcome
      before we can determine if the benefits outweigh the risks associated with NPs.

PMID- 20681020
TI  - Characterization of midgut stem cell- and enteroblast-specific Gal4 lines in
      drosophila.
AB  - The homeostasis of Drosophila midgut is maintained by multipotent intestinal stem
      cells (ISCs), each of which gives rise to a new ISC and an immature daughter
      cell, enteroblast (EB), after one asymmetric cell division. In Drosophila, the
      Gal4-UAS system is widely used to manipulate gene expression in a tissue- or cell
      specific manner, but in Drosophila midgut, there are no ISC- or EB-specific Gal4
      lines available. Here we report the generation and characterization of Dl-Gal4
      and Su(H)GBE-Gal4 lines, which are expressed specifically in the ISCs and EBs
      separately. Additionally, we demonstrate that Dl-Gal4 and Su(H)GBE-Gal4 are
      expressed in adult midgut progenitors (AMPs) and niche peripheral cells (PCs)
      separately in larval midgut. These two Gal4 lines will serve as invaluable tools
      for navigating ISC behaviors.

PMID- 20681022
TI  - Notch as a molecular switch in neural stem cells.

PMID- 20681023
TI  - Molecular mechanisms of viral infection and propagation: an overview of the
      second Advanced Summer School in Africa.

PMID- 20681024
TI  - Multiple roles of cytochrome c oxidase in mammalian cells under action of red and
      IR-A radiation.
AB  - This article reviews the current knowledge in photobiology and photomedicine
      about the influence of monochromatic, quasimonochromatic, and bread-band
      radiation of red-to-near infrared (IR-A) part on solar spectrum upon mammalian
      cells and human skin. The role of cytochrome c oxidase as the photoacceptor and
      photosignal transducer is underlined and its photosensitivity at certain
      circumstances is discussed. The role of ATP as a critical signaling molecule is
      discussed.

PMID- 20681026
TI  - Notch as a molecular switch in neural stem cells.
AB  - Notch signaling pathway, originally discovered in Drosophila, impinges on a wide
      array of cellular processes including cell proliferation, cell differentiation,
      and cell apoptosis. Recent accumulating evidences implicated the important roles
      of Notch signal pathway in different aspects of stem cell biology of neural stem
      cell (NSC). In vivo and in vitro studies illustrated that Notch signal pathway
      could promote gliogenesis, inhibit premature neurogenesis, and be involved in
      self-renew of NSC. This short review summarizes the roles of the Notch signaling
      pathway on gliogenesis, neurogenesis, and self-renew of NSC and their underlying
      molecular mechanisms.

PMID- 20681025
TI  - The multifaceted effects of granulocyte colony-stimulating factor in
      immunomodulation and potential roles in intestinal immune homeostasis.
AB  - The three colony-stimulating factors, granulocyte/macrophage colony-stimulating
      factor (GM-CSF), macrophage colony-stimulating factor (M-CSF), and granulocyte
      colony-stimulating factor (G-CSF), have been regarded as immunostimulators
      because of their role in granulocyte and myeloid hematopoiesis and immune
      function. However, unlike GM-CSF and M-CSF, G-CSF possesses immunosuppressive
      effects on other immune cells including monocytes/macrophages, dendritic cells,
      and T lymphocytes when exogenously administered. Given the immunomodulatory
      effects of exogenous G-CSF, endogenous G-CSF may also play an important role in
      maintaining local immune homeostasis in tissue in which it is highly and
      constitutively produced. This review highlights the potential role of G-CSF in
      immunomodulation and intestinal immune homeostasis.

PMID- 20681027
TI  - Hypoxia regulates the ferrous iron uptake and reactive oxygen species level via
      divalent metal transporter 1 (DMT1) Exon1B by hypoxia-inducible factor-1.
AB  - Hypoxia has been shown to increase the expression of a variety of proteins
      involved in iron homeostasis, including ceruloplasmin, transferrin, and
      transferring receptor. Divalent metal transporter 1 (DMT1) is a transmembrane
      protein that is important in divalent metal ion transport, in particular iron.
      Although previous studies have provided that DMT1 exon1A is regulated by hypoxia,
      little is known about the relationship between DMT1 exon1B and hypoxia. Hypoxia
      inducible factor 1 (HIF-1) is a transcription factor which is stabilized when
      mammalian cells are subjected to hypoxia. In this study, we have identified a
      functional hypoxia-response element (HRE) at position of -327 to -323 (-ACGTG-)
      in DMT1 exon1B promoter using a combination of bioinformatics and biological
      approaches. Both the total cellular iron and ferrous uptake increased after
      hypoxia, decreased after DMT1 RNA interference. Reactive oxygen species (ROS)
      were also changed by +iron responsive element (IRE) DMT1 exon1B overexpression.
      These findings implicated DMT1 exon1B was a target gene for HIF-1. Hypoxia might
      affect cellular iron uptake through regulating the expression of DMT1. When iron
      was present in excess, cells might be damaged by the ROS production.

PMID- 20681028
TI  - The glycemic response is a personal attribute.
AB  - The Glycemic Index (GI) is a measure of the extent of the change in blood glucose
      content (glycemic response) following consumption of digestible carbohydrate,
      relative to a standard such as glucose. We have explored whether the reported GIs
      of foods are a sufficient guide to a person wishing to avoid large glycemic
      responses and thereby avoid hyperglycemia. For this purpose, volunteers carried
      out multiple tests of four foods, following overnight fasting, measuring the
      glycemic response over 2 H. The areas under the blood glucose/time curves (AUCs)
      were compared. Each food tester displayed individual, characteristic glycemic
      responses to each food, unrelated to any other tester's response. Wide variations
      (up to 5-fold) were seen between the average AUCs for the same test by different
      testers. The absolute magnitudes of the glycemic responses are important for
      individuals trying to control blood sugar and/or body weight, but using published
      GI lists as a guide to control the glycemic response is not fully informative.
      This is because in calculating the GI, individual glycemic responses to glucose
      are normalized to 100. GI values are, therefore, relative and are not necessarily
      a reliable guide to the person's actual individual AUC when consuming a food.
      Without knowledge of the person's characteristic blood glucose responses,
      reliance only on the GI may be misleading.

PMID- 20681029
TI  - Robert Kellogg Crane: a scientist remembers.

PMID- 20681030
TI  - Gene expression, glycocalyx assay, and surface properties of human endothelial
      cells cultured on hydrogel matrix with sulfonic moiety: Effect of elasticity of
      hydrogel.
AB  - We measured the gene expression, glycocalyx content, and surface properties of
      human coronary artery endothelial cells (HCAECs) cultured on poly(sodium p
      styrene sulfonate) (PNaSS) hydrogels with various levels of elasticity ranged in
      3-300 kPa. We found that all HCAECs reached confluence on these hydrogels while
      retaining the similar expression of EC-specific markers to that on polystyrene
      (PS), a widely used scaffold in cell culture in vitro. Real-time polymerase chain
      reaction (PCR) and glycosaminoglycan (GAG) assay showed that the amount of EC
      specific glycocalyx secreted by HCAECs cultured on PNaSS gels was higher than
      that cultured on PS, and it increased with an increase of gel elasticity.
      Furthermore, the HCAECs cultured on PNaSS gels showed excellent property against
      platelet adhesion and lower surface friction than that on PS. The platelet
      adhesion and surface friction of HCAECs cultured on PNaSS gels also depend on the
      elasticity of gels. The largest amount of EC-specific glycocalyx, excellent blood
      compatibility, and the lowest friction were observed when the elastic modulus of
      the gel was larger than 60 kPa. Overall, HCAECs cultured on these hydrogels have
      better properties than those cultured on PS scaffold, demonstrating the PNaSS
      gels can be used as potential tissue engineering material for blood vessels.

PMID- 20681031
TI  - 22-oxa-1,25-dihydroxyvitamin D3 efficiently inhibits tumor growth in inoculated
      mice and primary histoculture of cholangiocarcinoma.
AB  - BACKGROUND: It is well known that 1alpha,25-Dihydroxyvitamin D3 (1,25[OH]2 D3)
      restrains cell proliferation and induces differentiation and apoptosis in normal
      and tumor cells. The authors of this report recently demonstrated that 1,25(OH)2
      D3 effectively inhibits the proliferation of cholangiocarcinoma (CCA) cell lines.
      The antitumor activity and the underlying mechanism of 22-oxa-D3, an analog of
      vitamin D, in mice and in tissue cultures from patients with CCA were further
      explored in the current study. METHODS: Cell growth and cell cycle distribution
      were examined in CCA cells by 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay and flow cytometry. Mice were injected
      subcutaneously with 4*10(6) CCA cells at both flank sides and intraperitoneal
      injections with phosphate-buffered saline or 22-oxa-D3 (15 MUg/kg/day) for 17
      days thereafter. Tumors were removed the next day. The expression levels of
      cyclin D1 and the cyclin-dependent kinase inhibitor p21 were determined by
      Western blot analysis and immunohistochemistry. Growth inhibition of 22-oxa-D3 in
      fresh tissue samples from patients with CCA was analyzed by using a histodrug
      response assay. RESULTS: 22-oxa-D3 effectively suppressed the growth of CCA cell
      lines in a time-dependent and dose-dependent manner. 22-oxa-D3 arrested CCA cells
      at G1 phase to S phase by the suppression of cyclin D1 expression and the up
      regulation of p21. Supplementation of 22-oxa-D3 to CCA-inoculated mice
      significantly inhibited tumor growth without hypercalcemia or serious side
      effects. The treatment also induced cellular apoptosis in tissue samples from
      patients with CCA. CONCLUSIONS: 22-oxa-D3 effectively suppressed tumor growth in
      CCA-inoculated mice and induced cellular apoptosis in tissue samples from
      patients with CCA. The current data encourage further investigation of 1,25(OH)2
      D3 or its analogues as therapeutic agents in the treatment of patients with CCA.

PMID- 20681032
TI  - A phase 2 study of the oral mammalian target of rapamycin inhibitor, everolimus,
      in patients with recurrent endometrial carcinoma.
AB  - BACKGROUND: Dysregulation of phosphatase and tensin homolog (PTEN) and the gene
      that encodes the p110alpha catalytic subunit of phosphatidylinositol-3-kinase
      (PI3K), PIK3CA, are the most common mutations in endometrial carcinoma (EC). Loss
      of PTEN or activation of PIK3CA results in constitutive activation of AKT, which
      leads to up-regulation of mammalian target of rapamycin (mTOR). Everolimus is an
      oral rapamycin analog that acts by selectively inhibiting mTOR. METHODS: A single
      institution, open-labeled, phase 2 study of everolimus in patients with
      measurable recurrent EC who had failed at least 1 and no more than 2 prior
      chemotherapeutic regimens was performed. Everolimus was administered at a dose of
      10 mg orally daily for 28-day cycles. Patients were treated until disease
      progression or toxicity. The primary endpoint was clinical benefit response
      (CBR), defined as a confirmed complete or partial response or prolonged stable
      disease (SD) (>=8 weeks). Inclusion was limited to patients with endometrioid
      histology. RESULTS: A total of 35 patients were enrolled (median age, 58 years;
      range, 38-81 years). A total of 81 cycles were administered. Twelve of 28 (43%)
      evaluable patients had not developed disease progression at the time of the first
      objective evaluation (8 weeks). All these patients had SD (median, 4.5 cycles;
      range, 2-10 cycles). Six of the 28 (21%) patients had a confirmed CBR at 20 weeks
      of therapy. Patients with CBR discontinued treatment because of toxicity (6
      patients), disease progression (5 patients), and noncompliance (1 patient). Seven
      patients were unevaluable after receiving <=1 cycle because of toxicity (5
      patients) or noncompliance (2 patients). The most common drug-related toxicities
      were fatigue, anemia, pain, lymphopenia, and nausea. CONCLUSIONS: Everolimus
      demonstrated encouraging single-agent CBR in pretreated patients with recurrent
      endometrioid EC. Future studies will evaluate this agent in combination with
      hormonal and/or cytotoxic therapy.

PMID- 20681034
TI  - GM crop trial changes.

PMID- 20681033
TI  - CPT fee differentials and visit upcoding under Medicare Part B.
AB  - Medicare Part B pays outpatient physicians according to the billed Current
      Procedural Terminology (CPT) codes, which differ in procedure and intensity.
      Since many performed services merely differ by intensity, physicians have an
      incentive to upcode services to increase profitability of a visit. Using
      nationally representative data from the 2001 to 2003 Medicare Current Beneficiary
      Survey, this paper explores the effect of Medicare Part B fee differentials on
      the upcoding of general office visits (i.e. for established patient visits with
      CPT codes of 99212-99215). It finds strong evidence that these fee differentials
      influence physician's coding choice for billing purposes across a variety of
      specialties. For general office visits, Medicare outlays attributable to upcoding
      may sum to as much as 15% of total expenditures for such visits. Medicare has
      much to gain financially by clarifying its classification rules. Until the
      distinctions between types of Medicare visits are redefined in a way that
      eliminates ambiguity, upcoding under Medicare Part B is likely to continue.

PMID- 20681035
TI  - The heat is on.

PMID- 20681036
TI  - Right rare whales.

PMID- 20681037
TI  - Cliff hanger.

PMID- 20681038
TI  - Bjorn Brembs.

PMID- 20681039
TI  - Reproductive endocrinology: High-dose cabergoline improves pregnancy rates in
      women with prolactinomas.

PMID- 20681040
TI  - Cancer: MicroRNA expression provides clues about the aggressiveness of papillary
      thyroid carcinoma.

PMID- 20681041
TI  - Diabetes: Regular self-monitoring of blood glucose needed for metabolic control.

PMID- 20681042
TI  - Obesity: Maternal weight linked to congenital anomalies in offspring.

PMID- 20681043
TI  - Bone: Bisphosphonate use and atypical femur fractures.

PMID- 20681044
TI  - [The metabolic syndrome in daily clinic].

PMID- 20681045
TI  - [Danish data document therapeutic effect differences of tumor necrosis factor
      inhibitors in patient with rheumatoid arthritis].

PMID- 20681047
TI  - Surgery: Endovascular repair of abdominal aortic aneurysm--the importance of long
      term follow-up data.

PMID- 20681048
TI  - Timing of alteplase for acute stroke.

PMID- 20681049
TI  - Acute coronary syndromes: New blood tests improve risk assessment and early
      diagnosis of AMI.

PMID- 20681050
TI  - Atrial fibrillation: Obesity increases risk of AF in women.

PMID- 20681051
TI  - Hypertension: Careful monitoring of kidney function is needed in patients with
      hypertension.

PMID- 20681052
TI  - Cardiac device implantation risks.

PMID- 20681053
TI  - Transplantation: A noninvasive strategy to monitor rejection in patients with a
      heart transplant.

PMID- 20681054
TI  - Prevention: Fibrates reduce risk of coronary events.

PMID- 20681055
TI  - Natural killer cells during primary varicella zoster virus infection.

PMID- 20681056
TI  - Pulmonary hydatid disease: is capitonnage mandatory following cystotomy?
AB  - Pulmonary hydatid disease still remains an important healthcare problem.
      Conservative operative interventions including cystotomy or cystotomy with
      capitonnage are the two commonly used techniques. There is still significant
      controversy, however, over selection of these two procedures. In this
      retrospective analysis of 66 patients with hydatid disease, we employed three
      types of interventions, Group A, (n = 5) cystotomy alone with closure of
      bronchial openings; Group B, (n = 54) cystotomy with capitonnage and Group C, (n
      = 7) lobectomy over a period of seven years in our patients and compared their
      postoperative outcome in terms of morbidity and mortality. Our data show that
      cystotomy with capitonnage is associated with low rates of postoperative
      prolonged air leak, bronchopleural fistula formation, empyema formation [mean
      complication rate 0.12% (Mean 0.08; 0.151-95% CI)] as compared to cystotomy alone
      with closure of bronchial openings [mean complication rate 44% (Mean 2.20; 3.18
      95% CI)]. The lobectomy group was excluded from the comparison, as this approach
      is quite different from the cystostomy based enucleation techniques. We conclude
      that capitonnage with cystotomy may be a preferred procedure due to its lower
      rate of complications.

PMID- 20681057
TI  - The role of monocyte chemoattractant protein MCP1/CCL2 in neuroinflammatory
      diseases.
AB  - Inflammatory response represents one of the first immune processes following
      injury. It is characterized by the production of various molecules that initiate
      the recruitment of immune cells to the lesion sites, including in the brain.
      Accordingly, in acute brain trauma, such as stroke, as well as during chronic
      affections like multiple sclerosis or Alzheimer's disease, inflammation occurs in
      order to "clean up" the lesion and to limit its area. Nevertheless, prolonged and
      sustained inflammation may have cytotoxic effects, aggravating the incidence and
      the severity of the disease. Among molecules produced during inflammation
      associated to neuronal death, monocyte chemoattractant proteins (MCPs) seem to be
      particularly important. This review will focus on the current knowledge about one
      of the MCPs, CCL2, and its cognate receptor, CCR2, both expressed in
      physiological conditions and during neurodegenerative diseases.

PMID- 20681058
TI  - The 13th Annual International Conference on Gastrointestinal Research and the
      International Conference on Ulcer Research (ICGR/ICUR). Preface.

PMID- 20681059
TI  - The future of the International AIDS Society.

PMID- 20681060
TI  - North Korea's health system in disarray.

PMID- 20681061
TI  - Norway rethinks law on use of electronic patients' records.

PMID- 20681062
TI  - Antiretroviral vaginal gel shows promise against HIV.

PMID- 20681063
TI  - The Validus Medicus and a new gold standard.

PMID- 20681064
TI  - Mile-high dreams.

PMID- 20681065
TI  - The likelihood or otherwise of continued distribution of Artefill.

PMID- 20681067
TI  - [Evolving treatment algorithms for advanced non-small-cell lung cancer: 2009
      looking toward 2012].

PMID- 20681066
TI  - [American Society of Clinical Oncology Clinical Practice Guideline update on
      chemotherapy for stage IV non-small-cell lung cancer].

PMID- 20681068
TI  - [True video-assisted thoracic surgery for early-stage non-small cell lung
      cancer].

PMID- 20681069
TI  - Therapy: Propylthiouracil use associated with severe hepatotoxicity in children.

PMID- 20681070
TI  - Differentiation: from alpha to beta.

PMID- 20681071
TI  - A new therapy for thyroid cancer?

PMID- 20681072
TI  - Obesity: Weight gain prevention.

PMID- 20681073
TI  - Pharmacotherapy: Pasireotide shows promise for the treatment of acromegaly.

PMID- 20681074
TI  - Dietary learning: both consistency and congruency matter.

PMID- 20681075
TI  - Expression and function of CXCR7 in the mouse forebrain.
AB  - The chemokine CXCL12/CXCR4 signaling system is important for the regulation of
      neuron migration in the developing forebrain. In particular it is crucial for
      correct distribution of Cajal-Retzius cells and migration of cortical
      interneurons. Here we investigated the expression of CXCR7, the second receptor
      for CXCL12, in comparison to CXCR4. We found that shifts in the expression of
      both receptors in the above cited cell populations coincide with major changes in
      their migratory behavior. Furthermore, we demonstrated that postnatally generated
      olfactory interneuron precursors express CXCR7 but not CXCR4 and that their
      distribution in the rostral migratory stream is affected by CXCR7 downregulation.
      This suggests an involvement of CXCR7 in neuronal cell migration and indicates a
      possible action of CXCR7 independently of CXCR4 as a mediator of CXCL12
      signaling.

PMID- 20681083
TI  - OzFoodNet quarterly report, 1 January to 31 March 2010.

PMID- 20681084
TI  - Dark teens and born-again martyrs: captivity narratives after Columbine.
AB  - In Columbine and its legacy, two streams of American discourse about threatening
      young people and captivity by evil forces converged: Protestant evangelical
      captivity narratives dating from the colonial period and discourse about troubled
      youth that has its origins in the mid-nineteenth century. Tales about threatening
      youth convey the extent to which young people do important work for their
      cultures, especially when they are used to shore up the bounds of normality
      against the threat of deviance. Captivity narratives provided powerful impetus
      for change after Columbine, just as they did for Protestants in seventeenth
      century New England and for nineteenth-century nativist movements. After
      Columbine, tales of adolescents captured by darkness contributed to a growing
      evangelical youth movement, effected legislation concerning the separation of
      church and state, impacted public school dress codes and behavior policies, and
      in general shaped Americans' thinking about teenage deviance and normality.

PMID- 20681085
TI  - Sufis on parade: the performance of Black, African, and Muslim identities.
AB  - For over twenty years, West African Muslims from the Murid Sufi Brotherhood have
      organized the annual Cheikh Amadou Bamba Day parade in New York City. It is a
      major site where they redefine the boundaries of their African identities, cope
      with the stigma of blackness, and counteract an anti-Muslim backlash. Rather than
      viewing religion as a subset of ethnicity, this study shows how African Murids
      interrogate the meanings of religion, race and ethnicity as intersecting
      constructs. National flags from Senegal, Islamic chants, and banners advocating
      Black solidarity all indicate a negotiation of terms. Clothes worn during the
      parade act as symbols and afford them another opportunity to work out these
      borderlands, especially in contradistinction to African American converts who
      follow a slightly different course. This article examines how their religious
      procession creates a Murid cosmopolitanism, allowing them a space in which to
      reconcile multiple belongings.

PMID- 20681086
TI  - Grasping at ontological straws: overcoming reductionism in the Advaita Vedanta
      Neuroscience dialogue.
AB  - Contemporary neuropsychology reveals that the parietal lobe contains neurons that
      are specifically attuned to the act of grasping and this act may be fundamental
      to the establishment of the phenomenal boundaries between subject and object.
      Furthermore, alterations to this process, such as the hypoactivation of this
      region during meditation or the hyperactivation associated with schizophrenia,
      may eliminate or confuse, respectively, the phenomenal boundaries between subject
      and object. Traversing disciplines, the Advaita Vedanta school of Hinduism traces
      some of its key terms for subject and object to the verbal root grah, to grasp.
      The subject is literally the grasper. Furthermore, the practice of asparsa yoga,
      the yoga of no-touch, is aimed at stopping, hypoactivating, the grasping process
      in order to transcend all subject-object boundaries. This paper will argue that
      while we have not uncovered an identity of thought, we have uncovered a
      confluence of ideas between these two disciplines. We will see that this
      confluence of ideas has not pitted the believer against the critic-not forced us
      into the great reductionism debate that has dominated so much of the interchange
      between religious studies and the sciences. This case study will illuminate some
      of the methodological ways around this reductionism battle and also the
      boundaries of both disciplines for the intellectual benefit of each.

PMID- 20681087
TI  - "Born again is a sexual term": demons, STDs, and God's healing sperm.
AB  - In this article I examine the intersection between sexuality and spirit-filled
      bodies in American Evangelicalism. I am interested in investigating two issues:
      the sexual body as a site of spiritual battle and the use of popular science,
      especially the domain of genetics, as material evidence for this spiritual
      warfare. Specifically, I trace the increasingly spiritualized framing of marital
      intercourse in evangelical literature. To follow this trajectory, I highlight the
      spiritualized dangers of transgressive sexuality as well as the sexualizing of
      spirituality in evangelical sex manuals and deliverance manuals. This article
      centers around one text, Holy Sex: God's Purpose and Plan for Our Sexuality,
      whose authors' contend that sexually transmitted diseases are, in fact, demons
      lodged in genetic material that can be transferred through body fluids and
      bloodlines. The assertions about biology and demonic affliction made throughout
      the book are extreme and would be rejected by most readers of mainstream
      evangelical sex manuals. I argue that this book, though marginal, is not an
      irrelevant text. It reflects deep-seated anxieties about sexual bodies, spiritual
      concerns, and disease. Idiosyncratic though it may seem, Holy Sex taps into wider
      uncertainties about the spiritual vulnerability of the physical body found in
      contemporary evangelical literature.

PMID- 20681088
TI  - Queer eye for the ascetic guy? Homoeroticism, children, and the making of Monks
      in late antique Egypt.
AB  - A famous instruction about children in monasteries reads: "Do not bring young
      boys here. Four churches in Scetis are deserted because of boys." Taken from the
      Sayings of the Desert Fathers, this apophthegm exposes the presence of
      homoeroticism and anxieties about the homoerotic, especially erotic encounters
      with children, in early Christian ascetic communities. This essay examines the
      construction of male sexuality in early Egyptian monasticism, focusing on the
      Sayings and the rules of the monastic leader Shenoute of Atripe It argues that
      the masculine ascetic ideal builds upon certain classical ideals of masculinity,
      especially the control of the passions, but purports to eschew classical models
      of eroticism in which the adolescent male represents the ideal sexual partner.
      However, these sources are designed to be recited or retold as edifying texts;
      despite their overt disavowal of sexual contact between men and boys, their
      retelling and rereading keeps homoeroticism and the representation of boys as
      sexually desirable objects alive in the ascetic imagination.

PMID- 20681089
TI  - Torture and Origen's hermeneutics of nonviolence.
AB  - In a world where too many people continue to be tortured without recourse to
      legal protections, nonlegislative resources for preserving human dignity amid
      dehumanizing terror are much needed. This article analyzes the hermeneutical
      exercises constructed by the influential third century Christian intellectual,
      Origen of Alexandria, to prepare himself and others for torture and martyrdom.
      These exercises were designed to be a counter-asceticism that would strike at the
      root of violence both in the self and in society and enable his contemporary
      Christians to suffer at the hands of the Romans without losing sight either of
      their own humanity or that of their tormentors. Christians following Origen's
      practice were trained to resist not only the Roman Empire's violent disciplining
      of bodies, but the whole interpretation of the world that justified it as they
      embodied a nonviolent alternative to it. In this way, Origen provides resources
      for a particularly religious mode of resistance to torture that usefully
      supplements the contemporary human rights campaign and holds promise for
      overcoming some of its limitations.

PMID- 20681090
TI  - Inca of the blood, Inca of the soul: embodiment, emotion, and racialization in
      the Peruvian mystical tourist industry.
AB  - In the context of the globalizing New Age movement and of the "turismo mistico"
      (mystical tourism) industry emanating from Peru, white and mestizo New Age
      practitioners and tourists fashion ideologies emphasizing the spiritual energy
      which supposedly resides in Quechua bodies, even as they freely appropriate
      Quechua cosmology and ritual for a hybridized New Age Andean spirituality. This
      case shows how racialized structural inequalities are expressed and experienced
      by tourists and New Age movement leaders through particular, essentialist
      representations of the body and through a common repertoire of emotional
      responses to inequality, commodification, and privilege. The paper provides an
      ethnographic account of how racialization may be perpetuated, negotiated, and
      resisted through religious systems, particularly through the work of constructing
      ideologies and experiences of the body and of emotional subjectivity.

PMID- 20681091
TI  - Pinned on Karma Rock: whitewater kayaking as religious experience.
AB  - This paper argues that whitewater paddling constitutes religious experience, that
      non-western terms often best describe this experience and that these two facts
      are related and have much to tell us about the nature of religious experience.
      That many paddlers articulate their experiences using Asian and/or indigenous
      religious terms suggests that this language is a form of opposition to existing
      norms of what constitutes religious experience. So, investigating the sport as an
      aquatic nature religion provides the opportunity to revisit existing categories.
      As a "lived religion," whitewater kayaking is a ritual practice of an embodied
      encounter with the sacred, and the sacred encounter is mediated through the
      body's performance in the water. This sacred encounter-with its risk and danger
      illustrates Rudolph Otto's equation of the sacred with terrifying and
      unfathomable mystery and provides a counterpoint to norms of North American
      religiosity and related scholarship.

PMID- 20681092
TI  - New streams of religion: fly fishing as a lived, religion of nature.
AB  - Fly fishers around the world frequently use terms such as religious, spiritual,
      sacred, divine, ritual, meditation, and conversion to describe their personal
      angling experiences. Further, drawing upon religious terminology, anglers will
      refer to rivers as their church and to nature as sacred. Often these latter
      pronouncements drive a concern for the conservation of these sacred spaces as
      evidenced by participation in both local and national conservation organizations.
      Informed by theoretical perspectives offered by religious studies, particularly
      "lived religion" and "religion and nature," I shall trace a few of the
      historical, material, and everyday elements of fly fishers and their subcultures,
      demonstrating along the way the insights that come by understanding fly fishing
      as a religious practice, which can, at times, drive an ethic of environmental
      conservation.

PMID- 20681093
TI  - Surfing into spirituality and a new, aquatic nature religion.
AB  - "Soul surfers" consider surfing to be a profoundly meaningful practice that
      brings physical, psychological, and spiritual benefits. They generally agree on
      where surfing initially developed, that it assumed a religious character, was
      suppressed for religious reasons, has been undergoing a revival, and enjoins
      reverence for and protection of nature. This subset of the global surfing
      community should be understood as a new religious movement-a globalizing,
      hybridized, and increasingly influential example of what I call aquatic nature
      religion. For these individuals, surfing is a religious form in which a specific
      sensual practice constitutes its sacred center, and the corresponding experiences
      are constructed in a way that leads to a belief in nature as powerful,
      transformative, healing, and sacred. I advance this argument by analyzing these
      experiences, as well as the myths, rites, symbols, terminology, technology,
      material culture, and ethical mores that are found within surfing subcultures.

PMID- 20681094
TI  - Secularizing the pain of footbinding in China: missionary and medical stagings of
      the universal body.
AB  - How did foreign Christian anti-footbinding activists treat the distinctive forms
      of human embodiment they encountered in China? What were their assumptions? How
      should we understand the transition from religious to secular imaginings of the
      body and its pains? Here I discuss late nineteenth and early twentieth century
      religion and medicalized hygiene through the voices of two English people who
      campaigned against and wrote extensively about footbinding. Not an easy story
      about God traded for Nature, but a far more uneasy and subliminal borrowing and
      cross-fertilization of tropes between the religious and the scientific. In both
      evangelical religion and biological science our protagonists created powerful
      narrative technologies for making cultural process disappear into nature, and
      thus to re-channel agency, making it available for new projects. Here we see the
      secular and the religious informing and reinforcing one another as moments in the
      creation of the modern.

PMID- 20681095
TI  - Religion and reproductive health and rights.
AB  - This essay examines the relationship between religion and public policy issues
      concerning reproductive health and rights. It particularly focuses on how such
      issues affect women. Although not ignoring the sometimes oppositional stance of
      some religious spokepersons to birth control and attempts to mitigate the
      suffering caused by HIV/AIDS, early or frequent pregnancy, discrimination against
      female fetuses and babies, and so on, the essay seeks to identify positive
      responses by religiously committed people, particularly women, that parallel or
      reinforce UNFPA initiatives to address such problems. The essay also attempts to
      articulate ways in which religion should come to grips with issues of
      reproductive health and rights.

PMID- 20681096
TI  - Reversing the gaze: constructing European race discourse as modern witchcraft
      practice.
AB  - In keeping with the challenge of (African American) historian of religions
      Charles Long to develop a mode of postcolonial encounter that is a process of
      mutual hermeneusis, I am proposing in this article to think "race" in terms of
      "indigenous ritual." At the very least it is an effort to relativize the western
      scientific paradigm and the universalizing humanities discourses that have
      nestled close to that paradigm. It is not an attempt to repudiate such an
      episteme but, rather-to borrow a jazz term-to "swing" it, to put it in antiphonal
      and improvisational circulation. More specifically, this article will trace a
      thought experiment, probing the historical emergence of white supremacist
      practice as a kind of modernist embodiment of "witchcraft discourse," which
      functions-in the institutional grammar it has left on deposit in contemporary
      social practice and the "intention to consume" (the substance of others) that it
      "rationalizes"-very much like the "primitive superstitions" it seeks to name and
      repudiate in positing its own rationalizing superiority. In such an enterprise,
      witchcraft, I am arguing, can be "good to think with" as a mode of communicative
      action, signifying with a kind of "boomerang effect" in the intercultural space
      of rupture between the West and the rest.

PMID- 20681097
TI  - "Magia sexualis": sex, secrecy, and liberation in modern western esotericism.
AB  - Although the forces of Eros and Magic have long been linked in western esoteric
      traditions, it is really not until the nineteenth century that we see the
      emergence of a large and sophisticated body of literature on the art of sexual
      magic. This article examines the rise of sexual magic in the late nineteenth and
      early twentieth centuries, placing it in the context of the larger discourse
      surrounding sexuality in American and British society of the Victorian era.
      Specifically, I focus on the teachings of the American spiritualist Paschal
      Beverly Randolph; the infamous "Great Beast 666," Aleister Crowley; and the
      founder of the first Tantrik Order in America, Pierre Bernard. Following the lead
      of Michel Foucault, I argue that this new literature on sexual magic was part of
      the larger interest in sex that pervaded Victorian culture. Far from being a
      period of repression and prudery, the Victorian era witnessed an unprecedented
      explosion of discourse on sex, particularly in its "deviant" and nonproductive
      forms. The rise of sexual magic at once reflects and yet also subverts many of
      the sexual values of mainstream Victorian culture. At the same time, however, I
      argue that Randolph, Crowley, and Bernard were all in their own ways somewhat
      ahead of their times and foreshadowed much of the obsession with sex and its
      liberation in contemporary America at the turn of the millennium.

PMID- 20681098
TI  - An Anglican crisis of comparison: intersections of race, gender, and religious
      authority, with particular reference to the Church of Nigeria.
AB  - The 1998 Lambeth Conference of the Anglican Communion brought into striking
      relief the two major issues dividing this particular global church: homosexuality
      and the ordination of women. Debates over these questions tend to split the
      church into its "conservative" southern dioceses and more "liberal" northern
      dioceses. With bishops from Africa and Southeast Asia now outnumbering their
      British and American counterparts, however, this rift had a surprising
      consequence at "Lambeth '98": church leaders of the northern hemisphere found
      themselves having to accept the postcolonial South's interpretation of the very
      Scripture, ecclesiastical traditions, and sexual norms the North had imposed on
      the South in the first place. This article explores the Anglican Church's
      internal struggle over women's ordination and homosexuality as a site of
      internalized and redeployed colonial tactics-as a complex of racial, economic,
      and historical forces that far exceeds the logic of "reverse colonialism."

PMID- 20681099
TI  - The damage of separation: Krishna's loves and Kali's child.
AB  - The publication of Kali's Child by Jeffrey Kripal in 1995 ignited a furious
      debate that persists unresolved today. Two questions are paramount. First, is it
      right to think of the religious and erotic realms as overlapping, particularly
      when a homosexual dimension is involved? Second, if Hindus and Hinduism are the
      subject, should non-Hindus refrain from speaking? In this article I revisit the
      Kali's Child debate by highlighting one of its central terms-vyakulata, the
      desperate agitation felt by lovers separated from the objects of their desire.
      What light is cast on Ramakrishna's same-sex longing by turning to a broader
      context: the agitation that male poets feel for Krishna when they speak through
      the female personae of his gopis? Conversely, what light might Ramakrishna's
      apparently homoerotic impulses cast on the cross-gendered moods of Krishna's male
      devotees? And what is one to make of the delight these men feel as they depict
      the sufferings of Krishna's women? Is this the dark side of Krishna's famously
      sunny world, and is it also the homosexual shadow of his dominant, flamboyant
      heterosexuality?

PMID- 20681100
TI  - A Confucian defense of gender equity.
AB  - The oppression of Chinese women is typically blamed on Confucianism. We present a
      version of Confucianism that relies on the metaphysics of the I Ching, one of the
      "canonical" Confucian texts, and on more characteristic Confucian doctrines.
      These metaphysical, anthropological, and ethical beliefs would, if fully
      implemented, replace the early Confucian hierarchy based partly on gender with a
      hierarchy based on virtue. This would in turn legitimate the full participation
      of women in society. Through the "canonical" Confucian texts we reconstruct the
      philosophical grounds for a Confucian vision of gender equity as grounded in a
      Confucian view of human nature and human excellence.

PMID- 20681101
TI  - "The Sphinx must solve her own riddle": Emerson, secrecy, and the self-reflexive
      method.
AB  - This article offers a fresh approach to the religious thought of Ralph Waldo
      Emerson, exploring (1) the particular conception of secrecy in connection with
      which he understands the human spiritual predicament and (2) his response to this
      predicament by means of a self-reflexive turn in his writing-a procedure designed
      to undermine quests for truth elsewhere and so to restore the self to the
      wholeness implicit in its initial conditions. The operation of this method will
      be traced through a number of Emerson's major works, including the second
      "Nature" (from Essays: Second Series), "History," and the poem "The Sphinx."
      Along the way, Emerson's thought will be discussed in relation to the history of
      Emerson criticism, alternative views of secrecy in religion, and the theory and
      practice of religious nondualism, to which Emerson's intellectual project bears
      considerable resemblance.

PMID- 20681102
TI  - Death, neurosis, and normalcy: on the ubiquity of personal and social delusions.
AB  - In this article Freudian theory is invoked to illustrate the connections among
      repression, the fear of death, and delusional phantasies. Civilization is a
      structure invented to protect individuals from death, but the sacrifices imposed
      by that social structure are psychologically injurious and terrifying because
      society threatens individuals with punishment and death for having illicit
      desires. Annihilation anxiety may be abated by social structures, but the
      psychological sacrifice and threat amplify annihilation anxiety. I further argue
      that immersion in personal or social phantasies quells the conscious fear of
      death. Individuals vary in terms of reactions to death anxiety and how the
      complex matrix of fear and terror is nourished or abated in the developmental
      process. A Freudian reading of the developmental process implicates the
      inherently traumatic nature of nurture and the necessity of self-deceptive
      illusions. These phantasies do subdue conscious fear, but conscious feelings of
      security do not dispel unconscious tremors. Underneath these phantasies, dread
      and terror impel rigid adherence to whatever phantasy system provides subjective
      feelings of safety and salvation.

PMID- 20681103
TI  - Women's religious conversions on death row: theorizing religion and state.
AB  - Most scholars of religion who approach the phenomena associated with religious
      conversion in order to theorize religion tend to ignore the legal and political
      implications of the actual context in which conversion occurs for theorizing
      religion itself. Meanwhile, political and legal theorists who attend to the
      implications of executing convicted murderers who undergo religious conversion on
      death row err in a different direction. They virtually ignore the significance of
      the claims made by the converts and their associates about the conversion
      themselves for theorizing the state. Scholars across disciplines increasingly
      address issues of race, class, gender, and sexual orientation in respect to
      theorizing religion and theorizing the state independently of one another. At the
      same time, they do not seize the opportunity to incorporate their analyses into a
      wider study of the sociocultural production of religion and state in relation to
      each other. I examine the religious conversion of Karla Faye Tucker and Wanda
      Jean Allen on death row, as well as the scholarship that their convictions,
      conversions, and executions have generated across academic disciplines and
      fields. Close examination illustrates well the necessity for theorizing religion
      and the state in relation to one another in order to understand either
      adequately.

PMID- 20681104
TI  - Public education and the battle over the nature of social responsibility to the
      nation's children and schools.

PMID- 20681105
TI  - Jesus, Mama, and the constraints on salvific love in contemporary country music .
AB  - The discourse of contemporary country music creates a world permeated with
      religion and centered on the notion of salvific love. This form of salvation
      arises in the connection between people (or between people and God) and includes
      elements of sacrifice and transformation. Although highly conventional, country
      music must meet standards of 'authenticity' and 'relevance', which require the
      incorporation of contemporary American religious values (including self-love and
      self-actualization). An analysis of recent country music lyrics reveals the
      remarkable openness to new religious messages. However, the only acceptable
      messages are those that can be harmonized with the implicit Protestant Christian
      sensibility of the music. Salvific love, for this reason, is always heterosexual
      and at least compatible with a Christian message. While the music industry does
      its best to erase minority sexualities, the music itself is often surprisingly
      open to a queer interpretation.

PMID- 20681106
TI  - Exe(o)rcising power: women as sorceresses, exorcists, and demonesses in
      Babylonian Jewish society of late antiquity .
AB  - This article examines talmudic discussions and archaeological finds from
      Sassanian Babylonia to explore two distinct but related topics: how some actual
      women employed ritual practices to gain power (such as the recitation of
      incantations and the use of bowls with incantations written on them) and how some
      rabbis thought about women's relationship to ritual power. First exploring
      rabbinic statements and narratives about women as sorceresses, the article then
      turns to the incantation bowls, ordinary earthenware bowls inscribed with Aramaic
      incantations, which were buried on the thresholds or in the courtyards of
      dwellings. A comparative look at these two types of sources reveals that rabbinic
      accounts of witches are actually more nuanced than the bald talmudic statement
      (b. Sanh. 67a) that "most women are sorceresses" and reveals that both the
      incantation bowls and the talmudic sources give information about women who used
      incantations and amulets to protect themselves and their families from demons and
      illness.

PMID- 20681107
TI  - Questioning dehumanization: intersubjective dimensions of violence in the Nazi
      concentration and death camps.
AB  - Using the violence in Nazi concentration and death camps as its case study, this
      article explores the theoretical and empirical limits of the concept of
      dehumanization-the process by which the perpetrators come to perceive their
      victims as "not human" or "subhuman"-and delineates appropriate alternatives to
      the concept. The author argues that excessive violence is commonly misunderstood
      and misrepresented as dehumanization because it seems to aim at effacing the
      victim's human appearance. Yet, it is more accurate to see such violence as a
      ploy to extend the perpetrator's sense of power over another human being; it is
      precisely the human quality of the interaction that provides the violence with
      much of its meaning. The argument has a moral edge, demonstrating that the
      concept ultimately reduces, or displaces, the true horror of the killer-victim
      interaction.

PMID- 20681108
TI  - The rescue of Jewish physicians in the independent state of Croatia (NDH), 1941
      1945.
AB  - Despite the murder of three-fourths of Croatia's Jews, Croatian doctors,
      representatives of the Ministry of Health, and other government figures saved 142
      Jewish physicians by mobilizing them for a mission to alleviate endemic syphilis
      in Bosnia. Twenty-seven others were recruited into the Home Guard. Along with
      members of their families, these Jews were granted "Aryan rights." In 1942 some
      began defecting to the partisans; others followed after the capitulation of Italy
      in 1943. Many died in battle, succumbed to typhus, or were murdered by the Nazis,
      the Croatian fascist Ustae, or the Serbian nationalist etniks. But the story
      recounted below shows how much better they fared than the Jewish population
      generally: sixty-two percent survived, thanks to courageous efforts by Croatian
      civilians and officials. Their rescue demonstrates both that popular attitudes
      influenced events in Yugoslavia, and that common stereotypes of Croatia during
      the war should be reconsidered.

PMID- 20681109
TI  - Far from Oblivion: the Nanking Massacre in Japanese historical writing for
      children and young adults.
AB  - The Nanking Massacre of 1937 frequently has been described as a forgotten
      genocidal act or "Holocaust." Concentrating on atrocity as reflected in Japanese
      popular historical writing for children and adolescents since the 1960s, this
      essay argues that such war crimes are far from ignored. Representations of the
      Nanking Massacre in particular, and of Japanese World War II atrocities in
      general, have been widely mobilized in Japan to inculcate an anti-war philosophy.

PMID- 20681110
TI  - Equine viral arteritis: further characterization of the carrier state in
      stallions.
AB  - Further characterization of the carrier state in stallions infected with equine
      arteritis virus revealed that there is considerable variation in the frequency of
      its occurrence among breeds. The frequency ranged from 12.5% (Holsteiner
      stallions) to 72.7% (Dutch Warmblood stallions), with a mean occurrence of 40.8%
      in the seropositive stallions (n=561) examined. More than 70% of the virus
      shedders were Standardbred stallions. The carrier state was not confirmed in any
      of the stallions that had been vaccinated against equine viral arteritis nor was
      there any evidence of intermittent virus shedding by carrier stallions. Most
      (98.2%) of the semen isolates of equine arteritis virus were obtained on first
      passage in RK-13 cell culture and most of the samples had very high virus
      infectivity titres. Intermediate term (3.5-7.0 months) and long-term (> or =1
      year) carrier states were confirmed in various horse breeds. Long-term
      persistence of equine arteritis virus in individual stallions was common, and
      some animals continued to shed the virus in semen for 4-12 years. Spontaneous
      clearance of the carrier state was observed in 27 stallions after periods ranging
      from several months to many years. There was a considerable difference in the
      rate of clearance of the carrier state between Standardbred (4.3%) and
      Thoroughbred (42.3%) stallions. Reduction and eventual elimination of the carrier
      stallion reservoir of equine arteritis virus is the key to the success of any
      control programme for this disease.

PMID- 20681111
TI  - Hydrocoele of the vaginal cavity of stallions.
AB  - The aim of the present study was to analyse the effect of hydrocoele of the
      vaginal cavity of stallions on semen characteristics, libido and fertility, and
      to contribute to the understanding of the aetiopathology of this condition in
      stallions. Hydrocoele did not substantially affect either the libido or semen
      characteristics of affected stallions compared with a control group, and had no
      effect on fertility. However, the protein content of hydrocoelic fluid was
      significantly higher than that of peritoneal fluid and was lower than the protein
      content of blood serum. Electrophoretic profiles of proteins were similar in
      peritoneal and hydrocoelic fluid. The results of the present study indicate that
      hot weather, sometimes in association with restricted exercise, age and
      communication between the vaginal and peritoneal cavities may be predisposing
      factors for hydrocoele.

PMID- 20681112
TI  - Possible role of autoimmunity to spermatozoa in idiopathic infertility of
      stallions.
AB  - Testicular degeneration is a major cause of subfertility in stallions, although
      an aetiological diagnosis cannot be made in most cases. In the present study,
      autoimmune testicular degeneration was induced and evaluated in stallions by
      immunizing stallions with their own spermatozoa mixed with an adjuvant. The
      factors evaluated included changes in semen quality and testicular histology. A
      large decrease in sperm number and quality was observed in response to sperm
      autoantigens. An ELISA test specific for antisperm antibodies was developed which
      enabled antibody titres in serum, seminal plasma and accessory sex organs to be
      measured. Serum antibodies were characterized as being specific for spermatozoa
      by absorption studies and western blotting. The data obtained and the tests
      developed in the present study provide a better understanding of the disease in
      subfertile breeding stallions and the ability to diagnose the disease using
      ELISA. The results of a clinical trial demonstrate that there is a higher
      incidence of antisperm antibodies in subfertile stallions compared with fertile
      stallions. The results of the present study indicate that autoimmunity to
      spermatozoa plays a role in idiopathic subfertility in stallions. A potentially
      useful method for tentative diagnosis of autoimmune testicular degeneration in
      subfertile stallions was also developed.

PMID- 20681113
TI  - Testicular biopsy in stallions: diagnostic potential and effects on prospective
      fertility.
AB  - Testicular biopsy was performed as a standing procedure on fertile, mature
      stallions (n=7) under sedation and local anaesthesia. The 'Biopty' instrument was
      used to collect three samples from the left testis of each stallion. The
      oestradiol, testosterone and inhibin content in each testis were assessed by
      validated radioimmunoassay (RIA); protein concentrations were determined and the
      testes were prepared histologically for haematoxylin and eosin staining. The
      fertility status of each stallion was assessed before and after testicular biopsy
      by semen evaluation, changes in total scrotal width, pregnancy rate per oestrous
      cycle, serum and seminal plasma antisperm antibody concentrations, and
      determination of plasma LH, FSH, oestradiol, testosterone and inhibin
      concentrations once a week by validated RIA. Testicular testosterone (3.85 +/-
      1.24 ng mg(-1) protein), oestradiol (3.01 +/- 0.95 ng mg(-1) protein) and inhibin
      (11.06 +/- 1.69 ng mg(-1) protein) content were measured successfully from tissue
      samples by RIA. Active spermatogenesis was evident in all histological samples.
      The mean numbers of progressively motile morphologically normal spermatozoa were
      not significantly different in the last three ejaculates of the 7 day periods of
      semen collection before (3.37 +/- 0.48 x 10(9) spermatozoa per ejaculate) and
      after (3.77 +/- 0.48 x 10(9) spermatozoa per ejaculate) testicular biopsy. Total
      scrotal width varied within normal ranges throughout the year (from 11.7 +/- 0.3
      to 10.0 +/- 0.4 cm). Pregnancy rates per oestrous cycle before (50 +/- 6%) and
      after (63 +/- 9%) testicular biopsy were not significantly different. The
      concentration of antisperm antibodies in serum and seminal plasma samples did not
      vary significantly before and after testicular biopsy. Plasma LH, FSH,
      oestradiol, testosterone and inhibin concentrations fluctuated within normal
      ranges after biopsy in the expected seasonal pattern. In conclusion, the present
      study demonstrates that using the 'Biopty' instrument to obtain testicular biopsy
      samples from stallions has no apparent detrimental effects on prospective
      stallion fertility and can be used to evaluate testicular factors and structure.

PMID- 20681114
TI  - Testicular secretion of inhibin in stallions.
AB  - In this study, clear seasonal changes in the circulating concentrations of
      immunoreactive inhibin were observed in stallions throughout the year. The
      highest plasma concentrations of immunoreactive inhibin were observed during the
      breeding season and the lowest concentrations were observed during the
      nonbreeding season. There was positive correlation between the circulating
      concentrations of immunoreactive inhibin, steroid hormones and gonadotrophins.
      Inhibin alpha subunit positive staining was observed in Sertoli cells and more
      clearly in Leydig cells. Both cell types also stained positively for inhibin
      betaA and betaB subunits. Immunoreactivity to 3beta-hydroxysteroid dehydrogenase
      and aromatase was observed in the Leydig cells only. The testes contained large
      amounts of inhibin pro-alphaC and small amounts of inhibins A and B, and the
      inhibin B content was higher than the inhibin A content. These results indicate
      that inhibin B is the major bioactive form of inhibin in equine testes. However,
      only inhibin pro-alphaC was detectable in the circulation and the inhibin pro
      alphaC concentrations changed with the concentrations of immunoreactive inhibin.
      In conclusion, both Leydig and Sertoli cells secrete testicular inhibin in
      stallions. The positive correlation observed between plasma immunoreactive
      inhibin and inhibin pro-alphaC concentrations and testicular activity during the
      breeding and nonbreeding seasons indicates that the plasma concentrations of
      these hormones are potentially useful indicators of testicular activity in
      stallions.

PMID- 20681115
TI  - Testicular and hormonal changes in stallions with thermally induced testicular
      degeneration.
AB  - The scrota of three Pony stallions and one miniature horse were insulated for 36
      h. Plasma testosterone concentrations decreased gradually and were significantly
      (P < 0.05) lower than pretreatment values at 16, 24, 30, 38 and 44 h after onset
      of scrotal insulation. Plasma LH and oestradiol concentrations were significantly
      (P < 0.05) decreased 18 h, and 24 and 26 h, after onset of scrotal insulation,
      respectively. Plasma FSH concentrations were significantly (P < 0.05) decreased 4
      days after the insulation was removed. Decreases in the potential daily sperm
      output per Pony for early primary spermatocytes (34% decrease) and late primary
      spermatocytes (60% decrease) were observed in the testes of Pony stallions
      castrated 7 days after the insulation was removed. Decreases in the potential
      daily sperm output of all germ cell types were observed in the testes of the
      miniature horse castrated 24 days after the insulation was removed. Testosterone
      propionate in corn oil (5 mg in 1.05 ml testis) was injected into the vaginal
      space surrounding the testes of two Pony stallions 2 days before scrotal
      insulation and of one stallion whose scrotum was not insulated. The percentage of
      sperm of normal morphology in ejaculates decreased significantly (P < 0.05; n=3)
      15-26 days after onset of insulation compared with pretreatment values.
      Circulating testosterone concentrations were maintained at pretreatment
      concentrations for 18 days after the scrotum was insulated, but this did not
      prevent deterioration in semen quality. Circulating LH and oestradiol
      concentrations decreased significantly by 2 days after injection of testosterone
      (P < 0.05). LH concentrations were decreased significantly (P < 0.05) from
      pretreatment values for 18 days after scrotal insulation and oestradiol
      concentrations were decreased significantly (P < 0.05) for 26 days. In
      conclusion, insulation of Pony scrota for 36 h reduced the yield of germ cells
      during spermatogenesis. A reduction in circulating testosterone concentrations
      occurred by 16 h after onset of scrotal insulation, which is probably the result
      of Leydig cell impairment. However, testosterone replacement therapy did not
      prevent deterioration of semen quality, which indicates that the primary cause of
      germ cell degeneration after thermal injury to the testes may not be impaired
      Leydig cell production of testosterone.

PMID- 20681116
TI  - Pituitary response to steroid replacement therapy in fertile, subfertile and
      infertile stallions after castration.
AB  - Recent studies in our laboratory investigating plasma gonadotrophin
      concentrations before and after castration indicate that the hypothalamic
      pituitary axis is not the original site of dysfunction in stallions with
      idiopathic infertility. In the present study, fertile, subfertile and infertile
      stallions were subjected to replacement therapy with oestradiol and testosterone
      1 year after castration to investigate hypothalamic-pituitary axis function
      further. Fertile (n=5), subfertile (n=3) and infertile (n=2) castrated stallions
      of Light horse breeds, aged 11-23 years, were given either oestradiol cypionate
      or testosterone propionate for 28 days during the breeding season. Oestradiol
      cypionate in cottonseed oil (30 mg; 6 mg ml(-1)) was administered i.m. at 2 day
      intervals starting in May for 28 days. Eight weeks after the last oestradiol
      cypionate injection, testosterone propionate in vegetable oil (85 mg; 8.5 mg ml(
      1)) was administered i.m. at 2 day intervals for 28 days. Heparinized blood
      samples were taken from the jugular vein three times a week from 3 weeks before
      the start of oestradiol cypionate treatment until 4 weeks after the last
      testosterone propionate injection. Saline or 25 microg GnRH in 1 ml saline were
      administered to the stallions on days 24 and 25, respectively, of the 28 day
      steroid treatments. Jugular blood samples were collected periodically through a
      catheter from 60 min before saline or GnRH injection until 420 min after
      injection. The plasma samples were stored at -20 degrees C until analysed for
      plasma LH, FSH, oestradiol and testosterone concentrations by validated
      radioimmunoassay. Exogenous steroid treatment increased plasma oestradiol and
      testosterone concentrations to concentrations close to normal circulating values
      (oestradiol: 49 pg ml(-1); testosterone: 1.3 ng ml(-1)) in all the groups. There
      were no significant differences in plasma LH or FSH concentrations among the
      groups during any of the treatment periods. Oestradiol treatment significantly
      increased (P < 0.05) LH concentrations, whereas testosterone treatment decreased
      LH concentrations, although the difference was not significant. Oestradiol
      treatment significantly decreased FSH concentrations (P < 0.05), whereas
      testosterone treatment significantly increased FSH concentrations (P < 0.05).
      There were no differences in LH and FSH responses to GnRH challenge among the
      three groups of stallions. In conclusion, the results of the present study
      indicate that the hypothalamic-pituitary axes in these subfertile and infertile
      stallions were not the original sites of dysfunction. Further studies at the
      testicular level are required.

PMID- 20681117
TI  - Preservation of stallion sperm quality by native phosphocaseinate: a direct or
      indirect effect?
AB  - Milk-based diluents are generally considered efficient for survival of stallion
      spermatozoa in vitro. However, milk is a complex and variable medium and native
      phosphocaseinate is a milk component that is more efficient for preservation of
      sperm motility and fertility, although the mechanisms involved in this protection
      have not yet been elucidated. The aim of the present study was to characterize
      the interactions between native phosphocaseinate and equine spermatozoa. No
      binding between sperm membranes and native phosphocaseinate was observed using
      indirect immunofluorescent staining or electron microscopy and native
      phosphocaseinate showed no indirect protective effect on spermatozoa after
      incubation in two distinct storage chambers separated by a dialysis membrane. In
      addition, the intracellular Ca2+ concentrations in spermatozoa did not alter
      after incubation in native phosphocaseinate. The favourable influence of the
      native micelle structure of the casein was observed only for spermatozoa stored
      at 15 degrees C. In conclusion, the results of the present study indicate that
      native phosphocaseinate has a direct protective effect on equine spermatozoa,
      without any evidence of binding to sperm membranes.

PMID- 20681118
TI  - Localization and cellular distribution of a unique hyaluronidase in stallion
      spermatozoa during epididymidal transit.
AB  - Three protein bands with hyaluronidase activity and molecular masses of 87, 48
      and 43 kDa were isolated from purified equine sperm plasma membranes. Indirect
      immunofluorescence was used to assess sperm labelling patterns using a polyclonal
      antibody to sperm hyaluronidase. In ejaculated spermatozoa, surface-associated
      hyaluronidase was localized to the posterior head region of 98 +/- 2% of
      spermatozoa (n=10). Epididymides were isolated from mature stallions (n=5) and
      divided into caput, corpus and cauda epididymides in separate Petri dishes. The
      epididymidal tubules were dissected and washed using Dulbecco's PBS on ice and
      spermatozoa were collected from each region in the separate Petri dishes. After
      fixation and washing, the cells were labelled using indirect immunofluorescence.
      Spermatozoa from the caput epididymidis displayed > 90% sperm head fluorescence
      over the anterior head region overlying the acrosome, whereas spermatozoa from
      the cauda epididymidis displayed fluorescence over the posterior head region
      only, which is similar to ejaculated spermatozoa. Spermatozoa from the corpus
      epididymidis displayed sperm head fluorescence similar to that of spermatozoa
      from the caput epididymidis. These data indicate that surface-associated
      hyaluronidase is redistributed during epididymidal transit and that this
      maturation-associated redistribution occurs during late transit. The results
      indicate that epididymidal sperm maturation is a dynamic event and that
      hyaluronidase could potentially be used as a novel marker for epididymal
      dysfunction in stallions.

PMID- 20681119
TI  - Exposure of progesterone receptors on the plasma membranes of stallion
      spermatozoa as a parameter for prediction of fertility.
AB  - Subfertility in stallions is attributed to the inability of spermatozoa to
      undergo the acrosome reaction in response to progesterone. In the present study,
      it was assessed whether there is a correlation between stallion fertility,
      defined on the basis of first cycle foaling rate and first cycle 'non-return
      rate', and the proportion of spermatozoa with exposed progesterone receptors on
      their plasma membranes. Semen from Dutch Warmblood (n=10) and Friesian (n=4)
      stallions was analysed. Progesterone 3-(o-carboxymethyl) oxime-BSA coupled with
      fluorescein isothiocyanate was used as a progesterone receptor probe and ethidium
      homodimer was used as a supravital stain. A high correlation was observed between
      the proportion of spermatozoa with exposed progesterone receptors and stallion
      fertility (r > 0.70; P < 0.01). This result indicates that exposure of
      progesterone receptors is a potential parameter for predicting stallion
      fertility.

PMID- 20681120
TI  - Intra- and inter-stallion variation in sperm morphology and their relationship
      with fertility.
AB  - Dismount semen samples were collected from Thoroughbred stallions during the
      breeding season to determine the magnitude and significance of the variation in
      sperm morphology within (intra-) and among (inter-) stallions. The degree of
      intra-stallion variation in sperm morphology during the breeding season was
      substantial (coefficient of variation: 20%; range 8-56%), but did not affect the
      day-to-day fertility of sperm samples taken from the same stallion (intra
      stallion). This variability did not affect the pregnancy rate of the mares with
      which each stallion was mated. The degree of interstallion variation in sperm
      morphology (coefficient of variation: 38%; range 22-79%) was greater than the
      degree of intra-stallion variation, with percentage normal spermatozoa, abnormal
      heads, detached heads, general mid-piece abnormalities, coiled tails and
      premature germ cells all being significant predictors of fertility. These results
      indicate that certain morphological features of spermatozoa (percentage of normal
      spermatozoa, abnormal or detached heads, mid-piece abnormalities, coiled tails
      and premature germ cells) influence the success of pregnancy establishment and
      may be used to predict differences in fertility among stallions.

PMID- 20681121
TI  - Biophysical and 1H magnetic resonance spectroscopy characteristics of
      fractionated stallion ejaculates.
AB  - The composition of seminal plasma must be determined to assess the possible roles
      of sex gland secretions in survival of stallion spermatozoa. In the present
      study, an automated semen collection device and 1H magnetic resonance
      spectroscopy were used to analyse and compare the composition of seminal plasma
      from fractionated and nonfractionated stallion ejaculates. The contribution of
      each semen component to the ejaculate (sequence of production of component and
      concentration) was evaluated and its relationship to biophysical parameters was
      determined. 1H magnetic resonance spectroscopy was used to quantify molecules
      defined as markers of sex gland secretions: carnitine, glycerophosphorylcholine
      and choline for the epididymides; N-acetyl function of glycoproteins and spermine
      for the ampullae; acetic acid for the bulbourethral glands; and citric acid for
      seminal vesicles. The results from 32 ejaculates (four ejaculates from each of
      four stallions by two collection methods) demonstrated the reliability of the 1H
      magnetic resonance spectroscopy quantitation, the sequence of sex gland secretion
      contributions to the ejaculate (bulbourethral glands, epididymides, ampullae and
      seminal vesicles) and the concomitant appearance of the sperm-rich fraction with
      secretions from the epididymides and ampullae.

PMID- 20681122
TI  - Motility, morphology and triple stain analysis of fresh, cooled and frozen-thawed
      stallion spermatozoa.
AB  - The aim of the present study was to determine whether there are characteristics
      of fresh, cooled and frozen-thawed semen samples that can be used to predict the
      suitability of stallion semen for preservation by cooling or freezing. Each of
      three ejaculates obtained from 12 stallions was divided into aliquots to be
      analysed for sperm motility, morphology and membrane integrity as fresh, cooled
      and frozen-thawed samples. The percentage of morphologically normal spermatozoa
      was similar in fresh and cooled samples and both were greater than in the frozen
      samples. There were no strong linear relationships in the percentages of
      progressive motility, live spermatozoa and morphologically normal spermatozoa in
      fresh, cooled and frozen-thawed semen samples. Although the percentages of motile
      spermatozoa in fresh, cooled and frozen samples were linearly related, when sperm
      motility was ranked as excellent, good, fair and poor, the only correlation
      observed was between progressive sperm motility in fresh samples and total sperm
      motility in frozen samples. The results of the present study demonstrate that the
      high percentage of progressive motility in fresh semen samples is not indicative
      of similar patterns in cooled or frozen-thawed samples. Commonly used methods for
      assessing sperm function do not appear to be useful for predicting the ability of
      stallion semen to withstand preservation by either cooling or freezing.

PMID- 20681123
TI  - Effect of antioxidants on the motility and viability of cooled stallion
      spermatozoa.
AB  - The aim of the present study was to determine whether antioxidants in semen
      extenders help to maintain the motility and viability of stallion spermatozoa
      incubated for 48 h at 5 degrees C. Semen samples were collected from ten
      stallions and washed to remove the seminal plasma. Five antioxidant treatments
      (control, xanthurenic acid, glutathione, taurine and hypotaurine) were prepared
      in each of three different semen extenders (skimmed milk, skimmed milk + egg
      yolk, and cream gel extenders). The spermatozoa were suspended in 15 treatments
      (three extenders x five treatments). Sub-samples from each sample were analysed
      for sperm motility and viability at t = 0, 24 and 48 h. Significantly higher
      percentages of motile spermatozoa were maintained over 48 h in the skimmed milk +
      egg yolk extender compared with the other treatments. The percentage of
      progressively motile spermatozoa in the skimmed milk + egg yolk extender was
      significantly higher at t=0 and 24 h (P < 0.05) and tended to be higher after 48
      h of incubation compared with the other treatments. Addition of xanthurenic acid
      to media maintained higher percentages of progressive motility and higher sperm
      velocities after 24 and 48 h incubation than did the other antioxidants (P <
      0.05). The percentages of live spermatozoa in each of the three extenders were
      similar after 0 and 24 h incubation. However, the highest percentages of live
      spermatozoa were maintained in the skimmed milk + egg yolk extender and the
      lowest percentages of live spermatozoa were maintained in the cream gel extender
      after 48 h incubation (P < 0.05). Addition of the antioxidant xanthurenic acid to
      stallion sperm extender improved the motility of stallion spermatozoa incubated
      for 48 h at 5 degrees C compared with control media.

PMID- 20681124
TI  - Effect of cholesterol on the motility and plasma membrane integrity of frozen
      equine spermatozoa after thawing.
AB  - The aim of the present study was to investigate the cryoprotectant properties of
      cholesterol after incorporation into the plasma membranes of equine spermatozoa.
      A cholesterol-methyl-beta-cyclodextrin complex was used to alter sperm plasma
      membrane cholesterol content. Ejaculates from six stallions were centrifuged in a
      non-fat skimmed milk glucose-sucrose extender (MK) or a modified Tyrode's medium
      (TALP). The sperm pellets were resuspended in the appropriate extender with or
      without added cholesterol (0.125 mmol cholesterol-methyl-beta-cyclodextrin
      complex l(-1)) and incubated at 24 degrees C for 15 min. After incubation, the
      aliquots were centrifuged and the sperm pellets were resuspended in lactose-EDTA
      egg yolk freezing extender, frozen in static nitrogen vapour and stored at -196
      degrees C. The straws were thawed and the motility and plasma membrane integrity
      of the spermatozoa were analysed. Addition of cholesterol to the incubation
      extenders improved the mean percentages of motile, progressively motile and
      rapidly motile spermatozoa in both the MK and TALP extenders containing
      cholesterol compared with extenders without cholesterol (P < 0.05). The
      percentage of spermatozoa with intact plasma membranes was higher in samples
      incubated in extenders containing cholesterol than in those without cholesterol
      (P < 0.05). The results of this study indicate that cyclodextrins can be used to
      incorporate cholesterol into equine sperm plasma membranes and that cholesterol
      incorporation imparts protection to the spermatozoa during cryopreservation.

PMID- 20681125
TI  - Effects of cryopreservation on the acrosomal status of stallion spermatozoa.
AB  - The effects of cryopreservation on the acrosomal status of equine spermatozoa
      were investigated. Ejaculates (n=10) from six stallions were processed fresh,
      after cooled storage at 4-6 degrees C for 24 h in either a milk-based or lactose
      EDTA freezing extender and after freeze-thawing in lactose-EDTA extender in
      liquid nitrogen at either 5 x 10(7) or 2 x 10(8) spermatozoa ml(-1). All samples
      were incubated in TALP-TEST for 2 h at 39 degrees C in 5% CO2. Subsamples were
      challenged with calcium ionophore A23187 for 10 min. The acrosomal status of the
      spermatozoa was evaluated by staining the spermatozoa with FITC-conjugated Pisum
      sativum agglutinin, with ethidium homodimer as a nuclear counterstain. Sperm cell
      viability was assessed with Hoechst 33258. The data were analysed by a general
      linear model ANOVA (P < 0.05). Treatment with calcium ionophore did not affect
      the percentage of acrosome reactions. The samples containing 5 x 10(7) and 2 x
      10(8) spermatozoa ml(-1) that were frozen in lactose-EDTA extender in liquid
      nitrogen had higher percentages of spermatozoa in intermediate categories of
      acrosomal staining than did any other treatment. The percentage of acrosome
      reacted cells was also higher overall for these samples. The percentage of viable
      cells was lowest for the sperm samples frozen in lactose-EDTA extender, and lower
      in semen stored in either a milk-based or lactose-EDTA freezing extender than in
      fresh semen. In conclusion, freeze-thawing resulted in a high percentage of
      acrosomal changes and a significant decrease in sperm viability.

PMID- 20681126
TI  - Freezing of stallion semen: interactions among cooling treatments, semen
      extenders and stallions.
AB  - In the present study, the interactions among stallions, semen extenders and
      cooling treatments before stallion semen samples were frozen were studied. In
      Expt 1, the effects of four cooling treatments and three semen extenders were
      investigated (11 stallions x four split ejaculates), whereas in Expt 2, the
      effects of two semen extenders, two egg yolk concentrations and two glycerol
      concentrations were investigated (six stallions x five split ejaculates). Sperm
      motility after thawing was evaluated. In Expt 1, the extender x cooling treatment
      interaction was significant. Centrifugation and addition of glycerol at 22
      degrees C, followed by filling the straws at 4 degrees C and immediate freezing
      had detrimental effects in INRA82 + 2% (v/v) egg yolk + 2.5% (v/v) glycerol semen
      extender and in Gent semen extender compared with the same processes in Kenney +
      4% (v/v) egg yolk + 3.6% (v/v) glycerol semen extender. The other cooling
      treatments, including moderate cooling of semen to 4 degrees C before freezing,
      resulted in higher sperm motility and had similar effects among treatments. Semen
      samples from some stallions appeared to withstand freezing more effectively after
      some cooling treatments than other treatments. Some stallion spermatozoa
      demonstrated higher motility in Kenney semen extender, whereas other semen
      samples had the same motility in all extenders. In Expt 2, the stallion x
      extender interaction was not significant. Increasing the glycerol concentrations
      from 2.5 to 3.5% (v/v) enhanced sperm motility in semen extenders containing 4%
      (v/v) egg yolk (INRA82 and Kenney). Increasing the egg yolk concentrations from 2
      to 4% (v/v) in extenders containing 3.1-3.6% (v/v) glycerol improved sperm
      motility in Kenney semen extender only. These experiments demonstrate that there
      are possible differences in the ability of spermatozoa from different stallions
      to withstand different cooling treatments, but not necessarily in their tolerance
      to different semen extenders.

PMID- 20681127
TI  - Uncoupling of the equine reproductive axes during transition into anoestrus.
AB  - The reproductive activity of light horse mares (n=12) was monitored each day from
      3 September until 29 January, or until the mares entered anoestrus, by behaviour
      evaluation, ultrasonography and blood sampling. Follicles, corpora lutea and
      ovulation, as well as oestradiol, progesterone, and LH and FSH concentrations,
      were analysed to determine a reproductive profile for the transition into
      anoestrus. The results of the present study indicate that light horse mares
      progress through four phases during the autumn transition into anoestrus: (i)
      normal cycles; (ii) aberrant cycles; (iii) anovulation, with significant
      follicular activity; and (iv) anoestrus. One of the first changes observed was a
      progressive decrease in mean progesterone concentrations during normal cycles
      (summer: 7.1 +/- 0.4 ng ml(-1); last cycle: 3.6 +/- 0.2). Regression analysis
      indicates that large follicles progressively lose their ability to produce
      oestradiol in autumn (third last cycle: 8.5 +/- 1.3 pg ml(-1); last cycle: 5.7 +/
      0.5). During the last ovulatory surge, LH concentrations decreased approximately
      50% in 6 of 8 mares. The duration of the follicular phase increased with each
      cycle approaching anovulation. However, the diameters of the follicles ovulated
      did not differ. The duration of the luteal phase during ovulatory cycles did not
      change. Four of the 12 mares developed spontaneously prolonged corpora lutea and
      were eliminated from the analysis. An anovulatory follicular growth phase
      occurred immediately before anoestrus in 7 of 8 mares. FSH preceded follicular
      growth during all cycles and persisted throughout the anovulatory period. During
      anoestrus, plasma oestradiol, progesterone and LH concentrations remained at
      basal concentrations. FSH concentrations remained high in 3 of 8 mares but did
      not cause follicular growth. It is concluded that ovarian and pituitary events
      become uncoupled during the transition into anoestrus.

PMID- 20681128
TI  - Relationship between thyroid function and seasonal reproductive activity in
      mares.
AB  - The relationship between thyroid function and seasonal reproductive activity in
      mares was investigated by comparing plasma triiodothyronine and thyroxine
      concentrations in anoestrous mares and in mares with cyclic ovarian activity
      during the anovulatory season. In study 1, the diurnal changes in plasma
      triiodothyronine and thyroxine concentrations on a single day were compared in
      anoestrous and cyclic mares. The mean thyroxine concentrations were significantly
      higher (P < 0.001) in the cyclic mares than in the anoestrous mares, whereas mean
      triiodothyronine concentrations were similar in both groups. In study 2, plasma
      thyroid hormone concentrations were monitored in mares that foaled before the
      vernal equinox. Nine mares resumed cyclic ovarian activity shortly after
      parturition and ten mares remained in anoestrus. Mean plasma triiodothyronine and
      thyroxine concentrations were significantly lower in the first 60-90 days after
      foaling in the mares undergoing anoestrus than in the mares undergoing normal
      ovarian activity after parturition (P < 0.001). In these mares, the increases in
      triiodothyronine and thyroxine concentrations were associated with the first
      ovulation after parturition. In study 3, thyroid hormone concentrations were
      monitored in adult (n=14) and young (n=14) mares. Mean thyroxine concentrations
      were significantly lower in adult anoestrous mares during the anovulatory period
      than in cyclic mares and in anoestrous mares before and after the anovulatory
      period (P < 0.01). Mean plasma triiodothyronine concentrations were also
      significantly lower (P < 0.001) in anoestrous mares from December until March.
      There were no significant differences between the plasma triiodothyronine and
      thyroxine concentrations in young cyclic and anoestrous mares. This relationship
      between thyroid function and expression of seasonal reproductive activity does
      not indicate that the thyroid gland is involved in the control of seasonality in
      horses. The decreased triiodothyronine and thyroxine concentrations in anoestrous
      mares may be the result of a hypothalamic control similar to that described for
      seasonal reproductive activity.

PMID- 20681129
TI  - Dopamine antagonist-induced reproductive function in anoestrous mares:
      gonadotrophin secretion and the effects of environmental cues.
AB  - The effect of the dopamine antagonist sulpiride on FSH secretion and onset of
      reproductive activity in anoestrous mares under different environmental
      conditions was investigated. In Expt 1, sulpiride (0.5 mg (-)-sulpiride kg(-1)
      twice a day) had no affect on FSH pulse frequency, mean FSH concentration, basal
      FSH concentration or FSH pulse amplitude in anoestrous mares. These data do not
      support the hypothesis that dopamine inhibits reproductive activity by
      suppressing GnRH secretion, as it does in other species. In Expt 2, the interval
      to first ovulation (14.8 +/- 1.9 days; range 12-22 days) in five mares treated
      with sulpiride (0.5 mg (-)-sulpiride kg(-1) twice a day) housed indoors under
      extended daylength (16 h light: 8 h dark) was significantly shorter (P < 0.02)
      than in six untreated mares housed indoors under extended daylength (34.3 +/-
      5.5; range 16-52 days and seven untreated mares housed outside under natural
      photoperiod (73 +/- 10; range 37-107 days). However, if the FSH secretion
      parameters at the start of treatment are treated as covariants, each has a
      significant effect (P < 0.05) on the interval to ovulation and sulpiride
      treatment does not have a significant effect. In Expt 3, the interval to first
      ovulation was not significantly different in sulpiride-treated (200 mg (-)
      sulpiride twice a day) and untreated mares maintained outside under natural
      photoperiod. These results indicate that sulpiride treatment combined with
      increased temperature (indoor housing) and stimulatory photoperiod (extended
      daylength) results in a shorter interval to first ovulation and that a
      nonstimulatory environment decreases the effect of treatment on the interval to
      first ovulation. The role of FSH secretion at the time of treatment remains to be
      determined.

PMID- 20681130
TI  - Influence of the dopamine antagonist domperidone on the vernal transition in
      seasonally anoestrous mares.
AB  - The aim of the present study was to determine the effect of prolonged
      administration of the dopamine antagonist domperidone on follicular development,
      ovulation and endocrine profiles in anoestrous mares. Anoestrous mares (n=16)
      were maintained under natural photoperiod and ambient temperature. Eight of the
      mares were treated with domperidone each day from 15 January until the first
      ovulation of the year. The mean number and size of follicles > or =20 mm in
      diameter were significantly greater in domperidone-treated mares than in control
      mares by day 14 of treatment. The day of first ovulation was significantly
      earlier in domperidone-treated mares than in control mares (mean +/- SEM: 51 +/-
      8.2 and 129 +/- 13.6 days, respectively; P < 0.01). The eight domperidone-treated
      mares all ovulated during treatment and the mean interval from the start of
      treatment to the day of first ovulation was 27 days (range 15-55 days). Six of
      the eight domperidone-treated mares underwent normal cycles after the first
      ovulation, whereas there was a prolonged interval (mean = 67 days) before the
      second ovulation in the other two mares. Domperidone administration resulted in
      significantly higher plasma prolactin concentrations measured at 0, 4, 8, 12 and
      24 h on day 7 of treatment compared with untreated controls (25.5 +/- 15.8 versus
      2.5 +/- 3.0 ng ml(-1)). The concentrations of LH and oestrogen conjugates were
      significantly higher in domperidone-treated mares compared with control mares by
      day 28 of treatment. There were no differences in FSH concentrations in
      domperidone-treated and control mares. The significant increases in follicular
      development and concentrations of oestrogen conjugates that were observed to
      occur without concurrent increases in FSH concentration indicate that either
      domperidone or prolactin may have a direct effect on the ovary.

PMID- 20681131
TI  - Opioidergic and dopaminergic effects on LH and prolactin release in pony mares at
      different times of the year.
AB  - The effects of dopaminergic and opioidergic systems on LH and prolactin release
      in Pony mares were investigated. Experiments were performed in intact mares
      during the non-breeding and the breeding seasons and in ovariectomized mares in
      November, March and May. Mares were treated with the dopamine D2-antagonist
      sulpiride, the opioid antagonist naloxone and naloxone plus sulpiride and saline.
      Naloxone alone and in combination with sulpiride increased plasma LH
      concentrations in intact anovulatory mares and in cyclic luteal phase mares,
      whereas sulpiride alone had no effect. None of the treatments influenced LH
      release in follicular phase mares. Naloxone administration significantly
      increased LH release in ovariectomized mares at all times of the year, the effect
      being most pronounced in March. Sulpiride administration increased plasma
      prolactin concentrations at all times of the year and was most pronounced in
      cyclic mares, whereas naloxone administration did not affect prolactin secretion.
      These results confirm that there are opioidergic pathways that regulate LH
      release and undergo seasonal changes in mares. No dopaminergic regulation of LH
      release or interactions between dopamine and opioids was demonstrated.

PMID- 20681132
TI  - Determination of minimum light treatment required for photostimulation of winter
      anoestrous mares.
AB  - Classical photostimulation of winter anoestrous mares consists of a light
      treatment with 14.5-16.0 h white light (100 lux), starting near the time of the
      winter solstice and ending around the time of the summer solstice. Cyclicity is
      obtained typically after about 70 days of treatment. The aim of the present study
      was to establish the minimum number of days of treatment, the lowest light
      intensity and the duration of light required per day to advance the onset of
      ovarian activity in winter anoestrous mares. In Expt 1 it was demonstrated that a
      35 day exposure to a photoperiod (14.5 h light: 9.5 h dark, 100 lux) starting at
      about the winter solstice is sufficient to advance the onset of the breeding
      season of Pony mares undergoing winter anoestrus. In Expt 2 it was established
      that a light of only 3 lux intensity inhibits an increase in melatonin
      concentrations in the evening after the usual time of switching the lights off.
      In Expt 3, a low light intensity (10 lux) produced with a 25 W white incandescent
      bulb was sufficient for photostimulation of the mares. In Expts 4 and 5, 1 h
      light (10 lux) during the photosensitive phase for 35 days advanced the onset of
      the breeding season in only half of the mares treated.

PMID- 20681133
TI  - The role of endogenous opioids in the ovulatory LH surge in mares.
AB  - Removal of opioid inhibition of GnRH neurones is thought to be a critical event
      in generating the ovulatory surge in some species. In the present study, a
      nonsurgical technique was used to collect pituitary venous blood samples from
      eight mares every 0.5-1.0 min for 1 h before and after administration of the
      opioid receptor antagonist naloxone (0.2 mg kg(-1), i.v.), to investigate whether
      opioid inhibition is also important in mares. Jugular blood samples were taken at
      10-15 min intervals. Mares were studied 0, 1 or 2 days before ovulation. Naloxone
      administration increased mean rates of GnRH (P < 0.01), LH (P < 0.001) and FSH (P
      < 0.001) secretion. The size of the increment did not vary with proximity to
      ovulation for any hormone. The amplitude of GnRH pulses rose after naloxone
      administration (P < 0.05) and the frequency and amplitude of LH pulses increased
      (frequency, P < 0.05; amplitude, P < 0.02), as did FSH pulse frequency (P <
      0.001). Jugular LH and FSH concentrations tended to rise after naloxone
      administration; however, these changes were not significant. It is concluded that
      endogenous opioids inhibit GnRH secretion during the period of increasing LH
      concentration in the ovulatory surge, thereby slowing its rate of increase. It is
      postulated that treatment with opioid antagonists could be a physiological and
      non-antigenic way to accelerate and amplify the ovulatory surge in the breeding
      season. Although a single injection of naloxone is inadequate to do this, it is
      likely that continuing antagonism, for example with a long-acting, orally-active
      analogue such as naltrexone, would maintain increased GnRH and LH secretion for
      sufficient time to raise peripheral LH concentrations and decrease the time until
      ovulation.

PMID- 20681134
TI  - Effect of oestradiol on LH secretion and pituitary responsiveness to GnRH in
      ovariectomized mares.
AB  - Long-term ovariectomized Pony mares were treated with oestradiol (0.2-5.0 mg;
      i.m.) at 12 h intervals for 10 days. Blood samples were collected by jugular
      venepuncture three times a day throughout the experiment and additional blood
      samples were collected at 15 min intervals for 12 h on days 0 and 10 (sampling
      periods 1 and 2, respectively). There were significant effects of oestradiol
      treatment (P < 0.05) and oestradiol treatment x day (P < 0.0001) on the mean LH
      concentrations each day. Regression analysis of LH time trends each day indicates
      that there is heterogeneity (P < 0.001) of regression due to the increasing LH
      concentrations in mares treated with oestradiol. These results indicate that
      oestradiol has a strong dose-related positive feedback on LH release in long term
      ovariectomized Pony mares. In Expt 2, pituitary sensitivity to GnRH in long term
      ovariectomized Pony mares after oestradiol administration was examined by
      administering a 100 mg bolus of GnRH (i.v.) twice a day on days 4 and 10 of a 10
      day period of oestradiol administration. Blood samples were collected at 30 min
      intervals for 8 h on days 4 and 10 and once a day on the other days of treatment.
      The mean LH concentrations each day increased in oestradiol-treated mares over
      the 10 days of treatment (P < 0.002) and the pituitary responsiveness to GnRH
      also increased. These results indicate that oestradiol has a strong positive
      feedback effect on LH secretion by increasing the amplitude of the LH episode.

PMID- 20681135
TI  - Ovarian secretion of inhibin in mares.
AB  - In mares, circulating immunoreactive inhibin concentrations increase during the
      follicular phase and decrease at the start of the LH surge. Thereafter, sharp
      increases in circulating immunoreactive inhibin concentrations, the 'ovulatory
      increase', are observed during ovulation. In the present study, the cellular
      sources and molecular form of ovarian inhibin were investigated to determine the
      mechanism responsible for this unique ovulatory increase. Three sizes of ovarian
      follicles (small, < 15 mm; medium, 15-30 mm; large, > 30 mm in diameter) were
      selected. Inhibin alpha-subunit was localized by immunohistochemistry to the
      granulosa cells of follicles of all sizes and the theca cells of large follicles,
      whereas inhibin betaA- and betaB-subunits were detected in the granulosa and
      theca cells of large follicles only. High concentrations of immunoreactive
      inhibin, inhibin pro-alphaC and inhibin A were detected in the follicular fluid
      of large follicles compared with small and medium follicles, whereas there were
      no significant differences in the concentrations of inhibin B in the follicular
      fluid of medium and large follicles. These results indicate that mature large
      follicles secrete large amounts of inhibins pro-alphaC and A, whereas small or
      medium follicles secrete small amounts of inhibins A, B and pro-alphaC. These
      findings also indicate that the large amount of inhibin pro-alphaC produced by
      the ovulatory follicle is the source of the ovulatory increase in the
      concentrations of circulatory immunoreactive inhibin observed during ovulation in

PMID- 20681136
TI  - Inhibin localization in equine granulosa-theca cell tumours and inhibin forms in
      tumour fluid.
AB  - The aim of this study was to examine inhibin production in granulosa-theca cell
      tumours (GTCT). The experimental aims were: (i) to determine GTCT cell types that
      produce inhibin alpha- and betaA-subunits; (ii) to determine whether alpha- and
      betaA-subunit forms differ in GTCT fluid and normal equine follicular fluid
      (eFF); and (iii) to determine whether dimeric inhibin (alpha betaA) is present in
      GTCT plasma and tumour fluid. Plasma, tumour fluid and tumour tissue were
      collected from mares (n=6) with GTCT. Plasma and eFF were collected during the
      follicular phase from mares (n=4) undergoing normal cycles. Immunohistochemical
      examination of GTCT tumour sections showed strong inhibin alpha- and betaA
      Subunit immunostaining in granulosa cells and polyhedral-shaped cells in the
      thecal-stromal layer. The presence of polyhedral-shaped cells was related to
      testosterone concentration in tumour fluid. Low molecular weight alpha-subunit
      forms were less abundant in tumour fluid than in eFF, whereas the amounts of
      betaA-subunit forms were similar in tumour fluid and eFF. Concentrations of betaA
      were increased in plasma from mares with GTCT and similar in tumour fluid and
      eFF. In summary, lower molecular weight alpha-subunit forms were less prominent
      in GTCT fluid than in eFF and concentrations of betaA were higher in GTCT plasma
      than in control plasma.

PMID- 20681137
TI  - Ovulation synchrony after follicle ablation in mares.
AB  - Two experiments were performed to determine the efficacy of ultrasound-guided
      transvaginal follicle ablation for synchronizing ovarian function in mares. The
      experiments were initiated at random stages of the oestrous cycle in control
      (nonablated) and follicle-ablated mares. On day 0, all follicles > or =10 mm in
      diameter were punctured, aspirated and curettaged in ablated mares, and, on day
      4, two doses of PGF2alpha were administered with a 12 h interval between the
      doses to both ablated and nonablated (control) mares. In Expt 1, hCG was
      administered to the ablated mares on the first or second day after the largest
      follicle was > or =30 mm in diameter. In Expt 2, hCG was administered to ablated
      mares 6 days after PGF2alpha administration, at which time the largest follicle
      was expected to be > or =30 mm in diameter. FSH concentrations increased
      initially and decreased subsequently in the ablated mares, and the ablation
      induced wave (first detection of a follicle > or =10 mm in diameter) was observed
      1.9 days after ablation and was synchronous (1-3 days) in 90% of mares. In both
      Expts 1 and 2, the uniformity of follicular wave emergence among follicle-ablated
      mares resulted in significantly better synchrony of ovulation after PGF2alpha
      administration compared with that of control mares. The variation in the interval
      from PGF2alpha administration to ovulation in ablated mares was reduced further
      by hCG administration. In the ablation + hCG groups, ovulation synchrony occurred
      6-10 days after PGF2alpha administration in Expt 1 (13/16, 81%) and 7-8 days
      after PGF2alpha administration in Expt 2 (7/8, 88%). The extended period of
      ovulation in Expt 1 compared with that of Expt 2 (5 versus 2 days) was inherent
      in the experimental design, as hCG was not administered in Expt 1 until the
      largest follicle reached > or =30 mm in diameter, whereas in Expt 2 the
      experimental design was modified such that hCG was administered 6 days after
      PGF2alpha administration. As a result, in Expt 2 all but one mare in the ablation
      + hCG group ovulated within a 2 day period; 75% (6/8) ovulated on day 8 after
      PGF2alpha administration. Combined data from Expts 1 and 2 revealed that 96%
      (22/23) of the follicle-ablated mares ovulated within 48 h of hCG administration.
      Significantly more double ovulations were detected in follicle-ablated mares
      (10/41, 24%) than in control mares (1/21, 5%). The relatively high degree of
      ovulation synchrony obtained among mares in the present study indicates that this
      procedure can be used as an alternative method to synchronize ovarian function in
      horses.

PMID- 20681138
TI  - A detailed study of hormonal profiles in mares at luteolysis.
AB  - Jugular blood samples were collected at 4 h intervals from six mares during an
      oestrous cycle to study the hormonal events that occur around the time of
      luteolysis. Blood samples from day 10 (day 0 = ovulation) until day 3 of oestrus
      were assayed for prostaglandin metabolite 13,14-dihydro-15-keto PGF2alpha (PGFM),
      oxytocin, prolactin, progesterone and oestrogen conjugates. PGF2alpha (0.5 or 1.5
      mg) was administered to six mid-dioestrous mares and the oxytocin and prolactin
      responses were measured. One to five large (peak > or =2 x nadir) pulses of PGFM,
      oxytocin and prolactin were detected in mares during the 3 day period starting on
      day 13 +/- 0.5. The first PGFM pulse was preceded or accompanied by one or more
      oxytocin pulses and, overall, large PGFM and oxytocin pulses occurred
      coincidentally (P < 0.001). During the period of oxytocin and PGFM pulses,
      progesterone concentrations decreased (P < 0.001) from mid-dioestrous to oestrous
      values. The first large prolactin pulse occurred as progesterone concentrations
      approached the nadir and preceded an increase in oestrogen conjugate
      concentrations by 1.9 +/- 0.6 days. Both PGF2alpha doses significantly increased
      prolactin concentrations, whereas only the larger dose increased oxytocin
      concentrations. It is concluded that in mares: (i) PGFM and oxytocin secretion
      patterns are consistent with the ruminant model of the initiation of luteolysis,
      in which pulsatile secretion of oxytocin from the posterior pituitary triggers
      episodic release of uterine PGF2alpha; and (ii) the timing of large prolactin
      pulses in relation to progesterone and oestrogen conjugates changes indicates
      that prolactin is more likely to have a role in follicular maturation than in
      luteolysis.

PMID- 20681139
TI  - The uterus as a source of oxytocin in cyclic mares.
AB  - In a recent study, continuous administration of oxytocin by subcutaneous minipump
      to mares from day 8 to 20 after ovulation prevented luteolysis in most of the
      treated but none of the control mares, indicating a role for oxytocin in cyclical
      luteolysis in mares. In the present study, measurement of oxytocin concentrations
      in uterine flushings recovered from nine mares during days 14-18 after ovulation
      gave values that were many times higher than those measured concurrently in
      peripheral plasma. Furthermore, intrauterine administration of oxytocin to four
      mares on day 14 after ovulation stimulated a large increase in peripheral plasma
      13,14-dihydro-15-keto PGF2alpha concentrations without a corresponding increase
      in plasma oxytocin concentrations. These findings indicate that oxytocin is
      secreted into the uterine lumen during late dioestrus and early oestrus in mares,
      where it stimulates PGF2alpha release and, thus, induces luteolysis.

PMID- 20681140
TI  - Immunolocalization of oxytocin and neurophysin in the mare uterus.
AB  - The presence of oxytocin in the mare uterus was determined by radioimmunoassay of
      tissue extracts and uterine lavage fluid, and by immunohistochemistry. Samples
      were obtained from mares during the oestrous cycle and on day 14 of pregnancy.
      Immunoreactive oxytocin was detected in extracts of endometrium and myometrium,
      and in uterine lavage fluid. In tissue sections, the luminal epithelium, the
      epithelium of the superficial, but not deep, glands, blood vessel walls and
      myometrium all stained positively for oxytocin, whereas only the luminal
      epithelium and epithelium of the superficial glands stained positively for
      neurophysin. These results indicate that oxytocin is synthesized in the
      epithelium but not in the myometrium. Immunostaining for oxytocin was most
      intense in early pregnancy and least intense during mid- to late dioestrus. The
      great variation in staining density during different reproductive states
      indicates that uterine oxytocin may have an autocrine or paracrine role in
      controlling uterine function.

PMID- 20681141
TI  - Effects of steroids on endometrial oxytocin mRNA production.
AB  - In this study, the roles of oestrogen and progesterone in the regulation of
      oxytocin gene expression in equine endometrium were examined. Anoestrous mares
      (n=19) were assigned randomly to one of the following treatment groups: control
      (vehicle control for 1 day; n=3); progesterone (250 mg progesterone per day for 6
      days; n=4); oestradiol (5 mg beta-oestradiol 17-valerate per day for 6 days;
      n=4); oestradiol plus short duration progesterone (5 mg beta-oestradiol 17
      valerate per day for 6 days followed by 250 mg progesterone per day for 6 days;
      n=4); and oestradiol plus long duration progesterone (5 mg beta-oestradiol 17
      valerate per day for 6 days followed by 250 mg progesterone per day for 12 days;
      n=4). Jugular venous blood samples were obtained for oestrogen and progesterone
      radioimmunoassays. Endometrial biopsies were obtained and total RNA was
      extracted. Expression of mRNA for oxytocin and glyceraldehyde 3'-phosphate
      dehydrogenase was assessed by RT-PCR and Southern blotting. Oxytocin mRNA
      abundance was significantly higher (P < 0.05) in the oestrogen-treated group than
      in all other groups. These data demonstrate that oestradiol priming for 6 days
      upregulated expression of the endometrial oxytocin gene. Progesterone treatment
      for either 6 or 12 days after oestradiol priming returned oxytocin mRNA abundance
      to levels similar to those of controls.

PMID- 20681142
TI  - Changes in PGF2alpha secretion during prolonged luteal phase in mares.
AB  - The aim of this study was to characterize changes in PGF2alpha secretion in mares
      with persistent corpora lutea that were induced by administering altrenogest
      during oestrus. In Expt 1, PGF2alpha secretion was compared among mares
      undergoing normal oestrous cycles (n=7) and mares undergoing prolonged luteal
      phases (n=6), using the mean 15-ketodihydro-PGF2alpha (PGFM) plasma
      concentrations, peak PGFM concentrations and number of PGFM surges each day, from
      day 12 to day 16 of the luteal phase. In Expt 2, oxytocin-induced PGF2alpha
      secretion was characterized on days 13 and 16 of the luteal phase in mares
      undergoing normal oestrous cycles (n=6) and in mares undergoing prolonged luteal
      phases (n=7) by comparing the oxytocin-induced increase in PGFM concentration and
      total PGF2alpha secretion. In Expt 1, mean PGFM concentrations, peak PGFM
      concentrations and number of PGFM surges per day were significantly lower in
      mares undergoing prolonged luteal phases than in mares undergoing normal luteal
      phases. In Expt 2, the area under the curve for PGFM ng (90 min)(-1) was similar
      for both groups on day 13 but was significantly lower on day 16 in mares
      undergoing prolonged luteal phases than in mares undergoing normal luteal phases.
      No change in total PGF2alpha secretion was observed between day 13 and 16 for
      mares undergoing normal luteal phases, but a significant decrease was observed
      from day 13 to day 16 in mares undergoing prolonged luteal phases. On days 13 and
      16, the increase in PGFM concentration 5 min after oxytocin administration was
      significantly higher in mares undergoing normal luteal phases than in mares
      undergoing prolonged luteal phases. The increase in PGFM concentration 5 min
      after oxytocin administration was similar on days 13 and 16 for mares undergoing
      normal luteal phases, but tended to be less on day 16 in mares undergoing
      prolonged luteal phases. These results indicate that failure of luteolysis in
      mares undergoing induced prolonged luteal phases is due to decreased uterine
      sensitivity to oxytocin stimulation or decreased uterine ability to secrete
      prostaglandin.

PMID- 20681143
TI  - Development of equine endometrial glands from fetal life to ovarian cyclicity.
AB  - Branched tubular endometrial glands are key features of the uterine lining in
      mares. The epithelium in the neck regions of the glands is similar to that lining
      the lumen of the uterus, whereas the epithelium in the deeper, coiled portions of
      the glands secretes protein rich histotrophe or 'uterine milk' during dioestrus
      and pregnancy. The present study was performed to characterize endometrial
      histology in perinatal and peripubertal fillies and to investigate the influences
      of specific steroid treatments on endometrial gland development in the
      prepubertal period. Uteri obtained from equine fetuses (n=5) between days 150 and
      320 of gestation, and from foals (n=5) during the first 2 months of life, were
      compared histologically with endometrial biopsies taken from yearling fillies (n
      = 8) around the onset of ovarian cyclicity. In addition, biopsies were obtained
      from two prepubertal fillies that were treated for sequential periods with
      injections of progesterone or oestradiol benzoate each day to mimic the
      peripheral hormone changes associated with puberty. At day 250 of gestation the
      luminal epithelium was starting to invaginate into the underlying stroma and, by
      day 300 of gestation, the first cross-sections of very simple tubular gland
      structures were visible. These tubular gland structures developed into clusters
      of rudimentary gland cross-sections during the early postnatal period but,
      thereafter, gland development was arrested until the epithelial invaginations
      became more obvious during the first oestrus at the onset of puberty. However,
      final differentiation and maturation of the secretory portions of the glands
      occurred only after the first ovulation. Furthermore, in prepubertal fillies this
      maturation process could not be elicited by treatment with progesterone only and
      an initial period of oestrogen priming was essential to induce full
      differentiation of the endometrial glands.

PMID- 20681144
TI  - Estimation of sodium and potassium concentrations in the uterine fluid of mares
      by microdialysis and ion chromatography.
AB  - Equine blastocyst fluid has a lower [Na+], a higher [K+] and a lower osmolality
      than does normal blood serum. Based on the assumptions that the sodium pump is
      primarily responsible for fluid accumulation and that ions transported actively
      into the blastocyst increase blastocyst osmolality above that of the external
      medium, we hypothesized that the [Na+] and the osmolality of mare uterine fluid
      are lower than those of blastocyst fluid. Microdialysis and ion chromatography
      were used to estimate [Na+] and [K+] of uterine fluid. Mares (n=10) were used for
      in vivo measurements at different stages of the oestrous cycle and during early
      pregnancy. On the basis of the results of studies in vitro, the mean +/- SD
      intrauterine [Na+] and [K+] were 110.0 +/- 15.1 and 12.3 +/- 6.8 mmol l(-1),
      respectively. These results indicate that uterine fluid of mares has a lower
      [Na+] and a higher [K+] than does normal serum. However, the [Na+] in uterine
      fluid is considerably higher than that of blastocyst fluid. Thus, these results
      do not support our hypothesis and the mechanism of production of hypotonic
      blastocyst fluid in horses remains unclear.

PMID- 20681145
TI  - Mucus production by endometrium of reproductively healthy mares and mares with
      delayed uterine clearance.
AB  - The aims of this study were to compare various staining and fixation techniques
      for endometrial biopsy samples and, thus, to investigate the mucociliary
      apparatus in endometrium from reproductively healthy mares and mares with delayed
      uterine clearance. Endometrial samples were collected from the left and right
      uterine horns of reproductively healthy mares (n=5) and mares with delayed
      uterine clearance (n=4) during anoestrus, transition, oestrus and dioestrus. Each
      sample of endometrium was fixed in either Bouin's fixative or formalin, and
      stained with alcian blue (pH 1.0 or 2.5), periodic acid Schiff (alone and in
      combination with alcian blue) or mucicarmine. An extracellular mucus blanket was
      observed more frequently in tissue fixed in Bouin's fixative than in formalin
      fixed tissue. Luminal epithelial cells and the extracellular mucus blanket were
      stained preferentially using alcian blue (pH 2.5). Ciliated cells were observed
      most readily in biopsy samples fixed with formalin and stained with either alcian
      blue (pH 2.5) or mucicarmine. Mucus production was increased in fibrotic nests
      and inflamed endometrial samples. According to image analysis, the amount of
      intracellular mucus increases during oestrus, but secretions become denser during
      dioestrus (P < 0.05). In the present study, mucus production in mares with
      delayed uterine clearance was greater than that of reproductively healthy mares
      (P < 0.05).

PMID- 20681146
TI  - The role of seminal plasma in post-breeding uterine inflammation.
AB  - The effect of seminal plasma on polymorphonuclear neutrophil (PMN) chemotaxis,
      PMN phagocytosis and complement-induced cytolysis was determined using blood
      plasma pooled from four horses and seminal plasma pooled from two stallions. To
      investigate chemotaxis, complement in blood plasma was activated with E. coli
      lipopolysaccharide in the presence of 0-50% seminal plasma diluted with a
      standardized volume of McCoy's medium and placed in a chemotactic chamber.
      Chemotaxis of blood derived equine PMNs toward the chemoattractants was
      determined after incubation at 37 degrees C for 45 min. To investigate
      phagocytosis, equine spermatozoa (5 x 10(7) ml(-1); n=5) from fertile stallions
      (n=2) were mixed with blood plasma and increasing concentrations of seminal
      plasma (50-90%). The seminal plasma was removed after opsonization at 37 degrees
      C for 30 min and 4 x 10(6) PMNs were added to the sperm cells and incubated at 37
      degrees C for 30 min. The number of phagocytosed spermatozoa per 100 PMNs and the
      proportion of PMNs that had ingested at least one spermatozoon were counted under
      a microscope. Antibody-sensitized sheep red blood cells were used to investigate
      complement-induced cytolysis. The 50% haemolytic complement activity (CH50) was
      determined in blood plasma and in the presence of increasing concentrations of
      seminal plasma (3-40%). Haemolysis was quantified by spectrophotometry at 540 nm.
      A dose-dependent inhibition of chemotaxis (P < 0.001), phagocytosis (P < 0.001)
      and complement-induced cytolysis (P < 0.001) was observed when seminal plasma was
      included in the assays. These results indicate that seminal plasma may have a
      downregulatory role in post-breeding endometritis.

PMID- 20681147
TI  - Simultaneous recording of pituitary oxytocin secretion and myometrial activity in
      oestrous mares exposed to various breeding stimuli.
AB  - The aim of this study was to investigate the effect of different breeding stimuli
      on uterine contractility and pituitary oxytocin release in five oestrous mares,
      in order to design better treatments for mares with defective physical uterine
      clearance mechanisms. Electrodes and strain gauges were implanted surgically on
      the uterine myometrium and myometrial activity was monitored with a Grass
      polygraph. A catheter was placed non-surgically in the intercavernous sinus of
      each oestrous mare to sample pituitary venous blood and a second catheter was
      placed in the jugular vein. Continuous sampling was performed for 2 h to
      determine the baseline value and during sequentially applied stimuli of: (i)
      stallion call; (ii) visual contact with a stallion; (iii) active teasing; and
      (iv) artificial insemination. No association was observed between uterine
      contraction and pituitary oxytocin release episodes during baseline recording.
      Exposure of the mares to any of the breeding stimuli was associated with rapid
      onset of myometrial contractions (P < 0.0001). The application of a stimulus
      significantly increased pituitary oxytocin release (P < 0.02) and contraction
      duration (P < 0.05), and the response to artificial insemination was greater than
      the responses to the other treatments (P < 0.05). The onset of oxytocin secretion
      was generally simultaneous with the increase in uterine contraction, rather than
      preceding it, and in some instances the responses were dissociated, making a
      cause and effect relationship less likely. In conclusion, interactions between
      stallions and mares are important components of the uterine clearance mechanism
      around the time of breeding. Knowledge of these physiological responses may be
      useful in designing therapeutic regimens for mares with endometritis due to
      defective uterine contractions.

PMID- 20681148
TI  - Oxytocin and PGF2alpha release in mares resistant and susceptible to persistent
      mating-induced endometritis.
AB  - Mares resistant (n=7) and susceptible (n=9) to persistent mating-induced
      endometritis were artificially inseminated (AI) during oestrus with chilled
      extended semen. Blood samples were collected from 30 min before AI, for 2 h after
      AI and again between 16 and 18 h after AI. Samples were assayed for oxytocin and
      the PGF2alpha metabolite 13,14-dihydro-15-keto PGF2alpha (PGFM). AI caused a
      significant increase in oxytocin concentrations in both the resistant and
      susceptible mares and there was no significant difference in oxytocin release
      between the two groups of mares. Mean PGFM concentrations were significantly
      higher in the resistant group for the first 30 min after AI. In a second
      experiment, an i.v. injection of oxytocin (1 iu per 20 kg body weight) was
      administered to both resistant and susceptible oestrous mares. Blood samples were
      collected at 5min intervals from 10 min before until 60 min after oxytocin
      administration. Administration of exogenous oxytocin caused significantly greater
      PGF2alpha release in resistant than in susceptible mares. The observed pattern of
      decreased PGFM concentrations in the susceptible group of mares after both AI and
      oxytocin administration indicates a possible defect in PGF2alpha release at the
      oxytocin receptor or post-receptor level.

PMID- 20681149
TI  - Interactions of xylazine and acepromazine with oxytocin and the effects of these
      interactions on intrauterine pressure in normal mares and mares with delayed
      uterine clearance.
AB  - The effects of the sedatives xylazine (predominantly alpha2 agonist) and
      acepromazine (predominantly alpha1 antagonist) and their influence on
      intrauterine pressure were measured in four reproductively normal mares and four
      mares with delayed uterine clearance. Intrauterine pressure was measured in each
      mare during oestrus for three 100 min periods using an 8-F catheter with three
      discrete pressure sensors. After 10 min of baseline recording, xylazine,
      acepromazine or saline was administered i.v. Oxytocin was administered i.v. after
      a further 30 min, and pressure recordings were continued for 60 min. The pressure
      changes analysed were: number of uterine contractions; time of onset and duration
      of the first contraction; and the time at which intrauterine pressure changed
      from baseline. Data were analysed using the mixed procedure of the Statistical
      Analysis System. ANOVA detected an effect of treatment (P < 0.0001) and a
      treatment by group interaction (P < 0.001). Xylazine administration caused a
      tetanic contraction in all mares. When mares with delayed uterine clearance were
      sedated with xylazine before administration of oxytocin, the duration of
      increased intrauterine pressure was longer than that of normal mares (24.87 +/-
      2.52 and 15.81 +/- 2.46, respectively; P < 0.0001). Acepromazine administration
      had no effect on the oxytocin-induced contraction pattern in normal mares, but
      there was a decrease in the number of contractions in mares with delayed uterine
      clearance. The enhanced response to alpha-agonists and -antagonists observed in
      mares with delayed uterine clearance when the drugs were administered before
      oxytocin may be due to denervation supersensitivity. After mating, sedation of
      mares with xylazine is preferred to sedation with acepromazine, as xylazine
      increases uterine contraction time.

PMID- 20681150
TI  - Functional disturbances in the endometrium of barren mares: a histological and
      immunohistological study.
AB  - Different types of endometrial maldifferentiation were investigated by
      histopathological (haematoxylin-eosin (HE), periodic acid Schiff-alcian blue and
      picro-sirius red staining) and immunohistological (oestrogen and progesterone
      receptors, Ki-67 antigen, intermediate filaments and laminin) analysis of
      endometrial biopsy specimens from mares (n=34), most of which had been barren for
      at least 1 year. Two major features were observed: (i) unequal differentiation,
      in which two functional stages are visible within a single biopsy sample: areas
      which are differentiated in accordance with the stage of the ovarian cycle and
      multiple glandular nonfibrotic foci deviating from the dominant physiological
      pattern; and (ii) irregular endometrial differentiation, in which there are
      diffuse abnormalities of functional glandular morphology that cannot be appointed
      to any physiological endometrial stage. The basic diagnosis was made in HE
      stained slides. Special stains and immunohistological analysis confirmed
      endometrial maldifferentiation concerning at least one, but mostly all, of the
      parameters investigated. Endometrial maldifferentiation was not related to the
      age or parity of mares, or to the annual season. The aetiopathogenesis and
      prognosis of endometrial maldifferentiation are not known. However, the findings
      of the present study indicate that endometrial maldifferentiation should be
      included in the routine assessment of endometrial biopsy specimens.

PMID- 20681151
TI  - Relationship between the degree of endometrial periglandular fibrosis and the
      presence of angiotensin-converting enzyme in the equine endometrium.
AB  - Endometrial periglandular fibrosis (EPF) has been proposed as a possible
      aetiology for equine embryonic and fetal loss. However, the pathophysiology of
      EPF is not well understood. Angiotensin-converting enzyme (ACE) is found in
      macrophages, endothelium (during angiogenesis) and myofibroblasts at sites of
      fibrosis in the heart, kidneys, liver and skin in several species. An increase in
      local tissue ACE-binding activity appears to be a critical event in the
      initiation and progression of fibrosis in these tissues. The aim of this study
      was to investigate the correlation between ACE activity in the equine endometrium
      and the degree of EPF, as determined by histological evaluation and morphometry
      based on a collagen-specific stain. ACE-binding activity values were
      significantly higher in the endometrial samples with moderate EPF (modified
      Kenney EPF category IIB) compared with endometria in all other categories.
      Ultrastructurally, the fibroblasts surrounding the glandular basal laminae in
      modified Kenney EPF category IIB and III endometria were undergoing
      myofibroblastic transformation-like changes. These observations indicate a
      possible link between ACE activity and the onset of EPF in mares.

PMID- 20681152
TI  - Relationship between sperm nuclear protamine free -SH status and susceptibility
      to DNA denaturation.
AB  - Data from the sperm chromatin structure assay (SCSA), a flow cytometric
      measurement of susceptibility of sperm nuclear DNA to denaturation, show strong
      correlation with the fertility potential of bulls, boars, men and stallions.
      Previous studies showed a strong relationship between stallion spermatozoa with
      denatured DNA and the presence of DNA strand breaks. In the present study, the
      relationship between stallion sperm DNA denaturation and the redox status of -SH
      groups on the cysteine residues of sperm nuclear protamines that are thought to
      stabilize chromatin was investigated. Semen samples from 30 stallions were
      evaluated by the SCSA. Aliquots of the same samples were sonicated to liberate
      sperm nuclei, purified through a 60% sucrose gradient, stained with an -SH
      specific fluorochrome (CPM (7-diethylamino-3-(4'-maleimidylphenyl)-4-methyl
      coumarin)), and the blue fluorescence of 5000 cells per sample was measured. If
      S=S bonds stabilize chromatin to inhibit DNA denaturation under the imposed low
      pH conditions, a low blue intensity would correlate with a low level of DNA
      denaturation. However, this study showed no correlation (r = -0.199, P = 0.31) of
      -SH stainability with the extent of DNA denaturation. Thus, other parameters,
      possibly DNA strand breaks, play a more significant role in susceptibility to DNA
      denaturation than the extent of S=S bonding within and between protamine
      molecules. These results also imply that rate of passage through the epididymis
      may not have significant effects on sperm fertility potential with regard to
      disulphide bonding status.

PMID- 20681153
TI  - Indirect determination of stallion sperm capacitation based on esterase release
      from spermatozoa challenged with lysophosphatidylcholine.
AB  - A spectrophotometric assay was developed to measure the amount of esterase
      released from stallion spermatozoa. This assay was used to determine the
      percentages of capacitated stallion spermatozoa, determined by the ability of
      spermatozoa to undergo an acrosome reaction and release esterase in response to a
      lysophosphatidylcholine challenge, for spermatozoa incubated under conditions to
      increase intracellular calcium and cAMP. Incubation with 100 nmol calcium
      ionophore A23187 l(-1) induced 66% of stallion spermatozoa to capacitate after 60
      min of incubation at 37 degrees C. Subsequent experiments investigating the
      effects of compounds that increase intracellular cAMP concentrations, 8-bromo
      cAMP (8bcAMP) and isobutyl-methylxanthine (IBMX), revealed that A23187 in
      combination with IBMX capacitated stallion spermatozoa after incubation for 240
      min, while the combination of A23187 + 8bcAMP + IBMX capacitated spermatozoa in
      40 min at 37 degrees C. Treating spermatozoa with a combination of compounds that
      increase intracellular calcium (A23187) and cAMP (8bcAMP and IBMX) capacitate
      stallion spermatozoa and may provide an efficient method to capacitate stallion
      spermatozoa for in vitro fertilization procedures.

PMID- 20681154
TI  - The structural morphology and epithelial association of spermatozoa at the
      uterotubal junction: a descriptive study of equine spermatozoa in situ using
      scanning electron microscopy.
AB  - Uterotubal junction tissues (n=12) recovered from young nulliparous mares 4 h
      after insemination were examined for spermatozoa in situ using scanning electron
      microscopy. Mares were inseminated before ovulation with semen containing 66-85%
      morphologically abnormal spermatozoa and approximately 1 x 10(9) progressively
      motile spermatozoa. Spermatozoa were found in all the tissues and displayed a
      variety of relationships to the epithelium, depending on regional location,
      spatial constraints and epithelial surface characteristics. Spermatozoa were most
      abundant in the epithelial folds on the uterine side of the uterotubal junction
      papilla. More than 90% of the spermatozoa had normal morphology. These
      observations indicate that morphologically normal equine spermatozoa develop
      specific associations with the luminal epithelium of the reproductive tract
      during transport to the oviduct. Furthermore, the uterine papilla of the
      uterotubal junction may be a site of preovulatory sperm storage. The scarcity of
      morphologically abnormal spermatozoa, despite their abundance in the inseminate,
      indicates that most abnormal spermatozoa either do not reach the uterotubal
      junction or do not develop normal associations with the epithelium of the
      uterotubal junction. This observation provides evidence for a mechanism of sperm
      selection during transport. Hence, both normal morphology and progressive
      motility of spermatozoa should be considered in determining insemination doses,
      particularly for subfertile stallions.

PMID- 20681155
TI  - Zona pellucida-sperm binding assay for equine oocytes.
AB  - The binding of a spermatozoon to the zona pellucida is the first step in
      fertilization. The number of spermatozoa bound to a zona pellucida may reflect
      the functional status of both the oocyte and spermatozoa. The aim of the present
      study was to determine whether the stage of maturation of the equine oocyte
      affects the capacity of the zona pellucida to bind with spermatozoa. Cumulus
      oocyte complexes (COCs) were collected from the ovaries of mares from abattoirs
      or were obtained in vivo by ultrasound-guided follicular aspiration. Oocytes were
      inseminated directly after collection or after 30 h of in vitro maturation (IVM)
      with semen from the same ejaculate. The results indicate that the immature equine
      oocytes collected from abattoirs and inseminated directly after collection bound
      fewer spermatozoa than did mature (metaphase I or II) oocytes inseminated after
      30 h of IVM. A similar correlation was observed with the oocytes collected in
      vivo. The mean number of spermatozoa bound by mature oocytes collected from
      preovulatory follicles and inseminated directly after collection was 324 +/- 29,
      whereas the mean number of spermatozoa bound by immature oocytes from
      nonpreovulatory follicles inseminated without maturation was 222 +/- 26 (P <
      0.05). This difference was not observed in the oocytes inseminated after
      maturation. It is postulated that immature equine oocytes bind fewer spermatozoa
      than do oocytes matured either in vivo or in vitro.

PMID- 20681156
TI  - Effect of cryopreservation and oviductal cell conditioned media on Ca2+ flux of
      equine spermatozoa.
AB  - Movement of Ca2+ into spermatozoa is a critically important event for
      capacitation and the acrosome reaction. In the present study, the nature of Ca2+
      movement in fresh equine spermatozoa was established and the effects of oviductal
      cell conditioned medium (OCM) and cryopreservation on Ca2+ flux were
      investigated. The ability of fresh and cryopreserved stallion spermatozoa to
      regulate Ca2+ concentration over time was evaluated in Ca2+ -free PBS.
      Intracellular Ca2+ concentrations were higher in cryopreserved spermatozoa than
      in fresh spermatozoa. However, extracellular Ca2+ concentrations were higher in
      fresh spermatozoa than in cryopreserved spermatozoa. Both fresh and cryopreserved
      spermatozoa took in 1 mmol exogenous Ca2 l(-1) immediately and rapidly, reaching
      a plateau in <5 min. The rate of Ca2+ internalization did not differ between
      fresh and cryopreserved spermatozoa. Oviductal epithelial cells from non-pregnant
      mares were incubated in TCM-199 and the OCM was harvested after 48 h to evaluate
      the effect of the OCM on sperm Ca2+ flux. Spermatozoa were incubated in either
      OCM or TCM-199 for 1 h before microscopic evaluation and Ca2+ concentration
      determination in PBS. Cryopreserved spermatozoa had higher intracellular and
      lower extracellular Ca2+ concentrations than did fresh spermatozoa, but
      incorporated Ca2+ at a slower rate than fresh spermatozoa. OCM incubation
      increased the relative intracellular Ca2+ concentration in fresh but not
      cryopreserved spermatozoa compared with spermatozoa incubated in TCM-199 (P <
      0.01). In summary, oviductal cell products affect Ca2+ internalization by equine
      spermatozoa. Cryopreservation strongly affects all aspects of sperm Ca2+ control,
      regardless of other factors. These results indicate that the high intracellular
      Ca2+ concentrations of cryopreserved stallion spermatozoa may be one of the
      reasons why mares must be inseminated very close to ovulation to maximize
      pregnancy rates using cryopreserved semen.

PMID- 20681157
TI  - Method for isolating preantral follicles from mare ovaries.
AB  - The aims of this study were to evaluate the use of collagenase treatment to
      isolate preantral follicles from mare ovaries and to assess the effect of this
      treatment on follicular morphology. Intact mare ovaries were chopped into pieces,
      incubated individually with 1, 3 or 5 mg collagenase (type 1A) ml(-1) in a
      shaking waterbath at 37 degrees C for up to 2 h and passed through a series of
      stainless steel filters with pore size 50-300 microm to remove large clumps and
      stromal cells. The samples were prepared for histological analysis and sections
      were examined by light microscopy. Isolated follicles and oocytes were measured
      and the quality of the follicles was assessed by microscopic examination. Very
      few intact preantral follicles were isolated after 30 min incubation with 1, 3 or
      5 mg collagenase ml(-l). After 60 and 90 min incubations, between eight and 71
      intact preantral follicles were isolated with 3 or 5 mg collagenase ml(-1),
      whereas very few were isolated after incubation with 1 mg collagenase ml(-1). The
      number of intact follicles isolated after incubation with either 3 or 5 mg
      collagenase ml(-1) was not significantly different. The quality of the isolated
      follicles decreased with increasing incubation time and no intact follicles were
      observed after 2 h of incubation. Preantral follicles 60-300 microm in diameter
      were isolated from ovaries after treatment with either 3 or 5 mg collagenase ml(
      1). Most of the follicles isolated were 90-150 microm in diameter. This study
      indicates that equine preantral follicles can be isolated from equine ovaries
      using collagenase and that collagenase does not have a deleterious effect on
      follicle morphology when used at the appropriate concentration for a minimum
      period. However, oocyte quality and follicle viability remain to be determined.

PMID- 20681158
TI  - Apoptosis in equine granulosa cells and its relationship to cumulus expansion and
      oocyte chromatin configuration in ovarian follicles.
AB  - During the oestrous cycle follicles grow and either ovulate or regress.
      Regressing follicles undergo atresia and in many species apoptosis has been
      identified as the underlying mechanism in this process. The aims of this study
      were to establish whether equine granulosa cells degenerate via an apoptotic
      mechanism and whether the presence of apoptotic cell death in granulosa cells is
      correlated with oocyte quality. Ovaries from mares at unknown stages of the
      oestrous cycle were obtained from an abattoir. In Expt 1, follicles (n=352) from
      37 mares were processed. DNA was extracted from granulosa cells, fractionated by
      agarose gel electrophoresis, stained with ethidium bromide and visualized with
      ultraviolet light or end-labelled with [32P]dideoxy-ATP, and autoradiography was
      performed after electrophoresis. In Expt 2, follicles (n=34) from four mares with
      at least one follicle >35 mm in diameter were processed. DNA was extracted from
      the granulosa cells; the cumulus oophorus was classified and the oocyte chromatin
      was stained with Hoechst 33,258 fluorescent stain. In Expt 1, apoptosis, as
      determined by the characteristic laddering of internucleosomal DNA fragments, was
      present in 45% of all follicles. Apoptosis was apparent primarily in follicles
      <20 mm in diameter and was present with greatest frequency in follicles 6-10 mm
      in diameter. Apoptosis was not detected in follicles >27 mm in diameter. The
      presence of sheared DNA of a wide range of different molecular masses, possibly
      indicative of necrotic cell death, was positively correlated with follicle size.
      In Expt 2, apoptosis was detected in 50% of follicles <20 mm in diameter but not
      in follicles > 30 mm in diameter. The oocytes had an expanded cumulus oophorus in
      58% of follicles <20 mm in diameter, whereas 80% of follicles > 30 mm in diameter
      had a compact cumulus oophorus. In these mares, follicles <20 mm in diameter
      appeared to undergo apoptotic changes as well as cumulus expansion. These
      findings indicate that degeneration occurs in many follicles that are not
      destined for ovulation and that detection of apoptosis can be used as an
      indicator of follicular degeneration in mares. Apoptosis, as a marker of cell
      death, can be used to study the growth and selection of follicles, and to
      correlate the health of granulosa cells with oocyte quality.

PMID- 20681159
TI  - Repeated follicle aspiration in mares: consequences for follicle growth and
      oocyte quality.
AB  - Cumulus-oocyte complexes (COCs) recovered from ovaries of mares killed at
      abattoirs or after in vivo collection have heterogeneous morphologies and meiotic
      competence as follicles of variable quality are used. It is thought that it
      should be possible to recover more uniform COCs, with respect to morphology and
      nuclear maturation, by repeated follicle aspiration. Therefore, the influence of
      repeated follicle aspiration on the number and diameter of follicles > or =5 mm
      in diameter, the morphology and recovery rate of COCs, and the chromatin
      configuration in oocytes was investigated. Repeated ultrasound-guided aspirations
      were performed on Warmblood mares (n=6) after either a normal cycle ('cyclic'
      sessions) or at 4-12 day intervals ('consecutive' sessions). In 88 follicle
      aspiration sessions, 1268 follicles were aspirated and 280 COCs were recovered:
      the mean number of follicles aspirated and the number of COCs obtained per
      session per mare were 14.4 and 3.2, respectively. The mean recovery rate was
      22.1%; there was no significant difference in the recovery rate between cyclic
      and consecutive aspirations. However, the mean number of follicles aspirated was
      significantly different between cyclic and consecutive aspirations (15.3 versus
      10.8, respectively) and, hence, fewer COCs were obtained in consecutive
      aspirations compared with cyclic aspirations (2.2 versus 3.5, respectively). The
      proportion of compact COCs was higher for consecutive than for cyclic aspirations
      (51.9 versus 28.8%, respectively; P < or = 0.02). Within consecutive sessions,
      the proportion of compact COCs decreased with increasing interval between
      aspirations. Moreover, the proportion of oocytes with a diffuse germinal vesicle
      chromatin configuration was higher in COCs collected in consecutive aspirations
      than in COCs collected in cyclic aspirations. Repeated follicle aspiration can be
      used to induce a more uniform follicular population and to provide more uniform
      COCs. The optimum interval between aspirations to provide the greatest number of
      meiotically competent oocytes must be determined.

PMID- 20681160
TI  - Ultrastructure, protein phosphorylation and mRNA status of equine oocytes matured
      in vivo and in vitro.
AB  - Equine oocytes were collected by follicle aspiration in vivo or by dissection of
      material obtained from an abattoir, and the ultrastructure, protein
      phosphorylation and mRNA status of the oocytes were evaluated. Electron
      microscopy studies indicated that the nucleus had a smooth membrane in oocytes
      with a compact cumulus, whereas the nuclear membrane was undulated in all other
      groups. Oocytes with compact cumuli had only a few microvilli, whereas those with
      expanded cumuli had more microvilli. There were only small numbers of cortical
      granules close to the oolemma in oocytes with compact cumuli and clusters of
      mitochondria were in the peripheral ooplasm. The number of mitochondria and
      cortical granules increased in oocytes with expanded cumuli and the Golgi
      complexes were smaller than in other oocytes. Oocytes were observed at 10, 20 and
      30 h of in vitro maturation. During maturation, the mitochondria migrated
      centrally and the number of cortical granules immediately below the oolemma
      increased progressively. Membrane-bound smooth endoplasmic reticulum became
      progressively less predominant. Phosphorylated proteins of molecular mass ranging
      from 20 to 150 kDa were found in oocytes and cumulus cells. The pattern of
      phosphorylated proteins was different in oocytes developed in vivo compared with
      oocytes cultured for 16 and 32 h in vitro. Cells of different cumulus types did
      not have distinct bands of phosphorylated proteins. Oocytes with compact cumuli
      had mainly repressed mRNAs, whereas the translationally active form was found in
      oocytes with expanded cumuli.

PMID- 20681161
TI  - Influence of epidermal growth factor on in vitro maturation of equine oocytes.
AB  - The effect of epidermal growth factor (EGF) on the in vitro maturation rate of
      equine oocytes was examined. Oocytes were collected from an abattoir (Expt 1) or
      using ultrasound-guided follicular puncture in vivo (Expt 2). All oocytes with a
      compact or expanded cumulus at recovery were cultured for 30 h in: medium 1
      (TCM199 + fetal calf serum (FCS) + crude equine gonadotrophin (CEG) + oestradiol
      + antibiotics); medium 2 (TCM199 + EGF); medium 3 (medium 1 without FCS + EGF);
      or medium 4 (medium 1 without CEG + EGF). In Expt 1, 84% (37/44) and 87% (40/46)
      cumulus expansion (P > 0.05), and 39% (22/57) and 9% (5/57) (P < 0.01) nuclear
      maturation, were observed in medium 1 and 2, respectively. In Expt 2, cumulus
      expansion was observed after culture in medium 1, 3 and 4 (30/30, 31/31 and
      29/29, respectively). The nuclear maturation rate was significantly lower in
      medium 3 (6%, 2/36) than in medium 1 (43%, 16/37) (P < 0.01) and was higher in
      medium 4 (64%, 25/39) than in medium 1, although the effect was not significant
      (P = 0.07). In conclusion, 50 ng EGF ml(-1) alone was an effective substitute for
      crude equine gonadotrophin and the presence of EGF improves the nuclear
      maturation rate of equine oocytes.

PMID- 20681162
TI  - Effect of timing of follicle aspiration on pregnancy rate after oocyte transfer
      in mares.
AB  - Mares with preovulatory follicles >33 mm in diameter were administered hCG and
      were randomly assigned for aspiration of the dominant follicle at 24 h or 35 h
      after hCG administration. Oocytes recovered at 24 h were cultured for 12 h before
      transfer and oocytes recovered at 35 h were cultured for 1 h. Oocytes were
      transferred by flank laparotomy to the oviduct of the same mare, or to the
      oviduct of another oocyte donor. Recipient mares were inseminated before and
      after transfer. The oocyte recovery rates at 24 h and 35 h after hCG
      administration were not significantly different (10/15 (66%) and 11/15 (73%),
      respectively) and resulted in an overall recovery rate of 70%. The overall
      pregnancy rate after transfer was 9/17 (53%) and there was no significant
      difference between groups (5/8 (63%) for the 24 h group and 4/9 (44%) for the 35
      h group). The presence of uterine fluid in recipient mares > 2 days after
      transfer was associated with a significantly lower pregnancy rate (3/10 versus
      6/7 for mares that had no fluid after day 2). This study indicates that the
      timing of oocyte collection after administration of hCG is not a major
      determinant of the pregnancy rate after oocyte transfer. Medication associated
      with follicle aspiration and oocyte transfer may increase susceptibility of
      recipient mares to endometritis, which can lower pregnancy rates if not resolved.

PMID- 20681163
TI  - Oviductal insemination of mares.
AB  - A technique was developed for oviductal insemination of mares, in which a small
      number of motile spermatozoa are deposited directly into the oviduct. Pregnancy
      rates in mares inseminated by traditional intrauterine artificial insemination
      were compared with rates in mares inseminated by oviductal insemination. Fifteen
      mares were inseminated with 5 x 10(8) progressively motile spermatozoa by
      intrauterine artificial insemination, and 14 mares were inseminated with 5 x
      10(4) progressively motile spermatozoa by oviductal insemination. Pregnancy rates
      in mares inseminated by intrauterine artificial insemination (40%) and oviductal
      insemination (21.4%) were not significantly different (P > 0.05). This study
      indicates that oviductal insemination can produce pregnancies in mares using
      10,000 times fewer spermatozoa than are used for intrauterine artificial
      insemination.

PMID- 20681164
TI  - Production of live foals from sperm-injected oocytes harvested from pregnant
      mares.
AB  - In vitro fertilization in horses has been less successful than anticipated owing
      to: (i) the inability to collect large numbers of good quality oocytes; (ii)
      alterations in the zona pellucida that occur during in vitro maturation of equine
      oocytes; and (iii) inadequate preparation of equine sperm cells. In addition,
      studies in humans, mice and cattle have indicated that high concentrations of
      glucose in culture media may inhibit embryonic development in vitro and this may
      also be a problem for development of equine embryos in vitro. The aims of the
      present study were: (i) to achieve fertilization of equine oocytes by sperm
      injection; and (ii) to determine whether culture media containing low
      concentrations of glucose are beneficial for the development of early stage
      equine IVF-derived embryos. In Expt 1, in vitro matured oocytes obtained from
      pregnant mares were subjected to intracytoplasmic sperm injection (ICSI),
      subzonal sperm injection (SUZI) or one of three control treatments. The cleavage
      rates were greater for oocytes subjected to ICSI (39%) than for oocytes subjected
      to SUZI (6%) (P < 0.05). The transfer of two embryos into one recipient mare
      resulted in the presence of an embryonic vesicle in the uterine body at day 14
      after ICSI, but it was lost subsequently between days 16 and 18 after ICSI. In
      Expt 2, oocytes were subjected to ICSI and cultured for 48 h in either TCM-199 or
      P-1(TM) medium (glucose- and phosphate-free) supplemented with 15% fetal bovine
      serum. The cleavage rates for embryos cultured in the two culture media were
      different (47% and 63% in TCM-199 and P-1(TM), respectively; P < 0.10). In
      addition, four grade 1 embryos were transferred surgically into the oviducts of
      four recipient mares 48 h after ICSI. Three pregnancies were identified by
      ultrasonography by the presence of an embryonic vesicle in the uterine body by
      day 16 after ICSI. Two of these pregnancies proceeded to term, resulting in the
      birth of two healthy fillies, one at day 319 and the other at day 328 of
      gestation.

PMID- 20681165
TI  - Pregnancies produced from fertile and infertile stallions by intracytoplasmic
      sperm injection (ICSI) of single frozen-thawed spermatozoa into in vivo matured
      mare oocytes.
AB  - The use of intracytoplasmic sperm injection (ICSI) for in vitro fertilization of
      equine oocytes and the developmental potential of these oocytes after transfer to
      the Fallopian tubes of synchronized mares were examined. Oocytes were aspirated
      from mature follicles 39 h after injection of a GnRH analogue and transported 190
      km at 39 degrees C. Semen from a fertile and an infertile stallion was frozen and
      prepared for injection. Successfully injected oocytes were transferred surgically
      into the ampulla of the Fallopian tube either: (i) 4-8 h after semen injection;
      or (ii) after 24-48 h culture before transfer. Oocytes (n=26) were treated by
      ICSI: three oocytes fragmented after injection (12%) and eight oocytes were
      returned for immediate transfer to recipient mares. Of the 15 cultured oocytes,
      eight (53%) had two polar bodies and cleaved to two-cell embryos 24 h after
      injection. Pregnancies were identified on day 12-14 after transfer in 4/16 (25%)
      recipients that had received either transferred embryos (1/8) or freshly injected
      oocytes (3/8). Two of the four pregnancies did not progress beyond day 30 and two
      mares gave birth to foals. There were no apparent differences in the
      establishment of pregnancies from oocytes injected with frozen-thawed spermatozoa
      from the fertile (3/14) or infertile stallion (1/2).

PMID- 20681166
TI  - Effects of follicular fluid or progesterone on in vitro maturation of equine
      oocytes before intracytoplasmic sperm injection with non-sorted and sex-sorted
      spermatozoa.
AB  - In Expt 1, compact cumulus oocyte complexes (COCs) were matured in: (i) control
      medium (Hepes-buffered TCM-199 with 10% oestrous cow serum (OCS) + oestradiol, LH
      and FSH); (ii) Hepes-buffered TCM-199 with 20% follicular fluid; or (iii) control
      medium containing 250 ng progesterone ml(-1). Mature oocytes were collected by
      transvaginal aspiration as a positive control for the in vitro maturation (IVM)
      treatments. Oocytes were fertilized by ICSI and cultured in Menezo's B2 + 5%
      fetal calf serum (FCS). There were no significant differences among IVM
      treatments. In Expt 2, oocytes with expanded COCs were matured in Hepes-buffered
      TCM-199 with 10% OCS, oestradiol, LH and FSH with different concentrations of
      progesterone (0, 50, 250 and 1250 ng ml(-1)). Oocytes were fertilized by ICSI and
      cultured in a chemically defined medium. The medium containing 1250 ng
      progesterone ml(-1) resulted in fewer oocytes with a visible first polar body
      after maturation (P < 0.05), whereas the media containing 0 and 50 ng
      progesterone ml(-1) resulted in higher development rates to seven- to eight-cell
      embryos (P < 0.05), compared with media containing 250 or 1250 ng progesterone
      ml(-1). Six of the resulting morulae were transferred to recipient mares. In
      addition, oocytes (n=32) from Expt 2 were injected with sex-sorted spermatozoa,
      obtained by separating X- and Y-bearing spermatozoa with a Cytomation MoFlo flow
      cytometer/cell sorter. Two embryos resulting from ICSI with X-bearing spermatozoa
      were transferred to the oviduct of a recipient mare. No pregnancies were
      established after transfer of embryos in these experiments.

PMID- 20681167
TI  - Quantitative histological analysis of equine embryos at exactly 156 and 168 h
      after ovulation.
AB  - Equine embryos were collected at exactly 156 +/- 0.5 (n=8) and 168 +/- 0.5 h
      (n=11) after ovulation. The embryos were fixed in glutaraldehyde, sectioned
      serially and observed using light microscopy. In the 156 h group, all embryos
      were early blastocysts except for one, which was a morula. The morula and one
      early blastocyst had no capsule. The capsules of the other embryos were thin. The
      mean +/- SD total number of cells was 275 +/- 105 (range 117-417). The mean +/-
      SD proportions of mitotic and pycnotic cells were 2.5 +/- 1.2 and 1.1 +/- 1.8%,
      respectively, and there were no differences between each inner cell mass (ICM)
      and trophoblast. The mean +/- SD proportion of ICM cells was 36.5 +/- 5.2%. In
      the 168 h group, there were early, mid- and expanded blastocysts, all of which
      had a capsule. The mean +/- SD total number of cells was 1093 +/- 666 (range 272
      2217). The mean +/- SD proportions of mitotic and pycnotic cells were 3.5 +/-
      1.4% and 0.1 +/- 0.03%, respectively, and there were no differences between each
      ICM and trophoblast. The mean +/- SD proportion of ICM cells was 21.1 +/- 9.7%.
      In the 168 h group, there was a significant correlation (P < 0.01) between the
      total number of cells and the diameters and proportions of ICM cells. The 168 h
      embryos were composed of significantly (P < 0.01) more cells (approximately four
      times) than were the 156 h embryos but had lower proportions of ICM cells. These
      results indicate that in equine embryos there is: (i) an individual (perhaps
      seasonal) variability in the rate of development; (ii) a doubling in the number
      of cells every 6 h between 156 h and 168 h after ovulation; and (iii) a decrease
      in the proportion of ICM cells between the early and expanded blastocyst stages
      of development.

PMID- 20681168
TI  - Differential gene expression in day 12 and day 15 equine conceptuses.
AB  - Complex changes in gene expression must occur at the proper time and in the
      appropriate tissues for pregnancy to be successful. Therefore, research aimed at
      defining the regulation of gene expression in conceptuses is of critical
      importance. However, information on developmentally regulated changes in gene
      expression in horse conceptuses is sparse and inadequate. In the present study,
      suppression subtractive hybridization was used to identify genes that are
      expressed more highly at day 15 than on day 12 of gestation. This period
      encompasses maternal recognition of pregnancy and the beginning of mesoderm
      formation and gastrulation. Clones (n=50) were isolated, partially sequenced and
      the sequences obtained were compared with known sequences to determine their
      identity. Analysis of glyceraldehyde-3-phosphate dehydrogenase and alpha
      fetoprotein (AFP) in subtracted and unsubtracted samples indicated a high
      efficiency of subtraction. Some of the genes identified included pregnancy
      associated glycoprotein (PAG), fumarylacetoacetase, cytokeratins 8 and 18, and
      isocitrate and succinate dehydrogenases. Differential gene expression of PAG and
      AFP between days 12 and 15 was confirmed. PAG expression increased approximately
      30 times and AFP expression increased at least 1000 times between days 12 and 15.

PMID- 20681169
TI  - Comparison of the cryoprotectant properties of glycerol and ethylene glycol for
      early (day 6) equine embryos.
AB  - Early (day 6) equine embryos (n=23) were assigned to four treatment groups to
      assess the cryoprotectant properties of glycerol and ethylene glycol and the
      effect of adding sucrose during removal of the cryoprotectant: (i) group GG (n=5)
      embryos were frozen and thawed using 1.5 mol glycerol l(-1) as the
      cryoprotectant, which was added at 22 degrees C in four steps (0.375, 0.75, 1.125
      and 1.5 mol glycerol l(-1)), and removed after thawing in five steps (1.5, 1.125,
      0.75, 0.375 and 0.0 mol glycerol l(-1)); (ii) group GS (n=6) embryos were frozen
      and thawed using 1.5 mol glycerol l(-1) as for group GG, except that 0.25 mol
      sucrose l(-1) was added during removal of the glycerol; (iii) group EE (n = 6)
      embryos were frozen and thawed using 1.5 mol ethylene glycol l(-1) as the
      cryoprotectant, which was added in three steps (0.5, 1.0 and 1.5 mol ethylene
      glycol l(-1)) and removed after thawing in four steps (1.5, 1.0, 0.5, 0.0 mol
      ethylene glycol l(-1)); and (iv) group ES (n = 6) embryos were frozen and thawed
      using 1.5 mol ethylene glycol l(-1) as for group EE, except that 0.25 mol sucrose
      l(-1) was added during removal of the ethylene glycol. After thawing, the embryos
      were incubated at 37 degrees C in Ham's F10 medium supplemented with 10% (v/v)
      fetal calf serum and antibiotics, in 5% CO2 in air for 6 h. The embryos were
      fixed in glutaraldehyde, serially sectioned and observed using light microscopy.
      None of the frozen-thawed embryos treated with ethylene glycol (groups EE and ES)
      had any viable cells. There were no lysed cells in the frozen-thawed embryos
      treated with glycerol (groups GG and GS) and the proportion of cells with
      pyknotic nuclei was low (group GG = 1.1 +/- 0.8% and group GS = 2.5 +/- 1.5%).
      There were no differences between embryos treated with cyroprotectant diluted
      with or without sucrose. The embryos were morulae or early blastocysts and either
      did not have a capsule or had a very thin capsule. The results of the present
      study confirm that ethylene glycol is a poor cryoprotectant for early equine
      embryos and that the use of sucrose during dilution of the cryoprotectant after
      thawing does not improve the morphology of the embryos. The results of this study
      also indicate that glycerol is an effective cryoprotectant for freezing equine
      embryos with intact zonae pellucidae and with either very thin or no capsules.

PMID- 20681170
TI  - Effect of L-glutamine for freezing equine embryos: evaluation by DAPI staining
      and transfer of multiple embryos to recipient mares.
AB  - Day 6.5 equine embryos (n=30) were frozen in a medium containing glycerol (2.5
      10.0%) supplemented with 0, 20 or 100 mmol L-glutamine 1(-1). After thawing, the
      embryos were tested individually, using 4',6'-diamidino-2-phenylindole (DAPI)
      staining to evaluate cell death. Three embryos (one frozen at each L-glutamine
      concentration) were transferred together into individual recipient mares.
      Pregnancy diagnosis was performed at day 12 (age of embryo). Embryos were
      collected at day 14 (age of embryo) and were identified by PCR amplified
      microsatellite analysis. Nine of ten recipient mares that received multiple
      embryos were pregnant: one mare was pregnant with two embryos and the other eight
      mares were pregnant with one embryo. The pregnancy rate was significantly higher
      (P < 0.05) for embryos transferred to recipient mares after freezing in media
      containing 100 mmol L-glutamine l(-1) (6 of 10 pregnancies) than for embryos
      frozen in media containing either 20 or 0 mmol L-glutamine l(-1) (1 of 10 and 3
      of 10 pregnancies, respectively). Furthermore, DAPI staining analysis indicated
      that the percentage fluorescence was significantly lower (P < 0.05) in embryos
      frozen in media containing 100 mmol L-glutamine l(-1) (4.6 +/- 2.4, n=10) than in
      embryos frozen in media containing either 20 or 0 mmol L-glutamine l(-1) (23.0 +/
      31.3 and 10.8 +/- 9.5, n=10, respectively).

PMID- 20681171
TI  - Transport of spermatozoa in the reproductive tracts of mares.
AB  - A scintigraphic method was developed to study sperm migration in the reproductive
      tracts of mares. Mares (n=5) and stallions (n=2) were used to test various steps
      of the procedure and three other mares and a stallion were used to study sperm
      transportation. A radiolabelling solution was prepared from 99mTc (Technetium
      99m) and hexamethyl propylene amine oxime. The highest labelling of spermatozoa
      (57-72%) was obtained by incubation of the spermatozoa with the radiolabelling
      solution for 20 min at 20 degrees C. Radioactivity outside the spermatozoa was
      removed by centrifugation and by two subsequent washings with skimmed milk
      extender. The labelled spermatozoa were inseminated into the uterine bodies of
      detomidine-sedated mares undergoing oestrus and scintigraphic images were
      obtained for 4.5 h after insemination. Both dynamic (two pictures s(-1), 2 min
      multiple scans, 64 x 64 matrix) and static scans (20 s, 64 x 64 matrix) were used
      to image the mares. The attenuation of gamma radiation in the vagina and uterus
      was determined for each mare. Radioactive spermatozoa were found in the tips of
      the uterine horns for the first time at about 8-20 min after insemination. The
      frequency of uterine contractions varied considerably among mares and ranged from
      five to 65 contractions during the first 30 min after insemination. Within 1 h
      after insemination most of the sperm activity was in the uterus. At 2.5 h after
      insemination, most of the spermatozoa had left the uterus and were either in the
      vagina or had escaped into the vulva and been discharged. At 4.5 h after
      insemination there was hardly any sperm activity in the uterus and a small amount
      of activity only in the vagina; most spermatozoa had been eliminated from the
      mares.

PMID- 20681172
TI  - Which insemination results in fertilization when several are performed before
      ovulation?
AB  - The aim of the present study was to determine which artificial insemination
      results in fertilization when mares are inseminated several times before
      ovulation. Mares in oestrus were inseminated over 62 cycles with fresh semen at
      48 h intervals from when a follicle > or =30 mm in diameter was detected until
      ovulation. The number of inseminations was limited to three. Three fertile
      stallions were used and a different stallion was used for each artificial
      insemination. The order of the three stallions was changed for each cycle.
      Embryos were collected between day 10 and day 12 after ovulation and paternity
      was checked using DNA typing. When two inseminations were performed per cycle, 14
      of 17 embryos were the result of the insemination performed on days 2-4 before
      ovulation and three embryos were the result of the insemination performed on days
      0-2. When three inseminations were performed, 1 of 6, 2 of 6 and 3 of 6 embryos
      resulted from the inseminations performed 4-6, 2-4 and 0-2 days before ovulation,
      respectively. Thus, 17 of 23 (74%) oocytes were not fertilized as a result of the
      insemination performed 0-2 days before ovulation. The mean interval between
      fertilization and ovulation in the mares from which embryos were recovered and
      tested (n=23) was 2.6 +/- 1.0 days. These results indicate that spermatozoa can
      remain viable in the genital tract of mares for at least 2.6 days.

PMID- 20681173
TI  - Modulation of oviductal transport in mares by local application of prostaglandin
      E2.
AB  - Equine embryos enter the uterus 144-156 h after ovulation, before which time the
      passage of embryos through the oviduct is halted in the region of the ampullary
      isthmic junction. It is thought that further onward movement of embryos to the
      uterus is facilitated by secretion of prostaglandin E2 (PGE2) by the embryos,
      which relaxes the smooth muscle of the isthmus. In the present study, the effect
      of a single local application of PGE2 on oviductal transport was examined in 22
      Thoroughbred and Pony mares that were inseminated on alternate days during
      oestrus. On day 4 after ovulation, the ipsilateral ovary, oviduct and tip of the
      uterine horn were visualized by flank laparoscopy, and either a commercial
      preparation of PGE2 suspended in a triacetin-based gel or a control gel
      containing no PGE2 was dripped along the external surface of the oviduct. On day
      5, the uterus of each mare was flushed three times with phosphate-buffered saline
      containing 1% (v/v) fetal bovine serum and, if no embryo was recovered, the
      flushing procedure was repeated on day 7 or 8. Overall, the embryo recovery rate
      was similar in PGE2-treated and control mares (65 and 63%, respectively).
      However, the recovery rate of embryos on day 5 was significantly higher for PGE2
      treated mares than for control mares (60 versus 0%; P < 0.01), indicating an
      increased rate of embryo transport in PGE2-treated mares. Furthermore,
      unfertilized oocytes were recovered from nine of the PGE2-treated mares on day 5
      but from none of the control mares. All of the embryos recovered on day 5 were
      compacted morulae, whereas all of those recovered on days 7 or 8 were expanding
      blastocysts. The results of the present study support the role of embryonic PGE2
      in oviductal transport in mares. The results also demonstrate that a single local
      application of PGE2 is a simple and practical method for speeding the passage of
      embryos through the oviduct for nonsurgical recovery of morulae from the uterus.

PMID- 20681174
TI  - Immunolocalization of a novel protein (P19) in the endometrium of fertile and
      subfertile mares.
AB  - One of the major progesterone-dependent endometrial proteins in the mare is a
      novel 19 kDa lipocalin (P19). This protein is secreted by the endometrial glands
      and is readily detectable in uterine secretions during the luteal phase of the
      oestrous cycle and early pregnancy. The function of P19 is unknown, but since
      most lipocalins act as carriers of small hydrophobic molecules, it probably
      transports a maternal factor to the conceptus during pregnancy. In this study, a
      high titre antiserum raised against recombinant-derived P19 was used to detect by
      immunohistochemistry the protein in endometrial biopsies from normal healthy
      mares and mares with endometrosis. Immunoreactive P19 was undetectable in
      prepubertal fillies and in anoestrous mares and was barely detectable in oestrous
      mares. However, it was present in large amounts during dioestrus and very early
      pregnancy, and in moderate amounts after day 20 of gestation. In six subfertile
      mares with endometrosis, an abnormal pattern was found at all stages of the
      reproductive cycle, especially in the 'gland nests'. These showed either an
      absence of P19 or an accumulation of the protein due to a lack of secretion, thus
      indicating asynchronous glandular activity. These results identified a high
      proportion of abnormal, asynchronous endometrial glands in a group of subfertile
      mares and indicated that abnormal secretion of P19 may be one of the reasons for
      the reduced fertility rates observed in aged mares with endometrosis.

PMID- 20681175
TI  - Identification of proteins in the equine embryonic capsule.
AB  - An acellular embryonic capsule envelops equine conceptuses between day 6 and day
      23 after ovulation. As all of the factors mediating embryo-mother signalling must
      pass through the capsule, it acts like a 'mailbox'. Therefore, we have started to
      map the proteins in this special extracellular matrix at the interface between
      mother and embryo. In the present study, one- and two-dimensional gel
      electrophoresis were used to examine a range of proteins. Use of western blotting
      identified three specific proteins in the capsules of equine conceptuses
      recovered on day 16 after ovulation: insulin-like growth factor binding protein 3
      (IGFBP-3), a 19 kDa uterine lipocalin (P19) and heparin-binding epidermal growth
      factor (HB-EGF). Western blotting of two-dimensional SDS-PAGE gels revealed the
      isoelectric points (pI values) of these proteins: IGFBP-3 was detected as the non
      glycosylated 32 kDa form with two isoforms at about pI value 5.8; P19 had a pI
      value of 9.1; and several isoforms of HB-EGF were detected with molecular masses
      of approximately 28 kDa and a pI value range of 5.8-6.2. The origin of HB-EGF is
      not known, but IGFBP-3 is embryonic and P19 is maternal in origin and is thought
      to be a transport protein. In addition to playing a protective role, and probably
      also contributing to the mobility of the young conceptus within the uterus, the
      capsule may be thought of as the extracellular matrix of the embryo, which
      modulates the complex embryo-maternal signalling processes that take place during
      early pregnancy in mares.

PMID- 20681176
TI  - Partial characterization of an equine conceptus prostaglandin inhibitory factor.
AB  - Equine conceptuses are thought to produce antiluteolytic factors that inhibit
      endometrial PGF2alpha and, thus, prevent luteolysis in pregnant mares. The aim of
      the present study was to characterize partially the chemical nature of the
      prostaglandin inhibitory factor (PIF) produced by equine conceptuses in vitro.
      Embryos were collected from pregnant mares 13 +/- 0.5 days after ovulation and
      were cultured for 24 h. Harvested equine conceptus conditioned media (CCM) were
      assayed for antiluteolytic activity by determining the inhibition of endometrial
      PGF2alpha synthesis in vitro. Significant antiluteolytic activity was found in
      the CCM at 12, 18 and 24 h. After size fractionation, antiluteolytic activity was
      observed in the 3-10 kDa fraction and the activity was not destroyed by
      proteinase K digestion. In contrast, treatment with dextran-coated charcoal
      removed the antiluteolytic activity from the CCM at 12, 18 and 24 h of culture (P
      < 0.05). These results indicate that the prostaglandin inhibitory factor is a low
      molecular mass (3-10 kDa) proteinase K-resistant substance that may be adsorbed
      by dextran-coated charcoal. The chemical nature, antiluteolytic activity and time
      of synthesis of the PIF by early equine conceptuses indicate that the PIF
      identified in the present study may be involved in the maternal recognition of
      pregnancy factors in mares.

PMID- 20681177
TI  - Simultaneous exocrine and endocrine secretion: trophoblast and glands of the
      endometrial cups.
AB  - Invasion of trophoblast cells of the chorionic girdle into the endometrium and
      their subsequent dependence as endometrial cup cells on the maternal vascular
      system are unique features of equine gestation. This study of exocrine secretion
      by the endometrial glands and endocrine secretion by the cup cells was initiated
      to examine the relationships between and the effects of two disparate epithelial
      cell types sharing the endometrium. Endometrial cups were examined from day 36 to
      day 83 of gestation by light and electron microscopy, and immunohistochemical and
      lectin analysis. As the cup cells invade the endometrium they migrate along the
      basal lamina of glands, thus preserving the integrity of the glands. The
      hypertrophied cup cells develop an extensive network of cytokeratin-positive
      filaments and large Golgi zones that stain positively with antibodies to equine
      chorionic gonadotrophin and with the lectins SBA (agglutinin from Glycine max)
      and WGA (agglutinin from Triticum vulgaris). The endometrial glands within and
      immediately adjacent to the cup undergo substantial hypertrophy. The gland cells
      within the cup stain with alcian blue and with some lectins (agglutinins from
      Dolichos biflorus and lectin SBA), whereas gland cells in unmodified endometrium
      away from the cup stain positively with antibodies to transforming growth factor
      a, but only poorly with SBA. Secretory material in gland luminae in the cup stain
      heterogeneously with alcian blue, periodic acid Schiff and lectins. Later in
      gestation, glands within the cup become progressively disorganized, with some
      glands rupturing and releasing their contents into the stroma of the cup. Areas
      of lipid accumulation and apparent degeneration of cup cells were observed in the
      cups on day 83 of gestation only. In conclusion, it appears that cup cells
      substantially modify the integrity and secretion of adjacent endometrial glands,
      and that progressive disruption of gland integrity and isolation of endometrial
      vessels by extracellular matrix precedes deterioration of the cup cells. Necrosis
      and disintegration resulting from these factors appear more likely to limit cup
      lifespan than to cause programmed cell death of individual cup cells.

PMID- 20681178
TI  - Differential expression of steroidogenic enzymes by the primary corpora lutea of
      pregnant mares during equine chorionic gonadotrophin secretion.
AB  - At the onset of equine chorionic gonadotrophin (eCG) secretion, eCG stimulates
      luteal androgen and oestrogen production. Although eCG concentrations increase
      exponentially from day 37 to day 60 of gestation and eCG is detectable in
      maternal serum until about day 120-150 of gestation, luteal androgen and
      oestrogen production peaks between 5 and 10 days after initial exposure to eCG
      and then decreases gradually. It is not clear how eCG regulates luteal androgen
      and oestrogen production. In the present study, the steady-state mRNA expression
      of 3beta-hydroxysteroid dehydrogenase (3beta-HSD), cytochrome P450 17alpha
      hydroxylase/17,20-lyase (P450(17alpha)) and cytochrome P450 aromatase (P450arom)
      in primary corpora lutea before, during and after eCG secretion was determined by
      northern blotting. Expression of 3beta-HSD was similar at all the stages
      examined. Cytochrome P450(17alpha) expression increased at the onset of eCG
      secretion, decreased between days 42 and 46 of gestation and was constant for the
      remaining period of eCG secretion. Cytochrome P450arom expression was highest
      before and after eCG secretion and lowest during periods of peak eCG secretion.
      The differential expression of P45017alpha and P450arom indicates that production
      of luteal androgen and oestrogen is regulated by P450(17alpha), activity. The
      effect of eCG on luteal steroidogenic enzyme mRNA expression appears to be stage
      specific.

PMID- 20681179
TI  - Equine trophoblast as an immunological target.
AB  - A cytotoxic T-lymphocyte assay was used to determine whether equine chorionic
      girdle cells are susceptible to lysis by CD8+ cytotoxic T cells primed in vitro
      against allogeneic lymphocytes. Classical cytotoxic T-lymphocyte activity against
      fresh or cultured trophoblast targets was demonstrated using peripheral blood
      lymphocytes from nonpregnant mares. Lysis of allogeneic (horse) and xenogeneic
      (donkey) lymphocyte targets was used as a control for trophoblast lysis. The
      major histocompatibility complex (MHC) class I specificity of the cytotoxic T
      lymphocyte reactions was determined using panels of MHC-typed target cells. The
      results of the present study demonstrate that the MHC class I antigens expressed
      on equine chorionic girdle cells are functional proteins, which can serve as
      targets for CD8+ allospecific cytotoxic T lymphocytes. Furthermore, these
      findings indicate strongly that, at least in the in vitro assay used, MHC class I
      positive chorionic girdle cells do not display any mechanisms that can protect
      them from lysis by activated maternal T cells.

PMID- 20681180
TI  - Immunization with stallion lymphocytes for treatment of recurrent spontaneous
      abortion in thoroughbred mares.
AB  - The incidence of recurrent spontaneous abortion within the human population in
      the Western world is low (2-5%) but significant, and a proportion of these
      pregnancy losses are thought to have an underlying immunological cause.
      Immunization of women who have a history of recurrent spontaneous abortion with
      lymphocytes isolated from their husband or a third party donor is one of several
      forms of immunotherapy used to treat the problem. Early pregnancy loss in
      Thoroughbred mares is also significant and, as in women, a small number of mares
      undergo repeated pregnancy losses. Two trials have been performed in which
      Thoroughbred mares suffering from recurrent spontaneous abortion before day 150
      of gestation were immunized with lymphocytes isolated from the mating stallion or
      from an unrelated stallion. The first trial, which was conducted without control
      mares, resulted in a very high live birth rate (97%) for the mares (n=24)
      treated. Therefore, a second controlled double-blinded trial was established in
      which randomly selected mares (n=17) were treated with stallion (heterologous)
      lymphocytes and control mares (n=13) were injected with their own (autologous)
      lymphocytes. The live birth rates after these treatments were 88 and 77%,
      respectively. Thus, immunization with stallion lymphocytes had no effect on the
      incidence of abortion in mares suffering from recurrent spontaneous abortion.

PMID- 20681181
TI  - Evaluation of equine fetal growth from day 100 of gestation to parturition by
      ultrasonography.
AB  - Transrectal and transabdominal ultrasonography were performed on normal pregnant
      mares (n=10) at 2 week intervals from day 100 of gestation to parturition to
      evaluate fetal growth. Several fetal anatomical regions (head, eye, aorta,
      abdomen, rib, gonad, kidney and femur) were imaged and measured using
      standardized scan plans. The results of these analyses indicate that all of the
      biometric parameters correlate strongly with the day of gestation. Growth charts
      were developed, which demonstrate that the following variables have linear
      relationships with the day of gestation on which they were measured: aortic
      systolic diameter, biparietal diameter, approximate eye volume, femur length and
      kidney cross-sectional area. The linear regression equation across days was
      developed for aortic, systolic and biparietal diameter, approximate eye volume,
      femur length and kidney cross-sectional area, thus allowing assessment of normal
      equine fetal development after day 100 of gestation. This non-invasive method can
      be used to estimate fetal age if mating or ovulation dates are unknown, provided
      the fetus is developing normally. The use of transrectal and transabdominal
      ultrasonography, as well as different probe frequencies (5.0 or 3.5 MHz), to
      measure different biometric parameters during gestation is reported.

PMID- 20681182
TI  - Progesterone, oestrogen and glucocorticoid receptors in the uterus and mammary
      glands of mares from mid- to late gestation.
AB  - Progesterone, oestrogen and glucocorticoid receptor concentrations in the uterus
      and mammary glands of pregnant mares during mid- to late gestation (from day 150
      of gestation to term) were measured by binding assays to investigate the hormonal
      mechanisms involved in pregnancy maintenance and lactation. Uterine progesterone
      receptor concentrations did not increase significantly with increasing
      gestational age (from 67.8 +/- 13.7 to 126.1 +/- 48.7fmol mg(-1) protein),
      whereas oestrogen receptor concentrations were significantly higher in pregnant
      mares (271.7 +/- 28.9 fmol mg(-1) protein) than in non-pregnant control mares
      (54.9 +/- 8.1 fmol mg(-1) protein; P < 0.05). There was no correlation between
      progesterone and oestrogen receptor concentrations, and plasma progesterone and
      oestrone sulphate concentrations, respectively. In contrast, mammary gland
      progesterone and oestrogen receptor concentrations decreased significantly with
      gestational age (from 139.7 +/- 34.6 to 66.7 +/- 22.0 fmol mg(-1) protein and
      225.2 +/- 13.3 to 87.6 +/- 14.4 fmol mg(-1) protein, respectively; P < 0.05). The
      dissociation constant (Kd value) of 16alpha-ethyl-21-hydroxy-19-nor-4-pregnene
      3,20-dione (ORG2058) for progesterone receptors was 22 nmol l(-1). 5alpha
      pregnane-3,20-dione (5alpha-DHP) had a high affinity for progesterone receptors,
      which was similar to that of progesterone, whereas other equine progestagens and
      11-[4-(dimethylamino)phenyl]-17-hydroxy-17(1-propynyl)estra-4,9-diene-3-one
      (RU486) did not bind to progesterone receptors. Oestradiol bound the oestrogen
      receptors with a Kd value of 0.9 nmol l(-1), which was 10 times more potent than
      that of 3-hydroxy-1,3,5(10),7-oestratetraen-17-one (equilin). The concentration
      of glucocorticoid receptors (Kd value = 1.3 nmol l(-1)) was constant between the
      tissues and reproductive stages. In the present study, striking differences were
      observed between progesterone receptor expression in the uterus and the mammary
      glands during pregnancy, probably due to tissue-specific variations in 5alpha-DHP
      activity. This finding indicates that 5alpha-DHP has an important physiological
      role in equine gestation.

PMID- 20681183
TI  - Effect of increased daylight during late pregnancy on the reproductive
      performance of mares after parturition.
AB  - The aim of the present study was to determine the effect of prolonged photoperiod
      during late pregnancy on subsequent ovarian activity and fertility in mares.
      Pregnant mares (n=13) due to give birth in January and February were stimulated
      by a fixed photoperiod (16 h light: 8 h dark) from 15 November (during the last 2
      3 months of gestation) until up to 1 month after parturition. A control group of
      mares (n=9) due to give birth at the same time were kept in the same stable and
      management regimen, but under natural light conditions. Light-treated mares
      ovulated during foal oestrus approximately 3 days earlier than did the control
      mares (P < 0.05). The incidence of winter ovarian inactivity in foaling mares was
      7.6% in the treatment group and 33% in the control mares. The processes of
      involution and uterine fluid expulsion were similar in both groups. The final
      pregnancy rate was high in both the experimental and control groups, being 92 and
      89%, respectively. However, the duration of the open period (period from
      parturition to next pregnancy) was significantly shorter in the mares that
      received the light treatment compared with the untreated control mares.

PMID- 20681184
TI  - The effects of oxytocin and progestagens on myometrial contractility in vitro
      during equine pregnancy.
AB  - Progesterone or progestagens are thought to maintain myometrial quiescence in
      pregnant mares, although this has not been proven. In the present study, the
      contractility of the equine myometrium was tested in vitro using samples
      collected from pregnant mares (n=33) between day 68 and day 340 of gestation.
      Myometrial samples were equilibrated in aerated Krebs buffer and subjected to one
      or more of these treatments: (i) oxytocin only; (ii) initial oxytocin treatment
      followed by combined oxytocin and progesterone or another progestagen; and (iii)
      initial oxytocin treatment followed by Krebs buffer followed by progestagen; (iv)
      initial progesterone treatment followed by progesterone and oxytocin. Spontaneous
      contractile activity did not occur within 180 min. The oxytocin-only treatment
      resulted in a significant (P < 0.01) dose-dependent increase in myometrial
      resting tension. Myometrial contraction amplitude and frequency tended to
      increase and decrease, respectively, with increasing concentrations of oxytocin,
      but the effect was not significant. However, there was no correlation between the
      amplitude and frequency of myometrial contractions and gestational age. Treatment
      with progestagens did not alter the amplitude or frequency of oxytocin-stimulated
      myometrial contractions, regardless of whether progestagens were given with
      oxytocin (treatment (ii)), without oxytocin (treatment (iii)) or before oxytocin
      treatment (treatment (iv)). These data support the results of in vivo studies on
      the stimulatory effect of oxytocin on equine myometrium and indicate that
      progestagens are ineffective at controlling myometrial contractility in vitro. It
      is hypothesized that other hormones may be involved in this process.

PMID- 20681185
TI  - Developmental changes in blood pressure and the renin-angiotensin system in pony
      fetuses during the second half of gestation.
AB  - Blood pressure, heart rate and the plasma concentrations of cortisol and
      components of the renin-angiotensin system were measured in chronically
      catheterized Pony mares (n=15) and their fetuses during the second half of
      gestation (day 153-336 of gestation; term is normally between day 320 and day 340
      of gestation). Fetal blood pressure increased towards term with the prepartum
      surge in plasma cortisol concentration, and there was a correlation between fetal
      blood pressure and both gestational age (r = 0.88, P < 0.0005) and plasma
      cortisol concentration (r = 0.88, P < 0.0005). Plasma concentrations of
      angiotensin-converting enzyme (ACE) and angiotensinogen increased towards term in
      the fetus; plasma ACE correlated with gestational age (r = 0.83, P < 0.0005),
      plasma cortisol (r = 0.76, P < 0.005) and blood pressure (r = 0.84, P < 0.0005),
      whereas plasma concentrations of angiotensinogen correlated with gestational age
      only (r = 0.80, P <0.0005). Fetal heart rate was correlated inversely with
      gestational age (r = -0.67, P < 0.05), plasma ACE concentration (r = -0.58, P <
      0.05) and plasma angiotensinogen concentration (r = -0.69, P < 0.05). There was a
      positive correlation between plasma angiotensin II and renin concentrations in
      the fetuses (r = 0.81, P < 0.05). No gestational changes in plasma angiotensin II
      or renin concentrations were observed in either the mares or fetuses. Maternal
      blood pressure, heart rate, plasma ACE and plasma angiotensinogen concentrations
      also did not change over the period of study. Therefore, in Pony fetuses,
      maturational changes in the activity of the renin-angiotensin system occur
      towards term and coincide with the prepartum cortisol surge. These changes in the
      fetal renin-angiotensin system may be responsible, at least in part, for the
      observed ontogenic increase in fetal blood pressure.

PMID- 20681186
TI  - Maternal influence on pre- and postnatal growth of foals born after embryo
      transfer.
AB  - In the present study the growth and development of three pairs of matching gender
      foals from birth to maturity were compared. One Polish Pony embryo of each pair
      was transferred from a donor mare (mass 387-400 kg) to a much larger heavy type
      recipient mare (mass 561-780 kg). The other embryo of each pair underwent normal
      gestation (control). The transferred and control horses were examined at 9 and 13
      years of age, and X-ray pictures were taken of their front legs to measure the
      length of the bones. On the basis of the results of this study, it is concluded
      that the processes of growth and development in transferred foals born to heavy
      type recipient mares can be divided into three phases. During the first fetal
      stage, body weight gain and growth are faster in transferred foals than in
      control foals. In the second phase, which comprises the suckling period, the
      transferred foals put on weight faster than control foals, but the growth rate is
      slower than during the first phase. In the third phase, after weaning, both body
      weight gain and growth rate are comparable to those of control foals.

PMID- 20681187
TI  - Response of newborn foals with thyroid musculoskeletal disease to
      adrenocorticotrophic hormone (ACTH).
AB  - Fetal maturation and equine parturition are not understood fully, although the
      adrenal and thyroid glands are thought to have regulatory roles. Thyroidectomized
      equine fetuses undergo prolonged gestation, and spontaneous diseases such as
      thyroid musculoskeletal disease and gestational fescue endophyte exposure are
      also associated with delayed parturition. Thyroid musculoskeletal disease is
      characterized by: histologically hyperplastic thyroid glands, chondro-osseous
      dysplasia and dysgenesis, angular limb deformity, low resting thyroxine and
      triiodothyronine concentrations, and lack of response to thyroid stimulating
      hormone. There are also similarities between foals born to mares grazing fescue
      grass infected with endophytes and foals with thyroid musculoskeletal disease (TH
      MSD foals). It is thought that there may be an endocrine basis for the prolonged
      gestation observed in these disease states. The aim of the present study was to
      determine the endocrine competence of the adrenal gland in TH-MSD foals.
      Adrenocorticotrophic hormone (ACTH) response tests were used to compare the
      functional ability of the neonatal adrenal gland in healthy foals and TH-MSD
      foals. Basal thyroxine concentrations were significantly different between groups
      (P < 0.02): the thyroxine concentrations were lower in TH-MSD foals. After ACTH
      administration there was a significant effect of time (P < or = 0.001), but not
      treatment, on cortisol concentrations in foals. Thyroid hormone deficiency in TH
      MSD foals did not significantly affect adrenal cortical secretion after ACTH
      administration. This finding indicates that thyroid function may play a major
      role in the timing of parturition either directly or indirectly via a mechanism
      other than by influencing adrenal responsiveness to ACTH.

PMID- 20681188
TI  - Gastrointestinal and endocrine function during 'foal heat diarrhoea' in healthy
      foals.
AB  - Gastrointestinal function was assessed in normal foals before, during and after
      the onset of 'foal heat diarrhoea' by haematological, biochemical,
      microbiological and parasitological methods, and by a combined lactose tolerance
      breath hydrogen excretion test. Warmblood mares (n=11) and their foals were used.
      The foals were assessed according to a standard protocol after birth and at
      regular intervals thereafter. All except one of the foals suffered from diarrhoea
      that started between day 8 and day 12 after birth, which lasted for 1-4 days.
      Rotavirus was detected in the faeces of five foals, but there was no association
      with the occurrence of diarrhoea. A significant increase in aldosterone
      concentration compared with that at days 6 and 18 was observed in five foals on
      the second day of diarrhoea. There were no differences between age groups in
      plasma glucose concentrations after lactose administration. Peak breath hydrogen
      excretion after lactose administration ranged from 17 to 232 p.p.m., and
      increased with age of foal. There was no decrease in lactose absorption or
      increase in breath hydrogen excretion in foals suffering from diarrhoea.

PMID- 20681189
TI  - Effect of transport on the intensity of stress reactions in mares and foals.
AB  - The aim of this study was to determine the effect of transportation on the
      behaviour and stress responses of the sympatho-adrenal and hypothalamo-pituitary
      adrenal systems in mares and their foals by measuring the peripheral plasma
      concentrations of adrenaline, noradrenaline and cortisol. Control blood samples
      were taken from mares and their foals (n=5 pairs) on day 8 after parturition to
      establish whether blood sampling caused any changes in adrenaline, noradrenaline
      or cortisol concentrations in blood plasma. The experiment was conducted during
      foal oestrus (on day 9 after parturition). Adrenaline and noradrenaline
      concentrations increased in the blood plasma of mares after only 10 min
      transportation and the increased concentrations were maintained until 30 min
      after transportation. The adrenaline and noradrenaline concentrations in foal
      blood plasma increased after 10 min transportation and decreased rapidly to basal
      concentrations. Cortisol concentrations in the blood plasma of mares reached a
      peak after 60 min transportation. Peak cortisol concentrations in foal blood
      plasma were attained after transport was completed. The results of the present
      study indicate that transportation during foal oestrus is a stronger stress
      causing factor for mares than for their foals.

PMID- 20681190
TI  - Equine reproduction VII. Summing up.

PMID- 20681191
TI  - [Heinrich Hoffmann's Der Struwwelpeter (1845/1859): a parody on the romantic cult
      of childhood].
AB  - This article analyzes the cultural dynamics of the construction and
      deconstruction of childhood images, by means of a case study of Heinrich
      Hoffmann's classic picture book, Der Struwwelpeter (1845/1859). Childhood images
      are the joint product of sciences (especially anthropology, pedagogy and
      developmental psychology) and arts (especially painting, photography and
      (children's) literature). These images are historically variable, because
      childhood is the permanent target of idealization and demystification. This
      article interprets Der Struwwelpeter as a demystication of Romantic idealizations
      of childhood as propounded by Romantic Naturphilosophie and, more specifically,
      the pedagogy of Friedrich Frobel (1772-1852). In my view, this picture book
      satirizes the developmentalism and the pastoryl idyll which informed the Romantic
      image of childhood, through its verbal and visual components. As I argue at
      length, this satire directly bears upon leading scientific and political
      controversies of Hoffmann's time.

PMID- 20681192
TI  - [The unicorn and the pharmacists. Early modern views on the presumed anti-toxic
      effects of unicorn horn].
AB  - Around 1600, the age-old belief in the anti-toxic effect of unicorn horn began to
      be called into question. This is evidenced by the views of two well-known French
      pharmaceutic authorities whose publications are discussed in this paper: the
      surgeon Ambroise Pare (1510-1590), court physician to four French kings, and the
      Montpellier pharmacist Laurent Catelan (1568-1647), who owned a famous cabinet de
      curiosites. Although Pare had to accept, however reluctantly, the existence of
      the unicorn (since it is mentioned in the Bible), he vehemently denied the
      supposed medicinal effect of unicorn products. He defended his position by an
      appeal to ancient and contemporary authorities, by rational argumentation, and by
      experiment. Pare's arguments failed to convince Catelan, who adhered to an
      alternative, so-called spagyric, medical theory of neoplatonic inspiration, as
      propagated by Paracelsus and Ficino. Catelan remained convinced of the efficacity
      of unicorn horn, which in his view could drain the human body from any poisonous
      substance. The medical establishment being reluctant to give up a rewarding
      source of income,'unicorn' remained much in demand as a prescription.

PMID- 20681193
TI  - [Challenges and advances in the care of injuries in the Republic of Serbia].
AB  - There are many problems that trauma care system in Serbia is facing today. Few of
      them are: 1) Lack of categorization of trauma centers; 2) Diversity in managing
      of trauma patients among institutions; 3) There is no trauma management training,
      4) Inappropriate cooperation between pre hospital trauma care and hospital trauma
      care; 5) There is no standard in managing of trauma patients as well as
      procedures. To improve trauma care quality throughout the country we must learn
      from the experiences of other countries. The aim of this paper was to report
      representative data about organization, management, stuff and equipment of
      ambulance and emergency services in Serbia. We analyzed 12 out of 138 parameters
      we obtained from the relevant institutions.

PMID- 20681194
TI  - [Damage control surgery in abdominal trauma].
AB  - The damage control laparotomy is an advancement in the management of massively
      injured trauma patients. Massive liver injuries, pelvic trauma and some
      retroperitoneal injuries are some of the indications for this approach. The
      damage control laparotomy is the phased approach to severe abdominal injury that
      might best be described with the acronym STIR (Staged Trauma Injury Repair). The
      initial procedure requires rapid abdominal exploration with hemorrhage and
      contamination control, using suture repair combined with abdominal packing.
      Temporary abdominal wall closure without tension is recommended. After abrevated
      initial surgical procedure, the patient is transferred to the intensive care unit
      where continued resuscitation is performed. Careful replacement of blood and
      blood products along with correction of hypothermia, acidosis and optimalization
      of oxygen transport represents a critical phase in this management approach. Once
      the coagulation profile has normalized, planned re-intervention, with repeat
      abdominal exploration to remove the packs and perform definitive surgical repair
      and reconstruction takes place. When applied judiciously, the damage control
      laparotomy with the staged abdominal repair and reconstruction for severe trauma
      is associated with an improved outcome in the selected group of patients.

PMID- 20681195
TI  - [Unstable fractures of the pelvis treated by Ilizarov external fixation device].
AB  - We reviewed seven patients with an unstable fracture of the pelvic ring who had
      been treated with a Ilizarov external fixation device after a mean follow-up of
      5.5 years. There were four "open-book" injuries (type B according to Tile) and
      three rotationally and vertically unstable injuries (type C according to Tile).
      In all patients union of fracture site had been achieved after a mean period of
      65 days in patients with type B injuries and 98 days in patients with type C
      injuries. In the four patients with an "open-book" injury the symphyseal
      diastasis was partially reduced from 46 mm to 13 24mm to 13mm. The radiological
      result was excellent in one patient, good in one and poor in two patients. The
      functional outcome was rated as excellent in three patients and good in one
      patient. In patients with type C injury vertical displacement was partially
      reduced from 21mm to 12mm. The patients in this group had excellent, good and
      poor radiological result, respectively. The functional outcome was excellent in
      two cases and good in one case. General surgical complications were not seen.
      Infection at the pin sites was seen in six patients. In our study unsatisfactory
      or poor functional result was not registrated due to construction characteristics
      of Ilizarov device. Because of this characteristics there were no residual
      vertical displacement more then 8 mm.

PMID- 20681196
TI  - [Fixation of the tuberculum in multifragment fractures of the proximal humerus
      treated with hemiarthroplasty].
AB  - Hemiarthroplasty is an effective treatment for multifragmentary fractures of the
      proximal humerus. Purpose of this study was to compare 2 different methods of
      tuberosity dislocations,which is one of the primary reasons for successful
      posttraumatic arthroplasty. Between 2006 and 2008, 29 patients with
      multifragmentary fractures of the proximal humerus underwent hemiarthroplasty of
      the shoulder. Mean gae was 69y., while mean postoperative follow up was 27
      months. We evaluated two different techiques of tuberosity fixation after
      anatomic reattachment on humeri: (A) intertuberosity suture stabilization around
      the prothesis, and their suture to the humeri and (B) direct intertuberosity
      suture and their suture to the humeri Postoperartive Constant score averaged 71
      points. Reason for failure of the operative treatment was primary due to the
      postoperative tuberosity migration It was noted in all patients of group 2 and in
      2 patients of group 1. Intertuberosity stabilization using sutures arpund the
      prothesis and tuberosity fixation to the humeri was proofed to be optimal method,
      because it decreased strain and mobility of tuberosities, maximize stability of
      the hemiarthroplasty and facilitate postoperative rehabilitation.

PMID- 20681197
TI  - [Intramedullary fixation and proximal femoral fractures: diversity in use through
      case reports].
AB  - Proximal femoral fractures, including intertrochanetric and subtrochanteric with
      diaphiseal propagation represent a significant challenge in orthopedic surgery,
      especially in older population. Retrospective analysis of patients, after the
      application of "Bi Nail (Bioimpianti Inc.) intramedullary nail for fractures and
      pathological conditions of proximal femur, was done at the Department of Adult
      Orthopedics, Institute of Orthopedic surgery Banjica, during the three year
      period. We present patients with complex fractures and pathological conditions
      (metastasis and pseudoarthrosis) of proximal femur; most of the fractures were
      result of effects of low energy, and the most common pathological fracture is due
      to metastasis of breast cancer. The analysis included the technical
      characteristics and duration of surgery, intraoperative and postoperative
      complications as well as the coalescence time of fracture healing and
      postoperative quality of life after rehabilitation. We believe that the described
      surgical method, although technically demanding, with a variable length duration
      of surgery and treatment of high risk elderly patients, provides stable fracture
      fixation with early rehabilitation to improve the quality of life.

PMID- 20681198
TI  - [Early complications in elderly patients opereted because of the fracture of the
      femoral neck].
AB  - Fractures of the femoral neck are the most common with the older population, and
      in this population are dominantly made by the forces of low strength intensity.
      AIM: To show early complications ensued during the first 6 weeks after the
      surgical treatment of the older patients with fractures of the femoral neck.
      MATERIALS AND METHOD: 315 hospitalised patients are included within the
      retrospective analysis who are operated because of the fracture of the femoral
      neck in KBC Bezanijska Kosa in Belgrade, in the period 2007-2010. RESULTS: Early
      complications noted during the first 6 weeks after the surgery were: death of the
      patient 17 (5.3%), dislocation of the endoprosthesis 12 (3.8%), wound infection 8
      (2.5%), pulmonary embolism 1 (0.3%), deep-vein thrombosis 6 (1.9%), lesion n.
      peroneusa 4 (1.2%), paraplegia 1 (0.3%), decubital wounds of sacral region 15
      (4.8%). CONCLUSION: Aloplastic surgery of dislocated fractures of the femoral
      neck with the older population enables relatively fast mobilisation of the
      patients, early rehabilitation of the patients with acceptable number of the
      early complications.

PMID- 20681199
TI  - [Minimal-incision total hip arthoplasty: complications].
AB  - Minimally invasive hip surgery techniques have been proposed as an alternative to
      conventional soft tissue exposure total hip arthroplasty. Purposed advantages of
      the technique included less blood loss, faster recovery, shoter stay in hospital
      and better cosmetical result. During the years good results have been presented
      by many authors, and serious complications have been found only in a few
      articles. But, some papers reported a catastrofic complications of the MIS
      procedures. Our intention is to present complication which had occured in our
      experience with MIS total hip replacement. Retrospective study involved 215
      patients (230 hips). All patients, of mean age 55.7 years, obtained fiber metal
      midcoated or fiber metal taper femoral stem and identical fiber metal coated
      acetabular shell with polyethylene or ceramic insert. The goal of the study was
      to evaluate intraoperative and early postoperative complications: bone fractures
      and/or implant, blood loss, dislocations, prolonged bleeding, loss of component
      position in 6 week postop. period, infections, and thromboembolism. The
      complications we had may occure with any type of operating technique. The purpose
      of the study was not either to condone or condemn MIS techniques but to shaw the
      complications that had occurred in our experience.

PMID- 20681200
TI  - [Diagnosis and treatment of Paget disease of the spinal vertebrae].
AB  - Paget disease, localized only on thoracic spine is extremly rare. It is a huge
      diagnostic problem and an equally big therapy challenge. Course of this disease
      is slow, it chronically worsens, thus demanding differentiation of various
      conditions, along with orthopaedic, neurological, radiographic and endocrine
      evaluation. Paget disease is followed by back pain, progressive weakening of legs
      and sphincter functions, due to pathological spine fractures and spinal stenosis.
      The treatment is surgical, in form of decompression and applying biphosphonates.
      Three patients are presented, all with worsening back pain which lasted several
      months. Hyperthonia and hyperreflexion of lower extremities were developed
      significantly. Over the course of time, neurological deficite got worse, almost
      to the point of spastic parapalegia. All of the patients were male, 50 to 68
      years old. They had higher values of alcaline phosphatase and serum calcium than
      usual. In all cases, bone scintigraphy was positive where the lesion of thoracic
      spine existed. Biopsy suggested hyperparathyroidism, but, as it turned out,
      wrongly. After surgical treatment, neurological improvement was noticed on all
      three patients. In case of two, recidives occurred after three and five years
      respectively, so surgical reinterventions were made. These recidives are
      consequences of Paget disease progression. Aside from surgical treatment, they
      were treated by encrinologist. Remission of the disease lasted for seven and
      twelve years, respectively. Third patient had his condition recognized almost two
      years after first reception, and, due to big changes on vertebral body and
      paraplegia, posterior and anterior decompression of spinal canal and
      stabilization were done simultaneously. Biopsy confirmed Paget disease. During
      the postoperative course, nearly complete neurological improvement occured almost
      instantly. Only moments after hospital release, twenty four days after the
      operation, patient got sick in the hall. Unfortunately, he passed away due to
      massive lung embolism, even though he recieved adequate thromboembolic
      prophylaxion. Monoostotic form of Paget disease localized on vertebral body must
      be taken and considered seriously, especially when the patients suffer from
      progressive evolution of neurological deficite, followed by adequate biochemical
      blood and urine analysis, as well as radiographic signs of pathological fracture
      or invasive vertebral process. Surgical treatment can lead to significant
      improvement of clinical findings, but due to recidive, biphosphonate treatment is
      recommended.

PMID- 20681201
TI  - [Treatment of occipitocervical instability by SUMMIT].
AB  - The occipitocervical junction with its complex anatomy and biomechanics
      represents unique anatomical structure difficult for operative treatment.
      Biomechanics forces in this region need to be resisted with rigid metallic
      construction to facilitate bone fusion. Surgeon must be careful about close
      relations of the bone, vascular and neurologic structures and must have good
      skills and knowledge to avoid serious complications during operations. Before
      2004 for instability treatment in this region of spine wires and pin construction
      for fixation of bone grafts were used. In our Institute rod constructions with
      screws have been used to get more rigid construction since 2004. In this paper we
      will present our early results in occipitocervical instability treatment by
      SUMMIT instrumentation.

PMID- 20681202
TI  - Osteoblastoma of the spine.
AB  - A retrograde analysis of 64 spinal osteoblastomas treated by surgery during the
      period 1963 - 2005 has been made. Spinal osteoblastomas were presented in 36% of
      all skeletal localizations. There were 44 male and 20 female patients. The
      average age of patients at the time of surgery was 14 years. Localizations of the
      osteoblastomas were cervical spine in 8 cases, dorsal spine in 16 cases, lumbar
      spine in 38 cases and sacrum in 2 cases. Osteoblastomas predominantly involved
      posterolateral vertebral elements, although in two cases a primary localization
      was in vertebral bodies. Neurological deficits were relatively moderate, but a
      paraplegia occurred in six patients. Scoliosis was present in 50% of cases, and
      their respective prognosis depended on the duration of the painful syndrome as
      well as on the age when the disease had set up. According to Enneking
      classification 30 patients were evaluated as stage 2 and 34 othe-rs as stage 3.
      Relapses were noticed in 8 (12.5%) pati-ents. Clearly delineated lesions were
      treated by an intralesional procedure, but aggressive ones were treated by a
      marginal surgery followed by additional radiotherapy (6 patients). The average
      follow-up period was 13 years.

PMID- 20681203
TI  - Are the additional grafts necessary?
AB  - The goals of surgery for spinal deformity are to correct or improve the deformity
      to get a stable, balanced and fused spine. The long-term success of any procedure
      for scoliosis depends on a solid arthrodesis. Getting fusion of the instrumented
      segment with the aid of copious autogenous iliac graft has been the most
      important goal of treatment. However, harvesting copious graft from teenage iliac
      bone has its limitation in the quantity of graft, surgical time, and other
      complications of graft sites. Bone substitute is a promising concept, but there
      is not ideal bone substitute with all the characteristics of an autogenous bone
      graft. Several alternative graft materials like tricalcium phosphate,
      hydroxyapatite, and demineralized bone matrix have osteoinductive properties.
      Bone morphogenic protein has osteoconductive properties. The limitations with
      bone substitutes are osteoinduction and osteoconduction properties,
      sterilization, chances of transmitting infective disease and cost. We consider
      that the introduction of segmental spinal instrumentation which enables strong
      and firm correction and fixation of the scoliotic deformity has enabled getting
      fusion with less graft. We can obtain that quantity of graft after laminae and
      spinous process decortication. This retrospective study has been done in our
      hospital from January 2002 to December 2004. A total of 188 patients underwent
      posterior corrections for adolescent idiopathic scoliosis using segmental
      fixation by Moss-Miami. No autogenous iliac crest graft was taken or graft
      substitutes. After meticulous decortication and destruction of facet joints, we
      used local graft taken from spinous process and laminae. All patients had minimum
      thirty months follow-up. We have excellent results. Out of these 188 patients,
      177 patients have fused spine, no implant failure, no pain, no infection and no
      loss of correction. Eleven (5.8%) patients underwent re-operation; four among
      them because of infection, three for symptomatic implants and four due to
      pseudarthrosis. We consider that the use of local harvesting graft is enough for
      getting good spondylodesis.

PMID- 20681204
TI  - [Congenital club foot].
AB  - Congenital club foot is the most frequent foot deformity. It occurs in 1% of
      newborns, two times more frequently in boys, with family inheritance.
      Patoanatomicaly, entity consists of bone deformities, articular malpositions and
      soft tissues retraction. All these produce adduction of the forefoot and varus
      and equinovarus of the hindfoot. Lateral side of the foot is convex and medial
      side is concave. Forefoot is in adduction and plantar flexion in relation to the
      hindfoot. The heel is rotated medialy which induces varus and eqinus of the foot.
      The aim of the treatment is to establish anatomically normal foot, painless, with
      moderate movements, which is suitable for normal shoes. At the beginning
      treatment is nonsurgical. If nonsurgical treatment fails further step should be
      surgical treatment. The success of treatment of congenital clubfoot depends on
      the time of diagnosis and treatment beginning.

PMID- 20681205
TI  - [Current trends in surgical treatment of radial nerve injuries associated with
      injuries of the humerus].
AB  - Radial nerve is the most common injured peripheral nerve after bone and wrist
      injuries in human body. Radial nerve can be injured by force causing fracture of
      the humeral shaft, due to compound fracture of the bone or by direct injury with
      small fragments of the bone. This happen in of cases and in remaining caseswas
      caused by manipulation during the treatment of the fracture of the humeral shaft.
      Because of the possibility of spontaneous recovery, indication and timing of
      surgical treatment of the radial nerve still remain controversial. There is
      contradictory approach in the treatment of the injured radial nerve. In a period
      betwen 1979 and 2005 year we have operated 193 patients with injury of radial
      nerve. Among them, 97 (50.2%) have had combined injury of the humeral shaft or
      proximal part of radius. Rest of injuries of the radial nerve were associated
      with manipulation during treatment. Surgical treatment has been performed in a
      period between three and four months after neurological deficit. Analysing our
      result regarding recovery of the motor function we have used combination of
      gradation including British Medical Council Score and modified Highet Scale to
      obtain satisfactory analysis of useful functional recovery of motor function
      after surgical procedure. We have classified results as bad M O-2 for all muscles
      innervated by the radial nerve; satisfactory M3, for extensors of the wrist and
      fingers and M O-2 for abductor of the thumb, good M 4-5 extensors of the wrist
      and fingers and M3 for abductor of the thumb, and excellent M 4-5 for all
      muscles.

PMID- 20681206
TI  - Unusual position of bone tunnels in failed ACL reconstruction.
AB  - INTRODUCTION: Surgery of ACL deficient knees is very frequent nowadays due to
      advanced surgical techniques, sophisticated implants and large number of
      surgeons. Therefore, the number of revisions for various reasons is growing up.
      There are several well known reasons for failed surgery This paper reported a
      case of revision surgery in a patient with previously done and failed
      reconstruction of ACL. CASE OUTLINE: Reviewing the clinical findings and X rays
      we found out peculiar position of the transplant and tunnels as a cause of the
      failure. We haven't found such complication reported in literature therefore we
      decided to report the case. CONCLUSION: Variety of implants and instruments can
      ease the surgery but basic anatomical knowledge of position and relations of the
      knee ligaments are essential for good surgical outcome.

PMID- 20681207
TI  - [Postoperative use of nonsteroidal anti-inflammatory agents in orthopedic
      surgery].
AB  - Nonsteroidal antiinflamatory drugs (NSAIDs) lead to satisfactory acute and
      chronic pain relief. Besides that, they exert potent antiinflamatory effect.
      Their analgesic potency is dose related and limited. Orthopedic patients are
      often on these medications preoperatively and experience opioid-sparing effect in
      the postoperative period. Chronic NSAIDs use is related to higher rate of
      sistemic adverse effects, but even short time exposure in the postoperative
      period is not risk-free. Although Coxibs reduce GIT bleeding incidence due to
      prolonged use of NSAIDs, there has to be judicious decision considering their
      cardiovascular adverse effects. There is evidence that NSAIDs producing moderate,
      dose-dependent increased bleeding time within normal values. High risk of
      bleeding have patients with established coagulopathy, alcohol abuse and on
      anticoagulant treatment. There is no strong evidence on influence of NSAIDs on
      bone growth. Nevertheless, there is evidence that NSAIDs do prevent heterotropic
      ossification. Prostaglandins are vital contributors for maintainig tissue
      homeostasis and NSAIDs use can lead to many unwanted effects. Those adverse
      effect are more common with prolonged exposure, are dose-related and risks have
      to be carefully and individually assesed in the postoperative pain management.

PMID- 20681208
TI  - [Scoring system for evaluation of clinical outcome of severe injuries in
      patients].
AB  - A trauma-scoring system converts the severity of injury into a number, so helping
      clinicians to define patient's condition. Aim of our investigation was assessment
      of scoring systems in clinical outcome of patients with severe traumatic injury,
      as well as ISS, AIS, APACHE II and SOFA score were counted. Mean age of
      traumatized patients was 35 yrs, predominantly males. Based on results of our
      investigation we concluded that ISS, APACHE II and SOFA score adequately can be
      used for predicting clinical outcome of severe traumatized patients.

PMID- 20681209
TI  - [Liver injuries--personal experience with treatment].
AB  - BACKGROUND: Trauma is one of todays most serious and expensive health care
      problems, and it is the most common cause of mortality in young population. Non
      operative tretment is standard strategi for menagment of blunt liver injuries in
      hemodynamically stable patiens in last decade. METHODS: Retrospective study
      included patiens with liver trauma, admitted in the period december 1995 -
      december 2005, in total 476. RESULTS: 392 of 476 patients presenting with liver
      trauma had blunt and only 84 had penetrating injury. Isolated liver injury was
      identified in 27.5% and 72.5% had associated injuries. Average ISS value was
      24.06 (SD = 14.26).During the operation liver injury in patients was classified
      according to Moor. In 2% critical patients, due to hemodynamic unstability we
      performed "damage control surgery". Out of 476 patients 8.7% were successfully
      managet, 6.1% died as "mors in tabula" or during first 24 hours and 6.9% died
      during hospitalization. CONCLUSION: Higher proportion of nonoopertively treated
      is among patients with ISS less thanand those with injuries grade I end II.

PMID- 20681210
TI  - [Blood replacement in severely injured patients].
AB  - Haemorrhage remains a leading cause of early death in injured and application of
      concentrated RBC transfusion in the treatment of multiple injuries is the basis
      and potential component of saving lives. The aim of this study was to analyze the
      received amount reimbursed blood in patients with severe trauma, depending on the
      outcome, severity and mechanism of injury. Collected data on gender, age and age
      as the mechanism of injury, amount of blood recovered intraoperatively and during
      the first six days of hospitalization, which were analyzed according to outcome
      of treatment, ISS, AIS, and APACHE II score. Results showed that patients with
      lethal outcome received a larger amount of blood, there is a statistically
      significant correlation with ISS and AIS score for extremity injuries, and that
      larger amount of blood received patients injured in the traffic accidents, as
      pedestrians and motorcycle riders/bike, and there is no correlation with APACHE
      II score. Based on the importance of this topic for further research are
      necessary in this area in order to more accurately define indications and dosage
      and method of reimbursement of blood in patient with severe trauma.

PMID- 20681211
TI  - [Carpal tunnel syndrome--surgical and anesthesiology considerations].
AB  - Carpal tunnel syndrome presents the most common peripheral nerve entrapment, and
      section of carpal transverse ligament is the most common procedure in peripheral
      nerve surgery. Favourable outcomes depend on several factors including correct
      diagnosis, careful patient selection, precise operative technique and appropriate
      postoperative care. The goal of this paper is to establish the most common causes
      of failed surgery analysing primary and secondary outcomes, and to give the
      possibility for better results in the future. Analysis was based on 250 operated
      patients. Primary outcome and secondary outcome 3 months after surgery was
      estimated. Total rate of complications was 8% with persistent complaints in 7
      (35%) patients and recurrent symptoms in 13 (65%) patients.

PMID- 20681212
TI  - [Topographic localisation of insertion of the anterior cruciate ligament].
AB  - INTRODUCTION: Determining the center of tibial insertion of the anterior cruciate
      ligament is important during reconstruction ligament. AIM: Determining the center
      of insertion of the anterior cruciate ligament on the anterior intercondylar area
      relate to anterior and medial edge of the upper end of tibia. MATERIAL AND
      METHODS: The messurement has been done on 102 tibia. We measured distance from
      the center of ACL to anterior and medial edge of the uper part of tibia, and the
      lenght and the width of the tibial insetion. Also, we showed the procentual ratio
      these distances with medio-lateral and anteroposterior diametar of upper tibial
      part. RESULTS: The distance between the centre of attachment and medial edge is
      at 39% from entire latero-medial diametar, while the distance from anterior edge
      is at 31% from entire anterio-posterior diametar. The possitive correlation
      between the distance of centar of the anterior cruciate ligament from anterior
      and inner edge (r = 0.366, p) was found. CONCLUSION: The center of the attachment
      of the ACL at anterior intercondylarl area is at 1/3 of antero-posterial diametar
      behind the anterior edge of the upper part of tibia and 2/5 of latero-medial
      diametar inside from the medial edge.

PMID- 20681213
TI  - [The position of anterior cuciate ligament in frontal and sagittal plane].
AB  - INTRODUCTION: Position of the anterior cruciate ligament (ACL) represents one of
      the anatomical factors which can lead to the rupture of the ligament. AIM: The
      aim of this study was to overview and compare gender and age differences of the
      position of the ACL and its relation with the medial aspect of the lateral
      femoral condyle. METHOD: The measurements were performed on the fifty cadaver
      knees (32 male and 18 female) aged between 15 - 53 years with intact ACL. We were
      measuring the angle of the ACL in sagittal and frontal plane and the angle of the
      medial aspect of the lateral condyle in frontal and horizontal plane. RESULTS:
      Measurements of the ACL in sagittal plane and measurements of the angle of the
      medial aspect of the lateral femoral condyle in horizontal plane showed
      statistically significant variations with the age (p < 0.05 and p < 0.01,
      respectively). The angle of the medial aspect of the lateral femoral condyle in
      frontal plane was statistically significant higher than the same measured angle
      in the horizontal plane ( p < 0.01). CONCLUSION: ACL fomis narrower angle with
      medial aspect of the lateral femoral condyle in extension of lower leg than in
      flexion as a result of smaller angle of the medial aspect of the lateral femoral
      condyle in frontal compared to horizontal plane.

PMID- 20681214
TI  - [Open fracture of the shin as an occupational injury and work capacity evaluation
      -case report].
AB  - Injuries at work (occupational injuries) represent a big social and economic
      problem. This case report presents the patient who suffered occupational injury-
      open fracture of the left shin. He has been hospitalized for several times at
      Orthopedic-Surgical Hospital "Banjica" and underwent several surgical procedures,
      physical therapy and Hyperbaric Oxygen Therapy. After this treatment, he was
      hospitalized at Institute of Occupational Health for disability evaluation and
      work capacity evaluation.

PMID- 20681215
TI  - [Injuries of the cervical spine in motorcycling and bicycling traffic accidents].
AB  - Due to the vehicle characteristics neck injuries are common in motorcycle and
      moped users involved in traffic accidents. We are reporting on neck injuries
      amongst 502 fatalities of drivers and passengers of motorcycles and mopeds, and
      cyclists. Cervical spine injuries were found in 124 cases (24.7%). Cervical spine
      injury was statistically significantly more frequently in passengers (61.9%)
      compared to the drivers (20.7%) of motorcycle and moped (chi2 = 13.384; p <
      0.01), the lesions are usually localized in the upper cervical spine (52.4%), the
      most frequently at atlantoocciptal region (F = 25.835; p); these injuries were
      most frequently caused by frontal (31.45%) or rear (50.81%) axial collisions.
      Almost all cases of cervical spine injuries were present without apparent
      external injuries; they were associated with lesions of neck muscles, blood
      vessels and/or neck organs, and in 79 cases (63.7%) there was a lesion of the
      cervical spinal cord. The research results indicate a large incidence of neck
      injuries in traffic accidents especially in motorcycle, moped and bicycle axial
      collision with the possible absence of external injuries, which may represent a
      clinical and forensic problem.

PMID- 20681216
TI  - Human tissue samples for research. A focus group study in adults and teenagers in
      Flanders.
AB  - A focus group study in adults and teenagers in Flanders: Attitudes towards
      research on human stored tissue samples may be dependent on the cultural context.
      To-day, no data exist on the attitudes and values of the Flemish population
      towards such research. To query these attitudes, we conducted ten focus groups,
      composed of adults and of minors on the verge of legal competence. Amongst the
      focus group participants, we found a trust in the advancement of science, and a
      willingness to contribute tissue to research. The importance attributed to
      informed consent depended on the type of tissue donated and the effort needed to
      contribute. Participants did not see high risk associated with research on stored
      tissue, but thought there was a need for confidentiality protections. The coding
      of samples was deemed an appropriate protection. With regard to the return of
      research results, people expected to receive information that could be relevant
      to them, but the meaning of what is relevant was different between individuals.

PMID- 20681217
TI  - Preconception care.
AB  - A good pregnancy outcome is partly determined by a women's preconceptional health
      and healthy lifestyle. The access to prenatal care is good nowadays but the
      incidence of congenital malformations, preterm births, low birth weight and
      maternal mortality has not significantly declined over the years. Although most
      women of reproductive age have a gynecological examination every two years in
      Belgium, they are not often counseled before starting a pregnancy. The American
      College of Obstetricians and Gynecologists (ACOG) states that optimizing a
      woman's health before and between pregnancies must be an ongoing process. The
      most vulnerable period for fetal defects is between 4 and 10 weeks of gestation,
      the period of embryogenesis, meaning that counseling for a healthy life style and
      reducing high-risk conditions should start preferably before conception.

PMID- 20681218
TI  - Balanced translocation in mother leading to interchange trisomy 21?
AB  - We report an unusual balanced translocation involving chromosomes 4 and 21 in a
      lady who had Down syndrome in her previous child. The most plausible explanation
      for this event is the 3:1 segregation of chromosomes at meiosis in her gametes
      leading to interchange trisomy 21.

PMID- 20681219
TI  - A unique case of a patient with partial trisomy 22 and lipodystrophy: is it a new
      syndrome due to an IGF-IR mutation?
AB  - A newborn male presented with intestinal malrotation, facial anomalies,
      hypertrichosis, hypertrophic, hyperpigmented nipples and enlarged genitals with a
      hyperpigmented scrotum. In addition, the patient displayed a marked lipodystrophy
      of trunk and limbs. His karyotype demonstrated a small supernumerary NOR-positive
      marker chromosome that was subsequently identified as del(22)(q12->qter). This
      extra structurally abnormal chromosome probably derives from a maternal balanced
      translocation, which was found by karyotype analysis of the mother. The patient's
      growth hormone (GH) serum levels were elevated, whereas serum insulin-like growth
      factor 1 (IGF-I) was almost undetectable. Molecular genetic analysis of the IGF-I
      and type 1 IGF receptor (IGF-IR) genes revealed a heterozygous mutation within
      exon 21 of the IGF-IR (Pro1257Ser). Findings in our patient correlate to a large
      extent with partial trisomy 22. Phenotypic variation from classical partial
      trisomy 22 syndrome may lie within the variability of this syndrome, originate
      from disturbances within the GH-IGF/IGF-IR axis or, alternatively, reflect the
      pathogenesis of a new syndrome due to the synergistical impact of the combination
      of the genetic aberrations. Additional studies are necessary to confirm or refute
      this hypothesis.

PMID- 20681220
TI  - Autism with del15p.11.1: case report with a new cytogenetic finding.
AB  - Autism with dell5Sp.11.1: case report with a new cytogenetic finding: Autism is a
      neurodevelopmental disorder and believed to be mainly genetic in origin, and
      environmental factors may modulate phenotypic expression. Less than four percent
      of cases of autism are associated with chromosomal abnormalities. Cytogenetic
      abnormalities found at the 15q11-q13 locus are reported most frequently in
      patients with autism. We performed GTG-banding and FISH studies to the present
      case and his parents and found a maternally inherited deletion on chromosome 15p
      in this case. With an understanding of the many genetic causes of autism,
      prenatal screening and counseling may one day become available for affected
      families as more autism-causing conditions become diagnosable.

PMID- 20681221
TI  - Two cases with partial trisomy 9: cytogenetic and clinical findings.
AB  - Partial trisomy syndrome of chromosome 9 is one of the frequent autosomal
      trisomies with a well defined phenotype. Here we report two cases with different
      karyotypes and we aim to compare the phenotypic findings. The first case was an
      8.5 months old boy with developmental delay. He had mental and motor retardation,
      microcephaly, bilateral undescended testes and multiple minor malformations. The
      karyotype was 46,XY,-7,der(7)t(7;9)(q36;p12) pat. The second case was a 5 year
      old boy with mental and motor retardation. He had atypical facial appearance with
      bilateral undescended testes. The karyotype was reported as 47,XY,+del(9)(q22.1
      qter)dn[46]/ 46,XY[4]. Partial trisomy 9 syndrome has a wide range of clinical
      findings depending on the size of the trisomic chromosome segment. Newly
      diagnosed cases and their chromosome findings will add to the understanding of
      the syndrome.

PMID- 20681222
TI  - Adipsic hypernatremia and bilateral renal stones in a child with ectrodactyly
      ectodermal dysplasia-cleft lip-palate (EEC) syndrome.
AB  - EEC syndrome an autosomal dominant disorder with variable expression and cardinal
      signs of ectrodactyly, ectodermal dysplasia, and orofacial clefts. In this
      report, we describe a patient with EEC syndrome, adipsic hypernatremia without
      brain anomalies, and bilateral renal stones, two manifestations that were not
      reported before.

PMID- 20681223
TI  - Bilateral split feet: a new finding in Cornelia de Lange syndrome.
AB  - We report on a male infant with Cornelia de Lange syndrome and bilateral split
      feet. Bilateral split feet do not appear to have ever been a reported feature in
      any of the published cases of Cornelia de Lange syndrome.

PMID- 20681224
TI  - A Turkish patient of typical Loeys-Dietz syndrome with a TGFBR2 mutation.
AB  - We describe a 2-year-old male patient with skeletal, neurological,
      cardiovascular, and connective tissue anomalies. Skeletal anomalies included
      pectus excavatum, hammer toes and hallux valgus and camptodactyly. The
      characteristic craniofacial findings of hypertelorism, down slanting palpebral
      fissures, strabismus, ptosis of eyelids, bifid uvula, high-arched palate and
      retrognathia were present. The proband has been operated on twice for bilateral
      inguinal hernia and several times for his foot deformities. Psychomotor
      development was retarded. At present, echocardiographic findings show aortic root
      dilation. The patient has important characteristics of Loeys-Dietz syndrome
      (LDS). Direct sequencing analysis of the transforming growth factor beta receptor
      I and II (TGFBR1 and 2) genes was performed and was demonstrated heterozygous
      missense mutation of the TGFBR2 gene in the patient, which confirms the diagnosis
      of LDS. This is the first Turkish patient with typical clinical signs of LDS.
      This report also illustrates that LDS and Shprintzen-Goldberg syndrome (SGS) have
      some common clinical characteristics.

PMID- 20681225
TI  - Unusual facial cleft in Fryns syndrome: defect of stomodeum?
AB  - Unusual facial cleft in Fryns syndrome: defect of stomodeum?: We report on a
      fetus with Fryns syndrome. The facial cleft was unusual. There was bilateral
      cleft lip with cleft palate. The intermaxillary segment was connected through the
      base of a mound in the midline to the lower lip. We believe this is an atypical
      facial cleft in Fryns syndrome and likely represents a defective stomodeum.

PMID- 20681226
TI  - A case with balanced reciprocal translocation t(5;11)(q32;q24.2) and situs
      inversus viscerum.
AB  - Situs inversus viscerum is a condition in which the organs of the chest and
      abdomen are arranged in a perfect mirror image reversal of the normal
      positioning. The condition is in about 1 in 8,500 people. Although the mechanism
      that causes the heart loop to go left is not fully understood, it is thought that
      many factors are involved. Here we report a case with balanced reciprocal
      translocation and situs inversus viscerum. The case was a 35 year old single
      person. In the imaging studies, his heart was on the right (dextrocardia), his
      liver was on the left, and his spleen was on the right. Cytogenetic study showed
      that the man carried a balanced reciprocal translocation: 46,XY,
      t(5;11)(q32;q24.2). He had no dysmorphism. He had chronic gastritis and chronic
      esophageal acid reflux.

PMID- 20681227
TI  - Effect of mobile phone station on micronucleus frequency and chromosomal
      aberrations in human blood cells.
AB  - The use of mobile telephones has rapidly increased worldwide as well as the
      number of mobile phone base stations that lead to rise low level radiofrequency
      emissions which may in turn have possible harm for human health. The national
      radiation protection board has published the known effects of radio waves
      exposure on humans living close to mobile phone base stations. However, several
      studies have claimed that the base station has detrimental effects on different
      tissues. In this study, we aimed to evaluate the effects of mobile phone base
      stations on the micronucleus (MN) frequency and chromosomal aberrations on blood
      in people who were living around mobile phone base stations and healthy controls.
      Frequency of MN and chromosomal aberrations in study and control groups was 8.96
      +/- 3.51 and 6.97 +/- 1.52 (p: 0.16); 0.36 +/- 0.31 and 0.75 +/- 0.61 (p: 0.07),
      respectively. Our results show that there was not a significant difference of MN
      frequency and chromosomal aberrations between the two study groups. The results
      claim that cellular phones and their base stations do not produce important
      carcinogenic changes.

PMID- 20681228
TI  - Chondrodysplasia punctata associated with tetralogy of Fallot in a newborn
      infant.

PMID- 20681229
TI  - Molecular basis of mental retardation in a sample from Bulgaria.

PMID- 20681230
TI  - Deletion 2q37.3->qter and duplication 15q24.3->qter characterized by array CGH in
      a girl with epilepsy and dysmorphic features.

PMID- 20681231
TI  - Fatigue and stimulant use in military fighter aircrew during combat operations.
AB  - INTRODUCTION: Fatigue in military aviation is a significant safety and
      operational problem resulting in diminished alertness and performance. Research
      demonstrates that stimulant medications maintain alertness and performance in
      sleep-deprived aircrew. However, these studies control many of the variables
      present during combat operations. Few studies have evaluated fatigue or the
      factors and effects associated with stimulant use in fighter aircrew during
      combat operations. METHODS: The study consisted of three questionnaires
      administered to 29 deployed F-1 5E aircrew participants. An initial questionnaire
      compiled demographic and sleep behavior data. Pre- and postflight questionnaires
      for each sortie collected substance use, fatigue, and physical symptoms data.
      Regression analysis identified variables associated with in-flight stimulant use.
      RESULTS: Surveys were completed for 111 sorties averaging 7.6 h in duration.
      Stimulants were used on 35% of sorties an average of 2.8 h after takeoff.
      Stimulant use was associated with a decrease in in-flight and postflight fatigue
      without significant differences in postflight symptoms. Sorties airborne during
      the circadian trough, longer sortie durations, and preflight hypnotic use
      displayed statistically significant associations with in-flight stimulant use.
      CONCLUSIONS: In-flight stimulants decrease fatigue during combat operations
      without significant postflight symptoms. During combat, stimulants were used
      earlier, at lower doses, and on shorter sorties than previously thought. The
      factors associated with stimulant use are potentially modifiable by improving
      training and aircrew scheduling practices. Furthermore, current policies
      authorizing stimulant use, based primarily on sortie duration, should also
      consider hypnotic use, inconsistent aircrew scheduling, and circadian disruption.

PMID- 20681232
TI  - Slalom walking with prism disorientation: impact on verbal and spatial tasks.
AB  - BACKGROUND: Slalom walking wearing distorting prisms has been used to study
      multitasking during adaptation to spatial disorientation. We address the
      hypothesis that slalom-prism walking could interfere specifically with concurrent
      spatial tasks. METHODS: Subjects (16 men, 16 women) sat for 30 s then slalom
      walked through 5 aligned batons. This exercise was performed with normal vision
      and with prisms deviating gaze laterally by 15.50 Both conditions were done
      without any tasks, with a verbal task (matching the sex of male and female names
      uttered by male and female voices), and a spatial task (matching laterality of
      the words 'right' and 'left' delivered to the right or left ear). Conditions were
      balanced with instructions to perform rapidly and accurately. RESULTS: Time to
      walk the slalom was extended by the prisms from 16 s to 33 s, but unaffected by
      tasks. Slalom increased error rates on the spatial task by 8% above baseline, but
      verbal task errors remained unchanged. Prisms did not affect task errors. The
      rates of processing cognitive task items were slowed by approximately 0.5 s by
      slalom and by 1 s slalom walking with prisms. Prisms increased task reaction
      times by 340 ms during slalom. Contact with the poles occurred when multitasking,
      with men making three times more contacts than women. CONCLUSIONS: Slowing of all
      performance parameters is consistent with a 'bottleneck' caused by task
      multiplexing. Competition for spatial processing resources and confusion because
      of similar features may cause interference between the lateralized spatial task
      and slalom.

PMID- 20681233
TI  - Time of day effects on neurobehavioral performance during chronic sleep
      restriction.
AB  - INTRODUCTION: Chronic nocturnal sleep restriction results in accumulation of
      neurobehavioral impairment across days. The purpose of this study was to
      determine whether time of day modulates the effects of sleep restriction on
      objective daytime performance deficits and subjective sleepiness across days of
      chronic sleep restriction. METHODS: There were N = 90 healthy adults (21-49 yr;
      38 women) who participated in a 14-d laboratory protocol involving randomization
      to 1 of 18 schedules of restricted nocturnal sleep with and without a diurnal nap
      for 10 consecutive days. The total time available for daily sleep ranged from 4.2
      h to 8.2 h across conditions. Performance lapses on the psychomotor vigilance
      test (PVT) and subjective sleepiness were measured each day every 2 h during
      scheduled wakefulness. Nonlinear mixed-effects regression was used to test the
      hypothesis that there would be an interaction between time of day and the
      accumulation (slope across days) of neurobehavioral sleepiness. RESULTS: In
      agreement with earlier studies, less sleep time resulted in faster accumulation
      of deficits across days. Time of day significantly affected this relationship for
      both PVT lapses and subjective sleepiness. The build-up rate of cumulative
      neurobehavioral deficits across days was largest at 0800 and became progressively
      smaller across the hours of the day, especially between 1600 and 2000. Following
      8 d of sleep restricted to 4 h/d, subjects averaged 8.3 more PVT performance
      lapses at 0800 than at 1800. DISCUSSION: This study provides evidence that the
      circadian system has a substantial modulatory effect on cumulative impairment
      from chronic sleep restriction and that it facilitates a period of relatively
      protected alertness in the late afternoon/early evening hours when nocturnal
      sleep is chronically restricted.

PMID- 20681234
TI  - Neuromuscular function following prolonged load carriage on level and downhill
      gradients.
AB  - INTRODUCTION: Decrements in muscle function may reduce physical and skilled
      performance and have been shown to be greater following walking unloaded on
      negative gradients. We examined the effects of prolonged walking with load
      carriage at level and negative gradients on muscle function. METHODS: There were
      10 male participants who completed two bouts of load carriage carrying a 25-kg
      backpack for 2 h at 6.5 km x h(-1) during level walking (LW) and downhill (-8%
      gradient) walking (DW). Force produced during voluntary and electrically
      stimulated contractions was measured before, 0, 24, 48, and 72 h post-exercise.
      RESULTS: Isometric knee extension force decreased immediately after LW (15 +/-
      11%) and DW (16 +/- 17%) and recovered to baseline at 72 h. Voluntary activation
      decreased immediately after LW (95 +/- 5 to 91 +/- 10%) and DW (97 +/- 4 to 94 +/
      12%) and returned to baseline at 24 h. Electrically stimulated 20:50 Hz tetani
      decreased after LW and DW, with complete recovery by 24 h after DW only. LW and
      DW caused decreases immediately after exercise in isokinetic peak torque of knee
      extensors and flexors at 60 degrees x s(-1) and 180 degrees x s(-1), trunk
      extensors and flexors at 15 degrees x s(-1), and shoulder flexors at 60 degrees x
      s(-1), with complete recovery at different time points, but all by 72 h.
      CONCLUSIONS: Level and downhill treadmill walking with load carriage resulted in
      similar changes in muscle function of the lower and upper body muscles
      immediately after exercise and during recovery. The decrements in muscle function
      may increase the risk of musculoskeletal injury and is likely to impair
      performance during physical and skilled tasks following load carriage.

PMID- 20681235
TI  - Chinese herbal medicine and cognitive and emotional functions during 60-day head
      down bed rest.
AB  - INTRODUCTION: This study aimed to test the efficacy of an oral-intake Chinese
      herbal medicine in enhancing the cognitive and emotional functions of individuals
      in a simulated microgravity condition. The herbal medicine consisted of
      ingredients that may enhance cognitive and emotional functions in an extreme
      environment. METHODS: There were 14 healthy male subjects who were randomly
      assigned to a Chinese medicine (CMG) or a control (CG) group and underwent a 60-d
      6 degree head-down bed-rest protocol. Testing was conducted before (Day -3),
      throughout (Days 3, 7, 20, 40, 57), and after (Days +3, +10) the bedrest
      protocol. The Arrow Test, Balloon Analog Risk Task (BART), Dual Task, and Affect
      Grid were administered on all testing days. RESULTS: The CMG demonstrated
      consistently higher scores on the BART (Days 20 to 40; Mean: CMG, 43.0 to 46.2
      and CG, 30.2 to 25.5) and lower levels of arousal on the Affect Grid (Days 7 to
      40; Mean: CMG, 6.9 to 6.7 and CG, 8.1 to 8.0) than did the CG. The CMG showed
      significantly higher performance on the Arrow Test (incompatible condition) at
      the beginning of the bed-rest period (Day 3 to 7; Mean: 799.5 ms and 763.1 ms,
      respectively) which was not observed in the CG. DISCUSSIONS: Results suggest that
      the Chinese herbal medicine may calm subjects' emotions by lowering the arousal
      level. At the same time, it may have produced positive effects in enhancing
      advantageous risk-taking and to a lesser extent self-regulatory behaviors (in the
      early phase).

PMID- 20681236
TI  - Biomechanical gender differences of the ankle joint during simulated half-squat
      parachute landing.
AB  - INTRODUCTION: A search of the literature did not reveal known gender differences
      in biomechanics during parachute landing. METHODS: Eight male and eight female
      healthy adults participated in this experiment. Each individual jumped from
      platforms with three different heights (low: 0.32 m; medium: 0.52 m; and high:
      0.72 m) and landed on flat ground in a standard half-squat parachute landing
      technique. The ground reaction force (GRF) normalized to bodyweight (BW), ankle
      joint kinematics, and the surface electromyogram (EMG) signals of the tibialis
      anterior (TA) and lateral gastrocnemius (LG) were measured. Two-way ANOVA was
      used to analyze the effects of the dropping height and gender factors. RESULTS:
      The anterior-posterior GRF (men 1.01 BW; women 0.79 BW), rate of loading (men 260
      BW x s(-1); women 127 BW x s(-1)), and absolute EMG amplitude of TA (pre-landing:
      men 219 microv; women 129 microv; post-landing: men 573 microv; women 288 microv)
      in the men's group were significantly higher than in the women's group, whereas
      peak angular velocity of dorsiflexion in the women's group (1627 degrees x s(-1))
      was significantly higher than in the men's (1188 degrees x s(-1)). DISCUSSION:
      Women are prone to transform the kinetic energy to the ankle motion, whereas men
      are more likely to transform it to friction. The co-contraction of the ankle
      flexor and extensor differs between genders. These factors may be associated with
      the higher incidence of parachute injuries among women reported by some authors.

PMID- 20681237
TI  - Application of a cardiovascular disease risk prediction model among commercial
      pilots.
AB  - INTRODUCTION: It has been suggested that integrated cardiovascular risk
      management guidelines and absolute cardiovascular risk prediction scores should
      be used routinely in aeromedical risk assessment. In this study a cardiovascular
      disease (CVD) risk prediction model has been applied to UK commercial pilots as
      an occupational group. METHOD: This retrospective cross-sectional study measured
      the variables age, sex, body mass index (BMI), blood pressure, use of
      antihypertensive medication, current smoking, and diabetes status of commercial
      pilots. Individual 10-yr absolute CVD risk scores (also referred to as 10-yr
      global CVD risk) were calculated using a non-laboratory based Framingham Heart
      Study developed model. RESULTS: Of the 14,379 subjects eligible for the study,
      none had missing values for risk factors. None of the female pilots and 9.7% of
      all male pilots were found to be high risk. The mean 10-yr absolute CVD risk for
      the entire pilot population was 8.41% (median 5.6). High-risk pilots are
      concentrated around 60 yr of age, (mean 59, median 60 yr) with an age range of 40
      81 yr. A sub-analysis of high-risk pilots younger than 65 revealed 1137 pilots in
      this group. CONCLUSION: The application of a 10-yr absolute CVD risk prediction
      model identified a group of pilots, previously unidentified, who may require a
      more comprehensive risk assessment. Pilots are continuing to fly commercially
      beyond the age of 60, which results in substantial increase in the CVD risk
      burden of the pilot population as a whole.

PMID- 20681238
TI  - Prevalence of low back pain (LBP) in rotary wing aviation pilots.
AB  - INTRODUCTION: The high prevalence of low back pain (LBP) in helicopter pilots has
      been well documented, although the reason behind it remains unclear. To date,
      little research exists comparing the Royal Air Force (RAF) to civilian pilots.
      METHODS: A questionnaire inquiring into participant demographics, flying
      experience, and back pain was distributed to RAF pilots based at units around the
      United Kingdom and civilian pilots working for groups such as Air Ambulance and
      Her Majesty's Coastguards. RESULTS: RAF pilots were significantly younger than
      civilian pilots (mean age 38.9 +/- 8.8 yr and 47.1 +/- 9.2 yr, respectively) and
      had been flying for a mode length of 6-10 yr compared with +26 yr in civilian
      pilots. Of civilian pilots, 40% had previously served as a pilot in the military.
      Neither RAF (83%) nor civilian (81%) pilots were significantly more likely to
      suffer from LBP and the nature of the pain experienced was similar. There were
      33% of RAF and 55% of civilian pilots who used a back support. DISCUSSION: The
      high prevalence of back pain reported by civilian and RAF pilots may be due to
      several factors. To investigate this further would require responses from a
      greater number of civilian pilots, particularly those who do not have previous
      military experience. In the meantime, further use of lumbar support may go some
      of the way to alleviating the problem.

PMID- 20681239
TI  - My car is sinking: automobile submersion, lessons in vehicle escape.
AB  - INTRODUCTION: In North America approximately 400 individuals per year die in
      submersed vehicles, accounting for 5-11% of all drownings. About half of people
      surveyed would let the vehicle fill with water before attempting exit. METHODS:
      We used a crane and two passenger vehicles of the same make, model, and year-one
      with passenger compartment intact (I) and one with holes (H) in the floor (area
      approximately 2200 cm2)--to conduct occupied and unoccupied submersions. RESULTS:
      Three phases of submersion were identified: 1) FLOATING, vehicles floated for 15
      s (H) to 63 s (I) before the water reached the bottom of the side windows; 2)
      SINKING, the subsequent period until the vehicle is completely under water, but
      before it fills completely; and 3) SUBMERGED, the vehicle was full of water and
      several feet below the surface. Total time to submersion was 150 s for I but only
      37 s for H. Opening the door to exit Vehicle I decreased submersion time from 150
      to 30 s. Even the most difficult exit strategy attempted (three men and a child
      manikin through one window) was quickly performed from Vehicle I (only 51 s).
      During one exit attempt, initiated during the sinking phase, it was impossible to
      open the doors or windows until the vehicle was completely full of water.
      CONCLUSIONS: A vehicle is most easily exited during the initial Floating Phase.
      We suggest the following escape procedure: SEATBELT(s) unfastened; WINDOWS open;
      CHILDREN released from restraints and brought close to an adult; and OUT,
      children should exit first.

PMID- 20681240
TI  - Contact urticaria from an oxygen mask in a military pilot.
AB  - Contact urticaria is a transient, wheal-and-flare response at the site of contact
      with a substance. We report a case of a military fighter pilot, with a background
      history of seborrheic dermatitis and steroid-induced facial skin atrophy, who
      subsequently developed contact urticaria from an oxygen facemask. Skin protection
      products such as barrier creams were used to try and minimize the provocation of
      contact urticaria from the oxygen mask whenever he flew, but without success. He
      was eventually permanently restricted from flying fighter aircraft.

PMID- 20681241
TI  - Brugada syndrome and fitness to fly: risk stratification in two pilot applicants.
AB  - Brugada syndrome is a condition associated with a characteristic ECG and sudden
      arrhythmic death. Due to this risk of sudden death, patients with Brugada
      syndrome are generally not considered fit to fly. In recent years we have gained
      new insight into this condition and Brugada syndrome patients can now be
      classified into different risk categories. This then raises the question of
      whether a subset of patients with the Brugada syndrome exists in whom the risk of
      sudden death is sufficiently low and is compatible with fitness to fly. We
      discuss this question with two case reports of persons with Brugada syndrome who
      applied for an airman medical certificate and we propose an algorithm to aid
      decision making in this situation.

PMID- 20681242
TI  - Decision-making and the management of airline operational disruptions.

PMID- 20681243
TI  - You're the flight surgeon: colloidal cyst of the third ventricle.

PMID- 20681244
TI  - Classics in space medicine. Human tolerance to multi-stage rocket acceleration
      curves.

PMID- 20681245
TI  - This month in aerospace medicine history.

PMID- 20681246
TI  - High points in aerospace physiology: a USAF perspective, Part II.

PMID- 20681247
TI  - [Drug addiction research using intravenous self-administration procedure in
      mice].
AB  - A major clinical problem in treating drug abusers or addicts is the high rate of
      relapse to abuse even long after abstinence. In drug dependence research, drug
      self-administration displays excellent face validity, good construct validity,
      and appealing predictive validity with respect to drug consumption in humans.
      Because of the technical feasibility of intravenous drug self-administration, it
      is limited in mice relative to larger animals. Nevertheless, technical
      innovations made in the last 10 years have vastly improved the feasibility of
      long-term studies in mice. In addition, mice with targeted gene mutations, such
      as transgenic and knockout mice, provide a powerful tool for investigating
      candidate genes that may be involved in abuse of drugs in humans. Therefore, it
      is essential for researchers to extend the extinction-reinstatement procedure in
      mice. However, there are few reports that proven the relationship between genetic
      factor and relapsing behavior using drug self-administration procedure in mice.
      Based on recent documented information and our own experiences, in the present
      review, we described some procedural considerations for the successful
      establishment of drug self-administration procedure in mice, and then summarized
      some behavioral characteristics of genetic mouse models under the drug self
      administration, and reinstatement procedure.

PMID- 20681248
TI  - [Alcohol consumption and metabolic syndrome].
AB  - Drinking excessive amounts of alcohol regularly for years is toxic to almost
      every tissue of the body. On the other hand, epidemiological and clinical
      evidence shows that light-to-moderate drinking is associated with a reduced risk
      of coronary heart disease, total and ischemic stroke, and mortality. In the past
      two decades, metabolic syndrome, the combination of obesity, hypertension,
      dyslipidemia and hyperglycemia, all are also recognized as major cardiovascular
      risk factors, has given rise to much clinical and research attention, because of
      its high prevalence in the world. Therefore, it is of interest to evaluate the
      overall associations of alcohol consumption with the development of the metabolic
      syndrome. Recently, the protective, detrimental, or J-shaped associations have
      been reported between alcohol consumption and the metabolic syndrome. This
      controversy may be due to the complex mechanistic relation between alcohol
      consumption and each component of metabolic syndrome, and almost all studies have
      various limitations and problem points. Prospective studies are therefore needed
      to confirm the association between alcohol consumption and prevalence of
      metabolic syndrome, and to assess the influence of alcohol drinking patterns and
      other possible factors, such as smoking, physical activity, socio-economic
      status, education, occupation, diet, and exercise. This article reviews the
      relation of alcohol consumption and components of the metabolic syndrome, and
      discusses the epidemiological evidence for alcohol's putative vascular protective
      effects and plausible underlying biological mechanisms.

PMID- 20681249
TI  - [Pharmacological properties and dependence liabilities of synthetic
      cannabinoids].
AB  - Since 2000, types of abused drugs have increased in Japan and abused drugs are
      diversifying. Chemicals with structures similar to the drugs and stimulants
      restricted by law are sold as medicines that are not so restricted. Furthermore,
      drugs that have evaded attention of the law and abuse of these drugs are
      increasing rapidly. Serious health hazards are occurring from abuse of these
      chemicals as well as existing abused drugs: they are thus causing a major social
      problem. Synthetic cannabinoids, one of these illegal drugs, is called "spice"
      and its abuse is spreading all over the world. So far, Germany and Japan have
      analyzed the ingredients of the spice series. Synthetic cannabinoids that have
      actually been detected include CP-47497 and its variations with different numbers
      of carbon atoms in the side chain, i.e., CP-47497-(C8), JWH-018, etc. Cases of
      drug dependence and health hazards, such as mental diseases, caused by abuse of
      spice have been reported, revealing their danger. Numerous synthetic cannabinoid
      derivatives emerged during the development of medicines, and the methods for
      synthesizing them and the strength of their binding affinity with the cannabinoid
      receptor have also been clarified. Under current conditions, when particular
      synthetic cannabinoid derivatives are restricted, others soon replace them.
      Although the biochemical characteristics of synthetic cannabinoid derivatives,
      such as binding affinity with receptors, have been clarified, actions of
      synthetic cannabinoid derivatives that are taken are still unknown for most
      derivatives. Some cannabinoid derivatives exhibit tens of times the strength of
      delta 9-THC, an ingredient of hemp, so it is feared that taking them may cause
      unexpected serious health hazards.

PMID- 20681250
TI  - [Prognosis of drug dependent persons discharged from rehabilitation center in
      Japan and related factors: one year follow-up data].

PMID- 20681251
TI  - [Effect of ethanol on sphingosylphosphorylcholine (SPC)-induced vasoconstriction
      in rat artery].

PMID- 20681252
TI  - [Intraocular pressure reduction and bleb-related infections in glaucoma
      treatment].

PMID- 20681253
TI  - [Pathogenesis of macular edema associated with branch retinal vein occlusion and
      strategy for treatment].
AB  - We summarize the pathogenesis and the treatment strategy for macular edema in
      patients with branch retinal vein occlusion (BRVO), focusing on the role of the
      cytokines. Various cytokines are involved in the pathogenesis of macular edema
      associated with BRVO. When BRVO occurs, it leads to retinal ischemia that induces
      the production of cytokines such as vascular endothelial growth factor (VEGF) by
      retinal cells such as glial cells and vascular endothelial cells in the occluded
      region affected by anoxia. These cytokines interact with each other (cytokine
      network) and this results in impairment of the blood-retinal barrier and an
      increase of vascular permeability, considered important in the development of
      macular edema associated with BRVO. Treatment for this condition includes
      triamcinolone acetonide, anti-VEGF antibody, laser therapy and vitrectomy, all of
      which lead to the suppression of cytokine production. To manage macular edema
      associated with BRVO, it is important to control cytokine production with a
      combination of treatments.

PMID- 20681254
TI  - [Study on relationship between control of intraocular pressure and systemic risk
      factor for visual field progression in normal-tension glaucoma].
AB  - PURPOSE: To study the relationship between the reduction of intraocular pressure
      (IOP) and visual field (VF) damage in normal-tension glaucoma (NTG) patients with
      or without systemic risk factors. METHODS: Ninety-two eyes of 92 patients with
      NTG were enrolled in this study. All patients were followed up for more than 2
      years of taking topical antiglaucoma medications. Personal history regarding
      migraine, diabetes mellitus, hypertension, cerebrovascular disease,
      cardiovascular disease, Raynaud's phenomenon, arrhythmia, and family history of
      glaucoma were collected from the medical records. The survival data were analyzed
      using regression analysis based on the Cox proportional hazards model. The
      relationship between the presence of each systemic factor and the effect of
      reduction of VF progression were evaluated using the life table analysis.
      RESULTS: The progression of VF damage was significantly associated with IOP (p =
      0.020). The eyes with larger IOP reduction showed significantly less VF
      progression than eyes with smaller IOP reduction both in patients with and
      without systemic diseases (with systemic diseases p = 0.027, without systemic
      diseases p = 0.025) and a family history of glaucoma (p = 0.019). In patients
      with a family history of glaucoma, the rate of VF progression did not show
      statistically differences between the eyes with larger IOP reduction and those
      with smaller IOP reduction. CONCLUSIONS: IOP reduction is beneficial in reducing
      the risk of VF progression regardless of the presence of systemic risk factors in
      patients with NTG.

PMID- 20681255
TI  - [Risk factors for visual outcome after bleb-related infection].
AB  - PURPOSE: To investigate risk factors for visual impairment following bleb-related
      infection after trabeculectomy with mitomycin C. METHODS: We retrospectively
      reviewed 31 cases of bleb-related infection at Osaka Koseinenkin hospital from
      2004 to 2007. RESULTS: Twelve cases of blebitis and 19 cases of bleb-related
      endophthalmitis were studied. According to the stage of infection, each patient
      was continued to be treated following a previously decided treatment strategy.
      Fifteen patients underwent pars plana vitrctomy. Two patients with blebitis
      progressed to endopthalmitis. Visual acuity in seven eyes (22.6%) decreased by
      two or more lines following infection. Risk factors for visual impairments
      following bleb-related infections were recurrence of infection (p = 0.022),
      negative Seidel tests (p = 0.0056), aphakia (p = 0.045), avitreous (p = 0.00070),
      positive Streptococcus species (p = 0.029), and prolonged inflammation (p =
      0.014). CONCLUSIONS: Recurrence of infection, negative Seidel tests, aphakia and
      avitreous are risk factors for visual impairment following bleb-related infection
      after trabeculectomy.

PMID- 20681256
TI  - [Microbial contamination of nipradiol with and without benzalkonium chloride].
AB  - PURPOSE: To compare microbial contamination of nipradiol both with and without
      benzalkonium chloride (BAC). SUBJECTS AND METHODS: Twenty primary open angle
      glaucoma patients treated with nipradiol with BAC were studied. The nipradiol
      with BAC was switched to nipradiol without BAC. Four weeks after switching, the
      nipradiol without BAC was once again switched to nipradiol with BAC. The bottle
      caps, nozzles, filters, and solutions were cultured and examined for
      contamination. RESULTS: In nipradiol without BAC microorganisms were isolated
      from caps (30%), nozzles (50%), solutions (0%), and filters (15%), whereas in
      nipradiol with BAC they were isolated from caps (35%), nozzles (40%), and
      solutions (25%). The microorganisms in the nipradiol without BAC were coagulase
      negative Staphylococci (38.2%) and Propionibacterium acnes (29.4%), and in the
      nipradiol with BAC they were coagulase-negative Staphylococci (20.5%),
      Alcaligenes xylosoxidans (12.8%). CONCLUSIONS: In nipradiol without BAC, the
      bacteria were detected outside the filters, but not in the solution. The rate of
      microbial contamination of the nipradiol without BAC was similar to that of the
      nipradiol with BAC. Both the bacteria detected from the nipradiol with and those
      detected in the solution without BAC consisted only of bacterial flora of the cul
      de-sac and skin.

PMID- 20681257
TI  - [The effectiveness of intravitreal administration of bevacizumab for choroidal
      neovascularization in retinal angioid streaks].
AB  - PURPOSE: To investigate the effectiveness of intravitreal administration of
      bevacizumab (IVB) for choroidal neovascularization (CNV) in retinal angioid
      streaks (AS). SUBJECTS AND METHODS: Five eyes of four subjects with CNV in AS
      were observed for an average followup period of 12 months. The average greatest
      linear diameter (GLD) of the AS was 4315 microm before treatment. IVB (1.0 mg or
      1.25 mg) was performed a total of two times at eight week intervals, and
      additional bevacizumab was administered whenever exudative changes occurred.
      RESULTS: Visual acuity improved in one eye (20%), was maintained in two eyes
      (40%), and worsened in two eyes (40%). Recurrence of CNV was observed in two eyes
      (40%). Before treatment, the GLD was 2439, 2844, and 3654 microm in the three
      eyes in which visual acuity was maintained, and 5803 and 6837 microm in the two
      eyes with worsened visual acuity. Recurrence of CNV was observed in the two eyes
      with worsened visual acuity. CONCLUSION: Short-term CNV fibrosis and maintenance
      of visual acuity were achieved with IVB in cases in which the GLD was less than
      3500 microm.

PMID- 20681258
TI  - [A case of frosted branch angiitis associated with retinal vein occlusion as a
      complication of familial Mediterranean fever].
AB  - BACKGROUND: Familial Mediterranean fever (FMF) is characterized by recurrent
      episodes of fever and serositis caused by autosomal recessive inheritance MEFV
      gene mutations. It is reported that the onset of angiitis is high among patients
      with this disease, but no reports were found in the field of ophthalmology in
      Japan. In this paper, we report one case that developed from optic disc
      vasculitis to frosted branch angiitis associated with retinal vein occlusion.
      CASE: A 39 year old male. Fever, abdominal pain and chest pain were continued
      from childhood. In 2006, an idiopathic fever was reported with a renal disorder.
      Based on the results of laboratory examinations, he was diagnosed with FMF and
      started oral colchicines to stabilize the symptoms. In October 2007, he
      complained of blurry vision in his left eye that lasted for about one week prior
      to his visit and decided to visit our department for an examination. Visual
      acuity was right 1.5 and left 1.2. Although no abnormalities were found in the
      anterior chamber or optic media of either eye, the left eye papilla was reddish
      and swollen, and varicose enlargement of the retinal veins and a small retinal
      hemorrhage were found. Four days later, a white vascular infiltration spread to
      all branches of the retinal veins at the upper-half of the left eye papilla, the
      hemorrhage increased in the entire retina and the visual acuity decreased to 0.1.
      He was hospitalized and systemic administration of an antiviral agent, an
      antibacterial agent and a steroidal agent (prednisolone 60 mg/day) was started.
      Subsequently, the left eye ocular fundus findings slowly improved and he was
      cured 7 months later with a visual acuity of 1.0. CONCLUSION: Frosted branch
      angiitis may occur with systemic gene abnormalities as an underlying condition
      and it is important in the future to consider FMF as a causative disease.

PMID- 20681259
TI  - [A review 43: Congenital optic disc anomalies and retinal detachment].

PMID- 20681260
TI  - [Advances in induced pluripotent stem cell research for neurological diseases].
AB  - In 2006, Takahashi and Yamanaka reported a groundbreaking study showing mouse and
      human somatic cells that can be reprogrammed to the pluripotent state by
      expression of only a few transcription factors (Oct4, Sox2, Klf4, and c-Myc).
      This novel strategy can be used for transplantation therapies without immune
      rejection providing additional advantages regarding ethic issues of oocyte
      donation. For neurological diseases, disease-specific induced pluripotent stem
      (iPS) cells may serve as an invaluable model for clarifying pathogenesis and for
      screening new drug therapies. In particular, differentiated neurons derived from
      patient iPS cells could infinitely provide an alternative cellular-biochemical
      material for research instead of biopsy and autopsy. This review summarizes the
      current studies applying iPS cells in the field of neurology and discusses their
      potential and limitations for therapy against neurological diseases.

PMID- 20681261
TI  - [Ischemic stroke under anticoagulant therapy].
AB  - In order to determine predictive factors of stroke recurrence during
      anticoagulant therapy and to estimate prognosis, we retrospectively examined
      clinical data of 197 consecutive patients with acute ischemic stroke. The
      subjects were divided into two groups, within the therapeutic range group and
      below therapeutic range group, based on Japanese guidelines for the management of
      stroke 2004. Univariate analysis revealed that cardioembolic stroke patients were
      less frequent in the therapeutic range group (61% vs 77%; p = 0.03), while more
      lacunar stroke patients were experienced (17% vs 6%; p = 0.01). In patients with
      past history of cardioembolic stroke, significant favorable outcomes as of
      Barthel index (54 vs 33; p = 0.03) and modified Rankin Scale (3 vs 4; p = 0.04)
      were found within the therapeutic range group. There is a possibility that
      adequate anticoagulation prevents thrombogenesis or lead to early recanalization,
      especially in patients with past history of cardioembolic stroke.

PMID- 20681262
TI  - [A case of acute disseminated encephalomyelitis associated with Epstein-Barr
      virus reactivation during infliximab therapy].
AB  - A 31-year-old woman with Crohn's disease that had been refractory to drug
      therapies for 7 years had been treated with infliximab for a year. She was
      admitted to our hospital because of truncal ataxia and bulbar palsy, which
      presented following aseptic meningitis. Neurological examination revealed
      abducens paresis on the left, gaze-evoked nystagmus on upward and rightward gaze,
      right facial muscle weakness, bulbar palsy, weakness in the right upper
      extremity, limb ataxia predominantly on the left side, diminished sense in the
      lower extremities predominantly on the right, diffuse hyperreflexia in all
      extremities. Antibodies to Epstein-Barr virus (EBV) in serum demonstrated a
      previous infection pattern, and EBV-DNA was detected in peripheral blood and
      cerebrospinal fluid (CSF) by PCR. CSF analysis indicated pleocytosis, an
      elevation of IgG index and a marked increase in the level of myelin basic
      protein. FLAIR MRI images revealed multiple hyperintense lesions in the
      brainstem, subcortical white matter, and cervical spinal cord. Accordingly, we
      diagnosed her as having acute disseminated encephalomyelitis (ADEM), associated
      with reactivated EBV infection. Although gancyclovir, plasma exchange and
      intravenous high dose immunoglobulins were not effective, repetitive use of
      methylprednisolone pulse therapy alleviated her symptoms and the abnormal MRI
      lesions. It is suggested that the reactivated EBV infection caused by infliximab
      may have contributed to the development of ADEM in this case. Besides the
      demyelinating event directly induced by anti-TNF-alpha therapy, we should pay
      attention to the occurrence of reactivated EBV-triggered ADEM during anti-TNF
      alpha therapy.

PMID- 20681263
TI  - [A case of anti-Hu antibody- and anti-GluR epsilon2 antibody-positive
      paraneoplastic neurological syndrome presenting with limbic encephalitis and
      peripheral neuropathy].
AB  - We report a case of paraneoplastic neurological syndrome with anti-neuronal
      antibodies, namely anti-Hu and anti-GluR epsilon 2 antibodies in sera. A 72-year
      old male had a transient history of eye movement disorder and sensory neuropathy,
      which improved spontaneously. Two years later, he was admitted to another
      hospital because of gait disturbance, numbness of the hands and an attack of
      unconsciousness with generalized convulsion. He was admitted to our hospital with
      prolonged consciousness disturbance and muscular weakness of all extremities. On
      admission his consciousness deteriorated slightly without neck stiffness. His
      cranial nervous system was normal except for incomplete abduction and elevation
      of both eyes. The patient had severe distal dominant weakness and atrophy in the
      muscles of all four limbs. Muscle tonus was decreased and hyporeflexia was noted
      in the four extremities. Plantar response was extensor. Neither sensory
      disturbance nor ataxia was observed. Cranial MRI showed T2-weighted high
      intensity lesions in the bilateral mesial temporal lobes, including the
      hippocampi. A nerve conduction study revealed motor-dominant peripheral
      neuropathy with prolonged latency; the amplitudes of compound muscle action
      potentials were severely reduced in all four limbs and those of sensory nerve
      action potentials were moderately reduced in the right upper and lower
      extremities. We also found a left hilar lymphadenopathy showing accumulation of
      FDG on PET, suggesting a possibility of malignancy. Anti-Hu and anti-GluR epsilon
      2 antibodies were detected in sera but not in CSF. We diagnosed him with limbic
      encephalitis and peripheral neuropathy due to paraneoplastic neurological
      syndrome and treated him with two courses of intravenous immunoglobulin (IVIg)
      (400 mg/kg, 5 days). The consciousness disturbance, and prolonged distal latency
      revealed by motor nerve conduction studies improved slightly. Although the roles
      of anti-neuronal antibodies in paraneoplastic conditions remain unknown, we
      consider that IVIg may be worth using to treat cases with anti-Hu and anti-GluR
      epsilon 2 antibodies.

PMID- 20681264
TI  - [Three patients with transient global amnesia following an increased venous
      pressure: a study using 3.0 Tesla diffusion-weighted magnetic resonance imaging].
AB  - We present 3 patients with transient global amnesia (TGA). Patient 1 was a 67
      year-old man who had developed TGA 5 years ago. He showed sudden onset amnesia
      immediately after he quarreled with his wife loudly during driving. Three-Tesla
      (3T) diffusion-weighted magnetic resonance imaging (DWI) taken 18 hours after
      onset revealed a small hyperintense signal area in the right CA1 subfield of the
      hippocampus. Patient 2 was a 66-year-old woman who showed sudden onset amnesia
      immediately after she walked for about 20 minutes holding a heavy luggage with
      her arms. 3T DWI taken 64 hours after onset revealed a small hyperintense signal
      area in the left CA1 subfield of the hippocampus. Patient 3 was a 68-year-old
      woman who showed sudden onset amnesia immediately after she hurriedly cleaned up
      her house with a cleaner. 3T DWI taken 48 hours after onset revealed small
      hyperintense signal areas in the left CA1 subfield and the right subiculum proper
      of the hippocampus. She developed TGA recurrence 6 months after the first episode
      of TGA. All these 3 patients had no cardiovascular diseases. Their amnesia
      resolved within 5-6 hours. Magnetic resonance venography (MRV) revealed
      hypoplasia of the left transverse sinus in Patient 1 and Patient 3, and aplasia
      of the left transverse sinus in Patient 2. Ultrasound studies revealed a
      retrograde flow component of internal jugular vein during Valsalva maneuver in
      Patient 2. We speculate that an increased venous pressure might have precipitated
      cerebral venous ischemia in the hippocampus, which is most vulnerable to ischemic
      insults.

PMID- 20681265
TI  - [A case of Lissauer form of paretic neurosyphilis with drop attacks and
      dementia].
AB  - A 52-year-old man was admitted to our hospital due to drop attack accompanied
      with progressive right hand's clumsiness and recent memory impairment.
      Neurological examination revealed postural involuntary movement of the right
      hand, and impaired finger fine movements. He showed mild mental deterioration
      with lower MMSE score. Toreponema Pallidum Latex immuno Assay (TPLA) titers in
      serum and cerebrospinal fluid (CSF) were remarkably elevated. MRI revealed
      cerebral atrophy in the left hemisphere. The 99mTc-ECD SPECT analysis showed
      reduced cerebral blood flow in the left hemisphere. EEG showed slow background
      activity in the left hemisphere. Drop attacks and involuntary movement were
      diminished by the administration of the valproate. We diagnosed this case as
      Lissauer's general paresis and treated with intravenous benzylpenicillin
      potassium 24 million units per day for 2 weeks. After this treatment, the titer
      of TPLA in the serum and CSF decreased. The clinical symptoms and signs, the
      score of MMSE, findings of SPECT and EEG also improved. Although Lissauer's
      general paresis is a rare form of neurosyphilis, it is important to distinguish
      this disease in case of progressive dementia and focal neurological signs. Early
      diagnosis and treatment are the only way to prevent irreversible neurological
      damage in this disease.

PMID- 20681266
TI  - [A case of mononeuropathy multiplex associated with idiopathic thrombocytopenic
      purpura].
AB  - We report a case of mononeuropathy multiplex with idiopathic thrombocytopenic
      purpura (ITP). A 78-year-old man developed patches of purpura on his left
      forearm. His platelet count was 11,000/microl and platelet-associated IgG was
      elevated. He was diagnosed as having ITP. At the beginning of the following
      month, he noticed dysesthesia and weakness of his left finger and left lower
      limb, as well as dysesthesia of his bilateral lower thighs. Neurological
      examination revealed weakness in the area of the left ulnar nerve and of the left
      anterior tibial muscle. Dysesthesia presented in the area of the left ulnar nerve
      and bilateral superficial peroneal nerves. Nerve conduction studies revealed
      asymmetric axonal sensorimotor neuropathy (mononeuropathy multiplex). A
      cerebrospinal fluid specimen showed a normal cell count and normal protein level
      Serum anti-ganglioside antibody was negative. The platelet count gradually
      increased after the introduction of corticosteroid therapy. His neurological
      deficits and electrophysiological findings also improved. Immune-mediated
      neuropathy was suggested as the cause of his mononeuropathy multiplex with ITP.

PMID- 20681267
TI  - [A case of progressive supranuclear palsy with late-onset supplementary motor
      area seizure].
AB  - We report a 75-year-old, right-handed man, presenting with supplementary motor
      area (SMA) seizure. The patient had suffered from frequent attacks of transient
      inability to speak and move without loss of awareness. On admission, he presented
      with vertical gaze paresis, axial rigidity, paratonia of extremities and gait
      disturbance. The attacks were preceded by discomfort on the head, followed by
      inability to move the whole body and arrest of vocalization with tonic posture
      and exaggerated breathing. Consciousness and cognitive function were preserved
      throughout the attacks. Electroencephalography recorded intermittently slow theta
      waves in the bifrontal regions. Brain MRI showed atrophy of the midbrain
      tegmentum with lacunar state suggesting progressive supranuclear palsy. SPECT
      with 123I-iomazenil revealed decreased uptake in the medial frontal areas
      including SMA, bilaterally. The seizures resolved completely following treatment
      with carbamazepine. Based on clinical features and neuroimagings, we speculated
      that the negative motor area within SMA was responsible for his seizure.
      Physicians should keep in mind that SMA seizure comprising negative motor
      phenomenon can occur in the elderly.

PMID- 20681268
TI  - [Recurrent idiopathic hypertrophic pachymeningitis after surgery of chronic
      otitis media with cholesteatoma: a case report].
AB  - A 70-year-old woman visited our hospital because of a chronic headache four years
      ago. MRI demonstrated almost symmetrically thickened dura mater in the frontal
      and parietal regions. She was diagnosed with idiopathic hypertrophic
      pachymeningitis and received corticosteroid therapy. Corticosteroid therapy
      improved her clinical symptoms and thickening of the dura mater. She remained
      free of neurological symptoms after prednisolone was tapered to 5 mg/day.
      However, three years ago, she developed ear pain, otorrhea and hearing loss on
      the left side. She was diagnosed as having otitis media with cholesteatoma last
      year, and underwent mastoidectomy and tympanoplasty on the left side three months
      ago. After surgery, she recovered from the ear symptoms, but noticed a headache
      on the left side. Three months after the surgery, MRI demonstrated the recurrence
      of hypertrophic pachymeningitis in the frontal and parietal regions, particularly
      on the left side. Corticosteroid therapy again improved the headache and
      thickening of the dura mater. The finding that the patient recovered after
      corticosteroid therapy alone suggests that non-infectious inflammation played a
      major role in the pathogenesis. Chronic inflammation associated with otitis media
      with cholesteatoma or surgical invasiveness might induce the recurrence of
      idiopathic hypertrophic pachymeningitis.

PMID- 20681269
TI  - [Creating a 'Germanic' public health: national-socialism, human genetics, and
      eugenics in the Netherlands].
AB  - The consequences of the uses of concepts of heredity in society and health care
      are not simply determined. This is demonstrated by a study of Dutch National
      Socialist doctors and biologists in the Second World War. During the German
      occupation of the Netherlands SS-biologist W.F.H. Stroer (1907-1979) and SS
      doctor J.A. van der Hoeven (1912-1998) attempted to create a eugenic research and
      health care institute in the Netherlands. Heredity was accorded a key role in
      National Socialist plans for reorganization of Dutch health care. The ideas of
      the SS-eugenicists were closely related to those of leading geneticists and
      eugenicists in the Netherlands. Eugenic ideas were spread among all political
      ideologies. As late as November 1942 cooperation between the SS and non-Nazi
      geneticists was still discussed. The hardening of the political climate during
      the war created more explicit dividing lines between them. The SS-researchers did
      not believe in the existence of well-defined and separated races. They rejected a
      purely genetic determinism and advocated measures of social hygiene next to a
      positive and negative eugenics in the creation of a more healthy Germanic people
      and a purer race. Racial and genetic concepts were not exclusively translated
      into eugenic policies directed at human reproduction.

PMID- 20681270
TI  - [Integrative Chinese and Western medicine research on hypertensive disease].

PMID- 20681271
TI  - [Correlation study on serum adiponectin abnormity with adiponectin gene
      polymorphisms in hypertensive patients of phlegm-dampness constitution].
AB  - OBJECTIVE: To explore the difference of serum adiponectin (APN) level in
      hypertensive patients of phlegm-dampness constitution (PDC) and in those of non
      PDC, as well as its association with APN gene polymorphisms. METHODS: Serum APN
      levels in 250 hypertensive patients (137 of PDC and 113 of non-PDC) were
      determined, and a correlation study was performed on 8 selected single nucleotide
      polymorphism (SNP) of APN gene. RESULTS: Significant differences of serum APN
      levels were observed between PDC and non-PDC patients (5.07 +/- 0.35 microg/mL vs
      6.41 +/- 0.39 microg/mL, P = 0.045). No significant difference in polymorphism
      distribution of the 8 SNP sites of APN genes was found between patients of
      different constitutions (P > 0.05). Serum APN level was significantly lower in
      PDC patients than in non-PDC patients in sites of APN gene rs1063537 (3224C/T)
      polymorphism TT genotype (2.580 +/- 1.029 microg/mL vs 6.011 +/- 0.945 microg/mL,
      P = 0.017) and CT genotype (5.113 +/- 0.968 microg/mL vs 7.812 +/- 0.161
      microg/mL, P = 0.021), while that of CC genotype was insignificant between the
      two constitutions (5.426 +/- 0.591 microg/mL vs 6.130 +/- 0.668 microg/mL).
      CONCLUSION: Serum APN level was significantly lower in hypertensive patients of
      PDC than in those of non-PDC. Moreover, the APN gene SNP3224 T allele carrier
      might be a hereditary feature of APN abnormity.

PMID- 20681272
TI  - [Relationship between gene polymorphism and haplotype of SLC6A2 promoter and
      blood-stasis pattern in patients with essential hypertension].
AB  - OBJECTIVE: To explore the relationship between the genetic variants of the
      norepinephrine transporter gene solute carrier family 6 member 2 (SLC6A2) and
      blood stasis pattern (BSP) in patients with essential hypertension (EH). METHODS:
      DNA was extracted from the peripheral blood of 830 EH patients (532 were typed as
      BSP and 298 as non-BSS) and 512 persons with normal blood pressure (for control),
      to detect the polymorphisms of SLC6A2 promoter-3 and 2 by PCR-RFLP, and estimate
      the haplotype frequency adopting SHEsis program. RESULTS: Chi2 partition showed
      that frequency of promoter-2-GG genotype in EH patients of BSP was lower than
      that in the EH patients of non-BSP and the normal control (P = 0.001); while that
      of promoter-3-GG/GA in the EH patients with severe BSP was the highest (P <
      0.001). Logistic regression analysis showed that after the miscellaneous factors
      being rectified, with the reference category of EH-non-BSP, the relative odds
      ratio (OR) of promoter-2-GC/CC genotype for EH-BSP was 1.535 (95% CI: 1.094
      2.155, P = 0.013); that of promoter-3-AG/GG genotype for EH with severe BSP was
      1.925 (95% CI: 1.199-3.091, P = 0.007); while OR of G-C haplotype (promoter-3
      promoter-2) for EH-BSP was 2.127 (95% CI: 1.202-3.765, P = 0.010), showing the
      strongest intensity. CONCLUSION: SLC6A2 promoter-3-GA/GG genotype may be a
      susceptibility gene for patients of EH with severe BSP; promoter-2-GC/CC and G-C
      haplotype might be the susceptible factors to EH-BSP.

PMID- 20681273
TI  - [Effects of combined application of xuezhikang capsule with hypotensive drugs on
      arterial compliance and smoothness of the dynamic blood pressure].
AB  - OBJECTIVE: To investigate the effects of combined application of Xuezhikang
      Capsule (XZK) and hypotensive drugs on the dynamic blood pressure (DBP), pulse
      pressure index (PPI), pulse wave velocity (PWV) and smoothness index (SI), and to
      study the relationship between SI and related factors (age, BP, dynamic PPI, and
      vascular elasticity). METHODS: One hundred and ten patients with essential
      hypertension were randomly assigned to 2 groups: 54 in the control group and 56
      in the treated group. Both were treated with hypertensive drugs, but with oral
      medication of XZK given additionally to the treated group at the dose of 60 mg,
      twice a day. PWV and DBP were measured before treatment and at the terminal of a
      6-month treatment. Meantime, the 24-h average systolic and diastolic pressures
      were recorded to calculate the 24-h dynamic pulse pressure (24 hPP), PPI, SI of
      systolic and diastolic blood pressure (SISBP and SIDBP) for comparing the changes
      between groups and analyzing the SI related factors. RESULTS: All patients' blood
      pressure levels were well controlled; after a 6-month treatment, the PP and PPI
      in the treated group were 45 +/- 8 mm Hg and 0.35 +/- 0.08 respectively, which
      were significantly lower than those in the control group (51 +/- 10 mm Hg and
      0.38 +/- 0.05, P < 0.05); while SISBP and SIDBP in the treated group were higher
      than those in the control group (1.37 +/- 0.16 vs 1.26 +/- 0.20, P < 0.01; and
      1.28 +/- 0.14 vs 1.18 +/- 0.23, P < 0.05) respectively; and PWV in the former was
      significantly lower than that in the latter group (10.4 +/- 3.68 m/s vs 12.5 +/-
      4.27 m/s, P < 0.05). Multiple factor stepwise regression analysis showed that the
      SISBP was negatively correlated with age, PPI and PWV, while the SIDBP was
      negatively correlated with PPI (P < 0.01). CONCLUSION: The combined application
      of XZK and hypotensive drugs can decrease PP and PPI, improve the endothelial
      function and arterial elasticity, enhance the efficacy of treatment on SI. After
      treatment SI shows a significant negative correlation with PPI, PWV and age in
      patients.

PMID- 20681274
TI  - [Screening, identification and analysis of platelet differential functional
      proteins in patients with coronary heart disease of blood-stasis pattern].
AB  - OBJECTIVE: To seek the key platelet functional proteins (PFPs) for the occurrence
      of blood-stasis pattern (BP) in patients with coronary heart disease (CHD).
      METHODS: Peripheral blood platelet protein of 22 patients and 24 healthy person
      (for control) were extracted respectively in 4 batches for carrying 4 times of
      the test out. Differential PFPs in samples were screened out by two-dimensional
      fluorescence difference gel electrophoresis, and identified with matrix-assisted
      laser desorption/ionization-time of flight mass spectrometry; then the identified
      proteins were further authenticated by Western-blotting. RESULTS: Thirteen
      differential PFPs were screened out, and among them the 7 identified by
      spectrometry were: isoform 1 of integrin alpha- II b, isoform 2 of integrin alpha
      II b, actin-cytoplasmic 1, actin-cytoplasmic 2, cDNA FLJ52842, cDNA FLJ55253,
      and cDNA FLJ43573 fis. Among them isoform 2 of integrin alpha- II b (CD41) and
      actin-cytoplasmic 2 (Acting) were authenticated successfully. CONCLUSION: CD41
      and acting are the possible marker proteins, and the other PFPs might play
      crucial roles in the occurrence and development of BSS in CHD.

PMID- 20681275
TI  - [Evaluation on clinical effect of long-term shexiang baoxin pill administration
      for treatment of coronary heart disease].
AB  - OBJECTIVE: To evaluate the effect of long-term Shexiang Baoxin Pill (SXBXP)
      administration on cardiovascular events in patients with stable angina pectoris
      (SAP). METHODS: A prospective randomized non-blind parallel controlled study was
      conducted in the early stage (the first 6 months) of the trial, then a cohort
      study was succeeded in the later stage. Two hundred patients with SAP, who
      visited the hospital between May 2005 and June 2006, were selected and randomly
      assigned to the trial group and the control group, 100 patients in each group.
      Both were treated with conventional therapy, including treatment for anti
      platelet, blood lipid regulating, anti-ischemia, etc, and to patients in the
      trial group, SXBXP was administered additionally for 2 pills, three times a day
      by oral intake. The therapeutic course lasted for at least 6 months. All patients
      were followed up until January 2008, the clinical events and conditions of
      treatment were recorded. The composite terminal of various cardiovascular events
      was regarded as the primary endpoint. RESULTS: The median follow-up time of the
      study was 2.25 years (ranging from 0.5 to 2.75 years). In the trial group, the
      occurrence (cases) was 23 for all-clinical event, 20 for primary-clinical event
      and 9 for angina pectoris event, which were lesser than those in the control
      group, 33, 29 and 19 cases respectively, showing a significant difference between
      groups (P < 0.05). The dosage of nitrates used in the trial was decreased more
      than that before treatment. Besides, all the incidences (cases), in terms of all
      cause death (2 vs 5), cardiovascular death (1 vs 2), congestive heart failure (3
      vs 4), stroke (2 vs 4), and other clinical (5 vs 6) events, as well as in the
      need for percutaneous coronary intervention or coronary artery bypass graft (2 vs
      4), showed somewhat lowering in the trial group as compared with the
      corresponding items in the control group, but statistical analysis showed an
      insignificant difference between them (P > 0.05). CONCLUSION: Long-term SXBXP
      administration could reduce the occurrence of angina pectoris events and some
      other clinical events, and cut down the dosage of nitrates used in patients with
      SAP.

PMID- 20681276
TI  - [Tissue Doppler imaging observation on effect of long-term use of gingko biloba
      tablet on left ventricular function in patients with chronic heart failure].
AB  - OBJECTIVE: To quantitatively observe the effect of long-term use of Gingko biloba
      Tablet (GBT) on left ventricular systolic and diastolic function in patients with
      chronic heart failure (CHF) by tissue Doppler imaging (TDI). METHODS: Eighty-four
      CHF patients were randomly assigned to two groups, the treatment group and the
      control group. All were treated with furosemide, spironolactone, and perindopril,
      but additional medication of GBT was given to the treatment group. The treatment
      lasted for 24 weeks. TDI measurement was performed at three time points, i. e.
      before treatment (T0), 12 weeks and 24 weeks after treatment (T1 and T2), by
      which, the peak velocity on 6 mitral annulus sites at systolic, early and late
      diastolic phase (V(S), V(E), V(A), V(E)/V(A)) was measured, and the average
      velocity on the 6 sites at the 3 phases (V(MS), V(ME), V(ME)/V(MA)) was
      calculated and analyzed. RESULTS: All measured data at T0 were not statistically
      different between the two groups (P > 0.05). As compared with the data measured
      at T0, V(MS), V(ME), V(ME)/V(MA) in the treatment group and V(ME) in the control
      group raised at T2, showing statistical significant differences (P < 0.05).
      Comparisons between groups showed that V(MS), V(ME) at T1 and V(MS), V(ME),
      V(MA), V(ME)/V(MA) at T2 were higher in the treatment group than in the control
      group respectively with statistical significance (P < 0.05 or P < 0.01).
      CONCLUSION: Long-term administration of GBT can significantly improve the left
      ventricular function in CHF patients.

PMID- 20681277
TI  - [Gel electrophoresis analysis on plasma differential protein in patients with
      unstable angina of blood-stasis pattern].
AB  - OBJECTIVE: To seek the plasma differential proteins in patients with unstable
      angina of blood-stasis pattern (UA-BSS) for exploring the proteomic specialty in
      them by way of two-dimensional difference gel electrophoresis (DIGE) detection on
      plasma of patients and healthy persons. METHODS: Using DIGE and tandem mass
      spectrometry, comparative proteomic study was conducted on the plasma of 12 UA
      patients of qi-deficiency and blood-stasis pattern (UA-QBS), 12 UA patients of
      phlegm-stasis cross-blocking pattern (UA-PSS) and 12 healthy volunteers. RESULTS:
      Preliminary results showed that Haptoglobin beta chain, DBP, HBB, HBA,
      Transthyretin, ApoA- I, ApoA-IV were significantly differentially expressed in
      both patterns, while Haptoglobin alpha1 chain, alpha-1-acid glycoprotein, ApoC
      III, ApoA-II, ApoC-II, ApoJ, and Haptoglobin alpha 2 chain were only seen
      differentially expressed in the UA-PSS patients, alpha1-antitrypsin, Fibrinogen
      gamma chain, and Fibrin beta were only seen differentially expressed in UA-QBS
      patients. CONCLUSION: The common proteomics characteristics of patients of QBS
      and PSS patterns may be correlated with inflammatory reaction and metabolic
      disturbance (including blood lipid and blood oxygen).

PMID- 20681278
TI  - [Distribution of Chinese syndrome types in patients with primary osteoporosis and
      its relationship with bone fracture].
AB  - OBJECTIVE: To study the distribution of Chinese syndrome type in patients with
      primary osteoporosis (POP) and its relationship with bone fracture. METHODS:
      Materials of 180 POP patients who visited Xiyuan Hospital were investigated,
      their incidence of bone fracture observed and Chinese syndrome types
      differentiated. And the outcomes were analyzed statistically using SPSS 13.0.
      RESULTS: The morbidity of POP in female was higher than that in male, the sex
      ratio (M/F) being 1:3 (41 cases vs 139 cases). Chinese syndrome type distribution
      in the POP patients was: Shen-deficiency syndrome (SDS) type in 7.8% patients (14
      cases), Pi-Shen deficiency syndrome (PSDS) type in 21.7% (39 cases), Pi-Shen
      deficiency and blood-stasis syndrome (PBS) type in 70.6% (127 cases), the
      difference of partition between types was significant (P < 0.05). Bone fracture
      had occurred in 12.78% (23 cases) of patients, the occurrence in patients with
      different types was 4.34%, 17.39%, and 78.26%, respectively. Incidence of bone
      fracture was also different in patients of various age section, being 5.3% in 50
      59 years section, up to 15.0% in 60-69 years section (P < 0.05), and down to
      12.24% in 70-80 years Section. CONCLUSION: The risk of bone fracture in POP
      patients of PBS type is higher than that in those with SDS or PSDS type, and 60
      69 years is the high risk age section of bone fracture in POP patients.

PMID- 20681279
TI  - [Effect of modified tianxiong powder in treating oligospermia and
      asthenospermia].
AB  - OBJECTIVE: To investigate the clinical efficacy and safety of modified Tianxiong
      Powder (MTP) in treating oligospermia and asthenospermia. METHODS: Eighty
      patients were equally randomized into two groups, the treated group administered
      with MTP, and the controlled group administered with Wuzi Yanzong Pill (WYP), all
      for 3 months. The comprehensive efficacy was observed; and parameters of
      patients' semen and figure of sperm were analyzed before and after treatment.
      RESULTS: The observation was completed in 70 patients. The total effective rate
      and markedly effective rate were 91.43% and 65.71%, respectively in the treated
      group, 85.71% and 54.29%, respectively in the control group, the pregnancy rate
      in their wives was 8.57% and 5.71%, respectively. Comparisons showed no
      statistical significance between groups (P > 0.05). Significant elevated perm
      count in semen and more active sperms with significantly better spermic figure,
      were found in both groups. However, the improvements in the treatment group were
      superior to those in the control group (P < 0.05 or P < 0.01). CONCLUSION: MTP
      shows good efficacy and high safety in treating oligospermia and asthenospermia,
      and it could improve the spermic count, motility and figure, and reduce the head
      deformity rate.

PMID- 20681280
TI  - [Effect of tanshinone II A on the transforming growth factor beta1/Smads signal
      pathway in rats with hypertensive myocardial hypertrophy].
AB  - OBJECTIVE: To investigate the molecular mechanism of tanshinone II A (TSN) for
      preventing left ventricular hypertrophy (LVH) by studying the expressions of
      angiotensin I type 1 receptor (AT1R), transforming growth factor beta1 (TGF
      beta1) and intracellular signal protein gene (Smads gene) in the hypertrophic
      myocardium of hypertensive rat models induced by pressure over-loading. METHODS:
      SD rat model of LVH was established by abdominal aorta constriction. The model
      animals were randomly divided into 4 groups 4 weeks after modeling, the untreated
      model control group (C1), the two tested groups (T1 and T2) treated respectively
      with high (20 mg/kg) and low (10 mg/kg) dose of TSN II A per day via
      intraperitoneal injection, and the positive control group (C2) treated with 10
      mg/kg of Valsartan per day by gastric perfusion, with 8 animals in each group.
      Besides, 8 SD rats managed with sham operation were set up as the sham-operated
      control group (C3) After an 8-week treatment, the caudal arterial pressure, left
      ventricular mass index (LVMI), myocardial fiber dimension (MFD, by pathologic
      examination with HE staining) in rats were measured. Meanwhile, mRNA expression
      of AT1R, protein expression of TGF-beta1 and activity of Smad-3, 4, 7 in the
      ventricular tissue were detected by RT-PCR analysis and Western blotting
      respectively. RESULTS: (1) Blood pressure in Group T1 and T2 was unchanged after
      treatment, which was significantly higher than that in Group C2 and C3 (P < 0.01,
      P < 0.05). (2) LVMI and MFD in Group T1, T2 and C2 were higher than that in Group
      C3 (P < 0.01), but remarkably lower than that in Group C1 (P < 0.01). (3) Levels
      of AT1R, TGF-beta1 and Smad-3 expression increased significantly in the model
      rats (P < 0.01), but they were down-regulated in Group T1 and C2, and the TGF
      beta1 regulating effect in the C2 was more potent than that in Group T1 and T2 (P
      < 0.05). (4) Protein expression of Smad-7 was up-regulated in Group T1, T2 and C2
      obviously (P < 0.01), and the effect in Group T1 was superior to that in C2 (P <
      0.05). CONCLUSION: The myocardial hypertrophy inhibition effect of TSN II A is a
      blood pressure independent process, and it may be related to the inhibition of
      AT1R mRNA expression and blocking of TGF beta1/Smads signal pathway.

PMID- 20681281
TI  - [Effect of yizhi jiannao granule concentration fluid on the differential
      expression protein in entorhinal area tissue of senescence accelerated mouse P8].
AB  - OBJECTIVE: To explore the mechanism of Yizhi Jiannao Granule (YZJN) in treating
      Alzheimer's disease (AD) on proteomic level by analyzing the differential
      expression proteins in entorhinal cortex tissue of senescence accelerated mouse
      P8 (SAMP8) treated with YZJN. METHODS: Six-month old SAMP8 were randomly divided
      into 3 groups, the model group, the YZJN group and the control group, 10 mice in
      each group. The model group was untreated with free water access, the YZJN group
      was treated with concentrated water extract of YZJN 0.3 g per day via gastric
      perfusion, and the control group was perfused with equal volume of double
      distilled water. The total protein in entorhinal cortex tissue of mice was
      extracted after an 8-week treatment with two-dimensional gel electrophoresis, and
      the differential expression protein spots were separated for identification
      through peptide mass fingerprint analysis and database searching. RESULTS: Thirty
      two protein spots expressed differentially between the YZJN group and the model
      group were found, and 14 differential expression proteins were identified,
      including NADH dehydrogenase iron-sulfur protein 6, Rho-GDP dissociation
      inhibitor alpha, beta2-globin, phosphoglyceric kinase, etc, their functions
      involved mitochondria energy metabolism, oxidative stress and neuron function.
      CONCLUSION: YZJN could regulate multiple protein expressions in entorhinal cortex
      tissues of SAMP8, suggesting that it has multi-target therapeutic action and its
      mechanism in treating AD is possibly realized by way of improving mitochondria
      function, antagonizing oxidation stress, preventing nerve cell apoptosis and
      protecting neurons.

PMID- 20681282
TI  - [Effect and mechanism of reserpine for changing salivary protein secretion in Pi
      deficient rats].
AB  - OBJECTIVE: To study the effect of reserpine (RSP) for changing salivary protein
      secretion in Pi-deficient rats and to explore its possible mechanism. METHODS:
      Twenty rats allocated in the RSP group were given subcutaneous injection of RSP
      [0.4 mg/(kg x d)] for 9 successive days, while the other 20 rats in the control
      group were injected with same volume of saline instead. On the 10th day, ten rats
      randomly selected from each group were subjected for extracting saliva to detect
      salivary amylase activity (sAA) before and after an acid stimulation; and drawing
      blood from the orbital vein to measure the contents of vasoactive intestinal
      peptide (VIP) and cyclic adenosine monophosphate (cAMP). Then they were
      sacrificed and their parotids were taken out for pathological examination with HE
      staining, as well as for VIP and cAMP measuring, and zymogen granules counting
      under a transmission electron microscope. The remainder animals were stopped
      injecting and normally fed to 40 days, then subjected to be detected as above
      mentioned. RESULTS: Food intake and body weight reduction were more significantly
      in the RSP group than in the control group. On the 10th day, the ratio of sAA
      before/after stimulation in the RSP group was 0.39 +/- 0.18, significantly lower
      than that in the control group (0.80 +/- 0.21, P < 0.01), but it was restored
      rapidly, reaching the normal range on the 25th day, on the 40th day, it became
      significantly different to the level on the 10th day (P < 0.05) and approached
      the level in the control group (P > 0.05). No significant pathological change of
      parotid was found in both groups; but the number of zymogen granules in the RSP
      group was remarkably more than that in the control group (41.4 +/- 4.9 vs 34.6 +/
      5.2, P < 0.01). Serum level of VIP in the RSP group was significantly less while
      that of cAMP was higher than that in the control group (22.5 +/- 13.1 mg/L vs
      38.5 +/- 14.1 mg/L, and 125.8 +/- 15.5 micromol/L vs 105.3 +/- 16.7 micromol/L,
      both P < 0.05), but no inter-group difference was found in parotid tissue
      contents of both VIP and cAMP. All the indices detected became equivalent in the
      two groups on the 40th day. CONCLUSION: The reduction of salivary protein in Pi
      deficient rats induced by RSP may be related to the regulatory pathway of VIP and
      cAMP.

PMID- 20681283
TI  - [Mechanism of hepatocytes transdifferentiation to bile duct epithelial cells and
      intervention of huangqi decoction].
AB  - OBJECTIVE: To investigate the mechanism of hepatocytes transdifferentiation to
      bile duct epithelial cells (BECs) and intervention of Huangqi decoction (HQD) on
      hepatic fibrosis formation in rats with secondary cholestasis. METHODS: Seventy
      five SD male rats were made into cholestatic hepatic fibrosis model animals by
      bile duct ligation, and randomized into the control group (n = 50) and the HQD
      group (n = 15). Starting from one week after modeling, they were administered
      orally with saline and HQD respectively for four weeks. Besides, a sham-operated
      group was set up with 10 rats operated by choledochus segregating only and
      administered after then with saline. Rats were killed in batches at different
      time points, i.e. each five from the control group and sham-operated group at the
      end of the 1st week, five from the control group for each time at the end of the
      2nd, 3rd and 4th week, and all the remaining rats at the end of the 5th week.
      Their liver tissues were taken for histological change examination, content of
      hydroxyproline (Hyp) determination; protein expression of BECs marker cytokeratin
      7 (CK7) and the hepatocyte specific antigen HepPar detection by Western blot, and
      CK7-Hep Par co-localization by laser confocal microscopy. Then IPP software was
      used to analyze Sirius red stained positive areas of CK7 and Hep Par, as well as
      the average IOD of CK7/Hep Par co-localization. RESULTS: Hepatocytes in hepatic
      tissues (Hep Par positive cell) in the model rats decreased gradually along was
      time went by after modeling (Sham > M1w > M2w > M3w > M4w > M5w), which was in
      parallel with the increase of BECs (CK7 positive cells), degree of fibrosis, Hyp
      content and CK7 protein expression. Increasing of co-localized positive cells of
      CK7/Hep Par began at 1 week and reached the peak 3 weeks after modeling, then it
      decreased gradually. The Hep Par protein expression was negatively correlated
      with that of CK7; the Hep Par positive cell expression was negatively correlated
      with CK7 positive cell expression and collagen deposition; while the CK7 positive
      cell expression was positively correlated with the collagen deposition in the
      liver tissue. Compared with the model control group, the mortality, CK7/Hep Par
      co-localized positive cells, fibrosis degree, Hyp content and CK7 protein
      expression were lesser obviously (P < 0.01), while Hep Par positive cell and
      protein expressions were higher significantly in the HQD group. CONCLUSIONS:
      Hepatocytes transdifferentiation to BECs might be a key pathological element for
      secondary cholestatic hepatic fibrosis formation; the restraining action of HQD
      is possibly a major action mechanism of HQD for effectively intervening and
      treating secondary cholestasis hepatic fibrosis.

PMID- 20681284
TI  - [Effect of yiqi huoxue recipe containing drug-serum on the Toll-Iike receptor-4
      and its downstream signaling components MyD88 as well as the tumor necrosis
      factor receptor related factor-6 in human vein endothelial cells].
AB  - OBJECTIVE: To investigate the influence of Yiqi Huoxue Recipe (YHR) containing
      drug-serum on the expression of Toll-like receptor-4 (TLR4) and its downstream
      signaling components MyD88, as well as the tumor necrosis factor receptor related
      factor-6 (TRAF-6) in human vein endothelial cells (HUVECs) induced by
      lipopolysaccharide (LPS), and to study its possible anti-atherosclerotic
      mechanism from the gene and protein levels. METHODS: Twenty New Zealand male
      rabbits were equally divided into four groups in random: the normal control group
      and the three YHR groups, 5 in each group. They were gastric perfused daily with
      normal saline and YHR in low, moderate and high concentration respectively. Blood
      drawn from rabbits' heart 2 h after ending perfusion on the 7th day, and the
      serum separated (that is the drug-serum) was taken for testing. HUVECs were
      cultured in vitro and equally divided into six groups in random: the normal
      control group, the model group, the Western medicine group and the three YHR
      groups. HUVECs were stimulated with LPS, then treated separately with the drug
      serum containing different concentrations of YHR for 24 h. Then the mRNA
      expressions of TLR4, MyD88 and TRAF-6 were measured with Real-time PCR, and their
      protein expressions were analyzed using Western blotting. RESULTS: Protein and
      mRNA expressions of TLR4, MyD88 and TRAF-6 increased significantly after LPS
      stimulation (P < 0.01), but the changes in the drug-serum treated groups were
      significantly lower than those in the saline control group respectively (P < 0.01
      or P < 0.05). CONCLUSION: YHR can block the high expression of TLR4, and also
      influence the MyD88-dependent signaling pathway of TLR4, suppress the downstream
      expression of NF-kappaB and various related gene expressions, which may be one of
      its mechanisms of action for anti-atherosclerosis.

PMID- 20681285
TI  - [Experimental study on treatment of systemic lupus erythematosus with langchuang
      3 granule].
AB  - OBJECTIVE: To investigate the mechanism of action of Chinese drug Langchuang-3
      Granule (LC-3) in treating systemic lupus erythematosus (SLE) through observing
      its effects on body weight (BW), antinuclear antibody (ANA), spleen index and
      thymus index in BXSB SLE model mice, as well as the deposition of immune complex
      in mice' renal glomeruli. METHODS: SLE model mice were randomized into 4 groups:
      the control group (A), the LC-3 treated group (B), the Western drug treated group
      (C), and the LC-3 combined Western drug treated group (D). BW of mice was
      dynamically observed; spleen index (SI) and thymus index (TI) were measured by
      weighting method; serum anti-ANA level was detected by ELISA; IgG and complement
      C3 in renal glomeruli were analysed by direct immunofluorescence. RESULTS: BW of
      mice remarkably increased after treatment in Group B and D, showing a significant
      difference to that in Group A (P < 0.05). Lower TI level and higher SI level were
      found in the model mice. As compared with Group A, TI was higher in Group B and
      D, SI was lower in Group D, and both indices were lower in Group C (P < 0.05 or P
      < 0.01). Level of ANA decreased (converting from positive to negative) remarkably
      in all the three treated groups (P < 0.01). The fluorescence intensity of IgG and
      C3 in the renal tissue was weaker in Group B, C (both P < 0.05) and D (P < 0.01)
      than that in Group A. CONCLUSION: Both LC-3 and Western medicine showed
      remarkable effects in treating SLE model mice, and the combination of the two
      could display an effect better than that of using either alone.

PMID- 20681286
TI  - [Consensus on Chinese medical diagnosis and treatment of ulcerative colitis
      (2009)].

PMID- 20681287
TI  - [Consensus on Chinese medical diagnosis and treatment of dyspepsia].

PMID- 20681288
TI  - [Some ideas regarding establishment of Chinese medicine clinical assessment
      indices system for studying irritable bowel syndrome].
AB  - Irritable bowel syndrome (IBS) is a commonly seen disease in clinical practice,
      and Chinese medicine shows certain preponderance in treating the disease
      contrasted with modern medicine. However, the clinical effect of Chinese medicine
      was hardly approved by the world, and the lack of widely accepted clinical
      assessment indices (CAI) is an important cause. The establishment of Chinese
      medicine CAI system for studying IBS was discussed in this paper based upon the
      characteristics of clinical effect and clinical assessment of Chinese medicine.

PMID- 20681289
TI  - [Establishing a concise disease-syndrome differentiation and treatment system-
      the primary work for the modernization of Chinese medicine].
AB  - The priority of the modernization of Chinese medicine at present is the
      standardization of Chinese medicine practice, including syndrome differentiation,
      disease diagnosis, standardized therapeutic program, etc. For this reason, the
      primary work is to establish a concise disease-syndrome differentiation and
      treatment system (CDSDTS) under the guidance of Chinese medicine theory, holding
      the core advantages and effectiveness of Chinese medicine, and aiming at creating
      a simplified theoretical and practical program facilitating for operation and
      spreading. It is not a mere simplification or careless reduction, but a
      normalized program of treatment according to the essence of Chinese medicine.
      Although the therapeutic effect might be somewhat lost, it can be widely
      approved, thereby, it would make contributions for the inheritance and
      development of Chinese medicine.

PMID- 20681290
TI  - [The Chinese medicine items of quantifier--their classification, characteristics
      and English].

PMID- 20681291
TI  - [Progress of integrative medical research on deficiency syndrome].

PMID- 20681292
TI  - [Development and structure defense strategies on the fruit of Chaenomeles
      speciosa].
AB  - OBJECTIVE: To study the development rule and structure defense strategies on the
      fruit of Chaenomeles speciosa. METHODS: Anatomical and histochemical methods were
      used to investigate the structure and localization of tannin of the fruit of
      Chaenomeles speciosa. RESULTS: The development of the fruit of Chaenomeles
      speciosa were divided into two periods: cells reproduced rapidly from
      fluorescence to 40 - 50 days after fluorescence, and cells augmented after this.
      The pericarp and seeds were protected by beceptacle which was formed by cuticle,
      epidermis, taniniferous cells layer, parenchyma cells which contained tannin and
      stone cells zones. Tannin was distributed in parenchyma cells of beceptacle
      mostly and in pericarp barely. CONCLUSION: The development and structure of fruit
      of were related with its defense strategies.

PMID- 20681293
TI  - [Germination characters of Polygonum capitatum seed].
AB  - OBJECTIVE: To study the influence of the Polygonum capitatum seed germination by
      different temperatures, cultivating methods and salt stresses, which can provide
      reference for seed germination inspection and field seeding. METHODS: Cultivating
      seeds in Petri dishes and count germination rate. RESULTS: The highest
      germination rate occurs at 15 degrees C; In salt stress condition, with the
      increase of the salt concentration seed germination rate declines and under the
      condition of low salt concentration germination rate shows no obvious difference
      with the controlling group; at the same temperature, germination rate is higher
      when cultivated with light than under dark, and seeds cultured in the filters
      have higher germination rate than those which cultured on the filter. CONCLUSION:
      Germination experiment should carry out at 15 degrees C, with light and between
      paper. Seeds germinate potential should calculate after the germination
      experiment progressing 20 d. When planting, salt concentration of the planting
      seedling field can not above 1 - 2 g/L, otherwise the germination will be
      affected.

PMID- 20681294
TI  - [Transformation of astragaloside IV in bidirectional solid fermenting of
      Astragalus membranaceus].
AB  - OBJECTIVE: To study the transformation of Astragaloside IV in bidirectional solid
      fermenting of Astragalus membranaceus var. mongholicus. METHODS: The chemical
      components of pre and post-fermenting were comparatively analyzed by techniques
      of HPLC, column chromatography and spectral identification. Antioxidant effect of
      transformational product on vascular endothelial cells was researched. RESULTS:
      In fermenting of Astragalus membranaceus, Astragaloside IV was transformed into 6
      O-beta-D-glucoside cycloastragenol, which had significant antioxidant effect.
      CONCLUSION: Biotransformation of Astragaloside IV in Astragalus membranaceus was
      occurred after bidirectional solid fermenting with Ganoderma lucidum, and the
      biotransformation could enhance effect.

PMID- 20681295
TI  - [Study on sequence characterized amplified region (SCAR) markers in Dendrobium
      candidum].
AB  - OBJECTIVE: To establish an effective way for rapid identification of Dendrobium
      candidum based on DNA molecular marker. METHODS: The genetic diversity among 11
      wild species of Dendrobium was studied by using the random amplification
      polymorphism DNA. The special segment with random primer in Dendrobium candidum
      was recovered, cloned and sequenced. According to its sequence, a pair of
      specific primers was synthesized and tested for the specific detection of
      Dendrobium candidum. RESULTS: The results of PCR showed that only a 302 bp
      electrophoresis band of Dendrobium candidum named DS-302 was found. According to
      the result of sequence analysis in the Genbank databases, no distinct
      comparability was found. And a specific primer was designed and used to identify
      Dendrobium candidum from other Dendrobium species effectively. There was a same
      band like DS-302 in Dendrobium candidum, but not be discovered in other species
      of Dendrobium. CONCLUSIONS: The RAPD marker DS-302 was successfully converted
      into SCAR marker. It was an effective way to identify Dendrobium candidum more
      rapidly.

PMID- 20681296
TI  - [Studies on NACE-DAD fingerprint of Cortex Phellodendri].
AB  - OBJECTIVE: To establish the analytical method for the fingerprint of Cortex
      Phellodendri by NACE-DAD and estimate the quality of Cortex Phellodendri from
      different habitats and species. METHODS: Based on the mode of nonaqueous
      capillary electrophoresis, 40 mmol/L sodium acetate and 40 mmol/L ammonium
      acetate methanol solution was selected for the buffer (pH 5.8). The separation
      voltage was 25 kV and detection wavelength was set at 210 nm. Berberine was used
      as a reference standard, the chromatographic fingerprint was determined. The data
      were analysed by Fuzzy Cluster and Fingerprint Similarity Evaluation Software to
      compare the similarity of samples. RESULTS: NACE-DAD fingerprints with 9 common
      peaks were established preliminarily. It was discovered that a small number of
      samples differed from others. Regarding to the fingerprints of Cortex
      Phellodendri and its processed products, there were obvious differences in the
      relative areas of common peaks. CONCLUSION: The method is reliable, accurate and
      can be used for quality control of Cortex Phellodendri.

PMID- 20681297
TI  - [Comparison of pharmacological effects of Fructus Mume and its processed
      products].
AB  - OBJECTIVE: To compare the pharmacological effects of Fructus Mume and its
      processed products, to investigate pharmacologic relation among Fructus Mume,
      malic acid, citric acid. METHODS: Blood glucose from orbital sinus was measured
      to observe the effects of Fructus Mume, Fructus Mume sarcocarp and Fructus Mume
      carbon, malic acid, citric acid on blood glucose level of normal mice. The
      efficacy of drugs above on gastrointestinal motility was investigated through
      coated charcoal method in small intestinal propulsive motion in mice.
      Antimicrobial spectrum and minimal inhibitory concentrations for drugs were
      obtained by antimicrobial tests in vitro. RESULTS: Fructus Mume, Fructus Mume
      sarcocarp, Fructus Mume carbon and malic acid could enhance intestinal propulsive
      motion and motility in percentage. Fructus Mume sarcocarp and Fructus Mume
      carbon, malic acid and citric acid could reduce the level of blood glucose in
      normal mice. Fructus Mume, Fructus Mume sarcocarp and Fructus Mume carbon, citric
      acid and malic acid showed an inhibitory effect on growth of Staphylococcus
      aureus, Escherichia coli, Pseudomonas aeruginosa, Monilia albican to a certain
      extent. CONCLUSION: Pharmacological functions of Fructus Mume are not exactly the
      same with its products. Thus, in order to achieve safety during drug application,
      they should be administrated base on diagnosis. Because malic acid and citric
      acid in Fructus Mume show a correlation with its pharmacological actions, they
      can be used as parameters for quality control standard.

PMID- 20681298
TI  - [Fingerprint analysis of Dipsacus asperoides by HPLC].
AB  - OBJECTIVE: To establish the HPLC fingerprints of Dipsacus asperoides for
      reflecting the internal information, evaluating its internal quality. METHODS: 20
      batches of D. asperoides were collected from different place with the HPLC
      fingerprints method. Chromatographic column: Welchrom-C18 (250 mm x 4. 6 mm, 5
      microm), mobile phase: acetonitrile and water (gradient elution), flow rate: 1.0
      mL/min, detection wavelength: 212 nm, column temperature: 35 degrees C. RESULTS:
      The common mode of HPLC fingerprint was established and similar degrees to D.
      asperoides from different areas were compared. CONCLUSION: The method is stable,
      reliable, and with full information which can be used for quality evaluation,
      quality control item and crude drug identification of D. asperoides.

PMID- 20681299
TI  - [Studies on the chemical constituents of Balaophora polyandra].
AB  - OBJECTIVE: To study the chemical constituents of Balaophora polyandra. METHODS:
      The chemical constituents were isolated by column chromatography on silica gel,
      Toyopearl HW-40C and Sephadex LH-20. Their structures were elucidated on the
      basis of spectral analysis. RESULTS: 8 compounds have isolated from this plant,
      and the structure of them have identified as Gallic acid (1), Ellagic acid (2),
      Ferulic acid (3), Caffeic acid (4), p-hydroxylcinnamic acid (5), 1,3-di-O-galloyl
      4,6-(S) - hexahydroxydiphenyl-beta-D-glucopyrannose (6),1-O-(E) - caffeoyl- 3-O
      galloyl-beta-D-glucopyrannose (7), 2-O-(E) - caffeoyl-1-O-[see symbol] - (E) -
      coumaroyl-beta-D-glucopyrannose (8). CONCLUSION: Compounds 1 - 8 are isolated
      from this plant for the first time.

PMID- 20681300
TI  - [Studies on the chemical constituents of Ligularia macrophylla].
AB  - OBJECTIVE: To study the chemical constituents of Ligularia macrophylla. METHODS:
      Isolation and purification were carried out on repeated silica gel column
      chromatography. The structures of the compounds were identified by physico
      chemical properties and spectral analyses. RESULTS: Eight compounds were isolated
      and identified as kaempferol (1), 2,4'-dihydroxy-5-methoxychalcone (2), 5-hydroxy
      3,4', 7-trimethoxyflavone (3), isobutyl ester terephthalic acid (4), 4
      hydroxybenzaldehyde (5), mono (2-ethylhexyl) terephthalate (6), lupeol (7), beta
      sitosterol (8). CONCLUSION: Compounds 1 - 7 are isolated from this plant for the
      first time.

PMID- 20681301
TI  - [Studies on the chemical constituents from aerial parts of Gynura divaricata].
AB  - OBJECTIVE: To study the chemical constituents from aerial parts of Gynura
      divaricata. METHODS: The constituents were isolated on silica gel column
      chromatography, preparative TLC and Sephadex LH-20 column chromatography,
      identified by physicochemical properties and the structures were elucidated by
      spectral analysis. RESULTS: 10 compounds were isolated and identified as 2-(1',
      2', 3', 4'-tetrahydroxybutyl)-6-(2", 3", 4"-trihydroxybutyl)-pyrazine (1), 2-(1',
      2', 3', 4'-tetrahydroxybutyl)-5-(2", 3", 4"-trihydroxybutyl) -pyrazine (2),
      nicotinic acid (3), 5-hydroxy-picolinic acid(4), methyl-5-hydroxy-2-
      pyridinecarboxylate (5), adenosine (6), uridine (7), stigmasterol-5-O- beta-D
      glucoside (8), dibutyl terephthalate (9), methyl chlorogenate (10). CONCLUSION:
      Compounds 1, 2, 5, 9, 10 are obtained from this genus for the first time,
      Compounds 3, 4 are obtained from this plant for the first time.

PMID- 20681302
TI  - [Studies on the polysaccharide SGPS2 from the fruits of Siraitia grosvenorii].
AB  - OBJECTIVE: To study the structure of the polysaccharides constituents in the
      fruits of Siraitia grosvenorii (Swingle) C. Jeffrey. METHODS: SGPS2 was purified
      by DEAE-cellulose and Sephadex G-200 column chromatography, the component and
      structure of SGPS2 were analyzed on the basis of spectral and chemical studies by
      HPLC, IR analysis, partial hydrolysis with acid, methylation analysis, GC and 13C
      NMR. RESULTS: The molecular weight of SGPS2 was 650 000. Polysaccharide was
      composed of L- made up of (1 --> 2, 4) linked rhamnose, (1 --> 4) linked rhamnose
      residues in main chain; and (1 --> 2) linked rhamnose, (1 --> 3) linked rhamnose
      in side chains. Terminal residues attached main chain to rhamnose. CONCLUSION:
      SGPS2 was composed of rhamnose and curonic acid.

PMID- 20681303
TI  - [Studies on the chemical constituents of Teyou 2 Folium Mori].
AB  - OBJECTIVE: To study the chemical constituents of Teyou 2 Folium Mori. METHODS:
      The compounds were extracted and isolated by CO2 supercritical fluid extraction,
      30% alcohol extraction, macroporous resin and silica gel column chromatography
      and their structures were elucidated by means of melting point, TLC and spectral
      analyses. RESULTS: Six compounds were identified as beta-carotene (I), oleanolic
      acid (II), benzoic acid (III), chlorogenic acid (IV), lysine (V), gamma
      aminobutyric acid (VI). CONCLUSION: Compound II and V are isolated from this
      plant for the first time.

PMID- 20681304
TI  - [Analysis of the chemical constituents of essential oil from the leaves of
      Callicarpa integerrima].
AB  - OBJECTIVE: To analyze the compositions of the essential oil from the leaves of
      Callicarpa integerrima. METHODS: GC-MS method was used. RESULTS: 42 chemical
      constituents, accounting for 97.62% of total content were identified. CONCLUSION:
      The main components were beta-caryophyllene (33.74%), Elixene (12.86%), tau
      Cadinene (9.57%) and (-) -Spathulenol (8.99%). Besides, some sesquiterpenes and
      their oxides, such as Copaene (4.21%), Globulol (3.81%), alpha-Caryophyllene
      (2.48%), 2-Naphthalenemethanol, decahydro-alpha, alpha, 4a-trimethyl-8-methylene
      [2R-(2alpha, 4aalpha, 8alphabeta)]-(2.37%) and 1,6-Cyclodecadiene (2.24%) had
      also relatively high contents.

PMID- 20681305
TI  - [Analysis of the chemical constituents of essential oil from Chimonanthus
      zhejiangensis by GC-MS].
AB  - OBJECTIVE: To analyze the chemical constituents of the essential oil from
      Chimonanthus zhejiangensis. METHODS: Steam distillation was employed to extract
      volatile compounds of essential oil from Chimonanthus zhejiangensis. Volatile
      compounds of essential oil were isolated and identified by capillary GC-MS-DS.
      RESULTS: 37 components were separated and 33 components were successfully
      identified. CONCLUSION: The main components were 1,4-Cineole (46.20%), 1,5,9
      Undecatriene, 2,6, 10-trimethyl-, (Z)-(9.71%), Cyclohexane, 3,4-bis (1
      methylethenyl) -1, 1-dimethyl-(7.42%), Trioctylamine (6.44%), alpha-Terpinyl
      propionate (4.01%), alpha-Pinene (3.92%).

PMID- 20681306
TI  - [Protective and therapeutic effects of schisandrol A on Abeta damaged PC12
      cells].
AB  - OBJECTIVES: To observe the protective and therapeutic effect of schisandrol A on
      the Abeta damaged PC12 cells. METHODS: PC12 cells were damaged by Abeta in vitro.
      Morphological changes were observed and the number of cells with neurite was
      analyzed by phase contrast microscope. The cell viability of PC12 cells was
      determined by the MTT method. RESULTS: Many dispirited cells with atrophied or
      fragmented neurites in the Abeta damaged PC12 cells were observed under the
      microscope. More vital cells with longer neurites were observed in the
      schisandrol A treated PC12 cells and the number of cells with neurite increased.
      The difference of cell viability between the two groups was statistical
      significant. CONCLUSION: Schisandrol A can antagonize the neurotoxicity of Abeta
      and has protective and therapeutic efficacy on Abeta damaged PC12 cells.

PMID- 20681307
TI  - [Inhibitory effect of Jiawei Sanleng pill medicated serum on estrogen production
      and its influence on apoptosis of human endometrial cells of endometriosis].
AB  - OBJECTIVE: To study the inhibitory effect on estradiol (E2) production of
      endometriosis by medicated serum of Jiawei Sanleng pill (SLW) and approach the
      mechanism of inducing apoptosis of human endometrial cells of endometriosis by
      medicated serum of SLW. METHODS: The eutopic endometrial cells of hysteromyoma
      and endometriosis patients were cultured. Taking that of the endometrial cells of
      hysteromyoma as control, the secretion level of E2 of endometrial cells in the
      culture media supernatant at different time point with the treatment of high,
      middle and low dose of SLW serum was detected by electrochemiluminescence
      immunoassay and the apoptosis percentage of endometrium cells in early stage and
      late stage was detected by flow cytometry and TUNEL method. After the optimal
      time for SLW to induce apoptosis of eutopic endometrial cells of endometriosis in
      early stage and late stage was identified based on time-effect relationship,
      another endometrium cells were divided into six groups: hysteromyoma endometrium
      group, eutopic endometrium of endometriosis group, eutopic endometrium of
      endometriosis + middle dose of SLW serum group, eutopic endometrium of
      endometriosis + anastrozole serum group, eutopic endometria of endometriosis +
      middle dose of SLW serum + E2 group and eutopic endometrium of endometriosis + E2
      group. The apoptosis percentage of endometrial cells in early stage and late
      stage of each group was detected according to the optimal time point
      respectively. RESULTS: The secretion level of E2 of eutopic endometrium of
      endometriosis was decreased by SLW, which showed the dependence of concentration
      and time. The apoptosis percentage of endometrial cells in hysteromyoma
      endometrium group in early stage and late stage was increased along with the time
      and they was significantly higher than that of eutopic endometrium of
      endometriosis group at the same time point (P < 0.05 or P < 0.01). After 72 hours
      and 96 hours, with the treatment of middle dose of SLW serum, the apoptosis
      percentage of eutopic endometrial cells of endometriosis in early stage and late
      stage was 35.67 +/- 1.73 and 57.56 +/- 1.09 respectively, and the effect of
      inducing apoptosis was significantly stronger than that of the other time point.
      After 72 hours, with the combined treatment of middle dose of SLW serum and 5.30
      ng/L E2, or after 96 hours, with the combined treatment of middle dose of SLW
      serum and 6. 36 ng/L E2, the apoptosis percentage of eutopic endometrial cells in
      early stage and late stage was decreased to 11.25 +/- 2.00 and 7.72 +/- 0.71
      respectively, which had significant difference with that of middle dose of SLW
      serum group (P < 0.01). The apoptosis of the eutopic endometrial cells of
      endometriosis was induced by medicated serum of SLW could not be completely
      counteracted by E2 add-back treatment. Just with the treatment of 5.30 ng/L or
      6.36 ng/L E2, the apoptosis percentage of eutopic endometrial cells of
      endometriosis in early stage and late stage tended to decrease, but there was no
      statistical significance (P > 0.05). Anastrozole, a specific aromatase inhibitor,
      had the contrary action to E2. CONCLUSION: SLW could decrease the secretion of E2
      so as to induce apoptosis of the eutopic endometrial cells of endometriosis.

PMID- 20681308
TI  - [Effects of artemisinin on proliferation, apoptosis and Caspase-3 expression of
      rat mesangial cell].
AB  - OBJECTIVE: To study the effects of artemisinin on proliferation, apoptosis and
      Caspase-3 active of rat mesangial cell. METHODS: Rat mesangial cells were
      incubated with different concentrations of artemisinin, the proliferation,
      apoptosis and Caspase-3 active of rat mesangial cell were measured by MTT assay,
      fluorescent inverted microscope and enzyme-labeled analytical instruments
      respectively. RESULTS: Compared with control group, the proliferation and Caspase
      3 expression of mesangial cell of three other groups were significantly different
      (P < 0.01). Compared with dexamethasone group, there were significant difference
      effects of proliferation and Caspase-3 expression of mesangial cell in other two
      groups of identical concentration drugs (P < 0. 01), especially in the
      artemisinin + glucocorticoid (ArtGC) group, and the effects of three different
      drugs on the mesangial cell Caspase-3 expression, proliferation and apoptosis had
      the tendency of depend on dosage, and mass mortality of mesangial cell in the
      mediate-dosage and high-dosage ArtGC group. CONCLUSION: Artemisinin could inhibit
      the proliferation of mesangial cell, enhance the expression of Caspase-3 and
      promote the apoptosis in a dose-dependent manner.

PMID- 20681309
TI  - [Effects of deer tendons collagen on osteoporosis rats induced by retinoic acid].
AB  - OBJECTIVE: To study the effects of deer tendons collagen on osteoporosis rats
      induced by retinoic acid. METHODS: Male Wistar rats were randomly divided into
      normal control group, model control group, deer tendons collagen high, medium and
      low-dose groups, osteoporosis rats of retinoic acid-induced were set up. Changes
      of body weight, bone weight, bone mineral density, bone histomorphometry, plasma
      phosphorus, calcium, alkaline phosphatase (ALP), bone mechanics were measured
      before and after treatment of deer tendons collagen. RESULTS: Compared with model
      control group,after treated by deer tendons collagen, body weight, bone mineral
      density, bone weight was increased in varying degrees, bone histomorphometry
      parameters were significantly different, the ALP in plasma was significantly
      reduced, contents of Ca, P were increased, all indicators of bone mechanics were
      significantly higher. CONCLUSION: Deer tendons collagen can prevent and treat
      retinoic acid-induced osteoporosis of rats.

PMID- 20681310
TI  - [Protective effect of extractive of Dioscorea zingiberensis against
      ischemia/reperfusion injury in cultured neonatal rat cardiomyocytes].
AB  - OBJECTIVE: To define the structure of a water-soluble compound (SY-A) extracted
      from Dioscorea zingiberensis and investigate its protective effect against the
      neonatal rat cardiomyocytes ischemia/reperfusion (I/R) injured. METHODS: The SY-A
      was isolated from Dioscorea zingiberensis by utilizing column chromatograph and
      its structure was identified by 1H-NMR, 13C-NMR, 135DEPT. Neonatal rat
      cardiomyocytes were cultured and divided into 5 groups randomly. Then a model of
      ischemic/reperfusion (I/R) was established. Cells were divided into control
      group, simulated ischemia/reperfusion group (I/R group), I/R + SY-A (50 mg/L)
      group, I/ R + SY-A (100 mg/L) group and I/R + SY-A (150 mg/L) group. The levels
      of malondialdehyde and Creatine Kinase were measured. The cell viability was
      determined by MTT assay. RESULTS: The structure of SY-A was identified as 4
      methoxybenzoic acid-2-O-glucopyranoside. Compared with I/R group, the levels of
      LDH and CK were decreased significantly in the SY-A group, and the cell viability
      was increased obviously. CONCLUSION: Extractive of Dioscorea zingiberensis showed
      protective effect against the neonatal rat cardiomyocytes ischemia/reperfusion
      injured.

PMID- 20681311
TI  - [Optimization on preparation of hawthorn fruit total flavonoids-phospholipid
      complex using Plackett-Burman design, central composite design and response
      surface methodology].
AB  - OBJECTIVE: To choose the optimal conditions for the formation of the complex with
      total flavonoids in hawthorn fruit and phospholipid. METHODS: Solvent evaporation
      process was used to prepare hawthorn total flavonoids phospholipid complex. The
      evaluation criterion was the complex ratio. The experiment inspected the
      significance of influential factor of preparation technology by Plackett-Burman
      design and optimized significance of factor and level with the central composite
      design. The binomial and linear equations were fitted to the data of overall
      desirabilities, and the resulting equation was used to produce 3-D response
      surface graphs, through which the optimal formulation was predicted. RESULTS: The
      ratio of total flavonoids to phospholipid, flavonoids concentration and reaction
      temperature had significant influence on the craft. It was showed that the
      correlation coefficient of second-order quadratic model was high. The correlation
      coefficient reached 0.9886. The optimum conditions for the preparation of the
      complex were as follows: phospholipids/total flavonoids was 3 : 1, the
      temperature was 40 degrees C and the concentration of principal agent was 10
      mg/mL The deviation between the result of the best craft verification test and
      the binomial fitting equation forecast value was less than 2.0%. CONCLUSION:
      Response surface methodology is successfully used to optimize the preparation of
      total flavonoids in hawthorn phospholipid complex. The optimized process is
      reliable, stable and available for the industrial production.

PMID- 20681312
TI  - [Optimal extraction of effective constituents from Aralia elata by central
      composite design and response surface methodology].
AB  - OBJECTIVES: To optimize the process of extracting effective constituents from
      Aralia elata by response surface methodology. METHODS: The independent variables
      were ethanol concentration, reflux time and solvent fold, the dependent variable
      was extraction rate of total saponins in Aralia elata. Linear or no-linear
      mathematic models were used to estimate the relationship between independent and
      dependent variables. Response surface methodology was used to optimize the
      process of extraction. The prediction was carried out through comparing the
      observed and predicted values. RESULTS: Regression coefficient of binomial
      fitting complex model was as high as 0.9617, the optimum conditions of extraction
      process were 70% ethanol, 2.5 hours for reflux, 20-fold solvent and 3 times for
      extraction. The bias between observed and predicted values was -2.41%.
      CONCLUSION: It shows the optimum model is highly predictive.

PMID- 20681313
TI  - [Enzymatic production of oral nutritional liquid from oyster].
AB  - OBJECTIVE: To prepare an oral nutritional liquid for protecting liver and
      antialcoholic from defatted oyster powder. METHODS: The orthogonal design was
      used to determine the optimal enzymatic hydrolytic condition and the enzymolysis
      liquid from oyster was deodorized and seasoned. RESULTS: The optimum hydrolytic
      conditions were determined as follows: defatted oyster powder added concentration
      of 2%, ratio of enzyme to base material 10%, enzymatic hydrolytic time 90 min,
      temperature 50 degrees C, pH 6.2. The content of glycogen, crude protein and
      amino acids in the oral nutritional liquid were 461 mg/100 mL, 381 mg/100 mL and
      294.5 mg/100 mL, respectively. CONCLUSIONS: The processing conditions are stable
      and reliable and can be used to provide reference for further pilot scale
      production.

PMID- 20681314
TI  - [Preparation study of total lactone of Ginkgo controlled release pellet].
AB  - OBJECTIVE: To study the preparation technique of total lactone of Ginkgo
      controlled release pellet. METHODS: Aquacoat as controlled release material, DBS
      as plasticizer, HPMC as diffusion promoter, the best manufacture technique was
      got according to the factors affecting the release of the pellet. RESULTS: The
      controlled release pellet had good release rate and achieved the aim of
      controlling release. CONCLUSION: The technique could be used for
      industrialization production.

PMID- 20681315
TI  - [Study on self-microemulsifying drug delivery system of LianXiang prescription].
AB  - OBJECTIVE: To prepare self-microemulsifying drug delivery system (SMEDDS) of
      LianXiang prescription. METHODS: After the test of solubility for the initial
      screening, surfactants and cosurfactants with certain oil phase were screened
      through the study of ternary phase diagram and in accordance with the size of
      self-microemulsifying areas; To screen and optimize the self-microemulsifying
      formulation, the influence of related factors such as the ingredients of the
      prescription and dilution media on the self-microemulsifying areas were tested,
      and the particle dimension of microemulsion was determined. The tests of self
      microemulsifying rate and stability were carried out to evaluate the formulation.
      RESULTS: The total alkaloid of Coptis chinensis--the essential oil of Eugenia
      caryophyllata-Cremophor RH60-1,2-propylene glycol(40: 20: 60: 20, w/w) was the
      optimal formulation; it had good self-microemulsifying efficiency and stability,
      and its microemulsion had smaller particle dimension and polydispersity index
      (17.4 nm, 0.176). CONCLUSION: The optimal formulation can be used as SMEDDS of
      LianXiang prescription for follow-up researches.

PMID- 20681316
TI  - [Formula screening and optimizing for the dispersible tablets of breviscapine by
      orthogonal experiment].
AB  - OBJECTIVE: To establish a suitable formulation for the dispersible tablets of
      brevisicapine. METHODS: To prepare and optimize the breviscapine dispersible
      tablets by orthogonal experiment design using disintegration time as the index.
      The quality of breviscapine dispersible tablets was evaluated by the initial
      stability test. RESULTS: The disintegration time of optimized prescription
      formulation was 89 s. L-HPC and CMS-Na were used by combining exterior and
      interior and the dissolution percent in vitro was obviously superior to the
      conventional tablets, and the quality of the dispersible tablets was very good in
      stability test. CONCLUSION: The formulation screened out for the dispersible
      tablets of breviscapine is reasonable, stable and suitable for the production on
      a large scale.

PMID- 20681317
TI  - Biology and applications of mesenchymal stem cells.
AB  - Undifferentiated adult stem cells are responsible for cell replacement in adult
      organisms. Initially isolated from the bone marrow, they are now known to be
      distributed throughout the organism as a whole, with a perivascular location.
      They are defined by properties which include proliferation as adherent cells, a
      defined immunophenotype, and the capacity to differentiate in vitro into
      osteoblasts, adipocytes and chondroblasts. Mesenchymal stem cells (MSCs) are
      considered as one of the most promising cell types for therapeutic applications.
      Mechanisms responsible for this therapeutic role are not well understood, and may
      involve diferentiation or, as most evidences point out, paracrine activity. The
      ability to modulate the immune system opens a wide range of applications, mainly
      for autoimmune diseases and graft-versus-host disease. Preclinical and clinical
      studies show promising results, but controversial results are still reported,
      indicating the need for further basic and preclinical investigation on their
      therapeutic potential. This review will focus on recent advances in understanding
      MSC biology and applications in cell therapy.

PMID- 20681318
TI  - Mesenchymal stem cells as a platform for gene therapy protocols.
AB  - Mesenchymal stem cells (MSCs) are considered as the adult stem cells with the
      greatest therapeutic potential, due to characteristics such as plasticity,
      intrinsic tropism towards lesions, paracrine activity, and immunosuppressive
      activity. This potential may be optimised by transforming them with genes which
      will improve their therapeutic ability or are therapeutic by themselves. This
      review presents a summary of the main types of viral or plasmid vectors used to
      transform therapeutic MSCs and their use in different pathologies. Although this
      strategy holds great promise, results are still heterogeneous, showing that more
      studies are needed to optimise gene transfer methods and models.

PMID- 20681319
TI  - Organ transplantation has come of age.
AB  - Organ transplantation started in the mid-1950s with a kidney transplant between
      identical twins, demonstrating the surgical technique could provide successful
      therapy. The immunological barrier to be overcome, however proved to be far more
      difficult to deal with. The introduction of immunosuppressive agents produced
      some success but it was not until Cyclosporin became available in the 1980s that
      results became sufficiently good for widespread acceptance and rapid development
      of organ grafting. Now with more powerful and selective agents, although there is
      still much room for improvement in immunosuppression, one of the main problems in
      organ transplantation is a result of its success, namely a shortage of organ
      donors. In this review, I summarise these matters.

PMID- 20681321
TI  - Natural products from the hallucinogenic sage.
AB  - The isolation, structures and biological activity of the neoclerodane and other
      natural products obtained from the Mexican hallucinogenic sage, Salvia divinorum
      are reviewed.

PMID- 20681320
TI  - Development and regeneration of projection neuron subtypes of the cerebral
      cortex.
AB  - The idea of repairing damaged neuronal circuitry in the mammalian central nervous
      system (CNS) has challenged neuroscientists for centuries. This is mainly due to
      the notorious inability of neurons to regenerate and the unparalleled cellular
      diversity of the nervous system. In the mammalian cerebral cortex, one of the
      most complex areas of the CNS, multipotent neural stem and progenitor cells
      undergo progressive specification during development to generate the staggering
      variety of projection neuron subtypes that are found in the adult. How is this
      process orchestrated in the embryo? And, can developmental signals be used to
      regenerate projection neuron subtypes in the adult or in the dish? Here, we first
      provide an overview of the diversity and fate potential of neural progenitors of
      the cerebral cortex during development. Further, we discuss the plasticity of
      neural progenitors and the roles of intrinsic and extrinsic signals over
      progenitor fate. Finally, we discuss the relevance of developmental signals for
      efforts to direct the differentiation of pluripotent stem cells into specific
      types of cortical projection neurons for therapeutic benefit.

PMID- 20681322
TI  - Plant poisons: their occurrence, biochemistry and physiological properties.
AB  - Plants produce poisons as a defence against predators. Many of these substances
      are biosynthesised from non-protein amino acids by biosynthetic pathways which
      have been deduced from the results of isotopic tracer analysis. These secondary
      metabolites have been used by humans over thousands of years, both as drugs and
      as agents to kill animals and commit homicide.

PMID- 20681323
TI  - Effects of age and soccer expertise on general tests of perceptual and motor
      performance among adolescent soccer players.
AB  - This study of perceptual and motor skills in soccer players was conducted on
      adolescent males. The goals were to monitor the development of general perceptual
      motor skills in nonsoccer-playing and soccer-playing groups (n = 245), to examine
      the relationship between physical maturity and general perceptual motor skills (n
      = 41), and to compare the differences in general perceptual motor skills between
      groups with different soccer expertise (n = 142). The measured variables were
      simple reaction time, peripheral awareness, eye-hand-foot coordination, and
      testosterone blood level. The results suggested that general perceptual motor
      skills improved with age, the development of these skills was related to
      participants' blood testosterone concentration (especially between 12 and 14
      years), and general perceptual motor skills improved with soccer expertise.
      However, the differences between subelite and elite soccer players were not
      meaningful enough to encourage practitioners to test general perceptual motor
      skills on a large scale when evaluating the potential of young players.

PMID- 20681324
TI  - Nonselective access of phonological lexicon for two different orthographies:
      Korean and English.
AB  - In studies of bilingual word processing, the primary question has been
      [corrected] whether various bilingual lexical information is selectively or
      nonselectively activated. [corrected] Specifically, when a reader processes a
      [corrected] second language, the lexical properties of the first language can
      influence the processing of the second language, or vice versa. Phonological
      priming was significant for both target languages with 50 msec. duration of the
      priming presentation. [corrected]

PMID- 20681325
TI  - Perceived tiredness and heart rate variability in relation to overload during a
      field hockey World Cup.
AB  - The aim of the study was to examine the utility of perceived tiredness to predict
      cardiac autonomic response to overload among field hockey players during the 2006
      World Cup. The French Society for Sports Medicine (SFMS) questionnaire was
      administered at the start of the Cup to evaluate perception of tiredness.
      Autonomic function was assessed nine days later at the semifinal match by time
      and frequency domain analysis of heart rate variability. An anxiety questionnaire
      was administered so that the effect of precompetitive anxiety on heart rate
      variability could be controlled. Results showed a negative correlation between
      perceived tiredness scores and time domain indexes, and a positive correlation of
      perceived tiredness scores and the high frequency component ratio (LF/HF ratio)
      of heart rate variability. Anxiety did not influence the precompetitive cardiac
      response despite somatic anxiety's correlation with sympathetic response (LF/HF
      ratio) and tiredness scores. Perceived tiredness predicted the autonomic cardiac
      response to competitive overload. Thus, the perceived tiredness assessment would
      be a good early marker of fatigue and overload states during competition.

PMID- 20681326
TI  - Sex differences in relations of muscle power, lung function, and reaction time in
      athletes.
AB  - In an earlier study, relations of nonverbal abilities with several bodily
      measures such as height, weight, and lung capacity were observed. The present aim
      was estimation of associations of muscle power and lung function with simple eye
      hand reaction time. Sex differences for muscle power were significant even with
      the covariates of height, weight, and age included; however, these disappeared
      for lung functions (forced vital capacity and peak expiratory flow) and reaction
      time. The effects of leg power, forced vital capacity, and peak expiratory flow
      on the left eye-hand reaction time were significant after adjustment for height,
      weight, right- and left-hand powers and age. The positive effect of exercise may
      be especially associated with the right brain activity or left hand speed.

PMID- 20681327
TI  - Race performance in male mountain ultra-marathoners: anthropometry or training?
AB  - The association of anthropometric variables, training volume, and prerace
      experience with race time was investigated in 25 male mountain ultra-marathoners
      (M age = 44.5 yr., SD = 7.0; M body mass = 73.0 kg, SD = 7.8; M body height =
      1.78 m, SD = 0.07; M Body Mass Index = 22.9 kg/m2, SD = 1.8) in a 7-day mountain
      ultra-marathon over 350 km with a total 11,000 m of altitude gained and lost. The
      relationship of anthropometry (body mass, body height, Body Mass Index, percent
      body fat, circumferences of limbs, and thicknesses of skin-folds), training, and
      prerace experience (years as active runner, average training volume in hours and
      kilometres per week, average running speed in training, and personal best time in
      marathon running) with total race time was investigated using bivariate
      correlation analysis. None of the variables of anthropometry were related to
      total race time. Average speed in running during training and personal best time
      in marathon running were associated with total race time. Speed in running during
      training was correlated with personal best time in marathon running. The finding
      that average speed in running during training and personal best marathon time
      were related to race performance suggests that training and especially intensity
      might be of increased importance in these ultra-runners compared to
      anthropometry.

PMID- 20681328
TI  - Chunking and compound cueing of movement sequences: learning, retention, and
      transfer.
AB  - When teaching a complex sequence, the sequence is often chunked into components;
      however, this strategy may not always benefit learning, but may be detrimental.
      The hypothesis is that this occurs because chunking deprives learners of compound
      cues that could aid recall. To test this, participants learned 9-item movement
      sequences, either as three 3-item chunks or as one 9-item series. To undermine
      compound cueing, some sequences had several movements in common. Learning a
      sequence in chunks impaired motor skill acquisition only when participants could
      have exploited compound cues; it also led participants to adopt an alternative
      recall strategy, which transferred to novel sequences even though this was
      detrimental to recall.

PMID- 20681329
TI  - Examining differences between center of pressure sway in one-legged and two
      legged stances for soccer players and typical adults.
AB  - To examine stance during the measurement of balance ability, this study aimed to
      clarify the differences and relationships between balance ability in one-legged
      (dominant or nondominant leg) and two-legged stances in 25 typical male adults
      and 25 male soccer players. Balance ability was evaluated with four sway factors:
      sway velocity, anterior-posterior sway, lateral sway, and high-frequency sway
      factors. The one-legged stance was more unstable than the two-legged stance, the
      balance abilities related to two-legged and one-legged stances differed, and the
      balance abilities related to dominant-legged and nondominant-legged stances were
      similar. The one-legged stance, which was difficult to maintain stably, may be
      useful in the measurement of static balance ability in young people.

PMID- 20681330
TI  - Comparison of perceived exertion ratings during graded peak cycle exercise
      between cigarette smokers and nonsmokers.
AB  - This study compared differentiated Ratings of Perceived Exertion (RPE) for the
      chest (RPE-Chest) and legs (RPE-Legs) and undifferentiated ratings (RPE-Overall)
      between cigarette smokers (n = 10) and nonsmokers (n = 10) during graded, peak
      cycle exercise. Linear regression analyses expressed RPE-Chest, RPE-Leg, and RPE
      Overall as a function of VO2 for smokers and nonsmokers. RPE equivalent to 50,
      70, and 90% VO2 peak were compared between. Chest, Leg, and Overall RPE were
      similar at each % VO2 peak. In the combined smokers and nonsmokers, RPE-Chest was
      lower (p < .05) than the RPE-Overall at each % VO2 peak. RPE-Leg did not differ
      from RPE-Overall at 50% VO2 peak, but was higher (p < .05) at 70% and 90% VO2
      peak. These results validate Assumption 4 for application of the Borg 15-category
      scale in that this assumption is also valid for differentiated RPE. Smoking did
      not influence the intensity of differentiated or undifferentiated RPE during
      graded cycle exercise.

PMID- 20681331
TI  - Validity of St. George's Respiratory Questionnaire for Greek patients with
      chronic obstructive pulmonary disease.
AB  - The purpose of the present study was to examine the validity of St. George's
      Respiratory Questionnaire (SGRQ), a disease-specific survey of health-related
      quality of life, in adult Greek patients with chronic obstructive pulmonary
      disease (COPD). Questionnaire scores, dyspnea scores, spirometry values, and
      demographic data were collected from 72 patients with a diagnosis of COPD
      exacerbation. Follow-up visits were performed at 1-mo. intervals for the first 3
      mo. after discharge and a final visit was performed 6 mo. after discharge. 27
      (37.5%) patients were readmitted during the follow-up period. Recovery after
      exacerbation was prolonged and questionnaire scores were sensitive to the
      patients' health-status changes across time. The SGRQ discriminated COPD patients
      according to disease stage, and the SGRQ scores during the recovery course were
      related to readmission. Correlations between the SGRQ and % FEV1 were not
      significant during exacerbation but a significant negative correlation was
      observed during the stable phase of the disease. The SGRQ appeared to have
      acceptable discriminant and concurrent validities in Greek COPD patients who
      differed according to their exacerbation stage.

PMID- 20681332
TI  - Initial body mass index and free-time physical activity moderate effects of the
      Youth Fit for Life treatment in African-American pre-adolescents.
AB  - In about 80% of youth obesity-prevention programs, significant decrease in Body
      Mass Index has not been observed. A meta-analysis of 16 trials of the 12-wk.
      Youth Fit For Life intervention suggested better success; however, the effects
      for children who were overweight or obese remain unclear because data from
      participants of all weights were aggregated. Also unclear were effects on
      increasing free-time physical activity, a goal of this and most obesity
      prevention treatments. Of the 200 African American pre-adolescents assessed in
      the present investigation, reductions in Body Mass Index associated with Youth
      Fit For Life were larger for participants who were overweight and obese, but
      these two groups did not differ. Voluntary physical activity at baseline was
      inversely related to change in voluntary physical activity (r = -.53, p < .001).
      Regression analyses suggested improvements in theoretical dimensions of self
      efficacy significantly predicted increases in voluntary physical activity
      especially well for participants initially classified as insufficiently active
      (R2 = .61). These data clarified and extended findings to date for the Youth Fit
      For Life treatment, but replications across age groups, ethnicities, and
      administration formats are required.

PMID- 20681333
TI  - Differences in spatial working memory as a function of team sports expertise: the
      Corsi Block-tapping task in sport psychological assessment.
AB  - Individual differences in visuospatial abilities were investigated in experienced
      basketball players compared with nonathletes. Most research shows that experts
      and novices do not differ on basic cognitive ability tests. Nevertheless, there
      are some equivocal findings indicating there are differences in basic cognitive
      abilities such as attention. The goal of the present research was to investigate
      team-ball athletes in regard to their visuospatial abilities. 112 male college
      students (54 basketball players, 58 nonathlete college students) were tested in
      their spatial capacity with the Corsi Block-tapping Task. No differences in
      spatial capacity were evident between basketball players and nonathlete college
      students. The results are discussed in the context of the expert performance
      approach and individual difference research.

PMID- 20681334
TI  - Sex differences in effects of testing medium and response format on a
      visuospatial task.
AB  - Sex differences on visuospatial tests are among the most reliably replicated. It
      is unclear to what extent these performance differences reflect underlying
      differences in skills or testing factors. To assess whether testing medium and
      response format affect visuospatial sex differences, performances of introductory
      psychology students (100 men, 104 women) were examined on a visuospatial task
      presented in paper-and-pencil and tablet computer forms. Both sexes performed
      better when tested on paper, although men outperformed women. The introduction of
      an open-ended component to the visuospatial task eliminated sex differences when
      prior spatial experiences were controlled, but men outperformed women when prior
      spatial experiences were not considered. In general, the open-ended version and
      computerized format of the test diminished performance, suggesting that response
      format and medium are testing factors that influence visuospatial abilities.

PMID- 20681335
TI  - Biomechanics and motor control of normal young adults performing a wheelchair
      wheelie balance task.
AB  - The purpose of the present study was to describe kinetically and kinematically
      the control patterns of wheelchair wheelies, to clarify the relation between
      motion of the wheelchair and floor reaction force, to reveal movement strategies
      of the task, and to find useful parameters to understand the control and learning
      process of the skill. 10 healthy female Japanese students who were able to
      perform a 2-min. stationary wheelie participated in the experiments. Analysis of
      the 20-sec. wheelie performances suggested that (1) Center of Pressure is not a
      fundamental parameter for wheelie balance control, but may be the result of the
      control (2) the anteroposterior component of the floor reaction force is a
      fundamental parameter for analyzing the control of a wheelchair wheelie, and (3)
      angular velocity is used in the control of wheelie balance as a cue.

PMID- 20681336
TI  - Effect of progressive self-focus meditation on attention, anxiety, and depression
      scores.
AB  - This study evaluated the effects of Progressive Self-focus Meditation with 42
      volunteers (M age = 46.0 yr., SD = 14.1) allocated to two groups: one that had
      weekly 1-hr. training sessions in the practice for 5 wk. and one waiting-list
      group. Participants were evaluated before and after 5 wk. on the Beck Anxiety
      Inventory, Beck Depression Inventory, the Digit Symbol subtest of the Wechsler
      Adult Intelligence Scale, and the Mindfulness Attention Awareness Scale. After 5
      wk., a significant reduction in scores on depression was found in the Meditation
      group as well as an increase in attention in comparison with the waiting-list
      Control group.

PMID- 20681337
TI  - The effect of deliberate play on tactical performance in basketball.
AB  - This field-based study analyzed effects of a deliberate-play training program in
      basketball on tactical game intelligence and tactical creativity. 22 youth
      basketball players, ages 10 to 12 years, completed basketball training in one of
      two equal-sized groups. The deliberate-play training program contained
      unstructured game forms in basketball. The placebo group played in traditional
      structured basketball game forms. Tactical intelligence and creativity was
      assessed before and after an 18-lesson intervention. Analysis showed significant
      training improvement only for the deliberate-play group. In addition, this
      outperformance of the placebo group was not only observed for tactical creativity
      but also for tactical intelligence.

PMID- 20681338
TI  - Effects of Stroop interference on categorical perception in simultaneous color
      discrimination.
AB  - Two experiments were conducted to assess the effects of verbal interference on
      categorical perception. The task involved simultaneous color discrimination with
      no memory demands, and a concurrent Stroop task was employed as verbal
      interference. Exp. 1 demonstrated that categorical perception was eliminated by
      an incongruent color word (i.e., Stroop interference), but not by a congruent
      color word or nonword fixation crosses. Exp. 2 demonstrated that categorical
      perception decreased when the intensity of Stroop Interference was increased, and
      it increased when correct verbal coding was enhanced. These results provide
      further evidence that interfering with verbal coding disrupts categorical
      perception, suggesting that verbal coding has a crucial role in categorical
      "perception." It is also suggested that categorical perception could occur at the
      encoding or decision level but not at the storage or memory level. The possible
      mechanisms for categorical perception are also discussed.

PMID- 20681339
TI  - Coincidence-anticipation timing and reaction time in youth tennis and table
      tennis players.
AB  - The purpose of this study was to compare the coincidence-anticipation timing and
      reaction times (RT) of 10- to 14-year-old tennis and table tennis players and
      examine possible sex differences. 107 (51.4%) tennis and 101 (48.6%) table tennis
      players participated in this study. Players were compared on coincidence
      anticipation timing and reaction time. Tennis players performed with less error
      in the coincidence-anticipation timing task than table tennis players, whereas
      table tennis players had lower mean reaction time than tennis players. It was
      also found that male players made fewer errors in the coincidence-anticipation
      timing task than their female counterparts.

PMID- 20681340
TI  - Mental practice and the retention of motor learning: a pilot study.
AB  - This study compared the effects of mental practice, physical practice, and no
      practice on the performance and retention of a novel throwing task. Research
      supports the effectiveness of mental practice on performance; however, retention
      of learning has not been adequately investigated. Participants were 152 students
      ages 18 to 44 years (M = 20.5, SD = 2.9), who completed a pretest, posttest, and
      five-week delayed retention test of dart throwing with the nonpreferred hand. In
      the practice phase, participants completed 50 mental practice or physical
      practice trials of the darts task or 50 trials of a catching task. Results
      indicated that overall scores increased from pretest to posttest and retention
      test, and decreased from posttest to retention test, but that these effects did
      not differ for type of practice. The findings suggest equal learning and
      retention of learning for novel throwing tasks for control, mental practice, and
      physical practice conditions; however, further research that considers issues
      raised is recommended.

PMID- 20681341
TI  - Hand dominance and grip strength of older Asian adults.
AB  - Hand dominance in a group of Asian adults 60 to 89 years old was examined.
      Participants were independently living in the community; free of pain, injury,
      and disease of the upper limbs; and had no restrictions on use of upper
      extremities in daily activities. The grip strengths of both hands were measured
      with a Jamar hand dynamometer. Analysis showed that being male, of younger age,
      and using the dominant hand were significantly associated with stronger grip than
      being female, of older age, and using the nondominant hand. The dominant to
      nondominant grip ratio varies from 1.05 to 1.10 across age-sex subgroups.

PMID- 20681342
TI  - Motor schema development in constant practice: the gradient in bimanual juggling
      with three balls.
AB  - Motor schemas are very attractive concepts; however, their development and
      internal structure appear difficult to probe and identify. The present study
      focuses on the development of a motor schema in constant practice. In four
      experiments, participants practiced bimanual juggling with three standard balls.
      During retention tests they were asked to juggle with standard ("practiced")
      balls and nonstandard ("nonpracticed") balls of different weight, shape, length,
      and size. Four juggling experiments were carried out. The participants achieved
      the best results juggling with the practiced balls in three experiments. During
      one experiment, they achieved better results juggling with nonpracticed balls.
      However, in all four experiments, a correlation was observed between the number
      of correct juggling sequences with standard balls and with nonpracticed balls.
      Scores presented as mean numbers of juggling cycles performed in retention tests
      revealed a gradient with its peak value for juggling with the practiced balls. In
      one experiment, the hypothetical gradient slope was steeper; however, a strong
      correlation between scores for juggling with practiced and nonpracticed balls was
      noted.

PMID- 20681343
TI  - Anthropometric characteristics and motor skills in talent selection and
      development in indoor soccer.
AB  - Kick performance, anthropometric characteristics, slalom, and linear running were
      assessed in 49 (24 elite, 25 nonelite) postpubertal indoor soccer players in
      order to (a) verify whether anthropometric characteristics and physical and
      technical capacities can distinguish players of different competitive levels, (b)
      compare the kicking kinematics of these groups, with and without a defined
      target, and (c) compare results on the assessments and coaches' subjective
      rankings of the players. Thigh circumference and specific technical capacities
      differentiated the players by level of play; cluster analysis correctly
      classified 77.5% of the players. The correlation between players' standardized
      measures and the coaches' rankings was 0.29. Anthropometric characteristics and
      physical capacities do not necessarily differentiate players at post-pubertal
      stages and should not be overvalued during early development. Considering the
      coaches' rankings, performance measures outside the specific game conditions may
      not be useful in identification of talented players.

PMID- 20681344
TI  - Effects of shape, size, and chromaticity of stimuli on estimated size in normally
      sighted, severely myopic, and visually impaired students.
AB  - Effects of shape, size, and chromaticity of stimuli on participants' errors when
      estimating the size of simultaneously presented standard and comparison stimuli
      were examined. 48 Taiwanese college students ages 20 to 24 years old (M = 22.3,
      SD = 1.3) participated. Analysis showed that the error for estimated size was
      significantly greater for those in the low-vision group than for those in the
      normal-vision and severe-myopia groups. The errors were significantly greater
      with green and blue stimuli than with red stimuli. Circular stimuli produced
      smaller mean errors than did square stimuli. The actual size of the standard
      stimulus significantly affected the error for estimated size. Errors for
      estimations using smaller sizes were significantly higher than when the sizes
      were larger. Implications of the results for graphics-based interface design,
      particularly when taking account of visually impaired users, are discussed.

PMID- 20681345
TI  - The effects of advertisement location and familiarity on selective attention.
AB  - This study comprised two experiments to examine the distracting effects of
      advertisement familiarity, location, and onset on the performance of a selective
      attention task. In Exp. 1, familiar advertisements presented in peripheral vision
      disrupted selective attention when the attention task was more demanding,
      suggesting that the distracting effect of advertisements is a product of task
      demands and advertisement familiarity and location. In Exp. 2, the onset of the
      advertisement shortly before, or after, the attention task captured attention and
      disrupted attentional performance. The onset of the advertisement before the
      attention task reduced target response time without an increase in errors and
      therefore facilitated performance. Despite being instructed to ignore the
      advertisements, the participants were able to recall a substantial proportion of
      the familiar advertisements. Implications for the presentation of advertisements
      during human-computer interaction were discussed.

PMID- 20681346
TI  - Caregivers' perceptions of clothing for people with severe and profound
      intellectual disabilities.
AB  - This exploratory study inquires into the role fashionable clothing plays in the
      normalization process and others' perceptions of people with severe and profound
      intellectual disabilities. The research was conducted with a sample of 10
      caregivers. Fashionable clothing and attention to grooming are perceived to aid
      the normalization process and help facilitate positive perceptions from others.
      Poor grooming and clothing that is ill-fitting, out of fashion, or dirty hinder
      the normalization process and likely influence negatively others' perceptions of
      persons with severe and profound intellectual disabilities.

PMID- 20681347
TI  - Speech rate treatments for individuals with dysarthria: a tutorial.
AB  - Research confirms the long-standing clinical observation that patients with
      dysarthria exhibit variability in speech rate. Thus, modifying speech rate has
      been documented as one of the best treatment options for these patients. In this
      tutorial, several published rate control interventions for dysarthric speakers
      are presented. Studies discussed utilized various interventions, including pacing
      boards, alphabet board supplementation, visual and auditory feedback, cueing and
      pacing strategies, and delayed auditory feedback. Interventions discussed
      represent a hierarchy from "rigid" strategies, which impose maximal rate control,
      to techniques allowing for greater speech naturalness and independent rate
      control. All procedures are examined with respect to effectiveness in reducing
      rate, effect on intelligibility and prosody, training requirements, specific
      alterations made to speech rate, and other relevant aspects.

PMID- 20681348
TI  - Skilled basketball players rotate their shoulders more during running while
      dribbling.
AB  - The relationship between running velocity and trunk rotation during normal
      running and running while dribbling was investigated in 7 male competitive
      basketball players and 7 male nonplayers. Participants performed a normal 20-m
      sprint and a 20-m sprint while dribbling a basketball. For the motion analysis,
      all individuals also performed normal running and running while dribbling at
      target of their maximal speed of sprinting and dribbling, respectively.
      Basketball players showed significantly smaller decreases in their running
      velocity from 85% maximal (target) sprint to 85% maximal (target) dribbling
      speeds than nonplayers. Furthermore, basketball players rotated their shoulders
      significantly more during target dribbling than during target running. For all
      participants, significant positive correlations were found between the decreases
      in running velocity and shoulder rotation. The results suggested that the
      basketball players' greater shoulder rotation during dribbling permits their
      running velocity to decrease less during target dribbling compared to a maximal
      sprint.

PMID- 20681349
TI  - [Evaluation of tobacco addiction among adolescents and its treatment within the
      health care].
AB  - Evaluation and treatment of tobacco addiction among adolescents require partly
      different means than those for adults. Some adolescents are hooked already from
      the first cigarettes. Indicators of dependence designed for adults and based on
      regular smoking are suitable for daily smoking adolescents. Indicators providing
      a more sensitive detection of the appearance of the first signs of dependence are
      suitable for the less smoking. Regular meetings enabling an open discussion
      within personal or group councelling constitute the main components in the
      treatment of tobacco addiction in adolescents. Preliminary evidence exists also
      on the efficacy of supplementary nicotine patches and bupropion.

PMID- 20681350
TI  - [Metagenomics opens up new frontiers in microbiology].
AB  - Metagenomics can be described as genomics of all the microorganisms in a
      community. In recent years it has been applied to the study of microbial
      communities in soil and in human intestine, as an example. In metagenomics the
      microbial communities can be linked to their ecological roles and functions. Not
      only the species present in a sample are detected but the microbial communities
      are studied based on the whole genetic material. Thus novel genes, proteins and
      biochemical pathways are discovered. The sequencing technologies have developed
      rapidly within last years and this has enabled the study of genomes and
      metagenomes of individual organisms and whole communities, respectively, in
      reasonable time and with decreasing expenses.

PMID- 20681351
TI  - [Treatment of cleft lip and palate in Finland].
AB  - In Finland about 120 babies are born with cleft lip and palate per year. The
      largest group is those with isolated cleft palate (60%) and only one fourth have
      complete cleft lip and palate. The clefts are closed under one year of age.
      Clefts affect appearance, occlusion and speech and the final outcome can only be
      assessed at the end of the growth. Centralisation of services and a
      multidisciplinary team approach has a bigger influence on the final outcome than
      different treatment protocols, the comparative advantages of which remain
      unproven. Good documentation is important to assess the level of treatment
      outcomes.

PMID- 20681352
TI  - [New methods for dietary counselling in Finland].
AB  - The observed poor adherence to dietary guidelines is in contrast with their
      relatively well-known content. Emphasis in psychosocial factors that enhance
      motivation and self-reliance on dietary counselling could improve the situation.
      In Finland, three new counselling methods have recently become available.
      "Neuvokas" is a tool for maternity clinics, enabling easy follow-up of family
      health behaviour. "Painokas" is a tool-kit that helps in broaching the subject of
      family health behaviour and resources and motivation. In "Taste School", children
      are offered food-derived stimulus for their senses. With these new tools, the
      emphasis on counselling is changed from sharing information to the self-reliant
      use of information. Families need empowering support and inspiring experiences of
      healthy food. One's diet is not chosen, it is learned during childhood.

PMID- 20681353
TI  - [Abdominal compartment syndrome].
AB  - Elevated intra-abdominal pressure causes functional disturbances for the
      cardiovascular system, respiration, kidneys and the intestinal tract. Causes
      underlying the abdominal compartment syndrome include in most cases a major
      abdominal operation, severe abdominal trauma, pancreatitis, burn injury or
      sepsis. The diagnosis is based on the measurement of intra-abdominal pressure by
      using a urinary catheter. As the first-line treatment, attempts are made to
      decrease the volume of abdominal contents, with a concomitant optimisation of the
      patient's hemodynamics. If the pressure is not adequately lowered or the
      condition progresses, the abdominal cavity is opened, the abdominal walls are
      left open and later closed.

PMID- 20681354
TI  - [Treatment of obsessive-compulsive disorder in an adult].
AB  - Obsessive-compulsive disorder is a common, chronic and functionally
      incapacitating psychiatric disorder characterized by obsessive thoughts and
      compulsive acts. First-line drug therapy utilizes serotonin reuptake inhibitors
      at dosages that are usually higher and yield slower responses than those used in
      the treatment of major depression. Second generation antipsychotics or
      haloperidol may also be beneficial. Merely behavioral and/or cognitive
      psychotherapy may be applied in mild and moderate cases, whereas a combination of
      different forms of therapy is the most effective treatment in severe forms.

PMID- 20681355
TI  - [Strong metatarsal pain and localized bone lesions in a physically active male
      (clinico-pathological conference report)].
AB  - With the exception of a previous history of pulmonary sarcoidosis, a previously
      healthy 38-year old man developed a sudden unilateral metatarsal pain and
      gradually progressing osteoporotic, partly lytic metatarsal bone lesions. The
      patient received a bisphosphonate treatment. Clinical and radiological situation
      began to improve during the follow-up observation. The diagnosis was based on
      clinical picture.

PMID- 20681356
TI  - [Are brief intervention recommendations feasible?].
AB  - Primary health care contacts are a suitable arena to reduce patients' risky
      drinking. We studied whether the clinical guidelines are followed and thus
      considered feasible by nurses and physicians. A naturalistic material in Helsinki
      primary health care was collected in 2006-2008. Most professionals participated
      giving information on 18000 primary health care patients, of whom 56% had
      fulfilled the AUDIT-test. Most risky drinkers (AUDIT > or = 8) were given advice,
      80% even booklets or other material, as recommended in the guidelines. Thus,
      brief intervention recommendations, including the use of the AUDIT, seem to be
      feasible in primary care settings.

PMID- 20681357
TI  - [Insulin-induced lipoatrophy in children].
AB  - Insulin-induced lipoatrophy is a rare but serious complication of insulin
      treatment. Its incidence decreased during 1970' and 1980's, but several reports
      of this phenomenon have again recently been published. Traditional treatment
      options have included injecting insulin or pump cannula to the area surrounding
      the lipoatrophy or changing the insulin type or preparation. In this report we
      present 4 children who developed severe lipoatrophy during insulin pump
      treatment. Changing injection sites did not help but lipoatrophy disappeared in
      one patient after changing the insulin preparation. In the three other patients
      no new atrophy sites have appeared after change in insulin preparation or
      simultaneous treatment with local pimecrolimus or sodium cromoglicate.

PMID- 20681358
TI  - [Update on current care guidelines: treatment of alcohol abuse].
AB  - Brief intervention is an effective form of treatment for excessive alcohol
      consumption prior to the development of dependency. Motivational interviewing and
      cognitive therapy are likely to increase the effectiveness of treatment. Another
      effective method is the Twelve-Step Facilitation treatment programme. Supervised
      disulfiram medication significantly improves the results achieved with
      psychosocial therapies alone. Naltrexone increases the number of non-drinking
      days and reduces relapses compared with a placebo, especially if the medication
      is combined with psychosocial treatment which is based on cognitive behaviour
      therapy. Compared with a placebo, acamprosate improves the treatment results
      achieved with psychosocial therapies alone.

PMID- 20681359
TI  - Current Belgian adenotonsillectomy practice: a survey among Belgian ENT
      specialists.
AB  - OBJECTIVES: Tonsillectomies and adenotonsillectomies (TE and ATE) are among the
      most frequently performed operations in the western world. Despite the lack of
      generally accepted clinical guidelines about indications, the beneficial role of
      the procedure has been established. The aim of this study was to identify current
      practice relating to indications for tonsillectomies and adenotonsillectomies
      among Belgian ENT specialists. METHODS: An anonymous questionnaire was sent to
      all Belgian ENT specialists. Part I of the questionnaire included questions about
      the ENT specialist himself/herself and his/her practice. Part II comprised
      questions about indications for TE/ATE in children up to 16 years of age. Part
      III included questions about indications in adults. RESULTS: 238 out of 528
      questionnaires were completed and returned. The majority of physicians consider
      TE/ATE to be indicated if a child or an adult suffers 3 or 4 tonsillitis episodes
      per year. The decision to operate on children for upper airway obstruction is
      mainly based on clinical and anamnestic findings. A peritonsillar abscess is
      usually considered to be an indication for surgery. We compared the results
      between different groups of ENT specialists and could detect differences in
      decision-making only according to the number of years of ENT practice. The
      stringency of surgeons' indications decreases with increasing surgeon age.
      CONCLUSIONS: The majority of respondents consider
      tonsillectomies/adenotonsillectomies to be indicated after 3 to 4 episodes of
      tonsillitis per year. In the case of upper airway obstruction in children,
      surgical indications are mainly based on clinical and anamnestic findings.
      Surgical decision-making appears to be influenced by the number of years of ENT
      practice.

PMID- 20681360
TI  - Is the pathological examination of routine tonsillectomy and adenoidectomy
      specimens necessary? A retrospective study of 559 adenoidectomy and 1132
      tonsillectomy specimens and a literature review.
AB  - OBJECTIVE: There is still no consensus about the necessity of histopathological
      analysis of routine tonsillectomy and adenoidectomy specimens. In this study, our
      goal was to determine the incidence of unexpected pathological findings in
      routine tonsillectomy and adenoidectomy specimens. The results are discussed in
      the light of current literature. MATERIALS AND METHODS: The patient data were
      obtained from the archives of the departments of otorhinolaryngology and
      pathology. Between November 1992 and July 2006, chronic, recurrent infections or
      obstructive problems led to bilateral tonsillectomies, adenoidectomies, and
      adenoidectomies plus tonsillectomies being performed in 435, 502, and 770
      patients respectively. Five hundred and fifty-nine of 1272 adenoidectomy
      specimens and 1132 of 2410 tonsillectomy specimens were sent to the department of
      pathology for histopathological examination. RESULTS: The histopathological
      results for all the adenoidectomy specimens reported chronic inflammatory
      processes. Only one of 1132 tonsillectomy specimens involved granulomatous
      inflammation, while 1131 were chronic inflammatory processes. CONCLUSION: On the
      basis of the result of our study and review of the published literature, the
      microscopic analysis of routine tonsillectomy and/or adenoidectomy specimens may
      not be necessary, especially in young patients with no clinically suspicious
      factors for malignancy. However, all patients must be carefully examined for
      evidence of malignancy before surgery.

PMID- 20681361
TI  - Outcome of sleep endoscopy in obstructive sleep apnoea: the Antwerp experience.
AB  - OBJECTIVES: Snoring and obstructive sleep apnoea (OSA) result from upper airway
      (UA) collapse during sleep. Sleep endoscopy is a dynamic evaluation of the UA
      that can be used to determine the site(s) of collapse during respiratory events.
      This study evaluates the feasibility and outcome of sleep endoscopy in patients
      with OSA, compares the findings with the literature, and reviews the therapeutic
      advice given to patients. METHODOLOGY: A retrospective analysis was conducted of
      the data for 70 OSA patients in whom UA surgery was considered. Sleep endoscopy
      was performed after IV administration of midazolam and propofol. The UA was
      visualised and assessed for the location of UA flutter, narrowing or collapse.
      Feasibility and safety were evaluated retrospectively. Outcome data were
      described as type and pattern of flutter and/or collapse. Treatment advice given
      to the patients was reviewed. RESULTS: Sleep endoscopy showed monolevel palatal
      collapse in 31.9%, monolevel tongue/hypopharyngeal collapse in 27.8% and
      multilevel collapse in 31.9% of patients. In 5.6% of patients, no collapse was
      found. In all patients except 2, reliable assessment proved possible of the
      site(s) of obstruction. No side effects were reported. CONCLUSION: Sleep
      endoscopy is feasible and safe in daily practice when sedation is performed by an
      anaesthesiologist and can be used to locate the site of collapse in the UA. Sleep
      endoscopy findings in our study sample, as well as in the literature, differ
      according to the content of the study sample and the method of sedation.
      Treatment advice may differ from sleep endoscopy findings since other factors
      such as age and patient preferences need to be considered.

PMID- 20681362
TI  - A new oxidative stress marker in patients with nasal polyposis: advanced
      oxidation protein products (AOPP).
AB  - OBJECTIVES: The aim of this study was to determine whether levels of advanced
      oxidation protein products (AOPP) can be used a marker of oxidative stress in the
      etiology of nasal polyposis. MATERIALS AND METHODS: Twenty-four patients
      diagnosed with nasal polyposis in Haseki Education and Research Hospital ENT
      Department between March and June 2008 were included in the study. The AOPP serum
      levels in NP patients and 24 healthy controls were measured with
      spectrophotometry and the results were compared statistically. RESULTS: AOPP
      levels were significantly higher in the study group compared with the control
      group. CONCLUSION: Our findings suggest that AOPP levels can be used as a marker
      of oxidative stress in patients with nasal polyposis. Future studies are
      neccessary to evaluate the efficacy of antioxidant therapy.

PMID- 20681363
TI  - Clinical outcomes of sinonasal inverted papilloma surgery. A retrospective study
      of 67 cases.
AB  - BACKGROUND: Endoscopic sinus surgery has become popular for the management of
      sinonasal inverted papillomas (IP). OBJECTIVE: The purpose of this report is to
      review our 13 years of experience in managing IPs. METHODS: Retrospective chart
      study. Sixty-seven patients with sinonasal IPs were treated in our department
      from 1991 to 2004. Seventeen were managed using an endonasal non-endoscopic
      approach, 39 endoscopically, 8 through external techniques, and the remaining 3
      using a combined approach. RESULTS: After 1994, as we gained experience using
      endoscopic sinus surgery, most cases were treated endoscopically. In only 3
      cases, where the tumour attachment site was in the lateral / anterior wall of the
      maxillary sinus and in the lateral wall of the frontal sinus, could the lesions
      not be accessed by extended endoscopic techniques, and an appropriate combination
      with external methods was required. The mean follow up period was 91 (range, 36
      146) months. The recurrence rate was 59% using an endonasal non-endoscopic
      approach, 12.5% using an external incision, and 12.8% using endoscopic
      techniques. Average time to recurrence was 15 months. CONCLUSION: Our findings
      suggest that endoscopic sinus surgery for sinonasal IP is a viable approach, with
      a low rate of recurrence and minor morbidity. Complete tumour resection at the
      site of attachment, including a surrounding rim of normal mucosa and drilling the
      underlying bone, is the key to successful treatment when it is combined with the
      preservation of healthy tissue. Non-endoscopic endonasal surgery is no longer a
      treatment option because the recurrence rate is too high.

PMID- 20681364
TI  - Postparotidectomy facial nerve paralysis: peripheral versus proximal
      identification.
AB  - OBJECTIVES: Facial nerve palsy is a distressing complication of parotid surgery.
      We determined to analyse parotid surgery outcomes in a district general hospital
      in order to identify our own risk factors leading to increased incidence of
      facial nerve palsy. Primarily, we aimed to determine the efficacy of peripheral
      versus proximal facial nerve identification in preventing facial nerve damage.
      METHODS: This was a retrospective study of hospital records. The records of sixty
      four patients aged between 32 and 84 years who had attended our Otolaryngology
      department over a six-year period were analysed, with notes made of operative
      procedure, identification of the facial nerve and post-operative facial nerve
      palsy. The Neurosign400 facial nerve monitor was used and the degree of facial
      nerve paralysis was assessed using the House Brackmann (HB) classification of
      facial nerve paralysis. RESULTS: Sixty-four patients underwent parotidectomy.
      Thirty-two patients had the peripheral branch of the facial nerve identified
      while another thirty-two patients had proximal nerve identification. Six patients
      had HB 2 facial nerve palsy, but all completely recovered within six months. Four
      out of the six patients had peripheral identification of the facial nerve.
      CONCLUSIONS: Although peripheral versus proximal identification of the facial
      nerve was associated with greater incidence of temporary facial nerve paralysis,
      all the patients recovered within six months. This study may indicate that
      exposing a peripheral branch of the facial nerve with the help of Neurosign400 is
      a useful way of performing parotidectomy where proximal identification of a nerve
      is not possible.

PMID- 20681365
TI  - Otoscopic findings in hypercholesterolemic subjects.
AB  - OBJECTIVES: We aimed to verify the extent of a previously cited relationship
      between tympanosclerosis and atherosclerosis by investigating subjects with
      dysfunction in lipid metabolism but no clinically apparent symptoms of
      atherosclerotic disease. METHODOLOGY: Forty hypercholesterolemic patients were
      submitted to Doppler ultrasound examination of carotid and vertebrobasilar
      arterial regions; results were matched to otoscopic findings. Otoscopy was
      performed to evaluate for sclerotic plaques of the tympanic membrane, which
      represent the most common, clinically non-relevant manifestation of
      tympanosclerosis. A control group of 41 randomly chosen healthy subjects were
      also included. RESULTS: Nine (22.5%) of 40 subjects with hypercholesterolemia
      showed tympanic sclerotic plaques at otoscopy compared to 2 (4.9%) out of 41
      control patients. This difference was statistically significant (p = 0.02). An
      even stronger association (p = 0.01) was found between tympanic and arterial
      plaques in the study group, as we identified tympanic sclerotic plaques in 7
      (41.2%) out of 17 patients with positive Doppler ultrasound signals for arterial
      plaques. Only two (8.7%) out of 23 subjects without plaques on Doppler ultrasound
      examination had tympanic sclerotic plaques. CONCLUSIONS: The results of this
      study confirm the existence of a link between tympanosclerosis and
      atherosclerosis. To our knowledge, this is the first report of a link between
      these findings in preclinical atherosclerotic conditions.

PMID- 20681366
TI  - Cavernous hemangioma of the external ear: case report and literature review.
AB  - OBJECTIVES: To describethe occurrence of a cavernous hemangioma of the external
      auditory meatus extending to the middle ear and the retroauricolar region in an
      adult patient, and to review the relevant literature. METHODS: Case report. We
      report the clinical presentation, imaging studies and surgical procedures used in
      the study. RESULTS: The angiographic study showed that the blood supply of the
      mass originated from the posterior auricular artery. Via a retroauricular
      approach, this artery was isolated and ligated in order to control the intra
      operative bleeding. A canal wall up mastoidectomy with posterior tympanotomy and
      a tympano-canaloplasty were performed, permitting a complete excision. At 36
      months of follow-up, no clinical and radiological signs of recurrence were
      detected. CONCLUSION: Surgical removal is the treatment of choice, with rare
      recurrence of the hemangiomas. Pre-operative evaluation is based on computed
      tomography (CT scan), but should be followed by magnetic resonance angiography
      (MR-angio) or intra-arterial digital subtraction angiography (IA-DSA), especially
      in case of wider lesions.

PMID- 20681367
TI  - Nodular fasciitis of the external auditory canal.
AB  - PROBLEM: Nodular fasciitis (NF) is a reactive myofibroblastic proliferation that
      may be misdiagnosed as a sarcoma because of its rapid growth, rich cellularity,
      and mitotic activity. NF is uncommon in the auricular region. We describe a case
      of nodular fasciitis of the external auditory canal in an 8-year-old male.
      METHODOLOGY: An excisional biopsy was performed, and the pathologic examination
      was consistent with nodular fasciitis; however, the lesion recurred within a
      month requiring that a total excision be done. RESULTS: The patient is without
      recurrence 7 months after the total excision. CONCLUSIONS: Because its histologic
      features closely mimick a malignant lesion, NF must be considered in the
      differential diagnosis of a mass originating from the external auditory canal to
      avoid overly aggressive and functionally debilitating treatment.

PMID- 20681368
TI  - Wegener's granulomatosis of the temporal bone and skull base that mimicked an
      inflammatory myofibroblastic tumour: a case report.
AB  - OBJECTIVE: To compare two potential diagnoses of a temporal bone pseudotumour: an
      inflammatory myofibroblastic tumour and Wegener's granulomatosis. METHODOLOGY: A
      case of Wegener's granulomatosis that mimicked an inflammatory myofibroblastic
      tumour is reported. The clinical presentation, staging of the disease, histology,
      and follow-up are analysed. RESULTS: Histopathology of the temporal bone failed
      to provide an accurate diagnosis, even after immunocytochemical analyses. The
      diagnosis of Wegener's granulomatosis was suspected after biopsy of a pulmonary
      mass and was confirmed by the presence of anti-neutrophil cytoplasmic antibodies
      in blood samples. CONCLUSION: Irrespective of the aetiology, a pseudotumour of
      the temporal bone should always be investigated by biology and radiology.
      Radiological investigations will allow staging of the disease and specific
      localisation for biopsies.

PMID- 20681369
TI  - Wyburn-Mason syndrome: a case report.
AB  - OBJECTIVE: Wyburn-Mason syndrome is a rare disease associated with multiple
      arteriovenous malformations of the brain, orbit, and face resulting from an
      insult occurring during embryonic development. CASE REPORT: We present the
      clinical and radiological features of a 47-year-old-man with Wyburn-Mason
      syndrome who suffered from recurrent bleeding episodes primarily at the nasal
      corner of the left orbit. After radiotherapy and several angioembolisations,
      surgical reduction with exenteration of the left orbit was performed and resulted
      in reduced bleeding. Two years later the patient presented with maxillary sinus
      empyema. Due to massive endonasal bleeding, endoscopy could not be performed and
      the maxillary empyema was treated via a transorbital approach. CONCLUSION:
      Although close observation represents the standard of care in Wyburn-Mason
      syndrome, patient-specific management decisions are required in the presence of
      symptoms or complications. In the presented case, surgical intervention proved to
      be successful.

PMID- 20681370
TI  - Uncommon presentation of nasopharyngeal extramedullary plasmacytoma: a case
      report and literature review.
AB  - OBJECTIVE: We report an exceptional presentation of extramedullary plasmacytoma
      of the nasopharynx without bone marrow involvement or other characteristics of
      multiple myeloma. METHOD: Case report and a review of the world literature
      concerning the clinical presentation, histopathological features, optimal
      treatment and prognosis of nasopharyngeal extramedullary plasmacytoma. RESULTS:
      Reports of patients with symptomatic extramedullary plasmacytomas of the
      nasopharynx eventually being documented with histopathological evidence are not
      uncommon; however, the converse appears to be an extremely rare event. The
      patient was completely asymptomatic and following a paroxysm of coughing,
      expectorated a polypoidal nodule, which on histopathological investigation had
      features suggestive of extramedullary plasmacytoma. CONCLUSION: Although these
      tumours commonly present with significant nasal symptoms, this exceptional
      presentation in an asymptomatic patient has never been previously reported.
      Unusual presentations of rare tumours can pose considerable diagnostic dilemmas
      to both the surgeon and histopathologist. Awareness of these rarities is
      important to ensure the best patient care.

PMID- 20681371
TI  - A neuroendocrine tumour of the sphenoid sinus and nasopharynx: a case report.
AB  - It is rare for neuroendocrine tumours to originate in the sphenoid sinus and the
      nasopharynx. Neuroendocrine tumours can be classified into typical carcinoids,
      atypical carcinoids and small cell neuroendocrine carcinomas. Here we report the
      case of a 48-year-old man with a typical carcinoid tumour of the nasopharynx and
      sphenoid sinus. This is a very rare diagnosis, and only a few cases of a typical
      carcinoid in this region have been described in the literature.

PMID- 20681372
TI  - A historical vignette (18). The King's Evil: scrofula, physicians and the Royal
      Touch.
AB  - The King's evil, or scrofula, were the terms used in the past to designate what
      we now call tuberculous adenitis of the neck. Royalty, including the kings of
      France, possessed the gift of curing this malady by "Royal Touch". What was the
      attitude of the physicians towards this miraculous power? There was at least
      official collusion between the physician and the magical powers of the sovereign.
      Both sides were well advised to show consideration for one another (Figure 1).

PMID- 20681373
TI  - The EVAR Trial 1: has it led to a change in practice?
AB  - OBJECTIVES: To assess whether the publication of the EVAR Trial 1 (June 2005) had
      an impact on practice in our centre. METHODS: A retrospective study of all
      patients undergoing abdominal aortic aneurysm (AAA) repair in Leicester, from the
      year before publication of EVAR Trial 1 data to the year after (July 2004 - June
      2006). Data from the study period was then compared with practice over the last
      six years (January 2000 - December 2006). RESULTS: The proportion of endovascular
      aneurysm repairs (EVARs) did not change significantly in the year following
      publication of EVAR Trial 1 data (52% VS 57%, p=0.64). The mean age of patients
      offered open repair (OR) fell in the year following publication (69 years +/-
      6.68 vs 72 years +/- 5.71, p<0.05). Despite this, there was no significant change
      in their fitness (physiological POSSUM scores: 19.2 +/- 3.91 vs 18.2 +/- 3.74,
      P=0.30). There was an overall increase in the percentage of EVARs in the years
      2000 (28%) to 2006 (57%). CONCLUSION: There was no significant difference in the
      percentage of EVARs between the two years of study. However, over the last six
      years, there has been an increasing number performed in our unit and we now do
      more EVARs than ORs.

PMID- 20681374
TI  - An observational cohort study of the management and outcomes of vascular trauma.
AB  - OBJECTIVES: To evaluate aetiology, presentation, management and mortality
      following iatrogenic and non-iatrogenic vascular trauma in a regional vascular
      centre. METHODS: Retrospective observational cohort study of patients presenting
      with vascular trauma during a seven year period between January 2000 and December
      2006. RESULTS: 182 cases of vascular trauma were identified (averaging 26 cases
      p.a.). The majority (n=132, 73%) were iatrogenic and tended to occur in patients
      aged >45 years, while 50 (27%) were penetrating/blunt, non-iatrogenic and
      predominantly occurred in younger males. The majority of iatrogenic vascular
      injuries (80/132) (61%) followed a cardiac intervention (angiography n=56,
      angioplasty n=23, pacemaker insertion n=1) and are now increasingly treated by
      non-operative therapies (thrombin, coils and covered stents). Overall, non
      iatrogenic vascular trauma was associated with 4% mortality, compared with 7%
      following iatrogenic injury. However, while iatrogenic trauma of cardiological
      origin was associated with a mortality of only 1.3% (1/80), iatrogenic trauma of
      non-cardiological origin incurred a mortality of 17% (9/52). CONCLUSIONS: The
      commonest cause of vascular trauma (and with the lowest mortality rate) was
      cardiological related iatrogenic injury. However, while non-cardiological
      iatrogenic injury occurred with the same incidence as penetrating/blunt trauma,
      it was associated with a fourfold excess mortality.

PMID- 20681375
TI  - A definitive role for sentinel lymph node mapping with biopsy for cutaneous
      melanoma of the head and neck.
AB  - AIMS: The aim of this study was to evaluate the role, if any, of sentinel lymph
      node mapping (SLNM) with biopsy (SLNB) in patients with cutaneous melanoma of the
      head and neck. METHODS: Consecutive patients with cutaneous melanoma of the head
      and neck regions undergoing SLNM with biopsy were identified from a departmental
      database comprising 480 patients in total from 2000-2007. Factors examined
      included demographic data, histological subtype, site and depth of lesion, pre
      operative lymphoscintigraphy, percentage of positive SLNs, regional recurrence in
      the setting of a negative SLNB result (false-negative rate), complications,
      further lymphadenectomy, percentage of skin grafting required and follow-up.
      RESULTS: The median patient age was 51 years (range 18-90 years). The mean
      Breslow depth was 3.25 mm (range 1-19 mm). Five patients presented with stage
      III/IV disease. A SLN was identified in 27/40 patients who underwent head and
      neck SLN mapping (mean two lymph nodes per patient). Of these, six (22%) patients
      were positive for metastatic melanoma. The false-negative rate was 9.5%. The
      median follow up for patients was 39.6 months (range 12-96 months). No facial
      nerve injury or other major morbidity occurred. CONCLUSIONS: This study indicates
      that SLNB is a reliable and safe technique to diagnose regional spread from head
      and neck cutaneous melanoma. It is more difficult than at other sites. These
      lesions have a higher incidence of failed SLN mapping and a higher rate of
      recurrence following negative SLNB, when compared to truncal and extremity
      lesions. Nodular melanomas are more likely to fail the sentinel lymph node
      mapping procedure than other histological subtypes.

PMID- 20681376
TI  - What is in a name--patients' view of the involvement of 'care practitioners' in
      their operations.
AB  - BACKGROUND: There has been a plethora of new job titles emerging in the NHS.
      While the term 'nurse practitioner' was fairly well received, and offers a pretty
      clear indication of the background of the person working, other new titles can be
      misleading. Since 2003, when the NHS Modernisation Agency proposed its 'Changing
      Workforce Programme', nurses and other allied health professionals were recruited
      and trained to perform 'simple operations'. The surgical care practitioner is
      being developed along with other practitioners. OBJECTIVE: To find out whether
      patients are able to identify healthcare professionals by their title and what do
      patients think about a non-medically qualified person carrying out their
      operations. METHODS: A cross-sectional survey of ENT patients using a
      questionnaire. MAIN FINDINGS: Titles similar to those of medically qualified
      professionals--anaesthetic practitioner, consultant nurse and surgical care
      practitioners--can lead patients to think that they are doctors. Fifty-three per
      cent of the respondents agreed that not all hospital visits need to be attended
      by a doctor, but if an operation is needed, 92% of respondents thought it should
      be carried out by someone who is medically trained. Ninety-four per cent stated
      that they should be informed if this is not the case. Seventy-nine per cent of
      the respondents stated that they would rather wait longer to be operated on by a
      doctor than being operated on earlier by someone who is not medically qualified
      but trained to perform the operation only. This result is significant, p<0.001).
      CONCLUSION: Patients do find the different titles confusing, with many preferring
      a more transparent approach in knowing who their surgeon is. The majority would
      prefer to wait longer for their operation if this means it is carried out by a
      doctor.

PMID- 20681377
TI  - Primary peritonectomy/HIPEC for disseminated peritoneal adenomucinosis achieves
      much lower recurrence rates and better survival than secondary procedures.
AB  - BACKGROUND: Two main treatment options are available for pseudomyxoma peritonei
      (PMP) and disseminated peritoneal adenomucinosis (DPAM)--incomplete cytoreductive
      (debulking) surgery and peritonectomy with intraperitoneal chemotherapy. Several
      studies have demonstrated improved survival with peritonectomy. This study
      analyses outcome following peritonectomy in patients undergoing a primary
      procedure compared to those who have had previous debulks. METHODS: Between April
      1997 and May 2008, 63 patients underwent peritonectomy for DPAM--38 had had
      previous debulk(s) and 25 underwent primary peritonectomy. Patients were followed
      up at three- to six-monthly intervals postoperatively, with a mean follow-up time
      of 21 and 34 months, respectively. RESULTS: Mean survival for patients undergoing
      primary peritonectomy was 109.8 months. Mean survival for patients with previous
      debulks was 49.2 months (p=0.027). Five-year survival was 95.5% in the primary
      peritonectomy group and 67.5% in the previous debulk group. CONCLUSION: Disease
      recurrence after primary peritonectomy for DPAM is significantly less frequent
      than after secondary peritonectomy.

PMID- 20681378
TI  - Deprivation influences the functional outcome from total hip arthroplasty.
AB  - Socioeconomic inequality through deprivation and access to healthcare is an
      aetiological factor in many disease processes. It is associated with the
      development of osteoarthritis, the need for joint arthroplasty and poorer access
      to secondary healthcare. Few studies have investigated the influence of
      deprivation on the function of patients undergoing total hip arthroplasty. The
      aim of this study was to investigate the association between deprivation and
      function in these patients before their operation and at 18 months. The secondary
      aim was to investigate if deprivation was associated with comorbidity or adverse
      outcomes. A prospectively database of functional scores of 1865 patients
      undergoing total hip arthroplasty over seven years was used. Deprivation was
      categorized using the Scottish Index of Multiple Deprivation (SIMD) government
      rating. The most deprived quintiles had lower absolute functional scores at time
      of operation. At 18 months the least deprived quintile had a greater SF36
      physical function score and relative improvement. Deprivation was not linked with
      length of stay or BMI. There was a higher proportion of ASA (American Society of
      Anesthesiologists) category 1 patients in the least deprived group signifying
      less comorbidity. Smoking was more prevalent in patients from areas of greater
      deprivation. There was no observed difference in mortality, infection,
      dislocation or thromboembolism. This study demonstrates a socioeconomic gradient
      in the function of patients undergoing total hip arthroplasty. Further
      investigation is required to elucidate the biological and social mechanisms
      driving these outcomes, and to determine whether these gradients persist at
      longer term follow-up. LEVEL OF EVIDENCE: II (Prognostic Studies--Investigating
      the effect of a patient characteristic on the outcome of disease).

PMID- 20681379
TI  - Aspirations and solutions--a 20 year journey through dental local anaesthetics.
AB  - This paper describes clinical and laboratory investigations concerned with the
      delivery, comfort, systemic effects and efficacy of dental local anaesthesia.
      Factors influencing the aspirating ability of dental local anaesthetic delivery
      systems are discussed. The effects of adrenaline in dental local anaesthetic
      solutions on plasma potassium levels and on the transplanted heart are described.
      The use of an infiltration technique as an alternative to the inferior alveolar
      nerve block in the mandible is discussed.

PMID- 20681380
TI  - Total knee arthroplasty in patients with peripheral vascular disease.
AB  - Vascular complications following total knee arthroplasty (TKA) are rare in the
      general population; however, the consequence could be devastating and limb
      threatening. Many of the patients who develop these complications, if not all,
      have pre-existing peripheral vascular disease (PVD). Following guidelines in the
      pre-operative assessment, intra-operative procedure and post-operative management
      in this group of patients can help orthopaedic surgeons to assess candidates for
      TKA and trim down the arterial complications afterwards. OBJECTIVE: To propose a
      strategy to assess TKA candidates with underlying PVD, in order to address the
      increasing concerns of the orthopaedic surgeons with regard to the likelihood of
      vascular complications in these patients. METHODS: Review of the literature
      looking for relevant studies and case reports using different medical search
      engines (PubMed, EMbase and Cochrane Library). RESULTS: Our search produced very
      few studies relevant to our topic. Most of these are case reports dealing with
      various vascular complications following TKA and are therefore not helpful in
      making conclusive recommendations. However, there are a handful of studies that
      have specifically addressed this issue and have been included in our review.
      CONCLUSION: Vascular complications following TKA are rare (<0.5%). There are
      conflicting views in the literature with regard to the optimum management of
      these patients. However, patients with risk factors of PVD should be referred to
      the local vascular surgeons for assessment prior to TKA. The use of tourniquet in
      these patients is generally not recommended and should be based on the advice
      obtained from vascular surgeons. Individual orthopaedic surgeons or units,
      together with their vascular colleagues, should have agreed protocols for pre-
      and post-operative vascular assessments of patients undergoing TKA.

PMID- 20681381
TI  - Molecular pathology--the future?
AB  - The diagnosis and management of complex disease requires multidisciplinary
      clinical collaboration. Histopathological assessment of tissues is an important
      part of this approach and relies on the morphological appraisal of stained
      tissues by light microscopy. Although considered the 'gold standard', morphology
      alone is becoming increasingly insufficient in disease where molecular
      characterisation has altered clinical practice. As the ability to define the
      molecular alterations associated with disease expands, the requirement to analyse
      such alterations for diagnostic and therapeutic purposes follows suit. Despite
      the widespread use of small scale molecular approaches such as
      immunohistochemistry and fluorescent in situ hybridisation, the demand for
      detailed molecular classification of disease states increases unabated. In this
      review, we summarise the clinical applications of various molecular techniques
      already used within the modern histopathology department. Thereafter, we consider
      novel high throughput, array based technologies and their possible impact on
      future histopathological practice.

PMID- 20681382
TI  - Simple technique for exsanguination of the hand.
AB  - Hand surgery is facilitated by the production of a bloodless operative field by
      exsanguination and the use of a pneumatic tourniquet. Exsanguination can be
      achieved by a variety of techniques, including elevation alone, use of an Esmarch
      or crepe bandage, or a Rhys-Davies exsanguinator. We present a simple, effective
      method of exsanguination of the hand for use in procedures performed under local
      anaesthesia such as carpal tunnel decompression. No additional equipment is
      required and therefore there is no risk of transmission of infection. The hand is
      exsanguinated after surgical preparation and draping, thus minimising the
      tourniquet time.

PMID- 20681383
TI  - Re: Perianal surgery in patients prescribed nicorandil may be hazardous.

PMID- 20681384
TI  - Re: Diathermy training and usage trends among surgical trainees--will we get our
      fingers burnt? Assiotis A, Christofi T, Raptis DA et al. Surgeon 2009; 7 (3): 132
      36.

PMID- 20681385
TI  - Re: Derham C, Vohra RS, Homer-Vanniasinkam S. Academia and MMC: uncomfortable bed
      fellows? Surgeon 2009; 7(7): 4-5.

PMID- 20681386
TI  - I'm a nurse, but call me doctor!

PMID- 20681387
TI  - The Rehabilitation Nursing Foundation celebrates 20+ years of funded research.
AB  - The history and trajectory of the Rehabilitation Nursing Foundation (RNF), the
      research arm of the Association of Rehabilitation Nurses, is presented in this
      article. From 1988 through 2008, 52 RNF research grants have been awarded to 49
      researchers. Since 1995, this research award program has been guided by the
      Rehabilitation Nursing Research Agenda. Funded studies have varied in focus from
      pediatrics to geriatrics, to specific chronic conditions, and to administrative
      and management issues, providing a basis for the development of rehabilitation
      nursing science. Strategies for successful RNF grant writing are also included in
      this article.

PMID- 20681388
TI  - A time series analysis of falls and injury in the inpatient rehabilitation
      setting.
AB  - The purpose of this study is to assess whether falls and injuries are influenced
      by a temporal pattern (defined as a pattern based on the time of day) in the
      inpatient acute rehabilitation unit/hospital (IRU/H) setting. A retrospective
      chart review and analysis of falls and injuries among inpatients admitted to our
      facility during a 9-month period was performed. The sample consisted of 367
      patients who had fallen at least once; 71 had repeated falls, bringing the total
      number of falls to 438. Significant variation in the prevalence of falls (chi2 =
      24.1, p <. 01) and injuries (chi2 = 12.90, p < .01) based on time of day and
      shift was observed. In addition, a temporal pattern of fall-related injuries with
      patients who had sustained stroke and brain injury (chi2 = 12.74, p = .045) was
      also observed. The findings from this study allow for the development of
      interventions that are appropriate when falls and injury are most prevalent for
      different clinical populations in the IRU/H setting.

PMID- 20681389
TI  - Poststroke shoulder pain: inevitable or preventable?
AB  - Cerebral vascular accident or stroke is recognized as the leading cause of
      disability in the United States; consequently, it is important that all
      healthcare professionals working with this population develop competency of care
      to promote functional recovery. One of the most profound effects of stroke is
      upper-extremity dysfunction. With correct handling, proper positioning, and
      ongoing patient-caregiver education, healthcare professionals can positively
      influence upper-extremity recovery and prevention of poststroke shoulder pain. In
      doing so, they will help patients avoid the mass effect that pain can impart on
      daily routines. The purposes of this article are to describe poststroke shoulder
      pain, discuss possible causes of shoulder pain, and detail best practices nurses
      can use to prevent or minimize poststroke shoulder pain.

PMID- 20681390
TI  - Rethinking intervention strategies in stroke family caregiving.
AB  - Stroke is a condition that affects both patients and family members who provide
      care and support. Because stroke is an unexpected traumatic event that suddenly
      forces family members into a caregiving role, caregivers often experience an
      overwhelming sense of burden, depression, and isolation; a decline in physical
      and mental health; and reduced quality of life. Caregiver health is inextricably
      linked to a stroke survivor's physical, cognitive, and psychological recovery.
      Evidence suggests that informational interventions alone are not as effective in
      meeting the complex needs of stroke caregivers as interventions that combine
      information with other support services. This article discusses issues related to
      stroke caregiving and proposes comprehensive strategies designed to meet the
      poststroke recovery needs of both patients and caregivers. Suggested strategies
      include a comprehensive assessment specific to caregiver needs, skills, and
      resources and case management services designed to provide continuity of care
      across the stroke-recovery trajectory.

PMID- 20681391
TI  - Consensus-validation study identifies relevant nursing diagnoses, nursing
      interventions, and health outcomes for people with traumatic brain injuries.
AB  - A consensus-validation study used action research methods to identify relevant
      nursing diagnoses, nursing interventions, and patient outcomes for a population
      of adults with traumatic brain injury (TBI) in long-term care. In meetings
      totaling 159 hours to reach 100% consensus through group discussions, the three
      classifications of NANDA International's (NANDA-I's) approved nursing diagnoses,
      the Nursing Interventions Classification (NIC), and the Nursing Outcomes
      Classification (NOC) were used as the basis for three nurses experienced in
      working with adults with TBI to select the elements of nursing care. Among almost
      200 NANDA-I nursing diagnoses, 29 were identified as relevant for comprehensive
      nursing care of this population. Each nursing diagnosis was associated with 3-11
      of the more than 500 NIC interventions and 1-13 of more than 300 NOC outcomes.
      The nurses became aware of the complexity and the need for critical thinking. The
      findings were used to refine the facility's nursing standards of care, which were
      to be combined with the interdisciplinary plan of care and included in future
      electronic health records.

PMID- 20681395
TI  - Ward sisters need more power, leadership summit told.

PMID- 20681396
TI  - Call for restoration of laundry facilities to prevent contamination of uniforms.

PMID- 20681392
TI  - Psychological resilience and depressive symptoms in older adults diagnosed with
      post-polio syndrome.
AB  - Depression is a serious comorbidity in people with disabilities; however, few
      studies have focused on depressive symptoms in older adults with post-polio
      syndrome (PPS). This study used a resilience conceptual framework that focused on
      patient psychosocial strengths to investigate the relationship between
      psychological resilience factors (e.g., acceptance, self-efficacy, personal
      resources, interpersonal relationships, self-rated health, spiritual growth,
      stress management) and depressive symptoms in a large sample (N = 630) of people
      older than 65 years who were diagnosed with PPS. Forty percent of the sample
      scored > or = 10 on the Center for Epidemiologic Studies Short Depression Scale
      (CES-D10), which is a higher percentage than what has been previously cited in
      other studies; however, 53% of the sample had good or excellent self-rated
      health, suggesting psychological resilience. Depression scores were regressed on
      seven selected resilience factors after controlling for functional limitations.
      Four of the seven variables accounted for 30% of the variance in depressive
      symptoms, with spiritual growth representing the main predictor (beta = -.26).
      The implications for rehabilitation nurses in developing a patient-strengths
      perspective in the assessment and counseling of older adults with PPS are
      discussed.

PMID- 20681398
TI  - Be socially savvy.

PMID- 20681399
TI  - How senior nurses can make change happen.
AB  - The Health Foundation Leaders for Change scheme, which ended last year, was a
      structured learning programme designed to equip healthcare professionals with the
      skills and knowledge needed to lead sustainable projects to improve local
      services. In this article, two of the participants of the last cohort, consultant
      nurse in perioperative care at University Hospitals Bristol NHS Foundation Trust
      Clare Evans and divisional senior nurse at the University Hospitals of Morecambe
      Bay NHS Trust Lynne Wyre, share their experiences.

PMID- 20681400
TI  - High impact actions: preventing falls and encouraging exercise.
AB  - This article, the second in a series on the NHS Institute for Innovation and
      Improvement's eight high impact actions, reviews the roles played by nurses and
      local organisations in preventing falls among older people through early
      intervention and the promotion of active lifestyles.

PMID- 20681401
TI  - Human rights-based care for older people.
AB  - Care for older people is often presented in the media as unfair and
      disrespectful, wherein older people do not receive equality of autonomy, dignity
      and treatment. This article examines how nurse managers can reflect on these, and
      their own, perceptions of care for older people to influence service provision in
      their departments or organisations.

PMID- 20681402
TI  - Six simple steps to ensure you achieve your aims.
AB  - Goal setting is a common method for managers and leaders to set the direction of
      activities. Without clear goals, activities can continue for too long or never
      reach fruition. This article presents two simple templates for easy and
      straightforward goal setting that can involve health or other issues, and can be
      used at work or home.

PMID- 20681403
TI  - Clinical audit: shining a light on good practice.
AB  - Healthcare organisations undertake quality assurance to produce safe and
      effective patient care systems. Statutory quality assurance requirements are met
      through external reviews, monitoring and inspection processes, and each NHS trust
      must produce a corporate annual quality account. However, this can result in
      approaching audits as if they are 'tick-box activities'. This article discusses
      how organisations can avoid this trap by applying audit results to practice.

PMID- 20681404
TI  - Establishing a sustainable nursing workforce.
AB  - Occupational sustainability in healthcare services involves meeting the demands
      of a changing NHS without compromising the health and wellbeing of nurses. This
      article examines occupational sustainability in the nursing profession, focusing
      on issues of nursing workload, employee health and recruitment issues, and
      workforce diversity.

PMID- 20681405
TI  - Anticancer effect of a novel 2-arylidene-4,7-dimethyl indan-1-one against human
      breast adenocarcinoma cell line by G2/M cell cycle arrest.
AB  - A novel compound 2-arylidene-4,7-dimethyl indan-1-one synthesized was screened
      for anticancer effect against the human breast adenocarcinoma cell line, MCF-7.
      An IC50 value of > or = 80 microM, nontoxic to the normal breast cell line HBL
      100, showed complete inhibition of the MCF-7 cells. Analysis of mechanisms showed
      nuclear fragmentation and DNA laddering in gel electrophoresis. GSH and GR levels
      were found to be reduced after the compound treatment. Cell cycle analysis using
      fluorescent cytometry revealed G2/M phase arrest, which indicates the compound
      deserves consideration for further studies against cancer.

PMID- 20681406
TI  - The inhibitor of growth 1 (ING1) is involved in trichostatin A-induced apoptosis
      and caspase 3 signaling in p53-deficient glioblastoma cells.
AB  - Prognosis for patients with glioblastoma multiforme (GBM) is poor. Inhibitors of
      histone deacetylases (HDACi) like trichostatin A (TSA) are promising alternatives
      to conventional treatment. Deficient tumor suppressor functions, such as TP53
      mutations and p14(ARF)/p16(INK4a) deletions, are characteristic for GBM and can
      cause resistance to DNA damaging agents such as cisplatin and to HDACi like TSA.
      The type II tumor suppressor Inhibitor of growth 1 (ING1) is involved in DNA
      damage response and histone modification. We have previously shown that ING1 is
      downregulated in GBM and involved in glioma-induced angiogenesis and in cisplatin
      induced apoptosis in malignant glioma cells. Hence, the goal of our present study
      was to investigate whether TSA affects ING1 protein expression and also whether
      modulating ING1 levels affects TSA-induced apoptosis in malignant glioma cells
      that contain deficient p53 function and inactive pl4(ARF)/p16(INK4a) signaling.
      If so, we asked, which apoptotic pathway might be the major mediator beyond this
      interaction. To test whether ING1 proteins function in TSA-induced apoptosis in
      GBM, we analyzed TSA effects in LN229 GBM cells, which harbor TP53 mutations and
      INK4a deletion, following ING1 knockdown by siRNA. Expression of ING1, acetylated
      core histones H3 and H4, and the proapoptotic proteins caspase 3 and Fas
      associated death domain (FADD) was determined by Western blotting. Percentages of
      apoptotic cells were obtained by flow cytometry. TSA induced the major ING1
      isoform p33(ING1b) and increased levels of both histone acetylation and apoptosis
      in LN229 cells. ING1 knockdown cells revealed marked resistance to TSA-induced
      apoptosis, impairment of caspase 3 activation, and suppression of FADD. The data
      suggest that ING1 contributes to TSA-induced apoptosis in GBM cells with
      deficient p53 and p14(ARF)/p16(INK4a) functions, possibly by regulating
      FADD/caspase 3 signaling.

PMID- 20681407
TI  - Intrinsic mitochondrial membrane potential change and associated events mediate
      apoptosis in chemopreventive effect of diclofenac in colon cancer.
AB  - The present study explored the role of intrinsic mitochondrial membrane potential
      (delta psi M) in NSAID-induced apoptosis in the early stages of colon cancer. 1,2
      Dimethylhydrazine dihydrochloride (DMH) was used to induce colon cancer and its
      chemoprevention was studied by diclofenac in a rat model. After 6 weeks of
      treatment with DMH (early stage), morphological analysis revealed a marked
      occurrence of preneoplastic features [i.e., mucosal plaque lesions (MPLs) in the
      colonic tissue]. Coadministration of diclofenac with DMH resulted in a
      significant reduction of these lesions, thereby proving the chemopreventive
      efficacy of diclofenac at the chosen anti-inflammatory dose. DMH treatment also
      led to a significant increase in delta psi M in the isolated colonocytes as
      assessed by JC-1 fluorescent staining, measured both by fluorescence microscopy
      and spectrofluorometerically. Further, there was seen a reduction in the number
      of cells showing low delta psi M, and hence monomer intensity of JC-1 by DMH
      treatment. To study the mechanism of these alterations in delta psi M in the
      present work, we studied the protein expression of important proapoptotic
      proteins, cytochrome c and Bax, by Western blot analysis and
      immunohistochemistry. DMH treatment reduced the mitochondrial translocation of
      Bax whereas cytochrome c was found to be located prominently in the mitochondria.
      Protein expression of antiapoptotic Bcl-2 was also studied in the colonic mucosa,
      which was expectedly found to be overexpressed after DMH treatment. Diclofenac
      treatment ameliorated the elevated delta psi M and its associated events to exert
      its chemopreventive action against early stages of colon cancer.

PMID- 20681409
TI  - Accelerated partial breast irradiation: Use of four-dimensional CT for target
      localization and assessment of intrafractional motion.
AB  - The aim of this study was to use four-dimensional CT (4DCT) in the planning of 3D
      conformational external beam radiation therapy (3DCRT) for patients with early
      stage breast cancer. A total of nine Chinese women who received breast
      conservation treatment were included in this study. Target localization and
      movement (range of motion) during normal respiration were assessed using
      ultrasound and 4DCT. Plans based on 3DCT and 4DCT scans were developed in
      accordance to RTOG0319 guidelines and dose delivery comparisons were made between
      these plans. The mean ranges of motion of the excision cavity volume as
      determined using 4DCT were 1.03 +/- 0.51, 2.08 +/- 0.92, and 1.27 +/- 0.58 mm in
      the right-left, anterior-posterior, and superior-interior directions,
      respectively. There were no significant differences between the mean and maximum
      PTV-E doses or the volume receiving 95% of the prescribed dose (V95). 4D plan
      prescribed dose levels were significantly lower (p < 0.05) than 3D plan levels
      for all of the following: ipsilateral breast V100, ipsilateral lung V30, and
      contralateral lung V5. Maximum contralateral breast and thyroid doses were also
      significantly lower with the 4D plan (p < 0.05). This study highlights the
      usefulness of 4DCT for the planning of 3DCRT in breast cancer patients. Our
      findings suggest that the use of 4DCT can lead to improvements in target
      definition and decreases in normal tissues irradiation.

PMID- 20681408
TI  - Zoledronate stimulates gamma delta T cells in prostate cancer patients.
AB  - Androgen deprivation therapy is the mainstay of treatment for prostate cancer.
      Given its frequent failure, new therapy that reduces prostate cancer progression
      would be a breakthrough in treating this disease. Bisphosphonates are well
      established agents for treating skeletal-related events (SREs) in prostate cancer
      patients with bone metastases. Exposure to bisphosphonates may not only reduce
      the incidence of SREs, but also have anticancer effects by modulating a patient's
      immunity. The purpose of this study was to examine the effect of zoledronate
      (ZOL) on gamma delta T cells, serum prostate-specific antigen (PSA) levels, and
      velocities. The effect of ZOL, with and without IL-2, on gamma delta T cell
      activation was examined in vitro. Furthermore, the activated state and the number
      of gamma delta T cells and changes in serum PSA levels were examined for patients
      who received ZOL infusion for the prevention of SREs. We found that ZOL activated
      gamma delta T cells, and the number of gamma delta T cell was increased when IL-2
      was administered with ZOL in vitro. Comparisons before and after the first ZOL
      infusion revealed that gamma delta T cells in peripheral blood were activated by
      ZOL. Moreover, after the first ZOL treatment, reduction in serum PSA was observed
      in 3 of 11 patients, and reduction in PSA velocity was observed in 5 of 10
      patients. Our findings indicate that ZOL stimulates gamma delta T cells in vivo
      and in vitro. This study provides further insight into the ability of gamma delta
      T cells to induce an antitumor immune response.

PMID- 20681410
TI  - Allelic loss of the ING gene family loci is a frequent event in ameloblastoma.
AB  - Ameloblastoma is the most frequently encountered odontogenic tumor, characterized
      by a locally invasive behavior, frequent recurrences, and, although rare,
      metastatic capacity. Loss or inactivation of tumor suppressor genes (TSGs) allows
      cells to acquire neoplastic growth. The ING family proteins are tumor suppressors
      that physically and functionally interact with p53 to perform important roles in
      apoptosis, DNA repair, cell cycle regulation, and senescence. TP53 genetic
      alterations were reported to infrequently occur in ameloblastoma. Considering
      that other TSGs related to TP53 could be altered in this tumor, we focused our
      study on the ING family genes. We analyzed the loss of heterozygosity (LOH)
      status of the ING family (ING1-ING5) chromosomal loci in a group of
      ameloblastomas by microsatellite analysis, and correlated the ING LOH status with
      clinicopathological characteristics. By using specific microsatellite markers,
      high frequency of LOH was found at the loci of each ING gene family member (33.3
      72.2%). A significant relationship was shown between LOH of D2S 140 (ING5 locus)
      and solid tumor type (p = 0.02). LOH of ING3MS (ING3 locus) was also high in
      solid type tumors, showing a near significant association. In addition, a notable
      tendency toward higher LOH for half of the markers was observed in recurrent
      cases. LOH of ING family genes appears as a common genetic alteration in solid
      ameloblastoma. The current study provides interesting novel information regarding
      the potential prognostic significance of the allelic loss of the ING gene family
      loci in ameloblastoma tumorigenesis.

PMID- 20681411
TI  - Missing pieces. Healthcare waits on regulations that will fill in the ARRA
      puzzle.

PMID- 20681412
TI  - Achieving coding consistency.
AB  - Even small departments may never experience complete harmony in their assignment
      of codes, but they have good motivation for achieving as much consistency as they
      can. Training, communication, monitoring, and coding reviews help reach that
      goal, HIM experts say.

PMID- 20681413
TI  - Lean coding machine. Facilities target productivity and job satisfaction with
      coding automation.
AB  - Facilities are turning to coding automation to help manage the volume of
      electronic documentation, streamlining workflow, boosting productivity, and
      increasing job satisfaction. As EHR adoption increases, computer-assisted coding
      may become a necessity, not an option.

PMID- 20681414
TI  - Ready, set, automate. Preparing for automation in coding workflows.

PMID- 20681415
TI  - Smart training on privacy and security.

PMID- 20681416
TI  - Managing patient-provided information in EHRs.

PMID- 20681417
TI  - A primer on MDS 3.0. An overview of MDS 3.0 for the October 1 transition.

PMID- 20681418
TI  - E-discovery from the judicial perspective.

PMID- 20681420
TI  - Sweeping revisions for cancer registries. Like coders, cancer registrars adapting
      to major changes.

PMID- 20681419
TI  - Automated coding workflow and CAC practice guidance.

PMID- 20681421
TI  - Establishing a CDI program. How one organization leveraged nursing and coding
      skills to improve clinical data.

PMID- 20681423
TI  - ICD-when? Nearly half of organizations yet to begin ICD-10 preparations.

PMID- 20681422
TI  - Transitioning to CAC. The skills and tools required to work with computer
      assisted coding.

PMID- 20681424
TI  - Environmental and human health risks of aerosolized silver nanoparticles.
AB  - Silver nanoparticles (AgNPs) are gaining attention from the academic and
      regulatory communities, not only because of their antimicrobial effects and
      subsequent product applications, but also because of their potential health and
      environmental risks. Whereas AgNPs in the aqueous phase are under intensive
      study, those in the atmosphere have been largely overlooked, although it is well
      established that inhalation of nanoparticles is associated with adverse health
      effects. This review summarizes the present state of knowledge concerning
      airborne AgNPs to shed light on the possible environmental exposure scenarios
      that may accompany the production and popularization of silver nanotechnology
      consumer products. The current understanding of the toxicity of AgNPs points
      toward a potential threat via the inhalation exposure route. Nanoparticle size,
      chemical composition, crystal structure, surface area, and the rate of silver ion
      release are expected to be important variables in determining toxicity. Possible
      routes of aerosolization of AgNPs from the production, use, and disposal of
      existing consumer products are presented. It is estimated that approximately 14%
      of silver nanotechnology products that have been inventoried could potentially
      release silver particles into the air during use, whether through spraying, dry
      powder dispersion, or other methods. In laboratory and industrial settings, six
      methods of aerosolization have been used to produce airborne AgNPs: spray
      atomization, liquid-flame spray, thermal evaporation-condensation, chemical
      vaporization, dry powder dispersion, and manual handling. Fundamental
      uncertainties remain about the fate of AgNPs in the environment, their short- and
      long-term health effects, and the specific physical and chemical properties of
      airborne particles that are responsible for health effects. Thus, to better
      understand the risks associated with silver nanotechnology, it is vital to
      understand the conditions under which AgNPs could become airborne.

PMID- 20681425
TI  - Greenhouse gas emission mitigation relevant to changes in municipal solid waste
      management system.
AB  - Standard methods for assessing the environmental impact of waste management
      systems are needed to underpin the development and implementation of sustainable
      waste management practice. Life cycle assessment (LCA) is a tool for
      comprehensively ensuring such assessment and covers all impacts associated with
      waste management. LCA is often called "from cradle to grave" analysis. This paper
      integrates information on the greenhouse gas (GHG) implications of various
      management options for some of the most common materials in municipal solid waste
      (MSW). Different waste treatment options for MSW were studied in a system
      analysis. Different combinations of recycling (cardboard, plastics, glass,
      metals), biological treatment (composting), and incineration as well as land
      filling were studied. The index of environmental burden in the global warming
      impact category was calculated. The calculations are based on LCA methodology.
      All emissions taking place in the whole life cycle system were taken into
      account. The analysis included "own emissions," or emissions from the system at
      all stages of the life cycle, and "linked emissions," or emissions from other
      sources linked with the system in an indirect way. Avoided emissions caused by
      recycling and energy recovery were included in the analysis. Displaced emissions
      of GHGs originate from the substitution of energy or materials derived from waste
      for alternative sources. The complex analysis of the environmental impact of
      municipal waste management systems before and after application of changes in MSW
      systems according to European Union regulations is presented in this paper. The
      evaluation is made for MSW systems in Poland.

PMID- 20681426
TI  - Farm-scale evaluation of ozonation for mitigating ammonia concentrations in
      broiler houses.
AB  - This study evaluated the effectiveness of in-house ozonation within the public
      health standard limit (0.1 parts per million [ppm]) for mitigating ammonia (NH3)
      concentrations inside commercial broiler houses. The project was conducted in
      four identical tunnel-ventilated houses. Two houses served as treatment and the
      other two served as control units. The experiment was replicated in five
      consecutive flocks. Except for ozonation treatment, all other operational
      parameters including feed, broiler strain, age and number of broilers, and
      ventilation system were the same among four houses. NH3 and carbon dioxide (CO2)
      concentrations in the treatment and control houses were measured for a minimum of
      48 hr/week throughout the five flocks of 8 or 9 weeks each. The gas measurements
      were conducted using portable multigas units (PMUs). House temperatures were
      recorded with data loggers in each flock. Comparison of temperatures and CO2
      concentrations among houses indicated no significant differences in ventilation
      rates among treatment and control houses in any of the five flocks. As a result,
      comparisons of NH3 concentrations inside houses were used to evaluate the
      effectiveness of house ozonation for NH3 emission mitigation. Statistical test of
      mean NH3 concentrations for each flock separated by house indicated that the
      house-to-house variation was significantly smaller than the flock-to-flock
      variation. There was a substantial variation in NH3 concentrations across
      different flocks, but no house had consistently higher or lower mean NH3
      concentrations than any other. Evaluations for differences in mean NH3 from week
      to week, between treatment groups, and differences in week-to-week variations
      between treatment groups suggested that ozone effect was not uniform for each
      week and the effect was not statistically significant for any week. Tests of
      overall ozone treatment effect and treatment-week interaction indicated there was
      no difference in mean NH3 between the control and ozone treatment groups (P =
      0.25), nor was the week effect different for control and treatment groups (P =
      0.46). The results of this field evaluation indicate that there was no
      statistical evidence to suggest that the ozone treatment has any effect on
      average NH3 concentrations in these chicken houses.

PMID- 20681427
TI  - Uncertainty analysis of ozone formation and response to emission controls using
      higher-order sensitivities.
AB  - Understanding ozone response to its precursor emissions is crucial for effective
      air quality management practices. This nonlinear response is usually simulated
      using chemical transport models, and the modeling results are affected by
      uncertainties in emissions inputs. In this study, a high ozone episode in the
      southeastern United States is simulated using the Community Multiscale Air
      Quality (CMAQ) model. Uncertainties in ozone formation and response to emissions
      controls due to uncertainties in emission rates are quantified using the Monte
      Carlo method. Instead of propagating emissions uncertainties through the original
      CMAQ a reduced form of CMAQ is formulated using directly calculated first- and
      second-order sensitivities that capture the nonlinear ozone concentration
      emission responses. This modification greatly reduces the associated
      computational cost. Quantified uncertainties in modeled ozone concentrations and
      responses to various emissions controls are much less than the uncertainties in
      emissions inputs. Average uncertainties in modeled ozone concentrations for the
      Atlanta area are less than 10% (as measured by the inferred coefficient of
      variance [ICOV]) even when emissions uncertainties are assumed to vary between a
      factor of 1.5 and 2. Uncertainties in the ozone responses generally decrease with
      increased emission controls. Average uncertainties (ICOV) in emission-normalized
      ozone responses range from 4 to 22%, with the smaller being associated with
      controlling of the relatively certain point nitrogen oxide (NOx) emissions and
      the larger resulting from controlling of the less certain mobile NOx emissions.
      These small uncertainties provide confidence in the model applications, such as
      in performance evaluation, attainment demonstration, and control strategy
      development.

PMID- 20681428
TI  - An inexact fuzzy-chance-constrained air quality management model.
AB  - Regional air pollution is a major concern for almost every country because it not
      only directly relates to economic development, but also poses significant threats
      to environment and public health. In this study, an inexact fuzzy-chance
      constrained air quality management model (IFAMM) was developed for regional air
      quality management under uncertainty. IFAMM was formulated through integrating
      interval linear programming (ILP) within a fuzzy-chance-constrained programming
      (FCCP) framework and could deal with uncertainties expressed as not only
      possibilistic distributions but also discrete intervals in air quality management
      systems. Moreover, the constraints with fuzzy variables could be satisfied at
      different confidence levels such that various solutions with different risk and
      cost considerations could be obtained. The developed model was applied to a
      hypothetical case of regional air quality management. Six abatement technologies
      and sulfur dioxide (SO2) emission trading under uncertainty were taken into
      consideration. The results demonstrated that IFAMM could help decision-makers
      generate cost-effective air quality management patterns, gain in-depth insights
      into effects of the uncertainties, and analyze tradeoffs between system economy
      and reliability. The results also implied that the trading scheme could achieve
      lower total abatement cost than a nontrading one.

PMID- 20681429
TI  - The effect of ozone on the removal effectiveness of photocatalysis on indoor
      gaseous biogenic volatile organic compounds.
AB  - In this study, the degradation of d-limonene by photocatalytic oxidation (PCO)
      (titanium dioxide [TiO2]/ultraviolet [UV]) and by the combination of PCO and
      ozone (O3) (TiO2/UV/O3) was investigated to evaluate the enhancement effect of
      O3. The degradation of d-limonene by UV/O3 was also investigated for comparison.
      The experiments were conducted with a quartz photoreactor under various gas flow
      rates (600-1600 mL min(-1)), d-limonene concentrations (0.5-9 parts per million
      [ppm]), and relative humidity (RH) (20-80%). The d-limonene removal efficiency of
      TiO2/UV/O3, TiO2/UV, and UV/O3 ranged from 62 to 99%, from 49 to 99%, and from 46
      to 75%, respectively. The addition of 120-ppb O3 can enhance the d-limonene
      removal efficiency of PCO up to 12%. The apparent kinetic parameters (apparent
      rate constants, kapparent and Langmuir adsorption constants, Kapparent of TiO2/UV
      and TiO2/UV/O3 reactions obtained from fitting Langmuir-Hinshelwood models are
      TiO2/UV: kapparent = 1.45 x 10(-3) ppm-m sec(-1), Kapparent = 0.34 ppm(-1); TiO2/
      UV/O3: kapparent = 1.83 x 10(-3) ppm-m sec(-1), and Kapparent = 0.35 ppm(-1).
      When RH was higher than 40%, the residual intermediates yield rates of d-limonene
      of TiO2/UV/O3, TiO2/UV, and UV/O3 reactions ranged from 0.39 to 0.51 micromol
      carbon m(-2) sec(-1), 0.56 to 1.96 micromol carbon m(-2) sec(-1), and 157 to 177
      micromol carbon m(-3) sec(-1), respectively. In the photocatalytic reaction
      experiments, the addition of 120-parts per billion (ppb) O3 can reduce the
      residual intermediates yield rates of d-limonene by up to 1.46 micromol carbon m(
      2) sec(-1). These experimental results showed that O3 can enhance the
      effectiveness of photocatalysis on the removal of d-limonene.

PMID- 20681430
TI  - Gas dispersion and immobile gas volume in solid and porous particle biofilter
      materials at low air flow velocities.
AB  - Gas-phase dispersion in granular biofilter materials with a wide range of
      particle sizes was investigated using atmospheric air and nitrogen as tracer
      gases. Two types of materials were used: (1) light extended clay aggregates
      (LECA), consisting of highly porous particles, and (2) gravel, consisting of
      solid particles. LECA is a commercial material that is used for insulation, as a
      soil conditioner, and as a carrier material in biofilters for air cleaning. These
      two materials were selected to have approximately the same particle shape. Column
      gas transport experiments were conducted for both materials using different mean
      particle diameters, different particle size ranges, and different gas flow
      velocities. Measured breakthrough curves were modeled using the advection
      dispersion equation modified for mass transfer between mobile and immobile gas
      phases. The results showed that gas dispersivity increased with increasing mean
      particle diameter for LECA but was independent of mean particle diameter for
      gravel. Gas dispersivity also increased with increasing particle size range for
      both media. Dispersivities in LECA were generally higher than for gravel. The
      mobile gas content in both materials increased with increasing gas flow velocity
      but it did not show any strong dependency on mean particle diameter or particle
      size range. The relative fraction of mobile gas compared with total porosity was
      highest for gravel and lowest for LECA likely because of its high internal
      porosity.

PMID- 20681431
TI  - Evaluation of relative response factor methodology for demonstrating attainment
      of ozone in Houston, Texas.
AB  - In 2007, the U.S. Environmental Protection Agency (EPA) released guidance on
      demonstrating attainment of the federal ozone (O3) standard. This guidance
      recommended a change in the use of air quality model (AQM) predictions from an
      absolute to a relative way. This was accomplished by using a ratio, and not the
      absolute difference of AQM O3 predictions from a historical year to an attainment
      year. This ratio of O3 concentrations, labeled the relative response factor
      (RRF), is multiplied by an average of observed concentrations at every monitor.
      In this analysis, whether the methodology used to calculate RRFs is severing the
      source-receptor relationship for a given monitor was investigated. Model
      predictions were generated with a regulatory AQM system used to support the 2004
      Houston-Galveston-Brazoria State Implementation Plan. Following the procedures in
      the EPA guidance, an attainment demonstration was completed using regulatory AQM
      predictions and measurements from the Houston ground-monitoring network. Results
      show that the model predictions used for the RRF calculation were often based on
      model conditions that were geographically remote from observations and counter to
      wind flow. Many of the monitors used the same model predictions for an RRF, even
      if that O3 plume did not impact it. The RRF methodology resulted in severing the
      true source-receptor relationship for a monitor. This analysis also showed that
      model performance could influence RRF values, and values at monitoring sites
      appear to be sensitive to model bias. Results indicate an inverse linear
      correlation of RRFs with model bias at each monitor (R2 = 0.47), resulting in a
      change in future O3 design values up to 5 parts per billion (ppb). These results
      suggest that the application of RRF methodology in Houston, TX, should be changed
      from using all model predictions above 85 ppb to a method that removes any
      predictions that are not relevant to the observed source-receptor relationship.

PMID- 20681432
TI  - Combustion kinetics and emission characteristics of polycyclic aromatic
      hydrocarbons from polylactic acid combustion.
AB  - This study investigates the combustion kinetics and emission factors of 16 U.S.
      Environmental Protection Agency priority polycyclic aromatic hydrocarbons (PAHs)
      in polylactic acid (PLA) combustion. Experimentally, two reactions are involved
      in the PLA combustion process that potentially result in the release of lactide,
      acetaldehyde, and n-hexaldehyde. The products may continuously be oxidized to
      form carbon dioxide (CO2) and some PAHs produced because of incomplete
      combustion. The analytical results indicate that the emission factors for PAHs
      are in the range of not detectable to 98.04 microg/g. The emission factors are
      much lower than those of poly(ethylene terephalate) (PET) and other combustion of
      plastics. Results from this work suggest that combustion is a good choice for
      waste PLA disposal.

PMID- 20681433
TI  - The effect of emission from coal combustion in nonindustrial sources on
      deposition of sulfur and oxidized nitrogen in Poland.
AB  - Poland has one of the largest sulfur and nitrogen emissions in Europe. This is
      mainly because coal is a main fuel in industrial and nonindustrial combustion.
      The aim of this paper is to assess the amount of sulfur and nitrogen deposited
      from SNAP sector 02 (nonindustrial sources) coal combustion. To assess this
      issue, the Fine Resolution Atmospheric Multipollutant Exchange (FRAME) model was
      used. The results suggest that industrial combustion has the largest impact on
      deposition of oxidized sulfur, whereas the oxidized nitrogen national deposition
      budget is dominated by transboundary transport. The total mass of pollutants
      deposited in Poland, originating from nonindustrial coal combustion, is 45 Gg of
      sulfur and 2.5 Gg of nitrogen, which is over 18% of oxidized sulfur and nearly 2%
      of oxidized nitrogen deposited. SNAP 02 is responsible for up to 80% of dry
      deposited sulfur and 11% of nitrogen. The contribution to wet deposition is
      largest in central Poland in the case of sulfur and in some areas can exceed 11%.
      For oxidized nitrogen, nonindustrial emissions contribute less than 1% over the
      whole area of Poland. The switch from coal to gas fuel in this sector will result
      in benefits in sulfur and nitrogen deposition reduction.

PMID- 20681434
TI  - Impact of oxidation catalysts on exhaust NO2/NOx ratio from lean-burn natural gas
      engines.
AB  - Oxides of nitrogen (NOx) emitted from internal combustion engines are composed
      primarily of nitric oxide (NO) and nitrogen dioxide (NO2). Exhaust from most
      combustion sources contains NOx composed primarily of NO. There are two important
      scenarios specific to lean-burn natural gas engines in which the NO2/NOx ratio
      can be significant: (1) when the engine is operated at ultralean conditions and
      (2) when an oxidation catalyst is used. Large NO2/NOx ratios may result in
      additional uncertainty in NOx emissions measurements because the most common
      technique (chemiluminescence) was developed for low NO2/NOx ratios. In this work,
      scenarios are explored in which the NO2/NOx ratio can be large. Additionally,
      three NOx measurement approaches are compared for exhaust with various NO2/NOx
      ratios. The three measurement approaches are chemiluminescence, chemical cell,
      and Fourier-transform infrared spectroscopy. A portable analyzer with chemical
      cell technology was found to be the most accurate for measuring exhaust NOx with
      large NO2/NOx ratios.

PMID- 20681435
TI  - Effect of fractionation and pyrolysis on fuel properties of poultry litter.
AB  - Raw poultry litter has certain drawbacks for energy production such as high ash
      and moisture content, a corrosive nature, and low heating values. A combined
      solution to utilization of raw poultry litter may involve fractionation and
      pyrolysis. Fractionation divides poultry litter into a fine, nutrient-rich
      fraction and a coarse, carbon-dense fraction. Pyrolysis of the coarse fraction
      would remove the corrosive volatiles as bio-oil, leaving clean char. This paper
      presents the effect of fractionation and pyrolysis process parameters on the
      calorific value of char and on the characterization of bio-oil. Poultry litter
      samples collected from three commercial poultry farms were divided into 10
      treatments that included 2 controls (raw poultry litter and its coarse fraction
      having particle size greater than 0.85 mm) and 8 other treatments that were
      combinations of three factors: type (raw poultry litter or its coarse fraction),
      heating rate (30 or 10 degrees C/min), and pyrolysis temperature (300 or 500
      degrees C). After the screening process, the poultry litter samples were dried
      and pyrolyzed in a batch reactor under nitrogen atmosphere and char and
      condensate yields were recorded. The condensate was separated into three
      fractions on the basis of their density: heavy, medium, and light phase.
      Calorific value and proximate and nutrient analysis were performed for char,
      condensate, and feedstock. Results show that the char with the highest calorific
      value (17.39 +/- 1.37 MJ/kg) was made from the coarse fraction at 300 degrees C,
      which captured 68.71 +/- 9.37% of the feedstock energy. The char produced at 300
      degrees C had 42 +/- 11 mg/kg arsenic content but no mercury. Almost all of the
      Al, Ca, Fe, K, Mg, Na, and P remained in the char. The pyrolysis process reduced
      ammoniacal-nitrogen (NH4-N) in char by 99.14 +/- 0.47% and nitrate-nitrogen (NO3
      N) by 95.79 +/- 5.45% at 500 degrees C.

PMID- 20681436
TI  - Marine vessels as substitutes for heavy-duty trucks in Great Lakes freight
      transportation.
AB  - This paper applies a geospatial network optimization model to explore
      environmental, economic, and time-of-delivery tradeoffs associated with the
      application of marine vessels as substitutes for heavy-duty trucks operating in
      the Great Lakes region. The geospatial model integrates U.S. and Canadian
      highway, rail, and waterway networks to create an intermodal network and
      characterizes this network using temporal, economic, and environmental attributes
      (including emissions of carbon dioxide, particulate matter, carbon monoxide,
      sulfur oxides, volatile organic compounds, and nitrogen oxides). A case study
      evaluates tradeoffs associated with containerized traffic flow in the Great Lakes
      region, demonstrating how choice of freight mode affects the environmental
      performance of movement of goods. These results suggest opportunities to improve
      the environmental performance of freight transport through infrastructure
      development, technology implementation, and economic incentives.

PMID- 20681437
TI  - Managing medical bills on the brink of bankruptcy.

PMID- 20681438
TI  - Can I tell you the truth? A comparative perspective on regulating off-label
      scientific and medical information.

PMID- 20681439
TI  - Transferring behavioral interventions for global health: intellectual property
      barriers, information constraints, and possible solutions.

PMID- 20681440
TI  - [Adverse events related to bevacizumab and the management principles in non-small
      cell lung cancer].

PMID- 20681441
TI  - [Establishment and its biological characteristics of patient-derived lung cancer
      xenograft models].
AB  - BACKGROUND AND OBJECTIVE: With the ongoing need to improve therapy for lung
      cancer, there has been an increasing interest in the development of reliable
      preclinical models to test novel therapeutics. The aim of this study is to
      establish a patient-derived lung cancer xenograft model in mice and to observe
      the biological characteristics of xenografts. METHODS: Surgically resected tumor
      specimens from patients with lung cancer were implanted in the subcutaneous layer
      of the NOD/ SCID mice. Cancer specimens of percutaneous lung biopsy by CT
      fluoroscopy were implanted into the subrenal capsule of nude mouse. The
      subcutaneous carcinoma was surgically removed when it grew to approximately 1.0
      cm in diameter, and then re-transplanted into new nude mice. The growth process
      of transplanted tumor was observed. Expression of CEA, cytokeratin, and Ki67 were
      detected by immunohistochemistry. Mutations in the exons 18-21 of EGFR and exons
      12,59 of K-ras of primary and xenograft tumors were examined. The cell cycle of
      xenograft tumor cells was analyzed by flow cytometry. RESULTS: Eleven cases were
      conducted for NOD/SCID mice and nude mice modelling. The patient-derived lung
      cancer xenografts have been established successfully, and the tumor could be
      passed to new nude mice, including No 2 model (adenocasinoma), No. 3 model (small
      cell lung cancer), and No.5 model (squamous cell cancer). High homogeneity was
      found between xenograft tumors and human lung cancer in histopathology,
      immunohistochemical phenotype, and EGFR, K-ras mutation status. The S-phase
      fraction of xenograft cell cycle was prolonged, which indicated that the
      xenografts remains highly proliferated. CONCLUSION: The xenotransplantation
      models established for patient-derived lung cancer in immune deficient mice. The
      success rate is 27%. This model system displayed the biological characteristics
      of human lung cancer, suggesting that it may provide a stable, reliable, and
      useful animal model in human lung cancer research.

PMID- 20681442
TI  - [Study on the iodine 125 uptake of H460 lung cancer cell line by co-transfection
      with the human sodium/iodide symporter and the human thyroperoxidase].
AB  - BACKGROUND AND OBJECTIVE: Lung cancer harms people's health or even lives
      severely. Especially, the therapy of non-small cell lung cancer (NSCLC) has not
      been obviously improved for many years. The aim of this study is to transfer the
      human sodium/iodide symporter (hNIS) and the human thyroperoxidase (hTPO) genes
      into H460 lung cancer cell line, and to study the uptake ability of iodide after
      co-transfected hTPO and hNIS gene in cell lines. METHODS: Through cloning,
      recombination, packaging and amplifying, the recombinant adenosine virus (AdTPO)
      was constructed. Then the protein expression of AdTPO was tested by Western blot.
      After transfected hNIS gene into human lung cancer cell line H460 through
      liposome, stably expressing hNIS gene cell lines (hNIS-H460) selected by G418
      antibiotics was determined as hNIS-H460 group. Using AdTPO, hTPO gene was
      transducted into hNIS-H460, as AdTPO-hNIS-H460 group. H460 cell without hNIS gene
      was applied as control group (H460). Then, we investigated the 125I uptake assay
      of the above cells. RESULTS: We were successful in co-transfecting hNIS and hTPO
      gene into human lung cell lines H460, and were obtained hNIS and hTPO gene lung
      cancer cell lines (hNIS-H460 and AdTPO-hNIS-H460). In AdTPO-hNIS-H460, hNIS-H460
      and H460, the uptake ability of 125I was (59 637.67 +/- 1 281.13), (48 622.17 +/-
      2 242.28) and (1 440.17 +/- 372.86) counts x min(-1). The uptake ability of 125I
      was 41 fold higher in AdTPO-hNIS-H460 than in blank control H460 (P < 0.01), and
      34 fold higher in hNIS-460 than in blank control H460 (P < 0.01), and 1.2 fold
      higher in AdTPO-hNIS-H460 than in hNIS-H460 (P < 0.01). CONCLUSION: The uptake
      ability of 125I could increase by co-transfected hNIS and hTPO genes into human
      lung cancer cell lines H460.

PMID- 20681443
TI  - [Effects of recombinant human endostatin and docetaxel on MMP and its following
      anti-neoplastic effect under different administration sequences].
AB  - BACKGROUND AND OBJECTIVE: The aim of this study is to observe the changes of MMP
      2 and its regulators, and to investigate the mechanism of the two administration
      sequences of recombinant human endostatin (rh-endostatin) and docetaxel. METHODS:
      The experiment was performed as 2 stages. Firstly, nude mice with xenograft tumor
      were randomized into 2 groups as rh-endostatin-treated group with rh-endostatin
      400 microg x d(-1), d1-d14 and docetaxel-traeted group with docetaxel 10 mg x kg(
      1) x 3d(-1), d1-d14. Secondly, nude mice with xenograft tumor were randomized
      into 3 groups as concurrent administration group (rh-endostatin 400 microg x d(
      1), d1-d35, docetaxel 10 mg x kg(-1) x 3d(-1), d1-d19), endo-first group (rh
      endostatin 400 microg x d(-1), d1-d35, docetaxel 10 mg x kg(-1) x 3(d-1), d16
      d34) and model group (positive control, mice burdened tumor without treatment).
      The volume of tumor was measured during treatment. Detection of the expressions
      of MMP-2, TIMP-2, EMMPRIN and the count of microvessel density (MVD) by
      immunohistochemistry stain examination were carried out at the end of experiment.
      RESULTS: Compared with the docetaxel-treated group, more obvious down-regulation
      of expression of MMP-2, EMMPRIN (P = 0.024, P = 0.081) were observed in rh
      endostatin-treated group. No significant difference was found in TIMP-2
      expression between the 2 groups. In combined treatment groups, at the endpoint
      tumor volumes of concurrent administration group and the endo-first group were
      remarkably smaller than that in model group (P < 0.001, P = 0.003). According to
      the administration procedure, concurrent administration inhibited tumor growth
      stronger than endo-first treatment did. Both of the combined groups down
      regulated the expression of MMP-2 and decreased microvessel density (P < 0.05).
      Compared with model group, the expression of TIMP-2 was upregulated (P = 0.001)
      as well as EMMPRIN down-regulated (P = 0.018) in concurrent adminis- tration
      group. Oppositely, the same results were not observed in the endo-first group.
      CONCLUSION: The schedule of the concurrent administration group could inhibit the
      tumor growth better, and it down-regulated MMP-2 expression through TIMP-2 and
      EMMPRIN, and thus slow down the tumor growth superiorly to another schedule of
      treatment.

PMID- 20681444
TI  - [The correlation between the expression of Wnt1 and prognosis in resected non
      small cell lung cancer].
AB  - BACKGROUND AND OBJECTIVE: Wnt1 protein is the first factor in Wnt signaling
      pathway. It has been proven that high expression of Wnt1 protein was associated
      with malignant proliferation in many tumors. The aim of this study is to
      investigate the correlation between Wnt1 protein overexpression,
      clinicopathologic features and survival in resected non-small-cell lung cancer
      (NSCLC). METHODS: Immunohistochemical staining of Envision was applied to
      investigate the expression of Wnt1 protein in specimens of 115 NSCLC and 19
      benign pulmonary diseases. The correlation between the Wnt1 protein in specimens
      of 115 NSCLC and clinicopathologic features was analysed with chi2 test, and the
      correlation between the Wnt1 protein expression and the patient survival was
      evaluated with Kaplan-Meier survival curve and Cox regression. RESULTS: The
      positive rate ofWnt1 protein in specimens of NSCLC was 62.6%, which was
      significantly higher than 31.6% of benign pulmonary diseases (chi2 = 4.474, P =
      0.034). But it was not correlated with clinicopathologic features. Kaplan-Meier
      survival analysis and Log-rank test suggested that patients with Wnt1 protein
      overexpression had poor prognosis (P = 0.003). And Cox regression suggested Wnt1
      protein expression was an independent prognostic factor of NSCLC. CONCLUSION: The
      expression of Wnt1 was remarkably higher in specimens of resected NSCLC than that
      in benign pulmonary diseases. Overexpression of Wnt1 protein in NSCLC was
      correlated with prognosis and can be served as an independent prognostic factor
      of NSCLC.

PMID- 20681445
TI  - [Retrospective study of clinicopathological characteristics in bronchopulmonary
      carcinoid].
AB  - BACKGROUND AND OBJECTIVE: Bronchopulmonary carcinoid (BPC) account for less than
      2% of all primary lung malignant tumors, but few related studies were reported.
      The aim of this study is to analyze this rare disease's clinicopathological
      characteristics. METHODS: The clinical data of 28 patients with BPC in Cancer
      Center of Sun Yat-sen University, from January 1994 to June 2009, were enrolled
      into retrospective analysis. First, the corresponding paraffin blocks reexamined,
      slice up and stained, multiple pathologists re-consulted, and its subsets
      (typical carcinoid, TC; atypical carcinoid, AC) defined. Second, the clinical
      characteristics and immunohistochemical markers and its relationship with
      prognosis were analyzed. RESULTS: First, the 5-year survival for overall and TC,
      AC was 56% and 70%, 41% respectively in 28 cases. The markers CD99, Bcl-2 and Ki
      67 expression correlated significantly with the BPC subsets (P = 0.017, P =
      0.043, and P = 0.033 respectively). Further univariate analysis revealed that
      advanced TNM staging (P = 0.037), lymph node metastasis (P = 0.001) and Ki-67
      nucleolus's positive expression (P = 0.009) are poor prognostic factors. Second,
      the overall, TC, AC 5-year survival rate was 73%, 83%, 57% respectively in 20
      cases underwent the radically surgical resection. Further univariate analysis
      revealed that AC subset (P = 0.013), lymph node metastasis (P = 0.004) and Ki-67
      nucleolus's positive expression (P = 0.006), advanced TNM staging (P = 0.047) are
      poor prognostic factors in this 20 cases. Third, as univariate analysis, local
      recurrence and metastasis (n = 4) correlate significantly with Ki-67 nucleolus's
      and Bcl-2 positive expression (P = 0.027, 0.045, respectively). CONCLUSION: The
      prognosis of BPC was better than other types of primary lung cancer. Ki-67, Bcl-2
      high expression and advanced TNM staging are the poor recurrence and prognostic
      factors of BPC. The radical surgery remains the treatment of choice for
      resectable candidates in BPC as NSCLC.

PMID- 20681446
TI  - [Expression and its relationship of PRL-3 and RhoC in non-small cell lung
      cancer].
AB  - BACKGROUND AND OBJECTIVE: Phosphatase of regenerating liver-3 (PRL-3) is a newly
      identified protein-tyrosine phosphatase, which belongs to phosphatase of
      regenerating liver family, and plays a role in promoting tumor metastasis; Ras
      homologue C (RhoC) belongs to Rho subfamily of small-molecule G protein
      superfamily. However, the mechanisms of PRL-3 and RhoC are unknown. The aim of
      this study is to investigate the expressions of PRL-3 and RhoC proteins and their
      correlation to invasion and metastasis of non-small cell lung cancer (NSCLC),
      which may provide experiment evidence of the mechanism of PRL-3 in tumorigenesis
      and tumor-development. METHODS: Immunohistochemical staining was used to detect
      the expressions of PRL-3 and RhoC in NSCLC in 92 cases, and statistical methods
      were used to analyse statistical significances of their expressions in different
      groups and their correlation. RESULTS: The positive rates of PRL-3 and RhoC
      expressions in NSCLC were 69.6% (64/92) and 73.9% (68/92), respectively, and the
      expressions of PRL-3 and RhoC were closely correlated with TNM stage and
      lymphatic metastasis and pleural metastasis (P < 0.01), and they were correlated
      with each other (r = 0.754, P < 0.001). CONCLUSION: The expressions of PRL-3 and
      RhoC are higher in the higher TNM stage and lymphatic metastasis and pleural
      metastasis cases, and closely correlate with each other in NSCLC, which suggests
      that PRL-3 and RhoC might be in the same signal pathway and PRL-3 might promote
      the distant metastasis of cancer cell by RhoC and downstream factors.

PMID- 20681447
TI  - [K-RAS gene mutations in patients with non-small cell lung cancer].
AB  - BACKGROUND AND OBJECTIVE: Recent studies indicated that Non-small cell lung
      cancer (NSCLC) patients with mutant K-RAS failed to benefit from adjuvant
      chemotherapy, and the cancer did not respond to epidermal growth factor receptor
      (EGFR) tyrosine kinase inhibitors (TKIs). These findings indicated that K-RAS
      gene status can be a biomarker to predict the sensitivity of EGFR TKIs. The aim
      of this study is to analyze K-RAS gene mutations with NSCLC patients in Cancer
      Center of Sun Yet-sen University. METHODS: 52 fresh frozen tumor tissues were
      collected and K-RAS genes were amplified by PCR. Then PCR amplification fragments
      were sequenced and analyzed. RESULTS: Somatic mutations in the codon 12 of K-RAS
      gene in tumors were identified from 2 of 52 (3.8%) patients. There were no
      relationships among K-RAS gene mutations and gender, pathology, smoking,
      differentiation and stage. CONCLUSION: The frequency of K-RAS gene mutations with
      NSCLC in our center is very low and is similar to that in Asia patients, and is
      lower than that in Caucasian population.

PMID- 20681448
TI  - [Study on solitary pulmonary nodules: correlation between diameter and clinical
      manifestation and pathological features].
AB  - BACKGROUND AND OBJECTIVE: Solitary pulmonary nodules (SPN) is a knotty problem in
      clinical work. The clinical manifestation and pathological features of SPN in
      sizes may be obviously different. The aim of this study is to analyze the
      relationship between the diameters and clinicopathologic characteristics of SPN.
      METHODS: 390 patients (212 male, 178 female, ranging from 17 years to 86 years,
      median age 57.1 years) with SPN who were postoperatively diagnosed by pathology
      between Jan. 2000 and Jun. 2009 are enrolled to this study. In these cases, the
      number of SPN diameters which are smaller than 0.5 cm (including 0.5 cm) (group
      A) is 16, between 0.5 cm and 1 cm (including 1 cm, not including 0.5 cm) (group
      B) is 58, between 1 cm and 2 cm (group C) is 163, and between 2 cm and 3 cm
      (group D) is 153. The clinical manifestation, and postoperative pathological
      characters are analyzed in various diameter ranges. RESULTS: All procedures were
      carried out securely, including tumor enucleation (n = 20), wedge resection (n =
      153), lobectomy (n = 217). There are 130 benign cases (33.3%) and 260 malignant
      cases (66.7%). 58.5% SPN are detected incidently with no symptoms. There is an
      increasing incidence of clinical symptoms as the increasing diameter of SPN. All
      the cases are divided into 4 groups, the prevalence of malignant are separated
      43.7% (group A), 50.0% (group B), 63.2% (group C), 79.1% (group D). The diameter
      of SPN is positively correlated with incidence of malignancy (chi2 = 22.535, P <
      0.001). Single factor analysis and Logistic regression analysis show the diameter
      of SPN is an independent risk factor of malignant pathology (OR = 1.922, P <
      0.001). Fourteen patients in all of the SPN were followed up by 2 years or more
      before operation, and 10 of them turn out to be malignant at last. In the 14
      patients, 7 cases were found not enlarged by CT scan, and 3 of them (42.9%) were
      malignant. CONCLUSION: The diameter of SPN is highly associated with clinical
      symptoms, and is a significant risk factor to predict pathology. Early diagnosis
      and treatment is so important for patients with SPN.

PMID- 20681449
TI  - [Expression of transient receptor potential canonical channel proteins in human
      non-small cell lung cancer].
AB  - BACKGROUND AND OBJECTIVE: Transient receptor potential canonical (TRPC) proteins,
      a group of Ca2' permeable nonselective cation channels, are thought to constitute
      store-operated calcium channels (SOCC) and mediate store-operated calcium entry
      (SOCE) in various cell types. Members of TRPC have been found to be involved in
      abnormal proliferation, differentiation, and growth of cancer cells. The aim of
      this study is to detect the mRNA and protein expression of TRPC in non-small cell
      lung cancer (NSCLC). METHODS: Real-time quantitative PCRwas performed to screen
      the expression of TRPC mRNA in NSCLC tissue. Protein expression of TRPC was
      detected by Western blot. RESULTS: Among the seven family members of TRPC so far
      identified (TRPC1-7), we detected the expression ofTRPC1, TRPC3, TRPC4, TRPC6
      mRNA in 24 cases of NSCLC tissue; TRPC2, TRPC5 and TRPC7 mRNA were not
      detectable. The relative abundance of the expressed TRPC was TRPC1 approximately
      equal TRPC6 > TRPC3 > TRPC4. Western blot confirmed the protein expression of
      TRPC1, TRPC3, TRPC4 and TRPC6 in NSCLC tissue. CONCLUSION: Out of the seven
      members of TRPC, we found TRPC1, TRPC3, TRPC4, TRPC6 mRNA and protein were
      selectively expressed in human NSCLC tissue. This study could provide a basis for
      future exploration of the individual role of these TRPC proteins in mediating
      SOCE and in the progression of lung cancer.

PMID- 20681450
TI  - [Meta-analysis of the relationship between passive smoking population in China
      and lung cancer].
AB  - BACKGROUND AND OBJECTIVE: Studies of passive smoking exposure in China however
      are of particular interest, because of the high lung cancer rate in people who
      are mostly non-smokers. The aim of this study is to explore the relationship
      between passive smoking and lung cancer among non-smoking Chinese. METHODS: By
      searching Medline, PubMed, CENTRAL (the Cochrane central register of controlled
      trials), CBM, CNKI and VIP, et al, we collected both domestic and overseas
      published documents between 1987 and 2007 on passive smoking and lung cancer
      among non-smoking Chinese. Random or fixed effect models were applied to conduct
      meta-analysis on the case control study results, and the combined odds ratio (OR)
      and the 95% confidence interval (CI) were calculated as well. RESULTS: Sixteen
      documents were included into the combined analysis, which indicated that there
      was statistical significance between passive smoking and lung cancer (OR = 1.13,
      95% CI: 1.05-1.21, P = 0.001). It was significant of lung cancer among non
      smoking subjects associated with amount of tobacco passively smoked more than 20
      cigarettes daily, with life period in adulthood passive smoking exposure, with
      gender female, and with exposure to workplace. The P value, OR and 95% CI were P
      = 0.0003, OR = 1.78, 95% CI: 1.30-2.43; P = 0.0001, OR = 1.50, 95% CI: 1.23-1.83;
      P = 0.000 7, OR = 1.50, 95% CI: 1.19-1.90; P < 0.0001, OR = 1.41, 95% CI: 1.19
      1.66; respectively. And there was no significant difference between passive
      smoking and lung cancer with amount of tobacco passively smoked within 20
      cigarettes daily, with life period in childhood passive smoking exposure, with
      gender male and with exposure to spouse and parents. CONCLUSION: Passive smoking
      is an important risk factor of lung cancer among non-smoking Chinese, and for non
      smoking women who expose to environment tobacco smoke in a long period of time
      have a close relationship with lung cancer risk.

PMID- 20681451
TI  - [The clinical value of routine preoperative surgical staging to mediastinal lymph
      nodes on lung cancer].
AB  - BACKGROUND AND OBJECTIVE: The aim of this study is the clinical value of
      preoperative routine surgical staging to mediastinal lymph nodes on lung cancer.
      METHODS: Seventy-six cases underwent lymph nodes biopsy with mediastinoscopy. The
      diagnostic efficacy of thoracic CT scan and mediastinoscopy on mediastinal lymph
      nodes metastasis were compared. RESULTS: The sensitivity, specificity, accuracy,
      positive predictive value and negative predictive value of thoracic CT scan and
      mediastinoscopy on diagnosing mediastinal lymph nodes metastasis were 68.5%,
      66.7%, 68.4%, 84.6%, 16.7% and 87.5%, 100%, 84.2%, 100%, 60%, respectively.
      CONCLUSION: Routine preoperative mediastinoscopy had obvious advantage compared
      with thoracic CT scan on mediastinal lymph nodes staging. The routine
      preoperative surgical staging of mediastinal lymph nodes on lung cancer had high
      clinical value.

PMID- 20681452
TI  - [Diagnosis and treatment of tracheal or bronchuotracheal adenoid cystic
      carcinoma].
AB  - BACKGROUND AND OBJECTIVE: Adenoid cystic carcinoma is primary bronchopulmonary
      carcinoma with low malignancy, and 43 patients treated in the past 50 years in
      our hospital were retrospectively studied. The aim of this study is to discuss
      the clinical symptoms, pathologic characteristic and therapeutic method of
      primary tracheal or bronchuotracheal adenoid cystic carcinoma. METHODS: This
      study summarized total 43 patients of primary tracheal or bronchus adenoid cystic
      carcinoma treated in our hospital from Jan. 1958 to Dec. 2007. Among them, 40
      patients were treated by surgical resection, and 3 patients were treated by
      fiberoptic bronchoscope's interventional treatment. RESULTS: The 1-yr, 3-yr, 5-yr
      survival rates of the 43 patients above were 100% (41/41), 89.5% (34/38), 87.1%
      (27/31), respectively. CONCLUSION: Primary tracheal or bronchus adenoid cystic
      carcinoma are rare and low malignancy carcinoma. The clinical symptoms of them
      are not typical. The best treatment is early detection and taking measures of
      operation plus radiotherapy. The other palliative treatment is fiberoptic
      bronchoscope's interventional treatment.

PMID- 20681453
TI  - [Physicians' role in advancing tobacco control in China].

PMID- 20681454
TI  - [Current status and prospects of maintenance therapy in advanced stage non-small
      cell lung cancer].

PMID- 20681455
TI  - [Research progress on the relationship between insulin-like growth factor-I and
      lung cancer].

PMID- 20681456
TI  - [The location and molecular regulating mechanism of tracheal and lung stem
      cells].

PMID- 20681457
TI  - [Diagnostic significance of combining telomerase activity with CYFRA21-1 level in
      differentiating malignant pleural effusion caused by lung cancer from benign
      pleural effusion].
AB  - BACKGROUND AND OBJECTIVE Telomerase and CYFRA21-1 may be positively expressed in
      malignant pleural effusion, but the sensitivity and specificity of single tumor
      marker were low. The aim of this study is to investigate the diagnostic value of
      combining determination of telomerase activity and CYFRA21-1 levels in
      differentiating benign from malignant pleural effusion caused by lung cancer.
      METHODS: 80 patients with malignant and 50 patients with benign pleural effusion
      were enrolled into this study. The telomerase activity in pleural effusion was
      tested by means of telomeric repeat amplification protocal-PCR-ELISA (TRAP-PCR
      ELISA) and CYFRA21-1 levels were tested by the EIA method. All the results were
      analyzed by the statistical method. RESULTS: The levels of telomerase and CYFRA21
      1 in malignant pleural effusion was significantly higher than that in benign one
      (t = 17.252 and t = 13.951, P < 0.001). The sensitivity of telomerase activity
      testing for diagnosing malignant pleural effusion was 71.3%; the specificity was
      86.0% and the overall accuracy was 76.9%. The sensitivity of CYFRA 21-1 testing
      was 60.0%, the specificity was 78.0% and the overall accuracy was 66.9%. The
      sensitivity of the combined testing was 90.0%, the specificity was 76.0% and the
      overall accuracy was 86.9%. The sensitivity and the overall accuracy of combined
      testing were higher than those of telomerase and CYFRA21-1 testing single (chi2 =
      9.002 and chi2 = 19.201, P < 0.01; chi2 = 4.389 and chi2 = 14.647, P < 0.05).
      CONCLUSION: The combined testing oftelomerase with CYFRA21-1 can increase the
      sensitivity and overall accuracy of differential diagnosis of benign and
      malignant pleural effusion diagnosis.

PMID- 20681458
TI  - [A case report and literature review of small intestinal metastasis of large cell
      lung cancer].

PMID- 20681459
TI  - [Pulmonary hypertension--unusual complication of the bacterial overgrowth
      syndrome].

PMID- 20681460
TI  - [Is there circadian variation of big endothelin and NT-proBNP in patients with
      severe congestive heart failure?].
AB  - INTRODUCTION: Circadian rhytmus have long been recognized to occur in many
      biologic phenomena, including secretion of hormones as well as autonomic nervous
      system. There is increasing evidence that circadian rhythms have been also found
      in cardiovascular events, for example, myocardial infarction, sudden cardiac
      death as well as stroke have shown a circadian pattern of the distribution. The
      pathophysiology and the mechanism underlying these variations are the focus of
      much investigation, while i tis not full understood up to date. Heart rate, blood
      pressure, neurohumoral vasoactive factors, such as plasma norepinephrine levels
      and renin activity, and probably also contractility are increased in the morning
      hours. THE AIM OF OUR STUDY: To evaluate the circadian variability of plasma big
      endothelin and NT-proBNP level in patients with severe heart failure. PATIENTS:
      13 patients with severe heart failure, stable for at least one month, male/female
      -8/5, NYHA III/IV--11/2, mean left ventricle ejection fraction 23 +/- 5%, mean
      cardiothoracic ratio 59 +/- 7%, all treated with RAAS blocade (11 x ACE-I, 2x
      ARB), all treated with diuretics, 12 patients treated with beta-blockers, 7 with
      digoxin. The cause of heart failure was ischemic heart disease (9) or dilated
      cardiomyopathy (4). METHODS: Blood samples for big endothelin and NT-proBNP were
      taken every two hours during a standartised daily regime. RESULTS: Mean plasma
      level of big endothelin (ranging from 1.25 to 1.71 pmol/l) had significant
      diurnal variability (upper limit of normal values 0.7 pmol/l). Mean plasma level
      of NT-proBNP (ranging from 782 to 934 pmol/l) had no diurnal variability (upper
      limit of normal values of 350 pmo/l). SUMMARY: Plasma level of NT-proBNP is
      stable during 24 hours and shows no circadian variability. Plasma big endothelin
      showed a morning peak after a systematic increase during bed rest. NT-proBNP
      could be evaluated any time during the day, big endothelin sample should be taken
      during standartised condition.

PMID- 20681461
TI  - [The normalized smoothness index and parametric population RDH index of
      telmisartane in patients with newly diagnosed hypertension and metabolic
      syndrome].
AB  - INTRODUCTION: Ambulatory blood pressure monitoring provides an opportunity to
      evaluate 24-hour efficacy of once daily preparations. AIMS OF THE STUDY: To
      evaluate 24-hour efficacy of telmisartane in patients with newly diagnosed
      hypertension and metabolic syndrome using the parametric population RDH index and
      normalized smoothness index. PATIENT SAMPLE AND METHODOLOGY: Thirty newly
      diagnosed hypertonics with metabolic syndrome, sufficiently responding to blood
      pressure therapy with telmisartane, assessed using sphygmomanometer. Twenty six
      men, 4 women, mean age of 44 years, body mass index of 31.4 kg. m2, before and
      after 1 year of therapy. Blood pressure measured with sphygmomanometer and 24
      hour ambulatory monitoring (SpaceLabs 90207) according to the criteria of the
      European Society of Hypertension. Hypertension was defined as sphygmomanometer
      measured blood pressure values of more or equal to 130 and/or 85 mm Hg.
      Fulfilment of at least 3 criteria of metabolic syndrome according to the
      definition by The Adult Treatment Panel III. RESULTS: The population normalized
      smoothness index oftelmisartane (+/- standard error of the mean) of 1.00 +/- 0.11
      for systolic pressure and 0.84 +/- 0.10 for diastolic pressure. The parametric
      population RDH index of 24, 24, 0 for systolic pressure and 22, 15, 1 for
      diastolic pressure. CONCLUSION: Telmisartane at a mean dose of 60 mg once daily
      showed an adequate 24-hour efficacy in patients with newly diagnosed hypertension
      and metabolic syndrome responding to treatment, when blood pressure was measured
      using sphygmomanometer and the effect expressed as the parametric population RDH
      index and normalized smoothness index based on systolic blood pressure value. We
      did not prove the full 24-hour efficacy when diastolic blood pressure was used to
      calculate both indexes.

PMID- 20681462
TI  - [Essential thrombocythaemia and other myeloproliferative disorders with
      thrombocythaemia treated with Thromboreductin. A report from the database of
      register for the 1st quarter of 2010].
AB  - In the Czech Republic, anagrelid is used according to the recommendations of the
      Czech Working Group on Myeloproliferative Disorders for treatment
      ofthrombocythaemias associated with chronic myeloproliferative disorders--mainly
      essential thrombocythaemia and, regularly, reports are being presented from the
      Register of Patients Treated with Thromboreductin, most recently last year (Vnitr
      Lek 2009; 55: I-XII). The Register commenced in 2005 and from then it aims to
      determine detailed clinical and laboratory profiles of the patients. The
      structure of the Register has changed significantly in the course of its
      existence, reflecting the reports from each of the analyses conducted so far.
      Also, the data entry in the database improves every year and it reaches 97% on
      some of the items. The longest evaluation period in some of the patients is 108
      months. By April 2010, the Register database contained data on 717 patients. Of
      these, 672 patients with the diagnosis of a Ph-negative chronic
      myeloproliferative disorder were evaluated. This year's analysis included the
      patients with essential thrombocythaemia, polycythaemia vera and primary
      myelofibrosis only. The analysis included 418 women and 254 men with median age
      of50 years. Unlike the first years, 2/3 of the current sample are non pretreated
      patients, meaning that the patients reach the specialized centres early in their
      treatment. Also, patients, and the older patients in particular, are more
      frequently treated with combined regimens including Thromboreductin. We
      increasingly observe hypertension as one of the monitored risk factors preceding
      the disease and laboratory parameters showJAK2 mutation in more than a half of
      patients while some form ofthrombotic diathesis is found in the anamnesis of 7
      10% of patients. Some bleeding is observed in 1-5% of the registered patients. In
      comparison to the previous years, this is a decrease in the prevalence of
      clinical symptoms prior to the disease onset; this is very likely associated with
      an earlier patient diagnosis within the asymptomatic phase of the disease.
      Therapeutically, we achieve a fast treatment response but there still are 16.3%
      of sufficient afterone year of treatment. Thromboreductin dose is increasing but
      even in this group it does not exceeds the mean of 2.38 mg per 24 hours.
      Complications are observed in 6.2% of patients in the first year of therapy, and
      ofthese, thrombotic events in about 2.5% and (small) bleeding complications in 4%
      of patients. The data suggest that we still do not reach treatment response in a
      certain proportion of patients after a year of their therapy. Even though the
      care results from the analysed data improve every year, the Register helps to
      uncover some issues that still remain, such as treatment intensification and
      other treatment modifications.

PMID- 20681463
TI  - [Pulmonary hypertension--unusual complication of haemolysis and the bacterial
      overgrowth syndrome].
AB  - The authors describe a case of a patient with celiac disease in whom a secondary
      bacterial overgrowth had developed in the small intestine. Vitamin B12 and folic
      acid consumption deficiency resulted in a development of macrocytary anaemia and
      non-immune haemolysis. Subsequently, within a few weeks, a significant pulmonary
      hypertension has developed, the cause of which was first unclear. Haemolysis as
      well as pulmonary hypertension ceased following bacterial overgrowth treatment
      and B12 and, later on, folic acid substitution. Retrospectively, the authors
      infer that this could have been the haemolytic anaemia-associated pulmonary
      hypertension syndrome.

PMID- 20681465
TI  - [Hyperlipoproteinaemia and dyslipoproteinaemia I. Classification, diagnostics,
      cardiovascular, cardiometabolic and residual risk].
AB  - Cardiovascular diseases remain the most important cause of death worldwide. The
      situation in the Czech Republic is one of the best when compared to the other
      countries of the former socialist block; on the other hand, we significantly lack
      behind when the comparison is made to south and southwest European countries. The
      concept of risk factors (RF) and multifactorial character of atherosclerosis as
      the main cause of cardiovascular diseases (CVD) is fully accepted at present.
      Hyperlipoproteinaemia (HLP) and dyslipidemia (DLP) are a group of high incidence
      metabolic diseases characterised by increased levels of lipids and lipoproteins
      in plasma or, in case of DLP, by unsuitable, atherogenic composition of lipids
      and lipoproteins in plasma. HLP and DLP are among the most important RF for the
      development of CVD. Mainly LDL-cholesterol (LDL-C) is perceived as a very
      important risk factor; successful reduction of LDL-C is linked to a reduction in
      cardiovascular risk. Even when LDL-C is decreased and the so-called "target
      values" achieved, patients are still at risk ofa CV event. This remnant risk is
      the so called "residual risk". The most important "rival" to LDL-cholesterol
      among the risk factors is the metabolic syndrome, or rather the DLP associated
      with the metabolic syndrome, characterised from the perspective of DLP by low
      levels of HDL-cholesterol and increased triglycerides with concurrent occurrence
      of "small dense LDL". The issue of heterogeneity and atherogenicity oflipoprotein
      particles in general then becomes topical. Lipoprotein (a)--Lp(a) is another
      important lipid risk factor that is getting a significant attention.

PMID- 20681466
TI  - [BRNO Register 2: post-myocardial infarction pharmacotherapy].
AB  - We assessed 850 patients with a history of myocardial infarction >1 month ago who
      attended outpatient clinics of the Clinic of Internal Medicine and Cardiology at
      the Faculty Hospital Brno between 1st September 2009 and 31st December 2009.
      There were more men (650 vs. 200) and patients under 70 years of age (576 vs.
      264) in the cohort. 87.8% of patients experienced one myocardial infarction only
      and the mean age at the first infarction was 59.0 years in men and 65.5 in women
      (p < 0.001). 75.8% of patients had been prescribed all recommended
      pharmacotherapeutic groups according to guidelines (RAAS blockers, beta-blockers,
      statins, antiagregation agents) and each group individually was used in > 90% of
      patients. There were no differences between men and women and older and younger
      patients. ACE inhibitors and statins were not always prescribed in recommended
      (high) doses. Perindopril was the most frequently prescribed ACE inhibitor and
      atorvastatin the most frequently prescribed statin. Blood pressure of< 140/90 mm
      Hg was identified in 60.1% of patients, 75% of men and 65% of women had
      cholesterol level of <5 mmol/l and > 50% of patients had cholesterol < or = 4.5
      mmol/l, metabolic syndrome was found in about 1/2 of patients and smoking was
      admitted by 12.5% of patients.

PMID- 20681467
TI  - [Different courses of recurrent or multisystem Langerhans cells histiocytosis in
      adults--description of 22 cases from one centre].
AB  - Since its establishment in 1990, a total of 22 patients with confirmed Langerhans
      cell histiocytosis (LCH) have been monitored and treated at the Clinic of
      Internal Medicine Haemato-Oncology in Brno. In 5 patients, the disease was
      diagnosed in childhood and 2 of these 5 patients had late neurodegenerative
      changes in the CNS with a typical picture on MR and a typical PET-CT imaging
      fluorodeoxyglucose hypometabolism in the cerebellar area. In 5 patients from the
      cohort of 22, the disease had unifocal form, dominant in the area of skeleton
      with no recurrence after the treatment. However, in 12 patients, the disease
      affected a number of organs simultaneously (multifocal form of LCH). The aim of
      the description below is to characterise the monitored cohort of 22 patients and
      describe the very different courses of multifocal forms of LCH in 12 patients.

PMID- 20681468
TI  - [Sepsis and the septic shock in oncological or other immunocompromised patients-
      diagnosis, therapy].
AB  - Sepsis and the septic shock and the up to date knowledge about them represent a
      marked drifting for diagnostics and the treatment of this complications. Their
      application in patients with the oncological disease or the other
      immunocompromised patients represents further extension in the specific group of
      patients with several unique properties. In despite of the improving results in
      the oncological treatment there are only few reports in literature about this
      group of patients and this one is steadily growing due to the progressive
      improving of the supportive care in oncology. This group of patients with the
      febrile neutropenia and the sepsis (the most frequent complication) request the
      special focus of general practitioners and the internists because these ones are
      with these patients in contact as a first. They have to master the basal image
      about the specialties of this patient group. In our article we analyze this group
      of patients with focus on antibiotics in febrilie neutropenia and sepsis and on
      the other supportive care in the immunocopromised patients.

PMID- 20681469
TI  - [A psychological perspective on the problems faced by the oncology patients and
      their care teams].
AB  - Survey of the history and study of the psychical expressions of the oncology
      patients, the rules of communication ofoncologist and his patient. Personality of
      oncology patient and a Model of Kubler-Ross, then a decalogue of speaking about
      the oncology diagnosis. Clinical psychologict as an integral part of the medical
      team, which brings a supportive care for the oncology patients, then the
      psychopatological behaviour appears iside a medical team. In the end there are
      the authentic patients stories with the psychologist commentary.

PMID- 20681470
TI  - [Prophylactic antibiotics and probiotics in acute pancreatitis].
AB  - Severe acute pancreatitis is serious disease. High mortality is also due to
      infection complications. If we will be able to prevent the infection, it could
      diminish mortality. The role of prevention of infection with antibiotics and
      probiotics is discussed in the paper.

PMID- 20681471
TI  - [The value of various imaging techniques in diagnosing and monitoring the disease
      activity of multiple myeloma].
AB  - Imaging techniques such as RTG, CT, MR and PET are key in diagnosing multiple
      myeloma. Their selection, combinations and sequence of their application are
      important for early and correct diagnosis. It is the clinical experience with
      this condition complemented by suitable imaging diagnostics that leads effective
      treatment.

PMID- 20681472
TI  - [Contribution to the evaluation of serum levels of selected biological parameters
      in monoclonal gammopathy of undetermined significance and in individual clinical
      stages of multiple myeloma].
AB  - INTRODUCTION: This study aimed to measure serum levels of 12 selected parameters
      in patients with monoclonal gammopathy of undetermined significance (MGUS) and
      initial, asymptomatic phase of multiple myeloma (MM) to assess their potential
      benefit in differentiating both conditions. PATIENT SAMPLE AND METHODOLOGY: The
      analysed sample of 131 patients consisted of 62 patients with MGUS and 69
      patients with MM fulfilling the criteria of the International Myeloma Working
      Group (IMWG). The following techniques were used to assess serum levels:
      quantitative immunoradiometry (bone-type alkaline phosphatase - bALP and insulin
      like growth factor-1 - IGF-1), chemiluminescent enzyme immunochemical reaction
      (parathormone--PTH), quantitative sandwich enzyme immunoassay (osteopontin--OPN,
      endostatin (ES), macrophage inflammatory protein-1alpha/beta--MIP-1alpha/beta,
      angiogenin--ANG a IL-17). Pearson chi2 test and Mann-Whitney U-test were applied
      during the statistical analysis. RESULTS: The analysis showed statistically
      significant differences in serum concentrations between MGUS and symptomatic form
      of MM (Durie-Salmon (D-S) stage 2-3) for: albumin, beta2-microglobulin (beta2-M)
      and OPN (p = 0.0001 and < 0.0001); osteocalcin for stage 2 (p = 0.006) and MIP
      1alpha for stage 3 patients (p = 0.0002). Using the International Staging System
      (ISS), statistically significant differences between MGUS and all stages of MM (1
      3) were identified for albumin and OPN (p = 0.003 and 0.001 and 0.00009,
      respectively), stages 2 and 3 for beta2-M and ES (p = 0.015 and 0.0001,
      respectively), stage 2 for ANG (p = 0.014) and stage 3 for MIP-1alpha (p =
      0.00001). Statistically significant differences between MGUS and initial,
      asymptomatic phase of MM (D-S stage 1) was found only for bALP (p = 0.01) and for
      albumin (p = 0.004) and OPN (p = 0.003) when ISS was applied. Renal function
      impairment (D-S substage B) showed in comparison to MGUS significant elevation of
      serum levels of beta2-M (p < 0.0001), OC (p = 0.011), IGF-1 (p = 0.014), OPN (p =
      0.003), ES (p = 0.0001), MIP-1alpha (p = 0.0004) and ANG (p = 0.005) and for
      albumin (p < 0.0001), beta2-M (p < 0.0001) and OPN (p < 0.0001) only when
      compared to substage A. CONCLUSION: Only albumin and OPN showed useful even
      though non-specific potential to differentiate MGUS from all ISS stages of MM,
      beta2-M and ES for ISS stages 2 and 3, the other parameters differed for stage 2
      (ANG), stage 3 (MIP-1alpha) only and stage 1 (bALP), stage 2 (OC) and stage 3
      (MIP-1alpha) when D-S stratification was applied.

PMID- 20681473
TI  - [Continuous monitoring of tissue glucose].
AB  - Continuous glucose monitoring is technology revolution in diabetology similar to
      holter ECG monitoring in cardiology. With goal of the diabetes treatment to
      achieve almost normal glucose concentration in blood, continuous glucose
      monitoring can help in hypoglycemia risk reduction. Continuous glucose monitoring
      offers actual value of glycemia longitudinal whole day, with possibility of
      analyzing records and signalization when programmed thresholds are exceeded. It
      offers immediate patients reaction by modification of insulin treatment, food
      intake or physical activity, and also retrospective analysis of records.
      Subsequently it is possible to improve long-term treatment. Special contribution
      of continuous glucose monitoring is in recognizing undetectable hypoglycemias,
      especially during sleep.

PMID- 20681474
TI  - [The value of baroreflex sensitivity for cardiovascular risk stratification in
      hypertensives].
AB  - Impaired baroreflex sensitivity (BRS) is a marker of autonomous dysfunction,
      which may play an important role in the long-term development of arterial
      hypertension, disease progression as well as complications related to global
      cardiovascular risk. The aim of the study was to evaluate the clinical
      significance of baroreflex sensitivity in hypertensives with/without major
      cardiovascular events. We found out that essential hypertension is associated
      with decreased BRS, and that grade of hypertension is inversely related to BRS
      values. Spontaneous BRS values in hypertensives with major cardiovascular event
      (stroke, myocardial infarction) were significantly lower even 6 months and more
      after myocardial infarction and stroke onset compared to remaining patients (p <
      0.05). BRS is a clinically applicable, noninvasive method for assessing early
      dysfunction of autonomic nervous system, which seems to be an additive emerging
      marker of cardiovascular risk stratification in hypertensive patients.

PMID- 20681475
TI  - [Prevention and treatment of extremity vascular ischemic disease].
AB  - Extremitovascular ischemic disease (peripheral arterial disease of extremities -
      PAD) is an important manifestation of systemic atherosclerosis and other arterial
      diseases of vascular system. The lower the anklebrachial pressure index, the
      greater the risk of serious cardiovascular events (e.g., acute myocardial
      infarction, stroke). Prevention and treatment ofextremitovascular disease is
      discussed in this article.

PMID- 20681476
TI  - [Changes in lipoprotein spectrum in patients with the diagnosis of extremity
      vascular ischemic disease].
AB  - New method of lipoprotein determination on polyacrylamid gel with Lipoprint LDL
      system quantifies non atherogenic and atherogenic plasma lipoproteins, including
      small dense LDL, the potent atherogenic lipoprotein subpopulations. According to
      majority of non atherogenic versus atherogenic lipoprotein in the whole
      lipoprotein spectrum, this method distinguishes a non atherogenic lipoprotein
      profile phenotype A from an atherogenic lipoprotein profile phenotype B.
      Definitely, the contribution of this method is focusing on the atherogenic
      lipoprotein profile phenotype B in 80% of patients with an extremito-vascular
      ischemic disease and on the existence of control subgroup ofnormolipemic subjects
      with an atherogenic lipoprotein profile (7% ofprobands of control group). These
      persons represent a risk population. Till now, the facilities for identifying of
      these "normolipemic persons at risk" are limited.

PMID- 20681477
TI  - [Universities need to have high quality education as well as an effective quality
      control of their students' (products') knowledge and skill base].
AB  - In order for the schools of medicine to produce high quality physicians, they
      have to provide high quality education as well as they must ensure that knowledge
      building is taking place in the course of the programme and that the students
      whose efforts and/or abilities do not allow achievement of the required criteria
      are eliminated. Exams used to be the standard quality control tool. However,
      current information technologies allow doubling-up of this control; retaining the
      traditional examinations but preceding them with the requirement to complete
      multiple-choice tests. The text summarizes our experience with examining the
      students' mental presence during teaching with tests and our plans for the
      combined form of exit control using tests, completion of which will be
      prerequisite to admission to the exam itself. We do not believe that tests should
      completely replace exams but we do believe that the requirement to pass the exam
      should only take place following previous successful completion ofa test. This is
      achievable ifwe manage to establish a computer teaching room, i.e. examination
      room, and transform a vast number of questions into high quality multiple choice
      tests.

PMID- 20681478
TI  - Discovering breast cancer drug candidates from biomedical literature.
AB  - We developed a new paradigm with the ultimate goal of enabling disease-specific
      drug candidate discovery with molecular-level evidences generated from literature
      and prior knowledge. We showed how to implement the paradigm by building a
      prototype literature-mining framework and performing drug-protein association
      mining for breast cancer drug discovery. In a molecular pharmacology study of
      breast cancer, 79.2% of 729 enriched drugs in 'Organic Chemicals' category were
      validated to be disease-related, and the remaining 20.8% were also investigated
      as potential for future molecular therapeutics studies. 'Doxorubicin',
      'Etoposide' and 'Paclitaxel' were identified as having similar pharmacological
      profiles to treat breast cancer.

PMID- 20681479
TI  - Detecting distant homologies on protozoans metabolic pathways using scientific
      workflows.
AB  - Bioinformatics experiments are typically composed of programs in pipelines
      manipulating an enormous quantity of data. An interesting approach for managing
      those experiments is through workflow management systems (WfMS). In this work we
      discuss WfMS features to support genome homology workflows and present some
      relevant issues for typical genomic experiments. Our evaluation used Kepler WfMS
      to manage a real genomic pipeline, named OrthoSearch, originally defined as a
      Perl script. We show a case study detecting distant homologies on trypanomatids
      metabolic pathways. Our results reinforce the benefits of WfMS over script
      languages and point out challenges to WfMS in distributed environments.

PMID- 20681480
TI  - Mining the protein data bank with CReF to predict approximate 3-D structures of
      polypeptides.
AB  - n this paper we describe CReF, a Central Residue Fragment-based method to predict
      approximate 3-D structures of polypeptides by mining the Protein Data Bank (PDB).
      The approximate predicted structures are good enough to be used as starting
      conformations in refinement procedures employing state-of-the-art molecular
      mechanics methods such as molecular dynamics simulations. CReF is very fast and
      we illustrate its efficacy in three case studies of polypeptides whose sizes vary
      from 34 to 70 amino acids. As indicated by the RMSD values, our initial results
      show that the predicted structures adopt the expected fold, similar to the
      experimental ones.

PMID- 20681481
TI  - On a novel coalescent model for genome-wide evolution of copy number variations.
AB  - Since we are limited in our knowledge of human demographic history and variations
      of recombination and mutation rates, large-scale computer simulation is a
      necessary tool in genetics. Here we propose and computationally simulate a model
      of evolution for unique and segmentally duplicated regions of human genome. Since
      such segmentally duplicated regions show a complex behaviour of copy number
      changes, our model will hopefully lead to a better understanding of the
      evolutionary developments of CNVs, algorithms for associations studies with CNV
      markers, and finally, for characterising parameters for stochastic diffusion
      models, describing asymptotic behaviour of evolutionary processes.

PMID- 20681482
TI  - Using hybrid hierarchical K-means (HHK) clustering algorithm for protein sequence
      motif super-rule-tree (SRT) structure construction.
AB  - Many algorithms or techniques to discover motifs require a predefined fixed
      window size in advance. Because of the fixed size, these approaches often deliver
      a number of similar motifs simply shifted by some bases or including mismatches.
      To confront the mismatched motifs problem, we use the super-rule concept to
      construct a Super-Rule-Tree (SRT) by a modified Hybrid Hierarchical K-means (HHK)
      clustering algorithm, which requires no parameter set-up to identify the
      similarities and dissimilarities between the motifs. By analysing the motif
      results generated by our approach, they are significant not only in sequence area
      but also in secondary structure similarity.

PMID- 20681483
TI  - A weighted local least squares imputation method for missing value estimation in
      microarray gene expression data.
AB  - Many clustering techniques and classification methods for analysing microarray
      data require a complete dataset. However, very often gene expression datasets
      contain missing values due to various reasons. In this paper, we first propose to
      use vector angle as a measurement for the similarity between genes. We then
      propose the Weighted Local Least Square Imputation (WLLSI) method for missing
      values estimation. Numerical results on both synthetic data and real microarray
      data indicate that WLLSI method is more robust. The imputation methods are then
      applied to a breast cancer dataset and interesting results are obtained.

PMID- 20681484
TI  - LIBGS: a MATLAB software package for gene selection.
AB  - Many gene selection algorithms have been applied in gene expression data analysis
      successfully. To solve different developing environments of these toolkits, such
      as rankgene (Su et al., 2003), and mRMR
      (http://research.janelia.org/peng/proj/mrmr/index.htm), perform data analysis and
      make algorithm comparison more flexible, we have developed a software package
      LIBGS including: 1) Seven new gene selection algorithms implemented using MATLAB.
      2) MATLAB interface for Rankgene. 3) MATLAB interface for LIBSVM and WEKA. 4)
      Programs for converting data formats. 5) A collection of six popular gene
      expression data sets. These features make LIBGS a useful tool in gene expression
      analysis and feature selection.

PMID- 20681485
TI  - The effect of patient age on perceived resuscitation outcomes by practitioners.
AB  - BACKGROUND: When health care practitioners assist patients with decisions about
      advance directives, the risks and benefits of resuscitation options are often
      discussed. Whether practitioners have accurate perceptions about in-hospital
      resuscitation success rates is not known, nor is the effect of patient age on
      these perceptions. Age on its own has not been definitively associated with
      decreased inpatient survival after resuscitation. The goal of this study was to
      compare perceived resuscitation success rates with the actual observed rates at
      our hospital and to assess the effect of patient age on the perceived rates.
      METHODS: A survey-based observational study of on-duty hospital-based faculty,
      internal medicine resident physicians, and critical care nurses was performed
      over a week-long recruitment period to estimate their perception of in-hospital
      resuscitation success rates for patients of different ages. The survey response
      rate was 100%. RESULTS: Patient survival to hospital discharge following in
      hospital resuscitation during a three-year period at New Hanover Regional Medical
      Center was 29.22% for patients < 70 years old and 20.13% for patients > or = 70.
      The perceived in-hospital resuscitation success rates were 38.76% for patients <
      70 and 21.24% for patients > or = 70. This corresponds to a statistically
      significant overestimation of resuscitation success rates for patients < 70 years
      old (p < 0.001), although predictions were fairly accurate for patients > or =
      70. When posed with one of two clinical scenarios where the only different
      variable was patient age, participants were statistically more likely to predict
      success for the younger patient. Subgroup analysis showed general agreement in
      the estimates between the three major types of practitioners, and factors such as
      length of experience in their current position and time since their last Advanced
      Cardiac Life Support (ACLS) recertification course did not have a significant
      impact on these perceptions. CONCLUSIONS: Practitioners may overestimate
      resuscitation success rates in patients younger than 70. Disseminating
      information about ACLS success rates to clinicians, and what factors affect or do
      not affect these rates, seems essential.

PMID- 20681486
TI  - Disparities in colorectal cancer stage of diagnosis among Medicaid-insured
      residents of North Carolina.
AB  - OBJECTIVE: To evaluate the individual and community factors correlated with local
      disease among the North Carolina Medicaid-insured population diagnosed with
      colorectal cancer between 7998 and 2002. METHODS: North Carolina residents
      diagnosed with first primary, SEER-staged colorectal cancer between 1998-2002 and
      enrolled in Medicaid were included in this study. Secondary data from the North
      Carolina Central Cancer Registry linked to Medicaid claims were utilized for this
      study. Descriptive and logistic regression analyses were conducted. RESULTS: One
      out of every three individuals insured by Medicaid with colorectal cancer between
      1998 and 2002 in North Carolina were diagnosed with local stage disease. Factors
      associated with increased likelihood of diagnosis with local disease included age
      > or = 65 (OR = 1.48, 95% CI, 1.27-7.72) and living in an urban area (OR = 1.19,
      95% CI, 7.03-1.36). Persons with race defined as non-white and non-black were
      significantly less likely than non-Latino whites to be diagnosed with local
      disease (OR = 0.49, 95% CI, 0.27-0.97). LIMITATIONS: Reliance on secondary data
      limits the utility of data regarding factors contributing to late-stage
      diagnosis. CONCLUSIONS: Interventions to increase early diagnosis of colorectal
      cancer among the Medicaid-insured are needed. More research is needed to confirm
      and explain our finding that individuals <65 years of age and persons living in
      rural areas insured by Medicaid are more likely to be diagnosed at a later stage.
      The benefit of aging into Medicare among the Medicaid-insured population needs
      further elucidation.

PMID- 20681487
TI  - What does health reform mean for North Carolina?

PMID- 20681488
TI  - Understanding health reform: a work in progress.

PMID- 20681489
TI  - Health reform: provisions for immediate implementation.

PMID- 20681490
TI  - On the constitutionality of health care reform.

PMID- 20681491
TI  - Federal health care reform legislation establishes consumer protections, health
      insurance exchanges.

PMID- 20681492
TI  - What does the temporary national high risk pool mean for North Carolina?

PMID- 20681493
TI  - Health reform impacts and improvements affecting Medicare beneficiaries.

PMID- 20681494
TI  - North Carolina's safety net in the new world of health reform.

PMID- 20681495
TI  - Health reform's effect on school-based health centers.

PMID- 20681496
TI  - Health reform and workforce: the North Carolina connection.

PMID- 20681497
TI  - The National Health Service Corps--a critical component of provider recruitment
      in North Carolina's rural and underserved communities.

PMID- 20681498
TI  - Information technology reform IS health reform.

PMID- 20681499
TI  - Prevention in health care reform: the time has come.

PMID- 20681500
TI  - Comparative effectiveness research in the era of health reform.

PMID- 20681501
TI  - Spending limited health care dollars on what works best: the promise of
      comparative effectiveness research.

PMID- 20681502
TI  - Reform speeds up an already accelerating transformation: the effect on health
      care quality.

PMID- 20681503
TI  - Implementing national health reform in North Carolina.

PMID- 20681504
TI  - Health reform: funding provisions.

PMID- 20681505
TI  - North Carolina nurse-family partnership: evidence-based nurse home visitation
      program and health care reform.

PMID- 20681506
TI  - Projected changes in North Carolina health insurance coverage due to health
      reform.

PMID- 20681507
TI  - Health prevention.

PMID- 20681508
TI  - Comparison of 18F PET and 99mTc SPECT imaging in phantoms and in tumored mice.
AB  - Our objective was to compare the performance of a micro-single photon emission
      computed tomography (micro-SPECT) with that of a micro-positron emission
      tomography (microPET) in a Her2+ tumored mice using an anti-Her2 nanoparticle
      radiolabeled with (99m)Tc and (18)F. Camera performance was first compared using
      phantoms; then a tumored mouse administered the (99m)Tc-nanoparticle was imaged
      on a Bioscan NanoSPECT/CT, while another tumored mouse received the identical
      nanoparticle, labeled now with (18)F, and was imaged on a Philips Mosaic HP PET
      camera. The nanoparticle was radiolabeled with (99m)Tc via MAG(3) chelation and
      with (18)F via SFB as an intermediate. Phantom imaging showed that the resolution
      of the SPECT camera was clearly superior, but even with 4 heads and multipinhole
      collimators, detection sensitivity was 15-fold lower. Radiolabeling of the
      nanoparticle by chelation with (99m)Tc was considerably easier and safer than
      manual covalent attachment of (18)F. Both cameras provided accurate quantitation
      of radioactivity over a broad range. In conclusion, when deciding between (99m)Tc
      vs (18)F, an advantage rests with the chelation of (99m)Tc over covalent
      attachment of (18)F, achieved manually or otherwise, but with these small animal
      cameras, this choice also results in trading lower sensitivity for higher
      resolution.

PMID- 20681509
TI  - Drug discovery with DNA-encoded chemical libraries.
AB  - DNA-encoded chemical libraries represent a novel avenue for the facile discovery
      of small molecule ligands against target proteins of biological or pharmaceutical
      importance. Library members consist of small molecules covalently attached to
      unique DNA fragments that serve as amplifiable identification barcodes. This
      encoding allows the in vitro selection of ligands at subpicomolar concentrations
      from large library populations by affinity capture on a target protein of
      interest, in analogy to established technologies for the selection of binding
      polypeptides (e.g., antibodies). Different library formats have been explored by
      various groups, allowing the construction of chemical libraries comprising up to
      millions of DNA-encoded compounds. Libraries before and after selection have been
      characterized by PCR amplification of the DNA codes and subsequent relative
      quantification of library members using high-throughput sequencing. The most
      enriched compounds have then been further analyzed in biological assays, in the
      presence or in the absence of linked DNA. This article reviews experimental
      strategies used for the construction of DNA-encoded chemical libraries, revealing
      how selection, decoding, and hit validation technologies have been used for drug
      discovery programs.

PMID- 20681510
TI  - Distinguishing diffusional and plant control of Cd and Ni uptake by
      hyperaccumulator and nonhyperaccumulator plants.
AB  - This work set out to test the hypothesis that uptake of metals by
      hyperaccumulator (HA) plants is more likely to be diffusion limited than uptake
      by nonhyperaccumulator (NHA) plants. Two circumneutral soils, with different
      contents of organic matter (0.8 and 5.8%), were amended with Cd (0.5 to 5 mg kg(
      1)) and Ni (10 to 100 mg kg(-1)). A Cd HA plant, Thlaspi caerulescens, was grown
      in pots containing the Cd amended soils, and a Ni HA, Thlaspi goesingense, was
      grown in pots containing the Ni amended soils. A NHA plant of the same family,
      Thlaspi arvense, was grown in the same soils. Metals were measured in both roots
      and shoots of all plants. Concentrations of Cd and Ni were measured in soil
      solution and using the technique of diffusive gradients in thin-films (DGT). The
      dependencies of metal measured by DGT, [M]DGT, and in soil solution, [M]ss, on
      the amended metal concentration, [M]add, were consistent with fast supply of Cd
      but a slower rate of release of Ni from solid phase to solution at lower [Ni]add.
      Detailed consideration of the dependence of Ni and Cd in shoots and roots on
      [M]add, [M]ss, and [M]DGT allowed assessment of the supply mechanism. The weight
      of evidence suggested that diffusion limitation applies for uptake of Cd by both
      HA and NHA plants and for uptake of Ni by the HA. However, uptake of Ni by the
      NHA is not limited by diffusion and the biotic ligand model is probably
      appropriate.

PMID- 20681511
TI  - Impact of knowledge and misconceptions on benefit and risk perception of CCS.
AB  - Carbon Dioxide Capture and Storage (CCS) is assumed to be one of the key
      technologies in the mitigation of climate change. Public acceptance may have a
      strong impact on the progress of this technology. Benefit perception and risk
      perception are known to be important determinants of public acceptance of CCS. In
      this study, the prevalence and effect of cognitive concepts underlying
      laypeople's risk perception and benefit perception of CCS were examined in a
      representative survey (N=654) in Switzerland. Results confirm findings from
      previous qualitative studies and show a quantification of a variety of widespread
      intuitive concepts that laypeople hold about storage mechanisms as well as about
      leakage and socioeconomic issues, which all appeared to influence risk perception
      and benefit perception. The perception of an overpressurized reservoir and
      concerns about diffuse impacts furthermore amplified risk perception. Appropriate
      images about storage mechanisms and climate change awareness were increasing the
      perception of benefits. Knowledge about CO2 seemed to lower both perceived
      benefits and perceived risks. Implications for risk communication and management
      are discussed.

PMID- 20681512
TI  - An Asia-specific source of dechlorane plus: concentration, isomer profiles, and
      other related compounds.
AB  - The distribution of dechloranes, a group of chlorinated flame retardants, were
      investigated in air, soil, and sediment around a newly discovered Dechlorane Plus
      (DP) production facility in China (Anpon). To date, the only known DP
      manufacturing plant is located in Niagara Falls, NY (OxyChem). Dechloranes
      including DP, Dechlorane (Mirex), and the recently discovered Dechlorane 602 (Dec
      602) were detected in air, soil, and sediment, while Dechlorane 603 and
      Dechlorane 604 were below detection limit in all matrices. DP air concentrations
      near the facility ranged from 7737 to 26 734 pg m(-3), the greatest reported thus
      far. Soil concentrations in the same area for DP, Dechlorane, and Dec 602 were
      1490+/-3580 ng g(-1), 81.6+/-96.5 ng g(-1), and 7.24+/-13.2 ng g(-1) dry weight,
      respectively. Interestingly, lower concentrations of DP (4.93+/-4.34 ng g(-1)),
      Dechlorane (30.2+/-19.9 ng g(-1)), and Dec 602 (2.14+/-2.23 ng g(-1)) were found
      in sediment from a nearby canal. Spatial trends of Dechlorane and Dec 602 in soil
      were similar to DP, implying that the DP manufacturing plant may also be a source
      of these other flame retardants. DP soil concentrations surrounding the facility
      decreased by an order of magnitude within 7.5 km. The syn-DP fractional abundance
      (fsyn) value (0.40) for the commercial DP product manufactured at Anpon was
      slightly higher than that (0.20-0.36) produced by OxyChem. The fsyn value in most
      air samples was largely similar to the Chinese commercial DP mixture, while most
      soil and sediment abundances were lower, suggesting a stereoselective depletion
      of syn-DP.

PMID- 20681513
TI  - Redox-magnetohydrodynamic microfluidics without channels and compatible with
      electrochemical detection under immunoassay conditions.
AB  - A unique capability of redox-magnetohydrodynamics (redox-MHD) for handling
      liquids on a small scale was demonstrated. A 1.2 muL solution plug was pumped
      from an injection site to a detector without the need for a channel to direct the
      flow. The redox pumping species did not interfere with enzymatic activity in a
      solution compatible with enzyme-linked immunoassays. Alkaline phosphatase (AP), a
      common enzyme label, converted p-aminophenyl phosphate (PAPP) to p-aminophenol
      (PAP(R)) in the presence of 2.5 mM Ru(NH(3))(6)Cl(2) and 2.5 mM Ru(NH(3))(6)
      Cl(3), in 0.1 M Tris buffer (pH = 9). A solution plug containing PAPP (no AP) was
      pumped through the surrounding solution containing AP (no PAPP), and the
      enzymatically generated PAP(R) was easily detected and distinguishable
      electrochemically from the pumping species with square wave voltammetry down to
      0.1 mM concentrations. The test device consisted of a silicon chip containing
      individually addressable microband electrodes, placed on a 0.5 T NdFeB permanent
      magnet with the field oriented perpendicular to the chip. A 8.0 mm wide x 15.5 mm
      long x 1.5 mm high volume of solution was contained by a poly(dimethylsiloxane)
      gasket and capped with a glass slide. A steady-state fluid velocity of
      approximately 30 mum/s was generated in a reinforcing flow configuration between
      oppositely polarized sets of pumping electrodes with approximately 2.1 muA.

PMID- 20681515
TI  - Analysis of protein-small molecule interactions by microscale equilibrium
      dialysis and its application as a secondary confirmation method for on-bead
      screening.
AB  - On-bead screening of one-bead one compound (OBOC) libraries is an ultra fast
      surface based primary high-throughput screening (HTS) method. Typically the
      binding of a tagged target protein to bead immobilized compounds or its altered
      enzymatic activity are detected. For an efficient and reliable ligand discovery
      process secondary assays to confirm on-bead compound activity in homogeneous
      solution are key to exclude artifacts and weak binders. Ideally they should allow
      to flag hit compounds with undesirable biophysical properties such as
      aggregation, unspecific binding, or insufficient solubility and the like. Here we
      demonstrate that miniaturized and parallelized equilibrium dialysis is an
      excellent and generic secondary confirmation method for hit compounds identified
      by on-bead screening. We further show that microscale dialysis can be reliably
      performed prior to decoding and resynthesis even with hit-compounds cleaved from
      the single beads. Down-scaling of the method takes advantage of the fluorescent
      tag, AIDA, which is integrated as permanent tracer in our library design. Our
      results suggest that microscale equilibrium dialysis followed by high performance
      liquid chromatography (HPLC) analysis is a generic, cheap, and meaningful
      confirmation method for identifying the most promising candidates within a series
      hit compounds derived from fluorescently tagged one-bead one-compound libraries.

PMID- 20681516
TI  - Efficient assembly of 1-methylene-1H-indenes via palladium-catalyzed tandem
      reaction of 1-(2,2-dibromovinyl)-2-alkenylbenzene with arylboronic acid.
AB  - Highly efficient palladium-catalyzed reaction of 1-(2,2-dibromovinyl)-2
      alkenylbenzene with arylboronic acid is disclosed, which generates the
      functionalized 1-methylene-1H-indenes in good yields. Tandem Suzuki-Miyaura
      coupling and Heck reactions are involved in this process.

PMID- 20681514
TI  - Combinations of affinity-enhancing mutations in a T cell receptor reveal highly
      nonadditive effects within and between complementarity determining regions and
      chains.
AB  - Understanding the energetic and structural response to multiple mutations in a
      protein-protein interface is a key aspect of rational protein design. Here we
      investigate the cooperativity of combinations of point mutations of a T cell
      receptor (TCR) that binds in vivo to HLA-A2 MHC and a viral peptide. The
      mutations were obtained from two sources: a structure-based design study on the
      TCR alpha chain (nine mutations) and an in vitro selection study on the TCR beta
      chain (four mutations). In addition to combining the highest-affinity variants
      from each chain, we tested other combinations of mutations within and among the
      chains, for a total of 23 TCR mutants that we measured for binding kinetics to
      the peptide and major histocompatibility complex. A wide range of binding
      affinities was observed, from 2- to 1000-fold binding improvement versus that of
      the wild type, with significant nonadditive effects observed within and between
      TCR chains. This included an amino acid-dependent cooperative interaction between
      CDR1 and CDR3 residues that are separated by more than 9 A in the wild-type
      complex. When analyzing the kinetics of the mutations, we found that the
      association rates were primarily responsible for the cooperativity, while the
      dissociation rates were responsible for the anticooperativity (less-than-additive
      energetics). On the basis of structural modeling of anticooperative mutants, we
      determined that side chain clash between proximal mutants likely led to
      nonadditive binding energies. These results highlight the complex nature of TCR
      association and binding and will be informative in future design efforts that
      combine multiple mutant residues.

PMID- 20681517
TI  - Alternative experimental design with an applied normalization scheme can improve
      statistical power in 2D-DIGE experiments.
AB  - 2D-DIGE experiments are a high-throughput technique for measuring protein
      abundances based on gel separation. Traditionally three samples are multiplexed
      per gel: two biological test samples and a third internal standard sample
      consisting of a pool of all test samples. We demonstrate that the use of an
      internal standard helps to account for technical variation caused by spatial
      intensity biases that exist in the gels and propose a novel data-preprocessing
      technique, a spatial intensity bias removal (SIBR), which can approximate these
      biases using only the data of biological replicates loaded on the gel. Using this
      technique, we show that by replacing the internal standard with additional
      biological replicates, a significant increase in statistical power can be
      achieved compared to traditional 2D-DIGE designs. This boost in statistical power
      can be used to reduce the false positive rate for identifying differential
      protein abundances without compromising sensitivity, or to improve sensitivity
      without compromising false positive rate. A software implementation of SIBR can
      be downloaded at http://ibiza.biw.kuleuven.be/SIBR .

PMID- 20681518
TI  - Nonplanar, noninnocent, and chiral: a strongly saddled metallocorrole.
AB  - The first crystal structure of a copper beta-octabromo-meso-triarylcorrole
      exhibits a uniquely saddled corrole macrocycle, where adjacent pyrrole rings are
      tilted relative to each other by 60-80 degrees. Such strong nonplanarity may be
      contrasted with the essentially planar macrocycle conformations observed in the
      vast majority of metallocorrole crystal structures. Density functional theory
      calculations suggest that two effects, ligand noninnocence and peripheral
      overcrowding, acting in concert, are responsible for the unique, observed
      conformation.

PMID- 20681519
TI  - Identification of carbonic anhydrase I immunodominant epitopes recognized by
      specific autoantibodies which indicate an improved prognosis in patients with
      malignancy after autologous stem cell transplantation.
AB  - This work employs an epitope mapping of carbonic anhydrase (CA), isoform I (CA
      I), for detection of the main immunodominant epitopes. Our interest has arisen
      from an observed spontaneous tumor regression in patients who developed an
      aplastic anemia type syndrome after a high-dose therapy with autologous stem cell
      transplantation and whose sera contained high titer of anti carbonic anhydrase
      (anti-CA) autoantibodies. There are many indications that the presence of these
      autoantibodies may provide significant survival benefit for the patients. Western
      blot analysis confirmed strong immunoreactivity of the patients' sera with
      several CA isoforms and the CA I has been selected for our study as a highly
      abundant and widely distributed isoform. The applied analytical approach consists
      of specific fragmentation of CA I protein followed by immunospecific isolation of
      peptides reacting with polyclonal anti-CA I autoantibodies of patients in
      spontaneous remission. We improved the standard epitope mapping schema by
      incorporating the benefits of magnetic carriers and biomagnetic separation
      techniques. Mass spectrometry has been applied for detection and identification
      of epitopes and the acquired results were verified by bioinformatic tools. The
      candidate epitopes of CA I (NVGHS, DGLAV, SSEQL, and SLKPI) are discussed herein
      as potential therapeutic targets. This work highlights the usefulness of the
      epitope mapping technique based on magnetic microspheres for effective and rapid
      determination of immunodominant epitopes of the target protein.

PMID- 20681520
TI  - Iridium Ziegler-type hydrogenation catalysts made from [(1,5-COD)Ir(mu
      O2C8H15)](2) and AlEt3: spectroscopic and kinetic evidence for the Ir(n) species
      present and for nanoparticles as the fastest catalyst.
AB  - Ziegler-type hydrogenation catalysts, those made from a group 8-10 transition
      metal precatalyst and an AlR(3) cocatalyst, are often used for large scale
      industrial polymer hydrogenation; note that Ziegler-type hydrogenation catalysts
      are not the same as Ziegler-Natta polymerization catalysts. A review of prior
      studies of Ziegler-type hydrogenation catalysts (Alley et al. J. Mol. Catal. A:
      Chem. 2010, 315, 1-27) reveals that a approximately 50 year old problem is
      identifying the metal species present before, during, and after Ziegler-type
      hydrogenation catalysis, and which species are the kinetically best, fastest
      catalysts--that is, which species are the true hydrogenation catalysts. Also of
      significant interest is whether what we have termed "Ziegler nanoclusters" are
      present and what their relative catalytic activity is. Reported herein is the
      characterization of an Ir Ziegler-type hydrogenation catalyst, a valuable model
      (vide infra) for the Co-based industrial Ziegler-type hydrogenation catalyst,
      made from the crystallographically characterized [(1,5-COD)Ir(mu
      O(2)C(8)H(15))](2) precatalyst plus AlEt(3). Characterization of this Ir model
      system is accomplished before and after catalysis using a battery of physical
      methods including Z-contrast scanning transmission electron microscopy (STEM),
      high resolution (HR)TEM, and X-ray absorption fine structure (XAFS) spectroscopy.
      Kinetic studies plus Hg(0) poisoning experiments are then employed to probe which
      species are the fastest catalysts. The main findings herein are that (i) a
      combination of the catalyst precursors [(1,5-COD)Ir(mu-O(2)C(8)H(15))](2) and
      AlEt(3) gives catalytically active solutions containing a broad distribution of
      Ir(n) species ranging from monometallic Ir complexes to nanometer scale,
      noncrystalline Ir(n) nanoclusters (up to Ir(approximately 100) by Z-contrast
      STEM) with the estimated mean Ir species being 0.5-0.7 nm, Ir(approximately 4-15)
      clusters considering the similar, but not identical results from the different
      analytical methods; furthermore, (ii) the mean Ir(n) species are practically the
      same regardless of the Al/Ir ratio employed, suggesting that the observed changes
      in catalytic activity at different Al/Ir ratios are primarily the result of
      changes in the form or function of the Al-derived component (and not due to
      significant AlEt(3)-induced changes in initial Ir(n) nuclearity). However (iii),
      during hydrogenation, a shift in the population of Ir species toward roughly 1.0
      1.6 nm, fcc Ir(0)(approximately 40-150), Ziegler nanoclusters occurs with,
      significantly, (iv) a concomitant increase in catalytic activity. Importantly,
      and although catalysis by discrete subnanometer Ir species is not ruled out by
      this study, (v) the increases in activity with increased nanocluster size, plus
      Hg(0) poisoning studies, provide the best evidence to date that the approximately
      1.0-1.6 nm, fcc Ir(0)(approximately 40-150), heterogeneous Ziegler nanoclusters
      are the fastest catalysts in this industrially related catalytic hydrogenation
      system (and in the simplest, Ockham's Razor interpretation of the data). In
      addition, (vi) Ziegler nanoclusters are confirmed to be an unusual, hydrocarbon
      soluble, highly coordinatively unsaturated, Lewis-acid containing, and highly
      catalytically active type of nanocluster for use in other catalytic applications
      and other areas.

PMID- 20681521
TI  - Monitoring gene expression to evaluate oxygen infusion at a gasoline-contaminated
      site.
AB  - Increasingly, molecular biological tools, most notably quantitative polymerase
      chain reaction (qPCR), are being employed to provide a more comprehensive
      assessment of bioremediation of petroleum hydrocarbons and fuel oxygenates. While
      qPCR enumeration of key organisms or catabolic genes can aid in site management
      decisions, evaluation of site activities conducted to stimulate biodegradation
      would ideally include a direct measure of gene expression to infer activity. In
      the current study, reverse-transcriptase (RT) qPCR was used to monitor gene
      expression to evaluate the effectiveness of an oxygen infusion system to promote
      biodegradation of BTEX and MTBE. During system operation, dissolved oxygen (DO)
      levels at the infusion points were greater than 30 mg/L, contaminant
      concentrations decreased, and transcription of two aromatic oxygenase genes and
      Methylibium petroleiphilum PM1-like 16S rRNA copies increased by as many as 5
      orders of magnitude. Moreover, aromatic oxygenase gene transcription and PM1 16s
      rRNA increased at downgradient locations despite low DO levels even during system
      operation. Conversely, target gene expression substantially decreased when the
      system was deactivated. RT-qPCR results also corresponded to increases in benzene
      and MTBE attenuation rates. Overall, monitoring gene expression complemented
      traditional groundwater analyses and conclusively demonstrated that the oxygen
      infusion system promoted BTEX and MTBE biodegradation.

PMID- 20681522
TI  - Cyclophilin A is involved in functional expression of the Na(+)-Ca(2+) exchanger
      NCX1.
AB  - The Na(+)-Ca(2+) exchanger (NCX) is a major Ca(2+) regulating protein. It is
      almost ubiquitously expressed. Cyclophilins (Cyps) make up a class of proteins
      that are involved in protein folding via their peptidyl prolyl cis-trans
      isomerase (PPIase) and chaperone domains. They are also the cellular receptors of
      cyclosporin A (CsA). Binding of CsA to cyclophilins inhibits both PPIase and
      chaperone activities. We have shown that treatment of transfected HEK 293 cells
      expressing the Na(+)-Ca(2+) exchanger NCX1 with CsA results in downregulation of
      surface expression and transport activity, without any reduction in the total
      level of cell NCX1 protein [Kimchi-Sarfaty, C., et al. (2002) J. Biol. Chem. 277
      (4), 2505-2510]. In this work, we show that knockdown of cell CypA using
      targeting siRNA (without any CsA treatment) results in a reduction in the level
      of NCX1 surface expression, a decrease in the level of Na(+)-dependent Ca(2+)
      uptake, and no change in the total amount of cell NCX1 protein in NCX1.5
      transfected HEK 293 cells and nontransfected H9c2 cells that express NCX1.1
      naturally. It also reduced Na(+)-dependent Ca(2+) fluxes measured by changes in
      Fluo-4 AM fluorescence in single NCX1.5-transfected HEK 293 and single H9c2
      cells. Knockdown of CypB had no significant effect on either transport activity,
      surface expression, NCX1 cell protein expression, or Ca(2+) fluxes.
      Overexpression of CypA or its R55A mutant, which exhibits a substantially reduced
      PPIase activity, alleviated the reduction of NCX1 surface expression caused by
      CsA treatment, suggesting that the PPIase domain was probably not mandatory for
      NCX1 functional expression. We suggest that CypA plays a role in the functional
      expression of NCX1 protein.

PMID- 20681523
TI  - Highly diastereoselective Baldwin rearrangement of isoxazolines into cis
      acylaziridines.
AB  - An atom-economical and practical synthesis of cis-N-benzenesulfonamide
      acylaziridines through the Baldwin rearrangement of various N-benzenesulfonamide
      isoxazolines has been reported. A detailed experimental study revealed the
      beneficial effect of microwaves and pointed out the crucial role of the
      temperature in the reaction course. Moderate to good yields and excellent cis
      stereoselectivities were achieved for 13 examples.

PMID- 20681524
TI  - Fold catastrophes and the dependence of free-energy barriers to conformational
      transitions on applied force.
AB  - Applied mechanical force (f) can activate conformational change in molecules by
      reducing the height of a free-energy barrier (DeltaG(b)). In this paper,
      molecular dynamics simulations are carried out with umbrella sampling and self
      consistent histogram methods to determine free-energy profiles for a coarse
      grained model of a protein under an applied force. Applied force is shown to
      cause fold catastrophes, where free-energy minima are destabilized until they
      disappear. It is well-known that a fold catastrophe at force f = B implies the
      scaling DeltaG(b) approximately |B - f|(3/2) in the limit of DeltaG(b) --> 0, but
      it is not clear whether this scaling is accurate for physically relevant barrier
      heights. The simulation results show that the fold catastrophe scaling is in fact
      accurate in the physically relevant regime and that the two-parameter function
      DeltaG(b) = A(B - f)(3/2) is superior to the two-parameter linear function for
      parametrizing changes in free-energy barriers with applied force.

PMID- 20681525
TI  - Temperature-induced reversible dominoes in carbon nanotubes.
AB  - We show by molecular dynamics simulations that there exists a reversible domino
      process in single walled carbon nanotubes (SWCNTs). SWCNTs with one end collapsed
      and the other circular are chosen for demonstration. At a low temperature, the
      collapsed zone spreads over the whole tube, while at a higher temperature, the
      collapsed zone shrinks, and the circular zone extends along the tube. The reason
      for the reversible domino process is that the temperature modifies the stable
      state of the tube. The temperature-induced reversible domino process of SWCNTs
      provides opportunities for the design of nanoscale heat engines, rechargeable
      expelling devices, temperature-sensitive devices, mechanical oscillators, and
      pulse generators, etc.

PMID- 20681526
TI  - Can impact excitation explain efficient carrier multiplication in carbon nanotube
      photodiodes?
AB  - We address recent experiments (Science 2009, 325, 1367) reporting on highly
      efficient multiplication of electron-hole pairs in carbon nanotube photodiodes at
      photon energies near the carrier multiplication threshold (twice the quasi
      particle band gap). This result is surprising in light of recent experimental and
      theoretical work on multiexciton generation in other confined materials, such as
      semiconducting nanocrystals. We propose a detailed mechanism based on carrier
      dynamics and impact excitation resulting in highly efficient multiplication of
      electron-hole pairs. We discuss the important time and energy scales of the
      problem and provide analysis of the role of temperature and the length of the
      diode.

PMID- 20681527
TI  - Dynamic theory of membrane potentials.
AB  - An accurate understanding of the dynamics of membrane potential formation
      underpins modern electrophysiology and much of cell biochemistry. Computer
      simulations using a Nernst-Planck-Poisson (NPP) finite difference method are used
      to model the dynamic evolution of a series of membrane systems in which two
      reservoirs of electrolyte solution are separated by a thin membrane which is
      impermeable to selected species. Two specific examples are considered in detail.
      The first ("type 1") is the case in which the solutions are monophasic but of
      unequal concentration, and the second ("type 2") is the case in which the
      solutions are of equal concentrations but different phase, with a common
      impermeant ion (a bi-ionic membrane). The validity of the Goldman equation for
      membrane potential, as applied to each case, is investigated. The type 1 case is
      shown to reach a steady state, and strong agreement with the Donnan equation for
      potential difference is observed. For the type 2 case, it is shown that the
      potential difference consists of two separable components: a localized, Donnan
      type potential that reaches a pseudosteady state and a dynamically expanding
      diffuse component, with properties similar to those of a liquid junction
      potential, that does not reach a steady state but rather discharges at constant
      potential difference. This is contrary to the classical interpretation of a
      static diffuse layer, due to Planck, Henderson, and Goldman.

PMID- 20681528
TI  - Core-shell nanoarchitectures: a strategy to improve the efficiency of
      luminescence resonance energy transfer.
AB  - The development of core-shell nanoparticles has shown a wide range of new
      applications in the fields of chemistry, bioscience, and materials science
      because of their improved physical and chemical properties over their single
      component counterparts. In the present work, we took the core-shell
      nanoarchitectures as an example to research the luminescence resonance energy
      transfer (LRET) process between a luminescent Tb3+ chelate, N,N,N(1),N(1)-[4'
      phenyl-2,2':6',2'-terpyridine-6,6'-diyl]bis(methylenenitrilo)tetrakis(acetate)
      Tb3+ (PTTA-Tb3+), and an organic dye, 5-carboxytetramethylrhodamine (CTMR). PTTA
      Tb3+ and CTMR were chosen as the donor-acceptor pair of LRET in our model
      construction because of their effective spectral overlapping. The core-shell
      nanoparticles featuring a CTMR-SiO2 core surrounded by a concentric PTTA-Tb3+
      SiO2 shell were prepared using a reverse microemulsion method. These
      nanoparticles are spherical, uniform in size, and highly photostable. The results
      of LRET experiments show that the sensitized emission lifetime of the acceptor in
      the nanoparticles is significantly prolonged (~246 MUs), which is attributed to
      the long emission lifetime of the Tb3+ chelate donor. According to the results of
      the steady-state and time-resolved luminescence spectroscopy, an energy transfer
      efficiency of ~80% and a large Forster distance between the donor and the
      acceptor in the core-shell nanoparticles are calculated, respectively. The new
      core-shell nanoparticles with a high LRET efficiency and long Forster distance
      enable them to be promising optical probes for a variety of possible applications
      such as molecular imaging and multiplex signaling.

PMID- 20681529
TI  - Morphological evolution and ordered quantum structure formation in
      heteroepitaxial core--shell nanowires.
AB  - We have performed three-dimensional dynamic simulations to study strain-driven
      morphological evolution and the formation of quantum structures on
      heteroepitaxial core--shell nanowire surfaces. Our simulations show that
      depending on geometric and material parameters, such as the radius of the wire,
      the thickness of the shell, and the mismatch strain, various surface morphologies
      including smooth core--shell nanowire surfaces, nanoring arrays, nanowire arrays,
      and ordered quantum dot arrays can be obtained by controlling initial surface
      configurations through prepatterning. It is also shown that these quantum
      structures may be trapped in a metastable state and may undergo a series of
      metastable state transitions during subsequent dynamic evolution. Our results
      identify possible pathways for fabrication of ordered quantum structures on the
      epitaxial core--shell nanowire surfaces and provide guidelines for achieving
      smooth core--shell structures.

PMID- 20681530
TI  - Ligand environment of the S2 state of photosystem II: a study of the hyperfine
      interactions of the tetranuclear manganese cluster by 2D 14N HYSCORE
      spectroscopy.
AB  - The solar water-splitting protein complex, photosystem II, catalyzes the light
      driven oxidation of water to dioxygen in Nature. The four-electron oxidation
      reaction of water occurs at the tetranuclear manganese-calcium-oxo catalytic
      cluster that is present in the oxygen-evolving complex of photosystem II. The
      mechanism of light-driven water oxidation has been a subject of intense interest,
      and the oxygen-evolving complex of photosystem II has been studied extensively by
      structural and biochemical methods. While the recent X-ray crystal structures and
      single-crystal EXAFS investigations provide a model for the geometry of the
      tetranuclear manganese-calcium-oxo catalytic cluster, there is limited knowledge
      of the protein environment that surrounds the catalytic cluster. In this study,
      we demonstrate the application of two-dimensional hyperfine sublevel correlation
      spectroscopy to determine the magnetic couplings of the catalytic cluster with
      the (14)N atoms of surrounding amino acid residues in the S(2) state of the
      oxygen-evolving complex of photosystem II. We utilize two-dimensional difference
      spectroscopy to facilitate unambiguous assignments of the spectral features and
      identify at least three separate (14)N atoms that are interacting with the
      catalytic cluster in the S(2) state. The results presented here, for the first
      time, identify previously unknown ligands to the catalytic cluster of photosystem
      II and provide avenues for the assignment of residues by site-directed
      mutagenesis and the refinement of computational and mechanistic models of
      photosystem II.

PMID- 20681531
TI  - Ingested Shiga toxin 2 (Stx2) causes histopathological changes in kidney, spleen,
      and thymus tissues and mortality in mice.
AB  - The Shiga toxin (Stx)-producing bacterial strain, Escherichia coli O157:H7,
      colonizes the distal small intestine and the colon, initiating serious illness,
      including hemolytic-uremic syndrome (HUS), characterized by microangiopathic
      hemolytic anemia, thrombocytopenia, and acute renal failure. Although intravenous
      administration of purified Stx to primates has been able to reproduce the
      features of HUS, it has not been conclusively established as to whether ingestion
      of Stx alone without the bacterium poses a potential health risk. To help answer
      this question, in this study, we fed Shiga toxin 2 (Stx2) directly into the
      stomachs of mice via gavage. Our data show that ingestion of Stx2 at a
      concentration of 50 MUg/mouse induces weight loss and kills the mice at 3-5 days
      post-gavage. Additional studies revealed that the toxin retains activity at low
      pH, that its activity is neutralized by treatment with toxin-specific antibody,
      and that about 1% of the fed toxin is absorbed into the blood circulation.
      Lethality by intraperitoneal (IP) injection of Stx2 occurred at much lower doses
      than by ingestion. Detailed histopathological evaluation of stained tissues by
      light microscopy revealed severe histopathological changes in kidneys, spleen,
      and thymus but not in the pancreas, lymph nodes, heart, lungs, trachea,
      esophagus, stomach, duodenum, jejunum, ileum, cecum, and colon. The pathological
      changes in the kidney appeared similar to those seen in humans with HUS. The
      cited data suggest that (a) most but not all of the toxin is inactivated in the
      digestive tract, (b) part of the oral-ingested toxin is absorbed from the
      digestive tract into the circulation, (c) enough active toxin reaches susceptible
      organs to induce damage, and (d) Stx2 in the absence of toxin-producing bacteria
      can be harmful to mice. The results are clinically relevant for food safety
      because we also found that heat treatments (pasteurization) that destroy bacteria
      did not inactivate the heat-resistant toxin produced and secreted by the
      bacteria.

PMID- 20681532
TI  - Effects of citrus auraptene (7-geranyloxycoumarin) on hepatic lipid metabolism in
      vitro and in vivo.
AB  - Recent reports have shown that citrus auraptene (7-geranyloxycoumarin) possesses
      valuable pharmacological properties, including anticarcinogenic, anti
      inflammatory, antihelicobacter, antigenotoxic, and neuroprotective effects. In
      the present study, we investigated the effect of dietary auraptene on hepatic
      lipid metabolism both in vitro and in vivo. Results suggested that auraptene has
      the ability to normalize lipid abnormalities in HepG2 hepatocytes. After 4 weeks
      of auraptene feeding, abdominal white adipose tissue weight and hepatic
      triglyceride (TG) levels were dose-dependently lowered in Otsuka Long-Evans
      Tokushima fatty (OLETF) rats. The activities of carnitine palmitoyltransferase, a
      key enzyme in mitochondrial fatty acid beta-oxidation, and peroxisomal beta
      oxidation were markedly and dose-dependently enhanced in OLETF rat livers by
      auraptene feeding. Additionally, hepatic expression of acyl-CoA oxidase, the
      initial enzyme of the peroxisomal beta-oxidation system, was significantly and
      dose-dependently enhanced by auraptene administration. These results suggest that
      auraptene administration alleviates obesity and hepatic TG accumulation in part
      through lipolysis enhancement in the livers of obese OLETF rats.

PMID- 20681533
TI  - Crossed molecular beam study on the ground state reaction of atomic boron
      [B((2)P(j))] with hydrogen cyanide [HCN(X(1)sigma(+))].
AB  - The linear boronisocyanide species, [BNC(X(1)Sigma(+))], represents the simplest
      triatomic molecule with three distinct, neighboring main group atoms of the
      second row of the periodic table of the elements: boron, carbon, and nitrogen.
      This makes boronisocyanide a crucial benchmark system to understand the chemical
      bonding and the electronic structure of small molecules, in particular when
      compared to the isoelectronic tricarbon molecule, [CCC(X(1)Sigma(g)(+))].
      However, a clean, directed synthesis of boronisocyanide-a crucial prerequisite to
      study the properties of this molecule-has remained elusive so far. Here, we
      combine crossed molecular beam experiments of ground state boron atoms ((2)P(j))
      with hydrogen cyanide with electronic structure calculations and reveal that the
      boronisocyanide molecule, [BNC(X(1)Sigma(+))], is formed as the exclusive product
      under gas phase single collision conditions. We also show that higher energy
      isomers such as the hitherto unnoticed, ring-strained cyclic BNC(X(3)A')
      structure, which is isoelectronic to the triplet, cyclic tricarbon molecule,
      [C(3)(X(3)A(2)')], do exist as local minima. Our studies present the first
      directed synthesis and observation of gas phase boronisocyanide providing a
      doorway for further fundamental studies on one of the simplest triatomic
      molecules composed solely of group III-V elements.

PMID- 20681534
TI  - NbCl3-catalyzed intermolecular [2+2+2] cycloaddition of alkynes and alpha,omega
      dienes: highly chemo- and regioselective formation of 5-omega-alkenyl-1,4
      substituted-1,3-cyclohexadiene derivatives.
AB  - Intermolecular [2+2+2] cycloaddition of tert-butylacetylene with alpha,omega
      dienes was successfully achieved by NbCl(3)(DME) catalyst to afford 5-omega
      alkenyl-1,4-disubstituted-1,3-cyclohexadienes in excellent yields with high chemo
      and regioselectivity.

PMID- 20681535
TI  - Microwave, Raman, and infrared spectra; adjusted r(0) structural parameters;
      conformational stability; and vibrational assignment of germylcyclohexane.
AB  - The FT-microwave spectrum of germylcyclohexane, c-C(6)H(11)GeH(3), has been
      recorded, and more than 40 transitions for the (70)Ge, (72)Ge, and (74)Ge
      isotopomers (isotopologues) have been assigned for the chair-equatorial
      conformer. The heavy atom adjusted r(0) structural parameters have been
      determined [distances, C(gamma)-C(delta) = 1.533(3) A, C(gamma)-C(beta) =
      1.532(3) A, C(alpha)-C(beta) = 1.540(3) A, C(alpha)-Ge = 1.957(3) A; angles,
      angleC(gamma)C(delta)C(beta) = 111.2(5) degrees , angleGeC(alpha)C(beta) =
      111.1(5) degrees , with the dihedral angle angleC(gamma)C(delta)C(beta)C(alpha) =
      55.6(10) degrees ]. Raman and/or infrared spectra of gas, liquid, and solid
      germylcyclohexane have been recorded. The temperature dependency of the Raman
      spectrum of the conformer pair 712 (equatorial)/683 (axial) cm(-1) gives an
      enthalpy difference of 453 +/- 38 cm(-1) (1.30 +/- 0.11 kcal/mol) with the chair
      equatorial conformer the more stable form. At ambient temperature, the abundance
      of the axial conformer is 11 +/- 1%. Substituent effects on the enthalpy
      difference and structure of monosubstituted cyclohexanes are discussed for a
      number of molecules.

PMID- 20681536
TI  - Theoretical study on the excess electron binding mechanism in the
      [CH(3)NO(2).(H(2)O)(n)](-) (n = 1-6) anion clusters.
AB  - The excess electron binding mechanism of the anionic nitromethane-water clusters
      was theoretically investigated using the potential energy surfaces calculated by
      high-level electronic structure theories. The mechanism was first studied for the
      dipole-bound and valence-bound anionic states of the CH(3)NO(2)(-) monomer with
      the ab initio multireference configuration interaction method to reveal the
      electron transformation process between these anionic states in detail. As a
      result, it was found that both the NO(2) tilting angle and NO distances play an
      essential role in this electron transformation. Following this result, various
      water solvation structures of the valence-bound CH(3)NO(2)(-) anion were
      optimized with up to six water solvents using the second-order Moller-Plesset
      (MP2) method. The calculated results predicted that the vertical detachment
      energy of the valence-bound CH(3)NO(2)(-) anion increases gradually with the
      hydration number, as is consistent with recent experimental observations. We also
      investigated metastable complexes composed of CH(3)NO(2) and (H(2)O)(6)(-) by
      using the MP2 and long-range corrected density functional theory calculations.
      Two types of dipole-bound forms were obtained for the [CH(3)NO(2).(H(2)O)(6)]
      anion complex. In one form the excess electron is internally suspended between
      the two moieties while in the other form two dipolar moieties are cooperatively
      arranged to reinforce the electron-dipole interaction.

PMID- 20681537
TI  - Microhydration of nitromethane anions from both a solute and solvent perspective.
AB  - We present experimental infrared spectroscopic data on mass-selected, hydrated
      nitromethane anion clusters with up to four water ligands. The vibrational bands
      in the OH stretching region encode the solvent structure, while the CH stretching
      bands contain information on the influence of the hydration shell on the solute
      ion. We interpret our findings using density functional theory calculations. The
      first water molecule binds symmetrically to the two oxygen atoms of the nitro
      group but couples to low-frequency vibrational modes that impart a very
      complicated structure on the OH stretching region. Competition between water-ion
      and water-water interaction makes the dihydrate very floppy and precludes
      unambiguous structural assignment. The tri- and tetrahydrate spectra can be
      interpreted on the basis of H-bonded ring structures. The excess electron is
      polarized by hydration, which can clearly be seen by shifting CH stretching
      frequencies.

PMID- 20681538
TI  - Discovery of pyrrole-indoline-2-ones as Aurora kinase inhibitors with a different
      inhibition profile.
AB  - A series of pyrrole-indolin-2-ones were synthesized, and their inhibition profile
      for Aurora kinases was studied. The potent compound 33 with phenylsulfonamido at
      the C-5 position and a carboxyethyl group at the C-3' position selectively
      inhibited Aurora A over Aurora B with IC50 values of 12 and 156 nM, respectively.
      Replacement of the carboxyl group with an amino group led to compound 47, which
      retained the activity for Aurora B and lost activity for Aurora A (IC50=2.19
      microM). Computation modeling was used to address the different inhibition
      profiles of 33 and 47. Compounds 47 and 36 (the ethyl ester analogue of 33)
      inhibited the proliferation of HCT-116 and HT-29 cells and suppressed levels of
      the phosphorylated substrates of Aurora A and Aurora B in the Western blots.

PMID- 20681539
TI  - Reverse engineering truncations of an antimicrobial peptide dimer to identify the
      origins of potency and broad spectrum of action.
AB  - Antimicrobial peptides hold promise against antibiotic resistant pathogens. Here,
      to find the physicochemical origins of potency and broad spectrum antimicrobial
      action, we report the structure-activity relationships of synthetic intermediates
      (peptides A-D) of a potent lysine branched dimeric antibacterial peptide DeltaFd.
      Our studies show that a tetracationic character in a weak helical fold (peptide
      C) elicits potent but narrow spectrum antimicrobial activity [Minimum inhibitory
      concentrations (MICs) E. coli 10 microM, S. aureus>100 microM]. In contrast, a
      hexacationic character in a strong, amphipathic helix (DeltaFd) confers potent
      and broad spectrum action [MICs E. coli 2.5 microM, S. aureus 5 microM]. While
      DeltaFd caused rapid and potent permeabilization of the E. coli membranes, the
      less helical intermediates (peptides A-D) showed slow and weak to no responses.
      Two seminal findings that may aid future drug design are (a) at identical
      helicity, increasing charge enhanced outer membrane permeabilization, and (b) at
      identical charge, increasing helicity stimulated rate of outer membrane
      permeabilization and kill kinetics besides enhancing potency leading to broad
      spectrum action.

PMID- 20681540
TI  - Optimal pi-stacking interaction energies in parallel-displaced aryl/aryl dimers
      are predicted by the dimer heavy atom count.
AB  - It is generally accepted that large basis sets are required for the accurate
      calculation of interaction energies for weakly bound aryl dimers, but it has
      recently been reported that MP2(full)/6-31G* energies, although inaccurate in
      absolute terms, are well-correlated with estimated CCSD(T)/CBS results. It is now
      shown that this correlation holds for MP2/aug-cc-pVDZ and SCS-MP2/aug-cc-pVDZ
      values. Linear regression of published CCSD(T)/CBS results with MP2 or SCS-MP2
      results has been used to correct systematic errors observed with both MP2
      theories, and these corrections are applied to 27 parallel-displaced aromatic
      dimers of interest in medicinal chemistry. The optimal computed interaction
      energies are found to be strongly correlated with the heavy atom counts of the
      aryl/aryl dimers. This relationship between heavy atom count and interaction
      energy also applies to a series of 12 aryl/non-aryl dimers such that a single
      linear regression equation accounts for all of the dimers studied.

PMID- 20681541
TI  - Nitrate in United kingdom rivers: policy and its outcomes since 1970.
AB  - Modern conventional farming provides Western Europe and North America with
      reliable, high quality, and relatively cheap supplies of food and fiber,
      increasingly viewed as a potential source of fuel. One of the costs is continued
      widespread pollution of rivers and groundwater-predominantly by nutrients. In
      1970, in both the United States and UK, farming was focused on maximizing yield
      and management practices were rapidly modernizing. Little attention was paid to
      the external impacts of farming. In 2010, diffuse pollution from agriculture is
      being seriously addressed by both voluntary and statutory means in an attempt to
      balance environmental costs with the continued benefits of agricultural
      production. In this paper we consider long-term changes in the concentration and
      flux of nitrate in five rural UK rivers to demonstrate the impact of agricultural
      intensification and subsequent policies to reduce diffuse pollution on river
      water quality between 1970 and 2010.

PMID- 20681542
TI  - Gas phase reaction of nitric acid with hydroxyl radical without and with water. A
      theoretical investigation.
AB  - The gas phase reaction between nitric acid and hydroxyl radical, without and with
      a single water molecule, has been investigated theoretically using the DFT-B3LYP,
      MP2, QCISD, and CCSD(T) theoretical approaches with the 6-311+G(2df,2p) and aug
      cc-pVTZ basis sets. The reaction without water begins with the formation of a
      prereactive hydrogen-bonded complex and has several elementary reactions
      processes. They include proton coupled electron transfer, hydrogen atom transfer,
      and proton transfer mechanisms, and our kinetic study shows a quite good
      agreement of the behavior of the rate constant with respect to the temperature
      and to the pressure with the experimental results from the literature. The
      addition of a single water molecule results in a much more complex potential
      energy surface although the different elementary reactions found have the same
      electronic features that the naked reaction. Two transition states are stabilized
      by the effect of a hydrogen bond interaction originated by the water molecule,
      and in the prereactive hydrogen bond region there is a geometrical rearrangement
      necessary to prepare the HO and HNO(3) moieties to react to each other. This step
      contributes the reaction to be slower than the reaction without water and
      explains the experimental finding, pointing out that there is no dependence for
      the HNO(3) + HO reaction on water vapor.

PMID- 20681543
TI  - A new class of antitumor trans-amine-amidine-Pt(II) cationic complexes: influence
      of chemical structure and solvent on in vitro and in vivo tumor cell
      proliferation.
AB  - The reactions of cyclopropylamine, cyclopentylamine, and cyclohexylamine with
      trans-[PtCl2(NCMe)2] afforded the bis-cationic complexes trans-[Pt(amine)2(Z
      amidine)2]2+[Cl-]2, 1-3. The solution behavior and biological activity have been
      studied in different solvents (DMSO, water, polyethylene glycol (PEG 400), and
      polyethylene glycol dimethyl ether (PEG-DME 500)). The biological activity was
      strongly influenced by the cycloaliphatic amine ring size, with trans
      [Pt(NH2CH(CH2)4CH2)2{N(H) horizontal lineC(CH3)N(H)CH(CH2)4CH2}2]2+[Cl-]2 (3)
      being the most active compound. Complex 3 overcame both cisplatin and MDR
      resistance, inducing cancer cell death through p53-mediated apoptosis. Alkaline
      single-cell gel electrophoresis experiments indicated direct DNA damage,
      reasonably attributable to DNA adducts of trans-[PtCl(amine)(Z-amidine)2][Cl]
      species, which can evolve to produce disruptive and nonrepairable lesions on DNA,
      thus leading to the drug-induced programmed cancer cell death. Preliminary in
      vivo antitumor studies on C57BL mice bearing Lewis lung carcinoma highlighted
      that complex 3 promoted a significant and dose-dependent tumor growth inhibition
      without adverse side effects.

PMID- 20681544
TI  - Butein up-regulates the expression of the pi class of glutathione S-transferase
      in rat primary hepatocytes through the ERK/AP-1 pathway.
AB  - Induction of phase II enzymes is an important mechanism of chemoprevention. Here
      we compared the effects of chalcones on the expression of the pi class of
      glutathione S-transferase (GSTP) in rat primary hepatocytes. Hepatocytes were
      treated with 10 or 25 MUM of phloretin or butein for 24 h. Both butein and
      phloretin dose-dependently increased GSTP protein expression, and the induction
      potency of butein was stronger than that of phloretin. The increase in GSTP mRNA
      in cells treated with 25 MUM of phloretin and butein was 107% and 211%,
      respectively (P < 0.05). Butein increased GST enzyme activity by 27% compared
      with that in the control cells (P < 0.05). In contrast, phloretin had no
      significant effect on GST enzyme activity. The pTA-luciferase reporter construct
      with the rat -2.7 kb GSTP promoter region was transiently transfected into Clone
      9 liver cells, and the luciferase activity in butein-treated cells was 1.1-fold
      higher than that in control cells (P < 0.05). GSTP enhancer 1 (GPE1) deletion
      abolished the induction of reporter activity by butein. The phosphorylation of
      extracellular signal-regulated kinase (ERK), but not of c-Jun NH2-terminal kinase
      (JNK) and p38, was stimulated in the presence of butein. Pretreatment with
      PD98059, an ERK inhibitor, alleviated the increase in activator protein-1 (AP-1)
      DNA binding activity and also the activation of GSTP protein expression by
      butein. Moreover, c-Jun is likely to bind to the GPE1. Silencing of ERK2 by siRNA
      gene knockdown reduced the butein-induced expression of GSTP. In conclusion, the
      increased GSTP expression by butein is likely related to the ERK-AP-1 pathway.

PMID- 20681545
TI  - A cooperative Escherichia coli aspartate transcarbamoylase without regulatory
      subunits .
AB  - Here we report the isolation, kinetic characterization, and X-ray structure
      determination of a cooperative Escherichia coli aspartate transcarbamoylase
      (ATCase) without regulatory subunits. The native ATCase holoenzyme consists of
      six catalytic chains organized as two trimers bridged noncovalently by six
      regulatory chains organized as three dimers, c(6)r(6). Dissociation of the native
      holoenzyme produces catalytically active trimers, c(3), and nucleotide-binding
      regulatory dimers, r(2). By introducing specific disulfide bonds linking the
      catalytic chains from the upper trimer site specifically to their corresponding
      chains in the lower trimer prior to dissociation, a new catalytic unit, c(6), was
      isolated consisting of two catalytic trimers linked by disulfide bonds. Not only
      does the c(6) species display enhanced enzymatic activity compared to the wild
      type enzyme, but the disulfide bonds also impart homotropic cooperativity, never
      observed in the wild-type c(3). The c(6) ATCase was crystallized in the presence
      of phosphate and its X-ray structure determined to 2.10 A resolution. The
      structure of c(6) ATCase liganded with phosphate exists in a nearly identical
      conformation as other R-state structures with similar values calculated for the
      vertical separation and planar angles. The disulfide bonds linking upper and
      lower catalytic trimers predispose the active site into a more active
      conformation by locking the 240s loop into the position characteristic of the
      high-affinity R state. Furthermore, the elimination of the structural constraints
      imposed by the regulatory subunits within the holoenzyme provides increased
      flexibility to the c(6) enzyme, enhancing its activity over the wild-type
      holoenzyme (c(6)r(6)) and c(3). The covalent linkage between upper and lower
      catalytic trimers restores homotropic cooperativity so that a binding event at
      one or so active sites stimulates binding at the other sites. Reduction of the
      disulfide bonds in the c(6) ATCase results in c(3) catalytic subunits that
      display kinetic parameters similar to those of wild-type c(3). This is the first
      report of an active c(6) catalytic unit that displays enhanced activity and
      homotropic cooperativity.

PMID- 20681547
TI  - Physico-chemical characteristics of media-milled corn starch.
AB  - Nano/submicrometer scale corn starch particles have been prepared by using media
      milling. Molecular weight and pasting properties of milled starch were determined
      by HPSEC-MALLS-RI and an oscillatory rheometer, respectively. After 30-min of
      milling, the number-average diameter of the starch particle was reduced from 9.61
      to 0.26 MUm. Particle size was further reduced by extended milling. Microscopic
      observation confirmed the presence of particles smaller than 100 nm. As starch
      granules were being disintegrated, the mechanical energy imparted by media
      milling resulted in 43.7% of starch damage and 55% degree of gelatinization
      during the initial 30 min. In the meanwhile, the weight average molecular weight
      was reduced from 9.98 to 7.63 * 10(6) g/mol. The pasting properties were
      significantly altered by milling, which resulted in lower onset and peak
      temperature, and reduction in breakdown and set back. The importance of molecular
      weight on the physicochemical properties of milled starch was discussed.

PMID- 20681546
TI  - Oxidation reactions performed by soluble methane monooxygenase hydroxylase
      intermediates H(peroxo) and Q proceed by distinct mechanisms.
AB  - Soluble methane monooxygenase is a bacterial enzyme that converts methane to
      methanol at a carboxylate-bridged diiron center with exquisite control. Because
      the oxidizing power required for this transformation is demanding, it is not
      surprising that the enzyme is also capable of hydroxylating and epoxidizing a
      broad range of hydrocarbon substrates in addition to methane. In this work we
      took advantage of this promiscuity of the enzyme to gain insight into the
      mechanisms of action of H(peroxo) and Q, two oxidants that are generated
      sequentially during the reaction of reduced protein with O(2). Using double
      mixing stopped-flow spectroscopy, we investigated the reactions of the two
      intermediate species with a panel of substrates of varying C-H bond strength.
      Three classes of substrates were identified according to the rate-determining
      step in the reaction. We show for the first time that an inverse trend exists
      between the rate constant of reaction with H(peroxo) and the C-H bond strength of
      the hydrocarbon examined for those substrates in which C-H bond activation is
      rate-determining. Deuterium kinetic isotope effects revealed that reactions
      performed by Q, but probably not H(peroxo), involve extensive quantum mechanical
      tunneling. This difference sheds light on the observation that H(peroxo) is not a
      sufficiently potent oxidant to hydroxylate methane, whereas Q can perform this
      reaction in a facile manner. In addition, the reaction of H(peroxo) with
      acetonitrile appears to proceed by a distinct mechanism in which a cyanomethide
      anionic intermediate is generated, bolstering the argument that H(peroxo) is an
      electrophilic oxidant that operates via two-electron transfer chemistry.

PMID- 20681548
TI  - Lithium insertion in silicon nanowires: an ab initio study.
AB  - The ultrahigh specific lithium ion storage capacity of Si nanowires (SiNWs) has
      been demonstrated recently and has opened up exciting opportunities for energy
      storage. However, a systematic theoretical study on lithium insertion in SiNWs
      remains a challenge, and as a result, understanding of the fundamental
      interaction and microscopic dynamics during lithium insertion is still lacking.
      This paper focuses on the study of single Li atom insertion into SiNWs with
      different sizes and axis orientations by using full ab initio calculations. We
      show that the binding energy of interstitial Li increases as the SiNW diameter
      grows. The binding energies at different insertion sites, which can be classified
      as surface, intermediate, and core sites, are quite different. We find that
      surface sites are energetically the most favorable insertion positions and that
      intermediate sites are the most unfavorable insertion positions. Compared with
      the other growth directions, the [110] SiNWs with different diameters always
      present the highest binding energies on various insertion locations, which
      indicates that [110] SiNWs are more favorable by Li doping. Furthermore, we study
      Li diffusion inside SiNWs. The results show that the Li surface diffusion has a
      much higher chance to occur than the surface to core diffusion, which is
      consistent with the experimental observation that the Li insertion in SiNWs is
      layer by layer from surface to inner region. After overcoming a large barrier
      crossing surface-to-intermediate region, the diffusion toward center has a higher
      possibility to occur than the inverse process.

PMID- 20681550
TI  - Nanophase evolution at semiconductor/electrolyte interface in situ probed by time
      resolved high-energy synchrotron X-ray diffraction.
AB  - Real-time evolution of nanoparticles grown at the semiconductor/electrolyte
      interface formed between a single crystalline n-type GaAs wafer and an aqueous
      solution of AgNO(3) has been studied by using high-energy synchrotron X-ray
      diffraction. The results reveal the distinct nucleation and growth steps involved
      in the growth of anisotropic Ag nanoplates on the surface of the GaAs wafer. For
      the first time, a quick transit stage is observed to be responsible for the
      structural transformation of the nuclei to form structurally stable seeds that
      are critical for guiding their anisotropic growth into nanoplates. Reaction
      between a GaAs wafer and AgNO(3) solution at room temperature primarily produces
      Ag nanoplates on the surface of the GaAs wafer in the dark and at room
      temperature. In contrast, X-ray irradiation can induce charge separation in the
      GaAs wafer to drive the growth of nanoparticles made of silver oxy salt
      (Ag(7)NO(11)) and silver arsenate (Ag(3)AsO(4)) at the semiconductor/electrolyte
      interface if the GaAs wafer is illuminated by the X-ray and reaction time is long
      enough.

PMID- 20681551
TI  - Stability of apigeninidin and its methoxylated derivatives in the presence of
      sulfites.
AB  - 3-Deoxyanthocyanin pigments are more stable than anthocyanins and show promising
      bioactive properties. However, little is known about their stability in the
      presence of food additives such as sulfites. This work investigates the stability
      of apigeninidin and its derivatives in the presence of sulfites. Pigment
      (apigeninidin, 5-mono-, and 5,7-dimethoxyapigeninidin) stability at pH 1.8, 3.0,
      and 5.0, in the presence of sodium metabisulfite (molar ratio ~ 1:40,
      pigment/SO2) was monitored over 21 days at room temperature. The structure of
      sulfite complexation products was monitored using HPLC-MS and NMR spectroscopy.
      All pigments were significantly bleached within 30 min in the presence of
      sulfites; the bleaching effect was more severe at pH 5.0 and 3.0 compared to pH
      1.8. Apigeninidin was more resistant to bleaching than its methoxylated
      derivatives. However, all pigments regained some or all of the bleached color
      within 14-21 days at pH 3.0 and 1.8 in the presence of sulfites, indicating
      equilibrium favored flavylium cation at these pH values. Formation of colorless
      sulfonates via bisulfite ion addition at C-4 was responsible for the bleaching
      effect. Both structure and pH significantly affected stability of 3
      deoxyanthocyanidins in the presence of sulfites. The pigments may have potential
      applications in low pH systems containing sulfites.

PMID- 20681552
TI  - Kinetic resolution of racemic alpha-arylalkanoic acids with achiral alcohols via
      the asymmetric esterification using carboxylic anhydrides and acyl-transfer
      catalysts.
AB  - A variety of optically active carboxylic esters are produced by the kinetic
      resolution of racemic alpha-substituted carboxylic acids using achiral alcohols,
      aromatic or aliphatic carboxylic anhydrides, and chiral acyl-transfer catalysts.
      The combination of 4-methoxybenzoic anhydride (PMBA) or pivalic anhydride with
      the modified benzotetramisole-type catalyst ((S)-beta-Np-BTM) is the most
      effective for promotion of the enantioselective coupling reaction between racemic
      carboxylic acids and a novel nucleophile, bis(alpha-naphthyl)methanol, to give
      the corresponding esters with high ee's. This protocol was successfully applied
      to the production of nonracemic nonsteroidal anti-inflammatory drugs from racemic
      compounds utilizing the transacylation process to generate the mixed anhydrides
      from the acid components with the suitable carboxylic anhydrides.

PMID- 20681553
TI  - Computational thermochemistry of six ureas, imidazolidin-2-one, N,N'
      trimethyleneurea, benzimidazolinone, parabanic acid, barbital (5,5'
      diethylbarbituric acid), and 3,4,4'-trichlorocarbanilide, with an extension to
      related compounds.
AB  - A computational study of the structural and thermochemical properties of N-phenyl
      (open) and N-alkyl (cyclic) ureas, through the use of M05-2X and B3LYP density
      functional theory calculations has been carried out. The consistency of the
      literature experimental results has been confirmed, and using mainly isodesmic
      reactions, the unknown Delta(f)H(0)(g) of the other urea derivatives were
      estimated. The experimental results together with the theoretical information
      have permitted the study of the effect of phenyl, p- and m-chlorophenyl, alkyl,
      and carbonyl substitutions on the thermodynamical stability of urea and its
      cyclic derivatives. The peculiar behavior of the N-tert-butyl substituent in
      cyclic ureas has been related to geometric deformations.

PMID- 20681554
TI  - Effect of protein content and denaturation on the extractability and stability of
      isoflavones in different soy systems.
AB  - The effect of protein on the thermal stability of isoflavones and the efficiency
      of their extraction from various soy matrixes was investigated. Isoflavones were
      extracted from soymilk, soybean. and soy protein isolate, varying in protein
      content and/or denaturation state, following nonenzyme-assisted solvent
      extraction or enzyme-assisted extraction. Selected samples were subjected to
      thermal treatment prior to and posthydrolysis of the protein. The extraction
      efficiency was a function of the enzyme used, sample to solvent ratio, protein
      content, and protein denaturation state. Proteolysis and reducing the sample to
      solvent ratio enhanced the isoflavone extractability, especially in samples with
      denatured protein. Results demonstrated clearly that the solvent extraction
      techniques currently used considerably underestimate isoflavone content in
      complex soy systems with high protein content. The stability of isoflavones was
      reduced upon protein hydrolysis, indicating that the protein moiety may have a
      protective effect against the thermal degradation of isoflavones.

PMID- 20681556
TI  - Effects of structural fluctuations on two-photon absorption activity of
      interacting dipolar chromophores.
AB  - One- and two-photon absorption properties of organic chromophores consisting of
      interacting dipolar branches have been studied using density functional response
      theory in combination with molecular dynamics simulation. Effects of dipole
      interaction on optical absorptions have been examined. The importance of solvent
      effects on optical properties of charge-transfer states is explored by means of
      polarizable continuum model. It is found that for the interacting dipolar
      molecule with flexible conformations in solutions, the structural fluctuations
      can result in new spectral features or significant broadening of one-photon
      absorption spectrum. Our study highlights again the usefulness of the combined
      quantum chemical and molecular dynamics approach for modeling two-photon
      absorption materials in solutions.

PMID- 20681555
TI  - Nanoparticles based on PLGA:poloxamer blends for the delivery of proangiogenic
      growth factors.
AB  - New blood vessel formation is a critical requirement for treating many vascular
      and ischemia related diseases, as well as for many tissue engineering
      applications. Angiogenesis and vasculogenesis, in fact, represent crucial
      processes for the functional regeneration of complex tissues through tissue
      engineering strategies. Several growth factors (GFs) and signaling molecules
      involved in blood vessels formation have been identified, but their application
      to the clinical setting is still strongly limited by their extremely short half
      life in the body. To overcome these limitations, we have developed a new
      injectable controlled release device based on polymeric nanoparticles for the
      delivery of two natural proangiogenic GFs: platelet derived growth factor (PDGF
      BB) and fibroblast growth factor (FGF-2). The nanoparticle system was prepared by
      a modified solvent diffusion technique, encapsulating the GF both in presence and
      in the absence of two stabilizing agents: bovine serum albumin (BSA) and heparin
      sodium salt (Hp). The developed nanocarriers were characterized for morphology,
      size, encapsulation efficiency, release kinetics in vitro and GF activity in cell
      cultures. The results have indicated that the coencapsulation of stabilizing
      agents can preserve the GF active structure and, in addition, increase their
      encapsulation efficiency into nanoparticles. Through this optimization process,
      we were able to raise the encapsulation efficiency of FGF-2 to 63%, and that of
      PDGF-BB to 87%. These PLGA:poloxamer blend nanoparticles loaded with GFs were
      able to release PDGF-BB and FGF-2 in a sustained fashion for more than a month.
      This work also confirms other positive features of PLGA:poloxamer nanoparticles.
      Namely, they are able to maintain their stability in simulated biological medium,
      and they are also nontoxic to cell culture models. Incubation of nanoparticles
      loaded with FGF-2 or PDGF-BB with endothelial cell culture models has confirmed
      that GFs are released in a bioactive form. Altogether, these results underline
      the interest of PLGA:poloxamer nanoparticles for the controlled delivery of GFs
      and substantiate their potential for the treatment of ischemic diseases and for
      tissue engineering applications.

PMID- 20681557
TI  - Effects of DHLA-capped CdSe/ZnS quantum dots on the fibrillation of human serum
      albumin.
AB  - Nanoparticles (NPs) are extremely small in size and possess very large surface
      areas, which gives them unique properties and applications distinct from those of
      bulk systems. When exposed to biological fluid, these NPs may become coated with
      proteins and other biomolecules given their dynamic nature. Hence, there is a
      significant possibility of an enhanced rate of protein fibrillation by utilizing
      the NPs as nucleation centers and, thus, promoting fibril formation. Protein
      fibrillation is closely associated with many fatal human diseases, including
      neurodegenerative diseases and a variety of systemic amyloidoses. This topic of
      protein-NP interaction brings about many key issues and concerns, especially with
      respect to the potential risks to human health and the environment. Herein, we
      demonstrate the effects of specific NPs, semiconductor quantum dots (QDs), in the
      process of protein fibril formation from samples of human serum albumin (HSA).
      The protein-NP systems are analyzed by time-lapse Thioflavin T spectroscopy,
      Congo red binding assays, circular dichroism (CD), protein fluorescence
      spectroscopy, and transmission electron microscopy (TEM). Our experimental
      results illustrate that an increased rate of fibrillation occurs following a
      thermally activated mechanism in conjunction with the addition of NPs into the
      protein system. These results give rise to the understanding and possibility of
      controlling biological self-assembly processes for use in nanobiotechnology and
      nanomedicine.

PMID- 20681558
TI  - Diffusive mixing of polymers investigated by Raman microspectroscopy and
      microrheology.
AB  - Diffusive mixing in a model polymer blend of limited miscibility (i.e., the pair
      polydimethylsiloxane/polyisobutene) is investigated. The diffusion process is
      followed in the actual droplet-based microstructure of the polymer blend, as
      opposed to the ideal planar geometry used in previous studies (Brochard et al.
      Macromolecules 1983, 16, 1638; Composto et al. Nature 1987, 328, 234). In our
      experiments we combine Raman microspectroscopy and video particle-tracking
      microrheology. The first technique allows us to monitor local concentration of
      the two polymers with high spatial resolution both inside and outside a
      micrometer-size droplet of the dispersed phase. In addition, microrheology
      enables to follow how the local viscosity inside the droplet changes during the
      diffusion. The polymer viscosity inside the droplet is determined by video
      tracking the Brownian motion of a polystyrene bead microinjected into the
      droplet. The microspectroscopic and microrheological data are combined to
      estimate the concentration dependence of the monomer friction factor of the two
      species, which is a key parameter to calculate the interdiffusion coefficient D.
      Numerical calculations based on such concentration-dependent interdiffusion
      coefficient D and several alternative models of the polymer diffusion are
      compared to the experimental concentration profiles. A satisfactory agreement is
      found for the so-called "slow theory" (Brochard et al.). A phenomenological model
      improving the agreement of the model with the experimental data is also
      presented.

PMID- 20681559
TI  - Identification of biological tissues by rapid evaporative ionization mass
      spectrometry.
AB  - The newly developed rapid evaporative ionization mass spectrometry (REIMS)
      provides the possibility of in vivo, in situ mass spectrometric tissue analysis.
      The experimental setup for REIMS is characterized in detail for the first time,
      and the description and testing of an equipment capable of in vivo analysis is
      presented. The spectra obtained by various standard surgical equipments were
      compared and found highly specific to the histological type of the tissues. The
      tissue analysis is based on their different phospholipid distribution; the
      identification algorithm uses a combination of principal component analysis (PCA)
      and linear discriminant analysis (LDA). The characterized method was proven to be
      sensitive for any perturbation such as age or diet in rats, but it was still
      perfectly suitable for tissue identification. Tissue identification accuracy
      higher than 97% was achieved with the PCA/LDA algorithm using a spectral database
      collected from various tissue species. In vivo, ex vivo, and post mortem REIMS
      studies were performed, and the method was found to be applicable for
      histological tissue analysis during surgical interventions, endoscopy, or after
      surgery in pathology.

PMID- 20681560
TI  - Multiplexed NMR: an automated CapNMR dual-sample probe.
AB  - A new generation of microscale, nuclear magnetic resonance (CapNMR) probe
      technology employs two independent detection elements to accommodate two samples
      simultaneously. Each detection element in the dual-sample CapNMR probe (DSP)
      delivers the same spectral resolution and S/N as in a CapNMR probe configured to
      accommodate one sample at a time. A high degree of electrical isolation allows
      the DSP to be used in a variety of data acquisition modes. Both samples are
      shimmed simultaneously to achieve high spectral resolution for simultaneous data
      acquisition, or alternatively, a flowcell-specific shim set is readily called via
      spectrometer subroutines to enable acquisition from one sample while the other is
      being loaded. An automation system accommodates loading of two samples via dual
      injection ports on an autosampler and two completely independent flowpaths
      leading to dedicated flowcells in the DSP probe.

PMID- 20681561
TI  - Microfabrication of carbon structures by pattern miniaturization in resorcinol
      formaldehyde gel.
AB  - A simple and novel method to fabricate and miniaturize surface and subsurface
      microstructures and micropatterns in glassy carbon is proposed and demonstrated.
      An aqueous resorcinol-formaldehyde (RF) sol is employed for micromolding of the
      master pattern to be replicated, followed by controlled drying and pyrolysis of
      the gel to reproduce an isotropically shrunk replica in carbon. The miniaturized
      version of the master pattern thus replicated in carbon is about 1 order of
      magnitude smaller than original master by repeating three times the above cycle
      of molding and drying. The microfabrication method proposed will greatly enhance
      the toolbox for a facile fabrication of a variety of carbon-MEMS and C
      microfluidic devices.

PMID- 20681562
TI  - Detection and characterization of cholesterol-oxidized products using HPLC
      coupled to dopant assisted atmospheric pressure photoionization tandem mass
      spectrometry.
AB  - Oxidation of cholesterol (Ch) by a variety of reactive oxygen species gives rise
      mainly to hydroperoxides and aldehydes. Despite the growing interest in Ch
      oxidized products, the detection and characterization of these products is still
      a matter of concern. In this work, the main Ch-oxidized products, namely, 3beta
      hydroxycholest-5-ene-7alpha-hydroperoxide (7alpha-OOH), 3beta-5alpha-cholest-6
      ene-5-hydroperoxide (5alpha-OOH), 3beta-hydroxycholest-4-ene-6alpha-hydroperoxide
      (6alpha-OOH), 3beta-hydroxycholest-4-ene-6beta-hydroperoxide (6beta-OOH), and
      3beta-hydroxy-5beta-hydroxy-B-norcholestane-6beta-carboxaldehyde (ChAld), were
      detected in the same analysis using high-performance liquid chromatography (HPLC)
      coupled to dopant assisted atmospheric pressure photoionization tandem mass
      spectrometry. The use of selected reaction monitoring mode (SRM) allowed a
      sensitive detection of each oxidized product, while the enhanced product ion mode
      (EPI) helped to improve the confidence of the analyses. Isotopic labeling
      experiments enabled one to elucidate mechanistic features during fragmentation
      processes. The characteristic fragmentation pattern of Ch-oxidized products is
      the consecutive loss of H(2)O molecules, yielding cationic fragments at m/z 401,
      383, and 365. Homolytic scissions of the peroxide bond are also seen. With (18)O
      labeling approach, it was possible to establish a fragmentation order for each
      isomer. The SRM transitions ratio along with EPI and (18)O-labeled experiments
      give detailed information about differences for water elimination, allowing a
      proper discrimination between the isomers. This is of special interest
      considering the emerging role of Ch-oxidized products in the development of
      diseases.

PMID- 20681564
TI  - Reactions of H2S with AgCl within a porous coordination network.
AB  - A silver(I) sulfide species is now imbedded in a porous coordination network.
      Such a composite system builds on the molecule tetrakis(methylthio)-1,4
      benzenedicarboxate that holds out the hard carboxylate to europium(III) to form a
      host net, while taking on AgCl using its soft sulfur side arms. AgCl is then
      treated with H(2)S to form the dark-colored Ag(2)S species, while leaving the
      hard host net intact and upstanding. This hard-soft duality serves to conjoin the
      rich electronic flavors of metal chalcogenides and the flexible textures of
      coordination nets.

PMID- 20681563
TI  - Visual detection of single-nucleotide polymorphism with hairpin oligonucleotide
      functionalized gold nanoparticles.
AB  - We report a simple, fast, and sensitive approach for visual detection of single
      nucleotide polymorphism (SNP) based on hairpin oligonucleotide-functionalized
      gold nanoparticle (HO-Au-NP) and lateral flow strip biosensor (LFSB). The results
      presented here expand on prior work ( Mao , X. , Xu , H. , Zeng , Q. , Zeng , L.
      , and Liu , G. Chem. Commun. 2009 , 3065-3067 .) by providing new approach to
      prepare HO-Au-NP conjugates with a deoxyadenosine triphosphate (dATP) blocker,
      which shortens the preparation time of the conjugates from 50 to 8 h and lowers
      the detection limit 500 times. A hairpin oligonucleotide modified with a thiol at
      the 5'-end and a biotin at the 3'-end was conjugated with Au-NP through a self
      assembling process. Following a blocking step with dATP, the hairpin structure of
      HO and dATP embed the biotin groups, and make the biotin groups in close
      proximity to the Au-NP surface, leading to the biotins being "inactive". The
      strategy of detecting SNP depends on the unique molecular recognition properties
      of HO to the perfect-matched DNA and single-base-mismatched DNA to generate
      different quantities of "active" biotin groups on the Au-NP surface. After
      hybridization reactions, the Au-NPs associated with the activated biotins are
      captured on the test zone of LFSB via the specific reaction between the activated
      biotin and preimmobilized streptavidin. Accumulation of Au-NPs produces the
      characteristic red bands, enabling visual detection of SNP. The preparations of
      HO-Au-NP conjugates with dATP and the parameters of assay were optimized
      systematically, and the abilities of detecting SNP were examined in details. The
      current approach is capable of discriminating as low as 10 pM of perfect-matched
      DNA and single-base-mismatched DNA within 25 min without instrumentation.
      Moreover, the approach provides a lower background and higher selectivity
      compared to the current molecular beacon-based SNP detection. The protocol should
      facilitate the simple, fast, and cost-effective screening of important SNPs and
      could readily find wide applications in molecular diagnosis laboratories and in
      point-of-care testing (field testing).

PMID- 20681565
TI  - Semivolatile endocrine-disrupting compounds in paired indoor and outdoor air in
      two northern California communities.
AB  - Interest in the health effects of potential endocrine-disrupting compounds (EDCs)
      that are high production volume chemicals used in consumer products has made
      exposure assessment and source identification a priority. We collected paired
      indoor and outdoor air samples in 40 nonsmoking homes in urban, industrial
      Richmond, CA, and 10 in rural Bolinas, CA. Samples were analyzed by GC-MS for 104
      analytes, including phthalates (11), alkylphenols (3), parabens (3),
      polybrominated diphenyl ether (PBDE) flame retardants (3), polychlorinated
      biphenyls (PCBs) (3), polycyclic aromatic hydrocarbons (PAHs) (24), pesticides
      (38), and phenolic compounds (19). We detected 39 analytes in outdoor air and 63
      in indoor air. For many of the phenolic compounds, alkylphenols, phthalates, and
      PBDEs, these represent some of the first outdoor measures and the first analysis
      of the relative importance of indoor and outdoor sources in paired samples. Data
      demonstrate higher indoor concentrations for 32 analytes, suggesting primarily
      indoor sources, as compared with only 2 that were higher outdoors. Outdoor air
      concentrations were higher in Richmond than Bolinas for 3 phthalates, 10 PAHs,
      and o-phenylphenol, while indoor air levels were more similar between
      communities, except that differences observed outdoors were also seen indoors.
      Indoor concentrations of the most ubiquitous chemicals were generally correlated
      with each other (4-t-butylphenol, o-phenylphenol, nonylphenol, several
      phthalates, and methyl phenanthrenes; Kendall correlation coefficients 0.2-0.6,
      p<0.05), indicating possible shared sources and highlighting the importance of
      considering mixtures in health studies.

PMID- 20681566
TI  - Azide-alkyne "click" conjugation of 8-aza-7-deazaadenine-DNA: synthesis, duplex
      stability, and fluorogenic dye labeling.
AB  - The internal dye labeling of DNA by the Huisgen-Meldal-Sharpless "click" reaction
      is described. Fluorogenic 9-azidomethyl anthracene 2 and 3-azido-7
      hydroxycoumarin 3 were employed in the postsynthetic functionalization of
      oligonucleotides incorporating octa-(1,7)-diynyl-8-aza-7-deaza-2'-deoxyadenosine
      1. Nucleoside 1 was prepared by Sonogashira cross coupling from the corresponding
      7-iodo compound, converted into the corresponding phosphoramidite, and
      oligonucleotides were synthesized. To evaluate the influence of ligands on the
      oligonucleotide duplex stability, benzyl azide 4 (nonpolar), and 2',3'-dideoxy
      azidothymidine 5 (AZT) (polar) were introduced along with the fluorogenic dyes 2
      and 3. DNA duplexes with octa-1,7-diynyl side chains (i.e., containing 1) are
      more stable than oligonucleotides containing 8-aza-7-deaza-2'-deoxyadenosine,
      unveiling that this side chain has steric freedom. A single conjugation by an
      anthracene residue led to a 9  degrees C T(m) increase of duplex melting.
      Contrary to 7-deazaadenine dye conjugates, the 8-aza-7-deazaadenine conjugates
      show virtually no fluorescence quenching, thereby developing almost as strong
      fluorescence as side chain click derivatives (32 and 33) in the absence of 8-aza
      7-deazaadenine moiety. Duplexes containing the 8-aza-7-deazaadenine dye conjugate
      show increased fluorescence over single-stranded DNA. Mismatches with dA, dG, and
      dC develop reduced fluorescence compared to the fully matched base pair.
      Molecular dynamics simulations revealed that the bulky dye molecules are
      accommodated well in duplex DNA.

PMID- 20681567
TI  - Effect of halide ions and carbonates on organic contaminant degradation by
      hydroxyl radical-based advanced oxidation processes in saline waters.
AB  - Advanced oxidation processes (AOPs) generating nonselective hydroxyl radicals
      (HO*) provide a broad-spectrum contaminant destruction option for the
      decontamination of waters. Halide ions are scavengers of HO* during AOP
      treatment, such that treatment of saline waters would be anticipated to be
      ineffective. However, HO* scavenging by halides converts HO* to radical reactive
      halogen species (RHS) that participate in contaminant destruction but react more
      selectively with electron-rich organic compounds. The effects of Cl-, Br-, and
      carbonates (H2CO3+HCO3-+CO3(2-)) on the UV/H2O2 treatment of model compounds in
      saline waters were evaluated. For single target organic contaminants, the impact
      of these constituents on contaminant destruction rate suppression at
      circumneutral pH followed the order Br->carbonates>Cl-. Traces of Br- in the NaCl
      stock had a greater effect than Cl- itself. Kinetic modeling of phenol
      destruction demonstrated that RHS contributed significantly to phenol
      destruction, mitigating the impact of HO* scavenging. The extent of treatment
      efficiency reduction in the presence of halides varied dramatically among
      different target organic compounds. Destruction of contaminants containing
      electron-poor reaction centers in seawater was nearly halted, while 17beta
      estradiol removal declined by only 3%. Treatment of mixtures of contaminants with
      each other and with natural organic matter (NOM) was evaluated. Although NOM
      served as an oxidant scavenger, conversion of nonselective HO* to selective
      radicals due to the presence of anions enhanced the efficiency of electron-rich
      contaminant removal in saline waters by focusing the oxidizing power of the
      system away from the NOM toward the target contaminant. Despite the importance of
      contaminant oxidation by halogen radicals, the formation of halogenated
      byproducts was minimal.

PMID- 20681568
TI  - Very black infrared detector from vertically aligned carbon nanotubes and
      electric-field poling of lithium tantalate.
AB  - Vertically aligned multiwall carbon nanotubes were grown by water-assisted
      chemical vapor deposition on a large-area lithium tantalate pyroelectric
      detector. The processing parameters are nominally identical to those by which
      others have achieved the "world's darkest substance" on a silicon substrate. The
      pyroelectric detector material, though a good candidate for such a coating,
      presents additional challenges and outcomes. After coating, a cycle of heating,
      electric field poling, and cooling was employed to restore the spontaneous
      polarization perpendicular to the detector electrodes. The detector responsivity
      is reported along with imaging as well as visible and infrared reflectance
      measurements of the detector and a silicon witness sample. We find that the
      detector responsivity is slightly compromised by the heat of processing and the
      coating properties are substrate dependent. However, it is possible to achieve
      nearly ideal values of detector reflectance uniformly less than 0.1% from 400 nm
      to 4 microm and less than 1% from 4 to 14 microm.

PMID- 20681569
TI  - Schisanartane nortriterpenoids with diverse post-modifications from Schisandra
      propinqua.
AB  - Twenty-one highly oxygenated nortriterpenoids with a schisanartane skeleton were
      isolated from the stems of Schisandra propinqua var. propinqua. These
      nortriterpenoids featured a polycyclic framework composed of 7/8/5 consecutive
      carbocycles, which were organized by similar 5/5/7/5/7/5 rings A-F and varied
      oxygen-containing rings G and H. A biosynthetic classification of these compounds
      is proposed on the basis of their diverse post-modifications.

PMID- 20681570
TI  - Apoptotic effects of polyprenylated benzoylphloroglucinol derivatives from the
      twigs of Garcinia multiflora.
AB  - With bioassay-guided fractionation, five new polyprenylated benzoylphloroglucinol
      derivatives, garcimultiflorone D (1), 18-hydroxygarcimultiflorone D (2),
      garcimultiflorone E (3), garcimultiflorone F (4), and isogarcimultiflorone F (5),
      and five known compounds, guttiferone E (6), guttiferone F (7), aristophenone A
      (8), isoxanthochymol (9), and morelloflavone (10), were isolated from the acetone
      extract of the twigs of Garcinia multiflora. The compounds were evaluated for
      their apoptotic effects against HeLa-C3 cells, which have been genetically
      engineered to produce a fluorescent biosensor capable of detecting caspase-3
      activation. Compounds 1 and 3-9 activate caspase-3 in HeLa-C3 cells within 72 h
      after treatment at a concentration of 100 microM or lower. In particular,
      compounds 6, 8, and 9 showed strong apoptosis-inducing effects at a concentration
      of 25 microM.

PMID- 20681571
TI  - Recent changes in atmospheric mercury deposition recorded in the sediments of
      remote equatorial lakes in the Rwenzori Mountains, Uganda.
AB  - We analyzed sediment cores collected from three equatorial zone lakes in the
      Rwenzori Mountains of Uganda for Hg and dated them using 210Pb. The results show
      that the lakes have been contaminated by anthropogenic Hg from atmospheric
      deposition and that the onset of Hg pollution in the region began at least by the
      late 19th century. Mercury accumulation in all sediment cores increased by about
      3-fold since the mid-19th century, a similar increase to that shown in other
      remote regions worldwide. These results from tropical high-elevation sites are
      the first for this region and contribute to our understanding of global Hg
      pollution trends. The atmospheric boundary layer is at a higher altitude in
      equatorial areas than at midlatitudes, and therefore, Hg deposition in these
      regions may not be enhanced by diurnal penetration of tropospheric air and
      associated reactive gaseous mercury as has been reported for mountain lakes at
      higher latitudes. Furthermore, the relatively low abundance of atmospheric
      oxidants may limit the amount of gaseous elemental mercury oxidized to the
      reactive gaseous form in equatorial Africa. These Rwenzori Hg records therefore
      have important implications for the understanding of Hg dynamics at high
      elevations in equatorial regions.

PMID- 20681573
TI  - Activity of physalin F in a collagen-induced arthritis model.
AB  - The effects of physalin F (1), a steroid derivative purified from Physalis
      angulata, were investigated in models of collagen-induced arthritis in DBA/1 mice
      and allergic airway inflammation in BALB/c mice. Oral treatment with 1 or
      dexamethasone caused a marked decrease in paw edema and joint inflammation when
      compared to vehicle-treated arthritic mice. In contrast, treatment with 1 had no
      effect in mice with allergic airway inflammation caused by ovalbumin
      immunization, whereas dexamethasone significantly reduced the number of
      inflammatory cells and eosinophils in the broncoalveolar lavage fluid and in lung
      sections of challenged mice. To further demonstrate that 1 acts through a
      mechanism different from that of glucocorticoids, a nuclear translocation assay
      was performed of the glucocorticoid receptor (GR) using COS-7 cells transfected
      with a plasmid encoding for a yellow fluorescent protein (YFP)-GR fusion protein.
      Untreated or treated cells with 1 had YFP staining mainly in the cytoplasm,
      whereas in dexamethasone-treated cells the YFP staining was concentrated in the
      nuclei. It is concluded that the mechanism of the immunosuppressive activity of
      physalin F is distinct from that of the glucocorticoids.

PMID- 20681574
TI  - Regulate, baby, regulate.

PMID- 20681575
TI  - Modeling Miscanthus in the soil and water assessment tool (SWAT) to simulate its
      water quality effects as a bioenergy crop.
AB  - There is increasing interest in perennial grasses as a renewable source of
      bioenergy and feedstock for second-generation cellulosic biofuels. The primary
      objective of this study is to estimate the potential effects on riverine nitrate
      load of cultivating Miscanthus x giganteus in place of conventional crops. In
      this study, the Soil and Water Assessment Tool (SWAT) is used to model miscanthus
      growth and streamwater quality in the Salt Creek watershed in Illinois. SWAT has
      a built-in crop growth component, but, as miscanthus is relatively new as a
      potentially commercial crop, data on the SWAT crop growth parameters for the crop
      are lacking. This leads to the second objective of this study, which is to
      estimate those parameters to facilitate the modeling of miscanthus in SWAT.
      Results show a decrease in nitrate load that depends on the percent land use
      change to miscanthus and the amount of nitrogen fertilizer applied to the
      miscanthus. Specifically, assuming a nitrogen fertilization rate for miscanthus
      of 90 kg-N/ha, a 10%, 25%, and 50% land use change to miscanthus will lead to
      decreases in nitrate load of about 6.4%, 16.5%, and 29.6% at the watershed
      outlet, respectively. Likewise, nitrate load may be reduced by lowering the
      fertilizer application rate, but not proportionately. When fertilization drops
      from 90 to 30 kg-N/ha the difference in nitrate load decrease is less than 1%
      when 10% of the watershed is miscanthus and less than 6% when 50% of the
      watershed is miscanthus. It is also found that the nitrate load decrease from
      converting less than half the watershed to miscanthus from corn and soybean in
      1:1 rotation surpasses that from converting the whole watershed to just soybean.

PMID- 20681576
TI  - (TD-)DFT calculation of vibrational and vibronic spectra of riboflavin in
      solution.
AB  - The photophysics and photochemistry of flavin molecules are of great interest due
      to their role for the biological function of flavoproteins. An important analysis
      tool toward the understanding of the initial photoexcitation step of flavins is
      electronic and vibrational spectroscopy, both in frequency and time domains. Here
      we present quantum chemical [(time-dependent) density functional theory ((TD
      )DFT)] calculations for vibrational spectra of riboflavin, the parent molecule of
      biological blue-light receptor chromophores, in its electronic ground (S(0)) and
      lowest singlet excited states (S(1)). Further, vibronic absorption spectra for
      the S(0) --> S(1) transition and vibronic emission spectra for the reverse
      process are calculated, both including mode mixing. Solvent effects are partially
      accounted for by using a polarizable continuum model (PCM) or a conductor-like
      screening model (COSMO). Calculated vibrational and electronic spectra are in
      good agreement with measured ones and help to assign the experimental signals
      arising from photoexcitation of flavins. In particular, upon photoexcitation a
      loss of double bond character in the polar region of the ring system is observed
      which leads to vibronic fine structure in the electronic spectra. Besides
      vibronic effects, solvent effects are important for understanding the
      photophysics of flavins in solution quantitatively.

PMID- 20681577
TI  - Organic single-crystalline p-n junction nanoribbons.
AB  - This article focuses on the growth and transport properties of organic single
      crystalline p-n junction nanoribbons. The development of organic nanoelectronics
      requires the fabrication of organic nanometer-sized p-n junctions for high
      performance devices and integrated circuits. Here we demonstrate the formation of
      single-crystalline p-n junction nanoribbons of organic semiconductors by
      selective crystallization of copper hexadecafluorophthalocyanine (F(16)CuPc, n
      type) on copper phthalocyanine (CuPc, p-type) single-crystalline nanoribbons. The
      crystallization of F(16)CuPc onto CuPc requires several parameters, including
      similar molecular structures, similar lattice constants, and pi-stacking along
      the nanoribbon axis. Ambipolar transport of the p-n junction nanoribbons was
      observed in field-effect transistors with balanced carrier mobilities of 0.05 and
      0.07 cm(2) V(-1) s(-1) for F(16)CuPc and CuPc, respectively. A basic p-n junction
      nanoribbon photovoltaic device showed current rectification under AM 1.5
      simulated light. The discrete p-n junction nanoribbons may serve as ideal systems
      for understanding basic charge-transport and photovoltaic behaviors at organic
      organic interfaces.

PMID- 20681578
TI  - Natural-abundance 43Ca solid-state NMR spectroscopy of bone.
AB  - Structural information about the coordination environment of calcium present in
      bone is highly valuable in understanding the role of calcium in bone formation,
      biomineralization, and bone diseases like osteoporosis. While a high-resolution
      structural study on bone has been considered to be extremely challenging, NMR
      studies on model compounds and bone minerals have provided valuable insight into
      the structure of bone. Particularly, the recent demonstration of (43)Ca solid
      state NMR experiments on model compounds is an important advance in this field.
      However, application of (43)Ca NMR is hampered due to the low natural-abundance
      and poor sensitivity of (43)Ca. In this study, we report the first demonstration
      of natural-abundance (43)Ca magic angle spinning (MAS) NMR experiments on bone,
      using powdered bovine cortical bone samples. (43)Ca NMR spectra of bovine
      cortical bone are analyzed by comparing to the natural-abundance (43)Ca NMR
      spectra of model compounds including hydroxyapatite and carbonated apatite. While
      (43)Ca NMR spectra of hydroxyapatite and carbonated apatite are very similar,
      they significantly differ from those of cortical bone. Raman spectroscopy shows
      that the calcium environment in bone is more similar to carbonated apatite than
      hydroxyapatite. A close analysis of (43)Ca NMR spectra reveals that the chemical
      shift frequencies of cortical bone and 10% carbonated apatite are similar but the
      quadrupole coupling constant of cortical bone is larger than that measured for
      model compounds. In addition, our results suggest that an increase in the
      carbonate concentration decreases the observed (43)Ca chemical shift frequency. A
      comparison of experimentally obtained (43)Ca MAS spectra with simulations reveal
      a 3:4 mol ratio of Ca-I/Ca-II sites in carbonated apatite and a 2.3:3 mol ratio
      for hydroxyapatite. 2D triple-quantum (43)Ca MAS experiments performed on a
      mixture of carbonated apatite and the bone protein osteocalcin reveal the
      presence of protein-bound and free calcium sites, which is in agreement with a
      model developed from X-ray crystal structure of the protein.

PMID- 20681579
TI  - Quantitative determination of multiple elements in botanicals and dietary
      supplements using ICP-MS.
AB  - A method was developed and validated for the analysis of 21 elements in various
      botanicals and dietary supplements using ICP-MS. Closed-vessel microwave
      digestion of botanicals and dietary products was assisted by various different
      procedures. The samples digested with concentrated nitric and hydrochloric acid
      (8:2) revealed the best recoveries (91-106%) using the reference certified
      materials (SRM 3280, SRM 1566b). The method was validated for linearity,
      precision, accuracy, LOD, and LOQ. The LOD was found to be in the range from
      0.005 to 1.09 ng/mL with the exception of potassium. Eleven botanicals and 21
      dietary supplements were analyzed. Among the analyzed elements, K was the most
      abundant followed by Na, Mg, Al, Ca, Mn, and Fe, whereas V, Cr, Co, Ni, Se, Cd,
      Hg, and Pb were present in low concentrations in most of the samples. The results
      showed that the ICP-MS method is a simple, fast, and reliable for the
      multielement determination in dietary supplements and botanicals.

PMID- 20681580
TI  - Moderately oxidized oils and dietary zinc and alpha-tocopheryl acetate
      supplementation: effects on the oxidative stability of rabbit plasma, liver, and
      meat.
AB  - The aim of this study was to assess the alterations in plasma, liver, and meat
      oxidative stability and alpha-tocopherol content when moderately oxidized
      sunflower oils were added to feeds and when feeds were supplemented with alpha
      tocopheryl acetate (100 mg/kg) and Zn (200 mg/kg). The effects of cooking the
      meat and its subsequent refrigeration were also studied. When the content of
      primary oxidation compounds of the oil was high, rabbit plasma, liver, and meat
      alpha-tocopherol content was reduced and meat susceptibility to oxidation
      increased. The addition of oil with a high content of secondary oxidation
      compounds (oil heated at 140  degrees C, 31 h) to feed also led to an increase in
      meat susceptibility to oxidation, although it presented an alpha-tocopherol
      content similar to that of nonheated oil. Feed supplementation with alpha
      tocopheryl acetate increased tissue alpha-tocopherol content and improved the
      oxidative stability of liver and meat. However, in the latter, it was less
      effective when oil heated at 55  degrees C was added.

PMID- 20681581
TI  - Hashing algorithms and data structures for rapid searches of fingerprint vectors.
AB  - In many large chemoinformatics database systems, molecules are represented by
      long binary fingerprint vectors whose components record the presence or absence
      of particular functional groups or combinatorial features. To speed up database
      searches, we propose to add to each fingerprint a short signature integer vector
      of length M. For a given fingerprint, the i component of the signature vector
      counts the number of 1-bits in the fingerprint that fall on components congruent
      to i modulo M. Given two signatures, we show how one can rapidly compute a bound
      on the Jaccard-Tanimoto similarity measure of the two corresponding fingerprints,
      using the intersection bound. Thus, these signatures allow one to significantly
      prune the search space by discarding molecules associated with unfavorable
      bounds. Analytical methods are developed to predict the resulting amount of
      pruning as a function of M. Data structures combining different values of M are
      also developed together with methods for predicting the optimal values of M for a
      given implementation. Simulations using a particular implementation show that the
      proposed approach leads to a 1 order of magnitude speedup over a linear search
      and a 3-fold speedup over a previous implementation. All theoretical results and
      predictions are corroborated by large-scale simulations using molecules from the
      ChemDB. Several possible algorithmic extensions are discussed.

PMID- 20681582
TI  - Simultaneous release and ADME processes of poorly water-soluble drugs:
      mathematical modeling.
AB  - The importance of studying oral drug absorption is well recognized by both
      research facilities/institutions and the pharmaceutical industry. The use of
      mathematical models can represent a very profitable and indispensable tool to
      understand oral drug absorption. Indeed, mathematical models can verify the
      correctness of the mechanisms proposed to describe drug release, absorption,
      distribution and elimination thus reducing the number of expensive and time
      consuming experiments. In this paper we develop a mathematical approach able to
      model both the polymeric particle mediated delivery and the gastrointestinal
      absorption-metabolism-excretion (ADME) of a given drug. As a model drug a poorly
      water-soluble drug (vinpocetine) in both the amorphous and nanocrystalline state
      is considered. The delivery system is obtained by drug cogrinding with a polymer
      (cross-linked polyvinilpyrrolidone). As the proposed mathematical model can
      properly fit the in vivo data on the basis of information obtained in vitro, it
      represents a powerful theoretical tool connecting in vitro and in vivo behavior.

PMID- 20681583
TI  - Novel N-methylated 8-oxoisoguanines from Pacific sponges with diverse
      neuroactivities.
AB  - Marine organisms have yielded a variety of metabolites with neuropharmacological
      applications. Here we describe the isolation and pharmacological characterization
      of four novel, neurologically active purines 1-4, isolated from Haplosclerida
      sponges collected in the Republic of Palau. The structures were determined by
      analyses of spectral and X-ray data. Compound 1 induced convulsions upon
      intracerebroventricular injection into mice, with a CD50 value of 2.4 nmol/mouse.
      Purines 2-4 were active in mouse bioassays at higher doses. The seizurogenic
      activity of 1 was correlated with inhibition of neuronal GABAergic transmission,
      with only a modest impact on excitatory signaling, in electrophysiological
      recordings from hippocampal neurons. Despite having a purine template structure,
      the inhibitory activity of 1 was not prevented by a nonselective adenosine
      receptor antagonist. Thus, 1 represents a novel substituted purine that elicits
      convulsions through its actions on inhibitory neurotransmission. These 8
      oxoisoguanine analogs comprise a new family of compounds closely related in
      structure to endogenous neurosignaling molecules and commonly used CNS
      stimulants.

PMID- 20681584
TI  - A general approach for receptor and antibody-targeted detection of native
      proteins utilizing split-luciferase reassembly.
AB  - The direct detection of native proteins in heterogeneous solutions remains a
      challenging problem. Standard methodologies rely on a separation step to
      circumvent nonspecific signal generation. We hypothesized that a simple and
      general method for the detection of native proteins in solution could be achieved
      through ternary complexation, where the conditional signal generation afforded by
      split-protein reporters could be married to the specificity afforded by either
      native receptors or specific antibodies. Toward this goal, we describe a solution
      phase split-luciferase assay for native protein detection, where we fused
      fragmented halves of firefly luciferase to separate receptor fragments or single
      chain antibodies, allowing for conditional luciferase complementation in the
      presence of several biologically significant protein targets. To demonstrate the
      utility of this strategy, we have developed and validated assay platforms for the
      vascular endothelial growth factor, the gp120 coat protein from HIV-1, and the
      human epidermal growth factor receptor 2 (HER2), a marker for breast cancer. The
      specificities of the recognition elements, CD4 and the 17b single-chain antibody,
      employed in the gp120 sensor allowed us to parse gp120s from different clades.
      Our rationally designed HER2 sensing platform was capable of discriminating
      between HER2 expression levels in several tumor cell lines. In addition,
      luminescence from reassembled luciferase was linear across a panel of cell lines
      with increasing HER2 expression. We envision that the proof of principle studies
      presented herein may allow for the potential detection of a broad range of
      biological analytes utilizing ternary split-protein systems.

PMID- 20681585
TI  - Toward a general approach for RNA-templated hierarchical assembly of split
      proteins.
AB  - The ability to conditionally turn on a signal or induce a function in the
      presence of a user-defined RNA target has potential applications in medicine and
      synthetic biology. Although sequence-specific pumilio repeat proteins can target
      a limited set of ssRNA sequences, there are no general methods for targeting
      ssRNA with designed proteins. As a first step toward RNA recognition, we utilized
      the RNA binding domain of argonaute, implicated in RNA interference, for
      specifically targeting generic 2-nucleotide, 3' overhangs of any dsRNA. We tested
      the reassembly of a split-luciferase enzyme guided by argonaute-mediated
      recognition of newly generated nucleotide overhangs when ssRNA is targeted by a
      designed complementary guide sequence. This approach was successful when
      argonaute was utilized in conjunction with a pumilio repeat and expanded the
      scope of potential ssRNA targets. However, targeting any desired ssRNA remained
      elusive as two argonaute domains provided minimal reassembled split-luciferase.
      We next designed and tested a second hierarchical assembly, wherein ssDNA guides
      are appended to DNA hairpins that serve as a scaffold for high affinity zinc
      fingers attached to split-luciferase. In the presence of a ssRNA target
      containing adjacent sequences complementary to the guides, the hairpins are
      brought into proximity, allowing for zinc finger binding and concomitant
      reassembly of the fragmented luciferase. The scope of this new approach was
      validated by specifically targeting RNA encoding VEGF, hDM2, and HER2. These
      approaches provide potentially general design paradigms for the conditional
      reassembly of fragmented proteins in the presence of any desired ssRNA target.

PMID- 20681586
TI  - Analysis of amorphous solid dispersions using 2D solid-state NMR and (1)H T(1)
      relaxation measurements.
AB  - Solid-state NMR (SSNMR) can provide detailed structural information about
      amorphous solid dispersions of pharmaceutical small molecules. In this study, the
      ability of SSNMR experiments based on dipolar correlation, spin diffusion, and
      relaxation measurements to characterize the structure of solid dispersions is
      explored. Observation of spin diffusion effects using the 2D (1)H-(13)C cross
      polarization heteronuclear correlation (CP-HETCOR) experiment is shown to be a
      useful probe of association between the amorphous drug and polymer that is
      capable of directly proving glass solution formation. Dispersions of
      acetaminophen and indomethacin in different polymers are examined using this
      approach, as well as (1)H double-quantum correlation experiments to probe
      additional structural features. (1)H-(19)F CP-HETCOR serves a similar role for
      fluorinated drug molecules such as diflunisal in dispersions, providing a rapid
      means to prove the formation of a glass solution. Phase separation is detected
      using (13)C, (19)F, and (23)Na-detected (1)H T(1) experiments in crystalline and
      amorphous solid dispersions that contain small domains. (1)H T(1) measurements of
      amorphous nanosuspensions of trehalose and dextran illustrate the ability of
      SSNMR to detect domain size effects in dispersions that are not glass solutions
      via spin diffusion effects. Two previously unreported amorphous solid dispersions
      involving up to three components and containing voriconazole and telithromycin
      are analyzed using these experiments to demonstrate the general applicability of
      the approach.

PMID- 20681588
TI  - Defining central themes in breast cancer biology by differential proteomics:
      conserved regulation of cell spreading and focal adhesion kinase.
AB  - Breast cancer is a highly heterogeneous disease, an observation that underscores
      the importance of elucidating conserved molecular characteristics, such as gene
      and protein expression, across breast cancer cell types toward providing a
      greater understanding of context-specific features central to this disease.
      Motivated by the goal of defining central biological themes across breast cancer
      cell subtypes, we conducted a global proteomic analysis of three breast cancer
      cell lines, MCF7, SK-BR-3, and MDA-MB-231, and compared these to a model of
      nontransformed mammary cells (MCF10A). Our results demonstrate modulation of
      proteins localized to the extracellular matrix, plasma membrane, and nucleus,
      along with coordinate decreases in proteins that regulate "cell spreading," a
      cellular event previously shown to be dysregulated in transformed cells. Protein
      interaction network analysis revealed the clustering of focal adhesion kinase
      (FAK), a fundamental regulator of cell spreading, with several proteins
      identified as mutually, differentially abundant across breast cancer cell lines
      that impact expression and activity of FAK, such as neprilysin and keratin 19.
      These analyses provide insights into conservation of protein expression across
      breast cancer cell subtypes, a subset of which warrants further investigation for
      their roles in the regulation of cell spreading and FAK in breast cancer.

PMID- 20681589
TI  - 129Xe NMR study of the framework flexibility of the porous hybrid MIL-53(Al).
AB  - The metal-organic framework MIL-53 exhibits a structural transition between two
      possible porous structures, so-called large-pore (lp) and narrow-pore (np) forms,
      depending on the temperature or when guest molecules are adsorbed. (129)Xe NMR
      has been used to study the lp --> np transition induced by the adsorption of
      xenon as revealed by the adsorption isotherms. The NMR spectra show that the two
      structures, characterized by two distinct lines, coexist for xenon pressures
      above 5 x 10(4) Pa at room temperature, but a complete transformation is achieved
      when the temperature is decreased. An original interpretation of the NMR results
      allowed us to quantify the rate of the structural transformation. In particular,
      at room temperature, we have shown that 28% of the channels remain open. Two
      possible interpretations of the hysteresis observed in the chemical shift
      variation versus xenon pressure are proposed.

PMID- 20681587
TI  - Effects of lead and mercury on the blood proteome of children.
AB  - Heavy metal exposure in children has been associated with a variety of
      physiological and neurological problems. The goal of this study was to utilize
      proteomics to enhance the understanding of biochemical interactions responsible
      for the health problems related to lead and mercury exposure at concentrations
      well below CDC guidelines. Blood plasma and serum samples from 34 children were
      depleted of their most abundant proteins using antibody-based affinity columns
      and analyzed using two different methods, LC-MS/MS and 2-D electrophoresis
      coupled with MALDI-TOF/MS and tandem mass spectrometry. Apolipoprotein E
      demonstrated an inverse significant association with lead concentrations (average
      being one microgram/deciliter) as deduced from LC-MS/MS and 2-D electrophoresis
      and confirmed by Western blot analysis. This coincides with prior findings that
      Apolipoprotein E genotype moderates neurobehavioral effects in individuals
      exposed to lead. Fifteen other proteins were identified by LC-MS/MS as proteins
      of interest exhibiting expressional differences in the presence of environmental
      lead and mercury.

PMID- 20681590
TI  - Polymer monoliths with exchangeable chemistries: use of gold nanoparticles as
      intermediate ligands for capillary columns with varying surface functionalities.
AB  - Newly developed porous polymer monolithic capillary columns modified with gold
      nanoparticles coated with exchangeable functionalities allow easy switching of
      separation modes by a simple ligand exchange process. These columns are prepared
      from a poly(glycidyl methacrylate-co-ethylene dimethacrylate) monolith through
      reaction of its epoxide moieties with cysteamine to afford a monolith rich in
      surface thiol groups. Gold nanoparticles prepared via in situ reduction of
      chloroauric acid within the column become attached to the surface of the pores of
      the monolith. Alternatively, a solution of colloidal gold nanoparticles can be
      pumped through the thiol modified column to achieve their attachment. While the
      first approach is faster, it affords a lower coverage of nanoparticles than the
      second method, while both methods preserve the excellent hydrodynamic properties
      that are typical of the monolithic columns. Functionalization of the surface of
      the bound gold nanoparticles is then carried out using low molecular weight thiol
      containing surface ligands. The dynamic nature of the bond between gold and these
      surface ligands enables the replacement of one surface ligand by another through
      a simple solution exchange process. This novel approach expands the application
      range of monoliths as a single column can now be used in different separations
      modes. Applications of the columns with exchangeable chemistries are demonstrated
      with the capillary electrochromatographic separation of peptides and the nano
      high-pressure liquid chromatography (HPLC) separation of proteins in both
      reversed phase and ion exchange modes.

PMID- 20681591
TI  - Enol tautomers of Watson-Crick base pair models are metastable because of nuclear
      quantum effects.
AB  - Intermolecular enol tautomers of Watson-Crick base pairs could emerge
      spontaneously via interbase double proton transfer. It has been hypothesized that
      their formation could be facilitated by thermal fluctuations and proton
      tunneling, and possibly be relevant to DNA damage. Theoretical and computational
      studies, assuming classical nuclei, have confirmed the dynamic stability of these
      rare tautomers. However, by accounting for nuclear quantum effects explicitly
      through Car-Parrinello path integral molecular dynamics calculations, we find the
      tautomeric enol form to be dynamically metastable, with lifetimes too
      insignificant to be implicated in DNA damage.

PMID- 20681592
TI  - Precisely controlled growth of heterostructured nanocrystals via a dissolution
      attachment process.
AB  - A new strategy for precisely controlling the growth of heterostructured
      nanocrystals through a dissolution-attachment process of core-shell nanocrystals
      is proposed. The secondary growth process of Cu-Au bimetallic nanocrystals (BNCs)
      comprising of a core-shell structure has been systematically investigated, which
      generates a variety of heterostructured Cu-Au-based nanocrystals. Various factors
      such as the addition of dodecanethiol and the size of the Cu-Au nanoseeds that
      contribute to the diverse growth of core-shell Cu-Au BNCs have been examined. A
      dissolution-attachment growth process is suggested on the basis of UV-vis and
      transmission electron microscopy measurements. In addition to the size, the shape
      and composition of the final nanocrystals could be controlled by this process.
      This new strategy will allow us to control the growth process of heterostructured
      nanocrystals independently from the nucleation stage, which might become much
      more complex than that of the single-component nanocrystals.

PMID- 20681593
TI  - Quantitative proteome analysis of Streptomyces coelicolor Nonsporulating liquid
      cultures demonstrates a complex differentiation process comparable to that
      occurring in sporulating solid cultures.
AB  - Streptomyces species produce many clinically important secondary metabolites and
      present a complex developmental cycle that includes programmed cell death (PCD)
      phenomena and sporulation. Industrial fermentations are usually performed in
      liquid cultures, conditions in which Streptomyces strains generally do not
      sporulate, and it was traditionally assumed that no differentiation took place.
      Recently, the existence of an early compartmentalized mycelium (MI) and a later
      multinucleated mycelium (MII) were described in solid and liquid cultures. The
      aim of this work was to compare the proteomes of the different developmental
      stages in liquid and solid S. coelicolor cultures, in order to give new insights
      in Streptomyces biology, and improve industrial fermentations. Using iTRAQ
      labeling and LC-MS/MS analysis of peptides, we demonstrate that differentiation
      in S. coelicolor liquid cultures is comparable to solid cultures. Eighty-three
      percent of all the identified proteins showed similar abundance values in MI and
      MII from liquid and solid cultures. Proteins involved in secondary metabolism
      (actinorhodin and type II polyketide biosynthesis, beta-lactamases, epimerases)
      were up-regulated in MII. Proteins involved in primary metabolism (ribosome,
      Krebs cycle, and energy production) were detected in greater abundance in MI. The
      most remarkable protein abundance differences between MII from solid and liquid
      cultures were associated with the final stages of hyphae compartmentalization and
      spore formation.

PMID- 20681594
TI  - Unique electronic structure induced high photoreactivity of sulfur-doped
      graphitic C3N4.
AB  - Electronic structure intrinsically controls the light absorbance, redox
      potential, charge-carrier mobility, and consequently, photoreactivity of
      semiconductor photocatalysts. The conventional approach of modifying the
      electronic structure of a semiconductor photocatalyst for a wider absorption
      range by anion doping operates at the cost of reduced redox potentials and/or
      charge-carrier mobility, so that its photoreactivity is usually limited and some
      important reactions may not occur at all. Here, we report sulfur-doped graphitic
      C(3)N(4) (C(3)N(4-x)S(x)) with a unique electronic structure that displays an
      increased valence bandwidth in combination with an elevated conduction band
      minimum and a slightly reduced absorbance. The C(3)N(4-x)S(x) shows a
      photoreactivity of H(2) evolution 7.2 and 8.0 times higher than C(3)N(4) under
      lambda > 300 and 420 nm, respectively. More strikingly, the complete oxidation
      process of phenol under lambda > 400 nm can occur for sulfur-doped C(3)N(4),
      which is impossible for C(3)N(4) even under lambda > 300 nm. The homogeneous
      substitution of sulfur for lattice nitrogen and a concomitant quantum confinement
      effect are identified as the cause of this unique electronic structure and,
      consequently, the excellent photoreactivity of C(3)N(4-x)S(x). The results
      acquired may shed light on general doping strategies for designing potentially
      efficient photocatalysts.

PMID- 20681595
TI  - Protein kinase-inhibitor database: structural variability of and inhibitor
      interactions with the protein kinase P-loop.
AB  - Structure-based drug design of protein-kinase inhibitors has been facilitated by
      availability of an enormous number of structures in the Protein Databank (PDB),
      systematic analyses of which can provide insight into the factors that govern
      ligand-protein kinase interactions and into the conformational variability of the
      protein kinases. In this study, a nonredundant database containing 755 unique,
      curated, and annotated PDB protein kinase-inhibitor complexes (each consisting of
      a single protein kinase chain, a ligand, and water molecules around the ligand)
      was created. With this dataset, analyses were performed of protein conformational
      variability and interactions of ligands with 11 P-loop residues. Analysis of
      ligand-protein interactions included ligand atom preference, ligand-protein
      hydrogen bonds, and the number and position of crystallographic water molecules
      around important P-loop residues. Analysis of variability in the conformation of
      the P-loop considered backbone and side-chain dihedral angles, and solvent
      accessible surface area (SASA). A distorted conformation of the P-loop was
      observed for some of the protein kinase structures. Lower SASA was observed for
      the hydrophobic residue in beta1 of several members of the AGC family of protein
      kinases. Our systematic studies were performed amino acid-by-amino acid, which is
      unusual for analyses of protein kinase-inhibitor complexes.

PMID- 20681596
TI  - Effective drug delivery, in vitro and in vivo, by carbon-based nanovectors
      noncovalently loaded with unmodified Paclitaxel.
AB  - Many new drugs have low aqueous solubility and high therapeutic efficacy.
      Paclitaxel (PTX) is a classic example of this type of compound. Here we show that
      extremely small (<40 nm) hydrophilic carbon clusters (HCCs) that are PEGylated
      (PEG-HCCs) are effective drug delivery vehicles when simply mixed with
      paclitaxel. This formulation of PTX sequestered in PEG-HCCs (PTX/PEG-HCCs) is
      stable for at least 20 weeks. The PTX/PEG-HCCs formulation was as effective as
      PTX in a clinical formulation in reducing tumor volumes in an orthotopic murine
      model of oral squamous cell carcinoma. Preliminary toxicity and biodistribution
      studies suggest that the PEG-HCCs are not acutely toxic and, like many other
      nanomaterials, are primarily accumulated in the liver and spleen. This work
      demonstrates that carbon nanomaterials are effective drug delivery vehicles in
      vivo when noncovalently loaded with an unmodified drug.

PMID- 20681597
TI  - Efficient, ordered bulk heterojunction nanocrystalline solar cells by annealing
      of ultrathin squaraine thin films.
AB  - Spin-cast 2,4-bis[4-(N,N-diisobutylamino)-2,6-dihydroxyphenyl]squaraine (SQ) thin
      films only 62 A thick are converted from amorphous to polycrystalline via
      postannealing at elevated temperatures. The surface roughness of the SQ films
      increases by a factor of 2, while selected area electron diffraction spectra
      indicate an increase in the extent of postannealed film crystallinity.
      Dichloromethane solvent annealing is also demonstrated to increase the exciton
      diffusion length of SQ by a factor of 3 over thermally annealed SQ films as a
      result of further enhancement in crystalline order. We find that the roughened
      surface features have a length scale on the order of the exciton diffusion
      length. Hence, coating the donor SQ with the acceptor, C(60), results in a nearly
      optimum controlled bulk heterojunction solar cell structure. Optimized SQ/C(60)
      photovoltaic cells have a power conversion efficiency of eta(p) = 4.6 +/- 0.1%
      (correcting for solar mismatch) at 1 sun (AM1.5G) simulated solar intensity, and
      a corresponding peak external quantum efficiency of EQE = 43 +/- 1% even for the
      very thin SQ layers employed.

PMID- 20681598
TI  - Fe(II)-catalyzed amination of aromatic C-H bonds via ring opening of 2H-azirines:
      synthesis of 2,3-disubstituted indoles.
AB  - A general method for the synthesis of 2,3-disubstituted indoles is described. The
      key feature of this method is the amination of aromatic C-H bonds via FeCl(2)
      catalyzed ring opening of 2H-azirines. The method tolerates a variety of
      functional groups such as Br, F, NO(2), OMe, CF(3), OTBS, alkenes, and OPiv. The
      method can also be extended to synthesize azaindoles.

PMID- 20681599
TI  - Synthesis and photophysical properties of expanded dehydrobenzoannulenoannulene
      trefoils.
AB  - A sequential Sonogashira cross-coupling/Pd-mediated oxidative homocoupling
      strategy affords two-dimensional dehydrobenzoannulene trefoils containing
      different sizes of the central annulenic ring system. Use of these conditions
      instead of Cu-mediated homocoupling conditions yields a structural isomer
      possessing a triphenylene ([6]annulene) core. Noticeable differences in the
      absorption and emission spectra are observed depending upon the core unit.

PMID- 20681600
TI  - Simple and efficient preparation of 2,5-disubstituted oxazoles via a metal-free
      catalyzed cascade cyclization.
AB  - A practical and simple synthesis of 2,5-disubstituted oxazoles was developed via
      an iodine-catalyzed tandem oxidative cyclization. A wide range of common
      commercial aromatic aldehydes can be used as reaction substrates, which displayed
      excellent functional group compatibility in this reaction.

PMID- 20681601
TI  - Programmable periodicity of quantum dot arrays with DNA origami nanotubes.
AB  - To fabricate quantum dot arrays with programmable periodicity, functionalized DNA
      origami nanotubes were developed. Selected DNA staple strands were biotin-labeled
      to form periodic binding sites for streptavidin-conjugated quantum dots.
      Successful formation of arrays with periods of 43 and 71 nm demonstrates precise,
      programmable, large-scale nanoparticle patterning; however, limitations in array
      periodicity were also observed. Statistical analysis of AFM images revealed
      evidence for steric hindrance or site bridging that limited the minimum array
      periodicity.

PMID- 20681604
TI  - Search for complexity generating chemical transformations by combining
      connectivity analysis and cascade transformation patterns.
AB  - Retrosynthetic analysis involved in a backward search for strategic
      disconnections is still the most powerful strategy, recently advanced by topology
      based complexity estimation, for discovering the shortest sequences of
      transformations and chemical synthesis planning. Therein, we propose an
      alternative strategy that combines backward and forward search embodied within a
      mathematical model of generating chemical transformations. The backward reasoning
      involves a new concept of the strategic bond tree for alternative multibond
      disconnections of a target molecule. In the forward direction, each combination
      of the resulted structural fragments is examined for reconstruction of the target
      structure by means of biomimetic transformation patterns that describe one-pot
      multibond forming reactions. The algorithm has been implemented into the CSB
      system, and its performance is illustrated by examples of published complex
      molecule syntheses for comparison and analysis. This paper describes the strategy
      for discovering the shortest synthetic pathways based on the multibond forming
      cascade transformations for application in synthesis design and generating
      synthetically accessible product libraries.

PMID- 20681603
TI  - Total synthesis of lehualide B by allylic alcohol-alkyne reductive cross
      coupling.
AB  - The total synthesis of anticancer marine natural product lehualide B is
      described. Overall, the synthesis proceeds in just eight steps from a simple
      gamma-pyrone, does not require the use of protecting groups, and delivers each
      nonconjugated trisubstituted alkene with high levels of stereoselection. The
      challenging C12-C16 bis-trisubstituted 1,4-diene was installed with a complex
      reductive cross-coupling reaction between a preformed Ti-alkyne complex and a
      pyrone-containing allylic alcohol.

PMID- 20681605
TI  - Design and synthesis of vanadium hydrazide gels for Kubas-type hydrogen
      adsorption: a new class of hydrogen storage materials.
AB  - In this paper we demonstrate that the Kubas interaction, a nondissociative form
      of weak hydrogen chemisorption with binding enthalpies in the ideal 20-30 kJ/mol
      range for room-temperature hydrogen storage, can be exploited in the design of a
      new class of hydrogen storage materials which avoid the shortcomings of hydrides
      and physisorpion materials. This was accomplished through the synthesis of novel
      vanadium hydrazide gels that use low-coordinate V centers as the principal Kubas
      H(2) binding sites with only a negligible contribution from physisorption.
      Materials were synthesized at vanadium-to-hydrazine ratios of 4:3, 1:1, 1:1.5,
      and 1:2 and characterized by X-ray powder diffraction, X-ray photoelectron
      spectroscopy, nitrogen adsorption, elemental analysis, infrared spectroscopy, and
      electron paramagnetic resonance spectroscopy. The material with the highest
      capacity possesses an excess reversible storage of 4.04 wt % at 77 K and 85 bar,
      corresponding to a true volumetric adsorption of 80 kg H(2)/m(3) and an excess
      volumetric adsorption of 60.01 kg/m(3). These values are in the range of the
      ultimate U.S. Department of Energy goal for volumetric density (70 kg/m(3)) as
      well as the best physisorption material studied to date (49 kg H(2)/m(3) for MOF
      177). This material also displays a surprisingly high volumetric density of 23.2
      kg H(2)/m(3) at room temperature and 85 bar--roughly 3 times higher than that of
      compressed gas and approaching the DOE 2010 goal of 28 kg H(2)/m(3). These
      materials possess linear isotherms and enthalpies that rise on coverage and have
      little or no kinetic barrier to adsorption or desorption. In a practical system
      these materials would use pressure instead of temperature as a toggle and can
      thus be used in compressed gas tanks, currently employed in many hydrogen test
      vehicles, to dramatically increase the amount of hydrogen stored and therefore
      the range of any vehicle.

PMID- 20681607
TI  - Knowledge-based scoring functions in drug design. 1. Developing a target-specific
      method for kinase-ligand interactions.
AB  - Protein kinases are attractive targets for therapeutic interventions in many
      diseases. Due to their importance in drug discovery, a kinase family-specific
      potential of mean force (PMF) scoring function, kinase-PMF, was developed to
      assess the binding of ATP-competitive kinase inhibitors. It is hypothesized that
      target-specific PMF scoring functions may achieve increased performance in
      scoring along with the growth of the PDB database. The kinase-PMF inherits the
      functions and atom types in PMF04 and uses a kinase data set of 872 complexes to
      derive the potentials. The performance of kinase-PMF was evaluated with an
      external test set containing 128 kinase crystal structures. We compared it with
      eight scoring functions commonly used in computer-aided drug design, either in
      terms of the retrieval rate of retrieving "right" conformations or a virtual
      screening study. The evaluation results clearly demonstrate that a target
      specific scoring function is a promising way to improve prediction power in
      structure-based drug design compared with other general scoring functions. To
      provide this rescoring service for researchers, a publicly accessible Web site
      was established at http://202.127.30.184:8080/scoring/index.jsp .

PMID- 20681606
TI  - In vitro selection of a DNA-templated small-molecule library reveals a class of
      macrocyclic kinase inhibitors.
AB  - DNA-templated organic synthesis enables the translation of DNA sequences into
      synthetic small-molecule libraries suitable for in vitro selection. Previously,
      we described the DNA-templated multistep synthesis of a 13,824-membered small
      molecule macrocycle library. Here, we report the discovery of small molecules
      that modulate the activity of kinase enzymes through the in vitro selection of
      this DNA-templated small-molecule macrocycle library against 36 biomedically
      relevant protein targets. DNA encoding selection survivors was amplified by PCR
      and identified by ultra-high-throughput DNA sequencing. Macrocycles corresponding
      to DNA sequences enriched upon selection against several protein kinases were
      synthesized on a multimilligram scale. In vitro assays revealed that these
      macrocycles inhibit (or activate) the kinases against which they were selected
      with IC(50) values as low as 680 nM. We characterized in depth a family of
      macrocycles enriched upon selection against Src kinase, and showed that
      inhibition was highly dependent on the identity of macrocycle building blocks as
      well as on backbone conformation. Two macrocycles in this family exhibited
      unusually strong Src inhibition selectivity even among kinases closely related to
      Src. One macrocycle was found to activate, rather than inhibit, its target
      kinase, VEGFR2. Taken together, these results establish the use of DNA-templated
      synthesis and in vitro selection to discover small molecules that modulate enzyme
      activities, and also reveal a new scaffold for selective ATP-competitive kinase
      inhibition.

PMID- 20681608
TI  - Development of a 2-aza-Cope-[3 + 2] dipolar cycloaddition strategy for the
      synthesis of quaternary proline scaffolds.
AB  - A one-pot multicomponent procedure for the synthesis of highly functionalized
      pyrrolidine rings through a domino 2-aza-Cope-[3 + 2] dipolar cycloaddition
      sequence has been demonstrated. This protocol was found to be both high-yielding
      and stereoselective for the endo cycloadduct.

PMID- 20681609
TI  - Structure-dependent all-optical switching in graphene-nanoribbon-like molecules:
      fully conjugated tri(perylene bisimides).
AB  - We present the structure-dependent nonlinear optical (NLO) properties of fully
      conjugated tri(perylene bisimides) (triPBIs) toward the understanding of the role
      of conformational flexibility and pi-electron conjugation in molecular NLO
      properties of model graphene-nanoribbon (GNR)-like molecules. In the present
      paper, we report the NLO absorption properties of the triPBIs in toluene excited
      at 532 nm with nanosecond laser pulses, where the observed transient excited
      state is determined to be a triplet and presented in the nonlinear process
      similar to the NLO properties that occur in C(60). As a result, the all-optical
      switching in both visible and near-infrared regions upon excitation at 532 nm was
      demonstrated, suggesting that the chemically synthesized model GNRs act well as
      smart all-optical switching devices without the need of external control.
      Furthermore, Raman spectral measurement was further used to characterize the
      conjugated structure properties of model compounds of functionalized graphene
      nanoribbons (F-GNRs), while the dispersion and splitting of the G-band and D-band
      in both frequency and intensity can help to distinguish the pi-conjugation and
      conformational flexibility of the two different triPBI isomers, showing the
      opportunity to tailor their optoelectronic properties by precisely controlling
      the edge orientation, edge width, and chemical termination of the edges in the
      synthesized F-GNRs.

PMID- 20681610
TI  - Resolution of 2,2-disubstituted epoxides via biocatalytic azidolysis.
AB  - A practical procedure for the enzymatic resolution of 2-alkyl-2-aryl
      disubstituted epoxides using the Codex HHDH P2E2 enzyme and sodium azide is
      reported. This method allowed the synthesis of novel regio- and enantioselective
      1-azido-2-arylpropan-2-ols in excellent yields. Furthermore, these intermediates
      were used for the preparation of enantiomerically enriched amino alcohols and
      aziridines containing a tertiary center.

PMID- 20681611
TI  - Assessing molecular transport properties of nanoporous materials by interference
      microscopy: remarkable effects of composition and microstructure on diffusion in
      the silicoaluminophosphate zeotype STA-7.
AB  - The influence of the chemical composition and of the storage and activation
      protocol on the diffusion of methanol into strongly chemically zoned crystals of
      the silicoaluminophosphate zeotype STA-7 has been investigated by interference
      microscopy. Analysis of the evolution of transient intracrystalline concentration
      profiles reveals that just-calcined SAPO STA-7 crystals with lower Si content
      (Si/(Si + P) = 0.18) exhibit higher surface permeability and bulk diffusivity
      than those with higher Si content (S/(Si + P) = 0.37). Remarkably, crystals with
      the higher Si content which were stored in the calcined form crack during
      activation along planes of weakness already present in the as-prepared crystals,
      creating fresh surfaces through regions of lower Si that are much more easily
      penetrated by the adsorbing methanol than are the original surfaces.

PMID- 20681612
TI  - Effects of mutations in Aedes aegypti sterol carrier protein-2 on the biological
      function of the protein.
AB  - Sterol carrier protein-2 (SCP-2) is a nonspecific intracellular lipid carrier
      protein. However, the molecular mechanism of ligand selectivity and the in vivo
      function of SCP-2 remain unclear. In this study, we used site-directed
      mutagenesis to investigate the ligand selectivity and in vivo function of the
      yellow fever mosquito sterol carrier protein-2 protein (AeSCP-2). Mutations to
      amino acids in AeSCP-2 known to interact with bound ligand also weakened NBD
      cholesterol binding. Substitution of amino acids in the ligand cavity changed the
      ligand specificity of mutant AeSCP-2. Overexpressing wild-type AeSCP-2 in the
      Aedes aegypti cultured Aag-2 cells resulted in an increase in the level of
      incorporation of [(3)H]cholesterol. However, overexpressing mutants that were
      deleterious to the binding of NBD-cholesterol in AeSCP-2 showed a loss of ability
      to enhance uptake of [(3)H]cholesterol in cultured cells. Interestingly, when
      [(3)H]palmitic acid was used as the substrate for incorporation in vivo, there
      was no change in the levels of incorporation with overexpression of wild-type
      protein or mutated AeSCP-2s. The in vivo data suggest that AeSCP-2 is involved in
      sterol uptake, but not fatty acid uptake. This is the first report that the
      cholesterol binding ability may directly correlate with AeSCP-2's in vivo
      function in aiding the uptake of cholesterol.

PMID- 20681613
TI  - Positional and neighboring base pair effects on the thermodynamic stability of
      RNA single mismatches.
AB  - Many naturally occurring RNA structures contain single mismatches, many of which
      occur near the ends of helices. However, previous thermodynamic studies have
      focused their efforts on thermodynamically characterizing centrally placed single
      mismatches. Additionally, algorithms currently used to predict secondary
      structure from sequence are based on two assumptions for predicting the stability
      of RNA duplexes containing this motif. It has been assumed that the thermodynamic
      contribution of small RNA motifs is independent of both its position in the
      duplex and the identity of the non-nearest neighbors. Thermodynamically
      characterizing single mismatches three nucleotides from both the 3' and 5' ends
      (i.e., off-center) of an RNA duplex and comparing these results to those of the
      same single mismatch-nearest neighbor combination centrally located have allowed
      for the investigation of these effects. The thermodynamic contributions of 13
      single mismatch-nearest neighbor combinations are reported, but only nine
      combinations are studied at all three duplex positions and are used to determine
      trends and patterns. In general, the 5'- and 3'-shifted single mismatches are
      relatively similar, on average, and more favorable in free energy than centrally
      placed single mismatches. However, close examination and comparison shows there
      are several associated idiosyncrasies with these identified general trends. These
      peculiarities may be due, in part, to the identities of the single mismatch, the
      nearest neighbors, and the non-nearest neighbors, along with the effects of the
      single mismatch position in the duplex. The prediction algorithm recently
      proposed by Davis and Znosko [Davis, A. R., and Znosko, B. M. (2008) Biochemistry
      47, 10178-10187] is used to predict the thermodynamic parameters of single
      mismatch contribution, and those values are compared to the measured values
      presented here. This comparison suggests the proposed model is a good
      approximation but could be improved by the addition of parameters that account
      for positional and/or non-nearest neighbor effects. However, more data are
      required to improve our understanding of these effects and to accurately account
      for them.

PMID- 20681614
TI  - Characterization of oligodeoxynucleotides and modifications by 193 nm
      photodissociation and electron photodetachment dissociation.
AB  - Ultraviolet photodissociation (UVPD) at 193 nm is compared to collision induced
      dissociation (CID) for sequencing and determination of modifications of
      multideprotonated 6-20-mer oligodeoxynucleotides. UVPD at 193 nm causes efficient
      charge reduction of the deprotonated oligodeoxynucleotides via electron
      detachment, in addition to extensive backbone cleavages to yield sequence ions of
      relatively low abundance, including w, x, y, z, a, a-B, b, c, and d ions.
      Although internal ions populate UVPD spectra, base loss ions from the precursor
      are absent. Subsequent CID of the charge-reduced oligodeoxynucleotides formed
      upon electron detachment, in a net process called electron photodetachment
      dissociation (EPD), results in abundant sequence ions in terms of w, z, a, a-B,
      and d products, with a marked decrease in the abundance of precursor base loss
      ions and internal fragments. Complete sequencing was possible for virtually all
      oligodeoxynucleotides studied. EPD of three modified oligodeoxynucleotides, a
      methylated oligodeoxynucleotide, a phosphorothioate-modified
      oligodeoxynucleotide, and an ethylated-oligodeoxynucleotide, resulted in specific
      and extensive backbone cleavages, specifically, w, z, a, a-B, and d products,
      which allowed the modification site(s) to be pinpointed to a more specific
      location than by conventional CID.

PMID- 20681615
TI  - Crystal structures of apo and metal-bound forms of the UreE protein from
      Helicobacter pylori: role of multiple metal binding sites.
AB  - The crystal structure of the urease maturation protein UreE from Helicobacter
      pylori has been determined in its apo form at 2.1 A resolution, bound to Cu(2+)
      at 2.7 A resolution, and bound to Ni(2+) at 3.1 A resolution. Apo UreE forms
      dimers, while the metal-bound enzymes are arranged as tetramers that consist of a
      dimer of dimers associated around the metal ion through coordination by His102
      residues from each subunit of the tetramer. Comparison of independent subunits
      from different crystal forms indicates changes in the relative arrangement of the
      N- and C-terminal domains in response to metal binding. The improved ability of
      engineered versions of UreE containing hexahistidine sequences at either the N
      terminal or C-terminal end to provide Ni(2+) for the final metal sink (urease) is
      eliminated in the H102A version. Therefore, the ability of the improved Ni(2+)
      binding versions to deliver more nickel is likely an effect of an increased local
      concentration of metal ions that can rapidly replenish transferred ions bound to
      His102.

PMID- 20681616
TI  - Coordination of Cu2+ ions to C2 symmetric pseudopeptides derived from valine.
AB  - The acid-base and coordination properties of a family of pseudopeptidic ligands
      with C(2) symmetry derived from valine (4a-e) have been studied using a variety
      of techniques as a model for metal coordination in peptides and proteins. The
      Cu(2+) cation has been selected for coordination studies, although, for
      comparison, some results for Zn(2+) are also presented. Good agreement has been
      obtained between the results obtained by potentiometric titrations, spectroscopic
      analysis, and mass spectrometry (ESI) studies. These results highlight the
      potential for the use of ESI MS for characterizing the nature of the complex
      species formed. Clearly, the Cu(2+) complexes are much more stable than the
      Zn(2+) complexes. While the role of the aliphatic spacer seems to be very minor
      in the case of the Zn(2+) complexes, revealing the ability of this cation to
      accommodate different coordination environments, this role is critical in the
      case of Cu(2+). Different complexes with 1:1 or 2:2 Cu(2+):L stoichiometries can
      be formed according to the length of the spacer and the basicity of the media.
      This is fully illustrated by the resolution of the X-ray structures of two
      different Cu(2+) complexes corresponding to the ligands containing a spacer with
      two methylene groups (ligand 4a, complex 6a [Cu(2)(H(-1)L)(2)](ClO(4))(2) with a
      2:2 stoichiometry) and a propylene spacer (4b, complex 5b [CuH(-2)L] x
      CH(3)CH(2)OH with a 1:1 stoichiometry).

PMID- 20681617
TI  - Wafer-scale high-throughput ordered growth of vertically aligned ZnO nanowire
      arrays.
AB  - This article presents an effective approach for patterned growth of vertically
      aligned ZnO nanowire (NW) arrays with high throughput and low cost at wafer scale
      without using cleanroom technology. Periodic hole patterns are generated using
      laser interference lithography on substrates coated with the photoresist SU-8.
      ZnO NWs are selectively grown through the holes via a low-temperature
      hydrothermal method without using a catalyst and with a superior control over
      orientation, location/density, and as-synthesized morphology. The development of
      textured ZnO seed layers for replacing single crystalline GaN and ZnO substrates
      extends the large-scale fabrication of vertically aligned ZnO NW arrays on
      substrates of other materials, such as polymers, Si, and glass. This combined
      approach demonstrates a novel method of manufacturing large-scale patterned one
      dimensional nanostructures on various substrates for applications in energy
      harvesting, sensing, optoelectronics, and electronic devices.

PMID- 20681618
TI  - Power of confinement: adsorbate dynamics on nanometer-scale exposed facets.
AB  - The diffusion and arrangements of CO adsorbates within nanometer-scale pores on a
      copper surface are investigated by low-temperature scanning tunneling microscopy.
      In contrast to extended terraces, confinement stabilizes dislocation lines that
      expose more than one-fourth of the adsorbate population to potentially more
      reactive adsorption configurations. Confinement allows correlation between
      adsorbate diffusivity and the number of adsorbates in the pore. A marked increase
      is found that coincides with the absence of dense films on the exposed facets. In
      combination, we find that in confinement CO molecules are much more likely to be
      at adsorption sites that allow lateral access, in contrast to the dense and
      uniform films on extended terraces.

PMID- 20681619
TI  - Noncovalent interaction of oxytetracycline with the enzyme trypsin.
AB  - Oxytetracycline (OTC) is a kind of widely used veterinary drugs. The residue of
      OTC in the environment (e.g., animal food, soils, surface, and groundwater) is
      potentially harmful. In this article, the binding mode of OTC with trypsin was
      investigated using spectroscopic and molecular docking methods. OTC can interact
      with trypsin with one binding site to form OTC-trypsin complex, resulting in
      inhibition of trypsin activity and change of the secondary structure and the
      microenvironment of the tryptophan residues of trypsin. After elimination of the
      inner filter effect, the association constant, K, was calculated to be K(290K) =
      1.36 * 10(5) L mol(-1), K(298K) = 7.30 * 10(4) L mol(-1), and K(307K) = 3.58 *
      10(4) L mol(-1) at three different temperatures. The calculated thermodynamic
      parameters (negative values of DeltaH(?) and DeltaS(?)) indicated that van der
      Waals interactions and hydrogen bonds play a major role during the interaction.
      The molecular docking study revealed that OTC bound into the S1 binding pocket,
      which illustrates that the trypsin activity was competitively inhibited by OTC,
      in accordance with the conclusion of the trypsin activity experiment. This work
      establishes a new strategy to probe the toxicity of OTC and contributes to
      clarify its molecular mechanism of toxicity in vivo. The combination of
      spectroscopic and molecular docking methods in this work can be applied to
      investigate the potential enzyme toxicity of other small organic pollutants and
      drugs.

PMID- 20681620
TI  - Base-accelerated enantioselective substitution of Morita-Baylis-Hillman
      carbonates with dialkyl phosphine oxides.
AB  - A base could accelerate the S(N)2' or S(N)2'-S(N)2' reaction of Morita-Baylis
      Hillman (MBH) carbonates with dialkyl phosphine oxides, but the judicial choice
      of an appropriate base would greatly depress this competitive S(N)2' reaction and
      allow for a highly enantioselective allylic substitution reaction with
      satisfactory yields and excellent enantioselectivities.

PMID- 20681621
TI  - One-dimensional coordination polymers from hexanuclear manganese carboxylate
      clusters featuring a {Mn(II)4Mn(III)2(mu4-O)2} core and spacer linkers.
AB  - The bridging of hexanuclear mixed-valent carboxylate coordination clusters of the
      type [Mn(6)O(2)(O(2)CR)(10)] (R = CMe(3); CHMe(2)) featuring a
      {Mn(II)(4)Mn(III)(2)(mu(4)-O)(2)} core by geometrically rigid as well as flexible
      spacer ligands such as pyrazine (pyz), nicotinamide (na), or 1,2-bis(4
      pyridyl)ethane (bpe) results exclusively in one-dimensional (1D) coordination
      polymers. The formation of {[Mn(6)O(2)(O(2)CCMe(3))(10)(Me(3)CCO(2)H)(EtOH)(na)]
      x EtOH x H(2)O}(n) (1), {[Mn(6)O(2)(O(2)CCHMe(2))(10)(pyz)(3)] x H(2)O}(n) (2),
      and {[Mn(6)O(2)(O(2)CCHMe(2))(10)(Me(2)CHCO(2)H)(EtOH)(bpe)] x Me(2)CHCO(2)H}(n)
      (3) illustrates a surprising preference of the interlinked {Mn(6)} units toward
      1D coordination chains. In the solid-state, the observed chain propagation axes
      are either colinear (1 and 3) or perpendicular (2), whereby crystal packing is
      further influenced by solvent molecules. Magnetic properties of these network
      compounds can be rationalized based on that the magnetism of discrete
      [Mn(6)O(2)(O(2)CR)(10)]-type coordination clusters with all-antiferromagnetic
      intramolecular exchange and weak antiferromagnetic intercluster coupling in 1, 2,
      and 3 follows the expected exchange coupling strength of the employed spacer
      linkers.

PMID- 20681622
TI  - The role of reversible oxidative addition in selective palladium(0)-catalyzed
      intramolecular cross-couplings of polyhalogenated substrates: synthesis of
      brominated indoles.
AB  - A Pd(0)-catalyzed C-N bond-forming reaction leading to the synthesis of
      brominated indoles is described. The use of the phosphine ligand PtBu(3) is
      necessary for reactivity. It is proposed that the bulky ligand serves to prevent
      inhibition of the catalyst by facilitating reversible oxidative addition into the
      product C-Br bond. Intramolecular coupling of a vinyl bromide in the presence of
      an aryl iodide can take place, demonstrating unprecedented levels of selectivity.

PMID- 20681623
TI  - Spectral features and stability of oligomeric pyranoanthocyanin-flavanol pigments
      isolated from red wines.
AB  - The spectral characteristics and stability of three red wine pigments (pyranoMv
      catechin, pyranoMv-epicatechin, and pyranoMv-dimer B3) toward pH variation and
      bisulfite bleaching, as well as their color stability and degradation during
      storage, have been studied. Unlike the absorbance spectra of most wine pigments,
      the intensity of which is more increased in more acidic conditions, oligomeric
      pyranoMv-flavanols have maximum absorbance at wine pH around 3.6, up to 30-50%
      higher than that in pH 1.0. This particular hyperchromic effect shown in mildly
      acidic solutions suggests the presence of intramolecular copigmentation in the
      molecule of pyranoanthocyanin-flavanols, giving rise to higher molar extinction
      coefficients around wine pH and contributing to the overall wine color. The most
      probable conformations were determined by computer-assisted model building and
      molecular mechanics. Besides exceptional stability toward pH variations,
      pyranoanthocyanin-flavanols were also shown to be entirely resistant to bleaching
      by sulfur dioxide. During a 6 month storage period, pyranoanthocyanin-flavanols
      were much more stable against degradation than the anthocyanin with the following
      order: pyranoMv-catechin > pyranoMv-dimer B3 > pyranoMv-epicatechin > carboxy
      pyranoMv ? Mv. Kinetic decomposition monitored by high-performance liquid
      chromatography-diode array detection-mass spectrometry revealed the formation of
      a new pigment (pyranone-Mv structure) and the cleavage of the interflavanic
      linkage of procyanidin dimer in the solutions containing carboxy-pyranoMv and
      pyranoMv-dimer B3, respectively. Despite some degree of decline of these
      oligomeric pyranoanthocyanins, their color intensity was surprisingly enhanced,
      and their color stability greatly improved throughout the entire storage period,
      thus contributing significantly as long-lived orange-red pigments to the
      maintenance of aged wine color.

PMID- 20681626
TI  - Cap formation engineering: from opened C60 to single-walled carbon nanotubes.
AB  - Structural control, and especially chirality control, remains a significant
      challenge in the synthesis of single-walled carbon nanotubes (SWNTs). We report
      herein a rational approach to engineering fullerene caps for growing SWNTs with
      controlled structures via chemical vapor deposition (CVD). Opening of
      fullerendione via thermal oxidation yields hemispherical caps which can initiate
      SWNT growth at their open ends. The size and structure of these caps can be
      engineered by tuning the temperature of thermal oxidation. Results show that
      pregrowth treatment of the cap is indispensable to successful growth of SWNTs.
      The temperature used for thermal oxidation strongly affects the size and
      structure of the cap and further determines the diameter distribution of the as
      grown SWNTs. Stronger oxidation treatments (450 degrees C oxidation in air)
      promote formation of thinner SWNTs, while weaker oxidation treatments (350
      degrees C oxidation in air) lead to wider SWNTs. Interestingly, SWNTs made using
      fullerene caps show steplike diameter distributions relative to SWNTs catalyzed
      by Fe nanoparticles. This cap engineering using opened C(60) provides a potential
      approach to grow SWNTs with controlled structures.

PMID- 20681627
TI  - Six-coordinate nitrosyl and nitro complexes of meso-tetratolylporphyrinatocobalt
      with trans sulfur-donor ligands.
AB  - By Fourier transform infrared and optical spectroscopy, it has been observed that
      interactions of dimethyl sulfide and tetrahydrothiophene with nitrosyl and nitro
      complexes of meso-tetra-p-tolylporphyrinatocobalt [Co(TTP)] lead to the formation
      of previously unknown six-coordinate species. Nitrosyl complexes of the general
      formula (S-donor)Co(TTP)(NO) are thermally unstable and can be seen only at low
      temperatures both in the solid state and in solution. The nitro complexes (S
      donor)Co(TTP)(NO(2)) are fairly stable at room temperature in the solid state but
      partly decompose upon dissolution. The binding constants for these complexation
      reactions were determined. In contrast to the solid-state iron nitritoporphyrin
      complexes, oxo-transfer reactions from the coordinated nitro group of
      Co(TTP)(NO(2)) to the S donors, resulting in oxidation of these sulfides and the
      formation of Co(TTP)(NO), were not observed.

PMID- 20681628
TI  - Chromium-manganese selenide carbonyl complexes: paramagnetic clusters and
      relevance to C=O activation of acetone.
AB  - The paramagnetic even-electron cluster, [Et(4)N](2)[Se(2)Cr(3)(CO)(10)], was
      found to react readily with Mn(CO)(5)Br in acetone to produce two unprecedented
      mixed chromium-manganese selenide carbonyl complexes,
      [Et(4)N][Me(2)CSe(2){Mn(CO)(4)}{Cr(CO)(5)}(2)] ([Et(4)N][1]) and
      [Et(4)N](2)[Se(2)Mn(3)(CO)(10){Cr(CO)(5)}(2)] ([Et(4)N](2)[2]). X-ray
      crystallographic analysis showed that anion 1 consisted of two Se-Cr(CO)(5)
      moieties, which were further bridged by one isopropylene group and one Mn(CO)(4)
      moiety. The dianionic cluster 2 was shown to display a Se(2)Mn(3) square
      pyramidal core with each Se atom externally coordinated by one Cr(CO)(5) group.
      The formation of complex 1, presumably via C=O activation of acetone, was further
      facilitated by acidification of the reaction of [Et(4)N](2)[Se(2)Cr(3)(CO)(10)]
      with Mn(CO)(5)Br in acetone. Complex 1 readily transformed into 2 upon treatment
      with Mn(2)(CO)(10) in a KOH/MeOH/MeCN solution. Cluster 2 was a 51-electron
      species, which readily converted to the known 49-electron cluster
      [Se(2)Mn(3)(CO)(9)](2-) upon heating and bubbling with CO. Magnetic studies of
      the even-electron cluster, [Et(4)N](2)[Se(2)Cr(3)(CO)(10)], and the odd-electron
      species, [Et(4)N](2)[2] and [PPN](2)[Se(2)Mn(3)(CO)(9)], were determined by the
      SQUID measurement to have 2, 3, and 1 unpaired electrons, respectively. In
      addition, the nature and formation of complexes 1 and 2 are discussed, and the
      magnetic properties and electrochemistry of [Se(2)Cr(3)(CO)(10)](2-), 2, and
      [Se(2)Mn(3)(CO)(9)](2-) were further studied and elucidated by molecular orbital
      calculations at the PW91 level of density functional theory.

PMID- 20681629
TI  - Identification of catalytic residues and mechanistic analysis of family GH82 iota
      carrageenases.
AB  - Marine polysaccharide degrading enzymes, and iota-carrageenases in particular,
      have received little attention in the past, although their substrate specificity
      is of interest for biotechnological applications. This is mostly a consequence of
      the lack of data about their occurrence in the marine environment. Recent
      metagenomic data mining and the genome sequencing of a marine bacterium, Zobellia
      galactanivorans, led to the identification of three new iota-carrageenase genes
      belonging to the glycoside hydrolase family GH82. The additional sequences helped
      to identify potential candidate residues as catalytic proton donor and
      nucleophile. We have identified the catalytic key residues experimentally by site
      directed mutagenesis and subsequent kinetic analysis for the iota-carrageenase
      from Alteromonas fortis CgiA1_Af. The kinetic analyses of the purified mutant
      enzymes confirm that E245 plays the role of the catalytic proton donor and D247
      the general base that activates the catalytic water molecule. The point mutations
      of three other residues, namely, Q222, H281, and Q310 in A. fortis, located in
      proximity of the active site also affect the enzyme activity. Our results
      indicate that E310 plays a role in stabilizing the substrate intermediate
      conformation, while H281 is involved in substrate binding and appears to be
      crucial for maintaining the protonation state of the catalytic proton donor E245.
      The third residue, Q222, that bridges the catalytic water molecule and a chloride
      ion, plays a crucial role in structuring the water network in the active site of
      A. fortis iota-carrageenase.

PMID- 20681630
TI  - Direct plate-reader measurement of nitric oxide released from hypoxic
      erythrocytes flowing through a microfluidic device.
AB  - The ability to perform a fluorescence-based quantitative determination of a
      biologically important analyte directly released from mammalian cells using a
      standard microtiter plate reader to measure wells integrated into a microfluidic
      device is reported. Specifically, the amount of nitric oxide (NO) released from
      flowing erythrocytes (ERYs) exposed to a hypoxic buffer is measured using a
      fluorescein-based probe. The ERYs are pumped through channels in one layer of the
      poly(dimethylsiloxane) (PDMS) device; as these cells release NO, it flows through
      a porous polycarbonate membrane to the probe. The device is then placed into a
      standard microtiter plate reader for measurement, with the entire calibration and
      analyte determination occurring simultaneously. Using this method, NO release
      from hypoxic ERYs was determined to be 6.9 +/- 1.8 microM, a significantly
      increased value in comparison to that from normoxic ERYs of 0.60 +/- 0.04 microM
      (p < 0.001, n = 4 rabbits). Furthermore, the reproducibility (reported as a %RSD)
      of measuring fluorescence standards was 3.5%. Detection limits, dynamic range,
      and optimal membrane pore diameters are also reported. This device enables the
      use of a standard high-throughput tool (the plate reader) to measure analytes in
      a microfluidic device, the ability to improve the quantitative determination of a
      relatively unstable molecule (NO), and the incorporation of a flow component and
      blood constituent into a system that can be combined with microtiter plate
      technology.

PMID- 20681631
TI  - Corrugation in exfoliated graphene: an electron microscopy and diffraction study.
AB  - Low-energy electron microscopy and microprobe diffraction are used to image and
      characterize corrugation in SiO(2)-supported and suspended exfoliated graphene at
      nanometer length scales. Diffraction line-shape analysis reveals quantitative
      differences in surface roughness on length scales below 20 nm which depend on
      film thickness and interaction with the substrate. Corrugation decreases with
      increasing film thickness, reflecting the increased stiffness of multilayer
      films. Specifically, single-layer graphene shows a markedly larger short-range
      roughness than multilayer graphene. Due to the absence of interactions with the
      substrate, suspended graphene displays a smoother morphology and texture than
      supported graphene. A specific feature of suspended single-layer films is the
      dependence of corrugation on both adsorbate load and temperature, which is
      manifested by variations in the diffraction line shape. The effects of both
      intrinsic and extrinsic corrugation factors are discussed.

PMID- 20681632
TI  - Carbon nanotube resonator in liquid.
AB  - To achieve mass measurement of biological molecules in viscous fluids using
      carbon nanotube resonators, we investigated the vibration of nanotube cantilevers
      in water using the optical detection technique. In vacuum, we often found a few
      resonance modes of nanotube vibrations. However, the nanotube lost its
      fundamental oscillation once immersed in water, suggesting a great viscous
      resistance to the nanotube vibration in water. The resonant frequency of the
      nanotube in water decreased with lowering the water temperature, corresponding to
      the natural phenomenon by which liquid viscosity tends to increase at lower
      temperatures.

PMID- 20681633
TI  - Proteome analysis of rat bone marrow mesenchymal stem cell differentiation.
AB  - Bone marrow multipotent stromal cells (or mesenchymal stem cells; MSCs) have the
      capacity for renewal and the potential to differentiate in culture into several
      cell types including osteoblasts, chondrocytes, adipocytes, cardiomyocytes, and
      neurons. This study was designed to investigate the protein expression profiles
      of rat bone marrow MSCs during differentiation into adipogenic (by dexamethasone,
      isobutylmethylxanthine, insulin, and indomethacin), cardiomyogenic (by 5
      azacytidine), chondrogenic (by ascorbic acid, insulin-transferrin-selenous acid,
      and transforming growth factor-beta1), and osteogenic (by dexamethasone, beta
      glycerophosphate, and ascorbic acid) lineages by well-known differentiation
      inducers. Proteins extracted from differentiated MSCs were separated using two
      dimensional gel electrophoresis (2-DE) and protein spots were detected using
      Sypro Ruby dye. Protein spots that were determined to be up- or down-regulated
      when the expression of corresponding spots (between weeks 1 and 2, 1 and 3, 1 and
      4) showed an increase (>=2-fold) or decrease (<=0.5-fold) were successfully
      identified by MALDI-TOF-MS. In summary, 23 new proteins were identified either up
      or down-regulated during differentiation experiments.

PMID- 20681634
TI  - Comprehensive profiling of phosphopeptides based on anion exchange followed by
      flow-through enrichment with titanium dioxide (AFET).
AB  - For large-scale analysis of phosphorylation at proteome-wide scale, a variety of
      affinity-based strategies have been developed to enrich phosphopeptide. Because
      each method differed in their specificity of isolation, the global and unbiased
      enrichment of phosphopeptides remains a major technical challenge in
      phosphoproteomics. In the present work, we demostrate that the phosphopeptide
      enrichment method based on an online continuous pH gradient in a strong anion
      exchange column (SAX method) is highly complementary to the method based on
      titanium dioxide (TiO2) affinity enrichment. Moreover, we found that the flow
      through fraction of either SAX or SCX is very phosphopeptide-rich, which
      necessitates further analysis by complementary method. Here, we developed a
      comprehensive phosphopeptides profiling strategy based on anion exchange followed
      by flow-through enrichment by TiO2 (AFET). In this strategy, SAX method was used
      as the first separation/enrichment step, which was online coupled with LC-MS/MS.
      The phosphopeptides in the SAX flow-through fraction were further enriched with
      TiO2. As a result, a more comprehensive, less biased phosphoproteome was aquired.
      Careful comparison of four different combination strategies reveal that the AFET
      method showed the advantages of more identified phosphopeptides, less mass
      spectrometry analysis time, as well as simple and automatic process step. It is
      well-suited for robust and reproducible phosphoproteomics, especially in the case
      of small amounts of sample.

PMID- 20681635
TI  - Identification of novel human adipocyte secreted proteins by using SGBS cells.
AB  - Adipose tissue is an endocrine organ secreting different types of proteins, known
      as adipokines. These adipokines play important roles in homeostasis and
      metabolism. Adipocyte differentiation leads to a change in adipokine secretion
      profile which is probably involved in disruption of homeostasis. Many adipokines
      have been identified but species differences and limitations of human adipose
      tissue material urged the need for better model systems. Here we used a human
      cell strain derived from a Simpson Golabi Behmel syndrome (SGBS) patient. SGBS
      cells have already been used in functional studies on adipocytes but not in a
      proteomic search for adipokines. In this study, 2D-MS/MS and nLC-MALDI-MS/MS were
      applied to investigate secretion profiles of SGBS adipokines. A total of 80
      secreted proteins were identified; 6 proteins are novel adipocyte secreted
      proteins, 20 proteins have not been detected before in human adipose material and
      23 additional proteins previously detected in visceral adipose tissue have been
      found here secreted by SGBS-cells of subcutaneous origin. It can be concluded
      that SGBS cells are both a valid human cell model for adipocyte secretion
      profiling and for searching for novel human (pre)adipocytes secreted proteins.

PMID- 20681636
TI  - Purification of peroxidase from Horseradish (Armoracia rusticana) roots.
AB  - Peroxidase (EC 1.11.1.7) from horseradish ( Armoracia rusticana ) roots was
      purified using a simple, rapid, three-step procedure: ultrasonication, ammonium
      sulfate salt precipitation, and hydrophobic interaction chromatography on phenyl
      Sepharose CL-4B. The preparation gave an overall yield of 71%, 291-fold
      purification, and a high specific activity of 772 U mg(-1) protein. Sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis revealed that the purified
      enzyme was homogeneous and had a molecular weight of approximately 40 kDa. The
      isolated enzyme had an isoelectric point of 8.8 and a Reinheitszahl value of 3.39
      and was stable when stored in the presence of glycerol at -20 degrees C, with
      >95% retention of original enzyme activity for at least 6 months. Maximal
      activity of purified horseradish peroxidase (HRP) was obtained under different
      optimized conditions: substrate (guaiacol and H(2)O(2)) concentrations (0.5 and
      0.3 mM, respectively), type of buffer (50 mM phosphate buffer), pH (7.0), time
      (1.0 min), and temperature of incubation (30 degrees C). In addition, the effect
      of HRP and H(2)O(2) in a neutral-buffered aqueous solution for the oxidation of
      phenol and 2-chlorophenol substrates was also studied. Different conditions
      including concentrations of phenol/2-chlorophenol, H(2)O(2), and enzyme, time,
      pH, and temperature were standardized for the maximal activity of HRP with these
      substrates; under these optimal conditions 89.6 and 91.4% oxidations of phenol
      and 2-chlorophenol were obtained, respectively. The data generated from this work
      could have direct implications in studies on the commercial production of this
      biotechnologically important enzyme and its stability in different media.

PMID- 20681637
TI  - Detection of honey adulteration by sugar syrups using one-dimensional and two
      dimensional high-resolution nuclear magnetic resonance.
AB  - The importance of honey adulteration detection has recently increased owing to
      the limited production levels in recent years and the relative high price of
      honey; therefore, this illegal practice has become more and more attractive to
      producers. Hence, the need has arisen for more effective analytical methods
      aiming at detecting honey adulteration. The present research presents an
      effective method to detect adulteration in honey falsified by intentional
      addition of different concentrations of commercial sugar syrups, using one
      dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR)
      coupled with multivariate statistical analysis. Sixty-three authentic and 63
      adulterated honey samples were analyzed. To prepare adulterated honeys, seven
      different sugar syrups normally used for nutrition of bees were used. The best
      discriminant model was obtained by 1D spectra, and leave-one-out cross-validation
      showed a predictive capacity of 95.2%. 2D NMR also furnished acceptable results
      (cross-validation correct classification 90.5%), although the (1)H NMR sequence
      is preferable because it is the simplest and fastest NMR technique.

PMID- 20681638
TI  - Hapten synthesis and polyclonal antibody-based immunoassay development for the
      analysis of forchlorfenuron in kiwifruit.
AB  - High-affinity polyclonal antibodies directed against the synthetic cytokinin
      forchlorfenuron (CPPU) were produced from three immunizing haptens with
      equivalent spacer arms located at different positions. A competitive immunoassay
      was developed with a limit of detection in buffer of 12.42 +/- 3.06 ng/L. In
      addition, the ability of the produced antibodies to recognize a set of synthetic
      CPPU analogues was studied. It was evidenced that the linker position had a
      strong impact on the specificity of the generated polyclonals, which were more
      sensitive to changes at moieties of the target analyte located furthest from the
      derivatization site of the immunogen. Finally, matrix effects of gold and green
      kiwifruit over assay parameters were evaluated. Excellent recoveries and low
      coefficients of variation were found with just a 100-fold dilution of the sample
      in buffer, hence indicating the effectiveness of the developed immunoassay as an
      analytical tool for monitoring this agrochemical in kiwifruit samples.

PMID- 20681639
TI  - Antihepatocarcinoma activity of lactic acid bacteria fermented Panax notoginseng.
AB  - Panax notoginseng was used as the medium for lactic acid bacteria fermentation to
      manufacture product with antihepatocarcinoma activity. The fermentation broth
      prepared in a 250 mL Erlenmeyer flask was found to possess antiproliferation
      activity against hepatoma Hep3B cells. At the dosage of 500 microg/mL, the
      viability of hepatoma Hep3B cells was approximately 2.2%. When the fermentation
      was scaled up to a 6.6 L fermenter, it was found that the fermentation broth
      produced at 37 degrees C for 2 days showed the highest antihepatoma activity.
      Animal study revealed that when Hep3B implanted SCID mice were treated with 1000
      mg/kg BW/day of the fermentation broth, tumor volume and tumor weight were
      reduced approximately 60% as compared to the negative control group. HPLC
      analyses showed that saponins in P. notoginseng including notoginsenoside R(1)
      and ginsenosides Rg(1), Rb(1), Rd, and Rh(4) decreased, but ginsenosides Rh(1)
      and Rg(3) increased during fermentation. LC-MS/MS revealed that the minor
      saponins ginsenoside F(1), protopanaxatriol, and notoginseng R(2) also exist in
      the fermentation product. It appears that ginsenoside Rg(3), ginsenoside Rh(1),
      and protopanaxatriol are possibly responsible for the enhanced
      antihepatocarcinoma activity of the P. notoginseng fermentation broth.

PMID- 20681641
TI  - Host-guest system of nimbin and beta-cyclodextrin or its derivatives:
      preparation, characterization, inclusion mode, and solubilization.
AB  - The inclusion complexation behavior, characterization, and binding ability of
      nimbin with beta-cyclodextrin (beta-CD) and its derivatives were investigated in
      both solution and the solid state by means of XRD, DSC, (1)H and 2D NMR, and UV
      vis spectroscopy. The results showed that the water solubility and thermal
      stability of nimbin were obviously increased in the inclusion complex with
      cyclodextrins. This satisfactory water solubility and high thermal stability of
      the nimbin/CD complexes will be potentially useful for their application as
      herbal medicines or healthcare products.

PMID- 20681640
TI  - Polysaccharides PS-G and protein LZ-8 from Reishi (Ganoderma lucidum) exhibit
      diverse functions in regulating murine macrophages and T lymphocytes.
AB  - Bioactive components in Ganoderma lucidum mainly include polysaccharides (PS-G)
      and immunomodulatory protein Ling Zhi-8 (LZ-8). These components may have diverse
      regulatory functions in the immune system. However, the PS-G preparations from
      different procedures still contained partial LZ-8 residue, indicating that the
      specific target and regulating function of PS-G and LZ-8 were not fully
      understood. In the present study, PS-G was subjected to 15% TCA for removing
      proteins and the LZ-8 detection using anti-LZ-8 monoclonal antibodies showed a
      remarkable 89.7% protein reduction of the deproteinized PS-G (dpPS-G). The
      Saccharomyces cerevisiae which expressed recombinant LZ-8 protein (rLZ-8) without
      glycosylation was generated and then compared with dpPS-G in the induction toward
      murine primary macrophage and T lymphocytic cells. The peritoneal macrophages
      from TLR4-deficient and wild type mice revealed that TLR4 was a putative receptor
      of dpPS-G, mediating the TNF-alpha, IL-1beta and IL-12p70 cytokine production and
      CD86, MHC II expression on macrophages, while rLZ-8 enhanced the production of IL
      1beta, IL-12p70, CD86, and MHC II expression by another obscure route. rLZ-8
      treated macrophages enhanced the release of IFN-gamma and IL-2 by murine CD4(+)
      and CD8(+) T cells, whereas dpPS-G treatment did not enhance the release of IFN
      gamma and IL-2. Furthermore, although the direct rLZ-8-treatment conduced
      dramatic CD154, CD44 expression on CD3(+) T cells and increased IL-2, IFN-gamma
      secretion on CD4(+) and CD8(+) T cells, the dpPS-G was incapable of priming
      CD3(+), CD4(+) or CD8(+) T cells unitarily. Taken together, these results
      demonstrated that LZ-8 could activate murine macrophages and T lymphocytes but PS
      G was merely the activator for macrophages, suggesting their diverse roles in
      activating the innate and adaptive immunity.

PMID- 20681642
TI  - Characterization of microalgal carotenoids by mass spectrometry and their
      bioavailability and antioxidant properties elucidated in rat model.
AB  - Of the total carotenoids in respective algal samples, beta-carotene in Spirulina
      platensis was 69.5%, astaxanthin and its esters in Haematococcus pluvialis was
      81.38%, and lutein in Botryococcus braunii was 74.6%. The carotenoids were
      characterized by mass spectrometry. A time-course study of carotenoids in rats
      after administration of microalgal biomass showed peak levels in plasma, liver,
      and eyes at 2, 4, and 6 h, respectively. Beta-carotene accumulation in Spirulina
      fed rats was maximum in eye tissues at 6 h. Similarly, levels of astaxanthin and
      lutein in Haematococcus- and Botryococcus-fed rats were also maximal in eye
      tissues. Astaxanthin from H. pluvialis showed better bioavailability than beta
      carotene and lutein. The antioxidant enzymes, catalase, superoxide dismutase,
      peroxidase, and TBARS were significantly high in plasma at 2 h and in liver at 4
      h, evidently offering protection from free radicals. This study implies that
      microalgae can be a good source of carotenoids of high bioavailability and
      nutraceutical value.

PMID- 20681643
TI  - Tremetone and structurally related compounds in white snakeroot ( Ageratina
      altissima ): a plant associated with trembles and milk sickness.
AB  - Ingestion of white snakeroot ( Ageratina altissima ) can cause trembles in
      livestock and milk sickness in humans. The toxicity has been associated with
      tremetol, a relatively crude, multicomponent lipophilic extract of the plant. In
      this study, 11 different compounds were isolated from white snakeroot-derived
      lipophilic extracts from 18 collections. Six of the isolated compounds have not
      been previously reported to be found in white snakeroot. High-performance liquid
      chromatography (HPLC) analysis indicated that there are three different
      chemotypes of white snakeroot from the plant samples analyzed. Elucidation of
      these chemotypes may explain the sporadic and unpredictable toxicity of white
      snakeroot to livestock and humans.

PMID- 20681644
TI  - Carotenoids modulate cytokine production in Peyer's patch cells ex vivo.
AB  - This study investigated the effects of carotenoid and capsaicin constituents of
      Capsicum on intestinal immune responses in mice. Peyer's patch (PP) cells were
      isolated from mice orally administered with capsaicin, or one of three
      carotenoids (beta-carotene, beta-cryptoxanthin, or lycopene), at 5 mg/kg/day for
      7 consecutive days. Collagenase-separated PP cells were then cultured in the
      presence or absence of concanavalin A (Con A). PP cells from mice treated with
      capsaicin, beta-carotene, or beta-cryptoxanthin all showed significantly enhanced
      interleukin (IL)-2 and interferon (IFN)-gamma production when costimulated with 5
      microg/mL Con A, with capsaicin having the greatest effect (approximately two
      times greater than in normal mice). No increase in the production of IL-2 or IL-4
      was observed when PP cells from mice were cultured without Con A. We further
      tested the combined efficacy of carotenoids and capsaicin on intestinal T-cell
      cytokine production. Oral administration of capsaicin with beta-carotene, both at
      5 mg/kg/day for 7 days, increased IFN-gamma and IL-2 production in cultured PP
      cells costimulated with Con A. In contrast, oral administration of beta
      cryptoxanthin counteracted the stimulatory effect of capsaicin treatment on T
      helper cytokine production. Flow cytometric analysis revealed that the population
      of IFN-gamma(+) and IL-4(+) cells in PPs from mice administered capsaicin and/or
      carotenoids did not change, which suggested that the effects of carotenoids and
      capsaicin on cytokine production were not due to changes in the lymphoid
      population in PPs. These results indicate that carotenoids and capsaicin, which
      are common components of foods such as Capsicum, mutually modulate T-cell immune
      responses to exogenous or endogenous inducers such as antigens in PPs, without
      changing the lymphoid population. Carotenoids modulate the potentiality of
      cytokine production in T cells or indirectly activate T cells but have no
      triggering effect such as Con A.

PMID- 20681645
TI  - Enrichment of Echinacea angustifolia with Bauer alkylamide 11 and Bauer ketone 23
      increased anti-inflammatory potential through interference with cox-2 enzyme
      activity.
AB  - Bauer alkylamide 11 and Bauer ketone 23 were previously found to be partially
      responsible for Echinacea angustifolia anti-inflammatory properties. This study
      further tested their importance using the inhibition of prostaglandin E(2)
      (PGE(2)) and nitric oxide (NO) production by RAW264.7 mouse macrophages in the
      absence and presence of lipopolysaccharide (LPS) and E. angustifolia extracts,
      phytochemical enriched fractions, or pure synthesized standards. Molecular
      targets were probed using microarray, qRT-PCR, Western blot, and enzyme assays.
      Fractions with these phytochemicals were more potent inhibitors of LPS-induced
      PGE(2) production than E. angustifolia extracts. Microarray did not detect
      changes in transcripts with phytochemical treatments; however, qRT-PCR showed a
      decrease in TNF-alpha and an increase of iNOS transcripts. LPS-induced COX-2
      protein was increased by an E. angustifolia fraction containing Bauer ketone 23
      and by pure phytochemical. COX-2 activity was decreased with all treatments. The
      phytochemical inhibition of PGE(2) production by Echinacea may be due to the
      direct targeting of COX-2 enzyme.

PMID- 20681646
TI  - Biological activity of high molecular weight phenolics from olive mill
      wastewater.
AB  - Olive oil production generates large amounts of recalcitrant compounds, the olive
      oil mill wastewater (OMWW), which represent one of the most contaminating
      effluents among those produced by the agrofood industries. Nowadays, this view
      has changed to one that recognizes the waste as a low-cost starting material rich
      in bioactive compounds, particularly biophenols, that can be extracted and
      applied as natural antioxidants for the food and pharmaceutical industries. The
      data reported in this paper indicate that the OMWW extracts, besides low
      molecular weight antioxidant phenolics such as tyrosol and hydroxytyrosol, also
      contain phenolics with a molecular weight in the range of 600-5000 Da, which
      exhibit efficient scavenging activities against hydroxyl and peroxyl radicals.
      This group of phenolics includes, besides verbascoside, isoverbascoside, and an
      oxidized form of verbascoside, a number of higher molecular weight phenolics
      arising from oxidative polymerization of hydroxytyrosol and caffeic acid.
      Overall, these higher molecular weight phenolics prove to be, in some in vitro
      tests, more efficient scavengers of hydrophilic hydroxyl radicals than
      hydroxytyrosol, which could be used for industrial applications as natural
      nontoxic antioxidants.

PMID- 20681647
TI  - Black-tea polyphenols decrease micellar solubility of cholesterol in vitro and
      intestinal absorption of cholesterol in rats.
AB  - Administration of black-tea polyphenols (BTP) simultaneously reduced lymphatic
      recovery of both (3)H-cholesterol and (14)C-trioleoylglycerol in rats that were
      cannulated in the thoracic duct. BTP decreased the in vitro micellar solubility
      of cholesterol in a dose-dependent manner. When purified theaflavins, which are
      components of BTP, were used, theaflavin-monogallates (TFMGs), theaflavin-3
      gallate (TF3G), and theaflavin-3'-gallate (TF3'G) were effective in eliminating
      cholesterol from bile salt micelles in vitro. Theaflavin (TF) and theaflavin-3,3'
      digallate (TFDG) had no effect on the micellar solubility of cholesterol. The
      concentration of bile acid in the micelles was not influenced by the addition of
      any BTPs or theaflavins. These results suggest that the reduction of micellar
      cholesterol by BTP could be important to reducing cholesterol absorption.

PMID- 20681648
TI  - Antiplatelet activity of alpha-lipoic acid.
AB  - Alpha-lipoic acid (ALA) is often used as a dietary supplement to prevent and
      treat chronic diseases associated with excessive oxidative stress. The aim of
      this study was to investigate the mechanisms of the antiplatelet activity of ALA.
      ALA significantly inhibited collagen-induced platelet aggregation, thromboxane
      B(2) (TXB(2)) formation, Ca(2+) mobilization, and protein kinase Calpha
      (PKCalpha) activation, but ALA itself increased cyclic AMP formation in rabbit
      washed platelets. However, the effects of ALA on the above platelet responses
      were markedly reversed by the addition of 2'5'-ddAdo, an adenylate cyclase
      inhibitor. Additionally, increased reactive oxygen species (ROS) formation and
      cyclooxygenase-1 activity stimulated by arachidonic acid were inhibited by ALA.
      In conclusion, we demonstrated that ALA possesses an antiplatelet activity, which
      may be associated with an elevation of cyclic AMP formation, involving subsequent
      inhibition of TXA(2), Ca(2+) mobilization, and PKCalpha-mediated pathways.
      Moreover, inhibition of ROS formation and increase of platelet membrane fluidity
      may also involve its actions.

PMID- 20681649
TI  - Investigation into the physicochemical stability and rheological properties of
      beta-carotene emulsion stabilized by soybean soluble polysaccharides and
      chitosan.
AB  - In this study, the possibility of producing stable O/W emulsions incorporating
      beta-carotene in oil droplets surrounded by multiple-layer interfacial membranes
      has been demonstrated. Emulsions were prepared using a two-stage process by
      homogenization, which relied on the adsorption of chitosan to anionic droplets
      coated with soybean soluble polysaccharides (SSPS). Results showed that the zeta
      potential, particle size, and rheological properties of emulsions were greatly
      dependent on the chitosan concentration. The electrical charge on the droplets
      increased from -34 to 58.2 mV as the chitosan concentration was increased from 0
      to 2 wt %, which indicated that chitosan adsorbed to the droplet surfaces. The
      mean particle diameter of the emulsions increased dramatically with the rise of
      chitosan concentration from 0 to 0.33 wt %, indicating the formation of large
      aggregated structures. At chitosan concentrations above 0.33 wt %, the mean
      particle diameter of emulsions decreased and reached a minimum value of 0.79 mum
      at a chitosan concentration of 0.5 wt %. Dynamic oscillatory shear tests
      indicated that the viscoelastic behavior could be enhanced by the adsorption of
      chitosan onto the SSPS-coated droplet surfaces. Chitosan concentration had a
      significant (p < 0.05) impact on the stability of beta-carotene. The least
      degradation occurred in the emulsion with chitosan concentration of 0.5%. These
      results implied that the physicochemical stability of beta-carotene emulsions has
      been improved by the adsorption of chitosan.

PMID- 20681650
TI  - Bioactive saponin from tea seed pomace with inhibitory effects against
      Rhizoctonia solani.
AB  - The present study was aimed to characterize the antifungal principles in methanol
      extract of tea ( Camellia oleifera ) seed pomace. Totally, two flavonoids,
      camelliasides A (1) and B (2), and one saponin mixture composed of
      camelliasaponin B(1) (3) were identified from the methanol extract. These
      constituents were tested for their ability to reduce the infection of cabbage
      seedlings by Rhizoctonia solani Kuhn AG-4 and to inhibit growth of the pathogen
      on potato dextrose agar plates. The saponin mixture is a potential candidate as a
      new plant-derived pesticide to control Rhizoctonia damping-off of vegetable
      seedlings.

PMID- 20681651
TI  - Glycyrrhizic acid and 18beta-glycyrrhetinic acid inhibit inflammation via
      PI3K/Akt/GSK3beta signaling and glucocorticoid receptor activation.
AB  - Many lung-related diseases, such as asthma and chronic obstructive pulmonary
      disease, are initiated by airway inflammation, and several studies indicate that
      glycyrrhizic acid (GA) alleviates inflammatory lung disease. We previously showed
      that GA and 18beta-glycyrrhetinic acid (18betaGA), found in licorice, can act as
      neuroprotective agents by promoting downstream PI3K/Akt signaling. In this study,
      we investigate the effects of GA and 18betaGA on inflammation. We show that both
      GA and 18betaGA reduce inflammatory cytokine production and its resulting anti
      inflammation. GA acts via PI3K/Akt/GSK3beta to reduce cytokine production, while
      18betaGA leads to the dissociation of a glucocorticoid receptor (GR)-HSP90
      complex to block inflammation. Our data suggest that GA and 18betaGA display anti
      inflammatory activities but inhibit inflammation via different mechanisms. We
      propose that GA and 18betaGA may be valuable biological inhibitors of lung
      inflammation. Interestingly, these data may explain why licorice is frequently
      used to treat inflammatory disease and it might be a promising nutraceutical for
      remedying inflammation.

PMID- 20681652
TI  - Microbial conversion of olive oil mill wastewaters into lipids suitable for
      biodiesel production.
AB  - Lipomyces starkey were able to survive and proliferate in the presence of olive
      oil mill wastewaters (OMW), a medium difficult to process by biological
      treatments, due to the antimicrobial activities of their phenolic components. The
      microorganisms were grown in the presence of undiluted OMW, without external
      organic supplements, producing a significant reduction of both the total organic
      carbon (TOC) and the total phenols content. The OMW treated by L. starkey showed
      a significant increase of the germination index. The preliminary dilution of OMW
      enhanced the reduction of polluting components of OMW, leading to a complete TOC
      removal, as well as to lower levels of residual phenols. The activities of
      extracellular lipases and esterases significantly increased in the course of the
      OMW fermentation. A significant increase in lipid yield was observed in L.
      starkey in the course of the OMW treatment, particularly enhanced when the
      feedstock was preliminarily diluted. The fatty acid distribution showed a
      prevalence of oleic acid, demonstrating the potential of L. starkeyi as a source
      of lipids to be used as a feedstock for the synthesis of II generation biodiesel.

PMID- 20681653
TI  - Advanced glycation end products down-regulate gap junctions in human hepatoma
      SKHep 1 cells via the activation of Src-dependent ERK1/2 and JNK/SAPK/AP1
      signaling pathways.
AB  - Hyperglycemia and advanced glycation end products (AGEs) are associated with an
      elevated risk of developing several cancers in diabetic patients. However, the
      detailed mechanisms remain to be elucidated. The mechanism of AGE-bovine serum
      albumin (BSA) on gap junction intercellular communication in human hepatoma cell
      line, SKHep 1, was investigated. Both Cx32 and Cx43 are major gap junction
      forming proteins in the liver, the loss of which has been shown to facilitate
      tumorigenesis. Although the MTT assay results showed that AGE-BSA significantly
      increased cell growth by 31%, AGE-BSA down-regulated Cx32 and Cx43 expression in
      a dose- and time-dependent manner. The present study also demonstrated that
      ERK1/2 and JNK/SAPK were significantly activated by AGE-BSA and that Src, ERK1/2,
      and JNK/SAPK inhibitors significantly reversed the reduction of Cx32 and Cx43
      proteins by AGE-BSA. Taken together, these results strongly support the
      hypothesis that Src-dependent ERK1/2 and JNK/SAPK/AP1 signaling pathways play a
      key role in AGE-BSA-mediated down-regulation of Cx32 and Cx43 protein expression
      in SKHep 1 cells.

PMID- 20681654
TI  - Apoptotic effect of quercetin on HT-29 colon cancer cells via the AMPK signaling
      pathway.
AB  - Activation of AMP-activated protein kinase (AMPK), a physiological cellular
      energy sensor, strongly suppresses cell proliferation in both nonmalignant and
      tumor cells. This study demonstrates the mechanism of quercetin-induced apoptosis
      in HT-29 colon cancer cells. Treatment of cells with quercetin significantly
      decreased cell viability in a dose-dependent manner. Notably, quercetin increased
      cell cycle arrest in the G1 phase and up-regulated apoptosis-related proteins,
      such as AMPK, p53, and p21, within 48 h. Furthermore, in vivo experiments showed
      that quercetin treatment resulted in a significant reduction in tumor volume over
      6 weeks, and apoptosis-related protein induction by quercetin was significantly
      higher in the 100 mg/kg treated group compared to the control group. All of these
      results indicate that quercetin induces apoptosis via AMPK activation and p53
      dependent apoptotic cell death in HT-29 colon cancer cells and that it may be a
      potential chemopreventive or therapeutic agent against HT-29 colon cancer.

PMID- 20681655
TI  - Genes and biochemical characterization of three novel chlorophyllase isozymes
      from Brassica oleracea.
AB  - Three full length cDNAs (BoCLH1, 1140 bp; BoCLH2, 1104 bp; BoCLH3, 884 bp)
      encoding putative chlorophyllases were cloned from the cDNA pools of broccoli
      (Brassica oleracea) florets and characterized. The amino acid sequence analysis
      indicated that these three BoCLHs contained a highly conserved lipase motif
      (GXSXG). However, only BoCLH3 lacked the His residue which is the component of
      the catalytic triad (Ser-His-Asp). N-terminal sequences of BoCLH1 and BoCLH2 were
      predicted to have typical signal sequences for the chloroplast, whereas the
      plasma membrane-targeting sequence was identified in BoCLH3. The predicted
      molecular masses of BoCLH1, 2, and 3 were 34.7, 35.3, and 23.5 kDa, respectively.
      The recombinant BoCLHs were successfully expressed in Escherichia coli for the
      biochemical characterization. The recombinant BoCLH3 showed very low
      chlorophyllase activity possibly due to its incomplete catalytic triad. BoCLH1
      and BoCLH2 showed significant differences in biochemical properties such as pH
      stability and temperature optimum. Kinetic analysis revealed that BoCLH1
      preferably hydrolyzed Mg-free chlorophyll, while BoCLH2 hydrolyzed both
      chlorophyll and Mg-free chlorophyll at a similar level. Different characteristics
      between BoCLH1 and BoCLH2 implied that they may have different physiological
      functions in broccoli. The catalytic triad of recombinant BoCLH2 was identified
      as Ser141, His247, and Asp170 by site-directed mutagenesis. It suggested that the
      three broccoli chlorophyllase isozymes were serine hydrolases.

PMID- 20681656
TI  - Effect of migrant size on diffusion in dry and hydrated polyamide 6.
AB  - Food safety authorities have already allowed the use of mathematical models to
      predict diffusion from plastic food contact materials. These models use the
      molecular weight of the migrant as a cornerstone parameter that describes the
      contribution of the migrant to the diffusion process. In this work, the
      dependence of the diffusion coefficient on the migrant size was examined through
      fluorescence recovery after photobleaching (FRAP). A model migrant series of
      fluorescent probes was used, covering a wide molecular weight range. The
      advantage and originality of the tested migrant series are associated with the
      fact that the same shape and chemical functionality are maintained regardless of
      the molecular weight of the migrants. In this way the dependence of the acquired
      data on parameters other than size is excluded. The same experiments were carried
      out in dry and hydrated polyamide 6 to evaluate the effect of polymer matrix
      mobility in the "diffusion-migrant size" relationship. The experimental data were
      compared to well-known mathematical or semiempirical approaches, verifying that
      there is a relationship between the diffusion coefficient and the size of the
      migrant. However, it is demonstrated that this relationship is also affected by
      the mobility of the polymer matrix, becoming more pronounced as the mobility of
      the matrix decreases.

PMID- 20681657
TI  - Effects of roasting on taste-active compounds of Turkish hazelnut varieties (
      Corylus avellana L.).
AB  - The effect of roasting on taste-active components of 18 native hazelnut
      varieties, grown in the Giresun province of Turkey, was assessed. Samples were
      examined for their sugars, organic acids, condensed tannins, and free phenolic
      acids. Six sugars (fructose, glucose, sucrose, myo-inositol, raffinose, and
      stachyose), seven organic acids (oxalic, maleic, citric, malic, lactic, succinic,
      and acetic), and one phenolic acid (gallic acid) were positively identified in
      natural and roasted hazelnut varieties; among these, sucrose, malic acid, and
      gallic acid predominated, respectively. Total sugars among hazelnut varieties
      ranged from 1.99 to 4.94 g/100 g, organic acids from 0.96 to 2.72 g/100 g,
      condensed tannins from 3.99 to 40.56 mg of catechin equivalents/g, and gallic
      acid from 0.159 to 0.871 mg/100 g. Differences existed in the sugar and organic
      acid contents between natural and roasted hazelnut varieties, but they did not
      follow any particular trend. Significant losses (p < 0.05) in condensed tannins (
      approximately 97.3%) and gallic acid ( approximately 66.7%) were noted when the
      hazelnuts were roasted. The present work suggests that roasting resulted in
      significant loss in condensed tannins and gallic acid due to the removal of the
      brown skin. The effect of roasting on sugars and organic acids was not
      noteworthy.

PMID- 20681658
TI  - Sugar conversion induced by the application of heat to grape must.
AB  - Two lots of the grape Trebbiano cultivar were harvested from the same vineyard 15
      days apart, and their musts were cooked in an open stainless steel pan directly
      heated by fire; the kinetics of formation or disappearance of key constituents
      was then monitored for at least 16 h. From an engineering standpoint, the vessel
      behaved like a nonisothermal batch reactor in which the volume of the grape must
      necessarily decreased while its composition changed profoundly as a result of
      chemical reactions. Brix, total titratable acids, acetic acid, malic acid, lactic
      acid (d and l), pH, water activity, 5-HMF, and phenolic and radical-scavenging
      compounds were proposed as markers of the extent of cooking for which water
      vaporization and sugar degradation were identified as the two main driving
      factors. Acid-catalyzed dehydration was hypothesized as the predominant mechanism
      for sugar degradation, assuming a direct role of water vaporization; however,
      contributions of Maillard degradation pathways and other parallel reversible
      reactions were also hypothesized. Fractional conversion of 5-HMF and radical
      scavenging compounds were proposed as quantitative markers for the extent of
      sugar degradation at, respectively, the early and advanced stages of cooking.
      Selectivity indices were also proposed as a performance criterion to design
      cooking processes in relation to sugar degradation.

PMID- 20681659
TI  - Carotenoid stability during production and storage of tomato juice made from
      tomatoes with diverse pigment profiles measured by infrared spectroscopy.
AB  - Chemical changes in carotenoids and lipids were studied during production and
      storage of canned tomato juice using ATR infrared spectroscopy and HPLC. Samples
      from 10 groups of tomatoes with different carotenoid profiles were analyzed
      fresh, after hot-break and screening, after canning, and at five different time
      points during 1 year of storage. An apparent increase of carotenoids was observed
      after hot-break due to improved extraction efficiency. This increase was
      accompanied by some degree of lipid oxidation and carotenoid isomerization.
      Canning produced the most intense changes in the lipid profile with breakdown of
      triglycerides ( approximately 1743 cm(-1)), formation of fatty acids (
      approximately 1712 cm(-1)), and degradation and isomerization of trans
      carotenoids ( approximately 960 and approximately 3006 cm(-1)). Isomerization was
      corroborated by the relative increase of HPLC areas corresponding to carotenoid
      cis isomers. Canning reduced trans-lycopene, trans-delta-carotene, trans-beta
      carotene, and trans-lutein by 30, 34, 43, and 67%, respectively. HPLC data
      indicate that canning causes a drastic reduction of tetra-cis-lycopene and
      promotes its isomerization to other geometric forms, including all-trans
      lycopene. Infrared spectra of tomato juice lipid fractions correlated well with
      the number of days in storage (SECV < 11 days, r values > 0.99), demonstrating
      continuous degradation of lipids. Results demonstrated that individual
      carotenoids and their isomeric forms behave differently during production and
      storage of canned tomato juice. Information collected by infrared spectroscopy
      complemented well that of HPLC, providing marker bands to further the
      understanding of chemical changes taking place during processing and storage of
      tomato juice.

PMID- 20681660
TI  - Chemical composition of Solanum nigrum linn extract and induction of autophagy by
      leaf water extract and its major flavonoids in AU565 breast cancer cells.
AB  - Solanum nigrum Linn (SN) belongs to the Solanaceae family, is a plant growing
      widely in south Asia, and has been used in traditional folk medicine. It is
      believed to have antipyretic, diuretic, anticancer, and hepatoprotective effects.
      During the summertime, this plant has been heavily used to supplement beverages
      to quench thirst on hot days in Taiwan and several southern Asian countries. In
      this study, the polyphenols and anthocyanidin in various parts of the SN plant
      were analyzed by HPLC. The leaves were found to be richer in polyphenols than
      stem and fruit. SN leaves contained the highest concentration of gentisic acid,
      luteolin, apigenin, kaempferol, and m-coumaric acid. However, the anthocyanidin
      existed only in the purple fruits. Additionally, the cytotoxicity of the leaf,
      stem, or fruit extract was evaluated against cancer cell lines and normal cells.
      The results showed that AU565 breast cancer cells were more sensitive to the
      extract. Furthermore, the results demonstrated a significant cytotoxic effect of
      SN leaf extract on AU565 cells that was mediated via two different mechanisms
      depending on the exposure concentrations. A low dose of SN leaf extract induced
      autophagy but not apoptosis. Higher doses (>100 microg/mL) of SN leaf extract
      could inhibit the level of p-Akt and cause cell death due to the induction of
      autophagy and apoptosis. However, these findings indicate that SN leaf extract
      induced cell death in breast cells via two distinct antineoplastic activities,
      the abilities to induce apoptosis and autophagy, therefore suggesting that it may
      provide a useful remedy to treat breast cancer.

PMID- 20681661
TI  - Gas chromatography-mass spectrometry screening for phytochemical 4
      desmethylsterols accumulated during development of Tunisian peanut kernels
      (Arachis hypogaea L.).
AB  - 4-Desmethylsterols, the main component of the phytosterol fraction, have been
      analyzed during the development of Tunisian peanut kernels ( Arachis hypogaea
      L.), Trabelsia (AraT) and Chounfakhi (AraC), which are monocultivar species, and
      Arbi (AraA), which is a wild species, by gas chromatography-mass spectrometry.
      Immature wild peanut (AraA) showed the highest contents of beta-sitosterol (554.8
      mg/100 g of oil), campesterol (228.6 mg/100 g of oil), and Delta(5)-avenasterol
      (39.0 mg/100 g of oil) followed by peanut cultivar AraC with beta-sitosterol,
      campesterol, and Delta(5)-avenasterol averages of 267.7, 92.1, and 28.6 mg/100 g
      of oil, respectively, and similarly for AraT 309.1, 108.4, and 27.4 mg/100 g of
      oil, respectively, were found. These results suggest that, in immature stages,
      phytosterol contents can be important regulator factors for the functional
      quality of peanut oil for the agro-industry chain from plant to nutraceuticals.

PMID- 20681662
TI  - Profile and characterization of the chlorogenic acids in green Robusta coffee
      beans by LC-MS(n): identification of seven new classes of compounds.
AB  - LC-MS(n) (n = 2-4) has been used to detect and characterize in green Robusta
      coffee beans 15 quantitatively minor sinapic acid and trimethoxycinnamoylquinic
      acid-containing chlorogenic acids, all reported for the first time from this
      source, with 13 of them not previously reported in nature. These comprise 3
      sinapoylquinic acid, 4-sinapoylquinic acid, and 5-sinapoylquinic acid (M(r) 398);
      3-sinapoyl-5-caffeoylquinic acid, 3-sinapoyl-4-caffeoylquinic acid, and 4
      sinapoyl-3-caffeoylquinic acid (M(r) 560); 3-(3,5-dihydroxy-4-methoxy)cinnamoyl-4
      feruloylquinic acid (M(r) 560); 3-sinapoyl-5-feruloylquinic acid, 3-feruloyl-4
      sinapoylquinic acid, and 4-sinapoyl-5-feruloylquinic acid (M(r) 574); 4
      trimethoxycinnamoyl-5-caffeoylquinic acid, 3-trimethoxycinnamoyl-5-caffeoylquinic
      acid (M(r) 574); and 5-feruloyl-3-trimethoxycinnamoylquinic acid, 3
      trimethoxycinnamoyl-4-feruloylquinic acid, and 4-trimethoxycinnamoyl-5
      feruloylquinic acid (M(r) 588). Furthermore, a series of structures including
      nine new triacyl quinic acids have been assigned on the basis of LC-MS(n)
      patterns of fragmentation, relative hydrophobicity, and analogy of fragmentation
      patterns if compared to feruloyl, caffeoyl, and dimethoxycinnamoyl quinic acids.
      Sixty-nine chlorogenic acids have now been characterized in green Robusta coffee
      beans.

PMID- 20681663
TI  - Metabolomic assessment of fermentative capability of soybean starter treated with
      high pressure.
AB  - Meju, a brick of dried fermented soybean naturally inoculated with
      microorganisms, is a starter used for producing traditional Korean fermented
      soybean products such as soybean paste (doenjang) and soy sauce (ganjang). In
      order to reduce aging time during production of soybean paste and soy sauce, high
      pressure (HP) treatment was applied to the meju starter at 500 MPa of pressure
      for 10 min at 15 degrees C. Fermentative behaviors of normal and HP-treated meju
      were assessed and compared through physicochemical and (1)H NMR-based metabolomic
      analysis. All mejues were incubated for 3 weeks at 30 degrees C. At 1 week of
      incubation, total bacterial population decreased mainly due to a reduction of
      water content by spontaneous evaporation during the incubation period. As the
      incubation time increased, glutamate, proline, betain, choline, and
      phosphocholine levels increased in both normal and HP-treated mejues, indicating
      that microorganisms in the mejues synthesize these metabolites to endure
      intracellular hyperosmotic stress induced by the reduction in water content.
      Through 3 weeks of incubation, the amino-type nitrogen contents and neutral
      protease activities in HP-treated meju were significantly higher (p < 0.05) than
      in normal meju, even though total bacterial content in HP-treated meju was 2 or 3
      times lower. Moreover, marked increases in glycerol, acetate, tyrosine, and
      choline levels were observed in HP-treated meju compared to normal meju. In
      particular, higher levels of tyrosine in HP-treated meju were consistent with the
      increased neutral protease activities compared to normal meju, indicating an
      improvement in enzyme stability with HP treatment. These findings highlight a new
      or better understanding of the influence of the HP or physical treatments on
      fermentative products in food processing, such as those associated with soybean
      paste and soy sauce, regarding metabolic behaviors in fermentative starter
      induced by HP treatment.

PMID- 20681664
TI  - Metabolism of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) in chickens.
AB  - Polybrominated diphenyl ethers (PBDEs) are an important class of persistent,
      organic pollutant that, based on previous studies in rodents, are poorly
      metabolized and bioaccumulate in lipophilic stores of the body. Because humans
      typically consume the fat and skin of chicken, a single (14)C-radiolabeled dose
      (2.7 mg/kg; 5.64 mumol/kg) of the most common PBDE in the environment, that is,
      2,2',4,4'-tetrabromodiphenyl ether (BDE-47), was administered to determine its
      metabolic disposition in male broiler chickens. Orally dosed BDE-47 was readily
      absorbed from the gut of chickens and was estimated to be 73% bioavailable.
      Cumulative tissue retention at 72 h was 60.2% of the dose. BDE-47 was deposited
      preferentially in lipophilic tissues, and the decreasing rank order of
      concentration on a wet weight basis was adipose tissue, skin, gastrointestinal
      tract, lung, carcass, muscle, liver, and kidney. When concentrations were
      adjusted for lipid content, the levels of BDE-47 in the principal edible tissues
      in chicken, that is, adipose tissue, skin, liver, and white and dark meat, were
      very similar to one another. Excretion of unbound metabolites in excreta was <1%
      of the dose, but bound radioactivity was a major component of excreta at >12% of
      the dose. Alkaline hydrolysis of bound material yielded a hydroxylated tetrabromo
      metabolite. The metabolic pathway of BDE-47 in chicken included mono-oxidation,
      mono-oxidation/debromination, and debromination. The present results suggest that
      trimming the fat and skin from chicken would substantially reduce human exposure
      to PBDEs during the consumption of chicken.

PMID- 20681665
TI  - On the losses of dissolved CO(2) during champagne serving.
AB  - Pouring champagne into a glass is far from being consequenceless with regard to
      its dissolved CO(2) concentration. Measurements of losses of dissolved CO(2)
      during champagne serving were done from a bottled Champagne wine initially
      holding 11.4 +/- 0.1 g L(-1) of dissolved CO(2). Measurements were done at three
      champagne temperatures (i.e., 4, 12, and 18 degrees C) and for two different ways
      of serving (i.e., a champagne-like and a beer-like way of serving). The beer-like
      way of serving champagne was found to impact its concentration of dissolved CO(2)
      significantly less. Moreover, the higher the champagne temperature is, the higher
      its loss of dissolved CO(2) during the pouring process, which finally constitutes
      the first analytical proof that low temperatures prolong the drink's chill and
      helps it to retain its effervescence during the pouring process. The diffusion
      coefficient of CO(2) molecules in champagne and champagne viscosity (both
      strongly temperature-dependent) are suspected to be the two main parameters
      responsible for such differences. Besides, a recently developed dynamic-tracking
      technique using IR thermography was also used in order to visualize the cloud of
      gaseous CO(2) which flows down from champagne during the pouring process, thus
      visually confirming the strong influence of champagne temperature on its loss of
      dissolved CO(2).

PMID- 20681666
TI  - New criterion for evaluation of honey: quantification of royal jelly protein
      apalbumin 1 in honey by ELISA.
AB  - The 55 kDa major protein of royal jelly, named apalbumin 1, is an authentic
      protein of honey and pollen pellet, and for its quantification an enzyme-linked
      immunosorbent assay (ELISA) was developed using specific polyclonal anti
      apalbumin 1 antibody. The limit of detection for apalbumin 1 was 2 ng mL(-1). The
      floral honeys contained apalbumin 1 as follows: acacia, 0.011%; linden, 0.010%;
      chestnut, 0.029%; rape, 0.010%; and dandelion, 0.014%. The saccharose syrup honey
      contained only 0.001% of apalbumin 1. The average amount of apalbumin 1 relating
      to the total protein content of analyzed honey samples was 23.39%, whereas in
      SCCH apalbumin 1 presented only 4.81% of total proteins of honey. Apalbumin 1 is
      thermostabile in honey at 80 degrees C incubated for 40 min. ELISA results show
      good precision in the evaluation of apalbumin 1 quantity in honey (CV ranged from
      0.69 to 4.25%).

PMID- 20681667
TI  - Sap phytochemical compositions of some bananas in Thailand.
AB  - Banana sap has some special properties relating to various phenomena such as
      browning of fruits after harvesting, permanent staining of cloth and fibers, and
      antioxidant and antibleeding properties. Analysis of banana sap using high
      performance liquid chromatography-electrospray ionization-mass spectrometry (HPLC
      ESI-MS) indicated the presence of phenolic and aromatic amino compounds of
      interest due to their special properties. With the online positive electrospray
      ionization mode (ESI), the possible structures of specific compounds were
      determined from the fragmentation patterns of each particular ion appearing in
      the mass spectra. The major compounds revealed from the sap of banana accessions,
      namely, Musa balbisiana , Musa laterita , Musa ornata , and Musa acuminata , and
      some cultivars were apigenin glycosides, myricetin glycoside, myricetin-3-O
      rutinoside, naringenin glycosides, kaempferol-3-O-rutinoside, quercetin-3-O
      rutinoside, dopamine, and N-acetylserotonin. The results indicated that there was
      a variety of phenolic and aromatic amino contents in many banana species. These
      compounds were reported to relate with biological activities. Moreover, the
      identities of these phytochemical compositions may be used as markers for banana
      diet, the assessment of physiochemical status, or the classification of banana
      clones.

PMID- 20681668
TI  - Ling-Zhi polysaccharides potentiate cytotoxic effects of anticancer drugs against
      drug-resistant urothelial carcinoma cells.
AB  - The combined effects of ling-zhi polysaccharide fraction 3 (LZP-F3) and
      anticancer drugs (cisplatin and arsenic trioxide) were examined in three human
      urothelial carcinoma (UC) cells (parental, NTUB1; cisplatin-resistant, N/P(14);
      and arsenic-resistant, N/As(0.5)). MTT assay and median-effect analysis revealed
      that LZP-F3 could profoundly reverse the chemosensitivity of N/P(14) and
      N/As(0.5) to cisplatin and arsenic, respectively, in a dose-dependent manner,
      which involved activation of p38 and down-regulation of Akt and XPA. A dose of 10
      mug/mL of LZP-F3 induced significant G1 arrest in N/P(14) and N/As(0.5) cells by
      flow cytometry, which may be mediated by the induction of p21(WAF1/CIP1). The
      combination of LZP-F3 and arsenic trioxide produced a significant synergistic
      growth inhibition of NTUB1 and N/As(0.5) cells. Similar results were also found
      in N/P(14) cells. These molecular events of combined effects involved significant
      and earlier induction of Fas, caspase 3 and 8 activation, Bax and Bad up
      regulation, Bcl-2 and Bcl-x(L) down-regulatuion, and cytochrome c release.

PMID- 20681669
TI  - Isolation and structural determination of steroidal glycosides from the bulbs of
      easter lily (Lilium longiflorum Thunb.).
AB  - The bulbs of the Easter lily ( Lilium longiflorum Thunb.) are used as a food and
      medicine in several Asian cultures, and they are cultivated as an ornamental
      plant throughout the world. A new steroidal glycoalkaloid and two new furostanol
      saponins, along with two known steroidal glycosides, were isolated from the bulbs
      of L. longiflorum. The new steroidal glycoalkaloid was identified as (22R,25R)
      spirosol-5-en-3beta-yl O-alpha-l-rhamnopyranosyl-(1-->2)-[6-O-acetyl-beta-d
      glucopyranosyl-(1-->4)]-beta-d-glucopyranoside. The new furostanol saponins were
      identified as (25R)-26-O-(beta-d-glucopyranosyl)-furost-5-en-3beta,22alpha,26
      triol 3-O-alpha-l-rhamnopyranosyl-(1-->2)-alpha-l-arabinopyranosyl-(1-->3)-beta-d
      glucopyranoside and (25R)-26-O-(beta-d-glucopyranosyl)-furost-5-en
      3beta,22alpha,26-triol 3-O-alpha-l-rhamnopyranosyl-(1-->2)-alpha-l-xylopyranosyl
      (1-->3)-beta-d-glucopyranoside. The previously known steroidal glycosides,
      (22R,25R)-spirosol-5-en-3beta-yl O-alpha-l-rhamnopyranosyl-(1-->2)-beta-d
      glucopyranosyl-(1-->4)-beta-d-glucopyranoside and (25R)-26-O-(beta-d
      glucopyranosyl)-furost-5-en-3beta,22alpha,26-triol 3-O-alpha-l-rhamnopyranosyl-(1
      ->2)-beta-d-glucopyranosyl-(1-->4)-beta-d-glucopyranoside were identified in L.
      longiflorum for the first time. These new compounds from L. longiflorum and the
      isolation methodologies employed can be used for studies on the biological role
      of steroidal glycosides in plant development and plant-pathogen interactions, as
      well as for studies in food and human health, for which little is known.

PMID- 20681670
TI  - Phenolic Antioxidants from the Leaves of Camellia pachyandra Hu.
AB  - Camellia pachyandra Hu. is a species in Camellia sect. Heterogenea (Theaceae),
      whose leaves have been used for making tea and consumed by the local people
      living in Yunnan province, China. This is the first investigation of the chemical
      constituents in the leaves of C. pachyandra, from which 22 phenolic compounds
      including nine hydrolyzable tannins (1-9), 11 flavonol glycosides (10-20), and
      two simple phenolics (21, 22) were isolated. It was noted that the leaves of the
      title plant contained no caffeine and no catechin, whereas hydrolyzable tannins
      were found to be the major constituents, of which the content of ellagitannin 5
      reached to 3.7%. All the isolates were evaluated for their antioxidant activities
      by DPPH radical scavenging and tyrosinase inhibitory assays. Though the secondary
      metabolites without caffeine and catechins are different from the commonly
      consumed tea plants, the results suggested that the leaves of C. pachyandra, rich
      in hydrolyzable tannins as potent antioxidants, could be developed as an ideal
      resource for a natural beverage without caffeine.

PMID- 20681671
TI  - Pterostilbene inhibits colorectal aberrant crypt foci (ACF) and colon
      carcinogenesis via suppression of multiple signal transduction pathways in
      azoxymethane-treated mice.
AB  - Pterostilbene (PS), a natural dimethylated analogue of resveratrol, is known to
      have diverse pharmacologic activities including anticancer, anti-inflammation,
      antioxidant, apoptosis, antiproliferation, and analgesic potential. This paper
      reports the inhibitory effect of dietary administration of pterostilbene against
      the formation of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF)
      preneoplastic lesions and adenomas in male ICR mice and delineates its possible
      molecular mechanisms. ICR mice were given two AOM injections intraperitoneal and
      continuously fed a 50 or 250 ppm pterostilbene diet for 6 or 23 weeks. It was
      found that the dietary administration of pterostilbene effectively reduced AOM
      induced formation of ACF and adenomas and inhibited the transcriptional
      activation of iNOS and COX-2 mRNA and proteins in mouse colon stimulated by AOM.
      Treatment with pterostilbene resulted in the induction of apoptosis in mouse
      colon. Moreover, administration of pterostilbene for 23 weeks significantly
      suppressed AOM-induced GSK3beta phosphorylation and Wnt/beta-catenin signaling.
      It was also found that pterostilbene significantly inhibited AOM-induced
      expression of VEGF, cyclin D1, and MMPs in mouse colon. Furthermore,
      pterostilbene markedly inhibited AOM-induced activation of Ras,
      phosphatidylinositol 3 kinase/Akt, and EGFR signaling pathways. All of these
      results revealed that pterostilbene is an effective antitumor agent as well as
      its inhibitory effect through the down-regulation of inflammatory iNOS and COX-2
      gene expression and up-regulation of apoptosis in mouse colon, suggesting that
      pterostilbene is a novel functional agent capable of preventing inflammation
      associated colon tumorigenesis.

PMID- 20681672
TI  - Effect of chemical randomization on positional distribution and stability of
      omega-3 oil triacylglycerols.
AB  - Randomization has been commonly used to modify the chemical and physical
      properties of natural fats and oils. In this study, seal blubber oil (SBO) and
      menhaden oil (MHO) were modified through chemical randomization using sodium
      methoxide, and the effect on positional distribution of fatty acids was
      investigated using gas chromatography (GC) and (13)C nuclear magnetic resonance
      (NMR) spectroscopy. The effect of randomization on the stability of the original
      oils and their randomized counterparts was analyzed by comparing conjugated
      dienes and thiobarbituric acid reactive substances (TBARS) values after
      accelerated oxidation at 60 degrees C for 4 days. The omega-3 polyunsaturated
      fatty acids (PUFA) were distributed more evenly among the terminal sn-1,3
      positions and the middle sn-2 position in chemically randomized oils when
      compared to the starting oils. The effect was more pronounced for SBO with omega
      3 PUFA attached preferentially to sn-1,3 positions of triacylglycerols before
      randomization, and it was less pronounced for MHO, which contained omega-3 PUFA
      more evenly distributed before randomization. However, different levels of
      commonly known omega-3 fatty acids, namely, docosahexaenoic acid (DHA),
      docosapentaenoic acid (DPA), eicosapentaenoic acid (EPA), and stearidonic acid
      (STA), were obtained in both original and randomized oils from GC and (13)C NMR
      spectroscopy. The stability of the randomized oils was also affected to different
      degrees, depending on the storage time.

PMID- 20681673
TI  - Characterization of selected wild Mediterranean fruits and comparative efficacy
      as inhibitors of oxidative reactions in emulsified raw pork burger patties.
AB  - In the present study, water, ethanolic, and methanolic extracts from seven
      selected wild fruits originally from the Mediterranean area, namely, strawberry
      tree ( Arbutus unedo L., AU), azarole ( Crataegus azarolus L., CA), common
      hawthorn ( Crataegus monogyna L., CM), blackthorn ( Prunus spinosa L., PS), dog
      rose ( Rosa canina L., RC), elm-leaf blackberry ( Rubus ulmifolius Schott, RU),
      and rowan ( Sorbus aucuparia L., SA), were analyzed for the total amount and
      profile of phenolic compounds and for the in vitro antioxidant activity against
      the DPPH and ABTS radicals (study 1). The seven fruits showed different chemical
      compositions, which consequently led to different antioxidant potentials. Among
      the seven fruits initially analyzed, AU, CM, RC, and RU had the highest amount of
      phenolic compounds and displayed the greatest antioxidant activity in vitro.
      Extracts from these four fruits were tested as inhibitors of lipid oxidation in
      raw pork burger patties subjected to refrigerated storage at 2 degrees C for 12
      days (study 2). The quantitative measurements of thiobarbituric acid reactive
      substances (TBA-RS), hexanal content, and color stability were used as indicators
      of oxidative reactions. The four selected fruits displayed intense antioxidant
      activity against lipid oxidation, which highlights the potential usage of these
      fruits as ingredients for the manufacture of healthy meat products. Among them,
      RC and AU were particularly efficient as their protective effect against lipid
      oxidation was more intense than that displayed by quercetin (230 mg/kg of burger
      patty).

PMID- 20681674
TI  - Pyranoanthocyanins: a theoretical investigation on their antioxidant activity.
AB  - The antioxidant radical scavenging capacity of pyranoanthocyanins present in aged
      wine and coming from the chemical transformation undergone by anthocyanins was
      theoretically explored by DFT/B3LYP methods. The two main working mechanisms (H
      atom donation and single-electron transfer) were investigated, and the O-H bond
      dissociation energy (BDE) and ionization potential (IP) parameters were computed
      in the gas phase and in water and benzene solutions. Results indicated that
      systems possessing the catechol functionality as well as the o-dimethoxy motif
      are good candidates to donate a H atom to the free radicals, inactivating them.
      Compounds with a higher degree of electron delocalization may work within the
      single-electron transfer mechanism. Results provided molecular insight into
      factors that influence the radical scavenging potential of anthocyanins and then
      the beneficial health effects of these wine pigments.

PMID- 20681675
TI  - Beta-glucosidase isolated from soybean okara shows specificity toward glucosyl
      isoflavones.
AB  - A novel beta-glucosidase was isolated from soybean okara in this study. Along
      with the beta-glucosidase, a considerable basic 7S globulin of soybean was
      obtained in the initial extraction products. The protein samples pretreated with
      130 mM dithiothreitol before the step of CM-Sepharose chromatography could
      greatly enhance the separation of the targeted beta-glucosidase from the
      impurities. The purified beta-glucosidase was found to be a monomer estimated to
      be 75 kDa by SDS-PAGE. The optimal temperature and pH for this beta-glucosidase
      were 45 degrees C and 4.5, respectively. The activity of this purified beta
      glucosidase was completely inhibited by 1 mM Hg(2+) or 10 mM Al(3+) ion, and
      glucose and mannose also affected the activity. This beta-glucosidase possessed
      strict specificity toward glucosyl isoflavones but not malonylglucosidic
      conjugates of isoflavones of soybean. The N-terminal amino acid sequence of the
      beta-glucosidase was EYLKYKDPKA-, which highly matched that of glycosidases in
      maize (Zea mays) and wheat (Triticum asetivum).

PMID- 20681676
TI  - Potentially deadly carcinogenic chromium redox cycle involving peroxochromium(IV)
      and glutathione.
AB  - Peroxochromium(IV) complexes are putative DNA-damaging and mutagenic agents in
      chromium(VI)-mediated carcinogenesis. The reaction between
      aquaethylenediaminebis(peroxo)chromium(IV) and glutathione at neutral pH exhibits
      a cyclic redox process displaying a persistent recycling of Cr(IV) and Cr(VI)
      with the intervention of chromium(V) intermediates. The coordination by a
      glutathione molecule triggers an autooxidation of the Cr(IV)-peroxo complex to
      Cr(VI) via an internal electron-transfer process followed by reduction to Cr(IV)
      via metastable chromium(V) intermediates. The cycle is repeated by the second
      peroxo species. The Cr(V) and -(IV) intermediates have been characterized as mono
      and bisglutathionato complexes with or without a coordinated peroxo moiety.
      These intermediates are capable of damaging DNA, as evidenced by single strand
      breaks and DNA oxidation. The implication here is that the potential for a
      persistent, if not perpetual, deadly chromium carcinogenic cycle exists in the
      cellular milieu through the assistance of molecular oxygen and glutathione.

PMID- 20681677
TI  - Detection of the photosystem I:ferredoxin complex by backscattering
      interferometry.
AB  - The dissociation constant K(d) of the photosystem I (PSI):ferredoxin complex has
      been measured by backscattering interferometry (BSI) with cyanobacterial PSI (350
      kDa) and ferredoxin (10.5 kDa). The BSI signal, consisting of shifts for
      interference fringes resulting from a change in refractive index due to complex
      formation, was monitored as ferredoxin concentration was titrated. K(d) values of
      0.14-0.38 microM were obtained with wild-type PSI whereas no complex was
      detectable with a PSI mutant containing a single mutation (R39Q) in the PsaE
      extrinsic subunit. These results are in quantitative agreement with previous
      functional determinations consisting in the detection of fast electron transfer
      within the complex. They provide evidence that the main contribution for the high
      affinity binding of ferredoxin to PSI is due to a single region of PsaE
      comprising arginine 39. They do not support the existence of a secondary binding
      site that could have escaped functional detection.

PMID- 20681678
TI  - Noninvasive remote-controlled release of drug molecules in vitro using magnetic
      actuation of mechanized nanoparticles.
AB  - Mesoporous silica nanoparticles are useful nanomaterials that have demonstrated
      the ability to contain and release cargos with mediation by gatekeepers. Magnetic
      nanocrystals have the ability to exhibit hyperthermic effects when placed in an
      oscillating magnetic field. In a system combining these two materials and a
      thermally sensitive gatekeeper, a unique drug delivery system can be produced. A
      novel material that incorporates zinc-doped iron oxide nanocrystals within a
      mesoporous silica framework that has been surface-modified with pseudorotaxanes
      is described. Upon application of an AC magnetic field, the nanocrystals generate
      local internal heating, causing the molecular machines to disassemble and
      allowing the cargos (drugs) to be released. When breast cancer cells (MDA-MB-231)
      were treated with doxorubicin-loaded particles and exposed to an AC field, cell
      death occurred. This material promises to be a noninvasive, externally controlled
      drug delivery system with cancer-killing properties.

PMID- 20681679
TI  - Reagent-dependent formation of C-C and C-F bonds in Pt complexes: an unexpected
      twist in the electrophilic fluorination chemistry.
AB  - Cyclometalated platinum(II) complexes (C-P)Pt(Aryl)py undergo oxidative addition
      reaction upon treatment with electrophilic fluorination reagents, XeF(2) or N
      fluoro-2,4,6-trimethylpyridinium tetrafluoroborate, giving eventually products of
      C-C coupling. However, when aryl = mesityl, the two reagents give completely
      different products: the N-F salt still favors the C-C coupling reaction while
      XeF(2) gives the unprecedented benzylic fluorination of one of the ortho-methyl
      groups of the mesityl ligand.

PMID- 20681680
TI  - Enantioselective synthesis of boron-substituted quaternary carbons by NHC-Cu
      catalyzed boronate conjugate additions to unsaturated carboxylic esters, ketones,
      or thioesters.
AB  - A Cu-catalyzed method for enantioselective boronate conjugate additions to
      trisubstituted alkenes of acyclic alpha,beta-unsaturated carboxylic esters,
      ketones, and thioesters is disclosed. All transformations are promoted by 5 mol %
      of a chiral monodentate NHC-Cu complex, derived from a readily available C(1)
      symmetric imidazolinium salt, and in the presence of commercially available
      bis(pinacolato)diboron. Reactions are efficient (typically, 60% to >98% yield
      after purification) and deliver the desired beta-boryl carbonyls in up to >98:2
      enantiomer ratio (er). Processes involving unsaturated thioesters proceed with
      higher enantioselectivity (vs carboxylic esters or ketones), and the resulting
      products can be functionalized by Ag-mediated or Pd-catalyzed reactions that
      furnish the derived carboxylic ester or various ketones. Routine oxidation
      affords beta-hydroxy ketones or carboxylic esters, ketone aldol products that
      cannot be otherwise prepared efficiently by an alternative catalytic
      enantioselective protocol.

PMID- 20681681
TI  - Enantioselective synthesis of allylboronates bearing a tertiary or quaternary B
      substituted stereogenic carbon by NHC-Cu-catalyzed substitution reactions.
AB  - Allylic substitutions that afford alpha-substituted allylboronates bearing B
      substituted tertiary or quaternary carbon stereogenic centers are presented. C-B
      bond-forming reactions, catalyzed by chiral bidentate Cu-NHC complexes, are
      performed in the presence of commercially available bis(pinacolato)diboron.
      Transformations proceed in high yield (up to >98%) and site selectivity (>98%
      S(N)2'), and in up to >99:1 enantiomer ratio. Trans- or cis-disubstituted alkenes
      can be used; alkyl- (linear as well as branched) and aryl-trisubstituted allylic
      carbonates serve as effective substrates. Allylboronates that bear a quaternary
      carbon center are air-stable and can be easily purified by silica gel
      chromatography; in contrast, secondary allylboronates cannot be purified in the
      same manner and are significantly less stable. Oxidation of the enantiomerically
      enriched products furnishes secondary or tertiary allylic alcohols, valuable
      small molecules that cannot be easily obtained in high enantiomeric purity by
      alternative synthesis or kinetic resolution approaches.

PMID- 20681682
TI  - Tailoring DNA structure to increase target hybridization kinetics on surfaces.
AB  - We report a method for increasing the rate of target hybridization on DNA
      functionalized surfaces using a short internal complement DNA (sicDNA) strand.
      The sicDNA causes up to a 5-fold increase in association rate by inducing a
      conformational change that extends the DNA away from the surface, making it more
      available to bind target nucleic acids. The sicDNA-induced kinetic enhancement is
      a general phenomenon that occurred with all sequences and surfaces investigated.
      Additionally, the process is selective and can be used in multicomponent systems
      to controllably and orthogonally "turn on" specific sequences by the addition of
      the appropriate sicDNA. Finally, we show that sicDNA is compatible with systems
      used in gene regulation, intracellular detection, and microarrays, suggesting
      several potential therapeutic, diagnostic, and bioinformatic applications.

PMID- 20681683
TI  - Rapid release of entrapped contents from multi-functionalizable, surface cross
      linked micelles upon different stimulation.
AB  - Hydrophobic guests such as pyrene could be readily trapped inside the micelles of
      an alkynylated surfactant in the presence of an azide-functionalized cross-linker
      using the click reaction. The cross-linker was designed to contain cleavable
      bonds such as geminal diol, disulfide, and acetal. The resulting pyrene
      containing water-soluble nanoparticle was under electrostatic stress when diluted
      below the CMC of the surfactant. Extremely rapid (<1 min) release of the
      hydrophobic content was observed when the cross-linker was cleaved. This method
      combines the ease of physical entrapment and the precision of chemical ligation,
      and potentially is highly useful in the delivery and controlled release of
      pharmaceutical agents.

PMID- 20681684
TI  - Anticancer drug release from a mesoporous silica based nanophotocage regulated by
      either a one- or two-photon process.
AB  - An excellent mesoporous silica nanoparticle (MSN) based drug deliver system (DDS)
      was reported for regulated anticancer drug release upon the irradiation of either
      one- or two-photon excitation. In this system, the coumarin grafted on MSN acted
      as both the "phototrigger" for the drug release and fluorescence group for cell
      luminescence imaging. External light manipulations such as changing irradiation
      wavelength, intensity, and time can regulate the release of the anticancer drug
      precisely. Biological studies in vitro suggest that the drug carrier can
      effectively deliver the anticancer drug into intracellular environs and, hence,
      promote the drug action to kill the cancer cells upon irradiation. We envision
      that the good biocompatibility, cellular uptake property, and efficient
      photoregulated drug release will be of great benefit to future controlled release
      in vivo biomedical applications.

PMID- 20681685
TI  - Is there a lower limit to the CC bonding distances in neutral radical pi-dimers?
      The case of phenalenyl derivatives.
AB  - Two-electron multicenter (2e/mc) bonding of phenalenyl (PHYL) pi-dimers was found
      to be significantly affected by the electron density on the bonding active sites.
      The computational analysis shows that, upon appropriate beta-substitutions, the
      newly introduced dimers have the shortest and strongest covalent bonding
      interactions seen in any neutral pi-dimer. The unusual strengthening of the
      bonding was attributed to the reduced lone pair bond weakening effect, LPBWE,
      upon substitutions with electron-withdrawing groups.

PMID- 20681686
TI  - Chiral bisguanidine-catalyzed inverse-electron-demand hetero-Diels-Alder reaction
      of chalcones with azlactones.
AB  - A new type of C(2)-symmetric chiral bisguanidine was designed as a highly
      efficient catalyst in the inverse-electron-demand hetero-Diels-Alder reaction of
      chalcones with azlactones for the first time. A wide variety of gamma,delta
      unsaturated delta-lactone derivatives with alpha-quaternary-beta-tertiary
      stereocenters were obtained in high yields (up to 88%) with excellent
      enantioselectivities (up to 99% ee). Hydrogen bonds were considered to be crucial
      for the activation and stereoinduction of the reaction. In all cases, the major
      was HDA adducts, which were obtained as a single diastereomer along with little
      amount of Michael addition products.

PMID- 20681687
TI  - Characterization of a six-coordinate ferrous high-spin heme with both
      intramolecular axial carboxylic acid and pyridine.
AB  - Synthesis of a bis-strapped porphyrin with a pyridyl residue on one side and a
      malonic acid on the other side gives after iron(II) insertion a six-coordinate
      complex in which both apical groups are the two axial ligands of the iron atom.
      Unexpectedly, this six-coordinate iron(II) complex proves to be high-spin, likely
      due to some stabilization of the axial metal-ligand antibonding orbitals.

PMID- 20681688
TI  - A new route to carbohydrate secondary and tertiary structure using Raman
      spectroscopy and Raman optical activity.
AB  - The structural characterization of carbohydrate polymers is important for
      understanding their functions and behavior. However, mainstream structural
      biology tools are not applicable to many carbohydrate polymers, particularly at
      physiological concentrations. We report Raman and Raman optical activity spectra
      of hyaluronan polymer, the hyaluronan tetramer building block, and the two
      monosaccharide components glucuronic acid and N-acetylglucosamine and identify
      marker bands corresponding to primary and secondary structure in
      glycosaminoglycans. Furthermore, we show that the hyaluronan polymer does not
      adopt tertiary structure under near-physiological conditions, confirming a
      proposed model of hyaluronan structural organization.

PMID- 20681689
TI  - Structure and orientation of water at charged lipid monolayer/water interfaces
      probed by heterodyne-detected vibrational sum frequency generation spectroscopy.
AB  - Cell membrane/water interfaces provide a unique environment for many biochemical
      reactions, and associated interfacial water is an integral part of such
      reactions. A molecular level understanding of the structure and orientation of
      water at lipid/water interfaces is required to realize the complex chemistry at
      biointerfaces. Here we report the heterodyne-detected vibrational sum frequency
      generation (HD-VSFG) studies of lipid monolayer/water interfaces. At charged
      lipid/water interfaces, the orientation of interfacial water is governed by the
      net charge on the lipid headgroup; at an anionic lipid/water interface, water is
      in the hydrogen-up orientation, and at the cationic lipid/water interface, water
      is in the hydrogen-down orientation. At the cationic and anionic lipid/water
      interfaces, interfacial water has comparable hydrogen bond strength, and it is
      analogous to the bulk water.

PMID- 20681690
TI  - Facile synthesis of aminodiborane and inorganic butane analogue NH3BH2NH2BH3.
AB  - A new ambient-temperature, catalyst-free reaction between ammonia borane and
      tetrahydrofuran borane produces aminodiborane via the formation of a dihydrogen
      bond and subsequent molecular hydrogen elimination. The facile synthesis of
      aminodiborane will make this long-sought active chemical reagent readily
      available for both inorganic and organic reactions. From aminodiborane, an
      inorganic butane analogue, NH(3)BH(2)NH(2)BH(3), was prepared, and its single
      crystal structure displayed a gauche rather than an anti form conformation.

PMID- 20681691
TI  - Tandem frustrated Lewis pair/tris(pentafluorophenyl)borane-catalyzed
      deoxygenative hydrosilylation of carbon dioxide.
AB  - The frustrated Lewis pair system consisting of 2 equiv of 2,2,6,6
      tetramethylpiperidine (TMP) and tris(pentafluorophenyl)borane [B(C(6)F(5))(3)]
      activates carbon dioxide to form a boratocarbamate-TMPH ion pair. In the presence
      of triethylsilane, this species is converted to a silyl carbamate and the known
      ion pair [TMPH](+)[HB(C(6)F(5))(3)](-), which recently was shown to react with
      CO(2) via transfer of the hydride from the hydridoborate to form the
      formatoborate [TMPH](+)[HC(O)OB(C(6)F(5))(3)](-). In the presence of extra
      B(C(6)F(5))(3) (0.1-1.0 equiv) and excess triethylsilane, the formatoborate is
      rapidly hydrosilated to form a formatosilane and regenerate
      [TMPH](+)[HB(C(6)F(5))(3)](-). The formatosilane in turn is rapidly hydrosilated
      by the B(C(6)F(5))(3)/Et(3)SiH system to CH(4), with (Et(3)Si)(2)O as the
      byproduct. At low [Et(3)SiH], intermediate CO(2) reduction products are observed;
      addition of more CO(2)/Et(3)SiH results in resumed hydrosilylation, indicating
      that this is a robust, living tandem catalytic system for the deoxygenative
      reduction of CO(2) to CH(4).

PMID- 20681692
TI  - 1,4,7-Trimethyloxatriquinane: S(N)2 reaction at tertiary carbon.
AB  - The synthesis of 1,4,7-trimethyloxatriquinane (1), a 3-fold tertiary alkyl
      oxonium salt, is described. Compound 1 is inert to solvolysis with alcohols, even
      at elevated temperatures, but undergoes facile substitution with the strongly
      nucleophilic azide anion. Since an S(N)1 pathway is excluded, the only reasonable
      mechanistic interpretation for the reaction between 1 and N(3)(-) is S(N)2,
      despite the fact that substitution is occurring at a tertiary carbon center. This
      finding is supported by computational modeling and a study of the reaction
      kinetics, and is also consistent with observed solvent and salt effects.

PMID- 20681693
TI  - Synthesis and characterization of a coupled binuclear Cu(I)/Cu(III) complex.
AB  - The synthesis through reaction of a C(alpha),C(ortho) dilithiated phosphazene
      with CuBr and structural characterization of the first example of a binuclear
      mixed valence [Cu(I)(N(2))/Cu(III)(C(4))] complex showing a metal-metal bond, as
      well as its applications in cyclopropanation and oxidation reactions, are
      described.

PMID- 20681694
TI  - Dioxygen activation by a non-heme iron(II) complex: formation of an iron(IV)-oxo
      complex via C-H activation by a putative iron(III)-superoxo species.
AB  - Iron(III)-superoxo intermediates are believed to play key roles in oxygenation
      reactions by non-heme iron enzymes. We now report that a non-heme iron(II)
      complex activates O(2) and generates its corresponding iron(IV)-oxo complex in
      the presence of substrates with weak C-H bonds (e.g., olefins and alkylaromatic
      compounds). We propose that a putative iron(III)-superoxo intermediate initiates
      the O(2)-activation chemistry by abstracting a H atom from the substrate, with
      subsequent generation of a high-valent iron(IV)-oxo intermediate from the
      resulting iron(III)-hydroperoxo species.

PMID- 20681695
TI  - Expanding micelle nanolithography to the self-assembly of multicomponent core
      shell nanoparticles.
AB  - Size, composition, and pattern formation are crucial elements in the fabrication
      of functional multicomponent nanoparticles (NPs). Self-assembly techniques
      provide relevant control over NP size distribution (down to a few nanometers in
      diameter), but more importantly, such techniques are amenable for practical
      applications since the resulting NPs (and arrays thereof) are programmed in the
      molecular structure of the precursors. Here, the diblock copolymer micelle
      nanolithography concept of achieving monodisperse NPs is extended to direct the
      synthesis of multicomponent core-shell NPs arranged in a triangular lattice.
      Special emphasis is set on Co(core)@Fe(shell) and corrosion resistant
      (FeCo)(core)@Au(shell) NPs. Electron microscopy analyses show a variety of core
      shell geometries spanning a wide range of oxide, metal, and alloy combinations.

PMID- 20681696
TI  - Iron-catalyzed Suzuki-Miyaura coupling of alkyl halides.
AB  - In the presence of novel iron(II) chloride-diphosphine complexes and magnesium
      bromide, lithium arylborates react with primary and secondary alkyl halides to
      give the corresponding coupling products in good to excellent yields. High
      functional group compatibility is also demonstrated in the reactions of
      substrates possessing reactive substituents, such as alkoxycarbonyl, cyano, and
      carbonyl groups.

PMID- 20681697
TI  - A carbene-carbene complex equilibrium.
AB  - Phenylchlorocarbene, generated by laser flash photolysis of
      phenylchlorodiazirine, formed highly stable pi-type complexes with 1,3,5
      trimethoxybenzene in pentane. The carbene and carbene complexes were in
      equilibrium. We measured the equilibrium constant (K = 1264 M(-1) at 294 K) and,
      from its temperature dependence, extracted the associated thermodynamic
      parameters: DeltaH(o) = -7.1 kcal/mol, DeltaS(o) = -10.2 eu, and DeltaG(o) = -4.1
      kcal/mol. The carbene complexes were characterized by UV-vis spectroscopy and
      computational analysis.

PMID- 20681698
TI  - Synthesis of a pH-sensitive nitrilotriacetic linker to peptide transduction
      domains to enable intracellular delivery of histidine imidazole ring-containing
      macromolecules.
AB  - Intracellular delivery of functional macromolecules using peptide transduction
      domains (PTDs) is an exciting technology with both experimental and therapeutic
      applications. Recent data indicate that PTD-mediated transduction occurs via
      fluid-phase macropinocytosis involving an intracellular pH drop to approximately
      5. Nitrilotriacetic acid (NTA)-coordinated metals avidly bind hexahistidine
      tagged macromolecules, including peptides and proteins. Histidine's imidazole
      ring has a pK(a) of 6, making this an attractive target for the biological pH
      drop of PTD-mediated macropinocytotic delivery. The objective of this study was
      to develop a pH-sensitive PTD delivery peptide (NTA(3)-PTD). We demonstrate the
      in vitro function of this novel peptide by delivering fluorescently labeled
      peptides (1.6 kDa) and functional enzymes, beta-galactosidase (119 kDa) and Cre
      recombinase (37 kDa). Furthermore, the NTA(3)-PTD peptide was able to deliver
      functional Cre recombinase in an in vivo mouse model.

PMID- 20681699
TI  - Noncovalent encapsulation stabilities in supramolecular nanoassemblies.
AB  - Exchange dynamics of lipophilic guest molecules, encapsulated in supramolecular
      nanoassemblies in aqueous solutions, have implications in evaluating the
      stability of drug delivery vehicles. This is because exchange dynamics is related
      to the propensity of a nanocarrier to be leaky. We describe a fluorescence
      resonance energy transfer (FRET) based method to evaluate guest exchange dynamics
      in the aqueous phase. We have utilized this method to analyze the stability of
      encapsulation in polymeric nanogels and other related amphiphilic nanoassemblies.

PMID- 20681700
TI  - Pd-catalyzed enantioselective allyl-allyl cross-coupling.
AB  - The Pd-catalyzed cross-coupling of allylic carbonates and allylB(pin) is
      described. The regioselectivity of this reaction is sensitive to the bite angle
      of the ligand, with small-bite-angle ligands favoring the branched substitution
      product. This mode of regioselection is consistent with a reaction that operates
      by a 3,3' reductive elimination reaction. In the presence of appropriate chiral
      ligands, this reaction is rendered enantioselective and applies to both aromatic
      and aliphatic allylic carbonates.

PMID- 20681701
TI  - Oxidation of organoplatinum(II) by coordinated dimethylsulfoxide: metal-metal
      bonded, dinuclear, liquid-crystalline complexes of platinum(III).
AB  - Reaction of [PtCl(2)(dmso)(2)] with 2,5-(dialkoxyphenyl)pyridine in HOAc leads to
      a dinuclear, acetate-bridged, metal-metal bonded complex of platinum(III); dmso
      in the presence of acid is found to be responsible for the oxidation. The dimer
      is analogous structurally to Pd(III) dimers implicated in catalytic
      acetoxylation. Platinum dimers with longer alkoxy chains are shown to be unique
      examples of liquid crystals of platinum(III).

PMID- 20681702
TI  - Investigation of the mechanism of C(sp3)-H bond cleavage in Pd(0)-catalyzed
      intramolecular alkane arylation adjacent to amides and sulfonamides.
AB  - The reactivity of C(sp(3))-H bonds adjacent to a nitrogen atom can be tuned to
      allow intramolecular alkane arylation under Pd(0) catalysis. Diminishing the
      Lewis basicity of the nitrogen lone pair is crucial for this catalytic activity.
      A range of N-methylamides and sulfonamides react exclusively at primary C(sp(3))
      H bonds to afford the products of alkane arylation in good yields. The isolation
      of a Pd(II) reaction intermediate has enabled an evaluation of the reaction
      mechanism with a focus on the role of the bases in the C(sp(3))-H bond cleaving
      step. The results of these stoichiometric studies, together with kinetic isotope
      effect experiments, provide rare experimental support for a concerted metalation
      deprotonation (CMD) transition state, which has previously been proposed in
      alkane C(sp(3))-H arylation. Moreover, DFT calculations have uncovered the
      additional role of the pivalate additive as a promoter of phosphine dissociation
      from the Pd(II) intermediate, enabling the CMD transition state. Finally, kinetic
      studies were performed, revealing the reaction rate expression and its
      relationship with the concentration of pivalate.

PMID- 20681703
TI  - Intramolecular palladium-catalyzed alkane C-H arylation from aryl chlorides.
AB  - The first examples of efficient and general palladium-catalyzed intramolecular
      C(sp(3))-H arylation of (hetero)aryl chlorides, giving rise to a variety of
      valuable cyclobutarenes, indanes, indolines, dihydrobenzofurans, and indanones,
      are described. The use of aryl and heteroaryl chlorides significantly improves
      the scope of C(sp(3))-H arylation by facilitating the preparation of reaction
      substrates. Careful optimization studies have shown that the palladium ligand and
      the base/solvent combination are crucial to obtaining the desired class of
      product in high yields. Overall, three sets of reaction conditions employing
      P(t)Bu(3), PCyp(3), or PCy(3) as the palladium ligand and K(2)CO(3)/DMF or
      Cs(2)CO(3)/pivalic acid/mesitylene as the base/solvent combination allowed five
      different classes of products to be accessed using this methodology. In total,
      more than 40 examples of C-H arylation have been performed successfully. When
      several types of C(sp(3))-H bond were present in the substrate, the arylation was
      found to occur regioselectively at primary C-H bonds vs secondary or tertiary
      positions. In addition, in the presence of several primary C-H bonds, selectivity
      trends correlate with the size of the palladacyclic intermediate, with five
      membered rings being favored over six- and seven-membered rings. Regio- and
      diastereoselectivity issues were studied computationally in the prototypal case
      of indane formation. DFT(B3PW91) calculations demonstrated that C-H activation is
      the rate-determining step and that the creation of a C-H agostic interaction,
      increasing the acidity of a geminal C-H bond, is a critical factor for the
      regiochemistry control.

PMID- 20681704
TI  - Crystal structure of chiral gammaPNA with complementary DNA strand: insights into
      the stability and specificity of recognition and conformational preorganization.
AB  - We have determined the structure of a PNA-DNA duplex to 1.7 A resolution by
      multiple-wavelength anomalous diffraction phasing method on a zinc derivative.
      This structure represents the first high-resolution 3D view of a hybrid duplex
      containing a contiguous chiral PNA strand with complete gamma-backbone
      modification ("gammaPNA"). Unlike the achiral counterpart, which adopts a random
      fold, this particular gammaPNA is already preorganized into a right-handed helix
      as a single strand. The new structure illustrates the unique characteristics of
      this modified PNA, possessing conformational flexibility while maintaining
      sufficient structural integrity to ultimately adopt the preferred P-helical
      conformation upon hybridization with DNA. The unusual structural adaptability
      found in the gammaPNA strand is crucial for enabling the accommodation of
      backbone modifications while constraining conformational states. In conjunction
      with NMR analysis characterizing the structures and substructures of the
      individual building blocks, these results provide unprecedented insights into how
      this new class of chiral gammaPNA is preorganized and stabilized, before and
      after hybridization with a cDNA strand. Such knowledge is crucial for the future
      design and development of PNA for applications in biology, biotechnology, and
      medicine.

PMID- 20681705
TI  - The histidine effect. Electron transfer and capture cause different dissociations
      and rearrangements of histidine peptide cation-radicals.
AB  - Electron-transfer and -capture dissociations of doubly protonated peptides gave
      dramatically different product ions for a series of histidine-containing
      pentapeptides of both non-tryptic (AAHAL, AHAAL, AHADL, AHDAL) and tryptic
      (AAAHK, AAHAK, AHAAK, HAAAK, AAAHR, AAHAR, AHAAR, HAAAR) type. Electron transfer
      from gaseous Cs atoms and fluoranthene anions triggered backbone dissociations of
      all four N-C(alpha) bonds in the peptide ions in addition to loss of H and NH(3).
      Substantial fractions of charge-reduced cation-radicals did not dissociate on an
      experimental time scale ranging from 10(-6) to 10(-1) s. Multistage tandem mass
      spectrometric (MS(n)) experiments indicated that the non-dissociating cation
      radicals had undergone rearrangements. These were explained as being due to
      proton migrations from N-terminal ammonium and COOH groups to the C-2' position
      of the reduced His ring, resulting in substantial radical stabilization. Ab
      initio calculations revealed that the charge-reduced cation-radicals can exist as
      low-energy zwitterionic amide pi* states which were local energy minima. These
      states underwent facile exothermic proton migrations to form aminoketyl radical
      intermediates, whereas direct N-C(alpha) bond cleavage in zwitterions was
      disfavored. RRKM analysis indicated that backbone N-C(alpha) bond cleavages did
      not occur competitively from a single charge-reduced precursor. Rather, these
      bond cleavages proceeded from distinct intermediates which originated from
      different electronic states accessed by electron transfer. In stark contrast to
      electron transfer, capture of a free electron by the peptide ions mainly induced
      radical dissociations of the charge-carrying side chains and loss of a hydrogen
      atom followed by standard backbone dissociations of even-electron ions. The
      differences in dissociation are explained by different electronic states being
      accessed upon electron transfer and capture.

PMID- 20681706
TI  - Azodicarboxamides as template binding motifs for the building of hydrogen-bonded
      molecular shuttles.
AB  - Azodicarboxamides (R(2)NCON=NCONR(2)) are shown to act as new templates for the
      assembly of unprecedented azo-functionalized hydrogen-bond-assembled
      [2]rotaxanes. Moreover, these binding sites can be reversibly and efficiently
      interconverted with their hydrazo forms through a hydrogenation-dehydrogenation
      strategy of the nitrogen-nitrogen bond. This novel chemically switchable control
      element has been implemented in stimuli-responsive molecular shuttles that work
      through a reversible azo/hydrazo interconversion, producing large amplitude net
      positional changes with a good discrimination between the binding sites of the
      macrocycle in both states of the shuttle. These molecular shuttles are able to
      operate by two different mechanisms: in a discrete mode through two reversible
      and independent chemical events and, importantly, in a continuous regime through
      a catalyzed ester bond formation reaction in which the shuttle acts as an
      organocatalyst. In this latter, the incorporation of both states of the shuttle
      into this simple chemical reaction network promotes a dynamic translocation of
      the macrocycle between two nitrogen and carbon-based stations of the thread
      allowing an energetically uphill esterification process to take place.

PMID- 20681707
TI  - CO2 triggering and controlling orthogonally multiresponsive photochromic systems.
AB  - We report a new generic method of reversibly controlling the photochromism of
      spiropyrans. It was found that the photochromic effect of spiropyrans can be
      reversibly switched on and off by addition and removal of carbon dioxide (CO(2))
      to spiropyran in alcohol solutions containing an amidine (i.e., DBU) that acts as
      a CO(2) sensitizer. Spiropyrans are not photochromic in the presence of DBU but
      photochromic when CO(2) is subsequently added to the solution. The CO(2) is
      readily removed by inert gas bubbling, thus allowing facile activation and
      deactivation of the photochromic effect. Carbon dioxide, without the presence of
      the sensitizing amidine, had no effect on photochromism of the spiropyrans. Other
      photochromic dyes classes such as spirooxazines and chromenes are not affected by
      this CO(2)/DBU stimulus. As a result, orthogonal activation of mixtures of
      spirooxazines and spiropyrans was achieved to provide four color states (clear,
      yellow, green, and blue) by varying the combinations of the stimuli of UV,
      visible light, CO(2), and CO(2) depleted. This finding now permits the many
      applications using spiropyrans to be CO(2) responsive.

PMID- 20681708
TI  - Structural and chemical control in assembly of multicomponent metal-organic
      coordination networks on a surface.
AB  - Surface-supported supramolecular self-assembly has been used to generate
      multicomponent two-dimensional metal-organic coordination networks on a Au(111)
      surface. The networks consist of linker ligands of 4',4''''-(1,4
      phenylene)bis(2,2':6',2''-terpyridine) and nodal ligands of 5,10,15,20-tetra(4
      pyridyl)porphyrin that are connected by pyridine-Fe-terpyridine motifs. Scanning
      tunneling microscopy revealed the coexistence of two polymorphic types of network
      structures (rhombus and Kagome). Through control of the dosage of the constituent
      ligands, homogeneous structural phases were obtained selectively. In particular,
      the rhombus structure could be converted into the more complex and more open
      Kagome structure by inclusion of guest molecules. Finally, coordination networks
      providing structural and chemical homogeneity were realized by judiciously
      choosing the dosages of the constituent ligands and the chemical substitution of
      the porphyrin ligands.

PMID- 20681709
TI  - Engineering ESPT pathways based on structural analysis of LSSmKate red
      fluorescent proteins with large Stokes shift.
AB  - LSSmKate1 and LSSmKate2 are monomeric red fluorescent proteins (RFPs) with large
      Stokes shifts (LSSs), which allows for efficient separation of absorbance and
      emission maxima, as well as for excitation with conventional two-photon laser
      sources. These LSSmKates differ by a single amino acid substitution at position
      160 and exhibit absorbance maxima around 460 nm, corresponding to a neutral DsRed
      like chromophore. However, excitation at 460 nm leads to fluorescence emission
      above 600 nm. Structures of LSSmKate1 and LSSmKate2, determined at resolutions of
      2.0 and 1.5 A, respectively, revealed that the predominant DsRed-chromophore
      configurations are cis for LSSmKate1 but trans for LSSmKate2. Crystallographic
      and mutagenesis analyses, as well as isotope and temperature dependences, suggest
      that an excited-state proton transfer (ESPT) is responsible for the LSSs observed
      in LSSmKates. Hydrogen bonding between the chromophore hydroxyl and Glu160 in
      LSSmKate1 and a proton relay involving the chromophore tyrosine hydroxyl, Ser158,
      and the Asp160 carboxylate in LSSmKate2 represent the putative ESPT pathways.
      Comparisons with mKeima LSS RFP suggest that similar proton relays could be
      engineered in other FPs. Accordingly, we mutated positions 158 and 160 in several
      conventional red-shifted FPs, including mNeptune, mCherry, mStrawberry, mOrange,
      and mKO, and the resulting FP variants exhibited LSS fluorescence emission in a
      wide range of wavelengths from 560 to 640 nm. These data suggest that different
      chromophores formed by distinct tripeptides in different environments can be
      rationally modified to yield RFPs with novel photochemical properties.

PMID- 20681710
TI  - Synthesis, morphological control, and antibacterial properties of hollow/solid
      Ag2S/Ag heterodimers.
AB  - Ag(2)S and Ag are important functional materials that have received considerable
      research interest in recent years. In this work, we develop a solution-based
      synthetic method to combine these two materials into hollow/solid Ag(2)S/Ag
      heterodimers at room temperature. Starting from monodisperse Cu(2)O solid
      spheres, CuS hollow spheres can be converted from Cu(2)O through a modified
      Kirkendall process, and the obtained CuS can then be used as a solid precursor
      for preparation of the Ag(2)S/Ag heterodimers through ion exchange and photo
      assisted reduction. We have found that formation of the Ag(2)S/Ag heterodimers is
      instantaneous, and the size of Ag nanocrystals on the hollow spheres of Ag(2)S
      can be controlled by changing the concentration and power of reducing agents in
      the synthesis. The growth of Ag nanoparticles on hollow spheres of Ag(2)S in the
      dimers is along the [111] direction of the silver crystal; the light absorption
      properties have also been investigated. Furthermore, coupling or tripling of
      Ag(2)S/Ag heterodimers into dumbbell-like trimers ((Ag(2)S)(2)/Ag, linear) and
      triangular tetramers ((Ag(2)S)(3)/Ag, coplanar) can also be attained at 60
      degrees C by adding the bidentate ligand ethylenediamine as a cross-linking
      agent. To test the applicability of this highly asymmetric dipolar composite,
      photocatalytic inactivation of Escherichia coli K-12 in the presence of the as
      prepared Ag(2)S/Ag heterodimers has been carried out under UV irradiation. The
      added Ag(2)S/Ag heterodimers show good chemical stability under prolonged UV
      irradiation, and no appreciable solid dissolution is found. Possible mechanisms
      regarding the enhanced antibacterial activity have also been addressed.

PMID- 20681711
TI  - Pairing fullerenes and porphyrins: supramolecular wires that exhibit charge
      transfer activity.
AB  - A concept is elaborated of pairing electron donors and electron acceptors that
      share a common trait, wire-like features, as a powerful means to realize a new
      and versatile class of electron donor-acceptor nanohybrids. Important variables
      are fine-tuning (i) the complexation strength, (ii) the electron/energy transfer
      behavior, and (iii) the solubilities of the resulting architectures. In
      particular, a series of supramolecular porphyrin/fullerene hybrids assembled by
      the hydrogen bonding of Hamilton receptor/cyanuric acid motif has been realized.
      Putting the aforementioned variables into action, the association constants
      (K(ass)), as they were determined from (1)H NMR and steady-state fluorescence
      assays, were successfully tweaked with values in the range of 10(4)-10(5) M(-1).
      In fact, our detailed studies corroborate that the latter reveal a dependence on
      the nature of the spacer, that is, p-phenylene-ethynylene, p-phenylene-vinylene,
      p-ethynylene, and fluorene, as well as on the length of the spacer. Complementary
      performed transient absorption studies confirm that electron transfer is indeed
      the modus operandi in our novel class of electron donor-acceptor nanohybrids,
      while energy transfer plays, if any, only a minor role. The accordingly formed
      electron transfer products, that is, one-electron oxidized porphyrins and one
      electron reduced fullerenes, are long-lived with lifetimes that reach well into
      the time domain of tens of nanoseconds. Finally, we have used the distance
      dependence on electron transfer, charge separation and charge recombination, to
      determine for the first time a beta value (0.11 A(-1)) for hydrogen-bonding
      mediated electron transfer.

PMID- 20681712
TI  - Tetrathiafulvalene end-functionalized poly(N-isopropylacrylamide): a new class of
      amphiphilic polymer for the creation of multistimuli responsive micelles.
AB  - In this article, we report the formation of micelles from a tetrathiafulvalene
      (TTF) end-functionalized poly(N-isopropylacrylamide) (poly(NIPAM)) derivative
      (1). We have determined the critical aggregation concentration (CAC) and average
      diameter of the micelles using fluorescence spectroscopy and dynamic light
      scattering experiments, respectively. We have exploited the NIPAM backbone of the
      polymer to thermally transform the swollen hydrophilic poly(NIPAM) derivative to
      a more globular hydrophobic state at the lower critical solution temperature
      (LCST). Finally, we have shown that we can exploit the chemical oxidation and
      complexation properties of the TTF unit to disrupt the micelle architecture to
      release the hydrophobic dye Nile Red from the interior of the micelle.

PMID- 20681713
TI  - Oxygen-17 appears only in protein in water-stressed soybean leaves labeled by
      (17)O2.
AB  - We have used a rotational-echo adiabatic-passage double-resonance (13)C{(17)O}
      solid-state NMR experiment to prove that the glycine produced in the oxygenase
      reaction of ribulose bisphosphate carboxylase-oxygenase is incorporated
      exclusively into protein (or protein precursors) of intact, water-stressed
      soybean leaves exposed to (13)CO(2) and (17)O(2). The water stress increased
      stomatal resistance and decreased gas exchange so that the Calvin cycle in the
      leaf chloroplasts was no more than 35% (13)C isotopically enriched. Labeled O(2)
      levels were sufficient, however, to increase the (17)O isotopic concentration of
      oxygenase products 20-fold over the natural-abundance level of 0.04%. The
      observed direct incorporation of glycine into protein shows that water stress
      suppresses photorespiration in soybean leaves.

PMID- 20681714
TI  - Molecular impact of the membrane potential on the regulatory mechanism of proton
      transfer in sensory rhodopsin II.
AB  - Metabolism establishes a potential difference across the cell membrane of every
      living cell which drives and regulates secondary ion and solute transfer across
      membrane proteins. Unraveling the effect of the membrane potential on the level
      of single molecular groups of the membrane protein was long hampered by the lack
      of appropriate analytical techniques. We have developed Surface Enhanced Infrared
      Difference Absorption Spectroscopy (SEIDAS), a highly sensitive vibrational
      technique for surface analysis, for the study of solid-supported monolayers of
      orientated membrane proteins. Here, we present spectroscopic data on vibrational
      changes of sensory rhodopsin II from Natronomonas pharaonis (NpSR II). The
      application of the electrode potential provides a voltage drop across the NpSR II
      monolayer through the Helmholtz double layer that mimics the cellular membrane
      potential. IR difference spectra indicated a shift of the photostationary
      equilibrium from an M and O mixture toward an M dominant equilibrium. The shift
      of positive to negative potential exhibited similar effects on the light-induced
      SEIDA spectra as the increase in pH. This effect is explained in terms of local
      pH change raised by the compensation of excess charge from the electrode. As we
      have shown earlier (Jiang, et al. Proc. Natl. Acad. Sci. U.S.A. 2008, 105 (34),
      12113-12117), the application of an electric field opposite to the physiological
      proton transfer from the retinal Schiff base to its counterion Asp75 leads to the
      selective halt of the latter. However, when the solution pH is much higher than
      5.8, that is, when the proton releasing group at the extracellular side is
      ionized, proton transfer of Asp75 becomes insensitive to the electric field
      exerted by the electrode. We infer that the deprotonation of the proton release
      group creates a local polar environment surrounding Asp75 as a consequence of
      hydrogen-bonding rearrangements that exceeds the energy of the external dipole.
      Our results reveal a molecular model for the physiological regulation of the
      photocycle of NpSR II by the potential drop across the membrane which came about
      by the interplay between the change in local pH at the membrane surface and the
      external electric field.

PMID- 20681716
TI  - Largest molecular clusters in the supertetrahedral Tn series.
AB  - Supertetrahedral Tn clusters are exact fragments of cubic ZnS-type lattice and
      are often formed in situ as building units for the construction of 3-D open
      framework chalcogenide materials. Small Tn clusters can also be synthesized in
      discrete forms, allowing them to exist as soluble species in solution. In
      addition to their tunable electronic and optical properties, these soluble
      clusters can be used as precursors for the synthesis of porous semiconducting and
      optical materials. However, the synthesis of large Tn clusters is a significant
      challenge, and for several decades prior to this work, the size of the discrete
      Tn cluster remained at T3, with only 10 metal sites (e.g.,
      [Cd(10)S(4)(SPh)(16)](4-) and [M(5)Sn(5)S(20)](10-), M = Zn, Co). Here we report
      a family of discrete chalcogenide T4 clusters ([M(x)Ga(18-x)Sn(2)Q(35)](12-), x =
      2 or 4; M = Mn, Cu, Zn; Q = S, Se) whose discovery resulted from an unusual phase
      transformation from a 3-D T4 covalent framework into 0-D T4 molecular clusters.
      The driving force for such a transformation is the perfect match in both charge
      density and geometry between chalcogenide clusters and protonated amine, leading
      to the higher stability of isolated clusters. The perfect match is achieved by
      using complex quaternary compositions to maximize charge tunability of the
      cluster. These T4 clusters are the largest molecular Tn clusters known to date
      and can be made in various compositions showing tunable band structures in both
      solution and solid state.

PMID- 20681715
TI  - Single-molecule observation of protein adsorption onto an inorganic surface.
AB  - Understanding the interactions between silicon-based materials and proteins from
      the bloodstream is of key importance in a myriad of realms, such as the design of
      nanofluidic devices and functional biomaterials, biosensors, and biomedical
      molecular diagnosis. By using nanopores fabricated in 20 nm-thin silicon nitride
      membranes and highly sensitive electrical recordings, we show single-molecule
      observation of nonspecific protein adsorption onto an inorganic surface. A
      transmembrane potential was applied across a single nanopore-containing membrane
      immersed into an electrolyte-filled chamber. Through the current fluctuations
      measured across the nanopore, we detected long-lived captures of bovine serum
      albumin (BSA), a major multifunctional protein present in the circulatory system.
      Based upon single-molecule electrical signatures observed in this work, we judge
      that the bindings of BSA to the nitride surface occurred in two distinct
      orientations. With some adaptation and further experimentation, this approach,
      applied on a parallel array of synthetic nanopores, holds potential for use in
      methodical quantitative studies of protein adsorption onto inorganic surfaces.

PMID- 20681717
TI  - Investigation of methanol oxidation over Au/catalysts using operando IR
      spectroscopy: determination of the active sites, intermediate/spectator species,
      and reaction mechanism.
AB  - FTIR spectroscopy coupled with mass spectrometry has been used to study the
      mechanism of methanol oxidation at low temperatures on nanostructured Au/CeO(2)
      and Au/TiO(2) catalysts. Activity and selectivity toward CO(2) have been
      investigated through simultaneous analysis of adsorbed surface species and
      gaseous species, and some key steps in the oxidation pathway, active sites, and
      intermediate species are proposed. Among the detected species, some kinds of
      methoxy species formed on the support were identified as intermediates, which
      further transform into formates whose oxidation was found to be the rate
      determining step for the reaction. The role of the support and the noble metal in
      the mechanism are revealed using operando spectroscopy.

PMID- 20681718
TI  - A combined experimental and theoretical study of ion solvation in liquid N
      methylacetamide.
AB  - Most current biomolecular simulations are based on potential energy functions
      that treat the electrostatic energy as a sum of pairwise Coulombic interactions
      between effective fixed atomic charges. This approximation, in which many-body
      induced polarization effects are included in an average way, is expected to be
      satisfactory for a wide range of systems, but less accurate for processes
      involving the transfer and partition of ions among heterogeneous environments.
      The limitations of these potential energy functions are perhaps most obvious in
      studies of ion permeation through membrane channels. In many cases, the pore is
      so narrow that the permeating ion must shed most of its surrounding water
      molecules and the large energetic loss due to dehydration must be compensated by
      coordination with protein atoms. Interactions of cations with protein backbone
      carbonyl oxygens, in particular, play a critical role in several important
      biological channels. As a first step toward meeting the challenge of developing
      an accurate explicit accounting for induced polarization effects, the present
      work combines experiments and computation to characterize the interactions of
      alkali and halide ions with N-methylacetamide chosen to represent the peptide
      bond. From solubility measurements, we extract the solvation free energies of KCl
      and NaCl in liquid N-methylacetamide. Polarizable models based on the Drude
      oscillator are then developed and compared with available experimental and ab
      initio data. The good agreement for a range of structural and thermodynamic
      properties in the gas and condensed phases suggests that the polarizable models
      provide an accurate representation of ion-amide interactions in biological
      systems.

PMID- 20681719
TI  - The aberrance of the 4S diastereomer of 4-hydroxyproline.
AB  - Prolyl 4-hydroxylases install a hydroxyl group in the 4R configuration on the
      gamma-carbon atom of certain (2S)-proline (Pro) residues in tropocollagen,
      elastin, and other proteins to form (2S,4R)-4-hydroxyproline (Hyp). The gauche
      effect arising from this prevalent post-translational modification enforces a
      C(gamma)-exo ring pucker and stabilizes the collagen triple helix. The Hyp
      diastereomer (2S,4S)-4-hydroxyproline (hyp) has not been observed in a protein,
      despite the ability of electronegative 4S substituents to enforce the more common
      C(gamma)-endo ring pucker of Pro. Here, we use density functional theory,
      spectroscopy, crystallography, and calorimetry to explore the consequences of hyp
      incorporation on protein stability using a collagen model system. We find that
      the 4S-hydroxylation of Pro to form hyp does indeed enforce a C(gamma)-endo ring
      pucker but a transannular hydrogen bond between the hydroxyl moiety and the
      carbonyl of hyp distorts the main-chain torsion angles that typically accompany a
      C(gamma)-endo ring pucker. This same transannular hydrogen bond enhances an n-
      >pi* interaction that stabilizes the trans conformation of the peptide bond
      preceding hyp, endowing hyp with the unusual combination of a C(gamma)-endo ring
      pucker and high trans/cis ratio. O-Methylation of hyp to form (2S,4S)-4
      methoxyproline (mop) eliminates the transannular hydrogen bond and restores a
      prototypical C(gamma)-endo pucker. mop residues endow the collagen triple helix
      with much more conformational stability than do hyp residues. These findings
      highlight the critical importance of the configuration of the hydroxyl group
      installed on C(gamma) of proline residues.

PMID- 20681720
TI  - The impact of hydrogen bonding on amide 1H chemical shift anisotropy studied by
      cross-correlated relaxation and liquid crystal NMR spectroscopy.
AB  - Site-specific (1)H chemical shift anisotropy (CSA) tensors have been derived for
      the well-ordered backbone amide moieties in the B3 domain of protein G (GB3).
      Experimental input data include residual chemical shift anisotropy (RCSA),
      measured in six mutants that align differently relative to the static magnetic
      field when dissolved in a liquid crystalline Pf1 suspension, and cross-correlated
      relaxation rates between the (1)H(N) CSA tensor and either the (1)H-(15)N, the
      (1)H-(13)C', or the (1)H-(13)C(alpha) dipolar interactions. Analyses with the
      assumption that the (1)H(N) CSA tensor is symmetric with respect to the peptide
      plane (three-parameter fit) or without this premise (five-parameter fit) yield
      very similar results, confirming the robustness of the experimental input data,
      and that, to a good approximation, one of the principal components orients
      orthogonal to the peptide plane. (1)H(N) CSA tensors are found to deviate
      strongly from axial symmetry, with the most shielded tensor component roughly
      parallel to the N-H vector, and the least shielded component orthogonal to the
      peptide plane. DFT calculations on pairs of N-methyl acetamide and acetamide in H
      bonded geometries taken from the GB3 X-ray structure correlate with experimental
      data and indicate that H-bonding effects dominate variations in the (1)H(N) CSA.
      Using experimentally derived (1)H(N) CSA tensors, the optimal relaxation
      interference effect needed for narrowest (1)H(N) TROSY line widths is found at
      approximately 1200 MHz.

PMID- 20681721
TI  - Simultaneous discrimination of handedness and diameter of single-walled carbon
      nanotubes (SWNTs) with chiral diporphyrin nanotweezers leading to enrichment of a
      single enantiomer of (6,5)-SWNTs.
AB  - Separation of single-walled carbon nanotubes (SWNTs) according to their
      handedness has been attracting growing interest. Our methodology to separate the
      enantiomers of SWNTs is based on molecular recognition with chiral diporphyrin
      nanotweezers. Herein, we report novel nanotweezers 1 consisting of two chiral
      porphyrins and phenanthrene in between. These nanotweezers 1 are rationally
      designed to discriminate diameter and handedness simultaneously by taking into
      account the relationship between the (n, m) selectivity and the structures of
      previously reported chiral nanotweezers. Owing to the relatively narrow cleft
      made by two porphyrins, the nanotweezers 1 showed high selectivity toward (6,5)
      SWNTs possessing the smallest diameter among the major components of CoMoCAT
      SWNTs. In addition, the chiral diporphyrin 1 discriminated the left- and right
      handed structures of (6,5)-SWNTs, providing high enantiomeric excess (67% ee on
      the basis of the (6,5)-SWNTs with high optical purity recently reported by
      Weisman). In conclusion, only the single stereoisomer of (6,5)-SWNTs was highly
      enriched through the extraction of CoMoCAT-SWNTs with phenanthrene-bridged chiral
      diporphyrin nanotweezers 1.

PMID- 20681722
TI  - Self-assembly and induced circular dichroism in dendritic supramolecules with
      cholesteric pendant groups.
AB  - We report on the solid-state structural features of self-assembled chiral
      supramolecules based on ionic complexation of chiral cholesteric pendant groups
      with achiral dendritic macromolecules and show that their optical activity
      exhibits a systematic change in the ultraviolet/visible light (UV-vis) absorption
      and enhancement in the circular dichroism (CD) signal, indicating the occurrence
      of supramolecular chirality, also referred to as induced circular dichroism
      (ICD). We construct a homologous series of complexes by varying systematically
      from 1 to 3 the generation of dendritic units contained in dendrons, dendrimers,
      and dendronized polymers. The structural properties of the complexes are
      investigated by means of small-angle X-ray scattering (SAXS) and transmission
      electron microscopy (TEM). Depending on the class of dendritic molecule and the
      generation, lamellar, columnar hexagonal, oblique columnar, and rectangular
      columnar phases can be found, with a direct correlation among the degrees of
      freedom of the dendritic macromolecules used and the level of order achieved in
      the self-assembled solid-state structures. The enhancement of the optical signals
      of these mesoscopic structures appears to be correlated with their order in the
      solid state. Complexes with the longest lattice correlation lengths also show the
      most enhanced CD signals. These results show the unique versatility of dendritic
      macromolecules as supramolecular templates capable of organizing low molecular
      weight chiral pendant units into a variety of solid-state structures with
      amplified optical properties.

PMID- 20681723
TI  - 'Carbene radicals' in Co(II)(por)-catalyzed olefin cyclopropanation.
AB  - The mechanism of cobalt(II)-porphyrin-mediated cyclopropanation of olefins with
      diazoesters was studied. The first step--reaction of cobalt(II)-porphyrin with
      ethyl diazoacetate (EDA)--was examined using EPR and ESI-MS techniques. EDA
      reacts with cobalt(II)-porphyrin to form a 1:1 Co(por)(CHCOOEt) adduct that
      exists as two isomers: the 'bridging carbene' C' in which the 'carbene' is bound
      to the metal and the pyrrolic nitrogen of the porphyrin that has a d(7)
      configuration on the metal, and the 'terminal carbene' C in which the 'carbene'
      behaves as a redox noninnocent ligand having a d(6) cobalt center and the
      unpaired electron residing on the 'carbene' carbon atom. The subsequent
      reactivities of the thus formed 'cobalt carbene radical' with propene, styrene,
      and methyl acrylate were studied using DFT calculations. The calculations suggest
      that the formation of the carbene is the rate-limiting step for the
      unfunctionalized Co(II)(por) and that the cyclopropane ring formation proceeds
      via a stepwise radical process: Radical addition of the 'carbene radical' C to
      the C=C double bonds of the olefins results in formation of the gamma-alkyl
      radical intermediates D. Species D then easily collapse in almost barrierless
      ring-closure reactions (TS3) to form the cyclopropanes. This radical mechanism
      readily explains the high activity of Co(II)(por) species in the cyclopropanation
      of electron-deficient olefins such as methyl acrylate.

PMID- 20681724
TI  - Structure-activity relationships in gold nanoparticle dimers and trimers for
      surface-enhanced Raman spectroscopy.
AB  - Understanding the detailed relationship between nanoparticle structure and
      activity remains a significant challenge for the field of surface-enhanced Raman
      spectroscopy. To this end, the structural and optical properties of individual
      plasmonic nanoantennas comprised of Au nanoparticle assemblies that are coated
      with organic reporter molecules and encapsulated by a SiO(2) shell have been
      determined using correlated transmission electron microscopy (TEM), dark-field
      Rayleigh scattering microscopy, surface-enhanced Raman scattering (SERS)
      microscopy, and finite element method (FEM) calculations. The distribution of
      SERS enhancement factors (EFs) for a structurally and optically diverse set of
      nanoantennas is remarkably narrow. For a collection of 30 individual nanoantennas
      ranging from dimers to heptamers, the EFs vary by less than 2 orders of
      magnitude. Furthermore, the EFs for the hot-spot-containing nanoparticles are
      uncorrelated to aggregation state and localized surface plasmon resonance (LSPR)
      wavelength but are crucially dependent on the size of the interparticle gap. This
      study demonstrates that the creation of hot spots, where two particles are in
      subnanometer proximity or have coalesced to form crevices, is paramount to
      achieving maximum SERS enhancements.

PMID- 20681725
TI  - Dynamics characterization of fully hydrated bacterial cell walls by solid-state
      NMR: evidence for cooperative binding of metal ions.
AB  - The bacterial cell wall maintains a cell's integrity while allowing growth and
      division. It is made up of peptidoglycan (PG), a biopolymer forming a
      multigigadalton bag-like structure, and, additionally in gram-positive bacteria,
      of covalently linked anionic polymers collectively called teichoic acids. These
      anionic polymers are thought to play important roles in host-cell adhesion,
      inflammation, and immune activation. In this Article, we compare the flexibility
      and the organization of peptidoglycans from gram-negative bacteria (E. coli) with
      its counterpart from different gram-positive bacteria using solid-state nuclear
      magnetic resonance spectroscopy (NMR) under magic-angle sample spinning (MAS).
      The NMR fingerprints suggest an identical local conformation of the PG in all of
      these bacterial species. Dynamics in the peptidoglycan network decreases from E.
      coli to B. subtilis and from B. subtilis to S. aureus and correlates mainly with
      the degree of peptide cross-linkage. For intact bacterial cells and isolated cell
      walls, we show that (31)P solid-state NMR is particularly well adapted to
      characterize and differentiate wall teichoic acids of different species. We have
      further observed complexation with divalent ions, highlighting an important
      structural aspect of gram-positive cell wall architecture. We propose a new model
      for the interaction of divalent cations with both wall teichoic acids and
      carbonyl groups of peptidoglycan.

PMID- 20681726
TI  - New insights into poly(lactic-co-glycolic acid) microstructure: using repeating
      sequence copolymers to decipher complex NMR and thermal behavior.
AB  - Sequence, which Nature uses to spectacular advantage, has not been fully
      exploited in synthetic copolymers. To investigate the effect of sequence and
      stereosequence on the physical properties of copolymers, a family of complex
      isotactic, syndiotactic, and atactic repeating sequence poly(lactic-co-glycolic
      acid) copolymers (RSC PLGAs) were prepared and their NMR and thermal behavior was
      studied. The unique suitability of polymers prepared from the bioassimilable
      lactic and glycolic acid monomers for biomedical applications makes them ideal
      candidates for this type of sequence engineering. Polymers with repeating units
      of LG, GLG and LLG (L = lactic, G = glycolic) with controlled and varied
      tacticities were synthesized by assembly of sequence-specific, stereopure
      dimeric, trimeric, and hexameric segmer units. Specifically labeled deuterated
      lactic and glycolic acid segmers were likewise prepared and polymerized.
      Molecular weights for the copolymers were in the range M(n) = 12-40 kDa by size
      exclusion chromatography in THF. Although the effects of sequence-influenced
      solution conformation were visible in all resonances of the (1)H and (13)C NMR
      spectra, the diastereotopic methylene resonances in the (1)H NMR (CDCl(3)) for
      the glycolic units of the copolymers proved most sensitive. An octad level of
      resolution, which corresponds to an astounding 31-atom distance between the most
      separated stereocenters, was observed in some mixed sequence polymers.
      Importantly, the level of sensitivity of a particular NMR resonance to small
      differences in sequence was found to depend on the sequence itself. Thermal
      properties were also correlated with sequence.

PMID- 20681727
TI  - XeOF3(-), an example of an AX3YE2 valence shell electron pair repulsion
      arrangement; syntheses and structural characterizations of [M][XeOF3] (M = Cs,
      N(CH3)4).
AB  - The XeOF(3)(-) anion has been synthesized as its Cs(+) and N(CH(3))(4)(+) salts
      and structurally characterized in the solid state by low-temperature Raman
      spectroscopy and quantum-chemical calculations. Vibrational frequency assignments
      for [Cs][XeOF(3)] and [N(CH(3))(4)][XeOF(3)] were aided by (18)O enrichment. The
      calculated anion geometry is based on a square planar AX(3)YE(2) valence-shell
      electron-pair repulsion arrangement with the longest Xe-F bond trans to the
      oxygen atom. The F-Xe-F angle is bent away from the oxygen atom to accommodate
      the greater spatial requirement of the oxygen double bond domain. The
      experimental vibrational frequencies and trends in their isotopic shifts are
      reproduced by the calculated gas-phase frequencies at several levels of theory.
      The XeOF(3)(-) anion of the Cs(+) salt is fluorine-bridged in the solid state,
      whereas the anion of the N(CH(3))(4)(+) salt has been shown to best approximate
      the gas-phase anion. Although [Cs][XeOF(3)] and [N(CH(3))(4)][XeOF(3)] are shock
      sensitive explosives, the decomposition pathways for the anions have been
      inferred from their decomposition products at 20 degrees C. The latter consist of
      XeF(2), [Cs][XeO(2)F(3)], and [N(CH(3))(4)][F]. Enthalpies and Gibbs free
      energies of reaction obtained from Born-Fajans-Haber thermochemical cycles
      support the proposed decomposition pathways and show that both disproportionation
      to XeF(2), [Cs][XeO(2)F(3)], and CsF and reduction to XeF(2), CsF, and O(2) are
      favorable for [Cs][XeOF(3)], while only reduction to XeF(2) accompanied by
      [N(CH(3))(4)][F] and O(2) formation are favorable for [N(CH(3))(4)][XeOF(3)]. In
      all cases, the decomposition pathways are dominated by the lattice enthalpies of
      the products.

PMID- 20681728
TI  - Electrochemical behavior and electrogenerated chemiluminescence of star-shaped D
      A compounds with a 1,3,5-triazine core and substituted fluorene arms.
AB  - We report the synthesis, electrochemistry, and electrogenerated chemiluminescence
      of a series of star-shaped donor-acceptor (D-A) molecules. The star-shaped
      molecules consist of an electron-deficient 1,3,5-triazine core with three
      fluorene arms substituted with diarylamino (TAM1-TAM3) or carbazolyl (TAM4)
      electron donors. Cyclic voltammetry of TAM1-TAM3 shows that the reduction
      consists of one wave of single electron transfer to the core, while the oxidation
      exhibits a single peak of three sequential electron-transfer processes, with the
      formation of a trication. The carbazole-containing molecule TAM4 after oxidation
      undergoes a subsequent rapid chemical reaction to produce a dimer (via the
      overall coupling of two radical cations with the loss of two protons). The dimer
      electrooxidizes more easily than the monomer of TAM4. With continuous cycling on
      the oxidation side, a conductive polymer film is formed on the surface of the
      working electrode. Because of the presence of the acceptor (triazine) center and
      strong donors in the arms (diarylamine or carbazole), TAM1-TAM3 exhibit large
      solvatochromic effects with emissions ranging from deep blue (428 nm) to orange
      red (575 nm) depending on the solvent polarity. These star-shaped molecules show
      high PL quantum yields of 0.70-0.81. The electrogenerated chemiluminescence (ECL)
      of TAM1-TAM3 in nonaqueous solutions showed strong ECL that could be seen with
      the naked eye in a well-lit room. Because the enthalpy of annihilation is higher
      than the energy required for formation of the singlet excited state, the ECL
      emission is believed to be generated via S-route annihilation. However, TAM4
      shows weak annihilation ECL because of the production of polymer film on the
      electrode surface during oxidation cycles. However, by limiting the potential
      region only to the reduction side and using benzoyl peroxide (BPO) as a
      coreactant, strong ECL of TAM4 can be obtained.

PMID- 20681733
TI  - A peptidomics strategy for discovering endogenous bioactive peptides.
AB  - Peptide hormones and neuropeptides constitute an important class of naturally
      occurring peptides that are generated from precursor proteins by limited
      proteolytic processing. An important but unaddressed issue in peptidomics is to
      pin down novel bioactive peptides in a bulk of peptide sequences provided by
      tandem mass spectrometry. Here, we describe an approach to simultaneously screen
      for bioactive peptides and their target tissues. The principle behind this
      approach is to identify intact secretory peptides that have the ability to raise
      intracellular calcium levels. In practice, we used nanoflow liquid chromatography
      tandem mass spectrometry to analyze peptides released by exocytosis from cultured
      cells. Peptide sequence information was utilized to deduce intact peptide forms,
      among which those highly conserved between species are selected and tested on an
      ex vivo calcium assay using tissue pieces from transgenic mice that systemically
      express the calcium indicator apoaequorin. The calcium assay can be applied to
      various cell types, including those not amenable to in vitro culture. We used
      this approach to identify novel bioactive neuropeptides derived from the
      neurosecretory protein VGF, which evoke a calcium response in the pituitary and
      hypothalamus.

PMID- 20681734
TI  - Protein stabilization in aqueous solutions of polyphosphazene polyelectrolyte and
      non-ionic surfactants.
AB  - Applications of polyelectrolytes as pharmaceutical excipients or biologically
      active agents generated an increased interest in formulations, in which ionic
      macromolecules share the same milieu with protein drugs or vaccine antigens.
      Macromolecular interactions, which often take place in such systems, can
      potentially impact formulation activity and stability. The present article
      reports that poly[di(carboxylatophenoxy)phosphazene], disodium salt (PCPP), which
      has been previously shown to be a potent vaccine adjuvant, also displays a strong
      protein stabilizing effect in aqueous solutions that can be significantly
      amplified in the presence of nonionic surfactants. The phenomenon is studied in
      the context of macromolecular interactions in the system and is linked to the
      formation of PCPP-protein and PCPP-protein-surfactant complexes.

PMID- 20681735
TI  - Barrier films from renewable forestry waste.
AB  - Biobased free-standing films and coatings with low oxygen permeability were
      designed from a wood hydrolysate according to a recovery and formulation
      procedure that provides added value to wood converting industrial processes. Wood
      components released to the wastewater in the hydrothermal treatment of spruce
      wood were recovered and converted to an oligo- and polysaccharide-rich,
      noncellulosic fraction that was utilized in film formulations in a range of
      concentrations and compositions. Free-standing smooth and transparent films as
      well as coatings on thin PET were prepared and characterized with respect to
      oxygen permeability, tensile properties, structure, and water vapor transmission.
      With oxygen permeabilities as low as below 1 cm(3) MUm m(-2) day(-1) kPa(-1) and
      with adequate mechanical properties, the films and coatings show promising
      property profiles for renewable packaging applications.

PMID- 20681736
TI  - Dibutyl phthalate contributes to the thyroid receptor antagonistic activity in
      drinking water processes.
AB  - It has long been recognized that thyroid hormone (TH) is essential for normal
      brain development in both humans and animals, and there is growing evidence that
      environmental chemicals can disrupt the thyroid system. In the present work, we
      used a two-hybrid yeast assay to screen for agonistic or antagonistic thyroid
      receptor (TR) mediated effects in drinking waters. We found no TR agonistic, but
      TR antagonistic activities in all samples from the drinking water processes. The
      TR antagonistic activities in organic extracts of water samples were then
      calibrated regarding to a known TR-inhibitor, NH3, and were expressed as the NH3
      equivalents (TEQbio). The observed TEQbio in waters ranged from 180.8+/-24.8 to
      280.2+/-48.2 microg/L NH3. To identify the specific compounds responsible for TR
      disrupting activities, the concentrations of potentially thyroid-disrupting
      chemicals including organochlorine pesticides (OCPs), phenols, and phthalates in
      organic extracts were quantitatively determined and their toxic equivalents with
      respect to NH3 (TEQcal) were estimated from their concentration-dependent
      relationships, respectively, using the same set of bioassays. Based on the TEQ
      approach, it was revealed that dibutyl phthalate (DBP) accounted for 53.7+/-8.2%
      to 105.5+/-16.7% of TEQbio. There was no effective removal of these potential
      thyroid disrupting substances throughout drinking water treatment processes.

PMID- 20681737
TI  - Occurrence of xenobiotics in gray water and removal in three biological treatment
      systems.
AB  - Eighteen selected xenobiotics related to personal care and household chemicals
      (UV-filters, fragrances, preservatives, biocides, surfactants) were measured in
      gray water from 32 houses and in effluents of three different biological
      treatment systems (aerobic, anaerobic, and combined anaerobic+aerobic). All
      selected xenobiotics were detected in gray water samples in the low microg L(-1)
      range. Generally, lower concentrations were measured after biological treatment
      and removal efficiencies were higher under aerobic conditions than under
      anaerobic conditions. However, most of the xenobiotics were still detected in
      biologically treated gray water. The most persistent compounds were the fragrance
      tonalide and the UV-filters 2-phenyl-5-benzimidazolesulfonic acid and ethylhexyl
      methoxycinnamate. Estimated estrogenic potential of the effluent ranged between
      0.07 and 0.72 ng L(-1) of 17beta-estradiol equivalents. Depending on the
      application of the effluent and its environmental risk, physical-chemical
      processes might be required to increase the removal efficiency of these compounds
      from gray water.

PMID- 20681738
TI  - Do electrospun polymer fibers stick?
AB  - Adhesion between electrospun polycaprolactone (PCL) fibers was directly measured
      in a cross-cylinder geometry using a nanoforce tensile tester. The surface
      roughness of fibers was determined by an atomic force microscope (AFM), and the
      structural factors were characterized by differential scanning calorimeter (DSC)
      and wide-angle X-ray diffraction (WAXD). "Pull-off" force was found to be in the
      order of 10(-6) N, and the adhesion energy was 190 +/- 7 mJ/m(2). Adhesion
      increases with decreasing fiber radius. The experimental data are analyzed by the
      classical Johnson-Kendall-Roberts (JKR) contact mechanics model. The study
      provides fruitful insights into future development of bio-inspired adhesives and
      devices.

PMID- 20681739
TI  - Poly(N-isopropylacrylamide) microgels at the oil-water interface: interfacial
      properties as a function of temperature.
AB  - Highly monodisperse poly(N-isopropylacrylamide), PNiPAM, microgels were prepared
      by the conventional radical polymerization of NiPAM in the presence of
      dimethylamino ethyl methacrylate (DMAEMA) monomers at various concentrations. The
      effect of DMAEMA on the polymerization of PNiPAM microgels was examined at
      constant initiator (V50) and cross-linker (MBA) concentrations. The presence of
      DMAEMA in the synthesis batch allows for the preparation of PNiPAM microgels with
      controlled size and a narrow size distribution. The oil(dodecane)/water
      interfacial properties of the model PNiPAM microgels were then investigated. The
      pendant drop technique was used to measure the interfacial tensions as a function
      of temperature. Over the whole range of temperature (20-45 degrees C), the
      interfacial tension remains low (on the order of 17 mN/m) and goes through a
      minimum (12 mN/m) at a temperature of about 34 degrees C, which well matches the
      volume phase transition temperature (VPTT) of PNiPAM microgels. Below the VPTT,
      the decrease in the interfacial tension with temperature is likely to be due to
      the adsorption of dense layers because of the decrease of the excluded volume
      interactions. Above the VPTT, we suggest that the increase in the interfacial
      tension with temperature comes from the adsorption of loosely packed PNiPAM
      microgels. We also studied the effect of temperature on the stability of
      emulsions. Dodecane in water emulsions, which form at ambient temperature, are
      destabilized as the temperature exceeds the VPTT. In light of the interfacial
      tension results, we suggest that emulsion destabilization arises from the
      adsorption of aggregates above the VPTT and not from an important desorption of
      microgels. Aggregate adsorption would bring a sufficiently high number of
      dodecane molecules into contact with water to induce coalescence without changing
      the interfacial tension very much.

PMID- 20681740
TI  - Synthesis of thermally stable acylamino-substituted bicyclic dioxetanes and their
      base-induced chemiluminescent decomposition.
AB  - Hydroxyaryl-substituted dioxetanes 2-4 fused with a pyrrolidine ring were
      selectively synthesized by singlet oxygenation of the corresponding
      dihydropyrroles 5-7. These N-acylamino-substituted bicyclic dioxetanes were quite
      stable thermally, and 2a and 2b were estimated to possess half-lives of 32 and 34
      y at 25 degrees C. When treated with TBAF (tetrabutylammonium fluoride) in DMSO,
      these dioxetanes underwent charge-transfer-induced decomposition (CTID) to emit
      yellow-orange light. The chemiluminescence efficiencies Phi(CL) for dioxetanes 2
      ranged from 10(-6) to 10(-2). On the other hand, dioxetane 4 bearing a 4
      (benzothiazol-2-yl)-3-hydroxyphenyl moiety showed chemiluminescent decomposition
      with high efficiency (Phi(CL) = 0.15) comparable to its oxy-analogue 26.
      Prominent characteristics for CTID of the present dioxetanes were that the N
      acylamino-group influenced the color of chemiluminescence as well as the rate of
      decomposition k(CTID), and furthermore an N-acyl substituent could decisively
      affect the singlet-chemiexcitation efficiency, as observed for the case of 2b.

PMID- 20681741
TI  - Coulombic free energy of polymeric nucleic acid: low- and high-salt analytical
      approximations for the cylindrical Poisson-Boltzmann model.
AB  - An accurate analytical expression for the Coulombic free energy of DNA as a
      function of salt concentration ([salt]) is essential in applications to nucleic
      acid (NA) processes. The cylindrical model of DNA and the nonlinear Poisson
      Boltzmann (NLPB) equation for ions in solution are among the simplest approaches
      capable of describing Coulombic interactions of NA and salt ions and of providing
      analytical expressions for thermodynamic quantities. Three approximations for
      Coulombic free energy G(u,infinity)(coul) of a polymeric nucleic acid are derived
      and compared with the numerical solution in a wide experimental range of 1:1
      [salt] from 0.01 to 2 M. Two are obtained from the two asymptotic solutions of
      the cylindrical NLPB equation in the high-[salt] and low-[salt] limits: these are
      sufficient to determine G(u,infinity)(coul) of double-stranded (ds) DNA with 1%
      and of single-stranded (ss) DNA with 3% accuracy at any [salt]. The third
      approximation is experimentally motivated Taylor series up to the quadratic term
      in ln[salt] in the vicinity of the reference [salt] 0.15 M. This expression with
      three numerical coefficients (Coulombic free energy and its first and second
      derivatives at 0.15 M) predicts dependence of G(u,infinity)(coul) on [salt]
      within 2% of the numerical solution from 0.01 to 1 M for ss (a = 7 A, b = 3.4 A)
      and ds (a = 10 A, b = 1.7 A) DNA. Comparison of cylindrical free energy with that
      calculated for the all-atom structural model of linear B-DNA shows that the
      cylindrical model is completely sufficient above 0.01 M of 1:1 [salt]. The choice
      of two cylindrical parameters, the distance of closest approach of ion to
      cylinder axis (radius) a and the average axial charge separation b, is discussed
      in application to all-atom numerical calculations and analysis of experiment.
      Further development of analytical expression for Coulombic free energy with
      thermodynamic approaches accounting for ionic correlations and specific effects
      is suggested.

PMID- 20681742
TI  - Evaluation of benefit-risk.
AB  - Drug authorization, prescription and utilization are all based on benefit-risk
      assessment. This is made difficult by the apparent lack of objective means to
      measure the balance and by limitations regarding each of the two items. Benefit
      is sometimes measured by surrogate indicators of a real clinical advantage. It is
      assumed to be applicable to individuals even though it is measured in
      populations, and is represented in different ways that may convey different
      messages to physicians and patients. Risks are also hard to predict on an
      individual level. They may also be overlooked or revealed later than benefit,
      thus biasing the balance for a long time. Their causal relationship with the
      treatment is often not fully established. The benefit-risk balance itself has no
      generally recognized measure. This is why benefits and risks are hard to compare;
      either one or both may occur in single patients, and a risk-benefit profile that
      is acceptable in severe diseases may not be acceptable in diseases with a
      favourable prognosis. Pharmacoeconomics offers promising methods of health
      outcomes modelling using QALYs that take into consideration quality of life as
      well as survival. Primarily conceived as a guide for establishing the value of a
      treatment, they may prove useful as a means of trading efficacy and safety.
      However, quality of life is not always - or adequately - assessed in clinical
      studies. It is also not clear which is the most appropriate model to calculate
      QALYs for clinical purposes and how it can be used as a predictive tool at the
      individual level.

PMID- 20681743
TI  - Remote primary health care practitioners' views about priorities in Indigenous
      dementia research.

PMID- 20681744
TI  - Formulation of wax oxybenzone microparticles using a factorial approach.
AB  - Oxybenzone wax microparticles (MPs) were prepared by the hydrophobic congealable
      disperse phase method. The formulation of oxybenzone-loaded MPs was optimized
      using a 24 experimental design. Factorial analysis indicated that the main MP
      characteristics were influenced by initial drug loading, emulsification speed,
      emulsifier concentration and hydrophilic-lipophilic balance. MPs were spherical
      with 50.5-88.1 MUm size range, 17.8-38.9 drug content in mg/100 mg MPs and 33.1
      87.2% oxybenzone release in 1 h. A wide range of sunscreen delivery systems
      suitable for different formulation purposes were generated which may contribute
      to the advanced formulation of sunscreen products with improved performance.

PMID- 20681745
TI  - Scale-up of a suspension-like polymerization process for the microencapsulation
      of phase change materials.
AB  - Microcapsules of polystyrene with a high level of encapsulated paraffin wax and a
      narrow size distribution were prepared by a suspension-like polymerization
      process. The scale-up of this microencapsulation process was carried out by
      designing a pilot plant that was geometrically proportional to that used on the
      laboratory scale with the aim of preparing microcapsules with a similar particle
      size and with the same phase change material (PCM) content as those obtained in
      the laboratory. In order to verify the effectiveness of the scale-up procedure, a
      number of experiments on the pilot plant were carried out using the optimal
      formulation found on the laboratory scale. Only slight differences in mean
      particle size and encapsulated paraffin content were observed between the two
      scales at higher stirring rates. The experimental values were fitted to the
      theoretical expression for the average dissipation rate as a function of the mean
      particle size. This showed that the classical nonintermittent Kolmogoroff theory
      is applicable on the laboratory scale, whereas in the pilot plant a large
      intermittence took place, thus limiting the scale-up to higher stirring rates at
      which an equal average dissipation rate in both scales led to the same mean
      particle size. The final results indicated that the assumptions made during the
      scale-up process were correct.

PMID- 20681746
TI  - Preparation and evaluation of fast-release mephenamic acid microspheres.
AB  - Mephenamic acid is characterized by low solubility, which affects its dissolution
      rate and bioavailability. The objective of this study was to develop fast-release
      microspheres of ammonium salt of the drug (AMM) by emulsion congealing.The effect
      of polymer, drug to polymer ratio, surfactant, type and volume of oil phase,
      stirring rate, microsphere size, encapsulation efficiency and stability of the
      microspheres were investigated. The results pointed out a good yield
      (69&#x2013;98%) and encapsulation efficiency (71&#x2013;100%). Optimum conditions
      include moderate molecular weight PEG, inclusion of Tween 20 and/or Span 80, high
      ratio of PEG (1 : 4, drug : PEG), use of mineral oil and high stirring rate (2000
      rpm). Dissolution efficiency ranged between 57% and 90%. Effect of ageing on drug
      content and release revealed that the microspheres prepared remained stable
      throughout 1 year of storage. The described method was simple, efficient and
      resulted in stable microspheres with enhanced drug release.

PMID- 20681747
TI  - Formulation and in vitro evaluation of ciprofloxacin containing niosomes for
      pulmonary delivery.
AB  - In order to develop a niosome-encapsulated ciprofloxacin (CPFX) HCl formulation
      for pulmonary delivery, the feasibility of encapsulation of CPFX in niosomes, its
      stability and nebulization capability was evaluated. Various combinations of
      nonionic surfactants with cholesterol were used to prepare the formulations. The
      in vitro deposition data of the niosomal formulations were examined using an
      Andersen cascade impactor. Formulations composed of Span 60 and Tween 60 in
      combination with 40 mol% of cholesterol exhibited high encapsulation efficacy and
      stability and also had fine particle fraction and nebulization efficiency of
      about 61.9% &#x00B1; 1.0 and 77.9 &#x00B1; 2.8, respectively. Minimal inhibitory
      concentration of the niosomal CPFX against some pulmonary pathogens were lower
      than free CPFX. Using the MTT assay in human lung carcinoma cell line (A549),
      niosome-entrapped CPFX showed significantly lower cytotoxicity in comparison to
      the free drug. These results indicate that niosome can be used as a carrier for
      pulmonary delivery of CPFX via nebulization.

PMID- 20681748
TI  - Effect of carnosine and its Trolox-modified derivatives on life span of
      Drosophila melanogaster.
AB  - This study investigated the effect of antioxidants, i.e., carnosine and its
      Trolox- (water-soluble analog of alpha-tocopherol) acylated derivatives (S,S)-6
      hydroxy-2,5,7,8-tetramethylchroman-2-carbonyl-beta-alanyl-L-histidine (S,S-Trolox
      carnosine, STC) and (R,S)-6-hydroxy-2,5,7,8-tetramethylchroman-2-carbonyl-beta
      alanyl-L-histidine (R,S-Trolox-carnosine, RTC) on the life span of the fruit fly
      Drosophila melanogaster. Adding carnosine to foodstuff was accompanied and
      followed by a 20% increase in the average life span of males, but it did not
      influence the average life span of females. At the same time, adding STC to
      foodstuff prolonged average longevity both in males (by 16%) and females (by
      36%), but the addition of RTC to foodstuff had no influence upon the average life
      span of insects of either gender. The compounds studied have previously been
      shown to protect neurons of the rat brain from oxidative stress in the descending
      order of efficiency: RTC > STC > carnosine. The finding obtained in the present
      study suggests another order of efficacy regarding the effect on life span in
      male insects: STC > carnosine > RTC (inefficient). No correlation between
      antioxidant protection of rat neurons and the effect on life span of the fruit
      fly makes it possible to suppose the presence of additional cellular targets to
      be acted upon by exposure of D. melanogaster to these compounds.

PMID- 20681750
TI  - Alpha oscillations correlate with the successful inhibition of unattended
      stimuli.
AB  - Because the human visual system is continually being bombarded with inputs, it is
      necessary to have effective mechanisms for filtering out irrelevant information.
      This is partly achieved by the allocation of attention, allowing the visual
      system to process relevant input while blocking out irrelevant input. What is the
      physiological substrate of attentional allocation? It has been proposed that
      alpha activity reflects functional inhibition. Here we asked if inhibition by
      alpha oscillations has behavioral consequences for suppressing the perception of
      unattended input. To this end, we investigated the influence of alpha activity on
      motion processing in two attentional conditions using magneto-encephalography.
      The visual stimuli used consisted of two random-dot kinematograms presented
      simultaneously to the left and right visual hemifields. Subjects were cued to
      covertly attend the left or right kinematogram. After 1.5 sec, a second cue
      tested whether subjects could report the direction of coherent motion in the
      attended (80%) or unattended hemifield (20%). Occipital alpha power was higher
      contralateral to the unattended side than to the attended side, thus suggesting
      inhibition of the unattended hemifield. Our key finding is that this alpha
      lateralization in the 20% invalidly cued trials did correlate with the perception
      of motion direction: Subjects with pronounced alpha lateralization were worse at
      detecting motion direction in the unattended hemifield. In contrast,
      lateralization did not correlate with visual discrimination in the attended
      visual hemifield. Our findings emphasize the suppressive nature of alpha
      oscillations and suggest that processing of inputs outside the field of attention
      is weakened by means of increased alpha activity.

PMID- 20681749
TI  - Perception of speech in noise: neural correlates.
AB  - The presence of irrelevant auditory information (other talkers, environmental
      noises) presents a major challenge to listening to speech. The fundamental
      frequency (F(0)) of the target speaker is thought to provide an important cue for
      the extraction of the speaker's voice from background noise, but little is known
      about the relationship between speech-in-noise (SIN) perceptual ability and
      neural encoding of the F(0). Motivated by recent findings that music and language
      experience enhance brainstem representation of sound, we examined the hypothesis
      that brainstem encoding of the F(0) is diminished to a greater degree by
      background noise in people with poorer perceptual abilities in noise. To this
      end, we measured speech-evoked auditory brainstem responses to /da/ in quiet and
      two multitalker babble conditions (two-talker and six-talker) in native English
      speaking young adults who ranged in their ability to perceive and recall SIN.
      Listeners who were poorer performers on a standardized SIN measure demonstrated
      greater susceptibility to the degradative effects of noise on the neural encoding
      of the F(0). Particularly diminished was their phase-locked activity to the
      fundamental frequency in the portion of the syllable known to be most vulnerable
      to perceptual disruption (i.e., the formant transition period). Our findings
      suggest that the subcortical representation of the F(0) in noise contributes to
      the perception of speech in noisy conditions.

PMID- 20681752
TI  - Rational design, fabrication, characterization and in vitro testing of
      biodegradable microparticles that generate targeted and sustained transgene
      expression in HepG2 liver cells.
AB  - Poly(lactide-co-glycolide) (PLGA) microparticles have significant potential for
      sustained delivery of plasmid DNA (pDNA). However, unmodified PLGA microparticles
      have poor transfection efficiencies. In this study, we use several approaches to
      enhance the transfection efficiencies of PLGA microparticles in a HepG2 liver
      cell line. Polyethylenimine (PEI) is used to condense the pDNA prior to loading
      into the PLGA microparticles. This provides enhanced loading efficiencies and
      greater protection to the pDNA during the entrapment process. In addition, the
      pDNA used (ApoE) incorporates a hybrid liver-specific murine albumin
      enhancer/alpha1 antitrypsin promoter (AlbE/hAAT) to enhance transgene expression
      in human liver (HepG2) cells. The percentage of surfactant used in the
      preparation of the microparticles, the polymer composition of the PLGA, the ratio
      of the PEI to pDNA (N/P), the structure of the PEI and the potential utility of a
      galactose targeting ligand were then investigated to further optimize the
      efficacy of the cationic microparticle non-viral delivery system in transfecting
      HepG2 cells. For each PLGA PEI-pDNA microparticle formulation prepared, we
      evaluated particle size, zeta-potential, loading of pDNA, cytotoxicity, and
      transgene expression in HepG2 cells and control human embryonic kidney (HEK293)
      and monkey African green kidney fibroblast-like (COS7) cells. Loading PLGA
      particles with PEI-ApoE pDNA complexes resulted in a significant reduction in
      particle size when compared to PLGA microparticles loaded with ApoE pDNA alone.
      Scanning electron microscopy images showed that all the particle formulations
      were smooth and spherical in appearance. Incorporation of the cationic PEI in the
      PLGA particles changed the zeta-potential from negative to positive. Complexing
      PEI with ApoE pDNA increased the loading efficiency of the ApoE pDNA into the
      PLGA microparticles. The cytotoxicity of PLGA particles loaded with PEI-ApoE pDNA
      complexes was similar to PLGA particles loaded with ApoE pDNA alone. The
      transfection efficiency of all particle formulations prepared with ApoE pDNA was
      significantly higher in HepG2 cells when compared to HEK293 and COS7 cell lines.
      The release of PEI-pDNA complexes from particles prepared with different PLGA
      polymer compositions including PLGA 50-50, PLGA 75-25, and PLGA 85-15 was
      sustained in all cases but the release profile was dependent on the polymer
      composition. Transmission electron microscopy images showed that PEI-pDNA
      complexes remained structurally intact after release. The optimum formulation for
      PLGA particles loaded with PEI-ApoE pDNA complexes was prepared using 2%
      polyvinyl alcohol, 50-50 PLGA compositions and N/P ratios of 5-10. Strong
      sustained transgene expression in HepG2 cells was generated by PLGA PEI-ApoE pDNA
      particles up to the full 13 days tested.

PMID- 20681753
TI  - Longest-lived humans by month of death and month of birth.

PMID- 20681754
TI  - A new pressure-controlled colon delivery capsule for chronotherapeutic treatment
      of nocturnal asthma.
AB  - The purpose of this study was to prepare a pressure-controlled colon delivery
      capsule (PCDC) containing theophylline (TPH) dispersion in a lipid matrix as a
      chronotherapeutic drug delivery system for the treatment of nocturnal asthma. The
      system was made by film coating using Eudragit S100- based formula over the
      sealed-hard gelatin capsules containing the drug-lipid dispersion. The lipid
      formula was composed mainly of Gelucire 33/01 (G33) with different ratios of
      surfactants (1-10%). The efficiency of the prepared system was evaluated in vitro
      for its ability to withstand both the gastric and intestinal medium. In addition,
      the drug plasma concentrations were monitored after single administration to
      Beagle dogs and compared to that obtained after administration of a reference
      marketed, generic, sustained-release TPH tablets, Avolen((r)) SR. It was found
      that the optimum lipid formula was GL2 containing 90% G33 and 10% Labrasol. The
      film-coated capsules showed complete resistance to both the acidic environment
      (pH 1.2) for 2 hours and phosphate buffer pH 6.8 for 3 hours at 37 degrees C. In
      vivo evaluation of the TPH-based PCDCs showed longer lag time compared TO the
      marketed formula followed by sudden increase in TPH blood levels, which
      recommends the high potential of this system as a chronotherapeutic drug delivery
      for nocturnal asthma. The prepared PCDCs exhibited a significantly higher C(max)
      and T(max) and a nonsignificantly different AUC compared with Avolen((r)) SR.
      Higher TPH blood levels from 1 to 8 hours postadministration was detected in the
      case of the prepared PCDCs.

PMID- 20681755
TI  - The genus Artemisia: a comprehensive review.
AB  - CONTEXT: Medicinal plants are nature's gift to human beings to make disease free
      healthy life, and play a vital role to preserve our health. They are believed to
      be much safer and proven elixir in the treatment of various ailments. The genus
      Artemisia (Astraceae) consists of about 500 species, occurring throughout the
      world. The present review comprises the ethnopharmacological, phytochemical and
      therapeutic potential of various species of Artemisia. OBJECTIVE: The aim of this
      this review is to bring together most of the available scientific research
      conducted on the genus Artemisia, which is currently scattered across various
      publications. Through this review the authors hope to attract the attention of
      natural product researchers throughout the world to focus on the unexplored
      potential of Artemisia species. METHODS: This review has been compiled using
      references from major databases such as Chemical Abstracts, Medicinal and
      Aromatic Plants Abstracts, ScienceDirect, SciFinder, PubMed, King's American
      Dispensatory, Henriette's Herbal Homepage, Dr. Duke's Phytochemical and
      Ethnobotanical Databases. RESULTS: An exhaustive survey of literature revealed
      that the different species of Artemisia have a vast range of biological
      activities including antimalarial, cytotoxic, antihepatotoxic, antibacterial,
      antifungal and antioxidant activity. Some very important drug leads have been
      discovered from this genus, notably artemisinin, the well known antimalarial drug
      isolated from the Chinese herb Artemisia annua. Terpenoids, flavonoids,
      coumarins, caffeoylquinic acids, sterols and acetylenes constitute major classes
      of phytoconstituents of the genus. CONCLUSION: Various species of Artemisia seems
      to hold great potential for in-depth investigation for various biological
      activities, especially their effects on the central nervous and cardiovascular
      systems.

PMID- 20681756
TI  - Preloaded fenestrated stent-grafts for the treatment of juxtarenal aortic
      aneurysms.
AB  - PURPOSE: To describe a novel technique for target vessel catheterization in
      patients with juxtarenal abdominal aortic aneurysms requiring treatment with
      fenestrated stent-grafts (FSG). METHODS: The standard FSG design was modified,
      substituting a thin-wall tube for the solid central obturator that serves as both
      an attachment point for the distal end of the graft as well as a top cap
      retriever. Through this tube, two 0.020-inch wires are run from the hub of the
      delivery system through the stent-graft, out through each fenestration, and up to
      the proximal edge of the graft, where they are attached by sutures. The sutures
      are connected to a trigger wire on the control hub. The preloaded wires
      facilitate passage of a sheath to the fenestration, providing stability while
      target vessel catheterization takes place and avoiding the use of a large sheath
      in the contralateral groin. A third wire attached to the inside of the top cap
      facilitates its safe retrieval via a 6-mm balloon. The preloaded FSG was used in
      5 male patients (mean age 75.6 years) with either juxtarenal aneurysms (n = 2) or
      aneurysms previously treated with infrarenal stent-grafts that had developed type
      I endoleak (n = 3). In 3 cases, a double fenestrated stent-graft was required,
      and in 2 cases a triple fenestrated device was deployed, with scallops for the
      superior mesenteric or celiac arteries. RESULTS: Sixteen of 17 target vessels
      were preserved, and all aneurysms were successfully excluded with no endoleak at
      completion. In 2 patients, tortuosity encountered during device delivery caused
      twisting of the wires within the preloaded FSG, preventing successful advancement
      of a sheath over a preloaded wire. An approach from the contralateral groin was
      necessary to complete the procedure in 1 case, but the target vessel was lost in
      the other. CONCLUSION: The use of a preloaded FSG is feasible and facilitates the
      catheterization of fenestrations and of target arteries. This method has the
      potential to reduce procedure times and lower the risk of intraoperative lower
      limb ischemia.

PMID- 20681757
TI  - Commentary: the first phase of another exciting chapter in the development of
      fenestrated stent-grafts: preloaded devices.

PMID- 20681758
TI  - Challenging treatment of a secondary endoleak in a fenestrated endograft.
AB  - PURPOSE: To describe the novel use of an Amplatzer occluder device to seal a
      secondary endoleak arising at a scallop in a fenestrated stent-graft. CASE
      REPORT: A 67-year-old man with comorbidities precluding standard endovascular
      repair of a pararenal aortic aneurysm was treated with a fenestrated
      endoprosthesis containing one fenestration for the left renal artery and one
      scallop for the celiac trunk; the right renal and superior mesenteric arteries
      were occluded at presentation. Interval imaging at 2 years showed a proximal type
      I endoleak at the celiac trunk scallop associated with expansion of the aneurysm
      sac. Attempted repair with an aortic extension cuff and a "chimney" stent was
      unsuccessful. An Amplatzer Patent Foramen Ovale occluder device was deployed
      across the endoleak to provide aneurysm sac exclusion, which has been maintained
      at 6-month follow-up. CONCLUSION: Treatment of a secondary type I endoleak after
      implantation of a fenestrated endoprosthesis is challenging. The novel use of an
      Amplatzer occluder in this setting may be applicable to other situations in which
      an endovascular solution is desirable for complications of complex endovascular
      aneurysm repair.

PMID- 20681759
TI  - Commentary: new problems, new solutions: novel methods to treat a secondary type
      I endoleak in a fenestrated stent-graft.

PMID- 20681760
TI  - Initial clinical experience with the modified Zenith "Pro-Form" TX2 thoracic
      endograft.
AB  - PURPOSE: To assess the safety and efficacy of thoracic aortic endovascular repair
      (TEVAR) with the newly introduced Zenith TX2 thoracic stent-graft with Pro-Form.
      METHODS: From March 2009 to present, the Zenith TX2 with Pro-Form was used to
      treat 27 patients (23 men; median age 65 years, range 22-77) suffering from
      descending thoracic aortic disease: 20 degenerative aneurysms, 3 chronic type B
      dissections, 2 type I endoleaks following previous endograft repair, 1 aortic
      ulcer, and 1 traumatic isthmic rupture. According to Ishimaru's classification,
      the distribution of the proximal landing zone was zone 0 in 4 cases, zone 1 in 2
      cases, zone 2 in 9 cases, zone 3 in 7 cases, and zone 4 in 5 cases. One aneurysm
      distally involved the thoracoabdominal aorta. An acutely angulated (<90 degrees )
      proximal landing zone was found in 9 patients. RESULTS: The device was safely and
      effectively deployed in all cases, with no problems during sheath retrieval. The
      postoperative course was free from major complications in all cases, and there
      was no perioperative mortality. Postoperative morbidity included respiratory
      failure in 1 case, transient acute renal failure in 3 cases, and post
      implantation syndrome in 2 cases. Postoperative computed tomography at 1 and 6
      months confirmed 100% clinical success with the absence of device-related
      complications. No type I endoleak was documented. The proximal sealing stent
      fitted well with the aortic profile in all cases except one, in which
      malapposition was seen in a severely angulated aorta at 6-month follow-up.
      CONCLUSION: Based on this preliminary experience, the TX2 thoracic stent-graft
      with Pro-Form can be safely and effectively deployed to satisfactorily repair
      thoracic aortic pathology, including lesions in the arch. Stent-graft conformance
      to the aorta was excellent even in cases with unfavorable anatomy. These
      encouraging results will need to be confirmed in larger series with larger follow
      up.

PMID- 20681761
TI  - Commentary: the "pro-form" modified zenith TX2 thoracic endograft. Conformability
      + conformation = conformance: the importance of fitting the graft to the vessel.

PMID- 20681762
TI  - Morphology of aortic arch pathology: implications for endovascular repair.
AB  - PURPOSE: To present a detailed description of aortic arch morphology in patients
      with aneurysm and dissection undergoing thoracic endovascular aortic repair
      (TEVAR). METHODS: Morphological assessment of the aortic arch was performed in a
      consecutive series of patients undergoing TEVAR between November 2003 and April
      2009. In the absence of standardized reporting criteria, any patient requiring
      overstenting of the left subclavian artery (LSA) was considered to have pathology
      of the aortic arch. In all, the arch morphology of 49 patients (31 men; mean age
      70 years, range 43-86) was analyzed (25 aneurysms and 24 dissections). The
      proximal landing site of the intended stent-graft was Ishimaru zone 0 in 2 (4%)
      patients, zone 1 in 11 (22%), and zone 2 in 36 (74%). Measurements were made of
      the aortic arch diameters and angulation and the orientation and diameters of the
      supra-aortic trunks from 3-dimensional reconstructions of computed tomography
      scans. RESULTS: The diameter of the aortic arch increased as it approached the
      aortic root (mean 38.9+/-6.4 mm at the sinotubular junction versus 30.7+/-16.6 mm
      at the left subclavian artery (LSA). Mean angulation of the arch at the level of
      the LSA was 117 degrees +/-23 degrees . Five (10%) patients had a common origin
      of the innominate artery and left common carotid artery (LCCA). The distance
      between the LCCA and the LSA was <15 mm in 80%; 37 (80%) had clock-face positions
      of the LCCA and LSA ostia within 15 degrees of each other. There was no
      statistical difference in any measurements between the aneurysm and dissection
      patients. CONCLUSION: In this cohort, morphology was similar for patients with
      aneurysm or dissection. The distance between the LCCA and the LSA in the majority
      of cases was shorter than the recommendation for an adequate proximal landing
      zone. This data may assist in the development of stent-grafts for the aortic
      arch.

PMID- 20681763
TI  - Primary use of sirolimus-eluting stents in the infrapopliteal arteries.
AB  - PURPOSE: To report 12-month outcomes following application of sirolimus-eluting
      stents (SES) in infrapopliteal arteries in patients with chronic limb ischemia.
      METHODS: A prospective single-center study was conducted involving 146
      consecutive patients (102 men; mean age 73+/-9 years) with Rutherford-Becker
      categories 2 to 5 lower limb ischemia who underwent SES placement. The average
      degree of stenosis at baseline was 86%+/-5%; there were 44 (30%) occlusions. The
      main study endpoint was the 1-year primary patency rate, defined as freedom from
      in-stent restenosis (luminal narrowing > or =70%) detected with angiography or,
      if appropriate, with duplex ultrasound. Secondary endpoints included the 6-month
      primary patency rate, secondary patency rate, ankle-brachial index (ABI), and
      changes in the Rutherford-Becker classification. RESULTS: Fifteen (10%) patients
      were lost to follow-up, and 27 (18%) patients died during the follow-up period,
      leaving 104 patients undergoing the 6- and 12-month follow-up examinations. After
      6 months and 1 year, the primary patency rates were 88.5% and 83.7%,
      respectively. The mean ABI increased from 0.6+/-0.4 at baseline to 0.8+/-0.2
      after 6 months and remained significantly improved during 1-year follow-up
      (p<0.0001). The mean Rutherford-Becker classification decreased from 3.3+/-0.8 at
      baseline to 0.9+/-1.1 (p<0.0001) after 1 year. CONCLUSION: Treatment of
      infrapopliteal arteries with SES yields encouraging long-term results that
      compare favorably with previously published data on bare metal stents or plain
      balloon angioplasty.

PMID- 20681764
TI  - Commentary: infrapopliteal angioplasty with drug-eluting stents: from heart to
      toe.

PMID- 20681765
TI  - Endovascular repair of isolated iliac artery aneurysms.
AB  - PURPOSE: To retrospectively evaluate a 12-year experience with endovascular
      repair of isolated iliac artery aneurysm (IAA). METHODS: From August 1997 through
      July 2009, 91 patients (81 men; mean age 71 years, range 31-90) underwent
      endovascular treatment for isolated IAA at our department. Of these, 77 patients
      received stent-grafts either alone or in combination with coils or an Amplatzer
      vascular plug (n = 2); 1 patient received a Smart stent combined with coils, and
      13 patients were treated with coil embolization only. The aneurysms were
      classified according to location: type I = common iliac artery (CIA), type II =
      internal iliac artery (IIA), type III = CIA and IIA, and type IV = external iliac
      artery with/without CIA and/or IIA involvement. RESULTS: Primary technical
      success was 90.1% for all aneurysm types and 93.6%, 80%, 88.8%, and 93.3% for
      types I, II, III, and IV, respectively. Secondary technical success was 96.7% for
      all types and 97.8%, 95%, 100%, and 93.3%, respectively, for each type. Clinical
      success was 93.4% for all types and 97.8%, 85%, 100%, and 86.7%, respectively, by
      type. Complications in 18 (19.8%) patients included 7 type I endoleaks, 3 type II
      endoleaks, 2 enlarged aneurysm sacs (incomplete embolization), 5 cases of buttock
      claudication, and 2 stent-graft thromboses. Two patients were converted to open
      surgery; 10 underwent secondary interventions. Mortality rates were 1.1% (n = 1)
      at 30 death days and 23.1% (n = 21) over a mean follow-up of 45.9 months (no
      aneurysm-related death). Cumulative overall survival was 97.7% at 1 year and
      47.6% at 10 years. Freedom from aneurysm-related complications was 88.6% at 1
      year and 83.5% at 5 years. CONCLUSION: Endovascular repair of isolated IAA is a
      safe and minimally invasive alternative to surgery. However, it may be associated
      with several complications and must, therefore, be carefully planned.

PMID- 20681766
TI  - Endovascular treatment of common iliac artery aneurysms using the bell-bottom
      technique: long-term results.
AB  - PURPOSE: To retrospectively evaluate the long-term outcome of the bell-bottom
      technique for the endovascular repair of common iliac artery (CIA) aneurysms.
      METHODS: Between September 2003 and September 2008, 89 patients (84 men; mean age
      73.7+/-8.4 years) with aortic and CIA aneurysms were treated at 2 European
      centers with aortic extension cuffs or large iliac limbs that gave a bell-bottom
      configuration to the iliac portion of an aortoiliac stent-graft. The mean maximum
      aortic diameter was 65.7+/-12.3 mm (range 42-98), and the mean diameter of the
      treated CIA aneurysms was 22.1+/-3.0 mm (range 20-30). RESULTS: Technical success
      was achieved in 97.8% (87/89). There was no early (<30-day) mortality, but 8
      (8.9%) patients died (none aneurysm-related) during follow-up. Cumulative
      survival by Kaplan-Meier analysis was 96.3% at 1 year, 85.5% at 3 years, and
      83.1% at 5 years. After a mean follow-up of 56.5 months, computed tomography
      documented 3 (3.4%) type I endoleaks: one proximal leak was treated by conversion
      to open repair, and the other 2 distal type I endoleaks were treated by
      implantation of an iliac extension. Two (2.2%) type II endoleaks were accompanied
      by an increase in the aneurysm diameter; one was treated by coil embolization of
      the inferior mesenteric artery and the other by conversion to open repair after
      repeated coil embolization. One patient underwent thrombectomy for iliac limb
      occlusion. The freedom from secondary intervention was 91.6% at 5 years. The mean
      maximum diameter of the CIA aneurysms showed no significant change over time
      (24.1+/-3 mm at 30 days and 23.4+/-4 mm at latest follow-up). CONCLUSION:
      Moderate-size CIA aneurysms (<30 mm) can be safely and effectively treated using
      the bell-bottom technique. The risk of distal type I endoleak is low. Iliac
      related complications can be successfully treated by endovascular techniques.

PMID- 20681767
TI  - Endovascular repair of infrarenal penetrating aortic ulcers: a single-center
      experience in 20 patients.
AB  - PURPOSE: To present the early and midterm results of endovascular stent-graft
      repair in patients with infrarenal penetrating aortic ulcers (PAU). METHODS:
      Between January 1997 and December 2009, 20 patients (17 men; median age 72 years,
      range 48-85) with PAU of the infrarenal aorta underwent endovascular repair. In
      this cohort, 2 (10%) patients had a concomitant PAU in the descending thoracic
      aorta. Indications for treatment were aortic rupture in 2 patients, persistent or
      recurrent pain in 3 patients, and progression of PAU size or morphological
      aspects (e.g., thin wall) in the 15 asymptomatic patients. Follow-up included
      serial aortic imaging at predefined intervals. RESULTS: The technical success
      rate was 100%. In-hospital mortality was 10%, with 2 patients dying of myocardial
      infarction (MI). Postoperative complications were observed in 5 of 20 patients (4
      MIs, 1 case of pneumonia, 1 acute on chronic renal failure, and a lymphatic
      complication at the access site). Primary endoleaks were observed in 4 (20%)
      patients and a secondary endoleak in 1 patient. The median follow-up was 22.3
      months (range 0.4-104). The actuarial survival estimates at 1, 3, and 5 years
      were 77%, 69%, and 69%, respectively, with no aorta-related death during follow
      up. The reintervention rate during follow-up was 10%, including 1 conversion at
      11 months for type III endoleak. CONCLUSION: Patients with PAU have a significant
      number of cardiovascular comorbidities. The endovascular repair of infrarenal
      penetrating aortic ulcers thus is accompanied by mortality and morbidity caused
      predominantly by cardiac complications.

PMID- 20681768
TI  - Commentary: penetrating aortic ulcer of the abdominal aorta: an increasingly
      frequent finding.

PMID- 20681769
TI  - Aneurysm sac "thrombization" and stabilization in EVAR: a technique to reduce the
      risk of type II endoleak.
AB  - PURPOSE: To evaluate the reduction in type II endoleak risk after introducing a
      new prevention method, "thrombization" or clotting of the aneurysm sac, during
      endovascular aneurysm repair (EVAR) versus the standard EVAR technique. METHODS:
      From September 1999 to December 2008, 469 consecutive patients underwent EVAR for
      AAA at our institution. In 2003, the injection of fibrin glue with or without
      microcoils into the aneurysm sac was added to the EVAR treatment plan
      ("thrombization" technique). Patients who did not meet the inclusion criterion
      (at least 1-year follow-up imaging) were censored at the end of 2007, leaving 404
      patients eligible for the study: 224 patients (210 men; mean age 71.9+/-8.5
      years, range 25-88) undergoing EVAR alone from September 1999 to May 2003 (group
      1) compared to 180 patients (161 men; mean age 72.6+/-8 years, range 46-89) who
      underwent EVAR + thrombization from June 2003 to December 2006 (group 2).
      RESULTS: The 2 treatment groups were similar with regard to aneurysm morphology.
      No allergic or anaphylactic reactions were encountered related to the fibrin
      glue. Over median follow-up times of 72 months in group 1 and 26 months in group
      2, there were 34 (15.2%) endoleaks in group 1 versus 4 (2.2%) in group 2
      (p<0.0001). The incidence of type II endoleak was 0.25/100 person-months for
      group 1 versus 0.07/100 person-months for group 2. The preventive sac
      thrombization technique was significantly associated with a reduced risk of type
      II endoleak (HR 0.13, 95% CI 0.05 to 0.36; p<0.0001) regardless of the type of
      stent-graft fixation (infrarenal versus suprarenal). CONCLUSION: The preventive
      method of intrasac "thrombization" using fibrin glue injection with or without
      the insertion of coils proves to be a simple, low cost, safe, and effective
      technique to significantly reduce the risk of type II endoleaks irrespective of
      the endograft used.

PMID- 20681770
TI  - Commentary: reduction of type II endoleak using embolization of the aneurysm sac
      during EVAR.

PMID- 20681771
TI  - Feasibility and limitations of an automated 2D-3D rigid image registration system
      for complex endovascular aortic procedures.
AB  - PURPOSE: To examine the feasibility of an automated 2-dimensional (2D) to 3-
      dimensional (3D) image registration system to simplify the navigational
      challenges faced in complex endovascular aortic procedures. METHODS: An automated
      2D-3D image registration system was used to overlay pre-acquired 3D computed
      tomography images onto fluoroscopy images taken during endovascular aneurysm
      repair. Errors between the 3D overlay and digital subtraction angiograms were
      measured and correlated with aortic neck angulation. A mean discrepancy < or =3
      mm was considered clinically acceptable. RESULTS: There was a strong correlation
      between maximum neck angulation and maximum registration error (Pearson's r =
      0.75). Aortas with a maximum neck angulation < or =30 degrees had a mean error of
      2.5+/-1.2 mm, whereas aortas with neck angulation >30 degrees had a mean error of
      6.2+/-2.5 mm (p<0.0001). CONCLUSION: The major source of registration errors is
      aortic deformation caused by the presence of the introducer and endovascular
      graft. Further work is required if this technology is to be routinely applied to
      severely angulated aortic anatomy.

PMID- 20681772
TI  - Impact of intrasac thrombus and a patent inferior mesenteric artery on EVAR
      outcome.
AB  - PURPOSE: To assess the significance of a patent inferior mesenteric artery (IMA)
      and presence of intrasac thrombus on the outcome of endovascular aneurysm repair
      (EVAR) for infrarenal abdominal aortic aneurysm (AAA). METHODS: Between June 2004
      and June 2007, 114 AAA patients (100 men; mean age 75 years, range 56-87) treated
      electively with a bifurcated stent-graft were assessed with computed tomography
      pre- and postoperatively. Incidences of type II endoleaks and reinterventions
      were compared with preoperative intrasac thrombus and IMA patency. RESULTS: Over
      a mean follow-up of 19 months (range 6-38), there was no aneurysm rupture. Eleven
      (11%) of 101 patients with and 7 (54%) of 13 patients without preoperative
      intrasac thrombus presented with a type II endoleak (p<0.01). The postoperative
      change in aneurysm diameter was 0 mm (-20 to 16) in 18 patients with type II
      endoleak and -9 mm (-30 to 18) in sealed aneurysms (p<0.001). Fourteen (78%) type
      II endoleaks originated from lumbar arteries and 4 (22%) from the IMA in spite of
      the fact that most patients (69%) had a patent IMA. There were 5 reinterventions
      for type II endoleak with expansion of the sac. The reinterventions did not seem
      related to intrasac thrombus or a patent IMA. Prophylactic embolization of the
      IMA was unsuccessful in 4 (33%) cases. CONCLUSION: In this series, type II
      endoleaks inhibited sac shrinkage and occurred more frequently in aneurysms
      without intrasac thrombus. Most type II endoleaks originated from lumbar arteries
      and not from the IMA. Prophylactic embolization of the IMA does not seem
      justified and is not always technically successful.

PMID- 20681773
TI  - Chronic mesenteric ischemia: endovascular versus open revascularization.
AB  - To review 20 years of literature on chronic mesenteric ischemia (CMI), examining
      its complex clinical presentation and comparing open and endovascular treatment
      options. METHODS: The PubMed and EBSCOHost electronic databases were queried to
      identify English-language articles published over the last 20 years. Scrutiny of
      the retrieved articles identified 1939 patients (mean age 65 years). Of these,
      1163 patients underwent open surgery: 714 between 2000 and 2009 and 449 between
      1990 and 1999. Of the 776 patients undergoing endovascular repairs, the majority
      (684) were performed between 2000 and 2009; 92 patients were treated between 1990
      and 1999. Data were entered in an electronic database and were pooled for
      categorical analysis. RESULTS: No major differences were seen among open
      surgeries or among endovascular surgeries performed when comparing the 2 time
      periods. On comparing open and endovascular surgeries performed between 2000 and
      2009, symptom improvement was 2.4 times more likely after open compared to
      endovascular surgery (95% CI 1.5 to 3.6, p<0.001). Five-year primary patency and
      5-year assisted primary patency were 3.8 (95% CI 2.4 to 5.8, p<0.001) and 6.4
      (95% CI 1.3 to 30.1, p = 0.02) times greater in the open group. Freedom from
      symptoms at 5 years was 4.4 times greater for open versus endovascular (95% CI
      2.8 to 7.0, p<0.001). The complication rate for open versus endovascular surgery
      was 3.2 times greater (95% CI 2.5 to 4.2, p<0.001). The difference in mortality
      was not statistically significant (p = 0.75). CONCLUSION: Our data demonstrate
      that open revascularization surpasses endovascular procedures in long-term vessel
      patency and control of symptoms. Patients undergoing open procedures do, however,
      develop increased complications perioperatively. The preferred revascularization
      approach used in treating this condition should be tailored to the anatomy and
      physiology of each patient.

PMID- 20681774
TI  - Commentary: how do we decide when to stent and when to cut for mesenteric
      ischemia?

PMID- 20681775
TI  - Commentary: endovascular versus open revascularization for chronic mesenteric
      ischemia: power in numbers from experienced centers.

PMID- 20681776
TI  - Predictors of cerebral reperfusion injury after carotid stenting: the role of
      transcranial color-coded Doppler ultrasonography.
AB  - PURPOSE: To evaluate the possible role of transcranial color-coded Doppler
      ultrasonography (TCD) in predicting cerebral reperfusion injury (CRI) in patients
      undergoing carotid artery stenting (CAS) for internal carotid artery (ICA)
      stenosis. METHODS: TCD was obtained in 210 patients (149 men; mean age 64.2+/-8.4
      years, range 44-83) who underwent CAS for ICA stenosis averaging 86.7%+/-8.4%.
      Contralateral ICA occlusion or near occlusion (stenosis >90%) was present in 67
      (31.9%) patients. TCD was performed before and 24 hours after CAS with assessment
      of peak systolic velocities (PSVs) in the ipsilateral middle cerebral artery
      (iMCA) and contralateral middle cerebral artery (cMCA). PSV ratios (PSVR) in the
      iMCA and cMCA were calculated from the PSVs before and after CAS. RESULTS: CRI
      syndrome occurred in 3 (1.4%) patients (2 intracranial bleedings, 1 subarachnoid
      hemorrhage). The mean iMCA and cMCA PSVRs were 2.66+/-0.19 and 4.16+/-2.77,
      respectively, in CRI patients, while the PSVRs in CAS patients without
      neurological sequelae were 1.56+/-0.46 and 1.21+/-0.39, respectively (both
      p<0.001). The combination of iPSVR>2.4 and cPSVR>2.4 occurred in 4 patients with
      bilateral ICA disease; 3 (75%) of them developed CRI (100% sensitivity and 99%
      specificity for CRI prediction). The following independent CRI predictors were
      identified: combined iPSVR>2.4 and cPSVR>2.4 (RR 2.06, CI 1.89 to 2.24; p<0.001),
      high cMCA PSV after CAS (RR 1.23, CI 1.13 to 1.34; p<0.001), and contralateral
      ICA occlusion (RR 1.13, CI 1.03 to 1.23; p = 0.007). CONCLUSION: TCD is an
      important tool in CRI risk evaluation. The combination of iPSVR>2.4 and cPSVR>2.4
      is an independent CRI risk factor, along with contralateral ICA occlusion and
      high cMCA PSVs after CAS.

PMID- 20681777
TI  - Endovascular treatment of a traumatic direct carotid-cavernous fistula using the
      Amplatzer Vascular Plug II.
AB  - PURPOSE: To report the use of the second-generation Amplatzer Vascular Plug II
      (AVP II) for the treatment of a posttraumatic type A carotid-cavernous fistula
      (CCF). TECHNIQUE: To achieve complete treatment of a CCF, the decision was taken
      to occlude the parent carotid artery after angiographic assessment. A 6-mm AVP II
      was deployed in the petrous segment of the ICA. Post-deployment angiography
      revealed minimal residual flow, so a first-generation AVP I was also deployed.
      Immediate flow cessation was achieved, without residual proximal or distal inflow
      from the contralateral side to the fistula. At 8 months, the size of the right
      cavernous sinus had significantly reduced, with complete occlusion of the ICA and
      no residual flow in the fistula. CONCLUSION: The AVP II may be a useful
      complementary device in the neurointerventional armamentarium for parent artery
      occlusion.

PMID- 20681778
TI  - Endovascular treatment of common carotid artery dissection via the superficial
      temporal artery.
AB  - PURPOSE: To describe the endovascular treatment of an iatrogenic common carotid
      artery (CCA) dissection using the superficial temporal artery (STA) as the
      principal access. TECHNIQUE: An 83-year-old man with a post-carotid
      endarterectomy left CCA dissection was admitted for a transient ischemic attack
      involving the left cerebral hemisphere that occurred despite proper
      anticoagulation. After excluding redo surgery and transfemoral stenting (owing to
      a partially compromised aortobifemoral bypass graft), stenting of the left CCA
      dissection was planned using a right transbrachial approach, with the left STA as
      an additional access. However, intraoperative angiography showed an acute angle
      between the innominate artery and left CCA, so the STA was used as the primary
      access route owing to its straight course and 4-mm diameter. The 9-x40-mm self
      expanding stent was inserted via a 5-F sheath in the STA and deployed directly at
      the CCA dissection. The procedure was successful, and all vessels involved were
      patent at 6-month follow-up. CONCLUSION: In selected cases, the superficial
      temporal artery may represent a valid alternative approach for the endovascular
      treatment of short CCA dissections.

PMID- 20681779
TI  - Gene expression profile of human lymphocytes exposed to (211)At alpha particles.
AB  - In this study, the Whole Human Genome 44K DNA microarray assay was used for the
      first time to obtain gene expression profiles in human peripheral blood
      lymphocytes 2 h after exposure (in suspension) to 6.78 MeV mean energy alpha
      particles from extracellular (211)At. Lymphocytes were exposed to fluences of 0.3
      9.6 x 10(6) alpha particles/cm(2) [corresponding to mean absorbed alpha-particle
      doses (D(alpha)) of 0.05-1.60 Gy] over 30 min. Significantly modulated expression
      was identified in 338 early-response genes. Up-regulated expression was evident
      in 183 early-response genes, while the remaining 155 were down-regulated. Over
      half of the up-regulated genes and 40% of the down-regulated genes had a known
      biological process related primarily to cell growth and maintenance and cell
      communication. Genes associated with cell death were found only in the up
      regulated genes and those with development only in the down-regulated genes.
      Eight selected early-response genes that displayed a sustained up- or down
      regulation (CD36, HSPA2, MS4A6A, NFIL3, IL1F9, IRX5, RASL11B and SULT1B1) were
      further validated in alpha-particle-irradiated lymphocytes of two human
      individuals using the TaqMan(R) RT-qPCR technique. The results confirmed the
      observed microarray gene expression patterns. The expression modulation profiles
      of IL1F9, IRX5, RASL11B and SULT1B1 genes demonstrated similar trends in the two
      individuals studied. However, no significant linear correlation between
      increasing relative gene expression and the alpha-particle dose was evident. The
      results suggest the possibility that a panel of genes that react to alpha
      particle radiation does exist and that they merit further study in a greater
      number of individuals to determine their possible value regarding alpha-particle
      biodosimetry.

PMID- 20681780
TI  - (41)Ca in tooth enamel. Part I: a biological signature of neutron exposure in
      atomic bomb survivors.
AB  - The detection of (41)Ca atoms in tooth enamel using accelerator mass spectrometry
      is suggested as a method capable of reconstructing thermal neutron exposures from
      atomic bomb survivors in Hiroshima and Nagasaki. In general, (41)Ca atoms are
      produced via thermal neutron capture by stable (40)Ca. Thus any (41)Ca atoms
      present in the tooth enamel of the survivors would be due to neutron exposure
      from both natural sources and radiation from the bomb. Tooth samples from five
      survivors in a control group with negligible neutron exposure were used to
      investigate the natural (41)Ca content in tooth enamel, and 16 tooth samples from
      13 survivors were used to estimate bomb-related neutron exposure. The results
      showed that the mean (41)Ca/Ca isotope ratio was (0.17 +/- 0.05) x 10(-14) in the
      control samples and increased to 2 x 10(-14) for survivors who were proximally
      exposed to the bomb. The (41)Ca/Ca ratios showed an inverse correlation with
      distance from the hypocenter at the time of the bombing, similar to values that
      have been derived from theoretical free-in-air thermal-neutron transport
      calculations. Given that gamma-ray doses were determined earlier for the same
      tooth samples by means of electron spin resonance (ESR, or electron paramagnetic
      resonance, EPR), these results can serve to validate neutron exposures that were
      calculated individually for the survivors but that had to incorporate a number of
      assumptions (e.g. shielding conditions for the survivors).

PMID- 20681781
TI  - (41)Ca in Tooth Enamel. Part II: A means for retrospective biological neutron
      dosimetry in atomic bomb survivors.
AB  - (41)Ca is produced mainly by absorption of low-energy neutrons on stable (40)Ca.
      We used accelerator mass spectrometry (AMS) to measure (41)Ca in enamel of 16
      teeth from 13 atomic bomb survivors who were exposed to the bomb within 1.2 km
      from the hypocenter in Hiroshima. In our accompanying paper (Wallner et al.,
      Radiat. Res. 174, 000-000, 2010), we reported that the background-corrected
      (41)Ca/Ca ratio decreased from 19.5 x 10(-15) to 2.8 x 10(-15) with increasing
      distance from the hypocenter. Here we show that the measured ratios are in good
      correlation with gamma-ray doses assessed by electron paramagnetic resonance
      (EPR) in the same enamel samples, and agree well with calculated ratios based on
      either the current Dosimetry System 2002 (DS02) or more customized dose estimates
      where the regression slope as obtained from an errors-in-variables linear model
      was about 0.85. The calculated DS02 neutron dose to the survivors was about 10 to
      80 mGy. The low-energy neutrons responsible for (41)Ca activation contributed
      variably to the total neutron dose depending on the shielding conditions. Namely,
      the contribution was smaller (10%) when shielding conditions were lighter (e.g.,
      outside far away from a single house) and was larger (26%) when they were heavier
      (e.g., in or close to several houses) because of local moderation of neutrons by
      shielding materials. We conclude that AMS is useful for verifying calculated
      neutron doses under mixed exposure conditions with gamma rays.

PMID- 20681782
TI  - Cardiovascular diseases in the cohort of workers first employed at Mayak PA in
      1948-1958.
AB  - Incidence of and mortality from cardiovascular diseases have been studied in a
      cohort of 12,210 workers first employed at one of the main plants of the Mayak
      nuclear facility during 1948-1958 and followed up to 31 December 2000.
      Information on external gamma-ray doses is available for virtually all of these
      workers (99.9%); the mean total gamma-ray dose (+/-SD) was 0.91 +/- 0.95 Gy (99%
      percentile 3.9 Gy) for men and 0.65 +/- 0.75 Gy (99% percentile 2.99 Gy) for
      women. In contrast, plutonium body burden was measured for only 30.0% of workers;
      among those monitored, the mean cumulative liver dose from plutonium alpha
      exposure (+/- SD) was 0.40 +/- 1.15 Gy (99% percentile 5.88 Gy) for men and 0.81
      +/- 4.60 Gy (99% percentile 15.95 Gy) for women. A total of 3751 cases of
      ischemic heart disease (IHD), including 683 cases of acute myocardial infarction
      (AMI), and 1495 IHD deaths, including 338 AMI deaths, were identified in the
      study cohort during the follow-up period. Having adjusted for non-radiation
      factors, there were statistically significant increasing trends with both total
      external gamma-ray dose and internal liver dose in IHD incidence. The trend with
      internal dose was weaker and was not statistically significant after adjusting
      for external dose, whereas the external dose trend was little changed after
      adjusting for internal dose. The trend with external dose in IHD mortality was
      not statistically significantly greater than zero but was consistent with the
      corresponding trend in IHD incidence. The estimated trend in IHD mortality with
      internal dose was lower and was not statistically significant once adjustment was
      made for external dose. There was a statistically significantly increasing trend
      in AMI incidence but not AMI incidence with external dose. The risk estimates for
      IHD in relation to external radiation are generally compatible with those from
      other large occupational studies and the Japanese A-bomb survivors.

PMID- 20681783
TI  - Mobile phone radiation does not induce pro-apoptosis effects in human
      spermatozoa.
AB  - Abstract Recent reports suggest that mobile phone radiation may diminish male
      fertility. However, the effects of this radiation on human spermatozoa are
      largely unknown. The present study examined effects of the radiation on induction
      of apoptosis-related properties in human spermatozoa. Ejaculated, density
      purified, highly motile human spermatozoa were exposed to mobile phone radiation
      at specific absorption rates (SARs) of 2.0 and 5.7 W/kg. At various times after
      exposure, flow cytometry was used to examine caspase 3 activity, externalization
      of phosphatidylserine (PS), induction of DNA strand breaks, and generation of
      reactive oxygen species. Mobile phone radiation had no statistically significant
      effect on any of the parameters studied. This suggests that the impairment of
      fertility reported in some studies was not caused by the induction of apoptosis
      in spermatozoa.

PMID- 20681784
TI  - Relationship between radiosensitivity and Nrf2 target gene expression in human
      hematopoietic stem cells.
AB  - NFE2-related factor 2 (Nrf2), which belongs to the cap "n" collar family of basic
      region leucine zipper transcription factors, is a key protein in the coordinated
      transcriptional induction of expression of various antioxidant genes. The purpose
      of this study was to analyze the expression of Nrf2 target genes, such as heme
      oxygenase 1 (HO-1), ferritin heavy polypeptide 1 (FTH1), NAD(P)H dehydrogenase,
      quinone 1 (NQO1), glutamate-cysteine ligase catalytic subunit, glutamate-cysteine
      ligase modifier subunit, glutathione reductase (GSR) and thioredoxin reductase 1
      (TXNRD1), after X irradiation of CD34(+) cells that were prepared from human
      placental/umbilical cord blood hematopoietic stem cells (HSCs). We evaluated the
      relationship between radiosensitivity and expression of Nrf2 target genes in
      HSCs. The number of colony-forming cells derived from 2-Gy-irradiated HSCs
      decreased to approximately 20% of the nonirradiated control. At the same time,
      the mRNA expression of HO-1, FTH1, NQO1, GSR and TXNRD1 was significantly
      increased after X irradiation. A statistically significant negative correlation
      was observed between the surviving fraction of HSCs and the intrinsic NQO1 mRNA
      expression, indicating that HSCs in which NQO1 mRNA levels are low may also be
      radioresistant. The present results suggest that the antioxidant system
      associated with Nrf2 is involved in the radiosensitivity of HSCs.

PMID- 20681785
TI  - Quantification of gamma-H2AX foci in human lymphocytes: a method for biological
      dosimetry after ionizing radiation exposure.
AB  - Recent studies have suggested that visualization of gamma-H2AX nuclear foci can
      be used to estimate exposure to very low doses of ionizing radiation. Although
      this approach is widely used for various purposes, its suitability for individual
      human biodosimetry has not yet been assessed. We therefore conducted such an
      assessment with the help of available software for observing and automatically
      scoring gamma-H2AX foci. The presence of gamma-H2AX foci was evaluated in human
      peripheral blood lymphocytes exposed ex vivo to gamma rays in a dose range of
      0.02 to 2 Gy. We analyzed the response of gamma-H2AX to ionizing radiation in
      relation to dose, time after exposure, and individual variability. We constructed
      dose-effect calibration curves at 0.5, 8 and 16 h after exposure and evaluated
      the threshold of detection of the technique. The results show the promise of
      automatic gamma-H2AX scoring for a reliable assessment of radiation doses in a
      dose range of 0.6 Gy to 2 Gy up to 16 h after exposure. This gamma-H2AX-based
      assay may be useful for biodosimetry, especially for triage to distinguish
      promptly among individuals the ones who have received negligible doses from those
      with significantly exposures who are in need of immediate medical attention.
      However, additional in vivo experiments are needed for validation.

PMID- 20681786
TI  - Participation of DNA-PKcs in DSB repair after exposure to high- and low-LET
      radiation.
AB  - Cellular lesions (e.g. DSBs) are induced into DNA upon exposure to radiation,
      with DSB complexity increasing with radiation ionization density. Using M059K and
      M059J human glioblastoma cells (proficient and deficient in DNA-PKcs activity,
      respectively), we investigated the repair of DNA damage, including DSBs, induced
      by high- and low-LET radiation [gamma rays, alpha particles and high-charge and
      energy (HZE) ions]. In the absence of DNA-PKcs activity, less DSB repair and
      increased recruitment of RAD51 was seen at 24 h. After exposure to (56)Fe heavy
      ions, the number of cells with RAD51 tracks was less than the number of cells
      with gamma-H2AX at 24 h with both cell lines. Using alpha particles, comparable
      numbers of cells with visible gamma-H2AX and RAD51 were seen at 24 h in both cell
      lines. M059J cells irradiated with alpha particles accumulated in S phase, with a
      greater number of cyclin A and RAD51 co-stained cells seen at 24 h compared with
      M059K cells, where an S-phase block is absent. It is proposed that DNA-PKcs plays
      a role in the repair of some frank DSBs, which are longer-lived in NHEJ-deficient
      cells, and some non-DSB clustered damage sites that are converted into DSBs at
      replication as the cell cycles through to S phase.

PMID- 20681787
TI  - DNA copy number aberrations and disruption of the p16Ink4a/Rb pathway in
      radiation-induced and spontaneous rat mammary carcinomas.
AB  - Chromosomal amplifications and deletions are thought to be important events in
      spontaneous and radiation-induced carcinogenesis. To clarify how ionizing
      radiation induces mammary carcinogenesis, we characterized genomic copy number
      aberrations for gamma-ray-induced rat mammary carcinomas using microarray-based
      comparative genomic hybridization. We examined 14 carcinomas induced by gamma
      radiation (2 Gy) and found 26 aberrations, including trisomies of chromosomes 4
      and 10 for three and one carcinomas, respectively, an amplification of the
      chromosomal region 1q12 in two carcinomas, and deletions of the chromosomal
      regions 3q35q36, 5q32 and 7q11 in two, two and four carcinomas, respectively.
      These aberrations were not observed in seven spontaneous mammary carcinomas. The
      expression of p16Ink4a and p19Arf, which are located in the chromosomal region
      5q32, was always up-regulated except for a carcinoma with a homozygous deletion
      of region 5q32. The up-regulation was not accounted for by gene mutations or
      promoter hypomethylation. However, the amounts of Rb and its mRNA were down
      regulated in these carcinomas, indicating a disruption of the p16Ink4a/Rb
      pathway. This is the first report of array CGH analysis for radiation-induced
      mammary tumors, which reveals that they show distinct DNA copy number aberration
      patterns that are different from those of spontaneous tumors and those reported
      previously for chemically induced tumors.

PMID- 20681789
TI  - The induction of bystander mutagenic effects in vivo by alpha-particle
      irradiation in whole Arabidopsis thaliana plants.
AB  - Our previous studies demonstrated distant/abscopal bystander effects in A.
      thaliana seeds and embryos; the postembryonic development of bystander tissues,
      such as root hair differentiation, primary root elongation, lateral root
      initiation and survival, were inhibited significantly by localized irradiation
      with microbeam protons and low-energy ions. In the present study, we further
      investigated radiation-induced bystander mutagenic effects in vivo in A. thaliana
      plants using homologous recombination (HR) and the expression level of the HR
      related AtRAD54 gene as mutagenic end points. We found that alpha-particle
      irradiation of distal primary roots of young seedlings resulted in a significant
      increase in the frequency of HR in the aerial plants; the increased induction of
      HR occurred in every true leaf over the course of rosette development. Moreover,
      we also found that localized alpha-particle irradiation of roots induced a short
      term up-regulated expression of the HR-related AtRAD54 gene in the nonirradiated
      aerial plants. These results suggested the existence of bystander mutagenic
      effects in vivo in plants. Treatment with the ROS scavenger DMSO dramatically
      reduced the effects of localized root irradiation on the induction of HR and
      expression of the AtRAD54 gene in bystander tissues, suggesting that ROS play a
      critical role in mediating the bystander mutagenic effects in plants.

PMID- 20681788
TI  - Investigation of adaptive responses in bystander cells in 3D cultures containing
      tritium-labeled and unlabeled normal human fibroblasts.
AB  - The study of radiation-induced bystander effects in normal human cells maintained
      in three-dimensional (3D) architecture provides more in vivo-like conditions and
      is relevant to human risk assessment. Linear energy transfer, dose and dose rate
      have been considered as critical factors in propagating radiation-induced
      effects. This investigation uses an in vitro 3D tissue culture model in which
      normal AG1522 human fibroblasts are grown in a carbon scaffold to investigate
      induction of a G(1) arrest in bystander cells that neighbor radiolabeled cells.
      Cell cultures were co-pulse-labeled with [(3)H]deoxycytidine ((3)HdC) to
      selectively irradiate a minor fraction of cells with 1-5 keV/microm beta
      particles and bromodeoxyuridine (BrdU) to identify the radiolabeled cells using
      immunofluorescence. The induction of a G(1) arrest was measured specifically in
      unlabeled cells (i.e. bystander cells) using a flow cytometry-based version of
      the cumulative labeling index assay. To investigate the relationship between
      bystander effects and adaptive responses, cells were challenged with an acute 4
      Gy gamma-radiation dose after they had been kept under the bystander conditions
      described above for several hours, and the regulation of the radiation-induced
      G(1) arrest was measured selectively in bystander cells. When the average dose
      rate in (3)HdC-labeled cells (<16% of population) was 0.04-0.37 Gy/h (average
      accumulated dose 0.14-10 Gy), no statistically significant stressful bystander
      effects or adaptive bystander effects were observed as measured by magnitude of
      the G(1) arrest, micronucleus formation, or changes in mitochondrial membrane
      potential. Higher dose rates and/or higher LET may be required to observe
      stressful bystander effects in this experimental system, whereas lower dose rates
      and challenge doses may be required to detect adaptive bystander responses.

PMID- 20681790
TI  - Yields of clustered DNA damage induced by charged-particle radiations of similar
      kinetic energy per nucleon: LET dependence in different DNA microenvironments.
AB  - To determine the linear energy transfer (LET) dependence of the biological
      effects of densely ionizing radiation in relation to changes in the ionization
      density along the track, we measured the yields and spectrum of clustered DNA
      damages induced by charged particles of different atomic number but similar
      kinetic energy per nucleon in different DNA microenvironments. Yeast DNA embedded
      in agarose in solutions of different free radical scavenging capacity was
      irradiated with 1 GeV protons, 1 GeV/nucleon oxygen ions, 980 MeV/nucleon
      titanium ions or 968 MeV/nucleon iron ions. The frequencies of double-strand
      breaks (DSBs), abasic sites and oxypurine clusters were quantified. The total DNA
      damage yields per absorbed dose induced in non-radioquenching solution decreased
      with LET, with minor variations in radioquenching conditions being detected.
      However, the total damage yields per particle fluence increased with LET in both
      conditions, indicating a higher efficiency per particle to induce clustered DNA
      damages. The yields of DSBs and non-DSB clusters as well as the damage spectra
      varied with LET and DNA milieu, suggesting the involvement of more than one
      mechanism in the formation of the different types of clustered damages.

PMID- 20681791
TI  - Radical formation in lithium formate EPR dosimeters after irradiation with
      protons and nitrogen ions.
AB  - Radical formation in polycrystalline lithium formate monohydrate after
      irradiation with gamma rays, protons and nitrogen ions at room temperature was
      studied by continuous-wave electron paramagnetic resonance (EPR) spectroscopy.
      The linear energy transfer (LET) of the various radiation beams was 0.2, 0.7-3.9
      and 110-164 keV/microm for gamma rays, protons and nitrogen ions, respectively.
      Doses between 5 and 20 Gy were given. The EPR reading (the area under the EPR
      absorption resonance) increased linearly with dose for all types of radiation. As
      the LET increased, the relative effectiveness (the EPR reading per dose relative
      to that for gamma rays) decreased, while the EPR line width increased. Track
      structure theory and modeling of detector effectiveness predicted the dosimeter
      response observed after proton and nitrogen-ion irradiation. A semi-empirical
      line broadening model including dipolar spin-spin interactions was developed that
      explained the dependence of the line width on LET. The findings indicate that the
      local radical density in lithium formate is increased after high-LET irradiation.

PMID- 20681792
TI  - Identifying the high radiosensitivity of the lungs of C57L mice in a model of
      total-body irradiation and bone marrow transplantation.
AB  - Pulmonary tissue is sensitive and often treatment-limiting in patients exposed to
      total-body irradiation (TBI) in preparation for hematopoietic stem cell
      transplantation. Many rodent strains, however, exhibit a relatively high
      resistance to radiation lung damage that often requires extra radiation doses to
      be delivered locally to the thorax to generate significant levels of pulmonary
      injury. The present study compared the effects of TBI and bone marrow
      transplantation (BMT) on two mouse strains that are known to differ in lung
      radiosensitivity after whole-thorax irradiation, namely the relatively resistant
      CBA mice and the sensitive C57L mice. Evaluation by survival, microcomputerized
      tomography (micro-CT), lung tissue weights and histopathology showed that the
      C57L mice responded with severe lethal radiation pneumonitis at 4 months after
      12.5 Gy while CBA mice showed only minimal sublethal damage at this dose. C57L
      mice receiving 10 Gy TBI also had focal fibrotic lesions in the lungs out to 8
      months. The manifestation of both pneumonitis and focal fibrosis in the lungs of
      C57L mice at relatively low radiation doses points to the merits of using this
      strain in further studies aimed at exploring and ameliorating the high
      susceptibility of the lung as encountered in clinical TBI.

PMID- 20681793
TI  - Impact of RING and BRCT domain mutations on BRCA1 protein stability, localization
      and recruitment to DNA damage.
AB  - Mutations within the tumor suppressor BRCA1 cause the majority of hereditary
      breast and ovarian cancers. The BRCA1 protein is an important regulator of DNA
      double-strand break repair, and BRCA1-deficient cells are highly sensitive to
      ionizing radiation. Furthermore, BRCA1 function may contribute to enforcement of
      the G(2) cell cycle checkpoint. E3-ubiquitin ligase activity is the only known
      enzymatic activity of BRCA1, which is mediated by the N-terminal RING finger
      domain. The C-terminal BRCT repeat domain, which mediates protein-protein
      interactions, is the only other identified structural domain. By investigating
      cancer-linked mutations within each domain, we demonstrate that truncation of the
      BRCT domain greatly impairs the stability and nuclear localization of BRCA1
      protein. A missense mutation within the RING domain does not affect these
      biochemical properties. However, both mutant forms of BRCA1 fail to colocalize in
      nuclear foci with the known BRCA1-interacting proteins BARD1 and BACH1, which are
      important for DNA repair. This failure occurs despite the continued ability of
      the RING mutant protein to interact with BACH1 and the ability of the BRCT mutant
      to interact with BARD1. Furthermore, neither mutant form of BRCA1 is recruited
      into DNA damage-associated foci marked by gamma-H2AX. Therefore, our data suggest
      that both the RING and BRCT domains of BRCA1 are required for an early step in
      the function of BRCA1 during DNA repair: recruitment to the sites of DNA damage.

PMID- 20681794
TI  - Inversions in chromosome 10 of human thyroid cells induced by accelerated heavy
      ions.
AB  - Papillary thyroid carcinoma (PTC) is a known radiation-induced tumor.
      Rearrangements in human chromosome 10 and in particular intrachromosomal
      exchanges are often associated with PTC formation. In this study we measured
      intrachromosomal exchanges in human thyroid follicular cells exposed to sparsely
      or densely ionizing radiation. Assuming that inversions in chromosome 10 are a
      biomarker of PTC risk, we estimated the relative biological effectiveness (RBE)
      of heavy ions using a molecular marker in vitro. The analysis of chromosomal
      aberrations was performed with the mBAND technique, which allows detection of
      both inter- and intrachromosomal exchanges. Our results do not show any
      significant increase in the yield of intrachanges in samples exposed to heavy
      ions compared to X rays. Within the constraints imposed by the experimental model
      we used, we conclude that heavy ions would not necessarily be more effective than
      X rays in the induction of thyroid cancer.

PMID- 20681795
TI  - Influence of nuclear geometry on the formation of genetic rearrangements in human
      cells.
AB  - Interphase chromosomes are divided into discrete domains, with limited
      overlapping and movement. We explored the role of nuclear topology in the
      formation of chromosome aberrations by irradiating normal human fibroblasts with
      high-energy heavy ions from different directions. Cells with elliptical nuclei
      were grown in an aligned manner onto micrometer grooved culturing substrates to
      have a predetermined orientation with respect to the accelerated iron ions.
      Particles were directed either perpendicular to the cell layer or along the major
      or minor axis of the nucleus. Analysis of chromosome aberrations by mFISH showed
      that, at the same radiation dose, the yield of chromosomal damage and its
      complexity are largely modified by the irradiation geometry. The results
      demonstrate that the architecture of the cell nucleus determines the formation of
      chromosomal rearrangements.

PMID- 20681796
TI  - CDDO-Me protects against space radiation-induced transformation of human colon
      epithelial cells.
AB  - Radiation-induced carcinogenesis is a major concern both for astronauts on long
      term space missions and for cancer patients being treated with therapeutic
      radiation. Exposure to radiation induces oxidative stress and chronic
      inflammation, which are critical initiators and promoters of carcinogenesis. Many
      studies have demonstrated that non-steroidal anti-inflammatory drugs and
      antioxidants can reduce the risk of radiation-induced cancer. In this study, we
      found that a synthetic triterpenoid, CDDO-Me (bardoxolone methyl), was able to
      protect human colon epithelial cells (HCECs) against radiation-induced
      transformation. HCECs that were immortalized by ectopic expression of hTERT and
      cdk4 and exhibit trisomy for chromosome 7 (a non-random chromosome change that
      occurs in 37% of premalignant colon adenomas) can be transformed experimentally
      with one combined exposure to 2 Gy of protons at 1 GeV/nucleon followed 24 h
      later by 50 cGy of (56)Fe ions at 1 GeV/nucleon. Transformed cells showed an
      increase in proliferation rate and in both anchorage-dependent and independent
      colony formation ability. A spectrum of chromosome aberrations was observed in
      transformed cells, with 40% showing loss of 17p (e.g. loss of one copy of p53).
      Pretreatment of cells with pharmacological doses of CDDO-Me, which has been shown
      to induce antioxidative as well as anti-inflammatory responses, prevented the
      heavy-ion-induced increase in proliferation rate and anchorage-dependent and
      independent colony formation efficiencies. Taken together, these results
      demonstrate that experimentally immortalized human colon epithelial cells with a
      non-random chromosome 7 trisomy are valuable premalignant cellular reagents that
      can be used to study radiation-induced colorectal carcinogenesis. The utility of
      premalignant HCECs to test novel compounds such as CDDO-Me that can be used to
      protect against radiation-induced neoplastic transformation is also demonstrated.

PMID- 20681797
TI  - Bystander cell death is modified by sites of energy deposition within cells
      irradiated with a synchrotron X-ray microbeam.
AB  - Radiation-induced bystander effects are the biological responses exhibited by
      cells adjacent to cells that have been traversed by charged particles. Using a
      synchrotron X-ray microbeam irradiation system, we irradiated five cells in two
      different ways: by targeting the nuclei with 10 microm x 10-microm 5.35 keV X-ray
      beams and by irradiating the whole cells with 50 microm x 50-microm 5.35 keV X
      ray beams. Then we measured the clonogenic survival of the bystander cells. When
      only the nuclei were irradiated, a parabolic enhancement of bystander cell death
      was observed in a dose-dependent manner in the low-dose region around 1 Gy. In
      contrast, the surviving fraction of bystander cells decreased monotonically when
      whole cells were irradiated. Addition of carboxy-PTIO, a specific scavenger of
      nitric oxide (NO), suppressed bystander cell death in both cases. These results
      indicate that NO is a mediator in the induction of the parabolic and monotonic
      types of bystander cell death. Moreover, from the spatial analysis, we found that
      the parabolic type of bystander cell death was induced primarily within 1 mm of
      irradiated cells. Our findings demonstrate that the induction of bystander cell
      death depends on the sites of energy deposition in irradiated cells.

PMID- 20681798
TI  - A U-shaped dose-response relationship between x radiation and sex-linked
      recessive lethal mutation in male germ cells of Drosophila.
AB  - We reported previously that low-dose X irradiation of DNA repair-proficient
      immature sperm of wild-type Drosophila melanogaster at a low dose rate (50
      mGy/min) resulted in a mutation frequency that was lower than that in the sham
      irradiated group. Therefore, a U-shaped dose-response relationship was suggested.
      Here we show that the dose-response curve is actually U-shaped by carrying out a
      large-scale sex-linked recessive lethal assay using Drosophila. No reduction of
      the mutation frequency was observed in a strain mutant for the nucleotide
      excision repair gene mei-9a (Drosophila homologue of human XPF). Introduction of
      a chromosome fragment containing mei-9+ into the mei-9a mutant strain restored
      the reduction of the mutation frequency in the low-dose-irradiated group. These
      results showed that DNA repair was responsible for the U-shaped dose-response
      relationship in Drosophila.

PMID- 20681799
TI  - Basic fibroblast growth factor suppresses radiation-induced apoptosis and TP53
      pathway in rat small intestine.
AB  - The effect of basic fibroblast growth factor (bFGF) was studied in radiation
      induced apoptosis in rat jejunal crypt cells. Six-week-old male Wistar rats were
      administered 4 mg/kg bFGF intraperitoneally 25 h before receiving 8 Gy whole-body
      X rays. The jejunum was removed for analysis from time 0 to 120 h after
      irradiation. Villus length in control rats declined steadily until 72 h, while in
      bFGF-treated rats the villi were longer than in the controls until 48 h. Crypt
      lengths were similar to villi. bFGF treatment increased Ki-67-positive cells in
      the jejunal crypt at 0, 24 and 48 h. The treatment with bFGF reduced the number
      of apoptotic cells per jejunal crypt to 23% and 10% of the control values at 3
      and 6 h, respectively, and increased numbers of mitotic cells significantly at 48
      and 72 h. bFGF decreased the levels of TP53, CDKN1A, Puma and Cleaved caspase 3
      at 3 h as detected by Western blot analyses. Our results suggest that bFGF
      protected against acute radiation-induced injury by suppressing the crypt
      apoptotic cells including the stem cells and promoted crypt cell proliferation.
      The inhibition of apoptosis thus might be related to suppression of the TP53
      pathway.

PMID- 20681800
TI  - An orthotopic lung tumor model for image-guided microirradiation in rats.
AB  - The purpose of this study was to develop a rat orthotopic lung tumor model with a
      solitary intrapulmonary nodule to study the effects of high-dose radiation. A549
      Luc non-small cell lung cancer (NSCLC) cells were implanted into nude rats in the
      intercostal space between ribs 5 and 6 of the right lung. Bioluminescence and
      microcomputed tomography (CT) imaging were performed after implantation to
      confirm the presence of a solitary tumor and to monitor tumor growth. A device
      using image guidance for localization was developed to facilitate high-precision
      irradiation in small animals. A pilot irradiation study was performed, and
      response was assessed by bioluminescence imaging and immunohistochemistry.
      Radiation response was confirmed through serial bioluminescence imaging, and the
      strength of the bioluminescence signal was observed to be inversely proportional
      to dose. Response was also observed by the monoclonal antibody bavituximab, which
      binds to exposed lipid phosphatidylserine (PS) on tumor vessels. The ability to
      (1) reproducibly generate solitary tumor nodules in the rat lung, (2) identify
      and monitor tumor growth by bioluminescence imaging and CT imaging, (3)
      accurately target these tumors using high doses of radiation, and (4) demonstrate
      and quantify radiation response using bioluminescence imaging provides
      significant opportunity to probe the biological mechanisms of high-dose
      irradiation in preclinical settings.

PMID- 20681801
TI  - Radiation and smoking effects on lung cancer incidence among atomic bomb
      survivors.
AB  - While radiation increases the risk of lung cancer among members of the Life Span
      Study (LSS) cohort of atomic bomb survivors, there are still important questions
      about the nature of its interaction with smoking, the predominant cause of lung
      cancer. Among 105,404 LSS subjects, 1,803 primary lung cancer incident cases were
      identified for the period 1958-1999. Individual smoking history information and
      the latest radiation dose estimates were used to investigate the joint effects of
      radiation and smoking on lung cancer rates using Poisson grouped survival
      regression methods. Relative to never-smokers, lung cancer risks increased with
      the amount and duration of smoking and decreased with time since quitting smoking
      at any level of radiation exposure. Models assuming generalized interactions of
      smoking and radiation fit markedly better than simple additive or multiplicative
      interaction models. The joint effect appeared to be super-multiplicative for
      light/moderate smokers, with a rapid increase in excess risk with smoking
      intensity up to about 10 cigarettes per day, but additive or sub-additive for
      heavy smokers smoking a pack or more per day, with little indication of any
      radiation-associated excess risk. The gender-averaged excess relative risk per Gy
      of lung cancer (at age 70 after radiation exposure at 30) was estimated as 0.59
      (95% confidence interval: 0.31-1.00) for nonsmokers with a female : male ratio of
      3.1. About one-third of the lung cancer cases in this cohort were estimated to be
      attributable to smoking while about 7% were associated with radiation. The joint
      effect of smoking and radiation on lung cancer in the LSS is dependent on smoking
      intensity and is best described by the generalized interaction model rather than
      a simple additive or multiplicative model.

PMID- 20681802
TI  - Cancer mortality among women frequently exposed to radiographic examinations for
      spinal disorders.
AB  - We studied cancer mortality in a cohort of 5,573 women with scoliosis and other
      spine disorders who were diagnosed between 1912 and 1965 and were exposed to
      frequent diagnostic X-ray procedures. Patients were identified from medical
      records in 14 orthopedic medical centers in the United States and followed for
      vital status and address through December 31, 2004, using publicly available
      regional, state and nationwide databases. Causes of death were obtained from
      death certificates or through linkage with the National Death Index (NDI).
      Statistical analyses included standardized mortality ratios (SMR =
      observed/expected) based on death rates for U.S. females and internal comparisons
      using Cox regression models with attained age as the time scale. Diagnostic
      radiation exposure was estimated from radiology files for over 137,000
      procedures; estimated average cumulative radiation doses to the breast, lung,
      thyroid and bone marrow were 10.9, 4.1, 7.4 and 1.0 cGy, respectively. After a
      median follow-up period of 47 years, 1527 women died, including 355 from cancer.
      Cancer mortality was 8% higher than expected (95% CI = 0.97-1.20). Mortality from
      breast cancer was significantly elevated (SMR = 1.68; 95% CI: 1.38-2.02), whereas
      death rates from several other cancers were below expectation, in particular lung
      (SMR = 0.77), cervical (SMR = 0.31), and liver (SMR = 0.17). The excess relative
      risk (ERR) for breast cancer mortality increased significantly with 10-year
      lagged radiation dose to the breast (ERR/Gy = 3.9; 95% CI: 1.0-9.3).

PMID- 20681803
TI  - Computational electromagnetic analysis in a human head model with EEG electrodes
      and leads exposed to RF-field sources at 915 MHz and 1748 MHz.
AB  - An electromagnetic analysis of a human head with EEG electrodes and leads exposed
      to RF-field sources was performed by means of Finite-Difference Time-Domain
      simulations on a 1-mm(3) MRI-based human head model. RF-field source models
      included a half-wave dipole, a patch antenna, and a realistic CAD-based mobile
      phone at 915 MHz and 1748 MHz. EEG electrodes/leads models included two
      configurations of EEG leads, both a standard 10-20 montage with 19 electrodes and
      a 32-electrode cap, and metallic and high resistive leads. Whole-head and peak 10
      g average SAR showed less than 20% changes with and without leads. Peak 1-g and
      10-g average SARs were below the ICNIRP and IEEE guideline limits. Conversely, a
      comprehensive volumetric assessment of changes in the RF field with and without
      metallic EEG leads showed an increase of two orders of magnitude in single-voxel
      power absorption in the epidermis and a 40-fold increase in the brain during
      exposure to the 915 MHz mobile phone. Results varied with the geometry and
      conductivity of EEG electrodes/leads. This enhancement confirms the validity of
      the question whether any observed effects in studies involving EEG recordings
      during RF-field exposure are directly related to the RF fields generated by the
      source or indirectly to the RF-field-induced currents due to the presence of
      conductive EEG leads.

PMID- 20681804
TI  - The 1-carbamoyl-2-oxo-4,5-dihydroxyimidazolidine component of ROS-induced DNA
      damage in white blood cells.
AB  - The 1-carbamoyl-2-oxo-4,5-dihydroxyimidazolidine modification of cytosine is a
      known base modification produced in vitro by oxidative stress. However, the
      presence of this modification in vivo has not been established. In this study the
      introduction of this base modification into dinucleoside monophosphates was
      accomplished using the Fenton reaction. Subsequently, the modification was
      produced in short isotopically labeled oligomers. Labeled tetramers bearing the
      lesion were used as internal standards for LC-MS/MS determinations of the base
      modification in the DNA of white blood cells from healthy donors. The background
      level of the 1-carbamoyl-2-oxo-4,5-dihydroxyimidazolidine modification of
      cytosine was found to be larger than the levels of the formamide and thymine
      glycol base modifications.

PMID- 20681805
TI  - Electron emission from amorphous solid water induced by passage of energetic
      protons and fluorine ions.
AB  - Absolute doubly differential electron emission yields were measured from thin
      films of amorphous solid water (ASW) after the transmission of 6 MeV protons and
      19 MeV (1 MeV/nucleon) fluorine ions. The ASW films were frozen on thin (1
      microm) copper foils cooled to approximately 50 K. Electrons emitted from the
      films were detected as a function of angle in both the forward and backward
      direction and as a function of the film thickness. Electron energies were
      determined by measuring the ejected electron time of flight, a technique that
      optimizes the accuracy of measuring low-energy electron yields, where the effects
      of molecular environment on electron transport are expected to be most evident.
      Relative electron emission yields were normalized to an absolute scale by
      comparison of the integrated total yields for proton-induced electron emission
      from the copper substrate to values published previously. The absolute doubly
      differential yields from ASW are presented along with integrated values,
      providing single differential and total electron emission yields. These data may
      provide benchmark tests of Monte Carlo track structure codes commonly used for
      assessing the effects of radiation quality on biological effectiveness.

PMID- 20681806
TI  - Serum serotonin levels determine the magnitude and type of bystander effects in
      medium transfer experiments.
AB  - Serotonin has been shown to be involved in the production of bystander signals by
      irradiated cells. In this study we examined the levels of serotonin in 10
      different batches of commercially available fetal calf serum and correlated the
      serotonin levels with the toxicity of medium harvested from irradiated cells
      (ICCM) using a standard medium transfer colony-forming assay. The serotonin
      levels in the serum varied widely between batches, and the levels correlated
      directly with the toxicity of the harvested ICCM. Three serum samples had levels
      of serotonin below 25 ng/ml, and these did not show medium transfer bystander
      effects. Exposure of serum samples to normal daylight reduced serotonin levels
      significantly. We suggest that serum batch variability may underlie much of the
      observed interlaboratory variation in the ability to produce bystander effects
      and further suggest that serum batches should be protected from light and
      prescreened for their ability to produce a bystander effect using a positive
      control cell line.

PMID- 20681807
TI  - Bone morphogenetic protein-7 enhances cementoblast function in vitro.
AB  - BACKGROUND: Bone morphogenetic protein (BMP)-7 is a potent bone-inducing factor
      and was shown to promote periodontal regeneration in vivo and in vitro; however,
      to our knowledge, the specific effect of BMP-7 on cementoblasts has not been
      defined. We aimed to investigate the effects of BMP-7 on cementoblasts, which are
      cells responsible for tooth root-cementum formation. We hypothesized that BMP-7
      would regulate mineralized tissue-associated genes in cementoblasts and influence
      the expression profile of genes associated with cementoblast extracellular matrix
      (ECM) and cell adhesion molecules (CAMs). METHODS: A murine immortalized
      cementoblast cell line (OCCM.30) was cultured with and without 50 ng/ml BMP-7.
      After 72 hours, total RNA was isolated, and mRNA levels for bone/cementum
      markers, including bone sialoprotein (BSP), osteocalcin (OCN), osteopontin (OPN),
      and runt-related transcription factor-2 (Runx2), were investigated by real-time
      quantitative reverse transcription-polymerase chain reaction (Q-PCR). In vitro
      mineral nodule formation was assayed on day 8 using von Kossa staining. A pathway
      specific gene-expression array was used to determine BMP-7-responsive ECM and CAM
      genes in cementoblasts. RESULTS: Mineralized tissue markers were strongly
      regulated by BMP-7, with an almost three-fold increase in BSP and OCN transcripts
      and significant increases in OPN and Runx2 mRNA expressions. BMP-7 treatment
      markedly stimulated cementoblast-mediated biomineralization in vitro compared to
      untreated cells at day 8. BMP-7 treatment altered the OCCM.30 expression profile
      for ECM and CAM functional gene groups. BMP-7 tended to increase the expression
      of collagens and matrix metalloproteinases (MMPs), mildly decreased tissue
      inhibitors of MMPs (TIMPs), and had mixed regulatory effects on integrins. Using
      Q-PCR, selected array results were confirmed, including a significant BMP-7
      induced increase in MMP-3 and a decrease in TIMP-2 mRNA expression. CONCLUSION:
      These results support the promising applications of BMP-7 in therapies aimed at
      regenerating periodontal tissues lost as a consequence of disease.

PMID- 20681808
TI  - Bone regeneration around implants in periodontally compromised patients: a
      randomized clinical trial of the effect of immediate implant with immediate
      loading.
AB  - BACKGROUND: This 2-year randomized clinical trial compared bone regeneration and
      esthetic outcome between immediate and conventional loading of dental implants
      placed immediately after extraction in patients with a history of periodontal
      disease. METHODS: Patients were randomly assigned to receive immediate implants
      with either immediate loading or conventional loading after 3 months. Both groups
      received a periodontal flap, tooth extraction, implant placement, allograft bone,
      and membrane placement. The immediate loading group received a temporary crown.
      In the conventional loading group primary closure was achieved. All patients were
      followed up at 3, 6, 12, and 24 months. Evaluation included radiographic bone
      changes, papillary esthetic outcome, and implant survival rate. RESULTS: Seventy
      two patients were recruited into the study. However, 60 patients received
      immediate implant placement after extraction: 30 with conventional loading and 30
      with immediate loading. In the immediate loading group the implant survival rate
      at 2 years was 96.7%, and the mean bone gain was 1.19 mm. The corresponding
      figures in the conventional loading group were 93.3% and 1 mm. The gain in bone
      level occurred mainly from baseline to 1 year postoperatively in both groups (P
      <0.001). The papilla index decreased from baseline to 1 year in both groups (P
      <0.001) and changed only slightly thereafter. There were no significant
      differences between the two groups in the amount of bone gain or papilla index
      change during 2 years. CONCLUSIONS: Immediate loading of a single implant placed
      in a fresh extraction site in periodontally compromised patients resulted in
      similar bone gain and soft tissue esthetic outcomes compared to delayed loading.
      Primary closure and delayed loading to ensure bone regeneration around implants
      were not critical in this study.

PMID- 20681809
TI  - Association between periodontal disease and osteoporosis in postmenopausal women
      in jordan.
AB  - BACKGROUND: Some studies suggest that females with osteoporosis are at an
      increased risk of periodontal attachment loss and tooth loss; however, results
      have varied. The aim of this study is to determine the relationship between
      periodontitis and osteoporosis among postmenopausal Jordanian women. METHODS:
      This cross-sectional study includes 400 Jordanian postmenopausal women with a
      mean age of 62.5 years (SD +/- 6.4 years). These subjects were recruited from
      patients who had received a routine dual-energy x-ray absorptiometry examination
      in the Radiology Department, King Abdullah Hospital, Jordan University of Science
      and Technology, between June 2008 and February 2009. The relationship between
      skeletal bone mineral density (BMD) and radiographic and clinical parameters of
      periodontal status, including the loss of alveolar crestal height (ACH), clinical
      attachment level, probing depth, and percentage of sites with bleeding on
      probing, was evaluated after controlling for known confounders. RESULTS:
      Bivariate analyses revealed no significant differences in the severity and extent
      of clinical attachment and ACH loss among women with normal BMD, osteopenia, and
      osteoporosis. However, in the multivariate analysis, women with osteoporosis were
      more likely to have severe ACH loss (odds ratio [OR]: 4.20; 95% confidence
      interval [CI]: 1.57 to 11.22) and periodontitis (OR: 2.45; 95% CI: 1.38 to 4.34).
      CONCLUSION: Osteoporosis was significantly associated with severe alveolar
      crestal bone loss and the prevalence of periodontitis cases in postmenopausal
      Jordanian women.

PMID- 20681810
TI  - Aggregatibacter actinomycetemcomitans-induced bone loss and antibody response in
      three rat strains.
AB  - BACKGROUND: The aim of this study is to compare the colonization, immunoglobulin
      (Ig) G response, and alveolar bone loss in Aggregatibacter actinomycetemcomitans
      (Aa)-inoculated Fawn Hooded Hypertensive (FHH), Dahl Salt-Sensitive (DSS), and
      Brown Norway (BN) rats. METHODS: Each rat strain was divided into wild-type Aa
      inoculated and non-inoculated control groups. Blood taken at 12 weeks after
      inoculation was assessed for Aa-specific IgG antibodies by an enzyme-linked
      immunosorbent assay. Colonization was assessed 12 weeks postinoculation. Bone
      loss was estimated by measuring the distance from the cemento-enamel junction
      (CEJ) to the alveolar bone crest (ABC) at 20 molar sites. Colonization and
      antibody levels were compared by using the Student t test. Diseased rats were
      defined as having two sites per quadrant with CEJ-ABC distances that were
      significantly greater than the control CEJ-ABC distances. RESULTS: The Aa
      colonization of FHH rats was significantly higher than in other strains (P
      <0.05). The Aa-specific IgG levels in the DSS Aa-inoculated group were
      significantly higher than in its control group (P <0.05). Only FHH rats showed Aa
      disease-associated bone loss (P = 0.0021). CONCLUSIONS: Aa colonized and caused
      more disease in FHH rats than in the other rat strains. The rat strains each
      responded differently to the same Aa strain.

PMID- 20681811
TI  - Hydroxyapatite as an in-office agent for tooth hypersensitivity: a clinical and
      scanning electron microscopic study.
AB  - BACKGROUND: Pain caused by hypersensitivity is very common and a variety of
      agents have been tried and tested to put an end to this ailment, but with limited
      or short-term success. The search for an agent that would predictably and
      permanently occlude the tubules and blend with them has prompted the use of
      durapatite/hydroxyapatite (HAP), which is the principal inorganic constituent of
      the tooth. METHODS: A total of 486 hypersensitive teeth in 45 patients with
      hypersensitive symptoms confirmed by visual analog scale and verbal rating scale
      were divided into four groups. Two were treated with HAP in two forms (dry sol
      gel and liquid precipitate form), and the other two groups included a positive
      control group (distilled water) and a negative control group (no treatment). The
      responses were evaluated at 0 and 1 days, and 1, 2, 4, and 8 weeks, for all
      groups. Ten freshly extracted teeth were prepared and treated as mentioned
      previously and subjected to scanning electron microscopy to assess the tubule
      occlusion. RESULTS: HAP-treated teeth showed statistically significant reduction
      in hypersensitive symptoms (P <0.001) compared to the other groups at the end of
      1 day and 1, 2, and 4 weeks, but at the end of 8 weeks all four groups showed no
      statistical differences (P <0.5). The scanning electron microscopic study showed
      completely obliterated dentinal tubules in the HAP-treated specimens, whereas the
      other groups showed predominantly open or partially occluded tubules.
      CONCLUSIONS: HAP shows definite potential as an effective and permanent
      desensitizer when used as an in-office procedure. However, further long-term
      studies and comparative clinical trials with other popular desensitizing methods
      need to be carried out to prove its superiority.

PMID- 20681812
TI  - Association between interleukin-6 -174 polymorphism and Aggregatibacter
      actinomycetemcomitans in chronic periodontitis.
AB  - BACKGROUND: We previously demonstrated an association between interleukin-6 (IL
      6) polymorphisms and the detection of periodontopathogenic bacteria in aggressive
      and chronic periodontitis on a patient basis (pooled samples). The aim of this
      study is to comprehensively analyze the relative contribution of IL-6 genetic
      factors and local (tooth and site) factors on the detection of Aggregatibacter
      actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans) and
      Porphyromonas gingivalis in patients with chronic periodontitis. METHODS: Forty
      patients diagnosed with severe chronic periodontitis had subgingival samples
      harvested from four sites (the deepest probing depths in each quadrant). All
      subjects had a blood sample taken to genotype the single nucleotide polymorphism
      at position -174 in the IL-6 gene promoter. Nested polymerase chain reaction
      analysis was performed on subgingival plaque samples for the detection of A.
      actinomycetemcomitans and P. gingivalis in each of the 160 sampled sites. The
      association between IL-6 -174 genotypes and bacterial detection was investigated
      with multilevel analysis accounting for the clustering of multiple sites analyzed
      within patients. RESULTS: Respectively 60%, 62%, and 40% of subjects had A.
      actinomycetemcomitans, P. gingivalis, and both bacteria concomitantly detected in
      >=1 site. The multilevel analysis confirmed that, among all site and subject
      factors, IL-6 -174 G homozygosity showed the strongest association with the
      presence of A. actinomycetemcomitans in all subjects and in the subgroup of
      whites only. No associations were detected for P. gingivalis. CONCLUSION: This
      study provides further confirmatory evidence that the detection of A.
      actinomycetemcomitans is associated with IL-6 genetic factors in chronic
      periodontitis cases.

PMID- 20681813
TI  - Platelet-derived growth factor-BB release profile in gingival crevicular fluid
      after use of marginal periosteal pedicle graft as an autogenous guided tissue
      membrane to treat localized intrabony defects.
AB  - BACKGROUND: The aim of this study is to evaluate levels of platelet-derived
      growth factor-BB (PDGF-BB) in gingival crevicular fluid (GCF) during the early
      stages of healing for sites treated by marginal periosteal pedicle (MPP) graft as
      an autogenous guided tissue membrane compared to that of the control open flap
      debridement (OFD). METHODS: Fifteen non-smoking patients (13 males and 2 females)
      with severe chronic periodontitis participated in this prospective, controlled,
      masked trial. Each subject contributed matched pairs of 2- or 3-walled intrabony
      interproximal defects in premolar or molar teeth. Interproximal contralateral
      defects were randomly assigned to either the MPP group 1 or control OFD group 2.
      GCF samples were collected at 1, 3, 7, 14, and 30 days after surgery. PDGF-BB in
      the GCF samples was measured using a human PDGF-BB enzyme-linked immunosorbent
      assay kit. RESULTS: In both MPP and OFD, PDGF-BB concentrations peaked in the
      samples obtained during the early postoperative days (days 2 and 3) and decreased
      sharply in the samples obtained 7, 14, and 30 days post-surgery. CONCLUSION:
      Periosteal coverage of periodontal defects is not associated with a significant
      increase in PDGF-BB levels.

PMID- 20681814
TI  - Ridge augmentation using recombinant bone morphogenetic protein-2 techniques: an
      experimental study in the canine.
AB  - BACKGROUND: The use of recombinant bone morphogenetic protein-2 (rhBMP-2) with a
      collagen carrier material has severe limitations in regards to space maintenance.
      The aim of this study was to test whether rhBMP-2 combinations with allografts or
      a mesh enhance the regeneration of missing bone and the subsequent placement of
      dental implants. METHODS: In five dogs, surgically created ridge defects were
      augmented using one of the following treatment modalities: 1) rhBMP-2/absorbable
      collagen sponge (ACS) under a titanium mesh (Mesh); 2) rhBMP-2/ACS plus canine
      freeze-dried bone allograft; 3) rhBMP-2/ACS plus canine demineralized freeze
      dried bone allograft (DFDBA); or 4) rhBMP-2/ACS wrapped around a canine
      cancellous allograft block (Block Allograft). Eight weeks later, dental implants
      were placed in the augmented areas. The dogs were sacrificed 16 weeks after bone
      augmentation and specimens obtained for histologic and histomorphometric
      analyses. RESULTS: All sites augmented with DFDBA, and one site with Block
      Allograft did not allow placement of dental implants. In all other sites, dental
      implants were placed. The area of regenerated bone ranged between 23.40 mm(2)
      (freeze-dried bone allograft) and 35.16 mm(2) (Block Allograft). The greatest
      amount of bone was regenerated in the Block Allograft group ranging from 4.54 mm
      (at 1.5 mm), to 4.95 mm (at 3 mm), to 5.14 mm (at 4.5 mm). The least amount of
      bone was regenerated by the DFDBA group with values of 2.24 mm (at 1.5 mm), 2.84
      mm (at 3 mm), and 3.34 mm (at 4.5 mm). Statistically significant differences were
      observed between DFDBA and block allograft at all three levels (P <0.001).
      CONCLUSION: The combination of rhBMP-2 and a block allograft provides the
      greatest ridge width of the four treatment options used in this canine ridge
      augmentation model.

PMID- 20681815
TI  - Relationship between decrease of erythrocyte count and progression of periodontal
      disease in a rural Japanese population.
AB  - BACKGROUND: Limited research has been reported on the relationship between
      periodontal status and erythrocyte parameters. In the present study, longitudinal
      data from health checkups are used to clarify the relationship between
      periodontal disease progression and changes in parameters of erythrocytes.
      METHODS: In this prospective study, a total of 120 subjects (35 men and 85 women;
      age range: 30 to 63 years) participated in a comprehensive health screening and
      dental checkup in 2006 and 2007. Medical examinations, including anthropometric
      and manometric measurements, blood-chemistry tests, and oral examinations, were
      performed. Subjects with periodontal disease progression (i.e., the progression
      group) were defined based on the presence of >=1 tooth demonstrating a
      longitudinal loss of periodontal attachment >=3 mm or tooth loss during the study
      period. The Wilcoxon signed-rank, chi(2), Fisher exact, and Mann-Whitney U tests
      and stepwise logistic regression analysis were used for statistical analyses.
      RESULTS: The progression group comprised 30 subjects. A significant difference
      between the progression and non-progression groups was observed in changes of
      erythrocyte counts but not those of the body mass index, systolic and diastolic
      blood pressure, creatinine, fasting blood glucose, hemoglobin, hematocrit,
      triglycerides, high- and low-density lipoprotein cholesterol, total cholesterol,
      aspartate and alanine aminotransferase, and gamma-glutamyl transpeptidase.
      Stepwise logistic regression analysis showed that the progression of periodontal
      disease was associated with a change (year 2007 minus year 2006) of erythrocyte
      counts (adjusted odds ratio = 0.970; P = 0.009) after adjusting for age at
      baseline. CONCLUSION: Within the limitations of this study, the progression of
      periodontal disease is associated with a decrease in erythrocyte counts in a
      rural Japanese population.

PMID- 20681816
TI  - Analysis of complications following augmentation with cancellous block
      allografts.
AB  - BACKGROUND: Bone grafting may be associated with soft and hard tissue
      complications. Recipient site complications encountered using cancellous block
      allografts for ridge augmentation are analyzed. METHODS: A total of 101
      consecutive patients (62 females and 39 males; mean age 44 +/- 17 years) were
      treated with implant-supported restoration of 137 severe atrophic alveolar ridges
      augmented with cancellous bone-block allografts. Alveolar ridge deficiency
      locations were classified as anterior maxilla (n = 58); posterior maxilla (n = 32
      sinuses); posterior mandible (n = 32); and anterior mandible (n = 15). A total of
      271 rough-surface implants were placed. Recipient site complications associated
      with block grafting (infection, membrane exposure, incision line opening,
      perforation of mucosa over the grafted bone, partial graft failure, total graft
      failure, and implant failure) were recorded. RESULTS: Partial and total bone
      block graft failure occurred in 10 (7%) and 11 (8%) of 137 augmented sites,
      respectively. Implant failure rate was 12 (4.4%) of 271. Soft tissue
      complications included membrane exposure (42 [30.7%] of 137); incision line
      opening (41 [30%] of 137); and perforation of the mucosa over the grafted bone
      (19 [14%] of 137). Infection of the grafted site occurred in 18 (13%) of 137 bone
      blocks. Alveolar ridge deficiency location had a statistically significant effect
      on the outcome of recipient site complications. More complications were noted in
      the mandible compared to the maxilla. Age and gender had no statistically
      significant effect. CONCLUSIONS: Failures caused by complications were rarely
      noted in association with cancellous block grafting. The incidence of
      complications in the mandible was significantly higher. Soft tissue complications
      do not necessarily result in total loss of cancellous block allograft.

PMID- 20681817
TI  - Non-surgical periodontal therapy improves serum levels of C-reactive protein and
      edematous states in female patients with idiopathic edema.
AB  - BACKGROUND: The relationship between periodontal disease and systemic disease is
      revealing new and exciting associations. Idiopathic edema presents a clinical
      syndrome with obscure pathophysiology. The present study investigates whether non
      surgical periodontal therapy is beneficial in patients who are not responding to
      conventional treatment of idiopathic edema. METHODS: Thirty patients with
      idiopathic edema were allocated to intervention and control groups. All the
      subjects were assessed for systemic (body weight, body mass index, visual scale
      of edema, serum C-reactive protein, and serum albumin) and periodontal (plaque
      index, calculus index, and gingival index) parameters. Non-surgical periodontal
      therapy, including oral hygiene instructions, scaling and root planing, and
      systemic antibiotic therapy, was provided in the intervention group. Both groups
      were reevaluated after 4 weeks. RESULTS: Both groups were comparable at baseline.
      All parameters, except serum albumin, showed significant improvement after
      periodontal therapy. The control group showed further worsening of these
      parameters. CONCLUSIONS: This study shows that sources for systemic inflammation,
      such as periodontal disease, could affect the pathogenesis of idiopathic edema.
      Successful elimination of such covert sources of inflammation leads to a clinical
      benefit in patients who are distressed by this condition.

PMID- 20681818
TI  - Randomized, controlled, single-masked, clinical study to compare and evaluate the
      efficacy of microspheres and gel in periodontal pocket therapy.
AB  - BACKGROUND: The aim of this randomized, split-mouth, single-masked study is to
      compare the efficacy of a gel and microspheres as drug-delivery systems in the
      treatment of periodontal disease. METHODS: Microspheres were prepared, the
      release patterns of the microspheres and gel formulations were analyzed using an
      ultraviolet spectrophotometer, and particle shapes were studied under a scanning
      electron microscope. A split-mouth design was followed in which 30 potential
      sites were identified and divided into three groups: one control group and two
      groups in which microspheres or a gel was placed. Patients were recalled at 1, 3,
      6, and 9 months. Clinical recordings included plaque index (PI), gingival index
      (GI), probing depth (PD), and relative attachment level (RAL) measurements;
      subgingival plaque was also obtained for microbiologic examination prior to and
      after therapy. RESULTS: Microspheres had a more sustained release and a high
      initial drug concentration. There was a significant improvement in the PI and GI
      in the initial 3 months. The results were statistically significant at P = 0.01.
      The mean PD scores among scores for the three groups at baseline and follow-up
      visits showed a reduction of 0.4 to 1 mm. The microbiologic parameters were also
      statistically significant. CONCLUSION: These data suggest that the type of
      delivery system could significantly influence the outcome of therapy.

PMID- 20681820
TI  - Errors in transfusion medicine are not only misidentifications of the recipient,
      but also pre-analytical and analytical errors.

PMID- 20681887
TI  - Genetic and household determinants of predisposition to human hookworm infection
      in a Brazilian community.
AB  - BACKGROUND: Predisposition to heavy or light human hookworm infection is
      consistently reported in treatment-reinfection studies. A significant role for
      host genetics in determining hookworm infection intensity has also been shown,
      but the relationship between host genetics and predisposition has not been
      investigated. METHODS: A treatment-reinfection study was conducted among 1302
      individuals in Brazil. Bivariate variance components analysis was used to
      estimate heritability for pretreatment and reinfection intensity and to estimate
      the contribution of genetic and household correlations between phenotypes to the
      overall phenotypic correlation (ie, predisposition). RESULTS: Heritability for
      hookworm egg count was 17% before treatment and 25% after reinfection.
      Predisposition to heavy or light hookworm infection was observed, with a
      phenotypic correlation of 0.34 between pretreatment and reinfection intensity.
      This correlation was reduced to 0.23 after including household and environmental
      covariates. Genetic and household correlations were 0.41 and 1, respectively, and
      explained 88% of the adjusted phenotypic correlation. CONCLUSIONS: Predisposition
      to human hookworm infection in this area results from a combination of host
      genetics and consistent differences in exposure, with the latter explained by
      household and environmental factors. Unmeasured individual-specific differences
      in exposure did not contribute to predisposition.

PMID- 20681888
TI  - Adherence to biologic DMARD therapies in rheumatoid arthritis.
AB  - IMPORTANCE OF THE FIELD: The efficacy of the biologic disease-modifying
      antirheumatic drugs (DMARDs) shown in clinical trials may be jeopardized due to
      prevalent poor patient adherence. AREAS COVERED IN THIS REVIEW: Patient adherence
      including compliance and persistence with biologic DMARDs in rheumatoid
      arthritis. WHAT THE READER WILL GAIN: This is a comprehensive review of the
      literature. The various definitions and methodologies of measurement used in
      adherence research are reviewed and data are presented by separating compliance
      and persistence. Differences in compliance rates were mainly based on numerical
      trends. There was evidence for and against greater persistence with infliximab
      versus adalimumab and etanercept. There was a trend in favour of greater
      compliance and lower persistence with TNF-alpha inhibitor monotherapy versus in
      combination therapy with methotrexate. TAKE HOME MESSAGE: The evidence suggests
      that adherence to biologic DMARDs is suboptimal. When further research is applied
      in the field, agreed definitions and methodology need to be used to allow for
      cross-study comparisons. In addition, adherence should be assessed in conjunction
      with clinical outcomes and not on its own so that it can be better understood
      what levels of adherence provide the required clinical outcomes.

PMID- 20681927
TI  - Prolonged jaundice in newborns is associated with low antioxidant capacity in
      breast milk.
AB  - In breastfeeding newborns who are otherwise healthy, the mechanism of prolonged
      jaundice remains unclear. The aim of this study was to investigate relations
      between prolonged jaundice and oxidative parameters in breast milk. Full-term,
      otherwise healthy newborns with jaundice lasting more than 2 weeks were enrolled
      prospectively in the study. As a control group, newborns in the same age group
      but without prolonged jaundice were selected. All newborns in the study were
      exclusively breastfed. In the newborns with prolonged jaundice, investigations of
      the etiology of the jaundice included complete blood count, peripheral blood
      smear, blood typing, direct Coombs test, measurement of serum levels of total and
      direct bilirubin, tests for liver and thyroid function (TSH, free T4, total T4),
      urine culture and measurement of urine reducing substances, and determination of
      glucose 6 phosphate dehydrogenase enzyme levels. Breast milk was collected from
      the mothers of the newborns in both groups. The antioxidant status of the breast
      milk was assessed via determination of total antioxidant capacity (TAC).
      Oxidative stress was also assessed in breast milk by measurement of total
      oxidation status (TOS) and calculation of the oxidative stress index (OSI). The
      prolonged jaundice group differed significantly from the control group in terms
      of mean TAC and OSI (p < 0.001), but not in terms of TOS. In conclusion, in the
      breast milk of mothers of newborns with prolonged jaundice, oxidative stress was
      found to be increased, and protective antioxidant capacity was found to be
      decreased.

PMID- 20681928
TI  - Design of an automated device to measure sagittal plane stiffness of an
      articulated ankle-foot orthosis.
AB  - The purpose of this study was to design a new automated stiffness measurement
      device which could perform a simultaneous measurement of both dorsi- and
      plantarflexion angles and the corresponding resistive torque around the
      rotational centre of an articulated ankle-foot orthosis (AAFO). This was achieved
      by controlling angular velocities and range of motion in the sagittal plane. The
      device consisted of a hydraulic servo fatigue testing machine, a torque meter, a
      potentiometer, a rotary plate and an upright supporter to enable an AAFO to be
      attached to the device via a surrogate shank. The accuracy of the device in
      reproducing the range of motion and angular velocity was within 4% and 1%
      respectively in the range of motion of 30 degrees  (15 degrees  plantarflexion to
      15 degrees  dorsiflexion) at the angular velocity of 10 degrees /s, while that in
      the measurement of AAFO torque was within 8% at the 0 degrees  position. The
      device should prove useful to assist an orthotist or a manufacturer to quantify
      the stiffness of an AAFO and inform its clinical use.

PMID- 20681929
TI  - Biomechanical differences between two exoprosthetic hip joint systems during
      level walking.
AB  - Previous studies have shown low end-user acceptance of a hip disarticulation
      style prosthesis and that the limitations of such prostheses, including poor gait
      pattern, socket discomfort, weight of the prosthesis, loss of mobility,
      instability and high energy consumption are a contributing factor. This study was
      initiated to determine if a new style of prosthetic hip joint could help to
      overcome some of the limitations concerning the gait pattern. The present study
      analyzed the gait pattern of six hip disarticulation amputee subjects. The
      objective was to compare two different prosthetic hip joints, both from Otto Bock
      HealthCare: The new Helix(3D) and the 7E7, which is based on the Canadian model
      proposed by McLaurin (1954). Kinematics and kinetics were recorded by an
      optoelectronic camera system with six CCD cameras and two force plates. During
      weight acceptance, the Helix(3D) extends considerably slower and reaches full
      extension later than the 7E7. The increased range of pelvic tilt observed with
      hip disarticulation amputees is significantly reduced (by 5 +/- 3 degrees) when
      using the Helix(3D) Hip Joint. In addition, this system showed increased stance
      phase knee joint flexion as well as increased maximum swing phase knee flexion
      angles compared to the 7E7. These motion analysis results show that the Helix(3D)
      Hip Joint can reduce gait abnormalities compared to the uniplanar design of the
      7E7 hip joint.

PMID- 20681930
TI  - Testosterone is not associated with mortality in older African-American males.
AB  - INTRODUCTION. Although testosterone and its association with disease progression
      and mortality is a widely studied topic, no studies have evaluated mortality
      risks related to testosterone levels in an older African-American population. The
      mechanisms for known racial differences in mortality risk for certain cancers and
      cardiovascular risk factors are largely unknown. Elucidating a mortality risk
      associated with testosterone levels may give insight into the elevated risk for
      certain diseases in African-Americans. METHODS AND RESULTS. Study data were
      derived from a cohort 622 African-Americans (age 80.05  +/-  6.4, range 68-102)
      from Saint Louis, Missouri that includes 190 males (age 79.38  +/-  6.2, range 70
      102). The eligible sample for this report includes 56 of the 190 males (age 78.89
      +/-  6.9, range 70-102) who donated blood at baseline in 1992-1994 and
      subsequently tested for total testosterone and bioavailable testosterone.
      Covariates for adjusted analyses were lower body functional limitations,
      physician visits and comorbidities, also collected at baseline. Males' mean
      bioavailable testosterone levels (ng/dl) were 33.33  +/-  24.4 (n above 70 ng/dl
      = 5) and mean total testosterone levels (ng/dl) were 246.63  +/-  118.7 (n above
      300 ng/dl = 20). Vital status was determined through 2002; 41 males (73%) were
      deceased and 15 were alive. Mortality did not differ among males with
      testosterone levels <300 versus 300+ (p = 0.42) or with bioavailable testosterone
      levels <70 versus > 70 (p  =  0.34). Total testosterone levels did not predict
      mortality when adjusted for age (Adjusted Hazard Ratio [AHR] = 0.998; 95%
      confidence interval [CI] 0.995-1.001; p = 0.28) or adjusted for age and other
      covariates (AHR  =  0.099; 95% CI 0.996, 1.002; p  =  0.35). Bioavailable
      testosterone levels did not predict mortality when adjusted for age (AHR  = 
      0.992; 95% CI .977-1.007; p  =  0.30) or when adjusted for age and other
      covariates (AHR 0.991; 95% CI .976-1.006; p  =  0.261). CONCLUSION. In older
      African-American males, total and bioavailable testosterone levels, with and
      without adjustment for covariates, are not independently associated with
      mortality risk.

PMID- 20681943
TI  - Genetic polymorphisms and atrial fibrillation: Insights into the prothrombotic
      state and thromboembolic risk.
AB  - The pathophysiology of thromboembolism in atrial fibrillation (AF) is a
      multifactorial and complex process. Abnormalities of haemostasis, fibrinolysis,
      endothelium, and platelets have all been described in AF. This prothrombotic
      state observed in AF appears to be additive to the presence of clinical and
      echocardiography risk factors for thromboembolism. Nonetheless, the precise
      mechanistic pathway(s) leading to the prothrombotic state in AF remain to be
      elucidated. Of note, there are limited data on the influence of genetic
      polymorphisms in thromboembolic risk associated with AF. On the other hand, the
      response to coumarin derivatives depends on several factors, such as sex, age,
      diet, or interacting drugs. Optimal anticoagulation control is usually hampered
      by significant interindividual variability in dose requirements for a given
      target level of anticoagulation. There is increasing evidence that
      interindividual sensitivity and side-effects to coumarinics may be largely
      determined genetically. Thus, genetic polymorphisms could explain the individual
      risk of developing an adverse drug reaction (bleeding) or drug inefficacy
      (thrombosis) with oral anticoagulation. In this article, we provide an overview
      of the limited data about the possible influence of genetic polymorphisms on
      thromboembolic risk in AF, as well as the genetic influences on anticoagulant
      drug responsiveness.

PMID- 20681944
TI  - Adenosine receptor ligands: where are we, and where are we going?

PMID- 20681945
TI  - The medicinal chemistry of targeted tumor imaging (I).

PMID- 20681946
TI  - The medicinal chemistry of targeted tumor imaging (II).

PMID- 20681947
TI  - Chemokine receptors as targets in medicinal chemistry and drug discovery.

PMID- 20681948
TI  - RING domain dimerization is essential for RNF4 function.
AB  - RNF4 [RING (really interesting new gene) finger protein 4] family ubiquitin
      ligases are RING E3 ligases that regulate the homoeostasis of SUMOylated proteins
      by promoting their ubiquitylation. In the present paper we report that the RING
      domain of RNF4 forms a stable dimer, and that dimerization is required for
      ubiquitin transfer. Our results suggest that the stability of the E2~ubiquitin
      thioester bond is regulated by RING domain dimerization.

PMID- 20681949
TI  - Lentivirus-mediated expression of insulin-like growth factor-I promotes neural
      stem/precursor cell proliferation and enhances their potential to generate
      neurons.
AB  - Strategies to enhance neural stem/precursor cell (NPC) capacity to yield
      multipotential, proliferative, and migrating pools of cells that can efficiently
      differentiate into neurons could be crucial for structural repair after
      neurodegenerative damage. Here, we have generated a lentiviral vector for
      expression of insulin-like growth factor-I (IGF-1) and investigated the impact of
      IGF-1 transduction on the properties of cultured NPCs (IGF-1-NPCs). Under
      proliferative conditions, IGF-1 transduction promoted cell cycle progression via
      cyclin D1 up-regulation and Akt phosphorylation. Remarkably upon differentiation
      inducing conditions, IGF-1-NPCs cease to proliferate and differentiate to a
      greater extent into neurons with significantly longer neurites, at the expense of
      astrocytes. Moreover, using live imaging we provide evidence that IGF-1
      transduction enhances the motility and tissue penetration of grafted NPCs in
      cultured cortical slices. These results illustrate the important consequence of
      IGF-1 transduction in regulating NPC functions and offer a potential strategy to
      enhance the prospective repair potential of NPCs.

PMID- 20681950
TI  - Pre-synaptic BK channels selectively control glutamate versus GABA release from
      cortical and hippocampal nerve terminals.
AB  - In the present study, by means of genetic, biochemical, morphological, and
      electrophysiological approaches, the role of large-conductance voltage- and
      Ca(2+)-dependent K(+) channels (BK channels) in the release of excitatory and non
      excitatory neurotransmitters at hippocampal and non-hippocampal sites has been
      investigated. The results obtained show that the pharmacological modulation of
      pre-synaptic BK channels selectively regulates [(3)H]D-aspartate release from
      cortical and hippocampal rat synaptosomes, but it fails to influence the release
      of excitatory neurotransmitters from cerebellar nerve endings or that of
      [(3)H]GABA, [(3)H]Noradrenaline, or [(3)H]Dopamine from any of the brain regions
      investigated. Confocal immunofluorescence experiments in hippocampal or
      cerebrocortical nerve terminals revealed that the main pore-forming BK alpha
      subunit was more abundantly expressed in glutamatergic (vGLUT1(+)) versus
      GABAergic (GAD(65-67)(+)) nerve terminals. Double patch recordings in
      monosynaptically connected hippocampal neurons in culture confirmed a
      preferential control exerted by BK channels on glutamate over GABA release.
      Altogether, the present results highlight a high degree of specificity in the
      regulation of the release of various neurotransmitters from distinct brain
      regions by BK channels, supporting the concept that BK channel modulators can be
      used to selectively limit excessive excitatory amino acid release, a major
      pathogenetic mechanism in several neuropsychiatric disorders.

PMID- 20681951
TI  - TGF-beta and LPS modulate ADP-induced migration of microglial cells through P2Y1
      and P2Y12 receptor expression.
AB  - Nucleotides act as early signals for microglial recruitment to sites of CNS
      injury. As microglial motility and activation can be influenced by several local
      factors at the site of the lesion, we investigated the effects of interferon
      gamma, lipopolysaccharide (LPS) or transforming growth factor-beta (TGF-beta)
      addition to mixed glial cell cultures, on microglial migration in response to
      ADP, P2Y12 and P2Y1 mRNA expression as well as on the expression of an array of
      genes associated with the process of microglial activation. First, we
      demonstrated, by pharmacological inhibition and by using small interfering RNAs,
      that in addition to P2Y12, P2Y1 is involved in ADP-stimulated microglial
      migration. The ability of specific agonists to induce Ca(2+) mobilization further
      confirmed the expression of functional P2Y receptors in microglia. Then, we found
      that migratory capability and expression of both P2Y receptors were abrogated in
      microglial cells from LPS-stimulated mixed glial cultures, while TGF-beta
      increased ADP-induced migration and the expression of P2Y12 and P2Y1 receptors.
      Interferon-gamma did not influence receptor expression or microglial migration.
      Finally, the patterns of gene expression induced in microglia by LPS or TGF-beta
      treatment of mixed glial cultures were clearly distinct. LPS induced a set of
      classical pro-inflammatory genes, whereas TGF-beta increased the expression of
      genes associated with atypical microglial phenotype, namely arginase-1 and TGF
      beta genes. These results imply that both P2Y1 and P2Y12 may guide microglia
      toward the lesion. They also suggest that the modulation of microglial purinergic
      receptors expression by local factors, through direct and/or astrocyte-mediated
      actions, may represent a novel mechanism affecting neuroinflammatory response.

PMID- 20681952
TI  - Glypican-1 facilitates prion conversion in lipid rafts.
AB  - The conformational conversion of the cellular prion protein (PrP(C)) to the
      infectious form (PrP(Sc)) is the critical step in the pathogenesis of prion
      diseases such as Creutzfeldt-Jakob disease in humans and scrapie in sheep.
      Cholesterol-rich lipid rafts play a key role in the conversion of PrP(C) to
      PrP(Sc) and other cellular components have been identified as important cofactors
      to trigger, enhance, or accelerate prion formation. Amongst these heparan
      sulphate proteoglycans (HSPGs) and their glycosaminoglycan side-chains have been
      implicated in prion metabolism. Recently, the cell-surface HSPG glypican-1 was
      demonstrated to co-localise with PrP(C) on the cell surface and to promote its
      association with lipid rafts. Both PrP(C) and PrP(Sc) co-immunoprecipitated with
      glypican-1 and the interaction was dependent on the glycosaminoglycan side chains
      of glypican-1. Critically, depletion of glypican-1 in scrapie-infected N2a cells
      reduced the formation of PrP(Sc), indicating that this HSPG is involved in prion
      formation. Further work is required to understand the molecular and cellular
      mechanisms underpinning the role of glypican-1 and possibly other members of the
      glypican family in prion metabolism, and to determine whether glypican-1
      facilitates PrP(Sc) formation in vivo.

PMID- 20681953
TI  - Long-acting genipin derivative protects retinal ganglion cells from oxidative
      stress models in vitro and in vivo through the Nrf2/antioxidant response element
      signaling pathway.
AB  - Previously, we reported that genipin, a herbal iridoid, had neuritogenic and
      neuroprotective actions on PC12 cells. Although nitric oxide (NO)-activated
      signalings were proposed to be neuritogenic, the neuroprotective action of
      genipin remains to be elucidated. From the standpoint of NO activation, we tested
      a possible protective mechanism through the nitrosative Kelch-like ECH-associated
      protein (Keap1)/NF-E2-related factor 2 (Nrf2)-antioxidant response element
      pathway in rat retinal ganglion cells (RGC-5 cells) in culture, and in vivo,
      against hydrogen peroxide and optic nerve injury (ONI), respectively, using a
      long-acting (1R)-isoPropyloxygenipin (IPRG001). IPRG001 induced NO generation and
      the expressions of antioxidative enzymes, such as heme oxygenase-1 (HO-1), in RGC
      5 cells. The protective action of IPRG001 depended on HO-1 and NO induction. We
      found that S-nitrosylation of Keap1 by IPRG001 may contribute to translocation of
      Nrf2 to the nucleus and triggered transcriptional activation of antioxidative
      enzymes. Furthermore, apoptotic cells were increased and 4-hydroxy-2-nonenal was
      accumulated in rat retina following ONI. Pre-treatment with IPRG001 almost
      completely suppressed apoptosis and accumulation of 4-hydroxy-2-nonenal in RGCs
      following ONI accompanied by HO-1 induction. These data demonstrate for the first
      time that IPRG001 exerts neuroprotective action in RGCs in vitro and in vivo,
      through the Nrf2/antioxidant response element pathway by S-nitrosylation against
      oxidative stress.

PMID- 20681954
TI  - gamma-Hydroxybutyrate and the GABAergic footprint: a metabolomic approach to
      unpicking the actions of GHB.
AB  - Gamma-hydroxybutyrate is found both naturally in the brain and self-administered
      as a drug of abuse. It has been reported to act at endogenous gamma
      hydroxybutyrate (GHB) receptors and GABA(B) receptors [GABA(B)R], and may also be
      metabolized to GABA. Here, the metabolic fingerprints of a range of
      concentrations of GHB were measured in brain cortical tissue slices and compared
      with those of ligands active at GHB and GABA-R using principal components
      analysis (PCA) to identify sites of GHB activity. Low concentrations of GHB (1.0
      MUM) produced fingerprints similar to those of ligands active at GHB receptors
      and alpha4-containing GABA(A)R. A total of 10 MUM GHB clustered proximate to
      mainstream GABAergic synapse ligands, such as 1.0 MUM baclofen, a GABA(B)R
      agonist. Higher concentrations of GHB (30 MUM) clustered with GABA(C)R agonists
      and the metabolic responses induced by blockade of the GABA transporter-1 (GAT1).
      The metabolic responses induced by 60 and 100 MUM GHB were mimicked by
      simultaneous blockade of GAT1 and GAT3, addition of low concentrations of
      GABA(C)R antagonists, or increasing cytoplasmic GABA concentrations by incubation
      with the GABA transaminase inhibitor vigabatrin. These data suggest that at
      concentrations > 30 MUM, GHB may be active via metabolism to GABA, which is then
      acting upon an unidentified GABAergic master switch receptor (possibly a high
      affinity extrasynaptic receptor), or GHB may itself be acting directly on an
      extrasynaptic GABA-R, capable of turning off large numbers of cells. These
      results offer an explanation for the steep dose-response curve of GHB seen in
      vivo, and suggest potential target receptors for further investigation.

PMID- 20681955
TI  - Munc18-1 as a key regulator of neurosecretion.
AB  - Munc18-1 plays essential roles in neurosecretion by interacting with syntaxin-1
      and controlling the formation of the soluble N-ethylmaleimide-sensitive factor
      attachment protein receptors (SNARE) complex. At least three important functions
      of Munc18-1 have been proposed: (i) molecular chaperone of syntaxin-1 for
      appropriate localization and expression of syntaxin-1, (ii) priming/stimulation
      of the SNARE-mediated membrane fusion, and (iii) docking of large dense-core
      vesicles to the plasma membrane. Similarly, at least two different binding modes
      have been proposed for the interaction between Munc18-1 and syntaxin-1: (i)
      binary binding to a 'closed' conformation of syntaxin-1, and (ii) binding to the
      N-terminal peptide of syntaxin-1, which is thought to enable an interaction with
      the quaternary SNARE complex and/or further stabilize the binary interaction
      between Munc18-1 and closed syntaxin-1. Recent structural analyses have
      identified critical Munc18-1 residues implicated in these different modes of
      binding. These have recently been tested functionally in rescue experiments using
      Munc18-1 null neurons, chromaffin cells and Munc18-1/-2 knockdown PC12 cells,
      allowing remarkable progress to be made in the structural/functional
      understanding of Munc18-1. In this review, we summarize these recent advances and
      attempt to propose an updated model of the pleiotropic functions of Munc18-1 in
      neuroexocytosis.

PMID- 20681956
TI  - Prognostic utility of spontaneous erythroid colony formation and JAK2 mutational
      analysis for thrombotic events in essential thrombocythaemia.
AB  - BACKGROUND: Thrombotic events in essential thrombocythaemia (ET) are difficult to
      predict with current risk stratification based on age and prior history of
      thrombosis. AIMS: We aimed to assess the predictive value of the JAK2 V617F
      mutation (JAK2) and spontaneous erythroid colony (SEC) growth for the development
      of thrombotic events post diagnosis in patients with ET. METHODS: Consecutive
      patients with ET were retrospectively identified, and clinical and laboratory
      correlates were evaluated. Thrombotic events were categorized according to their
      occurrence at or prior to diagnosis (prior thrombosis), and any time post
      diagnosis of ET (subsequent thrombosis). JAK2 analysis was performed by allele
      specific PCR on whole blood or bone marrow. RESULTS: A total of 62 patients was
      identified, median age 63 years; 67% (41/61) JAK2-positive and 47% (25/53) SEC
      positive. Median follow-up was 33 months (range, 1 to 137). JAK2-positive
      patients showed a trend to increased prior thrombosis (27% vs 5%, P= 0.08), and a
      significant increase in the development of subsequent thrombosis (5-year event
      rate 31% vs 6%, P= 0.04), which persisted when stratified for a history of prior
      thrombosis (P= 0.04). Survival was not affected by JAK2 status. The SEC assay
      predicted an increased rate of baseline thrombosis (16% vs 0%, P= 0.04), but was
      not found to be predictive of any subsequent thrombotic events. CONCLUSIONS:
      Patients with ET who are JAK2-positive by whole blood allele-specific PCR appear
      to be at increased risk of thrombotic complications, which is independent of a
      prior history of thrombosis.

PMID- 20681957
TI  - IVI epoprostenol as salvage therapy in pulmonary arterial hypertension: an
      Australian perspective.
AB  - BACKGROUND: IVI epoprostenol is the only therapy for pulmonary arterial
      hypertension (PAH) with a randomized controlled trial demonstrating improved
      survival, when used as first-line monotherapy. In Australia it is used as salvage
      therapy for those failing treatment with other targeted therapies or presenting
      in World Health Organization functional class (FC) IV. AIMS: Report experience
      with IVI epoprostenol, administered as salvage therapy for the treatment of
      adults with PAH in a single Australian PAH centre. METHODS: Retrospective case
      series of all patients commenced on IVI epoprostenol for PAH, between 2002 and
      2010. Review of case notes with collection of data at baseline and after
      treatment, including FC, 6-min walk test (6MWT), right ventricular systolic
      pressure (RVSP) on echocardiogram, patient survival and treatment complications.
      Change in indices was assessed using the Wilcoxon Sign Rank Test and is expressed
      as median (inter-quartile range). RESULTS: A total of 23 patients was included.
      Treatment was generally well tolerated with few major complications. At the end
      of the study period, nine patients were successfully bridged to transplant, five
      had a sustained response to IVI epoprostenol, six had an incomplete response but
      were clinically stabilized, two died awaiting transplant and one died who was not
      a candidate for transplantation. Overall, when measured at best level post
      initiation of IVI epoprostenol, there were significant improvements in FC -1 [0
      to -1] (P < 0.0001), 6MWT (m) +117 [70-264] (P= 0.002) and RVSP (mmHg) -7.0 [4.0
      to -45] (P= 0.03). CONCLUSION: Findings support efficacy of epoprostenol as
      salvage therapy for patients with PAH.

PMID- 20681958
TI  - Preliminary evaluation of the prevalence of falls, pain and urinary incontinence
      in remote living Indigenous Australians over the age of 45 years.
AB  - AIMS: To report on the prevalence of falls, urinary incontinence, pain and
      associated factors in remote living Indigenous Australians over the age of 45
      years. METHODS: A cross-sectional, semi-purposeful sample of 363 indigenous men
      and women aged over 45 years living in six remote communities and one town in
      Kimberley, Australia. Participants were assessed for self- or informant-reported
      rates of falls, urinary incontinence and pain. RESULTS: The prevalence of self-
      or informant-reported falls was 31% (95% CI 25.3, 36.7), pain 55% (95% CI 47.4,
      62.6) and urinary incontinence 9% (95% CI 5.9, 12.1%). Associations with falls
      after adjustment for age, sex and education included alcohol use (OR 2.4, 95% CI
      1.4, 4.2), stroke (OR 2.4, 95% CI 1.1, 5.0), epilepsy (OR 3.5, 95% CI 1.1, 11.6),
      head injury (OR 2.1, 95% CI 1.3, 3.3) and poor hearing (OR 2.5, 95% CI 1.4, 4.1);
      for urinary incontinence epilepsy (OR 6.0, 95% CI 1.7, 21.2) and stroke (OR 16.7,
      95% CI 6.0, 46.3); and for pain, poor hearing (OR 1.9, 95% CI 1.0, 3.3) and
      female sex (OR 1.8, 95% CI 1.2, 2.7). CONCLUSIONS: Falls, urinary incontinence
      and pain are common and reported for the first time in older indigenous people
      living in remote regions. The presence of these syndromes in ages over 45 may be
      due to accumulation of health insults during the life course.

PMID- 20681959
TI  - Managing acute medical admissions: a survey of acute medical services and medical
      assessment and planning units in New Zealand.
AB  - AIMS: To determine the current provision of acute medical services, including the
      development of medical assessment and planning units (MAPUs), by district health
      boards (DHBs) throughout New Zealand (NZ). METHODS: A questionnaire-based survey
      about organisation of acute medical services and establishment of MAPUs was sent
      to all 21 DHBs in NZ. RESULTS: All 21 DHBs responded. Seven DHBs serving 42% of
      the population have established MAPUs since 2003 and a further six have plans to
      do so over the next 3 years, potentially expanding service to 73% of the NZ
      population. All seven current MAPUs are in close proximity to and accept patients
      directly from emergency departments. Each MAPU has a documented target length of
      stay, four units have referral protocols, five provide guidelines for management
      of common medical emergencies and five routinely audit unit performance. Five
      MAPUs have cardiac monitored beds and isolation rooms. Rapid access is available
      to computed tomography scanning (six units), ultrasound (five) and
      echocardiography (four). Two units have no nominated physician leadership and two
      lack dedicated therapy resources. General physicians are involved in provision of
      acute medical services in 20 of 21 DHBs. CONCLUSIONS: Medical assessment and
      planning units have become an important component of acute medical service
      provision in NZ. The established units largely comply with Australasian
      recommendations, although important deficiencies exist. Training of physicians
      must combine the needs of acute medical patients and clinical roles of physicians
      within MAPUs with local DHB requirements for services to be most effective.

PMID- 20681960
TI  - Death, dependency and health status 90 days following hospital admission for
      acute stroke in NSW.
AB  - BACKGROUND: Stroke is an Australian health priority area causing considerable
      levels of disability. We report 90-day outcomes for a cohort of acute stroke
      patients in New South Wales (NSW), Australia prior to randomization to a large
      cluster randomized controlled trial (CRCT), the Quality in Acute Stroke Care
      (QASC) trial. AIMS: This paper describes prospectively collected, 90-day outcome
      data for a cohort of NSW stroke patients, providing pre-intervention data for the
      QASC trial. METHODS: A consecutive sample of patients from acute stroke units in
      NSW was recruited. We measured patient death, disability (modified Rankin Score
      (mRS)), dependency (Barthel Index (BI)) and Health Status (Medical Outcomes Short
      Form Health Survey (SF-36)) 90 days post-hospital admission. We also collected
      self-reported healthcare utilization and patient satisfaction with health
      professionals' advice and management to reduce risk of subsequent stroke.
      RESULTS:   Ninety-day outcome data were obtained for 687 patients, of which, 335
      (49%) had an mRS >=2; 44 patients (6.4%) had died. For the 643 surviving
      patients, the mean BI was 87.2 (SD 21.9) and the mean scores for SF-36 Physical
      Component Summary score and Mental Component Summary score were 46.2 (SD 10.1)
      and 46.3 (SD 12.6) respectively. CONCLUSIONS: In this pre-intervention cohort of
      selected acute stroke inpatients, stroke severity was mild to moderate and
      subsequent clinical outcomes were favourable in the majority. The findings from
      this study provide a comprehensive description of 90-day health outcomes of
      patients who have experienced a mild-moderate stroke managed in stroke care units
      across metropolitan NSW and provide valuable data to inform the subsequent
      cluster trial.

PMID- 20681961
TI  - Clinical audit of antiphospholipid antibody testing in tertiary practice: towards
      improved relevance in thrombophilia investigations.
AB  - BACKGROUND: The antiphospholipid syndrome (APS) is an autoimmune condition
      characterised by vascular thromboses and/or pregnancy morbidity. Diagnosis of APS
      typically requires laboratory evidence of antiphospholipid antibodies (aPL).
      Depending on their clinical presentation, affected individuals might be seen by a
      variety of clinical specialities. AIM: To evaluate clinical ordering patterns for
      aPL/APS at a tertiary level public facility. METHODS: We performed an audit of
      internal clinical requests for aPL tests at our institution for a 6-month period.
      RESULTS: We identified a wide variety of clinical ordering background for aPL, of
      predominantly obstetric (72/268; 26.9%) or thrombophilic (78/268; 29.1%)
      patients. Only 11/268 samples (4.1%) were positive for lupus anticoagulant (LA)
      and 14/268 (5.2%) were positive for anticardiolipin antibody (aCL). The
      percentage of aCL positivity in the LA-positive group was 46% (5/11). None of the
      72 obstetric patients tested was identified to have aPL. Of the 11 LA-positive
      patients, the reasons identified for testing comprised: prolonged Activated
      Partial Thromboplastin Time (assay) (n= 3), thrombosis (n= 3), APS (n= 2),
      systemic lupus erythematosus (n= 2), vasculitis (n= 1). CONCLUSION: We determined
      a wide variety of clinical ordering background for aPL at a tertiary level
      institution, with an overall low rate (<10%) of aPL positivity among a hospital
      population of predominantly obstetric or thrombophilic patients. That no positive
      obstetric aPL cases were identified suggests local clinical ordering guidelines
      may need review, as also potentially practised at other institutions. We also
      observed a moderate rate (46%) of coincidence of aCL and LA, in agreement with
      guidelines indicating that multiple tests are required to identify APS.

PMID- 20681962
TI  - Potentially avoidable surgery in inflammatory bowel disease: what proportion of
      patients come to resection without optimal preoperative therapy? A guidelines
      based audit.
AB  - BACKGROUND: Recently, promulgated inflammatory bowel disease (IBD) guidelines
      seek to decrease the need for surgery by improving disease control. However,
      resection rates remain static. AIMS: We therefore sought to determine the
      proportion of patients coming to surgery where preoperative management was not
      optimal according to guidelines. METHODS: Case notes of all patients with
      resection surgery for IBD from January 2007 to March 2008 at a metropolitan
      teaching hospital were retrospectively reviewed. Judgement was made as to whether
      preoperative management was optimal or suboptimal depending on whether it met
      guidelines. RESULTS: A total of 22 subjects with IBD-related resections were
      identified (15 males and seven females). In total, 17 had Crohn's disease (CD)
      (11 males) and five ulcerative colitis (UC) (four males). There were 10 smokers
      (nine CD and one UC). The two most common indications for surgery were
      inflammatory mass/abscess (n= 8) and refractory to medical therapy (n= 7). While
      all patients with known IBD (20/22) had seen a gastroenterologist in the past,
      five known IBD patients had resections undertaken without preoperative
      gastroenterologist input. Overall preoperative management was judged as optimal
      in only (9/22) 41%. Of those whose therapy did not meet guidelines (n= 13), five
      had azathioprine at doses <2 mg/kg, one declined therapy and nine with CD were
      current smokers. CONCLUSIONS: Over 50% of IBD resection patients had suboptimal
      preoperative management, with sub-therapeutic thiopurine dosing and smoking in CD
      the main problems. Thus, there are significant gains to be made with better use
      of standard therapies, as it appears that ~50% of resection surgery was
      'potentially avoidable'.

PMID- 20681963
TI  - Experimental study of bite mark injuries by digital analysis.
AB  - This study was based on a morphometric analysis of bite marks starting from the
      quantitative definition of the anterior teeth by the geometric acquisition of the
      "injuries," using bite marks impressed on pig skin and plastic. Each mark was
      photographed and acquired. A dedicated program automatically supplied the values
      of the shape factors and the areas of the pattern geometric figures. The values
      obtained for the homologous samples were compared to the heterologous values.
      Statistical comparison was made of the sets by linear regression, determining the
      correlation coefficient and the determination coefficient for each value. Results
      showed only 4.8% and 2% of overlap between homologous and heterologous values.
      This study was carried out in attempting to quantitatively define the anterior
      teeth of the human dentition and the procedure described and the results obtained
      support the advantage of morphometric studies and computer-aided programs in this
      study of bite marks.

PMID- 20681964
TI  - A new method for determination of postmortem interval: citrate content of bone.
AB  - Few accurate methods exist currently to determine the time since death
      (postmortem interval, PMI) of skeletonized human remains found at crime scenes.
      Citrate is present as a constituent of living human and animal cortical bone at
      very uniform initial concentration (2.0 +/- 0.1 wt %). In skeletal remains found
      in open landscape settings (whether buried or not), the concentration of citrate
      remains constant for a period of about 4 weeks, after which it decreases linearly
      as a function of log(time). The upper limit of the dating range is about 100
      years. The precision of determination decreases slightly with age. The rate of
      decrease appears to be independent of temperature or rainfall but drops to zero
      for storage temperature <0 degrees C.

PMID- 20681965
TI  - Trace element analysis of rough diamond by LA-ICP-MS: a case of source
      discrimination?
AB  - Current profiling of rough diamond source is performed using different physical
      and/or morphological techniques that require strong knowledge and experience in
      the field. More recently, chemical impurities have been used to discriminate
      diamond source and with the advance of laser ablation-inductively coupled plasma
      mass spectrometry (LA-ICP-MS) empirical profiling of rough diamonds is possible
      to some extent. In this study, we present a LA-ICP-MS methodology that we
      developed for analyzing ultra-trace element impurities in rough diamond for
      origin determination ("profiling"). Diamonds from two sources were analyzed by LA
      ICP-MS and were statistically classified by accepted methods. For the two diamond
      populations analyzed in this study, binomial logistic regression produced a
      better overall correct classification than linear discriminant analysis. The
      results suggest that an anticipated matrix match reference material would improve
      the robustness of our methodology for forensic applications.

PMID- 20681966
TI  - A review of forensic science higher education programs in the United States:
      bachelor's and master's degrees.
AB  - As the number of forensic science programs offered at higher education
      institutions rises, and more students express an interest in them, it is
      important to gain information regarding the offerings in terms of courses,
      equipment available to students, degree requirements, and other important aspects
      of the programs. A survey was conducted examining the existing bachelor's and
      master's forensic science programs in the U.S. Of the responding institutions,
      relatively few were, at the time of the survey, accredited by the forensic
      science Education Programs Accreditation Commission (FEPAC). In general, the
      standards of the responding programs vary considerably primarily in terms of
      their size and subjects coverage. While it is clear that the standards for the
      forensic science programs investigated are not homogeneous, the majority of the
      programs provide a strong science curriculum, faculties with advanced degrees,
      and interesting forensic-oriented courses.

PMID- 20681967
TI  - A new microtitre plate screening method for evaluating the viability of aerobic
      respiring bacteria in high surface biofilms.
AB  - AIMS: It is difficult to determine the effects of bactericidal compounds against
      bacteria in a biofilm because classical procedures for determining cell viability
      require several working days, multiple complicated steps and are frequently only
      applicable to cells in suspension. We attempt to develop a compact, inexpensive
      and versatile system to measure directly the extent of biofilm formation from
      water systems and to determine the viability of respiring bacteria in high
      surface biofilms. METHODS AND RESULTS: It has been reported that the reduction of
      tetrazolium sodium salts, such as XTT (sodium 3,3'-[1-[(phenylamino)carbonyl]-3,4
      tetrazolium]Bis(4-methoxy)-6-nitro)benzene sulfonic acid hydrate), during active
      bacterial metabolism can be incorporated into a colorimetric method for
      quantifying cell viability. XTT is reduced to a soluble formazan compound during
      bacterial aerobic metabolism such that the amount of formazan generated is
      proportional to the bacterial biomass. CONCLUSIONS: We show here, for the first
      time, that this colorimetric approach can be used to determine the metabolic
      activity of adherent aerobic bacteria in a biofilm as a measure of cell
      viability. This technique has been used to estimate viability and proliferation
      of bacteria in suspension, but this is the first application to microbial
      communities in a real undisturbed biofilm. SIGNIFICANCE AND IMPACT OF THE STUDY:
      This simple new system can be used to evaluate the complex biofilm community
      without separating the bacteria from their support. Thus, the results obtained by
      this practice may be more representative of the circumstances in a natural
      system, opening the possibility to multiple potential applications.

PMID- 20681968
TI  - Detection and quantification of methicillin-resistant Staphylococcus aureus
      (MRSA) clones in retail meat products.
AB  - AIMS: The objective of the study was to determine the prevalence of methicillin
      resistant Staphylococcus aureus (MRSA) contamination of retail meat and to
      determine the level of contamination. METHODS AND RESULTS: Pork (pork chops and
      ground pork), ground beef and chicken (legs, wings and thighs) were purchased at
      retail outlets in four Canadian provinces and tested for the presence of
      methicillin-resistant Staph. aureus using qualitative and quantitative methods.
      MRSA was isolated from 9.6% of pork, 5.6% of beef and 1.2% of chicken samples (P
      = 0.0002). Low levels of MRSA were typically present, with 37% below the
      detection threshold for quantification and <100 CFU g(-1) present in most
      quantifiable samples. All isolates were classified as Canadian epidemic MRSA-2
      (CMRSA-2) by pulsed field gel electrophoresis (PFGE), with two different PFGE
      subtypes, and were spa type 24/t242. CONCLUSIONS: MRSA contamination of retail
      meat is not uncommon. While CMRSA-2, a human epidemic clone, has been found in
      pigs in Canada, the lack of isolation of livestock-associated ST398 was
      surprising. SIGNIFICANCE AND IMPACT OF THE STUDY: The relevance of MRSA
      contamination of meat is unclear but investigation is required because of the
      potential for exposure from food handling. Sources of contamination require
      investigation because these results suggest that human or animal sources could be
      involved.

PMID- 20681969
TI  - The synergy of honokiol and fluconazole against clinical isolates of azole
      resistant Candida albicans.
AB  - AIMS: To evaluate the interaction of fluconazole (FLC) and honokiol (HNK) in
      vitro and vivo against azole-resistant (azole-R) clinical isolates of Candida
      albicans. METHODS AND RESULTS: A checkerboard microdilution method was used to
      study the in vitro interaction of FLC and HNK in 24 azole-R clinical isolates of
      C. albicans. In vivo antifungal activity was performed to further analyse the
      interaction between FLC and HNK. In the in vitro study, synergism was observed in
      all 24 FLC-resistant strains tested as determined by fractional inhibitory
      concentration index (FICI), and in 22 strains by Delta E models. No antagonistic
      activity was observed in any of the strains tested. These positive interactions
      were also confirmed by using the time-killing test for the selected strain C.
      albicans YL371, which shows strong susceptible to the combination of HNK and FLC.
      In the in vivo study, the mice with candidiasis were treated successfully by a
      combination therapy of HNK with FLC, the results showed a decrease of the colony
      forming unit in infected and treated animals compared to the controls, at the
      conditions of the treatment used in this study. CONCLUSIONS: Synergistic activity
      of HNK and FLC against clinical isolates of FLC-resistant C. albicans was
      observed in vitro and in vivo. SIGNIFICANCE AND IMPACT OF THE STUDY: This report
      might provide a potential therapeutic method to overcome the problem of drug
      resistance in C. albicans.

PMID- 20681970
TI  - Zygomatic salivary mucocoele as a postoperative complication following caudal
      hemimaxillectomy in a dog.
AB  - Zygomatic mucocoele is reported as a postoperative complication occurring
      secondary to a caudal hemimaxillectomy in a two-year-old Labrador retriever. The
      dog was presented with a history of a rapidly growing oral mass, identified as a
      soft tissue sarcoma. A caudal hemimaxillectomy via an intraoral approach was
      performed as treatment for local control of the oral mass. Fifteen days
      postoperatively, periorbital swelling and exophthalmos developed on the
      ipsilateral side. The degree of swelling progressed and was identified by
      computed tomography, ultrasound and cytology as a salivary mucocoele. Zygomatic
      sialoadenectomy was performed via a modified lateral approach with zygomatic
      osteotomy. A small amount of discharge persisted from the surgical site but
      gradually resolved. Recurrence of the periorbital swelling and exophthalmos was
      noted 25 days later and further surgery was performed to excise residual salivary
      tissue. Adjuvant radiotherapy was performed, however local recurrence of the oral
      mass was identified 5 months postoperatively and the patient subsequently
      euthanased. Salivary mucocoele has been cited as a possible postoperative
      complication following maxillectomy and mandibulectomy procedures; however to the
      authors' knowledge, only one previous case report exists in the literature. The
      current case documents a zygomatic salivary mucocoele occurring subsequent to
      caudal hemimaxillectomy.

PMID- 20681971
TI  - Hydrogen peroxide is involved in the sclerotial differentiation of filamentous
      phytopathogenic fungi.
AB  - AIMS: The purpose of this study was to investigate the role of H(2) O(2) and the
      related oxidative stress markers catalase (CAT) and lipid peroxidation in the
      sclerotial differentiation of the phytopathogenic filamentous fungi Sclerotium
      rolfsii, Sclerotinia minor, Sclerotinia sclerotiorum and Rhizoctonia solani.
      METHODS AND RESULTS: Using the H(2) O(2) -specific scopoletin fluorometric assay
      and the CAT-dependent H(2) O(2) consumption assays, it was found that the
      production rate of intra/extracellular H(2) O(2) and CAT levels in the
      sclerotiogenic fungi were significantly higher and lower, respectively, than
      those of their nondifferentiating counterpart strains. They peaked in the
      transition between the undifferentiated and the differentiated state of the
      sclerotiogenic strains, suggesting both a cell proliferative and differentiative
      role. In addition, the indirect indicator of oxidative stress, lipid
      peroxidation, was substantially decreased in the nondifferentiating strains.
      CONCLUSIONS: These findings suggest that the differentiative role of H(2) O(2) is
      expressed via induction of higher oxidative stress in the sclerotiogenic
      filamentous phytopathogenic fungi. SIGNIFICANCE AND IMPACT OF THE STUDY: This
      study shows that the direct marker of oxidative stress H(2) O(2) is involved in
      the sclerotial differentiation of the phytopathogenic filamentous fungi S.
      rolfsii, S. minor, S. sclerotiorum and R. solani, which could have potential
      biotechnological implications in terms of developing antifungal strategies by
      regulating intracellular H(2) O(2) levels.

PMID- 20681972
TI  - Construction and evaluation of self-cloning bottom-fermenting yeast with high
      SSU1 expression.
AB  - AIM: To construct a self-cloning brewer's yeast that can minimize the
      unfavourable flavours caused by oxidation and certain kinds of sulfur compounds.
      METHODS AND RESULTS: DNA fragments of a high-expression promoter from the TDH3
      gene originating from Saccharomyces cerevisiae were integrated into the promoter
      regions of the S. cerevisiae-type and Saccharomyces bayanus-type SSU1 genes of
      bottom-fermenting brewer's yeast. PCR and sequencing confirmed the TDH3 promoter
      was correctly introduced into the SSU1 regions of the constructed yeasts, and no
      foreign DNA sequences were found. Using the constructed yeasts, the concentration
      of sulfite in fermenting wort was higher when compared with the parent strain. In
      addition, the concentrations of hydrogen sulfide, 3-methyl-2-buten-1-thiol (MBT)
      and 2-mercapto-3-methyl-1-butanol (2M3MB) were lower when compared with the
      parent strain. CONCLUSION: We successfully constructed a self-cloning brewer's
      yeast with high SSU1 expression that enhanced the sulfite-excreting ability and
      diminished the production ability of hydrogen sulfide, MBT and 2M3MB.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The self-cloning brewer's yeast with high
      SSU1 expression would contribute to the production of superior quality beer with
      a high concentration of sulfite and low concentrations of hydrogen sulfide, MBT
      and 2M3MB.

PMID- 20681973
TI  - Functional characterization of drought-responsive aquaporins in Populus
      balsamifera and Populus simonii*balsamifera clones with different drought
      resistance strategies.
AB  - We have characterized poplar aquaporins (AQPs) to investigate their possible
      functions in differential drought responses of Populus balsamifera and Populus
      simonii*balsamifera leaves. Plants were exposed to mild and severe levels of
      drought stress and to drought stress recovery treatment, and their responses were
      compared with well-watered controls. Compared with P. balsamifera, P.
      simonii*balsamifera used drought avoidance as the main drought resistance
      strategy, and rapidly reduced stomatal conductance in response to stress. This
      strategy is correlated with growth rate reductions. Eleven AQPs were
      transcriptionally profiled in leaves from these experiments and five were
      functionally characterized for water channel activity. PIP1;3 and PIP2;5 were
      among the most highly expressed leaf AQPs that were responsive to drought.
      Expression of PIP1;3 and five other AQPs increased in response to drought in the
      leaves of P. simonii*balsamifera but not in P. balsamifera, suggesting a possible
      role of these AQPs in water redistribution in the leaf tissues. PIP2;5 was
      upregulated in P. balsamifera, but not in P. simonii*balsamifera, suggesting that
      this AQP supports the transpiration-driven water flow. Functional
      characterization of five drought-responsive plasma membrane intrinsic proteins
      (PIPs) demonstrated that three PIP2 AQPs (PIP2;2, PIP2;5, PIP2;7) functioned as
      water transporters in Xenopus laevis oocytes, while the two PIP1 AQPs (PIP1;2 and
      PIP1;3) did not, consistent with the notion that they may be functional only as
      heterotetramers.

PMID- 20681974
TI  - Transmembrane nine proteins in yeast and Arabidopsis affect cellular metal
      contents without changing vacuolar morphology.
AB  - Transmembrane nine (TM9) proteins are localized in the secretory pathway of
      eukaryotic cells and are involved in cell adhesion and phagocytosis. The
      mechanism by which TM9 proteins operate is, however, not well understood. Here we
      have utilized elemental profiling by inductively coupled plasma mass spectrometry
      (ICP-MS) to further investigate the physiological function of TM9 proteins.
      Cellular copper contents in Saccharomyces cerevisiae varied depending on the
      presence of TM9 homologues from both yeast and Arabidopsis thaliana. A yeast tmn1
      3 triple mutant lacking all three yeast endogenous TMNs showed altered metal
      homeostasis with a reduction in the cellular Cu contents to 25% of that in the
      wild-type. Conversely, when TMN1 was overexpressed in yeast, cellular Cu
      concentrations were more than doubled. Both Tmn1p-GFP and Tmn2p-GFP fusion
      proteins localized to the tonoplast. Yeast vacuolar biogenesis was not affected
      by the lack or presence of TM9 proteins neither in the tmn1-3 triple mutant nor
      in TM9 overexpressing strains. Heterologous expression in yeast of AtTMN7, a TM9
      homologue from Arabidopsis, affected Cu homeostasis similar to the overexpression
      of TMN1. In Arabidopsis, the two TM9 homologues AtTMN1 and AtTMN7 were
      ubiquitously expressed. AtTMN7 promoter constructs driving the expression of GFP
      showed elevated expression of AtTMN7 in the root elongation zone. It is concluded
      that TM9 homologues from S. cerevisiae and A. thaliana have the ability to affect
      the intracellular Cu balance. Tmn1p and Tmn2p operate from the yeast vacuolar
      membrane without influencing vacuolar biogenesis. A new physiological function of
      the TM9 family coupled to vacuolar Cu homeostasis is proposed.

PMID- 20681975
TI  - Epibrassinolide induces changes in indole-3-acetic acid, abscisic acid and
      polyamine concentrations and enhances antioxidant potential of radish seedlings
      under copper stress.
AB  - In the present study, the effects of epibrassinolide (EBL) on indole-3-acetic
      acid (IAA), abscisic acid (ABA) and polyamine (PA) tissue concentrations and
      antioxidant potential of 7-day-old Raphanus sativus L. cv. 'Pusa chetki'
      seedlings grown under Cu stress were investigated. EBL treatment alone or in
      combination with Cu enhanced free and bound IAA titers when compared with the
      metal alone. Modest increases in free and bound ABA contents were observed for
      EBL treatment alone. However, the combination of EBL with Cu caused major
      increases in both forms of ABA, over Cu alone. Among the PAs analyzed, only
      putrescine and cadaverine concentrations were enhanced by EBL treatment alone. By
      contrast, a significant decline in putrescine and spermine contents was found in
      seedlings treated with EBL plus Cu. EBL treatments alone or in combination with
      Cu enhanced activities of guaiacol peroxidase (EC1.11.1.7), catalase (EC
      1.11.1.6), superoxide dismutase (EC 1.15.1.1) and glutathione reductase (EC
      1.6.4.2) and protein contents in comparison with metal and control treatments. A
      major decrease in malondialdehyde content was also recorded for EBL treatments
      with or without Cu. An increase in phytochelatin content was also observed in
      seedlings treated with EBL alone or in combination with Cu. Major improvement in
      radical scavenging activities, as attested by the antioxidant activity assay
      using DPPH (1,1-diphenylpicrylhydrazyl), and elevated deoxyribose and reducing
      powers, along with increased contents of ascorbic acid, total phenols and
      proline, also suggest a major influence of EBL application in mitigating copper
      induced oxidative stress in radish seedlings.

PMID- 20681977
TI  - Manufacture of red cells in additive solution from whole blood refrigerated for 5
      days or remanufactured from red cells stored in plasma.
AB  - BACKGROUND AND OBJECTIVES: To investigate methods for the production of red cell
      concentrates (RCC) in saline, adenine, glucose and mannitol (SAG-M), from whole
      blood or red cells stored in plasma for 5 or 6 days and to provide evidence that
      exchange transfusion RCC in citrate phosphate dextrose (CPD) plasma or citrate,
      phosphate, dextrose, adenine (CPDA-1) plasma are of comparable quality. METHODS
      AND MATERIALS: Ten RCC in SAG-M were produced following the remanufacture of red
      cells in CPD plasma on day 5/6 or after 5 days hold as leucodepleted CPD whole
      blood. In addition, 10 RCC in CPD plasma and 9 in CPDA-1 plasma were stored
      without further processing. Units were assessed for red cell parameters including
      haemolysis, adenosine triphosphate (ATP), 2,3-diphosphoglycerate (2,3-DPG) and
      extracellular potassium. RESULTS: Units in SAG-M produced by remanufacture of RCC
      in plasma or by delayed manufacture of whole blood had comparable levels of
      haemolysis, ATP and 2,3-DPG. Furthermore, these units underwent biochemical
      changes similar to reference SAG-M units, with the exception of haemolysis which
      was greater at the end of shelf life and supernatant potassium which was lower
      following remanufacture. As expected, the decline in ATP was greater in red cells
      stored in CPD plasma compared with CPDA-1 plasma. In general, units in CPD plasma
      were of similar quality at day 28 compared to those in CPDA-1 plasma at day 35.
      CONCLUSIONS: RCC produced following the remanufacture of RCC in plasma or the
      delayed manufacture of whole blood are of acceptable in vitro quality and should
      be assigned the same shelf life as standard RCC in SAG-M.

PMID- 20681978
TI  - Rapidly growing orf in a renal transplant recipient: favourable outcome with
      reduction of immunosuppression and imiquimod.
AB  - Orf is a viral skin infection due to a poxvirus. It manifests as a nodule of the
      hands that heals spontaneously within 3-4 weeks, but may be persisting and
      difficult to treat in immunocompromised patients. Very few cases have been
      reported in transplant patients; therefore, management is not established. We
      report a renal transplant recipient with a rapidly growing orf which regressed
      after application of imiquimod and a reduction in immunosuppression without
      damage on his renal function. This case suggests that a rapidly growing orf in
      transplant patients behaves as an opportunistic infection and therefore
      minimization should be considered along with a topical treatment.

PMID- 20681979
TI  - Kidney dendritic cells in acute and chronic renal disease.
AB  - Dendritic cells are not only the master regulators of adaptive immunity, but also
      participate profoundly in innate immune responses. Much has been learned about
      their basic immunological functions and their roles in various diseases.
      Comparatively little is still known about their role in renal disease, despite
      their obvious potential to affect immune responses in the kidney, and immune
      responses that are directed against renal components. Kidney dendritic cells form
      an abundant network in the renal tubulointerstitium and constantly survey the
      environment for signs of injury or infection, in order to alert the immune system
      to the need to initiate defensive action. Recent studies have identified a role
      for dendritic cells in several murine models of acute renal injury and chronic
      nephritis. Here we summarize the current knowledge on the role of kidney
      dendritic cells that has been obtained from the study of murine models of renal
      disease.

PMID- 20681981
TI  - Distinct granuloma responses in C57BL/6J and BALB/cByJ mice in response to
      pristane.
AB  - Granuloma formation is an inflammatory response of the host against invading
      pathogens or indigestible substances. We generated mesenteric oil granulomas by
      injecting pristane into the peritoneal cavity (PC) of mice, and compared oil
      granuloma formation in the C57BL/6J and BALB/cByJ strains of mice. The formation
      and kinetics of oil granulomas were distinct between the two strains. In C57BL/6J
      mice, injected pristane induced oil granuloma formation at both the mesenteric
      centers (MG) and margins (SG). MG was resolving by 11 weeks, and SG persisted. In
      BALB/cByJ mice, MG developed slower but persisted longer than in C57BL/6J mice,
      and SG resolved sooner than in C57BL/6J mice. Injection of India ink revealed
      that phagocytes were localised mainly to the SG in C57BL/6J mice, but were
      located diffusely in both MG and SG of BALB/cByJ mice. SG cells expressed more
      monocyte chemotactic protein-1 (MCP-1) mRNA than MG cells in C57BL/6J mice, but
      there was no difference in MCP-1 expression between the MG and SG in BALB/cByJ
      mice. These observations suggest that the recruitment of inflammatory leucocytes
      under the direction of chemokines differentiates the patterns of granuloma
      responses to pristane in C57BL/6J and BALB/cByJ mice.

PMID- 20681980
TI  - Congenital ureteropelvic junction obstruction: human disease and animal models.
AB  - Ureteropelvic junction (UPJ) obstruction is the most frequently observed cause of
      obstructive nephropathy in children. Neonatal and foetal animal models have been
      developed that mimic closely what is observed in human disease. The purpose of
      this review is to discuss how obstructive nephropathy alters kidney histology and
      function and describe the molecular mechanisms involved in the progression of the
      lesions, including inflammation, proliferation/apoptosis, renin-angiotensin
      system activation and fibrosis, based on both human and animal data. Also we
      propose that during obstructive nephropathy, hydrodynamic modifications are early
      inducers of the tubular lesions, which are potentially at the origin of the
      pathology. Finally, an important observation in animal models is that relief of
      obstruction during kidney development has important effects on renal function
      later in adult life. A major short-coming is the absence of data on the impact of
      UPJ obstruction on long-term adult renal function to elucidate whether these
      animal data are also valid in humans.

PMID- 20681982
TI  - Calibrating divergence times on species trees versus gene trees: implications for
      speciation history of Aphelocoma jays.
AB  - Estimates of the timing of divergence are central to testing the underlying
      causes of speciation. Relaxed molecular clocks and fossil calibration have
      improved these estimates; however, these advances are implemented in the context
      of gene trees, which can overestimate divergence times. Here we couple recent
      innovations for dating speciation events with the analytical power of species
      trees, where multilocus data are considered in a coalescent context. Divergence
      times are estimated in the bird genus Aphelocoma to test whether speciation in
      these jays coincided with mountain uplift or glacial cycles. Gene trees and
      species trees show general agreement that diversification began in the Miocene
      amid mountain uplift. However, dates from the multilocus species tree are more
      recent, occurring predominately in the Pleistocene, consistent with theory that
      divergence times can be significantly overestimated with gene-tree based
      approaches that do not correct for genetic divergence that predates speciation.
      In addition to coalescent stochasticity, Haldane's rule could account for some
      differences in timing estimates between mitochondrial DNA and nuclear genes. By
      incorporating a fossil calibration applied to the species tree, in addition to
      the process of gene lineage coalescence, the present approach provides a more
      biologically realistic framework for dating speciation events, and hence for
      testing the links between diversification and specific biogeographic and geologic
      events.

PMID- 20681983
TI  - Genetics of incipient speciation in Drosophila mojavensis. III. Life-history
      divergence in allopatry and reproductive isolation.
AB  - We carried out a three-tiered genetic analysis of egg-to-adult development time
      and viability in ancestral and derived populations of cactophilic Drosophila
      mojavensis to test the hypothesis that evolution of these life-history characters
      has shaped premating reproductive isolation in this species. First, a common
      garden experiment with 11 populations from Baja California and mainland Mexico
      and Arizona reared on two host species revealed significant host plant X region
      and population interactions for viability and development time, evidence for host
      plant adaptation. Second, replicated line crosses with flies reared on both hosts
      revealed autosomal, X chromosome, cytoplasmic, and autosome X cactus influences
      on development time. Viability differences were influenced by host plants,
      autosomal dominance, and X chromosomal effects. Many of the F(1) , F(2) , and
      backcross generations showed evidence of heterosis for viability. Third, a QTL
      analysis of male courtship song and epicuticular hydrocarbon variation based on
      1688 Baja * mainland F(2) males also revealed eight QTL influencing development
      time differences. Mainland alleles at six of these loci were associated with
      longer development times, consistent with population-level differences. Eight G *
      E interactions were also detected caused by longer development times of mainland
      alleles expressed on a mainland host with smaller differences among Baja
      genotypes reared on the Baja host plant. Four QTL influenced both development
      time and epicuticular hydrocarbon differences associated with courtship success,
      and there was a significant QTL-based correlation between development time and
      cuticular hydrocarbon variation. Thus, the regional shifts in life histories that
      evolved once D. mojavensis invaded mainland Mexico from Baja California by
      shifting host plants were genetically correlated with variation in cuticular
      hydrocarbon-based mate preferences.

PMID- 20681984
TI  - Haldane's rule is extended to plants with sex chromosomes.
AB  - Haldane's rule is an empirical phenomenon that has been observed in animals with
      sex chromosomes. The rule states that the heterogametic sex (XY or ZW) will be
      "absent, rare, or sterile" following hybridization between two species. Despite
      the near ubiquity of Haldane's rule in animal hybridizations, it has not been
      documented in organisms other than animals. Here, we show evidence for both
      rarity and sterility in hybrid male but not female offspring in crosses between
      three dioecious plant species from the genus Silene with heteromorphic (XY) sex
      chromosomes. Our results are consistent with Haldane's rule, extending its
      applicability to plants with sex chromosomes.

PMID- 20681986
TI  - Neuropeptide Y and osteoblast differentiation--the balance between the neuro
      osteogenic network and local control.
AB  - Accumulating evidence has contributed to a novel view in bone biology: bone
      remodeling, specifically osteoblast differentiation, is under the tight control
      of the central and peripheral nervous systems. Among other players in this neuro
      osteogenic network, the neuropeptide Y (NPY) system has attracted particular
      attention. At the central nervous system level, NPY exerts its function in bone
      homeostasis through the hypothalamic Y2 receptor. Locally in the bone, NPY action
      is mediated by its Y1 receptor. Besides the presence of Y1, a complex network
      exists locally: not only there is input of the peripheral nervous system, as the
      bone is directly innervated by NPY-containing fibers, but there is also input
      from non-neuronal cells, including bone cells capable of NPY expression. The
      interaction of these distinct players to achieve a multilevel control system of
      bone homeostasis is still under debate. In this review, we will integrate the
      current knowledge on the impact of the NPY system in bone biology, and discuss
      the mechanisms through which the balance between central and the peripheral NPY
      action might be achieved.

PMID- 20681987
TI  - The alr2505 (osiS) gene from Anabaena sp. strain PCC7120 encodes a cysteine
      desulfurase induced by oxidative stress.
AB  - NifS-like cysteine desulfurases are widespread enzymes involved in the
      mobilization of sulfur from cysteine. The genome of the filamentous diazotrophic
      cyanobacterium Anabaena PCC 7120 contains four open reading frames potentially
      encoding NifS-like proteins. One of them, alr2505, belongs to the pkn22 operon,
      which enables Anabaena to cope with oxidative stress. The Alr2505 protein was
      purified and found to share all the features characteristic of cysteine
      desufurases. This is the first NifS-like enzyme to be functionally characterized
      in this bacterium. On the basis of the transcriptional profiling of all nifS-like
      genes in Anabaena, it is concluded that alr2505 is the only cysteine desulfurase
      encoding gene induced by oxidative stress. The function of Alr2505, which was
      termed OsiS, is discussed.

PMID- 20681988
TI  - Expression and secretion of interleukin-1beta, tumour necrosis factor-alpha and
      interleukin-10 by hypoxia- and serum-deprivation-stimulated mesenchymal stem
      cells.
AB  - To understand the potential paracrine roles of interleukin-1beta (IL-1beta),
      tumour necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10), the
      expression and secretion of these factors by rat bone marrow-derived mesenchymal
      cells stimulated by hypoxia (4% oxygen) and serum deprivation (hypoxia/SD) were
      investigated. We found that hypoxia/SD induced nuclear factor kappa Bp65
      dependent IL-1beta and TNF-alpha transcription. Furthermore, hypoxia/SD
      stimulated the translation of pro-IL-1beta and its processing to mature IL-1beta,
      although the translation of TNF-alpha was unchanged. Unexpectedly, the release of
      IL-1beta and TNF-alpha from hypoxia/SD-stimulated mesenchymal cells was
      undetectable unless ATP or lipopolysaccharide was present. This result suggests
      that IL-1beta and TNF-alpha are not responsible for the paracrine effects of
      mesenchymal cells under ischaemic conditions. We also found that hypoxia/SD
      induced the transcription and secretion of IL-10, which were significantly
      enhanced by lipopolysaccharide and the proteasomal inhibitor MG132. Moreover,
      both the conditioned medium from hypoxia/SD-stimulated mesenchymal cells (MSC-CM)
      and IL-10 efficiently inhibited cardiac fibroblast proliferation and collagen
      expression in vitro, suggesting that mesenchymal cell-secreted IL-10 prevents
      cardiac fibrosis in a paracrine manner under ischaemic conditions. Taken
      together, these findings may improve understanding of the cellular and molecular
      basis of the anti-inflammatory and paracrine effects of mesenchymal cells.

PMID- 20681989
TI  - Aspergillus nidulans alpha-galactosidase of glycoside hydrolase family 36
      catalyses the formation of alpha-galacto-oligosaccharides by transglycosylation.
AB  - The alpha-galactosidase from Aspergillus nidulans (AglC) belongs to a
      phylogenetic cluster containing eukaryotic alpha-galactosidases and alpha-galacto
      oligosaccharide synthases of glycoside hydrolase family 36 (GH36). The
      recombinant AglC, produced in high yield (0.65 g.L(-1) culture) as His-tag fusion
      in Escherichia coli, catalysed efficient transglycosylation with alpha-(1-->6)
      regioselectivity from 40 mm 4-nitrophenol alpha-d-galactopyranoside, melibiose or
      raffinose, resulting in a 37-74% yield of 4-nitrophenol alpha-D-Galp-(1-->6)-D
      Galp, alpha-D-Galp-(1-->6)-alpha-D-Galp-(1-->6)-D-Glcp and alpha-D-Galp-(1-->6)
      alpha-D-Galp-(1-->6)-D-Glcp-(alpha1-->beta2)-d-Fruf (stachyose), respectively.
      Furthermore, among 10 monosaccharide acceptor candidates (400 mm) and the donor 4
      nitrophenol alpha-D-galactopyranoside (40 mm), alpha-(1-->6) linked
      galactodisaccharides were also obtained with galactose, glucose and mannose in
      high yields of 39-58%. AglC did not transglycosylate monosaccharides without the
      6-hydroxymethyl group, i.e. xylose, L-arabinose, L-fucose and L-rhamnose, or with
      axial 3-OH, i.e. gulose, allose, altrose and L-rhamnose. Structural modelling
      using Thermotoga maritima GH36 alpha-galactosidase as the template and
      superimposition of melibiose from the complex with human GH27 alpha-galactosidase
      supported that recognition at subsite +1 in AglC presumably requires a hydrogen
      bond between 3-OH and Trp358 and a hydrophobic environment around the C-6
      hydroxymethyl group. In addition, successful transglycosylation of eight of 10
      disaccharides (400 mm), except xylobiose and arabinobiose, indicated broad
      specificity for interaction with the +2 subsite. AglC thus transferred alpha
      galactosyl to 6-OH of the terminal residue in the alpha-linked melibiose,
      maltose, trehalose, sucrose and turanose in 6-46% yield and the beta-linked
      lactose, lactulose and cellobiose in 28-38% yield. The product structures were
      identified using NMR and ESI-MS and five of the 13 identified products were
      novel, i.e. alpha-D-Galp-(1-->6)-D-Manp; alpha-D-Galp-(1-->6)-beta-D-Glcp-(1-->4)
      D-Glcp; alpha-D-Galp-(1-->6)-beta-D-Galp-(1-->4)-D-Fruf; alpha-D-Galp-(1-->6)-D
      Glcp-(alpha1-->alpha1)-D-Glcp; and alpha-D-Galp-(1-->6)-alpha-D-Glcp-(1-->3)-D
      Fruf.

PMID- 20681985
TI  - Reconstructing origins of loss of self-incompatibility and selfing in North
      American Arabidopsis lyrata: a population genetic context.
AB  - Theoretical and empirical comparisons of molecular diversity in selfing and
      outcrossing plants have primarily focused on long-term consequences of
      differences in mating system (between species). However, improving our
      understanding of the causes of mating system evolution requires ecological and
      genetic studies of the early stages of mating system transition. Here, we examine
      nuclear and chloroplast DNA sequences and microsatellite variation in a large
      sample of populations of Arabidopsis lyrata from the Great Lakes region of
      Eastern North American that show intra- and interpopulation variation in the
      degree of self-incompatibility and realized outcrossing rates. Populations show
      strong geographic clustering irrespective of mating system, suggesting that
      selfing either evolved multiple times or has spread to multiple genetic
      backgrounds. Diversity is reduced in selfing populations, but not to the extent
      of the severe loss of variation expected if selfing evolved due to selection for
      reproductive assurance in connection with strong founder events. The spread of
      self-compatibility in this region may have been favored as colonization
      bottlenecks following glaciation or migration from Europe reduced standing levels
      of inbreeding depression. However, our results do not suggest a single transition
      to selfing in this system, as has been suggested for some other species in the
      Brassicaceae.

PMID- 20681990
TI  - Understanding the population structure of North American patients with cystic
      fibrosis.
AB  - It is generally presumed that the cystic fibrosis (CF) population is relatively
      homogeneous, and predominantly of European origin. The complex ethnic make-up
      observed in the CF patients collected by the North American CF Modifier Gene
      Consortium has brought this assumption into question, and suggested the potential
      for population substructure in the three CF study samples collected from North
      America. It is well appreciated that population substructure can result in
      spurious genetic associations. To understand the ethnic composition of the North
      American CF population, and to assess the need for population structure
      adjustment in genetic association studies with North American CF patients, genome
      wide single-nucleotide polymorphisms on 3076 unrelated North American CF patients
      were used to perform population structure analyses. We compared self-reported
      ethnicity to genotype-inferred ancestry, and also examined whether geographic
      distribution and cystic fibrosis transmembrane regulator (CFTR) mutation type
      could explain the population structure observed. Although largely Caucasian, our
      analyses identified a considerable number of CF patients with admixed African
      Caucasian, Mexican-Caucasian and Indian-Caucasian ancestries. Population
      substructure was present and comparable across the three studies of the
      consortium. Neither geographic distribution nor CFTR mutation type explained the
      population structure. Given the ethnic diversity of the North American CF
      population, it is essential to carefully detect, estimate and adjust for
      population substructure to guard against potential spurious findings in CF
      genetic association studies. Other Mendelian diseases that are presumed to
      predominantly affect single ethnic groups may also benefit from careful analysis
      of population structure.

PMID- 20681991
TI  - Pseudoautosomal inheritance of Leri-Weill syndrome: what does it mean?
AB  - The short stature homeobox (SHOX) gene is located in the pseudoautosomal region 1
      of both sex chromosomes. Haploinsufficiency of SHOX leads to different phenotypes
      ranging from isolated short stature to Leri-Weill syndrome characterized by short
      stature, mesomelia and Madelung deformity. We describe a family with a SHOX
      deletion originally located on the Y chromosome and transmitted from father to
      daughter by crossover during meiosis. The male index patient presented with short
      stature, mesomelia and mild Madelung deformity. His father had a normal height
      but slightly disproportionate short legs. The sister of the index patient
      presented with marked Madelung deformity and normal height. A deletion of the
      SHOX gene was identified in the male index patient, his father and his sister.
      Metaphase fluorescence in situ hybridization (FISH) analyses showed a deletion of
      the SHOX gene on the Y chromosomes of the index patient and his father, and on
      the X chromosome of his sister, indicating that a meiotic crossover of the SHOX
      gene region between the X and Y chromosomes had occurred. The pseudoautosomal
      region 1 is a known recombination 'hot spot' in male meiosis. Published genetic
      maps indicate high recombination frequency of ~40% for SHOX in male meiosis
      leading to pseudoautosomal inheritance.

PMID- 20681992
TI  - Metabolic and target organ outcomes after total pancreatectomy: Mayo Clinic
      experience and meta-analysis of the literature.
AB  - INTRODUCTION: Total pancreatectomy (TP) has been associated with substantial
      metabolic abnormalities and poor glycaemic control limiting its use. Because data
      reported to date are limited, we evaluated outcomes related to the diabetes
      mellitus obligated by TP. METHODS: A case series study of all patients who
      underwent TP from 01/01/1985 to 12/31/2006 at Mayo Clinic was conducted. TP cases
      were summarized according to perioperative procedures, mortality and morbidity
      after TP. To complement this retrospective examination, a survey was developed to
      measure DM treatment modality, target organ failure and complications in patients
      alive in 2007. We performed a meta-analysis to compare our results with similar
      previous studies and provide overall estimates of outcomes. RESULTS: A total of
      141 cases were studied (97 malignant diseases, 44 benign diseases). The median
      survival was much less for malignant pathology (2.2 vs 8.7 years, Log rank P =
      0.0009). In 2007, there were 59 patients that were presumed alive and 47 (80%)
      responded to the survey. Mean HbA1c at last follow-up was 7.5% with 89% of
      respondents on a complex insulin programme (mean daily insulin requirement 35 +/-
      13 units). Episodic hypoglycaemia was experienced by 37 (79%); 15 (41%)
      experienced severe hypoglycaemia. In contrast, diabetic ketoacidosis developed in
      only 2 (4%). Target organ complications and chronic diarrhoea developed in 13
      patients (28%) each. CONCLUSION: The primary factor determining survival after TP
      is the aetiology necessitating TP, i.e. pancreatic malignancy. Most respondents
      used complex insulin programmes, but hypoglycaemia continues to be a problem.

PMID- 20681993
TI  - The relationship between reduced testosterone, stimulated growth hormone
      secretion and increased carotid intima-media thickness in obese men.
AB  - OBJECTIVE: Obesity is associated with reduced testosterone and growth hormone
      (GH). However, the interrelationship between these axes and their independent
      contributions to cardiovascular risk is unknown. The objectives of this study
      were to determine (1) the association between testosterone and GH in obesity, (2)
      whether excess adiposity mediates this association and (3) the relative
      contribution of reduced testosterone and GH to increased carotid intima-media
      thickness (cIMT) in obesity. DESIGN: Fifty obese men were studied with GH
      releasing hormone-arginine testing, and morning free testosterone (FT) was
      measured by equilibrium dialysis. Metabolic, anthropometric and cardiovascular
      risk indices, including cIMT were measured. Twenty-six normal weight men served
      as controls. RESULTS: Obese subjects demonstrated lower mean (+/-SEM) peak
      stimulated GH (5.9 +/- 0.6 vs 36.4 +/- 3.9 MUg/l; P < 0.0001) and FT (0.41 +/-
      0.03 vs 0.56 +/- 0.03 nmol/l; P = 0.0005) compared to controls. GH was
      significantly associated with FT (r = +0.44; P < 0.0001) and both were inversely
      related to visceral adipose tissue (VAT) (GH: r = -0.65; P < 0.0001; FT: r = 
      0.51; P < 0.0001). In multivariate regression analysis controlling for VAT, FT
      was no longer related to GH. Both GH and FT were associated with cIMT in
      univariate analysis. However, in multivariate modelling including traditional
      cardiovascular risk markers, GH (beta = 0.003; P = 0.04) but not FT (P = 0.35)
      was associated with cIMT. CONCLUSIONS: These results demonstrate a strong
      relationship between FT and GH in obesity and suggest that this relationship is
      more a function of excess adiposity rather than a direct relationship. While
      reduced FT and GH are both related to increased cIMT, the relationship with
      reduced GH remains significant controlling for reduced FT and traditional
      cardiovascular disease risk markers.

PMID- 20681994
TI  - A prospective study of the associations between 25-hydroxy-vitamin D, sarcopenia
      progression and physical activity in older adults.
AB  - OBJECTIVE: Low 25-hydroxyvitamin D (25OHD) levels may be associated with both
      sarcopenia (the age-related decline in muscle mass and function) and low physical
      activity (PA). Our objective was to describe prospective associations between
      25OHD, muscle parameters, and PA in community-dwelling older adults. DESIGN:
      Prospective, population-based study with a mean follow-up of 2.6 +/- 0.4 years.
      PATIENTS: Six hundred and eighty-six community-dwelling older adults (49% women;
      mean +/- SD 62 +/- 7 years old). MEASUREMENTS: Appendicular lean mass percentage
      (%ALM) and body fat assessed by Dual-energy X-ray Absorptiometry, leg strength by
      dynamometer, leg muscle quality (LMQ), PA assessed by pedometer, self-reported
      sun exposure by questionnaire, and serum 25OHD measured by radioimmunoassay.
      RESULTS: Participants with 25OHD <=50 nM had lower mean %ALM, leg strength, LMQ
      and PA (all P < 0.05). As a continuous function, baseline 25OHD was a positive
      independent predictor of change in leg strength (beta = 5.74 kg, 95% CI 0.65,
      10.82) and LMQ (beta = 0.49 kg/kg, 95% CI 0.17, 0.82). Also, change in 25OHD was
      positively predicted by baseline %ALM (beta = 2.03 pM/p.a., 95% CI 0.44, 3.62)
      leg strength (beta = 0.30 pM/p.a., 95% CI 0.06, 0.53), LMQ (beta = 4.48 pM/p.a.,
      95% CI 0.36, 8.61) and PA (beta = 2.63 pM/p.a., 95% CI 0.35, 4.92) after
      adjustment for sun exposure and body fat. CONCLUSIONS: 25OHD may be important for
      the maintenance of muscle function, and higher skeletal muscle mass and function
      as well as general PA levels may also be beneficial for 25OHD status, in
      community-dwelling older adults.

PMID- 20681995
TI  - Evaluation of pituitary function after traumatic brain injury in childhood.
AB  - OBJECTIVES: Post-traumatic hypopituitarism is well described amongst adult
      traumatic brain injury (TBI) survivors. We aimed to determine the prevalence and
      clinical significance of pituitary dysfunction after head injury in childhood.
      DESIGN: Retrospective exploratory study. PATIENTS: 33 survivors of accidental
      head injury (27 boys). Mean (range) age at study was 13.4 years (5.4-21.7 years)
      and median (range) interval since injury 4.3 years (1.4-7.8 years). Functional
      outcome at study: 15 good recovery, 16 moderate disability, two severe
      disability. MEASUREMENTS: Early morning urine osmolality and basal hormone
      evaluation were followed by the gonadotrophin releasing hormone (GnRH) and
      insulin tolerance (n = 25) or glucagon tests (if previous seizures, n = 8).
      Subjects were not primed. Head injury details were extracted from patient
      records. RESULTS: No subject had short stature (mean height SD score +0.50, range
      -1.57 to +3.00). Suboptimal GH responses (<5 MUg/l) occurred in six peri-pubertal
      boys (one with slow growth on follow-up) and one postpubertal adolescent (peak GH
      3.2 MUg/l). Median peak cortisol responses to insulin tolerance or glucagon tests
      were 538 and 562 nm. Nine of twenty-five and two of eight subjects had suboptimal
      responses, respectively, two with high basal cortisol levels. None required
      routine glucocorticoid replacement. In three, steroid cover was recommended for
      moderate/severe illness or injury. One boy was prolactin deficient. Other basal
      endocrine results and GnRH-stimulated LH and FSH were appropriate for age, sex
      and pubertal stage. Abnormal endocrine findings were unrelated to the severity or
      other characteristics of TBI or functional outcome. CONCLUSIONS: No clinically
      significant endocrinopathy was identified amongst survivors of accidental
      childhood TBI, although minor pituitary hormone abnormalities were observed.

PMID- 20681996
TI  - Hippocampus development and function: role of epigenetic factors and implications
      for cognitive disease.
AB  - The hippocampus is a primary region of the brain controlling the formation of
      memories and learned behaviours. The ability to learn or form a memory requires a
      neuron to translate a transient signal into gene expression changes that have a
      long-lasting effect on synapse activity and connectivity. Numerous studies over
      the past decade have detailed changes in epigenetic modifications under various
      learning paradigms to support a role for chromatin remodelling in these
      processes. Moreover, the identification of mutations in epigenetic regulators as
      the cause of mental retardation or intellectual disability (MR/ID) disorders
      further strengthens their importance to learning and memory. Animal models for
      many of these disorders are emerging and advancing our understanding of the
      molecular mechanisms linking epigenetic regulation and cognitive function. Here,
      we review how chromatin remodelling proteins implicated in MR/ID contribute to
      the development of the hippocampus and memory formation.

PMID- 20681997
TI  - Clinical, biochemical and molecular characterization of peroxisomal diseases in
      Arabs.
AB  - Peroxisomes are single membrane-bound cellular organelles that carry out critical
      metabolic reactions perturbation of which leads to an array of clinical
      phenotypes known as peroxisomal disorders (PD). In this study, the largest of its
      kind in the Middle East, we sought to comprehensively characterize these rare
      disorders at the clinical, biochemical and molecular levels. Over a 2-year
      period, we have enrolled 17 patients representing 16 Arab families. Zellweger
      spectrum phenotype was observed in 12 patients and the remaining 5 had the
      rhizomelic chondrodysplasia punctata phenotype. We show that homozygosity mapping
      is a cost-effective strategy that enabled the identification of the underlying
      genetic defect in 100% of the cases. The pathogenic nature of the mutations
      identified was confirmed by immunofluorescence and complementation assays. We
      confirm the genetic heterogeneity of PD in our population, expand the pool of
      pathogenic alleles and draw some phenotype/genotype correlations.

PMID- 20681998
TI  - Novel missense mutations and unexpected multiple changes of RYR1 gene in 75
      malignant hyperthermia families.
AB  - Malignant hyperthermia (MH) is an autosomal dominant pharmacogenetic disorder of
      skeletal muscle characterized by disturbance of intracellular calcium homeostasis
      in the sarcoplasmic reticulum. Mutations of the ryanodine receptor 1 (RYR1) gene
      account for most cases, with some studies claiming up to 86% of mutations in this
      locus. However, RYR1 gene is large and variants are common even in the normal
      population. We examined 54 families with MH susceptibility and 21 diagnosed with
      equivocal MH. Thirty-five were selected for an anesthetic reaction, whereas the
      remainder for hyperCKemia. In these, we studied all 106 exons of the RYR1 gene.
      When no mutation was found, we also screened: sodium channel voltage-gated, type
      IV alpha subunit (SCN4A), calcium channel voltage-dependent, L type, alpha 1S
      subunit (CACNA1S), and L-type voltage-gated calcium channel alpha 2/delta-subunit
      (CACNL2A). Twenty-nine different RYR1 mutations were discovered in 40 families.
      Three other MH genes were tested in negative cases. Fourteen RYR1 amino acid
      changes were novel, of which 12 were located outside the mutational 'hot spots'.
      In two families, the known mutation p.R3903Q was also observed in malignant
      hyperthermia-nonsusceptible (MHN) individuals. Unexpectedly, four changes were
      also found in the same family and two in another. Our study confirms that MH is
      genetically heterogeneous and that a consistent number of cases are not due to
      RYR1 mutations. The discordance between in vitro contracture test status and the
      presence of a proven causative RYR1 mutation suggests that the penetrance may
      vary due to as yet unknown factors.

PMID- 20681999
TI  - Increasing hematopoietic microchimerism is a reliable indicator of incipient AML
      relapse.
AB  - INTRODUCTION: The reoccurrence or increase in autologous hematopoiesis after
      allogeneic transplantation has been linked to incipient leukemia relapse.
      However, the importance of such an emergency regarding microchimerism (i.e. mixed
      chimerism below 1% of autologous cells) still remains controversial, as
      fluctuating microchimerism can be observed for a very long time after
      transplantation. METHODS: Using real-time PCR (RQ-PCR), we compare peripheral
      blood samples obtained from patients with acute myeloid leukemia (AML) before
      hematological relapse and those taken during complete remission (i.e. either
      complete cytogenetic remission or complete molecular remission where applicable).
      By comparison of these two groups, we describe microchimerism dynamics clearly
      connected with imminent AML relapse. Additionally, we compare applicability of RQ
      PCR and conventional PCR with fragment analysis. RESULTS: Mere reappearance of
      autologous hematopoiesis within patients with complete donor chimerism is
      alarming, and another sample with further increase confirms ongoing relapse. In
      case of patients with continuous microchimerism, another two consecutive samples
      with increasing trend are required. RQ-PCR predicted a significantly higher
      number of hematological relapses (87%vs. 39%) with a median anticipation period
      of 33 days, 26 days earlier than conventional PCR (P= 0.0002). Moreover, the
      outcome of microchimerism dynamics was in complete agreement with monitoring of
      minimal residual disease when analyzed from the same cell compartment.
      CONCLUSION: Within this paper, we emphasize the importance of microchimerism
      monitoring as a reliable indicator of incipient AML relapse, especially in
      patients where no other specific molecular marker is available.

PMID- 20682000
TI  - Hematopoietic stem cell lodgment in the adult bone marrow stem cell niche.
AB  - Treatment of malignant blood disorders, such as leukemia, that can provide a
      better chance of long-term remission involves myeloablation followed by
      transplantation of matched donor hematopoietic stem cells (HSCs). For successful
      engraftment and re-establishment of hematopoiesis to occur in the recipient, the
      transplanted HSCs must first migrate from the blood circulation to the bone
      marrow (BM), a process known as homing, then localize and anchor in suitable
      microenvironments within the BM, a process known as lodgment. After lodgment, the
      specific fate of the transplanted HSCs is determined through complex,
      bidirectional interactions with various stromal cell components in the niche.
      Ultimately, these interactions dictate the clinical outcome of the
      transplantation. Through the use of transgenic mouse models, considerable
      evidence has been accumulated in an attempt to unveil the possible underlying
      mechanisms that govern these processes. Here, we will emphasize the major factors
      that are involved in the regulation of lodgment of transplanted HSCs.
      Specifically, we will first introduce early observations on the spatial
      distribution of hematopoietic progenitors within the BM, then we will discuss the
      soluble factors, chemokines, cell-cell interactions, and cell-matrix interactions
      that have been studied and known to influence the site of HSC lodgment within the
      BM following transplantation.

PMID- 20682001
TI  - CD95 is not functional in human erythrocytes.
AB  - INTRODUCTION: The CD95 pathway is a potent inducer of apoptosis in nucleated
      cells and this death receptor is important for proper blood cell development.
      Although it is expressed in red blood cells, its functional role in erythrocytes
      is not well documented. These anucleated cells can undergo cell death via
      eryptosis, a process showing similarities to apoptosis of nucleated cells. This
      mode of cell death is mainly triggered by oxidative stress or energy depletion.
      METHODS: CH11 was added to the purified human erythrocytes for induction of
      phosphatidylserine (PS) exposure. AnnexinV-FITC was used as a probe for PS
      detection. RESULTS: No significantly enhanced PS-positive cell fraction could be
      observed after erythrocytes were treated with CH11. CONCLUSION: Based on some key
      features for an activated CD95 system, this death receptor has been considered to
      induce PS exposure. However, we give evidence, that CD95 is not functional in red
      blood cells and that activation of this death receptor does not lead to the
      exposure of phosphatidylserine.

PMID- 20682003
TI  - Molecular diagnosis in allergy.
AB  - Development and progress made in the field of recombinant allergens have allowed
      for the development of a new concept in allergy diagnosis, molecular diagnosis
      (MD), which makes it possible to identify potential disease-eliciting molecules.
      Microarray-based testing performed with a small amount of serum sample enables
      clinicians to determine specific-IgE antibodies against multiple recombinants or
      purified natural allergen components. Performance characteristics of allergens so
      far tested are comparable with current diagnostic tests, but have to be confirmed
      in larger studies. The use of allergen components and the successful
      interpretation of test results in the clinic require some degree of knowledge
      about the basis of allergen components and their clinical implications. Allergen
      components can be classified by protein families based on their function and
      structure. This review provides a brief overview of basic information on allergen
      components, recombinants or purified, currently available or soon to become
      commercially available in ImmunoCAP or ISAC systems, including names, protein
      family and function. Special consideration is given to primary or species
      specific sensitization and possible cross-reactivity, because one of the most
      important clinical utility of MD is its ability to reveal whether the
      sensitization is genuine in nature (primary, species-specific) or if it is due to
      cross-reactivity to proteins with similar protein structures, which may help to
      evaluate the risk of reaction on exposure to different allergen sources. MD can
      be a support tool for choosing the right treatment for the right patient with the
      right timing. Such information will eventually give clinicians the possibility to
      individualize the actions taken, including an advice on targeted allergen
      exposure reduction, selection of suitable allergens for specific immunotherapy,
      or the need to perform food challenges. Nevertheless, all in vitro tests should
      be evaluated together with the clinical history, because allergen sensitization
      does not necessarily imply clinical responsiveness.

PMID- 20682004
TI  - How do teenagers manage their food allergies?
AB  - BACKGROUND: The peak incidence of deaths from anaphylaxis associated with nut
      allergy occurs in teenagers and young adults. During adolescence, the management
      of food allergy shifts from being the responsibility of parents to that of the
      young person. This is a group who therefore need special attention in the clinic.
      OBJECTIVE: This study aimed to understand the practical challenges that teenagers
      with food allergy experience using a qualitative approach and generate potential
      interventions for tackling these. METHODS: Teenagers aged 1118 years with food
      allergy completed a questionnaire about their food allergy and underwent a
      focused, semi-structured interview with open questions guided by a priori topic
      areas. Interviews were recorded, transcribed and analysed using a thematic
      approach. RESULTS: The study enrolled 18 teenagers with a median age of 15 years
      (10 females); the most common food allergens were peanuts and tree nuts. Three
      key themes emerged: avoidance of allergens, preparation for reactions and the
      treatment of reactions. The majority of teenagers reported eating foods labelled
      as 'may contain' an allergen as they perceive that they are actually very
      unlikely to contain an allergen. Many of the teenagers only carried their self
      injectable adrenaline when they thought they are particularly at risk of a
      reaction. Some do not know how to appropriately treat an allergic reaction. More
      than half believed that educating other students at school about the seriousness
      of food allergies would make it easier to live with their food allergy.
      CONCLUSIONS: A significant number of teenagers demonstrate risk-taking behaviour
      in the management of their food allergies. Teenagers also felt it would be
      helpful for their peers to be educated about food allergy. This novel strategy
      might help them to avoid trigger foods and enable teenagers to access help more
      readily if they suffer a reaction.

PMID- 20682002
TI  - T cells in multiple sclerosis and experimental autoimmune encephalomyelitis.
AB  - Multiple sclerosis (MS) is a demyelinating inflammatory disorder of the central
      nervous system (CNS), which involves autoimmune responses to myelin antigens.
      Studies in experimental autoimmune encephalomyelitis (EAE), an animal model for
      MS, have provided convincing evidence that T cells specific for self-antigens
      mediate pathology in these diseases. Until recently, T helper type 1 (Th1) cells
      were thought to be the main effector T cells responsible for the autoimmune
      inflammation. However more recent studies have highlighted an important
      pathogenic role for CD4(+) T cells that secrete interleukin (IL)-17, termed Th17,
      but also IL-17-secreting gammadelta T cells in EAE as well as other autoimmune
      and chronic inflammatory conditions. This has prompted intensive study of the
      induction, function and regulation of IL-17-producing T cells in MS and EAE. In
      this paper, we review the contribution of Th1, Th17, gammadelta, CD8(+) and
      regulatory T cells as well as the possible development of new therapeutic
      approaches for MS based on manipulating these T cell subtypes.

PMID- 20682005
TI  - Immunolocalization of estrogen-producing and metabolizing enzymes in benign
      breast disease: comparison with normal breast and breast carcinoma.
AB  - It is well known that estrogens play important roles in the cell proliferation of
      breast carcinoma. Benign breast disease (BBD) contains a wide spectrum of
      diseases, and some are considered an important risk factor for subsequent breast
      carcinoma development. However, the significance of estrogens in BBD has remained
      largely unknown. Therefore, in this study, we examined tissue concentrations of
      estrogens and immunolocalization of estrogen-producing/metabolizing enzymes in
      BBD, and compared these findings with those in the normal breast and ductal
      carcinoma in situ (DCIS). Tissue concentration of estradiol in BBD (n = 9) was
      significantly (3.4-fold) higher than normal breast (n = 9) and nearly the same
      (0.7-fold) as in DCIS (n = 9). Immunoreactivity of estrogen sulfotransferase in
      BBD was significantly lower (n = 82) than normal breast (n = 28) but was not
      significantly different from DCIS (n = 28). Aromatase and steroid sulfatase
      immunoreactivities tended to be higher (P = 0.07) in BBD than in normal breast,
      and 17beta-hydroxysteroid dehydrogenase type 1 immunoreactivity was significantly
      higher in BBD than normal breast in the postmenopausal tissues. Immunoreactivity
      of estrogen and progesterone receptors was also significantly higher in BBD than
      normal breast. These results suggest that tissue concentration of estradiol is
      increased in BBD at a level similar to DCIS, which is considered mainly due to
      loss of estrogen sulfotransferase expression. Increased local estradiol
      concentration in BBD due to aberrant expression of estrogen
      producing/metabolizing enzymes may play important roles in the accumulation of
      estradiol-mediated growth and/or subsequent development of breast carcinoma.

PMID- 20682006
TI  - Novel classification based on immunohistochemistry combined with hierarchical
      clustering analysis in non-functioning neuroendocrine tumor patients.
AB  - Somatostatin analogues ameliorated many symptoms caused by neuroendocrine tumors
      (NET), but their antitumor activities are limited especially in non-functioning
      cases. An overactivation of signaling pathways under receptor tyrosine-kinase
      (RTK) has been recently demonstrated in some NET patients, but its details have
      remained largely unknown. Therefore, in this study, we immunolocalized
      therapeutic factors and evaluated the data to study the clinical significance of
      the molecules in non-functioning Japanese gastrointestinal NET. Fifty-two NET
      cases were available for examination in this study and expression of somatostatin
      receptor (sstr) 1, 2A, 2B, 3 and 5, activated form of mammalian target of
      rapamycin (mTOR), eukaryotic initiation factor 4-binding protein 1 (4EBP1),
      ribosomal protein s6 (S6), extracellular signal-regulated kinase (ERK) and
      insulin-like growth factor 1 receptor (IGF-1R) was evaluated using
      immunohistochemistry. We then studied the correlation among the
      immunohistochemical results of the individual cases using hierarchical clustering
      analysis. Results of clustering analysis demonstrated that NET cases were
      basically classified into Cluster I and II. Cluster I was associated with higher
      expression of sstr1, 2B and 3 and Cluster II was characterized by an activation
      of the PI3K/Akt pathway and IGF-1R and higher proliferative status. Cluster II
      was further classified into Cluster IIa and IIb. Cluster IIa was associated with
      higher expression of sstr1 and 5 and higher proliferative status and Cluster IIb
      was characterized by ERK activation. Hierarchical clustering analysis of
      immunoreactivity of the therapeutic factors can classify NET cases into three
      distinctive groups and the medical treatment may be determined according to this
      novel classification method for non-functioning NET patients.

PMID- 20682007
TI  - How zooplankton feed: mechanisms, traits and trade-offs.
AB  - Zooplankton is a morphologically and taxonomically diverse group and includes
      organisms that vary in size by many orders of magnitude, but they are all faced
      with the common problem of collecting food from a very dilute suspension. In
      order to maintain a viable population in the face of mortality, zooplankton in
      the ocean have to clear daily a volume of ambient water for prey particles that
      is equivalent to about 10(6) times their own body volume. While most size
      specific vital rates and mortality rates decline with size, the clearance
      requirement is largely size-independent because food availability also declines
      with size. There is a limited number of solutions to the problem of concentrating
      dilute prey from a sticky medium: passive and active ambush feeding; feeding
      current feeding, where the prey is either intercepted directly, retained on a
      filter, or individually perceived and extracted from the feeding current; cruise
      feeding; and colonization of large particles and marine snow aggregates. The
      basic mechanics of these food-collection mechanisms are described, and it is
      shown that their efficiencies are inherently different and that each of these
      mechanisms becomes less efficient with increasing size. Mechanisms that
      compensate for this decline in efficiency are described, including inflation of
      feeding structures and development of vision. Each feeding mode has implications
      beyond feeding in terms of risk of encountering predators and chance of meeting
      mates, and they partly target different types of prey. The main dichotomy is
      between (inefficient) ambush feeding on motile prey and the more efficient active
      feeding modes; a secondary dichotomy is between (efficient) hovering and (less
      efficient) cruising feeding modes. The efficiencies of the various feeding modes
      are traded off against feeding-mode-dependent metabolic expenses, predation
      risks, and mating chances. The optimality of feeding strategies, evaluated as the
      ratio of gain over risk, varies with the environment, and may explain both size
      dependent and spatio-temporal differences in distributions of various feeding
      types as well as other aspects of the biology of zooplankton (mating behaviour,
      predator defence strategies).

PMID- 20682008
TI  - Percentiles and mean values for neck circumference in Turkish children aged 6-18
      years.
AB  - AIM: To provide neck circumference (NC) percentiles and mean values for Turkish
      children and to investigate their significance in clinical and epidemiological
      use. METHODS: Data were obtained from a cross-sectional screening study; DAMTCA
      II (Determination of Anthropometric Measurements in Turkish Children and
      Adolescents) in which 5481 subjects from 17 primary, secondary and high schools
      were included. NC percentiles were produced using the LMS method, and NC was
      compared with other parameters which define body fat distribution. RESULTS: The
      smoothed NC curves of 3rd, 5th, 15th, 25th, 50th, 75th, 85th, 90th, 95th and 97th
      percentiles were constructed by age and gender. The descriptive characteristics
      of collected data were presented as mean (SD: standard deviation) and median (Min
      Max: minimum-maximum) to provide detailed information other than smoothed values.
      The most prominent finding of this study was that the NC of boys was greater, but
      not significantly higher, than that of girls until the age of 12 but later a
      prominent increase in the NC of boys is observed compared with girls. We compared
      obese and non-obese children in the 6-10, 11-13, 14-18 age groups, NC was found
      to be an important parameter to define obesity. CONCLUSIONS: This study provides
      NC percentiles, means and medians values and analyses their significance in
      obesity evaluation in clinical practice.

PMID- 20682009
TI  - Histological study of the parotid and mandibular glands of barking deer
      (Muntiacus muntjak) with special reference to the distribution of carbohydrate
      content.
AB  - We investigated the histology and carbohydrate content of the parotid and
      mandibular glands of the barking deer (Muntiacus muntjak). Three adult males were
      used. Paraffin wax sections of the glands were stained with haematoxylin and
      eosin (HE), alcian blue (AB), pH 2.5 and periodic acid Schiff (PAS). The acinar
      cells of the parotid gland were serous, whereas those of the mandibular gland
      were of the mixed type. The acini of the mandibular gland comprised serous and
      mucous cells with the mucous type predominating. AB and PAS staining showed high
      concentrations of acidic and neutral carbohydrates in the mucous cells, but not
      in the serous cells of the mandibular gland. These carbohydrates were also found
      in moderate-to-high concentrations in the secreted material in the mandibular
      duct lumen. However, these carbohydrates were not found in acinar cells of the
      parotid gland or in the serous cells of the mandibular gland. Thus, carbohydrates
      in the saliva of the barking deer appear to be produced mainly by the mucous
      cells of the mandibular glands.

PMID- 20682010
TI  - Proximity to the US-Mexico border: a key to explaining geographic variation in US
      methamphetamine, cocaine and heroin purity.
AB  - AIMS: Although illicit drug purity is a widely discussed health risk, research
      explaining its geographic variation within a country is rare. This study examines
      whether proximity to the US-Mexico border, the United States' primary drug import
      portal, is associated with geographic variation in US methamphetamine, heroin and
      cocaine purity. DESIGN: Distances (proximity) between the US-Mexico border and
      locations of methamphetamine, cocaine and heroin seizures/acquisitions (n =
      239,070) recorded in STRIDE (System to Retrieve Information from Drug Evidence)
      were calculated for the period of 1990-2004. The association of drug purity with
      these distances and other variables, including time and seizure/acquisition size,
      was examined using hierarchical multivariate linear modeling (HMLM). SETTING:
      Coterminous United States. FINDINGS: Methamphetamine, cocaine and heroin purity
      generally decreased with distance from the US-Mexico border. Heroin purity,
      however, after initially declining with distance, turned upwards-a U-shaped
      association. During 2000-04, methamphetamine purity also had a U-shaped
      association with distance. For each of the three drugs, temporal changes in the
      purity of small acquisitions (<10 g) were typically more dynamic in areas closer
      to the US-Mexico border. CONCLUSIONS: Geographic variance in methamphetamine,
      cocaine and heroin purity throughout the coterminous United States was associated
      with US-Mexico border proximity. The U-shaped associations between border
      distance and purity for heroin and methamphetamine may be due to imports of those
      drugs via the eastern United States and southeast Canada, respectively. That
      said, areas closer to the US-Mexico border generally had relatively high illicit
      drug purity, as well as more dynamic change in the purity of small ('retail
      level') drug amounts.

PMID- 20682012
TI  - Oral maribavir for treatment of refractory or resistant cytomegalovirus
      infections in transplant recipients.
AB  - BACKGROUND: Despite advances in cytomegalovirus (CMV) prophylaxis and therapy,
      some transplant recipients still develop refractory CMV infections. Maribavir
      (MBV), an investigational benzimidazole antiviral agent, acts by a mechanism
      different from that of existing anti-CMV drugs. Previous Phase I and II studies
      have demonstrated a favorable safety profile for MBV, but its utility in
      treatment of complex CMV syndromes is unknown. METHODS: Between June and December
      2008, MBV was released for use under individual emergency investigational new
      drug applications requested by treating physicians and approved by the US Food
      and Drug Administration and local institutional review boards. Six patients (5
      solid organ transplant recipients and 1 hematopoietic stem cell transplant
      recipient) who had failed to respond to other therapies and/or had known
      ganciclovir-resistant CMV were treated with MBV at a starting oral dose of 400 mg
      twice daily. RESULTS: Patients were treated for a median of 207 days (range, 15
      376). Four of 6 patients had no detectable CMV DNAemia within 6 weeks of starting
      MBV therapy. One patient, who had an initial viral load of 1.8 million copies/mL,
      developed MBV resistance mutations. One patient, who had low serum levels of MBV,
      had persistent CMV DNAemia and viruria without developing genotypic or phenotypic
      resistance to MBV. One patient cleared CMV DNAemia, but died of pneumonia and
      multiorgan failure. No significant adverse effects attributable to MBV were
      observed. CONCLUSIONS: MBV deserves further systematic evaluation as treatment
      for CMV infection that is resistant and/or refractory to standard therapies, but
      its optimal dose, duration of therapy, and use in combinations versus as a single
      agent have yet to be determined.

PMID- 20682013
TI  - Td92, an outer membrane protein of Treponema denticola, induces
      osteoclastogenesis via prostaglandin E(2)-mediated RANKL/osteoprotegerin
      regulation.
AB  - BACKGROUND AND OBJECTIVE: Periodontitis is a chronic inflammatory disease of the
      periodontium that causes significant alveolar bone loss. Osteoclasts are bone
      resorbing multinucleated cells. Osteoblasts regulate osteoclast differentiation
      by expression of RANKL and osteoprotegerin (OPG). Td92 is a surface-exposed outer
      membrane protein of Treponema denticola, a periodontopathogen. Although it has
      been demonstrated that Td92 acts as a stimulator of various proinflammatory
      mediators, the role of Td92 in alveolar bone resorption remains unclear.
      Therefore, in this study, we investigated the role of Td92 in bone resorption.
      MATERIAL AND METHODS: Mouse bone marrow cells were co-cultured with calvariae
      derived osteoblasts in the presence or absence of Td92. Osteoclast formation was
      assessed by TRAP staining. Expressions of RANKL, osteoprotegerin (OPG) and
      prostaglandin E(2) (PGE(2) ) in osteoblasts were estimated by ELISA. RESULTS:
      Td92 induced osteoclast formation in the co-cultures. In the osteoblasts, RANKL
      and PGE(2) expressions were up-regulated, whereas OPG expression was down
      regulated by Td92. The addition of OPG inhibited Td92-induced osteoclast
      formation. The prostaglandin synthesis inhibitors NS398 and indomethacin were
      also shown to inhibit Td92-induced osteoclast formation. The effects of Td92 on
      the expressions of RANKL, OPG and PGE(2) in osteoblasts were blocked by NS398 or
      indomethacin. CONCLUSION: These results suggest that Td92 promotes osteoclast
      formation through the regulation of RANKL and OPG production via a PGE(2) 
      dependent mechanism.

PMID- 20682011
TI  - 1H and 31P NMR lipidome of ethanol-induced fatty liver.
AB  - BACKGROUND:  Hepatic steatosis (fatty liver), an early and reversible stage of
      alcoholic liver disease, is characterized by triglyceride deposition in
      hepatocytes, which can advance to steatohepatitis, fibrosis, cirrhosis, and
      ultimately to hepatocellular carcinoma. In the present work, we studied altered
      plasma and hepatic lipid metabolome (lipidome) to understand the mechanisms and
      lipid pattern of early-stage alcohol-induced-fatty liver. METHODS:  Male Fischer
      344 rats were fed 5% alcohol in a Lieber-DeCarli diet. Control rats were pair-fed
      an equivalent amount of maltose-dextrin. After 1 month, animals were killed and
      plasma collected. Livers were excised for morphological, immunohistochemical, and
      biochemical studies. The lipids from plasma and livers were extracted with methyl
      tert-butyl ether and analyzed by 750/800 MHz proton nuclear magnetic resonance
      (1H NMR) and phosphorus (31P) NMR spectroscopy on a 600 MHz spectrometer. The NMR
      data were then subjected to multivariate statistical analysis. RESULTS: 
      Hematoxylin and Eosin and Oil Red O stained liver sections showed significant
      fatty infiltration. Immunohistochemical analysis of liver sections from ethanol
      fed rats showed no inflammation (absence of CD3 positive cells) or oxidative
      stress (absence of malondialdehyde reactivity or 4-hydroxynonenal positive
      staining). Cluster analysis and principal component analysis of 1H NMR data of
      lipid extracts of both plasma and livers showed a significant difference in the
      lipid metabolome of ethanol-fed versus control rats. 31P NMR data of liver lipid
      extracts showed significant changes in phospholipids similar to 1H NMR data. 1H
      NMR data of plasma and liver reflected several changes, while comparison of 1H
      NMR and 31P NMR data offered a correlation among the phospholipids. CONCLUSIONS: 
      Our results show that alcohol consumption alters metabolism of cholesterol,
      triglycerides, and phospholipids that could contribute to the development of
      fatty liver. These studies also indicate that fatty liver precedes oxidative
      stress and inflammation. The similarities observed in plasma and liver lipid
      profiles offer a potential methodology for detecting early-stage alcohol-induced
      fatty liver disease by analyzing the plasma lipid profile.

PMID- 20682014
TI  - Aging affects the phenotypic characteristics of human periodontal ligament cells
      and the cellular response to hormonal stimulation in vitro.
AB  - BACKGROUND AND OBJECTIVE: Aging modulates the proliferative activity and organic
      matrix production of cells in vivo and in vitro. Here, we explore how aging
      affects the phenotypic characteristics of human periodontal ligament cells and
      their response to hormonal stimulation. MATERIAL AND METHODS: Fifth passage
      periodontal ligament cells from subjects aged 12-14 (group 1), 41-55 (group 2)
      and 61-70 years (group 3) were characterized for the expression of mesenchymal
      marker genes and proteins by real-time PCR and flow cytometry. Confluent cultures
      were exposed to 10(-12) m parathyroid hormone(1-34) [PTH(1-34)] intermittently
      for three cycles. At harvest, cell number, alkaline phosphatase activity and
      osteocalcin production were determined by cell count, biochemical assay and
      ELISA. RESULTS: The characterization of the cells revealed a decreased expression
      of osteoblast-specific marker genes along with a lower percentage of cells
      presenting the respective proteins with age. An intermittent exposure of the
      cultures to 10(-12) m PTH(1-34) induced an increase of the cell number as opposed
      to a significant decrease of alkaline phosphatase activity and osteocalcin
      production. The cellular response to PTH(1-34) was strongest in group 1. Basal
      osteoprotegerin levels were highest in the cultures from the oldest donors and
      inhibited by intermittent PTH(1-34) in all groups. CONCLUSION: Our data indicate
      that periodontal ligament cells from older subjects display a less differentiated
      phenotype and a reduced response to intermittent PTH, suggesting a compromised
      ability to maintain tissue homeostasis and a limited possibility to support
      periodontal repair processes with age. The high basal osteoprotegerin expression
      in older subjects might serve as a compensatory mechanism.

PMID- 20682015
TI  - 18beta-glycyrrhetinic acid inhibits periodontitis via glucocorticoid-independent
      nuclear factor-kappaB inactivation in interleukin-10-deficient mice.
AB  - BACKGROUND AND OBJECTIVE: 18beta-Glycyrrhetinic acid (GA) is a natural anti
      inflammatory compound derived from licorice root extract (Glycyrrhiza glabra).
      The effect of GA on experimental periodontitis and its mechanism of action were
      determined in the present study. MATERIAL AND METHODS: Periodontitis was induced
      by oral infection with Porphyromonas gingivalis W83 in interleukin-10-deficient
      mice. The effect of GA, which was delivered by subcutaneous injections in either
      prophylactic or therapeutic regimens, on alveolar bone loss and gingival gene
      expressions was determined on day 42 after initial infection. The effect of GA on
      lipopolysaccharide (LPS)-stimulated macrophages, T cell proliferation and
      osteoclastogenesis was also examined in vitro. RESULTS: 18beta-Glycyrrhetinic
      acid administered either prophylactically or therapeutically resulted in a
      dramatic reduction of infection-induced bone loss in interleukin-10-deficient
      mice, which are highly disease susceptible. Although GA has been reported to
      exert its anti-inflammatory activity via downregulation of 11beta-hydroxysteroid
      dehydrogenase-2 (HSD2), which converts active glucocorticoids to their inactive
      forms, GA did not reduce HSD2 gene expression in gingival tissue. Rather, in
      glucocorticoid-free conditions, GA potently inhibited LPS-stimulated
      proinflammatory cytokine production and RANKL-stimulated osteoclastogenesis, both
      of which are dependent on nuclear factor-kappaB. Furthermore, GA suppressed LPS-
      and RANKL-stimulated phosphorylation of nuclear factor-kappaB p105 in vitro.
      CONCLUSION: These findings indicate that GA inhibits periodontitis by
      inactivation of nuclear factor-kappaB in an interleukin-10- and glucocorticoid
      independent fashion.

PMID- 20682016
TI  - Type 1 diabetes predisposes to enhanced gingival leukocyte margination and
      macromolecule extravasation in vivo.
AB  - BACKGROUND AND OBJECTIVE: Diabetes predisposes to periodontal disease. However,
      the cellular and molecular mechanisms linking the two conditions are not clear.
      The impact of chronic hyperglycemia on leukocyte margination and macromolecule
      extravasation was determined in gingival vessels in vivo. MATERIALS AND METHODS:
      Gingival intravital microscopy was employed to measure extravasation of
      fluorescein isothiocyanate (FITC)-dextran in diabetic Akita and healthy wild-type
      (WT) mice. Rhodamine 6G and FITC-LY6G were injected for nonspecific and
      polymorphonuclear-specific leukocyte labeling, respectively. Surface expression
      of leukocyte adhesion molecules was determined with flow cytometry and western
      blotting. RESULTS: Vascular permeability was significantly increased in Akita
      gingival vessels compared with WT [permeability index (PI): WT, 0.75 +/- 0.05;
      Akita, 1.1 +/- 0.03: p < 0.05). Wild-type gingival vessels reached comparable
      permeability 2 h after intragingival injection of tumor necrosis factor alpha
      (TNFalpha), used here as positive control (PI, 1.17 +/- 0.16). The number of
      rolling leukocytes was significantly elevated in diabetic gingiva (WT, 25 +/- 3.7
      cells/min; Akita, 42 +/- 8.5 cells/min; p < 0.03). Similar rolling cell counts
      were obtained in WT after intragingival injection of TNFalpha (10 ng TNFalpha, 47
      +/- 1.3 cells/min; 100 ng TNFalpha, 57.5 +/- 5.85 cells/min). The number of
      leukocytes firmly attached to the endothelium was similar in WT and Akita mice.
      Leukocyte cell-surface expression of P-selectin glycoprotein ligand-1 and CD11a
      was increased in Akita mice, while L-selectin remained unchanged when compared
      with WT. Moreover, P-selectin expression in Akita gingival tissues was elevated
      compared with that of WT. CONCLUSION: Chronic hyperglycemia induces a
      proinflammatory state in the gingival microcirculation characterized by increased
      vascular permeability, and leukocyte and endothelial cell activation. Leukocyte
      induced microvascular damage, in turn, may contribute to periodontal tissue
      damage in diabetes.

PMID- 20682017
TI  - The effect of full-mouth tooth extraction on glycemic control among patients with
      type 2 diabetes requiring extraction of all remaining teeth: a randomized
      clinical trial.
AB  - BACKGROUND AND OBJECTIVE: Several studies have shown that periodontitis can
      complicate the severity of diabetes by worsening the degree of glycemic control.
      The purpose of this study was to determine the effect of full-mouth tooth
      extraction on glycemic control among type 2 diabetic patients. MATERIAL AND
      METHODS: A total of 58 patients with type 2 diabetes mellitus and advanced
      periodontitis who were requiring extraction of all remaining teeth were
      randomized consecutively into treatment (full-mouth tooth extraction) and control
      groups (no treatment). Eight patients were lost to follow-up or reported use of
      antibiotics, leaving 50 patients to be included in the analysis. All patients had
      all their remaining teeth in a hopeless condition. Relevant data were collected,
      and glycosylated hemoglobin (HbA(1c) ) and fasting blood glucose levels were
      measured at baseline and at follow-up times of 3 and 6 mo. RESULTS: At baseline,
      the mean (SD) HbA(1c) level was 8.6% (1.24) in the treatment group and 7.7%
      (0.87) in the control group. In the treatment group, the mean HbA(1c) level
      decreased significantly from 8.6% at baseline to 7.4% after 3 mo of denture
      treatment, and continued to decrease to 7.3% after 6 mo. In the control group,
      the mean HbA(1c) decreased from 7.7% at baseline to 7.5% after 3 mo, and remained
      almost the same after 6 mo. After adjusting for the baseline HbA(1c) , the mean
      reduction in HbA(1c) after 3 mo in the treatment group [1.23% (0.79)] was
      significantly higher than the mean reduction in the control group [0.28% (0.87)].
      CONCLUSION: Full-mouth tooth extraction resulted in an improvement in glycemic
      control among diabetic patients. Large-scale multicentre clinical trials are
      needed to confirm the current evidence.

PMID- 20682018
TI  - Differential effects of prostaglandin E(2) and enamel matrix derivative on the
      proliferation of human gingival and dermal fibroblasts and gingival
      keratinocytes.
AB  - BACKGROUND AND OBJECTIVE: Elevated levels of prostaglandins contribute to
      periodontal destruction but can impair gingival healing by affecting local
      fibroblasts. Enamel matrix derivative (EMD) has beneficial effects on supporting
      and gingival tissues. We showed that prostaglandin E(2) (PGE(2) ) inhibits the
      proliferation of human gingival fibroblasts (hGFs) and that EMD stimulates it.
      Prostaglandins and EMD may also affect skin healing by targeting dermal
      fibroblasts (DFs). Thus, we compared the effects of these two agents on the
      proliferation of hGFs, human gingival keratinocytes (hGKs) and hDFs. MATERIAL AND
      METHODS: Cells from healthy human gingiva or skin were treated with PGE(2) and/or
      EMD, and proliferation was assessed by measuring cell number and DNA synthesis.
      RESULTS: In hGFs, PGE(2) (1 MUm) inhibited proliferation while EMD stimulated it.
      When present together, EMD abolished the PGE(2) -induced inhibition. Serum
      increased (by a factor of 10) the amount of phosphorylated extracellular signal
      regulated kinase (p-ERK), PGE(2) reduced it (by 70-80%) and EMD restored it when
      present with PGE(2). Prostaglandin E(2) stimulated cAMP production in hGFs while
      serum or EMD did not. Enamel matrix derivative stimulated hDF proliferation, but
      the inhibitory effect of PGE(2) was milder than with hGFs. When present together,
      EMD abolished the PGE(2) -induced inhibition. Enamel matrix derivative inhibited
      the proliferation of primary hGKs, but PGE(2) had no effect. Finally, we found
      that hDFs contained about five times less prostaglandin EP(2) receptor mRNA than
      hGFs, while hGKs contained none. CONCLUSION: Prostaglandin E(2) inhibits and EMD
      stimulates hGF proliferation via distinct pathways. The different sensitivities
      of hDFs and hGKs to PGE(2) can be explained by the levels of EP(2) expression.

PMID- 20682019
TI  - Expression of periodontal interleukin-6 protein is increased across patients with
      neither periodontal disease nor diabetes, patients with periodontal disease alone
      and patients with both diseases.
AB  - BACKGROUND AND OBJECTIVE: Epidemiological studies have established that patients
      with diabetes have an increased prevalence and severity of periodontal disease.
      Interleukin (IL)-6, a multifunctional cytokine, plays a role in the tissue
      inflammation that characterizes periodontal disease. Our recent study has shown a
      trend of increase in periodontal IL-6 expression at the mRNA level across
      patients with neither periodontal disease nor diabetes, patients with periodontal
      disease alone and patients with both diseases. However, the periodontal IL-6
      expression at the protein level in these patients has not been investigated.
      MATERIAL AND METHODS: Periodontal tissue specimens were collected from eight
      patients without periodontal disease and diabetes (group 1), from 17 patients
      with periodontal disease alone (group 2) and from 10 patients with both
      periodontal disease and diabetes (group 3). The frozen sections were prepared
      from these tissue specimens and IL-6 protein expression was detected and
      quantified. RESULTS: The nonparametric Kruskal-Wallis test showed that the
      difference in IL-6 protein levels among the three groups was statistically
      significant (p = 0.035). Nonparametric analysis using the Jonckheere-Terpstra
      test showed a tendency of increase in periodontal IL-6 protein levels across
      group 1 to group 2 to group 3 (p = 0.006). Parametric analysis of variance
      (ANOVA) on IL-6 protein levels showed that neither age nor gender significantly
      affected the difference of IL-6 levels among the groups. CONCLUSION: Periodontal
      IL-6 expression at the protein level is increased across patients with neither
      periodontal disease nor diabetes, patients with periodontal disease alone and
      patients with both diseases.

PMID- 20682020
TI  - A prospective randomized study comparing cyclosporine versus tacrolimus combined
      with daclizumab, mycophenolate mofetil, and steroids in heart transplantation.
AB  - BACKGROUND: Cyclosporine (CsA) and tacrolimus (Tac) in heart transplantation
      (HTx) have been compared but with certain drawbacks. We compared both drugs in a
      prospective analysis with medium-term follow-up. METHODS: Hundred and six
      patients were randomized to receive CsA or Tac (53 per group). Target levels of
      CsA were 200-300 ng/mL in the first six months and 100-200 ng/mL thereafter. Tac
      levels were 10-15 and 5-10 ng/mL, respectively. We also used daclizumab as
      induction and mycophenolate mofetil (MMF) and steroids as maintenance therapy.
      RESULTS: Baseline characteristics were similar. Survival (CsA 88.7% vs. Tac
      81.1%; p = 0.493) was similar. There was a tendency for longer time to first
      rejection with CsA (93 +/- 110 vs. 55 +/- 81 d; p = 0.122). There were more
      rejection-free patients with Tac (39 vs. 28%; p = 0.233). CsA patients suffered
      more viral infections (0.41 +/- 0.58 vs. 0.11 +/- 0.31; p = 0.003). CsA patients
      developed hypertension often (64 vs. 43%; p = 0.032). Tac patients suffered more
      gastrointestinal complications (16 vs. 6%; p = 0.042). Renal function and the
      development of diabetes, dyslipidemia, or neurological complications was similar.
      CONCLUSIONS: Tac patients showed a tendency for longer time to first rejection,
      and there were more rejection-free patients with Tac and suffered fewer viral
      infections. Tac patients developed less hypertension and needed less drugs for
      its control. Renal function was similar in both groups.

PMID- 20682021
TI  - The effect of HLA mismatch on highly sensitized renal allograft recipients.
AB  - INTRODUCTION: We examined the effects of increasing human leukocyte antigen (HLA)
      mismatches (MM) on long-term graft outcomes in patients transplanted with a panel
      reactive antibody (PRA) >80% over a 10-yr period. METHODS: A total of 142
      recipients were divided into three groups based on the number of HLA MM with
      their allograft (0-2, 3-4 and 5-6 MM; Groups I, II and III). All patients
      received the same immunosuppression protocol. RESULTS: The higher MM groups had a
      higher incidence of rejection (4.4% vs. 11.4% vs. 31.3%, p < 0.01). A
      multivariate analysis showed that rejection was the only significant variable
      affecting graft loss (OR = 7.45, p = 0.01). There was a trend toward more CMV
      infection and worse graft function with higher MM. Kaplan-Meier five-yr graft
      survival estimates were 100% vs. 81% vs. 74% for Groups I, II and III,
      respectively (p = 0.14). CONCLUSIONS: In patients with PRA levels >80%, a higher
      HLA MM is associated with higher incidence of acute rejection. Acute rejection
      was the only significant variable affecting graft loss. We found a trend toward
      more CMV infections and worse graft outcomes with higher MM. Closer HLA matching
      and immunologic monitoring needs to be considered to improve graft outcomes among
      sensitized recipients.

PMID- 20682022
TI  - Perinatal complications increase the risk of postpartum depression. The
      Generation R Study.
AB  - OBJECTIVE:   To examine whether specific pregnancy and delivery complications are
      risk factors for postpartum depression. DESIGN:   A prospective longitudinal
      study. SETTING:  Rotterdam, the Netherlands. POPULATION:  A cohort of 4941
      pregnant women who enrolled in the Generation R Study. METHODS:   Information on
      perinatal complications was obtained from the midwife and hospital registries or
      by questionnaire. Logistic regression analyses were used to calculate the risk of
      postpartum depression for the separate perinatal complications. MAIN OUTCOME
      MEASURES: Postpartum psychiatric symptoms were assessed 2 months after delivery
      using the Edinburgh postnatal depression scale. RESULTS:  Several perinatal
      complications were significantly associated with postpartum depression, namely:
      pre-eclampsia (adjusted OR, aOR 2.58, 95% CI 1.30-5.14), hospitalization during
      pregnancy (aOR 2.25, 95% CI 1.19-4.26), emergency caesarean section (aOR 1.53,
      95% CI 1.02-2.31), suspicion of fetal distress (aOR 1.56, 95% CI 1.08-2.27), a
      medically indicated delivery provided by an obstetrician (aOR 2.43, 95% CI 1.56
      3.78), and hospital admission of the baby (aOR 1.45, 95% CI 1.10-1.92). Unplanned
      pregnancy, thrombosis, meconium-stained amniotic fluid, and Apgar score were not
      associated with postpartum depression after adjustment for confounding factors,
      such as pre-existing psychopathological symptoms and sociodemographic
      characteristics. The risk of postpartum depression increased with the number of
      perinatal complications women experienced (P < 0.001). CONCLUSIONS:  We showed
      that several pregnancy and delivery complications present a risk for women's
      mental health in the postpartum period. Obstetricians, midwives, general
      practitioners, and staff at baby well clinics should be aware that women who
      experienced perinatal complications-especially those with a number of perinatal
      complications-are at risk for developing postpartum depression.

PMID- 20682023
TI  - Prevention of gestational diabetes: design of a cluster-randomized controlled
      trial and one-year follow-up.
AB  - BACKGROUND: Annual prevalence of gestational diabetes mellitus (GDM) is 12.5%
      among Finnish pregnant women. The prevalence is expected to rise with the
      increasing overweight among women before pregnancy. Physical activity and diet
      are both known to have favourable effects on insulin resistance and possibly on
      the risk of GDM. We aimed to investigate, whether GDM can be prevented by
      counseling on diet, physical activity and gestational weight gain during
      pregnancy. METHODS/DESIGN: A cluster-randomized controlled trial was conducted in
      14 municipalities in the southern part of Finland. Pairwise randomization was
      performed in order to take into account socioeconomic differences. Recruited
      women were at 8-12 weeks' gestation and fulfilled at least one of the following
      criteria: body mass index>or=25 kg/m2, history of earlier gestational glucose
      intolerance or macrosomic newborn (>4500 g), age>or=40 years, first or second
      degree relative with history of type 1 or 2 diabetes. Main exclusion criterion
      was pathological oral glucose tolerance test (OGTT) at 8-12 weeks' gestation. The
      trial included one counseling session on physical activity at 8-12 weeks'
      gestation and one for diet at 16-18 weeks' gestation, and three to four booster
      sessions during other routine visits. In the control clinics women received usual
      care. Information on height, weight gain and other gestational factors was
      obtained from maternity cards. Physical activity, dietary intake and quality of
      life were followed by questionnaires during pregnancy and at 1-year postpartum.
      Blood samples for lipid status, hormones, insulin and OGTT were taken at 8-12 and
      26-28 weeks' gestation and 1 year postpartum. Workability and return to work were
      elicited by a questionnaire at 1- year postpartum. Linkage to the national birth
      register of years 2007-2009 will provide information on perinatal complications
      and GDM incidence among the non-participants of the study. Cost-effectiveness
      evaluation will be based on quality-adjusted life years. This study has received
      ethical approval from the Ethical board of Pirkanmaa Hospital District.
      DISCUSSION: The study will provide information on the effectiveness and cost
      effectiveness of gestational physical activity and dietary counseling on
      prevention of GDM in a risk group of women. Also information on the prevalence of
      GDM and postpartum metabolic syndrome will be gained. Results on maintaining the
      possible health behaviour changes are important in order to prevent chronic
      diseases such as cardiovascular disease and diabetes. TRIAL REGISTRATION: The
      trial is registered ISRCTN 33885819.

PMID- 20682024
TI  - The Tinnitus Research Initiative (TRI) database: a new approach for delineation
      of tinnitus subtypes and generation of predictors for treatment outcome.
AB  - Tinnitus, the phantom perception of sound, is a frequent disorder that causes
      significant morbidity and treatment is elusive. A large variety of different
      treatment options have been proposed and from most of them some patients benefit.
      However, a particular treatment that helps one patient may fail for others. This
      suggests that there are different forms of tinnitus which differ in their
      pathophysiology and their response to specific treatments. Therefore, it is a
      major challenge for tinnitus treatment to identify the most promising therapy for
      a specific patient. However, most published clinical treatment studies have
      enrolled only relatively small patient samples, making it difficult to identify
      predictors of treatment response for specific approaches. Furthermore, inter
      study comparability is limited because of varying methods of tinnitus assessment
      and different outcome parameters. Performing clinical trials according to
      standardized methodology and pooling the data in a database should facilitate
      both clinical subtypisation of different forms of tinnitus, and identification of
      promising treatments for different types of tinnitus. This would be an important
      step towards the goal of individualized treatment of tinnitus.For these reasons,
      an international database of tinnitus patients, who undergo specific treatments,
      and are assessed during the course of this treatment with standardized
      instruments (e.g., psychoacoustic measures, questionnaires) has been established.
      The primary objectives of this database are (1) collecting a standardized set of
      data on patient characteristics, treatments, and outcomes from tinnitus patients
      consulting specialized tinnitus clinics all over the world (at present 13 centers
      in 8 countries), (2) delineating different subtypes of tinnitus based on data
      that has been systematically collected and (3) identifying predictors for
      individual treatment response based on the clinical profile. Starting in 2008,
      the database currently contains data from more than 400 patients. It is expected
      that more centers will join the project and that the patient numbers will rapidly
      grow, so that this international database will further facilitate future research
      and contribute to the development of evidence based on individualized treatment.

PMID- 20682025
TI  - A new device to seal large coronary aneurysms: a case report.
AB  - INTRODUCTION: Coronary artery aneurysm is an uncommon disease. It is defined as a
      coronary artery dilatation, exceeding the diameter of the normal adjacent segment
      or the diameter of the patient's largest coronary vessel by 1.5 to 2 times.
      Coronary artery aneurysms are typically diagnosed by coronary angiography. The
      prognosis of coronary artery aneurysm is not well known and the management is
      challenging. CASE PRESENTATION: A 68-year-old Italian-Caucasian man presented to
      our hospital with angina. Coronary angiography revealed a large coronary aneurysm
      of the right coronary artery, which was successfully treated by the percutaneous
      implantation of an MGuardTM stent. CONCLUSION: This case report provides evidence
      that coronary artery aneurysms, even if very large, can be safely treated by
      MGuardTM stent implantation. We strongly emphasize the high flexibility and good
      deliverability of this device, which leads to the complete exclusion of the
      aneurysm mediated by the process of endothelization of its thin mesh sleeves.

PMID- 20682026
TI  - A sequence-based approach to identify reference genes for gene expression
      analysis.
AB  - BACKGROUND: An important consideration when analyzing both microarray and
      quantitative PCR expression data is the selection of appropriate genes as
      endogenous controls or reference genes. This step is especially critical when
      identifying genes differentially expressed between datasets. Moreover, reference
      genes suitable in one context (e.g. lung cancer) may not be suitable in another
      (e.g. breast cancer). Currently, the main approach to identify reference genes
      involves the mining of expression microarray data for highly expressed and
      relatively constant transcripts across a sample set. A caveat here is the
      requirement for transcript normalization prior to analysis, and measurements
      obtained are relative, not absolute. Alternatively, as sequencing-based
      technologies provide digital quantitative output, absolute quantification ensues,
      and reference gene identification becomes more accurate. METHODS: Serial analysis
      of gene expression (SAGE) profiles of non-malignant and malignant lung samples
      were compared using a permutation test to identify the most stably expressed
      genes across all samples. Subsequently, the specificity of the reference genes
      was evaluated across multiple tissue types, their constancy of expression was
      assessed using quantitative RT-PCR (qPCR), and their impact on differential
      expression analysis of microarray data was evaluated. RESULTS: We show that (i)
      conventional references genes such as ACTB and GAPDH are highly variable between
      cancerous and non-cancerous samples, (ii) reference genes identified for lung
      cancer do not perform well for other cancer types (breast and brain), (iii)
      reference genes identified through SAGE show low variability using qPCR in a
      different cohort of samples, and (iv) normalization of a lung cancer gene
      expression microarray dataset with or without our reference genes, yields
      different results for differential gene expression and subsequent analyses.
      Specifically, key established pathways in lung cancer exhibit higher statistical
      significance using a dataset normalized with our reference genes relative to
      normalization without using our reference genes. CONCLUSIONS: Our analyses found
      NDUFA1, RPL19, RAB5C, and RPS18 to occupy the top ranking positions among 15
      suitable reference genes optimal for normalization of lung tissue expression
      data. Significantly, the approach used in this study can be applied to data
      generated using new generation sequencing platforms for the identification of
      reference genes optimal within diverse contexts.

PMID- 20682027
TI  - Different sex ratios of children born to Indian and Pakistani immigrants in
      Norway.
AB  - BACKGROUND: A low female-to-male ratio has been observed in different Asian
      countries, but this phenomenon has not been well studied among immigrants living
      in Western societies. In this study, we investigated whether a low female-to-male
      ratio exists among Indian and Pakistani immigrants living in Norway. In
      particular, we investigated whether the determination of sex via ultrasound
      examination, a common obstetric procedure that has been used in Norway since the
      early 1980 s, has influenced the female-to-male ratio among children born to
      parents of Indian or Pakistani origin. METHODS: We performed a retrospective
      cohort study of live births in mothers of Indian (n = 1597) and Pakistani (n =
      5617) origin. Data were obtained from "Statistics Norway" and the female-to-male
      (F/M) sex ratio was evaluated among 21,325 children born, in increasing birth
      order, during three stratified periods (i.e., 1969-1986, 1987-1996, and 1997
      2005). RESULTS: A significant low female-to-male sex ratio was observed among
      children in the third and fourth birth order (sex ratio 65; 95% CI 51-80) from
      mothers of Indian origin who gave birth after 1987. Sex ratios did not deviate
      from the expected natural variation in the Indian cohort from 1969 to 1986, and
      remained stable in the Pakistani cohort during the entire study period. However,
      the female-to-male sex ratio seemed less skewed in recent years (i.e., 1997
      2005). CONCLUSION: Significant differences were observed in the sex ratio of
      children born to mothers of Indian origin compared with children born to mothers
      of Pakistani origin. A skewed number of female births among higher birth orders
      (i.e., third or later) may partly reflect an increase in sex-selective abortion
      among mothers of Indian origin, although the numbers are too small to draw firm
      conclusions. Further research is needed to explain the observed differences in
      the female-to-male ratio among members of these ethnic groups who reside in
      Norway.

PMID- 20682028
TI  - Predictors of outcome after 6 and 12 months following anthroposophic therapy for
      adult outpatients with chronic disease: a secondary analysis from a prospective
      observational study.
AB  - BACKGROUND: Anthroposophic medicine is a physician-provided complementary therapy
      system involving counselling, artistic and physical therapies, and special
      medications. The purpose of this analysis was to identify predictors of symptom
      improvement in patients receiving anthroposophic treatment for chronic diseases.
      METHODS: 913 adult outpatients from Germany participated in a prospective cohort
      study. Patients were starting anthroposophic treatment for mental (30.4% of
      patients, n = 278/913), musculoskeletal (20.2%), neurological (7.6%),
      genitourinary (7.4%) or respiratory disorders (7.2%) or other chronic
      indications. Stepwise multiple linear regression analysis was performed with the
      improvement of Symptom Score (patients' assessment, 0: not present, 10: worst
      possible) after 6 and 12 months as dependent variables. 61 independent variables
      pertaining to socio-demographics, life style, disease status, co-morbidity,
      health status (SF-36), depression, and therapy factors were analysed. RESULTS:
      Compared to baseline, Symptom Score improved by average 2.53 points (95%
      confidence interval 2.39-2.68, p < 0.001) after six months and by 2.49 points
      (2.32-2.65, p < 0.001) after 12 months. The strongest predictor for improvement
      after six months was baseline Symptom Score, which alone accounted for 25% of the
      variance (total model 32%). Improvement after six months was also positively
      predicted by better physical function, better general health, shorter disease
      duration, higher education level, a diagnosis of respiratory disorders, and by a
      higher therapy goal documented by the physician at baseline; and negatively
      predicted by the number of physiotherapy sessions in the pre-study year and by a
      diagnosis of genitourinary disorders. Seven of these nine variables (not the two
      diagnoses) also predicted improvement after 12 months. When repeating the 0-6
      month analysis on two random subsamples of the original sample, three variables
      (baseline Symptom Score, physical function, general health) remained significant
      predictors in both analyses, and three further variables (education level,
      respiratory disorders, therapy goal) were significant in one analysis.
      CONCLUSION: In adult outpatients receiving anthroposophic treatment for chronic
      diseases, symptom improvement after 6 and 12 months was predicted by baseline
      symptoms, health status, disease duration, education, and therapy goal. Other
      variables were not associated with the outcome. This secondary predictor analysis
      of data from a pre-post study does not allow for causal conclusions; the results
      are hypothesis generating and need verification in subsequent studies.

PMID- 20682029
TI  - Introducing the refined gravity hypothesis of extreme sexual size dimorphism.
AB  - BACKGROUND: Explanations for the evolution of female-biased, extreme Sexual Size
      Dimorphism (SSD), which has puzzled researchers since Darwin, are still
      controversial. Here we propose an extension of the Gravity Hypothesis (i.e., the
      GH, which postulates a climbing advantage for small males) that in conjunction
      with the fecundity hypothesis appears to have the most general power to explain
      the evolution of SSD in spiders so far. In this "Bridging GH" we propose that
      bridging locomotion (i.e., walking upside-down under own-made silk bridges) may
      be behind the evolution of extreme SSD. A biomechanical model shows that there is
      a physical constraint for large spiders to bridge. This should lead to a trade
      off between other traits and dispersal in which bridging would favor smaller
      sizes and other selective forces (e.g. fecundity selection in females) would
      favor larger sizes. If bridging allows faster dispersal, small males would have a
      selective advantage by enjoying more mating opportunities. We predicted that both
      large males and females would show a lower propensity to bridge, and that SSD
      would be negatively correlated with sexual dimorphism in bridging propensity. To
      test these hypotheses we experimentally induced bridging in males and females of
      13 species of spiders belonging to the two clades in which bridging locomotion
      has evolved independently and in which most of the cases of extreme SSD in
      spiders are found. RESULTS: We found that 1) as the degree of SSD increased and
      females became larger, females tended to bridge less relative to males, and that
      2) smaller males and females show a higher propensity to bridge. CONCLUSIONS:
      Physical constraints make bridging inefficient for large spiders. Thus, in
      species where bridging is a very common mode of locomotion, small males, by being
      more efficient at bridging, will be competitively superior and enjoy more mating
      opportunities. This "Bridging GH" helps to solve the controversial question of
      what keeps males small and also contributes to explain the wide range of SSD in
      spiders, as those spider species in which extreme SSD has not evolved but still
      live in tall vegetation, do not use bridging locomotion to disperse.

PMID- 20682030
TI  - Singing teaching as a therapy for chronic respiratory disease--a randomised
      controlled trial and qualitative evaluation.
AB  - BACKGROUND: Despite optimal pharmacological therapy and pulmonary rehabilitation,
      patients with COPD continue to be breathless. There is a need to develop
      additional strategies to alleviate symptoms. Learning to sing requires control of
      breathing and posture and might have benefits that translate into daily life.
      METHODS: To test this hypothesis we performed a randomised controlled trial,
      comparing a six week course of twice weekly singing classes to usual care, in 28
      COPD patients. The experience of singing was assessed in a qualitative fashion,
      through interviews with a psychologist. In addition, we surveyed patients with
      chronic respiratory conditions who participated in a series of open singing
      workshops. RESULTS: In the RCT, the physical component score of the SF36 improved
      in the singers (n = 15) compared to the controls (n = 13); +7.5(14.6) vs. 
      3.8(8.4) p = 0.02. Singers also had a significant fall in HAD anxiety score; 
      1.1(2.7) vs. +0.8(1.7) p = 0.03. Singing did not improve single breath counting,
      breath hold time or shuttle walk distance. In the qualitative element, 8 patients
      from the singing group were interviewed. Positive effects on physical sensation,
      general well-being, community/social support and achievement/efficacy emerged as
      common themes. 150 participants in open workshops completed a questionnaire. 96%
      rated the workshops as "very enjoyable" and 98% thought the workshop had taught
      them something about breathing in a different way. 81% of attendees felt a
      "marked physical difference" after the workshop. CONCLUSION: Singing classes can
      improve quality of life measures and anxiety and are viewed as a very positive
      experience by patients with respiratory disease; no adverse consequences of
      participation were observed. TRIAL REGISTRATION: Current Controlled Trials-
      ISRCTN17544114.

PMID- 20682031
TI  - Improving behaviour in self-testing (IBIS): Study on frequency of use,
      consequences, information needs and use, and quality of currently available
      consumer information (protocol).
AB  - BACKGROUND: Self-tests are available to consumers for more than 25 conditions,
      ranging from infectious diseases to cardiovascular risk factors. Self-tests are
      defined as in-vitro tests on body materials such as blood, urine, faeces, or
      saliva that are initiated by consumers to diagnose a particular disorder or risk
      factor without involving a medical professional. In 2006, 16% of a sample of
      Dutch Internet users had ever used at least one self-test and 17% intended to use
      a self-test in the future. The objectives of this study are to determine (1) the
      frequency of self-test use, (2) the consumers' reasons for using or not using a
      self-test, (3) the information that is used by self-testers in the different self
      test stages and the consumers' interpretation of the quality of this information,
      (4) the consumers' response to self-test results in terms of their confidence in
      the result, reassurance by the test result, and follow-up behaviour, (5) the
      information consumers report to need in the decision making process of using or
      not using a self-test, and in further management on the basis of the self-test
      result, and (6) the quality of the currently available consumer information on a
      selected set of self-tests. METHODS: Mixed methods study with (1) a cross
      sectional study consisting of a two-phase Internet-questionnaire, (2) semi
      structured interviews with self-testers and consumers who intend to use a self
      test, and (3) the assessment of the quality of consumer information of self
      tests. The Health Belief Model and the Theory of Planned Behaviour will serve as
      the theoretical basis for the questionnaires and the interview topic guides.
      CONCLUSIONS: The self-testing area is still in a state of flux and therefore it
      is expected that self-test use will increase in the future. To the best of our
      knowledge, this is the first study which combines quantitative and qualitative
      research to identify consumers' information needs and use concerning self
      testing, and the consumers' actual follow-up behaviour based on the self-test
      result, and simultaneously investigates the quality of the currently available
      consumer information. The results of this study will be used as an input in
      developing consumer information on self-testing.

PMID- 20682032
TI  - Siah1 proteins enhance radiosensitivity of human breast cancer cells.
AB  - BACKGROUND: Siah proteins play an important role in cancer progression. We
      evaluated the effect of Siah1, its splice variants Siah1L and the Siah1 mutant
      with the RING finger deleted (Siah1DeltaR) on radiosensitization of human breast
      cancer cells. METHODS: The status of Siah1 and Siah1L was analysed in five breast
      cancer cell lines. To establish stable cells, SKBR3 cells were transfected with
      Siah1, Siah-1L and Siah1DeltaR. Siah1 function was suppressed by siRNA in MCF-7
      cells. The impact of Siah1 overexpression and silencing on apoptosis,
      proliferation, survival, invasion ability and DNA repair was assessed in SKBR3
      and MCF-7 cells, also in regards to radiation. RESULTS: Siah1 and Siah1L mRNA
      expression was absent in four of five breast cancer cells lines analysed.
      Overexpression of Siah1 and Siah1L enhanced radiation-induced apoptosis in stable
      transfected SKBR3 cells, while Siah1DeltaR failed to show this effect. In
      addition, Siah1 and Siah1L significantly reduced cell clonogenic survival and
      proliferation. Siah1L sensitization enhancement ratio values were over 1.5 and
      4.0 for clonogenic survival and proliferation, respectively, pointing to a highly
      cooperative and potentially synergistic fashion with radiation. Siah1 or Siah1L
      significantly reduced invasion ability of SKBR3 and suppressed Tcf/Lef factor
      activity. Importantly, Siah1 siRNA demonstrated opposite effects in MCF-7 cells.
      Siah1 and Siah1L overexpression resulted in inhibition of DNA repair as inferred
      by increased levels of DNA double-strand breaks in irradiated SKBR3 cells.
      CONCLUSION: Our results reveal for the first time how overexpression of Siah1L
      and Siah1 can determine radiosensitivity of breast cancer cells. These findings
      suggest that development of drugs augmenting Siah1 and Siah1L activity could be a
      novel approach in improving tumor cell kill.

PMID- 20682033
TI  - Alcohol, metabolic risk and elevated serum gamma-glutamyl transferase (GGT) in
      Indigenous Australians.
AB  - BACKGROUND: The interaction between overweight/obesity and alcohol intake on
      liver enzyme concentrations have been demonstrated. No studies have yet examined
      the interaction between metabolic syndrome or multiple metabolic risk factors and
      alcohol intake on liver enzymes. The aim of this study was to examine if alcohol
      consumption modifies the effect of metabolic risk on elevated serum GGT in
      Indigenous Australians. METHODS: Data were from N = 2609 Indigenous Australians
      who participated in a health screening program in rural far north Queensland in
      1999-2000 (44.5% response rate). The individual and interactive effects of
      metabolic risk and alcohol drinking on elevated serum GGT concentrations (>or=50
      U/L) were analyzed using logistic regression. RESULTS: Overall, 26% of the
      population had GGT>or=50 U/L. Elevated GGT was associated with alcohol drinking
      (moderate drinking: OR 2.3 [95%CI 1.6 - 3.2]; risky drinking: OR 6.0 [4.4 -
      8.2]), and with abdominal obesity (OR 3.7 [2.5 - 5.6]), adverse metabolic risk
      cluster profile (OR 3.4 [2.6 - 4.3]) and metabolic syndrome (OR 2.7 [2.1 - 3.5])
      after adjustment for age, sex, ethnicity, smoking, physical activity and BMI. The
      associations of obesity and metabolic syndrome with elevated GGT were similar
      across alcohol drinking strata, but the association of an adverse metabolic risk
      cluster profile with elevated GGT was larger in risky drinkers (OR 4.9 [3.7 -
      6.7]) than in moderate drinkers (OR 2.8 [1.6 - 4.9]) and abstainers (OR 1.6 [0.9 
      2.8]). CONCLUSIONS: In this Indigenous population, an adverse metabolic profile
      conferred three times the risk of elevated GGT in risky drinkers compared with
      abstainers, independent of sex and ethnicity. Community interventions need to
      target both determinants of the population's metabolic status and alcohol
      consumption to reduce the risk of elevated GGT.

PMID- 20682034
TI  - Genetic and functional analysis of HIV-1 Rev Responsive Element (RRE) sequences
      from North-India.
AB  - HIV-1 Rev protein regulates the expression of HIV-1 transcripts by binding to a
      highly structured stem loop structure called the Rev Responsive Element (RRE)
      present in the genomic and partially spliced RNAs. Genetic variation in this
      structure is likely to affect binding of Rev protein and ultimately overall gene
      expression and replication. We characterized RRE sequences from 13 HIV-1 infected
      individuals from North India which also included two mother-child pairs following
      vertical transmission. We observed high degree of conservation of sequences,
      including the 9-nt (CACUAUGGG) long sequence in stem-loop B, required for
      efficient binding of Rev protein. All of our 13 RRE sequences possessed G to A
      (position 66) mutation located in the critical branched-stem-loop B which is not
      present in consensus C or B sequence. We derived a consensus RRE structure which
      showed interesting changes in the stem-loop structures including the stem-loop B.
      Mother-Child RRE sequences showed conservation of unique polymorphisms as well as
      some new mutations in child RRE sequences. Despite these changes, the ability to
      form multiple essential stem-loop structures required for Rev binding was
      conserved. RRE RNA derived from one of the samples, VT5, retained the ability to
      bind Rev protein under in vitro conditions although it showed alternate secondary
      structure. This is the first study from India describing the structural and
      possible functional implications due to very unique RRE sequence heterogeneity
      and its possible role in vertical transmission and gene expression.

PMID- 20682035
TI  - Risk of osteoporotic fracture in a large population-based cohort of patients with
      rheumatoid arthritis.
AB  - INTRODUCTION: Although osteoporosis has been reported to be more common in
      patients with rheumatoid arthritis (RA), little is known whether the risk of
      osteoporotic fractures in these patients differs by age, sex, and anatomic site.
      METHODS: A retrospective cohort study was conducted using a health care
      utilization database. Incidence rates (IRs) and rate ratios (RRs) of osteoporotic
      fractures with 95% confidence intervals (CIs) were calculated. Multivariable Cox
      proportional hazards models compared the risk of osteoporotic fracture at typical
      sites between RA and non-RA patients. RESULTS: During a median 1.63-year follow
      up, 872 (1.9%) of 47,034 RA patients experienced a fracture. The IR for
      osteoporotic fracture at typical sites among RA patients was 9.6 per 1,000 person
      years, 1.5 times higher than the rate of non-RA patients. The IR was highest for
      hip fracture (3.4 per 1,000 person-years) in RA. The IRs across all age groups
      were higher for women than men and increased with older age in both groups. The
      RRs were elevated in RA patients across all common sites of osteoporotic
      fracture: hip (1.62, 95% CI 1.43 to 1.84), wrist (1.15, 95% CI 1.00 to 1.32),
      pelvis (2.02, 95% CI 1.77 to 2.30), and humerus (1.51, 95% CI 1.27 to 1.84).
      After confounding adjustment, a modest increase in risk for fracture was noted
      with RA (hazard ratio 1.26, 95% CI 1.15 to 1.38). CONCLUSIONS: Our study showed
      an increased risk of osteoporotic fractures for RA patients across all age
      groups, sex and various anatomic sites, compared with non-RA patients.

PMID- 20682036
TI  - Impact of the factor V Leiden mutation on the outcome of pneumococcal pneumonia:
      a controlled laboratory study.
AB  - INTRODUCTION: Streptococcus (S.) pneumoniae is the most common cause of community
      acquired pneumonia. The factor V Leiden (FVL) mutation results in resistance of
      activated FV to inactivation by activated protein C and thereby in a
      prothrombotic phenotype. Human heterozygous FVL carriers have been reported to be
      relatively protected against sepsis-related mortality. We here determined the
      effect of the FVL mutation on coagulation, inflammation, bacterial outgrowth and
      outcome in murine pneumococcal pneumonia. METHODS: Wild-type mice and mice
      heterozygous or homozygous for the FVL mutation were infected intranasally with
      2*106 colony forming units of viable S. pneumoniae. Mice were euthanized after 24
      or 48 hours or observed in a survival study. In separate experiments mice were
      treated with ceftriaxone intraperitoneally 24 hours after infection and
      euthanized after 48 hours or observed in a survival study. RESULTS: The FVL
      mutation had no consistent effect on activation of coagulation in either the
      presence or absence of ceftriaxone therapy, as reflected by comparable lung and
      plasma levels of thrombin-antithrombin complexes and fibrin degradation products.
      Moreover, the FVL mutation had no effect on lung histopathology, neutrophil
      influx, cytokine and chemokine levels or bacterial outgrowth. Remarkably,
      homozygous FVL mice were strongly protected against death due to pneumococcal
      pneumonia when treated with ceftriaxone, which was associated with more
      pronounced FXIII depletion; this protective effect was not observed in the
      absence of antibiotic therapy. CONCLUSIONS: Homozygosity for the FVL mutation
      protects against lethality due to pneumococcal pneumonia in mice treated with
      antibiotics.

PMID- 20682037
TI  - The impact of delirium on the prediction of in-hospital mortality in intensive
      care patients.
AB  - INTRODUCTION: Predictive models, such as acute physiology and chronic health
      evaluation II (APACHE-II), are widely used in intensive care units (ICUs) to
      estimate mortality. Although the presence of delirium is associated with a higher
      mortality in ICU patients, delirium is not part of the APACHE-II model. The aim
      of the current study was to evaluate whether delirium, present within 24 hours
      after ICU admission, improves the predictive value of the APACHE-II score.
      METHODS: In a prospective cohort study 2116 adult patients admitted between
      February 2008 and February 2009 were screened for delirium with the confusion
      assessment method-ICU (CAM-ICU). Exclusion criteria were sustained coma and
      unable to understand Dutch. Logistic regression analysis was used to estimate the
      predicted probabilities in the model with and without delirium. Calibration plots
      and the Hosmer-Lemeshow test (HL-test) were used to assess calibration. The
      discriminatory power of the models was analyzed by the area under the receiver
      operating characteristics curve (AUC) and AUCs were compared using the Z-test.
      RESULTS: 1740 patients met the inclusion criteria, of which 332 (19%) were
      delirious at the time of ICU admission or within 24 hours after admission.
      Delirium was associated with in-hospital mortality in unadjusted models, odds
      ratio (OR): 3.22 (95% confidence interval [CI]: 2.23 - 4.66). The OR between the
      APACHE-II and in-hospital mortality was 1.15 (95% CI 1.12 - 1.19) per point. The
      predictive accuracy of the APACHE-II did not improve after adding delirium, both
      in the total group as well as in the subgroup without cardiac surgery patients.
      The AUC of the APACHE model without delirium was 0.77 (0.73 - 0.81) and 0.78
      (0.74 - 0.82) when delirium was added to the model. The z-value was 0.92
      indicating no improvement in discriminative power, and the HL-test and
      calibration plots indicated no improvement in calibration. CONCLUSIONS: Although
      delirium is a significant predictor of mortality in ICU patients, adding delirium
      as an additional variable to the APACHE-II model does not result in an
      improvement in its predictive estimates.

PMID- 20682038
TI  - Herpes simplex virus UL56 interacts with and regulates the Nedd4-family ubiquitin
      ligase Itch.
AB  - BACKGROUND: Herpes simplex virus type 2 (HSV-2) is one of many viruses that
      exploits and modifies the cellular ubiquitin system. HSV-2 expresses the tegument
      protein UL56 that has been implicated in cytoplasmic transport and/or release of
      virions, and is a putative regulatory protein of Nedd4 ubiquitin ligase. In order
      to elucidate the biological function of UL56, this study examined the interaction
      of UL56 with the Nedd4-family ubiquitin ligase Itch and its role in the
      regulation of Itch. Additionally, we assessed the similarity between UL56 and
      regulatory proteins of Itch and Nedd4, Nedd4-family-interactins proteins (Ndfip).
      RESULTS: UL56 interacted with Itch, independent of additional viral proteins, and
      mediated more striking degradation of Itch, compared to Nedd4. Moreover, it was
      suggested that the lysosome pathway as well as the proteasome pathway was
      involved in the degradation of Itch. Other HSV-2 proteins with PY motifs, such as
      VP5 and VP16, did not mediate the degradation of endogenous Itch. Ndfip1 and
      Ndfip2 were similar in subcellular distribution patterns to UL56 and colocalized
      with UL56 in co-transfected cells. CONCLUSIONS: We believe that this is the first
      report demonstrating the interaction of a HSV-specific protein and Itch. Thus,
      UL56 could function as a regulatory protein of Itch. The mechanism, function and
      significance of regulating Itch in HSV-2 infection remain unclear and warrant
      further investigation.

PMID- 20682039
TI  - Current understanding of the relationship between cervical manipulation and
      stroke: what does it mean for the chiropractic profession?
AB  - The understanding of the relationship between cervical manipulative therapy
      (CMT) and vertebral artery dissection and stroke (VADS) has evolved considerably
      over the years. In the beginning the relationship was seen as simple cause
      effect, in which CMT was seen to cause VADS in certain susceptible individuals.
      This was perceived as extremely rare by chiropractic physicians, but as far more
      common by neurologists and others. Recent evidence has clarified the relationship
      considerably, and suggests that the relationship is not causal, but that patients
      with VADS often have initial symptoms which cause them to seek care from a
      chiropractic physician and have a stroke some time after, independent of the
      chiropractic visit.This new understanding has shifted the focus for the
      chiropractic physician from one of attempting to "screen" for "risk of
      complication to manipulation" to one of recognizing the patient who may be having
      VADS so that early diagnosis and intervention can be pursued. In addition, this
      new understanding presents the chiropractic profession with an opportunity to
      change the conversation about CMT and VADS by taking a proactive, public health
      approach to this uncommon but potentially devastating disorder.

PMID- 20682040
TI  - Estimating the individualized HIV-1 genetic barrier to resistance using a
      nelfinavir fitness landscape.
AB  - BACKGROUND: Failure on Highly Active Anti-Retroviral Treatment is often
      accompanied with development of antiviral resistance to one or more drugs
      included in the treatment. In general, the virus is more likely to develop
      resistance to drugs with a lower genetic barrier. Previously, we developed a
      method to reverse engineer, from clinical sequence data, a fitness landscape
      experienced by HIV-1 under nelfinavir (NFV) treatment. By simulation of evolution
      over this landscape, the individualized genetic barrier to NFV resistance may be
      estimated for an isolate. RESULTS: We investigated the association of estimated
      genetic barrier with risk of development of NFV resistance at virological
      failure, in 201 patients that were predicted fully susceptible to NFV at
      baseline, and found that a higher estimated genetic barrier was indeed associated
      with lower odds for development of resistance at failure (OR 0.62 (0.45 - 0.94),
      per additional mutation needed, p = .02). CONCLUSIONS: Thus, variation in
      individualized genetic barrier to NFV resistance may impact effective treatment
      options available after treatment failure. If similar results apply for other
      drugs, then estimated genetic barrier may be a new clinical tool for choice of
      treatment regimen, which allows consideration of available treatment options
      after virological failure.

PMID- 20682041
TI  - A method for automatically extracting infectious disease-related primers and
      probes from the literature.
AB  - BACKGROUND: Primer and probe sequences are the main components of nucleic acid
      based detection systems. Biologists use primers and probes for different tasks,
      some related to the diagnosis and prescription of infectious diseases. The
      biological literature is the main information source for empirically validated
      primer and probe sequences. Therefore, it is becoming increasingly important for
      researchers to navigate this important information. In this paper, we present a
      four-phase method for extracting and annotating primer/probe sequences from the
      literature. These phases are: (1) convert each document into a tree of paper
      sections, (2) detect the candidate sequences using a set of finite state machine
      based recognizers, (3) refine problem sequences using a rule-based expert system,
      and (4) annotate the extracted sequences with their related organism/gene
      information. RESULTS: We tested our approach using a test set composed of 297
      manuscripts. The extracted sequences and their organism/gene annotations were
      manually evaluated by a panel of molecular biologists. The results of the
      evaluation show that our approach is suitable for automatically extracting DNA
      sequences, achieving precision/recall rates of 97.98% and 95.77%, respectively.
      In addition, 76.66% of the detected sequences were correctly annotated with their
      organism name. The system also provided correct gene-related information for
      46.18% of the sequences assigned a correct organism name. CONCLUSIONS: We believe
      that the proposed method can facilitate routine tasks for biomedical researchers
      using molecular methods to diagnose and prescribe different infectious diseases.
      In addition, the proposed method can be expanded to detect and extract other
      biological sequences from the literature. The extracted information can also be
      used to readily update available primer/probe databases or to create new
      databases from scratch.

PMID- 20682042
TI  - Breast cancer incidence and overdiagnosis in Catalonia (Spain).
AB  - INTRODUCTION: Early detection of breast cancer (BC) with mammography may cause
      overdiagnosis and overtreatment, detecting tumors which would remain undiagnosed
      during a lifetime. The aims of this study were: first, to model invasive BC
      incidence trends in Catalonia (Spain) taking into account reproductive and
      screening data; and second, to quantify the extent of BC overdiagnosis. METHODS:
      We modeled the incidence of invasive BC using a Poisson regression model.
      Explanatory variables were: age at diagnosis and cohort characteristics
      (completed fertility rate, percentage of women that use mammography at age 50,
      and year of birth). This model also was used to estimate the background incidence
      in the absence of screening. We used a probabilistic model to estimate the
      expected BC incidence if women in the population used mammography as reported in
      health surveys. The difference between the observed and expected cumulative
      incidences provided an estimate of overdiagnosis. RESULTS: Incidence of invasive
      BC increased, especially in cohorts born from 1940 to 1955. The biggest increase
      was observed in these cohorts between the ages of 50 to 65 years, where the final
      BC incidence rates more than doubled the initial ones. Dissemination of
      mammography was significantly associated with BC incidence and overdiagnosis. Our
      estimates of overdiagnosis ranged from 0.4% to 46.6%, for women born around 1935
      and 1950, respectively. CONCLUSIONS: Our results support the existence of
      overdiagnosis in Catalonia attributed to mammography usage, and the limited
      malignant potential of some tumors may play an important role. Women should be
      better informed about this risk. Research should be oriented towards personalized
      screening and risk assessment tools.

PMID- 20682043
TI  - Regulation of the Aurora-A gene following topoisomerase I inhibition: implication
      of the Myc transcription factor.
AB  - During the G2 phase of the cell cycle, the Aurora-A kinase plays an important
      role in centrosome maturation and progression to mitosis. In this study, we show
      in colorectal cell lines that Aurora-A expression is downregulated in response to
      topoisomerase I inhibition. Using chromatin immunoprecipitation assays, we have
      observed that the Myc transcription factor and its Max binding partner are
      associated with the Aurora-A promoter during the G2 phase of the cell cycle. RNA
      interference experiments indicated that Myc is involved in the regulation of the
      Aurora-A gene. Following topoisomerase I inhibition, the expression of Myc
      decreased whereas Mad was upregulated, and the association of Myc and Max with
      the promoter of the kinase was inhibited. In parallel, an increased association
      of Mad and Miz-1 was detected on DNA, associated with an inhibition of the
      recruitment of transcriptional coactivators. Interestingly, a gain of H3K9
      trimethylation and HP1gamma recruitment was observed on the Aurora-A promoter
      following sn38 treatment, suggesting that this promoter is located within SAHF
      foci following genotoxic treatment. Since Aurora-A is involved in centrosome
      maturation, we observed as expected that topoisomerase I inhibition prevented
      centrosome separation but did not affect their duplication. As a consequence,
      this led to G2 arrest and senescence induction.These results suggest a model by
      which the Aurora-A gene is inactivated by the G2 checkpoint following
      topoisomerase I inhibition. We therefore propose the hypothesis that the
      coordinated overexpression of Myc and Aurora-A, together with a downregulation of
      Mad and Miz-1 should be tested as a prognosis signature of poor responses to
      topoisomerase I inhibitors.

PMID- 20682044
TI  - Epidemiology and economic burden of herpes zoster and post-herpetic neuralgia in
      Italy: a retrospective, population-based study.
AB  - BACKGROUND: Data on the epidemiology and cost of herpes zoster (HZ) and post
      herpetic neuralgia (PHN) in Italy are limited. This retrospective, population
      based study was designed to determine the incidence of HZ and the proportion
      developing PHN in Italy and the associated medical resource utilisation and
      costs. It focused primarily on immunocompetent patients aged > or = 50 years who
      would be eligible for preventive vaccination. METHOD: Data were extracted from a
      primary-care database and national hospital-discharge records covering four major
      regions in Italy for 2003-2005. Cases of HZ and PHN (1 and 3 months' duration;
      PHN1 and PHN3) were identified by ICD9-CM codes and, additionally for PHN,
      prescription of neuropathic pain medication. RESULTS: Over 3 years, 5675 incident
      cases of HZ were documented in adults, of which 3620 occurred in immunocompetent
      patients aged > or = 50 years (incidence of 6.31 per 1000 person-years [95% CI:
      6.01-6.62]). Of the immunocompetent patients aged > or = 50 years with HZ, 9.4%
      (95% CI: 8.2-10.7) and 7.2% (95% CI: 6.2-8.2) developed PHN1 and PHN3,
      respectively. Increasing age, female sex, and being immunologically compromised
      conferred increased risk for both HZ and PHN. Overall, about 1.3% of HZ and
      almost 2% of PHN cases required inpatient care, with 16.9% of all HZ-related
      hospitalisations due specifically to PHN. In patients aged > or = 50 years, mean
      stay was 7.8 +/- 5.4 days for HZ and 10.2 +/- 8.6 days for PHN, and direct costs
      associated with inpatient care were more than 20 times outpatient costs per HZ
      case (mean +/- SD: euro2592 +/- euro1313 vs. euro122.68 +/- euro97.51) and over 5
      times more per episode of PHN (mean +/- SD: euro2806 +/- euro2641 vs. euro446.10
      +/- euro442.97). Total annual costs were euro41.2 million, of which euro28.2
      million were direct costs and euro13.0 million indirect costs. CONCLUSIONS: This
      study, the largest to date on the epidemiology and economic impact of HZ and PHN
      in Italy, confirms the considerable disease and economic burden posed by HZ. As
      HZ and PHN disproportionately affect the elderly, without intervention this
      problem is likely to grow as the proportion of elderly in the Italian population
      continues to increase.

PMID- 20682045
TI  - Molecular characterization and expression of DERL1 in bovine ovarian follicles
      and corpora lutea.
AB  - The endoplasmic reticulum (ER) is a major site of protein synthesis and
      facilitates the folding and assembly of newly synthesized proteins. Misfolded
      proteins are retrotranslocated across the ER membrane and destroyed at the
      proteasome. DERL1 is an important protein involved in the retrotranslocation and
      degradation of a subset of misfolded proteins from the ER. We characterized a
      2617 bp cDNA from bovine granulosa cells that corresponded to bovine DERL1. Two
      transcripts of 3 and 2.6 kb were detected by Northern blot analysis, and showed
      variations in expression among tissues. During follicular development, DERL1
      expression was greater in day 5 dominant follicles compared to small follicles,
      ovulatory follicles, or corpus luteum (CL). Within the CL, DERL1 mRNA expression
      was intermediate in midcycle, and lowest in late cycle as compared to early in
      the estrous cycle. Western blot analyses demonstrated the presence of DERL1 in
      the bovine CL at days 5, 11, and 18 of the estrous cycle. Co-immunoprecipitation
      using luteal tissues showed that DERL1 interacts with class I MHC but not with
      VIMP or p97 ATPase. The interaction between DERL1 and MHC I suggests that, in the
      CL, DERL1 may regulate the integrity of MHC I molecules that are transported to
      the ER membrane. Furthermore, the greater expression of DERL1 mRNA is associated
      with the active follicular development and early luteal stages, suggesting a role
      of DERL1 in tissue remodeling events and maintenance of function in reproductive
      tissues.

PMID- 20682046
TI  - 3'-coterminal subgenomic RNAs and putative cis-acting elements of Grapevine
      leafroll-associated virus 3 reveals 'unique' features of gene expression strategy
      in the genus Ampelovirus.
AB  - BACKGROUND: The family Closteroviridae comprises genera with monopartite genomes,
      Closterovirus and Ampelovirus, and with bipartite and tripartite genomes,
      Crinivirus. By contrast to closteroviruses in the genera Closterovirus and
      Crinivirus, much less is known about the molecular biology of viruses in the
      genus Ampelovirus, although they cause serious diseases in agriculturally
      important perennial crops like grapevines, pineapple, cherries and plums.
      RESULTS: The gene expression and cis-acting elements of Grapevine leafroll
      associated virus 3 (GLRaV-3; genus Ampelovirus) was examined and compared to that
      of other members of the family Closteroviridae. Six putative 3'-coterminal
      subgenomic (sg) RNAs were abundantly present in grapevine (Vitis vinifera)
      infected with GLRaV-3. The sgRNAs for coat protein (CP), p21, p20A and p20B were
      confirmed using gene-specific riboprobes in Northern blot analysis. The 5'
      termini of sgRNAs specific to CP, p21, p20A and p20B were mapped in the 18,498
      nucleotide (nt) virus genome and their leader sequences determined to be 48, 23,
      95 and 125 nt, respectively. No conserved motifs were found around the
      transcription start site or in the leader sequence of these sgRNAs. The predicted
      secondary structure analysis of sequences around the start site failed to reveal
      any conserved motifs among the four sgRNAs. The GLRaV-3 isolate from Washington
      had a 737 nt long 5' nontranslated region (NTR) with a tandem repeat of 65 nt
      sequence and differed in sequence and predicted secondary structure with a South
      Africa isolate. Comparison of the dissimilar sequences of the 5'NTRs did not
      reveal any common predicted structures. The 3'NTR was shorter and more conserved.
      The lack of similarity among the cis-acting elements of the diverse viruses in
      the family Closteroviridae is another measure of the complexity of their
      evolution. CONCLUSIONS: The results indicate that transcription regulation of
      GLRaV-3 sgRNAs appears to be different from members of the genus Closterovirus.
      An analysis of the genome sequence confirmed that GLRaV-3 has an unusually long
      5'NTR of 737 nt compared to other monopartite members of the family
      Closteroviridae, with distinct differences in the sequence and predicted
      secondary structure when compared to the corresponding region of the GLRaV-3
      isolate from South Africa.

PMID- 20682047
TI  - A SNP associated with alternative splicing of RPT5b causes unequal redundancy
      between RPT5a and RPT5b among Arabidopsis thaliana natural variation.
AB  - BACKGROUND: The proteasome subunit RPT5, which is essential for gametophyte
      development, is encoded by two genes in Arabidopsis thaliana; RPT5a and RPT5b. We
      showed previously that RPT5a and RPT5b are fully redundant in the Columbia (Col
      0) accession, whereas in the Wassilewskia accession (Ws-4), RPT5b does not
      complement the effect of a strong rpt5a mutation in the male gametophyte, and
      only partially complements rpt5a mutation in the sporophyte. RPT5bCol-0 and
      RPT5bWs-4 differ by only two SNPs, one located in the promoter and the other in
      the seventh intron of the gene. RESULTS: By exploiting natural variation at RPT5b
      we determined that the SNP located in RPT5b intron seven, rather than the
      promoter SNP, is the sole basis of this lack of redundancy. In Ws-4 this SNP is
      predicted to create a new splicing branchpoint sequence that induces a partial
      mis-splicing of the pre-mRNA, leading to the introduction of a Premature
      Termination Codon. We characterized 5 accessions carrying this A-to-T
      substitution in intron seven and observed a complete correlation between this SNP
      and both a 10 to 20% level of the RPT5b pre-mRNA mis-splicing and the lack of
      ability to complement an rpt5a mutant phenotype. CONCLUSION: The accession
      dependent unequal redundancy between RPT5a and RPT5b genes illustrates an example
      of evolutionary drifting between duplicated genes through alternative splicing.

PMID- 20682048
TI  - Role of DNA methylation in miR-200c/141 cluster silencing in invasive breast
      cancer cells.
AB  - BACKGROUND: The miR-200c/141 cluster has recently been implicated in the
      epithelial to mesenchymal transition (EMT) process. The expression of these two
      miRNAs is inversely correlated with tumorigenicity and invasiveness in several
      human cancers. The role of these miRNAs in cancer progression is based in part on
      their capacity to target the EMT activators ZEB1 and ZEB2, two transcription
      factors, which in turn repress expression of E-cadherin. Little is known about
      the regulation of the mir200c/141 cluster, whose targeting has been proposed as a
      promising new therapy for the most aggressive tumors. FINDINGS: We show that the
      miR-200c/141 cluster is repressed by DNA methylation of a CpG island located in
      the promoter region of these miRNAs. Whereas in vitro methylation of the miR
      200c/141 promoter led to shutdown of promoter activity, treatment with a
      demethylating agent caused transcriptional reactivation in breast cancer cells
      formerly lacking expression of miR-200c and miR-141. More importantly, we
      observed that DNA methylation of the identified miR-200c/141 promoter was tightly
      correlated with phenotype and the invasive capacity in a panel of 8 human breast
      cancer cell lines. In line with this, in vitro induction of EMT by ectopic
      expression of the EMT transcription factor Twist in human immortalized mammary
      epithelial cells (HMLE) was accompanied by increased DNA methylation and
      concomitant repression of the miR-200c/141 locus. CONCLUSIONS: The present study
      demonstrates that expression of the miR-200c/141 cluster is regulated by DNA
      methylation, suggesting epigenetic regulation of this miRNA locus in aggressive
      breast cancer cell lines as well as untransformed mammary epithelial cells. This
      epigenetic silencing mechanism might represent a novel component of the
      regulatory circuit for the maintenance of EMT programs in cancer and normal
      cells.

PMID- 20682049
TI  - Treatment of hypophosphatemia in the intensive care unit: a review.
AB  - INTRODUCTION: Currently no evidence-based guideline exists for the approach to
      hypophosphatemia in critically ill patients. METHODS: We performed a narrative
      review of the medical literature to identify the incidence, symptoms, and
      treatment of hypophosphatemia in critically ill patients. Specifically, we
      searched for answers to the questions whether correction of hypophosphatemia is
      associated with improved outcome, and whether a certain treatment strategy is
      superior. RESULTS: Incidence: hypophosphatemia is frequently encountered in the
      intensive care unit; and critically ill patients are at increased risk for
      developing hypophosphatemia due to the presence of multiple causal factors.
      SYMPTOMS: hypophosphatemia may lead to a multitude of symptoms, including cardiac
      and respiratory failure. TREATMENT: hypophosphatemia is generally corrected when
      it is symptomatic or severe. However, although multiple studies confirm the
      efficacy and safety of intravenous phosphate administration, it remains uncertain
      when and how to correct hypophosphatemia. OUTCOME: in some studies,
      hypophosphatemia was associated with higher mortality; a paucity of randomized
      controlled evidence exists for whether correction of hypophosphatemia improves
      the outcome in critically ill patients. CONCLUSIONS: Additional studies
      addressing the current approach to hypophosphatemia in critically ill patients
      are required. Studies should focus on the association between hypophosphatemia
      and morbidity and/or mortality, as well as the effect of correction of this
      electrolyte disorder.

PMID- 20682050
TI  - Field efficacy of pyrethroid treated plastic sheeting (durable lining) in
      combination with long lasting insecticidal nets against malaria vectors.
AB  - BACKGROUND: Insecticide treated plastic sheeting (ITPS), sometimes known as
      durable lining, has potential as a long-lasting insecticidal surface for malaria
      vector control when used as lining for interior walls and ceilings inside the
      home. Against a backdrop of increasing long lasting net (LN) coverage, we
      examined the effect of combining permethrin-treated plastic sheeting (ITPS) with
      LNs in Burkina Faso. METHODS: A verandah trap experimental hut trial of ITPS with
      or without Olyset LN was conducted in the Vallee du Kou near Bobo-Dioulasso,
      where the two molecular forms of Anopheles gambiae s.s., S (frequency 65%) and M
      (frequency 35%), occur. The S form is mostly pyrethroid resistant (Fkdr = 92%)
      owing to the kdr mechanism, and the M form is mostly kdr susceptible (Fkdr = 7%).
      The treatment arms included ITPS, Olyset, ITPS plus Olyset, ITPS plus untreated
      net (with or without holes), and untreated control. RESULTS: ITPS was
      significantly inferior to Olyset LN in terms of mortality (37% vs 63%), blood
      feeding inhibition (20% vs 81%) and deterrence (0 vs 42%) effects, and hence
      altogether inferior as a means of personal protection (16% vs 89%). The addition
      of ITPS to Olyset did not improve mortality (62%), blood feeding inhibition
      (75%), deterrence (50%) or personal protection (88%) over that of Olyset used
      alone. Use of untreated nets - both holed and intact - with ITPS provided greater
      protection from blood-feeding. The intact net/ITPS combination killed more
      mosquitoes than ITPS on its own. CONCLUSIONS: Although ITPS has a potential role
      for community control of malaria, at low coverage it is unlikely to be as good as
      Olyset LNs for household protection. The combination of pyrethroid IRS and
      pyrethroid LN - as practiced in some countries - is unlikely to be additive
      except, perhaps, at high levels of IRS coverage. A combination of LN and ITPS
      treated with an alternative insecticide is likely to be more effective,
      particularly in areas of pyrethroid resistance.

PMID- 20682052
TI  - Health promotion at local level: a case study of content, organization and
      development in four Swedish municipalities.
AB  - BACKGROUND: Several health determinants are related to local conditions and
      prerequisites at community level. For this reason, strengthening community action
      has been one of five strategies implemented in health promotion since the end of
      the 1980s. Such action includes setting priorities, making decisions, planning
      strategies, and implementing them to achieve better health. The aim of this paper
      is to obtain a deeper understanding of content, organization and processes in the
      development of local health promotion. METHODS: A qualitative multiple case study
      of four Swedish municipalities. The cases were analyzed in accordance with the
      principles of cross-case study analysis, and a content analysis of documents and
      interviews was conducted in two steps. First, a manifest content analysis was
      performed to identify present and former actors and measures. Thereafter, a
      latent content analysis was performed to investigate structures and processes in
      local contexts. RESULTS: The results of the inductive content analysis showed
      development of local health promotion in three phases: initiation, action, and
      achievement. Strengthening factors were local actors, health statistics and
      events. Hindering factors were lack of resources and vague objectives. External
      factors, e.g. national policies, were not perceived as prominent influencing
      factors. Media reports were regarded as having had an influence, but only to some
      extent. The content of local health promotion has developed from ad-hoc lifestyle
      and behaviour-related actions into structural, intersectoral actions related to
      determinants of health. CONCLUSIONS: The municipalities have organized and
      developed their health promotion targets, actions and priorities on the basis of
      local needs and prerequisites. The three phases in the identified health
      promotion processes were experienced and documented as being subject to greater
      influence from internal rather than external strengthening and hindering factors
      in their local contexts.

PMID- 20682051
TI  - Human genetic differentiation across the Strait of Gibraltar.
AB  - BACKGROUND: The Strait of Gibraltar is a crucial area in the settlement history
      of modern humans because it represents a possible connection between Africa and
      Europe. So far, genetic data were inconclusive about the fact that this strait
      constitutes a barrier to gene flow, as previous results were highly variable
      depending on the genetic locus studied. The present study evaluates the impact of
      the Gibraltar region in reducing gene flow between populations from North-Western
      Africa and South-Western Europe, by comparing formally various genetic loci.
      First, we compute several statistics of population differentiation. Then, we use
      an original simulation approach in order to infer the most probable evolutionary
      scenario for the settlement of the area, taking into account the effects of both
      demography and natural selection at some loci. RESULTS: We show that the genetic
      patterns observed today in the region of the Strait of Gibraltar may reflect an
      ancient population genetic structure which has not been completely erased by more
      recent events such as Neolithic migrations. Moreover, the differences observed
      among the loci (i.e. a strong genetic boundary revealed by the Y-chromosome
      polymorphism and, at the other extreme, no genetic differentiation revealed by
      HLA-DRB1 variation) across the strait suggest specific evolutionary histories
      like sex-mediated migration and natural selection. By considering a model of
      balancing selection for HLA-DRB1, we here estimate a coefficient of selection of
      2.2% for this locus (although weaker in Europe than in Africa), which is in line
      with what was estimated from synonymous versus non-synonymous substitution rates.
      Selection at this marker thus appears strong enough to leave a signature not only
      at the DNA level, but also at the population level where drift and migration
      processes were certainly relevant. CONCLUSIONS: Our multi-loci approach using
      both descriptive analyses and Bayesian inferences lead to better characterize the
      role of the Strait of Gibraltar in the evolution of modern humans. We show that
      gene flow across the Strait of Gibraltar occurred at relatively high rates since
      pre-Neolithic times and that natural selection and sex-bias migrations distorted
      the demographic signal at some specific loci of our genome.

PMID- 20682053
TI  - Safety evaluation of allogeneic umbilical cord blood mononuclear cell therapy for
      degenerative conditions.
AB  - BACKGROUND: The current paradigm for cord blood transplantation is that HLA
      matching and immune suppression are strictly required to prevent graft versus
      host disease (GVHD). Immunological arguments and historical examples have been
      made that the use of cord blood for non-hematopoietic activities such as growth
      factor production, stimulation of angiogenesis, and immune modulation may not
      require matching or immune suppression. METHODS: 114 patients suffering from non
      hematopoietic degenerative conditions were treated with non-matched, allogeneic
      cord blood. Doses of 1-3 x 10(7) cord blood mononuclear cells per treatment, with
      4-5 treatments both intrathecal and intravenously were performed. Adverse events
      and hematological, immunological, and biochemical parameters were analyzed for
      safety evaluation. RESULTS: No serious adverse effects were reported.
      Hematological, immunological, and biochemical parameters did not deviate from
      normal ranges as a result of therapy. CONCLUSION: The current hematology-based
      paradigm of need for matching and immune suppression needs to be revisited when
      cord blood is used for non-hematopoietic regenerative purposes in immune
      competent recipients.

PMID- 20682055
TI  - Four small supernumerary marker chromosomes derived from chromosomes 6, 8, 11 and
      12 in a patient with minimal clinical abnormalities: a case report.
AB  - INTRODUCTION: Small supernumerary marker chromosomes are still a problem in
      cytogenetic diagnostic and genetic counseling. This holds especially true for the
      rare cases with multiple small supernumerary marker chromosomes. Most such cases
      are reported to be clinically severely affected due to the chromosomal imbalances
      induced by the presence of small supernumerary marker chromosomes. Here we report
      the first case of a patient having four different small supernumerary marker
      chromosomes which, apart from slight developmental retardation in youth and non
      malignant hyperpigmentation, presented no other clinical signs. CASE
      PRESENTATION: Our patient was a 30-year-old Caucasian man, delivered by caesarean
      section because of macrosomy. At birth he presented with bilateral cryptorchidism
      but no other birth defects. At age of around two years he showed psychomotor
      delay and a bilateral convergent strabismus. Later he had slight learning
      difficulties, with normal social behavior and now lives an independent life as an
      adult. Apart from hypogenitalism, he has multiple hyperpigmented nevi all over
      his body, short feet with pes cavus and claw toes. At age of 30 years,
      cytogenetic and molecular cytogenetic analysis revealed a karyotype of
      50,XY,+min(6)(:p11.1-> q11.1:),+min(8)(:p11.1->q11.1:),+min(11)(:p11.11
      >q11:),+min(12)(:p11.2~12->q10:), leading overall to a small partial trisomy in
      12p11.1~12.1. CONCLUSIONS: Including this case, four single case reports are
      available in the literature with a karyotype 50,XN,+4mar. For prenatally detected
      multiple small supernumerary marker chromosomes in particular we learn from this
      case that such a cytogenetic condition may be correlated with a positive clinical
      outcome.

PMID- 20682054
TI  - Dynamics of dendritic cell maturation are identified through a novel filtering
      strategy applied to biological time-course microarray replicates.
AB  - BACKGROUND: Dendritic cells (DC) play a central role in primary immune responses
      and become potent stimulators of the adaptive immune response after undergoing
      the critical process of maturation. Understanding the dynamics of DC maturation
      would provide key insights into this important process. Time course microarray
      experiments can provide unique insights into DC maturation dynamics. Replicate
      experiments are necessary to address the issues of experimental and biological
      variability. Statistical methods and averaging are often used to identify
      significant signals. Here a novel strategy for filtering of replicate time course
      microarray data, which identifies consistent signals between the replicates, is
      presented and applied to a DC time course microarray experiment. RESULTS: The
      temporal dynamics of DC maturation were studied by stimulating DC with poly(I:C)
      and following gene expression at 5 time points from 1 to 24 hours. The novel
      filtering strategy uses standard statistical and fold change techniques, along
      with the consistency of replicate temporal profiles, to identify those
      differentially expressed genes that were consistent in two biological replicate
      experiments. To address the issue of cluster reproducibility a consensus
      clustering method, which identifies clusters of genes whose expression varies
      consistently between replicates, was also developed and applied. Analysis of the
      resulting clusters revealed many known and novel characteristics of DC
      maturation, such as the up-regulation of specific immune response pathways.
      Intriguingly, more genes were down-regulated than up-regulated. Results identify
      a more comprehensive program of down-regulation, including many genes involved in
      protein synthesis, metabolism, and housekeeping needed for maintenance of
      cellular integrity and metabolism. CONCLUSIONS: The new filtering strategy
      emphasizes the importance of consistent and reproducible results when analyzing
      microarray data and utilizes consistency between replicate experiments as a
      criterion in both feature selection and clustering, without averaging or
      otherwise combining replicate data. Observation of a significant down-regulation
      program during DC maturation indicates that DC are preparing for cell death and
      provides a path to better understand the process. This new filtering strategy can
      be adapted for use in analyzing other large-scale time course data sets with
      replicates.

PMID- 20682056
TI  - Time and time again: unisexual salamanders (genus Ambystoma) are the oldest
      unisexual vertebrates.
AB  - BACKGROUND: The age of unisexual salamanders of the genus Ambystoma is
      contentious. Recent and ancient evolutionary histories of unisexual Ambystoma
      were proposed by a few separate studies that constructed phylogenies using
      mitochondrial DNA markers (cytochrome b gene vs. non-coding region). In contrast
      to other studies showing that unisexual Ambystoma represent the most ancient
      unisexual vertebrates, a recent study by Robertson et al. suggests that this
      lineage has a very recent origin of less than 25,000 years ago. RESULTS: We re
      examined the phylogenetic relationship of the unisexuals to A. barbouri from
      various populations using both mitochondrial markers as well as the complete
      mitochondrial genomes of A. barbouri and a unisexual individual from Kentucky.
      Lineage dating was conducted using BEAST and MultiDivTime on a complete
      mitochondrial genome phylogeny. Our results support a monophyletic lineage for
      unisexual Ambystoma that shares its most recent common ancestor with an A.
      barbouri lineage from western Kentucky. In contrast to the Robertson et al.'s
      study, no A. barbouri individual shared an identical or almost identical
      cytochrome b haplotype with any unisexual. Molecular dating supports an early
      Pliocene origin for the unisexual linage (approximately 5 million years ago). We
      propose that a unisexual-like cytochrome b numt (or pseudogene) exists in the
      controversial A. barbouri individuals from Kentucky, which was likely the cause
      of an erroneous phylogeny and time estimate in Robertson et al.'s study.
      CONCLUSION: We reject a recent origin of unisexual Ambystoma and provide strong
      evidence that unisexual Ambystoma are the most ancient unisexual vertebrates
      known to exist. The likely presence of an ancient cytochrome b numt in some
      Kentucky A. barbouri represents a molecular "fossil" reinforcing the hypothesis
      that these individuals are some of the closest extant relatives to unisexual
      Ambystoma.

PMID- 20682057
TI  - Accelerometer profiles of physical activity and inactivity in normal weight,
      overweight, and obese U.S. men and women.
AB  - BACKGROUND: The 2005-2006 National Health and Nutrition Examination Survey
      (NHANES) is used to describe an accelerometer-derived physical
      activity/inactivity profile in normal weight (BMI < 25 kg/m2), overweight (25 </=
      BMI < 30 kg/m2), and obese (BMI >/= 30 kg/m2) U.S. adults. METHODS: We computed
      physical activity volume indicators (activity counts/day, uncensored and censored
      steps/day), rate indicators (e.g., steps/minute), time indicators (employing
      NHANES activity counts/minute cut points to infer time in non-wear, sedentary,
      low, light, moderate, and vigorous intensities), the number of breaks in
      sedentary time (occasions when activity counts rose from < 100 activity/counts in
      one minute to >/= 100 activity counts in the subsequent minute), achievement of
      public health guidelines, and classification by step-defined physical activity
      levels. Data were examined for evidence of consistent and significant gradients
      across BMI-defined categories. RESULTS: In 2005-2006, U.S adults averaged 6,564
      +/- SE 107 censored steps/day, and after considering non-wear time, they spent
      approximately 56.8% of the rest of the waking day in sedentary time, 23.7% in low
      intensity, 16.7% in light intensity, 2.6% in moderate intensity, and 0.2% in
      vigorous intensity. Overall, approximately 3.2% of U.S. adults achieved public
      health guidelines. The normal weight category took 7,190 +/- SE 157 steps/day,
      and spent 25.7 +/- 0.9 minutes/day in moderate intensity and 7.3 +/- 0.4
      minutes/day in vigorous intensity physical activity. The corresponding numbers
      for the overweight category were 6,879 +/- 140 steps/day, 25.3 +/- 0.9
      minutes/day, and 5.3 +/- 0.5 minutes/day and for the obese category 5,784 +/- 124
      steps/day, 17.3 +/- 0.7 minutes/day and 3.2 +/- 0.4 minutes/day. Across BMI
      categories, increasing gradients and significant trends were apparent in males
      for sedentary time and decreasing gradients and significant trends were evident
      in time spent in light intensity, moderate intensity, and vigorous intensity. For
      females, there were only consistent gradients and significant trends apparent for
      decreasing amounts of time spent in moderate and vigorous intensity. CONCLUSIONS:
      Simple indicators of physical activity volume (i.e., steps/day) and time in
      light, moderate or vigorous intensity physical activity differ across BMI
      categories for both sexes, suggesting that these should continue to be targets
      for surveillance.

PMID- 20682058
TI  - Enhancement drugs: are there limits to what we should enhance and why?
AB  - Substances, such as alcohol, opiates and cannabis, have been used by humans for
      millennia. Today, a much wider range of substances are used for a range of
      purposes, including the enhancement of performance during university studies,
      sexual experiences, sports, exercise, at celebrations, socializing and the
      experience of art and music. Substance use is also associated with a range of
      harmful effects to the individual and society as a whole. Prohibitions,
      regulation, prevention and treatment have all been used to protect against this
      harm. In this commentary, it is argued that public health interventions should
      target relevant harms and not to evaluate which aspects of human endeavors and
      experiences should be enhanced and which should not. It is argued that
      interventions should directly target the harmful effects, using the best
      available evidence. Two examples are given of substances that may be altered to
      prevent serious harm--one for alcohol and one for cannabis. In the case of
      alcohol, the addition of dissolved oxygen could reduce both the risk of accidents
      and the risk of liver damage associated with alcohol consumption. In the case of
      cannabis, there is strong indication that the reduction of content Delta
      tetrahydrocannabinol and the increase of cannabidiol could reduce the risk of
      psychoses and the addiction associated with its use. The aim of this article is
      to show that responsible regulation should not necessarily be restricted to
      preventing the use and/or (in the case of alcohol) a reduction in the amounts and
      frequency of its use, but should also aim to include a range of other strategies
      that could reduce the burden of illness associated with illicit substance use.

PMID- 20682059
TI  - Mortality associated with administration of high-dose tranexamic acid and
      aprotinin in primary open-heart procedures: a retrospective analysis.
AB  - INTRODUCTION: Antifibrinolytic agents are commonly used during cardiac surgery to
      minimize bleeding. Because of safety concerns, aprotinin was withdrawn from the
      market in 2007. Since then, tranexamic acid (TXA) has become the antifibrinolytic
      treatment of choice in many heart centers. The safety profile of TXA has not been
      extensively studied. Therefore, the aim of this study was to evaluate safety and
      efficiency of TXA compared with aprotinin in cardiac surgery. METHODS: Since July
      1, 2006, TXA has been administered at a dose of 50 mg/kg tranexamic acid before
      cardiopulmonary bypass (CPB) and 50 mg/kg into the priming fluid of the CPB.
      Prior to this, all patients were treated with aprotinin at a dose of 50,000 KIU
      per kilogram body weight. Safety was evaluated with mortality, biomarkers, and
      the diagnosis of myocardial infarction, ischemic stroke, convulsive seizures, and
      acute renal failure in the intensive care unit (ICU), intermediate care unit
      (IMCU), and hospital stay. Efficiency was evaluated by the need for transfusion
      of blood products and total postoperative blood loss. RESULTS: After informed
      consent, 893 patients were included in our database (557 consecutive patients
      receiving aprotinin and 336 patients receiving TXA). A subgroup of 320 patients
      undergoing open-heart procedures (105 receiving TXA and 215 receiving aprotinin)
      was analyzed separately. In the aprotinin group, a higher rate of late events of
      ischemic stroke (3.4% versus 0.9%; P = 0.02) and neurologic disability (5.8%
      versus 2.4%; P = 0.02) was found. The rate of postoperative convulsive seizures
      was increased in tendency in patients receiving TXA (2.7% versus 0.9%; P = 0.05).
      The use of TXA was associated with higher cumulative drainage losses (PANOVA <
      0.01; Ptime < 0.01) and a higher rate of repeated thoracotomy for bleeding (6.9%
      versus 2.4%; P < 0.01). In the subgroup of patients with open-chamber procedures,
      mortality was higher in the TXA group (16.2% TXA versus 7.5% aprotinin; P =
      0.02). Multivariate logistic regression identified EURO score II and CPB time as
      additional risk factors for this increased mortality. CONCLUSIONS: The use of
      high-dose TXA is questioned, as our data suggest an association between higher
      mortality and minor efficiency while the safety profile of this drug is not
      consistently improved. Further confirmatory prospective studies evaluating the
      efficacy and safety profile of TXA are urgently needed to find a safe dosage for
      this antifibrinolytic drug.

PMID- 20682060
TI  - Generation of human induced pluripotent stem cells by simple transient
      transfection of plasmid DNA encoding reprogramming factors.
AB  - BACKGROUND: The use of lentiviruses to reprogram human somatic cells into induced
      pluripotent stem (iPS) cells could limit their therapeutic usefulness due to the
      integration of viral DNA sequences into the genome of the recipient cell. Recent
      work has demonstrated that human iPS cells can be generated using episomal
      plasmids, excisable transposons, adeno or sendai viruses, mRNA, or recombinant
      proteins. While these approaches offer an advance, the protocols have some
      drawbacks. Commonly the procedures require either subcloning to identify human
      iPS cells that are free of exogenous DNA, a knowledge of virology and safe
      handling procedures, or a detailed understanding of protein biochemistry.
      RESULTS: Here we report a simple approach that facilitates the reprogramming of
      human somatic cells using standard techniques to transfect expression plasmids
      that encode OCT4, NANOG, SOX2, and LIN28 without the need for episomal stability
      or selection. The resulting human iPS cells are free of DNA integration, express
      pluripotent markers, and form teratomas in immunodeficient animals. These iPS
      cells were also able to undergo directed differentiation into hepatocyte-like and
      cardiac myocyte-like cells in culture. CONCLUSIONS: Simple transient transfection
      of plasmid DNA encoding reprogramming factors is sufficient to generate human iPS
      cells from primary fibroblasts that are free of exogenous DNA integrations. This
      approach is highly accessible and could expand the use of iPS cells in the study
      of human disease and development.

PMID- 20682061
TI  - Utility of clinical assessment, imaging, and cryptococcal antigen titer to
      predict AIDS-related complicated forms of cryptococcal meningitis.
AB  - BACKGROUND: This study aimed to evaluate the prevalence and predictors of AIDS
      related complicated cryptococcal meningitis. The outcome was complicated
      cryptococcal meningitis: prolonged (>/= 14 days) altered mental status,
      persistent (>/= 14 days) focal neurologic findings, cerebrospinal fluid (CSF)
      shunt placement or death. Predictor variable operating characteristics were
      estimated using receiver operating characteristic curve (ROC) analysis.
      Multivariate analysis identified independent predictors of the outcome. RESULTS:
      From 1990-2009, 82 patients with first episode of cryptococcal meningitis were
      identified. Of these, 14 (17%) met criteria for complicated forms of cryptococcal
      meningitis (prolonged altered mental status 6, persistent focal neurologic
      findings 7, CSF surgical shunt placement 8, and death 5). Patients with
      complicated cryptococcal meningitis had higher frequency of baseline focal
      neurological findings, head computed tomography (CT) abnormalities, mean CSF
      opening pressure, and cryptococcal antigen (CRAG) titers in serum and CSF. ROC
      area of log2 serum and CSF CRAG titers to predict complicated forms of
      cryptococcal meningitis were comparable, 0.78 (95%CI: 0.66 to 0.90) vs. 0.78 (95%
      CI: 0.67 to 0.89), respectively (chi2, p = 0.95). The ROC areas to predict the
      outcomes were similar for CSF pressure and CSF CRAG titers. In a multiple
      logistic regression model, the following were significant predictors of the
      outcome: baseline focal neurologic findings, head CT abnormalities and log2 CSF
      CRAG titer. CONCLUSIONS: During initial clinical evaluation, a focal neurologic
      exam, abnormal head CT and large cryptococcal burden measured by CRAG titer are
      associated with the outcome of complicated cryptococcal meningitis following 2
      weeks from antifungal therapy initiation.

PMID- 20682062
TI  - Diabetic ketoacidosis complicated by the use of ecstasy: a case report.
AB  - INTRODUCTION: Ecstasy (3,4-methylenedioxymethamphetamin), a hallucinogenic
      amphetamine, is often used by young people, especially at 'raves'. This illicit
      drug can cause many metabolic changes and its use, when associated with prolonged
      exercise, may exacerbate ketoacidosis in type 1 diabetic patients. CASE
      PRESENTATION: This is a case of ketoacidosis complicated by the use of ecstasy in
      a 19-year-old insulin-dependent diabetic Caucasian woman. CONCLUSION: The use of
      ecstasy may trigger diabetic ketoacidosis in patients with a preexisting
      metabolic disorder.

PMID- 20682063
TI  - Non-uniform recovery of left ventricular transmural mechanics in ST-segment
      elevation myocardial infarction.
AB  - BACKGROUND: After a transient ischemic episode, the subendocardial region is more
      severely injured than outer subepicardial layers and may regain a proportionately
      greater degree of mechanical function in the longitudinal direction. We sought to
      explore left ventricular (LV) transmural mechanics in patients with ST-segment
      elevation myocardial infarction (STEMI) for determining the mechanism underlying
      recovery of global LV function after primary percutaneous coronary intervention
      (PCI). METHODS: A total of 42 patients (62 +/- 11 years old, 71% male) with a
      first STEMI underwent serial assessments of LV longitudinal, circumferential and
      radial strains (LS, CS and RS) by selective tracking of subendocardial and
      subepicardial regions within 48 hours and a median of 5 months after PCI. LV
      mechanical parameters were compared with sixteen age and gender matched normal
      controls. RESULTS: In comparison with controls, endocardial and epicardial LS
      were markedly attenuated at 48 hours following PCI (P < 0.001). An improvement in
      LV ejection fraction (EF > 5%) following PCI was seen in 24 (57%) patients and
      was associated with improvement in endocardial and epicardial LS (P < 0.001 and P
      = 0.003, respectively) and endocardial CS (P = 0.01). Radial strain and wall
      motion score index, however, remained persistently abnormal. The change in
      endocardial LS (OR 1.2, 95% CI 1.03 to 1.42, P = 0.01) and the change in
      epicardial LS (OR 1.2, 95% 1.03 to 1.46, P = 0.02) were significantly associated
      with the improvement in LVEF, independent of the location of STEMI and the
      presence of underlying multivessel disease. CONCLUSIONS: In patients with STEMI
      treated by PCI, the recovery of LV subendocardial shortening strain seen in the
      longitudinal direction underlies the improvement in LV global function despite
      persistent abnormalities in radial mechanics and wall motion score index.

PMID- 20682064
TI  - Sudden cardiac death athletes: a systematic review.
AB  - Previous events evidence that sudden cardiac death (SCD) in athletes is still a
      reality and it keeps challenging cardiologists. Considering the importance of SCD
      in athletes and the requisite for an update of this matter, we endeavored to
      describe SCD in athletes. The Medline (via PubMed) and SciELO databases were
      searched using the subject keywords "sudden death, athletes and mortality". The
      incidence of SCD is expected at one case for each 200,000 young athletes per
      year. Overall it is resulted of complex dealings of factors such as
      arrhythmogenic substrate, regulator and triggers factors. In great part of deaths
      caused by heart disease in athletes younger than 35 years old investigations
      evidence cardiac congenital abnormalities. Athletes above 35 years old possibly
      die due to impairments of coronary heart disease, frequently caused by
      atherosclerosis. Myocardial ischemia and myocardial infarction are responsible
      for the most cases of SCD above this age (80%). Pre-participatory athletes'
      evaluation helps to recognize situations that may put the athlete's life in risk
      including cardiovascular diseases. In summary, cardiologic examinations of
      athletes' pre-competition routine is an important way to minimize the risk of
      SCD.

PMID- 20682065
TI  - Scarless and sequential gene modification in Pseudomonas using PCR product
      flanked by short homology regions.
AB  - BACKGROUND: The lambda Red recombination system has been used to inactivate
      chromosomal genes in various bacteria and fungi. The procedure consists of
      electroporating a polymerase chain reaction (PCR) fragment containing antibiotic
      cassette flanked by homology regions to the target locus into a strain that can
      express the lambda Red proteins (Gam, Bet, Exo). RESULTS: Here a scarless gene
      modification strategy based on the Red recombination system has been developed to
      modify Pseudomonas genome DNA via sequential deletion of multiple targets. This
      process was mediated by plasmid pRKaraRed encoding the Red proteins regulated by
      PBAD promoter, which was functional in P. aeruginosa as well as in other
      bacteria. First the target gene was substituted for the sacB-bla cassette flanked
      by short homology regions (50 bp), and then this marker gene cassette could be
      replaced by the PCR fragment flanking itself, generating target-deleted genome
      without any remnants and no change happened to the surrounding region. Twenty
      genes involved in the synthesis and regulation pathways of the phenazine
      derivate, pyocyanin, were modified, including one single-point mutation and
      deletion of two large operons. The recombination efficiencies ranged from 88% to
      98%. Multiple-gene modification was also achieved, generating a triple-gene
      deletion strain PCA (PAO1, DeltaphzHDeltaphzMDeltaphzS), which could produce
      another phenazine derivate, phenazine-1-carboxylic acid (PCA), efficiently and
      exclusively. CONCLUSIONS: This lambda Red-based technique can be used to generate
      scarless and sequential gene modification mutants of P. aeruginosa efficiently,
      using one-step PCR product flanked by short homology regions. Single-point
      mutation, scarless deletion of genes can be achieved easily in less than three
      days. This method may give a new way to construct genetically modified P.
      aeruginosa strains more efficiently and advance the regulatory network study of
      this organism.

PMID- 20682066
TI  - Homeobox transcription factor muscle segment homeobox 2 (Msx2) correlates with
      good prognosis in breast cancer patients and induces apoptosis in vitro.
AB  - INTRODUCTION: The homeobox-containing transcription factor muscle segment
      homeobox 2 (Msx2) plays an important role in mammary gland development. However,
      the clinical implications of Msx2 expression in breast cancer are unclear. The
      aims of this study were to investigate the potential clinical value of Msx2 as a
      breast cancer biomarker and to clarify its functional role in vitro. METHODS:
      Msx2 gene expression was first examined in a well-validated breast cancer
      transcriptomic dataset of 295 patients. Msx2 protein expression was then
      evaluated by immunohistochemistry in a tissue microarray (TMA) containing 281
      invasive breast tumours. Finally, to assess the functional role of Msx2 in vitro,
      Msx2 was ectopically expressed in a highly invasive breast tumour cell line (MDA
      MB-231) and an immortalised breast cell line (MCF10a), and these cell lines were
      examined for changes in growth rate, cell death and cell signalling. RESULTS:
      Examination of Msx2 mRNA expression in a breast cancer transcriptomic dataset
      demonstrated that increased levels of Msx2 were associated with good prognosis (P
      = 0.011). Evaluation of Msx2 protein expression on a TMA revealed that Msx2 was
      detectable in both tumour cell nuclei and cytoplasm. Cytoplasmic Msx2 expression
      was associated with low grade tumours (P = 0.012) and Ki67 negativity (P =
      0.018). Nuclear Msx2 correlated with low-grade tumours (P = 0.015), estrogen
      receptor positivity (P = 0.038), low Ki67 (P = 0.005) and high cyclin D1
      expression (P = 0.037). Increased cytoplasmic Msx2 expression was associated with
      a prolonged breast cancer-specific survival (P = 0.049), recurrence-free survival
      (P = 0.029) and overall survival (P = 0.019). Ectopic expression of Msx2 in
      breast cell lines resulted in radically decreased cell viability mediated by
      induction of cell death via apoptosis. Further analysis of Msx2-expressing cells
      revealed increased levels of p21 and phosphorylated extracellular signal
      regulated kinase (ERK) and decreased levels of Survivin and the 'split ends'
      (SPEN) protein family member RBM15. CONCLUSIONS: We conclude that increased Msx2
      expression results in improved outcome for breast cancer patients, possibly by
      increasing the likelihood of tumour cell death by apoptosis.

PMID- 20682067
TI  - Alpha-santalol, a chemopreventive agent against skin cancer, causes G2/M cell
      cycle arrest in both p53-mutated human epidermoid carcinoma A431 cells and p53
      wild-type human melanoma UACC-62 cells.
AB  - BACKGROUND: alpha-Santalol, an active component of sandalwood oil, has shown
      chemopreventive effects on skin cancer in different murine models. However,
      effects of alpha-santalol on cell cycle have not been studied. Thus, the
      objective of this study was to investigate effects of alpha-santalol on cell
      cycle progression in both p53 mutated human epidermoid carcinoma A431 cells and
      p53 wild-type human melanoma UACC-62 cells to elucidate the mechanism(s) of
      action. METHODS: MTT assay was used to determine cell viability in A431 cells and
      UACC-62; fluorescence-activated cell sorting (FACS) analysis of propidium iodide
      staining was used for determining cell cycle distribution in A431 cells and UACC
      62 cells; immunoblotting was used for determining the expression of various
      proteins and protein complexes involved in the cell cycle progression; siRNA were
      used to knockdown of p21 or p53 in A431 and UACC-62 cells and immunofluorescence
      microscopy was used to investigate microtubules in UACC-62 cells. RESULTS: alpha
      Santalol at 50-100 muM decreased cell viability from 24 h treatment and alpha
      santalol at 50 muM-75 muM induced G2/M phase cell cycle arrest from 6 h treatment
      in both A431 and UACC-62 cells. alpha-Santalol altered expressions of cell cycle
      proteins such as cyclin A, cyclin B1, Cdc2, Cdc25c, p-Cdc25c and Cdk2. All of
      these proteins are critical for G2/M transition. alpha-Santalol treatment up
      regulated the expression of p21 and suppressed expressions of mutated p53 in A431
      cells; whereas, alpha-santalol treatment increased expressions of wild-type p53
      in UACC-62 cells. Knockdown of p21 in A431 cells, knockdown of p21 and p53 in
      UACC-62 cells did not affect cell cycle arrest caused by alpha-santalol.
      Furthermore, alpha-santalol caused depolymerization of microtubules similar to
      vinblastine in UACC-62 cells. CONCLUSIONS: This study for the first time
      identifies effects of alpha-santalol in G2/M phase arrest and describes detailed
      mechanisms of G2/M phase arrest by this agent, which might be contributing to its
      overall cancer preventive efficacy in various mouse skin cancer models.

PMID- 20682068
TI  - Tetrathiomolybdate inhibits head and neck cancer metastasis by decreasing tumor
      cell motility, invasiveness and by promoting tumor cell anoikis.
AB  - BACKGROUND: The metastatic spread of solid tumors is directly or indirectly
      responsible for most cancer-related deaths. Tumor metastasis is very complex and
      this process requires a tumor cell to acquire enhanced motility, invasiveness and
      anoikis resistance to successfully establish a tumor at a distal site. Metastatic
      potential of tumor cells is directly correlated with the expression levels of
      several angiogenic cytokines. Copper is a mandatory cofactor for the function of
      many of these angiogenic mediators as well as other proteins that play an
      important role in tumor cell motility and invasiveness. We have previously shown
      that tetrathiomolybdate (TM) is a potent chelator of copper and it mediates its
      anti-tumor effects by suppressing tumor angiogenesis. However, very little is
      known about the effect of TM on tumor cell function and tumor metastasis. In this
      study, we explored the mechanisms underlying TM-mediated inhibition of tumor
      metastasis. RESULTS: We used two in vivo models to examine the effects of TM on
      tumor metastasis. Animals treated with TM showed a significant decrease in lung
      metastasis in both in vivo models as compared to the control group. In addition,
      tumor cells from the lungs of TM treated animals developed significantly smaller
      colonies and these colonies had significantly fewer tumor cells. TM treatment
      significantly decreased tumor cell motility and invasiveness by inhibiting lysyl
      oxidase (LOX) activity, FAK activation and MMP2 levels. Furthermore, TM treatment
      significantly enhanced tumor cell anoikis by activating p38 MAPK cell death
      pathway and by downregulating XIAP survival protein expression. CONCLUSIONS:
      Taken together, these results suggest that TM is a potent suppressor of head and
      neck tumor metastasis by modulating key regulators of tumor cell motility,
      invasiveness and anoikis resistance.

PMID- 20682069
TI  - Successful thrombolysis of a thrombosed prosthetic mitral valve using a synthetic
      tissue plasminogen activator: a case report.
AB  - INTRODUCTION: Prosthetic valve thrombosis is a rare but life-threatening
      condition that requires careful evaluation and prompt treatment. While surgical
      intervention remains the gold standard, thrombolytic therapy is now emerging as a
      potential substitute. Various thrombolytic treatments including streptokinase,
      urokinase and recombinant tissue plasminogen activators have been reported with
      variable success rates. However, the data on the use of tenecteplase (a synthetic
      tissue plasminogen activator) is limited. CASE PRESENTATION: A 44-year-old Middle
      Eastern man with a previously implanted prosthetic mitral valve presented with
      exertional dyspnea and orthopnea. Investigations revealed a thrombosed prosthetic
      mitral valve. Successful thrombolysis was achieved using tenecteplase which lead
      to the complete restoration of valve function with no risk to the patient.
      CONCLUSION: Prosthetic valve thrombosis is a rare but life threatening condition,
      the diagnosis of which requires a high index of suspicion. Tenecteplase can be
      used successfully in the management of such cases. It has proved to be useful
      with no extra risk to the patient.

PMID- 20682070
TI  - Visualization and phenotyping of proinflammatory antigen-specific T cells during
      collagen-induced arthritis in a mouse with a fixed collagen type II-specific
      transgenic T-cell receptor beta-chain.
AB  - INTRODUCTION: The Vbeta12-transgenic mouse was previously generated to
      investigate the role of antigen-specific T cells in collagen-induced arthritis
      (CIA), an animal model for rheumatoid arthritis. This mouse expresses a
      transgenic collagen type II (CII)-specific T-cell receptor (TCR) beta-chain and
      consequently displays an increased immunity to CII and increased susceptibility
      to CIA. However, while the transgenic Vbeta12 chain recombines with endogenous
      alpha-chains, the frequency and distribution of CII-specific T cells in the
      Vbeta12-transgenic mouse has not been determined. The aim of the present report
      was to establish a system enabling identification of CII-specific T cells in the
      Vbeta12-transgenic mouse in order to determine to what extent the transgenic
      expression of the CII-specific beta-chain would skew the response towards the
      immunodominant galactosylated T-cell epitope and to use this system to monitor
      these cells throughout development of CIA. METHODS: We have generated and
      thoroughly characterized a clonotypic antibody, which recognizes a TCR specific
      for the galactosylated CII(260-270) peptide in the Vbeta12-transgenic mouse.
      Hereby, CII-specific T cells could be quantified and followed throughout
      development of CIA, and their phenotype was determined by combinatorial analysis
      with the early activation marker CD154 (CD40L) and production of cytokines.
      RESULTS: The Vbeta12-transgenic mouse expresses several related but distinct T
      cell clones specific for the galactosylated CII peptide. The clonotypic antibody
      could specifically recognize the majority (80%) of these. Clonotypic T cells
      occurred at low levels in the naive mouse, but rapidly expanded to around 4% of
      the CD4+ T cells, whereupon the frequency declined with developing disease.
      Analysis of the cytokine profile revealed an early Th1-biased response in the
      draining lymph nodes that would shift to also include Th17 around the onset of
      arthritis. Data showed that Th1 and Th17 constitute a minority among the CII
      specific population, however, indicating that additional subpopulations of
      antigen-specific T cells regulate the development of CIA. CONCLUSIONS: The
      established system enables the detection and detailed phenotyping of T cells
      specific for the galactosylated CII peptide and constitutes a powerful tool for
      analysis of the importance of these cells and their effector functions throughout
      the different phases of arthritis.

PMID- 20682071
TI  - Daily physical activity and its contribution to the health-related quality of
      life of ambulatory individuals with chronic stroke.
AB  - BACKGROUND: Participation in daily physical activity (PA) post-stroke has not
      previously been investigated as a possible explanatory variable of health-related
      quality of life (HRQL). The aims were 1) to determine the contribution of daily
      PA to the HRQL of individuals with chronic stroke and 2) to assess the
      relationship between the functional ability of these individuals to the amount of
      daily PA. METHODS: The amount of daily PA of forty adults with chronic stroke
      (mean age 66.5 +/- 9.6 years) was monitored using two measures. Accelerometers
      (Actical) were worn on the hip for three consecutive days in conjunction with a
      self-report questionnaire [the PA Scale for Individuals with Physical
      Disabilities (PASIPD)]. The daily physical activity was measured as the mean
      total accelerometer activity counts/day and the PASIPD scores as the metabolic
      equivalent (MET) hr/day. HRQL was assessed by the Physical and Mental composite
      scores of the Medical Outcomes Study Short-Form 36 (SF-36) in addition to the
      functional ability of the participants. Correlation and regression analyses were
      performed. RESULTS: After controlling for the severity of the motor impairment,
      the amount of daily PA, as assessed by the PASIPD and accelerometers, was found
      to independently contribute to 10-12% of the variance of the Physical Composite
      Score of the SF-36. No significant relationship was found between PA and the
      Mental Composite Score of the SF-36.The functional ability of the participants
      was found to be correlated to the amount of daily PA (r = 0.33 - 0.67, p < 0.01).
      CONCLUSION: The results suggest that daily PA is associated with better HRQL (as
      assessed by the Physical composite score of the SF-36) for people living with
      stroke. Daily PA should be encouraged to potentially increase HRQL.
      Accelerometers in conjunction with a self-report questionnaire may provide
      important measures of PA which can be monitored and modified, and potentially
      influence HRQL.

PMID- 20682072
TI  - Effects of capsinoid ingestion on energy expenditure and lipid oxidation at rest
      and during exercise.
AB  - BACKGROUND: The thermogenic and metabolic properties of capsinoids appear to
      mimic those of the more pungent sister compound capsaicin. However, few data
      exist on how capsinoid ingestion affects energy expenditure in humans and no data
      exist on its interaction with exercise. We aimed to determine how ingestion of
      capsinoids affected energy expenditure, lipid oxidation and blood metabolites at
      rest and during moderate intensity exercise. METHODS: Twelve healthy young men
      (age = 24.3 +/- 3 yr, BMI = 25.5 +/- 1.7 kg.m-2) were studied on two occasions in
      a double-blind design following ingestion of either placebo or 10 mg of purified
      capsinoids at rest, after 90 min of cycling at 55% VO2 peak, and for 30 min into
      recovery. Subjects ingested the capsules 30 min prior to exercise. RESULTS: At
      rest, following ingestion of capsinoids, we observed increases in VO2 and plasma
      norepinephrine levels, and decreases in concentrations of serum free fatty acids,
      plasma glycerol and the respiratory exchange ratio (all P < 0.05). At exercise
      onset, we observed a blunted accumulation of blood lactate with capsinoid
      ingestion vs. placebo (P < 0.05). There were no other significant differences
      between the conditions during or post-exercise. CONCLUSION: The ingestion of 10
      mg of capsinoids increased adrenergic activity, energy expenditure, and resulted
      in a shift in substrate utilization toward lipid at rest but had little effect
      during exercise or recovery. The changes we observed confirm previous data on the
      thermogenic and metabolic effects of capsinoids at rest and further promote its
      potential role as an adjunct weight loss aid, in addition to diet and exercise.

PMID- 20682073
TI  - Are mimics monophyletic? The necessity of phylogenetic hypothesis tests in
      character evolution.
AB  - BACKGROUND: The processes governing the origin and maintenance of mimetic
      phenotypes can only be understood in a phylogenetic framework. Phylogenetic
      estimates of evolutionary relationships can provide a context for analyses of
      character evolution; however, when phylogenetic estimates conflict, rigorous
      analyses of alternative evolutionary histories are necessary to determine the
      likelihood of a specific history giving rise to the observed pattern of
      diversity. The polyphenic butterfly Limenitis arthemis provides a case in point.
      This species is comprised of three lineages, two of which are mimetic and one of
      which is non-mimetic. Conflicting estimates of the relationships among these
      three lineages requires direct evaluation of the alternative hypotheses of
      mimicry evolution. RESULTS: Using a coalescent framework, we found support for a
      sister-taxon relationship between the non-mimetic L. a. arthemis and the mimetic
      L. a. astyanax, congruent with the previous hypothesis that the non-mimetic form
      of L. a. arthemis was derived from a mimetic ancestor. We found no support for a
      mimetic clade (L. a. astyanax + L. a. arizonensis) despite analyzing numerous
      models of population structure. CONCLUSIONS: These results provide the foundation
      for future studies of mimicry, which should integrate phylogenetic and
      developmental analyses of wing pattern formation. We propose future analyses of
      character evolution accommodate conflicting phylogenetic estimates by explicitly
      testing alternative evolutionary hypotheses.

PMID- 20682074
TI  - Testing the recent theories for the origin of the hermaphrodite flower by
      comparison of the transcriptomes of gymnosperms and angiosperms.
AB  - BACKGROUND: Different theories for the origin of the angiosperm hermaphrodite
      flower make different predictions concerning the overlap between the genes
      expressed in the male and female cones of gymnosperms and the genes expressed in
      the hermaphrodite flower of angiosperms. The Mostly Male (MM) theory predicts
      that, of genes expressed primarily in male versus female gymnosperm cones, an
      excess of male orthologs will be expressed in flowers, excluding ovules, while
      Out Of Male (OOM) and Out Of Female (OOF) theories predict no such excess.
      RESULTS: In this paper, we tested these predictions by comparing the
      transcriptomes of three gymnosperms (Ginkgo biloba, Welwitschia mirabilis and
      Zamia fisheri) and two angiosperms (Arabidopsis thaliana and Oryza sativa), using
      EST data. We found that the proportion of orthologous genes expressed in the
      reproductive organs of the gymnosperms and in the angiosperms flower is
      significantly higher than the proportion of orthologous genes expressed in the
      reproductive organs of the gymnosperms and in the angiosperms vegetative tissues,
      which shows that the approach is correct. However, we detected no significant
      differences between the proportion of gymnosperm orthologous genes expressed in
      the male cone and in the angiosperms flower and the proportion of gymnosperm
      orthologous genes expressed in the female cone and in the angiosperms flower.
      CONCLUSIONS: These results do not support the MM theory prediction of an excess
      of male gymnosperm genes expressed in the hermaphrodite flower of the angiosperms
      and seem to support the OOM/OOF theories. However, other explanations can be
      given for the 1:1 ratio that we found. More abundant and more specific (namely
      carpel and ovule) expression data should be produced in order to further test
      these theories.

PMID- 20682075
TI  - Extracting the abstraction pyramid from complex networks.
AB  - BACKGROUND: At present, the organization of system modules is typically limited
      to either a multilevel hierarchy that describes the "vertical" relationships
      between modules at different levels (e.g., module A at level two is included in
      module B at level one), or a single-level graph that represents the "horizontal"
      relationships among modules (e.g., genetic interactions between module A and
      module B). Both types of organizations fail to provide a broader and deeper view
      of the complex systems that arise from an integration of vertical and horizontal
      relationships. RESULTS: We propose a complex network analysis tool, Pyramabs,
      which was developed to integrate vertical and horizontal relationships and
      extract information at various granularities to create a pyramid from a complex
      system of interacting objects. The pyramid depicts the nested structure implied
      in a complex system, and shows the vertical relationships between abstract
      networks at different levels. In addition, at each level the abstract network of
      modules, which are connected by weighted links, represents the modules'
      horizontal relationships. We first tested Pyramabs on hierarchical random
      networks to verify its ability to find the module organization pre-embedded in
      the networks. We later tested it on a protein-protein interaction (PPI) network
      and a metabolic network. According to Gene Ontology (GO) and the Kyoto
      Encyclopedia of Genes and Genomes (KEGG), the vertical relationships identified
      from the PPI and metabolic pathways correctly characterized the inclusion (i.e.,
      part-of) relationship, and the horizontal relationships provided a good
      indication of the functional closeness between modules. Our experiments with
      Pyramabs demonstrated its ability to perform knowledge mining in complex systems.
      CONCLUSIONS: Networks are a flexible and convenient method of representing
      interactions in a complex system, and an increasing amount of information in real
      world situations is described by complex networks. We considered the analysis of
      a complex network as an iterative process for extracting meaningful information
      at multiple granularities from a system of interacting objects. The quality of
      the interpretation of the networks depends on the completeness and expressiveness
      of the extracted knowledge representations. Pyramabs was designed to interpret a
      complex network through a disclosure of a pyramid of abstractions. The
      abstraction pyramid is a new knowledge representation that combines vertical and
      horizontal viewpoints at different degrees of abstraction. Interpretations in
      this form are more accurate and more meaningful than multilevel dendrograms or
      single-level graphs. Pyramabs can be accessed at
      http://140.113.166.165/pyramabs.php/.

PMID- 20682076
TI  - Deep venous thrombosis after office vasectomy: a case report.
AB  - INTRODUCTION: Postoperative pulmonary embolism is considered a complication of
      major surgery. However, thromboembolism can also occur following minor
      procedures. We report a case of a major embolic event following a straightforward
      office vasectomy. CASE PRESENTATION: A healthy 35-year-old Asian man underwent an
      uncomplicated office vasectomy. Soon after, he noticed vague chest pain and
      dyspnea. Lower extremity Doppler ultrasound revealed acute venous thrombosis. A
      computer-assisted tomography angiogram revealed extensive bilateral pulmonary
      emboli. Extensive laboratory work-up failed to identify thrombophilia. He has not
      had any recurrences in the eight years since the initial presentation.
      CONCLUSION: This case highlights that major embolic events can follow minor
      office procedures. Patients with suggestive findings should be investigated
      aggressively.

PMID- 20682077
TI  - The impact of universal National Health Insurance on population health: the
      experience of Taiwan.
AB  - BACKGROUND: Taiwan established a system of universal National Health Insurance
      (NHI) in March, 1995. Today, the NHI covers more than 98% of Taiwan's population
      and enrollees enjoy almost free access to healthcare with small co-payment by
      most clinics and hospitals. Yet while this expansion of coverage will almost
      inevitably have improved access to health care, however, it cannot be assumed
      that it will necessarily have improved the health of the population. The aim of
      this study was to determine whether the introduction of National Health Insurance
      (NHI) in Taiwan in 1995 was associated with a change in deaths from causes
      amenable to health care. METHODS: Identification of discontinuities in trends in
      mortality considered amenable to health care and all other conditions (non
      amenable mortality) using joinpoint regression analysis from 1981 to 2005.
      RESULTS: Deaths from amenable causes declined between 1981 and 1993 but slowed
      between 1993 and 1996. Once NHI was implemented, the decline accelerated
      significantly, falling at 5.83% per year between 1996 and 1999. In contrast,
      there was little change in non-amenable causes (0.64% per year between 1981 and
      1999). The effect of NHI was highest among the young and old, and lowest among
      those of working age, consistent with changes in the pattern of coverage. NHI was
      associated with substantial reductions in deaths from circulatory disorders and,
      for men, infections, whilst an earlier upward trend in female cancer deaths was
      reversed. CONCLUSIONS: NHI was associated in a reduction in deaths considered
      amenable to health care; particularly among those age groups least likely to have
      been insured previously.

PMID- 20682078
TI  - Up-regulation of p21 and TNF-alpha is mediated in lycorine-induced death of HL-60
      cells.
AB  - BACKGROUND: Leukemia is one of the most life-threatening cancers today, and acute
      promyelogenous leukemia (APL) is a common type of leukemia. Many natural
      compounds have already been found to exhibit significant anti-tumor effects.
      Lycorine, a natural alkaloid extracted from Amaryllidaceae, exhibited anti
      leukemia effects in vitro and in vivo. The survival rate of HL-60 cells exposed
      to lycorine was decreased, cell growth was slowed down, and cell regeneration
      potential was inhibited. HL-60 cells exhibited typical apoptotic characteristic.
      Lycorine can suppress leukemia growth and reduce cell survival and inducing
      apoptosis of tumor cells. The purpose of this work is to elucidate the mechanism
      by which lycorine induces APL cells. RESULTS: When HL-60 cells were treated with
      different concentration of lycorine, the expression of p21 and TNF-alpha was up
      regulated in a concentration-dependent manner as shown by real-time quantitative
      reverse transcriptase-polymerase chain reaction and Western blotting. Lycorine
      also down-regulated p21-related gene expression, including Cdc2, Cyclin B, Cdk2
      and Cyclin E, promoted Bid truncation, decreased IkappaB phosphorylation and
      blocked NF-kappaB nuclear import. Cytochrome c was released from mitochondria as
      observed with confocal laser microscopy. CONCLUSIONS: The TNF-alpha signal
      transduction pathway and p21-mediated cell-cycle inhibition were involved in the
      apoptosis of HL-60 cells induced by lycorine. These results contribute to the
      development of new lycorine-based anti-leukemia drugs.

PMID- 20682079
TI  - Enterovirus type 71 2A protease functions as a transcriptional activator in
      yeast.
AB  - Enterovirus type 71 (EV71) 2A protease exhibited strong transcriptional activity
      in yeast cells. The transcriptional activity of 2A protease was independent of
      its protease activity. EV71 2A protease retained its transcriptional activity
      after truncation of 40 amino acids at the N-terminus but lost this activity after
      truncation of 60 amino acids at the N-terminus or deletion of 20 amino acids at
      the C-terminus. Thus, the acidic domain at the C-terminus of this protein is
      essential for its transcriptional activity. Indeed, deletion of amino acids from
      146 to 149 (EAME) in this acidic domain lost the transcriptional activity of EV71
      2A protein though still retained its protease activity. EV71 2A protease was
      detected both in the cytoplasm and nucleus using confocal microscopy analysis.
      Coxsackie virus B3 2A protease also exhibited transcriptional activity in yeast
      cells. As expected, an acidic domain in the C-terminus of Coxsackie virus B3 2A
      protease was also identified. Truncation of this acidic domain resulted in the
      loss of transcriptional activity. Interestingly, this acidic region of poliovirus
      2A protease is critical for viral RNA replication. The transcriptional activity
      of the EV71 or Coxsackie virus B3 2A protease should play a role in viral
      replication and/or pathogenesis.

PMID- 20682081
TI  - A prevalence survey of every-day activities in pregnancy.
AB  - BACKGROUND: Research into the effects of common activities during pregnancy is
      sparse and often contradictory. To examine whether common activities are an acute
      trigger of pregnancy complications the prevalence of these activities are
      necessary to determine sample size estimates. The aim of this study is to
      ascertain the prevalence of selected activities in any seven day period during
      pregnancy. METHODS: The study was conducted in the antenatal clinic of a teaching
      hospital with tertiary obstetric and neonatal care in Sydney, Australia between
      August 2008 and April 2009. Women who were at least 20 weeks pregnant and able to
      read English completed a questionnaire to assess whether they had performed a
      list of activities in the seven days prior to survey completion. Results were
      analysed using frequency tabulations, contingency table analyses and chi square
      tests. RESULTS: A total of 766 surveys were completed, 29 surveys were excluded
      as the women completing them were less than 20 weeks pregnant, while 161 women
      completed the survey more than once. Ninety seven per cent of women completed the
      survey when approached for the first time, while 87% completed the survey when
      approached a subsequent time. In the week prior to completing the survey 82.6% of
      women had consumed a caffeinated beverage, 42.1% had had sexual intercourse,
      32.7% had lifted something over 12 kilograms, 21.4% had consumed alcohol and 6.4%
      had performed vigorous exercise. The weekly prevalence of heavy lifting was
      higher for multiparous women compared to nulliparous women. CONCLUSIONS: The
      results of this study can be used to inform future research into activities as
      acute triggers of pregnancy complications.

PMID- 20682080
TI  - Characterisation of microRNAs from apple (Malus domestica 'Royal Gala') vascular
      tissue and phloem sap.
AB  - BACKGROUND: Plant microRNAs (miRNAs) are a class of small, non-coding RNAs that
      play an important role in development and environmental responses. Hundreds of
      plant miRNAs have been identified to date, mainly from the model species for
      which there are available genome sequences. The current challenge is to
      characterise miRNAs from plant species with agricultural and horticultural
      importance, to aid our understanding of important regulatory mechanisms in crop
      species and enable improvement of crops and rootstocks. RESULTS: Based on the
      knowledge that many miRNAs occur in large gene families and are highly conserved
      among distantly related species, we analysed expression of twenty-one miRNA
      sequences in different tissues of apple (Malus x domestica 'Royal Gala'). We
      identified eighteen sequences that are expressed in at least one of the tissues
      tested. Some, but not all, miRNAs expressed in apple tissues including the phloem
      tissue were also detected in the phloem sap sample derived from the stylets of
      woolly apple aphids. Most of the miRNAs detected in apple phloem sap were also
      abundant in the phloem sap of herbaceous species. Potential targets for apple
      miRNAs were identified that encode putative proteins shown to be targets of
      corresponding miRNAs in a number of plant species. Expression patterns of
      potential targets were analysed and correlated with expression of corresponding
      miRNAs. CONCLUSIONS: This study validated tissue-specific expression of apple
      miRNAs that target genes responsible for plant growth, development, and stress
      response. A subset of characterised miRNAs was also present in the apple phloem
      translocation stream. A comparative analysis of phloem miRNAs in herbaceous
      species and woody perennials will aid our understanding of non-cell autonomous
      roles of miRNAs in plants.

PMID- 20682082
TI  - Cetirizine a histamine H1 receptor antagonist improves viral myocarditis.
AB  - BACKGROUND: We showed that mast cells played a critical role in the progression
      of heart failure induced by pressure overload and viral myocarditis in mice. In
      this study, we investigated the effect of cetirizine, a selective H1 receptor
      antagonist, on experimental viral myocarditis induced by encephalomyocarditis
      (EMC) virus. METHODS: Four-week-old inbred male DBA/2 mice were inoculated
      intraperitoneally with 10 plaque-forming units (pfu) of the EMC virus. Cetirizine
      was administered orally at a dose of 1 or 10 mg/kg per day for the survival
      study, and 1 mg/kg for the histologic and gene expression studies, beginning on
      the day of viral inoculation. RESULTS: Cetirizine improved survival dose
      dependently. Heart weight to body weight ratio was significantly decreased in
      mice treated with cetirizine. The area of myocardial necrosis was significantly
      smaller in the hearts of mice treated with cetirizine compared with controls.
      Gene expressions of tumor necrosis factor, interleukin 6, and metalloproteinase 2
      were significantly suppressed in the hearts of mice treated with cetirizine.
      CONCLUSION: These results suggest that cetirizine exerts its beneficial effects
      on viral myocarditis by suppressing expression of pro-inflammatory cytokines,
      genes related to cardiac remodeling in the hearts of mice.

PMID- 20682083
TI  - Does dissemination extend beyond publication: a survey of a cross section of
      public funded research in the UK.
AB  - BACKGROUND: In the UK, most funding bodies now expect a commitment or effort on
      the part of grant holders to disseminate the findings of their research. The
      emphasis is on ensuring that publicly funded research is made available, can be
      used to support decision making, and ultimately improve the quality and delivery
      of healthcare provided. In this study, we aimed to describe the dissemination
      practices and impacts of applied and public health researchers working across the
      UK. METHODS: We conducted a survey of 485 UK-based principal investigators of
      publicly funded applied and public health research. Participants were contacted
      by email and invited to complete an online questionnaire via an embedded URL.
      Gift vouchers were given to all participants who completed the questionnaire.
      Four reminder emails were sent out to non-respondents at one, two, three, and
      four weeks; a fifth postal reminder was also undertaken. RESULTS: A total of
      243/485 (50%) questionnaires were returned (232 completed, 11 declining to
      participate). Most researchers recognise the importance of and appear committed
      to research dissemination. However, most dissemination activity beyond the
      publishing of academic papers appears to be undertaken an ad hoc fashion. There
      is some evidence that access to dissemination advice and support may facilitate
      more policy interactions; though access to such resources is lacking at an
      institutional level, and advice from funders can be variable. Although a minority
      of respondents routinely record details about the impact of their research, when
      asked about impact in relation to specific research projects most were able to
      provide simple narrative descriptions. CONCLUSIONS: Researchers recognise the
      importance of and appear committed to disseminating the findings of their work.
      Although researchers are focussed on academic publication, a range of
      dissemination activities are being applied albeit in an ad hoc fashion. However,
      what constitutes effective dissemination (in terms of impact and return on
      investment) remains unclear. Researchers need greater and clearer guidance on how
      best to plan, resource, and facilitate their dissemination activities.

PMID- 20682084
TI  - The role of animal models in advancing amyloid-beta immunotherapy to the clinic.
AB  - The amyloid-beta (Abeta) hypothesis of Alzheimer's disease (AD) causality is now
      well into its third decade and is finally entering a phase of rigorous clinical
      testing in numerous late stage clinical trials. The use of Abeta-based animal
      models of AD has been essential to the discovery and/or preclinical validation of
      many of these therapeutic approaches. While several neuropathologically based
      results from preclinical studies have translated nicely into AD patients, the
      full clinical value of Abeta-directed therapies awaits results from trials now in
      progress.

PMID- 20682085
TI  - Optimizing protease production from an isolate of the nematophagous fungus
      Duddingtonia flagrans using response surface methodology and its larvicidal
      activity on horse cyathostomins.
AB  - Protease production from Duddingtonia flagrans (isolate AC001) was optimized and
      the larvicidal activity of the enzymatic extract was evaluated on infective horse
      cyathostomin larvae (L3). Duddingtonia flagrans was grown in liquid medium with
      eight different variables: glucose, casein, bibasic potassium phosphate (K2HPO4),
      magnesium sulphate (MgSO4), zinc sulphate (ZnSO4), ferrous sulphate (FeSO4),
      copper sulphate (CuSO4) and temperature. The Plackett-Burman analysis showed a
      significant influence of MgSO4, CuSO4 and casein (P < 0.05) on protease
      production by D. flagrans in liquid medium. Central composite design indicated
      that the highest proteolytic activity was 39.56 U/ml as a function of the
      concentrations of casein (18.409 g/l), MgSO4 (0.10 g/l) and CuSO4 (0.50 mg/l). A
      significant difference (P < 0.01) was found for the larval number between the
      treated and control groups at the end of the experiment. A reduction of 95.46% in
      the number of free-living larvae was found in the treated group compared with the
      control. The results of this study suggest that protease production by D.
      flagrans (AC001) in liquid medium was optimized by MgSO4, CuSO4 and casein,
      showing that the optimized enzymatic extract exerted larvicidal activity on
      cyathostomins and therefore may contribute to large-scale industrial production.

PMID- 20682086
TI  - Postconcussive symptoms after blast and nonblast-related mild traumatic brain
      injuries in Afghanistan and Iraq war veterans.
AB  - Blast injury is common in current warfare, but little is known about the effects
      of blast-related mild traumatic brain injury (mTBI). Profile analyses were
      conducted investigating differences in self-reported postconcussive (PC) symptoms
      in 339 veteran outpatients with mTBI histories reporting current symptoms based
      on mechanism of injury (blast only, nonblast only, or both blast and nonblast),
      number of blast injuries, and distance from the blast. Veterans with any blast
      related mTBI history were younger and reported higher posttraumatic stress
      symptoms than veterans with nonblast-related mTBI histories, with a marginally
      significant difference in posttraumatic stress symptom report between veterans
      reporting blast-related mTBI only and those reporting nonblast-related mTBI. The
      groups did not differ in terms of PC symptom severity or PC symptom cluster
      profiles. Among veterans with blast-related mTBI histories, PC symptom report did
      not vary by number of blast-related mTBIs or proximity to blast. Overall,
      posttraumatic stress symptoms accounted for a substantial portion of variance in
      PC symptom report. In veteran outpatients with remote mTBI histories who have
      enduring symptom complaints related to the mTBI, mechanism of injury did not
      clearly contribute to differential PC symptom severity or PC symptom cluster
      profile. Proximal rather than distal factors may be important intervention
      targets in returning symptomatic veterans with mTBI histories.

PMID- 20682087
TI  - Executive dysfunction in children with neurofibromatosis type 1: a study of
      action planning.
AB  - In this study, we tested the hypothesis that action planning is impaired in
      children with neurofibromatosis type 1 (NF1). Thirty-six children with NF1 were
      pair-matched to 36 healthy controls (HC) on age (range, 7-12 years), sex, and
      parental education level, and both groups were administered three action-planning
      tasks. To examine the relation of task performance to attention deficit
      hyperactivity disorder (ADHD), the NF1 group was divided into subsets of children
      who met or did not meet criteria for ADHD. Children with NF1 performed less well
      than HC on all planning tasks, and differences remained when controlling for IQ
      or a measure of visuospatial skill. Both the NF1 with ADHD subset and NF1 without
      ADHD subset performed more poorly than HC on two of the tasks, whereas only the
      NF1 with ADHD subset performed worse than HC on the third planning task. The
      results underscore the importance of evaluating executive function in children
      with NF1 and suggest that deficits in this domain may be only partially related
      to ADHD. Planning deficits in children with NF1 may be part of their cognitive
      phenotype. Identifying these deficits is relevant in determining factors
      contributing to learning problems and in developing appropriate interventions.

PMID- 20682088
TI  - Early detection of Alzheimer's disease with a total score of the German CERAD.
AB  - The goal of the present study was to evaluate the diagnostic discriminability of
      three different global scores for the German version of the Consortium to
      Establish a Registry on Alzheimer's Disease-Neuropsychological Assessment Battery
      (CERAD-NAB). The CERAD-NAB was administered to 1100 healthy control participants
      [NC; Mini-Mental State Examination (MMSE) mean = 28.9] and 352 patients with very
      mild Alzheimer's disease (AD; MMSE mean = 26.1) at baseline and subsets of
      participants at follow-up an average of 2.4 (NC) and 1.2 (AD) years later. We
      calculated the following global scores: Chandler et al.'s (2005) score (summed
      raw scores), logistic regression on principal components analysis scores (PCA
      LR), and logistic regression on demographically corrected CERAD-NAB variables
      (LR). Correct classification rates (CCR) were compared with areas under the
      receiver operating characteristics curves (AUC). The CCR of the LR score (AUC =
      .976) exceeded that of the PCA-LR, while the PCA-LR (AUC = .968) and Chandler
      (AUC = .968) scores performed comparably. Retest data improved the CCR of the PCA
      LR and Chandler (trend) scores. Thus, for the German CERAD-NAB, Chandler et al.'s
      total score provided an effective global measure of cognitive functioning,
      whereby the inclusion of retest data tended to improve correct classification of
      individual cases.

PMID- 20682089
TI  - Plant-based strategies towards minimising 'livestock's long shadow'.
AB  - Ruminant farming is an important component of the human food chain. Ruminants can
      use offtake from land unsuitable for cereal crop cultivation via interaction with
      the diverse microbial population in their rumens. The rumen is a continuous flow
      fermenter for the digestion of ligno-cellulose, with microbial protein and
      fermentation end-products incorporated by the animal directly or during post
      ruminal digestion. However, ruminal fermentation is inefficient in capturing the
      nutrient resource presented, resulting in environmental pollution and generation
      of greenhouse gases. Methane is generated as a consequence of ruminal
      fermentation and poor retention of ingested forage nitrogen causes nitrogenous
      pollution of water and land and contributes to the generation of nitrous oxide.
      One possible cause is the imbalanced provision of dietary substrates to the rumen
      micro-organisms. Deamination of amino acids by ammonia-producing bacteria
      liberates ammonia which can be assimilated by the rumen bacteria and used for
      microbial protein synthesis. However, when carbohydrate is limiting, microbial
      growth is slow, meaning low demand for ammonia for microbial protein synthesis
      and excretion of the excess. Protein utilisation can therefore be improved by
      increasing the availability of readily fermentable sugars in forage or by making
      protein unavailable for proteolysis through complexing with plant secondary
      products. Alternatively, realisation that grazing cattle ingest living cells has
      led to the discovery that plant cells undergo endogenous, stress-mediated protein
      degradation due to the exposure to rumen conditions. This presents the
      opportunity to decrease the environmental impact of livestock farming by using
      decreased proteolysis as a selection tool for the development of improved pasture
      grass varieties.

PMID- 20682091
TI  - Letter to the editor.

PMID- 20682092
TI  - Letter to the journal.

PMID- 20682094
TI  - The WFNRS. Index Neuroradiologicum.

PMID- 20682090
TI  - Insight into helicase mechanism and function revealed through single-molecule
      approaches.
AB  - Helicases are a class of nucleic acid (NA) motors that catalyze NTP-dependent
      unwinding of NA duplexes into single strands, a reaction essential to all areas
      of NA metabolism. In the last decade, single-molecule (sm) technology has proven
      to be highly useful in revealing mechanistic insight into helicase activity that
      is not always detectable via ensemble assays. A combination of methods based on
      fluorescence, optical and magnetic tweezers, and flow-induced DNA stretching has
      enabled the study of helicase conformational dynamics, force generation, step
      size, pausing, reversal and repetitive behaviors during translocation and
      unwinding by helicases working alone and as part of multiprotein complexes. The
      contributions of these sm investigations to our understanding of helicase
      mechanism and function will be discussed.

PMID- 20682093
TI  - Editorial. The concept of the natural history or spontaneous evolution of
      vascular.

PMID- 20682095
TI  - Anatomoclinical Aspects of Dural Arteriovenous Shunts in Children. Review of 29
      cases.
AB  - SUMMARY: We review 29 children (presenting between 1985-1996) with dural
      arteriovenous shunts. By analysing the anatomical features from axial and
      angiographic imaging and examining the clinical history and pathophysiological
      characteristics, we hypothesize that different diseases can be distinguished and
      divided into three groups: dural sinus malformation (DSM), infantile type of
      dural arteriovenous shunts (IDAVS) and adult type of dural arteriovenous shunts
      (ADAVS). It was helpful to classify these diseases when assessing the treatment
      options and long-term prognosis. Our group of 29 children comprised 19 DSM, 7
      IDAVS, 3 ADAVS. A slight male preponderance was noted in the DSM group. The range
      of symptoms encountered included mild cardiac failure and coagulopathies,
      macrocrania, developmental delay, mental retardation, seizures and focal
      neurological deficits (in the neonates and early infancy age group) with or
      without haemorrhagic venous infarctions secondary to venous outlet restriction.
      We found all types of lesion in the neonatal age group, but in general the
      different types of lesion correspond to the paediatric subgroups with DSM
      occurring in the neonatal age group, IDAVS in infancy and ADAVS in children. DSMs
      are revealed in the first few months of live and the prognosis is good if the
      torcular is not involved. Two types can be seen: 1) DSM involving the posterior
      sinus with or without the confluens sinusum, with giant dural lakes and slow flow
      mural AV shunting. Spontaneous thrombosis may further restrict cerebral venous
      drainage and subsequently lead to intraparenchymatous haemorrhagic infarction. 2)
      DSM involving the jugular bulb with otherwise normal sinuses but associated with
      a high flow sigmoi'd sinus AVF. The prognosis is excellent with embolisation
      treament. IDAVS are high flow and low pressure. The sinuses are large and patent
      with no lakes. Clinical onset is seen in the first few years of life and the
      shunts are initially well tolerated. Progressive symptoms (symptoms of raised ICP
      and venous ischaemia) develop at a later age and initially respond to partial
      embolisation. The long term prognosis is poor with neurological deterioration in
      early adulthood. ADAVS present in all age groups and almost all of them are
      located in the cavernous venous plexus. Post embolisation outcome is excellent.

PMID- 20682096
TI  - Prevention of Complications during Endovascular Surgery on the External Carotid
      Arteries, with Special Reference to Use of Nitropaste and the Lidocaine test.
AB  - SUMMARY:  PURPOSE: To examine all complications of endovascular procedures on the
      external carotid arteries and to ascertain how to reduce their number. METHODS:
      In 93 consecutive patients, 137 endovascular procedures on the external carotid
      arteries were performed during the last 6 years. RESULTS: We encountered no
      neurologic complications in these patients. In eight (9%) of the 93 patients who
      underwent lidocaine tests of the external carotid branches, nine transient
      cranial nerve palsies occured, seven of 67 vessels (10%) involving the middle
      meningeal artery and two of 18 vessels (11%) the ascending pharyngeal artery.
      However, they soon disappeared and successful embolisations were achieved.
      Vasospasm that prevented endovascular procedures occurred in only two cases of
      this series as a result of the application of isosorbide dinitrate. CONCLUSIONS:
      The lidocaine test effectively provoked cranial nerve palsies without false
      negatives. The complication rate of endovascular surgery will decrease as long as
      awareness of complications such as cranial nerve palsy is maintained.

PMID- 20682097
TI  - The guglielmi detachable coil in the treatment of arteriovenous fistulae.
AB  - SUMMARY: This report describes the use of the Guglielmi Detachable Coil (GDC)
      (Target Therapeutics, Fremont CA) in the treatment of cervicocerebral
      arteriovenous fistulae. From March, 1993 to May 1995 we used GDCs in an 1RB
      approved protocol as part of the endovascular treatment of 11 patients with
      arteriovenous fistulae of internal carotid, external carotid, or vertebral
      vessels. The patient population included four patients with dural arteriovenous
      fistulae, three patients with direct carotid cavernous fistulae, three patients
      with vein of Galen malformations, and one patient with a vertebral artery -
      vertebral vein fistula. In six of the 11 patients the AVF were completely
      occluded. Fistula occlusion occurred in two patients immediately, in three
      patients in a delayed fashion (three days to nine months) and in one patient the
      fistula was closed immediately, reopened spontaneously, and then reoccluded at a
      second procedure 17 months later. In five patients the fistula was incompletely
      occluded (20-95%). In all cases but one the coils were used in conjunction with
      another embolic agent. In this small series of patients we found that GDCs
      generally could be deposited predictably at the desired site, and that they could
      be observed prior to detachment to help ensure that the coil was in a secure
      position, decreasing the chances ofunintended passage into the venous outlet.
      Although they rarely proved thrombogenic enough to stop the fistula, GDCs can
      slow the flow in a fistula, allowing other, more thrombogenic embolic agents to
      be deposited with a decreased risk of distal embolisation. In conclusion, we
      found GDCs to be a useful tool in the treatment of AV fistulae. In combination
      with other embolic agents, this device can aid in the safe, effective closure of
      these lesions.

PMID- 20682098
TI  - Therapeutic infiltration of the facet joint in minor intervertebral disease.
AB  - SUMMARY: A CT-guided infiltration technique of the facet joints was employed on a
      group of 20 patients suffering from sciatica without any signs ofmorphostructural
      alteration of the facet joints, secondary to Minor Intervertebral Disease (MID).
      The typical flouroscopically guided intra-articular facet arthrography has been
      substituted by a CT-guided technique that privileges therapy rather than
      diagnosis. The study involved 20 patients between 29 and 57 years of age (average
      44.5), of both sexes (16 females and four males). The average time which elapsed
      from onset of symptomatology was 9.5 months. At seven days after the first
      treatment subjective results were considered excellent by 11 patients (55%), good
      by one (5%) and satisfactory by one (5%). Six out of20 patients (30%) failed to
      gain any relief of symptoms. Only one patient (5%) had a worsening of pain.
      Clinical evaluation by the physician at the same time showed a good result in 11
      patients (55%), satisfactory in two (10%). In six patients (30%) the
      symptomatology was unchanged. At 4 months the subjective results were excellent
      in three (15%), good in six (30%) and satisfactory in two (10%) . Nine (45%) had
      no positive results. The clinical examination was excellent in tWo (10%), good in
      seven (35%), satisfactory in two (10%) and without any relief of symptomatology
      in nine (45%). These results encourage the use of CT-guided infiltration that,
      together with the small amount of contrast medium injected into the joint space,
      make it a safe technique for patients, avoiding or reducing complications.

PMID- 20682099
TI  - The marginal sinus normal anatomy and involvement with arteriovenous fistulae.
AB  - SUMMARY:  RATIONALE AND OBJECTIVES: The marginal sinus is an infrequently
      recognized dural venous sinus at the rim of the foramen magnum. Recognition of
      this sinus and knowledge of its anatomy will enable the neurointerventionalist to
      treat dural arteriovenous fistulae (AVF) involving the marginal sinus. METHODS:
      We present a report of the signs, symptoms, angiographic appearance, and
      treatment results of two patients with marginal sinus dural AVF. In addition, we
      review the literature concerning the marginal sinus and describe the anatomy of
      this region. Angiograms depicting normal variants are presented to illustrate the
      various patterns that may be encountered when the marginal sinus participates in
      the venous drainage of the cranium. RESULTS: In two patients with dural
      arteriovenous fistulae (AVF) the marginal sinus was found to be the venous
      receptacle. The marginal sinuses are dural venous sinuses located at the lateral
      margins of the foramen magnum. Superiorly, the marginal sinus connects to the
      occipital sinus, a single or paired midline venous channel arising at the
      torcular Herophili or the medial transverse sinus. The marginal sinus typically
      drains into the sigmoid sinus, and may connect to the condylar veins, the
      superior aspect of the internal venous plexus, or the occipital plexus.
      Occasionally, the occipital-marginal sinus system represents the primary drainage
      pathway of the cranium, completely replacing the transverse sinus. In the two
      patients we treated with dural AVF in this location, simple transvenous packing
      of the sinus effectively cured the lesion. CONCLUSIONS: The marginal sinus is a
      dural venous sinus that can rarely be involved with a dural AVF. Recognition that
      a dural AVF involves the marginal sinus can facilitate safe, effective therapy.

PMID- 20682100
TI  - Dural arteriovenous shunts involving the sphenoparietal sinus: a case report.
AB  - SUMMARY: A 40-year-old male suffered transient global amnesia and was diagnosed
      as having a very rare location of dural arteriovenous shunt (dAVS) involving the
      right sphenoparietal sinus. The feeding pedicles of dAVS were not only arising
      from the right external carotid system, including the middle meningeal artery,
      but also the right internal carotid system including the ophthalmic artery. The
      dAVS drained into the right sphenoparietal sinus, right vein of Labbe, and right
      basal vein of Rosenthal through numerous dilated temporal cortical veins. The
      arteriovenous shunt itself was located at the dura around the right superior
      ophthalmic fissure and a large varix received direct shunting blood flow from the
      right sphenoparietal sinus. The dAVS was cured by drainer clipping following
      transarterial embolisations. A dAVS with cortical venous drainage is considered
      to have a higher risk of haemorrhage and venous infarction than the others and
      thus warrants treatment even if the clinical symptom is minimal. If the dAVS has
      a single drainer, it will be easily cured by way of drainer clipping.
      Preoperative embolisation makes clipping easier and safer. Intraoperative
      angiography is useful because preoperative angiography may not necessarily show
      the complete angioarchitecture around the lesion.

PMID- 20682101
TI  - A case of vertebrovertebral arteriovenous fistula presenting with subarachnoid
      haemorrhage. A case report.
AB  - SUMMARY: A rare paediatric case ofvertebrovertebral arteriovenous fistula
      presented with a subarachnoid haemorrhage. A 12 year-old boy, who fell on his
      back at school, presented with a one week history of headache, vomiting, and
      double vision. Computed tomography (CT) scan revealed subarachnoid haemorrhage.
      Magnetic resonance imaging (MRI) demonstrated a tortuous vessel on the anterior
      surface of the spinal cord. Selective angiography showed an arteriovenous fistula
      of the left vertebral artery at the level of Cl. The venous drainage of the
      fistula refluxed into the medullary vein at the level of C6-7, and drained
      upwards into the posterior fossa veins. An endovascular detachable balloon
      technique was employed and complete occlusion of the fistula was achieved.

PMID- 20682102
TI  - Review of the literature. Abstract from acta neurochirurgica and surgery for
      cerebral stroke (Japan).

PMID- 20682103
TI  - ESNR Meeting of the Executive Committee. Interventional Neuroradiology Committee.

PMID- 20682104
TI  - Editorial. Thirty years of interventional neuroradiology in europe.

PMID- 20682105
TI  - Spontaneous polymerisation of cyanoacrylate/lipiodol mixtures causing failed
      embolisation. Laboratory studies.
AB  - SUMMARY: In vitro experiments to investigate spontaneous polymerisation of n
      butyl-2-cyanoacrylate when mixed with non ionic oily contrast medium are
      reported. The results suggest an interaction between the mixture components which
      is unique to one particular batch of Lipiodol Ultrafluid and Histoacryl n butyl
      cyanoacrylate. The interaction cannot be reproduced with other batches of
      Lipiodol Ultrafluid nor with an alternative preparation of n-butyl-2
      cyanoacrylate. Implications for the use of the materials in neuro-interventional
      practice are discussed.

PMID- 20682106
TI  - Selective Intra-arterial Thrombolysis for Embolic Complications of Cerebral
      Endovascular Therapy.
AB  - SUMMARY: Cerebral thrombo-embolic complications seldom occur during intracranial
      endovascular therapeutic procedures. Yet, despite a systemic preventive regimen
      of pre-operative intravenous acetylsalicylic acid and effective systemic
      heparinisation, we encountered seven complications of this type over a period of
      five years, a 3.7 per thousand incidence (7/1858). Local intra-arterial
      thrombolysis performed immediately after the thrombo-embolic complication
      resulted in complete recanalization in five cases and partial recanalization in
      two. CT scans performed 24 hours after thrombolysis were normal in six of the
      seven patients. Only one female patient with partial recanalization showed a
      limited cortical infarct in the parietal distribution of the middle cerebral
      artery territory. In all seven cases recanalization of the occluded vessel
      resulted in a return to the baseline initial neurological status. This short
      series demonstrates the usefulness of emergent thrombolysis dealing with the
      thrombo-embolic complications of angiography or endovascular therapy. These
      results are in agreement with these experimental data showing that early
      recanalization can prevent macroscopically visible infarcts.

PMID- 20682107
TI  - Volume Determination of Intracranial Arteriovenous Malformations prior to
      Stereotactic Radiosurgical Treatment.
AB  - SUMMARY: Exact dose planning for stereotactic radiosurgery was enabled in
      connection with diagnostic angiography or at the end of an endovascular procedure
      by simply placing a stereotactic localizing box onto the head of the patient
      while acquiring PA and lateral angiographic views. The fiducials engraved on the
      localizing box enabled the appropriate images to be scaled to the stereotactic
      space. Regular dose planning was then performed after estimating the size of the
      patient's head. A prediction of the chances of obliteration and the risks of
      complication could then be made immediately after the en do vascular or
      diagnostic procedure, and further therapy could be selected much more
      confidently. This technique may also be used at centres without facilities for
      radiosurgical treatment if only the localizing box is available. The images may
      then be sent for evaluation to a unit with dose planning equipment. The technique
      is simple and involves little risk, significantly improving patient management.
      Digital subtraction angiography was used in this study. A correction algorithm
      was used to minimize the geometric distortion inherent to the digital technique.

PMID- 20682108
TI  - Intra-arterial Chemotherapy with Carboplatin (CBDCA) and Vepesid (VP16) in
      Primary Malignant Brain Tumours. Preliminary Findings.
AB  - SUMMARY: Twenty three patients (18 males) were followed from January 1993 to July
      1996 for primary central nervous system malignancy: glioblastoma multiforme (GM)
      (15 patients), anaplastic astrocytoma (AA) (8 patients). Ninety one cycles
      (average 4 cycles per patient) of intraarterial chemotherapy (IACH) were
      administered. The IACH included: Carboplatin (CBP) 250 mg/m2 and Vepesid (VPI6)
      150 mg/m2 infusion; both drugs in normal saline, 100 ml and 250 ml, were infused
      over 15 and 30 min respectively. IACH was repeated every two weeks four or six
      times according to response to chemotherapy. IACH was preceded by i.v.
      methylprednisolone 40mg and pure anti-emetic (5HT3 serotonin uptake inhibitors)
      and subcutaneous daily doses of G-CSF following IACH to prevent neutropenia. The
      whole treatment required a 24h hospital admission. The IACH was well-tolerated
      and toxicity (Miller's grade, WHO) included: two cases ofreversible pulmonary
      embolism (8.6%) three and ten days respectively after therapy (one patient had
      atrial fibrillation, two cases grade 2 vomiting, two grade 1 anaemia and three
      grade 3 thombocytopenia (13%). Response to therapy was evaluated in 21 out of 23
      patients, two having not yet received at least four IACH cycles: 4 PRO (3 GM, 1
      AA), 15 SD (10 GM, 5 AA) and 2 PR (AA). Seventeen patients responded to IACH (SD
      + RO) (74%), and the P Rs belonged to the AA group. Survival duration was from 16
      + to 108 weeks. IACH with CP and VP16 warrants further studies focussing on drug
      dose and schedule. A prospective randomized multicentric trial evaluating
      radiotherapy and systemic chemotherapy plus/minus IACH is currently underway.

PMID- 20682109
TI  - Post-Procedure CT Follow-up after Percutaneous Automated Lumbar Nucleotomy.
AB  - SUMMARY: In order to evaluate the incidence of soft tissue changes after
      automated lumbar nucleotomy, a prospective cohort study was performed with follow
      up CT within four to six hours after treatment of 97 discs in 88 patients. The CT
      scans were normal at 47 levels and abnormal at 50. At 11 levels traces of blood
      were seen along the trajectory, of which nine were located in the subcutaneous
      fat, one in the extensor and one in the psoas muscle. Small gas collections were
      observed at 42 levels. Twenty-one of them were located in the extensor and two in
      the psoas muscle, seven in the subcutaneous fat, two in the epidural space and
      ten in multiple locations. The abnormal scans were not associated with clinical
      symptoms different from those with normal scans. The results support previous
      reports indicating that this procedure is associated with low morbidity and
      complication rates.

PMID- 20682110
TI  - Eloquent pictures. "Linea splendens".

PMID- 20682112
TI  - Percutaneous Therapy of a Post-surgical Suboccipital Cerebrospinal Fluid Fistula
      with Fibrin Glue.
AB  - SUMMARY: The successful therapy of a suboccipital cerebrospinal fluid fistula by
      the percutaneous introduction of fibrin glue under computed tomographic guidance
      is described.

PMID- 20682111
TI  - Occlusion of the internal carotid artery based on a simple tolerance test.
AB  - SUMMARY: In order to evaluate the safety of the internal carotid artery (ICA)
      occlusion based on our simple tolerance test, we reviewed 142 consecutive
      tolerance tests. Permanent endovascular ICA occlusion was performed on 99; a
      tolerance test only was performed on the remaining 43. Our assessment consisted
      of 1) angiographic evaluation of collateral circulations without and with ICA
      test occlusion, 2) evaluation of clinical tolerance to balloon ICA occlusion for
      15-20 minutes. Complications of test and permanent ICA occlusion were
      retrospectively analyzed. Complications related to test occlusion occurred in 2
      cases (1.4%) without causing permanent deficits. Complications related to
      permanent occlusion occurred in 16 cases (16%) including 2 technical, 10
      temporary (10%) and 4 permanent (4%). Complications were significantly decreased
      after introduction of stringent postoperative care to prevent hypotension in
      1987. Since 1988, we performed 47 permanent ICA occlusion and experienced no
      technical, 3 temporary (6%) and no permanent complications. Our method to
      evaluate tolerance to ICA occlusion is simple and safe. Reliability of the
      results is comparable to other more complicated methods of assessing ICA
      occlusion.

PMID- 20682113
TI  - Editorial. You said anatomy?

PMID- 20682114
TI  - Aneurysmal Malformations of the Vein of Galen. Follow-up of 120 Children Treated
      between 1984 and 1994.
AB  - SUMMARY: The Vein of Galen Aneurysmal Malformation (VGAM) is regarded as a lesion
      with high morbidity and mortality, both spontaneously and under treatment, in
      part due to an incomplete appreciation of the effects of the lesion on the
      specific physiology of young children. In addition, various techniques have been
      applied over a short period of time to treat the lesion rather than the disorders
      it creates. We report experience with 120 consecutive cases of VGAM managed over
      the past ten years: 24 were diagnosed antenatally; 50 presented in the neonatal
      period with haemodynamic disturbance; 35 in infants presented with secondary
      hydrovenous disorders (macro crania, subependymal atrophy and ventricular
      dilatation); 12 were seen in children. We were unable to follow 10% of the
      patients because the referring teams decided not to follow our therapeutic
      advice. Treatment was contra-indicated in 17% of cases (with early brain damage
      and a rapidly fatal outcome). There were five (4%) which thrombosed spontaneously
      (but only two of these were neurologically normal). Embolisation was performed in
      78 patients via a transarterial femoral approach using glue. Anatomical cure has
      already been achieved in 53%. Of the treated patients, even when treatment has
      not been completed, 80% are growing neurologically normal. Permanent neurological
      deficit or irreversible neurocognitive delay related to the natural history of
      the lesion were evident in 8.5%. Overall mortality was 9%. These figures confirm
      that previous views on the prognosis of VGAM should be revised. Endoarterial
      embolisation, is the preferred treatment to date.

PMID- 20682115
TI  - Radiosurgery Following Embolisation and/or Surgery of Brain AVM's.
AB  - SUMMARY: A series of 45 patients who have undergone combined treatment for
      cerebral arteriovenous malformations (AVM's) is presented. All patients underwent
      additional radiosurgery after endovascular and/or surgical treatment.
      Stereotactic radiosurgical treatment using the Gamma knife has been available in
      our institution since 1992. The treatment strategy for brain AVM's has changed
      since that time. The possibility for total cure of partially embolised AVM's,
      where other treatment options had been exhausted, increased with adjunctive
      radiosurgery. Complex or giant AVM's in eloquent areas can now be treated using
      radiosurgery after embolisation and/or microsurgery, with minor risk of
      neurological deficit. In all 45 patients treated since September 1992 at the
      University of Vienna, embolisation was performed to reduce the size of the nidus
      in order to facilitate surgical resection or radiosurgical treatment. In 37
      patients radiosurgery was performed after endovascular treatment only, and in 8
      patients radiosurgery was performed after embolisation and surgery. All AVM's
      were classified according to Spetzler's Grading System(1). 31 patients (68.9%)
      were classified as Grade 3 or 4. Two patients (4.5%) were classified as. Grade 5.
      In a mean follow up time of 16 months (range 2-40), there were 15 complete
      obliterations and 2 patients with unexpected residual AV M after two years. Of
      patients who required staged radiosurgical therapy, 12 have been followed for
      less than two years after their final procedure. In an additional 12 patients the
      follow-up period is less than 12 months. 4 patients were lost to follow up. There
      is a morbidity of 8.8% and no mortality in this patient group.

PMID- 20682116
TI  - Cervical automated discectomy. Report of 150 cases and evolution in the
      management of failure cases.
AB  - SUMMARY: The lumbar automated discectomy system described by Onik has been used
      in the treatment of cervical disk herniations whose symptomatology resisted
      medical treatment. Experience on 150 patients is reported showing a 74.5% success
      rate. This series performed in most cases on an outpatient basis had no
      complications. Up to 1992 failure cases were treated by intradiscal injections of
      triamcinolone with 62 % of success. This complementary technique was abandonned
      after the description of epidural calcifications secondary to this type of
      injections in the lumbar area. Since 1992, failure cases have been managed
      differently with injections of steroids in the cervical joints, especially when a
      hypertrophy of the ligamentum ftavum supposedly a sign of an inflammatory
      posterior component of the pain was demonstrated on the CT. Nine patients
      received intradiscal injections of microdoses (600IU) of chymopapaine with
      excellent results. No patient has had open surgery since 1992. It is concluded
      that percutaneous automated discectomy is a very promising and safe technique
      which can be used as a first choice technique for most cervical disk herniations
      resisting medical treatment.

PMID- 20682117
TI  - Evocative images.

PMID- 20682118
TI  - Medical treatment of congestive cardiac failure from cerebral arteriovenous
      fistulas at bicetre hospital.
AB  - SUMMARY: Arteriovenous fistulas create an increase in venous return and
      subsequent right heart overload. The result is right heart dilatation, pulmonary
      arterial hypertension, and increased pulmonary blood flow. Reduction in arterial
      diastolic pressure (as observed in arteriovenous shunt), an increase in end
      diastolic pressure (due to increased preload), a reduction in diastolic period
      (due to tachycardia) are all detrimental to myocardial perfusion and hence oxygen
      delivery and may precipitate left ventricular failure. Furthermore, the
      transition from a foetal circulatory pattern to an adult circulatory pattern is
      complex and both pulmonary and systemic circulations remain highly unstable
      during the first week after birth. This can explain a persistent transitional
      circulation with shunts through the ductus arteriosus, the foramen ovale and a
      pulmonary hypertension which worsen the systolic and diastolic wall stress. The
      clinical presentation depends on the size of the left-to-right shunt and its
      tolerance. The aims of symptomatic therapy are to improve oxygen delivery to the
      tissues and decrease tissue oxygen consumption. Measures that improve the
      patient's effective ventilation, arterial oxygen saturation, and hematocrit need
      to be the first steps. Diuretics are the first step for reducing preload. Cardiac
      output can be improved by increasing cardiac contractility with inotropic agents.
      Digoxin is the main agent used to increase myocardial contractility. However, its
      use in a hyperkinetic state due to arteriovenous fistulas remains controversial:
      pretreatment myocardial function indices may already be above normal, and there
      is no clear evidence that their further increase produces clinical benefit.
      Vasodilators are obviously contraindicated if systemic arterial pressure is low.
      If the failure cannot be controlled, embolisation of the lesion should be
      considered. The goal of this paper is to provide a rational approach to the
      treatment of circulatory failure due to cerebral arteriovenous shunts.

PMID- 20682119
TI  - Paraplegia due to rupture of an anterior communicating artery aneurysm.
      Consequence of a rare anatomic variant of the A2 segment.
AB  - SUMMARY: A 44-year-old patient developed paraplegia following rupture of an
      anterior communicating artery aneurysm. There was no evidence of any spinal
      lesion. Cerebral angiography showed a paired bihemispheric disposition of the A2
      segment. We report this case and consider the anatomical variants of the A2
      segment described in literature. The paired bihemispheric variant was reported in
      21% of the cases. An azygos (unpaired) artery was observed in 5% and a
      triplicated A2 segment in 20% of the cases.

PMID- 20682120
TI  - Meeting minutes. A meeting of neurosurgeons and therapeutic neuroradiologists.
      Fondation "les treilles" (tourtour / salernes - france) june 1995.

PMID- 20682121
TI  - Editorial. European works ahead.

PMID- 20682122
TI  - Editorial. Ethical considerations relating to writing a medical scientific paper
      for publication.

PMID- 20682123
TI  - Usefulness of intravascular Doppler flow measurements in cerebral endovascular
      treatment. A comparison with trans cranial Doppler.
AB  - SUMMARY: Measurement of cerebral blood flow in cerebral endovascular procedures
      is useful for the assessment of treatment effects. We used transcranial Doppler
      sonography (TCD) and Doppler guide wires (SmartWire((R)), Cardiometries Co.) in
      intravascular treatment. The cases were 6 brain arteriovenous malformations
      (AVM), 2 carotid cavernous fistulas (CCF), 2 facial angiomas, and 2 carotid
      stenoses. Intravascular cerebral blood flow measurements with the SmartWire were
      performed during the endovascular procedure. TCD was used pre- and post
      endovascular treatment, and velocity, pulsatility index (PI) and resistance index
      (RI) were compared with the SmartWire. For both TCD and Smart Wire, blood
      velocity of the main artery decreased, and PI and RI were improved after
      embolisation of AVM. In angioplasty cases, post stenotic flow velocity, as
      measured by SmartWire, was improved, and the flow of MCA measured with TCD was
      also improved after treatment. The SmartWire is useful to assess cerebral blood
      flow changes during the neuroendovascular procedure. Combined with repeated
      follow up with TCD, Doppler flow measurements are useful to assess the effect of
      endovascular treatment.

PMID- 20682124
TI  - Local intraarterial thrombolysis in the carotid territory.
AB  - SUMMARY: A new series of 142 patients treated by local intraarterial thrombolysis
      is presented. After haemorrhage was ruled out by CT, all patients had an
      emergency angiogram. Patients with occlusion of the lenticulostriate arteries
      were not treated after the sixth hour (79 cases). Patients without involvement of
      these arteries were treated up to the 12th hour (61 cases). This selection led to
      a dramatic reduction of post-thrombolysis intraparenchymatous haemorrhage (0.7%)
      compared to other series. All deaths (7 cases) were related to vasogenic oedema
      due to incomplete reduction of infarcted cerebral volume, in most cases (4 cases)
      in intracerebral extension of a cervical internal carotid occlusion. Digitized
      parenchymography proved to be a reliable technique to document the exact location
      and extent of brain ischaemia before and after thrombolysis. It also allows a
      prognosis of spontaneous recovery without using thrombolysis. By reducing the
      infarcted cerebral volume, local intraarterial thrombolysis seems beneficial to
      the patient as long as a strict selection based on the angiographic location of
      the occlusion and the time delay is respected.

PMID- 20682125
TI  - Follow-up MR of Intracranial Cavernomas The Relationship between Haemorrhagic
      Events and Morphology.
AB  - SUMMARY: The purpose of this review was to determine whether a classification
      scheme for cavernomas based on the MR appearance is predictive of the natural
      history of the lesions with particular reference to the risk of haemorrhage. We
      reviewed the clinical and MR findings in 156 patients with intracranial
      cavernomas. The dominant or symptomatic cavernoma was graded into three groups
      according to the appearance of the blood products. The presence of haemorrhage,
      mass effect and oedema was evaluated. Sixty patients had serial MRs with a mean
      follow-up of 1.9 years. Subacute haemorrhage with mass effect and oedema was
      evident on the initial MR in 30 patients (19%). In seven patients follow-up MR
      showed haemorrhage with mass effect and oedema. Six of these bleeds were in the
      posterior fossa. The haemorrhages seen on follow-up MR occurred in all three
      morphological types. Regression was found on follow-up MR in five of the seven
      patients who initially showed a bleed. In 35% of patients, the dominant or
      symptomatic cavernoma changed on serial MR. Intracranial cavernomas are dynamic
      lesions with both active and regressive changes seen on follow-up MR. A
      classification system based on morphology was not found to be useful in
      predicting future bleeds. Bleeding rates, based on MRfollow-up, were 10.9% in the
      posterior fossa and 1.7% in the supratentorial compartment.

PMID- 20682126
TI  - Anatomic variations and pathologic conditions as risk factors of complications in
      percutaneous lumbar nucleotomy.
AB  - SUMMARY: This study was carried out to assess anatomic variations and pathologic
      changes associated with a potentially increased risk of complications during
      percutaneous nucleotomy. The MRI and CT examinations of 88 patients were reviewed
      with regard to the positional relationship between the trajectory to the disc and
      the bowel and iliac vessels respectively at the L4-L5 and L5-S1 levels.
      Pathologic conditions involving the anterior part of the annulus were assessed
      both by MRI and by CT-discography of 97 discs. The shortest distance from the
      needle course to the bowels was 29 mm. At ten other disc levels this distance was
      less than 40 mm. The position of the bowels is influenced by the size of the
      patient, the size and course of the psoas muscles and the amount of
      retroperitoneal fat. The bowels are at greaten distance from the trajectory at
      the L5-S1 than at the L4-L5 level. The risk of bowel puncture seems to be
      minimal. The iliac vessels were positioned behind the midportion of the disc in
      three patients. There was greater variation and a shorter distance to the
      trajectory at the L5-S1 than at the L4-L5 level. Anterior disc hernias, and
      particularly severe annular degeneration involving the anterior part of the
      annulus are frequently seen. These conditions include a weakening of the annulus
      and may increase the risk of anterior perforation during nucleotomy.

PMID- 20682127
TI  - Acute-Sinus Thrombosis in a Child with Antibodies against Cardiolipins. Report of
      a Case Treated with Local Fibrinolysis.
AB  - SUMMARY: A case of thrombosis of the straight sinus and the left transverse sinus
      in an 11 year old boy is described. The patient had a history of slight trauma
      followed by infection of the upper airways and presented with severe impressive
      and expressive dysphasia and stupor. He was treated with in situ fibrinolysis.
      Despite successful local fibrinolysis and thrombectomy with a balloon catheter
      the patient rethrombosed his left transverse sinus several times and had a late
      thrombosis of his jugular vein. Nevertheless, flow in the left sigmoid sinus was
      facilitated and focal brain oedema was significantly reduced. Serum levels of
      antibodies against cardiolipins, associated with venous thrombosis, were elevated
      and interfered with reagents used for measuring the activated partial
      tromboplastin time, causing it to be falsely prolonged with subsequent
      underdosage of heparin. He was treated with oral anticoagulants for one year
      after the episode and recovered completely.

PMID- 20682128
TI  - Quantified partial embolisation in a vein of galen malformation with congestive
      cardiac failure.
AB  - SUMMARY: The aim of the study was to quantify embolisation in a vein of Galen
      malformation by intraluminal measurements of flow velocities in the feeding
      vessels and to test a new O.014-inch Doppler guide wire in the paediatric
      population. The examination was performed in a seven month old boy who presented
      with a vein of Galen malformation combined with congestive cardiac failure from
      birth. The measurements showed a decrease of the systolic and diastolic
      velocities and an increase in the effective downstream vascular resistance after
      closure of the high flow fistula. The decrease of the diastolic velocities after
      embolisation was more prominent because of the reduction of the sump effect
      responsible for the high diastolic velocity before embolisation. The reduction of
      about 40% of the vein of Galen malformation estimated with morphological criteria
      was associated with a decrease of the diastolic velocity in the basilar artery of
      about 50%. The clinical improvement led to the discontinuance of most of the
      cardiac treatment over a few days. These measurements seem to offer the
      possibility to assess the necessary reduction of the shunt to relieve CCF in a
      vein of Galen malformation.

PMID- 20682129
TI  - Motor cortex activation in a patient with arteriovenous angioma in the left
      region.

PMID- 20682130
TI  - Review of the literature. Abstract from acta neurochirurgica and surgery for
      cerebral stroke (Japan).

PMID- 20682131
TI  - Linear correlation between phenobarbital dose and concentration in alcohol
      withdrawal patients.
AB  - INTRODUCTION: Barbiturates are potent drugs for treatment of alcohol withdrawal
      symptoms, but they entail a risk of over-dosage and respiratory depression. The
      purpose of the present study was to investigate the correlation between
      phenobarbital dose and phenobarbital blood concentration in patients withdrawing
      from long-term alcohol intoxication. MATERIAL AND METHODS: A total of 497
      patients who were hospitalized for treatment of alcohol withdrawal symptoms
      during an 18-month period were enrolled in the study. Phenobarbital 200 mg was
      administered orally every 30 or 60 minutes in response to the observed symptoms.
      Within the first 24 hours after admission, i.e. at 8 AM, blood was collected for
      determination of phenobarbital concentration, and the cumulated dose of
      phenobarbital at the time of the blood sampling was registered. RESULTS: The mean
      cumulated phenobarbital dose at the time of the blood sampling was 877 mg +/- 557
      mg, while the mean plasma phenobarbital concentration was 104 micromol/l +/- 62
      micromol/l. A statistically significant linear correlation between phenobarbital
      dose and concentration was found for both males and females as 83% and 84% of the
      variation in drug concentration, respectively, could be explained by the
      phenobarbital dose. We observed no serious complications of the phenobarbital
      treatment--including respiratory problems or severe sedation. DISCUSSION: The
      strong linear correlation between phenobarbital dose and concentration suggests
      that absorption of plasma phenobarbital from the gastrointestinal system is
      highly predictable.

PMID- 20682132
TI  - An evaluation of the 18- and 12-month basic postgraduate training programmes in
      Denmark.
AB  - INTRODUCTION: It was decided that the Danish 18-month internship training should
      be replaced by a 12-month postgraduate training period including six months of
      employment at a hospital ward and six months at a general practice/hospital ward.
      This study examines how the physicians from the old and new programmes evaluate
      their training, and it explores their attitudes towards the new postgraduate
      training programme. MATERIAL AND METHODS: We developed a questionnaire by which
      quantitative and qualitative data were collected. The questionnaire was sent to
      all physicians following basic postgraduate training in 2009. A total of 1,034
      doctors were invited to answer the questionnaire. One quarter of these followed
      the 12-month programme and three quarters followed the 18-month programme. The
      response rate was 66%. RESULTS: Doctors following the new 12-month programme felt
      less professionally equipped and less ready for continued specialisation than
      doctors of the 18-month programme and they requested a downward adjustment of the
      learning objectives associated with the educational positions which follow their
      basic training. Physicians do not expect the increased focus on learning and
      supervision to compensate for the six-month reduction of the training period.
      Internal medicine should be included in the basic postgraduate training of all
      physicians. Training in secondary as well as primary health care was requested.
      CONCLUSION: The young physicians were reluctant towards the new basic
      postgraduate training programme.

PMID- 20682133
TI  - Phenobarbital versus diazepam for delirium tremens--a retrospective study.
AB  - INTRODUCTION: Delirium tremens (DT) is a severe and potentially fatal condition
      that may occur during withdrawal from chronic alcohol intoxication. The purpose
      of the present study was to compare the effects and the rates of complications of
      phenobarbital and diazepam treatment in DT. MATERIAL AND METHODS: Data were
      collected retrospectively from the medical files of patients who had received DT
      treatment (n = 194) at two psychiatric departments located in the general
      Copenhagen area in the 1998-2006 period. At one department, all patients were
      treated with phenobarbital (n = 53), while the treatment regimen at the other
      department was changed from phenobarbital (n = 53) to diazepam (n = 88) in 2002.
      RESULTS: Length of DT and hospitalization, mortality and rate of pneumonia (26%)
      were not affected by treatment. A subpopulation (9%) in the diazepam group was
      resistant to treatment. Respiratory depression occurred in 4% of the
      phenobarbital and in 1% of the diazepam-treated patients. Wernicke's
      encephalopathy was established in 47% of the patients. CONCLUSION: Phenobarbital
      is a safe alternative to diazepam in the treatment of DT.

PMID- 20682134
TI  - Expert opinion on "best practices" in the delivery of health care services to
      immigrants in Denmark.
AB  - INTRODUCTION: Delivery of health care to immigrants is an emerging field of
      interest. Immigrants are frequently characterised by health outcomes that are
      inferior to those of other groups with regard to morbidity and mortality. In
      addition, health professionals report difficulties associated with the encounter
      with immigrant patients. MATERIAL AND METHODS: A Delphi process with eight Danish
      experts from the field of immigrant health was performed as part of an EU
      project. The objective of the Delphi process was to investigate expert opinion on
      "best practice in the delivery of healthcare to immigrants". Initially, 60
      factors were suggested by the experts. Next, these factors were summarised into
      32 factors that the experts were invited to rate and, if possible, agree on.
      RESULTS: The top 11 factors identified in the Delphi process were access to
      interpreters, quality of interpretation, ensuring medication compliance, having
      sufficient consultation time, coherence of offers, interdisciplinary
      collaboration, allocation of resources, the role of the practitioner,
      acknowledgement of the individual patient, education of health professionals and
      students and access to telephone interpretation to supplement other services.
      CONCLUSION: The Delphi process can be a valuable tool in the investigation of
      expert opinion and may thereby help to guide future policy directives. In the
      light of the importance experts placed on access to interpreters and on the
      quality of the interpretation services offered, it seems as an untenable strategy
      to introduce as from June 2011 self-payment for interpretation services provided
      to immigrants who have stayed in the country for more than seven years.

PMID- 20682135
TI  - Objective determination of Fitzpatrick skin type.
AB  - The overall aim of this Ph.D. project was to clarify what the subjective
      Fitzpatrick skin type represents with regard to the skin's reaction to UVR.
      Fitzpatrick skin type is used as an expression of the constitutive UV
      sensitivity. It has been used for guiding dose-levels in phototherapy and is an
      important risk factor for skin cancer. The subjective Fitzpatrick skin type and
      the measured skin type PPF (pigment protection factor, calculated based on a skin
      reflectance measurement, predicts the UV-dose (SED) to give 1 MED) were
      investigated parallelly in relation to the clinically determined dose to erythema
      (MED) and/or pigmentation (MMD) to determine which one related best. PPF is an
      established method for assessing UV-sensitivity by predicting SED to MED. UV-dose
      to MED and/or MMD was determined after single UV-exposure to Solar Simulator on
      nates (n= 84) and after single and multiple (5, 6 or 12) UV-exposures (n = 24-62)
      on the back to four UV-sources (nUVB, Solar, bUVA and UVA1). SED to MMD was also
      related to wavelength. MED was only determined after a single and four UV
      exposures to narrowband UVB (nUVB) and Solar Simulator (Solar). Volunteers with a
      broad range of constitutive pigmentation (skin types I-V) were included. Equal
      MMD doses (predetermined after a single UV-exposure) were used at the multiple
      exposures. The absolute increase in pigmentation after 6 and 12 UV-exposures,
      where steady-state pigmentation was reached, was independent of skin type and
      therefore could not enter into the calculations. But it proved that the MMD
      determinations after single exposure were correct and could be used at multiple
      UV-exposures. In contrary to what we expected, our results indicate that people
      may refer to the constitutive pigmentation, when they reply to the question of
      Fitzpatrick skin type. This applied to both erythema and pigmentation response as
      both dose to MED and MMD showed a better correlation to nates than to the back.
      As expected, our results from the back indicate that people seem to refer to sun
      sensitivity after multiple exposures to the sun rather than a single sun
      exposure, when they reply to the question of Fitzpatrick skin type. Hence, both
      SED to MED and SED to MMD are better correlated to skin type after respectively 4
      and 5 exposures to Solar Simulator and nUVB compared to 1 exposure. Only when
      tanning is preceded by erythema there is a relation between SED to MMD and skin
      type/PPF. Thus only after nUVB and Solar. For nUVB and Solar there was a linear
      relation between erythema and tanning ability with the intercept different from
      zero. In spite of what we expected based on the literature, the correlation was
      better between SED to MED and skin type than between SED to MMD and skin type.
      This applied to single and multiple exposures and to single calculations and
      multiple regression analyses. The long-waved UVA1 and broadband UVA should
      definitely not be used for skin type determination, as there was no relation
      between MMD and skin type/PPF. Both nUVB and Solar can be considered. Finally,
      based on the objective parameters: pre-exposure pigmentation measured by skin
      reflectance, MED and MMD we tried to predict the Fitzpatrick skin type by
      multinominal logistic regression analyses to evaluate the significance of the
      different parameters for the subjective skin type classification and thereby
      hopefully enlighten what Fitzpatrick skin type represents. For single UV-exposure
      only the pre-exposure pigmentation worked as a predictor of Fitzpatrick skin
      type, and that is what PPF is based on. When this parameter was removed, only SED
      to MED was significant. Our model succeeds better to classify people correct
      after multiple UV-exposure compared to a single UV-exposure. PPF was predicted
      likewise and was highly correlated to SED to MED, as expected, and even higher
      correlated to Fitzpatrick skin type. SED to MMD was not significant. This study
      confirms that Fitzpatrick skin type is an unreliable predictor of UV-sensitivity
      with regard to MED- and MMD test. Fitzpatrick skin type in epidemiological
      context (risk for skin cancer) stands for burns and ability to tan may represent
      "cumulative" dose. SED to MED is equivalent to burns. PPF may also indirectly
      represent cumulative dose--the less pigmented the skin the more UVR penetrates
      the epidermis and will be able to accumulate and induce skin cancer. Our results
      indicate that Fitzpatrick skin type predominantly is determined by the skin
      pigmentation and that the second most important objective parameter is SED to MED
      (and not SED to MMD). This explains why Fitzpatrick skin type, eventhough being
      an unreliable predictor of UV-sensitivity, still plays an important role in
      epidemiology with regard to estimation of risk of skin cancer. This study showed
      that PPF can predict the UV-sensitivity also with regard to the tanning ability
      (MMD), can be applied to multiple UV-exposures and to a broader pigmentation
      spectrum. PPF is preferred to predict the individual UV-sensitivity rather than
      the subjective Fitzpatrick skin type, confirmed for both nates and back, single
      as well as repetitive UV-exposures. It should therefore be considered to
      concentrate on skin reflectance measurements.

PMID- 20682136
TI  - Nasal nitric oxide and pulmonary radioaerosol mucociliary clearance as
      supplementary tools in diagnosis of primary ciliary dyskinesia.
AB  - Primary ciliary dyskinesia (PCD) is a rare, usually autosomal recessive inherited
      disorder, characterized by abnormalities in ciliary structure and/or function.
      Frequent, intermittent or chronic airway infections precipitated by impaired
      airway mucociliary clearance may cause permanent lung damage and reduced lung
      function. Early diagnosis is considered important for the prevention of lung
      damage, but diagnosis is probably often delayed or even missed since diagnosis of
      PCD is both complex and time consuming, and yet not always exact. The aims of
      this PhD thesis were to evaluate the discriminative capacity and "real-life"
      clinical application of two candidates for supplemental diagnostic testing for
      PCD: Nasal nitric oxide (nNO) measurement placed as a first line test to point
      out probable PCD patients for further investigation or exclude patients,
      regardless of age, Pulmonary radioaerosol mucociliary clearance (PRMC) as a
      second line test for PCD investigation in children from 5 years of age. And
      additionally, Proposing an algorithm for the pathway of diagnosing PCD based on
      these two studies and recommendations from the literature. Nasal NO and PRMC
      demonstrated to be two highly valid supplementary diagnostic tools to be placed
      in each end of the diagnostic pathway when investigating selected patients
      referred for PCD work up. Nasal NO measurement demonstrated to have an obvious
      place as a first line test in the pathway of PCD investigation and PRMC as second
      line test as a supplement to ciliary function test and EM-test in cases of
      difficult diagnoses. Neither of these tests can stand alone in diagnosis or
      excluding of PCD. PCD remains to be a diagnosis that should be made at a tertiary
      PCD centre, as clinical evaluation of referred patients is crucial before
      excluding the disease.

PMID- 20682137
TI  - Improving patient care and reducing unintended pregnancy: translating new
      guidelines into effective practice.

PMID- 20682138
TI  - Adaptation of the World Health Organization's medical eligibility criteria for
      contraceptive use for use in the United States.
AB  - BACKGROUND: The Centers for Disease Control and Prevention (CDC) recently adapted
      global guidance on contraceptive use from the World Health Organization (WHO) to
      create the United States Medical Eligibility Criteria for Contraceptive Use
      (MEC). This guidance includes recommendations for use of specific contraceptive
      methods by people with certain characteristics or medical conditions. STUDY
      DESIGN: CDC determined the need and scope for the adaptation, conducted 12
      systematic reviews of the scientific evidence and convened a meeting of health
      professionals to discuss recommendations based on the evidence. RESULTS: The vast
      majority of the US guidance is the same as the WHO guidance and addresses over
      160 characteristics or medical conditions. Modifications were made to WHO
      recommendations for six medical conditions, and recommendations were developed
      for six new medical conditions. CONCLUSION: The US MEC is intended to serve as a
      source of clinical guidance for providers as they counsel clients about
      contraceptive method choices.

PMID- 20682139
TI  - Combined oral contraceptive use among breastfeeding women: a systematic review.
AB  - BACKGROUND: Postpartum women need effective contraception, but using hormonal
      contraceptives may affect breastfeeding performance and infant health outcomes.
      STUDY DESIGN: We searched the MEDLINE and Cochrane databases for all articles
      published through May 2009 for primary research studies that investigated
      clinical outcomes among breastfeeding women who used hormonal contraception or
      their infants. RESULTS: Three randomized controlled trials reported decreased
      mean duration of breastfeeding and higher rates of supplemental feeding among
      combined oral contraceptive (COC) users than among nonusers, while one
      multicountry trial found no differences in these parameters. Only one study
      demonstrated lower average weights during the first year of life for infants
      whose mothers used COCs while breastfeeding. None of the eight studies, four of
      which were observational, included in this review documented adverse infant
      health outcomes. CONCLUSIONS: Limited evidence demonstrates an inconsistent
      effect of COC on breastfeeding duration and success. The evidence is inadequate
      to determine whether a mother's use of these drugs affects breastfeeding duration
      or the infant's health.

PMID- 20682140
TI  - Progestogen-only contraceptive use among breastfeeding women: a systematic
      review.
AB  - BACKGROUND: The use of progestogen-only contraceptives by breastfeeding women
      raises theoretical concerns regarding possible adverse effects on breastfeeding
      success, and infant health or growth. This review was conducted to determine from
      the literature whether use of progestogen-only contraceptives by breastfeeding
      women leads to adverse effects on lactation, or infant growth or health when
      compared to nonuse. STUDY DESIGN: We searched the Medline, Popline, Cochrane and
      LILACS databases for all articles published from database inception through May
      2009. Studies were included if they investigated the use of progestogen-only
      methods in breastfeeding women and reported on clinical outcomes in either women
      or their infants. Standard data abstraction templates were used to systematically
      assess and summarize. Summary odds ratios were not calculated, given the
      heterogeneity of interventions, results and non-quantifiable outcomes reported.
      RESULTS: We identified 43 articles for this review. Overall, five randomized
      trials and 38 observational studies demonstrated no adverse effects of various
      progestogen-only methods of contraception on multiple measures of breastfeeding
      performance through 12 months in women using these methods in the postpartum
      period. Many of these studies also demonstrated no adverse effects of progestogen
      only methods on infant growth, health or development from 6 months to 6 years of
      age. Additional studies demonstrated no effects on infant immunoglobulins or sex
      hormones of exposed male infants. A single study of a desogestrel pill reported
      two cases of gynecomastia in exposed infants. CONCLUSIONS: Evidence suggests that
      progestogen-only methods of contraception do not adversely affect breastfeeding
      performance when used during lactation. Evidence that progestogen-only
      contraception does not adversely affect infant growth, health, or development
      when used by breastfeeding women is consistent but methodologically limited.

PMID- 20682141
TI  - Intrauterine device use among women with ovarian cancer: a systematic review.
AB  - BACKGROUND: Fertility-sparing treatment may be an option for women with early
      stage ovarian cancer and certain tumor types. This systematic review evaluated
      the evidence on the safety of intrauterine device (IUD) use by women with ovarian
      cancer. STUDY DESIGN: We searched the PubMed database for peer-reviewed articles
      relevant to IUD (copper or levonorgestrel-releasing) use and ovarian cancer
      published in any language from database inception through August 2009. We sought
      studies that examined outcomes among women using an IUD at or after ovarian
      cancer diagnosis. RESULTS: Of the 250 articles identified by our search strategy,
      none provided evidence (direct or indirect) regarding the safety of IUD use among
      women with ovarian cancer. CONCLUSIONS: No evidence on the safety of IUD use
      among women with ovarian cancer was identified. While there are some theoretical
      concerns that IUD use might affect monitoring of disease progression of sex cord
      stromal tumors, or increase risk of pelvic infection or vaginal bleeding among
      women undergoing chemotherapy, we did not find any data to suggest that IUD use
      would lead to worsening of primary ovarian cancer.

PMID- 20682142
TI  - Intrauterine device use among women with uterine fibroids: a systematic review.
AB  - BACKGROUND: There are concerns that intrauterine device (IUD) use by women with
      uterine fibroids might increase their uterine bleeding or risk for device
      expulsion. The objective of this systematic review was to evaluate evidence
      concerning the safety and effectiveness of IUD use among women with uterine
      fibroids. Key questions included whether IUD use is associated with increased
      risk for uterine bleeding among women with uterine fibroids and whether the
      presence of uterine fibroids is associated with an increased risk for device
      expulsion among IUD users. STUDY DESIGN: We searched the PubMed database for peer
      reviewed articles relevant to IUD (copper or levonorgestrel-releasing) use and
      uterine fibroids published in any language from database inception through June
      2009. We used standard abstract forms and a grading system to summarize and
      assess the quality of the evidence. RESULTS: From 202 articles found in the
      database search, we identified 11 studies that met our inclusion criteria, all of
      which examined outcomes among users of the levonorgestrel-releasing IUD (LNG
      IUD). Evidence from 10 of 11 noncomparative studies (Level II-3, fair) suggests
      that LNG-IUD use among women with fibroids does not increase menstrual bleeding,
      and results from all 11 showed that menstrual blood loss decreased among women
      who continued to use the LNG-IUD through the end of the study period. Overall,
      serum levels of hemoglobin, hematocrit and ferritin increased among LNG-IUD users
      in studies that assessed these outcomes. Several studies reported some
      occurrences of irregular bleeding. Findings from two cohort studies (Level II-2,
      fair to poor) showed rates of LNG-IUD expulsion to be higher among women with
      uterine fibroids (11% in each) than among women without uterine fibroids (0% and
      3%); however, in one study the difference was not statistically significant, and
      in the other significance testing was not conducted. Six prospective
      noncomparative studies reported expulsion rates of 0-20% among women with uterine
      fibroids. CONCLUSIONS: Most women with uterine fibroids are likely to have less
      menstrual blood loss and higher serum levels of hemoglobin, hematocrit and
      ferritin after insertion of an LNG-IUD, despite some occurrences of irregular
      bleeding. LNG-IUD users with uterine fibroids may have higher rates of expulsion
      than those without fibroids.

PMID- 20682143
TI  - Use of contraceptive methods among women with endometrial hyperplasia: a
      systematic review.
AB  - BACKGROUND: The objective of this systematic review is to evaluate the evidence
      for the safety of contraceptive use among women with endometrial hyperplasia.
      STUDY DESIGN: We searched the PubMed database for peer-reviewed articles
      published in any language from database inception through February 2009
      concerning the safety of using any contraceptive method among women diagnosed
      with endometrial hyperplasia. We excluded case reports but included all other
      study designs. The quality of each individual piece of evidence was assessed
      using the United States Preventive Services Task Force grading system. RESULTS:
      We identified nine articles that met the criteria for review. Each study examined
      levonorgestrel intrauterine devices (LNG-IUDs); no studies were identified that
      examined other contraceptive methods. Overall, these studies suggest that LNG-IUD
      use is not associated with adverse health events among women diagnosed with
      endometrial hyperplasia. Disease regression with LNG-IUD use was observed in all
      women in seven studies, in 90% of women in one study, and in 67% of women in one
      study. Limitations of the studies include small sample sizes and lack of a
      comparison group or nonrandomized assignment to LNG-IUD. CONCLUSIONS: There is
      fair quality evidence indicating that use of the LNG-IUD is safe for women with
      endometrial hyperplasia and may have therapeutic benefits.

PMID- 20682144
TI  - Safety of contraceptive methods for women with rheumatoid arthritis: a systematic
      review.
AB  - BACKGROUND: Women with rheumatoid arthritis (RA) and their clinicians may have
      unique concerns about certain methods of contraception. STUDY DESIGN: We
      conducted a systematic review of the literature in the MEDLINE database through
      February 2009 for peer-reviewed journal articles on use of any method of
      contraception, or progestins or estrogens, and progression of RA. RESULTS: We
      identified eight articles that met the inclusion criteria: six examined oral
      contraceptives (OCs), one progesterone, and one estrogen. We found no studies on
      other methods of contraception. For OCs, no consistent pattern of improvement or
      worsening of disease emerged and most patients showed little change in RA
      symptoms. We saw little improvement in the studies examining progesterone and
      estrogen. CONCLUSION: Although sparse and based primarily on older studies of
      poor quality, this information suggests that OC use is unlikely to affect RA
      disease progression. Research is needed on other forms of contraception, such as
      DMPA and IUD.

PMID- 20682145
TI  - Contraceptive use among women with inflammatory bowel disease: A systematic
      review.
AB  - BACKGROUND: There are theoretical concerns that use of hormonal contraceptives by
      women with inflammatory bowel disease (IBD) might increase disease relapse and
      risk of other adverse health outcomes, including thrombosis. In addition, there
      are concerns that IBD-related malabsorption might decrease the effectiveness of
      orally ingested contraceptives. The objective of this systematic review was to
      evaluate the evidence on the safety and effectiveness of contraceptive use among
      women with IBD. STUDY DESIGN: We searched the PubMed database for peer-reviewed
      articles relevant to contraceptive use and IBD that were published in any
      language from inception of the database through February 2009. We used standard
      abstract forms and grading systems to summarize and assess the quality of the
      evidence. RESULTS: From 207 articles, we identified 10 studies that met our
      inclusion criteria. Evidence from five cohort studies (Level II-2, fair to good)
      suggests no increased risk of IBD relapse with use of oral contraceptives.
      Evidence from two pharmacokinetic studies (not graded) suggests that women with
      mild ulcerative colitis and those with an ileostomy following a proctocolectomy
      with small ileal resections have plasma concentrations of steroid hormones after
      oral ingestion of higher doses of combined oral contraceptives that are similar
      to the plasma concentrations among healthy volunteers. No studies were found that
      examined the risk of thrombosis among women with IBD who used hormonal
      contraceptives. CONCLUSIONS: Limited evidence suggests there is no increased risk
      of disease relapse among women with IBD who use oral contraceptives, and there
      seem to be no differences in the absorption of higher-dose combined oral
      contraceptives between women with mild ulcerative colitis and small ileal
      resections and healthy women.

PMID- 20682146
TI  - Contraceptive use among women with a history of bariatric surgery: a systematic
      review.
AB  - BACKGROUND: Weight loss after bariatric surgery often improves fertility but can
      pose substantial risks to maternal and fetal outcomes. Women who have undergone a
      bariatric surgical procedure are currently advised to delay conception for up to
      2 years. STUDY DESIGN: We conducted a systematic review of the literature, from
      database (PubMed) inception through February 2009, to evaluate evidence on the
      safety and effectiveness of contraceptive use among women with a history of
      bariatric surgery. RESULTS: From 29 articles, five met review inclusion criteria.
      One prospective, noncomparative study reported 2 pregnancies among 9 (22%) oral
      contraceptive (OC) users following biliopancreatic diversion, and one descriptive
      study reported no pregnancies among an unidentified number of women taking OCs
      following laparoscopic adjustable gastric banding. Of two pharmacokinetic
      studies, one found lower plasma levels of norethisterone and levonorgestrel among
      women having had a jejunoileal bypass, as compared to nonoperated, normal-weight
      controls. The other study found no difference in plasma levels of D-norgestrel
      between women having a jejunoileal bypass of either 1:3 or 3:1 ratio between the
      length of jejunum and ileum left in continuity, but women with a 1:3 ratio had
      significantly higher plasma levels of D-norgestrel than extremely obese controls
      not operated upon. CONCLUSIONS: Evidence regarding OC effectiveness following a
      bariatric surgical procedure is quite limited, although no substantial decrease
      in effectiveness was identified from available studies. Evidence on failure rates
      for other contraceptive methods and evidence on safety for all contraceptive
      methods was not identified.

PMID- 20682147
TI  - Safety of contraceptive use among women with peripartum cardiomyopathy: a
      systematic review.
AB  - STUDY DESIGN: Women with peripartum cardiomyopathy (PPCM) have significant health
      risks during subsequent pregnancies and therefore have a critical need for safe
      and effective contraception. This systematic review examines evidence regarding
      the safety of contraceptive use among women with PPCM. METHODS: We searched the
      PubMed database for all primary research articles published through February 2009
      that addressed the safety of any contraceptive method among women with PPCM or
      other cardiomyopathy of any type. RESULTS: Of 110 articles that addressed
      contraceptive safety among women with cardiac disease, three met our inclusion
      criteria. In these three studies, which included a total of five women with
      cardiomyopathy, though not specifically PPCM, cases of hypertension, transient
      ischemic attack (TIA), thromboembolism or heart failure were found among women
      with cardiac disease who used hormonal methods of contraception including
      combined oral contraceptives, progestin-only pills and depot medroxyprogesterone
      acetate. None of the studies reported any cases of cardiovascular complications
      or infective endocarditis among women with cardiac disease who used intrauterine
      devices (IUDs). CONCLUSIONS: We found no data concerning the safety of
      contraceptive use among women with PPCM, though we did find limited evidence of
      hypertension, TIA, thromboembolism and heart failure among women with cardiac
      disease who used hormonal methods of contraception. None of the studies reported
      any cases of cardiovascular complications or infective endocarditis among women
      with cardiac disease who used IUDs.

PMID- 20682148
TI  - Contraceptive use among solid organ transplant patients: a systematic review.
AB  - BACKGROUND: Women undergoing solid organ transplantation are advised to avoid
      pregnancy for up to 24 months following transplant surgery. STUDY DESIGN: We
      conducted a systematic review of the literature, from database (PubMed) inception
      through February 2009, to evaluate evidence on the safety and effectiveness of
      contraceptive use among women having undergone solid organ transplantation.
      RESULTS: From 643 articles, eight articles from seven studies satisfied review
      inclusion criteria; six articles pertained to kidney transplant patients, and two
      reported on liver transplant patients. Two reports of one prospective cohort of
      36 kidney transplant recipients taking combined oral contraceptives (COCs) or
      using the transdermal contraceptive patch reported no significant changes in
      biochemical measures after 18 months of use for either group, although 13 women
      modified antihypertensive medication, and two women discontinued the study
      because of serious medical complications. Four case reports of five kidney
      recipients using intrauterine devices reported inconsistent findings, including
      both beneficial health effects and contraceptive failures. One retrospective,
      noncomparative study of 15 liver transplant recipients using COCs or the
      transdermal contraceptive patch found no significant changes in any biochemical
      measures obtained, no discontinuations or severe complications and no pregnancies
      after a 12-month follow up. One case report of a liver transplant recipient on
      cyclosporine and prednisone documented the development of cholestasis associated
      with high-dose (50 mcg ethinyl estradiol) COC use as treatment for heavy uterine
      bleeding. CONCLUSIONS: Very limited evidence on COC and transdermal contraceptive
      patch use among kidney and liver transplant recipients indicated no pregnancies
      and no overall changes in biochemical measures. Excluding case reports, evidence
      on other contraceptive methods or contraception among other types of solid organ
      transplants was not identified.

PMID- 20682149
TI  - Guidance on medical eligibility criteria for contraceptive use: identification of
      research gaps.

PMID- 20682152
TI  - Vena cava filters: current concepts and controversies for the surgeon.

PMID- 20682153
TI  - Pathogenicity of amoebae.

PMID- 20682154
TI  - General anesthesia versus spinal anesthesia for laparoscopic cholecystectomy.
AB  - BACKGROUND AND OBJECTIVES: Laparoscopic cholecystectomy is the treatment of
      choice for cholelithiasis. The objective of this study was to compare the
      possibility of performing laparoscopic cholecystectomy under spinal anesthesia
      versus general anesthesia. METHODS: Between July 2007 and September 2008, 68
      patients with symptoms of cholelithiasis were included in this study. Patients
      with physical status ASA I and II were randomly divided to undergo laparoscopic
      cholecystectomy with low-tension pneumoperitoneum with CO(2) under general
      anesthesia (n = 33) or spinal anesthesia (n = 35). Propofol, fentanyl,
      rocuronium, sevoflurane, and tracheal intubation were used for general
      anesthesia. Hyperbaric bupivacaine 15 mg, and fentanyl 20 microg to achieve a
      sensorial level of T(3) were used for the spinal anesthesia. Intraoperative
      parameters, postoperative pain, complications, recovery, patient satisfaction,
      and cost were compared between both groups. RESULTS: All surgical procedures were
      completed with the chosen method and spinal anesthesia was converted to general
      anesthesia only in one patient. Pain was significantly lower at 2, 4, and 6 hours
      after the procedure under spinal anesthesia. The cost of the spinal anesthesia
      was significantly lower than that of the general anesthesia. All patients were
      discharged after 24 hours. In the postoperative evaluation, all patients were
      satisfied with the spinal anesthesia and would recommend this procedure.
      CONCLUSIONS: Laparoscopic cholecystectomy with low-pressure pneumoperitoneum with
      CO(2) can be safely performed under spinal anesthesia. Spinal anesthesia was
      associated with an extremely low level of postoperative pain, better recovery,
      and lower cost than general anesthesia.

PMID- 20682155
TI  - Evaluation of the influence of the codon 16 polymorphism of the Beta-2 adrenergic
      receptor gene on the incidence of arterial hypotension and ephedrine use in
      pregnant patients submitted to subarachnoid anesthesia.
AB  - BACKGROUND AND OBJECTIVES: The beta-2 adrenergic receptor gene has several
      polymorphisms. Recent studies have demonstrated the clinical importance of the
      latter. The objective of the present study was to evaluate the influence of the
      Arg16Gli polymorphism on the incidence of arterial hypotension and ephedrine use
      in pregnant patients submitted to subarachnoid block for Cesarean section.
      METHOD: Healthy parturients (ASA I and II) were submitted to subarachnoid
      anesthesia for elective Cesarean section (n = 50). Ephedrine was administered in
      cases of arterial hypotension. The incidence of arterial hypotension and the
      required dose of ephedrine to correct the arterial pressure were compared between
      the different genotypes identified. RESULTS: The most prevalent genotype was
      Arg16Gli (60%, n = 30) followed by Gli16Gli (26%, n = 13) and Arg16Arg (14%, n =
      7). No differences were observed regarding the basic characteristics of the
      genotypes. In comparison to the Arg16Arg genotype, the Gli16Gli presented a 3.95
      fold increase in the hazard ratio of arterial hypotension (95%CI 0.86-18.11; p =
      0.076), whereas the Arg16Gli presented a 4.83-fold increase (95%CI 1.13-20.50; p
      = 0.033). The parturients with the Arg16Arg needed, on average, 6.4 +/- 8.5 mg of
      ephedrine to correct the arterial hypotension, whereas those with the Arg16Gli
      needed 19.5 +/- 15.9 mg (p = 0.0445; 95%CI 0.3325-25.78) and the ones with the
      Gli16Gli genotype, 19.2 +/- 14.3 (p = 0.0445, 95%CI 0.3476-25.26). CONCLUSIONS:
      The results show that the genetic variant Arg16Arg presents a lower incidence of
      arterial hypertension and that lower doses of ephedrine were necessary to
      reestablish normal arterial pressure in the patients with this genetic profile.
      We conclude that the Arg16Arg genotype confers better pressure stability to the
      parturients submitted to subarachnoid anesthesia for Cesarean section.

PMID- 20682156
TI  - Comparison of the effects of dobutamine and milrinone on hemodynamic parameters
      and oxygen supply in patients undergoing cardiac surgery with low cardiac output
      after anesthetic induction.
AB  - BACKGROUND AND OBJECTIVES: Several classes of inotropic drugs with different
      hemodynamic effects are used in the treatment of low cardiac output in patients
      with diastolic dysfunction undergoing cardiac surgery. The objective of the
      present study was to compare the effects of dobutamine and milrinone on
      hemodynamic parameters and oxygen supply in this population of patients. METHODS:
      After approval by the Ethics Committee of the institution and signing of the
      informed consent, 20 patients undergoing cardiac surgery with cardiac index < 2
      L*min(-1)*m(2) after anesthetic induction and placement of a pulmonary artery
      catheter were randomly divided to receive dobutamine 5 microg*kg(-1). min(-1) (n
      = 10), or milrinone 0.5 microg*kg(-1)*min(-1) (n = 10). Hemodynamic parameters
      were measured after anesthetic induction and after 30 and 60 minutes, and
      arterial and venous blood gases were measured at baseline and 60 minutes. Non
      paired Student t test or two-way ANOVA for repeated measurements was used to
      compare the data. RESULTS: Dobutamine and milrinone promoted significant
      increases in cardiac index (56% and 47%) and oxygen supply (53% and 45%), and
      reduction in systemic (33% and 36%) and pulmonary (34% and 19%) vascular
      resistance, respectively. However, statistically significant differences were not
      observed between both drugs. CONCLUSIONS: Both inotropic drugs were similarly
      effective in restoring tissue blood flow and oxygen supply to adequate levels in
      patients with low cardiac output undergoing cardiac surgery.

PMID- 20682157
TI  - Assessing the impact of lung hyperinflation maneuver on systemic inflammatory
      response and lung collapse in patients undergoing surgeries under spontaneous
      ventilation.
AB  - BACKGROUND AND OBJECTIVES: Lung hyperinflation maneuvers (LHM) reverse
      intraoperative atelectasis; however, they can lead to pulmonary-induced systemic
      inflammatory response. The objective of this study was to determine the impact of
      LHM on systemic inflammatory response and lung structure in patients undergoing
      subarachnoid block. METHODS: After approval by the Ethics Committee of the
      institution and signing the informed consent, 20 patients undergoing small and
      medium surgical procedures were randomly separated into two groups: 1) control
      (CG), and 2) LHM (LHMG). One hour after the spinal anesthesia, LHM was performed
      in LHMG by applying bilevel positive pressure in the airways (BIPAP) with an
      expiratory pressure of 20 cmH(2)O and inspiratory pressure of 20 cmH(2)O for 1 to
      2 minutes. Blood levels of TNFalpha, IL-1, IL-6, IL-8, IL-10, and IL-12 were
      determined by flow cytometry at baseline and at 90, 180, and 780 minutes. Lung
      volumes and weights were determined using CT scans obtained immediately after the
      surgery. RESULTS: The use of LHM resulted in a reduction in the fraction of non
      aerated pulmonary parenchyma (7.5 +/- 4.3%, in the Control Group, vs. 4 +/- 2.1%,
      in the LHM Group, p = 0.02) without changing pulmonary volumes. A progressive
      increase in plasma levels of IL-1, IL-6, IL-8, and IL-10, similar in both groups,
      was observed. Plasma levels of TNFalpha and IL-12 were undetectable during the
      study. CONCLUSIONS: The use of LHM reduced the incidence of atelectasis, but it
      did not amplify the inflammatory response in patients with normal lungs
      undergoing small and medium surgeries under subarachnoid block.

PMID- 20682158
TI  - Effect of isolated anticonvulsant drug use and associated to midazolam as pre
      anesthetic medication on the Bispectral Index (BIS) in patients with cerebral
      palsy.
AB  - BACKGROUND AND OBJECTIVES: Patients with cerebral palsy (CP) frequently receive
      drugs for the treatment of concomitant diseases, such as seizures. Midazolam is a
      benzodiazepine with hypnotic action most often used as pre-anesthetic medication
      and its drug interactions in patients with CP are unknown. The objective of the
      present study was to evaluate the effect of midazolam as pre-anesthetic drug on
      the BIS of patients with CP undergoing chronic treatment with anticonvulsant
      agents. METHOD: Three groups of patients were assessed: CP without anticonvulsant
      treatment, CP undergoing treatment with anticonvulsant and a group with no
      disease and no medication use (control group). On the day before the surgery,
      with the patients conscious and in dorsal decubitus, the BIS monitor was placed
      and the basal BIS values were recorded. On the following day, 40 minutes before
      the surgery, the patients received 0.6 mg*kg(-1) of midazolam orally. Before the
      start of the anesthetic procedure, the same procedure for BIS recording was
      carried out after midazolam administration. RESULTS: A total of 107 patients were
      studied - 39 patients from the Control Group (CG) and 68 with a diagnosis of CP.
      Among these, 17 used anticonvulsant drugs. Regarding the mean BIS value after the
      midazolam administration, there was no difference between patients from the CG
      and those in the CP group that did not take anticonvulsant drugs, whereas the
      ones who took anticonvulsants exhibited a difference (p = 0.003). The possibility
      of decrease in the BIS after midazolam use increases according to the number of
      anticonvulsant drugs used by the patient. CONCLUSIONS: The chronic use of
      anticonvulsants associated to oral midazolam as pre-anesthetic medication can
      lead to the decrease in the BIS values, which configures deep level of hypnosis.

PMID- 20682159
TI  - Quality of life and mortality assessment in patients with major cardiac events in
      the postoperative period.
AB  - BACKGROUND AND OBJECTIVES: Cardiovascular complications in the postoperative
      period are associated with high mortality and morbidity. Few studies have
      assessed the degree of dependence in these patients and their perception of
      health. The objective of this study was to assess the mortality and the quality
      of life in patients who developed major cardiac events (MCE) in the postoperative
      period. METHOD: Retrospective study carried out in a Surgical Intensive Care Unit
      (SICU), between March 2006 and March 2008. The patients were assessed regarding
      the occurrence of CE. Six months after the hospital discharge, the Short-Form-36
      (SF-36) questionnaire was filled out and dependence was assessed in relation to
      activities of daily living (ADL). The comparisons between independent groups of
      patients were carried out using Student's t test. The comparison between each
      variable and the occurrence of CE was carried out by logistic regression and
      included all patients. RESULTS: Of the 1,280 patients that met the inclusion
      criteria, 26 (2%) developed MCE. The univariate analysis identified as
      independent determinants for the development of major cardiac events: ASA
      physical status, hypertension, ischemic heart disease, congestive heart disease
      and score of the Revised Cardiac Risk Index (RCRI). The six-month mortality after
      the SICU discharge was 35%. Of the 17 surviving patients, 13 completed the
      questionnaires. Thirty-one percent of them reported that their general health was
      better on the day they answered the questionnaire, when compared to 12 months
      before. Sixty-nine percent of the patients were dependent in instrumental ADL e
      15% in personal ADL. CONCLUSIONS: The development of MCE has a significant impact
      on the duration of hospital stay and mortality rates. Six months after the
      discharge from the SICU, more than 50% of the patients were dependent in at least
      one instrumental ADL.

PMID- 20682160
TI  - Evaluation of a computerized anesthesia report.
AB  - BACKGROUND AND OBJECTIVES: In Brazil, the use of information systems that allows
      filling out anesthesia reports automatically is still in its initial stages. The
      objective of this study was to validate an automated anesthesia record. METHODS:
      This study was approved by the Ethics Commission of the institution; an industry
      university partnership (Dixtal, Sao Paulo, Brazil and Universidade de Sao Paulo)
      was developed, and the study received a grant from FINEP (Financiadora de Estudos
      e Projetos do Ministerio de Ciencia e Tecnologia). The integration of hospital
      information systems for recovery of data regarding identification, preoperative
      evaluation, and laboratorial exams was the premise of this study. The
      applicability of the final version of the prototype of the automated system was
      evaluated by applying a semi-structured tool to 33 physicians, residents, and/or
      anesthesiologists during surgery procedures in 66 patients. Descriptive
      evaluation of the data was undertaken. RESULTS: The computerized system was
      considered reliable even for large surgeries by 81% of the participants. The
      majority of the anesthesiologists considered the prototype of great value for
      future studies and capable of meeting the requirements of anesthesia reports,
      bringing benefits for anesthesiologists, patients, and hospitals. The full use of
      the system requires training and some of its aspects can be improved.
      CONCLUSIONS: Validation of this prototype of a computerized system for
      elaboration of anesthesia reports showed the viability of this type of solution
      to help anesthesiologists in their daily tasks, increasing the reliability of the
      data. Besides, when evaluating the applicability, anesthesiologists considered
      that the prototype could be useful for patients, physicians, and hospitals.

PMID- 20682161
TI  - Influence of naloxone and methysergide on the analgesic effects of low-level
      laser in an experimental pain model.
AB  - BACKGROUND AND OBJECTIVES: Although the mechanism of action of laser phototherapy
      (LPT) is not known, it is a promising analgesic method. The aim of this study was
      to evaluate whether the action of LPT depends on the activation of peripheral
      opioid or serotonergic receptors. METHOD: Inflammatory pain was induced through
      the injection of carrageenin in the left posterior paw of male Wistar rats. The
      InGaAIP visible laser diode (660 nm) with fluency of 2.5 J*cm(-2) was used. Von
      Frey filaments were used to analyze mechanical hyperalgesia. Animals were
      separated into five groups: Carrageenin; Laser (LPT); Non-coherent light; LPT +
      Naloxone; and LPT + Methysergide. RESULTS: Low-Level Laser phototherapy proved to
      be an effective analgesic method, while non-coherent light did not show a similar
      effect. The use of naloxone blocked the analgesic effect of LPT, while
      methysergide did not affect LPT-induced analgesia. CONCLUSIONS: According to the
      parameter used in this study, LPT produced analgesia. Analgesia induced by laser
      phototherapy is mediated by peripheral opioid receptors. Laser phototherapy does
      not seem to interact with peripheral serotonergic receptors.

PMID- 20682162
TI  - Anesthesia for emergency separation of omphalopagus conjoined twins.
AB  - BACKGROUND AND OBJECTIVES: The rate of mortality during the surgical separation
      of conjoined twins in the neonatal period is 50% and can reach up to 75% if it
      occurs in emergency situations. The planning of the surgical separation procedure
      is detailed and involves imaging assessment, evaluation of cross-circulation and
      even other surgical preparation procedures, such as skin expansion. CASE REPORT:
      Eleven-day-old female omphalopagus conjoined twins underwent emergency surgical
      separation due to the death of one twin caused by sepsis associated to
      cardiopathy. The liver was shared by the twins and was separated. The surviving
      twin died six days later. CONCLUSIONS: Surgical separation of conjoined twins in
      the neonatal period must be avoided due to the patients' organic system
      immaturity. However, emergency situations such as the one described herein can
      require the procedure to be carried out.

PMID- 20682163
TI  - Anesthesia for tonsillectomy in a child with Klippel-Feil Syndrome associated
      with Down Syndrome. Case report.
AB  - BACKGROUND AND OBJECTIVES: Craniofacial abnormalities present in Klippel-Feil
      Syndrome (KFS) and Down Syndrome (DS) can hinder access to the airways.
      Oropharyngeal surgeries also require special attention with the airways. The
      association of both syndromes in a patient scheduled for tonsillectomy is a rare
      condition that imposes challenges to the anesthetic-surgical treatment. The
      objective of this report was to discuss the approach of the airways and the risks
      of cervical manipulation in a patient with KFS and DS undergoing tonsillectomy.
      CASE REPORT: This is a 5 years old child with diagnosis of KFS and DS and
      instability of the atlantoaxial joint who underwent tonsillectomy under general
      balanced anesthesia. Ventilation under face mask and tracheal intubation were
      done with the neck in the neutral position. The perfect visualization of the
      epiglottis and vocal cords allowed tracheal intubation with conventional
      laryngoscopy. The surgery was also performed without cervical extension and
      without intercurrences. CONCLUSIONS: Although access to the airways can be easy,
      anatomical changes presuppose the presence of difficult airways in patients with
      KFS and DS. Differentiated care and adequate resources are mandatory to avoid
      complications during approach of the airways. Cervical manipulation should be
      avoided in the presence of instability of the atlantoaxial joint due to the risk
      of neurological damage.

PMID- 20682164
TI  - Osteogenesis imperfecta in pregnancy. Case report.
AB  - BACKGROUND AND OBJECTIVES: Osteogenesis Imperfecta is a rare condition,
      especially in obstetric patients. It has an estimated prevalence of 1/10,000 in
      the general population, and 1/25,000 to 30,000 in obstetric patients. The
      objective of this report was to present a rare case of a pregnant woman with
      Osteogenesis Imperfecta undergoing cesarean section. CASE REPORT: This is a 23
      years old gravida on the 38th week, admitted to the maternity ward with loss of
      amniotic fluid and contractions for four hours, associated with the absence of
      fetal movements for four days. The patient had a mild form of Osteogenesis
      Imperfecta without other comorbidities. She was not taking any medication, and
      she did not have prenatal follow-up. The patient underwent spinal anesthesia in
      the L(3)-L(4) space, median approach, with a single puncture with a 27G Quincke
      needle and the administration of hyperbaric 0.5% bupivacaine (10 mg) and morphine
      (60 microg). She was discharged in the second postoperative day without
      complaints. CONCLUSIONS: Fertility is preserved, especially in those patients
      with type I of the disease, and pregnancy can be carried to term. Delivery is
      usually surgical due to pelvic deformities in the gravida, cephalopelvic
      disproportion, and increased incidence of abnormal fetal presentation. The
      importance of the anesthesiologist in the surgical team relies on the
      perioperative management and the choice of the most appropriate anesthetic
      technique for each patient.

PMID- 20682165
TI  - Intraoperative intravenous lidocaine.
AB  - BACKGROUND AND OBJECTIVES: Most patients undergoing surgery experience moderate
      to severe pain, indicating the need to improve the anesthetic technique.
      Intravenous lidocaine has been widely used in the treatment of chronic pain. The
      objective of this report was to review the use of intravenous lidocaine for
      postoperative analgesia. CONTENTS: The pharmacologic aspects and mechanism of
      action of lidocaine as well as clinical studies in which the authors used
      intraoperative lidocaine were reviewed. CONCLUSIONS: Intravenous lidocaine can
      promote analgesia in surgical procedures, representing another alternative for
      the treatment of acute pain. Controlled studies with different surgical
      interventions could bring more information on this modality of analgesia.

PMID- 20682166
TI  - Remifentanil as analgesia for labor.
AB  - BACKGROUND AND OBJECTIVES: The neuraxial techniques currently represent the most
      effective methods for pain control during labor and the epidural block using
      ultradiluted anesthetic solutions is considered the gold standard promoting
      adequate pain relief with minimum side effects. In some situations however the
      use of these techniques is limited by the existence of maternal
      contraindications, or structural or material obstacles. In these cases, the
      alternatives are still precarious and scarce offering little optimistic results
      and of dubious effectiveness. CONTENT: This article presents through a literature
      review the available information on the use of remifentanil as an alternative
      technique for analgesia during labor discussing aspects of pharmacokinetics,
      analgesia efficacy, maternal satisfaction and maternal/fetal side effects.
      CONCLUSIONS: The initial data show that remifentanil is a promising option to be
      employed in situations where the parturient cannot or does not want to receive
      the neuraxial analgesia.

PMID- 20682167
TI  - Non-arteritic anterior ischemic optic neuropathy: role of systemic corticosteroid
      therapy.

PMID- 20682168
TI  - The patient's perspective (dilation is dilatory).

PMID- 20682169
TI  - Acute pulmonary embolism. Foreword.

PMID- 20682170
TI  - Acute pulmonary embolism.
AB  - Most large or fatal pulmonary embolisms (PE) at autopsy were unsuspected ante
      mortem. Newly identified clinical characteristics of PE enhance our ability to
      identify potential patients. Because of laudable efforts to diagnose PE, about
      90% of outpatient computed tomographic (CT) angiograms are negative. Overuse of
      CT angiography has resulted in huge expenses and exposure of many to radiation.
      Approximately 30% of patients with suspected acute PE would not need imaging if D
      dimer is normal and clinical assessment is not a high probability, but such
      triage is uncommonly used. Perhaps perfusion imaging should be used more
      frequently. Radiation and cost with scintigraphy are less than with CT
      angiography. Single-photon emission computed tomography lung scans appear to be
      more effective than planar lung scans. Diseases associated with an increased risk
      of PE are being identified, but recommended prophylaxis usually is not given.
      Potential benefits and risks of treatment options need to be assessed.

PMID- 20682171
TI  - Comparison of bioartificial pancreas performance in the bone marrow cavity and
      intramuscular space.
AB  - BACKGROUND AND AIMS: Bone marrow with a widely distributed and well-vascularized
      microenvironment that is capable of sustaining grafts is a potential site for
      islet transplantation. The femur bone marrow cavity offers sufficient space that
      may also receive the implantation of bioartificial pancreas (BAP). METHODS: Mouse
      insulinoma cells encapsulating in agarose gel were further enclosed in a calcium
      phosphate cement chamber to create a BAP. BAPs implanted into the femur bone
      marrow cavity of diabetics were compared with those implanted in the
      intramuscular space. Blood glucose level and C-peptide were determined
      perioperatively. RESULTS: The blood glucose level of the diabetics receiving BAPs
      in the intramuscular space decreased from 413 +/- 24 to 285 +/- 47 mg/dL at 1 day
      post-surgery. However, the blood glucose level returned to 398 +/- 35 mg/dL with
      undetectable serum C-peptide at 2 weeks postoperatively that reveals implant
      failure. The blood glucose level of diabetics receiving BAPs into the femur bone
      marrow cavity decreased from 422 +/- 32 to 247 +/- 52 mg/dL and maintained in the
      range of 288 +/- 47 mg/dL during the experimental period with an increase in C
      peptide level from 6.1 +/- 2.8 to 104.7 +/- 16.4 pmol/L. CONCLUSIONS: This
      preliminary study indicates that the effectiveness of BAPs transplanted into the
      femur bone marrow cavity is superior to that implanted in the intramuscular
      space, which reveals the bone marrow may be a potential receptor site for the BAP
      transplantation.

PMID- 20682172
TI  - In vitro modulation of peroxisome proliferator-activated receptor-gamma and its
      genes by C-reactive protein. Role of atorvastatin.
AB  - BACKGROUND AND AIMS: C-reactive protein (CRP) serves not only as a biomarker for
      the risk of cardiovascular disease and underlying inflammation but also functions
      as an active mediator of atherosclerosis by promoting activation of endothelial
      cells and monocytes. Peroxisome proliferator activated receptor-gamma (PPAR
      gamma) transcription factor has been recognized to regulate the expression of
      many genes involved in inflammation, lipid metabolism and vascular remodeling.
      Therefore, in the present study we tried to explore the role of CRP as a possible
      mediator of atherosclerosis by determining its effect on PPAR-gamma and its
      effector genes, i.e., liver X receptor-alpha (LXR-alpha) and matrix
      metalloproteinase-9 (MMP-9) in THP-1 cells. METHODS: Semi-quantitative RT-PCR was
      used to determine mRNA expression. RESULTS: CRP upregulates the expression of
      PPAR-gamma and LXR-alpha at lower doses (5-25 microg/mL), which were further
      declined at higher doses (50-100 microg/mL). However, a dose-dependent increase
      was observed for MMP-9 expression. Atorvastatin (10-20 microM) was able to
      significantly accelerate the CRP-induced expression of PPAR-gamma and LXR-alpha
      and attenuate MMP-9 expression. CONCLUSIONS: For the first time we demonstrate
      that CRP modulates PPAR-gamma and its effector genes and reinforces the
      mechanistic link of CRP as a possible mediator in atherosclerosis and also
      advocate atorvastatin as a therapeutic modality.

PMID- 20682173
TI  - Sensitization of osteosarcoma cell line SaOS-2 to chemotherapy by downregulating
      survivin.
AB  - BACKGROUND AND AIMS: Osteosarcoma is the most frequent malignant bone tumor with
      a peak incidence in the second and third decades of life. Survivin, a member of
      the IAP family of proteins, is overexpressed in osteosarcomas and plays an
      important role in protecting cells from apoptosis. Here we investigated the anti
      cancer effects of downregulating survivin by shRNA vector pSUPER-sh in
      combination with chemotherapeutic drugs on human osteosarcoma cells. METHODS:
      Expression of survivin was detected by Western blot. The effects of pSUPER-sh and
      chemotherapeutic drugs on osteosarcoma cell lines Saos-2 and U2OS by cell
      viability assay and its underlying mechanisms were analyzed by flow cytometry and
      caspase-3 activity assay. RESULTS: Downregulated survivin could significantly
      induce apoptosis of osteosarcoma cell lines Saos-2 and U2OS. The effect probably
      resulted from downregulation of survivin induced by pSUPER-sh. Importantly, we
      found that the downregulation of survivin by pSUPER-sh could enhance the
      anticancer effects of chemotherapies such as etoposide, cisplatin and doxorubicin
      through decreasing mitochondrial membrane potentials and increasing caspase-3
      activity. CONCLUSIONS: Downregulated survivin by pSUPER-sh could markedly induce
      apoptosis of osteosarcoma cells lines and pSUPER-sh may be a promising adjuvant
      in osteosarcoma chemotherapy.

PMID- 20682174
TI  - Actin cytoskeleton participation in the onset of IL-1beta induction of an
      invasive mesenchymal-like phenotype in epithelial MCF-7 cells.
AB  - BACKGROUND: Interleukin 1 beta (IL-1beta) and other inflammatory cytokines are
      reported to induce phenotypic changes in epithelial breast cancer tumor cells
      related to increased invasiveness. Mechanisms involved in the process are not
      well understood. METHODS: The noninvasive breast cancer epithelial cell line MCF
      7 was used to investigate the IL-1beta-induced phenotype. Live cells expressing
      EGFP-actin were monitored for cell morphology changes and actin cytoskeleton
      dynamics by time-lapse video microscopy in the presence of IL-1beta and specific
      inhibitors of actin signaling pathways. Chemotaxis, invasion of Matrigel, MMP
      activity and expression of S100A4 in cells treated with IL-1beta were assessed by
      migration assays, zymograms and immunoblots. RESULTS: Exposure to IL-1beta
      specifically induced a change in MCF-7 cells from a typical epithelial morphology
      into elongated cells, showing numerous dynamic actin-rich lamellae and peripheral
      ruffles characteristic of fibroblasts. These cells could scatter from compact
      cell colonies and respond to chemoattractants such as the homing-associated
      chemokine CXCL-12. Pharmacological blockage of actin signaling pathways and
      negative mutants of RhoGTPases revealed that actin reorganization and enhanced
      motility are regulated via PI3K/Rac 1 activation. IL-1beta-stimulated cells
      expressed the metastasis promoter S100A4, increased secretion of active MMP-9 and
      MMP-2 and invasion of extracellular matrix proteins. CONCLUSIONS: IL-1beta
      induces a PI3K/Rac 1-regulated reorganization of the actin cytoskeleton of MCF-7
      cells that is required for cell scattering, elongation and migration. The
      enhanced motility is accompanied by expression of protein markers correlated with
      invasive behavior.

PMID- 20682175
TI  - Elevated serum level of IL-23 correlates with expression of VEGF in human
      colorectal carcinoma.
AB  - BACKGROUND AND AIMS: Interleukin-23 (IL-23) has a role in inflammatory bowel
      diseases (IBD) as a condition of higher risk of colorectal carcinogenesis.
      Vascular endothelial growth factor (VEGF) is overexpressed in IBD and colorectal
      carcinoma. Therefore, we aimed at uncovering the relationship between serum level
      of IL-23 and expression of VEGF in colorectal cancer (CRC) patients and to
      establish the relationship between VEGF and p53 and serum levels of IL-23, as
      well as its possible role in carcinogenesis of colorectal carcinomas. METHODS:
      Levels of IL-23 from serum samples of patients with colorectal carcinoma (n = 40)
      and healthy control samples (n = 37) were examined for IL-23-Ab using an ELISA
      assay. We also determined the expression of VEGF and p53 by immunohistochemistry
      in 59 cases of CRC. RESULTS: We found significantly higher serum levels of IL-23
      in patients with CRC compared to control subjects (IL-23; mean 189.46 pg/mL vs.
      mean 34.77 pg/mL, p = 0.033). We also detected higher serum levels of IL-23 in
      patients with overexpressed VEGF (p = 0.028). Our results also showed that
      concomitant expression of VEGF and increased serum levels of IL-23 are in
      positive correlation with histological grade 2 (p <0.05). CONCLUSIONS: Our data
      indicate that serum IL-23 levels are significantly elevated in CRC vs. control
      patients and are strongly associated with overexpression of VEGF, thus they may
      play an important role in carcinogenesis of CRC.

PMID- 20682176
TI  - Decreased 1-25 dihydroxyvitamin D3 concentration in peripheral blood serum of
      patients with thyroid cancer.
AB  - BACKGROUND AND AIMS: Vitamin D(3), in addition to its role in calcium
      homeostasis, has been recognized as playing a role in human cancer development.
      However, little is known about the association between vitamin D status and the
      development of thyroid cancer. This study aimed to investigate vitamin D
      metabolism by measuring 25(OH) D(3), 1-25 (OH)(2) D(3), PTH and calcium
      concentrations in the peripheral blood of patients with different forms of
      thyroid tumors. METHODS: The 25-hydroxyvitamin D(3) ,1-25- dihydoxyvitamin D(3),
      PTH and calcium serum levels of 50 consecutive patients with epithelial thyroid
      cancer 27 cases of papillary cancers (PTC), 16 follicular cancers (FTC), and
      seven cases of anaplastic cancers (ATC) and 34 multinodular nontoxic goiter (MNG)
      were measured by specific immunoassay. The control group consisted of 26 healthy
      volunteers. RESULTS: Our results revealed significantly lower 1-25 (OH)(2) D(3)
      concentration in the PTC group (22.67 pg/mL +/- 8.12; p <0.05), FTC group (16.09
      pg/mL +/- 6.15; p <0.02) and ATC group (9.48 pg/mL +/- 5.18; p <0.02). Levels of
      1-25 (OH)(2) D(3) varied by cancer stage and were also significantly different. A
      significant decrease in circulating 1-25 (OH)(2) D(3) concentration was found in
      patients with stage I (24.12 pg/mL +/- 6.77; p <0.05), stage II (16.93 pg/mL +/-
      4.55; p <0.05), stage III (12.44 +/- 8.98; p <0.02) and in stage IVa (6.18 +/-
      2.22; p <0.01). There were no significant differences when comparing serum levels
      of 25(OH) D(3), PTH or calcium concentrations among individuals with multinodular
      goiter, thyroid cancer and age- and sex-matched control volunteers. CONCLUSIONS:
      Our study revealed that impaired vitamin D(3) metabolism may play an important
      role in thyroid follicular cell oncogenesis.

PMID- 20682177
TI  - Expression of two testis-specific genes, SPATA19 and LEMD1, in prostate cancer.
AB  - BACKGROUND AND AIMS: Screening methods for early detection of prostate cancer
      have some limitations regarding specificity and sensitivity, so there is a
      continuing search to find new cancer biomarkers. Cancer-testis genes are a group
      of genes with expression almost limited to testis and different kinds of tumors.
      Since testis is an immune privileged site, if these genes are expressed in
      tumors, they can be immunogenic. We undertook this study to find new members of
      the cancer-testis gene family appropriate for cancer immunotherapy METHODS: We
      analyzed the expression of six testis-specific genes called ODF1, ODF2, ODF3,
      ODF4, LEMD1 and SPATA19 in 30 prostate cancer and 25 benign prostate hyperplasia
      (BPH) samples by RT-PCR and restriction fragment length polymorphism (RFLP).
      RESULTS: Of the prostate cancer samples, 10, 10, 23 and 40% showed ODF1, ODF2,
      LEMD1 and SPATA19 specific bands, respectively, but none of the BPH samples
      expressed any of these genes. The difference between prostate cancer and BPH
      groups for LEMD1 and SPATA19 expression was significant. Mean serum PSA level was
      significantly higher in patients expressing ODF2 than in the other patients.
      CONCLUSIONS: ODF1, ODF2, SPATA19 and LEMD1 are members of cancer-testis gene
      family. In addition, LEMD1 and SPATA19 are putative cancer biomarkers and
      promising targets for active immunotherapy.

PMID- 20682178
TI  - Negative association of c-fos expression as a favorable prognostic indicator in
      gastric cancer.
AB  - BACKGROUND AND AIMS: The onco-protein c-fos was previously linked to favorable
      prognosis of gastric cancer (GC) without further validations. The present study
      was designed to address the issue based on a cohort of Chinese patients. METHODS:
      Expression of c-fos was determined by immunohistochemical staining in specimens
      from 58 patients with GC who underwent surgical resection. The relationships
      between c-fos expression and clinicopathological and prognostic variables were
      further evaluated. RESULTS: Expression of c-fos in tumor epithelia was observed
      in 39 (67.2%) patients. The protein was also positively expressed in lymphocytes
      within tumors and para-tumor epithelia. Tumors with positive expression of c-fos
      in tumor epithelia had a smaller size and marginally earlier T stage in all
      patients and/or those who underwent curative resection. Univariate analysis
      showed that patients with positive c-fos expression in tumor epithelia had
      significantly prolonged overall and tumor-free survival. Cox regression analysis
      revealed that c-fos expression in tumor epithelia was an independent or potential
      independent indicator of improved prognosis in different subgroups of patients.
      Expression of c-fos in para-tumor epithelia and intra-tumor lymphocytes was not
      associated with clinicopathological variables and long-term outcomes in patients.
      CONCLUSIONS: Our data demonstrated that c-fos expression was negatively
      associated with tumor progression and was predictive for favorable survival in
      patients with GC.

PMID- 20682179
TI  - Two novel mutations in SCN1A gene in Iranian patients with epilepsy.
AB  - BACKGROUND AND AIMS: Epilepsy as a common chronic neurological disorder is
      characterized by recurrent unprovoked seizures. Febrile seizures are the most
      common type of epilepsy in infants and children. Our aim was the molecular
      analysis of SCN1A gene in affected Iranian patients with GEFS+ and Dravet
      syndrome diagnosed clinically to explain genotype-phenotype correlation and exact
      classification. METHODS: The 34 unrelated Iranian families with epilepsy were
      selected and screened for SCN1A mutations by MLPA, ARMS, and PCR-RFLP confirmed
      by direct sequencing. RESULTS: MLPA analysis showed normal patterns, but direct
      sequencing revealed that generally 20/34 (0.588) probands have common reported
      single nucleotide polymorphisms (SNPs) (p.A1067G; rs2298771) with allelic
      frequency as 0.706/0.294 in patients and 0.515/0.485 in control group,
      respectively, for A/G. No significant differences between groups were observed.
      Moreover, four novel allelic variants as missense substitutions included two new
      sequence variation (p.F412 I, p.Y1274N) and two previously reported mutations
      (p.R101G, p.S103G) that were detected in 4/34 probands but not in control groups
      and other healthy normal family members. CONCLUSIONS: Clinical diagnosis could
      nearly establish the classification, but mutation screening helps clinicians to
      confirm their data. We found mutation in four probands and confirmed the net
      diagnosis. Our data suggest that the clinical symptom variations could be also
      explained, considering the role of modifier genes such as mitochondrial mutations
      or other genes responsible for drug metabolism pathways including multiple drug
      resistance family genes (ABCB1) or MTHFR.

PMID- 20682180
TI  - Polymorphisms in NAT2 gene and atherosclerosis in an Algerian population.
AB  - BACKGROUND AND AIMS: The etiology of atherosclerosis is multifactorial. Genetic
      and environmental factors are involved in the development of atherosclerosis.
      Human arylamine N-acetyltransferase 2 (NAT2) is an important metabolizing enzyme
      that exhibits genetic polymorphisms and modifies individual response and/or
      toxicity to many xenobiotics. We undertook this study to investigate the NAT2
      polymorphisms in patients with atherosclerosis. METHODS: Genotyping for NAT2
      alleles was performed using polymerase chain reaction-restriction fragment-length
      polymorphism (PCR-RFLP) in 285 Algerian patients with atherosclerosis and 286
      controls. RESULTS: There was no association between NAT2 polymorphisms and
      atherosclerosis risk. However, the haplotype NAT2(*)5F decreased susceptibility
      to the disease (p = 0.005, OR = 0.55, 95% CI = 0.37-0.84). The frequency of the
      slow acetylator phenotype was approximately 50% in both cases and controls.
      CONCLUSIONS: These results suggest that NAT2 polymorphisms may not be involved in
      the pathogenesis of atherosclerosis.

PMID- 20682181
TI  - IL-23: a promising therapeutic target for systemic lupus erythematosus.
AB  - Cytokine-mediated immunity plays a crucial role in the pathogenesis of various
      autoimmune diseases including systemic lupus erythematosus (SLE). The recent
      identification of the dimeric interleukin (IL)-12-related cytokine IL-23 now
      contributes to our understanding of the fine-tuning of cellular immunity. The
      critical implication of IL-12 p40 in autoimmune inflammation has long been
      misinterpreted and until recently have studies revealed that it is IL-23, not IL
      12, is the crucial factor in this immune dysregulation. Therefore, targeting of
      IL-23 or the IL-23 receptor is a potential therapeutic approach for autoimmune
      diseases including SLE. In this opinion article, we will discuss the biological
      features of IL-23 and summarize recent advances on the role of IL-23 in the
      pathogenesis and treatment of SLE.

PMID- 20682182
TI  - The revitalized tau hypothesis on Alzheimer's disease.
AB  - Many hypotheses have been raised regarding the pathophysiology of Alzheimer's
      disease (AD). Because amyloid beta peptide (Abeta) deposition in senile plaques
      appears as a late, nonspecific event, recent evidence points to tau
      phosphorylation and aggregation as the final common pathway in this
      multifactorial disease. Current approaches that provide evidence in favor of
      neuroimmunomodulation in AD and the roles of tau pathological modifications and
      aggregation into oligomers and filamentous forms are presented. We propose an
      integrative model on the pathogenesis of AD that includes several damage signals
      such as Abeta oligomers, oxygen free radicals, iron overload, homocysteine,
      cholesterol and LDL species. These activate microglia cells, releasing
      proinflammatory cytokines and producing neuronal degeneration and tau
      pathological modifications. Altered and aggregated forms of tau appear to act as
      a toxic stimuli contributing to neurodegeneration. Recent findings provide
      further support to the central role of tau in the pathogenesis of AD, so this
      protein has turned into a diagnostic and therapeutic target for this disease.

PMID- 20682183
TI  - Association of gamma-glutamyl transferase with cardiovascular risk: a prognostic
      outlook.

PMID- 20682185
TI  - The Edward Jenner Society: a new academic society for vaccinologists.

PMID- 20682186
TI  - Factors associated with complicated buprenorphine inductions.
AB  - Despite data supporting its efficacy, barriers to implementation of buprenorphine
      for office-based treatment are present. Complications can occur during
      buprenorphine inductions, yet few published studies have examined this phase of
      treatment. To examine factors associated with complications during buprenorphine
      induction, we conducted a retrospective chart review of the first 107 patients
      receiving buprenorphine treatment in an urban community health center. The
      primary outcome, defined as complicated induction (precipitated or protracted
      withdrawal), was observed in 18 (16.8%) patients. Complicated inductions were
      associated with poorer treatment retention (than routine inductions) and
      decreased over time. Factors independently associated with complicated inductions
      included recent use of prescribed methadone, recent benzodiazepine use, no prior
      experience with buprenorphine, and a low initial dose of buprenorphine/naloxone.
      Findings from this study and further investigation of patient characteristics and
      treatment characteristics associated with complicated inductions can help guide
      buprenorphine treatment strategies.

PMID- 20682187
TI  - Effectiveness of adding relapse prevention materials to telephone counseling.
AB  - The purpose of this study was to examine the effectiveness of adding the Forever
      Free relapse prevention materials to telephone counseling provided by the
      Arkansas quitline. Results suggest that the addition of Forever Free materials to
      telephone counseling does not improve quit rates for those participants who
      receive at least one session of counseling and nicotine patches; however, for
      those participants unwilling or unable to receive nicotine patches, the addition
      of the Forever Free relapse prevention materials doubled the abstinence rate and
      increased the odds of abstinence by nearly 70% 6 months after treatment (20.9%
      versus 10.6%; OR = 1.69; CI = 1.02-2.78; p = .04). Given the recent proliferation
      of quitline services and the variety of services provided, these results can
      address concerns about enhancing treatment outcomes for certain groups.

PMID- 20682188
TI  - Cortical perfusion in alcohol-dependent individuals during short-term abstinence:
      relationships to resumption of hazardous drinking after treatment.
AB  - Relapse to hazardous levels of alcohol consumption after treatment for alcohol
      use disorders is common. Investigation of the neurobiological correlates of
      resumption of hazardous drinking is necessary to clarify the mechanisms
      contributing to relapse. Fifty-seven treatment-seeking alcohol-dependent
      participants (ALC) completed arterial spin labeling perfusion MRI of the frontal
      and parietal gray matter (GM) at 7+/-3 days of abstinence (baseline). ALC
      participants were restudied after 35+/-11 days of abstinence (assessment point 2:
      AP2). Twenty-eight nonsmoking, light-drinking control participants (nsLD) from
      the community were studied with perfusion MRI. ALC participants were followed
      over 12 months after baseline study and were classified as abstainers (no alcohol
      consumption; n=19) and resumers (any alcohol consumption; n=38) at follow-up.
      Cross-sectional and longitudinal perfusion was compared in abstainers, resumers,
      and nsLD. At baseline, resumers demonstrated significantly lower frontal and
      parietal GM perfusion than nsLD and abstainers. Abstainers and nsLD were not
      different on frontal or parietal GM perfusion. No significant longitudinal
      perfusion changes were observed in abstainers and resumers. At AP2, resumers
      showed significantly lower frontal GM perfusion than nsLD and abstainers, whereas
      no group differences were observed for parietal GM. Abstainers and nsLD were not
      different on frontal GM perfusion. The significantly decreased frontal GM
      perfusion in resumers compared with both abstainers and nsLD across the
      assessment interval suggests premorbid and/or acquired neurobiological
      abnormalities of the frontal GM in resumers.

PMID- 20682189
TI  - Liver transplantation for end-stage alcoholic liver disease: a single-center
      experience from mainland China.
AB  - There has been a gradual increase in the number of patients with end-stage
      alcoholic liver disease (ALD) undergoing liver transplantation (LT) in mainland
      China. However, few studies have focused on the post-transplant outcomes of this
      population. The aim of this study was to evaluate the efficacy of LT in patients
      with ALD, mainly focusing on survival rates, complications, and alcohol
      recidivism. The results were retrospectively analyzed from 20 patients, who
      underwent LT for ALD from December 2003 to September 2007 at Liver Transplant
      Center of Third Affiliated Hospital of Sun Yat-sen University. The 1-, 2-, and 3
      year survival rates of the ALD group and non-ALD group were 90.0, 80.0, 80.0% and
      90.3, 84.7, 79.8%, respectively. There was no significant difference in 1-, 2-,
      and 3-year survival rates between these two groups (P=.909). No significant
      difference was observed in complications such as pulmonary infection (50.0 vs.
      31.9%, P=.137), biliary complications (15.0 vs. 27.4%, P=.297), hepatic arterial
      complications (10.0 vs. 6.9%, P=.641), and rejection (15.0 vs. 8.1%, P=.394)
      after LT between the ALD group and non-ALD group. There was only one person who
      resumed mild, intermittent drinking after LT. End-stage ALD is a good indication
      for LT, with similar results in non-ALD patients. The major cause of death in ALD
      patients after LT was infectious complications. More attention is needed for the
      prophylaxis of infectious complications after LT.

PMID- 20682190
TI  - Pattern of alcohol consumption and its effect on gastrointestinal symptoms in
      inflammatory bowel disease.
AB  - Alcohol consumption is a potential trigger for flare in inflammatory bowel
      disease (IBD) flare because of alcohol's pro-oxidant effects and its deleterious
      effects on gut barrier function. The association with alcohol consumption and IBD
      flare is unclear. To test this hypothesis, we evaluated the pattern of alcohol
      consumption and its self-reported effect on gastrointestinal (GI) symptoms in
      patients with IBD. We recruited 129 consecutive patients: 52 patients with
      Crohn's disease, 38 patients with ulcerative colitis, and 39 patients with
      irritable bowel syndrome (IBS). All the participants completed a validated
      questionnaire on disease activity (the Crohn's disease activity index or
      ulcerative colitis clinical activity index, respectively) validated
      questionnaires to quantify alcohol consumption by National Institute of Alcohol
      Abuse and Alcoholism criteria, and two structured questionnaires we designed to
      access patients' perception of the effect of alcohol on their GI symptoms and on
      overall GI symptom severity. The pattern of current, light, moderate, and heavy
      alcohol consumption in inactive IBD was similar to the general U.S. population.
      Specifically, of the 90 inactive IBD patients, 56 (62%) were current drinkers,
      compared with 61% in the general U.S. population. Of current drinkers, 75% of IBD
      (N=42) and 43% of IBS (N=9) reported a worsening of GI symptoms with alcohol
      consumption (P=.01); however, overall GI symptom severity did not differ when
      compared with quantity of alcohol consumed. Patients with inactive IBD drink
      alcohol in quantities similar to the general population. Current drinkers with
      inactive IBD are more likely to report worsening of GI symptoms with alcohol than
      current drinkers with IBS.

PMID- 20682191
TI  - Circadian wheel-running activity during withdrawal from chronic intermittent
      ethanol exposure in mice.
AB  - Alcohol withdrawal is associated with affective-behavioral disturbances in both
      human alcoholics and in animal models. In general, these phenomena are
      potentiated by increased alcohol exposure duration and by prior withdrawal
      episodes. Previous studies have also reported locomotor hypoactivity during
      ethanol withdrawal in rats and mice, but only in novel test environments and not
      in the home cage. In the present study, we examined the effects of withdrawal
      from chronic intermittent ethanol (CIE) vapor exposure on the level and circadian
      periodicity of wheel-running activity in C57BL/6J mice. CIE treatment resulted in
      reductions in wheel-running activity compared with plain-air controls that
      persisted for about 1 week after withdrawal. Analysis of circadian waveforms
      indicated that reduced activity occurred throughout the night phase, but that
      daily-activity patterns were otherwise unaltered. CIE failed to alter free
      running circadian period or phase in animals maintained under constant darkness.
      These results show that ethanol withdrawal can result in locomotor hypoactivity
      even in the habitual, home-cage environment, and suggest that withdrawal-related
      reductions in wheel-running activity may reflect the specific motivational
      significance of this behavior.

PMID- 20682192
TI  - Serotonin-3 receptors in the posterior ventral tegmental area regulate ethanol
      self-administration of alcohol-preferring (P) rats.
AB  - Several studies indicated the involvement of serotonin-3 ([5-hydroxy tryptamine]
      5-HT(3)) receptors in regulating alcohol-drinking behavior. The objective of this
      study was to determine the involvement of 5-HT(3) receptors within the ventral
      tegmental area (VTA) in regulating ethanol self-administration by alcohol
      preferring (P) rats. Standard two-lever operant chambers (Coulbourn Instruments,
      Allentown, PA) were used to examine the effects of seven consecutive bilateral
      microinfusions of ICS 205-930 (ICS), a 5-HT(3) receptor antagonist, directly into
      the posterior VTA on the acquisition and maintenance of 15% (vol/vol) ethanol
      self-administration. P rats readily acquired ethanol self-administration by the
      fourth session. The three highest doses (0.125, 0.25, and 1.25 microg) of ICS
      prevented acquisition of ethanol self-administration. During the acquisition
      postinjection period, all rats treated with ICS demonstrated higher responding on
      the ethanol lever, with the highest dose producing the greatest effect. In
      contrast, during the maintenance phase, the three highest doses (0.75, 1.0, and
      1.25 microg) of ICS significantly increased responding on the ethanol lever;
      after the 7-day dosing regimen, responding on the ethanol lever returned to
      control levels. Microinfusion of ICS into the posterior VTA did not alter the low
      responding on the water lever and did not alter saccharin (0.0125% wt/v) self
      administration. Microinfusion of ICS into the anterior VTA did not alter ethanol
      self-administration. Overall, the results of this study suggest that 5-HT(3)
      receptors in the posterior VTA of the P rat may be involved in regulating ethanol
      self-administration. In addition, chronic operant ethanol self-administration
      and/or repeated treatments with a 5-HT(3) receptor antagonist may alter neuronal
      circuitry within the posterior VTA.

PMID- 20682193
TI  - Limited access to ethanol increases the number of spontaneously active dopamine
      neurons in the posterior ventral tegmental area of nondependent P rats.
AB  - Microdialysis experiments in alcohol-preferring (P) rats have shown that chronic
      ethanol exposure increases extracellular levels of dopamine (DA) in the nucleus
      accumbens. Because DA neuronal activity contributes to the regulation of DA
      overflow in terminal regions, we hypothesized that posterior ventral tegmental
      area (VTA) DA neuronal activity (firing frequency, burst activity, and/or the
      number of spontaneously active DA neurons) would be increased in P rats consuming
      ethanol compared with P rats consuming only water. In vivo electrophysiological
      techniques were used to evaluate the activity of single DA neurons in the
      posterior VTA. Our findings show that voluntary ethanol intake by nondependent P
      rats significantly increased the number of spontaneously active DA neurons in the
      posterior VTA compared with P rats that consumed only water. Firing frequency and
      burst activity did not differ between the two groups. These results suggest that
      adaptive changes occur in the mesolimbic DA system of nondependent P rats to
      increase the excitability of posterior VTA DA neurons and enhance DA release from
      nerve terminals in the nucleus accumbens.

PMID- 20682194
TI  - Alcohol self-administration in rats: Modulation by temporal parameters related to
      repeated mild social defeat stress.
AB  - Clinical evidence often points to stress as a cause or an antecedent to the
      development of drinking problems. Yet, animal models of alcohol drinking have
      yielded inconsistent evidence for a direct contribution of stress, and many
      studies have shown that stress suppresses alcohol consumption. The aim of the
      present study was to examine alcohol reward in animals exposed to repeated, mild
      social stress, and to determine whether alcohol drinking changes as a function of
      the temporal parameters of alcohol access relative to the stressor. Male Long
      Evans rats, trained to self-administer a 6% (wt/vol) alcohol solution using a
      sucrose-fading procedure, were exposed to five brief (5min) episodes of contact
      with an aggressive male. Full contact with the resident was limited to a single
      episode of defeat, whereas the following four encounters occurred with the
      subjects behind a protective wire mesh cage. Alcohol self-administration was
      measured 1 week prior to stress (baseline), on each day of stress exposure, and 1
      week following stress. Separate groups of animals were randomly assigned to self
      administer alcohol immediately prior, immediately following, or 2h following
      defeat stress. Stress preferentially increased alcohol drinking on stress
      exposure days, and further elevated the amount consumed 1 week following stress.
      Temporal parameters of alcohol access relative to the stressor were found to be
      important. Average alcohol consumption was greatest for animals drinking 2h
      postdefeat, whereas animals drinking immediately prior to or following the
      stressor did not show a significant increase in alcohol consumption. Results
      suggest that mild social defeat stress is sufficient to elicit increases in
      alcohol consumption in nonpreferring strains of rodents, provided alcohol access
      occurs at an optimal time interval after the social defeat experience.

PMID- 20682195
TI  - Sydenham's chorea: a practical overview of the current literature.
AB  - Sydenham's chorea is characterized by uncoordinated movements, emotional
      instability, and hypotonia. It can occur up to several months after group A beta
      hemolytic Streptococcus infection. A diagnosis of Sydenham's chorea in a patient
      with acute chorea involves an application of the Jones criteria and the exclusion
      of other causes of chorea. In patients with an atypical history or hemichorea,
      cranial magnetic resonance imaging is indicated to exclude other cerebral
      pathologies. A pathogenesis has not been elucidated, and therapy has not been
      investigated in placebo-controlled trials. Antibiotic treatment and a 2-week or 3
      week schedule of antibiotic prophylaxis are recommended. If the chorea is severe,
      valproate or carbamazepine can be effective. In more severely affected patients,
      dopamine receptor blocking agents or corticosteroids can be used.

PMID- 20682196
TI  - Clinical and brain imaging heterogeneity of severe microcephaly.
AB  - Microcephaly may be present at birth or develop postnatally. Classification
      according to the genetic cause cannot always predict the severity of the clinical
      course. The aim of this research was to group a large cohort of patients with
      primary microcephaly into more discrete subtypes, to optimize assessment of the
      patients based on their clinical and brain imaging findings. Medical records and
      brain images were reviewed for 4442 patients with brain malformations diagnosed
      and treated over 24 years and identified 247 patients classified as having
      microcephaly with simplified gyri alone or in association with additional brain
      abnormalities. For each case, clinical records were retrospectively reviewed for
      consanguinity, positive family history, sex, associated anomalies, and cranial
      magnetic resonance imaging. A subset (n = 12) of representative patients with the
      most complete available data was studied in greater detail, to define the most
      common subtypes and clinical presentations. Overall, four relatively common brain
      imaging presentations were identified, involving abnormalities in the gyral
      pattern, extra-axial space, and small size of the brainstem and cerebellum.
      Classifying patients with microcephaly according to brain imaging findings could
      enable more accurate counseling of the families with regard to prognosis.

PMID- 20682197
TI  - Complications of antipsychotic therapy in children with tourette syndrome.
AB  - Antipsychotics are effective at suppressing tics in Tourette syndrome, but can
      cause side effects. At a single center, all children with Tourette syndrome
      requiring antipsychotics were systematically monitored for metabolic and
      neurologic side effects every 6 months. Seventy-three children were followed for
      a mean of 39.6 months. Most children were treated primarily with an atypical
      antipsychotic. Thirty-three of 73 children (45%) developed lipid abnormalities.
      Compared with population-based mean lipid values for boys, total cholesterol, low
      density lipoprotein, high-density lipoprotein, and triglyceride levels were
      significantly higher in our male sample (P < 0.0001). Girls had significantly
      lower high-density lipoprotein concentrations (P = 0.0033). Thirty-six of 73
      (49%) children demonstrated abnormal body mass index percentiles. The odds of
      having lipid abnormalities were significantly higher in children with abnormal
      body mass indices (odds ratio, 6.0; 95% confidence interval, 2.15-16.7; P =
      0.0004). Three of 73 children developed neurologic complications. Metabolic
      complications of antipsychotics are common in children. These findings underscore
      the need to discuss benefits and risks before initiating therapy, and the
      importance of routinely monitoring growth and lipid profiles. Neurologic
      complications are uncommon, which is likely attributable to the primary use of
      atypical antipsychotics in this setting.

PMID- 20682198
TI  - Increased vulnerability to oxidative stress in pediatric migraine patients.
AB  - Little is known about the role of oxidative stress in the pathogenesis of
      pediatric migraine. The objective of the present study was to investigate, during
      a headache-free period, the activities of erythrocyte antioxidant enzymes in
      children and adolescents diagnosed with migraine. In all, 47 migraine patients
      (age range, 8-17 years; mean, 14.1 +/- 2.4 years, 14 with aura) and 35 control
      subjects were included. Superoxide dismutase, glutathione peroxidase, and
      catalase activities were measured in erythrocytes. Although superoxide dismutase
      activities did not differ between groups, both catalase and glutathione
      peroxidase activities were significantly lower in migraine patients (P = 0.001
      and P = 0.009, respectively). Activities of all three antioxidant enzymes were
      similar across migraine subgroups; there was no correlation with age and sex.
      These results confirm vulnerability to oxidative stress in pediatric migraine.
      Further studies and search for new therapeutic agents with antioxidant properties
      are needed.

PMID- 20682199
TI  - APOE gene epsilon polymorphism does not determine predisposition to ischemic
      stroke in children.
AB  - Ischemic stroke in children is relatively rare, but it remains an important
      medical problem. Previous studies on Polish children have implicated
      dyslipidemias as significant risk factors in stroke. To search for genetic
      factors associated with the disease, the possible association between
      apolipoprotein E gene epsilon polymorphism and childhood stroke was evaluated.
      The study population consisted of 243 individuals: 72 children with ischemic
      stroke and 100 of their biological parents and 71 children without any symptoms
      of stroke. The apolipoprotein E gene epsilon polymorphism was genotyped using
      restriction fragment length polymorphism methodology. To analyze the possible
      association between this polymorphism and stroke, the transmission disequilibrium
      test and the case-control model were used. No preferential distribution of any
      allele from parents to the affected children was observed. There were also no
      significant differences in genotype and allele distribution between patients and
      control subjects. Study findings did not confirm that epsilon polymorphism of the
      apolipoprotein E gene is a risk factor of ischemic stroke in children.

PMID- 20682200
TI  - Vagus nerve stimulation for refractory epilepsy in tuberous sclerosis.
AB  - The goal of the study was to assess the long-term seizure and neuropsychologic
      outcomes of patients with tuberous sclerosis and refractory epilepsy who received
      vagus nerve stimulator implantation. Eleven patients with a follow-up period of
      at least 12 months were studied retrospectively. The mean age at the time of
      implantation was 14 years (range, 2-35). Seizure outcome was rated as class I
      (>80% seizure frequency reduction) in 1 (9%), class II (50-79% reduction) in 7
      (63%), and class III (<50% reduction) in 3 (27%). No patient experienced
      permanent adverse effects after the procedure. A significant increase of adaptive
      behaviors and quality of life was observed. Patients who had implantation during
      childhood exhibited a greater improvement in cognitive and neuropsychologic
      functioning. Vagus nerve stimulation can be considered an effective and safe
      therapeutic option in patients with tuberous sclerosis and refractory epilepsy
      who are not candidates for epilepsy surgery.

PMID- 20682201
TI  - Ocular MECP2 protein expression in patients with and without Rett syndrome.
AB  - Rett syndrome is a neurodevelopmental disorder caused by mutations in the methyl
      CpG binding protein 2 gene (MECP2). The MECP2 protein is expressed primarily in
      neurons, and mutations in the gene lead to the clinical features of Rett syndrome
      in human patients and neurologic deficits in murine models. Visual function is
      relatively preserved in Rett syndrome patients, but the cause is unknown. The
      eyes of two Rett syndrome patients who died of the disease were analyzed; no
      gross or microscopic changes were found. MECP2 expression was examined using
      immunohistochemistry; nuclear protein expression was largely limited to ganglion
      cells and the portion of the inner nuclear layer populated by amacrine cells. No
      significant differences in MECP2 protein level or distribution were identified in
      the two eyes from the Rett syndrome patients, compared with 11 controls. The
      findings were compared with MECP2 expression in the brain of these two subjects
      and in MECP2-deficient mice. The findings suggest that the normally limited
      expression of MECP2 in visual pathway neurons may underlie the intact vision
      observed in Rett syndrome.

PMID- 20682202
TI  - Analysis of status epilepticus with Mycoplasma pneumoniae encephalitis.
AB  - Encephalitis is characterized clinically by fever, seizure, and an altered level
      of consciousness. Mycoplasma pneumoniae, a common respiratory pathogen, has been
      implicated as an etiology of encephalitis. The present study was designed to
      analyze status epilepticus associated with M. pneumoniae encephalitis in a series
      of children through retrospective review of cases between January 2002 and
      January 2008. Systematic clinical data were evaluated. Nine patients were
      identified: five girls and four boys, aged 4 years to 10 years. All were positive
      for M. pneumoniae by serology. Six of the nine children (67%) developed
      refractory status epilepticus. The major clinical symptoms included fever (100%)
      and upper respiratory symptoms (78%). The most common seizure type was primary
      focal with secondary generalized seizure (44%). The time of follow-up for this
      study ranged from 18 months to 86 months. At the end of the study period, two
      patients had died, seven had developed epilepsy or neurologic deficits, and none
      had returned to baseline. These data indicate that children with status
      epilepticus associated with M. pneumoniae encephalitis have high mortality and
      morbidity. Clinicians should be aware of the potential role of M. pneumoniae in
      status epilepticus.

PMID- 20682203
TI  - Bilateral striopallidodentate calcinosis with paroxysmal kinesigenic dyskinesia.
AB  - Bilateral striopallidodentate calcinosis is characterized by calcification of the
      basal ganglia and other gray matter structures. We describe a 16-year-old boy
      with paroxysmal kinesigenic dyskinesia. He exhibited mineralization in the basal
      ganglia, posterior thalami, and dentate nuclei bilaterally, and was diagnosed
      with sporadic bilateral striopallidodentate calcinosis. The paroxysmal
      kinesigenic dyskinesia responded to low-dose treatment with carbamazepine (200
      mg/day).

PMID- 20682204
TI  - Epilepsy: an anticipatory presentation of pediatric Wegener's granulomatosis.
AB  - Wegener's granulomatosis is a necrotizing, granulomatous vasculitis that
      primarily affects the respiratory tract and kidneys. It is rare in children. Few
      pediatric and adult case reports described seizures and central nervous system
      involvement at initial presentation, and none described central nervous system
      involvement in the absence of respiratory or renal disease. We describe a 17-year
      old girl with secondarily generalized seizures and granulomatous lesions in her
      brain. Although a systemic inflammatory disorder was suspected, she lacked
      evidence of pulmonary or renal involvement, so her signs were initially labeled
      as postinfectious encephalitis or variant acute disseminated encephalomyelitis.
      After 1 year of immunosuppressive therapy, she developed additional signs,
      leading to histologic confirmation on lung biopsy of Wegener's granulomatosis.
      This case emphasizes the need for close follow-up to monitor the asynchronous
      development of diagnostic clues when a systemic vasculitis is suspected but
      cannot be confirmed.

PMID- 20682205
TI  - High-dose ganciclovir in HHV-6 encephalitis of an immunocompetent child.
AB  - Encephalitis and other neurologic complications, including acute necrotizing
      encephalopathy, are associated with human herpesvirus-6 infection. Antiviral
      treatment against human herpesvirus-6 infection is indicated only for
      immunocompromised patients. We describe a 15-month-old immunocompetent child with
      severe human herpesvirus-6-induced encephalitis. The primary infection was
      characterized by human herpesvirus-6 DNA in cerebrospinal fluid and serum, the
      presence of serum human herpesvirus-6 immunoglobulin M antibodies, and a rise in
      serum human herpesvirus-6 immunoglobulin G antibodies. Magnetic resonance imaging
      demonstrated multiple, partly symmetric, necrotic lesions in the pons, medulla
      oblongata, thalamus, external capsules, and occipital subcortical and cortical
      areas. High-dose ganciclovir (18 mg/kg/day) was used as antiviral treatment,
      without side effects. A pharmacokinetic analysis of ganciclovir was performed.
      The initial recovery from severe disease was good. At 3-year follow-up,
      neurologic sequelae included epilepsy and ataxia. This case suggests that
      treatment with ganciclovir should be considered in human herpesvirus-6 central
      nervous system infections because the neurologic sequelae may otherwise be
      severe. Controlled, prospective, clinical trials are warranted, to analyze the
      pharmacokinetics of ganciclovir in infants.

PMID- 20682206
TI  - Brown-Sequard-plus syndrome because of penetrating trauma in children.
AB  - Brown-Sequard syndrome is an uncommon condition involving incomplete spinal cord
      injury, with ipsilateral motor and proprioception loss, contralateral pain, and
      decreased temperature. Brown-Sequard-plus syndrome is associated with additional
      neurologic findings involving the eyes, bowel, or bladder. We describe an
      adolescent with Brown-Sequard-plus syndrome attributable to a stab injury. Our
      patient's clinical features of spinal and neurogenic shock overlapped at
      presentation. He was managed with high-dose steroids, along with intense
      physiotherapy and rehabilitation, resulting in good neurologic recovery.
      Appropriate medical (and surgical, when indicated) management usually results in
      good to complete recovery of neurologic function, depending on the level and
      grade of injury. With the increasing incidence of gunshot wounds and stab
      injuries in children, pediatricians, including pediatric neurologists and
      emergency physicians, are more likely to encounter these types of spinal cord
      injuries in children.

PMID- 20682207
TI  - Paroxysmal kinesigenic dyskinesias and pseudohypo-parathyroidism type Ib.
AB  - Pseudohypoparathyroidism is a rare cause of paroxysmal dyskinesias. We describe
      an otherwise well 10-year-old girl who was diagnosed with
      pseudohypoparathyroidism type Ib after presenting with involuntary movements of
      the hands and feet that occurred while running or walking. Magnetic resonance
      imaging of the brain indicated T(1) hyperintensities of the bilateral basal
      ganglia. A computed tomography scan of the head revealed diffuse cerebral
      calcifications, most prominent in the basal ganglia. Treatment with calcitriol
      and calcium carbonate led to a complete resolution of her signs. We recommend
      that hypoparathyroidism always be considered in patients with kinesigenic
      paroxysmal dyskinesias, especially insofar as it is a treatable disorder.

PMID- 20682208
TI  - Anticonvulsant hypersensitivity syndrome treated with intravenous immunoglobulin.
AB  - Anticonvulsant hypersensitivity syndrome is a severe, potentially life
      threatening, reaction to the aromatic anticonvulsant medications. Reported here
      is a case of anticonvulsant hypersensitivity syndrome secondary to phenobarbital
      in a 2-year-old boy; he responded to drug withdrawal, corticosteroids, and
      intravenous immunoglobulin. The literature regarding treatment of this syndrome
      is reviewed.

PMID- 20682209
TI  - Presurgical prediction of motor functional loss using tractography.
AB  - The usefulness of magnetic resonance imaging tractography is demonstrated in the
      presurgical planning of an 8-year-old girl with intractable epilepsy. Imaging and
      intracranial electrode monitoring suggested a left hemispherectomy for complete
      control of her seizures. Although this child was hemiplegic, she retained
      considerable motor function in her right hand, and her parents and the epilepsy
      team voiced significant concern that she would lose right-hand function after a
      hemispherectomy. Tractography indicated near-complete absence of her left
      corticospinal tract and a more robust than normal corticospinal tract in the
      right hemisphere. This finding suggested that her right motor function had
      reorganized to the right hemisphere and the ipsilateral corticospinal tract.
      After surgery, her seizures were completely controlled, and no change in right
      motor activity was evident compared with her presurgical status. Tractography
      helped determine the extent of cortical resection and predict the extent of motor
      functional loss.

PMID- 20682210
TI  - Electroconvulsive therapy for catatonia in a boy with hydrocephalus and an
      arachnoid cyst.
AB  - We report on the successful use of electroconvulsive therapy in a 13-year-old boy
      with congenital hydrocephalus, a history of multiple shunt revisions, and a
      stable prepontine arachnoid cyst, who experienced profound catatonic
      deterioration. After initial shunt placement at age 20 months, the patient had
      followed normal motor, cognitive, and social developmental trajectories. Two
      uncomplicated shunt revisions were performed at ages 10 and 13 years. Three
      months after the last revision, the patient demonstrated multiple psychomotor
      signs, culminating in hospital admission for rigidity, posturing, waxy
      flexibility, stupor, mutism, and cessation of all oral intake. An extensive
      neurologic workup related to his preexisting conditions produced negative
      results, and a course of electroconvulsive therapy for acute catatonia was
      pursued, with outstanding improvement.

PMID- 20682211
TI  - Septo-optic dysplasia plus: a patient with diabetes insipidus.
AB  - The association of septo-optic dysplasia and cortical dysplasia is described as
      septo-optic dysplasia-plus. Reports on patients with septo-optic dysplasia-plus
      have been rare. We describe a 4-year-old girl with septo-optic dysplasia-plus
      syndrome, characterized by septo-optic dysplasia with schizencephaly, pachygyria,
      and diabetes insipidus.

PMID- 20682212
TI  - Adolescent substance use disorders. Foreword: the elephant in the room.

PMID- 20682213
TI  - Adolescent substance use disorders. Preface: Been there, done that, and now what?
      Adolescent addictive behaviors from etiology to postvention.

PMID- 20682214
TI  - Epidemiologic trends of adolescent use of alcohol, tobacco, and other drugs.
AB  - This article provides an overview of drug and alcohol use and risk factors among
      American adolescents. Current trends indicate that tobacco, alcohol, and
      marijuana are the most frequently used substances among this age group. Further,
      the greatest risk factors for using these substances are being male, being White,
      being an older adolescent, engaging in sexual risk behaviors, having a family
      history of substance abuse, associating with peers who abuse substances, and
      lacking a sense of school commitment and connectedness. These findings underscore
      the need to involve communities, families, schools, and peer groups to
      effectively prevent and treat this problem.

PMID- 20682215
TI  - Genetic and environmental risk factors for adolescent-onset substance use
      disorders.
AB  - Substance dependence disorders are chronic relapsing disorders with immense
      societal consequences. Twin and family studies have found that there are critical
      genetic and environmental components in the inheritance of substance use
      disorders, and modern advances in genetics are making it possible to identify
      specific variants that may predispose an individual to these disorders.
      Adolescence is a crucial period for initiation, experimentation, and the
      establishment of more regular patterns of use of alcohol and other drugs.
      Adolescent substance use is a known risk factor for the development of later
      alcohol and substance use problems, as well as related externalizing disorders
      such as antisocial personality disorder. Understanding the early risk factors and
      processes that make these youths vulnerable to substance use disorders is crucial
      to the development of effective strategies for prevention. This article reviews
      the genetic origins of adolescent substance use problems and the potential this
      field of research offers for prevention.

PMID- 20682216
TI  - Neurobiology of adolescent substance use disorders: implications for prevention
      and treatment.
AB  - Adolescence represents a unique period of development with neuronal maturation
      accompanied by increases in behavioral risk taking. Although risky behavior is a
      likely marker of normative adolescent development, there is an early emergence of
      substance use disorders in this population. Adolescence represents a distinct
      period of vulnerability to substance use initiation and transitions to substance
      abuse and dependence. Of recent interest is understanding the neurobiology of
      adolescent substance use disorders, with adult studies being limited in their
      applicability to this developmentally sensitive maturation period and providing
      restricted insight into potential treatment and intervention. First, the authors
      review the neurobiology of adolescent substance use disorders and, second, the
      authors consider the implications of these findings for prevention and treatment.

PMID- 20682217
TI  - Development and vulnerability factors in adolescent alcohol use.
AB  - This article provides an overview of the characteristics of adolescent alcohol
      use, normative and subgroup variations in drinking behavior, and the important
      factors associated with an increased risk for developing alcohol problems in
      later adolescence and young adulthood. Parental or family histories of
      alcoholism, temperament traits, conduct problems, cognitive functioning, alcohol
      expectancies, and peer and other social relations are identified as factors
      influencing an adolescent's susceptibility for initiating a variety of alcohol
      use behaviors. The deviance prone model, proposed by Sher in 1991, is presented
      as an important tool for testing possible relationships among the various risk
      factors and their sequencing that leads to early adolescent alcohol use and drug
      initiation. It is also possible to extend the model to allow for an examination
      of the complex interplay of risk factors that lead to the development of alcohol
      use problems in late adolescence and young adults.

PMID- 20682218
TI  - Evidence-based interventions for preventing substance use disorders in
      adolescents.
AB  - Substantial progress has been made in developing prevention programs for
      adolescent drug abuse. The most effective interventions target salient risk and
      protective factors at the individual, family, and community levels and are guided
      by relevant psychosocial theories regarding the etiology of substance use and
      abuse. This article reviews the epidemiology, etiologic risk and protective
      factors, and evidence-based approaches that have been found to be most effective
      in preventing adolescent substance use and abuse. Exemplary school- and family
      based prevention programs for universal (everyone in population), selected
      (members of at-risk groups), and indicated (at-risk individuals) target
      populations are reviewed, along with model community-based prevention approaches.
      Challenges remain in widely disseminating evidence-based prevention programs into
      schools, families, and communities.

PMID- 20682219
TI  - Evidence for optimism: behavior therapies and motivational interviewing in
      adolescent substance abuse treatment.
AB  - This article reviews behavior therapies, motivational interviewing interventions,
      and combined behavioral-psychosocial therapies across 34 peer-reviewed
      publications. Studies were included if they involved youth with alcohol and other
      drug (AOD) use, included measures of AOD outcomes, and used controlled research
      designs with a control or comparison condition. The level of empirical support of
      the interventions was evaluated using established guidelines. The article
      determined that behavior therapies were "probably efficacious," and motivational
      interviewing interventions easily met the criteria for "promising." Because of
      small sample sizes, combined behavioral-psychosocial therapies marginally met the
      criteria for "promising." The findings from this article underscore the value of
      individual and group behavior therapies and motivational interviewing in helping
      reduce mild to serious AOD use among adolescents.

PMID- 20682220
TI  - Contingency management approaches for adolescent substance use disorders.
AB  - The addition of contingency management (CM) to the menu of effective treatments
      for adolescent substance abuse has generated excitement in the research and
      treatment communities. CM interventions are based on extensive basic science and
      clinical research evidence demonstrating that drug use is sensitive to
      systematically applied consequences. This article provides (a) a review of basic
      CM principles, (b) implementation guidelines, (c) a review of the clinical CM
      research targeting adolescent substance abuse, and (d) a discussion of
      implementation successes and challenges. Although the research base for CM with
      adolescents is in its infancy, there are multiple reasons for high expectations.

PMID- 20682221
TI  - Multidimensional family therapy: addressing co-occurring substance abuse and
      other problems among adolescents with comprehensive family-based treatment.
AB  - Adolescent substance abuse rarely occurs without other psychiatric and
      developmental problems, but it is often treated and researched as if it can be
      isolated from comorbid conditions. Few comprehensive interventions are available
      that effectively address the range of co-occurring problems associated with
      adolescent substance abuse. This article reviews the clinical interventions and
      research evidence supporting the use of Multidimensional Family Therapy (MDFT)
      for adolescents with substance abuse and co-occurring problems. MDFT is uniquely
      suited to address adolescent substance abuse and related disorders given its
      comprehensive interventions that systematically target the multiple interacting
      risk factors underlying many developmental disruptions of adolescence.

PMID- 20682222
TI  - From assessment reactivity to aftercare for adolescent substance abuse: are we
      there yet?
AB  - This article addresses less developed areas of clinical research that are of
      great importance for better understanding the therapeutic process along the
      continuum of care in youth with alcohol and other substance use disorders
      (AOSUD). These include the rationale, design, mechanisms of behavior change
      (MBCs), implementation, monitoring, and outcome-based modification of treatment
      continuum for youth with AOSUD. The specific objectives are: (1) present current
      knowledge pertaining to the pretreatment phase including the effect of baseline
      assessment on treatment outcome; (2) address potential MBCs in treatment; (3)
      discuss the importance of aftercare, also known as continued care, to prevent
      postintervention relapse; (4) consider how reconceptualization of therapeutic
      paradigms might advance the field, in particular treatment algorithm or adaptive
      treatment strategies addressing poor response to treatment.

PMID- 20682223
TI  - Pharmacotherapies for adolescent substance use disorders.
AB  - There is a paucity of research on pharmacotherapies in adolescents with substance
      use disorders. This paucity is partly because of the fact that most people with
      substance dependence do not get diagnosed until early adulthood, that is, after
      18 years of age. This article reviews pharmacotherapies used for aversion,
      substitution, anti-craving, and detoxification of alcohol, nicotine, cocaine, and
      opioids dependence. Adult research is referenced when applicable and generalized
      to adolescents with caution. Continued evaluation and development of
      pharmacotherapy for youth in controlled studies are needed to examine medication
      effectiveness, safety, potential for abuse, compliance, and potential
      interactions with other medications or substances of abuse.

PMID- 20682224
TI  - Management of the adolescent with substance use disorders and comorbid
      psychopathology.
AB  - Substance use disorders are common in youth, and co-occurring psychiatric
      disorders are present in the majority of cases. This article reviews clinical
      considerations unique to the population, including intricacies of assessment and
      special treatment considerations. Several psychotherapeutic intervention models
      are discussed, including cognitive-behavioral therapy, dialectic behavior
      therapy, motivational enhancement therapy/motivational interviewing, family
      behavior therapy, multidimensional family therapy, and multisystemic therapy.
      Research on psychopharmacologic treatment is limited, and primarily focuses on
      mood disorders and attention deficit/hyperactivity disorder. To maximize outcome,
      recommendations based on practice parameters promote integration of treatment
      modalities versus serial or concurrent treatment of co-occurring substance use
      and psychiatric disorders.

PMID- 20682226
TI  - Problematic use of energy drinks by adolescents.
AB  - Energy drinks (EDs) are caffeine-based beverages that commonly contain large
      doses of sugar, carbohydrates, and a variety of legal stimulants and supplements,
      such as guarana, taurine, ginseng, and vitamin B complex. These drinks are
      marketed for young people as natural alternatives that increase fun and improve
      physical and cognitive performance such as concentration, attention, and
      alertness. There are commonly held false perceptions that the consumption of EDs
      can reverse alcohol-related impairment, including motor coordination and visual
      reaction time, which are crucial for driving safety. This article reviews the
      literature on EDs and examines problematic use and potential negative
      consequences in young people. Special emphasis is devoted to safety concerns
      following combination of EDs with alcohol, which gives the user a false sense of
      control.

PMID- 20682227
TI  - Endoscopy and liver disease. Preface.

PMID- 20682225
TI  - Non-substance-addictive behaviors in youth: pathological gambling and problematic
      Internet use.
AB  - Adolescence is characterized by participation in multiple novel and potentially
      risky behaviors. Amongst these behaviors are gambling and use of the Internet,
      and excessive engagement in these activities (as seen in pathological gambling
      and problematic Internet use) may be accompanied by serious impairments in
      school, mental health, and social functioning. This article reviews the potential
      impact of pathological gambling and problematic Internet use in youth, the
      relevance of subsyndromal levels of participation, and how prevention and
      treatment strategies may be considered and tested within a developmental
      framework.

PMID- 20682228
TI  - Endoscopic sedation of patients with chronic liver disease.
AB  - Endoscopic procedures are often necessary in patients with chronic liver disease.
      The preprocedure evaluation of such patients should include an assessment of
      hepatic synthetic function and identification of neuropsychiatric findings
      suggestive of hepatic encephalopathy. It may be possible, in some cases, to
      perform diagnostic esophagogastroduodenoscopy without administration of sedation;
      this is desirable to eliminate the risks of sedation, especially encephalopathy.
      Nonetheless, most patients undergoing upper and lower endoscopy require sedation.
      Currently, the use of propofol is preferred to benzodiazepines and opioids for
      endoscopic sedation of patients with advanced liver disease due to its short
      biologic half-life and low risk of provoking hepatic encephalopathy. In
      appropriately selected patients, gastroenterologist-directed propofol
      administration seems safe.

PMID- 20682229
TI  - Current staging and diagnosis of gastroesophageal varices.
AB  - Portal hypertension is defined as an increase in hepatic sinusoidal pressure to 6
      mm Hg or higher. Cirrhosis is the most common cause of portal hypertension in the
      western world and results from increased resistance to blood flow at the hepatic
      sinusoidal level.

PMID- 20682230
TI  - Capsule endoscopy in portal hypertension.
AB  - Since the introduction of small bowel capsule endoscopy, and more recently of
      esophageal capsule endoscopy, these diagnostic tools have become available for
      the evaluation of the consequences of portal hypertension in the esophagus,
      stomach, and small intestine. The main advantage of the esophageal and the small
      bowel capsule is the relatively less invasiveness that could potentially increase
      patients' adherence to endoscopic screening/surveillance programs. When
      esophageal capsule endoscopy was compared with traditional gastroscopy, it showed
      good sensitivity and specificity in recognizing the presence and the size of
      esophageal varices. However, the results are not consistent among studies, and
      more data are needed.

PMID- 20682231
TI  - Endoscopic ultrasonography for the evaluation of portal hypertension.
AB  - Since the 1980s, endoscopic ultrasonography (EUS) has been useful in the
      evaluation of portal hypertension, either for the diagnostic aspects or for the
      evaluation of therapy and risk of bleeding. More recently, it has been described
      as a method for guiding interventions such as variceal injection, portal vein
      catheterization, or even for creating an intrahepatic portosystemic shunt in the
      animal laboratory. The new generation of radial electronic echoendoscopes is
      equipped with color Doppler capability, allowing for measurement of any
      hemodynamic parameter of the portal circulation. This article summarizes the
      current knowledge on the role of EUS for the evaluation of portal hypertension.

PMID- 20682232
TI  - Role of endoscopy in primary prophylaxis for esophageal variceal bleeding.
AB  - Cirrhosis is the leading cause of portal hypertension in the Western world. From
      a clinical standpoint, the most significant consequence of portal hypertension is
      the development of esophageal varices. Despite the many advances in the
      management of variceal bleeding, it remains a life-threatening complication of
      portal hypertension. Primary prophylaxis to prevent the first bleeding episode in
      patients with cirrhosis and esophageal varices is therefore critically important
      in the management of patients with cirrhosis.

PMID- 20682233
TI  - Management of acute variceal bleeding: emphasis on endoscopic therapy.
AB  - Acute variceal bleeding is one of the most serious and feared complications of
      patients with portal hypertension. The most common cause of portal hypertension
      is advanced liver disease. Patients with esophageal and gastric varices may bleed
      because of a progressive increase in portal pressure that causes them to grow and
      finally rupture. This article will review the current management strategies for
      acute variceal bleeding with emphasis on endoscopic therapy for the acute
      episode.

PMID- 20682234
TI  - Endoscopic therapy for gastric varices.
AB  - Bleeding from gastric varices (GVs) is generally more severe than bleeding from
      esophageal varices (EVs), but is thought to occur less frequently. Although
      several recent developments in the agents and the techniques have improved the
      outcome of GV bleeds no consensus has been reached on the optimum treatment.
      Because the blood flow in the GVs is relatively large and the bleeding is rapid
      and often profuse endoscopic means of treating bleeding GVs are the treatments of
      choice. Endoscopic injection of cyanoacrylate glue is the treatment of choice for
      the control of active bleeding of gastric avarices and to prevent rebleeding.
      This article reviews the current endoscopic treatment modalities used in gastric
      variceal bleeding, and the primary and secondary prophylaxis of gastric variceal
      bleeding.

PMID- 20682236
TI  - Refractory acute variceal bleeding: what to do next?
AB  - Current recommendations for the treatment of acute variceal bleeding (AVB) are to
      combine hemodynamic stabilization, antibiotic prophylaxis, pharmacologic agents,
      and endoscopic treatment. However, despite the application of the current gold
      standard pharmacologic and endoscopic treatment, failure to control bleeding or
      early rebleed within 5 days still occurs in 15% to 20% of patients with AVB. In
      case of treatment failure of the acute bleeding episode, if bleeding is mild and
      the patient is hemodynamically stable, a second endoscopic therapy may be
      attempted. If this fails, or if bleeding is severe, it is usually controlled
      temporarily with balloon tamponade until a definitive derivative treatment is
      applied. Transjugular intrahepatic portosystemic shunt is highly effective in
      this situation; however, despite the control of bleeding, a high proportion of
      these patients die of liver and multiorgan failure. Strategies intended to
      improve the prognosis of these patients should focus on identifying those high
      risk patients in whom standard therapy is likely to fail, and who are therefore
      candidates for more aggressive therapies early after the development of AVB.

PMID- 20682235
TI  - Management of gastropathy and gastric vascular ectasia in portal hypertension.
AB  - Portal hypertensive gastropathy and gastric antral vascular ectasia may cause
      gastrointestinal hemorrhage in patients with portal hypertension. Whereas the
      former presents exclusively in patients with portal hypertension, gastric antral
      vascular ectasia can also be observed in patients with other conditions.
      Diagnosis is established with upper gastrointestinal endoscopy, although some
      cases may require a biopsy to confirm the diagnosis. The most frequent
      manifestation is ferropenic anemia, which may become transfusion dependent.
      Treatment in portal hypertensive gastropathy is focused on portal pressure
      reducing drugs, mainly nonselective beta-blockers, whereas in gastric antral
      vascular ectasia treatment is based on endoscopic ablation. More invasive options
      can be used if first-line therapies fail, although these should be evaluated on a
      case-by-case basis.

PMID- 20682237
TI  - The role of endoscopy in secondary prophylaxis of esophageal varices.
AB  - The rate of rebleeding from esophageal varices remains appreciably high after
      cessation of acute esophageal variceal hemorrhage. Many measures have been
      developed to prevent the occurrence of rebleeding. Endoscopic therapy plays a
      central role in the prevention of variceal bleeding. In the 1980s sclerotherapy
      played a pivotal role in the prevention of variceal rebleeding, but now yields to
      endoscopic variceal ligation. Compared with sclerotherapy, a lower incidence of
      complications and rebleeding is associated with banding ligation. On the other
      hand, beta-blockers are also noted to be able to reduce portal pressure, leading
      to the reduction of variceal rebleeding. The reduction of variceal rebleeding
      with beta-blockers plus nitrates is as effective as banding ligation. The
      combination of beta-blockers and endoscopic variceal ligation has proven to be
      more efficacious than banding ligation alone in the reduction of variceal
      rebleeding and is the treatment of choice for patients with failure in either
      medical or endoscopic therapy. Patients with repeated rebleeding despite
      endoscopic therapies may require transjugular intrahepatic portosystemic stent
      shunt or shunt operation as a rescue therapy.

PMID- 20682238
TI  - Endoscopic ultrasound and fine-needle aspiration for the diagnosis of
      hepatocellular carcinoma.
AB  - Hepatocellular cancer (HCC) is the sixth most common cancer in the world with an
      estimated incidence of more than 650,000 cases per year. The major risk factor
      associated with the development of HCC is cirrhosis caused by viral hepatitis B
      or C and chronic alcohol consumption. The overall prognosis of patients with HCC
      remains poor with 5-year survival estimates that range between 0% and 10%. This
      dismal prognosis is mainly the result of the advanced stage of HCC at
      presentation and the background cirrhosis. Systematic screening of high-risk
      patients is key to an early diagnosis of HCC allowing for the use of an
      appropriate treatment modality. This article briefly reviews the current
      guidelines for surveillance and diagnosis of HCC in high-risk patients and the
      potential role of endoscopic ultrasound and fine-needle aspiration for the
      diagnosis of small HCC.

PMID- 20682239
TI  - Endoscopic retrograde cholangiopancreatography in the diagnosis and management of
      cholangiocarcinoma.
AB  - Cholangiocarcinomas (CCAs) are rare malignancies that arise from the biliary
      epithelium. Intrahepatic CCAs usually present as mass lesions that are
      asymptomatic or cause nonspecific systemic symptoms such as fatigue, fever, and
      weight loss. Hilar and extrahepatic tumors most commonly present with jaundice,
      though cholangitis also can be seen. Tumor markers such as carbohydrate antigen
      19-9 and carcinoembryonic antigen have been used to diagnose CCA, but these are
      nonspecific and may be elevated in infection, inflammation, or any obstruction.
      Endoscopic retrograde cholangiopancreatography (ERCP) has been used for the
      diagnosis and management of CCA for many years. This article summarizes the data
      regarding the application of ERCP in the diagnosis and management of CCA.

PMID- 20682240
TI  - Endoscopic retrograde cholangiopancreatography in diagnosis and treatment of
      primary sclerosing cholangitis.
AB  - Primary sclerosing cholangitis is characterized by progressive fibrosing
      obliteration of the biliary tract. In some cases the disease is restricted to the
      small bile ducts, but most patients develop fibrotic stenoses of the larger bile
      ducts. Despite advances in magnetic resonance cholangiography, in unclear cases
      endoscopic retrograde cholangiography is necessary to make the correct diagnosis.
      In patients with total or subtotal strictures of the large bile ducts, these so
      called dominant stenoses may be treated by endoscopic balloon dilatation and/or
      stent placement, though in the large majority of cases a stent placement is not
      necessary. Several studies showed an improvement of biochemical parameters after
      endoscopic treatment, and actuarial survival in these patients was improved
      compared with predicted survival. Endoscopic retrograde cholangiography allows
      tissue sampling, brush cytology, and bile analysis for early detection of
      cholangiocarcinoma, a major complication of primary sclerosing cholangitis.
      Despite successful endoscopic opening of bile duct stenoses, patients often
      progress to liver failure, leading to liver transplantation as the treatment of
      choice.

PMID- 20682241
TI  - Endoscopic management of biliary complications after liver transplantation.
AB  - Complications of the biliary tract are an important cause of morbidity and
      mortality after liver transplantation. The most frequent complications are
      anastomotic biliary tract strictures, bile leaks, and bile duct stones. The
      estimated incidence of these complications ranges between 5% and 25%, although
      rates have been decreasing in recent years. Most complications can be managed
      successfully with endoscopic retrograde cholangiography. This article reviews the
      various biliary complications after liver transplantation (both deceased donor
      and living-related donor) and their endoscopic management.

PMID- 20682242
TI  - Redox atlas of the mouse. Immunohistochemical detection of glutaredoxin-,
      peroxiredoxin-, and thioredoxin-family proteins in various tissues of the
      laboratory mouse.
AB  - BACKGROUND: Oxidoreductases of the thioredoxin family of proteins have been
      thoroughly studied in numerous cellular and animal models mimicking human
      diseases. Despite of their well documented role in various disease conditions, no
      systematic information on the presence of these proteins is available. METHODS:
      Here, we have systematically analyzed the presence of some of the major
      constituents of the glutaredoxin (Grx)-, peroxiredoxin (Prx)-, and thioredoxin
      (Trx)-systems, i.e. Grx1, Grx2, Grx3 (TXNL-2/PICOT), Grx5, nucleoredoxin (Nrx),
      Prx1, Prx2, Prx3, Prx4, Prx5, Prx6, Trx1, thioredoxin reductase 1 (TrxR1), Trx2,
      TrxR2, and gamma-glutamyl cysteine synthetase (gamma-GCS) in various tissues of
      the mouse using immunohistochemistry. RESULTS: The identification of the Trx
      family proteins in the central nervous system, sensory organs, digestive system,
      lymphatic system, reproductive system, urinary system, respiratory system,
      endocrine system, skin, heart, and muscle revealed a number of significant
      differences between these proteins with respect to their distribution in these
      tissues. CONCLUSION: Our results imply more specific functions and interactions
      between the proteins of this family than previously assumed. GENERAL
      SIGNIFICANCE: Crucial functions of Trx family proteins have been demonstrated in
      various disease conditions. A detailed overview on their distribution in various
      tissues will be helpful to fully comprehend their potential role and the
      interactions of these proteins in the most thoroughly studied model for human
      diseases-the laboratory mouse. This article is part of a Special Issue entitled
      Human and Murine Redox Protein Atlases.

PMID- 20682243
TI  - Crystallizing transmembrane peptides in lipidic mesophases.
AB  - Structure determination of membrane proteins by crystallographic means has been
      facilitated by crystallization in lipidic mesophases. It has been suggested,
      however, that this so-called in meso method, as originally implemented, would not
      apply to small protein targets having </=4 transmembrane crossings. In our study,
      the hypothesis that the inherent flexibility of the mesophase would enable
      crystallogenesis of small proteins was tested using a transmembrane
      pentadecapeptide, linear gramicidin, which produced structure-grade crystals.
      This result suggests that the in meso method should be considered as a viable
      means for high-resolution structure determination of integral membrane peptides,
      many of which are predicted to be coded for in the human genome.

PMID- 20682244
TI  - Tackling force-field bias in protein folding simulations: folding of Villin HP35
      and Pin WW domains in explicit water.
AB  - The ability to fold proteins on a computer has highlighted the fact that existing
      force fields tend to be biased toward a particular type of secondary structure.
      Consequently, force fields for folding simulations are often chosen according to
      the native structure, implying that they are not truly "transferable." Here we
      show that, while the AMBER ff03 potential is known to favor helical structures, a
      simple correction to the backbone potential (ff03( *)) results in an unbiased
      energy function. We take as examples the 35-residue alpha-helical Villin HP35 and
      37 residue beta-sheet Pin WW domains, which had not previously been folded with
      the same force field. Starting from unfolded configurations, simulations of both
      proteins in Amber ff03( *) in explicit solvent fold to within 2.0 A RMSD of the
      experimental structures. This demonstrates that a simple backbone correction
      results in a more transferable force field, an important requirement if
      simulations are to be used to interpret folding mechanism.

PMID- 20682245
TI  - Hill coefficients of a polymodal Monod-Wyman-Changeux model for ion channel
      gating.
AB  - Allosteric transitions of ion channels can be driven by multiple sources of free
      energies. One class of model for describing such transitions is the multistimulus
      Monod-Wyman-Changeux model, in which each stimulus interacts with a specific
      sensor on the protein and activation of the sensor is allosterically coupled to
      conformational changes of the protein. In general, when a protein is stressed by
      multiple stimuli, one stimulus can influence the response to another, which can
      result in both a shift of the midpoint of the dose-response curve and a change of
      the slope of the curve. Here I show that, for a Monod-Wyman-Changeux model with
      independent sensors, the different dose-response curves of open probability for
      one stimulus have the same slope at the same agonist concentration. In the other
      words, the slope of the dose-response curve for one stimulus is an intrinsic
      property of the sensors for that stimulus; it is independent of other stimuli or
      their sensor properties. As the dose-response curve for many receptors can be fit
      to a Boltzmann or Hill equation, this property provides a practical, usable test
      for applicability of such models.

PMID- 20682246
TI  - Shaping a morphogen gradient for positional precision.
AB  - Morphogen gradients, which provide positional information to cells in a
      developing tissue, could in principle adopt any nonuniform profile. To our
      knowledge, how the profile of a morphogen gradient affects positional precision
      has not been well studied experimentally. Here, we compare the positional
      precision provided by the Drosophila morphogenetic protein Bicoid (Bcd) in wild
      type (wt) embryos with embryos lacking an interacting cofactor. The Bcd gradient
      in the latter case exhibits decreased positional precision around mid-embryo
      compared with its wt counterpart. The domain boundary of Hunchback (Hb), a target
      activated by Bcd, becomes more variable in mutant embryos. By considering embryo
      to-embryo, internal, and measurement fluctuations, we dissect mathematically the
      relevant sources of fluctuations that contribute to the error in positional
      information. Using this approach, we show that the defect in Hb boundary
      positioning in mutant embryos is directly reflective of an altered Bcd gradient
      profile with increasing flatness toward mid-embryo. Furthermore, we find that
      noise in the Bcd input signal is dominated by internal fluctuations but, due to
      time and spatial averaging, the spatial precision of the Hb boundary is primarily
      affected by embryo-to-embryo variations. Our results demonstrate that the
      positional information provided by the wt Bcd gradient profile is highly precise
      and necessary for patterning precision.

PMID- 20682247
TI  - Quantifying a pathway: kinetic analysis of actin dendritic nucleation.
AB  - Progress in uncovering the reaction networks that underlie important cell
      functions is laying the groundwork for quantitative identification of protein
      interaction pathways. Since direct measurement of rate constants is not always
      feasible, the parameters are often inferred from multiple pieces of data using
      kinetic analyses based on appropriate mathematical models. The success of this
      approach relies on the sufficiency of available experimental data for a unique
      parameterization of the network. The concept of a rate-limiting step is applied
      to the analysis of experimental data that are usually used to quantify a pathway
      of actin dendritic nucleation, the Arp2/3-mediated mechanism that enables rapid
      changes of cell shape in response to external cues. The method yields analytical
      descriptions of the dynamics of polymerized actin and provides insights into how
      the experimental curves should be analyzed. It is shown that dynamics measured by
      pyrene-labeled actin assays with varying Arp2/3 concentrations are equally well
      described by two different rate-limiting steps: 1), binding of a nucleating
      complex to the side of a preexisting filament; or 2), its subsequent activation.
      To distinguish between the alternatives, we propose experiments with varying
      concentrations of actin monomers, taking advantage of the fact that the number of
      branches in the two cases depends differently on the initial monomer
      concentration. The idea is tested by simulating the proposed experiments with the
      use of spatial stochastic modeling.

PMID- 20682248
TI  - Modelling spatially regulated beta-catenin dynamics and invasion in intestinal
      crypts.
AB  - Experimental data (e.g., genetic lineage and cell population studies) on
      intestinal crypts reveal that regulatory features of crypt behavior, such as
      control via morphogen gradients, are remarkably well conserved among numerous
      organisms (e.g., from mouse and rat to human) and throughout the different
      regions of the small and large intestines. In this article, we construct a
      partial differential equation model of a single colonic crypt that describes the
      spatial distribution of Wnt pathway proteins along the crypt axis. The novelty of
      our continuum model is that it is based upon assumptions that can be directly
      related to processes at the cellular and subcellular scales. We use the model to
      predict how the distributions of Wnt pathway proteins are affected by mutations.
      The model is then extended to investigate how mutant cell populations can invade
      neighboring crypts. The model simulations suggest that cell crowding caused by
      increased proliferation and decreased cell loss may be sufficient for a mutant
      cell population to colonize a neighboring healthy crypt.

PMID- 20682249
TI  - Providing positional information with active transport on dynamic microtubules.
AB  - Microtubules (MTs) are dynamic protein polymers that change their length by
      switching between growing and shrinking states in a process termed dynamic
      instability. It has been suggested that the dynamic properties of MTs are central
      to the organization of the eukaryotic intracellular space, and that they are
      involved in the control of cell morphology, but the actual mechanisms are not
      well understood. Here, we present a theoretical analysis in which we explore the
      possibility that a system of dynamic MTs and MT end-tracking molecular motors is
      providing specific positional information inside cells. We compute the MT length
      distribution for the case of MT-length-dependent switching between growing and
      shrinking states, and analyze the accumulation of molecular motors at the tips of
      growing MTs. Using these results, we show that a transport system consisting of
      dynamic MTs and associated motor proteins can deliver cargo proteins
      preferentially to specific positions within the cell. Comparing our results with
      experimental data in the model organism fission yeast, we propose that the
      suggested mechanisms could play important roles in setting length scales during
      cellular morphogenesis.

PMID- 20682250
TI  - Rbx1 flexible linker facilitates cullin-RING ligase function before neddylation
      and after deneddylation.
AB  - In ubiquitination, cullin-RING E3 ubiquitin ligases (CRLs) assist in ubiquitin
      transfer from ubiquitin-conjugating enzyme E2 to the substrate. Neddylation,
      which involves NEDD8 transfer from E2 to E3-cullin, stimulates ubiquitination by
      inducing conformational change in CRLs. However, deneddylation, which removes
      NEDD8 from cullin, does not suppress ubiquitination in vivo, raising the question
      of how neddylation/deneddylation exerts its effects. Using molecular-dynamics
      simulations, we demonstrate that before neddylation occurs, the linker
      flexibility of Rbx1, a CRL component, leads to conformational changes in CRLs
      that allow neddylation and initiation of ubiquitination. These large NEDD8
      induced conformational changes are retained after deneddylation, allowing both
      initiation of the ubiquitination process and ubiquitin chain elongation after
      deneddylation. Furthermore, mutation of lysine, the cullin residue to which NEDD8
      covalently attaches, dramatically reduces CRL conformational changes, suggesting
      that the acceptor lysine allosterically regulates CRLs. Thus, our results imply
      that neddylation stimulates ubiquitination by CRL conformational control via
      lysine modification.

PMID- 20682251
TI  - Distribution of electromechanical delay in the heart: insights from a three
      dimensional electromechanical model.
AB  - In the intact heart, the distribution of electromechanical delay (EMD), the time
      interval between local depolarization and myocyte shortening onset, depends on
      the loading conditions. The distribution of EMD throughout the heart remains,
      however, unknown because current experimental techniques are unable to evaluate
      three-dimensional cardiac electromechanical behavior. The goal of this study was
      to determine the three-dimensional EMD distributions in the intact ventricles for
      sinus rhythm (SR) and epicardial pacing (EP) by using a new, to our knowledge,
      electromechanical model of the rabbit ventricles that incorporates a biophysical
      representation of myofilament dynamics. Furthermore, we aimed to ascertain the
      mechanisms that underlie the specific three-dimensional EMD distributions. The
      results revealed that under both conditions, the three-dimensional EMD
      distribution is nonuniform. During SR, EMD is longer at the epicardium than at
      the endocardium, and is greater near the base than at the apex. After EP, the
      three-dimensional EMD distribution is markedly different; it also changes with
      the pacing rate. For both SR and EP, late-depolarized regions were characterized
      with significant myofiber prestretch caused by the contraction of the early
      depolarized regions. This prestretch delays myofiber-shortening onset, and
      results in a longer EMD, giving rise to heterogeneous three-dimensional EMD
      distributions.

PMID- 20682252
TI  - Sodium-calcium exchange is essential for effective triggering of calcium release
      in mouse heart.
AB  - In cardiac myocytes, excitation-contraction coupling depends upon sarcoplasmic
      reticular Ca2+ release triggered by Ca2+ influx through L-type Ca2+ channels.
      Although Na+-Ca2+ exchange (NCX) is essential for Ca2+ extrusion, its
      participation in the trigger process of excitation-contraction coupling is
      controversial. To investigate the role of NCX in triggering, we examined Ca2+
      sparks in ventricular cardiomyocytes isolated from wild-type (WT) and cardiac
      specific NCX knockout (KO) mice. Myocytes from young NCX KO mice are known to
      exhibit normal resting cytosolic Ca2+ and normal Ca2+ transients despite reduced
      L-type Ca2+ current. We loaded myocytes with fluo-3 to image Ca2+ sparks using
      confocal microscopy in line-scan mode. The frequency of spontaneous Ca2+ sparks
      was reduced in KO myocytes compared with WT. However, spark amplitude and width
      were increased in KO mice. Permeabilizing the myocytes with saponin eliminated
      differences between spontaneous sparks in WT and KO mice. These results suggest
      that sarcolemmal processes are responsible for the reduced spark frequency and
      increased spark width and amplitude in KO mice. When myocytes were loaded with 1
      mM fluo-3 and 3 mM EGTA via the patch pipette to buffer diadic cleft Ca2+, the
      number of sparks triggered by action potentials was reduced by 60% in KO cells
      compared to WT cells, despite similar SR Ca2+ content in both cell types. When
      EGTA was omitted from the pipette solution, the number of sparks triggered in KO
      and WT myocytes was similar. Although the number of sparks was restored in KO
      cells, Ca2+ release was asynchronous. These results suggest that high
      subsarcolemmal Ca2+ is required to ensure synchronous triggering with short spark
      latency in the absence of NCX. In WT mice, high subsarcolemmal Ca2+ is not
      required for synchronous triggering, because NCX is capable of priming the diadic
      cleft with sufficient Ca2+ for normal triggering, even when subsarcolemmal Ca(2+)
      is lowered by EGTA. Thus, reducing subsarcolemmal Ca2+ with EGTA in NCX KO mice
      reveals the dependence of Ca2+ release on NCX.

PMID- 20682253
TI  - Irregularly appearing early afterdepolarizations in cardiac myocytes: random
      fluctuations or dynamical chaos?
AB  - Irregularly occurring early afterdepolarizations (EADs) in cardiac myocytes are
      traditionally hypothesized to be caused by random ion channel fluctuations. In
      this study, we combined 1), patch-clamp experiments in which action potentials
      were recorded at different pacing cycle lengths from isolated rabbit ventricular
      myocytes under several experimental conditions inducing EADs, including oxidative
      stress with hydrogen peroxide, calcium overload with BayK8644, and ionic stress
      with hypokalemia; 2), computer simulations using a physiologically detailed
      rabbit ventricular action potential model, in which repolarization reserve was
      reduced to generate EADs and random ion channel or path cycle length fluctuations
      were implemented; and 3), iterated maps with or without noise. By comparing
      experimental, modeling, and bifurcation analyses, we present evidence that noise
      induced transitions between bistable states (i.e., between an action potential
      with and without an EAD) is not sufficient to account for the large variation in
      action potential duration fluctuations observed in experimental studies. We
      conclude that the irregular dynamics of EADs is intrinsically chaotic, with
      random fluctuations playing a nonessential, auxiliary role potentiating the
      complex dynamics.

PMID- 20682254
TI  - Interactions of mitochondrial presequence peptides with the mitochondrial outer
      membrane preprotein translocase TOM.
AB  - TOM protein-conducting channels serve as the main entry sites into mitochondria
      for virtually all mitochondrial proteins. When incorporated into lipid bilayers,
      they form large, relatively nonspecific ion channels that are blocked by peptides
      derived from mitochondrial precursor proteins. Using single-channel electrical
      recordings, we analyzed the interactions of mitochondrial presequence peptides
      with single TOM pores. The largest conductance state of the translocon represents
      the likely protein-conducting conformation of the channel. The frequency (but not
      the duration) of the polypeptide-induced blockage is strongly modulated by the
      substrate concentration. Structural differences between substrates are reflected
      in characteristic blockage frequencies and duration of blockage. To our
      knowledge, this study provides first quantitative data regarding the kinetics of
      polypeptide interaction with the mitochondrial TOM machinery.

PMID- 20682255
TI  - Polymer partitioning and ion selectivity suggest asymmetrical shape for the
      membrane pore formed by epsilon toxin.
AB  - Using poly-(ethylene glycol)s of different molecular weights, we probe the
      channels formed in planar lipid bilayers by epsilon toxin secreted by the
      anaerobic bacterium Clostridium perfringens. We find that the pore is highly
      asymmetric. The cutoff size of polymers entering the pore through its opening
      from the cis side, the side of toxin addition, is approximately 500 Da, whereas
      the cutoff size for the polymers entering from the trans side is approximately
      2300 Da. Comparing these characteristic molecular weights with those reported
      earlier for OmpF porin and the alpha-Hemolysin channel, we estimate the radii of
      cis and trans openings as 0.4 nm and 1.0 nm, respectively. The simplest geometry
      corresponding to these findings is that of a truncated cone. The asymmetry of the
      pore is also confirmed by measurements of the reversal potential at oppositely
      directed salt gradients. The moderate anionic selectivity of the channel is
      salted-out more efficiently when the salt concentration is higher at the trans
      side of the pore.

PMID- 20682256
TI  - Atomic force microscopy reveals the alternating subunit arrangement of the TRPP2
      TRPV4 heterotetramer.
AB  - There is evidence that polycystin-2 (TRPP2) interacts with two other members of
      the transient receptor potential (TRP) family, TRPC1 and TRPV4. We have
      previously shown that TRPP2 forms a heteromeric complex with TRPC1, with a 2:2
      stoichiometry and an alternating subunit arrangement. Here, we used
      coimmunoprecipitation to show that TRPP2 also interacts with TRPV4, but not with
      TRPA1 or TRPM8; hence, its promiscuity is limited. We then used atomic force
      microscopy to study the structure of the TRPV4 homomer and the interaction
      between TRPP2 and TRPV4. The molecular volume of V5-tagged TRPV4 isolated from
      singly-transfected tsA 201 cells indicated that it assembled as a homotetramer.
      The distribution of angles between pairs of anti-V5 antibodies bound to TRPV4
      particles had a large peak close to 90 degrees and a smaller peak close to 180
      degrees , again consistent with the assembly of TRPV4 as a homotetramer. In
      contrast, the angle distributions for decoration of the TRPP2-TRPV4 heteromer by
      either anti-Myc or anti-V5 antibodies had major peaks close to 180 degrees. This
      result indicates that TRPP2-TRPV4 assembles identically to TRPP2-TRPC1,
      suggesting a common subunit arrangement among heteromeric TRP channels.

PMID- 20682257
TI  - Linking the acetylcholine receptor-channel agonist-binding sites with the gate.
AB  - The gating isomerization of neuromuscular acetylcholine receptors links the
      rearrangements of atoms at two transmitter-binding sites with those at a distant
      gate region in the pore. To explore the mechanism of this reversible process, we
      estimated the gating rate and equilibrium constants for receptors with point
      mutations of alpha-subunit residues located between the binding sites and the
      membrane domain (N95, A96, Y127, and I49). The maximum energy change caused by a
      side-chain substitution at alphaA96 was huge (approximately 8.6 kcal/mol, the
      largest value measured so far for any alpha-subunit amino acid). A Phi-value
      analysis suggests that alphaA96 experiences its change in energy (structure)
      approximately synchronously with residues alphaY127 and alphaI49, but after the
      agonist molecule and other residues in loop A. Double mutant-cycle experiments
      show that the energy changes at alphaA96 are strongly coupled with those of
      alphaY127 and alphaI49. We identify a column of mutation-sensitive residues in
      the alpha-subunit that may be a pathway for energy transfer through the
      extracellular domain in the gating isomerization.

PMID- 20682258
TI  - Curling and local shape changes of red blood cell membranes driven by
      cytoskeletal reorganization.
AB  - Human red blood cells (RBCs) lack the actin-myosin-microtubule cytoskeleton that
      is responsible for shape changes in other cells. Nevertheless, they can display
      highly dynamic local deformations in response to external perturbations, such as
      those that occur during the process of apical alignment preceding merozoite
      invasion in malaria. Moreover, after lysis in divalent cation-free media, the
      isolated membranes of ruptured ghosts show spontaneous inside-out curling motions
      at the free edges of the lytic hole, leading to inside-out vesiculation. The
      molecular mechanisms that drive these rapid shape changes are unknown. Here, we
      propose a molecular model in which the spectrin filaments of the RBC cortical
      cytoskeleton control the sign and dynamics of membrane curvature depending on
      whether the ends of the filaments are free or anchored to the bilayer. Computer
      simulations of the model reveal that curling, as experimentally observed, can be
      obtained either by an overall excess of weakly-bound filaments throughout the
      cell, or by the flux of such filaments toward the curling edges. Divalent cations
      have been shown to arrest the curling process, and Ca2+ ions have also been
      implicated in local membrane deformations during merozoite invasion. These
      effects can be replicated in our model by attributing the divalent cation effects
      to increased filament-membrane binding. This process converts the curl-inducing
      loose filaments into fully bound filaments that arrest curling. The same basic
      mechanism can be shown to account for Ca2+-induced local and dynamic membrane
      deformations in intact RBCs. The implications of these results in terms of RBC
      membrane dynamics under physiological, pathological, and experimental conditions
      is discussed.

PMID- 20682259
TI  - Contribution of membrane elastic energy to rhodopsin function.
AB  - We considered the issue of whether shifts in the metarhodopsin I (MI)
      metarhodopsin II (MII) equilibrium from lipid composition are fully explicable by
      differences in bilayer curvature elastic stress. A series of six lipids with
      known spontaneous radii of monolayer curvature and bending elastic moduli were
      added at increasing concentrations to the matrix lipid 1-palmitoyl-2-oleoyl-sn
      glycero-3-phosphocholine (POPC) and the MI-MII equilibrium measured by flash
      photolysis followed by recording UV-vis spectra. The average area-per-lipid
      molecule and the membrane hydrophobic thickness were derived from measurements of
      the (2)H NMR order parameter profile of the palmitic acid chain in POPC. For the
      series of ethanolamines with different levels of headgroup methylation, shifts in
      the MI-MII equilibrium correlated with changes in membrane elastic properties as
      expressed by the product of spontaneous radius of monolayer curvature, bending
      elastic modulus, and lateral area per molecule. However, for the entire series of
      lipids, elastic energy explained the shifts only partially. Additional
      contributions correlated with the capability of the ethanolamine headgroups to
      engage in hydrogen bonding with the protein, independent of the state of
      ethanolamine methylation, with introduction of polyunsaturated sn-2 hydrocarbon
      chains, and with replacement of the palmitic acid sn-1 chains by oleic acid. The
      experiments point to the importance of interactions of rhodopsin with particular
      lipid species in the first layer of lipids surrounding the protein as well as to
      membrane elastic stress in the lipid-protein domain.

PMID- 20682260
TI  - Molecular dynamics simulations of mixed acidic/zwitterionic phospholipid
      bilayers.
AB  - Anionic lipids are key components in the cell membranes. Many cell-regulatory and
      signaling mechanisms depend upon a complicated interplay between them and
      membrane-bound proteins. Phospholipid bilayers are commonly used as model systems
      in experimental or theoretical studies to gain insight into the structure and
      dynamics of biological membranes. We report here 200-ns-long MD simulations of
      pure (DMPC and DMPG) and mixed equimolar (DMPC/DMPG, DMPC/DMPS, and DMPC/DMPA)
      bilayers that each contain 256 lipids. The intra- and intermolecular interaction
      patterns in pure and mixed bilayers are analyzed and compared. The effect of
      monovalent ions (Na+) on the formation of salt-bridges is investigated. In
      particular, the number of Na(+)-mediated clusters in the presence of DMPS is
      higher than with DMPG and DMPA. We observe a preferential clustering of DMPS (and
      to some extent DMPA) lipids together rather than with DMPC molecules, which can
      explain the phase separation observed experimentally for DMPC/DMPS and DMPC/DMPA
      bilayers.

PMID- 20682261
TI  - Material properties of lipid microdomains: force-volume imaging study of the
      effect of cholesterol on lipid microdomain rigidity.
AB  - The effect of cholesterol (CHOL) on the material properties of supported lipid
      bilayers composed of lipid mixtures that mimic the composition of lipid
      microdomains was studied by force-volume (FV) imaging under near-physiological
      conditions. These studies were carried out with lipid mixtures of
      dioleoylphosphatidylcholine, dioleoylphosphatidylserine, and sphingomyelin. FV
      imaging enabled simultaneous topology and force measurements of sphingomyelin
      rich domains (higher domain (HD)) and phospholipid-rich domains (lower domain
      (LD)), which allowed quantitative measurement of the force needed to puncture the
      lipid bilayer with or without CHOL. The force required to penetrate the various
      domains of the bilayer was probed using high- and low-ionic-strength buffers as a
      function of increasing amounts of CHOL in the bilayer. The progressive addition
      of CHOL also led to a decreasing height difference between HD and LD. FV imaging
      further demonstrated a lack of adhesion between the atomic force microscope tip
      and the HD or LD at loads below the breakthrough force. These results can lead to
      a better understanding of the role that CHOL plays in the mechanical properties
      of cellular membranes in modulating membrane rigidity, which has important
      implications for cellular mechanotransduction.

PMID- 20682262
TI  - Cell membrane tethers generate mechanical force in response to electrical
      stimulation.
AB  - Living cells maintain a huge transmembrane electric field across their membranes.
      This electric field exerts a force on the membrane because the membrane surfaces
      are highly charged. We have measured electromechanical force generation by cell
      membranes using optically trapped beads to detach the plasma membrane from the
      cytoskeleton and form long thin cylinders (tethers). Hyperpolarizing potentials
      increased and depolarizing potentials decreased the force required to pull a
      tether. The membrane tether force in response to sinusoidal voltage signals was a
      function of holding potential, tether diameter, and tether length. Membrane
      electromechanical force production can occur at speeds exceeding those of ATP
      based protein motors. By harnessing the energy in the transmembrane electric
      field, cell membranes may contribute to processes as diverse as outer hair cell
      electromotility, ion channel gating, and transport.

PMID- 20682263
TI  - Noninvasive measurements of integrin microclustering under altered membrane
      cholesterol levels.
AB  - Reported herein is a method that can be used to study the role of cholesterol in
      the microclustering of a ubiquitous class of membrane receptors, termed
      integrins. Integrin microclustering was measured using a fluorescence resonance
      energy transfer assay that does not require direct attachment of fluorescent
      donors or acceptors onto the integrins, and thus minimizes unwanted perturbations
      to integrin clustering. Membrane cholesterol levels were reduced using methyl
      beta-cyclodextrin (mbetaCD), as confirmed by Amplex Red assays of total cellular
      lipid or plasma membrane lipid extract. Subsequent changes in integrin
      microclustering were measured in cells expressing wild-type (WT) or mutant
      integrins. Although less integrin microclustering was measured after 27% membrane
      cholesterol depletion in a cell line expressing WT integrins, there was no
      statistically significant change for cells expressing alpha-cytoplasmic integrin
      mutants after a 45% reduction in plasma membrane cholesterol, and a significant
      increase in clustering for cells expressing ligand-binding domain integrin
      mutants after a 57% decrease in membrane cholesterol. These results are explained
      by differences in WT and mutant integrin partitioning into lipid nanodomains.
      Restoration of original cholesterol levels was used to confirm that the measured
      changes in membrane properties were cholesterol-dependent. No correlations
      between lipid diffusion and integrin microclustering were measured by means of
      fluorescence recovery after photobleaching using a fluorescent lipid mimetic.
      Similar lipid diffusion coefficients were measured after cholesterol depletion,
      irrespective of the integrins being expressed.

PMID- 20682265
TI  - Free energy calculations reveal rotating-ratchet mechanism for DNA supercoil
      relaxation by topoisomerase IB and its inhibition.
AB  - Topoisomerases maintain the proper topological state of DNA. Human topoisomerase
      I removes DNA supercoils by clamping a duplex DNA segment, nicking one strand at
      a phosphodiester bond, covalently attaching to the 3' end of the nick, and
      allowing the DNA downstream of the cut to rotate around the intact strand. Using
      molecular dynamics simulations and umbrella sampling free energy calculations, we
      show that the rotation of downstream DNA in the grip of the enzyme that brings
      about release of positive or negative supercoils occurs by thermally assisted
      diffusion on ratchet energy profiles. The ratchetlike free-energy-versus-rotation
      profile that we compute provides a model for the function of topoisomerase in
      which the periodic maxima along the profile modulate the rate of supercoil
      relaxation, while the minima provide metastable conformational states for DNA
      religation. The results confirm previous experimental and computational work, and
      suggest that relaxation of the two types of supercoils involves distinct protein
      pathways. Additionally, simulations performed with the ternary complex of
      topoisomerase, DNA, and the chemotherapeutic drug topotecan show important
      differences in the mechanisms for supercoil relaxation when the drug is present,
      accounting for the relative values of relaxation rates measured in single
      molecule experiments. Good agreement is found between rate constants from tweezer
      experiments and those calculated from simulations. Evidence is presented for the
      existence of semiopen states of the protein, which facilitate rotations after the
      initial one, as a result of biasing the protein into a conformation more
      favorable to strand rotation than the closed state required for nicking of the
      DNA.

PMID- 20682264
TI  - Electron microscopy and persistence length analysis of semi-rigid smooth muscle
      tropomyosin strands.
AB  - The structural mechanics of tropomyosin are essential determinants of its
      affinity and positioning on F-actin. Thus, tissue-specific differences among
      tropomyosin isoforms may influence both access of actin-binding proteins along
      the actin filaments and the cooperativity of actin-myosin interactions. Here, 40
      nm long smooth and striated muscle tropomyosin molecules were rotary-shadowed and
      compared by means of electron microscopy. Electron microscopy shows that striated
      muscle tropomyosin primarily consists of single molecules or paired molecules
      linked end-to-end. In contrast, smooth muscle tropomyosin is more a mixture of
      varying-length chains of end-to-end polymers. Both isoforms are characterized by
      gradually bending molecular contours that lack obvious signs of kinking. The
      flexural stiffness of the tropomyosins was quantified and evaluated. The
      persistence lengths along the shaft of rotary-shadowed smooth and striated muscle
      tropomyosin molecules are equivalent to each other (approximately 100 nm) and to
      values obtained from molecular-dynamics simulations of the tropomyosins; however,
      the persistence length surrounding the end-to-end linkage is almost twofold
      higher for smooth compared to cardiac muscle tropomyosin. The tendency of smooth
      muscle tropomyosin to form semi-rigid polymers with continuous and undampened
      rigidity may compensate for the lack of troponin-based structural support in
      smooth muscles and ensure positional fidelity on smooth muscle thin filaments.

PMID- 20682266
TI  - Revisiting the association of cationic groove-binding drugs to DNA using a
      Poisson-Boltzmann approach.
AB  - Proper modeling of nonspecific salt-mediated electrostatic interactions is
      essential to understanding the binding of charged ligands to nucleic acids.
      Because the linear Poisson-Boltzmann equation (PBE) and the more approximate
      generalized Born approach are applied routinely to nucleic acids and their
      interactions with charged ligands, the reliability of these methods is examined
      vis-a-vis an efficient nonlinear PBE method. For moderate salt concentrations,
      the negative derivative, SK(pred), of the electrostatic binding free energy,
      DeltaG(el), with respect to the logarithm of the 1:1 salt concentration, [M(+)],
      for 33 cationic minor groove drugs binding to AT-rich DNA sequences is shown to
      be consistently negative and virtually constant over the salt range considered
      (0.1-0.4 M NaCl). The magnitude of SK(pred) is approximately equal to the charge
      on the drug, as predicted by counterion condensation theory (CCT) and observed in
      thermodynamic binding studies. The linear PBE is shown to overestimate the
      magnitude of SK(pred), whereas the nonlinear PBE closely matches the experimental
      results. The PBE predictions of SK(pred) were not correlated with DeltaG(el) in
      the presence of a dielectric discontinuity, as would be expected from the CCT.
      Because this correlation does not hold, parameterizing the PBE predictions of
      DeltaG(el) against the reported experimental data is not possible. Moreover, the
      common practice of extracting the electrostatic and nonelectrostatic
      contributions to the binding of charged ligands to biopolyelectrolytes based on
      the simple relation between experimental SK values and the electrostatic binding
      free energy that is based on CCT is called into question by the results presented
      here. Although the rigid-docking nonlinear PB calculations provide reliable
      predictions of SK(pred), at least for the charged ligand-nucleic acid complexes
      studied here, accurate estimates of DeltaG(el) will require further development
      in theoretical and experimental approaches.

PMID- 20682267
TI  - Experimental evolution of adenylate kinase reveals contrasting strategies toward
      protein thermostability.
AB  - Success in evolution depends critically upon the ability of organisms to adapt, a
      property that is also true for the proteins that contribute to the fitness of an
      organism. Successful protein evolution is enhanced by mutational pathways that
      generate a wide range of physicochemical mechanisms to adaptation. In an earlier
      study, we used a weak-link method to favor changes to an essential but maladapted
      protein, adenylate kinase (AK), within a microbial population. Six AK mutants (a
      single mutant followed by five double mutants) had success within the population,
      revealing a diverse range of adaptive strategies that included changes in
      nonpolar packing, protein folding dynamics, and formation of new hydrogen bonds
      and electrostatic networks. The first mutation, AK(BSUB) Q199R, was essential in
      defining the structural context that facilitated subsequent mutations as revealed
      by a considerable mutational epistasis and, in one case, a very strong dependence
      upon the order of mutations. Namely, whereas the single mutation AK(BSUB) G213E
      decreases protein stability by >25 degrees C, the same mutation in the background
      of AK(BSUB) Q199R increases stability by 3.4 degrees C, demonstrating that the
      order of mutations can play a critical role in favoring particular molecular
      pathways to adaptation. In turn, protein folding kinetics shows that four of the
      five AK(BSUB) double mutants utilize a strategy in which an increase in the
      folding rate accompanied by a decrease in the unfolding rate results in
      additional stability. However, one mutant exhibited a dramatic increase in the
      folding relative to a modest increase in the unfolding rate, suggesting a
      different adaptive strategy for thermostability. In all cases, an increase in the
      folding rates for the double mutants appears to be the preferred mechanism in
      conferring additional stability and may be an important aspect of protein
      evolution. The range of overlapping as well as contrasting strategies for success
      illustrates both the power and subtlety of adaptation at even the smallest unit
      of change, a single amino acid.

PMID- 20682268
TI  - Casein kinase 2 beta-subunit is a regulator of bone morphogenetic protein 2
      signaling.
AB  - Bone morphogenetic proteins (BMPs) play a crucial role during embryonic
      development and regulate processes as diverse as neurogenesis, skeletal
      formation, and hematopoesis. They signal through a hetero-oligomer complex of BMP
      receptors. Binding of the ligand to the receptors activates several pathways,
      including Smad and p38. BMP signaling is controlled in the extracellular space,
      the plasma membrane, and the intracellular space; however, the mechanism of
      receptor signaling at the plasma membrane and proteins that regulate this process
      still need to be identified. The experiments presented here identify the protein
      kinase casein kinase II (CK2) as a BMP receptor type Ia (BRIa) interacting
      protein. Fluorescence resonance energy transfer revealed that this interaction
      occurs at the plasma membrane. BMP2 stimulation of C2C12 cells leads to the
      release of CK2 from BRIa. Blocking this interaction with specific peptides that
      inhibit the binding sites for CK2 on BRIa demonstrated a redistribution of BRIa
      on the plasma membrane. Signaling was initiated once CK2 was released from BRIa,
      leading to the mineralization of C2C12 cells. These data suggest that CK2 is a
      negative regulator of BMP signaling and osteoblast differentiation.

PMID- 20682269
TI  - Construction, MD simulation, and hydrodynamic validation of an all-atom model of
      a monoclonal IgG antibody.
AB  - At 150 kDa, antibodies of the IgG class are too large for their structure to be
      determined with current NMR methodologies. Because of hinge-region flexibility,
      it is difficult to obtain atomic-level structural information from the crystal,
      and questions regarding antibody structure and dynamics in solution remain
      unaddressed. Here we describe the construction of a model of a human IgG1
      monoclonal antibody (trastuzumab) from the crystal structures of fragments. We
      use a combination of molecular-dynamics (MD) simulation, continuum hydrodynamics
      modeling, and experimental diffusion measurements to explore antibody behavior in
      aqueous solution. Hydrodynamic modeling provides a link between the atomic-level
      details of MD simulation and the size- and shape-dependent data provided by
      hydrodynamic measurements. Eight independent 40 ns MD trajectories were obtained
      with the AMBER program suite. The ensemble average of the computed transport
      properties over all of the MD trajectories agrees remarkably well with the value
      of the translational diffusion coefficient obtained with dynamic light scattering
      at 20 degrees C and 27 degrees C, and the intrinsic viscosity measured at 20
      degrees C. Therefore, our MD results likely represent a realistic sampling of the
      conformational space that an antibody explores in aqueous solution.

PMID- 20682270
TI  - Attractive protein-polymer interactions markedly alter the effect of
      macromolecular crowding on protein association equilibria.
AB  - The dependence of the fluorescence of catalase upon the concentration of added
      superoxide dismutase (SOD) indicates that SOD binds to saturable sites on
      catalase. The affinity of SOD for these sites varies with temperature, and with
      the concentration of each of three nominally inert polymeric additives--dextran
      70, Ficoll 70, and polyethylene glycol 2000. At room temperature (25.0 degrees C)
      and higher, the addition of high concentrations of polymer is found to
      significantly enhance the affinity of SOD for catalase, but with decreasing
      temperature the enhancing effect of polymer addition diminishes, and at 8.0
      degrees C, addition of polymer has little or no effect on the affinity of SOD for
      catalase. The results presented here provide the first experimental evidence for
      the existence of competition between a repulsive excluded volume interaction
      between protein and polymer, which tends to enhance association of dilute
      protein, and an attractive interaction between protein and polymer, which tends
      to inhibit protein association. The net effect of high concentrations of polymer
      upon protein associations depends upon the relative strength of these two types
      of interactions at the temperature of measurement, and may vary significantly
      between different proteins and/or polymers.

PMID- 20682271
TI  - Uncovering specific electrostatic interactions in the denatured states of
      proteins.
AB  - The stability and folding of proteins are modulated by energetically significant
      interactions in the denatured state that is in equilibrium with the native state.
      These interactions remain largely invisible to current experimental techniques,
      however, due to the sparse population and conformational heterogeneity of the
      denatured-state ensemble under folding conditions. Molecular dynamics simulations
      using physics-based force fields can in principle offer atomistic details of the
      denatured state. However, practical applications are plagued with the lack of
      rigorous means to validate microscopic information and deficiencies in force
      fields and solvent models. This study presents a method based on coupled
      titration and molecular dynamics sampling of the denatured state starting from
      the extended sequence under native conditions. The resulting denatured-state
      pK(a)s allow for the prediction of experimental observables such as pH- and
      mutation-induced stability changes. I show the capability and use of the method
      by investigating the electrostatic interactions in the denatured states of wild
      type and K12M mutant of NTL9 protein. This study shows that the major errors in
      electrostatics can be identified by validating the titration properties of the
      fragment peptides derived from the sequence of the intact protein. Consistent
      with experimental evidence, our simulations show a significantly depressed pK(a)
      for Asp(8) in the denatured state of wild-type, which is due to a nonnative
      interaction between Asp(8) and Lys(12). Interestingly, the simulation also shows
      a nonnative interaction between Asp(8) and Glu(48) in the denatured state of the
      mutant. I believe the presented method is general and can be applied to extract
      and validate microscopic electrostatics of the entire folding energy landscape.

PMID- 20682272
TI  - Manipulation of conformational change in proteins by single-residue
      perturbations.
AB  - Using the perturbation-response scanning (PRS) technique, we study a set of 25
      proteins that display a variety of conformational motions upon ligand binding
      (e.g., shear, hinge, allosteric). In most cases, PRS determines single residues
      that may be manipulated to achieve the resulting conformational change. PRS
      reveals that for some proteins, binding-induced conformational change may be
      achieved through the perturbation of residues scattered throughout the protein,
      whereas in others, perturbation of specific residues confined to a highly
      specific region is necessary. Overlaps between the experimental and PRS
      calculated atomic displacement vectors are usually more descriptive of the
      conformational change than those obtained from a modal analysis of elastic
      network models. Furthermore, the largest overlaps obtained by the latter approach
      do not always appear in the most collective modes; there are cases where more
      than one mode yields comparable overlap sizes. We show that success of the modal
      analysis depends on an absence of redundant paths in the protein. PRS thus
      demonstrates that several relevant modes can be induced simultaneously by
      perturbing a single select residue on the protein. We also illustrate the
      biological relevance of applying PRS to the GroEL, adenylate kinase, myosin, and
      kinesin structures in detail by showing that the residues whose perturbation
      leads to precise conformational changes usually correspond to those
      experimentally determined to be functionally important.

PMID- 20682273
TI  - Acrylonitrile quenching of trp phosphorescence in proteins: a probe of the
      internal flexibility of the globular fold.
AB  - Quenching of Trp phosphorescence in proteins by diffusion of solutes of various
      molecular sizes unveils the frequency-amplitude of structural fluctuations. To
      cover the sizes gap between O(2) and acrylamide, we examined the potential of
      acrylonitrile to probe conformational flexibility of proteins. The distance
      dependence of the through-space acrylonitrile quenching rate was determined in a
      glass at 77 K, with the indole analog 2-(3-indoyl) ethyl phenyl ketone. Intensity
      and decay kinetics data were fitted to a rate, k(r) =k(0) exp[-(r -r(0))/r(e)],
      with an attenuation length r(e) = 0.03 nm and a contact rate k(0) = 3.6 x 10(10)
      s(-1). At ambient temperature, the bimolecular quenching rate constant (kq) was
      determined for a series of proteins, appositely selected to test the importance
      of factors such as the degree of Trp burial and structural rigidity. Relative to
      kq = 1.9 x 10(9) M(-1)s(-1) for free Trp in water, in proteins kq ranged from 6.5
      x 10(6) M(-1)s(-1) for superficial sites to 1.3 x 10(2) M(-1)s(-1) for deep
      cores. The short-range nature of the interaction and the direct correlation
      between kq and structural flexibility attest that in the microsecond-second
      timescale of phosphorescence acrylonitrile readily penetrates even compact
      protein cores and exhibits significant sensitivity to variations in dynamical
      structure of the globular fold.

PMID- 20682274
TI  - Quantitative imaging of human red blood cells infected with Plasmodium
      falciparum.
AB  - During its 48 h asexual reproduction cycle, the malaria parasite Plasmodium
      falciparum ingests and digests hemoglobin in excess of its metabolic requirements
      and causes major changes in the homeostasis of the host red blood cell (RBC). A
      numerical model suggested that this puzzling excess consumption of hemoglobin is
      necessary for the parasite to reduce the colloidosmotic pressure within the host
      RBC, thus preventing lysis before completion of its reproduction cycle. However,
      the validity of the colloidosmotic hypothesis appeared to be compromised by
      initial conflicts between model volume predictions and experimental observations.
      Here, we investigated volume and membrane area changes in infected RBCs (IRBCs)
      using fluorescence confocal microscopy on calcein-loaded RBCs. Substantial effort
      was devoted to developing and testing a new threshold-independent algorithm for
      the precise estimation of cell volumes and surface areas to overcome the
      shortfalls of traditional methods. We confirm that the volume of IRBCs remains
      almost constant during parasite maturation, suggesting that the reported increase
      in IRBCs' osmotic fragility results from a reduction in surface area and
      increased lytic propensity on volume expansion. These results support the general
      validity of the colloidosmotic hypothesis, settle the IRBC volume debate, and
      help to constrain the range of parameter values in the numerical model.

PMID- 20682275
TI  - Optimizing methods to recover absolute FRET efficiency from immobilized single
      molecules.
AB  - Microscopy-based fluorescence resonance energy transfer (FRET) experiments
      measure donor and acceptor intensities by isolating these signals with a series
      of optical elements. Because this filtering discards portions of the spectrum,
      the observed FRET efficiency is dependent on the set of filters in use.
      Similarly, observed FRET efficiency is also affected by differences in
      fluorophore quantum yield. Recovering the absolute FRET efficiency requires
      normalization for these effects to account for differences between the donor and
      acceptor fluorophores in their quantum yield and detection efficiency. Without
      this correction, FRET is consistent across multiple experiments only if the
      photophysical and instrument properties remain unchanged. Here we present what
      is, to our knowledge, the first systematic study of methods to recover the true
      FRET efficiency using DNA rulers with known fluorophore separations. We varied
      optical elements to purposefully alter observed FRET and examined protein samples
      to achieve quantum yields distinct from those in the DNA samples. Correction for
      calculated instrument transmission reduced FRET deviations, which can facilitate
      comparison of results from different instruments. Empirical normalization was
      more effective but required significant effort. Normalization based on single
      molecule photobleaching was the most effective depending on how it is applied.
      Surprisingly, per-molecule gamma-normalization reduced the peak width in the DNA
      FRET distribution because anomalous gamma-values correspond to FRET outliers.
      Thus, molecule-to-molecule variation in gamma has an unrecognized effect on the
      FRET distribution that must be considered to extract information on sample
      dynamics from the distribution width.

PMID- 20682276
TI  - Microimaging of oxygen concentration near live photosynthetic cells by electron
      spin resonance.
AB  - We present what is, to our knowledge, a new methodology for high-resolution three
      dimensional imaging of oxygen concentration near live cells. The cells are placed
      in the buffer solution of a stable paramagnetic probe, and electron spin
      resonance microimaging is employed to map out the probe's spin-spin relaxation
      time (T(2)). This information is directly linked to the concentration of the
      oxygen molecule. The method is demonstrated with a test sample and with a small
      amount of live photosynthetic cells (cyanobacteria), under conditions of darkness
      and light. Spatial resolution of approximately 30 x 30 x 100 microm is
      demonstrated, with approximately microM oxygen concentration sensitivity and sub
      fmol absolute oxygen sensitivity per voxel. The use of electron spin-resonance
      microimaging for oxygen mapping near cells complements the currently available
      techniques based on microelectrodes or fluorescence/phosphorescence. Furthermore,
      with the proper paramagnetic probe, it will also be readily applicable for
      intracellular oxygen microimaging, a capability which other methods find very
      difficult to achieve.

PMID- 20682277
TI  - Brightness analysis by Z-scan fluorescence fluctuation spectroscopy for the study
      of protein interactions within living cells.
AB  - Fluorescence fluctuation spectroscopy (FFS) quantifies interactions of
      fluorescently labeled proteins inside living cells by brightness analysis.
      Conventional FFS implicitly requires that the sample thickness exceeds the size
      of the observation volume. This condition is not always fulfilled when measuring
      cells. Cytoplasmic sections, especially, can be thinner than the axial size of
      the observation volume. The finite sample thickness introduces a brightness bias
      which, if not recognized, leads to an erroneous interpretation of the data. To
      avoid this artifact, we introduce z-scan FFS which consists of a fluorescence
      intensity z scan through the sample followed by an FFS measurement. To model the
      experimental z-scan data, a new PSF model had to be introduced. We use the
      intensity z scan together with the PSF model to determine the geometry of the
      sample and then extract the brightness from the FFS data. Cells expressing EGFP
      serve as a model system for testing the experimental approach. We demonstrate
      that z-scan FFS abolishes the brightness artifact and use the method to determine
      the oligomerization of cytoplasmic nuclear transport factor 2.

PMID- 20682278
TI  - Role of cytoskeleton in controlling the disorder strength of cellular nanoscale
      architecture.
AB  - Cytoskeleton is ubiquitous throughout the cell and is involved in important
      cellular processes such as cellular transport, signal transduction, gene
      transcription, cell-division, etc. Partial wave spectroscopic microscopy is a
      novel optical technique that measures the statistical properties of cell
      nanoscale organization in terms of the disorder strength. It has been found
      previously that the increase in the disorder strength of cell nanoarchitecture is
      one of the earliest events in carcinogenesis. In this study, we investigate the
      cellular components responsible for the differential disorder strength between
      two morphologically (and hence microscopically) similar but genetically altered
      human colon cancer cell lines, HT29 cells and Csk shRNA-transfected HT29 cells
      that exhibit different degrees of neoplastic aggressiveness. To understand the
      role of cytoskeleton in nanoarchitectural alterations, we performed selective
      drug treatment on the specific cytoskeletal components of these cell types and
      studied the effects of cytoskeletal organization on disorder strength
      differences. We report that altering the cell nanoarchitecture by disrupting
      cytoskeletal organization leads to the attenuation of the disorder strength
      differences between microscopically indistinguishable HT29 and CSK constructs. We
      therefore demonstrate that cytoskeleton plays a role in the control of cellular
      nanoscale disorder.

PMID- 20682279
TI  - Aggregation modulating elements in mutant human superoxide dismutase 1.
AB  - Mutations in superoxide dismutase 1 (SOD1) cause some forms of familial
      amyotrophic lateral sclerosis (fALS). Affected tissues of patients and transgenic
      mouse models of the disease accumulate misfolded and aggregated forms of the
      mutant protein. In the present study we have identified specific sequences in
      human SOD1 that modulate the aggregation of fALS mutant proteins. From our study
      of a panel of mutant proteins, we identify two sequence elements in human SOD1
      (residues 42-50 and 109-123) that are critical in modulating the aggregation of
      the protein. These sequences are components of the 4th and 7th beta-strands of
      the protein, and in the native structure are normally juxtaposed as elements of
      the core beta-barrel. Our data suggest that some type of intermolecular
      interaction between these elements may occur in promoting mutant SOD1
      aggregation.

PMID- 20682280
TI  - HIV and bone disease.
AB  - Advances in management have resulted in a dramatic decline in mortality for
      individuals infected with human immunodeficiency virus (HIV). This decrease in
      mortality, initially the result of improved prophylaxis and treatment of
      opportunistic infections but later mediated by the use of highly-active
      antiretroviral therapy (HAART) has led to the need to consider long-term
      complications of the disease itself, or its treatment. Bone disease is
      increasingly recognised as a concern. The prevalence of reduced BMD and possibly
      also fracture incidence are increased in HIV-positive individuals compared with
      HIV-negative controls. There are many potential explanations for this - an
      increased prevalence of established osteoporosis risk factors in the HIV-positive
      population, a likely direct effect of HIV infection itself and a possible
      contributory role of ARV therapy. At present, the assessment of bone disease and
      fracture risk remains patchy, with little or no guidance on identifying those at
      increased risk of reduced BMD or fragility fracture. Preventative and therapeutic
      strategies with bone specific treatments need to be developed. Limited data
      suggest bisphosphonates may be beneficial in conjunction with vitamin D and
      calcium supplementation in the treatment of reduced BMD in HIV-infected patients
      but larger studies of longer duration are needed. The safety and cost
      effectiveness of these and other treatments needs to be evaluated.

PMID- 20682282
TI  - Protein import into chloroplasts--how chaperones feature into the game.
AB  - Chloroplasts originated from an endosymbiotic event, in which an ancestral
      photosynthetic cyanobacterium was engulfed by a mitochondriate eukaryotic host
      cell. During evolution, the endosymbiont lost its autonomy by means of a massive
      transfer of genetic information from the prokaryotic genome to the host nucleus.
      Consequently, the development of protein import machineries became necessary for
      the relocation of proteins that are now nuclear-encoded and synthesized in the
      cytosol but destined for the chloroplast. Organelle biogenesis and maintenance
      requires a tight coordination of transcription, translation and protein import
      between the host cell and the organelle. This review focuses on the translocation
      complexes in the outer and inner envelope membrane with a special emphasis on the
      role of molecular chaperones. This article is part of a Special Issue entitled
      Protein translocation across or insertion into membranes.

PMID- 20682283
TI  - Early targeting events during membrane protein biogenesis in Escherichia coli.
AB  - All living cells have co-translational pathways for targeting membrane proteins.
      Co-translation pathways for secretory proteins also exist but mostly in
      eukaryotes. Unlike secretory proteins, the biosynthetic pathway of most membrane
      proteins is conserved through evolution and these proteins are usually
      synthesized by membrane-bound ribosomes. Translation on the membrane requires
      that both the ribosomes and the mRNAs be properly localized. Theoretically, this
      can be achieved by several means. (i) The current view is that the targeting of
      cytosolic mRNA-ribosome-nascent chain complexes (RNCs) to the membrane is
      initiated by information in the emerging hydrophobic nascent polypeptides. (ii)
      The alternative model suggests that ribosomes may be targeted to the membrane
      also constitutively, whereas the appropriate mRNAs may be carried on small
      ribosomal subunits or targeted by other cellular factors to the membrane-bound
      ribosomes. Importantly, the available experimental data do not rule out the
      possibility that cells may also utilize both pathways in parallel. In any case,
      it is well documented that a major player in the targeting pathway is the signal
      recognition particle (SRP) system composed of the SRP and its receptor (SR).
      Although the functional core of the SRP system is evolutionarily conserved, its
      composition and biological practice come with different flavors in various
      organisms. This review is dedicated mainly to the Escherichia (E.) coli SRP,
      where the biochemical and structural properties of components of the SRP system
      have been relatively characterized, yielding essential information about various
      aspects of the pathway. In addition, several cellular interactions of the SRP and
      its receptor have been described in E. coli, providing insights into their
      spatial function. Collectively, these in vitro studies have led to the current
      view of the targeting pathway [see (i) above]. Interestingly, however, in vivo
      studies of the role of the SRP and its receptor, with emphasis on the temporal
      progress of the pathway, elicited an alternative hypothesis [see (ii) above].
      This article is part of a Special Issue entitled Protein translocation across or
      insertion into membranes.

PMID- 20682281
TI  - Bone and glucose metabolism: a two-way street.
AB  - Evidence from rodent models indicates that undercarboxylated osteocalcin (ucOC),
      a product of osteoblasts, is a hormone affecting insulin production by the
      pancreas and insulin sensitivity in peripheral tissues, at least in part through
      enhanced secretion of adiponectin from adipocytes. Clinical research to test
      whether this relationship is found in humans is just beginning to emerge. Cross
      sectional studies confirm associations between total osteocalcin (OC), ucOC and
      glucose metabolism but cannot distinguish causality. To date, longitudinal
      studies have not provided a consistent picture of the effects of ucOC or OC on
      fasting glucose and insulin sensitivity. Further exploration into the
      physiological and mechanistic effects of ucOC and OC, in rodent models and
      clinical studies, is necessary to determine to what extent the skeleton regulates
      energy metabolism in humans.

PMID- 20682284
TI  - The role of hydrophobic interactions in ankyrin-spectrin complex formation.
AB  - Spectrin and ankyrin are the key components of the erythrocyte cytoskeleton. The
      recently published crystal structure of the spectrin-ankyrin complex has
      indicated that their binding involves complementary charge interactions as well
      as hydrophobic interactions. However, only the former is supported by biochemical
      evidence. We now show that nonpolar interactions are important for high affinity
      complex formation, excluding the possibility that the binding is exclusively
      mediated by association of distinctly charged surfaces. Along these lines we
      report that substitution of a single hydrophobic residue, F917S in ankyrin,
      disrupts the structure of the binding site and leads to complete loss of spectrin
      affinity. Finally, we present data showing that minimal ankyrin binding site in
      spectrin is formed by helix 14C together with the loop between helices 15 B/C.

PMID- 20682285
TI  - Crystal structures of two archaeal Pelotas reveal inter-domain structural
      plasticity.
AB  - Dom34 from Saccharomyces cerevisiae is one of the key players in no-go mRNA
      decay, a surveillance pathway by which an abnormal mRNA stalled during
      translation is degraded by an endonucleolytic cleavage. Its homologs called
      Pelota are found in other species. We showed previously that S. cerevisiae Dom34
      (domain 1) has an endoribonuclease activity, which suggests its direct catalytic
      role in no-go decay. Pelota from Thermoplasma acidophilum and Dom34 from S.
      cerevisiae have been structurally characterized, revealing a tripartite
      architecture with a significant difference in their overall conformations. To
      gain further insights into structural plasticity of the Pelota proteins, we have
      determined the crystal structures of two archaeal Pelotas from Archaeoglobus
      fulgidus and Sulfolobus solfataricus. Despite the structural similarity of their
      individual domains to those of T. acidophilum Pelota and S. cerevisiae Dom34,
      their overall conformations are distinct from those of T. acidophilum Pelota and
      S. cerevisiae Dom34. Different overall conformations are due to conformational
      flexibility of the two linker regions between domains 1 and 2 and between domains
      2 and 3. The observed inter-domain structural plasticity of Pelota proteins
      suggests that large conformational changes are essential for their functions.

PMID- 20682286
TI  - Outer membrane vesicles of Vibrio vulnificus deliver cytolysin-hemolysin VvhA
      into epithelial cells to induce cytotoxicity.
AB  - The Gram-negative bacterium Vibrio vulnificus produces cytotoxins that induce the
      acute death of host cells. However, the secretory mechanisms of such cytotoxins
      have not been extensively studied. Previously, we reported that substantial
      amounts of V. vulnificus cytolysin-hemolysin (VvhA) are produced in vivo during
      the bacterial infection in mice and that this cytotoxin, in conjunction with
      RtxA1, mediates cytotoxicity. In this study, we investigated whether V.
      vulnificus cells release outer membrane vesicles (OMVs), which are used by some
      Gram-negative bacteria to deliver virulence factors into host cells. We found
      that V. vulnificus produce OMVs and that these vesicles can induce host cell
      death. This process appears to be mediated by VvhA, as evidenced by the finding
      that OMVs isolated from VvhA-null mutants do not induce cytotoxicity. In
      addition, cholesterol sequestration in the host cells prevents OMV-mediated VvhA
      delivery, indicating that VvhA-bearing OMVs interact with cholesterol on the host
      cell surface. Furthermore, intracellular expression experiments revealed that
      VvhA-mediated cytotoxicity is driven by its N-terminal leukocidin domain.

PMID- 20682287
TI  - Antibiotic and synergistic effect of Leu-Lys rich peptide against antibiotic
      resistant microorganisms isolated from patients with cholelithiasis.
AB  - Pseudomonas aeruginosa has eventually developed resistance against flomoxef
      sodium, isepamicin and cefpiramide. Therefore, in this study, the antibacterial
      activity and synergistic effects of the amphipathic-derived P5-18mer
      antimicrobial peptide were tested against pathogens associated with
      cholelithiasis that have developed resistance against commonly used antibiotics.
      The results were then compared with the activities of the amphipathic-derived
      peptide, P5-18mer, melittin and common antibiotics. Growth inhibition of
      planktonic bacteria was tested using the National Committee for Clinical
      Laboratory Standards (NCCLS). The bactericidal activity of the antimicrobial
      peptides was measured using time-kill curves. Synergistic effects were evaluated
      by testing the effects of P5-18mer alone and in combination with flomoxef sodium,
      isepamicin or cefpiramide at 0.5xMIC. P5-18mer peptide displayed strong activity
      against pathogens and flomoxef sodium, isepamicin and cefpiramide-resistant
      bacteria cell lines obtained from a patient with gallstones; however, it did not
      exert cytotoxicity against the human keratinocyte HaCat cell line. In addition,
      the results of time-kill curves indicated that P5-18mer peptide exerted
      bactericidal activity against four strains of P. aeruginosa. Finally, the use of
      P5-18mer and antibiotics exerted synergistic effects against cell lines that were
      resistant to commonly used antibiotics. These results indicate that this class of
      peptides has a rapid microbicidal effect on flomoxef sodium, isepamicin and
      cefpiramide-resistant strains of P. aeruginosa. Therefore, these peptides may be
      used as a lead drug for the treatment of acquired pathogens from patients with
      cholelithiasis who are affected with antibiotic-resistant bacteria.

PMID- 20682288
TI  - Crystal structure of human programmed cell death 10 complexed with inositol
      (1,3,4,5)-tetrakisphosphate: a novel adaptor protein involved in human cerebral
      cavernous malformation.
AB  - Programmed cell death 10 (PDCD10) is a novel adaptor protein involved in human
      cerebral cavernous malformation, a common vascular lesion mostly occurring in the
      central nervous system. By interacting with different signal proteins, PDCD10
      could regulate various physiological processes in the cell. The crystal structure
      of human PDCD10 complexed with inositol-(1,3,4,5)-tetrakisphosphate has been
      determined at 2.3A resolution. The structure reveals an integrated dimer via a
      unique assembly that has never been observed before. Each PDCD10 monomer contains
      two independent domains: an N-terminal domain with a new fold involved in the
      tight dimer assembly and a C-terminal four-helix bundle domain that closely
      resembles the focal adhesion targeting domain of focal adhesion kinase. An eight
      residue flexible linker connects the two domains, potentially conferring mobility
      onto the C-terminal domain, resulting in the conformational variability of
      PDCD10. A variable basic cleft on the top of the dimer interface binds to
      phosphatidylinositide and regulates the intracellular localization of PDCD10. Two
      potential sites, respectively located on the two domains, are critical for
      recruiting different binding partners, such as germinal center kinase III
      proteins and the focal adhesion protein paxillin.

PMID- 20682289
TI  - Differential regulation of MRN (Mre11-Rad50-Nbs1) complex subunits and telomerase
      activity in cancer cells.
AB  - Several lines of evidence suggest that cancer progression is associated with up
      regulation or reactivation of telomerase and the underlying mechanism remains an
      active area of research. The heterotrimeric MRN complex, consisting of Mre11,
      Rad50 and Nbs1, which is required for the repair of double-strand breaks, plays a
      key role in telomere length maintenance. In this study, we show significant
      differences in the levels of expression of MRN complex subunits among various
      cancer cells and somatic cells. Notably, siRNA-mediated depletion of any of the
      subunits of MRN complex led to complete ablation of other subunits of the
      complex. Treatment of leukemia and prostate cancer cells with etoposide lead to
      increased expression of MRN complex subunits, with concomitant decrease in the
      levels of telomerase activity, compared to breast cancer cells. These studies
      raise the possibility of developing anti-cancer drugs targeting MRN complex
      subunits to sensitize a subset of cancer cells to radio- and/or chemotherapy.

PMID- 20682290
TI  - Differential gene expression profiling in blood from patients with digestive
      system cancers.
AB  - To develop a non-invasive and sensitive diagnostic test for cancer using
      peripheral blood, we evaluated gene expression profiling of blood obtained from
      patients with cancer of the digestive system and normal subjects. The expression
      profiles of blood-derived total RNA obtained from 39 cancer patients (11 colon
      cancer, 14 gastric cancer, and 14 pancreatic cancer) was clearly different from
      those obtained from 15 normal subjects. By comparing the gene expression profiles
      of cancer patients and normal subjects, 25 cancer-differentiating genes (p<5.0 x
      10(-6) and fold differences >3) were identified and an "expression index" deduced
      from the expression values of these genes differentiated the validation cohort
      (11 colon cancer, 8 gastric cancer, 18 pancreatic cancer, and 15 normal subjects)
      into cancer patients and normal subjects with 100% (37/37) and 87% (13/15)
      accuracy, respectively. Although, the expression profiles were not clearly
      different between the cancer patients, some characteristic genes were identified
      according to the stage and species of the cancer. Interestingly, many immune
      related genes such as antigen presenting, cell cycle accelerating, and apoptosis-
      and stress-inducing genes were up-regulated in cancer patients, reflecting the
      active turnover of immune regulatory cells in cancer patients. These results
      showed the potential relevance of peripheral blood gene expression profiling for
      the development of new diagnostic examination tools for cancer patients.

PMID- 20682291
TI  - Reduction of amyloid beta-peptide accumulation in Tg2576 transgenic mice by oral
      vaccination.
AB  - Alzheimer's disease (AD) is pathologically characterized by the presence of
      extracellular senile plaques and intracellular neurofibrillary tangles. Amyloid
      beta-peptide (Abeta) is the main component of senile plaques, and the
      pathological load of Abeta in the brain has been shown to be a marker of the
      severity of AD. Abeta is produced from the amyloid precursor protein by membrane
      proteases and is known to aggregate. Recently, immune-mediated cerebral clearance
      of Abeta has been studied extensively as potential therapeutic strategy. In
      previous studies that used a purified Abeta challenge in a mouse model of AD,
      symptomatic improvement was reported. However, a clinical Alzheimer's vaccine
      trial in the United States was stopped because of severe side effects.
      Immunization with the strong adjuvant used in these trials might have activated
      an inflammatory Th1 response. In this study, to establish a novel, safer, lower
      cost therapy for AD, we tested an oral vaccination in a wild-type and a
      transgenic mouse model of AD administered via green pepper leaves expressing GFP
      Abeta. Anti-Abeta antibodies were effectively induced after oral immunization. We
      examined the immunological effects in detail and identified no inflammatory
      reactions. Furthermore, we demonstrated a reduction of Abeta in the immunized AD
      model mice. These results suggest this edible vehicle for Abeta vaccination has a
      potential clinical application in the treatment of AD.

PMID- 20682292
TI  - New molecular mechanisms of the unexpectedly complex role of VEGF in ulcerative
      colitis.
AB  - The effects of VEGF on endothelial cells are mediated by different intracellular
      signaling cascades (e.g., Erk1/2, Akt, Src). VEGF plays a recently recognized
      role in ulcerative colitis (UC) pathogenesis, mostly by increasing vascular
      permeability and promoting the infiltration of inflammatory cells. We
      hypothesized that the excessive activation of signal transduction pathways, which
      is responsible for VEGF/VEGFR-2-mediated endothelial permeability (Src, Akt), is
      a new element in the pathogenesis of chronic UC. We demonstrated increased
      expression of pro-angiogenic growth factor VEGF and its receptor VEGFR-2 in
      colonic tissue during acute 6% iodoacetamide-induced UC in rats and chronic
      spontaneously developed UC in IL-10 knockout mice (IL-10 KO). Development of
      acute 6% iodoacetamide-induced UC in rats was accompanied by activation of Erk1/2
      and Src kinase, while expression of total proteins Erk1/2 and Src was unchanged.
      During chronic colitis phosphorylation (i.e., activation) of Erk1/2 was
      significantly decreased in IL-10 KO mice vs. wild-type mice. Levels of total
      Erk1/2 proteins were unchanged, but the expression of total Src protein as well
      as its phosphorylated form was significantly increased in IL-10 KO vs. wild-type
      mice. There were no changes in total Akt proteins, while levels of activated Akt
      (pAkt) were slightly increased in IL-10 KO vs. wild-type mice. We conclude that
      VEGF/VEGFR-2-associated signal transduction pathways, that mediate increased
      vascular permeability (Src, Akt), might play a central role in perpetuation of
      chronic experimental UC.

PMID- 20682293
TI  - Survival of retinal ganglion cells in slice culture provides a rapid screen for
      olfactory ensheathing cell preparations.
AB  - Transplants of olfactory ensheathing cells (OECs) cultured from the olfactory
      bulb are able to induce structural regeneration of severed central axons and
      return of function in rat models. For clinical purposes it would be preferable to
      obtain the cells from the more accessible olfactory mucosa in the nasal lining.
      However, in our laboratory preparations cultures from mucosal samples yielded
      around 5% of OECs compared with the 50% obtained from samples cultured from the
      bulb, and when transplanted these mucosal cell preparations were less effective
      at repair. There are a number of manipulations which may increase the OEC content
      and the effectiveness of mucosal preparations, but in vivo transplantation would
      be a highly labour intensive method for evaluating them. As a candidate for a
      high throughput assay to screen for beneficial effects of modifications to
      mucosal cells we here report the effects of co-culture of the cells with retinal
      explants. Both bulbar and mucosal cell preparations prolong the survival of the
      explants. Counts of the surviving retinal ganglion cells, identified by beta-III
      tubulin immunohistochemistry and by their axon trajectory, show that the bulbar
      cell preparations have around twice the potency of those from the mucosa. This in
      vitro system, therefore, provides a bioassay that discriminates bulbar and
      mucosal cell preparations, and a useful tool for evaluating the functional
      effects of manipulations of cultured mucosal preparations.

PMID- 20682294
TI  - Dual projections of tuberomammillary neurons to whisker-related, sensory and
      motor regions of the rat.
AB  - The primary goal of this study was to examine in the rat whether neurons in the
      tuberomammillary nucleus (TMN) provide axon collaterals to whisker-related,
      sensorimotor regions at cortical and brainstem levels, using two different
      retrograde tracers. When injections were made at primary sensory (S1) barrel
      field/primary whisker motor (M1) cortices, dual-projecting TMN neurons were
      observed mainly in the ventrolateral subdivision; the projection was almost
      exclusively ipsilateral. On the other hand, following injections of tracers into
      whisker-related, principal sensory trigeminal (Pr5)/lateral facial motor (Mo7)
      nuclei, dual-projecting cells were observed mainly in the dorsomedial
      subdivision; the projection was bilateral with a slight contralateral dominance.
      Taken together, the present observation demonstrated that each subdivision of the
      TMN possessed a differential functional organization with respect to its
      collateral projection to whisker-related sensorimotor targets, suggesting that
      the histaminergic projection might play a modulatory role in vibrissal
      sensorimotor integration, which allows the guidance of behavioral action
      essential for the survival of the animal.

PMID- 20682295
TI  - Suppressed phosphorylation of collapsin response mediator protein-2 in the
      hippocampus of HCNP precursor transgenic mice.
AB  - We previously reported a novel peptide, Hippocampal Cholinergic Neurostimulating
      Peptide (HCNP), which induces acetylcholine synthesis by increasing the amount of
      choline acetyltransferase (ChAT) in medial septal nuclei. The HCNP precursor
      protein (HCNP-pp), composed of 186 amino acids, is an inhibitory factor of the c
      Raf/MEK cascade and may be involved in fetal rat brain development via the
      inhibition of phosphorylation of Erk. To clarify the involvement of HCNP in
      hippocampal cholinergic circuitry, we previously generated HCNP-pp transgenic
      (HCNP-pp Tg) mice using the promoter of the alpha subunit of Ca(2+) calmodulin
      dependent protein kinase II (CaMKIIalpha). These mice showed increased levels of
      ChAT in medial septal nuclei at 12 weeks of age, and the phenotype of depressive
      mood at 30 weeks of age. Here, through proteomic analysis we investigated the
      alteration of protein expression in the hippocampus of HCNP-pp Tg mice compared
      with wild-type littermate mice. We demonstrate that the activation of collapsin
      response mediator protein-2 (CRMP-2) is increased in the transgenic mice at 12
      weeks of age when compared with wild-type littermate mice.

PMID- 20682296
TI  - Selection for intrinsic endurance modifies endocrine stress responsiveness.
AB  - Physical exercise dampens an individual's stress response and decreases symptoms
      of anxiety and depression disorders. While the extrinsic relationship of exercise
      and psychological state is established, their intrinsic relationship is
      unresolved. We investigated the potential intrinsic relationship of exercise with
      stress responsiveness using NIH rats bidirectionally selected for intrinsic
      endurance capacity. Selection resulted in two populations, one with high
      intrinsic endurance (high capacity runners; HCR) and one with low intrinsic
      endurance (low capacity runners; LCR). Animals from these populations were
      subjected to the elevated plus maze (EPM) and novel environment to assess levels
      of anxiety-like behavior, and to restraint stress to determine stress
      responsiveness. Pre-test plasma corticosterone levels and the response of plasma
      corticosterone to exposure to the EPM and restraint were analyzed using ELISA. A
      dexamethasone suppression test was performed to assess negative feedback tone of
      corticosterone release. Pre-test plasma corticosterone levels were similar
      between LCR and HCR, and these populations had similar behavioral and
      corticosterone responses to the EPM. Following restraint, HCR animals exhibited
      more anxiotypic behavior than LCR animals on the EPM, and exhibited an increase
      in plasma corticosterone following EPM and restraint that was not observed in LCR
      animals. HCR animals also exhibited more anxiotypic behavior in the novel
      environment compared to LCR animals. Plasma corticosterone levels were equally
      reduced in both populations following dexamethasone administration. Overall, our
      data suggest a positive genetic relationship between exercise endurance and
      stress responsiveness, which is at odds with the established extrinsic
      relationship of these traits.

PMID- 20682297
TI  - Ginsenosides Rb1 and Rg1 promote proliferation and expression of neurotrophic
      factors in primary Schwann cell cultures.
AB  - Ginsenoside Rb1 (GRb1) and ginsenoside Rg1 (GRg1), two major ingredients in
      ginseng root, have gained extensive attention because of its neuroprotective
      properties. Thus far, most of the studies on GRb1 and GRg1 have been focused on
      their neuroprotective effects on neurons. The potential beneficial effects of
      GRb1 and GRg1 on Schwann cells have not been investigated comprehensively. The
      present study was designed to examine the possible beneficial effect of GRb1 and
      GRg1 on proliferation and expression of nerve growth factor (NGF) and brain
      derived neurotrophic factor (BDNF) in Schwann cells. Schwann cells were incubated
      without or with GRb1 and GRg1 at different doses. The proliferation of Schwann
      cells was examined by cell counting. The expression and secretion of NGF and BDNF
      were examined by western blotting and ELISA. We found that both GRb1 and GRg1
      were capable of increasing the proliferation of, and the expression and secretion
      of NGF and BDNF in Schwann cells. Further studies showed that both GRb1 and GRg1
      were able to increase intracellular cyclic AMP (cAMP) level and protein kinase A
      (PKA) activity. Preincubation with 10 MUM H89 (a PKA inhibitor) significantly
      inhibited the beneficial effects of GRb1 and GRg1 on Schwann cells. These
      findings indicate that the beneficial effects of GRb1 and GRg1 on proliferation
      and expression of NGF and BDNF occurs mainly through the PKA pathway in cultured
      Schwann cells.

PMID- 20682299
TI  - Visual memory improved by non-invasive brain stimulation.
AB  - Our visual memories are susceptible to errors, but less so in people who have a
      more literal cognitive style. This inspired us to attempt to improve visual
      memory with non-invasive brain stimulation. We applied 13 min of bilateral
      transcranial direct current stimulation (tDCS) to the anterior temporal lobes.
      Our stimulation protocol included 3 conditions, each with 12 neurotypical
      participants: (i) left cathodal stimulation together with right anodal
      stimulation, (ii) left anodal stimulation together with right cathodal
      stimulation, and (iii) sham (control) stimulation. Only participants who received
      left cathodal stimulation (decrease in excitability) together with right anodal
      stimulation (increase in excitability) showed an improvement in visual memory.
      This 110% improvement in visual memory was similar to the advantage people with
      autism, who are known to be more literal, show over normal people in the
      identical visual task. Importantly, participants receiving stimulation of the
      opposite polarity (left anodal together with right cathodal stimulation) failed
      to show any change in memory performance. This is the first demonstration that
      visual memory can be enhanced in healthy people using non-invasive brain
      stimulation.

PMID- 20682298
TI  - Developmental characteristics of dendritic spines in the dentate gyrus of Fmr1
      knockout mice.
AB  - Fragile X Syndrome (FXS) is the most common form of inherited mental retardation.
      The neuroanatomical phenotype of adult FXS patients, as well as adult Fmr1
      knockout (KO) mice, includes elevated dendritic spine density and a spine
      morphology profile in neocortex that resembles younger individuals. Developmental
      studies in mouse neocortex have revealed a dynamic phenotype that varies with
      age, especially during the period of synaptic pruning. Here we investigated the
      hippocampal dentate gyrus to determine if the FXS spine phenotype is similarly
      tied to periods of maturation and pruning in this brain region. We used high
      voltage electron microscopy to characterize Golgi-stained spines along granule
      cell dendrites in Fmr1 KO and wildtype (WT) mouse dentate gyrus at postnatal days
      15, 21, 30, and 60. In contrast to neocortex, dendritic spine density was higher
      in Fmr1 KO mice across development. Interestingly, neither genotype showed
      specific phases of synaptogenesis or pruning, potentially explaining the
      phenotypic differences from neocortex. Similarly, although the KO mice showed a
      more immature morphological phenotype overall than WT (higher proportion of thin
      headed spines, lower proportion of mushroom and stubby spines), both genotypes
      showed gradual development, rather than impairments during specific phases of
      maturation. Finally, spine length showed a complex developmental pattern that
      differs from other brain regions examined, suggesting dynamic regulation by FMRP
      and other brain region-specific proteins. These findings shed new light on FMRP's
      role in development and highlight the need for new techniques to further
      understand the mechanisms by which FMRP affects synaptic maturation.

PMID- 20682301
TI  - The superior colliculus of the ferret: cortical afferents and efferent
      connections to dorsal thalamus.
AB  - By injecting both biotinylated and fluorescent dextran amines into the superior
      colliculus of the ferret we traced its afferent connections from the cerebral
      cortex and its projections to nuclei of the dorsal thalamus. All visual and
      auditory cortical areas had retrogradely labelled layer 5 pyramidal neurons
      projecting to the superior colliculus, with the highest density in areas 18 and
      21. Secondary somatosensory and motor cortical regions also projected to the
      superior colliculus. No retrograde labelling was observed in primary
      somatosensory, primary motor or prefrontal cortex. All visual dorsal thalamic
      nuclei received connections from the superior colliculus. Within the LGN, lamina
      C and the medial interlaminar nucleus (MIN) received dense afferents terminating
      with large labelled boutons. Within the lateral posterior nucleus (LP) a distinct
      band of moderately dense small, labelled boutons was observed, and within the
      pulvinar a broader and less dense region of small bouton labelling was observed.
      For the most part these connections are similar to those seen in the cat and
      other mammals, however, specific comparisons appear to delineate potential
      evolutionary trends related to complexity of the visual system.

PMID- 20682300
TI  - Synergistic protective effects of humanin and necrostatin-1 on hypoxia and
      ischemia/reperfusion injury.
AB  - Since several different pathways are involved in cerebral ischemia/reperfusion
      injury, combination therapy rather than monotherapy may be required for efficient
      neuroprotection. In this study, we examined the protective effects of an
      apoptosis inhibitor Gly(14)-humanin (HNG) and a necroptosis inhibitor necrostatin
      1 (Nec-1) on hypoxia/ischemia/reperfusion injury. Cultured mouse primary cortical
      neurons were incubated with Nec-1, HNG or both in a hypoxia chamber for 60 min.
      Cell viability was determined by MTS assay at 24h after oxygen-glucose
      deprivation (OGD) treatment. Mice underwent middle cerebral artery occlusion for
      75 min followed by 24h reperfusion. Mice were administered HNG and/or Nec-1
      (i.c.v.) at 4h after reperfusion. Neurological deficits were evaluated and the
      cerebral infarct volume was determined by TTC staining. Nec-1 or HNG alone had
      protective effects on OGD-induced cell death. Combined treatment with Nec-1 and
      HNG resulted in more neuroprotection than Nec-1 or HNG alone. Treatment with HNG
      or Nec-1 reduced cerebral infarct volume from 59.3 +/- 2.6% to 47.0 +/- 2.3% and
      47.1 +/- 1.5%, respectively. Combined treatment with HNG and Nec-1 improved
      neurological scores and decreased infarct volume to 38.6 +/- 1.5%. In summary, we
      demonstrated that the combination treatment of HNG and Nec-1 conferred
      synergistic neuroprotection on hypoxia/ischemia/reperfusion injury in vitro and
      in vivo. These findings provide a novel therapeutic strategy for the treatment of
      stroke by combining anti-apoptosis and anti-necroptosis therapy.

PMID- 20682302
TI  - Antinociceptive effects of histamine H3 receptor antagonist in the preclinical
      models of pain in rats and the involvement of central noradrenergic systems.
AB  - The histamine H(3) receptor is predominantly expressed in the central nervous
      system and plays a role in diverse physiological mechanisms. In the present
      study, the effects of GSK189254, a potent and selective H(3) antagonist, were
      characterized in preclinical pain models in rats. Systemic GSK189254 produced
      dose-dependent efficacy (ED(50)=0.77 mg/kg i.p.) in a rat model of
      monoiodoacetate (MIA) induced osteoarthritic (OA) pain as evaluated by hindlimb
      grip force. The role of H(3) receptors in regulating pain perception was further
      demonstrated using other structurally distinct H(3) antagonists. GSK189254 also
      displayed efficacy in a rat surrogate model indicative of central sensitization,
      namely phase 2 response of formalin-induced flinching, and attenuated tactile
      allodynia in the spinal nerve ligation model of neuropathic pain (ED(50)=1.5mg/kg
      i.p.). In addition, GSK189254 reversed persistent (CFA) (ED(50)=2.1mg/kg i.p,),
      whereas was ineffective in acute (carrageenan) inflammatory pain. When
      administered intrathecally (i.t.) to the lumbar spinal cord, GSK189254 produced
      robust effects in relieving the OA pain (ED(50)=0.0027 mg/kg i.t.). The systemic
      GSK189254 effect was completely reversed by the alpha-adrenergic receptor
      antagonist phentolamine (i.p. and i.t.) but not by the opioid receptor antagonist
      naloxone (i.p.). Furthermore, the i.t. GSK189254 effect was abolished when co
      administered with phentolamine (i.t.). These results suggest that the spinal cord
      is an important site of action for H(3) antagonism and the effect can be
      associated with activation of the noradrenergic system. Our data also provide
      support that selective H(3) antagonists may represent a class of agents for the
      treatment of pain disorders.

PMID- 20682303
TI  - Chronic green tea catechins administration prevents oxidative stress-related
      brain aging in C57BL/6J mice.
AB  - As the organism ages, production of reactive oxygen species (ROS) increases while
      antioxidants defense capability declines, leading to oxidative stress in critical
      cellular components, which further enhances ROS production. In the brain, this
      vicious cycle is more severe as brain is particularly vulnerable to oxidative
      damage. In our study, 14-month-old female C57BL/6J mice were orally administered
      0.05% green tea catechins (GTC, w/v) in drinking water for 6 months. We found
      that GTC supplementation prevented the decrease in total superoxide dismutase and
      glutathione peroxidase activities in serum as well as reduced the thiobarbituric
      acid reactive substances and protein carbonyl contents in the hippocampus of aged
      mice. The activation of transcriptional factor nuclear factor-kappa B and
      lipofuscin formation in pyramidal cells of hippocampal CA1 region, which are all
      related to oxidative stress, was also reduced after GTC treatment. We also found
      that long-term GTC treatment prevented age-related reductions of two
      representative post-synaptic proteins post-synaptic density 95 and N-methyl-d
      aspartate receptor 1 in the hippocampus. These results demonstrated that chronic
      0.05% green tea catechins administration may prevent oxidative stress related
      brain aging in female C57BL/6J mice.

PMID- 20682305
TI  - An NMDA antagonist inhibits light but not GRP-induced phase shifts when
      administered after the phase-shifting stimulus.
AB  - Brief light pulses or microinjection of gastrin-releasing peptide (GRP) into the
      third ventricle or near the suprachiasmatic nucleus (SCN) induce phase shifts of
      circadian rhythms during the subjective night. It has previously been reported
      that these effects are strongly influenced by the activation of N-methyl-d
      aspartate (NMDA) receptors and the availability of glutamate. We hypothesized
      that the photic signaling pathway in the SCN was dependent on glutamate
      neurotransmission even after the completion of a photic stimulus. Adult male
      Syrian hamsters equipped with a surgically implanted guide cannula aimed at the
      SCN region were housed in constant darkness until stable free-running rhythms of
      wheel-running activity were apparent. Light pulses administered in the early
      night induced phase delays of circadian rhythms which were attenuated by the co
      administration of (+/-)-2-amino-5-phosphonopentanoic acid (AP5), an NMDA
      antagonist. Microinjection of AP5 also inhibited light-induced shifts, to a
      lesser extent, immediately after and 15 min after, but not 30 min after the light
      pulse. A second experiment was designed to test whether AP5 would be able to
      attenuate GRP-induced shifts 15 min following microinjection of GRP. Phase shifts
      of animals that received microinjection of AP5 15 min after the administration of
      GRP were not different from those that received microinjection of GRP and
      vehicle. These data suggest that glutamate signaling remains necessary for a full
      photic response in the SCN even after the termination of the photic signal, but
      that this dependency ends once GRP-dependent signaling is complete.

PMID- 20682304
TI  - Diverse neurotoxicants converge on gene expression for neuropeptides and their
      receptors in an in vitro model of neurodifferentiation: effects of chlorpyrifos,
      diazinon, dieldrin and divalent nickel in PC12 cells.
AB  - Unrelated developmental neurotoxicants can produce similar neurobehavioral
      outcomes. We examined whether disparate agents affect neuromodulators that
      control numerous neurotransmitters and circuits, employing PC12 cells to explore
      the targeting of neuroactive peptides by organophosphates (chlorpyrifos,
      diazinon), an organochlorine (dieldrin) and a metal (Ni(2+)); we utilized
      microarrays to profile gene expression for the peptides and their receptors.
      Chlorpyrifos evoked robust upregulation of cholecystokinin, corticotropin
      releasing hormone, galanin, neuropeptide Y, neurotensin, preproenkephalin and
      tachykinin 1; this involved a critical period at the commencement of
      neurodifferentiation, since the effects were much less notable in
      undifferentiated PC12 cells. Diazinon targeted a similar but smaller repertoire
      of neuropeptide genes and the magnitude of the effects was also generally less.
      Surprisingly, dieldrin shared many of the same neuropeptide targets as the
      organophosphates and concordance analysis showed significant overlap among all
      three pesticides. However, dieldrin had more notable effects on neuropeptide
      receptors, and overlap between diazinon and dieldrin for the receptors led to a
      stronger resemblance of these two agents than of chlorpyrifos and dieldrin.
      Ni(2+) was unique, evoking upregulation of only one of the peptides affected by
      the other agents, while causing downregulation of several others. Nevertheless,
      there was still significant concordance between Ni(2+) and either diazinon or
      dieldrin, reflecting similarities toward the receptors. Our results show that
      neuropeptides are likely to be a prominent target for the developmental
      neurotoxicity of organophosphates and other neurotoxicants, and further, that the
      convergence of disparate agents on the same genes and pathways may contribute to
      similar neurobehavioral outcomes.

PMID- 20682306
TI  - Regional heterogeneity and age-related change in sub-regions of internal capsule
      evaluated by diffusion tensor imaging.
AB  - The internal capsule (IC) includes various fiber tracts supporting sensory, motor
      and cognitive abilities. Diffusion tensor imaging (DTI) is useful for the
      diagnosis of brain diseases related to IC. However, there is some risk of
      misdiagnosis when measuring diffusion parameters throughout the whole IC without
      knowledge of age-related changes, as the thin structure and branching in multiple
      directions must be expected to produce sub-regional differences. In this study,
      regional heterogeneity and age-related changes in water diffusion parameters were
      evaluated in sub-regions of IC. The IC region-of-interest (ROI) was first thinned
      to reduce contamination from surrounding tissues and then morphologically divided
      into three regions: anterior limb (AL), genu and posterior limb (PL). To address
      the branching of PL, a procedure was applied to divide the thinned PL ROI into 10
      equally-spaced positions. Estimates of fractional anisotropy (FA), mean
      diffusivity (MD), and longitudinal (lambda(L)) and transversal (lambda(T))
      eigenvalues showed age-related and location-dependent variation in AL, genu and
      PL ROIs and at the 10 equally-spaced positions of PL. Simultaneous decrease of
      lambda(L) and increase of lambda(T) resulting in decrease of FA and steady MD
      with aging were observed. This might be caused by age-related atrophy of main
      fibers such as the pyramidal tract, possibly resulting in an increase in the
      relative signal contribution of some crossing fibers in each pixel. Evaluation
      using eigenvalues (lambda(L) and lambda(T)), as well as FA and MD, may provide
      important information towards understanding age-related changes and may also be
      useful for clinical diagnosis of diseased IC.

PMID- 20682307
TI  - Differential effects of antipsychotic and antidepressant drugs on neurogenic
      regions in rats.
AB  - Increased neurogenesis in the hippocampus and subventricular zone (SVZ) of the
      brain of animals has been demonstrated following administration of several
      psychotropic medications. Such changes are thought to regenerate tissues and
      contribute to the beneficial effects of the medications. This study sought to
      determine if another neurogenic tissue, the peripheral olfactory epithelium (OE),
      might also exhibit changes after treatment with psychotropic medications. Young
      adult male rats were treated with risperidone and paliperidone, atypical
      antipsychotic medications; fluoxetine, a selective serotonin reuptake inhibitor
      (SSRI) antidepressant; and diluent control for 28days via drinking water.
      Bromodeoxyuridine (BrdU) was injected to label dividing cells and positive cells
      were quantified in the OE, cortical SVZ, and dentate gyrus (DG) of the
      hippocampus. In the first of two studies, paliperidone and risperidone treatment
      (at 1mg/kg/day) resulted in increased numbers over controls of BrdU positive
      cells in the OE. In the second study, examining OE, SVZ and DG in the same
      animal, paliperidone, but not risperidone or fluoxetine (0.6 mg/kg/day) resulted
      in increased cells in the OE and posterior SVZ. However, fluoxetine, but not
      paliperidone or risperidone treatment increased BrdU positive cells in the DG.
      These results show that psychotropic drug-induced cell proliferation occurs in
      the OE and parallels changes in the SVZ but not DG. Thus, the peripheral OE can
      serve as a proxy for certain psychotropic drug-induced actions on SVZ brain cell
      proliferation. This olfactory model can be employed in human research as a method
      to explore the neurogenesis effects of various pharmacologic treatments of
      neuropsychiatric disorders.

PMID- 20682308
TI  - The combined effects of the BDNF and GSK3B genes modulate the relationship
      between negative life events and major depressive disorder.
AB  - For major depressive disorder (MDD), BDNF and GSK3B are logical candidate genes
      and an interaction between BDNF polymorphism and negative life events has been
      observed. Our previous study revealed that a gene-gene interaction among BDNF and
      GSK3B may confer the risk of MDD. In the present study, we hypothesized a gene
      environment interaction between the BDNF-GSK3B combination and negative life
      events in the risk for developing MDD. To test this hypothesis, we conducted a
      case-control study in a northern Han Chinese population. A total of 404 patients
      with MDD and 388 age- and gender-matched control subjects were recruited.
      Negative life events and objective social supports were assessed using standard
      rating scales. Three polymorphisms of BDNF and GSK3B genes were identified by
      sequencing. Gene-environment interactions were analyzed by generalized
      multifactor dimensionality reduction (GMDR). Under a dominant model, we observed
      a potential association between the GSK3B rs6782799 and MDD (P=0.07), a
      significant three-way interaction among BDNF rs6265, GSK3B rs6782799, and
      negative life events (corrected P-value, 0.011-0.012; cross-validation
      consistency, 7; prediction error, 0.4349). To our knowledge, this is the first
      report of evidence that the BDNF-GSK3B interaction may modify the relationship
      between negative life events and MDD in the Chinese population.

PMID- 20682309
TI  - Differential effects of testosterone and TGF-beta3 on endocytic vesicle-mediated
      protein trafficking events at the blood-testis barrier.
AB  - The intricate interaction between protein endocytosis, transcytosis, recycling
      and endosome- or ubiquitin-mediated protein degradation determines the junction
      integrity in epithelial cells including Sertoli cells at the blood-testis barrier
      (BTB). Studies have shown that androgens and cytokines (e.g., TGF-beta3) that are
      known to promote and disrupt BTB integrity, respectively, accelerate protein
      endocytosis at the BTB. We hypothesized that testosterone-induced endocytosed
      proteins are transcytosed and recycled back to the Sertoli cell surface, whereas
      cytokine-induced endocytosed proteins are degraded so that androgens and
      cytokines have opposing effects on BTB integrity. Herein, we report that both
      testosterone and TGF-beta3 induced the steady-state level of clathrin, an
      endocytic vesicle protein. Testosterone and TGF-beta3 also induced the
      association between internalized occludin (a BTB integral membrane protein) and
      clathrin, as well as early endosome antigen-1 (EEA-1). Interestingly,
      testosterone, but not TGF-beta3, also induced the levels of proteins that
      regulate protein transcytosis (e.g., caveolin-1) and recycling (e.g., Rab11), and
      their association with internalized occludin and N-cadherin from the cell
      surface. In contrast, TGF-beta3, but not testosterone, induced the level of
      ubiquitin-conjugating enzyme E2 J1 (Ube2j1), a protein crucial to the
      intracellular protein degradation pathway, and its association with internalized
      occludin. Based on these findings and recent reports in the field, we hypothesize
      that the concerted effects of testosterone and TGF-beta3 likely facilitate the
      transit of preleptotene spermatocytes at the BTB while maintaining the
      immunological barrier in that testosterone induces the assembly of "new" tight
      junction (TJ)-fibrils below migrating spermatocytes via protein transcytosis and
      recycling before cytokines induce the disassembly of "old" TJ-fibrils above
      spermatocytes via endocytic vesicle-mediated degradation of internalized
      proteins. This thus provides a unique mechanism in the testis to facilitate the
      transit of preleptotene spermatocytes, many of which are connected in "clones"
      via cytoplasmic bridges, at the BTB while maintaining the immunological barrier
      during stage VIII of the seminiferous epithelial cycle of spermatogenesis.

PMID- 20682310
TI  - Targeting individual calpain isoforms for neuroprotection.

PMID- 20682311
TI  - Fission yeast telomeres forecast the end of the crisis.
AB  - Recent years have placed fission yeast at the forefront of telomere research, as
      this organism combines a high level of conservation with human telomeres and
      precise genetic manipulability. Here we highlight some of the latest knowledge of
      fission yeast telomere maintenance and dysfunction, and illustrate how principles
      arising from fission yeast research are raising novel questions about telomere
      plasticity and function in all eukaryotes.

PMID- 20682312
TI  - Oxazolone-induced over-expression of focal adhesion kinase in colonic epithelial
      cells of colitis mouse model.
AB  - We examined the change of protein tyrosine kinases (PTKs) expression levels in
      colonic epithelial cells isolated from mice in which colitis was induced by
      oxazolone administration, using the monoclonal antibody YK34, which cross-reacts
      with a wide variety of PTKs. We identified focal adhesion kinase (FAK) and found
      the expression level increased due to the induction of colitis. Furthermore, we
      found that there was a positive correlation between FAK expression and the
      severity of colitis. Also, FAK expression localized in the colonic epithelium but
      not in the lamina propria, implying FAK functions in epithelial cells during
      colitis formation and/or wound repairing.

PMID- 20682313
TI  - Induction of endosomal/lysosomal pathways in differentiating osteoblasts as
      revealed by combined proteomic and transcriptomic analyses.
AB  - We have analyzed proteome changes associated with bone-forming osteoblast
      differentiation by quantitative differential proteomic and transcriptomic
      analyses using in vitro differentiation model. Sixty nine proteins were found up
      regulated (>2-fold) and 18 were down-regulated (<0.5-fold) at protein level. The
      mRNA levels of these proteins were then analyzed by quantitative real-time PCR
      combined with clustering analysis. The most prominent cluster with increased
      protein and mRNA levels contains endosomal and lysosomal proteins, demonstrating
      the drastic induction of degradative endosomal/lysosomal pathways in osteoblasts.
      Osteoblasts, therefore, are involved not only in the synthesis but also in the
      turnover of the extracellular matrix proteins such as collagens.

PMID- 20682314
TI  - A distinct subset of podoplanin (gp38) expressing F4/80+ macrophages mediate
      phagocytosis and are induced following zymosan peritonitis.
AB  - Macrophages are important tissue resident cells that regulate the dynamics of
      inflammation. However, they are strikingly heterogeneous. During studies looking
      at podoplanin (gp38) expression on stromal cells in the murine spleen and
      peritoneal cavity we unexpectedly discovered that podoplanin was expressed on a
      subset of F4/80(+) macrophages; a subset which we have termed fibroblastic
      macrophages (FM). These cells function as phagocytes in vitro as measured by bead
      mediated phagocytosis assays. FM also exist at high frequency in the peritoneal
      cavity and in zymosan induced peritonitis in vivo. These FM represent a unique
      subgroup of F4/80(+) macrophages and their presence in the inflamed peritoneum
      suggests that they play a role in zymosan induced peritonitis.

PMID- 20682315
TI  - Episodic sitewise positive selection on the signal recognition particle protein
      Ffh in Actinobacteria.
AB  - In this work, we report a case of episodic sitewise positive selection acting on
      the highly conserved SRP protein Ffh in Actinobacteria. An elevated non
      synonymous to synonymous mutation ratio (omega) was observed along the non
      terminal branches of the species tree, which contained 11 Actinobacteria species,
      where positively selected residues were frequently observed within the signal
      sequence-binding domain. Together with the estimated lineage-specific omega
      ratios for several core components in the major protein translocation systems,
      our data suggest that this positive selection might be partially driven by the
      diversification of signal sequences.

PMID- 20682316
TI  - Molecular determinants of the interactions between SRC-1 and LXR/RXR
      heterodimers.
AB  - Liver X receptor (LXR)/retinoid X receptor (RXR) heterodimers have been shown to
      perform critical functions in cholesterol and lipid metabolism. Here, we have
      conducted a comparative analysis of the contributions of LXR and RXR binding to
      steroid receptor coactivator-1 (SRC-1), which contains three copies of the NR
      box. We demonstrated that the coactivator-binding surface of LXR, but not that of
      RXR, is critically important for physical and functional interactions with SRC-1,
      thereby confirming that RXR functions as an allosteric activator of SRC-1-LXR
      interaction. Notably, we identified NR box-2 and -3 as the essential binding
      targets for the SRC-1-induced stimulation of LXR transactivity, and observed the
      competitive in vitro binding of NR box-2 and -3 to LXR.

PMID- 20682317
TI  - Hypomethylation of the IGF2 DMR in colorectal tumors, detected by bisulfite
      pyrosequencing, is associated with poor prognosis.
AB  - BACKGROUND & AIMS: The insulin-like growth factor 2 (IGF2) gene is normally
      imprinted. Constitutive loss of imprinting (LOI) of IGF2 has been associated with
      increased risks of colon cancer and adenoma, indicating its role in
      carcinogenesis. The conventional LOI assay relies on a germline polymorphism to
      distinguish between 2 allelic expression patterns but results in many
      uninformative cases. IGF2 LOI correlates with hypomethylation at the
      differentially methylated region (DMR)-0. An assay for methylation of the DMR0
      could overcome the limitations of the conventional IGF2 LOI assay. METHODS: We
      measured methylation at the IGF2 DMR0 using a bisulfite-pyrosequencing assay with
      1178 paraffin-embedded colorectal cancer tissue samples from 2 prospective cohort
      studies. A Cox proportional hazard model was used to calculate mortality hazard
      ratio (HR); calculations were adjusted for microsatellite instability; the CpG
      island methylator phenotype; LINE-1 methylation; and KRAS, BRAF, and PIK3CA
      mutations. RESULTS: Methylation at the IGF2 DMR0 was successfully measured in
      1105 (94%) of 1178 samples. Colorectal tumors had significantly less methylation
      at the DMR0 compared with matched, normal colonic mucosa (P < .0001; N = 51).
      Among 1033 patients eligible for survival analysis, hypomethylation of the IGF2
      DMR0 was significantly associated with higher overall mortality (log-rank P =
      .0006; univariate HR, 1.41; 95% confidence interval, 1.16-1.71; P = .0006;
      multivariate HR, 1.33; 95% confidence interval, 1.08-1.63; P = .0066).
      CONCLUSIONS: A bisulfite-pyrosequencing assay to measure methylation of the IGF2
      DMR0 is robust and applicable to paraffin-embedded tissue. IGF2 DMR0
      hypomethylation in colorectal tumor samples is associated with shorter survival
      time, so it might be developed as a prognostic biomarker.

PMID- 20682318
TI  - Granulin-epithelin precursor and ATP-dependent binding cassette (ABC)B5 regulate
      liver cancer cell chemoresistance.
AB  - BACKGROUND & AIMS: Chemotherapy is used to treat unresectable liver cancer with
      marginal efficacy; this might result from hepatic cancer cells with stem cell and
      chemoresistant features. Gene expression profiling studies have shown that
      hepatic cancer cells express granulin-epithelin precursor (GEP); we investigated
      its role in hepatic cancer stem cell functions and chemoresistance. METHODS: The
      effects of GEP and drug transporter signaling on chemoresistance were
      investigated in hepatic cancer stem cells. We analyzed the expression patterns of
      142 clinical samples from liver tumors, adjacent nontumorous liver tissue, and
      liver tissue from patients who did not have cancer. RESULTS: GEP regulated the
      expression of the adenosine triphosphate-dependent binding cassette (ABC)B5 drug
      transporter in liver cancer cells. Chemoresistant cells that expressed GEP had
      increased levels of ABCB5; suppression of ABCB5 sensitized the cells to
      doxorubicin uptake and apoptosis. Most cells that expressed GEP and ABCB5 also
      expressed the hepatic cancer stem cell markers CD133 and EpCAM; blocking ABCB5
      reduced their expression. Expression levels of GEP and ABCB5 were correlated in
      human liver tumor samples. ABCB5 levels were increased in liver cancer cells
      compared with nontumor liver tissue from patients with cirrhosis or hepatitis, or
      normal liver tissue. ABCB5 expression was associated with the recurrence of
      hepatocellular carcinoma after partial hepatectomy. CONCLUSIONS: Expression of
      GEP and ABCB5 in liver cancer stem cells is associated with chemoresistance and
      reduced survival times of patients with hepatocellular carcinoma. Reagents
      designed to target these proteins might be developed as therapeutics and given in
      combination with chemotherapy to patients with liver cancer.

PMID- 20682319
TI  - BMP6 treatment compensates for the molecular defect and ameliorates
      hemochromatosis in Hfe knockout mice.
AB  - BACKGROUND & AIMS: Abnormal hepcidin regulation is central to the pathogenesis of
      HFE hemochromatosis. Hepatic bone morphogenetic protein 6 (BMP6)-SMAD signaling
      is a main regulatory mechanism controlling hepcidin expression, and this pathway
      was recently shown to be impaired in Hfe knockout (Hfe(-/-)) mice. To more
      definitively determine whether HFE regulates hepcidin expression through an
      interaction with the BMP6-SMAD signaling pathway, we investigated whether hepatic
      Hfe overexpression activates the BMP6-SMAD pathway to induce hepcidin expression.
      We then investigated whether excess exogenous BMP6 administration overcomes the
      BMP6-SMAD signaling impairment and ameliorates hemochromatosis in Hfe(-/-) mice.
      METHODS: The BMP6-SMAD pathway and the effects of neutralizing BMP6 antibody were
      examined in Hfe transgenic mice (Hfe Tg) compared with wild-type (WT) mice. Hfe(
      /-) and WT mice were treated with exogenous BMP6 and analyzed for hepcidin
      expression and iron parameters. RESULTS: Hfe Tg mice exhibited hepcidin excess
      and iron deficiency anemia. Hfe Tg mice also exhibited increased hepatic BMP6
      SMAD target gene expression compared with WT mice, whereas anti-BMP6 antibody
      administration to Hfe Tg mice improved the hepcidin excess and iron deficiency.
      In Hfe(-/-) mice, supraphysiologic doses of exogenous BMP6 improved hepcidin
      deficiency, reduced serum iron, and redistributed tissue iron to appropriate
      storage sites. CONCLUSIONS: HFE interacts with the BMP6-SMAD signaling pathway to
      regulate hepcidin expression, but HFE is not necessary for hepcidin induction by
      BMP6. Exogenous BMP6 treatment in mice compensates for the molecular defect
      underlying Hfe hemochromatosis, and BMP6-like agonists may have a role as an
      alternative therapeutic strategy for this disease.

PMID- 20682320
TI  - Budesonide is effective in adolescent and adult patients with active eosinophilic
      esophagitis.
AB  - BACKGROUND & AIMS: Eosinophilic esophagitis (EoE) is a chronic inflammatory
      disease of the esophagus characterized by dense tissue eosinophilia; it is
      refractory to proton pump inhibitor therapy. EoE affects all age groups but most
      frequently individuals between 20 and 50 years of age. Topical corticosteroids
      are effective in pediatric patients with EoE, but no controlled studies of
      corticosteroids have been reported in adult patients. METHODS: We performed a
      randomized, double-blind, placebo-controlled trial to evaluate the effect of oral
      budesonide (1 mg twice daily for 15 days) in adolescent and adult patients with
      active EoE. Pretreatment and posttreatment disease activity was assessed
      clinically, endoscopically, and histologically. The primary end point was reduced
      mean numbers of eosinophils in the esophageal epithelium (number per high-power
      field [hpf] = esophageal eosinophil load). Esophageal biopsy and blood samples
      were analyzed using immunofluorescence and immunoassays, respectively, for
      biomarkers of inflammation and treatment response. RESULTS: A 15-day course of
      therapy significantly decreased the number of eosinophils in the esophageal
      epithelium in patients given budesonide (from 68.2 to 5.5 eosinophils/hpf; P <
      .0001) but not in the placebo group (from 62.3 to 56.5 eosinophils/hpf; P = .48).
      Dysphagia scores significantly improved among patients given budesonide compared
      with those given placebo (5.61 vs 2.22; P < .0001). White exudates and red
      furrows were reversed in patients given budesonide, based on endoscopy
      examination. Budesonide, but not placebo, also reduced apoptosis of epithelial
      cells and molecular remodeling events in the esophagus; no serious adverse events
      were observed. CONCLUSIONS: A 15-day course of treatment with budesonide is well
      tolerated and highly effective in inducing a histologic and clinical remission in
      adolescent and adult patients with active EoE.

PMID- 20682321
TI  - Stress signaling in the methionine-choline-deficient model of murine fatty liver
      disease.
AB  - BACKGROUND & AIMS: Stress signaling, both within and outside the endoplasmic
      reticulum, has been linked to metabolic dysregulation and hepatic steatosis.
      Methionine-choline-deficient (MCD) diets cause severe fatty liver disease and
      have the potential to cause many types of cellular stress. The purpose of this
      study was to characterize hepatic stress in MCD-fed mice and explore the
      relationship between MCD-mediated stress and liver injury. METHODS: Stress
      signaling was examined in mice fed MCD formulas for 4-21 days. Signaling also was
      evaluated in mice fed MCD formulas supplemented with clofibrate, which inhibits
      hepatic triglyceride accumulation. The role of the pro-apoptotic stress protein
      C/EBP homologous protein (CHOP) in MCD-mediated liver injury was assessed by
      comparing the responses of wild-type and CHOP-deficient mice to an MCD diet.
      RESULTS: MCD feeding caused steatohepatitis coincident with the activation of
      cJun N-terminal kinase and caspase-12. In contrast, MCD feeding did not activate
      inositol-requiring protein-1 and actually suppressed the expression of X-box
      protein-1s. MCD feeding caused weak stimulation of double-stranded RNA-activated
      protein kinase-like endoplasmic reticulum-resident kinase, but robust activation
      of general control nonderepressible-2, followed by the phosphorylation of
      eukaryotic initiating factor-2alpha and induction of CHOP. Clofibrate eliminated
      MCD-mediated hepatic steatosis but did not inhibit diet-induced stress. CHOP
      deficiency did not alleviate, and in fact worsened, MCD-mediated liver disease.
      CONCLUSIONS: MCD feeding causes an integrated stress response in the liver rather
      than a classic unfolded protein response. This stress response does not by itself
      lead to liver injury. CHOP, despite its identity as a mediator of stress-related
      cell death, does not play a central role in the pathogenesis of MCD-mediated
      liver disease.

PMID- 20682322
TI  - Loss of Indian Hedgehog activates multiple aspects of a wound healing response in
      the mouse intestine.
AB  - BACKGROUND & AIMS: Indian Hedgehog (Ihh) is expressed by the differentiated
      epithelial cells of the small intestine and signals to the mesenchyme where it
      induces unidentified factors that negatively regulate intestinal epithelial
      precursor cell fate. Recently, genetic variants in the Hh pathway have been
      linked to the development of inflammatory bowel disease. METHODS: We deleted Ihh
      from the small intestinal epithelium in adult mice using Cyp1a1-CreIhh(fl/fl)
      conditional Ihh mutant mice. Intestines were examined by immunohistochemistry, in
      situ hybridization, and real-time polymerase chain reaction. RESULTS: Deletion of
      Ihh from the intestinal epithelium initially resulted in a proliferative response
      of the intestinal epithelium with lengthening and fissioning of crypts and
      increased Wnt signaling. The epithelial proliferative response was associated
      with loss of bone morphogenetic protein and Activin signaling from the epithelium
      of the villus and crypts, respectively. At the same stage we observed a
      substantial influx of fibroblasts and macrophages into the villus core with
      increased mesenchymal transforming growth factor-beta signaling and deposition of
      extracellular matrix proteins. Prolonged loss of Ihh resulted in progressive
      leukocyte infiltration of the crypt area, blunting and loss of villi, and the
      development of intestinal fibrosis. CONCLUSIONS: Loss of Ihh initiates several
      events that are characteristic of an intestinal wound repair response. Prolonged
      loss resulted in progressive inflammation, mucosal damage, and the development of
      intestinal fibrosis. Ihh is a signal derived from the superficial epithelial
      cells that may act as a critical indicator of epithelial integrity.

PMID- 20682323
TI  - Intravascular transfer contributes to postprandial increase in numbers of very
      low-density hepatitis C virus particles.
AB  - BACKGROUND & AIMS: The physical association of hepatitis C virus (HCV) particles
      with lipoproteins in plasma results in distribution of HCV in a broad range of
      buoyant densities. This association is thought to increase virion infectivity by
      mediating cell entry via lipoprotein receptors. We sought to determine if factors
      that affect triglyceride-rich lipoprotein (TRL) metabolism alter the density and
      dynamics of HCV particles in the plasma of patients with chronic HCV infection.
      METHODS: Fasting patients (n = 10) consumed a high-fat milkshake; plasma was
      collected and fractionated by density gradients. HCV- RNA was measured in the
      very-low-density fraction (VLDF, d < 1.025 g/mL) before and at 7 serial time
      points postprandially. RESULTS: The amount of HCV RNA in the VLDF (HCV(VLDF))
      increased a mean of 26-fold, peaking 180 minutes after the meal (P < .01).
      Quantification of HCV RNA throughout the density gradient fractions revealed that
      HCV(VLDF) rapidly disappeared, rather than migrating into the adjacent density
      fraction. Immuno-affinity separation of the VLDF, using antibodies that recognize
      apolipoprotein B-100 and not apolipoprotein B-48, showed that HCV(VLDF) is
      composed of chylomicron- and VLDL-associated HCV particles; peaking 120 and 180
      minutes after the meal, respectively. Plasma from fasting HCV-infected patients
      mixed with uninfected plasma increased the quantity of HCV(VLDF), compared with
      that mixed with phosphate-buffered saline, showing extracellular assembly of
      HCV(VLDF). CONCLUSIONS: Dietary triglyceride alters the density and dynamics of
      HCV in plasma. The rapid clearance rate of HCV(VLDF) indicates that association
      with TRL is important for HCV infectivity. HCV particles, such as exchangeable
      apolipoproteins, appear to reassociate with TRLs in the vascular compartment.

PMID- 20682324
TI  - Prognostic importance of the cause of renal failure in patients with cirrhosis.
AB  - BACKGROUND & AIMS: The prognostic value of the different causes of renal failure
      in cirrhosis is not well established. This study investigated the predictive
      value of the cause of renal failure in cirrhosis. METHODS: Five hundred sixty-two
      consecutive patients with cirrhosis and renal failure (as defined by serum
      creatinine > 1.5 mg/dL on 2 successive determinations within 48 hours)
      hospitalized over a 6-year period in a single institution were included in a
      prospective study. The cause of renal failure was classified into 4 groups: renal
      failure associated with bacterial infections, renal failure associated with
      volume depletion, hepatorenal syndrome (HRS), and parenchymal nephropathy. The
      primary end point was survival at 3 months. RESULTS: Four hundred sixty-three
      patients (82.4%) had renal failure that could be classified in 1 of 4 groups. The
      most frequent was renal failure associated with infections (213 cases; 46%),
      followed by hypovolemia-associated renal failure (149; 32%), HRS (60; 13%), and
      parenchymal nephropathy (41; 9%). The remaining patients had a combination of
      causes or miscellaneous conditions. Prognosis was markedly different according to
      cause of renal failure, 3-month probability of survival being 73% for parenchymal
      nephropathy, 46% for hypovolemia-associated renal failure, 31% for renal failure
      associated with infections, and 15% for HRS (P < .0005). In a multivariate
      analysis adjusted for potentially confounding variables, cause of renal failure
      was independently associated with prognosis, together with MELD score, serum
      sodium, and hepatic encephalopathy at time of diagnosis of renal failure.
      CONCLUSIONS: A simple classification of patients with cirrhosis according to
      cause of renal failure is useful in assessment of prognosis and may help in
      decision making in liver transplantation.

PMID- 20682325
TI  - Algebraic connectivity may explain the evolution of gene regulatory networks.
AB  - Gene expression is a result of the interplay between the structure, type,
      kinetics, and specificity of gene regulatory interactions, whose diversity gives
      rise to the variety of life forms. As the dynamic behavior of gene regulatory
      networks depends on their structure, here we attempt to determine structural
      reasons which, despite the similarities in global network properties, may explain
      the large differences in organismal complexity. We demonstrate that the algebraic
      connectivity, the smallest non-trivial eigenvalue of the Laplacian, of the
      directed gene regulatory networks decreases with the increase of organismal
      complexity, and may therefore explain the difference between the variety of
      analyzed regulatory networks. In addition, our results point out that, for the
      species considered in this study, evolution favours decreasing concentration of
      strategically positioned feed forward loops, so that the network as a whole can
      increase the specificity towards changing environments. Moreover, contrary to the
      existing results, we show that the average degree, the length of the longest
      cascade, and the average cascade length of gene regulatory networks cannot
      recover the evolutionary relationships between organisms. Whereas the dynamical
      properties of special subnetworks are relatively well understood, there is still
      limited knowledge about the evolutionary reasons for the already identified
      design principles pertaining to these special subnetworks, underlying the global
      quantitative features of gene regulatory networks of different organisms. The
      behavior of the algebraic connectivity, which we show valid on gene regulatory
      networks extracted from curated databases, can serve as an additional
      evolutionary principle of organism-specific regulatory networks.

PMID- 20682326
TI  - Comments on: De Luca C., et al.: Biological definition of multiple chemical
      sensitivity... Toxicol Appl Pharm.l epub ahead of publication, 2010, 20 April.

PMID- 20682327
TI  - Highly purified hexachlorobenzene induces cytochrome P4501A in primary cultures
      of chicken embryo hepatocytes.
AB  - Some uncertainty exists regarding the purity of hexachlorobenzene (HCB) used in
      past toxicity studies. It has been suggested that reported toxic and biochemical
      effects initially attributed to HCB exposure may have actually been elicited by
      contamination of HCB by polychlorinated dibenzo-p-dioxins (PCDDs) and
      polychlorinated dibenzofurans (PCDFs). Herein, primary cultures of chicken embryo
      hepatocytes (CEH) were used to compare the potencies of two lots of reagent-grade
      hexachlorobenzene (HCB-old [HCB-O] and HCB-new [HCB-N]), highly purified HCB (HCB
      P) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as inducers of ethoxyresorufin
      O-deethylase (EROD) activity, cytochrome P4501A4 (CYP1A4) messenger ribonucleic
      acid (mRNA) and CYP1A5 mRNA. The study also compared the EROD- and CYP1A4/5 mRNA
      inducing potencies of HCB to the potencies of two mono-ortho substituted
      polychlorinated biphenyls (PCBs), 2,3,3',4,4'-pentachlorobiphenyl (PCB 105) and
      2,3'4,4',5-pentachlorobiphenyl (PCB 118). HCB-O, HCB-N and HCB-P all induced EROD
      activity and up-regulated CYP1A4 and CYP1A5 mRNAs. Induction was not caused by
      contamination of HCB with PCDDs or PCDFs. Based upon a comparison of the EC(50)
      and EC(threshold) values for EROD and CYP1A4/5 mRNA concentration-response
      curves, the potency of HCB relative to the potency of TCDD was 0.0001, and was
      similar to that of PCB 105 and PCB 118. The maximal EROD activity and CYP1A4/5
      mRNA expression differed greatly between HCB and TCDD, and may contribute to an
      overestimation of the ReP value calculated for highly purified HCB.

PMID- 20682328
TI  - The contribution of scene context on change detection performance.
AB  - The gist of a visual scene is perceived in a fraction of a second but in change
      detection tasks subjects typically need several seconds to find the changing
      object in a visual scene. Here, we report influences of scene context on change
      detection performance. Scene context manipulations consisted of scene inversion,
      scene jumbling, where the images were cut into 24 pieces and randomly recombined,
      and scene configuration scrambling, where the arrangement of the objects in the
      scene was randomized. Reaction times, where significantly lower in images with
      normal scene context. We conclude that scene context structures scene perception.

PMID- 20682329
TI  - Sound can prolong the visible persistence of moving visual objects.
AB  - An abrupt change in a visual attribute (size) of apparently moving visual stimuli
      extends the time the changed stimuli is visible even after its physical
      termination (visible persistence). In this study, we show that elongation of
      visible persistence is enhanced by an abrupt change in an attribute (frequency)
      of the sounds presented along with the size-changed apparently moving visual
      stimuli. This auditory effect disappears when sounds are not associated with the
      visual stimuli. These results suggest that auditory attribute change can
      contribute to the establishment of a new object representation and that object
      level audio-visual interactions can occur in motion perception.

PMID- 20682330
TI  - Tracking of sedentary behaviours of young people: a systematic review.
AB  - OBJECTIVE: To review the empirical evidence concerning the strength of tracking
      of sedentary behaviours from childhood and adolescence. METHODS: Published
      English language studies were located from computerised and manual searches in
      2009. Included studies were prospective, longitudinal studies with at least one
      sedentary behaviour for at least two time-points, with tracking coefficients
      reported, and included children (aged 3-11 years) and adolescents (12-18 years)
      at baseline. RESULTS: Based on data from 21 independent samples, tracking
      coefficients (r) ranged from 0.08 (over 16 years) to 0.73 (over 2 years) for TV
      viewing, from 0.18 (boys over 3 years) to 0.52 (over 2 years) for electronic
      game/computer use, from 0.16 (girls over 4 years) to 0.65 (boys over 2 years) for
      total screen time, and from -0.15 (boys over 2 years) to 0.48 (over 1 year) for
      total sedentary time. Study follow-up periods ranged from 1 to up to 27 years,
      and tracking coefficients tended to be higher with shorter follow-ups.
      CONCLUSIONS: Sedentary behaviours track at moderate levels from childhood or
      adolescence. Data suggest that sedentary behaviours may form the foundation for
      such behaviours in the future and some may track slightly better than physical
      activity.

PMID- 20682331
TI  - Automatic reconstruction of the mouse segmentation network from an experimental
      evidence database.
AB  - Mammalian vertebrae, ribs, body wall musculature and back skin develop from
      repetitive embryonic tissues called somites. The development of somites depends
      on the molecular oscillations of the products of so-called cyclic genes. The
      underlying network involves the Wnt, Fgf/Mapk, Notch signaling pathways and the T
      box genes. The discovery of this network is based on genetic interactions.
      Because of regulatory feedbacks and cross-regulation between pathways, it is
      often difficult to intuitively identify direct molecular interactions underlying
      genetic interactions. To address this problem, we developed a method based on a
      database and graph theory algorithms. We first encoded genetic and non-genetic
      experiments in a relational database. Next, we built a reference network with the
      data from non-genetic experiments and the KEGG pathway database. Then, we
      computed the shortest path between the nodes for each genetic interaction in the
      reference network to propose direct molecular interactions. The resulting network
      is the largest computational representation of the mammalian segmentation network
      to date with 36 nodes and 57 interactions. In some instances, a number of genetic
      interactions could be explained by adding a single link to the reference network,
      which leads to experimentally testable hypotheses. Two examples of such
      predictions are the direct transcriptional regulation of Dll3 and Fgf8 genes by
      the Rbpj and Ctnnb1 products, respectively. Furthermore, the computed shortest
      paths suggest that cross-talks from the Wnt to the Fgf/Mapk and Notch pathways
      might be mediated by the Dvl genes. This method can be applied in any system
      where gene expression changes are observed as a response to some gene
      perturbation, for instance in cancer cells.

PMID- 20682332
TI  - Cloning and distribution of Ca2+-activated K+ channels in lobster Panulirus
      interruptus.
AB  - Large conductance Ca(2+)-activated potassium (BK) channels play important roles
      in controlling neuronal excitability. We cloned the PISlo gene encoding BK
      channels from the spiny lobster, Panulirus interruptus. This gene shows 81-98%
      sequence identity to Slo genes previously found in other organisms. We isolated a
      number of splice variants of the PISlo cDNA within Panulirus interruptus nervous
      tissue. Sequence analysis indicated that there are at least seven alternative
      splice sites in PISlo, each with multiple alternative segments. Using
      immunohistochemistry, we found that the PISlo proteins are distributed in the
      synaptic neuropil, axon and soma of stomatogastric ganglion (STG) neurons.

PMID- 20682333
TI  - Associations between the tumor necrosis factor alpha gene (-308G->A) and event
      related potential indices of attention and mental rotation.
AB  - The tumor necrosis factor alpha (TNF-alpha) is a cytokine that exerts
      neuroprotective and neurodegenerative effects. While some research suggests
      enhancing effects of the TNF-alpha gene (TNF-alpha -308G->A) on cognitive
      function, further research is needed to clarify the association between the TNF
      alpha gene and specific areas of cognitive performance including their
      neurophysiological correlates. In this study we examine association of the TNF
      alpha -308G->A single nucleotide polymorphism (rs1800629) with attention and
      mental rotation performance in an event-related potential (ERP) study in healthy
      participants (n=67). The results show that carriers of the -308 A allele display
      elevated attentional processes (i.e. a stronger N1) as compared to the GG
      genotype group. Mental rotation performance varied across genotypes when demands
      on mental rotation were high. Here, carriers of the -308 A allele performed
      better than the GG genotype group. This is paralleled by the neurophysiological
      data showing genotype-dependent variations in parietal positivities only under
      the condition of high demands on mental rotation. The finding of enhanced
      attentional and mental rotation performance in A allele carriers supports recent
      findings that the A allele of this single nucleotide polymorphism (SNP) enhances
      cognitive performance on a general measure of cognitive processing speed.

PMID- 20682335
TI  - Mechanism-based alternative monitoring of endoplasmic reticulum stress by 8-keto
      trichothecene mycotoxins using human intestinal epithelial cell line.
AB  - Type B 8-keto trichothecenes are muco-active mycotoxins that are notable
      contaminants in cereal-based food stuffs. Epithelial responses are of primary
      concern during gastrointestinal exposure in human and animal intoxications.
      Therefore, optimized biomarkers to assess the specific action of trichothecenes
      on the human epithelial barrier are needed. In the present study, 8-keto
      trichothecenes were tested to trigger endoplasmic reticulum (ER) stresses that
      are evident as alteration of eukaryotic initiation factors 2alpha phosphorylation
      and other ER stress markers in human intestinal epithelial cells. Based on the ER
      stress-inducing activity of 8-keto trichothecenes, we developed a bio-monitoring
      method using intestinal epithelial cells constitutively expressing secretory
      alkaline phosphatase (SEAP) reporter, which can be used as a sensitive and
      selective indicator for monitoring ER stress in the epithelial barrier. Type B 8
      keto trichothecenes suppressed the release of SEAP in a dose-dependent manner,
      showing a negative correlation between logarithm of toxin dose and SEAP activity.
      However, tested toxins did not affect SEAP enzymatic activity and mRNA levels,
      but reduced the cellular release of SEAP. Moreover, in order to correct the
      monitoring of 8-keto trichothecene in crop matrix, the bioassay was proven to
      work in standard cereal extract of corn and rice. The mechanism-based monitoring
      of 8-keto trichothecenes is promising as a supplementary analysis means of the
      presence of bioactive 8-keto trichothecenes, which are potentially exposed in
      human gut epithelia.

PMID- 20682334
TI  - Phase preference for the display of activity is associated with the phase of
      extra-suprachiasmatic nucleus oscillators within and between species.
AB  - Many features of the suprachiasmatic nucleus (SCN) are the same in diurnal and
      nocturnal animals, suggesting that differences in phase preference are determined
      by mechanisms downstream from the SCN. Here, we examined this hypothesis by
      characterizing rhythmic expression of Period 1 (PER1) and Period 2 (PER2) in
      several extra-SCN areas in the brains of a diurnal murid rodent, Arvicanthis
      niloticus (grass rats). In the shell of the nucleus accumbens, dorsal striatum,
      piriform cortex, and CA1 of the hippocampus, both PER1 and PER2 were rhythmic,
      with peak expression occurring at ZT10. PER1 in the dentate gyrus also peaked at
      ZT10, but PER2 was arrhythmic in this region. In general, these patterns are 180
      degrees out of phase with those reported for nocturnal species. In a second
      study, we examined inter-individual differences in the multioscillator system of
      grass rats. Here, we housed grass rats in cages with running wheels, under which
      conditions some individuals spontaneously adopt a day active (DA) and others a
      night active (NA) phase preference. In the majority of the extra-SCN regions
      sampled, the patterns of PER1 and PER2 expression of NA grass rats resembled
      those of nocturnal species, while those of DA grass rats were similar to the ones
      seen in grass without access to running wheels. In contrast, the rhythmic
      expression of both PER proteins was identical in the SCN and ventral
      subparaventricular zone (vSPZ) of DA and NA animals. Differences in the phase of
      oscillators downstream from the SCN, and perhaps the vSPZ, appear to determine
      the phase preference of particular species, as well as that of members of a
      diurnal species that show voluntary phase reversals. The latter observation has
      important implications for the understanding of health problems associated with
      human shift work.

PMID- 20682336
TI  - Use of live imaging analysis for evaluation of cytotoxic chemicals that induce
      apoptotic cell death.
AB  - We carried out live imaging of PC12 cells expressing SCAT3, a caspase-3 cleavage
      peptide sequence linking two fluorescent proteins, ECFP and Venus, which function
      respectively as the donor and acceptor for FRET. Live imaging of SCAT3-expressing
      cells was performed from 60 to 300 min after exposure to sodium arsenite
      (NaAsO(2): 0, 1, 5, or 10 MUM) was initiated. We then measured the emission ratio
      of ECFP to Venus to monitor the activity of caspase-3 and found that the ratio
      was temporally and dose-dependently increased by NaAsO(2). The mean ECFP/Venus
      emission ratio between 200 and 300 min after exposure to NaAsO(2) at a dose of 5
      or 10 MUM, but not at 1 MUM, was significantly higher than that in the control
      group. We showed by other methods that NaAsO(2) significantly increased the
      amount and activity of mature caspase-3 and the amount of nucleosomes generated
      from DNA fragmentation, and decreased cell viability. However, methods other than
      live imaging required a longer time and higher doses of NaAsO(2) than did live
      imaging to detect significant effects. This result suggests that live imaging
      using SCAT3 is a useful method for the screening of chemical toxicities and for
      improving the efficiency of toxicity evaluation.

PMID- 20682337
TI  - Titanium ion induces necrosis and sensitivity to lipopolysaccharide in gingival
      epithelial-like cells.
AB  - Gingival epithelial-like cells (GE-1) were cultured and used to examine the
      cellular responses of gingival tissues to varying concentrations of titanium (Ti)
      ions. Titanium ions at concentrations of more than 13 ppm significantly decreased
      the viability of GE-1 cells and increased LDH release from the cells into the
      supernatant, but had no significant effect on their caspase 3 activity. These
      data suggest that a high concentration of Ti ions induced necrosis of the GE-1
      cells. Titanium ions at a concentration of 5 ppm significantly increased the
      level of CCL2 mRNA expression in GE-1 cells exposed to lipopolysaccharide derived
      from Porphyromonas gingivalis in a synergistic manner. Moreover, the mRNA
      expression levels of TLR-4 and ICAM-1 in GE-1 cells loaded with Ti ions at 9 ppm
      were significantly enhanced as compared with those in GE-1 cells without Ti
      stimulation. We suggest that Ti ions are in part responsible for monocyte
      infiltration in the oral cavity by elevating the sensitivity of gingival
      epithelial cells to microorganisms. Taken together, these data indicate that Ti
      ions may be involved in cytotoxicity and inflammation at the interfaces of dental
      implants and gingival tissue.

PMID- 20682338
TI  - Traumatic brain injury reduces soluble extracellular amyloid-beta in mice: a
      methodologically novel combined microdialysis-controlled cortical impact study.
AB  - Acute amyloid-beta peptide (Abeta) deposition has been observed in young
      traumatic brain injury (TBI) patients, leading to the hypothesis that elevated
      extracellular Abeta levels could underlie the increased risk of dementia
      following TBI. However, a recent microdialysis-based study in human brain injury
      patients found that extracellular Abeta dynamics correlate with changes in
      neurological status. Because neurological status is generally diminished
      following injury, this correlation suggested the alternative hypothesis that
      soluble extracellular Abeta levels may instead be reduced after TBI relative to
      baseline. We have developed a methodologically novel mouse model that combines
      experimental controlled cortical impact TBI with intracerebral microdialysis. In
      this model, we found that Abeta levels in microdialysates were immediately
      decreased by 25-50% in the ipsilateral hippocampus following TBI. This result was
      found in PDAPP, Tg2576, and Tg2576-ApoE2 transgenic mice producing human Abeta
      plus wild-type animals. Changes were not due to altered probe function, edema,
      changes in APP levels, or Abeta deposition. Similar decreases in Abeta were
      observed in phosphate buffered saline-soluble tissue extracts. Hippocampal
      electroencephalographic activity was also decreased up to 40% following TBI, and
      correlated with reduced microdialysate Abeta levels. These results support the
      alternative hypothesis that post-injury extracellular soluble Abeta levels are
      acutely decreased relative to baseline. Reduced neuronal activity may contribute,
      though the underlying mechanisms have not been definitively determined. Further
      work will be needed to assess the dynamics of insoluble and oligomeric Abeta
      after TBI.

PMID- 20682339
TI  - Receptors with low affinity for neurosteroids and GABA contribute to tonic
      inhibition of granule cells in epileptic animals.
AB  - Neurosteroid sensitivity of GABA(A) receptor mediated inhibition of the
      hippocampal dentate granule cells (DGCs) is reduced in animal models of temporal
      lobe epilepsy. However, the properties and subunit composition of GABA(A)
      receptors mediating tonic inhibition in DGCs of epileptic animals have not been
      described. In the DGCs of epileptic animals, allopregnanolone and L-655708
      sensitivity of holding current was diminished and delta subunit was retained in
      the endoplasmic reticulum and its surface expression was decreased the in the
      hippocampus. Ro15-4513 and lanthanum had distinct effects on holding current
      recorded from DGCs of control and epileptic animals suggesting that the
      pharmacological properties of GABA(A) receptors maintaining tonic inhibition in
      DGCs of epileptic animals were similar to those containing the alpha4betaxgamma2
      subunits. Furthermore, surface expression of the alpha4 subunit increased and a
      larger fraction of the subunit co-immunoprecipitated with the?gamma2 subunit in
      hippocampi of epileptic animals. Together, these studies revealed that functional
      alpha4betaxdelta and alpha5betaxgamma2 receptors were reduced in the hippocampi
      of epileptic animals and that novel alpha4bxgamma2 receptors contributed to the
      maintenance of tonic inhibition. The presence of alpha4betaxgamma2 receptors
      resulted in low GABA affinity and neurosteroid sensitivity of tonic currents in
      the DGCs of epileptic animals that could potentially increase seizure
      vulnerability. These receptors may represent a novel therapeutic target for
      anticonvulsant drugs without sedative actions.

PMID- 20682341
TI  - Convulsive status epilepticus duration as determinant for epileptogenesis and
      interictal discharge generation in the rat limbic system.
AB  - We analyzed with EEG-video monitoring the epileptic activity recorded during the
      latent and chronic periods in rats undergoing 30 or 120 min pilocarpine-induced
      convulsive status epilepticus (SE). Interictal discharges frequency in the
      entorhinal cortex (EC) of animals exposed to 120 min SE was significantly higher
      in the chronic than in the latent period. Following seizure appearance,
      interictal spikes diminished in duration in the CA3 of the 120 min SE group, and
      occurred at higher rates in the amygdala in all animals. Rats exposed to 120 min
      SE generated shorter seizures but presented twice as many non-convulsive seizures
      per day as the 30 min group. Finally, seizures most frequently initiated in CA3
      in the 120 min SE group but had similar onset in CA3 and EC in the 30 min group.
      These findings indicate that convulsive SE duration influences the development of
      interictal and ictal activity, and that interictal discharges undergo structure
      specific changes after seizure appearance.

PMID- 20682342
TI  - The utility of in situ detection, including RT in situ PCR, of viral nucleic acid
      and the co-localization of the cytokine response to the study of viral
      pathogenesis.
AB  - This manuscript focuses on the detection of viral nucleic acids by in situ based
      methodologies. The optimal protocol depends on the virus. We will describe
      protocols for viral RNA detection by reverse transcriptase (RT) in situ PCR. We
      will also directly compare this method to the detection of viral RNA using
      standard in situ hybridization with locked nucleic acid (LNA) probes. Most DNA
      viruses are associated with high viral copy number and, thus, can be detected by
      standard in situ hybridization. Retroviral provirus is an exception as the single
      integrated DNA is best detected by PCR in situ hybridization. We will also
      describe protocols for the co-localization of viral DNA and RNA with host
      cytokines. Our protocol typically has the protein immunohistochemistry as the
      second step, with the key features being pretreatment step, antibody
      concentration, co-labeling analyses with a computer-based system, and co-analyzes
      with serial sections.

PMID- 20682343
TI  - Structural and functional analysis of three beta-glucosidases from bacterium
      Clostridium cellulovorans, fungus Trichoderma reesei and termite Neotermes
      koshunensis.
AB  - beta-glucosidases (EC 3.2.1.21) cleave beta-glucosidic linkages in disaccharide
      or glucose-substituted molecules and play important roles in fundamental
      biological processes. beta-Glucosidases have been widely used in agricultural,
      biotechnological, industrial and medical applications. In this study, a high
      yield expression (70-250 mg/l) in Escherichia coli of the three functional beta
      glucosidase genes was obtained from the bacterium Clostridium cellulovorans
      (CcBglA), the fungus Trichoderma reesei (TrBgl2), and the termite Neotermes
      koshunensis (NkBgl) with the crystal structures of CcBglA, TrBgl2 and NkBgl,
      determined at 1.9A, 1.63A and 1.34A resolution, respectively. The overall
      structures of these enzymes are similar to those belonging to the beta-retaining
      glycosyl hydrolase family 1, which have a classical (alpha/beta)(8)-TIM barrel
      fold. Each contains a slot-like active site cleft and a more variable outer
      opening, related to its function in processing different lengths of beta-1,4
      linked glucose derivatives. The two essential glutamate residues for hydrolysis
      are spatially conserved in the active site. In both TrBgl2 and NkBgl structures,
      a Tris molecule was found to bind at the active site, explaining the slight
      inhibition of hydrolase activity observed in Tris buffer. Manganese ions at 10mM
      exerted an approximate 2-fold enzyme activity enhancement of all three beta
      glucosidases, with CcBglA catalyzing the most efficiently in hydrolysis reaction
      and tolerating Tris as well as some metal inhibition. In summary, our results for
      the structural and functional properties of these three beta-glucosidases from
      various biological sources open important avenues of exploration for further
      practical applications.

PMID- 20682344
TI  - Putting an N-terminal end to the Clostridium thermocellum xylanase Xyn10B story:
      crystal structure of the CBM22-1-GH10 modules complexed with xylohexaose.
AB  - In general, plant cell wall degrading enzymes are modular proteins containing
      catalytic domains linked to one or more non-catalytic carbohydrate-binding
      modules (CBMs). Xyn10B from Clostridium thermocellum is a typical modular enzyme
      containing an N-terminal family 22 CBM (CBM22-1), a family 10 glycoside hydrolase
      catalytic domain (GH10), a second CBM22 (CBM22-2), a dockerin sequence and a C
      terminal family 1 carbohydrate esterase (CE1) catalytic domain. The structure of
      the N-terminal bi-modular CBM22-1-GH10 component of Xyn10B has been determined
      using a SeMet derivative by SAD to 2.5A. The data was extended to 2.0A for the
      non-SeMet mutant complexed with xylohexaose. CBM22-1-GH10 is a 60kDa protein with
      an E337A mutation to render the GH10 subunit inactive. Three of the six xylose
      residues of xylohexaose are shown to be bound in the inactivated GH10 substrate
      binding cleft, with the other three sugars presumably disordered in the solvent
      channel. The protein is a dimer in the asymmetric unit with extensive surface
      contacts between the two GH10 modules and between the CBM22-1 and GH10 modules.
      Residues from helix H4 of the GH10 module provide the major contacts by fitting
      into the minor groove of the CBM22-1 module. The orientation of CBM22-1 is such
      that it would allow the substrate to be loosely bound and subsequently delivered
      to the active site in a processive manner.

PMID- 20682345
TI  - NMR characterization of foldedness for the production of E3 RING domains.
AB  - We summarize the use of NMR spectroscopy in the production and the screening of
      stability and foldedness of protein domains, and apply it to the RING domains of
      E3 ubiquitin-ligases. RING domains are involved in specific interactions with E2
      ubiquitin-conjugating enzymes and thus play an essential role in the
      ubiquitination pathway. Protein production of the Zn(2+) containing and cysteine
      rich RING domains for molecular studies frequently turns out to be problematic.
      We compared the expression and solubility of 14 E3 RING/U-box domains fused to
      the N-terminal tags of His(6), His(6)-GB1, His(6)-Trx and His(6)-GST at small
      scale and analyzed, by NMR spectroscopy, their correct folding after
      purification. The addition of GST, Trx or GB1 to the N-terminal His(6) tag
      significantly improved both the expression and solubility of target proteins as
      compared to His(6) tag alone. More importantly most of the immobilized metal
      affinity chromatography (IMAC) purified proteins were largely unfolded as judged
      by analysis of the (1)H-(15)N HSQC spectra. We demonstrate that imidazole causes
      a concentration dependent decrease in stability of RING proteins ascribed to
      metal depletion and resulting in unfolding or precipitation. In contrast, using
      glutathione affinity chromatography, the His(6)-GST fused RING and U-box domains
      were purified as correctly folded proteins with high yields. Our data clearly
      demonstrate that IMAC should be avoided and that GST-fusion affinity
      chromatography is generally applicable for expression and purification of Zn(2+)
      containing proteins.

PMID- 20682346
TI  - Molecular dynamics simulation reveals preorganization of the chloroplast FtsY
      towards complex formation induced by GTP binding.
AB  - Two GTPases in the signal recognition particle (SRP) and SRP receptor (SR)
      interact with one another to mediate the cotranslational protein targeting
      pathway. Previous studies have shown that a universally conserved SRP RNA
      facilitates an efficient SRP-SR interaction in the presence of a signal sequence
      bound to SRP. However, a remarkable exception has been found in chloroplast SRP
      (cpSRP) pathway, in which the SRP RNA is missing. Based on biochemical and
      structural analyses, it is proposed that free cpSRP receptor (cpFtsY) has already
      been preorganized into a closed state for efficient cpSRP-cpFtsY association.
      However, no direct evidence has been reported to support this postulation thus
      far. In this study, we characterized the structural dynamics of cpFtsY and its
      conformational rearrangements induced by GTP binding using molecular dynamics
      (MD) simulations. Our results showed that the GTP-binding event triggered
      substantial conformational changes in free cpFtsY, including the relative
      orientation of N-G domain and several conserved motifs that are critical in
      complex formation. These rearrangements enabled the cpFtsY to relax into a
      preorganized 'closed' state that favored the formation of a stable complex with
      cpSRP54. Interestingly, the intrinsic flexibility of alphaN1 helix facilitated
      these rearrangements. In addition, GTP binding in cpFtsY was mediated by
      conserved residues that have been shown in other SRP GTPases. These findings
      suggested that GTP-bound cpFtsY could fluctuate into conformations that are
      favorable to form the stable complex, providing explanation of why SRP-SR
      interaction bypasses the requirement of the SRP RNA at a molecular level.

PMID- 20682347
TI  - Cholesterol microcrystals and cochleate cylinders: attachment of pyolysin
      oligomers and domain 4.
AB  - Using an established organic solvent injection procedure for the preparation of
      aqueous cholesterol microcrystal suspensions, it has now been shown that a new,
      hollow, cylindrical, tightly-coiled, multi-bilayer form of cholesterol can be
      generated, termed the cochleate cylinder. Cholesterol cochleate cylinders are
      formed in larger numbers at intermediate temperatures (40-75 degrees C) but are
      not formed at 100 degrees C. The structure of the cholesterol microcrystals and
      cochleate cylinders is shown in negatively stained electron micrographs.
      Oligomerization and attachment of pyolysin to cholesterol microcrystals and
      cochleate cylinders is shown, as is the attachment of the pyolysin "cholesterol
      binding" domain 4 (D4) fragment. The bound D4 domain forms a linear array on the
      two planar surfaces and edges of the cholesterol microcrystals and a quasi
      helical array on the surface of the cochleate cylinders. Little evidence has been
      obtained to support the possibility that interaction or hetero-oligomerization
      can occur between intact pyolysin and the pyolysin D4 fragment on the surface of
      cholesterol microcrystals. Using immobilized cholesterol crystals attached to a
      carbon support film, single-sided linear labelling of the cholesterol surface
      with pyolysin D4 has been achieved, which correlates well with the images from
      the microcrystal suspensions and our earlier data using non-cytolytic
      streptolysin O mutants.

PMID- 20682340
TI  - Early changes in the hypothalamic region in prodromal Huntington disease revealed
      by MRI analysis.
AB  - Huntington disease (HD) is a fatal neurodegenerative disorder caused by an
      expanded CAG repeat. Its length can be used to estimate the time of clinical
      diagnosis, which is defined by overt motor symptoms. Non-motor symptoms begin
      before motor onset, and involve changes in hypothalamus-regulated functions such
      as sleep, emotion and metabolism. Therefore we hypothesized that hypothalamic
      changes occur already prior to the clinical diagnosis. We performed voxel-based
      morphometry and logistic regression analyses of cross-sectional MR images from
      220 HD gene carriers and 75 controls in the Predict-HD study. We show that
      changes in the hypothalamic region are detectable before clinical diagnosis and
      that its grey matter contents alone are sufficient to distinguish HD gene
      carriers from control cases. In conclusion, our study shows, for the first time,
      that alterations in grey matter contents in the hypothalamic region occur at
      least a decade before clinical diagnosis in HD using MRI.

PMID- 20682348
TI  - Atlasing location, asymmetry and inter-subject variability of white matter tracts
      in the human brain with MR diffusion tractography.
AB  - The purpose of this study is to create a white matter atlas of the human brain
      using diffusion tensor imaging (DTI) tractography and to describe the constant
      and variable features of the major pathways. DTI was acquired from 40 healthy
      right-handed adults and reconstructed tracts mapped within a common reference
      space (MNI). Group effect maps of each tract defined constant anatomical features
      while overlap maps were generated to study inter-subject variability and to
      compare DTI derived anatomy with a histological atlas. Two patients were studied
      to assess the localizing validity of the atlas. The DTI-derived maps are overall
      consistent with a previously published histological atlas. A statistically
      significant leftward asymmetry was found for the volume and number of streamlines
      of the cortico-spinal tract and the direct connections between Broca's and
      Wernicke's territories (long segment). A statistically significant rightward
      asymmetry was found for the inferior fronto-occipital fasciculus and the fronto
      parietal connections (anterior segment) of the arcuate fasciculus. Furthermore,
      males showed a left lateralization of the fronto-temporal segment of the arcuate
      fasciculus (long segment), while females had a more bilateral distribution. In
      two patients with brain lesions, DTI was acquired and tractography used to show
      that the tracts affected by the lesions were correctly identified by the atlas.
      This study suggests that DTI-derived maps can be used together with a previous
      histological atlas to establish the relationship of focal lesions with nearby
      tracts and improve clinico-anatomical correlation.

PMID- 20682349
TI  - The changes in brain metabolism in people with activated brown adipose tissue: a
      PET study.
AB  - Brown adipose tissue (BAT) is a highly specialized thermogenic tissue and has
      profound effects on body weight, energy balance, and glucose metabolism. Body
      temperature regulation depends on the integrated activities of the autonomic
      nervous system, which is centered predominantly in the hypothalamus. The purpose
      of this study was to explore the interaction of brain and the activation of BAT
      by analyzing differences in brain metabolism between patients with and without
      activated BAT. Fluorodeoxyglucose (FDG) with positron emission
      tomography/computer tomography (PET/CT) was used to determine the activation of
      BAT and brain metabolism. After reviewing FDG PET/CT scans, we retrospectively
      collected 42 patients, 21 with activated BAT and 21 matched controls without
      activated BAT. We used the method of defining regions of interest (ROI) to
      examine differences in metabolism between their hypothalami and voxel (volumetric
      pixel)-based statistical parametric mapping to analyze the whole brain. Compared
      with controls, patients with activated BAT had a significant hypermetabolic area
      in the right inferior parietal lobule (Brodmann area 40) and significant
      hypometabolic areas in the left insula (Brodmann area 13) and right cerebellum;
      however, there were no metabolic differences in the hypothalamic regions. Our
      findings illustrate the close relationship of cold temperature exposure-triggered
      hypermetabolism in the right inferior parietal lobule and activated BAT. They
      also support the hypotheses that the insula and cerebellum regulate autonomic
      functions, which are important for controlling BAT thermogenesis within the
      central pathways.

PMID- 20682350
TI  - Computing moment-to-moment BOLD activation for real-time neurofeedback.
AB  - Estimating moment-to-moment changes in blood oxygenation level dependent (BOLD)
      activation levels from functional magnetic resonance imaging (fMRI) data has
      applications for learned regulation of regional activation, brain state
      monitoring, and brain-machine interfaces. In each of these contexts, accurate
      estimation of the BOLD signal in as little time as possible is desired. This is a
      challenging problem due to the low signal-to-noise ratio of fMRI data. Previous
      methods for real-time fMRI analysis have either sacrificed the ability to compute
      moment-to-moment activation changes by averaging several acquisitions into a
      single activation estimate or have sacrificed accuracy by failing to account for
      prominent sources of noise in the fMRI signal. Here we present a new method for
      computing the amount of activation present in a single fMRI acquisition that
      separates moment-to-moment changes in the fMRI signal intensity attributable to
      neural sources from those due to noise, resulting in a feedback signal more
      reflective of neural activation. This method computes an incremental general
      linear model fit to the fMRI time series, which is used to calculate the expected
      signal intensity at each new acquisition. The difference between the measured
      intensity and the expected intensity is scaled by the variance of the estimator
      in order to transform this residual difference into a statistic. Both synthetic
      and real data were used to validate this method and compare it to the only other
      published real-time fMRI method.

PMID- 20682351
TI  - Effective connectivity anomalies in human amblyopia.
AB  - We investigate the effective connectivity in the lateral geniculate nucleus and
      visual cortex of humans with amblyopia. Six amblyopes participated in this study.
      Standard retinotopic mapping stimuli were used to define the boundaries of early
      visual cortical areas. We obtained fMRI time series from thalamic, striate and
      extrastriate cortical regions for the connectivity study. Thalamo-striate and
      striate-extrastriate networks were constructed based on known anatomical
      connections and the effective connectivities of these networks were assessed by
      means of a nonlinear system identification method. The effective connectivity of
      all networks studied was reduced when driven by the amblyopic eye, suggesting
      contrary to the current single-cell model of localized signal reduction, that a
      significant part of the amblyopic deficit is due to anomalous interactions
      between cells in disparate brain regions. The effective connectivity loss was
      unrelated to the fMRI loss but correlated with the degree of amblyopia
      (ipsilateral LGN to V1 connection), suggesting that it may be a more relevant
      measure. Feedforward and feedback connectivities were similarly affected. A
      hemispheric dependence was found for the thalamo-striate feedforward input that
      was not present for the feedback connection, suggesting that the reduced function
      of the LGN recently found in amblyopic humans may not be solely determined by the
      feedback influence from the cortex. Both ventral and dorsal connectivities were
      reduced.

PMID- 20682352
TI  - Human brain connectivity during single and paired pulse transcranial magnetic
      stimulation.
AB  - OBJECTIVE: Intracortical inhibition (SICI) and facilitation (ICF) in the human
      motor cortex can be measured using a paired pulse transcranial magnetic
      stimulation (ppTMS) protocol. Recently, a technical device has been introduced,
      which allows recording electroencephalographic (EEG) responses to TMS of a given
      scalp site. The latency, amplitude and scalp topography of such responses are
      considered a reflection of cortico-cortical connectivity and functional state.
      The aim of the present study is to better characterize the neuronal circuits
      underlying motor cortex connectivity as well as the mechanisms regulating its
      balance between inhibition and facilitation by means of EEG navigated-ppTMS
      coregistration. METHODS: Sub-threshold and supra-threshold single and ppTMS of
      the left primary motor cortex were carried out during a multi-channel EEG
      recording on 8 healthy volunteers; the between-pulse intervals used in the paired
      pulse trials were 3 (for SICI) and 11 ms (for ICF). Motor evoked potentials
      (MEPs) from the opposite hand were simultaneously recorded. RESULTS: Single and
      ppTMS induced EEG responses characterized by a sequence of negative deflections
      peaking at approximately 7, 18, 44, 100 and 280 ms alternated with positive peaks
      at approximately 13, 30, 60 and 190 ms post-TMS. Moreover, ppTMS modulated both
      EEG evoked activity and MEPs. Amplitude variability of EEG responses was
      correlated with - and therefore might partially explain - amplitude variability
      of MEPs. INTERPRETATION: EEG-ppTMS is a promising tool to better characterize the
      neuronal circuits underlying cortical effective connectivity as well as the
      mechanisms regulating the balance between inhibition and facilitation within the
      human cortices and the corticospinal pathway.

PMID- 20682353
TI  - Impact of the gyral geometry on the electric field induced by transcranial
      magnetic stimulation.
AB  - The spatial extent of the effects of transcranial magnetic stimulation (TMS) on
      neural tissue is only coarsely understood. One key problem is the realistic
      calculation of the electric field induced in the brain, which proves difficult
      due to the complex gyral folding pattern that results in an inhomogeneous
      conductivity distribution within the skull. We used the finite element method
      (FEM) together with a high-resolution volume mesh of the human head to better
      characterize the field induced in cortical gray matter (GM). The volume mesh was
      constructed from T1-weighted structural magnetic resonance images to allow for an
      anatomically accurate modeling of the gyrification pattern. Five tissue types
      were taken into account, corresponding to skin, skull, cerebrospinal fluid (CSF)
      including the ventricles as well as cortical gray and white matter. We
      characterized the effect of the current direction on the electric field
      distribution in GM. Importantly, the field strength in GM was increased by up to
      51% when the induced currents were perpendicular to the local gyrus orientation.
      This effect was mainly restricted to the gyral crowns and lips, but did not
      extend into the sulcal walls. As a result, the focality of the fields induced in
      GM was increased. This enhancement effect might in part underlie the dependency
      of stimulation thresholds on coil orientation, as commonly observed in TMS motor
      cortex studies. In contrast to the clear-cut effects of the gyrification pattern
      on the induced field strength, current directions were predominantly influenced
      by the CSF-skull boundary.

PMID- 20682354
TI  - Robustly measuring vascular reactivity differences with breath-hold: normalising
      stimulus-evoked and resting state BOLD fMRI data.
AB  - Inter-subject differences in local cerebral blood flow (CBF) and cerebral blood
      volume (CBV) contribute to differences in BOLD signal reactivity and, therefore,
      unmodelled variance in group level fMRI analyses. A simple way of elevating blood
      CO(2) concentrations to characterise subject differences in vascular reactivity
      is through breath-holds but two aspects of this measure are often neglected: (1)
      breath-holds are usually modelled as blocks even though CO(2) accumulates over
      time and (2) increases in CO(2) differ between subjects. This study demonstrates
      that the BOLD breath-hold response is best modelled by convolving the end-tidal
      CO(2) trace with a standard haemodynamic response function and including its
      temporal derivative. Inclusion of the BOLD breath-hold response as a voxel
      dependent covariate in a group level analysis increases the spatial extent of
      activation in stimulus evoked and resting state datasets. By expressing the BOLD
      breath-hold response as a percentage signal increase with respect to an absolute
      change in the partial pressure of CO(2) (expressed in mmHg), the spatial extent
      of stimulus-evoked activation is further improved. This demonstrates that
      individual end-tidal CO(2) increases to breath-hold should be accounted for to
      provide an accurate measure of vascular reactivity resulting in more
      statistically active voxels in group level analyses.

PMID- 20682355
TI  - PRP8 intein in Ajellomycetaceae family pathogens: sequence analysis, splicing
      evaluation and homing endonuclease activity.
AB  - Inteins are intervening sequences that are transcribed and translated with
      flanking host protein sequences and then self-excised by protein splicing. Bi
      functional inteins also contain a homing endonuclease responsible for their
      genetic mobility. The PRP8 intein, the most widespread among fungi, occurs in
      important pathogens such as Histoplasma capsulatum and Paracoccidioides
      brasiliensis, from the Ajellomycetaceae family. Herein, we describe the bi
      functional PRP8 intein in two other Ajellomycetacean pathogens, Blastomyces
      dermatitidis and Emmonsia parva. Sequence analysis and experimental evidence
      suggest that the homing endonuclease from PbrPRP8 is inactive. The splicing
      activity of the PRP8 intein from the B. dermatitidis, E. parva and P.
      brasiliensis species complex was demonstrated in a non-native protein context in
      Escherichia coli. Since the PRP8 intein is located in a functionally essential
      nuclear protein, it can be considered a promising therapeutic target for anti
      fungal drugs, because inhibition of intein splicing should inhibit proliferation
      of intein-containing pathogens.

PMID- 20682356
TI  - Extracellular alkalinization induces endothelium-derived nitric oxide dependent
      relaxation in rat thoracic aorta.
AB  - AIM: To investigate the mechanism through which the extracellular alkalinization
      promotes relaxation in rat thoracic aorta. METHODS: The relaxation response to
      NaOH-induced extracellular alkalinization (7.4-8.5) was measured in aortic rings
      pre-contracted with phenylephrine (Phe, 10(-6) M). The vascular reactivity
      experiments were performed in endothelium-intact and -denuded rings, in the
      presence or and absence of indomethacin (10(-5) M), NG-nitro-l-arginine methyl
      ester (L-NAME, 10(-4) M), N-(6-Aminohexyl)-5-chloro-1-naphthalenesulfonamide/HCl
      (W-7, 10(-7) M), 2,5-dimethylbenzimidazole (DMB, 2*10(-5) M) and methyl-beta
      cyclodextrin (10(-2) M). In addition, the effects of NaOH-induced extracellular
      alkalinization (pH 8.0 and 8.5) on the intracellular nitric oxide (NO)
      concentration was evaluated in isolated endothelial cells loaded with
      diaminofluorescein-FM diacetate (DAF-FM DA, 5 MUM), in the presence and absence
      of DMB (2*10(-5) M). RESULTS: The extracellular alkalinization failed to induce
      any change in vascular tone in aortic rings pre-contracted with KCl. In rings pre
      contracted with Phe, the extracellular alkalinization caused relaxation in the
      endothelium-intact rings only, and this relaxation was maintained after
      cyclooxygenase inhibition; completely abolished by the inhibition of nitric oxide
      synthase (NOS), Ca(2+)/calmodulin and Na(+)/Ca(2+) exchanger (NCX), and partially
      blunted by the caveolae disassembly. CONCLUSIONS: These results suggest that, in
      rat thoracic aorta, that extracellular alkalinization with NaOH activates the NCX
      reverse mode of endothelial cells in rat thoracic aorta, thereby the
      intracellular Ca(2+) concentration and activating the Ca(2+)/calmodulin-dependent
      NOS. In turn, NO is released promoting relaxation.

PMID- 20682357
TI  - Oxidative DNA damage contributes to the toxic activity of propylparaben in
      mammalian cells.
AB  - Propyl p-hydroxybenzoate, commonly referred to as propylparaben, is the most
      frequently used preservative to inhibit microbial growth and extend shelf life of
      a range of consumer products. The objective of this study was to provide further
      insight into the toxicological profile of this compound, because of the current
      discrepancy in the literature with regard to the safety of parabens. The Vero
      cell line, derived from the kidney of the green monkey, was selected to evaluate
      the adverse effects of propylparaben by use of a set of mechanistically relevant
      endpoints for detecting cytotoxicity and genotoxic activities. Our results
      demonstrate that exposure to the compound for 24h causes changes in cell
      proliferation rates rather than in cell viability. A significant and dose
      dependent decline in the percentage of mitotic cells was observed at the lowest
      concentration tested, mainly due to cell-cycle arrest at the G0/G1 phase.
      Immunodetection techniques revealed that induction of DNA double-strand breaks
      and oxidative damage underlies the cytostatic effect observed in treated Vero
      cells. Additional studies are in progress to extend these findings, which define
      a novel mode of action of propylparaben in cultured mammalian cells.

PMID- 20682358
TI  - Distribution of late potentials within infarct scars assessed by ultra high
      density mapping.
AB  - BACKGROUND: Late potential (LP) electrograms represent areas of slow conduction
      and are often sites critical to reentrant tachycardia circuits. The distribution
      of LPs within infarct scar is not known. OBJECTIVE: The purpose of this study was
      to delineate infarct heterogeneity using ultra high-density mapping and to
      determine the location of LPs with respect to scar architecture. METHODS:
      Detailed endocardial (n = 21) and epicardial (n = 8) ultra high-density mapping
      was performed to delineate the substrate for ventricular tachycardia (VT) in 21
      patients with ischemic cardiomyopathy. LP was defined as a low-voltage
      electrogram (< 1.5 mV) with distinct onset after the QRS. Very late potentials
      (vLPs) were classified as LPs with onset > 100 ms after the QRS. RESULTS: A mean
      of 787 +/- 391 and 810 +/- 375 points in the LV endocardium and epicardium were
      sampled. Multipolar mapping identified heterogeneous islets (HIs) with relatively
      preserved electrogram amplitudes (>= 0.51 mv) within dense scar (8.5 +/- 4.9/4.5
      +/- 2.6 HIs per endocardium/epicardium) in all patients. In maps on which
      putative VT isthmuses were identified (25/29), 57% of vLP were recorded in or
      adjacent to HI. An LP-targeted ablation strategy combined with pace mapping
      achieved acute success in all patients (complete success in 52% and partial
      success in 48%). After 15 +/- 7 months, 65% of patients remained free of VT
      episodes. CONCLUSION: Ultra high-density mapping with a multipolar catheter
      facilitates the delineation of heterogeneous scar architecture at higher
      resolution. Electrograms within and adjacent to HIs have a higher incidence of
      vLP, and these sites are frequently critical to reentry. These findings have
      important implications for substrate-based ablation strategies.

PMID- 20682359
TI  - Sudden cardiac death after myocardial infarction in patients with type 2
      diabetes.
AB  - BACKGROUND: Type 2 diabetes mellitus is a well-established risk factor for
      atherosclerosis, but its contribution to sudden cardiac death (SCD) risk after
      myocardial infarction (MI) is not well defined. OBJECTIVE: The purpose of this
      study was to compare the incidence and time-dependent risk of SCD in diabetic
      patients versus nondiabetic patients during 5-year follow-up after acute MI.
      METHODS: A total of 3,276 patients were enrolled at the time of acute MI between
      1996 and 2005. Mean age at entry was 60 +/- 11 years, and the cohort was followed
      until 2009. At entry into the study, diabetes was present in 629 (19.2%)
      patients. The primary endpoint was SCD, and the secondary endpoints were non-SCD
      and all-cause mortality. RESULTS: Among diabetic patients, the incidence of SCD
      was higher (5.9%) than in nondiabetic patients (1.7%), with a hazard ratio (HR)
      of 3.8 (95% confidence interval [CI] 2.4-5.8; P <.001) and adjusted HR of 2.3
      (95% CI 1.4-3.8; P <.01). In diabetic patients with left ventricular ejection
      fraction >35%, the incidence of SCD was nearly identical to that of nondiabetic
      patients with ventricular ejection fraction <=35% (4.1% vs 4.9%; P = .48). An
      excess in the incidence of non-SCD began to appear among diabetic patients within
      the first 6 months of follow-up (P <.001) but not in the incidence of SCD (P =
      .09). The excess in SCD among diabetic patients began to appear more than 6
      months after the index event. CONCLUSION: Patients with type 2 diabetes are at
      higher risk for SCD after MI than are nondiabetic patients. The incidence of SCD
      in post-MI type 2 diabetic patients with left ventricular ejection fraction >35%
      is equal to that of nondiabetic patients with left ventricular ejection fraction
      <35%.

PMID- 20682360
TI  - Expression of components of Wnt and Hedgehog pathways in different tissue layers
      during lung development in Xenopus laevis.
AB  - Although Wnt and Hedgehog (Hh) signaling pathways play important roles in mouse
      lung development, these have not been explored in the development of Xenopus
      lung. This may be due to the lack of specific molecular markers for different
      layers of tissue in Xenopus lung and/or insufficient knowledge on expression
      patterns of Wnt and Hh signaling components in Xenopus lung. In this study, we
      first described the early morphogenesis of Xenopus laevis lung by using
      surfactant protein C (sftpc) as a marker of lung epithelium and compared it with
      the expression patterns of several genes of Wnt and Hh pathways in Xenopus lungs.
      Our data showed that wnt7b was expressed in the entire lung epithelium from stage
      37 to stage 45, while two other Wnt signaling components, wnt5a and wif1 (wnt
      inhibitory factor 1), were expressed in the mesenchyme layer of the entire lungs
      through stages 39-41. We also found that sonic hedgehog (shh) was expressed at
      stage 41 only in the anterior, but not in the posterior part of the lungs. These
      results show the expression of wnt5a, wnt7b, wif1 and shh in different layers of
      tissue of Xenopus lungs at early developmental stages, which implies different
      roles of these genes in the early development of Xenopus lungs. Our study for the
      first time defined specific molecular markers for description of early lung
      development in Xenopus, as well as provided information about expression of
      components of Wnt and Hh pathways in early Xenopus lungs, which should be useful
      for future functional studies.

PMID- 20682361
TI  - Epithelial-to-mesenchymal transition in liver fibrosis: dead or alive?

PMID- 20682362
TI  - Covalent crosslinking of tumor antigens stimulates an antitumor immune response.
AB  - In murine renal cell carcinoma and melanoma models, vaccination with crosslinked
      tumor antigen in the absence of other adjuvants inhibited the growth of RENCA and
      B16 tumors. Vaccination with crosslinked antigens (CA9 or gp100) enhanced the
      cellular immune response as measured by ELISPOT and cytotoxicity assays.
      Crosslinking antigens enhanced delivery of antigen to bone marrow derived
      dendritic cells, which were capable of internalizing and processing the antigens.
      Dendritic cells pulsed with crosslinked antigen were effective in stimulating
      antigen-specific CD8+ T lymphocyte proliferation and interferon-gamma secretion.
      Crosslinking tumor antigens is a simple and effective strategy for enhancing
      tumor vaccines.

PMID- 20682363
TI  - Investigation of memory B cell responses to hepatitis B surface antigen in health
      care workers considered as non-responders to vaccination.
AB  - Up to 20% of health care workers are considered as non-responders to hepatitis B
      vaccination (anti-HBs<10 m UI/ml in serum). We have explored memory B cells
      differentiated in vitro into anti-HBs antibody-secreting cells (anti-HBs-SCs) by
      ELISPOT assay. Anti-HBs-SCs were detected in vaccinated responders (n = 11) and
      non-responders (n = 10) but IgG anti-HBs-SCs were significantly lower in the non
      responder group (p<0.001). Low amounts of HBs antibodies were also quantified by
      ELISA in non-responders' sera. These results indicate that a suboptimal B cell
      response exists in non-responders to HBV vaccination. This B cell response may
      mediate a protection against clinically significant breakthrough hepatitis B
      infection.

PMID- 20682365
TI  - Adenoviral vaccination combined with CD40 stimulation and CTLA-4 blockage can
      lead to complete tumor regression in a murine melanoma model.
AB  - Therapeutic vaccination with replication deficient adenovirus expressing a viral
      antigen linked to invariant chain was recently found to markedly delay the growth
      of B16.F10 melanomas expressing the same antigen; however, complete regression of
      the tumors was never observed. Here we show that the delay in tumor growth can be
      converted to complete regression and long-term survival in 30-40% of the mice by
      a booster vaccination plus combinational treatment with agonistic anti-CD40
      monoclonal antibodies (mAb) and anti-CTLA-4 mAb. Regarding the mechanism
      underlying the improved clinical effect, analysis of the tumor-specific response
      revealed a significantly prolonged tumor-specific CD8 T cell response in spleens
      of the mice receiving the combinational treatment compared with mice receiving
      either treatment individually. Matching this, CD8 T cell depletion completely
      prevented tumor control. These results indicate that even with a strong tumor
      vaccine candidate, combinatorial treatment may be required to obtain clinically
      relevant results.

PMID- 20682366
TI  - Bone loss prevention in cancer: new developments and perspectives.

PMID- 20682364
TI  - Robust IgA and IgG-producing antibody forming cells in the diffuse-NALT and lungs
      of Sendai virus-vaccinated cotton rats associate with rapid protection against
      human parainfluenza virus-type 1.
AB  - Sendai virus (SeV), a natural mouse pathogen, shows considerable promise as a
      candidate vaccine for human parainfluenza virus-type 1 (hPIV-1), and also as a
      vaccine vector for other serious pathogens of infants including respiratory
      syncytial virus (RSV). In an effort to define correlates of immunity, we examined
      the virus-specific serum antibody of cotton rats inoculated intranasally (I.N.)
      with SeV. Virus-specific antibody forming cells (AFCs) were also measured in the
      bone marrow, because these are considered responsible for durable serum antibody
      levels in other viral systems. Results showed that a single SeV inoculation was
      sufficient to induce virus-specific serum antibodies and bone marrow-resident
      AFCs that persisted for as many as 8 months post-vaccination. Given that the
      predominant SeV-specific serum antibody isotype was IgG, an isotype that traffics
      poorly to the upper respiratory tract (URT), we asked if local nasal and lung
      associated antibodies and AFCs were also present. Studies showed that: (i) SeV
      specific antibodies appeared in the URT and lower respiratory tract (LRT) within
      7 days after immunization, (ii) corresponding AFCs were present in the diffuse
      NALT (d-NALT) and lung, (iii) AFCs in the d-NALT and lung peaked at approximately
      6 weeks and persisted for the lifetime of the animal, reaching a level exceeding
      that of the bone marrow by an order of magnitude, (iv) IgA was the dominant
      isotype among AFCs in the d-NALT and lung at 4-weeks post-vaccination and
      thereafter, and (v) antibody and AFC responses associated with the prevention of
      lung infection when animals were challenged with hPIV-1 just 1 week after
      vaccination.

PMID- 20682367
TI  - The evolving role of bone-conserving therapy in patients with breast cancer.
AB  - Patients with breast cancer (BC) experience bone loss as a result of either
      cancer treatment or metastatic disease to the bone. In addition, baseline factors
      universally associated with bone loss have been identified, including history of
      fracture, menopausal status, oral corticosteroid use, osteoporosis, and smoking.
      Whereas treatment effects causing suppression of estrogen function or estrogen
      deprivation are the predominant cause of bone loss and fractures among patients
      with earlier-stage disease, metastatic lesions to the bone are the principal
      drivers of bone loss and associated skeletal complications in patients with
      advanced disease. Development of fractures and other skeletal-related events
      (SREs) is associated with adverse clinical outcome. Several studies clearly have
      demonstrated the efficacy of bisphosphonates (BPs) in the metastatic setting.
      Recently, the targeted agent denosumab also demonstrated favorable efficacy in
      preventing SREs in this setting. In addition, clinical evidence has demonstrated
      that zoledronic acid (ZOL) can prevent bone loss and may provide an anticancer
      benefit in earlier-stage breast disease, supporting the potential use of
      early/concomitant intervention with BP therapy in the adjuvant setting. Overall,
      these data warrant further consideration of the role of bisphosphonates in BC.
      Ongoing studies will further investigate the bone-protective and potential
      anticancer benefits of BPs across all stages of breast disease.

PMID- 20682368
TI  - Therapeutic options in the management of myeloma bone disease.
AB  - Advanced multiple myeloma is typically accompanied by osteolytic bone lesions
      resulting from heightened osteolytic activity of osteoclasts and decreased rates
      of osteogenesis by osteoblasts. Therefore, patients with myeloma bone disease are
      at increased risk for skeletal-related events (SREs) such as pathologic fracture,
      the need for radiotherapy or surgery to bone, spinal cord compression, and
      hypercalcemia of malignancy. Each of these can reduce patients' functional
      independence, quality of life, and survival. Radiotherapy and surgery are often
      used to palliate bone pain and to stabilize, repair, or prevent bone fractures.
      Bisphosphonates (BPs) may reduce the risk of SREs. In particular, clodronate,
      pamidronate, and zoledronic acid (ZOL) have demonstrated efficacy for delaying
      the onset of potentially life-threatening SREs. Overall, BPs have a well
      established tolerability profile. The introduction of BPs for multiple myeloma
      was practice-changing, and patients now experience far fewer serious fractures
      and hypercalcemia of malignancy. Ongoing studies will help further refine and
      optimize the timing and duration of BP therapy in patients with myeloma bone
      disease.

PMID- 20682369
TI  - The molecular basis of bisphosphonate activity: a preclinical perspective.
AB  - Bisphosphonates are widely used to preserve and improve bone health in patients
      with cancer. Emerging evidence suggests that in addition to their effects on bone
      health, bisphosphonates may have anticancer activity. Some of the activity
      associated with bisphosphonates is observed in non-osteoclast cells; therefore,
      the bioavailability of bisphosphonates is briefly discussed. Structure-function
      correlations and the molecular and cellular mechanisms that underlie
      bisphosphonate activity are also examined. In addition to a detailed discussion
      of the molecular interaction between nitrogen-containing bisphosphonates and
      farnesyl pyrophosphate synthase and the formation of cytotoxic triphosphoric acid
      1-adenosin-5'-yl ester 3-(3-methylbut-3-enyl) ester (ApppI), the effects of
      bisphosphonates on the transforming growth factor-beta (TGF)-beta pathway, the
      receptor activator of nuclear factor-kappaB (NFkappaB) ligand
      (RANKL)/osteoprotegerin (OPG) axis, and novel molecular targets are reviewed.
      Finally, a basis for the observed preclinical and clinical activity of
      bisphosphonates, including effects on apoptosis, cell proliferation, cell
      invasion, modulation of immune function, and suppression of tumor-mediated
      angiogenesis, is provided.

PMID- 20682370
TI  - Maintaining bone health in prostate cancer throughout the disease continuum.
AB  - Prostate cancer (PC) is the most prevalent malignancy in men, with 604,506 new
      cases diagnosed yearly worldwide. Maintaining bone health is important during all
      stages of PC, including patients who experience bone loss from androgen
      deprivation therapy and patients who develop bone metastases. Patients with bone
      metastases often experience severe bone pain and are at increased risk for
      potentially debilitating skeletal-related events. Bisphosphonates are a well
      established treatment option for patients with bone metastases from solid tumors
      and bone lesions from multiple myeloma. Zoledronic acid (ZOL) is the only
      bisphosphonate (BP) that has been extensively studied in patients with castration
      recurrent PC and is indicated for treating patients with bone metastases from PC
      in conjunction with standard antineoplastic therapy. This review will examine the
      breadth of evidence supporting a role for ZOL and emerging therapies in managing
      patients with PC throughout the disease continuum.

PMID- 20682371
TI  - Zoledronic acid use in patients with bone metastases from renal cell carcinoma or
      bladder cancer.
AB  - Approximately 30% of patients with renal cell carcinoma (RCC) and 40% of patients
      with bladder cancer develop bone metastases that can disrupt normal bone
      homeostasis and place patients at risk for potentially life-limiting skeletal
      related events (SREs). In the absence of bone-directed therapies, patients with
      RCC may experience up to four SREs per year. In patients with bone metastases
      from RCC or bladder cancer, zoledronic acid (ZOL) significantly reduced the risk
      of SREs compared with placebo. In addition to its bone-protective effects,
      preclinical and early clinical evidence indicates that ZOL prevents tumor
      progression. For example, retrospective subset analysis in patients with RCC
      indicated that ZOL extended time to disease progression and demonstrated a trend
      toward improved overall survival compared with placebo. Additionally, a study in
      patients with bone metastases from bladder cancer demonstrated that ZOL improved
      1-year overall survival compared with placebo. Bone metastases place a heavy
      burden on patients with RCC or bladder cancer, and early, continuous treatment
      with ZOL may provide anticancer benefits in addition to important patient quality
      of life.

PMID- 20682372
TI  - Bisphosphonates in lung cancer: more than a palliative therapy?
AB  - Bone metastases are a common complication in patients with advanced lung cancer,
      and most patients with bone metastases from lung cancer develop skeletal-related
      events (SREs). Skeletal-related events adversely impact patient quality of life
      and clinical outcome and are associated with increased costs of clinical
      management, underscoring the need for SRE prevention. Because current practice
      guidelines do not recommend pretreatment bone scans for all patients at initial
      presentation, skeletal involvement is not detected in a proportion of patients
      with early stage asymptomatic bone metastases. In addition, there are no uniform
      guidelines outlining treatment for patients with bone metastases. Although many
      bisphosphonates have not been investigated in this setting, zoledronic acid has
      proven efficacy in delaying the onset and reducing the risk of SREs in patients
      with bone metastases from lung cancer. Further, recent exploratory analyses in
      patients with bone metastases from solid tumors suggest that, in addition to
      normalizing biochemical markers of bone metabolism, zoledronic acid may improve
      survival in specific patient subsets, including those with lung cancer.
      Accordingly, several prospectively designed clinical trials assessing anticancer
      activity of zoledronic acid in the adjuvant setting are ongoing. New insights
      into the clinical relevance of bone-conserving therapy in patients with lung
      cancer are discussed.

PMID- 20682373
TI  - Potential anticancer properties of bisphosphonates.
AB  - Bisphosphonates inhibit osteoclast-mediated bone resorption, which is increased
      when cancer cells invade bone, and are used in the treatment of metastatic bone
      disease to reduce the risk of skeletal-related events. In addition, preclinical
      studies have shown that bisphosphonates, especially potent nitrogen-containing
      bisphosphonates, have direct anticancer actions. Anticancer activity includes
      induction of apoptosis, and inhibition of invasion, in addition to synergistic
      activity with chemotherapy agents, antiangiogenic properties, and modulating
      effects on the immune system. In terms of potential clinical anticancer activity,
      early data suggest that zoledronic acid may have a role to play in preventing
      metastatic disease. The definitive answer is not known as yet; however, with more
      than 20,000 patients with breast, prostate, or lung cancer currently
      participating in adjuvant bisphosphonate randomized trials, results should be
      available in the next few years. This will establish whether bisphosphonates
      given early in the course of cancer will be able to prevent formation of
      metastases, in or out of the bone environment. This review will focus on emerging
      evidence of the anticancer activities of bisphosphonates and possible underlying
      mechanisms of action.

PMID- 20682375
TI  - Defining authorship for group studies.

PMID- 20682374
TI  - Safety considerations for use of bone-targeted agents in patients with cancer.
AB  - Bisphosphonates were the first bone-directed therapies used to treat skeletal
      complications resulting from malignant bone disease. Reducing the incidence of
      skeletal complications has significantly improved patient quality of life.
      Intravenous bisphosphonates also have been evaluated as an adjunct treatment to
      minimize bone loss from cancer therapy. In these settings, there is a suggested
      improvement in cancer-associated outcomes, in addition to their bone-protective
      benefits. Denosumab is a fully human antibody to the receptor activator of
      nuclear factor-kappaB ligand. Recently reported data suggest that denosumab is
      efficacious in decreasing skeletal-related events, but the long-term safety of
      denosumab remains to be determined. The available data for the approved
      intravenous bisphosphonates, including zoledronic acid, as well as for other
      investigational bone-directed therapies is reviewed, with a focus on the
      incidence and management of treatment-associated side effects.

PMID- 20682376
TI  - Prevalence of refractive error.

PMID- 20682377
TI  - Prevalence of refractive error.

PMID- 20682379
TI  - Open angle glaucoma and stroke.

PMID- 20682380
TI  - Triamcinolone crystal size.

PMID- 20682381
TI  - Subretinal fluid resorption.

PMID- 20682382
TI  - Pseudomonas endophthalmitis.

PMID- 20682383
TI  - Metamorphosia and optical coherence tomography.

PMID- 20682386
TI  - Acute retinal necrosis.

PMID- 20682388
TI  - Amblyopia and photoscreening.

PMID- 20682390
TI  - Molecular characterization of alternative SET-NUP214 fusion transcripts in a case
      of acute undifferentiated leukemia.
AB  - Cryptic deletions are occasionally reported in hematologic malignancies. The SET
      NUP214 fusion gene has been rarely reported in acute myeloid leukemia, acute
      undifferentiated leukemia, and recurrently in T-cell acute lymphoblastic
      leukemia. The fusion product is generated by a submicroscopic deletion in the
      vicinity of 9q34. Herein we present a novel case of acute undifferentiated
      leukemia with SET-NUP214 rearrangement due to the cryptic deletion of the 9q34
      region producing two different types of fusion transcripts by alternative
      splicing and molecular characterization of the fusion transcripts by fluorescence
      in situ hybridization, reverse transcriptase-polymerase chain reaction, and array
      comparative genomic hybridization analyses.

PMID- 20682391
TI  - Cytogenetic and molecular characterization of double inversion 3 associated with
      a cryptic BCR-ABL1 rearrangement and additional genetic changes.
AB  - Rearrangements of chromosome 3 involving bands 3q21 and 3q26 have been reported
      in about 2% of patients with acute myeloid leukemia, and rarely in
      myelodysplastic syndrome or chronic myelogenous leukemia (CML). To date, only six
      cases of inversion of both homologues have been reported. Loss of normal
      chromosome 3 and duplication of the inverted chromosome have been proposed as the
      most likely mechanism, but have not been shown experimentally. We present a 36
      year-old male with an initial diagnosis of CML and resistance to imatinib
      mesylate. Chromosome analysis showed an inversion within the long arm of both
      homologues of chromosome 3 and an interstitial deletion within the long arm of
      one chromosome 7. The rearrangement of EVI1 locus on both homologues of
      chromosome 3 was confirmed by fluorescence in situ hybridization (FISH).
      Additional FISH studies showed a cryptic insertion of ABL1 into the BCR region,
      and subsequent duplication of the derivative chromosome 22. The single-nucleotide
      polymorphism array showed copy-neutral loss of heterozygosity on chromosomes 3
      and 22, suggesting that a somatic repair mechanism is involved in the evolution
      of these genetic alterations. This case illustrates the complexity of genetic
      aberrations in neoplastic cells, and the value of array technology, used in
      concert with conventional cytogenetic methods, for a better understanding of the
      pathogenesis.

PMID- 20682392
TI  - Genomic instability in patients with Barrett's esophagus.
AB  - Our study aimed to determine, by counting sister chromatid exchange (SCE) and
      micronucleus (MN) frequencies, whether genetic impairment and DNA damage have an
      effect on the pathogenesis of Barrett's esophagus (BE). This study was conducted
      between June 2007 and November 2008 in the Erzurum Training and Research
      Hospital. We analyzed SCE and MN frequencies in 30 patients with BE, and in 30
      control cases. SCE was significantly increased in BE patients compared with
      controls (6.89 +/- 1.04 vs. 5.01+/- 0.88, P < 0.001). Similarly, MN was
      significantly increased in BE patients compared with controls (3.48 +/- 1.08 vs.
      1.83 +/- 0.64, P < 0.001). Our data indicate that the increased SCE and MN rates
      in lymphocytes of patients with BE may reflect genomic instability or deficiency
      of DNA repair capacity.

PMID- 20682393
TI  - Number of somatic mutations in the mitochondrial D-loop region indicates poor
      prognosis in breast cancer, independent of TP53 mutation.
AB  - The objective of this study was to investigate whether somatic mutations in the
      mitochondrial DNA (mtDNA) D-loop region correlate with known prognostic factors,
      namely, age, tumor size, lymph node status, metastasis, tumor-node-metastasis
      stage, lymphovascular invasion, and status of the progesterone receptor, estrogen
      receptor, ERBB2 (alias HER2/neu), and TP53 proteins (as determined by
      immunohistochemistry) and to investigate their relationship, if any, to TP53
      mutations in human breast cancer. Thirty breast tumors without BRCA mutation,
      along with adjacent nontumorous tissues, were genotyped for the mtDNA D-loop
      region and for the promoter as well as the coding region of the TP53 gene.
      Clinicopathological parameters were recorded and assessed. In all, 17 somatic
      mtDNA D-loop mutations were identified, in 13 of 30 tumor samples (43%); two
      mutations were novel: 544C>T and 16510A>C. Four TP53 mutations were found in six
      tumor samples (20%), and two (c.437G>A and c.706T>C) were novel. Only
      progesterone receptor status correlated with the number of somatic mtDNA D-loop
      mutations (likelihood chi-square test; P < 0.05). Somatic mutations in the mtDNA
      D-loop and in TP53 were independent of each other (Fisher's exact test; P >
      0.05). These results suggest that the number of somatic mtDNA D-loop mutations
      may be an indicator of poor prognosis through a mechanism independent of TP53.

PMID- 20682394
TI  - MUC1 oncogene amplification correlates with protein overexpression in invasive
      breast carcinoma cells.
AB  - The MUC1 gene is aberrantly overexpressed in approximately 90% of human breast
      cancers. Several studies have shown that MUC1 overexpression is due to
      transcriptional regulatory events. However, the importance of gene amplification
      as a mechanism leading to the increase of MUC1 expression in breast cancer has
      been poorly characterized. The aim of this study was to evaluate the role of MUC1
      gene amplification and protein expression in human breast cancer development. By
      means of real-time quantitative polymerase chain reaction and immunohistochemical
      methods, 83 breast tissue samples were analyzed for MUC1 gene amplification and
      protein expression. This analysis showed MUC1 genomic amplification and a
      positive association with the histopathological group in 12% (1 out of 8) of
      benign lesions and 38% (23 out of 60) of primary invasive breast carcinoma
      samples (P = 0.004). Array-comparative genomic hybridization meta-analysis of 886
      primary invasive breast carcinomas obtained from 22 studies showed MUC1 genomic
      gain in 43.7% (387 out of 886) of the samples. Moreover, we identified a highly
      statistical significant association between MUC1 gene amplification and MUC1
      protein expression assessed by immunohistochemistry and Western blot test (P <
      0.0001). In conclusion, this study demonstrated that MUC1 copy number increases
      from normal breast tissue to primary invasive breast carcinomas in correlation
      with MUC1 protein expression.

PMID- 20682395
TI  - Emergence of two unrelated clones in acute myeloid leukemia with MLL-SEPT9 fusion
      transcript.
AB  - We report a case of acute myeloid leukemia (AML) with two unrelated clones, one
      of which was t(11;17)(q23;q25) carrying MLL-SEPT9 fusion transcripts. The patient
      was a 71-year-old man who was diagnosed with AML M0 and received multiple
      chemotherapy regimens, including DNA topoisomerase II inhibitors. Although the
      karyotype of bone marrow cells at the initial diagnosis was normal, two unrelated
      chromosomal aberrations concurrently appeared during the course of the disease,
      suggestive of t(11;17)(q23;q25) and add(1)(p36.1),del(6)(q?) by G-banding.
      Spectral karyotyping analysis identified a reciprocal translocation between
      chromosomes 11 and 17, and a translocation of the q arm of chromosome 6 to
      chromosome 1. Dual-color fluorescence in situ hybridization analysis that used
      probes specific for MLL in combination with tel 1p and tel 1q revealed a
      translocation of 1p-->pter to chromosome 6 and a translocation of 11q23-->qter to
      chromosome 17. Reverse transcriptase-polymerase chain reaction and sequencing
      analyses demonstrated MLL-SEPT9 fusion transcripts with the breakpoint of MLL
      exon 8/SEPT9 exon 2 and MLL exon 9/SEPT9 exon 2. Thus, the karyotype was defined
      as 46,XY,t(11;17)(q23;q25)/46,XY,t(1;6)(p36.3;q23). Our case represents an
      additional MLL-SEPT9-positive AML that was considered to be related to therapy.

PMID- 20682396
TI  - ider(17)(q10)t(15;17) associated with relapse and poor prognosis in a pediatric
      patient with acute promyelocytic leukemia.
AB  - Although acute promyelocytic leukemia (APL) has been regarded as a serious
      medical emergency associated with disseminated intravascular coagulopathy or
      subsequent mortality, it is now considered a curable leukemia that is
      particularly sensitive to treatment with all-trans retinoic acid combined with
      chemotherapy. However, it is not clear whether additional chromosomal
      abnormalities in APL patients directly influence the prognosis or treatment
      response. ider(17)(q10)t(15;17)(q22;q21) has mostly been reported in adult APL
      patients, and only three cases of pediatric APL associated with
      ider(17)(q10)t(15;17) showing poor prognosis have been described in the
      literature. Here, we report the close follow-up (clinical and laboratory) data of
      a pediatric APL case associated with ider(17)(q10)t(15;17). This patient had APL
      relapse from the same clone 15 months after morphological remission. Furthermore,
      despite subsequent chemotherapy, the patient died 16 months after the initial APL
      diagnosis. Although based on a limited amount of data (four pediatric APL cases),
      such results in pediatric APL patients may provide important insight into the
      relationship between ider(17)(q10)t(15;17) and poor prognosis. However, further
      well-designed case-control studies are necessary to determine the treatment
      response and prognosis in pediatric or adult APL patients with
      ider(17)(q10)t(15;17).

PMID- 20682397
TI  - Therapy-related, mixed phenotype acute leukemia with t(1;21)(p36;q22) and RUNX1
      rearrangement.
AB  - We describe here a new case of therapy-related acute leukemia with
      t(1;21)(p36;q22). A 25-year-old man was admitted because of anemia and
      thrombocytopenia. Four years before, he had received combination chemotherapy
      including etoposide for seminoma. Bone marrow was hypercellular, with 49%
      myeloperoxidase (MPO) staining-negative blasts. Chromosome analysis showed
      46,XY,t(1;21)(p36.3;q22)[11]/49,sl,+8,+16,+20[9]. Fluorescence in situ
      hybridization demonstrated that RUNX1 signals at 21q22 were split onto the
      der(1)t(1;21) and der(21)t(1;21). Immunophenotypic analyses revealed that blasts
      were positive for CD19, CD79a, and cytCD22, as well as MPO, CD13, and CD33,
      fulfilling the diagnostic criteria of mixed phenotype acute leukemia, B/myeloid.
      The patient died of disease progression after 10 months. Thus, acute leukemia
      with t(1;21) and RUNX1 rearrangement could be associated with B/myeloid mixed
      phenotype as well as previous topoisomerase II inhibitor therapy and poor
      prognoses.

PMID- 20682398
TI  - Gene methylation of SFRP2, P16, DAPK1, HIC1, and MGMT and KRAS mutations in
      sporadic colorectal cancer.
AB  - The aim of this study was to investigate the methylation of the SFRP2, P16,
      DAPK1, HIC1, and MGMT genes, as well as the mutation of amino acid codons 12 and
      13 of the KRAS gene in normal and tumor tissue DNA of patients diagnosed with
      sporadic colorectal cancer (SCRC). The methylation of gene regions and the KRAS
      mutations of normal (N) and tumor tissue (T) DNA obtained from 17 patients
      diagnosed with SCRC and 20 healthy controls were investigated using the
      polymerase chain reaction and reverse-hybridization methods. There was an Asp
      mutation in four patients, an Asp and Ser mutations in one patient in codon 12 of
      the KRAS gene, and an Asp mutation in codon 13 in eight patients. Overall
      promoter methylation (OPM) in the SFRP2 gene was observed in one N and four T,
      whereas partial promoter methylation (PPM) was observed in two N and five T. OPM
      in the P16 gene was present in one T. In the DAPK1 gene, OPM existed in seven T
      and five N, while PPM was present in two N. In the HIC1 gene, OPM was
      demonstrated in three T, while PPM was noted in two N; however, no methylation
      existed in N. In the MGMT gene, OPM occurred in five T and two N, and PPM was
      present in one T. KRAS mutations in Turkish patients with SCRC are similar to
      those of other population groups. Methylations in the genes, which underwent
      methylation analysis, were higher in T in comparison with N, and it has been
      suggested that significant results would be obtained by making a study with a
      larger population.

PMID- 20682399
TI  - Chronic myeloid leukemia with e19a2 atypical transcript: early imatinib
      resistance and complete response to dasatinib.

PMID- 20682400
TI  - Chronic myeloid leukemia with a novel four-way t(6;13;9;22)(p21;q32;q34;q11.2)
      successfully treated with imatinib mesylate.

PMID- 20682401
TI  - Health care reform: what does it mean for older adults?

PMID- 20682402
TI  - Formal caregiver burden in dementia: impact of behavioral and psychological
      symptoms of dementia and activities of daily living.
AB  - The purpose of this study was to identify the impact of the behavioral,
      psychological, and functional symptoms of dementia on the burden of formal
      caregivers. A cross-sectional study was conducted among formal caregivers caring
      for residents with dementia in Japan. The Zarit Caregiver Burden Interview (ZBI)
      personal strain items, the Personal Self-Maintenance Scale (PSMS), and the
      Troublesome Behavior Scale (TBS) were used to assess the level of formal
      caregiver burden, activities of daily living (ADL), and behavioral and
      psychological symptoms of dementia (BPSD), respectively. The data from 445
      respondents were analyzed using multiple linear regression analyses to predict
      the burden on formal caregivers. Disruptive behaviors, such as aggression,
      screaming, and a low ADL levels among residents with dementia were significantly
      correlated with higher formal caregiver burden. The results of this study support
      a positive relationship between BPSD, low ADL levels, and formal caregiver burden
      in caring for residents with dementia. These results illustrate the various
      characteristics of the burdens on staff members compared with those faced by
      individuals who provide informal care.

PMID- 20682403
TI  - Exploration of informal caregiving following hip fracture.
AB  - Hip fracture, a significant health issue for older adults, is an acute event in
      which older adults can recover their prefracture functional abilities. The
      recovery phase is often difficult for older adults, and the role of informal
      caregivers is particularly important. The aim of this qualitative study was to
      explore informal caregivers' experiences with providing care to older adults over
      the first 6-month trajectory of hip fracture recovery and their support needs.
      Participants (N = 10) were interviewed twice at 0-2 and 5-6 months. Analyses of
      the verbatim transcripts revealed multiple shared themes. Some themes were
      consistent across phases, such as hip fracture as a turning point toward a
      frailer state, feeling tired, frustration with communication issues in health
      care delivery, and lack of information about caregiving-related activities.
      Certain themes were phase-specific. For instance, in the early phase, management
      of hospital bills and transitions between care settings were especially
      burdensome. The caregiving situation, however, was viewed as an opportunity to
      spend more time with their loved ones. Findings from this study revealed unmet
      support needs expressed by caregivers of older adult hip fracture patients.
      Ongoing research and clinical interventions are needed to establish effective
      methods to empower these caregivers.

PMID- 20682404
TI  - Sleep in hospitalized elders: a pilot study.
AB  - Hospitalized elders frequently experience disturbed sleep related to
      environmental factors. To determine relationships between sleep and environmental
      noise and light, a descriptive exploratory study was conducted with 48
      hospitalized older adults. Participants aged 70 years or older were monitored for
      sleep via wrist actigraphy, and noise and light levels were measured the first
      night of hospitalization. Sleep time was brief (mean, 3.75 hours) and fragmented
      (mean, 13 awakenings per night). The sleep environment was noisy with a median
      sound level of 49.65 dB(A). There was an average of 3 periods of elevated light
      levels (mean, 64 lux) lasting an average of 1.75 hours each night. No significant
      correlation was found among sleep and age, light, and sound. Recommendations
      include light and sound reduction measures and dedicated "do not disturb" times
      to allow for a full 90-minute sleep cycle.

PMID- 20682405
TI  - Dissemination and benefits of a replicable Tai Chi and Qigong program for older
      adults.
AB  - Tai Chi and Qigong (TCQG) show promise for improving many health outcomes and are
      recommended for dissemination to older adults. A simplified, easy-to-replicate
      version of TCQG, "Tai Chi Easy," was tested using a train-the-trainer method to
      demonstrate feasibility of dissemination to a widespread population of older
      adults through community sites and achievement of perceived outcomes. Nonexpert
      facilitators known as "practice leaders" were trained to implement Tai Chi Easy
      sessions at 18 sites across the United States. Outstanding facilitator (100%) and
      participant (94%) adherence was achieved. With 330 completers, mean age 73 years,
      significant improvements were found for participants' perceived stress levels (P
      = .003). Sleep quality and energy/vitality were markedly improved. Eighty-nine
      percent enjoyed the program, 91% were committed to continue, and 67% stated that
      they had increased their weekly levels of physical activity. A train-the
      facilitator model for Tai Chi Easy is easily disseminated to older adults and may
      promote a sustainable alternative exercise, yielding favorable quality of life
      benefits.

PMID- 20682406
TI  - Complementary and alternative medicines: clinical pearls for commonly used
      dietary supplements.

PMID- 20682407
TI  - Important rule affecting nurse practitioners and clinical nurse specialists
      relating to enrollment, documentation, and ordering and referring requirements.

PMID- 20682408
TI  - Medication adherence is a partnership, medication compliance is not.
AB  - Medication adherence is a complex phenomenon. As individuals assume greater
      responsibility for, and participation in, decisions about their health care,
      teaching and supporting adherence behaviors that reflect a person's unique
      lifestyle are the essence of a clinician-patient partnership-and it is a perfect
      fit with assisted living communities and nursing practice. The notion of
      compliance is an outdated concept and should be abandoned as a clinical
      practice/goal in the medical management of patient and illness. It connotes
      dependence and blame and does not move the patient forward on a pathway of better
      clinical outcomes. This article discusses the differences between compliance and
      adherence, identifies purposeful and unintentional reasons for nonadherence, and
      describes assessment tools for adherence, medication effect, and self-management
      capacity. Drawing on the scholarly work of others, we introduce a model for
      medication adherence, the ACE-ME Model: assessment, collaboration, education,
      monitoring, and evaluation. This model draws on the strengths and science of
      nursing and engages nursing participation in the continuing evolution of
      adherence strategies. For purposes of clarity in discussing these concepts, we
      use the word patient in this article rather than the word resident-that is, the
      older adult living in an assisted living community.

PMID- 20682409
TI  - Geriatric syndromes in practice: delirium is not the only thing.

PMID- 20682410
TI  - Forensic odontology special issue--September 2010.

PMID- 20682411
TI  - Understanding heterogeneous diseases in mtDNA maintenance.

PMID- 20682412
TI  - Infection, ischemia, and amputation. Preface.

PMID- 20682413
TI  - Decision making in the dysvascular lower extremity.
AB  - Given the aging population, the number of patients at risk for peripheral
      arterial disease and critical limb ischemia will increase in the upcoming decade.
      Using a focused history and physical examination, along with a combination of
      noninvasive physiologic testing and noninvasive and invasive imaging modalities,
      one can accurately assess the location and physiologic effect of peripheral
      arterial disease. This assessment then allows the selection of the most
      appropriate treatment option for each patient. Treatment options may include
      exercise and risk-factor modification, amputation, and endovascular or surgical
      revascularization or a combination of both.

PMID- 20682414
TI  - Bone and wound healing in the diabetic patient.
AB  - Impaired soft tissue regeneration and delayed osseous healing are known
      complications associated with diabetes mellitus with regard to orthopedic
      surgery, making the management and treatment of diabetic patients undergoing foot
      and ankle surgery more complex and difficult. At the moment several options are
      available to address the known issues that complicate the clinical outcomes in
      these high-risk patients. Using a multifaceted approach, with close attention to
      intraoperative and perioperative considerations including modification of
      surgical technique to supplement fixation, local application of orthobiologics,
      tight glycemic control, administration of supplementary oxygen, and biophysical
      stimulation via low-intensity pulsed ultrasound and electrical bone stimulation,
      the impediments associated with diabetic healing can potentially be overcome, to
      yield improved clinical results for diabetic patients after acute or elective
      foot and ankle surgery.

PMID- 20682415
TI  - Angiosomes and wound care in the diabetic foot.
AB  - Successful foot and ankle reconstructions require a detailed knowledge of
      vascular anatomy. This knowledge becomes all the more important in diabetic
      patients because of healing complications and high incidence of peripheral
      vascular disease; it allows foot and ankle surgeons to design safe exposures and
      vascular surgeons to choose effective revascularization strategies. The angiosome
      concept separates the body into distinct threedimensional blocks of tissue fed by
      source arteries. This article focuses on the surgical implications of angiosomes
      of the foot and ankle and their arterial-arterial connections.

PMID- 20682416
TI  - Surgery for diabetic foot infections.
AB  - Diabetes mellitus is a common disease in the world today and its prevalence is
      increasing. Foot and ankle complications, including infection, are the most
      common reason for hospital admission in patients with diabetes mellitus in the
      United States and are commonly encountered by the foot and ankle surgeon.
      Thorough clinical examination with appropriate use of adjunctive laboratory and
      imaging studies can allow for early diagnosis and treatment, which can improve
      patient outcomes. Mild infections can often be treated on an outpatient basis
      with oral antibiotics and local debridement, whereas more severe infections
      require hospitalization, intravenous antibiotics, and surgical debridement to
      fully eradicate the infection. Despite proper treatment, amputation is still
      common in diabetics.

PMID- 20682417
TI  - The infected calcaneus.
AB  - Infections in and around the calcaneus can be quite challenging for the patients
      and physicians involved. These infections arise because of multiple potential
      etiologies including chronic pressure, trauma, and postsurgical wound-healing
      complications. The impediments to healing can be equally as diverse depending on
      patients' comorbidities, such as smoking, diabetes, and open injury. In this
      article the authors review the anatomy of the calcaneus and surrounding soft
      tissue, patient risk factors, and various treatment options that can be used
      through a multidisciplinary approach. The common limiting factor for most of
      these patients is the delicate soft-tissue envelope, and occasionally, the lack
      thereof. The ultimate goal is an infection-free limb with durable soft-tissue
      coverage and maximal maintenance of function.

PMID- 20682418
TI  - Syme's ankle disarticulation.
AB  - The Syme's ankle disarticulation is an end-bearing amputation level that provides
      stable walking, requires minimal physical therapy gait training, and rarely
      requires hospitalization on a rehabilitation unit. This article discusses patient
      selection, surgical technique, and rehabilitation of an underused rehabilitation
      amputation level.

PMID- 20682419
TI  - Risk and prevention of reulceration after partial foot amputation.
AB  - Partial foot amputations are frequently performed to salvage significant portions
      of the lower extremity affected by limb-threatening infection. Once healed, the
      residual foot is at high risk for reulceration. Careful long-term follow-up and
      appropriate interventions can lower this risk.

PMID- 20682420
TI  - Gait abnormality following amputation in diabetic patients.
AB  - Amputations of the lower extremity may result from several etiologic factors.
      Most amputations performed in the United States result from a dysvascular limb. A
      majority of the population with vascular impairment comprises people with
      diabetes. These individuals frequently have comorbidities that may also affect
      the ultimate outcome of amputation. Loss of protective sensation, propensity
      toward infection, and visual and balance impairment all create additional issues
      with postamputation gait in the population with diabetes. Amputations about the
      foot and ankle affect gait and energy consumption. More gait disturbances tend to
      be seen as amputation level becomes more proximal; however, loss of the
      metatarsophalangeal joints has a profound effect, regardless of the proximal
      level of amputation. Soft tissue balance is key to maximizing gait, particularly
      prevention of equinus and equinovarus deformity from unopposed plantarflexors.
      Orthotic, prosthetic, and shoe modifications can help minimize gait
      abnormalities; however alterations of ground reaction force and center of
      pressure may still remain.

PMID- 20682421
TI  - Shoes, orthoses, and prostheses for partial foot amputation and diabetic foot
      infection.
AB  - Amputations in patients with diabetes, while often preventable, are unfortunately
      a far too common outcome. The roles of the certified or licensed pedorthist,
      certified orthotist, and the certified prosthetist should not be undervalued in
      the prevention of diabetic foot complications (eg, amputations, revisions, and
      foot infections secondary to skin ulcerations) and in returning the patient a
      normal, active, and productive lifestyle in the event of an amputation. This
      article highlights the roles these specialists play in treating patients with
      partial foot amputation.

PMID- 20682422
TI  - Preface: advances and updates in internal medicine.

PMID- 20682423
TI  - Diagnostic techniques and treatments for internal disorders of Koi (Cyprinus
      carpio).
AB  - The most common problems that occur in koi involve external pathogens and
      environmental conditions. Techniques for external fish examination and water
      quality analysis have been well described in the veterinary literature. However,
      there are also some internal disorders of koi, such as gas bladder abnormalities
      affecting the fish's buoyancy, neoplasia, egg binding (roe retention), and spinal
      disorders that can be diagnosed with common veterinary medical procedures.
      Diagnostic techniques along with available treatments for these disorders are
      presented in this article.

PMID- 20682424
TI  - Updates and practical approaches to reproductive disorders in reptiles.
AB  - Reproductive biology and disorders are important facets of captive reptile
      management and are relatively common reasons for reptiles to present to the
      veterinarian. Although the factors and conditions for normal reproduction differ
      between species depending on their natural histories, the general principles and
      common approaches to disorders are presented in this article. Frequently seen
      disorders addressed in this review include infertility or lack of conception,
      follicular stasis, dystocia, and reproductive organ prolapse. This article is
      divided into sections based on the taxonomic groups, although many of the
      predisposing factors for and the approaches to these conditions are similar for
      all the groups.

PMID- 20682425
TI  - A fresh look at metabolic bone diseases in reptiles and amphibians.
AB  - Metabolic bone diseases (MBDs) are a common presenting complaint in reptiles and
      amphibians to veterinarians; however, understanding of the causes and diagnostic
      and treatment options is often extrapolated from human or other mammalian
      medicine models. Although the roles of UV-B, calcium, phosphorus, and
      cholecalciferol are better understood in some MBDs, there remain many X factors
      that are not. Likewise, quantitative diagnosis of MBDs has been difficult not
      only in terms of staging a disease but also regarding whether or not a condition
      is present. Treatment options also present challenges in corrective husbandry and
      diet modifications, medication/modality selection, and dosing/regimen parameters.

PMID- 20682426
TI  - Avian renal system: clinical implications.
AB  - The avian renal system differs anatomically and physiologically from the
      mammalian renal system. However, it is affected by similar disease categories
      such as infectious, nutritional, degenerative, congenital, metabolic, and
      neoplastic conditions. The diagnosis of renal disease in birds can be challenging
      and, in many cases, diagnosis is made on postmortem examination. Successful
      treatment of avian renal disease requires early recognition of clinical signs and
      correct interpretation of diagnostic tools.

PMID- 20682427
TI  - Advanced diagnostic approaches and current management of avian hepatic disorders.
AB  - Although the diagnosis of liver disease is common in avian patients, it is often
      based on subjective or inadequate evidence. Diagnosis of the inciting cause,
      determination of the severity of the tissue damage, and assessment of the
      remaining hepatobiliary function can be clinically challenging. A basic review of
      avian normal hepatic anatomy and function is included in this article as a
      foundation for further discussion of testing methods used to diagnose liver
      disease. Interpretation of abnormalities noted on the physical examination,
      clinical pathologic testing, and imaging studies in a patient with hepatic
      dysfunction are presented, and the methods of obtaining a hepatic biopsy are
      discussed. Therapies targeted at treating secondary complications of hepatic
      dysfunction and at supporting hepatocellular function and regeneration are also
      reviewed.

PMID- 20682428
TI  - Management of common psittacine reproductive disorders in clinical practice.
AB  - The reproductive organs play a key role in the maintenance of normal homeostasis
      in psittacine birds. For this reason, sex determination should be part of the
      baseline data collected on every avian patient. Disorders of the psittacine
      reproductive tract can have a negative effect on the function of other organ
      systems in the body. Reproductive organs may be plagued by a multitude of
      problems ranging from infection and neoplasia to inflammation and idiopathic
      issues that affect fertility. Detection of reproductive problems may require the
      use of a variety of modalities. The ability to treat these problems often depends
      on the presenting complaint as well as the clinical condition of the avian
      patient. Different reproductive disorders of male and female psittacine birds,
      with their detection and treatment are discussed in this article.

PMID- 20682429
TI  - Advanced diagnostic approaches and current medical management of insulinomas and
      adrenocortical disease in ferrets (Mustela putorius furo).
AB  - Endocrine neoplasia is the most common tumor type in domestic ferrets, especially
      in middle-aged to older ferrets. Islet cell tumors and adrenocortical tumors
      constitute the major types of endocrine neoplasms. Insulinoma is a tumor that
      produces and releases excessive amounts of insulin. Evaluation of fasted blood
      glucose levels provides a quick diagnostic assessment for the detection of
      insulinomas. Use of glucocorticoids, diazoxide, and diet modification are some of
      the medical treatment options for insulinomas. Adrenocortical neoplasia in
      ferrets usually overproduces one or more sex hormones. Sex hormones which can
      result in progressive alopecia, vulvar swelling in females, and prostagomegaly in
      males. Abdominal ultrasonography and sex hormone assays can be used to diagnose
      adrenocortical neoplasms. Drugs such as leuprolide acetate, deslorelin acetate,
      and the hormone melatonin can be used to treat adrenocortical neoplasms in
      ferrets when surgery is not an option.

PMID- 20682430
TI  - Advanced diagnostic approaches and current management of internal disorders of
      select species (rodents, sugar gliders, hedgehogs).
AB  - African pygmy and European hedgehogs, sugar gliders, and rodents such as rats,
      mice, gerbils, hamsters, guinea pigs, and chinchillas are becoming increasingly
      popular as pets in the United States, and more practitioners are being asked to
      examine, diagnose, and treat these animals for a bevy of disorders and diseases.
      Many procedures and techniques used in traditional small and large animal
      medicine are used for these species, with minor adaptations or considerations.
      This article examines available diagnostic tools and treatment methodologies for
      use in hedgehogs, sugar gliders, and selected rodents.

PMID- 20682431
TI  - Advanced diagnostic approaches and current management of proventricular
      dilatation disease.
AB  - Proventricular dilatation disease (PDD) is a fatal inflammatory disease that
      affects mainly, but not exclusively, psittacine birds (Order: Psittaciformes).
      PDD has long been suspected to be a viral disease, but its causative agent, a
      novel Bornavirus, was only identified in 2008.

PMID- 20682432
TI  - The isolation, pathogenesis, diagnosis, transmission, and control of avian
      bornavirus and proventricular dilatation disease.
AB  - Proventricular dilatation disease (PDD) is a common infectious neurologic disease
      of birds comprising a dilatation of the proventriculus by ingested food as a
      result of defects in intestinal motility, which affects more than 50 species of
      psittacines, and is also known as Macaw wasting disease, neuropathic
      ganglioneuritis, or lymphoplasmacytic ganglioneuritis. Definitive diagnosis of
      PDD has been problematic due to the inconsistent distribution of lesions. Since
      its discovery, avian bornavirus (ABV) has been successfully cultured from the
      brains of psittacines diagnosed with PDD, providing a source of antigen for
      serologic assays and nucleic acid for molecular assays. This article provides
      evidence that ABV is the etiologic agent of PDD. Recent findings on the
      transmission, epidemiology, pathogenesis, diagnosis, and control of ABV infection
      and PDD are also reviewed.

PMID- 20682433
TI  - Advanced diagnostic approaches and current management of thyroid pathologies in
      Guinea pigs.
AB  - The authors have encountered multiple clinical cases of clinical hyperthyroidism
      in the guinea pig, which responded positively to clinical treatment. Hyperactive
      thyroids in the guinea pig appear to exist causing typical clinical signs. An
      early accurate diagnosis of this pathologic state is important in the clinical
      setting. One of the authors has encountered a few clinical cases of
      hypothyroidism in guinea pigs. Hypothyroidism appears to be a rare condition and
      has been described anecdotally in the German literature. Because of the rarity of
      hypothyroidism, the text focuses mainly on the guinea pig as a hyperthyroid case.
      A short description of the clinical presentation of the hypothyroid animal is
      included at the end of the text.

PMID- 20682434
TI  - Updates and advanced therapies for gastrointestinal stasis in rabbits.
AB  - Gastrointestinal stasis is currently a vaguely defined term for decreased
      gastrointestinal motility. The term gastric stasis syndrome was previously
      proposed, but falls short of an accurate description, as in many cases portions
      of the gastrointestinal tract other than the stomach are affected. The term
      rabbit gastrointestinal syndrome (RGIS) defines a complex of clinical signs,
      symptoms, and concurrent pathologic conditions affecting the digestive apparatus
      of the rabbit. When ill rabbits present for examination it is important to
      determine if RGIS is present and if so, begin treatment and a diagnostic workup
      to determine underlying contributing factors. Identification of underlying cause
      is often difficult; many rabbits present with evidence of RGIS whereby attempts
      to identify an underlying cause are unfruitful. In many cases, these rabbits
      respond positively to supportive therapy including fluids, hand feeding, and
      motility-enhancing drugs.

PMID- 20682435
TI  - Ferret coronavirus-associated diseases.
AB  - A novel coronavirus of ferrets was first described in 1993. This coronavirus
      caused an enteric disease called epizootic catarrhal enteritis (ECE). Recently, a
      ferret systemic coronavirus (FRSCV)-associated disease was discovered. This new
      systemic disease resembles the dry form of feline infectious peritonitis (FIP)
      and has been reported in the United States and Europe. This article addresses the
      clinical signs, pathology, pathogenesis, diagnosis, treatment, and prevention of
      this ferret FIP-like disease.

PMID- 20682436
TI  - Disseminated idiopathic myofasciitis in ferrets.
AB  - First described in 2003, disseminated idiopathic myofasciitis (DIM) has emerged
      as a new disease in young, domestic ferrets. DIM is a severe inflammatory
      condition that affects primarily muscles and surrounding connective tissues. The
      disease is characterized by rapid onset of clinical signs, high fever,
      neutrophilic leukocytosis, and general lack of response to therapeutic
      intervention. Until recently DIM was considered fatal, but a few surviving
      ferrets indicate there may be an effective treatment protocol. DIM is suspected
      to be an immune-mediated disease, but the etiopathogenesis is not known. This
      article reviews clinical and pathologic findings in DIM patients, covers
      recommended diagnostic procedures and clinical management of ferrets with DIM,
      and discusses potential etiologies for this newly recognized disease in ferrets.

PMID- 20682437
TI  - Dying alone: a tale of rho.
AB  - In this issue of Cell Stem Cell, Chen et al. (2010) and Ohgushi et al. (2010)
      report that Rho-mediated actomyosin contractility underlies the proclivity of
      human embryonic stem cells to undergo apoptosis upon dissociation or during low
      density propagation, a property that challenges their in vitro isolation and
      manipulation.

PMID- 20682438
TI  - Recreating pluripotency?
AB  - Two Matters Arising articles in this issue challenge the conclusions of a
      previous Cell Stem Cell paper that found extensive transcriptional differences
      between hESCs and hiPSCs. The original authors provide a response and set in
      motion a discussion in the field about appropriate methods for microarray data
      analysis.

PMID- 20682439
TI  - Getting to the heart of the matter: direct reprogramming to cardiomyocytes.
AB  - Since MyoD was used to convert fibroblasts directly to skeletal muscle,
      biologists have tried to apply this strategy to generate other cell lineages. In
      their recent Cell paper, Ieda et al. (2010) use selected cardiac transcription
      factors to directly reprogram fibroblasts to cardiomyocytes without passing
      through an intervening pluripotent state.

PMID- 20682440
TI  - There's no place like home for a neural stem cell.
AB  - Neural precursor cells (NPCs) reside in the subventricular zone in association
      with blood vessels and ependymal cells. In this issue of Cell Stem Cell, Kokovay
      et al. (2010) show that SDF1 directs the association of NPCs with this niche and
      regulates their lineage progression in a stage-specific manner.

PMID- 20682441
TI  - Keeping the epidermal stem cell niche in shape.
AB  - Recently in Nature Cell Biology,Connelly et al. (2010) identified biomechanical
      sensing mechanisms that link the physical shape of the stem cell microenvironment
      to epithelial stem cell fate decisions. Ultimately, the integration of extrinsic
      and intrinsic signals controls stem cell self-renewal or differentiation.

PMID- 20682442
TI  - Differential DNA damage response in stem and progenitor cells.
AB  - The long lifespan of tissue-specific stem cells suggests that they may respond
      differently to DNA damage than downstream cells. In this issue of Cell Stem Cell,
      two groups address this hypothesis by examining DNA damage responses in
      hematopoietic stem and progenitor cells (Milyavsky et al., 2010; Mohrin et al.,
      2010).

PMID- 20682443
TI  - Graft-induced dyskinesias in Parkinson's disease: what is it all about?
AB  - The treatment of Parkinson's disease with grafts of fetal ventral mesencephalic
      tissue has shown some success, but can result in graft-induced dyskinesias
      (GIDs). Recently in Science Translational Medicine, Politis et al. (2010)
      demonstrate that GIDs may originate from serotoninergic neurons that are
      cografted in these transplants.

PMID- 20682444
TI  - Oxygen in stem cell biology: a critical component of the stem cell niche.
AB  - The defining hallmark of stem cells is their ability to self-renew and maintain
      multipotency. This capacity depends on the balance of complex signals in their
      microenvironment. Low oxygen tensions (hypoxia) maintain undifferentiated states
      of embryonic, hematopoietic, mesenchymal, and neural stem cell phenotypes and
      also influence proliferation and cell-fate commitment. Recent evidence has
      identified a broader spectrum of stem cells influenced by hypoxia that includes
      cancer stem cells and induced pluripotent stem cells. These findings have
      important implications on our understanding of development, disease, and tissue
      engineering practices and furthermore elucidate an added dimension of stem cell
      control within the niche.

PMID- 20682445
TI  - Adult SVZ lineage cells home to and leave the vascular niche via differential
      responses to SDF1/CXCR4 signaling.
AB  - Neural progenitor cells (NPCs) in the adult subventricular zone (SVZ) are
      associated with ependymal and vasculature niches, which regulate stem cell self
      renewal and differentiation. Activated Type B stem cells and their progeny, the
      transit-amplifying type C cells, which express EGFR, are most highly associated
      with vascular cells, indicating that this niche supports lineage progression.
      Here, we show that proliferative SVZ progenitor cells home to endothelial cells
      in a stromal-derived factor 1 (SDF1)- and CXC chemokine receptor 4 (CXCR4)
      dependent manner. We show that SDF1 strongly upregulates EGFR and alpha6 integrin
      in activated type B and type C cells, enhancing their activated state and their
      ability to bind laminin in the vascular niche. SDF1 increases the motility of
      type A neuroblasts, which migrate from the SVZ toward the olfactory bulb. Thus,
      differential responses to SDF1 can regulate progenitor cell occupancy of and exit
      from the adult SVZ vascular niche.

PMID- 20682446
TI  - Transient inactivation of Rb and ARF yields regenerative cells from postmitotic
      mammalian muscle.
AB  - An outstanding biological question is why tissue regeneration in mammals is
      limited, whereas urodele amphibians and teleost fish regenerate major structures,
      largely by cell cycle reentry. Upon inactivation of Rb, proliferation of
      postmitotic urodele skeletal muscle is induced, whereas in mammalian muscle this
      mechanism does not exist. We postulated that a tumor suppressor present in
      mammals but absent in regenerative vertebrates, the Ink4a product ARF
      (alternative reading frame), is a regeneration suppressor. Concomitant
      inactivation of Arf and Rb led to mammalian muscle cell cycle reentry, loss of
      differentiation properties, and upregulation of cytokinetic machinery. Single
      postmitotic myocytes were isolated by laser micro-dissection-catapulting, and
      transient suppression of Arf and Rb yielded myoblast colonies that retained the
      ability to differentiate and fuse into myofibers upon transplantation in vivo.
      These results show that differentiation of mammalian cells is reversed by
      inactivation of Arf and Rb and support the hypothesis that Arf evolved at the
      expense of regeneration.

PMID- 20682447
TI  - Mouse germ line stem cells undergo rapid and stochastic turnover.
AB  - In cycling tissues, adult stem cells may be lost and subsequently replaced to
      ensure homeostasis. To examine the frequency of stem cell replacement, we
      analyzed the population dynamics of labeled stem cells in steady-state mouse
      spermatogenesis. Our results show that spermatogenic stem cells are continuously
      replaced, on average within 2 weeks. The analysis exposes a simple and robust
      scaling behavior of clone size distributions that shows stem cell replacement to
      be stochastic, meaning that stem cells are equipotent and equally likely to be
      lost or to multiply to replace their neighbors, irrespective of their clonal
      history. The surprisingly fast rate of stem cell replacement is supported
      experimentally by 3D clone morphology and by live-imaging of spermatogonial
      migration. These results suggest that short-lived stem cells may be a common
      feature of mammalian stem cell systems and reveal a natural mechanism for
      matching the rates of cell proliferation and loss in tissue.

PMID- 20682448
TI  - Molecular pathway and cell state responsible for dissociation-induced apoptosis
      in human pluripotent stem cells.
AB  - Human embryonic stem cells (hESCs), unlike mouse ones (mESCs), are vulnerable to
      apoptosis upon dissociation. Here, we show that the apoptosis, which is of a
      nonanoikis type, is caused by ROCK-dependent hyperactivation of actomyosin and
      efficiently suppressed by the myosin inhibitor Blebbistatin. The actomyosin
      hyperactivation is triggered by the loss of E-cadherin-dependent intercellular
      contact and also observed in dissociated mouse epiblast-derived pluripotent cells
      but not in mESCs. We reveal that Abr, a unique Rho-GEF family factor containing a
      functional Rac-GAP domain, is an indispensable upstream regulator of the
      apoptosis and ROCK/myosin hyperactivation. Rho activation coupled with Rac
      inhibition is induced in hESCs upon dissociation, but not in Abr-depleted hESCs
      or mESCs. Furthermore, artificial Rho or ROCK activation with Rac inhibition
      restores the vulnerability of Abr-depleted hESCs to dissociation-induced
      apoptosis. Thus, the Abr-dependent "Rho-high/Rac-low" state plays a decisive role
      in initiating the dissociation-induced actomyosin hyperactivation and apoptosis
      in hESCs.

PMID- 20682449
TI  - Actin-myosin contractility is responsible for the reduced viability of
      dissociated human embryonic stem cells.
AB  - Human ESCs are the pluripotent precursor of the three embryonic germ layers.
      Human ESCs exhibit basal-apical polarity, junctional complexes, integrin
      dependent matrix adhesion, and E-cadherin-dependent cell-cell adhesion, all
      characteristics shared by the epiblast epithelium of the intact mammalian embryo.
      After disruption of epithelial structures, programmed cell death is commonly
      observed. If individualized human ESCs are prevented from reattaching and forming
      colonies, their viability is significantly reduced. Here, we show that actin
      myosin contraction is a critical effector of the cell death response to human ESC
      dissociation. Inhibition of myosin heavy chain ATPase, downregulation of myosin
      heavy chain, and downregulation of myosin light chain all increase survival and
      cloning efficiency of individualized human ESCs. ROCK inhibition decreases
      phosphorylation of myosin light chain, suggesting that inhibition of actin-myosin
      contraction is also the mechanism through which ROCK inhibitors increase cloning
      efficiency of human ESCs.

PMID- 20682450
TI  - Chromatin structure and gene expression programs of human embryonic and induced
      pluripotent stem cells.
AB  - Knowledge of both the global chromatin structure and the gene expression programs
      of human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs)
      should provide a robust means to assess whether the genomes of these cells have
      similar pluripotent states. Recent studies have suggested that ESCs and iPSCs
      represent different pluripotent states with substantially different gene
      expression profiles. We describe here a comparison of global chromatin structure
      and gene expression data for a panel of human ESCs and iPSCs. Genome-wide maps of
      nucleosomes with histone H3K4me3 and H3K27me3 modifications indicate that there
      is little difference between ESCs and iPSCs with respect to these marks. Gene
      expression profiles confirm that the transcriptional programs of ESCs and iPSCs
      show very few consistent differences. Although some variation in chromatin
      structure and gene expression was observed in these cell lines, these variations
      did not serve to distinguish ESCs from iPSCs.

PMID- 20682451
TI  - Lab-specific gene expression signatures in pluripotent stem cells.
AB  - Pluripotent stem cells derived from both embryonic and reprogrammed somatic cells
      have significant potential for human regenerative medicine. Despite similarities
      in developmental potential, however, several groups have found fundamental
      differences between embryonic stem cell (ESC) and induced-pluripotent stem cell
      (iPSC) lines that may have important implications for iPSC-based medical
      therapies. Using an unsupervised clustering algorithm, we further studied the
      genetic homogeneity of iPSC and ESC lines by reanalyzing microarray gene
      expression data from seven different laboratories. Unexpectedly, this analysis
      revealed a strong correlation between gene expression signatures and specific
      laboratories in both ESC and iPSC lines. Nearly one-third of the genes with lab
      specific expression signatures are also differentially expressed between ESCs and
      iPSCs. These data are consistent with the hypothesis that in vitro
      microenvironmental context differentially impacts the gene expression signatures
      of both iPSCs and ESCs.

PMID- 20682452
TI  - Molecular analyses of human induced pluripotent stem cells and embryonic stem
      cells.
AB  - Recent work from our group and others has argued that human induced pluripotent
      stem cells (hiPSCs) generated by the introduction of four viruses bearing
      reprogramming factors differ from human embryonic stem cells (hESCs) at the level
      of gene expression (Chin et al., 2009). Many of the differences seen were common
      across independent labs and, at least to some extent, are thought to be a result
      of residual expression of donor cell-specific genes (Chin et al., 2009; Ghosh et
      al., 2010; Marchetto et al., 2009). Two new reports reanalyze similar expression
      data sets as those used in Chin et al. (2009) and come to different conclusions
      (Newman and Cooper, 2010; Guenther et al., 2010). We compare various approaches
      to perform gene expression meta-analysis that all support our original
      conclusions and present new data to demonstrate that polycistronic delivery of
      the reprogramming factors and extended culture brings hiPSCs transcriptionally
      closer to hESCs.

PMID- 20682453
TI  - A probabilistic threshold model: analyzing semantic categorization data with the
      Rasch model.
AB  - According to the Threshold Theory (Hampton, 1995, 2007) semantic categorization
      decisions come about through the placement of a threshold criterion along a
      dimension that represents items' similarity to the category representation. The
      adequacy of this theory is assessed by applying a formalization of the theory,
      known as the Rasch model (Rasch, 1960; Thissen & Steinberg, 1986), to
      categorization data for eight natural language categories and subjecting it to a
      formal test. In validating the model special care is given to its ability to
      account for inter- and intra-individual differences in categorization and their
      relationship with item typicality. Extensions of the Rasch model that can be used
      to uncover the nature of category representations and the sources of
      categorization differences are discussed.

PMID- 20682454
TI  - In vitro effects of detergent sclerosants on fibrinolytic enzymes and inhibitors.
AB  - OBJECTIVE: To investigate the effects of Sodium Tetradecyl Sulphate (STS) and
      Polidocanol (POL) on fibrinolytic mechanisms. MATERIALS AND METHODS: Measurements
      were done with serial dilutions of sclerosants in whole blood (WB), platelet rich
      (PRP) and platelet poor plasma (PPP). Control experiments were done in 5% bovine
      serum albumin (BSA), spiked with the enzyme/inhibitor. Plasminogen was measured
      with a chromogenic assay. Alpha-2-antiplasmin (AP) activity, plasmin-alpha-2
      antiplasmin (PAP) complexes, plasminogen activator inhibitor-1 (PAI-1) activity,
      tissue plasminogen activator (t-PA) total antigen, t-PA activity, t-PA/PAI-1
      complexes, thrombin activatable fibrinolysis inhibitor (TAFI) antigen and
      activated TAFI (TAFIa) were measured by ELISA. RESULTS: At high concentrations
      (>0.3%), STS destroyed plasminogen, PAI-1, t-PA/PAI-1 complexes and total t-PA
      antigen but increased t-PA activity. At low concentrations (<0.3%), both agents
      reduced PAP complexes while increasing AP activity. Low concentration STS
      increased PAI-1 activity, t-PA/PAI-1 complexes, TAFI and TAFIa. Low concentration
      POL mildly increased the total t-PA antigen and TAFI. CONCLUSION: At low
      concentrations, both agents demonstrated a prothrombotic, antifibrinolytic
      (increase in PAI-1, total t-PA antigen, AP, TAFI and TAFIa) activity. At high
      concentrations, STS demonstrated non-prothrombotic (destruction of PAI-1, t
      PA/PAI-1 complexes), antifibrinolytic (destruction of plasminogen, increase in
      AP) activity while POL had minimal effect.

PMID- 20682455
TI  - Three dimensional dental epithelial-mesenchymal constructs of predetermined size
      and shape for tooth regeneration.
AB  - While it is known that precise dental epithelial-mesenchymal (DE-DM) cell
      interactions provide critical functions in tooth development, reliable methods to
      establish proper DE-DM cell interactions for tooth regeneration have yet to be
      established. To address this challenge, and to generate bioengineered teeth of
      predetermined size and shape, in this study, we characterize three dimensional
      (3D) pre-fabricated DE-DM cell constructs. Human dental pulp cell seeded Collagen
      gel layers were co-cultured with porcine DE cells suspended in Growth Factor
      Reduced (GFR) Matrigel. The resulting 3D DE-DM cell layers were cultured in
      vitro, or implanted and grown subcutaneously in vivo in nude rats. Molecular,
      histological and immunohistochemical (IHC) analyses of harvested implants
      revealed organized DE-DM cell interactions, the induced expression of dental
      tissue-specific markers Amelogenin (AM) and Dentin Sialophosphoprotein (DSPP),
      and basement membrane markers Laminin 5 and collagen IV, and irregular
      mineralized tissue formation after 4 weeks. We anticipate that these studies will
      facilitate the eventual establishment of reliable methods to elaborate dental
      tissues, and full sized teeth of specified sized and shape.

PMID- 20682456
TI  - Updated meta-analyses reveal thalamus volume reduction in patients with first
      episode and chronic schizophrenia.
AB  - OBJECTIVES: Although several structural MRI studies report significant thalamus
      volume reduction in patients with schizophrenia, many other studies do not.
      Therefore, the present meta-analyses aimed to clarify whether a reduction in
      thalamic volume characterizes patients diagnosed with schizophrenia by
      considering first-episode and chronic phases of the illness and right and left
      thalamus separately. METHODS: Using Pubmed databases, we made a detailed
      literature search for structural MRI studies on patients with schizophrenia that
      reported physical volumetric measures of the right and left thalamus. Thirteen
      structural MRI studies were considered eligible for meta-analysis of the entire
      sample of patients and of the healthy control subjects. Individual meta-analyses
      were also performed on 6 studies of first-episode patients only and on 7 studies
      of chronic patients only. These were followed by additional meta-analyses to
      investigate the role of the factors "illness phase" and "side" on thalamic volume
      reduction. RESULTS: Overall, the patient group showed a significant bilateral
      thalamus volume reduction compared to healthy control subjects. This was found in
      both first-episode and chronic patients. Furthermore, left thalamus was smaller
      than right in both patients and healthy control subjects. CONCLUSIONS: When only
      studies that used physical volumetric measures were considered, the present meta
      analyses confirmed that thalamic volume reduction characterizes patients with
      schizophrenia, both at the first-episode and chronic phases of the illness.

PMID- 20682458
TI  - From Brentano to mirror neurons: bridging phenomenology and clinical
      neuroscience.

PMID- 20682459
TI  - Coexpression of double or triple copies of the rabies virus glycoprotein gene
      using a 'self-cleaving' 2A peptide-based replication-defective human adenovirus
      serotype 5 vector.
AB  - Rabies virus glycoprotein (RVG) is a major structural protein and antigen of
      rabies virus that induces a highly immunogenic response. In the present study, we
      have used 2A self-cleaving sequence of the foot-and-mouth disease virus (FMDV) to
      express double or triple copies of the RVG from a single open reading frame
      derived from human adenovirus 5 (AdHu5). The recombinant adenoviruses produce
      similar virus titers, indicating that the insertion of double or triple copies of
      the RVG gene linked with the FMDV 2A sequence does not affect virus replication.
      The RVG was efficiently expressed by constructs containing the 2A sequence and
      retained its antigenic property. The 2A self-cleaving peptide mediated efficient
      generation of individual glycoprotein in transient expression assay and did not
      lead to an altered surface distribution of RVG. Flow cytometry demonstrated that
      the expression levels of RVG were improved in recombinant Ads carrying multiple
      RVG gene copies. We conclude that ribosome skipping induced by the FMDV 2A
      sequence is an effective strategy to express multiple glycoprotein genes of
      rabies virus in adenoviruses and 2A-containing recombinant Ads may represent an
      attractive alternative to other coexpression strategies for multiple gene
      expression.

PMID- 20682457
TI  - Smoking-induced change in intrasynaptic dopamine concentration: effect of
      treatment for Tobacco Dependence.
AB  - The aim of this study was to determine whether standard treatments for Tobacco
      Dependence affect smoking-induced changes in intrasynaptic dopamine (DA)
      concentration. Forty-three otherwise healthy adult cigarette smokers (10 to 40
      cigarettes per day) were treated with either practical group counseling (PGC)
      psychotherapy (n=14), bupropion HCl (n=14), or matching pill placebo (n=15)
      (random assignment) for 8 weeks. Before and after treatment, each subject
      underwent a bolus-plus-continuous-infusion (11)C-raclopride positron emission
      tomography (PET) scanning session, during which he or she smoked a regular
      cigarette. The PET scanning outcome measure of interest was percent change in
      smoking-induced (11)C-raclopride binding potential (BP(ND)) in the ventral
      caudate/nucleus accumbens (VCD/NAc), as an indirect measure of DA release.
      Although the entire study sample had a smaller mean smoking-induced reduction in
      VCD/NAc BP(ND) after treatment (compared to before treatment), this change was
      highly correlated with smaller total cigarette puff volumes (and not other
      treatment variables). These data indicate that smoking-induced DA release is dose
      dependent, and is not significantly affected by reductions in daily smoking
      levels or treatment type.

PMID- 20682460
TI  - l-arginine:glycine amidinotransferase (AGAT) deficiency: clinical presentation
      and response to treatment in two patients with a novel mutation.
AB  - Creatine and creatine phosphate provide storage and transmission of phosphate
      bound energy in muscle and brain. Of the three inborn errors of creatine
      metabolism causing brain creatine depletion, l-arginine:glycine
      amidinotransferase (AGAT) deficiency has been described in only two families. We
      describe clinical and biochemical features, magnetic resonance spectroscopy (MRS)
      findings and response to creatine supplementation in two siblings with a novel
      mutation in the AGAT-encoding GATM gene. The sister and brother were evaluated at
      age 12 and 18years, respectively, because of mild mental retardation, muscle
      weakness and low weight. Extensive work-up had previously yielded negative
      results. Electron microscopy of the muscle revealed tubular aggregates and the
      activity of respiratory chain complexes was decreased in the muscle. Urine
      organic acid concentrations normalized to urine creatinine concentration were all
      increased, suggesting a creatine metabolism disorder. Brain MRS was remarkable
      for absence of creatine. Urine guanidinoacetate levels by tandem mass
      spectrometry were low, suggesting AGAT deficiency. GATM sequencing revealed a
      homozygous single nucleotide insertion 1111_1112insA, producing a frame-shift at
      Met-371 and premature termination at codon 376. Eleven months after commencing
      treatment with oral creatine monohydrate 100mg/kg/day, repeat MRI/MRS showed
      significantly increased brain creatine in the sister and a slight increase in the
      older brother. The parents' impression of improved strength and stamina was
      substantiated by increased post-treatment versus pre-treatment scores in the
      Vineland Adaptive Behavior Scale, straight-arm raising and timed up-and-go tests.
      Similarly, there was an apparent improvement in cognitive function, with
      significantly increased IQ-scores in the sister and marginal improvement in the
      brother.

PMID- 20682461
TI  - Obesity in mammaplasty: a study of complications following breast reduction.
AB  - BACKGROUND: Access to effective surgical treatments such as breast reduction is
      often restricted on the grounds of patient obesity. However, there is a lack of
      unambiguous data on the surgical risks of obesity in patients undergoing breast
      reduction. The aim of this study was to assess the relationship between patient
      obesity, as determined by body mass index (BMI), and surgical outcome following
      bilateral breast reduction (BBR). METHODS: Retrospective review of case notes was
      conducted for 306 patients who underwent BBR in our unit over a 5-year period.
      BMI, resection weight, smoking history, technique, complications and outcomes
      were determined from records of follow-up assessment. RESULTS: Overall
      complication rate was 53.9%, with multiple complications of 22.9%. A significant
      increase in complications after BBR with increasing BMI was identified (p = 0.019
      any complication, p = 0.002 multiple complications). The effect of BMI on
      multiple complications was significant and independent of resection weight (p =
      0.031) and reduction technique (p = 0.020). Smoking was associated with higher
      wound dehiscence and multiple complications. We developed a model for predicting
      risk of complications based on key variables. Despite higher complications, there
      was no significant difference in aesthetic outcome at follow-up between the BMI
      groups. CONCLUSIONS: These findings add to the body of evidence that obesity is
      associated with an increased risk of post-operative complications. This has
      implications for surgeons and healthcare payers. However the majority of
      complications were minor and aesthetic outcomes were satisfactory in the majority
      of cases. The use of a 'target' BMI as exclusion criteria should therefore be
      treated with caution.

PMID- 20682462
TI  - Epicanthoplasty with double eyelidplasty incorporating modified Z-plasty for
      Chinese patients.
AB  - BACKGROUND: Blepharoplasty, without correction of the epicanthal folds, weakens
      the aesthetic appearance of the results. Hence, a modified Z-plasty procedure
      with double eyelidplasty was carried out for different degrees of epicanthus.
      METHODS: From 2005 to 2010, the authors performed epicanthoplasties using the
      modified Z-plasty and double eyelidplasty for 322 Chinese patients. The
      conventional double eyelidplasty incisions were made with conterminous modified
      'Z' formation on the medial canthus as well as cutting off the malpositioned
      superficial head of preseptal musculus orbicularis oculi. RESULTS:
      Epicanthoplasty, using this technique, showed good results in most cases. There
      were no recurrences of the epicanthal fold and the scars were inconspicuous.
      CONCLUSION: The modified 'Z' plasty is indicated for all types and degrees of
      medial epicanthi, except epicanthus inversus. The easy design and operation, and
      the excellent and reproducible results satisfy both the plastic surgeons and the
      Chinese patients.

PMID- 20682463
TI  - Comparative study of mature and zymogen mite cysteine protease stability and pH
      unfolding.
AB  - BACKGROUND: Papain-like proteases (CA1) are synthesized as inactive precursors
      carrying an N-terminal propeptide, which is further removed under acidic
      conditions to generate active enzymes. METHODS: To have a better insight into the
      mechanism of activation of this protease family, we compared the pH unfolding of
      the zymogen and the mature form of the mite cysteine protease Der p 1. RESULTS:
      We showed that the presence of the propeptide does not significantly influence
      the pH-induced unfolding of the catalytic domain but does affect its fluorescence
      properties by modifying the exposure of the tryptophan 192 to the solvent. In
      addition, we demonstrated that the propeptide displays weaker pH stability than
      the protease domain confirming that the unfolding of the propeptide is the key
      event in the activation process of the zymogen. GENERAL SIGNIFICANCE: Finally, we
      show, using thermal denaturation and enzymatic activity measurements, that
      whatever the pH value, the propeptide does not stabilize the structure of the
      catalytic domain but very interestingly, prevents its autolysis.

PMID- 20682464
TI  - Multiple retinoic acid response elements cooperate to enhance the inducibility of
      CYP26A1 gene expression in liver.
AB  - CYP26A1, which catalyzes the oxidation of all-trans (at)-retinoic acid (RA), is
      induced moderately by RA in numerous tissues, but is highly responsive in liver.
      To understand this difference, we have examined the CYP26A1 gene sequence,
      identified multiple RA response elements (RAREs) and tested them functionally in
      HepG2 cells as model hepatocytes, and in the liver of vitamin A (VA)-adequate and
      -deficient rats. Analysis of a 2.2 kbp 5'-flanking region upstream of the CYP26A1
      transcription start site (TSS) identified 3 conserved hexameric direct repeat-5
      elements, RARE1, -2 and -3, and a half site, RARE4. The full-length promoter
      containing all 4 elements was sufficient and necessary to increase promoter
      activity similar to levels of endogenous CYP26A1 mRNA produced in HepG2 cells
      treated with at-RA. In DNA binding and chromatin immunoprecipitation assays, the
      binding of RARs to the proximal RARE1 and distal RARE2, -3, and -4 regions of the
      CYP26A1 promoter was increased in RA-treated HepG2 cells, and greater in VA
      sufficient than VA-deficient liver. Moreover, RA increased the binding of RNA
      polymerase-II in the distal as well as the proximal region, indicating that the
      distal region may be looped to become positioned close to the TSS, a process
      favored by retinoic acid receptors. The results support a cooperative model in
      which the functioning of multiple RAREs may account for the strong inducibility
      of CYP26A1 in liver, which, in turn, may be important physiologically for
      restoring retinoid homeostasis when the concentration of RA rises.

PMID- 20682465
TI  - Prevalence and prevention of severe complications of hypohidrotic ectodermal
      dysplasia in infancy.
AB  - OBJECTIVE: To re-evaluate the mortality of hypohidrotic ectodermal dysplasia
      (HED) and the prevalence of hyperpyrexia and possible neurological sequelae in
      affected infants. STUDY DESIGN: A cross-sectional postal survey was conducted
      among parents of 100 children with ectodermal dysplasia who had been registered
      with the German-Swiss-Austrian patient support group at any time point within the
      past 10 years. Detailed questionnaires referring to the first year of life were
      evaluated statistically. RESULTS: 63% of parents returned completed surveys,
      identifying 57% of children as patients with X-linked HED and 20% as patients
      with autosomal HED or HED of unknown origin. Of those two groups, 17 infants had
      been placed in an incubator after birth, where body temperature recording proved
      to be of utmost importance. In 94% of all HED patients, episodes of unexplained
      fever were observed during the first year of life. X-linked HED was associated
      with frequent airway infections. Febrile seizures occurred in 5.9% of infants
      with X-linked HED and in 17% of the other HED patients. Developmental retardation
      was reported for 15% and 25%, respectively. Prognosis depended on the type of
      genetic defect and the time point of diagnosis. Except for one all patients
      survived infancy. Early recognition of the disease was aided by vigilant neonatal
      care and consulting a dermatologist or geneticist. Adequate instruction of the
      parents and networking with patient support groups also reduced the risks
      associated with HED. CONCLUSIONS: Today, mortality of HED and the risk of
      hyperthermic brain damage are still increased, but lower than reported
      previously.

PMID- 20682466
TI  - A new alpha(0)-thalassemia deletion found in a Dutch family (--(AW)).
AB  - Alpha-thalassemia is an inherited hemoglobin disorder characterized by a
      microcytic hypochromic anemia caused by a quantitative reduction of the alpha
      globin chain. The majority of the alpha-thalassemias is caused by deletions in
      the alpha-globin gene cluster. A deletion in the alpha-globin gene cluster, which
      was found in a Dutch family, was characterized by MLPA, long-range PCR and direct
      sequencing. We describe the molecular characterization of a novel 8.2kb deletion
      (--(AW)), involving both alpha-globin genes in cis. The deletion is caused by a
      non-homologous recombination event between an Alu and an L1-repeat sequence. This
      deletion is the third example of a non-homologous recombination event involving
      an Alu and an L1 repeat, and the first described in the human alpha-globin gene
      cluster. Because of a 25% risk of Hb Bart's with hydrops foetalis in the
      offspring when in combination with another alpha(0)-thalassemia allele, it is
      important to diagnose this deletion.

PMID- 20682467
TI  - Efficient tools for comparative substring analysis.
AB  - This paper introduces an efficient implementation of approaches to alignment-free
      comparative genome analysis and genome-based phylogeny relying on substring
      composition. Distances derived from substring statistics have been proposed
      recently as a meaningful alternative to distances derived from sequence
      alignment. In particular, procaryote phylogenies based on comparative 5- and 6
      mer analysis of whole proteomes have successfully been worked out. The present
      implementation extends the computation of composition-based distances so as to
      involve allk-mers for anyk up to any preset m aximum length K (including
      K=infinity). Remarkably, although there may be Theta(L(2)) distinct strings that
      occur in a given sequence of length L (and Theta(KL) of length k< or =K), it is
      shown that composition-based distances as well as many other details of interest
      in comparative genome analysis can be computed in O(L) time and space (with a
      constant that is independent of the size of K, that is, the same constant works
      for all K). A typical run with 2 sequences of altogether 1.5 million characters
      computes their composition-based distance in about 2s, a performance to be
      contrasted with the several hours needed, even when restricting attention to
      substrings of length at most 6, by the direct method in use. This paper.

PMID- 20682468
TI  - On the selection of weight decay parameter for faulty networks.
AB  - The weight-decay technique is an effective approach to handle overfitting and
      weight fault. For fault-free networks, without an appropriate value of decay
      parameter, the trained network is either overfitted or underfitted. However, many
      existing results on the selection of decay parameter focus on fault-free networks
      only. It is well known that the weight-decay method can also suppress the effect
      of weight fault. For the faulty case, using a test set to select the decay
      parameter is not practice because there are huge number of possible faulty
      networks for a trained network. This paper develops two mean prediction error
      (MPE) formulae for predicting the performance of faulty radial basis function
      (RBF) networks. Two fault models, multiplicative weight noise and open weight
      fault, are considered. Our MPE formulae involve the training error and trained
      weights only. Besides, in our method, we do not need to generate a huge number of
      faulty networks to measure the test error for the fault situation. The MPE
      formulae allow us to select appropriate values of decay parameter for faulty
      networks. Our experiments showed that, although there are small differences
      between the true test errors (from the test set) and the MPE values, the MPE
      formulae can accurately locate the appropriate value of the decay parameter for
      minimizing the true test error of faulty networks.

PMID- 20682469
TI  - On the stability of the n:m phase synchronization index.
AB  - Synchronization analysis of multitrial EEG or (magneto encephalogram) MEG signals
      is an excellent approach to detect functional connectivity between different
      neuronal oscillators. In our current research, the n:m phase synchronization
      index (n:m PSI ) is of special interest. We prove the existence of stable and
      unstable synchronies dependent upon the analysis frequencies and show that they
      lie closely together in the frequency domain. Thus, a plot of the time-frequency
      plane of the n:m PSI automatically violates the sampling theorem and accordingly,
      the method cannot be considered as a black box. A frequency-tiling approach is
      presented that can detect robust synchronies while ignoring the unstable ones.
      The improved synchrony detection is evaluated in numerical experiments on using
      both simulated and real-life data. It can be demonstrated that the transient
      synchronization events between MEG oscillations in distant frequency ranges can
      be detected and that compactly textured EEG synchronization patterns can be
      reliably characterized.

PMID- 20682470
TI  - Sufficient statistics as a generalization of binning in spectral X-ray imaging.
AB  - It is well known that the energy dependence of X-ray attenuation can be used to
      characterize materials. Yet, even with energy discriminating photon counting X
      ray detectors, it is still unclear how to best form energy dependent measurements
      for spectral imaging. Common ideas include binning photon counts based on their
      energies and detectors with both photon counting and energy integrating
      electronics. These approaches can be generalized to energy weighted measurements,
      which we prove can form a sufficient statistic for spectral X-ray imaging if the
      weights used, which we term MU-weights, are basis attenuation functions that can
      also be used for material decomposition. To study the performance of these
      different methods, we evaluate the Cramer-Rao lower bound (CRLB) of material
      estimates in the presence of quantum noise. We found that the choice of binning
      and weighting schemes can greatly affect the performance of material
      decomposition. Even with optimized thresholds, binning condenses information but
      incurs penalties to decomposition precision and is not robust to changes in the
      source spectrum or object size, although this can be mitigated by adding more
      bins or removing photons of certain energies from the spectrum. On the other
      hand, because MU-weighted measurements form a sufficient statistic for spectral
      imaging, the CRLB of the material decomposition estimates is identical to the
      quantum noise limited performance of a system with complete energy information of
      all photons. Finally, we show that MU-weights lead to increased conspicuity over
      other methods in a simulated calcium contrast experiment.

PMID- 20682471
TI  - A neural network of smooth hinge functions.
AB  - Smooth hinging hyperplane (SHH) has been proposed as an improvement over the well
      known hinging hyperplane (HH) by the fact that it retains the useful features of
      HH while overcoming HH's drawback of nondifferentiability. This paper introduces
      a formal characterization of smooth hinge function (SHF), which can be used to
      generate SHH as a neural network. A method for the general construction of SHF is
      also given. Furthermore, the work proves that SHH is better than HH in functional
      approximation, i.e., the optimal error of SHH approximating a general function is
      always smaller or equal to that of HH. Particularly, in the case that the SHF is
      generated via the integration of a class of sigmoidal functions, it is further
      proven that the corresponding SHH of the 2m SHFs would outperform a neural
      network with m of the sigmoidal function from which the SHF is derived. Any upper
      bound established on the approximation error of a neural network of m sigmoidal
      activation functions can hence be translated to the SHH of m SHFs by replacing m
      with [m/2]. The work also includes an algorithm for the identification of SHH
      making use of its differentiability property. Simulation experiments are
      presented to validate the theoretical conclusions to possible extent.

PMID- 20682472
TI  - Light field analysis for modeling image formation.
AB  - Image formation is traditionally described by a number of individual models, one
      for each specific effect in the image formation process. However, it is difficult
      to aggregate the effects by concatenating such individual models. In this paper,
      we apply light transport analysis to derive a unified image formation model that
      represents the radiance along a light ray as a 4-D light field signal and
      physical phenomena such as lens refraction and blocking as linear transformations
      or modulations of the light field. This unified mathematical framework allows the
      entire image formation process to be elegantly described by a single equation. It
      also allows most geometric and photometric effects of imaging, including
      perspective transformation, defocus blur, and vignetting, to be represented in
      both 4-D primal and dual domains. The result matches that of traditional models.
      Generalizations and applications of this theoretic framework are discussed.

PMID- 20682473
TI  - A stratified approach for camera calibration using spheres.
AB  - This paper proposes a stratified approach for camera calibration using spheres.
      Previous works have exploited epipolar tangents to locate frontier points on
      spheres for estimating the epipolar geometry. It is shown in this paper that
      other than the frontier points, two additional point features can be obtained by
      considering the bitangent envelopes of a pair of spheres. A simple method for
      locating the images of such point features and the sphere centers is presented.
      An algorithm for recovering the fundamental matrix in a plane plus parallax
      representation using these recovered image points and the epipolar tangents from
      three spheres is developed. A new formulation of the absolute dual quadric as a
      cone tangent to a dual sphere with the plane at infinity being its vertex is
      derived. This allows the recovery of the absolute dual quadric, which is used to
      upgrade the weak calibration to a full calibration. Experimental results on both
      synthetic and real data are presented, which demonstrate the feasibility and the
      high precision achieved by our proposed algorithm.

PMID- 20682474
TI  - Quality assessment of deblocked images.
AB  - We study the efficiency of deblocking algorithms for improving visual signals
      degraded by blocking artifacts from compression. Rather than using only the
      perceptually questionable PSNR, we instead propose a block-sensitive index, named
      PSNR-B, that produces objective judgments that accord with observations. The PSNR
      B modifies PSNR by including a blocking effect factor. We also use the
      perceptually significant SSIM index, which produces results largely in agreement
      with PSNR-B. Simulation results show that the PSNR-B results in better
      performance for quality assessment of deblocked images than PSNR and a well-known
      blockiness-specific index.

PMID- 20682475
TI  - Modeling cognitive loads for evolving shared mental models in human-agent
      collaboration.
AB  - Recent research on human-centered teamwork highly demands the design of cognitive
      agents that can model and exploit human partners' cognitive load to enhance team
      performance. In this paper, we focus on teams composed of human-agent pairs and
      develop a system called Shared Mental Models for all--SMMall. SMMall implements a
      hidden Markov model (HMM)-based cognitive load model for an agent to predict its
      human partner's instantaneous cognitive load status. It also implements a user
      interface (UI) concept called shared belief map, which offers a synergic
      representation of team members' information space and allows them to share
      beliefs. An experiment was conducted to evaluate the HMM-based load models. The
      results indicate that the HMM-based load models are effective in helping team
      members develop a shared mental model (SMM), and the benefit of load-based
      information sharing becomes more significant as communication capacity increases.
      It also suggests that multiparty communication plays an important role in
      forming/evolving team SMMs, and when a group of agents can be partitioned into
      subteams, splitting messages by their load status can be more effective for
      developing subteam SMMs.

PMID- 20682476
TI  - Fecundability and serum PBDE concentrations in women.

PMID- 20682477
TI  - Probabilistic modeling of dietary arsenic exposure.

PMID- 20682480
TI  - The Salmonella mutagenicity assay: the stethoscope of genetic toxicology for the
      21st century.
AB  - OBJECTIVES: According to the 2007 National Research Council report Toxicology for
      the Twenty-First Century, modern methods (e.g., "omics," in vitro assays, high
      throughput testing, computational methods) will lead to the emergence of a new
      approach to toxicology. The Salmonella mammalian microsome mutagenicity assay has
      been central to the field of genetic toxicology since the 1970s. Here we document
      the paradigm shifts engendered by the assay, the validation and applications of
      the assay, and how the assay is a model for future in vitro toxicology assays.
      DATA SOURCES: We searched PubMed, Scopus, and Web of Knowledge using key words
      relevant to the Salmonella assay and additional genotoxicity assays. DATA
      EXTRACTION: We merged the citations, removing duplicates, and categorized the
      papers by year and topic. DATA SYNTHESIS: The Salmonella assay led to two
      paradigm shifts: that some carcinogens were mutagens and that some environmental
      samples (e.g., air, water, soil, food, combustion emissions) were mutagenic.
      Although there are > 10,000 publications on the Salmonella assay, covering tens
      of thousands of agents, data on even more agents probably exist in unpublished
      form, largely as proprietary studies by industry. The Salmonella assay is a model
      for the development of 21st century in vitro toxicology assays in terms of the
      establishment of standard procedures, ability to test various agents,
      transferability across laboratories, validation and testing, and structure
      activity analysis. CONCLUSIONS: Similar to a stethoscope as a first-line,
      inexpensive tool in medicine, the Salmonella assay can serve a similar,
      indispensable role in the foreseeable future of 21st century toxicology.

PMID- 20682482
TI  - [The epilepsy treatment gap in six primary care centres in Togo (2007-2009)].
AB  - Epilepsy, the most common serious neurological condition, is one of the most
      widespread non-transmissible diseases in the world. In developing countries,
      about 90% of those with epilepsy do not receive appropriate treatment; this
      treatment gap, very high compared with other chronic diseases, helps to explain
      the marginalisation and poor living conditions of these people. Reducing this
      treatment gap and the burden that epilepsy represents is a difficult task and the
      obstacles are numerous. The cultural attitudes, the absence of priority for this
      disease, the weak health infrastructure and the insufficient supply of anti
      epileptics are just some of the factors that prevent adequate treatment. The
      extent of this problem led WHO and the International League against Epilepsy to
      launch an international campaign in June 1997 to bring epilepsy "out from the
      shadows". We sought to evaluate a strategy of community-based care for epilepsy
      in the six pilot districts. This strategy consisted in reducing the treatment gap
      in six local primary care units (PCUs) and then spreading the programme to
      surrounding PCUs, the entire district and then the entire region. This
      prospective evaluation study, which took place from May 2008 to July 2009,
      applied many strategies. WHO/AFRO made available funding of USD 3500 a year. A
      training meeting was held for PCU staff and community health agents, and numerous
      meetings from May 2007 through March 2008 aimed to increase awareness and
      motivation. The National Program for Mental Health (NPMH) ensured the
      availability of a permanent supply of anti-epileptics. Monitoring with
      supervision of activities and evaluation were conducted during and at the end of
      the process by the members of the Lome Hospital neurology team and the management
      team of every district. Community-based management of 816 people with epilepsy
      over a period of 15 months was assessed internally. The planned strategies were
      conducted. The sex ratio (M/W) was 1.10. Treatment adhesion ranged from 96% to
      99%. Mortality was 9%. The treatment gap in the PCUs, which varied from 98% to
      94% in May 2008 fell by July 2009, ranging from only 40% to 25%. The "good
      practice" of accepting and treating patients with epilepsy in these areas where
      traditional culture excludes them from the community demanded the local
      acceptance of responsibility -- both medical and psychosocial. The reduction in
      epilepsy attacks and the integration of 2 or 3 patients in a community sufficed
      to bring other people with epilepsy out from the shadows. These successes show
      that in developing countries, it is possible to improve the health of different
      populations when these projects are integrated into primary health care. Positive
      results, and specifically a treatment gap below 50%, were obtained in all six
      PCUs. These results, acquired after months of activity, contributed to decrease
      the stigmatisation of epilepsy. Maintaining this reduction in the treatment gap
      requires continuation of the struggle against epilepsy and permanent improvement
      of primary health care. The often unplanned moves of staff and the reluctance of
      district and regional health managers to allocate resources to the project to
      perpetuate the programme constitute major difficulties. It appears urgent to
      adopt an active policy for providing care of patients with epilepsy in Africa in
      order to increase their lifespan.

PMID- 20682483
TI  - [Management for 145 cases of Merkel cell carcinoma].
AB  - PURPOSE: Merkel cell carcinoma (MCC)/primary cutaneous neuroendocrine carcinoma
      is a rare and aggressive malignant tumor. Optimal therapeutic strategy has not
      yet been established. PATIENTS AND METHODS: Management of 145 patients from five
      centres was analysed. These data included ages, pathological stages, disease
      sites, histological and treatment details. Cause-specific (CSS) and overall
      survivals (OS) were analyzed by the Log-rank and Kaplan-Meier methods. RESULTS:
      Median age was 78 years (47-95.2). We experienced 37 local, 37 regional and 15
      distant relapses. In case of relapse, salvage therapy has been proposed whenever
      the general state of health condition of patient permitted it. CONCLUSION: Our
      results for the treatment of relapse encourage multidisciplinary approach.
      Multicenter prospective trials are still needed to clarify and validate the
      optimal strategy.

PMID- 20682481
TI  - An emerging role for epigenetic dysregulation in arsenic toxicity and
      carcinogenesis.
AB  - BACKGROUND: Exposure to arsenic, an established human carcinogen, through
      consumption of highly contaminated drinking water is a worldwide public health
      concern. Several mechanisms by which arsenical compounds induce tumorigenesis
      have been proposed, including oxidative stress, genotoxic damage, and chromosomal
      abnormalities. Recent studies have suggested that epigenetic mechanisms may also
      mediate toxicity and carcinogenicity resulting from arsenic exposure. OBJECTIVE:
      We examined the evidence supporting the roles of the three major epigenetic
      mechanisms-DNA methylation, histone modification, and microRNA (miRNA) expression
      in arsenic toxicity and, in particular, carcinogenicity. We also investigated
      future research directions necessary to clarify epigenetic and other mechanisms
      in humans. DATA SOURCES AND SYNTHESIS: We conducted a PubMed search of arsenic
      exposure and epigenetic modification through April 2010 and summarized the in
      vitro and in vivo research findings, from both our group and others, on arsenic
      associated epigenetic alteration and its potential role in toxicity and
      carcinogenicity. CONCLUSIONS: Arsenic exposure has been shown to alter
      methylation levels of both global DNA and gene promoters; histone acetylation,
      methylation, and phosphorylation; and miRNA expression, in studies analyzing
      mainly a limited number of epigenetic end points. Systematic epigenomic studies
      in human populations exposed to arsenic or in patients with arsenic-associated
      cancer have not yet been performed. Such studies would help to elucidate the
      relationship between arsenic exposure, epigenetic dysregulation, and
      carcinogenesis and are becoming feasible because of recent technological
      advancements.

PMID- 20682484
TI  - [Cost of stroke in Lome (Togo).]
AB  - The financial crisis that affected the healthcare systems of most developing
      countries in the 1980s, the ensuing need to control hospital costs, the partial
      disengagement of States, and the resort to policies based on cost recovery -- all
      these led to the restructuring of hospital systems in Africa, in accordance with
      the Bamako initiative, adopted by the WHO regional committee in September 1987.
      This restructuring required populations to pay much of the cost of their health
      care. In practice, however, the major obstacle to this policy of cost recovery
      remains poverty. Twenty years after the adoption of this initiative, we sought to
      evaluate the cost of hospitalisation for cerebral stroke in Togo, where there is
      no national health insurance programme, and to propose strategies to improve its
      management. This prospective study was conducted in the neurology department of
      the University Hospital of Lome over a period of 12 months, from 1 January to 31
      December 2005 and included 412 consecutive patients with a confirmed diagnosis
      according to WHO criteria and cerebral computed tomography (CT) results. This
      department has 30 beds in rooms categorized according to their cost to the
      patients: EUR 27.30 for a superior single room, EUR 18.20 for the first category
      standard room, EUR 13.7 euros for the second, and EUR 8.20 for the third.
      Patients or their family could choose their room category. Of the 412 patients
      included in our study, 248 (60.2%) had an ischaemic stroke (IS) and 164 (39.8%) a
      haemorrhagic stroke (HS). The average length of stay was 17.4 +/- 10.4 days
      (range: 3 to 41 days), 10.17 days (range: 3 to 24) for IS and 26.7 (range: 13 to
      41) for HS. In all, 124 (30%) patients produced insurance certificates, and 288
      (70%) paid directly; among the latter 152 (36.9%) patients paid their own
      expenses, while relatives paid for 65 (63.10%). Housewives accounted for 136
      (33%) patients, 96 (23%) retired and 180 (20.4%) civil servants. No one chose the
      superior quality private room; 256 (62%) patients used category 3 rooms, 68
      (27.2%) of them housewives and 44 (17.2%) retired. The total cost averaged EUR
      679.6 +/- 297.90, almost 19 times higher than the minimum monthly salary of civil
      servants in Togo (EUR 36.30). The total for IS was EUR 428.80 +/- 188.9 and for
      HS, EUR 935.6 +/- 36.50. The average person in Togo spends EUR 3.99 per person
      per year on health, while a stroke patient hospitalized in Lome spends an average
      of 170 times more in only 17.4 days. Accordingly, most of the Togolese cannot
      access specialized neurology care for a stroke. Drug expenses accounted for the
      highest portion of the cost, in part because patients are obliged to buy retail
      pharmaceutical products that could have been provided to them at the hospital.
      Use of generic drugs could reduce this cost. Length of stay and tests could be
      reduced by setting time limits for procedures and setting up rehabilitation
      facilities.

PMID- 20682485
TI  - Effective protection from exposure to environmental tobacco smoke in Poland: The
      World Health Organization perspective.
AB  - Tobacco is the single greatest preventable cause of death in the world today,
      killing approximately half of the people who use it. Several strategies have been
      proved to reduce tobacco use. However, more than 50 years after the health
      effects of smoking were scientifically proven, and more than 20 years after
      evidence confirmed the hazards from exposure to second-hand smoke, few countries
      have implemented effective and recognized strategies to control the tobacco
      epidemic. This paper summarizes the World Health Organization recommendations for
      effective protection from exposure to environmental tobacco smoke along with the
      existing tobacco control programs and legislation in force in Poland.

PMID- 20682486
TI  - Time-period mortality patterns in a Gaseous Diffusion Plant workforce.
AB  - BACKGROUND: We sub-divided a cohort of 6820 workers at the Paducah (KY) Gaseous
      Diffusion Plant (PGDP) which was traced from 1953 to 2003. The subdivisions were
      made to assess the mortality risks in a sub-group of workers employed solely
      during the plant's refit period, a time of suspected higher exposure to metal
      dusts (nickel, arsenic, chromium and uranium) and trichloroethylene. METHODS:
      This article describes a comparison of exposures and causes of death for 754
      workers employed exclusively during the period of 1975-1979, with 1554 workers
      who worked in this period as well as other years. This interval was when the
      gaseous diffusion cascade facilities were re-fit. The workers employed 'only'
      during this period have a variety of deterministic factors (age-at-hire, duration
      of employment) that distinguish this sub-group of employees from the 'long-term'
      workforce. RESULTS: The 'only 1975-1979' workers had a larger fraction of
      minorities and female workers. This 'only' sub-group was disproportionately
      employed in unskilled labor positions. The 'only' workers were younger than the
      referent group, and a 14-year earlier mean age at death. The all-cause mortality
      standardized rate ratio [SRR] was 1.58 [95% Cl: 0.97-2.42]. The 'only' group was
      significantly different from the 'ever' workers with respect to suicides, SRR =
      3.74 [95% Cl: 1.86-6.69], and for homicides, SRR = 11.71 [95% Cl: 3.20-30.03].
      CONCLUSIONS: These elevated mortality risks do not seem to be due to PGDP
      employment exposures to metal dusts or trichloroethylene. Socio-economic factors
      may be a determinant for the patterns of suicides and murders described for this
      sub-group of employees. These findings provide guidance for communities with a
      dominant local employer. Persons who experience short-term hiring may warrant
      public health services to mitigate their risk of tragic deaths. A case-control
      study of these deaths is recommended to clarify individual risk behaviors.

PMID- 20682487
TI  - Changes in the lipid profile of blood serum in women taking sauna baths of
      various duration.
AB  - OBJECTIVES: There is little information on lipid metabolism after sauna treatment
      in the literature. The present research is aimed to determine the influence of
      sauna baths on fat metabolism in young women. MATERIALS AND METHODS: Twenty
      healthy, eumenhorreic, female volunteers (19-21 yr old) were exposed to Finnish
      sauna bath seven times every second day. In group I (n = 10) each time the sauna
      treatment lasted 30 min, whereas in group II (n = 10) 40 min with 5-minute break
      to cool down. Body mass, heart rate and blood pressure were measured before and
      after sauna bath. Rectal temperature was monitored during stay in sauna room.
      Prior to the sauna bath and during its last two minutes the minute oxygen uptake
      and the level of CO2 exhalation were analyzed in the exhaled air, and the
      respiratory quotient RQ was calculated. In the blood samples collected before the
      sauna bath and immediately afterwards hematocrit, hemoglobin, and lipid profile-
      total lipids, free fatty acids, total free fatty acids, triacylglycerols, total
      cholesterol (TC), high density lipids (HDL), low density lipids (LDL) were
      analyzed. RESULTS: Rectal temperature was lower in the last sauna bath than in
      the first one. Losses of plasma were greater during the seventh bath than during
      the first one. Acceleration of the metabolism of lipids occurs after every sauna
      bath. A reduced level of TC and LDLC and a raised level of HDL was observed after
      repeated sauna baths. CONCLUSION: After 2 weeks of repeated sauna session some
      changes in total cholesterol and concentration of LDLC were observed, while
      concentration of HDLC increased after 7th sauna bath in group I. Those kinds of
      changes may be good prognoses of ischemic heart disease prevention, but further
      research on the influence of sauna on fat metabolism is needed.

PMID- 20682488
TI  - Selected risk factors of diabetes mellitus among road transport drivers.
AB  - OBJECTIVES: Road transport drivers are one of the professional groups whose
      activities have a strong impact on public safety. In view of the nature of their
      professional activity, the drivers are at a higher risk of obesity and
      hypertension, and thus, indirectly, of carbohydrate metabolism disorders such as
      diabetes mellitus. MATERIALS AND METHODS: Medical documentation was a source of
      data for the reported study. It derived from medical examinations of truck and
      bus drivers applying for the new category II driving licence or for prolongation
      of the one they already had. RESULTS: Excessive body weight was recorded in 62.6%
      of the study population; 45.3% had overweight and 17.4% were diagnosed with
      obesity. Hypertension was noted in the medical records of 36.7% drivers. The
      prevalence of abnormal BP values was increasing with age. Overweight was found to
      be a risk factor for hypertension. Hyperglycaemia was found in 47.5% of the
      drivers and was also increasing with age. CONCLUSION: In road transport drivers,
      the high prevalence of excessive body weight and elevated arterial blood pressure
      as the risk factors for diabetes indicates a need to undertake multidimensional
      actions targeted on this particular profession and involving various health care
      sectors. Prophylactic and detailed pre-placement examinations should be
      considered, depending on the rate and intensity of the disorders diagnosed. This
      should be coupled with an introduction of primary and secondary prophylactic
      activities and monitoring of relevant treatment. A close collaboration with the
      patient's GP is necessary.

PMID- 20682489
TI  - Influence of the ten sessions of the whole body cryostimulation on aerobic and
      anaerobic capacity.
AB  - OBJECTIVES: The aim of this study was to determine the influence of whole body
      cryostimulation on aerobic and anaerobic capacities. MATERIALS AND METHODS: To
      test the hypothesis that whole body cryostimulation improves physical capacity,
      thirty subjects (fifteen males and fifteen females) undertook two ergocycle
      trials before and after the ten sessions of cryogenic chamber treatment. To
      assess baseline aerobic capacity, the progressive cycle ergometer test was
      applied. This allowed determination of maximal oxygen uptake and ventilatory
      thresholds. Twenty-second Wingate test was performed to assess baseline levels of
      anaerobic power. After finishing the treatments in the cryogenic chamber, the
      exercise protocol was repeated. Before the first, and after the last whole body
      cryostimulation, venous blood samples were drawn to determine basic blood values,
      including levels of erythrocytes, leukocytes and thrombocytes, hemoglobin
      concentration, and hematocrit. RESULTS: There were no changes in aerobic
      capacity, in both females and males, after ten sessions of 3-minute-long
      exposures to cryogenic temperature (-130 degrees C). Participation in the whole
      body cryostimulation caused an increase in maximal anaerobic power in males (from
      11.1 to 11.9 W x kg(-1); P < 0.05), but not in females. CONCLUSIONS: It can be
      concluded that whole body cryostimulation can be beneficial, at least in males,
      for increasing anaerobic capacity in sport disciplines involving speed and
      strength.

PMID- 20682490
TI  - Effects of GSM signals during exposure to event related potentials (ERPs).
AB  - OBJECTIVES: The primary aim of this work was to assess the effect of
      electromagnetic field (EMF) from the GSM mobile phone system on human brain
      function. The assessment was based on the assay of event related potentials
      (ERPs). MATERIAL AND METHODS: The study group consisted of 15 volunteers,
      including 7 men and 8 women. The test protocol comprised determination of P300
      wave in each volunteer during exposure to the EMF. To eliminate possible effects
      of the applied test procedure on the final result, the test was repeated without
      EMF exposure. P300 latency, amplitude, and latency of the N1, N2, P2 waves were
      analysed. RESULTS: The statistical analysis revealed an effect of EMF on P300
      amplitude. In the experiment with EMF exposure, lower P300 amplitudes were
      observed only at the time in which the volunteers were exposed to EMF; when the
      exposure was discontinued, the values of the amplitude were the same as those
      observed before EMF application. No such change was observed when the experiment
      was repeated with sham exposure, which may be considered as an indirect proof
      that lower P300 amplitude values were due to EMF exposure. No statistically
      significant changes were noted in the latencies of the N1, N2, P2 waves that
      precede the P300 wave, nor in the latency of the P300 itself. CONCLUSIONS: The
      results suggest that exposure to GSM EMF exerts some effects on CNS, including
      effects on long latency ERPs.

PMID- 20682491
TI  - Asbestos is still with us: repeat call for a universal ban.
AB  - All forms of asbestos are proven human carcinogens. All forms of asbestos cause
      malignant mesothelioma, lung, and laryngeal cancers, and may cause ovarian,
      gastrointestinal and other cancers. No exposure to asbestos is without risk, and
      there is no safe threshold of exposure to asbestos. Asbestos cancer victims die
      painful lingering deaths. These deaths are almost entirely preventable. When
      evidence of the carcinogenicity of asbestos became incontrovertible, the
      concerned parties, including the Collegium Ramazzini, called for a universal ban
      on the mining, manufacture and use of asbestos in all countries around the world.
      Asbestos is now banned in 52 countries, and safer products have replaced many
      materials that once were made with asbestos. Nonetheless, a large number of
      countries still use, import, and export asbestos and asbestos-containing
      products. And in many countries that have banned other forms of asbestos, the so
      called "controlled use" of chrysotile asbestos continues to be permitted, an
      exemption that has no basis in medical science but rather reflects the political
      and economic influence of the asbestos mining and manufacturing industry. To
      protect the health of all people in the world--industrial workers, construction
      workers, women and children, now and in future generations--the Collegium
      Ramazzini calls again today on all countries of the world, as we have repeatedly
      in the past, to join in the international endeavor to ban all forms of asbestos.
      An international ban on asbestos is urgently needed.

PMID- 20682492
TI  - Complementary and alternative medicine use among women with breast cancer: a
      systematic review.
AB  - Patients with breast cancer use complementary and alternative medicine (CAM)
      despite the fact that no studies have shown altered disease progression
      attributable to CAM use. The purpose of this systematic review is to summarize
      research as it relates to CAM use among women with breast cancer. Among the many
      findings of the review, biologically based practices were noted as the types of
      CAM most used by women with breast cancer, followed by mind-body medicine, whole
      medical systems, and energy medicine. Sources of information about CAM use for
      women with breast cancer vary widely, including family, friends, mass media,
      healthcare providers, CAM providers, and self-help groups. Sociodemographic
      factors that appear to be related to CAM use were younger age, higher education,
      higher income, married status, involvement in a support group, and health
      insurance. The reasons for CAM use reported by women with breast cancer were to
      help healing, to promote emotional health, and to cure cancer. Oncology nurses
      should learn more about CAM use among women with breast cancer. Open
      communication about CAM use helps ensure that safe and holistic care is provided.
      Additional research in this particular area is needed.

PMID- 20682493
TI  - Environmental risks: lessons from the Gulf.

PMID- 20682494
TI  - Imagine: compassion fatigue training for nurses.

PMID- 20682495
TI  - Evidence, not politics, should guide cancer care.

PMID- 20682496
TI  - Evolution of patient navigation.
AB  - The role of nurses in patient navigation has evolved over more than four decades.
      Navigators in cancer care can guide patients through the physical, emotional, and
      financial challenges that come with a diagnosis of cancer and facilitate
      communication among healthcare providers. Navigation has the potential to improve
      patient outcomes and system efficiency. Oncology nurses are well suited to help
      patients with cancer navigate the healthcare system from diagnosis and treatment
      through survivorship and palliative care.

PMID- 20682497
TI  - Idiopathic thrombocytic purpura.
AB  - Oncology nurses often see patients with nononcologic disorders. Idiopathic
      thrombocytic purpura (ITP), a platelet disorder, is one such example. Being both
      an emergent condition as well as a chronic one, nurses will need to assess
      patients with ITP for bleeding and conduct extensive patient education about the
      disease process and treatment options.

PMID- 20682498
TI  - A case study progression to multiple myeloma.
AB  - Multiple myeloma consistently is preceded by precursor states, which often are
      diagnosed incidentally in the laboratory. This case report illustrates the
      clinical dilemma of progression from precursor to full malignancy. The article
      also discusses future directions in management and research focusing on
      myelomagenesis.

PMID- 20682499
TI  - Development of patient education for older adults receiving chemotherapy.
AB  - The diagnosis of cancer is a significant and often overwhelming event. Older
      adults may have age-related physical and cognitive changes in addition to the
      stresses of cancer diagnosis and treatment. The combination can present
      significant barriers to learning readiness in older adults who choose
      chemotherapy. Older adults receiving chemotherapy need to learn self-care for
      risks such as neutropenia; however, patient teaching materials typically are not
      developed with consideration for this group of learners. This article reviews the
      current literature on effective chemotherapy patient education, the physical and
      cognitive changes related to aging learners, and strategies appropriate for
      teaching older adults. As described in this article, best practices were
      synthesized from the literature, and educational materials for teaching basic
      chemotherapy safety practices to older adults were developed. The materials then
      were pilot tested with a select group of older adults receiving chemotherapy, and
      their feedback was incorporated into recommendations for future research and
      practice.

PMID- 20682500
TI  - Perceptions and experiences of patients receiving oral chemotherapy.
AB  - Although many patients prefer orally administered cancer therapy (including oral
      chemotherapy) because of its convenience, the shift from hospital to home-based
      administration creates concerns. This article explores the perceptions and
      experiences of oral chemotherapy users and their caregivers to assess
      vulnerabilities and improvement opportunities at each stage of the medication
      process: choosing oral chemotherapy, prescribing, dispensing, administering, and
      monitoring. The authors recruited 15 current and former oral chemotherapy users,
      as well as caregivers who administered the medications to children, to
      participate in one of two focus group sessions at a comprehensive cancer center.
      Participants largely were satisfied with oral cancer therapy but raised concerns
      regarding their lack of preparedness for side effects and their unfamiliarity
      with the possible techniques to mitigate drug toxicity. Participants also
      described difficulties obtaining medications through retail pharmacies. Parents
      of pediatric patients with cancer indicated concerns regarding their children's
      emotional health and correct medication administration. Participants believed
      that the initial prescribing encounter should have included more education, and
      they also wanted more frequent follow-up by healthcare practitioners. As oral
      cancer therapy is used more widely, oncology healthcare providers will need to
      create robust mechanisms to support their safe use.

PMID- 20682501
TI  - Adherence to oral cancer therapies: nursing interventions.
AB  - This article reviews nursing interventions to increase adherence to oral cancer
      therapies, such as patient and care-partner education, side-effect and medication
      management, and safety issues. Data sources included peer-reviewed nursing and
      medical literature, healthcare Web sites, and published monographs. Oncology
      nurses are uniquely positioned to promote patient adherence to oral cancer
      therapies by ensuring that patients understand the goals of treatment, promoting
      safe prescriptive practices, proactively managing treatment side effects, and
      identifying and resolving underlying barriers to adherence. When adherence is
      optimized, clinical outcomes are greatly improved. Primary responsibility for
      adherence to an oral cancer therapy regimen remains with the patient. Oncology
      nurses, as part of a healthcare team, can have a significant influence on patient
      adherence by providing thorough and timely patient and family education and by
      monitoring and managing side effects of treatment. Monitoring adherence to oral
      cancer therapies is not a recent phenomenon nor limited to oral cancer treatments
      but presents an increasing challenge as additional oral therapies enter the
      marketplace. Oncology nurses should develop and enhance strategies and materials
      for patient education on oral cancer therapies, improve side-effect management,
      assist with patient access to medications, and develop practice guidelines to
      ensure adherence and promote safety.

PMID- 20682502
TI  - The prophylactic use of probiotics in the prevention of radiation therapy-induced
      diarrhea.
AB  - Cancer treatment regimens that include radiation therapy (RT) to the abdominal
      region for cervical, ovarian, prostate, sigmoid, or colorectal cancer potentially
      disturb the colonization resistance of the indigenous gut flora, causing RT
      induced diarrhea, enteritis, and colitis in more than 80% of patients with
      cancer. One approach for the prevention of RT-induced diarrhea is the use of
      probiotics. Randomized clinical trials have demonstrated efficacy of probiotic
      preparations VSL #3 and Lactobacillus casei DN-114 001 in decreasing the
      incidence and grade of RT-induced diarrhea. Oncology nurses and advanced practice
      clinicians are in a position to interpret research findings related to RT-induced
      diarrhea, enteritis, and colitis and to apply evidence-based practice principles
      in patients with cancer receiving RT to promote positive outcomes.

PMID- 20682503
TI  - A self-assessment tool for oncology nurses: preliminary implementation and
      evaluation.
AB  - Nurses who fail to identify knowledge gaps in their practice and who do not
      maintain competence place patients with cancer at risk for adverse events and
      poor outcomes. Self-assessment tools can assist oncology nurses in identifying
      knowledge deficits in fundamental oncology concepts. This article describes the
      development and implementation of a self-assessment tool to assist nurses in
      maintaining competence to provide safe, effective oncology care. The tool was
      developed after an examination of relevant literature, collaboration with an
      oncology team, and consideration of the Oncology Nursing Society's and American
      Nursing Association's standards of care. Preliminary evaluation suggests it may
      offer an effective means for oncology nurses to identify knowledge deficits and
      tailor educational interventions to address identified needs.

PMID- 20682504
TI  - Oral manifestations of cancer treatment in children: a review of the literature.
AB  - In Western countries, rising incidence and survival rates in childhood cancer
      have led to increased patient morbidity, including short- and long-term oral
      effects. Some acute oral complications occur three times more commonly in
      children than adults. This literature review sourced material from medical
      databases to discuss the acute and chronic oral complications of oncology
      treatment in children. The article explores caries, gingivitis, oral infections,
      and oral mucositis, as well as available tools for measuring their incidence,
      prevention, and treatment in children. Many tools and interventions appear to be
      available to prevent and treat oral complications of cancer treatment in
      children; however, they lack reliable and consistent research. Future research
      should use larger samples to report the incidence of oral complications, which
      would allow identification of children at increased risk. In addition, larger
      studies would provide baseline information to enable the construction of
      appropriate randomized clinical trials to test methods of prevention and proposed
      interventions for oral complications of cancer treatment in children.

PMID- 20682505
TI  - Management of patients with chronic lymphocytic leukemia treated with
      lenalidomide.
AB  - Lenalidomide is an immunomodulatory drug that has shown preliminary activity in
      the treatment of chronic lymphocytic leukemia (CLL). Much is known about the
      safety profile of lenalidomide from experience in other hematologic malignancies,
      such as myelodysplastic syndromes and multiple myeloma. In addition to the known
      adverse effects associated with lenalidomide (e.g., myelosuppression, rash,
      fatigue), some unique effects (e.g., tumor flare reactions, tumor lysis syndrome)
      have arisen during clinical studies of CLL. Typical signs of tumor flare
      reactions include early onset of painful enlargement of the lymph nodes or
      spleen, with or without low-grade fever, rash, and bone pain. Management may
      require nonsteroidal anti-inflammatory drugs or a short course of
      corticosteroids. Dose delays or reductions usually are not required for tumor
      flare reactions. Signs of tumor lysis syndrome may include shortness of breath,
      peripheral edema, generalized weakness, sweating, fever, and tachycardia.
      Untreated tumor lysis syndrome can result in renal impairment and congestive
      heart failure. Careful monitoring and appropriate management of treatment-related
      side effects can help ensure that patients with CLL achieve maximum therapeutic
      benefit from lenalidomide therapy.

PMID- 20682506
TI  - Use of neurokinin-1 receptor antagonists in patients receiving moderately or
      highly emetogenic chemotherapy.
AB  - Chemotherapy-induced nausea and vomiting (CINV) is a serious adverse effect of
      chemotherapy that limits patients' physical, mental, and functional capabilities
      and may cause a delay or cessation of treatment. Antiemetic therapy can reduce
      the incidence of CINV. Research, using data from visits by patients receiving
      moderately (MEC) or highly emetogenic chemotherapy (HEC), identified that
      antiemetics were prescribed for 86% (in 2007) and 82% (in 2008) of patients
      receiving MEC or HEC. For these visits, 5-hydroxytryptamine-3 receptor
      antagonists were prescribed in at least 97% of visits for both years, whereas
      neurokinin-1 (NK-1) receptor antagonists were prescribed at a rate of 10% and
      11%, respectively. Studies show that nurses and physicians underestimate the
      incidence of CINV after HEC and MEC. Oncology nurses often critically influence
      patients' selection of CINV therapy and can play a significant role in increasing
      awareness about the benefits of adding an NK-1 receptor antagonist to standard
      prophylactic regimens for acute and delayed CINV.

PMID- 20682507
TI  - Impact of treatment-related cardiac toxicity on lymphoma survivors: an
      institutional approach for risk reduction and management.
AB  - Despite improvements in treatment and overall survival rates, survivors of
      lymphoma may have long-term and late effects. Given the immense risk for cardiac
      disease after treatment for Hodgkin lymphoma and non-Hodgkin lymphoma, healthcare
      providers should focus on prevention of secondary adverse effects. The Dana
      Farber Cancer Institute has been working to develop guidelines to address the
      cardiotoxicities that impact the lymphoma survivor population.

PMID- 20682508
TI  - Assessing dyspnea in patients with non-small cell lung cancer in the acute care
      setting.
AB  - Dyspnea is a common and often overlooked symptom in patients with lung cancer.
      Oncology nurses are positioned to promptly assess, triage, and intervene to
      minimize dyspnea, but improved assessment is needed. As a result, this pilot
      study explores the validity and feasibility of two assessment scales on measuring
      the perception of dyspnea in patients with non-small cell lung cancer in the
      acute care setting.

PMID- 20682509
TI  - SPIKES: a framework for breaking bad news to patients with cancer.
AB  - SPIKES is an acronym for presenting distressing information in an organized
      manner to patients and families. The SPIKES protocol provides a step-wise
      framework for difficult discussions such as when cancer recurs or when palliative
      or hospice care is indicated. Each letter represents a phase in the six-step
      sequence. S stands for setting, P for perception, I for invitation or
      information, K for knowledge, E for empathy, and S for summarize or strategize.
      Breaking bad news is a complex communication task, but following the SPIKES
      protocol can help ease the distress felt by the patient who is receiving the news
      and the healthcare professional who is breaking the news. Key components of the
      SPIKES strategy include demonstrating empathy, acknowledging and validating the
      patient's feelings, exploring the patient's understanding and acceptance of the
      bad news, and providing information about possible interventions. Having a plan
      of action provides structure for this difficult discussion and helps support all
      involved.

PMID- 20682510
TI  - HIV: Just another chronic disease.

PMID- 20682511
TI  - Q: Can patients with COPD or asthma take a beta-blocker?

PMID- 20682512
TI  - Q: Do incretin drugs for type 2 diabetes increase the risk of acute pancreatitis?

PMID- 20682513
TI  - Painful red nodule on the right hand.

PMID- 20682514
TI  - Noninvasive tests for liver disease, fibrosis, and cirrhosis: Is liver biopsy
      obsolete?
AB  - Liver biopsy has been used to diagnose chronic liver disease and to assess the
      degree of hepatic inflammation and fibrosis. However, it is an invasive test with
      many possible complications and the potential for sampling error. Noninvasive
      tests are increasingly precise in identifying the cause of many cases of liver
      disease and even the amount of liver injury (fibrosis). This review discusses the
      role of noninvasive tests to diagnose liver disease and to assess hepatic
      fibrosis and cirrhosis.

PMID- 20682515
TI  - How to prevent glucocorticoid-induced osteoporosis.
AB  - When prescribing glucocorticoids for long-term treatment, physicians should take
      steps to prevent osteoporosis, a common and serious side effect of these drugs.

PMID- 20682516
TI  - A young woman with a breast mass: What every internist should know.

PMID- 20682518
TI  - Leukocytosis increases length of inpatient stay but not age-adjusted 30-day
      mortality, after hip fracture.

PMID- 20682517
TI  - Coronary heart disease in people infected with HIV.
AB  - People infected with human immunodeficiency virus (HIV) are living longer thanks
      to effective antiretroviral therapy. As this population ages, cardiovascular
      disease is becoming an important cause of morbidity and death. The authors of
      this review discuss the magnitude and likely mechanisms of the risk and
      strategies for managing it.

PMID- 20682519
TI  - Association between heme oxygenase-1 gene promoter polymorphisms and type 2
      diabetes mellitus: a HuGE review and meta-analysis.
AB  - Several studies have recently focused on the association between heme oxygenase-1
      (HMOX1) gene promoter polymorphisms and susceptibility to type 2 diabetes
      mellitus; however, results have been conflicting. This systematic Human Genome
      Epidemiology review and meta-analysis was undertaken to integrate previous
      findings and summarize the effect size of the association of HMOX1 gene promoter
      polymorphisms with susceptibility to type 2 diabetes. The authors retrieved all
      studies matched to search terms from the PubMed/MEDLINE, EMBASE, and ISI Web of
      Science databases that had been published through December 31, 2009. The articles
      were then checked independently by 2 investigators according to the eligibility
      and exclusion criteria. For all alleles and genotypes, odds ratios were pooled
      using either fixed-effects or random-effects models. An increased odds ratio for
      type 2 diabetes was observed in persons with the (GT)(n) L (long) allele as
      compared with those with the (GT)(n) S (short) allele (odds ratio = 1.12, 95%
      confidence interval: 1.02, 1.24; P = 0.02). Furthermore, the diabetes odds ratio
      for persons with the LL genotype, versus those with the SS genotype, was
      significantly increased (odds ratio = 1.25, 95% confidence interval: 1.04, 1.50;
      P = 0.02). Persons carrying longer (GT)(n) repeats in the HMOX1 gene promoter may
      have a higher risk of type 2 diabetes.

PMID- 20682520
TI  - Changes in weight at the end of life: characterizing weight loss by time to death
      in a cohort study of older men.
AB  - The purpose of this analysis was to characterize the natural history of weight
      change in the years prior to death among older persons and to examine how this
      pattern varies according to longevity and cause of death. Weight trajectories
      were analyzed by using data from 800 male decedents from the Baltimore
      Longitudinal Study of Aging (Maryland, 1958-2005) observed beginning an average
      of 19 years before death. A model including 3 distinct periods of weight change
      (weight stability/gain, mild weight loss, and accelerated weight loss before
      death) provided the best fit for all age-at-death groups. Approximately 9 years
      before death, the rate of weight loss increased to an average of 0.39 kg/year (P
      < 0.001) for all-cause mortality. For cancer deaths, weight loss accelerated
      significantly 3 years before death, regardless of age group. For cardiovascular
      deaths, the best-fitting inflection point increased with age, from 5 years for
      participants aged 60-69 years to 9-10 years before death for those aged 80 years
      or older. Results suggest that weight loss in older persons may begin earlier
      than previously believed. The duration of weight loss for noncancer deaths
      suggests that even distal changes in energy balance may be linked to risk of
      death.

PMID- 20682521
TI  - Plasma urate and Parkinson's disease in women.
AB  - Plasma urate has been consistently associated with a lower risk of Parkinson's
      disease in men, but it is less clear if this relation exists in women. Between
      1990 and 2004, the authors conducted a nested case-control study among
      participants of the female-only Nurses' Health Study. In controls (n = 504),
      plasma urate was positively associated with age, body mass index, alcohol
      consumption, hypertension, and use of diuretics and was inversely associated with
      physical activity and postmenopausal hormone use, as expected. Mean urate levels
      were 5.04 mg/dL for cases (n = 101) and 4.86 mg/dL for controls (P = 0.17). The
      age-, smoking-, and caffeine-adjusted rate ratio comparing women in the highest
      (>=5.8 mg/dL) with those in the lowest (<4.0 mg/dL) quartile was 1.33 (95%
      confidence interval: 0.69, 2.57; P(trend) = 0.4). Further adjustment for body
      mass index, physical activity, history of hypertension, and postmenopausal
      hormone use did not change the results. Unlike in men, these findings do not
      support the hypothesis that urate is strongly associated with lower rates of
      Parkinson's disease among women.

PMID- 20682522
TI  - Re: "Age dependence of the risk of intussusception following tetravalent rhesus
      human reassortant rotavirus tetravalent vaccine: is it beyond doubt?".

PMID- 20682523
TI  - "All that glitters...": evaluating interventions for emphysema.

PMID- 20682524
TI  - Home sleep testing: it is not about the test.

PMID- 20682525
TI  - Right-to-left shunts and saline contrast echocardiography.

PMID- 20682526
TI  - Bob Hope, pneumonia, and the counterfactual.

PMID- 20682528
TI  - Connective tissue disease-associated interstitial lung disease: a call for
      clarification.
AB  - This commentary highlights the present dilemmas surrounding the classification of
      a patient with interstitial pneumonia who has clinical features suggesting an
      associated connective tissue disease but the features fall short of a clear
      diagnosis of connective tissue disease-associated interstitial lung disease under
      the current rheumatologic classification systems. This commentary illustrates
      what we perceive to be the limitations in the present approach to the
      classification of this group of patients and discusses problems with redefining
      the diagnosis of undifferentiated connective tissue disease to encompass patients
      with interstitial pneumonia. Finally, we advocate not only for a
      multidisciplinary approach to evaluation, but also disease classification and
      offer a proposal to define them as a distinct phenotype--lung-dominant CTD--for
      which prognostic, therapeutic, and pathobiologic implications can be tested in
      future, hopefully multiinstitutional, studies.

PMID- 20682529
TI  - Lung volume reduction therapies for advanced emphysema: an update.
AB  - Observational and randomized studies provide convincing evidence that lung volume
      reduction surgery (LVRS) improves symptoms, lung function, exercise tolerance,
      and life span in well-defined subsets of patients with emphysema. Yet, in the
      face of an estimated 3 million patients with emphysema in the United States, < 15
      LVRS operations are performed monthly under the aegis of Medicare, in part
      because of misleading reporting in lay and medical publications suggesting that
      the operation is associated with prohibitive risks and offers minimal benefits.
      Thus, a treatment with proven potential for palliating and prolonging life may be
      underutilized. In an attempt to lower risks and cost, several bronchoscopic
      strategies (bronchoscopic emphysema treatment [BET]) to reduce lung volume have
      been introduced. The following three methods have been tested in some depth: (1)
      unidirectional valves that allow exit but bar entry of gas to collapse targeted
      hyperinflated portions of the lung and reduce overall volume; (2) biologic lung
      volume reduction (BioLVR) that involves intrabronchial administration of a
      biocompatible complex to collapse, inflame, scar, and shrink the targeted
      emphysematous lung; and (3) airway bypass tract (ABT) or creation of stented
      nonanatomic pathways between hyperinflated pulmonary parenchyma and bronchial
      tree to decompress and reduce the volume of oversized lung. The results of pilot
      and randomized pivotal clinical trials suggest that the bronchoscopic strategies
      are associated with lower mortality and morbidity but are also less efficient
      than LVRS. Most bronchoscopic approaches improve quality-of-life measures without
      supportive physiologic or exercise tolerance benefits. Although there is promise
      of limited therapeutic influence, the available information is not sufficient to
      recommend use of bronchoscopic strategies for treating emphysema.

PMID- 20682530
TI  - Multidetector CT scan findings of a right aberrant retroesophageal vertebral
      artery with an anomalous origin from a cervical aortic arch.
AB  - Various malformations of the aortic arch and great vessels have been reported in
      the literature, which reflects the complexity of their embryologic development.
      Most of them are of incidental finding and remain asymptomatic but can be
      responsible for respiratory or digestive symptoms and be associated with
      congenital cardiac diseases. We report the case of a patient presenting a right
      retroesophageal vertebral artery. This malformation was associated with multiple
      anomalies of the aortic arch. We report a classification of the most common
      aortic arch abnormalities by recalling Edwards double aortic arch model and
      embryologic variants. Here, we report on the rare case of a right retroesophageal
      vertebral artery. We assimilate this malformation to a vertebral arteria lusoria
      and attribute it to the lack of caudal migration of the fourth branchial arch,
      responsible for a left cervical aortic arch with an interruption between the
      right subclavian and vertebral arteries.

PMID- 20682531
TI  - Catheter entrapment in a pulmonary vein: a unique complication of pulmonary vein
      isolation.
AB  - Ablation strategies for the treatment of atrial fibrillation (AF) are associated
      with several potential complications. During electro-anatomic mapping of the left
      atrium (LA) before ablation, the ablation catheter was entrapped in the right
      inferior pulmonary vein (RIPV). After multiple unsuccessful gentle tractions,
      stronger maneuvers with rotation of the catheter slowly allowed its retrieval.
      Examination of the catheter showed a thin, translucent membrane covering its tip,
      suggesting complete stripping of a vein branch. Occlusion of the superior branch
      of the RIPV was confirmed by LA angiogram. During the following days, no
      pericardial effusion was noted, but the patient complained of light chest pain
      and mild hemoptysis, spontaneously resolving within 48 h. This case shows that
      catheter entrapment and mechanical disruption of a PV branch can be a rare
      potential complication of AF ablation. In this case, the outcome was
      spontaneously favorable and symptoms only included transient mild hemoptysis.

PMID- 20682532
TI  - Ground-glass centrilobular nodules on multidetector CT scan: incidental diagnosis
      in a patient with pneumonia.

PMID- 20682533
TI  - Sleep and hypertension.
AB  - Ambulatory BP studies indicate that even small increases in BP, particularly
      nighttime BP levels, are associated with significant increases in cardiovascular
      morbidity and mortality. Accordingly, sleep-related diseases that induce
      increases in BP would be anticipated to substantially affect cardiovascular risk.
      Both sleep deprivation and insomnia have been linked to increases in incidence
      and prevalence of hypertension. Likewise, sleep disruption attributable to
      restless legs syndrome increases the likelihood of having hypertension.
      Observational studies demonstrate a strong correlation between the severity of
      obstructive sleep apnea (OSA) and the risk and severity of hypertension, whereas
      prospective studies of patients with OSA demonstrate a positive relationship
      between OSA and risk of incident hypertension. Intervention trials with
      continuous positive airway pressure (CPAP) indicate a modest, but inconsistent
      effect on BP in patients with severe OSA and a greater likelihood of benefit in
      patients with most CPAP adherence. Additional prospective studies are needed to
      reconcile observational studies suggesting that OSA is a strong risk factor for
      hypertension with the modest antihypertensive effects of CPAP observed in
      intervention studies.

PMID- 20682534
TI  - A 65-year-old man with severe hyponatremia and alcohol abuse.

PMID- 20682535
TI  - A 31-year-old man with liver transplant and progressive jaundice.

PMID- 20682540
TI  - Extracorporeal membrane oxygenation support in management of severe respiratory
      failure secondary to 2009 influenza A(H1N1) virus.

PMID- 20682541
TI  - A real-time reverse transcriptase-polymer chain reaction to evaluate natural
      history of viral shedding in outpatient children and adolescents with pandemic
      2009 influenza A(H1N1).

PMID- 20682542
TI  - Comparison among different methods on measurement of total lung capacity in COPD.

PMID- 20682543
TI  - Quantifying latent TB infection: the dilemma continues.

PMID- 20682544
TI  - Increased morning cortisol level: effect of sleep fragmentation or stress
      response to the last annoying stimulus?

PMID- 20682545
TI  - Is pulmonary arterial hypertension really a late complication of systemic
      sclerosis?

PMID- 20682546
TI  - Effect of continuous positive airway pressure on inflammatory markers.

PMID- 20682547
TI  - Antigen-specific activation thresholds of CD8+ T cells are independent of IFN-I
      mediated partial lymphocyte activation.
AB  - Type-I IFN (IFN-I) are highly pleiotropic cytokines known to modulate immune
      responses and play an early central role in mediating antiviral defenses. We have
      shown that IFN-I mediate transient up-regulation of a distinct subset of
      lymphocyte surface activation markers on both B and T cells in vivo independent
      of cognate antigen: a state referred to as 'partial lymphocyte activation'. Here
      we investigated in vitro the possibility that partial lymphocyte activation may
      serve to lower the antigen-specific activation thresholds for T cells. We found
      that the kinetics of Ca(2+) flux in T cells responding to TCR cross-linking was
      not enhanced in partially activated T cells. Furthermore, following TCR
      stimulation with anti-cluster of differentiation (CD) 3 epsilon, a lower
      proportion of partially activated than naive T cells proliferated. In contrast,
      the proliferation of partially activated and naive ovalbumin peptide (OVAp,
      SIINFEKL) specific CD8(+) T cells (OT-I CD8(+) T cells) was similar when
      stimulated with OVAp. Surprisingly, using an enzyme-linked immunospot (ELISPOT)
      assay for IFN-gamma secretion, we found that a higher number of partially
      activated OT-I CD8(+) T cells expressed effector functions than did naive OT-I
      CD8(+) T cells. This is most readily explained by an increased survival of
      activated antigen-specific CD8(+) T cells from a pool of partially activated T
      cells than naive T cells. Overall, when examining the effects of early (Ca(2+)
      flux), intermediate (proliferation) or late events (IFN-gamma secretion) of T
      cell activation, we found that partial activation promotes the survival but does
      not alter the antigen-specific activation thresholds of CD8(+) T cells.

PMID- 20682548
TI  - Randomized phase III trial of 2nd line gemcitabine and paclitaxel chemotherapy in
      patients with advanced bladder cancer: short-term versus prolonged treatment
      [German Association of Urological Oncology (AUO) trial AB 20/99].
AB  - BACKGROUND: The second-line chemotherapeutic treatment for metastatic urothelial
      cancer (UC) after failure of cisplatin-based first-line therapy needs to be
      improved. Based on encouraging phase II data of gemcitabine and paclitaxel
      (Taxol) (GP), this trial was designed to compare a short-term (arm A) versus a
      prolonged (arm B) second-line combination chemotherapy of GP. PATIENTS AND
      METHODS: Of 102 randomized patients, 96 were eligible for analysis. Primary end
      point was overall survival (OS). Secondary end points were progression-free
      survival (PFS), objective response rates (ORR) and toxicity. RESULTS: Neither OS
      [arm A: 7.8 (95% CI: 4.2-11.4), arm B: 8.0 (95% CI: 4.9-11.1) months] and PFS
      [arm A: 4.0 (95% CI: 0-8.0), arm B: 3.1 (95% CI: 1.9-4.2) months] nor ORR (arm A:
      37.5%, arm B: 41.5%) were significantly different. On prolonged treatment, more
      patients experienced severe anemia (arm A: 6.7% versus arm B: 26.7% grade III/IV
      anemia; P = 0.011). In six patients, treatment was stopped during the first cycle
      due to disease progression or toxicity. Two patients died due to treatment
      related toxic effects. CONCLUSION: Due to rapid tumor progression and toxicity at
      this dosage and schedule in a multicenter setting, it was not feasible to deliver
      a prolonged regimen. However, a high response rate of ~40% makes GP a promising
      second-line treatment option for patients with metastatic UC.

PMID- 20682549
TI  - Breast cancer incidence and time trend in France from 1990 to 2007: a population
      based study from two French cancer registries.
AB  - BACKGROUND: The hypothesis of a link between breast cancer and hormone
      replacement therapy (HRT) is evoked to explain the recent decrease of incidence
      observed in several countries. The purpose of our study is to analyse the
      evolution of breast cancer incidence by stage. MATERIALS AND METHODS: We used
      data from Tarn and Isere French cancer registries for the period 1990-2007.
      Trends of annual world population standardised incidence rates were studied using
      the Joinpoint method. RESULTS: From 1990 to 1999, the incidence of invasive
      breast cancer increased annually by 1.2%, then by 4.8% from 1999 till 2003 and
      then decreased by 1.7%. For the women aged 50-74 years, annual changes were,
      respectively, 1.5%, 6.0% and 3.4%. In this group, the incidence of T1/T2-N0-M0
      stages increased annually by 4.6% until 2003 and then decreased by 2.2%. Since
      1990, the incidence of in situ breast cancer increased annually by 5%. From 2003
      to 2004, prescribing of HRT decreased substantially. CONCLUSIONS: : Since 2003,
      the incidence of invasive breast cancer decreased for women aged 50-74 years,
      mainly involving T1/T2-N0-M0 stages. The reduction in HRT prescription may partly
      explain this decrease. The incidence of in situ breast cancer didn't decrease
      during the whole period.

PMID- 20682550
TI  - Immunoglobulin D multiple myeloma: response to therapy, survival, and prognostic
      factors in 75 patients.
AB  - BACKGROUND: To analyze the clinical features, outcomes including efficacy of
      treatment, and prognostic factors of patients with immunoglobulin D multiple
      myeloma (IgD MM). DESIGN AND METHODS: Seventy-five patients diagnosed with IgD MM
      were selected from the Korean Myeloma Registry database (www.myeloma.or.kr).
      RESULTS: Median age was 57 years and the main presenting features were bone pain
      (77%). Renal function impairment and hypercalcemia were present in 40 (53%) and
      20 (27%) patients. Sixty-seven patients (89%) had lambda light chains. Forty
      eight patients (64%) were of stage III by International Staging System. Twenty
      six patients (53%) had chromosomal abnormalities mostly by conventional
      cytogenetics. Thirty-nine patients (54%) were treated with vincristine,
      adriamycin, and dexamethasone chemotherapy; the overall response rate (ORR) of
      56%. Sixteen patients (22%) received first-line chemotherapy including new drugs
      (bortezomib or thalidomide), with an ORR of 81%. At a median follow-up time of
      28.6 months, median overall survival (OS) was 18.5 months. Age, extramedullary
      plasmacytoma, del(13) or hypoploidy, serum beta(2) microglobulin level, and
      platelet count were significant prognostic factors for OS. CONCLUSIONS: IgD MM is
      an aggressive disease that is usually detected at an advanced stage. Despite a
      positive initial response, survival after relapse was dismal. Intensive treatment
      strategies before and following stem cell transplantation may improve outcomes in
      younger patients.

PMID- 20682551
TI  - What is the time course of reversal of tachycardia-induced cardiomyopathy?

PMID- 20682552
TI  - Pulmonary vein isolation with the 30 and 35 mm high-density mesh ablator.
AB  - AIMS: To analyse procedural results and clinical outcome of paroxysmal atrial
      fibrillation (AF) ablation using the 30 and 35 mm high-density mesh ablator
      (HDMA, Bard Electrophysiology). METHODS AND RESULTS: Sixty-four consecutive
      patients were ablated with the HDMA catheter (26 with the 30 mm, 38 with the 35
      mm device). If pulmonary vein (PV) isolation was unsuccessful, ablation was
      continued using a conventional 4 mm ablation catheter. Success was defined as
      freedom of AF at 6 months after a single procedure without antiarrhythmic drugs.
      PV isolation could be obtained in 84/106 (79%) PVs in the 30 mm group vs. 149/153
      (97%) PVs in the 35 mm group (P < 0.001). All non-isolated veins were
      successfully isolated with the conventional 4 mm ablation catheter. Freedom of AF
      at 6 months was 19% in the 30 mm group vs. 18% in the 35 mm group (P = NS).
      During a repeat procedure in 19 patients, 69% of the PVs were reconnected with an
      incremental LA-PV delay of 11 +/- 15 ms compared with baseline. CONCLUSION: (i)
      Compared with the 30 mm, the 35 mm HDMA catheter proves to be more efficient in
      obtaining acute pulmonary vein isolation, (ii) despite these promising procedural
      results, the clinical outcome is disappointing and (iii) the high reconnection
      rate and the limited delay in PV potentials suggest that PV isolation with the
      HDMA catheter is not permanent.

PMID- 20682554
TI  - Atrial undersensing in VDD pacing: should we blame calcium-channel blockers?

PMID- 20682553
TI  - Transoesophageal echocardiography predictors of periprocedural cerebrovascular
      accident in patients undergoing catheter ablation of atrial fibrillation.
AB  - AIMS: To assess the utility of transoesophageal echocardiography (TEE) parameters
      such as spontaneous echo contrast (SEC), left atrial (LA) appendage velocities,
      and aortic plaque in predicting periprocedural cerebrovascular accidents (CVAs)
      in patients undergoing catheter ablation of atrial fibrillation (AF). METHODS AND
      RESULTS: Five hundred and seventy-nine consecutive patients underwent catheter
      ablation of AF with pre-procedural TEE, 94% of whom also received pre-procedural
      warfarin and enoxaparin bridging. Of the 579 patients, 10 patients (cases) who
      developed periprocedural CVA (1.7%) and 40 randomly selected patients who did not
      develop CVA (controls) were included (50 study patients, age 58 +/- 11 years, 82%
      male, 54% persistent AF). Periprocedural CVA was defined as a new neurological
      deficit that occurred anytime between the start of the procedure and 30 days
      after AF ablation. Demographic, clinical, and TEE variables of cases and controls
      were compared using standard statistical analyses. Patients with CVA more often
      had coronary artery disease [odds ratio (OR) 6.0, P = 0.03], previous history of
      CVA (OR 8.2, P = 0.02), and CHADS(2) score >= 2 (OR 5.4, P = 0.03) than patients
      without CVA. There was no difference in any of the TEE parameters (SEC, LA
      appendage velocity and area, patent foramen ovale, atrial septal aneurysm, valve
      abnormality, and aortic plaque). When these TEE parameters were adjusted for
      coronary artery disease, prior CVA and CHADS(2) >= 2, none emerged as an
      independent predictor of CVA. CONCLUSION: Transoesophageal echocardiographic
      variables (other than LA thrombus) were not associated with the occurrence of
      periprocedural CVA in our patients undergoing catheter ablation of AF who
      generally received pre-procedural anticoagulation. Despite serving as markers of
      a thrombogenic milieu, the presence of SEC, low LA appendage velocities, and
      aortic plaque may not increase the risk of periprocedural CVA after AF ablation.

PMID- 20682555
TI  - A case for ambidextrous doctors.
AB  - We report the case of a 30-year-old man with situs inversus totalis, recurrent
      orthodromic reciprocal tachycardia, and the Wolff-Parkinson-White syndrome. He
      underwent, in our department, radiofrequency ablation of an accessory pathway
      (AP) located in the lateral mitral atrioventricular ring. Ablation of the AP was
      carried out successfully through a patent foramen ovale under fluoroscopic
      guidance, in a right anterior oblique projection with a 30 degrees  tilt and in
      anteroposterior views. We also used a mirror reversal of electrocardiogram (ECG)
      leads to better judge the site of the AP by using existing ECG algorithms.
      Complete situs inversus is a rare disorder, which has no consequence for the
      patient in the absence of cardiac or extracardiac involvement. Ablation of APs in
      situs inversus has been previously reported in only three cases of complete situs
      inversus and one case of situs ambiguous. In patients with mirror-image
      dextrocardia, APs seem more often located on the 'left' free wall (mitral
      annulus), as in the normal population. Radiofrequency ablation is feasible and
      safe after mirror reversion of the ECG electrodes and fluoroscopy.

PMID- 20682556
TI  - Role of constitutively active acetylcholine-mediated potassium current in atrial
      contractile dysfunction caused by atrial tachycardia remodelling.
AB  - AIMS: Atrial fibrillation (AF)-induced contractile dysfunction contributes
      importantly to thrombo-embolic stroke, the most serious AF complication. Atrial
      cardiomyocytes have a constitutively active acetylcholine-regulated K(+)-current
      (I(KAChc)) that is enhanced by atrial tachycardia (AT). I(KAChc) contributes to
      action potential duration (APD) shortening in AT-remodelled atrial
      cardiomyocytes; APD regulates contractility by controlling Ca(2+)-loading and
      systolic Ca(2+)-release. This study investigated the potential role of I(KAChc)
      in AF-related contractile dysfunction. METHODS AND RESULTS: Dogs were divided
      into two groups: (i) unpaced control (CTL); (ii) AT (400 bpm for at least 7
      days). Tertiapin-Q (TQ), a selective I(KAChc) blocker, was used to define
      I(KAChc) contributions to contractility. Single-cell left atrial (LA)
      intracellular Ca(2+)-transients (CaTrs), cell-shortening (CS), and whole LA
      tissue tension-generation were measured. Atrial tachycardia increased I(KAChc).
      Whole LA contractility was decreased in AT (0.17 +/- 0.05 g) compared with CTL
      (0.40 +/- 0.09 g), with significant reversal (0.30 +/- 0.06 g) after TQ
      administration. Ca(2+)-transient amplitude and CS in single-cell were decreased
      by AT compared with CTL (167 +/- 14 vs. 88 +/- 10 nM; 10.3 +/- 1.3 vs. 1.7 +/-
      0.3 um, respectively; P < 0.001). The AT-induced reductions in single-cell CaTr
      amplitude and CS were partly reversed by TQ administration (88 +/- 10 vs. 112 +/-
      16 nM; P < 0.001; 1.7 +/- 0.3 vs. 3.6 +/- 0.7 um; P < 0.01). We then measured
      CaTr and CS with carbachol and/or TQ to vary I(KACh) at various extracellular
      [Ca(2+)]. The CaTr-CS relationship was linear and AT results fell on the
      regression line, indicating that AT-remodelling effects on contractility are
      attributable to reduced CaTr. CONCLUSION: Up-regulated I(KAChc) contributes to AF
      related contractile dysfunction and could be a novel target to prevent
      hypocontractility-related thrombo-embolic complications.

PMID- 20682557
TI  - Impact of angiotensin-converting enzyme-inhibitors and angiotensin receptor
      blockers on long-term outcome of catheter ablation for atrial fibrillation.
AB  - AIMS: We hypothesized that modulation of the renin-angiotensin-aldosterone system
      (RAAS) improves success following catheter ablation for atrial fibrillation (AF).
      METHODS AND RESULTS: We examined a prospective registry of consecutive patients
      undergoing catheter ablation of paroxysmal or persistent AF between November 2004
      and December 2008. Patients were divided based on whether they were taking RAAS
      modulators at the time of their first procedure and examined on an intention to
      treat basis. There were 419 patients (222 paroxysmal and 197 persistent AF) who
      underwent 1.8 +/- 0.9 procedures. Median follow-up from the last procedure was
      1.7 (range 0.9-5.0) years. There were 142 patients on RAAS modulators; they were
      older, more likely to suffer from hypertension, diabetes, coronary disease, or
      left ventricular impairment. Overall, sinus rhythm was maintained in 73.2% of
      those taking RAAS modulators vs. 77.6% of those taking none (P = 0.304).
      Multivariate analysis showed no impact of RAAS modulators [hazard ratios (HR):
      1.97, CI: 0.56-6.89, P = 0.290] but also no effect of hypertension, ischaemic
      heart disease, left ventricular impairment, or diabetes that should have
      confounded results (persistent AF was found to predict failure; HR: 0.34, CI:
      0.14-0.84, P = 0.020). Subgroup analysis of patients with risk factors for
      developing AF (hypertension, coronary artery disease, left ventricular
      impairment, or diabetes) found no benefit in this context, with sinus rhythm
      maintained in 73.2% of those taking RAAS modulators compared with 69.9% of those
      taking none (P = 0.574). CONCLUSION: Modulation of the RAAS does not appear to
      affect maintenance of sinus rhythm following catheter ablation of AF.

PMID- 20682558
TI  - Focal ventricular arrhythmias originating from the left ventricle adjacent to the
      membranous septum.
AB  - AIMS: We report the features of focal ventricular arrhythmias (VAs) arising from
      the left ventricle (LV) adjacent to the membranous septum. METHODS AND RESULTS:
      We studied eight patients (five men, 65 +/- 10 years) with (n = 2) or without
      structural heart disease (n = 6) who had ventricular tachycardia (n = 4) or
      premature ventricular contractions (n = 4) originating from the LV septum
      underneath the aorta. Ventricular arrhythmias exhibited a focal activation
      pattern, left (n = 4) or right bundle branch block (n = 4), respectively, left
      superior (n = 4) or inferior axis QRS morphology (n = 4), negative QRS polarity
      in lead III and early or no precordial transition in all. During all of these
      VAs, far-field electrograms in the His bundle (HB) region preceded the QRS onset.
      In all patients, ventricular pre-potentials were recorded during VAs while late
      potentials were recorded in sinus rhythm at the border of a localized low-voltage
      area underneath the aorta. Radiofrequency catheter ablation at the presumed sites
      of origin successfully eliminated VAs in five patients and was abandoned in the
      remaining three because the HB electrogram was recorded at that site. CONCLUSION:
      Focal VAs may arise from the LV adjacent to the membranous septum as a part of
      the LV ostium, and broadens the spectrum of LV ostium VAs.

PMID- 20682559
TI  - Microarray-based STR genotyping using RecA-mediated ligation.
AB  - We describe a novel assay capable of accurately determining the length of short
      tandem repeat (STR) alleles. STR genotyping is achieved utilizing RecA-mediated
      ligation (RML), which combines the high fidelity of RecA-mediated homology
      searching with allele-specific ligation. RecA catalyzes the pairing of synthetic
      oligonucleotides with one strand of a double-stranded DNA target, in this case a
      PCR amplicon. Ligation occurs only when two adjacent oligonucleotides are base
      paired to the STR region without any overlap or gap. RecA activity is required to
      overcome the inherent difficulty of annealing repeated sequences in register.
      This assay is capable of determining STR genotypes of human samples, is easily
      adapted to high throughput or automated systems and can have widespread utility
      in diagnostic and forensic applications.

PMID- 20682561
TI  - Early predictors of the long-term outcome of low back pain--results of a 22-year
      prospective cohort study.
AB  - BACKGROUND: poor outcome of low back pain in patients seen in general practice is
      related to the pain history, physical impairment and working conditions, at least
      in short-term follow-ups. We do not know if these findings hold, seen from the
      perspective of decades. OBJECTIVES: to show if patients consulting the GP for the
      first time regarding an episode of low back pain have excess poor outcome 22
      years later and, if so, whether the best predictors are data based on the
      symptoms, clinical signs or work history. The design of the study is a 22-year
      follow-up of an inception cohort of 78 patients with low back pain. The setting
      of the study is a single general practice in a suburb of Copenhagen, Denmark.
      METHODS: selected predictors were separated into pain characteristics, clinical
      signs and indicators related to the work history. Outcome measures were the 1
      year period prevalence of low back pain, use of painkillers for low back pain,
      use of health care providers, impairments due to low back pain and unfitness for
      work caused by low back pain. The influence of the predictors was assessed by
      relative risks. RESULTS: after 22 years, four out of five patients still
      experienced low back pain. The perception of poor working conditions correlates
      with recurrent low back pain, intake of painkillers and limitations to daily
      life. CONCLUSION: compared with pain history and clinical findings, the
      perception of workload is a better predictor of the long-term outcome of low back
      pain.

PMID- 20682560
TI  - A practical, bioinformatic workflow system for large data sets generated by next
      generation sequencing.
AB  - Transcriptomics (at the level of single cells, tissues and/or whole organisms)
      underpins many fields of biomedical science, from understanding the basic
      cellular function in model organisms, to the elucidation of the biological events
      that govern the development and progression of human diseases, and the
      exploration of the mechanisms of survival, drug-resistance and virulence of
      pathogens. Next-generation sequencing (NGS) technologies are contributing to a
      massive expansion of transcriptomics in all fields and are reducing the cost,
      time and performance barriers presented by conventional approaches. However,
      bioinformatic tools for the analysis of the sequence data sets produced by these
      technologies can be daunting to researchers with limited or no expertise in
      bioinformatics. Here, we constructed a semi-automated, bioinformatic workflow
      system, and critically evaluated it for the analysis and annotation of large
      scale sequence data sets generated by NGS. We demonstrated its utility for the
      exploration of differences in the transcriptomes among various stages and both
      sexes of an economically important parasitic worm (Oesophagostomum dentatum) as
      well as the prediction and prioritization of essential molecules (including
      GTPases, protein kinases and phosphatases) as novel drug target candidates. This
      workflow system provides a practical tool for the assembly, annotation and
      analysis of NGS data sets, also to researchers with a limited bioinformatic
      expertise. The custom-written Perl, Python and Unix shell computer scripts used
      can be readily modified or adapted to suit many different applications. This
      system is now utilized routinely for the analysis of data sets from pathogens of
      major socio-economic importance and can, in principle, be applied to
      transcriptomics data sets from any organism.

PMID- 20682562
TI  - Discrepancies between the self-reporting of STI preventive care and the actual
      care provided by male doctors to male patients in Karnataka, India.
AB  - OBJECTIVE: To examine the discrepancies between the self-reporting of STI
      preventive care and the actual care provided by male doctors to male patients in
      several subdistricts of the state of Karnataka, south India. METHODS: Of 3376
      allopathic medical practitioners (doctors) enumerated, 2846 were contacted in
      person. Doctors who saw at least five patients with STI a month were then
      interviewed (814). Further, 451 of these practitioners were visited by a
      'surrogate patient.' Comparative analyses were conducted of items from the survey
      questionnaire and from the surrogate patient answer sheet that unambiguously
      tapped into the same information. RESULTS: Systematic differences in the self
      report by the doctors and the report by the surrogate patients were found. For
      instance, 99% of practitioners reported examining the patients, whereas only 71%
      of surrogate patients reported being examined. 96% of practitioners reported
      advising condom use, whereas only 19% of surrogate patients reported receiving
      this advice. 97% of practitioners reported advising partner treatment, whereas
      only 10% of surrogate patients reported receiving this advice. Younger
      practitioners, doctors in rural centres and doctors with STI in-service training
      were more likely to be discordant in what they self-reported and what surrogate
      patients reported. CONCLUSIONS: The discrepancies between doctor self-reporting
      and surrogate patient observations bring into question the reliability of
      practitioner recall, suggesting that the use of self-reporting surveys should be
      reassessed.

PMID- 20682563
TI  - Septic bilateral pulmonary candidiasis successfully treated with anidulafungin
      therapy in two patients with peritoneal carcinomatosis.

PMID- 20682564
TI  - European clinical isolate of Proteus mirabilis harbouring the Salmonella genomic
      island 1 variant SGI1-O.

PMID- 20682565
TI  - Antibiotic susceptibility of unselected uropathogenic Escherichia coli from
      female Dutch general practice patients: a comparison of two surveys with a 5 year
      interval.
AB  - OBJECTIVES: To optimize empirical treatment of urinary tract infections (UTIs),
      regular evaluation of the antibiotic susceptibility of the most common
      uropathogen, Escherichia coli, is necessary. We compared the antibiotic
      prescription rate for UTIs in women and the E. coli antibiotic susceptibility
      results, including the prevalence of extended-spectrum beta-lactamase (ESBL)
      producing strains, in 2009 with data collected 5 years earlier. PATIENTS AND
      METHODS: Urinary samples from female patients with symptoms of uncomplicated UTI
      in 42 general practices were collected over a 6 month period. Uropathogens were
      identified and the antibiotic susceptibility of E. coli was determined. RESULTS:
      We analysed 970 urine cultures, of which 785 (81%) were considered positive (>=
      10(3) cfu/mL). E. coli accounted for 72% of the isolates. ESBLs showed an
      increase between the two surveys (0.1% versus 1%; P < 0.001), while no difference
      in antibiotic susceptibility to the commonly used antimicrobial agents for UTIs
      was observed. A significantly lower susceptibility rate to co-amoxiclav was
      observed in the eastern region of the Netherlands, as compared with the northern
      region (80% versus 92%; P <  0.05). Consistent with national guidelines, the
      prescription rate of trimethoprim decreased over time (19% versus 5%; P  < 0.05)
      whereas nitrofurantoin and fosfomycin rates showed an increase (58% versus 66%
      and 0% versus 6% respectively, both P  < 0.05). CONCLUSIONS: Over a 5 year
      period, the antibiotic susceptibility of uropathogenic E. coli did not change in
      female patients with uncomplicated UTI in the Netherlands, but ESBL prevalence
      increased. With respect to the prescription of antimicrobial agents, compliance
      with national UTI guidelines was good.

PMID- 20682566
TI  - Analyses of teicoplanin concentrations from 1994 to 2006 from a UK assay service.
AB  - Objectives An analysis of the trough serum concentrations sent to the UK
      Antimicrobial Reference Laboratory for teicoplanin therapeutic drug monitoring
      (TDM). Methods All trough concentrations over a 13 year period were analysed and
      the percentages were calculated for the following: <10 mg/L (a sub-optimal
      concentration for all); >=10-<20 mg/L (the target used for ordinary Gram-positive
      infections); >=20-<60 mg/L (the target for all severe staphylococcal infections
      including endocarditis); and >=60 mg/L (the concentration associated with
      toxicity). Results The percentage of patients with concentrations of <10 mg/L
      decreased each year to 13% in 2006. Almost 40% of the samples each year were in
      the >=10-<20 mg/L range. In 1996, the percentage of samples in the >=20-<60 mg/L
      range reached a study high of ~70%. That percentage then fell to 30% and
      increased slowly to 50% at the end of the study. Fewer than 5% of the samples
      were >=60 mg/L. Conclusions Our study shows that there is a need to increase the
      initial dose or extend the number of days that the loading dose is used in a
      significant number of patients. With such a wide optimal range and a low
      potential for toxicity, it is unclear why optimal therapy is not achieved in a
      higher percentage of patients.

PMID- 20682567
TI  - Prevention of postdural puncture headache after accidental dural puncture: a
      quantitative systematic review.
AB  - No clear consensus exists on how to best prevent severe headache from occurring
      after accidental dural puncture. We conducted a quantitative systematic review to
      identify all available evidence for the prevention of postdural puncture headache
      (PDPH) and included 17 studies with 1264 patients investigating prophylactic
      epidural blood patch (PEBP), epidural morphine, intrathecal catheters, and
      epidural or intrathecal saline. The relative risk (RR) for headache after PEBP
      was 0.48 [95% confidence interval (CI): 0.23-0.99] in five non-randomized
      controlled trials (non-RCTs) and 0.32 (0.10-1.03) in four randomized controlled
      trials (RCTs). The RR for epidural morphine (based on a single RCT) was 0.25
      (0.08-0.78). All other interventions were based on non-RCTs and failed
      statistical significance, including long-term intrathecal catheters with an RR of
      0.21 (0.02-2.65). There are a number of promising options to prevent PDPH, yet
      heterogeneity between the studies and publication bias towards small non-RCTs
      with positive results limits the available evidence. Thus, a large multicentre
      RCT is needed to determine the best preventative practices.

PMID- 20682568
TI  - Electrocardiographic changes during continuous intravenous application of
      bupivacaine in neonatal pigs.
AB  - BACKGROUND: It is controversial as to whether T-wave elevation is caused by local
      anaesthetics, epinephrine, or their combination. It has been shown that T
      elevation after intravascular injection of a small bupivacaine test dose is
      caused by epinephrine and not by bupivacaine. The aim of this study was to
      investigate ECG changes with higher doses of i.v. bupivacaine. METHODS: Thirty
      neonatal pigs were anaesthetized with sevoflurane and their tracheas intubated
      and artificially ventilated. Under steady-state conditions, bupivacaine was
      continuously infused (flow rate 3.2 ml kg(-1) min(-1)) by a syringe infusion pump
      through a central venous catheter. Group 1 received bupivacaine 0.125%, Group 2
      bupivacaine 0.5%. The ECG was continuously printed and subsequently analysed for
      alterations in heart rate, ventricular de- and repolarization, and arrhythmias at
      1.25, 2.5, and 5 mg kg(-1) bupivacaine infused. RESULTS: Sinus rhythm persisted
      in all pigs. Heart rate decreased progressively in both groups, but this was
      significantly more pronounced in Group 1. T-wave elevation occurred in 40% and 0%
      (Groups 1 and 2) at 1.25 mg kg(-1), in 80% and 0% at 2.5 mg kg(-1), and in 93%
      and 80% at 5 mg kg(-1) bupivacaine infused. There were significant differences
      between the two groups at 1.25 and 2.5 mg kg(-1) infused. CONCLUSIONS: Higher
      doses of i.v. infused bupivacaine can cause T-elevation. With slower injection
      technique, T-elevation can already be detected at lower bupivacaine doses
      administered.

PMID- 20682569
TI  - Xylometazoline pretreatment reduces nasotracheal intubation-related epistaxis in
      paediatric dental surgery.
AB  - BACKGROUND: Epistaxis is the most common complication encountered during
      nasotracheal intubation (NTI) in children. The aim of this study was to test the
      efficacy of prophylactic intranasal admixture of xylometazoline and local
      anaesthetic gel in reducing epistaxis after NTI in children. METHODS: Children
      presenting for dental procedures requiring NTI were randomly allocated into two
      groups: Group 1 (xylometazoline group, n=53) and Group 2 (control group, n=51).
      After sevoflurane inhalation induction, the more patent nostril in each subject
      was lubricated with lidocaine 2% (1 ml) jelly, followed by 0.6 ml of either
      xylometazoline hydrochloride 0.1% nasal drops (Group 1) or sodium chloride 0.9%
      (Group 2). The presence and extent of bleeding occurring during intubation,
      extubation, or both and navigability through the nasal passage were assessed.
      RESULTS: The incidence and severity of bleeding were significantly reduced
      between the study group (7.5%) compared with the control group (27.5%; P<0.01).
      Navigability was similar in both groups. CONCLUSIONS: Admixture of intranasal
      xylometazoline 0.1% drops and lidocaine 2% jelly reduced the incidence and
      severity of epistaxis after NTI in preschool children.

PMID- 20682570
TI  - Feedback system to estimate the quality of outpatient preoperative evaluation
      records: an analysis of end-user satisfaction.
AB  - BACKGROUND: During preanaesthesia evaluation at an outpatient clinic, information
      is summarized and structured. We aimed to estimate the effectiveness of this
      process by determining the proportion of patients presenting for surgery who had
      valid preoperative anaesthesia assessment records, and also the proportion of
      patients with a record that contained sufficient information. METHODS: This study
      included all non-cardiac surgery procedures performed in adults in 2006 and 2007
      in a university hospital. In each case, we asked the anaesthesiologist actually
      providing anaesthesia to assess the quality of the preoperative record on an
      electronic feedback form showing a predefined drop down menu and a free text box.
      The primary outcome was the proportion of procedures with a valid record (< 6
      months old) that also contained sufficient and adequate information to safely
      provide anaesthesia. Secondly, all predefined remarks were assessed for relevance
      and the proportion of (relevant) remarks per individual anaesthesiologist was
      calculated. RESULTS: During the study period, 21 454 procedures were performed. A
      valid record was available in 20 700 procedures (97%). In 459 (2%) cases, a
      remark (mostly about not detected comorbidity) was given by the anaesthesia
      provider, of which 347 (76%) were assessed as 'relevant', resulting in 20 353
      (95%) valid records containing sufficient and adequate information. Between
      individual anaesthesiologists, the percentage remarks ranged from 0.4% to 12.7%.
      CONCLUSIONS: On entering the operating theatre, 95% of elective surgery patients
      had a preanaesthesia evaluation record that contained sufficient and adequate
      information to safely provide anaesthesia. There was large variability in
      reporting remarks.

PMID- 20682571
TI  - Effect of tracheal tube cuff shape on fluid leakage across the cuff: an in vitro
      study.
AB  - BACKGROUND: This study compared the fluid leakage in the new 'tapered' shaped
      against the classic 'cylindrical' shaped tracheal tube cuffs when placed in
      different sized tracheas. METHODS: The 7.5 mm internal diameter (ID) tracheal
      tube cuffs-Tapered Seal Guard (TSG), Standard Seal Guard (SSG), Hi-Lo, Microcuff,
      Ruesch, and Portex Profile-were compared in an in vitro apparatus. Vertical
      artificial tracheas with 16, 20, and 22 mm ID were intubated, 5 ml clear water
      was applied above the unlubricated tube cuffs, and fluid leakage was measured up
      to 60 min. Data of tapered vs non-tapered tube cuffs (16 observations) were
      compared for each tracheal diameter using the Mann-Whitney test. RESULTS: Median
      (range) fluid leakage (ml) at 60 min was 2.14 (0.05-4.88), 1.14 (0.00-4.84), and
      0.13 (0.00-1.32), respectively, for 16, 20, and 22 mm tracheas in the TSG tube
      studies when compared with 4.58 (0.44-4.88), 2.21 (0.00-4.81), and 0.00 (0.00
      4.81) in the SSG tube and 4.54 (1.54-4.82), 0.90 (0.00-4.49), and 4.85 (4.40
      4.99) in the Microcuff tube studies. Leakage in all polyvinylchloride (PVC) tube
      cuffs was almost complete (5 ml) within 5 min (P<0.001). CONCLUSIONS: The tapered
      PU tube cuff was as effective as the cylindrical PU cuffs in smaller tracheal
      diameters and was more efficient than the cylindrical Microcuff PU tube cuff in
      larger tracheal diameter in preventing subglottic fluid leakage across the tube
      cuff tested in this in vitro study. PVC tube cuffs leaked much more and faster
      than PU cuffs.

PMID- 20682572
TI  - Evaluation of the surgical stress index during spinal and general anaesthesia.
AB  - BACKGROUND: Although in modern anaesthesia, monitoring depth of anaesthesia and
      quality of neuromuscular block are routine, monitoring of analgesia still remains
      challenging. Recently, the surgical stress index (SSI), derived from finger
      photoplethysmographic signal, was introduced as a surrogate variable reflecting
      the nociception-antinociception balance. This study aimed at evaluating the SSI
      in patients undergoing regional anaesthesia either alone or combined with
      sedation compared with patients undergoing general anaesthesia (GA). METHODS:
      Seventy-one patients undergoing general (n=24) or spinal anaesthesia with (n=24)
      or without sedation (n=23) were included. SSI was measured the day before surgery
      and at defined time points during anaesthesia and surgery and also in the
      recovery room. SSI was compared with haemodynamic variables like heart rate and
      systolic arterial pressure. RESULTS: The SSI was higher in patients undergoing
      spinal anaesthesia [mean 65, CI (59.3-70.5)] compared with GA [48 (39.9-56.4),
      P<0.01], and baseline [41 (37.3-44.2), P<0.001]. During spinal anaesthesia with
      sedation [44 (36.2-50.9)], it was comparable with the baseline level (P>0.05). In
      comparison with baseline, SSI in the recovery room was higher in patients after
      GA [59 (48.4-67.9), P<0.025] but not after spinal anaesthesia [53 (47.6-60.1),
      P>0.05] or after spinal anaesthesia with sedation [54 (45.8-65.1), P>0.05].
      Changes of the SSI were not reflected by changes of haemodynamic variables.
      CONCLUSIONS: In fully awake patients under spinal anaesthesia, the SSI does not
      reflect the nociception-antinociception balance. This may be due to the influence
      of mental stress on the sympathetic nervous system. Even light sedation
      attenuates these influences.

PMID- 20682573
TI  - Vapocoolant spray vs subcutaneous lidocaine injection for reducing the pain of
      intravenous cannulation: a randomized, controlled, clinical trial.
AB  - BACKGROUND: We compared the efficacy, acceptability, and safety of a topical
      vapocoolant alkane spray and 1% plain s.c. lidocaine in reducing pain from i.v.
      cannulation. METHODS: This was a non-blinded, randomized, controlled trial, in a
      large emergency department. Adult patients requiring i.v. cannulation were
      enrolled. The vapocoolant was administered from a pressure pack, at a distance of
      12 cm for 2 s, and cannulation was undertaken within 15 s. Alternatively, 1%
      plain lidocaine 0.2 ml was administered s.c. using a 27 G needle, and cannulation
      was undertaken after a minimum of 30 s. The primary outcomes were anaesthetic
      administration and cannulation pain (0-100 mm visual analogue scale). Convenience
      of anaesthetic use and patient satisfaction were measured using a five-point
      Likert scale. RESULTS: One hundred and ten patients were enrolled in each group.
      The groups did not differ in age, gender, cannulation anxiety, cannulator
      experience, cannulation indication or site, or cannula size. Median anaesthetic
      administration pain scores were 0 and 11 mm in the vapocoolant and lidocaine
      groups, respectively (P<0.001). Median cannulation pain scores were 9 and 0 mm,
      respectively (P<0.001). Vapocoolant was associated with greater cannulation
      success (83.6% vs 67.3%, P=0.005), less time to administer (median 9.0 vs 84.5 s,
      P<0.001), and more staff convenience (median 5 vs 4, P<0.001). Median patient
      satisfaction was 4 in both groups. Unexpected events were rare and minor.
      CONCLUSIONS: Although vapocoolant reduces cannulation pain less than lidocaine,
      it has a number of important advantages. Vapocoolant offers a useful alternative
      in the emergency department setting.

PMID- 20682574
TI  - Did Drosera evolve long scapes to stop their pollinators from being eaten?
AB  - BACKGROUND AND AIMS: Insectivorous plants frequently display their flowers on the
      ends of long racemes. Conventional wisdom is that long racemes in insectivorous
      plants have evolved to provide spatial separation between flowers and traps,
      which consequently prevents pollinators from being captured. However, it is also
      possible that long racemes evolved for better seed dispersal or to make flowers
      more visible to pollinators. METHODS: Two sympatric insectivorous plants with
      identical pollinators were studied: Drosera cistiflora, with an upright growth
      form but a short raceme; and Drosera pauciflora, with a basal rosette of traps
      and a very long raceme. If long racemes evolved to protect their pollinators then
      D. cistiflora should capture more pollinators than D. pauciflora. However, if
      long racemes evolved to attract pollinators then taller flowers should receive
      more pollination visits than shorter flowers. KEY RESULTS: Examination of D.
      pauciflora and D. cistiflora traps revealed that no pollinators were captured by
      either species, suggesting that long racemes did not evolve to protect
      pollinators from being captured. Experimental manipulations of flower height in
      D. cistiflora showed that experimentally shortened plants received significantly
      fewer pollination visits than plants which were taller in stature. CONCLUSIONS:
      Long scapes in Drosera and non-insectivorous plants probably evolved due to
      similar selective pressures such as pollinator attraction.

PMID- 20682575
TI  - Mixed mating system in the fern Asplenium scolopendrium: implications for
      colonization potential.
AB  - BACKGROUND AND AIMS: Human-mediated environmental change is increasing selection
      pressure for the capacity in plants to colonize new areas. Habitat fragmentation
      combined with climate change, in general, forces species to colonize areas over
      longer distances. Mating systems and genetic load are important determinants of
      the establishment and long-term survival of new populations. Here, the mating
      system of Asplenium scolopendrium, a diploid homosporous fern species, is
      examined in relation to colonization processes. METHODS: A common environment
      experiment was conducted with 13 pairs of sporophytes, each from a different
      site. Together they constitute at least nine distinct genotypes, representing an
      estimated approx. 95 % of the non-private intraspecific genetic variation in
      Europe. Sporophyte production was recorded for gametophytes derived from each
      parent sporophyte. Gametophytes were grown in vitro in three different ways: (I)
      in isolation, (II) with a gametophyte from a different sporophyte within the same
      site or (III) with a partner from a different site. KEY RESULTS: Sporophyte
      production was highest in among-site crosses (III), intermediate in within-site
      crosses (II) and was lowest in isolated gametophytes (I), strongly indicating
      inbreeding depression. However, intragametophytic selfing was observed in most of
      the genotypes tested (eight out of nine). CONCLUSIONS: The results imply a mixed
      mating system in A. scolopendrium, with outcrossing when possible and occasional
      selfing when needed. Occasional intragametophytic selfing facilitates the
      successful colonization of new sites from a single spore. The resulting
      sporophyte, which will be completely homozygous, will shed large amounts of
      spores over time. Each year this creates a bed of gametophytes in the vicinity of
      the parent. Any unrelated spore which arrives is then selectively favoured to
      reproduce and contribute its genes to the new population. Thus, while selfing
      facilitates initial colonization success, inbreeding depression promotes
      genetically diverse populations through outcrossing. The results provide further
      evidence against the overly simple dichotomous distinction of fern species as
      either selfing or outcrossing.

PMID- 20682576
TI  - Plant resource-use strategies: the importance of phenotypic plasticity in
      response to a productivity gradient for two subalpine species.
AB  - BACKGROUND AND AIMS: Functional traits are indicators of plant interactions with
      their environment and the resource-use strategies of species can be defined
      through some key functional traits. The importance of genetic variability and
      phenotypic plasticity in trait variations in response to a common environmental
      change was investigated in two subalpine species. METHODS: Two species with
      contrasted resource-use strategies, Dactylis glomerata and Festuca paniculata,
      were grown along a productivity gradient in a greenhouse experiment. Functional
      traits of different genotypes were measured to estimate the relative roles of
      phenotypic plasticity and genetic variability, and to compare their levels of
      phenotypic plasticity. KEY RESULTS: Trait variability in the field for the two
      species is more likely to be the result of phenotypic plasticity rather than of
      genetic differentiation between populations. The exploitative species D.
      glomerata expressed an overall higher level of phenotypic plasticity compared
      with the conservative species F. paniculata. In addition to different amplitudes
      of phenotypic plasticity, the two species differed in their pattern of response
      for three functional traits relevant to resource use (specific leaf area, leaf
      dry matter content and leaf nitrogen content). CONCLUSIONS: Functional trait
      variability was mainly the result of phenotypic plasticity, with the exploitative
      species showing greater variability. In addition to average trait values, two
      species with different resource-use strategies differed in their plastic
      responses to productivity.

PMID- 20682577
TI  - Gluconeogenesis continues in premature infants receiving total parenteral
      nutrition.
AB  - OBJECTIVE: To determine the contribution of total gluconeogenesis to glucose
      production in preterm infants receiving total parenteral nutrition (TPN)
      providing glucose exceeding normal infant glucose turnover rates. STUDY DESIGN:
      Eight infants (0.955+/-0.066 kg, 26.5+/-0.5 weeks, 4+/-1 days) were studied while
      receiving routine TPN. The glucose appearance rate (the sum of rates of glucose
      infusion and residual glucose production) and gluconeogenesis were measured by
      stable isotope-gas chromatography-mass spectrometry techniques using deuterated
      water and applying the Chacko and Landau methods. RESULTS: Blood glucose ranged
      from 5.2 to 14.3 mmol/l (94-257 mg/dl) and the glucose infusion rate from 7.4 to
      11.4 mg/kg per min, thus exceeding the normal glucose production rates (GPR) of
      newborn infants in most of the babies. The glucose appearance rate was 12.4+/-0.6
      and GPR 2.1+/-0.3 mg/kg per min. Gluconeogenesis as a fraction of the glucose
      appearance rate was 11.2+/-1.1% (Chacko) and 10.5+/-1.2% (Landau) (NS) and the
      rate of gluconeogenesis was 1.35+/-0.15 mg/kg per min (Chacko) and 1.29+/-0.14
      mg/kg per min (Landau) (NS). Gluconeogenesis accounted for 73+/-11% and 68+/-10
      (NS) of the GPR for the two methods, respectively. Gluconeogenesis and
      glycogenolysis were not affected by the total glucose infusion rate, glucose
      concentration, gestational age or birth weight. Glucose concentration correlated
      with the total glucose infusion rate and gestational age (combined R(2)=0.79,
      p=0.02). CONCLUSIONS: Gluconeogenesis is sustained in preterm infants receiving
      routine TPN providing glucose at rates exceeding normal infant glucose turnover
      rates and accounts for the major part of residual glucose production.
      Gluconeogenesis is not affected by the glucose infusion rate or blood glucose
      concentration.

PMID- 20682578
TI  - Exercise echocardiography in hypertrophic cardiomyopathy.

PMID- 20682579
TI  - Teratogenic effects of HESA-A, a natural anticancer product from Iran, in mice.
AB  - HESA-A is a natural product containing herbal and marine animal substances, which
      has been patented in Iran. It has shown antioxidant, cytotoxic and anticancer
      effects. The aim of this study was to evaluate the teratogenic effects of HESA-A
      in mice. HESA-A (50, 100, 200, 400 and 800 mg/kg) was administered orally to
      pregnant mice on days 6 to 14 of gestation. Mouse reproductive developmental
      toxicity study was performed according to the ICH guideline. Embryos from the
      treated dam were sectioned and studied for external morphological abnormalities
      and skeletal malformations. HESA-A at two doses (400 and 800 mg/kg) slowed weight
      gain of pregnant mice. These two doses of HESA-A led to reduction in uterus
      weight (17% and 20% for the 400 and 800 mg/kg doses, respectively), increase in
      post-implantation resorption (150% and 200%, respectively), reduction in fetus
      weight (22% and 32%, respectively) and crown-lump length (15% and 19%,
      respectively). HESA-A at 400 and 800 mg/kg doses caused mild external and
      skeletal malformation significantly higher than the normal saline group. However,
      higher doses caused embryo malformations such as short limbs, spinal
      abnormalities, dermal cysts, microphtalmia and cleft palate. According to this
      study, only higher doses of HESA-A, which are 20 to 40 times higher than the
      usual therapeutic doses based on body surface conversion, may cause embryonic
      toxicity. This provides a reasonable safety margin for the use of HESA-A in
      pregnancy. Mechanisms of these abnormalities are not clear and need to be
      determined.

PMID- 20682580
TI  - Systemic lupus erythematosus complicated with pulmonary hemorrhage in a 17-year
      old female.
AB  - Pulmonary hemorrhage is a rare and life-threatening complication of systemic
      lupus erythematosus. In this report, we described a 17-year-old female with
      pulmonary hemorrhage as an initial manifestation of systemic lupus erythematosus,
      along with lupus nephritis and central nervous system lupus. High doses of
      corticosteroids and pulse cyclophosphamide therapy resulted in rapid improvement
      of respiratory function in our patient.

PMID- 20682582
TI  - Biomechanical comparisons of four-strand tendon repairs with double-stranded
      sutures: effects of different locks and suture geometry.
AB  - Multi-strand repairs are often used in flexor tendon surgery. We evaluated the
      strength of four four-strand tendon repairs with different locks and suture
      geometry. Forty-eight pig flexor tendons were repaired with the following
      methods: a cross-lock four-strand repair; a U-shaped repair with circle-locks; a
      modified Kessler repair with Pennington locks (with longitudinal sutures located
      more centrally; and another modified Kessler (with longitudinal sutures located
      more laterally). The tendons were loaded to complete failure of the repairs. The
      two Kessler repairs showed a 35% lower 2 mm gap force, and 15% lower ultimate
      strength compared with the other two repairs; the differences were of statistical
      significance. The failure pattern was breakage of sutures in almost all tendons.
      These four-strand repairs differed in gapping and ultimate strengths. The Kessler
      type repairs with different geometry in the longitudinal sutures produced
      identical strengths. The Kessler-type repairs with Pennington locks were weaker
      than the two repairs with either cross-locks or circle-locks.

PMID- 20682583
TI  - The wash-out technique in the management of delayed presentations of
      extravasation injuries.
AB  - Late presentation of extravasation injuries from chemotherapeutic agents is not
      uncommon. Twenty-four patients with extravasation injuries presented with upper
      limb extravasation but without any skin necrosis between the second and the
      fourteenth day following injury day. We flushed out the infiltrated area with 300
      500 ml of normal saline through multiple stab incisions. All 24 patients
      responded well to the procedure and no further complications occurred. The
      average time for the complete healing of the wounds was 15 days. All the patients
      were able to continue their chemotherapy treatment without delay. Patients were
      followed up for a mean period of 13 months. They all recovered with no functional
      deficit and only mild scarring. Early recognition and immediate treatment of
      extravasation injuries are of paramount importance. In cases with no evidence of
      skin necrosis, a delayed wash-out procedure appears to be very effective in
      removing the extravasated drug and minimizing further tissue damage.

PMID- 20682584
TI  - Defined particle ligands trigger specific defense mechanisms of macrophages.
AB  - Phagocytosis is a receptor-mediated process for sequestration and inactivation of
      infectious microbes. It can be triggered by microbial surface compounds or
      particle-attached host proteins. We monitored the effector functions of murine
      bone marrow-derived macrophages (BMMs) in response to polystyrene-streptavidin
      beads coated with the defined ligands IgG1, beta-glucan, mannan, complement
      factors C1q or iC3b, or fibronectin (FN). Cell-autonomous effector mechanisms
      (uptake, phagosome maturation, cytokine responses and killing activity) were
      differentially triggered. All particle-ligand complexes stimulated the release of
      nitric oxide, but only beads coated with IgG, complement factors or FN caused
      production of superoxide. Beads coated with C1q, iC3b or FN strongly stimulated
      the secretion of pro-inflammatory TNF-alpha, IL-6, and IL-1beta and also of anti
      inflammatory IL-10. Escherichia coli coated with C1q, iC3b or FN was killed much
      less efficiently than with any of the other ligands, depending on the presence of
      IL-10 activity. This indicated an important role of IL-10 as regulator of cell
      autonomous immune functions of macrophages. Our data show that defined ligands on
      microbial surfaces are interesting candidates to activate innate defense
      mechanisms selectively and specifically.

PMID- 20682585
TI  - Role of calcium in lipopolysaccharide-induced calcitonin gene expression in human
      adipocytes.
AB  - Severe systemic infections induce ubiquitous calcitonin (CALC) gene expression
      with release of calcitonin peptides, namely procalcitonin, calcitonin gene
      related peptide and adrenomedullin. Using an in vitro model for bacterial
      infection, we tested the hypothesis that intracellular calcium concentration
      ([Ca(2+)](i)) is elevated after lipopolysaccharide (LPS) stimulation and is
      responsible for the LPS-mediated increase in CALC gene expression and protein
      secretion. In our human adipocyte model, LPS did not show any cytotoxic effects
      and induced increased CALC-I gene mRNA expression. Additionally, LPS provoked an
      elevation in [Ca(2+)](i). The LPS-induced increase in CALC-I gene mRNA was
      partially blocked with verapamil, an L-type calcium channel blocker and blocked
      almost completely with 2-aminoethoxydiphenyl borate, a blocker of store-operated
      calcium entry and inositol triphosphate-mediated calcium release. Treatment of
      cells with substances elevating [Ca(2+)]( i) led to an increased CALC-I mRNA
      expression level. The combination of LPS with substances raising [Ca(2+)](i) even
      potentiated this increase. At the same time, elevated [Ca(2+)](i) attenuated the
      expression level of the CALC-V gene. These findings indicate that, in human
      adipocytes, changes in [Ca(2+)](i) are involved in LPSregulated expression of
      CALC genes, thereby strengthening previous findings postulating a crucial role of
      intracellular calcium homeostasis in the state of bacterial infection and sepsis.

PMID- 20682586
TI  - Mitogen-activated protein kinases p38 and ERK1/2 regulated control of
      Mycobacterium avium replication in primary murine macrophages is independent of
      tumor necrosis factor-alpha and interleukin-10.
AB  - In macrophages, mitogen-activated protein kinases (MAPK) are critical regulators
      of both, mycobacterial replication and mycobacteria-induced cytokine formation.
      To segregate direct effects of MAPK function on mycobacterial replication from
      indirect, cytokine-mediated effects, we studied the growth of Mycobacterium avium
      strains in wild-type and tumor necrosis factor (TNF)-alpha- or interleukin (IL)
      10-deficient bone marrow-derived murine macrophages. Using specific inhibitors of
      the p38- and the ERK1/2-MAPK pathways, we found that the use of SB203580 always
      reduced, whereas the presence of PD98059 always promoted, bacterial replication
      of highly virulent and intermediately virulent M. avium strains, independent of
      endogenous TNF-alpha or IL-10. The exogenous addition of TNF-alpha to TNF-alpha
      deficient and wild-type M. avium-infected macrophages overrode the replication
      reducing effect of SB203580, but not the replication-promoting effect of PD98059.
      In summary, our data demonstrate that a proper balance of MAPK activity is
      essential for macrophage control of M. avium growth, and that the ratio of the
      cytokines TNF-alpha and IL-10 can additionally modulate replication. Our findings
      indicate a novel therapeutic avenue for treating mycobacterial infections in
      particular by stimulating ERK1/2 or activating ERK1/2-dependent mechanisms in
      infected macrophages.

PMID- 20682587
TI  - Activation of cytokine-producing and antitumor activities of natural killer cells
      and macrophages by engagement of Toll-like and NOD-like receptors.
AB  - Macrophages and natural killer (NK) cells are important antitumor effectors by
      virtue of their ability to produce cytokines, chemokines and interferons (IFNs)
      and to mediate tumor cytotoxicity. Little is known about the impact of Toll-like
      receptor (TLR) and nucleotide binding and oligomerization domain (NOD)-like
      receptor (NLR) pathways on NK cell functions, and the role of TLRs and NLRs in
      macrophage activation is incompletely understood. In this study, we examined the
      capacities of expressed TLRs and NLRs to elicit cytokine production in human NK
      cells and THP1 macrophages, and to activate NK cytotoxicity against the squamous
      cell carcinoma of head and neck cell line Tu167 and erythroleukemia K562 cells.
      We found that NK cells express high levels of NOD2, NLRP3, TLR3, TLR7, and TLR9,
      while NOD1 was expressed at low levels. All tested NLR and TLR agonists
      potentiated NK cytotoxicity against Tu167 cells, whereas only poly (I:C)
      increased NK cytotoxicity against K562 cells. Poly (I:C) and Escherichia coli RNA
      markedly up-regulated TNF-alpha and IFN-gamma expression in the NK92 cell line
      and human CD56(+)CD3(-) primary NK cells. High levels of NOD2, TLR7 and TLR9
      proteins were observed in human THP1 cells, followed by TLR3, NOD1, and NLRP3.
      Stimulation of NLRP3 with E. coli RNA led to the highest induction of TNF-alpha,
      IL-6, IL-12p40, RANTES and IFN-beta, whereas TLR7, TLR3, TLR9, NOD1 and NOD2
      agonists had lower effects. Our data reveal involvement of TLRs and NLRs in
      potentiation of antitumor cytotoxicity and cytokine-producing activities of human
      NK cells and macrophages.

PMID- 20682588
TI  - Morphology, size distribution, and aggregate structure of lipopolysaccharide and
      lipid A dispersions from enterobacterial origin.
AB  - Lipopolysaccharides (LPSs) from Gram-negative bacteria are strong elicitors of
      the human immune systems. There is strong evidence that aggregates and not
      monomers of LPS play a decisive role at least in the initial stages of cell
      activation of immune cells such as mononuclear cells. In previous reports, it was
      shown that the biologically most active part of enterobacterial LPS, hexa-acyl
      bisphosphorylated lipid A, adopts a particular supramolecular conformation, a
      cubic aggregate structure. However, little is known about the size and morphology
      of these aggregates, regarding the fact that LPS may have strong variations in
      the length of the saccharide chains (various rough mutant and smooth-form LPS).
      Thus, in the present paper, several techniques for the determination of details
      of the aggregate morphology such as freeze-fracture and cryo-electron microscopy,
      analytical ultracentrifugation, laser backscattering analysis, and small-angle X
      ray scattering were applied for various endotoxin (lipid A and different LPS)
      preparations. The data show a variety of different morphologies not only for
      different endotoxins but also when comparing different applied techniques. The
      data are interpreted with respect to the suitability of the single techniques, in
      particular on the basis of available literature data.

PMID- 20682589
TI  - Distinct regulation by lipopolysaccharides of the expression of interleukin-1beta
      by murine macrophages and salivary glands.
AB  - The regulation of interleukin (IL)-1 expression and secretion by salivary glands
      and macrophages in response to lipopolysaccharides (LPS) was compared. In wild
      type mice, injection of LPS significantly decreased the volume of saliva
      stimulated by pilocarpine and increased its protein and amylase concentration. It
      did not modify the salivary concentration of IL-1beta. The cytokine was expressed
      by submandibular acini and ducts. Macrophages also expressed IL-1beta but at
      lower concentration than salivary glands. The pre-incubation of macrophages with
      LPS increased the phosphorylation of IkappaB and the expression of IL-1beta.
      Adenosine triphosphate also promoted the secretion of the cytokine by these
      cells. These responses were absent in submandibular gland cells. These glands
      expressed CD14, TLR4 and MyD88. P2X(7)-KO mice secreted a lower volume of saliva
      which contained less proteins and amylase. In conclusion, IL-1beta is
      constitutively expressed by submandibular glands and its secretion is not
      regulated by a P2X(7) agonist. In these cells, LPS do not activate the nuclear
      factor-kappaB-pro-IL-1beta axis in spite of the expression of the proteins
      involved in their recognition.

PMID- 20682590
TI  - Temperament influences endotoxin-induced changes in rectal temperature, sickness
      behavior, and plasma epinephrine concentrations in bulls.
AB  - This study was designed to determine the influence of temperament on endotoxin
      induced changes in body temperature, sickness behavior, and stress hormone
      concentrations in cattle. Brahman bulls were selected based on temperament score
      measured 28 d prior to weaning. In dwelling recording devices were used to
      monitor rectal temperature, and jugular catheters were used to collect blood
      samples to determine cortisol and epinephrine concentrations before and after LPS
      administration (0.5 MUg/kg body weight). Temperamental bulls had the lowest peak
      rectal temperature and sickness behavior scores relative to the Calm and
      Intermediate bulls. Prior to the administration of LPS, Temperamental bulls had
      greater cortisol and epinephrine concentrations than Calm or Intermediate bulls.
      Cortisol concentrations increased following LPS administration but were not
      affected by temperament. Epinephrine concentrations peaked 1 h after LPS
      administration in Calm bulls. Temperamental bulls did not exhibit an epinephrine
      response to LPS challenge. These data demonstrate that the temperament of calves
      can modulate the physiological, behavioral, and endocrine responses of pre
      pubertal Brahman bulls to endotoxin challenge. Specifically, temperament
      differentially affected the rectal temperature, sickness behavior and
      epinephrine, but not cortisol, responses to LPS challenge.

PMID- 20682591
TI  - Diagnostic efficacy of gadoxetic acid-enhanced MRI in the detection of
      hepatocellular carcinomas: comparison with gadopentetate dimeglumine.
AB  - This study compared the efficacy of gadoxetic acid-enhanced MRI and gadopentetate
      dimeglumine-enhanced MRI in the detection of small hepatocellular carcinoma
      (HCC). Both MRI techniques were performed on 43 patients with a total of 59 HCCs
      (size range, 0.5-2.0 cm), with a mean interval between the two MRI studies of 3
      days (range, 2-7 days). Two observers reviewed both data sets in consensus.
      Diagnostic accuracy and sensitivity were evaluated using the alternative-free
      response receiver operator characteristic (ROC) method. The gadoxetic acid set
      showed a trend toward increased area under the ROC curve (Az value = 0.958)
      compared with the gadopentetate dimeglumine set (Az value = 0.927), but the
      difference was not significant (p = 0.362). The sensitivity of the gadoxetic acid
      set (n = 51, 86.4%) was significantly higher than that of the gadopentetate
      dimeglumine set (n = 38, 64.4%) (p = 0.0001). Gadoxetic acid-enhanced MRI is a
      more sensitive diagnostic tool for detection of HCC than gadopentetate
      dimeglumine-enhanced MRI.

PMID- 20682592
TI  - Correlation between mammographic and sonographic findings and prognostic factors
      in patients with node-negative invasive breast cancer.
AB  - OBJECTIVES: The purpose of this study was to correlate sonographic and
      mammographic findings with prognostic factors in patients with node-negative
      invasive breast cancer. METHODS: Sonographic and mammographic findings in 710
      consecutive patients (age range 21-81 years; mean age 49 years) with 715 node
      negative invasive breast cancers were retrospectively evaluated. Pathology
      reports relating to tumour size, histological grade, lymphovascular invasion
      (LVI), extensive intraductal component (EIC), oestrogen receptor (ER) status and
      HER-2/neu status were reviewed and correlated with the imaging findings.
      Statistical analysis was performed using logistic regression analysis and
      intraclass correlation coefficient (ICC). RESULTS: On mammography, non-spiculated
      masses with calcifications were associated with all poor prognostic factors: high
      histological grade, positive LVI, EIC, HER-2/neu status and negative ER. Other
      lesions were associated with none of these poor prognostic factors. Hyperdense
      masses on mammography, the presence of mixed echogenicity, posterior enhancement,
      calcifications in-or-out of masses and diffusely increased vascularity on
      sonography were associated with high histological grade and negative ER.
      Associated calcifications on both mammograms and sonograms were correlated with
      EIC and HER-2/neu overexpression. The ICC value for the disease extent was 0.60
      on mammography and 0.70 on sonography. CONCLUSION: Several sonographic and
      mammographic features can have a prognostic value in the subsequent treatment of
      patients with node-negative invasive breast cancer. Radiologists should pay more
      attention to masses that are associated with calcifications because on both
      mammography and sonography associated calcifications were predictors of positive
      EIC and HER-2/neu overexpression.

PMID- 20682593
TI  - Brachytherapy for tongue cancer in the very elderly is an alternative to external
      beam radiation.
AB  - BACKGROUND: The result of curative treatment for very elderly patients with
      tongue carcinoma has not been reported to date. We retrospectively reviewed the
      results of brachytherapy in 125 the patients aged over 75 years. METHODS: The
      results of brachytherapy in 125 patients, 75 years old or older, with Stage I or
      II squamous cell carcinoma of the oral tongue were reviewed. The 125 cases
      consisted of 31 Stage I and 94 Stage II cases; 67 patients were under 80 years
      old and 58 were over 80 years old. All patients were treated using low-dose-rate
      brachytherapy ((198)Au/(222)Rn: 59 cases; (192)Ir: 38 cases; (226)Ra/(137)Cs: 28
      cases). RESULTS: None of the patients stopped treatment during the course of
      brachytherapy. The 3 year and 5 year control rates of the primary lesions were
      both 86%. Post-brachytherapy neck node metastasis was diagnosed in 43 cases and
      radical neck dissection was performed for 24 cases (21 of the 24 cases were under
      80 years old). As a result, the 7 year disease-specific survival (DSS) rate for
      patients aged under 80 years old was 70% and 41% for those over 80 years old (p =
      0.03). CONCLUSION: The brachytherapy for elderly patients with tongue cancer was
      safe, and the control of the primary lesion was almost the same as in younger
      patients. However, modalities available to treat neck node metastasis are
      limited. More conservative surgical approaches combined with post-operative
      irradiation may be advocated for neck node metastasis for elderly patients with
      tongue cancer.

PMID- 20682594
TI  - Concurrent celiac disease, idiopathic thrombocytopenic purpura and autoimmune
      thyroiditis: a case report.
AB  - Celiac disease (CD) is a disease of the small intestine caused by an immune
      response to ingested gluten. Idiopathic thrombocytopenic purpura (ITP) is a
      common acquired bleeding disorder of childhood. It may follow a viral infection
      or immunization and is caused by an inappropriate response of the immune system.
      Autoimmune thyroiditis (AT) is a disease that occurs due to autoimmune
      mechanisms. Celiac disease associated with autoimmune thyroid disease is well
      known, but the association of CD, autoimmune thyroid disease, and ITP has been
      reported very rarely in the literature. In the current report, we have presented
      a case with CD, AT, and acute ITP, because this association is rarely seen, and
      to emphasize that CD and AT should be kept in mind in patients with ITP.

PMID- 20682595
TI  - Increased mean platelet volume in patients with aortic stenosis.
AB  - BACKGROUND: Systemic thromboembolism is a serious complication in patients with
      aortic stenosis (AS). Previous studies have demonstrated that platelet activation
      occurs in patients with AS. The aim of this study was to assess the mean platelet
      volume (MPV), an indicator of platelet activation in patients with AS. PATIENTS
      AND METHODS: The study group consisted of 43 patients with AS. An age-, gender-,
      and body mass index-matched control group consisted of 35 healthy volunteers. All
      patients and control participants underwent echocardiographic examination. We
      measured the serum MPV values in patients and control participants. RESULTS: Mean
      platelet volume was significantly higher among patients with AS when compared
      with the control group (8.7 +/- 1.0 vs 7.9 +/- 0.9 fL, respectively; P = .001).
      CONCLUSION: We have shown that MPV was significantly elevated in patients with AS
      compared to control participant.

PMID- 20682596
TI  - Disseminated intravascular coagulation in a case of brucellosis.
AB  - Brucellosis is a multisystem disease with a broad spectrum of clinical
      manifestations; hematological abnormalities ranging from fulminant as of
      disseminated intravascular coagulation (DIC) to anaemia, leucopoenia,
      thrombocytopenia, and clotting disorders. In this report, we present DIC in a
      case of brucellosis because of rare presentation. A 3-year-old boy was admitted
      with the complaints of continuous fever, vomiting, abdominal pain, and bruise on
      leg. He looked pale and his physical examination revealed purpuric skin lesions
      on both legs. A mild hepatosplenomegaly was noted on palpation. Laboratory tests
      showed hematocrit 21%, hemoglobin 7 g/dL, platelet count 20,000/mm(3),
      prothrombin time 19 seconds, activated partial thromboplastin time 48 seconds,
      plasma fibrinogen level 20 mg/dL, and D-dimer 8 ug/mL. Serum antibrucella
      titration agglutination test was found to be 1 of 1280 positive. Blood cultures
      performed on specimens obtained at the time of admission yielded Brucella
      melitensis. The clinical and laboratory findings were consistent with DIC.

PMID- 20682597
TI  - Different effects of enoxaparin, nadroparin, and dalteparin on plasma TFPI during
      hemodialysis: a prospective crossover randomized study.
AB  - BACKGROUND: Low-molecular-weight heparins (LMWHs) are an alternative to
      unfractionated heparin (UFH) for anticoagulation during hemodialysis (HD). We
      performed a prospective randomized crossover study of the effect of enoxaparin,
      nadroparin, and dalteparin on some hemostatic factors, including tissue factor
      pathway inhibitor (TFPI), in patients with maintenance HD. METHODS: Plasma levels
      (immunoassays) of total TFPI, platelet-derived growth factor-AB (PDGF-AB), and
      prothrombin fragment 1 + 2 (PF 1 + 2) were evaluated pre-HD, after 10 (T10) and
      180 (T180) minutes of HD in 21 patients, who completed a 3-period (for 2 months
      each) crossover study in 6 groups (Latin-square design). RESULTS: The baseline
      TFPI, PDGF-AB, and PF 1 + 2 levels were comparable under all LMWH treatments.
      Tissue factor pathway inhibitor levels, compared with the baseline, significantly
      increased (all P < 10(-4)), whereas PDGF-AB levels remained stable at each
      interval during enoxaparin, nadroparin, and dalteparin anticoagulated HD.
      Interestingly, TFPI increment at T10 was the highest, dose-dependent, and
      accompanied by PF 1 + 2 decrease under enoxaparin administration. CONCLUSION: The
      switch from enoxaparin to nadroparin and dalteparin used as anticoagulants had no
      long-term effect on the baseline total TFPI and PF 1 + 2 levels in chronically HD
      patients. Only short-term, overdialytic differences were noticed, indicating a
      single bolus of enoxaparin (0.75 mg/kg) as the most potent stimulus for
      endothelial TFPI.

PMID- 20682598
TI  - Influence of long-term thromboprophylaxis with low-molecular-weight heparin
      (enoxaparin) on changes of bone metabolism markers in pregnant women.
AB  - This is a first descriptive, retrospective, observational study aiming to
      evaluate the changes in bone turnover markers in pregnant women and to assess the
      effect of a long-term treatment with low-molecular-weight heparin (LMWH),
      specifically, enoxaparin. Study involved 50 pregnant Caucasian women with
      thrombophilia. The patients either received prophylactic enoxaparin once daily
      subcutaneously (N = 35) or were observed without treatment (N = 15).
      Concentrations of total serum alkaline phosphatase (total AP), bone alkaline
      phosphatase (bone AP), osteoprotegerin (OPG), and the receptor activator of
      nuclear factor kappaB ligand (RANKL) were measured at 15, 25, and 35 weeks of
      gestation. Total serum AP increased with gestational age. In the group treated
      with enoxaparin, the percentage of bone AP concentration was lower (P < .05) than
      in the control group. Serum OPG also increased with gestational age, but no
      significant difference was found between the groups with- and without treatment.
      Despite the OPG increased, RANKL did not change.

PMID- 20682599
TI  - Polymorphisms and mutations in vWF and ADAMTS13 genes and their correlation with
      plasma levels of FVIII and vWF in patients with deep venous thrombosis.
AB  - BACKGROUND: Increased levels of factor VIII (FVIII) are a prevalent and
      independent risk factor for deep venous thrombosis (DVT) and are affected by von
      Willebrand factor (vWF) levels. DESIGN AND METHODS: ADAMTS13 contributes to vWF
      levels, and we investigated genetic polymorphisms previously described to be
      associated with decreased levels of these proteins in 435 patients with DVT (126
      M and 309 F; median age 37 years, range 18-68 years) and 580 controls (163 M and
      417 F; median age 35 years, range 18-68 years). Subsequently, we investigated the
      relationship between the genotypes and plasma levels of FVIII, vWF, and DVT risk.
      RESULTS: Patients with DVT showed higher plasma levels of FVIII:C, FVIII:Ag, and
      vWF:Ag (P < .001) when compared to controls. Patients and controls heterozygous
      for the 4751A>G polymorphism in the vWF gene presented decreased levels of
      vWF:Ag, FVIII:Ag, and FVIII:C (P < .001), but this was not a protective factor
      for DVT. Individuals heterozygous for 1852C>G polymorphism in ADAMTS13 gene,
      which is associated with reduced levels of ADAMTS13, had significantly elevated
      levels of vWF:Ag (P = .001), FVIII:Ag (P = .01), and FVIII:C (P = .02). However,
      this polymorphism was not a risk factor for DVT in our study. Heterozygosis for a
      new polymorphism identified in ADAMTS13 gene, 1787-26G>A, was significantly
      associated with elevated levels of FVIII:C (P = .02) when compared to wild type.
      CONCLUSIONS: Despite the tempting assumption that genetic factors that change
      ADAMTS13 activity might modulate the risk of DVT by altering vWF and FVIII
      levels, the polymorphisms analyzed in this study did not correlate with DVT risk
      among patients investigated.

PMID- 20682600
TI  - Matrix metalloproteinases are possible mediators for the development of
      alimentary tract mucositis in the dark agouti rat.
AB  - Alimentary tract (AT) mucositis is a serious and debilitating side-effect of
      cancer therapy primarily characterized by damage of the mucous membranes
      throughout the AT. It is well established that this damage is a result of up
      regulation of stress response genes and pro-inflammatory cytokines. Matrix
      metalloproteinases (MMPs) have been shown to function in several of the pathways
      known to be up-regulated in mucositis and play a key role in tissue injury and
      inflammation in many gastrointestinal disorders. This study aims to characterize
      the expression of multiple MMPs including MMP-1, -2, -3, -9 and -12 and their
      inhibitors, tissue inhibitor of metalloproteinase (TIMP)-1 and -2, in a rat model
      of irinotecan-induced mucositis. Dark agouti rats were administered a single 200
      mg/kg intraperitoneal dose of irinotecan and killed at 1, 6, 24, 48, 72, 96 and
      144 h following treatment. Hematoxylin and eosin staining, immunohistochemistry
      and realtime polymerase chain reaction were used to assess histopathological
      damage and MMP expression in the jejunum and colon. Marked histopathological
      evidence of mucositis was observed in the jejunum and colon as early as six hours
      following irinotecan treatment. A significant alteration in both gene expression
      and tissue levels of MMPs and TIMPs was noted following irinotecan. The increase
      in MMP-2, -3, -9 and -12 levels was associated with inflammatory infiltrate and
      maximum tissue damage. In contrast, MMP-1 expression correlated with tissue
      restitution. TIMP-1 and -2 levels were significantly altered in the jejunum
      following irinotecan. The augmentation in the expression profiles of MMPs and
      their inhibitors correlated with histopathological alterations observed in the
      tissue following irinotecan. This prompts the consideration of MMPs as possible
      mediators of chemotherapy-induced mucositis.

PMID- 20682601
TI  - Diamide decreases deformability of rabbit erythrocytes and attenuates low oxygen
      tension-induced ATP release.
AB  - Exposure of erythrocytes to reduced oxygen (O(2)) tension activates the
      heterotrimeric G-protein Gi, resulting in the accumulation of cyclic AMP (cAMP)
      and release of ATP. The mechanism by which exposure of erythrocytes to reduced
      O(2) tension activates Gi is not known. Here we investigate the hypothesis that,
      in rabbit erythrocytes, ATP release in response to exposure to reduced O(2)
      tension is linked to erythrocyte membrane deformability. If this hypothesis is
      correct, then decreasing the deformability of the erythrocyte membrane should
      decrease the release of ATP in response to reduced O(2) tension. We report that
      treating erythrocytes with diamide, a compound that decreases erythrocyte
      deformability, inhibits low O(2) tension-induced ATP release. Treating
      erythrocytes with diamide does not, however, interfere with cAMP accumulation or
      ATP release in response to a direct activator of Gi (mastoparan 7) or in response
      to receptor-mediated activation of Gs (the prostacyclin analog, iloprost). These
      results demonstrate that diamide (100 micromol/L) does not directly inhibit the
      signaling pathways for ATP release from rabbit erythrocytes and support the
      hypothesis that low O(2) tension-induced ATP release from these cells is linked
      to membrane deformability.

PMID- 20682602
TI  - Delivery of TFPI-2 using SonoVue and adenovirus results in the suppression of
      thrombosis and arterial re-stenosis.
AB  - Genes could be used to treat atherosclerosis. The key problem is how to target a
      gene through the walls of arteries in free-flowing blood. TFPI-2 has been shown
      to suppress thrombosis and arterial re-stenosis, which indicates its potential
      function in gene therapy for atherosclerosis. The microbubble ultrasound contrast
      agent is widely applied in diagnostic imaging, and could be used for transferring
      genes into arteries. By transfecting TFPI-2 into arteries using SonoVue (a kind
      of microbubble ultrasound contrast agent), we identified TFPI-2 as an available
      factor for inhibiting the proliferation of vascular endothelial cells in vivo.
      Compared with adenovirus, SonoVue showed similar gene transfection efficiency,
      but the latter showed stronger inhibition of thrombosis and arterial re-stenosis
      with a high expression of TFPI-2 protein in vitro and in vivo. SonoVue was less
      damaging when transfecting genes into the arterial wall. These data indicate that
      transfecting human TFPI-2 into the arterial wall may suppress thrombosis and
      arterial re-stenosis, and reduce atherosclerosis.

PMID- 20682603
TI  - Mannose-binding lectin (MBL2) and ficolin-2 (FCN2) polymorphisms in patients on
      peritoneal dialysis with staphylococcal peritonitis.
AB  - BACKGROUND: Mannose-binding lectin (MBL) and ficolin-2 (FCN) are activators of
      the lectin pathway of complement and act as primary defences against infection.
      Single-nucleotide polymorphisms (SNPs) in the MBL2 and FCN2 genes influence the
      functionality of the proteins. Both proteins are capable of binding
      staphylococci, which are pathogens that frequently cause peritonitis in patients
      on continuous ambulatory peritoneal dialysis (CAPD). We studied the role of
      polymorphisms in the MBL2 and FCN2 genes as a risk factor for developing CAPD
      peritonitis caused by staphylococci. METHODS: We analysed SNPs in the MBL2 and
      FCN2 genes in 40 CAPD patients with staphylococcal peritonitis and in 65 CAPD
      patients without any history of peritonitis. Additionally, we analysed the
      prevalence of exit site infections and nasal Staphylococcus aureus carriage in
      both groups. RESULTS: The + 6359C > T SNP leading to the Thr236Met amino acid
      alteration in the FCN2 gene, associated with decreased substrate binding, was
      significantly more prevalent in CAPD patients with a history of staphylococcal
      peritonitis compared with patients on CAPD without a history of peritonitis (P =
      0.037). No difference was found in MBL2 genotypes between the two groups. In CAPD
      patients with a history of staphylococcal peritonitis, exit site infection with
      S. aureus was also more prevalent (P < 0.01), while S. aureus carriage was not (P
      = 0.073). CONCLUSIONS: In addition to known risk factors such as exit site
      infection, the + 6359C > T SNP in the FCN2 gene might be a risk factor for
      staphylococcal peritonitis in CAPD patients due to decreased binding of FCN to
      staphylococci.

PMID- 20682605
TI  - The renal resistance index is increased in mild-to-moderate obstructive sleep
      apnoea and is reduced under continuous positive airway pressure.
AB  - BACKGROUND: Impaired renal function has recently been reported in obstructive
      sleep apnoea (OSA). The underlying mechanisms, however, are not entirely
      understood. This study investigated the influence of mild-to-moderate OSA and its
      treatment on renal haemodynamics as assessed by the renal resistance index (RRI).
      METHODS: RRI has been measured by colour duplex ultrasound in 64 patients with
      newly diagnosed mild-to-moderate OSA and 61 controls without OSA at baseline and
      follow-up after 9.9 months. Treatment with continuous positive airway pressure
      was offered to all patients with OSA (apnoea/hypopnoea index >= 5/h). RESULTS:
      Increased values of RRI (>= 1 SD [8.9%] above the age-adjusted normal value) were
      found in 41 out of 64 (64.0%) OSA patients when compared with 20 out of 61
      (32.8%) controls (P < 0.001). The corresponding mean RRI was 70.50 +/- 9.01 vs
      66.51 +/- 8.33 (P = 0.012). In multivariate analyses, the influence of OSA on RRI
      was independent from hypertension, diabetes mellitus, age and baseline renal
      function. At follow-up, RRI decreased only in patients with effective OSA
      treatment but remained unchanged in ineffectively treated OSA patients and
      controls. CONCLUSIONS: For the first time, this prospective controlled
      observational study demonstrates an impairment of renal haemodynamics in OSA as
      measured by an increased RRI. These changes of renal blood flow may identify OSA
      patients at high risk of declining renal function. Both parenchymal and vascular
      renal diseases are proposed as pathomechanisms for this association. An effective
      treatment of OSA resulted in a decreased RRI, suggesting an improvement in renal
      perfusion. Further studies are needed to elucidate the role of impaired renal
      haemodynamics in OSA.

PMID- 20682604
TI  - Inflammation, kidney function and albuminuria in the Framingham Offspring cohort.
AB  - BACKGROUND: Inflammation and chronic kidney disease (CKD) are both associated
      with cardiovascular disease (CVD). Whether inflammatory biomarkers are associated
      with kidney function and albuminuria after accounting for traditional CVD risk
      factors is not completely understood. METHODS: The sample comprised Framingham
      Offspring cohort participants (n = 3294, mean age 61, 53% women) who attended the
      seventh examination cycle (1998-2001). Inflammatory biomarkers [C-reactive
      protein (CRP), tumour necrosis factor (TNF)-alpha, interleukin-6, TNF receptor 2
      (TNFR2), intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant
      protein-1 (MCP-1), P-selectin, CD-40 ligand, osteoprotegerin, urinary
      isoprostanes, myeloperoxidase and fibrinogen] were measured on fasting blood
      samples. Serum creatinine-based estimated glomerular filtration rate (eGFR) and
      serum cystatin C concentration were used to assess kidney function. Urinary
      albumin-to-creatinine ratio (UACR) was used to assess albuminuria. Linear or
      logistic regression was used to test associations between biomarkers and kidney
      measures. RESULTS: Chronic kidney disease (CKD), defined as eGFR < 59/64
      mL/min/1.73 m(2) in women/men, was present in 8.8% (n = 291) of participants. TNF
      alpha, interleukin-6, TNFR2, MCP-1, osteoprotegerin, myeloperoxidase and
      fibrinogen were higher among individuals with CKD; all biomarkers except for
      urinary isoprostanes were elevated in higher cystatin C quartiles; and TNF-alpha,
      interleukin-6, TNFR2, ICAM-1 and osteoprotegerin were elevated in higher UACR
      quartiles-all assessed after multivariable adjustment. Almost 6% and 17% of
      variability in TNFR2 were explained by CKD status and higher cystatin C
      quartiles, respectively. CONCLUSIONS: Biomarkers of inflammation are associated
      with kidney function and albuminuria. In particular, substantial variability in
      soluble TNFR2 is explained by CKD and cystatin C.

PMID- 20682606
TI  - A phase II study of pazopanib in patients with recurrent or metastatic invasive
      breast carcinoma: a trial of the Princess Margaret Hospital phase II consortium.
AB  - PURPOSE: Angiogenesis is an important hallmark of breast cancer growth and
      progression. Pazopanib, an oral small molecule inhibitor of vascular endothelial
      growth factor receptor, platelet-derived growth factor receptor, and KIT, has
      activity across a range of solid tumors. We evaluated the activity of single
      agent pazopanib in recurrent or metastatic breast cancer (MBC). PATIENTS AND
      METHODS: Patients with recurrent breast cancer or MBC, treated with up to two
      prior lines of chemotherapy, were eligible to receive pazopanib, 800 mg daily
      until progression. The primary endpoint was the objective response rate as
      measured by Response Evaluation Criteria in Solid Tumors. Secondary endpoints
      included time to progression, the stable disease rate, and toxicity. Using a two
      stage design, confirmed response in three of 18 patients was required to proceed
      to stage 2. RESULTS: Twenty evaluable patients were treated, with a median age of
      56 years; 70% were estrogen receptor positive, all were human epidermal growth
      factor receptor 2 negative. The majority had one or two prior lines of
      chemotherapy. One patient (5%) had a partial response, 11 (55%) had stable
      disease (SD) [four (20%) with SD > or = 6 months], and seven (35%) had
      progressive disease as their best response. One (5%) was not evaluable. The
      median time to progression was 5.3 months. Pazopanib did not cause significant
      severe toxicity aside from grade 3-4 transaminitis, hypertension, and neutropenia
      in three patients each (14% each) and grade 3 gastrointestinal hemorrhage in one
      patient (5%). CONCLUSION: Pazopanib provides disease stability in advanced breast
      cancer. The activity seen is comparable with that of other antiangiogenic agents
      in this setting. Pazopanib may be of interest for future studies in breast
      cancer, including in combination with other systemic agents.

PMID- 20682607
TI  - Predictors of chemotherapy patients' intentions to engage in medical error
      prevention.
AB  - BACKGROUND: Patients can make contributions to the safety of chemotherapy
      administration but little is known about their motivations to participate in
      safety-enhancing strategies. The theory of planned behavior was applied to
      analyze attitudes, norms, behavioral control, and chemotherapy patients'
      intentions to participate in medical error prevention. METHODS: A quantitative,
      cross-sectional survey study among chemotherapy patients treated at the
      oncology/hematology department of a large regional hospital was conducted.
      Confirmatory factor analysis and structural equation modeling were used to
      investigate the relationship between patients' responses to measures of
      attitudes, norms, and behavioral control and their intentions. RESULTS: Four
      hundred seventy-nine patients completed the survey (52% response rate).
      Attitudes, perceived behavioral control, and subjective norms explained 62% of
      the variance in intentions to engage in error monitoring and reporting. Perceived
      behavioral control (beta = 0.476), norms relating to patients' relatives (beta =
      0.343), and instrumental attitudes (beta = 0.281) were the strongest (direct)
      predictors of patients' intentions. Experiential attitudes had the smallest
      effect on intentions (beta = 0.178). Subjective norms relating to expectations
      attributed to oncology staff had strong direct and indirect effects on patients'
      intentions (total effect, 0.382). CONCLUSIONS: Patients acknowledge the benefit
      of error monitoring and reporting and anticipate positive outcomes of
      involvement, but their valuations of the process of engaging in error prevention
      are less positive. Behavioral control and perceptions of staff approval are
      central for patients. Involvement of cancer patients in safety requires
      oncologists to address their patients' normative and control beliefs through
      education and proactive approval of patient engagement.

PMID- 20682608
TI  - Adjuvant therapy in non-small cell lung cancer: current and future directions.
AB  - The cornerstone of treatment for early-stage non-small cell lung cancer (NSCLC)
      has long been surgical resection. Over the past few years, there has been a
      paradigm shift to provide adjuvant platinum-based chemotherapy for patients with
      completely resected stage II-IIIA NSCLC founded on large randomized clinical
      trials demonstrating longer overall survival with this treatment. Reassuringly,
      the National Cancer Institute of Canada Cancer Therapeutics Group JBR.10 trial
      recently reported a continued survival advantage for patients treated with
      adjuvant chemotherapy after >9 years of median follow-up. In contrast, the gains
      from using this approach for stage IB disease are less clear, although data from
      an unplanned subgroup analysis suggest benefit for patients with tumors > or = 4
      cm. Herein, we review the evidence supporting adjuvant therapy in early-stage
      NSCLC patients before discussing key mitigating factors in providing treatment,
      such as stage of disease and the impact of the new seventh edition of the tumor
      node-metastasis classification system. Criteria such as patient age and
      performance status, as well as the value of appropriate chemotherapy selection,
      are highlighted as measures to help guide management. The role of postoperative
      radiotherapy and the future landscape of early-stage NSCLC research are also
      explored; namely, therapeutic strategies exploiting pharmacogenomic and gene
      expression profiling, in an attempt to personalize care, and the integration of
      novel targeted therapies into adjuvant clinical trials.

PMID- 20682609
TI  - Contrast-induced nephropathy and the vascular patient.

PMID- 20682610
TI  - Acute effects of passive smoking on endothelial function.
AB  - Impairment of endothelial functions has been shown to occur after acute and
      chronic exposure to passive smoking (PS), as assessed by flow-mediated dilatation
      (FMD) of the brachial artery. A total of 61 participants, 30 male and 31 female,
      mean ages 26 (18-36) were enrolled in the study. All were clinically well and
      nonsmokers. All participants stayed for 30 minutes in the smoking room. Carbon
      monoxide (CO) level was 7.42 +/- 0.98 ppm (4.71-10.50). Mean carboxyhemoglobin
      (COHb) levels of participants were significantly elevated after PS. Mean FMD was
      18.6% +/- 9% and decreased to 12.4% +/- 7% after PS (P < .001). In the current
      study, with more number of participants at lower CO concentrations (7.42 ppm) and
      with smaller increase in COHb (51%) significant reduction (33%, P < .001) in FMD
      was observed.

PMID- 20682611
TI  - Management of transplant renal artery stenosis.
AB  - End-stage renal disease (ESRD) was universally fatal until dialysis (peritoneal
      and hemodialysis) and renal transplantation were introduced. However, there are
      multiple complications associated with transplantation including transplant renal
      artery stenosis (TRAS). Transplant renal artery stenosis is an important cause of
      premature renal failure, uncontrolled hypertension, and allograft loss. There are
      3 treatment modalities available for TRAS: optimal medical therapy alone,
      percutaneous intervention, and surgical revascularization both with optimal
      medical therapy. Percutaneous transluminal angioplasty (PTA) has now become the
      initial treatment of choice for TRAS. However, there are conflicting data
      regarding the efficacy of PTA, with growing evidence showing lack of significant
      benefit in blood pressure (BP) or renal function in patients undergoing PTA
      versus medical management. However, there have been no randomized control studies
      that have established the superiority of either method. We review the existing
      data and analyze management of TRAS as reported in multiple case series including
      findings from our center.

PMID- 20682612
TI  - Does oral N-acetylcysteine reduce contrast-induced renal injury in patients with
      peripheral arterial disease undergoing peripheral angiography? A randomized
      controlled study.
AB  - The nephroprotective role of N-acetylcysteine (NAC) against contrast-induced
      nephropathy (CIN) in patients undergoing peripheral arterial angiography remains
      unclear. A total of 40 patients undergoing peripheral arterial angiography were
      randomized to receive intravenous (iv) hydration only (group 1) or oral NAC in
      addition to iv hydration (group 2; ISRCTN: 35882618). Primary outcome was
      reduction in the elevation of urinary retinol binding protein (RBP), albumin
      creatinine ratio (ACR), and serum creatinine (serC). Groups 1 and 2 had equivocal
      percentage reduction in RBP and ACR levels from baseline (P = .80 and .30). A
      significant reduction in serC was, however, observed with NAC by third
      postprocedure day (P = .04). One patient in the treatment arm developed CIN
      compared with 3 patients in the control group (P = .33). Equivocal changes in RBP
      and ACR levels by both treatments seem to indicate that either is equally
      effective in affording renal protection.

PMID- 20682613
TI  - Effects of 10 weeks walk training with leg blood flow reduction on carotid
      arterial compliance and muscle size in the elderly adults.
AB  - High-intensity resistance training increases muscle size, but reduces arterial
      compliance. Muscular blood flow reduction (BFR) during low-intensity training has
      been shown to elicit muscle hypertrophy. However, the effect on arterial
      compliance is unknown. We examined the effects of walk training with BFR on
      carotid arterial compliance and muscle size in the elderly adults. Both BFR-walk
      training (BFR-W, n = 13, 66 +/- 1 year) and control-walk training (CON-W, n = 10,
      68 +/- 1 year) groups performed 20 minutes treadmill walking at an exercise
      intensity of 45% of heart rate reserve, 4 days/week for 10 weeks. The BFR-W group
      wore pressure cuffs on both legs during training. Maximum knee joint strength
      (~15%) and MRI-measured thigh muscle cross-sectional area (3%) increased in the
      BFR-W, but not in the CON-W. Carotid arterial compliance improved in both BFR-W
      (50%) and CON-W (59%) groups. Walk training with blood flow reduction can improve
      thigh muscle size/strength as well as carotid arterial compliance, unlike high
      intensity training, in the elderly.

PMID- 20682614
TI  - Effect of glucose and insulin on oxidized low-density lipoprotein phagocytosis by
      human monocytes: a pilot study.
AB  - We assessed the effect of glucose and insulin on human monocytes. Monocytes were
      isolated from 16 healthy obese and 10 lean healthy participants. Insulin
      sensitivity was assessed by euglycemic hyperinsulinemic clamp. Obese participants
      were subdivided into 2 subgroups: insulin sensitive (IS) and insulin resistant
      (IR). Monocyte oxidized low-density lipoprotein (oxLDL) phagocytosis was assessed
      pre and poststimulation in vitro with glucose or insulin. Experiments were
      repeated after incubation with a Na(+)/H(+) exchanger-1 inhibitor ([NHE-1];
      cariporide) or rosiglitazone. Glucose increased oxLDL phagocytosis in all groups
      studied (at 1 or 3 hours incubation; P = .037-.002). Insulin increased oxLDL
      phagocytosis in all groups studied after 1-hour incubation (P = .027-.015) but
      not at 3 hours. Incubation with cariporide attenuated oxLDL phagocytosis except
      in the obese IS group. Rosiglitazone eliminated glucose- and insulin-induced
      increase in oxLDL phagocytosis in all studied groups. Glucose and insulin induce
      oxLDL phagocytosis.

PMID- 20682615
TI  - Effect of epinephrine and insulin resistance on human monocytes obtained from
      lean and obese healthy participants: a pilot study.
AB  - We assessed the effect of epinephrine on human monocytes. Monocytes were isolated
      from 16 healthy obese and 10 lean healthy subjects. Insulin sensitivity was
      assessed by euglycemic hyperinsulinemic clamp. Obese subjects were subdivided
      into 2 sub-groups, insulin sensitive (IS) and insulin resistant (IR). Monocyte
      properties [attachment to laminin 1, migration through laminin 1, oxidized-low
      density lipoprotein (oxLDL) phagocytosis] were assessed pre- and post-stimulation
      in vitro with epinephrine. Experiments were repeated after incubation with a
      Na(+)/H( +) exchanger-1 inhibitor (NHE-1) (cariporide). Epinephrine increased
      monocyte attachment to laminin in lean and obese IR subjects through involvement
      of NHE-1, PKC, NO synthase, NADPH oxidase and actin polymerization. In contrast,
      epinephrine did not affect monocyte migration. Epinephrine increased oxLDL
      phagocytosis in all groups studied. Incubation with cariporide attenuated oxLDL
      phagocytosis. Epinephrine induces monocyte dysfunction which may be atherogenic.

PMID- 20682616
TI  - Are lipid ratios less susceptible to change with systemic inflammation than
      individual lipid components in patients with rheumatoid arthritis?
AB  - Rheumatoid arthritis (RA) associates with excess cardiovascular risk and there is
      a need to assess that risk. However, individual lipid levels may be influenced by
      disease activity and drug use, whereas lipid ratios may be more robust. A cross
      sectional cohort of 400 consecutive patients was used to establish factors that
      influenced individual lipid levels and lipid ratios in RA, using multiple
      regression models. A further longitudinal cohort of 550 patients with RA was used
      to confirm these findings, using generalized estimating equations. Cross
      sectionally, higher C-reactive protein (CRP) levels correlated with lower levels
      of total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), and high
      density lipoprotein-cholesterol ([HDL-C] P <= .015), whereas lipid ratios did not
      correlate with CRP. The findings were broadly replicated in the longitudinal
      data. In summary, the effects of inflammation on individual lipid levels may
      underestimate lipid-associated cardiovascular disease (CVD) risk in RA, thus
      lipid ratios may be more appropriate for CVD risk stratification in RA.

PMID- 20682621
TI  - Avandia panel member may be investigated for possible conflicts of interest.

PMID- 20682623
TI  - Evasion of natural killer cells by influenza virus.
AB  - NK cells are important innate immune effectors during influenza virus infection.
      However, the influenza virus seems able to use several tactics to counter NK cell
      recognition for immune evasion. In this review, we will summarize and discuss
      recent advances regarding the understanding of NK cell evasion mechanisms
      manipulated by the influenza virus to facilitate its rapid replication inside the
      respiratory epithelial cells.

PMID- 20682624
TI  - The C-terminal acidic tail is responsible for the inhibitory effects of HMGB1 on
      efferocytosis.
AB  - HMGB1 was described originally as a nuclear protein involved in DNA binding and
      transcriptional regulation. However, HMGB1 also has an extracellular role as a
      potent mediator of inflammation and can diminish the uptake of apoptotic cells by
      phagocytes, a process called efferocytosis. To explore the mechanism responsible
      for the ability of HMGB1 to inhibit efferocytosis, we examined the role of the C
      terminal acidic tail, a region of HMGB1 that has been shown to participate in
      specific intramolecular interactions. Deletion of the C-terminal tail abrogated
      the ability of HMGB1 to decrease murine macrophage ingestion of apoptotic
      neutrophils and to diminish phagocytosis-induced activation of Erk and Rac-1 in
      macrophages. We found that RAGE plays a major role in efferocytosis, and deletion
      of the C-terminal tail of HMGB1 prevented binding of HMGB1 to RAGE but not to
      other macrophage receptors involved in efferocytosis, such as the alpha(V)beta(3)
      integrin. Whereas HMGB1 decreased ingestion of apoptotic neutrophils
      significantly by alveolar macrophages under in vivo conditions in the lungs of
      mice, this effect was lost when the C-terminal acidic tail was absent from HMGB1.
      These results demonstrate that the HMGB1 C-terminal tail is responsible for the
      inhibitory effects of HMGB1 on phagocytosis of apoptotic neutrophils under in
      vitro and in vivo conditions.

PMID- 20682625
TI  - Tissue-resident mesenchymal stem cells attract peripheral blood neutrophils and
      enhance their inflammatory activity in response to microbial challenge.
AB  - Human MSCs may respond to TLR ligation, and recent research has suggested that
      many tissues contain tissue-specific MSCs, possibly located in periendothelial
      and perivascular regions. At present, the functional consequences of these
      findings are unclear. We hypothesized that tissue-specific MSCs could play an
      instructional role during early phases of bacterial challenge. To investigate
      this hypothesis further, we set up a coculture system of glandular MSCs and
      peripheral blood neutrophils so that we could analyze the cellular interactions
      of these cells in response to LPS challenge. We found that stimulation with
      bacterial endotoxin induced chemokine receptor expression and mobility of MSCs.
      Activated MSCs secreted large amounts of inflammatory cytokines and recruited
      neutrophils in an IL-8- and MIF-dependent manner. Recruited and activated
      neutrophils showed a prolonged lifespan, an increased expression of inflammatory
      chemokines, and an enhanced responsiveness toward subsequent challenge with LPS.
      Our findings demonstrate a complex, functional interaction between tissue
      resident MSCs and peripheral blood neutrophils upon bacterial challenge and
      suggest a role for MSCs in the early phases of pathogen challenge, when classical
      immune cells have not been recruited yet.

PMID- 20682626
TI  - The defensive alliance between neutrophils and NK cells as a novel arm of innate
      immunity.
AB  - The immune system is equipped with a plethora of mechanisms that protect the host
      from the harmful effects of environmental insults. However, the traditional
      "hierarchical" view of the immune response, in which innate, "nonspecific" cells
      are first recruited to the site of damage, before the highly "specific", adaptive
      immune response develops, has been questioned recently. First, the innate
      response is much more specific than recognized previously: indeed, each cell of
      the innate system is not only endowed with an ever-expanding array of germ-line
      encoded receptors, which differentiate between distinct insults, but also is
      modulated continuously by other leukocytes that concomitantly interact with and
      respond to that particular insult. The other reason is that the cells of the
      innate system are instrumental for the adaptive system to accomplish its
      function, as they can also modulate the activity of lymphocytes reciprocally
      during the entire course of the immune response. This complex pattern of
      interactions is illustrated by recent advances on the functions of PMNs, clearly
      showing that unexpectedly, these cells also contribute to the regulation of the
      host immune response by crosstalk with innate and adaptive leukocytes, including
      NK cells. Herein, given the peculiar role of neutrophils and NK cells in
      inflammation, clearance of pathogens/viral-infected cells, and cancer
      immunosurveillance, we summarize the current knowledge about the mechanisms
      whereby neutrophils and NK cells interact and regulate the activities of one
      another, as well as discuss their potential implications involved in the
      pathogenesis of chronic, inflammatory pathologies, infections, and tumors.

PMID- 20682627
TI  - Viral haemorrhagic fevers imported into non-endemic countries: risk assessment
      and management.
AB  - BACKGROUND: Viral haemorrhagic fevers (VHFs) are severe infections capable of
      causing haemorrhagic disease and fatal multi-organ failure. Crimean-Congo,
      Marburg, Ebola and Lassa viruses cause both sporadic cases and large epidemics
      over wide endemic areas. SOURCES OF DATA: Original articles and reviews
      identified by PubMed search and personal reading; European and United States
      national guidance and legislation. World Health Organization information,
      documents and reports. VHFs cause significant morbidity and mortality in their
      endemic areas; they can cause healthcare-related infections, and their broad
      diversity and range are increasingly recognized. AREAS OF CONTROVERSY: There is
      uncertainty about the risks presented by VHFs in non-endemic countries,
      particularly in healthcare environments. Consensus on the best modes of care and
      infection control are only slowly emerging. GROWING POINTS: With increasing
      commerce in rural and low-income areas, VHF outbreaks increasingly expand,
      causing social and economic damage. AREAS TIMELY FOR DEVELOPING RESEARCH: New
      ecologies, viral strains and clinical syndromes are being discovered. There is a
      great need for rapid diagnostic tests and effective antiviral treatments. Vaccine
      development programmes are challenged by multiple viral strains and the need for
      trials in rural communities.

PMID- 20682628
TI  - Genome comparison and phylogenetic analysis of Orientia tsutsugamushi strains.
AB  - Orientia tsutsugamushi (OT) is an obligate intracellular bacterium belonging to
      the family Rickettsiaceae and is the causative agent of scrub typhus, or
      Tsutsugamushi disease. The complete genome sequences of two OT strains (Boryong
      and Ikeda) have recently been determined. In the present study, we performed a
      fine genome sequence comparison of these strains. Our results indicate that
      although the core gene set of the family Rickettsiaceae is highly conserved
      between the two strains, a common set of repetitive sequences have been
      explosively amplified in both genomes. These amplified repetitive sequences have
      induced extensive genome shuffling and duplications and deletions of many genes.
      On the basis of the results of the genome sequence comparison, we selected 11
      housekeeping genes and carried out multilocus sequence analysis of OT strains
      using the nucleotide sequences of these genes. This analysis revealed for the
      first time the phylogenetic relationships of representative OT strains.
      Furthermore, the results suggest the presence of an OT lineage with higher
      potential for virulence, which may explain the clinical and epidemiological
      differences between 'classic' and 'new' types of Tsutsugamushi disease in Japan.

PMID- 20682629
TI  - Azygos flap as a novel method for superior vena cava reconstruction.
AB  - In the surgical treatment of lung cancers invading the superior vena cava (SVC),
      primary closure is preferred for reconstruction when the resected area is small,
      but the repaired vessel can become constricted. A novel method for SVC repair
      with azygos flap, which is a longitudinally opened azygos arch, is a facile and
      effective treatment, and may prevent a reduction in the lumen if the area of
      tumor invasion is small and close to the azygos arch. When the azygos arch is not
      invaded by the tumor, this procedure should therefore be considered as one
      alternative method for SVC reconstruction.

PMID- 20682630
TI  - Modified ultrafiltration attenuates pulmonary-derived inflammatory mediators in
      response to cardiopulmonary bypass.
AB  - Cardiopulmonary bypass (CPB) stimulates systemic and pulmonary inflammation.
      Modified ultrafiltration (MUF) mitigates deleterious CPB effects by unclear
      mechanisms. We evaluated pulmonary inflammation in piglets undergoing CPB
      followed by MUF. Twenty-four piglets underwent 60 min of hypothermic CPB. MUF
      subjects (n=12) underwent hemoconcentration postCPB to the target hematocrit.
      Pulmonary vascular resistance (PVR), proinflammatory cytokine concentrations, and
      transpulmonary thromboxane gradients were determined at baseline, following CPB,
      and at end of the study (EOS) in MUF and control (n=12) groups. PVR significantly
      increased postCPB in both groups but decreased after MUF. MUF and control groups
      were similar in regards to systemic cytokine concentrations. Bronchoalveolar
      lavage concentrations of IL-6 and IL-8 significantly increased in controls
      throughout the study. Alveolar IL-6 and IL-8 were unchanged at EOS in MUF
      subjects, and IL-6 concentrations were significantly less than controls at EOS
      (P=0.015). Similarly, transpulmonary thromboxane gradient was significantly less
      at EOS in MUF subjects compared with controls (P=0.04). MUF removed circulating
      inflammatory mediators, lessened pulmonary hypertension, and reduced pulmonary
      derived inflammatory markers, providing further evidence that MUF ameliorates
      pulmonary-based inflammation. These findings lend insight into mechanisms behind
      salutary clinical benefits of MUF after CPB.

PMID- 20682631
TI  - Can transit-time flow measurement improve graft patency and clinical outcome in
      patients undergoing coronary artery bypass grafting?
AB  - A best evidence topic in cardiac surgery was written according to a structured
      protocol. The question addressed was if transit-time flow measurement (TTFM) can
      improve graft patency and clinical outcome in patients undergoing coronary
      surgery. Altogether 102 papers were found using the reported search, of which 10
      represented the best evidence to answer the clinical question. The authors,
      journal, date and country of publication, patient group studied, study type,
      relevant outcomes and results of these papers are tabulated. The papers
      considered for the analysis focus attention on three major topics: intraoperative
      graft verification with the aim of improving immediate graft patency; predictive
      power of early- and mid-term graft patency and clinical outcome. Among TTFM
      parameters, according to different authors, mean graft flow is set at 10 or 15
      ml/min; pulsatility index is set at three or five; insufficiency ratio is set by
      3 or 4%. We conclude that TTFM is a reliable method to verify intraoperative
      graft patency. There is some evidence that checking graft patency
      intraoperatively may improve mid-term outcomes.

PMID- 20682632
TI  - Universal screening detects two-times more thyroid disorders in early pregnancy
      than targeted high-risk case finding.
AB  - OBJECTIVE: Screening of thyroid disorders in pregnancy has been controversial.
      Recent recommendations favour targeted high-risk case finding, though this
      approach may miss a significant number of those affected. We aimed to assess the
      prevalence of accepted high-risk criteria in women with autoimmune thyroiditis
      and/or hypothyroidism detected from universal screening in an iodine-sufficient
      population. DESIGN: In 400 non-selected women in the 9-11th gestational week,
      thyroid-related tests were performed, and those with abnormalities were offered
      consultation. METHODS: TSH was determined by IRMA, and the upper cut-off value
      for screening was set at 3.5 mIU/l. For free thyroxine (FT(4)) and
      thyroperoxidase antibodies (TPO-Ab), RIAs were used, with cut-offs of <10 pmol/l
      and >50 IU/ml respectively. Endocrinological consultation included Doppler
      ultrasonography and was aimed to confirm autoimmune thyroiditis and/or
      hypothyroidism. The prevalence of consensus high-risk criteria was assessed.
      RESULTS: Among the 400 women, 65 (16.3%) had >=1 abnormality: higher TSH was
      found in 10.3%, lower FT(4) in 2% and positive TPO-Ab in 8.3%. Fifty-one women
      were examined and followed up. Levo-T(4) treatment was initiated in 49 women for
      autoimmune thyroiditis (in 42), hypothyroidism (in 34) or both (in 27). Only 22
      (45%) of 49 treated women fulfilled >=1 high-risk criterion: most commonly family
      history (31%), history of miscarriage or preterm delivery (14%) and personal
      history (8%). CONCLUSIONS: Over half (55%) of pregnant women with abnormalities
      suggestive of autoimmune thyroiditis and/or hypothyroidism would be missed if
      only those with high-risk criteria were examined. A more extensive screening of
      thyroid autoimmunity and dysfunction seems warranted.

PMID- 20682633
TI  - Growth-restricted preterm newborns are predisposed to functional adrenal
      hyperandrogenism in adult life.
AB  - BACKGROUND: The long-term effects of perinatal growth and corticosteroid exposure
      on adrenal steroid concentrations in adults born very preterm are uncertain.
      OBJECTIVES: To examine the effect of birth weight, early postnatal growth, and
      pre- and postnatal corticosteroid administration on serum adrenal steroids in 19
      year-old subjects born very preterm. DESIGN AND METHODS: Subjects born before 32
      weeks of gestation in The Netherlands participating in the Project on Preterm and
      Small for Gestational Age Infants (POPS) were investigated at 19 years of age.
      Serum cortisol, DHEA sulfate (DHEAS), and androstenedione (Adione) concentrations
      were measured in 393 out of 676 eligible subjects, compared with controls, and
      associated with perinatal growth and pre- and postnatal corticosteroids
      administration using multiple linear regression analyses. RESULTS: Serum DHEAS
      and Adione in men and women were higher than in controls. In the multiple
      regression analyses, birth weight SDS showed a statistically significant negative
      association with serum DHEAS concentrations in women (beta: -0.865, 95%
      confidence interval (CI): -1.254 to -0.476) and in men (beta: -0.758, 95% CI: 
      1.247 to -0.268) and with serum Adione concentrations in women (beta: -0.337, 95%
      CI: -0.593 to -0.082). Early postnatal weight gain showed no association with any
      of measured adrenal markers. In women, serum Adione was associated with postnatal
      dexamethasone exposure (beta: 0.932, 95% CI: 0.022 - 1.843). CONCLUSIONS: Young
      adults born very preterm show elevated adrenal androgens, particularly when born
      small for gestational age. Postnatal corticosteroid administration is positively
      associated with serum Adione in young women.

PMID- 20682634
TI  - Impact of integration of clinical and outpatient units on cancer patient
      satisfaction.
AB  - OBJECTIVE: There is an ongoing drive to measure and improve quality of care.
      Donabedians' quality framework with structure, process and outcome domains
      provides a useful hold to examine quality of care. The aim of this study was to
      address the effect of an intervention in hospital structure (integration of three
      units into one) with the purpose of improving processes (increase meeting,
      cooperation and communication between professionals and patients) and its effect
      on the outcome (cancer patient satisfaction). DESIGN: Pre-test-post-test.
      SETTING: University Medical Center Utrecht, The Netherlands, Department of
      Medical Oncology. PARTICIPANTS: Cancer patients (n = 174, n = 97). INTERVENTIONS:
      Physical integration by bringing separately located units (outpatient clinic, day
      care clinic, clinical ward) together in one wing of the hospital and adjustments
      in communication and coordination structures. MAIN OUTCOME MEASURE: Patient
      satisfaction questionnaire. RESULTS: Satisfaction with care improved for six
      scales (27%) after integration. Effect sizes (ESs) ranged from 0.36 to 0.80,
      indicating a small to moderate effect. The most important improvement was found
      at the day-care clinic on aspects like 'the degree in which the nurses were
      informed about a patients situation', 'privacy', 'interior design', 'quality of
      hospital equipment', 'sanitary supplies' and 'waiting periods'. With regard to
      continuity and coordination of care, satisfaction increased for five items (28%
      of items concerning continuity and coordination of care). ESs ranged from 0.42 to
      0.75. CONCLUSIONS: Integration of three oncology units into one unit had a
      positive impact on care delivery processes and resulted in improved patient
      satisfaction concerning care and treatment.

PMID- 20682635
TI  - Decoupling diffusional from dimensional control of signaling in 3D culture
      reveals a role for myosin in tubulogenesis.
AB  - We present a novel microfabricated platform to culture cells within arrays of
      micrometer-scale three-dimensional (3D) extracellular matrix scaffolds
      (microgels). These microscale cultures eliminate diffusion barriers that are
      intrinsic to traditional 3D culture systems (macrogels) and enable uniform
      cytokine stimulation of the entire culture population, as well as allow
      immunolabeling, imaging and population-based biochemical assays across the
      relatively coplanar microgels. Examining early signaling associated with
      hepatocyte growth factor (HGF)-mediated scattering and tubulogenesis of MDCK
      cells revealed that 3D culture modulates cellular responses both through
      dimensionality and altered stimulation rates. Comparing responses in 2D culture,
      microgels and macrogels demonstrated that HGF-induced ERK signaling was driven by
      the dynamics of stimulation and not by whether cells were in a 2D or 3D
      environment, and that this ERK signaling was equally important for HGF-induced
      cell scattering on 2D substrates and tubulogenesis in 3D. By contrast, we
      discovered a specific HGF-induced increase in myosin expression leading to
      sustained downregulation of myosin activity that occurred only within 3D contexts
      and was required for 3D tubulogenesis but not 2D scattering. Interestingly,
      although absent in cells on collagen-coated plates, downregulation of myosin
      activity also occurred for cells on collagen gels, but was transient and mediated
      by a combination of myosin dephosphorylation and enhanced myosin expression.
      Furthermore, upregulating myosin activity via siRNA targeted to a myosin
      phosphatase did not attenuate scattering in 2D but did inhibit tubulogenesis in
      3D. Together, these results demonstrate that cellular responses to soluble cues
      in 3D culture are regulated by both rates of stimulation and by matrix
      dimensionality, and highlight the importance of decoupling these effects to
      identify early signals relevant to cellular function in 3D environments.

PMID- 20682636
TI  - Elevated expression of protein kinase C delta induces cell scattering upon serum
      deprivation.
AB  - Tumor metastasis might be evoked in response to microenvironmental stress, such
      as a shortage of oxygen. Although the cellular response to hypoxia has been well
      established, we know little about how tumors adapt themselves to deprivation of
      growth factor. Protein kinase Cdelta (PKCdelta), a stress-sensitive protein
      kinase, has been implicated in tumor progression. In this study, we demonstrate
      that elevated expression of PKCdelta in Madin-Darby canine kidney cells induces a
      scatter response upon serum starvation, a condition that mimics growth-factor
      deprivation. Serum starvation stimulates the catalytic activity and Y311
      phosphorylation of PKCdelta through reactive oxygen species (ROS) and the Src
      family kinases. Mutation of PKCdelta at Y311 and Y322, both of which are
      phosphorylation sites for Src, impairs its activation and ability to promote cell
      scattering upon serum deprivation. Once activated by ROS, PKCdelta itself
      activates ROS production at least partially through NADPH oxidase. In addition,
      the c-Jun N-terminal kinase is identified as a crucial downstream mediator of ROS
      and PKCdelta for induction of cell scattering upon serum deprivation. We
      demonstrate that the C1B domain of PKCdelta is essential not only for its
      localization at the Golgi complex, but also for its activation and ability to
      induce cell scattering upon serum deprivation. Finally, depletion of PKCdelta in
      human bladder carcinoma T24 cells restores their cell-cell contacts, which
      thereby reverses a scattered growth pattern to an epithelial-like growth pattern.
      Collectively, our results suggest that elevated expression of PKCdelta might
      facilitate the scattering of cells in order to escape stress induced by growth
      factor deprivation.

PMID- 20682637
TI  - Basal body movements orchestrate membrane organelle division and cell
      morphogenesis in Trypanosoma brucei.
AB  - The defined shape and single-copy organelles of Trypanosoma brucei mean that it
      provides an excellent model in which to study how duplication and segregation of
      organelles is interfaced with morphogenesis of overall cell shape and form. The
      centriole or basal body of eukaryotic cells is often seen to be at the centre of
      such processes. We have used a combination of electron microscopy and electron
      tomography techniques to provide a detailed three-dimensional view of duplication
      of the basal body in trypanosomes. We show that the basal body duplication and
      maturation cycle exerts an influence on the intimately associated flagellar
      pocket membrane system that is the portal for secretion and uptake from this
      cell. At the start of the cell cycle, a probasal body is positioned anterior to
      the basal body of the existing flagellum. At the G1-S transition, the probasal
      body matures, elongates and invades the pre-existing flagellar pocket to form the
      new flagellar axoneme. The new basal body undergoes a spectacular anti-clockwise
      rotation around the old flagellum, while its short new axoneme is associated with
      the pre-existing flagellar pocket. This rotation and subsequent posterior
      movements results in division of the flagellar pocket and ultimately sets
      parameters for subsequent daughter cell morphogenesis.

PMID- 20682638
TI  - Impaired tissue growth is mediated by checkpoint kinase 1 (CHK1) in the
      integrated stress response.
AB  - The integrated stress response (ISR) protects cells from numerous forms of stress
      and is involved in the growth of solid tumours; however, it is unclear how the
      ISR acts on cellular proliferation. We have developed a model of ISR signalling
      with which to study its effects on tissue growth. Overexpression of the ISR
      kinase PERK resulted in a striking atrophic eye phenotype in Drosophila
      melanogaster that could be rescued by co-expressing the eIF2alpha phosphatase
      GADD34. A genetic screen of 3000 transposon insertions identified grapes, the
      gene that encodes the Drosophila orthologue of checkpoint kinase 1 (CHK1).
      Knockdown of grapes by RNAi rescued eye development despite ongoing PERK
      activation. In mammalian cells, CHK1 was activated by agents that induce ER
      stress, which resulted in a G2 cell cycle delay. PERK was both necessary and
      sufficient for CHK1 activation. These findings indicate that non-genotoxic
      misfolded protein stress accesses DNA-damage-induced cell cycle checkpoints to
      couple the ISR to cell cycle arrest.

PMID- 20682639
TI  - Mobility of G proteins is heterogeneous and polarized during chemotaxis.
AB  - The interaction of G-protein-coupled receptors with G proteins is a key event in
      transmembrane signal transduction that leads to vital decision-making by the
      cell. Here, we applied single-molecule epifluorescence microscopy to study the
      mobility of both the Gbetagamma and the Galpha2 subunits of the G protein
      heterotrimer in comparison with the cAMP receptor responsible for chemotactic
      signaling in Dictyostelium discoideum. Our experimental results suggest that
      approximately 30% of the G protein heterotrimers exist in receptor-precoupled
      complexes. Upon stimulation in a chemotactic gradient, this complex dissociates,
      subsequently leading to a linear diffusion and collision amplification of the
      external signal. We further found that Gbetagamma was partially immobilized and
      confined in an agonist-, F-actin- and Galpha2-dependent fashion. This led to the
      hypothesis that functional nanometric domains exist in the plasma membrane, which
      locally restrict the activation signal, and in turn, lead to faithful and
      efficient chemotactic signaling.

PMID- 20682640
TI  - TIMP3: a physiological regulator of adult myogenesis.
AB  - Myogenic differentiation in adult muscle is normally suppressed and can be
      activated by myogenic cues in a subset of activated satellite cells. The switch
      mechanism that turns myogenesis on and off is not defined. In the present study,
      we demonstrate that tissue inhibitor of metalloproteinase 3 (TIMP3), the
      endogenous inhibitor of TNFalpha-converting enzyme (TACE), acts as an on-off
      switch for myogenic differentiation by regulating autocrine TNFalpha release. We
      observed that constitutively expressed TIMP3 is transiently downregulated in the
      satellite cells of regenerating mouse hindlimb muscles and differentiating C2C12
      myoblasts. In C2C12 myoblasts, perturbing TIMP3 downregulation by overexpressing
      TIMP3 blocks TNFalpha release, p38 MAPK activation, myogenic gene expression and
      myotube formation. TNFalpha supplementation at a physiological concentration
      rescues myoblast differentiation. Similarly, in the regenerating soleus,
      overexpression of TIMP3 impairs release of TNFalpha and myogenic gene expression,
      and delays the formation of new fibers. In addition, downregulation of TIMP3 is
      mediated by the myogenesis-promoting microRNA miR-206. Thus, TIMP3 is a
      physiological regulator of myogenic differentiation.

PMID- 20682641
TI  - Calcimimetic R-568 effects on activity of R990G polymorphism of calcium-sensing
      receptor.
AB  - Previous studies have demonstrated a gain-of-function of the calcium-sensing
      receptor (CASR) gene R990G polymorphism. In this study, activation of the R990G
      CASR stably transfected in HEK-293 (HEK-990G) cells compared with that of the
      common variant (HEK-wild-type (WT)) by increasing concentrations of CaCl(2) or
      calcimimetic R-568 caused significantly higher intracellular free calcium
      concentration ([Ca(2+)](i)) and lower Ca-EC(50). Moreover, the [Ca(2+)](i)
      oscillation percentage was higher with a larger sinusoidal pattern in HEK-990G. R
      568 induced a shift of the oscillatory events from 4 to 2  mmol/l extracellular
      calcium concentration in HEK-990G cells and increased the sinusoidal oscillation
      percentage in comparison with HEK-WT. Preincubation with thapsigargin or
      phospholipase C inhibitors completely prevented oscillations in both cell lines,
      consistent with the involvement of the inositol trisphosphate pathway, while
      protein kinase C inhibitor prevented oscillations in HEK-WT cells only. Finally,
      CaCl(2) and R-568 caused a significant increase in p44/42 extracellular signaling
      regulated kinase phosphorylation, with the mean Ca-EC(50) values being
      significantly lower in HEK-990G. Our findings demonstrated that the 990G allele
      is associated with high sensitivity to R-568, which provided new evidence for
      differences in CASR signaling.

PMID- 20682642
TI  - Expanding roles of NUCB2/nesfatin-1 in neuroendocrine regulation.
AB  - Nesfatin-1 was originally identified as a hypothalamic neuropeptide, derived from
      the precursor NEFA (for DNA binding/EF-hand/acidic protein)/nucleobindin 2
      (NUCB2), with the ability to suppress food intake, acting in a leptin-independent
      manner. Departing from this seminal finding, the patterns of expression of
      NUCB2/nesfatin-1 have been thoroughly characterized in different hypothalamic
      nuclei and brain areas with proven roles in energy homeostasis, and its potential
      interactions with other key neuropeptide regulators of appetite have been
      documented. Intriguingly, recent experimental evidence suggests that
      NUCB2/nesfatin-1 is also expressed in peripheral tissues with relevant metabolic
      functions, such as the pancreas, the adipose, and the gut. In addition, evidence
      is mounting that nesfatin signaling may participate in adaptative responses and
      in the control of body functions gated by the state of energy reserves, such as
      puberty onset. Altogether, these observations have broadened our perception of
      the biological profile of nesfatin-1 that, rather than a simple anorectic signal
      in the hypothalamus, might operate at different tissues as an integral regulator
      of energy homeostasis and closely related neuroendocrine functions.

PMID- 20682643
TI  - Combinations of DNA methyltransferase and histone deacetylase inhibitors induce
      DNA damage in small cell lung cancer cells: correlation of resistance with IFN
      stimulated gene expression.
AB  - Because epigenetic inhibitors can reduce cancer cell proliferation, we tested the
      hypothesis that concurrent inhibition of histone acetylation and DNA methylation
      could synergistically reduce the viability of small cell lung cancer (SCLC)
      cells. Sub-IC(50) concentrations of the DNA methyltransferase (DNMT) inhibitor
      decitabine (5-AZA-dC) and the histone deacetylase (HDAC) inhibitors (LBH589 or
      MGCD0103) synergistically reduced the proliferation of five of nine SCLC cell
      lines. Loss of viability of sensitive SCLC cells did not correlate with the
      inhibition of either DNMT1 or HDACs, suggesting nonepigenetic mechanisms for
      synergy between these two classes of epigenetic modulators. Because combinations
      of 5-AZA-dC and HDAC inhibitors had marginal effects on the apoptosis index,
      Comet assay was undertaken to assess DNA damage. MGCD0103 and 5AZA-dC cotreatment
      augmented DNA damage in SCLC cells, resulting in increased tail length and moment
      in Comet assays by 24 hours in sensitive cell lines (P < 0.01). Consistent with
      augmented DNA damage, combination of a DNMT and HDAC inhibitor markedly increased
      the levels of phospho-H2A.X in sensitive cells but not in resistant ones.
      Comparison of basal gene expression between resistant and sensitive cells
      identified markedly higher basal expression of IFN-stimulated genes in the
      resistant cell lines, suggesting that IFN-stimulated gene expression may
      determine SCLC cell sensitivity to epigenetic modulators or other DNA damaging
      agents.

PMID- 20682645
TI  - Lipoxin A4 and its analogue suppress the tumor growth of transplanted H22 in
      mice: the role of antiangiogenesis.
AB  - Tumor angiogenesis plays an essential role in carcinogenesis, cancer progression,
      and metastasis. Some studies indicate that lipoxins, endogenous anti-inflammatory
      lipid mediators, might be involved in tumor angiogenesis; however, the governing
      mechanisms are still unknown. In the present study, we examined the effects of
      exogenous lipoxin A(4) (LXA(4)) in mouse hepatocarcinoma cell line (H22) and H22
      bearing mice model. It was found that in H22 cells, LXA(4) inhibited the
      production of vascular endothelial growth factor and reduced hypoxia-inducible
      factor-1 alpha level. In addition, its analogue, BML-111, blocked the expression
      of vascular endothelial growth factor in serum and tumor sections from H22
      bearing mice. H&E staining and immunostaining with antibodies against CD34
      revealed that BML-111 suppressed tumor-related angiogenesis in vivo, but LXA(4)
      could not influence the proliferation of primary cultured human umbilical vein
      endothelial cells. The tumor growth was also inhibited by BML-111. We also found
      that BML-111 enhanced the in situ apoptosis while inhibiting macrophage
      infiltration in tumor tissue. The results provide new evidence that LXA(4)
      suppresses the growth of transplanted H22 tumor in mice through inhibiting tumor
      related angiogenesis.

PMID- 20682644
TI  - Expression of ABCG2 (BCRP) is regulated by Nrf2 in cancer cells that confers side
      population and chemoresistance phenotype.
AB  - ATP-binding cassette, subfamily G, member 2 (ABCG2) is expressed in both normal
      and cancer cells and plays a crucial role in side population (SP) formation and
      efflux of xenobiotics and drugs. Nrf2, a redox-sensing transcription factor, on
      constitutive activation in non-small-cell lung cancer cells upregulates a wide
      spectrum of genes involved in redox balance, glutathione metabolism, and drug
      detoxification, which contribute to chemoresistance and tumorigenicity. This
      study examined the mechanism underlying Nrf2-dependent expression of ABCG2 and
      its role in the multidrug resistance phenotype. In silico analysis of the 5'
      promoter flanking region of ABCG2 identified an antioxidant response element
      (ARE) at -431 to -420 bp. A detailed promoter analysis using luciferase reporter
      assays showed that ARE at -431 to -420 bp is critical for the Nrf2-mediated
      expression in lung cancer cells. Electrophoretic mobility shift assays and
      chromatin immunoprecipitation assays revealed that Nrf2 interacts with the ABCG2
      ARE element at -431 to -420 bp in vitro and in vivo. Disruption of Nrf2
      expression in lung and prostate cancer cells, by short hairpin RNA, attenuated
      the expression of ABCG2 transcript and protein, and dramatically reduced the SP
      fraction in Nrf2-depleted cancer cells. Moreover, depleted levels of ABCG2 in
      these Nrf2 knockdown cells sensitized them to mitoxantrone and topotecan, two
      chemotherapy drugs detoxified mainly by ABCG2. As expected, overexpression of
      Nrf2 cDNA in lung epithelial cells led to an increase in ABCG2 expression and a 2
      fold higher SP fraction. Thus, Nrf2-mediated regulation of ABCG2 expression
      maintains the SP fraction and confers chemoresistance.

PMID- 20682646
TI  - Overexpression of GRIM-19 in cancer cells suppresses STAT3-mediated signal
      transduction and cancer growth.
AB  - Constitutive activation of signal transducer and activator of transcription 3
      (STAT3) is common in many human and murine cancer cells, and its activation leads
      to cellular transformation. STAT3 pathway inhibitors have been reported to
      suppress cancer growth. To investigate the antitumor effects of inhibiting the
      STAT3-mediated signaling cascade in the cancer microenvironment, using a
      molecular-targeting approach, we focused on the gene associated with retinoid-IFN
      induced mortality 19 (GRIM-19). GRIM-19 has been reported to interact physically
      with STAT3 and inhibit STAT3-dependent signal transduction. We used the nona
      arginine (R9)-protein transduction domain (R9-PTD) as a protein carrier to induce
      high levels of GRIM-19 expression in vitro and in vivo. We generated an R9-PTD
      containing GRIM-19 fusion protein (rR9-GRIM19) and successfully induced
      overexpression in the cytoplasm of cancer cells. Analysis of the expression of
      downstream molecules of STAT3 confirmed that in vitro rR9-GRIM19 treatment of
      constitutively activated STAT3 (STAT3c) cancer cells significantly reduced STAT3
      dependent transcription. Moreover, intratumoral injections of rR9-GRIM19 in
      STAT3c cancer-bearing mice significantly suppressed tumor growth. These results
      suggest that intratumoral injections of rR9-GRIM19 have potential as a novel
      anticancer therapy in STAT3c cancer due to their ability to inhibit STAT3
      mediated signal transduction without major systemic side effects.

PMID- 20682647
TI  - Tyrosine phosphatase inhibitor-3 sensitizes melanoma and colon cancer to
      biotherapeutics and chemotherapeutics.
AB  - Drug resistance is a major obstacle in cancer treatments and diminishes the
      clinical efficacy of biological, cytotoxic, or targeted therapeutics. Being an
      antiapoptotic mediator of chemoresistance in breast and lung cancer cells, MKP1
      phosphatase might be targeted for overcoming chemoresistance and improving
      therapeutic efficacy. In this work, tyrosine phosphatase inhibitor-3 (TPI-3) was
      identified as a novel small molecule inhibitor of MKP1 and was capable of
      sensitizing tumors to bio- and chemotherapeutics in mice as a tolerated oral
      agent. Effective against recombinant MKP1, TPI-3 selectively increased MKP1
      phosphosubstrates in Jurkat cells and induced cell death via apoptosis at
      nanomolar concentrations. TPI-3 also increased MKP1 phosphosubstrates in WM9
      human melanoma cells and synergized with biotherapeutic IFN alpha 2b in the
      growth inhibition of melanoma cells in vitro (combination index, <1). WM9
      xenografts unresponsive to individual agents were significantly inhibited (62%, P
      = 0.001) in mice by a tolerated combination of oral TPI-3 (10 mg/kg, 5 d/wk) and
      IFN alpha 2b. MKP1 expression was detected in human melanoma cell lines and
      tissue samples at levels up to six times higher than those in normal or
      nonmalignant melanocytes. TPI-3 also interacted positively with
      chemotherapeutics, 5-fluorouracil/leucovorin, against MC-26 colon cancer cells in
      vitro and in mice. Altogether, our data show the preclinical activities of TPI-3
      in overcoming cancer resistance to bio- and chemotherapeutics, implicate MKP1 as
      a drug-resistant molecule in melanoma, and support the targeting of MKP1 for
      improving cancer therapeutic efficacy.

PMID- 20682649
TI  - Phase II trial to evaluate gemcitabine and etoposide for locally advanced or
      metastatic pancreatic cancer.
AB  - Prior studies suggest that tumor cell lines harboring RAS mutations display
      remarkable sensitivity to gemcitabine and etoposide. In a phase II clinical trial
      of patients with locally advanced or metastatic pancreatic cancer, we evaluated
      the response rate to a combination of these drugs. Forty chemo-naive patients
      with nonresectable and histologically confirmed pancreatic cancer were accrued.
      Patients received gemcitabine 1,000 mg/m(2) (days 1 and 8) and etoposide 80
      mg/m(2) (days 8, 9, and 10; 21-day cycle). The primary end point was radiological
      response rate. Secondary objectives were determination of overall survival,
      response duration (time to progression), quality of life, toxicity, and CA 19-9
      biomarker response. In 35 evaluable patients, 10 exhibited a radiological partial
      response and 12 had stable disease in response to treatment. Twenty patients
      exhibited a >20% decrease in CA 19-9 biomarker levels. Median overall survival
      was 6.7 months for all patients (40) and 7.2 months for evaluable patients (35).
      Notably, four patients survived for longer than 1 year, with two patients
      surviving for more than 2 years. Median time to progression for evaluable
      patients was 3.1 months. The median overall survival for locally advanced
      patients was 8.8 months and 6.75 months for metastatic patients. One-year
      survival was 10% for all patients and 11.4% for evaluable patients. Quality of
      life improved in 12 patients and remained stable in 3 of the evaluable patients.
      The primary dose-limiting toxicities were hematologic toxicity and fatigue. These
      results show that the gemcitabine and etoposide combination is generally well
      tolerated and exhibits a response rate similar to other published studies.

PMID- 20682650
TI  - Gamma-tocotrienol promotes TRAIL-induced apoptosis through reactive oxygen
      species/extracellular signal-regulated kinase/p53-mediated upregulation of death
      receptors.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a member of the
      tumor necrosis factor superfamily, is in clinical trials for cancer therapy, but
      its anticancer potential is limited by the development of resistance. We
      investigated the ability of tocotrienol (T3), an unsaturated vitamin E present in
      palm oil, rice bran, barley, oats, and wheat germ, to sensitize tumor cells to
      TRAIL. Results from esterase staining, colony formation, caspase activation, and
      sub-G(1) cell cycle arrest revealed that gamma-T3 can sensitize human colon
      cancer cells to TRAIL. When examined for the mechanism, we found that gamma-T3
      significantly downregulated the expression of antiapoptotic proteins (c-IAP2 and
      Bcl-xL). We also found that gamma-T3, but not tocopherol, induced the expression
      of the TRAIL receptors death receptor (DR)-4 and DR5. This induction was not cell
      type specific, as upregulation was also found in pancreatic, kidney, and leukemic
      cells. Upregulation of DRs by gamma-T3 required the production of reactive oxygen
      species (ROS), and sequestering of ROS abolished both upregulation of the
      receptors and potentiation of TRAIL-induced apoptosis. Induction of DRs by gamma
      T3 also required activation of extracellular signal-regulated kinase 1 (ERK1), as
      silencing of ERK1 by specific siRNA abrogated the upregulation of TRAIL
      receptors. Further, induction of DRs by gamma-T3 required the expression of p53
      and Bax, as no induction of the receptors was found in colon cancer cells with
      deletion of these genes. Overall, our results show that gamma-T3 sensitizes tumor
      cells to TRAIL by upregulating DRs through the ROS/ERK/p53 pathway and by
      downregulating cell survival proteins.

PMID- 20682651
TI  - Serine proteases in histone deacetylase inhibitor-induced apoptosis.

PMID- 20682652
TI  - Decreased survival of human breast cancer cells expressing HER2/neu on in vitro
      incubation with an anti-HER2/neu antibody fused to C5a or C5a desArg.
AB  - Treatment of human epidermal growth factor receptor 2 (HER2/neu)-expressing
      breast cancer patients with a monoclonal antibody (mAb) directed against HER2/neu
      improves the outcome of chemotherapy. In cases in which remission is observed,
      antibody-dependent cell-mediated cytotoxicity (ADCC) seems to be one of the main
      mechanisms of anti-HER2/neu mAb action, implicating Fc gamma receptors (Fc gamma
      Rs) in this tumoricidal activity. In vitro and in vivo studies have revealed that
      anti-HER2/neu-mediated ADCC is mainly accomplished by polymorphonuclear
      granulocytes (PMN). C5a, a cleavage product of the complement component C5,
      modulates Fc gamma R expression via upregulation of activating and downregulation
      of inhibitory Fc gamma Rs. C5a also recruits PMNs to sites of inflammation and
      increases PMN survival. To enhance the recruitment and activation of C5a receptor
      bearing cells into the tumor microenvironment, we developed antibody fusion
      proteins composed of a human IgG3 anti-HER2/neu antibody genetically fused to C5a
      [anti-HER2/neu IgG3-(C5a)] or to its derivative, C5a(desArg) [anti-HER2/neu IgG3
      (C5a(desArg))]. Both fusion proteins were expressed, properly assembled, and
      secreted by murine myeloma cells, and displayed chemotactic activity on human
      PMN. Under comparable conditions, anti-HER2/neu IgG3-(C5a(desArg)) increased the
      survival of PMN more efficiently than anti-HER2/neu IgG3-(C5a) or C5a(desArg).
      Surprisingly, incubation of the fusion proteins with breast cancer cells that
      overexpress HER2/neu (SK-BR-3) induced cell death at a dose at which the anti
      HER2/neu IgG3 antibody was innocuous. In the presence of human peripheral blood
      leukocytes as effector cells, both fusion proteins induced tumor cell death more
      efficiently than anti-HER2/neu IgG3. These data suggest that anti-HER2/neu IgG3
      (C5a) and anti-HER2/neu IgG3-(C5a(desArg)) fusion proteins possess novel
      properties that could be useful in cancer immunotherapy.

PMID- 20682653
TI  - Converging evidence for efficacy from parallel EphB4-targeted approaches in
      ovarian carcinoma.
AB  - EphB4 is a transmembrane receptor tyrosine kinase that plays an important role in
      neural plasticity and angiogenesis. EphB4 is overexpressed in ovarian cancer and
      is predictive of poor clinical outcome. However, the biological significance of
      EphB4 in ovarian cancer is not known and is the focus of the current study. Here,
      we examined the biological effects of two different methods of EphB4 targeting (a
      novel monoclonal antibody, EphB4-131 or siRNA) using several ovarian cancer
      models. EphB4 gene silencing significantly increased tumor cell apoptosis and
      decreased migration (P < 0.001) and invasion (P < 0.001). Compared with controls,
      EphB4 siRNA-1,2-dioleoyl-sn-glycero-3-phosphatidylcholine alone significantly
      reduced tumor growth in the A2780-cp20 (48%, P < 0.05) and IGROV-af1 (61%, P <
      0.05) models. Combination therapy with EphB4 siRNA-1,2-dioleoyl-sn-glycero-3
      phosphatidylcholine and docetaxel resulted in the greatest reduction in tumor
      weight in both A2780-cp20 and IGROV-af1 models (89-95% reduction versus controls;
      P < 0.05 for both groups). The EphB4-131 antibody, which reduced EphB4 protein
      levels, decreased tumor growth by 80% to 83% (P < 0.01 for both models) in A2780
      cp20 and IGROV-af1 models. The combination of EphB4-131 and docetaxel resulted in
      the greatest tumor reduction in both A2780-cp20 and IGROV-af1 models (94-98%
      reduction versus controls; P < 0.05 for both groups). Compared with controls,
      EphB4 targeting resulted in reduced tumor angiogenesis (P < 0.001), proliferation
      (P < 0.001), and increased tumor cell apoptosis (P < 0.001), which likely occur
      through modulation of phosphoinositide 3-kinase signaling. Collectively, these
      data identify EphB4 as a valuable therapeutic target in ovarian cancer and offer
      two new strategies for further development.

PMID- 20682654
TI  - Epidermal growth factor receptor-targeted radioimmunotherapy of human head and
      neck cancer xenografts using 90Y-labeled fully human antibody panitumumab.
AB  - Panitumumab (ABX-EGF or Vectibix), the first fully human monoclonal antibody
      targeting epidermal growth factor receptor (EGFR), was approved by the Food and
      Drug Administration for treatment of patients with metastatic colorectal cancer.
      Here, we report for the first time the radioimmunotherapy (RIT) of EGFR-positive
      human head and neck cancer in a nude mouse model using pure beta(-) emitter (90)Y
      labeled panitumumab. Biodistribution and planar gamma-imaging studies were
      carried out with (111)In-DOTA-panitumumab. The RIT efficacy of (90)Y-DOTA
      panitumumab was evaluated in UM-SCC-22B tumor model. CD31, Ki67, terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labeling, and H&E staining
      were done on UM-SCC-22B tumor sections after treatment. The tumor uptake of
      (111)In-DOTA-panitumumab in UM-SCC-22B tumor-bearing nude mice was 26.10 +/-
      4.93, 59.11 +/- 7.22, 44.57 +/- 9.80, 40.38 +/- 7.76, and 14.86 +/- 7.23 %
      injected dose per gram of tissue at 4, 24, 72, 120, and 168 hours after
      injection, respectively. Immunotherapy with cold panitumumab (four doses of 10
      mg/kg) did not cause significant antitumor effect. RIT with a single dose of 100
      microCi (90)Y-DOTA-panitumumab caused significant tumor growth delay and improved
      the survival in UM-SCC-22B tumor model. A single dose of 200 microCi (90)Y-DOTA
      panitumumab led to almost complete tumor regression (tumor volumes were 34.83 +/-
      11.11 mm(3) and 56.02 +/- 39.95 mm(3) on days 0 and 46 after treatment,
      respectively). Histopathologic analysis of tumors and normal organs further
      validated the therapeutic efficacy and limited systemic toxicity of (90)Y-DOTA
      panitumumab. The high tumor uptake and prolonged tumor retention, as well as
      effective therapy, reveal that (90)Y-DOTA-panitumumab may be a promising
      radioimmunotherapeutic agent to treat EGFR-positive solid tumors.

PMID- 20682656
TI  - Galectin-3 promotes chronic activation of K-Ras and differentiation block in
      malignant thyroid carcinomas.
AB  - Anaplastic thyroid carcinomas are deadly tumors that are highly invasive,
      particularly into the bones. Although oncogenic Ras can transform thyroid cells
      into a severely malignant phenotype, thyroid carcinomas do not usually harbor ras
      gene mutations. Therefore, it is not known whether chronically active Ras
      contributes to thyroid carcinoma cell proliferation, although galectin-3 (Gal-3),
      which is strongly expressed in thyroid carcinomas but not in benign tumors or
      normal glands, is known to act as a K-Ras chaperone that stabilizes and drives K
      Ras.GTP nanoclustering and signal robustness. Here, we examined the possibility
      that thyroid carcinomas expressing high levels of Gal-3 exhibit chronically
      active K-Ras. Using cell lines representing three types of malignant thyroid
      tumors--papillary, follicular, and anaplastic--we investigated the possible
      correlation between Gal-3 expression and active Ras content, and then examined
      the therapeutic potential of the Ras inhibitor S-trans, trans
      farnesylthiosalicylic acid (FTS; Salirasib) for thyroid carcinoma. Thyroid
      carcinoma cells strongly expressing Gal-3 showed high levels of K-Ras.GTP
      expression, and K-Ras.GTP transmitted strong signals to extracellular signal
      regulated kinase. FTS disrupted interactions between Gal-3 and K.Ras, strongly
      reduced K-Ras.GTP and phospho-extracellular signal-regulated kinase expression,
      and enhanced the expression of the cell cycle inhibitor p21 as well as of the
      thyroid transcription factor 1, which is involved in thyroid cell
      differentiation. FTS also inhibited anaplastic thyroid carcinoma cell
      proliferation in vitro and tumor growth in nude mice. We conclude that wild-type
      K-Ras.GTP in association with Gal-3 contributes to thyroid carcinoma malignancy
      and that Ras inhibition might be a useful treatment strategy against these deadly
      tumors.

PMID- 20682655
TI  - Sorafenib activates CD95 and promotes autophagy and cell death via Src family
      kinases in gastrointestinal tumor cells.
AB  - Sorafenib and vorinostat interact in a synergistic fashion to kill carcinoma
      cells by activating CD95; the present studies have determined how sorafenib and
      vorinostat individually contribute to CD95 activation. Sorafenib (3-6 micromol/L)
      promoted a dose-dependent increase in Src Y416, ERBB1 Y845 and CD95 Y232/Y291
      phosphorylation, and Src Y527 dephosphorylation. Low levels of sorafenib-induced
      (3 micromol/L) CD95 tyrosine phosphorylation did not promote surface localization
      whereas sorafenib (6 micromol/L), or sorafenib (3 micromol/L) and vorinostat (500
      nmol/L) treatment promoted higher levels of CD95 phosphorylation which correlated
      with DISC formation, receptor surface localization, and autophagy. CD95 (Y232F,
      Y291F) was not tyrosine phosphorylated and was unable to localize plasma membrane
      or induce autophagy. Knockdown/knockout of Src family kinases abolished sorafenib
      induced CD95 tyrosine phosphorylation, DISC formation, and the induction of cell
      death and autophagy. Knockdown of platelet-ived growth factor receptor-beta
      enhanced Src Y416 and CD95 tyrosine phosphorylation, which correlated with
      elevated CD95 plasma membrane levels and autophagy, and with a reduced ability of
      sorafenib to promote CD95 membrane localization. Vorinostat increased reactive
      oxygen species levels, and in a delayed NF kappa B-dependent fashion, those of
      FAS ligand and CD95. Neutralization of FAS-L did not alter the initial rapid drug
      induced activation of CD95; however, neutralization of FAS-L reduced sorafenib +
      vorinostat toxicity by approximately 50%. Thus, sorafenib contributes to CD95
      activation by promoting receptor tyrosine phosphorylation, whereas vorinostat
      contributes to CD95 activation via the initial facilitation of reactive oxygen
      species generation and subsequently of FAS-L expression.

PMID- 20682657
TI  - Dual targeting of CDK and tropomyosin receptor kinase families by the oral
      inhibitor PHA-848125, an agent with broad-spectrum antitumor efficacy.
AB  - Altered expression and activity of cyclin-dependent kinase (CDK) and tropomyosin
      receptor kinase (TRK) families are observed in a wide variety of tumors. In those
      malignancies with aberrant CDK activation, the retinoblastoma protein (pRb)
      pathway is deregulated, leading to uncontrolled cell proliferation. Constitutive
      activation of TRKs is instead linked to cancer cell survival and dissemination.
      Here, we show that the novel small-molecule PHA-848125, a potent dual inhibitor
      of CDKs and TRKs, possesses significant antitumor activity. The compound inhibits
      cell proliferation of a wide panel of tumoral cell lines with submicromolar
      IC(50). PHA-848125-treated cells show cell cycle arrest in G(1) and reduced DNA
      synthesis, accompanied by inhibition of pRb phosphorylation and modulation of
      other CDK-dependent markers. The compound additionally inhibits phosphorylation
      of TRKA and its substrates in cells, which functionally express this receptor.
      Following oral administration, PHA-848125 has significant antitumor activity in
      various human xenografts and carcinogen-induced tumors as well as in disseminated
      primary leukemia models, with plasma concentrations in rodents in the same range
      as those found active in inhibiting cancer cell proliferation. Mechanism of
      action was also confirmed in vivo as assessed in tumor biopsies from treated
      mice. These results show that the dual CDK-TRK inhibitor PHA-848125 has the
      potential for being a novel and efficacious targeted drug for cancer treatment.

PMID- 20682658
TI  - Cisplatin treatment induces a transient increase in tumorigenic potential
      associated with high interleukin-6 expression in head and neck squamous cell
      carcinoma.
AB  - Head and neck squamous cell carcinoma (HNSCC) is characterized by the 5-year
      survival rate of approximately 50%. Despite aggressive surgical, radiation, and
      chemotherapeutic interventions, 30% to 40% of patients die from the development
      of recurrent or disseminated disease that is resistant to chemotherapy. As a
      model of recurrence, we examined the effects of cisplatin on the ability of head
      and neck cancer cells to initiate tumors in a xenotransplant model. HNSCC cells
      were treated in vitro with cisplatin at a concentration that elicited >99%
      cytotoxicity and assessed for tumorigenic potential in nonobese diabetic/severe
      combined immunodeficient mice. HNSCC cells that survived cisplatin treatment
      formed tumors in nonobese diabetic/severe combined immunodeficient mice more
      efficiently than nontreated cells. Cisplatin-resistant cells were characterized
      using clonal analysis, in vivo imaging, and transcriptomic profiling. Preliminary
      functional assessment of a gene, interleukin-6 (IL-6), highly upregulated in
      cisplatin-treated cells was carried out using clonogenicity and tumorigenicity
      assays. We show that cisplatin-induced IL-6 expression can contribute to the
      increase in tumorigenic potential of head and neck cancer cells but does not
      contribute to cisplatin resistance. Finally, through clonal analysis, we show
      that cisplatin-induced IL-6 expression and cisplatin-induced tumorigenicity are
      stochastically derived. We report that cisplatin treatment of head and neck
      cancer cells results in a transient accumulation of cisplatin-resistant, small,
      and IL-6-positive cells that are highly tumorigenic. These data also suggest that
      therapies that reduce IL-6 action may reduce recurrence rates and/or increase
      disease-free survival times in head and neck cancer patients, and thus, IL-6
      represents a promising new target in HNSCC treatment.

PMID- 20682659
TI  - Targeted inhibition of SRC kinase signaling attenuates pancreatic tumorigenesis.
AB  - Elevated Src expression correlates with malignant potential and metastatic
      disease in many tumors including pancreatic cancer. We sought to characterize the
      molecular effects of Src kinase inhibition with dasatinib (BMS-354825), a novel,
      multitargeted kinase inhibitor that targets Src family kinases in pancreatic
      ductal adenocarcinoma (PDA). We identified sensitive and resistant PDA cell lines
      to dasatinib treatment and tested the molecular effects of Src inhibition in
      vitro and in vivo. We show for the first time that cellular localization of Src
      expression affects survival in patients with PDA. Pancreatic tumors with
      increased membranous expression of Src resulted in decreased survival compared
      with tumors that had increased cytoplasmic Src expression. Src kinase inhibition
      with dasatinib markedly inhibits cell proliferation, migration, invasion, cell
      cycle progression and anchorage-independent growth, and stimulates apoptosis.
      This was accompanied by decreased phosphorylation of Src, focal adhesion kinase,
      paxillin, AKT, signal transducers and activators of transcription 3 (STAT3),
      extracellular signal-regulated kinase, and mitogen-activated protein kinase
      (MAPK), as well as decreased cyclin D1 expression in a time- and concentration
      dependent manner. Furthermore, small interfering RNA to Src results in a
      significant decrease in cell proliferation, invasion, and migration of pancreatic
      cancer cells. Dasatinib treatment also inhibits in vivo pancreatic tumor growth.
      Mechanisms of resistance to Src inhibition seem to be related to a lack of
      inhibition of STAT3 and MAPK signaling. These results establish a mechanistic
      rationale for Src inhibition with dasatinib as a therapeutic target in the
      treatment of pancreatic cancer and identify potential biomarkers of resistance to
      Src inhibition.

PMID- 20682660
TI  - Elevated serum interleukin 33 is associated with autoantibody production in
      patients with rheumatoid arthritis.
AB  - OBJECTIVE: Interleukin 33 (IL-33) is a novel cytokine involved in joint
      inflammation in animal models. We analyzed the expression of IL-33 in the serum
      and synovial fluid of patients with rheumatoid arthritis (RA) and investigated
      its possible pathophysiological importance. METHODS: The concentration of IL-33
      was measured by ELISA in the serum of 223 patients with RA and 159 controls.
      Anticyclic citrullinated peptide, rheumatoid factor (RF)-IgA, and RF-IgG were
      tested by ELISA. Antikeratin antibody and antiperinuclear factor were tested by
      indirect immunofluorescence assay. Erythrocyte sedimentation rate, C-reactive
      protein, and immunoglobulins were measured by standard laboratory techniques. The
      association of IL-33 level with clinical and serologic features of RA was
      analyzed. We tested the change of IL-33 level following tumor necrosis factor
      (TNF-alpha) blockade therapy in 40 patients with RA. RESULTS: In contrast to
      almost no detectable IL-33 in osteoarthritis and healthy serum, IL-33 could be
      detected in 94 out of the 223 RA cases (42.2%). Serum IL-33 concentration was
      significantly higher in patients with RA than in control groups. The level of
      serum IL-33 decreased after anti-TNF treatment. The level of serum IL-33 was
      correlated with the production of IgM and RA-related autoantibodies including RF
      and anticitrullinated protein antibodies. However, no correlation was found
      between IL-33 concentration and acute-phase inflammation reactant or the score of
      the Disease Activity Index, suggesting a complex or indirect character of the
      link between IL-33 and the inflammation in RA. CONCLUSION: The level of IL-33 is
      abnormally elevated in RA serum. The elevation of serum IL-33 was at least partly
      attributed to excessive TNF-alpha in RA. IL-33 might be involved in the
      regulation of autoantibody production in RA.

PMID- 20682661
TI  - Influence of CD40 rs1883832 polymorphism in susceptibility to and clinical
      manifestations of biopsy-proven giant cell arteritis.
AB  - OBJECTIVE: To assess the potential association between CD40 rs1883832
      polymorphism and biopsy-proven giant cell arteritis (GCA). We also studied the
      influence of the polymorphism on phenotypic expression of this vasculitis, in
      particular the development of visual ischemic manifestations. METHODS: Three
      hundred five Spanish patients with biopsy-proven GCA and 788 matched controls
      were assessed. DNA from patients and controls was obtained from peripheral blood.
      Samples were genotyped for the CD40 rs1883832 C/T polymorphism using a
      predesigned TaqMan allele discrimination assay and by polymerase chain reaction
      amplification. RESULTS: Patients with GCA showed a trend toward a higher
      frequency of the minor allele homozygote of rs1883832 (TT) compared to healthy
      controls (12.1% vs 8.3%, respectively; p = 0.05, OR 1.54, 95% CI 0.98-2.40).
      Also, a marginally significant increased frequency of the minor allele T was
      observed in patients with GCA who had visual ischemic manifestations (36.9%)
      compared to those without visual ischemic manifestations (27.7%; p = 0.04, OR
      1.53, 95% CI 0.99-2.34). In this regard, patients with GCA carrying the minor
      allele T (either TT or TC) experienced visual ischemic manifestations more
      commonly than those carrying the CC genotype (58.5% vs 44.2%; p = 0.04, OR 1.78,
      95% CI 0.99-3.22). CONCLUSION: Our results suggest a potential implication of the
      CD40 rs1883832 C/T polymorphism in susceptibility to visual ischemic
      manifestations in individuals with biopsy-proven GCA.

PMID- 20682662
TI  - Lack of association of C-C chemokine receptor 5 Delta32 deletion status with
      rheumatoid arthritis, systemic lupus erythematosus, lupus nephritis, and disease
      severity.
AB  - OBJECTIVE: C-C chemokine receptor 5 (CCR5) plays an important role in
      inflammation. A 32 base-pair (Delta32) deletion in the CCR5 gene leads to a
      nonfunctional receptor. This deletion has been reported to have a protective
      effect on the development and progression of several autoimmune diseases. We
      investigated whether the Delta32 deletion is associated with disease
      susceptibility in a population of patients with rheumatoid arthritis (RA),
      systemic lupus erythematosus (SLE), and lupus nephritis (LN); and whether it is
      associated with disease severity. METHODS: DNA samples from 405 RA patients, 97
      SLE patients, 113 LN patients, and 431 healthy controls were genotyped for the
      CCR5 Delta32 deletion. Differences in genotype frequencies were tested between
      patients and controls. Association of genotypes with disease severity was
      analyzed. RESULTS: Genotype frequencies of each group were in Hardy-Weinberg
      equilibrium. The genotype frequencies of patients did not differ significantly
      from controls (CCR5/Delta32, Delta32/Delta32: RA 18.3% and 1.2%, respectively;
      SLE 17.5% and 2.1%; LN 13.3% and 1.8%; controls 20.0% and 2.8%). However, there
      was a trend for lower Delta32 deletion allele frequency in LN patients compared
      to controls (p = 0.08). There was no significant association between the CCR5
      status and disease severity in RA, SLE, or LN. CONCLUSION: Although an
      association with LN cannot be excluded, the CCR5 Delta32 deletion does not seem
      to be a disease susceptibility genotype for RA, SLE, or LN. No significant effect
      of the Delta32 deletion on disease severity was demonstrated.

PMID- 20682663
TI  - Anti-Th/To are common antinucleolar autoantibodies in Italian patients with
      scleroderma.
AB  - OBJECTIVE: Patients with scleroderma (systemic sclerosis; SSc) can be classified
      into subsets based on autoantibody profile and clinical features. Specificities
      such as anti-Th/To and anti-fibrillarin (U3RNP) are detectable mainly by
      immunoprecipitation (IP), which is not widely used in clinical laboratories. We
      examined the autoantibody profiles and clinical manifestations in a cohort of
      Italian patients with SSc, focusing on anti-Th/To and anticentromere (ACA)
      antibodies, associated with limited cutaneous SSc (lcSSc). METHODS: Sera from 216
      consecutive patients with SSc were tested for ACA (by indirect
      immunofluorescence), antitopoisomerase I (topo I; by
      counterimmunoelectrophoresis), and anti-RNA polymerase III (RNAPIII; by ELISA).
      Forty-one sera negative for these specificities were tested by IP analysis of
      proteins ((35)S-methionine labeled K562 cell extract) and RNA (silver staining).
      RESULTS: Among 216 SSc patients analyzed, anti-topo I, ACA, and anti-RNAPIII were
      detected in 38% (81/216), 31% (67/216) and 7% (15/216), respectively. Among 41
      sera negative for ACA, anti-topo I, and anti-RNAPIII and which were tested by IP,
      14 were nucleolar stain-positive. Eight out of 14 (57%) showed anti-Th/To
      reactivity, but no anti-U3RNP was found. In comparison with ACA-positive
      patients, anti-Th/To-positive patients were younger (p = 0.0046) and more
      commonly were male (p = 0.0006). All 8 anti-Th/To-positive and all but one ACA
      positive patients had lcSSc. Interstitial lung disease (ILD) and pericarditis
      were more frequent in anti-Th/To-positive patients. CONCLUSION: Anti-Th/To are
      common in antinucleolar antibody-positive Italian patients with SSc. Anti-Th/To
      and ACA patients had lcSSc, with excellent prognosis. The anti-Th/To group had
      frequent pericarditis and ILD, although impairment of pulmonary function appeared
      mild.

PMID- 20682664
TI  - Increased interleukin 21 (IL-21) and IL-23 are associated with increased disease
      activity and with radiographic status in patients with early rheumatoid
      arthritis.
AB  - OBJECTIVE: To investigate the levels of the T helper (Th)17-related cytokines
      interleukin 17A (IL-17A), IL-21, and IL-23 and their association with disease
      activity in rheumatoid arthritis (RA). METHODS: In a longitudinal sample set from
      patients with early RA (< 6 months; n = 40), we measured the plasma cytokine
      levels of IL-17A, IL-21, and IL-23 and analyzed for correlation with disease
      activity in 28 joints (Disease Activity Score 28-joint count; DAS28), C-reactive
      protein (CRP), erythrocyte sedimentation rate (ESR), and total Sharp score (TSS).
      In a transverse sample set of patients with chronic RA (> 8 years), using paired
      peripheral blood mononuclear cells and synovial fluid mononuclear cells, we
      investigated the cellular expression of IL-17A, IL-21, and IL-23R. RESULTS:
      Patients with early-stage RA had significantly increased plasma levels of IL-21
      and IL-23, but not IL-17A, compared to patients with chronic RA and healthy
      volunteer controls. Plasma levels of IL-21 and IL-23 after 12 months of treatment
      correlated with DAS28 and ESR, but not to TSS. Changes in IL-23 plasma levels
      from time of diagnosis to 12 months correlated with change in DAS28 and with TSS
      scores at 2 years. The numbers of CD4+ T cells producing IL-21 were significantly
      increased in the synovial fluid of patients with chronic RA, with only marginal
      coexpression of IL-21 and IL-17A. CONCLUSION: Our results show a significant
      association between plasma levels of IL-21 and IL-23 and disease activity in RA,
      supporting the hypothesis that IL-21 and IL-23 are important pathogenic factors
      of this disease.

PMID- 20682665
TI  - Impaired health-related quality of life in patients treated for Wegener's
      granulomatosis.
AB  - OBJECTIVE: To investigate whether patients with Wegener's granulomatosis (WG)
      experience reduced health-related quality of life (HRQOL) after accomplishment of
      remission, and to study the influence of WG-associated organ damage on HRQOL.
      METHODS: Sixty-eight patients with inactive WG and 680 randomly selected, age-
      and sex-matched controls of the Danish background population completed the
      Medical Outcomes Study Short-Form 36 (SF-36) survey for evaluation of HRQOL.
      Irreversible organ damage attributable to WG and/or its treatment was assessed
      using the Vasculitis Damage Index (VDI). RESULTS: The median disease duration was
      7.5 (range 1-26) years in the WG group, and the median total VDI score was 2.0
      (range 0-7). Compared to controls, WG patients reported impaired HRQOL reflected
      by significantly lower SF-36 physical component summary scores (PCS) and mental
      component summary scores (MCS) (p < 0.001) and by significantly lower scores in 7
      out of 8 SF-36 subscales (p <= 0.001). In the WG group, no statistically
      significant correlations were found between the different SF-36 scores and the
      total VDI score, number of organ systems affected by damage, disease duration, or
      number of WG relapses. Patients with organ failure or other major forms of damage
      did not report significantly lower HRQOL than less severely affected patients.
      CONCLUSION: WG patients experience significantly reduced HRQOL even in phases
      with no apparent vasculitis disease activity. Our data indicate that the level of
      HRQOL does not correlate well with the extent of vasculitis-associated organ
      damage in WG.

PMID- 20682666
TI  - Musculoskeletal complications of hereditary hemochromatosis: a case-control
      study.
AB  - OBJECTIVE: Arthropathy that mimics osteoarthritis (OA) and osteoporosis (OP) is
      considered a classic complication of hereditary hemochromatosis (HH) but has
      never been investigated in a cross-sectional study. We investigated whether HH is
      associated with increased prevalence of OA and OP and related factors. METHODS: A
      self-administered questionnaire was completed by 306 patients with HH and 304 age
      and sex-matched unaffected controls. RESULTS: The mean age of patients was 60.1
      +/- 11.3 years, and 47.4% were women. More patients with HH than controls had
      been given a diagnosis of OA: 50.5% vs 28.9% [adjusted OR (aOR) 2.5, 95% CI 1.8
      3.6]. Compared with controls, patients with HH had a higher risk of knee (aOR
      5.3, 95% CI 1.1-25.6) and hip replacement prosthesis (aOR 5.2, 95% CI 2.2-11.9).
      More patients than controls had been diagnosed with OP: 23.3% vs 4.6% (aOR 7.3,
      95% CI 3.2-17.0). Patients with HH showed an increased prevalence, although not
      significant, of wrist (aOR 1.7, 95% CI 0.9-3.0) or vertebral fractures (aOR 1.7,
      95% CI 0.8-3.8). The severity of iron overload, as defined by a ferritin level >
      1000 MUg/l at diagnosis, was associated with OA (p = 0.0005), OP (p = 0.01),
      presence of hip prosthesis (p = 0.04), wrist fractures (p = 0.002), and vertebral
      fractures (p = 0.02). CONCLUSION: This case-control study strongly suggests a
      significant association among HH, OA, and OP. Joint involvement can be severe,
      especially in patients with substantially elevated ferritin levels.

PMID- 20682667
TI  - Evaluation of ankylosing spondylitis quality of life (EASi-QoL): reliability and
      validity of a new patient-reported outcome measure.
AB  - OBJECTIVE: There is currently no universally accepted measure of quality of life
      in ankylosing spondylitis (AS). Our objective was to develop and evaluate a
      patient-reported outcome measure of quality of life in AS, EASi-QoL. METHODS: We
      used patient interviews, a literature review, and completion of an individualized
      measure of AS quality of life during clinic-based and pilot surveys to derive
      questionnaire content. Classical and modern psychometrics were then used to
      evaluate the questionnaire using data from a large UK-based postal survey of 1000
      patients with AS. RESULTS: Data analysis from the interviews and clinic-based and
      postal surveys produced a 57-item self-completed questionnaire. Fifteen items
      were removed as a result of patient interviews and the pilot survey. In total,
      612 (64.0%) patients responded to the main postal survey. After assessment of
      data quality, confirmatory factor analysis, and Rasch analysis, 20 items were
      found to contribute to 4 domains of AS-related quality of life: physical
      function, disease activity, emotional well-being, and social participation. Item
      total correlations ranged from 0.66 to 0.84. Cronbach's alpha and test-retest
      reliability estimates were 0.88-0.92 and 0.88-0.93, respectively. Confirmed
      hypothesized correlations with the AS Quality of Life questionnaire, the Bath AS
      Disease Activity Index, Bath AS Functional Index, SF-36, EQ-5D, and the Hospital
      Anxiety and Depression Scale were evidence for the construct validity of the EASi
      QoL. CONCLUSION: The EASi-QoL has good evidence of data quality, internal
      reliability, test-retest reliability, and content and construct validity, and
      should be considered for use with patients in routine practice settings and in
      evaluative studies including clinical trials. Measurement responsiveness and
      minimal important change are currently being assessed.

PMID- 20682668
TI  - Spondyloarthritis in a pediatric population: risk factors for sacroiliitis.
AB  - OBJECTIVE: Pediatric rheumatologists may have an opportunity to diagnose
      sacroiliitis in its early stages, prior to the development of irreversible
      radiographic changes. Early diagnosis frequently requires magnetic resonance
      imaging (MRI), the use of which is limited by expense and requirement for
      sedation. We set out to identify features of juvenile spondyloarthritis (SpA)
      associated with the highest risk of sacroiliitis, to identify patients who may be
      candidates for routine MRI-based screening. METHODS: We reviewed the charts of
      143 children seen at Texas Scottish Rite Hospital for Children diagnosed with SpA
      based on the International League of Associations for Rheumatology criteria for
      enthesitis-related arthritis or the Amor criteria for SpA. We performed logistic
      regression analysis to identify risk factors for sacroiliitis. RESULTS: A group
      of 143 children were diagnosed with SpA. Consistent with the diagnosis of SpA,
      16% had psoriasis, 43% had enthesitis, 9.8% had acute anterior uveitis, and 70%
      were HLA-B27+. Fifty-three children had sacroiliitis, of which 11 cases were
      identified by imaging studies in the absence of suggestive symptoms or physical
      examination findings. Logistic regression analysis revealed that hip arthritis
      was a positive predictor of sacroiliitis, while dactylitis was a negative
      predictor. CONCLUSION: Children with SpA are at risk for sacroiliitis, which may
      be present in the absence of suggestive symptoms or physical examination
      findings. The major risk factor for sacroiliitis is hip arthritis, while
      dactylitis may be protective. Routine screening by MRI should be considered in
      patients at high risk of developing sacroiliitis.

PMID- 20682669
TI  - Effects of sodium oxybate on sleep physiology and sleep/wake-related symptoms in
      patients with fibromyalgia syndrome: a double-blind, randomized, placebo
      controlled study.
AB  - OBJECTIVE: To determine the effects of sodium oxybate (SXB) on sleep physiology
      and sleep/wake-related symptoms in patients with fibromyalgia syndrome (FM).
      METHODS: Of 304 patients with FM (American College of Rheumatology tender point
      criteria) in the screened study population, 209 underwent polysomnography, 195
      were randomized, and 151 completed this 8-week, double-blind, placebo-controlled
      study of SXB 4.5 g and 6 g/night. We evaluated changes in objective sleep
      measures and subjective symptoms, including daytime sleepiness [Epworth
      Sleepiness Scale (ESS)], fatigue visual analog scale (FVAS), sleep [Jenkins Scale
      for Sleep (JSS)], and daytime functioning [Functional Outcome of Sleep
      Questionnaire (FOSQ), SF-36 Vitality domain, and Fibromyalgia Impact
      Questionnaire (FIQ) general and morning tiredness]. RESULTS: Pretreatment
      screening revealed an elevated incidence of maximum alpha EEG-intrusion > 24
      min/hour of sleep (66%), periodic limb movements of sleep (20.1% >= 5/hour), and
      moderate to severe obstructive sleep apnea disorder (15.3% apnea-hypopnea index
      >= 15/hour). Compared with placebo, both doses of SXB achieved statistically
      significant improvements in ESS, morning FVAS, JSS, FOSQ, SF-36 Vitality, and FIQ
      general and morning tiredness; both doses also demonstrated decreased rapid eye
      movement (REM) sleep (all p <= 0.040). SXB 6 g/night improved afternoon, evening
      and overall FVAS, reduced wakefulness after sleep onset, and increased Stage 2,
      slow-wave, and total non-REM sleep (all p <= 0.032) versus placebo. Moderate
      correlations (>= 0.40) were noted between changes in subjective sleep and pain
      measures. Adverse events occurring significantly more frequently with SXB than
      placebo were nausea, pain in extremity, nervous system disorders, dizziness,
      restlessness, and renal/urinary disorders (including urinary incontinence).
      CONCLUSION: This large cohort of patients with FM demonstrated that SXB treatment
      improved EEG sleep physiology and sleep-related FM symptoms.

PMID- 20682670
TI  - Mortality in psoriatic arthritis - a single-center study from the UK.
AB  - OBJECTIVE: To determine whether the mortality in a cohort of patients with
      psoriatic arthritis (PsA) from a single center in the UK is significantly
      different from the general UK population. METHODS: Patients who were entered onto
      the PsA database at the Royal National Hospital for Rheumatic Diseases, Bath,
      between 1985 and 2007 were included in this study. Information on patient deaths
      was collected retrospectively. The National Health Service (NHS) Strategic
      Tracing Service was used to establish which patients were alive and which had
      died. Date and cause of death were confirmed by death certificates from the
      Registry of Births, Marriages and Deaths. A standardized mortality ratio (SMR)
      was calculated by matching the patient data to single-year, 5-year age-banded
      England and Wales data from the Office of National Statistics. RESULTS: In this
      cohort of 453 patients with PsA (232 men, 221 women), there were 37 deaths.
      Sixteen men and 21 women died. The SMR for the men was 67.87% (95% CI 38.79,
      110.22), and for the women, 97.01% (95% CI 60.05, 148.92) and the overall SMR for
      the PsA cohort was 81.82% (95% CI 57.61, 112.78). The leading causes of death in
      this cohort were cardiovascular disease (38%), diseases of the respiratory system
      (27%), and malignancy (14%). CONCLUSION: These results suggest that mortality in
      our single-center PsA cohort is not significantly different from the general UK
      population. No increased risk of death was observed in this cohort.

PMID- 20682671
TI  - Hypothalamus-pituitary-adrenal axis function in patients with rheumatoid
      arthritis treated with nighttime-release prednisone.
AB  - OBJECTIVE: To investigate the effects of longterm low-dose chronotherapy with
      modified-release (MR) prednisone for rheumatoid arthritis (RA) on the
      hypothalamus-pituitary-adrenal (HPA) axis as part of the Circadian Administration
      of Prednisone in Rheumatoid Arthritis (CAPRA-1) study. This consisted of a 3
      month active-controlled phase and a 9-month open-label extension with MR
      prednisone including patients previously treated with prednisone
      (ClinicalTrials.gov number NCT00146640). METHODS: Corticotropin-releasing hormone
      (CRH) tests were performed on 28 patients at 3 timepoints: at baseline on
      prestudy immediate-release (IR) prednisone, after the 3-month double-blind phase
      on either IR prednisone or MR prednisone, and after the 9-month open-label
      extension on MR prednisone. Changes of cortisol were assessed and compared to
      individual patients' efficacy and safety data. RESULTS: The increase (mean, SD)
      of cortisol plasma concentrations after injection of corticorelin was 5.5 (4.37)
      MUg/dl on IR prednisone at baseline (n = 21) and 5.3 (4.07) MUg/dl on MR
      prednisone at 12 months (n = 22). Numbers of normal/suppressed/no response
      reactions did not differ among treatments. Switching from IR to MR prednisone did
      not influence responses, nor did longterm treatment of up to 12 months with MR
      prednisone. No worsening of adrenal impairment was observed on treatment with
      nighttime-release prednisone in patients with low responsiveness to CRH testing
      before the treatment with MR prednisone. CONCLUSION: Treatment with nighttime
      release prednisone did not change adrenocortical function over 12 months. We
      presume that chronotherapy with this nighttime-release prednisone may improve the
      efficacy of longterm low-dose glucocorticoid treatment in patients with RA.

PMID- 20682672
TI  - The relation of interleukin 17 (IL-17) and IL-23 to Th1/Th2 cytokines and disease
      activity in systemic lupus erythematosus.
AB  - OBJECTIVE: Interleukin 17 (IL-17) was recently linked to pathogenesis of systemic
      lupus erythematosus (SLE), but its relation to disease activity has not been well
      characterized. We examined the relation between serum levels of Th17 (IL-17, IL
      23), Th1 (IL-12, interferon-gamma), Th2 (IL-10, IL-6, IL-4) cytokines and disease
      activity in patients with SLE. METHODS: Serum cytokines were measured by enzyme
      linked immunosorbent assays. Disease activity was determined by SLE disease
      activity index (SLEDAI), anti-dsDNA antibody, and C3 and C4 levels. RESULTS:
      Serum levels of IL-17 (p < 0.001), IL-6 (p = 0.006) and IL-10 (p < 0.001) were
      higher in SLE patients (n = 70) compared to healthy controls (n = 36). Higher
      serum IL-23 level was found in patients with active disease with cutaneous
      manifestations (p = 0.004) and serositis (p = 0.04) compared to those without.
      Serum IL-17 level above the detection limit was more frequently found in patients
      who had active lupus nephritis (11/23, 47.8%) (p = 0.002), nonrenal active
      disease (9/15, 60%) (p = 0.001), and inactive lupus (21/32, 65.6%) (p < 0.001)
      compared to healthy controls (0%). Serum IL-17 levels were otherwise comparable
      between these 3 groups of patients and were not related to SLEDAI, glomerular
      filtration rate, activity or chronicity score and ISN/RPS criteria class among
      patients with active lupus nephritis. There was no significant correlation
      between serum IL-17/IL-23 and Th1 or Th2 cytokine levels. CONCLUSION: SLE
      patients had higher serum IL-17 levels than healthy controls. Elevated serum IL
      23 was found in patients with inflammatory manifestations including cutaneous
      involvement and serositis. The lack of correlation between Th17, Th1, and Th2
      cytokines suggested independent regulatory mechanisms for these cytokines.

PMID- 20682673
TI  - Nuclear magnetic resonance lipoprotein subclasses and the APOE genotype influence
      carotid atherosclerosis in patients with systemic lupus erythematosus.
AB  - OBJECTIVE: Patients with systemic lupus erythematosus (SLE) have accelerated
      atherosclerosis. Since the conventional lipid profile (total plasma cholesterol,
      triglycerides, low and high density lipoprotein cholesterol) is not consistently
      altered in SLE, we hypothesized that investigation of lipoprotein subclasses
      would improve prediction of risk of atherosclerosis in these patients. METHODS:
      As a quantitative index of atherosclerosis, we measured the carotid intima-media
      thickness (IMT) in 68 patients with SLE and related the atherosclerosis to a
      detailed lipoprotein profile generated using nuclear magnetic resonance (NMR). We
      measured the cholesterol transported by the pool of remnant lipoproteins (RLPc)
      and evaluated the modulatory effect of the APOE genotype on the lipoprotein
      subclass profile and atherosclerosis associated with SLE. RESULTS: Circulating
      lipoprotein remnant particles [RLPc and intermediate density lipoprotein (IDL)]
      were positively correlated with IMT, and among them, the indicator that explained
      20.2% of the variability in carotid atherosclerosis measured in these patients
      was IDL, as assessed by NMR. Carriers of the APOE2 allele were at increased risk
      due to a significant accumulation of IDL particles. CONCLUSION: Lipoprotein
      subclasses are more associated with subclinical atherosclerosis in patients with
      SLE than the lipid variables that are routinely measured. The IDL fraction, which
      is significantly modulated by the APOE genotype, is the most strongly,
      significantly, and positively correlated with IMT.

PMID- 20682674
TI  - Effect of psychological distress on continuation of anti-tumor necrosis factor
      therapy in patients with rheumatoid arthritis.
AB  - OBJECTIVE: To investigate the relationship of psychological distress and
      associated factors with continuation of tumor necrosis factor (TNF) antagonist
      therapy in patients with rheumatoid arthritis (RA). METHODS: Patients about to
      start therapy with TNF antagonists (n = 166) were assessed for psychological
      distress using the Hospital Anxiety and Depression Scale (HADS). A core set of
      demographic and clinical variables, including comorbidities from medical records
      and cigarette smoking history by questionnaire, were recorded at baseline and
      regular intervals thereafter. Cox proportional hazards regression analysis was
      used to assess the likelihood of patients discontinuing therapy over a 36-month
      followup period. RESULTS: The number of years smoked was associated with anxiety
      (HADS-A; p for trend = 0.008) and general psychological distress (HADS-Total; p
      for trend = 0.03). In univariate analyses, earlier discontinuation was associated
      with these variables at baseline: anxiety (HADS-A), depression (HADS-D), abnormal
      mood (HADS-Total), smoking history (> 30 pack-yrs), years smoked (> 30 yrs),
      current smoking, high Disease Activity Score 28-joint count (DAS28), poor patient
      global assessment, and evidence of cardio/cerebrovascular disease (CVD). In
      multivariate analyses, the strongest predictors of discontinuation were HADS
      Total, smoking history (> 30 pack-yrs), DAS28, and evidence of CVD at baseline.
      CONCLUSION: Discontinuation of therapy with TNF antagonists is independently
      associated with psychological distress, heavy smoking, and CVD at baseline.

PMID- 20682675
TI  - Levels of transforming growth factor-beta are low in systemic lupus erythematosus
      patients with active disease.
AB  - OBJECTIVE: Cytokines are central regulators of the immune response but the
      workings of this complex network in systemic lupus erythematosus (SLE) are not
      fully understood. We investigated a range of inflammatory and immune-modulating
      cytokines to determine their value as biomarkers for disease subsets in SLE.
      METHODS: This was a cross-sectional study in 102 patients with SLE (87% women,
      disease duration 10.6 yrs). Circulating concentrations of interleukin 1beta (IL
      1beta), IL-4, IL-6, IL-10, IL-12, IL-17, monocyte chemotactic protein 1 (MCP-1),
      macrophage inflammatory protein 1 (MIP-1alpha), MIP-1beta, interferon-gamma (IFN
      gamma), tumor necrosis factor-alpha (TNF-alpha), and total transforming growth
      factor-beta1 (TGF-beta1) were related to disease activity (SLE Disease Activity
      Index; SLEDAI), lymphocyte subsets, autoantibody levels, accrued damage (Systemic
      Lupus International Collaborating Clinics/ACR Damage Index; SDI), and concomitant
      treatment. RESULTS: Patients with SLE had lower levels of TGF-beta1 (p = 0.01)
      and IL-1beta (p = 0.0004) compared to controls. TGF-beta1 levels were lower in
      patients with SLEDAI scores 1-10 and SDI > 3; and were correlated with CD4+,
      CD8+, and natural killer cell counts; and were independent of steroid or
      cytotoxic drug use. Treatment with cardiovascular drugs was associated with lower
      IL-12 levels. No consistent disease associations existed for the other cytokines
      investigated. CONCLUSION: Lower TGF-beta1 was the most consistent cytokine
      abnormality in patients with SLE. The associations with disease activity,
      lymphocyte subsets, and damage suggest that TGF-beta1 may be a therapeutic target
      of interest in SLE.

PMID- 20682676
TI  - Efficacy of cognitive-behavioral therapies in fibromyalgia syndrome - a
      systematic review and metaanalysis of randomized controlled trials.
AB  - OBJECTIVE: We performed the first systematic review with metaanalysis of the
      efficacy of cognitive-behavioral therapies (CBT) in fibromyalgia syndrome (FM).
      METHODS: We screened Cochrane Library, Medline, PsychINFO, and Scopus (through
      June 2009) and the reference sections of original studies and systematic reviews
      for CBT in FM. Randomized controlled trials (RCT) comparing CBT to controls were
      analyzed. Primary outcomes were pain, sleep, fatigue, and health-related quality
      of life (HRQOL). Secondary outcomes were depressed mood, self-efficacy pain, and
      healthcare-seeking behavior. Effects were summarized using standardized mean
      differences (SMD). RESULTS: A total of 14 out of 27 RCT with 910 subjects with a
      median treatment time of 27 hours (range 6-75) over a median of 9 weeks (range 5
      15) were included. CBT reduced depressed mood (SMD -0.24, 95% CI -0.40, -0.08; p
      = 0.004) at posttreatment. Sensitivity analyses showed that the positive effect
      on depressed mood could not be distinguished from some risks of bias. There was
      no significant effect on pain, fatigue, sleep, and HRQOL at posttreatment and at
      followup. There was a significant effect on self-efficacy pain posttreatment (SMD
      0.85, 95% CI 0.25, 1.46; p = 0.006) and at followup (SMD 0.90, 95% CI 0.14, 1.66;
      p = 0.02). Operant behavioral therapy significantly reduced the number of
      physician visits at followup (SMD -1.57, 95% CI -2.00, -1.14; p < 0.001).
      CONCLUSION: CBT can be considered to improve coping with pain and to reduce
      depressed mood and healthcare-seeking behavior in FM.

PMID- 20682677
TI  - Association of bone morphogenetic proteins with spinal fusion in ankylosing
      spondylitis.
AB  - OBJECTIVE: To measure serum concentrations of bone morphogenetic proteins (BMP)
      in patients with ankylosing spondylitis (AS), and to investigate the relationship
      between BMP and clinical manifestations and radiographic changes. METHODS: We
      studied 60 consecutive AS patients with and 60 patients without spinal fusion.
      Spinal radiographs were assessed using the Bath Ankylosing Spondylitis Radiology
      Index (BASRI) and the modified Stoke Ankylosing Spondylitis Spinal Score
      (mSASSS). Spinal fusion was defined as the presence of total bony bridging
      between 2 adjacent vertebral bodies in either the lumbar or cervical spine. Serum
      levels of BMP were determined by enzyme-linked immunosorbent assay. RESULTS:
      Patients with spinal fusion had higher serum levels of BMP-2 and BMP-4 than
      either the healthy controls or patients without spinal fusion (p < 0.001), but
      there was no difference between the latter 2 groups. Serum BMP-7, erythrocyte
      sedimentation rate, and C-reactive protein (CRP) levels were elevated in patients
      with spinal fusion compared with those without (p < 0.05). Serum BMP-4 and BMP-7
      levels were higher in patients with hip involvement than in those without (p <
      0.05). BMP-2 and BMP-4 levels had a significant correlation with spinal
      radiograph scores, especially for BASRI of the lumbar spine (r = 0.356 and 0.348,
      respectively, p < 0.001). CRP showed a significant correlation with spine BASRI
      and mSASSS scores (r = 0.261 and 0.260, respectively, p < 0.05). CONCLUSION:
      Rising levels of BMP in AS patients with spinal fusion and the positive
      correlation between BMP and spinal radiograph scores indicate that BMP may play a
      role in the process of spinal ankylosis. Serum levels of BMP may reflect
      radiographic progression of the spine and hip joints.

PMID- 20682678
TI  - Low plasma adiponectin as a potential biomarker for osteonecrosis of the femoral
      head.
AB  - OBJECTIVE: To examine whether plasma adiponectin level is correlated with
      osteonecrosis of the femoral head (ONFH). METHODS: Blood adiponectin level in
      patients with nontraumatic ONFH (n = 120) was compared with a group of healthy
      subjects (n = 120). Patients with hip osteoarthritis (OA; n = 30) and traumatic
      ONFH (n = 45) were included as controls. Potential compounding factors, such as
      plasma low-density lipoprotein (LDL), high-density lipoprotein (HDL),
      apolipoprotein A1 (apo A1), apolipoprotein B (apo B), total cholesterol (TC),
      triglycerides (TG), and C-reactive protein (CRP) were also examined. RESULTS:
      Patients with nontraumatic ONFH had significantly lower plasma levels of
      adiponectin than the healthy controls (7.14 +/- 3.53 vs 10.93 +/- 3.41 MUg/ml,
      respectively; p < 0.001). Adiponectin level was positively correlated with HDL (r
      = 0.282, p < 0.001) and age (r = 0.145, p = 0.01), yet negatively correlated with
      body mass index (r = -0.70, p < 0.001), TG (r = -0.55, p<0.001), LDL/HDL ratio (r
      = -0.173, p = 0.002), and CRP (r = -0.634, p < 0.001). No correlation was seen
      with LDL (r = -0.017, p = 0.762). A multiple logistic regression analysis
      revealed that adiponectin level is an independent predictor of the presence of
      nontraumatic ONFH (p < 0.001, OR 0.676, 95% CI 0.546 to 0.845). CONCLUSION: Low
      adiponectin level is significantly associated with the presence of nontraumatic
      ONFH. This biomarker may be useful in assessing the potential presence of
      nontraumatic ONFH.

PMID- 20682679
TI  - A 1-year lifestyle intervention for weight loss in individuals with type 2
      diabetes reduces high C-reactive protein levels and identifies metabolic
      predictors of change: from the Look AHEAD (Action for Health in Diabetes) study.
AB  - OBJECTIVE: We examined whether a 1-year intensive lifestyle intervention (ILI)
      for weight loss reduced elevated high-sensitivity C-reactive protein (hs-CRP)
      levels in obese individuals with diabetes and identified metabolic and fitness
      predictors of hs-CRP change. RESEARCH DESIGN AND METHODS: Look AHEAD (Action for
      Health in Diabetes) is an ongoing multicenter clinical trial examining the
      effects of weight loss achieved through ILI on cardiovascular events and overall
      mortality in obese/overweight adults with type 2 diabetes. We report on 1,759
      Look AHEAD participants who had hs-CRP and fitness data at baseline and 1 year.
      Subjects were randomly assigned to ILI or to usual care (diabetes support and
      education [DSE]). ILI involved frequent counseling to increase moderate-intensity
      exercise to 175 min/week, reduce caloric and saturated fat intake, and change
      macronutrient composition to improve glycemic control. RESULTS: ILI reduced
      median hs-CRP by 43.6% from baseline to 1 year, compared with a 16.7% reduction
      with DSE (P<0.001). ILI decreased weight (8.8%), A1C (0.7%), and triglycerides
      (17%) and increased fitness (19%) and HDL cholesterol (7.5%) (P<0.0001 vs.
      changes with DSE). Changes in adiposity and glucose control with ILI remained
      independent predictors of hs-CRP change at 1 year (P<0.0001 for each) after
      adjustment for demographics, smoking, cardiovascular history, statin and
      thiazolidinedione use, and changes in fitness and lipid control. Neither statin
      nor insulin therapy modified the association between ILI and hs-CRP. CONCLUSIONS:
      A 1-year lifestyle intervention for weight loss in obese individuals with
      diabetes was associated with substantial reductions in hs-CRP. Improved glycemic
      control and reduced adiposity had comparable effects on hs-CRP change.

PMID- 20682680
TI  - Acute pancreatitis in type 2 diabetes treated with exenatide or sitagliptin: a
      retrospective observational pharmacy claims analysis.
AB  - OBJECTIVE: Cases of acute pancreatitis have been reported in association with
      exenatide, sitagliptin, and type 2 diabetes without use of these medications. It
      remains unknown whether exenatide or sitagliptin increase the risk of acute
      pancreatitis. RESEARCH DESIGN AND METHODS: A retrospective cohort study of a
      large medical and pharmacy claims database was performed. Data for 786,656
      patients were analyzed. Cox proportional hazard models were built to compare the
      risk of acute pancreatitis between diabetic and nondiabetic subjects and between
      exenatide, sitagliptin, and control diabetes medication use. RESULTS: Incidence
      of acute pancreatitis in the nondiabetic control group, diabetic control group,
      exenatide group, and sitagliptin group was 1.9, 5.6, 5.7, and 5.6 cases per 1,000
      patient years, respectively. The risk of acute pancreatitis was significantly
      higher in the combined diabetic groups than in the nondiabetic control group
      (adjusted hazard ratio 2.1 [95% CI 1.7-2.5]). Risk of acute pancreatitis was
      similar in the exenatide versus diabetic control group (0.9 [0.6-1.5]) and
      sitagliptin versus diabetic control group (1.0 [0.7-1.3]). CONCLUSIONS: Our study
      demonstrated increased incidence of acute pancreatitis in diabetic versus
      nondiabetic patients but did not find an association between the use of exenatide
      or sitagliptin and acute pancreatitis. The limitations of this observational
      claims-based analysis cannot exclude the possibility of an increased risk.

PMID- 20682681
TI  - Importance of time spent standing for those at risk of diabetic foot ulceration.
AB  - OBJECTIVE: Despite the high cumulative plantar stress associated with standing,
      previous physical activity reports of diabetic patients at risk of foot
      ulceration have not taken this activity into account. This study aimed to monitor
      spontaneous daily physical activity in diabetic peripheral neuropathy (DPN)
      patients and examine both walking and standing activities as important foot
      loading conditions. RESEARCH DESIGN AND METHODS: Thirteen DPN patients were asked
      to wear a body-worn sensor for 48 h. Body postures (sitting, standing, and lying)
      and locomotion (walking, number of steps, and postural transition) were
      extracted. RESULTS: Patients daily spent twice as much time standing (13+/-5%) as
      walking (6+/-3%). They spent 37+/-6% of time sitting and 44+/-8% lying down. The
      average number of steps per day was 7,754+/-4,087, and the number of walking
      episodes was 357+/-167 with maximum duration of 3.9+/-3.8 min. CONCLUSIONS: The
      large portion of DPN patients' time spent standing with the feet loaded requires
      further consideration when treating and preventing foot ulcers.

PMID- 20682683
TI  - Glucose excursions between states of glycemia with progression to type 1 diabetes
      in the diabetes prevention trial-type 1 (DPT-1).
AB  - OBJECTIVE: We characterized fluctuations between states of glycemia in
      progressors to type 1 diabetes and studied whether those fluctuations are related
      to the early C-peptide response to oral glucose. RESEARCH DESIGN AND METHODS:
      Oral glucose tolerance tests (OGTTs) from differing states of glycemia were
      compared within individuals for glucose and C-peptide. Dysglycemic OGTTs
      (DYSOGTTs) were compared with normal OGTTs (NLOGTT), while transient diabetic
      OGTTs (TDOGTTs) were compared with subsequent nondiabetic OGTTs and with OGTTs
      performed at diagnosis. RESULTS: Of 135 progressors with four or more OGTTs, 30
      (22%) went from NLOGTTs to DYSOGTTs at least twice. Area under the curve (AUC)
      glucose values from the second NLOGTT were higher (P < 0.001) than values from
      the first NLOGTT. Among 98 progressors whose DYSOGTTs and NLOGTTs were
      synchronized for the time before diagnosis, despite higher glucose levels (P <
      0.01 at all time points) in the DYSOGTTs, 30- to 0-min C-peptide difference
      values changed little. Likewise, 30- to 0-min C-peptide difference values did not
      differ between TDOGTTs and subsequent (within 3 months) nondiabetic OGTTs in 55
      progressors. In contrast, as glucose levels increased overall from the first to
      last OGTTs before diagnosis (P < 0.001 at every time point, n = 207), 30- to 0
      min C-peptide difference values decreased (P < 0.001). CONCLUSIONS: Glucose
      levels fluctuate widely as they gradually increase overall with progression to
      type 1 diabetes. As glucose levels increase, the early C-peptide response
      declines. In contrast, glucose fluctuations are not related to the early C
      peptide response. This suggests that changes in insulin sensitivity underlie the
      glucose fluctuations.

PMID- 20682682
TI  - Central nervous system delivery of the antipsychotic olanzapine induces hepatic
      insulin resistance.
AB  - OBJECTIVE: Olanzapine (OLZ) is an atypical antipsychotic whose clinical efficacy
      is hampered by side effects including weight gain and diabetes. Recent evidence
      shows that OLZ alters insulin sensitivity independent of changes in body weight
      and composition. The present study addresses whether OLZ-induced insulin
      resistance is driven by its central actions. RESEARCH DESIGN AND METHODS: Sprague
      Dawley rats received an intravenous (OLZ-IV group) or intracerebroventricular
      (OLZ-ICV group) infusion of OLZ or vehicle. Glucose kinetics were assessed before
      (basal period) and during euglycemic-hyperinsulinemic clamp studies. RESULTS: OLZ
      IV caused a transient increase in glycemia and a higher rate of glucose
      appearance (R(a)) in the basal period. During the hyperinsulinemic clamp, the
      glucose infusion rate (GIR) required to maintain euglycemia and the rate of
      glucose utilization (R(d)) were decreased in OLZ-IV, whereas endogenous glucose
      production (EGP) rate was increased compared with vehicle-IV. Consistent with an
      elevation in EGP, the OLZ-IV group had higher hepatic mRNA levels for the enzymes
      glucose-6-phosphatase and phosphoenolpyruvate carboxykinase. Phosphorylation of
      hypothalamic AMP-activated protein kinase (AMPK) was increased in OLZ-IV rats
      compared with controls. Similarly, an intracerebroventricular infusion of OLZ
      resulted in a transient increase in glycemia as well as a higher R(a) in the
      basal period. During the hyperinsulinemic period, OLZ-ICV caused a decreased GIR,
      an increased EGP, but no change in R(d). Furthermore, OLZ-ICV rats had increased
      hepatic gluconeogenic enzymes and elevated hypothalamic neuropeptide-Y and agouti
      related protein mRNA levels. CONCLUSIONS: Acute central nervous system exposure
      to OLZ induces hypothalamic AMPK and hepatic insulin resistance, pointing to a
      hypothalamic site of action for the metabolic dysregulation of atypical
      antipsychotics.

PMID- 20682684
TI  - Acute stimulation of white adipocyte respiration by PKA-induced lipolysis.
AB  - OBJECTIVE: We examined the effect of beta-adrenergic receptor (betaAR) activation
      and cAMP-elevating agents on respiration and mitochondrial uncoupling in human
      adipocytes and probed the underlying molecular mechanisms. RESEARCH DESIGN AND
      METHODS: Oxygen consumption rate (OCR, aerobic respiration) and extracellular
      acidification rate (ECAR, anaerobic respiration) were examined in response to
      isoproterenol (ISO), forskolin (FSK), and dibutyryl-cAMP (DB), coupled with
      measurements of mitochondrial depolarization, lipolysis, kinase activities, and
      gene targeting or knock-down approaches. RESULTS: ISO, FSK, or DB rapidly
      increased oxidative and glycolytic respiration together with mitochondrial
      depolarization in human and mouse white adipocytes. The increase in OCR was
      oligomycin-insensitive and contingent on cAMP-dependent protein kinase A (PKA)
      induced lipolysis. This increased respiration and the uncoupling were blocked by
      inhibiting the mitochondrial permeability transition pore (PTP) and its
      regulator, BAX. Interestingly, compared with lean individuals, adipocytes from
      obese subjects exhibited reduced OCR and uncoupling capacity in response to ISO.
      CONCLUSIONS: Lipolysis stimulated by betaAR activation or other maneuvers that
      increase cAMP levels in white adipocytes acutely induces mitochondrial uncoupling
      and cellular energetics, which are amplified in the absence of scavenging BSA.
      The increase in OCR is dependent on PKA-induced lipolysis and is mediated by the
      PTP and BAX. Because this effect is reduced with obesity, further exploration of
      this uncoupling mechanism will be needed to determine its cause and consequences.

PMID- 20682685
TI  - Femoral adipose tissue may accumulate the fat that has been recycled as VLDL and
      nonesterified fatty acids.
AB  - OBJECTIVE: Gluteo-femoral, in contrast to abdominal, fat accumulation appears
      protective against diabetes and cardiovascular disease. Our objective was to test
      the hypothesis that this reflects differences in the ability of the two depots to
      sequester fatty acids, with gluteo-femoral fat acting as a longer-term "sink."
      RESEARCH DESIGN AND METHODS: A total of 12 healthy volunteers were studied after
      an overnight fast and after ingestion of a mixed meal. Blood samples were taken
      from veins draining subcutaneous femoral and abdominal fat and compared with
      arterialized blood samples. Stable isotope-labeled fatty acids were used to trace
      specific lipid fractions. In 36 subjects, adipose tissue blood flow in the two
      depots was monitored with (133)Xe. RESULTS: Blood flow increased in response to
      the meal in both depots, and these responses were correlated (r(s) = 0.44, P <
      0.01). Nonesterified fatty acid (NEFA) release was suppressed after the meal in
      both depots; it was lower in femoral fat than in abdominal fat (P < 0.01). Plasma
      triacylglycerol (TG) extraction by femoral fat was also lower than that by
      abdominal fat (P = 0.05). Isotopic tracers showed that the difference was in
      chylomicron-TG extraction. VLDL-TG extraction and direct NEFA uptake were similar
      in the two depots. CONCLUSIONS: Femoral fat shows lower metabolic fluxes than
      subcutaneous abdominal fat, but differs in its relative preference for extracting
      fatty acids directly from the plasma NEFA and VLDL-TG pools compared with
      chylomicron-TG.

PMID- 20682686
TI  - INS-1 cells undergoing caspase-dependent apoptosis enhance the regenerative
      capacity of neighboring cells.
AB  - OBJECTIVE: In diabetes, beta-cell mass is not static but in a constant process of
      cell death and renewal. Inactivating mutations in transcription factor 1 (tcf
      1)/hepatocyte nuclear factor1a (hnf1a) result in decreased beta-cell mass and
      HNF1A-maturity onset diabetes of the young (HNF1A-MODY). Here, we investigated
      the effect of a dominant-negative HNF1A mutant (DN-HNF1A) induced apoptosis on
      the regenerative capacity of INS-1 cells. RESEARCH DESIGN AND METHODS: DN-HNF1A
      was expressed in INS-1 cells using a reverse tetracycline-dependent
      transactivator system. Gene(s)/protein(s) involved in beta-cell regeneration were
      investigated by real-time quantitative RT-PCR, Western blotting, and
      immunohistochemistry. Pancreatic stone protein/regenerating protein (PSP/reg)
      serum levels in human subjects were detected by enzyme-linked immunosorbent
      assay. RESULTS: We detected a prominent induction of PSP/reg at the gene and
      protein level during DN-HNF1A-induced apoptosis. Elevated PSP/reg levels were
      also detected in islets of transgenic HNF1A-MODY mice and in the serum of HNF1A
      MODY patients. The induction of PSP/reg was glucose dependent and mediated by
      caspase activation during apoptosis. Interestingly, the supernatant from DN-HNF1A
      expressing cells, but not DN-HNF1A-expressing cells treated with zVAD.fmk, was
      sufficient to induce PSP/reg gene expression and increase cell proliferation in
      naive, untreated INS-1 cells. Further experiments demonstrated that annexin-V
      positive microparticles originating from apoptosing INS-1 cells mediated the
      induction of PSP/reg. Treatment with recombinant PSP/reg reversed the phenotype
      of DN-HNF1A-induced cells by stimulating cell proliferation and increasing
      insulin gene expression. CONCLUSIONS: Our results suggest that apoptosing INS-1
      cells shed microparticles that may stimulate PSP/reg induction in neighboring
      cells, a mechanism that may facilitate the recovery of beta-cell mass in HNF1A
      MODY.

PMID- 20682687
TI  - Common variants in 40 genes assessed for diabetes incidence and response to
      metformin and lifestyle intervention in the diabetes prevention program.
AB  - OBJECTIVE: Genome-wide association studies have begun to elucidate the genetic
      architecture of type 2 diabetes. We examined whether single nucleotide
      polymorphisms (SNPs) identified through targeted complementary approaches affect
      diabetes incidence in the at-risk population of the Diabetes Prevention Program
      (DPP) and whether they influence a response to preventive interventions. RESEARCH
      DESIGN AND METHODS: We selected SNPs identified by prior genome-wide association
      studies for type 2 diabetes and related traits, or capturing common variation in
      40 candidate genes previously associated with type 2 diabetes, implicated in
      monogenic diabetes, encoding type 2 diabetes drug targets or drug
      metabolizing/transporting enzymes, or involved in relevant physiological
      processes. We analyzed 1,590 SNPs for association with incident diabetes and
      their interaction with response to metformin or lifestyle interventions in 2,994
      DPP participants. We controlled for multiple hypothesis testing by assessing
      false discovery rates. RESULTS: We replicated the association of variants in the
      metformin transporter gene SLC47A1 with metformin response and detected nominal
      interactions in the AMP kinase (AMPK) gene STK11, the AMPK subunit genes PRKAA1
      and PRKAA2, and a missense SNP in SLC22A1, which encodes another metformin
      transporter. The most significant association with diabetes incidence occurred in
      the AMPK subunit gene PRKAG2 (hazard ratio 1.24, 95% CI 1.09-1.40, P = 7 * 10(
      4)). Overall, there were nominal associations with diabetes incidence at 85 SNPs
      and nominal interactions with the metformin and lifestyle interventions at 91 and
      69 mostly nonoverlapping SNPs, respectively. The lowest P values were consistent
      with experiment-wide 33% false discovery rates. CONCLUSIONS: We have identified
      potential genetic determinants of metformin response. These results merit
      confirmation in independent samples.

PMID- 20682688
TI  - Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study: common genetic variants
      in GCK and TCF7L2 are associated with fasting and postchallenge glucose levels in
      pregnancy and with the new consensus definition of gestational diabetes mellitus
      from the International Association of Diabetes and Pregnancy Study Groups.
AB  - OBJECTIVE: Common genetic variants in GCK and TCF7L2 are associated with higher
      fasting glucose and type 2 diabetes in nonpregnant populations. However, their
      associations with glucose levels from oral glucose tolerance tests (OGTTs) in
      pregnancy have not been assessed in a large sample. We hypothesized that these
      variants are associated with quantitative measures of glycemia in pregnancy.
      RESEARCH DESIGN AND METHODS: We analyzed the associations between variants
      rs1799884 (GCK) and rs7903146 (TCF7L2) and OGTT outcomes at 24-32 weeks'
      gestation in 3,811 mothers of European (U.K. and Australia) and 1,706 mothers of
      Asian (Thailand) ancestry from the HAPO cohort. We also tested associations with
      offspring birth anthropometrics. RESULTS: The maternal GCK variant was associated
      with higher fasting glucose in Europeans (P = 0.001) and Thais (P < 0.0001), 1-h
      glucose in Europeans (P = 0.001), and 2-h glucose in Thais (P = 0.005). It was
      also associated with higher European offspring birth weight, fat mass, and
      skinfold thicknesses (P < 0.05). The TCF7L2 variant was associated with all three
      maternal glucose outcomes (P = 0.03, P < 0.0001, and P < 0.0001 for fasting and 1
      h and 2-h glucose, respectively) in the Europeans but not in the Thais (P >
      0.05). In both populations, both variants were associated with higher odds of
      gestational diabetes mellitus according to the new International Association of
      Diabetes and Pregnancy Study Groups recommendations (P = 0.001-0.08).
      CONCLUSIONS: Maternal GCK and TCF7L2 variants are associated with glucose levels
      known to carry an increased risk of adverse pregnancy outcome in women without
      overt diabetes. Further studies will be important to determine the variance in
      maternal glucose explained by all known genetic variants.

PMID- 20682689
TI  - Obesity is a fibroblast growth factor 21 (FGF21)-resistant state.
AB  - OBJECTIVE: Fibroblast growth factor 21 (FGF21) is a key mediator of fatty acid
      oxidation and lipid metabolism. Pharmacological doses of FGF21 improve glucose
      tolerance, lower serum free fatty acids, and lead to weight loss in obese mice.
      Surprisingly, however, FGF21 levels are elevated in obese ob/ob and db/db mice
      and correlate positively with BMI in humans. However, the expected beneficial
      effects of endogenous FGF21 to increase glucose tolerance and reduce circulating
      triglycerides are absent in obesity. RESEARCH DESIGN AND METHODS: To test the
      hypothesis that obesity is a state of FGF21 resistance, we evaluated the response
      of obese mice to exogenous FGF21 administration. In doing this, we assessed the
      impact of diet-induced obesity on FGF21 signaling and resultant transcriptional
      events in the liver and white adipose tissue. We also analyzed the physiologic
      impact of FGF21 resistance by assessing serum parameters that are acutely
      regulated by FGF21. RESULTS: When obese mice are treated with FGF21, they display
      both a significantly attenuated signaling response as assessed by extracellular
      mitogen-activated protein kinase 1 and 2 (ERK1/2) phosphorylation as well as an
      impaired induction of FGF21 target genes, including cFos and EGR1. These effects
      were seen in both liver and fat. Similarly, changes in serum parameters such as
      the decline in glucose and free fatty acids are attenuated in FGF21-treated DIO
      mice. CONCLUSIONS: These data demonstrate that DIO mice have increased endogenous
      levels of FGF21 and respond poorly to exogenous FGF21. We therefore propose that
      obesity is an FGF21-resistant state.

PMID- 20682690
TI  - Antiobesity effect of eicosapentaenoic acid in high-fat/high-sucrose diet-induced
      obesity: importance of hepatic lipogenesis.
AB  - OBJECTIVE: Given the pleiotropic effect of eicosapentaenoic acid (EPA), it is
      interesting to know whether EPA is capable of improving obesity. Here we examined
      the anti-obesity effect of EPA in mice with two distinct models of obesity.
      RESEARCH DESIGN AND METHODS: Male C57BL/6J mice were fed a high-fat/high-sucrose
      diet (25.0% [w/w] fat, 32.5% [w/w] sucrose) (HF/HS group) or a high-fat diet
      (38.1% [w/w] fat, 8.5% [w/w] sucrose) (HF group) for 4-20 weeks. A total of 5%
      EPA was administered by partially substituting EPA for fat in the HF/HS + EPA and
      HF + EPA groups. RESULTS: Both the HF/HS and HF groups similarly developed
      obesity. EPA treatment strongly suppresses body weight gain and obesity-related
      hyperglycemia and hyperinsulinemia in HF/HS-fed mice (HF/HS + EPA group), where
      hepatic triglyceride content and lipogenic enzymes are increased. There is no
      appreciable effect of EPA on body weight in HF-fed mice (HF + EPA group) without
      enhanced expression of hepatic lipogenic enzymes. Moreover, EPA is capable of
      reducing hepatic triglyceride secretion and changing VLDL fatty acid composition
      in the HF/HS group. By indirect calorimetry analysis, we also found that EPA is
      capable of increasing energy consumption in the HF/HS + EPA group. CONCLUSIONS:
      This study is the first demonstration that the anti-obesity effect of EPA in
      HF/HS-induced obesity is associated with the suppression of hepatic lipogenesis
      and steatosis. Because the metabolic syndrome is often associated with hepatic
      lipogenesis and steatosis, the data suggest that EPA is suited for treatment of
      the metabolic syndrome.

PMID- 20682691
TI  - Hypothalamic AMP-activated protein kinase regulates glucose production.
AB  - OBJECTIVE: The fuel sensor AMP-activated protein kinase (AMPK) in the
      hypothalamus regulates energy homeostasis by sensing nutritional and hormonal
      signals. However, the role of hypothalamic AMPK in glucose production regulation
      remains to be elucidated. We hypothesize that bidirectional changes in
      hypothalamic AMPK activity alter glucose production. RESEARCH DESIGN AND METHODS:
      To introduce bidirectional changes in hypothalamic AMPK activity in vivo, we
      first knocked down hypothalamic AMPK activity in male Sprague-Dawley rats by
      either injecting an adenovirus expressing the dominant-negative form of AMPK (Ad
      DN AMPKalpha2 [D(157)A]) or infusing AMPK inhibitor compound C directly into the
      mediobasal hypothalamus. Next, we independently activated hypothalamic AMPK by
      delivering either an adenovirus expressing the constitutive active form of AMPK
      (Ad-CA AMPKalpha1(312) [T172D]) or the AMPK activator AICAR. The pancreatic
      (basal insulin)-euglycemic clamp technique in combination with the tracer
      dilution methodology was used to assess the impact of alternations in
      hypothalamic AMPK activity on changes in glucose kinetics in vivo. RESULTS:
      Injection of Ad-DN AMPK into the hypothalamus knocked down hypothalamic AMPK
      activity and led to a significant suppression of glucose production with no
      changes in peripheral glucose uptake during the clamps. In parallel, hypothalamic
      infusion of AMPK inhibitor compound C lowered glucose production as well.
      Conversely, molecular and pharmacological activation of hypothalamic AMPK negated
      the ability of hypothalamic nutrients to lower glucose production. CONCLUSIONS:
      These data indicate that changes in hypothalamic AMPK activity are sufficient and
      necessary for hypothalamic nutrient-sensing mechanisms to alter glucose
      production in vivo.

PMID- 20682692
TI  - Blockade of endothelial-mesenchymal transition by a Smad3 inhibitor delays the
      early development of streptozotocin-induced diabetic nephropathy.
AB  - OBJECTIVE: A multicenter, controlled trial showed that early blockade of the
      renin-angiotensin system in patients with type 1 diabetes and normoalbuminuria
      did not retard the progression of nephropathy, suggesting that other mechanism(s)
      are involved in the pathogenesis of early diabetic nephropathy (diabetic
      nephropathy). We have previously demonstrated that endothelial-mesenchymal
      transition (EndoMT) contributes to the early development of renal interstitial
      fibrosis independently of microalbuminuria in mice with streptozotocin (STZ)
      induced diabetes. In the present study, we hypothesized that blocking EndoMT
      reduces the early development of diabetic nephropathy. RESEARCH DESIGN AND
      METHODS: EndoMT was induced in a mouse pancreatic microvascular endothelial cell
      line (MMEC) in the presence of advanced glycation end products (AGEs) and in the
      endothelial lineage-traceble mouse line Tie2-Cre;Loxp-EGFP by administration of
      AGEs, with nonglycated mouse albumin serving as a control. Phosphorylated Smad3
      was detected by immunoprecipitation/Western blotting and confocal microscopy.
      Blocking studies using receptor for AGE siRNA and a specific inhibitor of Smad3
      (SIS3) were performed in MMECs and in STZ-induced diabetic nephropathy in Tie2
      Cre;Loxp-EGFP mice. RESULTS: Confocal microscopy and real-time PCR demonstrated
      that AGEs induced EndoMT in MMECs and in Tie2-Cre;Loxp-EGFP mice.
      Immunoprecipitation/Western blotting showed that Smad3 was activated by AGEs but
      was inhibited by SIS3 in MMECs and in STZ-induced diabetic nephropathy. Confocal
      microscopy and real-time PCR further demonstrated that SIS3 abrogated EndoMT,
      reduced renal fibrosis, and retarded progression of nephropathy. CONCLUSIONS:
      EndoMT is a novel pathway leading to early development of diabetic nephropathy.
      Blockade of EndoMT by SIS3 may provide a new strategy to retard the progression
      of diabetic nephropathy and other diabetes complications.

PMID- 20682693
TI  - Increased reactive oxygen species production and lower abundance of complex I
      subunits and carnitine palmitoyltransferase 1B protein despite normal
      mitochondrial respiration in insulin-resistant human skeletal muscle.
AB  - OBJECTIVE: The contribution of mitochondrial dysfunction to skeletal muscle
      insulin resistance remains elusive. Comparative proteomics are being applied to
      generate new hypotheses in human biology and were applied here to isolated
      mitochondria to identify novel changes in mitochondrial protein abundance present
      in insulin-resistant muscle. RESEARCH DESIGN AND METHODS: Mitochondria were
      isolated from vastus lateralis muscle from lean and insulin-sensitive individuals
      and from obese and insulin-resistant individuals who were otherwise healthy.
      Respiration and reactive oxygen species (ROS) production rates were measured in
      vitro. Relative abundances of proteins detected by mass spectrometry were
      determined using a normalized spectral abundance factor method. RESULTS: NADH-
      and FADH(2)-linked maximal respiration rates were similar between lean and obese
      individuals. Rates of pyruvate and palmitoyl-DL-carnitine (both including malate)
      ROS production were significantly higher in obesity. Mitochondria from obese
      individuals maintained higher (more negative) extramitochondrial ATP free energy
      at low metabolic flux, suggesting that stronger mitochondrial thermodynamic
      driving forces may underlie the higher ROS production. Tandem mass spectrometry
      identified protein abundance differences per mitochondrial mass in insulin
      resistance, including lower abundance of complex I subunits and enzymes involved
      in the oxidation of branched-chain amino acids (BCAA) and fatty acids (e.g.,
      carnitine palmitoyltransferase 1B). CONCLUSIONS: We provide data suggesting
      normal oxidative capacity of mitochondria in insulin-resistant skeletal muscle in
      parallel with high rates of ROS production. Furthermore, we show specific
      abundance differences in proteins involved in fat and BCAA oxidation that might
      contribute to the accumulation of lipid and BCAA frequently associated with the
      pathogenesis of insulin resistance.

PMID- 20682695
TI  - Antiobesity and antihyperglycemic effects of ginsenoside Rb1 in rats.
AB  - OBJECTIVE: Obesity and type 2 diabetes are national and worldwide epidemics.
      Because currently available antiobesity and antidiabetic drugs have limited
      efficacy and/or safety concerns, identifying new medicinal agents, such as
      ginsenoside Rb1 (Rb1) as reported here, offers exciting possibilities for future
      development of successful antiobesity and antidiabetic therapies. RESEARCH DESIGN
      AND METHODS: Changes in feeding behavior after acute intraperitoneal
      administration of Rb1 and the effects of intraperitoneal Rb1 for 4 weeks on body
      weight, energy expenditure, and glucose tolerance in high-fat diet (HFD)-induced
      obese rats were assessed. We also examined the effects of Rb1 on signaling
      pathways and neuropeptides in the hypothalamus. RESULTS: Acute intraperitoneal
      Rb1 dose-dependently suppressed food intake without eliciting signs of toxicity.
      This inhibitory effect on feeding may be mediated by central mechanisms because
      Rb1 stimulated c-Fos expression in brain areas involved in energy homeostasis.
      Consistent with this, Rb1 activated the phosphatidylinositol 3-kinase/Akt
      signaling pathway and inhibited NPY gene expression in the hypothalamus. Four
      week administration of Rb1 significantly reduced food intake, body weight gain,
      and body fat content and increased energy expenditure in HFD-induced obese rats.
      Rb1 also significantly decreased fasting blood glucose and improved glucose
      tolerance, and these effects were greater than those observed in pair-fed rats,
      suggesting that although Rb1's antihyperglycemic effect is partially attributable
      to reduced food intake and body weight; there may be additional effects of Rb1 on
      glucose homeostasis. CONCLUSIONS: These results identify Rb1 as an antiobesity
      and antihyperglycemic agent.

PMID- 20682694
TI  - Insulin transactivator MafA regulates intrathymic expression of insulin and
      affects susceptibility to type 1 diabetes.
AB  - OBJECTIVE: Tissue-specific self-antigens are ectopically expressed within the
      thymus and play an important role in the induction of central tolerance. Insulin
      is expressed in both pancreatic islets and the thymus and is considered to be the
      primary antigen for type 1 diabetes. Here, we report the role of the insulin
      transactivator MafA in the expression of insulin in the thymus and susceptibility
      to type 1 diabetes. RESEARCH DESIGN AND METHODS: The expression profiles of
      transcriptional factors (Pdx1, NeuroD, Mafa, and Aire) in pancreatic islets and
      the thymus were examined in nonobese diabetic (NOD) and control mice. Thymic Ins2
      expression and serum autoantibodies were examined in Mafa knockout mice.
      Luciferase reporter assay was performed for newly identified polymorphisms of
      mouse Mafa and human MAFA. A case-control study was applied for human MAFA
      polymorphisms. RESULTS: Mafa, Ins2, and Aire expression was detected in the
      thymus. Mafa expression was lower in NOD thymus than in the control and was
      correlated with Ins2 expression. Targeted disruption of MafA reduced thymic Ins2
      expression and induced autoantibodies against pancreatic islets. Functional
      polymorphisms of MafA were newly identified in NOD mice and humans, and
      polymorphisms of human MAFA were associated with susceptibility to type 1
      diabetes but not to autoimmune thyroid disease. CONCLUSIONS: These data indicate
      that functional polymorphisms of MafA are associated with reduced expression of
      insulin in the thymus and susceptibility to type 1 diabetes in the NOD mouse as
      well as human type 1 diabetes.

PMID- 20682696
TI  - Downregulation of AMPK accompanies leucine- and glucose-induced increases in
      protein synthesis and insulin resistance in rat skeletal muscle.
AB  - OBJECTIVE: Branched-chain amino acids, such as leucine and glucose, stimulate
      protein synthesis and increase the phosphorylation and activity of the mammalian
      target of rapamycin (mTOR) and its downstream target p70S6 kinase (p70S6K). We
      examined in skeletal muscle whether the effects of leucine and glucose on these
      parameters and on insulin resistance are mediated by the fuel-sensing enzyme AMP
      activated protein kinase (AMPK). RESEARCH DESIGN AND METHODS: Rat extensor
      digitorum longus (EDL) muscle was incubated with different concentrations of
      leucine and glucose with or without AMPK activators. Muscle obtained from glucose
      infused rats was also used as a model. RESULTS: In the EDL, incubation with 100
      or 200 MUmol/l leucine versus no added leucine suppressed the activity of the
      alpha2 isoform of AMPK by 50 and 70%, respectively, and caused concentration
      dependent increases in protein synthesis and mTOR and p70S6K phosphorylation.
      Very similar changes were observed in EDL incubated with 5.5 or 25 mmol/l versus
      no added glucose and in muscle of rats infused with glucose in vivo. Incubation
      of the EDL with the higher concentrations of both leucine and glucose also caused
      insulin resistance, reflected by a decrease in insulin-stimulated Akt
      phosphorylation. Coincubation with the AMPK activators AICAR and alpha-lipoic
      acid substantially prevented all of those changes and increased the
      phosphorylation of specific sites of mTOR inhibitors raptor and tuberous
      sclerosis complex 2 (TSC2). In contrast, decreases in AMPK activity induced by
      leucine and glucose were not associated with a decrease in raptor or TSC2
      phosphorylation. CONCLUSIONS: The results indicate that both leucine and glucose
      modulate protein synthesis and mTOR/p70S6 and insulin signaling in skeletal
      muscle by a common mechanism. They also suggest that the effects of both
      molecules are associated with a decrease in AMPK activity and that AMPK
      activation prevents them.

PMID- 20682697
TI  - Detailed physiological characterization of the development of type 2 diabetes in
      Hispanic women with prior gestational diabetes mellitus.
AB  - OBJECTIVE: To identify physiological and clinical variables associated with
      development of type 2 diabetes up to 12 years after pregnancies complicated by
      gestational diabetes. RESEARCH DESIGN AND METHODS: Seventy-two islet cell
      antibody-negative nondiabetic Hispanic women had oral (oGTT) and intravenous
      (ivGTT) glucose tolerance tests, glucose clamps, and body composition assessed
      between 15 and 30 months after pregnancies complicated by gestational diabetes
      mellitus (GDM). They returned for oGTTs at 15-month intervals until they dropped
      out, developed diabetes, or reached 12 years postpartum. Cox regression analysis
      was used to identify baseline predictors and changes during follow-up that were
      associated with development of type 2 diabetes. RESULTS: At baseline, relatively
      low insulin sensitivity, insulin response, and beta-cell compensation for insulin
      resistance were independently associated with development of diabetes. During
      follow-up, weight and fat gain and rates of decline in beta-cell compensation
      were significantly associated with diabetes, while additional pregnancy and use
      of progestin-only contraception were marginally associated with diabetes risk.
      CONCLUSIONS: In Hispanic women, GDM represents detection of a chronic disease
      process characterized by falling beta-cell compensation for chronic insulin
      resistance. Women who are farthest along at diagnosis and/or deteriorating most
      rapidly are most likely to develop type 2 diabetes within 12 years after the
      index pregnancy. Weight gain, additional pregnancy, and progestin-only
      contraception are potential modifiable factors that increase diabetes risk.

PMID- 20682698
TI  - Identification of a serum-induced transcriptional signature associated with type
      1 diabetes in the BioBreeding rat.
AB  - OBJECTIVE: Inflammatory mediators associated with type 1 diabetes are dilute and
      difficult to measure in the periphery, necessitating development of more
      sensitive and informative biomarkers for studying diabetogenic mechanisms,
      assessing preonset risk, and monitoring therapeutic interventions. RESEARCH
      DESIGN AND METHODS: We previously utilized a novel bioassay in which human type 1
      diabetes sera were used to induce a disease-specific transcriptional signature in
      unrelated, healthy peripheral blood mononuclear cells (PBMCs). Here, we apply
      this strategy to investigate the inflammatory state associated with type 1
      diabetes in biobreeding (BB) rats. RESULTS: Consistent with their common
      susceptibility, sera of both spontaneously diabetic BB DRlyp/lyp and diabetes
      inducible BB DR+/+ rats induced transcription of cytokines, immune receptors, and
      signaling molecules in PBMCs of healthy donor rats compared with control sera.
      Like the human type 1 diabetes signature, the DRlyp/lyp signature, which is
      associated with progression to diabetes, was differentiated from that of the
      DR+/+ by induction of many interleukin (IL)-1-regulated genes. Supplementing
      cultures with an IL-1 receptor antagonist (IL-1Ra) modulated the DRlyp/lyp
      signature (P < 10(-6)), while administration of IL-1Ra to DRlyp/lyp rats delayed
      onset (P = 0.007), and sera of treated animals did not induce the characteristic
      signature. Consistent with the presence of immunoregulatory cells in DR+/+ rats
      was induction of a signature possessing negative regulators of transcription and
      inflammation. CONCLUSIONS: Paralleling our human studies, serum signatures in BB
      rats reflect processes associated with progression to type 1 diabetes.
      Furthermore, these studies support the potential utility of this approach to
      detect changes in the inflammatory state during therapeutic intervention.

PMID- 20682699
TI  - Mannan-binding lectin deficiency results in unusual antibody production and
      excessive experimental colitis in response to mannose-expressing mild gut
      pathogens.
AB  - BACKGROUND: In Crohn's disease (CD) the deficiency of mannan-binding lectin (MBL)
      is associated with an increased prevalence of anti-Saccharomyces cerevisiae
      antibodies (ASCA) and with complicated phenotypes of the disease. However, the
      role of MBL in intestinal inflammation is currently unclear. A study was
      undertaken to analyse local MBL expression in human intestine and the
      consequences of MBL deficiency in experimental colitis and yeast infection.
      METHODS: ASCA were measured by ELISA. MBL was assessed by ELISA and quantitative
      PCR. Wild type and MBL-deficient mice were administered dextran sulfate sodium
      (DSS) in the presence or absence of viable Candida albicans or adhesive invasive
      Escherichia coli (AIEC). Mice were infected with C albicans to assess generation
      of anti-yeast mannan antibodies. RESULTS: MBL expression was virtually
      undetectable in the intestinal mucosa of both healthy controls and patients with
      CD, irrespective of macroscopic inflammation, indicating that systemic MBL must
      be responsible for the reduced risk of complicated disease in MBL-competent
      patients with CD. MBL-deficient mice showed enhanced DSS colitis upon oral
      challenge with C albicans or AIEC. C albicans could be recovered from the kidneys
      of colitic/C albicans-fed MBL-deficient, but not wild type mice. Infection with C
      albicans induced high titres of anti-C albicans mannan IgM and IgG in MBL
      deficient mice but only a modest and transient IgM response with no class switch
      to IgG in wild type mice. Cross-reactive ASCA IgM continuously increased in MBL
      deficient mice but rapidly declined after transient induction in wild type mice.
      In MBL-deficient mice, increased C albicans dissemination correlated with reduced
      early retention in the circulation. CONCLUSIONS: These results suggest that
      systemic MBL helps to prevent excessive inflammation upon access of normally mild
      pathogens across the damaged intestinal epithelium. Lack of this innate defence
      promotes antibody responses with cross-reactive potential against common mannan
      epitopes. These interpretations are compatible with the increased prevalence of
      ASCA and complicated disease phenotypes in MBL-deficient patients with CD.

PMID- 20682701
TI  - The genetic basis of colorectal cancer in a population-based incident cohort with
      a high rate of familial disease.
AB  - BACKGROUND AND AIMS: Colorectal cancer (CRC) is the second most frequent cancer
      in developed countries. Newfoundland has the highest incidence of CRC in Canada
      and the highest rate of familial CRC yet reported in the world. To determine the
      impact of mutations in known CRC susceptibility genes and the contribution of the
      known pathways to the development of hereditary CRC, an incident cohort of 750
      patients with CRC (708 different families) from the Newfoundland population was
      studied. METHODS: Microsatellite instability (MSI) testing was performed on
      tumours, together with immunohistochemistry analysis for mismatch repair (MMR)
      genes. Where indicated, DNA sequencing and multiplex ligation-dependent probe
      amplifications of MMR genes and APC was undertaken. DNA from all patients was
      screened for MUTYH mutations. The presence of the BRAF variant, p.V600E, and of
      MLH1 promoter methylation was also tested in tumours. RESULTS: 4.6% of patients
      fulfilled the Amsterdam criteria (AC), and an additional 44.6% fulfilled the
      revised Bethesda criteria. MSI-high (MSI-H) was observed in 10.7% (n=78) of 732
      tumours. In 3.6% (n=27) of patients, CRC was attributed to 12 different inherited
      mutations in six known CRC-related genes associated with chromosomal instability
      or MSI pathways. Seven patients (0.9%) carried a mutation in APC or biallelic
      mutations in MUTYH. Of 20 patients (2.7%) with mutations in MMR genes, 14 (70%)
      had one of two MSH2 founder mutations. 17 of 28 (61%) AC families did not have a
      genetic cause identified, of which 15 kindreds fulfilled the criteria for
      familial CRC type X (FCCTX). CONCLUSIONS: Founder mutations accounted for only
      2.1% of cases and this was insufficient to explain the high rate of familial CRC.
      Many of the families classified as FCCTX may have highly penetrant mutations
      segregating in a Mendelian-like manner. These families will be important for
      identifying additional CRC susceptibility loci.

PMID- 20682702
TI  - Reproducibility of [11C]choline-positron emission tomography and effect of
      trastuzumab.
AB  - PURPOSE: This study sought to evaluate the reproducibility of [(11)C]choline
      positron emission tomography and the effect of trastuzumab in breast cancer.
      EXPERIMENTAL DESIGN: Twenty-one patients with newly diagnosed and recurrent
      breast cancer stage II-IV had a baseline dynamic [(11)C]choline-PET scan, 10
      patients had a second [(11)C]choline-PET scan to examine reproducibility, and 6
      patients had a second scan within a month after trastuzumab. Analysis of
      [(11)C]choline uptake was measured as the semiquantitative standardized uptake
      value at 30 and 60 minutes (SUV(30) and SUV(60)), and quantitatively as the net
      irreversible retention of the radiotracer at steady-state (Ki) and plasma to
      tissue exchange at 60 minutes (IRF60min). RESULTS: Breast tumor lesions in all
      patients were visualized by [(11)C]choline PET. The difference in tumor versus
      normal tissue uptake was significant for SUV(30), SUV(60), Ki, and IRF60 minutes
      (Wilcoxon P < 0.0001). At 60 minutes postinjection, 15.1 +/- 2.16% of plasma
      radioactivity was due to unmetabolized [(11)C]choline radioactivity.
      [(11)C]Choline uptake was reproducible in breast tumor lesions (r(2) = 0.9 for
      SUV, 0.9 for Ki, and 0.8 for IRF60). Early responses to trastuzumab measured by
      [(11)C]choline-PET were significant in three lesions occurring in two patients
      who responded clinically. CONCLUSIONS: [(11)C]Choline-PET uptake variables can be
      reproducibly assessed. Initial studies show that trastuzumab decreases
      [(11)C]choline uptake.

PMID- 20682703
TI  - Fluorescence-based codetection with protein markers reveals distinct cellular
      compartments for altered MicroRNA expression in solid tumors.
AB  - PURPOSE: High-throughput profiling experiments have linked altered expression of
      microRNAs (miRNA) to different types of cancer. Tumor tissues are a heterogeneous
      mixture of not only cancer cells, but also supportive and reactive tumor
      microenvironment elements. To clarify the clinical significance of altered miRNA
      expression in solid tumors, we developed a sensitive fluorescence-based in situ
      hybridization (ISH) method to visualize miRNA accumulation within individual
      cells in formalin-fixed, paraffin-embedded tissue specimens. This ISH method was
      implemented to be compatible with routine clinical immunohistochemical (IHC)
      assays to enable the detection of miRNAs and protein markers in the same tissue
      section for colocalization and functional studies. EXPERIMENTAL DESIGN: We used
      this combined ISH/IHC assay to study a subset of cancer-associated miRNAs,
      including miRNAs frequently detected at low (miR-34a and miR-126) and high (miR
      21 and miR-155) levels, in a panel of breast, colorectal, lung, pancreas, and
      prostate carcinomas. RESULTS: Despite the distinct histopathologic alterations of
      each particular cancer type, general trends emerged that pinpointed distinct
      source cells of altered miRNA expression. Although altered expressions of miR-21
      and miR-34a were manifested within cancer cells, those of miR-126 and miR-155
      were predominantly confined to endothelial cells and immune cells, respectively.
      These results suggest a heterogeneous participation of miRNAs in carcinogenesis
      by intrinsically affecting cancer cell biology or by modulating stromal,
      vascular, and immune responses. CONCLUSIONS: We described a rapid and sensitive
      multicolor ISH/IHC assay and showed that it could be broadly applied as an
      investigational tool to better understand the etiologic relevance of altered
      miRNA expression in cancer.

PMID- 20682704
TI  - Biological evidence for dual antiangiogenic-antiaromatase activity of the VEGFR
      inhibitor PTK787/ZK222584 in vivo.
AB  - PURPOSE: Targeting vascular endothelial growth factor (VEGF) and estrogen
      receptor signaling pathways concomitantly may enhance benefit in estrogen
      receptor-positive breast cancer. We had shown previously that the VEGF receptor
      tyrosine kinase inhibitor PTK787/ZK222584 (PTK/ZK) is a competitive aromatase
      inhibitor in vitro. Here we investigated (a) whether PTK/ZK shows both
      antiangiogenic and antiaromatase inhibitory properties in vivo, and (b) whether
      the combination of PTK/ZK and letrozole is superior to letrozole alone.
      EXPERIMENTAL DESIGN: Estrogen-dependent human breast cancer cells engineered to
      express aromatase (MCF7 AROM 1 and BT474 AROM) were used. Mice were treated with
      vehicle, PTK/ZK (25, 50, or 100 mg/kg), letrozole, or PTK/ZK in combination with
      letrozole. RESULTS: In MCF7 AROM 1 tumors, all treatments induced growth
      suppression and were associated with a reduction in cell turnover index, a
      composite measurement of both proliferation and apoptosis. PTK/ZK significantly
      reduced vessel density. Whereas letrozole caused tumor regression, PTK/ZK
      stabilized tumor volumes. The growth suppressive and antiangiogenic effects of
      PTK/ZK were confirmed in BT474 AROM xenografts. The addition of PTK/ZK did not
      enhance the growth-suppressive effects of letrozole. However, PTK/ZK decreased
      progesterone receptor (PgR) and TFF1 expression and uterine weight, indicating
      that PTK/ZK decreases 17beta-estradiol (E2) signaling in vivo. CONCLUSION: The
      VEGF receptor inhibitor PTK/ZK showed effects on E2-dependent gene expression
      consistent with aromatase inhibition as well as antiangiogenesis in xenograft
      models of breast cancer. The combination with letrozole was not superior to
      letrozole alone. Overall, these results provide further support for a potential
      therapeutic approach of dual inhibition of VEGF and E2 signaling using a single
      agent.

PMID- 20682705
TI  - Combination therapy of bortezomib with novel targeted agents: an emerging
      treatment strategy.
AB  - Clinical trials evaluating combinations of targeted agents with bortezomib, the
      first-in-class proteasome inhibitor, have been initiated, with the objective of
      enhancing its single agent activity in hematologic malignancies (myeloma, mantle
      cell lymphoma), as well as expanding its efficacy in solid tumors. In most cases,
      preclinical studies have provided a supportive rationale for designing these
      doublet combination studies. Novel, small molecule-targeted agents being
      investigated with bortezomib in clinical trials include protein deacetylase
      inhibitors, kinase inhibitors, farnesyltransferase inhibitors, heat-shock protein
      90 inhibitors, pan-Bcl-2 family inhibitors, and other classes of targeted
      inhibitors. Preliminary clinical data, available from a number of ongoing trials,
      suggest that most of these combinations are well tolerated and some have
      promising clinical efficacy that will require subsequent confirmation.
      Translational studies, conducted as part of the trials, may provide important
      insights into the putative mechanism of action delineated by preclinical studies
      of the combinations. The emergence of novel proteasome inhibitors may also expand
      the opportunities for optimizing these combination therapies. There is potential
      for an increasingly broad clinical trials program to investigate this therapeutic
      approach in a range of tumor types, as well as to consider additional agents in
      sequence or in combination.

PMID- 20682706
TI  - Accumulation of foxp3+ T regulatory cells in draining lymph nodes correlates with
      disease progression and immune suppression in colorectal cancer patients.
AB  - PURPOSE: To assess the relation of Foxp3(+) regulatory T cells (Treg) in tumor
      draining lymph nodes (TDLNs) with tumor progression and immune suppression in
      colorectal cancer (CRC). EXPERIMENTAL DESIGN: Flow cytometry was used to analyze
      the densities of Tregs in lymphocytes of TDLNs, peripheral blood, and tumors from
      34 patients with CRC. The frequency of Tregs was compared and evaluated for the
      association with disease stage. The effect of Tregs on the function of CD8(+) T
      cells was investigated by IFN-gamma production. RESULTS: The density of Foxp3(+)
      Tregs in TDLNs was dramatically higher than that in peripheral blood lymphocytes,
      but significantly lower than that in tumor-infiltrating lymphocytes. Importantly,
      the frequency of Foxp3(+) Tregs in TDLNs, rather than that in tumors and
      peripheral blood, was positively correlated with disease stage. In addition, the
      functions of CD8(+) T cells were impaired in TDLNs compared with peripheral blood
      lymphocytes and were restored after Treg depletion. CONCLUSIONS: Foxp3(+) Tregs
      in TDLNs are more correlated with disease progression and potentially influence
      CD8(+) T-cell functions. This study suggests that the frequency of Tregs in TDLNs
      may provide a valuable prognostic tool in the treatment of CRC.

PMID- 20682707
TI  - The oncoprotein SF2/ASF promotes non-small cell lung cancer survival by enhancing
      survivin expression.
AB  - PURPOSE: SF2/ASF is a splicing factor recently described as an oncoprotein. In
      the present work, we examined the role of SF2/ASF in human non-small cell lung
      cancer (NSCLC) and analyzed the molecular mechanisms involved in SF2/ASF-related
      carcinogenesis. EXPERIMENTAL DESIGN: SF2/ASF protein levels were analyzed in 81
      NSCLC patients by immunohistochemistry. SF2/ASF downregulation cellular models
      were generated using small interfering RNAs, and the effects on proliferation and
      apoptosis were evaluated. Survivin and SF2/ASF expression in lung tumors was
      analyzed by Western blot and immunohistochemistry. Survival curves and log-rank
      test were used to identify the association between the expression of the proteins
      and time to progression. RESULTS: Overexpression of SF2/ASF was found in most
      human primary NSCLC tumors. In vitro downregulation of SF2/ASF induced apoptosis
      in NSCLC cell lines. This effect was associated with a reduction in the
      expression of survivin, an antiapoptotic protein widely upregulated in cancer. In
      fact, SF2/ASF specifically bound survivin mRNA and enhanced its translation, via
      a mammalian target of rapamycin complex 1 (mTORC1) pathway-dependent mechanism,
      through the phosphorylation and inactivation of the translational repressor 4E
      BP1. Moreover, SF2/ASF promoted the stability of survivin mRNA. A strong
      correlation was observed between the expression of SF2/ASF and survivin in tumor
      biopsies from NSCLC patients, supporting the concept that survivin expression
      levels are controlled by SF2/ASF. Furthermore, combined expression of these
      proteins was associated with prognosis. CONCLUSION: This study provides novel
      data on the mTORC1- and survivin-dependent mechanisms of SF2/ASF-related
      carcinogenic potential, and shows that SF2/ASF and survivin expression is
      involved in NSCLC progression.

PMID- 20682708
TI  - An open-label, phase I study of the polo-like kinase-1 inhibitor, BI 2536, in
      patients with advanced solid tumors.
AB  - PURPOSE: This phase I, open-label, dose-escalation study investigated the maximum
      tolerated dose (MTD) of BI 2536, a small-molecule polo-like kinase (Plk)-1
      inhibitor, in two treatment schedules in patients with advanced solid tumors.
      Secondary objectives included evaluation of safety, efficacy, and
      pharmacokinetics. EXPERIMENTAL DESIGN: Patients received a single i.v. dose of BI
      2536 as a 1-hour infusion on days 1 and 8 or a single 24-hour infusion on day 1
      of each 21-day treatment course. MTD determination was based on dose-limiting
      toxicities. RESULTS: Forty-four and 26 patients received each treatment schedule,
      respectively. The MTD of BI 2536 in the day 1 and 8 schedule was 100 mg per
      administration (200 mg per course). The MTD for the second dosing schedule was
      not determined; a 225-mg dose was well tolerated. The most frequently reported
      treatment-related nonhematologic adverse events were gastrointestinal events and
      fatigue. Hematotoxicity as the most relevant side effect was similar in both
      schedules; neutropenia grades 3 and 4 were observed in 16 patients (36.4%) of the
      day 1 and 8 schedule and 13 patients (50%) of the 24-hour infusion. Fourteen
      patients (32%) treated in the day 1 and 8 dosing schedule had a best overall
      response of stable disease. Plasma concentrations of BI 2536 increased dose
      proportionally, with no relevant accumulation of exposure in the day 1 and 8
      dosing schedule. The average terminal half-life was 50 hours. CONCLUSIONS: BI
      2536 administered in either treatment schedule has adequate safety in patients
      with advanced solid tumors, warranting further clinical investigation of polo
      like kinase-1 inhibitors.

PMID- 20682709
TI  - X-linked inhibitor of apoptosis: a chemoresistance factor or a hollow promise.
AB  - The X-linked inhibitor of apoptosis (XIAP) is the only cellular protein that has
      evolved to potently inhibit the enzymatic activity of mammalian caspases and
      promotes resistance to apoptosis. Given its role in apoptosis and its frequently
      elevated expression in malignant cells, XIAP has garnered the most attention as a
      promising therapeutic target in cancer to overcome drug resistance. Accordingly,
      XIAP is thought to render tumor cells resistant to chemotherapy through its
      ability to inhibit caspases, and it is on this basis that XIAP has been proposed
      as an important adverse biomarker for chemoresistance in cancer patients. Here,
      the current understanding of the role of XIAP in cancer is reviewed. Further, the
      notion is explored that the elevated XIAP expression frequently observed in
      malignant tissues is, at least, not exclusively responsible for the resistance of
      tumor cells to conventional therapeutic treatment; rather, the function of XIAP
      seems to be conducive to the process of malignant transformation and/or
      progression.

PMID- 20682710
TI  - Inhibition of hypoxia inducible factor-1alpha by dihydroxyphenylethanol, a
      product from olive oil, blocks microsomal prostaglandin-E synthase-1/vascular
      endothelial growth factor expression and reduces tumor angiogenesis.
AB  - PURPOSE: 2-(3,4-dihydroxyphenil)-ethanol (DPE), a polyphenol present in olive
      oil, has been found to attenuate the growth of colon cancer cells, an effect
      presumably related to its anti-inflammatory activity. EXPERIMENTAL DESIGN: To
      further explore the effects of DPE on angiogenesis and tumor growth we
      investigated the in vivo efficacy of DPE in a HT-29 xenograft model and in vitro
      activities in colon cancer cells exposed to interleukin-1beta (IL-1beta) and
      prostaglandin E-2 (PGE-2). RESULTS: DPE (10 mg/kg/day for 14 days) inhibited
      tumor growth, reducing vessel lumina and blood perfusion to tumor, and diminished
      expression of hypoxia inducible factor-1alpha (HIF-1alpha), vascular endothelial
      growth factor (VEGF), and microsomal prostaglandin-E synthase-1 (mPGEs-1). In
      vitro, DPE (100 mumol/L) neither affected cell proliferation nor induced
      apoptosis in HT-29 and WiDr cells. DPE prevented the IL-1beta-mediated increase
      of mPGEs-1 expression and PGE-2 generation, as it did the silencing of HIF
      1alpha. Moreover, DPE blocked mPGEs-1-dependent expression of VEGF and inhibited
      endothelial sprouting induced by tumor cells in a coculture system. PGE-2
      triggers a feed-forward loop involving HIF-1alpha, which impinges on mPGEs-1 and
      VEGF expression, events prevented by DPE via extracellular signal-related kinase
      1/2. The reduction of PGE-2 and VEGF levels, caused by DPE, was invariably
      associated with a marked decrease in HIF-1alpha expression and activity,
      independent of proteasome activity, indicating that the DPE effects on tumor
      growth and angiogenesis are dependent on the inhibition of HIF-1alpha
      translation. CONCLUSIONS: We show that the in vivo DPE antitumor effect is
      associated with anti-inflammatory and antiangiogenic activities resulting from
      the downregulation of the HIF-1alpha/mPGEs-1/VEGF axis.

PMID- 20682711
TI  - SMAD4 immunohistochemistry reflects genetic status in juvenile polyposis
      syndrome.
AB  - PURPOSE: Juvenile polyposis syndrome (JPS) can be caused by a germline defect of
      the SMAD4 gene. Somatic inactivation of SMAD4 occurs in pancreatic and colorectal
      cancers and is reflected by loss of SMAD4 immunohistochemistry. Here, SMAD4
      immunohistochemistry as a marker of SMAD4 gene status and the role of SMAD4 in
      the adenoma-carcinoma sequence in neoplastic progression in JPS are studied.
      EXPERIMENTAL DESIGN: Twenty polyps with a SMAD4 germline defect and 38 control
      polyps were studied by SMAD4 immunohistochemistry. Inactivation of the SMAD4 wild
      type allele was studied in dysplastic epithelium and in areas with aberrant SMAD4
      expression. APC, beta-catenin, p53, and K-ras were studied to evaluate the
      adenoma-carcinoma sequence. RESULTS: Nine of 20 polyps with a SMAD4 germline
      defect showed loss of epithelial SMAD4 expression. Loss of heterozygosity of
      SMAD4 was found in five polyps and a somatic stop codon mutation was found in two
      polyps without loss of heterozygosity. Remarkably, somatic inactivation of
      epithelial SMAD4 did not always coincide with dysplasia and aberrant p53 staining
      was found in four of six dysplastic polyps with normal SMAD4 staining. One K-ras
      mutation was found in nine juvenile polyps with dysplasia. No evidence for Wnt
      activation was found. CONCLUSIONS: SMAD4 immunohistochemistry mirrors genetic
      status and provides a specific adjunct in the molecular diagnosis of JPS.
      However, epithelial SMAD4 inactivation is not required for polyp formation and is
      not obligatory for neoplastic progression in JPS. Instead, different routes to
      neoplasia in JPS caused by germline SMAD4 mutation seem to be operative,
      including somatic loss of SMAD4 and p53 inactivation without somatic loss of
      SMAD4.

PMID- 20682712
TI  - Gene array and fluorescence in situ hybridization biomarkers of activity of
      saracatinib (AZD0530), a Src inhibitor, in a preclinical model of colorectal
      cancer.
AB  - PURPOSE: To evaluate the efficacy of saracatinib (AZD0530), an oral Src
      inhibitor, in colorectal cancer (CRC) and to identify biomarkers that predict
      antitumor activity. EXPERIMENTAL DESIGN: Twenty-three CRC cell lines were exposed
      to saracatinib, and baseline gene expression profiles of three sensitive and
      eight resistant cell lines in vitro and in vivo were used to predict saracatinib
      sensitivity in an independent group of 10 human CRC explant tumors using the gene
      array K-Top Scoring Pairs (K-TSP) method. In addition, fluorescence in situ
      hybridization (FISH) and immunoblotting determined both Src gene copy number and
      activation of Src, respectively. RESULTS: Two of 10 explant tumors were
      determined to be sensitive to saracatinib. The K-TSP classifier (TOX>GLIS2,
      TSPAN7>BCAS4, and PARD6G>NXN) achieved 70% (7 of 10) accuracy on the test set.
      Evaluation of Src gene copy number by FISH showed a trend toward significance (P
      = 0.066) with respect to an increase in Src gene copy and resistance to
      saracatinib. Tumors sensitive to saracatinib showed an increase in the activation
      of Src and FAK when compared with resistant tumors. CONCLUSIONS: Saracatinib
      significantly decreased tumor growth in a subset of CRC cell lines and explants.
      A K-TSP classifier (TOX>GLIS2, TSPAN7>BCAS4, and PARD6G>NXN) was predictive for
      sensitivity to saracatinib. In addition, increased activation of the Src pathway
      was associated with sensitivity to saracatinib. These results suggest that FISH,
      a K-TSP classifier, and activation of the Src pathway have potential in
      identifying CRC patients that would potentially benefit from treatment with
      saracatinib.

PMID- 20682713
TI  - Genomic profiling reveals alternative genetic pathways of meningioma malignant
      progression dependent on the underlying NF2 status.
AB  - PURPOSE: Meningiomas are the most common central nervous system tumors in the
      population of age 35 and older. WHO defines three grades predictive of the risk
      of recurrence. Clinical data supporting histologic malignant progression of
      meningiomas are sparse and underlying molecular mechanisms are not clearly
      depicted. EXPERIMENTAL DESIGN: We identified genetic alterations associated with
      histologic progression of 36 paired meningioma samples in 18 patients using 500K
      SNP genotyping arrays and NF2 gene sequencing. RESULTS: The most frequent
      chromosome alterations observed in progressing meningioma samples are early
      alterations (i.e., present both in lower- and higher-grade samples of a single
      patient). In our series, NF2 gene inactivation was an early and frequent event in
      progressing meningioma samples (73%). Chromosome alterations acquired during
      progression from grade I to grade II meningioma were not recurrent. Progression
      to grade III was characterized by recurrent genomic alterations, the most
      frequent being CDKN2A/CDKN2B locus loss on 9p. CONCLUSION: Meningiomas displayed
      different patterns of genetic alterations during progression according to their
      NF2 status: NF2-mutated meningiomas showed higher chromosome instability during
      progression than NF2-nonmutated meningiomas, which had very few imbalanced
      chromosome segments. This pattern of alterations could thus be used as markers in
      clinical practice to identify tumors prone to progress among grade I meningiomas.

PMID- 20682714
TI  - HER2 fragmentation and breast cancer stratification.
AB  - HER2 is a tyrosine kinase receptor whose overexpression in breast cancers
      correlates with poor prognosis. A subset of HER2-positive tumors also expresses a
      series of HER2 fragments, collectively known as p95HER2. These fragments are
      emerging as a valuable biomarker for this subset of patients, who have a
      particularly poor prognosis.

PMID- 20682715
TI  - What can CCR do for you?

PMID- 20682716
TI  - The enigma of 7q36 linked autosomal dominant limb girdle muscular dystrophy.
AB  - INTRODUCTION: Two families with autosomal dominant limb girdle muscular dystrophy
      (LGMD) have previously been linked to a locus on chromosome 7q36 10 years ago.
      The locus has been termed both LGMD1D and 1E, but because of lack of additional
      families to narrow down the linked region of interest, this disease has remained
      elusive. METHODS: A large Finnish family was clinically and genetically
      investigated. Laboratory parameters were determined, including creatine kinase
      (CK) value, neurographic and electromyography studies, cardiac and respiratory
      function examinations, muscle biopsies and muscle imaging by CT or MRI. RESULTS:
      Patients had onset of muscle weakness in the pelvic girdle between the fourth and
      sixth decades with an autosomal dominant pattern of inheritance. CK values were
      slightly elevated and electromyography was myopathic only. Muscle biopsies showed
      myopathic and/or dystrophic features with very minor rimmed vacuolation and
      protein aggregation findings. Molecular genetic analysis indicates linkage of the
      disease to the locus on chromosome 7q36 completely overlapping with the
      previously reported locus LGMD1D/E. DISCUSSION: Advancement towards the causative
      gene defect in the 7q36 linked disease needs new additional families to narrow
      the region of interest. The phenotype in the previously linked families has not
      been reported in full detail, which may be one reason for the shortage of
      additional families. A comprehensive clinical and morphological phenotype of
      chromosome 7q36 linked autosomal dominant LGMD with a restricted and updated 6.4
      Mb sized haplotype is reported here.

PMID- 20682717
TI  - A wide spectrum of clinical, neurophysiological and neuroradiological
      abnormalities in a family with a novel CACNA1A mutation.
AB  - BACKGROUND: Mutations in the calcium channel voltage dependent P/Q-type alpha-1A
      subunit (CACNA1A) can cause different neurological disorders which share a wide
      range of symptoms, including episodic ataxia type 2 (EA2), familial hemiplegic
      migraine (FHM1) and progressive spinocerebellar ataxia (SCA6). OBJECTIVE: To
      describe a three generations family in which a spectrum of different phenotypes,
      ranging from SCA6 (proband), to EA2 (proband's mother) to FHM1 (proband's mother
      and proband's aunt) was found. All of the family members carried a novel CACNA1A
      missense mutation. PATIENTS AND METHODS: A clinical, molecular, neuroradiological
      and neurophysiological study was carried out in all subjects. RESULTS: A single
      heterozygous base change in exon 9, c1213G-->A, leading to the amino acid
      substitution pAla405Thr was found to segregate within the family. Brain MRI
      showed cerebellar and cerebral atrophy signs in all but one mutation carriers.
      Neurophysiological findings (electroencephalography and evoked potentials)
      confirmed possible cerebral cortex and white matter involvement regardless of the
      clinical symptoms displayed. CONCLUSIONS: This novel CACNA1A mutation adds to the
      number of mutations associated with a heterogeneous clinical picture in family
      members. This mutation might affect the interaction between the intracellular
      loops and the beta subunit, leading to a relatively rapid cell death. In order to
      explain the wide phenotypic variability observed in this family, it is
      hypothesised that additional genetic and environmental (hormonal) factors play a
      role in the pathophysiology of the disease.

PMID- 20682718
TI  - Neurological picture. Pendular nystagmus showing involvement of the floccular
      lobes in an atypical case of Wernicke encephalopathy: MRI findings.

PMID- 20682720
TI  - Predictors and long-term outcome of seizures after bacterial brain abscess.
AB  - BACKGROUND: Seizures are one of the most important neurological complications of
      bacterial brain abscesses. A better understanding of the risk factors of seizures
      following bacterial brain abscesses is needed to predict those who will require
      treatment. METHODS: A total of 205 patients were enrolled in this 22-year
      retrospective study. Prognostic variables were analysed based on Cox's
      proportional hazards model after a minimum of 18 months of follow-up. RESULTS:
      Seizures occurred in 48 patients who had bacterial brain abscesses, including
      acute symptomatic seizures in 17% (35/205) and unprovoked seizures in 6.4%
      (13/205). Altogether, 27 patients had early seizures and 21 had late seizures.
      The overall mortality rate in the seizure patients was 23% (11/48) and seven
      patients progressed to epilepsy. CONCLUSION: Cox's proportional hazards model
      demonstrated that valvular heart diseases as the underlying diseases and the
      presence of a fronto-parietal distribution of bacterial brain abscess were
      independently predictive of seizures, and the presence of late seizures was
      predictive of developing epilepsy. Most first seizures occurred within 3 y after
      bacterial brain abscesses.

PMID- 20682719
TI  - Recurrent stroke after cervical artery dissection.
AB  - OBJECTIVE: Cervical artery dissection (CAD) accounts for 10-20% of all strokes in
      young adults, but no randomised controlled trial has investigated the best
      secondary prevention after ischaemic stroke or transient ischaemic attack (TIA).
      Because only small numbers of patient with CAD have been prospectively documented
      and followed up, the authors aimed to investigate the prognosis under various
      prevention regimens. METHODS: 30 German departments of neurology with acute
      stroke units prospectively documented 250 patients with acute ischaemic stroke or
      TIA due to CAD. A central follow-up (median 31 months) assessed recurrent stroke,
      recurrent CAD and death in 198 patients. RESULTS: CAD was found more often in the
      carotid arteries (52.0%) than in the vertebral arteries (46.8%). Thirteen
      patients (5.2%, CI 3.1% to 8.6%) suffered a recurrent stroke during the acute
      hospital stay. The rate of recurrent CAD during the first year was 1.7% (95% CI
      0.3% to 3.6%). The cumulative recurrent stroke rate during the first year was
      10.7% (95% CI 6.5% to 14.9%) and 14.0% (95% CI 8.9% to 19.1%) over 3 years. After
      discharge, the rate of recurrent stroke up to 6 months in patients treated with
      anticoagulants was 2.0% (95% CI 0.6% to 7.1%) and in those treated with
      antiplatelets 16.7% (95% CI 5.8% to 39.2%), which was statistically significant
      (HR 0.11; CI 0.02 to 0.69, p=0.02). CONCLUSIONS: This observational study
      confirms a high risk of early recurrent stroke following acute IS or TIA due to
      CAD. Whether anticoagulation provides any benefit over antiplatelets needs to be
      investigated in a randomised controlled trial.

PMID- 20682721
TI  - Neurological picture. Wolfram syndrome associated with leukoencephalopathy.

PMID- 20682722
TI  - Long-term effects of vestibular compensation on balance control and sensory
      organisation after unilateral deafferentation due to vestibular schwannoma
      surgery.
AB  - The time-course of central adaptive mechanisms after vestibular schwannoma
      surgical removal allows, 3 months after surgery (middle term), a satisfactory
      recovery of balance control. However, the long-term evolution of postural control
      beyond the end of usual medical follow-up remains unknown. This longitudinal
      prospective study aimed to assess the long-term effects of vestibular
      compensation on balance control and sensory organisation in patients operated on
      for vestibular schwannoma. Thirty-six patients with vestibular schwannoma
      underwent vestibular and sensory organisation tests, shortly before and 3 months,
      6 months and 1 year after surgery. Postural control performances improved 3
      months after surgery compared with before surgery; they continued to improve at 6
      and 12 months after surgery, especially in conditions highly soliciting
      vestibular information. In the long term, strategies based on sensorimotor and/or
      behavioural substitution seem to be reinforced and fine-tuned, particularly in
      complex postural situations, for which only vestibular information is reliable to
      control balance.

PMID- 20682723
TI  - Retraction. Craniopharyngiomas in the posterior fossa: a rare subgroup,
      diagnosis, management, and outcomes.

PMID- 20682724
TI  - Retraction. Psychiatric side effects during methysergide treatment.

PMID- 20682725
TI  - Meta-analysis of RCTs finds that increasing consumption of polyunsaturated fat as
      a replacement for saturated fat reduces the risk of coronary heart disease.

PMID- 20682726
TI  - Tamoxifen, raloxifene and tibolone decrease risk of invasive breast cancer in
      healthy women but increase risk of thromboembolism (tamoxifen, raloxifene),
      endometrial cancer (tamoxifen) or stroke (tibolone).

PMID- 20682729
TI  - Consider surgery for elderly patients.

PMID- 20682730
TI  - Chronic aftershocks of an earthquake on the well-being of children in Haiti:
      violence, psychosocial health and slavery.

PMID- 20682732
TI  - Marking the operative site: a lesson learned.

PMID- 20682731
TI  - Temporal trends in revascularization and outcomes after acute myocardial
      infarction among the very elderly.
AB  - BACKGROUND: Few data are available on time-related changes in use and outcomes of
      invasive procedures after acute myocardial infarction in very elderly patients.
      Our objective was to describe trends in revascularization procedures and outcomes
      in a provincial cohort of very elderly patients who had experienced acute
      myocardial infarction. METHODS: We used a database of hospital discharge
      summaries to identify all patients aged 80 years or older admitted for acute
      myocardial infarction in Quebec. We used the provincial database of physicians'
      services and medication claims to assess treatment and obtain data on survival.
      RESULTS: Between March 1996 and March 2007, 29 750 patients aged 80 years or
      older were admitted to hospital for acute myocardial infarction. During this
      period, use of percutaneous coronary interventions increased from 2.2% to 24.9%,
      and use of coronary artery bypass graft surgery increased from 0.8% to 3.1%.
      Evidence-based prescriptions of medication increased over time (p < 0.001). The
      prevalence of reported comorbidities was higher during the period of 2003-2006
      than during the 1996-1999 period. One-year mortality improved over time (46.5%
      for 1996-1999 v. 40.9% for 2003-2006, p < 0.001) but remained unchanged in the
      subgroup of patients who did not undergo revascularization. INTERPRETATION: The
      use of revascularization, especially percutaneous coronary interventions, in the
      very elderly after acute myocardial infarction has been growing at a rapid pace,
      while the prevalence of reported comorbidities has been increasing in this
      population. Revascularization procedures are no longer restricted to younger
      patients. In the context of an aging population, it is imperative to determine
      whether these changes in practice are cost-effective.

PMID- 20682734
TI  - Five things to know about...diabetic retinopathy.

PMID- 20682736
TI  - 'Hodge-podge' regulation of alternative medicine in Canada.

PMID- 20682735
TI  - Health Canada sidesteps commitment to new salt reduction strategy.

PMID- 20682737
TI  - No end in sight for adult hepatitis B vaccine shortage.

PMID- 20682738
TI  - In Nepal, a woman's reproductive system is her greatest vulnerability.

PMID- 20682739
TI  - HIV-related criminal cases based on fear, not science, say advocates.

PMID- 20682740
TI  - Functional recovery following musculoskeletal injury in hospital workers.
AB  - BACKGROUND: Hospital workers are at high risk of work-related musculoskeletal
      disorders (WRMSDs), but outcomes following such injuries have not been well
      studied longitudinally. AIMS: To ascertain functional recovery in hospital
      workers following incident WRMSDs and identify predictors of functional status.
      METHODS: Cases (incident WRMSD) and matched referents from two hospitals were
      studied at baseline and at 2 year follow-up for health status [SF-12 physical
      component summary (PCS)], lost workdays, self-rated work effectiveness and work
      status change (job change or work cessation). Predictors included WRMSD and
      baseline demographics, socio-economic status (SES), job-related strain and effort
      reward imbalance. Logistic regression analysis tested longitudinal predictors of
      adverse functional status. RESULTS: The WRMSD-associated risk of poor (lowest
      quartile) PCS was attenuated from a baseline odds ratio (OR) of 5.2 [95%
      confidence interval (CI) 3.5-7.5] to a follow-up OR of 1.5 (95% CI 1.0-2.3) and
      was reduced further in multivariate modelling (OR = 1.4; 95% CI 0.9-2.2). At
      follow-up, WRMSD status did not predict significantly increased likelihood of
      lost workdays, decreased effectiveness or work status change. In multivariate
      modelling, lowest quintile SES predicted poor PCS (OR = 2.0; 95% CI 1.0-4.0) and
      work status change (OR = 2.5; 95% CI 1.1-5.8). High combined baseline job
      strain/effort-reward imbalance predicted poor PCS (OR = 1.7; 95% CI 1.1-2.7) and
      reduced work effectiveness (OR = 2.6; 95% CI 1.6-4.2) at follow-up. CONCLUSIONS:
      Baseline functional deficits associated with incident WRMSDs were largely
      resolved by 2 year follow-up. Nonetheless, lower SES and higher combined job
      strain/effort-reward imbalance predicted adverse outcomes, controlling for
      WRMSDs.

PMID- 20682741
TI  - Management of blood and body fluid exposures in police service staff.
AB  - BACKGROUND: Police service staff are at risk of occupational exposure to blood
      and body fluids with the consequent risk of blood-borne virus (BBV) infection.
      AIMS: To examine the types of occupational exposure incidents experienced by
      Scottish police service staff and to evaluate the post-incident management
      provided by their occupational health (OH) services. METHODS: Data were collected
      on the circumstances and the post-incident management of each incident reported
      to OH over 12 months. An expert panel reviewed the post-incident management
      provided by OH. RESULTS: The panel considered that the majority of cases of
      occupational exposure incurred little or no risk of BBV transmission. In general,
      the expert panel assessed the post-incident management provided by OH units
      serving the police as adequate and appropriate. However, some concerns were
      raised in relation to a small number of incorrect risk assessments and an
      inconsistent approach to hepatitis C virus (HCV) follow-up blood testing.
      CONCLUSIONS: The study findings suggest that most Scottish police OH departments
      were providing adequate post-incident management. There is, however, a need for
      more clarity around BBV risk assessment terminology and development of a
      standardized HCV testing protocol.

PMID- 20682742
TI  - Vibration-white foot: a case report.
AB  - BACKGROUND: Hand-arm vibration syndrome (HAVS) refers to the neurological,
      vascular and musculoskeletal problems that may arise due to exposure to segmental
      vibration to the hands. An analogous syndrome may occur in the lower extremities
      of workers exposed to foot-transmitted vibration. AIMS: This report describes the
      case of a worker with a history of foot-transmitted vibration exposure presenting
      with cold intolerance in the feet and blanching in the toes. Case report A 54
      year-old miner presented with a chief complaint of blanching and pain in his
      toes. The worker had a history of foot-transmitted vibration exposure over his 18
      year career as a miner, primarily from the operation of vehicle-mounted bolting
      machines. Cold provocation digital plethysmography showed cold-induced
      vasospastic disease in the feet, but not in the hands. CONCLUSIONS: This case
      illustrates a condition descriptively termed 'vibration-white foot': a disease
      analogous to HAVS arising after segmental vibration exposure to the feet. Further
      research is required to increase awareness of, and direct preventive efforts for,
      this potentially debilitating condition.

PMID- 20682743
TI  - The Fulani are not from the Middle East.

PMID- 20682745
TI  - To fold or expand--a charged question.

PMID- 20682746
TI  - Distinct subclasses of medium spiny neurons differentially regulate striatal
      motor behaviors.
AB  - The direct and indirect pathways of the basal ganglia have been proposed to
      oppositely regulate locomotion and differentially contribute to pathological
      behaviors. Analysis of the distinct contributions of each pathway to behavior has
      been a challenge, however, due to the difficulty of selectively investigating the
      neurons comprising the two pathways using conventional techniques. Here we
      present two mouse models in which the function of striatonigral or
      striatopallidal neurons is selectively disrupted due to cell type-specific
      deletion of the striatal signaling protein dopamine- and cAMP-regulated
      phosphoprotein Mr 32kDa (DARPP-32). Using these mice, we found that the loss of
      DARPP-32 in striatonigral neurons decreased basal and cocaine-induced locomotion
      and abolished dyskinetic behaviors in response to the Parkinson's disease drug L
      DOPA. Conversely, the loss of DARPP-32 in striatopallidal neurons produced a
      robust increase in locomotor activity and a strongly reduced cataleptic response
      to the antipsychotic drug haloperidol. These findings provide insight into the
      selective contributions of the direct and indirect pathways to striatal motor
      behaviors.

PMID- 20682747
TI  - MTM1 mutation associated with X-linked myotubular myopathy in Labrador
      Retrievers.
AB  - Mutations in the MTM1 gene encoding myotubularin cause X-linked myotubular
      myopathy (XLMTM), a well-defined subtype of human centronuclear myopathy. Seven
      male Labrador Retrievers, age 14-26 wk, were clinically evaluated for generalized
      weakness and muscle atrophy. Muscle biopsies showed variability in fiber size,
      centrally placed nuclei resembling fetal myotubes, and subsarcolemmal ringed and
      central dense areas highlighted with mitochondrial specific reactions.
      Ultrastructural studies confirmed the centrally located nuclei, abnormal
      perinuclear structure, and mitochondrial accumulations. Wild-type triads were
      infrequent, with most exhibiting an abnormal orientation of T tubules. MTM1 gene
      sequencing revealed a unique exon 7 variant in all seven affected males, causing
      a nonconservative missense change, p.N155K, which haplotype data suggest derives
      from a recent founder in the local population. Analysis of a worldwide panel of
      237 unaffected Labrador Retrievers and 59 additional control dogs from 25 other
      breeds failed to identify this variant, supporting it as the pathogenic mutation.
      Myotubularin protein levels and localization were abnormal in muscles from
      affected dogs, and expression of GFP-MTM1 p.N155K in COS-1 cells showed that the
      mutant protein was sequestered in proteasomes, where it was presumably misfolded
      and prematurely degraded. These data demonstrate that XLMTM in Labrador
      Retrievers is a faithful genetic model of the human condition.

PMID- 20682748
TI  - T-type channels control the opioidergic descending analgesia at the low threshold
      spiking GABAergic neurons in the periaqueductal gray.
AB  - Endogenous opioids generate analgesic signals in the periaqueductal gray (PAG).
      However, because cell types in the PAG are difficult to identify, its neuronal
      mechanism has remained poorly understood. To address this issue, we characterized
      PAG neurons by their electrical properties using differentially labeled GABAergic
      and output neurons in the PAG. We found that GABAergic neurons were mostly fast
      spiking cells and could be further divided into two distinct classes: with or
      without low-threshold spikes (LTS) driven by T-type channels. In contrast, the
      PAG output neurons lacked LTS and showed heterogeneous firing patterns. To reveal
      the function of the LTS, we examined the mutant mice lacking the alpha1G T-type
      channels (alpha1G(-/-)). The mutant mice lacked LTS in the fast-spiking GABAergic
      neurons of the PAG and unexpectedly showed impaired opioid-dependent analgesia; a
      similar phenotype was reproduced in PAG-specific alpha1G-knockdown mice.
      Electrophysiological analyses revealed functional expression of mu-opioid
      receptors in the low threshold-spiking GABAergic neurons. These neurons in the
      mutant lacking LTS showed markedly enhanced discharge activities, which led to an
      augmented inhibition of output neurons. Furthermore, the impaired analgesia
      observed in alpha1G(-/-) mice was reversed by blocking local GABA(A) receptors.
      These results indicate that alpha1G T-type channels are critical for the
      opioidergic descending analgesia system in the PAG.

PMID- 20682749
TI  - Isolation and identification of phase 1 metabolites of curcumol in rats.
AB  - Curcumol is one of the major components of the essential oil of Curcuma wenyujin
      with the structure of a guaiane-type sesquiterpenoid hemiketal. It exhibits clear
      antitumor, antihepatic fibrosis, antioxidant, and antimicrobial activities. In
      this article, the metabolism of curcumol in rats was investigated by
      characterizing metabolites excreted into urine. Sixteen phase 1 metabolites of
      curcumol were isolated from the urine of rats after an oral dose of 40 mg/kg, and
      their structures were elucidated on the basis of spectroscopic data. The
      metabolites were characterized as 2alpha-hydroxycurcumol (M-1), (11alphaH)-3alpha
      hydroxy-9-en-8,13-epoxycurcumol (M-2), (11alphaH)-14-hydroxy-9-en-8,13
      epoxycurcumol (M-3), (11betaH)-14-hydroxy-9-en-8,12-epoxycurcumol (M-4),
      10alpha,14-dihydroxy-(1alphaH,7betaH)-guai-4-en-3,8-dione (M-5), 10beta,14
      dihydroxy-(1alphaH,7betaH)-guai-4-en-3,8-dione (M-6), 10beta-hydroxy
      (1alphaH,7betaH,11alphaH)-guai-8(13),8(14)-diepoxy-4-en-3-one (M-7), 10beta
      hydroxy-(1alphaH,7betaH,11betaH)-guai-8(12),8(14)-diepoxy-4-en-3-one (M-8),
      10alpha-hydroxy-(1alphaH,7betaH,11alphaH)-guai-8(13), 8(14)-diepoxy-4-en-3-one (M
      9), 10alpha-hydroxy-(1alphaH,7betaH,11betaH)-guai-8(12),8(14)-diepoxy-4-en-3-one
      (M-10), 10alpha,14,15-trihydroxy-(1alphaH,7betaH)-guai-4-en-3,8-dione (M-11),
      10beta-hydroxy-(1alphaH,7betaH)-guai-4-en-3,8-dioxo-13-oic acid (M-12),
      (1alphaH,7betaH)-guai-4,10(14)-dien-3, 8-dioxo-13-oic acid (M-13), 5beta,10beta
      dihydroxy-(1alphaH,7betaH,11alphaH)-guai-8(13),8(14)-diepoxide (M-14), 10beta,14
      dihydroxycurcumol (M-15), and 5beta,10beta,14-trihydroxy-(1alphaH,7betaH)-guai-8
      one (M-16). All were newly identified compounds, among which M-3 and M-4, M-5 and
      M-6, and M-7, M-8, M-9, and M-10 are three groups of epimers. On the basis of the
      metabolite profile, the possible metabolic pathways of curcumol in rats are
      proposed. This is the first study of the metabolites of guaiane-type
      sesquiterpene in animals.

PMID- 20682750
TI  - Helicobacter pylori CagA inhibits endocytosis of cytotoxin VacA in host cells.
AB  - Helicobacter pylori, a common pathogen that causes chronic gastritis and cancer,
      has evolved to establish persistent infections in the human stomach.
      Epidemiological evidence suggests that H. pylori with both highly active
      vacuolating cytotoxin A (VacA) and cytotoxin-associated gene A (CagA), the major
      virulence factors, has an advantage in adapting to the host environment. However,
      the mechanistic relationship between VacA and CagA remains obscure. Here, we
      report that CagA interferes with eukaryotic endocytosis, as revealed by genome
      wide screening in yeast. Moreover, CagA suppresses pinocytic endocytosis and the
      cytotoxicity of VacA in gastric epithelial cells without affecting clathrin
      dependent endocytosis. Our data suggest that H. pylori secretes VacA to attack
      distant host cells while injecting CagA into the gastric epithelial cells to
      which the bacteria are directly attached, thereby protecting these attached host
      cells from the cytotoxicity of VacA and creating a local ecological niche. This
      mechanism might allow H. pylori to balance damage to one population of host cells
      with the preservation of another, allowing for persistent infection.

PMID- 20682751
TI  - Neuroprotection resulting from insufficiency of RANBP2 is associated with the
      modulation of protein and lipid homeostasis of functionally diverse but linked
      pathways in response to oxidative stress.
AB  - Oxidative stress is a deleterious stressor associated with a plethora of disease
      and aging manifestations, including neurodegenerative disorders, yet very few
      factors and mechanisms promoting the neuroprotection of photoreceptor and other
      neurons against oxidative stress are known. Insufficiency of RAN-binding protein
      2 (RANBP2), a large, mosaic protein with pleiotropic functions, suppresses
      apoptosis of photoreceptor neurons upon aging and light-elicited oxidative
      stress, and promotes age-dependent tumorigenesis by mechanisms that are not well
      understood. Here we show that, by downregulating selective partners of RANBP2,
      such as RAN GTPase, UBC9 and ErbB-2 (HER2; Neu), and blunting the upregulation of
      a set of orphan nuclear receptors and the light-dependent accumulation of
      ubiquitylated substrates, light-elicited oxidative stress and Ranbp2
      haploinsufficiency have a selective effect on protein homeostasis in the retina.
      Among the nuclear orphan receptors affected by insufficiency of RANBP2, we
      identified an isoform of COUP-TFI (Nr2f1) as the only receptor stably co
      associating in vivo with RANBP2 and distinct isoforms of UBC9. Strikingly, most
      changes in proteostasis caused by insufficiency of RANBP2 in the retina are not
      observed in the supporting tissue, the retinal pigment epithelium (RPE). Instead,
      insufficiency of RANBP2 in the RPE prominently suppresses the light-dependent
      accumulation of lipophilic deposits, and it has divergent effects on the
      accumulation of free cholesterol and free fatty acids despite the genotype
      independent increase of light-elicited oxidative stress in this tissue. Thus, the
      data indicate that insufficiency of RANBP2 results in the cell-type-dependent
      downregulation of protein and lipid homeostasis, acting on functionally
      interconnected pathways in response to oxidative stress. These results provide a
      rationale for the neuroprotection from light damage of photosensory neurons by
      RANBP2 insufficiency and for the identification of novel therapeutic targets and
      approaches promoting neuroprotection.

PMID- 20682752
TI  - Fragile X syndrome and model organisms: identifying potential routes of
      therapeutic intervention.
AB  - Fragile X syndrome (FXS) is a cognitive disorder caused by silencing of the
      fragile X mental retardation 1 gene (FMR1). Since the discovery of the gene
      almost two decades ago, most scientific contributions have focused on identifying
      the molecular function of the fragile X mental retardation protein (FMRP) and
      understanding how absence of FMR1 gene expression gives rise to the disease
      phenotypes. The use of model organisms has allowed rapid progression in the FXS
      field and has given insight into the molecular basis of the disease. The mouse
      and fly FXS models have enabled studies to identify potential targets and
      pathways for pharmacological treatment. Here, we briefly review the two primary
      FXS model systems and describe how studies in these organisms have led us closer
      to therapeutic treatments for patients afflicted with FXS.

PMID- 20682754
TI  - Sexual orientation perception involves gendered facial cues.
AB  - Perceivers can accurately judge a face's sexual orientation, but the perceptual
      mechanisms mediating this remain obscure. The authors hypothesized that
      stereotypes casting gays and lesbians as gender "inverts," in cultural
      circulation for a century and a half, lead perceivers to use gendered facial cues
      to infer sexual orientation. Using computer-generated faces, Study 1 showed that
      as two facial dimensions (shape and texture) became more gender inverted, targets
      were more likely to be judged as gay or lesbian. Study 2 showed that real faces
      appearing more gender inverted were more likely to be judged as gay or lesbian.
      Furthermore, the stereotypic use of gendered cues influenced the accurate
      judgment of sexual orientation. Although using gendered cues increased the
      accuracy of sexual orientation judgments overall, Study 3 showed that judgments
      were reliably mistaken for targets that countered stereotypes. Together, the
      findings demonstrate that perceivers utilize gendered facial cues to glean
      another's sexual orientation, and this influences the accuracy or error of
      judgments.

PMID- 20682755
TI  - A pilot study of gene/gene and gene/environment interactions in Alzheimer
      disease.
AB  - BACKGROUND: Although some genes associated with increased risk of Alzheimer
      Disease (AD) have been identified, few data exist related to gene/gene and
      gene/environment risk of AD. The purpose of this pilot study was to explore
      gene/gene and gene/environment associations in AD and to obtain data for sample
      size estimates for larger, more definitive studies of AD. METHODS: The effect of
      gene/gene and gene/environment interaction related to late onset Alzheimer
      Disease (LOAD) was investigated in 153 subjects with LOAD and 302 gender matched
      controls enrolled in the Personalized Medicine Research Project, a population
      based bio-repository. Genetic risk factors examined included APOE, ACE, OLR1,and
      CYP46 genes, and environmental factors included smoking, total cholesterol, LDL,
      HDL, triglycerides, C-reactive protein, blood pressure, statin use, and body mass
      index. RESULTS: The mean age of the cases was 78.2 years and the mean age of the
      controls was 87.2 years. APOE4 was significantly associated with LOAD (OR=3.55,
      95%CL=1.70, 7.45). Cases were significantly more likely to have ever smoked
      cigarettes during their life (49.3% versus 38.4%, p=0.03). The highest recorded
      blood pressure and pulse pressure measurements were significantly higher in the
      controls than the cases (all P<0.005). Although not statistically significant in
      this pilot study, the relationship of the following factors was associated in
      opposite directions with LOAD based on the presence of an APOE4 allele: obesity
      at the age of 50, ACE, OLR1, and CYP46. CONCLUSIONS: These pilot data suggest
      that gene/gene and gene/environment interactions may be important in LOAD, with
      APOE, a known risk factor for LOAD, affecting the relationship of ACE and OLR1 to
      LOAD. Replication with a larger sample size and in other racial/ethnic groups is
      warranted and the allele and risk factor frequencies will assist in choosing an
      appropriate sample size for a definitive study.

PMID- 20682756
TI  - Metabolic syndrome: comparison of occurrence using three definitions in
      hypertensive patients.
AB  - OBJECTIVE: To compare the frequency of occurrence of metabolic syndrome using
      three international definitions and to study the distribution of cardiovascular
      risk factors among newly diagnosed hypertensive Nigerian subjects. DESIGN: Cross
      sectional study. SETTINGS: Cardiology unit of LAUTECH Teaching Hospital, Osogbo,
      Nigeria. PARTICIPANTS: One hundred forty newly diagnosed hypertensive Nigerian
      subjects, and 70 normotensive controls (age- and sex-matched) were included in
      this study. METHODS: Clinical history and relevant laboratory investigations were
      performed on all study participants. The definition of metabolic syndrome was
      based on three international definitions: World Health Organization (WHO),
      International Diabetes Federation (IDF), and National Cholesterol Education
      Program Adult Treatment Panel III (NCEP ATP III). Ethical approval was obtained
      for the study. Statistical analyses were performed using SPSS 16.0. RESULTS:
      There was no difference in age and gender distribution between the hypertensive
      subjects and controls. (55.14 +/- 10.83 years, females 53.6% vs. 54.67 +/- 10.89
      years, females 52.9% respectively, P>0.05). The frequency of occurrence of
      metabolic syndrome among hypertensives was 34.5% according to WHO, 35.0%
      according to NCEP ATP III, and 42.5% according to IDF criteria. Visceral obesity
      and reduced high-density lipoprotein (HDL) were the other common cardiovascular
      risk factors among newly diagnosed hypertensive subjects. Female hypertensives
      had a higher prevalence of visceral obesity and low HDL. CONCLUSION: Frequency of
      occurrence of metabolic syndrome was similar using the NCEP ATP III and WHO
      definitions. However, the IDF definition resulted in a higher frequency because
      of the lower cut-off for waist circumference used for identification of visceral
      obesity. Metabolic syndrome is present in a significant proportion of newly
      diagnosed hypertensive subjects. Therefore, appropriate screening and treatment
      are required.

PMID- 20682757
TI  - Frequency of cardiovascular risk factors and metabolic syndrome in patients with
      chronic kidney disease.
AB  - OBJECTIVE: Metabolic syndrome is a clustering of cardio-metabolic risk factors.
      Cardiovascular disease is the main cause of morbidity and mortality in end-stage
      renal disease. The aim of this study was to elucidate the frequency of
      traditional and novel cardiovascular and metabolic syndrome risk factors in
      patients with chronic kidney disease. Identification of these risk factors will
      allow for precautions to be taken earlier to prevent cardiovascular diseases and
      metabolic syndrome in chronic kidney disease patients. METHODS: A total of 214
      patients (91 females, 123 males, mean age 56.1 +/- 14.4 years) with chronic
      kidney disease who were followed in the Nephrology Department of Istanbul Goztepe
      Training and Research Hospital were included in the study. Anthropometric and
      biochemical measurements for cardiovascular risk factors and metabolic syndrome
      parameters were recorded. Glomerular filtration rates (GFR) were estimated using
      the Cockroft Gault formula. Metabolic syndrome was defined according to
      International Diabetes Federation criteria. RESULTS: Thirty-seven percent of
      patients with chronic renal failure were found to have three or more major
      cardiovascular risk factors. Seventy percent of patients were found to have
      metabolic syndrome. The mean numbers of major cardiovascular risk factors and
      metabolic syndrome parameters in patients with different GFR stages were: 1.8 +/-
      1.0, 2.6 +/- 1.2 (GFR <15 mL/min per 1.73 m(2), n = 102); 2.4 +/- 1.0, 3.0 +/-
      1.0 (GFR 15-29 mL/min per 1.73 m(2), n = 51 ); 2.5 +/- 1.1, 3.3 +/- 1.0 (GFR 30
      59 mL/min per 1.73 m(2), n = 39); 2.4 +/- 1.1, 3.5 +/- 0.7 (GFR 60-89 mL/min per
      1.73 m(2), n = 22), respectively (P = .001). CONCLUSION: Although the frequency
      of cardiovascular risk factors and metabolic syndrome were high in patients with
      chronic kidney disease, they were negatively correlated with the stage of renal
      failure.

PMID- 20682758
TI  - Body mass index measurement and obesity prevalence in ten U.S. health plans.
AB  - OBJECTIVE: The objective of this study was to examine the frequency of body mass
      index (BMI) measurement before the implementation of two new Healthcare
      Effectiveness Data and Information Set (HEDIS) performance measures for obesity
      that require U.S. health plans to annually report the frequency of BMI and BMI
      percentile measurement among all adults and children who had at least one
      outpatient visit during the past two years. DESIGN: Cross-sectional study.
      SETTING: A consortium of ten U.S. health plans and care delivery systems from the
      Health Maintenance Organization Research Network, which together provide care to
      more than 6.5 million adults and children. PARTICIPANTS: Children and adults, age
      2 years and older, who were continuously enrolled in one of ten U.S. health plans
      for at least one full year from 2005 to 2006. METHODS: We extracted available
      anthropometric data for 3.7 million adults and 1.2 million children with at least
      one visit captured from ten electronic medical record databases from 2005 to
      2006. RESULTS: We found that the availability of BMI measurements for adults
      ranged widely across health plans from 28% to 88%, and availability of BMI
      percentiles for children ranged from 21% to 81%. Among adults and children with
      BMI measures in these ten health plans, the overall prevalence of overweight and
      obesity were very similar to those reported in the 2005 to 2006 U.S. national
      surveys that used measured heights and weights. CONCLUSION: The newly approved
      HEDIS performance measures likely represent an important step in addressing the
      quality of obesity care in the United States. The current study demonstrates that
      these HEDIS measures are achievable, especially among health plans that have
      implemented electronic medical records. Future research should assess the
      relationship between BMI assessment, provider counseling and treatment practices,
      and long-term changes in obesity rates among different population groups.

PMID- 20682759
TI  - Advanced practice nurses facilitating clinical translational research.
AB  - BACKGROUND: In 2006, the Clinical and Translational Science Award (CTSA),
      initiated by the National Center for Research Resources, was launched, with the
      overall goal to improve human health through clinical translational research. The
      purpose of this study was to examine the association between the total visit
      length for standardized study visits requiring the services of either a physician
      colleague or a designated advanced practice nurse (APN) for a protocol conducted
      in a clinical research center (CRC) supported with CTSA funds. METHODS: Data
      collected for administrative purposes between June 2008 and September 2009 were
      used. This retrospective study compared the total visit length for the
      standardized study visits of a single study protocol requiring a gluteal fat
      biopsy procedure performed by either a physician colleague (an MD in this case)
      or a CRC-based APN employed by the CRC. RESULTS: During the observed time period,
      67 gluteal fat biopsy procedures were performed by one physician colleague, and
      33 procedures were performed by one CRC-based APN. The mean total visit length of
      standardized study visits for research subjects treated by the physician
      colleague was 192.9 +/- 65.8 minutes, whereas the mean total visit length of
      standardized study visits for research subjects treated by the APN was 154.8 +/-
      40.9 minutes (P = .003). Generalized least squares random effects regression
      model further evaluated the association between provider and visit length while
      controlling for age, gender, percent body fat and physical activity. The type of
      provider (P < .001) and gender (P < .05) were associated with length of visit.
      CONCLUSIONS: The introduction of a CRC-based APN to perform advanced procedures
      demonstrates an efficient use of resources to meet the advanced clinical needs of
      specific research protocols. In this retrospective study, the ready availability
      of an APN (employed by the CRC) to perform gluteal fat biopsies during
      standardized study visits led to a decrease in total visit length, and thus a
      more rapid "turnover" of clinical research space compared to the use of a
      physician colleague. To best meet the needs of clinical researchers, CRCs should
      consider the employment of other clinicians to complement the research
      facilitation services provided by registered nurses. The addition of an APN to
      the CRC research facilitation team is novel and lends itself to the spirit of the
      clinical translational research initiative; additional studies evaluating the
      contribution of other licensed practitioners to improve research facilitation
      efficiency are needed.

PMID- 20682760
TI  - Impact of atrial fibrillation on outcome of patients with idiopathic dilated
      cardiomyopathy: data from the Heart Muscle Disease Registry of Trieste.
AB  - OBJECTIVE: There is a paucity and inconsistency of data regarding the natural
      history of patients affected by idiopathic dilated cardiomyopathy (IDCM) and
      atrial fibrillation (AF). We examined the prognostic implications of AF in a
      subset of patients with IDCM. METHODS: We analyzed the data of 539 patients with
      IDCM enrolled in the Heart Muscle Disease Registry of Trieste. RESULTS: At
      baseline, 52 (9.6%) of 539 patients had AF. There was no difference in survival
      of patients with either AF or sinus rhythm at enrollment (P = .28). During long
      term follow-up (90 +/- 58 months), AF was detected on ECG/ECG-Holter monitoring
      in 28 (5.7%) of 487 patients in sinus rhythm at baseline. Predictors of new onset
      of AF at multivariate analysis were a more dilated left atrium (OR 1.35, 95% CI
      1.06-1.72; P = .01) and a lower left ventricle ejection fraction (for 10%
      decrease, OR 2.41, 95% CI 1.24-4.69, P = .016). Patients developing AF had higher
      mortality/heart transplantation rate compared to patients who maintained sinus
      rhythm during follow-up (P < .001). At multivariate analysis, new onset AF (HR
      3.67, 95% CI 2.07-6.5; P < .001) in the first three years after diagnosis, but
      not baseline AF, was found to be independently associated with a worse outcome.
      CONCLUSIONS: Atrial fibrillation is relatively frequent in patients with IDCM.
      The early development of AF during follow-up, but not its presence at baseline,
      is associated with poor survival.

PMID- 20682761
TI  - Sequential multiplex analyte capturing for phosphoprotein profiling.
AB  - Microarray-based sandwich immunoassays can simultaneously detect dozens of
      proteins. However, their use in quantifying large numbers of proteins is hampered
      by cross-reactivity and incompatibilities caused by the immunoassays themselves.
      Sequential multiplex analyte capturing addresses these problems by repeatedly
      probing the same sample with different sets of antibody-coated, magnetic
      suspension bead arrays. As a miniaturized immunoassay format, suspension bead
      array-based assays fulfill the criteria of the ambient analyte theory, and our
      experiments reveal that the analyte concentrations are not significantly changed.
      The value of sequential multiplex analyte capturing was demonstrated by probing
      tumor cell line lysates for the abundance of seven different receptor tyrosine
      kinases and their degree of phosphorylation and by measuring the complex
      phosphorylation pattern of the epidermal growth factor receptor in the same
      sample from the same cavity.

PMID- 20682763
TI  - Probing the mechanism of cellulosome attachment to the Clostridium thermocellum
      cell surface: computer simulation of the Type II cohesin-dockerin complex and its
      variants.
AB  - The recalcitrance of lignocellulosic biomass to hydrolysis is the bottleneck in
      cellulosic ethanol production. Efficient degradation of biomass by the anaerobic
      bacterium Clostridium thermocellum is carried out by the multicomponent
      cellulosome complex. The bacterial cell-surface attachment of the cellulosome is
      mediated by high-affinity protein-protein interactions between the Type II
      cohesin domain borne by the cell envelope protein and the Type II dockerin
      domain, together with neighboring X-module present at the C-terminus of the
      scaffolding protein (Type II coh-Xdoc). Here, the Type II coh-Xdoc interaction is
      probed using molecular dynamics simulations, free-energy calculations and
      essential dynamics analyses on both the wild type and various mutants of the C.
      thermocellum Type II coh-Xdoc in aqueous solution. The simulations identify the
      hot spots, i.e. the amino acid residues that may lead to a dramatic decrease in
      binding affinity upon mutation and also probe the effects of mutations on the
      mode of binding. The results suggest that bulky and hydrophobic residues at the
      protein interface, which make specific contacts with their counterparts, may play
      essential roles in retaining a rigid cohesin-dockerin interface. Moreover,
      dynamical cross-correlation analysis indicates that the X-module has a dramatic
      effect on the cohesin-dockerin interaction and is required for the dynamical
      integrity of the interface.

PMID- 20682762
TI  - Toward next generation plasma profiling via heat-induced epitope retrieval and
      array-based assays.
AB  - There is a need for high throughput methods for screening patient samples in the
      quest for potential biomarkers for diagnostics and patient care. Here, we used a
      combination of undirected target selection, antibody suspension bead arrays, and
      heat-induced epitope retrieval to allow for protein profiling of human plasma in
      a novel and systematic manner. Several antibodies were found to reveal altered
      protein profiles upon epitope retrieval at elevated temperatures with limits of
      detection improving into lower ng/ml ranges. In a study based on prostate cancer
      patients, several proteins with differential profiles were discovered and
      subsequently validated in an independent cohort. For one of the potential
      biomarkers, the human carnosine dipeptidase 1 protein (CNDP1), the differences
      were determined to be related to the glycosylation status of the targeted
      protein. The study shows a path of pursuit for large scale screening of biobank
      repositories in a flexible and proteome-wide fashion by utilizing heat-induced
      epitope retrieval and using an antibody suspension bead array format.

PMID- 20682764
TI  - Phage-displayed peptides selected for binding to Campylobacter jejuni are
      antimicrobial.
AB  - In developed countries, Campylobacter jejuni is a leading cause of zoonotic
      bacterial gastroenteritis in humans with chicken meat implicated as a source of
      infection. Campylobacter jejuni colonises the lower gastrointestinal tract of
      poultry and during processing is spread from the gastrointestinal tract onto the
      surface of dressed carcasses. Controlling or eliminating C.jejuni on-farm is
      considered to be one of the best strategies for reducing human infection.
      Molecules on the cell surface of C.jejuni interact with the host to facilitate
      its colonisation and persistence in the gastrointestinal tract of poultry. We
      used a subtractive phage-display protocol to affinity select for peptides binding
      to the cell surface of a poultry isolate of C.jejuni with the aim of finding
      peptides that could be used to control this microorganism in chickens. In total,
      27 phage peptides, representing 11 unique clones, were found to inhibit the
      growth of C.jejuni by up to 99.9% in vitro. One clone was bactericidal, reducing
      the viability of C.jejuni by 87% in vitro. The phage peptides were highly
      specific. They completely inhibited the growth of two of the four poultry
      isolates of C.jejuni tested with no activity detected towards other Gram-negative
      and Gram-positive bacteria.

PMID- 20682765
TI  - Correctional officers' perceptions of a solution-focused training program:
      potential implications for working with offenders.
AB  - The purpose of this exploratory study was to explore correctional officers'
      perceptions and experiences during a solution-focused training program and to
      initiate development of a modified pattern for correctional officers to use in
      jails. The study uses grounded theory procedures combined with a follow-up
      survey. The findings identified six emergent themes: obstacles to doing
      counseling work in prisons, offenders' amenability to change, correctional
      officers' self-image, advantages of a solution-focused approach (SFA), potential
      advantages of applying SFA to offenders, and the need for the consolidation of
      learning and transformation. Participants perceived the use of solution-focused
      techniques as appropriate, important, functional, and of only moderate difficulty
      in interacting with offenders. Finally, a modified pattern was developed for
      officers to use when working with offenders in jails. Suggestions and
      recommendations are made for correctional interventions and future studies.

PMID- 20682766
TI  - Post-translational maturation of dystroglycan is necessary for pikachurin binding
      and ribbon synaptic localization.
AB  - Pikachurin, the most recently identified ligand of dystroglycan, plays a crucial
      role in the formation of the photoreceptor ribbon synapse. It is known that
      glycosylation of dystroglycan is necessary for its ligand binding activity, and
      hypoglycosylation is associated with a group of muscular dystrophies that often
      involve eye abnormalities. Because little is known about the interaction between
      pikachurin and dystroglycan and its impact on molecular pathogenesis, here we
      characterize the interaction using deletion constructs and mouse models of
      muscular dystrophies with glycosylation defects (Large(myd) and POMGnT1-deficient
      mice). Pikachurin-dystroglycan binding is calcium-dependent and relatively less
      sensitive to inhibition by heparin and high NaCl concentration, as compared with
      other dystroglycan ligand proteins. Using deletion constructs of the laminin
      globular domains in the pikachurin C terminus, we show that a certain steric
      structure formed by the second and the third laminin globular domains is
      necessary for the pikachurin-dystroglycan interaction. Binding assays using
      dystroglycan deletion constructs and tissue samples from Large-deficient
      (Large(myd)) mice show that Large-dependent modification of dystroglycan is
      necessary for pikachurin binding. In addition, the ability of pikachurin to bind
      to dystroglycan prepared from POMGnT1-deficient mice is severely reduced,
      suggesting that modification of the GlcNAc-beta1,2-branch on O-mannose is also
      necessary for the interaction. Immunofluorescence analysis reveals a disruption
      of pikachurin localization in the photoreceptor ribbon synapse of these model
      animals. Together, our data demonstrate that post-translational modification on O
      mannose, which is mediated by Large and POMGnT1, is essential for pikachurin
      binding and proper localization, and suggest that their disruption underlies the
      molecular pathogenesis of eye abnormalities in a group of muscular dystrophies.

PMID- 20682767
TI  - An atypical E3 ligase zinc finger protein 91 stabilizes and activates NF-kappaB
      inducing kinase via Lys63-linked ubiquitination.
AB  - The NF-kappaB transcription factors control many physiological processes,
      including inflammation, immunity, and apoptosis. Its activity contributes to the
      development of various cell malignancies. NF-kappaB-inducing kinase (NIK) plays a
      pivotal role in NF-kappaB activation. However, the molecular mechanism to
      stabilize and activate NIK remains elusive, although it is known that cIAP1/2
      (cellular inhibitor of apoptosis 1 and 2) ubiquitinate NIK for degradation. Here,
      we report a novel NF-kappaB-related zinc finger protein 91 (ZFP91) that
      stabilizes and activates NIK in a ubiquitination-dependent manner. We show that
      ZFP91 interacts with and promotes the Lys(63)-linked ubiquitination of NIK and
      subsequent processing of p100 to p52. The results of in vitro biochemical assays
      indicate that ZFP91 functions as an E3 ligase directly to NIK. Remarkably, the
      ubiquitination of NIK coincides with its Thr(559) phosphorylation. Furthermore,
      knockdown of ZFP91 expression by RNA interference inhibits the CD40 ligation
      induced activation of NIK and p100 processing as well as the expression of
      noncanonical NF-kappaB target genes. These data clearly indicate that ZFP91 is an
      important regulator of the noncanonical NF-kappaB pathway.

PMID- 20682768
TI  - Phosphorylation of CLK2 at serine 34 and threonine 127 by AKT controls cell
      survival after ionizing radiation.
AB  - AKT phosphorylates components of the intrinsic cell survival machinery and
      promotes survival to various stimuli. In the present study, we identified CDC
      like kinase 2 (CLK2) as a new substrate of AKT activation and elucidated its role
      in cell survival to ionizing radiation. AKT directly binds to and phosphorylates
      CLK2 on serine 34 and threonine 127, in vitro and in vivo. CLK2 phosphorylation
      was detected in HeLa cells overexpressing active AKT. In addition, we
      demonstrated that ionizing radiation induces CLK2 phosphorylation via AKT
      activation. In contrast, the suppression of endogenous AKT expression by siRNA
      inhibited CLK2 phosphorylation in response to 2 gray of gamma-ray or insulin.
      Furthermore, we examined the effect of CLK2 on the survival of irradiated CCD
      18Lu cells overexpressing Myc-CLK2. CLK2 overexpression significantly increased
      cell growth and inhibited cell death induced by 2 gray. The role of CLK2 in cell
      survival to ionizing radiation was dependent on the phosphorylation of serine 34
      and threonine 127. Our results suggest that AKT activation controls cell survival
      to ionizing radiation by phosphorylating CLK2, revealing an important regulatory
      mechanism required for promoting cell survival.

PMID- 20682769
TI  - Identification of a pentatricopeptide repeat protein implicated in splicing of
      intron 1 of mitochondrial nad7 transcripts.
AB  - Splicing of plant organellar transcripts is facilitated by members of a large
      protein family, the pentatricopeptide repeat proteins. We have identified a
      pentatricopeptide repeat protein in a genetic screen for mutants resistant to
      inhibition of root growth by buthionine sulfoximine (BSO), an inhibitor of
      glutathione synthesis and consequently named BIR6 (BSO-insensitive roots 6). BIR6
      is involved in splicing of intron 1 of the mitochondrial nad7 transcript. Loss-of
      function mutations in BIR6 result in a strongly reduced accumulation of fully
      processed nad7 transcript. This affects assembly of Complex I and results in
      moderate growth retardation. In agreement with disruption of Complex I function,
      the genes encoding alternative NADH oxidizing enzymes are induced in the mutant,
      and the mutant plants are less sensitive to mannitol and salt stress. Mutation in
      the BIR6 gene allowed normal root growth in presence of BSO and strongly
      attenuated depletion of glutathione content at these conditions. The same
      phenotype was observed with other mutants affected in function of Complex I, thus
      reinforcing the importance of Complex I function for cellular redox homeostasis.

PMID- 20682770
TI  - Identification of the matriptase second CUB domain as the secondary site for
      interaction with hepatocyte growth factor activator inhibitor type-1.
AB  - Matriptase is a type II transmembrane serine protease comprising 855 amino acid
      residues. The extracellular region of matriptase comprises a noncatalytic stem
      domain (containing two tandem repeats of complement proteases C1r/C1s-urchin
      embryonic growth factor-bone morphogenetic protein (CUB) domain) and a catalytic
      serine protease domain. The stem domain of matriptase contains site(s) for
      facilitating the interaction of this protease with the endogenous inhibitor,
      hepatocyte growth factor activator inhibitor type-1 (HAI-1). The present study
      aimed to identify these site(s). Analyses using a secreted variant of recombinant
      matriptase comprising the entire extracellular domain (MAT), its truncated
      variants, and a recombinant HAI-1 variant with an entire extracellular domain
      (HAI-1-58K) revealed that the second CUB domain (CUB domain II, Cys(340)
      Pro(452)) likely contains the site(s) of interest. We also found that MAT
      undergoes cleavage between Lys(379) and Val(380) within CUB domain II and that
      the C-terminal residues after Val(380) are responsible for facilitating the
      interaction with HAI-1-58K. A synthetic peptide corresponding to Val(380)
      Asp(390) markedly increased the matriptase-inhibiting activity of HAI-1-58K,
      whereas the peptides corresponding to Val(380)-Val(389) and Phe(382)-Asp(390) had
      no effect. HAI-1-58K precipitated with immobilized streptavidin resins to which a
      synthetic peptide Val(380)-Pro(392) with a biotinylated lysine residue at its C
      terminus was bound, suggesting direct interaction between CUB domain II and HAI
      1. These results led to the identification of the matriptase CUB domain II, which
      facilitates the primary inhibitory interaction between this protease and HAI-1.

PMID- 20682771
TI  - The C terminus of mouse monocyte chemoattractant protein 1 (MCP1) mediates MCP1
      dimerization while blocking its chemotactic potency.
AB  - The extracellular protease plasmin cleaves mouse MCP1 (monocyte chemoattractant
      protein 1) at lysine 104, releasing a 50-amino acid C-terminal domain. The
      cleavage event increases the chemotactic activity of MCP1 and, by doing so,
      promotes the progression of excitotoxic injury in the central nervous system in
      pathological settings. The mechanism through which the cleavage event enhances
      MCP1-mediated chemoattraction is unknown; to investigate it, we use wild-type and
      mutant forms of recombinant MCP1. Full-length MCP1 (FL-MCP1) is secreted by cells
      as a dimer or multimer. We show that a mutant truncated at the C terminus,
      K104Stop-MCP1, does not dimerize, revealing that the C terminus mediates the
      interaction. MCP1 interacts with the monocyte/microglia receptor CCR2. The
      interaction is critical to the function of MCP1 because CCR2(-/-) microglia do
      not undergo chemotaxis in response to MCP1 stimulation. We show that stimulation
      of microglia with FL-MCP1 or K104Stop-MCP1 triggers CCR2 internalization, whereas
      a mutant form unable to be cleaved at lysine 104 (K104A-MCP1) is relatively
      ineffective in this assay, suggesting that the C-terminal region interferes with
      the MCP1-CCR2 interaction. Moreover, FL-MCP1 and K104Stop-MCP1 stimulation leads
      to activation of Rac1, a small GTPase involved in cell migration. Conversely,
      MCP1-stimulated microglial migration is blocked by the Rac1 inhibitor, NSC23766,
      demonstrating the requirement for Rac1 effector pathways in this response. Taken
      together, we propose a model for MCP1 localization, activation, and function
      based on the initial presence and then removal of its C terminus, coupled with a
      requisite downstream signaling pathway from CCR2 stimulation to Rac1 activation.

PMID- 20682772
TI  - Protein-tyrosine phosphatase SHP2 contributes to GDNF neurotrophic activity
      through direct binding to phospho-Tyr687 in the RET receptor tyrosine kinase.
AB  - The signaling mechanisms by which neurotrophic receptors regulate neuronal
      survival and axonal growth are still incompletely understood. In the receptor
      tyrosine kinase RET, a receptor for GDNF (glial cell line-derived neurotrophic
      factor), the functions of the majority of tyrosine residues that become
      phosphorylated are still unknown. Here we have identified the protein-tyrosine
      phosphatase SHP2 as a novel direct interactor of RET and the first effector known
      to bind to phosphorylated Tyr(687) in the juxtamembrane region of the receptor.
      We show that SHP2 is recruited to RET upon ligand binding in a cooperative
      fashion, such that both interaction with Tyr(687) and association with components
      of the Tyr(1062) signaling complex are required for stable recruitment of SHP2 to
      the receptor. SHP2 recruitment contributes to the ability of RET to activate the
      PI3K/AKT pathway and promote survival and neurite outgrowth in primary neurons.
      Furthermore, we find that activation of protein kinase A (PKA) by forskolin
      reduces the recruitment of SHP2 to RET and negatively affects ligand-mediated
      neurite outgrowth. In agreement with this, mutation of Ser(696), a known PKA
      phosphorylation site in RET, enhances SHP2 binding to the receptor and eliminates
      the effect of forskolin on ligand-induced outgrowth. Together, these findings
      establish SHP2 as a novel positive regulator of the neurotrophic activities of
      RET and reveal Tyr(687) as a critical platform for integration of RET and PKA
      signals. We anticipate that several other phosphotyrosines of unknown function in
      neuronal receptor tyrosine kinases will also support similar regulatory
      functions.

PMID- 20682773
TI  - Prolyl isomerase Pin1 regulates transcription factor LSF (TFCP2) by facilitating
      dephosphorylation at two serine-proline motifs.
AB  - Transcription factor LSF is essential for cell cycle progression, being required
      for activating expression of the thymidylate synthase (Tyms) gene at the G1/S
      transition. We previously established that phosphorylation of LSF in early G1 at
      Ser-291 and Ser-309 inhibits its transcriptional activity and that
      dephosphorylation later in G1 is required for its reactivation. Here we reveal
      the role of prolyl cis-trans isomerase Pin1 in activating LSF, by facilitating
      dephosphorylation at both Ser-291 and Ser-309. We demonstrate that Pin1 binds LSF
      both in vitro and in vivo. Using coimmunoprecipitation assays, we identify three
      SP/TP motifs in LSF (at residues Ser-291, Ser-309, and Thr-329) that are required
      and sufficient for association with Pin1. Co-expression of Pin1 enhances LSF
      transactivation potential in reporter assays. The Pin1-dependent enhancement of
      LSF activity requires residue Thr-329 in LSF, requires both the WW and PPiase
      domains of Pin1, and correlates with hypophosphorylation of LSF at Ser-291 and
      Ser-309. These findings support a model in which the binding of Pin1 at the Thr
      329-Pro-330 motif in LSF permits isomerization by Pin1 of the peptide bonds at
      the nearby phosphorylated SP motifs (Ser-291 and Ser-309) to the trans
      configuration, thereby facilitating their dephosphorylation.

PMID- 20682774
TI  - Partial agonist and antagonist activities of a mutant scorpion beta-toxin on
      sodium channels.
AB  - Scorpion beta-toxin 4 from Centruroides suffusus suffusus (Css4) enhances the
      activation of voltage-gated sodium channels through a voltage sensor trapping
      mechanism by binding the activated state of the voltage sensor in domain II and
      stabilizing it in its activated conformation. Here we describe the antagonist and
      partial agonist properties of a mutant derivative of this toxin. Substitution of
      seven different amino acid residues for Glu(15) in Css4 yielded toxin derivatives
      with both increased and decreased affinities for binding to neurotoxin receptor
      site 4 on sodium channels. Css4(E15R) is unique among this set of mutants in that
      it retained nearly normal binding affinity but lost its functional activity for
      modification of sodium channel gating in our standard electrophysiological assay
      for voltage sensor trapping. More detailed analysis of the functional effects of
      Css4(E15R) revealed weak voltage sensor trapping activity, which was very rapidly
      reversed upon repolarization and therefore was not observed in our standard assay
      of toxin effects. This partial agonist activity of Css4(E15R) is observed clearly
      in voltage sensor trapping assays with brief (5 ms) repolarization between the
      conditioning prepulse and the test pulse. The effects of Css4(E15R) are fit well
      by a three-step model of toxin action involving concentration-dependent toxin
      binding to its receptor site followed by depolarization-dependent activation of
      the voltage sensor and subsequent voltage sensor trapping. Because it is a
      partial agonist with much reduced efficacy for voltage sensor trapping,
      Css4(E15R) can antagonize the effects of wild-type Css4 on sodium channel
      activation and can prevent paralysis by Css4 when injected into mice. Our results
      define the first partial agonist and antagonist activities for scorpion toxins
      and open new avenues of research toward better understanding of the structure
      function relationships for toxin action on sodium channel voltage sensors and
      toward potential toxin-based therapeutics to prevent lethality from scorpion
      envenomation.

PMID- 20682775
TI  - Fluid flow-induced soluble vascular endothelial growth factor isoforms regulate
      actin adaptation in osteoblasts.
AB  - Although load-induced mechanical signals play a key role in bone formation and
      maintenance of bone mass and structure, the cellular mechanisms involved in the
      translation of these signals are still not well understood. Recent identification
      of a novel flow-induced mechanosignaling pathway involving VEGF in osteoblasts
      and the known VEGF regulation of actin reorganization in various cell types has
      led us to hypothesize that fluid shear stress-induced Vegf up-regulation
      underlies the actin cytoskeleton adaptation observed in osteoblasts during
      mechanotransduction. Our results show that MC3T3-E1 cells secrete significant
      VEGF in response to 5 h of pulsatile fluid shear stress (PFSS; 5 dynes/cm(2) at 1
      Hz), whereas expression of VEGF receptors (VEGFR-1, VEGFR-2, or NRP1) is
      unaffected. These receptors, in particular VEGFR-2, participate in PFSS-induced
      VEGF release. Exposure to flow-conditioned medium or exogenous VEGF significantly
      induces stress fiber formation in osteoblasts that is comparable with PFSS
      induced stress fiber formation, whereas VEGF knockdown abrogates this response to
      PFSS, thereby providing evidence that flow-induced VEGF release plays a role in
      actin polymerization. Using neutralizing antibodies against the receptors and
      VEGF isoforms, we found that soluble VEGFs, in particular VEGF(164), play a
      crucial role in transient stress fiber formation during osteoblast
      mechanotransduction, most likely through VEGFR-2 and NRP1. Based on these data we
      conclude that flow-induced VEGF release from osteoblasts regulates osteoblast
      actin adaptation during mechanotransduction and that VEGF paracrine signaling may
      provide potent cross-talk among bone cells and endothelial cells that is
      essential for fracture healing, bone remodeling, and osteogenesis.

PMID- 20682776
TI  - Polarization and migration of hematopoietic stem and progenitor cells rely on the
      RhoA/ROCK I pathway and an active reorganization of the microtubule network.
AB  - Understanding the physiological migration of hematopoietic progenitors is
      important, not only for basic stem cell research, but also in view of their
      therapeutic relevance. Here, we investigated the role of the Rho kinase pathway
      in the morphology and migration of hematopoietic progenitors using an ex vivo co
      culture consisting of human primary CD34(+) progenitors and mesenchymal stromal
      cells. The addition of the Rho kinase inhibitor Y-27632 led to the abolishment of
      the uropod and microvillar-like structures of hematopoietic progenitors,
      concomitant with a redistribution of proteins found therein (prominin-1 and
      ezrin). Y-27632-treated cells displayed a deficiency in migration. Time-lapse
      video microscopy revealed impairment of the rear pole retraction. Interestingly,
      the knockdown of ROCK I, but not ROCK II, using RNA interference (RNAi) was
      sufficient to cause the referred morphological and migrational changes.
      Unexpectedly, the addition of nocodazole to either Y-27632- or ROCK I RNAi
      treated cells could restore their polarized morphology and migration suggesting
      an active role for the microtubule network in tail retraction. Finally, we could
      demonstrate using RNAi that RhoA, the upstream regulator of ROCK, is involved in
      these processes. Collectively, our data provide new insights regarding the role
      of RhoA/ROCK I and the microtubules in the migration of stem cells.

PMID- 20682777
TI  - Growth hormone (GH)-dependent expression of a natural antisense transcript
      induces zinc finger E-box-binding homeobox 2 (ZEB2) in the glomerular podocyte: a
      novel action of gh with implications for the pathogenesis of diabetic
      nephropathy.
AB  - Growth hormone (GH) excess results in structural and functional changes in the
      kidney and is implicated as a causative factor in the development of diabetic
      nephropathy (DN). Glomerular podocytes are the major barrier to the filtration of
      serum proteins, and altered podocyte function and/or reduced podocyte number is a
      key event in the pathogenesis of DN. We have previously shown that podocytes are
      a target for GH action. To elucidate the molecular basis for the effects of GH on
      the podocyte, we conducted microarray and RT-quantitative PCR analyses of
      immortalized human podocytes and identified zinc finger E-box-binding homeobox 2
      (ZEB2) to be up-regulated in a GH dose- and time-dependent manner. We established
      that the GH-dependent increase in ZEB2 levels is associated with increased
      transcription of a ZEB2 natural antisense transcript required for efficient
      translation of the ZEB2 transcript. GH down-regulated expression of E- and P
      cadherins, targets of ZEB2, and inhibited E-cadherin promoter activity. Mutation
      of ZEB2 binding sites on the E-cadherin promoter abolished this effect of GH on
      the E-cadherin promoter. Whereas GH increased podocyte permeability to albumin in
      a paracellular albumin influx assay, shRNA-mediated knockdown of ZEB2 expression
      abrogated this effect. We conclude that GH increases expression of ZEB2 in part
      by increasing expression of a ZEB2 natural antisense transcript. GH-dependent
      increase in ZEB2 expression results in loss of P- and E-cadherins in podocytes
      and increased podocyte permeability to albumin. Decreased expression of P- and E
      cadherins is implicated in podocyte dysfunction and epithelial-mesenchymal
      transition observed in DN. We speculate that the actions of GH on ZEB2 and P- and
      E-cadherin expression play a role in the pathogenesis of microalbuminuria of DN.

PMID- 20682778
TI  - Direct binding of the EGF-like domain of neuregulin-1 to integrins
      ({alpha}v{beta}3 and {alpha}6{beta}4) is involved in neuregulin-1/ErbB signaling.
AB  - Integrin-growth factor receptor cross-talk plays a role in growth factor
      signaling, but the specifics are unclear. In a current model, integrins and
      growth factor receptors independently bind to their ligands (extracellular matrix
      and growth factors, respectively). We discovered that neuregulin-1 (NRG1), either
      as an isolated EGF-like domain or as a native multi-domain form, binds to
      integrins alphavbeta3 (with a K(D) of 1.36 * 10(-7) m) and alpha6beta4. Docking
      simulation predicted that three Lys residues at positions 180, 184, and 186 of
      the EGF-like domain are involved in integrin binding. Mutating these residues to
      Glu individually or in combination markedly suppressed integrin binding and ErbB3
      phosphorylation. Mutating all three Lys residues to Glu (the 3KE mutation) did
      not affect the ability of NRG1 to bind to ErbB3 but markedly reduced the ability
      of NRG1 to induce ErbB3 phosphorylation and AKT and Erk1/2 activation in MCF-7
      and T47D human breast cancer cells. This suggests that direct integrin binding to
      NRG1 is critical for NRG1/ErbB signaling. Notably, stimulation of cells with WT
      NRG1 induced co-precipitation of ErbB3 with alpha6beta4 and with alphavbeta3 to a
      much lower extent. This suggests that WT NRG1 induces integrin-NRG1-ErbB3 ternary
      complex formation. In contrast, the 3KE mutant was much less effective in
      inducing ternary complex formation than WT NRG1, suggesting that this process
      depends on the ability of NRG1 to bind to integrins. These results suggest that
      direct NRG1-integrin interaction mediates integrin-ErbB cross-talk and that
      alpha6beta4 plays a major role in NRG-ErbB signaling in these cancer cells.

PMID- 20682779
TI  - Association among amyloid plaque, lipid, and creatine in hippocampus of TgCRND8
      mouse model for Alzheimer disease.
AB  - Amyloid peptide (Abeta) aggregation in the brain is a characteristic feature of
      Alzheimer disease (AD). Previously, we reported the discovery of focally elevated
      creatine deposits in brain tissue from TgCRND8 mice, which express double mutant
      (K670N/M671L and V717F) amyloid protein precursor. In this study, frozen
      hippocampal tissue sections from 5-, 8-, 11-, 14-, and 17-month old TgCRND8 and
      littermate control mice were examined with Fourier transform infrared
      microspectroscopy to explore the distribution of lipid, creatine, and dense core
      plaque deposits. Lipid distribution throughout the hippocampus was similar in
      transgenic (Tg) and non-Tg littermates at all ages. Dense core plaques were
      always found to lie within a thin (30-50 MUm) lipid envelope, confirmed by
      imaging through serial sections. Creatine deposits were found in all TgCRND8
      mice; the extent of deposition increased with age. Minor creatine deposits
      appeared in the oldest littermate controls. Distribution in the serial sections
      showed moderate correlation between layers, slightly disturbed by the freeze/thaw
      process. Creatine deposits in Tg mice were not specifically co-localized with
      plaques or lipid halos. The dimension of the lipid envelope is comparable with
      that of the diffuse halo of nonaggregated amyloid, implying a dynamic association
      in vivo, postulated to have a significant role in the evolving neurotoxicity.

PMID- 20682780
TI  - The p38 SAPK is recruited to chromatin via its interaction with transcription
      factors.
AB  - In mammals, the stress-activated protein kinase (SAPK) p38 coordinates a rapid
      and complex transcriptional program to adapt to sudden changes in the
      extracellular environment. Although a number of genes have been reported to be
      under the control of p38, the basic mechanisms of transcriptional regulation by
      this SAPK remain uncharacterized. Here we show that in response to osmotic shock,
      anisomycin- or TNFalpha-activated p38 SAPK is recruited to stress-induced genes.
      The MAPKK MKK6 is also found at stress-responsive promoters. The recruitment of
      RNA polymerase II complex to the target promoters requires p38 activity.
      Moreover, when tethered to DNA as a LexA fusion protein, p38 activates
      transcription in a stress-regulated manner. Thus, p38 activity allows for
      recruitment of RNA polymerase and transcription initiation. p38 directly
      phosphorylates and interacts with the transcription factor Elk1. p38 activity is
      necessary for the recruitment of Elk1 to the c-Fos promoter, and knocking down
      Elk1 by siRNAs compromises both p38 recruitment to the c-Fos promoter and c-Fos
      transcriptional up-regulation upon osmostress. In addition, p38 recruitment to
      the osmoinducible gene Cox2 and the TNFalpha target gene IL8 is mediated by the
      transcription factors AP1 and NFkappaB, respectively. Therefore, anchoring of
      active SAPK to target genes is mediated by transcription factors. The presence of
      active p38 at open reading frames also suggests the involvement of the SAPK in
      elongation. Taken together, SAPK recruitment to target genes appears to be a
      broad mechanism to regulate transcription that has been preserved from yeast to
      mammals.

PMID- 20682781
TI  - ZRT/IRT-like protein 14 (ZIP14) promotes the cellular assimilation of iron from
      transferrin.
AB  - ZIP14 is a transmembrane metal ion transporter that is abundantly expressed in
      the liver, heart, and pancreas. Previous studies of HEK 293 cells and the
      hepatocyte cell lines AML12 and HepG2 established that ZIP14 mediates the uptake
      of non-transferrin-bound iron, a form of iron that appears in the plasma during
      pathologic iron overload. In this study we investigated the role of ZIP14 in the
      cellular assimilation of iron from transferrin, the circulating plasma protein
      that normally delivers iron to cells by receptor-mediated endocytosis. We also
      determined the subcellular localization of ZIP14 in HepG2 cells. We found that
      overexpression of ZIP14 in HEK 293T cells increased the assimilation of iron from
      transferrin without increasing levels of transferrin receptor 1 or the uptake of
      transferrin. To allow for highly specific and sensitive detection of endogenous
      ZIP14 in HepG2 cells, we used a targeted knock-in approach to generate a cell
      line expressing a FLAG-tagged ZIP14 allele. Confocal microscopic analysis of
      these cells detected ZIP14 at the plasma membrane and in endosomes containing
      internalized transferrin. HepG2 cells in which endogenous ZIP14 was suppressed by
      siRNA assimilated 50% less iron from transferrin compared with controls. The
      uptake of transferrin, however, was unaffected. We also found that ZIP14 can
      mediate the transport of iron at pH 6.5, the pH at which iron dissociates from
      transferrin within the endosome. These results suggest that endosomal ZIP14
      participates in the cellular assimilation of iron from transferrin, thus
      identifying a potentially new role for ZIP14 in iron metabolism.

PMID- 20682782
TI  - The pseudo signal peptide of the corticotropin-releasing factor receptor type 2a
      decreases receptor expression and prevents Gi-mediated inhibition of adenylyl
      cyclase activity.
AB  - The corticotropin-releasing factor receptor type 2a (CRF(2(a))R) belongs to the
      family of G protein-coupled receptors. The receptor possesses an N-terminal
      pseudo signal peptide that is unable to mediate targeting of the nascent chain to
      the endoplasmic reticulum membrane during early receptor biogenesis. The pseudo
      signal peptide remains uncleaved and consequently forms an additional hydrophobic
      receptor domain with unknown function that is unique within the large G protein
      coupled receptor protein family. Here, we have analyzed the functional
      significance of this domain in comparison with the conventional signal peptide of
      the homologous corticotropin-releasing factor receptor type 1 (CRF(1)R). We show
      that the presence of the pseudo signal peptide leads to a very low cell surface
      receptor expression of the CRF(2(a))R in comparison with the CRF(1)R. Moreover,
      whereas the presence of the pseudo signal peptide did not affect coupling to the
      G(s) protein, G(i)-mediated inhibition of adenylyl cyclase activity was
      abolished. The properties mediated by the pseudo signal peptide were entirely
      transferable to the CRF(1)R in signal peptide exchange experiments. Taken
      together, our results show that signal peptides do not only influence early
      protein biogenesis. In the case of the corticotropin-releasing factor receptor
      subtypes, the use of conventional and pseudo signal peptides have an unexpected
      influence on signal transduction.

PMID- 20682783
TI  - Characterization of O-phosphohydroxyproline in rat {alpha}-crystallin A.
AB  - Post-translational modifications have major importance for the structure and
      function of a multiplicity of proteins. Phosphorylation is a widespread
      phenomenon among eukaryotic proteins. Whereas O-phosphorylation on the side
      chains of serine, threonine, and tyrosine in proteins is well known and has been
      studied extensively, to our knowledge the endogenous phosphorylation of
      hydroxyproline has not previously been reported. In the present work, we provide
      evidence for the first time that O-phosphohydroxyproline (Hyp(P)) is a
      proteinogenic amino acid. To detect Hyp(P) in proteins we generated a Hyp(P)
      specific polyclonal antibody. We could identify Hyp(P) in various proteins by
      Western blot analysis, and we characterized the sequence position of Hyp(P) in
      the protein alpha-crystallin A by electrospray ionization-tandem mass
      spectrometry. Our experiments clearly demonstrate hydroxylation and subsequent
      phosphorylation of a proline residue in alpha-crystallin A in the eye as well as
      in heart tissue of rat.

PMID- 20682784
TI  - Flexible regions within I{kappa}B{alpha} create the ubiquitin-independent
      degradation signal.
AB  - Homeostatic regulation of NF-kappaB requires the continuous synthesis of
      IkappaBalpha and its rapid degradation by the proteasome through a ubiquitin
      independent pathway. We previously showed that the ubiquitin-independent
      degradation signal of unbound IkappaBalpha was located in the C-terminal PEST
      region, and we have now identified a single tyrosine, Tyr-289, and determined
      that the hydrophobic character of the tyrosine is important for the rapid
      turnover of IkappaBalpha. The sequence composition of the PEST peptide
      surrounding this Tyr-289 imposes a distinct polyproline II conformation.
      Enhancing the polyproline II helix formation correlates with slower degradation
      rates of unbound IkappaBalpha. We have further identified a degradation signal
      located within the 5th ankyrin repeat that is functional once the C terminus is
      removed. Both the C-terminal and 5th ankyrin repeat degradation signals have
      inherent flexibility and specific hydrophobic residue(s), which together
      constitute the ubiquitin-independent degradation signal for IkappaBalpha.

PMID- 20682785
TI  - Mechanism of E1-E2 interaction for the inhibition of Ubl adenylation.
AB  - Conjugates of ubiquitin or its homologues to other proteins occur by strictly
      ordered steps with ordered addition of substrates for each step. High
      concentrations of E2 were shown to inhibit the formation of E2~Ubl thioester and
      Ubl~target conjugates. We investigated the mechanism of such inhibitory effect of
      the SUMO E2 and whether the E2 has two binding sites on its E1, one for the
      inhibitory effect and one for productive SUMOylation. NMR methods in combination
      with mutagenesis and biochemical assays revealed that Ubc9 binds to two flexible
      domains of its free E1 simultaneously, suggesting extensive domain movements in
      the free E1. Further, interaction of free E1 and E2 inhibits SUMO adenylation,
      and the interfaces responsible for the inhibition were the same as those required
      for productive transfer of SUMO from E1 to E2. This study indicates a
      conformational flexibility-dependent mechanism to control the strictly ordered
      steps in Ubl modifications.

PMID- 20682786
TI  - Identification of novel inhibitors of 1-aminocyclopropane-1-carboxylic acid
      synthase by chemical screening in Arabidopsis thaliana.
AB  - Ethylene is a gaseous hormone important for adaptation and survival in plants. To
      further understand the signaling and regulatory network of ethylene, we used a
      phenotype-based screening strategy to identify chemical compounds interfering
      with the ethylene response in Arabidopsis thaliana. By screening a collection of
      10,000 structurally diverse small molecules, we identified compounds suppressing
      the constitutive triple response phenotype in the ethylene overproducer mutant
      eto1-4. The compounds reduced the expression of a reporter gene responsive to
      ethylene and the otherwise elevated level of ethylene in eto1-4. Structure and
      function analysis revealed that the compounds contained a quinazolinone backbone.
      Further studies with genetic mutants and transgenic plants involved in the
      ethylene pathway showed that the compounds inhibited ethylene biosynthesis at the
      step of converting S-adenosylmethionine to 1-aminocyclopropane-1-carboxylic acid
      (ACC) by ACC synthase. Biochemical studies with in vitro activity assay and
      enzyme kinetics analysis indicated that a representative compound was an
      uncompetitive inhibitor of ACC synthase. Finally, global gene expression
      profiling uncovered a significant number of genes that were co-regulated by the
      compounds and aminoethoxyvinylglycine, a potent inhibitor of ACC synthase. The
      use of chemical screening is feasible in identifying small molecules modulating
      the ethylene response in Arabidopsis seedlings. The discovery of such chemical
      compounds will be useful in ethylene research and can offer potentially useful
      agrochemicals for quality improvement in post-harvest agriculture.

PMID- 20682787
TI  - Intestinal cell calcium uptake and the targeted knockout of the 1,25D3-MARRS
      (membrane-associated, rapid response steroid-binding) receptor/PDIA3/Erp57.
AB  - We have crossed ERp57(flx/flx) mice with commercially available mice expressing
      villin-driven cre-recombinase. Lysates of intestinal epithelial cells were
      prepared from knock-out (KO) mice and littermates (LM) and used in Western blot
      analyses with Ab099 against the N terminus of the 1,25D(3)-MARRS (membrane
      associated, rapid response steroid-binding) receptor: LM mice exhibited one
      positive band, which was absent in preparations from KO mice. Saturation analyses
      of cell lysates with [(3)H]1,25D(3) revealed negligible binding in preparations
      from either female or male KOs. Lysates from female and male LM mice had similar
      affinities but different numbers of binding sites. Isolated enterocytes were
      tested for steroid-stimulated calcium uptake. Treatment of cells from female or
      male LM mice with 1,25D(3) elicited enhanced calcium uptake in females and males
      within 5 min. Intestinal cells from KO mice exhibited a severely blunted or
      completely absent response to hormone. Confocal microscopy of intestinal cells
      revealed the presence of cell surface vitamin D receptors. However, antibodies to
      the vitamin D receptor failed to block 1,25D(3)-stimulated calcium uptake. In
      chick enterocytes we have found that the PKA pathway mediates calcium uptake. The
      time course for activation of PKA in mouse enterocytes paralleled that for
      enhanced calcium uptake and for LM females reached 250% of controls within 5 min,
      and 150% of controls in cells prepared from LM males. Enterocytes from female or
      male KO mice failed to exhibit steroid hormone-stimulated PKA activity, but did
      respond to forskolin with enhanced calcium uptake. We conclude that the 1,25D(3)
      MARRS receptor is of central importance to steroid hormone-stimulated calcium
      uptake in mammalian intestinal cells.

PMID- 20682788
TI  - Root secretion of defense-related proteins is development-dependent and
      correlated with flowering time.
AB  - Proteins found in the root exudates are thought to play a role in the
      interactions between plants and soil organisms. To gain a better understanding of
      protein secretion by roots, we conducted a systematic proteomic analysis of the
      root exudates of Arabidopsis thaliana at different plant developmental stages. In
      total, we identified 111 proteins secreted by roots, the majority of which were
      exuded constitutively during all stages of development. However, defense-related
      proteins such as chitinases, glucanases, myrosinases, and others showed enhanced
      secretion during flowering. Defense-impaired mutants npr1-1 and NahG showed lower
      levels of secretion of defense proteins at flowering compared with the wild type.
      The flowering-defective mutants fca-1, stm-4, and co-1 showed almost undetectable
      levels of defense proteins in their root exudates at similar time points. In
      contrast, root secretions of defense-enhanced cpr5-2 mutants showed higher levels
      of defense proteins. The proteomics data were positively correlated with
      enzymatic activity assays for defense proteins and with in silico gene expression
      analysis of genes specifically expressed in roots of Arabidopsis. In conclusion,
      our results show a clear correlation between defense-related proteins secreted by
      roots and flowering time.

PMID- 20682789
TI  - p38 regulates expression of osteoblast-specific genes by phosphorylation of
      osterix.
AB  - Osterix, a zinc finger transcription factor, is specifically expressed in
      osteoblasts and osteocytes of all developing bones. Because no bone formation
      occurs in Osx-null mice, Osterix is thought to be an essential regulator of
      osteoblast differentiation. We report that, in several mesenchymal and
      osteoblastic cell types, BMP-2 induces an increase in expression of the two
      isoforms of Osterix arising from two alternative promoters. We identified a
      consensus Sp1 sequence (GGGCGG) as Osterix binding regions in the fibromodulin
      and the bone sialoprotein promoters in vitro and in vivo. Furthermore, we show
      that Osterix is a novel substrate for p38 MAPK in vitro and in vivo and that Ser
      73 and Ser-77 are the regulatory sites phosphorylated by p38. Our data also
      demonstrate that Osterix is able to increase recruitment of p300 and Brg1 to the
      promoters of its target genes fibromodulin and bone sialoprotein in vivo and that
      it directly associates with these cofactors through protein-protein interactions.
      Phosphorylation of Osterix at Ser-73/77 increased its ability to recruit p300 and
      SWI/SNF to either fibromodulin or bone sialoprotein promoters. We therefore
      propose that Osterix binds to Sp1 sequences on target gene promoters and that its
      phosphorylation by p38 enhances recruitment of coactivators to form
      transcriptionally active complexes.

PMID- 20682790
TI  - Alternatively spliced caspase-6B isoform inhibits the activation of caspase-6A.
AB  - Caspase-6 (Casp6) is activated early in Alzheimer disease and involved in axonal
      degeneration, but the regulation of Casp6 activity has not been explored. Several
      alternatively spliced forms of caspases act as inhibitors of caspase activation.
      The CASP6 gene generates an alternatively spliced transcript known as CASP6beta
      in addition to the CASP6alpha that encodes pro-Casp6a. Here, we show that the
      CASP6beta transcript and the pro-Casp6b protein are present in many cell lines,
      in primary human neurons, and in human brains. Unlike most other alternatively
      spliced caspase transcripts, pro-Casp6b contains a catalytic site. However,
      purified pro-Casp6b did not have caspase activity, nor did it inhibit already
      activated Casp6a. Pro-Casp6b prevented the proteolytic activation of pro-Casp6a
      in vitro and in cells. Pro-Casp6b interacts directly with pro-Casp6a. This work
      shows that pro-Casp6b is an inhibitor of pro-Casp6a activation. These results
      imply that pro-Casp6b could negatively regulate pro-Casp6a activation in neurons
      and prevent Casp6a-mediated axonal degeneration.

PMID- 20682791
TI  - A protein interaction network for Ecm29 links the 26 S proteasome to molecular
      motors and endosomal components.
AB  - Ecm29 is a 200-kDa HEAT repeat protein that binds the 26 S proteasome. Genome
      wide two-hybrid screens and mass spectrometry have identified molecular motors,
      endosomal components, and ubiquitin-proteasome factors as Ecm29-interacting
      proteins. The C-terminal half of human Ecm29 binds myosins and kinesins; its N
      terminal region binds the endocytic proteins, Vps11, Rab11-FIP4, and rabaptin.
      Whereas full-length FLAG-Ecm29, its C-terminal half, and a small central fragment
      of Ecm29 remain bound to glycerol-gradient-separated 26 S proteasomes, the N
      terminal half of Ecm29 does not. Confocal microscopy showed that Ecm-26 S
      proteasomes are present on flotillin-positive endosomes, but they are virtually
      absent from caveolin- and clathrin-decorated endosomes. Expression of the small
      central fragment of Ecm29 markedly reduces proteasome association with flotillin
      positive endosomes. Identification of regions within Ecm29 capable of binding
      molecular motors, endosomal proteins, and the 26 S proteasome supports the
      hypothesis that Ecm29 serves as an adaptor for coupling 26 S proteasomes to
      specific cellular compartments.

PMID- 20682792
TI  - Review of outcomes of cardiac support groups after cardiac events.
AB  - Cardiac support groups may positively affect adjustment after cardiac events and
      quality of life (QoL). However, although participation in support groups is
      presumed to be beneficial, there were few studies regarding the potential
      benefit. The purpose of this review was to examine studies focused on the effects
      of cardiac support groups on health-related outcomes. Four studies met the
      inclusion criteria for review. Eight categories of support group outcomes were
      identified, including psychological outcomes, health behaviors, clinical health,
      health-related QoL, self-reported health conditions, social support, life
      situation, and knowledge. Most cardiac support group outcomes, though positive,
      were not statistically significantly different from those of control groups in
      studies reviewed. Psychosocial need of patients following cardiac events is
      indicated, including stress management and social support, and encouraging the
      establishment of realistic individual goals. More research is needed to establish
      cost-effective formats for support groups and to determine specific outcomes that
      can be achieved.

PMID- 20682793
TI  - CD73: a novel target for cancer immunotherapy.
AB  - The promise of cancer immunotherapy has not been translated into clinical
      successes, in large part because of tumor-associated immune suppression that
      blocks effective antitumor immunity. Recent findings show a tumor-induced
      immunosuppressive mechanism, whereby tumor-derived CD73 functions as an ecto
      enzyme to produce extracellular adenosine, which promotes tumor growth by
      limiting antitumor T-cell immunity via adenosine receptor signaling. Results with
      small molecule inhibitors, or monoclonal antibodies targeting CD73 in murine
      tumor models, suggest that targeted CD73 therapy is an important alternative and
      realistic approach to effective control of tumor growth. In particular, it helps
      T-cell-based therapy by enhancing the adaptive immune response machinery, which
      may increase the function of tumor-infiltrating T lymphocytes, and subsequently
      lead to improved survival in cancer patients.

PMID- 20682794
TI  - KRAB zinc finger protein ZNF382 is a proapoptotic tumor suppressor that represses
      multiple oncogenes and is commonly silenced in multiple carcinomas.
AB  - Zinc finger transcription factors are involved broadly in development and
      tumorigenesis. Here, we report that the little studied zinc finger transcription
      factor ZNF382 functions as a tumor suppressor in multiple carcinomas. Although
      broadly expressed in normal tissues, ZNF382 expression was attenuated in multiple
      carcinoma cell lines due to promoter CpG methylation. ZNF382 was also frequently
      methylated in multiple primary tumors (nasopharyngeal, esophageal, colon,
      gastric, and breast). Ectopic expression of ZNF382 in silenced tumor cells
      significantly inhibited their clonogenicity and proliferation and induced
      apoptosis. We further found that ZNF382 inhibited NF-kappaB and AP-1 signaling
      and downregulated the expression of multiple oncogenes including MYC, MITF,
      HMGA2, and CDK6, as well as the NF-kappaB upstream factors STAT3, STAT5B, ID1,
      and IKBKE, most likely through heterochromatin silencing. ZNF382 could suppress
      tumorigenesis through heterochromatin-mediated silencing, as ZNF382 was
      colocalized and interacted with heterochromatin protein HP1 and further changed
      the chromatin modifications of ZNF382 target oncogenes. Our data show that ZNF382
      is a functional tumor suppressor frequently methylated in multiple carcinomas.

PMID- 20682795
TI  - Epigenetic silencing of miR-137 is an early event in colorectal carcinogenesis.
AB  - Global downregulation of microRNAs (miRNA) is a common feature in colorectal
      cancer (CRC). Whereas CpG island hypermethylation constitutes a mechanism for
      miRNA silencing, this field largely remains unexplored. Herein, we describe the
      epigenetic regulation of miR-137 and its contribution to colorectal
      carcinogenesis. We determined the methylation status of miR-137 CpG island in a
      panel of six CRC cell lines and 409 colorectal tissues [21 normal colonic mucosa
      from healthy individuals (N-N), 160 primary CRC tissues and their corresponding
      normal mucosa (N-C), and 68 adenomas]. TaqMan reverse transcription-PCR and in
      situ hybridization were used to analyze miR-137 expression. In vitro functional
      analysis of miR-137 was performed. Gene targets of miR-137 were identified using
      a combination of bioinformatic and transcriptomic approaches. We experimentally
      validated the miRNA:mRNA interactions. Methylation of the miR-137 CpG island was
      a cancer-specific event and was frequently observed in CRC cell lines (100%),
      adenomas (82.3%), and CRC (81.4%), but not in N-C (14.4%; P < 0.0001 for CRC) and
      N-N (4.7%; P < 0.0001 for CRC). Expression of miR-137 was restricted to the
      colonocytes in normal mucosa and inversely correlated with the level of
      methylation. Transfection of miR-137 precursor in CRC cells significantly
      inhibited cell proliferation. Gene expression profiling after miR-137
      transfection discovered novel potential mRNA targets. We validated the
      interaction between miR-137 and LSD-1. Our data indicate that miR-137 acts as a
      tumor suppressor in the colon and is frequently silenced by promoter
      hypermethylation. Methylation silencing of miR-137 in colorectal adenomas
      suggests it to be an early event, which has prognostic and therapeutic
      implications.

PMID- 20682796
TI  - Immunologic consequences of signal transducers and activators of transcription 3
      activation in human squamous cell carcinoma.
AB  - Paracrine cross-talk between tumor cells and immune cells within the tumor
      microenvironment underlies local mechanisms of immune evasion. Signal transducer
      and activator of transcription 3 (STAT3), which is constitutively activated in
      diverse cancer types, is a key regulator of cytokine and chemokine expression in
      murine tumors, resulting in suppression of both innate and adaptive antitumor
      immunity. However, the immunologic effects of STAT3 activation in human cancers
      have not been studied in detail. To investigate how STAT3 activity in human head
      and neck squamous cell carcinoma (HNSCC) might alter the tumor microenvironment
      to enable immune escape, we used small interfering RNA and small-molecule
      inhibitors to suppress STAT3 activity. STAT3 inhibition in multiple primary and
      established human squamous carcinoma lines resulted in enhanced expression and
      secretion of both proinflammatory cytokines and chemokines. Although conditioned
      medium containing supernatants from human HNSCC inhibited lipopolysaccharide
      induced dendritic cell activation in vitro, supernatants from STAT3-silenced
      tumor cells reversed this immune evasion mechanism. Moreover, supernatants from
      STAT3-silenced tumor cells were able to stimulate the migratory behavior of
      lymphocytes from human peripheral blood in vitro. These results show the
      importance of STAT3 activation in regulating the immunomodulatory mediators by
      human tumors and further validate STAT3 as a promising target for therapeutic
      intervention.

PMID- 20682798
TI  - Anti-placental growth factor reduces bone metastasis by blocking tumor cell
      engraftment and osteoclast differentiation.
AB  - Treatment of bone metastases is largely symptomatic and is still an unmet medical
      need. Current therapies mainly target the late phase of tumor-induced osteoclast
      activation and hereby inhibit further metastatic growth. This treatment method
      is, however, less effective in preventing initial tumor engraftment, a process
      that is supposed to depend on the bone microenvironment. We explored whether bone
      derived placental growth factor (PlGF), a homologue of vascular endothelial
      growth factor-A, regulates osteolytic metastasis. Osteogenic cells secrete PlGF,
      the expression of which is enhanced by bone-metastasizing breast tumor cells.
      Selective neutralization of host-derived PlGF by anti-mouse PlGF (alphaPlGF)
      reduced the incidence, number, and size of bone metastases, and preserved bone
      mass. alphaPlGF did not affect metastatic tumor angiogenesis but inhibited
      osteoclast formation by preventing the upregulation of the osteoclastogenic
      cytokine receptor activator of NF-kappaB ligand in osteogenic cells, as well as
      by blocking the autocrine osteoclastogenic activity of PlGF. alphaPlGF also
      reduced the engraftment of tumor cells in the bone and inhibited their
      interaction with matrix components in the metastatic niche. alphaPlGF therefore
      inhibits not only the progression of metastasis but also the settlement of tumor
      in the bone. These findings identify novel properties of PlGF and suggest that
      alphaPlGF might offer opportunities for adjuvant therapy of bone metastasis.

PMID- 20682797
TI  - The histone demethylase JMJD2B is regulated by estrogen receptor alpha and
      hypoxia, and is a key mediator of estrogen induced growth.
AB  - Estrogen receptor alpha (ERalpha) plays an important role in breast cancer.
      Upregulation of HIF-1alpha in ER(alpha)-positive cancers suggests that HIF-1alpha
      may cooperate with ERalpha to promote breast cancer progression and consequently
      affect breast cancer treatment. Here, we show the histone demethylase JMJD2B is
      regulated by both ERalpha and HIF-1alpha, drives breast cancer cell proliferation
      in normoxia and hypoxia, and epigenetically regulates the expression of cell
      cycle genes such as CCND1, CCNA1, and WEE1. We also show that JMJD2B and the
      hypoxia marker CA9 together stratify a subclass of breast cancer patients and
      predict a worse outcome of these breast cancers. Our findings provide a
      biological rationale to support the therapeutic targeting of histone demethylases
      in breast cancer patients.

PMID- 20682799
TI  - Metastasis-associated protein 1 and its short form variant stimulates Wnt1
      transcription through promoting its derepression from Six3 corepressor.
AB  - Although Wnt1 downstream signaling components have been well studied and
      activated in human cancer, the pathways that regulate Wnt1 itself have not been
      explored in depth. Here, we provide gain-of-function, loss-of function, and
      molecular evidence supporting functional interactions between metastasis
      associated protein 1 short-form (MTA1s), metastasis-associated protein 1 (MTA1),
      and Wnt1 signaling components during mammary gland development and tumorigenesis.
      Using multiple model systems involving overexpression or knockdown of MTA1s or
      MTA1, we discovered that MTA1s and MTA1 hyperactivate the Wnt1 pathway due to
      increased expression of Wnt1 transcription. MTA1s and MTA1 physically interact
      with Six3 chromatin, a protein product of which is a direct histone deacetylase
      inhibitor-dependent repressor of Wnt1 transcription. Deletion of the MTA1s and
      MTA1 allele in murine embryonic fibroblasts resulted in the upregulation of Six3
      and downregulation of Wnt signaling. In addition, mammary glands from the
      MTA1s/MTA1(-/-) mice exhibited increased recruitment of Six3 corepressor complex
      to the Wnt1 promoter and inhibition of Wnt1 pathway in mammary glands. These
      findings identify MTA1s and MTA1 as important upstream modifiers of the Wnt1
      transcription, and consequently its functions, by directly inhibiting the
      transcription of Six3, allowing derepression of Wnt1 transcription.

PMID- 20682801
TI  - Bcl9/Bcl9l are critical for Wnt-mediated regulation of stem cell traits in colon
      epithelium and adenocarcinomas.
AB  - Canonical Wnt signaling plays a critical role in stem cell maintenance in
      epithelial homeostasis and carcinogenesis. Here, we show that in the mouse this
      role is critically mediated by Bcl9/Bcl9l, the mammalian homologues of Legless,
      which in Drosophila is required for Armadillo/beta-catenin signaling. Conditional
      ablation of Bcl9/Bcl9l in the intestinal epithelium, where the essential role of
      Wnt signaling in epithelial homeostasis and stem cell maintenance is well
      documented, resulted in decreased expression of intestinal stem cell markers and
      impaired regeneration of ulcerated colon epithelium. Adenocarcinomas with
      aberrant Wnt signaling arose with similar incidence in wild-type and mutant mice.
      However, transcriptional profiles were vastly different: Whereas wild-type tumors
      displayed characteristics of epithelial-mesenchymal transition (EMT) and stem
      cell-like properties, these properties were largely abrogated in mutant tumors.
      These findings reveal an essential role for Bcl9/Bcl9l in regulating a subset of
      Wnt target genes involved in controlling EMT and stem cell-related features and
      suggest that targeting the Bcl9/Bcl9l arm of Wnt signaling in Wnt-activated
      cancers might attenuate these traits, which are associated with tumor invasion,
      metastasis, and resistance to therapy.

PMID- 20682800
TI  - Targeting wild-type and mutant p53 with small molecule CP-31398 blocks the growth
      of rhabdomyosarcoma by inducing reactive oxygen species-dependent apoptosis.
AB  - Rhabdomyosarcoma (RMS) is a common soft-tissue sarcoma of childhood in need of
      more effective therapeutic options. The expression of p53 in RMS is heterogeneous
      such that some tumors are wild-type whereas others are p53 mutant. The small
      molecule CP-31398 modulates both the wild-type and the mutant p53 proteins. Here,
      we show that CP-31398 blocks the growth of RMS cells that have either wild-type
      or mutant p53 status. In wild-type A204 cells, CP-31398 increased the expression
      of p53 and its downstream transcriptional targets, p21 and mdm2; enhanced the
      expression of apoptosis-related proteins; and reduced proliferation biomarkers.
      Flow profiling of CP-31398-treated cells indicated an enhancement in sub-G(0) and
      G(1) populations. CP-31398 inhibited proliferation in a manner associated with co
      induction of SOX9 and p21. Apoptosis induced by CP-31398 occurred with
      translocation of p53 to mitochondria, leading to altered mitochondrial membrane
      potential, cytochrome c release, and reactive oxygen species release. In vivo, CP
      31398 decreased the growth of tumor xenografts composed of wild-type or mutant
      p53 tumor cells, increasing tumor-free host survival. Our findings indicate that
      the ability of CP-31398 to modulate wild-type and mutant p53 results in the
      inhibition of RMS growth and invasiveness.

PMID- 20682803
TI  - Henipavirus: a review of laboratory animal pathology.
AB  - The genus Henipavirus contains two members-Hendra virus (HeV) and Nipah virus
      (NiV)-and each can cause fatal disease in humans and animals. HeV and Niv are
      currently classified as biosafety level 4, and NiV is classified as a category C
      priority pathogen. The aim of this article is to discuss the pathology of
      laboratory animal models of henipavirus infection and to assess their suitability
      as animal models for the development and testing of human therapeutics and
      vaccines. There has been considerable progress in the development of animal
      models for henipavirus disease. Suitable animal models include the golden
      hamster, ferrets, cats, and pigs, which develop disease resembling that observed
      in humans. Guinea pigs are a less reliable model for henipavirus disease, but
      they do develop henipavirus-induced encephalitis. Because human efficacy studies
      with henipaviruses are not permitted, animal studies are critical for the
      development of antiviral therapeutics and vaccines. Current research indicates
      that passive immunotherapy using monoclonal antibodies is protective of ferrets
      against NiV infection and that passive immunotherapy using NiV antibodies
      protects hamsters from HeV. Recombinant vaccines have been used to protect cats
      and pigs against NiV infection. Ribavirin and 6-aza-uridine were able to delay
      but not prevent NiV-induced mortality in hamsters. Further research is needed to
      develop a model and therapy for late-onset henipavirus encephalitis.

PMID- 20682804
TI  - Aerobiology and inhalation exposure to biological select agents and toxins.
AB  - Aerosol is the most likely route of dissemination of biological select agents and
      toxins in a bioterrorist attack, regardless of the natural route of exposure to
      the agent. The use of animal models for testing preventative and therapeutic
      countermeasures requires knowledge of the pathogenesis of disease after
      inhalation exposure. Factors that relate to outcome after respiratory exposure
      include the inherent infectivity and virulence and/or toxicity of the agent in
      the host under investigation, in addition to characteristics of the aerosol
      particle and host that affect the delivered dose of, and host response to, the
      inhaled material. This introductory article discusses the emerging science of
      aerobiology and the unique features of respiratory tract anatomy, physiology, and
      immunology that are relevant to the pathogenesis of aerosolized biothreat agents.

PMID- 20682802
TI  - Dual inhibition of both the epidermal growth factor receptor and erbB2
      effectively inhibits the promotion of skin tumors during two-stage
      carcinogenesis.
AB  - The erbB family of receptor tyrosine kinases are known to play important roles in
      normal epithelial development and epithelial neoplasia. Considerable evidence
      also suggests that signaling through the epidermal growth factor receptor (EGFR)
      plays an important role in multistage skin carcinogenesis in mice; however, less
      is known about the role of erbB2. In this study, to further examine the role of
      both erbB2 and EGFR in epithelial carcinogenesis, we examined the effect of a
      dual erbB2/EGFR tyrosine kinase inhibitor, GW2974, given in the diet on skin
      tumor promotion during two-stage carcinogenesis in wild-type and BK5.erbB2 mice.
      In BK5.erbB2 mice, erbB2 is overexpressed in the basal layer of epidermis and
      leads to heightened sensitivity to skin tumor development. GW2974 effectively
      inhibited skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate in wild
      type and BK5.erbB2 mice, although a more marked effect was seen in BK5.erbB2
      mice. In addition, this inhibitory effect was reversible when GW2974 treatment
      was withdrawn. GW2974 inhibited 12-O-tetradecanoylphorbol-13-acetate-induced
      epidermal hyperproliferation, which correlated with reduced activation of both
      the EGFR and erbB2. These results support the hypothesis that both the EGFR and
      erbB2 play an important role in the development of skin tumors during two-stage
      skin carcinogenesis, especially during the tumor promotion stage. Furthermore,
      the marked sensitivity of BK5.erbB2 mice to the inhibitory effects of GW2974
      during tumor promotion suggest greater efficacy for this compound when erbB2 is
      overexpressed or amplified as an early event in the carcinogenic process.

PMID- 20682805
TI  - Comparative pathology of select agent influenza a virus infections.
AB  - Influenza A virus infections may spread rapidly in human populations and cause
      variable mortality. Two of these influenza viruses have been designated as select
      agents: 1918 H1N1 virus and highly pathogenic avian influenza (HPAI) virus.
      Knowledge of the pathology of these virus infections in humans, other naturally
      infected species, and experimental animals is important to understand the
      pathogenesis of influenza, to design appropriate models for evaluation of medical
      countermeasures, and to make correct diagnoses. The most important complication
      of influenza in humans is viral pneumonia, which often occurs with or is followed
      by bacterial pneumonia. Viremia and extrarespiratory disease are uncommon. HPAI
      viruses, including HPAI H5N1 virus, cause severe systemic disease in galliform
      species as well as in anseriform species and bird species of other orders. HPAI
      H5N1 virus infection also causes severe disease in humans and several species of
      carnivores. Experimental animals are used to model different aspects of influenza
      in humans, including uncomplicated influenza, pneumonia, and virus transmission.
      The most commonly used experimental animal species are laboratory mouse, domestic
      ferret, and cynomolgus macaque. Experimental influenza virus infections are
      performed in various other species, including domestic pig, guinea pig, and
      domestic cat. Each of these species has advantages and disadvantages that need to
      be assessed before choosing the most appropriate model to reach a particular
      goal. Such animal models may be applied for the development of more effective
      antiviral drugs and vaccines to protect humans from the threat of these virus
      infections.

PMID- 20682806
TI  - Animal models of orthopoxvirus infection.
AB  - Smallpox was one of the most devastating diseases known to humanity. Although
      smallpox was eradicated through a historically successful vaccination campaign,
      there is concern in the global community that either Variola virus (VARV), the
      causative agent of smallpox, or another species of Orthopoxvirus could be used as
      agents of bioterrorism. Therefore, development of countermeasures to
      Orthopoxvirus infection is a crucial focus in biodefense research, and these
      efforts rely on the use of various animal models. Smallpox typically presented as
      a generalized pustular rash with 30 to 40% mortality, and although smallpox-like
      syndromes can be induced in cynomolgus macaques with VARV, research with this
      virus is highly restricted; therefore, animal models with other orthopoxviruses
      have been investigated. Monkeypox virus causes a generalized vesiculopustular
      rash in rhesus and cynomolgus macaques and induces fatal systemic disease in
      several rodent species. Ectromelia virus has been extensively studied in mice as
      a model of orthopoxviral infection in its natural host. Intranasal inoculation of
      mice with some strains of vaccinia virus produces fatal bronchopneumonia, as does
      aerosol or intranasal inoculation of mice with cowpox virus. Rabbitpox virus
      causes pneumonia and fatal systemic infections in rabbits and can be naturally
      transmitted between rabbits by an aerosol route similar to that of VARV in
      humans. No single animal model recapitulates all known aspects of human
      Orthopoxvirus infections, and each model has its advantages and disadvantages.
      This article provides a brief review of the Orthopoxvirus diseases of humans and
      the key pathologic features of animal models of Orthopoxvirus infections.

PMID- 20682808
TI  - Training-induced plasticity in the visual cortex of adult rats following visual
      discrimination learning.
AB  - Changes in synaptic efficacy, including long-term potentiation (LTP) and long
      term depression (LTD), provide mechanisms for experience-induced plasticity and
      play a key role in learning processes. Some types of learning (e.g., motor
      learning, fear conditioning) result in LTP and/or LTD-like changes at synapses.
      Here, rats learned to discriminate two visual stimuli, P+ and P-, indicating the
      presence and absence, respectively, of a hidden escape platform in a Y-shaped
      water maze. Following task acquisition, trained rats showed larger amplitude of
      visually evoked potentials (VEPs) in V1 to both stimuli encountered during
      training relative to novel stimuli. Training also resulted in a facilitation of
      LTP induced by theta-burst stimulation (TBS) of thalamic afferents to V1 with no
      effect on depression induced by low-frequency stimulation (LFS). Visual VEP
      enhancement and increased LTP both required that visual stimuli carried some
      significance to the animal, as both effects were absent in control rats exposed
      to the same visual stimuli in the absence of pairing with platform location.
      Together, these experiments show that visual experience can result in a stimulus
      selective response enhancement and an increase in the synaptic modification range
      of V1 synapses, providing a novel example of metaplasticity in circuits of the
      adult cortex.

PMID- 20682807
TI  - Sudden death in a dog after doxorubicin chemotherapy.
AB  - A case is reported of fatal cardiomyopathy in an 8-year-old female German
      Shepherd after standard chemotherapy with doxorubicin for splenic
      hemangiosarcoma. The main gross lesion was a moderate bilateral cardiac
      ventricular dilation with diffusely pale myocardium. Histological analysis
      revealed severe multifocal vacuolar degeneration of cardiomyocytes, myocytolysis,
      myofibril loss, myocardial fibrosis, and edema. Myocardial fiber vacuolization
      and myocytolysis were highly suggestive of doxorubicin cardiotoxicity.

PMID- 20682809
TI  - A brief retraining regulates the persistence and lability of a long-term memory.
AB  - An experience extending the persistence of a memory after training Aplysia
      californica with inedible food also allows a consolidated memory to become
      sensitive to consolidation blockers. Long-term (24 h) memory is initiated by 5
      min of training and is dependent on protein synthesis during the first few hours
      after training. By contrast, a more persistent (48 h) memory is dependent on a
      longer training session and on a later round of protein synthesis. When presented
      24 h after training, a 3-min training that produces no memory alone can cause a
      memory that would have persisted for only 24 h to persist for 48 h. After a 48 h
      memory has been consolidated, 3 min of training also makes the memory sensitive
      to a protein-synthesis inhibitor. These findings suggest that a function of
      allowing a consolidated memory to become sensitive to blockers of protein
      synthesis may be to allow the memory to become more persistent.

PMID- 20682810
TI  - New behavioral protocols to extend our knowledge of rodent object recognition
      memory.
AB  - Animals often show an innate preference for novelty. This preference facilitates
      spontaneous exploration tasks of novelty discrimination (recognition memory). In
      response to limitations with standard spontaneous object recognition procedures
      for rodents, a new task ("bow-tie maze") was devised. This task combines features
      of delayed nonmatching-to-sample with spontaneous exploration. The present study
      explored aspects of object recognition in the bow-tie maze not amenable to
      standard procedures. Two rat strains (Lister Hooded, Dark Agouti) displayed very
      reliable object recognition in both the light and dark, with the Lister Hooded
      strain showing superior performance (Experiment 1). These findings reveal the
      potential contribution of tactile and odor cues in object recognition. As the bow
      tie maze task permits multiple trials within a session, it was possible to derive
      forgetting curves both within-session and between-sessions (Experiment 1). In
      Experiment 2, rats with hippocampal or fornix lesions performed at normal levels
      on the basic version of the recognition task, contrasting with the marked
      deficits previously seen after perirhinal cortex lesions. Next, the training
      protocol was adapted (Experiment 3), and this modified version was used
      successfully with mice (Experiment 4). The overall findings demonstrate the
      efficacy of this new behavioral task and advance our understanding of object
      recognition.

PMID- 20682811
TI  - Misconceptions about gene-environment interactions in psychiatry.
AB  - Misunderstandings surrounding the study of gene-environment interactions are very
      common. Given the large increase in the number of studies examining interactions
      in recent years, this raises serious concerns about the value of time and
      resources spent in these endeavours. In this article we discuss why, despite
      frequent claims to the contrary, studies of gene-environment interactions are
      very unlikely to enhance our understanding of disease aetiology or prevention.

PMID- 20682812
TI  - Evidence based mental health and Web 2.0.

PMID- 20682813
TI  - Moderate or high physical activity lowers the risk of cognitive impairment in
      older people.

PMID- 20682814
TI  - High mortality and reduced quality of life in people who have presented to
      hospital for self-harm in the UK.

PMID- 20682815
TI  - Angiotensin receptor blockers associated with decreased incidence and progression
      of dementia in older men with cardiovascular disease.

PMID- 20682816
TI  - Review: ADHD impairs quality of life, but children and young people with ADHD
      perceive less impairment than parents.

PMID- 20682817
TI  - The EPOS prediction model improves ability to predict transition to first episode
      psychosis in individuals at high risk.

PMID- 20682818
TI  - Past or current drug or alcohol use disorders increase the likelihood of a switch
      from depressive to manic, mixed or hypomanic states in patients with bipolar
      disorder.

PMID- 20682819
TI  - A GP training package for the treatment of anxiety disorders is not cost
      effective.

PMID- 20682820
TI  - Injectable diacetylmorphine is more effective than oral methadone in the
      treatment of chronic relapsing opioid dependence.

PMID- 20682821
TI  - Escitalopram may improve some cognitive functions after stroke in non-depressed
      patients.

PMID- 20682822
TI  - Brief, personality-targeted coping-skills intervention reduces onset and
      escalation of drug misuse.

PMID- 20682823
TI  - Compared with fluoxetine monotherapy, mirtazapine plus venlafaxine or fluoxetine
      increase remission but not response in patients with major depressive disorder.

PMID- 20682824
TI  - Second generation antipsychotics are not superior in relieving family burden in
      schizophrenia compared with the first generation antipsychotic perphenazine.

PMID- 20682825
TI  - Bifrontal, bitemporal and right unilateral ECT electrode placement are similarly
      effective for reducing depressive symptoms.

PMID- 20682826
TI  - Review: evidence on the effect of antiepileptics on recurrent aggression
      inconclusive.

PMID- 20682827
TI  - A stepped care programme for depressive or anxiety disorders offers good value
      for money.

PMID- 20682828
TI  - Quetiapine is effective in the treatment of adults in the acute phase of bipolar
      depression.

PMID- 20682829
TI  - Current use of venlafaxine not associated with excess risk of sudden cardiac
      death or near death compared with fluoxetine, citalopram or dosulepin.

PMID- 20682830
TI  - Antipsychotic polypharmacy is not associated with increased mortality from
      natural causes in patients with schizophrenia compared to monotherapy.

PMID- 20682831
TI  - Cholinesterase inhibitor treatment may double the risk of hospitalisation for
      bradycardia.

PMID- 20682832
TI  - Extremely preterm children at increased risk of autism spectrum disorders.

PMID- 20682833
TI  - Binge drinking frequent among adults aged 50 years and older.

PMID- 20682834
TI  - Review: befriending modestly reduces depressive symptoms in varied populations.

PMID- 20682835
TI  - Review: exercise programmes reduce anxiety symptoms in sedentary patients with
      chronic illnesses.

PMID- 20682836
TI  - The PHQ-9 works well as a screening but not diagnostic instrument for depressive
      disorder.

PMID- 20682837
TI  - Abscisic acid increases Arabidopsis ABI5 transcription factor levels by promoting
      KEG E3 ligase self-ubiquitination and proteasomal degradation.
AB  - The Arabidopsis thaliana RING-type E3 ligase KEEP ON GOING (KEG) is a negative
      regulator of abscisic acid (ABA) signaling. Seedlings homozygous for T-DNA
      insertions in KEG accumulate high levels of the ABA-responsive transcription
      factor ABSCISIC ACID-INSENSITIVE5 (ABI5). Here, we demonstrate that KEG E3 ligase
      activity is required for the regulation of ABI5 abundance. KEG ubiquitinates ABI5
      in vitro, and a functional KEG RING domain is required to restore the levels of
      ABI5 in keg-1 to that of the wild type. Overexpression of KEG leads to ABA
      insensitivity, which correlates with KEG protein levels. In the presence of ABA,
      ABI5 levels increase drastically via a decrease in ubiquitin-meditated
      proteasomal degradation. Our results indicate that ABA promotes ABI5 accumulation
      by inducing the ubiquitination and proteasomal degradation of KEG. A functional
      RING domain is required for the ABA-induced degradation of KEG, suggesting that
      the loss is due to self-ubiquitination. Mutations within KEG's kinase domain or
      treatments with kinase inhibitors prohibit the ABA-induced ubiquitination and
      degradation of KEG, indicating that phosphorylation, possibly self
      phosphorylation, is involved in the ABA regulation of KEG protein levels. We
      discuss a model for how ABA may negatively regulate KEG protein abundance,
      leading to accumulation of ABI5 and ABA-dependent cellular responses.

PMID- 20682838
TI  - Kinase-mediated quasi-dimers of EGFR.
AB  - Ligand-induced dimerization of the epidermal growth factor receptor (ErbB-1/EGFR)
      involves conformational changes that expose an extracellular dimerization
      interface. Subsequent alterations within the cytoplasmic kinase domain, which
      culminate in tyrosine phosphorylation, are less understood. Our study addressed
      this question by using two strategies: a chimeric receptor approach employed ErbB
      3, whose defective kinase domain was replaced by the respective part of EGFR. The
      implanted full-length kinase, unlike its subdomains, conferred dimerization and
      catalysis. The data infer that the kinase function of EGFR is restrained by the
      carboxyl tail; once grafted distally to the ectopic tail of ErbB-3, the kinase
      domain acquires quasi-dimerization and activation. In an attempt to alternatively
      refold the cytoplasmic tail, our other approach employed kinase inhibitors.
      Biophysical measurements and covalent cross-linking analyses showed that
      inhibitors targeting the active conformation of EGFR, in contrast to a compound
      recognizing the inactive conformation, induce quasi-dimers in a manner similar to
      the chimeric ErbB-3 molecule. Collectively, these observations unveil kinase
      domain-mediated quasi-dimers, which are regulated by an autoinhibitory carboxyl
      tail. On the basis of these observations, we propose that quasi-dimers precede
      formation of ligand-induced, fully active dimers, which are stabilized by both
      extracellular and intracellular receptor-receptor interactions.

PMID- 20682839
TI  - Identification of the ectonucleotidases expressed in mouse, rat, and human
      Langerhans islets: potential role of NTPDase3 in insulin secretion.
AB  - Extracellular nucleotides and adenosine regulate endocrine pancreatic functions
      such as insulin secretion by Langerhans islet beta-cells via the activation of
      specific P2 and P1 receptors. Membrane-bound ectonucleotidases regulate the local
      concentration of these ligands and consequently control the activation of their
      receptors. The objective of this study was to identify and localize the major
      ectonucleotidases, namely NTPDases and ecto-5'-nucleotidase, present in the
      endocrine pancreas. In addition, the potential implication of ecto-ATPase
      activity on insulin secretion was investigated in the rat beta-cell line INS-1
      (832/13). The localization of ectonucleotidase activity and protein was carried
      out in situ by enzyme histochemistry and immunolocalization in mouse, rat, and
      human pancreas sections. NTPDase1 was localized in all blood vessels and acini,
      and NTPDase2 was localized in capillaries of Langerhans islets and in peripheral
      conjunctive tissue, whereas NTPDase3 was detected in all Langerhans islet cell
      types. Interestingly, among the mammalian species tested, ecto-5'-nucleotidase
      was present only in rat Langerhans islet cells, where it was coexpressed with
      NTPDase3. Notably, the inhibition of NTPDase3 activity by BG0136 and NF279
      facilitated insulin release from INS-1 (832/13) cells under conditions of low
      glycemia, probably by affecting P2 receptor activation. NTPDase3 activity also
      regulated the inhibitory effect of exogenous ATP in the presence of a high
      glucose concentration most likely by controlling adenosine production. In
      conclusion, all pancreatic endocrine cells express NTPDase3 that was shown to
      modulate insulin secretion in rat INS-1 (832/13) beta-cells. Ecto-5'-nucleotidase
      is expressed in rat Langerhans islet cells but absent in human and mouse
      endocrine cells.

PMID- 20682840
TI  - Estrogen sulfotransferase regulates body fat and glucose homeostasis in female
      mice.
AB  - Estrogen regulates fat mass and distribution and glucose metabolism. We have
      previously found that estrogen sulfotransferase (EST), which inactivates estrogen
      through sulfoconjugation, was highly expressed in adipose tissue of male mice and
      induced by testosterone in female mice. To determine whether inhibition of
      estrogen in female adipose tissue affects adipose mass and metabolism, we
      generated transgenic mice expressing EST via the aP2 promoter. As expected, EST
      expression was increased in adipose tissue as well as macrophages. Parametrial
      and subcutaneous inguinal adipose mass and adipocyte size were significantly
      reduced in EST transgenic mice, but there was no change in retroperitoneal or
      brown adipose tissue. EST overexpression decreased the differentiation of primary
      adipocytes, and this was associated with reductions in the expression of
      peroxisome proliferator-activated receptor-gamma, fatty acid synthase, hormone
      sensitive lipase, lipoprotein lipase, and leptin. Serum leptin levels were
      significantly lower in EST transgenic mice, whereas total and high-molecular
      weight adiponectin levels were not different in transgenic and wild-type mice.
      Glucose uptake was blunted in parametrial adipose tissue during hyperinsulinemic
      euglycemic clamp in EST transgenic mice. In contrast, hepatic insulin sensitivity
      was improved but muscle insulin sensitivity did not change in EST transgenic
      mice. These results reveal novel effects of EST on adipose tissue and glucose
      homeostasis in female mice.

PMID- 20682841
TI  - Experimentally induced gestational androgen excess disrupts glucoregulation in
      rhesus monkey dams and their female offspring.
AB  - Discrete fetal androgen excess during early gestation in rhesus monkeys (Macaca
      mulatta) promotes endocrine antecedents of adult polycystic ovary syndrome (PCOS)
      like traits in female offspring. Because developmental changes promoting such
      PCOS-like metabolic dysfunction remain unclear, the present study examined time
      mated, gravid rhesus monkeys with female fetuses, of which nine gravid females
      received 15 mg of testosterone propionate (TP) subcutaneously daily from 40 to 80
      days (first to second trimesters) of gestation [term, mean (range): 165 (155-175)
      days], whereas an additional six such females received oil vehicle injections
      over the same time interval. During gestation, ultrasonography quantified fetal
      growth measures and was used as an adjunct for fetal blood collections. At term,
      all fetuses were delivered by cesarean section for postnatal studies. Blood
      samples were collected from dams and infants for glucose, insulin, and total free
      fatty acid (FFA) determinations. TP injections transiently accelerated maternal
      weight gain in dams, very modestly increased head diameter of prenatally
      androgenized (PA) fetuses, and modestly increased weight gain in infancy compared
      with concurrent controls. Mild to moderate glucose intolerance, with increased
      area-under-the-curve circulating insulin values, occurred in TP-injected dams
      during an intravenous glucose tolerance test in the early second trimester.
      Moreover, reduced circulating FFA levels occurred in PA fetuses during a third
      trimester intravenous glucagon-tolbutamide challenge (140 days gestation),
      whereas excessive insulin sensitivity and increased insulin secretion relative to
      insulin sensitivity occurred in PA infants during an intravenous glucose
      tolbutamide test at ~1.5 mo postnatal age. Data from these studies suggest that
      experimentally induced fetal androgen excess may result in transient
      hyperglycemic episodes in the intrauterine environment that are sufficient to
      induce relative increases in pancreatic function in PA infants, suggesting in
      this nonhuman primate model that differential programming of insulin action and
      secretion may precede adult metabolic dysfunction.

PMID- 20682842
TI  - Age disrupts androgen receptor-modulated negative feedback in the gonadal axis in
      healthy men.
AB  - Testosterone (T) exerts negative feedback on the hypothalamo-pituitary (GnRH-LH)
      unit, but the relative roles of the CNS and pituitary are not established. We
      postulated that relatively greater LH responses to flutamide (brain-permeant
      antiandrogen) than bicalutamide (brain-impermeant antiandrogen) should reflect
      greater feedback via CNS than pituitary/peripheral androgen receptor-dependent
      pathways. To this end, 24 healthy men ages 20-73 yr, BMI 21-32 kg/m2,
      participated in a prospective, placebo-controlled, randomized, double-blind
      crossover study of the effects of antiandrogen control of pulsatile, basal, and
      entropic (pattern regularity) measurements of LH secretion. Analysis of
      covariance revealed that flutamide but not bicalutamide 1) increased pulsatile LH
      secretion (P = 0.003), 2) potentiated the age-related abbreviation of LH
      secretory bursts (P = 0.025), 3) suppressed incremental GnRH-induced LH release
      (P = 0.015), and 4) decreased the regularity of GnRH-stimulated LH release (P =
      0.012). Furthermore, the effect of flutamide exceeded that of bicalutamide in 1)
      raising mean LH (P = 0.002) and T (P = 0.017) concentrations, 2) accelerating LH
      pulse frequency (P = 0.013), 3) amplifying total (basal plus pulsatile) LH (P =
      0.002) and T (P < 0.001) secretion, 4) shortening LH secretory bursts (P =
      0.032), and 5) reducing LH secretory regularity (P < 0.001). Both flutamide and
      bicalutamide elevated basal (nonpulsatile) LH secretion (P < 0.001). These data
      suggest the hypothesis that topographically selective androgen receptor pathways
      mediate brain-predominant and pituitary-dependent feedback mechanisms in healthy
      men.

PMID- 20682843
TI  - SK3 channel expression during pregnancy is regulated through estrogen and Sp
      factor-mediated transcriptional control of the KCNN3 gene.
AB  - Overexpression of the small-conductance calcium-activated K(+) channel 3 (SK3) in
      transgenic mice compromises parturition, suggesting that the SK3 channel plays a
      role in pregnancy. In wild-type mouse myometrium, expression of SK3 transcript
      and protein is significantly reduced during pregnancy, but the mechanism(s)
      responsible for this attenuation of channel expression is unknown. The promoter
      region of the SK3-encoding mouse KCNN3 gene contains two binding sites for
      specificity protein (Sp) transcription factors, two of which are expressed in the
      uterus: Sp1, which enhances gene transcription in response to estrogen; and Sp3,
      which competes for the same binding motif as Sp1 and can repress gene expression.
      We investigated the hypothesis that Sp1 and Sp3 regulate SK3 channel expression
      during pregnancy. In mouse myometrium, Sp1 expression was reduced during late
      gestation, whereas Sp3 expression levels were constant throughout pregnancy.
      Using a reporter system, we found that Sp1 overexpression resulted in a
      significant increase in SK3 promoter activation and that Sp3 cotransfection
      reduced promoter activation to basal levels. These findings indicate that Sp3
      outcompetes Sp1 to decrease SK3 transcription. To determine whether high levels
      of estrogen in vivo can affect the regulation of SK3 protein levels by Sp
      factors, ovariectomized mice were implanted with a 17beta-estradiol or placebo
      pellet for 3 wk; estrogen-treated mice had reduced uterine SK3 protein expression
      compared with placebo-treated counterparts. In human myometrial cells
      overexpressing Sp1, estrogen treatment stimulated expression of the SK3
      transcript. Overall, our findings indicate that Sp1 and Sp3 compete to regulate
      SK3 channel expression during pregnancy in response to stimulation by estrogen.

PMID- 20682844
TI  - Activation and repression of glucose-stimulated ChREBP requires the concerted
      action of multiple domains within the MondoA conserved region.
AB  - Carbohydrate response element-binding protein (ChREBP) is a glucose-dependent
      transcription factor that stimulates the expression of glycolytic and lipogenic
      genes in mammals. Glucose regulation of ChREBP has been mapped to its conserved
      NH(2)-terminal region of 300 amino acids, designated the MondoA conserved region
      (MCR). Within the MCR, five domains (MCR1-5) have a particularly high level of
      conservation and are likely to be important for glucose regulation. We carried
      out a large-scale deletion and substitution mutational analysis of the MCR domain
      of ChREBP. This analysis revealed that MCRs 1-4 function in a concerted fashion
      to repress ChREBP activity in basal (nonstimulatory) conditions. Deletion of the
      entire MCR1-4 segment or the combination of four specific point mutations located
      across this region leads to a highly active, glucose-independent form of ChREBP.
      However, deletion of any individual MCR domain and the majority of point
      mutations throughout MCR1-4 rendered ChREBP inactive. These observations suggest
      that the MCR1-4 region interacts with an additional coregulatory factor required
      for activation. This possibility is supported by the observation that the MCR1-4
      region can compete for activity with wild-type ChREBP in stimulatory conditions.
      In contrast, mutations in the MCR5 domain result in increased activity,
      suggesting that this domain may be the target of intramolecular repression in
      basal conditions. Thus, the MCR domains act in a complex and coordinated manner
      to regulate ChREBP activity in response to glucose.

PMID- 20682845
TI  - Circadian variations in gene expression in rat abdominal adipose tissue and
      relationship to physiology.
AB  - Circadian rhythms occur in all levels of organization from expression of genes to
      complex physiological processes. Although much is known about the mechanism of
      the central clock in the suprachiasmatic nucleus, the regulation of clocks
      present in peripheral tissues as well as the genes regulated by those clocks is
      still unclear. In this study, the circadian regulation of gene expression was
      examined in rat adipose tissue. A rich time series involving 54 animals
      euthanized at 18 time points within the 24-h cycle (12:12 h light-dark) was
      performed. mRNA expression was examined with Affymetrix gene array chips and
      quantitative real-time PCR, along with selected physiological measurements.
      Transcription factors involved in the regulation of central rhythms were
      examined, and 13 showed circadian oscillations. Mining of microarray data
      identified 190 probe sets that showed robust circadian oscillations. Circadian
      regulated probe sets were further parsed into seven distinct temporal clusters,
      with >70% of the genes showing maximum expression during the active/dark period.
      These genes were grouped into eight functional categories, which were examined
      within the context of their temporal expression. Circadian oscillations were also
      observed in plasma leptin, corticosterone, insulin, glucose, triglycerides, free
      fatty acids, and LDL cholesterol. Circadian oscillation in these physiological
      measurements along with the functional categorization of these genes suggests an
      important role for circadian rhythms in controlling various functions in white
      adipose tissue including adipogenesis, energy metabolism, and immune regulation.

PMID- 20682847
TI  - Mouse embryonic phenotyping by morphometric analysis of MR images.
AB  - A new method is described for automatic detection of subtle morphological
      phenotypes in mouse embryos. Based on high-resolution magnetic resonance imaging
      scanning and nonlinear image alignment, this method is demonstrated by comparing
      the morphology of two inbred strains, C57BL/6J and 129Sv/S1ImJ, at 15.5 days
      postconception. Mouse embryo morphology was found to be highly amenable to this
      kind of analysis with very low levels (on average 110 MUm) of residual anatomical
      variation within strains after linear differences in pose and scale are removed.
      Mapping of local size differences showed that C57BL/6J embryos were larger than
      129Sv/S1ImJ embryos, although these differences were not uniformly distributed
      across the anatomy. Expressed in terms of organ volumes, heart and lung were
      larger in C57BL/6J embryos, while brain and liver were comparable in volume
      between strains. The positive relationship between organ size and embryo size was
      consistent for the two strains but differed by organ, with the brain and liver
      being the least variable. Together these findings suggest the power of this
      technique for detecting subtle phenotypic differences arising from mutated genes.

PMID- 20682846
TI  - Expression and distribution of voltage-gated ion channels in ferret sinoatrial
      node.
AB  - Spontaneous diastolic depolarization in the sinoatrial (SA) node enables it to
      serve as pacemaker of the heart. The variable cell morphology within the SA node
      predicts that ion channel expression would be heterogeneous and different from
      that in the atrium. To evaluate ion channel heterogeneity within the SA node, we
      used fluorescent in situ hybridization to examine ion channel expression in the
      ferret SA node region and atrial appendage. SA nodal cells were distinguished
      from surrounding cardiac myocytes by expression of the slow (SA node) and cardiac
      (surrounding tissue) forms of troponin I. Nerve cells in the sections were
      identified by detection of GAP-43 and cytoskeletal middle neurofilament.
      Transcript expression was characterized for the 4 hyperpolarization-activated
      cation channels, 6 voltage-gated Na(+) channels, 3 voltage-gated Ca(2+) channels,
      24 voltage-gated K(+) channel alpha-subunits, and 3 ancillary subunits. To ensure
      that transcript expression was representative of protein expression,
      immunofluorescence was used to verify localization patterns of voltage-dependent
      K(+) channels. Colocalizations were performed to observe any preferential
      patterns. Some overlapping and nonoverlapping binding patterns were observed.
      Measurement of different cation channel transcripts showed heterogeneous
      expression with many different patterns of expression, attesting to the
      complexity of electrical activity in the SA node. This study provides insight
      into the possible role ion channel heterogeneity plays in SA node pacemaker
      activity.

PMID- 20682848
TI  - Disease and phenotype gene set analysis of disease-based gene expression in mouse
      and human.
AB  - The genetic contributions to common disease and complex disease phenotypes are
      pleiotropic, multifactorial, and combinatorial. Gene set analysis is a
      computational approach used in the analysis of microarray data to rapidly query
      gene combinations and multifactorial processes. Here we use novel gene sets based
      on population-based human genetic associations in common human disease or
      experimental genetic mouse models to analyze disease-related microarray studies.
      We developed a web-based analysis tool that uses these novel disease- and
      phenotype-related gene sets to analyze microarray-based gene expression data.
      These gene sets show disease and phenotype specificity in a species-specific and
      cross-species fashion. In this way, we integrate population-based common human
      disease genetics, mouse genetically determined phenotypes, and disease or
      phenotype structured ontologies, with gene expression studies relevant to human
      disease. This may aid in the translation of large-scale high-throughput datasets
      into the context of clinically relevant disease phenotypes.

PMID- 20682849
TI  - In vitro characterization of T-type calcium channel antagonist TTA-A2 and in vivo
      effects on arousal in mice.
AB  - T-type calcium channels have been implicated in many behaviorally important
      neurophysiological processes, and altered channel activity has been linked to the
      pathophysiology of neurological disorders such as insomnia, epilepsy, Parkinson's
      disease, depression, schizophrenia, and pain. We have previously identified a
      number of potent and selective T-type channel antagonists (Barrow et al., 2007;
      Shipe et al., 2008; Yang et al., 2008). Here we describe the properties of the
      antagonist TTA-A2 [2-(4-cyclopropylphenyl)-N-((1R)-1-{5-[(2,2,2
      trifluoroethyl)oxo]-pyridin-2-yl}ethyl)acetamide], assessed in patch-clamp
      experiments. TTA-A2 blocks T-type channels (Ca(v)3.1, 3.2, 3.3) voltage
      dependently and with high potency (IC(50) ~100 nM). Stimulation at 3 Hz revealed
      additional use dependence of inhibition. A hyperpolarized shift of the channel
      availability curve and delayed channel recovery from inactivation suggest that
      the compound preferentially interacts with and stabilizes inactivated channels.
      The compound showed a ~300-fold selectivity for Ca(v)3 channels over high-voltage
      activated calcium channels. Inhibitory effects on native T-type currents were
      confirmed in brain slice recordings from the dorsal lateral geniculate nucleus
      and the subthalamic nucleus. Furthermore, we demonstrate that in vivo T-type
      channel inhibition by TTA-A2 suppresses active wake and promotes slow-wave sleep
      in wild-type mice but not in mice lacking both Ca(v)3.1 and Ca(v)3.3, suggesting
      the selective effect of TTA-A2 on recurrent thalamocortical network activity. The
      discovery of the potent and selective T-type channel antagonist TTA-A2 has
      enabled us to study the in vivo effects of pharmacological T-channel inhibition
      on arousal in mice, and it will help to explore the validity of these channels as
      potential drug targets for sleep-related and other neurological diseases.

PMID- 20682850
TI  - Risk of skeletal-related events in patients with advanced prostate cancer treated
      with pamidronate or zoledronic acid.
AB  - BACKGROUND: Pamidronate and zoledronic acid are used for the prevention of
      skeletal-related events (SREs) in patients with advanced solid tumors,
      particularly breast and prostate cancers. There have been no head-to-head
      clinical trials comparing pamidronate and zoledronic acid among patients with
      advanced prostate cancer. OBJECTIVE: To estimate the risk of developing an SRE
      among men with metastatic prostate cancer after being treated with either
      pamidronate or zoledronic acid. METHODS: A retrospective cohort study was
      conducted, using data from Kaiser Permanente's Southern California Region. The
      cohort included men aged > or = 18 years diagnosed with prostate cancer from 1998
      to 2004 who received at least 1 infusion of either pamidronate or zoledronic acid
      after their cancer diagnosis. Patients receiving both drugs and those with a
      documented SRE prior to diagnosis were excluded. The primary outcome of SREs was
      defined using diagnosis codes for fractures, spinal cord compression, radiation
      to bone, and hypercalcemia of malignancy. Secondary outcomes were deterioration
      in renal function, based on serum creatinine laboratory results, and mortality.
      Multivariate logistic regression was used to predict SREs and mortality risk for
      pamidronate compared to zoledronic acid. The proportion of patients with renal
      function deterioration was analyzed using chi(2) tests. RESULTS: The cohort
      included 118 patients treated with pamidronate and 274 treated with zoledronic
      acid. Results showed no significant difference in risk of SREs for pamidronate
      versus zoledronic acid (OR 0.99; 95% CI 0.59 to 1.67; p = 0.98). No significant
      difference was found in renal function deterioration (chi(2) 2.08; p = 0.15) or
      mortality (OR 0.71; 95% CI 0.43 to 1.17; p = 0.18). CONCLUSIONS: For patients
      with prostate cancer, the choice between these 2 bisphosphonates must be balanced
      between the shorter infusion time of zoledronic acid versus its increased costs.
      We found no evidence for a difference in outcomes; therefore, pamidronate is an
      effective choice where clinic capacity permits.

PMID- 20682851
TI  - Comment: effect of scheduling tramadol as a controlled substance on poison center
      exposures to tramadol.

PMID- 20682852
TI  - siRNA silencing of PD-L1 and PD-L2 on dendritic cells augments expansion and
      function of minor histocompatibility antigen-specific CD8+ T cells.
AB  - Tumor relapse after human leukocyte antigen-matched allogeneic stem cell
      transplantation (SCT) remains a serious problem, despite the long-term presence
      of minor histocompatibility antigen (MiHA)-specific memory T cells. Dendritic
      cell (DC)-based vaccination boosting MiHA-specific T-cell immunity is an
      appealing strategy to prevent or counteract tumor recurrence, but improvement is
      necessary to increase the clinical benefit. Here, we investigated whether
      knockdown of programmed death ligand 1 (PD-L1) and PD-L2 on monocyte-derived DCs
      results in improved T-cell activation. Electroporation of single siRNA sequences
      into immature DCs resulted in efficient, specific, and long-lasting knockdown of
      PD-L1 and PD-L2 expression. PD-L knockdown DCs strongly augmented interferon
      gamma and interleukin-2 production by stimulated T cells in an allogeneic mixed
      lymphocyte reaction, whereas no effect was observed on T-cell proliferation.
      Moreover, we demonstrated that PD-L gene silencing, especially combined PD-L1 and
      PD-L2 knockdown, resulted in improved proliferation and cytokine production of
      keyhole limpet hemocyanin-specific CD4(+) T cells. Most importantly, PD-L
      knockdown DCs showed superior potential to expand MiHA-specific CD8(+) effector
      and memory T cells from leukemia patients early after donor lymphocyte infusion
      and later during relapse. These data demonstrate that PD-L siRNA electroporated
      DCs are highly effective in enhancing T-cell proliferation and cytokine
      production, and are therefore attractive cells for improving the efficacy of DC
      vaccines in cancer patients.

PMID- 20682853
TI  - Regulation by SIRPalpha of dendritic cell homeostasis in lymphoid tissues.
AB  - The molecular basis for regulation of dendritic cell (DC) development and
      homeostasis remains unclear. Signal regulatory protein alpha (SIRPalpha), an
      immunoglobulin superfamily protein that is predominantly expressed in DCs,
      mediates cell-cell signaling by interacting with CD47, another immunoglobulin
      superfamily protein. We now show that the number of CD11c(high) DCs (conventional
      DCs, or cDCs), in particular, that of CD8-CD4+ (CD4+) cDCs, is selectively
      reduced in secondary lymphoid tissues of mice expressing a mutant form of
      SIRPalpha that lacks the cytoplasmic region. We also found that SIRPalpha is
      required intrinsically within cDCs or DC precursors for the homeostasis of
      splenic CD4+ cDCs. Differentiation of bone marrow cells from SIRPalpha mutant
      mice into DCs induced by either macrophage-granulocyte colony-stimulating factor
      or Flt3 ligand in vitro was not impaired. Although the accumulation of the
      immediate precursors of cDCs in the spleen was also not impaired, the half-life
      of newly generated splenic CD4+ cDCs was markedly reduced in SIRPalpha mutant
      mice. Both hematopoietic and nonhematopoietic CD47 was found to be required for
      the homeostasis of CD4+ cDCs and CD8-CD4- (double negative) cDCs in the spleen.
      SIRPalpha as well as its ligand, CD47, are thus important for the homeostasis of
      CD4+ cDCs or double negative cDCs in lymphoid tissues.

PMID- 20682854
TI  - In vivo RNAi-mediated silencing of TAK1 decreases inflammatory Th1 and Th17 cells
      through targeting of myeloid cells.
AB  - Cells from the mononuclear phagocyte system (MPS) act as systemic and local
      amplifiers that contribute to the progression of chronic inflammatory disorders.
      Transforming growth factor-beta-activated kinase 1 (TAK1) is a pivotal upstream
      mitogen-activated protein kinase-kinase-kinase acting as a mediator of cytokine
      expression. It remains critical to determine in vivo the implication of TAK1 in
      controlling the innate immune system. Here, we describe a vehicle tailored to
      selectively deliver siRNAs into MPS cells after intravenous administration, and
      validate in vivo the potential of the RNAi-mediated TAK1 knock down for
      immunomodulation. In a mouse model of immune-mediated inflammatory disorder, we
      show that anti-TAK1 siRNA lipoplexes efficiently alleviate inflammation, severely
      impair the downstream c-Jun N-terminal kinase and nuclear factor-kappaB signaling
      pathways, and decrease the expression of proinflammatory mediators. Importantly,
      the systemic TAK1 gene silencing decreases the frequency of Th1 and Th17 cells,
      both mediating autoimmunity in experimental arthritis, demonstrating the
      immunomodulatory potential of TAK1. Finally, in vitro inhibition of TAK1 in
      myeloid cells decreases interferon-gamma-producing T cells, suggesting that a
      delivery system able to target MPS cells and to silence TAK1 impacts on
      pathogenic T effector cells in autoimmunity.

PMID- 20682855
TI  - An antibody against the colony-stimulating factor 1 receptor depletes the
      resident subset of monocytes and tissue- and tumor-associated macrophages but
      does not inhibit inflammation.
AB  - The development of the mononuclear phagocyte system requires macrophage colony
      stimulating factor (CSF-1) signaling through the CSF-1 receptor (CSF1R, CD115).
      We examined the effect of an antibody against CSF1R on macrophage homeostasis and
      function using the MacGreen transgenic mouse (csf1r-enhanced green fluorescent
      protein) as a reporter. The administration of a novel CSF1R blocking antibody
      selectively reduced the CD115(+)Gr-1(neg) monocyte precursor of resident tissue
      macrophages. CD115(+)Gr-1(+) inflammatory monocytes were correspondingly
      increased, supporting the view that monocytes are a developmental series. Within
      tissue, the antibody almost completely depleted resident macrophage populations
      in the peritoneum, gastrointestinal tract, liver, kidney, and skin, but not in
      the lung or female reproductive organs. CSF1R blockade reduced the numbers of
      tumor-associated macrophages in syngeneic tumor models, suggesting that these
      cells are resident type macrophages. Conversely, it had no effect on inflammatory
      monocyte recruitment in models, including lipopolysaccharide-induced lung
      inflammation, wound healing, peritonitis, and severe acute graft-versus-host
      disease. Depletion of resident tissue macrophages from bone marrow
      transplantation recipients actually resulted in accelerated pathology and
      exaggerated donor T-cell activation. The data indicate that CSF1R signaling is
      required only for the maturation and replacement of resident-type monocytes and
      tissue macrophages, and is not required for monocyte production or inflammatory
      function.

PMID- 20682856
TI  - Colonic leishmaniasis followed by liver transplantation.

PMID- 20682857
TI  - First case of heterochthonous subconjunctival dirofilariasis described in Poland.

PMID- 20682858
TI  - Short-term global health research projects by US medical students: ethical
      challenges for partnerships.
AB  - Recent interest in global health among medical students has grown drastically,
      and many students now spend time abroad conducting short-term research projects
      in low-resource settings. These short-term stints in developing countries present
      important ethical challenges to US-based students and their medical schools as
      well as the institutions that host such students abroad. This paper outlines some
      of these ethical issues and puts forth recommendations for ethically mindful
      short-term student research.

PMID- 20682859
TI  - Nigeria's triumph: dracunculiasis eradicated.
AB  - This report describes how Nigeria, a country that at one time had the highest
      number of cases of dracunculiasis (Guinea worm disease) in the world, reduced the
      number of cases from more than 653,000 in 1988 to zero in 2009, despite numerous
      challenges. Village-based volunteers formed the foundation of the program, which
      used health education, cloth filters, vector control, advocacy for safe water,
      voluntary isolation of patients, and monitored program interventions and cases
      reported monthly. Other factors in the program's success were strong governmental
      support, advocacy by a former head of state of Nigeria, technical and financial
      assistance by The Carter Center, the U.S. Centers for Disease Control and
      Prevention, the United Nations Children's Fund, the World Health Organization,
      and many other partners and donors. The estimated cost of the Nigerian program
      during 1988-2009 is $37.5 million, not including funding for water supply
      projects or salaries of Nigerian governmental workers.

PMID- 20682860
TI  - Report on the 6th African Society of Human Genetics (AfSHG) Meeting, March 12-15,
      2009, Yaounde, Cameroon.
AB  - The African Society of Human Genetics (AfSHG), founded in 2003 with its inaugural
      meeting in Accra, Ghana,1 has the stated missions of (1) disseminating
      information about human genetics research in Africa, (2) establishing a
      mentorship network providing educational resources, including the development of
      appropriate technology transfer, (3) providing advocacy for human genetic
      research in Africa, and (4) encouraging collaborative research. Despite its young
      age, the AfSHG has developed a strong cadre of active researchers, both within
      and outside of Africa, with more than 400 members (from 16 countries across
      Africa as well as 8 other countries), and has held six successful meetings, five
      in Africa and one in the United States.

PMID- 20682861
TI  - Comparing the effectiveness of malaria vector-control interventions through a
      mathematical model.
AB  - Although some malaria-control programs are beginning to combine insecticide
      treated nets (ITNs) and indoor residual spraying (IRS), little is known about the
      effectiveness of such combinations. We use a mathematical model to compare the
      effectiveness of ITNs and IRS with dichlorodiphenyltrichloroethane (DDT) or
      bendiocarb, applied singly and in combination, in an epidemiological setting
      based in Namawala, Tanzania, with Anopheles gambiae as the primary vector. Our
      model indicates that although both IRS (with DDT) and ITNs provide personal
      protection, humans with only ITNs are better protected than those with only IRS,
      and suggests that high coverage of IRS with bendiocarb may interrupt
      transmission, as can simultaneous high coverage of ITNs and IRS with DDT. When
      adding a second vector-control intervention, it is more effective to cover the
      unprotected population first. Although our model includes some assumptions and
      approximations that remain to be addressed, these findings should be useful for
      prioritizing and designing future field research.

PMID- 20682862
TI  - Salivary polytene chromosome map of Anopheles darlingi, the main vector of
      neotropical malaria.
AB  - New photomap of Anopheles (Nyssorhynchus) darlingi Root, 1926, is described for a
      population from Guajara-Mirim, State of Rondonia, Brazil. The number of sections
      in the previous A. darlingi reference map was maintained and new subsections were
      added to the five chromosome arms. Breakage points of paracentric inversions had
      been previously incorporated into the photomap of this species. An additional
      inversion is reported, called 3Lc, totaling 14 inversions in the A. darlingi
      chromosome arms. The proposed photomap is potentially useful for further
      evolutionary studies in addition to physical and in silico chromosome mapping
      using A. darlingi genomic and transcriptome sequences. Furthermore, in our
      attempt to compare sections of the 2R chromosome arm of A. darlingi with
      Anopheles funestus, Anopheles stephensi, and Anopheles gambiae, we found great
      differences in the arrangement of the polytene chromosome bands, which are
      consistent with the known phylogenetic divergence of these species.

PMID- 20682863
TI  - Frequency distribution of antimalarial drug resistance alleles among Plasmodium
      falciparum isolates from Gezira State, central Sudan, and Gedarif State, eastern
      Sudan.
AB  - In 2004, Sudan adopted artesunate + sulfadoxine/pyrimethamine (SP) combination as
      the first-line drug, in response to the high level of falciparum resistance to
      antimalarials. In 2007, a molecular study on antimalarial resistance linked
      genes, pfcrt, pfmdr1, pfdhfr, pfdhps, and pfATPase6, was conducted on 198
      isolates from central and eastern Sudan. We observed a high frequency of point
      mutations at almost all loci analyzed, mainly of pfcrt 76T (72.7%), pfdhfr 51I
      (75.3%), and pfdhfr 108N (72.7%) alleles. The MARK III in vitro test for
      chloroquine sensitivity in 45 P. falciparum isolates showed that 37.8% of the
      isolates were low resistant and 6.7% were fully resistant. This study represents
      the most recent molecular investigation on antimalarial resistance in this area
      after the adoption of artemisinin-based combination therapy (ACT), and underlines
      the importance of the analysis of SP resistance evolution to monitor the efficacy
      of ACT therapy in endemic areas.

PMID- 20682864
TI  - An outbreak of Plasmodium falciparum malaria in U.S. Marines deployed to Liberia.
AB  - In 2003, 44 U.S. Marines were evacuated from Liberia with either confirmed or
      presumed Plasmodium falciparum malaria. An outbreak investigation showed that
      only 19 (45%) used insect repellent, 5 (12%) used permethrin-treated clothing,
      and none used bed netting. Adherence with weekly mefloquine (MQ) was reported by
      23 (55%). However, only 4 (10%) had serum MQ levels high enough to correlate with
      protection (> 794 ng/mL), and 9 (22%) had evidence of steady-state kinetics (MQ
      carboxy metabolite/MQ > 3.79). Tablets collected from Marines met USP identity
      and dissolution specifications for MQ. Testing failed to identify P. falciparum
      isolates with MQ resistance. This outbreak resulted from under use of personal
      protective measures and inadequate adherence with chemophrophylaxis. It is
      essential that all international travelers make malaria prevention measures a
      priority, especially when embarking to regions of the world with high
      transmission intensity such as west Africa..

PMID- 20682865
TI  - Indoor use of plastic sheeting impregnated with carbamate combined with long
      lasting insecticidal mosquito nets for the control of pyrethroid-resistant
      malaria vectors.
AB  - The combined efficacy of a long-lasting insecticidal net (LLIN) and a carbamate
      treated plastic sheeting (CTPS) or indoor residual spraying (IRS) for control of
      insecticide-resistant mosquitoes was evaluated in experimental huts in Burkina
      Faso. Anopheles gambiae from the area is resistant to pyrethroids and to a lesser
      extent, carbamates. Relatively low mortality rates were observed with the LLIN
      (44%), IRS (42%), and CTPS (52%), whereas both combinations killed significantly
      more mosquitoes (~70% for LLIN + CTPS and LLIN + IRS). Blood feeding by An.
      gambiae was uninhibited by IRS and CTPS compared with LLIN (43%), LLIN + CTPS
      (58%), and LLIN + IRS (56%). No evidence for selection of the kdr and ace-1(R)
      alleles was observed with the combinations, whereas a survival advantage of
      mosquitoes bearing the ace-1(R) mutation was observed with IRS and CTPS. The
      results suggest that the combination of the two interventions constitutes a
      potential tool for vector-resistance management.

PMID- 20682866
TI  - Severe rhabdomyolysis caused by Plasmodium vivax malaria in the Brazilian Amazon.
AB  - Severe rhabdomyolysis (creatine phosphokinase = 29,400 U/L) developed in a 16
      year-old boy from Manaus, Brazil, after he started treatment with chloroquine for
      infection with Plasmodium vivax. Treatment led to myoglobinuria and acute renal
      failure. After hemodialysis, the patient improved and a muscle biopsy specimen
      showed no myophosphorylase or deaminase deficiency. This case of rhabdomyolysis
      associated with P. vivax infection showed no comorbidities. The pathogenesis is
      still unclear. Although rhabdomyolysis is generally reported as a complication of
      Plasmodium falciparum malaria, leading to metabolic and renal complications,1 it
      has been reported in a patient with P. vivax infection with myoadenylate
      deaminase deficiency.2 We report a case in a patient without typical muscle
      enzyme deficiencies in which severe rhabdomyolysis developed while the patients
      was being treated with chloroquine for a confirmed P. vivax infection.

PMID- 20682867
TI  - Combined intravenous treatment with artesunate and quinine for severe malaria in
      Italy.
AB  - Severe imported malaria is an important problem in European countries, where
      approximately 8,000 cases of Plasmodium falciparum malaria are reported each
      year. Although the World Health Organization recommends intravenous artesunate
      (IVA) as the treatment of choice for severe malaria in areas of low transmission,
      it is rarely used in Europe, because it is not yet available as a drug
      manufactured under Good Manufacturing Practices. We report a series of eight
      imported severe falciparum malaria cases treated with IVA combined with
      intravenous quinine (IVQ). This combined therapy was found to be efficacious,
      safe, and well-tolerated. The only observed death occurred in a young man who
      presented 10 days after the onset of symptoms. IVA plus IVQ treatment seems to be
      an acceptable approach, because the legal risks in using an unlicensed drug for
      treating a severe malaria case denies the patient the possibility of being
      treated with the most effective regimen.

PMID- 20682868
TI  - Pyrethroid resistance in Aedes aegypti from Grand Cayman.
AB  - The Grand Cayman population of Aedes aegypti is highly resistant to DDT and
      pyrethroid insecticides. Glutathione transferase, cytochrome P450, and esterase
      levels were increased in the Grand Cayman population relative to a susceptible
      laboratory strain, but synergist studies did not implicate elevated insecticide
      detoxification as a major cause of resistance. The role of target site resistance
      was therefore investigated. Two substitutions in the voltage-gated sodium channel
      were identified, V1016I in domain II, segment 6 (IIS6) (allele frequency = 0.79)
      and F1534C in IIIS6 (allele frequency = 0.68). The role of the F1534C mutation in
      conferring resistance to insecticides has not been previously established and so
      a tetraplex polymerase chain reaction assay was designed and used to genotype
      mosquitoes that had been exposed to insecticides. The F1534C mutation was
      strongly correlated with resistance to DDT and permethrin.

PMID- 20682869
TI  - Development of a multiplexed polymerase chain reaction-restriction fragment
      length polymorphism (PCR-RFLP) assay to identify common members of the Subgenera
      Culex (Culex) and Culex (Phenacomyia) in Guatemala.
AB  - Morphological differentiation of mosquitoes in the subgenera Culex (Culex) and
      Culex (Phenacomyia) in Guatemala is difficult, with reliable identification
      ensured only through examination of larval skins from individually reared
      specimens and associated male genitalia. We developed a multiplexed polymerase
      chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay to
      identify common Cx. (Cux.) and Cx. (Phc.). Culex (Cux.) chidesteri, Cx. (Cux.)
      coronator, Cx. (Cux.) interrogator, Cx. (Cux.) quinquefasciatus, Cx. (Cux.)
      nigripalpus/Cx. (Cux.) thriambus, and Cx. (Phc.) lactator were identified
      directly with a multiplexed primer cocktail comprising a conserved forward primer
      and specific reverse primers targeting ribosomal DNA (rDNA). Culex nigripalpus
      and Cx. thriambus were differentiated by restriction digest of homologous
      amplicons. The assay was developed and optimized using well-characterized
      specimens from Guatemala and the United States and field tested with unknown
      material from Guatemala. This assay will be a valuable tool for mosquito
      identification in entomological and arbovirus ecology studies in Guatemala.

PMID- 20682870
TI  - Diarrheagenic Escherichia coli in children from Costa Rica.
AB  - More than 5,000 diarrheal cases per year receive medical care at the National
      Children's Hospital of Costa Rica, and nearly 5% of them require hospitalization.
      A total of 173 Escherichia coli strains isolated from children with diarrhea were
      characterized at the molecular, serologic, and phenotypic level. Multiplex and
      duplex polymerase chain reactions were used to detect the six categories of
      diarrheagenic E. coli. Thirty percent (n = 52) of the strains were positive,
      indicating a high prevalence among the pediatric population. Enteropathogenic E.
      coli and enteroinvasive E. coli pathotypes were the most prevalent (21% and 19%,
      respectively). Pathogenic strains were distributed among the four E. coli
      phylogenetic groups A, B1, B2, and D, with groups A and B1 the most commonly
      found. This study used molecular typing to evaluate the prevalence of
      diarrheagenic E. coli reported in Costa Rica and demonstrated the importance of
      these pathotypes in the pediatric population.

PMID- 20682871
TI  - Molecular evidence of Bartonella infection in domestic dogs from Algeria, North
      Africa, by polymerase chain reaction (PCR).
AB  - Bartonella species are being recognized as important bacterial human and canine
      pathogens, and are associated with multiple arthropod vectors. Bartonella DNA
      extracted from blood samples was obtained from domestic dogs in Algiers, Algeria.
      Polymerase chain reaction (PCR) and DNA sequence analyses of the ftsZ gene and
      the 16S-23S intergenic spacer region (ITS) were performed. Three Bartonella
      species: Bartonella vinsonii subsp. berkhoffii, Bartonella clarridgeiae, and
      Bartonells elizabethae were detected infecting Algerian dogs. To our knowledge,
      this study is the first report of detection by PCR amplification of Bartonella in
      dogs in North Africa.

PMID- 20682872
TI  - Antibiotic use in Thailand: quantifying impact on blood culture yield and
      estimates of pneumococcal bacteremia incidence.
AB  - No studies have quantified the impact of pre-culture antibiotic use on the
      recovery of individual blood-borne pathogens or on population-level incidence
      estimates for Streptococcus pneumoniae. We conducted bloodstream infection
      surveillance in Thailand during November 2005-June 2008. Pre-culture antibiotic
      use was assessed by reported use and by serum antimicrobial activity. Of 35,639
      patient blood cultures, 27% had reported pre-culture antibiotic use and 24% (of
      24,538 tested) had serum antimicrobial activity. Pathogen isolation was half as
      common in patients with versus without antibiotic use; S. pneumoniae isolation
      was 4- to 9-fold less common (0.09% versus 0.37% by reported antibiotic use;
      0.05% versus 0.45% by serum antimicrobial activity, P < 0.01). Pre-culture
      antibiotic use by serum antimicrobial activity reduced pneumococcal bacteremia
      incidence by 32% overall and 39% in children < 5 years of age. Our findings
      highlight the limitations of culture-based detection methods to estimate invasive
      pneumococcal disease incidence in settings where pre-culture antibiotic use is
      common.

PMID- 20682873
TI  - Severe multifocal form of buruli ulcer after streptomycin and rifampin treatment:
      comments on possible dissemination mechanisms.
AB  - Buruli ulcer (BU), a disease caused by Mycobacterium ulcerans, leads to the
      destruction of skin and sometimes bone. Here, we report a case of severe
      multifocal BU with osteomyelitis in a 6-year-old human immunodeficiency virus
      (HIV)-negative boy. Such disseminated forms are poorly documented and generally
      occur in patients with HIV co-infection. The advent of antibiotic treatment with
      streptomycin (S) and rifampin (R) raised hope that these multifocal BU cases
      could be reduced. The present case raises two relevant points about multifocal
      BU: the mechanism of dissemination that leads to the development of multiple foci
      and the difficulties of treatment of multifocal forms of BU. Biochemical
      (hypoproteinemia), hematological (anemia), clinical (traditional treatment), and
      genetic factors are discussed as possible risk factors for dissemination.

PMID- 20682874
TI  - ELISA versus conventional methods of diagnosing endemic brucellosis.
AB  - The diagnostic value of enzyme-linked immunosorbent assay (ELISA) was evaluated
      when blood specimens of 92 patients suspected of brucellosis underwent the ELISA
      (IgM and IgG), standard tube agglutination (SAT), and 2-mercaptoethanol (2-ME)
      tests and blood cultures; 38 sera from non-brucellosis patients and 34 sera from
      blood donors were also subjected to ELISA, SAT, and 2-ME tests. SAT was able to
      pinpoint only 23 (25%), whereas ELISA confirmed the etiology in 56 (60.9%; P <
      0.001) patients with brucellosis, including 31 culture-confirmed cases. The
      sensitivity and specificity of ELISA were 100% and 71.31%, respectively. Because
      they were confirmed by ELISA, the diagnosis could never be excluded with SAT in
      33 cases. ELISA has been found to be more sensitive in acute (28% higher
      sensitivity; P < 0.02) and chronic (55% higher sensitivity; P < 0.01) cases. For
      accurate diagnosis in suspected brucellosis cases detection, we recommend both
      ELISA IgM and IgG tests. ELISA IgG and 2-ME tests seem to be promising tools in
      judging prognosis.

PMID- 20682875
TI  - Tuberculin skin-test reactions are unaffected by the severity of hyperendemic
      intestinal helminth infections and co-infections.
AB  - The tuberculin skin test (TST) quantifies cell-mediated immunity to tuberculosis
      antigens. Helminths suppress cell-mediated immunity, so we studied the effect of
      helminth infection and deworming on the TST in a randomized, double-blind,
      placebo-controlled study in an indigenous Amazon community (N = 195). Stool
      microscopy diagnosed helminths in 98% and co-infection with multiple species in
      24% of study subjects. The TST was positive (> or = 10 mm) for 49%, and responses
      increased with age (P < 0.001), Bacille Calmette Guerin (BCG) vaccination (P =
      0.01), and tuberculosis contact (P = 0.05). TST results had no association with
      helminth-egg concentrations, species, or co-infections (all P > 0.1). One month
      after deworming with albendazole (three daily 400-mg doses), helminths were
      reduced, but 63% remained infected with helminths. Albendazole did not cause a
      change in TST size (P = 0.8) or positivity (P = 0.9) relative to placebo. Thus,
      TST reactions were unaffected by albendazole therapy that partially cured
      intestinal helminth infections, and TST interpretation was unaffected by high
      burden helminth infections and co-infection with multiple helminth species.

PMID- 20682876
TI  - Differences in clinical manifestations of imported versus autochthonous
      leptospirosis in Austria and Germany.
AB  - Leptospirosis, a zoonosis occurring worldwide, has a broad spectrum of clinical
      manifestations. Recently, various countries observed an increase of severe
      anicteric cases. In Austria and Germany, growing numbers of imported cases are
      notified in addition to autochthonous infections. The aim of this study was to
      assess whether imported and autochthonous cases differ in clinical manifestations
      and outcome. We retrospectively analyzed 24 imported and 35 autochthonous cases
      treated in six infectious disease units between 1998 and 2008. To compare disease
      severity, patients were classified according to established independent risk
      factors for fatal outcome. Although severe leptospirosis (i.e., presence of > or
      = 1 independent risk factors for death) occurred in similar proportions of
      imported (67%) and autochthonous (86%) infections (P = 0.1), imported cases were
      significantly fewer icteric (13% versus 69%; P < 0.0001). In conclusion, an
      increasing incidence of severe anicteric imported cases of leptospirosis should
      be anticipated with rising global travel activities.

PMID- 20682877
TI  - Preliminary characterization of Mus musculus-derived pathogenic strains of
      Leptospira borgpetersenii serogroup Ballum in a hamster model.
AB  - Human and animal leptospirosis caused by Leptospira spp. belonging to serogroup
      Ballum has increased worldwide in the past decade. We report the isolation and
      serologic and molecular characterization of four L. borgpetersenii serogroup
      Ballum isolates obtained from Mus musculus, and preliminary virulence studies.
      These isolates are useful for diagnosis of leptospirosis and for epidemiologic
      studies of its virulence and pathogenic mechanisms.

PMID- 20682878
TI  - Multiple zoonotic pathogens identified in canine feces collected from a remote
      Canadian indigenous community.
AB  - Five genera of potentially zoonotic bacteria and parasites were detected in
      environmentally collected fecal samples from a remote indigenous community in
      Northern Saskatchewan, Canada. Organisms identified include Toxocara canis,
      Echniococcus granulosus, Giardia duodenalis, Cryptosporidium spp., and
      Campylobacter spp. The prevalence and intensity of Giardia spp. and Campylobacter
      spp. in fecal samples was particularly remarkable. Three-quarters of samples
      tested contained at least one zoonotic species of Campylobacter, and C. jejuni
      containing feces had an average of 2.9 x 10(5) organisms/g. Over one-half of
      samples tested contained Giardia spp. with an average of 9,266 cysts/g. Zoonotic
      G. duodenalis Assemblage A was the only Giardia spp. genotype identified. These
      data suggest that canine feces have the potential to pose a significant health
      risk to Canadians in rural and remote indigenous communities.

PMID- 20682879
TI  - Zoonotic anatrichosomiasis in an Illinois resident.
AB  - We describe a case of zoonotic anatrichosomiasis in a patient from Illinois. A 44
      year-old immigrant from Mexico originally presented with a history of multiple
      oral ulcers and two submucosal nodules on the dorsal surface of the tongue. An
      incisional biopsy was taken to assist with diagnosis. Examination of stained
      sections revealed the presence of a coiled nematode. The histologic examination
      displayed trichuroid features. Anatomic structures that aided in the
      identification included esophagus embedded in a prominent stichosome in the
      anterior end, paired bacillary bands, and small size. The location of the worm
      within the oral mucosal epithelium also facilitated the diagnosis.

PMID- 20682880
TI  - Clinical and demographic stratification of test performance: a pooled analysis of
      five laboratory diagnostic methods for American cutaneous leishmaniasis.
AB  - We evaluated performance characteristics of five diagnostic methods for cutaneous
      leishmaniasis. Patients who came to the Leishmania Clinic of Hospital Nacional
      Cayetano Heredia in Lima, Peru, were enrolled in the study. Lesion smears,
      culture, microculture, polymerase chain reaction (PCR), and leishmanin skin test
      (LST) were performed. A total of 145 patients with 202 lesions were enrolled: 114
      patients with 161 lesions fulfilled criteria for cutaneous leishmaniasis.
      Sensitivity and specificity were 57.8% (95% confidence interval [CI] = 50.2
      65.4%) and 100.0% for culture, 78.3% (95% CI = 71.9-84.7%) and 100.0% for
      microculture, 71.4% (95% CI = 64.4-78.4%) and 100.0% for smears, 78.2% (95% CI =
      70.6-85.8%) and 77.4% (95% CI = 62.7-92.1%) for LST, and 96.9% (95% CI = 94.2
      99.6%) and 65.9% (95% CI = 51.4-80.4%) for PCR. PCR was more sensitive than the
      other assays (P < 0.001). Sensitivities of culture, smears, and LST varied by
      lesion duration and appearance. PCR offers performance advantages over other
      assays, irrespective of patient age, sex, lesion duration, or appearance. That
      clinical factors influence performance of non-molecular assays offers clinicians
      a patient-focused approach to diagnostic test selection.

PMID- 20682881
TI  - Efficacy of miltefosine for the treatment of American cutaneous leishmaniasis.
AB  - Miltefosine is an oral agent used for cutaneous leishmaniasis treatment. An open
      label, randomized, phase III clinical trial was carried out in the Colombian army
      population. Miltefosine, 50 mg capsule was taken orally three times per day for
      28 days (N = 145) or meglumine antimoniate, 20 mg/kg body weight per day for 20
      days by intramuscular injection (N = 143). The efficacy of miltefosine by
      protocol was 69.8% (85/122 patients) and 58.6% (85/145 patients) by intention to
      treat. For meglumine antimoniate, the efficacy by protocol was 85.1% (103/121
      patients) and 72% (103/143 patients) by intention to treat. No association was
      found between drug efficacy and L. (V.) braziliensis or L. (V.) panamensis
      species of Leishmania responsible for infection. Adverse gastrointestinal events
      were associated with the use of miltefosine, the meglumine antimoniate treatment
      was associated with adverse effects on the skeletal musculature, fever, cephalea,
      and higher toxicity in kidney, liver, pancreas, and hematological system.

PMID- 20682882
TI  - Effectiveness and safety of liposomal amphotericin B for visceral leishmaniasis
      under routine program conditions in Bihar, India.
AB  - We evaluated, through the prospective monitoring of 251 patients at Sadar
      Hospital in Bihar, India, the effectiveness and safety of 20 mg/kg body weight of
      liposomal amphotericin B for the treatment of visceral leishmaniasis. The
      treatment success rates for the intention-to-treat, per protocol, and intention
      to-treat worse-case scenario analyses were 98.8%, 99.6%, and 81.3%, respectively.
      Nearly one-half of patients experienced mild adverse events, but only 1%
      developed serious but non-life-threatening lips swelling. The lost to follow-up
      rate was 17.5%. Our findings indicate that the 20 mg/kg body weight treatment
      dosage is effective and safe under routine program conditions. Given that the
      exorbitant cost of liposomal amphotericin B is a barrier to its widespread use,
      we recommend further study to monitor and evaluate a lowered dosage and a shorter
      treatment course.

PMID- 20682883
TI  - Accuracy of rapid IgM-based immunochromatographic and immunoblot assays for
      diagnosis of acute scrub typhus and murine typhus infections in Laos.
AB  - We studied the diagnostic accuracy of a rapid immunochromatographic test (ICT)
      for detection of IgM against scrub typhus (ST ICT) and an immunoblot test for the
      detection of IgM against murine typhus (MT IBT) by using admission serum samples
      from 1,030 febrile patients in Laos. Sensitivity and specificity for the ST ICT
      determined by using the diagnostic criteria of a four-fold increase in IgM
      against Orientia tsutsugamushi between paired samples were 23.8% (95% confidence
      interval [CI] = 15.9-33.3%) and 86.2% (95% CI = 84.1-88.6%), respectively.
      Sensitivity and specificity for the ST ICT determined by using an admission IgM
      titer > or = 1:400 were 39.1% (95% CI = 34.1-44.2%) and 99.5% (95% CI = 98.7
      99.9%), respectively. Sensitivity and specificity for the MT IBT determined by
      using the criteria of a four-fold increase in IgM against Rickettsia typhi
      between paired serum samples were 61.2% (95% CI = 53.7-68.3%) and 86.5% (95% CI =
      84.1-88.8%), respectively. Sensitivity and specificity for the MT IBT determined
      by using an admission IgM titer > or = 1:400 were 54.6% (95% CI = 49.1-60.0%) and
      94.1% (95% CI = 92.0-95.7%), respectively. Both assays had relatively good
      specificity but low sensitivity and thus have limited utility for admission
      diagnosis.

PMID- 20682884
TI  - Does water hyacinth on East African lakes promote cholera outbreaks?
AB  - Cholera outbreaks continue to occur regularly in Africa. Cholera has been
      associated with proximity to lakes in East Africa, and Vibrio cholerae has been
      found experimentally to concentrate on the floating aquatic plant, water
      hyacinth, which is periodically widespread in East African lakes since the late
      1980s. From 1994 to 2008, Nyanza Province, which is the Kenyan province bordering
      Lake Victoria, accounted for a larger proportion of cholera cases than expected
      by its population size (38.7% of cholera cases versus 15.3% of national
      population). Yearly water-hyacinth coverage on the Kenyan section of Lake
      Victoria was positively associated with the number of cholera cases reported in
      Nyanza Province (r = 0.83; P = 0.0010). Water hyacinth on freshwater lakes might
      play a role in initiating cholera outbreaks and causing sporadic disease in East
      Africa.

PMID- 20682885
TI  - Diagnostic accuracy and feasibility of serological tests on filter paper samples
      for outbreak detection of T.b. gambiense human African trypanosomiasis.
AB  - Control of human African trypanosomiasis (HAT) in the Democratic Republic of
      Congo is based on mass population screening by mobile teams; a costly and labor
      intensive approach. We hypothesized that blood samples collected on filter paper
      by village health workers and processed in a central laboratory might be a cost
      effective alternative. We estimated sensitivity and specificity of micro-card
      agglutination test for trypanosomiasis (micro-CATT) and enzyme-linked
      immunosorbent assay (ELISA)/T.b. gambiense on filter paper samples compared with
      parasitology-based case classification and used the results in a Monte Carlo
      simulation of a lot quality assurance sampling (LQAS) approach. Micro-CATT and
      ELISA/T.b. gambiense showed acceptable sensitivity (92.7% [95% CI 87.4-98.0%] and
      82.2% [95% CI 75.3-90.4%]) and very high specificity (99.4% [95% CI 99.0-99.9%]
      and 99.8% [95% CI 99.5-100%]), respectively. Conditional on high sample size per
      lot (> or = 60%), both tests could reliably distinguish a 2% from a zero
      prevalence at village level. Alternatively, these tests could be used to identify
      individual HAT suspects for subsequent confirmation.

PMID- 20682886
TI  - Temporal fluctuation of infection with different Trypanosoma cruzi genotypes in
      the wild rodent Octodon degus.
AB  - We identified and followed-up for two years Octodon degus rodents infected with
      Trypanosoma cruzi genotypes by using xenodiagnosis with two vector species
      (Mepraia spinolai and Triatoma infestans), polymerase chain reaction DNA-based
      detection of insect dejections, Southern blot analysis, and minicircle
      hybridization with genotype-specific probes. Results show temporal fluctuations
      of infection with four parasite lineages (TCI, TCII, TCV, and TCVI) in one co
      infected O. degus. Results are discussed in the context of parasitemia level and
      infection control in mammal hosts.

PMID- 20682887
TI  - Community participation and domiciliary occurrence of infected Meccus longipennis
      in two Mexican villages in Jalisco state.
AB  - The entomological features of Chagas disease in two western Mexican villages were
      analyzed through triatomines collection by the inhabitants and active research in
      the peridomicile. The inhabitant collections have the following comparable
      characteristics: 1) Meccus longipennis was the dominant species (> 91%), 2)
      around 43% of the insects were collected indoors, 3) about 70% of triatomines
      were adults, 4) cumulated rates of infestation of the dwellings reached 40-50%,
      5) the triatomine infection rate by Trypanosoma cruzi was > 50%, and 6) the
      indoor triatomines frequently feed on humans (range 38.5-56.2%). However, the
      collection was twice as abundant in the first village and the peridomicile
      infestation, evaluated by the active collection, reached up to 60% and only 4.9%
      in the other village. Furthermore, females predominated in the first village,
      whereas males in the other. The current results allow discussing the course of
      action to prevent Chagas disease in this region.

PMID- 20682888
TI  - Acute arboviral infections in Guinea, West Africa, 2006.
AB  - Acute febrile illnesses comprise the majority of the human disease burden in sub
      Saharan Africa. We hypothesized that arboviruses comprised a considerable
      proportion of undiagnosed febrile illnesses in Guinea and sought to determine the
      frequency of arboviral disease in two hospitals there. Using a standard case
      definition, 47 suspected cases were detected in approximately 4 months.
      Immunoglobulin M antibody capture enzyme-linked immunosorbent assays and plaque
      reduction neutralization assays revealed that 63% (30/47) of patients were
      infected with arboviruses, including 11 West Nile, 2 yellow fever, 1 dengue, 8
      chikungunya, and 5 Tahyna infections. Except for yellow fever, these are the
      first reported cases of human disease from these viruses in Guinea and the first
      reported cases of symptomatic Tahyna infection in Africa. These results strongly
      suggest that arboviruses circulate and are common causes of disease in Guinea.
      Improving surveillance and laboratory capacity for arbovirus diagnoses will be
      integral to understanding the burden posed by these agents in the region.

PMID- 20682889
TI  - Vector-host interactions in avian nests: do mosquitoes prefer nestlings over
      adults?
AB  - The hypothesis that nestlings are a significant driver of arbovirus transmission
      and amplification is based upon findings that suggest nestlings are highly
      susceptible to being fed upon by vector mosquitoes and to viral infection and
      replication. Several previous studies have suggested that nestlings are
      preferentially fed upon relative to adults in the nest, and other studies have
      reported a preference for adults over nestlings. We directly tested the feeding
      preference of nestling and adult birds in a natural setting, introducing
      mosquitoes into nesting boxes containing eastern bluebirds (Sialia sialis),
      collecting blood-fed mosquitoes, and matching the source of mosquito blood meals
      to individual birds using microsatellite markers. Neither nestlings nor adults
      were fed upon to an extent significantly greater than would be predicted based
      upon their relative abundance in the nests, although feeding upon mothers
      decreased as the age of the nestlings increased.

PMID- 20682890
TI  - West Nile virus emergence and persistence in Los Angeles, California, 2003-2008.
AB  - West Nile virus (WNV) invaded Los Angeles in September 2003, and during the
      subsequent five-year period followed a pattern of amplification, subsidence, and
      resurgence. Enzootic transmission was tracked by abundance and infection
      incidence in Culex pipiens quinquefasciatus and Cx. tarsalis and by
      seroprevalence in peridomestic passerine birds, infection in dead birds, and
      seroconversions in sentinel chickens. Culex p. quinquefasciatus served as the
      primary vector of WNV, with gravid traps serving as the best sampling method and
      the most consistent indicator of viral activity. Spatial scan statistics applied
      to mosquito infection and positive dead bird data delimited three major clusters
      of WNV transmission, with introduction occurring in the Los Angeles Basin, and
      amplification and dispersal events carrying transmission to the San Fernando and
      Santa Clarita valleys. Los Angeles experienced major epidemics in 2004 and 2008,
      providing a unique opportunity to investigate specific patterns of enzootic
      amplification preceding epidemics.

PMID- 20682891
TI  - Infection with versus exposure to Taenia solium: what do serological test results
      tell us?
AB  - Taenia solium cysticercosis is an endemic zoonosis in many developing countries.
      Serological tests are the most appropriate diagnostic tools to understand the
      transmission dynamics of the parasite, but the performances of these methods in
      such a setting are not known. A south Ecuadorian human population living in an
      endemic area was tested using three common serological tests. Because none of
      them is a gold standard, a Bayesian Latent Class analysis was used to estimate
      the test characteristics. Two definitions of a case were considered to
      differentiate between prevalence of current infection and prior exposure to the
      parasite. Differences between the performances of the same test in function of
      the definition of a case were observed. This study shows that test results and
      prior information should be interpreted carefully in a Bayesian analysis
      framework, particularly when the latter is based on clinical studies.

PMID- 20682892
TI  - Reduction in hookworm infection after praziquantel treatment among children and
      young adults in Leyte, the Philippines.
AB  - One small previous study found that praziquantel reduced hookworm infection. In
      this study, 607 subjects were enrolled in a longitudinal study. At enrollment and
      every 3 months for 18 months, three stool samples were collected, and the
      intensity of infection with Schistosoma japonicum and soil-transmitted helminths
      (STHs) was quantified. All subjects were treated with 60 mg/kg praziquantel at
      baseline. Three months post-treatment, the percent of subjects who were hookworm
      infected decreased to 46.5% from 61% at baseline. The putative cure rate was
      23.7%. The 95% confidence interval around the change in hookworm egg counts from
      baseline to 6 and 12 months post-treatment was negative and did not include zero.
      The percent reduction in hookworm egg counts from baseline to 3 months post
      treatment was 40.8%. Praziquantel treatment did not decrease the infection
      intensity of STHs. Control programs using praziquantel may have the added benefit
      of reducing hookworm infection and anemia in areas of coendemnicity.

PMID- 20682893
TI  - Strongyloidiasis-related deaths in the United States, 1991-2006.
AB  - The objective of this study was to 1) assess the incidence of strongyloidiasis in
      the United States, 2) evaluate demographic and regional associations, and 3)
      identify comorbid conditions as risk factors for death. A population-based case
      control study was performed by using mortality data during 1991-2006. We
      identified 347 strongyloidiasis deaths (0.79 per 10 million deaths, 14-29 deaths
      per year), which decreased slightly over time. Deaths occurred primarily among
      older (median age = 66.0 years), white (57.6%) and Hispanic (22.2%) men (69.2%),
      residing in the Southeastern United States (49.3%). Associated health conditions
      included chronic obstructive pulmonary disease (28.7%, odds ratio [OR] = 4.0, 95%
      confidence interval [CI] = 3.0-5.4) and infection with human immunodeficiency
      virus (12.5%, OR = 4.6, 95% CI = 2.7-7.9). Strongyloidiasis deaths in the second
      half of the study period (1999-2006) were less likely to be associated with
      chronic obstructive pulmonary disease (19.4%, OR = 1.2, 95% CI = 0.7-1.9), but
      continued to be associated with human immunodeficiency virus infection (12.9%, OR
      = 2.8, 95% CI = 1.3-6.0). Early detection and treatment of at-risk patients with
      latent strongyloidiasis infections is needed to reduce strongyloidiasis
      mortality.

PMID- 20682894
TI  - Detection of Schistosoma mansoni and Schistosoma haematobium DNA by loop-mediated
      isothermal amplification: identification of infected snails from early
      prepatency.
AB  - Monitoring post-control transmission of schistosomes by examining humans becomes
      less effective as infection rates among humans decrease. Molecular monitoring of
      prepatent schistosome infection in snails by the polymerase chain reaction (PCR)
      has been used for studying human-to-snail transmission, and snail prepatent
      infection rates were found to correspond to infection prevalence and average
      intensity in human populations contacting the sites studied. We have now
      developed loop-mediated isothermal amplification (LAMP) assays for identifying
      Schistosoma mansoni and S. haematobium to facilitate large-scale evaluation of
      post-intervention transmission potential. LAMP primers were designed based on the
      Sm1-7 and DraI repeated sequences of the corresponding schistosomes, and
      amplification by LAMP of these 121-basepair highly abundant sequences provided a
      detection sensitivity of 0.1 fg of genomic DNA. When these LAMP assays were
      applied for examining infected laboratory snails, it was possible to identify
      infection from the first day after exposure to miracidia. The potential
      advantages of these assays are discussed.

PMID- 20682895
TI  - Prevalence and risk factors for hepatitis C virus infection among young Thai men.
AB  - Epidemiologic studies of hepatitis C virus (HCV) infection are unusual in
      developing countries, especially Thailand. We evaluated the prevalence and risk
      factors for HCV among military conscripts, including a sample of 5,246 men (1:30
      sample), and human immunodeficiency virus (HIV)-1 positive men (N = 500) between
      2005 and 2008. The HCV prevalence was 2.2% in the sampled group and 8.4% in HIV-1
      sero-positives. Among the sampled group, HIV-1 infection, injection drug use
      (IDU) history, and unsafe injections were associated with HCV infection; adjusted
      prevalence rate ratios [RRs; 95% confidence intervals (CIs)] were 3.7 (1.04
      12.77), 1.9 (1.04-3.54), and 1.8 (1.02-3.11), respectively. Among HIV-1 sero
      positives, an IDU history and residence in southern Thailand were associated with
      HCV prevalence; adjusted RRs (95% CIs) were 3.5 (1.71-7.24) and 2.6 (1.18-5.61),
      respectively. Public health measures to prevent HCV in Thailand should focus on
      reducing injection drug use and other exposures to unsafe injections among young
      Thai men.

PMID- 20682897
TI  - Response to Hossain and others: hospital-based surveillance for Japanese
      encephalitis at four sites in Bangladesh, 2003-2005.

PMID- 20682896
TI  - Multiple outbreaks of puffer fish intoxication in Bangladesh, 2008.
AB  - During April and June 2008, we investigated three outbreaks of marine puffer fish
      intoxication in three districts of Bangladesh (Narshingdi, Natore, and Dhaka). We
      also explored trade of marine puffer fish in Cox's Bazaar, a coastal area of the
      country. We identified 95 people who had consumed puffer fish; 63 (66%) developed
      toxicity characterized by tingling sensation in the body, perioral numbness,
      dizziness, and weakness, 14 of them died. All three outbreaks were caused by
      consumption of large (0.2-1.5 kg) marine puffer fish, sold in communities where
      people were unfamiliar with the marine variety of the fish and its toxicity.
      Coastal fishermen reported that some local businessmen distributed the fresh fish
      to non-coastal parts of the country, where people were unfamiliar with the larger
      variety, to make a quick profit. Lack of knowledge about marine puffer toxicity
      contributed to the outbreaks. Health communication campaigns will enhance
      people's knowledge and may prevent future outbreaks.

PMID- 20682899
TI  - Rift Valley Fever: scientific pathways toward public health prevention and
      response.

PMID- 20682900
TI  - An investigation of a major outbreak of Rift Valley fever in Kenya: 2006-2007.
AB  - An outbreak of Rift Valley fever (RVF) occurred in Kenya during November 2006
      through March 2007. We characterized the magnitude of the outbreak through
      disease surveillance and serosurveys, and investigated contributing factors to
      enhance strategies for forecasting to prevent or minimize the impact of future
      outbreaks. Of 700 suspected cases, 392 met probable or confirmed case
      definitions; demographic data were available for 340 (87%), including 90 (26.4%)
      deaths. Male cases were more likely to die than females, Case Fatality Rate Ratio
      1.8 (95% Confidence Interval [CI] 1.3-3.8). Serosurveys suggested an attack rate
      up to 13% of residents in heavily affected areas. Genetic sequencing showed high
      homology among viruses from this and earlier RVF outbreaks. Case areas were more
      likely than non-case areas to have soil types that retain surface moisture. The
      outbreak had a devastatingly high case-fatality rate for hospitalized patients.
      However, there were up to 180,000 infected mildly ill or asymptomatic people
      within highly affected areas. Soil type data may add specificity to climate-based
      forecasting models for RVF.

PMID- 20682901
TI  - Risk factors for severe Rift Valley fever infection in Kenya, 2007.
AB  - A large Rift Valley fever (RVF) outbreak occurred in Kenya from December 2006 to
      March 2007. We conducted a study to define risk factors associated with infection
      and severe disease. A total of 861 individuals from 424 households were enrolled.
      Two hundred and two participants (23%) had serologic evidence of acute RVF
      infection. Of these, 52 (26%) had severe RVF disease characterized by hemorrhagic
      manifestations or death. Independent risk factors for acute RVF infection were
      consuming or handling products from sick animals (odds ratio [OR] = 2.53, 95%
      confidence interval [CI] = 1.78-3.61, population attributable risk percentage
      [PAR%] = 19%) and being a herds person (OR 1.77, 95% CI = 1.20-2.63, PAR% = 11%).
      Touching an aborted animal fetus was associated with severe RVF disease (OR =
      3.83, 95% CI = 1.68-9.07, PAR% = 14%). Consuming or handling products from sick
      animals was associated with death (OR = 3.67, 95% CI = 1.07-12.64, PAR% = 47%).
      Exposures related to animal contact were associated with acute RVF infection,
      whereas exposures to mosquitoes were not independent risk factors.

PMID- 20682902
TI  - Epidemiologic and clinical aspects of a Rift Valley fever outbreak in humans in
      Tanzania, 2007.
AB  - In January 2007, an outbreak of Rift Valley fever (RVF) was detected among humans
      in northern Tanzania districts. By the end of the outbreak in June, 2007, 511
      suspect RVF cases had been recorded from 10 of the 21 regions of Tanzania, with
      laboratory confirmation of 186 cases and another 123 probable cases. All
      confirmed RVF cases were located in the north-central and southern regions of the
      country, with an eventual fatality rate of 28.2% (N = 144). All suspected cases
      had fever; 89% had encephalopathy, 10% hemorrhage, and 3% retinopathy. A total of
      169 (55%) of the 309 confirmed or probable cases were also positive for malaria
      as detected by peripheral blood smear. In a cohort of 20 RVF cases with known
      outcome that were also positive for human immunodeficiency virus, 15 (75%) died.
      Contact with sick animals and animal products, including blood, meat, and milk,
      were identified as major risk factors of acquiring RVF.

PMID- 20682903
TI  - Rift Valley fever virus epidemic in Kenya, 2006/2007: the entomologic
      investigations.
AB  - In December 2006, Rift Valley fever (RVF) was diagnosed in humans in Garissa
      Hospital, Kenya and an outbreak reported affecting 11 districts. Entomologic
      surveillance was performed in four districts to determine the epidemic/epizootic
      vectors of RVF virus (RVFV). Approximately 297,000 mosquitoes were collected,
      164,626 identified to species, 72,058 sorted into 3,003 pools and tested for RVFV
      by reverse transcription-polymerase chain reaction. Seventy-seven pools
      representing 10 species tested positive for RVFV, including Aedes
      mcintoshi/circumluteolus (26 pools), Aedes ochraceus (23 pools), Mansonia
      uniformis (15 pools); Culex poicilipes, Culex bitaeniorhynchus (3 pools each);
      Anopheles squamosus, Mansonia africana (2 pools each); Culex quinquefasciatus,
      Culex univittatus, Aedes pembaensis (1 pool each). Positive Ae. pembaensis, Cx.
      univittatus, and Cx. bitaeniorhynchus was a first time observation. Species
      composition, densities, and infection varied among districts supporting
      hypothesis that different mosquito species serve as epizootic/epidemic vectors of
      RVFV in diverse ecologies, creating a complex epidemiologic pattern in East
      Africa.

PMID- 20682904
TI  - Pathologic studies on suspect animal and human cases of Rift Valley fever from an
      outbreak in Eastern Africa, 2006-2007.
AB  - Rift Valley fever (RVF) is an important viral zoonotic disease in Africa with
      periodic outbreaks associated with severe disease, death, and economic hardship.
      During the 2006-2007 outbreaks in Eastern Africa, postmortem and necropsy tissue
      samples from 14 animals and 20 humans clinically suspected of RVF were studied
      with histopathologic evaluation and immunohistochemical (IHC) assays. Six animal
      and 11 human samples had IHC evidence of Rift Valley fever virus (RVFV) antigens.
      We found that extensive hepatocellular necrosis without prominent inflammatory
      cell infiltrates is the most distinctive histopathologic change in liver tissues
      infected with RVFV. Pathologic studies on postmortem tissue samples can help
      establish the diagnosis of RVF, differentiating from endemic diseases with
      clinical manifestations similar to RVF, such as malaria, leptospirosis, or yellow
      fever.

PMID- 20682905
TI  - Prediction, assessment of the Rift Valley fever activity in East and Southern
      Africa 2006-2008 and possible vector control strategies.
AB  - Historical outbreaks of Rift Valley fever (RVF) since the early 1950s have been
      associated with cyclical patterns of the El Nino/Southern Oscillation (ENSO)
      phenomenon, which results in elevated and widespread rainfall over the RVF
      endemic areas of Africa. Using satellite measurements of global and regional
      elevated sea surface temperatures, elevated rainfall, and satellite derived
      normalized difference vegetation index data, we predicted with lead times of 2-4
      months areas where outbreaks of RVF in humans and animals were expected and
      occurred in the Horn of Africa, Sudan, and Southern Africa at different time
      periods from September 2006 to March 2008. Predictions were confirmed by
      entomological field investigations of virus activity and by reported cases of RVF
      in human and livestock populations. This represents the first series of
      prospective predictions of RVF outbreaks and provides a baseline for improved
      early warning, control, response planning, and mitigation into the future.

PMID- 20682906
TI  - An assessment of the regional and national socio-economic impacts of the 2007
      Rift Valley fever outbreak in Kenya.
AB  - Although Rift Valley fever (RVF) has significant impacts on human health and
      livestock production, it can also induce significant (and often overlooked)
      economic losses among various stakeholders in the marketing chain. This work
      assesses and quantifies the multi-dimensional socio-economic impacts of the 2007
      RVF outbreak in Kenya based on a rapid assessment of livestock value chains in
      the northeast part of the country and a national macroeconomic analysis. Although
      study results show negative impacts among producers in terms of food insecurity
      and reductions in income, we also found significant losses among other downstream
      actors in the value chain, including livestock traders, slaughterhouses, casual
      laborers, and butchers, as well as other, non-agricultural sectors. The study
      highlights the need for greater sensitivity and analyses that address the
      multitude of economic losses resulting from an animal disease to better inform
      policy and decision making during animal health emergencies.

PMID- 20682907
TI  - Rift Valley fever outbreak in livestock in Kenya, 2006-2007.
AB  - We analyzed the extent of livestock involvement in the latest Rift Valley fever
      (RVF) outbreak in Kenya that started in December 2006 and continued until June
      2007. When compared with previous RVF outbreaks in the country, the 2006-07
      outbreak was the most extensive in cattle, sheep, goats, and camels affecting
      thousands of animals in 29 of 69 administrative districts across six of the eight
      provinces. This contrasted with the distribution of approximately 700 human RVF
      cases in the country, where over 85% of these cases were located in four
      districts; Garissa and Ijara districts in Northeastern Province, Baringo district
      in Rift Valley Province, and Kilifi district in Coast Province. Analysis of
      livestock and human data suggests that livestock infections occur before virus
      detection in humans, as supported by clustering of human RVF cases around
      livestock cases in Baringo district. The highest livestock morbidity and
      mortality rates were recorded in Garissa and Baringo districts, the same
      districts that recorded a high number of human cases. The districts that reported
      RVF in livestock for the first time in 2006/07 included Kitui, Tharaka, Meru
      South, Meru central, Mwingi, Embu, and Mbeere in Eastern Province, Malindi and
      Taita taveta in Coast Province, Kirinyaga and Murang'a in Central Province, and
      Baringo and Samburu in Rift Valley Province, indicating that the disease was
      occurring in new regions in the country.

PMID- 20682908
TI  - Epidemiological assessment of the Rift Valley fever outbreak in Kenya and
      Tanzania in 2006 and 2007.
AB  - To capture lessons from the 2007 Rift Valley fever (RVF) outbreak,
      epidemiological studies were carried out in Kenya and Tanzania. Somali
      pastoralists proved to be adept at recognizing symptoms of RVF and risk factors
      such as heavy rainfall and mosquito swarms. Sandik, which means "bloody nose,"
      was used by Somalis to denote disease consistent with RVF. Somalis reported that
      sandik was previously seen in 1997/98, the period of the last RVF epidemic.
      Pastoralists communicated valuable epidemiological information for surveillance
      and early warning systems that was observed before international warnings. The
      results indicate that an all or none approach to decision making contributed to
      the delay in response. In the future, a phased approach balancing actions against
      increasing risk of an outbreak would be more effective. Given the time required
      to mobilize large vaccine stocks, emergency vaccination did not contribute to the
      mitigation of explosive outbreaks of RVF.

PMID- 20682909
TI  - The historical and recent impact of Rift Valley fever in Africa.

PMID- 20682910
TI  - Decision-support tool for prevention and control of Rift Valley fever epizootics
      in the Greater Horn of Africa.
AB  - In East Africa, Rift Valley fever (RVF) usually occurs as explosive epizootics
      with prolonged inter-epidemic periods on the order of 8 to 10 years. The episodic
      nature of the disease and the rapid evolution of outbreaks create special
      challenges for its mitigation and control. Following the events of the 2006 and
      2007 RVF outbreak in East Africa, decision-makers assembled their collective
      experiences in the form of a risk-based decision support tool to help guide
      responses in future emergencies. The premise of the tool is that a series of
      natural events are indicative of the increasing risk of an outbreak and that
      actions should be matched to this evolving risk profile. In this manner,
      investment in prevention and control can be qualitatively optimized. The decision
      support tool is a living document written through stakeholder input. This
      publication captures the current tool as an example of risk-based decision
      support.

PMID- 20682912
TI  - HCMV-encoded chemokine receptor US28 mediates proliferative signaling through the
      IL-6-STAT3 axis.
AB  - US28 is a viral G protein (heterotrimeric guanosine triphosphate-binding protein)
      coupled receptor encoded by the human cytomegalovirus (HCMV). In addition to
      binding and internalizing chemokines, US28 constitutively activates signaling
      pathways linked to cell proliferation. Here, we show increased concentrations of
      vascular endothelial growth factor and interleukin-6 (IL-6) in supernatants of
      US28-expressing NIH 3T3 cells. Increased IL-6 was associated with increased
      activation of the signal transducer and activator of transcription 3 (STAT3)
      through upstream activation of the Janus-activated kinase JAK1. We used
      conditioned growth medium, IL-6-neutralizing antibodies, an inhibitor of the IL-6
      receptor, and short hairpin RNA targeting IL-6 to show that US28 activates the IL
      6-JAK1-STAT3 signaling axis through activation of the transcription factor
      nuclear factor kappaB and the consequent production of IL-6. Treatment of cells
      with a specific inhibitor of STAT3 inhibited US28-dependent [(3)H]thymidine
      incorporation and foci formation, suggesting a key role for STAT3 in the US28
      mediated proliferative phenotype. US28 also elicited STAT3 activation and IL-6
      secretion in HCMV-infected cells. Analyses of tumor specimens from glioblastoma
      patients demonstrated colocalization of US28 and phosphorylated STAT3 in the
      vascular niche of these tumors. Moreover, increased phospho-STAT3 abundance
      correlated with poor patient outcome. We propose that US28 induces proliferation
      in HCMV-infected tumors by establishing a positive feedback loop through
      activation of the IL-6-STAT3 signaling axis.

PMID- 20682914
TI  - Light still shines in the darkness: decent care for all.
AB  - Health care is in crisis at the global, national, and local levels, with hundreds
      of millions living without basic care, or with insufficient care. Current health
      care models seem to have ignored, muted, or excluded the voices of the people
      they were intended to serve, resulting in health systems and care delivery models
      that do not respond to the needs of the people. This article describes a values
      based approach to health and health care services in which the voices of the
      people are heard and listened to, and in which individuals and communities are
      informed participants in their own care. We draw parallels between contemporary
      concerns for decency in care giving to Florence Nightingale's path-breaking work,
      first with the British military medical system and then Great Britain as a whole.

PMID- 20682913
TI  - The nonphagocytic NADPH oxidase Duox1 mediates a positive feedback loop during T
      cell receptor signaling.
AB  - Production of reactive oxygen species, often by NADPH (reduced form of
      nicotinamide adenine dinucleotide phosphate) oxidases, plays a role in the
      signaling responses of cells to many receptor stimuli. Here, we describe the
      function of the calcium-dependent, nonphagocytic NADPH oxidase Duox1 in primary
      human CD4(+) T cells and cultured T cell lines. Duox1 bound to inositol 1,4,5
      trisphosphate receptor 1 and was required for early T cell receptor (TCR)
      stimulated production of hydrogen peroxide (H(2)O(2)) through a pathway that was
      dependent on TCR-proximal kinases. Transient or stable knockdown of Duox1
      inhibited TCR signaling, especially phosphorylation of tyrosine-319 of zeta chain
      associated protein kinase of 70 kilodaltons (ZAP-70), store-operated entry of
      calcium ions (Ca(2+)), and activation of extracellular signal-regulated kinase.
      The production of cytokines was also inhibited by knockdown of Duox1. Duox1
      mediated inactivation of Src homology 2 domain-containing protein tyrosine
      phosphatase 2 promoted the phosphorylation of ZAP-70 and its association with the
      Src family tyrosine kinase Lck and the CD3zeta chain of the TCR complex. Thus, we
      suggest that activation of Duox1, downstream of proximal TCR signals, generates
      H(2)O(2) that acts in a positive feedback loop to enhance and sustain further TCR
      signaling.

PMID- 20682915
TI  - Self-transcendence and spiritual well-being in the Amish.
AB  - Self-transcendence, the ability to expand one's relationship to others and the
      environment, has been found to provide hope which helps a person adapt and cope
      with illness. Spiritual well-being, the perception of health and wholeness, can
      boost self-confidence and self esteem. The purpose of this descriptive
      correlational study was to describe the relationship between self-transcendence
      and spiritual well-being in adult Amish. A random sample of Old Order Amish was
      surveyed by postal mail; there were 134 respondents. Two valid and reliable
      questionnaires were used to measure the key variables. The participants had high
      levels of self-transcendence and spiritual well-being and there was a
      statistically significant positive relationship between the two variables. The
      findings from this study will increase nurses' awareness of the holistic nature
      of the Amish beliefs and assist nurses in serving this population. Additional
      research is needed to develop further understanding of the study variables among
      the Amish.

PMID- 20682916
TI  - A history of massage in nurse training school curricula (1860-1945).
AB  - INTRODUCTION: Guided by Florence Nightingale, massage nurse training instruction
      methods were duplicated in the U.S. nurse training curricula. In the 1880s to
      1900s massage training and instruction was delivered by physicians, nurses, or
      masseurs for many disease conditions. In the 1930s to 1940s, influential nurse
      authors and educators began to recommend specialization in physiotherapy for
      nurses. Scientific and pharmacological solutions for symptoms of disease became
      popular, thus practicing basic nursing comfort measures using massage declined.
      PURPOSES: To trace roots of massage in the medical literature, the inclusion of
      massage in U.S. nurse training school curricula, and examine the historical shift
      from massage as a basic nursing comfort measure to a specialization of
      physiotherapy. METHOD: Primary text books by physicians, nurses, massage
      instructors; medical/nursing journals; nursing curriculum guidelines--archival
      collections of the Center for Historical Nursing Inquiry; Historical Collections
      at the University of Virginia Claude Moore Health Sciences Library; private
      historical collections; and secondary published books/ articles were used.
      FINDINGS: Prior to increase in scientific care, use of analgesics, and
      specialization of physiotherapy departments, the nurse provided basic comfort
      measures that included massage. Historical research in the use of massage in
      nursing may help refocus attention on the healing of the mind/body and reinforce
      the value of compassionate touch and balance in nursing practice today.

PMID- 20682917
TI  - Interhospital transfers among Medicare beneficiaries admitted for acute
      myocardial infarction at nonrevascularization hospitals.
AB  - BACKGROUND: Patients with acute myocardial infarction (AMI) who are admitted to
      hospitals without coronary revascularization are frequently transferred to
      hospitals with this capability, yet we know little about the basis for how such
      revascularization hospitals are selected. METHODS AND RESULTS: We examined
      interhospital transfer patterns in 71 336 AMI patients admitted to hospitals
      without revascularization capabilities in the 2006 Medicare claims using network
      analysis and regression models. A total of 31 607 (44.3%) AMI patients were
      transferred from 1684 nonrevascularization hospitals to 1104 revascularization
      hospitals. Median time to transfer was 2 days. Median transfer distance was 26.7
      miles, with 96.1% within 100 miles. In 45.8% of cases, patients bypassed a closer
      hospital to go to a farther hospital that had a better 30-day risk standardized
      mortality rates. However, in 36.8% of cases, another revascularization hospital
      with lower 30-day risk-standardized mortality was actually closer to the original
      admitting nonrevascularization hospital than the observed transfer destination.
      Adjusted regression models demonstrated that shorter transfer distances were more
      common than transfers to the hospitals with lowest 30-day mortality rates.
      Simulations suggest that an optimized system that prioritized the transfer of AMI
      patients to a nearby hospital with the lowest 30-day mortality rate might produce
      clinically meaningful reductions in mortality. CONCLUSIONS: More than 40% of AMI
      patients admitted to nonrevascularization hospitals are transferred to
      revascularization hospitals. Many patients are not directed to nearby hospitals
      with the lowest 30-day risk-standardized mortality, and this may represent an
      opportunity for improvement.

PMID- 20682918
TI  - A national cancer clinical trials system for the 21st century: reinvigorating the
      NCI Cooperative Group Program.

PMID- 20682923
TI  - The cover. The legend of John Brown.

PMID- 20682924
TI  - A piece of my mind. The haircut.

PMID- 20682925
TI  - Child marriage threatens girls' health.

PMID- 20682926
TI  - Violence in health care settings on rise.

PMID- 20682927
TI  - Antiepileptic medications and the risk of suicide.

PMID- 20682928
TI  - Antiepileptic medications and the risk of suicide.

PMID- 20682929
TI  - Insurance and financial concerns among patients seeking care for acute myocardial
      infarction.

PMID- 20682930
TI  - Donor policies for stem cell transplantation.

PMID- 20682931
TI  - Donor policies for stem cell transplantation.

PMID- 20682932
TI  - Effects of a brief intervention for reducing violence and alcohol misuse among
      adolescents: a randomized controlled trial.
AB  - CONTEXT: Emergency department (ED) visits present an opportunity to deliver brief
      interventions to reduce violence and alcohol misuse among urban adolescents at
      risk of future injury. OBJECTIVE: To determine the efficacy of brief
      interventions addressing violence and alcohol use among adolescents presenting to
      an urban ED. DESIGN, SETTING, AND PARTICIPANTS: Between September 2006 and
      September 2009, 3338 patients aged 14 to 18 years presenting to a level I ED in
      Flint, Michigan, between 12 pm and 11 pm 7 days a week completed a computerized
      survey (43.5% male; 55.9% African American). Adolescents reporting past-year
      alcohol use and aggression were enrolled in a randomized controlled trial
      (SafERteens). INTERVENTION: All patients underwent a computerized baseline
      assessment and were randomized to a control group that received a brochure (n =
      235) or a 35-minute brief intervention delivered by either a computer (n = 237)
      or therapist (n = 254) in the ED, with follow-up assessments at 3 and 6 months.
      Combining motivational interviewing with skills training, the brief intervention
      for violence and alcohol included review of goals, tailored feedback, decisional
      balance exercise, role plays, and referrals. MAIN OUTCOME MEASURES: Self-report
      measures included peer aggression and violence, violence consequences, alcohol
      use, binge drinking, and alcohol consequences. RESULTS: About 25% (n = 829) of
      screened patients had positive results for both alcohol and violence; 726 were
      randomized. Compared with controls, participants in the therapist intervention
      showed self-reported reductions in the occurrence of peer aggression (therapist, 
      34.3%; control, -16.4%; relative risk [RR], 0.74; 95% confidence interval [CI],
      0.61-0.90), experience of peer violence (therapist, -10.4%; control, +4.7%; RR,
      0.70; 95% CI, 0.52-0.95), and violence consequences (therapist, -30.4%; control, 
      13.0%; RR, 0.76; 95% CI, 0.64-0.90) at 3 months. At 6 months, participants in the
      therapist intervention showed self-reported reductions in alcohol consequences
      (therapist, -32.2%; control, -17.7%; odds ratio, 0.56; 95% CI, 0.34-0.91)
      compared with controls; participants in the computer intervention also showed
      self-reported reductions in alcohol consequences (computer, -29.1%; control, 
      17.7%; odds ratio, 0.57; 95% CI, 0.34-0.95). CONCLUSION: Among adolescents
      identified in the ED with self-reported alcohol use and aggression, a brief
      intervention resulted in a decrease in the prevalence of self-reported aggression
      and alcohol consequences. TRIAL REGISTRATION: clinicaltrials.gov Identifier:
      NCT00251212.

PMID- 20682933
TI  - Effect of an advocacy intervention on mental health in Chinese women survivors of
      intimate partner violence: a randomized controlled trial.
AB  - CONTEXT: Intimate partner violence (IPV) against women can have negative mental
      health consequences for survivors; however, the effect of interventions designed
      to improve survivors' depressive symptoms is unclear. OBJECTIVE: To determine
      whether an advocacy intervention would improve the depressive symptoms of Chinese
      women survivors of IPV. DESIGN, SETTING, AND PARTICIPANTS: Assessor-blinded
      randomized controlled trial of 200 Chinese women 18 years or older with a history
      of IPV, conducted from February 2007 to June 2009 in a community center in Hong
      Kong, China. INTERVENTION: The intervention group (n = 100) received a 12-week
      advocacy intervention comprising empowerment and telephone social support. The
      control group (n = 100) received usual community services including child care,
      health care and promotion, and recreational programs. MAIN OUTCOME MEASURES:
      Primary outcome was change in depressive symptoms (Chinese version of the Beck
      Depression Inventory II) between baseline and 9 months. Secondary outcomes were
      changes in IPV (Chinese Revised Conflict Tactics Scales), health-related quality
      of life (12-Item Short Form Health Survey), and perceived social support
      (Interpersonal Support Evaluation List) between baseline and 9 months. Usefulness
      of the intervention and usual community services was evaluated at 9 months.
      RESULTS: At 3 months, the mean change in depressive symptom score was 11.6 (95%
      CI, 9.5 to 13.7) in the control group and 14.9 (95% CI, 12.4 to 17.5) in the
      intervention group; respective changes at 9 months were 19.6 (95% CI, 16.6 to
      22.7) and 23.2 (95% CI, 20.4 to 26.0). Intervention effects at 3 and 9 months
      were not significantly different (P = .86). The intervention significantly
      reduced depressive symptoms by 2.66 (95% CI, 0.26 to 5.06; P = .03) vs the
      control, less than the 5-unit minimal clinically important difference.
      Statistically significant improvement was found in partner psychological
      aggression (-1.87 [95% CI, -3.34 to -0.40]; mean change at 3 months, 1.5 [95% CI,
      -1.0 to 3.9] in the control group and 0.3 [95% CI, -0.7 to 1.4] in the
      intervention group; mean change at 9 months, -6.4 [95% CI, -7.8 to -5.0] and -8.9
      [95% CI, -10.6 to -7.2]) and perceived social support (2.18 [95% CI, 0.48 to
      3.89]; mean change at 3 months, 6.4 [95% CI, 4.9 to 7.8] and 9.2 [95% CI, 7.7 to
      10.8]; mean change at 9 months, 12.4 [95% CI, 10.5 to 14.3] and 14.4 [95% CI,
      12.7 to 16.1]) but not in physical assault, sexual coercion, or health-related
      quality of life. By end of study, more women in the intervention group found the
      advocacy intervention useful or extremely useful in improving intimate
      relationships vs those in the control group receiving usual community services
      (93.8% vs 81.7%; difference, 12.1% [95% CI, 2.1% to 22.0%]; P = .02) and in
      helping them to resolve conflicts with their intimate partners (97.5% vs 84.1%;
      difference, 13.4% [95% CI, 4.7% to 22.0%]; P = .001). CONCLUSION: Among community
      dwelling abused Chinese women, an advocacy intervention did not result in a
      clinically meaningful improvement in depressive symptoms. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT01054898.

PMID- 20682934
TI  - Association of exposure to violence and potential traumatic events with self
      reported physical and mental health status in the Central African Republic.
AB  - CONTEXT: For decades, the Central African Republic (CAR) has experienced
      violence, economic stagnation, and institutional failure. The latest wave of
      violence erupted in 2001 and continues to this day in some areas. Yet there has
      been little attention to the conflict and even less research to document and
      quantify the conflict's human cost. OBJECTIVE: To study levels of violence in
      CAR, including mortality levels, and the association between exposure to violence
      and traumatic events with self-reported physical and mental health status.
      DESIGN, SETTING, AND PARTICIPANTS: Multistage stratified cluster random survey of
      1879 adults 18 years or older in selected households conducted in 5
      administrative units of CAR (3 in the south, which has been free from recent
      violence, and 2 in the north, in which violence continues) between October and
      December 2009. MAIN OUTCOME MEASURES: Mortality, morbidity, exposure to potential
      traumatic events, sense of insecurity, and meeting of symptom criteria for
      depression and anxiety using the Hopkins Symptom Checklist-25 with a cut-off
      score of 1.75. RESULTS: The crude mortality rate (CMR) was 4.9 deaths (95%
      confidence interval [CI], 4.6-5.1) per 1000 population per month and self
      reported CMR due to violence was 0.8 deaths (95% CI, 0.6-1.0) per 1000 population
      per month. Thirty-five percent reported their physical health status as being
      good or very good while 29% described it as bad or very bad. Respondents in
      northern prefectures reported higher rates of mortality, exposure to trauma, and
      insecurity and lower levels of physical health and access to health services
      compared with those in the south. The estimated prevalences of symptoms of
      depression and anxiety were 55.3% (95% CI, 51.6%-59.0%) and 52.5% (95% CI, 48.1%
      56.8%), respectively. Exposure to violence and self-reported physical health were
      statistically associated with mental health outcomes (P < .001). Anxiety symptom
      scores were higher for respondents in the northern prefectures than those in the
      south (t = 2.54, P = .01). CONCLUSION: A high proportion of adult respondents in
      CAR reported witnessing or having personally experienced traumatic events over
      the course of the conflicts, and more than half met symptom criteria for
      depression and anxiety.

PMID- 20682935
TI  - Association of sexual violence and human rights violations with physical and
      mental health in territories of the Eastern Democratic Republic of the Congo.
AB  - CONTEXT: Studies from the Eastern Region of the Democratic Republic of the Congo
      (DRC) have provided anecdotal reports of sexual violence. This study offers a
      population-based assessment of the prevalence of sexual violence and human rights
      abuses in specific territories within Eastern DRC. OBJECTIVE: To assess the
      prevalence of and correlations with sexual violence and human rights violations
      on residents of specific territories of Eastern DRC including information on
      basic needs, health care access, and physical and mental health. DESIGN, SETTING,
      AND PARTICIPANTS: A cross-sectional, population-based, cluster survey of 998
      adults aged 18 years or older using structured interviews and questionnaires,
      conducted over a 4-week period in March 2010. MAIN OUTCOME MEASURES: Sexual
      violence prevalence and characteristics, symptoms of major depressive disorder
      (MDD) and posttraumatic stress disorder (PTSD), human rights abuses, and physical
      and mental health needs among Congolese adults in specific territories of Eastern
      DRC. RESULTS: Of the 1005 households surveyed 998 households participated,
      yielding a response rate of 98.9%. Rates of reported sexual violence were 39.7%
      (95% confidence interval [CI], 32.2%-47.2%; n = 224/586) among women and 23.6%
      (95% CI, 17.3%-29.9%; n = 107/399) among men. Women reported to have perpetrated
      conflict-related sexual violence in 41.1% (95% CI, 25.6%-56.6%; n = 54/148) of
      female cases and 10.0% (95% CI, 1.5%-18.4%; n = 8/66) of male cases. Sixty-seven
      percent (95% CI, 59.0%-74.5%; n = 615/998) of households reported incidents of
      conflict-related human rights abuses. Forty-one percent (95% CI, 35.3%-45.8%; n =
      374/991) of the represented adult population met symptom criteria for MDD and
      50.1% (95% CI, 43.8%-56.3%; n = 470/989) for PTSD. CONCLUSION: Self-reported
      sexual violence and other human rights violations were prevalent in specific
      territories of Eastern DRC and were associated with physical and mental health
      outcomes.

PMID- 20682936
TI  - Violent behavior in mental illness: the role of substance abuse.

PMID- 20682937
TI  - Affect regulation and prevention of risky behaviors.

PMID- 20682938
TI  - Large-scale "expert" mortality surveys in conflicts--concerns and
      recommendations.

PMID- 20682939
TI  - Roles of CIA physicians in enhanced interrogation and torture of detainees.

PMID- 20682940
TI  - The role of paraprofessionals in providing treatment for posttraumatic stress
      disorder in low-resource communities.

PMID- 20682941
TI  - Violence, condom negotiation, and HIV/STI risk among sex workers.

PMID- 20682942
TI  - Adolescent alcohol use and violence: are brief interventions the answer?

PMID- 20682943
TI  - Intimate partner violence against women: what outcomes are meaningful?

PMID- 20682944
TI  - JAMA patient page. Intimate partner violence.

PMID- 20682945
TI  - Prevention of ischemia-reperfusion injury in mice kidneys by low-dose whole body
      irradiation preconditioning.

PMID- 20682947
TI  - Characterization of static and dynamic left ventricular diastolic function in
      patients with heart failure with a preserved ejection fraction.
AB  - BACKGROUND: Congestive heart failure in the setting of a preserved left
      ventricular (LV) ejection fraction is increasing in prevalence among the senior
      population. The underlying pathophysiologic abnormalities in ventricular function
      and structure remain unclear for this disorder. We hypothesized that patients
      with heart failure with preserved ejection fraction (HFPEF) would have marked
      abnormalities in LV diastolic function with increased static diastolic stiffness
      and slowed myocardial relaxation compared with age-matched healthy controls.
      METHODS AND RESULTS: Eleven highly screened patients (4 men, 7 women) aged 73+/-7
      years with HFPEF were recruited to participate in this study. Thirteen sedentary
      healthy controls (7 men, 6 women) aged 70+/-4 years also were recruited. All
      subjects underwent pulmonary artery catheterization with measurement of cardiac
      output, end-diastolic volumes, and pulmonary capillary wedge pressures at
      baseline; cardiac unloading (lower-body negative pressure or upright tilt); and
      cardiac loading (rapid saline infusion). The data were used to define the Frank
      Starling and LV end-diastolic pressure-volume relationships. Doppler
      echocardiographic data (tissue Doppler velocities, isovolumic relaxation time,
      propagation velocity of early mitral inflow , E/A-wave ratio) were obtained at
      each level of cardiac preload. Compared with healthy controls, patients with
      HFPEF had similar LV contractile function and static LV compliance but reduced LV
      chamber distensibility with elevated filling pressures and slower myocardial
      relaxation as assessed by tissue Doppler imaging. CONCLUSIONS: In this small,
      highly screened patient population with hemodynamically confirmed HFPEF,
      increased end-diastolic static ventricular stiffness relative to age-matched
      controls was not a universal finding. Nevertheless, patients with HFPEF, even
      when well compensated, had elevated filling pressures, reduced distensibility,
      and increased diastolic wall stress compared with controls. In contrast, LV
      relaxation as assessed by tissue Doppler variables appeared consistently impaired
      in patients with HFPEF.

PMID- 20682948
TI  - Shorter stay, longer life: age at migration and mortality among the older Mexican
      origin population.
AB  - OBJECTIVE: In this article, we investigate the association between age at
      migration and mortality during a 13-year period in a sample of Mexican American
      immigrants 65 and older at baseline. METHOD: We employ the Hispanic Established
      Populations for Epidemiologic Studies of the Elderly (H-PESE) to control for
      mortality-related health and social factors. RESULTS: Our analyses show that the
      immigrant generation does not represent a homogeneous mortality risk category.
      Individuals who migrated to the United States in mature adulthood have a
      considerably lower risk of death than individuals who migrated in childhood or
      midlife. Chronic conditions or functional capacity do not account for these
      differences. CONCLUSION: Our findings suggest that standard risk pools may differ
      significantly on the basis of genetic and unmeasured life-course factors. A
      better understanding of the late-life immigrant mortality advantage has important
      implications for more effective and targeted social and medical interventions.

PMID- 20682950
TI  - Choroidal macrovessel.

PMID- 20682949
TI  - Dynamics of family economic hardship and the progression of health problems of
      husbands and wives during the middle years: a perspective from rural Mid-West.
AB  - OBJECTIVE: The objective of this study was to investigate the influence of
      theoretically important dimensions of stability and change in economic hardship
      during early middle years on decade-long health problems of husbands and wives.
      METHOD: The study used prospective data collected from 360 middle-aged husbands
      and wives during a 12-year period. The variables included self-reported economic
      hardship (22 items), mental and physical health, and physical impairment.
      RESULTS: The results supported the hypothesis that the dynamics of family
      economic hardship (in terms of stability and change) during the early middle
      years contribute to subsequent onset of health problems of middle-aged husbands
      and wives. These health problems in turn progress as an interrelated process
      through intrahealth-domain continuities, cross-health domain proliferations, and
      dyadic associations as they pass through midlife. DISCUSSION: A better
      understanding of these processes may aid in the formation and effective
      implementation of health promotion programs for middle-aged husbands and wives.

PMID- 20682951
TI  - 'ToPDoG' is in progress.

PMID- 20682952
TI  - Clinical value of diagnostic instruments for ruling out acute coronary syndrome
      in patients with chest pain: a systematic review.
AB  - BACKGROUND: Acute chest pain is a frequent reason to attend an emergency room,
      and various instruments for calculating the probability of an acute coronary
      syndrome exist. OBJECTIVE: To assess the safety and efficiency of all available
      instruments investigated in sample validation studies. METHODS: A systematic
      review was conducted. Studies were identified describing the development of
      instruments and all subsequent validations in electronic databases and reference
      lists of included studies. Inclusion was screened for, full papers checked and
      data extracted on salient clinical features, performance characteristics and
      quality in duplicate. RESULTS: Of 20 derivation studies, 10 were at least
      validated once in 14 validations including 26,488 patients. One study by Selker
      and colleagues was validated in six new patient series and studies by Goldman et
      al and the Kennedy et al were both validated in three new patient series. All
      other studies were validated less than three times. In four out of six
      validations of the Selker et al study, the sensitivity of the prediction rule was
      98% or higher. The corresponding values for specificity ranged from 4% to 34%.
      All remaining prediction rules showed sensitivity values below 95% in all
      validations. CONCLUSIONS: No instrument assisting clinicians in the diagnostic
      investigation of patients with suspected acute coronary syndrome consistently
      fulfils the safety requirements of clinicians.

PMID- 20682953
TI  - Anxiety and depression are unrecognised in emergency patients admitted to the
      observation care unit.
AB  - OBJECTIVE: To assess the sensitivity and specificity of emergency physicians in
      detecting anxiety and depression in patients requiring admission to the emergency
      department (ED) observation care unit for complementary investigations/treatment.
      METHODS: 339 consecutive patients admitted to the emergency observation care unit
      of 14 EDs were interviewed with standardised questionnaires. The characteristics
      of the patients, EDs and attending ED physicians were collected. Patients'
      anxiety and depression were identified using the Hospital Anxiety and Depression
      Scale (HADS), a self-administered questionnaire. ED physicians were blind to the
      HADS score and were asked to declare whether they perceived anxiety and
      depression in each patient. The judgement of ED physicians and the HADS score
      were compared using sensitivity, specificity, positive and negative likelihood
      ratios. RESULTS: The HADS questionnaire was correctly completed by 310 patients
      who comprised the study population. HADS detected symptoms of anxiety in 148
      patients (47%) and symptoms of depression in 70 patients (23%). ED physicians
      determined the presence or absence of anxiety with a sensitivity of 48% (95% CI
      40% to 56%) and a specificity of 69% (95% CI 61% to 75%). Positive and negative
      likelihood ratios were 1.54 (95% CI 1.16 to 2.06) and 0.75 (95% CI 1.28 to 3.28)
      for anxiety. They detected the presence or absence of depression with a
      sensitivity of 39% (95% CI 28% to 51%) and a specificity of 78% (95% CI 72% to
      83%). Positive and negative likelihood ratios were 1.75 (95% CI 1.20 to 2.56) and
      0.78 (95% CI 1.26 to 3.87) for depression. CONCLUSION: Although patients
      presenting to the ED often experience anxiety and depression, these symptoms are
      poorly detected by ED physicians.

PMID- 20682954
TI  - Imaging findings in angiotensin-converting enzyme inhibitor induced angioedema.

PMID- 20682955
TI  - Paramedic decision making: prehospital thrombolysis and beyond.
AB  - BACKGROUND: Mortality from acute myocardial infarction is influenced by the speed
      at which reperfusion therapy is delivered. In the U.K., prehospital thrombolysis
      (PHT), administered by paramedics, has been developed to improve call to needle
      (CTN) times. Recently, it has been shown in randomised trials that mortality can
      be further reduced by primary percutaneous coronary intervention (PPCI). This
      project was developed to assess current ST-elevation myocardial infarction
      practice in a district general hospital and to prepare paramedics for PPCI.
      METHODS: Data were collected prospectively over a 12-month period for all
      patients who received thrombolysis for a presumed myocardial infarct. The primary
      outcome measures for each case were who delivered the thrombolysis, either the
      paramedic crew or the hospital, and if the patient did not receive PHT the reason
      why not. Secondary outcome measures included the CTN time. RESULTS: 153 patients
      received thrombolysis over the time period (99 men, 54 women, mean age 66 +/- 15
      years). Of this group, 55 patients received PHT (35.9%) with a median CTN time of
      36 min (inter-quartile range (IQR) 30-42 min). The commonest reason for exclusion
      from receiving PHT was that the patient's history did not fit the eligibility
      criteria (25% of cases). CONCLUSIONS: Paramedics are able to deliver PHT promptly
      and safely. With the focus now on PPCI, it is anticipated that not only will
      paramedics be able to select patients for delivery to a heart attack centre for
      PPCI, they will be selecting many more patients for this treatment than have up
      to now received PHT.

PMID- 20682956
TI  - Homelessness: patterns of emergency department use and risk factors for re
      presentation.
AB  - OBJECTIVES: To describe patterns of service use and to predict risk factors for
      re-presentation to a metropolitan emergency department (ED) among people who are
      homeless. METHODS: A retrospective cohort analysis was undertaken over a 24-month
      period from a principal referral hospital in Melbourne, Australia. All ED visits
      relating to people classified as homeless were included. A predictive model for
      risk of re-presentation was developed using logistic regression with random
      effects. Rates of re-presentation, defined as the total number of visits to the
      same ED within 28 days of discharge, were measured. RESULTS: The study period was
      1 January 2003 to 31 December 2004. The re-presentation rate for homeless people
      was 47.8% (3199/6689) of ED visits and 45.5% (725/1595) of the patients. The
      final predictive model included risk factors, which incorporated both hospital
      and community service use. Those characteristics that resulted in significantly
      increased odds of re-presentation were leaving hospital at own risk (OR 1.31; 95%
      CI 1.10 to 1.56), treatment in another hospital (OR 1.45, 95% CI 1.23 to 1.72)
      and being in receipt of community-based case management (OR 1.31, 95% CI 1.11 to
      1.54) or pension (OR 1.34, 95% CI 1.12 to 1.62). CONCLUSIONS: The predictive
      model identified nine risk factors of re-presentation to the ED for people who
      are homeless. Early identification of these factors among homeless people may
      alert clinicians to the complexity of issues influencing an individual ED visit.
      This information can be used at admission and discharge by ensuring that homeless
      people have access to services commensurate with their health needs. Improved
      linkage between community and hospital services must be underscored by the
      capacity to provide safe and secure housing.

PMID- 20682957
TI  - Aorto-iliac occlusion masquerading as a ruptured abdominal aortic aneurysm.

PMID- 20682958
TI  - Ligamentum teres sign.

PMID- 20682960
TI  - Intraocular foreign body in an F-18 jet mechanic.

PMID- 20682959
TI  - The inpatient management of syncope.
AB  - INTRODUCTION: The management and risk stratification of patients with syncope in
      the Emergency Department (ED) has been the emphasis of much recent research,
      however little is known about inpatient management especially in the UK. The aim
      of this study was to examine the inpatient management of patients with syncope
      admitted to hospital from a UK ED. METHODS: This was a single centre prospective
      observational cohort study, recruiting patients with syncope admitted to hospital
      from a UK ED. Inpatient management was examined focusing on length of stay and
      investigations undertaken. RESULTS: Between 3 March 2007 and 22 July 2008, 540
      patients presenting with syncope to the ED of the Royal Infirmary of Edinburgh,
      UK were admitted and enrolled. Median and mean length of stay was 1 day (IQR 1-4)
      and 6.3 days (SD 15.5). In all, 392 (73%) patients were admitted to General/Acute
      Medicine, 39 (7%) to Cardiology, 35 (7%) to Medicine of the Elderly, 33 (6%) to
      surgical specialities and the rest to other specialities. A diagnosis was finally
      made in 342 (63%) patients including 33 (85%) of the 39 admitted to Cardiology
      and 239 (61%) of the 392 patients admitted to General/Acute Medicine. The use of
      diagnostic tests varied between specialities with more intensive investigation
      undertaken in patients admitted to Cardiology. CONCLUSIONS: The current approach
      to the inpatient management of syncope is speciality dependent. Standardised
      diagnostic pathways may improve diagnostic yield and cost effectiveness.

PMID- 20682961
TI  - Pelvic kidney.

PMID- 20682962
TI  - Optimising care in a Swiss University Emergency Department by implementing a
      multicentre trauma register (TARN): report on evaluation, costs and benefits of
      trauma registries.
AB  - BACKGROUND: Diagnostic and therapeutic approaches to trauma patients are,
      depending on experience, equipment and different therapeutic doctrines, subject
      to wide variations. The ability to compare trauma centres using a standardised
      trauma register helps to reveal unresolved systemic issues and simplifies the
      quality management in an Emergency Department (ED). METHODS: This study describes
      the selection, implementation and initial evaluation process of an international
      trauma register in a level 1 ED in a university hospital. Furthermore, first
      preliminary results and a literature review on the benefits are presented.
      RESULTS: The UK-based Trauma and Research Network (TARN) was found to be the most
      suitable register for a level 1 Swiss trauma centre. In contrast to the majority
      of the mortality-oriented registry systems, the database is capable of predicting
      the probability of survival for the referenced patients. Staff and technical
      adaptations were arranged and regular and reliable data acquisition and entry was
      ensured within 6 weeks. The University Hospital Bern has performed well from the
      very beginning and ranks within the top ten hospitals. CONCLUSIONS: With TARN, an
      appropriate trauma register has been chosen. First preliminary results have been
      obtained, and it was concluded that there was a good match between TARN's patient
      cohort and the Bernese. On the basis of the data entered into the register, the
      hospital authorities can now plan and perform improvements on the individual
      aspects of trauma care. Due to an objective comparability, weak points can be
      identified, lessons can be learned and further improvement can be achieved.

PMID- 20682963
TI  - Articulating the role of relationships in access to home care nursing at the end
      of life.
AB  - In this article, we draw on data collected from two samples of home care nurses
      to examine how relationships between nurses and family caregivers intersected
      with access to palliative home care nursing services. Participants referred to
      relationships as important for their practical benefits and for access to care:
      good relationships enhanced the nurse's ability to assess clients and families
      and fostered the family's trust in the nurse's care. Although emphasizing the
      need to build and maintain relationships (often requiring time), participants
      simultaneously referred to beliefs about the need to control the personal
      emotions invoked in relationships so as to ensure appropriate access for clients
      and families. Future research should further explore how the organizational and
      resource context, and the culture of palliative care, shape nurses' beliefs about
      relationships in their practice, the nature and types of relationships that can
      develop, and both client and family caregivers' access to care.

PMID- 20682964
TI  - Creating bridges between researchers and long-term care homes to promote quality
      of life for residents.
AB  - Improving the quality of life for long-term care (LTC) residents is of vital
      importance. Researchers need to involve LTC staff in planning and implementing
      interventions to maximize the likelihood of success. The purposes of this study
      were to (a) identify barriers and facilitators of LTC homes' readiness to
      implement evidence-based interventions, and (b) develop strategies to facilitate
      their implementation. A mixed methods design was used, primarily driven by the
      qualitative method and supplemented by two smaller, embedded quantitative
      components. Data were collected from health care providers and administrators
      using 13 focus groups, 26 interviews, and two surveys. Findings revealed that
      participants appreciated being involved at early stages of the project, but
      receptiveness to implementing innovations was influenced by study characteristics
      and demands within their respective practice environment. Engaging staff at the
      planning stage facilitated effective communication and helped strategize
      implementation within the constraints of the system.

PMID- 20682965
TI  - Alternative view of health behavior: the experience of older Korean women.
AB  - In this study we explored the perspectives of older Korean women on the
      principles and meanings of health behavior. Participants were 12 women age 65 and
      older, with no serious illnesses requiring hospitalization, who were living
      independently. We used an interpretative phenomenological approach for data
      collection and analysis. Seven themes emerged: (a) eating well in accordance with
      one's physical requirements; (b) maintaining one's inherited health; (c)
      controlling one's illness properly; (d) maintaining good relationships with close
      relatives and friends; (e) being modest and free from greed; (f) staying in
      harmony with nature; and (g) regaining energy and vitality. These experiences
      were mainly based on the traditional Korean concept of health promotion, "food is
      medicine," rather than on Western concepts of health promotion. In providing
      optimal geriatric nursing care for Korean older women, the results will be
      significant because they are based on older women's traditional Korean
      perspectives of health promotion rather than existing perspectives of Western
      medicine.

PMID- 20682966
TI  - Perceptions of life balance among a working population in Sweden.
AB  - A life in balance is commonly related to health and well-being. However, our
      knowledge regarding the perceptions of life balance among the general population
      is limited. Our aim was to explore the perception of life balance among working
      people without recent long-term sick leave. Individual interviews were conducted
      with 7 men and 12 women and analyzed according to grounded theory, aiming at
      achieving a description. The results showed that life balance includes four
      interrelated dimensions: activity balance, balance in body and mind, balance in
      relation to others, and time balance. Life balance was regarded by the
      participants as health related, promoted by a sense of security, and affected by
      context and individual strategies. Life balance was also seen as being
      individually defined and dynamic. The results indicate that the perceptions of
      life balance might be quite general because they show similarities with previous
      research on different populations.

PMID- 20682967
TI  - Everyday nursing practice values in the NICU and their reflection on
      breastfeeding promotion.
AB  - In this ethnographic study I examined neonatal intensive care unit (NICU) nurses'
      everyday practice values and explored how breastfeeding promotion fit within this
      context. The study was conducted over a 14-month period and included participant
      observation and interviewing of 114 purposively selected nurses in a level-IV
      NICU in the United States. Uncertainty emerged as a central concern underlying
      everyday practice values. Three themes described these values: (a) maximizing
      babies' potentials in the midst of uncertainty; (b) relying on the sisterhood of
      NICU nurses to deal with uncertainty; and (c) confronting uncertainty through
      tight control of actions, reliance on technology, and maximal efficiency in use
      of time. A fourth theme demonstrated how these values were reflected in NICU
      breastfeeding practices. Although high-control, high-tech, and time-urgent
      practice values were helpful in confronting uncertainty, these values also posed
      challenges to ongoing nursing efforts to promote breastfeeding. These values must
      be addressed for effective breastfeeding promotion.

PMID- 20682968
TI  - Researching mental health in minority ethnic communities: reflections on
      recruitment.
AB  - In this article we reflect on the recruitment of research participants to two
      related studies of experiences of mental health problems in Black and minority
      ethnic communities in the United Kingdom. A total of 65 people were recruited via
      three main strategies: the employment of bicultural recruiters, intensive
      information sharing about the studies, and work through local community groups.
      Three main issues seemed to affect recruitment: gatekeepers' attitudes, the
      (non)payment of participants, and reciprocal arrangements with local community
      groups. The type of strategy employed resulted in recruits with differing
      characteristics (although our sample was too small to draw generalizable
      conclusions). We conclude that to ensure that research participation is
      accessible to all, researchers must employ flexible recruitment methods that
      permit adaptation to specific needs arising out of health status, level of
      involvement with services, culture, and socioeconomic status. Systematic research
      into this part of the research process is needed.

PMID- 20682969
TI  - Uncovering the lived experience of well-being.
AB  - The words well-being, health, and wellness are commonly used in an
      interchangeable manner by health care professionals and the lay public. We
      undertook a hermeneutic phenomenological study of well-being and discovered a
      soulful strength and a rhythmic flow to this lived experience. There is a letting
      go that is experienced as a tension and rhythmic interchange, as in breathing.
      Harmony and balance lie at its foundation. Well-being requires a personal drive
      to exist. It is not experienced through purposeful means; rather, it is
      experienced in a self-forgetful way, in the free space where life unfolds and
      where people come to see their worlds in different ways. The results of this
      research suggest the experience of well-being holds a significant place within
      nursing practice for clients and for nurses.

PMID- 20682971
TI  - Care in the context of the complexity of psoriasis.
AB  - Previous research has demonstrated the multidimensional challenges of living with
      psoriasis and dermatology wards provide a unique setting in which to reach people
      strongly affected by this disease. The aim of this study is to determine the
      components of care that psoriasis patients and dermatology nurses consider to be
      important during hospitalization. A purposeful sample of seven psoriasis
      inpatients and seven dermatology nurses were interviewed in depth during a 3
      month period in 2006-2007. The data are analyzed with a modified version of
      Giorgi's phenomenological method. Patients consider hospitalization a relief from
      everyday life with psoriasis and describe its treatment as the focus of nursing
      care. Despite their knowledge of the psychosocial aspects of psoriasis, nurses
      consider the physical manifestations of the disease most important. The patients'
      descriptions of the challenges in their everyday lives illustrate an area of
      concern among psoriasis inpatients that is not actively addressed by nursing
      care.

PMID- 20682972
TI  - RB stabilizes XPC and promotes cellular NER.
AB  - It has long been thought that the G(1)/S cell cycle checkpoint allows time for
      DNA repair by delaying S-phase entry. The p53 tumor suppressor pathway regulates
      the G(1)/S checkpoint by regulating the cyclin-dependent kinase inhibitor
      p21(Waf1/Cip1), but p53 also regulates the nucleotide excision DNA repair protein
      XPC. Here, using p53-null cell lines we show that additional mechanisms stabilize
      XPC protein and promote nucleotide excision repair (NER) in concert with the
      G(1)/S checkpoint. At least one mechanism to stabilize and destabilize XPC
      involves ubiquitin-mediated degradation of XPC, as the ubiquitin ligase inhibitor
      MG-132 blocked XPC degradation. The retinoblastoma protein RB, in its
      unphosphorylated form actually stabilized XPC and promoted NER as measured by
      host cell reactivation experiments. The data suggest that XPC protein and XPC
      mediated NER are tightly linked to the G(1)/S checkpoint, even in cells lacking
      functional p53.

PMID- 20682973
TI  - Aberrant promoter hypermethylation and genomic hypomethylation in tumor, adjacent
      normal tissues and blood from breast cancer patients.
AB  - BACKGROUND: Promoter hypermethylation and global hypomethylation in the human
      genome are hallmarks of most cancers. Detection of aberrant methylation in white
      blood cells (WBC) has been suggested as a marker for cancer development, but has
      not been extensively investigated. This study was carried out to determine
      whether aberrant methylation in WBC DNA can be used as a surrogate biomarker for
      breast cancer risk. PATIENTS AND METHODS: Promoter hypermethylation of 8 tumor
      suppressor genes (RASSF1A, APC, HIN1, BRCA1, CYCLIND2, RARbeta, CDH1 and TWIST1)
      and DNA methylation for three repetitive elements (LINE1, Sat2 and Alu) were
      analyzed in invasive ductal carcinoma of the breast, paired adjacent normal
      tissue and WBC from 40 breast cancer patients by the MethyLight assay.
      Methylation in WBC from 40 controls was also analyzed. RESULTS: Tumor and
      adjacent tissues showed frequent hypermethylation for all genes tested, while WBC
      DNA was rarely hypermethylated. For HIN1, RASSF1A, APC and TWIST1, there was
      agreement between hypermethylation in tumor and adjacent tissues (p=0.04, p=0.02,
      p=0.005 and p<0.0001, respectively). DNA methylation for the three repetitive
      elements was lower in tumor compared to adjacent tissue and WBC DNA. Significant
      correlations in the methylation of Sat2M1 between tumor and adjacent tissues and
      WBC DNA were found (p<0.0001 and p=0.046, respectively). There was also a
      significant difference in methylation of Sat2M1 between cases and controls
      (p=0.01). CONCLUSION: These results suggest that further studies of WBC
      methylation, including prospective studies, may provide biomarkers of breast
      cancer risk.

PMID- 20682974
TI  - (-)-Epigallocatechin-3-gallate (EGCG) post-transcriptionally and post
      translationally suppresses the cell proliferative protein TROP2 in human
      colorectal cancer cells.
AB  - BACKGROUND: TROP-2 is a tumor-promoting molecule that has been found to be
      overexpressed in many cancer cells, making it a plausible biomarker of
      carcinogenesis. The main aim of this study was to examine the effect of green tea
      catechins (namely, (-)-epigallocatechin-3-gallate; EGCG) on TROP-2 expression.
      MATERIALS AND METHODS: Western blot and RT-PCR were applied to assess TROP2
      expression in colorectal cancer cells and tissues. RESULTS: Two different
      mechanisms were found to operate in diverse cell lines. In SW480 cells, EGCG
      affected the post-transcriptional processing of the TROP-2 mRNA, as this was
      quickly and specifically degraded in the presence of EGCG. In HCT-116 cells, EGCG
      affected TROP-2 expression at the post-translational level. TROP-2 was found to
      be highly expressed in colorectal tumors compared to adjacent normal tissues.
      CONCLUSION: This study provided a novel beneficial activity of green tea as an
      anti-tumorigenagent causing the suppression of TROP-2 in colorectal cancer.

PMID- 20682975
TI  - Anticancer activity of novel unnatural synthetic isoprenoids.
AB  - BACKGROUND: The KRAS oncogene has a high prevalence in solid malignancies.
      Targeting KRAS and inappropriate activation of the MAPK pathway with novel drugs
      is of interest. This study developed and screened a library of compounds designed
      to inhibit KRAS signaling by altering prenyl function. MATERIALS AND METHODS: To
      screen a library of novel farnesyl analogs for their anticancer activity in human
      lung cancer and breast cancer cell lines. To evaluate if the designed and actual
      pharmacology are congruent. RESULTS: Sixty-seven novel compounds were tested and
      70% of them screened positive for activity in at least one cell line. Two active
      compounds inhibited phosphorylation of MAP kinase consistent with KRAS
      inhibition. CONCLUSION: Although 47 of the 67 novel agents screened positive for
      activity, none of them were highly potent. However, targeting RAS with compounds
      that compete with farnesyl and geranylgeranyl modification of the protein remains
      viable and further work is already underway to create second generation
      molecules.

PMID- 20682976
TI  - Epithelial-mesenchymal transition in EGFR-TKI acquired resistant lung
      adenocarcinoma.
AB  - BACKGROUND: The epithelial to mesenchymal transition (EMT) may well play a part
      in determining the sensitivity to epidermal growth factor receptor (EGFR)
      tyrosine kinase inhibitor (TKI). However to date, no study has investigated the
      association between the EMT status and acquired resistance using cancer
      specimens. PATIENTS AND METHODS: Immunohistochemical (IHC) staining was used to
      analyse the protein expression of epithelial and mesenchymal markers in tumour
      samples from lung adenocarcinoma patients. Mutations in the EGFR and K-ras gene
      were also examined. RESULTS: All patients showed a positive expression of
      epithelial markers in sensitive tumours. Tumour in 4 (44.4%) out of 9 patients
      showed down-regulation of epithelial markers or up-regulation of mesenchymal
      markers. The change in the EMT status between pre-and post-treatment was shown in
      2 cases each with and without the T790M mutation. CONCLUSION: EMT plays a role in
      approximately half of the cases of resistance to EGFR-TKI, independent of T790M
      mutation.

PMID- 20682977
TI  - Epigallocatechin-3-gallate, a natural polyphenol, inhibits cell proliferation and
      induces apoptosis in human ovarian cancer cells.
AB  - BACKGROUND: Epigallocatechin-3-gallate (EGCG) is a polyphenol constituent present
      in green tea previously shown to inhibit cancer growth. However, studies on human
      ovarian cancer are limited. This study evaluated, the effects of EGCG as a
      potential anti-proliferative and pro-apoptotic agent in the human ovarian cancer
      line, SKOV-3. MATERIALS AND METHODS: The MTS assay which measures metabolic
      activity of cells, bromodeoxyuridine (BrdU) incorporation assay, and flow
      cytometry were used for the cell proliferation studies and cell morphology, DNA
      fragmentation analysis and the TUNEL assay for apoptotic effects. RESULTS: The
      EGCG treated SKOV-3 cells showed inhibition of cell viability and proliferation
      in a dose-dependent manner. Furthermore, EGCG-mediated SKOV-3 cell growth
      inhibition was associated with apoptotic changes as evident by cell cycle arrest
      and accumulation of cells in the apoptotic phase, cell morphological changes, DNA
      fragmentation and TUNEL-positive apoptotic cells. CONCLUSION: In SKOV-3 cells,
      EGCG inhibits cell proliferation via DNA synthesis reduction and induces
      apoptotic cell death via DNA damage, thus elucidating a novel, plausible
      mechanism of EGCG anti-tumorigenic property.

PMID- 20682978
TI  - Expression and localization of e-cadherin in epithelial ovarian cancer.
AB  - BACKGROUND: Findings for the role of E-cadherin in ovarian cancer (OC) are
      controversial. The aim of this study was to analyze the expression and prognostic
      role of E-cadherin in OC. MATERIALS AND METHODS: Expression analysis of E
      cadherin was performed by immunohistochemistry in 36 patients (12 primary OC, 15
      recurrent OC, 9 benign ovarian lesions). Tumor specimens were collected within
      OC. Correlation analysis with clinicopathological factors and survival was
      performed. RESULTS: E-Cadherin was significantly reduced in OC compared to benign
      ovarian lesions (p=0.024). In primary OC, E-cadherin was comparable in ovarian
      tumor and corresponding metastatic tumor tissue. E-Cadherin showed no association
      with clinicopathological factors. A significant correlation between increased
      volume of ascites and higher E-cadherin immunoexpression was found in primary OC
      (p=0.029). E-Cadherin expression showed no statistically prognostic significance
      for survival (p=0.856). CONCLUSION: The function of E-cadherin in OC remains
      controversial and needs to be elucidated further in larger studies.

PMID- 20682979
TI  - Oxaliplatin resistance induced by ERCC1 up-regulation is abrogated by siRNA
      mediated gene silencing in human colorectal cancer cells.
AB  - BACKGROUND: Oxaliplatin is used to treat patients with colorectal cancer (CRC);
      however, half the patients fail to benefit. The excision repair cross
      complementing group-1 (ERCC1) gene was studied and it was hypothesized that its
      inducible expression contributes to cellular resistance. MATERIALS AND METHODS:
      Thirty CRC cell lines were treated with oxaliplatin and sensitivity was
      determined by apoptosis. Four sensitive and resistant cell lines were analyzed
      for oxaliplatin effect on ERCC1 expression and two resistant cell lines were
      subjected to siRNA-mediated gene silencing. RESULTS: There was no correlation of
      basal ERCC1 mRNA expression with response to oxaliplatin. ERCC1 mRNA was induced
      at 24, 48, and 72 hours (71-264%, p<0.05) and ERCC1 protein at 48 hours (123
      521%, p<0.05) post-oxaliplatin treatment in resistant cells only. siRNA-mediated
      silencing of ERCC1 sensitized the CRC cells to oxaliplatin-induced apoptosis, and
      increased cleaved PARP. CONCLUSION: ERCC1 gene expression is inducible,
      contributes to oxaliplatin resistance, and is reversible by targeted suppression
      of ERCC1, identifying ERCC1 as a potential target for drug development.

PMID- 20682980
TI  - Heat-shock protein 27 is phosphorylated in gemcitabine-resistant pancreatic
      cancer cells.
AB  - BACKGROUND: Gemcitabine (2'-deoxy-2'-difluorodeoxycytidine: Gemzar) (GEM) appears
      to be the only effective anticancer drug for pancreatic cancer, but it has little
      impact on outcome due to a high level of inherent and acquired tumor resistance.
      Our previous proteomic study demonstrated that the expression of three spots of
      heat-shock protein 27 (HSP27) was increased in GEM-resistant pancreatic cancer
      cells and could play a role in determining the sensitivity of pancreatic cancer
      to GEM. MATERIALS AND METHODS AND RESULTS: In the present study, using one
      dimensional and two-dimensional Western blotting, we elucidated that these three
      spots of HSP27 were phosphorylated in GEM-resistant pancreatic cancer cell line,
      KLM1-R. CONCLUSION: Phosphorylated HSP27 may play an important role in the
      resistance to GEM, and it could also be a possible biomarker for predicting the
      response of pancreatic cancer patients to treatment with GEM.

PMID- 20682981
TI  - Tumor cure probability during alpha-RIT of ovarian cancer with different
      radiation sensitivity.
AB  - PURPOSE: To calculate the tumor cure probability (TCP) and metastatic cure
      probability (MCP) during alpha-radioimmunotherapy (alpha-RIT) of small ovarian
      cancer tumors with cells of different radiation sensitivity. MATERIALS AND
      METHODS: An in-house-developed biokinetic model and a Monte-Carlo program were
      used to calculate the cumulative activity on tumor cell surfaces and the specific
      energy to tumor cell nuclei, respectively. An in-house-developed computational
      model was used to calculate the TCP and MCP as a function of assumed radiation
      sensitivities, expressed as D(37), of the tumor cells. The calculations were
      performed using various assumptions regarding the activity distribution in
      measured tumors and used the alpha-particle energies emitted from astatine-211
      ((211)At). Regarding the calculations of the cumulative activity on each cell
      surface, the number of antigenic sites expressed by NIH:OVCAR-3 cells for the mAb
      MX35 F(ab')2 was used. To illustrate the tumor growth at the peritoneum in nude
      mice, scanning electron microscopy images were used. RESULTS: In the case of a
      maximum diffusion depth of 30 mum for the activity in the tumors, the TCP was
      high for D(37) values not exceeding approximately 4.3, approximately 2.9,
      approximately 1.8, and approximately 0.8 Gy for 200, 100, 50, and 25 kBq (211)At
      MX35 F(ab')2 four weeks after cell inoculation, respectively. In order to achieve
      complete remission of the metastatic disease in mice (i.e. MCP=1), the D(37)
      value should not exceed approximately 2.2, approximately 1.3, approximately 0.6,
      and approximately 0.3 Gy when injecting 200, 100, 50, or 25 kBq, respectively,
      assuming a maximum diffusion depth of 30 mum for the activity in the tumors.
      CONCLUSION: The radiation sensitivity, expressed as D(37), of tumor cells
      subjected to alpha-RIT could be decisive for therapeutic outcome, expressed as
      TCP or MCP, when treating small tumors of ovarian cancer.

PMID- 20682982
TI  - Iodination increases the activity of verapamil derivatives in reversing PGP
      multidrug resistance.
AB  - Iodinated derivatives of verapamil were synthesized and tested as P-glycoprotein
      (Pgp)-mediated multidrug resistance (MDR) reversal agents. The ability of these
      compounds to revert MDR was evaluated on daunorubicin-resistant K562 cells, by
      measuring the intracellular accumulation of rhodamine 123, a fluorescent probe of
      Pgp transport activity. One of the investigated compounds (16c) was found to be a
      more potent MDR reversal agent than verapamil and cyclosporin A, used as
      reference molecules. Further in vitro studies showed that compound 16c restored
      daunorubicin activity and, when used alone, did not induce cell death, cell cycle
      perturbation and modification of calcium channel activity in comparison with
      verapamil.

PMID- 20682983
TI  - MGMT activity in mucosal epithelium and squamous cell carcinoma of the head and
      neck.
AB  - Smoking and alcohol abuse cause squamous cell carcinoma of the head and neck
      (SCCHN) through smoke-induced mutations, which are counteracted by O(6)
      methylguanine-DNA methyltransferase (MGMT). This study aimed at elucidating the
      role of MGMT in SCCHN and its precursor lesions (SIN). MGMT was also determined
      in the normal mucosa (NM) and blood lymphocytes (PBLCs). RESULTS: a) MGMT was
      lower in NM than in PBLCs. b) Smoking reduced MGMT in NM but had no effect in
      PBLCs. c) MGMT activity increased in the sequence NM<SIN II and III<CIS. d) There
      was no correlation between MGMT and prognostic parameters or clinical course in
      SCCHN. The data suggest that MGMT becomes down-regulated due to smoking in non
      cancerous pharyngeal mucosa. The low MGMT activity in early dysplastic mucosal
      lesions may increase the risk for tumour development. Since some advanced
      carcinomas showed low MGMT activity, chemotherapy with O(6)-alkylating agents
      might be an alternative option.

PMID- 20682984
TI  - DNA microarray analysis of signaling pathway in macrophages stimulated by lignin
      carbohydrate complex from lentinus edodes mycelia (LEM) extract.
AB  - In order to investigate the action point of lignin-carbohydrate complex (Fr4)
      from Lentinus edodes mycelia extract, DNA microarray analysis was performed,
      using mouse macrophage-like J774.1 cells. Among seven lignin-carbohydrate complex
      fractions, Fr4 showed the highest stimulatory activity of tumor necrosis factor
      production by mouse macrophage-like J774.1 cells, as well as its previously
      reported anti-HIV activity. Fr4 is composed of lignin precursors such as vanillic
      acid, syringic acid, p-coumaric acid and ferulic acid, with trace amounts of
      flavonoids and tannins, and negligible amount of lipopolysaccharides (LPS),
      confirming the authenticity of Fr4 as a lignin. DNA microarray analysis suggested
      that Fr4 may affect immune response-related gene expression; however, it may not
      affect the expression of as many genes as LPS does.

PMID- 20682985
TI  - Knock-down of superoxide dismutase 1 sensitizes cisplatin-resistant human ovarian
      cancer cells.
AB  - BACKGROUND: Overexpression of superoxide dismutase 1 (SOD1) has been shown to be
      one of the factors involved in causing cisplatin resistance in ovarian cancer.
      Reduction of SOD1 expression is expected to restore, at least partially,
      cisplatin sensitivity in ovarian cancer chemotherapy. Here, we explored the
      potential of RNAi as a therapy for reversal of cisplatin resistance. MATERIALS
      AND METHODS: SOD1-specific small-interfering RNA (siRNA) was synthesized and
      transfected into cisplatin-resistant cell line A2780/CP prior to treatment with
      15 muM cisplatin. Cell survival was assessed by clonogenic assay. RESULTS: An
      enhanced cisplatin sensitivity was observed in the A2780/CP cells treated with
      SOD1-specific siRNA, compared to non-siRNA-treated or scrambled-siRNA-treated
      control cells. CONCLUSION: Specifically targeting SOD1 could lead to
      sensitization of cisplatin-resistant ovarian cancer cells, and SOD1 may be used
      as a potential target for chemosensitizers.

PMID- 20682986
TI  - Effects of anandamide on polyamine levels and cell growth in human colon cancer
      cells.
AB  - BACKGROUND: Anandamide (AEA) is an endogenous agonist for cannabinoid receptor
      CB1-R and seems to be involved in the control of cancer growth. Polyamines are
      compounds that play an important role in cell proliferation and differentiation.
      Our aim was to investigate the effect of AEA on the polyamine levels (putrescine,
      spermidine and spermine) and cell growth of three human colon cancer cell lines,
      positive for CB1-R. MATERIALS AND METHODS: After AEA treatment of DLD-1, HT-29
      and SW620 cells, polyamine analysis was performed by high-performance liquid
      chromatography (HPLC) and cell growth was measured by 3-(4,5 di-methylthiazol-2
      yl)-2,5-diphenyltetrazolium bromide (MTT) test. CB1 gene expression was
      determined using reverse transcription and polymerase chain reaction (RT-PCR).
      RESULTS: AEA significantly reduced polyamine levels and cell proliferation dose
      dependently when the tested cell lines were exposed for 24 h and 48 h. This
      inhibitory effect was mediated by CB1-R, since SR 1411716A, a selective CB-1
      receptor antagonist, was able to entirely antagonize the effect of AEA. CB1-R
      mRNA levels were enhanced after AEA treatment in DLD-1 cells, whereas no
      induction was found in HT-29 and SW620 cells. CONCLUSION: It appears that
      mechanisms by which AEA may affect growth of colon cancer cells involve a
      decrease in cell proliferation rate by reducing the polyamine levels.

PMID- 20682987
TI  - Expression of Fyn kinase modulates EMT in oral cancer cells.
AB  - Oral squamous cell carcinoma (SCC) is an aggressive tumor with a poor 5-year
      survival rate. Oral SCC can undergo epithelial to mesenchymal transition (EMT).
      We previously showed that the epithelial integrin alphavbeta6 complexes with Fyn
      kinase in oral SCC to promote EMT. Using immunofluorescence microscopy and
      Western blotting, we evaluated whether the expression of specific markers of EMT
      were influenced by modulating serum concentration (ie. growth factors). The SCC
      cultures were grown under contrasting levels of serum. In low serum (1%), Fyn
      promoted EMT; whereas suppression of Fyn kinase promoted the epithelial
      phenotype. However, when the SCC cells were grown in 10% serum, activation of Fyn
      had the reverse effect. Lastly, cell migration was evaluated under low serum
      conditions (1% FBS). Activation of Fyn promoted SCC cell migration and its
      suppression thwarted SCC migration toward FN. These results indicate that the
      activation of Fyn kinase as well as local growth factor concentration modulate
      EMT in oral SCC.

PMID- 20682988
TI  - Automated assessment of tumour microvascular architecture in vivo.
AB  - BACKGROUND: Quantitative analysis of tumour angiogenesis is an indispensable
      prerequisite for the development of novel antivascular treatment strategies. The
      aim of this study was to develop an automated analysis technique enabling
      quantitative assessment of complete tumour vascular networks non-invasively in
      vivo. MATERIALS AND METHODS: Experiments were performed in A-Mel-3 implanted in
      transparent dorsal skinfold chambers of the Syrian Golden hamster. Tumours were
      imaged in two dimensions by means of a computer controlled scanning-table
      combined with intravital microscopy. Functional vessel density was automatically
      quantified online with a digital imaging application package. RESULTS: Data for
      functional vessel density correlated excellently with data obtained by off-line
      video-based frame-by-frame analysis (R((S))=0.947, r(2)=0.959, n=48). CONCLUSION:
      This new technique enables automated, quantitative assessment of complete tumour
      vascular networks and therefore provides a promising tool to characterise changes
      of the entire tumour vascularity in response to antivascular treatment regimes.

PMID- 20682989
TI  - SMAD4 mediates mesenchymal-epithelial reversion in SW480 colon carcinoma cells.
AB  - BACKGROUND: Inactivation of the tumour suppressor gene SMAD4 is a genetically
      late event in gastrointestinal carcinogenesis. SMAD4 is a transmitter of growth
      inhibitory effects of transforming growth factor-beta (TGF-beta), an important
      tumour promoter capable of inducing an epithelial to mesenchymal transition
      (EMT). The role of SMAD proteins in late, tumour-promoting effects of TGF-beta is
      not well understood. MATERIALS AND METHODS: The change of molecular
      differentiation markers typical for EMT upon SMAD4 re-expression in SW480 cells
      was determined using Western blotting, immunohistochemistry and confocal laser
      microscopy. The influence of SMAD4 on the migration of SW480 cells was assessed
      in wound healing and pore migration assays. RESULTS: SMAD4 suppresses
      invasiveness and mediates reversion of SW480 cells from a mesenchymal-like to a
      polarized epithelial phenotype, with features of enterocyte-like differentiation.
      Moreover, SMAD4 reconstitution was associated with down-regulation of endogenous
      TGF-beta cytokines, suggesting that autocrine TGF-beta signaling may be involved
      in the EMT. CONCLUSION: These results provide further evidence for a role of
      SMAD4 as a regulator of invasion, a process of prime importance in carcinogenesis
      but hitherto poorly understood in molecular terms.

PMID- 20682990
TI  - Bone destruction by invading oral squamous carcinoma cells mediated by the
      transforming growth factor-beta signalling pathway.
AB  - BACKGROUND: Gingival squamous cell carcinoma (SCC) cells frequently invade
      mandibular bone, and this destruction is associated with a worse prognosis.
      However, the relationship between bone destruction and associated factors is
      unclear. In this study, the role and diagnostic utility of transforming growth
      factor-beta (TGF-beta) type I receptor (TbetaRI) in bone destruction of the
      mandible was investigated. PATIENTS AND METHODS: The expression of TbetaRI was
      explored by using an immunohistochemical method on paraffin-embedded tissues from
      21 cases of mandibular SCC. An inhibitor of the kinase activity of the TbetaRI
      (TbetaRI-I) was used to assess the role of TbetaRI in bone destruction by a human
      oral SCC cell line (HSC-2) that highly expresses TbetaRI. RESULTS: TbetaRI
      positive signals were closely associated with destructive invasion of the
      mandible by oral SCC cells. Consistent with these results, TbetaRI-I greatly
      reduced HSC-2 cell-induced bone destruction and osteoclast formation in vivo and
      in vitro. TbetaRI-I treatment reduced the expression of TNF-alpha, RANKL and
      connective tissue growth factor (CTGF/CCN2), all of which were up-regulated by
      TGF-beta in HSC-2 cells. CONCLUSION: These data demonstrated an important role
      for TGF-beta signalling in bone invasion by oral SCC cells, and suggest that the
      bone destruction is mediated by RANKL, TNF-alpha and CCN2.

PMID- 20682991
TI  - Combination therapy of 5-fluorouracil with rapamycin for hormone receptor
      negative human breast cancer.
AB  - AIM: To determine a novel chemotherapeutic concept for hormone receptor-negative
      and HER2-positive breast cancer, a high progression form of the disease for which
      treatment has been difficult. A combination therapy of 5-fluorouracil (5-FU) with
      rapamycin (Rap) was examined. MATERIALS AND METHODS: The growth inhibitory effect
      of treatment was evaluated by an MTT assay and cellular signal/apoptotic pathways
      were investigated by Western blotting and Hoechst 33342 staining. RESULTS: Rap
      was shown to induce an inhibitory effect on the phosphorylation of mTOR and
      p70S6K. The expression of thymidine synthase (TS) was decreased by Rap. The
      addition of 5-FU to Rap was found to increase cell death. The Hoechst 33342 assay
      showed that apoptosis was increased by the combination of 5-FU and Rap in
      comparison to 5FU alone. CONCLUSION: 5-FU is more effective in combination with
      the TS-reducing action of Rap, even for highly HER2-expressing breast cancer
      cells.

PMID- 20682992
TI  - Identification of a tumour associated antigen in lung cancer patients with
      asbestos exposure.
AB  - BACKGROUND: This study analysed the humoral immune response in asbestos exposed
      lung cancer patients to identify new surrogate markers of the carcinogenic risk
      in populations exposed to asbestos. METHODS AND RESULTS: A serological analysis
      identified five distinct antigens reactive with IgG derived from a lung cancer
      patient with high asbestos exposure. In one of the isolated antigens,
      quantitative RT-PCR indicated that annexin A2 (AnxA2) was overexpressed in lung
      cancer tissues and normal lung from patients with high asbestos exposure.
      Antibody against AnxA2 was detected in 9/15 (60%) of lung cancer patients with
      high asbestos exposure; however, in only 1/12 (8%) of lung cancer patients with
      low asbestos exposure. AnxA2 was also overexpressed in malignant mesothelioma
      cells, and the antibody was also positive in 8/15 (53%) of patients with
      malignant mesothelioma. CONCLUSION: The antibody titer against AnxA2 may be a
      potentially useful new diagnostic surrogate marker for asbestos-related lung
      cancer and malignant mesothelioma.

PMID- 20682993
TI  - Retrovirus-mediated Drosophila melanogaster multisubstrate deoxyribonucleoside
      kinase gene therapy of gastric cancer cells in vitro and in vivo.
AB  - AIM: The cytotoxicity of the Drosophila melanogaster multisubstrate
      deoxyribonucleoside kinase (Dm-dNK)/nucleoside analog system to human gastric
      carci-noma cells was evaluated in vitro and in vivo for the development of novel
      gene therapy for gastric cancer. METHODS: MGC-803 and BGC-823 cells were infected
      with retroviral vectors containing the Dm-dNK gene expressing Dm-dNK in its
      active form. [(3)H]-labeled substrates were used for enzyme activity assays and
      cytotoxicities were evaluated in vitro by MTT assay and annexin-V-FITC labeled
      FACS methods. Bystander effect assay was performed by MTT assay using a mixture
      of cells with and without expressed Dm-dNK. Anti-tumor efficacy was also examined
      in vivo. RESULTS: Nucleoside analogs were significantly more cytotoxic to Dm-dNK
      expressing cells than to their parental counterparts, and death was attributable
      to apoptosis. Implementation of the Dm-dNK/nucleoside analog system was
      associated with 'bystander' effects in vitro and suppressed the growth of MGC-803
      tumors in mice. CONCLUSION: The Dm-dNK/nucleoside analoguesystem possesses
      significant potential as suicide gene therapy for human gastric carcinoma.

PMID- 20682994
TI  - Epithelial versus endothelial CEACAM1 expression and angiogenesis in epididymal
      adenomatoid tumor.
AB  - BACKGROUND/AIM: To study the expression of the pro-angiogenic factor
      carcinoembryonic antigen-related cell adhesion molecule-1 (CEACAM1) in epididymal
      adeno-matoid tumor tissue, a very rare benign neoplasia, in relation to its
      vascularization. MATERIALS AND METHODS: Immunohistochemistry for CEACAM1 and for
      both endothelial markers CD31 and CD34 was performed in normal human epididymal
      and epididymal adenomatoid tumor tissue. The vessel density was calculated in
      four tumor regions with different degrees of vascularization in comparison to the
      vascularization of the normal epididymal tissue. RESULTS: CEACAM1 was found in
      normal epididymal epithelium, while the epithelium of tumor glands was mostly
      negative. Only few blood vessels and lymphatics in adenomatoid tumor tissue
      expressed CEACAM1. The assessment of vascularization revealed either equal or a
      significantly lower vessel density in some adenomatoid tumor regions in
      comparison to normal epididymal tissue. DISCUSSION: These data demonstrate that
      despite its epithelial down-regulation, CEACAM1 is not present in the majority of
      adenomatoid tumor blood vessels, which might be related to the lower angiogenic
      activity and benign behaviour of this tumor.

PMID- 20682995
TI  - Antiproliferative effect of a novel nitro-oxy derivative of celecoxib in human
      colon cancer cells: role of COX-2 and nitric oxide.
AB  - It has been shown previously that a novel nitrooxy derivative of celecoxib exerts
      antiproliferative and pro-apoptotic effects in human colon cancer cells. The aim
      of this study was to elucidate whether these biological properties depend on COX
      2 inhibition and/or NO release. Therefore, the derivative was decomposed into the
      parent compound celecoxib and the NO donor benzyl nitrate and the biological role
      of each was tested in COX-2-positive (HT-29) and -negative (SW-480) colon cancer
      cells. The main findings were that the nitro-oxy derivative behaved like
      celecoxib in HT-29 cells in terms of COX-2 and ERK/MAPK inhibition, as well as
      induction of apoptosis, while the benzyl nitrate had no such effects.
      Interestingly, the beta-catenin system was activated by the nitro-oxy derivative
      as well as by benzyl nitrate alone more potently than by the parent compound
      celecoxib, suggesting a possible regulatory role for NO. In SW480 cells, these
      activities were substantially less pronounced, suggesting the presence of COX-2
      dependent mechanisms in the modulation of these parameters.

PMID- 20682996
TI  - Calcitriol down-regulates human ether a go-go 1 potassium channel expression in
      cervical cancer cells.
AB  - BACKGROUND/AIM: Human ether a-go-go-1 (EAG1) potassium channels are promising
      anticancer targets. Calcitriol has antitumoural properties. This study
      investigated EAG1 regulation by calcitriol in normal and cancer cells. MATERIALS
      AND METHODS: Cancer cell lines from cervix, prostate, mammary gland, and normal
      placenta trophoblasts were cultured. Calcitriol was determined by HPLC. Gene and
      protein expression were assessed by real-time RT-PCR and western blot analysis,
      respectively. Calcitriol-synthesising enzyme CYP27B1 or vitamin D receptor (VDR),
      were transfected in cervical cancer SiHa cells. Cell proliferation was assayed
      with XTT. RESULTS: Calcitriol decreased EAG1 mRNA in all cell types, and EAG1
      protein and proliferation in SiHa cells. VDR antagonist ZK-159222 prevented the
      calcitriol effect on EAG1 mRNA. CYP27B1-transfected cells produced more
      calcitriol and less EAG1 mRNA. EAG1 mRNA was more potently inhibited by
      calcitriol in VDR-transfected cells. CONCLUSION: EAG1 is a calcitriol target in
      normal and cancer cells and calcitriol is a potential therapy for cervical
      cancer.

PMID- 20682997
TI  - RUNX3 promoter methylation in colorectal cancer: its relationship with
      microsatellite instability and its suitability as a novel serum tumor marker.
AB  - BACKGROUND/AIM: RUNX3 is a novel gastric cancer tumor suppressor. RUNX3 promoter
      hypermethylation is associated with many types of cancer, including colorectal
      cancer. Furthermore, the RUNX3 promotor is one of the CpG island methylator
      phenotype (CIMP)-specific promotors. CIMP is a distinct phenotype associated with
      microsatellite instability (MSI) in colorectal cancer. In this study, the
      suitability of the quantitative analysis of RUNX3 promoter hypermethylation as a
      novel serum tumor marker was investigated. Moreover, we investigated the
      relationship between RUNX3 promoter methylation and MSI in colorectal cancer.
      PATIENTS AND METHODS: A RUNX3 real-time quantitative methylation-specific PCR
      (RTQ-MSP) technique we developed was used to analyze the CpG sites in the RUNX3
      promoter of 119 colorectal tumors and 344 sera from colorectal cancer patients.
      MSI analysis of 119 colorectal tumors was performed with five microsatellite
      markers (BAT25, BAT26, D5S346, D2S123, and D17S250). RESULTS: Proximal colon
      tumors exhibited significantly higher RUNX3 methylation than their paired normal
      tissues (p=0.0438). Analysis of the clinicopathological parameters revealed that
      a proximal location (p=0.0054), lymphatic invasion (p<0.0001), and an advanced
      pathological stage (p=0.0018) were associated with significantly higher RUNX3
      methylation. Assessment of the relationship between RUNX3 methylation and tumor
      MSI revealed 11 out of 13 tumors with high-frequency MSI (85%) were positive for
      RUNX3 hypermethylation, significantly more than the tumors with low-frequency MSI
      or which were microsatellite stable (34%, p=0.0070). In preoperative sera from
      344 colorectal cancer patients, significantly higher RUNX3 methylation was
      associated with lymphatic invasion (p=0.0487) and an advanced pathological stage
      (p=0.0466). Post-operative follow-up data revealed that recurrence cases
      exhibited significantly higher preoperative serum RUNX3 methylation than non
      recurrence cases (p=0.0003). Concomitant analysis of carcinoembryonic antigen
      (CEA) levels in the preoperative sera showed that 17.7% (61/344) were CEA
      negative but RUNX3 methylation-positive, which means assessing both serum RUNX3
      methylation and CEA should improve diagnosis of colorectal carcinoma. CONCLUSION:
      RTQ-MSP-based quantification of serum RUNX3 methylation is useful for the
      detection and monitoring of colorectal cancer.

PMID- 20682998
TI  - Computational analysis of mTOR signaling pathway: bifurcation, carcinogenesis,
      and drug discovery.
AB  - Molecularly targeted therapeutics provides potentially more reliable performance
      while significantly reducing toxicity in comparison with chemotherapy. For cancer
      signaling networks which are usually complex, multiple molecules should be
      simultaneously targeted in order to stay in tune with the control mechanisms of
      the network and to achieve the maximum synergistic effects. Mathematical modeling
      and computer simulation are important in reproducing the dynamics of the network,
      some of which may correspond to healthy or cancer phenotypes. More importantly,
      the effects of multiple molecules can be simulated by perturbing many parameters
      in the model. In this paper, through the example of the mTOR signaling pathway,
      we demonstrate that computational analysis can provide great insights into cancer
      pathogenesis and the possible therapeutic interventions. In particular, we
      discovered a composite parameter which summarizes the synergistic effects of four
      different parameters. The geometry of the parameter space could be helpful in the
      development of a low dosage, minimal toxicity drug to cure cancer.

PMID- 20682999
TI  - MACC1 as a marker for advanced colorectal carcinoma.
AB  - BACKGROUND: Recently, Stein et al. identified the metastasis-associated in colon
      cancer 1 (MACC1) gene by genome-wide search for differentially expressed genes in
      human colon cancer tissues and metastases. PATIENTS AND METHODS: We analyzed
      MACC1 expression levels in 52 colorectal cancer samples using quantitative real
      time polymerase chain reaction (QRT-PCR). RESULTS: We found that MACC1 expression
      showed significant correlation with peritoneal dissemination (p=0.042) and higher
      stage of TNM classification (p=0.007). CONCLUSION: These results suggest that
      MACC1 is more frequently expressed in advanced colorectal carcinomas.

PMID- 20683000
TI  - Overexpression of MMP-13 gene in colorectal cancer with liver metastasis.
AB  - Matrix metalloproteinase-7 (MMP-7), MMP-9, MMP-13, and tissue inhibitor of matrix
      metalloproteinase-1 (TIMP-1) are considered to have important roles in the
      invasiveness and outcomes of colorectal cancer (CRC). This study examined the
      clinicopathological significance of the relative expression of these genes in
      patients with colorectal cancer, especially as related to liver metastasis. The
      study analysed surgical specimens of cancer tissue and adjacent normal mucosa
      obtained from 202 patients with untreated colorectal cancer. MMP-7, MMP-9, MMP
      13, TIMP-1, and beta-actin mRNA of cancer tissue and adjacent normal mucosa were
      measured by quantitative real-time, reverse-transcriptase polymerase chain
      reaction. Expression levels of MMP-7, MMP-9, MMP-13 and TIMP-1 were higher in
      cancer tissue than in adjacent normal mucosa. On analysis of the relations
      between gene expression and clinicopathological factors, MMP-13 expression was
      found to correlate with liver metastasis. Moreover, MMP-13 expression levels were
      higher in tumour tissue with liver metastasis than in that without liver
      metastasis. It is concluded that MMP-13 gene expression is a useful predictor of
      liver metastasis in patients with CRC.

PMID- 20683001
TI  - Methylation of the p16 gene is frequently detected in lymphatic-invasive gastric
      cancer.
AB  - BACKGROUND: A tumor suppressor gene, p16, was found to harbor promoter
      methylation associated with the loss of protein expression in cancer cells,
      suggesting that p16 inactivation due to promoter methylation may be important for
      gastric tumorigenesis. PATIENTS AND METHODS: The methylation status of the p16
      gene was examined in primary carcinomas and the corresponding normal tissues
      derived from 49 patients with gastric cancer using quantitative methylation
      specific PCR (qMSP) and the correlation between the methylation status and the
      clinicopathological findings was evaluated. RESULTS: Aberrant methylation of the
      p16 gene was detected in 17 out of the 49 (34%) primary gastric carcinomas,
      suggesting that the aberrant methylation of p16 is frequently observed in gastric
      carcinomas. The clinicopathological data were then correlated with these results.
      Significant differences were observed with lymphatic invasion (p=0.046) and tumor
      site (p=0.010). CONCLUSION: p16 might act as a tumor suppressor in gastric
      carcinomas and appears to be more frequently methylated in lymphatic-invasive
      gastric carcinomas.

PMID- 20683002
TI  - Comprehensive analysis of genes involved in the malignancy of gastrointestinal
      stromal tumors.
AB  - BACKGROUND: During tumorigenesis of gastrointestinal stromal tumors (GISTs), the
      most frequent changes are reported to be gain-of-function mutations in the C-KIT
      proto-oncogene. However, we speculated that additional genetic alterations are
      required for the progression of GISTs. PATIENTS AND METHODS: Using 15 cases
      diagnosed with GISTs, we searched for novel indicator genes by microarray
      analyses using an Oligo GEArray(R) PI3K-AKT Signaling Pathway Microarray Kit. In
      addition, we analyzed the mutational status of C-KIT and the proliferation status
      indicated by the Ki-67 index. RESULTS: The tumor localizations of the 15 GISTs
      were as follows: 8 in the stomach; 2 in the small intestine; 2 in the mesentery;
      1 in the duodenum; 1 in the rectum; and 1 in liver. Regarding the C-KIT gene
      analysis, mutations in exon 11 were detected in 11 out of 13 patients. In 1 out
      of the 13 patients, mutations were detected in both exons 11 and 13. No genetic
      abnormalities were identified in 1 patient. The Ki-67 labeling indices were
      significantly lower for the low-risk and intermediate-risk groups than for the
      high-risk group (p=0.0440). No specific genes were overexpressed in the >1% Ki-67
      group. Regarding the primary lesion sites, the following 6 genes were
      overexpressed in tumors in the stomach: RBL2, RHOA, SHC1, HSP90AB1, ACTB and
      BAS2C. CONCLUSION: Gene analysis is currently only useful for diagnostic
      assessment and predicting therapeutic effects. However, it may be possible for
      new malignancy-related factors to be identified by comparing and investigating
      gene expression levels and other factors using such analyses.

PMID- 20683003
TI  - Combined effects of bisphosphonate and radiation on osteosarcoma cells.
AB  - Antitumour effects of third-generation bisphosphonates (BPs), such as zoledronic
      acid (ZOL), and the combined effects of ZOL with other anticancer agents against
      osteosarcoma cells have been reported previously. The aim of this study was to
      identify further combined antitumour effects using BPs and radiation in
      osteosarcoma cell lines. MATERIALS AND METHODS: Cell proliferation, cell cycle
      analysis, and nuclear morphology were examined in each osteosarcoma cell line
      divided into three groups (ZOL alone, radiation alone and the ZOL/radiation
      combination). RESULTS: Combined therapy (low-concentration ZOL and low-dose
      radiation) had significant growth inhibitory effects compared to the use of ZOL
      or radiation individually. Flow cytometric analysis revealed an increase in cells
      in the sub-G(1) phase by combined treatment, and apoptotic cells were also
      observed. CONCLUSION: These findings suggest that combination therapy using BPs
      and radiation may be a promising therapy for osteosarcoma, producing fewer side
      effects and complications in the near future.

PMID- 20683004
TI  - Effect of astaxanthin supplementation on inflammation and cardiac function in
      BALB/c mice.
AB  - Astaxanthin is an antioxidant with immunomodulatory, anti-inflammatory and
      anticancer properties. This study evaluated the use of dietary astaxanthin to
      decrease oxidative stress and improve cardiac function, thereby providing a
      potential cardioprotective supplement. Female BALB/c mice (8 weeks of age) were
      fed a semi-synthetic diet containing 0, 0.02 or 0.08% astaxanthin for 8 weeks.
      Cardiac function was assessed by echocardiography bi-weekly, and blood and tissue
      samples were collected at 8 weeks. Plasma astaxanthin concentrations increased
      (p<0.05) dose-dependently to 0.5 and 4 mumol/l in the astaxanthin-supplemented
      mice. Blood glutathione concentrations and lymphocyte mitochondrial membrane
      potential were not significantly affected by astaxanthin treatment. However, mice
      fed 0.08% astaxanthin had higher (p<0.05) heart mitochondrial membrane potential
      and contractility index compared to the control group. These results support the
      possible use of dietary astaxanthin for cardiac protection.

PMID- 20683005
TI  - Colorectal cancer and genetic polymorphism of DNA double-strand break repair gene
      XRCC4 in Taiwan.
AB  - The DNA repair gene X-ray repair complementing defective repair in Chinese
      hamster cells 4 (XRCC4) is thought to play a major role in the caretaking of the
      whole genome via double-strand break repair. However, the association of
      polymorphic variants of XRCC4 with colorectal cancer susceptibility has never
      been reported. In this hospital-based case-control study, the association of
      XRCC4 polymorphisms C-1622T (rs7727691), G-1394T (rs6869366), G-652T (rs2075685),
      C-571T (rs2075686), intron 3 DIP (rs28360071), S247A (rs3734091) and intron 7 DIP
      (rs28360317) with colorectal cancer risk in a Taiwanese population was
      investigated. The genotypes of XRCC4 of 370 patients with colorectal cancer and
      370 age- and gender-matched healthy controls were determined by polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. We found
      significant differences in the genetic and allelic frequencies of the XRCC4 G
      1394T between the colorectal cancer and control groups (p=0.0003 and 8.32 x 10(
      5), respectively). The distributions of other genetic polymorphisms between cases
      and the control group were not significantly different. We conclude that the G
      allele of XRCC4 G-1394T may contribute to colorectal carcinogenesis and may be
      useful for early detection of colorectal cancer.

PMID- 20683006
TI  - Construction and molecular characterization of human chimeric T-cell antigen
      receptors specific for carcinoembryonic antigen.
AB  - BACKGROUND: Chimeric T-cell antigen receptors (CAR) provide a promising approach
      for adoptive T-cell immunotherapy of cancer. Extensive studies on CARs have been
      conducted, but the detailed molecular mechanisms of the activation of a CAR
      grafted T-cell remain ambiguous. This study constructed a CAR bearing anti
      carcinoembryonic antigen (CEA) derived from a human monoclonal antibody (clone C2
      45), and investigated the molecular basis of the CAR-mediated activation in
      Jurkat T-cells. MATERIALS AND METHODS: A gene of a single chain fragment variable
      (scFv) specific for CEA was functionally cloned by the phage display method. The
      scFv gene was fused to human cDNAs coding for transmembrane and cytoplasmic
      domains of CD28 and an intracellular domain of CD3zeta. The resultant CAR45
      28zeta was transiently expressed in Jurkat cells, and T-cell activation was
      examined by Western blotting and a cytokine production assay. A fluorescent
      protein-tagged ZAP-70 was used to determine whether CAR45-28zeta and ZAP-70 were
      co-localized at the cell surface by confocal microscopy. RESULTS: A Western blot
      analysis showed CAR45-28zeta activated the ERK JNK, and p38 pathways in a CEA
      dependent manner. An immunofluorescent analysis revealed the CEA-dependent
      formation of the signaling clusters at the antigen-CAR interface. CONCLUSION:
      CAR45-28zeta induced a wild-type T-cell receptor-like molecular event upon CEA
      binding, suggesting that this CAR fused gene may be useful for cancer therapy.

PMID- 20683007
TI  - Heterogeneous expression of serine protease inhibitor maspin in ovarian cancer.
AB  - Ovarian cancer (OC) is a disease with poor prognosis, and molecular markers are
      needed to improve understanding of disease progression and resultant treatment.
      Only limited data concerning the expression of maspin, a serine protease
      inhibitor, in ovarian cancer (OC) are available. This study investigates the
      prognostic value of maspin expression (ME) in various OC cell lines and clinical
      tissue specimens from OC patients. PATIENTS AND METHODS: Tumour purified mouse
      anti-human maspin monoclonal antibody was applied to tissue specimens from 87 OC
      patients. ME was recorded by an immunoreactive score, which was correlated with
      grading, stage, histopathological subtypes and overall survival. Additionally ME
      was evaluated in established ovarian cancer cell lines (HEY, SKOV3, OVCAR3/8) and
      paclitaxel- and docetaxel-resistant HEY cells by QRT-PCR. RESULTS: There was
      significant correlation between cytoplasmatic ME and overall survival (p<0.05).
      OC patients with high levels of ME had a median survival of 28 vs. 57 months for
      those with low levels. Significant differential ME was detected between benign,
      borderline ovarian lesions and OC, as well as among different tumour gradings.
      Normal ovarian epithelial cells expressed less maspin than ovarian cancer cells
      as measured by QRT-PCR. Docetaxel- and paclitaxel-resistant ovarian cell lines
      showed an even higher level of ME, suggesting an unfavourable role of ME in OC
      cell lines. CONCLUSION: Maspin is expressed differentially in OC, and low
      expression levels of maspin are correlated with a longer survival.

PMID- 20683008
TI  - Domain organization and properties of LB lysozyme crystals down to submicron
      size.
AB  - New topographic details appeared evident in protein crystal buffered with
      glycerol solution native on mica by atomic force microscopy and after laser
      irradiation on glass by light microscopy. This observation indicates the
      existence of distinct domains in the 3D crystal organisation that are quite
      different in size and number between the lysozyme crystals grown by Langmuir
      Blodgett (LB) nanotemplate with respect to traditional hanging-drop vapour
      diffusion. Nanodiffraction by highly focused synchrotron radiation of laser cut
      submicron crystals confirmed the atomic structure of all residues of LB lysozyme
      crystals as being the most resistant to radiation damage. Crystals grown by LB
      nanotemplate still diffracted at good resolution after several steps of X-ray
      'burning', while the classical crystals decayed very quickly at the same
      exposure.

PMID- 20683009
TI  - Epithelial and stromal expression of syndecan-2 in pancreatic carcinoma.
AB  - The aim of the study was to determine the expression and prognostic role of
      syndecan-2 in patients with pancreatic adenocarcinoma. PATIENTS AND METHODS:
      Syndecan-2 expression and its relationship with established prognostic features
      were assessed in a series of 53 patients with pancreatic ductal adenocarcinoma.
      RESULTS: Epithelial expression was observed in 23 (43.4%) and stromal in 30
      (56.6%) pancreatic carcinomas, respectively. In normal pancreatic tissue, the
      epithelial expression was moderate or strong in single or small clusters of
      acinar cells and negative in ductal cells. Normal pancreatic stroma did not
      express syndecan-2. Statistical analysis showed that stromal expression had no
      influence on survival but epithelial expression was positively correlated with
      survival time, and patients with higher epithelial syndecan-2 expression had a
      distinctly longer survival (p=0.029). CONCLUSION: Our results support a potential
      role for syndecan-2 in pancreatic carcinogenesis and cancer progression.
      Moreover, expression of syndecan-2 might serve as a prognostic marker.

PMID- 20683010
TI  - PTHrP regulates angiogenesis and bone resorption via VEGF expression.
AB  - BACKGROUND: Parathyroid hormone-related protein (PTHrP) is a key regulator of
      osteolytic metastasis of breast cancer (BC) cells, but its targets and mechanisms
      of action are not fully understood. This study investigated whether/how PTHrP (1
      34) signaling regulates expression of vascular endothelial growth factor (VEGF)
      produced by BC cells. MATERIALS AND METHODS: A mouse model of bone metastasis was
      prepared by inoculating mice with tumour cell suspensions of the human BC cell
      line MDA-MB-231 via the left cardiac ventricle. VEGF expression was examined by
      Western blot and real-time RT-PCR analysis, as well as by confocal microscopy in
      the bone microenvironment. RESULTS: PTHrP was expressed in cancer cells producing
      PTH/PTHrP receptor and VEGF that had invaded the bone marrow, and PTHrP was up
      regulated VEGF in MDA-MB-231 in vitro. The culture medium conditioned by PTHrP
      treated MDA-MB-231 cells stimulated angiogenesis and osteoclastogenesis compared
      with control medium, giving a response that was inhibited by VEGF-neutralizing
      antibody treatment. Inhibition of protein kinase C (PKC) prevented PTHrP-induced
      extracellular signal-regulated kinase (ERK1/2) and p38 activation, and PTHrP
      induced VEGF expression. CONCLUSION: PTHrP plays an important role in modulating
      the angiogenic and bone osteolytic actions of VEGF through PKC-dependent
      activation of an ERK1/2 and p38 signaling pathway during bone metastasis by
      breast cancer cells.

PMID- 20683011
TI  - IL-8 and IL-6 bystander signalling in human glioblastoma cells exposed to gamma
      radiation.
AB  - BACKGROUND: Exposure of cells to ionising radiation causes the release of several
      factors, such as cytokines, which are likely to be involved in some biological
      effects occurring in the irradiated cells and in the neighbouring non-irradiated
      cells (i.e. bystander effect). MATERIALS AND METHODS: The release of interleukin
      (IL)-6 and IL-8 in the culture medium of irradiated human glioblastoma cells was
      investigated using an ELISA technique. Immunocytochemistry was used to
      investigate the expression of corresponding cell membrane receptors in irradiated
      cells and in cells cultured with medium collected from irradiated cells. RESULTS:
      The exposure to radiation determined an increase of IL-6 concentration which was
      dose dependent at 20 hours, whereas IL-8 release was lower than control shortly
      after irradiation but increased with time, in particular at the dose of 0.5.
      CONCLUSION: Our data suggest that these cytokines are differently modulated by
      radiation and are likely to play a role in the transmission of radiation-induced
      response, probably orchestrating the inflammatory microenvironment of the tumour.

PMID- 20683012
TI  - Melphalan modulates the expression of E7-specific biomarkers in E7-Tg mice.
AB  - HPV oncoproteins are selectively retained and expressed in HPV infected carcinoma
      cells. The E7 oncoprotein interacts with the tumour suppressor Rb, and leads to
      the progression of oncogenesis. In a previous study, E7 biomarkers were
      identified in E7 Tg mice. In this study, in order to investigate whether a
      genotoxic carcinogen would modulate carcinogenesis in the E7-Tg mice, an
      anticancer drug, melphalan, was intraperitoneally injected into E7-Tg mice for
      eight weeks at two-day intervals and then genes and proteins were analysed using
      Omics approaches and RT-qPCR. RT-qPCR was performed to confirm whether E7
      biomarkers would be modulated by melphalan treatment in E7-Tg mice, revealing
      that up-regulated E7 markers such as cyclin B1, CD166, and actin alpha1 were down
      regulated, whereas expression of down-regulated E7 markers such as vimentin was
      restored by melphalan treatment. These results suggest that melphalan inhibits
      carcinogenesis via modulating E7-specific genes and proteins expressed in the
      lung tissues of E7 Tg mice.

PMID- 20683013
TI  - Cell-free circulating DNA: Diagnostic value in patients with renal cell cancer.
AB  - OBJECTIVES: To analyse the diagnostic and prognostic value of cell-free DNA in
      patients with renal cell carcinoma (RCC). PATIENTS AND METHODS: Cell-free DNA was
      measured in 35 patients with RCC and 54 healthy individuals using quantitative
      real-time PCR. ACTB-106 detects fragmented cell-free DNA due to apoptosis and
      ACTB-384 detects long DNA fragments by necrosis. DNA-Integrity (ACTB-384/ACTB-106
      ratio) served as measure of DNA fragmentation. RESULTS: Levels of both DNA
      fragments were increased in RCC patients compared to healthy individuals (ACTB
      384: 1.77 vs. 0.61ng/ml, p=0.0003; ACTB-106: 1.31ng/ml vs. 0.77 ng/ml p=0.003).
      Receiver operator characteristic analysis (ROC) showed at a threshold level of
      1.03 ng/ml for ACTB-106 68.6%, sensitivity and 70.4% specificity (AUC: 0.69). ROC
      analysis showed at a threshold level of 1.70 ng/ml for ACTB-384 57.1%,
      sensitivity and 81.5% specificity (AUC: 0.73). DNA integrity was increased in RCC
      (1.07 vs. 0.72 p=0.04). In vascular invasion the DNA integrity was reduced
      (p=0.003). CONCLUSION: Cell-free-DNA levels are increased in RCC. The DNA
      integrity indicates mostly necrotic origin in RCC.

PMID- 20683014
TI  - Role of caspases and CD95/Fas in the apoptotic effects of a nucleotide analog
      PMEG in CCRF-CEM cells.
AB  - BACKGROUND/AIM: 9-[2-(phosphonomethoxy)ethyl] guanine (PMEG) is a guanine acyclic
      nucleotide analog whose targeted prodrugs are being investigated for chemotherapy
      of lymphomas. Its antiproliferative effects have been attributed to cell cycle
      arrest and induction of apoptosis, however, the underlying mechanisms remain
      poorly understood. The objective of this study was to determine the requirements
      for caspase and CD95/Fas activation in PMEG-induced apoptosis. Additionally, the
      influence of PMEG on cell cycle regulatory proteins was explored. MATERIALS AND
      METHODS: CCRF-CEM cells were exposed to PMEG with/without caspase inhibitor or
      anti-Fas blocking antibody and assayed for phosphatidyl serine externalization,
      mitochondrial depolarization and the cleavage of procaspase 3 and the nuclear
      protein poly (ADP-ribose) polymerase (PARP). RESULTS: Despite an observed
      increase of caspase 3, 8 and 9 proteolytic activity, neither pretreatment of the
      cells with cell-permeable caspase inhibitors nor blocking the death receptor with
      anti-Fas antibody did prevent apoptosis induced by PMEG. CONCLUSION: PMEG-induced
      apoptosis is caspase- and CD95/Fas-independent.

PMID- 20683015
TI  - Expression of p27, p21(WAF/Cip1), and p16(INK4a) in normal oral epithelium, oral
      squamous papilloma, and oral squamous cell carcinoma.
AB  - AIM: To characterize the immunohistochemical expression of p27, p21(WAF/Cip1) and
      p16(INK4a) in normal oral epithelium, oral squamous papilloma and oral squamous
      cell carcinoma. MATERIALS AND METHODS: Immunohistochemical staining for p27,
      p21(WAF/Cip1) and p16(INK4a) was evaluated in 32 samples of normal oral squamous
      epithelium, 30 samples of oral squamous papilloma, and 34 samples of oral
      squamous cell carcinoma. RESULTS: Statistically significant differences (p<0.05)
      were found in p27 expression when comparing ordinary mucosa and oral squamous
      papilloma with the oral squamous cell carcinoma samples. Regarding p21(WAF/Cip1)
      expression, no statistically significant differences (p>0.05) were noticed. In
      the same way, no significant statistically differences (p>0.05) were observed for
      p16(INK4a) among groups. CONCLUSION: Taken together, these findings indicate that
      p27 is closely involved in malignant transformation of oral mucosa cells, and may
      be a reliable biomarker for this purpose.

PMID- 20683016
TI  - Analysis of chemotherapeutic response heterogeneity and drug clustering based on
      mechanism of action using an in vitro assay.
AB  - BACKGROUND: Cancer chemotherapeutic treatment is a complex scientific task. The
      ChemoFx Drug Response Marker (DRM) assists physicians in identifying treatment
      protocols likely to be effective for specific patients. MATERIALS AND METHODS:
      The ChemoFx DRM was used to study drug response in vitro. Established human
      cancer cell lines and primary cultures of patient tumor specimens were challenged
      with chemotherapeutic agents to observe response of multiple tumor samples and
      determine whether drugs with similar mechanisms of action elicit similar
      response. RESULTS: These studies demonstrated heterogeneous response among
      patient tumor samples and clustering of drug response with similar mechanisms of
      action. Also highlighted was the reproducibility of ChemoFx DRM and its utility
      in characterizing tumor response to chemotherapy. CONCLUSION: Heterogeneous drug
      responses observed in vitro were similar to those observed clinically. Response
      characteristics were similar for drugs with similar mechanisms of action,
      suggesting response heterogeneity is determined at a cellular and molecular
      level.

PMID- 20683017
TI  - Antiangiogenic activities and cisplatin-combined antitumor activities of
      BPR0L075.
AB  - BACKGROUND: Antimitotic tubulin-binding BPR0L075 is structurally analogous to the
      vascular-disrupting combretastatin A-4. MATERIALS AND METHODS: In vitro/in vivo
      models of endothelial cells cultures, Matrigel plug assay, tumor-bearing nude
      mice, and murine leukemia cells-inoculated mice were utilized to evaluate
      BPR0L075 for antiangiogenic and antitumoral activity spectra. RESULTS: BPR0L075
      concentration-dependently inhibited proliferation and migration of human
      umbilical vein endothelial cells (HUVECs), disrupted capillary tube formations of
      HUVECs and rat aorta endothelial cells, and suppressed in vivo VEGF-mediated
      angiogenesis in Matrigel plugs in mice. Besides inhibiting the colony growth of
      cancer cells, BPR0L075 suppressed growth of subcutaneously-xenografted human
      lung, colorectal, and cervical solid tumors in nude mice. Combination treatments
      of BPR0L075 plus cisplatin, compared to either agent alone, demonstrated a
      stronger growth inhibition against the tumor xenografts in nude mice and longer
      lifespan in the leukemia mice. CONCLUSION: BPR0L075 is an antitumoral and
      antiangiogenic agent and potentiates the anticancer activity of cisplatin.

PMID- 20683018
TI  - A3 adenosine receptor antagonist, truncated Thio-Cl-IB-MECA, induces apoptosis in
      T24 human bladder cancer cells.
AB  - BACKGROUND: Human A(3) adenosine receptor (A(3)AR) plays an essential role in
      several physiopathological processes. Thus far, A(3)AR-selective ligands have
      been evaluated as anti-inflammation and anticancer therapeutic agents. Among
      these ligands, truncated thio-Cl-IB-MECA is a newly reported antagonist, and its
      function has not been studied. MATERIALS AND METHODS: Cell viability was measured
      by MTS assay. Cell cycle progression was analysed by propidium iodide (PI) flow
      cytometric assay. The apoptotic effects were investigated by Hoechst staining and
      annexin V-FITC/PI staining. The signal-transduction mechanism was explored by
      Western blot. RESULTS: Truncated thio-Cl-IB-MECA induced the growth arrest of T24
      cells at sub-G(1) phase and provoked apoptosis but not necrosis. Apoptotic death
      was mediated by the activation of extracellular signal-regulated kinase (ERK) and
      c-Jun N-terminal kinase (JNK). CONCLUSION: Since truncated thio-Cl-IB-MECA
      induces anti-proliferation and apoptotic effects via ERK and JNK activation, it
      may function as an anticancer agent in human bladder cancer cells.

PMID- 20683019
TI  - Hypoxia and activated VEGF/receptor pathway in multiple myeloma.
AB  - BACKGROUND/AIM: Intensified angiogenic pathways are associated with poor
      prognosis and resistance of multiple myeloma (MM) cells to therapy. The links of
      the VEGF pathway with the hypoxia inducible factor (HIF) expression in MM are
      herein investigated. MATERIALS AND METHODS: The vascular density (VD) and the
      HIF/VEGF/VEGF-receptor expression in the bone marrows of 106 MM cases were
      studied using immunohistochemistry. RESULTS: HIF1alpha and HIF2alpha were
      expressed strongly in 33% and 13.2% of the cases, respectively. VEGFR and the
      phosphorylated (active) form of VEGFR2/KDR receptors were up-regulated in 42.5%
      and 36.8% of cases, respectively. Both HIF1alpha and HIF2alpha were significantly
      linked with high VD and VEGF expression. Moreover, the expression of the
      phosphorylated (active) form of VEGFR2/KDR was significantly linked with VEGF and
      HIF1alpha expression. The HIF/VEGF/VEGF-receptor pathway is up-regulated in
      approximately 40% of MM cases and linked with increased angiogenesis. Survival
      analysis in 37 evaluable patients showed a significantly worse prognosis in cases
      with high VD. CONCLUSION: HIFs and VEGF are up-regulated in a significant
      percentage of MM and are strongly related to each other. Targeting HIFs and the
      VEGF/receptor autocrine loop may prove of importance in the treatment of the
      disease.

PMID- 20683020
TI  - Immunhistochemical analysis for expression of calpain 1, calpain 2 and
      calpastatin in endometrial cancer.
AB  - BACKGROUND: Calpains (CAPN) are intracellular, non-lysosomal cytoplasmic cysteine
      endopeptidases and they are expressed ubiquitously. Their endogenous specific
      inhibitor is calpastatin. When calcium is present, calpastatin and calpain attach
      to each other, inhibiting the protease. The calpain system plays an important
      role in many processes including apoptosis, necrosis, ischaemia and exocytosis.
      The role of calpains in pathogenesis or further tumour progression has been
      proved in related studies. This study focused on the expression of the enzymes
      calpain 1, calpain 2 and the inhibitor calpastatin in normal and malignant
      endometrial tissue. MATERIALS AND METHODS: Immunohistochemical stainings were
      performed on paraffin slices and staining intensity, percentage of positive cells
      and international ratio score were evaluated. RESULTS AND CONCLUSION: The
      endometrial carcinoma showed a higher expression of calpastatin than benign
      endometrial tissue.

PMID- 20683021
TI  - Expression of ki-67 antigen and caspase-3 protein in benign lesions and
      esophageal carcinoma.
AB  - BACKGROUND: The present study aimed to evaluate apoptosis and cell proliferation
      alterations in esophageal benign lesions in comparison to esophageal carcinomas.
      MATERIALS AND METHODS: Immunohistochemistry was performed for caspase-3 protein
      (CPP32) and Ki-67 antigen expression in the esophageal mucosa from patients with
      Chagas disease (CD) with and without megaesophagus (CM), chronic esophagitis
      (CE), esophageal carcinoma (ESCC) and in normal mucosa (NM). RESULTS: The Ki-67
      labeling index (LI) was similar in all groups (range: 30%-48%), having no
      statistically significant difference among the groups. Positive CPP32
      immunostaining was observed with similar frequency in the CD (30.8%), CM (30.4%)
      and CE (34.8%) groups, but it was increased in the ESCC group (55.5%); however,
      it was not statistically different from the other groups. No associations among
      the levels of CPP32 and Ki-67 expression were observed in the various groups,
      neither among parameters such as age, gender or alcohol and tobacco consumption.
      CONCLUSION: There were no evident changes in cell proliferation and apoptosis in
      benign lesions studied.

PMID- 20683022
TI  - Curcumin alters the migratory phenotype of nasopharyngeal carcinoma cells through
      up-regulation of E-cadherin.
AB  - BACKGROUND: Curcumin is a natural polyphenol. It is a potent suppressor of
      nuclear factor kappa B (NF-kappaB). High NF-kappaB levels have suppressive effect
      on E-cadherin (molecule related to cell-cell adhesion) in nasopharyngeal
      carcinoma (NPC) cells. We hypothesized that suppressing NF-kappaB by curcumin
      could up-regulate E-cadherin expression in NPC cells. MATERIALS AND METHODS: NPC
      cell lines HK1 and HONE1 were used. Real-time quantitative PCR and Western
      blotting were used to examine the expression changes of NF-kappaB and E-cadherin.
      A mouse xenograft model was used to validate the results. RESULTS: With curcumin
      treatment, NF-kappaB was down-regulated and E-cadherin was up-regulated in NPC
      cells. The negative correlation of NF-kappaB and E-cadherin was confirmed in the
      mouse xenograft model. CONCLUSION: Our results suggest that curcumin could be
      used in preventing NPC migration by suppressing NF-kappaB and activating E
      cadherin expression.

PMID- 20683023
TI  - Heterogeneity of radiation- and TNF-alpha-induced programmed cell death in
      carcinoma, sarcoma and lymphoma cell lines.
AB  - AIM: To characterize the interaction of tumour necrosis factor alpha (TNF-alpha)
      and ionising radiation in six sarcoma, lymphoma and carcinoma cell lines.
      MATERIALS AND METHODS: Cells were characterized regarding annexin V/propiduim
      iodine affinity and caspase-3 status after application of TNF-alpha, radiation,
      or combined treatment. RESULTS: Three cell lines showed similar results with
      additive effects of TNF-alpha and radiation in both assays. The other three cell
      lines significantly differed regarding the detection of apoptotic cells between
      treatment conditions (radiation and/or TNF application) and between the two
      apoptosis assays. CONCLUSION: The interaction between TNF-alpha and radiation
      differs between tumour entities and cannot be described by using only one
      parameter.

PMID- 20683024
TI  - Carbonyl cyanide p-(trifluoromethoxy) phenylhydroazone induces caspase
      independent apoptosis in As4.1 juxtaglomerular cells.
AB  - Carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone (FCCP) is an uncoupler of
      mitochondrial oxidative phosphorylation in mitochondria. This study evaluated the
      effects of FCCP on the growth of juxtaglomerular As4.1 cells in relation to the
      cell cycle and apoptosis. FCCP inhibited the growth of As4.1 cells with an IC(50)
      of approximately 10 muM at 48 hours. DNA flow cytometry indicated that FCCP did
      not induce the specific phase arrests of the cell cycle. This agent efficiently
      reduced mitochondrial membrane potential (MMP; DeltaPsi(m)) levels within 1 hour
      and dose-dependently induced loss of MMP (DeltaPsi(m)) at 48 h. FCCP also induced
      apoptosis in As4.1 cells, as evidenced by sub-G(1) cells and annexin V binding
      assay. This apoptotic process was accompanied by caspase-3 activation and PARP
      cleavage. Although caspase-3 inhibitor significantly reduced the activity of
      caspase-3, all of the caspase inhibitors tested in this study failed to rescue
      As4.1 cells from FCCP-induced cell death. In conclusion, this study demonstrated
      that FCCP, as a mitochondria-damaging agent, potently induces apoptosis in As4.1
      juxtaglomerular cells via a caspase-independent manner.

PMID- 20683025
TI  - gamma-Tocotrienol controls proliferation, modulates expression of cell cycle
      regulatory proteins and up-regulates quinone reductase NQO2 in MCF-7 breast
      cancer cells.
AB  - BACKGROUND: Tocotrienols, a subgroup of the vitamin E family, have demonstrated
      antioxidant and anticancer properties. Differential growth responses among
      different types of tocotrienols have been observed in breast cancer cells;
      however, specific bioactivity of each individual tocotrienol remains to be
      elucidated. MATERIALS AND METHODS: In this study, the effects of gamma
      tocotrienol were examined with regard to its ability to suppress cell
      proliferation via modulation of cell cycle regulatory protein expression, and
      also from the perspective of control of cellular oxidoreductive status through
      regulation of detoxification enzymes, e.g., quinone reductase NQO2, using
      estrogen receptor-positive MCF-7 human breast cancer cells. RESULTS: It was shown
      that treatment by gamma-tocotrienol suppressed MCF-7 cell proliferation in a dose
      and time-dependent manner. Growth suppression by gamma-tocotrienol was
      accompanied by changes in the levels of cell cycle regulatory proteins, notably,
      Rb/E2F complex, cyclin D1/cdk4 and cyclin B1/cdk1, as exemplified by loss of
      cyclin D1, inhibition of specific Rb phosphorylation (pRb-p at Thr821), and by
      the time- and dose-dependent increase in the expression of NQO2. CONCLUSION: By
      exerting control on expression of specific cell cycle regulatory proteins in
      concomitance with suppression of cell proliferation, as well as the induction of
      NQO2, gamma-tocotrienol offers promise as an added chemopreventive and/or
      chemotherapeutic agent against breast cancer carcinogenesis.

PMID- 20683026
TI  - The influence of cyclin D1 A870G polymorphism on colorectal cancer risk and
      prognosis in a Turkish population.
AB  - BACKGROUND: Cyclin D1, encoded by the gene CCND1, is a regulatory protein in the
      cell cycle transition from G(1) phase to S phase. A common polymorphism (A870G)
      at codon 242 affects splicing of the CCND1 transcript and may cause
      uncontrollable cellular growth. The present study was performed to test the
      association between A870G polymorphisms in the CCND1 gene and colorectal cancer
      risk and progression. PATIENTS AND METHODS: The 870 A>G polymorphism in the
      cyclin D1 gene was genotyped in a Turkish colorectal cancer case-control
      population including fifty-seven cases (35 male, 22 female; mean age + or - SD:
      59.33 + or - 13.7 years) and 117 controls (63 male, 54 female; mean age + or -
      SD: 54.4 + or - 12.2 years) using polymerase chain reaction-restriction fragment
      length polymorphism analysis. RESULTS: Genotype frequencies of our patients and
      controls both confirmed to the Hardy-Weinberg equilibrium. There was no
      difference in the distribution of CCND1 genotypes and frequencies of the alleles
      A (59.6% versus 49.6%) and G (40.4% versus 50.4%) in the colorectal cancer
      patients and controls, respectively. Women homozygous for the cyclin D1 870 GG
      genotype showed an increased risk for developing colorectal cancer compared to
      those with the AG+AA genotypes and this result was statistically significant (OR
      5.568, 95% CI 1.270-24.417, p=0.02). On the other hand, the cyclin D1 GA genotype
      was associated with distant metastasis (p=0.016). CONCLUSION: Our findings
      suggest that genetic variants of A870G might be associated with distant
      metastasis and also gender.

PMID- 20683027
TI  - Induction of apoptosis by sphingosine, sphinganine, and C(2)-ceramide in human
      colon cancer cells, but not by C(2)-dihydroceramide.
AB  - Complex dietary sphingolipids such as sphingomyelin and glycosphingolipids have
      been reported to inhibit the development of colon cancer. This protective role
      may be the result of the conversion of complex sphingolipids to bioactive
      metabolites including sphingoid bases (sphingosine and sphinganine) and ceramide,
      which inhibit proliferation and stimulate apoptosis. In the current study, we
      evaluated the significance of the 4,5-trans double bond by comparing the effects
      of sphingosine and the cell permeable short-chain ceramide analog C(2)-ceramide
      to those of sphinganine and C(2)-dihydroceramide, which lack this structural
      feature. The effects of the sphingoid bases, C(2)-ceramide, and C(2)
      dihydroceramide on apoptosis were determined by detecting 200-bp DNA ladders or
      hypo-diploid areas (sub-G(0)/G(1)), indicative of apoptosis, in HCT-116 human
      colon cancer cells. In addition, the effects of the sphingoid bases at an
      apoptotic concentration for 12 hours on cell cycle distribution were determined
      by flow cytometry. The results indicated that the sphingoid bases and C(2)
      ceramide induced apoptosis, whereas C(2)-dihydroceramide had no effects.
      Sphingoid bases arrested the cell cycle at the G(2)/M phase. The present study
      provides evidence that the 4,5-trans double bond is necessary for the apoptotic
      effect of C(2)-ceramide, but not for that of sphingoid bases.

PMID- 20683028
TI  - Combined effect of CYP1B1 codon 432 polymorphism and N-acetyltransferase 2 slow
      acetylator phenotypes in relation to breast cancer in the Turkish population.
AB  - BACKGROUND: Breast cancer (BC), is more prevalent in subjects who have had
      prolonged exposure to heterocyclic amines, aromatic amines and high levels of
      oestradiol. Cytochrome P450 1B1 (CYP1B1) and N-acetyltransferase2 (NAT2) have
      complementary role in metabolism of xenobiotics such as arylamines and
      heterocyclic amines, CYP1B1 also hyroxylates 17-beta oestradiol. CYP1B1*3
      polymorphism and seven missense and four silent polymorphisms of NAT2 were
      investigated. PATIENTS AND METHODS: Sixty Turkish female BC patients and 103
      healthy controls were phenotyped by polymerase chain reaction (PCR) based
      restriction fragment length polymorphism (RFLP). RESULTS AND CONCLUSION: The
      distribution of NAT2 activity in the healthy control group was found to be
      correlated with that of healthy caucasians. Patients had slow acetylator
      phenotypes of NAT2, 1.8 times higher than controls but no statistical differences
      were found (p=0.07). In addition, the NAT2*5 alelle was more statistically
      correlated with breast cancer patients rather than the controls (p=0.02).
      Moreover, NAT2*5B was the most frequent haplotype of the NAT2*5 family (p=0.000).
      Breast cancer patients were detected to posses more CYP1B1*3 mutant alleles than
      the controls (p=0.043). The combined effect of CYP1B1*3 polymorphism and NAT2
      slow acetylator genotype contributed to an increased risk for breast cancer in
      patients in this study (p=0.004).

PMID- 20683029
TI  - The efficacy of imiquimod on dysplastic lesions of the oral mucosa: an
      experimental model.
AB  - AIM: To study the potent efficacy of the immunomodulatory agent imiquimod when
      applied on dysplastic lesions of the oral mucosa. MATERIALS AND METHODS:
      Carcinogen (DMBA) was applied to the mucosa of the left buccal pouch of 26 male
      Wistar rats for 8 weeks, until dysplastic lesions were observed and
      histologically diagnosed. At the second phase of the experiment, 5% imiquimod
      cream was applied to these dysplastic lesions for 16 weeks. Biopsies were taken
      before and after treatment. RESULTS: The histological effect of imiquimod was the
      regression of mild dysplasia to hyperplasia for all the samples. In one case, a
      well-differentiated squamous cell carcinoma was converted to a papilloma-like
      squamous neoplasm with a benign morphology. CONCLUSION: Our results indicate that
      imiquimod may be effective in treatment of precancerous lesions of the oral
      mucosa and thus inhibit the progress of carcinogenesis.

PMID- 20683030
TI  - Estrogen receptors alpha and beta immunohistochemical expression:
      clinicopathological correlations in pituitary adenomas.
AB  - AIM: We investigated the immunohistochemical expression of estrogen receptors
      alpha (ERalpha) and beta (ERbeta) in pituitary adenoma subtypes combined with
      clinicopathological factors. MATERIALS AND METHODS: Pituitary adenomas (n=75)
      were immunostained for ERalpha and ERbeta using the streptavidin-biotin
      peroxidase complex method with a monoclonal ERalpha antibody and polyclonal
      ERbeta antibody. RESULTS: Nuclear immunoreactivity for both receptors was highest
      among PRL, FSH/LH, null cell, and GH adenomas. ACTH, silent subtypes I and II
      corticotrophs, and subtype III adenomas were the least immunoreactive for both
      receptors. ACTH adenomas expressed significantly less ERalpha than FSH-LH, GH,
      and null cell adenomas. A significantly elevated ERalpha expression was observed
      in macroadenomas compared to microadenomas and non-invasive compared to invasive
      tumors. CONCLUSION: ERalpha and ERbeta are differentially expressed in the
      various pituitary adenoma subtypes suggesting a cell-specific function for these
      receptors. To elucidate the role of ERalpha in tumor size and invasiveness,
      additional studies are required.

PMID- 20683031
TI  - Docetaxel second-line therapy in patients with advanced pancreatic cancer: a
      retrospective study.
AB  - BACKGROUND: No therapeutic standard of care exists for patients who have
      progressed following first-line treatment with a gemcitabine-based regimen with
      advanced pancreatic cancer. Approximately half of the patients failing upfront
      treatment present with ECOG PS 1-2 and are willing to undergo further treatment.
      Docetaxel activity against pancreatic cancer is reported both in the preclinical
      and clinical setting. This study retrospectively evaluated the role of docetaxel
      as second-line therapy in patients with gemcitabine-refractory disease. PATIENTS
      AND METHODS: Between January 2006 and November 2009, 17 patients (median age of
      61 years) with advanced pancreatic adenocarcinoma, after receiving gemcitabine
      containing chemotherapy as first-line median ECOG performance status 1 and with
      adequate organ function, were treated with either weekly docetaxel at 25 mg/m(2)
      or 3-weekly docetaxel regimen (docetaxel at 75 mg/m(2) or docetaxel-gemcitabine
      capecitabine or docetaxel-gemcitabine) until progressive disease. Serum CA19-9
      levels were measured every 3/4 weeks and CT scans performed after every
      eight/nine weeks. RESULTS: Docetaxel dose intensity was 90% in the patients who
      received weekly docetaxel, 85% in docetaxel-erlotinib regimen and 65% in 3-weekly
      regimen (docetaxel-gemcitabine-capecitabine, docetaxel-gemcitabine). Only one
      objective response (6%) to treatment was obtained (docetaxel-gemcitabine), while
      5 patients achieved stable disease (weekly docetaxel). Median progression-free
      survival was 8 weeks (range: 3-16 weeks) and median survival was 4.0 months
      (range: 2.0-6.5 months). No toxicity with grade >3 associated with docetaxel was
      observed. CONCLUSION: Docetaxel seems to have mild activity in the treatment of
      gemcitabine-resistant metastatic pancreatic cancer. Although some patients may
      benefit from the treatment, other dosing regimens and novel taxanes such as Nab
      paclitaxel should be explored in this setting.

PMID- 20683032
TI  - Levels of elevated circulating endothelial cell decline after tumor resection in
      patients with pancreatic ductal adenocarcinoma.
AB  - AIM: To evaluate circulating endothelial lineage cells (ELCs) as biomarkers of
      tumor neovascularization in patients with pancreatic ductal adenocarcinoma
      (PDAC). MATERIALS AND METHODS: ELCs were isolated from the peripheral blood of
      patients with PDAC (n=14) or controls (n=17) before and after tumor
      resection/surgery and quantified using flow cytometry. Vascular endothelial
      growth factor (VEGF) and placental growth factor (PlGF) were detected in tumor
      using immunohistochemistry and in plasma using an ELISA technique. RESULTS:
      Circulating ELC levels were increased in patients with PDAC compared to controls.
      After PDAC resection, ELC levels declined. ELC level increases were associated
      with cancer recurrence. VEGF and PlGF were identified in cancer cells and
      exocrine pancreas cells. Only PlGF was detected in tumor-associated inflammatory
      cells. Plasma levels of PlGF were higher in patients with PDAC compared to
      controls. CONCLUSION: Circulating ELCs are a potential biomarker of PDAC
      neovascularization, and PlGF may be an important target in treatment of PDAC.

PMID- 20683033
TI  - Zinc-alpha2-glycoprotein: a new biomarker of breast cancer?
AB  - BACKGROUND/AIM: Obesity increases the risk of breast cancer. It is established
      that adipocyte secretions, i.e. adipokines, may play a role in mammary
      carcinogenesis. We have shown that two major adipokines, leptin and adiponectin,
      were expressed in mammary adenocarcinoma. PATIENTS AND METHODS: Here, we
      evaluated zinc-alpha2-glycoprotein (ZAG) expression in tumor (n=55) and healthy
      (n=6) breast tissue by immunohistochemistry and examined whether it was
      correlated with that of major adipokines, usual tumor biomarkers (sex steroids
      receptors, i.e. estrogen (ER) and progesterone; Ki-67; cErb2), or apoptosis
      markers (Bcl2 and Bax). RESULTS: ZAG expression was detected in ductal carcinoma
      and normal epithelial adjacent tissue but not in normal tissue of healthy women.
      In cancer tissue, its expression was correlated positively to leptin receptor and
      negatively to adiponectin receptor and ER. CONCLUSION: These preliminary results
      suggest both a relationship between ZAG expression and pathways involving
      adipokines or estrogen and that ZAG may be a potential breast cancer biomarker.

PMID- 20683034
TI  - Role of pregabalin in treatment of oxaliplatin-induced sensory neuropathy.
AB  - BACKGROUND: Oxaliplatin use in gastrointestinal malignancies is limited by
      neurotoxicity. This study aimed to assess the efficacy of pregabalin (LYRICA(R))
      in the treatment of oxaliplatin-induced neurotoxicity. PATIENTS AND METHODS: A
      total of 23 gastrointestinal cancer patients with grade 2 and 3 oxaliplatin
      induced sensory neuropathy were treated with pregabalin up to a target dose of
      150mg orally (PO) three times a day (tid) based on benefit and tolerance.
      Neurological symptoms were serially evaluated. RESULTS: The target dose of 150 mg
      tid provided the best benefit, but patients benefited even at lower doses. Onset
      of benefit was observed in 2-6 weeks. In the majority of patients (48%),
      neuropathy improved by 1 to 2 grades. CONCLUSION: Pregabalin significantly
      reduced the severity of oxaliplatin-induced sensory neuropathy. Being more potent
      than gabapentin, pregabalin achieved efficacy at lower doses and should lead to
      fewer dose-related side effects, although this remains to be established in a
      head-to-head trial.

PMID- 20683035
TI  - Effects of the Src inhibitor saracatinib (AZD0530) on renal function in healthy
      subjects.
AB  - BACKGROUND: Saracatinib (AZD0530), a potent Src inhibitor, is a subject of
      current evaluation as an anticancer therapy. Increased plasma creatinine levels
      have previously been observed after saracatinib administration in healthy
      subjects and this study was undertaken to characterize the underlying mechanism
      of this increase. SUBJECTS AND METHODS: 56 healthy male subjects were assigned to
      either single- (n=28; randomised to placebo or saracatinib 500 mg) or multiple
      dose oral treatment (n=28; randomised to placebo or saracatinib 125 mg for 14
      days). Renal function variables assessed included inulin clearance and tubular
      secretion of creatinine. RESULTS: Saracatinib led to a reduction in mean
      creatinine fractional excretion ratio, which was due to a reduction in tubular
      secretion of creatinine. Increased plasma creatinine was not associated with
      decreased glomerular filtration rate or increased creatinine production.
      CONCLUSION: The observed increase in plasma creatinine after saracatinib
      administration was due to reduced tubular secretion of creatinine, but was not
      considered to be clinically relevant in the context of this study.

PMID- 20683036
TI  - Validation of blood testing for K-ras mutations in colorectal and pancreatic
      cancer.
AB  - BACKGROUND: K-ras mutation in a tumour is a powerful negative predictor for
      treatment success. Identifying tumour K-ras mutation is complex, and could be
      simplified by an appropriate blood test. Clinical studies were identified in
      which K-ras mutation status was assessed in both blood and tumour to ascertain
      whether blood K-ras mutation is predictive of tumour K-ras mutation. Between 29%
      and 100% of patients with a tumour K-ras mutation in 11 studies presented the
      same mutation in peripheral blood. Only 5/272 patients presented blood K-ras
      mutation in the absence of the same tumour mutation, possibly due to sampling
      errors. K-ras mutation in blood appears to indicate K-ras mutation in tumour,
      while the absence of blood K-ras mutation does not prove lack of mutation in the
      tumour. This suggests that a blood test for the detection of tumour K-ras may be
      possible, and could direct cancer treatment strategies.

PMID- 20683037
TI  - A 'hot' leg: a rare case of isolated long bone metastases from cervical cancer.
AB  - A 70-year-old woman with a past medical history of FIGO stage IIIA cervical
      cancer presented with severe pain in her right leg and after investigations was
      found to have isolated metastases within the right tibia, fibula and calcanuem.
      Bone metastases from cervical cancer are relatively rare and tend to occur in the
      spine and pelvis. There are only a handful of case reports of isolated long bone
      metastases from cervical cancer in the literature. This case highlights the
      importance of diagnostic imaging and the role of histological confirmation when
      there is diagnostic uncertainty.

PMID- 20683038
TI  - Soluble carbonic anhydrase IX is not an independent prognostic factor in human
      renal cell carcinoma.
AB  - The aim of this study was to evaluate the prognostic information of soluble
      carbonic anhydrase (CA) IX expression in renal cell carcinoma (RCC). PATIENTS AND
      METHODS: Serum CA IX was analysed in 361 patients. Tumour type, TNM stage,
      nuclear grade, and RCC-specific survival were assessed. Serum and
      immunohistochemical expression were compared. RESULTS: Median serum CA IX
      expression was 141 (range 2-4, 181) pg/ml. Levels were significantly higher in
      287 patients with clear cell, compared to 40 papillary (p<0.001) and 22
      oncocytoma (p=0.002), but not to 12 chromophobe RCC (p=0.35). Serum CA IX in
      clear cell RCC was positively correlated to TNM stage (p=0.002). There was a
      positive trend between serum and immunohistochemical CA IX expression. In a
      multivariate analysis of clear cell RCC, TNM stage and nuclear grade were
      independent prognostic factors. CONCLUSION: Serum CA IX was higher in clear cell
      RCC compared to other RCC types. In clear cell RCC, serum CA IX correlated to TNM
      stage, but not survival.

PMID- 20683039
TI  - Postoperative external beam radiotherapy for resected pancreatic adenocarcinoma:
      impact of chemotherapy on local control and survival.
AB  - AIM: To analyze retrospectively the results of postoperative external beam
      radiotherapy (EBRT) for resected pancreatic adenocarcinoma. PATIENTS AND METHODS:
      The records of 47 patients treated with gross complete resection (R0: 24
      patients, R1: 23 patients) and post-operative EBRT were reviewed. The median dose
      of EBRT was 50 Gy (range, 12-60 Gy), and chemotherapy was used in 37 patients
      (78.7%). The median follow-up period for all 47 patients was 14.4 months (range,
      0.9-67.9 months). RESULTS: At the time of this analysis, 24 patients (51.1%) had
      disease recurrence. Local failure was observed in 10 patients (21.3%), and the 2
      year local control (LC) rate in all patients was 68.7%. Patients treated with
      EBRT and chemotherapy had a significantly more favorable LC (2-year LC rate:
      76.0%) than those treated with EBRT alone (2-year LC rate: 40%, p=0.0472). The
      median survival time and the 2-year actuarial overall survival (OS) in all 47
      patients were 30.0 months and 54.5%, respectively. Patients treated with EBRT and
      chemotherapy had a significantly more favorable OS (2-year OS rate: 61.6%) than
      those treated with EBRT alone (2-year OS: 25.0%, p=0.0454). On univariate
      analysis, chemotherapy use alone had a significant impact on OS, and on
      multivariate analysis, chemotherapy use also was a significant prognostic factor.
      There were no late morbidities of NCI-CTC Grade 3 or greater. CONCLUSION: Post
      operative EBRT with chemotherapy yields a favorable LC rate for resected
      pancreatic adenocarcionoma, and EBRT combined with chemotherapy confers a
      survival benefit compared to EBRT alone.

PMID- 20683040
TI  - Bevacizumab combined with two-weekly paclitaxel as first-line therapy for
      metastatic breast cancer.
AB  - BACKGROUND: Metastatic breast cancer remains a major clinical issue despite
      progress achieved in recent years. Three randomised trials have demonstrated the
      benefit of combining bevacizumab with various taxane schedules. Herein, this
      study sought to investigate an alternative bevacizumab-taxane regimen as first
      line treatment for metastatic breast cancer. PATIENTS AND METHODS: Patients with
      metastatic breast cancer and who received first-line bevacizumab 10 mg/kg with
      paclitaxel 135 mg/m(2) every 2 weeks were studied. RESULTS: All 43 enrolled
      patients were evaluable for efficacy and safety. The response rate was 58%; a
      further 40% achieved stable disease. After a median follow-up of 16 months,
      disease had progressed in 9 patients (21%). Treatment was well tolerated: grade 4
      toxicities were absent; grade 3 adverse events comprised neutropenia (5%; no
      febrile neutropenia), hypertension (2%) and neuropathy (2%). CONCLUSION: This
      regimen may provide improved patient acceptability, quality of life and
      pharmacoeconomic benefits over a weekly paclitaxel schedule, and deserves further
      evaluation.

PMID- 20683041
TI  - Prognostic value of lymphovascular invasion in bladder cancer in patients treated
      with radical cystectomy.
AB  - BACKGROUND: Bladder cancer is the fourth most frequently diagnosed cancer among
      males and the eleventh among females. At present, radical cystectomy is
      considered the standard therapy in patients with muscle invasive disease or in
      some cases of high-grade superficial cancer. TNM classification includes as
      independent predictors of disease-specific survival the grade, the pathological
      stage and the presence of lymph node involvement, whilst the prognostic value of
      lymphovascular invasion (LVI) still remains controversial. The aim of the study
      was to assess the prognostic role of LVI at final pathology. PATIENTS AND
      METHODS: From June 1995 to January 2007, 340 consecutive patients underwent
      radical cystectomy. Surgical specimens were examined according to our
      pathological protocol. Patients with a non-transitional cell carcinoma or
      submitted to a salvage procedure or neoadjuvant/adjuvant chemo-radiotherapy were
      excluded. The follow-up consisted of abdominal ultrasound every 3 months, blood
      sampling every six months and both computerized tomography and urethroscopy
      yearly. RESULTS: The median patient age was 69 years. Of the 265 patients, 218
      were males and 47 females. LVI was present in 77 pathological specimens (29.1%).
      LVI was not significantly associated with age (p=0.908) or sex (p=0.382), but was
      significantly associated with high pathological grade (p=0.028) and stage
      (p<0.001), and the presence of node metastasis (p<0.001). At the multivariate
      analysis, pathological staging, presence of LVI and node metastasis were
      independent significant prognostic factors for disease-specific survival.
      CONCLUSION: In our series, LVI is an independent prognostic factor for disease
      specific survival in patients who underwent radical cystectomy for transitional
      cell carcinoma.

PMID- 20683042
TI  - Influence on Busilvex pharmacokinetics of clonazepam compared to previous
      phenytoin historical data.
AB  - This study investigated the effect of seizure prophylaxis on busulfan (Bu) plasma
      exposure. Twenty-four adult patients received an intravenous Bu-cyclophoshamide
      conditioning regimen prior to bone marrow transplantation. Busilvex (0.8 mg/kg)
      was administered every six hours during four consecutive days. Clonazepam (0.025
      to 0.03 mg/kg/day as a continuous 12-h i.v. infusion) was administered at least
      12 hours prior to i.v. Bu dosing and continued until 24 hours after the last
      dose. Pharmacokinetic (PK) data were compared with those previously collected in
      patients (n=127) treated with phenytoin for seizure prophylaxis. Through
      population PK analysis, a 10% average increase (coefficient of variation,
      RSE=5.35%) in total clearance of Bu was quantified when Bu was associated with
      clonazepam as compared to phenytoin, which was considered as not being clinically
      relevant. The suspected induction on Bu metabolism by phenytoin should have
      resulted in the opposite effect. The patient efficacy and safety profiles were
      comparable between the two cohorts.

PMID- 20683043
TI  - Pooled analysis of S-1 trials in non-small cell lung cancer according to
      histological type.
AB  - BACKGROUND: The antimetabolic agent S-1 inhibits thymidylate synthase similar to
      pemetrexed, but through a different mechanism of action. Whether the antitumour
      activity of S-1 depends on histological type remains unclear. We analysed pooled
      data from 2 phase II clinical studies of cisplatin and S-1 in patients with
      previously untreated advanced non-small cell lung cancer. PATIENTS AND METHODS:
      We comprised 110 patients with stage IIIB or IV non-small cell lung cancer.
      Univariate and multivariate analyses were performed to determine the effects of
      histological type on progression-free survival and response rates. RESULTS: On
      pooled analysis of the data, according to histological type, median progression
      free survival was 3.8 months in patients with squamous cell carcinoma and 4.4
      months in those with non-squamous cell carcinoma. Both analyses showed that
      progression-free survival and response rate did not differ significantly.
      CONCLUSION: Unlike molecular targeted agents and pemetrexed, a combination of
      cisplatin and S-1 may be no difference in response according to histological
      type.

PMID- 20683044
TI  - Cervical manifestation of a borderline type ovarian cancer with pseudomyxoma
      peritonei - a case report.
AB  - Borderline tumours of the ovary (BOTs) are rare tumour entities that do not show
      any destructive or invasive growth in the majority of cases, even though they can
      display characteristics of malignant tumours The mucinous subtype can also
      originate from the appendix, and ovarian metastases can mimic primary ovarian
      BOTs, often accompanied by peritoneal manifestation in terms of pseudomyxoma
      peritonei. In cases where a concomitant appendiceal tumour is present, it may
      prove difficult to determine the primary tumour. This report describes a special
      case of BOT with a specific example of the complexity of the differential
      diagnosis of pseudomyxoma peritonei. Especially the case was simultaneously
      linked to appendiceal and ovarian cancer. Moreover, this case was exceptional for
      its unusual manifestation of BOT in the cervix.

PMID- 20683045
TI  - Immunohistochemical study of claudin 18 involvement in intestinal differentiation
      during the progression of intraductal papillary mucinous neoplasm.
AB  - BACKGROUND AND AIM: A comparison was made between pancreatic ductal
      adenocarcinoma (PDAC), pancreatic intraepithelial neoplasia (PanIN) and
      intraductal papillary mucinous carcinoma (IPMC) in order to understand the
      association between several markers and malignant potential. PATIENTS AND
      METHODS: Fifteen surgically resected PDACs and four IPMCs were subjected to
      immunohistochemistry with primary antibodies to Ki-67, p53, MUC2, Gli-1, and
      Claudin-18 (CLDN18). RESULTS: Ki-67, P53, MUC2, Gli-1 and CLDN18 were positive in
      6 (50%), 10 (66.6%), 0 (0%), 4 (26.6%), and 6 (40%) of the 15 PDACs,
      respectively. Low- to high-grade PanIN complexes were found in 2 out of the 15
      PDACs. Gli-1 was continuously expressed in low- and high-grade PanINs. CLDN18 was
      specifically expressed in high-grade PanINs, whereas the corresponding invasive
      tubules did not express CLDN18. P53 was positively stained in one of the 4 IPMCs
      in which minimally invasive tubular type carcinomas were observed. Ki-67 and
      CLDN18 were positively stained in all 4 IPMCs. CLDN18 was specifically expressed
      in intestinal-type components of IPMCs. CONCLUSION: CLDN18 is involved in
      intestinal-type epithelial differentiation in the progression of IPMCs,
      contradicting the previous knowledge of its specificity in gastric epithelial
      differentiation.

PMID- 20683046
TI  - Successful right hepatectomy after four treatments of yttrium-90 microspheres
      (SIR-Spheres) and concomitant FOLFOX as bridging therapy to resection of
      colorectal liver metastases.
AB  - The use of yttrium-90 microspheres is a novel interventional radiological
      procedure that has delivered promising results in the treatment of liver cancer.
      Multiple treatments in combination with systemic chemotherapy may be realised as
      an effective modality for unresectable colorectal liver metastases. This case
      study reports the first case of a patient who had a complete response of 7 out of
      10 liver metastases following multiple doses of yttrium-90 microsphere therapy,
      who then underwent a curative hepatic resection. This case demonstrates the
      feasibility and potential use of this management strategy to expand the role of
      successful therapies that will bridge the road towards curative liver resection.

PMID- 20683047
TI  - Amyloid deposition in the tongue: clinical and histopathological profile.
AB  - AIMS: Oral amyloidosis is a rare and debilitating disease that, whether primary
      or secondary, may severely impact the quality of a patient's life. The study
      investigated the characteristics of amyloid deposition in the tongue from the
      clinical and histopathological profiles. MATERIALS AND METHODS: Biopsy specimens
      were received from five patients: 2 female, 3 male. All biopsies were taken from
      the tongue, and all had amyloid deposition in the subepithelial connective
      tissue, conclusive for a diagnosis of amyloidosis. All patients showed
      macroglossia and difficulty in eating and impairment of speech. RESULTS: In three
      cases there was no evidence of systemic involvement or associated disease; these
      were characterized as localized amyloidosis of the tongue. The other two cases
      revealed multisystemic involvement. Histologically, the disease was diagnosed
      through specific staining with Congo red, which examined under polarized light
      revealed the amyloid deposits as apple-green birefringence. CONCLUSION: The
      findings show the tongue to be the site most frequently affected in forms of
      localised amyloidosis, and that a tongue biopsy possess a highly diagnostic value
      for amyloidosis. There is still no consensus regarding the management of lingual
      amyloidosis, although numerous therapies have been proposed, including surgical
      excision and pharmacological treatment. However lesions often persist or recur.
      The prognosis is uncertain, owing to the rarity of the condition, requiring
      regular follow-up and monitoring.

PMID- 20683048
TI  - Metastatic breast cancer presenting as a primary hindgut neuroendocrine tumour.
AB  - The examination of limited, potentially non-representative fragments of tumour
      tissue from a core biopsy can be misleading and misdirect subsequent treatment,
      especially in cases where a primary tumour has not been identified. This case
      report is of a 65-year-old woman presenting with a destructive sacral mass,
      diagnosed on radiological imaging and core biopsy as a hindgut neuroendocrine
      tumour, which on histopathological review of the subsequently resected tumour was
      found instead to represent a metastasis from an occult hormone-positive breast
      cancer with neuroendocrine features.

PMID- 20683049
TI  - Protruding and non-protruding colon carcinomas originating in gut-associated
      lymphoid tissue.
AB  - BACKGROUND: Colon carcinomas arising in gut-associated lymphoid tissue (GALTC)
      are termed dome carcinomas (DC) because of their protruding phenotype. Only 8
      GALTC cases have been reported in the literature. CASE REPORT: A female patient,
      aged 53, having a familial pedigree of colon cancer, uterine cervix cancer and
      brain tumour developed a signet-ring carcinoma in the cecum and 10 years later
      endometrial cancer. While asymptomatic, a plaque-like protrusion in the colon was
      detected at surveillance colonoscopy. Histology demonstrated a protruding GALTC.
      The surgical specimen showed four additional carcinomas: 2 GALTC (non-protruding)
      and 2 carcinomas in lymphoid-free colonic mucosa (LFCMC). CONCLUSION: Since
      adenomas could not be demonstrated neither previously nor in the colectomy
      specimen, it is suggested that the GALTCs in this patient may have followed the
      GALT-carcinoma pathway.

PMID- 20683050
TI  - Prognostic evaluation of COX-2 expression in renal cell carcinoma.
AB  - BACKGROUND: Prognosis of renal cell carcinoma (RCC) differs within the same stage
      and grade. Our aim was to investigate the incidence of COX-2 in primary RCC
      tumors at different stages according to the occurrence of metastasis, and the
      impact of this biomarker on the survival of RCC patients. PATIENTS AND METHODS:
      The cytoplasmic/membranous COX-2 protein expression was examined by
      immunohistochemistry in RCC tumors from 102 patients. The patients were divided
      into those with: no metastasis during 7.5 years' follow-up (nm), no metastasis at
      the time of nephrectomy but who later developed metastases (lm), and those with
      metastasis at presentation (pm). The immunoreactivity of COX-2 was classified as
      none (absent/weak intensity in fewer than 10% of the cancer cells), low (weak
      intensity in over 10% of the cancer cells) or high immunostaining (strong
      intensity in the majority of the cancer cells). In addition p53 and Ki-67
      immunostaining was also assessed in tumors. RESULTS: Percentages of COX-2
      reaction were (no/low/high): 78/16/7 in the nm, 53/28/19 in the lm, 92/8/0 in the
      pm groups (p=0.014). Median metastasis-free survival was shorter in lm patients
      with COX-2-negative tumors when compared to those with COX-2-positive ones (15
      vs. 46 months; p=0.020). Median overall survival was shorter in pm/lm patients
      with COX-2-negative tumors when compared to those with COX-2-positive ones (28
      vs. 94 months; p=0.027), and with COX-2-negative/Ki-67-positive tumors when
      compared to COX-2-positive/Ki-67-negative ones (19 vs. 97 months; p=0.004).
      Findings for patients with COX-2-negative/p53-positive tumors were similar, with
      shorter survival compared to those with COX-2-positive/p53-negative ones (19 vs.
      97; p=0.006). CONCLUSION: COX-2 protein expression is associated with slow
      development of metastases, and favourable prognosis in metastatic RCC.

PMID- 20683051
TI  - Phase III study comparing sequential versus alternate administration of cisplatin
      etoposide and topotecan as first-line treatment in small cell lung cancer.
AB  - AIM: To compare the efficacy and tolerance of sequential versus alternate front
      line administration of cisplatin-etoposide (PE) and topotecan (T) in patients
      with extensive stage small cell lung cancer (SCLC). PATIENTS AND METHODS:
      Patients were randomized to receive either 4 cycles PE (cisplatin 80 mg/m(2) i.v.
      day 1 and etoposide100 mg/m(2)/d i.v. days 1-3 every 21 days) followed by 4
      cycles T (1.5 mg/m(2)/d i.v. days 1-5 every 21 days) (arm A, 183 patients) or the
      same regimens using an alternate sequence (arm B, 181 patients). RESULTS: There
      was no significant difference in terms of compliance with treatment, overall
      response rates (51.4% vs. 55.2%; p=0.458), median response duration (4.3 vs. 5.2
      months; p=0.780), median time to tumour progression (5.7 vs. 6.4 months;
      p=0.494), median overall survival (10.9 vs. 9.8 months; p=0.186) and 1-year
      survival (43.8% vs. 36.5%) between the two arms. The incidence of severe grade 3
      4 haematological and grade 2-4 non-haematological (asthenia, mucositis, diarrhoea
      and neurotoxicity) toxicity was comparable between the two arms. CONCLUSION: The
      comparison of sequential versus alternate administration of cisplatin-etoposide
      and topotecan as front-line treatment of patients with extensive stage SCLC
      revealed no clinically meaningful differences in terms of efficacy and tolerance.

PMID- 20683052
TI  - Phase II trial of adjuvant chemotherapy with bi-weekly carboplatin plus
      paclitaxel in patients with completely resected non-small cell lung cancer.
AB  - BACKGROUND: Adjuvant chemotherapy improves the prognosis of patients with non
      small cell lung cancer (NSCLC) after a complete resection despite unacceptable
      toxicity and low compliance. METHODS: A total of 67 patients were enrolled in a
      multi-institutional study. The patients received chemotherapy with carboplatin
      (CBDCA) area under the curve of 3 and paclitaxel (PTX) 90 mg/m(2) every 2 weeks
      for six cycles after surgery. RESULTS: Fifty patients (74.6%) completed all
      cycles of therapy. The presence of grade 3 and 4 toxicities of neutropenia were
      13.4, and 3.0%, respectively. Non-haematological adverse effects were infrequent
      and no treatment-related death was registered. The estimated disease-free
      survival and overall survival at 2 years were 89.0% and 88.8%, respectively.
      CONCLUSION: A bi-weekly schedule of CBDCA and PTX as adjuvant chemotherapy showed
      an acceptable toxicity and favourable feasibility in Japanese NSCLC patients
      after complete tumor resection. Consequently, it is desirable to validate this
      regimen in a future randomized clinical trial.

PMID- 20683053
TI  - Hepatic arterial infusion with oxaliplatin, irinotecan and doxifluridine for
      unresectable liver metastases of colorectal cancer.
AB  - AIM: To evaluate the therapeutic efficacy and safety of combination chemotherapy
      with oxaliplatin, irinotecan and doxifluridine through hepatic arterial infusion
      (HAI) in patients with unresectable liver metastases of colorectal cancer.
      PATIENTS AND METHODS: Individual patients were treated through the tumour-blood
      supplying arteries with oxaliplatin, irinotecan and doxifluridine and
      chemoembolised with irinotecan and lipiodol for the detected hypervascular
      lesions. RESULTS: A total of 173 cumulative cycles of chemotherapy were performed
      for the 32 patients, with a median of 5.0 cycles, including 96
      chemoembolisations. Fifteen patients reached partial remission, 14 patients had
      stable disease and only 3 patients had progressive disease. The overall response
      rate was 46.9%. Of the 32 patients, 18 patients received first-line treatment
      with an overall response rate of 61.1%. The remaining 14 patients received second
      line treatment, with an overall response rate of 28.6%. CONCLUSION: Combination
      chemotherapy through HAI is well tolerated and highly effective in patients with
      unresectable liver metastases of colorectal cancer.

PMID- 20683054
TI  - Trastuzumab plus capecitabine and docetaxel as first-line therapy for HER2
      positive metastatic breast cancer: phase II results.
AB  - In human epidermal growth factor 2 (HER-2)-positive advanced breast cancer,
      taxanes plus trastuzumab are among the most widely applied options in the first
      line setting. The addition of capecitabine to docetaxel significantly improves
      overall survival in anthracycline-pretreated metastatic breast cancer. We
      evaluated the efficacy and tolerability of trastuzumab plus capecitabine and
      docetaxel regimen as first-line therapy. PATIENTS AND METHODS: HER-2-positive
      patients who had received adjuvant anthracyclines received docetaxel at 75
      mg/m(2) on day 1 and capecitabine 950 mg/m(2)/day, days 1-14, every 3 weeks until
      disease progression or unacceptable toxicity. Trastuzumab was administered at a
      dose of 6 mg/kg every 3 weeks. Time to progression (TTP) was defined as the
      primary end point. RESULTS: Twenty-nine patients were evaluable (median age 52,
      range 34-70 years). The regimen achieved objective responses in 11 patients
      (38%), including complete response in three (10.3%) and partial response in eight
      (27.5%). The median overall survival time was 25.5 months, and the median
      progression-free survival time was 7.8 months. The safety profile of the
      combination was favorable and predictable, with a low incidence of grade 3/4
      adverse events. The most common adverse events were hand-foot syndrome, and
      gastrointestinal toxicities. Severe myelosuppression was rare and cardiac
      toxicity did not occur. CONCLUSION: These data confirm that the combination of
      trastuzumab plus capecitabine and docetaxel is highly active in patients with HER
      2-overexpressing anthracycline-pretreated breast cancer, offering a significant
      survival benefit and is well tolerated.

PMID- 20683055
TI  - Stereotactic radiosurgery plus whole-brain radiotherapy for treatment of multiple
      metastases from non-small cell lung cancer.
AB  - BACKGROUND: The aim of this study was to evaluate local control and survival
      rates after stereotactic radiosurgery (SRS) plus whole-brain radiotherapy (WBRT)
      for the treatment of multiple brain metastases from non-small cell lung cancer
      (NSCLC). PATIENTS AND METHODS: Between June 2004 and September 2008, sixty-six
      patients with multiple brain metastases from NSCLC were enrolled in this
      prospective study. All patients were required to have 2-3 brain metastases and
      Karnofsky performance status (KPS) > or = 70. WBRT treatment dose was 30 Gy in 10
      fractions followed by SRS. A matched control population treated with WBRT alone
      to a dose of 30 Gy in 10 fractions was used for comparison. RESULTS: The median
      survival was 10.3 months in the WBRT plus SRS group and 7.2 months in the WBRT
      group (p=0.005). The 6-month and 12-month survival rates were 90% and 38% in the
      SRS plus WBRT group and 84% and 19% in the WBRT group (p=0.01). Stable
      extracranial disease and KPS were significant predictive factors of survival in
      both groups (p=0.001). Death due to neurological causes occurred in 18% and 35%
      of patients treated with WBRT plus SRS and WBRT (p=0.02), respectively. Disease
      control in the brain was 10 months in the SRS plus WBRT group and 7 months in the
      WBRT group (p=0.001); the 6-month and 12-month control rates were 82% and 42% for
      WBRT plus SRS, and 75% and 18% for WBRT (p=0.001), respectively. The 6-month and
      12-month control rates of treated lesions (local control) were 90% and 47% in the
      WBRT group, and 100% and 93% in the WBRT plus SRS group (p=0.001). CONCLUSION:
      WBRT plus SRS is a safe, minimally invasive and well-tolerated treatment for
      patients with up to three brain metastases from NSCLC. The treatment is
      associated with longer survival and better disease control in comparison with
      WBRT alone. Survival benefits need to be confirmed by large randomized studies.

PMID- 20683056
TI  - Clinicopathological features in N0 oesophageal cancer patients.
AB  - BACKGROUND: The prognosis for patients with N0 oesophageal cancer is favourable,
      but relevant prognostic factors and appropriate surveillance protocols have not
      been identified for these patients. PATIENTS AND METHODS: A total of 210
      oesophageal cancer patients were included in this study. Of these, 92 (43.8%) had
      no lymph node metastasis. Predictive factors for lymph node metastasis were
      evaluated in N0 oesophageal cancer. Survival, prognostic factors, causes of death
      and pattern of recurrence were assessed between patients with and without lymph
      node metastasis. RESULTS: Logistic regression analysis revealed that depth of
      tumour invasion (T1) was an independent predictive factor for N0. The Cox
      proportional hazard regression model showed that venous invasion was an
      independent prognostic factor for disease-specific survival in N0 oesophageal
      cancer patients (hazard ratio=3.977, p=0.042). Locoregional recurrence was less
      frequent in patients with N0 oesophageal cancer (p=0.0319). CONCLUSION:
      Meticulous and long-term follow-up is necessary even for patients with N0
      oesophageal cancer, particularly for those with adverse prognostic factors.

PMID- 20683057
TI  - Does a new ultrasound probe change the complication rates of transrectal
      ultrasound-guided needle biopsies of the prostate?
AB  - BACKGROUND: Transrectal ultrasound-guided prostate needle biopsies are performed
      to diagnose prostate cancer. This study prospectively evaluated the safety,
      morbidity and complication rates with two different ultrasound probes. PATIENTS
      AND METHODS: Three huntred and thirty-two patients were biopsied using a biplane
      7.5 MHz probe (GE Medical Systems Kretz Ultrasound, Zipf, Austria) and 101
      patients using a biplane 5-10 MHz probe (BK-Medical, Herlev, Denmark). Four weeks
      after the procedure the patients were asked to fill out a questionnaire. RESULTS:
      There were 3 major and 75 minor complications. The most common complication was
      haematuria in 8.1% of cases, followed by pain with urination in 5.3% of cases.
      After changing the ultrasound probe, the complication rates were slightly higher,
      but no statistical difference in any of the complication rates was found between
      the two groups. CONCLUSIONS: Changing the method within the same team has no
      influence on complication rates and on prostate cancer detection rates.

PMID- 20683058
TI  - Preliminary results of tranilast treatment for patients with advanced castration
      resistant prostate cancer.
AB  - BACKGROUND: Tranilast is a therapeutic agent used in treatment of allergic
      diseases. It has been reported previously that tranilast has antitumour effects
      on prostate cancer cells. This study examined whether tranilast has clinical
      benefit for prostate cancer patients. PATIENTS AND METHODS: Twenty-one Japanese
      patients with advanced castration-resistant prostate cancer (CRPC) were
      administered tranilast orally. RESULTS: All patients had already been treated
      with combined androgen blockade followed by one or more salvage therapies and
      their prostate-specific antigen (PSA) continued to increase before starting
      tranilast. Median follow-up time was 14 months and median tranilast treatment
      time was 5 months. PSA progression was inhibited in 5 CRPC patients with bone
      metastasis. The survival rates at 12 and 24 months were 74.5% and 61.5%,
      respectively. CONCLUSION: Although this study involved only pilot data, it
      indicates that tranilast may improve the prognosis of patients with advanced
      CRPC.

PMID- 20683059
TI  - Fine-needle aspiration cytology and (99m)Tc-pertechnetate scintigraphy together
      in patients with differentiated thyroid carcinoma.
AB  - The aim of this study was to evaluate the usefulness of fine-needle aspiration
      cytology (FNAC) and (99m)Tc-pertechnetate scintigraphy (TS) together in patients
      with differentiated thyroid carcinoma. Data from a series of 357 patients (284
      women and 73 men, median age 43 years, range 19-73) with solitary thyroid nodule
      and no signs of hyperfunction, who had undergone both FNAC and TS prior to
      surgery, were retrospectively reviewed. FNAC distinguished 3 groups of TN
      (benign, follicular neoplasm, cancer), while patients with 'cold' TN were
      considered at risk of having a thyroid tumor. The sensitivity, specificity,
      positive predictive value, negative predictive value, and accuracy were: 95%,
      21%, 20%, 95% and 34% for TS; 82%, 99%, 96%, 96% and 96% for FNAC; 98%, 99%, 97%,
      98%, and 99% for TS and FNAC together, respectively. In conclusion, patients with
      'cold' TN and FNAC suggesting follicular neoplasm should be considered at risk of
      having cancer.

PMID- 20683060
TI  - Vinorelbine plus 24-hour infusion of high-dose 5-fluorouracil and leucovorin as
      effective palliative chemotherapy for breast cancer patients with acute
      disseminated intravascular coagulation.
AB  - BACKGROUND: Cancer-related acute disseminated intravascular coagulation (DIC) is
      uncommon, but it is a severe complication resulting in a very dismal prognosis.
      Choosing the appropriate chemotherapy agents to treat the underlying cancer and
      stop the acute DIC process effectively, while avoiding chemotherapy-induced
      myelosuppression which may contribute to bleeding-related mortality, is
      difficult. Acute DIC in breast cancer is a rare condition and is not well
      studied. Therefore, we designed this study to determine the clinical
      characteristics and effective treatment for breast cancer patients with acute
      DIC. PATIENTS AND METHODS: From March 1996 to November 2008, patients with
      histologically proven breast cancer who presented with acute DIC at National
      Taiwan University Hospital were retrospectively analyzed. RESULTS: Sixteen
      patients were included in the study. Thirteen patients with breast cancer-related
      acute DIC were treated with various kinds of chemotherapy, one with tamoxifen,
      and two with supportive care only. Four patients responded to treatment; three of
      the responders received vinorelbine with high-dose 5-fluorouracil and leucovorin
      (HDFL), the other received vinorelbine with cisplatin. The median survival of the
      responders and non-responders was 13 months and 0.5 month (p<0.001). There were
      no grade 3 or 4 hematologic or non-hematologic toxicities in the patients
      receiving vinorelbine-HDFL. CONCLUSION: Vinorelbine plus HDFL is considered a
      safe and effective palliative treatment of choice for breast cancer patients with
      acute DIC. Further prospective study is warranted.

PMID- 20683061
TI  - CCND1 and CDKN1B polymorphisms and risk of breast cancer.
AB  - BACKGROUND AND OBJECTIVES: Previous studies have shown alterations in the cell
      cycle regulatory proteins in breast carcinomas. However, the results of these
      studies remain controversial. Cyclin D1 (CCND1) and p27(KIP1) (CDKN1B) are two
      essential regulators of cell cycle progression. This study aimed to investigate
      the associations of CCND1 A870G and CDKN1B C79T polymorphisms with breast cancer
      risk. PATIENTS AND METHODS: Polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) was used to determine the genotype and allelic
      frequencies of polymorphisms. Seventy-eight breast cancer patients and 84 age
      matched healthy controls were included in the study. RESULTS: Frequencies of CT
      genotype and T allele of CDKN1B were found to be higher in breast cancer patients
      than in controls (p=0.013, OR: 1.514 95% CI: 1.086-2.114.15; p=0.007, OR=1.496;
      95% CI: 1.111-2.014, respectively). The frequency of AA genotype of CCND1 was
      decreased in hormone receptor- (estrogen and progesterone receptors) negative
      patients with breast cancer (p<0.049, OR=0.286; 95% CI: 0.071-1.142) CONCLUSIONS:
      Even though CDKN1B polymorphism appears to be an important predictive factor for
      breast cancer risk and CCND1 polymorphism may be a prognostic biomarker for
      breast cancer, further investigations with larger study groups are needed to
      fully elucidate the role of CCND1 and CDKN1B polymorphisms in the development and
      prognosis of breast cancer.

PMID- 20683062
TI  - Prognostic significance of tumour marker index based on preoperative CEA and
      CYFRA 21-1 in non-small cell lung cancer.
AB  - BACKGROUND: Prognostic impact of tumour marker index (TMI) based on preoperative
      serum carcinoembryonic antigen (CEA) and CYFRA 21-1 in non-small cell lung cancer
      (NSCLC) was examined using patients with a follow-up period more than 5 years.
      PATIENTS AND METHODS: Two hundred and ninety-three consecutive NSCLC patients
      were reviewed retrospectively, and any patients with follow-up periods less than
      5 years were omitted. RESULTS: The 5-year survival of the patients with normal
      and high serum CEA levels was 71.52% and 48.41%, respectively (p<0.0001). The 5
      year survival of the patients with a high serum CYFRA 21-1 level was 39.66%,
      which was significantly poorer compared with that of the patients with a normal
      serum CYFRA 21-1 level (66.95%, p<0.0001). There was a 5-year-survival rate of
      72.28% in patients with a TMI less than or equal to 1.0 compared to only 37.08%
      in patients with a TMI greater than 1.0 (p<0.0001). Both univariate and
      multivariate analyses indicated the independent prognostic impact of TMI.
      CONCLUSIONS: TMI may be useful for predicting the prognosis of NSCLC patients.

PMID- 20683064
TI  - Diabetic nephropathy: a global and growing threat.

PMID- 20683063
TI  - Xenografting of human fetal testis tissue: a new approach to study fetal testis
      development and germ cell differentiation.
AB  - BACKGROUND: Abnormal fetal testis development can result in disorders of sex
      development (DSDs) and predispose to later testicular dysgenesis syndrome (TDS)
      disorders such as testicular germ cell tumours. Studies of human fetal testis
      development are hampered by the lack of appropriate model, and intervention
      systems. We hypothesized that human fetal testis xenografts can recapitulate
      normal development. METHODS: Human fetal testes (at 9 weeks, n = 4 and 14-18
      weeks gestation, n = 6) were xenografted into male nude mice for 6 weeks, with or
      without hCG treatment of the host, and evaluated for normal cellular development
      and function using immunohistochemistry, triple immunofluorescence and
      testosterone assay. The differentiation and proliferation status of germ cells
      within xenografts was quantified and compared with age-matched controls. RESULTS:
      Xenografts showed >75% survival with normal morphology. In the first-trimester
      xenografts seminiferous cord formation was initiated and in first- and second
      trimester grafts normal functional development of Sertoli, Leydig and peritubular
      myoid cells was demonstrated using cell-specific protein markers. Grafts produced
      testosterone when hosts were treated with hCG (P = 0.004 versus control).
      Proliferation of germ cells and differentiation from gonocytes (OCT4(+)) into pre
      spermatogonia (VASA(+)) occurred in grafts and quantification showed this
      progressed comparably with age-matched ungrafted controls. CONCLUSIONS: Human
      fetal testis tissue xenografts demonstrate normal structure, function and
      development after xenografting, including normal germ cell differentiation. This
      provides an in vivo system to study normal human fetal testis development and its
      susceptibility to disruption by exogenous factors (e.g. environmental chemicals).
      This should provide mechanistic insight into the fetal origins of DSDs and TDS
      disorders.

PMID- 20683065
TI  - Prevalence of drugged drivers among non-fatal driver casualties presenting to a
      trauma centre in Hong Kong.
AB  - OBJECTIVE: To investigate the prevalence and characteristics of abusive drug
      exposure among non-fatal motor vehicle driver casualties presenting to a
      designated trauma centre in Hong Kong. DESIGN: Cross-sectional study. SETTING:
      Designated trauma centre/regional accident and emergency department in Hong Kong.
      SUBJECTS: Non-fatal motor vehicle driver casualties who presented to the trauma
      centre from 1 January 2007 to 31 December 2007. MAIN OUTCOME MEASURES: Screening
      of abusive drug exposure using commercial bedside urine immunoassay kits.
      RESULTS: Drug screening was performed in 395 injured drivers, 10% of whom tested
      positive for the drugs of interest. Ketamine was the most commonly detected
      abusive substance (found in 45% of the subjects). A significantly higher
      proportion of young drivers (aged <25 years) screened positive (odds ratio=2.3;
      95% confidence interval, 1.0-5.2; P=0.04), with the rate being 21%. The presence
      of these drugs in urine was related to the time of occurrence of the crash; those
      occurring between midnight and dawn revealed a trend towards a higher proportion
      of casualties testing drug-positive (odds ratio=2.2; 95% confidence interval, 0.9
      5.3; P=0.07). There were no significant differences in the frequency of persons
      testing positive for the screened drugs with respect to gender, class of motor
      vehicle driven, or the day of the week on which the crash occurred. CONCLUSIONS:
      The prevalence of drugged driving among non-fatal casualties in our series of
      Hong Kong drivers was 10%. The frequency of such drivers testing positive for
      drugs was significantly higher in persons aged less than 25 years. These findings
      indicate a need to amend existing laws and implement on-site drug screening for
      suspected drugged drivers.

PMID- 20683066
TI  - Phaeochromocytoma in the Hong Kong Chinese population.
AB  - OBJECTIVE: To review the clinical manifestations of phaeochromocytoma in a Hong
      Kong Chinese population. DESIGN: Retrospective review. SETTING. Five public
      hospitals in Hong Kong. PATIENTS: Seventeen patients with operated
      phaeochromocytoma between 1994 and 2003 were reviewed retrospectively. RESULTS:
      Six patients (35%) were men, 11 (65%) were women. The mean age at presentation
      was 47 (range, 17-72) years. The diagnosis post-presentation was delayed by 1 to
      132 months. Over 70% of the patients had hypertension. The most frequent symptoms
      were headache (53%), palpitations (53%), and sweating (41%); all these symptoms
      were present in 24% of the patients. Four (24%) had hereditary
      phaeochromocytoma/paraganglioma syndrome. The sensitivity of 24-hour urinary
      catecholamine measurements was 82%. Mean urinary adrenaline and noradrenaline
      concentrations were respectively 7- and 8-fold greater than the upper reference
      limits. Computed tomography and metaiodobenzylguanidine scintigraphy were the
      most widely used means for tumour localisation (sensitivity, 100% and 87%
      respectively). Approximately 65% of the patients had intra-adrenal tumours; 53%
      were on right side, 18% were bilateral. All the patients were prescribed
      phenoxybenzamine (dosage range, 20-120 mg/day) preoperatively. Two thirds of the
      patients had improved blood pressure 1 year after the operation. No malignancy
      was reported after a mean follow-up period of 7 years. CONCLUSION: Our series of
      patients with phaeochromocytomas commonly had a high frequency of normotension
      and extra-adrenal tumours. A high index of clinical suspicion and appropriate
      biochemical investigations are necessary to make the diagnosis, especially for
      patients manifesting adrenal incidentaloma and extra-adrenal lesion.

PMID- 20683067
TI  - Early adolescent outcome of attention-deficit hyperactivity disorder in a Chinese
      population: 5-year follow-up study.
AB  - OBJECTIVE: To examine early adolescent outcome of attention-deficit hyperactivity
      disorder in local Chinese children. DESIGN: Cohort study. SETTING: A university
      teaching hospital in Hong Kong. PARTICIPANTS: A cohort of Chinese children with
      attention-deficit hyperactivity disorder diagnosed according to the Diagnostic
      and Statistical Manual of Mental Disorders (4th edition) who attended a day
      hospital between January 1998 and December 2003. MAIN OUTCOME MEASURES: Data on
      psychopathology, academic attainment, delinquency, substance use, and other
      psychosocial functioning collected from multiple informants and official records.
      Performances of subjects were compared with a group of community controls.
      RESULTS: A total of 150 children with attention-deficit hyperactivity disorder
      were reassessed 6 years after initial intake assessment (mean age, 14 years;
      follow-up rate, 86%). Compared with the controls, their externalising and
      internalising disturbances were 4 and 1.5 times more common, respectively.
      Adolescents with attention-deficit hyperactivity disorder were more likely to
      smoke cigarettes and use illicit drugs. Their academic attainment was below age
      norms with more than one fourth repeating grades; 7% of them had been arrested by
      the police compared with none of the controls. They faced more difficulties in
      the family environment and social problem-solving. There were discrepancies
      between parent and patient reports about their attention-deficit hyperactivity
      disorder symptoms, and officially recorded youth reports of delinquency.
      CONCLUSION: Local Chinese children with attention-deficit hyperactivity disorder
      are at significant risk of multiple forms of adolescent maladjustment. Their
      outcome profile is similar to that reported in the West.

PMID- 20683068
TI  - Relationship between age and peripapillary retinal nerve fibre layer thickness:
      an optical coherence tomography study.
AB  - OBJECTIVE: To evaluate the relationship between age and peripapillary retinal
      nerve fibre layer thickness in healthy Chinese subjects. DESIGN: Cross-sectional
      study. SETTING: Regional hospital, Hong Kong. PARTICIPANTS: Healthy volunteers
      (n=218) of Chinese ethnicity with spherical equivalent of -6 to +4 dioptres were
      recruited for study from October 2001 to March 2003. Ocular examination was
      carried out and measurements of peripapillary retinal nerve fibre layer thickness
      were performed using optical coherence tomography (Carl Zeiss Humphrey OCT 2
      machine), in a circular pattern of 3.4 mm diameter, centred on the optic disc.
      MAIN OUTCOME MEASURES: Mean retinal nerve fibre layer thickness and age. RESULTS:
      The mean age was 40 (standard deviation, 17; range, 11-69) years. The mean
      peripapillary retinal nerve fibre layer thickness was 111.6 (standard deviation,
      18.5; range, 52.0-155.0) micrometres. Age correlated significantly with
      peripapillary retinal nerve fibre layer thickness (r= -0.28, P<0.0001).
      CONCLUSION: Mean peripapillary retinal nerve fibre layer thickness (based on
      optical coherence tomography) correlates negatively with age, which can interfere
      with the assessment and monitoring of glaucoma patients. An age-adjusted
      normogram may be necessary to interpret results.

PMID- 20683069
TI  - Antibiotic lock solutions for the prevention of catheter-related bacteraemia in
      haemodialysis patients.
AB  - OBJECTIVE: To investigate the effect of antibiotic lock solutions for preventing
      catheter-related bacteraemia in patients receiving haemodialysis. DESIGN:
      Retrospective study. SETTING: University teaching hospital, Hong Kong. PATIENTS:
      Consecutive patients from March 2006 to April 2007 who had central venous
      catheter insertion for haemodialysis in our centre were included in this
      historically controlled study. In all, 75 patients had catheters with heparin
      solution alone and 74 had catheters with a gentamicin antibiotic lock. The
      majority of catheters were non-tunnelled (95%). Cumulative catheter survival free
      of catheter-related bacteraemia in the two groups was compared. RESULTS: Baseline
      characteristics in the two groups were similar apart from a slightly lower serum
      albumin level in those with gentamicin locks. There were 18 and five catheter
      related bacteraemia episodes before and after recourse to gentamicin antibiotic
      locks, respectively. Staphylococcus aureus contributed to over half (65%) of the
      total bacteraemia episodes. Use of gentamicin antibiotic locks significantly
      reduced catheter-related bacteraemia episodes per 1000 catheter days from 4.6 to
      1.5 (P=0.002). Kaplan-Meier survival analysis using the log rank test showed
      significantly better bloodstream infection-free survival associated with using
      gentamicin antibiotic locks (P=0.032). A similar survival advantage was
      associated with gentamicin antibiotic locks when the analysis was restricted to
      non-tunnelled catheters. There was no significant association of catheter-related
      bacteraemia with patient age, obesity, gender, baseline serum albumin level, or
      diabetes mellitus. No serious adverse events were attributable to the use of
      gentamicin antibiotic locks. CONCLUSION: Use of gentamicin lock solutions
      effectively reduced catheter-related bacteraemia in haemodialysis patients,
      including those with non-tunnelled catheters.

PMID- 20683070
TI  - Fetoscopic laser photocoagulation in the management of twin-twin transfusion
      syndrome: local experience from Hong Kong.
AB  - OBJECTIVE: To review the perinatal outcome of monochorionic twin pregnancies
      treated by fetoscopic laser coagulation for twin-twin transfusion syndrome.
      DESIGN: Retrospective study. SETTING: A university teaching hospital in Hong
      Kong. PATIENTS: Thirty consecutive cases of fetoscopic laser coagulation of
      placental anastomoses for twin-twin transfusion syndrome performed in a single
      centre. MAIN OUTCOME MEASURES: Operative complications and perinatal survival
      rates. RESULTS: The median gestational age at initial presentation, laser
      photocoagulation, and delivery were 22 (range, 16-27) weeks, 23 (18-28) weeks,
      and 32 (21-37) weeks, respectively. To improve the visualisation, in three cases
      amnio-exchange was undertaken; the procedure was abandoned in two due to poor
      visualisation. The overall fetal survival rate, the double infant survival rate,
      and survival rate for at least one twin were 72% (43/60), 60% (18/30), and 83%
      (25/30), respectively. The most common peri-operative complication was bleeding
      from the uterine wall into the amniotic cavity, which affected three (10%)
      patients. CONCLUSIONS: Our results of fetoscopic laser surgery for twin-twin
      transfusion syndrome were similar to those in specialised centres in other
      countries.

PMID- 20683071
TI  - Should lidocaine spray be used to ease nasogastric tube insertion? A double
      blind, randomised controlled trial.
AB  - OBJECTIVE: To investigate the efficacy and safety of lidocaine nasal spray before
      nasogastric tube insertion in an emergency department. DESIGN: Double-blind,
      randomised controlled study. SETTING: Emergency department of a major regional
      hospital in Hong Kong. PATIENTS: A total of 206 adult patients, for whom
      nasogastric tube insertion was indicated. MAIN OUTCOME MEASURES: Primary outcome
      was discomfort gauged on a visual analogue scale, and Likert scale addressing
      difficulty of nasogastric tube insertion. RESULTS: Compared with placebo spray
      use, lidocaine spray use was associated with less patient discomfort, and less
      difficulty in nasogastric tube insertion, both difference being statistically
      significant. CONCLUSION: Intranasal lidocaine spray before nasogastric tube
      insertion was safe and effective in reducing patient discomfort related to the
      procedure.

PMID- 20683072
TI  - Surgical excision for challenging upper limb nerve sheath tumours: a single
      centre retrospective review of treatment results.
AB  - OBJECTIVE: To review the accuracy of different investigation modalities for upper
      limb nerve sheath tumours and the resulting surgical outcomes, and propose a
      standard algorithm to deal with such tumours to minimise complications. DESIGN:
      Retrospective review. SETTING: Regional hospital, Hong Kong. PATIENTS: All
      patients with upper limb nerve sheath tumours being excised in our hospital from
      1999 to 2008. MAIN OUTCOME MEASURES: The accuracy rate of different
      investigations, as well as corresponding neurological deficits after excision and
      recurrence rates. RESULTS: A total of 23 (10 male and 13 female) patients, aged
      between 28 and 72 (mean, 46) years, underwent excision of 25 lesions during the
      study period. The mean duration of symptom was 2.5 years and tumour size ranged
      from 1 to 10.5 cm (mean, 2.6 cm). A majority (80%) presented with a typical
      triad; only one had a true neurological deficit. Twenty-two ultrasonography and
      20 magnetic resonance images were obtained, with a diagnostic accuracy of 77% and
      100%, respectively. Eight fine-needle aspiration cytology examinations and two
      core biopsies were performed, which had respective accuracy rates of 13% and
      100%. Fifteen patients experienced neurological deficits after the operation;
      three showed spontaneous recovery. Among 12 patients with long-term residual
      neurological sequelae, five had both motor and sensory deficits and four had
      moderate-to-severe disability. No recurrence was reported. CONCLUSION: Nerve
      sheath tumours in the hand need to be managed with care. Among the different
      investigation modalities, magnetic resonance imaging was considered to be the
      gold standard. Yet ultrasonography is still the most easily accessible and least
      invasive investigation in public hospital setting. Complications are liable to
      ensue even if patients are managed by hand specialists. Thus, well-planned
      operations and detailed discussions with the patient are important prerequisites
      before operation.

PMID- 20683073
TI  - Neuroimaging techniques in epilepsy.
AB  - OBJECTIVE: To review state-of-the-art neuroimaging modalities in epilepsy and
      their clinical applications. DATA SOURCES AND STUDY SELECTION: PubMed literature
      searches to March 2010, using the following key words: 'epilepsy', 'positron
      emission tomography (PET)', 'single photon emission computed tomography (SPECT)',
      'MR volumetry', 'diffusion tensor imaging', and 'functional MR imaging'. DATA
      EXTRACTION: All articles including neuroimaging techniques in epilepsy were
      included in the review. DATA SYNTHESIS: High-field magnetic resonance imaging is
      fundamental for high-resolution structural imaging. Functional radionuclide
      imaging (positron emission tomography/single-photon emission computed tomography)
      can provide additional information to improve overall accuracy, and show good
      results with high concordance rates in temporal lobe epilepsy. Magnetic resonance
      spectroscopy is a useful adjunct consistently demonstrating changing metabolites
      in the epileptogenic region. Magnetic resonance volumetric imaging shows
      excellent sensitivity and specificity for temporal lobe epilepsy but thus far it
      has been inconsistent for extratemporal epilepsy. Diffusion tensor imaging with
      tractography allows visualisation of specific tracts such as connections with the
      language and visual cortex to enhance preoperative evaluation. Functional
      magnetic resonance imaging using blood oxygen level-dependent activation
      techniques is mainly used in presurgical planning for the high-sensitivity
      mapping of the eloquent cortex. Both contrast-bolus and arterial spin labelling
      magnetic resonance perfusion imaging show good correlation with clinical
      lateralisation of seizure disorder. CONCLUSION: Structural imaging is essential
      in localisation and lateralisation of the seizure focus. Functional radionuclide
      imaging or advanced magnetic resonance imaging techniques can provide
      complementary information when an epileptogenic substrate is not identified or in
      the presence of non-concordant clinical and structural findings.

PMID- 20683074
TI  - Diagnostic challenges of human brucellosis in Hong Kong: a case series in two
      regional hospitals.
AB  - A retrospective analysis of six patients diagnosed with brucellosis in two
      regional hospitals was carried out. The epidemiological, clinical, and laboratory
      features were studied. All patients had exposure history. Three patients
      presented with musculoskeletal symptoms, while three had predominantly
      genitourinary symptoms. One patient did not have fever at presentation. All
      patients were diagnosed by positive blood culture of Brucella melitensis, and the
      diagnosis was not suspected for all except one patient at presentation. Given the
      inferior sensitivity of blood culture to serology, human brucellosis may be
      underdiagnosed, especially when the index of suspicion is low.

PMID- 20683075
TI  - Torsion of a nongravid myomatous uterus: radiological features and literature
      review.
AB  - Torsion of the nongravid uterus is a rare but potentially fatal acute abdominal
      condition. The non-specific clinical presentation of this condition makes
      preoperative diagnosis difficult. We describe a patient with uterine torsion in
      whom the diagnosis was made using contrast-enhanced computed tomography with
      multiplanar reconstruction. Features of uterine torsion and its complications can
      be demonstrated by computed tomography, which is an important means of making a
      preoperative diagnosis.

PMID- 20683076
TI  - Reversal of pale-to-dark nasopharyngeal follicle ratio on narrow-band imaging.
AB  - Normal nasopharyngeal mucosa contains varying amounts of lymphoid tissue, which
      in adults may be minimal or absent. Nasopharyngeal mucosa with minimal lymphoid
      tissue has a regular follicular pattern on narrow-band imaging; pale follicles
      have thin, dark borders and the ratio of the pale follicle to the dark border
      (pale-to-dark ratio) is roughly 90%. In some patients undergoing routine
      nasopharyngeal endoscopy, the pale-to-dark ratio is reversed on narrow-band
      imaging, with dark centres surrounded by pale borders and a pale-to-dark ratio of
      roughly 50%. These dark follicles may represent abnormal capillary loops, as they
      have the same appearance as microvascular changes seen on narrow-band imaging of
      the oesophageal mucosa which indicate dysplasia or malignancy. While this
      observed change in the follicular pattern may be an early event in the evolution
      of nasopharyngeal carcinoma, the significance of this finding remains to be
      confirmed by a larger-scale study.

PMID- 20683077
TI  - Clostridium perfringens liver abscess with massive haemolysis.
AB  - Liver abscesses are commonly caused by Enterobacteriaceae and anaerobes. This
      report is of a patient with liver abscess with massive haemolysis and multiorgan
      failure caused by Clostridium perfringens. Despite the reportedly high mortality
      rate and poor prognostic factors, the patient eventually recovered with prompt
      treatment.

PMID- 20683078
TI  - Anti-N-methyl-D-aspartate receptor encephalitis in a young woman with an ovarian
      tumour.
AB  - Anti-N-methyl-D-aspartate receptor encephalitis is characterised by psychiatric
      and neurological abnormalities and occurs in frequent association with ovarian
      teratoma. We report the first confirmed case of teratoma-associated anti-N-methyl
      D-aspartate receptor encephalitis in Hong Kong in a young woman presenting with
      confusion and prominent dyskinesia, followed by a review of the current
      literature.

PMID- 20683079
TI  - Lump in perineum.

PMID- 20683080
TI  - Sonographic diagnosis of emphysematous pyelonephritis in a clinically stable
      patient.

PMID- 20683081
TI  - Antibiotic prophylaxis after total joint replacement.

PMID- 20683082
TI  - The Toronto Charter for Physical Activity: a global call for action.

PMID- 20683083
TI  - Associations between intrapersonal and neighborhood environmental characteristics
      and cycling for transport and recreation in adults: baseline results from the
      RESIDE study.
AB  - BACKGROUND: This study investigated the relationship between individual and
      neighborhood environmental factors and cycling for transport and for recreation
      among adults living in Perth, Western Australia. METHODS: Baseline cross
      sectional data from 1813 participants (40.5% male; age range 18 to 78 years) in
      the RESIDential Environment (RESIDE) project were analyzed. The questionnaire
      included information on cycling behavior and on cycling-specific individual,
      social environmental, and neighborhood environmental attributes. Cycling for
      transport and recreation were dichotomized as whether or not individuals cycled
      in a usual week. RESULTS: Among the individual factors, positive attitudes toward
      cycling and perceived behavioral control increased the odds of cycling for
      transport and for recreation. Among the neighborhood environmental attributes,
      leafy and attractive neighborhoods, access to bicycle/walking paths, the presence
      of traffic slowing devices and having many 4-way street intersections were
      positively associated with cycling for transport. Many alternative routes in the
      local area increased the odds of cycling for recreation. CONCLUSIONS: Effective
      strategies for increasing cycling (particularly cycling for transport) may
      include incorporating supportive environments such as creating leafy and
      attractive neighborhood surroundings, low traffic speed, and increased street
      connectivity, in addition to campaigns aimed at strengthening positive attitudes
      and confidence to cycle.

PMID- 20683084
TI  - Effects of perceived and objective neighborhood crime on walking frequency among
      midlife African American women in a home-based walking intervention.
AB  - BACKGROUND: Crime may be a significant barrier to physical activity for urban
      African American women, yet few studies have examined this relationship in
      intervention studies. This study examines relationships among neighborhood crime
      incidents, perceptions of crime and safety, and adherence in a walking
      intervention among urban, midlife African-American women. METHODS: The sample
      includes 148 women living in the City of Chicago. Violent crimes, disorder
      crimes, gun violence, and crime-related safety were examined. Adherence to
      walking frequency was measured as the percentage of recommended walks completed.
      RESULTS: Controlling for demographic characteristics and treatment group,
      multivariate regression analyses showed walking adherence was not associated with
      any of the crime measures or crime-related safety (R(2) = 0.130 to 0.147). The
      effect of enhanced treatment did not differ by levels of objective or perceived
      neighborhood crime or safety. Weak to moderate bivariate correlations were
      observed between objective crime measures and perceived disorder crime and crime
      related safety (r = 0.04 to 0.25). CONCLUSIONS: Weak correlations between
      perceived and objective crime measures suggest they are measuring different
      aspects of the crime environment. Future studies should examine perceived and
      objective measures in other populations and settings and other neighborhood
      social factors which may moderate crime and safety effects on outcomes of
      physical activity interventions.

PMID- 20683085
TI  - Associations between neighborhood safety, availability of recreational
      facilities, and adolescent physical activity among Canadian youth.
AB  - BACKGROUND: The safety of neighborhoods and availability of parks and facilities
      may influence adolescent physical activity independently or interactively.
      METHODS: 9114 Canadians in grades 6 to 10 completed the 2006 Health Behavior in
      School-Aged Children Survey. The outcome of interest was students' self-reported
      participation in moderate-to-vigorous physical activity outside of school. A
      composite scale based on questions measuring student perceptions of safety was
      used to capture individual perceptions of safety. In addition, schools were
      grouped into quintiles based on the mean of the perceived safety scale, used as a
      proxy for peer perceptions. The number of parks and recreational facilities
      within 5 km of schools was abstracted from a geographical information system.
      RESULTS: Moderate gradients in physical activity were observed according to
      individual and group perceptions of safety. Boys and girls with the highest
      perceptions of safety were 1.31 (95% CI: 1.17-1.45) and 1.45 (1.26-1.65) times
      more likely to be physically active, respectively, than those with the lowest
      perceptions. Compared with those who perceived the neighborhood as least safe,
      elementary students in higher quintiles were 1.31, 1.39, 1.37, and 1.56 times
      more likely to be physically active (P(trend) = 0.012). Increased numbers of
      recreational features were not related to physical activity irrespective of
      neighborhood safety. CONCLUSIONS: Individual and group perceptions of
      neighborhood safety were modestly associated with adolescents' physical activity.

PMID- 20683086
TI  - Perceived barriers to leisure-time physical activity in adults: an ecological
      perspective.
AB  - BACKGROUND: Perceived barriers are modifiable correlates of participation in
      physical activity. Associations of specific perceived barriers with participation
      in and level of walking for recreation, and other leisure-time physical activity
      (LTPA) were examined. Personal, social, and environmental factors associated with
      these perceived barriers were then examined. METHODS: From 2003 to 2004, 2
      surveys collected data on recreational walking and other LTPA, perceived barriers
      to participation, and personal, social, and environmental attributes, from 2194
      Australian adults. Zero-inflated negative binomial regression models examined
      associations of perceived barriers with walking and other LTPA. Generalized
      linear models identified the correlates of these perceived barriers. RESULTS: The
      perceived barriers of lack of motivation and time were associated with level of
      LTPA, while lack of motivation, poor health, and lack of facilities were
      associated with the odds of nonparticipation in LTPA. Personal, social, and
      environmental factors independently contributed to variations in perceived
      barriers. CONCLUSIONS: Level and likelihood of participation in LTPA are
      associated with different perceived barriers. Perceived barriers are a function
      of both nonmodifiable personal factors and potentially modifiable personal,
      social, and environmental factors. These findings suggest that the provision of
      relevant environmental opportunities and social support may effectively reduce
      perceived barriers to LTPA.

PMID- 20683087
TI  - Leisure-time physical activity: association with activity levels in other
      domains.
AB  - OBJECTIVES: To explore whether participation in leisure-time physical activity
      (LTPA) is associated with participation in occupational, housework, and transport
      related physical activity. METHODS: Population-based cross-sectional study
      covering a multistage sample of 972 subjects age 20 to 69 years. Physical
      activity was measured using the long version of the International Physical
      Activity Questionnaire. A LTPA score was calculated as follows: min/wk of walking
      + min/wk of moderate-intensity physical activity + (min/wk of vigorous-intensity
      physical activity x 2). Similar scores were generated for each domain. For
      categorical analyses, the scores were divided into 3 categories: 0 min/wk, 10-149
      min/wk, and > or = 150 min/wk. RESULTS: The proportion of subjects practicing
      less than 150 min/wk of physical activity in each domain was: leisure-time
      (69.8%), occupational (58.3%), housework (35.0%), transportation (51.9%).
      Subjects with a transport-related physical activity score equal to or above 150
      min/wk were 40% less likely to be sedentary in leisure-time in comparison with
      those who did not practice transport-related physical activity. Housework and
      occupational physical activity were not related to participation in LTPA.
      CONCLUSIONS: Future physical activity campaigns should focus on other domains
      instead of LTPA alone, particularly supporting transport-related physical
      activity as a strategy of health promotion.

PMID- 20683088
TI  - Co-varying patterns of physical activity and sedentary behaviors and their long
      term maintenance among adolescents.
AB  - BACKGROUND: We examined the covarying patterns of physical activity and sedentary
      behaviors among adolescents and their long-term maintenance. METHODS: Data came
      from the National Longitudinal Study of Adolescent Health (1995-2002). We used
      latent class analysis to identify distinct covarying patterns in adolescence.
      Logistic regression models were used to predict odds of meeting moderate-to
      vigorous physical activity (MVPA) recommendations (> or = 5 bouts/week) and
      exceeding screen time guidelines (> 2 hours/day) 6 years later based on their
      adolescent class profile. RESULTS: Five classes for each gender were identified
      and labeled as low physical activity (PA)/low sedentary behaviors (SED), moderate
      (Mod) PA/high (HI) SED, Mod PA/low SED, HI PA/low SED, and HI PA (except
      skating/biking)/low SED. Compared with low PA/low SED, males and females in Mod
      PA/low SED, HI PA/low SED, and HI PA (except skating/biking)/low SED classes had
      increased odds of meeting MVPA recommendations in young adulthood. Mod PA/HI SED
      had higher odds of exceeding screen time guidelines in young adulthood (adjusted
      odds ratio [AOR] for females: 1.67, 95% CI: 1.00-2.81; AOR for males: 3.31, 95%
      CI: 1.80-6.09). CONCLUSIONS: Findings are useful to aid the development of
      multifactorial interventions that promote physical activity and reduce screen
      time among adolescents transitioning to adulthood.

PMID- 20683089
TI  - Effect of elimination games on physical activity and psychosocial responses in
      children.
AB  - BACKGROUND: This study evaluated the effect of elimination and nonelimination
      games on objectively measured physical activity and psychosocial responses in
      children. METHODS: A total of 29 children in grades 4 to 6 (65.5% male; 10.5 +/-
      1.0 years old) wore an accelerometer while participating in 2 elimination and 2
      nonelimination games. Activity counts were collected using a 30-second epoch and
      converted to METs to determine minutes spent in sedentary behavior and light,
      moderate, vigorous, and moderate-to-vigorous physical activity. Self-efficacy,
      enjoyment, and peer-victimization were assessed on 4 occasions (before and after
      2 elimination and 2 nonelimination games). RESULTS: Overall, girls spent more
      time in sedentary behavior compared with boys. Children engaged in significantly
      more moderate-to-vigorous physical activity during nonelimination games compared
      with elimination games. Furthermore, children significantly increased self
      efficacy after playing both game sessions. A significant interaction between type
      of game and time of measurement in the prediction of enjoyment showed that
      enjoyment modestly increased after elimination games and slightly decreased after
      nonelimination games. There were no differences in peer-victimization.
      CONCLUSION: This study provides preliminary evidence that nonelimination games
      provide more moderate-to-vigorous physical activity compared with elimination
      games, but elimination games may be more enjoyable.

PMID- 20683090
TI  - Direct observation of children's preferences and activity levels during
      interactive and online electronic games.
AB  - BACKGROUND: Interactive electronic games have recently been popularized and are
      believed to help promote children's physical activity (PA). The purpose of the
      study was to examine preferences and PA levels during interactive and online
      electronic games among overweight and nonoverweight boys and girls. METHODS:
      Using a modification of the SOFIT, we systematically observed 70 Hong Kong
      Chinese children (35 boys, 35 girls; 50 nonoverweight, 20 overweight), age 9 to
      12 years, during 2 60-minute recreation sessions and recorded their game mode
      choices and PA levels. During Session One children could play either an
      interactive or an online electronic bowling game and during Session Two they
      could play an interactive or an online electronic running game. RESULTS: Children
      chose to play the games during 94% of session time and split this time between
      interactive (52%) and online (48%) versions. They engaged in significantly more
      moderate-to-vigorous physical activity (MVPA) during interactive games than their
      online electronic versions (70% vs. 2% of game time). Boys and nonoverweight
      children expended relatively more energy during the interactive games than girls
      and overweight children, respectively. CONCLUSIONS: New-generation interactive
      games can facilitate physical activity in children, and given the opportunity
      children may select them over sedentary versions.

PMID- 20683091
TI  - Permanent play facilities in school playgrounds as a determinant of children's
      activity.
AB  - BACKGROUND: To investigate whether the number of permanent playground facilities
      in schools influences objectively measured physical activity. METHODS: Physical
      activity was measured using Actical accelerometers over 2 to 5 days in 417
      children (5-12 years) from 7 schools. The number of permanent play facilities
      likely to encourage physical activity in individuals or groups of children (eg,
      adventure playgrounds, swings, trees, playground markings, courts, sandpits) were
      counted on 2 occasions in each school. The surface area of each playground (m(2))
      was also measured. RESULTS: The number of permanent play facilities in schools
      ranged from 14 to 35 and was positively associated with all measures of activity.
      For each additional play facility, average accelerometry counts were 3.8% (P <
      .001) higher at school and 2.7% (P < .001) higher overall. Each additional play
      facility was also associated with 2.3% (P = .001) or 4 minutes more
      moderate/vigorous activity during school hours and 3.4% (P < .001) more (9
      minutes) over the course of the day. School playground area did not affect
      activity independent of the number of permanent play facilities. Findings were
      consistent across age and sex groups. CONCLUSION: Increasing the number of
      permanent play facilities at schools may offer a cost-effective and sustainable
      option for increasing physical activity in young children.

PMID- 20683092
TI  - Adolescent physical activity: does implementation intention have a role?
AB  - BACKGROUND: The current study tested the utility of an integrated social
      cognitive model to predict physical activity (PA) intentions and behavior in New
      Zealand adolescents. METHOD: Seventy-two adolescents (mean age = 16.92, SD =
      0.66) completed measures consistent with the integrated model (attitude,
      subjective norm, perceived behavioral control [PBC], goal intention, task
      efficacy, barrier efficacy, and implementation intention). Pedometer data (Yamax
      SW200 pedometer) were collected for 7 days, and a self-report 7-day recall
      questionnaire was administered at the end of this week. A series of hierarchical
      regression analyses were conducted to examine the contribution of the model to PA
      goal intention, implementation intention, self-reported and objective PA.
      RESULTS: The integrated model accounted for 41% of goal intention, 33% of
      implementation intention, and 41% and 18% of subjectively and objectively
      measured PA, respectively. PBC had the strongest association with goal intention
      whereas attitude had the strongest association with implementation intention.
      Task-efficacy made the greatest contribution to objectively measured PA, whereas
      implementation intention had the strongest association with subjectively measured
      PA. CONCLUSION: These findings have implications regarding PA measurement in
      adolescent populations, and suggest that social cognitive variables play an
      important role in adolescent PA. Recommendations for future research are
      discussed.

PMID- 20683093
TI  - Errors in MET estimates of physical activities using 3.5 ml x kg(-1) x min(-1) as
      the baseline oxygen consumption.
AB  - PURPOSE: To compare intensity misclassification and activity MET values using
      measured RMR (measMET) compared with 3.5 ml x kg(-1) x min(-1) (standMET) and
      corrected METs [corrMET = mean standMET x (3.5 / Harris-Benedict RMR)] in
      subgroups. METHODS: RMR was measured for 252 subjects following a 4-hr fast and
      before completion of 11 activities. VO2 was measured during activity using
      indirect calorimetry (n = 2555 activities). Subjects were classified by BMI
      category (normal-weight or overweight/obese), sex, age (decade 20, 30, 40, or 50
      y), and fitness quintiles (low to high). Activities were classified into low,
      moderate, and vigorous intensity categories. RESULTS: The (mean +/- SD) measMET
      was 6.1 +/- 2.64 METs. StandMET [mean (95% CI)] was (0.51(0.42, 0.59) METs) less
      than measMET. CorrMET was not statistically different from measMET (-0.02 (-0.11,
      0.06) METs). 12.2% of the activities were misclassified using standMETs compared
      with an 8.6% misclassification rate for METs based on predicted RMR (P < .0001).
      StandMET differences and misclassification rates were highest for low fit,
      overweight, and older individuals while there were no differences when corrMETs
      were used. CONCLUSION: Using 3.5 ml x kg(-1) x min(-1) to calculate activity METs
      causes higher misclassification of activities and inaccurate point estimates of
      METs than a corrected baseline which considers individual height, weight, and
      age. These errors disproportionally impact subgroups of the population with the
      lowest activity levels.

PMID- 20683094
TI  - Results of a randomized trial testing messages tailored to participant-selected
      topics among female college students: physical activity outcomes.
AB  - BACKGROUND: A better understanding of identifying tailoring variables would
      improve message design. Tailoring to a behavior that a participant selects as one
      they would like to work on may increase message relevance, and thus
      effectiveness. This trial compared 3 groups: message tailored to physical
      activity as a participant-selected topic (choice), message tailored to physical
      activity as an expert-determined topic (expert), or nontailored message
      (comparison). METHODS: 408 female college students received web-delivered
      computer-tailored messages on physical activity. Outcomes were immediate and 1
      month follow-up changes in psychosocial, goal-related, and behavioral variables
      related to physical activity. RESULTS: Participants were predominately non
      Hispanic White (73.8%). Change in self-efficacy and goal commitment at immediate
      follow-up and vigorous physical activity at 1-month follow-up was greater in the
      expert versus comparison group. Change in goal commitment at immediate follow-up
      was lower in the choice versus expert group. In the expert group, those choosing
      physical activity as their selected topic perceived the goal to be easier at
      immediate follow-up compared with those receiving unmatched messages.
      CONCLUSIONS: Findings supported tailoring to an expert-determined topic. However,
      based on the beneficial change in perceived goal difficulty when topics matched,
      future research should encourage synchrony between participant-selected topics
      and expert recommendations.

PMID- 20683095
TI  - Internet reporting of weekly physical activity behaviors: the WIN Study.
AB  - BACKGROUND: Self-report measures have been validated and are widely used.
      Interest currently lies in the development of simple, valid methods that can be
      used in any location to determine level of PA in large populations/samples. The
      purpose of this report is to illustrate tracking of physical activity behaviors
      and musculoskeletal injury reports on a weekly basis via the Internet. METHODS:
      The Women's Injury Study (WIN) methodology includes use of BRFSS-related physical
      activity items that are completed online by more than 900 women weekly for an
      average of 3 years. RESULTS: With more than 45,000 weekly physical activity and
      injury logs, the percentage of total logs submitted via online records is 91%.
      Self-reported pedometer steps are consistent with similar, smaller research
      samples. CONCLUSIONS: This report suggests that Internet tracking is a viable
      means of assessing nearly real-time physical activity, describes the process of
      developing and monitoring self-reported physical activity behaviors via the
      Internet, and provides recommendations for others considering such methods.

PMID- 20683096
TI  - Evaluating a brief self-report measure of neighborhood environments for physical
      activity research and surveillance: Physical Activity Neighborhood Environment
      Scale (PANES).
AB  - BACKGROUND: Neighborhood environment attributes of walkability and access to
      recreation facilities have been related to physical activity and weight status,
      but most self-report environment measures are lengthy. The 17-item PANES
      (Physical Activity Neighborhood Environment Scale) was developed to be
      comprehensive but brief enough for use in multipurpose surveys. The current study
      evaluated test-retest and alternate-form reliability of PANES items compared with
      multi-item subscales from the longer NEWS-A (Neighborhood Environment Walkability
      Scale--Abbreviated). METHODS: Participants were 291 adults recruited from
      neighborhoods that varied in walkability in 3 US cities. Surveys were completed
      twice with a 27-day interval. RESULTS: Test-retest ICCs for PANES items ranged
      from .52 to .88. Spearman correlations for the PANES single item vs NEWS-A
      subscale comparisons ranged from .27 to .81 (all P < .01). CONCLUSIONS: PANES
      items related to land use mix, residential density, pedestrian infrastructure,
      aesthetic qualities, and safety from traffic and crime were supported by
      correlations with NEWS-A subscales. Access to recreation facilities and street
      connectivity items were not supported. The brevity of PANES allows items to be
      included in studies or surveillance systems to expand knowledge about
      neighborhood environments.

PMID- 20683097
TI  - Comparison of a subjective and an objective measure of physical activity in a
      population sample.
AB  - BACKGROUND: The aim of this study was to compare physical activity components in
      the long, self-administrated version of IPAQ with an accelerometer in a
      population sample. METHODS: In total 980 subjects (18-65 years) wore an
      accelerometer (Actigraph) for 7 consecutive days and thereafter filled in the
      IPAQ. Measures of total physical activity, time spent in moderate and in vigorous
      activity as well as time spent sitting as assessed by the IPAQ and the Actigraph
      were compared. RESULTS: The results showed significant low to moderate
      correlations (Rs = 0.07-0.36) between the 2 instruments and significantly (P <
      .001) higher values for sitting and vigorous intensity physical activity from the
      IPAQ compared with the Actigraph. The higher the values reported by the IPAQ the
      bigger differences were seen between the instruments. Comparison between the
      tertiles of total physical activity by the 2 instruments showed significant
      overall association with consistent agreement in the low and the high tertiles.
      CONCLUSION: The long form of IPAQ is a valid measure of physical activity in
      population research. However, the IPAQ likely overestimates actual physical
      activity as shown by its limited ability to classify adults into low and high
      categories of physical activity based on accelerometer data.

PMID- 20683098
TI  - Attitudes and the environment as determinants of active travel in adults: what do
      and don't we know?
AB  - BACKGROUND: Walking and cycling for transport, or 'active travel,' has the
      potential to contribute to overall physical activity levels. However, a wide
      range of factors are hypothesized to be associated with adult's active travel
      behavior. This paper describes current knowledge of the psychological and
      environmental determinants of active travel in adults, and considers ways in
      which the 2 domains can be better integrated. METHODS: Quantitative studies were
      reviewed which examined psychological and environmental influences on active
      travel in an adult population. Studies were classified according to whether they
      examined psychological, environmental or both types of factor. RESULTS: Fourteen
      studies were identified which examined psychological correlates of active travel
      behavior in adults, and 36 which examined environmental correlates. Seven studies
      were identified which considered both domains, of which only 2 of explored the
      interactions between personal, social and environmental factors. The majority of
      the evidence is helpful in identifying correlates rather than determinants of
      active travel behavior. CONCLUSIONS: To further our understanding of the
      influences of active travel, there is a need for more research which integrates
      both individual and environmental domains and examines how they interact.

PMID- 20683099
TI  - Evaluation of the effect of IL-22 on human cord blood CD4+ T cells.
AB  - IL-22 is a member of IL-10 cytokine family which is believed to play an important
      role in inflammatory responses. IL-22 has similarities with IL-10 including
      conserved sequences with IL-10. IL-22 receptor is also comprised of two chains
      known as L-22R1 and L-10R2; supporting the speculation that the two cytokines may
      have similar effects. The aim of this study was to shed some light on the
      biological activity of IL-22 upon the cord blood CD4+CD25- T cells. In this
      research, cord blood T CD4+CD25- cells were cultured in presence of anti
      CD2/CD3/CD28 coated beads, IL-2 and IL-22 for two weeks at 37 degrees C and 5%
      CO2. Flow cytometry analysis showed that IL-22 has no effect upon CD25 and Foxp3
      expression. Also, the results indicated that IL-22 is not involved in CD4+ T cell
      proliferation. Moreover, the results of suppression assay did not show any
      suppression effect on the cultured T cells. Thus, it seems that umbilical cord
      blood T cells probably do not express IL-22R1 on their surface.

PMID- 20683100
TI  - Cytotoxicity of human cord blood natural killer cells is enhanced by recombinant
      interleukin-15.
AB  - Hematopoietic cord blood (CB) stem cell transplantation has more advantages to
      other cell sources because of lower Graft Versus Host Disease (GVHD). Interleukin
      15(IL-15) is an immunoregulatory cytokine, known to enhance cytolytic function of
      cord Natural Killer (NK) cells. The aim of this study was to investigate the
      effect of IL-15 on NK cytotoxicity simultaneously in different cell death stages.
      We compared the ability of IL-15 to enhance the NK cytotoxicity of CB in
      comparison to adult blood Mononuclear Cells (MNCs) against K562 target cells by
      co-staining with AnnexinV-FITC and Propidium Iodide after 3.5 h incubation at 37 
      degrees C and 5% CO2 by using flow cytometric method. We also evaluated
      phenotypic changes after treatment by IL-15 in both cell sources. Our results
      indicated that CB samples had lower level of apoptosis, while necrosis was
      negligible; also by escalating Effector: Target (E: T), we got higher level of
      apoptosis and necrosis in peripheral blood (PB). NK activity of cord and adult
      MNCs was enhanced by incubation with IL-15 (10 ng/ml) for 72 h with significantly
      higher results of PB in comparison to CB (p<0.0001). Moreover, IL-15 increased
      the percentage of CD3-/CD56+ and CD25+ cells after 72 h incubation. Results
      showed incubation with human recombinant (hr) IL-15 for 3 days increased NK
      activity. Taken together, these results indicated that NK cytotoxicity of CB MNCs
      could be augmented by human recombinant (hr) IL-15, but this activity did not
      reach to same level of PB counterparts. We established that CD25 expression on CB
      MNCs could be increased with IL-15, in 72-hour cultures, but to a lesser degree
      compared to that on corresponding adult PB MNCs.

PMID- 20683101
TI  - Effect of TGFbeta1 and TIMP2 on disease activity in asthma and COPD.
AB  - The process of bronchial tissue repair/remodeling depends on balance between
      production and degradation achieves the regulation of extracellular matrix
      turnover. We designed this study to evaluate relation between Transforming Growth
      Factor Beta1 (TGFbeta1) and Tissue Inhibitory of Metaloproteinase 2 (TIMP2) as
      two main tissue mediators on activity and reversibility of asthma and chronic
      obstructive pulmonary disease (COPD). In a cross sectional study we evaluated
      TIMP2 and TGFbeta1 expression in two groups of 29 asthmatic (14 males and 15
      females) and 13 male COPD patients using semi-quantitative PCR on induced sputum
      samples. The relation between TIMP2 and TGFbeta1 and PFT indices and disease free
      period were assessed. The COPD patients with raised expression of both TGFbeta1
      and TIMP2 had better pulmonary function test (PFT) indices and also longer
      disease free period. In contrast patients with chronic asthma could remain in
      well pulmonary function status with raised TIMP2 and decreased TGFbeta1
      expression. We supposed that underlying inflammatory process is the main reason
      for the different effect of cytokines in asthma and COPD. It raises concern about
      critical role of corticosteroids consumption on various cytokines expression.
      Furthermore TGFBeta1 may be served as a biomarker in sputum for assessing disease
      activity and evidence based prescribing corticosteroids in patients with COPD and
      asthma.

PMID- 20683102
TI  - Immunochemical characterization of Amaranthus retroflexus pollen extract:
      extensive cross-reactive allergenic components among the four species of
      Amaranthaceae/Chenopodiaceae.
AB  - The importance of Amaranthus retroflexus pollen in causing respiratory allergy
      has been well ascertained in many countries including Iran with a high positive
      rate (69%) among Iranian allergic patients. The aim of the present study is to
      identify the allergenic properties of A. retroflexus pollen. Sixteen patients
      with allergy to A. retroflexus pollen were selected for the study. The antigenic
      and allergenic profiles of the A. retroflexus pollen extract as well as pollen
      extracts from other species of the Amaranthaceae/Chenopodiaceae family, including
      Chenopodium album, Kochia scoparia, and Salsola kali, were evaluated by ELISA,
      immunoblotting, and immunoblot inhibition assays. The resolved protein fractions
      on SDS-PAGE ranged from 10-85 kDa. Several allergenic components (MW 85, 45, 39,
      18, 15, and 10 kDa) of the A. retroflexus pollen extract were recognized by using
      patients' sera by specific antibody of IgE class using ELISA and immunoblot
      assays. The IgE reactivity of the A. retroflexus pollen extract was partially
      inhibited by all three pollen extracts tested. The inhibition by the S. kali
      pollen extract was more than those by other pollen extracts. Moreover, the wheal
      diameters by the A. retroflexus pollen extract were highly correlated with those
      by C. album, K. scoparia and S. kali pollen extracts. In conclusion, three
      proteins with apparent MWs of 39, 45, and 66 kDa are suggested as the common
      allergenic components among the four pollens from the
      Amaranthaceae/Chenopodiaceae family. It appears that there are some common
      (similar) epitopes among the four common allergenic pollens.

PMID- 20683103
TI  - Characterization and stability of specific IgE to white egg's, gliadin's and
      peanut's proteins among children.
AB  - The aim of the present study was to characterize allergen-specific immunoglobulin
      E (IgE) among children in Fez region. Eighty one children were recruited from the
      Hospital University Center of Fez. All of them had completed a questionnaire
      before taking sera. The sera were used to measure total IgE and specific data to
      proteins of egg's white (EWP), peanuts (PP) and gliadins (G). In last part, we
      studied the reactivity of specific IgE to native and to heat- and acid-treated
      allergens. Allergen-specific IgE measurement indicated more positive values for
      gliadins (46.9% up to 2IU/ml) than egg white's (29.6%) and peanut's proteins
      (22.2%). According to predictive values published by Sampson (2001), 14.3% of
      children are sensitive to egg white's proteins, 4.1% to gliadins and 2.7% to
      peanut's proteins. The allergenic potential of EWP and gliadins among children
      were partially diminished by heat and acid treatment. Allergen-specific IgE
      measurement indicates that children from Fez region are more sensitive to EWP
      than peanut's proteins and gliadins. Treatments of these food proteins indicated
      that recognition by children IgE can be reduced by thermal or acid treatment of
      these allergens.

PMID- 20683104
TI  - Effects of N-acetylcysteine on asthma exacerbation.
AB  - Airway mucus hypersecretion and increased oxidative stress are clinical and
      pathophysiological features of asthma exacerbation. We studied effects of N
      acetylcysteine (NAC) as a mucolytic and antioxidant agent in asthma exacerbation.
      In this randomized, single-blinded, placebo-controlled study 50 patients ( 17
      male, 33 female, mean age 48.94+/-13.68) with asthma exacerbation were randomized
      to receive either oral 600 mg b.d. N-acetylcysteine or placebo in addition to
      standard treatment during 5 days hospitalization. Daily measurements of wheezing,
      dyspnea, cough, sputum, expectoration, night sleep scores and morning PEFR were
      performed. There was no significant difference in wheezing score between patients
      assigned NAC and those assigned placebo in day 5(0.84[SD 0.94] VS 0.87[SD 0.79])
      and also in cough score (0.72[SD 0.84] VS 0.79[SD 0.97]), dyspnea score (0.84[SD
      1.06] VS 0.91[SD 1.01]), sputum score(0.79[SD 0.83] VS 0.62[SD 0.71]),
      expectoration score(0.79[SD 0.97] VS 0.83[SD 1.09]), night sleep score(1[SD 1.17]
      VS 0.67[SD 0.98] and morning PEFR (256[SD 96.36] VS 282[SD 98.86]). We concluded
      that addition of N-acetylcysteine to usual asthma medication has no significant
      effect in treatment of asthma exacerbation.

PMID- 20683105
TI  - Predictive value of ''jones morbidity index'' in northern Iranian asthmatic
      patients.
AB  - Asthma is the major chronic respiratory inflammatory disease in all ages. The
      validity and predictability of revised Jones Morbidity Index (JMI) as a simple
      and practical tool for asthma evaluation morbidity has not yet been tested in
      Iran. This study aimed to evaluate the predictability and validity of a revised
      JMI in northern Iran. As a one-year follow up study, 210 adult asthmatic patients
      were visited in an asthma clinic in the town of Babol (north of Iran) at two
      stages. At first stage, in addition to demographic information, 3 simple
      questions of revised JMI were asked and Pulmonary Expiratory Flow Rate (PEFR) for
      each patient was measured. Based on modified JMI, patients were categorized in
      three groups: Low, Medium, and High morbidity. At the second stage, after one
      year, patients were visited again and in addition to their last year medical
      records, the same questionnaires were filled. The validity of the index checked
      by PEFR values at two stages and its predictability was evaluated by morbidity
      factors during the last year. From hundred and seventy (170) patients who were
      able to fulfil the second stage of the study, 55 patients (32%) had been
      categorized as low, 88 patients (52%) as medium, and 27 patients (16%) as high
      morbidity. The percentages of patients PEFR to the estimated normal values in
      these three categories (90.8%, 74.7%, and 55.3% respectively) were significantly
      different which shows a good correlation between PEFR values and asthma morbidity
      (p<0.001). The relative risks of high morbidity group for hospitalization from
      asthma and needing oral steroids during the one year period were 4.1 (CI = 1.27
      to 13.1), 1.96 (CI = 0.97 to 3.96) respectively which are significantly higher
      than the other two categories (P<0.05). Since the modified JMI showed an
      acceptable validity and predictability in northern patients of northern Iran, we
      recommend its use as a simple pragmatic tool for evaluating asthma morbidity in
      primary care in this region of Iran.

PMID- 20683106
TI  - Air pollution effects on peak expiratory flow rate in children.
AB  - Airway mucus hypersecretion Health effects caused by air pollutants may range
      from subtle biochemical or physiological signs, such as mildly reduced lung
      function, to difficult breathing, wheezing, coughing and exacerbation of existing
      respiratory conditions such as asthma. The aim of this study was measuring the
      adverse health effects of air pollution on lung function of primary school
      students. The lung function of students was measured daily for seven weeks in two
      elementary schools in District 12 of Tehran, after obtaining permission from the
      two principals and signed parents' consent forms. Twenty four hourly air
      pollution levels were used as potential predictors of lung function. The
      principal analysis conducted was a logistic regression on a subset of the data
      using a case-crossover design. The outcomes data consisted of the results of lung
      function tests for 356 female and 206 male students over the six-week period.
      Using the difference between mean (87) and maximum (125) concentration of moving
      average of NO in this period to judge the size of the effect, such an increase in
      NO is predicted to lead to an increase in the probability of poor lung function
      (OR=20) based on population-based predicted value. This study has shown strong
      and consistent associations between children's poor lung function and outdoor air
      pollutants in District 12 of Tehran for some pollutants. The strong association
      found in this study was an increase in seven-day moving average of NO using both
      definitions.

PMID- 20683107
TI  - Another feather in the cap: launch of international edition and activation of
      online manuscript management system.

PMID- 20683108
TI  - Effect of electronic media on children.
AB  - Radio, television (TV), movies, video games, cell phones, and computer networks
      have assumed central roles in our children's daily lives. The media has
      demonstrated potentially profound effects, both positive and negative, on
      children's cognitive, social, and behavioral development. Considering the
      increasing exposure of children to newer forms of media, we decided to review the
      current literature on the effects of media on child health both in the Western
      countries and India. It is widely accepted that media has profound influence on
      child health, including violence, obesity, tobacco and alcohol use, and risky
      sexual behaviors. Simultaneously, media may have some positive effects on child
      health. We need to find ways to optimize the role of media in our society, taking
      advantage of their positive attributes and minimizing their negative ones. We
      need to understand better how to reverse the negative impact of media and make it
      more positive.

PMID- 20683109
TI  - Backpack weight and postural angles in preadolescent children.

PMID- 20683110
TI  - Vitamin D supplementation--still in its infancy.

PMID- 20683111
TI  - Rotavirus vaccine contamination with PCV1--statement of IAP Committee on
      Immunization.

PMID- 20683112
TI  - Skin care for the newborn.
AB  - Skin of the newborn differs from that of an adult in several ways. It is more
      susceptible to trauma and infection and requires special care. Certain principles
      of skin care have to be emphasized to the mother or caregiver such as gentle
      cleansing, adequate hydration and moisturization of the skin, preventing friction
      and maceration in body folds, and protection from irritants and bright sunlight.
      The initial bath in full term infants can be given once the baby's temperature
      has stabilized and the infant is hemodynamically stable. All soaps, cleansers,
      and syndets should be used infrequently during the newborn period and it is
      better if their use is limited to groins, axillae and napkin areas. The use of
      emollients on newborns should be limited in warm weather.

PMID- 20683113
TI  - Antibiotic prophylaxis following urinary tract infection in children: a
      systematic review of randomized controlled trials.

PMID- 20683114
TI  - Thalamic pain syndrome due to cytomegalovirus vasculitis in an HIV-positive
      child.
AB  - Dejerine-Roussy syndrome, also known as the thalamic pain syndrome is a condition
      in which the body becomes hypersensitive to pain as a result of damage to the
      thalamus, a part of the brain that affects sensation. Association of this
      syndrome with HIV is rare with few case reports described in adults. We report a
      10 year old male child who was HIV positive and had developed this syndrome due
      to cytomegalovirus vasculitis.

PMID- 20683115
TI  - Phenytoin induced vitamin D deficiency presenting as proximal muscle weakness.
AB  - A 6-year-old girl presented with proximal muscle weakness of lower limbs. She was
      receiving phenytoin for epilepsy for 2 years. Serum phenytoin level was within
      therapeutic range. Serum 25(OH) vitamin D was low (5 ng/mL) and serum parathyroid
      hormone level was high. After administration of oral vitamin D, muscle weakness
      improved and vitamin D level increased to 39.11 ng/mL. Proximal muscle weakness
      due to vitamin D deficiency following phenytoin intake is rare in children.

PMID- 20683116
TI  - Cholecystoappendicostomy for progressive familial intrahepatic cholestasis.
AB  - We report a rare case of progressive familial intrahepatic cholestasis type 2
      from India. The diagnosis was confirmed on the basis of gene mutation analysis.
      The child had intense pruritus refractory to conventional medical management. As
      liver biopsy did not reveal any cirrhosis, partial external biliary diversion was
      considered as an alternative to liver transplant. We performed
      cholecystoappendicostomy rather than the conventional method of using an ileal
      loop as a conduit between the gall bladder and abdominal wall. Child recovered
      completely.

PMID- 20683117
TI  - Upper limit of normal antistreptolysin-O titer in healthy school children.
AB  - We studied the level of ASO (anti streptolysin O) titer and throat culture for
      GABHS (group A beta hemolytic streptococci) in 200 normal healthy school children
      between 5 to 15 years of age. We noted the upper limit of normal titer of 242 IU
      in the healthy school children around Mysore city. Throat culture was positive
      for GABHS in 9% of healthy school children indicating the carrier state.

PMID- 20683118
TI  - Lipid profile in high risk children aged 2-10 years.
AB  - A case-control study was conducted to study the Lipid profile of high risk
      children (age 2-10 years). There was a significant elevation of total cholesterol
      (P<0.001) and LDL (P< 0.001). Early dietary and lifestyle modifications can
      prevent this cascade.

PMID- 20683119
TI  - Diagnostic value of real time PCR for neurotuberculosis.

PMID- 20683120
TI  - Pamidronate for fibrous dysplasia due to McCune Albright Syndrome.

PMID- 20683121
TI  - Cerebral aneurysmal arteriopathy in HIV infected children.

PMID- 20683122
TI  - Episodic cluster headache: a rare diagnosis in children.

PMID- 20683123
TI  - Investigation of the cytotoxicity mechanism of silver nanoparticles in vitro.
AB  - Nowadays, more and more nanotechnology products and nanomaterials are being
      applied in our lives. Silver nanoparticles (SNPs) are used in infection
      prevention and treatment due to their antimicrobial activity. However, as a kind
      of nanomaterial, the toxicology of SNPs has not been completely studied. The
      mechanism of cytotoxicity of SNPs in vitro to mouse's fibroblast cells (L929) was
      investigated in this study. As a contrast, silver microparticles (SMPs) were also
      studied. Propidium iodide (PI) single staining and Annexin-V/PI staining were
      carried out to unveil the influence of SNPs and SMPs on the cells. A transmission
      electron microscope (TEM) was used to observe SNPs' distribution in the cells.
      The results of cell cycle analysis indicated that the cells treated with SNPs
      were arrested in the G2M phase. Meanwhile, SNPs lead to apoptosis of more cells
      compared to SMPs at the same dose as a result of apoptosis analysis. Analysis of
      the cells' ultrastructure showed that SNPs could be phagocytized into the cells
      while SMPs could not. The mechanism of cytotoxicity of SNPs in vitro to L929
      cells may be that SNPs are phagocytized into the cells and they interact with
      mitochondria or other organelles, even nuclei, which results in cells' apoptosis
      or necrosis.

PMID- 20683124
TI  - Enhanced bone forming ability of SLA-treated Ti coated with a calcium phosphate
      thin film formed by e-beam evaporation.
AB  - With an electron-beam evaporation process, a calcium phosphate (Ca-P) thin film
      of approximately 500 nm thick was deposited on sand blasted with large grits and
      acid etched (SLA) Ti without changing the typical morphology of the SLA surface.
      Dissolution behavior was investigated by measuring the amount of dissolved
      phosphate ions with ion chromatography after immersing the SLA Ti sample coated
      with a Ca-P film in 1 ml de-ionized water maintained at 37 degrees C for
      different periods of soaking time, and the surface morphology was observed with
      field emission scanning electron microscopy. The amount of phosphate ions
      increased quickly right after immersion but began to decrease after 2 days of
      immersion by redeposition with Ca ions as apatite, and the amount of biomimetic
      apatite increased with the extended soaking time. The Saos-2 cell was more
      attached on the coated surface, and the in vivo evaluation was that the Ca-P
      deposited SLA implant greatly improved the new bone formation ability.

PMID- 20683125
TI  - An investigation of the aseptic loosening of an AISI 316L stainless steel hip
      prosthesis.
AB  - The total replacement of joints by the implantation of permanently indwelling
      prosthetic components has been one of the major successes of modern surgery in
      terms of relieving pain and correcting deformity. However, the aseptic loosening
      of a prosthetic-joint component is the most common reason for joint-revision
      surgery. Furthermore, it is thought that wear particles are one of the major
      contributors to the development and perpetuation of aseptic loosening. The aim of
      the present study was to identify the factors related to the aseptic loosening of
      an AISI 316L stainless steel total hip prosthesis. The stem was evaluated by x
      ray photoelectron spectroscopy, with polished and rough regions being analyzed in
      order to establish the differences in the chemical compositions of both regions.
      Specific areas were examined using scanning electron microscopy with energy
      dispersive x-ray spectroscopy and light microscopy.

PMID- 20683126
TI  - The biological activities of (1,3)-(1,6)-beta-d-glucan and porous electrospun
      PLGA membranes containing beta-glucan in human dermal fibroblasts and adipose
      tissue-derived stem cells.
AB  - In this study, we investigated the possible roles of (1,3)-(1,6)-beta-d-glucan
      (beta-glucan) and porous electrospun poly-lactide-co-glycolide (PLGA) membranes
      containing beta-glucan for skin wound healing, especially their effect on adult
      human dermal fibroblast (aHDF) and adipose tissue-derived stem cell (ADSC)
      activation, proliferation, migration, collagen gel contraction and biological
      safety tests of the prepared membrane. This study demonstrated that beta-glucan
      and porous PLGA membranes containing beta-glucan have enhanced the cellular
      responses, proliferation and migration, of aHDFs and ADSCs and the result of a
      collagen gel contraction assay also revealed that collagen gels contract strongly
      after 4 h post-gelation incubation with beta-glucan. Furthermore, we confirmed
      that porous PLGA membranes containing beta-glucan are biologically safe for wound
      healing study. These results indicate that the porous PLGA membranes containing
      beta-glucan interacted favorably with the membrane and the topical administration
      of beta-glucan was useful in promoting wound healing. Therefore, our study
      suggests that beta-glucan and porous PLGA membranes containing beta-glucan may be
      useful as a material for enhancing wound healing.

PMID- 20683127
TI  - The release properties of silver ions from Ag-nHA/TiO2/PA66 antimicrobial
      composite scaffolds.
AB  - Implant-associated bacterial infection can jeopardize the clinical success of
      implants and result in loss of supporting bone. The purpose of this study was to
      develop a novel porous scaffold with long-term antibacterial activity for bone
      repair or regeneration. Porous nano-hydroxyapatite/titania/polyamide66 scaffolds
      containing different amounts of silver ions (Ag-nHA/TiO(2)/PA66) were prepared by
      a phase inversion technique. The release of silver ions from the porous scaffolds
      in simulated body fluid (SBF) and in the F12 cell culture medium was evaluated
      via atomic absorption spectrometry. The results showed that the release of Ag(+)
      was time and concentration dependent, increasing with the immersion time and the
      silver content in the scaffolds. On the other hand, the release property of Ag(+)
      was also influenced by the immersion medium. The cumulative Ag(+) release in the
      F12 medium with time increase parabolically, different from the linear increase
      or the zero-order release kinetics in the SBF medium. Compared to the slight
      fluctuation of the Ag(+) release rate in SBF during the whole immersion period,
      the initial fast release rate and the later sustained release rate of Ag(+) in
      the F12 medium could be more helpful for preventing implant-associated infection.
      Since the Ag-nHA/TiO(2) particles were embedded in the PA66 matrix, the long-term
      sustained release should be related both to the relaxation of PA macromolecular
      chains due to the penetration of water and to the slow release of the substituted
      Ag(+) ions in the HA lattice. The sustained Ag(+) release with time indicates
      that the composite scaffold is suitable for a long-term antimicrobial application
      during the scaffold-assisted bone repair or regeneration.

PMID- 20683128
TI  - Study of synthesis of nano-hydroxyapatite using a silk fibroin template.
AB  - Nano-hydroxyapatite (HA) was directly synthesized on a silk fibroin (SF) template
      using the property of SF being soluble in a concentrated CaCl(2) solution as a HA
      source of calcium at pH 7.4 and room temperature. The microstructure and bonding
      state were investigated by x-ray diffraction (XRD), Fourier transform infrared
      spectroscopy (FTIR), differential scanning calorimetry-thermogravimetry analysis
      (DSC-TG) and transmission electron microscopy (TEM). The results indicated that
      the HA crystals were poorly crystallized with a rod-like shape of 20-60 nm length
      and 10-20 nm diameter. Strong molecular interactions and chemical bonds might be
      present between SF and HA. There were other nucleation sites such as carbonyl (-C
      O) and amine (-N-H-) groups on SF molecules besides the carboxyl (-COOH) and
      hydroxyl (-OH) groups previously reported. During the formation of HA, the
      coordination action between specific functional groups on SF and calcium ions
      (Ca(2+)) played an important role. The crystallinity of HA was improved and had
      an orientation growth along (0 0 2) at the presence of SF, resulting in a
      structure similar to natural bone. It was concluded that SF could regulate the
      structure and morphology of HA effectively.

PMID- 20683129
TI  - Enhancement of the ALP activity of C3H10T1/2 cells by the combination of an
      oxysterol and apatite.
AB  - Biomimetic apatite coating has been used to load osteogenic biomolecules onto the
      surface of titanium implants. Apatite on the surface of biomaterials is thought
      to function as a reservoir of biomolecules as well as enhancing
      osteoconductivity. In this study, 20alpha-hydroxycholesterol (20alpha-HC), an
      osteogenic oxysterol, was used to induce differentiation of a mouse embryo
      fibroblast cell line (C3H10T1/2) by loading the oxysterol on biomimetically
      coated apatite of titanium discs. We found that the phosphatase (alkaline
      phosphatase (ALP)) activity of 20alpha-HC was significantly higher with ascorbic
      acid than alone, suggesting a need for ascorbic acid as a co-factor. When 20alpha
      HC was added into the apatite coating solution, the ALP activity of the C3H10T1/2
      cells did not increase on the apatite surface, even in the presence of ascorbic
      acid. However, ALP activity increased dramatically when 20alpha-HC was loaded by
      volatilization of EtOH from the apatite coat after dipping discs in 20alpha-HC
      dissolved EtOH. Interestingly, ascorbic acid was not needed for this increase in
      ALP activity, suggesting a synergistic effect of 20alpha-HC and apatite. The
      concentration of calcium ions, a major component of apatite, affected the
      osteogenic effect of 20alpha-HC, and the increase in ALP activity was attenuated
      by L-type calcium channel inhibitors, verapamil and nifedipine. These results
      demonstrate that calcium ions released from apatite are important in the
      synergistic effect of 20alpha-HC and apatite.

PMID- 20683130
TI  - Wear performance of self-mating contact pairs of TiN and TiAlN coatings on
      orthopedic grade Ti-6Al-4V.
AB  - Both titanium nitride (TiN) and titanium aluminum nitride (TiAlN) have shown
      great wear resistance potential in metallic medical devices as protective, hard
      thin film coatings. In the present study, the effects of TiN and TiAlN coating
      layers on the wear performance of Ti-6Al-4V were compared and analyzed. TiN and
      TiAlN coatings with a thickness of 3 microm were deposited by a cathodic vacuum
      arc ion plating technique on the surface of Ti-6Al-4V. Wear tests were conducted
      by using a pin-on-disk-type tribotester with a point contact self-mating pair in
      a linear reciprocal motion. A sliding distance of 20 mm per cycle at 1 Hz was
      used under a load of 15 N under ambient conditions with no lubricant. The wear
      resistance of TiN and TiAlN coatings is superior to that of uncoated Ti-6Al-4V at
      the early stage of sliding contact. Until a measurable amount of wear was
      detected, the number of sliding cycles of the TiAlN coating pair was longer than
      TiN. After the first detection of wear from the coating layers, the rate of wear
      of the TiN coating pairs was significantly higher than that of TiAlN (p < 0.05),
      and it was close to that of the uncoated pairs. In conclusion, the TiAlN coating
      is superior to TiN from the viewpoint of wear resistance under the test
      conditions used in this study.

PMID- 20683131
TI  - Chemical adhesion rather than mechanical retention enhances resin bond durability
      of a dental glass-ceramic with leucite crystallites.
AB  - This study aims to evaluate the effect of chemical adhesion by a silane coupler
      and mechanical retention by hydrofluoric acid (HFA) etching on the bond
      durability of resin to a dental glass ceramic with leucite crystallites. Half of
      the ceramic plates were etched with 4.8% HFA (HFA group) for 60 s, and the other
      half were not treated (NoHFA group). The scale of their surface roughness and
      rough area was measured by a 3D laser scanning microscope. These plates then
      received one of the following two bond procedures to form four bond test groups:
      HFA/cement, NoHFA/cement, HFA/silane/cement and NoHFA/silane/cement. The
      associated micro-shear bond strength and bond failure modes were tested after 0
      and 30 000 thermal water bath cycles. Four different silane/cement systems
      (Monobond S/Variolink II, GC Ceramic Primer/Linkmax HV, Clearfil Ceramic
      Primer/Clearfil Esthetic Cement and Porcelain Liner M/SuperBond C&B) were used.
      The data for each silane/cement system were analyzed by three-way ANOVA. HFA
      treatment significantly increased the surface R(a) and R(y) values and the rough
      area of the ceramic plates compared with NoHFA treatment. After 30 000 thermal
      water bath cycles, the bond strength of all the test groups except the
      HFA/Linkmax HV group was significantly reduced, while the HFA/Linkmax HV group
      showed only adhesive interface failure. The other HFA/cement groups and all
      NoHFA/cement groups lost bond strength completely, and all NoHFA/silane/cement
      groups with chemical adhesion had significantly higher bond strength and more
      ceramic cohesive failures than the respective HFA/cement groups with mechanical
      retention. The result of the HFA/silane/cement groups with both chemical adhesion
      and mechanical retention revealed that HFA treatment could enhance the bond
      durability of resin/silanized glass ceramics, which might result from the
      increase of the chemical adhesion area on the ceramic rough surface and
      subsequently reduced degradation speed of the silane coupler, rather than the
      mechanical retention of the ceramic rough surface.

PMID- 20683132
TI  - A novel basalt fiber-reinforced polylactic acid composite for hard tissue repair.
AB  - A basalt fiber (BF) was, for the first time, introduced into a poly(l-lactic
      acid) (PLLA) matrix as innovative reinforcement to fabricate composite materials
      for hard tissue repair. Firstly, BF/PLLA composites and pure PLLA were produced
      by the methods of solution blending and freeze drying. The results showed that
      basalt fibers can be uniformly dispersed in the PLLA matrix and significantly
      improve the mechanical properties and hydrophilicity of the PLLA matrix. The
      presence of basalt fibers may retard the polymer degradation rate and neutralize
      the acid degradation from PLLA. Osteoblasts were cultured in vitro to evaluate
      the cytocompatibility of the composite. An MTT assay revealed that osteoblasts
      proliferated well for 7 days and there was little difference found in their
      viability on both PLLA and BF/PLLA films, which was consistent with the alkaline
      phosphatase (ALP) activity results. A fluorescent staining observation showed
      that osteoblasts grew well on the composites. SEM images displayed that
      osteoblasts tended to grow along the fiber axis. The formation of mineralized
      nodules was observed on the films by Alizarin red S staining. These results
      suggest that the presence of basalt fibers does not noticeably affect
      osteoblastic behavior and the designed composites are osteoblast compatible. It
      is concluded that basalt fibers, as reinforcing fibers, may have promising
      applications in hard tissue repair.

PMID- 20683133
TI  - In vitro cytotoxicity and hemocompatibility studies of Ti-Nb, Ti-Nb-Zr and Ti-Nb
      Hf biomedical shape memory alloys.
AB  - The in vitro cytotoxicity and hemocompatibility of the Ti-Nb, Ti-Nb-Zr and Ti-Nb
      Hf biomedical shape memory alloys (SMAs) were investigated by cell culture (L-929
      fibroblast cell), hemolytic test and platelet adhesion test, with CP Ti as a
      reference material. The cytotoxicity test indicates that all the Ti-Nb, Ti-Nb-Zr
      and Ti-Nb-Hf SMAs show over 94% cell viability for different incubation times (2,
      4 and 7 days) in comparison with a negative control and CP Ti. The cell
      morphology observation shows good polygon-like adherent growth and proliferation
      of L-929 in the extracts of all the test samples and CP Ti. These results suggest
      excellent cytocompatibility for the Ti-Nb, Ti-Nb-Zr and Ti-Nb-Hf SMAs. The
      hemolytic test reveals that the hemolysis ratios of the Ti-Nb, Ti-Nb-Zr and Ti-Nb
      Hf alloys are far less than 5%, so they cannot give rise to acute hemolysis. The
      platelet morphology observation shows almost the same adhered platelet morphology
      and activation ratio for the test samples in comparison with CP Ti, except the Ti
      22Nb-6Hf alloy, which shows a lower activation ratio of platelets, indicating
      excellent blood compatibility. Therefore, it is proposed that the Ti-Nb, Ti-Nb-Zr
      and Ti-Nb-Hf SMAs will be candidates to replace Ti-Ni for biomedical
      applications.

PMID- 20683134
TI  - Single-step generation of fluorophore-encapsulated gold nanoparticle core-shell
      materials.
AB  - We report a simple route to produce fluorophore-encapsulated gold nanoparticles
      (AuNPs) in a single step under aqueous conditions using the fluorophore 1
      pyrenemethylamine (PMA). Different amounts of PMA were used and the resulting
      core-shell gold nanoparticles were analyzed using UV-visible absorption
      spectroscopy, fluorescence spectroscopy, and transmission and scanning electron
      microscopy. Electron microscopy analysis shows nanoparticles consisting of a gold
      nanoparticle core which is encapsulated with a lower contrast shell. In the UV
      visible spectra, we observed a significant red shift (37 nm) of the localized
      surface plasmon resonance (LSPR) absorption maximum (lambda(max)) compared to
      citrate-stabilized AuNPs of a similar size. We attribute the prominent LSPR
      wavelength shift for PMA-AuNP conjugates to the increase in the local dielectric
      environment near the gold nanoparticles due to the shell formation. This simple,
      aqueous-based synthesis is a new approach to the production of fluorophore
      encapsulated AuNPs that could be applicable in biological sensing systems and
      photonic device fabrication.

PMID- 20683135
TI  - A straightforward route to the synthesis of a surface-enhanced Raman scattering
      probe for targeting transferrin receptor-overexpressed cells.
AB  - A tumor cell targeting surface-enhanced Raman scattering (SERS) probe has been
      successfully synthesized by using p-mercaptobenzoic acid (pMBA) as both the SERS
      reporter and the conjugation agent for attaching transferrin molecules, which
      shows experimentally the targeting ability for transferrin receptor-overexpressed
      HeLa cells and exhibits strong SERS signals when being incubated inside cells. To
      prove that the uptake of such a SERS probe is through a Tf-receptor-mediated
      endocytosis process, two control experiments: (1) HeLa cells being incubated with
      the probe at 4 degrees C and (2) HeLa cells being pre-blocked with free
      transferrin at 37 degrees C, were employed. The difference of SERS intensity
      between the transferrin-overexpressed HeLa cells and transferrin-pre-blocked HeLa
      cells indicates that the probe has the potential to selectively target tumor
      cells.

PMID- 20683136
TI  - Temperature dependence of energy dissipation on NaCl(001) in non-contact atomic
      force microscopy.
AB  - The dissipative tip-sample interactions are measured by dynamic force
      spectroscopy for silicon tips on NaCl(001) in ultrahigh vacuum in the attractive
      and repulsive force regimes. Force and dissipation versus distance curves were
      obtained for different sample temperatures ranging from 35 to 285 K. Detailed
      comparison in different distance regimes shows that neither the force nor energy
      dissipation exhibits a systematic variation with sample temperature.

PMID- 20683137
TI  - Growth mechanism of GaN nanowires: preferred nucleation site and effect of
      hydrogen.
AB  - The growth mechanism of epitaxial GaN nanowires grown using particle-mediated
      chemical vapour deposition was investigated. By examining the diameter-dependent
      growth rate of GaN nanowires, we show that the kinetic reaction-limited growth of
      GaN nanowires originates from the combination of mono-nuclear and poly-nuclear
      growth rather than the Gibbs-Thompson effect. We present a generalized nucleation
      mediated growth model to describe the diameter dependence of the nanowire growth
      rate and show that the nucleation of sources occurs at the vapour/liquid/solid
      three-phase boundary. From the same model, we demonstrate that increased hydrogen
      concentration in the carrier gas reduces the supersaturation, leading to a
      reduced GaN nanowire growth rate. Our approach can be applied to other nanowire
      materials systems, and it allows the determination of the preferred nucleation
      site during nanowire growth.

PMID- 20683138
TI  - Impact of pre-concentration to covalently biofunctionalize suspended
      nanoparticles.
AB  - The effective biofunctionalization of nanoparticles is crucial for biomedical
      applications. In this study we investigated the covalent biofunctionalization of
      magnetic nanoparticles based on carbodiimide activation. An important aspect in
      the covalent biofunctionalization of nanoparticles has been neglected, namely pre
      concentration. Exploiting the electrostatic attraction forces between a protein
      and the nanoparticle surface will favor the covalent immobilization. We showed
      that low ionic strength buffers with a pH slightly lower than the pI of the
      selected biomolecules is needed to increase the yield of covalent immobilization.
      Additionally, it is demonstrated that the covalently immobilized proteins are
      bioactive, relying on a sandwich assay using gold nanoparticles as reporter
      labels.

PMID- 20683139
TI  - Enhancement of the core near-band-edge emission induced by an amorphous shell in
      coaxial one-dimensional nanostructure: the case of SiC/SiO2 core/shell self
      organized nanowires.
AB  - We report the influence of the native amorphous SiO(2) shell on the
      cathodoluminescence emission of 3C-SiC/SiO(2) core/shell nanowires. A shell
      induced enhancement of the SiC near-band-edge emission is observed and studied as
      a function of the silicon dioxide thickness. Since the diameter of the
      investigated SiC cores rules out any direct bandgap optical transitions due to
      confinement effects, this enhancement is ascribed to a carrier diffusion from the
      shell to the core, promoted by the alignment of the SiO(2) and SiC bands in a
      type I quantum well. An accurate correlation between the optical emission and
      structural and SiO(2)-SiC interface properties is also reported.

PMID- 20683140
TI  - High-performance supercapacitors using a nanoporous current collector made from
      super-aligned carbon nanotubes.
AB  - Nanoporous current collectors for supercapacitors have been fabricated by cross
      stacking super-aligned carbon nanotube (SACNT) films as a replacement for heavy
      conventional metallic current collectors. The CNT-film current collectors have
      good conductivity, extremely low density (27 microg cm(-2)), high specific
      surface area, excellent flexibility and good electrochemical stability. Nanosized
      active materials such as NiO, Co(3)O(4) or Mn(2)O(3) nanoparticles can be
      directly synthesized on the SACNT films by a straightforward one-step, in situ
      decomposition strategy that is both efficient and environmentally friendly. These
      composite films can be integrated into a pseudo-capacitor that does not use
      metallic current collectors, but nevertheless shows very good performance,
      including high specific capacitance (approximately 500 F g(-1), including the
      current collector mass), reliable electrochemical stability (<4.5% degradation in
      2500 cycles) and a very high rate capability (245 F g(-1) at 155 A g(-1)).

PMID- 20683141
TI  - Controlled synthesis of single-crystalline alpha-Fe2O3 micro/nanoparticles from
      the complex precursor of FeCl3 and methyl orange.
AB  - A facile method to prepare alpha-Fe(2)O(3) micro/nanoparticles by using the
      nanorod complex of FeCl(3) and methyl orange as precursors has been demonstrated.
      The single-crystalline alpha-Fe(2)O(3) micro/nanoparticles are successfully
      obtained by pyrolysis of the precursors at 800 degrees C for 4 h. The growth
      process of the precursor is investigated. The products are characterized by x-ray
      powder diffraction (XRD), thermogravimetry analysis (TGA), magnetization
      measurement, scanning electron microscopy (SEM) and transmission electron
      microscopy (TEM) and high-resolution TEM. The potential applications in water
      treatment and gas-sensing properties are investigated.

PMID- 20683142
TI  - Surface-enhanced Raman scattering on gold quasi-3D nanostructure and 2D nanohole
      arrays.
AB  - A new method was developed to fabricate unique gold quasi-3D plasmonic
      nanostructures on poly(dimethylsiloxane) PDMS and 2D nanohole arrays on silicon
      as surface-enhanced Raman scattering (SERS) substrates using electron beam
      lithography (EBL) with negative tone resist Ma-N 2403 and soft lithography. The
      size and shape of nanopillars fabricated by EBL were well controlled via
      different beam conditions. An enhancement factor (EF) as high as 6.4 x 10(5) was
      obtained for 4-mercaptopyridine molecules adsorbed on the gold quasi-3D
      nanostructure array on PDMS with 400 nm diameter, 100 nm spacing and 300 nm
      depth, while no enhancement was observed for the gold 2D nanohole array on
      silicon with the same diameter and spacing. The experimental results were
      confirmed by finite-difference time-domain (FDTD) calculations. Furthermore, the
      calculated total electric fields showed that the strong SERS exhibited by the
      gold quasi-3D nanostructure arrays on PDMS is due to the strong localized
      electric fields at the gold-air interface of the bottom gold nanodisc. The strong
      and reproducible SERS spectroscopy for molecules adsorbed on precisely controlled
      gold quasi-3D nanostructure arrays on PDMS makes it possible for the integration
      of SERS-active nanopatterns into microfluidic devices as chemical and biological
      sensors with molecular specificity.

PMID- 20683143
TI  - Rapid microwave hydrothermal synthesis of GaOOH nanorods with photocatalytic
      activity toward aromatic compounds.
AB  - GaOOH nanorods were synthesized from Ga(NO(3))(3) via a facile microwave
      hydrothermal method. The obtained sample was characterized by x-ray diffraction,
      N(2) sorption-desorption, UV-vis diffuse reflectance spectroscopy, transmission
      electron microscopy, electron spin resonance, and x-ray photoelectron
      spectroscopy. The results revealed that the as-synthesized sample was consisted
      of rod-like particles. It possessed a surface area of 14.3 m(2) g(-1), and a band
      gap of 4.75 eV. The photocatalytic property of GaOOH nanorods was evaluated by
      the degradation of aromatic compounds (such as benzene and toluene) in an O(2)
      gas stream under ultraviolet (UV) light illumination. The results demonstrated
      that GaOOH nanorods exhibited superior photocatalytic activity and stability as
      compared to commercial TiO(2) (P25, Degussa Co.) in both benzene and toluene
      degradation. In the extended (35 h) reaction test toward benzene, GaOOH
      maintained a high activity, and no obvious deactivation was observed. A possible
      mechanism of the photocatalysis over GaOOH is proposed.

PMID- 20683144
TI  - Controlled chattering--a new 'cutting-edge' technology for nanofabrication.
AB  - Chatters are unwanted random defects on surfaces often generated in cutting
      samples via microtome for micrographic analysis. In this work, we demonstrate
      that chatters can actually be controlled for fabrication of uniform periodic wavy
      patterns on polymethylmethacrylate surfaces. This control in chattering is
      achieved based on an oscillation cutting mechanism. Pattern sizes ranging from 30
      nm to a few micrometers are obtained by fine-tuning cutting speed and oscillating
      frequency. This simple one-step non-lithographic 'cutting-edge' technology is
      simple and robust, with no chemical reactions and by-products involved and ease
      in scaling up for long-range and large-areas patterns.

PMID- 20683145
TI  - Optical reflectivity from highly disordered Si nanowire films.
AB  - In this work we present a study of the reflectivity from highly disordered
      silicon nanowire films as a function of the wire size. Arrays of Au-catalyzed Si
      wires with length and diameter ranging from 0.15-0.2 microm and 30-50 nm up to 20
      25 microm and 200-250 nm, respectively, were grown on top of either SiO(2)(1
      microm)/Si(100) or Si(100) substrates. The integrated total reflection was
      measured in the 190-2500 nm spectral range. The results show that, increasing the
      wire size, the optical behavior of the Si wire film can be gradually tuned from
      that of an optical coating characterized by a graded effective refractive index
      to that of an ensemble of diffuse optical reflectors. In addition, we show how
      the optical analysis provides some important indications concerning the
      structural properties of the nanowires.

PMID- 20683147
TI  - Distribution of C-reactive protein and its association with cardiovascular risk
      factors in a population-based sample of Chinese.
AB  - C-reactive protein (CRP) levels vary remarkably with ethnic status. Its
      distribution and correlates should be investigated across diverse populations,
      and these were limited in a representative Chinese population. We investigated
      3133 participants aged 18-80 years in Shanghai, which were sampled using a
      randomized, stratified, multi-stage sampling method. The distribution of CRP was
      highly skewed toward a lower level. The median CRP was 0.55 mg/L (0.61 mg/L in
      males, 0.51 mg/L in females). Participants living in urban region had higher CRP
      levels than those in rural region (0.67 vs. 0.46 mg/L). CRP levels showed
      significant correlation with traditional cardiovascular risk factors, and it was
      most strongly correlated with body mass index. Multivariate logistic regression
      analyses indicated that elevated CRP (being in the top 15 percentile of CRP; CRP
      > or =2.09 mg/L) was significantly associated with obesity, hypertension,
      diabetes, low high-density lipoprotein cholesterol, high low-density lipoprotein
      cholesterol, high triglycerides and cardiovascular disease history. In
      conclusion, the distribution of CRP in adult Chinese was comparable with that of
      many other Asian populations but different from that of Western populations.
      Metabolic impairment was associated with elevated CRP, and CRP levels should be
      interpreted in conjunction with the lipid profile.

PMID- 20683148
TI  - Blood absolute T cell counts may predict 2-month treatment response in patients
      with pulmonary tuberculosis.
AB  - BACKGROUND AND OBJECTIVE: Little is known about the usefulness of lymphocyte
      subsets as early predictors of anti-tuberculosis (TB) treatment response in
      immuno-competent patients. METHODS: Among a total of 64 patients with culture
      positive pulmonary TB, 29 remained sputum smear/culture positive or had delayed
      resolution on CXR (slow responders (SR)), and 35 had sputum culture conversion to
      negative and rapid resolution on CXR (fast responders (FR)) after two months of
      anti-tuberculosis treatment. Clinical parameters and lymphocyte subsets were
      investigated. RESULTS: A larger proportion of patients in the SR group had
      cavities on CXR, bilateral lung involvement, positive acid-fast bacilli stains,
      and complaint of cough at diagnosis than those in the FR group. Absolute counts
      of CD3+ T cells (p = 0.016) and CD8+ T cells (p=0.012) at diagnosis were both
      significantly higher in the SR group. This trend was present throughout the 6
      month treatment course. Absolute T cell counts (odds ratio (OR) 1.002, 95%
      confidence interval (CI) 1.0-1.004), positive sputum acid fast bacilli stain (OR
      6.69, 95% CI 1.37-32.77) and bilateral lung involvement on CXR (OR 13.114, 95% CI
      1.87-92.14) at diagnosis were independent predictors for a slow response.
      Combining these three predictors, a prediction score (PS) could be calculated to
      display an optimal discrimination for slow response (area under the curve
      (AUC)=0.855, p < 0.001), whereas absolute T cell counts yielded the highest
      discriminative value on an individual level (AUC= 0.676, p=0.015). CONCLUSIONS: A
      higher T cell count at diagnosis in patients with TB may predict a slow response
      to two months of treatment. The calculation of a PS further increased predictive
      accuracy and performance.

PMID- 20683149
TI  - Prognostic significance of NOTCH1 and FBXW7 mutations in pediatric T-ALL.
AB  - The NOTCH signaling pathway plays important role in the development of
      multicellular organisms, as it regulates cell proliferation, survival, and
      differentiation. In adults, it is essential for the T- or B-lymphocyte lineage
      commitment. NOTCH1 and FBXW7 mutations both lead the activation of the NOTCH1
      pathway and are found in the majority of T-ALL patients. In this study, the
      mutation analysis of NOTCH1 and FBXW7 genes was performed in 87 pediatric T-ALLs
      who were treated on the ALL-BFM protocols. In 19 patients (22%), activating
      NOTCH1 mutations were observed either in the heterodimerization domain or in the
      PEST domain and 7 cases (10%) demonstrated FBXW7 mutations (2 cases had both
      NOTCH1 and FBXW7 mutations). We also analyzed the relationship of the mutation
      data between the clinical and biological data of the patients. NOTCH1 and FBXW7,
      NOTCH1 alone were found correlated with lower initial leucocyte counts which was
      independent from the sex and T- cell immunophenotype. However, NOTCH1 and FBXW7
      mutations were not predictive of outcome in the overall cohort of pediatric T
      ALLs.

PMID- 20683150
TI  - Frequency of P16INK4a and P14ARF genes methylation and its impact on bladder
      cancer cases in north Indian population.
AB  - INTRODUCTION: Amongst the genitourinary cancers, carcinoma of the urinary bladder
      is one of the leading causes of death in India. Hypermethylation of the CpG
      islands of gene promoter is one of the earliest and most frequent epigenetic
      alterations leading to cancer as well as in its development. Several studies have
      suggested that tumour suppressor genes play a key role in the development of
      cancer. Methylation in the CDKN2A has been associated with various malignant
      diseases, but information with respect to urinary bladder cancer is lacking in
      north Indian population. MATERIALS AND METHODS: We analyzed the methylation of
      P16INK4a and P14ARF in 80 tissues and matched blood samples of patients suffering
      from bladder cancer and 80 blood samples of cancer-free individuals by MS-PCR.
      RESULTS: In tissue and matched blood samples of bladder cancer patients, the
      incidence of P14ARF hypermethylation significantly increased (OR=0.31, 95%CI
      =0.12-0.8, P=0.01) and (OR=0.0, 95%CI=0.0-0.62, P=0.006) respectively with an
      increase in age. Clinicopathological analysis revealed that P14ARF
      hypermethylation in tissue and blood samples was significantly associated with
      invasive stage (> or =T2) (OR=0.21, 95%CI = 0.08-0.51, P=0.0002) and (OR = 0.09,
      95%CI = 0.03-0.37, P= 0.00001) respectively. Muscle invasive tumour stage (> or
      =T2) showed significant association with increased risk of P16INK4alpha promoter
      hypermethylation in tissue and blood samples of patients (OR = 0.38, 95%CI = 0.17
      0.82, P= 0.01) and (OR = 0.13, 95%CI = 0.05-0.36, P= 0.00005) respectively.
      CONCLUSION: These results suggest that the CpG island hypermethylation status of
      the defined panel of genes may be a useful biomarker in patients suffering from
      bladder cancer.

PMID- 20683151
TI  - Genetic polymorphism of glutathione S transferases M1 and T1 in Indian patients
      with hepatocellular carcinoma.
AB  - OBJECTIVE: Our aim was to evaluate whether the association of GSTM1/T1 gene
      polymorphisms modifies the risk of Hepatocellular carcinoma (HCC) and what is its
      correlation with other predisposing risk factors like alcohol intake, cigarette
      smoking and hepatitis B and C infections. STUDY DESIGN/SETTING: It was a case
      control study, included 254 HCC cases compared with 525 hospital-based age and
      sex matched cases of chronic liver disease without HCC as controls from Indian
      population. The GSTM1 and GSTT1 genotypes were detected using conventional
      multiplex PCR method. RESULTS: In this case-control study, we observed a positive
      correlation between age, HBV and HCV infection, smoking habit of > 20 packs/year,
      alcohol consumption of > 100 g/day and risk of liver cancer. We found
      significantly increased risk associated with GSTM1 null genotype (OR = 3.49; 95%
      CI = 2.52-4.84) as well as GSTT1 null genotype (OR = 3.12; 95% CI = 2.19-4.45),
      respectively. However, an increased risk of HCC was observed among heavy drinkers
      with GSTM1 (OR = 2.01; 95% CI = 1.11-3.66). Further, cigarette smoking showed a
      non-significant association with GSTT1 (OR = 1.49; CI = 0.69-3.25). CONCLUSION:
      Our results suggest that the variants in low penetrance gene such as GSTM1 and
      GSTT1 are associated with an increased liver cancer risk. Further, an influence
      of GSTM1/T1 null genotypes may contribute in the etiology of HCC in patients with
      higher cigarette and alcohol consumption.

PMID- 20683152
TI  - BRCA1 and BRCA2 germline mutations screening in Algerian breast/ovarian cancer
      families.
AB  - BACKGROUND: Breast cancer is the leading cause of cancer death in women in
      Algeria. The contribution of BRCA1 and BRCA2 mutations to hereditary
      breast/ovarian cancer in Algerian population is largely unknown. Here, we
      describe analysis of BRCA1 and BRCA2 genes in 86 individuals from 70 families
      from an Algerian cohort with a personal and family history suggestive of genetic
      predisposition to breast cancer. METHODS: The approach used is based on BRCA1 and
      BRCA2 mutations screening by High-Resolution Melting (HRM) curve analysis
      followed by direct sequencing. All samples for which no pathogenic mutation was
      found were analyzed by MLPA for large deletions or duplications. RESULTS: Three
      distinct pathogenic mutations c.83_84delTG, c.181T>G, c.798_799delTT and two
      large rearrangements involving deletion of exon 2 and exon 8 respectively, were
      detected in BRCA1 gene. Moreover 17 unclassified variants and polymorphisms were
      detected in BRCA1 gene (6 described for the first time). Two pathogenic
      mutations, c.1310_1313delAAGA and c.5722_5723delCT and 40 unclassified variants
      and polymorphisms (14 never described before) were identified in BRCA2 gene.
      CONCLUSIONS: For the first time, we used HRM and MLPA to identify BRCA1 and BRCA2
      mutations in Algerian patients with a personal and family history suggestive of
      genetic predisposition to breast cancer. The implications of these new findings
      in regard to genetic testing and counseling are substantial for the Algerian
      population.

PMID- 20683153
TI  - Conflicting views on the molecular structure of the cancer antigen CA125/MUC16.
AB  - CA125 is a tumor antigen used to monitor the progression and regression of
      epithelial ovarian cancer. Despite the widespread use of CA125, the biochemical
      and molecular nature of this antigen is poorly understood. Analysis of the
      structure of CA125 is essential for determining the physiological role of this
      very significant tumor marker. Accumulated experimental evidence has shown that
      CA125 epitopes reside on a molecule of very complex architecture in terms of both
      protein backbone and oligosaccharide structures. It is not clear whether the
      heterogeneity of CA125 molecular characteristics are due to the variability of
      biological sources from which the molecule was isolated or to the different
      biophysical methods used for the characterization of all the oligosaccharides
      linked to CA125 or to the presence of glycoisoforms for this protein. This review
      attempts to summarize emerging data related to molecular characteristics of CA125
      and to compare approaches undertaken to reach a better understanding of molecular
      features of this tumor marker.

PMID- 20683154
TI  - Hemorheological alterations related to training and overtraining.
AB  - Alterations of blood rheology related to muscular activity have been extensively
      studied over the last 20 years. It has been shown that exercise exerts a
      "triphasic" action on the rheological properties of blood. In the short term,
      exercise induces a transient hyperviscosity, mostly due to a rise in hematocrit
      and plasma viscosity, but also to alterations in erythrocyte rheology. Reversal
      of this hyperviscosity pattern over the following 24 h can be described as an
      "autohemodilution". Later, training results in several profiles of "hemorheologic
      fitness" with a low hematocrit reflecting an expansion in plasma volume, and
      improvements in red cell rheology (increased deformability, decreased
      aggregation, reduced disaggregation shear rate). Some specific aspects of these
      long-term adaptations have been described, such as the intriguing occurrence of a
      paradoxical improvement in RBC deformability during exercise in some athletes,
      and overtraining, which is associated with higher plasma viscosity. Given the
      variety of modes of exercise and the wide heterogeneity of their effects on blood
      rheology in the short and long term, many investigations remain to be performed
      in this area of clinical hemorheology.

PMID- 20683155
TI  - A full-range, multi-variable, CFD-based methodology to identify abnormal near
      wall hemodynamics in a stented coronary artery.
AB  - The benefit of coronary stent implantation is reduced by excessive intimal
      hyperplasia which re-narrows the artery and the prevention of which is still a
      primary concern for clinicians. Abnormal hemodynamics create non-physiological
      viscous stress on the artery wall, one of the root causes of intimal hyperplasia
      following stent implantation. A methodology to comprehensively evaluate the
      viscous stress on the artery wall following stent implantation would be useful to
      evaluate a stent's hemodynamic performance.The proposed methodology employs 3D
      computational fluid dynamics, the variables wall shear stress (WSS), WSS gradient
      (WSSG), WSS angle gradient (WSSAG) and a statistical analysis to evaluate the
      viscous stress. The methodology is demonstrated and compared to a commonly used
      "threshold technique" for evaluating a stent's hemodynamic performance.It is
      demonstrated that the threshold technique is not adequate to fully analyse the
      viscous stress on the artery wall and can even be misleading. Furthermore, all
      three of the aforementioned variables should be considered as each provides a
      different perspective on the abnormalities that can arise in the arterial viscous
      stress.The hemodynamic performance of a stent can be assessed more
      comprehensively than with previously used methods by examining the arterial
      viscous stresses using the proposed methodology.

PMID- 20683156
TI  - Viscoelastic properties of liver measured by oscillatory rheometry and
      multifrequency magnetic resonance elastography.
AB  - The mechanical properties of liver can sensitively indicate the progression of
      hepatic fibrosis. Mechanical tissue characterization involves the analysis of the
      complex shear modulus measured either by oscillatory rheometry or by in vivo
      elastography. In this study, bovine liver specimens were investigated by
      oscillatory rheometry and multifrequency magnetic resonance elastography (MRE) in
      a common frequency range between 25.0 and 62.5 Hz. The results were compared with
      in vivo MRE of human liver. Storage and loss moduli were quantified, and the data
      were also analyzed employing a springpot model, yielding a stiffness-related
      parameter of 2.96+/-0.53 kPa in bovine liver by rheometry and of 2.20+/-0.45 kPa
      in human liver by in vivo MRE. Furthermore, MRE of excised bovine liver showed
      that stiffness tended to increase with decreasing sample temperature. In
      conclusion, mechanical tissue characterization by multifrequency MRE agrees well
      with oscillatory rheometry, which validates MRE as a method for investigating the
      rheology of liver tissue.

PMID- 20683157
TI  - Analysis of power law models for the creep of nucleus pulposus tissue.
AB  - Tissue engineering approaches are now being investigated for altering the course
      of intervertebral disc degeneration (IDD). Because the disease changes the
      mechanical properties of the load bearing tissues of the disc, viscoelastic
      tissue behavior is a key measure for comparing the efficacy of treatments. To
      investigate the basic viscoelastic behavior of nucleus pulposus tissue, tissue
      from the rabbit disc was tested in torsional creep. Both the Andrade and Nutting
      creep models had a good fit to the data, however, the Andrade creep model gave a
      much better prediction of the longer term creep. This is the first application of
      Andrade creep to biological tissue and results indicate that this model may be
      particularly well suited for characterizing the viscoelastic behavior of very
      soft biological tissues.

PMID- 20683158
TI  - An in vitro method for screening anti-platelet agents using a microchannel array
      flow analyzer.
AB  - New in vitro methods are desirable for the analysis of platelet aggregation and
      screening novel anti-platelet agents using whole blood. To this end, we examined
      platelet aggregation and thrombus formation in whole human blood from healthy
      volunteers using a microchannel array flow analyzer (MC-FAN). Platelet
      aggregation in whole blood, treated with the activating agents ADP, collagen or
      ristocetin was detected in the MC-FAN by measuring the decrease in flow rate as a
      function of agent concentration. The results were compared with aggregation in
      platelet rich plasma (PRP) in a conventional aggregometer, as measured by the
      increase in optical density. The MC-FAN detected platelet aggregation in whole
      blood at two- to four-fold lower concentrations of agonist compared to those in
      PRP in the aggregometer. Anti-platelet agents attenuated the decrease in blood
      flow rate in the MC-FAN by inhibiting fibrin formation and platelet aggregation,
      but anticoagulants only inhibited fibrin formation and did not affect blood flow
      rates. These findings suggest that the MC-FAN system may be a useful method for
      the evaluation of platelet activation and facilitate the development of novel
      anti-platelet agents.

PMID- 20683160
TI  - Roles for occupational therapists and physiotherapists.

PMID- 20683161
TI  - Development of roles for occupational therapists and physiotherapists in work
      related practice: An Australian perspective.
AB  - OBJECTIVE: This paper will explore the development of occupational therapists'
      and physiotherapists' roles in work related practice from an early focus on
      rehabilitation of injured workers, to one including prevention and health
      promotion. METHODS: A review of international evidence identified the roles,
      tasks and employment paths for occupational therapists and physiotherapists in
      work related practice. The relationship between government regulation and
      therapists' access to the workplace was also examined. RESULTS: Occupational
      therapists and physiotherapists hold valued positions in work related
      professional practice. Whilst initially their roles were based on injury
      management through occupational rehabilitation, both professions have
      demonstrated a clear vision of the importance of prevention of work related
      injury and disease. Social and workplace changes in the late 1970s in a number of
      western countries, commencing with the Robens' reforms in the United Kingdom, led
      to improved legislation and regulation for managing occupational health and
      safety. CONCLUSIONS: The approach of both disciplines to practice in this field
      reflects their individual professional education. However, some role overlaps
      exists in consultancy activities in the industrial environment. Implementation of
      modern OHS regulatory programs in other western countries, including Australia,
      has increased and broadened the opportunities for therapists, as governments,
      employers and insurers support early intervention to minimise the impact of
      workplace injuries and diseases.

PMID- 20683162
TI  - Focus on health, motivation, and pride: A discussion of three theoretical
      perspectives on the rehabilitation of sick-listed people.
AB  - OBJECTIVE/METHOD: During the last decades sickness absence from work has become a
      great societal problem. Questions of how rehabilitation processes should become
      successful and how peoples' ability to work can be improved have become of great
      public interest. In this paper we discuss three well-known theoretical
      perspectives regarding their usefulness when it comes to research on
      rehabilitation for return to work. RESULTS: The three perspectives are:
      Antonovsky's salutogenic model of health, Kielhofner's model of human occupation
      and Scheff's sociological theory of "shame and pride". CONCLUSIONS: Each of these
      can be applied to increase understanding and knowledge concerning sickness
      absence and return to work. We discuss points of affinity among the three
      perspectives, as well as significant differences, and we propose that a very
      essential common denominator is the importance of self-experience.

PMID- 20683163
TI  - Methods for analysing individual changes in sick-leave diagnoses over time.
AB  - Several methodological challenges arise when attempting to analyse individual
      data on changes of sick-leave diagnoses over several years. Sick-leave spells for
      a person can recur, have different sick-leave diagnoses, and both these aspects
      are dependent of previous episodes, the numbers of repeated periods vary across
      subjects, and standard statistical methods are not valid for variables on nominal
      scales, e.g. sick-leave diagnoses. OBJECTIVE: Our aim was to ascertain whether
      the number and pattern of changes in sick-leave diagnoses are associated with
      future disability pension (DP) and to test methods for analysis of repeated
      measurements on nominal data. PARTICIPANTS: Data from a 12-year prospective
      cohort study of the 8000 sick-leave periods of the 213 persons aged 25-34 who, in
      1985, had a new sick-leave spell 28 days with back diagnoses were used. METHODS:
      We used entropies, uncertainty coefficients adjusted for repeated measurements,
      and transition matrices to examine the changes in sick-leave diagnoses that
      occurred during follow up. RESULTS: In the 12 years 22% were granted DP and they
      had changed sick-leave diagnosis less frequently and more often had new sick
      leave periods with musculoskeletal diagnoses than the others. The variation in
      diagnoses and the degree of dependence between consecutive diagnoses were
      associated with DP. CONCLUSIONS: Many tools in statistics are based on linear
      methods that require numerical variables, but such methods are not valid for
      repeated measurements on discrete variables on nominal scales, as for sick-leave
      diagnosis. In such cases, it can be beneficial to use tools that are applied in
      statistical information theory.

PMID- 20683164
TI  - Influence of weight loss on musculoskeletal pain: Potential short-term relevance.
AB  - OBJECTIVE: With the recent trend of increasing obesity in the United States, more
      immediate health outcomes such as reduced musculoskeletal pain may be more
      effective in encouraging compliance. The study objective was to investigate the
      relationship between weight loss and changes in musculoskeletal pain.
      PARTICIPANTS: Thirty-five females who recently enrolled into a weight loss
      program were enrolled into the study. METHODS: The impact of weight loss on
      musculoskeletal pain in the short-term was assessed by tracking pain and weight
      loss during bi-weekly visits to a weight loss clinic. During a 12-week
      prospective study, the pain ratings in 9 body regions measured during the bi
      weekly weigh-ins at the clinic. RESULTS: A significant association was found
      between weight loss and reduction of pain in the elbow, upper back, lower back,
      and hip regions as well as overall pain. CONCLUSIONS: The significant trends
      between weight loss and corresponding reduction in pain provide support to weight
      loss management providers that may have more immediate relevance - a quick impact
      on pain may encourage compliance with weight loss programs. While the trends for
      weight and pain are intriguing, future research will need to indentify the
      underlying mechanism for the reduced pain. One potential mechanism may be that a
      reduction of weight reduces the biomechanical stress on the load bearing joints,
      reducing pain responses.

PMID- 20683165
TI  - Learning in the workplace: Fostering resilience in disengaged youth.
AB  - OBJECTIVE: International reports on school-to-work transition make it clear that
      worldwide youth are at-risk for educational disengagement and are three times as
      likely to be unemployed as their adult counterparts. Work-based education (WBE)
      is one of the most frequently recommended solutions for youth disengagement which
      suggests that WBE serves as a protective factor and encourages resilience in at
      risk youth. The objective of this study was to describe and compare the
      experiences of two at-risk youth enrolled in WBE. PARTICIPANTS: Two 18-year old
      at-risk youth enrolled in WBE were chosen for study because they were learning in
      workplaces judged likely to promote resilience. Both had been disengaged from
      school prior to enrolling in WBE. METHOD: Each multiple-perspective case study
      includes the perspective of the youth, the workplace employer, and the work-based
      educator. Data consisted of ethnographic observations and interviews conducted at
      the workplace, and with the teacher in the school. RESULTS: Each case study
      highlights how supportive adults and an at-risk youth engage in interactions that
      facilitate the emergence of resilience in the workplace. CONCLUSIONS: In these
      two cases, risk and resilience are context specific, suggesting that at-risk
      youth may require tailored workplace programs to meet their career development
      needs.

PMID- 20683166
TI  - Dancing the two-step: Collaborating with intermediary organizations as research
      partners to help implement workplace health and safety interventions.
AB  - OBJECTIVE: To evaluate the effect of the involvement of intermediaries who were
      research partners on three intervention studies. The projects crossed four
      sectors: manufacturing, transportation, service sector, and electrical-utilities
      sectors. The interventions were participative ergonomic programs. The study
      attempts to further our understanding of collaborative workplace-based research
      between researchers and intermediary organizations; to analyze this collaboration
      in terms of knowledge transfer; and to further our understanding of the successes
      and challenges with such a process. PARTICIPANTS: The intermediary organizations
      were provincial health and safety associations (HSAs). They have workplaces as
      their clients and acted as direct links between the researchers and workplaces.
      METHODS: Data was collected from observations, emails, research-meeting minutes,
      and 36 qualitative interviews. Interviewees were managers, and consultants from
      the collaborating associations, 17 company representatives and seven researchers.
      RESULTS: The article describes how the collaborations were created, the structure
      of the partnerships, the difficulties, the benefits, and challenges to both the
      researchers and intermediaries. The evidence of knowledge utilization between the
      researchers and HSAs was tracked as a proxy-measure of impact of this
      collaborative method, also called Mode 2 research. CONCLUSION: Despite the
      difficulties, both the researchers and the health and safety specialists agreed
      that the results of the research made the process worthwhile.

PMID- 20683167
TI  - A sub-maximal occupational aerobic fitness test alternative, when the use of
      heart rate is not appropriate.
AB  - Several emergency response organisations have introduced a minimum aerobic
      fitness test to predict performance on critical tasks, as well as to help ensure
      some protection against the cardiovascular stress associated with emergency
      situations. A popular indirect sub-maximal test of aerobic fitness is the step
      test; this test relies on the relationship between exercise intensity, heart rate
      and aerobic capacity. This relationship, and the tests that rely on it, are not
      valid for individuals who are on prescribed medication (often for high blood
      pressure) that alter the heart rate response to exercise. OBJECTIVE: The purpose
      of the work described in this paper was to develop a sub-maximal test of aerobic
      fitness that did not rely on heart rate. PARTICIPANTS AND METHODS: Eighty-four
      subjects undertook the Tecumseh step test and a six-minute maximal walk test.
      RESULTS: A Pearson Product correlation of r=- 0.81, P< 0.01 was identified
      between the distance that an individual could walk in six minutes and their heart
      rate response to the step test. CONCLUSIONS: It is concluded that the walk test
      offers a valid alternative to the step test for the indirect sub-maximal
      assessment of aerobic fitness.

PMID- 20683168
TI  - Personal Assistance Services (PAS) for individuals with disabilities: self-care
      at the workplace.
AB  - OBJECTIVE: The intent of this investigation was to identify current definitions,
      issues, and strategies related to the use of Personal Assistance Services (PAS)
      in the workplace. PARTICIPANTS: The participants were employees with disabilities
      who used PAS in the workplace as well as employers who participated in research
      studies over the past 20 years. METHODS: More than 30 articles were reviewed to
      determine PAS definitions, use, policies, and outcomes. A comprehensive search of
      bibliographic resources (e.g., EBSCOhost) was conducted to identify appropriate
      articles. RESULTS: The articles revealed current definitions of workplace PAS,
      demonstrated an increasing need for PAS, and highlighted fiscal and societal
      barriers to the full implementation of PAS at work. CONCLUSIONS: The outcomes
      clarify the historical components, but also identify questions that remain. These
      questions concern the effectiveness of PAS, best practices for funding PAS, and
      the need for national and local policies to support the use of PAS for workers
      with disabilities.

PMID- 20683169
TI  - An ergonomic approach to reorganize parking inspection agents' work productivity,
      health and safety in Sao Paulo, Brazil.
AB  - OBJECTIVE: The Traffic Engineering Company of the City of Sao Paulo (Brazil)
      observed a decrease in productivity, and an increase in sick leave, accidents and
      psychological distress among their parking inspection agents. To document this
      situation, qualitative research was undertaken to obtain an in-depth
      comprehension of work activity. PARTICIPANTS: Workers, managers and health and
      safety professionals contributed to the documentation of the problem and to the
      proposal of possible solutions. METHODS: Ergonomic work analysis focusing on real
      work activity, as well as interviews with individual or groups of stakeholders,
      were conducted. RESULTS: This research revealed that political-economic factors
      gradually contributed to: 1) an increasing work load; 2) growing fatigue
      throughout the day, increasing the workers' vulnerability to incidents and
      accidents and their tendency to react inappropriately to violence experienced on
      the street; and 3) excessive individual responsibility to manage dangerous
      situations. CONCLUSIONS: Recommendations to ameliorate the situation are
      proposed. These suggestions are discussed in terms of feasibility given the
      impact of macro social factors upon micro work activity, and the associated
      potential expansion of the ergonomist's role.

PMID- 20683170
TI  - Understanding legislation and case law - Evidence informed decision-making for
      Canadian occupational therapists in workplace-based practise.

PMID- 20683171
TI  - Differential Item Functioning in rehabilitation research.
AB  - Measurement is critical to Rehabilitation practice and research. To provide
      effective services and to have valid research results, it is imperative to have
      valid and reliable assessment tools. Differential Item Functioning (DIF) is a
      statistical procedure which better enables us to assess both the validity and the
      results of measurement instruments. As such, it is a methodology that can be very
      beneficial to the field of Rehabilitation. The purposes of this article are to
      (a) explain the fundamental principles and components of DIF, (b) discuss the
      practical implications of DIF for the Rehabilitation discipline, and (c) provide
      an example of DIF implementation and interpretation of results.

PMID- 20683172
TI  - Short term effects of levothyroxine treatment in thyroid multinodular disease.
AB  - The levothyroxine suppressive efficacy in benign thyroid nodules treatment is
      well described in uninodular non-toxic goiter, whereas only few controlled trials
      enrolled patients with multinodular disease. The aim of the present study is to
      evaluate the short term effects of levothyroxine treatment in never treated, pre
      menopausal women affected by thyroid multinodular disease. Seventy-one pre
      menopausal women with thyroid multinodular disease, still presenting normal TSH
      levels, from Latina area were randomly assigned to a levothyroxine treated or
      control group. Biochemical and ultrasonography evaluations of thyroid were
      monitored at the enrollment and after 6, 12 and 24 months of treatment. In the
      levothyroxine treated group, after 1 year of treatment, thyroid and dominant
      nodule volume and number of nodules >0.5 mL significantly decreased from a median
      of 12.0 to 9.8 mL (p <0.001), from 1.0 to 0.5 mL (p <0.001) and from 0.5 to 0,
      respectively. Conversely, in the control group significant augmented values of
      these parameters were observed (p =0.007, p <0.001 and p <0.001, respectively).
      Furthermore, these observations were also confirmed by results obtained after a
      24 months follow-up period. Our data support previous observations on the
      clinical usefulness of L-T(4) treatment in preventing thyroid and nodule volume
      and nodule numbers growth. These findings confirm the tendency of benign nodular
      disease toward progression and the efficacy of TSH suppression in preventing its
      evolution by means of removing the major growth factor for thyroid nodules still
      responsive to physiological stimuli.

PMID- 20683173
TI  - Orlistat and L-carnitine compared to orlistat alone on insulin resistance in
      obese diabetic patients.
AB  - Our study wants to evaluate the effects of one year treatment with orlistat plus
      L-carnitine compared to orlistat alone on body weight, glycemic and lipid
      control, and insulin resistance state in type 2 diabetic patients. Two hundred
      and fifty-eight patients with uncontrolled type 2 diabetes mellitus (T2DM)
      [glycated hemoglobin (HbA(1c)) > 8.0%] in therapy with different oral
      hypoglycemic agents or insulin were enrolled in this study and randomised to take
      orlistat 120 mg three times a day plus L-carnitine 2 g one time a day or orlistat
      120 mg three times a day. We evaluated at baseline, and after 3, 6, 9, and 12
      months these parameters: body weight, body mass index (BMI), HbA(1c), fasting
      plasma glucose (FPG), post-prandial plasma glucose (PPG), fasting plasma insulin
      (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), total
      cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density
      lipoprotein-cholesterol (HDL-C), triglycerides (Tg), retinol binding protein-4
      (RBP-4), resistin, visfatin, high sensitivity-C reactive protein (Hs-CRP). We
      observed a faster, and better decrease of body weight, HbA(1c), FPG, PPG, LDL-C,
      HOMA-IR with orlistat plus L-carnitine compared to orlistat. A faster improvement
      of TC, Tg, FPI, resistin, RBP-4, visfatin, and Hs-CRP was reached with orlistat
      plus L-carnitine compared to orlistat. We can safely conclude that the
      association of orlistat plus L-carnitine was better than orlistat in improving
      body weight, glycemic and lipid profile, insulin resistance, and inflammatory
      parameters and no significant adverse events were recorded.

PMID- 20683174
TI  - Dietary glycemic index, glycemic load and blood lipid levels in middle-aged
      Japanese men and women.
AB  - AIMS: This study investigated the association between dietary glycemic index
      (GI)/glycemic load (GL) and serum lipids in middle-aged Japanese men and women.
      METHODS: The study participants were employees of a metal products factory in
      Japan: 2,257 men and 1,598 women aged 35 years or older. Dietary GI and GL were
      assessed using a self-administered diet history questionnaire. Serum lipid
      levels, adjusted for age, body mass index, alcohol consumption, smoking, physical
      activity, menopause status, and dietary intake of total energy, saturated fatty
      acids, monounsaturated fatty acids, polyunsaturated fatty acids, cholesterol and
      fiber, were compared among GI/GL quintiles for each gender. RESULTS: No
      significant associations were observed between GI and adjusted serum lipids in
      men or women. In contrast, GL was inversely associated with HDL-cholesterol in
      men and women (p for trend=0.001 for men and < 0.001 for women), and positively
      associated with non-HDL-cholesterol (p for trend=0.010), LDL-cholesterol (p for
      trend=0.035) and triglycerides (p for trend=0.011) in women; however, alcohol
      drinking affected these associations; there was no association between GL and
      serum lipids in male nondrinkers and between GL and LDL-cholesterol in female
      nondrinkers. CONCLUSION: GL was inversely associated with HDL-cholesterol and
      positively associated with non-HDL-cholesterol in Japanese women. These
      associations in men were not observed in nondrinkers. A high-GL diet for women
      may have an atherogenic effect through these serum lipid abnormalities.

PMID- 20683175
TI  - What is the optimum minimum segment size used in step and shoot IMRT for prostate
      cancer?
AB  - Although the use of small segments in step and shoot IMRT provides better dose
      distribution, extremely small segments decrease treatment accuracy. The purpose
      of this study was to determine the optimum minimum segment size (MSS) in two-step
      optimization in prostate step and shoot IMRT with regard to both planning quality
      and dosimetric accuracy. The XiO treatment planning system and Oncor Impression
      Plus were used. Results showed that the difference in homogeneity index (HI),
      defined as the ratio of maximum to minimum doses for planning target volume,
      between the MSS 1.0 cm and 1.5 cm plans, and 2.0 cm plans, was 0.1%, and 9.6%,
      respectively. With regard to V107 of PTV, the volume receiving 107% of the
      prescribed dose of the PTV, the difference between MSS 1.0 cm and 1.5 cm was 2%.
      However, the value of the MSS 2.0 cm or greater plans was more than 2.5-fold that
      of the MSS 1.0 cm plan. With regard to maximum rectal dose, a significant
      difference was seen between the MSS 1.5 cm and 2.0 cm plans, whereas no
      significant difference was seen between the MSS 1.0 cm and 1.5 cm plans.
      Composite plan verification revealed a greater than 5% dose difference between
      planned and measured dose in many regions with the MSS 1.0 cm plan, but in only
      limited regions in the MSS 1.5 cm plan. Our data suggest that the MSS should be
      determined with regard to both planning quality and dosimetric accuracy.

PMID- 20683176
TI  - Comparative susceptibility of some avian and mammalian lymphoblastoid cell lines
      to chicken anemia virus.
AB  - Although MSB1 is the most-commonly used lymphoblastoid cell line for isolation of
      chicken anemia virus (CAV), some researchers have reported a few biological
      drawbacks. None of them were supported by the results of the present study.
      Another four avian (HP1, HP2, BK3 and CU10) and two mammalian (BTL-26 and KO-1)
      cell lines were investigated for susceptibility to the TK-5803 and AH-9409
      strains. Both strains caused CPE on BK3 like MSB1. The mean number of positive
      cells for each strain in MSB1 and BK3 were not significantly different. The
      majority of the HP2, CU10 and HP1 cells showed no CPE. The virus titers of both
      strains were higher in MSB1 and BK3 (10(6.5-7.5) TCID(50)/0.1 ml) than in HP2,
      CU10 and HP1 (10(3.5-4.5) TCID(50)/0.1 ml). BTL-26 and KO-1 were resistant to
      CAV. BK3 could be used for isolation of CAV.

PMID- 20683178
TI  - Unmet needs of people with developmental and intellectual disability.

PMID- 20683179
TI  - Perspectives of intellectual disability in South Africa: epidemiology, policy,
      services for children and adults.
AB  - PURPOSE OF REVIEW: This review aims to summarize data published in the scientific
      literature and available on official websites on the epidemiology, policies and
      services for children and adults with intellectual disability in South Africa.
      RECENT FINDINGS: There is a paucity of published literature on intellectual
      disability in South Africa. The lack of evidence-based publications within the
      prescribed review period of 12-18 months precludes an accurate description of the
      prevailing epidemiology and burden of disablement in this country. The few
      studies yielding epidemiological data were conducted prior to 2002. These suggest
      that the prevalence rate of intellectual disability is greater than in high
      income countries. There is little data describing intellectual disability
      geographically and across population and age groups, further rendering it
      difficult to identify inequalities and differences in distribution. There is a
      high burden of preventable causes of intellectual disability. SUMMARY: Despite
      the existence of policies and services for the population with intellectual
      disabilities in South Africa, recognition of and provision for their needs
      carries low priority. It is imperative that the information gap in epidemiology
      and the burden of disability be recognized in order to plan for and meet the
      needs of those with intellectual disability across the lifespan.

PMID- 20683180
TI  - Objectivity and ethics in forensic psychiatry.
AB  - PURPOSE OF REVIEW: In this paper, we analyze the concept of objectivity as it is
      accepted in the 'standard position' on ethical practice in forensic psychiatry
      and confront it with the current trends of psychiatric nosology, specially the
      debate that we have now regarding the theoretical orientation of DSM-5, which is
      intended to be more based on neuroscientific more than on clinical data, as has
      been the tradition in psychiatry so far. RECENT FINDINGS: In view of those
      elements, we review the skeptical position about the ethics of forensic
      psychiatry and the obstacles that, in my opinion, are still standing according to
      Stone's proposal: the fact-value distinction, determinism vs. free will, the
      deconstruction of the self, the mind-brain problem, and the chasm between
      morality and normal science. In my opinion the objections made by Stone on the
      feasibility of forensic psychiatry in the courts continue in full force, to the
      extent that these objections are the heart of the debate about the theoretical
      orientation of the DSM-5. SUMMARY: The advocates of the standard position have an
      overly optimistic view of the capacity of objectification of forensic psychiatry.
      This problem has also been revealed in the intense debates on the direction of
      the DSM-5 in general psychiatry, a draft of which appears excessively based on
      neuroscience and little on traditional clinical practice.

PMID- 20683181
TI  - Insane defendants and forensic convicts: before and after the onset of the new
      forensic psychiatry network and the criminal justice system reform in Chile.
AB  - PURPOSE OF REVIEW: Like other Latin American democratic societies, Chile is
      supposed to respect legal rights of mentally ill people who are in trouble with
      the law, and provide them protection, treatment and welfare. Therefore, in this
      decade, the Chilean Criminal Justice and Mental Health System has undergone
      significant changes. RECENT FINDINGS: Because this article is related to the
      recent social features that involve different areas such as justice, mental
      health assistance and forensic psychiatry systems, and thereby the nonexistence
      of current literature that reviews this matter from a global perspective and its
      implications for the mental health population involved in the justice system, its
      review and analysis seems to be interesting. SUMMARY: The 'New Forensic
      Psychiatry Network' (NFPN) has been putting in relevant efforts to offer proper
      treatment and forensic assessment taking into account the civil rights of
      mentally insane people, and the 'Criminal Justice System Reform' (CJSR) is making
      possible legal conditions for better justice ensuring a more just resolution of
      insane defendants' and mentally ill convicts' lawsuits. From the author's
      viewpoint, all these changes are leading to a deep cultural impact on a Chilean's
      mind, changing their vision of justice and how society should respect insane
      defendants' and mentally ill convicts' legal rights.

PMID- 20683182
TI  - Forensic psychiatry in some Balkan countries.
AB  - PURPOSE OF REVIEW: In Balkan countries, as in all Europe, forensic psychiatry as
      a subspecialty between psychiatry and legal medicine, an interface between mental
      health and the law, is focused on assessment and treatment of people with mental
      disorder who show antisocial or violent behavior. Thus, the authors thought that
      to show the actual situation of forensic psychiatry in their countries would be
      more interesting than only to review some articles published in these last 2
      years in this part of the world. RECENT FINDINGS: The article also includes some
      review about forensic psychiatry in prison in Bulgaria, Serbia and Russia and
      about a recent book published in Bulgaria. SUMMARY: After a brief history of
      forensic psychiatry in some Balkan countries, the authors describe the services,
      the high and medium secure units found in forensic hospitals or in general
      psychiatry hospitals, which are still limited, where mentally disordered
      offenders are treated. Because of our society's values, individual freedom and
      civil liberties, questions about the right to treatment (or the right to refuse
      treatment), involuntary hospitalization, and other legal and ethical issues have
      no easy answers. Ethical questions remain in dispute, like patient's needs vs.
      social needs and human rights, legality vs. morality.The quality standards must
      be improved, especially those concerning elementary care needs and quality of
      life of forensic psychiatry patients (accommodation, food, sheltered housing,
      sheltered work places and community involvement). Ways will be found to protect
      human rights and avoid any abuse of psychiatry.

PMID- 20683183
TI  - Current world literature.

PMID- 20683184
TI  - Neuroimaging enrichment strategy for secondary prevention trials in Alzheimer
      disease.
AB  - We examined the improvement in statistical power that could be obtained in
      therapeutic trials for early (predementia) Alzheimer disease by constraining
      enrollment to individuals with amnestic mild cognitive impairment (MCI) and an
      atrophy pattern on a screening magnetic resonance imaging (MRI) scan previously
      found to be predictive of clinical decline, or to individuals with MCI and the
      apolipoprotein E epsilon 4 genetic risk factor for Alzheimer disease. Treatable
      effects were defined as absolute change versus change relative to healthy
      controls (HCs). Data from 168 HC and 299 MCI participants were analyzed to
      determine sample sizes required to detect 25% slowing in mean rate of decline
      using global function, cognitive function, and structural measures as outcome
      variables. Reductions in estimated sample sizes of 10% to 43% were observed using
      the genetic enrichment strategy; reductions of 43% to 60% were observed with the
      neuroimaging enrichment strategy. Sample sizes needed to detect slowing in rate
      of atrophy in MCI relative to HC were dramatically larger than those needed to
      detect absolute change in atrophy rates. Constraining enrollment to MCI subjects
      with predictive atrophy on a screening MRI scan could improve the efficiency of
      clinical trials. Failure to take into account normal age-related changes risks
      under-powering trials designed to test disease-modifying properties of potential
      treatments.

PMID- 20683185
TI  - Clinical characteristics of patients with frontotemporal dementia with and
      without lobar atrophy on MRI.
AB  - INTRODUCTION: The presence of frontal and/or temporal atrophy on neuroimaging has
      been designated as supportive in the clinical consensus criteria for behavioral
      variant frontotemporal dementia (bvFTD). As magnetic resonance imaging (MRI) has
      a relatively low sensitivity for bvFTD, a substantial proportion of patients may
      present with a normal MRI. Thus, there may be clinical differences between
      patients with and without lobar abnormalities on MRI. We compared clinical
      characteristics of bvFTD patients with frontotemporal lobar atrophy on MRI to
      those lacking the typical pattern at presentation. METHODS: MRIs of 49 patients
      from our memory clinic, diagnosed with bvFTD were rated for the presence or
      absence of frontal and/or temporal atrophy. Demographic, behavioral, and
      cognitive features were compared between subjects with and without typical bvFTD
      atrophy pattern. RESULTS: Twenty-three patients showed lobar atrophy on MRI,
      whereas 26 patients lacked the characteristic frontotemporal lobar atrophy,
      including 13 patients with a normal MRI and 13 with other abnormalities.
      Disinhibition occurred more often in the group with frontal and/or temporal
      atrophy on MRI compared with the group with other abnormalities, whereas
      imitation did not occur in patients lacking the typical bvFTD atrophy pattern. No
      differences were found in neuropsychologic profiles. There was a trend for a
      lower mean Clinical Dementia Rating and less severe language impairment in
      patients with a normal MRI compared with the group with frontal and/or temporal
      atrophy. CONCLUSIONS: The clinical phenotype of FTD cannot be predicted by the
      presence or absence of lobar atrophy on MRI, although imitation and disinhibition
      are more prevalent in bvFTD patients with characteristic MRI abnormalities.
      Furthermore, patients with a normal MRI seem to be less severely demented in
      comparison to patients with frontal and/or temporal atrophy.

PMID- 20683186
TI  - Free and cued selective reminding identifies very mild dementia in primary care.
AB  - The Free and Cued Selective Reminding Test (FCSRT) is used widely to identify
      very mild dementia; 3 alternative scoring procedures have been proposed based on
      free recall, total recall, and cue efficiency. We compared the predictive
      validity of these scoring procedures for the identification of very mild
      prevalent dementia (CDR=0.5), of incident dementia, and for distinguishing
      Alzheimer Disease (AD) and nonAD dementias. We tested 244 elderly African
      American and White primary care patients at 18 month intervals using a screening
      neuropsychologic battery that included the FCSRT and a comprehensive diagnostic
      neuropsychologic battery. Median follow-up was 2.6 years. Dementia diagnoses were
      assigned using standard criteria without access to the results of the screening
      battery. There were 50 prevalent and 28 incident dementia cases. At scores
      selected to provide specificities of 90%, free recall was more sensitive to
      incident and prevalent dementia than the other 2 measures. Patients with impaired
      free recall were 15 times more likely to have a prevalent dementia and their risk
      of future dementia was 4 times higher than patients with intact free recall.
      Neither race nor education affected prediction although older patients were at
      increased risk of future dementia. Total recall was more impaired in AD dementia
      than in nonAD dementias. The results indicate that using the FCSRT, free recall
      is the best measure for detecting prevalent dementia and predicting future
      dementia. Total recall impairment supports the diagnosis of AD rather than nonAD
      dementia.

PMID- 20683187
TI  - Dementia mimicking Alzheimer's disease Owing to a tau mutation: CSF and PET
      findings.
AB  - The objective of the study was to illustrate the utility of positron emission
      tomography (PET) imaging using [C]PIB and [F]FDDNP together with cerebrospinal
      fluid (CSF) measures of amyloid-beta1 to 42 (Abeta42), total tau (t-tau) and tau
      phosphorylated at threonine 181 (p-tau) in the in vivo diagnosis of specific
      dementia syndromes. Two siblings fulfilling diagnostic criteria for familial
      Alzheimer's disease (AD) were investigated using [C]PIB and [F]FDDNP PET in
      combination with CSF measures of Abeta42, t-tau and p-tau. PET data were compared
      with paired [C]PIB and [F]FDDNP data from age-matched sporadic AD patients (n=9)
      and healthy controls (n=6). [C]PIB retention and CSF levels of Abeta42 in both
      patients resembled those of controls suggesting the presence of nonamyloid
      pathology. Genetic testing confirmed the absence of mutations in the presenilin 1
      gene in 1 patient; subsequent testing revealed the R406W tau mutation in both
      individuals leading to a diagnosis of frontotemporal dementia [F]FDDNP retention
      broadly correlated with CSF levels of t-tau and p-tau. Despite both individuals
      harbouring the same mutation, [F]FDDNP retention and CSF t-tau and p-tau were
      elevated in 1 patient, but not in the other. [C]PIB imaging and CSF measures of
      Abeta42 are useful in refuting the presence of underlying amyloid pathology.
      This, in combination with elevated levels of CSF t-tau and p-tau, has potential
      value in differential diagnosis of frontotemporal dementia from AD.

PMID- 20683189
TI  - Hearing history influences voice gender perceptual performance in cochlear
      implant users.
AB  - OBJECTIVES: The study was carried out to assess the role that five hearing
      history variables (chronological age, age at onset of deafness, age of first
      cochlear implant [CI] activation, duration of CI use, and duration of known
      deafness) play in the ability of CI users to identify speaker gender. DESIGN:
      Forty-one juvenile CI users participated in two voice gender identification
      tasks. In a fixed, single-interval task, subjects listened to a single speech
      item from one of 20 adult male or 20 adult female speakers and had to identify
      speaker gender. In an adaptive speech-based voice gender discrimination task with
      the fundamental frequency difference between the voices as the adaptive
      parameter, subjects listened to a pair of speech items presented in sequential
      order, one of which was always spoken by an adult female and the other by an
      adult male. Subjects had to identify the speech item spoken by the female voice.
      Correlation and regression analyses between perceptual scores in the two tasks
      and the hearing history variables were performed. RESULTS: Subjects fell into
      three performance groups: (1) those who could distinguish voice gender in both
      tasks, (2) those who could distinguish voice gender in the adaptive but not the
      fixed task, and (3) those who could not distinguish voice gender in either task.
      Gender identification performance for single voices in the fixed task was
      significantly and negatively related to the duration of deafness before cochlear
      implantation (shorter deafness yielded better performance), whereas performance
      in the adaptive task was weakly but significantly related to age at first
      activation of the CI device, with earlier activations yielding better scores.
      CONCLUSIONS: The existence of a group of subjects able to perform adaptive
      discrimination but unable to identify the gender of singly presented voices
      demonstrates the potential dissociability of the skills required for these two
      tasks, suggesting that duration of deafness and age of cochlear implantation
      could have dissociable effects on the development of different skills required by
      CI users to identify speaker gender.

PMID- 20683190
TI  - Americans hear as well or better today compared with 40 years ago: hearing
      threshold levels in the unscreened adult population of the United States, 1959
      1962 and 1999-2004.
AB  - OBJECTIVES: (1) To present hearing threshold data from a recent nationally
      representative survey in the United States (National Health and Nutrition
      Examination Survey, 1999-2004) in a distributional format that might be
      appropriate to replace Annex B in international (ISO-1999) and national (ANSI
      S3.44) standards and (2) to compare these recent data with older survey data
      (National Health Examination Survey I, 1959-1962) on which the current Annex B is
      based. DESIGN: Better-ear threshold distributions (selected percentiles and their
      confidence intervals) were estimated using linear interpolation. The 95%
      confidence intervals for the medians for the two surveys were compared
      graphically for each of the four age groups and for both men and women. In
      addition, we calculated odds ratios comparing the prevalences of better-ear
      hearing impairment (thresholds > 25 dB HL) between the two surveys, for 500,
      1000, 2000, and 4000 Hz, and for their four-frequency average. RESULTS: Across
      age and sex groups, median thresholds were lower (better) in the 1999-2004 survey
      at 500, 3000, 4000, and 6000 Hz (8000 Hz was not tested in the 1959-1962 survey).
      For both men and women, the prevalence of hearing impairment was significantly
      lower in 1999-2004 at 500, 2000, and 4000 Hz, but not at 1000 Hz. CONCLUSIONS:
      For men and women of a specific age, high-frequency hearing thresholds were lower
      (better) in 1999-2004 than in 1959-1962. The prevalences of hearing impairment
      were also lower in the recent survey. Differences seen at 500 Hz may be
      attributable at least in part to changes in standards for ambient noise in
      audiometry. The National Health and Nutrition Examination Survey 1999-2004
      distributions are offered as a possible replacement for Annex B in ISO-1999 and
      ANSI S3.44.

PMID- 20683191
TI  - Different expression of Sox9 and Runx2 between chondrosarcoma and
      dedifferentiated chondrosarcoma cell line.
AB  - Dedifferentiated chondrosarcoma (DDCS), a highly malignant variant of
      chondrosarcoma (CCS), is characterized by high-grade sarcoma adjacent to low
      grade chondroid tumor. Owing to its complicated composition, the histogenesis of
      this tumor remains controversial. Earlier, we carried out DNA microarray analysis
      using chondrosarcomatous tissues, and found that Sox9 and runt-related
      transcription factor 2 (Runx2) were differentially expressed in CCS compared with
      DDCS. Here, we analyzed Sox9, Runx2, Col2a1, and Col1a1 in NDCS-1 (DDCS) and
      SW1353 (CCS) cell lines using reverse transcriptase-polymerase chain reaction,
      western blot, and immunocytochemistry. The results showed high expression of
      Runx2 and Col1a1, and low expression of Sox9 and Col2a1 in NDCS-1 cells. In
      SW1353 cells, however, gene expressions were reversed. These findings provide
      evidence that Sox9 and Runx2 are involved in the occurrence and development of
      DDCS.

PMID- 20683192
TI  - Conservative and operative management of benign solid hepatic tumours: a
      successful stratified algorithm.
AB  - BACKGROUND: The progress of modern imaging studies has improved the diagnostic
      approach of benign liver tumours, leading to a tailored approach with increased
      conservative management. METHODS: One hundred and thirty-two patients suffering
      from benign hepatic tumours were enrolled in this study, including an operative
      (group I, 49 patients) and a conservative (group II, 83 patients) management.
      Patients' tumour and treatment features were analyzed. RESULTS: The mean
      patients' age was 39 years. Indication for resection based on diagnosis of tumour
      nature (hepatic cell adenoma or uncertain diagnosis) and significant tumour
      related abdominal pain was 15% out of 33 patients with hepatic haemangioma, 21.7%
      out of 60 patients with focal nodular hyperplasia and 78.4% out of 37 patients
      with hepatocellular adenoma. Mortality was nihil in group I. Complications and
      transfusion rates were related to the performance of major hepatectomy, when
      required for huge tumours. With a 95.5% of complete patients' follow-up during a
      mean of 92 months in group I and 87 months in group II, no misdiagnosis or
      evolution towards malignancy was encountered. Interestingly, 87.9% of all
      observed benign liver tumours remained stable, decreased in size or disappeared.
      None of the remaining lesions required surgery. CONCLUSION: A restrictive policy
      of surgical management of benign liver tumours based on clinical symptoms, tumour
      size and nature on imaging studies (including dubious lesions) and tumour
      biopsies in selected cases is safe and reliable with a low-operative mortality in
      resected patients and satisfactory disease-control in the vast majority of
      observed benign liver tumours.

PMID- 20683193
TI  - Breastfeeding and the risk of malaria in children born to HIV-infected and
      uninfected mothers in rural Uganda.
AB  - BACKGROUND: Early cessation of breastfeeding increases morbidity and mortality of
      children born to HIV-infected mothers in resource-limited settings. However, data
      on whether breastfeeding reduces the risk of malaria in HIV-exposed and HIV
      infected children is limited. METHODS: We prospectively followed 99 HIV-unexposed
      children, 202 HIV-exposed children, and 45 HIV-infected children in a high
      malaria transmission area in Uganda. All children were given insecticide-treated
      bednets. HIV-exposed and HIV-infected children were given trimethoprim
      sulfamethoxazole prophylaxis. Malaria diagnosis was based on fever and a positive
      blood smear. Date of breastfeeding cessation was determined through monthly
      questionnaires. Associations between breastfeeding and the risk of malaria were
      modeled through binomial generalized estimating equations using multivariate
      analysis adjusting for repeated measures, age, and location of residence.
      Analyses were stratified according to mothers' and children's HIV status.
      RESULTS: Breastfeeding was associated with a significantly lower risk of malaria
      in 6-15 months old HIV-exposed children (relative risk [RR] = 0.62; P = 0.008)
      and 6-15 months old HIV-infected children (RR = 0.31; P = 0.002). However,
      breastfeeding was not protective against malaria for >15-24 months old HIV
      unexposed (RR = 1.14; P = 0.21) or >15-24 months old HIV-infected children (RR =
      1.11; P = 0.75). CONCLUSIONS: HIV-infected mothers should be counseled about the
      importance of breastfeeding and trimethoprim-sulfamethoxazole prophylaxis to
      protect their young children and themselves against malaria.

PMID- 20683194
TI  - Long-term outcomes of a national expanded access program to antiretroviral
      therapy: the Chilean AIDS cohort.
AB  - OBJECTIVE: To evaluate impact of the program after up to 6 years of follow-up in
      survival, virologic, and immunologic response. METHODS: Prospective follow-up of
      patients initiating first highly active antiretroviral therapy from 2001 to 2007.
      Chile began in 2001 an expanded access program to antiretroviral therapy. The
      Chilean AIDS Cohort has enrolled >85% of patients from this program in the public
      health system. STATISTICAL ANALYSIS: chi2, Fisher tests, survival, univariate and
      multivariate analysis. RESULTS: Five thousand one hundred fifteen adults (16%
      women); median follow-up: 3.64 years (18,159 patient-years). At baseline: median
      age, 35.8 years; 45.6% had clinical AIDS; median CD4 cell count, 102 cells per
      cubic millimeter. Global mortality, 9.0%; loss to follow-up, 6.8%. Probability of
      survival at 1 and 5 years were 0.95 and 0.89, respectively. First regimen was
      maintained in 72% of those alive and in control at 1 year and 48% at end of
      study. Main reason for therapy change/discontinuation was drug toxicity (44.9%).
      At last visit, 74% of active patients had viral suppression, and median CD4 cell
      count had reached 301 cells per cubic millimeter. CONCLUSIONS: In this middle
      income country, wide access highly active antiretroviral therapy has been
      successfully implemented and evaluated. Despite advanced disease at initiation,
      survival, clinical, virologic, and immunologic outcomes have been comparable with
      that of industrialized countries.

PMID- 20683195
TI  - The role of transplacental microtransfusions of maternal lymphocytes in in utero
      HIV transmission.
AB  - BACKGROUND: The mechanisms of HIV transmission from mothers to infants are poorly
      understood. A possible mechanism of in utero transmission is transplacental
      transfer of HIV-infected maternal leukocytes into the fetal circulation during
      pregnancy. OBJECTIVE: To determine if the frequency of in utero HIV infection
      correlates with presence or levels of maternal cells (MCs) in placenta-derived
      cord blood. METHODS: DNA was extracted from dried cord blood spots (DBS) from
      newborns born to HIV+ mothers and corresponding maternal DBS specimens. Paired
      mother-infant samples were probed to identify unique maternal sequences targeted
      by 24 allele-specific real-time polymerase chain reaction assays. Infant DBS
      derived DNA was then probed in replicate analyses for noninherited maternal
      allelic sequences. Rates of detection and levels of MCs in DBS samples of HIV(+)
      and HIV(-) newborns were compared. RESULTS: Of 114 mother-infant pairs with
      informative alleles, 38 newborns were HIV(+) and 76 HIV(-), based on detection of
      HIV DNA/RNA at birth. MC were detected in 23 of 38 HIV(+) newborns (60.5%) and in
      47 of 76 HIV(-) newborns (61.8%). The mean and median concentrations of nucleated
      MCs in DBS for the HIV(+)/MC(+) newborns (n = 23) were 0.33% and 0.27%,
      respectively, compared with 0.09% and 0.10% for the HIV(-)/MC(+) newborns (n =
      47) (2-sample T test for means: P = 0.78). CONCLUSIONS: There was no significant
      difference in rates of detection or concentrations of MC in DBS between HIV(+)
      and HIV(-) newborns. Therefore, we could not demonstrate a correlation between MC
      in DBS, assumed to reflect levels of in utero maternal-fetal cell trafficking,
      and the risk of in utero HIV transmission.

PMID- 20683196
TI  - Paraneoplastic pemphigus in a burn intensive care unit: case report and review of
      the literature.
AB  - Paraneoplastic pemphigus is a rare cause of acute diffuse blistering in the adult
      patient. It commonly presents with subepidermal blistering, epidermal necrosis,
      and symptoms of mucosal irritation, such as conjunctivitis and vaginal
      ulceration. Because of its rarity, it is frequently misdiagnosed as Stevens
      Johnson syndrome or toxic epidermal necrolysis. In this study, the authors will
      describe clinical and histologic manifestations of paraneoplastic pemphigus. This
      case report describes a 45-year-old woman with paraneoplastic pemphigus who was
      admitted and treated in a burn intensive care unit. Although initially diagnosed
      with Stevens-Johnson syndrome, the patient had progression of desquamation when
      potentially offending medications were discontinued. Diffuse adenopathy was noted
      on examination, and biopsy confirmed a low-grade lymphoma. Paraneoplastic
      pemphigus is a rare but important cause of acute diffuse blistering in adults.
      This disorder should be considered in the differential diagnosis of patients with
      diffuse blistering.

PMID- 20683197
TI  - Predicting functional outcome for children on admission after burn injury: do
      parents hold the key?
AB  - In this study, a predictive model about recovery postburn was developed for
      purposive case selection using explanatory case methodology. Seven cases (each
      comprising a child, caregiver, and teacher) participated. Children were aged 6 to
      13 years with between 2% and 35% TBSA burned. Caregivers completed assessments of
      premorbid family and child-adaptive functioning, and family, parental, and child
      functioning during acute and postacute treatment periods. Teachers completed
      assessment of premorbid and postacute child-adaptive functioning. Children and
      their respective caregivers were interviewed to obtain further insights into
      outcomes. Assessments and interviews were completed before skin healing, on skin
      healing, and at 6 months postburn injury. Descriptive analysis of the
      quantitative data and content analysis of qualitative data was undertaken for
      individual cases and across all cases. In keeping with the explanatory case
      methodology, replication logic was applied to each case to determine the extent
      to which theoretical propositions based on the predictive model were supported.
      Findings suggest that children whose parents had high state anxiety in
      combination with ineffective coping strategies seemed most at risk of a
      nonadaptive outcome after a burn injury. There was little support for the rival
      explanations that child and family functioning or injury severity most
      consistently predicted outcome postburn injury.

PMID- 20683198
TI  - Nighttime noise issues that interrupt sleep after cardiac surgery.
AB  - Patients' perceptions of noise events that prevent/interrupt nighttime sleep
      after cardiac surgery and sleep promotion aids were studied for associations with
      patient characteristics. Overhead paging, equipment, and loud communication
      prevented/interrupted nighttime sleep; however, most patient characteristics were
      not associated with the presence or absence of these noise events. Patients
      selected pain medication to promote sleep. Other sleep aids were used
      infrequently. Behavioral and structural noise reduction interventions are needed
      to minimize sleep interruptions.

PMID- 20683199
TI  - Image of the month. Gone fishin': a surprising finding while investigating
      possible eosinophilic esophagitis.

PMID- 20683200
TI  - Bowel preparation for pediatric colonoscopy procedures.
AB  - Colonoscopy is a routinely performed procedure in children and adolescents.
      Proper visualization of the intestinal mucosa, completion of the procedure,
      including examination of the terminal ileum, detection of pathological lesions,
      and therapeutic maneuvers, all are highly dependent on the quality of the bowel
      preparation. A significant proportion of patients, in some reports up to one
      third, are inadequately prepared for the examination, which leads to extended
      procedure time, incomplete examination, or need for repeat procedure. Aside from
      efficacy and safety, the most important aspects of colon preparation in
      pediatrics are ease of administration, palatability, dietary restriction, and
      minimization of disruption of daily routine. An ideal preparation does not exist
      and a wide variety of regimens are being used. Several of these have been
      investigated in pediatric clinical trials. This article reviews the published
      literature with an emphasis on the most commonly used agents, their mechanism of
      action, efficacy and ease of use, and safety.

PMID- 20683201
TI  - Analysis of gene mutations in children with cholestasis of undefined etiology.
AB  - BACKGROUND: The discovery of genetic mutations in children with inherited
      syndromes of intrahepatic cholestasis allows for diagnostic specificity despite
      similar clinical phenotypes. Here, we aimed to determine whether mutation
      screening of target genes could assign a molecular diagnosis in children with
      idiopathic cholestasis. PATIENTS AND METHODS: DNA samples were obtained from 51
      subjects with cholestasis of undefined etiology and surveyed for mutations in the
      genes SERPINA1, JAG1, ATP8B1, ABCB11, and ABCB4 by a high-throughput gene chip.
      Then, the sequence readouts for all 5 genes were analyzed for mutations and
      correlated with clinical phenotypes. Healthy subjects served as controls.
      RESULTS: Sequence analysis of the genes identified 14 (or 27%) subjects with
      missense, nonsense, deletion, and splice site variants associated with disease
      phenotypes based on the type of mutation and/or biallelic involvement in the
      JAG1, ATP8B1, ABCB11, or ABCB4 genes. These patients had no syndromic features
      and could not be differentiated by biochemical markers or histopathology. Among
      the remaining subjects, 10 (or ~20%) had sequence variants in ATP8B1 or ABCB11
      that involved only 1 allele, 8 had variants not likely to be associated with
      disease phenotypes, and 19 had no variants that changed amino acid composition.
      CONCLUSIONS: Gene sequence analysis assigned a molecular diagnosis in 27% of
      subjects with idiopathic cholestasis based on the presence of variants likely to
      cause disease phenotypes.

PMID- 20683202
TI  - Follow-up in children with progressive familial intrahepatic cholestasis after
      partial external biliary diversion.
AB  - OBJECTIVES: The aim of this study was to examine whether reversion of
      histological fibrosis followed partial external biliary diversion (PEBD) in
      patients with progressive familial intrahepatic cholestasis (PFIC); whether the
      duration of cholestatic episodes after PEBD influenced the evolution of fibrosis;
      and whether genotyping was helpful in predicting outcome of PEBD. PATIENTS AND
      METHODS: Children with PFIC who underwent PEBD were investigated with genetic,
      biochemical, and anthropometric standard methods. Serial liver specimens were
      assessed histologically without knowledge of genotype and outcome. Findings were
      evaluated in the contexts of the total duration of cholestasis and the clinical
      outcome after PEBD. RESULTS: From a total of 18 children with PFIC, 13 underwent
      PEBD, and 12 of these (among them 10 with identified ABCB11 mutations) were
      amenable for clinical and histological follow-up. When compared with baseline at
      PEBD, statistically significant reductions were found in histological cholestasis
      1 and 3 years after PEBD, and in fibrosis 5 and >10 years after PEBD. The
      relative duration of cholestatic episodes after PEBD was positively correlated
      with the severity of fibrosis. Children homozygous for the missense mutation
      c.890A>G in ABCB11 responded well to PEBD. CONCLUSIONS: Biliary diversion should
      be regarded as the first choice of surgical treatment in noncirrhotic patients
      with severe ABCB11 disease and may also be efficacious in other forms of PFIC.

PMID- 20683203
TI  - Comparative effects of probiotics, prebiotics, and synbiotics on growth factors
      in the large bowel in a rat model of formula-induced bowel inflammation.
AB  - OBJECTIVES: Supplementation with probiotics has been shown to prevent
      gastrointestinal damage possibly through preservation of growth factors. We
      tested the hypothesis that probiotics, prebiotics, or synbiotics supplementation
      preserves intestinal insulin-like growth factors (IGFs) and epidermal growth
      factors (EGFs) in formula-fed neonatal rats. MATERIALS AND METHODS: At birth
      (postnatal day 0 [P0]), neonatal rat pups (n = 18 pups/group) were either
      maternally fed or hand-gavaged with formula supplemented with probiotics (Pro
      Fed), prebiotics, or synbiotics from P0 to P3. A formula-fed control group
      received formula without supplementation. At P4, large bowel samples were
      assessed histologically and assayed for vascular endothelial growth factor
      (VEGF), soluble VEGF receptor-1, IGF-I, IGF-II, and EGF. RESULTS: All formula-fed
      groups were severely growth suppressed with comparable mortalities. Moderate
      preservation of bowel integrity was noted in the Pro-Fed group. In contrast,
      severe inflammation was seen in all of the other formula groups. This was
      associated with significant increases in VEGF levels in all of the formula groups
      (P < 0.05) except the Pre-Fed group. Similar elevations in soluble VEGF receptor
      1 (P < 0.05), IGF-I (P < 0.05), and EGF (P < 0.05) were noted, but statistical
      significance was achieved only in the Pro-Fed group. CONCLUSIONS: Induction of
      IGF-I and EGF with moderate bowel integrity may represent a protective effect of
      probiotics against formula-induced inflammation. These data, taken collectively,
      suggest that probiotics may provide more beneficial effects on the developing
      large bowel than prebiotics and synbiotics.

PMID- 20683204
TI  - Alterations of the intestinal barrier in patients with autism spectrum disorders
      and in their first-degree relatives.
AB  - OBJECTIVES: Intestinal permeability (IPT) was investigated in patients with
      autism as well as in their first-degree relatives to investigate leaky gut
      hypothesis. Faecal calprotectin (FC) was also measured in patients with autism,
      either with or without gastrointestinal symptoms, and in their first-degree
      relatives. PATIENTS AND METHODS: IPT results, assessed by means of the
      lactulose/mannitol test, were compared with adult and child controls and with FC
      values. RESULTS: A high percentage of abnormal IPT values were found among
      patients with autism (36.7%) and their relatives (21.2%) compared with normal
      subjects (4.8%). Patients with autism on a reported gluten-casein-free diet had
      significantly lower IPT values compared with those who were on an unrestricted
      diet and controls. Gastrointestinal symptoms were present in 46.7% of children
      with autism: constipation (45.5%), diarrhoea (34.1%), and others (alternating
      diarrhoea/constipation, abdominal pain, etc: 15.9%). FC was elevated in 24.4% of
      patients with autism and in 11.6% of their relatives; it was not, however,
      correlated with abnormal IPT values. CONCLUSIONS: The results obtained support
      the leaky gut hypothesis and indicate that measuring IPT could help to identify a
      subgroup of patients with autism who could benefit from a gluten-free diet. The
      IPT alterations found in first-degree relatives suggest the presence of an
      intestinal (tight-junction linked) hereditary factor in the families of subjects
      with autism.

PMID- 20683205
TI  - Overlap, common features, and essential differences in pediatric granulomatous
      inflammatory bowel disease.
AB  - Overlap in the clinical presentation of pediatric granulomatous inflammatory
      bowel disease may be substantial, depending on the mode of presentation. Chronic
      granulomatous disease (CGD) may present with granulomatous colitis, perianal
      abscesses, hepatic abscesses or granulomas, failure to thrive, and obstruction of
      the gastrointestinal tract (including esophageal strictures and dysmotility,
      delayed gastric emptying, and small bowel obstruction). Anemia, thrombocytosis,
      elevated C-reactive protein and erythrocyte sedimentation rate, and
      hypoalbuminemia are nonspecific and may occur in any of the granulomatous
      inflammatory bowel diseases. In histology, macrophages with cytoplasmic
      inclusions will be rather specific for CGD. Sarcoidosis may present with
      abdominal pain or discomfort, diarrhea, weight loss, growth failure, delayed
      puberty, erythema nodosum, arthritis, uveitis, and hepatic granulomata. Only in
      55% of the patients will angiotensin-converting enzyme be elevated. The
      noncaseating epithelioid granulomata will be unspecific. Bronchoalveolar
      lymphocytosis and abnormalities in pulmonary function are reported in sarcoidosis
      and in Crohn disease (CD) and CGD. Importantly, patients with CD may present with
      granulomatous lung disease, fibrosing alveolitis, and drug-induced pneumonitis.
      Sarcoidosis and concomitant gastrointestinal CD have been reported in patients,
      as well as coexistence of CD and sarcoidosis in siblings. Common susceptibility
      loci have been identified in CD and sarcoidosis. CD and CGD share defects in the
      defense mechanisms against different microbes. In the present review, common
      features and essential differences are discussed in clinical presentation and
      diagnostics--including histology--in CGD, sarcoidosis, and CD, together with 2
      other granulomatous inflammatory bowel diseases, namely abdominal tuberculosis
      and Hermansky-Pudlak syndrome. Instructions for specific diagnosis and respective
      treatments are provided.

PMID- 20683206
TI  - Role of endoscopic ultrasound for evaluating gastrointestinal tract disorders in
      pediatrics: a tertiary care center experience.
AB  - BACKGROUND: Endoscopic ultrasound (EUS) with or without fine needle aspiration
      (FNA) has a well-established role in the evaluation of various gastrointestinal
      (GI) tract disorders in adults. The clinical impact of EUS on the management of
      the pediatric population remains less clear. This study evaluates the
      feasibility, safety, and applications of EUS +/- FNA in pediatric GI tract
      disorders. PATIENTS AND METHODS: Using a prospectively maintained EUS database,
      all patients 18 years of age or younger referred for EUS at our institution were
      identified. Retrospective chart review was conducted to document procedure
      indications, type of anesthesia used, EUS findings, final FNA cytology results,
      and clinical impact of EUS +/- FNA on the subsequent management of pediatric
      patients. RESULTS: Fifty-eight EUS procedures were performed in 56 patients (35
      girls). Median age was 16 years (range 4-18 years). The main indications for EUS
      were acute or recurrent pancreatitis, abdominal pain of suspected
      pancreatobiliary origin, suspected biliary obstruction, upper GI
      mucosal/submucosal lesions, and evaluation of pancreatic abnormalities seen on
      prior imaging. Sedation used included nurse-administered propofol sedation in 38
      (73%), general anesthesia in 9 (17%), and fentanyl with meperidine in 3 (6%).
      Five therapeutic procedures performed included celiac plexus blocks in 4 and 1
      EUS-guided pancreatogram. In 44 (86%) patients, EUS provided a new diagnosis. The
      procedure was successfully completed in all patients with no reported
      complications. CONCLUSIONS: EUS +/- FNA is feasible and safe and makes a
      significant impact on most pediatric patients. Nurse-administered propofol
      sedation appears to be safe and well tolerated in this group.

PMID- 20683207
TI  - Slow hematological recovery in children with IBD-associated anemia in cases of
      "expectant management".
AB  - BACKGROUND AND OBJECTIVE: Allowing children with inflammatory bowel disease (IBD)
      to live with subnormal hemoglobin (Hb) levels affects their quality of life. The
      therapeutic approach to normalize Hb varies according to the cause of IBD
      associated anemia. In exclusive iron-deficiency anemia (IDA) repletion of iron
      stores is obligatory, whereas controlling inflammation is the treatment of choice
      for anemia of chronic disease (ACD). In daily practice the focus is on control of
      intestinal inflammation, and spontaneous hematological recovery is awaited. The
      aim of the present study was to evaluate the hematological effect of "expectant
      management" on newly diagnosed pediatric patients with IBD with anemia. PATIENTS
      AND METHODS: Medical records of children with IBD were reviewed. Study endpoints
      were the difference in Hb from the moment of IBD diagnosis (T0) to the end of the
      induction phase (T1), and time until normalization of Hb, stratified for the type
      of anemia at T0. RESULTS: A total of 103 children were included in the study, of
      whom 80 (78%) had anemia at T0. Exclusive IDA was found in 58% of them. Expectant
      management caused a modest increase in Hb between T0 and T1 for both types of
      anemia (IDA 0.4 mmol/L; ACD 0.5 mmol/L), but 65 of 80 children (81%) still had
      anemia at T1. The proportion of children with exclusive IDA had increased to 74%.
      One third of the cases initially classified as having ACD had progressed to
      exclusive IDA. There was no significant difference in time until normalization of
      Hb between children with exclusive IDA and ACD. Twelve months after IBD diagnosis
      24% of the group initially diagnosed as having exclusive IDA and 50% of the ACD
      group were still anemic. CONCLUSIONS: Hematological recovery in children with IBD
      associated anemia is slow with expectant management, regardless of the type of
      anemia at T0. Present results underline the need for a more active approach to
      improve Hb.

PMID- 20683208
TI  - Anti-vascular endothelial growth factor treatment in combination with
      chemotherapy delays hematopoietic recovery due to decreased proliferation of bone
      marrow hematopoietic progenitor cells.
AB  - INTRODUCTION: Targeting of cancer by chemotherapy in combination with anti
      vascular endothelial growth factor (VEGF) therapy has demonstrated not only the
      clinical efficacy but also a higher risk of serious hematologic complications
      including neutropenia. The purpose of the study was to elucidate the molecular
      mechanisms responsible for the development of neutropenia during the combination
      treatment. METHODS: Mouse model and in vitro studies were undertaken to determine
      the effect of interference with VEGF signaling by VEGF-specific agents or a
      multitargeted VEGF receptor (VEGFR) tyrosine kinase inhibitor on proliferation of
      hematopoietic progenitor cell (HPC) and repopulation of the hematopoietic
      compartment after myeloablation. RESULTS: The studies demonstrated that blockage
      of VEGFR1 or VEGFR2 signaling decreased HPC proliferation and impaired
      repopulation of the hematopoietic compartment after myelosuppression by slowing
      the progression of HPC through the cell cycle. The combination of cytotoxic drugs
      and VEGFR tyrosine kinase inhibitor had an additive inhibitory effect and
      decreased proliferation of HPC significantly stronger than either agent alone.
      CONCLUSIONS: Signaling through both VEGFR1 and VEGFR2 is required for normal
      reconstitution of the hematopoietic compartment after cytotoxic chemotherapy.

PMID- 20683209
TI  - Japanese Lung Cancer Registry Study: first prospective enrollment of a large
      number of surgical and nonsurgical cases in 2002.
AB  - PURPOSE: To investigate prognoses of lung cancer patients prospectively enrolled
      in the Japan Lung Cancer Registry Study. METHODS: Patients newly diagnosed as
      having lung cancer exclusively in 2002 were enrolled. Follow-up surveys were
      performed twice, in 2004 and 2009, and the final follow-up data with prognoses
      were analyzed for 14,695 patients (79%). Clinical stages were defined according
      to the sixth edition of the International Union Against Cancer--tumor, node,
      metastasis classification (2002). RESULTS: The mean age was 67.1 years (range, 18
      89 years), and there were 10,194 men (69.3%) and 4315 women (29.7%). The most
      frequent histology was adenocarcinoma (n = 8325, 56.7%), followed by squamous
      cell carcinoma (n = 3778, 26%) and small cell carcinoma (n = 1345, 9.2%). The
      distribution of clinical stages was as follows: IA, 4245 cases (29.3%); IB, 2248
      (14.5%); IIA, 208 (1.4%); IIB, 918 (6.3%); IIIA, 1700 (11.8%); IIIB, 2110
      (16.3%); and IV, 3037 (21.0%). The 5-year survival rates were 44.3% for all
      patients, 46.8% for those with non-small cell lung cancer, and 14.7% for those
      with small cell lung cancer. According to the clinical stage of non-small cell
      lung cancer and small cell lung cancer, the 5-year survival rates were 79.4 and
      52.7% for stage IA, 56.9 and 39.3% for IB, 49.0 and 31.7% for IIA, 42.3 and 29.9%
      for IIB, 30.9 and 17.2% for IIIA, 16.7 and 12.4% for IIIB, and 5.8 and 3.8% for
      IV, respectively. CONCLUSION: Analysis of a large cohort in the Japanese registry
      study found that stage-specific prognosis was within a range similar to other
      reports. The data presented should provide an important reference for future
      clinical trials in Japan.

PMID- 20683210
TI  - Severe interstitial lung disease associated with amrubicin treatment.
AB  - BACKGROUND: Amrubicin is a novel anthracycline agent that is well known to exert
      significant activity against small cell lung cancer (SCLC), but the adverse
      pulmonary effects of amrubicin are less well known. We investigated the incidence
      of acute interstitial lung disease (ILD) in SCLC patients who had been treated
      with amrubicin. METHODS: Medical records were used to retrospectively investigate
      a total of 100 cases of SCLC patients treated with single-agent amrubicin therapy
      at the National Cancer Center Hospital East between June 2003 and March 2008. The
      patients' radiographic records and clinical data were reviewed to identify
      patients who had developed acute ILD after being treated with amrubicin. RESULTS:
      After receiving amrubicin, seven of the 100 SCLC patients subsequently developed
      pulmonary infiltrates, and they were identified as cases of acute ILD associated
      with amrubicin. Of the seven patients who developed ILD, six were treated with
      corticosteroids, and the ILD improved in three of them, but the other three
      patients died of respiratory failure. The incidence of ILD was 33% (4/12) among
      the patients with pre-existing pulmonary fibrosis (PF) and 3% (3/88) among the
      patients without PF, and the difference between the two groups was statistically
      significant (P = 0.0036). CONCLUSIONS: The results of this study indicated that
      amrubicin may cause severe ILD and that pre-existing PF was associated with a
      higher rate of ILD among SCLC patients treated with amrubicin. We recommend not
      administering amrubicin in the treatment of SCLC patients with pre-existing PF.

PMID- 20683211
TI  - Wide distribution of the serum dehydroepiandrosterone and sex steroid levels in
      postmenopausal women: role of the ovary?
AB  - OBJECTIVE: Because the exclusive source of sex steroids (at least estrogens)
      after menopause is recognized to be dehydroepiandrosterone (DHEA), this study
      examines the interindividual variability of serum DHEA and its metabolites as
      well as the contribution of the ovary to global sex steroid physiology in
      postmenopausal women. METHODS: Serum levels of DHEA and 11 of its metabolites
      were measured by gas or liquid chromatography/mass spectrometry in 442 intact and
      71 ovariectomized postmenopausal women aged 42 to 74 years. RESULTS: With a mean
      +/- SD concentration of 2.03 +/- 1.33 ng/mL, serum DHEA in intact postmenopausal
      women is highly variable with 5th and 95th centiles at 0.55 and 4.34 ng/mL,
      respectively, for a 7.9-fold difference. A comparable variability is observed for
      the 11 metabolites of DHEA. The 22.3% higher serum DHEA in intact compared with
      ovariectomized women is accompanied by parallel differences for all the other
      steroids, thus indicating that all sex steroids originate from circulating DHEA
      in postmenopausal women with no direct secretion of active estrogens or androgens
      by the postmenopausal ovary. CONCLUSIONS: The 7.9-fold difference between low and
      high serum DHEA levels provides an explanation for the lack of signs of hormone
      deficiency in some women, whereas most of them have symptoms or signs. The
      approximately 20% contribution of the ovary to the total pool of DHEA with no
      direct secretion of estrogens or androgens in the circulation could possibly
      explain the reported negative effect of oophorectomy on longevity, especially
      from coronary heart disease events.

PMID- 20683212
TI  - Acyclovir or Abeta42 peptides attenuate HSV-1-induced miRNA-146a levels in human
      primary brain cells.
AB  - Human brains harbor herpes simplex virus type-1 (HSV-1) DNA, which normally
      remains quiescent throughout many decades of life. HSV-1 is associated with viral
      encephalopathy and with the amyloid beta 42 (Abeta42) peptide-enriched lesions
      that characterize Alzheimer's disease neuropathology. Here we report that
      infection of human neuronal-glial cells in primary co-culture with HSV-1 induces
      an irregular hypertrophy of human neuronal-glial cell bodies, an induction of HSV
      1 DNA polymerase, and an up-regulation of micro-RNA-146a associated with altered
      innate-immune responses. Presence of the antiviral acyclovir or soluble Abeta42
      peptide significantly attenuated these neuropathological responses. The
      inhibitory effects of Abeta42 peptide were also observed in an HSV-1-infected CV
      1 cell-based viral plaque assay. The results suggest that soluble Abeta42 peptide
      can invoke non-pathological and anti-viral effects through inactivation of an HSV
      1 challenge to human brain cells by simple viral sequestration, viral
      destruction, or by complex neurogenetic mechanisms.

PMID- 20683213
TI  - Endoscopic treatment of arachnoid cysts: a detailed account of surgical
      techniques and results.
AB  - BACKGROUND: Surgical treatment of arachnoid cysts remains under debate. Although
      many authors favor endoscopic techniques, others attribute a higher recurrence
      rate to the endoscope. OBJECTIVE: The authors report their experience with
      endoscopic procedures for arachnoid cyst. METHODS: All pure endoscopic procedures
      for arachnoid cysts performed by the authors were analyzed. Particular reference
      was given to surgical complications and patient outcome in relation to cyst
      location and endoscopic technique. RESULTS: Sixty-six endoscopic procedures were
      performed in 61 patients (mean age, 28 years; range, 23 days to 74 years; 35
      males, 26 females). The main presenting symptoms were cephalgia (61%),
      hemisymptoms (18%), and macrocephalus (18%). Cyst location was temporobasal
      (34%), suprasellar (21%), at the cisterna quadrigemina (18%), paraxial
      supratentorial (16%), and various (10%). Thirty cystocisternostomies, 14
      ventriculocystostomies, 12 cystoventriculostomies, and 10
      ventriculocystocisternostomies were performed. The overall clinical success rate
      was 90%. The endoscopic technique was abandoned in 4 cases (7%). Postoperative
      complications were found in 16%; there was only one permanent deficit (2%). Five
      recurrences (8%) occurred up to 7 years after the first procedure. Of the various
      locations, the temporobasal cysts were the most difficult to treat with lowest
      clinical success (81%), highest recurrence (19%), and highest complication rate
      (24%). Of the various endoscopic techniques, ventriculocystostomy and
      ventriculocystocisternostomy reached the highest success rates with 100%.
      CONCLUSIONS: Endoscopic techniques provide very good results in arachnoid cyst
      treatment. The most frequent cyst location is the most difficult to treat. A long
      term follow-up is recommended since recurrences can occur many years after the
      procedure.

PMID- 20683214
TI  - Clear cell meningiomas: three case reports with genetic characterization and
      review of the literature.
AB  - BACKGROUND AND IMPORTANCE: Intracranial clear cell meningioma is very rare. We
      present 3 cases of intracranial clear cell meningiomas genetically characterized
      by comparative genomic hybridization with a review of the literature. CLINICAL
      PRESENTATION: Patient 1 is a 38-year-old woman with a petroclival tumor. Patient
      2 is a 60-year-old man with a tumor at the foramen magnum. Patient 3 is a 60-year
      old man with a tumor at the posterior clinoid process. Gross total resection was
      performed in patients 1 and 2. Patient 1 has been free from recurrence for 10
      years. Patient 2 had a tumor recurrence at 14 months after the operation. After
      partial resection, conventional radiotherapy was given, and there was no tumor
      regrowth at 2 years after radiotherapy. Subtotal resection was performed in
      patient 3, and no regrowth was detected for 3 months. Histologically, all tumors
      were composed of cells with clear cytoplasm reactive for periodic acid-Schiff and
      diagnosed as clear cell meningioma. The MIB-1 and p53 staining indexes were 1.8,
      1.7, and 5.6 and 1.1, 1.0, and 5.5, respectively. Comparative genomic
      hybridization revealed no chromosomal number aberrations in patient 1, numerous
      losses and gains including loss of chromosome 1 in patient 2, and loss of only
      22q in patient 3. Because staining indexes of MIB-1 and p53 were equivalent in 2
      patient (patients 1 and 2) with a long follow-up period, the contrary clinical
      courses are likely associated with genetic characteristics. CONCLUSION: To the
      best of our knowledge, this is the first report that suggests association between
      tumor behavior and genetic characteristics in clear cell meningiomas.

PMID- 20683215
TI  - Primary pancreatic lymphoma: a clinical quandary of diagnosis and treatment.
AB  - OBJECTIVE: To investigate the clinical feature and treatment strategy of primary
      pancreatic lymphoma. METHODS: Thirty-nine cases of primary pancreatic lymphoma
      reported in China were reviewed retrospectively with their clinical characters,
      treatment, and outcome, as well as a literature review of worldwide reports.
      RESULTS: The major clinical presentations included discomfort or pain in the
      upper abdomen and jaundice without specificity. Only 2 cases were identified
      correctly by computed tomography, and 5 cases obtained a positive finding in a
      biopsy before operation. Thirty-two patients accepted operation; 13
      pancreatoduodenectomy and 6 distal pancreatectomy were performed. Thirty-one
      patients accepted postoperative chemotherapy. Until now, 26 patients are still
      alive at a range of 3 to 72 months; 5 patients died at 5 to 24 months after
      operation. Literature review revealed 85 additional cases of pancreatic lymphoma
      in English reports. Their diagnosis and treatment methods varied. CONCLUSIONS:
      Primary pancreatic lymphoma was misdiagnosed as pancreatic adenocarcinoma
      frequently. Fine needle aspiration biopsy is the most valuable method in
      preoperative diagnosis. The cyclophosphamide, doxorubicin, vincristine, and
      prednisone scheme was still the most commonly used regimen of chemotherapy. The
      value of surgery and radiotherapy remains controversial; an operation combining
      chemotherapy seems to be an appropriate method of treatment for a patient in whom
      malignancy cannot be ruled out.

PMID- 20683216
TI  - Multimodality treatment of pancreatic cancer with liver metastases using
      chemotherapy, radiation therapy, and/or Chinese herbal medicine.
AB  - OBJECTIVE: To explore the utility of multidisciplinary approaches in the
      treatment of patients with pancreatic cancer with liver metastases (PCLM).
      METHODS: From 2002 to 2007, a total of 164 consecutive patients with PCLM treated
      with chemotherapy, radiation therapy, and/or Chinese herbal medicine were
      included in this study. Clinical parameters, treatments received, and survival
      time from initial diagnosis were analyzed. RESULTS: Of the 164 patients, 113
      (69%) were men and 51 (31%) were women, with median age of 58 years. One hundred
      thirty-two patients (80%) had synchronous liver metastases, and 57 patients (35%)
      had extrahepatic metastases. Overall median survival time of the 164 patients was
      4.7 months; 23 (14%) were alive at least 12 months after initial diagnosis of
      liver metastases. Karnofsky performance status of less than 80, weight loss (>10%
      within 6 months), ascites, and carbohydrate antigen 19-9 of 1000 U/mL or greater
      were the most relevant predictors of poor survival. Multivariate analysis showed
      that chemotherapy and Chinese herbal medicine were protective factors.
      CONCLUSIONS: Multimodality treatment is well tolerated by patients with PCLM and
      may be effective in prolonging their survival. Awareness of the implications of
      these prognostic factors may assist in evaluating the survival potential of
      patients and selecting the most appropriate treatments.

PMID- 20683217
TI  - Anti-inflammatory effects of peritoneal lavage in acute pancreatitis.
AB  - OBJECTIVES: Intraperitoneal administration of trypsin stimulates the production
      of cytokines from peritoneal macrophages. Removing the pancreatitis-associated
      ascitic fluid from the peritoneal cavity may decrease the systemic inflammatory
      response in acute pancreatitis (AP). We investigated the effect of peritoneal
      lavage on the systemic inflammatory response in severe AP. METHODS: Acute
      pancreatitis was induced in Wistar rats by 5% taurocholate intraductal injection.
      Peritoneal lavage was performed for 4 hours after onset of AP. At 4 hours after
      induction of AP, serum samples were assayed for amylase and inflammatory
      cytokines (tumor necrosis factor alpha, interleukin-6 [IL-6], and IL-10).
      Expression of pancreatic cyclooxygenase-2 and inducible nitric oxide synthase,
      liver mitochondrial function, and pulmonary myeloperoxidase activities were
      determined. RESULTS: Peritoneal lavage after AP led to a decrease in serum levels
      of tumor necrosis factor alpha and IL-6 and an increase in IL-10. In the
      pancreas, this treatment reduced cyclooxygenase-2 and inducible nitric oxide
      synthase expression. Liver mitochondrial dysfunction was also reduced. There were
      no differences on serum amylase levels and pulmonary myeloperoxidase between
      groups with AP. CONCLUSIONS: Peritoneal lavage has a systemic anti-inflammatory
      effect in severe AP and may be able to decrease the severity of severe AP.

PMID- 20683218
TI  - Prognostic factors for survival in patients with unresectable pancreatic cancer.
AB  - OBJECTIVES: In patients with unresectable pancreatic cancer, estimation of
      individual prognosis is essential to provide the most suitable biliary stent
      (self-expanding metal stent or plastic stent). The aim of the current study was
      to determine prognostic factors for survival in patients with unresectable
      pancreatic cancer after initial biliary drainage. PATIENTS AND METHODS: The
      current study included 278 patients with unresectable pancreatic cancer.
      Prognostic factors for survival were analyzed using the Cox proportional hazards
      model, the Kaplan-Meier survival estimator, and the Wilcoxon test for difference
      in survival. RESULTS: In univariate analysis, advanced T stage according to the
      TNM classification (P = 0.021, Wald test) and the presence of distant metastases
      (P = 0.001, Wald test) were predictive factors for shorter survival. However, in
      multivariate analysis, the presence of distant metastasis was the only
      independent prognostic factor. The median survival time after initial biliary
      drainage was 3.1 and 6.6 months in patients with and without the presence of
      distant metastases, respectively. CONCLUSIONS: The presence of distant metastases
      was identified as the only independent prognostic factor for survival after
      initial biliary drainage. A self-expanding metal stent should be systematically
      chosen for patient without distant metastases, whereas polyethylene plastic
      stents should be preferred in patients with distant metastases.

PMID- 20683219
TI  - Beta cell mass regulation in the rat pancreas through glucocorticoids and thyroid
      hormones.
AB  - OBJECTIVES: To compare the effects of glucocorticoids and thyroid hormones on the
      regulation of the beta cell mass in the pancreas, the rats were treated and
      analyzed for cell cycle changes in islet and duct cells as a source for beta cell
      neogenesis. METHODS: Different rat pancreases were morphometrically analyzed
      after immunohistochemical staining for markers of proliferation and apoptosis.
      RESULTS: Hydrocortisone increased the beta cell mass of rat pancreases through an
      increase of proliferation. This effect was counteracted by an increase of
      apoptosis. In contrast, thyroxine decreased the beta cell mass through an
      increase of apoptosis. This effect was counteracted by an increased rate of
      proliferation. Combined treatment with both hormones nullified the antagonistic
      effects on proliferation, apoptosis, and beta cell mass, thereby contributing to
      the maintenance of a stable total beta cell volume of the pancreas. CONCLUSIONS:
      Hydrocortisone and thyroxine induced analogous changes in pancreatic duct cells,
      which represent a crucial pool for new beta cells through neogenesis. This may
      explain the positive effects of glucocorticoids in the immunosuppressive therapy
      regimen after whole pancreas transplantation upon long-term insulin independence,
      which is not achievable with isolated islets because of the loss of duct cells
      during the islet process before transplantation.

PMID- 20683220
TI  - Hepatitis B virus infections among children and adolescents in Germany: migration
      background as a risk factor in a low seroprevalence population.
AB  - BACKGROUND: Data on hepatitis B (HB) infection prevalence among children and
      adolescents in Germany are scarce. We estimated seroprevalence of HB infection
      and assessed determinants for HB infection among children and adolescents in
      Germany from a representative population sample. METHODS: From 2003 to 2006, the
      Robert Koch Institute conducted a nationwide cross-sectional Health Interview and
      Examination Survey for Children and Adolescents in Germany. Data on age, gender,
      migration background, and socioeconomic status were collected through
      questionnaires. A child was defined as having a 2-sided migration background if
      both parents, or the child and 1 parent, immigrated, and a 1-sided migration
      background if only 1 parent immigrated. Among children with migration background,
      a first-generation migrant was defined as born outside Germany; a second
      generation migrant was born in Germany. Information on HB vaccination status was
      obtained from vaccination cards. Serologic samples from participants were tested
      for anti-hepatitis B core antigen (anti-HBc) and hepatitis B surface antigen. We
      performed weighted univariable and multivariable logistic regression analyses to
      assess determinants for HB infection. RESULTS: Of 13,065 participants (3-17
      years), 0.5% (95% confidence interval [CI], 0.4-0.7) were anti-HBc positive,
      among whom 38.7% (95% CI, 20.0-57.5) were hepatitis B surface antigen positive.
      Two-sided migration background and being a first- or second-generation migrant
      were significantly associated with anti-HBc positivity (odds ratio [OR]: 8.3, 95%
      CI: 4.0 -17.4; OR: 11.0, 95% CI: 3.5-35.0; OR: 3.0, 95% CI: 1.2-7.3). No further
      determinants were found. CONCLUSIONS: HB infection is rare among children and
      adolescents in Germany. First- and second-generation migrant children can be
      considered to be at risk for HB infection, 2-sided migration background or being
      a first-generation migrant carried the greatest risk. Targeted testing for HB
      infection and early HB vaccination should be provided to immigrants' children.

PMID- 20683221
TI  - New intravenous antibiotics: a focused pharmacotherapy update.

PMID- 20683223
TI  - Venous thrombotic events in children: a challenge for pediatric critical care
      nurses.

PMID- 20683224
TI  - Reducing catheter-associated urinary tract infection in the critical care unit.
AB  - Changes in reimbursement policies have focused attention on the use of indwelling
      catheters in the critical care unit as well as their role in hospital-acquired
      urinary tract infections. Implementation of an evidence-based prevention program
      can significantly reduce both the prevalence of indwelling catheterization and
      the incidence of hospital-acquired catheter-associated urinary tract infection.
      This article describes the epidemiology and pathophysiology of catheter
      associated urinary tract infection, and outlines essential elements of an
      evidence-based prevention program for the critical care unit.

PMID- 20683226
TI  - Introduction. Military critical care nursing: from point of injury to
      rehabilitation.

PMID- 20683227
TI  - Advancing critical care: joint combat casualty research team and joint theater
      trauma system.
AB  - Despite the severity and complexity of injuries, survival rates among combat
      casualties are equal to or better than those from civilian trauma. This article
      summarizes the evidence regarding innovations from the battlefield that
      contribute to these extraordinary survival rates, including preventing hemorrhage
      with the use of tourniquets and hemostatic dressings, damage control
      resuscitation, and the rapid evacuation of casualties via MEDEVAC and the US Air
      Force Critical Care Air Transport Teams. Care in the air for critically injured
      casualties with pulmonary injuries and traumatic brain injury is discussed to
      demonstrate the unique considerations required to ensure safe en route care.
      Innovations being studied to decrease sequelae associated with complex orthopedic
      and extremity trauma are also presented. The role and contributions of the Joint
      Combat Casualty Research Team and the Joint Theater Trauma System are also
      discussed.

PMID- 20683229
TI  - Resuscitation of combat casualties: unique challenges and lessons learned.
AB  - Resuscitation and trauma anesthesia of combat casualties is very similar to
      trauma care in any US hospital--except for the setting. Using case examples, this
      article describes the principles of trauma anesthesia and resuscitation and the
      lessons learned regarding the modifications required when caring for a combat
      casualty. Examples of a massive trauma resuscitation (>10 units of packed red
      blood cells in 24 hours) and burn resuscitation are presented.

PMID- 20683230
TI  - MEDEVAC: critical care transport from the battlefield.
AB  - In current military operations, the survival rates of critically injured
      casualties are unprecedented. An often hidden aspect of casualty care is safe
      transport from the point of injury to a field hospital and subsequently on to
      higher levels of care. This en route critical care, which is provided by flight
      medics under the most austere and rigorous conditions, is a crucial link in the
      care continuum. This article introduces the role and capabilities of US Army
      MEDEVAC and reflects the author's recent experience in Afghanistan as a flight
      medic. This article provides an assessment of the operational issues, medical
      capabilities, and transport experiences to provide a real-world view of critical
      care transport from the battlefield. The MEDEVAC helicopter environment is one of
      the most difficult, if not the most demanding, critical care environments. This
      overview brings to light a small but important piece of the care continuum.

PMID- 20683231
TI  - Measuring critical care air support teams' performance during extended periods of
      duty.
AB  - The Royal Air Force (RAF) Critical Care Air Support Teams (CCASTs) aeromedically
      evacuate seriously injured service personnel. Long casualty evacuation chains
      create logistical constraints that must be considered when aeromedically
      evacuating patients. One constraint is the length of a CCAST mission and its
      potential effect on team member performance. Despite no evidence of patient care
      compromise, the RAF has commissioned a study to investigate whether CCAST mission
      length influences performance. Describing and understanding the role of a CCAST
      enabled fatigue to be defined. Factors essential to studying fatigue were then
      identified that were used to develop a theoretical model for designing a study to
      measure the effects of fatigue on CCAST performance. Relevant factors include the
      patient's clinical condition, team members' cognition and vigilance levels, and
      the occupational aviation environment. Further factors influencing overall
      performance include the duration and complexity of patient interventions, mission
      length, circadian influences, and fatigue countermeasures.

PMID- 20683232
TI  - 7000 miles and 7 days from the battlefield.
AB  - Critically injured combat casualties are rapidly evacuated from the battlefield,
      and within hours of their injuries they begin a 7000-mile journey home, often
      arriving in the United States within 7 days. National Naval Medical Center in
      Bethesda, Maryland, is a major facility for wounded warrior care in the Military
      Health System. Throughout the facility, the staff from a variety of disciplines
      and all military services provides care for military personnel with injuries and
      illnesses, with the goal of optimizing recovery and quality of life. The
      foundational evidence for select aspects of this care is discussed. Innovations
      in training and care delivery include the Air Force Nurse Corps' Critical Care
      Fellowship, the new inpatient Traumatic Brain Injury Unit, and the National
      Intrepid Center for Excellence for Traumatic Brain Injury and Psychological
      Health. The future of the Medical Center includes a new name, expanded staff, and
      newly constructed space by Department of Defense Base Realignment and Closure
      activities.

PMID- 20683233
TI  - Poster presentations: a primer for critical care nurses.

PMID- 20683234
TI  - Systematic assessment of basic pacemaker function.

PMID- 20683236
TI  - Correspondence regarding: thinking outside the box: Alzheimer-type neuropathology
      that does not map directly onto current consensus recommendations. J Neuropathol
      Exp Neurol 2010;69:449-54.

PMID- 20683237
TI  - Effects of ingesting protein in combination with carbohydrate during exercise on
      endurance performance: a systematic review with meta-analysis.
AB  - Coingestion of protein with carbohydrate has been shown to enhance muscle
      recovery, particularly after intense bouts of exercise. However, performance
      benefits of ingesting a protein-carbohydrate drink during exercise remains
      unclear. Therefore, we used a systematic review with meta-analysis to examine the
      influence of protein ingestion during exercise on subsequent endurance
      performance. Eleven qualifying studies were included that contained 3 time-trial
      and 8 time-to-exhaustion cycling protocols. Only 3 of these studies controlled
      for caloric content and contained an isocaloric trial. Of the 11, 4 reported
      significant differences between a control and protein trial; however, none of
      these were isocaloric studies. The 3 time-trial protocols showed no significant
      improvement with protein. The meta-analysis of the time-trial studies revealed no
      significant overall effect (p = 0.73), whereas meta-analysis of time-to
      exhaustion studies revealed a significant effect (p = 0.008). Of the time-to
      exhaustion trials, the isocaloric studies found no significant effect (p = 0.71),
      whereas the isocarbohydrate studies revealed a significant effect (p = 0.05). The
      average percent improvement with ingestion of protein was 9.0%. The
      isocarbohydrate studies reported an improvement of 10.5%, whereas the isocaloric
      studies revealed a 3.4% improvement. We conclude that compared to carbohydrate
      alone, coingestion of protein and carbohydrate during exercise demonstrated an
      ergogenic effect on endurance performance when assessed by time to exhaustion and
      also where supplements were matched for carbohydrate (isocarbohydrate). Thus, the
      ergogenic effect of protein seen in isocarbohydrate studies may be because of a
      generic effect of adding calories (fuel) as opposed to a unique benefit of
      protein. Further research is warranted before a clear conclusion can be drawn.

PMID- 20683240
TI  - Re: Siepe CJ, Hitzl W, Meschede P, et al. Interdependence between disc space
      height, range of motion and clinical outcome in total lumbar disc replacement.
      Spine 2009;34:904-16.

PMID- 20683241
TI  - Fatal left ventricular rupture and pericardial tamponade following a horse kick
      to the chest.
AB  - Horse kicks are rare incidents-especially, if they end in fatality. In this case,
      a 13-year-old girl collapsed 3 minutes after sustaining a kick to the chest from
      a pony. Resuscitation attempts were unsuccessful. Postmortem computed tomography
      and magnetic resonance imaging were performed before autopsy.Imaging revealed a 3
      cm long laceration of the left ventricle and a large pericardial effusion. Using
      segmentation techniques, the amount of blood inside the pericardium was
      determined. These findings correlated well with the autopsy findings. Pericardial
      tamponade was determined at autopsy to be the cause of death.Postmortem imaging
      may prove useful for the diagnosis of these types of injury, but further studies
      are needed to document accuracy.

PMID- 20683242
TI  - Agonal sequences in 14 filmed hangings with comments on the role of the type of
      suspension, ischemic habituation, and ethanol intoxication on the timing of
      agonal responses.
AB  - The Working Group on Human Asphyxia has analyzed 14 filmed hangings: 9 autoerotic
      accidents, 4 suicides, and 1 homicide. The following sequence of agonal responses
      was observed: rapid loss of consciousness in 10 +/- 3 seconds, mild generalized
      convulsions in 14 +/- 3 seconds, decerebrate rigidity in 19 +/- 5 seconds,
      beginning of deep rhythmic abdominal respiratory movements in 19 +/- 5 seconds,
      decorticate rigidity in 38 +/- 15 seconds, loss of muscle tone in 1 minute 17
      seconds +/- 25 seconds, end of deep abdominal respiratory movements in 1 minute
      51 seconds +/- 30 seconds, and last muscle movement in 4 minutes 12 seconds +/- 2
      minutes 29 seconds. The type of suspension and ethanol intoxication does not seem
      to influence the timing of the agonal responses, whereas ischemic habituation in
      autoerotic practitioner might decelerate the late responses to hanging.

PMID- 20683243
TI  - Guidelines to implement medical examiner/coroner-based surveillance for fatal
      infectious diseases and bioterrorism ("Med-X").
AB  - Medical examiners and coroners investigate deaths that are sudden, unexplained,
      and violent. Oftentimes these deaths are a consequence of infections, many of
      which have public health consequences. Additionally, because deaths from
      bioterrorism are homicides, they fall under the jurisdiction of medical examiners
      and coroners. Surveillance for infectious disease-related deaths can enhance the
      opportunities to recognize these deaths. Beginning in 2000, the New Mexico Office
      of the Medical Investigator developed and tested a medical examiner surveillance
      model for bioterrorism and infectious disease mortality ("Med-X") using a set of
      symptoms to determine which cases should receive an autopsy and a set of
      pathology-based syndromes for early reporting of cases to public health
      authorities. This model demonstrated that many of the symptoms had a high
      predictive value for infections and were useful criteria for autopsy performance.
      The causative organism was identified for 81% of infections of which 58% were
      notifiable conditions by public health standards. Uniform criteria for performing
      autopsies and reporting cases to public health authorities enhance surveillance
      for notifiable infectious diseases and increase the probability of recognizing
      fatalities related to bioterrorism. We have developed guidelines for medical
      examiners, coroners and their public health partners to use in implementing Med-X
      surveillance in their jurisdictions. These guidelines encompass definitions of
      symptoms and syndromes, specimen collection and storage procedures, laboratory
      diagnostic approaches, and processes for case flow, case reporting, and data
      collection. We also suggest resources for autopsy biosafety information and
      funding.

PMID- 20683244
TI  - Use of area under the curve to evaluate the effects of antimalarial drugs on
      malaria-associated anemia after treatment.
AB  - To evaluate the effects of antimalarial drugs on Plasmodium falciparum malaria
      associated anemia, we use the area under the curve (AUC) of anemia levels after
      treatment as an approach to combine their duration and magnitude. The method
      involves numeric estimation, by trapezoidal rule, of AUC from a plot of deficit
      in hematocrit levels from 30% (the lower threshold of normal) versus time in
      anemic children. Using the method, we evaluated, in randomized trials, the
      effects of artesunate-mefloquine versus mefloquine alone and artemether
      lumefantrine versus amodiaquine-artesunate on the time course of recovery from
      malaria-associated anemia in 109 children. Anemia resolution times were similar
      (10.9 +/- 6.2 [standard deviation] versus 13.3 +/- 8.9 days, P = 0.2), but mean
      AUC was significantly lower in artesunate-mefloquine- compared with mefloquine
      treated children (35.5 +/- 7.1 [standard error of mean] versus 49.8 +/- 11.3 %.h,
      P = 0.02) indicating larger exposure to anemia in mefloquine-treated children. In
      artemether-lumefantrine- and amodiaquine-artesunate-treated children, both anemia
      resolution times (8.6 +/- 5.3 [standard deviation] versus 8.6 +/- 4.8 days, P =
      0.98) and mean AUC (57.1 +/- 12.9 [standard error of mean] versus 46.3 +/- 8.7
      %.h, P = 0.74) were similar. Estimation of AUC appears more robust than
      estimation of anemia resolution time in evaluating antimalarial drug effects and
      can be used in both observational studies and clinical trials assessing the
      effects of therapies on malaria-associated anemia.

PMID- 20683245
TI  - Recurrent acute stent thrombosis due to allergic reaction secondary to
      clopidogrel therapy.
AB  - Despite significant benefits including mortality advantage demonstrated with
      antiplatelet therapy in large clinical trials, the occurrence of adverse ischemic
      events, including stent thrombosis after percutaneous coronary intervention has
      been the challenging and devastating complication. Clopidogrel as a monotherapy,
      or more common in combination with aspirin, represents a cornerstone of modern
      pharmacotherapy in the invasive era. Although vigilance in maintenance of this
      dual antiplatelet treatment is mandatory, obligatory cessation of one of these
      agents can be observed in rare circumstances of adverse events. We describe a
      patient who developed recurrent acute stent thrombosis associated with
      clopidogrel-induced allergic reaction and discuss our therapeutic considerations.

PMID- 20683246
TI  - Resident/fellow evaluation of clinical teaching: an essential ingredient of
      effective teacher development and educational planning.

PMID- 20683247
TI  - Leukocyte chemotaxis and migration: can we follow the cells?

PMID- 20683248
TI  - Ketamine for managing perioperative pain in opioid-dependent patients with
      chronic pain: a unique indication?

PMID- 20683249
TI  - Should anesthesiologists be equipped as genetic counselors?

PMID- 20683251
TI  - Effects of preoxygenation on desaturation time during hemorrhagic shock in pigs.
AB  - BACKGROUND: Patients in hemorrhagic shock often require emergent airway
      management. Clinical experience suggests that oxygen desaturation occurs rapidly
      in these patients; however, data are scant. The hypothesis of this study was that
      increasing levels of hemorrhagic shock, varying levels of fraction of inspired
      oxygen (Fio2) for preoxygenation, and fluid resuscitation significantly affect
      the duration until critical desaturation occurs. METHODS: Fifteen pigs were
      studied in a hemorrhagic shock model with controlled hemorrhage (15, 30, and 45
      ml/kg blood loss) and randomized to standard fluid resuscitation or no fluids. At
      each shock level, three apnea experiments (in randomized order) were performed
      after 5 min of preoxygenation at 21, 50, or 100% Fio2. After preoxygenation,
      ventilation was discontinued and the time to peripheral oxygen saturation of 70%
      or less was measured. RESULTS: During normovolemia, peripheral oxygen
      desaturation to less than 70% occurred after 33+/-7 s (Fio2=0.21, mean+/-SD),
      89+/-12 s (Fio2=0.5), and 165+/-22 s (Fio2=1.0; P<0.001). During increasing blood
      loss, peripheral oxygen desaturation to Spo2 less than 70% occurred significantly
      (P<0.001) faster compared with normovolemia, but no effect of fluid resuscitation
      was observed. With 45 ml/kg blood loss, peripheral oxygen desaturation to less
      than 70% occurred after approximately 15 (Fio2=0.21) to 65 (Fio2=0.5) to 140 s
      (Fio2=1.0). CONCLUSIONS: Findings from this swine hemorrhagic shock model confirm
      that Fio2 and the level of hemorrhagic shock, but not fluid resuscitation,
      influence the rate of apneic desaturation. A five-fold increase in time until
      critical oxygen desaturation occurs can be achieved when preoxygenating with 100%
      oxygen compared with room air, underscoring the importance of adequate
      preoxygenation before emergent airway management.

PMID- 20683250
TI  - Toll-like receptor 4-myeloid differentiation factor 88 signaling contributes to
      ventilator-induced lung injury in mice.
AB  - BACKGROUND: The mechanisms of ventilator-induced lung injury, an iatrogenic
      inflammatory condition induced by mechanical ventilation, are not completely
      understood. Toll-like receptor 4 (TLR4) signaling via the adaptor protein myeloid
      differentiation factor 88 (MyD88) is proinflammatory and plays a critical role in
      host immune response to invading pathogen and noninfectious tissue injury. The
      role of TLR4-MyD88 signaling in ventilator-induced lung injury remains
      incompletely understood. METHODS: Mice were ventilated with low or high tidal
      volume (HTV), 7 or 20 ml/kg, after tracheotomy for 4 h. Control mice were
      tracheotomized without ventilation. Lung injury was assessed by: alveolar
      capillary permeability to Evans blue albumin, wet/dry ratio, bronchoalveolar
      lavage analysis for cell counts, total proteins and cytokines, results of
      histopathological examination of the lung, and plasma cytokine levels. RESULTS:
      Wild-type mice subjected to HTV had increased pulmonary permeability,
      inflammatory cell infiltration/lung edema, and interleukin-6/macrophage
      inflammatory protein-2 in the lavage compared with control mice. In HTV, levels
      of inhibitor of kappaB alpha decreased, whereas phosphorylated extracellular
      signal-regulated kinases increased. TLR4 mutant and MyD88 mice showed markedly
      attenuated response to HTV, including less lung inflammation, pulmonary edema,
      cell number, protein content, and the cytokines in the lavage. Furthermore,
      compared with wild-type mice, both TLR4 mutant and MyD88 mice had significantly
      higher levels of inhibitor of kappaB alpha and reduced extracellular signal
      regulated kinase phosphorylation after HTV. CONCLUSIONS: TLR4-MyD88 signaling
      plays an important role in the development of ventilator-induced lung injury in
      mice, possibly through mechanisms involving nuclear factor-kappaB and mitogen
      activated protein kinase pathways.

PMID- 20683252
TI  - Increased pulmonary venous resistance in morbidly obese patients without daytime
      hypoxia: clinical utility of the pulmonary artery catheter.
AB  - BACKGROUND: The pulmonary artery (PA) diastolic-pulmonary capillary wedge
      pressure (PAD-PCWP) gradient has been shown to be increased in morbidly obese
      patients without daytime hypoxia. In sepsis, the increased pulmonary venous
      resistance (PvR) contributes to increases in PAD-PCWP gradient. In addition, the
      obesity-related endotoxemia is known to be involved in the pathophysiology of
      metabolic syndrome in obesity. Therefore, it is possible that the increased PvR
      contributes to increases in PAD-PCWP gradient in morbid obesity. We examined this
      possibility. METHODS: Included were 25 obese patients without daytime hypoxia
      undergoing bariatric surgery under general anesthesia. PvR was calculated as the
      difference between mean PA output pressure and PCWP divided by cardiac index.
      Mean PA output pressure was computed from the harmonic form of the recorded PA
      pressure by applying an attenuating factor to its phasic components, for which
      Fourier analysis was used. Total pulmonary vascular resistance (TPVR) was
      calculated as the difference between mean PA pressure and PCWP divided by cardiac
      index. To avoid the effect of PA resistance on TPVR and PvR, the PvR/TPVR ratio
      was used. RESULTS: There was a good correlation between PvR/TPVR ratio and PAD
      PCWP gradient (r2=0.785, P<0.0001). When patients were divided into two groups
      based on PAD-PCWP gradient, the PvR/TPVR ratio was 0.67+/-0.06 (mean+/-SD) in the
      group with a PAD-PCWP gradient of at least 6 mmHg and 0.48+/-0.05 in the other
      group (P<0.0001). CONCLUSIONS: A strong correlation between PvR/TPVR ratio and
      PAD-PCWP gradient suggests that the increased PvR contributes to increased PAD
      PCWP gradient in obese patients without daytime hypoxia.

PMID- 20683253
TI  - Potential influence of the anesthetic technique used during open radical
      prostatectomy on prostate cancer-related outcome: a retrospective study.
AB  - BACKGROUND: Recently published studies suggest that the anesthetic technique used
      during oncologic surgery affects cancer recurrence. To evaluate the effect of
      anesthetic technique on disease progression and long-term survival, we compared
      patients receiving general anesthesia plus intraoperative and postoperative
      thoracic epidural analgesia with patients receiving general anesthesia alone
      undergoing open retropubic radical prostatectomy with extended pelvic lymph node
      dissection. METHODS: Two sequential series were studied. Patients receiving
      general anesthesia combined with epidural analgesia (January 1994-June 1997,
      n=103) were retrospectively compared with a group given general anesthesia
      combined with ketorolac-morphine analgesia (July 1997-December 2000, n=158).
      Biochemical recurrence-free survival, clinical progression-free survival, cancer
      specific survival, and overall survival were assessed using the Kaplan-Meier
      technique and compared using a multivariate Cox-proportional-hazards regression
      model and an alternative model with inverse probability weights to adjust for
      propensity score. RESULTS: Using propensity score adjustment with inverse
      probability weights, general anesthesia combined with epidural analgesia resulted
      in improved clinical progression-free survival (hazard ratio, 0.45; 95%
      confidence interval, 0.27-0.75, P=0.002). No significant differences in the two
      groups were found for biochemical recurrence-free survival, cancer-specific
      survival, or overall survival. Higher preoperative serum values for prostate
      specific antigen, specimen Gleason score of at least 7, non-organ-confined tumor
      stage, and positive lymph node status were independent predictors of biochemical
      recurrence-free survival. CONCLUSIONS: General anesthesia with epidural analgesia
      was associated with a reduced risk of clinical cancer progression. However, no
      significant difference was found between general anesthesia plus postoperative
      ketorolac-morphine analgesia and general anesthesia plus intraoperative and
      postoperative thoracic epidural analgesia in biochemical recurrence-free
      survival, cancer-specific survival, or overall survival.

PMID- 20683254
TI  - N-acetylcysteine protects against bupivacaine-induced myotoxicity caused by
      oxidative and sarcoplasmic reticulum stress in human skeletal myotubes.
AB  - BACKGROUND: Local anesthetics offer the benefits of extended analgesia with
      greater patient satisfaction and faster rehabilitation compared with intravenous
      morphine. These benefits, however, can be offset by adverse iatrogenic muscle
      pain. Here, the authors investigate the mechanisms of local anesthetic-induced
      myotoxicity and assess the protective effect of N-acetylcysteine. METHODS: The
      authors used primary cell cultures of human skeletal muscle myoblasts to study
      local anesthetic adverse effects. Production of reactive oxygen species was
      investigated in human skeletal myotubes by fluorescence microscopy. Expression of
      sarcoplasmic/endoplasmic reticulum stress markers and induction of apoptosis were
      followed by immunofluorescence and Western blot analysis. Finally, the effect of
      N-acetylcysteine on bupivacaine-induced myotoxicity was investigated in vitro.
      RESULTS: Bupivacaine sequentially induced reactive oxygen species production,
      oxidative stress, sarcoplasmic/endoplasmic reticulum stress, and activation of
      caspases 9 and 7 in human differentiated myoblasts. These iatrogenic effects were
      prevented by N-acetylcysteine. CONCLUSIONS: The authors demonstrated a protective
      effect of N-acetylcysteine against bupivacaine-induced sarcoplasmic/endoplasmic
      reticulum stress and apoptosis in primary human skeletal muscle cell.

PMID- 20683255
TI  - Metabolic profiling of hearts exposed to sevoflurane and propofol reveals
      distinct regulation of fatty acid and glucose oxidation: CD36 and pyruvate
      dehydrogenase as key regulators in anesthetic-induced fuel shift.
AB  - BACKGROUND: Myocardial energy metabolism is a strong predictor of postoperative
      cardiac function. This study profiled the metabolites and metabolic changes in
      the myocardium exposed to sevoflurane, propofol, and Intralipid and investigated
      the underlying molecular mechanisms. METHODS: Sevoflurane (2 vol%) and propofol
      (10 and 100 microM) in the formulation of 1% Diprivan (AstraZeneca Inc.,
      Mississauga, ON, Canada) were compared for their effects on oxidative energy
      metabolism and contractility in the isolated working rat heart model. Intralipid
      served as a control. Substrate flux through the major pathways for adenosine
      triphosphate generation in the heart, that is, fatty acid and glucose oxidation,
      was measured using [H]palmitate and [C]glucose. Biochemical analyses of
      nucleotides, acyl-CoAs, ceramides, and 32 acylcarnitine species were used to
      profile individual metabolites. Lipid rafts were isolated and used for Western
      blotting of the plasma membrane transporters CD36 and glucose transporter 4.
      RESULTS: Metabolic profiling of the hearts exposed to sevoflurane and propofol
      revealed distinct regulation of fatty acid and glucose oxidation. Sevoflurane
      selectively decreased fatty acid oxidation, which was closely related to a marked
      reduction in left ventricular work. In contrast, propofol at 100 microM but not
      10 microM increased glucose oxidation without affecting cardiac work. Sevoflurane
      decreased fatty acid transporter CD36 in lipid rafts/caveolae, whereas high
      propofol increased pyruvate dehydrogenase activity without affecting glucose
      transporter 4, providing mechanisms for the fuel shifts in energy metabolism.
      Propofol increased ceramide formation, and Intralipid increased hydroxy
      acylcarnitine species. CONCLUSIONS: Anesthetics and their solvents elicit
      distinct metabolic profiles in the myocardium, which may have clinical
      implications for the already jeopardized diseased heart.

PMID- 20683256
TI  - Images in anesthesiology: transient paraplegia after anesthesia for magnetic
      resonance imaging.

PMID- 20683257
TI  - Relative deficiency of arginine vasopressin in children after cardiopulmonary
      bypass.
AB  - OBJECTIVE: To describe changes in plasma arginine vasopress in concentration in
      children following cardiopulmonary bypass and determine whether, in some
      patients, plasma arginine vasopressin remains relatively low despite hemodynamic
      instability. DESIGN: Prospective observational study. SETTING: Pediatric
      intensive care unit at a tertiary care university hospital. PATIENTS: One hundred
      twenty patients <= 18 yrs of age undergoing open heart surgery requiring
      cardiopulmonary bypass at Children's Hospital of Michigan between January 2008
      and January 2009. INTERVENTIONS: Blood samples were collected before
      cardiopulmonary bypass and 4, 24, and 48 hrs after cardiopulmonary bypass for
      measurement of plasma arginine vasopressin concentration. MEASUREMENTS AND MAIN
      RESULTS: Mean plasma arginine vasopressin (pg/mL) for all patients was 21 +/- 63
      before cardiopulmonary bypass and 80 +/- 145, 43 +/- 79, and 19 +/- 25 at 4, 24,
      and 48 hrs, respectively, after cardiopulmonary bypass. Patients with plasma
      arginine vasopressin below the lower quartile (< 9.2 pg/mL) at 4 hrs after
      cardiopulmonary bypass (n = 29), labeled group A, were examined separately and
      compared with the rest of the study population, labeled group B. Mean plasma
      arginine vasopressin was 4.9 +/- 2.6 in group A at 4 hrs after cardiopulmonary
      bypass, statistically unchanged from its baseline mean plasma arginine
      vasopressin of 5.0 +/- 10.4 (p = .977). Mean plasma arginine vasopressin in group
      B was 104 +/- 160 at 4 hrs after cardiopulmonary bypass. Mean plasma arginine
      vasopressin of group A was also significantly lower as compared with group B
      before and 24 and 48 hrs after cardiopulmonary bypass. Hemodynamics, inotrope
      score, and serum sodium did not differ between groups at any time point. Plasma
      arginine vasopressin was measured immediately before exogenous arginine
      vasopressin administration in 10 patients; only those (n = 3) with hemodynamic
      instability and relatively low plasma arginine vasopressin concentration (< 9.2
      pg/mL) had notable hemodynamic improvement. CONCLUSIONS: In some children
      undergoing open heart surgery, plasma arginine vasopressin concentration is
      relatively low at baseline and remains low after cardiopulmonary bypass
      regardless of hemodynamic stability and serum osmolality. These children are
      likely the optimal candidates for exogenous arginine vasopressin should
      hemodynamic compromise occur.

PMID- 20683258
TI  - Effect of continuous compressions and 30:2 cardiopulmonary resuscitation on
      global ventilation/perfusion values during resuscitation in a porcine model.
AB  - OBJECTIVE: Rescue ventilations during bystander resuscitation, although
      previously considered essential, interrupt the continuity of chest compressions
      and might have deleterious effects in basic life support. This study was
      undertaken to analyze the global ventilation/perfusion values of continuous
      compressions and 30:2 cardiopulmonary resuscitation to determine the
      effectiveness for each approach in a porcine model of prolonged bystander
      cardiopulmonary resuscitation for ventricular fibrillation. DESIGN: Prospective,
      randomized animal study. SETTING: A university animal research laboratory.
      SUBJECTS: Twenty-four male domestic pigs (n = 12/group) weighing 30 +/- 2 kg.
      INTERVENTIONS: All animals had ventricular fibrillation induced by programmed
      electrical stimulation instruments and were randomized into two groups.
      Continuous compressions or 30:2 compression/rescue ventilation cardiopulmonary
      resuscitation was performed in each group. MEASUREMENTS AND MAIN RESULTS:
      Continuous respiratory variables, hemodynamic parameters, and blood gas analysis
      outcomes were recorded, and global ventilation/perfusion values were calculated.
      Alveolar minute volume and global ventilation/perfusion values decreased
      progressively after ventricular fibrillation, but cardiac output was stable. The
      global ventilation/perfusion value was higher in the ventilation cardiopulmonary
      resuscitation group than that in the continuous compression group (p < .0001) and
      was higher than normal. Coronary perfusion pressure was progressively decreased
      after 6 mins of cardiopulmonary resuscitation and greatly fluctuated in the
      ventilation cardiopulmonary resuscitation group. Coronary perfusion pressure was
      higher in the continuous compression group than that in the ventilation
      cardiopulmonary resuscitation group after 9 mins of cardiopulmonary resuscitation
      (p < .05). Values for pH and Pao2 progressively decreased, but there were no
      significant differences between the two groups, except for pH at 12 mins of
      cardiopulmonary resuscitation and Paco2 after 3 mins of cardiopulmonary
      resuscitation. CONCLUSIONS: In the first 12 mins of cardiopulmonary
      resuscitation, continuous compressions could maintain relatively better coronary
      perfusion pressure, Pao2, and global ventilation/perfusion values than 30:2
      cardiopulmonary resuscitation. Therefore, rescue ventilation during 12 mins of
      simulated bystander cardiopulmonary resuscitation did not improve hemodynamics or
      outcomes compared with compression-only cardiopulmonary resuscitation.

PMID- 20683259
TI  - Hypoproteinemia does not alter plasma volume expansion in response to a 0.9%
      saline bolus in awake sheep.
AB  - OBJECTIVE: To test the hypothesis that hypoproteinemia reduces plasma volume
      expansion produced by a bolus of crystalloid solution given to awake sheep.
      DESIGN: Prospective and observational. SETTING: Laboratory. SUBJECTS: Five female
      merino sheep (n = 5) weighing 37 +/- 3 kg were anesthetized. INTERVENTIONS: Each
      animal was subjected to a 5-day test period: day 1: 50 mL/min 0.9% saline
      infusion over 20 mins. Days 2-4: daily plasmapheresis and replacement of the shed
      plasma with 6 L of 0.9% saline were performed in increments. MEASUREMENTS AND
      MAIN RESULTS: Fractional plasma volume expansion after rapid infusion of saline
      on days 1 and 5 was calculated from changes in hemoglobin concentration. There
      was a significant reduction in total plasma protein concentration after
      plasmapheresis (p < .05). Colloid osmotic pressures were also significantly
      lowered (p < .05). A crystalloid infusion of 0.9% saline did not alter any of
      these values compared with baseline. The hemodynamic measurements did not show
      significant differences between the experiments. The plasma volume expansion
      reached approximately 20% at the end of infusion and stayed at 10-15% during the
      experiments. No difference was found in plasma volume expansion produced by a
      bolus of 50 mL/min of 0.9% in the hypoproteinemic state when compared with the
      euproteinemic state (p = .61). No difference in cumulative urinary output was
      found between the two states. CONCLUSIONS: In contrast to our hypothesis, severe
      acute hypoproteinemia does not reduce plasma volume expansion in response to 50
      mL/min 0.9% saline infusion in nonspleenectomized sheep when compared with the
      resultant plasma volume expansion after a 50 mL/min of 0.9% infusion in the
      euproteinemic state.

PMID- 20683261
TI  - Travelers' diarrhea.
AB  - PURPOSE OF REVIEW: Travelers' diarrhea affects 20-60% of travelers to low-income
      regions of the world. Much of the evidence for the clinical description and
      management of travelers' diarrhea was generated years ago, however, there is new
      information on geographic and host risk, etiology, and prevention strategies.
      RECENT FINDINGS: Travel to South Asia, followed by sub-Saharan Africa and South
      America, carries the highest risk for diarrheal syndromes in returned travelers.
      Women are more susceptible to travel-related diarrhea than men. Host genetic
      studies have demonstrated that single nucleotide polymorphisms in the
      lactoferrin, osteoprotegerin, and IL-10 genes are associated with small but
      increased risks for diarrhea and enteric pathogens. Enterotoxigenic Bacteroides
      fragilis is likely to be a new agent identified as causing travelers' diarrhea,
      and heat-stable toxin-producing Escherichia coli appears to be more common than
      heat-labile toxin E. coli. Overall levels of sanitation at the travel
      destination, including individual eating establishments, are strong predictors
      for acquisition of travelers' diarrhea. A new transdermal LT vaccine shows
      promise in modifying the severity of travelers' diarrhea. It remains uncertain
      whether prophylaxis or prompt self-treatment of travelers' diarrhea will prevent
      late-onset irritable bowel syndrome. For self-treatment, azithromycin is the drug
      of choice in travelers to areas where there is a high risk of fluoroquinolone
      resistant Campylobacter spp., such as South and Southeast Asia and possibly North
      Africa, Central and South America. SUMMARY: There is increased understanding of
      the determinants of travelers' diarrhea. Despite this travelers' diarrhea remains
      one of the most common illnesses in travelers. Continued focus on intervention
      strategies may ultimately lead to decreased incidence.

PMID- 20683260
TI  - Methicillin-resistant Staphylococcus aureus nasal colonization is a poor
      predictor of intensive care unit-acquired methicillin-resistant Staphylococcus
      aureus infections requiring antibiotic treatment.
AB  - OBJECTIVE: To test whether intensive care unit (ICU) nasal screening for
      methicillin-resistant Staphylococcus aureus (MRSA) predicts the presence or
      absence of MRSA infections requiring antimicrobial treatment. DESIGN: A
      prospective cohort study. SETTING: Medical ICU at Barnes-Jewish Hospital, a 1252
      bed urban teaching hospital. PATIENTS: Seven hundred forty-nine consecutive
      patients admitted to the medical ICU over a 7-mo period (November 2007 through
      June 2008). INTERVENTIONS: Nasal swabs were obtained at ICU admission and weekly
      thereafter for MRSA detection by using polymerase chain reaction. All subjects
      were followed for the development of MRSA infection during their ICU stay.
      MEASUREMENTS AND MAIN RESULTS: One hundred sixty-four (21.9%) patients had
      positive nasal colonization with MRSA at the time of ICU admission. The
      predictive accuracy of MRSA nasal colonization for ICU-acquired MRSA infections,
      either lower respiratory tract infection or bloodstream infection, was poor
      (lower respiratory tract infection: sensitivity, 24.2%; specificity, 78.5%;
      positive predictive value, 17.7%; and negative predictive value, 84.4%; and
      bloodstream infection: sensitivity, 23.1%; specificity, 78.2%; positive
      predictive value, 11.0%; and negative predictive value, 89.7%). Addition of nasal
      colonization results obtained during the ICU stay did not appreciably change the
      predictive accuracy of this test for identification of subsequent lower
      respiratory tract infections and bloodstream infections attributed to MRSA
      requiring antimicrobial treatment. CONCLUSIONS: In this analysis, nasal
      colonization with MRSA was found to be a poor predictor for the subsequent
      occurrence of MRSA lower respiratory tract infections and MRSA bloodstream
      infections requiring antimicrobial treatment. Clinicians should be cautious in
      using the results of nasal-colonization testing to determine the need for MRSA
      treatment among patients with ICU-acquired infections.

PMID- 20683262
TI  - Hepatitis E in high-income countries.
AB  - PURPOSE OF REVIEW: To discuss recent advances in characterising viral Hepatitis E
      (HEV) in nonendemic regions, with a special focus on epidemiology in high-income
      countries, different clinical aspects of the disease, possible zoonotic origin of
      these cases and the improvement of Hepatitis E diagnosis. RECENT FINDINGS: In
      high-income countries, most cases of Hepatitis E are acquired locally and not
      imported from endemic regions. Different genotypes are involved in indigenous
      cases than those in endemic regions. Particular population groups, such as
      transplant recipients, can be persistently infected by hepatitis E and develop
      chronic diseases. Viral hepatitis E is frequently observed in people in animal
      care occupations. Indeed, HEV has a large animal reservoir and this emerging
      disease in developed countries has probably a zoonotic origin. SUMMARY: Recent
      studies on viral Hepatitis E have shown that the epidemiology of the disease
      differs between endemic and nonendemic regions. Several lines of evidence suggest
      that Hepatitis E is more frequent than was suspected and that it has a possible
      animal origin. Particular attention must be paid to the possible chronic
      evolution of various forms of the disease. Surveillance of human cases and animal
      reservoirs must be developed further.

PMID- 20683263
TI  - Newer diagnostic approaches to intestinal protozoa.
AB  - PURPOSE OF REVIEW: To update the reader on the latest developments in the
      laboratory diagnosis of intestinal protozoa. RECENT FINDINGS: Correct
      identification of a diarrhoea causing pathogens is essential for the choice of
      treatment in an individual patient as well as to map the aetiology of diarrhoea
      in a variety of patient populations. Classical diagnosis of diarrhoea causing
      protozoa by microscopic examination of a stool sample lacks both sensitivity and
      specificity. Alternative diagnostic platforms are discussed. SUMMARY: Recent
      literature on the diagnosis of intestinal protozoa has focused mainly on nucleic
      acid-based assays, in particular the specific detection of parasite DNA in stool
      samples using real-time PCR. In addition, the trend has been moving from single
      pathogen detection to a multiplex approach, allowing simultaneous identification
      of multiple parasites. Different combinations of targets can be used within a
      routine diagnostic setting, depending on the patient population, such as
      children, immunocompromised individuals and those who have been travelling to
      tropical regions. Large-scale monitoring and evaluation of control strategies
      become feasible due to automation and high-throughput facilities. Improved
      technology also has become available for differentiating protozoa subspecies,
      which facilitates outbreak investigations and extensive research in molecular
      epidemiology.

PMID- 20683264
TI  - Update on the diagnosis and treatment of food-borne trematode infections.
AB  - PURPOSE OF REVIEW: More than 40 million people are affected by food-borne
      trematode infections. Diagnosis is unsatisfactory and there are only two drugs
      available for treatment and control: praziquantel and triclabendazole. This
      review provides an update on recent developments in the diagnosis and treatment
      of food-borne trematodiases. RECENT FINDINGS: The trematocidal properties of
      tribendimidine and peroxidic drugs (e.g. artemisinins and synthetic trioxolanes)
      have been characterized, including in-vitro and in-vivo studies, elucidating
      structure-activity relationships and pharmacokinetics and their efficacies have
      been evaluated in large animal models. Tribendimidine achieved high worm burden
      reductions against Opisthorchis viverrini and Clonorchis sinensis harboured in
      rodents and the antimalarial drug mefloquine showed promising opisthorchicidal
      activity in vivo. Advances have been made with immunological and molecular
      diagnostics. Metabolic profiling investigations in rodents experimentally
      infected with Fasciola hepatica and Echinostoma caproni yielded parasite-specific
      candidate biomarkers, which might give rise to novel diagnostic targets. The
      FLOTAC technique showed a higher sensitivity and efficiency for detecting F.
      hepatica eggs in rat faecal samples than the sedimentation method. SUMMARY:
      Progress has been registered with trematocidal drug candidates that need to be
      studied in greater detail preclinically, with the most promising ones progressing
      into proof-of-concept trials. Drug development research should go hand-in-hand
      with innovation and application into new and improved diagnostic tools.

PMID- 20683265
TI  - Clinical features and treatment of alveolar echinococcosis.
AB  - PURPOSE OF REVIEW: Human alveolar echinococcosis is caused by the larval stage of
      Echinococcus multilocularis, occurring in at least 42 countries of the northern
      hemisphere. Recent studies in Europe and Asia have shown that the endemic area of
      E. multilocularis is larger than previously known and the parasite has regionally
      expanded from rural to urban areas. Diagnosis of alveolar echinococcosis is
      supported by results from imaging studies, histopathology and/or nucleic acid
      detection, and serology. The present review summarizes current understanding of
      clinical features, knowledge on appropriate treatment, and discusses ways to
      improve standards of care. RECENT FINDINGS: High prevalences of this deadly
      disease have been discovered in surveys in parts of China. Clinical
      manifestations, diagnostic tools and the burden of disease were described, and
      are based on high case numbers. In Europe, excellent tools have been introduced,
      which improve disease management. Long-term observations in Switzerland provide
      an optimistic view, as the infection can be well controlled, if patients are
      cared for in specialized centres. An expert consensus summarizes the current
      recommendation for diagnosis and treatment of alveolar echinococcosis by the
      Informal Working Group on Echinococcosis of the WHO. SUMMARY: Diagnosis and
      treatment of alveolar echinococcosis remains a challenge for clinicians. The
      updated WHO-recommendations aim to support decisions on diagnosis and treatment
      of alveolar echinococcosis. Anti-infective therapy is the backbone of treatment;
      surgery should be restricted to patients at an early stage of the disease. For
      the majority of cases continuous chemoprophylaxis with benzimidazoles is cost
      effective and leads to a good quality of life for patients with this chronic
      disease.

PMID- 20683266
TI  - Controversies in the treatment of Burkitt lymphoma in AIDS.
AB  - PURPOSE OF REVIEW: The success of combined antiretroviral therapy (cART) has
      transformed HIV infection into a survivable chronic disease in developed
      countries. Increasingly then, the risks of HIV associated cancers become
      paramount. Burkitt lymphoma is one of the cancer subtypes highly
      disproportionately affecting HIV infected patients. RECENT FINDINGS: Recent
      conference proceedings appear to corroborate early reports that intensive therapy
      of HIV-Burkitt lymphoma is feasible and effective. An optimal approach is not
      defined due to the small numbers of patients in current trials and the absence of
      comparison studies. Moreover, as breakthroughs in the pathogenesis of lymphoma in
      general and Burkitt lymphoma in particular suggest that HIV infection plays a
      significant role, the opportunity for targeted therapy based on differences in
      biology are wholly untapped. SUMMARY: Advances are being made in HIV-Burkitt
      lymphoma, but future studies need to incorporate our expanding understanding of
      biology to improve efficacy and reduce toxicity, preferably by integrating a
      biologic approach to this curable disease.

PMID- 20683267
TI  - Histone deacetylase inhibitors in lymphoma.
AB  - PURPOSE OF REVIEW: Although many advances have been made in the treatment of
      lymphoma in the past decade, the treatment of patients with relapsed and
      refractory disease remains challenging. Only a fraction of patients will be cured
      with salvage therapy and transplantation. For those patients that are either
      ineligible or relapse after transplant, the treatment options are limited. This
      illustrates the need for new drugs and novel treatment strategies. This review
      will focus on the emerging role of histone deacetylase inhibitors (HDACis) in
      patients with relapsed lymphoma. RECENT FINDINGS: Several HDACis have been
      evaluated in relapsed and refractory Hodgkin and non-Hodgkin lymphoma showing
      promising activity in both. Specifically, vorinostat and romidepsin have been
      approved by the US Food and Drug Administration for patients with relapsed or
      refractory cutaneous T-cell lymphoma. Several other HDACis have shown very
      promising activity in Hodgkin lymphoma including panobinostat, entinostat and
      mocetinostat. SUMMARY: With the limited options available for lymphoma patients
      in the relapsed and refractory setting, the efficacy demonstrated by HDACis in
      this patient population is exciting and much needed and will hopefully prompt
      further investigation into additional agents and into the combination with
      HDACis.

PMID- 20683268
TI  - Role of early PET in the management of diffuse large B-cell lymphoma.
AB  - PURPOSE OF REVIEW: This article reviews the role of interim fluorine-18
      fluorodeoxyglucose (FDG)-PET in the management of aggressive non-Hodgkin
      lymphoma. RECENT FINDINGS: In the diagnosis of diffuse large B-cell lymphoma, FDG
      PET has proved to be a highly sensitive imaging modality. SUMMARY: The
      specificity of 18FDG-PET is improved with the addition of computed tomography
      (CT) and combined PET/CT is now considered a standard staging procedure for
      aggressive lymphoma. In addition, residual FDG positivity at the end of therapy
      is strongly predictive for inferior survival and has been incorporated into
      revised response criteria for aggressive lymphoma. With the established
      prognostic value of PET/CT both before and after therapy, interest has now turned
      to whether interim FDG-PET could be an early indicator of tumor sensitivity.
      Current clinical trials are now focused on clarifying the role of PET/CT in the
      early distinction between good and poor responders to standard
      immunochemotherapy. The interest in such early patient selection assumes that a
      rapid metabolic response to standard immunochemotherapy predicts a better
      therapeutic response and survival, and that nonresponders may benefit from an
      early change in therapy. Preliminary data suggested that interim PET could
      identify the early presence of such residual disease. However, recent
      publications are hindered by important variances in patient populations and
      treatment protocols, the timing and methodology of scans, the reporting criteria
      used to assess response, and the reproducibility of reporting in accordance with
      these criteria. Questions remain on the utility of FDG-PET in this indication.

PMID- 20683269
TI  - Peripheral T-cell lymphoma: autologous hematopoietic cell transplantation as
      first-line therapy.
AB  - PURPOSE OF REVIEW: The peripheral T-cell lymphomas (PTCL) are a heterogeneous
      group of non-Hodgkin's lymphomas associated with an unfavorable prognosis
      compared with the B-cell non-Hodgkin's lymphomas. The PTCLs are characterized by
      high remission rates after frontline therapy, but relapse inevitably occurs. The
      impact of high-dose chemotherapy with autologous hematopoietic cell
      transplantation (AHCT) as early consolidation therapy will be the focus of this
      review. RECENT FINDINGS: In several prospective trials, only PTCL patients with
      responsive disease after induction chemotherapy proceeded to AHCT. The
      progression-free survivals ranged from 30% to 40% with low toxicity. The outcomes
      in retrospective trials appear more favorable but such trials were affected by a
      selection bias because only chemosensitive patients actually proceeded to AHCT,
      whereas the prospective studies were intention-to-treat analyses. Most of the
      published trials demonstrated that prognostic models such as the International
      Prognostic Index and the Prognostic Index for T-cell lymphoma help predict
      outcome after AHCT. SUMMARY: Current data support the use of AHCT as early
      consolidation therapy for PTCL patients who are chemosensitive after induction
      chemotherapy. However, approximately one-third of patients are early induction
      failures and thus are not able to proceed to AHCT. Additionally, disease relapse
      remains the leading cause of treatment failure after AHCT, and thus more
      intensive treatment strategies or better noncross-resistant therapies are greatly
      needed early in the course of the disease.

PMID- 20683270
TI  - Pharmacokinetics and bioavailability of an integrase and novel pharmacoenhancer
      containing single-tablet fixed-dose combination regimen for the treatment of HIV.
AB  - OBJECTIVE: This study evaluated the relative bioavailability and pharmacokinetics
      of elvitegravir (EVG), emtricitabine (FTC), tenofovir disoproxil fumarate (TDF),
      and a investigational pharmacoenhancer, cobicistat (GS-9350, COBI) coformulated
      as a fixed-dose combination tablet (FDC) compared with ritonavir-boosted EVG and
      FTC + TDF in healthy subjects. METHODS: Subjects were randomized to 1 of 2
      sequences. All treatments were administered in the morning for 10 days with food,
      separated by a 2-day washout. Blood samples were collected over 24 hours with the
      last dose of each treatment. RESULTS: Forty-four subjects enrolled, 42 subjects
      completed all periods. All study treatments were generally well tolerated.
      Relative to ritonavir-boosted EVG, the geometric least-squares means ratios (GMR)
      [90% confidence interval (CI)] for EVG area under plasma concentration-time curve
      from time zero until the end of the dosing interval (AUC)tau, maximum
      concentration (Cmax), and trough concentration (Ctau) were 118 (110 to 126), 108
      (100 to 116), and 110 (95.3 to 127), respectively, with EVG/COBI 150 mg/FTC/TDF.
      Relative to FTC + TDF, FTC GMR, and 90% CI were 127 (115 to 140) for AUCtau, 121
      (107 to 137) for Cmax, and 126 (118 to 136) for Ctau; tenofovir (TFV) GMR and 90%
      CI were 118 (114 to 122), 130 (122 to 138), and 124 (119 to 129) for AUCtau,
      Cmax, and Ctau, respectively, with EVG/COBI 150 mg/FTC/TDF. CONCLUSIONS: Fixed
      dose combination tablet containing COBI 150 mg resulted in desired high EVG Ctau
      concentrations and clinically equivalent tenofovir and FTC exposures relative to
      currently approved individual agents and was thus selected for subsequent
      evaluation.

PMID- 20683272
TI  - Effects of reflected CO2 laser energy on operative field materials: risks to
      patients and operating room personnel.
AB  - This study investigates the effects of specularly and diffusely reflected CO2
      laser energy on operative field materials. The CO2 laser was reflected off the
      sandblasted and polished surfaces of an eyelid plate and a wet cotton gauze pad.
      The laser was aimed at a surgical glove, operative gown, laser safety goggles,
      and endotracheal tube, each positioned 5 cm, 10 cm, and 15 cm from the plate.
      Primary outcomes were time to initial effect and description of result. There was
      no reflection off wet gauze and no effect on the gauze itself. When reflected off
      sandblasted and polished surfaces, the laser created a hole in the glove and a
      flame in the surgical gown. When targeting safety goggles and an endotracheal
      tube, the laser created a surface divot at short distances and surface
      irregularity at 15 cm. While the CO2 laser is an excellent surgical instrument,
      reflected laser energy can affect operative field materials.

PMID- 20683273
TI  - Demonstration of bacterial biofilms in culture-negative silicone stent and jones
      tube.
AB  - PURPOSE: To demonstrate the presence of bacterial biofilms on a
      dacryocystorhinostomy silicone stent and a Jones tube. METHODS: One
      dacryocystorhinostomy silicone stent and one Jones tube were removed from 2
      patients who presented with an infection of their respective nasolacrimal system.
      Cultures were obtained, and the implants were processed for scanning electron
      microscopy and confocal laser scanning microscopy, advanced microscopic methods
      that are applicable for detection of uncultivable biofilm organisms. RESULTS:
      Routine bacterial cultures revealed no growth, but bacterial biofilms on outer
      and inner surfaces of both implants were confirmed by advanced microscopic
      techniques. CONCLUSIONS: To the authors' knowledge, this is the first article
      that documents the presence of biofilms on a Crawford stent or a Jones tube on
      patients who presented with infections involving the nasolacrimal system.
      Although initial cultures revealed absence of any bacterial growth, confocal
      laser scanning microscopy and scanning electron microscopy documented bacterial
      colonization. Clinicians should consider the role of biofilms and the limitation
      of our standard culturing techniques while treating patients with device- or
      implant-related infections.

PMID- 20683274
TI  - Can methylphenidate objectively provide relief in patients with uncontrolled
      blepharospasm? A pilot study using surface electromyography.
AB  - PURPOSE: To determine whether there is an objective benefit to prescribing
      Ritalin for patients with uncontrolled blepharospasm exists. METHODS: Seven
      subjects with benign essential blepharospasm, who were being treated with
      botulinum toxin injections and Ritalin LA, were recruited for this pilot study.
      Patients were asked to participate during the period of time when symptoms were
      beginning to return. Subjects underwent video and surface electromyography (sEMG)
      monitoring before and 2 hours after the administration of Ritalin. Mean sEMG
      potential for each eye was compared before and after the administration of
      Ritalin. Subjects also rated their disability based on a previously developed and
      reproducible blepharospasm functional disability scale. Functional Disability
      Scores were compared, and post-Ritalin treatment benefit was determined. RESULTS:
      The mean voltage of the sEMG was lower in 13 of 14 eyes after the administration
      of Ritalin. For the right eye, the voltage decreased by 50% (106.4 +/- 13.6 mV to
      52.7 +/- 7.1 mV, p = 0.015), and for the left eye, by 31% (81.9 +/- 9.7 mV to
      56.6 +/- 6.1 mV, p = 0.031). The Functional Disability Scores were also lower
      after the administration of Ritalin than before (p = 0.016). CONCLUSIONS: A
      significant decrease in mean voltage after the administration of Ritalin was
      found in this preselected group of patients. Subjective improvement with
      decreased disability and increased functional benefit was also found in all
      subjects. Based on the results of this study, a randomized, controlled study
      comparing Ritalin versus placebo is needed to determine whether Ritalin should be
      routinely prescribed for benign essential blepharospasm during the symptomatic
      window period.

PMID- 20683275
TI  - Enhanced enlargement of silicone ocular prostheses achieved by silicone gel (MED
      361).
AB  - Recently, silicone prostheses have been used instead of acrylic ocular
      prostheses. The authors sought to assess the ability of silicone gel to
      facilitate the growth of an ocular silicone prosthesis and to determine the best
      application modality to achieve maximal possible growth. Two ocular prostheses
      with similar baseline dimensions and contour were used for comparison of growth
      environment. One prosthesis was placed in an eyelid mold, while the other was
      placed in an open Petri dish. Silicone gel drops (MED-361; NuSil Technology,
      Carpinteria, CA, USA) were administered 3 times daily to both prostheses. Over
      the course of 41 days, an equal amount of enlargement occurred in all dimensions
      in both prostheses. Enlargement of a silicone prosthesis can be achieved by
      various modes of application of topical silicone gel.

PMID- 20683276
TI  - Ocular bacillary angiomatosis in an immunocompromised man.
AB  - An immunocompromised man presented with an inflammatory eyelid lesion. Biopsy was
      performed; histopathology and special staining confirmed a diagnosis of bacillary
      angiomatosis. The man was treated with oral erythromycin, and the lesion
      resolved. The etiologic agents of bacillary angiomatosis are Bartonella henselae
      and Bartonella quintana, Gram-negative coccobacilli. The organisms stain
      positively with the Warthin-Starry silver stain. Lesions can be cutaneous or
      visceral and have been commonly described in immunocompromised patients.
      Histopathologic examination of lesions reveals angiogenesis and cellular
      proliferation. Bacillary angiomatosis can be treated with oral antibiotics.

PMID- 20683277
TI  - Orbital abscess caused by viridans Streptococcus.

PMID- 20683278
TI  - Orbital decompression in the treatment of proptosis due to high axial myopia.
AB  - PURPOSE: To report the results of orbital decompression surgery for proptosis due
      to high axial myopia. METHODS: The clinical records and imaging of 8 consecutive
      patients with high axial myopia who underwent orbital decompression surgery to
      treat disfiguring proptosis were reviewed. Data collected included preoperative
      and postoperative best-corrected visual acuity, Hertel exophthalmometry, ocular
      motility examination findings, and surgical complications. RESULTS: Eight
      patients (6 women) with a median presenting age of 53 years (range, 41-78 years)
      underwent unilateral bony orbital decompression surgery to treat proptosis due to
      unilateral or asymmetric high axial myopia. Indications for surgery were
      disfigurement in all patients and exposure keratopathy in 4 patients. All
      patients had more than 12 diopters of myopia on the operated side and axial
      lengths between 27.5 and 34.7 mm. Preoperative visual acuity was reduced in all
      patients owing to amblyopia and/or myopic retinal degeneration. In addition, 2
      patients had mild symmetrical thyroid-related orbitopathy. After orbital
      decompression surgery, Hertel exophthalmometry measurements on the operated side
      were within 2 mm of the other side in all patients. The mean reduction in
      proptosis was 2.3 mm after deep lateral orbital wall decompression (3 patients),
      4.3 mm after medial and lateral wall decompression (3 patients), and 5 mm after 3
      wall decompression (2 patients). Five patients had a hypotropia on the operated
      side, and inferior rectus recession was performed in 4. Two patients underwent
      additional eyelid procedures. No surgical complications were observed.
      CONCLUSIONS: Orbital decompression to reduce proptosis in patients with
      unilateral or asymmetric high axial myopia can improve cosmesis with low
      morbidity.

PMID- 20683279
TI  - Evaluation of homeopathic Arnica montana for ecchymosis after upper
      blepharoplasty: a placebo-controlled, randomized, double-blind study.
AB  - PURPOSE: Ecchymosis is commonly encountered after upper eyelid blepharoplasty.
      The use of homeopathic preparations of Arnica montana, a flowering herb, has been
      advocated by physicians, patients, and manufacturers for reduction of
      postsurgical ecchymosis. The authors evaluate its efficacy after upper eyelid
      blepharoplasty. METHODS: A prospective, placebo-controlled, double-blind study
      was performed in which patients were randomly assigned to the administration of
      homeopathic A. montana or placebo concurrent with unilateral upper eyelid
      blepharoplasty followed by contralateral treatment at least 1 month later.
      Ecchymosis was evaluated at days 3 and 7 by rank order of severity and
      measurement of surface area of observable ecchymosis. RESULTS: There was no
      statistically significant difference in area of ecchymosis or rank order of
      ecchymosis severity for days 3 and 7 after treatment with A. montana versus
      placebo. Additionally, there was no difference in ease of recovery per patient
      report, and there was no difference in the rate of ecchymosis resolution.
      CONCLUSIONS: The authors find no evidence that homeopathic A. montana, as used in
      this study, is beneficial in the reduction or the resolution of ecchymosis after
      upper eyelid blepharoplasty.

PMID- 20683280
TI  - A modified Jones test: lacrimal scintigram correlation.
AB  - PURPOSE: To determine the correlation between lacrimal scintigraphy and a
      modified Jones primary dye drainage test combined with the fluorescein dye
      disappearance test (DDT) and Jones secondary dye test, in diagnosing the cause of
      epiphora. METHODS: A prospective, consecutive clinical trial was conducted. All
      patients presenting with epiphora were considered, but those with trichiasis,
      corneal irritation, lower eyelid ectropion, Bell palsy, or previous lacrimal
      surgery were excluded. A cohort of 39 patients (65 eyes) underwent the
      fluorescein DDT and the senior author's (R.B.) modified Jones primary dye
      drainage test (Jones dye test 1 [JDT1]). For this test, an entire fluorescein 2%
      Minim dose was instilled in the 2 eyes, and the patient was then asked to gently
      blow each nostril separately in a white tissue; the degree of fluorescein
      staining was noted. If there was no fluorescein staining of the tissue (negative
      JDT1), a traditional Jones secondary dye test (Jones dye test 2) was also
      performed. All patients except for those testing strongly positive on modified
      testing or with negative DDT and JDT1 and nil drainage from the nose in Jones dye
      test 2, indicating anatomical obstruction, were referred for lacrimal
      scintigraphy. RESULTS: In total, 59 of 65 eyes (91%) showed a positive
      correlation between the diagnosis arrived at after dye testing using the modified
      primary dye test and diagnosis on lacrimal scintigraphy. The interrater
      reliability for the raters was found to be kappa = 0.770 and 95% confidence
      interval = 0.594-0.945. The strength of agreement is considered to be "good."
      CONCLUSIONS: The authors found that in the presence of patent lacrimal drainage
      system dysfunction, modified Jones primary dye test, combined with the
      fluorescein DDT and Jones secondary dye test, correlated strongly with lacrimal
      scintigraphy.

PMID- 20683281
TI  - Utility of leflunomide in the treatment of complex cytomegalovirus syndromes.
AB  - BACKGROUND: Cytomegalovirus (CMV) viremia that is resistant or refractory to the
      standard antiviral therapy still constitutes a major threat to high-risk
      transplant recipients. In addition, multiple CMV recurrences may lead to
      neutropenia because of repeated courses of therapy with ganciclovir derivatives.
      Leflunomide, a drug for rheumatoid arthritis, has been reported to have anti-CMV
      activity. This study reports on its use in 17 transplant recipients with complex
      CMV syndromes who had failed or were intolerant to other therapies. METHODS:
      Single-center, retrospective study. Clinical data were extracted from the
      electronic medical record. CMV DNA viral loads were performed by quantitative
      hybrid capture assay. RESULTS: Leflunomide was initiated after a median of three
      episodes of CMV viremia, with a mean peak viral load of 245,826 copies/mL.
      Initial clearance of CMV viremia was observed in 14 of 17 patients (82%), and 9
      of 17 (53%) patients achieved a long-term suppression of CMV recurrences. Higher
      peak viral load and higher viral load at the start of leflunomide therapy were
      associated with failure to suppress viremia. The duration of leflunomide therapy
      ranged from 1 to 24 months (median 3.5 months, interquartile range 2.6-7 months),
      and the mean time to an undetectable CMV-DNA was 1.9 months. Adverse effects
      included diarrhea (35%), anemia (18%), and increased liver function tests (12%).
      CONCLUSIONS: Leflunomide, alone or in combination, has potential utility in
      treatment of complex CMV syndromes and in long-term suppression of viremia. The
      optimal duration of therapy and the balance of risks and benefits are not yet
      known.

PMID- 20683282
TI  - A license to learn.

PMID- 20683283
TI  - Clinical evaluation of freeze-dried cancellous block allografts for ridge
      augmentation and implant placement in the maxilla.
AB  - A number of grafting materials have been used in vertical and horizontal ridge
      augmentation to enable implant placement in optimal positions. Autogenous block
      grafts from intraoral or extraoral sites have been used with positive results.
      Allograft blocks with cortical bone are also used for ridge augmentation. In this
      case series, cancellous allograft blocks were used for horizontal augmentation of
      the maxilla. The observed increase in ridge width allowed subsequent implant
      placement after a 5-month healing period. Four months after placement, the
      implants were uncovered and restored. The results suggest that cancellous block
      allografts may be a viable alternative to autogenous block grafts or cortical
      allograft blocks in treatment of deficient maxillary alveolar ridges to allow
      subsequent implant placement in optimal position in the maxilla.

PMID- 20683284
TI  - Bone grafting by means of a tunnel dissection: predictable results using stem
      cells and matrix.
AB  - Bone marrow aspirate has been shown to add stem cells, growth factors, and
      cytokines to bone graft matrices used in bone augmentation sites. The combination
      of bone marrow aspirate and resorbable scaffold material has a significant
      osteogenic capability that exceeds that of autogenous bone grafts. This article
      describes a subperiosteal tunneling technique for applying such grafts to
      defective sites. Treatment of 2 patients for whom the technique was used to graft
      6 deficient sites is described. Histological results and histomorphometric
      analysis of bone core samples taken from 4 of the 6 grafting sites are also
      reported. Analysis of the 4 bone cores taken between 4 and 6 months showed a
      range of 34% to 45% of new bone.

PMID- 20683285
TI  - Dental imaging in implant treatment planning.
AB  - OBJECTIVES: Proper implant treatment planning remains the first priority for
      implant success. Dental imaging is an important tool to accomplish this task.
      Traditional radiographs provide adequate information about proposed implant
      sites; however, limited film size, image distortion, magnification, and a 2-D
      view restrict their use in some cases. The purpose of this study is to provide an
      update about recent advancements in implant imaging to facilitate ideal implant
      treatment planning. SEARCH STRATEGY: A literature search was conducted using
      MEDLINE to identify studies related to this topic using the keywords of implant
      imaging, computed tomography (CT), cone beam CT (CBCT), and digital implant
      planning. RESULTS: Medical CT scan produce 3-dimensional replicas of anatomical
      areas with high resolution and accuracy. Although this type of imaging was
      introduced almost 20 years ago for implant planning, until recently it is widely
      used in most of the advanced procedures. CBCT is an advanced version of this
      technique. The advantages of CBCT are its specific design for the maxillofacial
      region, a reduced radiation exposure, cheaper, and excellent quality of images.
      Today, many companies are developing these cutting-edge machines and making it
      possible for dentists to use in their practices. CONCLUSIONS: Coupled with
      converting software programs, CT/CBCT images may assist in selecting implant
      dimensions and predicting treatment outcomes. Understanding the up-to-date
      development of imaging aids could potentiate our ability in planning implant
      therapy.

PMID- 20683286
TI  - Piezoelectric-assisted osteotome-mediated sinus floor elevation: an innovative
      approach.
AB  - Sinus floor elevation can be done by lateral maxillary approach or crestal
      approach by osteotome techniques as a function of residual bone height. The
      osteotome technique has been developed for minor sinus floor elevation. This is a
      method with relatively high predictability but is technically demanding. During
      the past decade, different osteotome-mediated sinus floor elevation techniques
      have been developed to augment the sinus for predictable implant placement. All
      these methods aim to access a better, predictable sinus augmentation with low
      morbidity. Some of these techniques require special equipment or materials,
      complicated procedure, and a long learning curve. This article describes an
      innovative approach to sinus augmentation, namely, piezoelectric-assisted
      osteotome-mediated sinus floor elevation. This method uses a newly designed
      piezoelectric tip, which can perform sinus floor osteotomy in a simple and
      atraumatic way. This approach has the greatest advantages of good tactile sense
      in osteotomy, least perforation, patient comfort with the least and lightest
      malleting, and shortened surgery. This method may be the most favorable osteotome
      technique in the future.

PMID- 20683287
TI  - Healing of extraction socket grafted with deproteinized bovine bone and acellular
      dermal matrix: histomorphometric evaluation.
AB  - Various materials have been used to prevent or minimize ridge collapse after
      tooth extraction in an attempt to improve implant placement. The bone graft
      material used for filling bone defects after tooth extraction is a controversial
      topic. This is especially so if there is an apical lesion at the site of the
      natural tooth. A patient who presented with a retained root and apical lesion was
      treated with bone grafting as a staged implant placement. Histological analysis
      of a biopsy done 6 months after grafting revealed good healing with mature bone.
      Histomorphometric evaluation showed 39.4% bony tissue. The implant that was
      installed was mainly in the regenerated area and the prosthesis was well in
      function up to 6 months.

PMID- 20683288
TI  - Ridge bone maintenance in human after extraction.
AB  - PURPOSE: The aim of this study was to evaluate, clinically and histologically,
      the tissues formed in human alveolar sockets filled with bovine morphogenetic
      protein/bovine organic matrix (BOM) and absorbable membrane (AM) immediately
      after extraction. MATERIALS: Forty-six human alveolar sockets, exhibiting buccal
      bone defects were selected for this study. Group 1 received no biomaterial to
      serve as control. Sockets from group 2 were filled with bovine bone morphogenetic
      protein (bBMP) associated with bOM. The association of bBMP/bOM/AM filled the
      alveolar defects from group 3. AM was placed over the defects from group 4.
      Clinical evaluation analyzed ridge width before biomaterial filling and 4 months
      after filling. Fifteen specimens were collected from groups 2, 3, and 4 for
      histologic analyses. RESULTS: Clinical results showed no significant augmentation
      on the control group (-0.16 +/- 0.28 mm). All test sites, groups 2, 3, and 4,
      showed relevant ridge width augmentation (3.0 +/- 0.5 mm, 2.4 +/- 0.3 mm, and 2.9
      +/- 0.6 mm, respectively) and no resorption. Histologically, all experimental
      alveolar sockets showed active bone formation with osteoid, osteoblasts, and cell
      differentiation. CONCLUSION: On the basis of this study, we concluded that
      bBMP/bOM with or without AM could preserve the ridge showing viable bone
      formation for future implant placement.

PMID- 20683289
TI  - One-year clinical outcome of dental implants placed in patients with type 2
      diabetes mellitus: a case series.
AB  - PURPOSE: Diabetes mellitus is a prevalent medical disorder. It is often
      accompanied with systemic adverse sequelae, such as wound healing alterations,
      which may affect osseointegration of dental implants. The use of dental implants
      in patients with diabetes mellitus remains controversial because altered bone
      healing around implants has been reported. The purpose of this study was to
      present 1-year clinical outcomes of 23 implants placed in 10 patients with well-,
      or moderately well, controlled type 2 diabetes mellitus. MATERIALS: All implants
      were uneventfully placed in the mandible or maxilla. Three different types of
      definitive implant-supported prostheses, cement- or screw-retained fixed dental
      prostheses, and overdentures were delivered to the patients. RESULTS: At 1-year
      follow-up recall, no implants were lost, and 0.3 +/- 0.2 mm marginal bone loss
      was noted. No periapical radiolucencies, no bleeding on probing, or pathologic
      probing depth were recorded at these recalls. CONCLUSION: This clinical report
      supports the use of dental implants in patients with well-, or moderately well,
      controlled type 2 diabetes mellitus as a dental treatment modality. No evidence
      of diminished clinical success or significant complication related to implant
      treatment was found for this patient population.

PMID- 20683290
TI  - Clinical and histologic outcomes after the use of a novel allograft for maxillary
      sinus augmentation: a case series.
AB  - PURPOSE: To document the clinical and histologic outcomes of sinus augmentation
      using a novel allogenic bone substitute as a sole grafting material. MATERIALS:
      Patients in need of sinus augmentation before implant placement were recruited
      for this study. Sinus augmentation procedures were performed following a lateral
      approach, using a freeze-dried allograft as the only grafting material. Patients
      were followed up postoperatively for 6 months. Plaque score, wound healing, and
      patient discomfort were recorded at each follow-up visit. Implants were placed
      between 6 and 7 months after sinus augmentation and restored 6 months later. Bone
      core biopsy specimens were harvested at the time of implant placement and
      processed for histologic and histomorphometrical analysis. Vital bone, remaining
      allograft (RA) particles, and nonmineralized tissue percentages were assessed on
      each sample. Results were expressed as mean percentages with SD. RESULTS: Of the
      23 sinus patients, 20 patients underwent sinus augmentation surgery. All patients
      had satisfactory postoperative healing in the absence of complications. A total
      of 39 implants were placed. One implant failed and was replaced 3 months later.
      Histologic analysis revealed the presence of well-organized lamellar bone, in
      direct contact with RA particles. Mean vital bone was 23.02 +/- 19.11%, mean RA
      was 22.25 +/- 20.30%, and average nonmineralized tissue was 54.73 +/- 13.51%.
      CONCLUSION: Clinical and histologic findings support the suitability of an
      allograft consisting of a combination of cortical and cancellous chips for sinus
      augmentation procedures.

PMID- 20683291
TI  - Retrospective study of bone grafting procedures before implant placement.
AB  - AIM: The aim of this retrospective study was to evaluate morbidity and possible
      complications in augmentation procedures before implant placement. METHODS:
      Records from 93 consecutive patients with indication for autogenous bone grafting
      before implant placement, treated at Department of Oral and Maxillofacial Surgery
      and Implantology of Uberlandia Federal University, in a 7-year period (July 2000
      until July 2007), were reviewed. The need for bone grafting was defined by the
      impossibility of installing implants of adequate length or diameter to fulfill
      prosthetic requirements or for aesthetic reasons. RESULTS: A total of 136 bone
      grafting procedures were performed. The mandibular external oblique line and
      ascending ramus were the most frequently used donor areas (59.64%) and block
      grafts (67.64%) were the most frequently used type of graft, frequently from the
      mandibular external oblique line/ascending ramus (52.18%). Platelet-rich plasma
      was used in 20.1% of all procedures, usually associated with particulate bone
      grafts. Maxillary procedures represented the majority of surgeries (75%), but
      with fewer complications compared with the mandible. Sinus mucosa perforation was
      the most frequent complication in maxillary procedures, whereas graft exposure
      was the most common complication in mandible. CONCLUSIONS: Alveolar
      reconstruction using autogenous bone followed by implant placement is a reliable
      treatment for patients with insufficient bone. Complications and morbidity were
      frequently observed. However, in only 6.6% of all procedures, the final
      rehabilitation with dental implants was not possible.

PMID- 20683292
TI  - A 10-year longitudinal study of 160 implants simultaneously installed in severely
      atrophic posterior maxillas grafted with autogenous bone and a synthetic
      bioactive resorbable graft.
AB  - PURPOSE: This study intended to evaluate by clinical and imaging parameters the
      long-term predictability of osseointegrated implants inserted with specific
      simultaneous sinus lift approach in very atrophic posterior maxillas using a
      synthetic bioactive resorbable graft and autogenous bone graft. PATIENTS AND
      METHODS: A total of 160 implants were inserted in 57 maxillary sinus of 45
      consecutive patients (16 men, 29 women) presenting 4 mm or less of residual
      subsinus bone in a simultaneous approach with the sinus lift procedure. All
      patients were surgically treated by the same surgeon and received the same
      modified technical and biomaterial protocol with a composite graft made of
      autogenous bone and a synthetic bioactive resorbable graft (OsteoGen, Impladent,
      Holliswood, NY) in a 1:1 rate. Among the inclusions criteria was a minimum
      loading time of 6 months to assure bone response activity. All patients were
      followed up for a mean period of 61.7 months (range, 20-132 months) with
      clinical, digital pictures, and radiographic aspects. Specific cases were
      followed up with computerized tomography scans (27.2%) with the consent form
      signed. RESULTS: Survival and success rates were 98.05% and 94.85%, respectively.
      CONCLUSION: Advanced posterior maxillary resorption with extensive expanded sinus
      (SA-4 condition) can be safely treated by a simultaneous sinus lift approach and
      implant insertion using the technical protocol and biomaterials studied.

PMID- 20683293
TI  - Prevention of delay in the patient discharge process: an emphasis on nurses'
      role.
AB  - Planning for a patient's postdischarge needs care does not begin on the day when
      decision is made to release the patient from the hospital. It is generally
      accepted that discharge planning should start before admission (for a planned
      admission) or at the time of admission (for an unplanned admission). A
      combination of individual factors, most notably age, medical factors such as
      presence of multiple pathology, and organizational factors such as lack of
      alternative forms of care facilities put patients at risk of delayed discharge.
      Moreover, lack of nurses' participation also contributes toward the delaying of
      discharge. In this article, the author provides strategies to improve nurses'
      participation in discharge planning and discusses the importance of involving
      patients and their caretakers in decision making.

PMID- 20683295
TI  - How to teach human caring: nurse educator role in transformational learning for a
      large healthcare system.
AB  - Nurse educators assisted the director of professional nursing practice in a large
      healthcare system to implement a human caring program across 108 nursing units.
      These educators used transformational learning principles to reunite bedside
      nurses with the art of caring. Implementation included core content in a 30
      minute training session, large-scale leadership conferences, and consistent
      educator support. Affective growth occurred for both clinicians and educators.
      The authors provide practical ideas, content, and tools to teach human caring.

PMID- 20683294
TI  - Providing orientation programs to new graduate nurses: points to consider.
AB  - Staff educators know the importance of orientation for nurses and strive to
      develop effective orientation programs in both general and specialized clinical
      areas. However, little is written about what constitutes a 'good' orientation,
      especially for the new graduate. This article provides a summary of the current
      literature on nursing orientation and provides an overview of various timelines
      utilized in different settings, frameworks to guide the development and
      implementation of an orientation and a brief description of the mentor and
      preceptor roles. Implications for staff educators, nurse managers, and the
      organization are described.

PMID- 20683296
TI  - The association of health care journalists conference.

PMID- 20683297
TI  - A retention strategy for newly graduated nurses: an integrative review of
      orientation programs.
AB  - To address nurse recruitment and retention issues, hospitals have increased the
      number of newly graduated nurses in their hiring pools and have simultaneously
      established orientation programs for those nurses. Structured orientation
      programs facilitate newly graduated nurse transition from novice to advanced
      beginner. The outcome of these programs is twofold: First, they promote the
      confidence and competency level of new nurses in providing patient care, and
      second, they increase nurse retention. This literature review presents the most
      useful interventions used in the programs that reported positive affects on new
      nurses.

PMID- 20683298
TI  - A retention strategy for newly graduated nurses: an integrative review of
      orientation programs.

PMID- 20683299
TI  - Development of an educational module on provider self-care.
AB  - Intensive care providers who care for traumatized populations often face multiple
      traumas for extended periods and are vulnerable to developing lasting symptoms of
      compassion fatigue and secondary traumatization. Symptoms are often not
      recognizable until compassion fatigue or secondary traumatization negatively
      affects the providers' ability to care for their patients. More attention needs
      to be given to the care of the provider to ensure high-quality patient care,
      decrease turnover in the profession, and increase productivity. This article
      provides a framework for the development of an educational module for healthcare
      providers' self-care. This educational module created the opportunity to share
      with providers (a) how to explore their own professional experience; (b) how to
      recognize the different symptoms of compassion fatigue, primary traumatization,
      and secondary traumatization; (c) factors related to grief reactions; and (d)
      personal and professional strategies to decrease compassion fatigue and secondary
      traumatization.

PMID- 20683300
TI  - Web-based learning for continuing nursing education of emergency unit staff.
AB  - The authors describe a Web-based continuing education course focusing on patient
      counseling in an emergency department. Course materials were developed based on
      data collected from the department's patients and their family members and on
      earlier findings on counseling. Web-based education is an appropriate method for
      continuing education in a specific hospital department. This puts special demands
      for nurse managers in arranging, designing, and implementing the education
      together with educators.

PMID- 20683301
TI  - Impact of incorporating a patient-centered care model.
AB  - The author describes a program that educates nurses to use the Relationship &
      Results Oriented Healthcare concepts to increase patient and staff satisfaction
      and decrease nurse turnover.

PMID- 20683302
TI  - Self-efficacy-based training for research literature appraisal: a competency for
      evidence-based practice.
AB  - Evidence-based practice requires nurses to integrate research findings into
      patient care. The lack of skill and confidence in effective literature appraisal
      remains a barrier for many nurses. The author describes a self-efficacy-based
      pilot project designed to enhance nurses' skill and confidence, thus increasing
      their ability and willingness to critically evaluate research findings. After the
      intervention, nurses were better prepared to critically appraise the literature
      and, through enhanced readiness, were more inclined to make evidence-based
      practice a clinical reality. This approach may be beneficial to staff development
      educators to develop and enhance an evidence-based practice culture.

PMID- 20683303
TI  - A preceptor cafe: serving up universal values for preceptors.
AB  - How do you affirm meaning and articulate values that will serve as the bedrock of
      a preceptor program? The Medical Specialty Preceptor Committee in a large
      hospital system planned a series of preceptor forums for 88 medical specialty
      preceptors. The goals were to renew commitment, refresh vision, and develop
      strategies for successfully orienting new hires. This study began by examining
      the work of JoEllen Koerner in her book Healing Presence: The Essence of Nursing.
      The universal values in her model involve acknowledging and addressing three
      basic levels: safety needs, relationship needs, and self-esteem needs,
      encompassing the individual's connection to the external world. The middle level
      is labeled transformation and goes beyond the first three levels to how the
      individual expresses the authentic self within the working world. The higher
      levels involve intuition, intention, and self-actualization and focus on the
      inner world of the individual. The needs of orientees could be met in all of
      these dimensions, based on existing structure and process in the organization.
      Relationship-based care as our nursing model guides holistic care. Our rich
      institutional heritage promotes values-based teamwork. Our goal was to articulate
      these values and hold discussions among preceptors about how these values could
      be expressed and developed in orientees. These cafe conversations were held as
      spring forum sessions. This article highlights essential ideas at the core of
      this preceptor activity.

PMID- 20683304
TI  - Nursing professional development: stories, tips, and techniques.

PMID- 20683305
TI  - Copyright: who's right and who has rights.

PMID- 20683306
TI  - Share and share alike: exchanging innovations and best practices on the web.

PMID- 20683308
TI  - Interictal epileptiform discharges and epilepsy severity.

PMID- 20683310
TI  - Optometric researchers honored at ARVO 2010.

PMID- 20683311
TI  - Pathogenesis of contact lens-associated microbial keratitis.

PMID- 20683314
TI  - No evidence of increased sexual risk behaviour after initiating antiretroviral
      therapy among people who inject drugs.
AB  - OBJECTIVE: Although antiretroviral therapy (ART) dramatically reduces viral load
      and improves survival among HIV-infected injection drug users (IDUs), several
      short-term studies have raised concerns that ART initiation may result in
      increases in sexual risk behaviour among IDUs. DESIGN: We used data from a long
      running cohort of HIV-positive IDUs to examine whether ART initiation was
      associated with increases in several measures of sexual risk behaviour. The date
      of ART initiation was determined through a validated linkage to a centralized ART
      dispensation pharmacy. METHODS: We used generalized linear mixed-effects
      modelling to examine whether sexual activity, unprotected intercourse, and
      multiple sexual partnerships were more likely in the 12-month period following
      ART initiation. RESULTS: Among 457 individuals who were ART naive at baseline,
      the median age was 34 [interquartile range (IQR) 28-41] and 202 (44.2%) were
      women. Between May 1996 and April 2008, 260 (56.7%) participants initiated ART.
      In multivariate analyses, ART initiation was not associated with sexual activity
      [adjusted odds ratio (AOR) = 0.87, 95% confidence interval (CI) 0.60-1.25],
      unprotected intercourse (AOR = 0.82, 95% CI 0.51-1.31), or multiple sexual
      partnerships (AOR = 0.93, 95% CI 0.61-1.40). CONCLUSION: In this study of HIV
      positive IDUs, we failed to detect an increase in sexual risk behaviour during
      the period following ART initiation. In light of this evidence, and given the
      known positive effect of ART on survival and its potential role in reducing HIV
      transmission, concerns regarding potential increases in sexual risk-taking should
      not undermine the delivery of ART to IDUs.

PMID- 20683315
TI  - An appraisal of indicators used to monitor the treated population in
      antiretroviral programmes in low-income countries.
AB  - Monitoring the progress of HIV programmes is vital, as services are scaled up to
      include increasing numbers in need of care. Globally, the presence of multiple
      donors at all levels of HIV care has produced vast monitoring systems. Within HIV
      treatment programmes in low and middle-income countries, directly assessing long
      term outcomes such as survival is problematic, so indicators are used to monitor
      the progress of the treated population. However, the internal, external,
      construct validity and predictive value of current indicators have never been
      evaluated. Although the burden on facility staff compiling routine monitoring
      reports is vast, there is uncertainty as to which indicators best monitor patient
      progress. This burden will grow as increasing numbers of life-cohorts are created
      for monitoring purposes leading to data inaccuracies and compromising the
      internal validity of reported indicators. Furthermore, a number of fundamental
      indicators, including survival and retention, may not capture the construct they
      intend to measure, compromising the ability of programme managers to obtain
      reliable estimates regarding the welfare of their population in care. It is not
      known which indicators can predict the longer-term outcome of the patient
      population, and as such, can enable managers to respond to predictors of failure
      early. An evaluation of current indicators is urgently needed to ensure that
      reported facility-level data accurately reflect the welfare of the treated
      population and comparisons of programme performance are meaningful.

PMID- 20683316
TI  - Prospective study of bone mineral density changes in aging men with or at risk
      for HIV infection.
AB  - OBJECTIVE: To investigate rates and predictors of change in bone mineral density
      (BMD) in a cohort of aging men with or at risk for HIV infection. DESIGN: A
      prospective cohort study among 230 HIV-infected and 159 HIV-uninfected men aged
      at least 49 years. METHODS: Longitudinal analyses of annual change in BMD at the
      femoral neck, total hip, and lumbar spine. RESULTS: At baseline, 46% of men had
      normal BMD, 42% had osteopenia, and 12% had osteoporosis. Of those men with
      normal BMD, 14% progressed to osteopenia and 86% continued to have normal BMD. Of
      the men initially with osteopenia, 12% progressed to osteoporosis and 83%
      continued to have osteopenia. Osteopenia incidence per 100 person-years at risk
      was 2.6 for HIV-uninfected men and 7.2 for HIV-infected men; osteoporosis
      incidence was 2.2 per 100 person-years at risk among men with osteopenia,
      regardless of HIV status. In multivariable analysis of annual change in BMD at
      the femoral neck, we found a significant interaction between heroin use and AIDS
      diagnosis, such that the greatest bone loss occurred with both AIDS and heroin
      use (adjusted predicted mean annual bone loss 0.0196 g/cm). Hepatitis C virus
      seropositivity was also associated with femoral neck bone loss (P = 0.04). The
      interaction between AIDS and heroin use also was associated with bone loss at the
      total hip, as was current methadone use (P < 0.01). CONCLUSION: We found an
      association of heroin use and AIDS with BMD change, suggesting that heroin users
      with AIDS may be at particular risk for bone loss.

PMID- 20683317
TI  - Flexible use of CCR5 in the absence of CXCR4 use explains the immune deficiency
      in HIV-1 infected children.
AB  - DESIGN: CCR5-using HIV-1 (R5 viruses) are usually isolated during acute infection
      from both adults and children. We have recently demonstrated that R5 viruses with
      a flexible use of CCR5 (called R5broad) can be detected in children close to
      birth and are predictive of a fast immunological failure. The aim of the present
      work was to investigate viral phenotype variation during disease progression in
      HIV-1 infected children, six slow and eight fast progressors. METHODS: A total of
      74 viral isolates obtained sequentially from 14 HIV-1 infected children were
      tested for their ability to infect U87.CD4 cells expressing a set of six
      different CCR5/CXCR4 chimeric receptors or wild-type coreceptors. The sensitivity
      of 35 R5 viruses to inhibition with the CC-chemokine RANTES (regulated upon
      activation, normal T-cell expressed and secreted) was evaluated in a peripheral
      blood mononuclear cells based assay. RESULTS: Viral evolution to R5broad or to
      R5X4 phenotype occurred with one exception, in all children, although at a
      different time point according to rate of disease progression. Immune deficiency
      in the children was significantly associated with the appearance of R5broad
      phenotype or R5X4 viruses. Analysis of the sensitivity to inhibition by RANTES
      revealed a significant correlation between the R5broad phenotype and an augmented
      resistance to this CC-chemokine. CONCLUSION: We demonstrate that the viral
      evolution to a more flexible CCR5-use is sufficient to explain the immunological
      failure in the absence of CXCR4 usage. These results warrant detailed analysis of
      the R5 phenotype in forthcoming clinical studies introducing CCR5 inhibitors for
      the treatment of pediatric HIV-1 infection.

PMID- 20683318
TI  - Temporal changes in programme outcomes among adult patients initiating
      antiretroviral therapy across South Africa, 2002-2007.
AB  - OBJECTIVE: Little is known about the temporal impact of the rapid scale-up of
      large antiretroviral therapy (ART) services on programme outcomes. We describe
      patient outcomes [mortality, loss-to-follow-up (LTFU) and retention] over time in
      a network of South African ART cohorts. DESIGN: Cohort analysis utilizing
      routinely collected patient data. METHODS: Analysis included adults initiating
      ART in eight public sector programmes across South Africa, 2002-2007. Follow-up
      was censored at the end of 2008. Kaplan-Meier methods were used to estimate time
      to outcomes, and proportional hazards models to examine independent predictors of
      outcomes. RESULTS: Enrolment (n = 44 177, mean age 35 years; 68% women) increased
      12-fold over 5 years, with 63% of patients enrolled in the past 2 years. Twelve
      month mortality decreased from 9% to 6% over 5 years. Twelve-month LTFU increased
      annually from 1% (2002/2003) to 13% (2006). Cumulative LTFU increased with follow
      up from 14% at 12 months to 29% at 36 months. With each additional year on ART,
      failure to retain participants was increasingly attributable to LTFU compared
      with recorded mortality. At 12 and 36 months, respectively, 80 and 64% of
      patients were retained. CONCLUSION: Numbers on ART have increased rapidly in
      South Africa, but the programme has experienced deteriorating patient retention
      over time, particularly due to apparent LTFU. This may represent true loss to
      care, but may also reflect administrative error and lack of capacity to monitor
      movements in and out of care. New strategies are needed for South Africa and
      other low-income and middle-income countries to improve monitoring of outcomes
      and maximize retention in care with increasing programme size.

PMID- 20683319
TI  - Time course of total HIV-1 DNA and 2-long-terminal repeat circles in patients
      with controlled plasma viremia switching to a raltegravir-containing regimen.
AB  - BACKGROUND: Early integration of HIV proviral DNA into the host cell genome
      prevents viral eradication, despite suppressive HAART. In vitro, integrase
      inhibitors reduce proviral DNA levels and rapidly increase 2-long-terminal repeat
      (LTR) circle levels. We examined the effect of raltegravir on the time course of
      HIV-1 DNA forms in patients with controlled viremia. PATIENTS AND METHODS: The
      EASIER-ANRS 138 randomized trial demonstrated that switching from enfuvirtide to
      raltegravir maintained virological suppression in treatment-experienced patients
      with viral load below 400 copies/ml. We analyzed total HIV-1 DNA and 2-LTR circle
      levels measured at weeks (W)0 and 24 in the first 30 patients enrolled in each
      arm, and at W48 in the raltegravir arm. RESULTS: At W0 the total DNA level was
      3.6 log(10)/10(6) peripheral blood mononuclear cell (PBMC) in both groups, and 2
      LTR circles were detected in six patients (median 89 copies/10(6) PBMC). At W24
      the total DNA level was 3.6 log(10)/10(6) PBMC in both groups, and 2-LTR circles
      were detected in three new patients. At W48 the total HIV DNA level in the
      raltegravir group was 3.5 log(10)/10(6) PBMC, and 2-LTR circles were
      undetectable. No significant change in total HIV DNA occurred between W0 and W24
      in either arm (P = 0.71) and no significant change was observed in the
      raltegravir arm at W48. DISCUSSION: In most patients on effective HAART,
      including regimens containing an integrase inhibitor, the viral reservoir,
      reflected by the HIV-1 DNA load, is stable and nondynamic during the 48 weeks of
      follow-up.

PMID- 20683320
TI  - The importance of tenascin and ubiquitin in estimation of wound age.
AB  - Human wound age determination is of prime importance in forensic sciences.
      Ubiquitin is a small protein required for ATP-dependent, nonlysosomal
      intracellular protein degradation, which eliminates most of the intracellular
      defective proteins. Tenascin is an extracellular matrix glycoprotein. The aim of
      this study was to determine the importance of ubiquitin and tenascin in wound
      age. Ubiquitin and tenascin were immunohistochemically applied on formalin-fixed
      paraffin-embedded tissues of 170 wound biopsies taken from 89 autopsy cases with
      known wound age. Pearson correlation analysis was performed for statistical
      analysis. The mean age was 39.44 years. Tenascin was negative in 123 cases
      (72.4%) in all series, and it was negative in 98.3% in cases with wound age under
      24 hours. It was positive in 91.8% in cases with wound age over 24 hours. Mean
      number of cells which expressed ubiquitin was 10.56%, while it was 4.25% in cases
      with wound age under 24 hours, and it was 26.14% in cases with wound age over 24
      hours. The correlation analysis showed that both tenascin and ubiquitin were
      positively correlated with wound age. But in cases with wound age over 40 days,
      tenascin was found to be negative and ubiquitin was still expressed in
      fibroblasts. We concluded that tenascin and ubiquitin together was useful in
      determining wound age semiquantitatively.

PMID- 20683321
TI  - Sudden death following delayed traumatic diaphragmatic herniation.
AB  - Blunt force trauma to the chest can often result in diaphragmatic tears. These
      tears can go months without being discovered, until a secondary injury or
      circumstance causes an organ to herniate through the diaphragm. Special care
      should be taken at autopsy to determine the mechanism of injury of any tears in
      the diaphragm as this may influence the cause and manner of death. We present a
      case of a 28-year-old man who suffered multiple injuries in a motor vehicle
      collision. Six months later he presented with a left diaphragmatic tear and
      gastric fundal herniation, and died eventually.

PMID- 20683322
TI  - Antithrombin Cambridge II(A384S) mutation frequency and antithrombin activity
      levels in 120 of deep venous thrombosis and 150 of cerebral infarction patients
      in a single center in Southern China.
AB  - Antithrombin Cambridge II(A384S) mutation shows a relatively high frequency in
      western population. Some studies suggest that the mutation is an independent
      genetic risk factor both for deep vein thrombosis (DVT) and for arterial
      thrombosis, but whether the mutation has racial difference or has a general
      significance for thrombophilia remains unclear. In this study we performed an
      analysis of the prevalence of the mutation in Chinese southern population; Also,
      the antithrombin activity levels were evaluated in each investigated individual.
      The studies included 120 patients with DVT, 150 patients with cerebral
      infarction, and 110 controls. The mutation was detected using polymerase chain
      reaction/PvuII restrictive fragment length polymorphism procedures. Antithrombin
      activity assay was done using chromogenic substrate method. The results showed
      that no antithrombin Cambridge II mutation was detected in all three groups (DVT,
      cerebral infarction and controls), the incidence was 0/380. Plasma antithrombin
      activity was 91.37% +/- 16.15% in the DVT patients and 102.68% +/- 13.10% in the
      controls; the antithrombin activity was significantly reduced in the DVT group (P
      < 0.0001). In DVT patients, eight cases were identified as primary antithrombin
      deficiency, accounting for an incidence of 6.7%. No significant difference was
      found for antithrombin activity between cerebral infarction group and controls.
      These results suggest that antithrombin Cambridge II mutation has a racial
      difference, and may not be a valuable risk factor of thrombophilia in Asian
      population, and antithrombin deficiency remains a major genetic risk factor for
      DVT patients in China.

PMID- 20683323
TI  - Anticoagulant and fibrinogenolytic properties of the venom of Polybia
      occidentalis social wasp.
AB  - Previous studies have shown that venoms of social wasps and bees exhibit strong
      anticoagulant activity. The present study describes the anticoagulant and
      fibrinogen-degrading pharmacological properties of the venom of Polybia
      occidentalis social wasp. The results demonstrated that this venom presented
      anticoagulant effect, inhibiting the coagulation at different steps of the
      clotting pathway (intrinsic, extrinsic and common pathway). The venom inhibited
      platelet aggregation and degraded plasma fibrinogen, possibly containing metal
      dependent metalloproteases that specifically cleave the Bbeta-chain of
      fibrinogen. In conclusion, fibrinogenolytic and anticoagulant properties of this
      wasp venom find a potential application in drug development for the treatment of
      thrombotic disorders. For that, further studies should be carried out in order to
      identify and isolate the active compounds responsible for these effects.

PMID- 20683324
TI  - The antifibrinolytic effects of carbon monoxide-releasing molecule-2 are fibrin
      and alpha2-antiplasmin dependent.
AB  - Carbon monoxide derived from a carbon monoxide-releasing molecule
      [tricarbonyldichlororuthenium (II) dimer; CORM-2] has been recently demonstrated
      to diminish tissue-type plasminogen activator (tPA)-mediated fibrinolysis of
      plasma thrombi via enhancement of alpha2-antiplasmin-plasmin interactions. The
      goal of this study was to confirm this mechanism by comparing tPA-mediated
      fibrinolysis with fibrin-independent, alpha2-antiplasmin-resistant streptokinase
      mediated fibrinolysis in CORM-2 exposed plasma. Normal plasma was exposed to 0 or
      100 micromol/l CORM-2, with coagulation activated with tissue factor and
      fibrinolysis initiated with 100 U/ml tPA or 50 U/ml streptokinase. Thrombus
      growth/disintegration kinetics were monitored with thrombelastography until clot
      lysis time occurred. Unlike tPA-lysed clots, streptokinase-exposed thrombi
      demonstrated no significant CORM-2-mediated prolongation of clot growth time or
      clot lysis time. In contrast, streptokinase-mediated lysis did not significantly
      change the CORM-2-mediated percentage increase in the maximum rate of clot growth
      or maximum rate of clot lysis compared with tPA-exposed thrombi. CORM-2 likely
      attenuates fibrinolysis by a fibrin-dependent/alpha2-antiplasmin-dependent
      mechanism. Additional molecular investigation (e.g., mass spectroscopy) is
      planned to further elucidate how CORM-2 modifies fibrinogen/fibrin.

PMID- 20683325
TI  - Relative roles of various efflux pathways in net cholesterol efflux from
      macrophage foam cells in atherosclerotic lesions.
AB  - PURPOSE OF REVIEW: Cholesterol efflux mechanisms are essential for macrophage
      cholesterol homeostasis. HDL, an important cholesterol efflux acceptor, comprises
      a class of heterogeneous particles that induce cholesterol efflux via distinct
      pathways. This review focuses on the understanding of the different cholesterol
      efflux pathways and physiological acceptors involved, and their regulation in
      atherosclerotic lesions. RECENT FINDINGS: The synergistic interactions of ATP
      binding cassette transporters A1 and G1 as well as ATP-binding cassette
      transporter A1 and scavenger receptor class B type I are essential for cellular
      cholesterol efflux and the prevention of macrophage foam cell formation. However,
      the importance of aqueous diffusion should also not be underestimated.
      Significant progress has been made in understanding the mechanisms underlying ATP
      binding cassette A1-mediated cholesterol efflux and regulation of its expression
      and trafficking. Conditions locally in the atherosclerotic lesion, for example,
      lipids, cytokines, oxidative stress, and hypoxia, as well as systemic factors,
      including inflammation and diabetes, critically influence the expression of
      cholesterol transporters on macrophage foam cells. Furthermore, HDL modification
      and remodeling in atherosclerosis, inflammation, and diabetes impairs its
      function as an acceptor for cellular cholesterol. SUMMARY: Recent advances in the
      understanding of the regulation of cholesterol transporters and their acceptors
      in atherosclerotic lesions indicate that HDL-based therapies should aim to
      enhance the activity of cholesterol transporters and improve both the quantity
      and quality of HDL.

PMID- 20683326
TI  - Triglyceride lipases and atherosclerosis.
AB  - PURPOSE OF REVIEW: There are strong epidemiologic connections between plasma
      triglycerides and atherosclerosis. We will consider to what extent this goes back
      to derangements of the lipoprotein lipase (LPL) system. The roles of hepatic
      lipase and endothelial lipase will also be touched upon. RECENT FINDINGS:
      Understanding of LPL action has taken major steps with the discovery of lipase
      maturation factor 1 as a specific endoplasmic reticulum chaperon needed for
      proper folding of the lipases, glycosylphosphatidylinositol-anchored HDL-binding
      protein 1 as an endothelial cell protein needed for transport and binding of LPL
      and some angiopoietin-like proteins that can modulate LPL activity. Studies of
      genetic variants continue to support the important roles of the lipases in
      lipoprotein metabolism and in atherosclerosis. CONCLUSION: There are several ways
      by which derangement of the lipases may contribute to atherogenesis. Lipase
      actions are major determinants of plasma lipoprotein patterns. LPL activity must
      be modulated in relation to the physiological situation (feeding, fasting,
      exercise, etc.). Fatty acids and monoglycerides generated must be efficiently
      removed so that they do not endanger the integrity of the endothelium, cause
      lipotoxic reactions or both. In addition, the lipases may cause binding and
      endocytosis of lipoprotein particles in the artery wall.

PMID- 20683327
TI  - Atherosclerotic lesions in mouse and man: is it the same disease?
AB  - PURPOSE OF REVIEW: Genetically-engineered mice with hyperlipidemia are the most
      widely used atherosclerosis models today, but recent advances in transgenesis
      open the possibility to create new models in alternative species, such as the rat
      and pig. It seems relevant at this point in time to review some of the strengths
      and weaknesses of the mouse. RECENT FINDINGS: The histology of lesion development
      in mouse and man has more similarities than differences, and comparative genetics
      show that many mechanisms of murine and human atherogenesis are shared.
      Unfortunately, the most feared complication of human atherosclerosis, that is,
      plaque rupture and thrombosis, occur extremely rarely in mice. This is a major
      problem. Most patients today are not treated before symptoms ensue, and at this
      late stage of the disease, mechanisms identified during plaque development in the
      mouse may not be very important. SUMMARY: Murine atherosclerosis models are
      highly valuable for identifying atherogenic mechanisms that can be targeted by
      preventive medicine. However, models with thrombotic complications and large
      animal models suitable for interventional procedures and imaging would be more
      supportive for current clinical practice and are highly wanted.

PMID- 20683328
TI  - Interleukin-17: friend or foe in atherosclerosis?
AB  - PURPOSE OF REVIEW: To summarize the current knowledge on the origin and
      physiological function of T helper 17 (Th17) and discuss the contrasting results
      pertaining to the role of Th17 and interleukin-17 (IL-17) in atherosclerosis.
      RECENT FINDINGS: Atherosclerosis is a chronic inflammatory arterial disease
      driven by both innate and adaptive immune responses to modified lipoproteins.
      Although initial studies have focused on the role of Th1 and Th2 responses in
      atherosclerosis, more recent findings identified atheroprotective roles for
      several subsets of regulatory T cells. Th17 represents a new T-cell lineage with
      important roles in the clearance of pathogenic bacteria and fungi. The increase
      of Th17 and IL-17 has been recently linked to the pathogenesis of several
      autoimmune diseases. However, its role in chronic inflammatory diseases such as
      atherosclerosis remains poorly understood. The few studies available on this
      topic have generated contrasting results, which could be attributed to different
      approaches used on various mouse models. SUMMARY: IL-17 seems to have a
      modulatory role in atherosclerosis. Future studies are needed to better determine
      the molecular mechanisms involved in this regulation and examine whether
      targeting IL-17 pathway will be useful to treat cardiovascular diseases.

PMID- 20683329
TI  - More than just infections: an update on primary immune deficiencies.
AB  - PURPOSE OF REVIEW: The general pediatrician should be empowered to utilize
      continuity of care for the recognition of unusual or severe patterns of
      infection. With the burgeoning field of genetics, primary immune deficiencies
      (PIDs) can be diagnosed and treated earlier to provide better outcomes for
      patients and families. Improved treatment modalities have redefined expectations
      for many infants born with PIDs. RECENT FINDINGS: The prevalence of PIDs
      increases as researchers discover novel immunodeficiency syndromes and as
      clinicians increasingly recognize and diagnose nuanced presentations of
      immunodeficiency. Novel immunodeficiency syndromes associated with mutations in
      DOCK8, CARD9, and PRKDC recently have been described. For the first time in the
      United States, newborns from an entire state were screened for lymphopenia,
      allowing potentially life-saving early diagnosis of the most severe forms of PID
      before the onset of symptoms. Hematopoietic stem cell transplantation (HSCT) and
      gene therapy continue to be evaluated as curative treatments with increasing
      success rates for some of the most severe PIDs. SUMMARY: The field of PID
      continues to expand and advancements have been made in earlier diagnosis and
      screening. Comparative effectiveness research into treatment modalities offered
      to patients with PID is leading to a better understanding of optimal therapies
      for specific PIDs. In the meantime, the advocacy efforts of established and
      emerging PID networks promote excellence in clinical recognition and treatment of
      PIDs in children.

PMID- 20683330
TI  - Peanut allergy.
AB  - PURPOSE OF REVIEW: To highlight recent advances in management of peanut allergy.
      RECENT FINDINGS: Peanut allergy presents during early childhood. The prevalence
      of peanut allergy in children in developed countries appears to be increasing.
      Several factors, such as peanut-specific or environmental, are hypothesized as
      contributing to increased prevalence. However, there is no consensus on this
      matter. Component-related diagnostic tests are being explored to characterize
      clinical sensitivity. Currently, the primary treatment includes avoidance of
      peanut and immediate treatment of anaphylaxis. Recent peanut oral immunotherapy
      (OIT) trials achieved successful desensitization to peanuts in study
      participants, which may benefit many patients. Newer prospective studies are
      exploring effects of early high-dose peanut protein introduction versus avoidance
      in high-risk infants and development of peanut tolerance [Learning Early About
      Peanut Allergy (LEAP) study]. Several other immunotherapeutic approaches are
      being investigated in animal models. SUMMARY: There is no cure for peanut
      allergy. Peanut oral immunotherapy offers a potential treatment for
      desensitization.

PMID- 20683331
TI  - Recent developments in philosophy of mind and psychopathology.
AB  - PURPOSE OF REVIEW: This review covers recent books and articles on the perennial
      problem of how mind and brain work together to produce psychiatric symptoms.
      RECENT FINDINGS: Discussed in this article are research on predictors of anxiety
      disorders, evidence relating to agency and sense of self-ownership, the extended
      mind hypothesis, and brain differences in genders of moral sensitivity. SUMMARY:
      Advances in brain sciences continue, but psychiatry would do well to work with
      philosophers in the field of philosophy of mind.

PMID- 20683332
TI  - Detecting and defusing cognitive traps: metacognitive intervention in
      schizophrenia.
AB  - PURPOSE OF REVIEW: Until recently, psychological therapy for schizophrenia was
      considered harmful or inefficient by many clinicians. The reservation against
      psychotherapy is partly rooted in the assumption that delusions in particular and
      schizophrenia in general are not amenable to psychological understanding and
      represent 'utter madness'. However, meta-analyses suggest that cognitive
      intervention is effective in ameliorating schizophrenia symptoms. In addition,
      evidence has accumulated that cognitive biases, such as jumping to conclusions,
      are involved in the pathogenesis of schizophrenia positive symptoms, particularly
      delusions. A recently developed group program, called metacognitive training
      (MCT), is presented targeting these biases. MCT is a hybrid of psychoeducation,
      cognitive remediation and cognitive-behavioural therapy. RECENT FINDINGS: This
      review introduces new evidence on cognitive biases involved in the pathogenesis
      of schizophrenia and demonstrates how the MCT raises the patients'
      (metacognitive) awareness to detect and defuse such 'cognitive traps'. At the
      end, a new individualized variant entitled MCT+ is presented targeting individual
      delusional ideas. Finally, empirical results are summarized that speak in favour
      of the feasibility and efficacy of MCT. SUMMARY: Recent studies assert marked
      cognitive biases in schizophrenia. MCT has evolved as a feasible and effective
      complement of standard psychiatric treatment.

PMID- 20683333
TI  - Comparison of sevoflurane volatile induction/maintenance anaesthesia and propofol
      remifentanil total intravenous anaesthesia for rigid bronchoscopy under
      spontaneous breathing for tracheal/bronchial foreign body removal in children.
AB  - BACKGROUND AND OBJECTIVE: Foreign body aspiration is a life-threatening
      condition, with children under 3 years of age most at risk. This study was
      designed to compare the clinical characteristics of sevoflurane volatile
      induction/maintenance anaesthesia (VIMA) and propofol-remifentanil total
      intravenous anaesthesia (TIVA) for children undergoing rigid bronchoscopy under
      spontaneous breathing for tracheal/bronchial foreign body removal. METHODS: Sixty
      four children undergoing rigid bronchoscopy were allocated randomly to receive
      sevoflurane (Group VIMA; n = 32) or propofol-remifentanil (Group TIVA, n = 32)
      between 2007 and 2009. Respiratory rate, heart rate and mean blood pressure were
      compared at the time points including baseline level (T 0); laryngoscopy (T
      lary); insertion of rigid bronchoscope (T bron); 5, 10 and 20 min during
      procedure (T 5 min, T 10 min, T 20 min); the end of procedure (Tend) and
      discharge (T dis). Induction time, emergence time, intubating condition scores
      and the incidence of adverse events were compared. RESULTS: Time for loss of
      consciousness (Group VIMA 95.6 +/- 15.2 s vs. Group TIVA 146.2 +/- 26.9 s, P <
      0.05), time of Bispectral Index value decreased to 40 (Group VIMA 115.3 +/- 16.5
      s vs. Group TIVA 160.4 +/- 25.8 s, P < 0.05) and emergence time (Group VIMA 10.5
      +/- 2.6 min vs. Group TIVA 16.9 +/- 3.1 min, P < 0.05) in Group VIMA were
      significantly shorter than those in Group TIVA. Intubating condition scores
      between the two groups were comparable (8.1 +/- 0.9 in Group VIMA vs. 8.1 +/- 1.0
      in Group TIVA). The incidence rates of breath holding (Group VIMA 6.25% vs. Group
      TIVA 31.25%, P < 0.05) and desaturation (Group VIMA 15.63% vs. Group TIVA 37.50%,
      P < 0.05) in Group VIMA were significantly lower than those in Group TIVA. Heart
      rate, mean blood pressure and respiratory rate were significantly higher in Group
      VIMA than in Group TIVA. CONCLUSION: Compared with propofol-remifentanil TIVA,
      sevoflurane VIMA provides more stable haemodynamics and respiration, faster
      induction and recovery and higher incidence of excitement in paediatric patients
      undergoing tracheal/bronchial foreign body removal under spontaneous breathing.

PMID- 20683334
TI  - Reversal of rocuronium-induced neuromuscular blockade with sugammadex compared
      with neostigmine during sevoflurane anaesthesia: results of a randomised,
      controlled trial.
AB  - BACKGROUND AND OBJECTIVE: Sugammadex, a modified gamma-cyclodextrin, is a
      selective relaxant-binding agent designed to reverse the effects of the steroidal
      neuromuscular blocking agents rocuronium or vecuronium. This study compared the
      efficacy of sugammadex and neostigmine for reversal of neuromuscular blockade
      induced by rocuronium for facilitating elective surgery. METHODS: This
      randomised, multicentre, parallel-group trial included 98 adult patients.
      Patients received intravenous propofol for induction followed by sevoflurane
      maintenance anaesthesia. Neuromuscular blockade was monitored using
      acceleromyography and a train-of-four (TOF) mode of stimulation. Patients were
      randomly allocated to receive sugammadex 2.0 mg kg(-1) or neostigmine 50 microg
      kg (-1) (with glycopyrrolate 10 microg kg(-1)) at reappearance of the second
      response of the TOF (mean 16% twitch height of first response) after the last
      dose of rocuronium. Safety was evaluated by assessing adverse events, laboratory
      variables and vital signs. RESULTS: Time to recovery of the TOF ratio of 0.9
      after sugammadex compared with neostigmine was significantly shorter (P <
      0.0001), being 1.5 versus 18.6 min (geometric means). Predictability of response
      was greater with sugammadex than neostigmine: with 98% of sugammadex patients
      versus 11% of neostigmine patients recovering to a TOF ratio of 0.9 within 5 min.
      There were no clinical events related to residual neuromuscular blockade or
      reoccurrence of blockade. Serious adverse events were observed in two sugammadex
      treated patients and in three neostigmine-treated patients, respectively, but
      none were considered related to study drugs. CONCLUSION: Sugammadex achieved
      significantly faster recovery of neuromuscular function after rocuronium to a TOF
      ratio of 0.9 compared with neostigmine (Clinicaltrials.gov identifier:
      NCT00451217).

PMID- 20683335
TI  - High BMI in children as a risk factor for intraoperative hypotension.
AB  - INTRODUCTION: childhood obesity is a risk factor for many perioperative
      complications. Hypotension is a well described complication of general
      anaesthesia in both adults and children. This observational study compared the
      incidence of preincision hypotension (PIH) between children with high BMI and
      lean controls. METHODS: children aged 2-17 years undergoing noncardiac procedures
      were classified into high or normal BMI groups. The incidence of PIH was then
      compared between the two groups using SBP data abstracted from our electronic
      anaesthesia monitoring system. Binary logistic regression was used to examine
      factors associated with the likelihood of PIH. RESULTS: the study population was
      19 400 children (54% boys) with a mean (SD) age of 8.3 +/- 4.7 years and BMI of
      19.3 +/- 5.7 kg m(-2). Most (94.7%) of the patients were elective American
      Society of Anesthesiology I-II (79.7%) procedures. Single episode of PIH occurred
      in 36.8% of patients, whereas 8.3% had at least three episodes of PIH. PIH was
      more frequent in children with high BMI than their lean peers (40.9 vs. 31.4%, P
      < 0.001). Independent predictors of PIH were high BMI, high American Society of
      Anesthesiology status, propofol coinduction, baseline hypotension, age and
      preincision duration. CONCLUSION: these results imply that children with high BMI
      have a higher incidence of hypotension than their lean peers following induction
      of anaesthesia for noncardiac procedures.

PMID- 20683336
TI  - Task-shifting of antiretroviral delivery from health care workers to persons
      living with HIV/AIDS: clinical outcomes of a community-based program in Kenya.
AB  - OBJECTIVES: To assess whether community-based care delivered by people living
      with HIV/AIDS (PLWAs) could replace clinic-based HIV care. DESIGN: Prospective
      cluster randomized controlled clinical trial. SETTING: Villages surrounding 1
      rural clinic in western Kenya. SUBJECTS: HIV-infected adults clinically stable on
      antiretroviral therapy (ART). INTERVENTION: The intervention group received
      monthly Personal Digital Assistant supported home assessments by PLWAs with
      clinic appointments every 3 months. The control group received standard of care
      monthly clinic visits. MAIN OUTCOMES MEASURED: Viral load, CD4 count, Karnofsky
      score, stability of ART regimen, opportunistic infections, pregnancies, and
      number of clinic visits. RESULTS: After 1 year, there were no significant
      intervention-control differences with regard to detectable viral load, mean CD4
      count, decline in Karnofsky score, change in ART regimen, new opportunistic
      infection, or pregnancy rate. Intervention patients made half as many clinic
      visits as did controls (P < 0.001). CONCLUSIONS: Community-based care by PLWAs
      resulted in similar clinical outcomes as usual care but with half the number of
      clinic visits. This pilot study suggests that task-shifting and mobile
      technologies can deliver safe and effective community-based care to PLWAs,
      expediting ART rollout and increasing access to treatment while expanding the
      capacity of health care institutions in resource-constrained environments.

PMID- 20683337
TI  - Protective effect of the 1742(C/G) polymorphism of human cardiotrophin-1 against
      left ventricular hypertrophy in essential hypertension.
AB  - OBJECTIVE: Experimental and clinical evidence supports a role of cardiotrophin-1
      (CT-1) in the development of hypertensive left ventricular hypertrophy (LVH). The
      goal of this study was to investigate the relationship between human CT-1 genetic
      background and LVH in essential hypertension. METHODS: A total of 900 individuals
      were genotyped for the 1742(C/G) polymorphism of the human CT-1 gene. Serum CT-1
      levels were assessed by ELISA in 681 individuals. Left ventricular parameters
      were determined by two-dimensional echocardiography in 297 individuals. RESULTS:
      The prevalence of the GG genotype of the 1742(C/G) polymorphism was reduced in
      essential hypertension (8.4% in normotensive individuals, 4.9% in hypertensive
      patients, P = 0.046 versus CC/CG individuals) and in LVH (11.5% in
      nonhypertrophic normotensive individuals, 12.2% in nonhypertrophic hypertensive
      patients, 2.6% in hypertensive patients with LVH, P = 0.008 versus CC/CG
      individuals). Apart from this, GG individuals presented lower serum concentration
      of CT-1 (GG, 147.1 +/- 10.5 fmol/ml; CC/CG, 187.1 +/- 4.8 fmol/ml; P = 0.036) and
      left ventricular mass index (GG, 91 +/- 6 g/m; CC/CG, 119 +/- 3 g/m; P = 0.002).
      Multivariate analyses showed that the 1742(C/G) polymorphism was a significant
      determinant of both left ventricular mass index and serum CT-1, after adjusting
      for confounding factors. Finally, in-vitro studies supported the functionality of
      the 1742(C/G) polymorphism. CONCLUSION: Our results indicate that the 1742(C/G)
      polymorphism of the human CT-1 gene is associated with LVH in hypertension and
      that the GG genotype may have a protective role. It is suggested that CT-1 is one
      of the mediators of this association.

PMID- 20683338
TI  - Long-term reduction in aortic stiffness: a 5.3-year follow-up in routine clinical
      practice.
AB  - BACKGROUND: Whether a direct blood pressure-independent reduction in aortic
      stiffness can occur after several years of antihypertensive treatment has never
      been unequivocally demonstrated. METHOD: In this observational study, performed
      under conditions of routine clinical practice, we included 97 patients (age 63 +/
      11 years) with treated essential hypertension who attended the outpatient
      hypertension clinic of a university hospital, had a significant blood pressure
      (BP) lowering under treatment before the first measurement of aortic stiffness,
      and had at least one additional measurement of aortic stiffness during follow-up.
      Aortic stiffness and carotid pulse pressure (PP) were determined through carotid
      femoral pulse wave velocity (PWV) and applanation tonometry, respectively.
      RESULTS: A linear mixed model showed that the reduction in PWV (from 14.2 +/- 4.2
      to 11.0 +/- 2.4 m/s; P < 0.0001) over a long follow-up (mean delay 5.3 +/- 1.3
      years) was associated with a significant reduction in central SBP (from 132 +/-
      22 to 122 +/- 16 mmHg; P < 0.0001) and central PP (from 59 +/- 22 to 54 +/- 14; P
      < 0.001), contrasting with a smaller change in brachial SBP (from 132 +/- 17 to
      129 +/- 16 mmHg; P < 0.02) and no change in brachial PP. In multivariate
      analysis, the decrease in PWV (-0.70 +/- 0.07 m/s per year; P < 0.0001) was only
      slightly explained by the reduction in mean blood pressure. By contrast, the
      decrease in central PP (-0.83 +/- 0.41 mmHg per year; P = 0.043) was largely
      explained by the reduction in PWV. CONCLUSION: These results indicate that a
      large and sustained decrease in aortic stiffness can be obtained in treated
      hypertensive patients under conditions of routine clinical practice. These
      changes likely represent a delayed response to the long-term normalization of BP
      and cardiovascular risk factors, through arterial remodeling.

PMID- 20683339
TI  - Amiloride lowers arterial pressure in cyp1a1ren-2 transgenic rats without
      affecting renal vascular function.
AB  - OBJECTIVE: The epithelial sodium channel (ENaC) is expressed in the renal
      vasculature, where it may be involved in the control of vascular tone and
      arterial pressure. Using a rat model with an inducible mouse renin transgene
      (cyp1a1ren-2 transgenic rats), we tested the hypothesis that stimulation of the
      renin-angiotensin-aldosterone system (RAAS) for 3 weeks is associated with an
      impairment of renal vascular function that is sensitive to treatment with the
      ENaC blocker amiloride. METHODS: Rats were randomized to control, transgene
      induction, or transgene induction plus amiloride treatment (n = 7-10 per group).
      Additional control animals were treated with amiloride. Arterial pressure was
      measured telemetrically. Sodium balance was determined in metabolic cages. Renal
      vascular function was investigated in vitro (wire myography) and in vivo
      (ultrasound flow probe). ENaC mRNA expression was determined by real-time PCR.
      RESULTS: Transgene induction caused an increase in plasma aldosterone levels
      associated with a sustained elevation in arterial pressure. Amiloride elicited a
      transient decrease in renal sodium balance and effectively lowered arterial
      pressure. Neither transgene induction nor amiloride treatment significantly
      affected phenylephrine or acetylcholine-induced renal vascular responses.
      Similarly, small renal artery compliance and renal vascular resistance remained
      unaltered. Amiloride treatment caused an increase in alpha-ENaC mRNA abundance in
      renal cortical tissue but not in intrarenal arteries. CONCLUSION: Amiloride
      reduces arterial pressure in cyp1a1ren-2 transgenic rats in association with
      increased renal sodium excretion without affecting renal vascular function. In
      this model of hypertension sustained activation of the RAAS does not lead to
      increased ENaC expression in small intrarenal arteries.

PMID- 20683340
TI  - The aldosterone-renin ratio based on the plasma renin activity and the direct
      renin assay for diagnosing aldosterone-producing adenoma.
AB  - BACKGROUND: The screening for primary aldosteronism is based on the aldosterone
      renin ratio calculated with the plasma renin activity (PRA) value as denominator.
      A direct measurement of active renin (DRA) is being used as an alternative to
      PRA, but its diagnostic performance remains unclear. METHOD: We, therefore
      compared, head-to-head, the aldosterone-renin ratio based on PRA with that based
      on DRA, at baseline and after captopril administration, for identifying
      aldosterone-producing adenoma (APA) in 251 patients of the Primary Aldosteronism
      Prevalence in hYpertension Study (PAPY). The area under the receiver operator
      characteristics curves was used for estimating the accuracy of the aldosterone
      renin ratio based on either renin assay for identifying APA and for the
      comparison between tests. RESULTS: The rate of primary aldosteronism was 13.2%;
      6.4% of the patients had an APA and 6.8% idiopathic hyperaldosteronism; 218
      (86.8%) had primary hypertension. The area under the receiver operator
      characteristics curve for identifying APA was higher than 0.50 for the
      aldosterone-renin ratio based on both renin values (0.870 +/- 0.058 for DRA and
      0.973 +/- 0.028 for PRA) (P < 0.0001 for both) and did not differ significantly
      between the aldosterone-renin ratios calculated with either renin assay. For the
      aldosterone-renin ratio based on DRA, the optimal cutoff value for identifying
      APA was 27.3 ng/mIU, remarkably similar to that previously determined for the
      aldosterone-renin ratio based on PRA. CONCLUSION: Thus, the aldosterone-renin
      ratio based on DRA is a valuable alternative to that based on PRA for detecting
      APA.

PMID- 20683341
TI  - Increased levels of oxidative stress, subclinical inflammation, and myocardial
      fibrosis markers in primary aldosteronism patients.
AB  - BACKGROUND: Patients with primary aldosteronism experience greater left
      ventricular hypertrophy and a higher frequency of cardiovascular events than do
      essential hypertensive patients with comparable blood pressure levels.
      Aldosterone has been correlated with increased oxidative stress, endothelial
      inflammation, and fibrosis, particularly in patients with heart disease. AIM: To
      evaluate oxidative stress, subclinical endothelial inflammation, and myocardial
      fibrosis markers in patients with primary aldosteronism and essential
      hypertension. DESIGN AND INDIVIDUALS: We studied 30 primary aldosteronism
      patients and 70 control essential hypertensive patients, matched by age, sex and
      median blood pressure. For all patients, we measured the serum levels of
      aldosterone, plasma renin activity, malondialdehyde (MDA), xanthine oxidase,
      metalloproteinase-9, ultrasensitive C-reactive protein and amino terminal
      propeptides of type I (PINP), and type III procollagen. We also evaluated the
      effect of PA treatment in 19 PA individuals. RESULTS: PA patients showed elevated
      levels of MDA (1.70 +/- 0.53 versus 0.94 +/- 0.65 MUmol/l, P <0.001) and PINP
      (81.7 +/- 50.6 versus 49.7 +/- 27 mg/l, P = 0.002) compared with essential
      hypertensive controls. We found a positive correlation between MDA, PINP, and the
      serum aldosterone/plasma renin activity ratio in primary aldosteronism patients.
      Clinically, treating primary aldosteronism patients decreased MDA and PINP
      levels. CONCLUSION: We detected higher levels of MDA and PINP in primary
      aldosteronism patients, suggesting increased oxidative stress and myocardial
      fibrosis in these individuals. Treating primary aldosteronism patients reduced
      MDA and PINP levels, which may reflect the direct effect of aldosterone greater
      than endothelial oxidative stress and myocardial fibrosis, possibly mediated by a
      mineralocorticoid receptor.

PMID- 20683342
TI  - Early thoracic aorta enlargement in asymptomatic individuals at risk for
      cardiovascular disease: determinant factors and clinical implication.
AB  - OBJECTIVES: We analyzed, in above-average risk asymptomatic individuals, the
      factors determining early thoracic aorta enlargement. METHODS: Ascending aortic
      diameter (AAD) was measured with noncontrast multidetector computed tomography in
      345 participants (mean age 56 years; 78% men) without cardiovascular disease. We
      analyzed the associations of AAD with risk factors and Framingham risk score
      (FRS), multidetector computed tomography-assessed coronary artery calcium (CAC),
      and ultrasound interrogation of plaque presence at five sites (right and left
      carotid arteries, right and left femoral arteries, and abdominal aorta), the
      number of diseased sites with presence of plaque being counted from 0 to 5.
      RESULTS: AAD was positively associated with age (P < 0.001), male sex (P < 0.01),
      body surface area (BSA; P < 0.001), hypertension (P < 0.001), systolic and
      diastolic blood pressures in individuals without antihypertensive medication (P <
      0.05, P < 0.01), and FRS (P < 0.001). AAD was positively associated with CAC
      score after adjusting for age, sex, and BSA (P < 0001) or for FRS and BSA (P <
      0.001). AAD was higher in the presence of three, four, or five than in the
      presence of no, one, or two diseased sites with plaque, after adjusting for age,
      sex, and BSA (P < 0.05) or for FRS and BSA (P < 0.001). When participants were
      divided into subsets by AAD tertiles and by number of sites with plaque, FRS and
      CAC score were greatest in individuals with AAD top tertile and 3-5 sites with
      plaque and lowest in those with AAD bottom tertile and 0-2 sites with plaque (P <
      0.001). CONCLUSION: These findings suggest that thoracic ascending aorta
      dilatation is related to hypertension and represents a part of a generalized
      atherosclerotic process of the entire vasculature.

PMID- 20683344
TI  - Regenerative medicine: basic concepts, current status, and future applications.
AB  - A recent report demonstrated that a laboratory-grown neobladder tissue could be
      successfully used for cystoplasty in young patients with myelomeningocele who
      were otherwise healthy. This remarkable achievement portends well for the
      application of tissue engineering/regenerative medicine technologies to the
      treatment of end-organ failure due to a variety of causes (ie, congenital,
      acquired, age or disease related). Nonetheless, the broader clinical use of these
      groundbreaking technologies awaits improved understanding of endogenous
      regenerative mechanisms, more detailed knowledge of the boundary conditions that
      define the current limits for tissue repair and replacement in vivo, and the
      parallel development of critical enabling technologies (ie, improved cell source,
      biomaterials, bioreactors). This brief report will review a number of the most
      salient features and recent developments in this rapidly advancing area of
      medical research and detail some of our own experience with bladder and skeletal
      muscle regeneration and replacement as examples that highlight both the promise
      and challenges facing regenerative medicine/tissue engineering.

PMID- 20683343
TI  - Strategies for vascularization of polymer scaffolds.
AB  - Biocompatible, degradable polymer scaffolds combined with cells or biological
      signals are being investigated as alternatives to traditional options for tissue
      reconstruction and transplantation. These approaches are already in clinical use
      as engineered tissues that enhance wound healing and skin regeneration. The
      continued enhancement of these material strategies is highly dependent on the
      ability to promote rapid and stable neovascularization (new blood vessel
      formation) within the scaffold. Whereas neovascularization therapies have shown
      some promise for the treatment of ischemic tissues, vascularization of polymer
      scaffolds in tissue engineering strategies provides a unique challenge owing to
      the volume and the complexity of the tissues targeted. In this article, we
      examine recent advances in research focused on promoting neovascularization in
      polymer scaffolds for tissue engineering applications. These approaches include
      the use of growth factors, cells, and novel surgical approaches to both enhance
      and control the nature of the vascular networks formed. The continued development
      of these approaches may lead to new tissue engineering strategies for the
      generation of skin and other tissues or organs.

PMID- 20683345
TI  - Cardiac involvement in patients with hematologic malignancies.
AB  - Authors have reviewed literature about the management of patients with
      cardiologic disease occurring secondary to hematologic pathology itself or its
      therapy, with a focus on infiltration of myocardium in acute and chronic
      leukemia, lymphoma, multiple myeloma, and hypereosinophilic syndrome. Moreover,
      they evaluated chemotherapy-associated toxicity, particularly for new drugs such
      as monoclonal antibody therapy, tyrosine kinase inhibitors, arsenic trioxide,
      bortezomib, and epigenetic therapy. In fact, cardiac toxicity may range from
      asymptomatic subclinical abnormalities, such as electrocardiographic changes and
      left ventricular ejection decline, to life-threatening events and lead to
      chemotherapy dose reduction and delay and, in some cases, for patients with
      severe side effects, discontinuation of treatment. Finally, they discussed on the
      identification of early markers of cardiac injury and on cardiac stem cell
      therapy as a promising approach to facilitate myocardial regeneration.

PMID- 20683346
TI  - Using a type 1 collagen-based system to understand cell-scaffold interactions and
      to deliver chimeric collagen-binding growth factors for vascular tissue
      engineering.
AB  - Vascular tissue engineering should provide more biocompatible and functional
      conduits than synthetic vascular grafts. Understanding cell-scaffold interactions
      and developing an efficient delivery system for growth factors and other
      biomolecules to control the signaling between the cells and the scaffold are
      fundamental issues in a wide range of tissue engineering research fields. Type 1
      collagen is a natural scaffold extensively used in vascular tissue engineering
      and is a widely used vehicle in biomolecule delivery. In this article, we will
      discuss type 1 collagen as a vascular tissue engineering scaffold, describe
      strategies for elucidating the interaction between cells and type 1 collagen
      scaffolds using various imaging techniques, and summarize our work on the
      development of a chimeric collagen-binding growth factor-based local delivery
      system.

PMID- 20683347
TI  - Design of a bioartificial pancreas(+).
AB  - INTRODUCTION: In type 1 diabetes, the beta-cells that secrete insulin have been
      destroyed such that daily exogenous insulin administration is required for the
      control of blood glucose in individuals with the disease. After the development
      of reliable techniques for the isolation of islets from the human pancreas, islet
      transplantation has emerged as a therapeutic option, albeit for only a few
      selected patients largely because there are not enough islets for the millions of
      patients requiring the treatment, and there is also the need to use
      immunosuppressive drugs to prevent transplant rejection. In 1980, the concept of
      islet immunoisolation by microencapsulation was introduced as a technique to
      overcome these 2 major barriers to islet transplantation. Microencapsulation of
      islets and transplantation in the peritoneal cavity was then described as a
      bioartificial pancreas. However, it is difficult to retrieve encapsulated islets
      transplanted in the peritoneal cavity, thus making it difficult to meet all the
      criteria for a bioartificial pancreas. A new design of a bioartificial pancreas
      comprising islets co-encapsulated with angiogenic protein in permselective
      multilayer alginate-poly-L-ornithine-alginate microcapsules and transplanted in
      an omentum pouch is described in this paper. MATERIALS AND METHODS: The
      multilayer alginate-poly-L-ornithine-alginate microcapsules are made with
      ultrapure alginate using poly-L-ornithine as a semipermeable membrane separating
      the 2 alginate layers. The inner alginate layer is used to encapsulate the
      islets, and the outer layer is used to encapsulate angiogenic protein, which
      would induce neovascularization around the graft within the omentum pouch.
      RESULTS: In in vitro studies, we found that both the wild-type and the heparin
      binding growth-associated molecule (HBGAM)-fibroblast growth factor-1 chimera can
      be encapsulated and released in a controlled and sustained manner from the outer
      alginate layer with a mean diameter in the range of 113 to 164 um when 1.25% high
      guluronic acid alginate is used to formulate this outer layer. DISCUSSION: We are
      currently performing in vivo experiments to determine the ability of angiogenic
      proteins released from this outer layer to induce neovascularization around the
      grafts in the omentum pouch. We will subsequently examine the effect of co
      encapsulation of islets with angiogenic protein on blood glucose control in
      diabetic animals. It is hoped that addition of tissue engineering to encapsulated
      islet transplantation will result in long-term survival of the islets and their
      ability to control blood glucose in type 1 diabetes without the necessity to use
      risky immunosuppressive drugs to prevent transplant rejection.

PMID- 20683349
TI  - Relationship between isometric and dynamic strength in recreationally trained
      men.
AB  - The purpose of this investigation was to examine the relationships between
      measures of maximal isometric force (peak force [PF]), rate of force development
      (RFD), vertical jump performance (VJ) and 1-repetition maximum (1RM) strength in
      recreationally trained men. The subjects in this study were 26 men ([mean +/-
      SD]: age 22 +/- 1 years; height 175 +/- 7 cm; mass 90 +/- 10 kg). They were
      tested for PF using the isometric midthigh pull exercise. The 1RM for the squat
      and bench press exercise were determined as a measure of dynamic strength.
      Explosive strength was measured as RFD from the isometric force-time curve.
      Correlations between the variables were calculated using Pearson product moment
      correlation coefficient. There was a nearly perfect correlation between measures
      of PF and 1RM squat (r = 0.97, p < 0.05) and 1RM bench press (r = 0.99, p <
      0.05). The correlations were very strong between VJ and PF (r = 0.72, p < 0.05)
      and 1RM bench press (r = 0.70, p < 0.05). There were also strong correlations
      between VJ and 1RM squat (r = 0.69, p < 0.05). There were no significant
      correlations with RFD. The results showed that isometric maximum strength
      determined during the isometric midthigh pull test correlated well with 1RM and
      VJ testing. However, RFD measured during the same test did not appear to
      correlate as well with other measures. The isometric midthigh pull provides an
      efficient method for assessing strength in recreationally trained individuals.
      Practitioners wishing to obtain performance data related to maximum strength may
      wish to consider isometric testing as a less time intensive method of testing.

PMID- 20683348
TI  - Promises and pitfalls in erythopoietin-mediated tissue protection: are
      nonerythropoietic derivatives a way forward?
AB  - The essential biological role of erythropoietin (EPO) in maintaining erythrocyte
      mass has been well understood for many years. Although EPO is required for the
      maturation of red cells, it also has strong procoagulant effects on the vascular
      endothelium and platelets, which limit erythrocyte losses after hemorrhage. Like
      other members of the type 1 cytokine superfamily, EPO has multiple biological
      activities. For the past 10 years, multiple investigators have shown that EPO
      acts as a locally produced antagonist of proinflammatory cytokines that are
      generated by the innate immune response in response to infection, trauma, or
      metabolic stress. Specifically, EPO inhibits apoptosis of cells surrounding a
      locus of injury, reduces the influx of inflammatory cells, and recruits tissue
      specific stem cells and endothelial progenitor cells. Available evidence suggests
      that these multiple, nonerythropoietic effects of EPO are mediated by a tissue
      protective receptor (TPR) that is distinct from the homodimeric receptor
      responsible for erythropoiesis. Notably, activation of the TPR requires a higher
      concentration of EPO than is needed for maximal erythropoiesis. Unfortunately,
      these higher concentrations of EPO also stimulate hematopoietic and procoagulant
      pathways, which can cause adverse effects and, therefore, potentially limit the
      clinical use of EPO for tissue protection. To circumvent these problems, the EPO
      molecule has been successfully modified in a variety of ways to interact only
      with the TPR. Early clinical experience has shown that these compounds appear to
      be safe, and proof of concept trials are ready to begin.

PMID- 20683350
TI  - Mechanical properties of weightlifting bars.
AB  - Weightlifting training and competition involves lifting a revolving shaft bar
      loaded with weights. The design of a bar and the location of the weights result
      in bar deformation during lifting tasks. Because there are many manufacturers of
      weightlifting bars, the actual deformation of a bar may vary, depending on the
      steel alloys used. A modified 4-point static bending test was used to assess
      deformation of 8 weightlifting bars and 1 general purpose weight training bar.
      The apparent stiffness of the bars was determined by plotting bending moment vs.
      bar deformation (the vertical height difference between the center vs. ends of
      the bar). All bars tested had an absence of hysteresis during cyclic loading and
      unloading in 50-kg increments (up to 220-kg total barbell weight), demonstrating
      pure elastic properties. At maximum loading, bar deformation was 4-5 cm. A large
      range existed for apparent stiffness. Based on apparent stiffness calculations,
      recommendations are made for which bars are suitable for weightlifting training
      and competition. The deformable nature of weightlifting and weight training bars
      should be considered before their use in exercise, sport, or research.

PMID- 20683351
TI  - Effect of whole-body vibration warm-up on bat speed in women softball players.
AB  - Whole-body vibration (WBV) may enhance human performance via augmented muscular
      strength and motor function if used before performance. Because warm-up is a
      crucial aspect of preparation for performance, it remains unknown if WBV may
      enhance bat speed. The purpose of this study was to investigate the effect of WBV
      warm-up on bat speed. Eleven National Collegiate Athletic Association division I
      and 11 recreationally trained female softball players volunteered to participate.
      Subjects randomly performed 3 different warm-up conditions consisting of WBV
      alone, dry swings alone (DS), and WBV with dry swings (WBVDS). Whole-body
      vibration was performed on a pivotal vibration platform at a frequency of 25 Hz
      and an amplitude of 13 mm for one 30-second bout. Thirty seconds after each warm
      up condition, 5 maximal bat swings were recorded. There was no significant (p >
      0.05) difference between groups by training status, and there was no significant
      (p > 0.05) difference between WBV (42.39 +/- 9.83 mph), DS (40.45 +/- 11.00 mph),
      or WBVDS (37.98 +/- 12.40 mph) conditions. These results indicate that WBV warm
      up may be used in place of DS to achieve similar bat speeds. Future research
      should investigate different combinations of WBV warm-up using various
      frequencies, durations, amplitudes, and rest times.

PMID- 20683352
TI  - Intragame blood-lactate values during ice hockey and their relationships to
      commonly used hockey testing protocols.
AB  - This study evaluated the on ice blood-lactate values during a division 1 ice
      hockey game in an attempt to demonstrate the highly variable nature of the game.
      Our hypothesis was that intragame blood-lactate (BLa) values would be highly
      variable and related to shift length. Six men (age = 20.4 + 1.8 years, body mass
      81.3 +8.7 kg) agreed to have fingerstick BLa samples taken at the completion of
      selected shifts (n = 35 samples) during the first and third periods of a division
      1 ice hockey game. Shift length including work and rest intervals were also
      recorded for each of these shifts. Blood-lactate values ranged from 4.4 to 13.7
      mmol.L with a mean value of 8.15 (+2.72) mmol.L. Shift length ranged from 55 to
      145 seconds with individual work intervals within the shifts ranging from 29 to
      102 seconds in length. Most shifts had either 1 or no play stoppages and rest to
      work intervals ranged from 0-1.66 (+0.53). These results further support the
      intense and variable nature of ice hockey and should help coaches develop more
      specific training and testing regimens to prepare for these demands. They also
      highlight the need for a validated and reliable test of repeated sprint ability
      for ice hockey players.

PMID- 20683353
TI  - Effect of functional isometric squats on vertical jump in trained and untrained
      men.
AB  - Functional isometrics (FIs) combine dynamic and isometric muscle actions and may
      hyperstimulate the nervous system leading to an enhanced postactivation
      potentiation (PAP) and improved subsequent performance. The purpose of this study
      was to investigate the impact of an FI squat on the countermovement vertical jump
      (CMVJ) in resistance trained and untrained men. Thirteen trained men (age: 22.8
      +/- 3.2 years, mass: 90.0 +/- 16.3 kg, and height: 178.9 +/- 7.1 cm) and 8
      untrained men (age: 28.5 +/- 5.9 years, mass: 101.5 +/- 23.0 kg, and height:
      177.0 +/- 4.8 cm) participated. On separate days, subjects performed CMVJs after
      2 different warm-up conditions. The warm-up conditions consisted of either 5
      minutes of low-intensity cycling or 5 minutes of low-intensity cycling plus a 3
      second FI squat with 150% of their 1 repetition maximum (1RM). A 2 x 3 repeated
      measures analysis of variance with Bonferroni post hoc revealed that when
      comparing the 2 warm-up conditions in the trained subjects, a significant
      increase (p < 0.05) in CMVJ occurred at 4 minutes (2.4 cm, +5.1%) post-FI squat.
      This increase was maintained when subjects were retested at 5 minutes post (2.6
      cm, + 5.5%). No significant difference in CMVJ was detected in the untrained
      group (p = 0.49). Results support the addition of an FI squat performed at 150%
      of 1RM to a low-intensity cycling warm-up to enhance PAP in resistance trained
      but not in untrained men as measured by CMVJ. Practically, adding functional
      isometrics to a warm-up scheme may significantly enhance acute, short-term power
      output in resistance trained men.

PMID- 20683354
TI  - Effect of remote voluntary contractions on knee extensor torque and rate of
      velocity development.
AB  - Remote voluntary contractions (RVCs) are described as a muscle action of the
      prime mover while performing a simultaneous muscle action with another part of
      the body. Previous studies have shown that RVCs may elicit augmented performance
      of the prime mover. The purpose of this study was to evaluate the effect of RVCs
      on knee extensor rate of velocity development (RVD) and peak torque. Fourteen men
      and 16 women who were regularly active and free of any knee pathology for the
      past year took part in this study. Subjects performed 3 maximal dynamic knee
      extensions at 3 velocities with and without an RVC condition. The RVC condition
      consisted of holding hand dynamometers in each hand and maximally gripping while
      performing a maximal knee extension movement. The NO-RVC condition was the same
      only without gripping. Men produced greater peak torque and RVD than did women
      across speeds and conditions. Analysis demonstrated that RVC had no effect on
      knee extension peak torque, but RVD decreased in the RVC condition (NO-RVC
      2,012.07 [46.52] degrees xs-1xs-1; RVC 1,882.61 [51.84] degrees xs-1xs-1). Grip
      strength of the left hand at 180 degrees xs-1decreased from 42.03 (14.40) to
      38.83 (14.65) kg in the RVC condition. In conclusion, RVC should not be used when
      attempting to maximize RVD, because it may hinder results when performing a
      single joint movement.

PMID- 20683355
TI  - The acute effects of static stretching on the sprint performance of collegiate
      men in the 60- and 100-m dash after a dynamic warm-up.
AB  - Previous research has shown that static stretching has an inhibitory effect on
      sprinting performances up to 50 m. The purpose of this study was to see what
      would happen to these effects at longer distances such as those seen in
      competition. This study used a within-subjects design to investigate the effects
      of passive static stretching vs. no stretching on the 60- and 100-m sprint
      performance of college track athletes after a dynamic warm-up. Eighteen male
      subjects completed both the static stretching and the no stretching conditions in
      counterbalanced order across 2 days of testing. On each day, all subjects first
      completed a generalized dynamic warm-up routine that included a self-paced 800-m
      run, followed by a series of dynamic movements, sprint, and hurdle drills. At the
      end of this generalized warm-up, athletes were assigned to either a static
      stretching or a no-stretching condition. They then immediately performed 2 100-m
      trials with timing gates set up at 20, 40, 60, and 100 m. Results revealed a
      significant slowing in performance with static stretching (p < 0.039) in the
      second 20 (20-40) m of the sprint trials. After the first 40 m, static stretching
      exhibited no additional inhibition of performance in a 100-m sprint. However,
      although there was no additional time loss, athletes never gained back the time
      that was originally lost in the first portion of the trials. Therefore, in strict
      terms of performance, it seems harmful to include static stretching in the warm
      up protocol of collegiate male sprinters in distances up to 100 m.

PMID- 20683356
TI  - The influence of ratio and allometric scaling procedures for normalizing upper
      body power output in division I collegiate football players.
AB  - The purpose of the present study was to examine the differences in upper body
      power output among lineman and nonlineman division I collegiate football players
      and to examine the influence of 2 normalization procedures: (a) simple ratio
      scaling and (b) standardized allometric scaling. Ten lineman (mean +/- SD: age =
      19.3 +/- 1.6 years; height = 187.7 +/- 4.7 cm; mass = 127.7 +/- 13.3 kg) and 14
      nonlineman (19.6 +/- 1.4 years; 181.8 +/- 5.2 cm; 92.3 +/- 10.6 kg) performed a
      multiple repetition bench press power test at 50% of their 1 repetition maximum.
      Peak power (PP) was determined from a Tendo weightlifting analyzer that was
      attached to the barbell. The PP values were then analyzed under 3 conditions that
      included: (a) no scaling (absolute values), (b) ratio scaling (PP body mass), and
      (c) allometric scaling (PP body mass). The results indicated that the larger
      lineman demonstrated greater absolute PP values (p = 0.02); however, ratio
      scaling favored the smaller nonlineman group (p = 0.04). There were no
      differences in PP values between positions after the standardized allometric
      scaling procedure (p = 0.60). These findings indicated that the standardized
      allometric scaling procedure may be a more effective method for normalizing PP
      values among elite division I collegiate football players.

PMID- 20683357
TI  - Muller glia induce retinal progenitor cells to differentiate into retinal
      ganglion cells: Retraction.

PMID- 20683358
TI  - Thyroxine treatments do not correct inner ear defects in tmprss1 mutant mice.
AB  - Complete deficiency of a member of the type II transmembrane serine protease
      family, tmprss1 (also known as hepsin), is associated with severe to profound
      hearing loss in mice and a gross enlargement of the tectorial membrane in the
      cochlea. Levels of thyroxine in these mice have been shown to be significantly
      lower when compared with wild-type controls. As thyroxine is critical for inner
      ear development, we delivered thyroxine to these mice during the prenatal or
      postnatal stage of development. Both the treatments could not ameliorate hearing
      loss or correct deformities in the tectorial membrane of these mutant mice,
      suggesting that a deficiency in tmprss1 affects thyroxine responsiveness in the
      inner ear in vivo.

PMID- 20683359
TI  - Effect of primate bone marrow stromal cells on survival and neurite outgrowth.
AB  - We tested whether bone marrow stromal cells (BMSCs) could enhance the survival
      and neurite growth of dorsal root ganglia (DRG) through substrate effects or
      secreted factors. Our results showed that in DRG with BMSCs and BMSC-conditioned
      media cultures compared with DRG-fibroblast cultures, there was a significant
      increase in the number and length of, area covered by, and number of cells with
      definite neurites. In cytokine assays with conditioned media, vascular
      endothelial growth factor, granulocyte macrophage colony-stimulating factor, and
      IL-6 secreted by BMSCs may contribute to observed neurotrophic effects. These
      findings indicate that BMSCs of adult Macaca fascicularis increased neuronal
      survival and promoted neurite outgrowth of DRG by means of secretory factors.

PMID- 20683360
TI  - Moyamoya patients exhibit higher brain temperatures than normal controls.
AB  - The balance between heat production (metabolism) and heat removal (blood flow)
      helps in keeping the temperature of the brain constant. In patients with moyamoya
      disease, this balance may be disturbed. The purpose of this study was to assess
      the thermal pathophysiology of the brain in patients with moyamoya disease. The
      study included 12 consecutive patients with moyamoya disease and 10 controls.
      Temperature was measured by image postprocessing of diffusion-weighted images.
      Our noninvasive thermometry showed that the ventricular temperature of moyamoya
      disease patients was higher than that of normal controls. The mean temperature
      difference of 1.1 degrees C between the two groups was significant. Patients with
      moyamoya disease tend to have elevated ventricular temperatures, which may
      represent a mismatch between cerebral metabolism and perfusion.

PMID- 20683361
TI  - Sodium butyrate enhances the expression of baculovirus-mediated sodium/iodide
      symporter gene in A549 lung adenocarcinoma cells.
AB  - OBJECTIVE: Increased expression of sodium/iodide symporter (NIS) is required for
      reporter gene imaging and effective radioiodine treatment of tumor. We
      investigated whether increased accumulation of iodine can be induced by sodium
      butyrate through a newly developed baculoviral transfer of the human NIS (hNIS)
      gene in A549 human lung adenocarcinoma. METHODS: A recombinant baculovirus [Bac
      cytomegalovirus (CMV)-hNIS] encoding hNIS gene under the control of the CMV
      promoter was constructed. After A549 cells were transfected with Bac-CMV-hNIS in
      the presence of sodium butyrate, the expression of hNIS protein was detected by
      immunofluorescence and western blot analysis. The uptake and efflux of iodine
      were determined after the incubation of the transfected cells with I-iodide in
      the presence or absence of sodium butyrate. RESULTS: Immunocytochemical staining
      and western blot analysis showed increased hNIS protein expression in A549 cells
      transfected with Bac-CMV-hNIS after sodium butyrate treatment. Bac-CMV-hNIS
      transfected A549 cells accumulated up to about nine times more I than
      nontransfected cells; the amount of I uptake increased in a sodium butyrate in
      dose-dependent manner (P<0.001). However, rapid efflux of radioactivity was
      observed, with 50% lost during the first 2 min after I-containing medium had been
      replaced by a nonradioactive medium. CONCLUSION: Our results indicated that an
      improved efficiency of baculovirus-mediated hNIS reporter gene imaging in lung
      adenocarcinoma is possible with treatment with sodium butyrate. However,
      additional conditions need to be defined to reduce the rapid efflux of
      radioiodine for the purpose of radionuclide therapy.

PMID- 20683362
TI  - Comparison of efficacy of Tc-99m HIG and Tc-99m nanocolloid on sentinel lymph
      node mapping in patients with breast cancer.
AB  - BACKGROUND AND AIM: This study compared the effectiveness of Tc-99m human
      polyclonal immunoglobulin (HIG) and Tc-99m nanocolloid at detecting sentinel
      lymph nodes (SLNs) with lymphoscintigraphy and an intraoperative gamma-probe
      (IGP) in patients with early breast cancer. METHODS: The study group consisted of
      50 women; 25 patients each were given Tc-99m HIG or Tc-99m nanocolloid for
      lymphoscintigraphy. Then, intraoperative SLN localization with IGP was performed.
      The results of IGP, lymphoscintigraphy, blue dye injected just before surgery,
      and pathology were compared. RESULTS: In the Tc-99m HIG group, one patient had
      tumours in both breasts. In two patients, we could not detect SLNs with
      lymphoscintigraphy, although they were detected with IGP and blue dye. We found
      SLNs for all tumours with IGP. With the intraoperative blue dye, SLNs were
      identified for 25 tumours; for one tumour, no SLN was detected with blue dye. In
      the histopathological examination, 13 tumours showed metastasis in the SLN and in
      11 of these 13, there were also metastases in the axilla. One patient had a skip
      metastasis. In the Tc-99m nanocolloid group, SLNs were identified in 24 patients
      with lymphoscintigraphy. IGP found SLNs in 24 patients. The blue dye detected
      SLNs in all patients. On histopathological examination, 10 patients had
      metastasis in the SLN and there were also metastases in the axilla in all of
      these patients. CONCLUSION: Tc-99m HIG can be used in SLN detection with
      preoperative lymphoscintigraphy and IGP in early-stage breast cancer patients.

PMID- 20683363
TI  - High-throughput small animal PET imaging in cancer research: evaluation of the
      capability of the Inveon scanner to image four mice simultaneously.
AB  - The aim of this study was to assess the capability of small animal PET (SA-PET)
      devices to image four mice simultaneously to improve the throughput of SA-PET
      experiments in cancer research. A customized bed was designed to image up to four
      mice simultaneously. This bed can easily replace the bed provided by the
      manufacturer and is connected to an anaesthesia device. A mouse-sized phantom was
      imaged, mimicking simultaneous imaging of four mice with computation of recovery
      coefficients and spillover ratios (SORs). In addition, eight mice bearing
      subcutaneous tumours (human embryonal carcinoma, n=22 tumours) were
      simultaneously imaged in groups of four on an Inveon SA-PET scanner after
      injection of F-fluoro-D-glucose. Tumour activity (Bq/ml), as determined by the SA
      PET, was compared with ex-vivo counting. For a 5-mm rod, recovery coefficients
      were 1.15 and 1.05 for a phantom imaged at the central field of view or off
      centred on the customized bed, respectively. SORair and SORwater were 0.05 and
      0.04 for a phantom imaged alone and 0.15 and 0.06 for a phantom imaged with three
      additional scatter sources, respectively. Correlation between SA-PET and ex-vivo
      quantification was good (r=0.91, P<0.0001). The mean ratio of PET quantitative
      data and ex-vivo counting was equal to 0.9 (95% confidence interval: 0.70-1.09).
      New generation SA-PET may be suitable for simultaneously imaging four tumour
      bearing mice, although improvement in scatter correction efficiency appears
      necessary. The type of customized bed developed in this study could be easily
      adapted to other large-bore SA-PET scanners.

PMID- 20683364
TI  - Specificity of 99mTc-UBI for detecting infection foci in patients with fever in
      study.
AB  - Fever of unknown origin (FUO) represents a challenge to clinical medicine, and
      bacterial cultures have been considered the 'gold standard' in discriminating
      between fevers resulting from bacterial infection and sterile inflammations. In
      nuclear medicine, a synthetic radiolabeled antimicrobial peptide (Tc-UBI) is used
      to image the molecular localization of infectious microorganisms. OBJECTIVE: The
      aim of this research was to determine the absolute and relative frequencies of Tc
      UBI, by molecular imaging, to detect infection foci in patients with fever in
      study or FUO. METHODS: Images (207) from 196 patients with FUO acquired with Tc
      UBI and a Siemens gammacamera were read by two nuclear medicine physicians and
      classified as positive or negative for infection foci. The diagnostic value was
      corroborated with our gold standard, which comprises bacterial cultures of
      biopsies, blood and urine, plus laboratory studies, morphological images
      (radiographs, nuclear magnetic resonance, computed tomography) and the clinical
      history of each patient. The absolute and relative frequencies of Tc-UBI were
      calculated from the molecular images versus the gold standard. RESULTS: The
      specificity of Tc-UBI for localizing infection foci and for discarding sterile
      inflammation was 95.35%, the sensitivity was 97.52%, the positive predictive
      value was 96.72%, the negative predictive value was 96.47%, the accuracy was
      96.62%, and the observed agreement between the bacterial culture and the
      molecular image was 96.62% (P=0.0001). CONCLUSION: Considering that the absolute
      and relative frequencies are very high, we propose that, in the future, Tc-UBI
      molecular imaging could be the gold standard to detect infection sites and to
      discard sterile inflammation.

PMID- 20683365
TI  - Automated detection of left ventricular dyskinesis by gated blood pool SPECT.
AB  - OBJECTIVE: The ability to detect left ventricular (LV) apical dyskinesis, the
      hallmark of an aneurysm, is an important requirement of diagnostic cardiac
      imaging modalities that perform wall motion analysis. Our investigation assessed
      the ability of gated blood pool single-photon emission-computed tomography (GBPS)
      to automatically detect LV dyskinesis, using cardiac magnetic resonance (CMR) as
      the reference standard. MATERIALS AND METHODS: GBPS data were analyzed for 41
      patients with congestive heart failure or cardiomyopathy and compared with ECG
      gated TrueFISP CMR evaluations. An experienced nuclear cardiologist without the
      knowledge of quantitative GBPS or CMR results graded visual impressions of
      regional wall motion while examining cinematic playbacks of GBPS images. GBPS
      algorithms automatically isolated LV counts and computed regional phase (phi)
      values in each of 17 conventional American Heart Association LV segments. LV
      asynchrony was quantified by the two local measures: maximum apical phi
      difference (Deltaalpha), and standard deviation among apical phases (sigmaalpha),
      and by the five global measures: varphi histogram bandwidth (BWHistogram), phi
      histogram standard deviation (sigmaHistogram), Z-scores, Entropy, and Synchrony.
      For CMR data, an expert manually drew endocardial LV outlines to measure regional
      wall motion in 17 LV segments. RESULTS: Apical dyskinesis was present in nine
      patients. Among GBPS measurements, the method with the greatest accuracy for
      detecting dyskinesis was Deltaalpha (receiver operating characteristic area=95%).
      The only method with a sufficiently high kappa statistic to represent 'very good
      agreement' with CMR was Deltaalpha, with kappa=0.81. Deltaalpha was more
      sensitive in detecting dyskinesis than visual analysis (100 vs. 33%, P=0.01).
      CONCLUSION: Automatic GBPS computations accurately identified patients with LV
      dyskinesis, and detected dyskinesis more successfully than did visual analysis.

PMID- 20683366
TI  - Assessment of left ventricular dyssynchrony in patients with coronary artery
      disease during adenosine stress using ECG-gated myocardial perfusion single
      photon emission computed tomography.
AB  - OBJECTIVES: Some investigators have reported that left ventricular (LV)
      mechanical systolic and diastolic dyssynchrony occurs in coronary artery disease
      (CAD) patients without earlier myocardial infarction and narrow QRS complex
      duration. However, earlier studies evaluated LV dyssynchrony only at rest. The
      purpose of this study was to investigate LV dyssynchrony in CAD patients with
      preserved ejection fraction during adenosine stress using electrocardiogram-gated
      myocardial perfusion single-photon emission computed tomography (SPECT). METHODS:
      The study population included 18 CAD patients and 18 control subjects. CAD
      patients had significant stenosis in their coronary arteries by coronary
      angiogram without earlier myocardial infarction. SPECT images were acquired at
      rest and during stress with adenosine. The regional time to end systole (TES),
      time to peak ejection, the time from 0 to peak filling during the whole diastolic
      period (TPF1), and the time from end systole to peak filling during the whole
      diastolic period (TPF2) were obtained by using the Quantitative Gated SPECT
      software. The maximal difference (MD), which is the difference between the
      earliest and latest temporal parameter among 17 segments, was considered to
      represent LV dyssynchrony. RESULTS: MD-TES and MD-TPF1 during stress were
      significantly greater than those of rest in CAD patients (MD-TES: stress=242+/
      107 ms, rest=164+/-79 ms; P=0.005, MD-TPF1: stress=249+/-121 ms, rest=164+/-88
      ms; P=0.015) but there were no significant differences in control patients.
      CONCLUSION: LV dyssynchrony was shown in CAD with preserved ejection fraction
      during adenosine stress.

PMID- 20683367
TI  - Ophthalmic plastic and reconstructive surgery: 25th anniversary year.

PMID- 20683368
TI  - Palisaded encapsulated neuroma: an entity to consider in the differential
      diagnosis of the eyelid nodule. A case report.
AB  - A 58-year-old female presented to her ophthalmologist with a firm 5 mm * 5 mm
      painless nodule on her right eyelid that had been present for 4 years. The nodule
      was well encapsulated and was composed of spindled cells. The central portion of
      the tumor contained a neuroid cell population with tapered ends. The periphery of
      the neuroid cell population exhibited a palisading pattern. Myxoid stromal
      changes could be appreciated between the neuroid cell population and the capsule.
      Routine hematoxylin-eosin staining and S100, epithelial membrane antigen, and
      neurofilament were used to diagnose the nodule as palisaded and encapsulated
      neuroma, a benign peripheral nerve sheath tumor derived from Schwann cells.

PMID- 20683369
TI  - Melanocytic nevi of the tarsal conjunctiva: clinicopathologic case series with
      review of literature.
AB  - PURPOSE: To describe 4 patients with histopathologically confirmed tarsal
      conjunctival nevi and to review the literature regarding nevi in this location.
      METHODS: Clinicopathologic series of 4 cases diagnosed at the New York Eye and
      Ear Infirmary between January 1990 and April 2009. PubMed was searched for
      reported cases of tarsal conjunctival nevi. RESULTS: Four patients (mean age 44
      years, median 50 years, range 5-70 years) with tarsal conjunctival nevi were
      identified (3.4% of all histopathologically diagnosed conjunctival nevi). These
      lesions presented in adulthood (3 cases) and were associated with
      elevation/nodularity (3 cases), gray-brown coloration (3 cases), physician
      documented growth (1 case), madarosis (1 case), and intrinsic vessels (1 case).
      Histopathology revealed combined nevi centered in the posterior lamella of the
      eyelid, predominantly in peri-Meibomian gland distribution. Review of the
      literature identified 10 previously reported cases of tarsal nevi with detailed
      clinicopathologic correlation in 3 of these patients. CONCLUSIONS: Tarsal
      conjunctival nevi are rare. Adult presentation; subjective and objective evidence
      of growth; and associated inflammation, vascularity, and eyelid margin changes
      may make clinical distinction of tarsal nevi from melanoma challenging. Biopsy,
      therefore, is prudent as histopathology alone allows documentation of the benign
      nature of these lesions.

PMID- 20683370
TI  - Delayed orbital hematoma after lateral canthoplasty.
AB  - A 76-year-old man was referred to the oculoplastic surgery service with a
      retrobulbar hemorrhage 1 day after intraocular surgery. A canthotomy and inferior
      cantholysis was performed. The patient then developed a new orbital hematoma in
      the region of the canthotomy 14 days later. The patient was treated
      conservatively with warm compresses and close observation with continued
      resolution of the secondary hematoma. Visual complications from the secondary
      hematoma may have been avoided by delaying closure of the initial canthotomy
      wound. Ophthalmologists should be aware of the risk of bleeding after lateral
      canthal procedures, particularly in patients who have already presented with
      ocular or periocular hemorrhagic complications. A brief review of orbital
      hemorrhage following eyelid surgery is provided.

PMID- 20683371
TI  - Intubation of the ostium and nasolacrimal duct with a single self-linking
      silicone stent in external dacryocystorhinostomy.
AB  - PURPOSE: To describe a stent placement method that eliminates stent prolapse in
      external dacryocystorhinostomy. METHODS: A retrospective, institutional review
      board- approved case series of patients undergoing external dacryocystorhinostomy
      with an alternative stenting method. Following anastomosis of the posterior
      flaps, one arm of a Crawford silicone stent is passed through each canaliculus.
      Both arms are then passed through the nasolacrimal duct and retrieved in the
      inferior meatus. The 2 distal arms are redirected in the nose; one arm is looped
      around the proximal portions within the lacrimal sac and tied to the second arm.
      The stent is self-linked around the inferior turbinate. RESULTS: Nine patients
      underwent external dacryocystorhinostomy with alternative stenting. None
      experienced postoperative stent prolapse. At last follow-up (average, 38 months;
      range, 5-102 months), 8 patients reported resolution of tearing and exhibited
      normal dye clearance. On compression of the lacrimal sac, none of these 8
      patients exhibited reflux of stagnant tears or dye through the canaliculi.
      CONCLUSIONS: This alternative method improves stent retention by using the
      inferior turbinate as a stopper to eliminate stent prolapse. The self-linking
      nature obviates the need and expense of additional biomedical devices.

PMID- 20683372
TI  - Lateral tarsal fixation in Caucasians.
AB  - PURPOSE: To present the microscopic lateral tarsal fixation findings in
      Caucasians, focusing on the lateral rectus capsulopalpebral fascia (lrCPF),
      lateral canthal band (LCB), and the tarsus. MATERIALS AND METHODS: Seven
      Caucasian cadavers (13 eyelids: 7 right and 6 left; age range, 78-101 years) were
      used. Microscopic axial sections parallel to the eyelid margin were made and
      stained with Masson's trichrome. The first and second sections of the upper
      eyelids were obtained at 1 mm and 5 mm, respectively, superior to the upper
      eyelid margin. The first and second sections of the lower eyelid were obtained at
      1 mm and 3 mm, respectively, below the lower eyelid margin. RESULTS: All first
      sections of the upper eyelids (7 specimens: 3 right and 4 left) showed continuity
      of the lrCPF with the tarsus. The LCB merged with the lrCPF and connected to the
      tarsus (3 eyelids) or the muscle of Riolan (4 eyelids). All second sections of
      the upper eyelids (9 specimens: 4 right and 5 left) showed direct communication
      of the lrCPF, intermingling with the LCB, with the tarsus. All first sections of
      the lower eyelids (4 specimens: 2 right and 2 left), showed direct insertions of
      the lrCPF on the tarsus. The LCB, merging with the lrCPF, communicated with the
      tarsus and the muscle of Riolan (all 4 eyelids). All second sections of the lower
      eyelids (7 specimens: 2 right and 5 left) showed direct insertion of the lrCPF,
      intermingling with the LCB, on the tarsus. CONCLUSIONS: The lateral aspect of the
      tarsal plate in Caucasians is supported by the lrCPF and the LCB, similar to that
      in Asians.

PMID- 20683373
TI  - Orbital augmentation with injectable calcium hydroxylapatite for correction of
      postenucleation/evisceration socket syndrome.
AB  - PURPOSE: To demonstrate the utility of injectable calcium hydroxylapatite
      (Radiesse) for orbital volume augmentation to correct
      postenucleation/evisceration socket syndrome (PESS). METHODS: A retrospective
      chart review of all consecutive patients in our practice who received injectable
      calcium hydroxylapatite placed in the extraconal space to augment orbital volume
      was conducted. Patients with at least 6 months follow-up were included in the
      study. RESULTS: Among 26 patients with PESS who received injectable calcium
      hydroxylapatite for orbital volume augmentation, 15 individuals were identified
      with adequate follow-up. The mean amount of preoperative relative enophthalmos
      measured by Hertel exophthalmometry was 4 mm (range 0.5-7 mm). An average
      reduction of 2.4 mm of enophthalmos per syringe of filler was achieved. The mean
      follow-up obtained was 46 weeks (range 24-78 weeks). Most patients demonstrated
      clinical and aesthetic improvement that was observed to continue up to 1.5 years.
      Complications observed included anterior migration of filler, a peribulbar
      hemorrhage, and orbital discomfort. Two patients demonstrated little response to
      filler. CONCLUSIONS: Injectable calcium hydroxylapatite provides a novel, safe,
      simple, cost-effective technique to treat volume deficiency in the anophthalmic
      orbit. Augmentation achieved with this semipermanent filler has demonstrated a
      lasting effect in the orbit with little volume loss. Volume replacement can be
      titrated to the socket requirements. Correction of PESS using this technique may
      be limited in orbits that demonstrate significant fibrosis as a result of
      multiple surgeries, severe trauma, or radiation treatment.

PMID- 20683374
TI  - Deep penetrating orbitocerebral steel spring injury with minimal sequelae: a case
      report.
AB  - The authors report a penetrating orbitocerebral steel mattress spring injury
      without permanent ophthalmic or neurologic sequelae. A 44-year-old female
      mattress factory worker sustained an injury to her right orbit by a high-velocity
      projectile foreign body. Imaging revealed a metallic spring in the right orbit
      traversing the optic nerve and superior orbital fissure and lodging in the
      temporal lobe of the brain. Cerebral angiography demonstrated the steel coil
      around, but not damaging, the middle cerebral artery and other vessels. With a
      combined craniotomy and frontal orbitotomy, the spring was removed by meticulous
      counterclockwise rotation. Postoperatively, the patient had mild left-sided
      weakness that resolved after several weeks. Ocular examination was normal,
      including full extraocular movements and a visual acuity of 20/20 in each eye.
      The authors theorize that the spiral shape and on-axis rotational movement
      allowed the projectile to follow a path of least resistance penetrating deeply
      and coiling around, but not injuring, vital structures. Careful counterclockwise
      rotation under direct intracranial and intraorbital visualization was effective
      in removing the spring.

PMID- 20683375
TI  - Orbital lymphoma presenting with choroidal detachments.
AB  - This report describes a case of orbital B-cell lymphoma of extranodal marginal
      cell type with atypical clinical and radiographic features. This patient
      presented with choroidal effusion and optic disk swelling of the right eye. A CT
      scan revealed an intraconal mass surrounding the optic nerve and indenting the
      globe. A right orbitotomy with biopsy of the mass was performed. Histologic and
      immunohistochemical analysis confirmed a diagnosis of extranodal marginal zone B
      cell lymphoma. This is the first case of primary orbital lymphoma presenting with
      choroidal effusion described in the literature.

PMID- 20683376
TI  - Brow motility in mitochondrial myopathy.
AB  - PURPOSE: To quantify the range of brow excursion in patients with mitochondrial
      myopathy and chronic progressive external ophthalmoplegia (CPEO). METHODS:
      Comparative case series. Digital image processing techniques were used to
      quantify the upper eyelid resting position, brow excursion, and monocular eye
      movements (ductions) in 19 patients with mitochondrial myopathy and CPEO and in
      27 healthy control subjects. RESULTS: All patients with CPEO had ptosis ranging
      from 0.6 to 8 mm. For most patients, eye motility limitation was symmetrical.
      Elevation was the most affected eye movement. Patient's brow motility was on
      average 56.7% of the motility seen in the control group, and did not correlate
      with age or eye motility in any direction. Seventy-six percent of the brows
      displayed more than 2 mm of excursion. CONCLUSIONS: In patients with CPEO, the
      occipitofrontalis muscle is less affected than the extraocular muscles. Most
      patients display a useful degree of brow excursion that theoretically can be used
      to clear the visual axis after a conservative brow suspension.

PMID- 20683377
TI  - Long-term sequelae of childhood bacterial meningitis: an underappreciated
      problem.
AB  - BACKGROUND: Numerous sequelae have been noted in survivors of bacterial
      meningitis; however, few studies document sequelae for several years following a
      childhood episode of bacterial meningitis. In addition, studies generally focus
      on the more commonly found sequelae. To review the known information and
      highlight this gap, this article presents a comprehensive literature review of
      the long-term (>= 5 years of follow-up) sequelae of childhood bacterial
      meningitis. METHODS: A systematic literature search was conducted between
      December 2009 and February 2010. English-language articles published between
      January 1970 and January 2010 were selected for screening. Articles were included
      if the subjects were between the ages of 1 month and <18 years at the time of
      diagnoses of meningitis. RESULTS: A total of 1433 children who were survivors of
      childhood bacterial meningitis were evaluated for sequelae after the time of
      discharge. Of these children, 705 (49.2%) were reported to have 1 or more long
      term sequelae. A majority of reported sequelae were behavioral and/or
      intellectual disorders (n 455, 45.0%). Hearing changes accounted for 6.7% (n 68)
      of sequelae and gross neurologic deficits accounted for 14.3% (n 145).
      DISCUSSION: A majority of childhood bacterial meningitis survivors with long-term
      sequelae that are documented in the literature have academic and behavioral
      limitations. While neurologic deficits may resolve over time, subtle behavioral
      deficits may not be appreciated initially and may continue to affect survivors
      for many years. Further studies are needed to quantify the true societal and
      economic burden of long-term sequelae as well as fully understand the breadth of
      types of sequelae that survivors experience.

PMID- 20683378
TI  - Spectral domain optical coherence tomography in adult-onset vitelliform macular
      dystrophy with cuticular drusen.
AB  - PURPOSE: The purpose of this study was to investigate morphologic differences in
      a consecutive case series of patients suffering from adult-onset vitelliform
      macular dystrophy with cuticular drusen (CD) compared with another patient group
      with a vitelliform lesion only using high-resolution in vivo retinal imaging.
      METHODS: Simultaneous spectral domain optical coherence tomography (870 nm,
      40.000 A-scans per second) and confocal scanning laser ophthalmoscopy were
      performed in 6 patients (12 eyes) with adult-onset vitelliform macular dystrophy
      using a combined instrument (Spectralis HRA+OCT; Heidelberg Engineering,
      Heidelberg, Germany). RESULTS: Mean age was 69 years (59-82 years), and mean
      visual acuity was 20/80. The vitelliform lesion presented with an accumulation of
      yellow-gray material with increased fundus autofluorescence. Spectral domain
      optical coherence tomography imaging showed that the neurosensory detachment was
      filled with an amorphous homogenously reflective material located between the
      retinal pigment epithelium and neurosensory retina in the inferior part of the
      lesion with the superior part being optically empty. The retinal pigment
      epithelium basal membrane/Bruch membrane band on spectral domain optical
      coherence tomography showed multiple focal nodules, in analogy to histologic
      descriptions of CD. Longitudinal observations in a subgroup of patients showed
      that the vitelliform detachment collapsed with subsequent development of
      geographic atrophy in patients with CDs. CONCLUSION: Cuticular drusen may be an
      indicator for a generalized retinal pigment epithelium dysfunction. High
      resolution spectral domain optical coherence tomography allows to image
      morphologic differences in adult-onset vitelliform macular dystrophy with and
      without CDs, providing further evidence that adult-onset vitelliform macular
      dystrophy with CDs represents a separate disease entity.

PMID- 20683379
TI  - Retinal thickness and volume measurements in diabetic macular edema: a comparison
      of four optical coherence tomography systems.
AB  - PURPOSE: To compare different spectral domain optical coherence tomography
      devices regarding retinal thickness values in patients with diabetic macular
      edema and to correlate the results with conventional time domain Stratus OCT
      data. METHODS: Thirty eyes of 30 consecutive patients with diabetic macular edema
      were included into a prospective study. The macula was examined by Spectralis
      HRA+OCT, Cirrus HD-OCT, 3D OCT-1000, and Stratus OCT. The procedures' sequence
      was performed by a single experienced technician in a randomized fashion
      according to a computer-generated list. In each eye, foveal thickness, foveal
      volume, and total macular volume were measured automatically. Intraclass
      correlation, coefficients of variance, and coefficients of repeatability were
      calculated. RESULTS: Foveal thickness differed between the particular devices
      with a mean +/- SD ranging from 359.97 +/- 105.84 MUm to 437.70 +/- 115.84 MUm.
      Correlation between the different OCT devices resulted in r > 0.7 (Pearson), and
      intraclass correlation was >0.9. Agreement of measurements was assessed showing a
      mean difference of foveal thickness values ranging from 19.2 MUm to 77.7 MUm (P <
      0.05) and coefficients of repeatability ranging from 37.7 MUm to 87.4 MUm.
      CONCLUSION: While intradevice reproducibility is satisfactory, retinal thickness
      and volume measurements should not be used interchangeably because measurements
      differed significantly between systems. The lack of interdevice agreement seems
      to be related to the different segmentation algorithm of thickness measurement
      and should be considered because it may strongly influence treatment decisions
      and conclusions.

PMID- 20683380
TI  - Dosing regimen and the frequency of macular hemorrhages in neovascular age
      related macular degeneration treated with ranibizumab.
AB  - PURPOSE: The purpose of this study was to investigate if monthly intravitreal
      ranibizumab decreases risk of macular hemorrhages in patients with choroidal
      neovascularization secondary to age-related macular degeneration. METHODS:
      Incidences of macular hemorrhages in the control and ranibizumab groups from
      three, multicenter, randomized, clinical trials (MARINA, ANCHOR, and PIER) were
      compared. Two time intervals (Months 0-3 and 5-17) were evaluated to account for
      transition from monthly to quarterly injections in PIER. Time interval after
      Month 17 was excluded because of crossover from control to active treatment in
      all trials. RESULTS: Months 0-3: All trials showed higher incidence rates of
      hemorrhages in control compared with ranibizumab groups (ANCHOR: photodynamic
      therapy [27.3%], 0.3 mg [8.0%], 0.5 mg [8.6%]; MARINA: sham [18.6%], 0.3 mg
      [8.8%], 0.5 mg [8.8%]; and PIER: sham [16.1%], 0.3 mg [3.4%], 0.5 mg [3.3%]). In
      ANCHOR and MARINA, data of Months 5-17 showed higher incidence rates in control
      compared with monthly ranibizumab groups (ANCHOR: photodynamic therapy [47.8%],
      0.3 mg [12.5%], 0.5 mg [12.3%]; and MARINA: sham [38.0%], 0.3 mg [13.2%], 0.5 mg
      [13.0%]), but this was not seen for quarterly ranibizumab groups in PIER (sham
      [22.4%], 0.3 mg [23.7%], 0.5 mg [28.3%]). CONCLUSION: Treatment with monthly
      intravitreal ranibizumab was associated with reduced risk of new macular
      hemorrhages when compared with photodynamic therapy (ANCHOR) or sham (MARINA and
      PIER). There was no difference between PIER quarterly ranibizumab-treated and
      sham patients.

PMID- 20683382
TI  - Diagnostic and therapeutic challenges.

PMID- 20683383
TI  - Autofusion in the immature spine treated with growing rods.
AB  - STUDY DESIGN: Retrospective case review of skeletally immature patients treated
      with growing rods. Patients received an average of 9.6 years follow-up care.
      OBJECTIVE: (1) to identify the rate of autofusion in the growing spine with the
      use of growing rods; (2) to quantify how much correction can be attained with
      definitive instrumented fusion after long-term treatment with growing rods; and
      (3) to describe the extent of Smith-Petersen osteotomies required to gain
      correction of an autofused spine following growing rod treatment. SUMMARY OF
      BACKGROUND DATA: The safety and use of growing rods for curve correction and
      maintenance in the growing spine population has been established in published
      reports. While autofusion has been reported, the prevalence and sequelae are not
      known. METHODS: Nine skeletally immature children with scoliosis were identified
      who had been treated using growing rods. A retrospective review of the medical
      records and radiographs was conducted and the following data collected:
      complications, pre- and postoperative Cobb angles at time of initial surgery
      (growing rod placement), pre- and postoperative Cobb angles at time of final
      surgery (growing rod removal and definitive fusion), total spine length as
      measured from T1-S1, % correction since initiation of treatment and at definitive
      fusion, total number of surgeries, and number of patients found to have
      autofusion at the time of device removal. RESULTS: The rate of autofusion in
      children treated with growing rods was 89%. The average percent of the Cobb angle
      correction obtained at definitive fusion was 44%. On average, 7 osteotomies per
      patient were required at the time of definitive fusion due to autofusion.
      CONCLUSION: Although growing rods have efficacy in the control of deformity
      within the growing spine, they also have adverse effects on the spine. Immature
      spines treated with a growing rod have high rates of unintended autofusion which
      can possibly lead to difficult and only moderate correction at the time of
      definitive fusion.

PMID- 20683384
TI  - In vivo three-dimensional kinematics of the cervical spine during head rotation
      in patients with cervical spondylosis.
AB  - STUDY DESIGN: Kinematics of the cervical spine during head rotation was
      investigated using 3-dimensional (3D) magnetic resonance imaging (MRI) in
      patients with cervical spondylosis (CS). OBJECTIVE: To demonstrate in vivo 3D
      kinematics of the spondylotic cervical spine during head rotation. SUMMARY OF
      BACKGROUND DATA: Several in vivo studies have identified kinematic differences
      between normal and spondylotic subjects, but only two-dimensional
      flexion/extension motion has been investigated. Differences of in vivo 3D
      cervical motion during head rotation between normal and spondylotic subjects have
      yet to be clarified. METHODS: Ten healthy volunteers (control group) and 15
      patients with CS (CS group) underwent 3D MRI of the cervical spine with the head
      rotated to 5 positions (neutral, +/-45 degrees  and +/-maximal head rotation).
      Relative motions of the cervical spine were calculated by automatically
      superimposing a segmented 3D MRI of the vertebra in the neutral position over
      images for each position using volume registration. The 3D motions of adjacent
      vertebra were represented with 6 degrees of freedom by Euler angles and
      translations on the coordinate system. RESULTS: Compared with the control group,
      the CS group showed significantly decreased mean axial rotation and mean coupled
      lateral bending at C5-C6 and C6-C7 and significantly increased mean coupled
      lateral bending at C2-C3 and C3-C4, although both the groups showed the same
      pattern of coupled motions. CONCLUSION: The in vivo 3D kinematics of the
      spondylotic cervical spine during head rotation was accurately depicted and
      compared with those of healthy cervical spines for the first time.

PMID- 20683385
TI  - Risk-benefit assessment of surgery for adult scoliosis: an analysis based on
      patient age.
AB  - STUDY DESIGN: Retrospective review of a prospective, multicenter database.
      OBJECTIVE: The purpose of this study was to assess whether elderly patients
      undergoing scoliosis surgery had an incidence of complications and improvement in
      outcome measures comparable with younger patients. SUMMARY OF BACKGROUND DATA:
      Complications increase with age for adults undergoing scoliosis surgery, but
      whether this impacts the outcomes of older patients is largely unknown. METHODS:
      This is a retrospective review of a prospective, multicenter spinal deformity
      database. Patients complete the Oswestry Disability Index (ODI), SF-12, Scoliosis
      Research Society-22 (SRS-22), and numerical rating scale (NRS; 0-10) for back and
      leg pain. Inclusion criteria included age 25 to 85 years, scoliosis (Cobb >= 30
      degrees ), plan for scoliosis surgery, and 2-year follow-up. RESULTS: Two hundred
      six of 453 patients (45%) completed 2-year follow-up, which is distributed among
      age groups as follows: 25 to 44 (n = 47), 45 to 64 (n = 121), and 65 to 85 (n =
      38) years. The percentages of patients with 2-year follow-up by age group were as
      follows: 25 to 44 (45%), 45 to 64 (48%), and 65 to 85 (40%) years. These groups
      had perioperative complication rates of 17%, 42%, and 71%, respectively (P <
      0.001). At baseline, elderly patients (65-85 years) had greater disability (ODI,
      P = 0.001), worse health status (SF-12 physical component score (PCS), P <
      0.001), and more severe back and leg pain (NRS, P = 0.04 and P = 0.01,
      respectively) than younger patients. Mean SRS-22 did not differ significantly at
      baseline. Within each age group, at 2-year follow-up there were significant
      improvements in ODI (P <= 0.004), SRS-22 (P <= 0.001), back pain (P < 0.001), and
      leg pain (P <= 0.04). SF-12 PCS did not improve significantly for patients aged
      25 to 44 years but did among those aged 45 to 64 (P < 0.001) and 65 to 85 years
      (P = 0.001). Improvement in ODI and leg pain NRS were significantly greater among
      elderly patients (P = 0.003, P = 0.02, respectively), and there were trends for
      greater improvements in SF-12 PCS (P = 0.07), SRS-22 (P = 0.048), and back pain
      NRS (P = 0.06) among elderly patients, when compared with younger patients.
      CONCLUSION: Collectively, these data demonstrate the potential benefits of
      surgical treatment for adult scoliosis and suggest that the elderly, despite
      facing the greatest risk of complications, may stand to gain a disproportionately
      greater improvement in disability and pain with surgery.

PMID- 20683386
TI  - Risk factors for major complications after surgery for neuromuscular scoliosis.
AB  - STUDY DESIGN: Retrospective, case series. OBJECTIVE: To determine the prevalence
      of major complications and to identify factors that increase the risk of
      complications in patients undergoing surgery for neuromuscular scoliosis. SUMMARY
      OF BACKGROUND DATA: Complications after surgery for neuromuscular scoliosis are
      more prevalent than in idiopathic scoliosis. However, the associated risk factors
      have not been statistically significant. METHODS: Our computerized Pediatric
      Orthopedic Spine Database identified 131 consecutive patients with neuromuscular
      scoliosis, excluding those with myelodysplasia, who underwent surgery and had a
      minimum of 2 years of follow-up. Preoperative, intraoperative, and postoperative
      factors were analyzed for any association with major complications and length of
      stay using stepwise logistic and multiple regression analyses. Odds ratios were
      calculated for significant dichotomous variables, and receiver operator
      characteristic curves were created for significant continuous variables. RESULTS:
      There were 81 male and 50 female patients with a mean age at surgery of 13.4
      years (range, 6-21 years). The majority of patients (n = 75) had cerebral palsy.
      Eighty-eight patients (67%) underwent posterior spinal fusion and segmental
      spinal instrumentation (only), whereas 43 patients (33%) underwent an anterior
      spinal fusion followed by a posterior spinal fusion with segmental spinal
      instrumentation. Seventy-seven patients (59%) were fused to the pelvis using the
      Galveston technique. The mean follow-up was 3.9 years (range, 2-16.9 years).
      There were 46 major complications in 37 patients (28% prevalence), including 2
      deaths.Nonambulatory status (P < 0.05) and preoperative curve magnitude (P <
      0.01) were associated with an increased prevalence of major complications.
      Nonambulatory patients (n = 94) were almost 4 times more likely to have a major
      complication (odds ratio of 3.8, P < 0.05) in comparison with ambulatory
      patients. A preoperative major curve magnitude of >= 60 degrees  (P < 0.01) was
      the most accurate indicator for an increased risk for a major complication.
      CONCLUSION: Nonambulatory status and a preoperative curve magnitude (>= 60
      degrees ) are directly associated with an increased risk for major complications
      and indirectly associated with increased length of stay. As such, we recommend
      operative intervention in neuromuscular scoliosis before curve progression to >=
      60 degrees . Level of Evidence. Level III.

PMID- 20683387
TI  - The effect of a new anular repair after discectomy in intervertebral disc
      degeneration: an experimental study using a porcine spine model.
AB  - STUDY DESIGN: In vitro and in vivo studies to assess the effect of direct anular
      repair on subsequent degeneration of intervertebral discs (IVDs). OBJECTIVE: To
      assess whether a new suturing method could provide sealing effect on IVD after
      discectomy, and influence degenerative process of IVD. SUMMARY OF BACKGROUND
      DATA: Recurrent disc herniation and subsequent disc degeneration are major
      problems after discectomy. Anular repair can reduce the risk of recurrence, but
      its effect on disc degeneration needs more investigation. METHODS: A new suturing
      technique, the modified purse-string suture (MPSS), was designed for direct
      closure of anular incision. Intact motion segments of porcine lumbar spine were
      used to validate this technique in resisting disc pressure under mechanical
      loadings. A transverse slit incision was made in the anterior anulus of porcine
      cervical discs, with or without sealing of the anular defect by this suturing
      method. Magnetic resonance imaging grading was recorded before and after surgery.
      Anular healing was assessed histologically and gene expression of aggrecan,
      collagen type I, II, and matrix metalloproteinase-13 in nucleus pulposus were
      investigated. RESULTS: The average failure force of axial compression was 1150.3
      +/- 121.1 N for a simple suture, and 2917.9 +/- 627.6 N for a MPSS. Cyclic
      loading test showed that the repaired discs succeeded against repeated
      compression forces. Magnetic resonance imaging and gross appearances showed
      lesser degenerative changes in repaired discs than in injured discs at each time
      period. In repaired discs, mRNA expression of aggrecan and type II collagen
      downregulated slightly with time, whereas it decreased rapidly and persistently
      in unrepaired discs. Histologic findings showed primary healing of outer anular
      tract in repaired discs. CONCLUSION: In this pilot study, the MPSS can provide
      effectively sealing for damaged anulus to withstand stresses. Direct repair of
      anular incision by this suturing method does significantly slow down degenerative
      process within discs after discectomy.

PMID- 20683388
TI  - Mechanical function of vertebral body osteophytes, as revealed by experiments on
      cadaveric spines.
AB  - STUDY DESIGN: Mechanical testing of cadaveric spines. OBJECTIVE: To determine
      whether vertebral body osteophytes act primarily to reduce compressive stress on
      the intervertebral discs, or to stabilize the spine in bending. SUMMARY OF
      BACKGROUND DATA: The mechanical significance of vertebral osteophytes is unclear.
      METHODS: Thoracolumbar spines were obtained from cadavers, aged 51 to 92 years,
      with vertebral body osteophytes, mostly anterolateral. Twenty motion segments,
      from T5-T6 to L3-L4, were loaded in compression to 1.5 kN, and then in flexion,
      extension, and lateral bending to 10 to 25 Nm (depending on specimen size) with a
      compressive preload. Vertebral movements were tracked using an optical 2
      dimensional MacReflex system. Tests were performed in random order, and were
      repeated after excision of all osteophytes. Osteophyte function was inferred from
      (a) changes in the force or moment resisted and (b) changes in tangent stiffness,
      measured at maximum displacement or rotation angle. Volumetric bone mineral
      density (BMD) was measured using dual photon x-ray absorptiometry and water
      immersion. Results were analyzed using repeated measures analysis of variance.
      RESULTS: Resistance to compression was reduced by an average of 17% after
      osteophyte removal (P < 0.05), and resistance to bending moment in flexion,
      extension, and left and right lateral bending was reduced by 49%, 36%, 36%, and
      35%, respectively (all P < 0.01). Changes in tangent stiffness were similar.
      Osteophyte removal increased the neutral zone in bending (P < 0.05) and, on
      average, reduced motion segment BMD by 7% to 9%. Results were insensitive to
      applied loads and moments, but several changes were proportional to osteophyte
      size. CONCLUSION: Vertebral body osteophytes resist bending movements more than
      compression. Because they reverse the instability in bending that can stimulate
      their formation, these osteophytes seem to be adaptive rather than degenerative.
      Results suggest that osteophytes could cause clinical BMD measurements to
      underestimate vertebral compressive strength.

PMID- 20683389
TI  - Chemistry, pharmacology, and metabolism of emerging drugs of abuse.
AB  - In recent years, besides the classic designer drugs of the amphetamine type, a
      series of new drug classes appeared on the illicit drugs market. The chemistry,
      pharmacology, toxicology, metabolism, and toxicokinetics is discussed of 2,5
      dimethoxy amphetamines, 2,5-dimethoxy phenethylamines, beta-keto-amphetamines,
      phencyclidine derivatives as well as of herbal drugs, ie, Kratom. They have
      gained popularity and notoriety as rave drugs. The metabolic pathways, the
      involvement of cytochrome P450 isoenzymes in the main pathways, and their roles
      in hepatic clearance are also summarized.

PMID- 20683390
TI  - Overview of sotrastaurin clinical pharmacokinetics.
AB  - Sotrastaurin (AEB071) is an investigational immunosuppressant that blocks T
      lymphocyte activation through protein kinase C inhibition. It is currently in
      Phase II of clinical development for the prevention of acute rejection after
      solid organ transplantation. In renal transplant clinical trials, sotrastaurin
      has been administered at doses of 200 to 300 mg twice daily. Using a validated
      liquid chromatography method with tandem mass spectrometry, steady-state predose
      blood concentrations averaged approximately 600 and 900 ng/mL at these dose
      levels, respectively. Sotrastaurin is primarily metabolized through CYP3A4. There
      is one active metabolite, N-desmethyl-sotrastaurin, that is present at low blood
      concentrations (less than 5% of the parent exposure). The elimination half-life
      of sotrastaurin averages 6 hours. Clinical drug interaction studies to date have
      demonstrated that sotrastaurin increases the area under the concentration-time
      curve of everolimus 1.2-fold and of tacrolimus twofold. Conversely, sotrastaurin
      area under the concentration-time curve is increased up to 1.8-fold by
      cyclosporine and 4.6-fold by ketoconazole. Blood samples from renal transplant
      patients receiving sotrastaurin were stimulated ex vivo by protein kinase C
      dependent pathways. Inhibition of cytokine production, expression of CD69, and
      thymidine uptake served as biomarkers that demonstrated the ability of
      sotrastaurin to inhibit T-cell activation and proliferation at the doses used in
      these studies. Phase II trials have paired sotrastaurin with tacrolimus,
      mycophenolic acid, or everolimus. The clinical and pharmacokinetic results of
      these and upcoming trials will determine the optimal immunosuppressive regimen to
      benefit from sotrastaurin's novel mechanism of action and whether therapeutic
      drug monitoring will be beneficial.

PMID- 20683391
TI  - Validation of sparse sampling strategies to estimate cyclosporine A area under
      the concentration-time curve using either a specific radioimmunoassay or high
      performance liquid chromatography method.
AB  - INTRODUCTION: Area under the concentration-time curve (AUC) has been advocated as
      a better parameter to monitor cyclosporine A than trough concentrations. Up to
      now, more than 100 equations to estimate AUC using a limited sampling strategy
      have been published, but not all have been validated. MATERIAL AND METHODS: Eight
      equations for AUC0-12h and two for AUC0-8h were validated. Concentrations of
      cyclosporine A were analyzed by high-performance liquid chromatography (HPLC) and
      a specific radioimmunoassay (RIA) method. Forty male renal transplant patients
      were included in the study. Blood samples were taken predose and at 0.5, 1, 1.5,
      2, 3, 5, 8, and 12 hours after the morning dose when the patient was in steady
      state. The percentage prediction error (%pe) was used for an assessment of the
      performance of the equations. Mean %pe less than +/- 15% and absolute %pe less
      than 30% in 95% of predictions were considered to be acceptable. Other
      possibilities such as %pe less than 25%, 20%, and 15% were also tested. RESULTS:
      Eight equations for AUC0-12h met the requirements using both assays, six in the
      HPLC set only and four in the RIA set only. The highest precision was obtained
      with AUC0-12h = 123.792 + 1.165*C1h + 3.021*C3h + 7.33*C8h proposed by de Mattos
      et al. The mean %pe was 1% +/- 8% (-16 to 19) for HPLC (values given as mean +/-
      standard deviation [range]) and -1 +/- 5 (-17 to 10) for RIA. Mean absolute %pe
      was 7 +/- 5 (0.0 to 19) for HPLC and 4 +/- 4 (0.0 to 17) for RIA. For clinical
      use, the most suitable equation was AUC0-12h = 363.078 + 8.77*C1h + 3.07*C3h
      proposed by Wacke et al, which produced the second lowest %pe and used two
      sampling points in the period of 1 to 3 hours after dose. The mean %pe was -7 +/-
      10 (-25 to 25) for HPLC and 2.3 +/- 6 (-10 to 17) for RIA. Mean absolute %pe was
      10 +/- 7 (0.4 to 25) for HPLC and 5 +/- 4 (0.0 to 17) for RIA. The equation: AUC0
      8h = 55.37 + 2.89*C0h + 1.08*C1h0.9*C2h + 2.23*C3h proposed by Foradori et al met
      the criteria with 95% of prediction with absolute %pe less than 15% in the HPLC
      set and 10% in the RIA set. CONCLUSION: The validation of equations is of major
      importance for prediction precision, whereas the analytical method for limited
      sampling strategy proposals had no influence. Because of the wide interassay
      variability, it is also important to know which analytical method was used for
      AUC calculation when interpreting the results.

PMID- 20683392
TI  - Fast liquid chromatography-tandem mass spectrometry method for routine assessment
      of irinotecan metabolic phenotype.
AB  - Irinotecan (CPT-11) is an anticancer drug with a complex in vivo metabolism
      widely used in the treatment of colon cancer. The assessment of the CPT-11
      metabolic phenotype is an important clinical component for personalizing the
      administered dose. In this study, we report the development of a rapid and
      sensitive liquid chromatography-tandem mass spectroscopy method for the
      simultaneous quantitation of CPT-11 and its major metabolites generated by
      hydrolysis (SN-38, active metabolite) or through oxidative (NPC and APC) and
      glucuronidation (SN-38G) pathways. The method used a small volume of plasma and
      is based on simple protein plasma precipitation with two volumes of acetonitrile
      containing camptothecine as an internal standard. Analytes extracted in the
      supernatant fraction were converted to the lactone form and further separated by
      an acetonitrile gradient on a Kinetex C18 (50 * 2 mm) column in the presence of
      0.01% formic acid. The quantitative measurement was performed by an API
      4000/Qtrap operating in the triple-quadruple mode. The Multiple Reaction
      Monitoring transitions were: m/z 587->167 for CPT-11, m/z 393->349 for SN-38, m/z
      619->393 for APC, m/z 519->393 for NPC, and m/z 569->393 for SN-38G. The mean
      overall recovery in plasma was in the range of 78% to 86% with a low matrix
      suppression effect (9.0% or less). The lower limit of quantitation was 0.2 ng/mL
      for NPC and SN-38 and 0.5 ng/mL for SN-38G, APC, and CPT-11. Linearity was
      checked up to 2000 ng/mL, whereas the intra- and interday accuracy and precision
      for both the parent drug and its metabolites was -3.7% to 13.8% and 3.7% to
      13.1%, respectively. The method proved to be robust and suitable for therapeutic
      drug monitoring as well as for pharmacogenetic-pharmacokinetic correlation
      studies.

PMID- 20683393
TI  - Current status of therapeutic drug monitoring in Australia and New Zealand: a
      need for improved assay evaluation, best practice guidelines, and professional
      development.
AB  - The measurement of drug concentrations, for clinical purposes, occurs in many
      diagnostic laboratories throughout Australia and New Zealand. However, the
      provision of a comprehensive therapeutic drug monitoring (TDM) service requires
      the additional elements of pre- and postanalytical advice to ensure that
      concentrations reported are meaningful, interpretable, and clinically applicable
      to the individual patient. The aim of this project was to assess the status of
      TDM services in Australia and New Zealand. A range of professions involved in key
      aspects of TDM was surveyed by questionnaire in late 2007. Information gathered
      included: the list of drugs assayed; analytical methods used; interpretation
      services offered; interpretative methods used; and further monitoring advice
      provided. Fifty-seven responses were received, of which 42% were from hospitals
      (public and/or private); 11% a hospital (public and/or private) and pathology
      provider; and 47% a pathology provider only (public and/or private). Results
      showed that TDM is applied to a large number of different drugs. Poorly
      performing assay methods were used in some cases, even when published guidelines
      recommended alternative practices. Although there was a wide array of assays
      available, the evidence suggested a need for better selection of assay methods.
      In addition, only limited advice and/or interpretation of results was offered. Of
      concern, less than 50% of those providing advice on aminoglycoside dosing in
      adults used pharmacokinetic tools with six of 37 (16.2%) respondents using
      Bayesian pharmacokinetic tools, the method recommended in the Australian
      Therapeutic Guidelines: Antibiotic. In conclusion, the survey highlighted
      deficiencies in the provision of TDM services, in particular assay method
      selection and both quality and quantity of postanalytical advice. A range of
      recommendations, some of which may have international implications, are
      discussed. There is a need to include measures of impact on clinical decision
      making when assessing assay methodologies. Best practice guidelines and
      professional standards of practice in TDM are needed, supported by an active
      program of professional development to ensure the benefits of TDM are realized.
      This will require significant partnerships between the various professions
      involved.

PMID- 20683395
TI  - Human telomerase RNA gene amplification detection increases the specificity of
      cervical intraepithelial neoplasia screening.
AB  - OBJECTIVES: The purpose of this study was to evaluate the clinical significance
      of genomic amplification of the human telomerase RNA gene (TERC) for cervical
      cancer screening and explore whether it can serve as a biomarker to improve the
      specificity of human papillomavirus (HPV) DNA testing for cervical cancer
      screening. METHODS: One hundred twenty women, including 20 cases of normal
      (control), 14 cases of cervical intraepithelial neoplasia grade I (CIN I), 35
      cases of CIN II, 36 cases of CIN III, and 15 cases of squamous cervical cancer
      diagnosed by histopathologic evaluation, were subjected to cytopathologic
      examination, TERC detection by fluorescence in situ hybridization (FISH), and HPV
      DNA testing by Hybrid Capture II. RESULTS: TERC amplification was significantly
      associated with cytopathologic diagnosis (P < 0.001) and histopathologic
      evaluation (P < 0.001). The positive rate of TERC gain was significantly higher
      in patients with CIN III or squamous cervical cancer than in patients with CIN I
      or those in the control group (P < 0.001). The specificity and positive
      predictive value of FISH for detecting CIN II or more severe cervical lesions (>
      or = CIN II) were obviously higher than those of HPV DNA testing (97.1% vs 52.9%,
      98.7% vs 83.8%). CONCLUSIONS: TERC amplification analyzed by FISH may serve as an
      adjunctive test to HPV DNA testing for improving the specificity and positive
      predictive value of cervical cancer screening.

PMID- 20683396
TI  - Chemotherapy induces macrophage chemoattractant protein-1 production in ovarian
      cancer.
AB  - OBJECTIVES: Tumor infiltrating macrophages play an important role in tumor
      progression. Macrophage chemoattractant protein-1 (MCP-1) is one of the major
      chemokines responsible for inducing macrophage migration. Our objective was to
      investigate chemotherapy-induced modulation of MCP-1 in ovarian cancer by
      investigating macrophage infiltration, tumor vascularity, and MCP-1 expression
      after chemotherapy exposure. METHODS: MA-148 ovarian cancer cells were treated
      with paclitaxel (43 pg/mL) and carboplatin (5 microg/mL) alone or in combination.
      Reverse transcription-polymerase chain reaction determined MCP-1 transcript
      levels and enzyme-linked immunosorbent assay evaluated MCP-1 protein production
      at multiple time points. The effect of kinase inhibitors on MCP-1 expression was
      investigated. In vivo MCP-1 production was examined in tumor-bearing mice and
      immunohistochemistry with fluorescein isothiocyanate conjugated anti-mouse F4/80
      antibody, phycoerythrin-anti-CD31, and terminal deoxynucleotide transferase dUTP
      nick-end labeling assay were performed. RESULTS: Macrophage chemoattractant
      protein-1 transcript levels were up-regulated in MA-148 after treatment with
      paclitaxel and carboplatin individually and in combination. The greatest
      elevation was seen with combination therapy: 2.5-fold increase in the MCP-1
      protein levels from baseline (P = 0.011) with the mitogen-activated protein
      kinase and janus kinases/signal transducers and activators of transcription
      pathways appearing to be involved in the regulation of MCP-1 production. In vivo
      mouse studies confirmed increased MCP-1 production after chemotherapy; however,
      there was no significant difference in macrophage, apoptosis, or vessel density.
      CONCLUSIONS: Macrophage chemoattractant protein-1 is up-regulated in ovarian
      cancer after chemotherapy in vitro and in vivo. Whether MCP-1 production is
      increased because of a stress-induced response or a scavenger response promoting
      macrophage infiltration remains unknown. Chemotherapy induction of MCP-1 in
      ovarian cancer suggests this chemokine plays an important role in the immune
      response occurring after chemotherapy exposure.

PMID- 20683397
TI  - Pregnancy outcomes after conservative surgical management of ovarian neoplasms
      treated at a single institution.
AB  - HYPOTHESIS: Conservative surgical management of ovarian neoplasms can result in
      favorable oncologic and obstetric outcomes. METHODS: All reproductive-age women
      (18-45 years old) with stage IA to stage IIC ovarian neoplasms (N = 161) were
      retrospectively identified from a single institution's tumor registry between
      1990 and 2007. Operative, pathological, outpatient, and delivery records were
      reviewed to confirm histological findings, stage, extent of surgical resection,
      adjuvant treatment, oncologic outcomes, and pregnancy outcomes. RESULTS: Women
      who underwent conservative surgical management for ovarian neoplasms (n = 61
      [37.9%]) were identified, including those with low malignant potential (LMP, n =
      36), epithelial (n = 12), germ cell (n = 6), and sex cord (n = 7) tumors.
      Thirteen women conceived 23 pregnancies, producing a pregnancy rate of 25.0%
      overall and of 68.4% for those attempting conception. Women with LMP tumors
      conceived most pregnancies and had the highest number of antenatal complications.
      Of those receiving adjuvant chemotherapy (n = 8), 12.5% were able to conceive
      after their treatment and with no reported congenital anomalies. Pregnancy after
      a diagnosis of ovarian neoplasm did not impact disease recurrence (0% vs 7.7%, P
      = 0.56) or survival (100% vs 100%, P = 1.0). CONCLUSIONS: Conservative surgery
      may be an acceptable option for reproductive-age women with early-stage ovarian
      neoplasms. We report pregnancy and oncologic outcomes for a cohort of women
      managed conservatively for LMP, epithelial, germ cell, and sex cord ovarian
      neoplasms.

PMID- 20683398
TI  - Intraperitoneal catheter leads to prolongation of the time to normalization of
      serum CA125 levels.
AB  - OBJECTIVE: The intraperitoneal (IP) catheter has the potential to cause
      peritoneal irritation, which may contribute to an elevated CA125 level. We
      hypothesize that patients undergoing IP chemotherapy may have elevated CA125
      values when compared with patients receiving intravenous (IV) chemotherapy.
      METHODS: From February 2006 to July 2007, optimally debulked patients with stage
      III and stage IV ovarian carcinoma from a single institution were offered an
      outpatient IV/IP chemotherapy regimen modified from Gynecologic Oncology Group
      172. They were matched to a cohort of similar patients who received IV paclitaxel
      and carboplatin. Demographic data and CA125 levels were collected before each
      cycle of chemotherapy and after the removal of the IP catheter. Statistical
      analysis was completed using a chi2 test with a significance level of P < 0.05.
      RESULTS: Fifty patients received the standard IV regimen, and 38 patients
      completed the modified IV/IP regimen. There was no statistical difference in the
      median CA125 values between the 2 groups during the treatment. After 6 cycles of
      therapy, 68.4% (26/38) of the IP cohort had a normal CA125 level before IP
      catheter removal compared with 78% (39/50) in the IV chemotherapy cohort (P =
      0.44). After removal of the IP catheter, 86.8% (33/38) of the patients had a
      normal CA125 value (68.4% vs 86.8%, P = 0.049). CONCLUSIONS: After removal of the
      IP catheter, an additional 18.2% (7/38) of patients in the IP group had
      normalized their CA125 level. Because CA125 levels at the end of the treatment
      have prognostic significance, the role of the IP catheter in an elevated CA125
      level must be considered.

PMID- 20683399
TI  - Clinical utility of positron emission tomography/computed tomography in the
      evaluation of suspected recurrent ovarian cancer in the setting of normal CA-125
      levels.
AB  - OBJECTIVES: This study was conducted to estimate the accuracy of [18F]
      fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT)
      as compared with contrast-enhanced CT (CECT) in detecting cancer in patients who
      have normal cancer antigen (CA)-125 (<35 U/dL) but are suspected of having a
      recurrent disease based on clinical symptoms. METHODS: We retrospectively
      reviewed the records of patients who had undergone primary cytoreductive surgery
      and subsequently underwent CECT and FDG-PET/CT for suspected recurrence. [18F]
      fluorodeoxyglucose positron emission tomography/computed tomography and CECT
      interpretation to evaluate a recurrent disease was carried out independently by 2
      experienced radiologists who were blinded to the final diagnosis for the
      suspected recurrence. Long-term follow-up imaging (12 months) and biopsy reports
      were used to assess the true status of the suspected recurrence seen on FDG
      PET/CT or CECT. Sensitivity and specificity of all modalities were estimated.
      McNemar test was used to compare pairs of modalities. All tests were 2-sided, and
      P < or = 0.05 was considered statistically significant. RESULTS: Sixty-six
      patients met the eligibility criteria for inclusion in our analysis. Fifty-eight
      percent (18/31) and 54% (17/31) of the patients with normal CA-125 levels had
      evidence of a recurrent disease on FDG-PET/CT and CECT, respectively. Thirty-one
      percent (6/19) of the patients with no indication of cancer on CECT had evidence
      of disease on FDG-PET/CT images, which was supported by pathological proof.
      CONCLUSION: [18F]-Fluorodeoxyglucose positron emission tomography/computed
      tomography is capable of detecting ovarian cancer recurrence in symptomatic
      patients with normal CA-125 levels and, in this setting, has slightly better
      sensitivity than CECT and can be considered as the frontline modality for all
      such patients.

PMID- 20683400
TI  - Prognostic relevance of uncommon ovarian histology in women with stage III/IV
      epithelial ovarian cancer.
AB  - BACKGROUND: The prognostic relevance of uncommon epithelial ovarian cancer (EOC)
      histological subtypes remains controversial. The Gynecologic Cancer InterGroup
      (GCIG) initiated this meta-analysis to assess the relative prognosis of women
      with a diagnosis of rare EOC histologies from completed, prospectively randomized
      studies performed by cooperative GCIG study groups. METHODS: Studies eligible for
      analysis included first-line treatment of at least 150 patients with stage III/IV
      EOC treated with a platinum/taxane-based regimen. Collaborating groups were to
      provide patient-level data. Serous acted as the reference histology, and a
      proportional hazards model was used to estimate the relative rate of progression
      or death. RESULTS: Data on 8704 women with stage III/IV EOC from 7 randomized
      trials were included in these analyses. Two hundred twenty-one patients (2.5%)
      had clear cell carcinoma; 264 (3.0%), mucinous; and 36 (0.4%), transitional cell.
      The mean age of patients with serous histology was greater than those with
      mucinous (4.1 years) and clear cell (2.6 years, P < 0.001). Mucinous, clear cell,
      and transitional cell tumors were more likely to be completely resected than
      serous (P < 0.05). When controlling for age and residual disease, mucinous and
      clear cell tumors had shorter times to progression (hazards ratio [HR], 2.1; 95%
      confidence interval [CI], 1.8-2.4 and HR, 1.6; 95% CI, 1.4-1.9, respectively) and
      death (HR, 2.7; 95% CI, 2.3-3.1 and HR, 2.2; 95% CI, 1.8-2.6, respectively)
      compared with serous. The median overall survival for serous, clear cell,
      mucinous, and endometrioid histologies were 40.8, 21.3, 14.6, and 50.9 months.
      CONCLUSIONS: Mucinous and clear cell carcinomas are independent predictors of
      poor prognosis in stage III/IV EOC. Studies targeting these rare histological
      subtypes are warranted and will require significant intergroup collaboration.

PMID- 20683401
TI  - Multicenter phase 2 study of combined gemcitabine and epirubicin as second-line
      treatment for patients with advanced ovarian cancer.
AB  - OBJECTIVE: The aim of this phase 2 trial was to evaluate the tolerability and
      efficacy of combined gemcitabine (G) and epirubicin (E) as second-line treatment
      for patients with advanced ovarian cancer. METHODS: Treatment with G 1000 mg/m2
      (days 1 and 8) and E 60 mg/m2 (day 1) every 3 weeks for 3 or, in the absence of
      progression, 6 courses. RESULTS: Fifty patients with advanced ovarian cancer (31
      serous, 2 endometrioid, 10 unclassified adenocarcinoma, and 7 other) and a median
      age of 60 years (range, 38-74 years) were enrolled after giving their informed
      consent. Performance status according to the Eastern Cooperative Oncology Group
      was 0 in 29 patients (58%), 1 in 17 patients (34%), and 2 in 4 patients (8%), and
      the initial stages according to the International Federation of Gynecology and
      Obstetrics were I to II in 4 patients (8%), III in 31 patients (62%), and IV in
      15 patients (30%). They had previously received a median of 1.5 lines of
      treatment (range, 1-4). The median platinum-free interval was 5 months (range, 0
      12 months): 32 patients had relapse within 6 months and 18 patients had relapse
      after 6 months. The response rate was 42% (2% complete response and 40% partial
      response), with a median duration of 7.2 months: the corresponding figures were
      37.5% and 5.2 months in the platinum-resistant patients and 50% and 8.8 months in
      the platinum-sensitive patients. The main grade 3 to 4 hematological toxicity was
      neutropenia (56% of cases). After a median follow-up of 13.5 months, median
      progression-free survival was 5 months, and median overall survival was 23.5
      months. CONCLUSIONS: This E + G combination seems to be active and safe in
      platinum-resistant/refractory patients.

PMID- 20683402
TI  - Stage-specific embryonic antigen 4 expression in epithelial ovarian carcinoma.
AB  - INTRODUCTION: Stage-specific embryonic antigen 4 (SSEA-4) is a widely used marker
      to monitor the differentiation of pluripotent embryonic stem cells. Little is
      known about the expression pattern of SSEA-4 in solid tumors up to now. METHODS:
      In this study, we investigated the expression of SSEA-4 in 479 cases of various
      degrees of ovarian epithelial lesions by immunohistochemistry, consisting of 45
      normal ovarian epithelia, 110 benign serous ovarian cystadenomas, 68 borderline
      serous ovarian cystadenomas, 104 invasive serous ovarian carcinomas, 64 benign
      serous mucinous cystadenomas, 48 borderline mucinous ovarian cystadenomas, and 40
      invasive mucinous carcinomas. Moreover, the association between SSEA-4 expression
      and clinicopathological parameters was also evaluated. RESULTS: The expression of
      SSEA-4 was found to be increased from normal epithelium to benign cystadenoma and
      to borderline cystadenoma and adenocarcinoma in both serous and mucinous group.
      The loss or reduction of the expression of SSEA-4 was significantly correlated
      with more advanced tumor stage and poorer tumor cell differentiation.
      CONCLUSIONS: We therefore proposed that SSEA-4 may play a role during the
      oncogenesis of epithelial ovarian carcinoma and posses a tumor suppressor effect
      during malignancy promotion. It could be a potential therapy target in patients
      with epithelial ovarian carcinoma.

PMID- 20683403
TI  - Correlation between macroscopic and microscopic diseases on splenectomies
      performed in the surgical management of ovarian cancer.
AB  - BACKGROUND: Surgical management of primary or recurrent ovarian cancer with
      extensive upper abdominal disease may require splenectomy to achieve complete
      cytoreduction. The aims of this series were to correlate the macroscopic
      exploration with the microscopic analysis of the spleen and to evaluate the
      morbidity of patients submitted to this procedure for primary and recurrent
      disease. METHODS: Data concerning patients who underwent splenectomy at the time
      of management of the primary (initial group) or recurrent disease were reviewed.
      The characteristics and survival of patients were analyzed. The correlation
      between macroscopic suspected lesion and histological results and morbidity
      according to the Dindo classification was studied. RESULTS: From 1995 to 2008, 58
      patients (42 in the initial group and 16 in the recurrence group) underwent a
      splenectomy in our institution. Except for 3 cases requiring splenectomy for
      hemostatic reasons, the macroscopically suspected splenic lesion was confirmed by
      histology in 32 (80%) of 40 cases in the initial group and in 14 (93%) of 15
      cases in the recurrence group. Eighteen patients (26.5%) had a morbidity grade
      strictly superior to 2, and in all the factors we tested, only pelvic posterior
      exenteration was a risk factor for high morbidity (P = 0.02). CONCLUSIONS: When
      splenic lesions are macroscopically suspected during cytoreductive surgery for an
      ovarian cancer, most of the time the disease is confirmed by histology. When
      required to accomplish complete cytoreduction, splenectomy seemed to be
      justified.

PMID- 20683404
TI  - Ovarian cancer: the role of functional imaging as an end point in clinical
      trials.
AB  - The Gynaecological Cancer InterGroup conducts collaborative trials in gynecologic
      cancer and also aims to develop standards that can be used to strengthen all
      aspects of study methodology. There is an urgent need to develop more refined
      imaging end points that can be used as early treatment response biomarkers in
      ovarian cancer. Therefore, the Gynaecological Cancer InterGroup commissioned an
      expert position paper on the role of functional imaging as an end point in
      clinical trials in ovarian cancer. In this position paper, we state the
      limitation of current anatomical imaging methods used in clinical trials,
      highlight the potential of functional imaging, and provide key recommendations on
      the use of functional imaging as an end point in ovarian cancer clinical trials.

PMID- 20683405
TI  - Prognostic significance of supradiaphragmatic lymphadenopathy identified on
      preoperative computed tomography scan in patients undergoing primary
      cytoreduction for advanced epithelial ovarian cancer.
AB  - INTRODUCTION: It has been hypothesized that the supradiaphragmatic lymph nodes
      serve as the principal nodes for lymphatic drainage of the entire peritoneal
      cavity. The purpose of this study was to determine the prognostic significance of
      enlarged supradiaphragmatic nodes noted on preoperative computed tomographic (CT)
      scan in patients undergoing primary cytoreduction for advanced epithelial ovarian
      cancer (EOC). METHODS: We performed a retrospective chart review of all patients
      with stage III and IV EOC according to the International Federation of Gynecology
      and Obstetrics who had preoperative CT scans, including the supradiaphragmatic
      region, and had undergone primary cytoreductive surgery at our institution
      between January 1997 and June 2004. Scans were retrospectively reviewed by a
      radiologist. We defined supradiaphragmatic adenopathy as nodes measuring greater
      than 5 mm on the largest of 2 perpendicular measurements on the CT scan. The
      Fisher exact test was used to compare proportions. Kaplan-Meier curves and log
      rank tests were used for the survival analyses. RESULTS: A total of 212 evaluable
      patients were identified. All underwent attempted primary cytoreduction followed
      by systemic chemotherapy. None had any supradiaphragmatic nodes removed at
      primary cytoreduction. With a median follow-up time of 52 months, median overall
      survival for the entire cohort was 48 months. Of 212 patients, 92 (43%) had
      supradiaphragmatic adenopathy. Median survival was 50 months for patients without
      adenopathy and 45 months for patients with adenopathy (P = 0.09). Of the 212
      patients, 155 (73%) underwent optimal cytoreduction. In these patients, median
      survival was 55 months for the 91 without adenopathy and 50 months for the 64
      patients with supradiaphragmatic adenopathy (P = 0.09). CONCLUSIONS: We observed
      a trend toward worse survival in patients with enlarged supradiaphragmatic nodes.
      The prognostic impact of supradiaphragmatic adenopathy remains uncertain and
      deserves further study.

PMID- 20683406
TI  - Surveillance procedures for patients treated for endometrial cancer: a review of
      the literature.
AB  - OBJECTIVES: The aim of this review was to analyze the role of follow-up in
      patients treated for endometrial cancer and to provide some compelling issues
      that may contribute to improve daily practice while waiting for evidence-based
      guidelines. METHODS/MATERIALS: A literature search has been conducted in MEDLINE
      database using key words "endometrial neoplasms" and "follow up". RESULTS:
      Endometrial cancer represents the most common gynecologic malignancy after breast
      cancer. The overall recurrence rate is 13% and correlates with prognostic factors
      of the primary tumor. The anatomic sites of endometrial cancer relapse are mostly
      equivalently distributed between local (pelvic) and distant (abdominal and
      chest). Most endometrial cancer recurrences are symptomatic, even if vaginal
      vault relapses represent a particular setting of a more frequently asymptomatic
      disease. Most of endometrial cancer recurrences occur within 3 years since
      diagnosis of primary tumor. Long-term surveillance programs are mainly addressed
      to the early detection of recurrence, the rationale of follow-up being that an
      earlier diagnosis of relapse correlates with lower morbidity and mortality rates.
      Adjunctive objectives of routine follow-up are identification of treatment
      complications and detection of possible second tumors associated with endometrial
      cancer. CONCLUSIONS: No rationale (examination sensitivity/sensibility, cost
      effectiveness, or patient's survival benefit) is available today for any
      particular follow-up protocol; follow-up procedures should probably be tailored
      according to different prognostic factors; only physical examination, including
      pelvic-rectal examination, showed some utility in detecting recurrence. In this
      uncertain setting, follow-up interval should be defined with the consideration of
      the patient's will.

PMID- 20683407
TI  - The pattern of p14ARF expression in primary and metastatic human endometrial
      carcinomas: correlation with clinicopathological features and TP53 pathway
      alterations.
AB  - OBJECTIVES: Alterations of p53 pathway (p14(ARF)/MDM2/p53) play a crucial role in
      the development and progression of various human neoplasms, including endometrial
      carcinoma (EC). The aim of the current research was to examine the p14(ARF)
      expression pattern in primary ECs and corresponding metastatic lesions. MATERIALS
      AND METHODS: We studied 47 primary ECs and corresponding metastatic lesions
      applying immunohistochemistry and investigated the relationship between p14(ARF)
      overexpression and clinicopathological variables of carcinoma as well as TP53
      alterations. RESULTS: Protein expression was predominantly nuclear, present in 32
      (68%) of 47 primary cases and in 28 (60%) of 47 metastatic lesions. There were
      seven p14(ARF)-positive primary tumors showing negative reactivity in the
      metastatic lesions. On the other hand, 3 cases lacked protein immunoreactivity in
      the primary ECs but revealed weak nuclear staining in the corresponding
      metastases. A case of primary cervical adenocarcinoma metastasizing to the lymph
      nodes showed p14(ARF) expression both in the primary tumor and the corresponding
      metastases. A trend was found between the p14(ARF) expression in primary tumors
      and the presence of the neoplasms in the fallopian tube (P = 0.063), but none of
      the other clinicopathological variables of carcinoma was related to protein
      immunoreactivity in advanced-stage uterine neoplasms. The p14(ARF) expression in
      EC metastases was related to the presence of the primary tumor in the fallopian
      tube (P = 0.036). The p14(ARF) expression was not associated with unfavorable
      outcome both in the primary tumors (P = 0.302) and in the corresponding
      metastases (P = 0.217). There was also no relationship between the p14(ARF)
      expression pattern and TP53 pathway alterations. CONCLUSIONS: Altogether, the
      p14(ARF) protein is expressed in more than half of the primary ECs and metastatic
      lesions analyzed and is associated with the transtubal dissemination of the
      primary tumor. The pattern of the p14(ARF) expression is not associated with the
      alterations of other TP53 pathway members in advanced-stage human ECs.

PMID- 20683408
TI  - Long-term survival in patients with para-aortic lymph node metastasis with
      systematic retroperitoneal lymphadenectomy followed by adjuvant chemotherapy in
      endometrial carcinoma.
AB  - OBJECTIVE: The purposes of this study were to assess modified radical
      hysterectomy including systematic pelvic and para-aortic lymphadenectomy followed
      by adjuvant chemotherapy in patients with para-aortic lymph node (PAN) metastasis
      in endometrial carcinoma and to identify the multivariate independent prognostic
      factors for long-term survival during the past 10 years. METHODS: Between
      December 1987 and December 2002, we performed modified radical hysterectomy with
      bilateral salpingo-oophorectomy including systematic pelvic and para-aortic
      lymphadenectomy and peritoneal cytology in 284 endometrial carcinoma patients
      according to the classification of the International Federation of Gynecology and
      Obstetrics (stage IA, n = 66; stage IB, n = 96; stage IC, n = 33; stage IIA, n =
      5; stage IIB, n = 20; stage IIIA, n = 28; stage IIIC, n = 28; and stage IV, n =
      8) who gave informed consents at our institute. Patients with tumor confined to
      the uterus (stages IC and II) were treated by 3 courses of cyclophosphamide 750
      mg/m2, epirubicin 50 mg/m2, and cisplatin 75 mg/m2 regimen 3 to 4 weeks apart,
      and patients with extrauterine lesions involving adnexa and/or pelvic lymph node
      (PLN) were treated by 5 courses. In addition, 10 courses were given to patients
      with PAN metastasis. Patients with PLN metastasis received adjuvant chemotherapy,
      and adjuvant radiation was not part of our institutional protocol. For
      multivariate regression modeling with proportional hazards, the regression model
      of Cox was used. Survival curves were analyzed by the Kaplan-Meier method, and
      analysis of the differences was performed by the log-rank test. RESULTS: The
      overall incidence of retroperitoneal lymph node metastasis assessed by systematic
      pelvic and para-aortic lymphadenectomy was 12.0% (34/284) in stages I to IV
      endometrial carcinoma, and incidences of PLN and PAN metastases were 9.2%
      (26/284) and 7.4% (21/284), respectively. However, PAN metastasis rate is 50%
      (13/26) in patients with PLN metastasis. Univariate analysis of prognostic
      factors revealed that International Federation of Gynecology and Obstetrics
      clinical stage (P < 0.0001), histological finding (P = 0.0292), myometrial
      invasion (P < 0.0001), adnexal metastasis (P < 0.0001), lymphovascular space
      invasion (P < 0.0001), tumor diameter (P = 0.0108), peritoneal cytology (P =
      0.0001), and retroperitoneal lymph node metastasis (P < 0.0001) were
      significantly associated with 10-year overall survival. Survival was not
      associated with age (P = 0.1558) or cervical involvement (P = 0.1828). A
      multivariate analysis showed that adnexal metastasis (P = 0.0418) and
      lymphovascular space invasion (P = 0.0214) were significantly associated with 10
      year overall survival. The 5- and 10-year overall survival rates in patients with
      negative PAN were 96% and 93% versus 72% and 62% in patients with positive PAN (P
      = 0.006). CONCLUSIONS: It is suggested that surgery with systematic pelvic and
      para-aortic lymphadenectomy followed by adjuvant chemotherapy could improve long
      term survival in patients with PAN metastasis, although there are only 21
      patients with PAN metastasis.

PMID- 20683409
TI  - SNIPER: a novel assay for human papillomavirus testing among women in Guizhou,
      China.
AB  - OBJECTIVE: Clinically validate the SNIPER human papillomavirus (HPV) DNA assay
      for the detection of cervical intraepithelial neoplasia (CIN)2 or higher and CIN2
      or higher in a prospective cross-sectional screening study in Guizhou Province,
      China. METHODS: Between March and April, 2008, 1000 nonpregnant women aged 30 or
      older were recruited in Guizhou Province, China. Women positive by SNIPER or
      cytological examination were requested to return for follow-up. A biopsy of all
      colposcopically detected abnormalities was performed by quadrant. In normal
      quadrants, biopsies were obtained at the squamocolumnar junction (2-, 4-, 8-, and
      10-o'clock positions depending on the quadrant). Samples were placed in 2 mL of
      saline solution and maintained between 2 degrees C and 30 degrees C for up to 1
      week. One milliliter of this suspension was then prepared and tested. For
      polymerase chain reaction amplification, a pool of HPV primers was designed to
      amplify HPV DNA from 13 high-risk-HPV genotypes (types 16, 18, 31, 33, 35, 39,
      45, 51, 52, 56, 58, 59, and 68). Test characteristics were calculated according
      to standard definitions. RESULTS: One thousand women were screened; 175 tested
      HPV positive, 36 women tested negative but had positive Papanicolaou test
      results. All but 21 (90%) returned for follow-up. Median age and proportions
      having CIN2 or higher and CIN3 or higher differed by HPV status. Twenty-five
      women had CIN2 or higher and 16 had CIN3 or higher. The SNIPER assay was 93.3%
      and 94% sensitive and 86% and 85% specific for the detection of CIN2 or higher
      and CIN3 or higher, respectively. The positive predictive value was 17.4 % and
      9.9% for CIN2 or higher and CIN3 or higher, respectively. Negative predictive
      value approached 100% for CIN2 or higher and CIN3 or higher. CONCLUSION: The
      SNIPER assay is functionally competitive and in terms of cost holds an advantage
      over Hybrid Capture 2 in a Chinese healthcare market, and potentially others,
      around the world.

PMID- 20683410
TI  - Association between serum cytokine profiles and clearance or persistence of high
      risk human papillomavirus infection: a prospective study.
AB  - INTRODUCTION: The cytokines that may be associated with the clearance or
      persistence of high-risk human papillomavirus (HPV) infection in patients with
      mild dysplasia or less of the uterine cervix were determined. METHODS: A
      prospective study of 160 patients who harbored high-risk HPV with histologically
      confirmed mild dysplasia or less between January 2006 and August 2008 was
      performed. All patients were followed up at every 4 months during the first year.
      Human papillomavirus DNA tests by the Hybrid Capture 2 method (Digene,
      Gaithersburg, Md) were performed at every visit on all patients. Blood sampling
      was performed in all patients at their initial visit, and an enzyme-linked
      immunosorbent assay was used to measure the serum levels of interferon gamma,
      tumor necrosis factor alpha, and interleukins 6 and 10. RESULTS: Of the 160
      patients, 107 (66.9%) had clearance of HPV infection after 12 months of follow
      up. The median age of patients in the persistence group was significantly higher
      than that of patients in the clearance group (47 vs 38 years, respectively;
      range, 21-77 vs 21-71 years, respectively; P = 0.0009). In univariate analysis,
      the number of patients with serum negative for tumor necrosis factor alpha was
      significantly higher in the clearance group than the persistence group (P =
      0.0363). However, in multivariate logistic regression analysis, all 4 cytokines
      failed to show any significant association with the clearance or persistence of
      HPV infection. CONCLUSIONS: The baseline serum cytokine levels were not
      associated with the clearance or persistence of HPV infection. Systemic immunity
      may not influence the natural history of HPV infection.

PMID- 20683411
TI  - Prevalence and predictors of anxiety and depression among cervical cancer
      survivors in Korea.
AB  - PURPOSE: With increasing survival rates of women with cervical cancer, quality of
      life of the survivors becomes a more important issue. However, little is known
      about the mental health of cervical cancer survivors (CCSs). This study
      investigated the prevalence of anxiety and depression in CCSs compared with
      healthy controls and identified factors associated with multidimensional model
      including sociodemographic, clinical, functioning and well-being, and symptom
      variables. METHODS: The participants included 828 CCSs (mean time since
      treatment, 6.9 years) enrolled at 6 tertiary hospitals from 1983 to 2004 and 500
      control subjects selected randomly from a representative sample of Korean women.
      Subjects completed the following questionnaires: the Hospital Anxiety and
      Depression Scale, the European Organization for Research and Treatment of Cancer
      Quality of Life questionnaire-C30, its Cervical Cancer module, and the McGill
      Quality of Life Questionnaire. RESULTS: Hospital Anxiety and Depression Scale
      defined anxiety in CCSs did not differ from that in healthy controls (39.5% and
      32.2%, respectively; P = 0.218). Anxiety was significantly more prevalent in
      younger CCSs (< or = 50 years) than in controls (40% vs 26.4%, respectively; P <
      0.001). Hospital Anxiety and Depression Scale-defined depression was even lower
      in CCSs than in controls (34.6% vs 48.0%, respectively; P < 0.001). In
      multivariate analyses, the Hospital Anxiety and Depression Scale-defined anxiety
      and depression in CCSs were commonly associated with financial difficulty, poor
      body image, sexual inactivity, and low existential well-being. Low support and
      insomnia were uniquely related to anxiety, with older age and decrement role
      function uniquely related to depression. However, disease-related clinical
      factors were not related to either anxiety or depression. CONCLUSIONS: Cervical
      cancer survivors showed relatively good mental health compared with healthy
      controls; however, women who have low functioning and well-being could be at high
      risk of anxiety or depression or both.

PMID- 20683412
TI  - Shimodaira-Taniguchi conization method: its utility and reliability.
AB  - INTRODUCTION: Introduced in 1992, the Shimodaira-Taniguchi conization procedure
      addresses the disadvantages of the loop electrosurgical excision procedure by
      relying on a high frequency current of 150 W and a triangular probe with a 0.25
      mm linear excision electrode to extract a single informative specimen. We
      conducted a retrospective study to evaluate Shimodaira-Taniguchi conization as a
      conservative therapy for cervical intraepithelial neoplasia (CIN) and
      microinvasive cancer of the cervix. METHODS: Subjects were 455 patients who
      underwent Shimodaira-Taniguchi conization for CIN, carcinoma in situ,
      adenocarcinoma in situ, or stage IA microinvasive cervical carcinoma at our
      hospital from January 2005 to December 2008. Patient follow-up ranged from 13 to
      60 months. Clinical data were obtained and evaluated. RESULTS: Mean operation
      time was 11 minutes, and average blood loss was 9.9 mL. Margins were positive in
      178 (39.1%) cases. Postsurgical complications occurred in 61 patients, with
      secondary hemorrhage occurring in 46 patients. None required transfusion. None
      were lost to follow-up, and there was no disease-related death. Disease recurred
      in 6 (1.3%) patients: 4 with a positive excision margin and 2 with a negative
      margin. Cervical stenosis occurred in 15 (3.3%) patients, 3 of whom suffered
      cervical obstruction, including 1 with dysmenorrhea who underwent hysterectomy.
      In most cases (n = 357, 78%), a single adequate specimen was extracted.
      CONCLUSIONS: As a conservative treatment for CIN and microinvasive cervical
      cancer, Shimodaira-Taniguchi conization is useful. It is easy, provides adequate
      histologic specimens (often singular), and results in few postoperative
      complications.

PMID- 20683413
TI  - Abdominal scar recurrences of cervical cancer: incidence and characteristics: a
      case-control study.
AB  - BACKGROUND: Tumor recurrence in the surgical scar after radical hysterectomy for
      cervical cancer has been reported, but the incidence is unknown. Facts about
      patient and tumor characteristics and follow-up are lacking. The objective of
      this study was to analyze the incidence and characteristics of cervical cancer
      scar recurrences. METHODS: All patients who were surgically treated for cervical
      cancer in our center between 1984 and 2007 were reviewed for scar recurrences.
      For each case, 5 random controls were selected. Clinical characteristics were
      compared between the cases and controls. RESULTS: Eleven (1.3%) of 842 patients
      developed a scar recurrence. Mean time between surgery and scar recurrence was 16
      months (range, 2-45 months). For 8 patients (73%), the scar recurrence was the
      first disease recurrence. Five patients (45%) died, and 2 (18%) were lost to
      follow-up. Mean time between scar recurrence and death was 9 months. Ninety-one
      percent of the cases had recurrent disease besides the scar recurrence during
      follow-up. The case group had a higher percentage of advanced FIGO (International
      Federation of Gynecology and Obstetrics) stage and postoperatively found
      involvement of parametria or resection margins and tumor diameter greater than 4
      cm, whereas lymph nodes were more often involved in the control group.
      CONCLUSIONS: The incidence of scar recurrences after primary surgery for cervical
      cancer was 1.3%. Time to development was variable, and prognosis was poor.
      Besides higher FIGO stage and concurrent unfavorable pathological
      characteristics, we found no outstanding characteristics of patients with scar
      recurrence. Scar recurrences go hand in hand with recurrent disease at other
      locations and seem a manifestation of tumors with extensive metastatic potential.

PMID- 20683414
TI  - Value of PET-CT in avoiding multimodality therapy in operable cervical cancer.
AB  - BACKGROUND: Posttreatment morbidity of multimodality therapy is substantially
      higher than either radical surgery or chemoradiation alone. Preoperative
      prediction of positive nodes limits optimal selection of the primary treatment
      modality. Computed tomography (CT) and magnetic resonance imaging have been tried
      for nodal assessment with modest results. Positron emission tomography (PET)
      combined with CT seems to be promising in this regard. This clinicopathologic
      study assesses the value of PET-CT in predicting nodal metastasis and avoiding
      multimodality therapy. MATERIALS AND METHODS: Eighty patients with clinically
      operable cervical cancer underwent PET-CT during the preoperative evaluation
      followed by radical hysterectomy. Adjuvant chemoradiation was administered when
      indicated by histopathologic findings. The histopathologic finding of the pelvic
      nodes was correlated with the PET-CT findings for nodal metastasis. The chi2 test
      was used as the test of significance in the statistical analysis. OBSERVATIONS:
      Of 62 patients found PET-CT negative for nodal disease, 52 were true negative,
      whereas 10 were false negative on histopathologic examination. On the other hand,
      14 of 18 patients found PET-CT positive for nodal disease were true positives.
      Specificity, sensitivity, positive predictive value, and negative predictive
      value of PET-CT in nodal assessment were found to be 92.8, 58.33, 77.7, and 83.8,
      respectively. Twenty-four patients (30%) with pelvic nodes positive for disease
      on histopathologic examination were administered adjuvant chemoradiation. Had we
      operated only on those patients who were PET-CT negative for nodal disease, 10 of
      62 patients would have required adjuvant chemoradiation for positive nodes.
      Eighteen patients found PET-CT positive for nodal disease would be treated with
      primary chemoradiation. Inclusion of PET-CT in the decision-making process for
      primary surgery versus primary chemoradiation would allow 87.5% patients to
      receive a single modality of treatment (65%, only surgery; 22.5%, only
      chemoradiation) and the proportion of patients requiring multimodality treatment
      would reduce significantly from 30% to 12.5% (P < 0.01). CONCLUSION: Positron
      emission tomography combined with CT in the evaluation of operable cervical
      cancer can help in the optimal selection of patients for surgery such that
      multimodality treatment with its attendant increase in morbidity is avoided.

PMID- 20683415
TI  - Region-wise distribution of high-risk human papillomavirus types in squamous cell
      carcinomas of the cervix in India.
AB  - HYPOTHESIS: Assessment of the prevalence and type distribution of human
      papillomavirus (HPV) in squamous cell carcinomas (SCC) of the cervix across India
      was undertaken to estimate the impact of available prophylactic HPV-L1 vaccines
      in the country and to find out additional types that might be needed to be
      incorporated in second-generation vaccines. METHODS: High-risk (HR) HPVs were
      genotyped from 667 histopathologically confirmed cases of SCC from 6 different
      centers representing 4 regions across India: Advanced Centre for Treatment,
      Research and Education in Cancer, Mumbai; All India Institute of Medical
      Sciences, New Delhi; Cancer Foundation of India, Kolkata; Christian Medical
      College, Vellore; Kidwai Memorial Institute of Oncology, Bangalore; and Regional
      Cancer Center, Thiruvananthapuram. Human papillomaviruses in tumor biopsies were
      analyzed by Xcytonscreen HPV based on PGMY09/11 multiplex polymerase chain
      reaction and reverse dot blot assay. RESULTS: Overall viral prevalence across
      India was not different; 92.1% of 667 cases harbored HPV; 8% were negative.
      Infection with single HR type was seen in 86.8%: predominant types being HPV-16
      followed by HPV-18, -45, -73, -31, -56, -52, -58, -59, -33, -68, -51, -35, -26,
      and -39. Human papillomavirus types 16/18-positive fraction formed 79.6%; other
      types comprised 12.4%. CONCLUSIONS: Prophylactic HPV-16/18-L1 vaccines would
      provide greater than 75% protection against SCC in India. Ranking and frequencies
      of non-16/18 types were different from earlier reports. Hence, considering the
      possibility of promotion of persistence of nonvaccine types in the vaccinees due
      to original antigenic sin and the lack of organized screening programs in India,
      a broad-based vaccine approach would be appropriate.

PMID- 20683416
TI  - The inflammation-based Glasgow Prognostic Score predicts survival in patients
      with cervical cancer.
AB  - OBJECTIVES: The Glasgow Prognostic Score (GPS) is known to reflect the degree of
      tumor-associated cachexia and inflammation and is associated with survival in
      various malignancies. We investigated the value of the GPS in patients with
      cervical cancer. METHODS: We included 244 consecutive patients with cervical
      cancer in our study. The pretherapeutic GPS was calculated as follows: patients
      with elevated C-reactive protein serum levels (>10 mg/L) and hypoalbuminemia (<35
      g/L) were allocated a score of 2, and patients with 1 or no abnormal value were
      allocated a score of 1 or 0, respectively. The association between GPS and
      survival was evaluated by univariate log-rank tests and multivariate Cox
      regression models. The GPS was correlated with clinicopathologic parameters as
      shown by performing chi2 tests. RESULTS: In univariate analyses, GPS (P < 0.001,
      P < 0.001), International Federation of Gynecology and Obstetrics (FIGO) stage (P
      < 0.001, P < 0.001), and lymph node involvement (P < 0.001, P < 0.001), but not
      patients' age (P = 0.2, P = 0.07), histological grade (P = 0.08, P = 0.1), and
      histological type (P = 0.8, P = 0.9), were associated with disease-free and
      overall survival, respectively. In a multivariate analysis GPS (P = 0.03, P =
      0.04), FIGO stage (P = 0.006, P = 0.006), and lymph node involvement (P = 0.003,
      P = 0.002), but not patients' age (P = 0.5, P = 0.5), histological grade (P =
      0.7, P = 0.6), and histological type (P = 0.4, P = 0.6) were associated with
      disease-free and overall survival, respectively. The GPS was associated with FIGO
      stage (P < 0.001) and histological grade (P = 0.02). CONCLUSIONS: The GPS can be
      used as an inflammation-based predictor for survival in patients with cervical
      cancer.

PMID- 20683417
TI  - Women's knowledge of Pap smear test and human papillomavirus: acceptance of HPV
      vaccination to themselves and their daughters in an Islamic society.
AB  - OBJECTIVE: Cancer of cervix uteri is the second most common cancer among women,
      and it has been shown to be caused by human papillomavirus (HPV) infection in
      more than 99% of cases. We surveyed Muslim Turkish women, who mostly accept
      talking about sex as a taboo, to examine their knowledge about Papanicolaou (Pap)
      smear test, HPV, HPV vaccine, and their attitude toward vaccination to themselves
      and their daughters. METHODS: We surveyed 525 women aged between 19 and 53 years
      to examine their knowledge about cervical cancer screening Pap smear test, HPV,
      HPV vaccine, and their attitude toward vaccination to themselves and their
      daughters with a questionnaire that is consisted of 5 parts with a total of 31
      items. RESULTS: The knowledge of cervical screening was high (70%), and 51% of
      the subjects were at least once had a Pap smear test, but most respondents (56%)
      had never heard of HPV. For most women, recommendations from health workers (67%)
      were the major influences in deciding to get vaccinated. CONCLUSIONS: The
      importance of successful introduction on the vaccine by the drug providers and
      health care professionals in Turkey was shown in this present study with a high
      rate of awareness of cervical cancer vaccine. "Early-age vaccination knowledge"
      before any sexual contact is probably due to the correct education of mothers by
      health care professionals. The professionals should be educated and trained about
      HPV, vaccination, and its relation with cervical cancer to increase the knowledge
      about it.

PMID- 20683418
TI  - Conservative treatment of stage IA1 adenocarcinoma of the uterine cervix with a
      long-term follow-up.
AB  - OBJECTIVES: The adenocarcinoma of the uterine cervix tends to arise in women of
      childbearing age. Conservative treatment by conization is an alternative to a
      hysterectomy that allows future pregnancy; however, much less is known about the
      management of adenocarcinoma because of its rarity and relatively short time
      frame of follow-up. The purpose of this study was to determine the long-term
      outcome of patients treated by conization alone. METHODS: All patients diagnosed
      to have FIGO (International Federation of Gynecology and Obstetrics) stage IA1
      cervical adenocarcinoma between 1990 and 2004 with more than 5 years' follow-up
      at 2 institutions were reviewed. Information was abstracted on clinical data
      including margin status of conization and recurrence. RESULTS: Twenty-seven
      patients were identified, and 10 patients who expressed a strong desire to
      preserve fertility were offered a conization and careful surveillance without
      hysterectomy. The median age was 35 years, and 40% were nulliparous. All tumors
      were endocervical-type adenocarcinoma, and all tumors were grade 1. None had
      lymphovascular space invasion. Two patients had a repeated conization because of
      a positive margin. No recurrence was observed during an average follow-up of 75
      months. CONCLUSIONS: Although further studies on the management of microinvasive
      cervical adenocarcinoma are desirable, conization seems to be acceptable
      treatment modality for patients with stage IA1 cervical adenocarcinoma who desire
      to preserve their fertility. A careful and long-term follow-up is needed because
      of lack of sufficient evidence for the safety of this treatment.

PMID- 20683419
TI  - Specific human papillomavirus types and other factors on the risk of cervical
      intraepithelial neoplasia: a case-control study in Korea.
AB  - OBJECTIVE: Cervical neoplasia is attributed to a persistent human papillomavirus
      (HPV) infection. We performed a hospital-based, case-control study to evaluate
      the associations of HPV genotypes and other cofactors with cervical
      intraepithelial neoplasia (CIN). METHODS: A total of 158 women were enrolled
      after we received their informed consent, and the control group (the non-CIN
      group; n = 80) was selected from women at St Paul's Health Promotion Center. The
      CIN group (n = 78) was enrolled from the outpatient clinics at Kangnam St Mary's
      Hospital. Cervical intraepithelial neoplasia was confirmed with colposcopic
      guided biopsy or loop electrosurgical excision procedure-conization. A structured
      questionnaire, Papanicolaou test, and HPV testing were completed. We compared
      each risk factor using chi2 tests and simple logistic regression analysis between
      the CIN and non-CIN groups. Finally, odds ratios (ORs) were calculated again by
      multiple logistic regression analysis. RESULTS: The most frequent HPV types in
      CIN were HPV-16, HPV-58, HPV-31/-33, and HPV-35/-56. The OR of the A9 group (HPV
      16, HPV-31, HPV-33, HPV-35, HPV-52, HPV-58) was 22.7 (95% confidence interval
      [CI], 8.3-62.5), that of the A6 group (HPV-53, HPV-56, HPV-66) was 2.9 (95% CI,
      1.1-7.5), and that of the A7 group (HPV-18, HPV-39, HPV-45, HPV-59, HPV-68) was
      1.5. Sexual debut before 20 years old had significantly higher OR than did a
      sexual debut after 30 years (OR, 32.9; 95% CI, 2.8-364.7). The OR for CIN in
      single women versus married women was 6.2 (95% CI, 2.5-15.2). Compared with
      parous women (parity >3), nonparous women had a higher OR (95% CI, 1.4-16.7). On
      the multiple logistic regression analysis including the sexual debut age, the
      marital status, parity, cytology, and the HPV groups, the A9 group had a
      significant OR for CIN (6.1; 95% CI, 1.6-23.6). CONCLUSIONS: The risk of CIN was
      higher for women infected with the HPV-A9 group after multiple logistic
      regression analysis. The other clinical risk factors were not significant factors
      of CIN.

PMID- 20683420
TI  - Patient outcome study of concurrent chemoradiation, external beam radiotherapy,
      and high-dose rate brachytherapy in locally advanced carcinoma of the cervix.
AB  - INTRODUCTION: A regimen of concurrent chemoradiation for definitive treatment of
      cervical cancer is widely used. This retrospective review has been conducted to
      determine the outcomes and late toxic effect associated with the specific regimen
      of whole-pelvic external beam radiotherapy of 45 Gy in 25 fractions with
      parametrial boosts of 5.4 or 9 Gy and HDR brachytherapy (BT) of 30 Gy in 5
      fractions to point A delivered by tandem and ring. This protocol is accepted by
      the Gynecological Oncology Group and endorsed by the American Brachytherapy
      Society, but no late toxic effect data have been reported. MATERIALS AND METHODS:
      The electronic records of sequential patients treated definitively at the
      Sunnybrook Odette Cancer Centre between January 2006 and December 2008 were
      reviewed. Patient-, tumor-, and treatment-related details (including external
      beam radiotherapy, BT, and chemotherapy) were obtained. Outcome measures included
      disease-free status, dates and sites of first recurrence, survival, and grade 3/4
      late toxic effect results (Common Terminology Criteria Adverse Events 3.0
      criteria). Exclusion criteria were no follow-up or a planned alternative regimen.
      RESULTS: One hundred twenty-two patients (+11 excluded) were treated with a
      median follow-up of 18 months from diagnosis. The actuarial 2-year disease-free
      survival rate was 70%. The median time to recurrence was 8 months (range, 2-22
      months). The median time to toxic effect was 10 months (range 4-27 months). Grade
      3/4 toxic effect was observed in 13 patients (11%). The actuarial grade 3/4 toxic
      effect rate at 2 years was 14%. CONCLUSIONS: Despite a relatively short follow
      up, the toxicity of this regimen seems high compared with other retrospective
      series, although pelvic control is good. Consideration should be given to a
      reduction in BT dose alternatively when feasible image-guided BT may allow
      maintenance of tumor dose with reduced dose to organs at risk.

PMID- 20683421
TI  - The use of acellular dermal allograft for vulvovaginal reconstruction.
AB  - BACKGROUND: Many different techniques that require the surgeon to harvest
      autologous tissue to create a neovagina have been described in the literature.
      TECHNIQUE: We describe a technique for creating a neovagina with the use of an
      acellular dermal allograft as a replacement for split-thickness skin graft. Three
      patients are presented who had a successful creation of a neovagina with this
      technique. The indications for vaginoplasty include vaginal agglutination from
      lichen planus, squamous cell carcinoma of the vagina, and vaginal agenesis.
      CONCLUSION: The creation of a neovagina using an acellular dermal allograft can
      be successfully accomplished in patients undergoing constructive and exenterative
      procedures. The use of an acellular dermal allograft decreases operative time and
      decreases the incidence of postoperative morbidity because harvesting autologous
      tissue for the neovagina is not required.

PMID- 20683422
TI  - Laparoscopic ovarian transposition before pelvic irradiation: a Saudi tertiary
      center experience.
AB  - OBJECTIVE: To report the authors' experience with laparoscopic ovarian
      transposition and ovarian function preservation in women who require pelvic
      irradiation as part of their cancer therapy. DESIGN: Cohort study. SETTING: The
      gynecologic oncology service in a referral tertiary/quaternary medical center in
      Saudi Arabia. PATIENTS: Twenty-three premenopausal patients treated with
      radiotherapy for a pelvic malignancy. INTERVENTIONS: Laparoscopic ovarian
      transposition to paracolic gutters with uterine conservation. MAIN OUTCOME
      MEASURES: Preservation of ovarian function assessed by patients' symptoms and
      serum follicle-stimulating hormone level. RESULTS: Bilateral laparoscopic ovarian
      transposition was performed in 23 patients: 15 with cervical cancer, 4 with
      rectal cancer, 3 with Ewing sarcoma, and 1 with Hodgkin lymphoma. No immediate
      intraoperative or postoperative complications were observed. Three patients were
      lost to follow-up. Ovarian preservation was achieved in 13 (65%) of 20 patients.
      Seven patients with low follicle-stimulating hormone levels had regular uterine
      bleeding at follow-up. CONCLUSIONS: Laparoscopic ovarian transposition is a safe
      and effective procedure for preserving ovarian function. This procedure should be
      considered in all premenopausal women who need to undergo pelvic irradiation as
      part of their cancer treatment.

PMID- 20683423
TI  - Evaluating contemporary radiotherapy approaches in the primary treatment of
      cervical cancer.
AB  - PURPOSE: Radiotherapy with concurrent cisplatinum-based chemotherapy became a
      standard recommendation for the management of advanced cervical cancer in 1999.
      We reviewed our experience with this approach to determine the impact on patient
      outcomes. METHODS: A retrospective review of all cervical cancer patients treated
      with curative intent using radical radiotherapy +/- chemotherapy from 1992 to
      2005 was performed. Survival and relapse rates were analyzed using the Kaplan
      Meier method and were compared using the log-rank test. RESULTS: During this
      period, 224 treated patients were identified: 153 (68%) were treated between 1992
      and 1999 (group 1) and 71 (32%) were treated after 1999 (group 2). The median age
      was 53 and 55 years with a median follow-up of 49 and 34 months for groups 1 and
      2, respectively. Stage classification and histological diagnosis were similar for
      both groups. Treatment usually consisted of external beam pelvic radiotherapy (40
      45 Gy in 20-25 fractions) followed by low-dose rate brachytherapy (35-40 Gy to
      point A). Chemotherapy consisted of weekly intravenous cisplatinum (40 mg/m2)
      given concurrently with pelvic radiation. The proportion of patients receiving
      chemotherapy increased significantly after 1999, 12% in group 1 compared with 79%
      in group 2 (P < 0.01). The 5-year overall survival (OS) and progression-free
      survival (PFS) rates were 53% and 54% for group 1 and 64% and 67% for group 2.
      The improvement in PFS for group 2 approached statistical significance (P =
      0.06), but the difference in OS did not. CONCLUSIONS: There has been a
      significant increase in the use of concurrent chemoradiation for cervical cancer
      treatment after 1999, and this seems to have led to higher rates of PFS and OS,
      although these have yet to achieve statistical significance.

PMID- 20683424
TI  - The development of priority cervical cancer trials: a Gynecologic Cancer
      InterGroup report.
AB  - Since the late 1990s, when a spate of US studies reported the benefit of
      chemoradiation for cervical cancer, there has been a dearth of clinical trials in
      cervical cancer. This requires to be addressed with urgency because this disease
      is responsible for a quarter of a million deaths globally each year, mostly in
      developing countries, but therapeutic advances are required in all health care
      settings. The Gynecologic Cancer InterGroup (GCIG) is a worldwide collaborative
      of leading national groups that develops and promotes multinational trials in
      gynecologic cancer. In recognition of the pressing need for action, the GCIG
      convened an international meeting with expert representations from most of the
      GCIG groups and selected large centers in low- and middle-income countries. The
      focus was to identify consensus on several concepts for clinical trials, which
      would be developed and promoted by the GCIG and launched with major international
      participation. The first half of the meeting was devoted to a resume of the
      current state of the knowledge and identifying the gaps most needing new
      evidence. The second half of the meeting was concerned with achieving consensus
      on the way forward. There were 2 principal outcomes. The first was a proposal to
      establish, under the umbrella of GCIG, a cervical cancer trials network of
      centers from countries currently outside GCIG (Eastern Europe, India, Thailand,
      Southern Africa, and South and Central America), which could increase
      international participation in trials, conducted within the principles of good
      clinical practice. The second was to identify the priorities for clinical trials.
      These included additional systemic therapy before or after chemoradiation; less
      radical surgery for small, early-stage tumors; the use of fewer fractions to
      improve cost-effectiveness of treatment in centers with limited resources; and
      chemotherapy to improve resectability of bulky tumors.

PMID- 20683425
TI  - Immature teratoma of ovary composed largely of choroid plexus.

PMID- 20683426
TI  - Influence of Dynesys system screw profile on adjacent segment and screw.
AB  - STUDY DESIGN: Displacement-controlled finite element analysis was used to
      evaluate the mechanical behavior of the lumbar spine after insertion of the
      Dynesys dynamic stabilization system. OBJECTIVE: This study aimed to investigate
      whether different depths of screw placement of Dynesys would affect load sharing
      of screw, range of motion (ROM), annulus stress, and facet contact force. SUMMARY
      OF BACKGROUND DATA: In clinical follow-up, a high rate of screw complications and
      adjacent segment disease were found after using Dynesys. The pedicle screw in the
      Dynesys system is not so easy to implant into the standard position and causes
      the screw to protrude more prominently from the pedicle. Little is known about
      how the biomechanical effects are influenced by the Dynesys screw profile.
      METHODS: The Dynesys was implanted in a 3-dimensional, nonlinear, finite element
      model of the L1 to L5 lumbar spine. Different depths of screw position were
      modified in this model by 5 and 10 mm out of the pedicle. The model was loaded to
      150 N preload and controlled the same ROMs by 20, 15, 8, and 20 degrees in
      flexion, extension, torsion, and lateral bending, respectively. Resultant ROM,
      annulus stress, and facet contact force were analyzed at the surgical and
      adjacent level. RESULTS: Under flexion, extension, and lateral bending, the
      Dynesys provided sufficient stability at the surgical level, but increased the
      ROM at the adjacent level. Under flexion and lateral bending, the Dynesys
      alleviated annulus stress at the surgical level, but increased annulus stress at
      the adjacent level. Under extension, the Dynesys decreased facet loading at the
      surgical level but increased facet loading at the adjacent level. CONCLUSIONS:
      This study found that the Dynesys system was able to restore spinal stability and
      alleviate loading on disc and facet at the surgical level, but greater ROM,
      annulus stress, and facet loading were found at the adjacent level. In addition,
      profile of the screw placement caused only a minor influence on the ROM, annulus
      stress, and facet loading, but the screw stress was noticeably increased.

PMID- 20683427
TI  - Preemptive retransplant for BK virus nephropathy without concurrent transplant
      nephrectomy.

PMID- 20683428
TI  - Mammalian tissue-free liberase: a new GMP-graded enzyme blend for human islet
      isolation.

PMID- 20683429
TI  - The effect of truncated collagenase class I isomers on human islet isolation
      outcome.

PMID- 20683430
TI  - Effects of neutrophil elastase inhibitor on progression of acute lung injury
      after liver transplantation.

PMID- 20683431
TI  - Common vascular endothelial growth factor variants and risk for posttransplant
      Kaposi sarcoma.

PMID- 20683433
TI  - Troponin I and cardiovascular events in transplant patients.

PMID- 20683434
TI  - Clara cell secretory protein and surfactant protein-D do not predict
      bronchiolitis obliterans syndrome after lung transplantation.

PMID- 20683435
TI  - Mixed intoxication with Aconitum nappellans (monkshood) and Digitalis grandiflora
      (large yellow foxglove).
AB  - BACKGROUND: Intoxications are frequent and relevant medical problems in emergency
      units. CASE REPORT: We report of a mixed intoxication with monkshood and large
      yellow foxglove. A 39-year-old mentally ill drug addict, intent on committing
      suicide, swallowed an undefined amount of chaffed monkshood and large yellow
      foxglove. The typical symptoms of an intoxication occurred, including high-grade
      ventricular and supraventricular tachyarrhythmias, colic abdominal pain, and
      peripheral paralysis. After activated charcoal was repeatedly administered as
      well as FAB digitalis-antibodies, a lasting normalisation of the heart rhythm set
      in and a release of the clinical symptoms could be observed. CONCLUSIONS: FAB
      antibodies are a safe antidote for herbal digitalis intoxication. Therapy of
      choice for an aconitum poisoning is activated charcoal and intensive monitoring.

PMID- 20683436
TI  - Off-tumor target--beneficial site for antiangiogenic cancer therapy?
AB  - Antiangiogenic cancer therapy is based on agents that target blood vessels of the
      tumor to inhibit its growth. However, experience from the clinic demonstrates
      that survival benefits following antiangiogenic therapy do not always correlate
      with tumor size and growth inhibition. Emerging evidence shows that delivery of
      antiangiogenic drugs might induce systemic alterations of the vasculature that
      modulate the function of various tissues and organs. Normalization of tissues and
      organs by antiangiogenic therapy may be an important mechanism underlying the
      survival benefits seen in patients with cancer who suffer cancer-associated
      systemic syndromes. This new concept has been validated in preclinical tumor
      models, and responses in patients have positively correlated with clinical
      benefits.

PMID- 20683437
TI  - Weekly paclitaxel in the treatment of recurrent ovarian cancer.
AB  - Weekly paclitaxel is a highly active and well tolerated regimen that is
      increasingly being adopted for the treatment of relapsed ovarian cancer. This
      regimen is usually administered at 80-90 mg/m(2)/week, and the use of a 1 h
      infusion helps minimize myelosuppression. When compared with the 3-weekly
      schedule, weekly paclitaxel is better tolerated, with a reduced frequency of
      grade 3-4 toxic effects. Single-agent weekly paclitaxel for relapsed ovarian
      cancer yields response rates in the range of 20-62%; however, response duration
      can be short. Responses to weekly paclitaxel have been observed in patients whose
      tumors are resistant to 3-weekly paclitaxel. The level of activity of weekly
      paclitaxel for relapsed disease has led to its detailed evaluation in the first
      line setting, and interest has been enhanced by the results of a Japanese
      Gynecological Oncology Group study that demonstrated a survival advantage for
      weekly paclitaxel compared with 3-weekly paclitaxel in combination with
      carboplatin as initial treatment. The enhanced efficacy of weekly paclitaxel may
      be due to greater drug exposure, a direct antiangiogenic effect, or both. Current
      research topics include the combination of weekly paclitaxel with molecular
      targeted agents and the use of molecular profiling to better select patients for
      treatment.

PMID- 20683438
TI  - Prevalence and burden of pediatric-onset systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a chronic, multisystem autoimmune disease
      with a highly variable clinical course. Pediatric-onset SLE (pSLE) represents 10
      20% of all SLE cases, and is associated with higher disease severity, including
      more-rapid damage accrual, than adult-onset SLE. As in adults, pSLE disease
      expression varies according to ethnicity, with a milder disease course in white
      patients. The majority of pSLE patients will have developed damage within 5-10
      years of disease onset, most frequently involving the musculoskeletal, ocular,
      renal and neuropsychiatric systems. Owing to improvements in disease management
      and recognition over the past 20-30 years, patients now live longer, but as a
      result have increased disease damage. Premature atherosclerosis and osteoporosis
      have become increasingly prevalent morbidities in pSLE patients. Early
      atherosclerosis leads to a considerable rise in cardiovascular and
      cerebrovascular events, and failure to develop adequate peak bone mass during
      adolescence-a crucial period of bone accrual-is likely to lead to early
      osteoporosis and fractures. Patients with pSLE have an incurable, potentially
      devastating disease that occurs during a vulnerable period of psychosocial
      development, leading to specific and unique psychosocial stressors. Additional
      large, long-term follow-up studies in pSLE are needed to better understand the
      disease prognosis and to facilitate development of tailored treatments.

PMID- 20683439
TI  - Pathogenetic mechanisms in the initiation and perpetuation of Sjogren's syndrome.
AB  - Sjogren's syndrome (SS), a chronic autoimmune disorder, particularly compromises
      the function of exocrine glands. The involvement of these glands is characterized
      by focal, mononuclear cell infiltrates that surround the ducts and replace the
      secretory units. The pathogenetic mechanisms of this autoimmune exocrinopathy
      have not been fully elucidated. Immunologically-activated or apoptotic glandular
      epithelial cells that expose autoantigens in genetically predisposed individuals
      might drive autoimmune-mediated tissue injury. Alterations in several immune
      mediators, such as upregulation of type I interferon-regulated genes, abnormal
      expression of B-cell-activating factor and activation of the interleukin-23-type
      17 T-helper cell pathway, have been reported. Extension of the pathological
      process that affects the exocrine glands into periepithelial and extraepithelial
      tissue can cause a considerable percentage of patients to exhibit systemic
      findings that involve the lungs, liver or kidneys. These manifestations develop
      as a result of lymphocytic invasion or an immune-complex-mediated process, or
      both, and present as skin vasculitis coupled with peripheral neuropathy or
      glomerulonephritis (or both). Patients with systemic extraepithelial
      manifestations display low serum levels of the complement component C4 and mixed
      type II cryoglobulins, and show an increased risk of developing non-Hodgkin
      lymphoma, thereby reflecting an overall worse prognosis with higher mortality
      rates than those without extraepithelial manifestations.

PMID- 20683440
TI  - Genetic epidemiology of age-related osteoporosis and its clinical applications.
AB  - Osteoporosis is an important and complex disorder that is highly prevalent
      worldwide. This disease poses a major challenge to modern medicine and its
      treatment is associated with high costs. Numerous studies have endeavored to
      decipher the pathogenesis of this disease. The clinical assessment of patients
      often incorporates information about a family history of osteoporotic fractures.
      Indeed, the observation of an increased risk of fracture in an individual with a
      positive parental history of hip fracture provides strong evidence for the
      heritability of osteoporosis. The onset and progression of osteoporosis are
      generally controlled by multiple genetic and environmental factors, as well as
      interactions between them, with rare cases determined by a single gene. In an
      attempt to identify the genetic markers of complex diseases such as osteoporosis,
      there has been a move away from traditional linkage mapping studies and candidate
      gene association studies to higher-density genome-wide association studies. The
      advent of high-throughput technology enables genotyping of millions of DNA
      markers in the human genome, and consequently the identification and
      characterization of causal variants and loci that underlie osteoporosis. This
      Review presents an overview of the major findings since 2007 and clinical
      applications of these genome-wide linkage and association studies.

PMID- 20683441
TI  - Integrating anaerobic/aerobic sensing and the general stress response through the
      ArcZ small RNA.
AB  - The alternative sigma factor RpoS responds to multiple stresses and activates a
      large number of genes that allow bacteria to adapt to changing environments. The
      accumulation of RpoS is regulated at multiple levels, including the regulation of
      its translation by small regulatory RNAs (sRNAs). A library of plasmids
      expressing each of 26 Escherichia coli sRNAs that bind Hfq was created to
      globally and rapidly analyse regulation of an rpoS-lacZ translational fusion. The
      approach can be easily applied to any gene of interest. When overexpressed, four
      sRNAs, including OxyS, previously shown to repress rpoS, were observed to repress
      the expression of the rpoS-lacZ fusion. Along with DsrA and RprA, two previously
      defined activators of rpoS translation, a third new sRNA activator, ArcZ, was
      identified. The expression of arcZ is repressed by the aerobic/anaerobic-sensing
      ArcA-ArcB two-component system under anaerobic conditions and adds translational
      regulation to the ArcA-ArcB regulon. ArcZ directly represses, and is repressed
      by, arcB transcription, providing a negative feedback loop that may affect
      functioning of the ArcA-ArcB regulon.

PMID- 20683442
TI  - Arabidopsis S6 kinase mutants display chromosome instability and altered RBR1-E2F
      pathway activity.
AB  - The 40S ribosomal protein S6 kinase (S6K) is a conserved component of signalling
      pathways controlling growth in eukaryotes. To study S6K function in plants, we
      isolated single- and double-knockout mutations and RNA-interference (RNAi)
      silencing lines in the linked Arabidopsis S6K1 and S6K2 genes. Hemizygous
      s6k1s6k2/++ mutant and S6K1 RNAi lines show high phenotypic instability with
      variation in size, increased trichome branching, produce non-viable pollen and
      high levels of aborted seeds. Analysis of their DNA content by flow cytometry, as
      well as chromosome counting using DAPI staining and fluorescence in situ
      hybridization, revealed an increase in ploidy and aneuploidy. In agreement with
      this data, we found that S6K1 associates with the Retinoblastoma-related 1 (RBR1)
      E2FB complex and this is partly mediated by its N-terminal LVxCxE motif.
      Moreover, the S6K1-RBR1 association regulates RBR1 nuclear localization, as well
      as E2F-dependent expression of cell cycle genes. Arabidopsis cells grown under
      nutrient-limiting conditions require S6K for repression of cell proliferation.
      The data suggest a new function for plant S6K as a repressor of cell
      proliferation and required for maintenance of chromosome stability and ploidy
      levels.

PMID- 20683444
TI  - Laminin-111: a potential therapeutic agent for Duchenne muscular dystrophy.
AB  - Duchenne muscular dystrophy (DMD) still needs effective treatments, and myoblast
      transplantation (MT) is considered as an approach to repair damaged skeletal
      muscles. DMD is due to the complete loss of dystrophin from muscles. The lack of
      link between the contracting apparatus and the extracellular matrix leads to
      frequent damage to the sarcolemma triggering muscle fiber necrosis. Laminins are
      major proteins in the extracellular matrix. Laminin-111 is normally present in
      skeletal and cardiac muscles in mice and humans but only during embryonic
      development. In this study, we showed that intramuscular injection of laminin-111
      increased muscle strength and resistance in mdx mice. We also used laminin-111 as
      a coadjuvant in MT, and we showed this protein decreased considerably the
      repetitive cycles of degeneration, inflammatory reaction, and regeneration.
      Moreover, MT is significantly improved. To explain the improvement, we confirmed
      with the same myoblast cell batch that laminin-111 improves proliferation and
      drastically increases migration in vitro. These results are extremely important
      because DMD could be treated only by the injection of a recombinant protein, a
      simple and safe therapy to prevent loss of muscle function. Moreover, the
      improvement in MT would be significant to treat the muscles of DMD patients who
      are already weak.

PMID- 20683443
TI  - Chemotherapy delivered after viral immunogene therapy augments antitumor efficacy
      via multiple immune-mediated mechanisms.
AB  - The most widely used approach to cancer immunotherapy is vaccines. Unfortunately,
      the need for multiple administrations of antigens often limits the use of one of
      the most effective vaccine approaches, immunogene therapy using viral vectors,
      because neutralizing antibodies are rapidly produced. We hypothesized that after
      viral immunogene therapy "primed" an initial strong antitumor immune response,
      subsequent "boosts" could be provided by sequential courses of chemotherapy.
      Three adenoviral (Ad)-based immunogene therapy regimens were administered to
      animals with large malignant mesothelioma and lung cancer tumors followed by
      three weekly administrations of a drug regimen commonly used to treat these
      tumors (Cisplatin/Gemcitabine). Immunogene therapy followed by chemotherapy
      resulted in markedly increased antitumor efficacy associated with increased
      numbers of antigen-specific, activated CD8(+) T-cells systemically and within the
      tumors. Possible mechanisms included: (i) decreases in immunosuppressive cells
      such as myeloid-derived suppressor cells (MDSC), T-regulatory cells (T-regs), and
      B-cells, (ii) stimulation of memory cells by intratumoral antigen release leading
      to efficient cross-priming, (iii) alteration of the tumor microenvironment with
      production of "danger signals" and immunostimulatory cytokines, and (iv)
      augmented trafficking of T-cells into the tumors. This approach is currently
      being tested in a clinical trial and could be applied to other trials of viral
      immunogene therapy.

PMID- 20683445
TI  - Prevalence of significant neoplasia in FOBT-positive patients on warfarin
      compared with those not on warfarin.
AB  - OBJECTIVES: The fecal occult blood test (FOBT) is widely used for colorectal
      cancer screening. However, the impact of warfarin use on FOBT sensitivity and
      specificity remains unclear. This study compares the relative risk of neoplasia
      in FOBT-positive patients stratified by warfarin use. METHODS: The Clinical
      Outcomes Research Initiative database was used to identify patients with positive
      FOBT as the only indication for colonoscopy during 2005-2006. Patients were
      categorized on the basis of documented warfarin status within a 30-day period
      before FOBT. We compared the demographics and prevalence of significant colon
      findings (defined as polyp >9 mm or suspected malignant tumor) among the two
      groups. After adjusting for confounding variables, logistic regression was used
      to estimate the odds ratio of significant findings in warfarin-positive vs.
      warfarin-negative patients. RESULTS: Of 10,266 patients with positive FOBT, 372
      used warfarin, 9,265 did not use warfarin, and 629 were excluded because of
      missing warfarin status. Warfarin-positive patients were more likely male (65 vs.
      50%; P<0.0001), Caucasian (88 vs. 80%; P<0.0001), and veterans (53 vs. 33%;
      P<0.0001). The prevalence of a significant finding was greater in the warfarin
      group, 16 vs. 11.4% (P<0.01). After adjusting for age and sex, the relative risk
      of significant colon findings among warfarin-positive patients was not
      significantly different from warfarin-negative patients (odds ratio 1.1, 95%
      confidence interval: 0.81-1.44). CONCLUSIONS: No increased risk for significant
      colonic findings among FOBT-positive patients according to warfarin use was
      identified. These findings suggest that continuing warfarin before FOBT will not
      affect the positive predictive value of this screening test.

PMID- 20683446
TI  - Myelosuppression by sunitinib is flt-3 genotype dependent.

PMID- 20683447
TI  - Whole blood-derived miRNA profiles as potential new tools for ovarian cancer
      screening.
AB  - BACKGROUND: Screening is an unsolved problem for ovarian cancer (OvCA). As late
      detection is equivalent to poor prognosis, we analysed whether OvCA patients show
      diagnostically meaningful microRNA (miRNA) patterns in blood cells. METHODS:
      Blood-borne whole miRNome profiles from 24 patients with OvCA and 15 age- and sex
      matched healthy controls were biostatistically evaluated. RESULTS: Student's t
      test revealed 147 significantly deregulated miRNAs before and 4 after Benjamini
      Hochberg adjustment. Although these included miRNAs already linked to OvCA (e.g.,
      miR-16, miR-155), others had never before been connected to specific diseases. A
      bioinformatically calculated miRNA profile allowed for discrimination between
      blood samples of OvCA patients and healthy controls with an accuracy of >76%.
      When only cancers of the serous subtype were considered and compared with an
      extended control group (n=39), accuracy, specificity and sensitivity all
      increased to >85%. CONCLUSION: Our proof-of-principle study strengthens the
      hypothesis that neoplastic diseases generate characteristic miRNA fingerprints in
      blood cells. Still, the obtained OvCA-associated miRNA pattern is not yet
      sensitive and specific enough to permit the monitoring of disease progression or
      even preventive screening. Microarray-based miRNA profiling from peripheral blood
      could thus be combined with other markers to improve the notoriously difficult
      but important screening for OvCA.

PMID- 20683448
TI  - Dual inhibition of EGFR and mTOR pathways in small cell lung cancer.
AB  - BACKGROUND: In this report we investigated the combination of epidermal growth
      factor receptor (EGFR) and mammalian target of rapamycin (mTOR) pathway
      inhibition as a possible new therapeutic strategy for small cell lung cancer
      (SCLC). METHODS: EGFR, p-AKT, p-ERK, p-mTOR and p-p70s6K protein expressions were
      studied by immunohistochemistry in 107 small cell lung carcinomas and correlated
      with clinicopathological parameters. Cells of SCLC were treated with erlotinib+/
      RAD001 and analysed for cell viability, proliferation, autophagy, and pathway
      regulation. RESULTS: Epidermal growth factor receptor, p-AKT, p-ERK, p-mTOR, and
      p-p70s6K were expressed in 37, 24, 13, 55 and 91% of the tumour specimens of all
      SCLC patients, respectively, and were not associated with disease-free or overall
      survival. The expression of EGFR was lower in neoadjuvant-treated patients
      (P=0.038); mTOR pathway activation was higher in the early stages of disease
      (P=0.048). Coexpression of EGFR/p-mTOR/p-p70s6K was observed in 28% of all
      patients . EGFR immunoreactivity was associated with p-ERK and p-mTOR expression
      (P=0.02 and P=0.0001); p-mTOR immunoreactivity was associated with p-p70s6K
      expression (P=0.001). Tumour cells comprised a functional EGFR, no activating
      mutations in exons 18-21, and resistance to RAD001 monotherapy. We found
      synergistic effects of erlotinib and RAD001 combination therapy on the molecular
      level, cell viability, proliferation and autophagy. CONCLUSIONS: The combined
      inhibition of EGFR/mTOR pathways could be a promising approach to treat SCLC.

PMID- 20683449
TI  - 7-O-descarbamoyl-7-hydroxygeldanamycin, a minor component from the gdmN
      disruption mutant of Streptomyces hygroscopicus 17997.

PMID- 20683450
TI  - New xanthoquinodin-like compounds, JBIR-97, -98 and -99, obtained from marine
      sponge-derived fungus Tritirachium sp. SpB081112MEf2.

PMID- 20683451
TI  - Editor's note concerning letter to the editor by DE Roth and response to letter
      to the editor by V Bhatia et al.

PMID- 20683452
TI  - Reduction of beta-amyloid deposits by gamma-secretase inhibitor is associated
      with the attenuation of secondary damage in the ipsilateral thalamus and sensory
      functional improvement after focal cortical infarction in hypertensive rats.
AB  - Abnormal beta-amyloid (Abeta) deposits in the thalamus have been reported after
      cerebral cortical infarction. In this study, we investigated the association of
      Abeta deposits, with the secondary thalamic damage after focal cortical
      infarction in rats. Thirty-six stroke-prone renovascular hypertensive rats were
      subjected to distal middle cerebral artery occlusion (MCAO) and then randomly
      divided into MCAO, vehicle, and N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S
      phenylglycine t-butyl ester (DAPT) groups and 12 sham-operated rats as control.
      The DAPT was administered orally at 72 hours after MCAO. Seven days after MCAO,
      sensory function, neuron loss, and glial activation and proliferation were
      evaluated using adhesive removal test, Nissl staining, and immunostaining,
      respectively. Thalamic Abeta accumulation was evaluated using immunostaining and
      enzyme-linked immunosorbent assay (ELISA). Compared with vehicle group, the
      ipsilateral thalamic Abeta, neuronal loss, glial activation and proliferation,
      and the mean time to remove the stimulus from right forepaw significantly
      decreased in DAPT group. The mean time to remove the stimulus from the right
      forepaw and thalamic Abeta burden were both negatively correlated with the number
      of thalamic neurons. These findings suggest that Abeta deposits are associated
      with the secondary thalamic damage. Reduction of thalamic Abeta by gamma
      secretase inhibitor may attenuate the secondary damage and improve sensory
      function after cerebral cortical infarction.

PMID- 20683453
TI  - Metabolic acidosis induced by Plasmodium falciparum intraerythrocytic stages
      alters blood-brain barrier integrity.
AB  - The pathogenesis of cerebral malaria (CM) remains largely unknown. There is
      growing evidence that combination of both parasite and host factors could be
      involved in blood-brain barrier (BBB) breakdown. However, lack of adequate in
      vitro model of human BBB so far hampered molecular studies. In this article, we
      propose the use of hCMEC/D3 cells, a well-established human cerebral
      microvascular endothelial cell (EC) line, to study BBB breakdown induced by
      Plasmodium falciparum-parasitized red blood cells and environmental conditions.
      We show that coculture of parasitized erythrocytes with hCMEC/D3 cells induces
      cell adhesion and paracellular permeability increase, which correlates with
      disorganization of zonula occludens protein 1 expression pattern. Permeability
      increase and modification of tight junction proteins distribution are
      cytoadhesion independent. Finally, we show that permeability of hCMEC/D3 cell
      monolayers is mediated through parasite induced metabolic acidosis, which in
      turns correlates with apoptosis of parasitized erythrocytes. This new coculture
      model represents a very useful tool, which will improve the knowledge of BBB
      breakdown and the development of adjuvant therapies, together with antiparasitic
      drugs.

PMID- 20683454
TI  - Recovered neuronal viability revealed by Iodine-123-iomazenil SPECT following
      traumatic brain injury.
AB  - We evaluated cortical damages following traumatic brain injury (TBI) in the acute
      phase with [(123)I] iomazenil (IMZ) single photon emission computed tomography
      (SPECT). In all, 12 patients with cerebral contusion following TBI were
      recruited. All patients underwent IMZ SPECT within 1 week after TBI. To
      investigate the changes in distribution of IMZ in the cortex in the chronic
      phase, after conventional treatment, patients underwent IMZ SPECT again. A
      decrease in the accumulation of radioligand for the central benzodiazepine
      receptor in the cortex corresponding to the contusion revealed with computed
      tomography (CT) scans and magnetic resonance imaging (MRI) were shown on IMZ
      SPECT in the acute phase in all patients. In 9 of 12 patients (75%), images of
      IMZ SPECT obtained in the chronic phase of TBI showed that areas with a decreased
      distribution of IMZ were remarkably reduced in comparison with those obtained in
      the acute phase. Both CT scans and MRI showed a normal appearance of the cortex
      morphologically, where the binding potential of IMZ recovered in the chronic
      phase. Reduced binding potential of radioligand for the central benzodiazepine
      receptor is considered to be an irreversible reaction; however, in this study,
      IMZ accumulation in the cortex following TBI was recovered in the chronic phase
      in several patients. [(123)I] iomazenil SPECT may have a potential to disclose a
      reversible vulnerability of neurons following TBI.

PMID- 20683455
TI  - Helicobacter pylori infection does not influence the efficacy of iron and vitamin
      B(12) fortification in marginally nourished Indian children.
AB  - BACKGROUND/OBJECTIVES: Helicobacter pylori infection and iron and vitamin B(12)
      deficiencies are widespread in economically disadvantaged populations. There is
      emerging evidence that H. pylori infection has a negative effect on the
      absorption of these micronutrients. The aim of this study was to evaluate the
      effect of H. pylori infection on the efficacy of micronutrient (including iron
      and vitamin B(12))-fortified foods supplied for 1 year in marginally nourished
      children. SUBJECTS/METHODS: In all, 543 Indian children, aged 6-10 years,
      participated in a double-blind, randomized controlled intervention trial,
      receiving foods fortified with either high (100% Recommended Dietary Allowances
      (RDA)) or low (15% RDA) amounts of iron, vitamin B(12) and other micronutrients.
      The presence of H. pylori infection was diagnosed by the (13)C-labeled urea
      breath test at 11 months after the start of the intervention. Blood hemoglobin,
      serum ferritin (SF), total body iron and plasma vitamin B(12) were estimated at
      baseline and 12 months, and differences between these time points were assessed
      using an independent t-test. RESULTS: Overall, the prevalence of H. pylori
      infection in this group of children was 79%. Baseline hemoglobin, SF, body iron
      and vitamin B(12) concentrations were not associated with H. pylori infection.
      The response to the intervention (either high or low amounts of iron and vitamin
      B(12) fortification) in terms of change in iron markers and vitamin B(12) status
      did not differ between children with and without H. pylori infection.
      CONCLUSIONS: This study shows that the presence of H. pylori infection did not
      affect the efficacy of long-term iron and vitamin B(12) fortification in these
      marginally nourished children.

PMID- 20683456
TI  - The effect of pre- and probiotics on the colonic ammonia metabolism in humans as
      measured by lactose-[15N2]ureide.
AB  - BACKGROUND: The evaluation of ammonia detoxification by pre- and probiotics by
      means of colonic lactose-[(15)N(2)]ureide ((15)N-LU) degradation is of great
      interest both scientifically and in terms of nutrition physiology. OBJECTIVE: Pre
      and probiotics were supplemented in healthy adults to evaluate the effect of the
      ammonia metabolism in the human colon by means of (15)N-LU. METHODS: A total of
      14 participants aged 20-28 years daily received a regular diet either without (no
      treatment) or with supplementation of 30 g fibre of potatoes (FPs), 30 g wrinkle
      pea starch (WPS, resistant starch content: 12 and 70%, respectively) and 375 g
      Lactobacillus acidophilus (LC1) yoghurt, over a 10-day period in a randomised
      order. After 1 week, 5.7 mg/kg body weight (15)N-LU was administered together
      with breakfast. A venous blood sample was taken after 6 h. Urine and faeces were
      collected over a period of 48 and 72 h, respectively. The (15)N abundances were
      measured by isotope ratio mass spectrometry. RESULTS: The mean renal (15)N
      excretion differed significantly between the supplementation of FP and no
      treatment (32.5 versus 46.3%, P=0.034), FP and LC1 (32.5 versus 51.6%, P=0.001),
      and WPS and LC1 (38.5 versus 51.6%, P=0.048). The mean faecal (15)N-excretion
      amounted to 42.7% (no treatment), 59.7% (FP), 41.8% (WPS) and 44.0% (LC1). In
      comparison with no treatment, the urinary (15)NH(3)-enrichment was significantly
      decreased at 16 h after FP supplementation. CONCLUSION: The prebiotic intake of
      FP and WPS lowered the colonic generation and the renal excretion of toxic
      (15)NH(3), respectively, when using (15)N-LU as a xenobiotic marker.

PMID- 20683457
TI  - Maternal micronutrient supplementation with zinc and beta-carotene affects
      morbidity and immune function of infants during the first 6 months of life.
AB  - BACKGROUND/OBJECTIVES: Micronutrient deficiencies are prevalent worldwide, and a
      major cause of infant death. Supplementation with multiple micronutrients during
      pregnancy might improve micronutrient status of the newborn, thereby reducing
      morbidity and death. Moreover, maternal supplementation might affect the
      newborn's immune development. Therefore, this study investigated the effects of
      maternal zinc and beta-carotene supplementation on the infant's morbidity and
      immune function during the first 6 months of life. SUBJECTS/METHODS: Mothers were
      supplemented during pregnancy with beta-carotene and/or zinc, in addition to iron
      and folic acid, in a randomized, double-blind controlled trial. Newborn infants
      (n=136) were followed up for 6 months. RESULTS: Infants born from mothers
      receiving zinc during pregnancy had significantly fewer episodes of diarrhoea
      than infants born from mothers not receiving zinc (0.2 and 0.4, respectively),
      but more episodes of cough (1.3 and 0.9 respectively) during the first 6 months.
      Maternal beta-carotene supplementation had no effect on infants' morbidity.
      Cytokine production in the newborns was affected by maternal zinc and beta
      carotene supplementation, with zinc supplementation giving higher interleukin-6
      production (16% higher), and beta-carotene supplementation leading to lower
      interferon-gamma production (36% lower). CONCLUSIONS: This study shows that
      maternal supplementation with zinc and beta-carotene affected the newborn's
      immune development in specific ways, but only maternal zinc supplementation
      significantly affected morbidity in the infants. Addition of zinc to routine iron
      and folic acid supplements for pregnant women could be an effective way to reduce
      diarrhoeal disease during the first 6 months of life, albeit at the expense of
      more episodes of cough.

PMID- 20683458
TI  - Serum levels of folate, lycopene, beta-carotene, retinol and vitamin E and
      prostate cancer risk.
AB  - Previous studies relating increased serum levels of folate and fat-soluble
      vitamins to prostate cancer risk have variously shown null associations or to
      either decrease or increase the risk of developing prostate cancer. Prospective
      studies of serum folate levels have been reported to show a null association and
      increased serum levels to either decrease or increase the risk of subsequently
      developing prostate cancer. Similarly, serum beta-carotene and lycopene levels
      have either been reported to be inversely correlated or not associated with
      prostate cancer risk. Using a prospective nested case-control study design, which
      minimized the possibility of disease effects on serum-vitamin concentrations, we
      report null associations for serum concentrations of folate, lycopene, beta
      carotene, vitamin A and vitamin E, and subsequent development of prostate cancer.

PMID- 20683459
TI  - Associations between habitual school-day breakfast consumption, body mass index,
      physical activity and cardiorespiratory fitness in English schoolchildren.
AB  - OBJECTIVES: The aim of this study was to assess associations between habitual
      school-day breakfast consumption, body mass index (BMI), physical activity (PA)
      and cardiorespiratory fitness (CRF). METHODS: BMI, PA and CRF were measured in
      4326 schoolchildren aged 10-16 years. Participants were classified as obese or
      non-obese, as having low or high PA and CRF. Habitual school-day breakfast
      consumption was assessed by a questionnaire and classified as never, sometimes or
      always. RESULTS: Participants who sometimes ate breakfast were more likely to be
      obese than those who always did (P<0.05). Boys who never ate breakfast were more
      likely to have low PA odds ratio (OR) 2.17, 95% CI 1.48-3.18) and low CRF (OR
      2.02, 95% CI 1.40-2.93) than those who always did. Compared with those who always
      did so, girls were more likely to have low PA if they sometimes (OR 1.39, 95% CI
      1.13-1.70) or never (1.48 95% CI 1.06-2.05) ate breakfast, but the likelihood of
      low CRF was not different between groups. CONCLUSIONS: Habitual breakfast
      consumption is associated with healthy BMI and higher PA levels in
      schoolchildren. In boys, regularly eating breakfast is also associated with
      higher levels of CRF. The higher PA observed in habitual breakfast eaters may
      explain the higher CRF values observed. These positive health behaviours and
      outcomes support the encouragement of regular breakfast eating in this age group.

PMID- 20683460
TI  - Major dietary patterns of young and middle aged women: results from a prospective
      Australian cohort study.
AB  - OBJECTIVE: The aim of this study was to assess the major dietary patterns of two
      age cohorts of women, to determine to the extent to which the dietary patterns
      differ between the cohorts and to assess whether they vary according to
      sociodemographic and behavioural characteristics and patterns of nutrient intake.
      METHOD: Dietary intake was assessed using an 80-item food frequency questionnaire
      for women aged 50-55 years (n=10 150; 'middle age') in 2001 and aged 25-30 years
      (n=7371; 'young') in 2003, from the Australian Longitudinal Study on Women's
      Health. Factor analysis using principal component extraction was used to identify
      dietary patterns, and a pattern score was calculated from the consumption of the
      food items identified with each dietary pattern. Associations between the dietary
      pattern scores and sociodemographic and behavioural characteristics and nutrient
      intakes were investigated using regression analysis. RESULTS: Six dietary
      patterns were identified and were labelled: cooked vegetables; fruit;
      Mediterranean-style; processed meat, meat and takeaway; reduced fat dairy; and
      high-fat and sugar foods. Regression analysis revealed that healthier dietary
      patterns were significantly associated with other favourable health-related
      behaviours, higher socioeconomic status and living in urban areas (P-values
      <0.05). CONCLUSIONS: In spite of differences in the level of consumption of
      individual food items, the similarity in dietary patterns across two generations
      of women suggests that policies and interventions to improve diet should focus on
      social and economic factors and general health-related behaviour rather than
      different age groups.

PMID- 20683461
TI  - Free fruit at workplace intervention increases total fruit intake: a validation
      study using 24 h dietary recall and urinary flavonoid excretion.
AB  - BACKGROUND/OBJECTIVES: To validate 24 h dietary recall of fruit intake by
      measuring the total 24 h excretion of 10 different flavonoids in 24 h urine
      during an intervention with free fruit at workplaces. SUBJECTS/METHODS: Employees
      at workplaces offering a free-fruit program, consisting of daily free and easy
      access to fresh fruit, and controls employees at workplaces with no free-fruit
      program were enrolled in this validation study (n=103). Dietary intake was
      assessed by using a 24 h dietary recall questionnaire at baseline and
      approximately 5 months later. Ten flavonoids, quercetin, isorhamnetin,
      tamarixetin, kaempferol, hesperetin, naringenin, eriodictyol, daidzein,
      genistein, and phloretin, were measured using HPLC-electrospray ionization-MS.
      RESULTS: The 24 h urinary excretion of total flavonoids and the estimated intake
      of fruits were significantly correlated (r (s)=0.31, P<0.01). The dietary intake
      of citrus fruits and citrus juices was significantly correlated with total
      excretion of citrus specific flavonoids (r (s)=0.28, P<0.01), and orange was
      positively correlated with naringenin (r (s)=0.24, P<0.01) and hesperetin (r
      (s)=0.24, P<0.01). Phloretin in urine was correlated with apple intake (r
      (s)=0.22, P<0.01) and also with overall estimated intake of fruit (r (s)=0.22,
      P<0.01). CONCLUSIONS: This study shows that a 24 h dietary recall can be used as
      a valid estimate of the intake of fruits in agreement with an objective biomarker
      of fruit intake in free fruit at workplace interventions.

PMID- 20683463
TI  - Intake of n-3 polyunsaturated fatty acids and non-alcoholic fatty liver disease:
      a cross-sectional study in Japanese men and women.
AB  - BACKGROUND/OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is a common
      condition, in which abnormal amounts of triglycerides accumulate in hepatocytes
      and is closely related to cardiovascular diseases and diabetes. Dietary fats
      contribute 15% of fat accumulation in the liver and regulate hepatic lipid
      metabolism. The supplementation of n-3 polyunsaturated fatty acids (n-3 PUFAs)
      improves NAFLD. The aim of this study is to assess the cross-sectional
      association between dietary n-3 PUFAs and NAFLD in Japanese men and women.
      SUBJECTS/METHODS: Participants were middle-aged, apparently healthy, 296 men and
      496 women, who did not drink alcohol and who participated in a general health
      check-up program. Dietary information from the previous month was obtained by the
      brief-type self-administered diet history questionnaire. NAFLD was diagnosed if
      abdominal ultrasonography revealed the presence of fatty liver. RESULTS: The
      prevalence of NAFLD was 45.3% in men and 17.5% in women. In comparison with the
      first tertile, multivariate adjusted odds ratios (95% confidence intervals) for
      the presence of NAFLD in the second and third tertiles for men taking
      eicosapentaenoic acid (EPA) were 0.59 (0.31-1.14) and 0.45 (0.23-0.90),
      respectively, (P for linear trend=0.024), and the multivariate adjusted odds
      ratios (95% confidence intervals) for the presence of NAFLD in the second and
      third tertiles for men taking EPA+docosahexaenoic acid (DHA) were 0.44 (0.23
      0.86) and 0.48 (0.24-0.95), respectively, (P for linear trend=0.035). However,
      there was no significant relation between NAFLD and each of these nutrients in
      women. CONCLUSIONS: Dietary EPA and EPA+DHA may be independent and preventive
      nutrients for NAFLD in Japanese men.

PMID- 20683462
TI  - Short-chain fatty acids and commensal microbiota in the faeces of severely
      malnourished children with cholera rehydrated with three different carbohydrates.
AB  - BACKGROUND: Short-chain fatty acids (SCFAs) liberated by fermentation of complex
      carbohydrates might stimulate water and salt absorption, and provide energy. The
      aim of the study was to assess the number and proportion of faecal bacteria and
      the concentration of SCFAs of severely malnourished children with cholera
      receiving oral rehydration solution (ORS) containing glucose, amylase-resistant
      starch (ARS) or rice. METHODS: Serial faecal samples were collected from 30
      malnourished children with cholera until rehydration and partial nutritional
      recovery. SCFAs were identified and quantitated by high-performance liquid
      chromatography. In situ hybridization combined with flow cytometry was used to
      analyse the microbiota in the faeces. RESULTS: Before treatment the concentration
      of total SCFA in faecal sample of cholera children was found to be 4.7+/-0.6
      mmol/kg and it increased steadily until 95.0+/-8.7 mmol/kg at day 28. Among
      different ORS groups, concentration was significantly higher in the Rice-ORS
      group at day 1 (P<0.011) and at day 2 (P<0.025). During recovery faecal output
      was significantly reduced and the number of bacteria also increased faster in the
      Rice-ORS group than in the glucose-ORS group at day 1 and day 2 (P<0.01), and a
      modest increase in bacterial number was observed in the glucose-ORS plus ARS
      group (day 1, P=0.07; day 2, P=0.09). CONCLUSION: Clinical recovery was
      associated with an increase in bacterial and SCFA concentrations with all three
      carbohydrates in ORS. However, the increases were significantly higher in
      children receiving Rice-ORS.

PMID- 20683464
TI  - Cow's milk allergy in children: adherence to a therapeutic elimination diet and
      reintroduction of milk into the diet.
AB  - BACKGROUND/OBJECTIVES: The basic treatment for cow's milk allergy (CMA) is the
      elimination of all cow's milk proteins (CMP) from the diet. This study aimed at
      characterizing the diet of children with a diagnosis of CMA, to assess the degree
      of adherence to the elimination diet and to evaluate the factors associated with
      the adherence and age of recovery. SUBJECTS/METHODS: From a birth cohort study,
      food records of 267 children diagnosed with CMA were studied to define how
      strictly the elimination diet was adhered to. Subsequent food records were
      studied to assess the age at reintroduction of milk products in the child's diet.
      RESULTS: The families adhered to the elimination diet of the child with extreme
      accuracy in 85% of the cases. Older and monosensitized children had more often
      small amounts of CMP in their diet, possibly because of the absence of
      nutritional information by a dietitian/nutritionist. Adherence to the diet was
      neither related to any other sociodemographic factor studied nor to the age at
      reintroduction of milk products into the diet. CONCLUSIONS: The therapeutic
      elimination diet of children diagnosed with CMA was well adhered to. Low intakes
      of vitamin D, calcium, and riboflavin are of concern in children who follow or
      have followed a cow's milk-free diet.

PMID- 20683465
TI  - The regular consumption of a polyphenol-rich apple does not influence endothelial
      function: a randomised double-blind trial in hypercholesterolemic adults.
AB  - BACKGROUND/OBJECTIVES: Epidemiological studies suggest that apple consumption is
      associated with a reduction in cardiovascular disease risk. Apple polyphenols may
      contribute to explain these effects. Endothelial dysfunction has been associated
      with early stage of atherosclerosis and polyphenols from various dietary sources
      have been shown to reverse it. The aim of the present study was to investigate
      the effect of the consumption of a polyphenol-rich apple on endothelial function.
      SUBJECTS/METHODS: In all, 30 hypercholesterolemic volunteers were included in a
      double-blind, randomized crossover trial. They successively consumed 40 g of two
      lyophilized apples, polyphenol-rich and polyphenol-poor, providing respectively
      1.43 and 0.21 g polyphenols per day during two 4-week periods separated by a 4
      week washout period. RESULTS: Brachial artery flow-mediated vasodilation (FMD)
      was assessed at the beginning and at the end of each intervention period. FMD did
      not differ between the polyphenol-rich and the polyphenol-poor apples, neither
      did the other cardiovascular disease risk factors (plasma lipids, homocysteine,
      antioxidant capacity). CONCLUSIONS: These data suggest that over a 4-week period,
      the consumption of a polyphenol-rich apple does not improve vascular function in
      hypercholesterolemic patients.

PMID- 20683466
TI  - The glucose signal and metabolic p[H+]lux.

PMID- 20683467
TI  - Nanog, Gli, and p53: a new network of stemness in development and cancer.

PMID- 20683468
TI  - Autophagy: a new link in the chain.

PMID- 20683469
TI  - Lord of the ring.

PMID- 20683470
TI  - Mitochondria and cell death: outer membrane permeabilization and beyond.
AB  - Mitochondrial outer membrane permeabilization (MOMP) is often required for
      activation of the caspase proteases that cause apoptotic cell death. Various
      intermembrane space (IMS) proteins, such as cytochrome c, promote caspase
      activation following their mitochondrial release. As a consequence, mitochondrial
      outer membrane integrity is highly controlled, primarily through interactions
      between pro- and anti-apoptotic members of the B cell lymphoma 2 (BCL-2) protein
      family. Following MOMP by pro-apoptotic BCL-2-associated X protein (BAX) or BCL-2
      antagonist or killer (BAK), additional regulatory mechanisms govern the
      mitochondrial release of IMS proteins and caspase activity. MOMP typically leads
      to cell death irrespective of caspase activity by causing a progressive decline
      in mitochondrial function, although cells can survive this under certain
      circumstances, which may have pathophysiological consequences.

PMID- 20683472
TI  - To err is human.

PMID- 20683473
TI  - Nucleosome sequence preferences influence in vivo nucleosome organization.

PMID- 20683474
TI  - Evidence against a genomic code for nucleosome positioning. Reply to "Nucleosome
      sequence preferences influence in vivo nucleosome organization.".

PMID- 20683471
TI  - Active DNA demethylation: many roads lead to Rome.
AB  - DNA methylation is one of the best-characterized epigenetic modifications and has
      been implicated in numerous biological processes, including transposable element
      silencing, genomic imprinting and X chromosome inactivation. Compared with other
      epigenetic modifications, DNA methylation is thought to be relatively stable.
      Despite its role in long-term silencing, DNA methylation is more dynamic than
      originally thought as active DNA demethylation has been observed during specific
      stages of development. In the past decade, many enzymes have been proposed to
      carry out active DNA demethylation and growing evidence suggests that, depending
      on the context, this process may be achieved by multiple mechanisms. Insight into
      how DNA methylation is dynamically regulated will broaden our understanding of
      epigenetic regulation and have great implications in somatic cell reprogramming
      and regenerative medicine.

PMID- 20683475
TI  - A preoccupied position on nucleosomes.

PMID- 20683476
TI  - Modeling the endoplasmic reticulum unfolded protein response.
AB  - A detailed quantitative model of signaling by IRE1 sheds light on the mechanism
      of its activation by endoplasmic reticulum stress and addresses a long-standing
      controversy in the field.

PMID- 20683477
TI  - A new nuclease member of the FAN club.
AB  - To cope with the life-threatening crisis of a DNA interstrand cross-link (ICL),
      human cells must invoke the Fanconi anemia (FA) DNA repair pathway. The FA
      pathway is a multistep repair process, requiring multiple nucleolytic incisions
      and translesion DNA synthesis. Recent work from four laboratories has identified
      a novel FA-associated nuclease, FAN1, that binds directly to monoubiquitinated
      FANCD2, resolving a decade-long puzzle regarding the function of this FANCD2
      modification.

PMID- 20683478
TI  - Kick-sTARting HIV-1 transcription elongation by 7SK snRNP deporTATion.
AB  - The HIV-1 Tat protein promotes viral transcription elongation by recruiting P
      TEFb to RNA element TAR on the viral mRNA. Recent work from D'Orso and Frankel
      uncovers unexpected aspects of this process.

PMID- 20683480
TI  - An update on regulatory T cells in transplant tolerance and rejection.
AB  - Several types of T cells with immunosuppressive properties have been identified,
      but FOXP3(+) regulatory T (T(REG)) cells have emerged as a dominant cell type;
      they are critically involved in the induction and maintenance of immune
      tolerance. Manipulation of this cell type for the induction of transplant
      tolerance including renal transplant tolerance has attracted considerable
      attention. Studies in this area have demonstrated unexpected complexities, and
      attempts to translate T(REG) cells towards clinical utility have met with
      unanticipated difficulties. In this Review, a broad overview is provided on
      recent progress in the study of T(REG) cells, focusing on challenges,
      opportunities, and emerging approaches in exploiting T(REG) cells for the
      induction of transplant tolerance.

PMID- 20683481
TI  - Are dogs genetically special?

PMID- 20683482
TI  - Power and false-positive rate in QTL detection with near-isogenic line libraries.
AB  - Libraries of near-isogenic lines (NILs) were used for quantitative trait locus
      (QTL) detection in model species and economically important crops. The
      experimental design and genetic architecture of the considered traits determine
      the statistical properties of QTL detection. The objectives of our simulation
      study were to (i) investigate the population sizes required to develop NIL
      libraries in barley and maize, (ii) compare NIL libraries with nonoverlapping and
      overlapping donor segments and (iii) study the number of QTLs and the size of
      their effects with respect to the power and the false-positive rate of QTL
      detection. In barley, the development of NIL libraries with target segment
      lengths of 10 c and marker distances of 5 cM was possible using a BC(3)S(2)
      backcrossing scheme and population sizes of 140. In maize, population sizes
      larger than 200 were required. Selection for the recipient parent genome at
      markers flanking the target segments with distances between 5 and 10 cM was
      required for an efficient control of the false-positive rate. NIL libraries with
      nonoverlapping donor chromosome segments had a greater power of QTL detection and
      a smaller false-positive rate than libraries with overlapping segments. Major
      genes explaining 30% of the genotypic difference between the donor and recipient
      were successfully detected even with low heritabilities of 0.5, whereas for minor
      genes explaining 5 !or 10%, high heritabilities of 0.8 or 0.9 were required. The
      presented results can assist geneticists and breeders in the efficient
      development of NIL libraries for QTL detection.

PMID- 20683483
TI  - Analysis of plant diversity with retrotransposon-based molecular markers.
AB  - Retrotransposons are both major generators of genetic diversity and tools for
      detecting the genomic changes associated with their activity because they create
      large and stable insertions in the genome. After the demonstration that
      retrotransposons are ubiquitous, active and abundant in plant genomes, various
      marker systems were developed to exploit polymorphisms in retrotransposon
      insertion patterns. These have found applications ranging from the mapping of
      genes responsible for particular traits and the management of backcrossing
      programs to analysis of population structure and diversity of wild species. This
      review provides an insight into the spectrum of retrotransposon-based marker
      systems developed for plant species and evaluates the contributions of
      retrotransposon markers to the analysis of population diversity in plants.

PMID- 20683484
TI  - The computer program STRUCTURE does not reliably identify the main genetic
      clusters within species: simulations and implications for human population
      structure.
AB  - One of the primary goals of population genetics is to succinctly describe genetic
      relationships among populations, and the computer program STRUCTURE is one of the
      most frequently used tools for doing so. The mathematical model used by STRUCTURE
      was designed to sort individuals into Hardy-Weinberg populations, but the program
      is also frequently used to group individuals from a large number of populations
      into a small number of clusters that are supposed to represent the main genetic
      divisions within species. In this study, I used computer simulations to examine
      how well STRUCTURE accomplishes this latter task. Simulations of populations that
      had a simple hierarchical history of fragmentation showed that when there were
      relatively long divergence times within evolutionary lineages, the clusters
      created by STRUCTURE were frequently not consistent with the evolutionary history
      of the populations. These difficulties can be attributed to forcing STRUCTURE to
      place individuals into too few clusters. Simulations also showed that the
      clusters produced by STRUCTURE can be strongly influenced by variation in sample
      size. In some circumstances, STRUCTURE simply put all of the individuals from the
      largest sample in the same cluster. A reanalysis of human population structure
      suggests that the problems I identified with STRUCTURE in simulations may have
      obscured relationships among human populations-particularly genetic similarity
      between Europeans and some African populations.

PMID- 20683485
TI  - Evolution of sex determination in C. elegans. Hidden variation mapped.

PMID- 20683486
TI  - Genetic variability at the PARK16 locus.
AB  - Parkinson's disease (PD) is a complex neurodegenerative disease which is
      clinically heterogeneous and pathologically consists of loss of dopaminergic
      neurons in the substantia nigra and intracytoplasmic neuronal inclusions
      containing alpha-synuclein aggregations known as Lewy bodies. Although the
      majority of PD is idiopathic, pathogenic mutations in several mendelian genes
      have been successfully identified through linkage analyses. To identify
      susceptibility loci for idiopathic PD, several genome-wide association studies
      (GWAS) within different populations have recently been conducted in both
      idiopathic and familial forms of PD. These analyses have confirmed SNCA and MAPT
      as loci harboring PD susceptibility. In addition, the GWAS identified several
      other genetic loci suggestively associated with the risk of PD; among these, only
      one was replicated by two different studies of European and Asian ancestries.
      Hence, we investigated this novel locus known as PARK16 for coding mutations in a
      large series of idiopathic pathologically proven PD cases, and also conducted an
      association study in a case-control cohort from the United Kingdom. An
      association between a novel RAB7L1 mutation, c.379-12insT, and disease (P
      value=0.0325) was identified. Two novel coding variants present only in the PD
      cohort were also identified within the RAB7L1 (p.K157R) and SLC41A1 (p.A350V)
      genes. No copy number variation analyses have yet been performed within this
      recently identified locus. We concluded that, although both coding variants and
      risk alleles within the PARK16 locus seem to be rare, further molecular analyses
      within the PARK16 locus and within different populations are required in order to
      examine its biochemical role in the disease process.

PMID- 20683487
TI  - Disruption of the ATP8A2 gene in a patient with a t(10;13) de novo balanced
      translocation and a severe neurological phenotype.
AB  - Mental retardation is a frequent condition that is clinically and genetically
      highly heterogeneous. One of the strategies used to identify new causative genes
      is to take advantage of balanced chromosomal rearrangements in affected patients.
      We characterized a de novo t(10;13) balanced translocation in a patient with
      severe mental retardation and major hypotonia. We found that the balanced
      translocation is molecularly balanced. The translocation breakpoint disrupts the
      coding sequence of a single gene, called ATP8A2. The ATP8A2 gene is not
      ubiquitously expressed, but it is highly expressed in the brain. In situ
      hybridization performed in mouse embryos at different stages of development with
      the mouse homologue confirms this observation. A total of 38 patients with a
      similar phenotype were screened for mutations in the ATP8A2 gene but no mutations
      were found. The balanced translocation identified in this patient disrupts a
      single candidate gene highly expressed in the brain. Although this chromosomal
      rearrangement could be the cause of the severe phenotype of the patient, we were
      not able to identify additional cases. Extensive screening in the mentally
      retarded population will be needed to determine if ATP8A2 haploinsufficiency or
      dysfunction causes a neurological phenotype in humans.

PMID- 20683488
TI  - Surgery: Are bioprosthetic plugs for complex anal fistulas effective?

PMID- 20683489
TI  - IBD: Switching metabolism-can two drugs be better than one?

PMID- 20683490
TI  - Screening: Endomicroscopy for a reliable diagnosis of colorectal neoplasia.

PMID- 20683491
TI  - Screening: Screening flexible sigmoidoscopy effective in a UK RCT.

PMID- 20683492
TI  - Bcr-abl silencing by specific small-interference RNA expression vector as a
      potential treatment for chronic myeloid leukemia.
AB  - BACKGROUND: RNA interference (RNAi) is the mechanism of gene silencing-mediated
      messenger RNA degradation by small interference RNA (siRNA), which becomes a
      powerful tool for in vivo research, especially in the areas of cancer. In this
      research, the potential use of an expression vector as a specific siRNA producing
      tool for silencing of Bcr-abl in K562 cell line has been investigated. METHODS:
      siRNA specific for Bcr-abl as short hairpin RNA (shRNA) was designed and cloned
      in expression vector (pRNAH1.1/Neo). K562 cells were cultured in RPMI media and
      transfected with shRNA expressing vector using lipofectamin 2000. Successful
      transfection was confirmed by significant increase of enhanced green fluorescent
      protein (EGFP) levels in K562-treated cells with expression vector (pEGFP-C1). In
      vitro studies in human K562 cell line entailed modulation of endogenous Bcr-abl
      mRNA levels which induced apoptosis. Effects of siRNA treatment on K562 cells
      were measured by ELISA. RESULTS: Successful expression of siRNA was confirmed by
      significant reduction of Bcr-abl mRNA levels in K562 cells treated with
      expression vector (pRNAH1.1/Neo). siRNA directed against Bcr-abl effectively
      induced apoptosis and reduced viability in human K562 cell lines. CONCLUSION:
      Expression vector of siRNA can be used in vitro to target specific RNA and to
      reduce the levels of the specific gene product in the targeted cells. Results of
      this work suggest that RNAi has potential application for the treatment of a
      variety of diseases, including those involving abnormal gene expression and viral
      contamination.

PMID- 20683493
TI  - Differential gene-expression of metallothionein 1M and 1G in response to zinc in
      sertoli TM4 cells.
AB  - BACKGROUND: Zinc (Zn) as an important trace element is essential for testicular
      development and spermatogenesis. Molecular mechanism of Zn action in the
      reproductive system may be related to metal binding low-molecular weight
      proteins, metallothioneins (MT). Our objective was to determine the effect of Zn
      on two important isoforms of MT, MT1M and MT1G genes expression on testicular
      sertoli cells. METHODS: Cultured sertoli TM4 cells were exposed to different
      concentrations of Zn at different time points. Cellular uptake of Zn was tested
      using flame atomic absorption spectrometry. The cellular viability and gene
      expression were assessed by MTT and real-time PCR methods, respectively. RESULTS:
      The treated cells resulted in higher Zn concentration and cellular viability. The
      expression of MT1M and MT1G genes in the treated cells were greater than those of
      the untreated cells (P less than 0.05). In the high dosage treated group (100 and
      500 muM), Zn concentration and expression of MT1M and MT1G genes increased three
      h after treatment; MT1G gene expression increased more at sixth h. At 18th h of
      treatment, the expression of both genes especially MT1G, increased dramatically
      while Zn concentration decreased. CONCLUSION: Since the increase of MT1G mRNA was
      coincident with cellular Zn level, it seems that MT1G has a more prominent role
      than MT1M in the homeostasis of Zn. In addition, Zn at dosage of 50 muM
      (pharmacologic concentration) may protect cells by increasing the expression of
      MT genes at longer periods.

PMID- 20683494
TI  - The effect of aspartate-lysine-isoleucine and aspartate-arginine-tyrosine
      mutations on the expression and activity of vasopressin V2 receptor gene.
AB  - BACKGROUND: Vasopressin type 2 receptor (V2R) plays an important role in the
      water reabsorption in the kidney collecting ducts. V2R is a G protein coupled
      receptor (GPCR) and the triplet of amino acids aspartate-arginine-histidine (DRH)
      in this receptor might significantly influence its activity similar to other
      GPCR. However, the role of this motif has not been fully confirmed. Therefore,
      the present study attempted to shed some more light on the role of DRH motif in G
      protein coupling and V2R function with the use of site-directed mutagenesis.
      METHODS: Nested PCR using specific primers was used to produce DNA fragments
      containing aspartate-lysine-isoleucine and aspartate-arginine-tyrosine mutations
      with replacements of the arginine to lysine and histidine to tyrosine,
      respectively. After digestion, these inserts were ligated into the pcDNA3 vector
      and transformation into E. coli HB101 was performed using heat shock method. The
      obtained colonies were analyzed for the presence and orientation of the inserts
      using proper restriction enzymes. After transient transfection of COS-7 cells
      using diethylaminoethyl-dextran method, the adenylyl cyclase activity assay was
      performed for functional study. The cell surface expression was analyzed by
      indirect ELISA method. RESULTS: The functional assay indicated that none of these
      mutations significantly altered cAMP production and cell surface expression of
      V2R in these cells. CONCLUSION: Since some substitutions in arginine residue have
      shown to lead to the inactive V2 receptor, further studies are required to define
      the role of this residue more precisely. However, it seems that the role of the
      histidine residue is not critical in the V2 receptor function.

PMID- 20683495
TI  - Cytotoxicity of subtoxic AgNP in human hepatoma cell line (HepG2) after long-term
      exposure.
AB  - We aimed at evaluating the toxicity effects of low (subtoxic) concentrations of
      silver nanoparticles nanoparticles (AgNP, 5-10 nm) in human hepatoblastoma
      (HepG2) cell line after and during a period of about one month. METHODS: XTT and
      MTT assays were used to draw a dose-response curve; IC50 (half maximal inhibitory
      concentration) value of the AgNP on HepG2 cells was calculated to be 2.75-3.0
      mg/l. The cells were exposed to concentrations of 0% (control), 1%, 4% and 8%
      IC50 of AgNP (corresponding to 0.00, 0.03, 0.12 and 0.24 mg/l of AgNP,
      respectively) for four consecutive passages. The treated cells were compared to
      the control group with respect to morphology and proliferation at the end of the
      period. RESULTS: The biochemical studies revealed significant increases of
      lactate dehydrogenase and alanine aminotransferase enzyme activity in the culture
      media of cells receiving 4% and 8% IC50; the increases in the aspartate
      aminotransferase enzyme activity and nitric oxide concentration became
      significant at 8% IC50. In the cell extracts, the average total protein and
      activity of glutathione peroxidase enzyme remained unchanged; the decrease in the
      average content of glutathione (GSH) and superoxide dismutase (SOD) activity
      became significant at 4% and 8% IC50. There were increases in lipid peroxidation
      (significant at 4% and 8% IC50) and cytochrome c content (significant at 8%
      IC50). The accumulations of the effects, during the experiment from one
      generation to the next, were not statistically remarkable except in cases of GSH
      and SOD. The results indicate clearly the involvement of oxidative changes in the
      cells after exposure to low doses of AgNP. CONCLUSION: The results might help
      specify a safer amount of AgNP for use in different applications.

PMID- 20683496
TI  - Chronic oral pelargonidin alleviates streptozotocin-induced diabetic neuropathic
      hyperalgesia in rat: involvement of oxidative stress.
AB  - BACKGROUND: Diabetes mellitus in some clinical cases is accompanied with
      hyperalgesia. In this study, we evaluated the possible beneficial effect of
      chronic pelargonidin (PG) treatment on hyperalgesia in streptozotocin (STZ)
      diabetic neuropathic rat. METHODS: Male Wistar rats (n = 56) were divided into
      seven groups, i.e. control, diabetic, PG-treated control, PG (single- and
      multiple-dose)-treated diabetic, and sodium salicylate-treated control and
      diabetics. For induction of diabetes, STZ was injected i.p. at a single dose of
      60 mg/kg. PG was orally administered at a dose of 10 mg/kg once and/or on
      alternate days for 8 weeks; 1 week after diabetes induction. After two months,
      hyperalgesia was assessed using standard formalin and hot tail immersion tests.
      Meanwhile, markers of oxidative stress in brain were measured. One-way analysis
      of variance was used for statistical analysis of the data. RESULTS: Diabetic rats
      showed a marked chemical and thermal hyperalgesia, indicating that development of
      diabetic neuropathy and PG treatment (especially multiple-doses) significantly
      ameliorated the alteration in hyperalgesia (P less than 0.05-0.01) in diabetic
      rats as compared to untreated diabetics. PG (multiple doses) also significantly
      decreased diabetes-induced thiobarbituric acid reactive substances formation and
      non-significantly reversed elevation of nitrite level and reduction of
      antioxidant defensive enzyme superoxide dismutase. CONCLUSION: These results
      clearly suggest that PG prevents diabetic neuropathic hyperalgesia through
      attenuation of oxidative stress.

PMID- 20683497
TI  - Role of estrogen receptor- alpha in an experimental model of bronchial asthma.
AB  - BACKGROUND: Use of hormone replacement therapy (HRT) may increase the risk of
      adult-onset asthma in women. Various in vitro studies have reported that
      estradiol stimulates human mast cell lines causing release of allergic mediators
      which was not observed in estrogen receptor-alpha (ER-alpha) knockout mice. Thus,
      estrogen might be a key element in occurrence of asthma. In the present study, we
      proposed to determine the role of ER-alpha in an experimental model of bronchial
      asthma. METHODS: Trypsin and egg albumin induced chronic model of asthma were
      used. On the 28th day, various parameters such as pO2 level, serum bicarbonate
      level, tidal volume, respiratory rate, air flow rate, differential white blood
      cells count in the bronchoalveolar lavage (BAL) fluid and serum cholesterol level
      were measured as well as lung histopathological examination and uterine weight
      measurement were carried out. RESULTS: Estradiol treatment resulted in lower pO2
      level, tidal volume and air flow rate. Also, serum bicarbonate level, respiratory
      rate and eosinophil rate and eosinophil count in BAL fluid were higher as
      compared to asthmatic control group. These effects were not observed in methyl
      piperidino-pyrazole (MPP) co-treated group. Histopathological data suggested that
      the destruction of alveolar and muscular layers was more prominent in estradiol
      treated group than asthmatic control and MPP co-treated groups. Estradiol-treated
      group showed lower total serum cholesterol levels and higher uterine weight as
      compared to asthmatic control group which was not observed in MPP co-treated
      group; indicating antagonism of estradiol by MPP at ER-alpha receptor.
      CONCLUSION: Estrogen seems to have a strong promoting effect on pathogenesis of
      bronchial asthma via ER-alpha receptors.

PMID- 20683498
TI  - Extracellular cholesterol oxidase from Rhodococcus sp.: isolation and molecular
      characterization.
AB  - BACKGROUND: Cholesterol oxidase (CHO) has various clinical and industrial
      applications. Recently, microbial CHO have received a great attention for their
      wide usage in medicine. Here, taxonomic characterizations of isolated strain from
      soil, optimization of the conditions for CHO production and biochemical
      characterizations of produced CHO enzyme were described. Finally, CHO gene was
      cloned into a cloning vector. METHODS: Various samples were collected and
      cultivated in a screening medium consisting of cholesterol. For isolation of CHO
      producing bacteria, well-grown colonies were inoculated into an optimized medium.
      Different biochemical and microbiological tests were performed on isolated
      bacteria to identify their properties. For phylogenic analysis, a partial
      sequence of l6s rRNA was amplified by PCR using universally conserved primers. A
      modified method was applied for determination of CHO activity. Then,
      extracellular CHO activity was assessed under different temperature, pH and
      cholesterol concentration conditions. Finally, CHO gene was amplified by PCR and
      cloned into STV28. RESULTS: According to the morphological, cultural and
      biochemical tests, the isolated bacterium was identified as Rhodococcus sp.
      strain 501 and deposited in GenBank with accession number FN298676. Results
      showed that optimum temperature and pH for CHO activity were 35 degrees C and
      7.5, respectively. Alignment of nucleotide sequence of CHO gene showed 99%
      homology with other bacterial CHO genes. CONCLUSION: Rhodococcus sp. strain 501
      produced significant levels of extracellular CHO in an optimized medium for a
      short period. CHO gene was cloned into cloning vector that can be a valuable tool
      for better identification and further studies on gene expression.

PMID- 20683499
TI  - Effects of active constituents of Crocus sativus L., crocin on streptozocin
      induced model of sporadic Alzheimer's disease in male rats.
AB  - BACKGROUND: The involvement of water-soluble carotenoids, crocins, as the main
      and active components of Crocus sativus L. extract in learning and memory
      processes has been proposed. In the present study, the effect of crocins on
      sporadic Alzheimer's disease induced by intracerebroventricular (icv)
      streptozocin (STZ) in male rats was investigated. METHODS: Male adult Wistar rats
      (n = 90 and 260-290 g) were divided into 1, control; 2 and 3, crocins (15 and 30
      mg/kg); 4, STZ; 5 and 6, STZ + crocins (15 and 30 mg/kg) groups. In Alzheimer's
      disease groups, rats were injected with STZ-icv bilaterally (3 mg/kg) in first
      day and 3 days later, a similar STZ-icv application was repeated. In STZ + crocin
      animal groups, crocin was applied in doses of 15 and 30 mg/kg, i.p., one day pre
      surgery and continued for three weeks. Prescription of crocin in each dose was
      repeated once for two days. However, the learning and memory performance was
      assessed using passive avoidance paradigm, and for spatial cognition evaluation,
      Y-maze task was used. RESULTS: It was found out that crocin (30 mg/kg)-treated
      STZ-injected rats show higher correct choices and lower errors in Y-maze than
      vehicle-treated STZ-injected rats. In addition, crocin in the mentioned dose
      could significantly attenuated learning and memory impairment in treated STZ
      injected group in passive avoidance test. CONCLUSION: Therefore, these results
      demonstrate the effectiveness of crocin (30 mg/kg) in antagonizing the cognitive
      deficits caused by STZ-icv in rats and its potential in the treatment of
      neurodegenerative diseases such as Alzheimer's disease.

PMID- 20683500
TI  - Ofatumumab in the treatment of chronic lymphocytic leukemia.
AB  - Ofatumumab is a type I fully human monoclonal antibody (IgG1) that binds to a
      unique epitope on the human CD20 molecule expressed on the surface of B cells. It
      binds specifically to both the small and large extracellular loops of the CD20
      molecule. A phase I-II study demonstrated that ofatumumab was well tolerated and
      resulted in objective responses. In a phase II study of ofatumumab in fludarabine
      and alemtuzumab-refractory chronic lymphocytic leukemia (CLL) or fludarabine
      refractory CLL with bulky (> 5 cm) lymphadenopathy, the response rates were 58%
      and 47%, respectively. This study led to accelerated approval of ofatumumab by
      the U.S. Food and Drug Administration for the treatment of CLL refractory to
      fludarabine and alemtuzumab. In a phase II study of ofatumumab with fludarabine
      and cyclophosphamide in untreated CLL, patients were randomized to ofatumumab 500
      mg (group A) or 1000 mg (group B) (initial dose, 300 mg, both groups), combined
      with fludarabine and cyclophosphamide. The higher ofatumumab dose resulted in a
      higher complete response (CR) rate (50%), compared to the lower-dose ofatumumab
      group (CR, 32%) (overall response rates, 77% and 73%, respectively). A phase III
      study of ofatumumab combined with fludarabine and cyclophosphamide versus
      fludarabine and cyclophosphamide in relapsed CLL are ongoing, as well as several
      clinical trials of ofatumumab. Ofatumumab has significant antileukemic activity
      and ongoing clinical trials will determine the role of ofatumumab in CLL.

PMID- 20683501
TI  - Paliperidone palmitate injection: Its efficacy, safety and tolerability in
      schizophrenia.
AB  - Intramuscular paliperidone palmitate is a long-acting atypical antipsychotic,
      which is currently marketed in the U.S. for the acute and maintenance treatment
      of schizophrenia in adults. Paliperidone is the active 9-hydroxy metabolite of
      risperidone. After intramuscular injection, paliperidone palmitate is slowly
      hydrolyzed to paliperidone with a mean half-life of 24-49 days, depending on the
      dose. Four randomized, double-blind, placebo-controlled trials of 9-13-weeks
      duration, demonstrated the efficacy of paliperidone palmitate (25-150 mg
      equivalents [eq.]) in improving the symptoms of acute exacerbation of
      schizophrenia. As maintenance therapy, paliperidone palmitate (25-100 mg eq.) was
      significantly more effective than placebo in delaying the time to first relapse
      in stable schizophrenia patients. Overall, paliperidone palmitate was shown to be
      well tolerated. It is available as prefilled syringes embracing a wide dose range
      (25, 50, 75, 100 and 150 mg eq.), and requires no refrigeration, reconstitution
      or oral antipsychotic supplementation.

PMID- 20683502
TI  - Pirfenidone in idiopathic pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is a progressive disease with a dismal
      prognosis for which, until recently, there were no effective treatments.
      Pirfenidone (5-methyl-1-phenylpyridin-2[1H]-one) is a novel antifibrotic agent
      that has been demonstrated to slow disease progression in patients with IPF. In
      vitro and in vivo animal models of pulmonary fibrosis have shown that pirfenidone
      exerts its effect by reducing inflammatory cytokines such as TNF-alpha, by
      downregulating the transcription of key profibrotic growth factors including TGF
      beta, and through reductions in lipid peroxidation and oxidative stress. In three
      of four multicenter, randomized, placebo-controlled trials in patients with IPF,
      pirfenidone has been shown to slow disease progression as measured by decline in
      forced vital capacity over 36-72 weeks. In general, in these clinical trials,
      pirfenidone was safe and well tolerated. Reported adverse effects include nausea,
      anorexia and photosensitivity dermatitis. A number of questions remain concerning
      the long-term efficacy and safety of pirfenidone and whether slowing of lung
      function decline will translate into improved survival for patients with IPF.
      These questions notwithstanding, pirfenidone represents an important development
      in the treatment of IPF and is a much needed addition to the previously
      inadequate therapeutic armamentarium for this devastating disease.

PMID- 20683503
TI  - Rotigotine transdermal patch for the treatment of Parkinson's disease and
      restless legs syndrome.
AB  - The nonergoline dopamine agonist rotigotine, is delivered transdermally using a
      silicone-based patch (Neupro(R); UCB Pharma GmbH), which promotes unidirectional
      drug flow from the transdermal system to the skin. Pharmacokinetic data show
      stable steady-state plasma concentrations over 24 h, maintained with once-daily
      patch administration. Stable plasma concentrations are reflected by stable
      concentrations in the brain, as has been shown in animal studies. This suggests a
      continuous stimulation of dopaminergic receptors, which may result in a reduction
      in or prevention of abnormal involuntary movements in Parkinson's disease (PD)
      after prolonged treatment. Clinical trials have demonstrated that rotigotine is
      efficacious as monotherapy for PD and restless legs syndrome (RLS), and open
      label extension studies have shown its long-term efficacy. Furthermore,
      rotigotine can be used effectively in coadministration with levodopa, enabling a
      reduction of the levodopa treatment doses in PD. Transdermal application also
      yields favorable pharmacokinetics for rotigotine: rapid metabolism and lack of
      skin accumulation allow for good control of chronic administration or withdrawal
      by patch removal, and the transdermal application approach circumvents problems
      of gastrointestinal absorption and enables administration prior to, during or
      following surgery. In addition, no dose adaptation is required regarding gender
      or ethnicity, or for patients with impaired liver or kidney function or on
      hemodialysis. The safety profile of rotigotine transdermal patch is favorable;
      common side effects attributed to transdermal delivery or dopaminergic
      stimulation are generally mild to moderate in intensity. Importantly,
      augmentation of RLS is uncommon under long-term rotigotine treatment and
      dyskinesia in PD patients mostly developed only after levodopa initiation.
      Overall, rotigotine transdermal patch has demonstrated favorable clinical
      efficacy and tolerability in the treatment of PD and RLS.

PMID- 20683504
TI  - Available and future therapies for premature ejaculation.
AB  - Premature ejaculation (PE), the most common male sexual dysfunction, impacts the
      quality of life of not only the affected male but also his partner. Despite its
      prevalence, there are currently no United States Food and Drug Administration
      approved therapies for PE. In 2004, the American Urological Association published
      treatment guidelines for PE that recommended the serotonergic antidepressants
      paroxetine, sertraline, clomipramine and fluoxetine, as well as topical lidocaine
      prilocaine cream. None of these treatments were developed for PE, and all have
      limitations associated with their use. Therapies in development may have
      advantages over the currently available treatments. These include PSD-502, a
      metered-dose aerosol of lidocaine and prilocaine used as an on-demand local
      treatment, and dapoxetine, an on-demand short-acting selective serotonin reuptake
      inhibitor. Together with a recent, evidence-based definition of PE, these novel
      therapies should improve sexual function and quality of life in men suffering
      from PE.

PMID- 20683505
TI  - Curcumin therapeutic promises and bioavailability in colorectal cancer.
AB  - Curcumin, a polyphenol and derivative of turmeric is one of the most commonly
      used and highly researched phytochemicals. Several research studies have provided
      interesting insights into the multiple mechanisms by which curcumin may mediate
      chemotherapy and chemopreventive effects on cancers, including colorectal cancer.
      Curcumin has the ability to inhibit carcinogenic promotion of colorectal cancer
      through the modulation of multiple molecular targets such as transcription
      factors, enzymes, cell cycle proteins, cell surface adhesion proteins, survival
      pathways and cytokines. A number of clinical trials dealing with curcumin's
      efficacy and safety revealed poor absorption and low bioavailability. Different
      factors contributing to the low bioavailability include low plasma level, tissue
      distribution, rapid metabolism and elimination from the body. Although, curcumin
      poor absorption and low systemic bioavailability limit its translation into
      clinics, some of the methods for its use can be approached to enhance the
      absorption and achieve a therapeutic level of curcumin. Recent clinical trials
      suggest a potential role for curcumin in regards to colorectal cancer therapy.

PMID- 20683506
TI  - A report from the 20th European Congress of Clinical Microbiology and Infectious
      Diseases (April 10-13, 2010 - Vienna, Austria).
AB  - Effective antimicrobials currently in use in Europe and throughout the world are
      fast losing ground as many pathogens acquire resistance to newly introduced
      drugs. Multidrug and panresistance have now been identified in many pathogens, as
      iteratively discussed throughout this year's meeting of the European Congress of
      Clinical Microbiology and Infectious Diseases (ECCMID). As extensively discussed
      in an oral session entitled Worldwide Dissemination of Resistances by 10
      specialists from across Europe and the world, important drug resistances have now
      been identified in Staphylococcus aureus, Streptococcus pneumoniae, Escherichia
      coli, Klebsiella pneumoniae, Salmonella enterica, Pseudomonas aeruginosa,
      Acinetobacter baumanii and virtually all known pathogens (Roede, B.M. et al.,
      Abst O127; Huenger, F. et al., Abst O395; Mera, R.M. et al., Abst O483). While
      many other issues were discussed, including the role of healthcare professionals
      and of hand hygiene in controlling the spread of infections (Derde, L. et al.,
      Abst O464), microbial resistance was indeed the main topic of discussion in the
      many oral and poster presentations at the Austria Center in Vienna. The war
      against the superbugs has been declared and initiatives have been taken for
      tracking and destroying difficult to treat pathogens. Treatments of the diseases
      caused by these multidrug- and panresistant organisms continue, as manifested by
      new research and population surveys. However, with antimicrobial resistances as
      leitmotiv background music, other very recent scientific achievements and
      findings in diagnostics and treatment for infectious diseases took center stage
      in Vienna, including important information on novel drugs for infectious diseases
      and the use and comparative effectiveness of extant drugs, as summarized in the
      following report.

PMID- 20683510
TI  - Solvothermal syntheses, structures, and physical properties of four new
      coordination compounds constructed from a bent dicarboxylate ligand.
AB  - Four new coordination compounds, namely {[Cd(3)(L)(2)(mu(3)-OH)(2)(H(2)O)] x
      H(2)O}(n) (1), {Ni(L)(bipy)}(n) (2), {Cu(3)(L)(2)(bipy)(mu(2)-OH)(2)(DMF)(2)}(n)
      (3), and {Co(2)L(2)(H(2)L)(H(2)O)}(n) (4), have been synthesized by the
      solvothermal reaction of 4,4'-(hexafluoroisopropylidene)bis(benzoic acid) (H(2)L)
      with different transition metal ions in the presence of co-ligand 4,4'-bipyridine
      (bipy). Compound 1 displays a three-dimensional (3D) framework containing
      infinite bands constructed of heptanuclear cadmium clusters. In compound 2,
      [Ni(2)C(2)O(4)] secondary building units (SBUs) are linked by L(2-) ligands into
      a 1D ribbon, which are further assembled into a two-dimensional (2D) non
      interpenetrated structure with {4(4) x 6(2)} topology. Compound 3 possesses a 3D
      framework with a new topology of {4(3)}(2){4(6) x 6(14) x 8(8)} net, while the
      structure of 4 is a duplicate interpenetrated 3D framework with {4(12) x 6(3)}
      net. Temperature-dependent magnetic studies reveal that 3 exhibits ferromagnetic
      coupling between adjacent Cu(II) ions. The photoluminescent property of 1 has
      been studied in the solid state at room temperature.

PMID- 20683511
TI  - Dichloromethane as solvent for the synthesis of polycationic clusters at room
      temperature--a link to standard organometallic chemistry.
AB  - Dichloromethane (DCM), CH(2)Cl(2) has been identified as an alternative reaction
      medium for room-temperature synthesis of subvalent homopolyatomic clusters of the
      group 15 element bismuth.

PMID- 20683512
TI  - Fluorescence of sanguinarine: spectral changes on interaction with amino acids.
AB  - The quaternary isoquinoline alkaloid, sanguinarine (SG) exhibits a wide range of
      biological activities. This study examines spectral changes expected from SG
      binding to proteins. Fluorescence spectra of the cationic form of sanguinarine
      (SG(+)) are sensitive to environment polarity. On the other hand, spectra of the
      neutral form of sanguinarine, pseudobase (SGOH) and dihydrosanguinarine (DHSG,
      the first metabolite of SG) exhibit higher sensitivity to the ability of solvent
      to form a solute-to-solvent hydrogen bonds. Interaction with cysteine has been
      the only mode of SG binding to enzymes that has been considered so far. In
      reality, our experiments have revealed spectral changes on specific interactions
      of SG(+) with Cys, Glu and Tyr in the protic environment and with Arg and Glu in
      the aprotic environment. We have also detected interactions of SGOH with Cys in
      the protic environment and with Cys, Glu and Lys in the aprotic environment. The
      DHSG spectra were only altered in the presence of the Cys analog in the protic
      environment. We have also demonstrated that spectral change analysis can aid
      investigation of SG/DHSG interactions with proteins and we were able to identify
      SG(+)-binding site on Na(+)/K(+)-ATPase.

PMID- 20683513
TI  - The keto/enol tautomerism in acetoacetyl fluoride: properties, spectroscopy, and
      gas-phase and crystal structures of the enol form.
AB  - Tautomeric properties of acetoacetyl fluoride, CH(3)-C(O)-CH(2)-C(O)-F, were
      studied by IR (gas phase), Raman (liquid and solid), and NMR spectroscopy (neat
      liquid), gas electron diffraction (GED), X-ray crystallography, and quantum
      chemical calculations. The keto-enol tautomer possesses a much higher vapour
      pressure than the diketo form and therefore the keto-enol form strongly
      predominates in the gas phase. In the neat liquid state the thermally unstable
      compound tautomerizes at low temperatures slowly to yield the diketo form. Raman
      and NMR spectra show equilibrium with strong predominance of the diketo tautomer
      (>90%) in the liquid phase. Single crystals, grown at -90  degrees C from the gas
      phase, contain exclusively acetoacetyl fluoride in the keto-enol form and the
      molecules possess a planar skeleton with overall C(S) symmetry and with the O-H
      bond adjacent to the methyl group.

PMID- 20683514
TI  - The onset of molecular condensation: hydrogen.
AB  - The very first steps of condensation as studied experimentally in the simplest
      molecular system (para-H(2)) are reported. The fast time-space evolution of the
      nascent clusters have been measured using state-of-the-art Raman spectroscopy
      implemented on cryogenic supersonic jets. The time-dependent onset of
      condensation is presented in a non-equilibrium pressure-temperature phase
      diagram. Dimer and trimer formation are found to obey three-body processes whose
      rates have been determined.

PMID- 20683515
TI  - Some fundamental properties and reactions of ice surfaces at low temperatures.
AB  - Ice surfaces offer a unique chemical environment in which reactions occur quite
      differently from those in liquid water or gas phases. In this article, we examine
      the basic properties of ice surfaces below the surface premelting temperature and
      discuss some of the recent investigations carried out on reactions at the ice
      surfaces. The static and dynamic properties of an ice surface as a reaction
      medium, such as its structure, molecule diffusion and proton transfer dynamics,
      and the surface preference of hydronium and hydroxide ions, are discussed in
      relation to the reactivity of the surface.

PMID- 20683516
TI  - A comparative IR characterization of acidic sites on HY zeolite by pyridine and
      CO probes with silica-alumina and gamma-alumina references.
AB  - Using IR spectroscopy, three different surface states of HY zeolite were probed
      by successive adsorption of CO at 143 K followed by evacuation and pyridine
      adsorption at 523 K: HY zeolite [1] without strong Lewis acid sites (LAS); [2]
      after high temperature (873 K) evacuation to convert Bronsted acid sites (BAS) to
      strong LAS; and [3] after water re-adsorption on HY zeolite [2] to recover BAS
      from LAS. The original surface of HY zeolite [1] seemed to be recovered on HY
      zeolite [3] after high temperature evacuation and water treatment by CO
      adsorption, while a part of generated LAS on HY zeolite [2] seemed irreversible
      on HY zeolite [3] to HY zeolite [1] by pyridine adsorption. To clarify this
      discrepancy, re-examination of the IR spectra of adsorbed CO and pyridine on
      gamma-alumina and silica-alumina after similar treatments to those on HY zeolite
      was conducted. Based on the results of CO adsorption on gamma-alumina and silica
      alumina, the presence of extra-framework aluminium sites on HY zeolite [1] was
      confirmed. High temperature evacuation of HY zeolite [1] formed very strong LAS,
      a part of which was irreversible to BAS by water re-adsorption at room
      temperature. The irreversible sites on HY zeolite [3] were assigned to non-acidic
      OH groups attributed to silica-alumina. The non-acidic OH groups on HY zeolite
      [3], which were BAS on HY zeolite [1], hydrogen-bonded to pyridine to show IR
      spectra similar to those adsorbed on LAS. Thus, LAS on HY zeolite [3] seemed
      irreversible by pyridine adsorption after water re-adsorption. On the other hand,
      CO adsorbed on non-acidic OH groups showed a band at only slightly lower
      frequency (2160 cm(-1)) than that of BAS (2178 cm(-1)), resulting in overlapps
      and ignoring their presence. Thus, CO adsorption seemed to show that complete
      recovery of LAS to BAS occurred.

PMID- 20683517
TI  - Long-range electron transfer in recombinant peroxidases anisotropically
      orientated on gold electrodes.
AB  - Long-range electron transfer (ET) in horseradish peroxidase (HRP) was studied
      with a wild-type recombinant form of HRP, rHRP, and recombinant forms containing
      histidine and cysteine tags at Gln1, Asn57, Asn189, or Ser309 amino acid residues
      of the protein. Chemisorption of the enzyme onto the Au electrodes through the
      tags introduced in different positions of the protein surface provided
      anisotropic orientations of the rHRPs on the Au surface, which allowed a
      restricted "rotation" of the rHRP molecules on the electrodes. Atomic force
      microscopy (AFM) studies revealed the monolayer coverage of the enzyme on gold
      surfaces and the specific orientations of different forms of rHRP, which may be
      characterized by different distances between the heme active site of rHRP and the
      gold electrode. The efficiency of long-range ET between the electrode and the
      heme of rHRP was estimated from direct non-catalytic electrochemistry of rHRPs
      differently orientated on Au and compared with the theoretically calculated
      values from the protein ET model (C. C. Page, C. C. Moser, X. Chen, P. L. Dutton,
      Nature, 1999, 402, 47-51), under the assumption that ET occurs within the protein
      structure between the heme and the tag-modified amino acid residue of the
      protein. Comparative analysis of the long-range ET through the rHRP showed that
      the highest ET rates, obtained for the rHRP forms containing the tags at C- or N
      termini of the enzyme, did not correlate with the shortest ET distance, but were
      instead consistent with the directional ET along the most favourable ET pathway
      within the protein matrix.

PMID- 20683518
TI  - Facile glycosylation strategy with two-stage activation of allyl glycosyl donors.
      Application to concise synthesis of Shigella flexneri serotype Y O-antigen.
AB  - A practical, useful glycosylation method employing only allyl glycoside building
      blocks has been developed. The donor's glycosylation reactivity is turned on via
      isomerization of its anomeric allyl protecting group into the corresponding prop
      1-enyl moiety. Subsequent chemoselective activation with NIS/TfOH achieves high
      yields in glycosidic bond construction at room temperature. The efficacy and
      efficiency of this approach in carbohydrate synthesis is demonstrated in the
      concise synthesis of the fully protected Shigella flexneri serotype Y O-antigen.

PMID- 20683519
TI  - Reversible conformational change of cytochrome c at a modified gold electrode in
      methanol.
AB  - Changes in the secondary structure of cytochrome c on immersion in methanol were
      monitored using circular dichroism. These changes occurred immediately in
      methanol, upon re-immersion in aqueous buffer, the secondary structure was
      restored in ca. 45 min. This method enables the secondary structure of proteins
      in non-aqueous solvents to be monitored in real time.

PMID- 20683520
TI  - Organosoluble polypyrrole nanotubes from core-shell bottlebrush copolymers.
AB  - Well-defined, organosoluble polypyrrole nanotubes were synthesized by single
      molecule templating of multicomponent bottlebrush copolymers with triblock
      terpolymer side chains.

PMID- 20683521
TI  - Water-induced reversible structural phase transformation with chromotropism in
      metal supramolecular frameworks containing aminopyrazine and sulfate anions.
AB  - Three new supramolecular metal-coordination architectures
      [M(H2O)4(ampyz)2][M(H2O)6](SO4)2(H2O)2 (M = Co (1), Fe (2), and mixed Co/Fe (3);
      ampyz = 2-aminopyrazine) and a Cd(II) coordination polymer
      [Cd(ampyz)(H2O)2(SO4)]n(H2O)n (4) were synthesized by layered diffusion and
      structurally characterized. Compounds 1-3 are isomorphous. Monomeric complex
      units [M(H2O)4(ampyz)2]2+ are assembled by intermolecular hydrogen bonding and pi
      pi stacking via ampyz moieties to build 2D sheets. These layers are linked by
      intermolecular hydrogen bonding via ampyz ligand, [M(H2O)6]2+ unit, sulfate anion
      and lattice and coordinated water molecules to stabilize 3D supramolecular
      structure. Compound 4 shows a 2D coordination network where the sulfato connector
      and the bridging ampyz link Cd(II) ions. Lattice water molecules are filled in
      between the layers via the hydrogen bonds stabilizing 3D supramolecular network
      of 4. Interestingly, compounds 1-3 exhibit water-induced reversible crystal-to
      amorphous transformations with chromotropism and compound 4 also shows water
      induced reversible structural phase transformation confirmed by spectroscopic
      techniques, elemental analyses, TGA, and XRPD. These results demonstrate the
      significant role between coordination bridges and weaker intermolecular
      interactions for the structural conversion even though 1-3 lack coordination
      bridges for the maintenance of their structures, however, the weak intermolecular
      interactions, especially hydrogen bonding, play a key role to the recovery of the
      crystalline phase.

PMID- 20683522
TI  - Rapid quantification of melamine in milk using competitive 1,1'-oxalyldiimidazole
      chemiluminescent enzyme immunoassay.
AB  - A novel competitive 1,1'-oxalyldiimidazole (ODI) chemiluminescent enzyme
      immunoassay (CLEIA) was developed as a method for rapid and simple screening of
      melamine in milk. Fat existing in milk acts as an inhibitor in the competitive
      binding interaction of melamine and anti-melamine in the presence of melamine
      conjugated horseradish peroxidase. Thus, the calibration curve and sensitivity of
      competitive ODI CLEIA for the quantification of melamine in fat free milk were
      wider and better than those in milk containing fat. However, a centrifuge is not
      a good method for removing the inhibitor because a portion of the melamine is
      also removed with the fat. The incubation time (20 min) for the competitive
      binding interaction of anti-melamine and melamine in 20% milk diluted with PBS
      buffer of pH 7.4 was longer than that (10 min) in 100% milk even though the
      sensitivity of the former was better than latter. The limit of detection (1.12
      ppb) determined in rapid ODI CLEIA (dynamic range: 3.8-125 ppb) for the
      quantification of melamine in 20% milk not containing fat was lower than those
      (6.3 and 9.0 ppb) calculated in relatively time-consuming luminol CLEIA and
      enzyme-linked immunosorbent assay (ELISA). Also, we expect that ODI-CLEIA
      (dynamic range: 62.5-2000 ppb) capable of directly quantifying melamine in 100%
      milk without any pretreatment can be applied as a new and simple method for rapid
      screening of melamine in milk.

PMID- 20683523
TI  - Tailored synthesis of mesoporous platinum replicas using double gyroid mesoporous
      silica (KIT-6) with different pore diameters via vapor infiltration of a reducing
      agent.
AB  - We demonstrate facile synthesis of mesoporous Pt replicas using double gyroid
      mesoporous silica (KIT-6) with different pore diameters via vapor infiltration of
      a reducing agent. Through controlling the complementary pore size, it becomes
      possible to selectively deposit Pt into one side pore of the Ia3d bicontinuous
      structure, thereby forming a mesoporous Pt replica with relatively large
      mesopores (over 10 nm).

PMID- 20683525
TI  - Catalytic properties of a series of coordination networks: cyanosilylation of
      aldehydes catalyzed by Zn(II)-4,4'-bpy-carboxylato complexes.
AB  - Three porous crystalline coordination polymers, i.e. the three-dimensional
      framework {[Zn(3)(4,4'-bpy)(3.5)(mu
      O(2)CH)(4)(H(2)O)(2)](ClO(4))(2)(H(2)O)(2)}(n) (1), the one-dimensional three-leg
      ladder {[Zn(3)(4,4'-bpy)(3)(mu-O(2)CCH(3))(4)(H(2)O)(2)](PF(6))(2)(H(2)O)(2)}(n)
      (2), and the two-dimensional layered network {[Zn(3)(4,4'-bpy)(4)(mu
      O(2)CCH(2)CH(3))(4)](ClO(4))(2)(4,4'-bpy)(2)(H(2)O)(4)}(n) (3), have been
      investigated. All networks exhibit voids that contain the counter-ions and guest
      molecules, namely water for compounds 1 and 2, and water/4,4'-bpy for compound 3.
      In addition, compounds 2 and 3 are further stabilized by hydrogen bonds and pi-pi
      stacking interactions to form intricate supramolecular frameworks. The removal
      and reintroduction of guest water molecules for compounds 2 and 3 have been
      explored for their dynamic structural transformation. Interestingly, all Zn(II)
      compounds are active heterogeneous catalysts for the high-yield cyanosilylation
      of acetaldehydes in dichloromethane.

PMID- 20683524
TI  - Multicolored redox active upconverter cerium oxide nanoparticle for bio-imaging
      and therapeutics.
AB  - Cytocompatible, co-doped cerium oxide nanoparticles exhibited strong upconversion
      properties that were found to kill lung cancer cells by inducing apoptosis
      thereby demonstrating the potential to be used as clinical contrast agents for
      imaging and as therapeutic agents for treatment of cancer.

PMID- 20683526
TI  - Tailoring microstructures of isopolymolybdates: regular tuning of the ligand
      spacer length and metal coordination preferences.
AB  - Four new isopolymolybdate compounds based on two kinds of isomers,
      [Cu(I)(2)bte][a-Mo(3)O(10)] (1), [Cu(I)(2)btp][b-Mo(3)O(10)].H(2)O (2),
      [Cu(II)(bte)(1.5)(H(2)O)][gamma-Mo(8)O(26)](0.5) (3) and
      [Cu(II)(btp)(2)(H(2)O)][beta-Mo(8)O(26)](0.5).2H(2)O (4) [bte = 1,2-bis(1,2,4
      triazol-1-yl)ethane, btp = 1,3-bis(1,2,4-triazol-1-yl)propane], were obtained
      under hydrothermal conditions, indicating that isopolymolybdate clusters can be
      tailored by regular tuning of the spacer length of the flexible ligands and the
      metal coordination preferences. In compound 1, wave-like a-[Mo(3)O(10)](2-)
      chains intersect with [Cu(I)(2)bte](2+) chains by sharing Cu(I) cations, forming
      a 3D framework. Compound 2, with a similar 3D structure but different ligand
      (btp) to 1, is based on linear b-[Mo(3)O(10)](2-) chains. In compound 3, gamma
      [Mo(8)O(26)](4-) chains insert into the rectangular windows of parallel
      [Cu(II)(2)bte](4+) sheets and connect them via four Cu(II)-O bonds, leading to a
      3D framework. Compound 4 is an unusual 2D-->3D polycatenated array of a
      [Cu(II)(btp)(2)(H(2)O)][beta-Mo(8)O(26)] pillar-layered framework. The thermal
      stability and luminescent properties of compounds 1-4 were investigated in the
      solid state.

PMID- 20683527
TI  - Grafting of peralkylated Ln(II)Al(III) heterobimetallic complexes onto periodic
      mesoporous silica KIT-6.
AB  - Tetraethylaluminates of the divalent lanthanides ytterbium and samarium were
      grafted onto large-pore cubic periodic mesoporous silica (PMS) KIT-6, which had
      been dehydroxylated at 500 degrees C (specific surface area a(s): 500 m(2)g(-1);
      mesopore volume V(p): 1.06 cm(3)g(-1); main pore diameter: 85 A). The bimetallic
      materials [Ln(AlEt(4))(2)]@KIT-6(-500) were analysed by DRIFT spectroscopy,
      elemental analysis, nitrogen physisorption and solid-state NMR. Upon
      heterogenization the surface area and pore volume of the KIT-6 materials dropped
      by 30-35% and 25%, respectively. The hybrid materials were compared to
      AlEt(3)@KIT-6(-500) since reaction of AlEt(3) with surface silanol groups is also
      a prominent reaction pathway when complexes [Ln(AlEt(4))(2)](n) are immobilized.
      Reaction of the Ln(II) tetraalkylaluminates with tris(tert-butoxy)silanol
      HOSi(OtBu)(3) gave complexes Ln[(mu-OSi(OtBu)(3))(mu-R)AlR(2)](2) (Ln = Yb, Sm; R
      = Et; Ln = Yb; R = Me) which can be seen as molecular model complexes, evidencing
      alkane elimination, trialkylaluminium adduct formation, and Ln(II)-O(siloxane)
      bonding.

PMID- 20683528
TI  - Electrogenerated chemiluminescence determination of C-reactive protein with
      carboxyl CdSe/ZnS core/shell quantum dots.
AB  - Electrogenerated chemiluminescence (ECL) of water-soluble core/shell CdSe/ZnS
      quantum dots (QDs) coated with carboxylated polyethylene glycol polymers ("Qdot
      625") was investigated in aqueous solutions using 2-(dibutylamino)ethanol (DBAE)
      and tri-n-propylamine (TPrA) as ECL coreactants. In both cases, ECL emissions at
      glassy carbon (GC) electrode appeared at the same potential of approximately 0.80
      V vs. Ag/AgCl (3.0 M KCl), which was approximately 200 and approximately 150 mV
      more positive compared with the oxidation potentials for DBAE (approximately
      +0.60 V vs. Ag/AgCl) and TPrA (approximately +0.65 V vs. Ag/AgCl), respectively.
      The ECL intensity, however, was significantly affected by the type and the
      concentration of the ECL coreactant used as well as the nature of the working
      electrode. Under the present experimental conditions, ECL from DBAE was
      approximately 17 times stronger than that from TPrA. The maximum ECL was obtained
      at GC electrode when [DBAE] approximately = 53 mM, where a ratio of 11:3:1 in ECL
      intensity was evaluated for GC, Au, and Pt electrodes, respectively. The ECL
      emission of the Qdot 625/DBAE system had an apparent peak value of approximately
      625 nm that matched well the fluorescence data. The QD as a label for ECL-based
      immunoassays of C-reactive protein (CRP) was realized by covalent binding of
      avidin on its surface, which allowed biotinylated anti-CRP to be attached and
      interacted with solution-phase CRP and the anti-CRP linked to micro-sized
      magnetic beads. The newly formed sandwich type aggregates were separated
      magnetically from the solution matrix, followed by the ECL generation at
      partially transparent Au nanoparticle-coated ITO electrode or Au/CD electrode in
      the presence of DBAE. Much stronger ECL responses were observed from the Au/CD
      electrode, at which a dynamic range of 1.0-10.0 microg mL(-1) CRP and a limit of
      detection of 1.0 microg mL(-1) CRP were obtained, respectively.

PMID- 20683529
TI  - Enzyme mediated silicon-oxygen bond formation; the use of Rhizopus oryzae lipase,
      lysozyme and phytase under mild conditions.
AB  - The potential for expanding the variety of enzymic methods for siloxane bond
      formation is explored. Three enzymes, Rhizopus oryzae lipase (ROL), lysozyme and
      phytase are reported to catalyse the condensation of the model compound,
      trimethylsilanol, formed in situ from trimethylethoxysilane, to produce
      hexamethyldisiloxane in aqueous media at 25  degrees C and pH 7. Thermal
      denaturation and reactant inhibition experiments were conducted to better
      understand the catalytic role of these enzyme candidates. It was found that
      enzyme activities were significantly reduced following thermal treatment,
      suggesting a potential key-role of the enzyme active sites in the catalysis.
      Similarly, residue-specific modification of the key-amino acids believed to
      participate in the ROL catalysis also had a significant effect on the silicon bio
      catalysis, indicating that the catalytic triad of the lipase may be involved
      during the enzyme-mediated formation of the silicon-oxygen bond. E. coli phytase
      was found to be particularly effective at catalysing the condensation of
      trimethylsilanol in a predominantly organic medium consisting of 95% acetonitrile
      and 5% water. Whereas the use of enzymes in silicon chemistry is still very much
      a developing and frontier activity, the results presented herein give some
      grounds for optimism that the variety of enzyme mediated reactions will continue
      to increase and may one day become a routine element in the portfolio of the
      synthetic silicon chemist.

PMID- 20683530
TI  - Effects of the silicon core structures on the hole mobility of star-shaped
      oligothiophenes.
AB  - Star-shaped compounds with three or four oligothiophene units linked by an
      organosilicon core were prepared and their hole-transport capabilities were
      studied. A top-contact type thin film transistor (TFT) with a vapour-deposited
      film of tris[(ethylterthiophenyl)dimethylsilyl]methylsilane (3T(3)Si(4)) showed
      field-effect mobility (MU(FET)) of 4.4 * 10(-5) cm(2) V(-1) s(-1), while the
      device with the carbon centred analogue
      tris[(ethylterthiophenyl)dimethylsilyl]methane (3T(3)Si(3)C) showed no TFT
      activity. Intrinsic intramolecular hole mobility of 3T(3)Si(4) and 3T(3)Si(3)C
      was determined by time-resolved microwave conductivity measurements to be 8 * 10(
      2) and 2 * 10(-2) cm(2) V(-1) s(-1), respectively, arising from higher degree of
      sigma-pi interaction in 3T(3)Si(4). To know more about the effects of the
      organosilicon core structures on the intermolecular hole mobility, we calculated
      internal reorganization energies for hole transfer at the (U)B3LYP/6
      311+G(d,p)//(U)B3LYP/6-31G(d) level, which suggested smoother intermolecular
      charge transfer in the silicon derivative than the carbon and germanium
      analogues. Star-shaped compounds with quarterthiophene units behave in a
      different manner from the terthiophene derivatives and
      tris[(ethylquarterthiophenyl)dimethylsilyl]methane (4T(3)Si(3)C) showed higher
      TFT mobility of MU(FET) = 1.2 * 10(-3) cm(2) V(-1) s(-1) than its silicon
      analogue (4T(3)Si(4): MU(FET) = 5.4 * 10(-4) cm(2) V(-1) s(-1)). This is probably
      due to the more condensed packing of 4T(3)Si(3)C in the film, arising from the
      shorter Si-C bonding. Compounds with four terthiophene units were also prepared
      and tetrakis[(ethylterthiophenyl)-dimethylsilyl]silane (3T(4)Si(5)) showed the
      mobility of MU(FET) = 2.0 * 10(-4) cm(2) V(-1) s(-1), higher than that of
      3T(3)Si(4), indicating the potential of tetrakis(oligothiophenyl) compounds as
      the TFT materials. Tetrakis[(ethylterthiophenyl)dimethylsilyl]germane
      (3T(4)Si(4)Ge) was less thermally stable and could not be processed to a film by
      vapour-deposition, but was found to be TFT active in the spin-coated film,
      although the mobility was rather low (MU(FET) = 7.7 * 10(-7) cm(2) V(-1) s(-1)).

PMID- 20683531
TI  - DNA cleavage by the Cu(II) complex of the DNA-intercalating 9-bis(pyridin-2
      ylmethyl)aminobenzo[b]quinolizinium.
AB  - The synthesis and the investigation of the Cu(II)-binding, the DNA-binding, and
      the DNA-damaging properties of a conjugate between the benzo[b]quinolizinium ion
      and the bis(pyridin-2-ylmethyl)amino receptor are presented. Photometric and
      fluorimetric titrations as well as CD spectroscopic analysis reveal that the 9
      bis(pyridin-2-ylmethyl)aminobenzo[b]quinolizinium ligand intercalates into DNA
      (K(b) = 1.9 x 10(4) M(-1)) and exhibits a high selectivity towards complexation
      of Cu(2+) in water (K(b) = 4.3 x 10(4) M(-1)). This combination of
      functionalities allows to localize Cu(2+) in close proximity of DNA, where these
      metal ions induce efficient DNA damage, as shown by the single-strand cleavage of
      supercoiled plasmid DNA. Notably, the DNA cleavage does not require additional
      reagents nor light.

PMID- 20683532
TI  - Syntheses, crystal structures, and properties of three new lanthanum(III)
      vanadium iodates.
AB  - Systematic explorations of new compounds in the La(3+)-V(4+)/V(5+)-iodate system
      led to three new lanthanum(III) vanadium iodates, namely, LaVO(IO(3))(5),
      LaV(2)O(6)(IO(3)), and LaVO(2)(IO(3))(4).H(2)O. LaVO(IO(3))(5) is isostructural
      with LaTiO(IO(3))(5) and its structure contains a 0D [VO(IO(3))(5)](3-) anionic
      unit composed of one VO(6) octahedron linked to five IO(3)(-) groups. Such 0D
      anionic units are separated by La(3+) ions. LaV(2)O(6)(IO(3)) exhibits a unique
      3D framework composed of 1D [V(2)O(6)](2-) ladder like chains and 2D
      [La(IO(3))](2+) layers. LaVO(2)(IO(3))(4).H(2)O is isostructural with
      LnMoO(2)(IO(3))(4)(OH) (Ln = La, Nd, Sm, Eu) with a polar space group P2(1), its
      structure contains a novel 0D [VO(2)(IO(3))(4)](3-) anionic unit composed of one
      VO(6) octahedron linked with four IO(3)(-) groups and two terminal O(2-) anions.
      Such 0D anionic units are separated by La(3+) ions. The structure of
      LaVO(2)(IO(3))(4).H(2)O can also be described as the 8-MR channels of the 3D
      [La(IO(3))(4)](-) anion being filled by the VO(6) octahedra and lattice water
      molecules. LaVO(2)(IO(3))(4).H(2)O displays a weak SHG response of about 0.2
      times that of KDP. Optical, thermal stability and magnetic susceptibility
      measurements as well as theoretical calculations have also been performed.

PMID- 20683533
TI  - Asymmetric trimethine 3H-indocyanine dyes: efficient synthesis and protein
      labeling.
AB  - We present an efficient method to synthesize three new asymmetric trimethine
      cyanine dyes containing only one carboxylic acid group for bioconjugation. Two of
      them have better protein labeling performance than other conventional cyanine
      dyes due to their particular structure design.

PMID- 20683534
TI  - Stereospecific and highly stereoselective cyclopropanation reactions promoted by
      samarium.
AB  - Samarium metal and samarium diiodide have become important tools as selective
      cyclopropanating agents in organic synthesis due to their high chemo- and
      stereoselectivity. Therefore, Sm and SmI(2) are the ideal reagents to prepare
      cyclopropane derivatives. This tutorial review highlights C-C multiple bond
      cyclopropanation processes promoted by samarium or samarium diiodide.

PMID- 20683535
TI  - The first unpaired electron placed inside a C3-symmetry P-chirogenic cluster.
AB  - The Pd(3)(dppm*)(3)(CO)(n+) enantiomers (n = 2 (2), 1 (3)) were prepared either
      from (R,R)- or (S,S)-P-chirogenic bis(phenyl-m-xylylphosphino)methane (dppm*; 1)
      and Pd(OAc)(2) in the presence of CF(3)CO(2)H, CO and water (n = 2), and then by
      reductive electrolysis (n = 1). The stable enantiomeric [Pd(3)((S,S)
      dppm*)(3)(CO)](+) (3), is the first C(3)-symmetry radical-cation M-M bonded
      cluster, therefore the odd electron is delocalized onto the Pd(3) frame within
      this symmetry. The novel chiral species have been characterized by circular
      dichroism (CD) of both enantiomers of the Pd(3)(dppm*)(3)(CO)(2+) clusters (2)
      and by EPR spectroscopy for the Pd(3)((S,S)-dppm*)(3)(CO)(+) paramagnetic
      compounds (3, g = 2.041). Evidence for reduced symmetry with respect to the
      achiral cluster was also obvious from the hyperfine splittings of the EPR signal
      which display three different hyperfine coupling values: 3 *A((31)P) = 83.9 * 10(
      4) cm(-1), 3 *A((31)P) = 69.7 * 10(-4) cm(-1), 3 *A((105)Pd) = 12.5 * 10(-4) cm(
      1). In the absence of an X-ray structure for the paramagnetic clusters, DFT
      computations were performed to address the geometry. The optimized geometry of
      the Pd(3)((S,S)-dppm*)(3)(CO)(+) radicals (3) exhibits three phosphorus atoms
      placed well above the Pd(3) plane, while the three others are located below the
      trimetallic frame within C(3)-symmetry due to intramolecular steric hindrance.
      This makes them chemically different with respect to the carbonyl group and
      explains the experimental EPR spectrum well. Consequently this C(3)-symmetry
      deformation also induces a change in the shape of the SOMO (semi-occupied
      molecular orbital) towards this same symmetry compared to the corresponding
      achiral C(3v) species.

PMID- 20683536
TI  - Monitoring North Sea oil production discharges using passive sampling devices
      coupled with in vitro bioassay techniques.
AB  - Semipermeable membrane devices (SPMDs) and polar organic integrative chemical
      samplers (POCIS) were deployed in vicinity of an offshore oil production platform
      discharging production water (produced water) to the North Sea. Extracts from
      SPMDs and POCIS were subjected to chemical analysis for polycyclic aromatic
      hydrocarbons (PAHs) and alkylphenols (APs) respectively, and also assessed for
      acute toxicity (cytotoxicity), estrogen receptor (ER)-mediated production of
      vitellogenin (Vtg) and induction of 7-ethoxyresorufin-O-deethylase (EROD)
      activity in primary hepatocytes from rainbow trout (Oncorhynchus mykiss).
      Chemical analysis of the extracts revealed a gradient of exposure away from the
      platform for low molecular weight PAH and AP, whereas no exposure gradient was
      apparent for high molecular weight PAH, as expected. These data coupled with
      earlier work allowed a tentative general exposure scenario to be determined. The
      passive sampler extracts also caused modulation of the bioassay toxicity
      endpoints, although a clear gradient of response relative to the discharge point
      could not be identified.

PMID- 20683537
TI  - Unsymmetrical dizinc complexes as models for the active sites of
      phosphohydrolases.
AB  - The unsymmetrical dinucleating ligand 2-(N-isopropyl-N-((2
      pyridyl)methyl)aminomethyl)-6-(N-(carboxylmethyl)-N-((2
      pyridyl)methyl)aminomethyl)-4-methylphenol (IPCPMP or L) has been synthesized to
      model the active site environment of dinuclear metallohydrolases. It has been
      isolated as the hexafluorophosphate salt H(4)IPCPMP(PF(6))(2) x 2 H(2)O (H(4)L),
      which has been structurally characterized, and has been used to form two
      different Zn(II) complexes, [{Zn(2)(IPCPMP)(OAc)}(2)][PF(6)](2) (2) and
      [{Zn(2)(IPCPMP)(Piv)}(2)][PF(6)](2) (3) (OAc = acetate; Piv = pivalate). The
      crystal structures of and show that they consist of tetranuclear complexes with
      very similar structures. Infrared spectroscopy and mass spectrometry indicate
      that the tetranuclear complexes dissociate into dinuclear complexes in solution.
      Potentiometric studies of the Zn(II):IPCPMP system in aqueous solution reveal
      that a mononuclear complex is surprisingly stable at low pH, even at a 2:1
      Zn(II):L ratio, but a dinuclear complex dominates at high pH and transforms into
      a dihydroxido complex by a cooperative deprotonation of two, probably terminally
      coordinated, water molecules. A kinetic investigation indicates that one of these
      hydroxides is the active nucleophile in the hydrolysis of bis(2,4
      dinitrophenyl)phosphate (BDNPP) enhanced by complex 2, and mechanistic proposals
      are presented for this reaction as well as the previously reported
      transesterification of 2-hydroxypropyl p-nitrophenyl phosphate (HPNP) promoted by
      Zn(II) complexes of IPCPMP.

PMID- 20683538
TI  - Intramolecular cycloaddition in 6,6-spiroepoxycyclohexa-2,4-dienone: simple
      aromatics to (+/-)-platencin.
AB  - A formal total synthesis of platencin from a simple aromatic precursor is
      described. Transformation of the aromatic compound into reactive
      spiroepoxycyclohexa-2,4-dienone and intramolecular cycloaddition are the key
      features of our methodology. 2-Hydroxymethyl-6-(3-hydroxy-hex-5-enyl)-phenol was
      oxidized with NaIO(4) to give a dimer that, upon a retro-Diels-Alder reaction,
      generated the spiroepoxycyclohexa-2,4-dienone that underwent intramolecular Diels
      Alder reaction to give a tricyclic adduct having a core structure of platencin
      and appropriately disposed functional groups in a single step. Reduction of the
      double bond present in the ethano-bridge, manipulation of the oxirane ring and
      introduction of a double bond in the six-membered ring furnished a tricyclic
      intermediate which has already been converted into platencin.

PMID- 20683539
TI  - Microwave-assisted regioselective ring opening of non-activated aziridines by
      lithium aluminium hydride.
AB  - A new synthetic protocol for the LiAlH(4)-promoted reduction of non-activated
      aziridines under microwave conditions was developed. Thus, ring opening of 2
      (acetoxymethyl)aziridines provided the corresponding beta-amino alcohols, which
      were then used as eligible substrates in the synthesis of 5-methylmorpholin-2
      ones via condensation with glyoxal in THF. The same procedure was applied for the
      preparation of novel 5(R)- and 5(S)-methylmorpholin-2-ones starting from the
      corresponding enantiopure 2-(hydroxymethyl)aziridines. Additionally, 2
      (methoxymethyl)- and 2-(phenoxymethyl)aziridines were treated with LiAlH(4) under
      microwave irradiation, giving rise to either isopropylamines or 1-methoxypropan-2
      amines depending on the reaction conditions.

PMID- 20683540
TI  - Conjugation effect of the bridging ligand on the CO2 reduction properties in
      difunctional photocatalysts.
AB  - The photocatalytic activity for CO(2) reduction and optical and electrochemical
      properties of two Ru(II)-Re(I) binuclear complexes [Ru(dmb)(2)LRe(CO)(3)Cl](2+)
      (Ru-Re and Ru=Re, dmb = 4,4'-dimethyl-2,2'-bipyridine) with 1,2-bis(4'-methyl
      2,2'-bipyridyl-4-yl)ethane and 1,2-bis(4'-methyl-2,2'-bipyridyl-4-yl)ethene as
      bridging ligands have been investigated. The conjugation content of the bridging
      ligands plays an important role in the photocatalytic behavior: a saturated
      linkage exhibited more efficient than the conjugated.

PMID- 20683541
TI  - Ink-jetable patterning of metal-catalysts for regioselective growth of nanowires.
AB  - Nanosized (20-30 nm) colloidal gold, silver and their alloys were obtained by
      reductive transformation of corresponding metal salts. Dispersions of metal
      nanoparticles (sigma < 4%) in aqueous solutions were obtained by appropriate
      surface functionalization which led to inorganic inks with solid fraction ranging
      from 0.01-4%. Judicious choice of a polymer additive (polyethylene glycol or
      carboxymethyl cellulose) was found to be crucial to avoid the agglomeration of
      nanocrystals in the ink-jetted structures upon solvent evaporation. The
      versatility of the nanoparticle-based printing technology was demonstrated by
      fabrication of dot-matrices and circuitry patterns on different substrates.
      Characterization of printed structures showed a homogeneous topography (AFM) and
      uniform distribution of metallic nanoparticles (SEM/TEM) within the ink-jetted
      microdrops. The site-specific patterning on silicon (001) substrates with
      nanoparticle (mono)layers could also be achieved by printing the linker molecule,
      aminopropyltriethoxysilane, followed by selective attachment of gold
      nanoparticles. Positionally ordered and chemically bonded gold catalyst patterns
      were used for the chemical vapour deposition (CVD) of nanowires, which led to
      site-specific growth of nanowires via the vapour-liquid-solid (VLS) mechanism and
      unlike in the case of spin-coated metal colloids no significant lateral diffusion
      of metal nanoparticles was observed, in chemically anchored Au nanoparticles.
      Nanoparticle containing inks allow a user-defined dilution to vary the density of
      CVD grown nanowires, which was utilized to show the differences in catalytic
      activities of silver and gold catalysts in the VLS growth.

PMID- 20683542
TI  - Towards the total synthesis of calyculin C: preparation of the C(9)-C(25)
      spiroketal-dipropionate unit.
AB  - An asymmetric synthesis of the C(9)-C(25) spiroketal fragment of calyculin C is
      described. Key steps include two crotylation reactions using successively Brown's
      reagent and (Z)-crotyltrifluorosilane for the formation of the anti, anti, anti
      stereotetrad, ynone formation by a Pd-catalyzed coupling of a thiol ester with a
      terminal alkyne and a double intramolecular hetero-Michael addition for the
      stereoselective construction of the spiroketal framework.

PMID- 20683543
TI  - Cobalt complexes as the building blocks: {Co3+-Zn2+} heterobimetallic networks
      and their properties.
AB  - Two {Co(3+)-Zn(2+)} heterobimetallic coordination networks have been synthesized
      utilizing Co(3+) complex as the building blocks. The structural studies reveal 2D
      sheet-like networks where the Co(3+) containing building blocks are connected
      through Zn(2+) ions. Two different building blocks generate two unique networks
      as evidenced by the crystallographic studies and other properties. These networks
      are shown to catalyze Lewis metal ion assisted Strecker reaction in heterogeneous
      manner.

PMID- 20683544
TI  - Performance of the photo-Fenton process in the degradation of a model azo dye
      mixture.
AB  - The degradation of a model mixture composed of Acid Yellow 36 (AY36) and Methyl
      Orange (MO) azo dyes was performed using the photo-Fenton process (PFP). The
      performance of this process conducted under artificial UV light (365 nm) was
      compared with the Fenton reaction. Some important operating parameters that
      affect the degradation of azo dyes, such as initial Fe(2+) and H(2)O(2)
      concentrations and the presence or absence of chloride ions, were investigated.
      Decolorisation of the dye mixture sample was achieved in 70 min with the photo
      Fenton reaction, while the complete mineralization evaluated by TOC abatement was
      completed in 180 min. These results provide important knowledge for the treatment
      of wastewater containing azo dye mixtures by Fenton and photo-Fenton oxidation
      processes.

PMID- 20683545
TI  - Vectorial photoinduced electron transfer in multicomponent film systems of poly(3
      hexylthiophene), porphyrin-fullerene dyad, and perylenetetracarboxidiimide.
AB  - Multistage electron transfer in a film system consisting of a hole-transporting
      layer (HTL), donor-acceptor pair (D-A), and an electron-transporting layer (ETL)
      was studied by photovoltage and flash-photolysis techniques. Poly(3
      hexylthiophene) (PHT) was used as the HTL, while a symmetric porphyrin-fullerene
      dyad (P-F) and perylenetetracarboxidiimide (PTCDI) layers were functioning as the
      D-A pair and ETL, respectively. The photoexcitation of this three-component film
      system causes charge separations in the monomolecular P-F film, followed by
      electron transfer from the PHT polymer film and the fullerene anions to the
      porphyrin cations and the PTCDI layer, respectively. The final transient state is
      a charged PHT(+)|P-F|PTCDI(-) system, with significantly increased amplitude and
      lifetime of the photoelectrical signals compared to previously studied P-F|PTCDI
      and PHT|P-F systems, due to the its increased charge-separation distance. The
      study promotes the knowledge on the charge transfer mechanism in multilayered
      film systems.

PMID- 20683546
TI  - Splenic sclerosing haemangioma causes false-positive finding at FDG-PET.

PMID- 20683547
TI  - [E-learning in medicine with nuclear medicine as an example].

PMID- 20683548
TI  - Endoplasmic reticulum stress in age-related macular degeneration: trigger for
      neovascularization.
AB  - Age-related macular degeneration (AMD) can be classified into two main
      categories: the atrophic, dry form and the exudative, wet form. The crucial
      difference between dry and wet AMD is the development of choroidal
      neovascularization in wet AMD. One fundamental cause of the neovascularization is
      the increased expression of VEGF (vascular endothelial growth factor) in retinal
      pigment epithelial cells. Progression of AMD is linked to augmentation of
      cellular stress, for example, oxidative stress, proteotoxic stress, inflammation
      and hypoxia. All these conditions can trigger stress in endoplasmic reticulum
      (ER), which maintains protein quality control in cells. ER stress induces the
      unfolded protein response (UPR) via IRE1 (inositol-requiring protein-1), PERK
      (protein kinase RNA-like ER kinase) and ATF6 (activating transcription factor-6)
      transducers. UPR signaling is a double-edged sword, that is, it can restore
      cellular homeostasis as far as possible, but ultimately may lead to chronic,
      overwhelming stress that can cause apoptotic cell death. Interestingly, ER stress
      is a well-known inducer of angiogenesis in cancer. Moreover, stress conditions
      associated with the progress of AMD can induce the expression of VEGF. We discuss
      the role of ER stress in the regulation of neovascularization and the conversion
      of dry AMD to its wet, detrimental counterpart.

PMID- 20683549
TI  - Interleukin-1beta and interleukin-6 in arthritis animal models: roles in the
      early phase of transition from acute to chronic inflammation and relevance for
      human rheumatoid arthritis.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is the major target of the therapeutic
      approach in rheumatoid arthritis. A key issue in the approach to chronic
      arthritis is the understanding of the crucial molecules driving the transition
      from the acute phase to the chronic irreversible phase of the disease. In this
      review we analyzed five experimental arthritis animal models (antigen-induced
      arthritis, adjuvant-induced arthritis, streptococcal cell wall arthritis,
      collagen-induced arthritis and SKG) considered as possible scenarios to
      facilitate interpretation of the biology of human rheumatoid arthritis. The SKG
      model is strictly dependent on interleukin (IL)-6. In the other models, IL-1beta
      and IL-6, more than TNF-alpha, appear to be relevant in driving the transition,
      which suggests that these should be the targets of an early intervention to stop
      the course toward the chronic form of the disease.

PMID- 20683550
TI  - [Spatial analysis of the health risks associated with solid waste incineration: a
      preliminary analysis].
AB  - OBJECTIVES: to examine if emissions from the Vergueiro solid waste incinerator
      are associated with an increased risk of cancer in the population in its
      vicinity. METHODS: the area under influence of this incinerator was delimited by
      a 7 km radius from its geocoded centroid. Deaths of city residents in
      administrative districts inside this area due to cancer of lung, liver, larynx,
      non-Hodgkin's lymphoma in adults, leukemia, and all sites combined in children,
      in the 1998 to 2002 period, were selected and geocoded. The studied area was
      divided into 7 concentric rings delimited by a radius of 1 to 7 km from the
      incinerator. The analysis of the relationship between residential proximity to
      the incinerator and mortality due to cancer was based on the comparison of
      observed and expected cases, using the Stone test for decline in risk with
      distance from the incinerator. RESULTS: the area studied comprised 1,599,532
      inhabitants, of which 92,894 were children less than 5 years old and 634,993 were
      adults over 40 years old. No spatial gradient in risk was observed for any
      outcome in relation to distance from the incinerator. CONCLUSION: although no
      excess risk for the selected cancers were observed, emissions of incinerators
      still operating and their possible health effects should be monitored. The study
      of the spatial distribution of health events in areas around point sources of air
      pollution can become a methodological option for surveillance activities.

PMID- 20683551
TI  - Musculoskeletal disorders among workers in plastic manufacturing plants.
AB  - BACKGROUND: Epidemiological studies have indicated an association between
      musculoskeletal disorders (MSDs) and physical work demands. Psychosocial work
      demands have also been identified as possible risk factors, but findings have
      been inconsistent. OBJECTIVES: To evaluate factors associated with upper back,
      neck and upper limb MSD among workers from 14 plastic manufacturing companies
      located in the city of Salvador, Brazil. METHODS: A cross-sectional study design
      was used to survey a stratified proportional random sample of 577 workers. Data
      were collected by questionnaire interviews. Factor analysis was carried out on 11
      physical demands variables. Psychosocial work demands were measured by demand,
      control and social support questions. The role of socio-demographic factors,
      lifestyle and household tasks was also examined. Multiple logistic regression was
      used to identify factors related to upper back, neck and upper limb MSDs.
      RESULTS: Results from multiple logistic regression showed that distal upper limb
      MSDs were related to manual handling, work repetitiveness, psychosocial demands,
      job dissatisfaction, and gender. Neck, shoulder or upper back MSDs were related
      to manual handling, work repetitiveness, psychosocial demands, job
      dissatisfaction, and physical unfitness. CONCLUSIONS: Reducing the prevalence of
      musculoskeletal disorders requires: improving the work environment, reducing
      biomechanical risk factors, and replanning work organization. Programs must also
      be aware of gender specificities related to MSDs.

PMID- 20683552
TI  - Hospital morbidity among Guarani Indians in Southeastern and Southern Brazil.
AB  - Studies on hospital morbidity among Brazilian indigenous peoples are relatively
      recent, show limited coverage, and lack data sources capable of generating
      specific indicators according to ethnic group. The current study describes
      hospital morbidity in the indigenous population living in 83 Guarani villages in
      Southern and Southeastern Brazil (N=6,483), based on primary data obtained from a
      hospital admissions surveillance system implemented in 2007-2008, specifically
      for a case-control study on acute respiratory infections (ARI) in Guarani
      children. During the study period there were 666 hospitalizations in a total of
      497 individuals, the majority under 5 years of age (71.9%). Respiratory illnesses
      were the main causes of hospitalization (64.6%), especially in children (<5
      years: 77.6%; <1 year: 83.4%) and exceeded the proportions of hospital admissions
      from these causes in other indigenous groups. The overall hospitalization rate
      (per 100 person-years) was 8.8, or 71.4 under 1 year and 21.0 from 1 to 4 years
      of age. The ARI hospitalization rate (5.3) was 6.5 and 2.0 times higher than for
      diarrhea and other causes, respectively, while in children under 5 years of age
      (ARI=23.7) these differences were 7.4 and 5.4 times, respectively. The
      standardized Guarani hospitalization rate exceeded the standardized rates for the
      South and Southeast of Brazil by 40% and 210%, respectively. Hospitalization for
      primary care sensitive conditions and the high ARI rates indicate the need for
      studies to understand the epidemiology of ARI and investments to upgrade primary
      health care for the Guarani.

PMID- 20683553
TI  - Self-reported morbidity and its conditionings in children 5 to 9 years old in
      Sobral, CE, Brazil.
AB  - INTRODUCTION: This study was based on a random sample of 3,276 children aged
      between 5 and 9 years from the urban region of Sobral - CE, Brazil. OBJECTIVE:
      The main goal was to describe reported morbidity in children aged between 5 to 9
      years and to analyze their conditionings. METHODOLOGY: Home interviews were
      carried out with 3,276 children and clinical exams were conducted in a sub-sample
      of 2,594. Health problems reported by mothers were classified according to the
      tenth revision of the International Disease Classification. Analyses were
      performed using Stata 7.0. Outcomes analyzed were reported morbidity in the past
      15 days. The independent variables were grouped into socioeconomic,
      environmental, health service access, and nutritional status. RESULTS: The most
      prevalent morbidities were diseases of the respiratory system (DRS), 28.7%;
      diseases of the skin and subcutaneous tissue, 3.4%; infectious and parasitic
      diseases, 2.2%. The independent variables that had statistically significant
      correlations with the prevalence of DRS were related to the children who lived in
      the main urban center, had a history of malnutrition, and low school attendance,
      with odds ratio of respectively, 1.48 (1.10-1.9995%CI), 1.30 (1.05-1.6095%CI),
      1.54 (1.02-2.3295%CI). DISCUSSION: A high prevalence of DRS was observed in
      children in the main urban center. DRS prevalence was about twice higher than
      that observed in other studies with similar methodology. This observation has
      raised the hypotheses of over reporting or environmental pollution. Most children
      had minor health problems. They also had facilitated access to health services,
      especially to the FHP.

PMID- 20683554
TI  - Prevalence of asthma in schoolchildren in Alta Floresta- a municipality in the
      southeast of the Brazilian Amazon.
AB  - OBJECTIVE: To analyze the prevalence and symptoms of asthma in students of the
      Brazilian Amazon municipality of Alta Floresta-MT. METHODS: Cross-sectional study
      on the prevalence of asthma in 6 and 7 year-old children and 13 to 14 year-old
      adolescents, using the Study of Asthma and Allergies in Childhood - ISAAC method,
      phase I in 2007. Students who answered affirmatively question 2 - "presence of
      wheezing in the past 12 months" were considered asthmatic. RESULTS: Of the total
      2,071 students, 1,072 (51.7%) were children and 999 (48.3%) were teenagers. The
      prevalence of asthma was 21.4% among schoolchildren, and 12.4% among adolescents
      (chi2 = 29.29; rho = 0.00). Children presented a higher prevalence than
      adolescents of the following asthma symptoms: wheezing sometime in life (49.9%),
      wheezing in the past 12 months (21.4%), 1 to 3 wheezing attacks in the past 12
      months (16.4%), and dry cough at night (38.2%). Regarding physician-diagnosed
      asthma, no difference was observed between the two age groups, with a prevalence
      of around 6.0%. Male schoolchildren presented a higher prevalence of asthma,
      physician-diagnosed asthma and four or more wheezing episodes in the past 12
      months (rho < 0.05). Male adolescents presented the highest prevalence of strong
      wheezing affecting speech (rho < 0.05). CONCLUSION: Alta Floresta presents one of
      the highest prevalences of asthma in Latin America among schoolchildren in the 6
      and 7 year-old age group.

PMID- 20683555
TI  - [Agreement of anthropometric measures in a population-based epidemiological
      study: Ribeirao Preto, SP, 2006. OBEDIARP project].
AB  - This study aimed to assess the agreement between measured and self-reported
      height and weight measures in 632 adults. The agreement was calculated using an
      intra-class correlation coefficient (estimated by ANOVA using one classification
      criterion), mean differences and agreement limits, according to Bland and Altman.
      The intra-category agreement of the nutritional status was assessed by Kappa
      statistics. In men, ICCs were 0.926 (95%CI: 0.894-0.959) and 0.873 (95%CI: 0.799
      0.946), for weight and height measures, respectively, with the following mean
      difference and agreement limits for BMI: 0.143 kg/m(2) (-2.844-3.129). In women,
      ICCs were 0.981 (95%CI: 0.973-0.988) and 0.794 (95%CI: 0.687-0.900) respectively,
      with the following mean difference and agreement limits for BMI: 0.462 kg/m(2) (
      2.457-3.382). Kappa coefficients for nutritional status in men and women were,
      respectively, 0.777 (95%CI: 0.683-0.872) and 0.793 (95%CI: 0.725-0.862). Self
      reported measures are appropriate alternatives to classify nutritional status in
      epidemiological studies.

PMID- 20683556
TI  - [Reliability of anthropometric data obtained in children seen at the Primary
      Public Healthcare Service Network in Alagoas, Brazil].
AB  - INTRODUCTION: Monitoring child growth is a very important tool not only to build
      useful indicators for the evaluation and planning of public policies, but also
      for appropriate care to child health. In order to accomplish that anthropometric
      data from services need to present satisfactory reliability. OBJECTIVE: To
      investigate the reliability of weight and height variables obtained from children
      at public healthcare services (PHS) of Alagoas. METHODS: To build the sample, 20
      municipalities were drawn among the 102 of the state. Then, two PHS were drawn
      per municipality, and in these, about ten children under five years. The final
      sample consisted of 40 PHS and 347 children. Anthropometric measures (weight and
      height) were taken (1) during routine service (S); (2) by the researcher using
      standard equipment (R), and (3) by the researcher using service equipment (RS).
      RESULTS: The Kappa test indicated a "substantial" level of agreement (K=0.69) in
      the classifications of weight-for-age (WA) between S and R and "almost perfect"
      (K = 0.83) in those between RS and R. Regarding height-for-age (HA), the level of
      agreement between S and R was "fair" (K = 0.27), to "moderate" (K = 0.56) between
      RS and R. A Technical Measurement Error according to age groups (< or > 24
      months) indicated problems in the technique and equipment. Measurements of body
      weight obtained in PHS routine were systematically overestimated (p<0.05; sign
      test), leading to low sensitivity, high specificity and a high rate of false
      negatives (38.5% for WA and 57.1% for HA). CONCLUSION: The low reliability
      observed for the height variable cautions against its utilization to build health
      indicators, until the scenario can be improved. The weight variable may be used,
      but its quality must be improved by training anthropometrists, and through the
      acquisition and maintenance of equipment.

PMID- 20683557
TI  - [Food consumption of children and adolescents living in an area of invasion in
      Maceio, Alagoas, Brazil].
AB  - OBJECTIVE: To assess the food intake of energy, macronutrients and micronutrients
      related to growth and development in individuals under 16 years of age living in
      a consolidated invasion settlement in Maceio, Alagoas. METHODS: The assessment of
      food intake was carried out by the 24-hour recall method, using a food picture
      album. Nutritional composition of diets was analysed using the Virtual Nutri-1.0
      software. The estimated prevalence of inadequate intake was based on the Dietary
      Reference (DRIs), adjusted to account for intra-individual variability. The
      Statistical Package for Social Science (SPSS) version 11.5 was used for data
      analysis. RESULTS: 5.6% of the subjects studied presented excessive energy intake
      and for 3.7% it was inadequate. The frequency of excessive energy intake was
      higher in the 1 to 3 year-old age group (p <0.05), which also showed higher rates
      of inadequate intake of vitamin A, vitamin E and zinc, and it was the only group
      in which average consumption of calcium was higher than the adequate intake.
      CONCLUSION: Data show that dietary patterns of the individuals studied need
      adjustments.

PMID- 20683558
TI  - [Prevalence of barriers for physical activity in adolescents].
AB  - The aim of this study was to analyze the prevalence and association of barriers
      to physical activity among adolescents. This cross-sectional study evaluated a
      representative sample of public high school students in Curitiba-PR, Brazil. A
      total of 1,609 school adolescents (59.7% male) between 14 and 18 years of age
      answered a questionnaire on physical activity status and barriers to physical
      activity. Logistic regressions were conducted for each barrier investigated to
      verify the association between the prevalence of barriers and physical activity,
      adjusting for confounding variables (age and socioeconomic status). Analyses were
      done separately for boys and girls. Only 22% of boys and 9% of girls achieved the
      current physical activity recommendation. Among the 12 barriers investigated,
      only "there is nobody to take" did not differ between boys and girls. The
      perception of barriers was higher for girls than boys (p < 0.05) for all other
      barriers. "Lack of friends company" and "feel lazy" were the barriers most often
      reported by boys (30.4%) and girls (51.8%) respectively; however, the barrier
      most strongly associated with prevalence of physical inactivity was "prefer to do
      other things" for both boys (OR = 5.02 (2.69 - 9.37); p < 0.05) and girls (OR =
      7.10 (3.71 - 13.60); p < 0.05). Perceived barriers for the practice of physical
      activity were more prevalent in girls and differed as to the extent of importance
      between genders.

PMID- 20683559
TI  - [Physical activity and sedentary behavior among adolescent high school students].
AB  - OBJECTIVE: To identify the prevalence of factors associated with insufficient
      physical activity levels and sedentary behavior among adolescents. METHODS: In
      this cross-sectional study 4,210 students (14-19 years old) attending public high
      schools were selected using random two-stage cluster sampling. Data were
      collected by using the Global School-based Student Health Survey. Subjects who
      reported performing 60 minutes or more of moderate to vigorous physical activity
      five days a week or more were classified as physically active, while the
      remainder was classified as insufficiently active. Subjects who reported watching
      TV three or more hours a day were considered to be exposed to sedentary behavior.
      Analyses were carried out by using Chi-square tests and binary logistic
      regression. RESULTS: The prevalence of insufficiently active subjects was 65.1%
      (CI95% 63.7-66.6). Gender, place of residence (rural/urban), time of day
      attending school, occupational status, and enrollment in physical education were
      identified as factors significantly associated with exposure to insufficient
      levels of physical activity. Prevalence of exposure to sedentary behavior was
      40.9% (CI95% 39.4-42.4) on week days and 49.9% (CI95% 48.4-51.4) on weekend days.
      Place of residence, time of day attending school, occupational status and
      enrollment in physical education were identified as factors significantly
      associated with exposure to sedentary behavior on week days, whereas on weekend
      days exposure to sedentary behavior was related to gender, age and time of day
      attending school. CONCLUSION: This study showed a high prevalence of insufficient
      physical activity levels and exposure to sedentary behaviors among adolescents.

PMID- 20683560
TI  - Periodontitis in individuals with diabetes treated in the public health system of
      Belo Horizonte, Brazil.
AB  - OBJECTIVE: The aim of the present study was to investigate the prevalence of
      periodontitis among individuals with diabetes who use the public health system in
      the city of Belo Horizonte-Minas Gerais, Brazil, and the association of this
      condition with socioeconomic, behavioral and clinical variables. METHODS: A cross
      sectional study was carried out on a calculated sample of 300 individuals with
      diabetes. Periodontitis was defined as clinical attachment loss (CAL) > 3 mm in
      two or more non-adjacent teeth or those that exhibited CAL > 5 mm in 30.0% of
      teeth. All subjects were over 30 years of age and underwent a periodontal
      examination. Socioeconomic and behavioral characteristics as well as medical
      history and dental history were obtained from a structured interview.
      Multivariate analysis was conducted using Poisson regression. RESULTS: Among the
      individuals with diabetes, 6.7% exhibited good periodontal health, 68.0%
      exhibited gingivitis and 25.3% exhibited periodontitis. The following variables
      were associated with periodontitis after adjustment: male (PR 1.67 95% CI 1.12,
      2.49), individuals with diabetes for more than eight years (PR 1.63 95% CI 1.63,
      2.38), smokers (PR 1.71 95% CI 1.10, 2.65); individuals with more than 12 missing
      teeth (PR 2.67 95% CI 1.73, 4.15) CONCLUSIONS: Multiple determinants are
      associated with the prevalence of periodontitis among patients with diabetes.

PMID- 20683561
TI  - [Primary dental care indicators: association with socioeconomic status, dental
      care, water fluoridation and Family Health Program in Southern Brazil].
AB  - This paper analyzed the primary dental care indicators of the Brazilian National
      Health System (SUS) considering coverage of dental care, ratio between dental
      extraction and dental procedures, and coverage of preventive measures among
      children up to 14 years-old in the municipalities from the southern region of
      Brazil (n=1,159) between the years 2000 and 2005. In addition, the association of
      these indicators with socioeconomic indicators, dental care, water fluoridation
      and coverage of oral health care by the Family Health Program (FHP) was tested.
      The increase in the coverage of dental care was positively associated with the
      percentage of rural population, Human Development Index (HDI), number of dentists
      per capita, and FHP coverage. Dental extraction was negatively associated with
      percentage of rural population, HDI, number of dentists per capita, and FHP
      coverage, and positively associated with the Gini index. Preventive dental care
      measures were negatively associated with the Gini index, poverty and number of
      dentists per capita, and positively associated with the percentage of rural
      population, HDI, and FHP coverage.

PMID- 20683562
TI  - Fluoride varnishes and decrease in caries incidence in preschool children: a
      systematic review.
AB  - The objective of this systematic review was to evaluate whether there is
      conclusive evidence that the professional application of fluoride varnish
      decreases the incidence of dental caries in preschool children. We searched the
      BBO, LILACS, MEDLINE and Cochrane electronic databases to identify controlled
      clinical trials that evaluated the development of cavitated caries lesions in
      children up to six years of age. Two researchers performed a critical appraisal
      of the studies selected for inclusion. Five-hundred and thirteen articles were
      found, but only eight met our inclusion criteria. Most of these eight studies
      were of poor methodological quality. They were also heterogeneous in relation to
      participants' previous caries experience, type of intervention performed on the
      control group, children's exposure to other sources of fluoride, and varnish
      application interval. The absolute differences between caries incidences in the
      control and test groups ranged from 0.30 to 1.64 and the preventive fractions
      varied from 5% to 63%. Fluoride varnish may be effective to decrease the
      incidence of dental caries in preschoolers, but more randomized clinical trials
      with better methodological quality are necessary to provide conclusive evidence
      in this respect.

PMID- 20683563
TI  - [Individual determinants of dental care utilization among low-income adult and
      elderly individuals].
AB  - The utilization of dental care services results from the interaction of
      biological determinants with sociocultural, family and community variables, as
      well as from some characteristics of health systems. The objective of this study
      was to assess the individual factors associated with the use of dental care
      services among low-income adult and elderly individuals living in the catchment
      area of the Family Health Strategy, in Ponta Grossa, PR. The sample included 246
      individuals, aged 35 years or over, who answered a questionnaire on socioeconomic
      conditions, perceived needs, and access to dental care services. Data analysis
      was performed according to a conceptual framework based on Andersen's Behavioral
      Model. Non-recent use of dental care services was considered as the dependent
      variable in the logistic regression analysis models. There were high prevalences
      of self-reported oral health diseases and teeth loss. About 40% of the adults and
      67% of the elderly had not made any dental visit in the past 3 years. Individuals
      without ownership of the family home, with inadequate oral hygiene habits and who
      wore complete dentures had higher odds of having gone to the dentist longer ago.
      The fact of having a regular source of dental care was identified as a protective
      factor in the analysis. The conceptual framework confirmed the presence of social
      and psychosocial inequalities in the use of dental services among low-income
      adult and elderly individuals.

PMID- 20683564
TI  - [Obesity in adolescence and its main determinants].
AB  - The objective of this paper was to discuss the main environmental factors
      determining overweight and obesity in adolescents, based on a critical review of
      the subject. The main national and international health databases,
      Medline/PubMed, Web of Science, SciELO, and Lilacs were searched including
      publications from 1975 to 2009. The following key-words and respective MeSH terms
      were used: "overweight", "obesity", "adolescence", "adolescents", "physical
      activity", "food intake". The findings showed that changes in dietary patterns in
      recent decades as the increased consumption of simple sugars, processed foods,
      and inadequate intake of fruits and vegetables have contributed directly to the
      weight gain in this population. In addition, the progressive reduction in
      physical activity associated with increased time spent with low-intensity
      activities like television viewing, playing computer and video games has
      contributed to the weight gain of adolescents. In conclusion, variables related
      to dietary pattern and physical activity should be prioritized interventions
      directed toward the prevention of obesity among adolescents.

PMID- 20683565
TI  - [Indications for parathyroidectomy in renal hyperparathyroidism: comments on the
      significance of new therapeutics].
AB  - New therapeutics for the treatment of chronic kidney disease and secondary
      hyperparathyroidism, such as calcium and aluminium-free phosphate binders,
      calcimimetic agents and active vitamin D metabolites may decrease the need for
      parathyroidectomy. The calcimimetic cinacalcet does not induce a longer lasting
      regression of renal hyperparathyroidism and autonomous growing of parathyroids
      and the therapeutic effect is limited to the period of treatment. The classical
      indications for surgery, hypercalcemia, vascular calcification, severe
      osteopathy, drug-resistant hyperphosphatemia and calciphylaxis are still valid if
      patients do not respond to medical therapy under the condition that adynamic bone
      disease is excluded. Individual operative risk factors and improvement of quality
      of life are important supplementary factors for the indication for
      parathyroidectomy.

PMID- 20683566
TI  - [Lack of donor organs as an argument for living donors?].
AB  - In Germany more than 12,000 patients are presently waiting for an organ donation.
      Living donation makes sense for the long waiting time for a kidney, but it is not
      a permanent solution for the lack of organ donations. In the future topics which
      should be discussed are intensified public relations, a better family care and
      the allocation of rights and duties at the German coordinating agency. For all
      the prospects of success after a living donation the high standards of quality
      and security, which are targeted by the German donor organization in recipient
      protection, responsible evaluation of the expanded donor criteria and
      immunosuppressive therapy are all in favor of post-mortem organ donation. For all
      the phenomenal chance of success the priority of the post-mortem organ donation
      is regulated by law. The living donation remains an individual decision of the
      donor and the personal situation of life.

PMID- 20683568
TI  - [Indications for examination in a patient with angina pectoris and a low to
      moderate probability of coronary heart disease. CT angiography of coronary
      arteries, cardiac MRI or both?].

PMID- 20683567
TI  - [Pruritus and urticaria].
AB  - Urticaria is a frequent dermatological skin disease characterized by the
      occurrence of transient pruritic wheals. The sensation of pruritus has been
      described to be stinging, tickling and burning in patients with chronic
      urticaria. Because of the unpredictable attacks of pruritus and swelling,
      urticaria strongly affects the quality of life in patients. In this review we
      focus on clinical characteristics, therapeutic options and new pathophysiological
      mechanisms including the novel T-cell cytokine IL-31 in pruritus of patients with
      chronic urticaria.

PMID- 20683569
TI  - [Life without robots : What is left for the urologist?].
AB  - The triumphal march of robots in urology seems to be unstoppable. In the
      meantime, a broadening of the scope for indications in urology can be observed:
      this applies to pyeloplasty and to a lesser degree also to partial nephrectomy
      and radical cystectomy. As yet no evidence has been provided that robot-assisted
      radical prostatectomy (RP) is superior to open surgery. Furthermore, data are
      available which suggest that the midterm functional results are possibly even
      worse than those achieved with open RP.

PMID- 20683570
TI  - [Continuing medical education in andrology : Continuing education between wish
      and reality].
AB  - Andrology as a research topic has been well established for a long time - but
      andrological medical care has developed only recently. Medical doctors and
      scientists founded the German Society of Andrology (DGA) 35 years ago with the
      intention of promoting this field of medicine. Andrological skills are well
      established in the educational programme for residents in urology.The new
      regulations established in 2003 for residents in urology and certified urologists
      offer the chance to subspecialise in andrology. This specialisation constitutes
      progress, as patients now have a much better opportunity for identifying the
      andrologist as a competent partner for problems with fertility, hypogonadism and
      erectile dysfunction. Andrology comprises more than infertility - it covers the
      whole field of reproductive health in a broader sense: hypogonadism including
      genetic disorders, ejaculation disorders, erectile dysfunction, family planning
      and late-onset hypogonadism are included in the subspecialisation. There are
      minimum prerequisites concerning knowledge and skills that have to be fulfilled
      by urologists, dermatologists or endocrinologists. Surgical andrological
      procedures are better established in European than in German educational
      programmes. The educational programme has to be performed within 18 months; 6 of
      these months can be completed during residency training in urology.The importance
      of andrologists particularly in the setting of reproductive medicine is more than
      obvious: the Federal Medical Council clearly defines that an andrologist has to
      be involved in fertility centres performing assisted reproduction. According to
      the data compiled by Jens Jacobeit, responsible member for medical training of
      the DGA, 929 andrologists had achieved their certification in Germany at the end
      of the year 2009. The qualifying andrological postgraduate training is a duty and
      at the same time a chance for the urological community to professionally cover
      this field of subspecialisation in the future.

PMID- 20683574
TI  - Transgenic expression of haem oxygenase-1 in pancreatic beta cells protects non
      obese mice used as a model of diabetes from autoimmune destruction and prolongs
      graft survival following islet transplantation.
AB  - AIMS/HYPOTHESIS: Haem oxygenase 1 (HO-1) has strong anti-apoptotic, anti
      inflammatory and antioxidative effects that help protect cells against various
      forms of immune attack. We investigated whether transgenic expression of Ho-1
      (also known as Hmox1) in pancreatic beta cells would protect NOD mice from
      autoimmune damage and prolong graft survival following islet transplantation.
      METHODS: To evaluate the protective effect of beta cell-specific HO-1 in
      autoimmune diabetes, we used an insulin promoter-driven murine Ho-1 construct
      (pIns-mHo-1) to generate a transgenic NOD mouse. Transgene expression, insulitis
      and the incidence of diabetes in mice were characterised. Lymphocyte composition,
      the development of T helper (Th)1, Th2 and T regulatory (Treg) cells, T cell
      proliferation and lymphocyte-mediated disease transfer were analysed. The
      potential effects of transgenic islets and islet transplantation on apoptosis,
      inflammation and the generation of reactive oxygen species (ROS) and reactive
      nitrogen species (RNS) were evaluated. RESULTS: Transgenic mice showed less
      severe insulitis and a lower incidence of diabetes than non-transgenic control
      littermates. Lymphocyte composition and functions were not affected. Islets from
      transgenic mice expressed lower levels of proinflammatory cytokines/chemokines,
      proapoptotic gene expression and amounts of ROS/RNS, and were more resistant to
      TNF-alpha- and IFN-gamma-induced apoptosis. Islet grafts from transgenic mice
      also survived longer in diabetic recipients than control islets.
      CONCLUSIONS/INTERPRETATION: Transgenic overexpression of Ho-1 in beta cells
      protected NOD mice from diabetes and delayed the autoimmune destruction of islet
      grafts, providing valuable insight into the development of better strategies for
      clinical islet transplantation in patients with type 1 diabetes.

PMID- 20683575
TI  - Late urethral erosion of transobturator suburethral mesh (Obtape): a minimally
      invasive management under local anaesthesia.
AB  - The placement of transobturator sub-urethral synthetic tapes, although with a
      high success rate of achieving continence, carries the risk of tape erosion to
      adjacent structures. While vaginal erosion occurs more frequently, urethral
      erosion has also been reported, usually in the immediate or early postoperative
      period. We present two different cases of urethral erosion with the Obtape sling,
      the first one diagnosed 1 year after surgery and the second one, a very late
      complication, occurring 4 years after the placement of the sling. Although
      transvaginal urethrotomy with tape resection has been the most popular approach
      described in the literature, we describe a minimally invasive trans-urethral
      approach for the management of this complication under local anaesthesia. We also
      present some "tricks of the trade" on retrieving the tape trans-urethrally while
      maximizing the length of tape removed.

PMID- 20683576
TI  - Risk factors associated with voiding dysfunction after anti-incontinence surgery.
AB  - INTRODUCTION AND HYPOTHESIS: The aim of this study is to investigate the risk
      factors of voiding dysfunction occurring within 1 month after surgical treatment
      of urinary incontinence. METHODS: Medical records of 903 women who underwent anti
      incontinence surgery at Yonsei Medical Health System from January 1999 to April
      2007 were reviewed. The patient demographics, urodynamic parameters, pelvic organ
      prolapse stage, surgical procedures, and concomitant surgery were retrospectively
      evaluated. Postoperative voiding dysfunction was defined as post-void residual
      urine measuring greater than 100 cc at two or more successive trials. RESULTS:
      Age, menopausal status, maximum flow rate, average flow rate, post-void residual,
      anti-incontinence surgery type, stage of pelvic organ prolapse, and concomitant
      prolapse surgery were associated predictors of voiding dysfunction after anti
      incontinence surgery. In multivariate analysis, concomitant anterior colporrhaphy
      (OR 2.4; 95% CI 1.38-4.11) was the only independent risk factor. CONCLUSIONS: The
      most important risk factor associated with voiding dysfunction was concomitant
      anterior colporrhaphy.

PMID- 20683578
TI  - Vaginal mesh grafts and the Food and Drug Administration.

PMID- 20683579
TI  - Total transvaginal mesh (TVM) technique for treatment of pelvic organ prolapse: a
      3-year prospective follow-up study.
AB  - INTRODUCTION AND HYPOTHESIS: To evaluate clinical outcomes at 3 years following
      total transvaginal mesh (TVM) technique to treat vaginal prolapse. METHODS:
      Prospective, observational study in patients with prolapse >= stage II. Success
      was defined as POP-Q-stage 0-I and absence of surgical re-intervention for
      prolapse. Secondary outcome measures were: quality of life (QOL), prolapse
      specific inventory (PSI), impact on sexual activity and complications. RESULTS:
      Ninety women underwent TVM repair, 72 a hysterectomy. Anatomical failure rate was
      20.0% at 3 years. Three patients required re-intervention for prolapse.
      Improvements in QOL- and PSI-scores were observed at 1 and 3 years. Vaginal mesh
      extrusion occurred in 14.4% patients. After 3 years, 4.7% asymptomatic extrusions
      remained present. Of 61 sexually active women at baseline, a significant number
      of patients (41%) ceased sexual activity by 3 years; de novo dyspareunia was
      reported by 8.8%. One vesico-vaginal fistula resolved after surgery. CONCLUSION:
      Medium-term results demonstrate that the TVM technique provides a durable
      prolapse repair.

PMID- 20683580
TI  - Postoperative infections due to bladder catheters after anterior colporrhaphy: a
      prospective, randomized three-arm study.
AB  - INTRODUCTION AND HYPOTHESIS: Different forms of urinary drainage are applied
      after anterior colporrhaphy. Suprapubic urinary catheter (SUC) and indwelling
      urinary catheter (IUC) for 2 to 96 h are preferred. If there is no difference in
      symptomatic urinary tract infection (SUTI) or complications between IUCs for 96
      and 24 h, the latter will be considered sufficient. If IUCs have no higher rate
      of infections or complications compared to SUC for 96 h, the former could be
      considered sufficient. METHODS: It was a three-arm prospective, randomized study
      including 257 patients. The three arms were: IUCs for 24 h, IUCs for 96 h, and
      SUCs for 96 h. RESULTS: We found no significant difference in SUTIs between all
      three groups. Although the SUC arm showed no SUTIs, a significant higher rate of
      complications was seen. CONCLUSION: The optimal bladder catheter after anterior
      colporrhaphy was, in our trial, the IUC for 24 h.

PMID- 20683581
TI  - Lutein improves antioxidant defense in vivo and protects against DNA damage and
      chromosome instability induced by cisplatin.
AB  - Lutein (LT) is the second most prevalent carotenoid in human serum, and it is
      abundantly present in dark, leafy green vegetables. The objectives of this study
      were to evaluate the genotoxicity and mutagenicity of LT, and its protective
      effects in vivo against DNA damage and chromosome instability induced by
      cisplatin (cDDP). For this purpose, we used the comet assay and micronucleus (MN)
      test, and we evaluated the antioxidant effects of LT by determination of
      enzymatic (catalase-CAT) and non-enzymatic (reduced glutathione-GSH) activity.
      Mice were divided into six groups: cDDP, mineral oil (OM), LT groups and LT +
      cDDP groups. To perform the MN test on peripheral blood (PB) cells, blood samples
      were collected before the first treatment (T0), and 36 h (T1) and 14 days (T2)
      after the first treatment. To perform the comet assay, blood samples were
      collected 4 h after the first and the last treatment. Oxidative capacity was
      analyzed in total blood that was collected 24 h after the last treatment, when
      bone marrow (BM) sample was also collected for the MN test. No genotoxic or
      mutagenic effects of LT were observed for the doses evaluated. We did find that
      this carotenoid was able to reduce the formation of crosslinks and chromosome
      instability induced by cDDP. No differences were observed in CAT levels, and LT
      treatment increased GSH levels compared with a negative control group,
      reinforcing the role of this carotenoid as an antioxidant.

PMID- 20683582
TI  - Ontogeny of the stimulant and sedative effects of ethanol in male and female
      Swiss mice: gradual changes from weaning to adulthood.
AB  - RATIONALE: The adolescent period is characterized by a specific sensitivity to
      the effects of alcohol, which is believed to contribute to the enhanced risks of
      alcohol dependence when drinking is initiated early during adolescence. In
      adolescent rodents, while the reduced sensitivity to the sedative effects of
      ethanol has been well characterized, its stimulant effects have not yet been
      extensively studied. OBJECTIVES: The present study characterized the development
      of the stimulant and the sedative effects of acute ethanol in male and female
      Swiss mice from weaning to early adulthood and tested whether both effects are
      interrelated. METHODS: In a first experiment, mice aged 21, 28, 35, 42, and 60
      days were injected with various ethanol doses and tested for ethanol-induced
      locomotor activity. In an independent experiment, mice of the same groups of age
      were injected with 4 g/kg ethanol and ethanol-induced sedation was quantified
      with the loss of righting reflex procedure. RESULTS: In male and female mice, the
      stimulant effects of ethanol gradually decreased, whereas its sedative effects
      increased with age. When the sedation was statistically controlled using a
      covariance analysis, the differences between adult and juvenile mice in the
      locomotor stimulation were significantly reduced. CONCLUSIONS: From weaning to
      early adulthood, the acute stimulant and sedative effects of ethanol show gradual
      changes that are similar in male and female mice. Although the initial tolerance
      to the sedative effects of ethanol contributes to the changes in ethanol-induced
      locomotor activity, young mice also show a higher sensitivity to the stimulant
      effects of ethanol.

PMID- 20683583
TI  - Lack of a rewarding effect and a locomotor-enhancing effect of the selective MU
      opioid receptor agonist amidino-TAPA.
AB  - RATIONALE AND OBJECTIVES: Psychological dependence is one of the worst side
      effects of morphine. It limits the clinical availability of morphine and non
      patient morphine users suffer from addiction. An analgesic, which is more potent
      than morphine but without the liability of psychological dependence, has long
      been sought in the clinic. We have recently developed a new MU-opioid receptor
      agonist, N(alpha)-amidino-Tyr-D-Arg-Phe-beta-Ala (amidino-TAPA), as a potent
      analgesic with an antinociceptive profile that is distinct from morphine,
      including the release of endogenous kappa-opioid peptides. The activation of
      kappa-opioid receptors has been suggested to suppress the development of
      psychological dependence by MU-opioid receptor agonists. In the present study,
      the psychological dependence liability and the related locomotor-enhancing effect
      of amidino-TAPA were evaluated. RESULTS: Amidino-TAPA injected subcutaneously
      produced an extremely potent and longer lasting antinociception than morphine in
      ddY mice, prodynorphin-knockout mice, and wild-type C57BL/6J mice. Unlike
      subcutaneously injected morphine, which had potent locomotor-enhancing and
      rewarding effects at antinociceptive doses in ddY mice, amidino-TAPA injected
      subcutaneously did not induce significant locomotor-enhancing and rewarding
      effects at antinociceptive or even higher doses in ddY mice. In wild-type
      C57BL/6J mice, amidino-TAPA showed the same pharmacological profile (potent
      antinociception, lack of locomotor-enhancing and rewarding effects) as in ddY
      mice. However, amidino-TAPA produced potent locomotor-enhancing and rewarding
      effects at antinociceptive doses in prodynorphin-knockout mice. CONCLUSIONS: The
      present results suggest that amidino-TAPA is a potent analgesic without the
      liability of psychological dependence because it releases endogenous kappa-opioid
      peptides.

PMID- 20683584
TI  - Quantitative estimation of riluzole in human plasma by LC-ESI-MS/MS and its
      application to a bioequivalence study.
AB  - A novel simple, sensitive, selective, and rapid high-performance liquid
      chromatography coupled with tandem mass spectrometry method was developed and
      validated for quantification of riluzole in human plasma. The chromatography was
      performed by using a Zorbax-SB-C18 (4.6 x 75 mm, 3.5 microm) column , isocratic
      mobile phase 0.1% formic acid/acetonitrile (10:90 v/v), and an isotope-labeled
      internal standard (IS), [(13)C,(15)N(2)]riluzole. The extraction of drug and
      internal standard was performed by liquid-liquid extraction and analyzed by MS in
      the multiple reaction monitoring (MRM) mode using the respective [M+H](+) ions,
      m/z 235.0/165.9 for riluzole and m/z 238.1/169.0 for the IS. The calibration
      curve was linear over the concentration range 0.5-500.0 ng/ml for riluzole in
      human plasma. The limit of quantification (LOQ) was demonstrated at 0.5 ng/ml.
      The within-batch and between-batch precision were 0.6-2.3% and 1.4-5.7%, and
      accuracy was 97.1-101.1% and 98.8-101.2% for riluzole respectively. Drug and IS
      were eluted within 3.0 min. The validated method was successfully applied in a
      bioequivalence study of riluzole in human plasma.

PMID- 20683585
TI  - A simple method of surface functionalisation for immuno-specific immobilisation
      of proteins.
AB  - We present a new and advanced methodology, developed for surface
      functionalisation of gold and to study immobilisation of an immuno-specific
      system of proteins. A combination of electrochemical quartz crystal microbalance
      and Raman spectroscopy techniques allowed a complete understanding of the system
      starting from surface functionalisation and progressing to the functional
      structure analysis of immobilised proteins. A simple electrochemical procedure
      was formulated to prepare sulphonyl chloride terminated gold surfaces that form a
      strong sulphonamide bond with the receptor protein staphylococcal protein A
      (SpA). On the SpA grafted surfaces, the immobilisation of a human IgG and
      consecutive binding of an immuno-specific anti-human IgG was observed. The
      surface functional groups form a strong interaction with SpA without disturbing
      its functional properties. The native functional structure of SpA and also the
      IgGs was found to be retained in their immobilised state.

PMID- 20683586
TI  - Recent advances in micro-scale and nano-scale high-performance liquid-phase
      chromatography for proteome research.
AB  - High-performance liquid chromatography-electrospray ionization tandem mass
      spectrometry (HPLC-ESI-MS-MS) is regarded as one of the most powerful techniques
      for separation and identification of proteins. Recently, much effort has been
      made to improve the separation capacity, detection sensitivity, and analysis
      throughput of micro- and nano-HPLC, by increasing column length, reducing column
      internal diameter, and using integrated techniques. Development of HPLC columns
      has also been rapid, as a result of the use of submicrometer packing materials
      and monolithic columns. All these innovations result in clearly improved
      performance of micro- and nano-HPLC for proteome research.

PMID- 20683587
TI  - Molecular characterization and geological microenvironment of a microbial
      community inhabiting weathered receding shale cliffs.
AB  - Shales play an important role in many earth system processes including coastal
      erosion, and they form the foundations of many engineering structures. The
      geobiology of the interior of pyrite-containing receding shale cliffs on the
      coast of northeast England was examined. The surface of the weathered shales was
      characterised by a thin layer of disordered authigenic iron oxyhydroxides and
      localised acicular, platy and aggregated gypsum, which was characterised by Raman
      spectroscopy, XAS and SEM. These chemical changes are likely to play an important
      role in causing rock weakening along fractures at the micron scale, which
      ultimately lead to coastal retreat at the larger scale. The surface of the shale
      hosts a novel, low-diversity microbial community. The bacterial community was
      dominated by Proteobacteria, with phylotypes closely associating with
      Methylocella and other members of the gamma-subdivision. The second largest
      phylogenetic group corresponded to Nitrospira. The archaeal 16S rRNA phylotypes
      were dominated by a single group of sequences that matched phylotypes reported
      from South African gold mines and possessed ammonia monooxygenase (amoA) genes.
      Both the phylogenetic and the mineral data show that acidic microenvironments
      play an important role in shale weathering, but the shale has a higher microbial
      diversity than previously described pyritic acid mine drainage sites. The
      presence of a potentially biogeochemically active microbial population on the
      rock surface suggests that microorganisms may contribute to early events of shale
      degradation and coastal erosion.

PMID- 20683588
TI  - Soil microbial abundance and diversity along a low precipitation gradient.
AB  - The exploration of spatial patterns of abundance and diversity patterns along
      precipitation gradients has focused for centuries on plants and animals;
      microbial profiles along such gradients are largely unknown. We studied the
      effects of soil pH, nutrient concentration, salinity, and water content on
      bacterial abundance and diversity in soils collected from Mediterranean, semi
      arid, and arid sites receiving approximately 400, 300, and 100 mm annual
      precipitation, respectively. Bacterial diversity was evaluated by terminal
      restriction fragment length polymorphism and clone library analyses and the
      patterns obtained varied with the climatic regions. Over 75% of the sequenced
      clones were unique to their environment, while ~2% were shared by all sites, yet,
      the Mediterranean and semi-arid sites had more common clones (~9%) than either
      had with the arid site (4.7% and 6%, respectively). The microbial abundance,
      estimated by phospholipid fatty acids and real-time quantitative PCR assays, was
      significantly lower in the arid region. Our results indicate that although soil
      bacterial abundance decreases with precipitation, bacterial diversity is
      independent of precipitation gradient. Furthermore, community composition was
      found to be unique to each ecosystem.

PMID- 20683589
TI  - Diversity and abundance of oil-degrading bacteria and alkane hydroxylase (alkB)
      genes in the subtropical seawater of Xiamen Island.
AB  - In this report, the diversity of oil-degrading bacteria and alkB gene was
      surveyed in the seawater around Xiamen Island. Forty-four isolates unique in 16S
      rRNA sequence were obtained after enrichment with crude oil. Most of the obtained
      isolates exhibited growth with diesel oil and crude oil. alkB genes were
      positively detected in 16 isolates by degenerate polymerase chain reaction (PCR).
      And for the first time, alkB genes were found in bacteria of Gallaecimonas,
      Castellaniella, Paracoccus, and Leucobacter. Additional 29 alkB sequences were
      retrieved from genomic DNA of the oil-degrading communities. Phylogenetic
      analysis showed that the obtained alkB genes formed five groups, most of which
      exhibited 60-80% similarity at the amino acid level with sequences retrieved from
      the GenBank database. Furthermore, the abundance of alkB genes in seawater was
      examined by real-time PCR. The results showed that alkB genes of each group in
      situ ranged from about 3 * 10(3) to 3 * 10(5) copies L(-1), with the homologs of
      Alcanivorax and Pseudomonas being the most predominant. Bacteria of Alcanivorax,
      Acinetobacter, and Pseudomonas are important oil degraders in this area; while
      those frequently reported in other area, like Oleiphilus spp., Oleispira spp.,
      and Thalassolituus spp. were not found in our report. These results indicate that
      bacteria and genes involved in oil degradation are quite diverse, and may have
      restriction in geographic distribution in some species.

PMID- 20683590
TI  - Development of a DNA microarray for detection of expressed equine classical MHC
      class I sequences in a defined population.
AB  - Development of an accurate and efficient molecular-based equine MHC class I
      typing method would facilitate the study of T lymphocyte immune responses in
      horses. Here, a DNA microarray was designed to detect expressed classical MHC
      class I genes comprising serologically defined equine leukocyte antigen (ELA)-A
      haplotypes represented in a closed Arabian horse breeding herd. Initially,
      cloning and sequencing of RT-PCR products were used to identify sequences
      associated with the ELA-A1, A4, and W11 haplotypes, and one undefined haplotype,
      in six horses. Subsequently, sequence-specific, conserved (positive control), and
      random nucleotide (negative control) 23- to 27-mer oligonucleotide microarray
      probes were designed and spotted onto an epoxy-coated masked slide using a
      robotic arrayer. Bulk RT-PCR products from each horse were biotinylated by nick
      translation, hybridized to the array, and detected using tyramide signal
      amplification. The microarray consistently detected eight of nine classical MHC
      class I transcripts and allowed ELA haplotypic associations to be made. Cloning
      and sequencing of RT-PCR products were then performed in a group of ELA disparate
      horses and ponies, in which six novel sequences were identified. This group was
      used to determine the specificity of the array. Overall, the microarray was more
      efficient than cloning and sequencing for detecting expressed classical MHC class
      I sequences in this defined population of horses, and was significantly more
      specific than serology. These results confirmed the utility of a microarray-based
      method for high-resolution MHC class I typing in the horse. With additional
      probes the array could be useful in a broader population.

PMID- 20683591
TI  - 99mTc-labelled macroaggregated albumin (MAA) scintigraphy for planning treatment
      with 90Y microspheres.
AB  - PURPOSE: 90Y microspheres are used for intra-arterial treatment of liver tumours.
      In the patient preparation, a hepatic angiogram is performed and all arteries
      that could transport microspheres from the targeted liver vasculature to
      extrahepatic organs are blocked. 99mTc-labelled macroaggregated albumin (MAA) is
      injected intra-arterially to simulate the treatment and whole-body scintigraphy
      and single photon emission computed tomography (SPECT) of the abdomen are
      performed. METHODS: Various aspects of lung shunt fraction (LSF) estimation were
      studied: interobserver and intrapatient variability, influence of scan quality
      and underlying disease. Secondly, the interobserver variability in reading the
      MAA SPECT of the abdomen was investigated. We reviewed 90 whole-body scans and 20
      SPECT scans performed at our institution. Readers were blinded to each other's
      findings. Scoring the scan quality was based on the visualization of tracer
      degradation. RESULTS: The mean difference in LSF between the readers was 1%. In 1
      of 23 patients who underwent repeated MAA injections a marked change in LSF was
      observed. No significant differences in LSF were recorded for primary versus
      secondary liver tumours. There was a correlation between scan quality and LSF,
      suggesting that low scan quality leads to overestimation of the LSF. Concordant
      results in ruling out the presence of extrahepatic tracer deposition were reached
      in 17 of 20 scans (85%). CONCLUSION: Interobserver and intrapatient variability
      in LSF calculation was limited. LSF was clearly dependent on scan quality. The
      underlying disease had no significant impact on the LSF. Interobserver
      variability for reading the MAA SPECT scans was acceptable.

PMID- 20683592
TI  - Administration of embryonic stem cells generates effective antitumor immunity in
      mice with minor and heavy tumor load.
AB  - The history of immunizing animals with fetal tissues to generate an antitumor
      response dates back a century ago. Subsequent reports supported the idea that
      vaccination with embryonic materials could generate cancer-specific immunity and
      protect animals from transplantable and chemically induced tumors. In our study,
      we found C57 BL/6 mice vaccinated with embryonic stem cells (ESCs) received
      obvious antitumor immunity, which protected them from the formation and
      development of lung cancer. Furthermore, we investigated the antitumor effects of
      administration of ESCs in mice with minor and/or heavy tumor load. The tumor
      growth was monitored, the proliferation of lymphocytes and secretion of cytokines
      were examined, and finally the tissue sections were approached by
      immunohistochemical and apoptosis staining. The results suggested that mice
      injected with ESCs received obvious tumor inhibition and retardation due to
      significant lymphocyte proliferation and cytokine secretion, which help to
      rebuild the host's immunity against cancer to some extent and comprise the main
      part of antitumor immunity. Moreover, mice with minor tumor load received
      stronger antitumor effect compared with mice with heavy tumor load, may be due to
      relatively intact immune system. Thus, besides their function as prophylactic
      vaccines, administration of ESCs could be a potential treatment for cancer, which
      obviously prevent and control the proliferation and development of malignant
      tumors.

PMID- 20683593
TI  - The role of reduction and internal fixation of Lisfranc fracture-dislocations: a
      systematic review of the literature.
AB  - A systematic review of the literature was performed in order to evaluate the role
      of reduction and internal fixation in the management of Lisfranc joint fracture
      dislocations. Articles were extracted from the Pubmed database and the retrieved
      reports were included in the study only if pre-specified eligibility criteria
      were fulfilled. Eleven articles were eligible for the final analysis, reporting
      data for the management of 257 patients. Injuries of the first three metatarsal
      rays were treated by closed reduction and internal fixation with screws in 16.3%
      of the patients, open reduction and internal fixation with screws in 66.5% and
      open reduction and internal fixation with Kirschner wires (K-wires) in 17.1% of
      the patients. The preferred method for the stabilisation of the fourth and fifth
      metatarsal rays was K-wires. Screw-related complications were common and were
      reported in 16.1% of the cases. The mean American Orthopaedic Foot and Ankle
      Society midfoot score was 78.1 points. Post-traumatic radiographic arthritis was
      reported in 49.6% of the patients, but only in 7.8% of them it was severe enough
      to warrant an arthrodesis. We conclude that open reduction and internal fixation
      of the first three metatarsal rays with screws is a reliable method for the
      management of Lisfranc injuries. This can be complemented by K-wires application
      in the fourth and fifth metatarsal rays if needed.

PMID- 20683594
TI  - Hemolysis in Wilson's disease.

PMID- 20683595
TI  - Procollagen type I N-propeptide is a predictor of skeletal morbidity in patients
      with malignant osteolytic bone disease on bisphosphonates.
AB  - BACKGROUND: There is an urgent need for individualized treatment of malignant
      bone disease (MBD), as the clinical benefit from bone-targeted therapies is
      moderate. We assessed the predictive value of the bone formation marker
      procollagen type I N-propeptide (PINP) for skeletal morbidity in patients with
      MBD receiving pamidronate. METHODS: Seventy patients with advanced MBD were
      randomized to receive pamidronate 60 mg (n = 35) or 90 mg (n = 35) every 3 weeks
      for six cycles in a double-blind study. PINP was analyzed at baseline and before
      each administration of pamidronate, using a validated ELISA. Serum PINP
      concentrations were compared with pain response (visual analog scale VAS,
      composite pain score) and skeletal morbidity (skeletal-related events, SRE) using
      Student's T-test, Wilcoxon rank-sum and log-rank test, respectively. RESULTS:
      Patients with >=20% pain reduction in the VAS had lower baseline PINP
      concentrations when compared to patients with <20% VAS response (P < 0.0001). A
      high baseline serum PINP concentration (highest tertile versus lower two
      tertiles) was significantly associated with a shorter duration of pain response
      (P < 0.0001) and a shorter time interval to first SRE (P < 0.008). Sensitivity of
      a low baseline PINP serum concentration for freedom from SRE at 1 year from
      randomization was 75% (15 out of 20 patients), while specificity was 82% (27 out
      of 33 patients). CONCLUSIONS: Serum PINP has been shown to be a significant
      predictor for skeletal morbidity in patients with MBD on pamidronate treatment.
      Prospective validation of PINP in patients with MBD to assess the prognosis or
      individualize bone-targeted treatment is justified.

PMID- 20683596
TI  - A combined pharmacokinetic model for the hypoxia-targeted prodrug PR-104A in
      humans, dogs, rats and mice predicts species differences in clearance and
      toxicity.
AB  - BACKGROUND: PR-104 is a phosphate ester that is systemically converted to the
      corresponding alcohol PR-104A. The latter is activated by nitroreduction in
      tumours to cytotoxic DNA cross-linking metabolites. Here, we report a population
      pharmacokinetic (PK) model for PR-104 and PR-104A in non-human species and in
      humans. METHODS: A compartmental model was used to fit plasma PR-104 and PR-104A
      concentration-time data after intravenous (i.v.) dosing of humans, Beagle dogs,
      Sprague-Dawley rats and CD-1 nude mice. Intraperitoneal (i.p.) PR-104 and i.v. PR
      104A dosing of mice was also investigated. Protein binding was measured in plasma
      from each species. Unbound drug clearances and volumes were scaled
      allometrically. RESULTS: A two-compartment model described the disposition of PR
      104 and PR-104A in all four species. PR-104 was cleared rapidly by first-order
      (mice, rats, dogs) or mixed-order (humans) metabolism to PR-104A in the central
      compartment. The estimated unbound human clearance of PR104A was 211 L/h/70 kg,
      with a steady state unbound volume of 105 L/70 kg. The size equivalent unbound PR
      104A clearance was 2.5 times faster in dogs, 0.78 times slower in rats and 0.63
      times slower in mice, which may reflect reported species differences in PR-104A O
      glucuronidation. CONCLUSIONS: The PK model demonstrates faster size equivalent
      clearance of PR-104A in dogs and humans than rodents. Dose-limiting myelotoxicity
      restricts the exposure of PR-104A in humans to approximately 25% of that
      achievable in mice.

PMID- 20683597
TI  - The diffusion-weighted imaging perfusion fraction f is a potential marker of
      sorafenib treatment in advanced hepatocellular carcinoma: a pilot study.
AB  - OBJECTIVE: To determine the total Apparent Diffusion Coefficient (ADC), the pure
      Diffusion coefficient (D) and the perfusion fraction (f) in advanced
      hepatocellular carcinoma (HCC) under sorafenib treatment. MATERIALS AND METHODS:
      Two target tumors were prospectively analyzed in 12 patients at baseline, 2-weeks
      and 2-months treatment using b values of 0, 200, 400, 800 s/mm. Repeatability
      error was estimated on a healthy volunteer. RESULTS: Lesion sizes, ADC and D
      values did not significantly change during treatment (overall mean values,
      respectively, 47.8 +/- 31.0 mm, 1.34 +/- 0.14 * 10-3 mm2 s and 1.18 +/- 0.22 * 10
      3 mm2/s). However, f values significantly increased in seven responder patients
      (+38.39% at 2-weeks, +50.94% at 2-months, P = 0.005) while they decreased in five
      non responder patients (-41.93% at 2-weeks, P = 0.006). Furthermore, f was
      inversely correlated with alphaFP levels (P = 0.032) and responder patients had a
      higher mean overall survival (OS) than non responder patients (12.29 +/- 4.46 vs.
      7.80 +/- 4.9 months). The % variation of f relative to baseline at 2-months was
      correlated with OS (P = 0.038) and symptomatic time to progression (P = 0.022).
      CONCLUSION: Contrary to ADC and D, the perfusion fraction f is a valuable marker
      of sorafenib treatment in advanced HCC.

PMID- 20683598
TI  - The significance of conventional radiographic parameters in the diagnosis of
      scapholunate ligament lesions.
AB  - OBJECTIVE: Although in widespread clinical use, evidence of the diagnostic
      accuracy of radiographic parameters for the diagnosis of scapholunate ligament
      injuries is scarce. The objective of this study was to evaluate the scapholunate
      (SL) angle, radiolunate (RL) angle and SL gap as diagnostic parameters for these
      lesions. METHODS: Eight hundred forty nine patients, who underwent wrist
      arthroscopy at our institution because of wrist pain were included in a
      retrospective analysis. In all patients the SL angle, RL angle and SL gap were
      measured on preoperative radiographs. These parameters were correlated with the
      actual finding of the SL ligament during arthroscopy. Optimal test thresholds
      were calculated as well as sensitivity, specificity and the likelihood ratios of
      each parameter. RESULTS: All three parameters proved useful in statistical
      analysis. The optimal cut-off points for diagnosing lesions of the SL ligament
      were calculated as 62.5 degrees  for the SL angle, 12.5 degrees  for the RL angle
      and 2.5 mm for the SL gap. SL angles had the greatest specificity (0.93).
      CONCLUSIONS: We were able to validate plain radiographs as a reliable tool in the
      work-up of patients with suspected SL ligament injuries. However, wrist
      arthroscopy remains the gold standard in diagnosing and treating these lesions.

PMID- 20683599
TI  - Positive contrast visualization of SPIO-labeled pancreatic islets using echo
      dephased steady-state free precession.
AB  - OBJECTIVE: MRI has recently been introduced as a promising method of monitoring
      the transplanted pancreatic islets labelled with superparamagnetic iron oxide
      (SPIO). However, the traditional [Formula: see text]-weighted approach frequently
      yields ambiguous results because of the negative contrast of the SPIO particles
      on the background of other body components. This obstacle could be overcome with
      the use of a novel method known as echo-dephased steady state free precession
      (SSFP), generating positive contrast in the presence of paramagnetic material.
      METHODS: In phantoms, we achieved exact localisation and clear positive contrast
      visualisation of human SPIO labelled islets. Using the proposed method we
      demonstrated the ability to detect even a single pancreatic islet against a
      homogeneous background. RESULTS: In vivo experiments in rats confirmed reliable
      and accurate localisation of transplanted SPIO labelled islets. CONCLUSION: The
      echo-dephased SSFP technique could successfully visualise SPIO-labelled human and
      rat pancreatic islets yielding a positive contrast.

PMID- 20683600
TI  - Conspicuity of breast cancer according to histopathological type and breast
      density when imaged by full-field digital mammography compared with screen-film
      mammography.
AB  - OBJECTIVES: To compare the conspicuity of different histopathological types of
      breast cancer according to breast density and mammographic imaging in patients
      with screen-detected breast cancers undergoing both full-field digital
      mammography (FFDM) and screen-film mammography (SFM) in the United Kingdom
      National Health Service Breast Screening Programme (NHSBSP). METHODS: 185
      patients underwent routine screening with SFM followed by further imaging using
      FFDM with consequent diagnosis of breast cancer. All SFM and soft-copy FFDM
      images were evaluated by two readers in an independent, retrospective review. The
      visualisation and conspicuity of the mammographic abnormality were recorded and
      graded using a four-level scale. Conspicuity of breast cancer was qualitatively
      evaluated. Breast density and conspicuity were correlated with histopathological
      diagnosis and inter-observer correlation was calculated. RESULTS: Mixed Model
      ANOVA demonstrated significant differences between FFDM and SFM (p<0.001) and
      breast densities (p=0.009): conspicuity of the mammographic abnormality (p<0.001)
      and visualisation of the dominant mammographic feature (p<0.001) were
      significantly greater with FFDM than SFM. This held true for both readers and for
      all histopathological tumour types with no significant differences between each
      tumour type. CONCLUSION: FFDM is significantly superior to SFM for conspicuity of
      screen-detected breast cancers for all histopathological types and breast
      densities.

PMID- 20683601
TI  - [Diabetic retinopathy: comparison of the diagnostic features of ultra-widefield
      scanning laser ophthalmoscopy Optomap with ETDRS 7-field fundus photography].
AB  - OBJECTIVE: The aim of the study was to compare the diagnostic properties of a non
      mydriatic 200 degrees  ultra-widefield scanning laser ophthalmoscope (SLO) with
      mydriatic ETDRS 7-field fundus photography for diabetic retinopathy screening.
      METHODS: A consecutive series of 66 eyes from 34 patients with different levels
      of diabetic retinopathy (DR) were examined. Grading of DR and macular edema (ME)
      obtained from mydriatic ETDRS 7-field fundus photography were compared with
      grading obtained from Optomap Panoramic 200MA SLO images. All SLOs were performed
      with an undilated pupil and no additional clinical information was used for
      evaluation of images by two independent, masked experts. RESULTS: A total of 14
      eyes from ETDRS 7-field fundus photography and 11 eyes from Optomap could not be
      graded by at least one grader due to poor image quality, yielding 48 eyes for
      comparison purposes. Of the 48 ETDRS 7-field fundus photographs, 9 (11 for grader
      2) eyes had no or mild DR (ETDRS levels <=20) and 17 (23 for grader 2) eyes had
      no ME. Agreement of Optomap retinopathy grading with ETDRS 7-field fundus
      photography was good, kappa 0.70 for grader 1 and kappa 0.66 for grader 2. There
      was good agreement between both techniques for ME, grader 1 kappa 0.68 and grader
      2 kappa 0.74. CONCLUSIONS: Grading of DR levels from Optomap Panoramic 200MA non
      mydriatic images showed a good correlation with mydriatic ETDRS 7-field fundus
      photography. Both techniques are of sufficient quality for a valid assessment of
      DR. Optomap Panoramic 200MA images cover a larger retinal area and might
      therefore offer additional diagnostic properties.

PMID- 20683602
TI  - Vaginal hysterectomy with bipolar coagulation forceps (BiClamp) as an alternative
      to the conventional technique.
AB  - PURPOSE: The aim was to identify the advantages and disadvantages of using
      bipolar coagulation forceps in vaginal hysterectomy and to compare the effects of
      this method with those of the conventional technique. METHODS: A group of 30
      patients was operated on with bipolar coagulation forceps and the next 30 were
      operated on using the traditional method. The following parameters were observed:
      duration of procedure, blood loss, complications, postoperative pain,
      hospitalization time and cost of treatment. RESULTS: The duration of the surgical
      procedure and hospitalization time were similar in both groups. Blood loss was
      lower in the BiClamp group. There were no serious complications in either group.
      In one case with BiClamp, laparotomy was performed to stop persistent bleeding;
      the after-effects of the laparotomy were not statistically significant. The
      patients in the BiClamp group reported less pain, experienced shorter
      recuperation times and incurred lower treatment costs. CONCLUSIONS: The BiClamp
      technique is a good alternative to traditional hysterectomy methods as it causes
      lower blood loss during surgery, causes less post-operative pain and is
      economically more favorable for the patient and hospital.

PMID- 20683603
TI  - Inhibin/activin-betaC subunit does not represent a prognostic parameter in human
      endometrial cancer.
AB  - INTRODUCTION: Inhibins, dimeric peptide hormones composed of an alpha subunit and
      one of two possible beta subunits (betaA or betaB), exhibit substantial roles in
      human reproduction and in endocrine-responsive tumors. Recently, two novel
      inhibin-beta subunits, defined as betaC and betaE, have been identified in
      humans. However, the prognostic significance and clinical implications of the
      novel inhibin-betaC subunit in endometrial cancers is still quite unclear.
      MATERIALS AND METHODS: A series of 296 uterine endometrial carcinomas were
      immunohistochemically analyzed with specific antibody against the inhibin-betaC
      subunit. The staining reactions were correlated with several clinicopathological
      characteristics and the clinical outcome. RESULTS: Endometrial cancer tissue
      demonstrated an immunolabelling against the inhibin-betaC subunit. The inhibin
      betaC expression in endometrial carcinoma samples revealed a significant
      association with hemangiosis. However, the expression of this inhibin subunit did
      not affect patients' progression-free, cause-specific and overall survival.
      CONCLUSION: Overall, inhibin-betaC subunit was demonstrated in endometrial cancer
      tissue. This novel betaC subunit demonstrated a significant association with
      hemangiosis although without any impact on the patients' survival. Moreover, the
      inhibin-betaC subunits did not constitute an independent prognostic parameter in
      endometrial cancer patients. Therefore, the isolated analysis of this subunit
      might be of minor prognostic value in identifying high-risk patients.

PMID- 20683604
TI  - Clinical evaluation of women with PMB. Is it always necessary an endometrial
      biopsy to be performed? A review of the literature.
AB  - BACKGROUND: Endometrial carcinoma is the most distressing cause of abnormal
      vaginal bleeding. The intention of clinical management in the case of
      postmenopausal bleeding is to achieve an accurate diagnosis without
      overinvestigation. METHOD: We studied the available literature on the diagnostic
      evaluation of postmenopausal women with vaginal bleeding, accentuating the most
      important aspects on this topic: the accuracy of sonography and endometrial
      biopsy in predicting endometrial hyperplasia and endometrial carcinoma. RESULTS:
      The accuracy of the above tests in predicting endometrial hyperplasia and
      endometrial carcinoma is a subject of continuing debate. MUomicronreover, in the
      last decades, there has been an explosion of publications indicating that
      ultrasound may be useful in predicting endometrial pathology. CONCLUSION: Since
      advanced endometrial carcinoma has been known to occur in cases without
      noticeable endometrial thickness on ultrasound, the clinician should beware of
      the diagnostic evaluation of postmenopausal women with vaginal bleeding.

PMID- 20683605
TI  - Predictive value of fluorodeoxyglucose uptake in head and neck cancer: importance
      of standardization: editorial on EAORL-D-10-00277.

PMID- 20683606
TI  - Sensory neuropathy in patients with cryoglobulin negative hepatitis-C infection.
AB  - There is growing evidence that hepatitis-C virus (HCV) infection might cause
      peripheral neuropathy. We aimed to investigate the prevalence, clinical and
      electrophysiological features of sensory neuropathy in patients with cryoglobulin
      negative HCV infection. We studied 46 consecutive cryoglobulin negative HCV
      positive patients (24 of them with and 22 without neuropathic symptoms, NS) and
      compared to 28 age and gender matched controls. In all patients and controls,
      clinical neuropathy symptom (NSS) and neuropathy deficit scores (NDS) were
      assessed and standard nerve conduction velocity (SNCV) and pain related-evoked
      potentials (PREP) were recorded. Both, SNCV and PREP were abnormal in 13 NS
      positive patients (13/46, 28%). Abnormal PREP but normal SNCV were found in 5
      (5/46, 11%) NS positive and in 2 NS negative patients (2/46, 4%). PREP
      abnormalities correlated positive with both clinical neuropathy scores (NSS
      r=0.62; p<0.001; NDS r=0.57; p<0.001), but not with the duration of the disease,
      current viral load, or the virus subtype. PREP abnormalities were more frequent
      (16/33, 48.5%) in HCV patients treated with interferon than in therapy naive
      patients (4/13, 30.8%); the difference was, however, not significant. In our
      present study (1) all virus subtypes are capable of inducing neuropathy, (2) no
      differences were found between interferon therapy and treatment naive patients,
      (3) the prevalence of peripheral sensory neuropathy including small sensory
      fibers (20/46, 43.5%) is higher than previously reported and (4) we found that
      detection of HCV associated neuropathy depends on the evaluation method.

PMID- 20683607
TI  - Urodynamic analysis in multiple system atrophy: characterisation of detrusor
      sphincter dyssynergia.
AB  - In multiple system atrophy (MSA), parkinsonism and a cerebellar syndrome are
      associated with autonomic dysfunction. Both bladder neck dysfunction and external
      sphincter denervation have been implicated in detrusor-sphincter dyssynergia.
      However, urethral dysfunction may not be adequately reflected by a single global
      measurement of urethral pressure. Pressure assessment at several levels of the
      urethra is needed to unravel the mechanisms of bladder-urethra dysfunction. Here,
      we evaluated the use of multiple sensor pressure transducers to assess bladder
      sphincter function in 52 patients with MSA in comparison to patients with
      Parkinson's disease (PD) who were matched for age and severity in the "off"
      condition. Urinary dysfunction appeared significantly earlier in MSA (<2 years)
      than in PD (>5 years). Detrusor under-activity with dysuria was observed in 58%
      of MSA patients within 4 years and in 76% of patients thereafter. Detrusor
      urethral dyssynergia in MSA patients was always better characterized by multiple
      sensor pressure transducer measurement of bladder and urethral pressure than by a
      single global measurement. This new approach may prove useful for differential
      diagnosis of parkinsonian syndromes, and especially MSA.

PMID- 20683608
TI  - Transcription-dependent rearrangements of actin and nuclear myosin I in the
      nucleolus.
AB  - Nuclear actin and nuclear myosin I (NMI) are important players in transcription
      of ribosomal genes. Transcription of rDNA takes place in highly organized
      intranuclear compartment, the nucleolus. In this study, we characterized the
      localization of these two proteins within the nucleolus of HeLa cells with high
      structural resolution by means of electron microscopy and gold-immunolabeling. We
      demonstrate that both actin and NMI are localized in specific compartments within
      the nucleolus, and the distribution of NMI is transcription-dependent. Moreover,
      a pool of NMI is present in the foci containing nascent rRNA transcripts. Actin,
      in turn, is present both in transcriptionally active and inactive regions of the
      nucleolus and colocalizes with RNA polymerase I and UBF. Our data support the
      involvement of actin and NMI in rDNA transcription and point out to other
      functions of these proteins in the nucleolus, such as rRNA maturation and
      maintenance of nucleolar architecture.

PMID- 20683609
TI  - High-intensity interval training improves VO(2peak), maximal lactate
      accumulation, time trial and competition performance in 9-11-year-old swimmers.
AB  - Training volume in swimming is usually very high when compared to the relatively
      short competition time. High-intensity interval training (HIIT) has been
      demonstrated to improve performance in a relatively short training period. The
      main purpose of the present study was to examine the effects of a 5-week HIIT
      versus high-volume training (HVT) in 9-11-year-old swimmers on competition
      performance, 100 and 2,000 m time (T(100 m) and T(2,000 m)), VO(2peak) and rate
      of maximal lactate accumulation (Lac(max)). In a 5-week crossover study, 26
      competitive swimmers with a mean (SD) age of 11.5 +/- 1.4 years performed a
      training period of HIIT and HVT. Competition (P < 0.01; effect size = 0.48) and
      T(2,000 m) (P = 0.04; effect size = 0.21) performance increased following HIIT.
      No changes were found in T(100 m) (P = 0.20). Lac(max) increased following HIIT
      (P < 0.01; effect size = 0.43) and decreased after HVT (P < 0.01; effect size =
      0.51). VO(2peak) increased following both interventions (P < 0.05; effect sizes =
      0.46-0.57). The increases in competition performance, T(2,000 m), Lac(max) and
      VO(2peak) following HIIT were achieved in significantly less training time (~2
      h/week).

PMID- 20683610
TI  - Excessive skeletal muscle recruitment during strenuous exercise in McArdle
      patients.
AB  - We compared the cardiorespiratory response and muscle recruitment [as determined
      by electromyography (EMG)] of 37 McArdle patients [19 males, 37.4 +/- 2.8 years,
      body mass index (BMI): 25.1 +/- 4.7 kg m(-2)] and 33 healthy controls (18 males,
      36.4 +/- 10.0 years, BMI: 25.7 +/- 3.8 kg m(-2)) during cycle-ergometer exercise
      (an incremental test to exhaustion and a 12-min submaximal constant workload
      test). We obtained cardiorespiratory [oxygen uptake and heart rate (HR)] and EMG
      data (rectus femoris and vastus lateralis muscles). During the incremental test,
      the patients exhibited the expected hyperkinetic cardiovascular response shown by
      a marked increase in the slope of the HR:Power relationship (p < 0.001).
      Throughout the incremental test and at the point of fatigue, the patients
      produced significantly less power than the controls (peak power output: 67 +/- 21
      vs. 214 +/- 56 watts respectively, p < 0.001), yet they demonstrated
      significantly higher levels of muscle activity for a given absolute power. During
      the constant workload test, patients displayed higher levels of EMG activity than
      the controls during the second half of the test, despite a lower power production
      (34 +/- 13 vs. 94 +/- 29 watts respectively, p < 0.001). In conclusion, since the
      McArdle patients required more motor unit recruitment for a given power output,
      our data suggest that the state of contractility of their muscles is reduced
      compared with healthy people. Excessive muscle recruitment for a given load could
      be one of the mechanisms explaining the exercise intolerance of these patients.

PMID- 20683611
TI  - Changes in tendon stiffness and running economy in highly trained distance
      runners.
AB  - The purpose of this study was to determine if changes in triceps-surae tendon
      stiffness (TST K) could affect running economy (RE) in highly trained distance
      runners. The intent was to induce increased TST K in a subgroup of runners by an
      added isometric training program. If TST K is a primary determinant of RE, then
      the energy cost of running (EC) should decrease in the trained subjects. EC was
      measured via open-circuit spirometry in 12 highly trained male distance runners,
      and TST K was measured using ultrasonography and dynamometry. Runners were
      randomly assigned to either a training or control group. The training group
      performed 4 * 20 s isometric contractions at 80% of maximum voluntary
      plantarflexion moment three times per week for 8 weeks. All subjects (V(O)2(max))
      = 67.4 +/- 4.6 ml kg(-1) min(-1)) continued their usual training for running. TST
      K was measured every 2 weeks. EC was measured in both training and control groups
      before and after the 8 weeks at three submaximal velocities, corresponding to 75,
      85 and 95% of the speed at lactate threshold (sLT). Isometric training did
      neither result in a mean increase in TST K (0.9 +/- 25.8%) nor a mean improvement
      in RE (0.1 +/- 3.6%); however, there was a significant relationship (r(2) = 0.43,
      p = 0.02) between the change in TST K and change in EC, regardless of the
      assigned group. It was concluded that TST K and EC are somewhat labile and change
      together.

PMID- 20683612
TI  - Learning of timing patterns and the development of temporal expectations.
AB  - The present study investigated the learning of a culturally unfamiliar musical
      rhythm, leading to the development of temporal expectations, and it explored the
      potential for generalization across tempi and tasks. With that aim, we adapted
      the serial reaction time task to examine the learning of temporal structures by
      an indirect method. The temporal pattern employed was based on a complex interval
      ratio (2:3) and compared to one based on a simple interval ratio (1:2). In the
      exposure phase, non-musician participants performed a two-choice speeded
      discrimination task that required responding by key press to each event of the
      simple or complex auditory pattern. Participants were not informed about the
      temporal regularities; their task solely concerned the discrimination task.
      During exposure (Experiments 1-3), response times decreased over time for both
      temporal patterns, but particularly for the events following the longer interval
      of the more complex 2:3 pattern. Exposure further influenced performance in
      subsequent testing phases, notably the precision of tap timing in a production
      task (Experiment 2) and temporal expectations in a perception task (Experiment
      3). Our findings promote the new paradigm introduced here as a method to
      investigate the learning of temporal structures.

PMID- 20683614
TI  - Prevalence of pediculosis capitis among Korean children.
AB  - Pediculus humanus capitis is an ectoparasite, which causes scalp pruritus
      particularly among children. A total of 15,373 children including 8,018 boys and
      7,355 girls from 26 primary schools and 15 kindergartens attached to the primary
      schools and a total of 33 children from an orphanage were examined for head lice
      infestation (HLI). The overall prevalence of HLI in this study was 4.1% including
      3.7% of the urban areas and 4.7% of the rural areas. Head lice were found more
      frequently in girls than in boys with prevalence of 6.5% and 1.9%, respectively.
      The infestation rate by school grade was 3.2%, 4.7%, 4.2%, 5.0%, 4.9%, 3.8%, and
      2.1% for kindergarten, first, second, third, fourth, fifth, and sixth grades,
      respectively. The infestation rate of the children in an orphanage was 66.7%. The
      prevalence of HLI has decreased especially in the rural areas. However, HLI is a
      still health problem of kindergarteners and primary schoolchildren in Korea.

PMID- 20683615
TI  - The non-regular orbit: three satellite DNAs in Drosophila martensis (buzzatii
      complex, repleta group) followed three different evolutionary pathways.
AB  - The genome of species from the buzzatii cluster (buzzatii complex, repleta group)
      is hosted by a number of satellite DNAs (satDNAs) showing contrasting structural
      characteristics, genomic organization and evolution, such as pBuM-alpha (~190 bp
      repeats), pBuM-alpha/beta (~370 bp repeats) and the DBC-150 (~150 bp repeats). In
      the present study, we aimed to investigate the evolution of these three satDNAs
      by looking for homologous sequences in the genome of the closest outgroup
      species: Drosophila martensis (buzzatii complex). After PCR, we isolated and
      sequenced 9 alpha, 8 alpha/beta and 11 DBC-150 sequences from this species. The
      results were compared to all pBuM and DBC-150 sequences available in literature.
      After D. martensis split from the buzzatii cluster some 6 Mya, the three satDNAs
      evolved differently in the genome of D. martensis by: (1) maintenance of a
      collection of major types of ancestral repeats in the genome (alpha); (2)
      fixation for a single major type of ancestral repeats (alpha/beta) or (3)
      fixation for new divergent species-specific repeat types (DBC-150). Curiously, D.
      seriema and D. martensis, although belonging to different and allopatric
      clusters, became independently fixed for the same major type of alpha/beta
      ancestral repeats, illustrating a rare case of parallelism in satDNA evolution.
      The contrasting pictures illustrate the diversity of evolutionary pathways a
      satDNA can follow, defining a "non-regular orbit" with outcomes difficult to
      predict.

PMID- 20683616
TI  - Pentraxins in innate immunity: lessons from PTX3.
AB  - The innate immune system constitutes the first line of defence against
      microorganisms and plays a primordial role in the activation and regulation of
      adaptive immunity. The innate immune system is composed of a cellular arm and a
      humoral arm. Components of the humoral arm include members of the complement
      cascade and soluble pattern recognition molecules (PRMs). These fluid-phase PRMs
      represent the functional ancestors of antibodies and play a crucial role in the
      discrimination between self, non-self and modified-self. Moreover, evidence has
      been presented that these soluble PRMs participate in the regulation of
      inflammatory responses and interact with the cellular arm of the innate immune
      system. Pentraxins consist of a set of multimeric soluble proteins and represent
      the prototypic components of humoral innate immunity. Based on the primary
      structure of the protomer, pentraxins are divided into two groups: short
      pentraxins and long pentraxins. The short pentraxins C-reactive protein and serum
      amyloid P-component are produced by the liver and represent the main acute phase
      proteins in human and mouse, respectively. The long pentraxin PTX3 is produced by
      innate immunity cells (e.g. PMN, macrophages, dendritic cells), interacts with
      several ligands and plays an essential role in innate immunity, tuning
      inflammation and matrix deposition. PTX3 provides a paradigm for the mode of
      action of humoral innate immunity.

PMID- 20683617
TI  - Performance evaluation and kinetic modeling of the start-up of a UASB reactor
      treating municipal wastewater at low temperature.
AB  - A kinetic modeling-based study was carried out to evaluate the start-up
      performance of a 10-L up-flow anaerobic sludge blanket (UASB) reactor treating
      municipal wastewater under different organic and hydraulic loading conditions.
      The reactor was operated for 105 days (around 4 months) below 20  degrees C and
      with three different hydraulic retention times of 24, 12 and 5 h. Imposed
      volumetric organic loading rates (OLR) ranged from 0.57 (+/-0.05) to 11.78 (+/
      0.85) kg TCOD/m(3)-day. Although relatively high incoming volumetric OLR values
      were employed to the system, the UASB reactor demonstrated a favorable
      performance on the anaerobic treatability of municipal wastewater, and no process
      failure was recorded in the start-up stage. On the basis of experimental results,
      the modified Stover-Kincannon model was successfully applied to define the start
      up kinetics with a very high value of the correlation coefficient (R = 0.9729).
      Maximum substrate utilization rate constant and saturation constant of the
      modified Stover-Kincannon model were determined as U (max) = 1.996 g/L-day and K
      (B) = 1.536 g/L-day, respectively.

PMID- 20683618
TI  - Similar renal outcomes in children with ADPKD diagnosed by screening or
      presenting with symptoms.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) in children is sometimes
      considered to be a benign condition, with morbidity manifesting in adulthood.
      Therefore, diagnostic screening of children at risk is controversial. The aim of
      our study was to to compare the manifestations of ADPKD in children diagnosed by
      postnatal ultrasound (US) screening versus those presenting with symptoms. This
      was a retrospective chart review of children with ADPKD assessed in a single
      centre between 1987 and 2007. Age and reason for diagnosis were noted, and
      children were separated into two groups: (1) those diagnosed on the basis of
      family-based screening; (2) those presenting with a symptom. The two groups were
      compared for renal size, number of cysts, estimated glomerular filtration rate
      (eGFR), the presence of hypertension and microalbuminuria. In the 47 children
      with ADPKD (21 females) from 33 families who satisfied the enrollment criteria,
      mean (standard deviation) age at referral and last follow-up was 7.2 (4.4) and
      12.9 (5.1) years, respectively, and the mean follow-up duration was 5.7 (3.6)
      years. Diagnosis was based on postnatal US screening in 31 children, whereas 16
      were diagnosed after presenting with symptoms. The proportions of children with
      nephromegaly, hypertension, microalbuminuria and decreased eGFR, respectively,
      were similar in both groups. Based on these results, we conclude that renal
      related morbidities, including hypertension and microalbuminia, do occur in
      children with ADPKD and at a similar frequency in those diagnosed after
      presenting with symptoms and those diagnosed upon postnatal screening. We suggest
      that at-risk children should have regular checks to detect hypertension.
      Moreover, affected children may benefit from novel therapies to minimise cystic
      disease progression.

PMID- 20683619
TI  - Urinary monocyte chemoattractant protein-1 correlates with disease activity in
      lupus nephritis.
AB  - Monocyte chemoattractant protein-1 (MCP-1) has a pathogenic role in murine lupus
      nephritis (LN). We recruited 25 pediatric and adolescent systemic lupus
      erythematosus (SLE) patients from our lupus clinic [13 (52%) patients with LN and
      12 (48%) lupus non-nephritis patients] and evaluated their urinary and plasma MCP
      1 levels compared to adult and childhood controls. The median age and SLE disease
      duration of patients were 14.4 and 5.5 years, respectively. LN patients had a
      higher median renal (p=0.01) British Isles Lupus Assessment Group (BILAG) index,
      with a tendency for higher total BILAG scores (p=0.2). There were significantly
      increased urinary MCP-1 levels in the LN patients compared to healthy controls
      (p<0.001) whose values were significantly higher than lupus non-nephritis
      children (p<0.004). Urinary MCP-1 levels correlated well with total BILAG scores
      (r=0.82, p=0.04). There were no differences in plasma MCP-1 levels between SLE
      patient groups and pediatric controls, although the levels in the childhood
      controls were elevated compared to those of the adult controls (p<0.04). These
      results provide evidence of increased urinary--but not plasma--MCP-1 levels in
      children with LN, which correlates well with SLE disease activity as measured by
      the BILAG index.

PMID- 20683620
TI  - Modeled response of the West Nile virus vector Culex quinquefasciatus to changing
      climate using the dynamic mosquito simulation model.
AB  - Climate can strongly influence the population dynamics of disease vectors and is
      consequently a key component of disease ecology. Future climate change and
      variability may alter the location and seasonality of many disease vectors,
      possibly increasing the risk of disease transmission to humans. The mosquito
      species Culex quinquefasciatus is a concern across the southern United States
      because of its role as a West Nile virus vector and its affinity for urban
      environments. Using established relationships between atmospheric variables
      (temperature and precipitation) and mosquito development, we have created the
      Dynamic Mosquito Simulation Model (DyMSiM) to simulate Cx. quinquefasciatus
      population dynamics. The model is driven with climate data and validated against
      mosquito count data from Pasco County, Florida and Coachella Valley, California.
      Using 1-week and 2-week filters, mosquito trap data are reproduced well by the
      model (P < 0.0001). Dry environments in southern California produce different
      mosquito population trends than moist locations in Florida. Florida and
      California mosquito populations are generally temperature-limited in winter. In
      California, locations are water-limited through much of the year. Using future
      climate projection data generated by the National Center for Atmospheric Research
      CCSM3 general circulation model, we applied temperature and precipitation offsets
      to the climate data at each location to evaluate mosquito population sensitivity
      to possible future climate conditions. We found that temperature and
      precipitation shifts act interdependently to cause remarkable changes in modeled
      mosquito population dynamics. Impacts include a summer population decline from
      drying in California due to loss of immature mosquito habitats, and in Florida a
      decrease in late-season mosquito populations due to drier late summer conditions.

PMID- 20683621
TI  - The cancer stem cell marker CD133 is a predictor of the effectiveness of S1+
      pegylated interferon alpha-2b therapy against advanced hepatocellular carcinoma.
AB  - BACKGROUND: Combination therapy with the oral fluoropyrimidine anticancer drug S1
      and interferon is reportedly effective for the treatment of advanced
      hepatocellular carcinoma (HCC), but selection criteria for this therapy have not
      been clarified. In this study, we attempted to identify factors predicting the
      effectiveness of this combination therapy. METHODS: Pathological specimens of HCC
      were collected before treatment from 31 patients with advanced HCC who underwent
      S1+ pegylated-interferon (PEG-IFN) alpha-2b therapy between January 2007 and
      January 2009. In these pathological specimens, the expression levels of CD133,
      thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and interferon
      receptor 2 (IFNR2) proteins were determined by Western blot assay. The presence
      or absence of p53 gene mutations was determined by direct sequencing. The
      relationships between these protein expression levels and the response rate (RR),
      progression-free survival (PFS), and overall survival (OS) were evaluated.
      RESULTS: The CD133 protein expression level was significantly lower in the
      responder group than in the nonresponder group. Comparing the PFS and OS between
      high- and low-level CD133 expression groups (n = 13 and 18, respectively)
      revealed that both parameters were significantly prolonged in the latter group.
      The expression levels of TS, DPD, and IFNR2 protein and the presence of p53 gene
      mutations did not correlate with the RR. CONCLUSIONS: CD133 was identified as a
      predictor of the therapeutic effect of S1+ PEG-IFN alpha-2b therapy against
      advanced HCC.

PMID- 20683622
TI  - Laparoscopic partial splenectomy using a detachable clamp with and without
      partial splenic embolisation.
AB  - BACKGROUND: In many centres, the laparoscopic total splenectomy is a well
      established routine procedure. However, the crucial immunological role of the
      spleen in combating bacterial infections, in particular pneumonias, has led to a
      search for splenic-preserving techniques whenever possible. Yet, laparoscopic
      partial splenectomies are still rarely described possibly due to difficulties in
      controlling intra-operative parenchymal bleeding during splenic transection.
      METHODS: Here, we present a case series of laparoscopic partial splenectomies
      using a new technique. The main splenic artery and vein were temporarily clamped
      using a detachable clip. Transection of the spleen was possible working with the
      LigaSureTM instrument. After transection, the margin was sealed with a collagen
      fleece. In one case of a haemangioma, the patient underwent a radiological coil
      embolisation of the feeding arteries of the splenic pole in question. This was
      done 4 weeks prior to surgery and included embolisation of the tumour. RESULTS:
      Three patients (2 males, 1 female, mean age 58.3 years) have been successfully
      treated using a detachable clamp. The pre-surgical mean size of the spleen was
      8.0 * 16.7 cm (range 6 * 14-11 * 22 cm). The removed specimens had a mean size of
      4.2 * 5.5 cm (range 2.5 * 4.0-5.0 * 6.5 cm). The time of surgery averaged 144 min
      (range 110-187 min). Blood loss was minimal thereby avoiding the need for blood
      transfusions. The post-surgical course was uneventful; patients were discharged 5
      days following surgery. Histopathology showed a benign splenic haemangioma, a
      benign splenic hamartoma and the presence of Hodgkin's disease stage III.
      CONCLUSIONS: The technique of laparoscopic partial splenectomy and, in certain
      patients, pre-surgical partial splenic embolisation is safe and effective for
      patients with localised diseases of the spleen. This approach combines the
      benefits of the minimal surgical access with saving a significant amount of
      splenic tissue, thereby preserving the immune function of the spleen.

PMID- 20683623
TI  - Familial nonmedullary thyroid carcinoma-clinical relevance and prognosis. A
      European multicenter study. ESES Vienna presentation.
AB  - PURPOSE: Approximately 5% of differentiated thyroid carcinomas are of familial
      origin. These familial nonmedullary thyroid carcinomas (FNMTC) have an increased
      risk of multifocal disease and lymph node involvement. Consequently, higher
      recurrence rates and decreased disease-specific survival rates are described. The
      best surgical approach is discussed controversially. PATIENTS AND METHODS: A
      survey among the international members of the German Society of Endocrine
      Surgeons revealed 20 families with two or more first-degree relatives with FNMTC.
      The mean age of the 41 patients (30 female, 11 male) with FNMTC was 40.6 years
      (18-73 years). RESULTS: Total thyroidectomy was performed in 31 of 41 patients
      (76%). Ninety-five percent of the tumors were papillary carcinomas. Two of 41
      patients had follicular carcinomas. Ten patients (24%) with papillary carcinomas
      were diagnosed with Hashimoto's thyroiditis. The mean tumor size was 1.45 cm.
      FNMTC was multifocal in 12 patients (29%). A systematic lymph node dissection was
      performed in 21 of 41 patients (51%). Lymph nodes metastases were found in seven
      of these 21 patients. Twenty-eight of the patients (68%) underwent postoperative
      radioiodine ablation. After a mean follow-up of 7.2 years, 39 patients (95%) were
      disease free. One patient developed local recurrence and lung metastases, 10 and
      25 years, respectively, after initial diagnosis. Another patient died 2 years
      postoperatively from advanced metastatic disease. CONCLUSIONS: FNMTC is
      associated with an early onset of small, mostly papillary thyroid carcinomas and
      an increased risk of multifocality and lymph node involvement. Total
      thyroidectomy and systematic neck dissection are recommended together with
      radioiodine ablation. Screening for first-degree relatives should start at age 18
      years.

PMID- 20683625
TI  - Dynamic stabilization adjacent to single-level fusion: part I. Biomechanical
      effects on lumbar spinal motion.
AB  - Progression of superior adjacent segment degeneration (PASD) could possibly be
      avoided by dynamic stabilization of an initially degenerated adjacent segment
      (AS). The current study evaluates ex vivo the biomechanics of a circumferential
      fixation connected to posterior dynamic stabilization at the AS. 6 human cadaver
      spines (L2-S1) were stabilized stepwise through the following conditions for
      comparison: intact spine (ISP), single-level fixation L5-S1 (SLF), SLF + dynamic
      AS fixation L4-L5 (DFT), and two-level fixation L4-S1 (TLF). For each condition,
      the moments required to reach the range of motion (ROM) of the intact whole spine
      segment under +/-10 Nm (WSP10) were compared for all major planes of motion
      within L2-S1. The ROM at segments L2/3, L3/4, and L4/5 when WSP10 was applied
      were also compared for each condition. The moments needed to maintain WSP10
      increased with each stage of stabilization, from ISP to SLF to DFT to TLF (p <
      0.001), in all planes of motion within L2-S1. The ROM increased in the same order
      at L3/4 (extension, flexion, and lateral bending) and L2/3 (all except right
      axial rotation, left lateral bending) during WSP10 application with 300 N axial
      preload (p < 0.005 in ANOVA). At L4/5, while applying WSP10, all planes of motion
      were affected by stepwise stabilization (p < 0.001): ROM increased from ISP to
      SLF and decreased from SLF to DFT to TLF (partially p < 0.05). The moments
      required to reach WSP10 increase dependent on the number of fixated levels and
      the fixation stiffness of the implants used. Additional fixation shifts motion to
      the superior segment, according to fixation stiffness. Therefore, dynamic
      instrumentation cannot be recommended if prevention of hyper-mobility in the
      adjacent levels is the main target.

PMID- 20683626
TI  - Negative correlation between serum syndecan-1 and apolipoprotein A1 in patients
      with type 2 diabetes mellitus.
AB  - Heparan sulfate proteoglycans (HSPGs) are involved in the regulation of cell
      growth, apoptosis and lipid metabolism in vitro. Syndecans are the primary form
      of HSPGs. Syndecan-1 is involved in the processes of cell growth,
      differentiation, adhesion, wound healing and inflammation. Additionally, as a
      sinusoidal transmembrane HSPG facing the plasma compartment, syndecan-1 is a
      promising target to be involved in lipoprotein physiology. We aimed to examine
      the possible correlation of syndecan-1 and lipid profile in type 2 diabetes
      mellitus. In this study, serum syndecan-1 was detected by ELISA, and potential
      correlations between syndecan-1 and triglyceride, cholesterol, low-density
      lipoprotein cholesterol, high-density lipoprotein cholesterol, lipoprotein a,
      apolipoprotein (apo) B, apoA1 and apoB/apoA1 were analyzed. Forty-one patients
      with type 2 diabetes and 31 age-matched, non-diabetic healthy subjects (controls)
      were enrolled. Syndecan-1 in patients with diabetes (26.15 +/- 2.42 ng/ml) was
      significantly higher than that of the controls (16.85 +/- 1.98 ng/ml, t = -2.98,
      P = 0.005). Serum syndecan-1 level correlated negatively with apoA1 (r = -0.46, P
      = 0.003). Multiple regression analysis showed that apoA1 (b = -0.43, P = 0.003)
      was a predictor of serum syndecan-1 levels in subjects with type 2 diabetes.

PMID- 20683624
TI  - Physiological carbon dioxide, bicarbonate, and pH sensing.
AB  - In biological systems, carbon dioxide exists in equilibrium with bicarbonate and
      protons. The individual components of this equilibrium (i.e., CO2, HCO3-, and
      H(+)), which must be sensed to be able to maintain cellular and organismal pH,
      also function as signals to modulate multiple physiological functions. Yet, the
      molecular sensors for CO2/HCO3-/pH remained unknown until recently. Here, we
      review recent progress in delineating molecular and cellular mechanisms for
      sensing CO2, HCO3-, and pH.

PMID- 20683627
TI  - Patients' evaluation of nocturnal hypoglycaemia with GlucoDay continuous glucose
      monitoring in paediatric patients.
AB  - A study was conducted to evaluate the accuracy of GlucoDay (A. Menarini
      Diagnostics) during 48 h of continuous glucose monitoring (CGMS) in type 1
      diabetic adolescents and use this novel approach to assess otherwise ignored
      nocturnal hypoglycaemias, in relationship to intermediate-acting insulin
      administration timing. Twenty type 1 diabetic adolescents with poor metabolic
      control were selected from our out-patient department. Equal doses of
      intermediate insulin were administered at 19:00 and at 22:00 of the first and
      second night of the study, respectively. Correlation coefficient between GlucoDay
      and standard glucometer was 0.94; 98.3% of data fall in the A + B area of Error
      Grid Analysis and 1.7% in the D area. The mean error was 13.9% overall and 16.4%
      with blood glucose values (BGV) <75 mg/dl. The accuracy, +/-15 mg/dl, was 82% for
      BGV <75 mg/dl and 74% for BGV >75 mg/dl. The CGMS discovered nocturnal
      hypoglycaemia (NH) in 12/18 patients, but no severe hypoglycaemia. During the
      first night, 8 asymptomatic NH episodes were found with BGV <60 mg/dl and 12 with
      BGV <80. During the second night, 4 asymptomatic NH episodes with BGV <60 mg/dl
      and 5 with BGV <80 were found. Furthermore, during the second night, the mean
      duration of BGV <126 mg/dl was lower than in the first night. GlucoDay is a
      reliable device for CGMS in paediatric patients and able to determine
      asymptomatic NH. Bedtime insulin injections provided safer glycaemic profiles and
      a lower percentage of hypoglycaemic events, representing a safer insulin
      administration scheme.

PMID- 20683628
TI  - Cytological and physiological changes related to cryotolerance in recalcitrant
      Livistona chinensis embryos during seed development.
AB  - Cytological and biochemical changes in recalcitrant Livistona chinensis embryos
      following the acquisition and loss of cryotolerance to liquid nitrogen during
      seed development were studied. The embryonic cells were always hydrated and
      contained fully functional organelles throughout seed development. However, the
      central cells in the root-epicotyl end of the embryo exhibited partial
      dedifferentiation during the middle developmental stages, although extensive
      reduction of mitochondria and vacuolation and intensive accumulation of starch
      grains, lipid, and protein bodies were not observed. Total soluble sugar content
      rose then decreased on a fresh weight and water weight basis, while soluble and
      heat-stable proteins increased in number and content then decreased, as seeds
      matured. These cytological and biochemical features differ from those of orthodox
      seeds, providing a physiological basis for the recalcitrant behavior of L.
      chinensis seeds. The changes were closely correlated with acquisition and loss of
      cryotolerance in L. chinensis embryos and are presumed to contribute to
      cryotolerance, which would account for the cryotolerance variation in L.
      chinensis embryos. Cryotolerance is suggested to be a complex, multifaceted
      process, and accumulation of soluble sugars and soluble and heat-stable proteins
      alone is not enough to increase cryotolerance per se without acting in
      combination with a decrease of cellular metabolic activity.

PMID- 20683629
TI  - A peptide mimic of the chemotaxis inhibitory protein of Staphylococcus aureus:
      towards the development of novel anti-inflammatory compounds.
AB  - Complement factor C5a is one of the most powerful pro-inflammatory agents
      involved in recruitment of leukocytes, activation of phagocytes and other
      inflammatory responses. C5a triggers inflammatory responses by binding to its G
      protein-coupled C5a-receptor (C5aR). Excessive or erroneous activation of the
      C5aR has been implicated in numerous inflammatory diseases. The C5aR is therefore
      a key target in the development of specific anti-inflammatory compounds. A very
      potent natural inhibitor of the C5aR is the 121-residue chemotaxis inhibitory
      protein of Staphylococcus aureus (CHIPS). Although CHIPS effectively blocks C5aR
      activation by binding tightly to its extra-cellular N terminus, it is not
      suitable as a potential anti-inflammatory drug due to its immunogenic properties.
      As a first step in the development of an improved CHIPS mimic, we designed and
      synthesized a substantially shorter 50-residue adapted peptide, designated CHOPS.
      This peptide included all residues important for receptor binding as based on the
      recent structure of CHIPS in complex with the C5aR N terminus. Using isothermal
      titration calorimetry we demonstrate that CHOPS has micromolar affinity for a
      model peptide comprising residues 7-28 of the C5aR N terminus including two O
      sulfated tyrosine residues at positions 11 and 14. CD and NMR spectroscopy showed
      that CHOPS is unstructured free in solution. Upon addition of the doubly sulfated
      model peptide, however, the NMR and CD spectra reveal the formation of structural
      elements in CHOPS reminiscent of native CHIPS.

PMID- 20683630
TI  - A new method for closure of large donor side defects after raising the pectoralis
      major flap.
AB  - BACKGROUND: Although free flaps are reliable for head and neck reconstructions,
      the pectoralis major flap (PMF) is still often used. In cases of a large PMF, the
      closure of the donor side can be a challenge. CASE REPORT: A technique,
      originally developed for the treatment and prevention of abdominal ruptures after
      laparotomy, is presented as an alternative for closure of large donor side
      defects. CONCLUSION: The use of Ventrofil(r) is an additional option for large
      donor side defects and especially to bridge the period of postoperative swelling.
      If utilized special attention must be paid to possible pressure necrosis of the
      underlying skin.

PMID- 20683631
TI  - MDCT appearance of the appendix: how does the low-density barium sulfate oral
      contrast agent affect it?
AB  - We compared the effect of low-density barium sulfate neutral oral contrast agent
      on the diameter of normal appendix and its luminal content versus that of water
      on multidetector-row CT. CT scans of 24 patients who had been imaged on two
      separate occasions for the evaluation of pancreatic pathology, once with water
      and subsequently with low-density barium sulfate as the neutral oral contrast
      agent were evaluated (total of 48 scans). Studies were randomized and reviewed in
      consensus on a workstation in the stack mode by two radiologists blinded to the
      type of oral contrast. The appendix was measured at baseline and 10 days later to
      obtain an average diameter. Results of the water and low-density barium sulfate
      groups were compared using paired t test. Contents of the appendiceal lumen were
      also noted (gas, fluid, mixed, and collapsed appendix). The average diameter of
      the appendix for scans obtained with water and low-density barium sulfate was
      4.09 +/- 0.87 mm (median, 4.22 mm; range, 2.50-5.65 mm) and 4.13 +/- 0.93 mm
      (median, 4 mm, range, 2.2-5.65 mm), respectively. This difference was not
      statistically significant (P = 0.69). There was no statistically significant
      difference in the appendiceal content when water or low-density barium sulfate
      were used as oral contrast (chi (2) = 4.25, P = 0.89). Low-density barium sulfate
      does not affect appendiceal content or diameter and, therefore, should not
      adversely affect evaluation of the appendix on multidetector row CT.

PMID- 20683632
TI  - Germin-like proteins (GLPs) in cereal genomes: gene clustering and dynamic roles
      in plant defence.
AB  - The recent release of the genome sequences of a number of crop and model plant
      species has made it possible to define the genome organisation and functional
      characteristics of specific genes and gene families of agronomic importance. For
      instance, Sorghum bicolor, maize (Zea mays) and Brachypodium distachyon genome
      sequences along with the model grass species rice (Oryza sativa) enable the
      comparative analysis of genes involved in plant defence. Germin-like proteins
      (GLPs) are a small, functionally and taxonomically diverse class of cupin-domain
      containing proteins that have recently been shown to cluster in an area of rice
      chromosome 8. The genomic location of this gene cluster overlaps with a disease
      resistance QTL that provides defence against two rice fungal pathogens
      (Magnaporthe oryzae and Rhizoctonia solani). Studies showing the involvement of
      GLPs in basal host resistance against powdery mildew (Blumeria graminis ssp.)
      have also been reported in barley and wheat. In this mini-review, we compare the
      close proximity of GLPs in publicly available cereal crop genomes and discuss the
      contribution that these proteins, and their genome sequence organisation, play in
      plant defence.

PMID- 20683633
TI  - Better short-term clinical response to etanercept in Chinese than Caucasian
      patients with active ankylosing spondylitis.
AB  - Tumor necrosis factor-alpha (TNF-alpha) inhibitors including etanercept have been
      demonstrated to be very effective in severe ankylosing spondylitis (AS) in
      Caucasian patients. However, clinical efficacy of etanercept to treat active AS
      in Chinese patients has not been reported. In this study, a prospective, open
      label trial of etanercept (25 mg BIW), involving 46 AS patients from 16 medical
      centers of Taiwan, was conducted. Questionnaire was utilized to record
      demographic data and clinical parameters, including Bath AS Disease Activity
      Index (BASDAI), Bath AS Functional Index (BASFI), Bath AS Global Index (BASGI),
      Assessment in Ankylosing Spondylitis (ASAS) 20, 50, and 70, and others, before
      and at different time intervals after etanercept treatment. Laboratory tests
      including blood chemistry, hematology, urine analysis, erythrocyte sedimentation
      rate (ESR), and C-reactive protein (CRP) were done at baseline and at weeks 4, 8,
      and 12. In this 12-week study, etanercept demonstrated rapid and significant
      improvement in the ASAS20 response criteria (91.3%), at as early as 2 weeks of
      therapy (71.3%). Partial remission of AS was achieved in 49.3% of patients after
      12 weeks of treatment. Disease activity (BASDAI) and function (BASFI) were also
      significantly improved after 12 weeks etanercept treatment (p < 0.0001 and p <
      0.0001, respectively). In addition, significant increase of chest expansion (2.77
      +/- 1.69 cm versus 3.56 +/- 1.82 cm, p = 0.0004) and lumbar flexion (2.11 +/-
      2.76 cm versus 2.58 +/- 3.42 cm, p = 0.0075) and significant reduction of occiput
      to-wall distance (6.59 +/- 7.14 cm versus 5.32 +/- 6.65 cm, p = 0.0006) were also
      demonstrated. Both ESR and CRP declined significantly after patients were treated
      with etanercept. There were no severe adverse effects during the treatment
      period. Etanercept is generally safe, well tolerated, and effective in Chinese
      patients with severe AS. Clinical efficacy, including partial remission and
      BASDAI, is even better in Chinese than in Caucasian patients. Further study is
      required to assess long-term efficacy and safety in Chinese patients with AS.

PMID- 20683635
TI  - Disuse-related decline in trabecular bone structure.
AB  - Sedentary life style may degrade bone mass and microstructure resulting in
      osteoporosis. We characterized trabecular bone structural properties to determine
      if the LRP5 G171V mutation will protect against disuse-related bone loss. Forty
      eight adult male mice representing three genotypes (WT = wild type, KO = LRP5
      knockout +/-, HBM = High bone with the LRP5 G171V mutation) were each randomly
      divided between control and disuse (4 week hindlimb suspension) groups.
      Trabecular bone volume fraction (BV/TV) declined in all the three genotypes.
      Trabecular thickness was lower in the HBM and LRP5 (+/-) KO disuse groups when
      compared to their respective controls. While the remaining measures of bone
      structure (Trabecular number, connectivity density, apparent and tissue density)
      were lower, the trabecular separation increased in the LRP5 (+/-) with disuse.
      Although the absolute loss in BV/TV was similar, the relative loss due to disuse
      was far greater in the LRP5 (+/-) mice (67%) than in the HBM mice (14%). The
      disuse caused 20% decrease in trabecular number and thickness for LRP5 (+/-),
      while the decline was between 6 and 11% for the HBM and WT mice.

PMID- 20683636
TI  - A low-cost procedure for production of fresh autochthonous wine yeast.
AB  - A low-cost procedure was designed for easy and rapid response-on-demand
      production of fresh wine yeast for local wine-making. The pilot plant produced
      fresh yeast culture concentrate with good microbial quality and excellent
      oenological properties from four selected wine yeasts. The best production yields
      were obtained using 2% sugar beet molasses and a working culture volume of less
      than 60% of the fermenter capacity. The yeast yield using 2% sugar grape juice
      was low and had poor cell viability after freeze storage, although the resulting
      yeast would be directly available for use in the winery. The performance of these
      yeasts in commercial wineries was excellent; they dominated must fermentation and
      improved its kinetics, as well as improving the physicochemical parameters and
      the organoleptic quality of red and white wines.

PMID- 20683637
TI  - A Phase II trial of 17-allylamino, 17-demethoxygeldanamycin (17-AAG,
      tanespimycin) in patients with metastatic melanoma.
AB  - PURPOSE: A Phase II study to screen for anti-melanoma activity of the heat shock
      protein 90 (HSP90) inhibitor, 17-AAG (17-allylamino-17-demethoxygeldanamycin) was
      performed. The primary endpoint was the rate of disease stabilisation in patients
      with progressive, metastatic melanoma treated with 17-AAG. Secondary endpoints
      were to determine: the toxicity of 17-AAG, the duration of response(s), median
      survival and further study the pharmacokinetics and pharmacodynamics of 17-AAG.
      PATIENTS AND METHODS: Patients with metastatic melanoma (progressive disease
      documented <=6 months of entering study) were treated with weekly, intravenous 17
      AAG. A Simon one sample two stage minimax design was used. A stable disease rate
      of >=25% at 6 months was considered compatible with 17-AAG having activity.
      RESULTS: Fourteen patients (8 male: 6 female) were entered, eleven received 17
      AAG (performance status 0 or 1). Median age was 60 (range 29-81) years. The
      majority (93%) received prior chemotherapy and had stage M1c disease (71%).
      Toxicity was rarely >= Grade 2 in severity and commonly included fatigue,
      headache and gastrointestinal disturbances. One of eleven patients treated with
      17-AAG had stable disease for 6 months and median survival for all patients was
      173 days. The study was closed prematurely prior to completion of the first stage
      of recruitment and limited planned pharmacokinetic and pharmacodynamic analyses.
      CONCLUSION: Some evidence of 17-AAG activity was observed although early study
      termination meant study endpoints were not reached. Stable disease rates can be
      incorporated into trials screening for anti-melanoma activity and further study
      of HSP90 inhibitors in melanoma should be considered.

PMID- 20683639
TI  - Dynamics of immunological models.
AB  - We analyse the effect of the regulatory T cells (Tregs) in the local control of
      the immune responses by T cells. We obtain an explicit formula for the level of
      antigenic stimulation of T cells as a function of the concentration of T cells
      and the parameters of the model. The relation between the concentration of the T
      cells and the antigenic stimulation of T cells is an hysteresis, that is unfold
      for some parameter values. We study the appearance of autoimmunity from cross
      reactivity between a pathogen and a self antigen or from bystander proliferation.
      We also study an asymmetry in the death rates. With this asymmetry we show that
      the antigenic stimulation of the Tregs is able to control locally the population
      size of Tregs. Other effects of this asymmetry are a faster immune response and
      an improvement in the simulations of the bystander proliferation. The rate of
      variation of the levels of antigenic stimulation determines if the outcome is an
      immune response or if Tregs are able to maintain control due to the presence of a
      transcritical bifurcation for some tuning between the antigenic stimuli of T
      cells and Tregs. This behavior is explained by the presence of a transcritical
      bifurcation.

PMID- 20683638
TI  - Enhanced production and isotope enrichment of recombinant glycoproteins produced
      in cultured mammalian cells.
AB  - NMR studies of post-translationally modified proteins are complicated by the lack
      of an efficient method to produce isotope enriched recombinant proteins in
      cultured mammalian cells. We show that reducing the glucose concentration and
      substituting glutamate for glutamine in serum-free medium increased cell
      viability while simultaneously increasing recombinant protein yield and the
      enrichment of non-essential amino acids compared to culture in unmodified, serum
      free medium. Adding dichloroacetate, a pyruvate dehydrogenase kinase inhibitor,
      further improves cell viability, recombinant protein yield, and isotope
      enrichment. We demonstrate the method by producing partially enriched recombinant
      Thy1 glycoprotein from Lec1 Chinese hamster ovary (CHO) cells using U-13C-glucose
      and 15N-glutamate as labeled precursors. This study suggests that uniformly
      15N,13C-labeled recombinant proteins may be produced in cultured mammalian cells
      starting from a mixture of labeled essential amino acids, glucose, and glutamate.

PMID- 20683640
TI  - A computational model of the circulating renin-angiotensin system and blood
      pressure regulation.
AB  - The renin-angiotensin system (RAS) is critical in sodium and blood pressure (BP)
      regulation, and in cardiovascular-renal (CVR) diseases and therapeutics. As a
      contribution to SAPHIR project, we present a realistic computer model of renin
      production and circulating RAS, integrated into Guyton's circulatory model (GCM).
      Juxtaglomerular apparatus, JGA, and Plasma modules were implemented in C ++/M2SL
      (Multi-formalism Multi-resolution Simulation Library) for fusion with GCM. Matlab
      optimization toolboxes were used for parameter identification. In JGA, renin
      production and granular cells recruitment (GCR) are controlled by perfusion
      pressure (PP), macula densa (MD), angiotensin II (Ang II), and renal sympathetic
      activity (RSNA). In Plasma, renin and ACE (angiotensin-converting enzyme)
      activities are integrated to yield Ang I and II. Model vs. data deviation is
      given as normalized root mean squared error (nRMSE; n points). IDENTIFICATION:
      JGA and Plasma parameters were identified against selected experimental data.
      After fusion with GCM: (1) GCR parameters were identified against Laragh's PRA
      natriuresis nomogram; (2) Renin production parameters were identified against two
      sets of data ([renin] transients vs. ACE or renin inhibition). Finally, GCR
      parameters were re-identified vs. Laragh's nomogram (nRMSE 8%, n = 9).
      VALIDATION: (1) model BP, PRA and [Ang II] are within reported ranges, and
      respond physiologically to sodium intake; (2) short-term Ang II infusion induces
      reported rise in BP and PRA. The modeled circulating RAS, in interaction with an
      integrated CVR, exhibits a realistic response to BP control maneuvers. This
      construction will allow for modelling hypertensive and CVR patients, including
      salt-sensitivity, polymorphisms, and pharmacotherapeutics.

PMID- 20683641
TI  - A loss-of-function mutation in Calmodulin2 gene affects pollen germination in
      Arabidopsis thaliana.
AB  - Calmodulin (CAM) is an ubiquitous calcium binding protein whose function is to
      translate the signals, perceived as calcium concentration variations, into the
      appropriate cellular responses. In Arabidopsis thaliana there are 4 CAM isoforms
      which are highly similar, encoded by 7 genes, and one possible explanation
      proposed for the evolutionary conservation of the CAM gene family is that the
      different genes have acquired different functions so that they play possibly
      overlapping but non-identical roles. Here we report the characterization of the
      Arabidopsis mutant cam2-2, identified among the lines of the gene-trapping
      collection EXOTIC because of a distorted segregation of kanamycin resistance.
      Phenotypic analysis showed that in normal growth conditions cam2-2 plants were
      indistinguishable from the wild type while genetic analysis showed a reduced
      transmission of the cam2-2 allele through the male gametophyte and in vitro
      pollen germination revealed a reduced level of germination in comparison with the
      wild type. These results provide genetic evidence of the involvement of a CAM
      gene in pollen germination and support the theory of functional diversification
      of the CAM gene family.

PMID- 20683642
TI  - SOCS3 inhibits insulin signaling in porcine primary adipocytes.
AB  - Insulin resistance is a major player in the pathogenesis of type II diabetes, the
      metabolic syndrome, and obesity. SOCS3 plays an important role in the development
      of insulin resistance. To investigate the role of SOCS3 in porcine adipocyte
      insulin signaling, we first detected the effect of insulin on SOCS3 mRNA and
      protein expression in porcine primary adipocytes by real-time RT-PCR and Western
      blotting. Then, we constructed a recombinant adenovirus encoding SOCS3 gene (Ad
      SOCS3) which was used to infect differentiated porcine primary adipocytes for 3
      days. The expression and phosphorylation of main insulin signaling components
      were detected by Western blotting. The results showed that 100 nM insulin could
      induce SOCS3 mRNA expression but not protein expression, and overexpression of
      SOCS3 decreased IRS1 protein level, insulin-stimulated IRS1 tyrosine
      phosphorylation, PI3K activation, and Akt phosphorylation, but increased IRS1
      serine phosphorylation in porcine primary adipocytes. These results indicate that
      SOCS3 is an important negative regulator of insulin signaling in porcine
      adipocytes. Thus, SOCS3 may be a novel therapeutic target for the prevention or
      treatment of insulin resistance and type II diabetes.

PMID- 20683643
TI  - MicroRNA-200b regulates cyclin D1 expression and promotes S-phase entry by
      targeting RND3 in HeLa cells.
AB  - MicroRNAs (miRNAs) are endogenous non-coding small RNAs that inhibit gene
      expression post-transcriptionally. By regulating their target genes, miRNAs play
      important roles in tumor generation and development. Recently, the mir-200 family
      was revealed to inhibit the epithelial-mesenchymal transition, which is viewed as
      an essential step in early tumor metastasis. Here, we used luciferase assays to
      demonstrate that mir-200b interacts with predicted target sites in the 3'
      untranslated region of RND3. In HeLa cells, mir-200b directly reduced the
      expression of RND3 at the mRNA and protein levels, which thereby promoted
      expression of the downstream protein cyclin D1 and increased S-phase entry. In
      conclusion, our study demonstrates a novel role for mir-200b in cell cycle
      progression and identifies RND3 as a novel mir-200b target.

PMID- 20683644
TI  - Involvement of hepatopoietin Cn in the development of human hepatocellular
      carcinoma.
AB  - Hepatopoietin Cn (HPPCn) is a novel nuclear protein with the ability to promote
      liver regeneration. In the present study, we investigated the expression profile
      of HPPCn and its functional activity in human hepatocellular carcinoma (HCC) cell
      line and tissue samples. HPPCn expression was detected in HCC cell lines and 54
      paired HCC carcinomas by immunochemical staining and Western blotting. The
      functional activity of HPPCn in cell lines was evaluated by MTT and colony
      formation assays and with nude mouse model. The correlation of HPPCn expression
      with clinicopathological characteristics of 54 HCC patients was also analyzed.
      Our results showed that HPPCn protein was prominently located within the nuclei
      of hepatocytes and the expression level was evidently increased in HepG2 and
      Bel7402 cell lines compared with L02 normal hepatocytes. HPPCn silencing by small
      interfering RNA greatly suppressed HepG2 cell proliferation and colony formation
      capacity and the inhibitory effect was also observed in a Balb/c-null mouse
      model. The silencing HPPCn expression effectively enhanced the apoptosis of HepG2
      cells. In addition, HPPCn expression was detected in 48 of 54 (89%) human HCC
      tissues in sharp contrast with the corresponding non-tumor liver tissues. HPPCn
      protein was mainly accumulated in the tumor nucleus. The elevated expression of
      HPPCn protein in tumors was significantly associated with poor tumor cellular
      differentiation and present of vascular invasion. Patients with higher HPPCn
      expression in tumors had significantly shorter overall survival (OS) of both all
      of patients and the patients at the early stage. On multivariate Cox analysis,
      elevated expression of HPPCn in tumors was found to be an independent prognostic
      factor for OS. Therefore, these data suggest that HPPCn expression might be
      involved in the development of HCC and could be served as a promising biomarker.

PMID- 20683645
TI  - Chemical space: missing pieces in cheminformatics.
AB  - Cheminformatics is at a turning point, the pharmaceutical industry benefits from
      using the various methods developed over the last twenty years, but in our
      opinion we need to see greater development of novel approaches that non-experts
      can use. This will be achieved by more collaborations between software companies,
      academics and the evolving pharmaceutical industry. We suggest that
      cheminformatics should also be looking to other industries that use high
      performance computing technologies for inspiration. We describe the needs and
      opportunities which may benefit from the development of open cheminformatics
      technologies, mobile computing, the movement of software to the cloud and
      precompetitive initiatives.

PMID- 20683647
TI  - Caterpillar chemical defense and parasitoid success: Cotesia congregata
      parasitism of Ceratomia catalpae.
AB  - Sequestration of plant compounds by herbivorous insects as a defense against
      predators is well documented; however, few studies have examined the
      effectiveness of sequestration as a defense against parasitoids. One assumption
      of the "nasty host" hypothesis is that sequestration of plant defense compounds
      is deleterious to parasitoid development. We tested this hypothesis with larvae
      of the sequestering sphingid Ceratomia catalpae, which is heavily parasitized by
      the endoparasitoid Cotesia congregata, despite sequestering high concentrations
      of the iridoid glycoside catalpol from their catalpa host plants. We collected C.
      catalpae and catalpa leaves from six populations in the Eastern US, and allowed
      any C. congregata to emerge in the lab. Leaf iridoid glycosides and caterpillar
      iridoid glycosides were quantified, and we examined associations between
      sequestered caterpillar iridoid glycosides and C. congregata performance.
      Caterpillar iridoid glycosides were not associated with C. congregata field
      parasitism or number of offspring produced. Although wasp survival was over 90%
      in all populations, there was a slight negative relationship between caterpillar
      iridoid glycosides and wasp survival. Iridoid glycosides were present in
      caterpillars at levels that are deterrent to a variety of vertebrate and
      invertebrate predators. Thus, our results support the alternative hypothesis that
      unpalatable, chemically defended hosts are "safe havens" for endoparasitoids.
      Future trials examining the importance of catalpol sequestration to potential
      natural enemies of C. congregata and C. catalpae are necessary to strengthen this
      conclusion.

PMID- 20683646
TI  - Cholesterol as a potential target for castration-resistant prostate cancer.
AB  - Advanced prostate cancer (CaP) is often treated with androgen deprivation therapy
      (ADT). Despite high initial success rates of this therapy, recurrence of the
      cancer in a castration-resistant (CRPC) form is inevitable. It has been
      demonstrated that, despite the low levels of circulating androgens resulting from
      ADT, intratumoral androgen levels remain high and androgen receptor activation
      persists. Recently, it was discovered that de novo androgen synthesis is
      occurring within the tumor cells themselves, thus providing a potential mechanism
      for the high endogenous concentrations. A common upstream precursor in this
      steroidogenic pathway is cholesterol. For many decades, the breakdown of
      cholesterol homeostasis in cancer has been the focus of research, but this was
      largely to elucidate its involvement in maintaining membrane integrity and cell
      signaling. De novo steroidogenesis has provided a new avenue for cholesterol
      research and reinforces the importance of understanding the mechanisms that lead
      to the alterations in cholesterol regulation in the progression to CRPC. The
      findings to date suggest that cholesterol homeostasis is altered to support de
      novo androgen synthesis and appear to facilitate disease progression. We further
      propose that a better understanding of the link between cholesterol and de novo
      androgen synthesis in CaP progression may provide opportunities for novel
      therapeutic intervention, namely via eliminating sources of the precursor
      cholesterol. This review summarizes the implications of cholesterol dysregulation
      in CaP and particularly in the post-ADT castration-resistant state, as well as
      the potential implementation of novel therapies targeting these cholesterol
      sources.

PMID- 20683648
TI  - Dermatophagoides pteronyssinus and Tyrophagus putrescentiae allergy in allergic
      rhinitis caused by cross-reactivity not dual-sensitization.
AB  - Tyrophagus putrescentiae and Dermatophagoides pteronyssinus are causative factors
      for the development of airway hypersensitivity. The main objective in this study
      was to identify the cross-reactive allergens between T. putrescentiae and D.
      pteronyssinus and investigate their sensitization in patients with allergic
      rhinitis. The prevalence of sensitization to mites was determined by skin prick
      tests and histamine release assays. Both immunoblot and ELISA inhibition assays
      were performed by using the recombinant allergens of T. putrescentiae and D.
      pteronyssinus. The cross-reactive allergens were identified by using IgE-binding
      inhibition analysis. The correlations of specific IgE between T. putrescentiae
      and D. pteronyssinus to group 2 and group 3 mite allergens were compared. A total
      of 117 allergic rhinitis patients, aged between 16 and 40 years old were
      recruited to be included in this study. The results showed that 70% (82/117) of
      allergic rhinitis subjects had skin test positive reactions to D. pteronyssinus
      or T. putrescentiae. Among these mite-sensitive subjects, there were 81 subjects
      (81/82) sensitive to D. pteronyssinus and 34 subjects (34/82) sensitive to T.
      putrescentiae. Among the T. putrescentiae hypersensitive subjects, 97% (33/34)
      were also sensitized to D. pteronyssinus. In the IgE-binding inhibition analysis,
      59% (13/22) subjects had IgE-binding activity of T. putrescentiae that was
      completely absorbed by D. pteronyssinus, especially components with MW at 16 kDa.
      In ELISA inhibition testing, 69% of IgE-binding was inhibited by rTyr p 2, and
      45% inhibited by rTyr p 3. The titers of IgE antibodies to rTyr p 2 and rDer p 2
      were well correlated, but not rTyr p 3 and rDer p 3. In conclusion, most T.
      putrescentiae sensitized subjects were also sensitized to D. pteronyssinus in
      young adult allergic rhinitis patients. The complete absorption of IgE binding
      activity by D. pteronyssinus indicates that T. putrescentiae hypersensitivity
      might be due to the cross-reactivity, not dual-sensitization of D. pteronyssinus
      and T. putrescentiae. The IgE-binding titers of group 2 allergens were well
      correlated and the binding activity of Tyr p 2 could be absorbed by Der p 2,
      suggesting that group 2 allergens are the major cross-reactive allergen of D.
      pteronyssinus and T. putrescentiae.

PMID- 20683649
TI  - Review of health behaviors and their correlates among young adult cancer
      survivors.
AB  - It is imperative that young adult cancer survivors address any modifiable risk
      factors, given their increased health risks. Unfortunately, few behavioral
      interventions have been developed for this population. The literature on physical
      activity, smoking, and alcohol and drug use among young adult cancer survivors
      was reviewed in order to identify the behaviors most in need of intervention, the
      most vulnerable subsets of the population, and the health behavior theories that
      might guide intervention development. This literature indicates that young adult
      cancer survivors are not meeting physical activity recommendations though smoking
      and risky drinking appear less pervasive than in the general population. Several
      demographic and medical characteristics are associated with health behaviors,
      indicating subsets of the population particularly in need of intervention. The
      literature also indicates that a few different theories and models (e.g., social
      cognitive theory, self-determination theory) might be useful in guiding the
      development of interventions for this population.

PMID- 20683650
TI  - Serosorting and the evaluation of HIV testing and counseling for HIV prevention
      in generalized epidemics.

PMID- 20683652
TI  - A non-synonymous polymorphism Thr115Met in the EpCAM gene is associated with an
      increased risk of breast cancer in Chinese population.
AB  - As a tumor-associated antigen and a surface marker of breast cancer stem cells
      (BCSCs), epithelial cell adhesion molecule (EpCAM) plays an important role in not
      only cell adhesion, morphogenesis, metastases but also carcinogenesis. A non
      synonymous C/T polymorphism (rs1126497) in exon3 of EpCAM causes a transition of
      115 amino acid from Met to Thr. Another polymorphism (A/G, rs1421) in the 3'UTR
      causes loss of has-miR-1183 binding. A multiple independent case-control analysis
      was performed to assess the association between EpCAM genotypes and breast cancer
      risk. We observed that the variant EpCAM genotype (rs1126497 CT, and TT) was
      associated with substantially increased risk of breast cancer. Genotyping a total
      of 1643 individuals with breast cancer and 1818 control subjects in Eastern and
      Southern Chinese populations showed that rs1126497 CT + TT genotype had an odd
      ratio of 1.40 (95% confidence interval, 1.16-1.57) for developing breast cancer
      compared with CC genotype. The allele T increases the risk of breast cancer in a
      dose-dependent response manner (P (trend) < 0.001). Moreover, compared to breast
      cancer patients carrying the CC genotype, the EpCAM SNP rs1126497 CT or TT
      carrier was significantly associated with early breast cancer onset (P = 0.0023).
      However, no significant difference was found in genotype frequencies at the
      rs1421 A/G site between cases and controls. These findings suggest that M115T
      polymorphism in EpCAM may be a genetic modifier for developing breast cancer.

PMID- 20683651
TI  - Structure and etiology of co-occurring internalizing and externalizing disorders
      in adolescents.
AB  - Several studies suggest that a two-factor model positing internalizing and
      externalizing factors explains the interrelationships among psychiatric
      disorders. However, it is unclear whether the covariation between internalizing
      and externalizing disorders is due to common genetic or environmental influences.
      We examined whether a model positing two latent factors, internalizing and
      externalizing, explained the interrelationships among six psychiatric disorders
      (major depressive disorder, generalized anxiety disorder, separation anxiety
      disorder, attention-deficit/hyperactivity disorder, oppositional defiant
      disorder, and conduct disorder) in adolescents, and whether there are common
      genetic and environmental influences on internalizing and externalizing latent
      factors. Multivariate behavior genetic analyses of data from 1162 twin pairs and
      426 siblings ascertained from the general population via the Colorado Center for
      Antisocial Drug Dependence (CADD) were conducted. We found support for a model
      positing two latent factors (internalizing and externalizing). These factors were
      moderately heritable and influenced by significant common genetic and nonshared
      environmental influences. These findings suggest that co-occurrence of
      internalizing and externalizing psychopathology in adolescents results from both
      genetic and environmental influences.

PMID- 20683653
TI  - Isolated and combined action of tamoxifen and metformin in wild-type, tamoxifen
      resistant, and estrogen-deprived MCF-7 cells.
AB  - Resistance to tamoxifen (TAM) and aromatase inhibitors represents a major
      drawback to the treatment of hormone-dependent breast cancer, and strategies to
      overcome this problem are urgently needed. The anti-diabetic biguanide metformin
      (MF) exerts pleiotropic effects which could enhance the effectiveness of
      available hormonal therapies. This study modeled several aspects of hormonal
      therapy in women and examined the effectiveness of MF under those conditions. For
      cell growth evaluation, wild-type (wt), TAM-resistant (TAM-R), and long-term
      estradiol-deprived (LTED) MCF-7 cells, as a model of aromatase inhibitor
      resistance, were grown in the presence or absence of TAM or MF for 5 days. For
      immunoblot analysis and aromatase activity measurements, these cells were grown
      for 48 h. Wild-type and LTED cells were equally sensitive to the growth
      inhibitory effects of TAM and MF, while TAM-R cells were less sensitive to TAM
      than to MF. Partial additive effects on cell number of TAM combined with MF were
      greatest (if compared with isolated TAM action) in TAM-R and LTED cells. In
      contrast to the decrease in PCNA values in TAM-resistant cells treated with the
      TAM and MF combination, no other changes were found in the levels of this
      proliferation marker. These findings suggested a major component of apoptosis in
      the growth inhibitory effect. This was confirmed with Western blot analysis of
      PARP and caspase 7 as well as with apoptosis ELISA assay. MF also altered
      signaling pathways. AMP-kinase was stimulated by MF approximately equally in MCF
      7, TAM-R, and LTED cells, while inhibition by biguanide of p-S6K as a downstream
      target of mTOR was strongest in TAM-R cells. Under the influence of MF,
      expression of ER-alpha was decreased in wt MCF-7 cells suggesting possible
      involvement of this compound in estrogen signaling. Metformin interacts
      additively with TAM to reduce neoplastic cells growth. The cellular context
      (including loss of sensitivity to TAM and estrogen deprivation) is of importance
      in influencing breast cancer responses to MF and to a combination of MF and TAM.

PMID- 20683654
TI  - Ecological risk assessment of water environment for Luanhe River Basin based on
      relative risk model.
AB  - The relative risk model (RRM) was applied in regional ecological risk assessments
      successfully. In this study, the RRM was developed through increasing the data of
      risk source and introducing the source-stressor-habitat exposure filter (SSH),
      the endpoint-habitat exposure filter (EH) and the stressor-endpoint effect filter
      (SE) to reflect the meaning of exposure and effect more explicit. Water
      environment which include water quality, water quantity and aquatic ecosystems
      was selected as the ecological risk assessment endpoints. The Luanhe River Basin
      located in the North China was selected as model case. The results showed that
      there were three low risk regions, one medium risk region and two high risk
      regions in the Luanhe River Basin. The results also indicated habitat destruction
      was the largest stressor with the risk scores as high as 11.87 for the Luanhe
      water environment, the second was oxygen consuming organic pollutants (9.28) and
      the third was nutrients (7.78). So these three stressors were the main
      influencing factors of the ecological pressure in the study area. Furthermore,
      animal husbandry was the biggest source with the risk scores as high as 20.38,
      the second was domestic sewage (14.00), and the third was polluting industry
      (9.96). For habitats, waters and farmland were enduring the bigger pressure and
      should be taken considerable attention. Water deterioration and ecological
      service values damaged were facing the biggest risk pressure, and secondly was
      biodiversity decreased and landscape fragmentation.

PMID- 20683655
TI  - Meeting report of the National Symposium on "Advances in Transgenic Technology
      and its Impact on the National Economy" held 23rd April 2010 at Allahabad, UP,
      India.

PMID- 20683656
TI  - Mesenteric and mediastinal lymph node infection with Linguatula serrata nymphs in
      sheep slaughtered in Kerman slaughterhouse, southeast Iran.
AB  - This research was carried out in order to detect the prevalence of nymphal stages
      of Linguatula serrata in mediastinal and mesenteric lymph nodes of sheep
      slaughtered in Kerman slaughterhouse, southeast of Iran. For this purpose,
      mesenteric and mediastinal lymph nodes of 806 sheep of different sex and age were
      examined. One hundred and thirty out of 806 (16.1%) of the sheep were found
      positive for L. serrata infection. The infection rate increased with age (P <
      0.001). Prevalence of L. serrata nymphs in males and females and different
      seasons was not significantly different (P > 0.05). Considering the results, it
      could be concluded that the prevalence of L. serrata in sheep of Kerman is high
      and plays an important role in epidemiology of linguatulosis. The zoonotic
      potential of this parasite to human health is discussed.

PMID- 20683657
TI  - Formulation of novel nano-encapsulated Newcastle disease vaccine tablets for
      vaccination of village chickens.
AB  - Formulation of nano-encapsulated vaccine tablet is a novel technique for the
      delivery of Newcastle disease (ND) vaccine to village chickens. Vaccine tablets
      were prepared using gelatin, trehalose and casein as thermostabilisers and
      binders, respectively, and each vaccine tablet contained a nominal oral dose of
      Newcastle disease virus (NDV) strain I-2 for a single chicken. These ND vaccine
      tablets maintained a titre of 10(8.5) EID(50)/0.1 mL for 90 days at ambient room
      temperatures (25-34 degrees C). When these vaccine tablets were given to village
      chickens, a single oral administration of the vaccine produced protective
      antibody response (>=3.0 log(2)) against challenge with virulent NDV. The
      findings from the present study showed that, if the vaccine tablet formulation
      technique is optimised, it will allow the delivery of the ND vaccine without
      depending on cold chains to rural areas in tropical countries.

PMID- 20683658
TI  - Frailty and muscle metabolism dysregulation in the elderly.
AB  - The frailty syndrome is increasingly recognized by geriatricians to identify
      elders at an extreme risk of adverse health outcomes. The physiological changes
      that result in frailty are complex and up to now have been extremely difficult to
      characterize due to the frequent coexistence of acute and chronic illness.
      Frailty is characterized by an decline in the functional reserve with several
      alterations in diverse physiological systems, including lower energy metabolism,
      decreased skeletal muscle mass and quality, altered hormonal and inflammatory
      functions. This altered network leads to an extreme vulnerability for disease,
      functional dependency, hospitalization and death. One of the most important core
      components of the frailty syndrome is a decreased reserve in skeletal muscle
      functioning which is clinically characterized by a loss in muscle mass and
      strength (sarcopenia), in walking performance and in endurance associated with a
      perception of exhaustion and fatigue. There are a number of physiological changes
      that occur in senescent muscle tissues that have a critical effect on body
      metabolism. The causes of sarcopenia are multi-factorial and can include disuse,
      changing hormonal function, chronic diseases, inflammation, insulin resistance,
      and nutritional deficiencies. In this review, we will explore the dysregulation
      of some biological mechanisms that may contribute to the pathophysiology of the
      frailty syndrome through age-related changes in skeletal muscle mass and
      function.

PMID- 20683659
TI  - Rates of surveillance and management of hepatocellular carcinoma in patients
      evaluated at a liver transplant center.
AB  - OBJECTIVES: The treatment of choice for HCC with cirrhosis is liver
      transplantation (LT). We assessed if patients evaluated for hepatocellular
      carcinoma are being diagnosed by surveillance, the proportion of patients meeting
      Milan criteria at diagnosis, and rates of liver transplantation. METHODS: All HCC
      cases in cirrhotic patients at Duke University Medical Center in the MELD era
      (Feb 2002-Oct 2008) were identified. Surveillance was defined as an imaging exam
      for detection of HCC in the 12 months prior to diagnosis of HCC. Logistic
      regression was used to examine predictors of LT. RESULTS: There were 319 cases
      meeting diagnostic criteria for HCC. Only 30.7% were diagnosed by surveillance
      and 43.7% met Milan criteria at diagnosis. Patients diagnosed by surveillance
      were more likely to meet Milan criteria and to receive LT (p < 0.0001 for both
      outcomes). Surveillance was associated with higher rates of LT with an OR 2.6
      (95% CI 1.2-5.7, p = 0.02). Patients managed by a hepatologist were more likely
      to be diagnosed by surveillance (65.9 vs. 19.0%, p < 0.0001). Patients meeting
      Milan criteria managed by a hepatologist were more likely to receive LT than
      those referred from other providers (26.4 vs. 8%, p = 0.009). CONCLUSIONS: A
      minority of HCC cases in cirrhotic patients were diagnosed by surveillance, and
      only 12.5% underwent LT. Patients diagnosed by surveillance were more likely to
      meet Milan criteria and to undergo LT. These findings highlight the need for
      increased identification of patients with chronic liver disease and for
      subsequent referral to hepatologists for enrollment in HCC surveillance programs.

PMID- 20683660
TI  - Immune phenotype of children with newly diagnosed and gluten-free diet-treated
      celiac disease.
AB  - BACKGROUND: Recent data suggest the involvement of both the adaptive and the
      innate immune system in celiac disease (CD). However, little is known about the
      immune phenotype of children with CD and its alteration upon dietary
      intervention. AIMS: We characterized the prevalence of major interacting members
      of the adaptive and innate immune system in peripheral blood of newly diagnosed
      children with CD and tested its alteration with the improvement of clinical signs
      after the introduction of gluten-free diet (GFD). METHODS: Peripheral blood was
      taken from ten children with biopsy-proven CD at the time of diagnosis and after
      the resolution of clinical symptoms following GFD. As controls, 15 children with
      functional abdominal pain were enrolled. The prevalence of the cells of adaptive
      and innate immunity was measured with labeled antibodies against surface markers
      and intracellular FoxP3 using a flow cytometer. RESULTS: Patients with CD were
      found to have lower T helper, Th1 and natural killer (NK), NKT and invariant NKT
      cell prevalence and with higher prevalence of activated CD4(+) cells, myeloid
      dendritic cells (DC) and Toll-like receptor (TLR) 2 and TLR-4 positive DCs and
      monocytes compared to controls. After resolution of symptoms on GFD, the majority
      of these changes normalized, although the prevalence of NK and NKT cell, DC and
      TLR-2 expressing DCs and monocytes remained abnormal. CONCLUSIONS: The immune
      phenotype in childhood CD indicates the implication of both adaptive and innate
      immune system. The normalization of immune abnormalities occurs on GFD, but the
      kinetics of this process probably differs among different cell types.

PMID- 20683661
TI  - The effect of exopolysaccharide-producing probiotic strains on gut oxidative
      damage in experimental colitis.
AB  - BACKGROUND: Oxidative stress plays a role in disease initiation and progression
      in inflammatory bowel disease (IBD) and manipulation of this pathway may
      attenuate disease progress. In this study, the effect of exopolysaccharide (EPS)
      producing probiotic bacteria on gut oxidative damage was evaluated in a rat model
      of experimental colitis. METHODS: Colitis was induced by intracolonic
      administration of acetic acid. Rats were treated daily with two probiotic
      strains, L. delbrueckii subsp. bulgaricus B3 strain (EPS of 211 mg/l; high-EPS
      group) or L. delbrueckii subsp. bulgaricus A13 strain (EPS of 27 mg/l; low-EPS
      group), which were given directly into the stomach. Non-colitis-fed control and
      preventative groups were only treated with the high-EPS producing strain.
      Antioxidant enzyme activities (superoxide dismutase, catalase, total glutathione,
      reduced glutathione, glutathione disulfide) and lipid peroxidation were measured
      in colonic tissue samples after a treatment period of 7 days. RESULTS:
      Significant oxidative damage was associated with a higher level of
      malondialdehyde (MDA) activity and reduced antioxidant enzyme activities in the
      colitis model group. All antioxidant enzyme activities were higher in both
      probiotic-treated groups compared with those of the colitis model group (P <
      0.001). Lipid peroxidation was significantly ameliorated in both probiotic
      groups. The improvement of oxidative stress parameters was significantly more in
      the high-EPS group than in the low-EPS group (P < 0.001). CONCLUSIONS: EPS
      producing probiotic bacteria significantly attenuate oxidative stress in
      experimental colitis. Increased EPS production gives rise to a better probiotic
      function. These results suggest that EPS molecules could revaluate probiotic
      strains and exert their beneficial effects on the host and this may have a
      therapeutic potential.

PMID- 20683662
TI  - Exfoliative rejection in intestinal transplantation.

PMID- 20683663
TI  - Pancreatic cancer cells resistant to chemoradiotherapy rich in "stem-cell-like"
      tumor cells.
AB  - BACKGROUND: Tumor resistance to chemoradiation therapy is partly attributed to
      the presence of apoptosis-resistant cancer stem cells (CSCs). Chemoradiation
      therapy can enrich CSCs by killing apoptosis-susceptible cancer cells. AIM: Our
      preliminary study showed chemoradiation-resistant pancreatic cancer cells to have
      some CSC characteristics, and to undergo epithelial-mesenchymal transition (EMT);
      we aimed to verify that study's implication that chemoradiation-resistant
      subpopulations are enriched with "stem-cell-like" tumor cells, which may be
      linked to EMT. METHODS: Four pancreatic cancer cell lines were cultured in
      gemcitabine with synchronous radiotherapy to obtain resistant subpopulations.
      Morphological changes were observed under microscope; migration and invasiveness
      were assessed by Transwell tests. Protein expression was determined by
      immunoblotting. Pancreatic CSC markers were studied using fluorescence-activated
      cell sorting analyses. Colony-formation tests, tumor sphere formation assays, and
      tumor xenografts in BALB/C nude mice were used to evaluate "stemness" in
      resistant cells. RESULTS: Resistant cells expressed more antiapoptotic protein
      Bcl-2, apoptosis-inhibitory protein survivin, and stem cell markers Oct4, ABCG2,
      CD24, and CD133, were more tumorigenic in vitro and in vivo, and showed
      phenotypic and molecular changes consistent with EMT, including upregulation of
      vimentin and downregulation of E-cadherin. They were also more invasive and
      migratory. CONCLUSIONS: We found chemoradiation-resistant pancreatic cancer cells
      to be similar to CSCs and to undergo EMT, suggesting that chemoradiation
      resistance-induced EMT is linked to CSC generation.

PMID- 20683664
TI  - The prevalence of evidence-based drug use prevention curricula in U.S. middle
      schools in 2008.
AB  - The No Child Left Behind Act mandates the implementation of evidence-based drug
      prevention curricula in the nation's schools. The purpose of this paper is to
      estimate changes in the prevalence of such curricula from 2005 to 2008. We
      surveyed school staff in a nationally representative sample of schools with
      middle school grades. Using a web-based approach to data collection that we
      supplemented by telephone calls, we secured data from 1892 schools for a response
      rate of 78.2%. We estimate that the prevalence of evidence-based drug prevention
      curricula rose from 42.6% in 2005 to 46.9% in 2008, and that the prevalence of
      schools that used these curricula most frequently increased from 22.7% to 25.9%
      over this period. In addition, the proportion of schools using locally developed
      curricula also rose, from 17.6% to 28.1%. This study suggests the success of
      efforts by the Office of Safe and Drug-Free Schools to increase the prevalence of
      evidence-based curricula, as well as the need to continue to track the prevalence
      of these curricula in response to any reductions in the Office's fiscal support
      for evidence-based drug prevention curricula in the nation's schools.

PMID- 20683665
TI  - In vitro and in vivo characterisation of a novel c-FLIP-targeted antisense
      phosphorothioate oligonucleotide.
AB  - Previous studies have suggested that the caspase 8 inhibitor FLIP is a promising
      anti-cancer therapeutic target. In this study, we characterised a novel FLIP
      targeted antisense phosphorothioate oligonucleotide (AS PTO). FLIP AS and control
      PTOs were assessed in vitro in transient transfection experiments and in vivo
      using xenograft models in Balb/c nude mice. FLIP expression was assessed by QPCR
      and Western. Apoptosis induction was determined by flow cytometry and Western. Of
      5 sequences generated, one potently down-regulated FLIP. AS PTO-mediated down
      regulation of FLIP resulted in caspase 8 activation and apoptosis induction in
      non-small cell lung (NSCLC) cells but not in normal lung cells. Similar results
      were observed in colorectal and prostate cancer cells. Furthermore, the FLIP AS
      PTO sensitized cancer cells but not normal lung cells to apoptosis induced by
      rTRAIL. Moreover, the FLIP AS PTO enhanced chemotherapy-induced apoptosis in
      NSCLC cells. Importantly, compared to a control non-targeted PTO, intra
      peritoneal delivery of FLIP AS PTO inhibited the growth of NSCLC xenografts and
      enhanced the in vivo antitumour effects of cisplatin. We have identified a novel
      FLIP-targeted AS PTO that has in vitro and in vivo activity and which therefore
      has potential for further pre-clinical development.

PMID- 20683666
TI  - JNK-mediated transcriptional upregulation of RhoB is critical for apoptosis of
      HCT-116 colon cancer cells by a novel diarylsulfonylurea derivative.
AB  - Diarylsulfonylureas are potent antitumor agents that have been tested in clinical
      trials. However, detailed mechanisms of their apoptotic activity remain unclear.
      Here, we report a new diarylsulfonylurea derivative, LB2A, that upregulates RhoB,
      thereby inducing potent apoptosis in HCT-116 human colon cancer cells
      independently of p53 status. LB2A decreased procaspase-3, increased phospho-JNK,
      and cleaved PARP, leading to apoptosis of HCT-116 cells. Prior treatment of HCT
      116 cells with the JNK inhibitor SP600125 and the RNA synthesis inhibitor DRB
      blocked apoptosis, implying that JNK activation and mRNA production are important
      for apoptosis by LB2A. Western blotting, RT-PCR, and RhoB-promoter luciferase
      reporter assays revealed that LB2A increased RhoB via JNK-mediated
      transcriptional activation. LB2A decreased HDAC1 and increased acetyl-H3, both of
      which activate the RhoB promoter and were blocked by SP600125. Ectopic expression
      of RhoB induced apoptosis of HCT-116 cells, suggesting that RhoB is critical for
      the anti-cancer activity of LB2A in human colon cancer cells. LB2A also exhibited
      potent tumor growth inhibition of HCT-116 cells in vivo using a mouse xenograft
      assay. Taken together, these results show that LB2A induces apoptosis of HCT-116
      cells via JNK-mediated transcriptional upregulation of RhoB and may therefore
      provide a potential therapy for human colon cancer.

PMID- 20683667
TI  - Clearance of dying cells and systemic lupus erythematosus: the role of C1q and
      the complement system.
AB  - Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease of unknown
      etiology characterized by the presence of pathogenic high-titer autoantibodies to
      a diverse group of autoantigens. In 88% of patients, autoantibodies are present
      an average of 3.3 years before diagnosis. Antinuclear, anti-Ro, anti-La, and anti
      phospholipid antibodies appear first, followed by anti-DNA, anti-Smith and anti
      ribonucleoprotein. These autoantibodies have features of an antigen-driven, T
      cell-dependent immune response. Once present, the course of SLE is characterized
      by disease flares and autoimmune dysregulation. Programmed cell death (PCD), an
      essential developmental and homeostatic mechanism, is the preferred physiological
      death processes for cells as well as an important immune response regulator.
      Appropriate clearance of apoptotic material completes the PCD process, and is
      essential for regulating of inflammation and maintaining self-tolerance. Early
      complement proteins are important in protecting humans against the development of
      SLE and the protective role of C1q and complement in SLE is mainly related to
      their role in clearance of dying cells. However, the complement system is also an
      important ingredient in inflammation, which mediates SLE pathogenesis. Thus, the
      question remains whether complement factors have either a protective or a
      destructive role, or a combination of both.

PMID- 20683668
TI  - Focal splenic lesions in type I Gaucher disease are associated with poor platelet
      and splenic response to macrophage-targeted enzyme replacement therapy.
AB  - Focal splenic lesions (FSL) occur in Gaucher disease type I (GD1), but their
      clinical significance is not known. Previous studies estimated the prevalence of
      FSL at 4% (pediatric) to 33% (adult) of GD1 patients and reported an association
      with splenomegaly. We tested the hypothesis that the presence of FSL is
      associated with suboptimal response to macrophage-directed enzyme replacement
      therapy (ERT). Additionally we investigated whether FSL were associated with
      other phenotypic features of GD1. The splenic parenchyma was assessed by MRI
      performed for routine evaluation of GD1 in 239 consecutive GD1 patients with
      intact spleens. The prevalence of FSL was 18.4% (44/239). Following a mean of 3.5
      years of ERT, platelet response was inferior among patients with FSL (80,700 +/-
      9,600 to 90,100 +/- 7,200/mm(3) , P = 0.2) compared to patients without FSL in
      whom there was a robust platelet response: 108,600 +/- 5,670 to 150,200 +/-
      6,710/mm(3), P < 0.001. Compared to patients without FSL, patients harboring FSL
      had worse thrombocytopenia (platelet count: 83,700 +/- 8,800 vs. 112,100 +/-
      4,200/mm(3), P = 0.004), greater frequency of pre-ERT splenomegaly, and greater
      post-ERT splenomegaly (8.5 +/- 0.77 vs. 4.8 +/- 0.25* normal, P < 0.001).
      Additionally, the prevalence of osteonecrosis was higher among patients with FSL
      compared to patients without FSL (38 vs. 20.7%, P = 0.026). FSL appear to be a
      determinant of response to ERT, suggesting studies comparing relative efficacy of
      newly emerging therapies for GD1 should adjust for this factor. Moreover,
      occurrences of FSL coincide with more severe manifestations of GD1 such as
      avascular osteonecrosis.

PMID- 20683669
TI  - Past, present and future of newborn screening in Chile.
AB  - The history of the Newborn Screening Program in Chile begins in 1984, when a
      pilot plan was developed that demonstrated the feasibility of its implementation.
      In 1992, the Ministry of Health started a national newborn screening program for
      phenylketonuria (PKU) and congenital hypothyroidism (CH), and in 1998, this was
      extended to the entire country. Throughout this period, a total of 2,478,123
      newborns (NB) have been analyzed, obtaining initial coverage of 48.8%, which was
      later increased to 87.7%, and at present it is at 98.7% of all NB of our country.
      During this period, 131 cases with PKU have been diagnosed, resulting in an
      incidence of 1:18,916 NB, an average age of diagnosis of 18 +/- 10.2 days and
      average phenylalanine level of 19,9 +/- 8.8 mg/dl. In relation to CH, 783 cases
      have been confirmed, arriving at an incidence of 1:3,163 NB, with average age of
      diagnosis of 12.5 +/- 6.9 days. Due to the good results of the program, the
      government is evaluating the initiation of an extended pilot program, to
      introduce other pathologies.

PMID- 20683670
TI  - Detection of hepatic metastases using dual-time-point FDG PET/CT scans in
      patients with colorectal cancer.
AB  - PURPOSE: The purpose of this study was to determine the most useful parameter of
      dual-time-point 2-deoxy-2-[18F]fluoro-D: -glucose positron emission
      tomography/computed tomography (PET/CT) for detection of hepatic metastases in
      patients with colorectal cancer. PROCEDURES: Thirty-nine patients had undergone a
      dual-time-point PET/CT scan and a subsequent histopathological confirmation for a
      workup of hepatic metastases. Detection rates were compared for visual analysis
      score, standardized uptake value (SUV), tumor-to-liver uptake ratio (TLR), and
      percent changes of the SUV and TLR. RESULTS: Of 91 liver lesions, 86 lesions were
      confirmed as metastases. The SUV and TLR of metastatic lesions on the delayed
      images were higher than those on the first scan (p < 0.001). The signal-to-noise
      ratio of the delayed PET scan was higher than that of the first scan (p <
      0.0001). The TLR and SUV of the delayed scan showed the highest detection rates
      of 92% and 88%, whereas percent changes of SUV and TLR showed the lowest
      detection rates (51%, 67%). Visual analysis detected 87% on the delayed scan and
      77% on the first scan. CONCLUSIONS: A delayed scan is more favorable for the
      detection of hepatic metastases of colorectal cancer, and the TLR on the delayed
      scan was the most useful parameter.

PMID- 20683671
TI  - Biosensors of DsRed as FRET partner with CFP or GFP for quantitatively imaging
      induced activation of Rac, Cdc42 in living cells.
AB  - PURPOSE: The suboptimal features of the spectral properties of the leading
      fluorescence resonance energy transfer (FRET) pair, cyan fluorescent protein
      (CFP)/yellow fluorescent protein (YFP), limit the full promise of FRET imaging.
      To overcome the drawbacks, we developed FRET-based, intra-molecular biosensors
      consisting of CFP/discomona sp red fluorescent protein (DsRed) or green
      fluorescent protein (GFP)/DsRed as donor/acceptor fluorophores. PROCEDURES: The
      biosensors were expressed in NIH3T3 cells. In vitro fluorescence spectroscopy and
      Rho GTPase activation assays were used to confirm that Rac1 or Cdc42 was
      activated in serum-starved cells following stimulation with insulin or
      bradykinin. The transient changes of the amount, location, and translocation of
      activated Rac1 or Cdc42 in living cells were tracked with confocal imaging.
      RESULTS: The increase of FRET efficiency was achieved in the cells expressing the
      biosensors and was proportional to the levels of activated Rac1 or Cdc42. The
      localized, transitional, and transient FRET signals were directly and
      quantitatively imaged with high spatial and temporal resolution. The biosensors
      were used to analyze and judge the GEF or GAP activities of putative regulatory
      proteins for Rac1 or Cdc42. CONCLUSION: DsRed is a more suitable acceptor in FRET
      pair with CFP than with GFP in terms of the spectral overlap between the donor
      and acceptor. The approach can also be applied to many other types of protein
      behavior in living cells.

PMID- 20683672
TI  - [Questionnaire surveying nephrologists on drug dose adjustment in patients with
      impaired kidney function].
AB  - OBJECTIVE: Our intention was to assess knowledge and requirements related to drug
      dose adjustment in patients with impaired kidney function. METHOD: In 2005, we
      sent a questionnaire containing 22 questions to nephrologists in Germany and
      Austria. With 77 responses, the study was not representative. However, it was
      probably of importance for the target group of practising physicians and
      potential users of a future drug information system. RESULTS: Only 28% of the
      responding colleagues use the package inserts; these are obviously not considered
      to be an obligatory guideline for dose adjustment. The most common dosing
      problems (p < 0.05) were associated with anti-infective (48%) and anti-cancer
      drugs (25%). The greatest problems with dosing were encountered within intensive
      care units (29%). The risk of excessive dosing is estimated significantly more
      serious than the risk of underdosing (51% vs. 23%, p = 0.02). There was support
      for the statement that for cephalosporin antibiotics the trough levels are more
      important than peak levels (58% vs. 27%, p < 0.01). However, only 8% knew that in
      patients with impaired kidney function, trough concentrations of aminoglycosides
      and vancomycin need to be higher than in patients with normal kidney function for
      adequate peak levels to be obtained. Forty-five percent of respondents
      erroneously presumed that ceftriaxone must be adjusted to the kidney function.
      Half of the respondents were incorrect in assuming that ceftriaxone or
      moxifloxacin would be removed by dialysis. CONCLUSIONS: We see the need for more
      knowledge-based information on drug dosing in patients with kidney impairment and
      those in the intensive care unit. The risk to life posed by underdosage might be
      underestimated, especially for anti-infective drugs.

PMID- 20683673
TI  - [Sedation and analgesia in intensive care: physiology and application].
AB  - Many therapeutic and diagnostic procedures in intensive care medicine are
      perceived as painful by most patients. As a consequence analgesia and sedation
      represent two of the main pillars in the treatment of the critically ill.
      Adaptation to the individual needs of the patients poses one of the biggest
      challenges that we are confronted with. Both morbidity and mortality can be
      positively influenced by adequate treatment. In the first part of this review we
      will discuss the physiology of sleep patterns and pain. Furthermore modes of
      action and side effects of the most common anesthetics and analgetics will be
      presented. Finally, the last part of the manuscript deals with the practical
      application of these therapeutics and their monitoring in intensive care
      medicine.

PMID- 20683674
TI  - An evaluation of Australian pharmacist's attitudes on expanding their prescribing
      role.
AB  - OBJECTIVES: To evaluate the views of Australian pharmacists on expanded
      pharmacist prescribing roles and identify important drivers and barriers to its
      implementation. Setting Pharmacists in Australia. METHOD: Data were collected
      using a self-administered questionnaire distributed nationally to a random sample
      of pharmacists either directly, or in the case of one state, via community
      pharmacies. One-way ANOVA and kappa(2) testing were used to identify significant
      associations. Factor analysis was conducted to pool variables and the derived
      factors were subjected to regression analysis. MAIN OUTCOME MEASURES: Perceptions
      of Australian pharmacists on expanded prescribing and the relationships between
      variables derived. RESULTS: A total of 2592 questionnaires were distributed and a
      response rate of 40.4% was achieved (n = 1049). Of the respondents 83.9% strongly
      agreed/agreed to an expanded prescribing role for pharmacists and 97.1% reported
      they would need further training. Of the respondents 896 agreed that pharmacists
      should engage in supplementary, independent prescribing or both. Of these 69.1%
      preferred only supplementary prescribing, 3.3% independent prescribing and 27.4%
      both models. Both models were found to be positive predictors of expanding
      pharmaceutical services through prescribing (P < 0.001) with supplementary
      prescribing showing a stronger association (beta = 0.52 vs. beta = 0.18).
      Pharmacists' opinion based on their current perceptions of their clients was an
      important predictor in expanding pharmaceutical services through prescribing (P =
      0.005). Inadequate training in patient assessment, diagnosis and monitoring were
      the strongest barriers to expanded pharmacist prescribing (P < 0.001).
      CONCLUSIONS: The majority of Australian pharmacists supported an expanded
      pharmacist prescribing role. Support for supplementary was stronger than
      independent prescribing. Pharmacists acknowledged that they would need further
      training to perform such roles.

PMID- 20683675
TI  - Estimation of ligament loading and anterior tibial translation in healthy and ACL
      deficient knees during gait and the influence of increasing tibial slope using
      EMG-driven approach.
AB  - The purpose of this study was to develop a biomechanical model to estimate
      anterior tibial translation (ATT), anterior shear forces, and ligament loading in
      the healthy and anterior cruciate ligament (ACL)-deficient knee joint during
      gait. This model used electromyography (EMG), joint position, and force plate
      data as inputs to calculate ligament loading during stance phase. First, an EMG
      driven model was used to calculate forces for the major muscles crossing the knee
      joint. The calculated muscle forces were used as inputs to a knee model that
      incorporated a knee-ligament model in order to solve for ATT and ligament forces.
      The model took advantage of using EMGs as inputs, and could account for the
      abnormal muscle activation patterns of ACL-deficient gait. We validated our model
      by comparing the calculated results with previous in vitro, in vivo, and
      numerical studies of healthy and ACL-deficient knees, and this gave us confidence
      on the accuracy of our model calculations. Our model predicted that ATT increased
      throughout stance phase for the ACL-deficient knee compared with the healthy
      knee. The medial collateral ligament functioned as the main passive restraint to
      anterior shear force in the ACL-deficient knee. Although strong co-contraction of
      knee flexors was found to help restrain ATT in the ACL-deficient knee, it did not
      counteract the effect of ACL rupture. Posterior inclination angle of the tibial
      plateau was found to be a crucial parameter in determining knee mechanics, and
      increasing the tibial slope inclination in our model would increase the resulting
      ATT and ligament forces in both healthy and ACL-deficient knees.

PMID- 20683676
TI  - Non-invasive diagnosis of risk in dengue patients using bioelectrical impedance
      analysis and artificial neural network.
AB  - This paper presents a new approach to diagnose and classify early risk in dengue
      patients using bioelectrical impedance analysis (BIA) and artificial neural
      network (ANN). A total of 223 healthy subjects and 207 hospitalized dengue
      patients were prospectively studied. The dengue risk severity criteria was
      determined and grouped based on three blood investigations, namely, platelet
      (PLT) count (less than or equal to 30,000 cells per mm(3)), hematocrit (HCT)
      (increase by more than or equal to 20%), and either aspartate aminotransferase
      (AST) level (raised by fivefold the normal upper limit) or alanine
      aminotransferase (ALT) level (raised by fivefold the normal upper limit). The
      dengue patients were classified according to their risk groups and the
      corresponding BIA parameters were subsequently obtained and quantified. Four
      parameters were used for training and testing the ANN which are day of fever,
      reactance, gender, and risk group's quantification. Day of fever was defined as
      the day of fever subsided, i.e., when the body temperature fell below 37.5
      degrees C. The blood investigation and the BIA data were taken for 5 days. The
      ANN was trained via the steepest descent back propagation with momentum algorithm
      using the log-sigmoid transfer function while the sum-squared error was used as
      the network's performance indicator. The best ANN architecture of 3-6-1 (3
      inputs, 6 neurons in the hidden layer, and 1 output), learning rate of 0.1,
      momentum constant of 0.2, and iteration rate of 20,000 was pruned using a weight
      eliminating method. Eliminating a weight of 0.05 enhances the dengue's prediction
      risk classification accuracy of 95.88% for high risk and 96.83% for low risk
      groups. As a result, the system is able to classify and diagnose the risk in the
      dengue patients with an overall prediction accuracy of 96.27%.

PMID- 20683677
TI  - Leptin regulates MMP-2, TIMP-1 and collagen synthesis via p38 MAPK in HL-1 murine
      cardiomyocytes.
AB  - A clear association between obesity and heart failure exists and a significant
      role for leptin, the product of the obese gene, has been suggested. One aspect of
      myocardial remodeling which characterizes heart failure is a disruption in the
      balance of extracellular matrix synthesis and degradation. Here we investigated
      the effects of leptin on matrix metalloproteinase (MMP) activity, tissue
      inhibitor of metalloproteinase (TIMP) expression, as well as collagen synthesis
      in HL-1 cardiac muscle cells. Gelatin zymographic analysis of MMP activity in
      conditioned media showed that leptin enhanced MMP-2 activity in a dose- and time
      dependent manner. Leptin is known to stimulate phosphorylation of p38 MAPK in
      cardiac cells and utilization of the p38 MAPK inhibitor, SB203580, demonstrated
      that this kinase also plays a role in regulating several extracellular matrix
      components, such that inhibition of p38 MAPK signaling prevented the leptin
      induced increase in MMP-2 activation. We also observed that leptin enhanced
      collagen synthesis determined by both proline incorporation and picrosirius red
      staining of conditioned media. Pro-collagen type-I and pro-collagen type-III
      expression, measured by real-time PCR and Western blotting were also increased by
      leptin, effects which were again attenuated by SB203580. In summary, these
      results demonstrate the potential for leptin to play a role in mediating
      myocardial ECM remodeling and that the p38 MAPK pathway plays an important role
      in mediating these effects.

PMID- 20683678
TI  - Sorafenib and radiation therapy for the treatment of advanced hepatocellular
      carcinoma.
AB  - INTRODUCTION: Treatment options for advanced hepatocellular cancer (HCC) are
      limited. Sorafenib, an orally active multi-kinase inhibitor, is the only systemic
      agent with a survival benefit in randomized studies. However, the gain in
      survival is modest and new treatment strategies are needed. CLINICAL CASES: We
      report two cases of advanced HCC treated with a combination of sorafenib and
      radiation therapy. Impressive and sustained clinical and radiological responses
      were seen. Treatment was well-tolerated in both cases with no unexpected
      toxicities reported. DISCUSSION: There is sound rationale for the combination of
      sorafenib and radiation therapy for treatment of HCC. These two cases suggest
      both feasibility and efficacy of this combination, in selected patients.
      Prospective studies addressing this combination are ongoing.

PMID- 20683679
TI  - Inflammatory cytokine induced regulation of superoxide dismutase 3 expression by
      human mesenchymal stem cells.
AB  - Increasing evidence suggests that bone marrow derived-mesenchymal stem cells
      (MSCs) have neuroprotective properties and a major mechanism of action is through
      their capacity to secrete a diverse range of potentially neurotrophic or anti
      oxidant factors. The recent discovery that MSCs secrete superoxide dismutase 3
      (SOD3) may help explain studies in which MSCs have a direct anti-oxidant activity
      that is conducive to neuroprotection in both in vivo and in vitro. SOD3
      attenuates tissue damage and reduces inflammation and may confer neuroprotective
      effects against nitric oxide-mediated stress to cerebellar neurons; but, its role
      in relation to central nervous system inflammation and neurodegeneration has not
      been extensively investigated. Here we have performed a series of experiments
      showing that SOD3 secretion by human bone marrow-derived MSCs is regulated
      synergistically by the inflammatory cytokines TNF-alpha and IFN-gamma, rather
      than through direct exposure to reactive oxygen species. Furthermore, we have
      shown SOD3 secretion by MSCs is increased by activated microglial cells. We have
      also shown that MSCs and recombinant SOD are able to increase both neuronal and
      axonal survival in vitro against nitric oxide or microglial induced damage, with
      an increased MSC-induced neuroprotective effect evident in the presence of
      inflammatory cytokines TNF-alpha and IFN-gamma. We have shown MSCs are able to
      convey these neuroprotective effects through secretion of soluble factors alone
      and furthermore demonstrated that SOD3 secretion by MSCs is, at least, partially
      responsible for this phenomenon. SOD3 secretion by MSCs maybe of relevance to
      treatment strategies for inflammatory disease of the central nervous system.

PMID- 20683680
TI  - The effect of an electronic control device on muscle injury as determined by
      creatine kinase enzyme.
AB  - The medical literature on the effect of electronic control devices (ECD) on
      muscle injury is sparse. In this paper, we examine pooled data from five human
      studies that used creatine kinase (CK) as a marker for muscle injury. CK was
      measured in five separate studies involving four TASER ECDs with different
      exposure durations and number of circuits or contact points. Device type,
      exposure duration, number of circuits or contact points, and CK values at
      baseline and 24 h after exposure were pooled from these previous studies. Data
      were analyzed to determine the correlation of CK to duration of exposure, number
      of contact points, and distance between the probes. The pooled results contained
      163 subjects. Seven were withdrawn due to incomplete data, leaving 156 subjects
      for analysis (median age 36, range 19-67, 93.6% male). 121 (77.6%) subjects had 2
      contacts points, 10 (6.4%) had 3 contact points, 18 (11.5%) had 4 contact points,
      and 7 (4.5%) had 6 contact points. 81 (51.9%) subjects had a 5-s exposure, 64
      (41.0%) a 10-s exposure, and, 11 (7.1%) a 30-s exposure. Median baseline CK (145
      U/l, IQR 104-217, range 12-1956) did not differ between groups (P = 0.213 for
      number of contact points, 0.124 for duration). For the number of contacts, the
      median change in CK for 2 points of contact was 32 (IQR -1 to 1513, range -205 to
      1821), for 3 was 1456 (IQR 634-1868, range 101-25452), for 4 was 887 (IQR 285
      7481, range -1054 to 7481), and for 6 was 846 (IQR 57-1149, range -8 to 2309), (P
      < 0.001). For duration, the median change in CK for 5 s was 26.5 (IQR -8 to 109,
      range -1054 to 2309), for 10 s was 303 (IQR 34.5-1073, range -205 to 25452), and
      for 30 s was 47 (IQR 23-82, range -140 to 364), (P < 0.001). There was a
      relationship between the number of points of contact and the change in CK (P <
      0.001) but not a relationship between the duration and the change in CK (P =
      0.496). The median spread between the probe pairs for our pooled data was 40 cm,
      with a range from 18 to 70 cm (n = 76). The correlation between the change in CK
      and spread between the probe pairs was 0.16 at baseline (P = 0.18), and 0.24 at
      24 h (P = 0.04) by Spearman's rank correlation. ECD exposure can cause a modest
      increase in CK. Although we cannot draw conclusions about the individual devices
      included in this analysis, our findings indicated that multiple contact points or
      exposures may result in a larger increase in CK, but the duration of the exposure
      does not appear to have a significant effect on CK. There is a correlation
      between the distance between the probes and the change in CK.

PMID- 20683681
TI  - Computer-assisted therapy in psychiatry: be brave-it's a new world.
AB  - The capacity to deliver some forms of behavioral treatment via computers may
      prove to be a small revolution in the delivery of mental health care. Although
      early research on the efficacy of these approaches has yielded mixed results,
      this new strategy offers tremendous potential to provide empirically supported
      therapies to many individuals who would never access psychiatric care, to extend
      the time and expertise of clinicians, and to offer improved care and monitoring.
      However, the great promise of computer-assisted therapies may be diminished if
      their benefits are overstated or if they are broadly released or disseminated
      before being carefully evaluated using the same methodologic standards that are
      requirements for evaluating clinician-delivered therapies. In this article, we
      review the current status of empiric support for computer-assisted therapies,
      advocating for enhanced rigor to identify those that are most effective, as well
      as the need to more thoroughly assess possible adverse effects, recognizing that
      even a modestly effective computer-assisted intervention could have enormous
      impact.

PMID- 20683682
TI  - Intestinal stem cells.
AB  - Self-renewal in the intestinal epithelia is fueled by a population of
      undifferentiated intestinal stem cells (ISCs) that give rise to daughter or
      progenitor cells, which can subsequently differentiate into the mature cell types
      required for normal gut function. The cellular signals that regulate self-renewal
      are poorly understood and the factors that mediate the transition from a stem
      cell to a progenitor cell in the gut are unknown. Recent studies have suggested
      that ISCs are located either at the crypt base interspersed between the Paneth
      cells (eg, Lgr-5+ve cells) or at or near position 4 within the intestinal crypt
      (eg, DCAMKL-1 or Bmi-1+ve cells). This raises the possibility that distinct stem
      cell regions exist in the crypts and that ISC's state of activation will
      determine how the self-renewal is regulated in the intestinal tract.

PMID- 20683683
TI  - Molecular- and flow cytometry-based diagnosis of primary immunodeficiency
      disorders.
AB  - Primary immunodeficiencies are an expanding group of genetic disorders resulting
      in recurrent and/or severe infections, autoimmunity, or autoinflammation. The
      laboratory plays a critical role in the diagnosis of these conditions given their
      frequently overlapping signs and symptoms. We discuss here advances in flow
      cytometry and molecular techniques applied to the study of primary
      immunodeficiencies.

PMID- 20683684
TI  - Remarkable polymorphism of HLA-B27: an ongoing saga.
AB  - Histocompatibility antigen HLA-B27 is a normal gene that is distributed worldwide
      with variable prevalence and shows a remarkable association with ankylosing
      spondylitis and related spondyloarthropathies. The precise biological explanation
      for this remarkable association remains elusive. HLA-B27 represents a family of
      closely related proteins encoded by an ever-increasing number of alleles; there
      are 75 alleles of HLA-B27 known thus far, based on nucleotide sequence
      differences, but at the translated protein level, there are 62 known subtypes of
      HLA-B27. Not all subtypes are disease associated. Moreover, existence of a
      possible hierarchical ranking among some of the subtypes for their disease
      association has been observed.

PMID- 20683685
TI  - Late-onset differentiation syndrome in a child with acute promyelocytic leukemia.

PMID- 20683686
TI  - A novel WASP gene mutation in a Chinese boy with Wiskott-Aldrich syndrome.
AB  - Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disorder characterized by
      thrombocytopenia, small platelets, eczema, increased susceptibility to infection,
      and immunodeficiency. Mutations of the Wiskott-Aldrich syndrome protein (WASP)
      gene are responsible for this severe congenital disease. In this study, we report
      on a 2-year-old Chinese boy who presented with classic clinical WAS
      manifestations. By direct sequencing of cDNA and genomic DNA of the patient, we
      identified a novel mutation: the first nucleotide in exon 8 (G) had been deleted
      (769delG). This mutation results in two kinds of aberrant mRNA with abnormal
      splicing and causes frameshift and a stop codon at amino acid 260. Western
      blotting demonstrated a 28-kDa truncated WAS protein. A maternal study revealed
      that his mother had a heterozygous genotype, but showed normal WASP expression.

PMID- 20683687
TI  - Development and characterization of mucoadhesive in situ nasal gel of midazolam
      prepared with Ficus carica mucilage.
AB  - The objective of the present study was to prepare mucoadhesive in situ nasal gels
      with mucilage isolated from fig fruits (Ficus carica, family: Moraceae)
      containing midazolam hydrochloride. Nasal gels of midazolam were prepared using
      three different concentrations (0.5%, 1.0% and 1.5% w/v) of F. carica mucilage
      (FCM) and synthetic polymers (hydroxypropylmethyl cellulose and Carbopol 934).
      Evaluation of FCM showed that it was as safe as the synthetic polymers for nasal
      administration. In situ gels were prepared with mixture Pluronic F127 and
      mucoadhesive agents. Evaluation of the prepared gels was carried out, including
      determination of viscosity, texture profile analysis and mucoadhesive strength.
      In vitro drug permeation study was conducted with the gels prepared with and
      without permeation enhancer (0.5% w/v sodium taurocholate) using excised goat
      nasal mucosa. In vitro permeation profiles were evaluated, and histological study
      of nasal mucosae before and after permeation study was also conducted to
      determine histological change, if any. In vivo experiments conducted in rabbits
      further confirmed that in situ nasal gels provided better bioavailability of
      midazolam than the gels prepared from synthetic mucoadhesive polymers. It was
      observed that the nasal gel containing 0.5% FCM and 0.5% sodium taurocholate
      exhibited appropriate rheological, mechanical and mucoadhesive properties and
      showed better drug release profiles. Moreover, this formulation produced no
      damage to the nasal mucosa that was used for the permeation study, and absolute
      bioavailability was also higher compared to gels prepared from synthetic
      polymers.

PMID- 20683688
TI  - Perioperative complications of simultaneous versus staged unicompartmental knee
      arthroplasty.
AB  - BACKGROUND: The complication risk of staged versus simultaneous total knee
      arthroplasty continues to be debated in the literature. Previous reports suggest
      unicompartmental knee arthroplasty provides a more rapid functional recovery than
      total knee arthroplasty. However, little data exist on whether simultaneous
      unicompartmental knee arthroplasty can be performed without increasing the
      perioperative risk compared with staged unicompartmental knee arthroplasty.
      QUESTIONS/PURPOSES: We therefore asked if there is an increased risk of
      perioperative complications with bilateral simultaneous unicompartmental knee
      arthroplasty. METHODS: We retrospectively compared 141 patients (282 knees)
      treated with staged unicompartmental knee arthroplasty with 35 patients (70
      knees) treated with simultaneous unicompartmental knee arthroplasty to evaluate
      perioperative complications and short-term results assessed by Knee Society
      function scores and the Lower Extremity Activity Scale. RESULTS: Patients who
      underwent simultaneous unicompartmental knee arthroplasty had a shorter
      cumulative operative time (109 versus 122 minutes), a shorter cumulative length
      of hospital stay (1.7 versus 2.5 days), higher Knee Society function scores at
      most recent followup (88 versus 73), and higher Lower Extremity Activity Scale
      (12.0 versus 10.2) without a difference in perioperative complications. The
      simultaneous cohort was younger (59 versus 63 years of age) and less obese (body
      mass index 31 versus 33 kg/m(2)) than the staged group. CONCLUSIONS: Although we
      found a substantial bias for performing simultaneous unicompartmental knee
      arthroplasty in younger and less obese patients, these data suggest it can be
      performed without increasing perioperative morbidity or mortality in this patient
      population. LEVEL OF EVIDENCE: Level III, therapeutic study. See Guidelines for
      Authors for a complete description of levels of evidence.

PMID- 20683689
TI  - Progress report: the prevalence of required medical school instruction in
      musculoskeletal medicine at decade's end.
AB  - BACKGROUND: In a 2003 report, required courses in musculoskeletal medicine were
      found in only 65 of the 122 medical schools in the United States. Since then,
      national efforts to promote musculoskeletal medicine education were led by the US
      Bone and Joint Decade, the American Medical Association, the Association of
      American Medical Colleges, the American Academy of Orthopaedic Surgeons, and the
      National Board of Medical Examiners, among others. Whether these efforts resulted
      in any changes in curricula is unclear. QUESTIONS/PURPOSES: We assessed the
      change, if any, in the prevalence of required instruction in musculoskeletal
      medicine, which might be attributed to these reform efforts. METHODS: Curriculum
      requirements were ascertained by an email survey sent to all 127 medical schools
      in the United States and from the schools' websites. The presence of a
      preclinical course or block dedicated to musculoskeletal medicine was noted.
      Likewise, the requirement for a clerkship in a musculoskeletal discipline
      (comprising orthopaedic surgery, rheumatology, or physical medicine) was
      recorded. RESULTS: One hundred of the 127 medical schools in the United States
      had required preclinical courses in musculoskeletal medicine. Among the schools
      without such a course, six had a required musculoskeletal clerkship. Thus, 106
      schools had some requirement, with only 21 (17%) lacking required instruction in
      musculoskeletal medicine. This rate compares favorably with the 47% rate (57 of
      the 122 schools) reported previously. CONCLUSION: The prevalence of required
      instruction in musculoskeletal medicine is greater compared with the prevalence
      reported in previous studies. Musculoskeletal medicine appears to have attained a
      more prominent place in the curriculum at most schools.

PMID- 20683690
TI  - Management of sleep apnea in adults - functional algorithms for the perioperative
      period: Continuing Professional Development.
AB  - PURPOSE: Obstructive sleep apnea (OSA) is defined by repetitive partial or
      complete upper airway obstruction characterized by episodes of breathing
      cessation during sleep. It is the most prevalent of sleep disorders, seen in
      about one in four males and one in ten females. We reviewed current literature,
      collated expert opinion, and synthesized protocols from several institutions to
      present practical principles and functional algorithms to assist the
      anesthesiologist in the perioperative management of known and suspected OSA.
      PRINCIPAL FINDINGS: Patients with OSA may have an increase in postoperative
      adverse respiratory events, sustained arrhythmias, hypertension, and other
      cardiovascular events. The gold standard for the diagnosis of OSA is
      polysomnography. The Berlin questionnaire and the American Society of
      Anesthesiologists OSA checklist are useful screening tools, while the STOP and
      the STOP-Bang questionnaires are easy to use in adults. Patients scheduled for
      elective major surgery, who are at high risk of OSA with significant
      comorbidities, may be referred for preoperative polysomnography. Perioperative
      precautions, such as anticipation of a possible difficult airway, use of short
      acting anesthetic agents, avoidance of opioids, and extubation in a non-supine
      position, should be undertaken for known or suspected high-risk OSA patients.
      Postoperative disposition of the OSA patient should be based on the severity of
      the sleep disorder, recurrent postanesthesia care unit respiratory events, and
      the need for opioid analgesia. CONCLUSION: With adequate screening and vigilance
      in the preoperative period, risk stratification should be undertaken for known
      and suspected OSA patients, and care should be individualized. Practical
      algorithms based on current best evidence and expert opinion may be useful in the
      perioperative management.

PMID- 20683691
TI  - Molecular morphological approach to the pathological study of development and
      advancement of human breast cancer.
AB  - Since the concept of gene profile-based intrinsic subtypes was proposed, various
      studies on pathological characteristics have been performed. Particularly,
      triplenegative (TN) breast cancer, which is negative for all hormone receptors
      [estrogen receptor (ER) and/or progesterone receptor (PgR) and human epidermal
      growth factor 2 (HER2)], has been attracting attention because effects of
      endocrine and targeting therapies cannot be anticipated and thus selecting a
      treatment method is difficult. TN cancer accounts for about 10%-15% of all
      invasive breast cancer cases in Japanese, which is significantly lower than the
      incidence reported in the United States. Cytokeratin (CK) 5/6 or epidermal growth
      factor receptor (EGFR) is positive in 80%, being classified as basal-like
      carcinoma, but it should be understood that TN breast cancer and basal-like
      carcinoma are not necessarily the same. Criteria for positivity judgment of ER,
      PgR, and HER2 were established to select treatment in cases positive for each
      marker, and greater importance is attached to strict accuracy control. Inversely,
      the level of negative findings to judge TN varies among the judgment criteria. In
      any case, the prognosis of TN breast cancer is poor. Pathologically, TN breast
      cancer shows certain morphological characteristics, such as high grade and a
      pushing margin, and abnormalities of BRCA1 and p53 are frequently noted. At
      present, as no effective therapeutic strategy has been established for TN breast
      cancer, further clarification of the molecular biological characteristics of such
      cancers is needed. In addition, the incidence of TN-type ductal carcinoma in situ
      (DCIS) is low, suggesting that TN does not remain preinvasive DCIS for a
      prolonged period and that it transforms to invasive cancer in an early stage.
      Because mammary gland basal cells have characters of progenitor or stem cells
      that differentiate into both luminal epithelium and myoepithelial cells, these
      cells may be utilized for the differential diagnosis of the benignity or
      malignancy of intraductal lesions in routine pathological practice. As
      proliferation markers, such as Ki-67, and multiple gene arrays for gene signature
      are also utilized to select adjuvant therapy, analysis may progress further in
      the future.

PMID- 20683692
TI  - Series introduction Breast carcinoma and steroid hormones: a molecular
      morphological approach.

PMID- 20683693
TI  - Androgens in human breast carcinoma.
AB  - Sex steroids play important roles in the development of human breast carcinoma.
      Androgen receptor (AR) is expressed in a majority of breast carcinoma tissues.
      However, the significance of androgen actions remains largely unclear in breast
      carcinoma, differing from estrogen actions. Therefore, in this review, we
      summarized recent studies on androgens in breast carcinoma. Concentration of a
      potent androgen, 5alpha-dihydrotestosterone (DHT), was significantly higher in
      breast carcinoma tissue than in plasma, and DHT is considered to be locally
      produced from circulating androstenedione by 17beta-hydroxysteroid dehydrogenase
      type 5 and 5alpha-reductase. On the other hand, aromatase was recently reported
      as a negative regulator for intratumoral DHT production by possibly reducing the
      precursor testosterone. Androgens predominantly show antiproliferative effects in
      breast carcinoma cells, but association between AR status and the clinical
      outcome of the patient remains controversial, perhaps partly because AR status
      does not necessarily reflect androgenic action in breast carcinoma. Recently,
      molecular apocrine breast carcinoma was identified by microarray analysis.
      Molecular apocrine carcinoma was characterized by being estrogen receptor (ER)
      negative and AR positive and by being associated with increased androgen
      signaling and apocrine features. Therefore, androgenic actions may also be
      involved in apocrine features in breast carcinoma.

PMID- 20683694
TI  - Hybrid peripheral nerve sheath tumor of the nasal cavity showing schwannomatous,
      neurofibromatous, and perineuriomatous areas.
AB  - Soft tissue hybrid peripheral nerve sheath tumors (PNST), including schwannoma
      perineurioma or neurofibroma-perineurioma, have recently been described. However,
      there are no reports on hybrid PNST arising in the nasopharyngeal area. In this
      article, we report such a case. A 58-year-old Japanese man presented with nasal
      obstruction and was found to have bilateral polypoid lesions in the middle meatus
      of the nose. Subsequently, nasal polypectomy was performed. Histologically, the
      tumor consisted of three components including schwannoma, neurofibroma, and
      perineurioma. Immunohistochemically, schwannoma, neurofibroma, and perineurioma
      components were positive for S-100 protein, CD34, and epithelial membrane
      antigen, respectively. In conclusion, this is the first case of hybrid PNST
      reported to occur in the nasopharyngeal area. Pathologists should be aware of the
      possibility that hybrid PNST may present outside soft tissue.

PMID- 20683695
TI  - Diagnostic pitfall on the histological spectrum of adult-onset renal carcinoma
      associated with Xp11.2 translocations/TFE3 gene fusions.
AB  - Renal cell carcinoma (RCC) associated with Xp11.2 translocation/TFE3 gene fusion
      recently has been found. In this article, we demonstrate an unusual features of
      such a case. A 73-year-old Japanese woman presented with macroscopic hematuria.
      The imaging examinations disclosed the renal tumor. Histological examination
      showed the finding of ASPL-TFE3 RCC, which was characterized by papillary,
      alveolar, or solid growth of voluminous cell with clear and eosinophilic cells,
      and stromal psammoma body and hyaline nodules. Additionally, shrunken nuclei,
      thick cell border, and perinuclear clearing characteristic of chromophobe renal
      cell carcinoma were observed in the alveolar growth area and the transitional
      zone between stromal hyalinization, and osseous metaplasia was identified.
      Immunohistochemically, nuclei of tumorous cell were diffusely positive for TFE3.
      A RT-PCR study revealed the ASPL-TFE3 chimeric transcript. Finally, pathologists
      should recognize that the histology of RCC associated with Xp11.2
      translocation/TFE3 gene fusion may focally resemble that of chromophobe RCC, but
      TFE3 immunohistochemistry and molecular genetic study may be helpful in the
      differential diagnosis. Moreover, osseous metaplasia as well as psammoma bodies
      should be added to the histological spectrum of the stromal change in RCC
      associated with Xp11.2 translocations/TFE3 gene fusions.

PMID- 20683696
TI  - Primary undifferentiated carcinoma of the small intestine: an immunohistochemical
      study and review of the literature.
AB  - Primary undifferentiated carcinoma of the small intestine is an extremely rare
      neoplasm. Here, we report a case of primary undifferentiated carcinoma that arose
      from the ileum in a 65-year-old woman. Laboratory data revealed anemia and
      slightly elevated inflammatory parameters. Computed tomography showed a
      heterogeneous mass in the pelvic cavity, and magnetic resonance imaging revealed
      that the margin of the tumor mass was clear. Positron emission tomography using
      (18)F-fluoro-2-deoxy-D: -glucose (FDG) showed accumulation of FDG on the tumor
      mass with a standardized uptake value of 8.3. Partial resection of the ileum to
      remove the tumor was performed under a clinical diagnosis of small intestinal
      carcinoma. The tumor was nodulated and had a circumscribed margin 6.5 x 5.5 x 4
      cm in diameter. Microscopically, the tumor was composed of giant polygonal cells
      with cellular atypia. Immunohistochemical examination revealed that the tumor
      cells expressed epithelial markers including AE1/AE3, CAM5.2, and EMA; however,
      lymphocytic, mesenchymal, and gastrointestinal stromal tumor markers were not
      expressed. We made a final diagnosis of primary undifferentiated carcinoma of the
      small intestine. The prognosis of patients with undifferentiated carcinoma of the
      small intestine is very poor. To improve the outcome of treatment, early and
      accurate diagnosis is essential, and additional therapy, including multimodality
      adjuvant therapy or the administration of novel molecular targeted drugs, should
      be considered.

PMID- 20683697
TI  - Immunohistochemical and ultrastructural characterization of the signet-ring cell
      carcinoma component in a case of urothelial carcinoma of the urinary bladder.
AB  - Characterization of the signet-ring cell carcinoma (sig) component of a
      urothelial carcinoma (UC) in the urinary bladder of a 64-year-old man, obtained
      by transurethral resection of bladder tumor (TUR-BT), is reported. In the present
      case, a characteristic sig component was detected in approximately 20% of UC, G2
      tissues. The sig cells were morphologically similar to those found in gastric
      cancers and were positively stained with periodic acid-Schiff reaction and Alcian
      blue and mucicarmine stains. Immunohistochemically, the sig cells were
      selectively positive for carcinoembryonic antigen (CEA), MUC2, and MUC5AC. These
      immunohistochemical characteristics were similar to those of sig cells in the
      stomach, except for the positivity with MUC2. It is interesting to note that
      CAM5.2-positive sig cells were surrounded by CAM5.2-positive UC cells in a solid
      nest with no apparent associated adenocarcinoma element. In addition, the
      ultrastructure of sig cells showed multivacuolar cytoplasmic mucin, which proved
      to be similar to the ultrastructure of gastric cancers. In the present case of
      UC, G2 was associated with a sig component. Regarding the origin of the sig
      component in the bladder, it has been suggested that MUC2-positive sig cells in
      the bladder might be derived directly from metaplasia of UC, without an
      associated adenocarcinoma component. From this perspective, it may be noteworthy
      that sig cells in the bladder were selectively positive for MUC2, exhibiting
      common antigenicity with mucous cells of the gastric intestinal metaplasia.
      Because UC associated with a sig component carries a worse prognosis than
      ordinary UC, the presence of the sig component in any UC should be evaluated even
      within TUR-BT tissues, as in the present case.

PMID- 20683698
TI  - Differential expression patterns of the tight junction-associated proteins
      occludin and claudins in secretory and mature ameloblasts in mouse incisor.
AB  - Tight junctions (TJs) function primarily as a barrier against paracellular
      transport between epithelial cells and are composed mainly of occludin (OLD) and
      claudins (CLDs). The CLD family consists of 24 members that show tissue- or cell
      specific expression. Ameloblasts, which originate from the oral epithelium, form
      enamel, and enamel proteins and minerals are transported across the ameloblastic
      layer during amelogenesis. We immunohistochemically examined the distribution
      patterns of TJs in ameloblasts by observing the expression patterns of OLD and
      CLDs (CLD-1 to CLD-10). Secretory ameloblasts contained OLD and CLD-1, -8, and -9
      at the distal end of the cell. In mature ameloblasts, OLD and CLD-1, -6, -7, -8, 
      9, and -10 were present mainly at both the distal and proximal ends of the cell,
      regardless of whether the ameloblasts were ruffle-ended or smooth-ended. Mature
      ameloblasts in which only the proximal ends were stained for OLD and CLDs were
      also found. These results indicate that the expression patterns of CLDs and the
      distribution patterns of TJs change drastically between the secretory and mature
      ameloblast stages, suggesting that these patterns reflect the different functions
      of these cells, specifically in the transport of proteins and ions for enamel
      formation.

PMID- 20683699
TI  - Human primary cultured hepatic stellate cells can be cryopreserved.
AB  - We compared the morphological and functional characteristics of cultured unfrozen
      hepatic stellate cells (HSCs) and cryopreserved HSCs obtained from human livers.
      We used liver tissues obtained by surgical resection from patients with
      metastatic liver cancer or with hepatocellular carcinoma. HSCs were isolated and
      allowed to spread in culture. Comparison of morphological and functional features
      between the unfrozen HSCs and cryopreserved HSCs was performed at each passage
      using the following techniques: light microscopy, immunohistochemistry, cell
      growth curve, metallothionein (MTT) assay, and PI staining, Western blot, real
      time polymerase chain reaction (PCR), and gene expression analysis using
      microarrays. The purity of HSCs was more than 90% in all passages. alpha-Smooth
      muscle actin (SMA-)positive HSCs gradually increased in successive passages, and
      the positive cell rate and rate of increase in cell number were similar in both
      groups. Expression of platelet-derived growth factor (PDGF) receptor,
      transforming growth factor (TGF)-beta receptor, and alpha-SMA mRNAs and protein
      was similar during each passage in the two groups. Gene expression was nearly
      identical at each passage in unfrozen and frozen/thawed samples obtained from the
      same patient. In conclusion, an adequate protocol for the cryopreservation of
      human primary cultured HSCs could be established.

PMID- 20683700
TI  - Effects of low protein intake on the development of the remaining kidney in
      subtotally nephrectomized immature rats: expression of inducible and endothelial
      NO synthase.
AB  - We examined the effects of low protein intake on the development of the remaining
      kidney in subtotally (5/6) nephrectomized immature rats. Three-week-old rats were
      kept on a diet containing either 12% protein (Lp rats) or 18% protein (Np rats)
      for 4 or 8 weeks after subtotal nephrectomy (SUNx). In Western blot analysis, the
      endothelial NO synthase (eNOS) protein expression of the Lp rats was
      significantly higher than that of the Np rats at 4 weeks after SUNx.
      Immunohistochemically, more inducible NO synthase (iNOS)-positive cells were
      observed in the Np rats than in the Lp rats 4 weeks after SUNx in the distal
      tubules. In semiquantitative RT-PCR, the expression of renin mRNA was
      significantly lower in the Lp rats than in the Np rats at 4 and 8 weeks after
      SUNx. These findings reveal that protein restriction is effective in preventing
      renal failure of immature rats and that the changes in the expression levels of
      renin, eNOS, and iNOS is involved in the process of this prevention.

PMID- 20683701
TI  - Embryonic development of hair follicle pluripotent stem (hfPS) cells.
AB  - Our laboratory discovered nestin-expressing hair follicle stem cells and
      demonstrated their pluripotency. We have shown that nestin-positive and K15
      negative multipotent hair follicle stem cells are located above the hair follicle
      bulge, and we termed these cells hair follicle pluripotent stem (hfPS) cells. We
      have previously shown that hair follicle stem cells can regenerate peripheral
      nerve and spinal cord. In the present study, we describe the embryonic
      development of the hair follicle stem cell area (hfPSCA), which is located above
      the bulge and below the sebaceous glands in the adult mouse. At embryonic day
      16.5 (E16.5) of nestindriven GFP (ND-GFP) transgenic mice, which express nestin
      in hfPS cells, the ND-GFP hair follicle stem cells are located in mesenchymal
      condensates. At postnatal day 0 (P0), the ND-GFP-expressing cells are migrating
      to the upper part of the hair follicle from the dermal papilla. At P3, keratin 15
      (K15)-positive cells, derived from ND-GFP dermal papilla cells, are located in
      the outer-root sheath and basal layer of the epidermis. By P10, the ND-GFP have
      formed the K15-positive outer-root sheath as well as the ND-GFP hfPSA. These
      results suggest that ND-GFP hfPS cells in the dermal papilla form nestin
      expressing hair follicle stem cells in the first hair cycle. These observations
      provide new insight into the origins of hfPS cells and the hfPSCA.

PMID- 20683702
TI  - [Undescended testis: aspects of treatment].
AB  - Undescended testis (UDT) is the most frequent congenital malformation affecting
      1% of 1-year-old mature birth boys. If untreated UDT leads to progressive
      histological changes with impaired spermatogenesis and an increasing risk of
      testicular cancer. For clinical reasons palpable testes should be differentiated
      from impalpable testes. Spontaneous testicular descent can be expected only
      before 6 months of age. Subsequently, treatment should start without delay and be
      finished before the child has reached the age of 1 year. Surgery is the
      cornerstone of treatment. Inguinal approaches are standard practice for palpable
      testes, whereas laparoscopy is used in non-palpable testes. Hormonal treatment is
      ineffective for inducing testicular descent but facilitates germ cell maturation
      and an improvement in fertility potential. Only early treatment of UDT reduces
      germ cell loss, improves fertility and reduces the risk of testicular cancer.

PMID- 20683703
TI  - Availability and use of hip protectors in residents of nursing homes.
AB  - SUMMARY: Potential predictors of availability and use of hip protectors were
      studied in residents of 48 nursing homes. The likelihood of being offered a hip
      protector was reduced in men, in residents with very low or very high care needs,
      in residents with migration background, and in recipients of welfare aid.
      INTRODUCTION: The purpose of this study is to analyze potential predictors of
      availability and use of hip protectors in residents of nursing homes. METHODS: In
      48 German nursing homes, individual information on availability and use of hip
      protectors was collected from all institutionalized residents (3,924 residents;
      78.2% women). Information on nursing home characteristics was obtained by
      telephone interview. The effect of individual variables and of nursing home
      characteristics on hip protector availability and use was estimated using
      multilevel logistic regression analyses. RESULTS: The prevalence of hip
      protectors being made available was 10.0% in women and 6.2% in men. Sixty-four
      percent of those with a hip protector used it during the 4 weeks prior to the
      examination. The likelihood of being offered a hip protector was reduced in men
      (odds ratio (OR), 0.59; 95% confidence interval (CI), 0.43; 0.83), in residents
      with very low or very high care needs (OR, 0.32; 95% CI, 0.18; 0.56 and OR, 0.55;
      95% CI, 0.38; 0.79, respectively), in residents with a migration background (OR,
      0.30; 95% CI, 0.09; 0.99), and in recipients of welfare aid (OR, 0.60; 95% CI,
      0.44; 0.81). Nursing home characteristics such as the size of the nursing home or
      staff participation rate in training measures had no effect on hip protector
      availability and use. CONCLUSION: Predictors of hip protector availability were
      sex, the degree of care need, migration status, and welfare aid. The lower
      availability of hip protectors in residents with welfare aid and migration status
      may be an indicator for health inequality in the German health system.

PMID- 20683704
TI  - Osteoporosis pharmacotherapy following bone densitometry: importance of patient
      beliefs and understanding of DXA results.
AB  - SUMMARY: Persistence with osteoporosis therapy remains low and identification of
      factors associated with better persistence is essential in preventing
      osteoporosis and fractures. In this study, patient understanding of dual energy X
      ray absorptiometry (DXA) results and beliefs in effects of treatment were
      associated with treatment initiation and persistence. INTRODUCTION: The purpose
      of this study is to examine patient understanding of their DXA results and
      evaluate factors associated with initiation of and persistence with prescribed
      medication in first-time users of anti-osteoporotic agents. Self-reported DXA
      results reflect patient understanding of diagnosis and may influence acceptance
      of osteoporosis therapy. To improve patient understanding of DXA results, we
      provided written information to patients and their referring general practitioner
      (GP), and evaluated factors associated with osteoporosis treatment initiation and
      1-year persistence. METHODS: Information on diagnosis was mailed to 1,000
      consecutive patients and their GPs after DXA testing. One year after, a
      questionnaire was mailed to all patients to evaluate self-report of DXA results,
      drug initiation and 1-year persistence. Quadratic weighted kappa was used to
      estimate agreement between self-report and actual DXA results. Multivariable
      logistic regression was used to evaluate predictors of understanding of
      diagnosis, and correlates of treatment initiation and persistence. RESULTS: A
      total of 717 patients responded (72%). Overall, only 4% were unaware of DXA
      results. Agreement between self-reported and actual DXA results was very good
      (kappa = 0.83); younger age and glucocorticoid use were associated with better
      understanding. Correctly reported DXA results was associated with treatment
      initiation (OR 4.3, 95% CI 1.2-15.1, p = 0.02), and greater beliefs in drug
      treatment benefits were associated with treatment initiation (OR 1.4, 95%CI 1.1
      1.9, p = 0.006) and persistence with therapy (OR 1.8, 95% CI 1.2-2.7, p = 0.006).
      CONCLUSION: Our findings suggest that written information provides over 80% of
      patients with a basic understanding of their DXA results. Communicating results
      in writing may improve patient understanding thereby also improve osteoporosis
      management and prevention.

PMID- 20683705
TI  - Effects of HIV infection and antiretroviral therapy with ritonavir on induction
      of osteoclast-like cells in postmenopausal women.
AB  - SUMMARY: Ritonavir (RTV) is a commonly used antiretroviral associated with bone
      loss. We show that peripheral blood mononuclear cells (PBMCs) from human
      immunodeficiency virus (HIV)-positive women on RTV are more likely to
      differentiate into osteoclast-like cells when cultured with their own sera than
      PBMCs and sera from HIV- women or HIV+ on other antiretrovirals. INTRODUCTION:
      RTV increases differentiation of human adherent PBMCs to functional osteoclasts
      in vitro, and antiretroviral regimens containing RTV have been associated with
      low bone mineral density (BMD) and bone loss. METHODS: BMD, proresorptive
      cytokines, bone turnover markers (BTMs), and induction of osteoclast-like cells
      from adherent PBMCs incubated either with macrophage colony-stimulating factor
      (MCSF) and receptor activator of nuclear factor kappaB ligand (RANKL) or with
      autologous serum were compared in 51 HIV- and 68 HIV+ postmenopausal women.
      RESULTS: BMD was lower, and serum proresorptive cytokines and BTMs were higher in
      HIV+ versus HIV- women. Differentiation of osteoclast-like cells from adherent
      PBMCs exposed to either MCSF/RANKL or autologous serum was greater in HIV+ women.
      Induction of osteoclast-like cells was greater from PBMCs exposed to autologous
      sera from HIV+ women on RTV-containing versus other regimens (172 +/- 14% versus
      110 +/- 10%, p < 0.001). Serum-based induction of osteoclast-like cells from
      adherent PBMCs correlated with certain BTMs but not BMD. CONCLUSIONS: HIV
      infection and antiretroviral therapy are associated with higher BTMs and
      increased differentiation of osteoclast-like cells from adherent PBMCs,
      especially in women on regimens containing RTV. HIV+ postmenopausal women
      receiving RTV may be at greater risk for bone loss.

PMID- 20683707
TI  - Economic evaluation of dose-response resistance training in older women: a cost
      effectiveness and cost-utility analysis.
AB  - SUMMARY: We estimated the incremental cost-effectiveness of a once-weekly or
      twice-weekly resistance training intervention compared with balance and tone
      classes in terms of falls prevented and quality-adjusted life years (QALYs)
      gained. Both resistance training interventions were more likely to save health
      care resource money and offer better health outcomes for falls prevention than
      balance and tone classes. INTRODUCTION: This study aims to estimate the
      incremental cost-effectiveness and cost-utility of a once-weekly or twice-weekly
      resistance training intervention compared with twice-weekly balance and tone
      classes in terms of falls prevented and QALYs gained. METHODS: Economic
      evaluation was conducted concurrently with a three-arm randomized controlled
      trial including 155 community-dwelling women aged 65 to 75 years, Mini Mental
      State Examination >=24, and visual acuity 20/40 or better. Participants received
      the once-weekly resistance training (n = 54), the twice-weekly resistance
      training (n = 51) or the twice-weekly balance and tone (the comparator) classes
      (n = 50) for 1 year. Measurements included the number of falls for each
      participant, healthcare resource utilization, and associated costs over 9 months;
      health status was assessed using the EQ-5D and SF-6D to calculate QALYs. RESULTS:
      Based on the point estimates from our base case analysis, we found that both once
      and twice-weekly resistance training groups were less costly (p < 0.05) and more
      effective than twice-weekly balance and tone classes. The incremental QALYs
      assessed using the SF-6D were 0.003 for both the once- and twice-weekly
      resistance training groups, compared with the twice-weekly balance and tone
      classes. The incremental QALYs assessed using the EQ-5D were 0.084 for the once
      weekly and 0.179 for the twice-weekly resistance training groups, respectively,
      compared with the twice-weekly balance and tone classes. CONCLUSIONS: An
      individually tailored resistance training intervention delivered once or twice
      weekly provided better value for money for falls prevention than balance and tone
      classes.

PMID- 20683706
TI  - Fragility fractures and the osteoporosis care gap in women: the Canadian
      Multicentre Osteoporosis Study.
AB  - Canadian women over 50 years old were studied over a 10-year period to see if
      those who sustained a fracture (caused by minimal trauma) were receiving the
      recommended osteoporosis therapy. We found that approximately half of these women
      were not being treated, indicating a significant care gap in osteoporosis
      treatment. INTRODUCTION: Prevalent fragility fracture strongly predicts future
      fracture. Previous studies have indicated that women with fragility fractures are
      not receiving the indicated treatment. We aimed to describe post fracture care in
      Canadian women using a large, population-based prospective cohort that began in
      1995-1997. METHODS: We followed 5,566 women over 50 years of age from across
      Canada over a period of 10 years in the Canadian Multicentre Osteoporosis Study.
      Information on medication use and incident clinical fragility fractures was
      obtained during a yearly questionnaire or interview and fractures were confirmed
      by radiographic/medical reports. RESULTS: Over the 10-year study period, 42-56%
      of women with yearly incident clinical fragility fractures were not treated with
      an osteoporosis medication. During year 1 of the study, 22% of the women who had
      experienced a fragility fracture were on treatment with a bisphosphonate and 26%
      were on hormone therapy (HT). We were not able to differentiate HT use for
      menopause symptoms vs osteoporosis. Use of bisphosphonate therapy increased over
      time; odds ratio (OR) for use at year 10 compared to use at year 1 was 3.65 (95%
      confidence interval (CI) 1.83-7.26). In contrast, HT use declined, with an OR of
      0.07 (95%CI 0.02-0.24) at year 10 compared to year 1 of the study. CONCLUSION: In
      a large population-based cohort study, we found a therapeutic care gap in women
      with osteoporosis and fragility fractures. Although bisphosphonate therapy usage
      improved over time, a substantial gap remains.

PMID- 20683708
TI  - Deleting Rac1 improves vertebral bone quality and resistance to fracture in a
      murine ovariectomy model.
AB  - SUMMARY: The roles of Rac1 and Rac2 in regulating osteoclast-mediated bone
      quality in postmenopausal osteoporosis were evaluated using an ovariectomized
      murine model. Animals' bone composition and architecture were evaluated. Our
      results demonstrate that the deletion of Rac1 increases vertebral bone quality
      compared to wild-type bones in an ovariectomized model. INTRODUCTION: To
      determine the roles of the Rho family small GTPases Rac1 and Rac2 in regulating
      osteoclast-mediated bone quality in a model of postmenopausal osteoporosis.
      METHODS: Twelve-month-old female mice from three genotypes-wild type (WT), Rac1
      null (LysM.Rac1 KO), and Rac2 null (Rac2KO)--were studied in control and
      ovariectomized groups (mice previously ovariectomized at 4 months of age).
      Animals were sacrificed at 12 months of age, and the femora and vertebrae were
      harvested for mechanical testing, bone densitometry, micro-computed tomography,
      and histomorphometric analyses to evaluate bone mineralization and architecture.
      The results were compared between groups using ANOVA and LSD post-hoc tests.
      RESULTS: We observed that LysM.Rac1 KO mice showed higher vertebral bone mineral
      density compared to WT in both control and ovariectomized groups. Consistent with
      this finding, LysM.Rac1 KO vertebrae showed increased resistance to fracture and
      increased trabecular connectivity compared to WT in both groups. Micro-CT
      analysis revealed that Rac2KO ovariectomized vertebrae have more trabecular bone
      compared to WT and LysM.Rac1 KO, but this did not translate into increased
      fracture resistance. CONCLUSION: Our results demonstrate that the deletion of
      Rac1 increases vertebral bone quality compared to WT bones in a postmenopausal
      osteoporosis model.

PMID- 20683709
TI  - Catechin stimulates osteogenesis by enhancing PP2A activity in human mesenchymal
      stem cells.
AB  - SUMMARY: Using human mesenchymal stem cells, we identified catechin from a panel
      of herbal ingredients and Chinese traditional compounds with the strongest
      osteogenic effects. Catechin increased alkaline phosphatase activity, calcium
      deposition, and mRNA expression of Runx2 and osteocalcin. We further clarified
      the signaling pathway that catechin mediated to stimulate osteogenesis.
      INTRODUCTION: Human mesenchymal stem cells (hMSCs), useful as a species specific
      cell culture system for studying cell lineage differentiation, were examined as a
      tool to identify novel herbal ingredients and Chinese traditional compounds for
      enhancing osteogenesis. METHODS: Immortalized and primary hMSCs were induced in
      osteogenic induction medium in the presence of a variety of herbal ingredients
      and Chinese traditional compounds and osteogenic differentiation was evaluated by
      histochemical assays and quantitative RT-PCR. RESULTS: Using immortalized hMSCs,
      we first identified catechin, 18beta-glycyrrhetinic acid, baishao, and danggui
      with osteogenic properties, which enhanced calcium deposition at the dose without
      significant cytotoxic effects. Primary hMSCs were then applied for confirming the
      osteogenic effects of catechin, which increased alkaline phosphatase activity,
      calcium deposition, and mRNA expression of Runx2 and osteocalcin. We further
      found the extracellular signal-regulated kinase (ERK) pathway was downregulated
      upon stimulation with catechin. Catechin increased the level and activity of
      protein phosphatases 2A (PP2A) that dephosphorylates ERK kinase (MEK) and ERK.
      Further, PP2A inhibitor, okadaic acid, abolished the effect of catechin-mediated
      inactivation of ERK and stimulation of osteogenesis. The blocking effect of
      okadaic acid on osteogenesis was further reversed by PD98059, a specific
      inhibitor of MEK. Co-immunoprecipitation revealed the association of PP2A to both
      MEK and ERK. CONCLUSIONS: These studies propose catechin enhanced osteogenesis by
      increasing the PP2A level that inhibits the MEK and ERK signaling in hMSCs. These
      results prove the concept of using hMSCs as a convenient tool for rapid and
      consistent screening of the osteogenic herbal ingredients and traditional Chinese
      compounds.

PMID- 20683710
TI  - Prevalence of risk factors for fractures and use of DXA scanning in Danish women.
      A regional population-based study.
AB  - SUMMARY: To determine the relationship between risk factors and use of DXA scans.
      Our study showed a relatively high use of DXA in low-risk women and the
      relatively low coverage in women with multiple risk factors. Moreover, distance
      to DXA clinics, age, and socio-economic factors are associated with the use of
      DXA. INTRODUCTION: To determine the relationship between risk factors for
      fracture and use of DXA scans in Danish women in relation to distance to DXA
      clinics and socio-economic factors. METHODS: From the Danish National Civil
      Register we randomly selected 5,000 women aged 40-90 years living in the region
      of Southern Denmark to receive a mailed questionnaire concerning risk factors for
      fractures. RESULTS: The respondents rate was 84% and 77% of the invited
      population were available for analysis. A total of 10.3% of the women without
      risk factors and only 36% of the women with three or more risk factors had a
      history of DXA. The likelihood of a history of DXA was higher with increasing
      FRAX(TM) 10-year risk; i.e., 8.7% and 30.2% in patients with a 10-year fracture
      risk of 0-14.9% and 25-100%, respectively. In women with less than 10 km to
      nearest DXA facility, 20.2% had a history of DXA, while 11.5% of those with more
      than 40 km to the nearest scanner had a history of DXA. Logistic regression
      analysis showed that distance, fracture risk, oral glucocorticoids, low-energy
      fracture, conditions associated with secondary osteoporosis, low BMI, history of
      falls, age 65-79 years, spouse status, and income were significantly associated
      with having a history of DXA. CONCLUSIONS: Our study showed a relatively high use
      of DXA in low-risk women and the relatively low coverage in women with multiple
      risk factors. Moreover, distance to DXA clinics, age, and a number of socio
      economic factors are associated with the use of DXA.

PMID- 20683711
TI  - Does birthweight predict bone mass in adulthood? A systematic review and meta
      analysis.
AB  - SUMMARY: This systematic review and meta-analysis assessed the strength and
      magnitude of the association between birthweight and adult bone mass. Higher
      birthweight was associated with higher bone mineral content of the spine and hip
      in adult men and women at ages between 18 and 80 years across a range of
      settings. INTRODUCTION: The aim of this review was to assess the strength and
      magnitude of the association between early size and adult bone mass. METHODS:
      Systematic review and meta-analysis of studies that assessed the association
      between birthweight or weight at 1 year, and bone mineral content (BMC) or bone
      mineral density (BMD) in adulthood. RESULTS: Fourteen studies met inclusion
      criteria. Nine assessed the relationship between birthweight and lumbar spine
      BMC, most showing that higher birthweight was associated with greater adult BMC.
      Meta-analysis demonstrated that a 1 kg increase in birthweight was associated
      with a 1.49 g increase in lumbar spine BMC (95% CI 0.77-2.21). Birthweight was
      not associated with lumbar spine BMD in 11 studies. In six studies, considering
      the relationship between birthweight and hip BMC, most found that higher
      birthweight was associated with greater BMC. Meta-analysis demonstrated that a 1
      kg increase in birthweight was associated with a 1.41 g increase in hip BMC (95%
      CI 0.91-1.91). Seven studies considered the relationship between birthweight and
      hip BMD and, in most, birthweight was not a significant predictor of hip BMD.
      Three studies assessing the relationship between weight at 1 year and adult bone
      mass all reported that higher weight at one was associated with greater BMC of
      the lumbar spine and hip. CONCLUSIONS: Higher birthweight is associated with
      greater BMC of the lumbar spine and hip in adulthood. The consistency of these
      associations, across a range of settings, provides compelling evidence for the
      intrauterine programming of skeletal development and tracking of skeletal size
      from infancy to adulthood.

PMID- 20683712
TI  - Sunlight exposure or vitamin D supplementation for vitamin D-deficient non
      western immigrants: a randomized clinical trial.
AB  - Vitamin D deficiency is very common in non-western immigrants. In this randomized
      clinical trial, vitamin D 800 IU/day or 100,000 IU/3 months were compared with
      advised sunlight exposure. Vitamin D supplementation was more effective than
      advised sunlight exposure in improving vitamin D status and lowering parathyroid
      hormone levels. INTRODUCTION: Vitamin D deficiency (25-hydroxyvitamin D [25(OH)D]
      < 25 nmol/l) is common among non-western immigrants. It can be treated with
      vitamin D supplementation or sunlight exposure. METHODS: To determine whether the
      effect of vitamin D(3) supplementation (daily 800 IU or 100,000 IU/3 months) or
      sunlight exposure advice is similar with regard to serum 25(OH)D and parathyroid
      hormone (PTH) concentrations. Randomized clinical trial in 11 general practices
      in The Netherlands. Non-western immigrants, aged 18-65 years (n = 232) and serum
      25(OH)D < 25 nmol/l were randomly assigned to supplementation (daily 800 IU or
      100,000 IU/3 months) or advice for sunlight exposure for 6 months (March
      September). Blood samples were collected at baseline, during treatment (3 months,
      6 months), and at follow-up (12 months). Statistical analysis was performed with
      multilevel regression modelling. RESULTS: The intention-to-treat analysis
      included 211 persons. Baseline serum 25(OH)D was 22.5 +/- 11.1 nmol/l. After 6
      months, mean serum 25(OH)D increased to 53 nmol/l with 800 IU/day, to 50.5 nmol/l
      with 100,000 IU/3 months, and to 29.1 nmol/l with advised sunlight exposure
      (supplementation vs sunshine p < 0.001). Serum PTH decreased significantly in all
      groups after 3 months, more in the supplementation groups than in the advised
      sunlight group (p < 0.05). There was no significant effect on physical
      performance and functional limitations. CONCLUSION: Vitamin D supplementation is
      more effective than advised sunlight exposure for treating vitamin D deficiency
      in non-western immigrants.

PMID- 20683713
TI  - Vertebral fractures in Gaucher disease type I: data from the French
      "Observatoire" on Gaucher disease (FROG).
AB  - Gaucher disease type 1 (GD1), results in a range of skeletal complications
      including osteopenia, osteoporosis, and osteonecrosis, but there is little
      published information regarding vertebral fractures. Findings from this
      observational study indicated that the prevalence of vertebral fractures in a
      cohort of adult French GD1 patients is approximately 15%. INTRODUCTION: The aim
      of the study was to assess the prevalence and characteristics of vertebral
      fractures in a cohort of adult patients with GD1. METHODS: This study was
      performed in adult patients with GD1 based on a detailed and complete clinical
      examination. For all patients for whom vertebral fractures were reported, a
      specific questionnaire was sent to physicians, and imaging data were collected,
      when available, for centralized analysis. RESULTS: Data were collected from a
      total of 105 adult GD1 patients. Bone complications were reported in 85% of
      patients, among whom vertebral fractures were diagnosed in 16 (15%); seven women
      and nine men (mean age, 45 years). We observed five patients with multiple
      vertebral fractures and one patient in whom the T3 vertebra was fractured. Most
      of these patients did not report fracture-related back pain. CONCLUSIONS: The
      prevalence of vertebral fractures in this cohort of adult patients with GD1 was
      15%. Greater awareness of the natural history of vertebral fractures in GD1, and
      rigorous monitoring of bone fragility and spine involvement in affected patients,
      should allow earlier detection and initiation of treatment tailored toward
      improving bone status.

PMID- 20683714
TI  - A pediatric case of life-threatening airway obstruction caused by a
      cervicomediastinal thymic cyst.
AB  - Most patients with thymic cysts complain of a slowly enlarging, asymptomatic
      cervical mass. Only 6-10% suffer dysphagia, dyspnoea, stridor, cervical pain or
      vocal paralysis. In some rare cases sudden onset of severe dyspnoea or asphyxia
      is the first symptom, especially in neonates and small infants. We report a
      unique case of a 20-month-old child, who required emergency tracheal intubation
      due to asphyxia. Cervicomediastinal thymic cyst might need to be included in
      causes of life-threatening airway obstruction in young children.

PMID- 20683715
TI  - The quorum-sensing effect of aerobic granules on bacterial adhesion, biofilm
      formation, and sludge granulation.
AB  - Quorum sensing (QS) through signal chemical molecules is known to be essential to
      bacterial adhesion and biofilm formation. In this study, the QS ability of
      aerobic granules--a special form of biofilms used for biological wastewater
      treatment--was investigated and compared with that of conventional activated
      sludge flocs. A novel sectional membrane bioreactor was used together with a flow
      cell to evaluate the possible influence of signal chemicals produced by the
      source sludge on the growth mode of bacterial cells. The results demonstrate the
      apparent production of QS chemicals from granules and its impact on initial cell
      attachment and granule formation. When granules were used as the signal-producing
      biomass, the attached-growth mode was dominant for the free cells, and the
      biofilm formation rate in the flow-cell was about ten times faster than in cases
      which used activated sludge as the signal source biomass. In addition, the
      intracellular extract from mature granules significantly accelerated the sludge
      granulation process. It is argued that the production and expression of QS signal
      chemicals from granules and granule precursors might have induced the gene
      expression of bacteria in suspension for attached growth rather than suspended
      growth, leading to granule formation and its stable structure.

PMID- 20683716
TI  - Resveratrol content and expression of phenylalanine ammonia-lyase and stilbene
      synthase genes in rolC transgenic cell cultures of Vitis amurensis.
AB  - Resveratrol, a naturally occurring polyphenol, has been reported to exhibit a
      wide range of valuable biological and pharmacological properties. In the present
      investigation, we show that transformation of Vitis amurensis Rupr. with the
      oncogene rolC of Agrobacterium rhizogenes increased resveratrol production in the
      two transformed callus cultures 3.7 and 11.9 times. The rolC-transformed calli
      were capable of producing 0.099% and 0.144% dry weight of resveratrol. We
      characterized phenylalanine ammonia-lyase (PAL) and stilbene synthase (STS) gene
      expression in the two rolC transgenic callus cultures of V. amurensis. In the
      rolC transgenic culture with higher resveratrol content, expression of VaPAL3,
      VaSTS3, VaSTS4, VaSTS5, VaSTS6, VaSTS8, VaSTS9, and VaSTS10 was increased; while
      in the rolC culture with lower resveratrol content, expression of VaPAL3 and
      VaSTS9 was increased. We suggest that transformation of V. amurensis calli with
      the rolS gene induced resveratrol accumulation via selective enhancement of
      expression of individual PAL and STS genes involved in resveratrol biosynthesis.
      We compared the data on PAL and STS gene expression in rolC transgenic calli with
      the previously obtained results for rolB transgenic calli of V. amurensis. We
      propose that the transformation of V. amurensis with the rolC and rolB genes of
      A. rhizogenes increased resveratrol accumulation through different regulatory
      pathways.

PMID- 20683717
TI  - Arbuscular mycorrhizal fungus enhances P acquisition of wheat (Triticum aestivum
      L.) in a sandy loam soil with long-term inorganic fertilization regime.
AB  - The P efficiency, crop yield, and response of wheat to arbuscular mycorrhizal
      fungus (AMF) Glomus caledonium were tested in an experimental field with long
      term (19 years) fertilizer management. The experiment included five fertilizer
      treatments: organic amendment (OA), half organic amendment plus half mineral
      fertilizer (1/2 OM), mineral fertilizer NPK, mineral fertilizer NK, and the
      control (without fertilization). AMF inoculation responsiveness (MIR) of wheat
      plants at acquiring P were estimated by comparing plants grown in unsterilized
      soil inoculated with G. caledonium and in untreated soil containing indigenous
      AMF. Without AMF inoculation, higher crop yields but lower colonization rates
      were observed in the NPK and two OA-inputted treatments, and NPK had
      significantly (P < 0.05) lower impacts on organic C and available P in soils and
      thereby P acquisition of wheat plants compared with OA and 1/2 OM. G. caledonium
      inoculation significantly (P < 0.05) increased colonization rates with the NPK
      and two P-deficient treatments but significantly (P < 0.05) increased vegetative
      biomass, crop yield, and P acquisition of wheat as well as soil alkaline
      phosphatase (ALP) activity, only with the NPK treatment. This gave an MIR of ca.
      45% on total P acquisition of wheat plants. There were no other remarkable MIRs.
      It suggested that the MIR is determined by soil available P status, and rational
      combination of AMF with chemical NPK fertilizer can compensate for organic
      amendments by improving P-acquisition efficiency in arable soils.

PMID- 20683718
TI  - Threonine aldolases-screening, properties and applications in the synthesis of
      non-proteinogenic beta-hydroxy-alpha-amino acids.
AB  - Threonine aldolases (TAs) constitute a powerful tool for catalyzing carbon-carbon
      bond formations in synthetic organic chemistry, thus enabling an enantio- and
      diastereoselective synthesis of beta-hydroxy-alpha-amino acids. Starting from the
      achiral precursors glycine and an aldehyde, two new stereogenic centres are
      formed in this catalytic step. The resulting chiral beta-hydroxy-alpha-amino acid
      products are important precursors for pharmaceuticals such as thiamphenicol, a L:
      -threo-phenylserine derivative or L: -threo-3,4-dihydroxyphenylserine. TAs are
      pyridoxal-5-phosphate-dependent enzymes, which, in nature, catalyze the cleavage
      of L: -threonine or L: -allo-threonine to glycine and acetaldehyde in a glycine
      biosynthetic pathway. TAs from a broad number of species of bacteria and fungi
      have been isolated and characterised as biocatalysts for the synthesis of beta
      hydroxy-alpha-amino acids. In this review, screening methods to obtain novel TAs,
      their biological function, biochemical characterisation and preparative
      biotransformations with TAs are described.

PMID- 20683719
TI  - Photoinactivation effects of hematoporphyrin monomethyl ether on Gram-positive
      and -negative bacteria detected by atomic force microscopy.
AB  - The photodynamic antimicrobial chemotherapy as a promising approach for
      efficiently killing pathogenic microbes is attracting increasing interest. In
      this study, the cytotoxic and phototoxic effects of hematoporphyrin monomethyl
      ether (HMME) on the Gram-positive and Gram-negative bacteria were investigated.
      The cell viability was assessed by colony-forming unit method, and the results
      indicated that there was no significant cytotoxicity but high phototoxicity in
      the examined concentrations. Notably, the Gram-positive bacteria were more
      sensitive to HMME in phototoxicity. Simultaneously, an atomic force microscope
      (AFM) was used to detect the changes in morphological and nanomechanical
      properties of bacteria before and after HMME treatment. AFM images indicate that
      upon photoinactivation, the bacterial surface changed from a smooth, homogeneous
      architecture to a heterogenous, crackled morphology. The force spectroscopy
      measurements reveal that the cell wall became less rigid and the Young's modulus
      decreased about 50%, whereas the tip-cell-surface adhesion forces increased
      significantly compared to those of native cells. It was speculated that the
      photodynamic effects of HMME induced the changes in the chemical composition of
      the outer membrane and exposure of some proteins inside the envelope. AFM can be
      utilized as a powerful and sensitive method for studying the interaction between
      bacteria and drugs.

PMID- 20683720
TI  - A new esterase EstD2 isolated from plant rhizosphere soil metagenome.
AB  - Soil metagenome constitutes a reservoir for discovering novel enzymes from the
      unculturable microbial diversity. From three plant rhizosphere metagenomic
      libraries comprising a total of 142,900 members of recombinant plasmids, we
      obtained 14 recombinant fosmids that exhibited lipolytic activity. A selected
      recombinant plasmid, pFLP-2, which showed maximum lipolytic activity, was further
      analyzed. DNA sequence analysis of the subclone in pUC119, pELP-2, revealed an
      open reading frame of 1,191 bp encoding a 397-amino-acid protein. Purified EstD2
      exhibited maximum enzymatic activity towards p-nitrophenyl butyrate, indicating
      that it is an esterase. Purified EstD2 showed optimal activity at 35  degrees C
      and at pH 8.0. The K(m) and K(cat) values were determined to be 79.4 MUM and
      120.5/s, respectively. The esterase exhibited an increase in enzymatic activity
      in the presence of 15% butanol and 15% methanol. Phylogenetic analysis revealed
      that the lipolytic protein EstD2 may be a member of a novel family of lipolytic
      enzymes. Several hypothetical protein homologs of EstD2 were found in the
      database. A hypothetical protein from Phenylobacterium zucineum HLK1, a close
      homolog of EstD2, displayed lipolytic activity when the corresponding gene was
      expressed in Escherichia coli. Our results suggest that the other hypothetical
      protein homologs of EstD2 might also be members of this novel family.

PMID- 20683721
TI  - Influence of vessel size and tortuosity on in-stent restenosis after stent
      implantation in the vertebral artery ostium.
AB  - PURPOSE: Percutaneous transluminal angioplasty and stenting is emerging as an
      alternative for treating atherosclerotic stenosis in the vertebral artery ostium.
      However, in-stent restenosis (ISR) still remains a critical issue to be
      addressed. Little is known about the relationship between anatomic
      characteristics of the artery and ISR after stent implantation. In this study, we
      have evaluated influential factors for ISR in a cohort of the patients with
      stenting in the vertebral artery ostium. METHODS: Sixty-one patients with 63
      symptomatic lesions in vertebral artery ostium treated with stenting were
      enrolled onto this study. An average of 12.5 months' clinical and angiographic
      follow-up results were analyzed retrospectively. The possible influential factors
      for ISR, including conventional risk factors of cerebrovascular diseases and
      morphological characteristics of target lesions, were evaluated by univariate and
      multivariate regression analysis. RESULTS: Technical success was achieved in all
      63 interventional procedures. Stenosis was reduced from (mean+/-standard
      deviation) 75.5+/-12% before to 1+/-3.6% after the procedure. During the mean
      12.5-month angiographic follow-up, ISR was detected in 17 treated vessels
      (27.0%), with 2 treated arteries (3.2%) resulting in occlusion, and a stent
      fracture in 1 case (1.6%). Multivariate Cox regression analysis showed that the
      tortuosity of V1 (hazard ratio 3.54, P=0.01) and smaller diameter of the stent
      (hazard ratio 3.8, P=0.04) were independent predictors of ISR. CONCLUSIONS:
      Angioplasty and stenting for symptomatic stenosis in the vertebral artery ostium
      stenosis seem to be feasible and effective. Tortuosity and smaller diameter may
      affect ISR after stent implantation.

PMID- 20683723
TI  - Identification of species in tribe Brassiceae by dot-blot hybridization using
      species-specific ITS1 probes.
AB  - Simple, reliable methods for identification of species are required for
      management of many species and lines in a plant gene bank. Species-specific
      probes were designed from published sequences of the ITS1 region in rDNA of 16
      species in Brassica and its related genera, and used as probes for dot-blot
      hybridization with plant genomic DNA. All the probes detected species-specific
      signals at dot-blots of genomic DNAs of the 16 species in Brassica, Diplotaxis,
      Eruca, and Raphanus. Signals of the Brassica digenomic species in the U's
      triangle, i.e., B. napus, B. juncea, and B. carinata, were detected by the probes
      of their parental monogenomic species, i.e., B. rapa, B. nigra, and B. oleracea.
      The probe for B. oleracea showed signals of B. balearica, B. cretica, B. incana,
      B. insularis, and B. macrocarpa, which have the C genome as B. oleracea. Eruca
      vesicaria DNA was detected by the probe for E. sativa, which has been classified
      as a subspecies of E. vescaria. DNA of leaf tissue extracted by an alkaline
      solution and seed DNA prepared by the NaI method can be used directly for dot
      blotting. Misidentification of species was revealed in 20 accessions in the
      Tohoku University Brassica Seed Bank. These results indicate dot-blot
      hybridization to be a simple and efficient technique for identification of plant
      species in a gene bank.

PMID- 20683722
TI  - Treatment planning and volumetric response assessment for Yttrium-90
      radioembolization: semiautomated determination of liver volume and volume of
      tumor necrosis in patients with hepatic malignancy.
AB  - PURPOSE: The primary purpose of this study was to demonstrate
      intraobserver/interobserver reproducibility for novel semiautomated measurements
      of hepatic volume used for Yttrium-90 dose calculations as well as whole-liver
      and necrotic-liver (hypodense/nonenhancing) tumor volume after radioembolization.
      The secondary aim was to provide initial comparisons of tumor volumetric
      measurements with linear measurements, as defined by Response Evaluation Criteria
      in Solid Tumors criteria, and survival outcomes. METHODS: Between 2006 and 2009,
      23 consecutive radioembolization procedures were performed for 14 cases of
      hepatocellular carcinoma and 9 cases of hepatic metastases. Baseline and follow
      up computed tomography obtained 1 month after treatment were retrospectively
      analyzed. Three observers measured liver, whole-tumor, and tumor-necrosis volumes
      twice using semiautomated software. RESULTS: Good intraobserver/interobserver
      reproducibility was demonstrated (intraclass correlation [ICC] > 0.9) for tumor
      and liver volumes. Semiautomated measurements of liver volumes were statistically
      similar to those obtained with manual tracing (ICC = 0.868), but they required
      significantly less time to perform (p < 0.0001, ICC = 0.088). There was a
      positive association between change in linear tumor measurements and whole-tumor
      volume (p < 0.0001). However, linear measurements did not correlate with volume
      of necrosis (p > 0.05). Dose, change in tumor diameters, tumor volume, and
      necrotic volume did not correlate with survival (p > 0.05 in all instances).
      However, Kaplan-Meier curves suggest that a >10% increase in necrotic volume
      correlated with survival (p = 0.0472). CONCLUSION: Semiautomated volumetric
      analysis of liver, whole-tumor, and tumor-necrosis volume can be performed with
      good intraobserver/interobserver reproducibility. In this small retrospective
      study, measurements of tumor necrosis were suggested to correlate with survival.

PMID- 20683725
TI  - Inappropriate shock delivery by implantable cardioverter defibrillator due to
      electrical leak from bathroom tap.

PMID- 20683726
TI  - Simultaneous injuries to both eyes in traffic accidents.
AB  - BACKGROUND: In traffic accidents, eye injuries occur as isolated or with
      polytrauma. They may involve just one eye, but simultaneous injuries to both eyes
      do happen occasionally. The aim of our paper was to reveal the risk factors, in
      an effort to reduce the number of such accidents and to prevent bilateral ocular
      damage. METHODS: All patients hospitalized at the Clinic of Eye Diseases,
      Clinical Center of Serbia, Belgrade, due to traffic accidents with bilateral eye
      injuries in a period of 9 years from the beginning of 2000 to the end of 2008
      were analyzed. RESULTS: In this 9-year period, a total of 36 patients were
      hospitalized and treated for bilateral ocular injury (72 eyes). There were 23
      males among them, the male-female ratio being 1.8:1. Mean age was 33.9 years. The
      occupations of injured persons were the following: the most common were workers-
      15, followed by clerks--seven, while less common were pupils, students,
      pensioners and housewives-three of each of them, and farmers--two. Front-seat
      passengers were the most common among the injured--20 (55.6%), then drivers--15
      (41.7%), with only one passenger from the back seat on the right side (2.7%). As
      many as 33 (91.7%) of them failed to fasten their seat belts, while 18 (50.0%)
      were drunk. Penetrating bulbar injuries or eyeball ruptures were predominant-
      66.7%, while blunt injuries were found in only two (2.8%) eyes in one single
      person; but in 22 cases (30.5%) there was adnexal damage, too. Visual acuity at
      discharge and subsequent controls was as follows: amaurosis in 21 (29.2%), less
      than 0.3 in nine (5.6%), 0.4 and better in 42 (58.1%), and normal visual acuity
      of 1.0 in 28 patients (38.3%). CONCLUSION: The major risk factors for getting
      bilateral eye injuries in traffic accidents proved to be: sitting in the front
      car seats, not fastening the seat belt and alcohol intoxication. Prevention of
      these risk factors would result in a decrease in such a large number of bilateral
      eye injuries.

PMID- 20683727
TI  - Measuring macromolecular diffusion using heteronuclear multiple-quantum pulsed
      field-gradient NMR.
AB  - We have previously shown that (1)H pulsed-field-gradient(PFG) NMR spectroscopy
      provides a facile method for monitoring proteinself-association and can be used,
      albeit with some caveats, to measure theapparent molecular mass of the diffusant
      [Dingley et al. (1995) J. Biomol.NMR, 6, 321-328]. In this paper we show that,
      for(15)N-labelled proteins, selection of(1)H-(15)N multiple-quantum (MQ)
      coherences in PFGdiffusion experiments provides several advantages over
      monitoring(1)H single-quantum (SQ) magnetization. First, the use of agradient
      selected MQ filter provides a convenient means of suppressingresonances from both
      the solvent and unlabelled solutes. Second,(1)H-(15)N zero-quantum coherence
      dephases morerapidly than (1)H SQ coherence under the influence of a PFG.This
      allows the diffusion coefficients of larger proteins to be measuredmore readily.
      Alternatively, the gradient length and/or the diffusion delaymay be decreased,
      thereby reducing signal losses from relaxation. In orderto extend the size of
      macromolecules to which these experiments can beapplied, we have developed a new
      MQ PFG diffusion experiment in which themagnetization is stored as longitudinal
      two-spin order for most of thediffusion period, thus minimizing sensitivity
      losses due to transverserelaxation and J-coupling evolution.

PMID- 20683728
TI  - Plant NAC-type transcription factor proteins contain a NARD domain for repression
      of transcriptional activation.
AB  - Plant-specific transcription factor NAC proteins play essential roles in many
      biological processes such as development, senescence, morphogenesis, and stress
      signal transduction pathways. In the NAC family, some members function as
      transcription activators while others act as repressors. In the present study we
      found that though the full-length GmNAC20 from soybean did not have
      transcriptional activation activity, the carboxy-terminal activation domain of
      GmNAC20 had high transcriptional activation activity in the yeast assay system.
      Deletion experiments revealed an active repression domain with 35 amino acids,
      named NARD (NAC Repression Domain), in the d subdomain of NAC DNA-binding domain.
      NARD can reduce the transcriptional activation ability of diverse transcription
      factors when fused to either the amino-terminal or the carboxy-terminal of the
      transcription factors. NARD-like sequences are also present in other NAC family
      members and they are functional repression domain when fused to VP16 in plant
      protoplast assay system. Mutation analysis of conserved amino acid residues in
      NARD showed that the hydrophobic LVFY motif may partially contribute to the
      repression function. It is hypothesized that the interactions between the
      repression domain NARD and the carboxy-terminal activation domain may finally
      determine the ability of NAC family proteins to regulate downstream gene
      expressions.

PMID- 20683729
TI  - Genomic profiling of cell-free DNA in blood and bone marrow of prostate cancer
      patients.
AB  - PURPOSE: To advance the characterization of tumor-associated cell-free DNA in
      blood and bone marrow (BM), a rapid profiling method using methylation-specific
      multiplex ligation-dependent probe amplification (MS-MLPA) was established. MS
      MLPA detects genetic and epigenetic aberrations of 37 tumor suppressor genes
      (TSG) in a single reaction and might, therefore, avoid the cumbersome single gene
      analyses. METHODS: The validity of MS-MLPA for using cell-free plasma DNA was
      assessed by analyzing blood and BM samples of 91 patients with prostate cancer.
      As reference analyses, the methylation patterns of 4 genes (CD44, E-cadherin,
      CDKN2A and PTEN) chosen from the TSG set of the MS-MLPA kit were investigated in
      single reactions by sodium bisulfite DNA sequencing. RESULTS: Copy number changes
      and aberrant DNA methylation of 37 circulating TSG could be analyzed in BM and
      blood of 30 and 13 of the 91 patients, respectively, whereas the DNA content in
      the remaining samples was too low (<50 ng/MUl of eluted DNA). The copy number of
      28 of the 37 TSG was altered, and most changes were found for APC, CHFR, TP73 and
      GSTP1 genes in BM plasma. Statistical evaluations showed an association between
      copy number changes of TP73 and a positive resection margin of the prostate (p =
      0.05). Both MS-MLPA and sodium bisulfite sequencing techniques showed that all
      genes were unmethylated. CONCLUSIONS: Our results demonstrate the potential and
      limitation of MS-MLPA for multiplex characterization of TSG in cell-free plasma
      DNA as a new non-invasive approach to obtain information on the molecular tumor
      biology of individual cancer patients.

PMID- 20683730
TI  - Dynamics of the association between a long-lived understory myrmecophyte and its
      specific associated ants.
AB  - Myrmecophytic symbioses are widespread in tropical ecosystems and their diversity
      makes them useful tools for understanding the origin and evolution of mutualisms.
      Obligate ant-plants, or myrmecophytes, provide a nesting place, and, often, food
      to a limited number of plant-ant species. In exchange, plant-ants protect their
      host plants from herbivores, competitors and pathogens, and can provide them with
      nutrients. Although most studies to date have highlighted a similar global
      pattern of interactions in these systems, little is known about the temporal
      structuring and dynamics of most of these associations. In this study we focused
      on the association between the understory myrmecophyte Hirtella physophora
      (Chrysobalanaceae) and its obligate ant partner Allomerus decemarticulatus
      (Myrmicinae). An examination of the life histories and growth rates of both
      partners demonstrated that this plant species has a much longer lifespan (up to
      about 350 years) than its associated ant colonies (up to about 21 years). The
      size of the ant colonies and their reproductive success were strongly limited by
      the available nesting space provided by the host plants. Moreover, the resident
      ants positively affected the vegetative growth of their host plant, but had a
      negative effect on its reproduction by reducing the number of flowers and fruits
      by more than 50%. Altogether our results are important to understanding the
      evolutionary dynamics of ant-plant symbioses. The highly specialized interaction
      between long-lived plants and ants with a shorter lifespan produces an asymmetry
      in the evolutionary rates of the interaction which, in return, can affect the
      degree to which the interests of the two partners converge.

PMID- 20683731
TI  - Strontium isotope analyses of large herbivore habitat use in the Cape Fynbos
      region of South Africa.
AB  - The Cape Fynbos region of South Africa, a global biodiversity hotspot, hosted a
      diverse large mammal fauna till shortly after permanent European settlement
      (1652). How these animals survived in this exceptionally nutrient-poor
      environment is puzzling and it is generally believed that they restricted their
      movements to the more fertile shale areas. We tested the hypothesis that large
      herbivores avoid nutrient-poor limestone and sandstone fynbos shrublands in
      favour of shale-derived renosterveld vegetation using strontium (Sr) isotope
      analysis. If this technique could reconstruct the preferred feeding habitats of
      the contemporary fauna, it might also be useful for reconstructing the preferred
      feeding grounds of an extinct fauna. Using the assumption that small rodents have
      spatially restricted foraging activities, we determined the (87)Sr/(86)Sr isotope
      ratios of rodent teeth to establish the isotopic signal characteristic of the
      different geological substrates in the area. We then analysed (87)Sr/(86)Sr
      isotope ratios in the bones of a number of different large herbivores found in De
      Hoop Nature Reserve using laser ablation multi-collector inductively coupled
      plasma mass spectrometry. These values were compared to the bioavailable (rodent)
      values on the respective geological substrates. The technique identified
      differences in feeding substrate selection between different species and groups
      of the same species. The results also showed that shale renosterveld shrubland is
      not the exclusive source of nutrition for the large herbivores. Strikingly
      different isotope ratios among individuals in some populations pointed to
      significant dispersal events from distant sources. However, we were unable to
      pinpoint the exact feeding areas using Sr isotope analysis probably because some
      animals use a combination of substrates for feeding and because the geology of
      the study area is complex with graded isotope signals. We suggest that this
      technique is a valuable additional tool for exploring large mammal foraging
      behaviour on habitats associated with contrasting and less complex geology.

PMID- 20683732
TI  - [Chronic pain in German medical practices. Current demands placed on the primary
      health care system due to pain prevalence].
AB  - BACKGROUND: The prevalence of chronic pain as related to the supply situation in
      primary care has been investigated insufficiently. PATIENTS AND METHODS: A
      questionnaire was used to collect data of 1,201 patients in 6 different
      specialists' practices (general medicine, surgery, internal medicine, neurology,
      oncology, orthopaedics). The questions posed related to socio-demographic facts,
      pain characteristics, psychosocial effects, previous therapies and their
      subjective effectiveness. RESULTS: Pain was the reason for consulting a doctor in
      nearly 50% of the patients; 40% of all respondents complained about chronic pain,
      defined as recurrent or constant pain lasting longer than 6 months. As many as
      90% of these subjects reported psychosocial impairment due to chronic pain and
      25% evaluated their therapies as ineffective. CONCLUSION: Chronic pain is a major
      problem in primary care. The high level of suffering and the enormous
      socioeconomic impact on public health demand consequences. Improvements in
      undergraduate and postgraduate training are urgently required for both an
      adequate pain treatment and the prevention of chronic pain.

PMID- 20683733
TI  - Effect of mild and moderate hypothermia on hypoxic injury in nearly pure neuronal
      culture.
AB  - PURPOSE: The effects of mild and moderate hypothermic therapy on cerebral injury
      are still controversial. Our hypothesis is that mild and moderate hypothermia
      should have some effects on neurons themselves if they really have protective
      effects. By using a nearly pure neuronal culture, we evaluated the effects and
      mechanism of hypothermia against hypoxic insult. METHODS: A nearly pure neuronal
      culture from cortices of 18-day-old Wister rats was used. The neurons were
      exposed to below 1% oxygen at 3 different temperatures (30, 33 and 37 degrees C).
      First, cell viability was measured by assessing viable neurons with trypan blue.
      Second, to evaluate the mechanism, the extracellular glutamate concentration was
      measured by high-performance liquid chromatography after hypoxia; cell viability
      after exposure to extrinsic glutamate was also evaluated. Next, mitochondrial
      membrane potential was estimated, by monitoring aggregation of MitoCaptureTM, and
      the percentage of apoptotic cells was evaluated by staining with Hoechst 33342
      and propidium iodide. RESULTS: After 24-h hypoxic insult, cell viability at 30
      and 33 degrees C was significantly higher than at 37 degrees C. There was no
      significant difference between extracellular concentrations of glutamate after
      hypoxia or cell viability after glutamate exposure among the 3 temperature
      groups. In moderate hypothermia, the number of neurons with mitochondrial injury
      and the percentage of apoptotic cells were significantly reduced. CONCLUSION:
      Mild and moderate hypothermia inhibited hypoxic neuronal cell death. The
      mechanism of this effect may be related to protection of mitochondrial function,
      presumably followed by inhibition of apoptosis, at least in moderate hypothermia.

PMID- 20683734
TI  - No explicit memory after skin incision without anesthetic except for remifentanil
      infusion.

PMID- 20683735
TI  - Paradoxical carbon dioxide embolism during endoscopic thyroidectomy confirmed by
      transesophageal echocardiography.
AB  - Carbon dioxide (CO2) embolism is a rare but potentially life-threatening
      complication of laparoscopic procedures. Although endoscopic thyroidectomy using
      CO2 gas insufflation appears to be superior to conventional open thyroidectomy in
      terms of cosmetic results, it may cause venous or fatal paradoxical CO2 embolism.
      We report a case of paradoxical CO2 embolism during CO2 gas insufflation in an
      endoscopic thyroidectomy that was confirmed by transesophageal echocardiography
      (TEE). Paradoxical embolization via transpulmonary right-to-left shunting of
      venous CO2 gas emboli was revealed by TEE examination. The patient recovered
      without complications. In conclusion, although endoscopic thyroidectomy is a
      promising approach that is gaining popularity and offers excellent cosmetic
      results compared with conventional open thyroidectomy, this case report
      emphasizes the importance of anticipating and being vigilant for potential CO2
      embolism.

PMID- 20683736
TI  - Back massage therapy promotes psychological relaxation and an increase in
      salivary chromogranin A release.
AB  - Massage therapy promotes psychosocial relaxation, reduces stress and has been
      reported to improve the immune function. As such, massage therapy is currently
      used in palliative care for the relief of anxiety and pain. Although psychosocial
      status has been evaluated using subjective psychological tests, such as State
      Trait Anxiety Inventory (STAI), subjective psychological tests are of limited
      value if the subjects fail to report reliably. Salivary biomarkers have been
      recently suggested as useful objective markers for assessing psychosocial status.
      To determine whether salivary biomarkers are useful objective indices for
      assessing the effects of back massage on the mental status of 25 young healthy
      female volunteers, we measured heart rate and salivary biomarkers (alpha-amylase
      activity, cortisol, and chromogranin A) and assessed the STAI score before and
      after the back massage. Back massage significantly reduced the heart rate and
      STAI; however, salivary amylase and cortisol levels did not change. In contrast,
      the level of salivary chromogranin A significantly increased. We therefore
      conclude that changes in the salivary biomarkers tested here may not indicate
      changes in psychological status following massage therapy. However, the increase
      in chromogranin A release may contribute to the immunologically beneficial
      effects of massage therapy as chromogranin A has antibacterial and antifungal
      activity.

PMID- 20683737
TI  - 100 years poliovirus: from discovery to eradication. A meeting report.
AB  - Just over hundred years ago, Karl Landsteiner and Erwin Popper identified a
      virus, later termed poliovirus, as the causative agent of poliomyelitis. This
      groundbreaking discovery simultaneously provided the basis for the measures that
      today prevent the outbreaks of the terrible epidemics caused by poliovirus. In
      1988, the WHO started its eradication program to eliminate the virus from the
      planet. The symposium celebrated the discovery of poliovirus and discussed our
      current state of knowledge of poliovirus biology. Prospects for the eradication
      program were evaluated, with particular emphasis being placed on why certain
      countries still have not succeeding in interrupting wild-type transmission of
      poliovirus. Discussion also centred on the role of inactivated poliovirus
      vaccines in the eradication program and the maintenance of a poliovirus-free
      world, whenever this goal should be achieved.

PMID- 20683738
TI  - Extended dosing of etanercept 25 mg can be effective in patients with ankylosing
      spondylitis: a retrospective analysis.
AB  - As a measure of healthcare cost containment, the total number of vials of
      entanercept (25 mg) that can be prescribed for patients with inflammatory
      arthritis is restricted in Korea. Consequently, attempts to extend the dosing
      interval while maintaining the efficacy have not been an uncommon clinical
      practice. The aim of this study was to determine if extended doing interval of
      etanercept can be effective in patients with ankylosing spondylitis (AS). We
      performed a retrospective analysis using medical records at a single tertiary
      hospital. One hundred and nine patients with AS and 79 patients with rheumatoid
      arthritis (RA) started on etanercept between November 2004 and November 2009 were
      identified. Etanercept (25 mg) was started with twice-weekly dosing schedule.
      Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), C-reactive protein
      (CRP), and etanercept dosing interval for AS patients at 0, 3, 9, 15, 21 months
      were reviewed. Dosing interval for RA patients was analyzed for comparison. In
      AS, mean dosing interval was 4.7 +/- 2.1 days at 3 months and was increased to
      12.1 +/- 7.0 days at 21 months. Despite the progressive increase in the dosing
      interval, the mean BASDAI declined rapidly at 3 months, and continued to decrease
      over 21 months. Mean CRP declined after 3 months of therapy and remained low
      thereafter. In RA, mean dosing interval was 4.0 +/- 1.2 days at 3 months and 5.1
      +/- 1.8 days at 21 months. In conclusion, in AS, extended dosing of etanercept
      can be effective without compromising clinical and laboratory markers of disease
      activity as measured by BASDAI and CRP, respectively. Tapering of etanercept was
      less accommodating in RA when compared to AS.

PMID- 20683739
TI  - Treating early rheumatoid arthritis intensively: current UK practice does not
      reflect guidelines.
AB  - Recent guidance published in the UK by the National Institute for Health and
      Clinical Excellence has recommended that patients with early rheumatoid arthritis
      (RA) are treated with combination disease-modifying anti-rheumatic drugs
      (DMARDs). It is unclear to what extent this reflects current UK practice. UK
      rheumatologists were asked to complete a web-based questionnaire asking about
      their treatment preferences in early RA and to indicate their attitudes to
      combination DMARD therapy. Although the majority was using step-up combination
      DMARDs, only 50% of the 258 respondents were using initial combination therapy in
      any patients with newly diagnosed RA despite scoring it highly for efficacy and
      safety. Concerns were expressed about side effects, increased monitoring
      requirements, and acceptability to patients. Current UK practice does not reflect
      the recently published guidelines. Uncertainties remain as to which patients need
      combination therapy and the optimal regimes to use. Further research is required
      to elucidate attitudes to aggressive therapy in early disease.

PMID- 20683740
TI  - Autoantibodies for gastrointestinal organ-specific autoimmune diseases in
      rheumatoid arthritis patients and their relatives.
AB  - BACKGROUND: Clustering of autoimmune diseases is common and may be due to genetic
      background and exposition to environmental triggers. OBJECTIVE: The aim is to
      carry out a laboratory and clinical study of the prevalence of gastrointestinal
      organ-specific autoantibodies in rheumatoid arthritis (RA) patients and their
      relatives. METHODS: Serum samples of 156 RA patients, 200 relatives, and 100
      healthy controls were studied for anti-smooth muscle antibody (ASMA), anti
      mitochondrial (AMA), anti-parietal cell (APCA), anti-liver-kidney microsome
      (LKM), and anti-endomysium antibodies (IgA-EmA) by indirect immunofluorescence.
      RESULTS: A total of eight out of the 156 (5.1%) RA patients were positive for the
      autoantibodies (ASMA = 1; AMA = 2, APCA = 5). In the relative group, 12/200 (6%)
      had at least one positive autoantibody (ASMA = 1; AMA = 2, APCA = 7, IgA-EmA =
      2). In the control group, two out of the 100 (2%) healthy controls were positive
      (ASMA = 1, APCA = 1). No statistical difference was found between RA patients,
      their relatives, and controls in relation to the frequency of autoantibodies
      evaluated. CONCLUSION: Although RA patients and their relatives have positivity
      of AMA, ASMA, and APCA without statistical difference in relation to healthy
      individuals, the findings may be of value for adequate clinical approach of these
      subjects.

PMID- 20683741
TI  - Total elbow arthroplasty: history, current concepts, and future.
AB  - Total elbow arthroplasty (TEA) has proven to be a reliable joint replacement
      procedure that has a high degree of patient satisfaction. The long-term
      functional and implant survival scores rival those of total knee arthroplasty.
      Despite these favorable outcomes, few patients with disabling elbow degenerative
      conditions have TEA recommended to them as an alternative procedure by
      rheumatologists, physiatrists, or orthopedists. This article reviews the history,
      current concepts, and future of TEA.

PMID- 20683742
TI  - Performance of global assessments of hip, knee, and back symptom change.
AB  - The objective of this study is to compare patients' global assessments of change
      in knee, hip, and back symptoms with actual changes over time in pain, function,
      and radiographic severity. The participants (n = 894, 80% female, mean age = 66
      years) completed two assessments (mean of 4 years apart) as part of a study on
      the genetics of generalized osteoarthritis. At both assessments, participants
      completed the Western Ontario and McMaster Universities OA Index (WOMAC), and
      radiographic severity was assessed for knees, hips, and low back. At the second
      assessment, participants described changes in knee, hip, and low back symptoms as
      worse, better, same, or never had symptoms. Analysis of covariance models
      examined mean changes in WOMAC scores and radiographic severity according to
      categories of the global assessment measures. Statistical significance was
      examined for linear trend. Mean WOMAC total, pain, and function scores decreased
      (indicating improvement) among participants who indicated joint symptoms were
      better, showed little change among those who reported symptoms were the
      same/never had symptoms, and increased among those who reported symptoms were
      worse. For all analyses except the comparison of WOMAC pain change according to
      global assessment of low back symptom change, there was a statistically
      significant linear trend (p < 0.05). Patterns were similar for changes in
      radiographic severity, but the tests of linear trend were not statistically
      significant. Results support the concordance of these global assessments of joint
      symptom change with actual changes in self-reported symptoms. These global
      assessments may be useful for assessing change over time when baseline data are
      unavailable.

PMID- 20683743
TI  - Colonic cancer in a patient with intestinal malrotation: a case report.
AB  - We present a case of a 76-year-old patient with intestinal malrotation, with
      incomplete rotation of the small intestine and abnormal positioning of the
      duodenum and superior mesenteric vessels over the transverse colon. Furthermore,
      the patient suffered of a concomitant cancer of the ascending colon.

PMID- 20683744
TI  - Current management of diverticular disease of the colon.
AB  - The medical treatment plays the first role in the vast majority of cases. Severe
      acute diverticulitis requires hospitalization and supporting care with
      intravenous fluids and antibiotics such as ciprofloxacin and metronidazole.
      Emergency operative intervention is necessary if complication occurs.
      Laparoscopic surgery has a well-defined place and such colectomy has been
      gaining, nowadays, more popularity.

PMID- 20683745
TI  - Loop stomas with a subcutaneously placed bridge device.
AB  - AIM: To describe and evaluate a new technique for supporting a loop stoma with a
      simple removable subcutaneous bridge device. METHODS: Fifty-five patients
      underwent a procedure resulting in a loop stoma. Thirty patients had a loop
      colostomy and twenty-five a loop ileostomy. In all cases, the stoma was supported
      with a removable subcutaneous redivac drain fixed to the skin. RESULTS: There was
      no incidence of mechanical obstruction, stenosis, retraction, mucosal erosion or
      subcutaneous infection. Daily cleaning and care of the stoma was very simple, and
      the removal of the bridge device was carried out without opening the collecting
      bag. CONCLUSION: Our proposed technique is safe and feasible without considerable
      complications.

PMID- 20683746
TI  - Brain metastases in colorectal cancer.
AB  - AIM: The aim of this study is the presentation of brain secondaries associated
      with colorectal cancer. PATIENTS AND METHODS: In the period between 1990 and
      2009, 670 patients with colorectal cancer were treated. RESULTS: From 670
      patients, 5 patients were identified with brain metastases. The incidence was
      0.73%. The median interval between the colorectal cancer and the development of
      the brain secondaries was 7.5 months. Median survival after the diagnosis of
      brain metastases was 4.3 months. CONCLUSION: Brain metastases associated with
      colorectal cancer are relatively rare, but also a frequent cause of death.

PMID- 20683747
TI  - Sacral neuromodulation for the treatment of faecal incontinence in a patient with
      organophosphate poisoning.
AB  - Faecal incontinence is a debilitating condition. Sacral neuromodulation may have
      a role in the treatment of faecal incontinence. We report a case of faecal
      incontinence secondary to chronic organophosphate poisoning, which was
      successfully treated with sacral neuromodulation. The patient's faecal
      incontinence and quality of life improved significantly.

PMID- 20683748
TI  - Large bowel obstruction due to endometriosis.
AB  - We report on three cases of premenopausal female patients with large bowel
      endometriosis causing intermittent obstruction.

PMID- 20683749
TI  - Retractile mesenteritis appearing as a sigmoid colon tumor.
AB  - Retractile mesenteritis is a rare, fibrosing, inflammatory disease affecting the
      adipose tissue of the intestinal and colonic mesentery. So far, about 300 cases
      have been reported in the literature. We present a case of retractile
      mesenteritis.

PMID- 20683750
TI  - Pudendal nerve block versus local anesthesia for harmonic scalpel
      hemorrhoidectomy: a prospective randomized study.
AB  - BACKGROUND: This prospective randomized trial was used to compare two different
      local anesthetic techniques, local perianal anesthesia and pudendal nerve block,
      used for harmonic scalpel hemorrhoidectomy (HSH). METHODS: A total of 120
      patients with grade III or IV hemorrhoids were randomly chosen to perform HSH (60
      patients under local anesthesia--Group A and 60 patients under pudendal nerve
      block--Group B). RESULTS: Additional perioperative analgesia during the procedure
      was needed in 37 patients of group A and 18 patients of group B (P < 0.001). A
      total of 27 patients from group A and 8 patients from group B (P < 0.001)
      required additional postoperative analgesia apart from the standard administered
      analgesics. A statistical significant difference in favor of the second group (B)
      -(P < 0.003) was found regarding the discharge point from the hospital when the
      number of patients that were able to be discharged from the hospital on the day
      of the operation and the first postoperative day was the comparison parameter.
      Group B (P < 0.001) was superior to local group regarding VAS pain score at
      discharge for the patient group that were discharge on the day of surgery (5.1
      vs. 2.2). CONCLUSION: These data suggest that HSH performed under pudendal nerve
      block is a safe and efficient technique.

PMID- 20683751
TI  - Desmoid tumor of mesentery in familial adenomatous polyposis: a case report.
AB  - Our case concerns a 52-year-old male with FAP, who was treated surgically by
      restorative colectomy and ileal pouch anal anastomosis. Three years later, he
      presented with acute epigastric pain and obstructive ileum. While a mass in the
      left lateral abdominal region was palpated. The patient underwent laparotomy,
      some adhesions were dissected and biopsies were taken from the mass. Pathological
      examination revealed a desmoid tumor of the mesentery.

PMID- 20683752
TI  - The handsewn anastomosis after colon resection due to colonic cancer.
AB  - AIM: The purpose of our study is to present the results of the handsewn single
      layer interrupted extramucosal anastomosis following colon cancer. PATIENTS AND
      METHODS: In the period between 1989 and 2009, 276 intestinal anastomoses were
      fashioned following colon resection using single-layer interrupted extramucosal
      3/0 Vicryl. RESULTS: The mean hospital stay was 8.2 days. Twenty-three patients
      had postoperative complications, and the total morbidity was 8.3%. Seven
      anastomotic leakages occurred (2.5%). The mortality rate was 2.5%. CONCLUSION:
      The single-layer anastomosis with interrupted extramucosal sutures after colon
      resection is safe and effective.

PMID- 20683753
TI  - Enhancement of colonic anastomotic strength in rats by short-chain fatty acids.
AB  - BACKGROUND: The present study is aiming at elucidating the effect of
      intraoperative lavage with short-chain fatty acids (SCFAs) on colonic anastomosis
      in rats. METHODS: Forty male Wistar rats were randomized into four groups (10
      rats each). After resection of a segment of transverse colon, an end-to-end
      anastomosis was performed. In the 1st group, no intraoperative large bowel lavage
      was performed; in the 2nd, a lavage with normal saline solution; in the 3rd, the
      animals received a diet rich in SCFAs pre- and postoperatively, and a lavage with
      normal saline was performed; and in the 4th group, an intraoperative lavage with
      SCFAs was carried out. On the 4th postoperative day, the animals were sacrificed.
      Septic complications, adhesions and anastomoses were graded macroscopically and
      histologically, and bursting pressure of the anastomoses, CRP, IL-6 and TNF-a was
      measured. RESULTS: Fewer septic complications (abscesses and minimal ruptures)
      and adhesions were observed in the 4th group with the intraoperative lavage with
      SCFAs. The bursting pressure also, in the same group, was higher (73.3 mmHg),
      followed by the 1st group (67.1 mmHg). CONCLUSION: Intraoperative lavage with
      SCFAs increases the bursting pressure of colonic anastomoses, while lavage with
      saline solution decreases it, in comparison to the group without lavage.

PMID- 20683754
TI  - Prospective clinical trial comparing sphincterotomy, nitroglycerin ointment and
      xylocaine/lactulose combination for the treatment of anal fissure.
AB  - BACKGROUND: The aim of this study is to compare the ability of three treatments
      in patients with anal fissure, sphincterotomy, nitroglycerin ointment and
      combination of gel xylocaine and lactulose. METHODS: Ninety adults divided in
      three groups of 30 patients each group, received one of the three treatments in a
      3-year interval (2007-2009) and the follow-up was for 2 months. Group A received
      nitroglycerin ointment, Group B underwent sphincterotomy and Group C received gel
      xylocaine and lactulose. RESULTS: Concerning pain, after treatment 60% of
      patients in Group A did not complain of pain, 20% had transient pain, another 10%
      moderate pain and the remaining 10% had severe pain. In Group B, 95% of the
      patients had no pain and only 5% had mild, transient pain. In Group C 60% of the
      patients had moderate pain and the other 40% suffered from severe pain.
      Concerning fissure healing, in 60% of the patients of Group A, the fissure was
      healed. In Group B fissure healed in 93.3% and in Group C only in 16.6% of the
      patients. CONCLUSION: The "gold standard" for anal fissure treatment is the
      lateral internal sphincterotomy and that each one of the three methods has its
      advantages and disadvantages.

PMID- 20683755
TI  - Circumferential stapled procedure for bleeding ano-rectal varices.
AB  - AIM: Aim of this study is to demonstrate that the circumferential stapled
      procedure for rectal varices is a feasible and suitable method of controlling
      bleeding varices. PATIENTS: Between 2004 and December 2007, four patients
      underwent the procedure as an emergency, with the intention of controlling
      haemorrhage. RESULTS: Four patients underwent this procedure, with successful
      control of bleeding achieved in all. No further rebleeding was observed in the
      follow-up period. CONCLUSION: The stapled disruption of bleeding rectal varices
      in patients with portal hypertension seems a very useful and effective procedure.

PMID- 20683757
TI  - Phase II trial of ritonavir/lopinavir in patients with progressive or recurrent
      high-grade gliomas.
AB  - Current therapies for recurrent or progressive high-grade gliomas (HGG, WHO grade
      3-4) produce a 6-month progression-free survival of only 10-25%. Migration and
      invasion by HGG is mediated in part by matrix metalloproteases (MMPs) which
      promote remodeling of the extracellular matrix. Several HIV protease inhibitors
      (HIVPI) decrease the expression of MMPs in astrocytes and microglia. Given these
      mechanisms of antitumor activity of HIVPI, we evaluated the efficacy of
      ritonavir/lopinavir, a combination HIVPI, in patients with progressive or
      recurrent HGG in an open label phase II trial. Nineteen patients were treated in
      this study. Patients received ritonavir/lopinavir (400 mg/100 mg) orally twice
      daily. All patients were treated until progression of disease or unacceptable
      toxicity. A complete response was seen in one patient (5%). Three patients (16%)
      had stable disease as the best response. Fifteen patients (79%) had progressive
      disease. The 6-month progression free survival (PFS(6)) was 11% (2 of 19
      patients). Ritonavir/lopinavir was well tolerated in patients with heavily
      pretreated refractory HGG, and no grade 3 or 4 toxicity was seen. The activity at
      the dose and schedule used in this study, however, was modest and the study did
      not meet its efficacy endpoint.

PMID- 20683759
TI  - Editorial policy in a period of rapid evolution of NMR with biological
      macromolecules.

PMID- 20683756
TI  - The significance, development and progress of high-throughput combinatorial
      histone code analysis.
AB  - The physiological state of eukaryotic DNA is chromatin. Nucleosomes, which
      consist of DNA in complex with histones, are the fundamental unit of chromatin.
      The post-translational modifications (PTMs) of histones play a critical role in
      the control of gene transcription, epigenetics and other DNA-templated processes.
      It has been known for several years that these PTMs function in concert to allow
      for the storage and transduction of highly specific signals through combinations
      of modifications. This code, the combinatorial histone code, functions much like
      a bar code or combination lock providing the potential for massive information
      content. The capacity to directly measure these combinatorial histone codes has
      mostly been laborious and challenging, thus limiting efforts often to one or two
      samples. Recently, progress has been made in determining such information
      quickly, quantitatively and sensitively. Here we review both the historical and
      recent progress toward routine and rapid combinatorial histone code analysis.

PMID- 20683760
TI  - Three-dimensional heteronuclear NMR techniques for assignment and conformational
      analysis using exchangeable protons in uniformly 13C-enriched oligosaccharides.
AB  - We present heteronuclear three-dimensional gradient-NMR techniques for the
      resonanceassignment of exchangeable (-OH and -NH) protons in uniformly 13C
      isotopically enrichedoligosaccharides and for the measurement of 1H-1H nuclear
      Overhauser enhancementsinvolving these protons. These techniques are derived from
      conventional HOHAHA-HSQCand NOESY(ROESY)-HSQC experiments, and are illustrated in
      application to a sample ofuniformly 13C-enriched Galbeta1-4GlcNAc, and
      demonstrate that a total of 35 ROEs involvingexchangeable protons can be detected
      and assigned. We present a quantitative analysis ofthese ROEs that can only be
      accommodated in a model of the solution behaviour of theoligosaccharide that
      involves considerable internal motion.

PMID- 20683758
TI  - Effects of combining low frequency ultrasound irradiation with papaverine on the
      permeability of the blood-tumor barrier.
AB  - This study was performed to determine whether low frequency ultrasound (LFU)
      irradiation, Papaverine (PA) infusion and combination LFU irradiation with PA
      infusion opened the blood-tumor barrier (BTB) by affecting tight junctions (TJ)
      associated proteins zonula occluden-1 (ZO-1), occludin and caludin-5. In a rat
      brain glioma model, we found that the mRNA and protein expression levels of ZO-1,
      occludin and claudin-5 were decreased by LFU irradiation and PA infusion. LFU
      induced and PA-induced decrease of ZO-1, occludin and claudin-5 was further
      decreased after combining LFU irradiation with PA infusion. Immunohistochemistry
      assay showed that the decreased expression of ZO-1, occludin and claudin-5 was
      the most obvious in the tumor capillaries. Meanwhile, Evans blue assay showed
      that the permeability of BTB was increased, and transmission electron microscopy
      (TEM) indicated that TJ was opened. This led to the conclusion that LFU
      irradiation and PA infusion together can open the BTB by paracellular pathway.
      Significantly down-regulated expression levels of ZO-1, occludin and claudin-5
      might be one of the molecular mechanisms of combining LFU and PA enhancing the
      permeability of BTB.

PMID- 20683761
TI  - Backbone dynamics of proteins derived from carbonyl carbon relaxation times at
      500, 600 and 800 MHz: Application to ribonuclease T1.
AB  - The backbone dynamics of uniformly 13C/15N-enriched ribonuclease T1 have
      beeninvestigated using carbonyl carbon relaxation times recorded at three
      different spectrometerfrequencies. Pulse sequences for the determination of the
      longitudinal (T1) and transverse (T2)relaxation times are presented. The
      relaxation behaviour was analysed in terms of a multispinsystem. Although the
      chemical shift anisotropy relaxation mechanism dominates at highmagnetic field
      strength, the contributions of the dipole-dipole interactions and thecross
      correlation between these two relaxation mechanisms have also been
      considered.Information about internal motions has been extracted from the
      relaxation data using themodel-free approach of Lipari and Szabo in order to
      determine order parameters (S2) andeffective internal correlation times (taui).
      Using a relatively simple relation between themeasured relaxation rates and the
      spectral density function, an analytical expression for themicrodynamical
      parameters in dependence of T1 and T2 has been derived. The spectraldensity
      mapping technique has been applied in order to study the behaviour of the
      carbonylcarbon resonances in more detail.

PMID- 20683762
TI  - Application of multiple-quantum line narrowing with simultaneous 1H and 13C
      constant-time scalar-coupling evolution in PFG-HACANH and PFG-HACA(CO)NH triple
      resonance experiments.
AB  - Many triple-resonance experiments make use of one-bond heteronuclear scalar
      couplings toestablish connectivities among backbone and/or side-chain nuclei. In
      medium-sized(15-30 kDa) proteins, short transverse relaxation times of Calpha
      single-quantum stateslimit signal-to-noise (S/N) ratios. These relaxation
      properties can be improved usingheteronuclear multiple-quantum coherences (HMQCs)
      instead of heteronuclear single-quantumcoherences (HSQCs) in the pulse sequence
      design. In slowly tumbling macromolecules, theseHMQCs can exhibit significantly
      better transverse relaxation properties than HSQCs.However, HMQC-type experiments
      also exhibit resonance splittings due to multiple two- andthree-bond homo- and
      heteronuclear scalar couplings. We describe here a family of pulsed-field
      gradient (PFG) HMQC-type triple-resonance experiments using simultaneous 1H
      and13C constant-time (CT) periods to eliminate the t1 dependence of these scalar
      couplingeffects. These simultaneous CT PFG-(HA)CANH and PFG-(HA)CA(CO)NH HMQC
      typeexperiments exhibit sharper resonance line widths and often have better S/N
      ratios than thecorresponding HSQC-type experiments. Results on proteins ranging
      in size from 6 to 30 kDashow average methine CalphaH HMQC:HSQC enhancement
      factors of 1.10 +/- 0.15, withabout 40% of the cross peaks exhibiting better S/N
      ratios in the simultaneous CT-HMQCversions compared with the HSQC versions.

PMID- 20683763
TI  - Evaluation of hexose and pentose in pre-cultivation of Candida guilliermondii on
      the key enzymes for xylitol production in sugarcane hemicellulosic hydrolysate.
AB  - The evaluation of hexose and pentose in pre-cultivation of Candida guilliermondii
      FTI 20037 yeast on xylose reductase (XR) and xylitol dehydrogenase (XDH) enzymes
      activities was performed during fermentation in sugarcane bagasse hemicellulosic
      hydrolysate. The xylitol production was evaluated by using cells previously
      growth in 30.0 gl(-1) xylose, 30.0 gl(-1) glucose and in both sugars mixture
      (30.0 gl(-1) xylose and 2.0 gl(-1) glucose). The vacuum evaporated hydrolysate
      (80 gl(-1)) was detoxificated by ion exchange resin (A-860S; A500PS and C-150
      Purolite(r)). The total phenolic compounds and acetic acid were 93.0 and 64.9%,
      respectively, removed by the resin hydrolysate treatment. All experiments were
      carried out in Erlenmeyer flasks at 200 rpm, 30 degrees C. The maximum XR (0.618
      Umg (Prot) (-1)) and XDH (0.783 Umg (Prot) (-1)) enzymes activities was obtained
      using inoculum previously growth in both sugars mixture. The highest cell
      concentration (10.6 gl(-1)) was obtained with inoculum pre-cultivated in the
      glucose. However, the xylitol yield and xylitol volumetric productivity were
      favored using the xylose as carbon source. In this case, it was observed maximum
      xylose (81%) and acetic acid (100%) consumption. It is very important to point
      out that maximum enzymatic activities were obtained when the mixture of sugars
      was used as carbon source of inoculum, while the highest fermentative parameters
      were obtained when xylose was used.

PMID- 20683764
TI  - Evaluation of tertiary treatment by fungi, enzymatic and photo-Fenton oxidation
      on the removal of phenols from a kraft pulp mill effluent: a comparative study.
AB  - Pulp and paper mills generate pollutants associated to their effluents depending
      upon the type of process, type of the wood materials, process technology applied,
      management practices, internal recirculation of the effluent for recovery, the
      amount of water used in the industrial process and type of secondary treatment.
      This study is the first that reports a simultaneous evaluation of the effects of
      tertiary treatments by fungi (Rhizopus oryzae and Pleurotus sajor caju), by
      enzyme (laccase) and by an oxidation process (photo-Fenton) on individual phenols
      (vanillin, guaiacol, phloroglucinol, vanillic acid and syringic acid) of a
      Eucalyptus globulus bleached kraft pulp and paper mill final effluent after
      secondary treatment (BKPME). The tertiary treatments were applied on BKPME
      samples and in BKPME samples supplemented with extra concentration of each
      phenol. Tertiary treatments by Rhizopus oryzae and photo-Fenton oxidation were
      able of complete removal (100%) of phenols on BKPME samples whereas P. sajor caju
      and laccase were able of 60-85% removal. On BKPME samples with added
      concentration of each phenol, photo-Fenton was the only treatment capable of
      total phenols removal (100%), which suggests a great potential for its
      application.

PMID- 20683766
TI  - A pilot randomized controlled trial of omega-3 fatty acids for autism spectrum
      disorder.
AB  - We conducted a pilot randomized controlled trial to determine the feasibility and
      initial safety and efficacy of omega-3 fatty acids (1.3 g/day) for the treatment
      of hyperactivity in 27 children ages 3-8 with autism spectrum disorder (ASD).
      After 12 weeks, hyperactivity, as measured by the Aberrant Behavior Checklist,
      improved 2.7 (+/- 4.8) points in the omega-3 group compared to 0.3 (+/- 7.2)
      points in the placebo group (p = 0.40; effect size = 0.38). Correlations were
      found between decreases in five fatty acid levels and decreases in hyperactivity,
      and the treatment was well tolerated. Although this pilot study did not find a
      statistically significant benefit from omega-3 fatty acids, the small sample size
      does not rule out small to moderate beneficial effects.

PMID- 20683765
TI  - Distribution of laminin beta2, collagen type IV, fibronectin and MMP-9 in ovaries
      of the teleost fish.
AB  - Extracellular matrix in the ovarian follicle has been characterised for several
      mammalian species but there are no reports that describe the immunolocalisation
      of the extracellular matrix elements, matrix metalloproteinases, and its relation
      to plasma 17beta estradiol levels and follicular apoptosis during the teleost's
      reproductive cycle. The present study used immunohistochemistry to characterise
      the distribution of laminin beta2, collagen type IV, fibronectin and matrix
      metalloproteinases-9 (MMP-9). The TUNEL in situ technique was used to quantify
      apoptosis and indirect immunofluorimetric to determine plasma 17beta estradiol
      levels. The TUNEL-positive reaction associated with morphological features
      exhibited follicular apoptosis. During postovulatory follicle involution, the
      drop in plasma 17beta estradiol levels after spawning contributed to the intense
      apoptosis observed. By immunohistochemical analysis, laminin beta2 and collagen
      type IV were identified as the major constituents of the basement membrane. The
      loss of integrity of the basement membrane occurred due to lyses of the major
      constituents, and coincides with increased follicular apoptosis. The integrity of
      the basement membrane is important for the survival of follicular cells.
      Furthermore, the MMP-9 results suggest that this enzyme is involved in final
      oocyte maturation and regression of postovulatory follicles. Fibronectin was
      observed on the surface of follicular cells of the postovulatory follicle in P.
      argenteus, this being important for maintaining normal cell adhesion to
      extracellular matrix. In conclusion, our results suggest that the structure and
      composition of the extracellular matrix, and plasma 17beta estradiol levels
      related to apoptosis, play an important role during the follicular development
      and post-spawning involution in teleost fishes.

PMID- 20683767
TI  - Imitation assessment and its utility to the diagnosis of autism: evidence from
      consecutive clinical preschool referrals for suspected autism.
AB  - The present study sought to examine imitation difficulties as a risk factor for
      autism. Imitation aptitude was examined in 86 preschoolers suspected of autism
      (1.9-4.5 years) using the Preschool Imitation and Praxis Scale (PIPS).
      Differences between imitation, language, motor age-equivalents and nonverbal
      mental age were used to predict the diagnosis of autism. Multidisciplinary team
      diagnoses and ADOS-G classifications were used to differentiate children with
      autism spectrum disorders and non-spectrum developmental disorders. Two factors
      were found to be significantly associated with autism using simple logistic
      regression analyses: procedural imitation delay and receptive language delay. In
      a multivariable setting, only procedural imitation delay remained a significant
      predictor of autism. Results are new to the literature and require replications.

PMID- 20683768
TI  - Relation of melatonin to sleep architecture in children with autism.
AB  - Children with autism often suffer from sleep disturbances, and compared to age
      matched controls, have decreased melatonin levels, as indicated by urine levels
      of the primary melatonin metabolite, 6-sulfatoxymelatonin (6-SM). We therefore
      investigated the relationship between 6-SM levels and sleep architecture in
      children with autism spectrum disorders (ASD). Twenty-three children, aged 4-10
      years, completed two nights of polysomnography and one overnight urine collection
      for measurement of urinary 6-SM excretion rate. Parents completed the Children's
      Sleep Habits Questionnaire. We found that higher urinary 6-SM excretion rates
      were associated with increased N3 sleep, decreased N2 sleep, and decreased
      daytime sleepiness. The results warrant further examination to examine the
      effects of supplemental melatonin on sleep architecture and daytime sleepiness.

PMID- 20683769
TI  - Sympathetic neurons express and secrete MMP-2 and MT1-MMP to control nerve
      sprouting via pro-NGF conversion.
AB  - Recently, we have shown that high frequency electrical field stimulation (HFES)
      of sympathetic neurons (SN) induces nerve sprouting by up-regulation of nerve
      growth factor (NGF) which targets the tyrosine kinase A receptor (TrkA) in an
      autocrine/paracrine manner. There is increasing evidence that matrix
      metalloproteinase-2 (MMP-2) is not only involved in extracellular matrix (ECM)
      turnover but may also exert beneficial effects during neuronal growth. Therefore,
      this study aimed to investigate the regulation and function of MMP-2 and its
      major activator membrane type 1-matrix metalloproteinase (MT1-MMP) as well its
      inhibitor TIMP-1 in SN under conditions of HFES. Moreover, we analyzed molecular
      mechanisms of the beneficial effect of losartan, an angiotensin II type I
      receptor (AT-1)blocker on HFES-induced nerve sprouting. Cell cultures of SN from
      the superior cervical ganglia (SCG) of neonatal rats were electrically stimulated
      for 48 h with a frequency of 5 or 50 Hz. HFES increased MMP-2 and MT1-MMP mRNA
      and protein expression, whereas TIMP-1 expression remained unchanged. Under
      conditions of HFES, we observed a shift from pro- to active-MMP-2 indicating an
      increase in MMP-2 enzyme activity. Specific pharmacological MMP-2 inhibition
      contributed to an increase in pro-NGF amount in the cell culture supernatant and
      significantly reduced HFES-induced neurite outgrowth. Losartan abolished HFES
      induced nerve sprouting in a significant manner by preventing HFES-induced NGF,
      MMP-2, and MT1-MMP up-regulation. In summary, specific MMP-2 blockade prevents
      sympathetic nerve sprouting (SNS) by inhibition of pro-NGF conversion while
      losartan abolishes HFES-induced SNS by reducing total NGF, MMP-2 and MT1-MMP
      expression.

PMID- 20683770
TI  - One-pot synthesis of benzochromeno-pyrazole derivatives.
AB  - One-pot synthesis of different benzochromeno-pyrazole derivatives has been
      reported via reaction of aldehydes, 3-methyl-1H-pyrazol-5(4H)-one and alpha
      naphthol/beta-naphthol in the presence of sulfamic acid.

PMID- 20683771
TI  - Food insecurity and mental health: a pilot study of patients in a psychiatric
      emergency unit in Israel.
AB  - The objective of this study was to examine food insecurity among psychiatric
      patients and as a concern for mental health practitioners. Food security and
      psychological distress were measured among 113 patients hospitalized in a
      psychiatric emergency unit. Of 113 respondents 67 (59.3%) enjoyed food security
      and 46 (40.7%) lacked food security. Food insecure respondents showed a higher
      level of psychological distress than food secure respondents. A large proportion
      of in-patients may be suffering food insecurity which is negatively associated
      with their psychological well being. Mental health practitioners need to be aware
      of the potential association of food insecurity and mental distress among
      psychiatric patients.

PMID- 20683772
TI  - The relationship between case manager expectations and outcomes of persons
      diagnosed with schizophrenia.
AB  - The present study examined the relationship between case managers' expectations
      about the abilities of persons diagnosed with schizophrenia and the outcomes (as
      indicated via chart review) of a randomly selected sample of clients diagnosed
      with schizophrenia on their caseload. Results indicate that clients of case
      managers with higher expectations averaged significantly more months of progress
      in employment than clients of case managers with lower expectations. Case manager
      expectations were also better predictors of the number of days employed than
      other case manager and consumer characteristics, however the type of expectation
      was a critical determinant of the direction of the effect. Case manager
      expectations were not related to outcomes in living situation.

PMID- 20683773
TI  - Mathematical models of the homochiralisation of crystals by grinding.
AB  - We review the existing mathematical models which describe physicochemical
      mechanisms capable of producing a symmetry-breaking transition to a state in
      which one chirality dominates the other. A new model is proposed, with the aim of
      elucidating the fundamental processes at work in the crystal grinding systems of
      Viedma (Phys Rev Lett 94:065504, 2005) and Noorduin (J Am Chem Soc 130:1158-1159,
      2008). We simplify the model as far as possible to uncover the fundamental
      competitive process which causes the symmetry-breaking, and analyse other
      simplifications which might be expected to show symmetry-breaking.

PMID- 20683774
TI  - Polymorphism of serotonin receptor genes (5-HTR2A) and Dysbindin (DTNBP1) and
      individual components of short-term verbal memory processes in Schizophrenia.
AB  - Associations between polymorphisms in the T102C and A-1438G loci of the 5-HTR2A
      and the P1763 and P1578 markers of the DTNBP1 gene with the overall productivity
      and individual subprocesses of shortterm verbal memory were studied in 4-5
      patients with schizophrenia and 290 healthy subjects. Subjects were asked to
      reproduce immediately two lists of 10 words. The overall productivity of
      reproduction was assessed, along with the reproduction productivity of the first
      list (immediate memory or general attention), the effect of proactive
      interference, and the number of intrusions. Patients were significantly different
      from controls on all measures. Patients showed decreases in overall task
      performance productivity, in immediate memory productivity, and in the effect of
      proactive interference; fewer intrusions were seen. Both markers of the 5-HTR2A
      gene were associated with short-term memory productivity in the combined cohort:
      assessments were worse in T102C CC and A-1438G GG homozygotes. The P1763 marker
      of the DTNBP1 gene, conversely, had significant influences on the memory
      subprocesses reflected in the levels of interference and intrusions but had
      insignificant influence on overall productivity. Homozygotes for P1763G GG had
      the worst parameters. Overall, these data are consistent with the concept that
      these polymorphic genes are involved in different subprocesses of short-term
      memory both in normal subjects and in patients with schizophrenia.

PMID- 20683775
TI  - Efficacy of akatinol memantine in moderate cognitive impairments.
AB  - A six-month open clinical trial of the efficacy of Akatinol was conducted in 40
      patients with moderate cognitive impairments (MCI) using piracetam (20 patients)
      as reference agent; mean age was 67.7 +/- 7.2 years. Patient status was evaluated
      using a number of scales, questionnaires, and neuropsychological tests prior to
      treatment and at three and six months of treatment. Akatinol was given at a dose
      of 10 mg/day, and 20 patients received piracetam at a dose of 1200 mg/day.
      Studies were completed by 38 patients (95%) in the Akatinol arm and 18 (90%) in
      the piracetam arm. In the group treated with Akatinol, 5% reported deterioration,
      20% no change, 35% moderate improvement, 25% marked improvement, and 15% great
      improvement. In the Akatinol arm, the proportion of patients without effects was
      significantly lower, while the proportions of patients with marked and great
      improvements were significantly higher than in the piracetam arm. Overall
      evaluation of cognitive functions on the MMSE scale showed significant increases
      in both groups by the end of the third month, though only patients receiving
      Akatinol maintained the improvements to the end of the sixth month. Akatinol
      treatment also produced positive changes in the symptoms of depression,
      subjective symptoms, and quality of life. More marked positive changes were seen
      in the dysregulatory type of MCI than in the amnestic type of MCI. The concept of
      MCI with a high risk of transformation to dementia is introduced; in this
      situation, treatment with Akatinol may be particularly relevant.

PMID- 20683776
TI  - The potential of transcranial magnetotherapy in color and rhythm therapy in the
      rehabilitation of ischemic stroke.
AB  - A total of 116 patients with ischemic stroke were studied during the early
      recovery period. The patients were divided into four groups - three experimental
      groups and one control group. Of these, 87 patients in the first three groups
      received transcranial magneto- and/or color and rhythm therapy (TcMT, CRT) along
      with traditional treatment, while the 29 patients of the control group received
      basal treatment only. TcMT was performed using a bitemporal method, with a
      running field regime with a modulation frequency of 1-10 Hz. CRT consisted of an
      alternating scheme of stimulation of the left and right eyes with green and/or
      blue light with a period of 2-4 sec and an on time of 1 sec. Each of the three
      experimental groups (group 1 received TcMT, group 2 received CRT, and group 3
      received TcMT + CRT) received two courses of treatment separated by 1.5 months.
      After treatment, all experimental groups, particularly group 3, showed more
      marked improvements than the control group. Regression of neurological
      symptomatology on the Lindmark scale in group 3 was 9.5% greater than that in
      controls; improvements in impairments to activity and self-care ability on the
      Barthel scale were greater by 8.8%; memory and intellectual changes were also
      seen on the MMSE and the Luriya and Schulte tests. Rheography and
      electroencephalography demonstrated significant improvements in hemodynamics and
      alpha-rhythm differentiation and a 14.6% reduction in the proportion of patients
      with dysrhythmia in group 3 compared with the control group. The best result on
      all measures were obtained in patients given the combination of TcMT and CRT;
      TcMT had the greater influence on hemodynamics, while CRT had the greater effect
      on psychoemotional status. Both treatments were well tolerated and produced no
      side effects.

PMID- 20683777
TI  - Effects of memantine on convulsive reactions and the organization of sleep in
      krushinskii-molodkina rats with an inherited predisposition to audiogenic
      convulsions.
AB  - Krushinskii-Molodkina rats, which have a genetic predisposition to audiogenic
      convulsions, are used as a natural animal model for studies of the actions of
      anticonvulsants. It is important to understand the extent to which changes in
      glutamatergic synaptic transmission is involved in the mechanisms producing
      convulsive states and in the functional organization of the sleep-waking cycle in
      rats of this strain. The present report describes experiments addressing this, in
      which i.m. doses of 5 and 10 mg/kg of a noncompetitive NMDA glutamate receptor
      antagonist of the memantine type were given at different times (30 min, 1, 2, and
      3 h) before presentation of sound stimuli (sine-wave tones at 8 kHz, 90 dB).
      Effects on the latent periods of the initial motor excitation, the appearance of
      clonic convulsions of different intensities, and, finally, tonic convulsions with
      limb and tail extension were evaluated. The greatest attenuation of convulsive
      seizures, to a level consisting only of motor excitation, was obtained in 60% of
      the rats between 1 and 2 h after administration. There were no differences
      between the effects of doses of 5 and 10 mg/kg. When doses were given 3 h before
      sound provocation, convulsive reactions became more marked than at 2 h, though
      they were nevertheless more marked than in controls. Krushinskii-Molodkina rats
      with chronically implanted electrodes for recording brain electrical activity
      were used to study the effects of memantine on the organization of sleep. These
      experiments showed that the rats' sleep during the first hour after dosage
      consisted only of short episodes of superficial slow-wave sleep, and that even
      this sleep disappeared completely 54.4 +/- 4.9 and 39.9 +/- 5.2 min after
      administration of the agent at doses of 5 and 7 mg/kg, respectively. Rats showed
      a complete absence of sleep for 2 and 2.5 h, respectively, after which episodes
      of slow-wave sleep reappeared. The first episodes of REM sleep was seen in rats
      only after 3.3 +/- 0.2 and 3.7 +/- 0.2 h after memantine injections. The
      appearance of these episodes provided evidence that the effects of memantine on
      the activity of the somnogenic system of the animals' brains were complete and
      that recovery of the normal organization of the sleep-waking cycle had started.
      The synchronicity and codirectionality of the blocking action of memantine on
      sleep organization and measures of audiogenic convulsions in Krushinskii
      Molodkina rats is evidence for the involvement of glutamatergic synapses with
      NMDA receptors in both the regulation of the somnogenic systems and the
      pathogenesis of epileptiform manifestations in rats.

PMID- 20683778
TI  - Activation of the NO-ergic system of the nucleus accumbens on presentation of
      contextual danger signals.
AB  - Studies in Sprague-Dawley rats using intracerebral microdialysis combined with
      HPLC showed that presentation of the animals with a chamber in which they had
      previously acquired a conditioned reflex fear reaction (combination of a tone and
      electric shocks) led to increases in extracellular citrulline (a co-product of NO
      synthesis) in the medial segment of the nucleus accumbens. This increase was
      prevented by local administration of the NO synthase inhibitor 7-nitroindazole
      (0.5 mM). The increase was significantly smaller in amplitude than the increase
      in the citrulline level induced by combined presentation of the tone and the
      chamber but was no different from changes in citrulline levels seen during this
      test in the lateral segment of the nucleus accumbens. These data provide evidence
      that contextual danger signals activate neuronal NO synthase in the medial and
      perhaps the lateral segments of the nucleus accumbens, leading to increases in
      extracellular citrulline and, probably, increased NO production in this part of
      the brain.

PMID- 20683779
TI  - Identification of the minimal dose of Na2EDTA able to stimulate respiration in
      rats during hypothermia.

PMID- 20683780
TI  - Effects of visual environment complexity on saccade performance in humans with
      different functional asymmetry profiles.
AB  - Studies in 47 right-handed subjects with right and left leading eyes addressed
      the latent periods of visually-evoked saccades in the horizontal, vertical, and
      diagonal directions within the field of vision. Visual environments with three
      levels of temporospatial complexity and two standard time protocols of visual
      stimulation, with "gap" and "overlap," were used. In subjects with left leading
      eyes, saccades were more often performed with shorter latent periods in the
      direction ipsilateral to the leading eye than in the contralateral direction (53%
      versus 20%); among subjects with right leading eyes, the proportions with
      decreases in the latent periods in the ipsi- and contralateral directions were
      different (25% and 22%, respectively). Thus, there was a relationship between eye
      dominance and the spatial asymmetry of the latent periods of saccades.

PMID- 20683781
TI  - Morphofunctional changes in goldfish Mauthner neurons after application of beta
      amyloid.
AB  - The effects of applying aggregated beta-amyloid peptide fragment 25-35 on the
      three-dimensional structure and volume of Mauthner neurons (MN) and on motor
      asymmetry were assessed in goldfish using reconstructions based on serial
      histological sections. These experiments showed that the motor asymmetry of the
      fish was stable in the intact state and in controls and correlated tightly with
      structural asymmetry of neurons. beta-Amyloid produced large changes or inversion
      in motor asymmetry, which did not coincide with or even contradicted the
      structural asymmetry of MN. This occurred as a result of marked dystrophy or,
      conversely, hypertrophy of individual neurons and their individual dendrites,
      with changes in their proportions. It is suggested that the harmful action of
      beta-amyloid on MN structure and the discordant ("incorrect") behavior of the
      fish may result from mechanical deformation evoked by its tape-like fibrils.
      Overall, the results lead to the conclusion that MN provide a suitable system for
      studying the structural aspects of amyloidosis.

PMID- 20683782
TI  - Si se puede: using participatory research to promote environmental justice in a
      Latino community in San Diego, California.
AB  - Community-based participatory research (CBPR) increasingly is seen as a potent
      tool for studying and addressing urban environmental health problems by linking
      place-based work with efforts to help effect policy-level change. This paper
      explores a successful CBPR and organizing effort, the Toxic Free Neighborhoods
      Campaign, in Old Town National City (OTNC), CA, United States, and its
      contributions to both local policy outcomes and changes in the broader policy
      environment, laying the groundwork for a Specific Plan to address a host of
      interlocking community concerns. After briefly describing the broader research of
      which the OTNC case study was a part, we provide background on the Environmental
      Health Coalition (EHC) partnership and the setting in which it took place,
      including the problems posed for residents in this light industrial/residential
      neighborhood. EHC's strong in-house research, and its training and active
      engagement of promotoras de salud (lay health promoters) as co-researchers and
      policy change advocates, are described. We explore in particular the translation
      of research findings as part of a policy advocacy campaign, interweaving
      challenges faced and success factors and multi-level outcomes to which these
      efforts contributed. The EHC partnership's experience then is compared with that
      of other policy-focused CBPR efforts in urban environmental health, emphasizing
      common success factors and challenges faced, as these may assist other
      partnerships wishing to pursue CBPR in urban communities.

PMID- 20683783
TI  - Subcutaneous placement of access ports following laparoscopic adjustable gastric
      banding is a safe, cost-effective technique associated with low complication
      rates.

PMID- 20683784
TI  - Weight loss reporting: predicted body mass index after bariatric surgery.
AB  - BMI and %EBMIL are the most accurate methods for comparing results of patients
      after bariatric surgery. %EBMIL is based on BMI 25 as a constant end-point for
      all patients, but BMI 25 is easily achieved by patients with BMI < 50, whereas it
      is not so feasible for patients with BMI > 50. We were prompted to obtain by
      statistical methods a mathematical formula able to calculate the final BMI (FBMI)
      3 years after the operation, dependent on the initial or preoperative BMI (IBMI)
      of a multicenter group of morbid obese patients operated with different bariatric
      techniques. We also obtained a specific formula for each bariatric procedure of
      this group of patients. We propose the name Predicted BMI for the value obtained
      with these formulas and its application in the %EBMIL instead of the constant
      value of BMI 25. We have analyzed the IBMI and FBMI of a multicenter group of
      7,410 patients, subjected to different bariatric procedures with a minimum follow
      up of 36 months. Statistical methods with a linear regression model have been
      used to obtain the two types (global and specific) of Predicted BMI. We first
      obtained a general formula of PBMI = IBMI x 0.4 + 11.75 for the total population
      of patients, and a second specific formula for each bariatric technique: PBMI =
      IBMI x 0.43 + 13.25 + technique_correction_adjustment. Predicted BMI and its
      application to the %EBMIL may result in a more rational comparison of results of
      bariatric patients, bariatric techniques, and groups of bariatric surgeons.
      Predicted BMI may advance the BMI that each patient would probably achieve after
      surgery.

PMID- 20683785
TI  - Revisiting dietary cholesterol recommendations: does the evidence support a limit
      of 300 mg/d?
AB  - The perceived association between dietary cholesterol (DC) and risk for coronary
      heart disease (CHD) has resulted in recommendations of no more than 300 mg/d for
      healthy persons in the United States. These dietary recommendations proposed in
      the 1960s had little scientific evidence other than the known association between
      saturated fat and cholesterol and animal studies where cholesterol was fed in
      amounts far exceeding normal intakes. In contrast, European countries, Asian
      countries, and Canada do not have an upper limit for DC. Further, current
      epidemiologic data have clearly demonstrated that increasing concentrations of DC
      are not correlated with increased risk for CHD. Clinical studies have shown that
      even if DC may increase plasma low-density lipoprotein (LDL) cholesterol in
      certain individuals (hyper-responders), this is always accompanied by increases
      in high-density lipoprotein (HDL) cholesterol, so the LDL/HDL cholesterol ratio
      is maintained. More importantly, DC reduces circulating levels of small, dense
      LDL particles, a well-defined risk factor for CHD. This article presents recent
      evidence from human studies documenting the lack of effect of DC on CHD risk,
      suggesting that guidelines for DC should be revisited.

PMID- 20683786
TI  - A simple table lookup method for PET/CT partial volume correction using a point
      spread function in diagnosing lymph node metastasis.
AB  - OBJECTIVE: We evaluated the partial volume effect in PET/CT images and developed
      a simple correction method to address this problem. METHODS: Six spheres and the
      background in the phantom were filled with F-18 and we thus obtained 4 different
      sphere-to-background (SB) ratios. Thirty-nine cervical lymph nodes in 7 patients
      with papillary thyroid carcinoma (15 malignant and 24 benign) were also examined
      as a preliminary clinical study. First, we developed recovery coefficient (RC)
      curves normalized to the maximum counts of the 37-mm sphere. Next, we developed a
      correction table to determine the true SB ratio using three parameters, including
      the maximum counts of both the sphere and background and the lesion diameter, by
      modifying the approximation formula of the RC curves including the point-spread
      function correction. The full width at half maximum in this formula is estimated
      with the function of the SB ratio. RESULTS: In the phantom study, a size
      dependent underestimation of the radioactivity was observed. The degree of
      decline of RC was influenced by the SB ratio. In preliminary clinical
      examination, the difference in the SUV(max) between malignant and benign LNs thus
      became more prominent after the correction. The PV correction slightly improved
      the diagnostic accuracy from 95 to 100%. CONCLUSIONS: We developed a simple table
      lookup correction method for the partial volume effect of PET/CT. This new method
      is considered to be clinically useful for the diagnosis of cervical LN
      metastasis. Further examination with a greater number of subjects is required to
      corroborate its clinical usefulness.

PMID- 20683787
TI  - Histopathological effect of radiofrequency ablation therapy for primary breast
      cancer, with special reference to changes in cancer cells and stromal structure
      and a comparison with enzyme histochemistry.
AB  - Radiofrequency ablation (RFA) therapy is expected to be applicable to small
      breast cancers, but no criteria for its histopathological effect have yet been
      established. Using samples obtained from 15 patients who had undergone RFA and
      subsequent mastectomy, we compared the histopathological changes in the ablated
      area with the results of histochemical staining based on the reduction of
      nitroblue tetrazolium chloride (NBT) by nicotinamide adenine dinucleotide (NADH)
      diaphorase in frozen tissue sections, and looked for histological changes
      indicative of the effect of RFA on breast cancer. Grossly, the ablated area in
      most of the tumors was rough, gritty, less moist, and surrounded by a red
      congestive limbic zone. The ablated area showed no staining by the NADH
      diaphorase reaction, and cancer cells in the area showed marked destruction
      characterized by an unclear intercellular boundary, elongated eosinophilic
      cytoplasm, pyknotic "streaming" nuclei, and a poorly defined nuclear and
      cytoplasmic texture. At the same time, fibrous connective tissue also showed
      degenerative changes, becoming densely homogeneous with loss of its delicate wavy
      structure. The area in which RFA appeared to have been histopathologically
      effective was mostly concordant with the area in which the NADH diaphorase
      reaction was negative. In the periphery of the ablated area, however, cellular
      changes caused by RFA were less marked, although the NADH diaphorase reaction was
      visualized with NBT. A larger number of cases should be examined in order to
      establish criteria for the histopathological effect of RFA on breast cancer.

PMID- 20683788
TI  - Novel SPECT perfusion imaging agents with improved myocardial or liver kinetics:
      experimental studies and the need for clinical evaluation.

PMID- 20683789
TI  - Electronic structure modeling of dinuclear copper(II)-methacrylic acid complex by
      density functional theory.
AB  - A dinuclear centrosymmetric copper(II) complex with the formula [Cu(2)(mu
      maa)(4)(maaH)(2)] has been synthesized and experimentally characterized by IR,
      electronic spectroscopy, and X-ray single-crystal diffractometry. Starting from
      experimental X-ray geometry and using antiferromagnetic singlet ground state, gas
      phase geometry optimization was performed by density functional hybrid (B3LYP)
      method with 6-31G(d) and LANL2DZ basis sets. Gas-phase vibrational frequencies
      and single point energy (SPE) calculations have been carried out at the geometry
      optimized structure. Molecular electrostatic potential calculated at the
      optimized geometry and natural bond orbital analysis data have been extracted
      from SPE output. The gas-phase electronic transitions of the title complex were
      investigated by the time dependent-density functional theory (TD-DFT) approach
      with the same theory employing LANL2DZ basis set. Also the calculated UV-Vis
      based upon TD-DFT results and IR spectra were simulated for comparison with the
      experimental ones.

PMID- 20683790
TI  - Hydrogen-mediated Stone-Wales isomerization of dicyclopenta[de,mn]anthracene.
AB  - The mechanism of transformation of two radicals (R1p and R1i) obtained by
      addition of a hydrogen atom to an external and internal carbon atom of
      dicyclopenta[de,mn]anthracene (P1) was investigated. Two pathways were revealed.
      The first mechanism is a one-step process, whereas the second mechanism includes
      two transition states and a cyclobutyl intermediate. The formation of R1p and R1i
      and the homolytic cleavage of the radicals obtained during the isomerization
      processes were also examined. In both pathways the addition of a hydrogen atom to
      the internal carbon significantly lowers the activation energy for hydrogen
      mediated isomerization of P1 to acefluoranthene. This finding could be explained
      by the specific electronic structures of the transition states and intermediates
      participating in the isomerization processes.

PMID- 20683791
TI  - Are you ever too old to have a baby? The ethical challenges of older women using
      infertility services.
AB  - Older parenthood raises a variety of important factual and ethical questions.
      None of the questions have received sufficient attention despite the rapid
      expansion in the United States and other nations in the numbers of older parents.
      We do not know much about the safety, economic, and psychosocial impact of these
      emerging practices on children or parents. Nor have there been many analytical
      considerations of the ethical issues raised. We argue in this article that there
      are reasons for concern when older persons seek to utilize fertility treatments,
      including the safety of pregnancy for older women, risks posed to children
      delivered by older mothers, issues around what constitutes safe conditions for
      having a child relative to the age of parents, and the importance of guaranteeing
      that someone will serve in the parental role should an older parent or parents
      become disabled or die. To protect the best interest of children created by
      technology in new familial circumstances, internationally recognized and enforced
      standards for fertility clinics to follow ought to be enacted in making decisions
      about treating older parents seeking infertility services.

PMID- 20683792
TI  - Ethical obligation for restricting the number of embryos transferred to women:
      combating the multiple-birth epidemic from in vitro fertilization.
AB  - In vitro fertilization (IVF) is an increasingly effective and popular means of
      achieving pregnancy for infertile women, but contributes to a growing incidence
      of risky twin pregnancies. Despite studies demonstrating cost-effective means to
      achieve IVF pregnancy while strictly limiting the number of embryos transferred,
      multiple-embryo transfer remains the most common practice in the United States,
      and twin pregnancies continue to increase. IVF providers resist restricting these
      practices, arguing that this is counter to principles of procreative liberty,
      patient and professional autonomy, and free-market economics. We counter that
      physicians have a professional fiduciary responsibility to weigh issues of
      nonmaleficence to patients and just use of health care resources with patient
      desires. With oversight from professional organizations, providers should follow
      strict but medically appropriate restrictions on embryo transfer practices and
      work toward safer means of optimizing IVF outcomes than multiple-embryo transfer.

PMID- 20683793
TI  - Multifetal pregnancy reduction: evolution of the ethical arguments.
AB  - Multifetal pregnancy reduction (MFPR) was developed over 20 years ago to rescue
      higher-order multifetal pregnancies and has become a major component of improving
      the outcomes in infertility therapies. By definition, MFPR will always be
      controversial, but opinions do not follow the traditional "pro-life/pro-choice"
      dichotomy that has sabotaged the more generalized abortion debate. If one defines
      SUCCESS as a healthy mother and healthy offspring, clearly, with multiples, fewer
      are always safer. The ethical issues surrounding MFPR are for most people not a
      clear black-or-white but varying shades of gray. The ethical principle of
      proportionality takes precedence (i.e., trying to obtain the most good for the
      least harm while looking for areas of moral compromise to achieve the best
      outcomes).

PMID- 20683794
TI  - The ethical challenges of providing fertility care to patients with chronic
      illness or terminal disease.
AB  - The field of fertility is rapidly evolving, bringing opportunities for
      improvement in our patients' quality of life as well as bringing new ethical
      dilemmas. As medical science continues to advance, significant numbers of the
      reproductive-aged population are living with chronic and/or terminal conditions
      but have reasonable odds of lengthy survival and wish to have children. Likewise,
      there are adolescents diagnosed with cancer who are increasingly expected to
      achieve an improved, if not normal, life expectancy after treatment. Oftentimes
      these children are told they must sacrifice their ability to later have
      genetically related offspring; however, technologies to preserve fertility are
      changing this prognosis. Patients with chronic infection are living longer, more
      normal lives and are increasingly seeking reproductive assistance. Moreover,
      there is an increasing number of patients' families desiring posthumous use of
      gametes, which also raises ethical and legal issues. This article discusses
      ethical principles of bioethics and then highlights specific ethical issues
      through four plausible cases that may be seen in a fertility practice providing
      medical care to patients with chronic illness or terminal disease. It concludes
      that prompt referral of patients to the reproductive endocrinologist, along with
      a multidisciplinary approach to care, provides increased chances of successful
      treatment of this group of patients.

PMID- 20683795
TI  - The ethics of sex selection and family balancing.
AB  - Ethical concerns about the ethics of selecting the sex of a child predate current
      techniques of prenatal genetic diagnosis (PGD) and sperm sorting. The only
      methods previously available were highly problematic, as they involved
      infanticide or abortion of an unwanted sex. PGD is less problematic than the
      earlier methods, yet still troubling to some because it involves destruction of a
      healthy embryo and risks to women. The technique of sperm sorting, still in an
      experimental phase, is the least ethically problematic method, yet opponents
      argue that sex selection by any means involves sex discrimination and can have
      undesirable consequences. One such consequence is an imbalance in the sex ratio.
      This imbalance already exists in some Asian countries that favor male children,
      but is less likely in Western Europe and North America. There is increasing
      acceptance of family balancing as a reason for sex selection, but some people
      remain opposed to broadening the indications for sex selection of offspring
      beyond family balancing. Nevertheless, parents may have good reasons other than
      family balancing for choosing the sex of a future child. Such reasons may be
      justified by the principle of reproductive liberty.

PMID- 20683796
TI  - Ethics in egg donation: past, present, and future.
AB  - Since the advent of clinical human egg donation just over 25 years ago, ethical
      considerations have been central to its successful application and popular
      acceptance. Early in its history, "essentialist" arguments questioning the moral
      validity of the practice altogether were commonplace. More recently, most
      academic discussion has been focused on "consequentialist" issues relating to
      practical approaches to egg donation that minimize ethically troublesome
      consequences. Three issues that have attracted a bulk of the attention in this
      regard are compensation, postmenopausal pregnancy, and egg sharing. Although much
      consensus has been reached on some very controversial issues, the enormous
      potential of increasingly successful oocyte cryopreservation, as well as emerging
      stem cell technologies, is very likely to provide abundant fuel for the continued
      debate of provocative and contentious ethical issues in human egg donation.

PMID- 20683797
TI  - Posthumous assisted reproduction.
AB  - Cryopreservation of gametes and embryos allows for children to be conceived after
      the death of their genetic parents through the process of posthumous assisted
      reproduction (PAR). Although the techniques are routine, the moral and ethical
      details are controversial and remain unsettled. Furthermore, there are numerous
      medicolegal implications that complicate matters. The principal parties to be
      considered are the decedent, the child who will be born of PAR, the significant
      other requesting the procedure, other living children, and even society at large.
      Numerous case studies exist and expert opinions have been published recognizing
      PAR as a vexing ethical issue. Most experts agree that explicit written consent
      forms signed at the time of cryopreservation are the best method to minimize some
      of the controversy involved with PAR.

PMID- 20683798
TI  - The use of eggs and embryos in stem cell research.
AB  - Stem cell research has enormous potential to advance knowledge about many
      diseases but poses critical ethical issues. Many countries and U.S. states have
      developed policies concerning this area that over time will surely evolve, yet
      certain underlying ethical principles and tensions will no doubt continue to
      remain key. Overall, the basic ethical principles of autonomy, beneficence,
      nonmalfeasance, and justice are crucial but have been viewed, interpreted, and
      applied differently by policy makers and others. Controversies remain concerning
      what degree of respect eggs and embryos should receive; whether egg donors should
      be compensated, and if so, how much; what exactly to include in informed consent;
      and how to ensure appropriate oversight by institutional review boards and
      embryonic stem cell research oversight committees. This article addresses these
      areas and ways of approaching them, to adhere to important ethical principles,
      while helping to advance research that has the potential to help innumerable
      patients.

PMID- 20683801
TI  - Tribute to Professor Mark Ylvisaker and traumatic brain injury. Introduction.

PMID- 20683802
TI  - Management of traumatic brain injury: the influence of Mark Ylvisaker.

PMID- 20683803
TI  - Training everyday communication partners for individuals with traumatic brain
      injury: the influence of Mark Ylvisaker.
AB  - This lead article outlines some of the seminal concepts introduced by Mark
      Ylvisaker in collaboration with his colleague Tim Feeney and describes the
      influence of this work on the development of an everyday communication partner
      training program for families and social networks of people with traumatic brain
      injury.

PMID- 20683804
TI  - There's always something that works: principles and practices of positive support
      for individuals with traumatic brain injury and problem behaviors.
AB  - Behavioral and cognitive problems are among the most common and troubling
      consequences of traumatic brain injury Furthermore, behavioral and cognitive
      challenges typically develop in complex ways, necessitating an integrated
      approach to intervention and supports. This article summarizes literature on
      interventions positively affecting the behavioral outcomes for individuals with
      brain injury. This literature extends many of the traditional approaches to
      behavioral intervention and cognitive rehabilitation to include positive
      behavioral support and the development of personally meaningful activities for
      program development. In addition, the article provides a framework for
      intervention based on the decades-long work of Mark Ylvisaker, which is founded
      on positive principles of assessment and treatment and is implemented in a
      context-sensitive manner that integrates cognitive and behavioral intervention
      themes and focuses on the development of self-regulation.

PMID- 20683805
TI  - The positive behavioral momentum of Mark Ylvisaker.
AB  - Mark Ylvisaker inspired many people to believe they had the skills to help
      children and adults with brain injury live a meaningful life. He was thoroughly
      multidisciplinary in his approach, but also felt strongly that communication was
      the cornerstone of effective behavior management and that speech-language
      pathologists could make a unique contribution in the everyday lives of
      individuals with cognitive-communication disorders. This article recognizes his
      profound influence on the author's research, teaching, and clinical practice and
      was written in the spirit of paying forward the knowledge he shared.

PMID- 20683806
TI  - Dogs and other metaphors: reflections on the influence of Mark Ylvisaker.
AB  - Mark Ylvisaker's death in 2009 marked the sad cessation of a prolific and rich
      discourse regarding what matters in brain injury rehabilitation. In this article,
      I reflect on how my own work has converged with and been influenced by this great
      thinker and doer. My own work, like Ylvisaker's, has been oriented toward finding
      contextually relevant ways of assessing and remediating communication and social
      impairments in people with severe traumatic brain injury. In this article, common
      themes between Ylvisaker's work and my own are explored, including the usefulness
      of pragmatic language theory, which helps clarify why context is important when
      determining whether language is appropriate or not, and also to help reveal where
      problems occur in the use of subtle, diplomatic, or inferred meanings. This
      article also reflects upon Ylvisaker's models for remediation and the extent to
      which these can be encompassed within (as well as shape) more traditional models
      of social skills training.

PMID- 20683807
TI  - Mark Ylvisaker's influence on scripts, videos, and projects within a South
      African context.
AB  - The current article overviews a range of collaborative group projects undertaken
      by members of the Conversation Groups for individuals living with aphasia and
      cognitive-communication disorders in the Department of Communication Pathology,
      University of Pretoria, South Africa. Projects work toward creating networks of
      support and lessening barriers for the individual living with aphasia and
      cognitive-communication disorders. The article highlights the pervasive and far
      reaching influence across continents of Professor Mark Ylvisaker's philosophy,
      writings, and personal teachings on both Conversation Group projects as well as
      student clinician-training practice in the University of Pretoria context. In
      addition, Ylvisaker's influence is described on the development of a
      collaborative communication partner-training program within a South African
      retail supermarket environment, highlighting the effort to remove barriers
      between employees and customers with a cognitive-communication disability
      specifically.

PMID- 20683808
TI  - Clinical influences.
AB  - Mark Ylvisaker influenced a paradigm shift on approaches to assessment and
      intervention of individuals with a traumatic brain injury (TBI). This article
      describes the influence of Mark Ylvisaker on my speech-language therapy practice
      in TBI rehabilitation, from shaping assessment research through supporting a
      practical, problem-solving approach to intervention. In this article, only a
      small selection of his therapeutic concepts and recommendations are described.
      The concepts selected-context and meaningfulness, collaboration, and measuring
      performance-are those that are pertinent to functional communication assessment.
      The three interventions chosen illustrate the applicability of Mark Ylvisaker's
      work in different contexts and across different levels of disability following
      TBI. They are also selected as they promote personally satisfying communication
      for the client and illustrate the contribution that speech-language therapy may
      make to TBI rehabilitation overall.

PMID- 20683809
TI  - Placing brain injury rehabilitation in the context of the self and meaningful
      engagement.
AB  - Since his publications began to appear in the mid 1980s, Mark Ylvisaker has
      shaped the way clinicians worldwide approach brain injury rehabilitation. His
      body of work reflects his exceptional ability to draw together theories, ideas,
      and practices from multiple disciplines and paradigms culminating in the
      development of a clinically powerful framework to facilitate change in behavior.
      The focus of this article is two core aspects of Mark Ylvisaker's work that have
      had a significant impact on my own work. These aspects involve (1) using
      conceptualization of self or identity construction as a guide for developing
      rehabilitation goals and (2) centralizing meaningful activity within the
      intervention process. In a small way, this article is a tribute to an exceptional
      man who was dedicated to improving the lives of people with brain injury and in
      doing so succeeded in improving the lives of all who had the privilege of knowing
      him and knowing his work.

PMID- 20683810
TI  - [Impact factor 2009].
AB  - The second impact factor for the journal was published by the Institute of
      Scientific Information (ISI) with 0.646 in June of this year. A further
      consolidation of the journal as a major scientific "brick" for science and
      research as the relevant "base block" of the "building" of the specialty has been
      hereby achieved.

PMID- 20683811
TI  - [Treatment of painful neuromas via end-to-side neurorraphy].
AB  - INTRODUCTION: Management of the painful neuroma has been subject to controversy
      since the earliest descriptions of this disabling problem. Today, treatment is
      limited to resection of the neuroma and implantation of the nerve in a muscle at
      a location where it is safe from irritation and trauma. This however is not
      attainable in many cases and it is our clinical experience, that nerves without a
      target remain a source of constant discomfort and pain. Recently we reported of
      the feasibility of neuroma prevention through end-to-side neurorraphy into
      adjacent sensory and/or motor nerves to provide a target for axons deprived of
      their endorgan. Here we report of our first clinical experience with this method
      in sixteen patients with longstanding upper and lower extremity neuromas.
      PATIENTS AND METHODS: 16 patients were included in this study. All had neuromas
      of different sensory nerves of both the upper and lower extremity. 11 were of
      iatrogenic origin, 5 were caused by different traumas. 8 had previous attempts to
      surgically treat the neuroma. Finally, all were treated by end-to-side
      neurorraphy into adjacent nerves. Postoperatively quantitative sensorymotor
      testing was performed to evaluate possible changes of nerve function of the
      recipient nerves. Pain was evaluated by visual analogue score and changes in pain
      medication. RESULTS: In no patient a sensory or motor deficit or painful
      sensations were induced in the target area of the recipient nerve. Some had
      dysaesthesias for about 6 months, which finally subsided. All but 1 patient
      improved in their symptoms at a follow-up of more than 2 years. CONCLUSION:
      Previous experimental work and present clinical results suggest that axons of a
      severed peripheral nerve that are provided with a pathway and target through an
      end-to-side coaptation will either be pruned or establish some type of end-organ
      contact so that a neuroma can be prevented without inducing sensory or motor
      dysfunctions in the recipient nerve.

PMID- 20683812
TI  - Head hair reduces sweat rate during exercise under the sun.
AB  - The purpose of this study was to evaluate the effects of human head hair on
      thermoregulation during exercise carried out under solar radiation. 10 healthy
      male subjects (mean+/-SD: 25.1+/-2.5 yr; height: 176.2+/-4.0 cm; weight: 73.7+/
      6.7 kg; VO(2max) 56.2+/-5.3 mLO(2).kg (-1).min (-1)) took part in 2 1 h-long
      trials of continuous exercise on a treadmill at 50% VO2(max) under solar
      radiation that were separated by at least 2 days. Whereas for the first trial
      they retained their natural head hair (HAIR), in the second trial their hair was
      totally shaved (NOHAIR). Several properties were measured, including
      environmental heat stress (Wet Bulb Globe Temperature index - WBGT,  degrees C),
      heart rate, rectal temperature, skin temperature, head temperature, and global
      sweat rate. The main findings were that whereas there was a lower sweat rate in
      the HAIR condition (HAIR: 7.08+/-0.79 vs. NOHAIR: 7.67+/-0.79 g.m (-2).min (-1);
      p=0.03), there were no significant differences in any of the other variables
      between the HAIR and NOHAIR trials. In conclusion, the presence of head hair
      resulted in a lower sweat rate.

PMID- 20683813
TI  - Anterograde and retrograde flow anastomoses to the internal mammary vessels in
      the third intercostal space.

PMID- 20683814
TI  - Supporting facial transplantation with the pillars of bioethics.
AB  - Facial transplantation has recently been offered to patients with severely
      disfigured faces not amenable to functional reconstruction with autologous
      tissues. Arguments against this procedure include risks of immunosuppression, the
      concern that it will be done for cosmesis, the belief that acceptable
      reconstruction can be achieved with autologous tissues, the potential impact on
      the patient of graft failure, and the concern that the procedure may be adopted
      by unqualified centers. If we look to bioethics to help us dissect the question
      of whether or not facial transplantation should be performed, we see that the
      majority of the arguments have been proscriptive rather than prescriptive. There
      are valid arguments in favor of facial transplantation based on the prescriptive
      pillars of bioethics: autonomy, justice, and beneficence. This article attempts
      to reframe the dialogue in a prescriptive manner.

PMID- 20683815
TI  - Correlation of clinical and MRI staging in cervical carcinoma treated with
      radiation therapy: a single-center experience.
AB  - PURPOSE: To correlate clinical and MRI findings in patients with cervical
      carcinoma treated with radiation therapy (RT). MATERIALS AND METHODS: Forty-two
      patients with pretreatment IB-IVA cervical carcinoma were included in this
      retrospective study. Pre- and post-treatment MRI findings of the patients were
      reevaluated and compared with clinical staging. Six-month, one-year, and two-year
      follow-up imaging by MR was performed for 36, 20, and 7 patients, respectively.
      The correlation between clinical and MRI findings was assessed by a Spearman's
      rho (rank correlation) test. Univariate analyses were performed to identify the
      prognostic significance of the tumor volume and lymph node status. RESULTS: Pre
      treatment correlations between MRI and clinical findings for diagnoses without
      parametrial invasion, with parametrial invasion, and with pelvic sidewall
      invasion were 71.0%, 64.7%, and 15.8%, respectively. According to the Spearman's
      rho (rank correlation) test, the parametrial invasion correlation was poor (r =
      0.410, P < 0.01). The correlation of clinical and MRI findings at 6 months was
      88.9% (r = 0.674, P < 0.0001). CONCLUSION: In advanced cervical cancer, the
      correlation of clinical and MRI staging prior to neoadjuvant RT was low despite a
      high correspondence in the assessment of local response after RT.

PMID- 20683816
TI  - Acute abdomen caused by a small bowel perforation due to a clinically unsuspected
      fish bone.
AB  - We report the case of a 78-year-old woman with a three-day history of abdominal
      pain and vomiting. An abdominal plain film showed a distended small bowel loop
      and no signs of free intra-abdominal gas. An abdominal ultrasound revealed a mass
      containing a linear, hyperechoic structure. The mass was connected through a
      sinus tract to an adjacent aperistaltic small bowel loop. A laparotomy revealed a
      jejunal perforation and an omental granuloma containing a fish bone. Accidentally
      ingested foreign bodies should always be suspected in cases of acute abdomen, and
      ultrasonography remains a firstline examination tool for preoperative diagnoses
      of unsuspected foreign bodies and their complications.

PMID- 20683817
TI  - Chemoembolic lobectomy: imaging findings of hepatic lobar volume reduction after
      transcatheter arterial chemoembolization.
AB  - Hepatic lobar atrophy-hypertrophy complex formation is an uncommonly reported
      sequella of hepatic arterial embolotherapy procedures. Whereas radiation-induced
      hepatic lobar ablation has been described after intra-arterial therapy with
      yttrium-90 microspheres, this phenomenon has not been reported after
      transcatheter arterial chemoembolization. Here, we report a case of prominent
      hepatic lobar atrophy with contralateral lobar hypertrophy after
      chemoembolization and suggest a mechanism by which arterial embolization
      contributes to the volumetric response.

PMID- 20683818
TI  - MR cisternography: is it useful in the diagnosis of normal-pressure hydrocephalus
      and the selection of "good shunt responders"?
AB  - PURPOSE: The aim of this study was to evaluate the efficiency of MR
      cisternography (MRC) in the diagnosis of idiopathic normal-pressure hydrocephalus
      (INPH) and in the prediction of the response to shunt treatment. MATERIALS AND
      METHODS: Thirty-six patients with the diagnosis of "probable INPH" were included
      in the study group and 15 asymptomatic age-matched individuals were included in
      the control group. Pre-contrast T1-weighted (T1W) imaging was followed by
      intrathecal administration of 1 ml gadopentetate dimeglumine. Post-contrast T1W
      images were taken at the 12th, 24th and 48th hours. The presence of contrast
      material in the lateral ventricles for more than 24 hours was accepted as a
      positive diagnosis of INPH. Data from both groups were compared statistically.
      Statistical significance was accepted for P < 0.05. RESULTS: All of the INPH
      patients had remaining contrast material in their lateral ventricles at the 12th
      and 24th hours, while only 28 (78%) patients had contrast material remaining at
      the 48th hour after MRC. Only 3 (20%) of the control cases had remaining contrast
      material in their lateral ventricles at the 24th hour. No contrast material was
      present in the control cases at the 48th hour. The contrast material was found to
      be significantly more prevalent in the INPH patients at the 24th and the 48th
      hours compared with the control cases (P < 0.001). Shunt placement was performed
      in 14 INPH patients, and eight improved after shunt placement. All patients
      (100%) who improved after shunt placement had remaining contrast material in
      their lateral ventricles at the 24th and at the 48th hours. The sensitivity and
      specificity of MRC in the prediction of the response to shunt treatment were 100%
      and 17%, respectively. CONCLUSION: MRC does not use ionizing radiation and is
      generally a useful procedure to diagnose NPH and to predict a positive response
      to shunt treatment; thus, we recommend MRC after routine MRI in patients with the
      presumed diagnosis of NPH.

PMID- 20683819
TI  - Iatrogenic perforation of the left heart during placement of a chest drain.
AB  - Chest drain placement is a standard procedure for treating pneumothorax and
      pleural effusions and has a low complication rate. It is a safe and efficient
      procedure if image guidance is used. If the anatomic orientation is hampered and
      neither air nor fluids can be initially aspirated, more complex imaging than a
      chest x-ray is indicated to avoid major complications. We report the case of an
      88-year-old male patient suffering from chronic heart failure who was admitted to
      another hospital following acute cardiac decompensation. Because of dyspnea with
      voluminous bilateral effusions, an attempt was made to drain the left pleural
      cavity. A malposition of the chest drain was suspected because blood was
      initially draining from the catheter. The hemodynamically stable patient was
      referred to our university hospital, where computed tomography of the chest
      revealed the location of the intercostal drain. The drain had perforated the left
      ventricle, run through the mitral valve and exited the left atrium via a
      pulmonary vein, ending in the middle lobe. The patient was brought to the
      surgical theater, where cardiac surgeons performed a left anterolateral
      thoracotomy and extracted the drain successfully. Three days later, the patient
      was discharged from our hospital in a good general condition.

PMID- 20683820
TI  - MRI for acute neurologic complications in end-stage renal disease patients on
      hemodialysis.
AB  - Acute cerebrovascular disease is one of the most frequent causes of mortality and
      morbidity in patients on long-term hemodialysis therapy. Early recognition of
      cerebrovascular events improves the prognosis and quality of life of end-stage
      renal failure patients. This paper reviews the magnetic resonance imaging
      features of acute neurological findings in patients with end-stage renal failure.

PMID- 20683821
TI  - Examining correlates of methamphetamine and other drug use in pregnant American
      Indian adolescents.
AB  - American Indian and Alaska Native (AI/AN) adolescents have high rates of
      pregnancy, as well as alcohol, marijuana, cocaine, and, increasingly,
      methamphetamine (meth) use. The progression of adolescent drug use to meth use
      could have devastating impacts on AI communities, particularly when youth are
      simultaneously at risk for teen childbearing. In order to inform future
      prevention efforts, this study explores correlates of meth use in a sample of
      pregnant AI teens, with a focus on sociodemographic, familial, and cultural
      factors and use of other drugs.

PMID- 20683822
TI  - Assessing health-related quality of life in Northern Plains American Indians:
      prominence of physical activity as a health behavior.
AB  - Associations of behavioral health risks and healthy behaviors with self-reported
      health-related quality of life measures were investigated in a Northern Plains
      American Indian sample. Participants were surveyed in person using the Behavioral
      Risk Factor Surveillance Survey. The results showed that regular physical
      activity was significantly associated with better self-reported overall health,
      fewer mentally unhealthy and activity limitation days in the past 30 days, and
      with a greater number of good health days.

PMID- 20683823
TI  - Urban Indian voices: a community-based participatory research health and needs
      assessment.
AB  - This community-based participatory research (CBPR) project utilized a mixed
      methods survey design to identify urban (Tulsa, OK) American Indian (AI)
      strengths and needs. Six hundred fifty AIs (550 adults and 100 youth) were
      surveyed regarding their attitudes and beliefs about their community. These
      results were used in conjunction with other community research efforts to inform
      program development, support proposals for external funding, and develop a
      comprehensive service system model to be implemented in the community.

PMID- 20683824
TI  - [Perception of zoonosis in veterinary medicine and society].
AB  - A transdisciplinary project was undertaken by veterinarians and historians to
      investigate various aspects of potential zoonotic diseases that were classified,
      or have been seriously considered as reportable diseases in Switzerland (bovine
      spongiform encephalopathy [BSE], brucellosis, neosporosis, tuberculosis). Above
      all we were interested in the scientific and societal background which is
      necessary to declare an infectious disease being a reportable disease which needs
      to be eradicated. Results of this study have shown that the time interval between
      the first recognition of an infectious disease and the implementation of national
      control measures can vary greatly. In the post modern information based society,
      the interval between recognition of a new emerging disease and its eradication
      program becomes much shorter when the disease in question has a zoonotic
      potential. The historic correlation is not used as a history of progress. It is
      presented to explain the different recognition of risk and the broad context of
      measurements in society to fight against zoonosis.

PMID- 20683825
TI  - Disease awareness of the poultry keepers in Switzerland and their access to
      information concerning highly pathogenic avian influenza.
AB  - The passive surveillance of highly pathogenic avian influenza (HPAI) in domestic
      poultry is based essentially on the reporting of suspicious clinical cases by the
      poultry keepers to the veterinary services. As little was known about HPAI
      disease awareness among Swiss poultry keepers, a cross-sectional study was
      conducted among poultry keepers in Switzerland in 2007. For data triangulation
      and complementary information, interviews have been conducted with experts of
      poultry marketing organizations. The main information source used by the poultry
      keepers was mass media. Having a non-commercial poultry husbandry was
      significantly associated with lower knowledge scores. Non-commercial poultry
      keepers felt neglected by the veterinary authorities. Risks perceived by the
      poultry keepers reflected well the officially communicated risks for HPAI
      introduction. By highlighting the needs and the knowledge level of the poultry
      keepers, we make recommendations with regard to more efficient information
      exchange between poultry keepers and veterinary authorities. The main challenge
      will be to consistently integrate non-commercial poultry keepers in the formal
      information channels.

PMID- 20683826
TI  - [The use of a GnRH vaccine in mares and stallions to influence undesirable
      behavior: a retrospective study of 31 cases].
AB  - The aim of this study was to investigate the effect of a GnRH vaccine (Equity) on
      behavior and gonadal function in horses with unwanted behavior. The reason for
      the treatment was asked using a questionnaire and the findings of physical
      examination, rectal palpation as well as rectal ultrasonography, were recorded.
      The results of these examinations and the behavior of 21 mares and 10 stallions
      before the first and after the second administration of the GnRH vaccine were
      compared. In 84 % of all cases a decrease of the unwanted behavior could be
      observed. In the mares the ovaries were significantly (p <or= 0.05) smaller after
      vaccination than before. The largest and the second largest follicle on the
      ovaries were also significantly smaller after vaccination. In the stallion there
      was no significant difference in the size of testicles before and after
      vaccination. The study showed that the vaccine is well tolerated in horses and
      only little local adverse reactions appeared in 6.5 % of all cases.

PMID- 20683827
TI  - [Ultrasonographic findings in a cow with extraskeletal chondroblastic
      osteosarcoma of the neck region].
AB  - This case report describes the clinical, ultrasonographic and pathological
      findings in a five-year-old Swiss Braunvieh cow with extraskeletal chondroblastic
      osteosarcoma of the neck region. The cow was referred because of a firm, non
      painful swelling, approximately 25 cm in diameter, which was situated mainly on
      the lower left side of the neck but extended to the right. Ultrasonographic
      examination of the mass revealed a chambered structure containing echoic material
      that was separated by hyperechoic septa. Chondroblastic osteosarcoma was
      diagnosed based on histological evaluation of a biopsy sample, and the diagnosis
      was confirmed by postmortem examination.

PMID- 20683831
TI  - Vascular access using the superficial femoral vein.
AB  - PURPOSE: The superficial femoral vein (SFV) provides an alternative autologous
      conduit for fistula formation in patients who might otherwise require a
      prosthetic graft for hemodialysis (HD) access. The purpose of this study was to
      assess the results of this technique. METHODS: Patients who underwent formation
      of a SFV fistula were identified from a prospectively maintained database.
      Casenotes were reviewed for details of the operation, complications, subsequent
      interventions, and to determine whether the fistula was used for vascular access.
      RESULTS: Fifteen patients (seven males, eight females; median age 53, range 28-72
      yrs) were identified. Patients had a median of four (range 2-9) previous
      fistulae. In three patients, the mobilized SFV was transferred to the upper limb
      while 12 patients had lower limb fistulae. Twelve patients (80%) used their SFV
      fistula for HD. Eleven patients developed a wound complication (infection,
      dehiscence, hematoma or bleeding), with four patients returning to theater for
      formal exploration and three requiring application of a vacuum dressing. Two
      patients developed post-operative lower limb ischemia. Two patients died during a
      median follow-up time of 7 (range 1-27) months. CONCLUSION: In selected patients
      who have exhausted conventional routes for vascular access the SFV fistula can be
      used for the maintenance of HD. There is, however, significant associated
      morbidity and repeated intervention is often required.

PMID- 20683832
TI  - Access flow reduction and recurrent symptomatic cephalic arch stenosis in
      brachiocephalic hemodialysis arteriovenous fistulas.
AB  - BACKGROUND: Recurrent cephalic arch stenosis (CAS) has been linked to high flow
      and has a high rate of recurrence following angioplasty. This study investigates
      the effectiveness of access flow reduction in decreasing rapidly recurrent
      symptomatic CAS. METHODS: A retrospective study of patient records from February
      2005 to April 2009 was conducted. Patients with brachiocephalic fistulas who had
      undergone two or more instances of cephalic arch angioplasty within 3 months, and
      thereafter underwent flow reduction via banding of the access inflow (n=33) were
      included. A before-and-after analysis was conducted: the rates of cephalic arch
      angioplasty were calculated for each patient before and after the banding
      procedure, and compared via a paired t-test. RESULTS: At 3, 6, and 12 months, the
      cephalic arch primary lesion patency was 91%, 76%, and 57%. The cephalic arch
      intervention rate was reduced from 3.34 to 0.9 per access-year (t=7.74, p<.001).
      The average follow-up time was 14.5 months (range, 4.8-32). CONCLUSION: Flow
      reduction of a brachiocephalic arteriovenous hemodialysis fistula may effectively
      diminish the incidence of symptomatic CAS.

PMID- 20683833
TI  - Oxidized ATP inhibits T-cell-mediated autoimmunity.
AB  - T cells directed against self antigens play an important role in several
      autoimmune diseases. The available immunosuppressive compounds used to treat
      autoimmune diseases are limited, and often they have side effects that limit
      their application. T cells express ATP receptors, which could be new target
      molecules to treat autoimmune disease. Here we analyzed the effect of oxidized
      ATP (oxATP), an inhibitor of the ATP receptor P2rx7, in different murine models
      of T-cell-mediated autoimmune diseases. Treatment with oxATP inhibited
      proliferation and effector function of T cells. In the systems we used, oxATP did
      not obviously interfere with the innate immune response, but strongly reduced
      antigen-specific T-cell responses. This treatment ameliorated T-cell-mediated
      autoimmune type I diabetes and autoimmune encephalitis in mice. In conclusion,
      oxATP was found to strongly inhibit activated T cells and could thus be used to
      target T-cell-mediated autoimmune disease.

PMID- 20683834
TI  - The impact of carboxyalkylation of branched polyethylenimine on effectiveness in
      small interfering RNA delivery.
AB  - BACKGROUND: Carboxyalkylation of branched 25 kDa polyethylenimine (PEI) was
      considered to reduce the positive surface charge of the polymer without reducing
      its 'proton sponge' buffering capacity, and to provide alkylene domains for
      hydrophobic interactions, thus generating optimized novel PEI carriers for
      efficient delivery of small interfering RNA (siRNA). METHODS: Substitution of PEI
      was evaluated in the range of 6 to > 50 mole percentage of primary amines.
      Additionally, variation of the carboxyalkyl chain (one to 15 methylene groups)
      was explored to modulate the carrier hydrophobicity. Carriers were characterized
      in their buffering capacity, capability of siRNA polyplex formation, and
      cytotoxicity. Marker gene-silencing efficacy was evaluated using Neuro2A-eGFPLuc
      neuroblastoma cells. RESULTS: Carboxyalkylation strongly reduced cytotoxicity of
      PEI and improved siRNA mediated luciferase gene knockdown. An optimum silencing
      activity was observed at an alkylcarboxylation degree of 6-9 mole percentage of
      primary amines and with a broad range of carboxyalkylene chains (containing one
      to 15 methylene groups). Strongly enhanced gene-silencing efficacy also was
      observed when the biocompatible polymers were separately added at 1 h after
      transfection with tolerated doses of standard PEI25/siRNA polyplexes.
      CONCLUSIONS: Carboxyalkylation of branched 25 kDa PEI resulted in polymers with
      strongly reduced cytotoxicity and improved silencing efficacy. Mechanistic
      studies demonstrated that the presence of a surplus of free carboxyalkylated
      polymer is responsible for the improved siRNA delivery.

PMID- 20683835
TI  - Asymmetric total synthesis of solandelactone E: stereocontrolled synthesis of the
      2-ene-1,4-diol core through a lithiation-borylation-allylation sequence.

PMID- 20683837
TI  - Assessing the impact of carryover effects on the variances of estimators of
      treatment differences in crossover designs.
AB  - Different models that include carryover effects have been studied in the optimal
      design literature. It has been suggested that the use of these models results in
      increased variances of estimated contrasts of the direct treatment effects,
      leading to inferior estimators in terms of precision. Under a number of models
      and selected designs, we present variance expressions for the pairwise
      differences of direct treatment effects and observe that adjusting for carryover
      effects need not affect the precision of estimators negatively. We investigate
      the existence of designs that produce estimators with relatively small variances
      under all models considered. We conclude that even if a model is not correct, it
      can still be useful in increasing the precision of estimators for treatment
      contrasts.

PMID- 20683838
TI  - Reply: Case series of painful legs and moving toes: clinical and
      electrophysiological observations.

PMID- 20683839
TI  - Multiple system atrophy is associated with changes in peripheral insulin-like
      growth factor system.
AB  - Insulin-like growth factors (IGF-I and IGF-II) have been shown to have several
      neurotrophic actions and IGF system may be impaired in neurodegenerative
      disorders. The aim of this study was to investigate the IGF system in patients
      with MSA and to evaluate correlations between this endocrine system and clinical
      features of the disease. Serum levels of IGF-I, IGF-II, insulin, IGF-binding
      protein 1 (BP1), and IGF-binding protein 3 (BP3) were measured in 25 patients
      with probable MSA and 25 age, sex and BMI-matched healthy controls. Clinical
      status of each patient was evaluated with the Unified Multiple System Atrophy
      Rating Scale (UMSARS) Part II and the Hoehn and Yahr rating scale. IGF-I levels
      were significantly higher in MSA (164.1 + 66.2 MUg/L) than in healthy controls
      (111.7 + 60.3 MUg/L; p = 0.001). Insulin levels were significantly higher in MSA
      patients (21.9 +/- 14.4 MUU/mL) than in healthy controls (13.3 +/- 5.1 MUU/mL, p
      = 0.048). No significant difference was found in serum IGF-II, IGF-BP1, and IGF-
      BP3 levels between patients with MSA and healthy controls. There was a trend
      toward significantly higher IGF-II levels in MSA patients with UMSARS score <26
      (1026.3 +/- 442.6 MUg/L) than MSA patients with UMSARS score >26 (796.1 +/- 234
      MUg/L, p = 0.055). The results of this study demonstrated that IGF system is
      altered in MSA. The degenerative process in MSA could lead to a compensatory
      increase in IGF-I and insulin in an attempt to provide additional support to
      degenerating neurons.

PMID- 20683840
TI  - Clinical spectrum of Kufor-Rakeb syndrome in the Chilean kindred with ATP13A2
      mutations.
AB  - We report the clinical features of the original Chilean family with Kufor-Rakeb
      syndrome (KRS) that led to the discovery of the ATP13A2 gene at the PARK9 locus.
      KRS is a rare juvenile-onset autosomal recessive disease characterized by
      progressive Parkinsonism, pyramidal signs, and cognitive decline in addition to
      vertical gaze palsy and facial-faucial-finger minimyoclonus. Neurological and
      neuropsychological examination during a 10-year period, videotaping,
      neuroimaging, and measurement of DNA methylation of the ATP13A2 promoter region
      were performed. The youngest 5 of 17 children of nonconsanguineous parents,
      carrying compound-heterozygous ATP13A2 mutations, had normal development until
      ages ~10 to 12 years, when school performance deteriorated and slowness,
      rigidity, and frequent falls developed. Examination revealed bradykinesia, subtle
      postural/action tremor, cogwheel rigidity, spasticity, upward gaze palsy, smooth
      pursuit with saccadic intrusions, and dementia. Additional signs included facial
      faucial-finger minimyoclonus, absent postural reflexes, visual/auditory
      hallucinations, and insomnia. Levodopa response could not be fully judged in this
      family. T2* magnetic resonance imaging sequences revealed marked diffuse
      hypointensity of the caudate (head and body) and lenticular nucleus bilaterally.
      Disease progression was slow including epilepsy, cachexia, and anarthria. Four
      affected members died after 28.5 +/- 5.5 (mean +/- SD) years of disease. Two
      heterozygous carriers, the mother and eldest sibling, showed jerky perioral
      muscle contractions and clumsiness of hand movements. There was no significant
      correlation between DNA methylation of the ATP13A2 promoter region and disease
      progression. The marked caudate and lenticular nucleus T2*-hypointensity suggests
      that KRS might belong to the family of neurodegenerative diseases associated with
      brain iron accumulation.

PMID- 20683842
TI  - Effects of diallyl sulphide in chondrocyte and cartilage in experimental
      osteoarthritis in rabbit.
AB  - Diallyl sulphide (DAS) is known for its antioxidant, anticancer and detoxifying
      properties. The aim of this study was to investigate the effect of DAS on rabbit
      articular chondrocytes and cartilage in experimental osteoarthritis (OA) induced
      by anterior cruciate ligament transection (ACLT). DAS inhibited matrix
      metalloproteinase-1 (MMP-1), MMP-3 and MMP-13 expression in interleukin-1beta (IL
      1beta)-induced chondrocytes. In an in vivo study, DAS ameliorated cartilage
      degradation as assessed by morphological and histological examination. Messenger
      RNA expression of MMP-1, MMP-3, MMP-13 and IL-1beta was inhibited by DAS in
      cartilage. In addition, DAS increased the collagen II level in cartilage. The
      results suggest that DAS may protect cartilage in the development of OA.

PMID- 20683841
TI  - Pattern separation in the dentate gyrus: a role for the CA3 backprojection.
AB  - Many theories of hippocampal function assume that area CA3 of hippocampus is
      capable of performing rapid pattern storage, as well as pattern completion when a
      partial version of a familiar pattern is presented, and that the dentate gyrus
      (DG) is a preprocessor that performs pattern separation, facilitating storage and
      recall in CA3. The latter assumption derives partly from the anatomical and
      physiological properties of DG. However, the major output of DG is from a large
      number of DG granule cells to a smaller number of CA3 pyramidal cells, which
      potentially negates the pattern separation performed in the DG. Here, we consider
      a simple CA3 network model, and consider how it might interact with a previously
      developed computational model of the DG. The resulting "standard" DG-CA3 model
      performs pattern storage and completion well, given a small set of sparse,
      randomly derived patterns representing entorhinal input to the DG and CA3.
      However, under many circumstances, the pattern separation achieved in the DG is
      not as robust in CA3, resulting in a low storage capacity for CA3, compared to
      previous mathematical estimates of the storage capacity for an autoassociative
      network of this size. We also examine an often-overlooked aspect of hippocampal
      anatomy that might increase functionality in the combined DG-CA3 model.
      Specifically, axon collaterals of CA3 pyramidal cells project "back" to the DG
      ("backprojections"), exerting inhibitory effects on granule cells that could
      potentially ensure that different subpopulations of granule cells are recruited
      to respond to similar patterns. In the model, addition of such backprojections
      improves both pattern separation and storage capacity. We also show that the DG
      CA3 model with backprojections provides a better fit to empirical data than a
      model without backprojections. Therefore, we hypothesize that CA3 backprojections
      might play an important role in hippocampal function.

PMID- 20683843
TI  - Effects of taspine on proliferation and apoptosis by regulating caspase-3
      expression and the ratio of Bax/Bcl-2 in A431 cells.

PMID- 20683844
TI  - Neuroprotective effects of a sesquiterpene lactone and flavanones from Paulownia
      tomentosa Steud. against glutamate-induced neurotoxicity in primary cultured rat
      cortical cells.
AB  - The neuroprotective effects of Paulownia tomentosa against glutamate-induced
      neurotoxicity were studied in primary cultured rat cortical cells. It was found
      that the aqueous extract of this medicinal plant significantly attenuated
      glutamate-induced toxicity. In order to clarify the mechanism(s) underlying this
      neuroprotective effect, the active fractions and components were isolated and
      identified. Five compounds were isolated as the methanol extracts from air-dried
      flowers of P. tomentosa. Isoatriplicolide tiglate exhibited significant
      neuroprotective activity against glutamate-induced toxicity at concentrations
      ranging from 1 MUM to 10 MUM, and exhibited cell viability of approximately 43
      78%. Therefore, the neuroprotective effect of P. tomentosa might be due to the
      inhibition of glutamate-induced toxicity by the sesquiterpene lactone derivative
      it contains.

PMID- 20683846
TI  - The Self-Stigma of Depression Scale (SSDS): development and psychometric
      evaluation of a new instrument.
AB  - Self-stigma may feature strongly and be detrimental for people with depression,
      but the understanding of its nature and prevalence is limited by the lack of
      psychometrically-validated measures. This study aimed to develop and validate a
      measure of self-stigma about depression. Items assessing self-stigma were
      developed from focus group discussions, and were tested and refined over three
      studies using surveys of 408 university students, 330 members of a depression
      Internet network, and 1312 members of the general Australian public. Evaluation
      involved item-level and bivariate analyses, and factor analytic procedures. Items
      performed consistently across the three surveys. The resulting Self-Stigma of
      Depression Scale (SSDS) comprised 16 items representing subscales of Shame, Self
      Blame, Social Inadequacy, and Help-Seeking Inhibition. Construct validity,
      internal consistency and test-retest reliability were satisfactory. The SSDS
      distinguishes self-stigma from perceptions of stigma by others, yields in-depth
      information about self-stigma of depression, and possesses good psychometric
      properties. It is a promising tool for the measurement of self-stigma and is
      likely to be useful in further understanding self-stigma and evaluating stigma
      interventions.

PMID- 20683845
TI  - Psychometric properties of the Quick Inventory of Depressive Symptomatology in
      adolescents.
AB  - OBJECTIVE: The clinician-rated (QIDS-C16) and self-report (QIDS-SR16) versions of
      the 16-item Quick Inventory of Depressive Symptomatology have been extensively
      examined in adult populations. This study evaluated both versions of the QIDS and
      the 17-item Children's Depressive Rating Scale - Revised (CDRS-R) in an
      adolescent outpatient sample. METHOD: Both the QIDS-C16 and QIDS-SR16 were
      completed for the adolescents. Three different methods were used to complete the
      QIDS-C16: (a) adolescents' responses to clinician interviews; (b) parents'
      responses to clinician interview; and (c) a composite score using the most
      pathological response from the two interviews. Both classical and item response
      theory methods were used. Factor analyses evaluated the dimensionality of each
      scale. RESULTS: The sample included 140 adolescent outpatients. All versions of
      the QIDS, save the parent interview, and the CDRS-R were very reliable (alpha >=
      0.8). All four versions of the QIDS are reasonably effective and unidimensional.
      The CDRS-R was clearly at least two-dimensional. The CDRS-R was the most
      discriminating among low and extremely high levels of depression. The QIDS-SR16
      was the most discriminating at moderate levels of depression. There was no
      relation between the QIDS scores and concurrent Axis III comorbidities.
      CONCLUSION: The QIDS-C16 and the QIDS-SR16 are suitable for use in adolescents.

PMID- 20683849
TI  - The METEOR study of diabetes and other metabolic disorders in patients with
      schizophrenia treated with antipsychotic drugs. I. Methodology.
AB  - Patients with schizophrenia present a two- to three-fold higher prevalence of
      diabetes, of metabolic syndrome and of cardiovascular morbidity. The reason for
      this increased prevalence may involve intrinsic vulnerability, lifestyle factors
      and iatrogenic effects of antipsychotic drugs. The objective of this
      multinational, cross-sectional, pharmacoepidemiological study was to determine
      the prevalence of diabetes, lipid disorders, obesity, hypertension and the
      metabolic syndrome in patients with schizophrenia treated with antipsychotic
      drugs. Particular attention was taken to acquire data on a wide a range as
      possible of demographic, clinical and lifestyle variables that may influence the
      risk of metabolic disorders, which were taken into account in the calculation of
      prevalence data by propensity scoring. The study included 2270 subjects from 16
      European countries, predominantly from Central and Eastern Europe. The proportion
      of subjects presenting the pathologies of interest was relatively high, ranging
      from 28% for glycaemic disorders to 70% for lipid disorders.

PMID- 20683850
TI  - Direct effects testing: a two-stage procedure to test for effect size and
      variable importance for correlated binary predictors and a binary response.
AB  - In applications such as medical statistics and genetics, we encounter situations
      where a large number of highly correlated predictors explain a response. For
      example, the response may be a disease indicator and the predictors may be
      treatment indicators or single nucleotide polymorphisms (SNPs). Constructing a
      good predictive model in such cases is well studied. Less well understood is how
      to recover the 'true sparsity pattern', that is finding which predictors have
      direct effects on the response, and indicating the statistical significance of
      the results. Restricting attention to binary predictors and response, we study
      the recovery of the true sparsity pattern using a two-stage method that separates
      establishing the presence of effects from inferring their exact relationship with
      the predictors. Simulations and a real data application demonstrate that the
      method discriminates well between associations and direct effects. Comparisons
      with lasso-based methods demonstrate favourable performance of the proposed
      method.

PMID- 20683847
TI  - Randomized trial of peginterferon alfa-2b and ribavirin for 48 or 72 weeks in
      patients with hepatitis C virus genotype 1 and slow virologic response.
AB  - The benefit of extending treatment duration with peginterferon (PEG-IFN) and
      ribavirin (RBV) from 48 weeks to 72 weeks for patients with chronic hepatitis C
      genotype 1 infection has not been well established. In this prospective,
      international, open-label, randomized, multicenter study, 1,428 treatment-naive
      patients from 133 centers were treated with PEG-IFN alfa-2b (1.5 MUg/kg/week)
      plus RBV (800-1,400 mg/day). Patients with detectable hepatitis C virus (HCV) RNA
      and a >=2-log(10) drop in HCV RNA levels at week 12 (slow responders) were
      randomized 1:1 to receive 48 weeks (n = 86) or 72 weeks (n = 73) of treatment.
      Sustained virologic response (SVR) rates were 43% in slow responders treated for
      48 weeks and 48% in slow responders treated for 72 weeks (P = 0.644). Relapse
      rates were similar in slow responders treated for 48 or 72 weeks (47% versus 33%,
      P = 0.169). The safety profile was similar in both treatment arms; serious
      adverse events leading to discontinuation of treatment were observed in 3.5% of
      slow responders treated for 48 weeks and 8.2% of those treated for 72 weeks.
      Among slow responders with a <2-log drop in HCV RNA at week 8, SVR was 39% in the
      72-week arm and 19% in the 48-week arm. CONCLUSION: These data suggest that 48
      weeks of therapy with PEG-IFN alfa-2b plus RBV (800-1,400 mg/day) should remain a
      standard-of-care treatment for treatment-naive G1 slow responders.

PMID- 20683851
TI  - A bioreactor test system to mimic the biological and mechanical environment of
      oral soft tissues and to evaluate substitutes for connective tissue grafts.
AB  - Gingival cells of the oral connective tissue are exposed to complex mechanical
      forces during mastication, speech, tooth movement and orthodontic treatments.
      Especially during wound healing following surgical procedures, internal and
      external forces may occur, creating pressure upon the newly formed tissue. This
      clinical situation has to be considered when developing biomaterials to augment
      soft tissue in the oral cavity. In order to pre-evaluate a collagen sponge
      intended to serve as a substitute for autogenous connective tissue grafts (CTGs),
      a dynamic bioreactor system was developed. Pressure and shear forces can be
      applied in this bioreactor in addition to a constant medium perfusion to cell
      material constructs. Three-dimensional volume changes and stiffness of the
      matrices were analyzed. In addition, cell responses such as cell vitality and
      extracellular matrix (ECM) production were investigated. The number of metabolic
      active cells constantly increased under fully dynamic culture conditions. The
      sponges remained elastic even after mechanical forces were applied for 14 days.
      Analysis of collagen type I and fibronectin revealed a statistically significant
      accumulation of these ECM molecules (P < 0.05-0.001) when compared to static
      cultures. An increased expression of tenascin-c, indicating tissue remodeling
      processes, was observed under dynamic conditions only. The results indicate that
      the tested in vitro cell culture system was able to mimic both the biological and
      mechanical environments of the clinical situation in a healing wound.

PMID- 20683852
TI  - Defining process design space for a hydrophobic interaction chromatography (HIC)
      purification step: application of quality by design (QbD) principles.
AB  - The concept of design space has been taking root under the quality by design
      paradigm as a foundation of in-process control strategies for biopharmaceutical
      manufacturing processes. This paper outlines the development of a design space
      for a hydrophobic interaction chromatography (HIC) process step. The design space
      included the impact of raw material lot-to-lot variability and variations in the
      feed stream from cell culture. A failure modes and effects analysis was employed
      as the basis for the process characterization exercise. During mapping of the
      process design space, the multi-dimensional combination of operational variables
      were studied to quantify the impact on process performance in terms of yield and
      product quality. Variability in resin hydrophobicity was found to have a
      significant influence on step yield and high-molecular weight aggregate clearance
      through the HIC step. A robust operating window was identified for this process
      step that enabled a higher step yield while ensuring acceptable product quality.

PMID- 20683853
TI  - Robust trypsin coating on electrospun polymer nanofibers in rigorous conditions
      and its uses for protein digestion.
AB  - An efficient protein digestion in proteomic analysis requires the stabilization
      of proteases such as trypsin. In the present work, trypsin was stabilized in the
      form of enzyme coating on electrospun polymer nanofibers (EC-TR), which
      crosslinks additional trypsin molecules onto covalently attached trypsin (CA-TR).
      EC-TR showed better stability than CA-TR in rigorous conditions, such as at high
      temperatures of 40 and 50 degrees C, in the presence of organic co-solvents, and
      at various pH's. For example, the half-lives of CA-TR and EC-TR were 1.42 and 231
      h at 40 degrees C, respectively. The improved stability of EC-TR can be explained
      by covalent linkages on the surface of trypsin molecules, which effectively
      inhibits the denaturation, autolysis, and leaching of trypsin. The protein
      digestion was performed at 40 degrees C by using both CA-TR and EC-TR in
      digesting a model protein, enolase. EC-TR showed better performance and stability
      than CA-TR by maintaining good performance of enolase digestion under recycled
      uses for a period of 1 week. In the same condition, CA-TR showed poor performance
      from the beginning and could not be used for digestion at all after a few usages.
      The enzyme coating approach is anticipated to be successfully employed not only
      for protein digestion in proteomic analysis but also for various other fields
      where the poor enzyme stability presently hampers the practical applications of
      enzymes.

PMID- 20683854
TI  - Do zebrafish Rh proteins act as dual ammonia-CO2 channels?
AB  - Transfer of the small gaseous molecules CO2 and NH3 across biological membranes,
      long thought to occur solely by simple diffusion, is now known to be facilitated
      by members of two multigene families: aquaporins (AQP) and rhesus (Rh) proteins.
      Although it is accepted that AQP1 and Rh proteins are involved in CO2 and NH3
      transfer, respectively, the idea that a single channel can exhibit selectivity
      for both gases is controversial. Indeed, studies using the same in vitro model
      (human red blood cells) have provided evidence both for and against a role for Rh
      proteins as CO2 channels. Thus, this study was initiated to provide in vivo
      evidence for a dual function of Rh proteins as ammonia and CO2 channels. Here, we
      show that in zebrafish (Danio rerio), direct ammonia-CO2 competition experiments
      in adults or translational knockdowns of Rh proteins in larvae affects both
      ammonia and CO2 excretion. These results suggest that Rh proteins in zebrafish
      may be common pathways for transport of ammonia and CO2.

PMID- 20683855
TI  - The low-dose issue and stochastic responses to endocrine disruptors.
AB  - The impact of endocrine disruptors, and specifically the low-dose issue, involves
      interdisciplinary sciences. Thus, in the past these topics have been published
      widely in the toxicology area. Owing to recent developments in biology, including
      the whole-genome reading program, the mechanisms underlying the low-dose issue
      have been clarified. These mechanisms have been found to involve stochastic and
      probabilistic receptor-mediated adverse effects induced by endocrine disruptors.
      The effects thought to be induced by low doses of endocrine-disrupting chemicals
      remain disputed, and the underlying mechanisms remain poorly understood. Three
      independent factors, each only recently identified and never before encountered
      in the history of toxicological studies, are associated with what is termed the
      'low-dose issue'. First, toxicological risk has been estimated only by
      extrapolation of adverse phenotypes from high-dose effects and thus provides no
      reliable information on low-dose effects observed at the right time under
      experimental paradigm with sufficient sensitivity. Second, toxicity is based on
      disturbances of homeostatic regulation, a largely unexplored area in toxicology.
      Third, toxicity is based on stochastic and probabilistic xenobiotic response, a
      new field of toxicology that is specifically linked to low-dose and less-frequent
      events. To resolve the low-dose issue whether it causes effects or whether
      effects observed at low-doses should be considered 'adverse'--or both, each of
      these factors needs to be addressed.

PMID- 20683856
TI  - Eight-year experience of the Cook-Swartz Doppler in free-flap operations:
      microsurgical and reexploration results with regard to a wide spectrum of
      surgeries.
AB  - BACKGROUND: Microvascular free flap has become an increasingly popular useful
      method of reconstruction over the past few decades. Minimizing failure rates in
      these operations is a primary goal in every microsurgical unit that can be
      accomplished by early recognition. METHODS: In this retrospective study, we
      tracked the admission of the implantable Doppler in the microsurgical unit (2000
      2007) and evaluated parameters measured from 473 consecutive patients who
      underwent a total of 548 microsurgical procedures (489 primary surgeries and 59
      reexplorations). The effectiveness of the Cook-Swartz Doppler (Cook Medical(r))
      was examined in juxtapose general and subspecialty's aspects: in each
      microsurgical subspecialty, we compared the overall success and failure rates of
      the group with the implantable Doppler (n = 259) with the control group monitored
      by clinical means (n = 289). We also examined the duration, outcomes, and the
      effectiveness of this device in reexploration operations. RESULTS: Overall,
      success rates were improved by using the implantable Doppler contrary to clinical
      assessment (96.14% vs. 89.27%) with a statistical significant (P < 0.005). The
      device was most effective in ENT (94.6% vs. 84%), breast reconstructive surgeries
      (97.3% vs. 82.36%), and orthopedic oncology (97.37% vs. 83.72%), whereas with
      reanimation operations and trauma/orthopedics subspecialties, it showed no
      necessity. In neurosurgery and in other/esthetic surgeries, the study was too
      small to draw definite deductions. CONCLUSIONS: We recommend the usage of the
      implantable Doppler probe as an effective monitoring system for free-flap
      surgeries, with emphasis on subspecialties where the device demonstrated better
      results than traditional monitoring methods.

PMID- 20683857
TI  - Second-order state-specific multireference Moller Plesset perturbation theory:
      Application to energy surfaces of diimide, ethylene, butadiene, and
      cyclobutadiene.
AB  - The complete active space spin-free state-specific multireference Moller-Plesset
      perturbation theory (SS-MRMPPT) based on the Rayleigh-Schrodinger expansion has
      proved to be very successful in describing electronic states of model and real
      molecular systems with predictive accuracy. The SS-MRMPPT method (which deals
      with one state while using a multiconfigurational reference wave function) is
      designed to avoid intruder effects along with a balanced description of both
      dynamic and static correlations in a size-extensive manner, which allows us to
      produce accurate potential energy surfaces (PESs) with a correct shape in bond
      breaking processes. The SS-MRMPPT method is size consistent when localized
      orbitals on each fragment are used. The intruder state(s) almost inevitably
      interfere when computing the PESs involving the breaking of genuine chemical
      bonds. In such situations, the traditional effective Hamiltonian formalism often
      goes down, so that no physically acceptable solution can be obtained. In this
      work, we continue our analysis of the SS-MRMPPT method for systems and phenomena
      that cannot be described either with the conventional single-reference approach
      or effective Hamiltonian-based traditional MR methods. In this article, we
      investigate whether the encouraging results we have obtained at the SS-MRMPPT
      level in the study of cis-trans isomerization of diimide (N2H2), ethylene (C2H4),
      and 1,3-butadiene (C4H6) carry over to the study of chemical reactions. The
      energy surfaces of the double-bond flipping interconversion of the two equivalent
      ground and two lowest singlet state structures of cyclobutadiene have also been
      studied. All results have been discussed and assessed by comparing with other
      state-of-the-art calculations and corresponding experimental data whenever
      available.

PMID- 20683858
TI  - Correction of mucopolysaccharidosis type IIIA somatic and central nervous system
      pathology by lentiviral-mediated gene transfer.
AB  - BACKGROUND: The hallmark of lysosomal storage disorders (LSDs) is microscopically
      demonstrable lysosomal distension. In mucopolysaccharidosis type IIIA (MPS IIIA),
      this occurs as a result of an inherited deficiency of the lysosomal hydrolase
      sulphamidase. Consequently, heparan sulphate, a highly sulphated
      glycosaminoglycan, accumulates primarily within the cells of the reticulo
      endothelial and monocyte-macrophage systems and, most importantly, neurones.
      Children affected by MPS IIIA experience a severe, progressive neuropathology
      that ultimately leads to death at around 15 years of age. METHODS: MPS IIIA
      pathology was addressed in a mouse model using two separate methods of
      therapeutic gene delivery. A lentiviral vector expressing murine sulphamidase was
      delivered to 6-week-old MPS IIIA affected mice either by intravenous injection,
      or by intraventricular infusion. Therapeutic outcomes were assessed 7 months
      after gene transfer. RESULTS: After intravenous gene delivery, liver sulphamidase
      was restored to approximately 30% of wild-type levels. The resultant widespread
      delivery of enzyme secreted from transduced cells to somatic tissues via the
      peripheral circulation corrected most somatic pathology. However, unlike an
      earlier study, central nervous system (CNS) pathology remained unchanged.
      Conversely, intraventricular gene delivery resulted in widespread sulphamidase
      gene delivery in (and reduced lysosomal storage throughout) the brain.
      Improvements in behaviour were observed in these mice, and interestingly,
      pathological urinary retention was prevented. CONCLUSIONS: The CNS remains the
      last major barrier to effective therapy for children affected by LSDs. The blood
      brain barrier (BBB) limits the uptake of lysosomal enzymes from the peripheral
      circulation into the CNS, making direct gene delivery to the brain a reasonable,
      albeit more challenging, therapeutic option. Future work will further assess the
      relative advantages of directly targeting the brain with somatic gene delivery
      with sulphamidase modified to increase the efficiency of transport across the
      BBB.

PMID- 20683859
TI  - The dorsal neural tube: a dynamic setting for cell fate decisions.
AB  - The dorsal neural tube first generates neural crest cells that exit the neural
      primordium following an epithelial-to-mesenchymal conversion to become
      sympathetic ganglia, Schwann cells, dorsal root sensory ganglia, and melanocytes
      of the skin. Following the end of crest emigration, the dorsal midline of the
      neural tube becomes the roof plate, a signaling center for the organization of
      dorsal neuronal cell types. Recent lineage analysis performed before the onset of
      crest delamination revealed that the dorsal tube is a highly dynamic region
      sequentially traversed by fate-restricted crest progenitors. Furthermore,
      prospective roof plate cells were shown to originate ventral to presumptive crest
      and to progressively relocate dorsalward to occupy their definitive midline
      position following crest delamination. These data raise important questions
      regarding the mechanisms of cell emigration in relation to fate acquisition, and
      suggest the possibility that spatial and/or temporal information in the dorsal
      neural tube determines initial segregation of neural crest cells into their
      derivatives. In addition, they emphasize the need to address what controls the
      end of neural crest production and consequent roof plate formation, a fundamental
      issue for understanding the separation between central and peripheral lineages
      during development of the nervous system.

PMID- 20683860
TI  - Optical waveguides based on single-crystalline organic micro-tiles.

PMID- 20683861
TI  - An anisotropic etching effect in the graphene basal plane.

PMID- 20683862
TI  - A new transparent conductor: silver nanowire film buried at the surface of a
      transparent polymer.

PMID- 20683863
TI  - Endothelial cell guidance in 3D patterned scaffolds.

PMID- 20683864
TI  - Photocurrent distribution in graphene-CdS nanowire devices.

PMID- 20683865
TI  - Signal transduction, plasma membrane calcium movements, and pigment translocation
      in freshwater shrimp chromatophores.
AB  - Crustacean color change results from the differential translocation of
      chromatophore pigments, regulated by neurosecretory peptides like red pigment
      concentrating hormone (RPCH) that, in the red ovarian chromatophores of the
      freshwater shrimp Macrobrachium olfersi, triggers pigment aggregation via
      increased cytosolic cGMP and Ca(2+) of both smooth endoplasmatic reticulum (SER)
      and extracellular origin. However, Ca(2+) movements during RPCH signaling and the
      mechanisms that regulate intracellular [Ca(2+)] are enigmatic. We investigate
      Ca(2+) transporters in the chromatophore plasma membrane and Ca(2+) movements
      that occur during RPCH signal transduction. Inhibition of the plasma membrane
      Ca(2+)-ATPase by La(3+) and indirect inhibition of the Na(+)/Ca(2+) exchanger by
      ouabain induce pigment aggregation, revealing a role for both in Ca(2+)
      extrusion. Ca(2+) channel blockade by La(3+) or Cd(2+) strongly inhibits slow
      phase RPCH-triggered aggregation during which pigments disperse spontaneously. L
      type Ca(2+) channel blockade by gabapentin markedly reduces rapid-phase
      translocation velocity; N- or P/Q-type blockade by omega-conotoxin MVIIC strongly
      inhibits RPCH-triggered aggregation and reduces velocity, effects revealing RPCH
      signaled influx of extracellular Ca(2+). Plasma membrane depolarization, induced
      by increasing external K(+) from 5 to 50 mM, produces Ca(2+)-dependent pigment
      aggregation, whereas removal of K(+) from the perfusate causes pigment
      hyperdispersion, disclosing a clear correlation between membrane depolarization
      and pigment aggregation; K(+) channel blockade by Ba(2+) also partially inhibits
      RPCH action. We suggest that, during RPCH signal transduction, Ca(2+) released
      from the SER, together with K(+) channel closure, causes chromatophore membrane
      depolarization, leading to the opening of predominantly N- and/or P/Q-type
      voltage-gated Ca(2+) channels, and a Ca(2+)/cGMP cascade, resulting in pigment
      aggregation.

PMID- 20683866
TI  - Masticatory motor pattern in the koala (Phascolarctos cinereus): a comparison of
      jaw movements in marsupial and placental herbivores.
AB  - Do closely related marsupial herbivores (Diprotodontia) conserve a common
      masticatory motor pattern or are motor patterns linked to the structure and
      function of the masticatory apparatus? We recorded the sequence and duration of
      activity of the individual jaw closing muscles during rhythmic chewing in koalas
      and then compared their motor pattern with that of their closest extant
      relatives, wombats, and their more distant marsupial relatives, macropodoids.
      These three lineages prove to have fundamentally different motor patterns and jaw
      movements during mastication. Each motor pattern represents independent
      modifications of an earlier motor pattern that was probably present in an
      ancestral diprotodontian. We show that koalas evolved a motor program that is in
      many aspects similar to that of placental herbivores with a fused mandibular
      symphysis (artiodactyls, perissodactyls, and higher primates) and almost
      identical to one artiodactyl, viz. alpacas. Anatomically, koalas are convergent
      on placental herbivores because they lost the inflected mandibular angle and
      large external part of the medial pterygoid muscle characteristic of other
      marsupials. We support the view that many different motor programs evolved for
      the control of transverse jaw movements, but identical motor programs for the
      control of transverse jaw movements can evolve independently in distantly related
      taxa.

PMID- 20683867
TI  - Systematic review and meta-analysis of steatosis as a risk factor in major
      hepatic resection (Br J Surg 2010: 97: 1331-1339).

PMID- 20683868
TI  - Fluorescent cholangiography illuminating the biliary tree during laparoscopic
      cholecystectomy (Br J Surg 2010; 97: 1369-1377).

PMID- 20683869
TI  - Accuracy of multidetector computed tomography in identifying poor prognostic
      factors in colonic cancer (Br J Surg 2010; 97: 1407-1415).

PMID- 20683871
TI  - Risk factors for portal venous thrombosis after splenectomy in patients with
      cirrhosis and portal hypertension (Br J Surg 2010; 97: 910-916).

PMID- 20683873
TI  - Chronic pain 5 years after randomized comparison of laparoscopic and Lichtenstein
      inguinal hernia repair (Br J Surg 2010; 97: 600-608).

PMID- 20683875
TI  - Case-control comparison of profundaplasty and femoropopliteal supragenicular
      bypass for peripheral arterial disease (Br J Surg 2010; 97: 344-348).

PMID- 20683877
TI  - Endoscopic resection of early gastric cancer treated by guideline and expanded
      National Cancer Centre criteria (Br J Surg 2010; 97: 868-871).

PMID- 20683879
TI  - Adverse effects of polyvinylidene fluoride-coated polypropylene mesh used for
      laparoscopic intraperitoneal onlay repair of incisional hernia (Br J Surg 2010;
      97: 1140-1145).

PMID- 20683881
TI  - Line transect surveying of arboreal monkeys: problems of group size and spread in
      a highly fragmented landscape.
AB  - Line transect surveying is a relatively rapid and efficient procedure for the
      assessment of primate populations; although the reliability of the resulting
      density estimates is affected by a number of factors, including habitat
      configuration. In this study, primate populations were surveyed at a highly
      fragmented site in northeastern Brazil, where the resident species include the
      endangered Coimbra-Filho's titi, Callicebus coimbrai, and the critically
      endangered yellow-breasted capuchin, Cebus xanthosternos. In addition to standard
      line transect surveys, data were collected on the composition and distribution of
      resident groups during playback surveys and ecological monitoring. During
      surveys, a 5.3-km trail system was walked regularly over a 7-month period,
      accumulating a total transect length of 476 km and 104 sightings of Callicebus
      and 41 of Cebus (as well as 19 records of a third primate, Callithrix jacchus).
      Data were analyzed using the DISTANCE program and the Kelker method, using the
      perpendicular distances to first animal sighted. Estimates of group density were
      highly discrepant from known values for both species; although in the case of
      Cebus, this seemed to reflect grouping patterns at the site. For Callicebus,
      population density was overestimated considerably when known group counts were
      used. Overall, there seems to be a need for a much more rigorous standardization
      of procedures, and the analysis and presentation of results, in order to
      guarantee the most reliable interpretation possible of the data. These
      considerations are especially important in the case of endangered species, such
      as those studied here.

PMID- 20683883
TI  - Effects of 1 year of daily teriparatide treatment on iliacal bone mineralization
      density distribution (BMDD) in postmenopausal osteoporotic women previously
      treated with alendronate or risedronate.
AB  - Anabolic treatment with teriparatide of postmenopausal osteoporotic patients
      previously treated with bisphosphonates is a new therapeutic approach. However,
      its effects on the bone mineralization density distribution (BMDD) are unknown.
      We studied paired transiliac bone biopsy samples taken before and after 1 year of
      treatment with recombinant human parathyroid hormone peptide 1-34 (teriparatide)
      from 16 osteoporotic women treated with either alendronate (priorALN) or
      risedronate (priorRIS) for at least 2 years and subsequently treated for 12
      months with teriparatide. Cancellous (Cn.) and cortical (Ct.) BMDD values were
      measured using quantitative backscattered electron imaging. At baseline, BMDD
      values of priorALN and priorRIS women were similar and within the normal range.
      One year of teriparatide treatment caused significant effects on the BMDD.
      Analyzing changes from baseline for each bisphosphonate group separately,
      priorALN patients revealed increases in the portion of low mineralized bone areas
      (Cn.Ca(Low) +25.9%, Ct.Ca(Low) +62.0%, both p < .05) and Ct. heterogeneity of
      mineralization (Ct.Ca(Width) +22.8%, p < .001). PriorRIS patients showed
      increased mineralization heterogeneity (Cn.Ca(Width) +14.8%, p < .05, and
      Ct.Ca(Width) +15.8%, p < .001). Analysis of the influence of the prior
      bisphosphonate treatment showed that the BMDD response to 1 year of teriparatide
      treatment did not depend on the type of prior bisphosphonate. In consequence,
      priorALN and priorRIS groups were combined. The pooled groups revealed increased
      Cn.Ca(Width) and Ct.Ca(Width) (+10.7%, p < .01, and +19.6%, p < .001,
      respectively) as well as increased Cn.Ca(Low) and Ct.Ca(Low) (+18.2%, p < .05,
      and +36.6%, p < .01, respectively). In summary, our findings indicate a
      significant effect of teriparatide on BMDD when administered subsequent to a
      bisphosphonate in agreement with teriparatide's anabolic action.

PMID- 20683884
TI  - ADAM8 enhances osteoclast precursor fusion and osteoclast formation in vitro and
      in vivo.
AB  - ADAM8 expression is increased in the interface tissue around a loosened hip
      prosthesis and in the pannus and synovium of patients with rheumatoid arthritis,
      but its potential role in these processes is unclear. ADAM8 stimulates osteoclast
      (OCL) formation, but the effects of overexpression or loss of expression of ADAM8
      in vivo and the mechanisms responsible for the effects of ADAM8 on
      osteoclastogenesis are unknown. Therefore, to determine the effects of modulating
      ADAM expression, we generated tartrate-resistant acid phosphatase (TRAP)-ADAM8
      transgenic mice that overexpress ADAM8 in the OCL lineage and ADAM8 knockout
      (ADAM8 KO) mice. TRAP-ADAM8 mice developed osteopenia and had increased numbers
      of OCL precursors that formed hypermultinucleated OCLs with an increased bone
      resorbing capacity per OCL. They also had an enhanced differentiation capacity,
      increased TRAF6 expression, and increased NF-kappaB, Erk, and Akt signaling
      compared with wild-type (WT) littermates. This increased bone-resorbing capacity
      per OCL was associated with increased levels of p-Pyk2 and p-Src activation. In
      contrast, ADAM8 KO mice did not display a bone phenotype in vivo, but unlike WT
      littermates, they did not increase RANKL production, OCL formation, or calvarial
      fibrosis in response to tumor necrosis factor alpha (TNF-alpha) in vivo. Since
      loss of ADAM8 does not inhibit basal bone remodeling but only blocks the enhanced
      OCL formation in response to TNF-alpha, these results suggest that ADAM8 may be
      an attractive therapeutic target for preventing bone destruction associated with
      inflammatory disease.

PMID- 20683885
TI  - Identification of the homeobox protein Prx1 (MHox, Prrx-1) as a regulator of
      osterix expression and mediator of tumor necrosis factor alpha action in
      osteoblast differentiation.
AB  - Tumor necrosis factor alpha (TNF-alpha) promotes bone loss and inhibits bone
      formation. Osterix (Osx, SP7) is a transcription factor required for osteoblast
      (OB) differentiation because deletion results in a cartilaginous skeleton. We
      previously described a TNF suppressor element in the Osx promoter that was used
      to isolate nuclear proteins mediating TNF inhibition of OB differentiation.
      Nuclear extracts from TNF-treated pre-OBs were incubated with the TNF suppressor
      element for protein pull-down, and tryptic fragments were analyzed by mass
      spectrometry. Chromatin immunoprecipitation (ChIP) assay confirmed eight bound
      transcription factors. One protein, the paired related homeobox protein (Prx1),
      had been shown previously to have a critical role in limb bud formation and
      skeletal patterning. PCR revealed Prx1 expression in primary stromal cells
      (MSCs), C3H10T1/2 cells, and MC3T3 preosteoblasts. TNF stimulated a 14-fold
      increase in mRNA for Prx1, rapid cell accumulation in MC3T3 cells, and expression
      in periosteal and trabecular lining cells in vivo. Transient expression of Prx
      inhibited transcription of Osx and RUNX2. Expression of the Prx1b isoform or Prx2
      decreased Osx and RUNX2 mRNA and OB differentiation in preosteoblasts. Silencing
      of Prx1 with siRNA abrogated TNF suppression of Osx mRNA and increased basal Osx
      expression. Electrophoretic mobility shift revealed Prx1b as the preferred
      isoform binding the Osx promoter. These results identify the homeobox protein
      Prx1 as an obligate mediator of TNF inhibition of Osx and differentiation of OB
      progenitors. Activation of Prx1 by TNF may contribute to reduced bone formation
      in inflammatory arthritis, menopause, and aging.

PMID- 20683886
TI  - The promise and realities of comparative effectiveness research.
AB  - Comparative Effectiveness Research (CER) has been given a broad and ambitious
      mandate. Will it be able to deliver the multifaceted and granular comparative
      information that it has been tasked with developing? After a discussion of the
      general conditions for the feasibility of CER, we focus our attention on one of
      the most challenging areas: the evaluation of diagnostic tests and biomarkers.

PMID- 20683887
TI  - The historical and moral imperatives of comparative effectiveness research.

PMID- 20683888
TI  - What is evidence?
AB  - The assumption that comparative effectiveness research will provide timely,
      relevant evidence rests on changing the current framework for assembling
      evidence. In this commentary, we provide the background of how coverage decisions
      for new medical technologies are currently made in the United States. We focus on
      the statistical issues regarding how to use the ensemble of information for
      inferring comparative effectiveness. It is clear a paradigm shift in how clinical
      information is integrated in real-world settings to establish effectiveness is
      required.

PMID- 20683889
TI  - Comments on 'Comparative effectiveness research: Policy context, methods
      development and research infrastructure'.

PMID- 20683890
TI  - On the limitations of comparative effectiveness research.

PMID- 20683892
TI  - Discovery of complex pathways from observational data.
AB  - Unraveling complex interactions has been a challenge in epidemiologic research.
      We introduce a pathway modeling framework that discovers plausible pathways from
      observational data, and allows estimation of both the net effect of the pathway
      and the types of interactions occurring among genetic or environmental risk
      factors. Each discovered pathway structure links combinations of observed
      variables through intermediate latent nodes to a final node, the outcome.
      Biologic knowledge can be readily applied in this framework as a prior on pathway
      structure to give preference to more biologically plausible models, thereby
      providing more precise estimation of Bayes factors for pathways of greatest
      interest by Markov Chain Monte Carlo (MCMC) methods.Data were simulated for
      binary inputs of which only a subset was involved in different pathway
      topologies. Our algorithm was then used to recover the pathway from the simulated
      data. The posterior distributions of inputs, pairwise and higher-order
      interactions, and topologies were obtained by MCMC methods. The evidence in favor
      of a particular pathway or interaction was summarized using Bayes factors. Our
      method can correctly identify the risk factors and interactions involved in the
      simulated pathway. We apply our framework to an asthma case-control data set with
      polymorphisms in 12 genes.

PMID- 20683893
TI  - Space-time latent component modeling of geo-referenced health data.
AB  - Latent structure models have been proposed in many applications. For space-time
      health data it is often important to be able to find the underlying trends in
      time, which are supported by subsets of small areas. Latent structure modeling is
      one such approach to this analysis. This paper presents a mixture-based approach
      that can be applied to component selection. The analysis of a Georgia ambulatory
      asthma county-level data set is presented and a simulation-based evaluation is
      made.

PMID- 20683894
TI  - Using Testlet Response Theory to analyze data from a survey of attitude change
      among breast cancer survivors.
AB  - In this paper we examine alternative measurement models for fitting data from
      health surveys. We show why a testlet-based latent trait model that includes
      covariate information, embedded within a fully Bayesian framework, can allow
      multiple simultaneous inferences and aid interpretation. We illustrate our
      approach with a survey of breast cancer survivors that reveals how the attitudes
      of those patients change after diagnosis toward a focus on appreciating the here
      and-now, and away from consideration of longer-term goals. Using the covariate
      information, we also show the extent to which individual-level variables such as
      race, age and Tamoxifen treatment are related to a patient's change in
      attitude.The major contribution of this research is to demonstrate the use of a
      hierarchical Bayesian IRT model with covariates in this application area; hence a
      novel case study, and one that is certainly closely aligned with but distinct
      from the educational testing applications that have made IRT the dominant test
      scoring model.

PMID- 20683895
TI  - Estimation of overall survival in an 'illness-death' model with application to
      the vertical transmission of HIV-1.
AB  - We derive a nonparametric maximum likelihood estimate of the overall survival
      distribution in an illness-death model from interval censored observations with
      unknown status of the nonfatal event. This expanded model is applied to the re
      analysis of data from a randomized trial where infants, born to women infected
      with HIV-1 that were randomly assigned to breastfeeding or counseling for formula
      feeding, were followed for 24 months for HIV-1 positivity, HIV-1-free survival,
      and overall survival. HIV-1 positivity, assessed by postpartum venous blood
      tests, is the interval censored nonfatal event, and HIV-1 positivity status is
      unknown for a subset of infants due to periodic assessment. The analysis
      demonstrates that estimation of the overall and the pre- and post-nonfatal event
      survival distributions with the proposed methods provide novel insights into how
      overall survival is influenced by the occurrence of the nonfatal event. More
      generally, it suggests the usefulness of this expanded illness-death model when
      evaluating composite endpoints as potential surrogates for overall survival in a
      given disease setting.

PMID- 20683896
TI  - Method of balanced adjustment in testing co-primary endpoints.
AB  - In a clinical trial, if there are three or more co-primary endpoints, the type II
      error could increase depending on the correlation among the endpoints and their
      treatment effect sizes. To keep the type II error under control one may have to
      consider larger sample sizes. However, in cases where treatment effect size of at
      least one of the endpoints is likely to be small, the required sample size
      estimates can exceed reasonable bounds. Patel (1991) proposed an approach that
      adjusts the significance level for testing each primary endpoint based on the
      idea of restricting the null space. In Chuang-Stein et al. (2007), the upward
      adjustment to the significance levels is based on controlling an average type I
      error rate. In the scenario that statistical significance of each individual
      hypothesis is not required, we introduce a compromise testing approach in which
      the significance level for a co-primary endpoint is adjusted upward only if the
      treatment shows high significance in one (or more than one) of the remaining co
      primary endpoints. The adjustment depends on the correlation among the endpoints:
      larger adjustment is needed for cases of smaller correlation. The method is
      applicable for the scenario where the null space is restricted. Our testing
      approach controls maximum joint false positive rate over the restricted null
      space.

PMID- 20683897
TI  - Mistake on quantifying the indirect treatment effect via surrogate markers by Y.
      Qu and M. Case Statistics in Medicine 2006; 25:223-231.

PMID- 20683899
TI  - Sustained LFA-1 cluster formation in the immune synapse requires the combined
      activities of L-plastin and calmodulin.
AB  - Formation of immune synapses (IS) between T cells and APC requires multiple
      rearrangements in the actin cytoskeleton and selective receptor accumulation in
      supramolecular activation clusters (SMAC). The inner cluster (central SMAC)
      contains the TCR/CD3 complex. The outer cluster (peripheral SMAC) contains the
      integrin LFA-1 and Talin. Molecular mechanisms selectively stabilizing receptors
      in the IS remained largely unknown. Here, we demonstrate that sustained LFA-1
      clustering in the IS is a consequence of the combined activities of the actin
      bundling protein L-plastin (LPL) and calmodulin. Thus, upon antigen-recognition
      of T cells, LPL accumulated predominantly in the peripheral SMAC. siRNA-mediated
      knock-down of LPL led to a failure of LFA-1 and Talin redistribution - however,
      not TCR/CD3 relocalization - into the IS. As a result of this LPL knock-down, the
      T-cell/APC interface became smaller over time and T-cell proliferation was
      inhibited. Importantly, binding of calmodulin to LPL was required for the
      maintenance of LPL in the IS and consequently inhibition of calmodulin also
      prevented stable accumulation of LFA-1 and Talin, but not CD3, in the IS.

PMID- 20683900
TI  - Dichotomy between factors inducing the immunosuppressive enzyme IL-4-induced gene
      1 (IL4I1) in B lymphocytes and mononuclear phagocytes.
AB  - MPhi and DC are key elements in the control of tissue homeostasis and response to
      insult. In this work, we demonstrate that MPhi and DC are the major producers of
      the phenylalanine catabolizing enzyme IL-4-induced gene 1 (IL4I1) under
      inflammatory conditions. IL4I1 was first described in B cells, which indeed can
      produce IL4I1 in vitro, although at much lower levels. In vivo, IL4I1 is highly
      expressed by MPhi and DC of Th1 granulomas (sarcoidosis, tuberculosis) but poorly
      detected in Th2 granulomas (schistosomiasis). In vitro, expression of the enzyme
      is induced in mononuclear phagocytes by various pro-inflammatory stimuli through
      the activation of the transcription factors NF-kappaB and/or STAT1. B cells also
      express IL4I1 in response to NF-kappaB-activating stimuli such as CD40L; however,
      in contrast to myeloid cells, B cells are insensitive to IFN-gamma but respond to
      stimulation of the IL-4/STAT6 axis. As we show that the expression of IL4I1 by a
      monocytic cell line inhibits T-cell proliferation and production of IFN-gamma and
      inflammatory cytokines, we propose that IL4I1 participates in the downregulation
      of Th1 inflammation in vivo.

PMID- 20683901
TI  - A live Leishmania major vaccine containing CpG motifs induces the de novo
      generation of Th17 cells in C57BL/6 mice.
AB  - Cutaneous leishmaniasis produces open sores that lead to scarring and
      disfiguration. We have reported that vaccination of C57BL/6 mice with live
      Leishmania major plus CpG DNA (Lm/CpG) prevents lesion development and provides
      long-term immunity. Our current study aims to characterize the components of the
      adaptive immune response that are unique to Lm/CpG. We find that this vaccine
      enhances the proliferation of CD4(+) Th17 cells, which contrasts with the highly
      polarized Th1 response caused by L. major alone; the Th17 response is dependent
      upon release of vaccine-induced IL-6. Neutralization of IFN-gamma and, in
      particular, IL-17 caused increased parasite burdens in Lm/CpG-vaccinated mice. IL
      17R-deficient Lm/CpG-vaccinated mice develop lesions, and display decreased IL-17
      and IFN-gamma, despite normal IL-12, production. Neutrophil accumulation is also
      decreased in the IL-17R-deficient Lm/CpG-vaccinated mice but Treg numbers are
      augmented. Our data demonstrate that activation of immune cells through CpG DNA,
      in the presence of live L. major, causes the specific induction of Th17 cells,
      which enhances the development of a protective cellular immunity against the
      parasite. Our study also demonstrates that vaccines combining live pathogens with
      immunomodulatory molecules may strikingly modify the natural immune response to
      infection in an alternative manner to that induced by killed or subunit vaccines.

PMID- 20683902
TI  - Osteoblasts are a major source of inflammatory cytokines in the tumor
      microenvironment of bone metastatic breast cancer.
AB  - Metastatic breast cancer cells co-opt the cells of the bone to increase their
      production of inflammatory cytokines. Here, we sought to identify key cytokines
      expressed by osteoblasts in vitro and in vivo in the presence of MDA-MB-231
      metastatic breast cancer cells, including a bone-seeking variant. We hypothesized
      that osteoblast-derived cytokines increase in the presence of metastatic breast
      cancer cell conditioned medium (CM), act as chemoattractants for cancer cells,
      and enhance osteoclast formation. We detected increases in the concentrations of
      osteoblast-derived IL-6, MCP-1, VEGF, MIP-2, and KC in vitro in culture
      supernatants from MC3T3-E1 cells in the presence of metastatic breast cancer cell
      CM and from cancer-bearing femurs ex vivo. A comparison of cancer cell- and
      osteoblast-derived cytokines revealed that while breast cancer cells expressed
      the same or equivalent cytokines as the osteoblasts, the breast cancer cells only
      produced picogram quantities of MCP-1; osteoblasts expressed nanogram amounts.
      Bone-derived MCP-1 increased in the proximal metaphysis, an area where breast
      cancer cells preferentially trafficked following intracardiac inoculation in
      athymic mice. An MDA-MB-231 bone-seeking variant was not different from parental
      lines. Osteoblast CM was a potent chemoattractant for metastatic breast cancer
      cells. Furthermore, culture supernatants of osteoblasts treated with breast
      cancer cell CM enhanced osteoclast formation. These findings suggest that bone
      metastatic breast cancer cells utilize osteoblast-derived cytokines to facilitate
      breast cancer cell colonization and survival upon arrival in the bone
      microenvironment.

PMID- 20683903
TI  - Mangiferin attenuates osteoclastogenesis, bone resorption, and RANKL-induced
      activation of NF-kappaB and ERK.
AB  - Osteolytic bone diseases such as osteoporosis have a common pathological feature
      in which osteoclastic bone resorption outstrips bone synthesis. Osteoclast
      formation and activation are regulated by receptor activator of nuclear factor
      kappaB ligand (RANKL). The induction of RANKL-signaling pathways occurs following
      the interaction of RANKL to its cognate receptor, RANK. This specific binding
      drives the activation of downstream signaling pathways; which ultimately induce
      the formation and activation of osteoclasts. In this study, we showed that a
      natural immunomodulator, mangiferin, inhibits osteoclast formation and bone
      resorption by attenuating RANKL-induced signaling. Mangiferin diminished the
      expression of osteoclast marker genes, including cathepsin K, calcitonin
      receptor, DC-STAMP, and V-ATPase d2. Mechanistic studies revealed that mangiferin
      inhibits RANKL-induced activation of NF-kappaB, concomitant with the inhibition
      of IkappaB-alpha degradation, and p65 nuclear translocation. In addition,
      mangiferin also exhibited an inhibitory effect on RANKL-induced ERK
      phosphorylation. Collectively, our data demonstrates that mangiferin exhibits
      anti-resorptive properties, suggesting the potential application of mangiferin
      for the treatment and prevention of bone diseases involving excessive
      osteoclastic bone resorption.

PMID- 20683904
TI  - Demethyl fruticulin A (SCO-1) causes apoptosis by inducing reactive oxygen
      species in mitochondria.
AB  - Demethyl fruticulin A (SCO-1) is a compound found in Salvia corrugata leaves. SCO
      1 was reported to induce anoikis in cell lines via the membrane scavenging
      receptor CD36. However, experiments performed with cells lacking CD36 showed that
      SCO-1 was able to induce apoptosis also via alternative pathways. To gain some
      insight into the biological processes elicited by this compound, we undertook an
      unbiased genomic approach. Upon exposure of glioblastoma tumor initiating cells
      (GBM TICs) to SCO-1 for 24 h, we observed a deregulation of the genes belonging
      to the glutathione metabolism pathway and of those belonging to the biological
      processes related to the response to stress and to chemical stimulus. On this
      basis, we hypothesized that the SCO-1 killing effect could result from the
      induction of reactive oxygen species (ROS) in the mitochondria. This hypothesis
      was confirmed by flow cytometry using MitoSOX, a mitochondria-selective
      fluorescent reporter of ROS, and by the ability of N-acetyl cysteine (NAC) to
      inhibit apoptosis when co-administered with SOC-1 to the GBM TICs. We further
      show that NAC also protects other cell types such as HeLa, MG-63, and COS-7 from
      apoptosis. We therefore propose that ROS production is the major molecular
      mechanism responsible for the pro-apoptotic effect induced by SCO-1.
      Consequently, SCO-1 may have a potential therapeutic value, which deserves
      further investigation in animal models.

PMID- 20683907
TI  - A retrospective cohort study of mortality among children with birth defects in
      New York State, 1983-2006.
AB  - BACKGROUND: Birth defects, which occur in about 3% of live births in the United
      States each year, have remained the leading cause of infant mortality, although
      the infant mortality rate in the United States has decreased significantly over
      the past decades. The objective of this study was to conduct a retrospective
      cohort study with long-term follow-up of the children in New York State
      Congenital Malformations Registry (CMR) for up to 24 years on their mortality
      status to evaluate the mortality risk of children with birth defects by age at
      death, birth defect category and other possible contributing factors. METHODS:
      Children born in 1983-2006 with reportable birth defects were included in the
      study cohort. A sub-cohort was also constructed containing children born in 1983
      2006 with selected major birth defects that are relatively severe congenital
      conditions identified at birth. New York State live births in 1983-2006 were used
      as the comparison population. The deaths among the study cohort were identified
      through linking CMR cases to the death certificate files. A Poisson regression
      model was used to calculate mortality rate ratios (mortality risk) adjusting for
      selected infant and maternal risk factors. RESULTS: Compared to children without
      birth defects, the overall mortality risk was 6.7 times higher for children with
      any of the reportable birth defects and 23.6 times higher for children with
      selected major birth defects. The mortality risk decreased with increasing age of
      children. The top 5 most significantly high mortality risks were found among
      infants in neonatal period with anencephaly (RR = 200.5, 95% CI:180.6-222.5) and
      renal agenesis/dysgenesis (RR = 69.5, 95% CI:64.2-75.2), and among children aged
      1-2 years with Trisomy 18 (RR = 206.4, 95% CI:28.5-331.6), Trisomy 13 (RR =
      157.3, 95% CI:83.5-296.4), and hypoplastic left heart (RR = 161.5, 95% CI:20.1
      217.2). Low birth weight and gestational age, multiple malformations and high
      lethality of anomalies involved were the major contributors to the high risk of
      mortality among children with selected major birth defects compared to those
      without birth defects. CONCLUSIONS: Using the state-wide, population-based birth
      defects surveillance data to conduct a long-term follow-up of a large cohort of
      New York children, we were able to examine mortality and survival experience of
      the affected children during infancy and childhood period by individual birth
      defects of interest. As expected, children born with birth defects had a higher
      risk of mortality compared to children without birth defects. The magnitude of
      the risk varied by children's age, birth and maternal characteristics and the
      lethality of the specific birth defects involved.

PMID- 20683905
TI  - Association of folate receptor (FOLR1, FOLR2, FOLR3) and reduced folate carrier
      (SLC19A1) genes with meningomyelocele.
AB  - BACKGROUND: Meningomyelocele (MM) results from lack of closure of the neural tube
      during embryologic development. Periconceptional folic acid supplementation is a
      modifier of MM risk in humans, leading toan interest in the folate transport
      genes as potential candidates for association to MM. METHODS: This study used the
      SNPlex Genotyping (ABI, Foster City, CA) platform to genotype 20 single
      polymorphic variants across the folate receptor genes (FOLR1, FOLR2, FOLR3) and
      the folate carrier gene (SLC19A1) to assess their association to MM. The study
      population included 329 trio and 281 duo families. Only cases with MM were
      included. Genetic association was assessed using the transmission disequilibrium
      test in PLINK. RESULTS: A variant in the FOLR2 gene (rs13908), three linked
      variants in the FOLR3 gene (rs7925545, rs7926875, rs7926987), and two variants in
      the SLC19A1 gene (rs1888530 and rs3788200) were statistically significant for
      association to MM in our population. CONCLUSION: This study involved the analyses
      of selected single nucleotide polymorphisms across the folate receptor genes and
      the folate carrier gene in a large population sample. It provided evidence that
      the rare alleles of specific single nucleotide polymorphisms within these genes
      appear to be statistically significant for association to MM in the patient
      population that was tested.

PMID- 20683908
TI  - Protein changes in macrophages induced by plasma from rats exposed to 35 GHz
      millimeter waves.
AB  - A macrophage assay and proteomic screening were used to investigate the
      biological activity of soluble factors in the plasma of millimeter wave-exposed
      rats. NR8383 rat macrophages were incubated for 24 h with 10% plasma from male
      Sprague-Dawley rats that had been exposed to sham conditions, or exposed to 42 
      degrees C environmental heat or 35 GHz millimeter waves at 75 mW/cm2 until core
      temperature reached 41.0  degrees C. Two-dimensional polyacrylamide gel
      electrophoresis, image analysis, and Western blotting were used to analyze
      approximately 600 protein spots in the cell lysates for changes in protein
      abundance and levels of 3-nitrotyrosine, a marker of macrophage stimulation.
      Proteins of interest were identified using peptide mass fingerprinting. Compared
      to plasma from sham-exposed rats, plasma from environmental heat- or millimeter
      wave-exposed rats increased the expression of 11 proteins, and levels of 3
      nitrotyrosine in seven proteins, in the NR8383 cells. These altered proteins are
      associated with inflammation, oxidative stress, and energy metabolism. Findings
      of this study indicate both environmental heat and 35 GHz millimeter wave
      exposure elicit the release of macrophage-activating mediators into the plasma of
      rats.

PMID- 20683909
TI  - Effect of static magnetic fields on the budding of yeast cells.
AB  - The effect of static magnetic fields on the budding of single yeast cells was
      investigated using a magnetic circuit that was capable of generating a strong
      magnetic field (2.93 T) and gradient (6100 T2  m-1). Saccharomyces cerevisiae
      yeast cells were grown in an aqueous YPD agar in a silica capillary under either
      a homogeneous or inhomogeneous static magnetic field. Although the size of
      budding yeast cells was only slightly affected by the magnetic fields after 4 h,
      the budding angle was clearly affected by the direction of the homogeneous and
      inhomogeneous magnetic fields. In the homogeneous magnetic field, the budding
      direction of daughter yeast cells was mainly oriented in the direction of
      magnetic field B. However, when subjected to the inhomogeneous magnetic field,
      the daughter yeast cells tended to bud along the axis of capillary flow in
      regions where the magnetic gradient, estimated by B(dB/dx), were high. Based on
      the present experimental results, the possible mechanism for the magnetic effect
      on the budding direction of daughter yeast cells is theoretically discussed.

PMID- 20683910
TI  - Assessment of the exposure to WLAN frequencies of a head model with a cochlear
      implant.
AB  - In the last few years, significant developments have taken place in the field of
      Wireless Local Area Networks (WLAN), and the popularity of portable devices
      supporting Wireless Fidelity (Wi-Fi) is continuously growing. At the same time,
      the number of Active Implanted Medical Devices (AIMD) being placed in patients is
      widely increasing and among them, cochlear implants (CI) are becoming a common
      aid. The goal of this study is to investigate the effect on the electromagnetic
      field distribution and the specific absorption rate (SAR) due to the presence of
      a CI in a head model during far-field exposure to Wi-Fi frequencies. The head
      model was obtained by image segmentation, the implant was modelled as a geometric
      structure, and the exposure sources were modelled as a uniform plane wave (power
      density = 10 W/m(2)) at 2.4, 5.2 and 5.8 GHz. Vertical and horizontal
      polarizations were simulated. Conditions with and without CI were compared. The
      findings of that are: (1) local differences in the field distribution close to
      the CI, comparing the head models with or without the CI; (2) higher field
      strength and point SAR value in the cochlear region very close to the CI; (3)
      negligible differences in the field strength and point SAR value in the cochlear
      region far from the CI; (4) negligible variations in the average SAR values in
      the cochlea and head due to the presence of the CI. The results of this study
      conclude that insertion of a CI brings moderate localized differences in the E, H
      and point SAR distribution when evaluated close to the electrode array in the
      cochlea, while negligible differences are found in the average SAR values both in
      the cochlea and head, independent of frequency and wave polarization.

PMID- 20683911
TI  - Up-regulation of endoplasmic reticulum stress-related genes during the early
      phase of treatment of cultured cortical neurons by the proteasomal inhibitor
      lactacystin.
AB  - Inhibition of proteasome degradation pathway has been implicated in neuronal cell
      death leading to neurodegenerative diseases such as Parkinson's disease and
      Alzheimer's disease. We and others demonstrated that treatment of cortical
      neurons with the proteasomal inhibitor lactacystin leads to apoptosis. We
      discovered by microarray analysis that lactacystin treatment modulates the
      expression of both potentially neuroprotective as well as pro-apoptotic genes in
      neurons. However, the significance of the genes which upon transcriptional
      modulation contributed to proteasomal inhibition-induced apoptosis, remained
      unidentified. By employing microarray analysis to decipher the time-dependent
      changes in transcription of these genes in cultured cortical neurons, we
      discovered different groups of genes were transcriptionally regulated in the
      early and late phase of lactacystin-induced cell death. In the early phase,
      several neuroprotective genes such as those encoding the proteasome subunits and
      ubiquitin-associated enzymes, as well as the heat-shock proteins (HSP) were up
      regulated. However, the pro-apoptotic endoplasmic reticulum (ER) stress
      associated genes were also up-regulated at the early phase of lactacystin-induced
      neuronal cell death. In the late phase, genes encoding antioxidants and calcium
      binding proteins were up-regulated while those associated with cholesterol
      biosynthesis were down-regulated. The data suggest that ER stress may participate
      in mediating the apoptotic responses induced by proteasomal inhibition. The up
      regulation of the neuroprotective antioxidant genes and calcium-binding protein
      genes and down-regulation of the cholesterol biosynthesis genes in the later
      phase are likely consequences of stimulation of the pro-apoptotic signaling
      pathways in the early phase of lactacystin treatment.

PMID- 20683912
TI  - Glutaminolysis and glycolysis regulation by troglitazone in breast cancer cells:
      Relationship to mitochondrial membrane potential.
AB  - We studied the roles of glycolysis and glutaminolysis following an acute
      reduction in mitochondrial membrane potential (Psi(m)) induced by the
      thiazolidinedione troglitazone (TRO) and compared the responses with CCCP-induced
      depolarization in breast cancer derived MCF-7 and MDA-MB-231 cells as well as in
      the MCF-10A normal breast cell line. TRO and CCCP both acutely reduced Psi(m) but
      after 24 h TRO-treated cells had restored Psi(m) associated with both increased
      glycolysis and glutaminolysis. In contrast, CCCP-treated cells exhibited only a
      partial restoration of Psi(m) associated with increased glycolysis but decreased
      glutaminolysis. TRO-induced glutaminolysis was coupled to increased ammonium (GDH
      flux) and decreased alanine production (ALT flux) in all three cell lines. Both
      cancer cell lines exhibited a higher spontaneous GDH/ALT flux than the normal
      breast cell line associated with a reduced keto-acid pool. TRO's effect on
      GDH/ALT fluxes and mitochondrial keto-acid pool homeostasis was additive with
      glucose withdrawal suggesting limited intramitochondrial pyruvate availability.
      The TRO-induced acceleration in GDH flux supplies substrate for Complex I
      contributing to the restoration of Psi(m) as well as Krebs cycle intermediates
      for biosynthesis. Inhibiting mitochondrial proton ATPase with oligomycin or
      nullifying the proton gradient with CCCP prevented both the TRO-induced recovery
      of Psi(m) and accelerated GDH flux but restored ALT flux consonant with important
      roles for proton pumping in regulating GDH flux and Psi(m) recovery. Blocking
      enhanced GDH flux reduced DNA synthesis consistent with glutaminolysis via GDH
      playing an important biosynthetic role in tumorigenesis.

PMID- 20683913
TI  - The effect of hepatocyte growth factor on the initial stages of mouse follicle
      development.
AB  - Interactions between theca and granulosa cells of the follicle are critical for
      the coordination of ovarian follicle development. The cell-cell interactions are
      mediated through the local production and actions of a variety of factors. The
      current study is designed to investigate the expression of Hgf and its receptor,
      c-Met, in the mouse ovary during in vivo folliculogenesis. We found that Hgf and
      c-Met mRNAs were already expressed in 2-day-old ovaries, and that, while c-Met
      levels remained constant until 22-day-old, Hgf levels slightly but not
      significantly increased with age. The expression of Hgf mRNA in
      theca/interstitial cells was higher than in granulosa cells in 22-day-old
      ovaries. Immunohistochemistry analysis confirmed the expression pattern
      demonstrated by RT-PCR. We investigated the role of hepatocyte growth factor
      (HGF) at the beginning of mouse folliculogenesis and its possible interaction
      with kit ligand (KL). Interestingly, both KL and HGF were able to increase the
      expression of each other, creating a positive feedback loop. In the presence of
      HGF, we observed an increase of granulosa cell proliferation and an increase in
      the number of pre-antral and early antral follicles in ovary organ cultures. We
      also observed a significant increase in the diameters of follicles in individual
      follicle cultures. Moreover, HGF stimulated the expression of the FSH receptors,
      both in the whole ovary and in isolated pre-antral follicle cultures. Based on
      the data presented, we concluded that HGF exerts multiple levels of control over
      follicular cell functions, which collectively enable the progression of
      follicular development.

PMID- 20683914
TI  - Bax is essential for Drp1-mediated mitochondrial fission but not for
      mitochondrial outer membrane permeabilization caused by photodynamic therapy.
AB  - Bcl-2 family proteins are critical for the regulation of apoptosis, with the pro
      apoptotic members Bax essential for the release of cytochrome c from mitochondria
      in many instances. However, we found that Bax was activated after mitochondrial
      depolarization and the completion of cytochrome c release induced by photodynamic
      therapy (PDT) with the photosensitizer Photofrin in human lung adenocarcinoma
      cells (ASTC-a-1). Besides, knockdown of Bax expression by gene silencing had no
      effect on mitochondrial depolarization and cytochrome c release, indicating that
      Bax makes no contribution to mitochondrial outer membrane permeabilization (MOMP)
      following PDT. Further study revealed that Bax knockdown only slowed down the
      speed of cell death induced by PDT, indicating that Bax is not essential for PDT
      induced apoptosis. The fact that Bax knockdown totally inhibited the
      mitochondrial accumulation of dynamin-related protein (Drp1) and Drp1 knockdown
      attenuated cell apoptosis suggest that Bax can promote PDT-induced apoptosis
      through promoting Drp1 activation. Besides, Drp1 knockdown also failed to inhibit
      PDT-induced cell death finally, indicating that Bax-mediated Drp1's mitochondrial
      translocation is not essential for PDT-induced cell apoptosis. On the other hand,
      we found that protein kinase Cdelta (PKCdelta), Bim L and glycogen synthase
      kinase 3beta (GSK3beta) were activated upon PDT treatment and might contribute to
      the activation of Bax under the condition. Taken together, Bax activation is not
      essential for MOMP but essential for Drp1-mediated mitochondrial fission during
      the apoptosis caused by Photofrin-PDT.

PMID- 20683915
TI  - Down-regulation of Orai3 arrests cell-cycle progression and induces apoptosis in
      breast cancer cells but not in normal breast epithelial cells.
AB  - Breast cancer (BC) is the leading cancer in the world in terms of incidence and
      mortality in women. However, the mechanism by which BC develops remains largely
      unknown. The increase in cytosolic free Ca(2+) can result in different
      physiological changes including cell growth and death. Orai isoforms are highly
      Ca(2+) selective channels. In the present study, we analyzed Orai3 expression in
      normal and cancerous breast tissue samples, and its role in MCF-7 BC and normal
      MCF-10A mammary epithelial cell lines. We found that the expression of Orai3
      mRNAs was higher in BC tissues and MCF-7 cells than in normal tissues and MCF-10A
      cells. Down-regulation of Orai3 by siRNA inhibited MCF-7 cell proliferation and
      arrested cell cycle at G1 phase. This phenomenon is associated with a reduction
      in CDKs 4/2 (cyclin-dependent kinases) and cyclins E and D1 expression and an
      accumulation of p21(Waf1/Cip1) (a cyclin-dependent kinase inhibitor) and p53 (a
      tumor-suppressing protein). Orai3 was also involved in MCF-7 cell survival.
      Furthermore, Orai3 mediated Ca(2+) entry and contributed to intracellular calcium
      concentration ([Ca(2+)](i)). In MCF-10A cells, silencing Orai3 failed to modify
      [Ca(2+)](i), cell proliferation, cell-cycle progression, cyclins (D1, E), CDKs
      (4, 2), and p21(Waf1/Cip1) expression. Our results provide strong evidence for a
      significant effect of Orai3 on BC cell growth in vitro and show that this effect
      is associated with the induction of cell cycle and apoptosis resistance. Our
      study highlights a possible role of Orai3 as therapeutic target in BC therapy.

PMID- 20683916
TI  - High fluence low-power laser irradiation induces apoptosis via inactivation of
      Akt/GSK3beta signaling pathway.
AB  - High fluence low-power laser irradiation (HF-LPLI) is a newly discovered stimulus
      through generating reactive oxygen species (ROS) to trigger cell apoptosis.
      Activation of glycogen synthase kinase 3beta (GSK3beta) is proved to be involved
      in intrinsic apoptotic pathways under various stimuli. However, whether the
      proapoptotic factor GSK3beta participates in HF-LPLI-induced apoptosis has not
      been elucidated. Therefore, in the present study, we investigated the involvement
      of GSK3beta in apoptosis under HF-LPLI treatment (120 J/cm2, 633 nm). We found
      that GSK3beta activation could promote HF-LPLI-induced apoptosis, which could be
      prevented by lithium chloride (a selective inhibitor of GSK3beta) exposure or by
      GSK3beta-KD (a dominant-negative GSK3beta) overexpression. We also found that the
      activation of GSK3beta by HF-LPLI was due to the inactivation of protein kinase B
      (Akt), a widely reported and important upstream negative regulator of GSK3beta,
      indicating the existence and inactivation of Akt/GSK3beta signaling pathway.
      Moreover, the inactivation of Akt/GSK3beta pathway depended on the fluence of HF
      LPLI treatment. Furthermore, vitamin c, a ROS scavenger, completely prevented the
      inactivation of Akt/GSK3beta pathway, indicating ROS generation was crucial for
      the inactivation. In addition, GSK3beta promoted Bax activation by down
      regulating Mcl-1 upon HF-LPLI treatment. Taken together, we have identified a new
      and important proapoptotic signaling pathway that is consisted of Akt/GSK3beta
      inactivation for HF-LPLI stimulation. Our research will extend the knowledge into
      the biological mechanisms induced by LPLI.

PMID- 20683917
TI  - Isolation and characterization of dendrimers with precise numbers of functional
      groups.

PMID- 20683918
TI  - Dynamic microcrystal assembly by nitroxide exchange reactions.

PMID- 20683919
TI  - Arylation of alpha-chiral ketones by palladium-catalyzed cross-coupling reactions
      of tosylhydrazones with aryl halides.

PMID- 20683920
TI  - First-principles calculation of electronic structure of V-doped anatase TiO2.
AB  - The energetic and electronic structures of V-doped anatase TiO(2) have been
      investigated systematically by the GGA+U approach, including replacement of Ti by
      V in the absence and presence of oxygen vacancies and the presence of an
      interstitial site. It was found that V should exist as a V(4+) ion in the
      replacement of Ti in the anatase lattice, the electron transitions of which to
      the conduction band from V 3d states are responsible for the experimentally
      observed visible light absorption. The influence of V dopant concentration on the
      electronic and magnetic properties is also discussed, such as the influence of
      the U value in systems containing oxygen vacancies and spin flip phenomena for
      interstitial V-doping.

PMID- 20683921
TI  - Multilayer substrate-mediated tuning resonance of plasmon and SERS EF of
      nanostructured silver.
AB  - A thin-film of dielectric on a reflecting surface constituting a multilayer
      substrate modulates light intensity due to the interference effect. A
      nanostructure consisting of randomly oriented silver particles of different
      shapes, sizes, and interparticle spacings supports multiple plasmon resonances
      and is observed to have a broad extinction spectrum that spans the entire visible
      region. Combining the two systems by fabricating the nanostructure on the thin
      dielectric film of the multilayer substrate yields a new composite structure
      which is observed to modulate both the extinction spectrum and the SERS EF
      (surface enhanced Raman scattering enhancement factor) of the nanostructure as
      the thickness of the thin-film dielectric is varied. The frequency and intensity
      of the visible extinction spectrum vary dramatically with the dielectric
      thickness and in the intermediate thickness range the spectrum has no visible
      band. The SERS EF determined for the composite structure as a function of the
      thin-film dielectric thickness varies by several orders of magnitude. Strong
      correlation between the magnitude of the SERS EF and the extinction intensity is
      observed over the entire dielectric thickness range indicating that the
      extinction spectrum corresponds to the excitation of the plasmon resonances of
      the nanostructure. A significant finding which has potential applications is that
      the composite structure has synergic effect to boost SERS EF of the nanostructure
      by an order of magnitude or more compared to the same nanostructure on an
      unlayered substrate.

PMID- 20683922
TI  - New anacardic acid-inspired benzamides: histone lysine acetyltransferase
      activators.
AB  - A series of N-(4-cyano-3-trifluoromethyl-phenyl)-2-ethoxy-6-alkyl (and alkenyl)
      benzamides related to the anacardic acid derivative CTPB have been prepared from
      2,6-dihydroxybenzoic acid with a Suzuki coupling and addition of the anion of 4
      cyano-3-trifluoromethylphenylamine to a benzodioxinone as the key steps. In U937
      cells, these analogues, in particular 7 c, 7 d, 7 f and 7 j, induced cell-cycle
      arrest in the G1 phase, caused apoptosis in about 20 % of the cells, and
      increased the acetylation levels of H3. These activities correlate with the
      enzymatic activation of histone lysine acetyltransferases (KATs): CBP and PCAF.

PMID- 20683923
TI  - Prediction of the three-dimensional structure for the rat urotensin II receptor,
      and comparison of the antagonist binding sites and binding selectivity between
      human and rat receptors from atomistic simulations.
AB  - Urotensin-II (U-II) has been shown to be the most potent mammalian
      vasoconstrictor known. Thus, a U-II antagonist might be of therapeutic value in a
      number of cardiovascular disorders. However, interspecies variability of several
      nonpeptidic ligands complicates the interpretation of in vivo studies of such
      antagonists in preclinical animal disease models. ACT058362 is a selective
      antagonist for the human U-II receptor (hUT2R) with a reported K(d) value of
      approximately 4 nM in a molecular binding assay, but it is reported to bind
      weakly to rat UT2R (rUT2R), with a K(d) value of approximately 1 500 nM. In
      contrast, the arylsulphonamide SB706375 is a selective antagonist against both
      hUT2R (K(d)= approximately 9 nM) and rUT2R (K(d)= approximately 21 nM). To
      understand the species selectivity of the UT2R, we investigated the binding site
      of ACT058362 and SB706375 in both hUT2R and rUT2R to explain the dramatically
      lower (approximately 400-fold) affinity of ACT058362 for rUT2R and the similar
      affinity (approximately 10 nM) of SB706375 for both UT2Rs. These studies used
      MembStruk and MSCDock to predict the UT2R structure and the binding site of
      ACT058362 and SB706375. Based on binding energies, we found two binding modes
      each with D130(3.32) as the crucial anchoring point (Ballesteros-Weinstein
      numbering given in superscript). We predict that ACT058362 (an aryl-amine-aryl or
      ANA ligand) binds in the transmembrane (TM) 3456 region, while SB706375 (an aryl
      aryl-amine or AAN ligand) binds in the TM 1237 region. These predicted sites
      explain the known differences in binding of the ANA ligand to rat and human
      receptors, while explaining the similar binding of the AAN compound to rat and
      human receptors. Moreover the predictions explain currently available structure
      activity relationship (SAR) data. To further validate the predicted binding sites
      of these ligands in hUT2R and rUT2R, we propose several mutations that would help
      define the structural origins of differential responses between UT2R of different
      species, potentially indicating novel UT2R antagonists with cross-species high
      affinity.

PMID- 20683924
TI  - Pathological laughter in Gilles de la Tourette syndrome: an unusual phonic tic.
AB  - Patients with Gilles de la Tourette syndrome (GTS) can display socially
      inappropriate behaviors as part of their multiform tic phenomenology.
      Pathological laughter (PL), defined as the presence of episodic and contextually
      inappropriate outbursts of laughter, has been detailed as a symptom of various
      psychiatric and neurological conditions. We present a case series of eight
      subjects diagnosed with GTS who reported PL as part of their tic repertoire. All
      subjects experienced PL as a simple phonic tic, accompanied by characteristic
      premonitory urges and significant impairment in social interactions. In addition,
      all patients presented with multiple tic-related symptoms (mainly self-injurious
      behaviors and echolalia, n = 7; palilalia, n = 6; coprolalia/mental coprolalia, n
      = 5), and six patients had comorbid conditions (in particular obsessive
      compulsive disorder/behaviors, n = 7; attention-deficit hyperactivity disorder, n
      = 4). We suggest that the pathophysiological mechanisms underlying the expression
      of PL as a tic could involve a dissociation between frontostriatal and limbic
      networks.

PMID- 20683925
TI  - Measuring the magnitude of internal motion in a complex hexasaccharide.
AB  - For the development of a scheme for quantitative experimental estimation of
      internal motion in the complex human milk hexasaccharide lacto-N-di-fuco hexose I
      (LNDFH I), we measured a large number of experimental residual dipolar couplings
      in liquid crystal orienting media. We present a total of 40 (13)C--(1)H and (1)H-
      (1)H dipolar coupling values, each representing distinct directions of
      internuclear vectors. The NMR data were interpreted with established methods for
      analysis of rigid subdomains of the oligosaccharide as well as a novel method in
      which dipolar couplings were calculated over an ensemble of conformers from a
      solvent Molecular Dynamics trajectory using multiple linear regression analysis.
      The Lewis(b) epitope region of LNDFH I assumed a single unique conformation with
      internal motion described by fluctuations of 5-10 degrees  in glycosidic dihedral
      angles consistent with previous studies. Greater flexibility was observed for the
      remaining GlcNAc1->3-beta-D-Gal and beta-D-Gal1->4Glc linkages, with the former
      glycosidic linkage existing in a conformational exchange among three states. The
      results were also supported by similar results of calculations carried out with
      conformers obtained from a simple Monte Carlo simulation without explicit
      solvent.

PMID- 20683926
TI  - Practical guidelines addressing ethical issues pertaining to the curation of
      human locus-specific variation databases (LSDBs).
AB  - More than 1,000 Web-based locus-specific variation databases (LSDBs) are listed
      on the Website of the Human Genetic Variation Society (HGVS). These individual
      efforts, which often relate phenotype to genotype, are a valuable source of
      information for clinicians, patients, and their families, as well as for basic
      research. The initiators of the Human Variome Project recently recognized that
      having access to some of the immense resources of unpublished information already
      present in diagnostic laboratories would provide critical data to help manage
      genetic disorders. However, there are significant ethical issues involved in
      sharing these data worldwide. An international working group presents second
      generation guidelines addressing ethical issues relating to the curation of human
      LSDBs that provide information via a Web-based interface. It is intended that
      these should help current and future curators and may also inform the future
      decisions of ethics committees and legislators. These guidelines have been
      reviewed by the Ethics Committee of the Human Genome Organization (HUGO).

PMID- 20683927
TI  - Mutations in GDF5 presenting as semidominant brachydactyly A1.
AB  - Brachydactyly A1 (BDA1) is an autosomal dominant disorder characterized by
      shortness of all middle phalanges of the hands and toes, shortness of the
      proximal phalanges of the first digit, and short stature. Missense mutations in
      the Indian Hedgehog gene (IHH) are known to cause BDA1, and a second locus has
      been mapped to chromosome 5p. In a consanguineous French Canadian kindred with
      BDA1, both IHH and the 5p locus were excluded. Microsatellites flanking GDF5 on
      chromosome 20q were found to cosegregate with the disease. Sequencing of the GDF5
      coding region revealed that a mildly affected individual in the family was
      heterozygous, and that all of the severely affected individuals were homozygous
      for a novel missense c.1195C>T mutation that predicts a p.Arg399Cys substitution
      at a highly conserved amino acid. Functional analysis demonstrated that although
      the p.Arg399Cys mutant is able to stimulate chondrogenesis, it is much less
      effective than wild-type GDF5. This data confirms genetic heterogeneity in BDA1,
      demonstrates that mutations upstream of IHH can result in BDA1, and shows that
      BDA1 can result from semidominant mutations in GDF5.

PMID- 20683929
TI  - Bringing the p53 signature into focus.

PMID- 20683928
TI  - Genetic screening of LCA in Belgium: predominance of CEP290 and identification of
      potential modifier alleles in AHI1 of CEP290-related phenotypes.
AB  - Leber Congenital Amaurosis (LCA), the most severe inherited retinal dystrophy, is
      genetically heterogeneous, with 14 genes accounting for 70% of patients. Here, 91
      LCA probands underwent LCA chip analysis and subsequent sequencing of 6 genes
      (CEP290, CRB1, RPE65, GUCY2D, AIPL1and CRX), revealing mutations in 69% of the
      cohort, with major involvement of CEP290 (30%). In addition, 11 patients with
      early-onset retinal dystrophy (EORD) and 13 patients with Senior-Loken syndrome
      (SLS), LCA-Joubert syndrome (LCA-JS) or cerebello-oculo-renal syndrome (CORS)
      were included. Exhaustive re-inspection of the overall phenotypes in our LCA
      cohort revealed novel insights mainly regarding the CEP290-related phenotype. The
      AHI1 gene was screened as a candidate modifier gene in three patients with the
      same CEP290 genotype but different neurological involvement. Interestingly, a
      heterozygous novel AHI1 mutation, p.Asn811Lys, was found in the most severely
      affected patient. Moreover, AHI1 screening in five other patients with CEP290
      related disease and neurological involvement revealed a second novel missense
      variant, p.His758Pro, in one LCA patient with mild mental retardation and autism.
      These two AHI1 mutations might thus represent neurological modifiers of CEP290
      related disease.

PMID- 20683930
TI  - The potent bile acid sequestrant colesevelam is not effective in cholestatic
      pruritus: results of a double-blind, randomized, placebo-controlled trial.
AB  - Colesevelam is an anion-exchange resin with a 7-fold higher bile acid-binding
      capacity and fewer side effects than cholestyramine, the current first-line
      treatment option for cholestatic pruritus. The aim of this trial was to compare
      the effects of colesevelam and a placebo in patients with cholestatic pruritus.
      In a randomized, double-blind, investigator-initiated, multicenter trial,
      patients with cholestatic pruritus, both treatment-naive and previously treated,
      received 1875 mg of colesevelam or an identical placebo twice daily for 3 weeks.
      The effect on pruritus was assessed with daily visual analogue scales, quality-of
      life scores, and evaluations of cutaneous scratch lesions. The predefined primary
      endpoint was the proportion of patients with at least a 40% reduction in pruritus
      visual analogue scale scores. Thirty-eight patients were included, and 35 were
      evaluable: 17 took colesevelam, 18 took the placebo, 22 were female, 8 were
      treatment-naive, 14 had primary biliary cirrhosis, and 14 had primary sclerosing
      cholangitis. The mean serum bile acid levels were comparable between the groups
      before treatment (P = 0.74), but they were significantly different after
      treatment (P = 0.01) in favor of patients treated with colesevelam. Thirty-six
      percent of patients in the colesevelam group reached the primary endpoint versus
      35% in the placebo group (P = 1.0). There were no significant differences between
      the groups with respect to pruritus scores, quality-of-life scores, and severity
      of cutaneous scratch lesions. Mild side effects occurred in one colesevelam
      treated patient and four placebo-treated patients. CONCLUSION: Although
      colesevelam significantly decreased serum bile acid levels, this trial was unable
      to demonstrate that it was more effective than a placebo in alleviating the
      severity of pruritus of cholestasis.

PMID- 20683931
TI  - A multifaceted imbalance of T cells with regulatory function characterizes type 1
      autoimmune hepatitis.
AB  - Immunotolerance is maintained by regulatory T cells (Tregs), including
      CD4(+)CD25(hi), CD8(+)CD28(-), gammadelta, and CD3(+)CD56(+) [natural killer T
      (NKT)] cells. CD4(+)CD25(hi) cells are impaired in children with autoimmune
      hepatitis (AIH). Little is known about Tregs in adults with AIH. The aim of this
      study was to investigate the frequency and function of Treg subsets in adult
      patients with AIH during periods of active disease and remission. Forty-seven AIH
      patients (16 with active disease and 31 in remission) and 28 healthy controls
      were studied. Flow cytometry was used to evaluate surface markers and function
      related intracellular molecules in gammadelta, CD8(+)CD28(-), NKT, and
      CD4(+)CD25(hi) cells. CD4(+)CD25(hi) T cell function was determined by the
      ability to suppress proliferation and interferon gamma (IFN-gamma) production by
      CD4(+)CD25(-) target cells. Liver forkhead box P3-positive (FOXP3(+)) cells were
      sought by immunohistochemistry. In AIH patients, particularly during active
      disease, CD4(+)CD25(hi) T cells were fewer, expressed lower levels of FOXP3, and
      were less effective at inhibiting target cell proliferation versus healthy
      controls. Moreover, although the numbers of CD8(+)CD28(-) T cells were similar in
      AIH patients and healthy controls, NKT cells were numerically reduced, especially
      during active disease, and produced lower quantities of the immunoregulatory
      cytokine interleukin-4 versus controls. In contrast, gammadelta T cells in AIH
      patients were more numerous versus healthy controls and had an inverted
      Vdelta1/Vdelta2 ratio and higher IFN-gamma and granzyme B production; the latter
      was correlated to biochemical indices of liver damage. There were few FOXP3(+)
      cells within the portal tract inflammatory infiltrate. CONCLUSION: Our data show
      that the defect in immunoregulation in adult AIH is complex, and gammadelta T
      cells are likely to be effectors of liver damage.

PMID- 20683932
TI  - Long-term entecavir therapy results in the reversal of fibrosis/cirrhosis and
      continued histological improvement in patients with chronic hepatitis B.
AB  - One year of treatment with entecavir (0.5 mg daily) in nucleoside-naive patients
      with hepatitis B e antigen (HBeAg)-positive or HBeAg-negative chronic hepatitis B
      (CHB) resulted in significantly improved liver histology and virological and
      biochemical endpoints in comparison with lamivudine. Patients who received at
      least 3 years of cumulative entecavir therapy in phase 3 studies and a long-term
      rollover study and underwent long-term liver biopsy were evaluated for
      improvements in histological appearance. Sixty-nine patients [50 HBeAg-positive
      and 19 HBeAg-negative] receiving entecavir therapy underwent long-term liver
      biopsy (median time of biopsy = 6 years, range = 3-7 years). Histological
      improvement was analyzed for 57 patients who had adequate baseline biopsy
      samples, baseline Knodell necroinflammatory scores > or =2, and adequate long
      term biopsy samples. At the time of long-term biopsy, all patients in the cohort
      had a hepatitis B virus DNA level <300 copies/mL, and 86% had a normalized
      alanine aminotransferase level. Histological improvement (> or =2-point decrease
      in the Knodell necroinflammatory score and no worsening of the Knodell fibrosis
      score) was observed in 96% of patients, and a > or =1-point improvement in the
      Ishak fibrosis score was found in 88% of patients, including all 10 patients with
      advanced fibrosis or cirrhosis at the phase 3 baseline. CONCLUSION: The majority
      of nucleoside-naive patients with CHB who were treated with entecavir in this
      long-term cohort achieved substantial histological improvement and regression of
      fibrosis or cirrhosis.

PMID- 20683933
TI  - Possible role of adipocytokines in the development of nonalcoholic
      steatohepatitis-related hepatocellular carcinoma.

PMID- 20683934
TI  - Role of fibroblast growth factor signaling during proepicardium formation in the
      chick embryo.
AB  - The proepicardium forms at the venous pole of the embryonic heart and gives rise
      to several cell types of the mature heart. We investigated the role of fibroblast
      growth factors (FGFs) during proepicardium formation in the chick embryo. Several
      FGF ligands (Fgf2, Fgf10, and Fgf12) and receptors (Fgfr1, Fgfr2, and Fgfr4) are
      expressed in the proepicardium. Experimental modulation of FGF signaling in
      explant cultures affected cell proliferation and survival. In contrast,
      expression of Tbx18, Wt1, or Tbx5 were unaffected by FGF inhibition. In agreement
      with the explant data, villous outgrowth of the proepicardium was strongly
      impaired by FGF inhibition in vivo, however Tbx18 expression was maintained.
      These data suggest that during proepicardium formation, FGF ligands act as
      autocrine or paracrine growth factors to prevent apoptosis, maintain
      proliferation, and to promote villous outgrowth of the proepicardium. However,
      FGF is not involved in the induction or maintenance of proepicardium-specific
      marker gene expression.

PMID- 20683936
TI  - Isolated laryngeal myokymia: diagnosis and treatment.
AB  - Myokymia is an uncommon neuromuscular disorder that rarely affects the human
      larynx. No previous reports of isolated laryngeal myokymia are present in the
      literature, and as such, established treatment protocols are lacking. We report
      the first case of isolated laryngeal myokymia in a 48-year-old woman with no
      other neurological findings, and our successful results in initial treatment and
      maintenance therapy with focal intralaryngeal injections of botulinum toxin A.

PMID- 20683935
TI  - CX3CL1-CX3CR1 interaction prevents carbon tetrachloride-induced liver
      inflammation and fibrosis in mice.
AB  - Chronic liver disease is associated with hepatocyte injury, inflammation, and
      fibrosis. Chemokines and chemokine receptors are key factors for the migration of
      inflammatory cells such as macrophages and noninflammatory cells such as hepatic
      stellate cells (HSCs). The expression of CX3CR1 and its ligand, CX3CL1, is up
      regulated in chronic liver diseases such as chronic hepatitis C. However, the
      precise role of CX3CR1 in the liver is still unclear. Here we investigated the
      role of the CX3CL1-CX3CR1 interaction in a carbon tetrachloride (CCl(4))-induced
      liver inflammation and fibrosis model. CX3CR1 was dominantly expressed in Kupffer
      cells in the liver. In contrast, the main source of CX3CL1 was HSCs. Mice
      deficient in CX3CR1 showed significant increases in inflammatory cell recruitment
      and cytokine production [including tumor necrosis factor alpha (TNF-alpha);
      monocyte chemoattractant protein 1; macrophage inflammatory protein 1beta; and
      regulated upon activation, normal T cell expressed, and secreted (RANTES)] after
      CCl(4) treatment versus wild-type (WT) mice. This suggested that CX3CR1 signaling
      prevented liver inflammation. Kupffer cells in CX3CR1-deficient mice after CCl(4)
      treatment showed increased expression of TNF-alpha and transforming growth factor
      beta and reduced expression of the anti-inflammatory markers interleukin-10 (IL
      10) and arginase-1. Coculture experiments showed that HSCs experienced
      significantly greater activation by Kupffer cells from CCl(4)-treated CX3CR1
      deficient mice versus WT mice. Indeed, augmented fibrosis was observed in CX3CR1
      deficient mice versus WT mice after CCl(4) treatment. Finally, CX3CL1 treatment
      induced the expression of IL-10 and arginase-1 in WT cultured Kupffer cells
      through CX3CR1, which in turn suppressed HSC activation. CONCLUSION: The CX3CL1
      CX3CR1 interaction inhibits inflammatory properties in Kupffer cells/macrophages
      and results in decreased liver inflammation and fibrosis.

PMID- 20683937
TI  - Mapping residue-specific contacts of polymyxin B with lipopolysaccharide by
      saturation transfer difference NMR: insights into outer-membrane disruption and
      endotoxin neutralization.
AB  - High-resolution interactions studies of molecules with lipopolysaccharide (LPS)
      or endotoxin are important for health, diseases and environment. LPS is the major
      constituent of the outer layer of the outer membrane of the gram-negative
      bacteria. LPS provides an efficient barrier against permeation of variety of
      compounds including antibacterial agents and antimicrobial peptides. In the
      intensive care units, LPS is known for the fatal septic shock syndromes. Because
      of LPS toxicity, high affinity LPS sensors are sought-after for the assessment of
      the quality of water and pharmaceutical products. Therefore, elucidation of
      binding epitopes of LPS interacting molecules would be vital for the development
      of antimicrobial, antiendotoxic molecules. Polymyxin B (PMB), an antibacterial
      cyclic lipo-peptide, is well known for its LPS sequestering and neutralizing
      activities. Here, we have used saturation transfer difference (STD) NMR methods
      for characterizing interactions of PMB with LPS from E. coli 0111:B4 and P.
      aeruginosa. The dissociation constants of the LPS-PMB complexes were obtained
      from concentration dependent STD studies. Further a detailed epitope mapping of
      PMB has been carried out in E. coli 0111:B4 LPS micelles. Experiments including
      one-dimensional 1H STD, two-dimensional 1H-1H STD-TOCSY and naturalabundance 13C
      1H STD-HSQC, are performed to determine the site(s) of interactions of PMB with
      endotoxin at atomic resolution. Our studies reveal that the hydrophobic
      sidechains of PMB including a part of the N-terminus lipidic tail demonstrate
      close contacts with LPS. In contrast, cyclic backbone structure of PMB has the
      lowest STD effects suggesting a rather loose association with endotoxin.

PMID- 20683938
TI  - Use of a low profile ultrasound transducer for coronary sinus cannulation: a
      pilot study.
AB  - BACKGROUND: Cardiac resynchronization therapy with biventricular pacing has been
      shown to be beneficial in improving heart failure in patients with prolonged QRS
      duration (>=120 ms) and low ejection fraction (<=35%). Unsuccessful cannulation
      of the coronary sinus (CS) has been reported in up to 10% of cases. The
      feasibility of the transthoracic continuous cardiac imaging for coronary sinus
      cannulation has not been previously demonstrated. METHODS AND RESULTS: We
      developed a 2.5-MHz hemi-spherical continuous cardiac imaging transducer
      (CONTISON), mounted in an external housing, to permit steering in 360 degrees .
      The transducer was attached to the chest wall using an adhesive ring. The CS was
      easily imaged by echocardiography by placing the transducer just medial to the
      apex and tilting it dorsally. The feasibility study was done in 11 patients. CS
      ostium and body were imaged in all patients. Cannulation was successfully
      achieved in nine patients with a mean cannulation time of 1 minute 16 seconds. In
      two patients, poor image quality precluded adequate visualization of CS.
      Fluoroscopy was not used for cannulation. CONCLUSION: We demonstrated the
      feasibility of using the CONTISON echography transducer for the guidance CS
      cannulation. This technique could expedite CS cannulation and reduce radiation
      exposure. Further studies comparing ultrasound versus fluoroscopy for CS
      cannulation appear warranted.

PMID- 20683939
TI  - Efficacy, effectiveness, and comparative effectiveness in liver disease.

PMID- 20683940
TI  - New insights into the role of iron in the development of nonalcoholic fatty liver
      disease.

PMID- 20683941
TI  - Involvement of PA28gamma in the propagation of hepatitis C virus.
AB  - We have reported previously that the proteasome activator PA28gamma participates
      not only in degradation of hepatitis C virus (HCV) core protein in the nucleus
      but also in the pathogenesis in transgenic mice expressing HCV core protein.
      However, the biological significance of PA28gamma in the propagation of HCV has
      not been clarified. PA28gamma is an activator of proteasome responsible for
      ubiquitin-independent degradation of substrates in the nucleus. In the present
      study, knockdown of PA28gamma in cells preinfection or postinfection with the JFH
      1 strain of HCV impaired viral particle production but exhibited no effect on
      viral RNA replication. The particle production of HCV in PA28gamma knockdown
      cells was restored by the expression of an small interfering RNA (siRNA)
      resistant PA28gamma. Although viral proteins were detected in the cytoplasm of
      cells infected with HCV, suppression of PA28gamma expression induced accumulation
      of HCV core protein in the nucleus. HCV core protein was also degraded in the
      cytoplasm after ubiquitination by an E3 ubiquitin ligase, E6AP. Knockdown of
      PA28gamma enhanced ubiquitination of core protein and impaired virus production,
      whereas that of E6AP reduced ubiquitination of core protein and enhanced virus
      production. Furthermore, virus production in the PA28gamma knockdown cells was
      restored through knockdown of E6AP or expression of the siRNA-resistant wild-type
      but not mutant PA28gamma incapable of activating proteasome activity. CONCLUSION:
      Our results suggest that PA28gamma participates not only in the pathogenesis but
      also in the propagation of HCV by regulating the degradation of the core protein
      in both a ubiquitin-dependent and ubiquitin-independent manner.

PMID- 20683942
TI  - Evaluation of depression as a risk factor for treatment failure in chronic
      hepatitis C.
AB  - The Major Depression Inventory (MDI) was used to estimate the value of routine
      medical interviews in diagnosing major depression among patients receiving
      peginterferon alfa-2a and ribavirin therapy for chronic hepatitis C virus (HCV)
      infection (n = 325). According to criteria from the MDI and Diagnostic and
      Statistical Manual of Mental Disorders (DSM-IV), 19 patients (6%) had major
      depression at baseline. An additional 114 (37%) developed depression while on HCV
      combination therapy, with baseline MDI score and female sex independently
      predicting the emergence of major depression during treatment in a multivariate
      analysis. Only 36 (32%) of the 114 patients developing major depression according
      to MDI/DSM-IV criteria were correctly diagnosed during routine medical
      interviews. The emergence of major depression frequently led to premature
      discontinuation of peginterferon/ribavirin therapy, and an on-treatment MDI score
      increment exceeding 30 points (i.e., a validated marker of idiopathic DSM-IV
      major depression) was correlated with impaired outcome of HCV therapy (P = 0.02).
      This difference was even more pronounced among patients with an on-treatment
      increase in MDI score greater than 35 points (P = 0.003). CONCLUSION: We conclude
      that (1) depressive symptoms among patients undergoing HCV therapy are commonly
      overlooked by routine clinical interviews, (2) the emergence of depression
      compromises the outcome of HCV therapy, and (3) the MDI scale may be useful in
      identifying patients at risk for treatment-induced depression.

PMID- 20683943
TI  - The impact of hepatitis C virus infection on work absence, productivity, and
      healthcare benefit costs.
AB  - Chronic hepatitis C virus (HCV) infection is generally considered an asymptomatic
      disease. However, studies have shown that HCV has a substantial negative impact
      on patients' quality of life and functioning. This study was designed to compare
      absenteeism, productivity, and health cost between employees with and without HCV
      infection in the United States. Employee records from multiple large employers in
      the United States were obtained from the Human Capital Management Services
      Research Reference Database and were assessed for demographics, salary,
      healthcare use, work loss, and workers' compensation. HCV-infected subjects were
      identified by International Classification of Diseases 9th revision Clinical
      Modification codes. Controls were randomly selected from employees not diagnosed
      with HCV. T-tests and chi-square tests were used to determine if there were
      differences in demographic characteristics. Regression modeling compared days
      absent (among benefit-eligible employees) and productivity (among employees with
      data on task-oriented activities), while controlling for the impact of
      confounding factors. A total of 339,456 subjects were evaluated. Employees with
      HCV (n = 1664) had significantly more lost work days per employee than the
      control cohort (n = 337,792), including sick leave, short-term disability, and
      long-term disability. HCV-infected workers had 4.15 more days of absence per
      employee than the control cohort. Productivity was measured by units of work
      processed per hour; employees with HCV processed 7.5% fewer units per hour than
      employees without HCV (P > 0.05). All healthcare benefit costs among HCV
      employees were significantly higher than the same costs among employees without
      HCV. Overall, the total incremental difference was $8352 per year. CONCLUSION:
      This real world study provides evidence that there is a substantial indirect
      burden of illness and describes a relationship between HCV infection,
      productivity, increased absenteeism, and higher healthcare benefit costs.

PMID- 20683944
TI  - Transcriptome sequencing, microarray, and proteomic analyses reveal cellular and
      metabolic impact of hepatitis C virus infection in vitro.
AB  - Hepatitis C virus (HCV) is a major cause of liver disease but the full impact of
      HCV infection on the hepatocyte is poorly understood. RNA sequencing (RNA-Seq) is
      a novel method to analyze the full transcriptional activity of a cell or tissue,
      thus allowing new insight into the impact of HCV infection. We conducted the
      first full-genome RNA-Seq analysis in a host cell to analyze infected and
      noninfected cells, and compared this to microarray and proteomic analyses. The
      combined power of the triple approach revealed that HCV infection affects a
      number of previously unreported canonical pathways and biological functions,
      including pregnane X receptor/retinoic acid receptor activation as a potential
      host antiviral response, and integrin-linked kinase signaling as an entry factor.
      This approach also identified several mechanisms implicated in HCV pathogenesis,
      including an increase in reactive oxygen species. HCV infection had a broad
      effect on cellular metabolism, leading to increases in cellular cholesterol and
      free fatty acid levels, associated with a profound and specific decrease in
      cellular glucose levels. CONCLUSION: RNA-Seq technology, especially when combined
      with established methods, demonstrated that HCV infection has potentially wide
      ranging effects on cellular gene and protein expression. This in vitro study
      indicates a substantial metabolic impact of HCV infection and highlights new
      mechanisms of virus-host interaction which may be highly relevant to pathogenesis
      in vivo.

PMID- 20683945
TI  - Early on-treatment prediction of response to peginterferon alfa-2a for HBeAg
      negative chronic hepatitis B using HBsAg and HBV DNA levels.
AB  - Peginterferon alfa-2a results in a sustained response (SR) in a minority of
      patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB).
      This study investigated the role of early on-treatment serum hepatitis B surface
      antigen (HBsAg) levels in the prediction of SR in HBeAg-negative patients
      receiving peginterferon alfa-2a. HBsAg (Architect from Abbott) was quantified at
      the baseline and during treatment (weeks 4, 8, 12, 24, 36, and 48) and follow-up
      (weeks 60 and 72) in the sera from 107 patients who participated in an
      international multicenter trial (peginterferon alfa-2a, n = 53, versus
      peginterferon alfa-2a and ribavirin, n = 54). Overall, 24 patients (22%) achieved
      SR [serum hepatitis B virus (HBV) DNA level < 10,000 copies/mL and normal alanine
      aminotransferase levels at week 72]. Baseline characteristics were comparable
      between sustained responders and nonresponders. From week 8 onward, serum HBsAg
      levels markedly decreased in sustained responders, whereas only a modest decline
      was observed in nonresponders. However, HBsAg declines alone were of limited
      value in the prediction of SR [area under the receiver operating characteristic
      curve (AUC) at weeks 4, 8, and 12 = 0.59, 0.56, and 0.69, respectively].
      Combining the declines in HBsAg and HBV DNA allowed the best prediction of SR
      (AUC at week 12 = 0.74). None of the 20 patients (20% of the study population) in
      whom a decrease in serum HBsAg levels was absent and whose HBV DNA levels
      declined less than 2 log copies/mL exhibited an SR (negative predictive value =
      100%). CONCLUSION: At week 12 of peginterferon alfa-2a treatment for HBeAg
      negative CHB, a solid stopping rule was established with a combination of
      declines in serum HBV DNA and HBsAg levels from the baseline. Quantitative serum
      HBsAg in combination with HBV DNA enables on-treatment adjustments of
      peginterferon therapy for HBeAg-negative CHB.

PMID- 20683946
TI  - Hepatic iron loading in mice increases cholesterol biosynthesis.
AB  - Iron and cholesterol are both essential metabolites in mammalian systems, and too
      much or too little of either can have serious clinical consequences. In addition,
      both have been associated with steatosis and its progression, contributing, inter
      alia, to an increase in hepatic oxidative stress. The interaction between iron
      and cholesterol is unclear, with no consistent evidence emerging with respect to
      changes in plasma cholesterol on the basis of iron status. We sought to clarify
      the role of iron in lipid metabolism by studying the effects of iron status on
      hepatic cholesterol synthesis in mice with differing iron status. Transcripts of
      seven enzymes in the cholesterol biosynthesis pathway were significantly up
      regulated with increasing hepatic iron (R(2) between 0.602 and 0.164), including
      those of the rate-limiting enzyme, 3-hydroxy-3-methylglutarate-coenzyme A
      reductase (Hmgcr; R(2) = 0.362, P < 0.002). Hepatic cholesterol content
      correlated positively with hepatic iron (R(2) = 0.255, P < 0.007). There was no
      significant relationship between plasma cholesterol and either hepatic
      cholesterol or iron (R(2) = 0.101 and 0.014, respectively). Hepatic iron did not
      correlate with a number of known regulators of cholesterol synthesis, including
      sterol-regulatory element binding factor 2 (Srebf2; R(2) = 0.015), suggesting
      that the increases seen in the cholesterol biosynthesis pathway are independent
      of Srebf2. Transcripts of genes involved in bile acid synthesis, transport, or
      regulation did not increase with increasing hepatic iron. CONCLUSION: This study
      suggests that hepatic iron loading increases liver cholesterol synthesis and
      provides a new and potentially important additional mechanism by which iron could
      contribute to the development of fatty liver disease or lipotoxicity.

PMID- 20683947
TI  - High-dose ursodeoxycholic acid therapy for nonalcoholic steatohepatitis: a double
      blind, randomized, placebo-controlled trial.
AB  - In uncontrolled clinical studies, ursodeoxycholic acid (UDCA) had a beneficial
      effect on nonalcoholic steatohepatitis (NASH). However, a large controlled trial
      using UDCA (13-15 mg/kg/day) was unable to confirm these results. Accordingly, a
      randomized, placebo-controlled study was initiated with a high dose of UDCA (23
      28 mg/kg/day). The allocation of patients and the evaluation of liver histology
      were performed according to a modified Brunt score and the nonalcoholic fatty
      liver disease activity score (NAS). With the modified Brunt score, 185 patients
      with histologically proven NASH were randomized [intention to treat (ITT)], and
      147 were treated per protocol (PP). With the NAS, 137 patients were confirmed to
      have NASH, 48 had borderline NASH, and 1 did not have NASH. The treatment time
      was 18 months. At entry, the treatment groups were comparable. A second biopsy
      sample was obtained from 139 of 185 patients (NAS: 107/137). The primary
      criterion for evaluation was a change in the liver histology; the secondary
      criteria were single histological variables and liver biochemistry. Significant
      differences in the overall histology could not be detected between the two
      treatment groups with the modified Brunt score (P = 0.881) or NAS (P = 0.355).
      Only lobular inflammation improved significantly (P for the modified Brunt score
      = 0.011, P for NAS = 0.005). In subgroup analyses, significant improvements in
      lobular inflammation were also observed in males, younger patients up to 50 years
      of age, slightly overweight patients, and patients with hypertension and an
      increased histology score. The fibrosis score did not change (P for ITT = 0.133,
      P for PP = 0.140). With the exception of gamma-glutamyl transferase, UDCA did not
      improve laboratory data. CONCLUSION: High-dose UDCA failed to improve the overall
      histology in patients with NASH in comparison with placebo.

PMID- 20683948
TI  - c-Jun mediates hepatitis C virus hepatocarcinogenesis through signal transducer
      and activator of transcription 3 and nitric oxide-dependent impairment of
      oxidative DNA repair.
AB  - Hepatocellular carcinoma (HCC) occurs in a significant number of patients with
      hepatitis C virus (HCV) infection. HCV causes double-strand DNA breaks and
      enhances the mutation frequency of proto-oncogenes and tumor suppressors.
      However, the underlying mechanisms for these oncogenic events are still elusive.
      Here, we studied the role of c-Jun, signal transducer and activator of
      transcription 3 (STAT3), and nitric oxide (NO) in spontaneous and
      diethylnitrosamine (DEN)-initiated and/or phenobarbital (Pb)-promoted HCC
      development using HCV core transgenic (Tg) mice. The viral core protein induces
      hepatocarcinogenesis induction as a tumor initiator under promotion by Pb
      treatment alone. Conditional knockout of c-jun and stat3 in hepatocytes achieves
      a nearly complete, additive effect on prevention of core-induced spontaneous HCC
      or core-enhanced HCC incidence caused by DEN/Pb. Core protein induces hepatocyte
      proliferation and the expression of inflammatory cytokines (interleukin-6, tumor
      necrosis factor-alpha, interleukin-1) and inducible NO synthase (iNOS); the
      former is dependent on c-Jun and STAT3, and the latter on c-Jun. Oxidative DNA
      damage repair activity is impaired by the HCV core protein due to reduced DNA
      glycosylase activity for the excision of 8-oxo-2'-deoxyguanosine. This impairment
      is abrogated by iNOS inhibition or c-Jun deficiency, but aggravated by the NO
      donor or iNOS-inducing cytokines. The core protein also suppresses apoptosis
      mediated by Fas ligand because of c-Jun-dependent Fas down-regulation.
      CONCLUSION: These results indicate that the HCV core protein potentiates
      chemically induced HCC through c-Jun and STAT3 activation, which in turn,
      enhances cell proliferation, suppresses apoptosis, and impairs oxidative DNA
      damage repair, leading to hepatocellular transformation.

PMID- 20683949
TI  - Thiazolidinediones inhibit hepatocarcinogenesis in hepatitis B virus-transgenic
      mice by peroxisome proliferator-activated receptor gamma-independent regulation
      of nucleophosmin.
AB  - Antidiabetic thiazolidinediones (TZD) have in vitro antiproliferative effect in
      epithelial cancers, including hepatocellular carcinoma (HCC). The effective
      anticancer properties and the underlying molecular mechanisms of these drugs in
      vivo remain unclear. In addition, the primary biological target of TZD, the
      ligand-dependent transcription factor peroxisome proliferator-activated receptor
      gamma (PPARgamma), is up-regulated in HCC and seems to provide tumor-promoting
      responses. The aim of our study was to evaluate whether chronic administration of
      TZD may affect hepatic carcinogenesis in vivo in relation to PPARgamma expression
      and activity. The effect of TZD oral administration for 26 weeks was tested on
      tumor formation in PPARgamma-expressing and PPARgamma-deficient mouse models of
      hepatic carcinogenesis. Proteomic analysis was performed in freshly isolated
      hepatocytes by differential in gel electrophoresis and mass spectrometry
      analysis. Identified TZD targets were confirmed in cultured PPARgamma-deficient
      hepatocytes. TZD administration in hepatitis B virus (HBV)-transgenic mice
      (TgN[Alb1HBV]44Bri) reduced tumor incidence in the liver, inhibiting hepatocyte
      proliferation and increasing apoptosis. PPARgamma deletion in hepatocytes of HBV
      transgenic mice (Tg[HBV]CreKOgamma) did not modify hepatic carcinogenesis but
      increased the TZD antitumorigenic effect. Proteomic analysis identified
      nucleophosmin (NPM) as a TZD target in PPARgamma-deficient hepatocytes. TZD
      inhibited NPM expression at protein and messenger RNA levels and decreased NPM
      promoter activity. TZD inhibition of NPM was associated with the induction of p53
      phosphorylation and p21 expression. CONCLUSION: These findings suggest that
      chronic administration of TZD has anticancer activity in the liver via inhibition
      of NPM expression and indicate that these drugs might be useful for HCC
      chemoprevention and treatment.

PMID- 20683950
TI  - Synergistic role of Sprouty2 inactivation and c-Met up-regulation in mouse and
      human hepatocarcinogenesis.
AB  - Sprouty2 (Spry2), a negative feedback regulator of the Ras/mitogen-activated
      protein kinase (MAPK) pathway, is frequently down-regulated in human
      hepatocellular carcinoma (HCC). We tested the hypothesis that loss of Spry2
      cooperates with unconstrained activation of the c-Met protooncogene to induce
      hepatocarcinogenesis via in vitro and in vivo approaches. We found coordinated
      down-regulation of Spry2 protein expression and activation of c-Met as well as
      its downstream effectors extracellular signal-regulated kinase (ERK) and v-akt
      murine thymoma viral oncogene homolog (AKT) in a subset of human HCC samples with
      poor outcome. Mechanistic studies revealed that Spry2 function is disrupted in
      human HCC via multiple mechanisms at both transcriptional and post
      transcriptional level, including promoter hypermethylation, loss of
      heterozygosity, and proteosomal degradation by neural precursor cell expressed,
      developmentally down-regulated 4 (NEDD4). In HCC cell lines, Spry2 overexpression
      inhibits c-Met-induced cell proliferation as well as ERK and AKT activation,
      whereas loss of Spry2 potentiates c-Met signaling. Most importantly, we show that
      blocking Spry2 activity via a dominant negative form of Spry2 cooperates with c
      Met to promote hepatocarcinogenesis in the mouse liver by sustaining
      proliferation and angiogenesis. The tumors exhibited high levels of activated ERK
      and AKT, recapitulating the subgroup of human HCC with a clinically aggressive
      phenotype. CONCLUSION: The occurrence of frequent genetic, epigenetic, and
      biochemical events leading to Spry2 inactivation provides solid evidence that
      Spry2 functions as a tumor suppressor gene in liver cancer. Coordinated
      deregulation of Spry2 and c-Met signaling may be a pivotal oncogenic mechanism
      responsible for unrestrained activation of ERK and AKT pathways in human
      hepatocarcinogenesis.

PMID- 20683951
TI  - Effect of aging on risk for hepatocellular carcinoma in chronic hepatitis C virus
      infection.
AB  - An increase in the aging population is an impending problem. A large cohort study
      was carried out to determine the influence of aging and other factors on
      hepatocarcinogenesis in patients treated with interferon. Biopsy-proven 2547
      chronic hepatitis C patients registered at our referral center since 1992 were
      included. Of these, 2166 were treated with interferon-based therapy. Incidences
      of hepatocellular carcinoma (HCC) associated with interferon were analyzed by
      Kaplan-Meier and person-years methods for an average follow-up of 7.5 years.
      Factors associated with HCC risk were determined by Cox proportional hazard
      analysis. HCC developed in 177 interferon-treated patients. The risk for HCC
      depended on age at primary biopsy and increased more than 15-fold after 65 years
      of age. Even when stratified by stage of fibrosis, the cumulative and annual
      incidences of HCC were significantly higher in older patients than in younger
      patients (P < 0.001) at the same stage of fibrosis, except for cirrhosis.
      Progression of fibrosis over time was significantly accelerated in older
      patients. The impact of viral eradication on HCC prevention was less significant
      in older patients than in younger patients. Multivariate analysis confirmed that
      age, gender, liver fibrosis, liver steatosis, total cholesterol level, fasting
      blood sugar level, baseline and postinterferon alpha-fetoprotein level, and
      virological response to interferon were independent risk factors associated with
      HCC. Aging was the strongest risk factor for a nonvirological response to
      interferon-based antiviral therapy. CONCLUSION: Elderly patients are at a higher
      risk for HCC. Hepatitis C viral eradication had a smaller effect on
      hepatocarcinogenesis in older patients. Patients should therefore be identified
      at an earlier age and treatment should be initiated.

PMID- 20683952
TI  - Octamer 4 (Oct4) mediates chemotherapeutic drug resistance in liver cancer cells
      through a potential Oct4-AKT-ATP-binding cassette G2 pathway.
AB  - Chemoresistance presents a major obstacle to the efficacy of chemotherapeutic
      treatment of cancers. Using chemotherapeutic drugs to select drug-resistant
      cancer cells in hepatocellular carcinoma (HCC) and several other cancer cell
      lines, we demonstrate that chemoresistant cells displayed cancer stem cell
      features, such as increased self-renewal ability, cell motility, multiple drug
      resistance, and tumorigenicity. Octamer 4 (Oct4) messenger RNA (mRNA) levels were
      dramatically increased in chemoresistant cancer cells due to DNA demethylation
      regulation of Oct4. By functional study, Oct4 overexpression enhanced whereas
      Oct4 knockdown reduced liver cancer cell resistance to chemotherapeutic drugs in
      vitro and in xenograft tumors. It is known that the Oct4-TCL1-AKT pathway acts on
      embryonic stem cells and cancer stem cells in cell proliferation through
      inhibition of apoptosis. We further demonstrate that Oct4 overexpression induced
      activation of TCL1, AKT, and ABCG2 to mediate chemoresistance, which can be
      overcome by addition of the PI3K/AKT inhibitor; therefore, a direct pathway of
      Oct4-TCL1-AKT-ABCG2 or a combination of Oct4-TCL1-AKT with the AKT-ABCG2 pathway
      could be a potential new mechanism involved in liver cancer cell chemoresistance.
      Moreover, the clinical significance of the Oct4-AKT-ABCG2 pathway can be
      demonstrated in HCC patients, with a strong correlation of expression patterns in
      human HCC tumors. The role of the Oct4-AKT-ABCG2 axis in cancer cell
      chemoresistant machinery suggests that AKT pathway inhibition (PI3K inhibitors)
      not only inhibits cancer cell proliferation, but may also enhance
      chemosensitivity by target potential chemoresistant cells. CONCLUSION: Oct4, a
      transcriptional factor of pluripotent cells, can mediate chemoresistance through
      a potential Oct4-AKT-ABCG2 pathway.

PMID- 20683953
TI  - Molecular characterization of the vascular features of focal nodular hyperplasia
      and hepatocellular adenoma: a role for angiopoietin-1.
AB  - Focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA) are two hepatic
      nodular lesions of different etiologies. FNH, a polyclonal lesion, is assumed to
      be a regenerative reaction following a vascular injury, whereas HCA is a
      monoclonal, benign neoplastic lesion. In addition to features that are
      predominantly found in either FNH or HCA (e.g., dystrophic vessels in FNH and
      single arteries in HCA), FNH and HCA share morphological vascular abnormalities
      such as dilated sinusoids. We hypothesized that these anomalous vascular features
      are associated with altered expression of growth factors involved in vascular
      remodeling. This was based on reports of morphologically abnormal hepatic
      vasculature and nodular lesions in transgenic models of hepatocytic
      overexpression of angiopoietin-1 (Ang-1), a member of the angiopoietin family,
      which is crucially involved in vascular morphogenesis and homeostasis. We
      investigated gene and protein expression of members of the angiopoietin system
      and vascular endothelial growth factor A (VEGF-A) and its receptors in 9 FNH
      samples, 13 HCA samples, and 9 histologically normal livers. In comparison with
      normal samples, a significant increase in Ang-1 was found in FNH (P < 0.01) and
      HCA (P < 0.05), whereas no significant changes in Ang-2, receptor tyrosine kinase
      with immunoglobulin-like and EGF-like domains 2, VEGF-A, or vascular endothelial
      growth factor receptor 2 (VEGFR-2) were observed. CONCLUSION: Because of the
      different etiological contexts of a preceding vascular injury in FNH and a
      neoplastic growth in HCA, Ang-1 might exert different effects on the vasculature
      in these lesions. In FNH, it could predominantly stimulate recruitment of
      myofibroblasts and result in dystrophic vessels, whereas in HCA, it may drive
      vascular remodeling that produces enlarged vessels and arterial sprouting that
      generates single arteries.

PMID- 20683955
TI  - The specificity of fatigue in primary biliary cirrhosis: evaluation of a large
      clinic practice.
AB  - Quality of life is an important concern for patients with chronic liver disease.
      We sought to describe the frequency, severity, and associations of fatigue, in
      patients with primary biliary cirrhosis (PBC). We performed association testing
      between PBC-40 multidomain disease-specific quality of life responses and
      clinical findings. Three hundred twenty-seven patients from a single clinic with
      PBC (94% female, 92% AMA-positive) were evaluated. The average age was 57 years
      and average disease duration 7.2 years. Verbally reported fatigue was noted in
      48% but present in the overwhelming majority on PBC-40 completion, with 44%
      having moderate or severe symptoms. Of those not complaining of fatigue
      clinically, 25% documented moderate or severe fatigue by questionnaire. Age had
      an inverse relationship with fatigue (P < 0.01), whereas body mass index (BMI)
      was positively associated (P < 0.01), as was the presence of pruritus (P <
      0.001), sicca symptoms (P < 0.001), depression (P < 0.001), fibromyalgia (P <
      0.004), and scleroderma (P < 0.05). For those with varices (P < 0.05) or
      cirrhosis clinically (P < 0.05), higher fatigue scores were noted, although those
      who initially presented with noncirrhotic disease had higher scores at the time
      of testing (P < 0.005). Fatigue was associated with greater use of prescription
      medication (P < 0.01), in particular for antipruritics (cholestyramine: P <
      0.001; rifampin: P < 0.001), proton pump inhibitors (P < 0.002), beta-blockers (P
      < 0.02), and antidepressants (P < 0.001), whereas those taking calcium and
      vitamin D appeared less fatigued (P < 0.05). In a multivariate model, calcium and
      vitamin D use, BMI, stage of disease at diagnosis, as well as symptomatic fatigue
      or pruritus, were significant. Biochemical response to UDCA was not associated
      with lower fatigue scores. CONCLUSION: Attempts at defining the biological basis
      of fatigue in patients with PBC, and improving its treatment, must account for
      its multifactoral causes.

PMID- 20683954
TI  - A smac mimetic reduces TNF related apoptosis inducing ligand (TRAIL)-induced
      invasion and metastasis of cholangiocarcinoma cells.
AB  - Cholangiocarcinoma (CCA) cells paradoxically express tumor necrosis factor
      related apoptosis-inducing ligand (TRAIL), a death ligand that, failing to kill
      CCA cells, instead promotes their tumorigenicity and especially the metastatic
      behaviors of cell migration and invasion. Second mitochondria-derived activator
      of caspase (smac) mimetics are promising cancer therapeutic agents that enhance
      proapoptotic death receptor signaling by causing cellular degradation of
      inhibitor of apoptosis (IAP) proteins. Our aim was to examine the in vitro and in
      vivo effects of the smac mimetic JP1584 in CCA. Despite JP1584-mediated loss of
      cellular inhibitor of apoptosis-1 (cIAP-1) and cIAP-2, TRAIL failed to induce
      apoptosis in KMCH-1, TFK-1, and BDEneu CCA cells; a finding consistent with a
      downstream block in death signaling. Because cIAP-1 and cIAP-2 also promote
      nuclear factor kappa B (NF-kappaB) activation by the canonical pathway, the
      effect of JP1584 on this signaling pathway was examined. Treatment with JP1584
      inhibited TRAIL-induced NF-kappaB activation as well as TRAIL-mediated up
      regulation of the NF-kappaB target gene, matrix metalloproteinase 7 (MMP7).
      JP1584 also reduced TRAIL-mediated CCA cell migration and invasion in vitro.
      Finally, in a syngeneic rat orthotopic CCA model, JP1584 administration reduced
      MMP7 messenger RNA levels and extrahepatic metastases. CONCLUSION: : Although the
      smac mimetic JP1584 does not sensitize cells to apoptosis, it reduces TRAIL
      induced CCA cell metastatic behavior. These data support the emerging concept
      that IAPs are prometastatic and represent targets for antimetastatic therapies.

PMID- 20683956
TI  - Incidence and prevalence of primary sclerosing cholangitis in a defined adult
      population in Sweden.
AB  - Population-based studies on the epidemiology of primary sclerosing cholangitis
      (PSC) are sparse. The aim of the present study was to investigate prevalence and
      temporal trends in the incidence of PSC 1992-2005 in an adult population in
      Vastra Gotaland, a region in southern Sweden with a defined population of about
      1.5 million. Patients with PSC aged 18 years or above were identified through a
      computerized search for diagnostic codes. A total number of 199 incident cases
      fulfilling Mayo criteria for PSC were identified through retrospective validation
      of clinical records. Temporal trends in the incidence of PSC were investigated by
      Poisson regression and expressed as average annual percent change (AAPC) with a
      95% confidence interval (CI). The point prevalence of PSC on December 31, 2005,
      was 16.2/100,000 in the total adult population (men, 23.7/100,000; women,
      8.9/100,000). The annual incidence was 1.22/100,000 in the total adult population
      (men, 1.78/100,000; women, 0.69/100,000). The overall incidence rate of PSC
      increased significantly over the investigation period (AAPC 3.06, 95% CI 0.01
      6.20). Stratified analysis revealed significantly increasing trends for
      inflammatory bowel disease (IBD)-associated PSC (AAPC 7.01, 95% CI 0.24-14.24)
      and large duct PSC (AAPC 6.32, 95% CI 0.03-13.02) in women and for PSC without
      IBD (AAPC 9.69, 95% CI 0.82-19.33) and small duct PSC (AAPC 17.88, 95% CI 0.95
      40.25) in men. CONCLUSION: This is the first study to report a significantly
      increasing trend in the incidence of PSC. The prevalence of PSC at the end of the
      study period is the highest reported to date. This implies that the medical
      burden of PSC may be higher than estimated previously.

PMID- 20683957
TI  - Association between serum uric acid level and chronic liver disease in the United
      States.
AB  - Elevated serum uric acid (UA) levels strongly reflect and may even cause
      oxidative stress, insulin resistance, and metabolic syndrome, which are risk
      factors for the progression of liver disease. We sought to determine whether
      serum UA levels are associated with the development of cirrhosis or the presence
      of elevated serum liver enzymes. We used cohort data from the first National
      Health and Nutrition Examination Survey (NHANES I) to determine whether the
      baseline serum UA level was associated with the incidence of hospitalization or
      death due to cirrhosis among 5518 participants during a mean follow-up of 12.9
      years (range = 4-21 years) after the exclusion of the first 4 years of follow-up.
      We also used cross-sectional data from NHANES 1988-1994 (n = 10,993) and NHANES
      1999-2006 (n = 6186) to determine whether the serum UA level was associated with
      elevated serum alanine aminotransferase (ALT) or gamma-glutamyl transferase
      (GGT), two markers of hepatic necroinflammation. Compared to persons in the lower
      third of the distribution of serum UA (<4.8 mg/dL), those in the top third (>6
      mg/dL) had a higher risk of cirrhosis-related hospitalization or death [adjusted
      hazard ratio (AHR) = 2.8, 95% confidence interval (CI) =1.3-5.7], whereas the
      risk was not substantially increased in persons within the middle third (serum UA
      level = 2.6-4.8 mg/dL, AHR = 1.3, 95% CI = 0.6-2.7). A higher serum UA level was
      associated with greater mean serum ALT and GGT levels and a greater probability
      of elevated serum ALT and GGT. CONCLUSION: The serum UA level is associated with
      the development of cirrhosis and the presence of elevated serum liver enzymes
      after adjustments for important causes and risk factors of chronic liver disease.

PMID- 20683958
TI  - Cytosolic calcium regulates liver regeneration in the rat.
AB  - Liver regeneration is regulated by growth factors, cytokines, and other endocrine
      and metabolic factors. Calcium is important for cell division, but its role in
      liver regeneration is not known. The purpose of this study was to understand the
      effects of cytosolic calcium signals in liver growth after partial hepatectomy
      (PH). The gene encoding the calcium-binding protein parvalbumin (PV) targeted to
      the cytosol using a nuclear export sequence (NES), and using a discosoma red
      fluorescent protein (DsR) marker, was transfected into rat livers by injecting
      it, in recombinant adenovirus (Ad), into the portal vein. We performed two-thirds
      PH 4 days after Ad-PV-NES-DsR or Ad-DsR injection, and liver regeneration was
      analyzed. Calcium signals were analyzed with fura-2-acetoxymethyl ester in
      hepatocytes isolated from Ad-infected rats and in Ad-infected Hela cells. Also,
      isolated hepatocytes were infected with Ad-DsR or Ad-PV-NES-DsR and assayed for
      bromodeoxyuridine incorporation. Ad-PV-NES-DsR injection resulted in PV
      expression in the hepatocyte cytosol. Agonist-induced cytosolic calcium
      oscillations were attenuated in both PV-NES-expressing Hela cells and
      hepatocytes, as compared to DsR-expressing cells. Bromodeoxyuridine incorporation
      (S phase), phosphorylated histone 3 immunostaining (mitosis), and liver mass
      restoration after PH were all significantly delayed in PV-NES rats. Reduced
      cyclin expression and retinoblastoma protein phosphorylation confirmed this
      observation. PV-NES rats exhibited reduced c-fos induction and delayed
      extracellular signal-regulated kinase 1/2 phosphorylation after PH. Finally,
      primary PV-NES-expressing hepatocytes exhibited less proliferation and agonist
      induced cyclic adenosine monophosphate responsive element binding and
      extracellular signal-regulated kinase 1/2 phosphorylation, as compared with
      control cells. CONCLUSION: Cytosolic calcium signals promote liver regeneration
      by enhancing progression of hepatocytes through the cell cycle.

PMID- 20683959
TI  - Human immunodeficiency virus (HIV)-1 infects human hepatic stellate cells and
      promotes collagen I and monocyte chemoattractant protein-1 expression:
      implications for the pathogenesis of HIV/hepatitis C virus-induced liver
      fibrosis.
AB  - Patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus
      (HCV) develop more rapid fibrosis than those infected with HCV only. In HIV/HCV
      coinfected patients, fibrosis progression correlates with HIV RNA levels,
      suggesting a direct role of HIV in liver fibrogenesis. Chemokine (C-C motif)
      receptor 5 (CCR5) and cysteine-X-cysteine receptor 4 (CXCR4), the two major
      coreceptors required for HIV entry into cells, are expressed on activated hepatic
      stellate cells (HSCs), the principle fibrogenic cell type in the liver. We
      therefore examined whether HIV can infect HSCs, explored the potential mechanisms
      of viral entry, and assessed the impact of infection as reflected by the ability
      of HSCs to transfer virus to T lymphocytes and elicit a proinflammatory and
      profibrogenic response. We report that the laboratory-adapted viruses HIV-IIIB
      (CXCR4-tropic or X4) and HIV-BaL (CCR5-tropic or R5) and primary HIV isolates can
      infect both a human stellate cell line, LX-2, and primary human HSCs. HIV entry
      and gene expression in HSCs was confirmed using HIV-green fluorescent protein
      (GFP) expression viral constructs in the presence or absence of the reverse
      transcriptase inhibitor azidothymidine. CD4 expression on a subset of primary
      HSCs was demonstrated using fluorescence-activated cell sorting and
      immunofluorescence staining. Blocking experiments in the presence of anti-CD4,
      anti-CXCR4, and anti-CCR5 revealed that HIV entry into HSCs is predominantly
      CD4/chemokine coreceptor-independent. HIV infection promoted HSC collagen I
      expression and secretion of the proinflammatory cytokine monocyte chemoattractant
      protein-1. Furthermore, infected LX-2 cells were capable of transferring GFP
      expressing virus to T lymphocytes in a coculture system. CONCLUSION: Taken
      together, our results suggest a potential role of HIV in liver
      fibrosis/inflammation mediated through effects on HSCs. The role of early highly
      active antiretroviral therapy initiation in patients with HIV/HCV coinfection
      warrants further investigation.

PMID- 20683960
TI  - Lipid rafts are essential for peroxisome biogenesis in HepG2 cells.
AB  - Peroxisomes are particularly abundant in the liver and are involved in bile salt
      synthesis and fatty acid metabolism. Peroxisomal membrane proteins (PMPs) are
      required for peroxisome biogenesis [e.g., the interacting peroxisomal biogenesis
      factors Pex13p and Pex14p] and its metabolic function [e.g., the adenosine
      triphosphate-binding cassette transporters adrenoleukodystrophy protein (ALDP)
      and PMP70]. Impaired function of PMPs is the underlying cause of Zellweger
      syndrome and X-linked adrenoleukodystrophy. Here we studied for the first time
      the putative association of PMPs with cholesterol-enriched lipid rafts and their
      function in peroxisome biogenesis. Lipid rafts were isolated from Triton X-100
      lysed or Lubrol WX-lysed HepG2 cells and analyzed for the presence of various
      PMPs by western blotting. Lovastatin and methyl-beta-cyclodextrin were used to
      deplete cholesterol and disrupt lipid rafts in HepG2 cells, and this was followed
      by immunofluorescence microscopy to determine the subcellular location of
      catalase and PMPs. Cycloheximide was used to inhibit protein synthesis. Green
      fluorescent protein-tagged fragments of PMP70 and ALDP were analyzed for their
      lipid raft association. PMP70 and Pex14p were associated with Triton X-100
      resistant rafts, ALDP was associated with Lubrol WX-resistant rafts, and Pex13p
      was not lipid raft-associated in HepG2 cells. The minimal peroxisomal targeting
      signals in ALDP and PMP70 were not sufficient for lipid raft association.
      Cholesterol depletion led to dissociation of PMPs from lipid rafts and impaired
      sorting of newly synthesized catalase and ALDP but not Pex14p and PMP70.
      Repletion of cholesterol to these cells efficiently reestablished the peroxisomal
      sorting of catalase but not ALDP. CONCLUSION: Human PMPs are differentially
      associated with lipid rafts independently of the protein homology and/or their
      functional interaction. Cholesterol is required for peroxisomal lipid raft
      assembly and peroxisome biogenesis.

PMID- 20683961
TI  - Quantifying growth and transformation frequency of oncogene-expressing mouse
      hepatocytes in vivo.
AB  - Gene changes can affect cancer cells in many ways, but changes that increase
      disease severity--by allowing cells to proliferate when they should be quiescent,
      by enhancing their rate of growth under growth permissive conditions, or by
      increasing the risk that they will accumulate additional carcinogenic alterations
      -must be identified so that strategies to counter their effects can be developed.
      We describe a novel in vivo assay system based on hepatocyte transplantation that
      permits us to accomplish this objective for genetically modified hepatocytes. We
      find that the oncogenes c-myc and transforming growth factor alpha, but not
      simian virus 40 T-antigen, increase the rate of hepatocyte growth under growth
      permissive conditions. However, no single oncogene can induce hepatocyte growth
      in quiescent liver. In contrast, at least one oncogene combination, transforming
      growth factor alpha/T-antigen, was sufficient to direct cell autonomous growth
      even in this nonpermissive environment. Furthermore, we could quantify risk for
      progression to neoplasia associated with oncogene expression; increased
      transformation frequency was the principal carcinogenic effect of T-antigen.
      CONCLUSION: This system identifies biological mechanistic role(s) in
      carcinogenesis for candidate genetic changes implicated in development of human
      liver cancer. The quantitative and comparative evaluation of gene effects on
      liver cancer allows us to prioritize targets for therapeutic intervention.

PMID- 20683962
TI  - Cytosolic phospholipase A2alpha and peroxisome proliferator-activated receptor
      gamma signaling pathway counteracts transforming growth factor beta-mediated
      inhibition of primary and transformed hepatocyte growth.
AB  - Hepatocellular carcinoma often develops in the setting of abnormal hepatocyte
      growth associated with chronic hepatitis and liver cirrhosis. Transforming growth
      factor beta (TGF-beta) is a multifunctional cytokine pivotal in the regulation of
      hepatic cell growth, differentiation, migration, extracellular matrix production,
      stem cell homeostasis, and hepatocarcinogenesis. However, the mechanisms by which
      TGF-beta influences hepatic cell functions remain incompletely defined. We report
      herein that TGF-beta regulates the growth of primary and transformed hepatocytes
      through concurrent activation of Smad and phosphorylation of cytosolic
      phospholipase A(2)alpha (cPLA(2)alpha), a rate-limiting key enzyme that releases
      arachidonic acid for the production of bioactive eicosanoids. The interplays
      between TGF-beta and cPLA(2)alpha signaling pathways were examined in rat primary
      hepatocytes, human hepatocellular carcinoma cells, and hepatocytes isolated from
      newly developed cPLA(2)alpha transgenic mice. CONCLUSION: Our data show that
      cPLA(2)alpha activates peroxisome proliferator-activated receptor gamma (PPAR
      gamma) and thus counteracts Smad2/3-mediated inhibition of cell growth.
      Therefore, regulation of TGF-beta signaling by cPLA(2)alpha and PPAR-gamma may
      represent an important mechanism for control of hepatic cell growth and
      hepatocarcinogenesis.

PMID- 20683963
TI  - Glycosylation of fibroblast growth factor receptor 4 is a key regulator of
      fibroblast growth factor 19-mediated down-regulation of cytochrome P450 7A1.
AB  - De novo bile acid synthesis in the liver needs to be tightly regulated in order
      to maintain optimal bile flow and prevent cholestasis. In the liver, fibroblast
      growth factor 19 (FGF19) regulates bile acid synthesis by down-regulating
      messenger RNA levels of cytochrome P450 7A1 (CYP7A1). FGF19 acts through
      fibroblast growth factor receptor 4 (FGFR4), and beta-Klotho has recently been
      recognized as a modulator of FGFR4 activity. However, its precise mechanism of
      action has not been thoroughly described. We show here that beta-Klotho is an
      endoplasmic reticulum-resident protein that affects the cellular abundance of
      different FGFR4 glycoforms. beta-Klotho binds and directs the core glycoform of
      FGFR4 to the proteasome, and it allows only a terminal glycoform to reach the
      plasma membrane. Only the terminal FGFR4 glycoform is phosphorylated upon FGF19
      treatment of HepG2 cells, and this shows that only fully glycosylated FGFR4 is
      active in CYP7A1 down-regulation. CONCLUSION: beta-Klotho enhances FGF19
      signaling by binding the inactive, core-glycosylated FGFR4 and preventing it from
      reaching the surface. These results indicate that beta-Klotho is an indirect
      regulator of FGFR4, whereas glycosylation is the master switch for FGF19 activity
      and regulation of bile acid synthesis.

PMID- 20683964
TI  - Biliary secretion of S-nitrosoglutathione is involved in the hypercholeresis
      induced by ursodeoxycholic acid in the normal rat.
AB  - Ursodeoxycholic acid (UDCA) induces bicarbonate-rich hypercholeresis by
      incompletely defined mechanisms that involve the stimulation of adenosine
      triphosphate (ATP) release from cholangiocytes. As nitric oxide (NO) at a low
      concentration can stimulate a variety of secretory processes, we investigated
      whether this mediator could be implicated in the choleretic response to UDCA. Our
      in vivo experiments with the in situ perfused rat liver model in anesthetized
      rats, showed that UDCA infusion increased the biliary secretion of NO
      derivatives, hepatic inducible NO synthase expression, and NO synthase activity
      in liver tissue. UDCA also stimulated NO release by isolated rat hepatocytes. In
      contrast to UDCA, cholic acid was a poor inducer of NO secretion, and
      tauroursodeoxycholic acid showed no effect on NO secretion. Upon UDCA
      administration, NO was found in bile as low-molecular-weight nitrosothiols, of
      which S-nitrosoglutathione (GSNO) was the predominant species. UDCA-stimulated
      biliary NO secretion was abolished by the inhibition of inducible NO synthase
      with N(omega)-nitro-L-arginine methyl ester in isolated perfused livers and also
      in rats whose livers were depleted of glutathione with buthionine sulfoximine.
      Moreover, the biliary secretion of NO species was significantly diminished in
      UDCA-infused transport mutant [ATP-binding cassette C2 (ABCC2)/multidrug
      resistance-associated protein 2 (Mrp2)-deficient] rats, and this finding was
      consistent with the involvement of the glutathione carrier ABCC2/Mrp2 in the
      canalicular transport of GSNO. It was particularly noteworthy that in cultured
      normal rat cholangiocytes, GSNO activated protein kinase B, protected against
      apoptosis, and enhanced UDCA-induced ATP release to the medium; this effect was
      blocked by phosphoinositide 3-kinase inhibition. Finally, retrograde GSNO
      infusion into the common bile duct increased bile flow and biliary bicarbonate
      secretion. CONCLUSION: UDCA induces biliary secretion of GSNO, which contributes
      to stimulating ductal secretion.

PMID- 20683965
TI  - CXC receptor-2 knockout genotype increases X-linked inhibitor of apoptosis
      protein and protects mice from acetaminophen hepatotoxicity.
AB  - Although acetaminophen is a commonly used analgesic, it can be highly
      hepatotoxic. This study seeks to further investigate the mechanisms involved in
      acetaminophen-induced hepatotoxicity and the role of chemokine (C-X-C motif)
      receptor 2 (CXCR2) receptor/ligand interactions in the liver's response to and
      recovery from acetaminophen toxicity. The CXC chemokines and their receptor,
      CXCR2, are important inflammatory mediators and are involved in the control of
      some types of cellular proliferation. CXCR2 knockout mice exposed to a median
      lethal dose of acetaminophen had a significantly lower mortality rate than wild
      type mice. This difference was at least partially attributable to a significantly
      decreased rate of apoptosis in CXCR2 knockout mice versus wild-type mice; there
      were no differences seen in hepatocyte proliferation in wild-type mice versus
      knockout mice after this injury. CONCLUSION: The decreased rate of apoptosis in
      the knockout mice correlated with an almost undetectable and significantly
      decreased level of activated caspase-3 and significantly increased levels of X
      linked inhibitor of apoptosis protein, which also correlated with increased
      levels of nuclear factor kappa B p52 and decreased levels of c-Jun N-terminal
      kinase; this provides a possible mechanism for the decrease in apoptosis seen in
      CXCR2 knockout mice.

PMID- 20683966
TI  - Carbonyl reductase 1 as a novel target of (-)-epigallocatechin gallate against
      hepatocellular carcinoma.
AB  - Human carbonyl reductase 1 (CBR1) converts the antitumor drug and anthracycline
      daunorubicin (DNR) into the alcohol metabolite daunorubicinol (DNROL) with
      significantly reduced antitumor activity and cardiotoxicity, and this limits the
      clinical use of DNR. Inhibition of CBR1 can thus increase the efficacy and
      decrease the toxicity of DNR. Here we report that (-)-epigallocatechin gallate
      (EGCG) from green tea is a promising inhibitor of CBR1. EGCG directly interacts
      with CBR1 and acts as a noncompetitive inhibitor with respect to the cofactor
      reduced nicotinamide adenine dinucleotide phosphate and the substrate isatin. The
      inhibition is dependent on the pH, and the gallate moiety of EGCG is required for
      activity. Molecular modeling has revealed that EGCG occupies the active site of
      CBR1. Furthermore, EGCG specifically enhanced the antitumor activity of DNR
      against hepatocellular carcinoma SMMC7721 cells expressing high levels of CBR1
      and corresponding xenografts. We also demonstrated that EGCG could overcome the
      resistance to DNR by Hep3B cells stably expressing CBR1 but not by RNA
      interference of CBR1-HepG2 cells. The level of the metabolite DNROL was
      negatively correlated with that of EGCG in the cell extracts. Finally, EGCG
      decreased the cardiotoxicity of DNR in a human carcinoma xenograft model with
      both SMMC7721 and Hep3B cells in mice. CONCLUSION: These results strongly suggest
      that EGCG can inhibit CBR1 activity and enhance the effectiveness and decrease
      the cardiotoxicity of the anticancer drug DNR. These findings also indicate that
      a combination of EGCG and DNR might represent a novel approach for hepatocellular
      carcinoma therapy or chemoprevention.

PMID- 20683967
TI  - What is critical for liver surgery and partial liver transplantation: size or
      quality?

PMID- 20683968
TI  - Hepatic lipotoxicity and the pathogenesis of nonalcoholic steatohepatitis: the
      central role of nontriglyceride fatty acid metabolites.
AB  - A significant body of evidence now forces us to rethink the causes of NASH. Once
      thought to be a disease caused by triglyceride accumulation in hepatocytes with
      subsequent oxidant stress and lipid peroxidation causing inflammation and
      fibrosis, new data from animal studies and a limited number of human studies now
      provide convincing evidence that triglyceride accumulation does not cause insulin
      resistance or cellular injury in the liver. The lipotoxic liver injury hypothesis
      for the pathogenesis of NASH suggests that we need to focus our therapeutic
      efforts on reducing the burden of fatty acids going to the liver or being
      synthesized in the liver. This can be accomplished by improving insulin
      sensitivity at the level of adipose tissue to prevent inappropriate peripheral
      lipolysis and by preventing unnecessary de novo lipogenesis in the liver. Excess
      carbohydrates are the major substrates for de novo lipogenesis, and thus,
      reducing carbohydrate consumption through dietary changes and increasing muscle
      glucose uptake through exercise remain important cornerstones of treatment and
      prevention of lipotoxic liver injury, a disease hitherto called NASH.

PMID- 20683969
TI  - Vitamin E for nonalcoholic steatohepatitis: ready for prime time?

PMID- 20683970
TI  - Gut instinct: rifaximin for the prevention of hepatic encephalopathy.

PMID- 20683971
TI  - An unusual cause of acute cholangitis.

PMID- 20683973
TI  - Antituberculosis therapy drug-induced liver injury and acute liver failure.

PMID- 20683975
TI  - Transient elastography in the early prediction of progressive recurrent hepatitis
      C following liver transplantation.

PMID- 20683976
TI  - Targeting heme oxygenase/adiponectin axis for chronic hepatitis C treatment.

PMID- 20683977
TI  - Hepatitis B in refugees, guessing the prevalence.

PMID- 20683978
TI  - The curative efficiency of tenofovir for patients with chronic hepatitis B after
      failure of nucleoside/nucleotide analogues.

PMID- 20683979
TI  - Is cigarette smoking an independent risk factor or a cofactor for nonalcoholic
      fatty liver disease?

PMID- 20683980
TI  - Noonan syndrome associated with both a new Jnk-activating familial SOS1 and a de
      novo RAF1 mutations.
AB  - Noonan syndrome is a genetic condition characterized by congenital heart defects,
      short stature, and characteristic facial features. Familial or de novo mutations
      in PTPN11, RAF1, SOS1, KRAS, and NRAS are responsible for 60-75% of the cases,
      thus, additional genes are expected to be involved in the pathogenesis. In
      addition, the genotype-phenotype correlation has been hindered by the highly
      variable expressivity of the disease. For all these reasons, expanding the
      genotyped and clinically evaluated case numbers will benefit the clinical
      community. A mutation analysis has been performed on RAF1, SOS1, and GRB2, in 24
      patients previously found to be negative for PTPN11 and KRAS mutations. We
      identified four mutations in SOS1 and one in RAF1, while no GRB2 variants have
      been found. Interestingly, the RAF1 mutation was present in a patient also
      carrying a newly identified p.R497Q familial SOS1 mutation, segregating with a
      typical Noonan Syndrome SOS1 cutaneous phenotype. Functional analysis
      demonstrated that the R497Q SOS1 mutation leads to Jnk activation, but has no
      effect on the Ras effector Erk1. We propose that this variant might contribute to
      the onset of the peculiar ectodermal traits displayed by the propositus amidst
      the more classical Noonan syndrome presentation. To our knowledge, this is the
      first reported case of a patient harboring mutations in two genes, with an
      involvement of both Ras and Rac1 pathways, indicating that SOS1 may have a role
      of modifier gene that might contribute the variable expressivity of the disease,
      evidencing a genotype-phenotype correlation in the family.

PMID- 20683981
TI  - Unexpected detection of dystrophin gene deletions by array comparative genomic
      hybridization.
AB  - Array comparative genomic hybridization has increasingly become the standard of
      care to evaluate patients for genomic imbalance. As the patient population
      evaluated by microarray expands, there is certain to be an increase in the
      detection of unexpected, yet common diseases. When array results predict a late
      onset disorder or cancer predisposition, it becomes a challenge for physicians
      and counselors to adequately address with patients. Included in this study were
      three patients described with nonspecific phenotypic findings who underwent
      microarray testing to better define their disease etiology. An unexpected
      deletion within the dystrophin gene was observed in each case, despite that no
      patient was suspected of a dystrophinopathy at the time of testing. The patients
      included an 8-day-old male with a dystrophin deletion predictive of Becker
      muscular dystrophy, an 18-month old female found to be the carrier of deletion,
      and a 4-year-8-month-old male with a deletion predictive of Duchenne muscular
      dystrophy. In this circumstance it becomes difficult to counsel the family, as
      well as to predict disease course when underlying medical conditions may exist.
      However, early detection may enable the patient to receive proactive treatment,
      and allows for screening of at-risk family members. Ultimately, it is up to the
      clinician to promote informed decision-making within the family prior to testing,
      and ensure that adequate counseling is provided during follow-up.

PMID- 20683982
TI  - The mystery of Williams-Beuren syndrome associated with pulmonary dysfunction,
      sudden death, and Kounis syndrome.

PMID- 20683983
TI  - Description of the smallest critical region for Dandy-Walker malformation in
      chromosome 13 in a girl with a cryptic deletion related to t(6;13)(q23;q32).
AB  - We report on a girl with mild dysmorphic facial features, Dandy-Walker
      malformation (DWM), iris coloboma, profound hearing loss, and hyperlaxity of skin
      and joints, whose karyotype is 46,XX,t(6;13)(q23;q32)dn and who has a cryptic
      imbalance at the 13q32 translocation breakpoint assessed by array-CGH. Our
      patient has many clinical manifestations in common with those of the previously
      reported cases of 13q32 deletions, which suggests that at least part of the
      abnormal phenotype is probably due to the imbalance. The recurrent finding of DWM
      among patients with 13q deletions has led to the suggestions that candidate
      gene/s for its development are on chromosome 13. We describe the smallest 13q
      deletion associated to DWM, which allows further narrowing of the previously
      established critical region for this brain malformation to 13q32.2-32.3. Among
      the few genes of the deleted region, ZIC2 and ZIC5 seem the most plausible
      candidates, which is in keeping with some previous reports. This work also
      illustrates the usefulness of array-CGH platforms in the identification of
      cryptic imbalances in carriers of apparently balanced rearrangements with
      abnormal phenotypes.

PMID- 20683984
TI  - Autosomal dominant syndrome of camptodactyly, clinodactyly, syndactyly, and bifid
      toes.
AB  - We report on a 25-year follow-up of a Pakistani kindred with a unique combination
      of camptodactyly and clinodactyly of 5th fingers, mesoaxial camptodactyly of
      toes, and ulnar deviation of 3rd fingers. The less common anomalies in the
      affected subjects include syndactyly involving all digits, and bifid toes. This
      condition is grossly bilateral, symmetrical, and affects upper and lower limbs of
      the 26 affected subjects in the kindred. The comparable number of affected male
      and female subjects (chi(2) = 0.154, P < 0.1), disease allele transmission by
      mother and father, and the malformation segregation in four consecutive
      generations are strongly suggestive of autosomal dominant inheritance.
      Differential diagnosis considered syndactyly types II, III, and V. Only type II
      syndactyly manifests noticeable phenotypic overlap with the clinical presentation
      in this family; however, the typical type II syndactyly changes are absent. To
      the best of our knowledge, this autosomal dominant limb phenotype has not been
      reported previously.

PMID- 20683985
TI  - Identification of genomic loci contributing to agenesis of the corpus callosum.
AB  - Agenesis of the corpus callosum (ACC) is a common brain malformation of variable
      clinical expression that is seen in many syndromes of various etiologies.
      Although ACC is predominantly genetic, few genes have as yet been identified. We
      have constructed and analyzed a comprehensive map of ACC loci across the human
      genome using data generated from 374 patients with ACC and structural chromosome
      rearrangements, most having heterozygous loss or gain of genomic sequence and a
      few carrying apparently balanced rearrangements hypothesized to disrupt key
      functional genes. This cohort includes more than 100 previously unpublished
      patients. The subjects were ascertained from several large research databases as
      well as the published literature over the last 35 years. We identified 12 genomic
      loci that are consistently associated with ACC, and at least 30 other recurrent
      loci that may also contain genes that cause or contribute to ACC. Our data also
      support the hypothesis that many ACC loci confer susceptibility to other brain
      malformations as well as ACC, such as cerebellar hypoplasia, microcephaly, and
      polymicrogyria. The database presented here provides a valuable resource for
      diagnosis and management of individuals with ACC and individuals with chromosome
      rearrangements in whom ACC should be suspected, and of course for identifying ACC
      causal and contributory genes. Well-defined diagnostic criteria, improved
      scanning techniques, and increased recognition of associated abnormalities will
      further facilitate gene mapping and allow definition of distinct syndromes within
      this heterogeneous group of patients.

PMID- 20683986
TI  - A novel de novo microdeletion spanning the SYNGAP1 gene on the short arm of
      chromosome 6 associated with mental retardation.

PMID- 20683987
TI  - Copy number variation analysis in single-suture craniosynostosis: multiple rare
      variants including RUNX2 duplication in two cousins with metopic
      craniosynostosis.
AB  - Little is known about genes that underlie isolated single-suture
      craniosynostosis. In this study, we hypothesize that rare copy number variants
      (CNV) in patients with isolated single-suture craniosynostosis contain genes
      important for cranial development. Using whole genome array comparative genomic
      hybridization (CGH), we evaluated DNA from 186 individuals with single-suture
      craniosynostosis for submicroscopic deletions and duplications. We identified a
      1.1 Mb duplication encompassing RUNX2 in two affected cousins with metopic
      synostosis and hypodontia. Given that RUNX2 is required as a master switch for
      osteoblast differentiation and interacts with TWIST1, mutations in which also
      cause craniosynostosis, we conclude that the duplication in this family is
      pathogenic, albeit with reduced penetrance. In addition, we find that a total of
      7.5% of individuals with single-suture synostosis in our series have at least one
      rare deletion or duplication that contains genes and that has not been previously
      reported in unaffected individuals. The genes within and disrupted by CNVs in
      this cohort are potential novel candidate genes for craniosynostosis.

PMID- 20683988
TI  - Gene expression patterns in the bone tissue of women with fibrous dysplasia.
AB  - Fibrous dysplasia is an isolated skeletal disorder caused by a somatic activating
      mutation of GNAS gene with abnormal unmineralized matrix overproduction and
      extensive undifferentiated bone cell accumulation in the fibro-osseous lesions.
      The aim of our investigation was to identify genes that are differently expressed
      in fibrous versus non-fibrous human bone and to describe the relationships
      between these genes using multivariate data analysis. Six bone tissue samples
      from female patients with fibrous dysplastia (FD) and seven bone tissue samples
      from women without FD (non-FD) were examined. The expression differences of
      selected 118 genes were analyzed by the TaqMan probe-based quantitative real-time
      RT-PCR system. The Mann-Whitney U-test indicated marked differences in the
      expression of 22 genes between FD and non-FD individuals. Nine genes were
      upregulated in FD women compared to non-FD ones and 18 genes showed a
      downregulated pattern. These altered genes code for minor collagen molecules,
      extracellular matrix digesting enzymes, transcription factors, adhesion
      molecules, growth factors, pro-inflammatory cytokines, and lipid metabolism
      affected substrates. Canonical variates analysis demonstrated that FD and non-FD
      bone tissues can be distinguished by the multiple expression profile analysis of
      numerous genes controlled via a G-protein coupled pathway and BMP cascade as well
      as genes coding for extracellular matrix composing molecules. The remarkable
      changed gene expression profile observed in the fibrous dysplastic human bone
      tissue may provide further insight into the pathogenetic process of fibrous
      degeneration of bone.

PMID- 20683989
TI  - A mutation in PEX19 causes a severe clinical phenotype in a patient with
      peroxisomal biogenesis disorder.
AB  - Peroxisomal biogenesis disorders (PBD) are groups of inherited neurometabolic
      disorders caused by defects in PEX genes. We report on a female infant, born to a
      consanguineous parents (first degree cousins), who presented with inactivity,
      poor sucking, and hypotonia early in the neonatal period. She had subtle
      dysmorphic features. Liver function tests were impaired with raised liver
      enzymes, conjugated and unconjugated hyperbilirubinemia. CT of the brain showed
      diffuse bilateral changes. She developed seizures with an abnormal EEG. Plasma
      very long chain fatty acid analysis showed high C26:0 levels and
      increasedC26:0/C22:0 and C24:0/C22:0 ratios, which is consistent with a PBD.
      Studies in fibroblasts including plasmalogen biosynthesis, peroxisomal fatty acid
      alfa and beta oxidation confirmed the diagnosis of PBD. Immunofluoresence
      microscopy revealed the absence of peroxisomes in fibroblasts. The patient was
      assigned to the PEX19 complementation group. Subsequent mutation analysis of the
      PEX19 gene revealed homozygosity for a c.320delA frameshift mutation. The patient
      had a stormy course with multiple admissions to the pediatric intensive care unit
      with pneumonia, liver impairment, sepsis, and epilepsy. At 1 year of age she
      developed metabolic acidosis with normal anion gap, proteinuria, aminoaciduria,
      and glucosuria consistent with a renal tubular defect. Abdominal ultrasound
      showed multiple gallstones. Other causes of gallstones like haemoglobinopathy
      were excluded. So far, only two siblings had been reported with mutations in the
      PEX19 gene. Our patient showed a previously unrecognized association of
      gallstones and a renal tubular defect with a PBD.

PMID- 20683990
TI  - Phenotypic spectrum of 20 novel patients with molecularly defined supernumerary
      marker chromosomes 15 and a review of the literature.
AB  - Supernumerary marker chromosomes (SMC) originating from chromosome 15 are the
      most common SMCs. They encompass clinically irrelevant SMC(15)s containing only
      heterochromatin and 15p material, and clinically relevant SMC(15)s that consist
      of both eu- and heterochromatic 15q material. On the basis of size, the
      clinically relevant SMC(15)s can be subdivided into type A, "large" asymmetric
      and type B, "small" symmetric SMC(15)s. Type B SMC(15)s contain the triplicated
      15pter to BP3 (located at 26.5 Mb) region, while type A SMC(15)s consist of
      15pter --> BP4(28.5 Mb)::BP5(30.5 Mb) --> 15pter. In this study, the clinical and
      molecular features of 18 patients with A and B SMC(15)s and two patients with a
      partial trisomy 15q were reviewed. Questionnaires (including Child Behavior Check
      Lists) were used to assess behavior and developmental features in more detail.
      The marker size and parental origin were determined by multiplex ligation
      dependent probe amplification (MLPA). Based on the MLPA results, the majority of
      patients (14/18) had type A SMC(15)s. The phenotype observed did not show
      significant differences between types A and B SMC(15)s. A high prevalence of
      autistic-like behavior, attention problems, aggressive behavior, anxiety, and
      sleeping problems was reported. Motor and speech development varied extensively
      among the patients. An association was found between positive seizure history and
      degree of intellectual disability.

PMID- 20683991
TI  - Transient QT interval prolongation in an infant with Simpson-Golabi-Behmel
      syndrome.

PMID- 20683992
TI  - Microdeletion of 16p11.2 associated with endocardial fibroelastosis.

PMID- 20683993
TI  - Mosaic compound heterozygosity of SHOX resulting in Leri-Weill dyschondrosteosis
      with marked short stature: implications for disease mechanisms and recurrence
      risks.
AB  - Mutations or deletions in the SHOX gene cause Leri-Weill dyschondrosteosis (LWD)
      and Langer mesomelic dysplasia (LMD) when present in heterozygous or homozygous
      form, respectively. A new class of enhancer deletions was identified 30-250 kb
      downstream of SHOX. We identified a female patient with marked short stature,
      mosaic for monosomy X in 31% of her lymphocytes, and findings consistent with
      LWD. Additional molecular studies demonstrated segregation of 17 polymorphic
      markers flanking and including the SHOX locus, spanning 328 kb of pseudoautosomal
      region 1 (PAR1) region. A deletion up to 10 kb residing 197 kb downstream of SHOX
      gene was detected, which was germinally transmitted from her clinically
      unaffected father. This was associated with post-zygotic mosaic loss of the
      normal maternal X-chromosome, evidenced by fluorescent fragment analysis. Since
      most patients with LMD with deletions downstream of SHOX gene also have SHOX
      mutations in trans, it may suggest these deletions are associated with a milder
      phenotype. Further studies are required to elucidate the role of the former
      region in disease etiology. Mutations should be sought in clinically non-affected
      family members because of the variable expressivity in hemizygous carriers, and
      cytogenetic evaluation should be considered to detect possible X-chromosome
      rearrangements underlying the haploinsufficiency for the PAR1 when deletion is
      detected by molecular analysis. Similarly, when LWD and marked short stature
      occur in a patient with mosaic Turner syndrome, the possibility of mutations in
      SHOX and the downstream of SHOX gene should be considered.

PMID- 20683994
TI  - Congenital portosystemic shunt in a child with Wolf-Hirschhorn syndrome.

PMID- 20683995
TI  - Cerebellar hypoplasia and Cohen syndrome: a confirmed association.

PMID- 20683996
TI  - A family with a 1.17 Mb deletion of 12q12: refining genotype-phenotype
      correlation.

PMID- 20683997
TI  - Large deletions and uniparental disomy detected by SNP arrays in adults with
      thoracic aortic aneurysms and dissections.

PMID- 20683998
TI  - Analysis of component findings in 79 patients diagnosed with VACTERL association.
AB  - VACTERL association is a relatively common condition, though the causes remain
      poorly understood. We present data on 79 patients diagnosed with VACTERL
      association and perform statistical analysis on a selected subset of 60 patients
      with at least three component features, and who, after review, did not meet
      criteria for a likely alternate diagnosis. Considered individually, no two
      component features are significantly associated, but several multivariate
      statistical techniques suggest novel patterns of the co-occurrence of component
      features, and latent class cluster analysis demonstrates the presence of five
      major subgroups of patients. These findings have implications for both our
      understanding of VACTERL association and for the approach to research involving
      this condition.

PMID- 20683999
TI  - Temple-Baraitser syndrome: a rare and possibly unrecognized condition.
AB  - Temple-Baraitser syndrome, previously described in two unrelated patients, is the
      association of severe mental retardation and abnormal thumbs and great toes. We
      report two additional unrelated patients with Temple-Baraitser syndrome, review
      clinical and radiological features of previously reported cases and discuss mode
      of inheritance. Patients share a consistent pattern of anomalies: hypo or aplasia
      of the thumb and great toe nails and broadening and/or elongation of the thumbs
      and halluces, which have a tubular aspect. All patients were born to unrelated
      parents and occurred as a single occurrence in multiple sibships, suggesting
      sporadic inheritance from a de novo mutation mechanism. Comparative genomic
      hybridization in Patients 1, 2 and 3 did not reveal any copy number variations.
      We confirm that Temple-Baraitser syndrome represents a distinct syndrome,
      probably unrecognized, possibly caused by a de novo mutation in a not yet
      identified gene.

PMID- 20684000
TI  - Mental retardation, growth retardation, unusual nose, and open mouth: an
      autosomal recessive entity.
AB  - In this paper, I describe the investigations in three members of an extended
      consanguineous family from Saudi Arabia, in which nine members show severe mental
      retardation, long eyelashes, high nasal bridge, underdeveloped malae, low hanging
      columella, thin upper vermillion, and everted lower vermillion, retrognathia, and
      an open mouth apparently caused by mandibular dentoalveolar protrusion. Pedigree
      analysis makes it likely that this is an autosomal recessively inherited
      disorder. A detailed literature search failed to show a similar entity.

PMID- 20684001
TI  - Progressive spastic paraplegia as a feature of tetrasomy 18p.

PMID- 20684002
TI  - Inhibitory effects of megakaryocytic cells in prostate cancer skeletal
      metastasis.
AB  - Prostate cancer cells commonly spread through the circulation, but few
      successfully generate metastatic foci in bone. Osteoclastic cellular activity has
      been proposed as an initiating event for skeletal metastasis. Megakaryocytes
      (MKs) inhibit osteoclastogenesis, which could have an impact on tumor
      establishment in bone. Given the location of mature MKs at vascular sinusoids,
      they may be the first cells to physically encounter cancer cells as they enter
      the bone marrow. Identification of the interaction between MKs and prostate
      cancer cells was the focus of this study. K562 (human MK precursors) and primary
      MKs derived from mouse bone marrow hematopoietic precursor cells potently
      suppressed prostate carcinoma PC-3 cells in coculture. The inhibitory effects
      were specific to prostate carcinoma cells and were enhanced by direct cell-cell
      contact. Flow cytometry for propidium iodide (PI) and annexin V supported a
      proapoptotic role for K562 cells in limiting PC-3 cells. Gene expression analysis
      revealed reduced mRNA levels for cyclin D1, whereas mRNA levels of apoptosis
      associated specklike protein containing a CARD (ASC) and death-associated protein
      kinase 1 (DAPK1) were increased in PC-3 cells after coculture with K562 cells.
      Recombinant thrombopoietin (TPO) was used to expand MKs in the marrow and
      resulted in decreased skeletal lesion development after intracardiac tumor
      inoculation. These novel findings suggest a potent inhibitory role of MKs in
      prostate carcinoma cell growth in vitro and in vivo. This new finding, of an
      interaction of metastatic tumors and hematopoietic cells during tumor
      colonization in bone, ultimately will lead to improved therapeutic interventions
      for prostate cancer patients.

PMID- 20684003
TI  - Congenital generalized lipodystrophy, type 4 (CGL4) associated with myopathy due
      to novel PTRF mutations.
AB  - Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disorder
      characterized by near total absence of body fat since birth with predisposition
      to insulin resistance, diabetes, hypertriglyceridemia, and hepatic steatosis.
      Three CGL loci, AGPAT2, BSCL2, and CAV1, have been identified previously.
      Recently, mutations in polymerase I and transcript release factor (PTRF) were
      reported in five Japanese patients presenting with myopathy and CGL (CGL4). We
      report novel PTRF mutations and detailed phenotypes of two male and three female
      patients with CGL4 belonging to two pedigrees of Mexican origin (CGL7100 and
      CGL178) and one pedigree of Turkish origin (CGL180). All patients had near total
      loss of body fat and congenital myopathy manifesting as weakness, percussion
      induced muscle mounding, and high serum creatine kinase levels. Four of them had
      hypertriglyceridemia. Three of them had atlantoaxial instability. Two patients
      belonging to CGL178 pedigree required surgery for pyloric stenosis in the first
      month of life. None of them had prolonged QT interval on electrocardiography but
      both siblings belonging to CGL7100 had exercise-induced ventricular arrhythmias.
      Three of them had mild acanthosis nigricans but had normal glucose tolerance. Two
      of them had hepatic steatosis. All patients had novel null mutations in PTRF
      gene. In conclusion, mutations in PTRF result in a novel phenotype that includes
      generalized lipodystrophy with mild metabolic derangements, myopathy, cardiac
      arrhythmias, atlantoaxial instability, and pyloric stenosis. It is unclear how
      mutations in PTRF, which plays an essential role in formation of caveolae, affect
      a wide variety of tissues resulting in a variable phenotype.

PMID- 20684005
TI  - Complex rearrangements between chromosomes 6, 10, and 11 with multiple deletions
      at breakpoints.
AB  - Here we report on a girl with minor facial anomalies, cleft palate, seizures,
      microcephaly, psychomotor retardation, and a congenital heart defect. Complex of
      cytogenetic methods [GTG-banding, spectral karyotyping (SKY), fluorescence in
      situ hybridization (FISH), multicolor banding (mBAND), and comparative genomic
      hybridization (array CGH)] showed complex chromosomal rearrangements (CCRs)
      involving chromosomes 6, 10, and 11 and 4 deletions at the breakpoints. Her
      father had an unrelated translocation between chromosomes 3 and 16, suggesting
      the possibility of an autosomal dominant trait that predisposes to complex
      synapses and recombination between multiple chromosomes during meiosis. This
      study demonstrates the power of combining available chromosome analysis
      technologies in resolving CCR.

PMID- 20684004
TI  - Regulation of facial morphogenesis by endothelin signaling: insights from mice
      and fish.
AB  - Craniofacial morphogenesis is accomplished through a complex set of developmental
      events, most of which are initiated in neural crest cells within the pharyngeal
      arches. Local patterning cues from the surrounding environment induce gene
      expression within neural crest cells, leading to formation of a diverse set of
      skeletal elements. Endothelin-1 (Edn1) is one of the primary signals that
      establishes the identity of neural crest cells within the mandibular portion of
      the first pharyngeal arch. Signaling through its cognate receptor, the endothelin
      A receptor, is critical for patterning the ventral/distal portion of the arch
      (lower jaw) and also participates with Hox genes in patterning more posterior
      arches. Edn1/Ednra signaling is highly conserved between mouse and zebrafish, and
      genetic analyses in these two species have provided complementary insights into
      the patterning cues responsible for establishing the craniofacial complex as well
      as the genetic basis of facial birth defect syndromes.

PMID- 20684006
TI  - Interval estimation for the area under the receiver operating characteristic
      curve when data are subject to error.
AB  - The area (A) under the receiver operating characteristic curve is commonly used
      to quantify the ability of a biomarker to correctly classify individuals into two
      populations. However, many markers are subject to measurement error, which must
      be accounted for to prevent understating their effectiveness. In this paper, we
      develop a new confidence interval procedure for A which is adjusted for
      measurement error using either external or internal replicated measurements.
      Based on the observation that A is a function of normal means and variances, we
      develop the procedure by recovering variance estimates needed from confidence
      limits for normal means and variances. Simulation results show that the procedure
      performs better than the previous ones based on the delta-method in terms of
      coverage percentage, balance of tail errors and interval width. Two examples are
      presented.

PMID- 20684007
TI  - Cranio-meta-diaphyseal dysplasia: 25 year follow-up and review of literature.
AB  - We report here on a 25-year follow-up of cranio-meta-diaphyseal dysplasia in a 31
      year-old Caucasian male, who was reported in the literature at the age of 8 years
      [Langer et al. (1991); Skeletal Radiol 20:37-41]. He has hyperostotic
      craniofacial features with protruding lower jaw and midface hypoplasia. He has
      the typical radiographic features of wide long tubular bones without normal
      metaphyseal flaring and wide short tubular bones without normal diaphyseal
      constriction. We describe here his clinical and radiological findings and compare
      his case with those published in the literature. He is the oldest reported
      patient with this disorder giving some insight into the natural history of this
      rare skeletal dysplasia.

PMID- 20684008
TI  - Ehlers-Danlos syndrome hypermobility type and the excess of affected females:
      possible mechanisms and perspectives.

PMID- 20684009
TI  - Cancer in Crohn's Disease patients treated with infliximab: a long-term
      multicenter matched pair study.
AB  - BACKGROUND: The long-term risk of neoplasia in Crohn's disease (CD) patients
      treated with infliximab is undefined. The aim was to assess, in a multicenter,
      matched-pair study, whether infliximab use in CD is associated with an increased
      frequency of neoplasia in the long term. METHODS: A multicenter, long-term,
      matched-pair study was conducted in 12 referral inflammatory bowel disease (IBD)
      centers. An initial cohort of 808 CD patients, including 404 infliximab-treated
      (CD-IFX) and 404 matched CD controls never treated with infliximab (CD-C) studied
      from 1999 to 2004, was followed up for an additional 4 years (2004-2008). Cases
      and controls were matched for: sex, age (+/-5 years), CD site, follow-up (+/-5
      years), immunosuppressant use, and CD duration (+/-5 years). From 1999 to 2008
      the frequency and characteristics of neoplasia were compared between CD-IFX and
      CD-C. RESULTS: In 2008, 591 patients (304 CD-IFX, 287 CD-C) were in follow-up.
      Matched couples included 442 patients: 221 CD-IFX and 221 CD-C (median follow-up,
      months: 72, range 48-114 versus 75, range 44-114). From 1999 to 2008 the
      frequency of neoplasia among the 591 patients did not differ between CD-IFX
      (12/304; 3.94%) and CD-C (12/287; 4.19%; P = 0.95). A comparable frequency of
      neoplasia was also observed between the 221 matched couples (CD-IFX: 8/221; 3.61%
      versus CD-C: 9/221; 4.07%; P = 1). No specific histotype of cancer appeared
      associated with infliximab use. CONCLUSIONS: The frequency of neoplasia was
      comparable in an adult population of CD patients treated or not with infliximab,
      matched for clinical variables and followed up for a median of 6 years.

PMID- 20684010
TI  - A prenatally recognizable malformation syndrome associated with a recurrent post
      zygotic chromosome rearrangement der(Y)t(Y;1)(q12:q21).
AB  - Several cases of mos 46,X,der(Y)t(Y;1)(q12;q21)/46,XY with multiple anomalies
      have been reported. I report on an additional case of a male fetus with a mosaic
      male karyotype mos 46,X,der(Y)t(Y;1)(q12;q21)[31]/46,XY[21] and multiple
      anomalies that included "teardrop"-shaped head with a triangular face, a short
      nasal bridge with upturned nose, microretrognathia, microtia, kyphoscoliosis,
      oligodactyly, syndactyly, joint contractures, CNS malformation, omphalocele,
      diaphragmatic hernia, cardiac anomaly, and urogenital malformation. The findings
      together suggest a recurrent and recognizable syndrome and argue for using
      tissues such as skin or cartilage or amniotic fluid, instead of cord blood, for
      postmortem karyotyping in order to avoid missing mosaicism as a potential cause
      of multiple congenital anomalies.

PMID- 20684011
TI  - Atypical Silver-Russell phenotype resulting from maternal uniparental disomy of
      chromosome 7.
AB  - We report on a patient with atypical Silver-Russell phenotype comprising severe
      growth retardation, unusual facies, bilateral Duane anomaly and infantile
      hypercalcemia caused by maternal uniparental iso/heterodisomy (mUPD) of
      chromosome 7. The development of myoclonus in this patient lends further support
      to the hypothesis that abnormal imprinting of the SGCE gene is responsible for
      some cases of myoclonus-dystonia syndrome. This case highlights the utility of
      SNP microarray technology as an accessible tool for the diagnosis of mUPD7 in
      atypical cases. We propose that depending on the balance of iso- and
      heterodisomic segments in a particular patient, mUPD7 may result in a range of
      phenotypes not confined to classic Silver-Russell syndrome.

PMID- 20684012
TI  - Immediate and long-term outcomes of corticosteroid therapy in pediatric Crohn's
      disease patients.
AB  - BACKGROUND: Although a mainstay of treatment of moderate to severe Crohn's
      disease (CD), corticosteroids use presents significant challenges because of
      large interindividual variability in response. Corticosteroid-dependence is of
      particular concern in children, where high rates have been reported. We examined
      the burden of corticosteroid-resistance and dependence in a well-characterized
      cohort of pediatric CD patients and investigated potential predictors of
      response. METHODS: Children diagnosed with CD (<18 years), were recruited from
      two Canadian pediatric gastroenterology clinics. Immediate and long-term
      responses to corticosteroid therapy were retrospectively ascertained. Response
      rates (resistance and dependence) were estimated and potential predictors
      assessed using logistic regression analysis. RESULTS: Of the 645 CD patients, 364
      (56.2%) received corticosteroids. The frequency of corticosteroid-resistance was
      (8.0%) (95% confidence interval [CI]: 5.0%-11%) and 40.9% (95% CI: 39.0%-46.0%)
      became dependent. In univariate analysis female gender (odds ratio [OR] = 2.49,
      95% CI: 1.1-5.5, P = 0.025), disease severity (OR = 2.43, 95% CI: 1.10-5.38, P =
      0.029), and complicated disease (OR = 2.75, 95% CI: 1.18-6.41, P = 0.019) were
      associated with resistance. In multivariate analysis lower age at diagnosis (OR =
      1.34,95% CI: 1.03-3.01, P = 0.040), coexisting upper digestive tract involvement
      (OR = 1.35, 95% CI: 1.06-3.07, P = 0.031), and concomitant immunomodulator use
      (OR = 0.35, 95% CI: 0.16-0.75, P = 0.007) were significantly associated with
      steroid dependency. CONCLUSIONS: Our results demonstrate that steroid dependency
      is a frequent complication in children with CD. Children with an earlier age at
      diagnosis and coexisting upper digestive tract involvement could be potentially
      targeted for steroid-sparing therapy.

PMID- 20684013
TI  - Inheritance and variable expression in Rubinstein-Taybi syndrome.
AB  - Familial Rubinstein-Taybi syndrome (RTS) is very rare. Here we report on the 6th
      and 7th case of inherited RTS. Family 1 presents with incomplete or mild RTS over
      three generations; a 13-year-old girl (proband 1) with mild but typical facial
      features and learning disabilities, her very mildly affected mother (proband 2),
      and the maternal grandmother (proband 3). Family 2 includes three females with
      classical RTS (probands 4-6) and their father (proband 7) with broad thumbs and
      halluces. Proband 5 also had a brain tumor (ganglioglioma) at the age of 3 years.
      In probands 1-3, direct sequencing identified a novel CREBBP missense mutation,
      c.2728A > G (predicting p.Thr910Ala), that was absent in non-affected family
      members. The p.Thr910Ala variant is outside the crucial histone acetyltransferase
      domain, and this may explain the mild and variable phenotype. In probands 4-7 we
      identified another novel CREBBP mutation, c.4134G > T, which alters the consensus
      splice sequence at position 1 of exon 25. The c.4134G > T mutation was
      transmitted from the very mildly affected father who displayed somatic mosaicism
      (with 38% mutated alleles in blood and 31% in buccal smear DNA) to his three
      daughters. Our findings emphasize that variable expression (family 1) and somatic
      mosaicism (family 2) contribute to the phenotypic variability of RTS. Somatic
      mosaicism may be more frequent in RTS than previously assumed. Accumulating data
      suggest a recurrence risk of approximately 0.5-1% for parents of a child with
      RTS, exceeding the so far estimated risk of approximately 0.1% for siblings.

PMID- 20684014
TI  - Is Crohn's creeping fat an adipose tissue?
AB  - BACKGROUND: In human pathology, the "creeping fat" (CF) of the mesentery is
      unique to Crohn's disease (CD). CF is usually referred to as an ectopic extension
      of mesenteric adipose tissue (MAT). However, since no animal model developing CF
      has ever been established, very little is known about this type of fat-depot
      expansion and its role in the development of the disease. METHODS: We developed
      and standardized an experimental protocol in mice that reproducibly induces CF
      development when a severe colonic inflammation is obtained by intracolonic
      instillation of DNBS. RESULTS: Macro-microscopic observations revealed a fatty
      appearance of CF. Yet when compared to MAT from the same animals, CF contains
      very little triglycerides, few adipocytes, and we observed a very low expression
      and protein levels of both adipose markers (hormone-sensitive lipase, perilipin)
      and adipocytokines (leptin, adiponectin). The decreased expression of perilipin
      in CF was also observed by immunohistochemistry. Conversely, the expression of
      proinflammatory and fibrous markers (Pref-1) was much higher in CF than in MAT.
      These observations were fully consistent with those made on CF recovered from
      five CD patients and compared with subcutaneous and mesenteric fat from the same
      patients. CONCLUSIONS: Altogether, this work reports an original experimental
      mice model of CF. In this model we establish for the first time that CF only
      occurs in severe colonic inflammation and shows an inflammatory, fibrous but not
      an adipose pattern.

PMID- 20684015
TI  - Paracentric inversion of chromosome 2 associated with cryptic duplication of 2q14
      and deletion of 2q37 in a patient with autism.
AB  - We describe a patient with autism and a paracentric inversion of chromosome
      2q14.2q37.3, with a concurrent duplication of the proximal breakpoint at
      2q14.1q14.2 and a deletion of the distal breakpoint at 2q37.3. The abnormality
      was derived from his mother with a balanced paracentric inversion. The inversion
      in the child appeared to be cytogenetically balanced but subtelomere FISH
      revealed a cryptic deletion at the 2q37.3 breakpoint. High-resolution single
      nucleotide polymorphism array confirmed the presence of a 3.5 Mb deletion that
      extended to the telomere, and showed a 4.2 Mb duplication at 2q14.1q14.2. FISH
      studies using a 2q14.2 probe showed that the duplicated segment was located at
      the telomeric end of chromosome 2q. This recombinant probably resulted from
      breakage of a dicentric chromosome. The child had autism, mental retardation,
      speech and language delay, hyperactivity, growth retardation with growth hormone
      deficiency, insulin-dependent diabetes, and mild facial dysmorphism. Most of
      these features have been previously described in individuals with simple terminal
      deletion of 2q37. Pure duplications of the proximal chromosome 2q are rare and no
      specific syndrome has been defined yet, so the contribution of the 2q14.1q14.2
      duplication to the phenotype of the patient is unknown. These findings underscore
      the need to explore apparently balanced chromosomal rearrangements inherited from
      a phenotypically normal parent in subjects with autism and/or developmental
      delay. In addition, they provide further evidence indicating that chromosome 2q
      terminal deletions are among the most frequently reported cytogenetic
      abnormalities in individuals with autism.

PMID- 20684016
TI  - Irritable pouch syndrome is characterized by visceral hypersensitivity.
AB  - BACKGROUND: Irritable pouch syndrome (IPS) is a functional disorder in patients
      with ileal pouch-anal anastomosis (IPAA), which presents with symptoms in the
      absence of structural abnormalities of the pouch. Thus, it resembles other
      functional disorders, such as irritable bowel syndrome characterized by visceral
      hypersensitivity in the presence of normal rectal biomechanics. The aim was to
      assess pouch biomechanics and perception of balloon distension in different
      groups of subjects with IPAA and to correlate the findings with clinical
      features. METHODS: Pouch tone, compliance, and sensation to balloon distension
      were measured in 18 patients with IPS, 11 patients with active pouch inflammation
      (pouchitis or Crohn's disease of the pouch), and 12 asymptomatic subjects with
      normal pouches. All patients were recruited from a subspecialty Pouchitis Clinic.
      RESULTS: Scores of sensation of gas, urge to defecate, and pain measured by
      visual analog scales at various distension pressures were significantly higher in
      IPS than pouchitis and normal pouch patients. Pouch tone was comparable among the
      groups and compliance was reduced in the pouchitis group. The visual analog scale
      showed a trend of correlation with the Pouchitis Disease Activity Index symptom
      scores in IPS. CONCLUSIONS: IPS, like other gut functional disorders, is
      characterized by visceral hypersensitivity, with normal pouch biomechanics.

PMID- 20684017
TI  - Tocotrienols have potent antifibrogenic effects in human intestinal fibroblasts.
AB  - BACKGROUND: Excessive fibroblast expansion and extracellular matrix (ECM)
      deposition are key events for the development of bowel stenosis in Crohn's
      disease (CD) patients. Tocotrienols are vitamin E compounds with proven in vitro
      antifibrogenic effects on rat pancreatic fibroblasts. We aimed at investigating
      the effects of tocotrienols on human intestinal fibroblast (HIF) proliferation,
      apoptosis, autophagy, and synthesis of ECM. METHODS: HIF isolated from CD,
      ulcerative colitis (UC), and normal intestine were treated with tocotrienol-rich
      fraction (TRF) from palm oil. HIF proliferation was quantified by (3) H-thymidine
      incorporation, apoptosis was studied by DNA fragmentation, propidium iodide
      staining, caspase activation, and poly(ADP-ribose) polymerase cleavage, autophagy
      was analyzed by quantification of LC3 protein and identification of autophagic
      vesicles by immunofluorescence and production of ECM components was measured by
      Western blot. RESULTS: TRF significantly reduced HIF proliferation and prevented
      basic fibroblast growth factor-induced proliferation in CD and UC, but not
      control HIF. TRF enhanced HIF death by promoting apoptosis and autophagy. HIF
      apoptosis, but not autophagy, was prevented by the pan-caspase inhibitor zVAD
      fmk, whereas both types of cell death were prevented when the mitochondrial
      permeability transition pore was blocked by cyclosporin A, demonstrating a key
      role of the mitochondria in these processes. TRF diminished procollagen type I
      and laminin gamma-1 production by HIF. CONCLUSIONS: Tocotrienols exert multiple
      effects on HIF, reducing cell proliferation, enhancing programmed cell death
      through apoptosis and autophagy, and decreasing ECM production. Considering their
      in vitro antifibrogenic properties, tocotrienols could be useful to treat or
      prevent bowel fibrosis in CD patients.

PMID- 20684018
TI  - Fear of anxiety as a partial mediator of the relation between trauma severity and
      PTSD symptoms.
AB  - Fear of anxiety has previously been found to be a predictor of overall symptoms
      of posttraumatic stress disorder (PTSD). The current exploratory study examines
      the relationship between fear of anxiety and symptoms of PTSD in a sample of
      adults exposed to Hurricane Katrina. Fear of anxiety was found to partially
      mediate the relationship between the severity of trauma and the severity of PTSD.
      Further, this mediation was found to operate differently by gender, with the
      mediation holding true for men but not for women. For both men and women, fear of
      anxiety was positively correlated with PTSD symptoms.

PMID- 20684019
TI  - Narrative exposure therapy for 7- to 16-year-olds: a randomized controlled trial
      with traumatized refugee children.
AB  - The authors examined the effectiveness of narrative exposure therapy for children
      (KIDNET) in treating posttraumatic stress disorder (PTSD) in refugee children
      living in exile. Twenty-six children traumatized by organized violence were
      randomly assigned to KIDNET or to a waiting list. Significant treatment by time
      interactions on all PTSD-relevant variables indicated that the KIDNET group, but
      not the controls, showed a clinically significant improvement in symptoms and
      functioning. Success of the KIDNET group remained stable at 12-month follow-up.
      This study confirms previous findings that, if left untreated, PTSD in children
      may persist for an extended period. However, it also shows that it is possible to
      effectively treat chronic PTSD and restore functioning in traumatized refugee
      children in only 8 treatment sessions.

PMID- 20684020
TI  - Acute liver failure is associated with elevated liver stiffness and hepatic
      stellate cell activation.
AB  - Acute liver failure (ALF) is associated with massive short-term cell death,
      whereas chronic liver injury is accompanied by continuous cell death. Hepatic
      stellate cells (HSCs) contribute to tissue repair and liver fibrosis in chronic
      liver injury, although their role in ALF remains unexplained. Twenty-nine
      patients (median age = 43 years, 17 females and 12 males) with ALF according to
      the Acute Liver Failure Study Group criteria were included. Upon the diagnosis of
      ALF and after 7 days, we determined liver stiffness (LS) with FibroScan, standard
      laboratory parameters, and serum levels of matrix metalloproteinase 1 (MMP-1),
      MMP-2, MMP-9, tissue inhibitor of metalloproteinases 1 (TIMP-1), TIMP-2,
      hyaluronic acid, and markers of overall cell death (M65) and apoptosis (M30).
      Stellate cell activation and progenitor response were analyzed
      immunohistochemically in biopsy samples of 12 patients with alpha-smooth muscle
      actin (alpha-SMA), keratin-17, and keratin-19 staining, respectively. Cell death
      markers (M30 level = 2243 +/- 559.6 U/L, M65 level = 3732 +/- 839.9 U/L) and
      fibrosis markers (TIMP-1 level = 629.9 +/- 69.4 U/mL, MMP-2 level = 264 +/- 32.5
      U/mL, hyaluronic acid level = 438.5 +/- 69.3 microg/mL) were significantly
      increased in patients versus healthy controls. This was paralleled by collagen
      deposition, elevated alpha-SMA expression, and higher LS (25.6 +/- 3.0 kPa). ALF
      was associated with ductular progenitor proliferation. CONCLUSION: Our results
      demonstrate HSC activation and a progenitor response in ALF. Positive
      correlations between LS, the degree of liver cell damage, and the intensity of
      HSC activation suggest that fibrosis is a response to ALF in an attempt to repair
      damaged tissue.

PMID- 20684021
TI  - The association of genetic variability in patatin-like phospholipase domain
      containing protein 3 (PNPLA3) with histological severity of nonalcoholic fatty
      liver disease.
AB  - Genome-wide association studies identified single-nucleotide polymorphisms (SNPs)
      that are associated with increased hepatic fat or elevated liver enzymes,
      presumably reflecting nonalcoholic fatty liver disease (NAFLD). To investigate
      whether these SNPs are associated with histological severity of NAFLD, 1117 (894
      adults/223 children) individuals enrolled in the Nonalcoholic Steatohepatitis
      (NASH) Clinical Research Network and National Institutes of Health Clinical
      Center studies with histologically confirmed NAFLD were genotyped for six SNPs
      that are associated with hepatic fat or liver enzymes in genome-wide association
      studies. In adults, three SNPs on chromosome 22 showed associations with
      histological parameters of NASH. After adjustment for age, sex, diabetes, and
      alcohol consumption, the minor allele of rs738409 C/G, a nonsynonymous coding SNP
      in the patatin-like phospholipase domain-containing protein 3 (PNPLA3)
      (adiponutrin) gene encoding an Ile148Met change, was associated with steatosis (P
      = 0.03), portal inflammation (P = 2.5 x 10(-4)), lobular inflammation (P =
      0.005), Mallory-Denk bodies (P = 0.015), NAFLD activity score (NAS, P = 0.004),
      and fibrosis (P = 7.7 x 10(-6)). Two other SNPs in the same region demonstrated
      similar associations. Three SNPs on chromosome 10 near the CHUK (conserved helix
      loop-helix ubiquitous kinase) gene were independently associated with fibrosis (P
      = 0.010). In children, no SNP was associated with histological severity. However,
      the rs738409 G allele was associated with younger age at the time of biopsy in
      multivariate analysis (P = 0.045). CONCLUSION: In this large cohort of
      histologically proven NAFLD, we confirm the association of the rs738409 G allele
      with steatosis and describe its association with histological severity. In
      pediatric patients, the high-risk rs738409 G allele is associated with an earlier
      presentation of disease. We also describe a hitherto unknown association between
      SNPs at a chromosome 10 locus and the severity of NASH fibrosis.

PMID- 20684022
TI  - Loss of skeletal mineralization by the simultaneous ablation of PHOSPHO1 and
      alkaline phosphatase function: a unified model of the mechanisms of initiation of
      skeletal calcification.
AB  - Endochondral ossification is a carefully orchestrated process mediated by
      promoters and inhibitors of mineralization. Phosphatases are implicated, but
      their identities and functions remain unclear. Alkaline phosphatase (TNAP) plays
      a crucial role promoting mineralization of the extracellular matrix by
      restricting the concentration of the calcification inhibitor inorganic
      pyrophosphate (PP(i)). Mutations in the TNAP gene cause hypophosphatasia, a
      heritable form of rickets and osteomalacia. Here we show that PHOSPHO1, a
      phosphatase with specificity for phosphoethanolamine and phosphocholine, plays a
      functional role in the initiation of calcification and that ablation of PHOSPHO1
      and TNAP function prevents skeletal mineralization. Phospho1(-/-) mice display
      growth plate abnormalities, spontaneous fractures, bowed long bones,
      osteomalacia, and scoliosis in early life. Primary cultures of Phospho1(-/-)
      tibial growth plate chondrocytes and chondrocyte-derived matrix vesicles (MVs)
      show reduced mineralizing ability, and plasma samples from Phospho1(-/-) mice
      show reduced levels of TNAP and elevated plasma PP(i) concentrations. However,
      transgenic overexpression of TNAP does not correct the bone phenotype in
      Phospho1(-/-) mice despite normalization of their plasma PP(i) levels. In
      contrast, double ablation of PHOSPHO1 and TNAP function leads to the complete
      absence of skeletal mineralization and perinatal lethality. We conclude that
      PHOSPHO1 has a nonredundant functional role during endochondral ossification, and
      based on these data and a review of the current literature, we propose an
      inclusive model of skeletal calcification that involves intravesicular PHOSPHO1
      function and P(i) influx into MVs in the initiation of mineralization and the
      functions of TNAP, nucleotide pyrophosphatase phosphodiesterase-1, and collagen
      in the extravesicular progression of mineralization.

PMID- 20684023
TI  - Structure of the micronemal protein 2 A/I domain from Toxoplasma gondii.
AB  - Toxoplasma gondii is a widespread zoonotic pathogen capable of causing serious
      disease in humans and animals. As an obligate intracellular parasite, T. gondii
      relies on the orchestrated secretion of proteins from its apical complex
      organelles including the multimodular, transmembrane micronemal protein 2 (MIC2)
      that couples recognition of the host cell with cytoskeletal reorganization of the
      parasite to drive invasion. To probe the basis by which the von Willebrand Factor
      A (vWA)-Integrin like module of TgMIC2 engages the host cell, we solved the
      crystal structure of a truncated form of TgMIC2A/I (TgMIC2A/Ic) phased by iodide
      SIRAS and refined to a resolution of 2.05 A. The TgMIC2A/Ic core is organized
      into a central twisted beta sheet flanked by alpha-helices consistent with a
      canonical vWA fold. A restricted basic patch serves as the putative heparin
      binding site, but no heparin binding was detected in native gel shift assays.
      Furthermore, no metal was observed in the metal ion dependent adhesion site
      (MIDAS). Structural overlays with homologous A/I domains reveal a divergent
      organization of the MIDAS beta4-alpha4 loop in TgMIC2A/Ic, which is stabilized
      through the burial of Phe195 into a deep pocket formed by Gly185. Intriguingly,
      Gly185 appears to be unique among A/I domains to TgMIC2A/I suggesting that the
      divergent loop conformation may also be unique to TgMIC2A/I. Although lacking the
      C-terminal extension, the TgMIC2A/Ic structure reported here is the first of an
      A/I domain from an apicomplexan parasite and provides valuable insight into
      defining the molecular recognition of host cells by these widespread pathogens.

PMID- 20684024
TI  - A new role for OPG: putting RANKL in its place.

PMID- 20684030
TI  - Numerical assessment on the effective mechanical stimuli for matrix-associated
      metabolism in chondrocyte-seeded constructs.
AB  - The self-regeneration capacity of articular cartilage is limited, due to its
      avascular and aneural nature. Loaded explants and cell cultures demonstrated that
      chondrocyte metabolism can be regulated via physiologic loading. However, the
      explicit ranges of mechanical stimuli that correspond to favourable metabolic
      response associated with extracellular matrix (ECM) synthesis are
      elusive.Unsystematic protocols lacking this knowledge produce inconsistent
      results. This study aims to determine the intrinsic ranges of physical stimuli
      that increase ECM synthesis and simultaneously inhibit nitric oxide (NO)
      production in chondrocyte-agarose constructs, by numerically reevaluating the
      experiments performed by Tsuang et al. (2008). Twelve loading patterns were
      simulated with poro-elastic finite element models in ABAQUS. Pressure on solid
      matrix, von Mises stress, maximum principle stress and pore pressure were
      selected as intrinsic mechanical stimuli.Their development rates and magnitudes
      at the steady state of cyclic loading were calculated with MATLAB at the
      construct level. Concurrent increase in glycosaminoglycan and collagen was
      observed at 2300 Pa pressure and 40 Pa/s pressure rate. Between 0-1500 Pa and 0
      40 Pa/s, NO production was consistently positive with respect to controls,
      whereas ECM synthesis was negative in the same range. A linear correlation was
      found between pressure rate and NO production (R =0.77). Stress states identified
      in this study are generic and could be used to develop predictive algorithms for
      matrix production in agarose-chondrocyte constructs of arbitrary shape, size and
      agarose concentration. They could also be helpful to increase the efficacy of
      loading protocols for avascular tissue engineering.

PMID- 20684029
TI  - WISP-1/CCN4 regulates osteogenesis by enhancing BMP-2 activity.
AB  - Wnt-induced secreted protein 1 (WISP-1/CCN4) is a member of the CCN family that
      is highly expressed in skeletal tissue and in osteoprogenitor cells induced to
      differentiate in vitro. To determine the function of WISP-1 during osteogeneis,
      osteogenic bone marrow stromal cells (BMSCs) were transduced with WISP-1
      adenovirus (adWISP-1) in the presence or absence of bone morphogenetic protein 2
      (BMP-2) adenovirus (adBMP-2). WISP-1 overexpression enhanced the ability of BMP-2
      to direct BMSCs toward osteogenic differentiation and appeared to work by
      stimulating Smad-1/5/8 phosphorylation and activation. The ability of WISP-1 to
      enhance BMP-2 activity also was shown in vivo using an ectopic osteogenesis assay
      with BMSCs transduced with WISP-1, BMP-2, or both. When BMSCs were infected with
      lentivirus containing human WISP1 shRNA, they formed less bone in vivo and were
      less responsive to BMP-2, confirming that WISP-1 and BMP-2 have a functional
      interaction. Immunoprecipitation (IP) and Western blot analysis showed that WISP
      1 bound directly to BMP-2 and showed that WISP-1 increased BMP-2 binding to
      hBMSCs in a dose-dependent fashion. To understand how WISP-1 enhanced BMP-2
      signaling, the influence of WISP-1 on integrin expression was analyzed. WISP-1
      induced the mRNA and protein levels of alpha(5)-integrin and, further, was found
      to bind to it. Antibody-blocking experiments showed that the BMP-2 binding to
      BMSCs that was enhanced by WISP-1 was completely neutralized by treatment with
      anti-integrin alpha(5)beta(1) antibody. Pilot studies and the use of transgenic
      mice that overexpressed human WISP-1 in preosteoblasts had increased bone mineral
      density (BMD), trabecular thickness, and bone volume (BV/TV) over wild-type
      controls, supporting observations using human osteoprogenitors that WISP-1 has a
      positive influence on osteogenesis in vivo. In conclusion, these studies show,
      for the first time, that WISP-1 has a positive influence on bone cell
      differentiation and function and may work by enhancing the effects of BMP-2 to
      increase osteogenesis through a mechanism potentially involving binding to
      integrin alpha(5)beta(1).

PMID- 20684031
TI  - Specific attentional impairments and complex visual hallucinations in eye
      disease.
AB  - OBJECTIVE: To test the prediction by the Perception and Attention Deficit (PAD)
      model of complex visual hallucinations that cognitive impairment, specifically in
      visual attention, is a key risk factor for complex hallucinations in eye disease.
      METHODS: Two studies of elderly patients with acquired eye disease investigated
      the relationship between complex visual hallucinations (CVH) and impairments in
      general cognition and verbal attention (Study 1) and between CVH, selective
      visual attention and visual object perception (Study 2). The North East Visual
      Hallucinations Inventory was used to classify CVH. RESULTS: In Study 1, there was
      no relationship between CVH (n=10/39) and performance on cognitive screening or
      verbal attention tasks. In Study 2, participants with CVH (n=11/31) showed poorer
      performance on a modified Stroop task (p<0.05), a novel imagery-based attentional
      task (p<0.05) and picture (p<0.05) but not silhouette naming (p=0.13) tasks.
      Performance on these tasks correctly classified 83% of the participants as
      hallucinators or non-hallucinators. CONCLUSIONS: The results suggest that,
      consistent with the PAD model, complex visual hallucinations in people with
      acquired eye disease are associated with visual attention impairment.

PMID- 20684034
TI  - Crisp: the center for research on interface structures and phenomena, Yale
      University.

PMID- 20684035
TI  - Patterns in nursing home medication errors: disproportionality analysis as a
      novel method to identify quality improvement opportunities.
AB  - PURPOSE: To explore the use of disproportionality analysis of medication error
      data as a novel method to identify relationships that might not be obvious
      through traditional analyses. This approach can supplement descriptive data and
      target quality improvement efforts. METHODS: Data came from the Medication Error
      Quality Initiative (MEQI) individual event reporting system. Participants were
      North Carolina nursing homes who submitted incident reports to the Web-based MEQI
      data repository during the 2006 and 2007 reporting years. Data from 206 nursing
      homes were summarized descriptively and then disproportionality analysis was
      applied. Associations between medication type and possible causes at the state
      level were explored. A single nursing home was selected to illustrate how the
      method might inform quality improvement at the facility level. Disproportionality
      analysis of drug errors in this home was compared with benchmarking. RESULTS:
      Statewide, 59 drug-cause pairs met the disproportionality signal and 11 occurred
      in 10 or more reports. Among these, warfarin was co-reported with communication
      errors; esomeprazole, risperidone, and nitrofurantoin were disproportionately
      associated with transcription error; and oxycodone and morphine were
      disproportionately reported with name confusion. Facility-level analyses
      illustrate how descriptive frequencies and disproportionality analysis are
      complementary, but also identify different safety targets. CONCLUSIONS:
      Exploratory analysis tools can help identify medication error types that occur at
      disproportionate rates. Candidate associations might be used to target patient
      safety work, although further evaluation is needed to determine the value of this
      information.

PMID- 20684036
TI  - Issue dedicated to the memory of Deborah L. Rhatigan.

PMID- 20684037
TI  - Gedenkschrift Honoring Mitchell Rosenthal.

PMID- 20684038
TI  - Special Section: Developmental determinants of sensitivity and resistance to
      stress: A tribute to Seymour 'Gig' Levine.

PMID- 20684039
TI  - Special issue in honor of professor Armen Galoyan.

PMID- 20684040
TI  - [Post-transfusion hemolytic reactions in regions endemic for the hereditary
      glucose-6-phosphate dehydrogenase deficiency].
AB  - This paper deals with the problem of hemocomponent therapy in the use of blood
      components from donors with hereditary glucose-6-phosphate dehydrogenase (G-6-PD)
      deficiency and with the matters of family donation in this blood anomaly.
      Posttransfusion hemolytic reactions during transfusions of packed red blood cells
      from donors with hereditary blood anomaly are retrospectively analyzed.
      Recommendations are formulated for recipients who have undergone transfusions of
      blood components from donors with G-6-PD deficiency.

PMID- 20684041
TI  - Interaction of ibogaine with human alpha3beta4-nicotinic acetylcholine receptors
      in different conformational states.
AB  - The interaction of ibogaine and phencyclidine (PCP) with human (h) alpha3beta4
      nicotinic acetylcholine receptors (AChRs) in different conformational states was
      determined by functional and structural approaches including, radioligand binding
      assays, Ca2+ influx detections, and thermodynamic and kinetics measurements. The
      results established that (a) ibogaine inhibits (+/-)-epibatidine-induced Ca2+
      influx in h(alpha)3beta4 AChRs with approximately 9-fold higher potency than that
      for PCP, (b) [3H]ibogaine binds to a single site in the h(alpha)3beta4 AChR ion
      channel with relatively high affinity (Kd = 0.46 +/- 0.06 microM), and ibogaine
      inhibits [3H]ibogaine binding to the desensitized h(alpha)3beta4 AChR with
      slightly higher affinity compared to the resting AChR. This is explained by a
      slower dissociation rate from the desensitized ion channel compared to the
      resting ion channel, and (c) PCP inhibits [3H]ibogaine binding to the
      h(alpha)3beta4 AChR, suggesting overlapping sites. The experimental results
      correlate with the docking simulations suggesting that ibogaine and PCP interact
      with a binding domain located between the serine (position 6') and
      valine/phenylalanine (position 13') rings. This interaction is mediated mainly by
      van der Waals contacts, which is in agreement with the observed enthalpic
      contribution determined by non-linear chromatography. However, the calculated
      entropic contribution also indicates local conformational changes. Collectively
      our data suggest that ibogaine and PCP bind to overlapping sites located between
      the serine and valine/phenylalanine rings, to finally block the AChR ion channel,
      and in the case of ibogaine, to probably maintain the AChR in the desensitized
      state for longer time.

PMID- 20684042
TI  - Retraction notice to "Prognostic factors for the long-term survival in patients
      with vasospastic angina--Analysis of effects of patients' characteristics and
      therapeutic drugs" [J Cardiol 54 (2009) 10-20].

PMID- 20684043
TI  - Inhibition of cytokine-induced connexin43 hemichannel activity in astrocytes is
      neuroprotective.
AB  - Astrocytes express high levels of connexin43, a protein that forms two types of
      channels: gap junction channels for direct intercellular communication, and
      hemichannels for exchanges with the extracellular space. Inflammation induces
      connexin43 hemichannel activation, which has been proposed to be involved in
      neuroglial interactions. Here, we investigated the contribution of connexin43 to
      NMDA-induced excitotoxicity in neuron/astrocyte co-cultures, after treatment with
      a pro-inflammatory cytokine mixture, containing TNF-alpha and IL1-beta (Mix),
      that stimulated astroglial connexin43 hemichannel activity. Interestingly, NMDA
      treatment induced a higher amount of neurotoxicity in Mix-treated co-cultures
      than in untreated ones, whereas this extent of neurotoxicity was absent in
      enriched neuron cultures or in co-cultures with connexin43 knock-out astrocytes.
      Furthermore, application of connexin43 hemichannel blockers or a synthetic
      cannabinoid prevented the Mix-induced potentiated NMDA neurotoxicity. Altogether,
      these data demonstrate that inflammation-induced astroglial hemichannel
      activation plays a critical role in neuronal death and suggest a neuroprotective
      role of connexin43 hemichannel blockade.

PMID- 20684045
TI  - Copper generated reactive oxygen leads to formation of lysine-DNA adducts.
AB  - This work describes the addition of a lysine derivative to guanine base in a
      nucleoside, an oligonucleotide, and to a large DNA that occurs via oxidation by
      copper generated reactive oxygen species. Nucleophiles present during oxidation
      leads to the formation of adducts. In this work, 2'-deoxyguanosine is oxidized by
      copper generated reactive oxygen species in the presence of a lysine derivative,
      Nalpha-acetyl-lysine methyl ester. Under these conditions the guanidinohydantoin
      lysine adduct is observed in a relative yield of 27% when compared to other
      guanine oxidation products. MS2 strongly supports that lysine is added to the 5
      position during the formation of guanidinohydantoin-lysine. A fourteen-nucleotide
      DNA duplex was oxidized under similar conditions. Digestion showed formation of
      the same guanidinohydantoin-lysine nucleoside. The reaction was then examined on
      a 392-nucleotide DNA substrate. Oxidation in the presence of the lysine ester
      showed adduct formation as stops in a primer extension assay. Adducts
      predominately formed at a 5'-GGG at position 415. Six of the seven sites that
      showed reaction greater than 3-fold above background were guanine sites. We
      conclude from this study that copper can catalyze the formation of DNA-protein
      adducts and may form in cells with elevated copper and oxidative stress.

PMID- 20684044
TI  - Mutually-induced conformational switching of RNA and coat protein underpins
      efficient assembly of a viral capsid.
AB  - Single-stranded RNA viruses package their genomes into capsids enclosing fixed
      volumes. We assayed the ability of bacteriophage MS2 coat protein to package
      large, defined fragments of its genomic, single-stranded RNA. We show that the
      efficiency of packaging into a T=3 capsid in vitro is inversely proportional to
      RNA length, implying that there is a free-energy barrier to be overcome during
      assembly. All the RNAs examined have greater solution persistence lengths than
      the internal diameter of the capsid into which they become packaged, suggesting
      that protein-mediated RNA compaction must occur during assembly. Binding ethidium
      bromide to one of these RNA fragments, which would be expected to reduce its
      flexibility, severely inhibited packaging, consistent with this idea. Cryo-EM
      structures of the capsids assembled in these experiments with the sub-genomic
      RNAs show a layer of RNA density beneath the coat protein shell but lack density
      for the inner RNA shell seen in the wild-type virion. The inner layer is restored
      when full-length virion RNA is used in the assembly reaction, implying that it
      becomes ordered only when the capsid is filled, presumably because of the effects
      of steric and/or electrostatic repulsions. The cryo-EM results explain the length
      dependence of packaging. In addition, they show that for the sub-genomic
      fragments the strongest ordered RNA density occurs below the coat protein dimers
      forming the icosahedral 5-fold axes of the capsid. There is little such density
      beneath the proteins at the 2-fold axes, consistent with our model in which coat
      protein dimers binding to RNA stem-loops located at sites throughout the genome
      leads to switching of their preferred conformations, thus regulating the
      placement of the quasi-conformers needed to build the T=3 capsid. The data are
      consistent with mutual chaperoning of both RNA and coat protein conformations,
      partially explaining the ability of such viruses to assemble so rapidly and
      accurately.

PMID- 20684046
TI  - Evidence supporting a biological role for aluminum in chromatin  compaction  and
      epigenetics.
AB  - Averaging 8.1% (w/w) of the earth's crust, aluminum is the most highly abundant
      metal in our biosphere, yet has long been thought to serve no essential
      biological function. In aqueous solutions, aluminum salts and hydroxides are
      exceptionally potent aggregators of biological molecules, often coalescing
      molecular species to the point that they precipitate out of solution. A
      biological function for aluminum is proposed in which this abundant, high charge
      density metal cation has a significant role in biomolecular compaction.
      Sometimes, molecules ectopically aggregated by aluminum are associated with
      pathological conditions. The data further suggests that a specific consequence of
      'aluminum biocompaction' may be particularly important in the condensation of A+T
      rich chromatin domains, and in silencing the expression of specific kinds of
      genetic information.

PMID- 20684047
TI  - Guest editorial. Special section on affective and pervasive computing for
      healthcare.
AB  - This special section is focused on the novel and practical ways, and solid
      contributions, to improve affective computing and pervasive technologies. There
      are 19 papers in this special section.

PMID- 20684048
TI  - Guest editorial. Special section on personal health systems.
AB  - This special section on personal health systems (PHSs) features 13 papers in
      three main areas: new-micro-nano instrumentation, sensors, and sensor-based
      systems; new information processing technology via embedding intelligence in PHS;
      and PHS platforms to address specific clinical applications.

PMID- 20684049
TI  - Editorial note on Bio, medical, and health informatics.

PMID- 20684050
TI  - Guest editorial special section on new and emerging technologies in
      bioinformatics and bioengineering.

PMID- 20684052
TI  - Current issues in neuroimaging.

PMID- 20684051
TI  - Guest editorial special section on smart wearable devices for human health and
      protection.

PMID- 20684053
TI  - Otosclerosis: disturbed balance between cell survival and apoptosis.
AB  - HYPOTHESIS: Otosclerosis is an inflammatory bone remodeling disorder of the human
      otic capsule, which might be characterized by a disturbed balance between cell
      survival and apoptosis due to an increased expression of inflammatory cytokines,
      mainly tumor necrosis factor-[alpha] (TNF-[alpha]). BACKGROUND: Histologic
      features of otosclerosis have been well described; however, different
      histopathologic and clinical stages have not been attributed precisely to the
      molecular biology of the pathologically increased metabolism of bone-forming and
      bone-resorbing cells. METHODS: Forty ankylotic stapes footplates (n = 40, males =
      17, females = 23) removed by stapedectomy were histologically analyzed by
      conventional hematoxylin-eosin staining, and hCIAP1/2 (inhibitors of apoptosis)
      and granzyme-[beta] (apoptosis inducer) specific immunofluorescent assays were
      performed. Four normal stapes footplates obtained from cadavers with negative
      otologic history were used as negative controls. RESULTS: Active otosclerosis (n
      = 19) was featured by robust expression of apoptosis inhibitor proteins hCIAP1/2
      and negligible expression of granzyme-[beta]. Inactive cases of otosclerosis (n =
      8) were characterized by inverse reaction: granzyme-[beta] was highly expressed;
      however, hCIAP1/2 specific immunoreactions were absent. Nonotosclerotic and
      normal stapes specimens showed no considerable little granzyme-[beta] expression
      and moderate hCIAP1/2-specific immunoreactions. Expression pattern of apoptosis
      associated proteins showed strong correlation with the histologic diagnosis and
      activity of otosclerosis (Yates-corrected [chi]2 test, p < 0.001). CONCLUSION:
      Detection of the inversely expressed apoptosis inhibitor and inducer proteins in
      active and inactive stages of otosclerosis demonstrates pathologic regulation of
      cell survival and apoptosis. These results may suggest active otosclerosis
      inactivation by TNF-[alpha] induced apoptosis. Anti-TNF-[alpha] biologics may
      serve as an option in the medical treatment of active otosclerosis.

PMID- 20684054
TI  - Optical coherence tomography of cholesteatoma.
AB  - OBJECTIVES: To image cholesteatoma using optical coherence tomography (OCT) and
      correlate the results with clinical findings and conventional observations
      obtained using binocular microscopy and histology. OCT is a high-resolution
      optical imaging modality that generates cross-sectional images of turbid media,
      such as tissue with resolution approaching that of light microscopy. OCT relies
      on intrinsic differences in tissue optical properties for image contrast. STUDY
      DESIGN: In vivo prospective clinical study. SETTING: University Medical Center.
      PATIENTS: Patients with cholesteatoma undergoing otologic surgery. INTERVENTION:
      Using a commercial OCT imaging system, we obtained cross-sectional images
      (resolution, approximately 10 microm; depth penetration, approximately 1 mm) of
      cholesteatomas. MAIN OUTCOME MEASURES: Images are obtained by raster scanning a
      single mode fiber across the interior of the probe. The imaging probe is
      sterilized and inserted into the middle ear or mastoid under microscopic
      guidance, and still images of the middle ear or mastoid mucosa and cholesteatoma
      when present were obtained. RESULTS: OCT images of cholesteatomas demonstrate
      differences in signal intensity, which are distinct from those of normal or
      inflamed middle ear/mastoid mucosa. Identification of keratin in cholesteatoma,
      even if very thin, distinguished it from inflamed mucosa. CONCLUSION: This is the
      first study that systematically used OCT to image cholesteatoma during otologic
      surgery. Cholesteatomas can be distinguished from normal or inflamed adjacent
      mucosa.

PMID- 20684055
TI  - Long-term results of palisade cartilage tympanoplasty.
AB  - OBJECTIVE: Evaluation of morphologic and functional long-term results of palisade
      cartilage tympanoplasty (PCT) combined with titanium ossicular replacement
      prostheses. STUDY DESIGN: Retrospective review of tympanoplasties. SETTING:
      Tertiary referral center. PATIENTS: Twenty-nine patients (12 women and 17 men;
      mean age, 39 yr; range, 17-72 yr) operated on more than 9 years ago (mean follow
      up, 9.1 yr) because of cholesteatoma, adhesive otitis, chronic otitis media,
      subtotal tympanic membrane defects, and tympanic fibrosis requiring
      tympanoplasty. INTERVENTIONS: Tympanoplasty, applying the PCT. For
      ossiculoplasty, total or partial titanium ossicular replacement prostheses were
      used. MAIN OUTCOME MEASURES: Questionnaire on postoperative course, otoscopic
      findings, and hearing results using a 4-frequency pure-tone average air-bone gap.
      RESULTS: A recurrent defect was not observed. The graft take rate was 100%. There
      was one case of prosthesis protrusion which required revision surgery and
      insertion of a shorter prosthesis. A pure-tone average air-bone gap of 0 to 10 dB
      was seen preoperatively in 1 ear, 11 to 30 dB in 16 ears, and 31 to 59 dB in 12
      ears. Postoperatively, the corresponding numbers were 10, 15, and 4 ears.
      CONCLUSION: The PCT is a reliable surgical method to manage difficult middle ear
      pathology on a long-term (>9 yr) basis. It offers satisfactory morphologic and
      functional results in combination with titanium prosthesis ossiculoplasty.

PMID- 20684056
TI  - New considerations in the cause of spontaneous cerebrospinal fluid otorrhea.
AB  - OBJECTIVE: To examine the demographic and radiographic features of patients with
      spontaneous cerebrospinal fluid otorrhea and to determine whether they display
      similar characteristics to patients with idiopathic intracranial hypertension.
      STUDY DESIGN: Retrospective case review. SETTING: Academic, tertiary referral
      center. PATIENTS: All individuals presenting with spontaneous cerebrospinal fluid
      otorrhea, diagnosed between 2000 and 2009, undergoing primary surgical repair.
      INTERVENTIONS: All patients underwent surgical repair via a transmastoid, middle
      fossa, or combined transmastoid-middle fossa approach. MAIN OUTCOME MEASURES:
      Patient demographics such as age, race, sex, height, weight, and body mass index,
      the presence of a radiographically empty or partially empty sella, and
      preoperative radiographic and intraoperative surgical findings of the temporal
      bone. RESULTS: Twenty-three patients underwent primary surgical repair for
      spontaneous cerebrospinal fluid otorrhea. Fifteen patients underwent preoperative
      magnetic resonance imaging of the head with 12 (80%) demonstrating the presence
      of an empty or partially empty sella. Mean body mass index of those patients with
      an empty or partially empty sella was 38.0 kg/m2 compared with 28.5 kg/m2 for
      those without an empty sella. CONCLUSION: Patients with spontaneous cerebrospinal
      fluid otorrhea are often middle-aged and obese, with females being affected
      nearly twice as often as males. Empty or partially empty sella was observed in
      80% of patients with spontaneous cerebrospinal fluid otorrhea as demonstrated by
      preoperative magnetic resonance imaging. Patients with spontaneous cerebrospinal
      fluid otorrhea who display these demographic and radiographic features should be
      further evaluated for the presence of idiopathic intracranial hypertension.

PMID- 20684057
TI  - Factors influencing the knowledge of 'evidence-based medicine' in sixth-year
      medical students.

PMID- 20684058
TI  - Middle ear dimensions in congenital aural atresia and hearing outcomes after
      atresiaplasty.
AB  - OBJECTIVE: To determine if middle ear dimensions in congenital aural atresia
      (CAA) patients can predict early postoperative audiometric outcomes in order to
      establish specific parameters that facilitate stratification of surgical
      candidates. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral
      center. PATIENTS: Twenty-five patients with CAA (28 atretic ears and 22
      nonatretic ears) and 12 controls (24 ears). INTERVENTION: Primary repair of
      congenital aural atresia. MAIN OUTCOME MEASURES: Measure and compare middle ear
      dimensions in controls, atretic ears, and nonatretic ears in unilateral CAA.
      Determine correlations between the dimensions and best speech reception threshold
      during the first postoperative year (SRT-1). RESULTS: The epitympanic depth,
      medial canal diameter, and the mesotympanic height, area, and estimated volume
      measurements in atretic ears differ significantly with those in control ears. The
      mesotympanic length, area, and estimated volume measurements each correlate
      significantly with SRT-1. Atretic ears with a mesotympanic volume estimate
      measurement greater than or equal to 42 mm3 are 24 times more likely to have an
      SRT-1 of 25 dB or better than those measuring less than 42 mm3 (odds ratio =
      24.5; 95% confidence interval, 2.826-212.4; Fisher's exact test, p = 0.0022).
      CONCLUSION: Middle ear measurements in appropriately selected patients may help
      predict successful early hearing outcomes after atresiaplasty, thus offering a
      valuable tool for the surgical decision-making process.

PMID- 20684059
TI  - Webinar: free international distant real time interactive tutoring.

PMID- 20684060
TI  - Parents as practitioners in pediatrics.

PMID- 20684061
TI  - Vestibular evoked myogenic potentials and health-related quality of life in
      patients with vestibular neuritis.
AB  - OBJECTIVE: To evaluate the usefulness of vestibular evoked myogenic potentials
      (VEMPs) in subjects with vestibular neuritis (VN) and to determine the impact of
      the disease in health-related quality of life (HRQoL). STUDY DESIGN: Case series.
      SETTING: Tertiary referral center. PATIENTS: Fifty patients with VN (episode of
      sudden onset of prolonged vertigo [>24 h] associated with peripheral vestibular
      hypofunction, imbalance in absence of hearing loss, or other neurologic
      symptoms). INTERVENTION: VEMPs were measured in 41 patients by using an air
      conducted 500 Hz tone burst. HRQoL was evaluated in all cases by the Medical
      Outcomes Study 36-Item Short Form Health Survey (SF-36) and Dizziness Handicap
      Inventory Short Form (DHI-S) instruments, after the acute episode was resolved.
      MAIN OUTCOME MEASURE: Latencies P1 or N1 peaks, corrected amplitude or the
      absence of response, for VEMPs; scores obtained in SF-36 and DHI-S instruments.
      RESULTS: VEMPs showed abnormal results in 21 (51%) of 41 cases, with an increase
      in ipsilateral latencies for P1 and N1 peaks being the most common finding. Three
      patients (7%) had ipsilateral abnormal VEMP response with normal caloric
      response, indicating isolated involvement of inferior vestibular nerve. The total
      score obtained for the DHI-S was 14.76 +/- 11.07 (range, 0-34/40), suggesting a
      variable impact among patients with VN. For the SF-36, scores in men with VN were
      worse than their age-matched controls for all dimensions, except for mental
      health. However, women only showed lower scores for general health and social
      function. CONCLUSION: Abnormal VEMP responses demonstrate the involvement of the
      inferior vestibular nerve in half of the patients with VN. Moreover, VN has a
      moderate impact in HRQoL, and it is perceived more disabling by men than women.

PMID- 20684062
TI  - Copper toxicity in gibel carp Carassius auratus gibelio: importance of sodium and
      glycogen.
AB  - In general, copper is primarily an osmoregulatory toxicant to fish and Cu
      toxicity is thought to be related to the rate of sodium loss. Looking at a
      previous research it is striking that gibel carp, Carassius auratus gibelio, do
      not seem so susceptible to the first ionoregulatory shock phase of Cu exposure,
      but rather build up physiological disturbances slowly until mortality occurs.
      Since it was noted that gibel carp experience severe hypoxia under Cu exposure,
      we hypothesised that, besides the Na loss, the slow depletion of liver glycogen
      stores contributed equally to the collapse of physiological integrity. It is
      clear from our results that glycogen stores are being depleted in Cu exposed fish
      and that dead fish suffered more extensive glycogen losses compared to surviving
      fish, with liver glycogen levels of 125+/-8 mg g(-1) in dead fish compared to
      230+/-13 mg g(-1) in surviving fish. However, changes in liver glycogen did not
      contribute significantly to mortality, while changes in whole body sodium and the
      rate of sodium loss did. Whole body Na levels dropped from 1111+/-48 microg g(-1)
      dry weight in control fish to 850+/-54 microg g(-1) in surviving fish and to
      607+/-24 microg g(-1) in fish that had died resulting in Na loss rates of 1.25+/
      0.22 microg g(-1) h(-1) and 3.39+/-0.19 microg g(-1) h(-1) in surviving and dead
      fish respectively. Our results support the finding that the rate of Na loss
      largely determines Cu toxicity in fish, even in resistant species.

PMID- 20684063
TI  - Audiovestibular factors influencing quality of life in patients with
      conservatively managed sporadic vestibular schwannoma.
AB  - OBJECTIVES: To measure the health-related quality of life (QoL) of patients
      undergoing conservative management of a vestibular schwannoma and to identify
      audiovestibular factors that influence health-related QoL. STUDY DESIGN: Cross
      sectional case-control study. INTERVENTION: Adult patients undergoing
      conservative management of a sporadic vestibular schwannoma were identified from
      a prospectively updated database. Each patient was asked to complete a series of
      questionnaires, including the Short Form 36 health-related QoL instrument, the
      Hearing Handicap Inventory, the Tinnitus Handicap Inventory, and the Dizziness
      Handicap Inventory. The QoL data obtained were compared with UK normal data.
      Multiple linear regression was performed to identify audiovestibular factors
      influencing QoL. PATIENTS: Of 241 patients still undergoing conservative
      management, 165 completed the questionnaires. The mean age was 66.6 years. Mean
      duration of follow-up was 5.7 years. RESULTS: Physical component summary scores
      were significantly lower than those of the normal population. Mental component
      summary scores were significantly above the normal population. Regression
      analysis showed that dizziness handicap score and age were strong predictors of
      physical component summary (both p < 0.0001). Dizziness handicap score and
      tinnitus handicap score were significant predictors of mental component summary
      (p = 0.0004 and p = 0.027 respectively). However, the model only explained a
      small amount of the data, suggesting that there may be other factors influencing
      QoL. CONCLUSION: Dizziness is the most significant audiovestibular predictor of
      QoL in patients with vestibular schwannomas. Tinnitus also has an impact on
      mental QoL. Hearing loss does not seem to influence QoL. Other factors such as
      illness perception may have an important role to play in determining QoL.

PMID- 20684064
TI  - Proceedings of the 1st Ibero-American Meeting on Toxicology and Environmental
      Health (IBAMTOX 2009). Ribeirao Preto, SaoPaulo, Brazil.

PMID- 20684065
TI  - Cochlear hydrops analysis masking procedure results in patients with unilateral
      Meniere's disease.
AB  - OBJECTIVE: To investigate the usefulness of the cochlear hydrops analysis masking
      procedure (CHAMP) as an additional diagnostic test in patients with definite
      unilateral Meniere's disease. STUDY DESIGN: Prospective validation study for a
      diagnostic test. SETTING: Tertiary referral center. PATIENTS: Subjects (n = 22)
      with definite unilateral Meniere's disease. INTERVENTIONS: The CHAMP test was
      performed in both ears of the patients. MAIN OUTCOME MEASURE: Difference in
      latency delay between the affected and the unaffected ears. RESULTS: In 20
      subjects, latency delays could be measured in both ears. The mean latency delay
      for the affected ears (0.55 ms; standard error, 0.12 ms) differs significantly
      from that for the unaffected ears (3.36 ms; standard error, 0.43 ms). With the
      standard criterion to separate ears with an abnormally short delay (<0.3 ms) from
      ears with a normal delay, in only 7 of 20 affected ears, an abnormally short
      delay was measured. All 33 other ears produced a normal delay. With the less than
      0.3 ms criterion and including the ears in which no delay could be measured, the
      sensitivity of the CHAMP is 32% (7/22). Pooling CHAMP latency delays for 235 ears
      from this work and the literature yielded 2 clearly distinct distributions, with
      a separation at 2 ms. Defining abnormal delays as shorter than 2 ms gave an
      abnormal delay for 18 of 20 affected ears and for 7 of 20 unaffected ears.
      CONCLUSION: Abnormal latency delays for CHAMP are delays shorter than 2 ms.
      Earlier results with CHAMP should be reconsidered using this criterion, instead
      of 0.3 ms.

PMID- 20684066
TI  - Current awareness in NMR in biomedicine.

PMID- 20684067
TI  - New developments in pathogenicity and virulence of necrotrophs.
AB  - It was generally considered that necrotrophic plant pathogenic fungi possessed
      simplistic pathogenic mechanisms being typically reliant on 'blasting their way
      through host tissue with a battery of lytic and degradative enzymes. However
      recent studies have suggested that this is not true and that necrotrophic fungal
      pathogens can subtly manipulate the host during infection in a manner similar to
      biotrophic pathogens. For example, it has been demonstrated that the wheat
      pathogens Stagonospora nodorum and Pyrenophora triticirepentis secrete small
      unique proteins (effectors) that are internalised by host cells and interact with
      the host in a gene-for-gene relationship to initiate disease, albeit in an
      inverse manner compared to biotrophs. This paper reviews recent developments in
      necrotrophic fungal pathogenicity throughout a critical period that arguably saw
      this field come of age.

PMID- 20684068
TI  - Effects of corticosterone synthesis inhibitor metyrapone on anxiety-related
      behaviors in Lurcher mutant mice.
AB  - Beyond their motor impairments, the cerebellar Lurcher mutant mice show an
      alteration of the anxiety-related behaviors we called "behavioral disinhibition".
      This is characterized by a low avoidance towards the open arms of the elevated
      plus-maze device paradoxically combined with a dramatic blood corticosterone
      level rise induced by the exposure to the experimental conditions. The present
      study was aimed at determining if the disinhibition of the mutants could be
      caused by their stress-induced high corticosterone rate. For this purpose, we
      compared the behaviors of Lurcher and control mice in the elevated plus-maze test
      after injection of either 2-methyl-1.2-di-3-pyridil-1-propanone (metyrapone; 75
      mg/kg), a corticosterone synthesis inhibitor, or vehicle alone (Tween 80, 5%).
      Our results showed that metyrapone, although efficiently reducing their blood
      corticosterone rate, provoked only modest modifications of the anxiety-related
      behaviors in mice of both genotypes. As a result, the behavioral distance between
      the Lurcher and control mice slightly decreased, without being totally abolished.
      Thus, it seems that the behavioral disinhibition of the mutants is caused only in
      part by their stress-provoked high corticosterone level. As a complementary
      hypothesis, we propose that the behavioral disturbances observed in the Lurcher
      mice also might arise from dysfunctions of the neural pathways connecting the
      cerebellum with some limbic structures known to be highly involved in the
      regulation of emotions.

PMID- 20684069
TI  - Re: A method for securing eyeglasses in position whilst operating.

PMID- 20684070
TI  - Crystal structure of the 2-oxoglutarate- and Fe(II)-dependent lysyl hydroxylase
      JMJD6.
AB  - Lysyl and prolyl hydroxylations are well-known post-translational modifications
      to animal and plant proteins with extracellular roles. More recent work has
      indicated that the hydroxylation of intracellular animal proteins may be common.
      JMJD6 catalyses the iron- and 2-oxoglutarate-dependent hydroxylation of lysyl
      residues in arginine-serine-rich domains of RNA splicing-related proteins. We
      report crystallographic studies on the catalytic domain of JMJD6 in complex with
      Ni(II) substituting for Fe(II). Together with mutational studies, the structural
      data suggest how JMJD6 binds its lysyl residues such that it can catalyse C-5
      hydroxylation rather than Nepsilon-demethylation, as for analogous enzymes.

PMID- 20684071
TI  - Leukocytosis, thrombosis and early mortality in cancer patients initiating
      chemotherapy.
AB  - BACKGROUND: Leukocytosis has been associated with thrombosis and mortality in
      cancer patients. We explored the association of leukocytosis with venous
      thromboembolism (VTE) and early mortality in cancer patients initiating
      chemotherapy. METHODS: Data from a prospective, multicenter observational study
      of treatment-related complications in 4,405 ambulatory cancer patients initiating
      chemotherapy was used for this analysis. The association of leukocytosis, VTE and
      mortality during the course of chemotherapy was evaluated in univariate and
      multivariate analysis. RESULTS: Ninety-three patients (2.1%) developed VTE and
      134 (3%) died over a median follow up of 75 days (range 0-384). Of 4391 patients
      with available baseline white blood cell (WBC) count, 561 (12.8%) had elevated
      pretreatment leukocyte counts, defined as WBC > 11 x 10(9) cells/L. VTE occurred
      in 25 of 561 patients (4.5%) with baseline leukocytosis compared to 68 of 3830
      (1.8%) with WBC <or= 11 x 10(9) cells/L (P < 0.0001). Baseline leukocytosis was
      associated with VTE by multivariate analysis as well (HR 2.1, 95% confidence
      interval 1.3-3.4, p = 0.003). Forty one patients (7.3%) with leukocytosis died
      compared to 92 (2.4%) with WBC <or= 11 x 10(9) cells/L (P < 0.0001). Baseline
      leukocytosis was associated with early mortality by multivariate analysis as well
      (HR 2.2, 95% confidence interval 1.5-3.3, p < 0.0001). Mortality was greatest in
      patients with both leukocytosis and VTE. In multivariate analysis several factors
      were predictive of leukocytosis. CONCLUSIONS: Elevated WBC, particularly
      neutrophils, is strongly associated with increased risk of VTE and mortality in
      cancer patients receiving systemic chemotherapy. Further studies are needed to
      elicit the mechanisms involved.

PMID- 20684072
TI  - Getting help through couples therapy.  Under stress, even loving couples may
      encounter difficulties.  Therapy can help put the relationship back on track.

PMID- 20684073
TI  - Bringing psoriasis under control.  Treatment can improve the quality of life for
      people who have this common disorder.

PMID- 20684074
TI  - Exercise limits weight gain in normal-weight but not heavier women.

PMID- 20684075
TI  - Urine color and odor changes.  Many things can alter the look and smell of your
      urine.  When should you be concerned?

PMID- 20684076
TI  - By the way, doctor. A relative in Australia was told to take krill oil capsules,
      which are advertised as better for heart health than fish oil. What's your
      opinion?

PMID- 20684077
TI  - Too early to get up, too late to get back to sleep. Sleep-maintenance insomnia is
      a common complaint among women at midlife.

PMID- 20684078
TI  - Progress in treating multiple myeloma.  Thanks to a host of effective new
      therapies, patients are enjoying years in remission from this malignant blood
      cancer.

PMID- 20684079
TI  - Study finds no link between bone drugs and unusual thigh fractures.

PMID- 20684080
TI  - Unequal leg length may be a risk for osteoarthritis of the knee.

PMID- 20684081
TI  - By the way, doctor.  Is it true that cataracts are made of calcium?  Can I do
      anything to avoid getting a cataract?  What about diet?

PMID- 20684082
TI  - Expressing the self in Bengali women's autobiographies in the twentieth century.
AB  - This article discusses evidence from the autobiographical writings of three
      Bengali women to explore expressions of the self in such literature. Sarala Devi
      Chaudhurani, Santisudha Ghosh and Manikuntala Sen were contemporaries, all three
      active in different capacities in the various political formations that shaped
      the outcome of the struggle against colonial occupation. Their autobiographies
      lay bare the prescriptions they encountered as daughters and women and the
      choices they made, all the time straddling multiple worlds, occupying multiple
      subject positions. The article contends that these autobiographies, along with
      other personal and public documents, reflect the construction of tortured,
      fractured female subjectivities that must continually negotiate with "modernity"
      in early twentieth century Bengal. Consequently, the "female self" in these
      autobiographies is not a securely rooted and stable entity but is constantly
      "becoming", as the various fragments try to cohere around an elusive centre,
      "modernity", which is itself a nebulous, unstable product of multiple discourses.

PMID- 20684083
TI  - Two accounts of the colonised "other" in South Asia re-exploring alterity.
AB  - Taking examples from South Asia, this article shows how British colonial
      knowledge about the non-European "other" hinged substantially on the
      participation of sections of that other, especially in the context of liminal
      groups, for whom no ready standardised formula of identification was available.
      Development of a colonial episteme often involved active intervention from the
      colonised body, thereby dispelling any strict notion of coloniser-colonised
      alterity and mere top-down governance. This process of identity construction took
      place in several arenas and also involved negotiations in courts of law, where
      rival sections of the amorphous colonised body fought for competing ideals of
      selfhood. Complementing this legal construction were ethnographic formulations,
      internally diverse, and often relating to broader politico-intellectual concerns
      and debates of the Empire, at different planes in different ways. The article
      explicates their theoretical bases and practical modalities.

PMID- 20684084
TI  - "The hard hunger": famine, sexuality, and form in Eugene McCabe's Tales from the
      poorhouse.

PMID- 20684085
TI  - Historical analysis of participation in 161 km ultramarathons in North America.
AB  - Participation trends in 100 m (161 km) ultramarathon running competitions in
      North America were examined from race results from 1977 through 2008. A total of
      32, 352 finishes accounted for by 9815 unique individuals were identified. The
      annual number of races and number of finishes increased exponentially over the
      study period. This growth in number of finishes occurred through a combination of
      (1) an increase in participation among runners >40 years of age from less than
      40% of the finishes prior to the mid-1980s to 65-70% of the finishes since 1996,
      (2) a growth (p < 0.0001) in participation among women from virtually none in the
      late 1970s to nearly 20% since 2004, and (3) an increase in the average annual
      number of races completed by each individual to 1.3. While there has been
      considerable growth in participation, the 161 km ultramarathon continues to
      attract a relatively small number of participants compared with running races of
      shorter distances.

PMID- 20684086
TI  - "Because I was in pain, I just wanted to be treated": competing therapeutic goals
      in the performance of healing HIV/AIDS in rural Zimbabwe.
AB  - Zimbabwe is experiencing one of the most severe AIDS epidemics in the world, with
      an estimated one out of seven people infected with HIV. For both palliative care
      and pragmatic treatment of HIV-related opportunistic infections, people turn to
      Un'anga (the traditional system of health and healing), not as a substitute for
      Western therapeutics but as an alternative explanatory model for the diagnosis
      and management of illness. Through the use of highly charged symbols and
      ritualized communication, n'angas (traditional healers) seek to transform
      patients' understandings and experiences of HIV-related illness. Using
      performance theory and discourse analysis, this article seeks to expand our
      understanding of how competing therapeutic goals in the performance of healing
      affect the structure and content of performance, its subsequent meaning, and the
      therapeutic effect on those afflicted with HIV.

PMID- 20684087
TI  - [Head and neck cancer].

PMID- 20684088
TI  - [Effectiveness of PET/CT for diagnosis of head and neck cancer].

PMID- 20684089
TI  - [Treatment of advanced head and neck cancer by TPF].

PMID- 20684090
TI  - [Effectiveness of concurrent chemoradiation therapy using TPF].

PMID- 20684091
TI  - [Effectiveness and problems of salvage surgery].

PMID- 20684092
TI  - Common fate, different experience: gender-specific aspects of the Armenian
      Genocide, 1915-1917.
AB  - Violence against women was a central feature of the Armenian Genocide. Even
      before the mass killings, sexual humiliation was used to intimidate the Armenian
      community. After the murder of the Armenian leadership and men of military age,
      Ottoman authorities and Ittihadist supporters deported surviving Armenians from
      Anatolia into the Syrian desert. During this ethnic cleansing, rape, kidnapping,
      sex slavery, and forced re-marriage became de facto instruments of genocide.
      Eyewitness accounts and diplomatic reports shed light on the place of gender
      during genocidal persecution. Although scholarship has only recently begun to
      explore the issue, the Armenian Genocide offers opportunities for comparative
      gender studies.

PMID- 20684093
TI  - Extermination of the Gypsies in Estonia during World War II- popular images and
      official policies.
AB  - A discussion of Nazi anti-Gypsy policy in Estonia needs to center on local
      interpretation and implementation of RSHA and RKO orders. Contradictions between
      various German instructions, which often discriminated among sedentary and
      itinerating Gypsies, created a state of confusion that increased chances for
      survival. Since in Estonia Sonderkommando 1a of the German Security Police
      exercised oversight rather than itself carrying out atrocities, the destruction
      of the Gypsy community in Estonia proceeded at a pace slower than elsewhere in
      Eastern Europe. Interested in exploiting slave labor, the German Security Police
      in Estonia did not consider liquidation of the Gypsies a priority. Acculturated
      to traditional anti-Gypsy prejudices and burdened by their own wartime travails,
      the majority of Estonians remained indifferent when Estonian police deported
      Gypsies.

PMID- 20684094
TI  - Who died in the Holocaust? Recovering names from official records.
AB  - The names of most Holocaust victims from Central and East Europe have remained
      unknown, but can be retrieved from official records, as illustrated here for the
      town of Liepaja, Latvia. Drawing on thirteen different sources, the authors have
      recovered the names and fates of about 7,000 of the 7,140 Jews once living there.
      The main source (5,700 names) is a census conducted during August 1941, the
      second month of the German occupation. Other sources are victims' lists compiled
      by Yad Vashem and by the Soviet Extraordinary Commission, house books, police and
      camp records, telephone and business directories, lists of deportees to the USSR,
      survivor reports, etc. All sources are incomplete and many are error-ridden, but
      they usually can be reconciled. Coverage of victims from Liepaja thus has
      increased from 20% to over 95%. For most victims, accurate data are now available
      on birth dates and places, prewar and wartime addresses, occupations, etc.,
      permitting analysis of demography, survival patterns, and other trends.

PMID- 20684095
TI  - "Another type of perpetrator": the SS racial experts and forced population
      movements in the occupied regions.
AB  - The "racial experts" of the Race and Settlement Main Office of the SS (RuSHA)
      were an important, yet not well studied, group of perpetrators. By setting up a
      procedure for "racial examination" that was applied not only to the members of
      the SS but also to millions of civilians in the Occupied Territories, they
      provided the ideological background and logistics of persecution. Following the
      outbreak of war, the racial experts' qualification of persons as "desirable" or
      "undesirable" guided National Socialist population policy and the planned ethnic
      reconstruction of Europe. This article analyzes these SS racial experts' efforts
      to legitimize, implement, and accelerate not only forced population movements in
      general, but also the "Final Solution".

PMID- 20684096
TI  - The Nazi ethnographic research of Georg Leibbrandt and Karl Stumpp in Ukraine,
      and its North American legacy.
AB  - Scholars have recently debated the topic of German academics who directly or
      indirectly served the Nazi machinery of death and who then went on to successful
      professional careers after the war. This article examines the activities of two
      prominent emigre scholars, Drs. Georg Leibbrandt (1899-1982) and Karl Stumpp
      (1896-1982). These Ukrainian Germans emigrated to Germany after World War 1. In
      America, most members of the Russian-German ethnic community never knew that
      Leibbrandt had represented Alfred Rosenberg's Ministry for the Occupied Eastern
      Territories, or that under his supervision Stumpp led a Sonderkommando in
      Ukraine. This unit classified hundreds of villages, indirectly documenting the
      annihilation of Jews and others. The authors conclude that one consequence of
      Leibbrandt's and Stumpp's "return to normalcy" after the war was the growing
      fascination with genealogical research that affected the Russian-German ethnic
      community in North America-research partly based on 1930s and 1940s Nazi racial
      record-keeping.

PMID- 20684097
TI  - Written on the body: narrative re-presentation in Charlotte Delbo's Auschwitz and
      after.
AB  - In "re-membering" the atrocities inflicted on her body and those of her comrades
      in the Nazi concentration camps, the French memoirist Charlotte Delbo avoids the
      linear time scheme and the metaphors for self that have traditionally defined
      autobiography as a genre. Instead, her depiction of time is circular, and the
      depiction of self and other is that of dismembered bodies and fragmented psyches.
      As conditions for the French political prisoners improved late in the war, numbed
      emotions thawed and Delbo's group began to recapture their pre-Auschwitz identity
      by reviving their pre-Auschwitz language. In recording testimonies garnered more
      than twenty years after the war, Delbo demonstrates that although the women were
      forever frozen in the time-space continuum of Auschwitz, they were also bonded
      into something larger than the sum of their once "dismembered selves."

PMID- 20684098
TI  - Gypsies and Jews under the Nazis.
AB  - This article compares the fate of the Gypsies under the Third Reich to that of
      the Jews, arguing that, despite parallels, the treatment each group underwent
      differed fundamentally. The Nazis never formulated a plan for a "Final Solution"
      to the Gypsy problem analogous to that for the Jews. Compulsory sterilization
      affected only a relatively small portion of the Gypsy population, and killings
      that did take place were carried out to achieve Nazi solutions to specific local
      situations. Numerous sources, especially recently discovered local police files,
      show that large numbers of "racially pure" and "socially adjusted" Gypsies were
      exempted from deportation to the Gypsy family camp in Auschwitz and were allowed
      to survive the war.

PMID- 20684099
TI  - Health care in the Vilna ghetto.
AB  - The distinguished medical tradition of Jewish Vilna was maintained during the
      ghetto years, 1941-1943. The large number of physicians and other medical
      personnel in the Vilna ghetto, and the inclusion of the prewar Jewish hospital
      within its boundaries, made possible an effective medical establishment that
      worked closely with the ghetto administration. In addition to the hospital,
      clinic, and other medical institutions, the highly organized Sanitary
      Epidemiological Section oversaw the strict enforcement of sanitary regulations.
      An intensive educational campaign spread health information among the population.
      These efforts overcame the serious health dangers that characterized the early
      weeks of the ghetto, and for the remainder of the existence of the ghetto
      prevented outbreaks of epidemic diseases that otherwise might have resulted in
      catastrophic death rates.

PMID- 20684100
TI  - Medicare physician fees: the data behind the numbers.
AB  - Medicare's physician fee schedule distributes nearly $60 billion annually and is
      a critical determinant of individual physicians' incomes, beneficiaries' access
      to health care services, and Medicare spending, as well as the basis for
      physician fees used by many private payers. The Centers for Medicare & Medicaid
      Services (CMS) relies on data derived from expert judgment and other sources to
      update the fee schedule. Although CMS's methods and data for maintaining the fee
      schedule have improved over the years, concerns remain about medical specialty
      society involvement and the lack of an effective "counterweight" to vested
      interests in establishing and updating the relative values in the fee schedule.
      This issue brief reviews the data used in the fee schedule, including the new,
      multispecialty practice expense survey, and the role of the American Medical
      Association/Specialty Society Relative Value Scale Update Committee.

PMID- 20684101
TI  - The "Mindless Years"?: a reconsideration of the psychological dimensions of the
      Holocaust, 1938-1945.
AB  - This article examines the frayed relationship between psychology and Holocaust
      history and its consequences for scholarship, arguing the need for a
      reconciliation between the fields. The causes for the split are traced in part to
      a reductionist approach to methodological, conceptual, and moral issues common in
      psychology, an approach particularly misleading in work on the Holocaust. On the
      other hand, historians continue to make the subjective motivations of both
      perpetrators and victims a central concern-an implicitly psychological question.
      Consequently, implicit (mis)conceptions of psychology affect-distort-long
      standing historical debates. Zuckier argues that a misconception of psychological
      intentionality (unwittingly shared by both opposing sides) has set a wrong
      historical agenda and led to "fluke-and-freak" accounts of the Holocaust in which
      the protagonists are alternately said to act out their essential dispositions or
      to be the victims of their own psychological compulsions and accidental history.
      The article explores the effects of such conceptions in the study not only of
      perpetrators and victims, but also rescuers, witnesses, survivors, and their
      children. It concludes with an appeal for a more differentiated interactional
      approach.

PMID- 20684102
TI  - Thematic content analyses: nomothetic methods for using Holocaust survivor
      narratives in psychological research.
AB  - The overwhelming majority of psychological research on Holocaust survivors
      follows an idiographic model, which is concerned with studying and understanding
      individual personalities and how they have been affected by their experiences.
      Most such publications emphasize pathological characteristics, use psychodynamic
      theoretical formulations, and ignore criteria of rigorous behavioral science such
      as reliability, replicability, statistical significance, and safeguards against
      researcher and subject bias. This article describes a set of alternative research
      methods in which survivor narratives are randomly sampled and then analyzed
      according to established protocols. They thus provide quantitative data through
      means of acceptable scientific rigor. Such approaches can identify reliable,
      lawful patterns applicable to groups of individuals, and provide a suitable
      alternative to (not a replacement for) qualitative case or small-group
      methodology.

PMID- 20684103
TI  - Between science and fiction: notes on the demography of the Holocaust.
AB  - The quantitative effects of the Holocaust have been the subject of much
      discussion and speculation, but rarely have they been seriously scrutinized using
      demographic methods. The first part of this article outlines the major factors
      that need to be fully examined in order to assess the short and long-term effects
      of the Shoah on the Jewish population. The second section cautiously offers
      demographic projections for the Jewish population had the Shoah never happened.
      The obviously speculative analysis presented here is open to many assumptions
      beyond those suggested by the author in this paper. The results of alternative
      projections reveal that because of the generations that were not born, high
      wartime child mortality, and the present day aging of the Jewish population,
      demographic losses continue to extend far beyond that of six million.

PMID- 20684104
TI  - Gypsies as victims of the Holocaust.
AB  - While most of the research on the Holocaust has appropriately focused on the
      suffering of the Jewish population of Axis-occupied Europe, the Gypsies also were
      targeted for extinction by the Nazis. The Gypsies as a people survived the
      campaigns directed against them in large measure because they were located in
      areas under the control of governments allied with Germany. These governments
      generally refused to participate in the extermination of the Gypsies (just as
      some did not participate in the destruction of the European Jews). The majority
      of the Gypsy population in Axis Europe was beyond the direct control of the Nazi
      extermination machinery and, as a consequence, survival rates were higher. In
      contrast the European Jews were concentrated in areas under direct German
      control, and therefore the proportion of fatalities was much higher. Geographic
      location thus was one major factor that explains the greater survival rate of the
      Gypsies compared to that of the Jews.

PMID- 20684105
TI  - Everyday life of Jews under Nazi occupation: methodological issues.
AB  - Despite the dire circumstances of Jews under Nazi occupation, individuals
      continued to persevere in their efforts to maintain patterns of everyday life. An
      understanding of daily routines may help us comprehend the reality of the
      Holocaust, but it may also contribute to the trivialization and banalization of
      the topic. To counter this danger, the methodology proposed in this article
      asserts that the individual's struggle reveals another perspective on the state
      of mind and the social order of various strata of Jewish society under Nazi
      occupation. Invoking the concepts of Berger and Luckmann in their analysis of
      understanding the knowledge of everyday life, this article examines the
      perception of reality of intellectuals in the ghetto.

PMID- 20684106
TI  - Women and genocide: notes on an unwritten history.
AB  - Whatever has been written about the history of genocide has been based mainly on
      the experiences of men. Yet women's experiences with genocide have often differed
      from those of men in terms of participation, forms of victimization, and
      consequences. This essay explores these issues, focusing In particular on the
      relationship between women and the perpetration of genocide.

PMID- 20684107
TI  - The social and cultural life of the prisoners in the Jewish forced labor camp at
      Skarzysko-Kamienna.
AB  - The article discusses the social and cultural life among the Jewish prisoners at
      the Skarzysko-Kamienna forced labor camp in central Poland. The activities
      included organized observances of religious and national customs and creative
      arts and performances of many kinds. The activities served several functions for
      the artists and audiences. Whether as a source of income in the struggle for
      physical survival, or as a psychological escape from the terrible reality of
      daily life in the camp, or as a unifying element for the fragmented prisoner
      population, or as a from of political resistance, these social and cultural
      activities in the camp constitute a singular phenomenon in the history of the
      Holocaust.

PMID- 20684108
TI  - Psychological perspectives on the perpetrators of the Holocaust: the role of
      situational pressures, personal dispositions, and their interactions.
AB  - Three psychological approaches attempting to explain the behavior of the
      perpetrators of the Holocaust are reviewed and evaluated. The first is a
      situational approach building largely on the laboratory experiments of the social
      psychologist Stanley Milgram. The second is an approach focusing on the personal
      dispositions of the perpetrators, the primary example being work which has tried
      to find evidence of psychopathology among the Nazi leaders. The third is an
      interactional approach-one that sees the Nazis' murderous actions as a product of
      both situational pressures and personal dispositions. Among the last, the work of
      Helen Fein stands out because, through its main findings, it encompasses the
      diversity of Nazi destructiveness: both the enthusiastic serf-initiated horrors
      of the hate-driven antisemite and the impersonal, routinized actions of the
      bureaucrat carrying out the orders of his superior.

PMID- 20684109
TI  - Fear and comfort: the plight of hidden Jewish children in wartime-Poland.
AB  - Jewish children in hiding during the Holocaust undoubtedly share many
      experiences. These have affected their lives in various ways. In general, many,
      if not most, formerly hidden have learned to master their painful childhood
      memories and paradoxically harness these to further their adult development As a
      person dealing these past nine years in the study of the Gentile rescuers of both
      Jewish adults and children, from countries of different political, economic and
      cultural backgrounds, and of various and even conflicting attitudes towards the
      Jewish population in their midst, I found the experiences of Jewish children in
      hiding in Poland to be especially overwhelming and heart-strinng. In that
      country, the various affectations were sharper and more accentuated than those
      experienced by their counterparts in West European countries; that is, the
      sufferings and fears, as well as the love and comfort which these children
      underwent in Poland were far more pronounced than similar situations elsewhere on
      the German-controlled continent.

PMID- 20684110
TI  - The destruction of human identity in concentration camps: the contribution of the
      social sciences to an analysis of behavior under extreme conditions.
AB  - This article examines the question of whether it is possible to use categories of
      the social sciences when analyzing the behavioral patterns of concentration camp
      detainees. The study illustrates that despite widespread arbitrary and harassing
      treatment, not only chance and chaos were at the root of the inmates' attempts
      and strategies to assert themselves in the camps. There rather was an emergence
      of social groups and strata who had different possibilities of action and chances
      of survival. The author objects to an absolutizing of psychoanalytical approaches
      which would mostly involve unverified hypotheses concerning the inmates'
      psychological way of coping with their experience.

PMID- 20684111
TI  - Managing intensive care.

PMID- 20684112
TI  - The theory and prevention of genocide.
AB  - The development of a social-scientific theory of genocide has been neglected by
      most social scientists, viewed with suspicion by several Holocaust scholars, and
      advanced in a fragmentary and confused manner by those few scholars who have
      committed themselves to this task. This paper attempts to clarify the problems
      which confront those attempting a social theory of genocide and proposes
      solutions which, while recognising a necessary pluralism in social science
      methodology, seek to clear the way for the advance of theory construction. A
      theoretical account of genocide is proposed which draws on work in the social
      sciences and in genocide studies. It is argued that this account provides the
      grounds for cautious optimism about the development of a theory of genocide. A
      precondition for the fulfilment of this optimism is the abandonment by both
      opponents and advocates of social-scientific approaches to the understanding of
      genocide of the outdated assumption that social science must be informed by a
      positivist philosophy. The project of preventing genocide should not rest upon
      positivist illusions which are incompatible with the conception of moral agency
      which we must employ both in our ethical judgments and in our social-scientific
      understanding of genocidal evil.

PMID- 20684113
TI  - Acute care surgery: the natural evolution of trauma surgery.

PMID- 20684114
TI  - The best and worst of times. Interview by Anne Manchester.

PMID- 20684115
TI  - Medical selection: Auschwitz antecedents and effluent.
AB  - Medical selection in Auschwitz represents the penultimate application of the
      traditional paradigm of medicine; the physician as gatekeeper, and decision
      maker. The historical evolution of that role is considered in the context of
      public health, medical police, quarantine and immigration. In Nazi Germany the
      physician was assigned responsibility for selection on behalf of the state. The
      ethical implications of medical selection are considered in the context of
      medicine today in an age of sophisticated biotechnology, constrained resources,
      and an aging population; an age in which the medical profession has yet to
      establish a fundamental system of values.

PMID- 20684116
TI  - Gender distinction in the genocidal process: a preliminary study of the Armenian
      case.
AB  - The relationship between gender and genocide remains ambivalent. A preliminary
      analysis of in-depth interviews with 14 Armenian female survivors reveals a
      gender distinction in the 1915 Turkish genocide of the Armenians. The genocidal
      process was gender-based. Men were instantaneously killed and women and children
      were deported. However, members of both sexes acted as perpetrators and
      collaborators. Few men and women acted as rescuers.

PMID- 20684117
TI  - The art of the children of Terezin. A psychological study.
AB  - This study is an analysis of the content and symbolism inherent in the art of
      children who were imprisoned in the Terezin Concentration Camp during the
      Holocaust. Its purpose is to attempt to understand how they perceived and sought
      to cope with the conditions of their lives at the camp, and to assess the degree
      of psychic damage suffered by them. The major themes are food, family and
      freedom, intense feelings of claustrophobia, a sense of the fragility of one's
      physical existence and the lack of human value of the camp inmates. Impressive is
      the absence of evidence of serious mental illness and aggression. It may be
      inferred that these manifestations did not have survival value.

PMID- 20684118
TI  - The politics of famine: American government and press response to the Ukrainian
      famine, 1932-1933.
AB  - The Soviet Ukraine suffered a man-made famine in 1932-1933 during which millions
      died. This was part of the central government's attack on Ukrainian nationality
      and culture. The United States Government received numerous contemporary
      intelligence reports on the famine from its European embassies, but chose not to
      acknowledge the famine publicly. Similarly, leading members of the American press
      corps in the Soviet Union willfully covered up the famine in their dispatches. In
      both cases, political considerations relating to the establishment of diplomatic
      relations with the U.S.S.R. seem to have been critical factors in this cover-up.

PMID- 20684119
TI  - Christian charity: the Unitarian Service Committee's relief activities on behalf
      of refugees from Nazism, 1940-5.
AB  - The Unitanan Service Committee (USC) was one of a number of American Christian
      organizations which aided refugees, mostly Christians, during the Nazi period.
      Although modelled somewhat after the Quakers' American Friends Service Committee,
      the USC differed from this group in its opposition to neutrality and openly
      expressed support for the Allied cause Despite its late start (1940) in overseas
      work, the USC was very energetic and creative in aiding refugees. The Committee
      was also the only relief agency in Lisbon specializing in care for illegal
      refugees. This case study points to how much might have been accomplished had
      there been greater determination on the part of more people to aid the innocents
      endangered by the Nazis.

PMID- 20684120
TI  - The impact of cultural context on the mental health of Jewish concentration camp
      survivors.
AB  - This study examines whether the area of settlement of Jewish concentration camp
      survivors has an impact on their mental health. Using the Langner mental health
      index, survivors in Israel are compared with an earlier study of survivors in
      Montreal. Survivors in Israel score higher than their Montreal counterparts,
      indicating a greater degree of mental impairment. The suggestion is raised that
      the numerous memorials and ceremonies commemorating the Holocaust in Israel
      increase the salience of the survivors' remembrance of the past. These persons
      may, therefore, be more sensitive to the perpetually tense military situation
      prevalent in the country, and this may have a deleterious effect on their mental
      health.

PMID- 20684121
TI  - Revisiting cell adhesion and migration molecular pathways: Focus on the role of
      transmembrane domains interactions.

PMID- 20684122
TI  - Frailty should be assessed using validated scales.

PMID- 20684124
TI  - Integrated malignant and non-malignant palliative care in Scotland.
AB  - The Scottish Government promotes equity in palliative care delivery in Living and
      Dying Well (Scottish Government, 2008). Ten nurses, working in the community in
      Western Isles, participated in focus groups to discuss how palliative care needs
      of islanders may best be met. Analysis used Framework (Ritchie et al, 2003) and
      identified needs of the family unit, teamwork, specialist skills and rural issues
      as the main themes. Nurses feared burgeoning caseloads and expressed a need for
      time to share and develop knowledge and skills. They described a collaborative
      model of care in keeping with that recommended by Scottish Partnership for
      Palliative Care (2006). Further research could seek the views of island patients
      and families requiring long-term palliative care.

PMID- 20684123
TI  - The effects of growth hormone deficiency and growth hormone replacement therapy
      on intellectual ability, personality and adjustment in children.
AB  - Traditionally, it has been assumed that intellectual development in children with
      growth hormone deficiency (GHD) is distributed between ranges of a normal
      population based on the observation that it does not differ substantially from
      that of children of the same age. Nevertheless, few studies have investigated
      this assumption. This Spanish Collaborative study was prospectively planned with
      two main purposes: to study a possible influence of GHD on intelligence quotient
      (IQ), personality traits and adaptative capacity and to study the evolution of
      these parameters during substitution therapy with growth hormone (GH). Although
      the overall intellectual ability of children with GHD is comparable to that of a
      normal reference population, some areas such the motor-component scale (evaluated
      by McCarthy test) and performance IQ (evaluated by WISC-R) were below the mean at
      the beginning of the study, showing significant improvement during therapy.
      Emotional adjustment (normal at study start) also improved significantly during
      treatment. Females showed better adjustment capacity before and during GH
      therapy. Longer studies with an increased number of cases are needed to confirm
      these effects of GHD and its treatment in children.

PMID- 20684125
TI  - [A pill for social suffering: a simple advancement].

PMID- 20684126
TI  - [Clinical management of primary headaches: interdisciplinary guidelines].
AB  - Primary headaches, whose aetiologies cannot be identified by current diagnostic
      methods, represent the most frequent headaches and must be distinguished from
      secondary or symptomatic headaches, e.g. related to traumatic, vascular,
      inflammatory or neoplastic processes. Only an appropriate treatment will meet the
      expectations of patients, for who even a mild headache may generate important
      fears and handicaps. Medical history and physical examination form the basis for
      targeting the right diagnosis before any biological or radiological testing. The
      article presents guidelines implemented at the Geneva University Hospitals by the
      Pain Network of the institution. Therapeutic modalities and recommendations
      concerning the need for specialized assessments are presented to provide a
      framework in both emergency situation and long-term care.

PMID- 20684127
TI  - [Self medication with analgesics: what are the risks?].
AB  - Analgesics are among the most widely consumed drugs, whether they have been
      prescribed by a healthcare provider or used as self-medication. Their use can be
      associated with a toxicity risk, in particular in elderly patients with comorbid
      conditions and polypharmacy, which is synonymous with potential drug
      interactions. These risks are particularly high given the fact that patients are
      usually unaware of them, which highlights the necessity for thorough counselling
      and a precise drug history. In this article, we discuss the risks that are
      inherent to self-medication with paracetamol, nonsteroidal antiinflammatory drugs
      and opioids. The particular case of medication overuse headache is mentioned as
      an entity which is characterized by a dependency-like behaviour towards the
      concerned analgesics.

PMID- 20684128
TI  - [Immediate hypersenstivity reactions to nonsteroidal anti-inflammatory drugs:
      allergy or pseudo-allergy?].
AB  - Immediate hypersensitivity reactions to nonsteroidal anti-inflammatory drugs
      (NSAID) can be classified into allergic (immune-mediated) reactions to a single
      NSAID molecule or a group of chemically similar structure, and pseudo-allergic
      (or intolerance) linked to pharmacological Cox-1 inhibition. Distinction between
      these two entities is clinically difficult but important to quantify risks
      associated with the prescription of another NSAID. Oral challenge test can help
      the diagnosis. In case of an allergic reaction, a structurally chemically
      different NSAID will be offered. In case of a pseudo-allergic reaction, cross
      sensitivity between non-selective NSAID is common; in these patients selective
      inhibitors of Cox-2 may be considered. If necessary, tolerance to acetylsalicylic
      acid can be induced, but has to be maintained by continous administration of the
      drug.

PMID- 20684129
TI  - [Juvenile low back pain: clinical approach in 2010].
AB  - The first part of this article reviews the evolution of diagnostic issues
      regarding low back pain (LBP) in children and adolescents in recent years. The
      attitude recommended in the literature has been adapted to current
      epidemiological data showing that non specific LBP is largely prevalent in these
      age groups, much like in adult populations. Thus, it seems reasonable to avoid an
      overly aggressive therapeutic attitude, especially in the adolescent population.
      The second part of the article is devoted to non specific LBP and summarizes
      recent studies. These data show that the impact of LBP on the quality of life in
      children and adolescents is very low, with the exception, however, of a small
      subgroup of adolescents suffering generalized pain in conjunction with LBP.

PMID- 20684130
TI  - [Adult scoliosis: a misknown etiology of low back pain in the elderly
      population].
AB  - Degenerative scoliosis is often unappreciated in all-day clinical practice,
      however more and more frequent in the elderly population and deserves particular
      attention. This article aims to provide practitioners with practical guidelines
      to track these patients, organise radiological assessment in accordance with
      clinical situations, and implement an adequate therapeutic strategy.

PMID- 20684131
TI  - [Pain and its treatment in prison].
AB  - Frequency of pain in detention contrasts with the scarcity of the literature
      about this precise topic. Prescription practice makes a point of best observing
      the fundamental principles of penitentiary medicine, including the equivalence of
      care. Addictive pathology is highly prevalent. Analgesia for individuals with
      physical dependence to opioids requires specific knowledge and skills to avoid
      symptom underestimating. In case of in-cell prescription drugs accumulation, pain
      killers are among the most frequently found. This stirs up a questioning on good
      medical practice, prescription's appropriateness and both symbolic and practical
      roles of these pilings. Current knowledge is insufficient for answering to it.
      For the moment, the classical guideline of multidimensional management applies.

PMID- 20684132
TI  - [Actual therapeutic options in the treatment of generalized anxiety disorders].
AB  - Among a variety of drugs used in the treatment of anxiety disorders,
      benzodiazepines and antidepressants such as selective serotonin reuptake
      inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs)
      are at present the most established and prescribed. In fact, recent guidelines
      recommend the antidepressants SSRI and SNRI as well as pregabaline, a newly
      developed drug, as the 1st choice treatment in generalized anxiety disorder
      (GAD). However, antidepressants have several disadvantages (latency of onset of
      action, adverse effects and drug interactions) that should not be neglected.
      Pregabaline is a drug with a new mechanism of action. Clinical studies up to now
      indicate a rather rapid and efficient anxiolytic effect comparable to that of
      benzodiazepines, with no risk of abuse. Pregabaline has been recently introduced
      in Switzerland for the treatment of GAD.

PMID- 20684133
TI  - [What's new in integrated health care delivery networks].

PMID- 20684134
TI  - [Normality of the female libido (1)].

PMID- 20684135
TI  - [Vuvuzela - an unforgettable sound].

PMID- 20684136
TI  - [Bioethics: Kant finally is reduced to silence? (2)].

PMID- 20684137
TI  - [Hepatitis E: first steps towards a treatment].

PMID- 20684138
TI  - [Full body avatar control].

PMID- 20684139
TI  - Minocycline is effective and cosmetically preferred to clofazimine by leprosy
      patients in New York.

PMID- 20684140
TI  - Approaching psoriasis differently: patient-physician relationships, patient
      education and choosing the right topical vehicle.
AB  - Psoriasis is a common, frustrating problem for dermatologists and patients. Long
      held notions about the need to use thick, greasy corticosteroid ointments for
      psoriasis contributed to frustration for many patients. Fortunately, the general
      approach to managing psoriasis is changing. The purpose of this article is to
      describe key components of psoriasis management with a focus on the changing
      paradigm for treating the disease. In addition to making the right diagnosis and
      prescribing the right treatment, key elements of psoriasis management include
      establishing a strong physician-patient relationship, educating patients about
      the disease and recognizing the importance of adherence to topical treatment. In
      light of the tendency toward poor adherence, use of a fast-acting agent in a
      vehicle that patients are willing to use is critically important for successful
      disease management.

PMID- 20684141
TI  - Scalp psoriasis: an overview of the disease and available therapies.
AB  - The scalp is one of the regions of the body most commonly affected by psoriatic
      lesions. While the head represents only 10 percent of the body's surface area,
      the consequences of scalp psoriasis are disproportionate to the area, as it can
      be seriously debilitating and presents social and emotional distress to the
      affected individual. Scalp lesions are often well-demarcated and may have thick
      gray or white scale; patients with scalp psoriasis frequently complain of
      pruritus and shedding of scale. Current treatment modalities--including
      phototherapy, topical corticosteroids, topical vitamin D analogues and
      conventional systemic therapies--have produced unsatisfactory results for
      patients with moderate-to-severe scalp psoriasis due to difficulties in
      administration to the disease site, poor compliance, toxicity and inadequate long
      term efficacy. The emergence of biologic therapies as an effective modality for
      the treatment of plaque psoriasis may provide another option for patients
      suffering from plaque psoriasis of the scalp.

PMID- 20684142
TI  - Statins in skin: research and rediscovery, from psoriasis to sclerosis.
AB  - Statins, initially developed as antimicrobials, are primarily considered
      cholesterol-lowering agents. Recently, researchers discovered anti-inflammatory
      properties of statins. Studies on the effects of statins and the alterations
      noted include: bench work that supported a Th1/Th2 skew to Th1, altered
      lymphocyte migration, inhibition of MHC-II induction and cytokine release on
      antigen-presenting cells, inhibition of mast cell degranulation and inhibition of
      Th17 cells and IL-17 production. In addition to the anti-inflammatory properties,
      statins have been found to induce apoptosis in melanoma models. The potential
      therapeutic value of statins is illustrated in the management of alopecia areata,
      atopic dermatitis, psoriasis, systemic lupus erythematosus, cutaneous T-cell
      lymphomas, cutaneous melanoma, mastocytosis and more. This manuscript presents a
      comprehensive review of statins and their potential dermatologic application.

PMID- 20684144
TI  - Treatment patterns and perceptions of treatment attributes, satisfaction and
      effectiveness among patients with psoriasis.
AB  - Psoriasis is a chronic autoimmune condition that affects over 7 million
      Americans, approximately 1-3 percent of the population. Although there are a
      number of treatment options currently available, little is known about the
      treatment patterns of patients. Using data from 1,006 psoriasis sufferers, the
      aim of the present study was to analyze patients' treatment timeline, as well as
      their perceptions about these treatments. Most respondents were white, female and
      had health insurance. The results suggested that over-the-counter (OTC) and
      prescription topicals were the most common initial treatments, but systemic orals
      and biologics were the most common treatments for patients who required a third
      line or fourth-line treatment (and for patients with greater severity). Treatment
      dissatisfaction was relatively high, with very few positive attributes associated
      with the current treatment options. Overall, this study suggests that treatment
      options vary (at a statistically significant level) as a function of severity,
      and many patients, despite the choices in the number and quality of treatment
      options, are generally dissatisfied.

PMID- 20684143
TI  - Long-term safety and efficacy of etanercept in patients with psoriasis: an open
      label study.
AB  - BACKGROUND: In two previous phase 3 studies, up to 60 weeks of etanercept therapy
      significantly improved the symptoms of psoriasis and was well tolerated.
      OBJECTIVE: To evaluate the long-term safety of etanercept in an open-label
      extension study for up to 72 weeks in patients with moderate-to-severe plaque
      psoriasis. METHODS: A total of 912 patients received 50 mg subcutaneous
      etanercept once weekly (OW) for the first 12 weeks of this extension study.
      Thereafter, eligible patients could maintain the 50 mg QW dose (n = 321) or
      escalate to 50 mg twice weekly (BIW; n = 591) anytime thereafter based on one of
      three predetermined criteria. RESULTS: Etanercept was well tolerated during 1056
      patient-years of exposure; no difference was observed between the 50 mg QW and 50
      mg BIW dosages in rates of adverse events and infections. Improvement in skin
      disease was maintained throughout the study. Patients who stopped and then
      restarted etanercept also showed improvement in psoriasis. CONCLUSION: Psoriatic
      patients continued to benefit from open-label etanercept treatment, both
      continuous and interrupted therapy, which was generally well tolerated after a
      combined 2.5 years of experience.

PMID- 20684145
TI  - Prospective new biologic therapies for psoriasis and psoriatic arthritis.
AB  - Psoriasis and psoriatic arthritis are immune-mediated, chronic, inflammatory
      diseases that place a heavy burden on the lifestyle of patients affected. Current
      understanding of the pathophysiology of these conditions has produced very
      encouraging new medical developments, largely a consequence of research that has
      targeted precise elements of the immune cascade, expanding the repertoire of
      therapeutic options available to dermatologists. Promising new treatments, such
      as antibodies to interleukin-12 and -23, show superior efficacy and safety in
      treating psoriasis; the more sophisticated tumor necrosis factor antagonists
      significantly improve symptoms of rheumatic and psoriatic arthritis and may also
      be effective in the treatment of plaque psoriasis. In this article, innovative,
      new treatments for psoriasis and psoriatic arthritis are critically reviewed.

PMID- 20684146
TI  - Efficacy of 15% azelaic acid in psoriasis vulgaris: a randomized, controlled
      clinical trial.
AB  - BACKGROUND: Psoriasis is a common disorder affecting 1-3 percent of the general
      global population. Many therapeutic modalities have been suggested for treatment
      of this condition, but still there is no definite treatment for this disease. The
      objective in this study was to evaluate the efficacy of topical azelaic acid gel
      versus placebo in the treatment of psoriasis vulgaris. PATIENTS, MATERIALS AND
      METHODS: This study was a single-blinded randomized clinical trial. Overall, 31
      patients were selected and the left or right sided lesions of the patients were
      randomized to receive either 15% azelaic acid or gel twice daily for a one-month
      period. Two symmetrical lesions with almost similar severity in every patient
      were selected and considered as index lesions to evaluate lesion response to
      treatment. The severity of erythema, scaling, hyperkeratosis and pruritus of the
      index lesions were scored in range of 0-3 for each lesion by the investigator at
      the baseline and follow up visits. The percent of involvement of each side of
      body was also measured using rule of nines. The collected data were analyzed
      using statistical tests including Mann-Whitney and ANOVA tests. RESULTS: There
      was no significant difference between the two groups before treatment (P > 0.05).
      After treatment, however, except pruritus, there was significant difference
      between the two groups (P < 0.05). There was no significant difference regarding
      total psoriasis score between the two groups before treatment (P > 0.05). After
      treatment, however, there was significant difference between the two groups (P <
      0.05) in favor of more efficacy for azelaic acid. There was no significant
      difference regarding percent of body involvement between the two groups before
      treatment (P > 0.05). After treatment, however, there was a significant
      difference between the two groups (P < 0.05) in favor of more efficacy on the
      part of azelaic acid gel. DISCUSSION: The results of our study showed that 15%
      azelaic acid gel was effective in reduction of purities, scaling and
      hyperkeratosis of psoriasis plaques. This treatment was also effective in
      reduction of skin involvement with psoriasis. It is recommended that a longer
      study be performed that can better evaluate the efficacy of this treatment
      against plaque-type psoriasis.

PMID- 20684147
TI  - Short- and long-term safety assessment of a two-compound ointment containing
      calcipotriene/betamethasone dipropionate (Taclonex/Daivobet/Dovobet ointment):
      hypothalamic-pituitary-adrenal axis function in patients with psoriasis vulgaris.
AB  - The two-compound ointment (Taclonex/Daivobet/Dovobet ointment) combining
      calcipotriene 50 microg/g and betamethasone 0.5 mg/g (as dipropionate) is very
      effective in the treatment of psoriasis vulgaris. There is a possibility that
      hypothalamo-pituitary-axis (HPA) suppression may occur if the potent
      corticosteroid component is absorbed to a sufficient extent. The effect of the
      two-compound ointment on HPA axis function was assessed in two studies. Study 1
      was a four-week, double-blind study which compared the effects of the two
      compound ointment with betamethasone 0.5 mg/g (as dipropionate; Diprosone)
      ointment in 24 patients with extensive psoriasis (involving 15-30% of the body
      surface area). No patients receiving the two-compound ointment had HPA axis
      suppression. Study 2 assessed HPA axis function after four and 52 weeks in a
      subset of patients (n = 19) participating in a long-term safety study. Patients
      were treated with the two-compound ointment for the first four weeks followed by
      48 weeks of treatment as needed with either 1) two-compound ointment; 2) two
      compound ointment alternating with calcipotriene four-weekly or 3) calcipotriene.
      No patients using the two-compound ointment for all 52 weeks or alternating four
      weekly with calcipotriene had HPA axis suppression.

PMID- 20684148
TI  - Use of biologic agents in pediatric psoriasis.
AB  - Psoriasis affects approximately 2 percent of the population. Approximately 30-45
      percent of those affected first experience symptoms during childhood or
      adolescence. Although biologics have proven to be a relatively safe and effective
      treatment option for adults with psoriasis, limited information is available
      regarding the use of biologic agents in pediatric patients with psoriasis. The
      authors attempt to assess and summarize the available data on the use of biologic
      agents in patients under the age of 18, regardless of the indication, as well as
      to examine the limited available data on the use of biologics for psoriasis in
      the pediatric population. In doing so, the authors aim to provide guidance on the
      safety and efficacy of biologic therapies in pediatric patients with psoriasis.
      The authors' findings suggest that biologic agents should be considered for use
      solely in children with psoriasis that is refractory to conventional therapies,
      including children currently with severe, widespread, refractory pustular, plaque
      or psoriatic arthritis. Of all the currently available biologics, etanercept
      appears to have resulted in fewer and less severe side effects compared to
      infliximab in the juvenile rheumatoid arthritis population. In addition, while
      biologics are generally safe and effective in the pediatric population, serious
      adverse events (including infection), have been reported in the literature and
      should be taken into account before beginning treatment with any biologic agent.
      The physician and parents of the patient must carefully consider the risk-benefit
      ratio when deciding whether to use these medications. Additional randomized,
      controlled trials are needed to adequately assess the safety and efficacy of
      biologic medications for childhood psoriasis.

PMID- 20684149
TI  - The usefulness of narrowband UVB as a monotherapy for the treatment of chronic
      plaque psoriasis.
AB  - OBJECTIVE: To assess the efficacy and safety of narrowband ultraviolet B (UVB)
      phototherapy in dark-skinned Saudi patients with chronic plaque psoriasis.
      PATIENTS AND METHODS: This prospective study was performed on 63 patients of
      chronic plaque psoriasis attending Qassim University clinics from May 2004
      through June 2009. Narrowband UVB irradiation was done three times per week using
      the 311 +/- 2 nm wavelength. RESULTS: Approximately 79 percent of patients
      achieved disease clearance (i.e., 90% or more reduction in PASI scores). The
      response to treatment was significantly better in females compared to males. No
      serious side effects were observed. CONCLUSION: The narrowband UVB phototherapy
      was found to be safe and effective in darker-skinned Saudi patients with chronic
      plaque psoriasis, especially among females. A longer period of treatment (minimum
      of six months) is recommended for complete clearance of psoriasis.

PMID- 20684150
TI  - An evidence-based review of the efficacy of topical antihistamines in the relief
      of pruritus.
AB  - OBJECTIVE: To critically review the body of clinical trials refuting or
      supporting the efficacy of topical antihistamines in the relief of pruritus.
      DESIGN: Review of PubMed from January 1950 through September 2009 and the
      Cochrane Database of Systematic Reviews to identify therapeutic trials of topical
      antihistamines in the relief of pruritus. MAIN OUTCOME MEASURES: All randomized
      controlled trials or clinical trials of topical antihistaminic compounds used in
      the treatment of pruritus. The authors found 19 trials throughout the literature.
      The quality of each trial was ranked by applying a modified version of Sackett's
      criteria for clinical evidence. Grade A trials are large, randomized, double
      blind, placebo-controlled studies with low false-positive (alpha) and low false
      negative (beta) errors. Grade B studies are also randomized, double-blind,
      placebo-controlled studies, but include a small number of patients. Grade C
      trials lack one or more of the following criteria: randomization, placebo control
      or blinding. RESULTS: Only four large, randomized, double-blind, placebo
      controlled clinical trials with definitive conclusions (grade A) support the use
      of topical antihistaminic agents, specifically topical doxepin, for relief of
      pruritus. Of seven grade B trials, four supported the efficacy of topical
      antihistamines while three refute their use in relieving pruritus. One grade B
      trial was inconclusive. All remaining trials (grade C) lacked placebo controls or
      randomization, or contained fewer than 20 patients in each treatment group.
      CONCLUSION: While topical antihistamines are widely prescribed for the treatment
      of pruritus, the evidence to support their use is mixed. Topical doxepin has been
      demonstrated to reduce pruritus. Evidence is lacking, however, for other topical
      antihistamines, including diphenhydramine (Benadryl), that are widely used and
      available without a prescription.

PMID- 20684151
TI  - Irritation potential of tretinoin gel microsphere pump versus adapalene plus
      benzoyl peroxide gel.
AB  - This single-center, investigator-blinded, randomized, split-face, phase 4 study
      compared the irritation potential of tretinoin gel microsphere (TGM) 0.04% in a
      pump dispenser with adapalene 0.1% plus benzoyl peroxide 2.5% gel (ADA-BPO
      0.1%/2.5%) in a panel of 170 subjects. Participants were treated with TGM 0.04%
      pump on a randomly assigned side of the face and ADA-BPO 0.1%/2.5% gel on the
      other side of the face daily for three consecutive weeks. Expert grader
      assessments of erythema and dryness and subject self-assessments of
      burning/stinging and itching were conducted daily, except on weekends. TGM 0.04%
      pump was associated with better facial tolerance as demonstrated by significantly
      less cumulative erythema (P < 0.0001), dryness (P < 0.0001), burning/stinging (P
      < 0.0001) and itching (P < 0.0001) compared with ADA-BPO 0.1%/2.5% gel. While
      both agents were well tolerated by most patients, TGM 0.04% pump demonstrated
      significantly better tolerance than ADA-BPO 0.1%/2.5% gel in both neurosensory
      parameters and signs of contact irritation.

PMID- 20684152
TI  - Progressive multifocal leukoencephalopathy in two psoriasis patients treated with
      efalizumab.
AB  - Progressive multifocal leukoencephalopathy (PML) is a rare neurological disorder
      that occurs almost exclusively in immunocompromised individuals by reactivation
      of the John Cunningham virus (JC virus), a polyomavirus found latent in more than
      80 percent of healthy adults. Efalizumab, an immunosuppressive monoclonal
      antibody targeting T cells, has been used for treatment of moderate-to-severe
      chronic psoriasis. The authors describe two cases of PML that occurred in
      patients < or = 70 years old treated with efalizumab for more than three years.
      Both presented with symptoms resembling cerebral infarction (slurred speech,
      reduced motor control, personality changes) and were assessed for evidence of
      stroke. Multiple magnetic resonance images over successive weeks demonstrated
      progression of cerebral abnormalities. PML was diagnosed, and the presence of JC
      virus was confirmed in spinal fluid samples. Both patients died shortly after
      diagnosis. Dermatologists treating patients with immunosuppressive agents should
      be alert for the symptoms of PML and seek immediate consultation with a
      neurologist should symptoms arise.

PMID- 20684153
TI  - A case of bupropion-induced Stevens-Johnson syndrome with acute psoriatic
      exacerbation.
AB  - Bupropion is a very popular medication prescribed to millions of patients
      globally for depression (Wellbutrin, GlaxoSmithKline, Research Triangle Park, NC)
      as well as an aid in smoking cessation (Zyban, GlaxoSmithKline, Research Triangle
      Park, NC). It has been reported to have some common dermatologic side effects,
      such as pruritus, urticaria and serum-sickness like reaction. The authors report
      a case of bupropion-induced Stevens-Johnson syndrome (SJS) with a concomitant
      acute psoriatic exacerbation in a 56-year-old woman, who began taking bupropion
      for treatment of depression. While the United States (U.S.) prescribing
      information for bupropion does include SJS as a rare potential side effect, it
      does not mention worsening of psoriasis. Physicians should be aware of the
      potential life-threatening adverse effects of this commonly prescribed medication
      as well as the risk in patients with known psoriasis.

PMID- 20684154
TI  - Development of Hodgkin's lymphoma under bexarotene treatment for Sezary syndrome
      and review of the literature.
AB  - There are several reports of patients who developed extracutaneous lymphoma after
      they started bexarotene treatment. The authors report a case in which the
      initiation of bexarotene therapy for Sezary syndrome was temporally associated
      with the development of Hodgkin's lymphoma despite improvement in cutaneous signs
      and symptoms. It is possible that bexarotene may contribute to the development of
      extracutaneous lymphoma. Although bexarotene therapy may relieve symptoms and
      signs of cutaneous T-cell lymphoma, careful examination of the lymph nodes during
      treatment is recommended.

PMID- 20684155
TI  - Six patients with early-stage cutaneous T-cell lymphoma successfully treated with
      topical 5-fluorouracil.
AB  - Topical 5-fluorouracil (5-FU) has been used in the treatment of various benign
      and malignant tumors of the skin, but only few address its therapeutic value on
      cutaneoues T-cell lymphoma. (CTCL). The authors report six cases of early stage
      CTCL responded to topical 5-FU. All of these patients (four females and two
      males) with early stage CTCL (1A = 4; 18 = 1; 2B = 1) had good response to
      topical 5-FU following three to 18 months' treatment. Four patients achieved
      complete response (CR) and two patients responded partially (PR). Tolerance to
      the treatment was good, with the exception of mild irritation, with no patients
      reporting serious side effects. The overall efficacy, relatively modest price and
      low incidence of side effects indicate that topical 5-FU has a place for
      treatment of early stage CTCL.

PMID- 20684156
TI  - Localized argyria secondary to acupuncture mimicking blue nevus.
AB  - The typical clinical manifestation of localized cutaneous argyria is a blue
      grayish asymptomatic macule, which may be caused by occupational exposure,
      topical treatment, dental amalgams and alternative medicine therapies. The
      lesions often are clinically indistinguishable from blue nevi and metastatic
      melanoma. The authors present a case of localized cutaneous argyria secondary to
      an acupuncture needle, emphasizing the importance of keeping this entity in mind
      in the differential diagnosis of blue-grayish pigmented lesion in a body area
      that could have been treated with acupuncture.

PMID- 20684157
TI  - Development of subacute cutaneous lupus erythematosus associated with the use of
      imiquimod to treat actinic keratoses.
AB  - The immunomodulating drug imiquimod is approved by the U.S. Food and Drug
      Administration (FDA) to treat actinic keratoses, non-facial superficial basal
      cell carcinomas and genital warts. This drug elicits its immunological response
      by binding to toll-like receptor 7 (TLR-7) on dendritic cells inducing the
      production of interferon alpha (IFN-alpha) and other inflammatory cytokines. The
      authors report the case of a 56-year-old female who developed subacute cutaneous
      lupus erythematosus (SCLE), as well as severe autoimmune retinitis following a
      vigorous response to imiquimod 5% cream that was prescribed to treat actinic
      keratoses. Given the important role of IFN-alpha in the pathogenesis of cutaneous
      lupus, it is likely that imiquimod either induced or unmasked an autoimmune
      tendency in this patient.

PMID- 20684158
TI  - Cutaneous fixed drug eruption to fluconazole.
AB  - Fixed drug eruption (FDE) is an uncommon medication-induced cutaneous reaction. A
      case of fluconazole-induced FDE is described. A 64-year-old woman presented with
      eight ovoid hyperpigmented patches on the arms, palm and lower leg that had
      recurred multiple times at the identical sites at seemingly random intervals over
      the prior six months. The clinicopathologic diagnosis strongly favored FDE,
      though the culprit medication remained elusive. Further evaluation and oral
      rechallenge confirmed the diagnosis of FDE to fluconazole. The patient had not
      related the eruption to this medication due to the short courses of therapy and
      prior use without incident. FDE to fluconazole has only been rarely reported in
      the literature. The presentation and evaluation of FDE is reviewed.

PMID- 20684159
TI  - The new melanoma staging system: what the clinician should know.

PMID- 20684160
TI  - [The Israel Defense Forces medical corps field hospital in Haiti].

PMID- 20684161
TI  - [The struggle over the establishment of the central hospital in the Negev--the
      Soroka Medical Center].
AB  - In December 1959 the Central Hospital for the Negev (today, the Soroka University
      Medical Center) opened its doors. This event was preceded by an arduous political
      battle over the Location of hospital facilities for inhabitants of Israel's
      south. On one side was the presiding Prime Minister David Ben-Gurion, who opposed
      the establishment of a hospital in Beer Sheba by the Clalit Sick Fund. On the
      other side were Beer Sheba's residents, led by David Tuviyahu--mayor of Beer
      Sheba, and Moshe Soroka--a member of the Clalit Sick Fund's management, who
      sought to bring about the immediate establishment of a hospital in the city
      itself, following the decision of the Hadassah Women's Organization to close the
      temporary hospital they had operated in Beer Sheba since 1948. The work at hand
      describes the ideological and political struggle between the two sides, the
      conflicting interests of the Government of Israel and the Labor Federation
      regarding the health needs of the city, and the factors that, in the end, led to
      the establishment of the hospital by the Federation's Clalit Sick Fund. The
      research is based on both archival material and on input from informants from the
      period who constitute primary sources.

PMID- 20684162
TI  - [Community acquired pneumonia (CAP) in children younger than 5 years of age in
      southern Israel].
AB  - BACKGROUND: Respiratory tract infections are a major cause of morbidity and
      mortality in children under the age of 5 years. The child population in southern
      Israel is divided into two main groups, Jewish and Bedouin, who differ in their
      socioeconomic status, with the Bedouin population living in lower socioeconomic
      conditions and overcrowding. Almost all children in southern Israel are treated
      at the Soroka University Medical Center. STUDY OBJECTIVE: To compare the
      epidemiological and clinical data of Bedouin and Jewish children with community
      acquired pneumonia (CAP), who were treated at the Soroka University Medical
      Center. METHODS: All chest X-rays of children under the age of 5 years, taken at
      the Pediatric Emergency room (PER) between the dates 4.11.2001 and 31.12.2007,
      were evaluated for pneumonia. Demographic and clinical data were collected to
      determine morbidity, hospitalization and mortality rates. Blood cultures and
      nasopharyngeal washes were taken to determine the pathogens of CAP. RESULTS: A
      total of 38,045 chest radiographs were evaluated; CAP was diagnosed in 5,965 of
      them (15.6%). The risk of presenting to the PER with CAP in children under the
      age of 5 years was 8.3% in Bedouin children and 5.4% in Jewish children (p <
      0.01). The cumulative risk for hospitalization due to CAP in children under the
      age of 5 years was 5.8% for the Bedouin children and 2.2% for the Jewish children
      (p < 0.01). The Bedouin children were younger than the Jewish children (43.5%
      under 1 year of age vs. 23.7% respectively, p < 0.01). Tachypnea, hypoxemia and
      mortality rates (71.9% vs. 61%, 31.7% vs. 18.6% and 3% vs. 0.3%, p < 0.01
      respectively) were higher in Bedouin children than in Jewish children.
      CONCLUSIONS: PER visits due to CAP are common, especially in Bedouin children.
      Bedouin patients were younger, with a more severe clinical course and with higher
      rates of morbidity, hospitalization and mortality than Jewish children. Improving
      living conditions, parental perception of disease severity and immunization
      programs (e.g. pneumococcal and influenza vaccine) could lead to a reduction in
      the gap between the two populations.

PMID- 20684163
TI  - [Bedside percutaneous tracheostomy in critically ill medical patients: clinical
      characteristics, outcome and complications].
AB  - BACKGROUND: Tracheostomy is a surgical procedure, frequently used in patients
      with respiratory failure requiring prolonged mechanical ventilation. It is
      associated with fewer complications and may facilitate weaning from mechanical
      ventilation. Over the past 15 years, bedside percutaneous tracheostomy (PDT) has
      been widely employed as the primary method for performing tracheostomy in
      intensive care units. However, the ideal technique and timing for this procedure
      is still controversial. OBJECTIVES: To characterize the patients who underwent
      bedside percutaneous tracheostomy (PDT) in the Medical Intensive Care Unit (MICU)
      in terms of complications, clinical characteristics upon admission, short and
      long term outcome. METHODS: This retrospective cohort study included all patients
      hospitalized at the MICU from January 2003 to December 2007 who underwent bedside
      PDT. The patients' demographic data, past diagnosis, reason for admission to the
      ICU and a wide variety of data regarding procedure performance and complications
      were retrieved from the patients' charts. The information was subsequently
      computerized and analyzed. RESULTS: The study population included 126 patients
      who underwent bedside PDT. Overall, 63.5% were men and the average age was 59.8
      years. Patients who survived for 30 days after the procedure had a lower burden
      of background morbidity as reflected by their Charlson score. The one year
      mortality rate was 56.6%, of which 70% of the patients died in the first month
      following the procedure. Overall complication rate was low and occurred in 9
      patients (7.1%). There was no procedure-related mortality. The most common
      pathogens isolated from patients' sputum were Acinetobacter spp. and Pseudomonas
      aeruginosa. The survival rate was highest among the group of patients who
      underwent tracheostomy during the first 10 days after initiation of mechanical
      ventilation. CONCLUSIONS: Bedside PDT is a simple, safe and readily available
      procedure with low morbidity rates when performed by an experienced operator.
      However, long term outcome remains poor Survival rates were lower among patients
      who underwent the procedure within ten days of mechanical ventilation.

PMID- 20684164
TI  - [Urgent removal of ruptured cerebral arteriovenous malformations in children].
AB  - In 60-80% of children with arteriovenous malformation (AVM), the first
      manifestation is an abrupt rupture resulting in intracranial hemorrhage. Some
      cases of acute rupture result in compressive hematoma, severe mass effect and
      comatose patients. Acute surgery on cerebral arteriovenous malformations (AVMs)
      has seldom been reported or used. The authors present case reports of 3 children
      (ages: five months, 7 and 9 years) who underwent craniotomy for intraparenchymal
      hematoma evacuation and AVM removal within a few hours of bleeding. All 3
      children arrived with decreased Levels of consciousness and rapid neurological
      deterioration. The 5 months old boy also suffered hypovolemic shock. The fast
      neurological worsening and mass effect of the extensive intracerebral hemorrhage
      prompted early surgical treatment. Due to active bleeding from the AVM, it was
      already resected in the acute stage using minimal invasive techniques. After one
      year of follow-up, all 3 children fully recovered with no neurological deficit.
      Post-operative angiography was performed to confirm that the malformation was
      totally removed. The management of AVM should include formal angiography, with or
      without endovascular embolization and late surgery when indicated. In this
      report, the authors presented 3 children who underwent urgent resection of the
      lesion with full neurological recovery. The management of AVM is reviewed with
      comparisons between surgical resection in the acute phase versus the late phase.

PMID- 20684165
TI  - [Principles of orientation safety body dialogue (O.S.B.D) for primary
      intervention for acute stress events].
AB  - Acute stress reaction (ASR) is related to a serious threat to the security or
      wellness of the individual physical being, or someone close to him/her. The
      incidence of ASR is predominant in the Israeli population, who in the last
      decade, are particularly exposed to terrorist or war-like events that often lead
      to many both physical and/or emotional casualties being referred to the Emergency
      Rooms or primary care clinics, necessitating expert professional intervention.
      These emotional victims are "anxiety casualties". In this article, the authors
      present basic principles and intervention procedures, which do not require
      extensive training for the professionals involved and can be implemented quickly
      and relatively simply in the treatment of these cases. The authors chose the
      acronym OSBD (in Hebrew these are the first ABCD letters) that reflect the four
      principles, O-orientation, S-security, B-body, D-dialogue. In this article, this
      concept is developed in the hope that these procedures will be both of practical
      value and available to those professionals in the Emergency Rooms, immediately
      after the patient is released into the primary care system.

PMID- 20684166
TI  - [Necrotizing cutaneous vasculitis with massive gastrointestinal bleeding
      following naproxen treatment].
AB  - Cutaneous necrotizing vasculitis is usually induced by an acute infection or
      exposure to a drug. Cutaneous vasculitis may precede severe systemic involvement,
      and may end in death. Accordingly, diagnosis of cutaneous vasculitis,
      identification of etiological factors, follow-up for systemic involvement and
      treatment are important. The authors present a case study of a 58-year-old male
      with fever and extensive eruption involving the trunk and extremities which
      appeared two days after initiation of treatment with oral naproxen. The clinical
      and histological findings were consistent with cutaneous necrotizing
      leukocytoclastic vasculitis. Two events of massive upper gastrointestinal
      bleeding occurred during treatment with systemic corticosteroids. The possible
      etiological factors and the mechanisms involved in the induction of the
      vasculitis and the gastrointestinal bleeding are discussed.

PMID- 20684167
TI  - [Target organ damage in hyperaldosteronism versus essential hypertension--the
      Beer Sheba experience].
AB  - BACKGROUND: Primary hyperaldosteronism (PAL) is the main cause for secondary
      hypertension. PAL also increases the risk for target organ damage. OBJECTIVE: To
      evaluate the rate of target organ damage in PAL patients versus essential
      hypertension patients (EHT) and to compare the rate of target organ damage in PAL
      patients who had adrenal adenoma versus patients with no adrenal adenoma.
      METHODS: The study population included patients from the outpatient hypertensive
      clinic at Soroka University Medical Center between the years 2000-2005. The
      diagnosis of PAL was performed according to standard protocol. A total of 49
      patients were diagnosed with PAL. This group of patients was composed of 12
      patients with adrenal adenoma and 37 patients with no adrenal adenoma. The PAL
      patients were compared to 40 EHT patients. RESULTS: PAL and EHT patients were
      similar in their age, gender and prevalence of diabetes mellitus. The initial
      blood pressure measurements were comparable between the two groups. There was
      significant reduction in blood pressure in PAL and EHT after initiation of
      appropriate treatment. However, the reduction in systolic blood pressure was
      higher in the PAL group. Generally, there was tendency for higher rates of target
      organ damage in the PAL group versus the EHT group. In the PAL patients with
      adrenal adenoma versus the group with no adrenal adenoma, a significant higher
      prevalence of brain involvement was observed. CONCLUSIONS: The diagnosis of PAL
      is essential in order to provide the appropriate treatment for blood pressure
      reduction and prevention of target organ damage.

PMID- 20684168
TI  - [Treatment of fungal keratitis by penetrating keratoplasty].
AB  - BACKGROUND: Fungal keratitis is basically treated by medications. Several cases
      of fungal keratitis were reported around the world to have been treated
      successfully by corneal graft--penetrating keratoplasty (PKP). Studies have shown
      that PKP is a useful treatment, preserves eye globe integrity, and rehabilitates
      vision in patients with advanced fungal keratitis. AIM: To study the use of
      penetrating keratoplasty for the treatment of severe fungal keratitis that could
      not be cured by antifungal medication. METHODS: The authors conducted a
      retrospective analysis of all cases (five cases) of severe fungal keratitis
      treated and followed-up at the Department of Ophthalmology, Soroka University
      Medical Center during 2007 and 2008, in which therapeutic PKP was performed.
      There were one male and 4 females. The age range was between 27 and 78 years. The
      follow-up period ranged from 4 to 15 months. RESULTS: Corneal graft remained
      clear during follow-up in most patients. There was no recurrence of fungal
      infection and the visual acuity ranged from counting fingers (FC) from 50 cm to
      6/36. Complications in some patients included graft rejection in one patient with
      re-graft which remained clear during follow-up period of 6 months, another
      patient had a minimal partial graft rejection and incipient cataract which didn't
      necessitate further intervention. DISCUSSION AND CONCLUSIONS: PKP is an effective
      treatment for fungal keratitis that does not respond to antifungal medication.
      Early surgical intervention before deterioration is recommended.

PMID- 20684169
TI  - [Soroka University Medical Center marks its 50th anniversary--a celebration for
      Israel's health services].
AB  - In December 2009, the Soroka University Medical Center celebrated its 50th
      anniversary. Following a difficult struggle, Soroka was established in 1959 as a
      small community hospital. Today, it is difficult to imagine the health services
      in Israel without a major hospital in the Negev. Soroka is presently providing
      quality primary, secondary and tertiary medical care to a diverse population of
      one million people from Kiryat Gat to Eilat. Soroka is the second largest
      hospital in Israel with over 200,000 emergency visits, 90,000 admissions, 32,000
      surgeries and a birth rate of over 13,000 annually. in 1974, the Ben-Gurion
      University Medical School was opened adjacent to the hospital, with the vision
      and mission of training humane and skilled physicians and pursuing advanced
      medical education and research. Within the faculty's framework and the
      infrastructure of Soroka, the largest Department of Family Physicians in Israel
      was developed in the Negev. Graduates serve in most of the Negev clinics and have
      had a tremendous impact on health in the Negev. Many of the graduates are
      currently serving in key positions in Israel's health services. A third of the
      School's graduates are annually accepted for training at Soroka. This special
      edition includes 11 articles representing the clinical research carried out in
      the hospital's various divisions. They all expose clinical implications of
      general medical science and some are related to special health problems in the
      Negev with its diverse population--old native and new immigrants, Jews and Arab
      Bedouin.We salute Soroka on its outstanding achievements.

PMID- 20684170
TI  - [International assistance during disasters: the earthquake in Haiti, January
      2010].

PMID- 20684171
TI  - [The Dead Sea--a unique resort for patients suffering from joint diseases].
AB  - The Dead Sea area is an excellent and unique resort for patients suffering from a
      wide range of inflammatory and non-inflammatory joint diseases. Factors
      contributing to the beneficial effect are the high concentration of salts and
      minerals in the Dead Sea water and in the water from springs in the area, medical
      mud, and the unique climatic conditions including high barometric pressure,
      relative low humidity and high temperatures. This review describes the various
      balneotherapy modalities and the existing body of research describing their
      utility. Balneotherapy significantly improves most patients' conditions and in
      some cases leads to complete remission of several months duration. Although of
      importance, balneotherapy is not curative. An important advantage of
      balneotherapy is the lack of serious adverse effects, and, in contrast to some
      physicians' beliefs, the scarcity of contraindications for therapy at the Dead
      Sea area.

PMID- 20684172
TI  - [Childhood genetic renal diseases in southern Israel].
AB  - Genetic kidney diseases (GKDs) are an important and well-known entity in
      pediatric nephrology. Advances in genetic and molecular approaches in the last 15
      years have enabled elucidation of the underlying molecular defects in many of
      these disorders. Herein, the authors summarize the progress that has been made
      over this period in disclosing the molecular basis of several novel GKDs which
      were characterized in this area and include Bartter syndrome type IV, type II
      Bartter syndrome and transient neonatal hyperkalemia, cystinuria and mental
      retardation, familial hypomagnesemia with secondary hypocalcemia, infantile
      nephronophthisis and familial hemolytic uremic syndrome with factor H deficiency.
      Retrospective analysis of the authors' data reveals that GKDs are over
      represented among the pediatric population in southern Israel. GKD are seen 4
      times more often than end-stage renal disease (ESRD) and comprise 38% of all
      cases of ESRD in our area. This high rate of GKD is mainly due to the high
      frequency of consanguineous marriages that prevails in this area. Understanding
      of the genetic and molecular background of these diseases is a result of a
      fruitful collaboration between the pediatric nephrologists and scientists, and
      has a direct implication on the diagnosis and treatment of the affected families.

PMID- 20684173
TI  - [Stevens-Johnson syndrome and toxic epidermal necrolysis--updates and
      innovations].
AB  - Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare
      severe cutaneous adverse reactions, usually induced by drugs. The reactions,
      which are characterized by extensive necrosis and detachment of the epidermis,
      followed by erosions of the skin and mucous membranes, are associated with high
      rates of mortality. There is growing evidence that SJS and TEN are a single
      disease with common causes and mechanisms. The present article summarizes recent
      updates and innovations related to the etiology, pathogenesis, genetic
      background, prognosis and treatment of these reactions. Among high-risk drugs
      associated with SJS/TEN, allopurinol is the most common cause of SJS/TEN in
      Europe and Israel. The prognosis of SJS/TEN can be predicted by a scoring system
      based on seven clinical and laboratory parameters. Founded on the genetic
      background of SJS/TEN, predictive tests can be used prior to starting high-risk
      medications. Treatment is still controversial, and further controlled studies are
      necessary.

PMID- 20684174
TI  - Ethical dilemmas for physicians in time of war.
AB  - During times of war, physicians are sometimes faced with the conflict of their
      professional duties to ensure the ethical principles of beneficence, non
      maleficence, patient autonomy, and self-determination, within the framework of
      the proper ethical conduct in the practice of medicine, and the obligation and
      duties placed upon the physician by the state in times of war. Many ethical
      dilemmas may occur for the physician on the battlefield or elsewhere in the war
      region, including the treatment of detainees and the priority of treating wounded
      enemy soldiers or civilians first. When physicians are faced with a conflict
      between following state or national policies and following international
      principles of humanitarian law and medical ethics, the physician should opt for
      the latter. Physicians should not participate in any way in human rights abuses
      of detainees or prisoners when deployed in a war zone. Physicians must maintain
      the principles and standards and ethical considerations of their noble profession
      at all times.

PMID- 20684175
TI  - Vitamin D supplementation and regulatory T cells in apparently healthy subjects:
      vitamin D treatment for autoimmune diseases?
AB  - BACKGROUND: Epidemiological data show significant associations of vitamin D
      deficiency and autoimmune diseases. Vitamin D may prevent autoimmunity by
      stimulating naturally occurring regulatory T cells. OBJECTIVES: To elucidate
      whether vitamin D supplementation increases Tregs frequency (%Tregs) within
      circulating CD4+ T cells. METHODS: We performed an uncontrolled vitamin D
      supplementation trial among 50 apparently healthy subjects including
      supplementation of 140,000 IU at baseline and after 4 weeks (visit 1). The final
      follow-up visit was performed 8 weeks after the baseline examination (visit 2).
      Blood was drawn at each study visit to determine 25-hydroxyvitamin D levels and
      %Tregs. Tregs were characterized as CD4+CD25++ T cells with expression of the
      transcription factor forkhead box P3 and low or absent expression of CD127.
      RESULTS: Forty-six study participants (65% females, mean age +/- SD 31 +/- 8
      years) completed the trial. 25(OH)D levels increased from 23.9 +/- 12.9 ng/ml at
      baseline to 45.9 +/- 14.0 ng/ml at visit 1 and 58.0 +/- 15.1 ng/ml at visit 2.
      %Tregs at baseline were 4.8 +/- 1.4. Compared to baseline levels we noticed a
      significant increase of %Tregs at study visit 1 (5.9 +/- 1.7, P < 0.001) and 2
      (5.6 +/- 1.6, P < 0.001). CONCLUSIONS: Vitamin D supplementation was associated
      with significantly increased %Tregs in apparently healthy individuals. This
      immunomodulatory effect of vitamin D might underlie the associations of vitamin D
      deficiency and autoimmune diseases. Hence, our finding provides a rationale for
      further studies to investigate vitamin D effects on autoimmunological processes.

PMID- 20684176
TI  - Screening, diagnosis, and treatment of renal artery stenosis by percutaneous
      transluminal renal angioplasty with stenting.
AB  - BACKGROUND: Renal artery stenosis is one of the most frequent causes of secondary
      hypertension. Appropriate methods for screening, diagnosis and therapy are
      currently under debate. OBJECTIVES: To evaluate and recommend methods for
      screening and diagnosing renal artery stenosis, and to assess the clinical
      outcomes of renal artery stenting. METHODS: A total of 450 patients undergoing
      non-emergent coronary angiography fulfilled the selection criteria for selective
      renal arteriography; those with severe (luminal narrowing > or = 70%) renal
      artery stenosis underwent percutaneous transluminal renal angioplasty with renal
      artery stenting. RESULTS: Of 166 patients (36.9%) with renal artery stenosis, 41
      (9.1%) had severe stenosis that required renal artery stenting, and 83% had
      ostial renal stenosis. The primary success rate was 100% and there were no
      complications. During the follow-up period, two patients required a second PTRA.
      After stent deployment, significant reductions were observed in systolic and
      diastolic pressures (P < 0.001 and P = 0.01, respectively) and in the number of
      antihypertensive drugs used by the patients (P < 0.001). These reductions were
      sustained during follow-up. Hypertension was cured (systolic blood pressure < 130
      mmHg) in 9 patients (21.4%) and improved in 27 (64.3%). Plasma creatinine did not
      change significantly. CONCLUSIONS: Selective renal angiography is an effective
      diagnostic tool for identifying symptomatic cases of renal artery stenosis in
      patients undergoing coronary angiography. Our finding of a high success rate and
      low complication rate supports the use of primary renal artery stenting in
      symptomatic patients with renal artery stenosis.

PMID- 20684177
TI  - Benefits of high frequency oscillatory ventilation for premature infants.
AB  - BACKGROUND: High frequency oscillatoryventilation based on optimal lung volume
      strategy is one of the accepted modes of ventilatory support for respiratory
      distress syndrome in very low birth weight infants. In 1999 itwas introduced in
      our unit as the primary ventilation modality for RDS. OBJECTIVES: To evaluate if
      the shift to HFOV influenced the outcome of ventilated VLBW infants in the
      neonatal intensive care unit of Carmel Medical Center. METHODS: Data were
      obtained from the medical charts of VLBW infants born at Carmel Medical Center,
      and late mortality data from the Israel Ministry of Internal Affairs records. A
      retrospective analysis and a comparison with a historical control group
      ventilated by the conventional method were performed. RESULTS: A total of 232
      VLBW infants with RDS were mechanically ventilated during the period 1995 to
      2003: 120 were ventilated using HFOV during 1999-2003 and 102 infants using CV
      during 1995-1999. The mean gestational age of survivors was 27.4 +/- 2 weeks in
      the HFOV group and 28.4 +/- 2 in the conventional ventilation group (P = 0.03).
      The sub-sample of infants with birth weight < 1000 g ventilated with HFOV showed
      higher survival rates than the infants in the conventional ventilation group, 53
      vs. 25 (64.6% vs. 44.6%) respectively (P < 0.05). A trend for lower incidence of
      pulmonary interstitial emphysema was observed in the HFOV group. CONCLUSIONS: The
      introduction of HFOV based on optimal lung volume strategy proved to be an
      efficient and safe method of ventilation support for VLBW infants in our unit.

PMID- 20684178
TI  - The association of left atrial volume with exercise capacity in patients with
      chronic severe mitral regurgitation.
AB  - BACKGROUND: Left atrial volume and exercise capacity are strong predictors of
      cardiovascular risk. Decreased exercise capacity is expected when LAV is
      increased due to its association with abnormal left ventricular filling pressure.
      However, LAV enlargement is expected in chronic mitral regurgitation as well.
      OBJECTIVES: To examine the link between LAV and exercise capacity in chronic MR
      and to determine whether larger LAV has indeed better exercise capacity in
      patients with chronic severe degenerative MR and good LV systolic function.
      METHODS: The study included asymptomatic patients with severe chronic
      degenerative MR and normal LV systolic function that underwent stress
      echocardiography. LAV was measured at rest using the biplane Simpson's method and
      indexed to body surface area. The cutoff of good exercise capacity was determined
      at 7 METS. RESULTS: The patient group comprised 52 consecutive patients (age 60
      +/- 14 years, 36 males). Two subgroups (19 vs. 33 patients), age- and gender
      matched, were formed according to LAVi cutoff of 42 ml/m2. Those with higher LAVi
      had lower exercise capacity (P = 0.004) albeit similar MR grade, baseline blood
      pressure, LV function and size. Receiver-operator curve analysis revealed indexed
      LAV value of < or = 42 as 51% sensitive and 88% specific for predicting exercise
      capacity > 7 METS (AUC = 0.7, P = 0.03). In multivariate analysis, age, gender
      and LAVi were identified as independent predictors of exercise capacity.
      CONCLUSIONS: In asymptomatic patients with severe chronic degenerative MR and
      normal LV systolic function, mild enlargement of the left atrium (< or = 42
      ml/m2) is associated with good exercise capacity.

PMID- 20684179
TI  - How to evaluate the child presenting with an apparent life-threatening event?
AB  - BACKGROUND: Infants who have experienced an apparent life-threatening event
      typically undergo an extensive evaluation to rule out serious underlying
      conditions. OBJECTIVES: To evaluate the yield of different tests performed after
      an apparent life-threatening event and to identify high risk groups in which more
      extensive diagnostic tests are required. METHODS: A retrospective study was
      conducted in a children's hospital for a 4 year period and the charts of infants
      who were admitted with an apparent life-threatening event were reviewed. The
      yield for each diagnostic test was established according to the ratio of positive
      results contributing to the diagnosis of the apparent life-threatening event.
      RESULTS: The study included 69 infants between the ages of 1 week and 1 year.
      There were abnormal findings in 36% of the cases. Gastroesophageal reflux was the
      most common diagnosis (60%). In the remaining patients the diagnosis was either
      seizures (12%) or respiratory tract infections (28%). Tests used for the
      diagnosis of cardiac, metabolic and nonrespiratory infections had no yield. A
      positive correlation was found between abnormal test results and abnormal
      physical examination (P = 0.001), an abnormal perinatal history (P = 0.017), and
      age older than 2 months (P = 0.002). CONCLUSIONS: The yield of most of the tests
      performed after an apparent life-threatening event is low, especially in infants
      with a normal perinatal history and physical examination.

PMID- 20684181
TI  - Tubeless percutaneous nephrolithotomy: first 200 cases in Israel.
AB  - BACKGROUND: Tubeless percutaneous nephrolithotomy is defined as PCNL without
      postoperative nephrostomy tubes. It is reported to reduce postoperative pain,
      hospital stay and recovery time. To date the procedure has been reserved for
      selected patients. OBJECTIVES: To assess our initial experience in extending the
      implementation of tubeless PCNL without preoperative patient selection. METHODS:
      All consecutive PCNLs performed during 2004-2008 were evaluated. Tubeless PCNL
      was performed when residual stones, bleeding and extravasation were excluded
      intraoperatively. Staghorn stones, stone burden, supracostal and multiple
      accesses, anatomic anomalies, solitary kidneys and operative time were not
      considered contraindications. We analyzed the clinical data and the choice of
      tubeless PCNL over time. RESULTS: Of 281 PCNLs performed during the study period
      200 (71%) were tubeless. The patients' average age was 53 years (range 28-82
      years), the stone burden was 924 mm2 (400-3150 mm2), operative time was 99
      minutes (45-210 min), complication rate was 14% and immediate stone-free rate
      91%. There were 81 conversions to standard PCNL (29%) due to expected second-look
      (n = 47, 58%), impression of bleeding (n = 21,26%), suspected hydrothorax (n = 7,
      9%) and extravasation (n = 6, 7%). The transfusion rate was 1%. The median
      hospital stay was 1 day (1-15 days) and recovery time 7 days (5-20 days). The
      rate of implementing the tubeless procedure increased steadily along time from
      46% to 83% (P = 0.0001). CONCLUSIONS: Tubeless PCNL can be safely and effectively
      performed based on intraoperative decisions, without preoperative
      contraindications. They are easily accommodated by experienced endourologists and
      provide real advantages.

PMID- 20684180
TI  - Circulating interleukin-10: association with higher mortality in systolic heart
      failure patients with elevated tumor necrosis factor-alpha.
AB  - BACKGROUND: Interleukin-10 is an anti-inflammatory cytokine and consequently is
      considered by many to have a protective role in heart failure, as opposed to the
      notorious tumor necrosis factor-alpha. OBJECTIVES: To test the hypothesis of the
      possible beneficial impact of IL-10 on mortality in systolic heart failure
      patients in relation to their circulating TNFalpha levels. METHODS: We measured
      circulating levels of IL-10 and TNFalpha in 67 ambulatory systolic heart failure
      patients (age 65 +/- 13 years). RESULTS: Mortality was or tended to be higher in
      patients with higher levels (above median level) of circulating TNFalpha (9/23,
      39% vs. 6/44, 14%; P = 0.02) or IL-10 (10/34, 30% vs. 5/33, 15%; P = 0.10).
      However, mortality was highest in the subset of patients with elevation of both
      markers above median (7/16, 44% vs. 8/51, 16%; P = 0.019). Elevation of both
      markers was associated with more than a threefold hazard ratio for mortality (HR
      3.67, 95% confidence interval 1.14-11.78). CONCLUSIONS: Elevated circulating IL
      10 levels in systolic heart failure patients do not have a protective
      counterbalance effect on mortality. Moreover, patients with elevated IL-10 and
      TNFalpha had significantly higher mortality, suggesting that the possible
      interaction in the complex inflammatory and anti-inflammatory network may need
      further study.

PMID- 20684182
TI  - The burden and cost of ambulatory cases of rotavirus gastroenteritis in central
      Israel.
AB  - BACKGROUND: While the burden of rotavirus infection with regard to
      hospitalizations has been extensively investigated, there are sparse data on the
      cost and impact of this infection on the ambulatory part of the health system in
      Israel. OBJECTIVES: To investigate the burden of rotavirus infection on the
      ambulatory system in Israel. METHODS: Infants younger than 3 years examined for
      acute gastrointestinal symptoms in four pediatric clinics had their stool tested
      for rotavirus. The parents were contacted 7-10 days later and questioned about
      the symptoms of illness, medications given, use of diapers, consumption of
      formula, and any loss of parents' workdays. RESULTS: Rotavirus was detected in 71
      of the 145 stool samples tested (49%). A total of 54 parents responded to the
      telephonic survey. Patients' mean age was 15.4 months. Three patients were
      hospitalized due to the illness. The mean duration of fever was 1.7 days. Infants
      with rotavirus gastroenteritis had on average 2.25 days of vomiting and 7.5 days
      of diarrhea. The average number of workdays lost was 2.65 days per RVGE case. The
      cost of the average case of RVGE in Israel is 257 euros; 69.64% of this cost (179
      euros) is due to parental work loss. CONCLUSIONS: Our results indicate that the
      economic impact of the ambulatory cases in Israel is quite significant.

PMID- 20684183
TI  - Ethical dilemmas for physicians in time of war.

PMID- 20684184
TI  - The role of vitamin D in regulating immune responses.

PMID- 20684185
TI  - The use of steroids in epilepsy: time for a reappraisal?

PMID- 20684186
TI  - Capsule endoscopy: no longer limited to the small bowel.
AB  - Capsule endoscopy is the latest evolution in gastrointestinal endoscopy and the
      first to enable complete investigation of the small bowel. Recent new
      developments in the field of capsule endoscopy include the esophageal capsule
      (Pilcam ESO) and the colonic capsule (PillCam Colon). esophageal and colonic
      capsules have two heads with two lenses and cameras. The new capsules have the
      capability of taking more frames from both sides. The indications for the
      esophageal capsule examination are diagnosis and follow-up of Barrett's esophagus
      and esophageal varices. The colonic capsule can be used for colorectal cancer
      screening and for incomplete colonoscopy. Regarding other new technologies,
      continuous quality control is needed for the performance, appropriateness of the
      indications, diagnostic yield, procedure-specific outcome assessment, and cost
      effectiveness.

PMID- 20684187
TI  - Intravenous methylprednisolone pulse therapy in a young girl with intractable
      absence seizures.

PMID- 20684188
TI  - Scurvy in the 21st century.

PMID- 20684189
TI  - Indolent systemic mastocytosis.

PMID- 20684190
TI  - Infantile pyknocytosis: a rare form of neonatal anemia.

PMID- 20684191
TI  - Massive legs and a massive thrombus.

PMID- 20684192
TI  - Computed tomography scan in necrotizing granulomatosis.

PMID- 20684193
TI  - [The mission of surgeon].

PMID- 20684194
TI  - [Sharing the roles with co-medical staff in the surgical field--present and
      future].

PMID- 20684195
TI  - [Surgeons' hope: expanding the professional role of co-medical staff and
      introducing the nurse practitioner/physician assistant and team approach to the
      healthcare system].
AB  - The healthcare system surrounding surgeons is collapsing due to Japan's policy of
      limiting health expenditure, market fundamentalism, shortage of healthcare
      providers, unfavorable working environment for surgeons, increasing risk of
      malpractice suits, and decreasing number of those who desire to pursue the
      surgery specialty. In the USA, nonphysician and mid-level clinicians such as
      nurse practitioners (NPs) and physician assistants (PAs) have been working since
      the 1960s, and the team approach to medicine which benefits patients is
      functioning well. One strategy to avoid the collapse of the Japanese surgical
      healthcare system is introducing the NP/PA system. The division of labor in
      medicine can provide high-quality, safe healthcare and increase the confidence of
      the public by contributing to: reduced postoperative complications; increased
      patient satisfaction; decreased length of postoperative hospital stay: and
      economic benefits. We have requested that the Ministry of Health, Labor and
      Welfare establish a Japanese NP/PA system to care for patients more efficiently
      perioperatively. The ministry has decided to launch a trial profession called
      "tokutei (specifically qualified) nurse" in February 2010. These nurses will be
      trained and educated at the Master's degree level and allowed to practice several
      predetermined skill sets under physician supervision. We hope that all healthcare
      providers will assist in transforming the tokutei nurse system into a Japanese
      NP/PA system.

PMID- 20684196
TI  - [Burden sharing with co-medical personnel in the surgical area: present and
      future situations. The clinical engineer's position].
AB  - It has been 22 years since clinical engineers first made their appearance as
      experts in medical equipment used to save patients' lives. At that time, legal
      revisions, ministerial ordinances, and regulations were established, with the
      final step awaiting a change in the medical environment. The pressing problem of
      a serious shortage of physicians is now apparent. The role of clinical engineers
      can be seen as providing one solution to this problem from the viewpoint of team
      medical treatment. A study is currently underway to determine how clinical
      engineers, who are co-medical members of the team, might also be expected to
      contribute a type of new militant power" to the medical field. In current
      surgical procedures, clinical engineers are necessary to operate various high
      risk therapeutic equipment such as therapeutic surgical and life support devices.
      Clinical engineers work not only in the control of life support devices but also
      in expanded fields in perioperative care. A revision of the clinical engineer's
      role in perioperative care and work guidelines is needed so that their
      fundamental strengths can promote such goals as improved medical safety and a
      reduction in the burden on physicians and other medical personnel.

PMID- 20684197
TI  - [The role of multi-disciplinary team in the surgical area--at present and in
      future].
AB  - This article describes four particular tasks of nursing profession and identifies
      the contribution of nurses within a multi-professional team in the surgical area.
      The four tasks involve; triage nursing in Emergency Room; allocation of surgical
      beds; provision of patients' information on a course of surgical treatment prior
      to hospital admission; and participation in Diagnosis Related Group (DRG). Being
      responsible for each of these tasks, the nurses play a significant role as
      mediators between patients and health professionals as well as between the health
      professionals in order to respond to their patients' needs. This contributes to
      alleviation of suffering through the diagnosis and surgical treatment, leading to
      the best ways to recover from major trauma the patients had. In recent years,
      expanding nursing responsibilities for decision-making in patients' care has been
      in discussion. However, it is clear that with certain levels of education and
      practice, nursing profession is able to fill the important roles within the multi
      professional team in the surgical area.

PMID- 20684198
TI  - [Nurse practitioners in acute care settings in the United States].
AB  - Japan is currently at a historic moment to recognize the significance of the team
      approach in medicine. There is a mismatch between the supply of physicians and
      demand for expert care that our patients expect and deserve. The acute care
      setting including surgery is considering adopting non-physician professionals
      such as nurse practitioners (NPs) in order to deliver a high quality of care. The
      NPs in acute care setting have evolved in the United States to meet the medical
      needs of the society over the last four decades. With the increased complexity of
      the needs of the patients in Japan, a creative innovation in the care delivery
      system is required. The use of the NPs in the acute care began in the neonatal
      intensive care unit in the early 70's as described in the author's previous
      article. The adult critical care realm embraced the collaborative model starting
      in the 90's and opened its doors widely as resident duty hours were reduced for
      the patient safety concerns. This article describes the wide variety of settings
      in which acute care NPs are found in the US today. The current model of
      collaborative practice owes its development and success to the committed
      physicians and nurses who crossed each other's boundaries for the sake of the
      patients decades ago.

PMID- 20684199
TI  - [Surgical PA's role, influence, effectiveness, and utilization outlook].
AB  - Physician Assistants (PA) are licensed medical practitioners in the United States
      who practice in the various specialties. According to 2008 PA Census,
      approximately one quarter of the PA's practice in the surgery or other surgical
      sub-specialties. In this article, surgical PA's role, influence, and
      effectiveness as well as outlook of surgical PA utilization will be examined.

PMID- 20684200
TI  - [The role of co-medical staff in surgical treatment from the viewpoint of
      respiratory therapists].
AB  - Appropriate perioperative assessment of respiratory function and subsequent
      respiratory therapy are mandatory to reduce postoperative pulmonary complications
      and restore pulmonary reserve function after surgery. Preoperative instructions
      on smoking cessation, expectoration of sputum or coughing, and respiratory
      training are also useful to shorten hospital admissions. A respiratory support
      team (RST) composed of physicians and special co-medical staff is necessary to
      achieve the optimal results for patients. Certified respiratory therapists
      approved by the Joint Committee on Respiratory Therapy have a particularly
      important role in performing respiratory therapy. In the near future,
      interdisciplinary organization and cooperation between various medical staff will
      be necessary for the smooth management of RSTs in medical institutions.

PMID- 20684201
TI  - [Sex reassignment surgery in female to male transsexuals].

PMID- 20684202
TI  - [What we can learn from a case of medical malpractice--death due to complications
      after preventive craniotomy for unruptured aneurysms].

PMID- 20684203
TI  - [Thoracoscopic repair of esophageal atresia].

PMID- 20684204
TI  - [Importance of expanded role of non-physician healthcare provider in surgical
      practice--from analysis results of work contents obtained from workweek-time
      study of JSS members].

PMID- 20684205
TI  - [How long do surgeons work a week?].

PMID- 20684206
TI  - [Present status of pediatric living-donor liver transplantation in National
      Center for Child Health and Development].
AB  - PURPOSE: We reviewed our initial experience of pediatric living-donor liver
      transplantation (LDLT) in National Center for Child Health and Development and
      report the results herein. SUBJECTS AND METHODS: We have done 103 cases of LDLT
      during November 2005 through September 2009 in National Center for Child Health
      and Development. Variables including indication of liver
      transplantation/infectious/immunological outcome were reviewed. RESULTS: The
      indication for liver transplantation was cholestatic liver disease in 43.76%,
      followed by metabolic liver disease 24.3% and acute liver failure 18.5%. The mean
      age of recipient was 3.6 +/- 4.2 years and body weight was 14.4 +/- 11.1kg.
      Immunosuppression consisted of tacrolimus and low-dose steroids. The incidence of
      acute cellular rejection was 33.3%. The graft and patient survival were 92.2%.
      CONCLUSION: Satisfactory result can be achieved on LDLT program in National
      Center for Child Health and Development. The follow-up period was too short to
      make definitive conclusion, however, long-term observation may be necessary to
      collect sufficient data for the establishment of the treatment modality.

PMID- 20684207
TI  - [The influence of pathological diagnosis on outcome in patients with idiopathic
      pulmonary fibrosis].
AB  - The definitive diagnosis of idiopathic pulmonary fibrosis (IPF) requires a
      pathologic pattern of usual interstitial pneumonia (UIP). However, it is not
      clear that whether there is a difference in outcome between patients with IPF
      diagnosed by clinical findings, and those diagnosed by pathological findings. We
      investigated differences in survival between patients diagnosed with IPF based on
      clinical findings, and patients who underwent surgical biopsy for a pathological
      diagnosis of IPF/UIP based on findings showing a UIP pattern. Sixty-one patients
      who received a clinical diagnosis of IPF were selected by random sampling. Fifty
      nine patients underwent open lung biopsy or video assisted thoracoscopic biopsy
      and receive a pathological diagnosis of IPF/UIP. At diagnosis, 23 clinical
      features were identified and the hazard ratio of pathological diagnosis was
      estimated using the Cox proportional hazard model adjusted for those features
      that differed between the two groups. The adjusted hazard ratio of pathological
      diagnosis, taking these factors into account, was 1.09 (95% confidence interval,
      0.42 to 2.80, p = 0.861) to about 1.0. Therefore, it is reasonable to diagnose
      IPF based on clinical findings from the perspective of outcome.

PMID- 20684208
TI  - [The relationship between the duration and severity of asthma].
AB  - BACKGROUND: The relationship between the duration and severity of asthma has not
      been comprehensively investigated. METHODS: We examined the relationship between
      duration of asthma and asthma severity among 4776 patients with asthma: 608 with
      childhood-onset persistent asthma (12.7%), 187 with adolescent-onset asthma
      (3.9%), and 3981 with adult-onset asthma (83.4%). The assessment of asthma
      severity was based on the Japanese Guidelines for The Diagnosis and Treatment of
      Allergic Diseases, 2007 (JGL 2007). RESULTS: Asthma severity was assessed at 2
      years, 3 to 10 years. 11 to 20 years, and 21 years or longer after disease onset.
      Disease severity significantly increased with greater asthma duration (p<0.001).
      This relationship was not affected by serum total IgE concentration (<300 IU/ml
      vs > or = 300 IU/ml), smoking status, house dust mite-specific serum IgE antibody
      level, or gender. CONCLUSION: Our findings suggest that bronchial asthma is a
      disease that worsens over time.

PMID- 20684209
TI  - [The role of positron emission tomography in the detection of incidental
      gastrointestinal tract lesions in patients examined for lung cancer].
AB  - The purpose of this study was to clarify the clinical characteristics of lung
      cancer patients with abnormal accumulation in the gastrointestinal tract by
      fluoro-2-deoxyglucose positron emission tomography (PET). Of the 968 consecutive
      patients with primary lung cancer who underwent PET from October 2005 through
      September 2009, 26 patients had local abnormal accumulation in the
      gastrointestinal tract. We retrospectively compared the localization of abnormal
      accumulation in the gastrointestinal tract, standardized uptake value (SUV) max
      (1 hour), and the final clinical diagnosis. The site of abnormal accumulation was
      the esophagus in 1 case, the stomach in 8 and the small intestine to large
      intestine in 17. In 15 out of 26 (57%) cases with true PET positive results,
      there was esophageal cancer in 1 case, gastric cancer in 2, gastrointestinal
      stromal tumor in 1, colon cancer in 8, and 1 each of metastasis to the stomach,
      small intestine and large intestine from lung cancer. In 11 cases with false PET
      positive results, there was a stomach polyp in 1 case, gastritis in 3, colon
      polyp in 1, diverticulitis in 1 and normal physiologic accumulation in 5. There
      were no differences in mean SUV max among malignant lesions, benign lesions, and
      normal physiologic accumulation. We should perform endoscopy of the digestive
      tract to detect malignant lesions with high incidence rates when PET shows
      localalized abnormal accumulation in the gastrointestinal, tract in patients with
      lung cancer.

PMID- 20684210
TI  - [A case of intubation granuloma treated with steroid inhalation].
AB  - A 36-year-old woman was given a diagnosis of hemophagocytic syndrome associated
      with systemic lupus erythematosus, and was treated with high-dose
      methylprednisolone and etoposide. She needed endotracheal intubation for
      mechanical ventilation because of respiratory failure. She developed hoarseness
      and stridor 69 days after extubation. A pedunculated mass under her glottis was
      observed by the laryngoscopy. Development of a laryngeal granuloma due to long
      term contact with the endotracheal tube was considered, although she was
      continuously given oral prednisolone (22.5 mg/day) even after extubation. She was
      treated with inhalation of fluticasone propionate and her symptoms, e.g.
      hoarseness, decreased. Disappearance of the polypoid lesion was seen on day 26. A
      laryngeal granuloma due to intubation developed, even with the systemic
      administration of steroids; but it was successfully treated with steroid
      inhalation.

PMID- 20684211
TI  - [A case of repeated bilateral pneumothorax associated with upper lobe predominant
      fibrosis in an aluminum processing worker].
AB  - A 39-year-old man, who had been working in an aluminum processing industry for 18
      years, visited our hospital for right chest pain on March 2, 2007. A relapse of
      right pneumothorax was found, and he was hospitalized. As the pneumothorax did
      not improve with conservative treatment, video-assisted thoracoscopic biopsy and
      suturing of the right upper lobe were successfully performed. The pulmonary
      parenchyma had collapsed, there was pulmonary fibrosis, and lymphocytes had
      gathered in follicules. Based on elemental analysis results, we diagnosed
      aluminum lung. It was thought that overexpansion of the lower lobe with the
      predominant upper lobe fibrosis was caused by the aluminum deposition. We judged
      his condition to be serious and we started treatment with 25 mg/day prednisolone
      (PSL), and 120 mg/day cyclosporine (CyA). At the time of writing, he is an
      outpatient, and is being monitored on a regimen of 5 mg/day PSL and 160 mg/day
      CyA without any progression of pulmonary fibrosis or relapse of pneumothorax.

PMID- 20684212
TI  - [A case of primary small intestinal malignant lymphoma found based on multiple
      pulmonary nodules with cavitation].
AB  - A 72-year-old man complained of dyspnea and epigastric pain. He was admitted to
      our hospital with progressive dyspnea and abnormal chest radiograph findings.
      Chest CT scan on admission showed multiple nodular shadows with and without air
      bronchograms, vessels or cavitation. Transbronchial and percutaneous lung biopsy
      specimens demonstrated poorly differentiated carcinoma. Pulmonary metastases were
      suspected, but their primary origin was unknown. Chest and abdominal CT scans on
      the 18th hospital day showed a giant tumor of the small intestine and rapid
      progression of the pulmonary tumor, forming cavitation. The patient's condition
      worsened, and he died on the 51st hospital day. At autopsy, a final diagnosis of
      T-cell lymphoma of the small intestine and pulmonary metastases was obtained.
      This is a rare case which was found primarily based on the characteristic
      radiologic features of pulmonary metastases.

PMID- 20684213
TI  - [Pulmonary Langerhans cell histiocytosis in identical twins].
AB  - Case 1 was a 22-year-old younger sister of identical twins who had smoked 10
      cigarettes per day for 4 years since she was 18. She was admitted to our hospital
      due to dyspnea on exertion, dry cough and bilateral diffuse reticulonodular
      infiltrates on chest computed tomography (CT). Histological findings of
      transbronchial lung biopsy demonstrated nodular lesions consisting of spindle
      shaped mononuclear cells. Immunohistochemical studies revealed that the cytoplasm
      of these mononuclear cells showed positive reactions to CD1a. Based on these
      findings, she was given a diagnosis of pulmonary Langerhans cell histiocytosis
      (LCH). She reduced the number of cigarettes smoked to 1 cigarette per week. After
      6 months, her respiratory symptoms and radiographic abnormalities had improved.
      Case 2 was the elder twin sister of case 1. She had smoked 5 cigarettes per day
      for 4 years since she was 18. She presented no respiratory symptoms. However, as
      the diagnosis in case 1 was LCH, a chest CT was taken which revealed 3 small
      nodular lesions. After six months, there were no significant changes on chest CT.
      At the time of writing, she is 23-years-old and continues to smoke, however, has
      no respiratory symptoms.

PMID- 20684214
TI  - [Large cell neuroendocrine carcinoma of the mediastinum].
AB  - We describe a rare case of primary mediastinal large cell neuroendocrine
      carcinoma (LCNEC) with brain metastases. A 65-year-old man presented with a
      mediastinal abnormal shadow on chest radiography. A computed tomography-guided
      needle biopsy of the mediastinal tumor revealed malignant cells. After biopsy,
      dyspnea, leg weakness and a waddling gait rapidly developed. Magnetic resonance
      imaging of the brain revealed three masses with ring enhancements. His pro-GRP
      value was 95.5 pg/ml. Since the cerebellar tumor extended to the brain stem, it
      was removed surgically. The brain tumor demonstrated LCNEC. He received systemic
      chemotherapy of cisplatin and irinotecan, because his leg weakness and waddling
      gait had improved markedly after surgery followed by whole brain irradiation.

PMID- 20684215
TI  - [A case of localized malignant pleural mesothelioma].
AB  - A 74-year-old man was referred to our hospital for examination of an abnormal
      chest shadow. A chest computed tomography (CT) scan revealed a 5-cm mass attached
      to the pleura involving the right upper lobe, and a nodule in the right middle
      lobe. Transbronchial lung biopsy was performed twice, but no definitive diagnosis
      was achieved. 18-fluorodeoxyglucose positron emission tomography showed abnormal
      uptake in the chest lesion. Chemotherapy was initiated for advanced-stage lung
      cancer, but was not effective. Histopathologic and immunohistochemical
      examinations after CT-guided needle biopsy revealed malignant mesothelioma. The
      tumor cells were positive for calretinin and thrombomodulin, and negative for
      CEA, TTF-1, and SP-A. There was local tumor invasion and metastasis in the lung
      and brain, without diffuse pleural spread. This is a rare and important case of
      localized malignant mesothelioma pathologically confirmed by biopsy.

PMID- 20684216
TI  - [A case of pulmonary alveolar proteinosis that showed solitary ground-glass
      opacity in the subpleural area].
AB  - A 58-year-old man visited our department regarding a growing ground-glass opacity
      (GGO) on chest CT. He underwent video-assisted thoracic surgery, because a
      malignancy such as bronchioloalveolar adenocarcinoma was suspected. However,
      histopathologic examination revealed pulmonary alveolar proteinosis (PAP). A
      chest X-ray film of PAP usually shows bilateral interstitial and/or alveolar
      shadows in a "butterfly pattern", while chest CT usually shows thickened
      interlobular septa and intralobular structures, referred to as a "crazy-paving
      appearance". The present case presented solitary localized GGO growing in a
      subpleural area which was thought to be a rare type of early PAP.

PMID- 20684217
TI  - [A suspected case of acute respiratory failure caused by ritodrine
      hydrochloride].
AB  - A 36-year-old woman was admitted to the obstetric department because of possible
      premature labor of twins at 35 weeks. She had been treated by ritodrine
      hydrochloride, a tocolytic agent, for 1 week, and delivered healthy twins by
      cesarean operation. After the operation, she suddenly complained of dyspnea with
      associated hypoxemia and was admitted to our hospital. She presented with
      hypoxemia and was given a diagnosis of pulmonary edema. She was given a diuretic
      with ventilator therapy, and improved rapidly. However, an echocardiogram showed
      continuing left ventricular systolic dysfunction after 3 months. From these
      results, this case was suspected to be pulmonary edema due to ritodrin after
      myocardial failure, including peripartum cardiomyopathy.

PMID- 20684218
TI  - [A case of IgG4-positive multi-organ lymphoproliferative syndrome associated with
      Kimura disease].
AB  - A 46-year-old man, who had been treated for Kimura disease, was found to have
      abnormal findings on a chest radiograph. Chest CT showed a mass shadow in the
      right lower lobe. Histological findings of a transbronchial biopsy specimen
      showed inflammatory cells infiltrating the alveolar septum. Inflammatory cells
      consisted of plasma cells, lymphocytes and eosinophils. He had had sustained
      eosinophilia and elevation of IgE for 8 years, and his serum IgG and IgG4 (3480
      mg/dl) levels were elevated. Contrast-enhanced computed tomography showed
      multiple low density areas in both kidneys. Since immunohistochemical staining of
      the lung specimens revealed infiltration of IgG4-positive plasma cells (IgG4
      positive/IgG-positive plasma cells=35%), we diagnosed IgG4-positive multiorgan
      lymphoproliferative syndrome. The mass shadow had disappeared after treatment
      with celestamine (0.25 mg betamethasone and 2 mg dexchlorpheniramine) for Kimura
      disease, but another solid consolidation appeared in the contralateral lower lobe
      5 months later. After the steroid dosage was increased, the consolidation
      improved. To the best of our knowledge, this case is the first report of IgG4
      positive multi-organ lymphoproliferative syndrome associated with Kimura disease.

PMID- 20684219
TI  - [A case of Henoch-Schonlein purpura which was difficult to distinguish from a
      skin rash associated with gefitinib].
AB  - A 52-year-old woman with advanced non-small cell lung cancer was admitted to our
      hospital with melena and palpable purpura which appeared on her lower legs. She
      had been taking gefitinib for about 2 months before admission. A skin biopsy
      revealed leukocytoclastic vasculitis in the superficial dermis and
      immunofluorescence also showed the presence of C3 depositions within the blood
      vessel walls, which led to a diagnosis of Henoch-Schonlein purpura. The purpura
      gradually improved with topical steroids and bed rest; however, gefitinib had to
      be discontinued because of a growing papulopustular rash with intense itching,
      and as a result of the discontinuation, both types of skin lesions resolved. Two
      months later, she resumed gefitinib treatment since her level of CEA began to
      rise. Even though the papulopustular rash developed after the readministration of
      gefitinib, there had been no evidence of Henoch-Schonlein purpura recurrence
      during 2.5 years follow-up. It has been reported that adult onset Henoch
      Schonlein purpura is often associated with malignancy. This case, however,
      suggests that not only drug eruption but also paraneoplastic vasculitis should be
      considered in the differential diagnosis of palpable purpura in patients with non
      small cell lung cancer receiving treatment with gefitinib.

PMID- 20684220
TI  - [A case of metastatic pulmonary cancer from renal cell carcinoma masquerading as
      pulmonary vein varix].
AB  - A 66-year-old woman underwent nephrectomy to treat renal cell carcinoma 5 years
      previously. Enhanced CT to locate the tumor revealed a lesion very close to the
      right upper pulmonary vein. Six months later, the nodule grew to 14mm in maximum
      dimension and it seemed to be a varix of the right upper pulmonary vein on 3D-CT.
      However, pulmonary artery angiography (PAG) denied this possibility. PET-CT
      revealed the nodule to be positive for FDG uptake (maxSUV 2.7 in the early phase
      and 2.2 in the late phase), suggesting that it contained solid tissue with
      malignant characteristics. Eventually, right upper lobectomy was performed. The
      nodule was a metastatic renal cell carcinoma with extremely abundant vascular
      components. This conspicuous feature of the tumor appeared to mimic a pulmonary
      vein varix on enhanced CT scan and 3D angiogram.

PMID- 20684221
TI  - [The utility of the fraction of exhaled nitric oxide for diagnosing asthma is
      decreased in non-atopic smokers].

PMID- 20684222
TI  - [Interpretation of lung age].

PMID- 20684223
TI  - [The registry report of Japanese lung transplantation--2009].
AB  - OBJECTIVE: To scrutinize the status of lung transplantation in Japan, the
      Japanese Society of Lung and Heart-Lung Transplantation started to collect and
      present registry data from 2005. This is the 5th official registry report of
      Japanese lung transplantation. DESIGN AND METHODS: The data of cadaveric lung
      transplantation and living-donor lobar transplantation performed by the end of
      2008 were registered to the database and analyzed with respect to the number of
      transplants, recipient survival rates, recipient functional and working status,
      and cause of death after transplantation. Survival rates were calculated by the
      Kaplan-Meier method. RESULTS: Fifty-three (30 single and 23 bilateral) cadaveric
      lung transplantations and 77 living-donor lobar transplantations were performed
      by the end of 2008. Five-year survival rates of cadaveric single and bilateral
      lung transplantations were 61.9% and 62.5%, respectively, which were both
      superior to those in the International Registry (47.1% and 55.0%, respectively).
      Five-year and 10-year survival rates of living-donor lobar transplantation were
      excellent at 79.9% and 77.0%, respectively. The functional status of >80% of
      recipients was restored to Hugh-Jones I or II after transplantation. Infection
      was the leading cause of death after lung transplantation. CONCLUSION: The
      results of Japanese lung transplantation are so far satisfactory although we
      should note the small number of lung transplant cases in Japan. The Japanese
      Society of Lung and Heart-Lung Transplantation will continue to present the
      annual report of Japanese lung transplantation.

PMID- 20684224
TI  - [Na+,K(+)-ATPase activity in polarized cells].
AB  - The novel views on fundamental role of Na+,K(+)-ATPase in regulation of the
      polarized morphology of the epithelial cells, enzyme involvement in signal
      transduction, assembly of intermolecular signaling complexes have been reviewed.
      The modern state of researches are considered in detail, including: sorting
      specificity in polarized cells, Na+,K(+)-ATPase involvement in epithelial cell
      interactions, enzyme arrangement in combined structural and functional ensemble
      with adhesion and cytoskeleton proteins, their coordinated exp ression. The
      mechanisms of the Na+,K(+)-ATPase association with its molecular partners and the
      role of specific domains, motives and binding sites are analysed. The available
      data, including own researches indicate the Na+,K(+)-ATPase involvement in
      certain pathologies that develop with aberration of polarized epithelial
      phenotype, malignant growth in particular.

PMID- 20684225
TI  - [Spatial structure of the calixarene-aminophosphonic acids is important for their
      inhibition of the Na+,K(+)-ATPase activity in plasma membrane of smooth muscle
      cells].
AB  - It was found that calixarene C-107 (5,17-diamino(2-pyridyl)methylphosphono-11,23
      di-tret-butyl-26,28-dihydroxy-25,27-dipropoxycalix[4]arene) could effectively
      reduce Na+,K(+)-ATPase activity of the myometrium cell plasmatic membranes (the
      value of the apparent constant of inhibition I0.5 was 33 +/- 4 nM) while it
      practically did not influence the "basal" Mg2(+)-ATPase activity of the same
      membrane. In comparative experiments, we have shown that the model calixarene C
      150--the calixarene "scaffold" (26,28-dihydroxy-25,27-dipropoxycalix[4]arene),
      and the model compound M-3 (4-hydroxyaniline(2-pyridine)methylphosphonic acid)--a
      fragment of the calixarene C-107, had practically no influence on the enzymatic
      activities of Na+,K(+)-ATPase and Mg(2+)-ATPase over a wide range of
      concentrations. Hence, the influence of calixarene C-107 on Na+,K(+)-ATPase
      activity was caused by the joint action of two aminophosphonic substituents on
      the upper rim of the calixarene bowl. The isomer of calixarene C-107--calixarene
      C-160 (5,11-diamino(2-pyridyl)methylphosphono-17,23-di-tret-butyl-26,28-dihydroxy
      25,27-dipropoxycalix[4]arene) also did not influence the Na+,K(+)-ATPase and
      Mg(2+)-ATPase activities of plasmatic membrane of myometrium cells. We carried
      out molecular modeling of calixarenes C-107 and C-160 and showed differences in
      interatomic distance between aminophosphonic substituents of mentioned
      calixarenes. We came to the conclusion that spatial structure of calixarene C
      107, namely localization of two aminophosphonic substituents in 5,17 position of
      the upper rim of this calixarene, is crucial for inhibition of Na+,K(+)-ATPase
      activity. Using laser correlation spectroscopy it was found that the 100 microM
      solution of calixarene C-107 and 2.5% DMSO had microparticles with size range
      from 100 nm to 10 microm. Plasma membrane vesicles had average hydrodynamic
      diameter 401 +/- 17 nm, but after interaction of these vesicles with calixarene C
      107 we have registered the creation of some particles with sizes greater than 10
      microm. Therefore membrane vesicles agglutinated to each other and/ or to
      calixarene microparticles.

PMID- 20684226
TI  - [Existence of two different active sites on thiamine binding protein in plasma
      membranes of synaptosomes].
AB  - The current work is aimed at understanding the structure and functionality of
      thiamine binding protein (TBP) in neural cells plasma membranes. The influence of
      thiamine triphosphate on thiamine binding by TBP in synaptic plasma membranes
      (SPM) isolated from the rat brain was investigated. It was shown that thiamine
      triphosphate inhibits thiamine binding activity of SPM in concurrent manner (K(i)
      = 1.0 +/- 0.3 microM). At the same time thiamine had no effect on thiamine
      triphosphatase (ThTPase) activity at the concentration range 0.5-20 microM.
      Otherwise, ThTPase activation with the maximum at the concentration about 2.5
      microM was observed. Further, the influence of classic thiamine antagonists
      (amprolium, oxythiamine and pyrithiamine) on both biological activities of TBP in
      SPM was studied. The IC50 value for inhibition of thiamine binding on SPM by
      amprolium comprised 50 +/- 4.0 microM. Still, this antagonist had no effect on
      ThTPase activity. For the oxythiamine inhibition of both TBP activities was
      detected. The values of IC50 were 125 +/- 28 and 1000 +/- 95 microM for thiamine
      binding and ThTPase activity, respectively. The values of IC50 for thiamine
      binding and ThTPase activity inhibition differed by more than one order of
      magnitude and comprised 2.2 +/- 0.2 and 43 +/- 9 microM, respectively. The
      obtained data indicate that the active sites on SPM responsible for thiamine
      binding and ThTPase activity have different sensitivity to thiamine antagonists.
      Our results allow us to suppose that different active protein sites are
      responsible for the specific binding and for thiamine phosphates hydrolysis by
      TBP of synaptic membranes.

PMID- 20684227
TI  - [Effect of 3-decyloxycarbonylmethyl-4-methyl-5-(beta-hydroxyethyl)thiazole
      chloride on nystatin-created K(+)-current across bilayer lipid membrane].
AB  - The application of 0.1 mM of vitamin B1 (thiamine) structural analogue, 3
      decyloxycarbonylmethyl-4-methyl-5-(beta-hydroxyethyl)thiazole chloride (DMHT)
      from the cis-side of cholesterol-containing phospholipid bilayer membrane in
      symmetric solution of 100 mM KCl reversibly reduced the conductance of nystatin
      channels, reconstituted from the same side of membrane, by 67 +/- 3%. The
      conductance of nystatin channels applied to the cis-side of bilayer membrane
      remained unaffected, when DMHT was introduced separately to the opposite trans
      side of modified membrane. The kinetics of nystatin channels inhibition with DMHT
      showed no cooperativity allowing to expect that negatively charged ionogenic
      groups of these channels formed one DMHT binding site per channel. Relatively
      high pK of binding with nystatin channels (5,17) suggests that this site provides
      specific interaction with DMHT.

PMID- 20684228
TI  - [Registration of K(+)-equilibrium potential in myometrium cell plasma membrane
      and study of its modulation of NO(x) and H2O2, using flow cytometry method].
AB  - Prospects of the use of flow cytometry analysis for investigation of forming K(+)
      equilibrium membrane potential on the experimental model of myometrium plasma
      membrane vesicles in the presence of valinomycine using potential-sensitive probe
      of DiOC6(3). Transmembrane potential magnitude corresponds to magnitude by
      Nernst's equation. H2O2 and NO2-, probably, increase permeability of membrane for
      K+ and result in potential dissipation. Given effect is not shown for sodium
      nitroprusside. The obtained results confirm an assumption as to enhancing the
      passive transport for K+ through sarcolemma under the action of these substances,
      that can lead to membrane repolarisation and decline of the level of its
      excitability.

PMID- 20684229
TI  - [The effect of blood serum polyreactive immunoglobulins on serum antibody
      affinity determination].
AB  - The presence of polyreactive immunoglobulins in sera may substantially influence
      on the accuracy of antibody affinity determination. In order to obtain precise
      values of antibody affinity one should apply one of two following ways. First,
      one should block polyreactive immunoglobulins with high concentration of Twin 20
      and high concentration of any antigen which does not interact with studying
      antibody. After this antibody affinity may be determined by traditional methods.
      Another way is the application of the method suggested by us earlier, which allow
      determining affinity of two antibodies in a mixture and the relation of their
      concentrations.

PMID- 20684230
TI  - [Interrelation between antioxidant hepatoprotective action of some derivatives of
      monochromanes and trimethylphenols and energy structural quantum-chemical
      parameters].
AB  - Energy and structural parameters of monochromanes and trimethylphenols
      derivatives have been chracterized through the employment of semiempirical
      methods of quantum chemistry. The correlation has been proved between
      antiradical, hepatoprotective properties of these compounds and energy and
      structural of their molecules that confirms the presence of relation between
      structure activity and electron-donor properties of the investigated
      monochromanes and trimethylphenols.

PMID- 20684231
TI  - [Effect of continuous and impulsive ultrasound on actomyosin superprecipitation
      reaction from rabbit skeletal muscles].
AB  - A comparative study of the effect of continuous and impulsive (2 ms) ultrasound
      regimes on actomyosin superprecipitation reaction of the rabbit skeletal muscles
      was carried out. From the obtained kinetic curves the value of superprecipitation
      (D(m) - D(00)), time t1/2, which required to achieve a half its value was
      determined, and the normalized maximal rate of this reaction V(n) was calculated
      as well. It is shown that continuous ultrasound with intensities 0.7 W/cm2 and
      impulsive ultrasound--of 0.4 W/cm2 produced the most pronounced effect (value of
      superprecipitation and V(n) were maximal). The actomyosin superprecipitation
      value under continuous and impulsive ultrasound with intensity 1 W/cm2 relative
      to control and all other applied intensities was most decreased. It is caused
      perhaps thermal influence of the ultrasound. Thus the obtained data give every
      reason to assume, that impulsive ultrasound causes changes of adaptive character
      in actomyosin because the interrupted regime of the ultrasound signal.

PMID- 20684232
TI  - [Initial analysis of the results of the genome-wide search for the genes
      responsive to interferon alpha].
AB  - The paper is focused on the primary analysis of the potential genes of primary
      response to IFNalpha, predicted by the program COTRASIF elaborated in our
      laboratory. Two web-instruments FatiGO and GOTM were applied for this purpose;
      the literature search was carried out using IHOP; genes were classified according
      to the conceptual diagram "Gene Ontology" (GO) and were ranked according to their
      first priority for the experimental validation. On the basis of conducted
      analysis 162 genes of potential primary response to IFNalpha were subdivided into
      two groups--61 genes, for which the experimental data of their responsibility to
      IFNalpha were found and 101 genes for which such data are absent. We have
      performed the functional analysis of the "unknown" genes according to GO. The
      enriched category "Synapse part" encountering three genes of Rattus norvegicus:
      PRKCA-binding of protein, NMDAR-L and GABAA--receptor subunit alpha-2 were
      revealed. Among 162 genes the enriched category "Immune response" was detected
      with Mbl1 gene, which is reckoned among "unknown" genes. The four designated
      genes are chosen as the candidates for the prior validation.

PMID- 20684233
TI  - [Expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-2 mRNA and
      its alternative splice variants in rats with experimental diabetes mellitus].
AB  - We studied the expression mRNA of 6-phosphofructo-2-kinase/fructose-2,6
      bisphosphatase-2 (PFKFB-2) in the rat lung and kidney in experimental diabetes
      mellitus. For investigation we select two isoforms of PFKFB-2 with different C
      terminus. The level of the expression of both PFKFB-2 mRNA isoforms is decreased
      in the kidney and lung in rats with experimental diabetes mellitus respect to the
      control animals. Moreover, four new alternative splice variants of PFKFB-2 mRNA
      were identified in the rat kidney. These splice variants of PFKFB-2 mRNA have
      different inserts and/or deletions in 6-phosphofructo-2-kinase as well as in
      fructose-2,6-bisphosphatase part of PFKFB-2. Three alternative splice variants
      cannot encode active 6-phosphofructo-2-kinase as a result of deletion of two
      catalytic domains (E and F). They encode fructose-2,6-bisphosphatase. It was
      shown that these alternative splice variants express in the kidney and lung and
      that this expression changes in rats with experimental diabetes mellitus with
      respect to the control animals. The results of this investigation clearly
      demonstrated that diabetes mellitus significantly affects the expression and
      alternative splicing of PFKFB-2 in the kidney and lungs and showed the complexity
      of regulatory mechanisms of glucose metabolism in this disease.

PMID- 20684234
TI  - [Changes in genes expression caused by overexpression of the transcription factor
      ZXDC in embryonic kidney cell line HEK293].
AB  - The transcription factor ZXDC, a member of ZXD protein family, forms
      transcriptionally active complex with ZXDA and participates in the regulation of
      MHCII gene expression. In this work we investigate the expression of a large
      group of genes in kidney embry cell of line HEK293 with overexpression of
      transcription factor ZXDC for identification of genes, which transcription is
      controlled by this transcription factor. We have shown that overexpression of the
      transcription factor ZXDC in kidney embryo cell of HEK293 line significantly
      changes the level of expression of large group of genes, which control the
      behavior of different cell processes, in particular cell cycle, cell
      proliferation and differentiation. The expression of most of these genes is
      significantly increased in the kidney cell line HEK293 with overexpression of
      transcription factor ZXDC, in particular EGR2, BDNF, CDKN1C and IL5Ra genes. Our
      results clearly demonstrated that transcription factor ZXDC plays a significant
      role in the regulation of expression of a large group of genes, which control
      important cell processes.

PMID- 20684235
TI  - [Protective effect of grape wines in nitrosative stress caused by experimental
      diabetes mellitus].
AB  - It was found that under the diabetes-induced oxidative-nitrosative stress, red
      and white wines, which polyphenols are considered to be the main active
      components, decrease the level of nitrotyrosine-modified proteins toward the
      control level in sciatic nerve, dorsal root ganglia and spinal cord of animals
      with diabetes mellitus. A decrease of the activity of poly(ADP-ribose)polymerase
      1 to the control level in the sciatic nerve of diabetic rats with red wine
      consumption was also shown. During the experiment the body weight of the control
      group and diabetic groups of rats with consumption of red wine was significantly
      increased by 52% and 19% accordingly. The present results allow us to assume an
      important role of red wine and possibility of production of its preparations for
      prevention and treatment of diabetic neuropathy.

PMID- 20684236
TI  - [The role of Src-tyrosine kinases in increasing vascular permeability during
      experimental ulcerative colitis].
AB  - We have shown the increase of Src(Tyr416) phosphorylation in rat colonic mucosa
      at early stages of 6% iodoacetamide-induced ulcerative colitis (UC), while the
      level of Src protein expression was not changed. Pretreatment of rats with Src
      inhibitor PP1 (0.2 mg/100 g, subcutaneously) decreased the colonic vascular
      permeability (VP) (P < or = 0.001) and pSrc(Tyr416) level during iodoacetamide
      UC. Iodoacetamide-induced autophosphorylation and upregulation of VEGFR-2 was
      associated with Src activation in colonic mucosa of rats. Sequentially, protein
      protein interaction between beta-arrestine2 and VE-cadherine was enhanced, that
      might be a reason of colonic endothelium barrier disruption. We concluded that
      Src plays a key role in the mechanisms of increasing the colonic VP during
      experimental UC.

PMID- 20684237
TI  - [Thrombin inhibitors which display antibacterial activity].
AB  - The investigation of cytotoxicity and antibacterial activity of the novel
      thrombin inhibitors containing retro-D-sequences -D-Arg-D-Phe--modified by D
      arginine amino group by the residues of lauric acid or chromone-contained
      substituent, in comparison with known cationic preservative Nalpha-lauroyl-L
      arginine ethyl ester (LAE) have been carried out. It has been shown that compound
      Laur-D-Arg-D-Phe-OMe has a similar cytotoxicity with LAE, and Chrom-D-Arg-D-Phe
      OMe has almost twice higher toxicity than it fatty moiety contained analogues.
      Antibacterial activity of Laur-D-Arg-D-Phe-OMe against Staphylococcus aureus and
      Bacillus subtilis is close in action to LAE. It is assumed that ability of
      thrombin inhibitors to suppress the growth of some microorganisms can be
      explained by their ability to suppress activity of trypsin-like serine
      proteinases, which participate in the infection process of Staphylococcus aureus
      and influence on Bacillus subtilis sporulation. These findings open new prospects
      for exploring efficient antimicrobial agents among synthetic low-molecular
      trypsin-like serine proteinase inhibitors.

PMID- 20684238
TI  - [Rashba Olena Iakivna--a gifted scientist and science organizer].
AB  - Professor Olena Yakivna Rashba, doctor of science in biology, was born in Kyiv,
      to the physician's family; graduated from the Medical-Prophylactic Faculty of the
      First Medical Institute (1927-1931). Since 1933 she had been working at the
      Institute of Biochemistry of the Academy of Sciences of Ukr.SSR: first as a
      laborant and then as a junior and as a senior scientific worker. In 1939 O. Ya.
      Rashba defended a thesis for the Candidates degree in biology, and in 1951 the
      thesis for the Doctor's degree. From 1943 to 1945 O. Ya. Rashba was at the front
      as the major of Medical Service. She was awarded the Red Star Order and medals
      For Capture of Berlin and For the Victory over Germany in the Great Patriotic War
      of 1941-1945. Before 1941 Olena Yakivna investigated, under the supervision of
      Acad. O. V. Palladin, biochemical topography of departments of the central and
      peripheral nervous system, as well as variations in content of protein and its
      metabolism products in different departments of brain during embryonal
      development of vertebral animals. In 1945-1951 O. Ya. Rashba began investigating
      peculiarities of carbohydrate metabolism in the brain. The data obtained by the
      scientist evidence that two enzymes (amylase and maltase) function in the brain
      which split glycogen to glucose in hydrolytic way. Interrelation between
      amylolytic and phospholytic enzymatic systems was detected in these experiments.
      Olena Yakivna has also developed the method of obtaining nuclei from the cells of
      nerve tissue and studied their composition. From 1951 to 1973 O. Ya. Rashba
      headed the Department of Microorganisms of the Institute of Microbiology of AS of
      Ukr.SSR and was a co-author of the efficient drug against bacterial cancer of
      tomatos "Arenarin". O. Ya. Rashbe has published about 100 scientific works, 2
      monographs among them; she obtained 2 author's certificates.

PMID- 20684239
TI  - [Oxytocin and its role in the control of intracellular level of calcium ions in
      the myometrium].
AB  - The work deals with the study of molecular and membrane mechanisms of uterotonic
      peptide hormone oxytocin action on Ca ions homeostasis in the uterus myocites and
      activity of passive and active transport systems of this cation, localized in the
      myometrium subcellular structures. Biochemical mechanisms of additional Ca2+
      influx into the myometrium cells from extracellular environment activated by
      oxytocin and thapsigargin were determined. Such Ca2+ influx has got the name of
      capacitative cation entry (CCE), or which is activated by intracellular store
      depletion (store-operated calcium entry). It was shown that cells from the
      nonpregnant human myometrium and PHM1-41 cells (immortalized pregnant human
      myometrial cells) expressed endogenous hTrpC1, 3, 4, 6 and 7 mRNA. The membrane
      permeable derivative of diacylglycerol (OAG) stimulated an increase in
      oscillations of intracellular free Ca2+ concentration in PHM1-41 and myometrium
      cells. OAG-induced Ca2+ -oscillations were not affected by inhibition of PKC. It
      was proved that hTrpC channels take part in the regulation of free Ca ions
      concentration in the myometrium cells. On the basis of results of experiments,
      conducted on myometrium plasma membrane fraction, the conclusion was made that
      oxytocin does not influence the passive Ca2+ efflux. It was shown that peptyde
      hormone partially inhibited Ca2+ accumulation in plasma membrane fraction.
      Oxytocin also partially inhibited endoplasmic reticulum calcium pump activity of
      the myometrium cells. The conceptual pattern of myometrial Ca2+ exchange
      regulation by oxytocin is offered.

PMID- 20684240
TI  - [New non-peptide inhibitors of furin].
AB  - Furin, a human subtilisin-related proprotein convertase, is the most important
      pharmaceutical target because it plays a vital role in development of numerous
      disease processes. To identify a new class of small non-peptide inhibitors of
      furin we performed a study of several flavonoids and some natural products.
      Glycosylated flavonoids: rutin, naringin, baikalin and methylhesperidin were
      shown to inhibit furin at pH 7.2 reversibly and competitively with Ki- 80-200
      microM. The Ki values were derived from Dixon and/or Eadie-Hofstee plots using
      fluorogenic substrate Boc-Arg-Val-Arg-Arg-AMC. Although studied flavonoids
      display only a temperate furin inhibition, they may serve as a great potential
      for the future development of more potent non-peptide inhibitors against furin.

PMID- 20684241
TI  - [Thermoinactivation of potato 5-lipoxygenase and effect of phosphatidic acid on
      activation energy of denaturation].
AB  - The investigation aim was to establish the structural-functional relations of
      individual lipid metabolism components: enzymes--lipoxygenases and membrane
      phospholipids. Influence of phosphatidic acid (PA)--allosteric activator of
      potato tuber 5-lipoxygenase (5-LO)--on thermoinactivation thermodynamic
      parameters of enzyme was studied. It was established that PA changes essentially
      the 5-LO thermostability, namely activation energy Ea of enzyme denaturation
      increases several times in this phospholipid presence. Such changes can evidence
      that PA interaction with 5-LO leads to conformational changes of enzyme probably
      due to hydrophobic interactions. Obtained results give a possibility to interpret
      the action mechanism of PA as 5-LO allosteric activator, which can displace the
      substrate molecules in binding sites and increase the level of formation of
      specific products of linoleic acid oxygenation by 5-LO.

PMID- 20684242
TI  - [Comparative characteristic of lactate dehydrogenase properties from the white
      muscles and liver of goldfish (Carassius auratus L.)].
AB  - Lactate dehydrogenase (LDH) from the liver and white muscles of the gold fish
      Carassius auratus was partially purified by differential precipitation with
      ammonium sulfate. The enzyme from the liver had relatively low Vmax--1.85 +/-
      0.31 U/mg protein, the muscle enzyme--3.74 +/- 0.27 U/mg protein. LDH from the
      liver was less sensitive to substrate inhibition (I50 - 9.92 +/- 1.09 mM)
      compared to white muscles isozyme (I50 - 5.87 +/- 1.39 mM). The studied isozymes
      had pH-dependencies with pH optima at 7.0-8.0 and 7.25-8.75 for LDH from the
      white muscle and liver, respectively. In this work the inactivation of partially
      purified LDH in the system free radicals oxidations Fe2+/H2O2 has been conducted.
      During incubation for 5 min of both isozymes with H2O2 (10-50 mM) and FeSO4 (20
      500 microM), approximately 50% of their initial activities were lost. The level
      of enzyme inactivation increased with the increase of iron ion and hydrogen
      peroxide concentrations. During incubation in the presence of 20 microM FeSO4 and
      10 mM H2O2 for 60 min white muscles isozyme lost 44% while liver isozyme--26%,
      independent of buffer which was used.

PMID- 20684243
TI  - [Contents of monovalent cations and ATP in erythrocytes of marine fishes in
      experimental hypoxia].
AB  - Coupling of membrane and metabolic functions in nuclear erythrocytes was
      investigated under experimental hypoxia conditions in fishes (Liza aurata,
      Scorpaena porcus) with different tolerance to oxygen deficiency. It was shown,
      that resistant to hypoxia Scorpaena porcus keeps in erythrocytes transmembrane
      gradients of K+ and Na+ and cellular concentration ATP under 15% of oxygen
      saturation of sea water. It was connected with the decrease in Na+, K+ -ATPase
      and hexokinase activity. The reaction to oxygen deficiency was opposite in
      sensitive to hypoxia Liza aurata erythrocytes. A decrease in ionic gradients and
      concentration of ATP in red blood cells was observed while the activity of Na+,
      K+ -ATPase and hexokinase was high. The reasons of the differences obtained are
      discussed.

PMID- 20684244
TI  - [Protective effect of N-stearoylethanolamine in acute alcohol intoxication in
      rats].
AB  - The influence of N-stearoylethanolamine on the nitric oxide system, the state of
      lipid peroxidation, antioxidant enzyme activity, content of phospholipids and
      fatty acids were studied under the acute ethanol intoxication (2.5 g/kg) in rats.
      The results of investigations show that acute ethanol intoxication caused
      abnormalities of the oxidative homeostasis accompanied by the accumulation of
      thiobarbituric acid reactive substances (TBARS). High catalase and glutathione
      peroxidase activity was also shown. The altered content of total and individual
      fatty acids of phospholipids in the rat liver tissue was found. The content of
      saturated fatty acids (palmitic, stearic) increased and amount of unsaturated
      (palmitoleic, oleic, linolenic) acids decreased under acute ethanol intoxication.
      The changes of nitric oxide content was found in the brain, plasma and red blood
      cells. N-stearoylethanolamine (NSE) in a dose of 50 mg/kg of body weight shows
      the pronounced antioxidative and hepatoprotective properties under these
      conditions. It was found that the preliminary NSE administration to rats
      inhibited accumulation of TBARS and caused a simultaneous increase of antioxidant
      enzyme activity. The NSE administration modulated also the content of total and
      individual fatty acids of phospholipids and the amount of nitric oxide in
      pathologically altered tissues. These results suggested that NSE protected the
      structural integrity and functional ability of cell membranes under the acute
      ethanol intoxication.

PMID- 20684245
TI  - [B-, H- and L-cathepsin-like activity in blood plasma of patients with diseases
      of the thyroid, parathyroid and adrenal glands].
AB  - B-, H- and L-catepsine-like activity regarding Na-benzoyl-D,L-arginine-4
      nitroanilide, L-leucine-4-nitroanilide and azocasein was studied in the blood
      plasma of patients with different diseases of thyroid, parathyroid and adrenal
      glands. It has been shown that the high H- catepsine-like activity confirming the
      activation of blood catepsin H secretion accompanied by the tissue growth under
      any pathology took place in the blood plasma of patients with all the above
      diseases. High B- catepsine-like activity in the blood plasma of patients with
      thyroid diseases was exceptionally fixed under the nodular forms of thyroid
      pathology, while the character of changes in L catepsine-like activity under
      these diseases was not so natural. In diaseses of the adrenal glands the changes
      in the B- and L-catepsine-like activity were only shown in the blood plasma of
      patients with cerebral layer tumors but not the gland cortex: B-catepsine-like
      activity increased in the blood plasma of patients with benign or malignant
      tumors, and L-catepsine-like activity decreased under benign tumor from
      chromaffin tissue. The established picture of changes in enzymatic activity in
      the blood plasma of patients does not allow to think that the determination of
      blood B- and L- catepsine-like activity can be recommended for obtaining
      additional information at diagnosis thyroid diseases.

PMID- 20684246
TI  - [Effect of thiolactone homocysteine loading on adenosine metabolism in rats:
      relationship with platelet hyper-reactivity, correction of this metabolism
      disorders by vitamin-microelement complex].
AB  - Influence of DL-homocysteine thiolactone loading (100 mg/kg by intragastric
      administration for 28 days) on enzymes activity of adenylic nucleotide and
      adenosine metabolism in the blood serum, platelets and liver of rats was
      investigated. The relation between revealed disturbance and platelet hyper
      reactivity was estimated. It was established, that apyrase and 5'-nucleotidase
      activities decreased and adenosine deaminase activity increased in platelets of
      the rats with hyperhomocysteinemia (HHC). HHC also interrupted adenosine
      production in the blood serum and liver in rats. Under this condition the
      platelet sensitivity to ADP-stimulation was significantly increased. Vitamin
      microelement complex decreased HHC-induced disorder of adenosine metabolism and
      prevented platelet hyper-reactivity formation. In vitro homocysteine inhibited
      platelet hydrolysis of ADP and AMP in a dose-dependent manner and this effect
      reduced in the presence of hydrogen sulfide donor NaHS.

PMID- 20684247
TI  - [Features of cholecalciferol hydroxylation in the liver of rats in conditions of
      D-hypervitaminosis and activity of alpha-tocopherol].
AB  - It is shown, that hepatocytes contain two (microsomal and mitochondrial) vitamin
      D3 25-hydroxylase enzymes, which differ as to their activity and function with
      maximal activity at different concentrations to substrate, namely at 15 microM
      and 100 microM of vitamin D3, accordingly. Activity of vitamin D3 25-hydroxylase
      enzymes of hepatocytes is regulated by cholecalciferol and alpha-tocopherol. The
      general and microsomal vitamin D3 25-hydroxylase enzymes activity of hepatocytes
      is lowered, but mitochondrial isoform is increased under D-hypervitaminosis
      conditions. Vitamin E increases microsomal vitamin D3 25-hydroxylase activity and
      decreases mitochondrial isoform activity of rats hepatocytes under D
      hypervitaminosis conditions. It is established that D-hypervitaminosis is
      accompanied by expressed hypercalcemia and hyperphosphatemia, by decreased
      contents of mineral components in the bone tissue and high activity of alkaline
      phosphatase in the blood serum. The physiological doses of vitamin E under these
      conditions normalized the mineral metabolism, contents of calcium, phosphates and
      activity of alkaline phosphatase isoform in the blood serum.

PMID- 20684248
TI  - [Adaptation of antioxidative system in rat kidneys under varying light conditions
      during tetrachloromethane intoxication and effect of melatonin].
AB  - The influence of varying light conditions of the state of pro- and antioxidative
      systems in rat kidneys has been studied. The lowest level of free radical
      oxidation of lipids and proteins and the highest activity of catalase and
      glutathione peroxidase in the rat kidneys was established in case of maximal
      duration of the light day. Under different light conditions the increase of
      malonic aldehyde and oxidatively modified proteins in the rat kidneys in case of
      tetrachloromethane intoxication was shown as compared with the control. It was
      established, that melatonin introduction during 5 days in a doze of 3.0 mg/kg of
      body weight reduces the content of products of free radical oxidation of lipids
      and proteins and shows the normalizing effect on the indices of antioxidative
      system in rat kidneys.

PMID- 20684249
TI  - [Computer modeling of interaction of calix[4]arene C-99 with subfragment-1 of
      myometrium myosin].
AB  - In this work the computer design of interaction of calix[4]aren C-99 with a
      substrate-binding center of a functionally active area of a subfragment-1 myosin
      of the myometrium is carried out. It is shown when using methodology of molecular
      docking the receipt of ligand-receptor complexes which have geometry concerted
      with experimental data is possible. The cross-coupling of ATP and calix[4]aren C
      99 on their orientation in ligand-binding center of subfragment-1 myosin of
      myometrium has been studied.

PMID- 20684250
TI  - [Computer modeling of the human cytochrome P-450 2E1 complex formation].
AB  - A comparison has been made between spatial structures of human CYP2E1 obtained
      experimentally and those calculated using the computer methods. The structures
      were characterized by such parameters as total energy, protein pocket volume and
      total volume of molecules as well as the analysis of spatial geometry. The
      obtained results have proved that the model calculated and optimized by us can be
      used for studing the mechanisms of interaction of the active center of the enzyme
      with substrates and inhibitors. An assumption was made in the course of the
      research that one of the possible mechanisms of inactivation of the enzyme is the
      reduction of protein pocket volume, which prevents substrate access to the active
      center.

PMID- 20684251
TI  - Apoptosis and content of mobile lipid domains in human leukemia K-562 cells
      induced to differentiate by quercetin or dimethyl sulfoxide.
AB  - The apoptotic index, cell cycle progression and caspase-3 activation in K-562
      cells induced to differentiate by DMSO or quercetin have been studied. Quercetin
      treatment of K-562 cells was accompanied by cell cycle arrest in G2/M and
      apoptosis with caspase-3 activation. In contrast, DMSO-induced differentiation
      was accompanied by the complete cell cycle arrest in G1/G0 with negligible
      caspase-3 activation. In spite of the appearance of benzidine-positive cells and
      the decreased CD71 level in K-562 cells after exposure to quercetin, the analysis
      of 1H NMR spectra revealed the overall balance in favor of apoptosis, namely the
      increase in the content of NMR-visible mobile lipid domains and the decreased
      intensity of choline-containing metabolites.

PMID- 20684252
TI  - [Avidity of IgG antibodies and its theoretical evaluation].
AB  - A new method, which allows evaluation of the avidity of bivalent antibodies when
      they react with bivalent antigen, is suggested. The theory is based on the idea
      that was proposed by us earlier. That theory considered the relation between
      affinity constants for bi-molecular and mono-molecular reactions of the reagents,
      which either are connected or not connected by a flexible linker. Using the
      suggested theory it makes possible to calculate antibody avidity if the affinity
      and molecular structure of the antibody are known. The obtained by us theoretical
      results completely coincide with the experimental values of antibody avidity that
      are known from literature.

PMID- 20684253
TI  - Public health and MSD: a necessary union.

PMID- 20684254
TI  - Together we can do so much.

PMID- 20684255
TI  - State of Delaware response to novel H1N1 influenza: Division of Public Health's
      perspective.
AB  - The novel H1N1 influenza in 2009 and 2010 demonstrated the important relationship
      between medicine and public health. Delaware physicians may benefit from knowing
      how the state Division of Public Health (DPH) responded. One way to describe that
      response is to compare H1N1 influenza activities to the Ten Essential Public
      Health Services, adopted as standard practice by most public health agencies.

PMID- 20684256
TI  - You just left your wallet on the table.

PMID- 20684257
TI  - Forty-six years and counting.

PMID- 20684258
TI  - [P38 MAPK antisense oligodeoxynucleotide inhibited the brain ischemic tolerance
      induced by limb ischemic preconditioning].
AB  - OBJECTIVE: To better assess the role of p38 MAPK, this project was designed to
      investigate whether intraventricular injection of antisense oligodeoxynucleotide
      (As-ODN) directed against the p38 MAPK of pyramidal neurons in hippocampus could
      affect the brain ischemic tolerance induced by limb ischemic preconditioning
      (LIP). METHODS: The rat 4-vessel occlusion global cerebral ischemic model was
      used. Forty-eight male Wistar rats with permanently occlusion of the bilateral
      vertebral arteries were divided into 8 groups (n=6): sham, LIP, brain ischemic
      insult, LIP + brain ischemic insult, distilled water + LIP + brain ischemic
      insult, p38 MAPK As-ODN and p38 MAPK As-ODN + LIP + brain ischemic insult (two
      doses of 5 nmol/5 microl and 10 nmol/5 microl were used) groups. Thionin staining
      was used for observing histological changes of the hippocampus. RESULTS: No
      significant delayed neuronal death (DND) was detected in the CA1 hippocampus of
      the rats that underwent sham and LIP operation. Brain ischemic insult for 8 min
      induced obvious DND as represented with the increase in histological grade (HG)
      and decrease in neuronal density (ND) significantly compared with sham and LIP
      groups. LIP protected the CA1 hippocampal pyramidal neurons against DND induced
      by global brain ischemic insult, suggesting the occurrence of brain ischemic
      tolerance. However, pretreatment with p38 MAPK As-ODN effectively blocked the
      ischemic tolerance induced by LIP in a dose dependent manner. CONCLUSION: It
      could be concluded that p38 MAPK plays an important role in the brain ischemic
      tolerance induced by LIP.

PMID- 20684259
TI  - [Hypoxia enhances the proliferation of skeletal myoblasts and possible
      mechanism].
AB  - OBJECTIVE: To explore the role of hypoxia in skeletal myoblasts proliferation and
      related mechanism. METHODS: The numbers and proliferous indexes of skeletal
      myoblasts were detected by flow cytometer under 20%, 3%, and 10% oxygen
      concentration. Hypoxia inducing factor 1alpha (HIF-1alpha) mRNA expression was
      determined by reverse transcriptase-polymerase chain reaction (RT-PCR). HIF
      1alpha proteinum in endochylema and intranucelus were respectively detected by
      Western blot. RESULTS: The numbers and proliferous indexes were higher (P < 0.05)
      in hypoxia group than those of control group. The expression HIF-1alpha mRNA had
      no difference in hypoxia and in normal groups. The level of HIF-1alpha proteinum
      in endochylema under normoxia was more than that in intranucelus and it was
      opposite under hypoxia. CONCLUSION: Hypoxia can promote the proliferation of
      skeletal myoblasts. The possible mechanism of hypoxia promoting the proliferation
      of skeletal myoblasts might be that low oxygen concentration regulates HIF-la
      nuclear translocation.

PMID- 20684260
TI  - [Suitable oxygen concentration for rat model's hypoxic preconditioning].
AB  - OBJECTIVE: To study the suitable oxygen concentration in hypoxic preconditioning.
      METHODS: Short-term and long-term intermittent hypoxia modes were designed and
      the effects of various oxygen concentrations on body weight, blood oxygen
      saturation, swimming capability were analyzed. RESULTS: The rate of body weight
      gain in rat model decreased gradually when exposed to hypoxia environment for
      long time. When the concentration of oxygen changed from 15% to 8%, accompanied
      with the decreasing of oxygen concentration, a platform was observed in blood
      oxygen saturation of rat model after hypoxic preconditioning training. Rat
      swimming capability improved significantly. After trained in 10% hypoxia
      environment, the swimming capability of kunming mice improved obviously.
      CONCLUSION: Proper level of hypoxic preconditioning training could improve
      hypoxia tolerance and enhance the rat sport capability significantly. 15%-10%
      oxygen concentration range could be regarded as a helpful effective area for
      hypoxic preconditioning, 10% oxygen concentration might be the eligible
      concentration for hypoxic preconditioning training.

PMID- 20684261
TI  - [Effects of pravastatin on the expression of transforming growth factor-beta 1 in
      cardiac fibroblasts].

PMID- 20684262
TI  - [The subgroup change of nitric oxide synthase in earlier period with cerebral
      ischemia/reperfusion in rats].
AB  - OBJECTIVE: To observe the expression of endothelial nitric oxide synthase
      (eNOS)and nervous nitric oxide synthase (nNOS) in rats during cerebral
      ischemia/reperfusion (CI/R) and study if change will be happen in subgroup
      between eNOS and nNOS during earlier period of CI/R. METHODS: A total of 60
      Wistar rats weighting 200-280 g, supplied by Animal Center of China Medical
      University, were divided into 6 groups (n=10) (sham operation group; ischemia 1
      h, 2 h group; reperfusion 0.5 h, 1 h, 2 h group). Female and male was half-and
      half. Cerebral ischemia/reperfusion injury was induced by a 2-hour suture
      occlusion of the unilateral middle cerebral artery, immediately after suture
      withdrawal to allow reperfusion, eNOS and nNOS expressions were examined by the
      method of immunohistochemistry. RESULTS: eNOS expressions increased in 1-hour
      during ischemia, keeping up with decreasing until reperfusion 2-hour. While nNOS
      expressions increased in 2-hour between ischemia and reperfusion. CONCLUSION:
      Changes of expression between eNOS and nNOS in rats during cerebral
      ischemia/reperfusion are different. This may be related with ischemia and
      reperfusion injury.

PMID- 20684263
TI  - [Effect of chronic hypoxia on the plasma corticosterone and testosterone levels
      of male rats].

PMID- 20684265
TI  - [Effects of erythropoietin on neural cells in rats after ischemia/reperfusion
      injury].

PMID- 20684264
TI  - [Protective effects of new compound codonopsis tablets against acute mountain
      sickness].
AB  - OBJECTIVE: To study on the protective effects of new compound codonopsis tablets
      against acute mountain sickness (AMS). METHODS: Forty-five male plain resident
      soldiers stayed at 1400 m altitude for 3 months were randomly divided into two
      groups, control (15 men) and treatment group (30 men). Single blind trial was
      used in this study. The subjects in the two groups took placebo and new compound
      codonopsis tablets respectively for 5 days before climbing to high mountain, and
      continued to take for another 10 days until the 3rd day after arriving at 5200 m
      altitude. On the 1st , 3rd, and 5th day after they arrived at 5200 m altitude,
      the score and the degree of AMS symptoms of soldiers were followed up and
      recorded according to State Military Standard GJB1098-91--"Principles of
      diagnosis and treatment of benign form of acute mountain sickness", heart rate
      (beats/min) and arterial oxygen saturation (%) were detenrmined. On the 6th day
      after they arrived at high altitude, forced vital capacity(FVC), forced expired
      volume in one second(FEV1.0), FEV1% (FEV1.0/FVC), FEF25%-75%, peak expiratory
      flow (PEF) and maximal voluntary ventilation (MVV) were detected, total frequency
      of hands cross movement and memory of order numbers test were measured. RESULTS:
      Comparison with control, AMS symptoms of treatment group reduced on the 1st, 3rd,
      and 5th day after arriving at 5200 m high altitude (P < 0.01). The degree of AMS
      symptoms of treatment group was significantly different from that of control. The
      proportion of slight symptoms in treatment group was high, and that of relative
      serious symptoms in control was high. Compared with control, FVC, FEV1.0, FEF25%
      75%, PEF and MVV of treatment group increased (P < 0.05, P < 0.01), and Ttis,
      Ctis of treatment group increased (P < 0.05, P < 0.01), Atime decreased markedly
      (P < 0.05), there was no statistically significant difference in Etis and Sum
      between the two groups. CONCLUSION: New compound codonopsis tablets could
      decrease the incidence of AMS, mitigate the symptoms of AMS, and improve
      breathing function and fingers movement function. New compound codonopsis tablets
      have an obvious effect on prevention and treatment of acute mountain sickness.

PMID- 20684266
TI  - [Auricularia auricular polysaccharide protects myocardium against
      ischemia/reperfusion injury].
AB  - OBJECTIVE: To determine whether auricularia auricular polysaccharide (AAP)
      protects heart against ischemia/reperfusion (1/ R) injury and its underlying
      mechanisms. METHODS: Male Sprague-Dawley rats, pretreated with AAP (50, 100, 200
      mg/(kg x d), gastric perfusion) for 4 weeks, were used for Langendorff isolated
      heart perfusion. The hearts were subjected to global ischemia for 30 min followed
      by 120 min of reperfusion and the left ventricular hemodynamic parameters were
      measured. Formazan, a product of 2, 3, 5-triphenyl-tetrazolium chloride (TTC),
      which is proportional to myocardial viability, was measured at 490 nm, and the
      level of lactate dehydrogenase (LDH) in the coronary effluent was measured to
      evaluate the cardiac injury. The cardiac malondialdehyde (MDA), a product of
      lipid peroxidation, and superoxide dismutase (SOD) activity were determined after
      myocardial I/R. RESULTS: The pretreatment with AAP at 50, 100, 200/(kg d) for 4
      weeks before I/R increased myocardial formazan content, reduced LDH release,
      improved the recovery of the left ventficular developed pressure, maximal rise
      rate of left ventricular pressure, and rate pressure product (left ventricular
      developed pressure multiplied by heart rate) attenuated the decrease of coronary
      flow during reperfusion. The cardiac protective effect of high dose AAP was more
      potent than that of compound radix salviae miltiorrhizae (CRSM, 4 ml/(kg x d),
      gastric perfusion for 4 weeks). Pretreatment with AAP (100 mg/(kg x d)) markedly
      inhibited the increase of MDA level and the decrease of SOD activity induced by
      I/R in myocardium. CONCLUSION: The findings indicate that in the isolated rat
      heart, AAP protects myocardium against ischemia/reperfusion injury via enhancing
      the activity of SOD and reducing lipid peroxidation in heart.

PMID- 20684267
TI  - [The effect of vitamin E on renal ischemia/reperfusion injury in young and aged
      rats].
AB  - OBJECTIVE: To investigate the effect of vitamin E on renal ischemia/reperfusion
      injury (RI/RI) in young and aged rats. METHODS: The model of (RI/RI) was induced
      by bilateral clamping the renal artery and vein for 45 min followed by
      reperfusion. The contents of BUN, Scr, MDA, SOD, NO and iNOS were measured.
      Proteins of HSP70 were observed by immunohistochemistry. Flow cytometer was used
      to estimate the apoptosis rate of renal cortex cells. RESULTS: After
      ischemia/reperfusion injury, the contents of BUN, Scr and iNOS were increased.
      Compared with young ischemia/reperfusion group, the contents of MDA were higher
      and the contents of SOD were lower in aged ischemia/reperfusion group. The
      expression of HSP70, the contents of NO and the apoptosis rate of renal cortex
      cells were higher in aged ischemia/reperfusion group than that in control group.
      Vitamin E significantly decreased the contents of BUN, Scr, MDA and iNOS, and
      increased the contents of NO and SOD after RI/RI. The expression of HSP70 was
      increased in both VE groups than that in both I/R groups. The apoptosis rate of
      renal cortex cells was less in both VE groups than that in both I/R groups.
      CONCLUSION: Vitamins E may up-regulate the expression of HSP70, increase the
      contents of SOD and NO, and enhance an ability of clear free radicals, which may
      contributes to decreasing renal ischemia/reperfusion injury in young and aged
      rats.

PMID- 20684268
TI  - [Role of HO-1 in the myocardial cell delayed preconditioning].

PMID- 20684269
TI  - [Roles of proto-oncogene c-erbB2 during the initiation growth of rat primordial
      follicles].
AB  - OBJECTIVE: To study the expression and possible roles of proto-oncogene c-erbB2
      during the initiation growth of primordial follicles. METHODS: Ovaries were
      collected from 2-day-old SD rats and cultured in the Waymouth culture system. In
      situ hybridization, RT-PCR and immunohistochemistry were performed to assess the
      expressions of c-erbB2 mRNA and protein during the initiation growth of
      primordial follicles and after the effect of EGF. Western blot was used to
      observe the PCNA, p-ERK1/2 contents and correlation analysis was used to study
      the correlation relationship between contents of p-ERK1/2 and expressions of c
      erbB2 mRNA at the same time of the primordial follicles growth. RESULTS: PCNA
      protein levels appeared to be more intense during the initiation growth of
      primordial follicles, EGF could promote the proliferation and differentiation of
      the primordial follicles. c-erbB2 mRNA existed in the oocytes endochylema and
      ErbB2 existed in the oocytes membrane, the expressions of c-erbB2 mRNA and ErbB2
      appeared to be more intense when primordial follicles were cultured for 8 d than
      cultured for 0 d in the Waymouth culture system and were further increased with
      50 ng/ml EGF for 4 d and 8 d. The same results were observed by RT-PCR, too. p
      ERK1/2 protein levels were consistent with the changes of c-erbB2 mRNA and
      protein. Furthermore, Spearman rank correlation analysis showed there was a
      significant positive correlation relationship between the changes of p-ERK1/2 and
      the changes of c-erbB2 mRNA during the primordial follicles growth and after the
      effect of EGF (rs = 0.900, P < 0.05). CONCLUSION: It was suggested that proto
      oncogene c-erbB2 may be play an important role during the initiation growth of
      primordial follicles with EGF, and it is indirectly suggested that c-erbB2
      promotes the development of the primordial follicles via ERK-MAPK signal
      transduction.

PMID- 20684270
TI  - [Study about power spectral entropy and its application in EEG in epileptic
      rats].

PMID- 20684271
TI  - [Expression and clinical significance of VEGF and apoptosis in frozen-thawed
      mouse ovaries after transplantation].
AB  - OBJECTIVE: To investigate expression and clinical significance of VEGF and
      apoptosis in frozen-thawed mouse ovaries after transplantation. METHODS: Ovaries
      from B6C2F1 (C57BL/6j x BALB/c) 4 week old mice were cryopreservation and the
      thawed ovaries were xenografted into kidney capsules of 8-12 week old adult male
      mice. The grafted were recovered 1 d, 2 d and 7 d after transplantation
      respectively, the grafts and frozen-thawed were removed for follicle counting and
      immunohistochemically, ultrastructure, and detection of the mRNA expression of
      vascular endothelial growth factor(VEGF). RESULTS: The follicle numbers were
      decreased gradually after transplantation,the cell apoptosis increased especially
      in 48 h after transplantation. Transmission electron microscopy (TEM) showed the
      tissue damaged was severest 48 h after transplantation; the expression of VEGF
      increased after transplantation, peaked on day 7, the mRNA expression of VEGF120
      and VEGF188 was more on 48 h after transplantation, decreased on day 7 (P <
      0.05). CONCLUSION: The number of follicles was decreased after transplantation,
      the apoptosis index was increased especially in 48 h after transplantation; the
      expression of VEGF increased after transplantation, an increase in the VEGF188
      and VEGF164 isoform might suggest the positive effect in the early stages of
      angiogenesis.

PMID- 20684272
TI  - [Effects of yikunning on the expressions of bcl-2 and bax in rat ovaries during
      perimenopausal period].
AB  - OBJECTIVE: To investigate the effects of Yikunning (YKN, Chinese Traditional
      Medicine) on the expressions of bcl-2 and bax in rat ovaries during
      perimenopausal period. METHODS: Thirty female Wistar rats during perimenopausal
      period were selected by unforced aging. Then the rats were divided into 3 groups
      randomly: YKN group, Livial control group and Aged control group. Ten young
      female Wistar rats were selected as young control group. Intragastric
      administrations were conducted for 4 weeks once daily continuously. The
      expressions of Bcl-2 Bax mRNAs and proteins in rat ovaries were detected by RT
      PCR and Western blot. RESULTS: The levels of Bcl-2, Bax mRNAs and proteins in rat
      ovaries in YKN group were higher than those in Aged control group, which showed
      differences among them (P < 0.01). The Bcl-2/Bax mRNA rate and protein rate in
      rat ovaries in YKN group were higher than those in Aged control group, which
      showed differences among them (P < 0.05 or P < 0.01). CONCLUSION: YKN could
      increase the expressions of Bcl-2, Bax mRNAs and proteins and up-regulate the Bcl
      2/Bax mRNA rate, protein rate in rat ovaries during perimenopausal period, which
      might be one of the molecular mechanisms of YKN postponed the ovarian failure and
      cured perimenopausal syndrome.

PMID- 20684273
TI  - [Determination of oxidative damage on DNA in brain and kidney of mice induced by
      anti-tumor agent of cisplatin].

PMID- 20684274
TI  - [The effects of hypoxia during pregnancy on sexual behavior of male offspring].
AB  - OBJECTIVE: To investigate the effects of hypoxia during the prenatal period and
      its later repercussions on sexual behavior and the sex hormone secretion of male
      rats. METHODS: Experimental animals were divided into three groups randomly:
      control group, which was kept at normal atmospheric pressure, and two stress
      groups exposed to a simulated altitude equivalent to 3000 m and 5000 m,
      respectively. Stress groups were exposed to hypoxic circumstance at their final
      week of gestation in animal decompression chamber. RESULTS: Adulthood, males
      exposed to hypoxic stress during the prenatal period were able to mate with
      normal females, but these treated males exhibited decreased male sexual behavior.
      Decreased anogenital distances were observed in male offspring, and presented
      reductions of plasma testosterone levels, increase of plasma corticosterone
      levels, but no notable alteration in the organ index. CONCLUSION: These results
      indicate that exposure to hypoxia in the later stages of pregnancy may have a
      long-term effect on the fertility and sexual behavior of male offspring.

PMID- 20684275
TI  - [Abeta(25-35) and ginsenoside Rb1 influence on the expression of GSK-3beta, CDK-5
      and PP2A in differentiated neural stem cells of rats].
AB  - OBJECTIVE: To explore the expression of GSK-3beta, CDK-5 and PP2A and the
      regulation of them by Abeta(25-35) and ginsenoside Rb1 after neural stem cells
      (NSCs) are transformed into neurons. METHODS: To culture NSCs from the dentate
      gyrus of newborn rats(24 h) hippocampus in vitro. NSCs of the third passage were
      induced towards neurons; the expressions of GSK-3beta(pTyr279,216), PP2A and the
      regulation of them by Abeta(25-35) and ginsenoside Rb1 were tested by the
      immunofluorescence cytochemical staining after NSCs had been induced for one
      week; The expressions of GSK-3beta, CDK-5, PP2A and the regulation of them by
      Abeta(25-35) and ginsenoside Rb1 were detected with RT-PCR. RESULTS:
      Immunofluorescence cytochemisty showed that neural cells from NSCs which had been
      differentiated after one week could express GSK-3j (pTyr279,216)and PP2A.
      Abeta(25-35) could enhance the expression of GSK-3beta(pTyr279,216), meanwhile it
      also restrained the expression of PP2A. Moreover ginsenoside Rb1 could reverse
      the affect of Abeta(25-35). RT-PCR found that neural stem cells which had been
      differentiated after one week could express GSK-3beta, CDK-5, PP2A . The
      expression of GSK-3beta and CDK-5 rose up and the expression of PP2A weakened
      when they were treated by Abeta(25-35). However, the effect of Abeta(25-35) was
      restrained when they were pretreated by ginsenoside Rb1. CONCLUSION: These
      observations indicated that NSCs which were cultured and induced in vitro can
      express GSK-3beta, CDK-5 and PP2A; moreover Abeta(25-35) and ginsenoside Rb1 can
      regulate the expressions of GSK-3beta, CDK-5 and PP2A. It hints that cells which
      differentiated from neural stem cells in vitro have protein phosphorylation
      regulation system of normal cells.

PMID- 20684276
TI  - [The effect of AGS3 on the I(A) of newborn rat prefrontal cortical neurons
      pretreated by chronic morphine].
AB  - OBJECTIVE: The effect of chronic morphine treatment on the I(A) (transient
      outward K+ current) of prefrontal cortical neurons of newborn rat. On this basis,
      we use AGS3 antibody to inhibit the function of AGS3, for observing the impact of
      AGS3 on the I(A), thus further explore the mechanism of AGS3 protein in morphine
      addiction. METHODS: By using whole-cell patch-clamp technique, I(A) was recorded.
      In the whole-cell configuration, observed the impact of morphine on the current
      density-voltage curve (I-V) of I(A) and the effect of AGS3 antibody with three
      different concentrations on the I(A) of morphine treated rat prefrontal cortical
      neurons. RESULTS: Morphine increased the I(A). When the test potential was + 55
      mV, different concentrations of AGS3, 10(-3) microg/L, 10(-2) micdrog/L and 10(
      1) microg/L acted on morphine treated rat prefrontal cortical neurons, the
      enhanced IA by morphine was inhibited. CONCLUSION: Morphine increases the I(A),
      AGS3 protein may participate in signal transduction pathway involved with I(A).

PMID- 20684277
TI  - [Establishing the model of kappaB-decoy inhibiting the activity of NF-kappaB in
      PC12 cells].
AB  - OBJECTIVE: Observing the time course and establishing the model of kappaB-decoy
      oligodeoxynucleotides (rcB-decoy) inhibiting the activity of NF-kappaB in the
      PC12 cells. METHODS: PC12 cells cultivating in the 6 wells plate were divided
      into 3 groups, experimental group: adding kappaB-decoy complex (6 microg
      DNA/well), the control group: adding scrambled-decoy complex, the normal group:
      adding lipid-Lipofectamine 2000, transfer and cultivate 48 h, then
      lipopolysaccharide (LPS, 200 ng/ml) was added in the cells for 0.5-4 h. The
      immunocytochemistry and Western blot were used to measure the expression or the
      activity of NF-kappaB in PC12 cells. RESULTS: In PC12 cells, compared with normal
      group, the expression of NF-kappaB enhanced obviously with the time of the
      stimulation of LPS in scrambled-decoy treated control group (P < 0.01), in 2-4 h
      the level reached the peak; the expression of NF-kappaB showed the stable level
      with the time of the stimulation of LPS in kappaB-decoy treated experimental
      group, compared with the control group, the expression levels were obviously
      lower than the respective time point of control groups (P < 0.01). CONCLUSION:
      kappaB-decoy could reduce the expression of NF-kappaB in the normal PC12 cells
      and inhibit the activity of NF-cB in the pathologic PC12 cells.

PMID- 20684278
TI  - [Interleukin-18-induced transdifferentiation in renal proximal tubular cells is
      mediated by activation of p38MAPK pathway].
AB  - OBJECTIVE: To explore the effect of p38MAPK signaling pathway in interleukin-18
      induced transdifferentiation in renal proximal tubular cells. METHODS: Human
      proximal tubular epithelial cell line (HK-2 cells) was cultured in vitro. After
      preincubated with SB203580 (0, 5, 10, 20 micromol/L) for 30 minutes, cells were
      exposed to IL-18 (100 ng/ml) for 24, 48 and 72 hours respectively. The
      expressions of a-smooth actin (alpha-SMA) in cultured HK-2 cells were assessed by
      RT-PCR and ELISA. RESULTS: IL-18-induced expressions of a-SMA mRNA and protein
      were inhibited obviously by a dose-dependent manner when HK-2 cells were
      incubated with SB203580 (0, 5, 10, 20 micromol/L) and IL-18 (100 ng/ml) for
      different time (P < 0.05). CONCLUSION: IL-18-induced transdifferentiation of
      renal tubular epithelial cells (RTECs) is suppressed obviously by blocking
      p38MAPK signaling pathways. IL-18-induced transdifferentiation of RTECs is
      probably mediated, at least in part, through the activation of p38MAPK signaling
      pathways.

PMID- 20684279
TI  - [Protective effects of IGF-1 on cell injuries and tau hyperphosphorylation
      induced by okadaic acid].
AB  - OBJECTIVE: To investigate the effects of insulin-like growth factor-1 (IGF-1) on
      cell injuries and tau hyperphosphorylation induced by okadaic acid (OA). METHODS:
      The experimental groups were designed as follows: (1) SH-SY5Y culture (control
      group); (2) SH-SY5Y exposed to 40 nmol/L OA for 24 hours (OA group); (3) SH-SY5Y
      exposed to OA for 24 hours in the presence of 2 hour pretreatment with 100, 200
      and 400 ng/ml IGF-1 (IGF-1 pretreatment groups). The changes of cell morphology
      were observed by inverted microscope. The viability of cells was detected by MTT.
      The injuries of cells were examined by Hoechst 33258 staining and the activity of
      caspase-3. Western-blot was applied to determine the expression of
      phosphorylation of tau protein. RESULTS: In IGF-1 pretreatment group, the cell
      morphology was improved, the viability of cells was increased, and caspase-3
      activation and hyperphosphorylation of tau (Ser396) were reduced. CONCLUSION: IGF
      1 can protect the SH-SY5Y cells from cell injuries induced by OA by inhibiting
      tau hyperphosphorylation.

PMID- 20684280
TI  - [Effect of Panax japonicus on anti-oxidation of myocardial mitochondria of rats
      with high-intensity and endurance training].

PMID- 20684281
TI  - [Lymphocyte GRK2 expression of the very elderly with chronic heart failure].
AB  - OBJECTIVE: To explore the correlation of lymphocyte G protein-coupled receptor
      kinases 2 (GRK2) expression of the very elderly with chronic heart failure (HF)
      and heart ejection fraction (EF). METHODS: 16 elderly patients with chronic heart
      failure were divided into 2 groups as following: EF < 45% (n=7), EF > or = 45%
      (n=9); and health elderly as control (n=8). Lymphocytes were obtained from blood,
      reverse transcription polymerase chain reaction were used to measure GRK2 mRNA
      levels. RESULTS: Lymphocyte GRK2 mRNA levels of EF < 45% group were higher than
      that of EF > 45% group, which were greater than that of control. CONCLUSION:
      Elevation of lymphocyte GRK2 levels in HF is associated with heart EF,
      lymphocytes may provide a surrogate for monitoring cardiac GRK2 in human HF.

PMID- 20684282
TI  - [Effects of extremely low frequency sinusoid magnetic field on pain threshold and
      amine acid neurotransmitter of rats].

PMID- 20684283
TI  - [Effects of rosiglitazone on the expression of connective tissue growth factor in
      the pulmonary arteries of rats suffering from fibrosis in lung].
AB  - OBJECTIVE: To explore the effects of rosiglitazone (RSG), an agonist of
      peroxisome proliferators-activated receptor-gamma (PPAR-gamma), on the up
      regulation of connective tissue growth factor (CTGF) and the deposition of type I
      and type III collagens in the pulmonary arteries of rats suffering from fibrosis
      in lung. METHODS: Forty-eight male Sprague-Dawley rats were randomly divided into
      4 groups: bleomycin (BLM) plus normal saline (NS) group (n=21), BLM plus RSG
      group (n=9), NS plus NS group (n=9), and NS plus RSG group (n=9). The rats were
      received single intratracheal instillation of BLM (5 mg/kg bw) or equal volume of
      NS as control, and received intra-gastric adminnistration of RSG (3 mg/(kg x
      day), 14 day) or the same volume of NS as vehicle. In vio, the observation was
      conducted on day 14 after intratracheal instillation. In vitro, the pulmonary
      arteries of rats on day 14 after BLM were isolated and incubated with DMEM alone
      or with RSG (37 degrees C, 5% CO2, for 24 h. RESULTS: In vivo, the expression and
      the content of CTGF, the contents of type I and type III collagens, and the ratio
      of type I collagen and type III collagen were increased in the pulmonary arteries
      of BLM-instilled rats, compared with those of NS-instilled rats (All P < 0.05).
      The above abnormal changes were ameliorated by RSG (All P < 0.05). In vitro, RSG
      blocked the up-regulation of CTGF (P < 0.05), but not the deposition of type I
      collagen and type III collagen in the pulmonary arteries isolated from the BLM
      instilled rats (P > 0.05). CONCLUSION: The results suggest that RSG directly
      blocks the up-regulation of CTGF in pulmonary arteries of rats suffering from
      fibrosis in lung, and this might be one of the mechanisms underling the
      ameliorated pulmonary arterial remodeling by RSG.

PMID- 20684284
TI  - [Changes of body weight, blood glucose in chronic intermittent hypoxic rats and
      protection of iptakalim].

PMID- 20684285
TI  - [The effect of chimonin on collagen metabolism of pulmonary arterioles in chronic
      hypoxic rats].
AB  - OBJECTIVE: To study the effect and mechanism of chimonin on pulmonary arterioles
      I and III type collagen metabolism in pulmonary hypertension rats induced by
      chronic hypoxic hypercapnia. METHODS: Thirty-six Sprague-Dawley rats were
      randomly divided into three groups: normal control group(A), hypoxic hypercapnic
      group(B), hypoxic hypercapnia + chimonin group(C). Collagen I, III and their
      mRNA, Blood CO concentration (COHb%), activity of HO-1 in blood serum and lung
      homogenate, content of hydroxyproline in lung homogenate, pulmonary arteriole
      micromorphometric index were observed. RESULTS: Hypoxic hypercapnic rats's mPAP,
      Hyr of lung homogenate, content of I type collagen and I type collagen mRNA in
      pulmonary arterioles, were significantly higher than those in control group,
      pulmonary vessel remodeling of hypoxic hypercapnic rats was significant, those
      changes in hypercapnia + chimonin group were significantly lower than those in
      hypoxic hypercapnic group. Blood CO concentration, activity of HO-1 in blood
      serum and lung homogenate in rats of hypoxic hypercapnic rats were significantly
      higher than those of control group, and those of hypercapnia + chimonin group
      were even higher than hypoxic hypercapnic group (P < 0.01). There was no
      significant difference in mCAP, content of III type collagen and their mRNA in
      three groups (P > 0.05). CONCLUSION: Chimonin can reduce pulmonary hypertension
      and pulmonary vessel remodeling induced by hypoxic hypercapnia through inhibiting
      proliferation of collagen I, the mechanism maybe is up regulating endogenous
      carbon monoxide system.

PMID- 20684286
TI  - [The interventional effect of anti-basic fibroblast growth factor on the model of
      bleomycin-induced pulmonary fibrosis in rats].
AB  - OBJECTIVE: To study the effect of anti-basic jibroblast grouth factor (bFGF) on
      bleomycin-induced pulmonary fibrosis in rats and its possible mechanism. METHODS:
      Pulmonary fibrosis was induced in Wistar rats by intratracheal instillation of
      bleomycin (model group, group M). Then the rats received anti-bFGF on 1, 2, 3, 8,
      12, 19, 25 days intracavitary injection (group K), normal saline(group C) orally.
      Normal controls received normal saline both intratracheally and orally. Five rats
      in each group were sacrificed on 1.4 week after intratracheal instillation.
      Histological changes of the lungs were evaluated by HE stain and Massons
      trichrome stain. Lung expression of bFGF proteins was assessed by
      immunohistochemistry and the level of bFGF protein in serum and BALF was further
      measured by ELISA. RESULTS: Pulmonary fibrosis of group M was higher than that of
      group C. bFGF in group M was higher than that in group C in lung, serum and BALF
      on 1.4 week. Pulmonary fibrosis of group K was lower than that of group M. bFGF
      in group K was lower than that in group M in lung, serum and BALF on 1.4 week.
      CONCLUSION: Anti-bFGF alleviates bleomycin-induced pulmonary fibrosis in rats.
      Inhibiting the expressions of bFGF in lung tissues may be one of the mechanisms.

PMID- 20684287
TI  - [The regulation of Nrf2/Bachl on gamma-glutamylcysteine synthetase in
      inflammatory cells from bronchial asthmic patient sputum].

PMID- 20684288
TI  - [Effect of vagal nerve stimulation on heart rate and heart rate variability in
      the toads].
AB  - OBJECTIVE: To observe the effect of vagal stimulation of different frequencies on
      heart rate and heart rate variability in the toads. METHODS: The animals were
      prepared to be models of isolated heart with right vagosympathetic trunks, then
      the nerves stimulated by different frequencies. Collected the electrocardiogram
      of isolated hearts and analyzed the data with HRV software. RESULTS: Since the
      effect of sympathetic nerve had been diminished, vagal stimulation resulted in HR
      being markedly attenuated (P < 0.01), SDNN and RMSSD being significantly
      increased (P < 0.01). There was no significant difference in different levels of
      frequency. Contrast to group control, HR,SDNN and RMSSD each changed clearly. At
      the frequency of 0.2 Hz, HF increased markedly (P < 0.01), and LF/HF decreased
      obviously (P < 0.05) in group P + P. While at the frequency of 0.8 Hz, HF and
      LF/HF were both around the level of pre-stimulation. CONCLUSION: These findings
      suggest that in the certain electrical stimulation frequency range, the effect of
      vagal on HR increases along with the frequency. Without the effect of sympathetic
      nerve, the modulation of vagal to HR and HRV may have different ways.

PMID- 20684289
TI  - [The protective effect of polysaccharide extracted from Laminaria japonica aresch
      on ultramicrostructure of endothelial cell injury induced by adrenaline].

PMID- 20684290
TI  - [Effect of endogenous H2S on platelet L-Arg transport].
AB  - OBJECTIVE: To observe the effect of novel air neuromodulator H2S on platelet
      function of L-Arg transport for discussing H2S of effect on platelet function.
      METHODS: Saturate H2S solution as donate made rat rich platelet plasma and pre
      incubation rat platelet with different density of H2S. To measure the velocity of
      L-Arg transport in platelet by radioactivity technique. RESULTS: At different
      concentrations of H2S (6.25, 12.5, 25, 50, 100 micromol/L), the velocity of L-Arg
      transport was lower than that in control. H2S reduced rapidly the Vmax and
      velocity of L-Arg transport in platelet (P < 0.05) and this effect had no effect
      to Km. CONCLUSION: H2S can affect platelet function by changing rapidly platelet
      L-Arg transport system function.

PMID- 20684291
TI  - [Carbachol improve oxygen dynamic parameters during orally fluid resuscitation of
      a 50% TBSA full-thickness burn in dogs].
AB  - OBJECTIVE: To investigate the effect of carbachol(CAR) on oxygen dynamic
      parameters and hyperlactacidemia during oral fluid resuscitation of burn shock.
      METHODS: Twelve male Beagle dogs were surgically prepared for cannulation of
      carotid and jugular vein, and enterostomy, 24 hours later they were subjected to
      a 50% (total body surface area, TBSA) full-thickness flame injury under a 10-15
      minute anesthesia by IV injection of propofol. The dogs were randomized to
      gastric fluid infusion group (GI group)and gastric fluid infusion plus CAR group
      (GI + CAR). Either a glucose-electrolyte solution(GES) or GES containing CAR (20
      microg/kg) were intragastricly given to animals in GI group or GI+ CAR groups.
      The delivery rate and volume of GES was in accordance with that of Parkland
      formula. Mean arterial pressure (MAP), intestinal mucosal blood flow (IMBF) and
      blood lactic acid were determined, and blood gas analysis evaluated for oxygen
      delivery (DO2), oxygen consumption (VO2) and oxygen uptake (O2ext) at 0, 2, 4, 8,
      24, 48 and 72 hours after injury. RESULTS: The levels of MAP and IMBF markedly
      reduced, and LAC obviously increased in both groups after burn. MAP returned to 0
      h level at 72 h post burn, while IMBF, and LAC were still higher or lower than 0
      h levels. The level of MAP of GI + CAR group was significantly higher than that
      of GI group at 2 h, and those showed no significant differences between two
      groups after then. Carbochol administration led to a markedly higher levels of
      IMBF, and significant lower levels of LAC from 8 h after burn compared with those
      of GI group (P < 0.05 or P < 0.01). The levels of DO2 VO2 and Oext were reduced
      markedly after burn in both groups. At 72 h after burn, DOQ returned to 0 h
      level; while VO2 and Oext though still much lower than 0 h levels. The level of
      DO2. VO2 and Oext of GI + CAR group were significantly higher than those of GI
      group from 8 h after burn (P < 0.05 or P < 0.01). Three of six animals died in
      GI+ CAR group, which was lower than two of six in GI group. CONCLUSION: The
      results indicates that carbachol promotes intragastric fluid resuscitative effect
      of burn shock by increasing oxygen delivery and decreasing hyperlactacidemia.

PMID- 20684292
TI  - [Effects of doxazosin and its enantiomers on serum lipid levels in rabbits fed by
      an atherogenic diet].
AB  - OBJECTIVE: To observe the effects of (-)doxazosin(DOX), (+)DOX and (+/-)DOX on
      serum lipid levels and the mortality rates of the rabbits fed by an atherogenic
      diet. METHODS: Male white New Zealand rabbits were fed by an atherogenic diet for
      4 weeks. 8 rabbits whose serum TC <10 mmol/L were confirmed as normal diet group
      and were fed normally. 40 rabbits whose serum TC >10 mmol/L were randomly divided
      into 4 groups (n=10): atherogenic diet group, atherogenic diet with (-)DOX group,
      atherogenic diet with (+)DOX group and atherogenic diet with (+/-)DOX group,
      which were intraperitoneally injected with (-)DOX, (+)DOX and (+/-)DOX for 9
      weeks respectively. Normal and atherogenic diet group were intraperitoneally
      injected with double distilled water. After 9 weeks administration of (+/
      )doxazosin and its enantiomers, effects of the three agents on serum levels of
      total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol
      (HDL-C) and low density lipoprotein cholesterol (LDL-C) were observed. RESULTS:
      The mortality rate of the rabbits fed by an atherogenic diet for 13 weeks was
      40%, and it was much higher than that of the rabbits fed by a normal diet (10%).
      The mortality rates in the rabbits treated with (-)DOX and (+/-)DOX were lower
      than that in the rabbits fed by a normal diet (10%). Serum LDL-C level of the
      rabbits was increased markedly after 4 weeks of atherogenic diet, and it was
      further increased significantly (P < 0.05 and P < 0.01) during the continued 9
      weeks of atherogenic diet. However, serum LDL-C levels were not further increased
      significantly (P > 0.05) during the continued 9 weeks of atherogenic diet in the
      rabbits treated with (-)DOX, (+)DOX and (+/-)DOX, respectively. CONCLUSION: (
      )DOX and (+/-)DOX increase the survival rate and improve LDL-C disorder mildly in
      the rabbits fed by an atherogenic diet. The improvements in LDL-C induced by (
      )DOX and (+/-)DOX, however, might not be the reason for exploration about the
      increased survival rate in the rabbits fed by an atherogenic diet.

PMID- 20684293
TI  - [Effect of puerarin on action potential and inward rectifier potassium current in
      rat myocardium].

PMID- 20684294
TI  - [Effects of ginkgo biloba extraction on contraction capacity of diaphragm from
      type 2 diabetic rats].
AB  - OBJECTIVE: To investigate the effects of Ginkgo biloba extract (GbE) on the
      activities of energy metabolism enzymes and contraction capacity of diaphragm
      from type 2 diabetic rats. METHODS: Forty SD male rats were randomly divided into
      normal control group (n=10) and model group (n=30). Type 2 diabetes models were
      induced by feeding with high-sucrose-high-fat diet and intraperitoneal injecting
      25 mg/kg streptozotocin. 20 successful models were rearranged to two groups:
      diabetic group and GbE treatment group, 10 rats in each. Then the saline and 8
      mg/(kg x d) of GbE were respectively intraperitoneal injected, once a day
      continuously for 8 weeks. Then diaphragm contractility was assessed using Peak
      twitch tension (Pt), Maximum tetanic tension (P0) and fatigue index (FI) in vitro
      diaphragm strip preparations. Cytochrome oxidase (CCO), lactate dehydrogenase
      (LDH) and succinate dehydrogenase (SDH) in diaphragm were detected and the
      varieties of diaphragm ultrastructure were observed. RESULTS: Compared with
      control group, Pt, P0 and FI in diabetic group decreased significantly (P <
      0.01); the activity of CCO, LDH and SDH in the tissues was more obviously reduced
      than those in control group (P < 0.01). The ultrastructure in diabetic group
      under electron microscope indicated that diaphragm mitochondrions swelled and
      degenerated. The above changes were inhibited by GbE. CONCLUSION: GbE can enhance
      contraction capacity of diaphragm from type 2 diabetic rats by increasing the
      aerobic oxidation capacity, glycolytic capacity and the function of respiratory
      chain.

PMID- 20684295
TI  - [Statistical analysis of articles in "Chinese journal of applied physiology" from
      1999 to 2008].
AB  - OBJECTIVE: To evaluate the academic level and influence of "Chinese Journal of
      Applied Physiology" through statistical analysis for the fund sponsored articles
      published in the recent ten years. METHODS: The articles of "Chinese Journal of
      Applied Physiology" from 1999 to 2008 were investigated. The number and the
      percentage of the fund sponsored articles, the fund organization and the author
      region were quantitatively analyzed by using the literature metrology method.
      RESULTS: The number of the fund sponsored articles increased unceasingly. The
      ratio of the fund from local government significantly enhanced in the latter five
      years. Most of the articles were from institutes located at Beijing, Zhejiang and
      Tianjin. CONCLUSION: "Chinese Journal of Applied Physiology" has a fine academic
      level and social influence.

PMID- 20684296
TI  - [Investigations on the audible third heart sound subjects under stress state].

PMID- 20684297
TI  - [Heavy metal absorption, transportation and accumulation mechanisms in
      hyperaccumulator Thlaspi caerulescens].
AB  - Thlaspi caerulescens, the famous model plant of heavy-metal hyperaccumulator, can
      uptake and accumulate large amount of heavy metals in its above-ground part of
      the plants. However, the very low biomass in Thlaspi caerulescens makes this
      plant unfit for direct application in phytoremediation. In recent years, there
      are many reports about the physiological and molecular characterization of
      Thlaspi caerulescens under heavy metals stresses, including absorption, transport
      and intracellular detoxification processes (e.g., chelation and
      compartmentation). Research teams have conducted many studies of chelators in
      plants, such as organ acid, amino acid, phytochelatins, metallothioneins and
      nicotianamine, and so on. Several transport protein families, such as Zinc
      Regulated Protein, Cation Diffusion Facilitator, Natural Resistance and
      Macrophage Protein and Heavy Metal ATPase, play important role in short/long
      distance transport in the plant. In this review, we summarize the current
      knowledge of the physiological and molecular mechanisms of heavy metals
      accumulation in Thlaspi caerulescens, with particular emphasis on the roles of
      transporters and chelatins in modulating plant heave-metal-stress responses.

PMID- 20684298
TI  - [Functions of late embryogenesis abundant proteins in desiccation-tolerance of
      organisms: a review].
AB  - Late embryogenesis abundant (LEA) proteins are well associated with the
      desiccation tolerance in organisms. LEA proteins are categorized into at least
      seven groups by virtue of similarities in their deduced amino acid sequences.
      Most of the LEA proteins have the characteristics of high hydrophilicity and
      thermo-stability. The LEA proteins are in unstructured conformation in aqueous
      solution. However, they adopted amphiphilic alpha-helix structure during
      desiccation condition. LEA proteins are localized to the different organelles in
      the cells, i.e. cytoplasm, endoplasmic reticulum, mitochondria and nucleus. The
      multi-functional capacity of LEA proteins are suggested, as protein
      stabilization, protection of enzyme activity, membrane association and
      stabilization, antioxidant function, metal-ion binding or DNA protection, etc.
      Here, we review the structural and functional characteristics of LEA proteins to
      provide a reference platform to understand their protective mechanisms during the
      adaptive response to desiccation in organisms.

PMID- 20684299
TI  - [Product safety analysis of somatic cell cloned bovine].
AB  - Somatic cell cloning (nuclear transfer) is a technique through which the nucleus
      (DNA) of a somatic cell is transferred into an enucleated oocyte for the
      generation of a new individual, genetically identical to the somatic cell donor.
      It could be applied for the enhancement of reproduction rate and the improvement
      of food products involving quality, yield and nutrition. In recent years, the
      United States, Japan and Europe as well as other countries announced that meat
      and milk products made from cloned cattle are safe for human consumption. Yet,
      cloned animals are faced with a wide range of health problems, with a high death
      rate and a high incidence of disease. The precise causal mechanisms for the low
      efficiency of cloning remain unclear. Is it safe that any products from cloned
      animals were allowed into the food supply? This review focuses on the security of
      meat, milk and products from cloned cattle based on the available data.

PMID- 20684300
TI  - [CpG island methylation patterns and expressions of H19 gene in cloned fetus of
      goat].
AB  - The aberrant epigenetic reprogramme is an important cause for abnormal
      development of nuclear transfer embryos. The objective of this study was to
      investigate the CpG island methylation profiles and relative expression levels of
      H19 gene in different tissues of cloned goat fetus. We detected liver, placenta,
      kidney, lung and heart in the dead cloned goat fetus and the age-matched normal
      goat fetus (control) by using bisulfite sequencing and real time PCR. Results
      indicated that methylation levels of the fifth CpG island of H19 gene in dead
      cloned goat fetus was significant high compared with that in the control in
      placenta (70% vs 49.41%, P < 0.05), and relative expression levels of H19 gene
      was significant low compared with that in the control (883.3 vs 1 264.5, P <
      0.05). Reversely, the methylation levels was significant low compared with that
      in the control in lung (63.53% vs 88.24%, P < 0.05), and relative expression
      levels was significant high compared with that in the control (1 003.4 vs 515.5,
      P < 0.05). The differences of others groups were insignificant (P > 0.05).
      Results showed the abnormal DNA methylation proflies of H19 gene occurred in some
      tissues of cloned goat fetus, which affected normal expression levels of H19
      gene, indicating that aberrant DNA methylation reprogramme may be one of the
      important factors for the death of cloned animals.

PMID- 20684301
TI  - [Genetic diversity in goat breeds based on microsatellite analysis].
AB  - Fluorescence PCR was applied to investigate the genetic diversities of 9
      indigenous Chinese goat breeds and 1 exotic breed with 10 microsatellite DNA
      markers recommended by the Food and Agriculture Organization of the United
      Nations and the International Livestock Research Institute of Animal Genetics,
      which provide data for the preservation and utilization of indigenous goat breeds
      genetic resource. We found that the 7 breeds were high polymorphic while 3 breeds
      were moderate polymorphic. We also detected 119 alleles, and the effective allele
      number ranged from 1.4641 to 9.2911. The average heterozygosity of loci and
      breeds respectively varied from 0.2618 to 0.7672 and from 0.5196 to 0.7024. As
      well as SRCRSP23 site and Hexi cashmere goat had the highest average
      heterozygosity. Then we analyzed the phylogenetic trees (NJ and UPGMA), and found
      both of them were generally in accordance with their original breeding history
      and localities.

PMID- 20684302
TI  - [Recombinant Vp2 protein of infectious bursal disease virus AH1 strain expressed
      in insect cells: a vaccine candidate].
AB  - Protective immune response of the available IBD vaccine is insufficient to fully
      protect against the prevailing strain of the infectious bursal disease virus
      (IBDV). Such a vaccination escape IBDV field isolate idenfied from Anhui province
      of China in December 2007, where IBD broke out at 2 weeks post vaccination. The
      IBDV vp2 gene was cloned into pFastBacHTA donor plasmid, followed by generation
      of the recombinant bacmid DNA pBac-VP2. The latter was used to transfect insect
      cell Sf9 with Lipofectamine to produce recombinant baculovirus vBac-VP2. The Sf9
      cells infected with vBac-VP2 were stained positive against IBDV antibody using
      the indirect immunofluorescence assay (IFA), which was also confirmed by the
      detection of IBDV Vp2 protein in the infected Sf9 cells by IBDV sandwich ELISA.
      Western blotting revealed that the calculated protein of approximately 53 kDa was
      in the expressed in the insect cells. Moreover, virus-like particles (VLPs) and
      "inclusion body-like"structure in the infected Sf9 cells were observed under
      electron microscopy. We further developed an indirect ELISA for the detection of
      the IBDV antibodies, which was specific and sensitive. In addition, the lysates
      of vBac-VP2 infected cells was used to immunize 2-week-old SPF chickens, followed
      by challenging with the virulent IBDV, the survival rate was 30% at 14 days post
      primary immunization, however, the survival rate was 100% at 14 d after the
      booster vaccination. The ELISA antibody titers was up to 3.2 x 10(3) and
      neutralization antibody titer was 2536, significantly higher than those of one
      shot vaccination, 8 x 10(2) and 1106, respectively. The immunized chickens did
      not show any clinical signs and histopathological changes of infection in 7-days
      trial time. The bursa/body-weight ratios were higher than those of the
      unimmunized control (P < 0.05). The virus-like-particle recombinant Vp2 protein
      expressed in insect cells promises to be a novel subunit vaccine and diagnostic
      reagent candidate for IBDV.

PMID- 20684303
TI  - [Impact of fermentation system initial status on oscillations in very high
      gravity ethanol continuous fermentation process and analysis of fermentation
      efficiency improvement].
AB  - Prior research reported the oscillatory behavior characterized by long period and
      high amplitude during high gravity continuous ethanol fermentations at the
      dilution rate of 0.027 h(-1). In this paper, high gravity continuous ethanol
      fermentations using Saccharomyces cerevisia at different dilution rates were
      carried out. Similar oscillations were observed when the dilution rate was
      switched to 0.04 h(-1). Both oscillatory and steady processes can be achieved at
      dilution rates of 0.027 or 0.04 h(-1), which depends on the initial status of the
      fermentation system. However, compared to steady process at the same dilution
      rate of 0.04 h(-1), the average residual sugar concentration was lowered by 14.8%
      for the oscillatory process, while the average ethanol concentration and
      productivity were increased by 12.6% and 12.3%, respectively. Further
      investigation revealed that besides the lag time, oscillatory processes were
      different from steady ones in kinetics because a higher specific growth rate can
      be achieved at the same residual sugar and ethanol concentrations (increased by
      53.8% in average).

PMID- 20684304
TI  - [Expression of phytase gene phyA in Yarrowia lipolytica po1h].
AB  - Using the polymmerse chain reaction (PCR), we amplified the phytase gene phyA
      from Pichia pastoris GS115-phyA in Aspergillus niger NRRL3135 without the signal
      peptide sequence and intron sequence,. Then, it was cloned into pINA1297 vector
      to generate a recombinant vector of pINA1297-phyA. pINA1297-phyA was linearized
      and transformed into Yarrowia lipolytica po1h by the lithium acetate method. The
      positive transformants were obtained by YNB(casa) and PPB plates, after induced
      in YM medium at 28 degrees C for 6 day. The activity of the expressed phytase
      phyA reached 636.23 U/mL. The molecular weight of the enzyme was 130 kDa measured
      with SDS-PAGE analysis, whereas its molecular size reduced to 51 kDa after
      deglycosylation which is correspond with theoretical value. The enzymatic
      analysis of the recombinant phytase phyA revealed its optimal pH and temperature
      was 5.5 and 55 degrees C, which had high activity after incubated in pH ranged
      from 2.0 to 8.0 for 1 h. Moreover, its activity remained 86.08% after exposure to
      90 degrees C for 10 min. It also was resistant to pepsin or trypsin treatment.

PMID- 20684305
TI  - Construction of a Pichia pastoris recombinant strain capable of over-expressing
      phytase and endoglucanase.
AB  - Both phytase and endoglucanase are additives in feed for mono-gastric animal
      known for their effects. Recombinant vector pPICZalpha-EG was constructed and
      transformed to GS115-phyA, a Pichia pastoris strain that had integrated with
      phytase gene, generating GS115-phyA-EG. Both phytase and endoglucanase activities
      in the supernatant were determined after methanol induction of GS115-phyA-EG.
      Phytase and endoglucanase activity reached 39.4% and 56.2% activity compared to
      GS115-phyA and GS115-EG, respectively. Properties of the mixed enzyme suggest
      that the optimal temperature and pH value be 55 degrees C and 5.5 respectively.
      Both phytase and endoglucanase showed greater than 80% activity across
      temperature ranges 45 degrees C to 55 degrees C and pH ranges 4.5 to 5.5.
      Expressing more than one enzyme in one system could save time and money during
      induced expression, and the mixed enzyme might apply for treating forge before
      feeding with poultry.

PMID- 20684306
TI  - [Enhancing stability of Trichoderma reesei xylanase (XYN II) by site-directed
      mutagenesis].
AB  - We engineered a disulphide bridge between two adjacent double-layered beta-sheet
      at the N-terminal region of Trichoderma reesei endo-1,4-beta-xylanase II(XYN II)
      by site-directed mutagenesis. The native xylanase XYN-OU and the mutated xylanase
      XYN-HA12 (T2C, T28C and S156F) were separately expressed in Pichia pastoris. Both
      xylanases were purified and characterized. The optimum temperature of XYN-HA12
      was increased from 50 degrees C to 60 degrees C, relative to XYN-OU. At 70
      degrees C, the halftime of inactivation for XYN-OU and XYN-HA12 were 1 min and 14
      min, respectively. The optimum pH of XYN-HA12 was 5.0, similar to XYN-OU.
      However, XYN-HA12 could retain over 50% activity from pH 3.0 to 10.0 at 50
      degrees C for 30 min. As for XYN-OU, it could retain over 50% activity from the
      pH value 4.0 to 9.0 at 50 degrees C in 30 min. The result of the mutated xylanase
      indicated that constructed disulphide bridge could improve its thermostability at
      relatively higher temperature.

PMID- 20684307
TI  - [Transformation of enhanced green fluorescent protein gene in Paecilomyces
      lilacinus mediated by Agrobacterium tumefaciens].
AB  - The main aim of this study was to transform the enhanced green fluorescent
      protein gene (egfp) into biocontrol fungus Paecilomyces lilacinus strain 9410. We
      constructed the expression vector pUPNGT of the fusion gene nptII-egfp using
      pcDNA3.1(-) as a helper plasmid. The egfp gene was then transformed into P.
      lilacinus strain 9410 via Agrobacterium tumefaciens-mediated transformation. PCR
      and Southern blotting analysis showed that the egfp gene was integrated into the
      genomes of the tested transformants and the integration manner was single-copy.
      The transformants could generate green fluorescence when they were excited by 488
      nm blue laser. These results indicated that the egfp gene had been successfully
      transformed into P. lilacinus 9410 and expressed in the tested transformants. Our
      work may provide a new approach to assess environmental safety and practical
      biocontrol efficacy ofP. lilacinus under different conditions.

PMID- 20684308
TI  - [Intergenus somatic hybridization between Alhagi pseudalhagi and Astragalus cicer
      by electroporation].
AB  - We obtained intergenus somatic hybrid between Alhagi pseudalhagi and Astragalus
      cicer by using electroporation. Agrobacterium rhizogenes A4-transformed A.
      pseudalhagi protoplasts were treated with iodoacetamide so that they were unable
      to sustain divisions. A. cicer protoplasts were isolated from a methionine
      resistant mutant and did not survive in the medium without plant growth
      regulator. The intergenus somatic hybrid cells were selected based on
      physiological complementation between the two parents. We optimized some
      parameters of electroporation, such as direct current impulse, alternating
      current impulse and the impulse number. We identified ten hybrid clones by
      morphological observation, checking the chromosome numbers, isoenzyme analysis
      and random amplified polymorphic DNA analysis, and obtained regenerated plantlets
      from three hybrid clones.

PMID- 20684309
TI  - [Transplantation of atrial natriuretic peptide-expressing fibroblasts reduces
      blood pressure and increases urine volume in spontaneously hypertensive rats].
AB  - To investigate the potential of gene therapy for the treatment of chronic
      diseases such as hypertension, chronic heart failure, and chronic renal failure,
      we established the neonatal rat fibroblast line engineered to secrete the mutant
      human atrial natriuretic peptide (mhANP), and then transplanted the cell line
      into young spontaneously hypertensive rats (SHR) subcutaneously. We found that a
      single transplantation of the cell line caused an obvious rise in the
      concentration of mhANP in serum 7 d after transplantation ((135 +/- 8) vs (106 +/
      7) pg/mL, P < 0.01). The animals' blood pressure in test group was always
      remarkably lower than that of empty vector group within 42 d after
      transplantation, even though the blood pressure in all groups was constantly
      increasing in the process of ontogeny ((175 +/- 10) mm Hg vs (189 +/- 12) mm Hg,
      P < 0.05). A maximal blood pressure reduction of 33 mm Hg ((157 +/- 9) mm Hg vs
      (124 +/- 112) mm Hg, P < 0.01) was observed 14 d post cell transplantation. There
      was a marked increase in urine volume in test group from second week after
      treatment beginning ((5.9 +/- 0.7) mL/6 h vs (4.3 +/- 0.8) mL/6 h, P < 0.01) and
      the effect lasted 14 d ((6.1 +/- 1.1) mL/6 h vs (4.0 +/- 0.8) mL/6 h, P < 0.01),
      however the statistical difference in concentration of K+ and Na+ in serum and
      urine was not observed. The results suggested that subcutaneous implantation of
      fibroblasts-expressing mhANP significantly reduced blood pressure in young SHR
      during the period of ontogeny and efficiently improved their renal function and
      the somatic gene transfer of mhANP may have potential value in the treatment of
      human chronic diseases such as hypertension, chronic heart failure, and chronic
      renal failure.

PMID- 20684310
TI  - [Immunological evaluation of vector-expressed M2 and HA genes of H5N1 influenza
      virus in mice].
AB  - We developed vectors expressing two antigen of H5N1 influenza virus. Based on the
      human H5N1 avian influenza virus strain A/Anhui/1/2005 isolated in China, we
      amplified the matrix protein 2 (M2) and Hemagglutinin (HA) genes by PCR and
      subcloned them into pStar vector to construct two genes co-expressing recombinant
      DNA vaccine pStar-M2/HA. After transfection of 293 cells with the plasmid, we
      confirmed with indirect immunofluorescence assay (IFA) that M2 and HA genes
      cloned on plasmid pStar co-expressed successfully. Using Ad-Easy adenovirus
      vector system, by homologous recombination in bacteria and packaging in 293
      cells, we constructed two recombinant adenoviruses, namely Ad-M2 and Ad-HA. After
      infection of 293 cells with the recombinant adenoviruses, we confirmed with IFA
      that M2 and HA genes cloned into adenoviruses expressed successfully. We then
      combined the recombinant DNA vaccine and adenoviral vector vaccines in
      immunization of BALB/c mice with a prime-boost regime. On day 0 and day 28, we
      immunized the mice with DNA vaccine and on day 14 and day 42, with recombinant
      adenovirus vaccines. We took blood samples before each injection and 14 days
      after the final injection. On day 56, we collected splenocytes from the mice.
      ELISA and hemagglutination inhibition (HI) assay showed that the vaccines
      successfully induced specific IgG antibodies against HA protein in serum of the
      immunized mice. ELISPOT confirmed that the vaccines successfully induced the
      special cellular immune response to M2 and HA protein of H5N1 influenza virus.
      The study on combined immunization with M2 and HA genes provided basis for
      development of novel influenza vaccine.

PMID- 20684311
TI  - [Eucaryotic expression and bioactivity analysis of the recombinant HSV-gD1].
AB  - Envelope proteins of herpes simplex virus (HSV) plays a vital role not only in
      the infection process of adsorption and invasion but also in the stimulation to
      the organism that gives rise to immune response. Among the envelope proteins,
      glycoprotein D (gD), which can induce specific immune response, are the primary
      targets of humoral and cellular immunity of the host. In order to analyze the
      antigenicity and immunogenicity of HSV-gD1, we chemically synthesized the
      extracellular domain fragment gene of gD1, cloned it into eucaryotic expression
      vector pCEP4, and transfected the HEK293 cells with the recombinant vector. Then
      we identified the recombinant protein by Western blotting, and detected
      antigenicity of the protein by ELISA. Finally, we used the purified gD1 protein
      to immunize Kunming mice in 1, 3, 5 weeks, and collected antiserum in 3, 5 and 7
      weeks. We titrated the sera for the detection of anti gD1 using an ELISA assay.
      Gene sequencing analysis demonstrated that the recombinant plasmid pCEP4-gD1 was
      constructed successfully. Western blotting analysis indicated one major protein
      band, which molecular weights is approximate 46 kDa corresponding to the
      truncated forms of gD1 protein, was observed. ELISA assay showed that the
      expressed recombinant protein gD1 had good antigenicity. After the third
      immunization, antibody titer of the mouse anti-gD1 was at least 5 x10(3). The
      successful expression of the recombinant protein gD1, which can induce humoral
      immune response, lays a foundation for serological diagnosis and vaccine study of
      HSV.

PMID- 20684312
TI  - [Expression of human angiotensin converting enzyme-C domain in Pichia pastoris].
AB  - Angiotensin I-converting enzyme (ACE, EC3.4.15.1) plays an important role in
      regulating blood pressure. The C-domain of ACE has been identified as the main
      catalytic site of angiotensin I cleavage in vivo. The ACE gene fragment of the C
      domain was amplified by PCR and cloned into the pPIC9K secretory expression
      plasmid. The recombinant plasmid was transformed into Pichia pastoris strain
      GS115. Positive clones were selected and subject to electroporation. Antibiotic
      G418 was used for the screening of multicopy inserts. After optimization of the
      expression system, the protein yield reached 0.5 g/L by flask-shaking culture
      fermentation, and enzyme activity reached 7.178 U/mL in the fermentation
      supernatant. The purity of the target protein obtained was 97% after Ni+ affinity
      chromatography. Enzyme inhibitory activity assay using Captopril showed that it
      is promising to use ACE-C domain as new generation of target for screening ACE
      inhibitor antihypertensive drugs.

PMID- 20684313
TI  - [Overexpression of Nanog gene in mouse mesenchymal stem cells and its influence
      on NF-kappaB expression].
AB  - The expression of NF-kappaB is considered to be involved in the progress of
      neurodegeneration. It has been reported that Nanog can suppress the expression of
      NF-kappaB. To inspect and verify this finding, we constructed lentivirus (LV)
      vector that overexpressed the Nanog gene, infected mouse mesenchymal stem cells
      (mMSCs), and examined the influence of Nanog overexpression on NF-kappaB gene
      expression. The plasmid pNL-Nanog-IRES2-EGFP was constructed by double digestion
      and genetic recombination. Sequencing results confirmed that our cloned Nanog
      gene in the PNL-Nanog-IRES2-EGFP plasmid was consistent with the sequence
      reported in the GenBank. The three plasmids: pNL-Nanog-IRES2-EGFP, HELPER, and
      VSVG were cotransfected into 293T cells to produce LV particles. After co
      transfection of the three lentiviral plasmids, green fluorescence was observed
      confirming successful transfection. The mMSCs were infected by the LV and the
      expression of Nanog was then also verified by the presence of green fluorescence.
      Nanog expression levels in the mMSCs were examined using Western blotting.
      Expression of NF-kappaB was also examined using RT-PCR and Western blotting, and
      in addition with fluorescent microscope after immunocytochemical staining. The
      levels of Nanog protein expression in Nanog-mMSCs were significantly increased,
      and the levels of NF-kappaB mRNA and protein expression in Nanog-infected mMSCs
      were significantly lower than those of Mock-mMSCs and the mMSCs control groups.
      Our findings suggest that mMSCs genetically modified to overexpress Nanog can
      lead to the suppression of NF-kappaB expression. This suppression of NF-kappaB
      could have important implications for the treatment of neurodegeneration, and
      hence further scientific investigations of these interactions will have
      significant impact on future clinical attempts to attenuate disease progression.

PMID- 20684314
TI  - [A novel packaging system of recombinant AAV5/5 vector].
AB  - We developed a scalable AAV5/5 vector packaging system by using replication
      competent recombinant herpes simplex type 1 virus as helper virus. The fragment
      containing rep and cap genes of AAV5 was inserted into the non-necessary gene
      (UL2) of HSV1 genome, resulting in the helper virus rHSV1-rep5cap5. An AAV5/5
      vector pAAV5neo carrying two AAV5 ITRs was constructed by inserting a neo gene
      expression cassette into the plasmid backbone of pAV5CMV-GFP. pAAV5neo-EGFP was
      constructed by inserting EGFP gene into pAAV5neo. BHK21 cell was transfected with
      pAAV5neo-EGFP and cultured in the presence of G418. EGFP expression positive
      monoclonal cells were picked up, and one that produced rAAV5/5-EGFP with the
      highest efficiency under the help of rHSV1-rep5cap5 was chosen as the production
      cell line named as C020. rAAV5/5-EGFP was produced by infecting C020 cells with
      rHSV1-rep5cap5, and crudely purified by our previous method of 'chloroform
      treatment-PEG8000/NaCl precipitation- chloroform extract'. rAAV5/5-EGFP
      preparation with high purity was obtained by ultrafiltration with molecular
      weight cut-off value of 100 kDa. SDS-PAGE stained with Coomassie brilliant blue
      R250 showed clearly specific pattern of three bands of AAV capsid proteins.
      rAAV5/5-EGFP was also assayed using negative stain transmission electron
      microscopy and the majority of the virus particles were found solid. About 30%
      green fluorescent cells could be seen after infecting HEK293 cells with rAAV5/5
      EGFP 24 h at 1 x 10(5) vg/cell. In conclusion, we have established an efficient
      AAV5/5 vector production system and could produce recombinant AAV5/5 virus in
      large amounts for gene therapy research.

PMID- 20684315
TI  - [Characterization of protein secretion based on structural fusion degree].
AB  - Selection of suitable signal peptides is an important factor for efficient
      secretion of heterologous proteins. We defined structural fusion degree (SFD) as
      the compatibility degree of target proteins and signal peptides by a
      bioinformatics approach. We mathematically analyzed the interaction of fused
      signal peptides and adjacent residues of proteins, and proposed a mathematical
      model of extended signal region and the protein. SFD Features was extracted from
      this model to characterize the secretability of heterologous proteins. Simulation
      tests showed that SFD features can effectively discriminate high secretory
      proteins from poor ones in the host Bacillus subtilis. Results from this research
      will be useful in signal peptide selection and have a better guiding significance
      for the optimization of heterologous protein secretion.

PMID- 20684316
TI  - [Y chromosome microdeletion and male infertility: past, present and future].
AB  - The spermatogenesis failure with a genetic defect is one of the major causes of
      male infertility. The Y chromosome is considered a lack of important functional
      genes. It was the discovery of the sex determining region Y that rekindled
      scientists'attention to the Y chromosome. The successful sequencing of the Y
      chromosome uncovered its actual structure and the molecular base of its
      microdeletion. Of the 220 Y chromosome genes (104 coding genes, 111 pseudogenes,
      and 5 other uncategorized genes), 16 coding genes have been found in the
      azoospermia factor region (AZF) and related with male fertility. To date, more
      than 12 Y chromosome microdeletions have been discovered in the AZF region. The
      amplicons regions in the Y chromosome are the genetic base of microdeletion
      occurrence. The Y chromosome microdeletions in the AZF region have been
      identified as a relatively common cause of male infertility and diagnosed by
      multiplex PCR in the clinical laboratory. Genomics has brought many
      revolutionized tools beneficial for better understanding the genetics of mal
      infertility and defining the role of the Y chromosome gene in spermatogenesis.

PMID- 20684317
TI  - [Murine model of busulfan-induced spermatogenesis regeneration: a quantitative
      evaluation].
AB  - OBJECTIVE: To quantitatively evaluate the murine model of spermatogenesis
      regeneration induced by two-dose busulfan injection. METHODS: Fifty-four male
      mice were randomly divided into a control and two model groups of equal number,
      the former treated by two-dose intraperitoneal injection of 50% DMSO solution at
      10 ml/kg, and the latter by that of busulfan at 10 mg/kg and 15 mg/kg
      respectively to establish spermatogenesis regeneration models, both at the
      interval of 24 days between the two doses. Spermatogenesis in seminiferous
      epithelia was evaluated by Johnsen score, and the expressions of GATA-4 and GDNF
      mRNA in Sertoli cells were detected by real time quantitative PCR at 3, 4 and 8
      weeks after the treatment. RESULTS: Johnsen score kept stable in the control
      group at all stages (P > 0.05), but higher than in the model groups at 3 and 4
      weeks (P < 0.01). It was lower in the 15 mg/kg than in the 10 mg/kg model group
      at 4 and 8 weeks (P < 0.01) , and than in the control group at 8 weeks (P <
      0.05), but had no significant difference between the 10 mg/kg and the control
      groups (P > 0.05). Nor did the expression of GATA-4 mRNA in Sertoli cells show
      any significant difference among the three groups at different stages after the
      treatment (P > 0.05), and that of GDNF mRNA at different stages in the control
      group (P > 0.05). Compared with the controls, the level of GDNF mRNA in Sertoli
      cells was significantly higher at 3 weeks but lower at 4 weeks in the model
      groups (P < 0.01), and lower in the 15 mg/kg group (P < 0.01) and comparable in
      the 10 mg/kg group at 8 weeks (P > 0.05); and it was lower in the 15 mg/kg than
      in the 10 mg/kg group at all stages (P < 0.01). CONCLUSION: Two-dose
      intraperitoneal injection of 10 mg/kg busulfan at the interval of 24 days is an
      optimal option for the establishment of a murine model of spermatogenesis
      regeneration. Higher dose of busulfan may induce deficient expression of GDNF in
      Sertoli cells and result in incomplete restoration of spermatogenesis.

PMID- 20684318
TI  - [Expression of rat annexin 5 and its effect on human sperm motility in vitro].
AB  - OBJECTIVE: Gonadotropin releasing hormones (GnRH) regulate the expression of
      annexin 5 in Leydig cells, and annexin 5 is supposed to be a signal molecule in
      regulating testosterone secretion. This study aimed to investigate the function
      of annexin 5 in male reproduction by observing its effect on human sperm motility
      in vitro. METHODS: The encoding sequence of rat annexin 5 was chemically
      synthesized and inserted into the HIS fusion expression vector pET28a. The
      expression of the fusion protein HIS-annexin 5 was induced by isopropyl-beta-D
      thiogalactoside (IPTG) under the control of the T7 promoter, and the products
      were purified by affinity chromatography. The anticoagulant activity of annexin 5
      was determined by the modified activated partial thromboplastin time (APTT) test.
      Semen samples from 15 donors were assigned to a control and an annexin 5 group,
      the latter treated with recombinant annexin 5 at the concentration of 10(-8)
      mol/L. Sperm motility and the percentage of grade a + b sperm were measured by
      computer-assisted semen analysis (CASA) after 20 and 60 min exposure, and the
      sperm ascending experiment was done after 20 min treatment. RESULTS: The product
      of the synthesized target gene was 947 bp in length, and the inserted sequence
      corresponded to the published encoding sequence of rat annexin 5. The plasmid
      pET28a-annexin 5 was transformed into E. coli BL21(DE3) and IPTG induced a fusion
      protein with a relative molecular weight of about 36,000, a purity of 95% and a
      high anticoagulant activity. Compared with the control group, sperm motility and
      the percentage of grade a + b sperm were increased by 40% (P < 0.01) and 21% (P <
      0.01), respectively, after 20 min treatment with annexin 5, but neither showed
      any significant improvement after 60 min. The sperm ascending altitude was
      remarkably elevated after annexin 5 treatment, with extremely significant
      difference from the control group (37.84 +/- 6.35 vs. 49.5 +/- 12.27, P < 0.01).
      CONCLUSION: An annexin 5 recombinant expression vector was successfully
      constructed. The protein annexin 5 can be efficiently expressed in E. coli and
      effectively improve human sperm motility in vitro.

PMID- 20684319
TI  - [Differential expressions of the receptor for advanced glycation end products in
      prostate cancer and normal prostate].
AB  - OBJECTIVE: To study the differential expressions of the receptor for advanced
      glycation end products (RAGE) in the tissues of prostate cancer and normal
      prostate, and to find the role of RAGE in the pathogenesis of prostate cancer.
      METHODS: We collected the tissue of prostate cancer and that of normal prostate
      from the same patient, and compared the differential expressions of RAGE at the
      tissue, protein and mRNA levels between prostate cancer and normal prostate
      tissues of 10 patients by immunohistochemistry, Western blot and real-time
      quantitative PCR. RESULTS: Immunohistochemistry exhibited a significantly higher
      expression of RAGE in the prostate cancer tissue than in the normal prostate
      tissue; Western blot showed that the RAGE protein expression was 2.13 times
      higher in the former than in the latter (P < 0.05); and real-time quantitative
      PCR revealed the RAGE mRNA expression of the former to be 4.2 times that of the
      latter (P < 0.05). CONCLUSION: RAGE may play an important role in the
      pathogenesis and progression of prostate cancer.

PMID- 20684320
TI  - [Induction of prostate cancer-specific CTLs with dendritic cells pulsed by
      different types of tumor antigens].
AB  - OBJECTIVE: To study the effectiveness of freeze-thaw antigens and acid eluted
      peptide antigens extracted from tumor cell-pulsed dendritic cells (DC) in
      inducing prostate cancer-specific cytotoxic T lymphocytes (CTL) in vitro.
      METHODS: Tumor antigens were extracted from the prostate cancer cell line PC-3
      with the repeated freeze-thaw and weak acid elution methods. Peripheral blood
      mononuclear cells were cultured with recombinant human GM-CSF and IL-4 for
      inducing DCs in vitro. Then the DCs were pulsed with the two kinds of prostate
      cancer tumor antigens respectively and cultured with T cells for inducing CTLs.
      The activity of the tumor-specific CTLs were detected by LDH release assay.
      RESULTS: The protein content in the tumor antigens obtained from PC-3 (2 x 10(7))
      by citric acid-phosphate buffer elution and that by the repeated freeze-thaw
      method were (212.2 +/- 7.9) microg and (963.0 +/- 25.3) microg, respectively. The
      two kinds of prostate cancer antigens-pulsed DCs had a significant role in
      inducing the PC-3 cell-specific CTLs, and the CTLs induced by acid-eluted peptide
      antigen-pulsed DCs exhibited an even more significant tumor-specific cytotoxicity
      than those induced by repeated freeze-thaw ([60.4 +/- 5.52]% vs. [43.7 +/-
      4.11]%, P < 0.01). CONCLUSION: Both the weak acid elution and repeated freeze
      thaw methods for extracting prostate cancer antigens can be used for in vitro
      sensitization of DCs. The DCs pulsed by either of the two kinds of antigens can
      activate CTLs, and the antigens extracted by weak acid elution are even more
      effective.

PMID- 20684321
TI  - [Total PSA, PSA density and biopsy Gleason score in predicting the pathologic
      stage of prostate cancer].
AB  - OBJECTIVE: To evaluate the roles of total prostate specific antigen (tPSA), PSA
      density (PSAD) and biopsy Gleason score in predicting the pathologic stage of
      prostate cancer. METHODS: We retrospectively analyzed the clinical data of 124
      cases of pathologically confirmed prostate adenocarcinoma, and divided them into
      Groups A (n=48) and B (n=76) based on the results of bone scanning, CT, MRI,
      tPSA, PSAD and postoperative biopsy Gleason score, the former with extraprostatic
      infiltration or distant metastasis, while the latter without. We compared the
      above parameters between the two groups, screened the main factors that
      influenced the pathologic staging of prostate cancer by multivariate logistic
      regression analysis, and appraised the value of each of the parameters in
      predicting the pathologic stage of prostate cancer with a relative operating
      characteristic (ROC) curve. RESULTS: The tPSA level and biopsy Gleason score were
      significantly higher in Group A than in B (P < 0.05). Multivariate logistic
      regression analysis showed that only tPSA could predict the pathologic stage of
      localized prostate cancer. The ROC curve exhibited that the combined use of tPSA
      and Gleason score had a better predicting value than other parameters (Gleason
      score + tPSA > tPSA > PSAD + tPSA + Gleason score). CONCLUSION: Total PSA remains
      a valuable predictor of the pathologic stage of prostate cancer, and its
      combination with Gleason score can further improve the predictive accuracy and
      contribute much to the treatment and prognosis of the disease.

PMID- 20684322
TI  - [L-carnitine: safe and effective for asthenozoospermia].
AB  - OBJECTIVE: One of the important reasons for male infertility is
      asthenozoospermia, for which there is no specific cure for the time being. The
      authors explored the clinical effect of L-carnitine for infertile males with
      asthenozoospermia. METHODS: A total of 135 patients with asthenozoospermia were
      randomly divided into Groups A (n = 68) and B (n = 67), the former treated with L
      carnitine (2 g/d) and vitamin E, while the latter with vitamin E only, both for 3
      months. All the patients received semen analyses before and after the treatment,
      and were observed for adverse effects. The pregnancy rates of their wives were
      recorded. RESULTS: Group A showed a significantly increased percentage of forward
      motile sperm after the treatment (45.4% +/- 11.1%) as compared with pretreatment
      (28.6% +/- 9.2%) (P < 0.01), but no statistically significant differences were
      found in sperm density and the percentage of the sperm of normal morphology (P >
      0.05). The rate of pregnancy was significantly higher in Group A (31.1%) than in
      B (3.8%) after the treatment (P < 0.01). No adverse events were found during the
      treatment. CONCLUSION: L-carnitine, capable of significantly improving sperm
      motility and raising the rate of pregnancy, is a safe and effective therapeutic
      option for asthenozoospermia.

PMID- 20684323
TI  - [Inhibitory effect of TRPV6 silencing on prostate cancer cell line LNCaP in
      vitro].
AB  - OBJECTIVE: To explore the effects of the TRPV6 gene silencing by small
      interfering RNA (siRNA) on the proliferation, cell cycle and apoptosis of human
      prostate cancer LNCaP cells. METHODS: We constructed two siRNA sequences (siTRPV6
      1 and siTRPV6-2) targeting the TRPV6 gene and then transfected them into LNCaP
      cells mediated by liposome. The transcription of TRPV6 mRNA was detected by RT
      PCR, and the effects of siRNA on the proliferation, cell cycle and apoptosis of
      the LNCaP cells were determined by MITT and flow cytometry. RESULTS: Both siTRPV6
      1 and siTRPV6-2 significantly suppressed the expression of TRPV6 mRNA in the
      LNCaP cells, and the expression was decreased with the extension of time, by 73
      and 77% respectively at 72 h after transcription with siTRPV6-1 and siTRPV6-2 as
      compared with the blank control group (P < 0.01). The proliferation inhibition
      rates were the highest (34.53 and 29.32%) at 48 h in comparison with 24 and 72 h
      (P < 0.05). The number of cells was significantly increased in the GO and G1
      phases and decreased in the S phase after siTRPV transfection (P < 0.01). The
      apoptosis rates of LNCaP cells were 14.45 and 12.73% respectively at 48 h after
      transfected with siTRPV6-1 and siTRPV6-2, significant higher than in the blank
      control and negative control groups (P < 0.05). CONCLUSION: TRPV6-targeted siRNA
      can effectively inhibit the transcription of TRPV6 mRNA, inhibit the
      proliferation of LNCaP cells, arrest their cycles in the G0 and G1 phases, and
      induce their apoptosis.

PMID- 20684324
TI  - [Membrane testosterone receptors in cultured vascular smooth muscle cells].
AB  - OBJECTIVE: To determine the presence of membrane testosterone receptors in
      cultured vascular smooth muscle cells (VSMC), and investigate their relationship
      with classical intracellular androgen receptors (iAR). METHODS: VSMCs were
      cultured from the thoracic aorta of male Sprague-Dawley rats by the explant
      method. Subconfluent VSMCs were incubated with serum-free medium for 24 h to
      obtain quiescent non-dividing cells, and then treated with the indicated agents.
      The aliquots of VSMCs were labeled with testosterone-BSA-FITC (T-BSA-FITC) and
      analyzed by flow cytometry. Classical iARs in intact- and permeabilized-cells
      were detected with anti-iAR antibodies and FITC-labeled secondary antibodies by
      immunofluorescence, followed by flow cytometry analysis. RESULTS: Incubation of
      VSMCs with T-BSA-FITC obviously increased their relative fluorescence intensity
      at 10 sec as compared with the untreated controls (P < 0.01), and so did it at 10
      min in comparison with the treatment with BSA-FITC alone or together with free
      testosterone (P < 0.01). Pretreatment with iAR antagonist flutamide exhibited no
      significant influence on the relative fluorescence intensity of VSMCs (P =
      0.318). Traditional iARs were not detectable on the surface of intact VSMCs,
      although permeabilized cells contained iARs. CONCLUSION: VSMCs contain
      testosterone receptors in the plasma membrane, and these membrane receptors are
      not identical to classical iARs.

PMID- 20684325
TI  - [Expressions of transforming growth factor-beta1, desmin and CD34 in the penile
      corpus cavernosum of rats].
AB  - OBJECTIVE: To detect the expressions of transforming growth factor-beta1 (TGF
      beta1), Desmin and CD34 in the penile corpus cavernosum of SD rats in different
      age groups. METHODS: We randomly selected 10 SD rats in each of the 2-, 5- and 20
      month age groups, harvested their penile corpus cavernosum tissues under ether
      anesthesia, and detected the mRNA and protein expressions of TGF-beta1, Desmin
      and CD34 by RT-PCR and immunohistochemistry. RESULTS: The results of RT-PCR
      showed the mRNA expressions of TGF-beta1, Desmin and CD34 in the corpus
      cavernosum tissues, with significant differences between every two groups (P <
      0.01). The TGF-beta1 protein was mainly expressed in the trabeculae and around
      the arteries of the corpus cavernosum for membrane and cytoplasm staining, the
      Desmin protein mainly in the membrane and cytoplasm for muscle tissue staining;
      and the CD34 protein mainly in the vascular and sinusoidal endothelia. The mRNA
      expression of TGF-beta1 was correlated positively (r = 0.944, P < 0.01) while
      those of Desmin and CD34 negatively with the age of the rats (r = -0.947, P <
      0.01; r = -0.934, P < 0.01). And the mRNA expressions of both Desmin and CD34 had
      a significant correlation with that of TGF-beta1 (r = -0.888, P < 0.01; r = 
      0.887, P < 0.01). CONCLUSION: With the increase of age, the expression of TGF
      beta1 is significantly up-regulated, while those of Desmin and CD34 significantly
      down-regulated in the corpus cavernosum tissues, and it is negatively correlated
      with the latter two. TGF-beta1 is an important influencing factor on ED.

PMID- 20684326
TI  - [Modified serum-guided immunoblotting for differential proteomic study of
      prostate cancer].
AB  - OBJECTIVE: To search for a new method of screening for molecular targets for
      androgen-dependent prostate cancer. METHODS: We collected tissue samples and
      paired serum samples from 3 cases of androgen-dependent prostate cancer (ADPC)
      treated by surgical resection, and included another 3 samples of benign prostatic
      hyperplasia (BPH) tissue and normal human serum in the control group. The total
      proteins extracted were separated and transmembrane by two-dimensional gel
      electrophoresis, followed by hybridization with the sera of the patients with
      ADPC and those with hormone-independent prostate cancer (HIPC) as the primary
      antibodies. The differentially expressed proteins were compared by Western blot,
      analyzed by MALDI-TOF-MS mass spectrography, and verified by RT-PCR and Western
      blot following bioinformatic identification. RESULTS: This modified method
      exhibited a significantly better effect in displaying differentially expressed
      proteins, by which 12 differentially expressed protein spots were identified,
      including Beclin1, glutathione S-transferase P (GSTP1-1), ZBTB7, dihydrodiol
      dehydrogenase 2 (DDH), enolase (ENO1), glucose-dependent insulin-releasing
      peptide receptor (GIPR), Mn-superoxide dismutase (MnSOD), phosphoglycerate mutase
      1 (PGAM1), amino-peptidyl-prolyl cistrons isomerase (PPIA), and phospholipid-PE
      binding protein (PEBP). The mRNA and protein expressions of Beclin1 were
      significantly down-regulated in androgen-dependent prostate cancer tissues.
      CONCLUSION: This modified serum-guided immunoblotting technique has provided a
      new method for clarifying the molecular mechanisms of the occurrence and
      progression of HIPC, in which Beclin1-mediated autophagy may play a key role.

PMID- 20684327
TI  - [Construction of eukaryotic vector of small hairpin interfering RNA against NYD
      SP5].
AB  - OBJECTIVE: NYD-SP5 is a newly cloned gene highly expressed in human testes, which
      consists of 3 598 nucleotides including a 1 027-amino acid open reading frame. It
      is a human-mouse homologous gene. The domain analysis indicated that the NYD-SP5
      protein is a transmembrane protein. This study aimed to design and establish
      recombinant plasmids of small hairpin interfering RNA (shRNA) against NYD-SP5,
      and to pave the way for the analysis of the function of NYD-SP5 in the testis
      using the transgenic mouse model. METHODS: Four sequences of oligonucleotides
      with the small hairpin structure were designed based on the NYD-SP5 mRNA
      sequence. Recombinant plasmids were constructed by cloning these oligonucleotides
      into pGPU6/GFP/Neo vectors. Interfering plasmids against GAPDH were established
      as positive controls and those targeting non-specific genes used as negative
      controls. The positive constructs were verified by enzyme digestion and
      sequencing. RESULTS: Plasmid screening and sequencing showed the sequences of the
      recombinant plasmids to be the same as the shRNA transcribed sequences, which
      indicated the successful establishment of the recombinant vectors. CONCLUSION:
      The shRNA expression vector targeting NYD-SP5 could be established successfully.

PMID- 20684328
TI  - [One-hole high ligation of internal spermatic vein by embryonic natural orifice
      transumbilical laparoscopy: a recommendable treatment of varicocele].
AB  - OBJECTIVE: To evaluate the one-hole method for high ligation of the internal
      spermatic vein by embryonic natural orifice transumbilical laparoscopy. METHODS:
      We used the one-hole method for high ligation of the internal spermatic vein by
      embryonic natural orifice transumbilical laparoscopy in the treatment of 15 cases
      of varicocele, 13 in the left and 2 in the right side, and appraised the
      treatment results by follow-up 1 month after the surgery. RESULTS: All the
      operations succeeded and no complications developed. The average operation time
      was 28 minutes and the mean hospital stay was 4 days. Symptoms were significantly
      relieved in all the patients and the scars were inconspicuous at follow-up.
      CONCLUSION: The one-hole method is a novel option for high ligation of the
      internal spermatic vein by embryonic natural orifice transumbilical laparoscopy
      in the treatment of varicocele. It is recommendable for its advantages of simple
      procedure, less pain, few complications, quick recovery, mini-invasiveness and
      cosmetic acceptability.

PMID- 20684329
TI  - [Diagnosis and management of scrotal Paget's disease: report of 23 cases].
AB  - OBJECTIVE: To explore the clinical manifestation, management, recurrence factors
      and prognosis of scrotal Paget's disease. METHODS: We retrospectively analyzed
      the clinical and pathological data of 23 cases of scrotal Paget's disease
      diagnosed and treated in our hospital from 1996 to 2008. RESULTS: The disease was
      confined to one side of the scrotum in 15, and involved the whole scrotum and
      penis in 8 of the cases. Three patients showed enlarged inguinal lymph nodes in
      the same side, and 2 in both sides. All the cases were confirmed by biopsy and
      treated by surgery. Post-operative follow-up was conducted for 2-68 months, which
      revealed 5 cases of local recurrence and 1 case of death for systemic metastasis.
      CONCLUSION: Biopsy is proved to be important for the early diagnosis of scrotal
      Paget's disease, and extended excision of local lesion is a preferred management.

PMID- 20684330
TI  - [Rediscovery of type III prostatitis related microorganisms].
AB  - Type III prostatitis is a disease that seriously affects men's health. It has a
      high incidence and unclear etiology. The relationship between type III
      prostatitis and certain microorganisms has become better understood with the
      improvement of the techniques for detecting and identifying microorganisms,
      particularly with the wide application of the methods for the analysis of the 16S
      rDNA gene. This review introduces a variety of methods for detecting type III
      prostatitis-related microorganisms, with the purpose of gaining a deeper insight
      into the role of microorganisms in the pathogenesis of type III prostatitis.

PMID- 20684331
TI  - [Sex chromosomes and male infertility].
AB  - Male infertility is a worldwide problem, with a variety of causes including
      genetic factors. Sex chromosomes are particularly interesting, as males only have
      a single copy of both chromosomes. The Y chromosome is obviously an area of
      interest in the study of male-factor infertility because it contains many of the
      genes that are critical for spermatogenesis and the development of male gonads. Y
      chromosome microdeletions are the most commonly known genetic causes of
      spermatogenic failure in males. The azoospermia factor (AZF) region is a
      particular area on the long arm of the Y chromosome, Yq, where microdeletions
      occur most frequently. Fourteen Y chromosome genes encoding putatively functional
      proteins and expressed in the human testis are found to be located in one of the
      three AZF intervals. The exact role of specific AZF genes in spermatogenesis is
      largely unknown, for each of the most classical Yq deletions removes multiple
      genes. The importance of the X chromosome in mammalian spermatogenesis is
      suggested by its enrichment of germ cell-specific genes expressed in
      spermatogenesis, such as AR, USP26, TAF7L, TEX11, KAL1, AKAP4, and NXF2. Genes on
      the X chromosome may be under unique evolutionary pressure due to their
      hemizygous expression in male. The mutations in the single copy X-linked genes,
      unlike in autosomal genes, would not be masked by a normal allele. Many
      researches have been conducted on the relationship between spermatogenesis and
      the genes on the X chromosome, but the involvement of the X chromosome in male
      infertility remains less understood and deserves further characterization.

PMID- 20684332
TI  - [Chinese medicinal monomer and compound for 60Co-gamma-induced spermatogenic
      disturbance in mice].
AB  - OBJECTIVE: To explore the effects of the monomer and compound of the Chinese
      herbal drugs resveratrol, lycium barbarum polysaccharide (LBP) and icariin on
      60Co-gamma-induced spermatogenic disturbance in mice based on the theory of
      modern Chinese medicine. METHODS: A total of 105 male Kunming mice were randomly
      divided into seven groups, with 15 in each. Group A were normally raised and
      Groups B, C, D, E, F and G irradiated by 60Co-gamma 6 Gy followed by 60Co-gamma 4
      Gy at the interval of 7 days. A week later, Groups C, D, E, F and G received
      intragastrically the suspension of resveratrol, resveratrol + LBP, resveratrol +
      icariin, resveratrol + LBP + icariin and resveratrol + LBP + icariin + L
      carnitine, respectively, at the dose of 80 mg/(kg x d) for 60 days. The general
      condition, physical signs and body weight changes of the mice were recorded, and
      24 hours after the intragastric medication, their testes were harvested to obtain
      the testicular weight and indexes, the levels of FSH, LH, T and E2 determined by
      ELISA, the T/E2 ratio calculated, and the histology of the testis tissues
      observed under the microscope. RESULTS: The testicular indexes of the mice were
      decreased by radiation-induced damage, but restored to some extent after
      intragastric medication, especially in Groups E, F and G. The levels of FSH, LH
      and T were obviously improved by LBP. The T level and testis weight were
      increased by Icariin. The level of T/E2 was elevated in Groups E, F and G. The
      best results were achieved in Group F, which exhibited almost complete recovery
      from reproductive endocrine disorder and spermatogenic damage. CONCLUSION: The
      Chinese medicinal monomer is effective for 60Co-gamma-induced spermatogenic
      disturbance in mice, and the compound suspension of resveratrol + LBP + icariin
      produces the best result.

PMID- 20684333
TI  - [Multiple myeloma--analysis of patients diagnosed in Internal Diseases and
      Nephrology Department and Dialysis Center St. Lukas Hospital in Tarnow in years
      1999-2009].
AB  - We analyzed 25 patients with multiple myeloma. All the patients fullfilled
      diagnostic criteria of International Myeloma Working Group (2003): presence of
      monoclonical protein in serum or/ and in urine (IgG 64%), IgA -16%, free light
      chains - 16%, in one patient (4%) biclonal typ plasmocytoma was diagnosed), at
      least 10% plasmocytes in the bone marrow and at list one evidence of end-organ
      damage such as anemia (92%), bone lesions (65%), hypercalcemia (36%) and renal
      insufficiency (92%). Acute renal failure was diagnosed in 60% of patients and 32%
      with chronic renal failure. Only 2 patients had normal renal function. 36% of
      patients required hemodialysis. Our analysis showed that almost all patients were
      admitted to hospital at a very advanced stage of the disease and renal failure
      was dominant, mostly at advanced stadium.

PMID- 20684334
TI  - [Measurement of the passive compliance of the total respiratory system in newborn
      after respiratory insufficiency for risk assessment of respiratory disorders
      during the first 6 month of life].
AB  - AIMS: To evaluate the relationships between postnatal passive respiratory
      compliance (Crs) and development of respiratory disorders during the first 6
      month of life in preterm and full-term infants after respiratory insufficiency.
      The purpose of this study was to investigate whether other relevant neonatal
      factors, like degree of prematurity, birth weigh, ventilatory conditions, sepsis,
      and respiratory disease severity affected this relationship. MATERIAL AND
      METHODS: The passive respiratory compliance was measured by the single occlusion
      technique in 73 preterm infants after respiratory distress syndrome (RDS), 19
      full-term infants after congenital pneumonia and 33 healthy full-term infants.
      Respiratory function measurements were performed by single occlusion technique,
      during natural sleep, after acute phase of illness, before discharge from
      neonatal department. RESULTS: Crs was significantly lower in premature newborns <
      36 weeks gestation after RDS (p = 0.0002) and in term newborns who have suffered
      from a congenital pneumonia (p = 0.0411), than in healthy full-term newborn
      infants. Premature infants who have undergone sepsis have significantly decreased
      Crs in relationship with those who did not have this complication (p = 0.0334).
      Preterm newborns who have suffered pneumonia during treatment of RDS have
      significantly frequent respiratory problems during the first 6 month of age (p =
      0.043). Full-term infants after congenital pneumonia have more but not
      significantly frequent respiratory problems than healthy term newborns (p =
      0.055) in this period. Decreased neonatal Crs wasn't significantly related to
      respiratory disorders in age of 6 month of life. CONCLUSION: Prematurity under 36
      week of gestational age, low birth weight and suffering from sepsis in premature
      infants significantly decreased Crs in newborn. Decreased neonatal Crs in
      premature and full term infants after respiratory insufficiency wasn't
      significantly related to respiratory disorders during first 6 month of life. This
      study has showed significantly increase of respiratory problems in this period in
      preterm infants who have suffered from pneumonia during neonatal period.

PMID- 20684335
TI  - [Identification of Staphylococcus aureus in homogenates of hypertrophic adenoid
      (a preliminary report)].
AB  - Standard adenoid swabs were taken from 33 children subjected to adenotomy. The
      bacterial growth was determined in swabs samples and in homogenates of surgically
      removed lymphatic tissue. Homogenates were also used for isolation of bacterial
      DNA. A standard bacteriological examination revealed the presence of
      Staphylococcus aureus only in 11 children (33%). In stark contrast S. aureus was
      detected in 20 samples (60%) of homogenized tissue, including all 11 positive
      swabs specimens. Results of plating were confirmed by molecular test (PCR-
      polymerase chain reaction). Inconsistent results between swabs and homogenate
      plating may indicate intracellular localization of S. aureus the tissue of
      hypertrophic adenoids.

PMID- 20684336
TI  - [The presence of apoptotic neutrophils in contents of neck lateral cysts].
AB  - During the 2001-2003 time period 17 patients with neck lateral cysts were
      subjected to surgery at the Department of Otolaryngology, Regional Hospital in
      Tarnow. Collected cysts contents were analyzed with respect to bacterial
      infection and neutrophil presence as a measure of ongoing local inflammation. All
      samples were shown being sterile and half of them contained large numbers of
      neutrophils in advanced apoptosis. The apparent lack of efficient clearance of
      apoptotic neutrophils may lead to maintenance of the local inflammatory reaction
      in the neck cysts.

PMID- 20684337
TI  - [The influence of cryochamber on parameters of blood pressure and pulse].
AB  - INTRODUCTION: The influence of whole body cryotherapy on human body. MATERIAL AND
      METHODS: The study was conducted on a group of 50 patients of the Rehabilitation
      Ward in Wojewodzki Szpital Zespolony in Kielce suffering from chronic pain as a
      sequel of degenerative-deformative changes and residing. Physiotherapy consisted
      of treatments in cryo-chamber and physical exercises. RESULTS: The average heart
      rate in the study group before the treatment amounted to 66.5 beats/min +/- 5.7
      after the courses of treatments it constituted to 63.1 beats/min. +/- 3.6 at the
      significance level p < 0.001. The average value of systolic blood pressure in the
      study group before treatments accounted for 118.7 mmHg +/- 10.8 after the course
      of treatments amounted to 119.9 mmHg +/- 11.6 at the significance level p <
      0.001. CONCLUSION: The single treatment of the whole body cryotherapy and 10
      courses of those combined with physical exercises caused statistically
      significant reduction in the heart rate and pressure parameters. The downward
      trend was observed in all courses of treatments conducted in this study.

PMID- 20684338
TI  - [The treatment of infection after primary total knee arthroplasty with a focus on
      the usefulness of Spacer-K].
AB  - Management of infectious complications after primary total knee arthroplasty with
      a particular focus on the clinical usefulness of Spacer-K is presented in the
      following article. The choice of treatment depends on the timing of infection
      onset. The gold standard in the treatment of late infections is a two-stage
      exchange arthroplasty with usage of temporary antibiotic-loaded spacer
      prosthesis. The role of diagnostics and prompt treatment is emphasized. Applied
      management as well as treatment results have been analyzed.

PMID- 20684339
TI  - [Problems with treatment of trochanteric femur fractures at elderly patients].
AB  - Authors analyzed patients complications with trochanteric fractures of femur
      treated in Department Orthopedic and Casualty of St. Lukas Hospital in Tarnow
      from 01.01.2008 to 31.12.2009 in this study. During this period were treated 167
      patients. In most of cases operative treatment such as: Dynamic Hip Screw
      fixation, Gamma nailing, Ender's method and angle plate with screws were used.
      Prosthetic replacement was also used and 9 patients weren't operated because of
      coexisting pathological states. Basing on a done analyze of clinical material it
      was pronounced that independently from used surgical procedure regional and
      general complications are being occurred.

PMID- 20684340
TI  - [Assessment of the results of rehabilitation treatment after osteosynthesis of
      femoral trochanter fractures with Gamma nails].
AB  - The work presents the results of the rehabilitation after osteosynthesis of
      femoral trochanter fractures with the Gamma nails. Femoral trochanter fractures
      usually affect the elderly and senile patients, which require the use of
      appropriate methods of operation as well as intense rehabilitation. Early and
      intense post-operational management, based on physiotherapy has advantageous
      effects on the process of mobilization of the patients. In the majority of them
      it allows to regain the pre-traumatic ability, mobility and activity.

PMID- 20684341
TI  - [Outcomes of surgical treatment of proximal humerus fractures in elderly people].
AB  - The aim of the study is analysis of outcomes of surgical treatment in a group of
      32 patients with fractures of the proximal humerus treated surgically in the
      orthopaedic and traumatic ward of St. Lucas Hospital in Tarnow during the years
      2006-2009. Results were estimated by Constant-Murley criteria. Among the surgical
      methods the best results were observed in cases of healing with percutaneus
      Kirschners wires fixed appropriately with the closed method of two- and three
      part fractures of the neck of the humerus. The worst results were observed in
      four-part humerus fractures when open surgical procedure were used irrespective
      of the kind of applied implant. In case of these fractures of proximal humerus,
      satisfactory results were obtained by using hemi-arthroplasty.

PMID- 20684342
TI  - [Results of intramedullary fixation in the treatment of multiple fractures of the
      long bones].
AB  - Results of treatment of multiple long-bone fractures are presented in the
      following article. 13 patients treated with intramedullary fixation were included
      into our study. Obtained results confirm that intramedullary osteosynthesis is a
      good method to be recommended.

PMID- 20684343
TI  - [The surgical treatment outcomes of acromio-clavicular joint dislocation healing
      with closed reposition and Kirschners' wires stabilisation].
AB  - The results of surgical treatment of acromioclavicular joint dislocation in 21
      patients using closed reposition and stabilization with the use of 2 Kirschner
      arrowheads were presented in this study. Results of treatment were obtained on
      the basis of movable shoulder joint restriction, severity of pain, radiological
      images, as well as a subjective assessment of the operated limb function.
      Observation period ranged from 3 months to 3 years. It has been concluded, that
      closed reduction and fixation with Kirschner wires (arrowheads) is simple, barely
      invasive method of treatment for acromioclavicular dislocation and gives good
      final results, although a significant percentage of complications was observed.

PMID- 20684344
TI  - [Nurse care standard of sick people after endoarthoplasty of hip].
AB  - INTRODUCTION: The clinic's practice prove that successfully done endoarthoplasty
      depends not only on the right execution and good chose of endoprosthesis but also
      depends on good nurse's care before and after operation. The aim of that work is
      to show the modern model of nursering based on nursing's standard. MATERIALS:
      Series of trainings for nurse staff after endoarthoplasty of hip joint were taken
      on orthopedic trauma surgery unit in hospital in Tarnow. The aim of trainings was
      to speak about standard of nursering after endoarthoplasty of hip joint. Standard
      includes two periods: period before operation, period after operation. In second
      part the standard of nursering and its practical use is showed. DISCUSSION: Good
      operation results, confirmed by satisfaction of patients after operations, show
      that a team, which takes care of ill people, works on modern model of nursering.
      CONCLUSIONS: The nurses, who were trained on the orthopedics and injury sections
      on orthopedic trauma surgery unit in hospital in Tarnow from rules of
      applications the standards of nursering after endoarthoplasty of hip joint in
      higher range make planning nursering interventions. The increase of knowledge and
      sensitize medical staff on patient's needs may have fundamental influence on
      quality of provided services.

PMID- 20684345
TI  - [The nursing standards and streamlining sick persons after hip replacement].
AB  - INTRODUCTION: The aim is to show the modern model of streamlining based on
      nursing's standard. MATERIALS: The rules of streamlining sick after hip
      replacement. During patient's staying in hospital, in every contact with sick we
      try to mark his psychical and psychological state. In judgment of psychical state
      we try to tell what is the attitude of the patient to himself, to the illness, to
      treatment, other patients and to medical staff. Information can help in planning
      an effective therapy for this patient. 2. Preparing the patient to returning
      home. Before living the hospital it is very important to prepare a patient to
      live with artificial hip. To continue the therapy program (exercises) patient
      should feel responsibility for success of rehabilitation. Intensive exercises are
      necessary according to recommendations of therapist. DISCUSSION: Leading the
      nursery standards on orthopedic trauma surgery unit in hospital in Tarnow pay
      attention to medical staff on problem connected with wide understanding
      improvement of patient after hip reconstruction. CONCLUSIONS: The increase of
      knowledge and make the medical staff more sensitive on patient's needs may have
      fundamental influence on quality of provided services.

PMID- 20684346
TI  - [Parenthood in aspect of multiple sclerosis].
AB  - Multiple sclerosis is a central nervous system disease. It is mainly
      characterized by passing neurological disorders at first which alter into
      permanent symptoms. The most frequent are tiredness, sensation disturbance and
      limbs, face, body becoming numb. Pregnancy doubtfully influence MS, but the most
      important question is about treatment during pregnancy. Should we carry pregnancy
      during immunomodular treatment? But crucial aspect is if a newborn baby will be
      healthy. To make attempt into discussion about the subject of SM and pregnancy we
      should perform a test how many sick people get married and or if maternity and
      paternity influence a disease course. Our research may bring answers, why
      statistically less SM men become single and do not own children and if unmarried
      status is influenced by sexual disturbance. Our conclusion will be compared with
      already written facts. Patients were between 18-35 year old are the subject of
      research. The group consist of 24 patients, 9 men and 15 women. Final conclusion
      could bring the answer if definite willingness to have a baby should be
      recommended.

PMID- 20684347
TI  - [Quack medicine--a continual problem in Polish rural communities. Illnes
      occurring within the musculo-sceletal system].
AB  - The work presents the results of a survey that was conducted amongst the
      inhabitants of the parish of Dabrowa Tarnowska concerning quack medical practices
      noted in the treatment of the musculo-sceletal system, as well as comments on the
      subject of the harm caused by the application of folk remedies. Within the group
      of those surveyed a startling 79% evaluated this form of treatment as
      satisfactory despite the appearance later of many medical complications.

PMID- 20684348
TI  - [Poison cases and types of poisons based on data obtained of patients
      hospitalized from 1995-2009 with acute poisoning in the second internal ward in a
      multi-profile provincial hospital in Tarnow].
AB  - The thesis presents a short history and organization of an acute poisoning centre
      in the1995 functioning within the internal diseases department in a multi-profile
      provincial hospital. The data show the number of patients treated beetween 1995
      2009 an the types of toxic substances that caused poisoning. The conclusions
      presented refer to the role of the centre to help people suffering from acute
      poisoning within the city of Tarnow.

PMID- 20684349
TI  - [The assessment of bone status in women with rheumatoid arthritis].
AB  - The aim of the study was to evaluate the skeletal status by means of several
      technics (bone densitometry, radiography, ultrasound) in females with rheumatoid
      arthritis in comparison with healthy controls. Therefore, the evaluation of the
      progress of osteoporosis and the assessment of clinical utility of various
      methods were possible. Dual X-ray absorptiometry measurements were performed at
      following skeletal sites: spine, proximal femur, forearm. Quantitative ultrasound
      measurements included calcaneus and hand phalanges, and radiography allowed for
      calculation of metacarpal index. Laboratory Variables include indictors of
      activity of disease. The progress of the disease was assessed by Steinbrocker
      stages, all patients completed a health assessment questionnaire (HAQ), and
      activity of the disease was assessed by DAS 28. In the study 104 women we
      evaluated (62 with rheumatoid arthritis as defined by ACR and 42 healthy controls
      in mean of 54.2 +/- 5.1). The mean age in patients was 56.5 +/- 9.9 years, and
      the mean disease duration 167.8 +/- 126.1 months. 21 (34%) were in II stage of
      the disease according to Steinbrocker stages. All measured skeletal variables
      were significantly lower in patients than in controls (p < 0.0001). The results
      of the study indicate that in women with rheumatoid arthritis bone status is
      seriously affected. All used methods allowed for comparable diagnosis of bone
      deterioration. A high ratio of subjects with low bone density indicates that
      patients with rheumatoid arthritis ought o be routinely evaluated towards
      osteoporosis followed by antiresorptive therapy.

PMID- 20684350
TI  - [Influence of nutrition and eatables on human being health].
AB  - Over 60 diseases, civilization cardiovascular system diseases (hypertension,
      myocardial infarction, ischaemia legs, stroke, especially), metabolic diseases
      (metabolic syndrome, type 2 diabetes mellitus, osteoporosis), and cancers
      (gastric carcinoma, prostatic carcinoma, colonic carcinoma, breast carcinoma in
      women) are as a result of the defective nutrition. Even though human genome did
      not change essential but a diet and a lifestyle of contemporary human being
      radical differs from prototype of our ancestors. One take notice of world
      epidemic of over weight and obesity. Contemporary diet should realize following
      aims: a/prevents diseases, b/ does not create health risk and c/ supplies with
      good taste and in this way secures the most of quality life. Author discusses
      sources and causes the contamination of food by free radicals, heavy metals,
      glucotoxins and other chemical compounds. Next, presents the newest model of the
      food pyramid and the role of polyunsaturated fatty acids in the prevention of
      civilization diseases. Special attention paid on the health profits as a result
      consumption of minimal processed food and marine fishes.

PMID- 20684351
TI  - [Osteoporosis in orthopedics--disease of civilization].
AB  - Osteoporosis is classificatied by WHO as one of the main civilizations diseases
      and is situated on the third place as a cause of death. Epidemiological data
      indicates that 25% of Polish population after 50 years old risk osteoporotic
      fractures. Low BMD, which coexist in osteoporosis is the main reason of the
      osteoporotic fractures. Orthopaedic procedures of osteoporosis and it's main
      complications--fractures are symptomatic. Orthopaedy tends for new implants
      technology and modern surgery procedure left the nonoperative treatment as for as
      possible.

PMID- 20684352
TI  - [Physiotherapeutic management of patients after surgical treatment of nucleus
      pulposus prolapse in the lumbar section of the spine].
AB  - The conservative treatment of patients with low back pain syndrome frequently
      provides an insufficient form of patients' mobilization, which therefore requires
      more invasive and more complex treatment techniques. Surgical treatment, which is
      the ultimate form of medical interference, is supported by rehabilitation
      techniques ensuring advantageous and relatively prompt effect.

PMID- 20684353
TI  - [Ochronosis as a cause of multiple joint osteoarthritis in one patient].
AB  - The paper presents a 62-year-old patient with ochronotic polyarthropathy.
      Bilateral total knee arthroplasty, as well as shoulder joint alloplasty was
      performed. The patient is still remaining under observation and treatment because
      of degenerative lesions of the vertebral column and both hip joints.
      Pathogenesis, clinical and histopathological presentation, as well as the
      possibilities of diagnostics and treatment of the disease are discussed.

PMID- 20684354
TI  - [Total hip arthroplasty as solution to the problem of trochanteric fracture of
      the femur in patient with severe hip osteoarthritis].
AB  - The paper presents a case of sub- and intertrochanteric fracture of the right
      femur in a patient with coexisting severe osteoarthritis of the ipsilateral hip.
      The patient underwent silmultaneous fracture treatment and total hip replacement.
      Applied management as well as treatment results have been analyzed.

PMID- 20684355
TI  - [Dislocation of hip resurfacing endoprosthesis--a case report].
AB  - A case of dislocation of hip resurfacing prosthesis is reported. The patient is
      described because of extreme rarity of such a complication among patients treated
      with hip resurfacing arthroplasty.

PMID- 20684356
TI  - [Datura intoxication--report of three cases].
AB  - In recent months, more and more reports have appeared about datura seed
      poisoning. Datura is widespread and has hallucinogenic properties. It is part of
      the increase in drug use among the younger generation that is experimenting with
      intoxicants. The hallucinogenic and poisonous effects of datura involve the
      presence of tropine alkaloids: atropine and scopolamine. They both have similar
      effects, suppressing the parasympathetic peripheral nervous system. In large
      doses they lead to death as a result of respiratory paralysis. Treatment
      addresses the symptoms. In order to eliminate toxic effects of atropine, an
      antagonistic medication such as neostigmine is given.

PMID- 20684357
TI  - [49 year old patient with staphylococcal sepsis caused by agranulocytosis after
      polychemotheraphy].
AB  - This study presents a case of adverse effects of chemotherapeutic agents:
      alkylating drug (cisplatyna) and taksoin (taxol) on a patient with metastatic
      cancer of unknown primary which was manifesting with Krukenberg tumor symptoms.
      The main disease symptoms were caused by bone marrow malignant infiltrations, and
      pancytopenia in peripheral blood, but mainly staphylococcal sepsis and
      hemorrhagic diathesis. In conclusion, the need to be cautious while making the
      decision to implement chemotherapy on patients with very advanced cancer in terms
      of prolonging their lives was pointed out.

PMID- 20684358
TI  - [Extensive olfactory neuroblastoma of the nasal cavity and paranasal sinuses].
AB  - The authors describe a clinical case of extensive olfactory neuroblastoma,
      comprehensive the nasal cavity, paranasal sinuses and orbit who was treated in
      Otolaryngology Department of the Regional Hospital in Tarnow. The patient was
      treated with surgery and radiotherapy without orbit exenteration and the 2--year
      local progression--free survival was observed. Staging system, diagnostics and
      therapeutic methods were analyzed. Diagnostic difficulties in olfactory
      neuroblastoma recognition and value of the immunohistochemical examinations were
      emphasized.

PMID- 20684359
TI  - [Side effects of temozolomide treatment in patient with glioblastoma multiforme-
      case study].
AB  - In case study, we presented patient with glioblastoma multiforme-brain tumor
      grade IV-WHO. Patient after surgery, followed by radiotherapy and chemotherapy,
      after cycles of chemotherapy with temozolomid. During therapy with temozolomid,
      it is recommended to check morphology on the 22nd day of cycle. Patient did not
      come for follow-up appointment, also she did not do any of follow-up tests. She
      came to the hospital 2 weeks later, in poor general condition with peripheral
      pancytopenia, neurological disorders and shortness of breath.

PMID- 20684360
TI  - Biological breakdown.

PMID- 20684361
TI  - Tools for life.

PMID- 20684363
TI  - An extra quiet sun.

PMID- 20684362
TI  - Danger in school labs.

PMID- 20684364
TI  - Hereditary acquisitions.

PMID- 20684365
TI  - Worts and all.

PMID- 20684366
TI  - Charge under control.

PMID- 20684367
TI  - Catastrophic thinking.

PMID- 20684368
TI  - Market reforms, 20 years later.

PMID- 20684369
TI  - Our neandertal brethren.

PMID- 20684370
TI  - Faith and foolishness.

PMID- 20684372
TI  - Origins.

PMID- 20684371
TI  - Planets we could call home.

PMID- 20684373
TI  - When the sea saved humanity.

PMID- 20684374
TI  - Robot pills.

PMID- 20684375
TI  - Threatening ocean life from the inside out.

PMID- 20684376
TI  - Filming the invisible in 4-D.

PMID- 20684377
TI  - The hacker in your hardware.

PMID- 20684378
TI  - Plastic surf.

PMID- 20684379
TI  - [Optimalization of biocompatible artificial tears containing povidone-iodine
      according to pharmaceutical technological and microbiological aspects].
AB  - Microbiological preservatives play a great role in the preparation of artificial
      tears because they protect the eyes from further microorganisms and the
      preparation from contamination. In this contribution we are summarizing our
      experimental results given by pharmaceutical and microbiological optimalization
      of artificial tears. The incidental adaptability of povidone-iodine (PVP-I) as a
      preservative in artificial tears was examined compared to usually used materials.
      Some artificial tears (Oculogutta carbomerae and Oculogutta viscosa) were
      prepared according to the Formulae Normales Edition VII., others were
      isotonisated and buffered containing 3.0% and 3.5% povidonum as active substance.
      The analysed samples as a preservative instead of generally used agents contained
      0.10%, 0.05% and 0.01% PVP-I. Reference preparations were dispensed using
      microbiological preservatives (Cetrimidum, Thiomersalum solutum 0.1%,
      Benzalconium chloratum solutum 10%). Pharmaceutical (pH, viscosity, freezing
      point depression, refraction, surface-tension) and microbiological (breeding on
      aerobe and anaerobe bacteriological culture medium) trials were made to determine
      the qualitative property and adaptability of analysed preparations in which we
      also studied the stability and the microbiological changes after opening them.
      According to our experimental results we can establish that the PVP-I is suitable
      as microbiological preservative in the examined preparations.

PMID- 20684380
TI  - [Analysis of direct costs during the treatment of tuberculosis in childhood].
AB  - Incidence and prevalence of tuberculosis (TB) shows a decreasing tendency in
      Hungary. The medical care of these patients represents a substantial cost to the
      health services. We assessed the direct costs of paediatric patients with TB in a
      Hungarian hospital. Patients participating in the study were 9 children, with an
      average age of 11.17 +/- 6.34 years. In the study group there were two immigrant
      patients (22, 23%), two (22, 23%) had multidrug-resistant TB (MDR-TB), five
      patients (62.5%) were contacts, six (66, 67%) had extrapulmonary tuberculosis and
      three (33, 34% suffered from other co-morbidities. The average direct cost of
      pulmonary TB was 2920 Euros, direct cost of MDR-TB was between 7300-9120 Euros.
      MDR-TB increases one and half times the period spent in hospital, two and half
      times the cost of inpatient care. Extrapulmonary TB with concomitant disease
      causes 3-7 times higher expenditures to the health service. According to our
      results we found significant differences between the cost of actual therapy and
      resources available; thus the compensation needs to be solved.

PMID- 20684381
TI  - [Pharmacoeconomic impact of compliance].
AB  - Medication compliance has important consequences for clinical outcome and for
      health care costs. From the perspective of the pharmaceutical industry and the
      health-care provider it is necessary to incorporate non-compliance into
      pharmacoeconomics evaluations. The aim of the review was to give an overview of
      the pharmacoeconomics importance of medication compliance. The impact of non
      compliance on health care costs and quality of life, as well as the cost
      effectiveness of compliance and compliance enhancing interventions were
      evaluated. In summary, there is a clear need for more research on the field of
      non-compliance to find out more about the pharmacoeconomic impact of medication
      taking behaviour.

PMID- 20684382
TI  - [The role of pharmacists, members of the Hungarian Academy of Sciences, in the
      history of chemistry].
AB  - In this study we present the role of Hungarian academic pharmacists in the
      history of chemistry and in university education since the formation of the first
      chemistry department until today. After a short resume we summarize the teaching
      activity and main research fields of each scholar. Pictures, chemical formulas,
      interesting and personal moments based on recollections of students and
      colleagues make the discussion more colorful.

PMID- 20684386
TI  - [Art in the hospital].

PMID- 20684387
TI  - [Art and medicine, history of an encounter].
AB  - Art has always been linked to healthcare and medicine: at the beginning of time,
      art was considered to be therapeutic. Over time, the dominance of religion and
      then the development of sciences and medicine deprived art of its therapeutic
      role, before it was reintroduced in the 19th century, with the rapid development
      of psychiatry. Today, art has found a new place in healthcare.

PMID- 20684388
TI  - [Cultural expressions in maternity. Interview by Catherine Strumeyer].

PMID- 20684389
TI  - [Music in the hospital].
AB  - Occasional events, regular workshops, concerts, shows, artists in residence,
      cultural outings...Hospital does not necessarily have to be a place of silence
      and sadness. But this situation has not always been so straightforward as on the
      face of it, nothing is more incompatible with a hospital environment than music,
      which, by definition, is festive and noisy.

PMID- 20684390
TI  - [Associating children with contemporary visual arts in the hospital].
AB  - In 2008, for 3 months, a visual artist in residence at the Margency children's
      hospital (Val d'Oise) made sculptures for the bandstand situated in the
      hospital's park. By bringing people together this experience helped to create a
      bond between the artists, the hospitalised children and the healthcare workers.

PMID- 20684391
TI  - [Photography, language and healthcare].
AB  - Photography as an art is a way of accessing our emotions, naming them,
      understanding them and taking them into account in the healthcare relationship. A
      training session on the Photolangage method enables us not only to increase our
      knowledge but also to share our emotional experience and encourages reflection.

PMID- 20684392
TI  - [Art in the hospital].

PMID- 20684393
TI  - [A unit dedicated to minor victims of violence].
AB  - Law 98-468 of 17th June 1998 enables hearings for minor victims of aggression or
      sexual assault to be filmed. This legal procedure can sometimes be traumatic. In
      the region of Picardie, units dedicated to underage victims have been developed.
      These units bring together all the relevant professionals in a reassuring
      environment suitable for children, in order to encourage the child to talk and to
      help make the whole procedure easier.

PMID- 20684394
TI  - [The adaptation of fathers to their first newborn].
AB  - With the arrival of their first child, fathers see their identity overturned.
      Their adjustment to their first baby must be taken into account by their family
      and friends and perinatal heathcare professionals. A review of the literature on
      this subject enables us to identify and define the different adjustment phases of
      today's fathers, as well as the factors favouring their commitment to their new
      role.

PMID- 20684395
TI  - [11/12. Meningitis in children].

PMID- 20684396
TI  - [4/6. Embryo transfer].

PMID- 20684397
TI  - [Heads in the air].

PMID- 20684398
TI  - [Targeting inertia and therapy non-compliance: new challenge for improving
      medical practice performance].

PMID- 20684399
TI  - [Inertia in clinical practice: causes, consequences, solutions].
AB  - Therapeutic inertia is one of the components of clinical inertia. It mainly
      concerns the management of chronic diseases. It may be defined as the attitude of
      health care providers who do not initiate or intensify therapy appropriately
      despite recognition of the problem. Multiple causes may be identified, related to
      the physician but also to the patient and to the health care system. The
      consequences may be dramatic, both for the patient, in terms of quality of life
      and/or life expectancy, and for the society, because of the huge cost resulting
      from complications due to therapeutic inertia. Thus, various solutions should be
      proposed to help solving this important public health problem, focusing the
      actions on the physician, the patient and/or the health care system.

PMID- 20684400
TI  - [Non compliance to medical therapy; causes, consequences, solutions].
AB  - Compliance is defined as the extent to which a patient's behaviour coincides with
      medical or health advice. Medication adherence seems to be rather low as 30 to
      60% of patients with chronic disease may be categorised as being poorly or not
      adherent to drug therapy. Numerous factors may influence compliance among which
      patient's characteristics, disease peculiarities, drug treatment modalities,
      physician's attitudes and health system organisation. The consequences of non
      compliance to drug therapy may not only be harmful for patient's health, but
      could also negatively impact the financial cost of public health services. Thus,
      all efforts should be focused to improve drug compliance, if possible by
      targeting all causes responsible for poor adherence to medications.

PMID- 20684401
TI  - [Strategies avoiding inertia and non compliance in clinical trials].
AB  - Randomised controlled trials play a key role in evidence-based medicine as far as
      the assessment of both efficacy and safety of drugs is concerned. Various
      strategies are used to avoid physician's inertia and to combat patient's non
      compliance, two pitfalls that may hinder the demonstration of the therapeutic
      efficacy of the drug. Clinical inertia may be limited by titration, forced or
      optional, driven by therapeutic targets, or by the use, if necessary, of rescue
      medications. Compliance may be verified by "pill count". This simple technique
      allows to exclude non compliant patients when they are detected during the
      placebo run-in period before randomisation or not to take into account patients
      with poor compliance in the final evaluation by using a statistical analysis
      restricted to individuals who have strictly adhered to the study protocol ("per
      protocol analysis"). Self-monitoring and patient's empowerment in the treatment
      also contribute to improve drug compliance. Clinicians may take advantage of
      these approaches derived from clinical trials to improve their daily practice.

PMID- 20684402
TI  - [Therapeutic education: a solution to reduce therapeutic inertia and
      noncompliance].
AB  - Therapeutic education (TPE) aims to enable the patient suffering from a chronic
      diseases to manage his/ her illness and treatment, and prevent avoidable
      complications, while keeping or improving his/her quality of life. It comprises a
      set de practical tools aiming the patient to acquire skills to manage
      himself/herself the disease, its care and supervision, in partnership with
      healthcare providers. TPE may contribute to improve therapeutic compliance and to
      reduce clinical inertia, two drawbacks frequently encountered in the management
      of patients with chronic diseases. As an illustration, we briefly present EDUDORA
      ("Education therapeutique et preventive face au diabete et a l'obesite a risque
      chez l'adulte et l'adolescent" = "Preventive and therapeutic education for
      diabetes and at risk obesity in adults and adolescents"), an ongoing original
      project in three frontier regions (Wallonia - Grand-Duchy of Luxembourg -
      Lorraine).

PMID- 20684403
TI  - [Clinical inertia in geriatrics].
AB  - Therapeutic inertia is a phenomenon with multiple etiologies, characterized by a
      "lack of initiation or modification of therapy when appropriate" and mainly
      affecting common chronic diseases (hypertension, diabetes, dyslipidemia). Caused
      by various processes including the lack of clinical evidence for the elderly, it
      can lead, in the elderly fragile by nature, to inappropriate prescribing. In a
      multidisciplinary approach, integrating the expertise of a pharmacist in the
      health care team improves the pharmacotherapeutic management of the geriatric
      patient.

PMID- 20684404
TI  - [Therapeutic adherence in elderly].
AB  - Therapeutic adherence can be defined as the degree of concordance between the
      behaviour of a person in relation with drugs prescription and medical
      recommendations. It represents the ability of people to follow a treatment. Bad
      adherence is frequent in geriatric patients. The behaviour of the patient is
      important but the role of the prescriptor and distributor of the drugs should
      also be emphasized. A bad adherence is responsible for iatrogenic consequences,
      which has a great impact on the functionality of the old person, but also on the
      cost and organization of care. Therapeutic education, a standardised method to
      help the patient take care of his own treatment, must be developed. The aims and
      means should be clearly efined. The patient himself must be involved and human or
      material sources of help must be sought.

PMID- 20684405
TI  - [Cardiovascular prevention: could the polypill reduce the risk of clinical
      inertia and poor compliance?].
AB  - The concept of "polypill" for cardiovascular prevention was introduced in 2003 in
      a landmark paper of the British Medical Journal. A model based on results
      provided by evidence-based medicine suggested that a "polypill", that contains a
      statin, three blood pressure lowering drugs (each at half standard dose), aspirin
      and folic acid, would result in an 80% reduction in the incidence of coronary and
      cerebrovascular events, while being associated with a good tolerance profile and
      offering a favourable cost-effectiveness ratio. The present paper aims at
      presenting the new advances dealing with this new paradigm in cardiovascular
      prevention. We will present the progresses of the "polypill" concept since 2003,
      the results of a first controlled clinical trial, the pharmaceutical feasibility
      for routine clinical use and the potential pharmaco-economical impacts of such a
      strategy. The "polypill" may offer a solution to avoid physician's clinical
      inertia and reduce patients's lack of compliance, two drawbacks in the field of
      cardiovascular prevention.

PMID- 20684406
TI  - [Therapeutic inertia in hypertension: why and how to fight against this
      attitude?].
AB  - Therapeutic inertia, i.e. the absence of introduction of an antihypertensive
      treatment or on adjustment of its intensity by the medical doctor if the blood
      pressure is elevated or the goal not reached, is frequent and does play a role in
      the insufficient control of blood presure in the hypertensive population. The
      responsibility of the medical doctor is high in this respect. A strict medical
      approach is required, step by step, to correct this lack of reaction.

PMID- 20684407
TI  - [Importance of a bad adherence to the antihypertensive treatment in the
      hypertensive population. How to improve it?].
AB  - Overwhelming evidence indicates that the treatment of arterial hypertension is
      beneficial, but, in practice, less than 50% of treated hypertensive patients have
      well-controlled blood pressure. The success of treatment relies upon adherence
      (for both non pharmacologic and drug treatment) by the patient. This problem of
      observance is multifactorial. Several factors play a role: the patient, his/her
      illness, his/her treatment and the therapeutic environment where the relationship
      between the medical doctor and the patient is crucial. To improve observance, but
      also treatment persistence we need to think about it. Observance must be
      discussed with the patient at each visit. An excellent relationship between
      doctor and patient, education about hypertension, its risks, and the ways to
      avoid complications, the choice of a well tolerated and simple treatment
      progressively introduced, the intervention in this management of the family and
      the pharmacist, the development of home self blood pressure measurement by the
      patient are all important ways to improve adherence. This could reduce the
      cardiovascular complications related to high blood pressure and thus decrease the
      general costs for the society.

PMID- 20684408
TI  - [Treatment adherence to guidelines for the management of chronic heart failure].
AB  - Chronic heart failure is a growing public health problem with a bad prognosis.
      Despite the seriousness of this syndrome and the well defined therapeutic
      approach, adherence to guidelines remains poor. After briefly recalling the main
      points of these guidelines, we present statistical data regarding therapeutic
      care of these patients. We then present factors influencing prescription or non
      prescription of heart failure drugs and emphasize the importance of a team
      management programme and patients pathways.

PMID- 20684409
TI  - [Clinical inertia and treatment adherence in the management of chronic valvular
      heart diseases].
AB  - Valvular heart diseases are of increasing importance among the general adult
      population. When compared with other heart diseases, there are few trials in the
      field of valvular heart disease and randomized clinical trials are particularly
      scarce. Two sets of guidelines exist: one in the USA and the other in Europe.
      However, they are not always consistent due to the lack of randomized data and it
      appears that, frequently, there is a gap between the existing guidelines and
      their effective application.

PMID- 20684410
TI  - [Adherence to the rules for antithrombotic treatment in atrial fibrillation].
AB  - Adherence to the rules for antithrombotic ment in atrial fibrillation patients
      significantly reduces the risk of stroke. We review the criteria for the use of
      anti-vitamin K as well as its daily management in patients with atrial
      fibrillation.

PMID- 20684411
TI  - [Adherence to antiplatelet therapy in patients with coronary artery disease].
AB  - Clinical benefit of antiplatelet therapy is established for cardiovascular
      disease and percutaneous coronary intervention (PCI). Dual antiplatelet therapy
      is used to optimize platelet inhibition. However, cardiovascular events still
      occur. Aspirin/clopidogrel resistance and poor compliance are the main factors
      implied in recurrent events. Compliance to dual antiplatelet therapy is
      particularly relevant during the first 6 months following acute coronary
      syndromes and PCI. Furthermore, several studies have shown association between
      antiplatelet resistance and poor compliance. Additionally, late (1 month to 1
      year) and very late (> 1 year) stent thromboses are intimately linked to
      interruption of antiplatelet treatment. In this article we review the latest data
      about compliance, resistance and recommendations regarding antiplatelet therapy.

PMID- 20684412
TI  - [How to optimize lipid-lowering therapy: do not forget patient's non-compliance].
AB  - The pharmacological treatment of dyslipidaemia, essentially by statins, should
      take place in a global strategy of prevention of cardiovascular diseases.
      Treating a risk factor, asymptomatic by definition, which imposes an early
      constraint for a potential late benefit, exposes to patient's noncompliance.
      Besides physician's clinical inertia to initiate and adjust the lipid-lowering
      therapy in at risk patients, such lack of patient's compliance is one of the key
      elements that may explain the failure to reach or maintain therapeutic targets,
      and represents a major pharmacoeconomical concern. This article analyses first
      the main reasons explaining the poor compliance to lipid-lowering therapy and,
      then, describes some approaches to improve patient's adherence to medications in
      order to better prevent cardiovascular diseases.

PMID- 20684413
TI  - [Clinical inertia in the management of patients with type 2 diabetes: how to
      solve it?].
AB  - Although strict glucose control can prevent or delay the onset of complications
      in patients with diabetes, optimal control frequently is not achieved. A partial
      explanation for this phenomenon can be attributed to so-called clinical inertia
      of physicians, defined as "recognition of the problem but failure to act". Such
      therapeutic inertia may result from patient's reluctance, difficulties inherent
      to available treatments and physician's attitudes. Clinical inertia may be
      present at each successive step in the management of type 2 diabetes. This
      article describes some solutions to help physicians reducing therapeutic inertia
      and improving patient care.

PMID- 20684414
TI  - [Deleterious effects of lack of compliance to lifestyle and medication in
      diabetic patients].
AB  - The treatment of diabetes mellitus is complex and involves lifestyle modification
      to optimize nutrition and physical activity as well as the addition of
      pharmacological therapy to provide needed physiological support for insulin
      deficiency or for insulin resistance. Adherence to medical recommendations has
      been found to be associated with improved glycaemic control through HbA1c
      reduction but also to result in improved outcomes and reduced costs of diabetes.
      Despite this potential benefit of pharmacological therapy, adherence to glucose
      lowering treatments is poor, ranging from 36% to 85% adherence to oral
      medications. The most common factors affecting medication taking in diabetic
      patients include regimen complexity, dosing frequency greater than twice daily,
      cost, poor self-confidence, insufficient education about the use of the products,
      depression, and adverse effects or fear of them. Several barriers to medication
      taking have been suggested although well-controlled trials to confirm and resolve
      these barriers are limited yet. Further studies are needed to test specific
      interventions to improve medication taking in diabetes.

PMID- 20684415
TI  - [Perioperative tobacco cessation: a crucial period to overcome clinical inertia
      and poor compliance].
AB  - Smoking concerns 30% of the patients scheduled to anesthesia. Tobacco is one of
      the most important risk factors for postoperative complications. There are two
      classes of complications: those induced by the smoking habits on the
      cardiovascular and the respiratory systems, and those that predispose to other
      complications by direct interference with processes required for the success of
      surgery: healing and immune responses. The preoperative period represents a
      crucial period to overcome clinical inertia and profit of a better compliance.
      Some strategies applicable by the general practitioner and the anesthesiologist
      during the preoperative consultation to establish smoking cessation and help the
      patient to comply with are proposed.

PMID- 20684416
TI  - [Inertia and adherence as factors influencing asthma control].
AB  - Asthma is a chronic inflammatory disease which can be most often adequately
      controlled by current medications as demonstrated by multiple randomised clinical
      trials. Yet most of the recent surveys conducted in the real life setting point
      to an inadequate control in the majority of asthmatics. In addition to factors
      linked to the hygiene of life, clinician's inertia and patient's lack of
      adherence to the treatment certainly contribute to poor asthma control.

PMID- 20684417
TI  - [How to improve therapeutic compliance in the asthmatic pediatric patient].
AB  - Asthma is a chronic disease the control of which often requires a day-to-day
      treatment. The compliance in childhood asthma is estimated at 50%. It is
      therefore mandatory to resort to strategies for good compliance. Starting from a
      literature review and the concept of Guided Self-Management defined in the GINA
      2009 report, our pneumo-paediatric unit offers a local, useful and efficient
      strategy based on close collaboration with the family doctor, an Internet asthma
      school or DVD and the edition of a clear asthma treatment plan, which can easily
      be filled in by the physicians.

PMID- 20684418
TI  - [About the reticence to specific immunotherapy in alergic subjects].
AB  - The increasing number of allergic subjects and the alteration of their quality of
      life are major concerns of public health. Symptomatic treatments of allergic
      diseases are not always able to improve the patient's complaints. Allergic
      exploration aims to identify IgE-dependant mechanisms and subsequently to prove
      the responsibility of the detected allergen in the allergic disease. The efficacy
      of the specific immunotherapy (SIT) using allergens in either subcutaneous or
      sublingual forms has been proven in rhinitis, conjunctivitis, asthma and IgE
      induced reactions to hymenoptera venom. The lack of training in allergology is an
      important reticence of general practitioners and specialists to prescribe SIT.
      Furthermore, the duration of the treatment and its important cost in Belgium
      (where, only venom SIT is reimbursed by the Social Security) interfere
      significantly with the compliance of the patients.

PMID- 20684419
TI  - [Challenges to reduce mortality due to hepatitis C: improving accessibility to
      therapy and compliance].
AB  - Current therapies with pegylated interferon and ribavirin are effective to
      eradicate the virus C. Improvements are foreseen in the near future with
      combination of the current treatment with antiviral therapies (antiproteases,
      antipolymerases). Eradication of the virus, when obtained, has a favorable impact
      on an individual basis. However, to reduce the mortality related to the virus C
      at a population level, an important point is the accessibility to therapy. It has
      been calculated that the impact of current management to reduce mortality is
      minimal, as compared to the absence of treatment, due to a poor accessibility to
      therapy. To obtain a significant additional reduction of mortality, a better
      screening, a better access to the threatment are crucial.

PMID- 20684420
TI  - [Prevention and treatment of osteoporosis: avoiding clinical inertia and
      promoting therapeutic adherence].
AB  - Given the ageing of the population and the socio-economic burden of osteoporotic
      fractures, prevention and treatment of osteoporosis are a priority. A number of
      effective therapeutic agents have been developed, allowing a better management of
      postmenopausal osteoporosis. Despite the availability of these agents,
      osteoporosis remains underdiagnosed and a significant proportion of patients
      receive no treatment. The prevention of the first fracture constitutes one of the
      major concerns. Moreover, adherence to anti-osteoporosis medications remains
      poor. Long-term adherence to therapy is required for optimal therapeutic benefit
      for patients with osteoporosis. Adequate adherence to anti-osteoporotic treatment
      leads to abetter increase in bone mineral density and a significant reduction in
      risk of both vertebral and nonvertebral fractures. Consequently, therapeutic
      adherence must be a major concern for physicians managing osteoporosis. The
      extension of dosing intervals may be an element, among others, allowing to
      improve therapeutic adherence. The once monthly oral, quaterly or annual
      intravenous (bisphosphonates), or else subcutaneous, every 6 months (denosumab)
      formulations may potentially improve adherence.

PMID- 20684421
TI  - [Treatment compliance in epileptic patients. A frequent and complex problem].
AB  - Epilepsy is a chronic disease, requiring a medical treatment which is essentially
      preventive (avoiding further seizure). Because of these characteristics, 30 to
      50% of epileptic patients do not always comply with their treatment. In this
      paper, we review the different factors of poor compliance. Some are specific to
      this medical condition, while others are more general, like treatment complexity.
      We list some suggestions to improve the compliance of the epileptic patient in
      routine medical practice.

PMID- 20684422
TI  - [Recovering from depression: a matter of objective and determination].
AB  - Depression is a major public health problem. According to the World Health
      Organization (OMS), depression is currently the second cause of disability in
      developping countries. Depression is also one of the most frequent mental
      illnesses. In the treatment of depression, the main objective is to achieve
      complete remission and to prevent recurrence. Unfortunately, in clinical
      practice, this aim is particularly difficult to reach. Indeed, in clinical trials
      and in naturalistic studies, remission levels are rather low. Fortunately,
      different therapeutic strategies are available that increase chances to achieve
      remission. Therapeutic options such as switching, augmentation and combination
      are very effective. Some strategies are considered as more effective than others,
      but the choice is generally based on the experience of the clinician. Indeed,
      scientific data remain limited in the field of treatment resistant depression.
      Besides pharmacology, psychotherapy and cerebral stimulation techniques could be
      interesting alternatives.

PMID- 20684423
TI  - [Inertia or overtreatment in children. When sleeping time is disturbed in
      infants: how to improve the family's distress].
AB  - Sleeping disorders are frequently encountered in infants and adolescents. They
      often induce a distress in the family, an individual sadness possibly leaving at
      time to maltreatment. In the normal infant or the medically fragile infant due to
      prematurity or an acute episode, complaints from the patient or family sources
      force the medical team to find an explanation or a treatment, which are not
      always adequate. In other conditions such as asthma, obesity, anorexia nervosa,
      autism, cerebral palsy, hyperactivity, the sleeping disorders may be so unnoticed
      or remain insufficiently investigated. Globally, in this domain, the clinical
      description is often imprecise and sleep studies underused. A more accurate
      assessment should lead to a better educative approach and more appropriate
      therapy.

PMID- 20684424
TI  - [The therapeutic compliance in solid organ transplantation. The case of renal
      transplantation].
AB  - A successful transplantation implies that immunosuppressive drugs will have to be
      taken during the whole patient's life. Poor drug compliance is a multifactorial
      problem, that is particularly dangerous in organ transplantation as it can lead
      to loss of graft function and return to dialysis treatment. The medical doctor
      must stimulate the patient's adherence to the strict therapeutic drug protocol.
      The patient must also be reminded at each medical consultation of the importance
      of such rigorous drug intake. This bad (or non) compliance is particularly well
      demonstrated a long time after transplantation. The medical staff, all the health
      participants, but also the family members must continuously fight against non
      compliance, which is inherent to any chronic disease.

PMID- 20684425
TI  - [Therapeutic inertia in contraception].
AB  - The efficiency of contraception is linked to the method and the patient's
      compliance. The advice given by the physician about contraception use is
      essential to avoid unintended pregnancy. The accuracy of contraceptive choice and
      the individualized adaptation over time contribute to safe contraception.

PMID- 20684426
TI  - [Non-observance and therapeutic inertia in obstetrics].
AB  - Observance around pregnancy includes two parts: what can be done before
      conception and what must be done during pregnancy. Preconception care, if
      efficaciously performed, offerss real benefits for foetal and child development.
      Its efficacy will depends on the involvement and motivation of physicians and
      particularly also on the patient's observance. In this article we summarize
      essential pieces of advice to be given to each patient before pregnancy.
      Therapeutic inertia in obstetrics presents two differents aspects: on the one
      hand, the delay to initiate a therapeutic strategy when a complication arises
      such as a postpartum hemorrhage; on the other hand, the continuation of obsolete
      practices, such as the therapy of uterine hypersystolia.

PMID- 20684427
TI  - [Diabetes and pregnancy: impact of medical inertia and therapeutic compliance].
AB  - Pregnancy and infant outcomes are related to maternal blood glucose profile.
      Managing preexisting diabetes and achieving euglycaemia before and during the
      pregnancy reduce the risk for complications. Screening, diagnosis and treatment
      of gestational diabetes are important issues from a public health point of view,
      more particularly because of the progression of this disease due to obesity
      epidemics among young people. Pregnancy in a diabetic woman is a critical
      situation where neither clinical inertia nor patient's non-compliance could be
      accepted.

PMID- 20684428
TI  - [Adherence to long-term medication: the particular case of the adjuvant endocrine
      therapy for breast cancer].
AB  - The aim of adjuvant hormone therapy for breast cancer is to reach, in daily
      practice, an efficacy similar to that obtained in clinical trials. In spite of
      the demonstrated efficacy of hormone therapy, compliance represents a major
      challenge and a multidimensional problem. A better understanding of the reasons
      underlying non-compliance would help identify the patients at higher risk and
      would permit the implementation of strategies to improve compliance to adjuvant
      hormone therapy. With this in mind, we undertook a review of the recent
      literature on the topic (Pub Med 2003-2009).

PMID- 20684429
TI  - [Therapeutic observance in haematology: the particular case of chronic myeloid
      leukemia].
AB  - Therapeutic adhesion is essential because it modulates the efficiency of
      treatment, the occurrence of side effects and the socioeconomic costs possibly
      associated with it. In haematology, in the particular case of Chronic Myeloid
      Leukemia, the "ADAGIO" study performed by Noens and co-workers demonstrated that
      therapeutic observance is lower than the practitioners, the patients and the
      family members believe it is. This lack of adhesion can engender a decrease of
      the efficiency of treatment, in particular by imatinib. Factors such as the
      chronicity of the disease and the length of treatment modify therapeutic adhesion
      over time. Simple methods, addressing both the patient and the doctor should be
      developed to improve this therapeutic adhesion.

PMID- 20684430
TI  - [Diagnostic defects and therapeutic set-backs in hair disorders].
AB  - Hair loss, also called hair effluvium is often considered as an ancillary
      complaint. However, this situation is quite common in both genders. It is part of
      numerous clinical presentations in internal medicine and dermatology. Obviously,
      any correlation between a biologic abnormality and hair loss does not prove a
      relationship of causality. In absence of pathogenic diagnosis and causality
      criteria, chances are low to control adequately hair effluvium by a treatment
      given by the whims of fate. In addition, the risk and frequency of therapeutic
      inertia are increased. When the hair loss is not controlled and/or compensated by
      growth of new hairs, several types of alopecia inexorably develop.

PMID- 20684431
TI  - [Making strides facing "second flowering" syphilis papules].
AB  - In a recent past, the incidence of syphilis has increased in various geographical
      regions, particularly in urban areas. In addition, the disease is particularly
      associated with HIV infection. In secondary syphilis, the diagnosis may prove to
      be particularly difficult to reach because the clinico-pathological resemblance
      with other skin disorders is commonly high. The risk of diagnostic roaming is
      associated with therapeutic inertia which is highly prejudiciable to the patient.

PMID- 20684432
TI  - [When creams turn into a burden].
AB  - Topical treatment is the cornerstone of therapy for patients suffering from
      psoriasis. Its efficacy and safety have been demonstrated in a large number of
      publications. However, in daily life, the treatment outcome is often less
      satisfactory than the results published in the literature. This phenomenon is
      clearly linked to non-adherence. Indeed, patients with psoriasis frequently
      consider the topical therapies frequently as a heavy burden. The successful
      management of psoriasis with topical agents requires a perfect understanding
      between the patient and the practionner, which provides regular renewal of the
      patient's motivation.

PMID- 20684433
TI  - [Insecticides: DDT, DDE, DDD].

PMID- 20684434
TI  - [Professional eosinophilic bronchitis: considerations and new diagnostic methods
      in a clinical case].
AB  - Nonasthmatic eosinophilic bronchitis (NAEB) is a condition characterized by
      corticosteroid-responsive chronic cough, sputum eosinophilia and absence of
      symptoms or objective evidence of variable airflow obstruction and airway hyper
      responsiveness. Like asthma, NAEB can be associated with exposure to occupational
      sensitizers and can be considered as being a variant of occupational asthma when
      it develops as a consequence of work exposure. Few case reports of NAEB caused by
      workplace exposure have been reported. Bakers are at high risk of developing
      occupational respiratory disorders and three cases of occupational NAEB have been
      described. We describe the first case of occupational NAEB due to storage mites
      in a baker in which the offending agent was identified by means of the basophil
      activation test (BAT), a new tool which has never been proposed in diagnostic
      procedures of occupational respiratory allergy. BAT's results allowed the
      recognition of the offending agent, that is mandatory for diagnosis.

PMID- 20684435
TI  - [Pulmonary concentration of asbestos fibers in steel workers with pleural
      mesothelioma].
AB  - The asbestos fibre burden of the lung has been used in the past as a biological
      indicator of cumulative exposure to the mineral so much so that in 1997 reference
      limits even for non-occupationally exposed people have been proposed. This kind
      of analysis was performed on groups of workers of different type of industries
      and allowed to achieve a qualitative-quantitative estimate of past exposure to
      asbestos, even in absence of exposure estimates by environmental monitoring. An
      important example is the steel industry where asbestos was widely used in the
      past, but for which there are not available exposure estimates of workers. Among
      the mesothelioma cases collected by the Mesothelioma Registry of the Province of
      Brescia from 1980 to present there are 55 workers who spent at least 5 years in
      steel industry, on a total of 289 cases classified as asbestos exposed (19%). For
      8 subjects who worked in steel mills and production of electrical steel pipes, of
      which 4 in the same plant, lung tissue samples were available for the asbestos
      fibres burden analysis (7 samples coming from autopsies and 1 from extra-pleural
      pneumonectomy). In all cases the diagnosis was given with histological analyses
      supplemented with immunohistochemistry. In 7 cases autopsied the diagnosis was
      confirmed. The work histories have been reconstructed in detail through the
      interview process, inclusive of details of duties performed. The asbestos fibre
      burden analyses showed a range of concentrations between 260,000 and 11,000,000
      ff per grams of dry tissue; the concentration of amphiboles was much higher than
      that of chrysotile. The highest body burden was detected in the maintenance
      workers of the same plant in witch a cluster of malignant mesothelioma was
      observed. In conclusion, this study illustrates the results of asbestos fibres
      burden analyses in subjects where exposure to asbestos is sure but not
      quantifiable. The results showed also that these concentrations can reach values
      that overlap with those found in asbestos-cement workers and in asbestos-textile
      workers. These data suggest to consider the cases of mesothelioma occurred in the
      steel workers at least as "possible" exposure, even in the absence of adequate
      information on the circumstances of contact with asbestos. This study, although
      based on a small number of cases, is the only one ever held in Italy on workers
      in this sector.

PMID- 20684436
TI  - [Algorithm for assessment of exposure to asbestos].
AB  - There is no universally approved method in the scientific literature to identify
      subjects exposed to asbestos and divide them in classes according to intensity of
      exposure. The aim of our work is to study and develope an algorithm based on the
      findings of occupational anamnestical information provided by a large group of
      workers. The algorithm allows to discriminate, in a probabilistic way, the risk
      of exposure by the attribution of a code for each worker (ELSA Code--work
      estimated exposure to asbestos). The ELSA code has been obtained through a
      synthesis of information that the international scientific literature identifies
      as the most predictive for the onset of asbestos-related abnormalities. Four
      dimensions are analyzed and described: 1) present and/or past occupation; 2) type
      of materials and equipment used in performing working activity; 3) environment
      where these activities are carried out; 4) period of time when activities are
      performed. Although it is possible to have informations in a subjective manner,
      the decisional procedure is objective and is based on the systematic evaluation
      of asbestos exposure. From the combination of the four identified dimensions it
      is possible to have 108 ELSA codes divided in three typological profiles of
      estimated risk of exposure. The application of the algorithm offers some
      advantages compared to other methods used for identifying individuals exposed to
      asbestos: 1) it can be computed both in case of present and past exposure to
      asbestos; 2) the classification of workers exposed to asbestos using ELSA code is
      more detailed than the one we have obtained with Job Exposure Matrix (JEM)
      because the ELSA Code takes in account other indicators of risk besides those
      considered in the JEM. This algorithm was developed for a project sponsored by
      the Italian Armed Forces and is also adaptable to other work conditions for in
      which it could be necessary to assess risk for asbestos exposure.

PMID- 20684437
TI  - [Risk assessment for upper extremity work related muscoloskeletal disorders in
      different manufactures by applying six methods of ergonomic analysis].
AB  - BACKGROUND AND OBJECTIVES: The risk assessment for Upper Extremities Work Related
      Muscle skeletal Disorders (UEWMSDs) remains a complex and open question. For
      professionals involved in this analysis of fundamental importance appears the use
      of technical/good practice norms or the guide lines produced by scientific
      society or association, such as for our country the guide lines published on this
      theme by the Italian Society of Occupational Medicine and Industrial Hygiene
      (SIMLII). The objective of this research was to verify and validate the multiple
      step method suggested by above mentioned guide lines and to compare results
      obtained by six analysis methods adopted (Washington State Standard, OCRA, HAL,
      RULA, OREGE and STRAIN INDEX (SI)). METHODS: 439 workstation in 17 manufactures
      employing 4166 workers for a total of 1396 analysis by different methods were
      considered, by adopting the following multiple step procedure: preliminary
      evaluation by Washington State method and OCRA checklist in all the working
      stations, RULA or HAL as first level evaluation, OREGE or SI as second level
      evaluation when complexity of work variables or contradictory results emerged. We
      have also collected data, provided by occupational physicians, about the
      pathologies of the upper limb. A representative sample of workers was also
      administered a INRS OREGE questionnaire that investigates the disorders of the
      upper limb, the subjective perception of risk, psychosocial factors and stress
      related disturbs. RESULTS: The preliminary evaluation resulted negative (risk
      absent) in the 87% of examined work stations and by using checklist OCRA optimal
      acceptable condition was found in 57% (the percentage reaches more than 90% when
      classes of risk absent-very low-low risk classes of the method were considered
      all together), by HAL in 91% of analysis, by RULA in 90%, by OREGE in 58%; by SI
      in 67% of examined working position. Five methods have been contemporary used for
      31 working position with the following results: 58% at different degree of risk
      by OCRA, 13% by HAL, 19% by RULA; 13% by OREGE; 10% by SI. Among the main
      components of the bio mechanical risk the high frequency of working task resulted
      at first place for 4/5 methods and for checklist OCRA also the evaluation of
      recovery times. Consistent with the findings from risk assessment, the majority
      of reports of occupational diseases by occupational physician is localized at the
      wrist and workers assigned to tasks at risk not always have had occupational
      diseases. The role of main psychosocial factors was demonstrated in about the 15
      20% of working conditions and regarded in particular the working climate, the job
      maintenance perspective, the time pressure and errors possibility together with
      the difficulty of help by colleagues and managers and stress related disturbs.
      DISCUSSION AND CONCLUSION: The preliminary evaluation by State of Washington
      method appears to be an adequate instrument for identify the working condition at
      risk. The results of this method appears well correlated with OCRA checklist and
      HAL. The risk conditions were always confirmed by higher complexity methods
      (RULA, OREGE, SI). All the adopted methods were in a good agreement in two
      extreme situations: high risk or absent risk. In the degree of accordance varied
      on the basis of their rationale and of the role of their different components. A
      necessary integration of biomechanical analysis appears the evaluation of working
      conditions and musculoskeletal and psychological disorders collected directly
      from the workers and the results of health surveillance programs. The
      recommendations of SIMLII about the critical use of biomechanical methods and
      about the possible use of more than one of them considering the working
      characteristics have been confirmed.

PMID- 20684438
TI  - [Smoking in the workplace: role of occupational physicians].
AB  - In many industrialized countries smokers have been observed in high prevalence
      among workers with poor educational status, who are usually exposed to major
      occupational risks. The smoking habit and passive smoking may by themselves, or
      through interactions with other occupational risk factors, cause the onset of
      serious diseases. Therefore health reasons and the legal obligation to observe
      the smoking ban in the workplace make it essential to prevent and combat smoking
      in the workplace and to promote smoking cessation in workers who smoke. This
      initiative should benefit not only workers' health and well-being but also
      company finances. The Occupational Physician should engage in diverse activities
      ranging from encouraging young people not to start smoking to providing
      programmes to encourage workers who smoke to abandon the habit. For example, he
      or she should i) inform managers, supervisors and workers about the high risks
      linked to smoking, passive smoking and obligations established by law ii) collect
      information about the smoking habit among workers and supply workers with the so
      called minimal clinical intervention during routine health surveillance
      appointments and iii) collaborate with specific health promotion programmes in
      the workplace.

PMID- 20684439
TI  - Edentulism as part of the general health problems of elderly adults.
AB  - Though the prevalence of edentulism has decreased over the last decades, there
      will be a relevant proportion of edentulous individuals in the ageing societies
      worldwide. The impact of edentulism on daily oral function and social
      interactions has significant plausibility and has been described using multiple
      dimensions. However, evidence of general health associated with complete tooth
      loss is limited. To highlight the importance of oral health to general wellbeing
      and its interrelated dependencies this article reviews international literature
      on the psychological and physiological aspects of edentulism, particularly on
      Oral Health Related Quality of Life (OHRQoL), nutrition aspects as well as
      morbidity and mortality.

PMID- 20684440
TI  - Fluorides leaching from restorative materials and the effect on adjacent teeth.
AB  - OBJECTIVE: Placing a Class II restoration in a tooth changes the local
      environment, including that for the adjacent tooth. Apart from the change to a
      less- or non-cariogenic environment for the restored tooth, the effect of
      leachable components from a restoration in the adjacent tooth should be taken
      into consideration. METHOD: Practice-based clinical studies comprising of 1341
      unrestored proximal surfaces in contact with Class II restorations using
      different restorative materials were reviewed to assess the effect on the caries
      development on the adjacent teeth. The caries status of the adjacent un-restored
      proximal surface was assessed as being clinically sound, having active caries
      with or without cavitation, or having arrested caries. Restorations from nine
      clinicians were reviewed. They had attended annual meetings where all aspects of
      the investigation had been discussed. The surfaces were followed for up to eight
      years. RESULTS: A reduced rate of caries development and progression were found
      on surfaces in contact with fluoride releasing materials like glass ionomers,
      resin modified glass ionomers and compomers compared to surfaces in contact with
      amalgam. CONCLUSION: Fluoride releasing materials reduce the development and
      progression of primary caries on adjacent proximal surfaces.

PMID- 20684441
TI  - Periodontitis in 65-74-year-old victims in Wenchuan, China post-earthquake:
      implications for service provision.
AB  - OBJECTIVES: One year after the Wenchuan, Southwest China earthquake, a cross
      sectional study was conducted as a preliminary assessment of the periodontitis of
      65- to 74-year-old victims and to compare it with survey data from before the
      earthquake. METHODS: A temporary housing, community-based study was conducted. A
      total of 1495, 65-74-year-old subjects, 740 county and 755 rural, 753 men and 742
      women, were included in the study. The data were collected by means of an
      interviewer-administered questionnaire and an oral examination. RESULTS: The
      calculus and gingival bleeding were distinctly increased, and the prevalence of
      Attachment Loss at 4-5 mm of 77.3%, at 6-8 mm of 44.8%, at 9-11mm of 13.6% and at
      > or =12 mm of 2.7%, were also much higher than the findings before the
      earthquake. Additionally, oral hygiene practice, stress, tobacco abuse and
      nutritional intake had gone into an adverse trend after the earthquake.
      CONCLUSION: The changes caused by the earthquake exacerbated periodontitis in
      older people. Therefore, consistently superior oral prevention and treatment
      service programmes for elderly victims should be constituted and encouraged
      throughout the temporary housing community.

PMID- 20684442
TI  - The impact of visible dental decay on social judgements: comparison of the
      effects of location and extent of lesion.
AB  - BACKGROUND: Previous research has established that people can make social
      judgements about someone else based on the condition of that person's teeth. The
      characteristics of visible tooth decay, with respect to the effect on such social
      judgements, have not, however, been subject to extensive investigation. This
      study sought to determine whether the position of visible decay and/or the extent
      of the lesion are determining factors in such social judgements of each other.
      METHOD: In a between subjects design, 100 young people were randomly divided into
      4 groups of 25 and each group shown a differently computer-modified photograph of
      the same person. Extent and location of the lesion were varied systematically.
      Participants were asked to rate the person in the photograph with respect to
      intellectual ability, social competence and psychological adjustment. The scores
      from those questions were analysed with one way analysis of variance (ANOVA) then
      Tukey's HSD where ANOVA revealed significant differences. RESULTS: The data
      confirmed previous studies that have shown that poor dental condition is highly
      correlated with perceived poor social performance and intellectual ability.
      Further, the data showed that with respect to the constructs of intellectual
      ability, extraversion and care for one's personal appearance, a more central
      position of caries is more predictive of poor social judgements than just the
      presence of visible decay, or even twice the amount of decay. We discuss the
      possible evolutionary and ontological reasons for making social judgements that
      are influenced by a person's dental health as well as considering the
      implications of our findings for dentists.

PMID- 20684443
TI  - Superiority of an essential oil mouthrinse when compared with a 0.05%
      cetylpyridinium chloride containing mouthrinse: a six-month study.
AB  - OBJECTIVE: To evaluate the antiplaque/antigingivitis effectiveness of an
      essential oils containing mouthrinse as compared to a 0.05% cetylpyridinium
      chloride mouthrinse. METHOD: Generally healthy subjects with mild to moderate
      levels of plaque and gingivitis participated in a 6-month, examiner-blind, single
      centre, randomised, parallel-group controlled clinical trial. They were
      randomised into three mouthrinse groups--control (C), 0.05% cetylpyridinium
      chloride (CPC), or a fixed combination of essential oils (EO). Subjects received
      a dental prophylaxis at baseline and rinsed twice daily in addition to their
      usual oral hygiene for six months. Plaque Index and Modified Gingival Index were
      determined at 3 and 6 months. RESULTS: At 6 months, the EO group exhibited
      statistically significantly lower mean scores for MGI and PI than CPC (32.4% and
      56.2% reductions, respectively). Compared to control, EO provided statistically
      significantly lower mean MGI and PI scores (36.3% and 69.7 %, respectively). The
      CPC group showed statistically significantly lower mean MGI and PI scores than
      the C group (5.8% and 30.7%, respectively). CONCLUSION: This study demonstrated
      the superiority of an EO rinse compared to a 0.05% CPC rinse in reducing plaque
      and gingivitis and confirmed that the daily use of an EO containing mouthrinse
      can provide a clinically significant benefit in reducing plaque and gingivitis.

PMID- 20684444
TI  - Compliance with infection control recommendations in South African dental
      practices: a review of studies published between 1990 and 2007.
AB  - In a country where the prevalence of infectious diseases ranks among the highest
      in the world, infection control in health care facilities should not be
      debatable. This unfortunately does not seem to be the case in South African oral
      health care facilities. This study is a systematic review of available literature
      on the adherence of South African oral health care professionals to infection
      control recommendations. Nine focus areas were investigated with regard to
      infection control practices: knowledge of infectious occupational hazards;
      personal hygiene and care of hands; correct application of personal protective
      equipment; use of environmental barriers and disposable items; sterilisation
      (recirculation) of instruments and handpieces; disinfection (surfaces) and sound
      housekeeping; management of waste disposal; quality control of dental unit
      waterlines, biofilms and water; as well as other special considerations. Although
      South African studies are limited and most of them relied on self-reports, which
      could have resulted in a serious overestimation of compliance, even these studies
      indicate serious shortcomings with regard to infection control practices in oral
      health care facilities in this country. This review highlights opportunity for
      improvement. Furthermore, it identifies possibilities for future research in
      infection control and also opportunities to improve infection control education
      for all oral health care workers in the country.

PMID- 20684445
TI  - Trends in demand for general anaesthetic care for paediatric caries in Western
      Australia: geographic and socio-economic modelling of service utilisation.
AB  - AIMS: This study aimed to assess the temporal and spatial changes in the demand
      for general anaesthesia, relative to disease incidence, in 0-19-year-olds.
      METHODS: Hospitalisation data were obtained from the Western Australian Morbidity
      Data System for the financial years 1999/2000 to 2004/2005, and principal
      diagnosis was obtained from every patient discharged from a public or private
      hospital. Hospitalisation data was correlated with socioeconomic status and the
      geographical location of primary residence. RESULTS: In the public hospital
      sector, there were greater rates of people residing in Statistical Local Areas
      (SLAs) with decreasing accessibility to healthcare services utilising the option
      of treatment of dental caries under general anaesthetic (GA) compared to people
      living within highly accessible areas. In the private sector, children who
      resided in SLAs with the greatest access to healthcare facilities had a greater
      rate of being hospitalised for the treatment of dental caries under GA.
      CONCLUSIONS: The results demonstrated distinct patterns of trends in demand for
      general anaesthetic care among different SES groups and geographical location of
      primary residence. There was an overall emerging trend of increasing demand
      placed on public sector both among dental care users among high and low SES.
      Moreover, the results demonstrated the potential application of geographic
      modelling as a service planning tool for estimating the future demand for GA care
      for dental caries in addition to the timely need for focused attention on
      preventive services for early identification, prevention and control of dental
      caries among children.

PMID- 20684446
TI  - Veteran suicide prevention: emerging priorities and opportunities for
      intervention.

PMID- 20684447
TI  - Fostering closer alignment of the Veterans Health Administration and the Indian
      Health Service.

PMID- 20684448
TI  - Evaluation of the NATO Disease Surveillance System by its users in Kosovo in
      2008.

PMID- 20684449
TI  - Disease and nonbattle injuries sustained by a U.S. Army Brigade Combat Team
      during Operation Iraqi Freedom.
AB  - BACKGROUND: A longitudinal cohort analysis of disease nonbattle injuries (DNBI)
      sustained by a large combat-deployed maneuver unit has not been performed.
      METHODS: A descriptive analysis was undertaken to evaluate for DNBI casualty care
      statistics incurred by a U.S. Army Brigade Combat Team (BCT) during a
      counterinsurgency campaign of Operation Iraqi Freedom. RESULTS: Of the 4,122
      soldiers deployed, there were 1,324 DNBI with 5 (0.38%) deaths, 208 (15.7%)
      medical evacuations (MEDEVAC), and 1,111 (83.9%) returned to duty. The DNBI
      casualty rate for the BCT was 257.0/1,000 soldier combat-years. Females, compared
      with males, had a significantly increased incidence rate ratio for becoming a
      DNBI casualty 1.67 (95% CI 1.37, 2.04). Of 47 female soldiers receiving MEDEVAC
      35 (74%) were for pregnancy-related issues. Musculoskeletal injuries (50.4%) and
      psychiatric disorders (23.3%) were the most common body systems involved with
      DNBI casualties. Among the BCT cohort the psychiatric DNBI casualty rate and
      suicide rate were 59.8 and 0.58 per 1,000 soldier combat-years. The BCT cohort
      incidence rates for common musculoskeletal injuries per 1,000 combat-years were
      as follows: ankle sprain 15.3, anterior cruciate ligament rupture 3.3 and
      shoulder dislocation 1.2. CONCLUSIONS: Musculoskeletal injuries and psychiatric
      disorders accounted for 74% of the total DNBI casualties, and 43% of the DNBI
      casualties requiring subsequent MEDEVAC. The BCT cohort had a suicide rate nearly
      four times greater than previously reported, and selected musculoskeletal injury
      incidence rates were fivefold greater than the general population.

PMID- 20684450
TI  - Evaluation of the Military Acute Concussion Evaluation for use in combat
      operations more than 12 hours after injury.
AB  - The diagnosis and management of concussion can be difficult in a combat
      environment, especially in the absence of loss of consciousness or post-traumatic
      amnesia. As no validated test exists to diagnose or grade neurocognitive
      impairment from a concussion, the military currently employs the Military Acute
      Concussion Evaluation (MACE) in Iraq. This is a two-part test, which incorporates
      the standardized assessment of concussion (SAC) as its objective score, although
      it has not been shown to be valid unless administered shortly after injury. A
      research team deployed to Iraq between January and April 2009 to examine the
      validity of several tests of neurocognitive function following a concussion,
      including the MACE. When administered more than 12 hours after the concussive
      injury, the MACE lacked sufficient sensitivity and specificity to be clinically
      useful.

PMID- 20684451
TI  - Unit cohesion and PTSD symptom severity in Air Force medical personnel.
AB  - Research suggests that military unit cohesion may protect against the development
      of post-traumatic stress disorder (PTSD). However, equivocal findings have led
      researchers to hypothesize a potential curvilinear interaction between unit
      cohesion and warzone stress. This hypothesis states that the protective effects
      of cohesion increase as warzone stress exposure intensifies from low to moderate
      levels, but at high levels of warzone stress exposure, cohesion loses its
      protective effects and is potentially detrimental. To test this theory, we
      conducted a test for curvilinear moderation using a sample of 705 Air Force
      medical personnel deployed as part of Operation Iraqi Freedom. Results did not
      support the curvilinear interaction hypothesis, although evidence of cohesion's
      protective effects was found, suggesting that unit cohesion protects against PTSD
      regardless of level of stress exposure.

PMID- 20684452
TI  - Stress Gym: Feasibility of deploying a web-enhanced behavioral self-management
      program for stress in a military setting.
AB  - Stress and depression can adversely impact the performance of military personnel.
      Cognitive-behavioral (CBT) interventions for managing stress are efficacious in
      traditional face-to-face formats, but the Internet supports a broader reach of
      these programs. This study reports on the feasibility of using an Internet-based
      self-help stress-management intervention in military personnel. There were 142
      officers/enlisted sailors at a Naval Medical Center who completed the program.
      Evaluation of the program titled "Stress Gym" was positive for the user
      interface, content, feasibility, and satisfaction. Positive evaluation was not
      influenced by rank/status, sex, or previous deployment. Stress ratings also
      decreased significantly while using the program. These data support Stress Gym as
      being an online CBT-based self-help intervention that is feasible to deploy,
      accepted by the intended end users, and demonstrates the intended goal of
      reducing stress.

PMID- 20684453
TI  - Utilization of psychiatric services by female military personnel changes since
      admission of women to all German Armed Forces military careers.
AB  - OBJECTIVE: In 2001, women were admitted to all military careers in the German
      Armed Forces. This study examines whether the utilization of psychiatric services
      of female military personnel has changed since then. METHODS: The central medical
      database of German military personnel for the years 2000 and 2006 was analyzed.
      RESULTS: Between 2000 and 2006, the percentage (based on the average totals of
      male and female military personnel) of consultations of primary care unit
      surgeons for psychiatric problems increased significantly for both male and
      female military personnel, this increase being more apparent for women than for
      men. Stress-related disorders showed the greatest rise. In 2006, as opposed to
      2000, the total proportion of both outpatient and inpatient mental health
      treatment provided to female military personnel was significantly higher than for
      males, particularly regarding stress-related, affective and personality
      disorders. CONCLUSIONS: Gender-specific aspects should be considered more
      intensely in preventive and therapeutic psychiatric supply in the German Armed
      Forces.

PMID- 20684454
TI  - So you think you're bulletproof: Development and validation of the Invincibility
      Belief Index (IBI).
AB  - Risk-taking propensity can be influenced by sensation-seeking traits and self
      perceived invincibility. We hypothesized that the latter factor may reflect a
      stable trait that endures across situations and may influence risk-taking
      behavior. We developed and validated a 20-item scale, the Invincibility Belief
      Index (IBI) to measure this construct. The IBI demonstrated good internal
      consistency and excellent test-retest reliability in the development sample (n =
      100) and sustained similar levels of reliability in a cross-validation sample (n
      = 74). Principal components analysis yielded three orthogonal factors measuring
      self-perceived impunity (immunity from consequences), boldness/audacity (self
      assuredness and competitiveness), and adroitness (mental agility and survival
      skill). In the prediction of risk taking, IBI scores contributed additional
      unique variance beyond sensation-seeking scores alone. IBI scores demonstrated
      convergent and discriminant validity with concurrently administered measures.
      These preliminary results support the reliability and validity of the IBI as a
      brief measure of self-perceived vulnerability-invincibility in the face of
      adversity.

PMID- 20684455
TI  - One Shot-One Kill: a culturally sensitive program for the warrior culture.
AB  - Despite efforts to reduce the stigma of mental health services across branches of
      the United States military, lasting change among this warrior culture remains an
      uphill battle. Difficulty affecting change can be attributed in part to stigma
      associated with psychological services and largely, mental health providers'
      difficulty tailoring traditional models of treatment to military personnel. We
      will discuss the development of One Shot - One Kill (OSOK), a culturally
      sensitive mental health prevention program piloted to reduce stigma and improve
      help seeking behaviors among the warrior culture. Three hundred and twenty
      military members completed the OSOK performance enhancement and resiliency
      program piloted at Tallil, Iraq in 2008. Pilot data were collected to assess
      military members' perceptions of the training program. Results indicated positive
      responses demonstrating the OSOK program as a culturally sound program that could
      increase help seeking behaviors among military members.

PMID- 20684456
TI  - Case study of six-year follow-up of Navy survivors of a multiple fatality fire at
      sea.
AB  - This case study reports on the mental health of survivors of a multiple fatality
      fire at sea in an Australian Navy ship. Survivors were screened on three
      occasions after the fire with the Impact of Events Scale-Revised (IES-R) or Post
      Traumatic Check List-Civilian version (PCL-C), and once with the General Health
      Questionnaire, 28-Item version (GHQ-28), and the Alcohol Use Disorders
      Identification Test (AUDIT). Rates of possible disorders are discussed, along
      with comparisons with similar samples, and stability of possible post-traumatic
      stress disorder (PTSD) over time. While limited in size, the sample of this study
      contributes to the relatively small body of literature regarding the course of
      posttraumatic mental health in military personnel exposed to noncombat trauma.

PMID- 20684457
TI  - A usability assessment of AHLTA in ambulatory clinics at a military medical
      center.
AB  - The investigators conducted a formal usability evaluation of the military's
      electronic health record known as Armed Forces Health Longitudinal Technology
      Application (AHLTA). Seventeen providers from different specialties in the
      ambulatory setting were interviewed and observed at a military medical center.
      Data were analyzed by human factors experts. Observations and interviews yielded
      four major usability findings: (1) limited AHLTA use during the actual encounter,
      (2) difficulties in obtaining situational awareness of the patient, (3) work
      arounds with nonintegrated systems, and (4) frustrations in the use of the
      structured documentation. This assessment is congruent with usability concerns
      voiced in other military health system (MHS) and nonmilitary clinical systems.
      Improving the usability of future MHS clinical systems could lead to improved
      clinical decision making, patient safety, and increased information accuracy.

PMID- 20684458
TI  - The role of screening electrocardiograms in the evaluation of ROTC cadets
      applying for flight status.
AB  - The majority of sudden, nontraumatic deaths in young, otherwise healthy
      individuals result from an unknown underlying cardiac abnormality. The low
      sensitivity of the traditional history and physical exam in detecting these
      anomalies has led to a debate regarding the use of routine screening
      electrocardiograms (ECGs) in young adults. The present study screened 1,099 ROTC
      cadets applying for aviator status during the summers of 2005 and 2006. Seven
      candidates (0.6%) were disqualified because of ECG abnormalities, including two
      with Wolf Parkinson White syndrome. None of the individuals were identified by
      history and physical exam. ECG was an effective screening tool for detecting
      silent abnormalities with potential for arrhythmia in our population of healthy
      young adults. Other ECG findings indicative of anatomic abnormalities were not
      found. ECG screening can be a valuable tool and should be used in evaluating
      certain subsets of the population.

PMID- 20684459
TI  - Decreasing outpatient cardiac catheterization rates associated with cardiology
      clinic volume but not with increasing cardiac computed tomography utilization.
AB  - Cardiac computed tomographic angiography (CTA) is an accurate noninvasive test
      for diagnosing coronary artery disease (CAD). To investigate whether increasing
      use of CTA is correlated with left heart catheterization (LHC) rates, we
      performed a retrospective review of existing outpatient and inpatient
      catheterization lab and CTA electronic medical records from July 1, 2004 to June
      30, 2008. Comparing the previous 2 years (July 2004-June 2006) to the 2 years
      after addition of CTA (July 2006-June 2008), monthly LHC rates decreased 20 +/-
      6% (p = 0.08) and percutaneous coronary intervention (PCI) rates decreased 47 +/-
      6% (p<0.001). Cardiology clinic volume declined 34%. CTA rates increased 64 +/-
      7% (p<0.001). Radionuclide myocardial perfusion scan (MPS) usage remained stable.
      Despite increased utilization over the past 2 years, CTA was not correlated with
      significantly reduced LHC rates. The decline of outpatient LHC rates at our
      institution over 4 years is mainly influenced by decreasing outpatient Cardiology
      clinic volume.

PMID- 20684460
TI  - Complementary and alternative medicine use among military family medicine
      patients in Hawaii.
AB  - Complementary and alternative medicine (CAM) is a growing component of medicine
      within the U.S. civilian and military populations. Tripler Army Medical Center
      (TAMC) Family Medicine Clinic represents an overseas medical facility stationed
      among a diverse ethnic population. The impact that local cultures have on CAM
      utilization in the military population in overseas medical facilities is unknown.
      METHODS: Cross-sectional survey. The authors surveyed all volunteer soldiers,
      family members, and retirees 18 years old or greater enrolled at TAMC Family
      Medicine Clinic with appointments between September 1 and September 25, 2008.
      RESULTS: 503 volunteers were surveyed with a response rate of 73% (n = 369). A
      total of 50.7% reported using at least one CAM therapy within the last year. CAM
      use was significantly higher among women, Caucasians, and a college level
      education or greater. CONCLUSION: Prevalence of CAM use is higher within a
      military family medicine clinic in Hawaii than the prevalence among mainland
      civilian or other military populations.

PMID- 20684461
TI  - Trauma evaluation of the parotid duct in an austere military environment.
AB  - Evaluation of the parotid duct from trauma in an austere military environment can
      be challenging. Appropriate radiologic evaluation of a potential isolated parotid
      duct injury in this environment has not been reported. The use of a plain X-ray
      sialogram at the forward surgical team is demonstrated and may be beneficial in
      this setting.

PMID- 20684462
TI  - Radiology corner. Tight left upper lobe collapse from lung cancer.

PMID- 20684466
TI  - [Emergency medico-psychological units, beyond cliches].

PMID- 20684467
TI  - [Immediate intervention of medico-psychological emergency units].
AB  - Medico-psychological emergency units (CUMP) are part of the emergency medical
      assistance services. They are adapted to the early treatment of people suffering
      from the psychological effects of an intentional or accidental disaster.
      Immediate intervention implies the rapid setting up of a system adapted to the
      context and to the clinic.

PMID- 20684468
TI  - [Psychological debriefing and post-immediate psychotherapeutic intervention].
AB  - Psychological debriefing is a controversial treatment technique. In principle,
      many such treatments exist based on apparently indisputable conclusions which
      only assess the personal traumatic effect and neglect the collective impact,
      which is the original reason for the creation of this technique. Therefore, it is
      essential to take a look at the way in which debriefings are conducted, its
      indications, its limits and the psychodynamic processes at play.

PMID- 20684469
TI  - [Care in the very first moments in the event of traumatic loss].
AB  - The importance of managing the family circle in the event of violent death has
      been underestimated for many years. Only the reanimation of these patients in
      vital distress has been defined clearly. The training and information of pre
      hospital emergency staff in recent years has helped to make considerable headway
      in professional practices on this subject.

PMID- 20684470
TI  - [Taking care of the families of air disaster victims].
AB  - The medico-psychological emergency unit in Seine-Saint-Denis (93) was involved in
      managing the families of the victims of the AF447 flight crash which took place
      on the night of 31 May and 1 June 2009 between Rio de Janeiro (Brazil) and Paris.
      It is interesting to study the system set up at the airport, the symptomatology
      observed, and the parameters of the efficiency of the care provided.

PMID- 20684471
TI  - [Care for young children who have suffered a tragic event].
AB  - Children are regularly faced with traumatic events, whether these are disasters
      (tsunami, floods, earthquakes), accidents (transport, domestic) or intentional
      acts (war, ill treatment). The care provided for young Haitian children following
      the earthquake in January 2010 offers an insight into specific intervention
      methods, the treatment of post-traumatic disorders and the effects of trauma on
      those working with them.

PMID- 20684472
TI  - [Adapting treatments in therapeutic foster care].
AB  - Therapeutic foster care is a specific full-time hospitalisation method. It is
      designed to treat people of all ages suffering from mental problems within a
      stable substitutive family environment, in particular with a view to rebuilding
      their relational and autonomy skills. The acknowledgement by care staff and
      families of the patient's viewpoint and demands helps to adapt relational
      practices.

PMID- 20684473
TI  - [2/7. Home visits].

PMID- 20684474
TI  - [Sectorization and staff education in psychiatry].

PMID- 20684475
TI  - Progress in the molecular methods for the detection and genetic characterization
      of Cryptosporidium in water samples.
AB  - Cryptosporidium, the protozoan parasite, has several transmission routes,
      including anthroponotic and zoonotic transmission, as well as the foodborne way,
      but mainly by water. The oocysts, the resistant stage produced by
      Cryptosporidium, are remarkably stable, and can survive for weeks or even months
      in the environment. Furthermore, the infective dose is low, probably even a
      single oocyst can cause infection. The Cryptosporidium genus includes at least 16
      species; nevertheless, only a few can cause cryptosporidiosis, an intestinal
      disease in human and domestic mammals. Thus, the genetic characteristics of
      different Cryptosporidium species became fundamental in the diagnosis,
      monitoring, prevention and control of infections caused by this pathogen.
      Unfortunately, the traditional phenotypic techniques meet with difficulties in
      the specific diagnosis of cryptosporidiosis, therefore the new molecular tools
      must be applied. The RT -qPCR method can be used to differentiate viable and dead
      Cryptosporidium oocysts, and the LAMP assays have advantages for detection of
      organisms at relatively low concentration in environmental samples; however, the
      NAS BA assay specifically detects as few as one oocyst of a viable human
      pathogenic Cryptosporidium species. Reverse line blot hybridization (RL B) has
      been successfully used for specific identification and for differentiation of
      Cryptosporidium species. Described techniques are the most promising methods for
      the sensitive and accurate detection, but require a considerable selection of
      appropriate tools, genetic markers and analytical techniques for interpretations
      of database. However, the applicability of most of these methods to detect
      Cryptosporidium species or genotypes from environmental samples needs to be
      evaluated and standardized.

PMID- 20684476
TI  - Organic dust induced pulmonary disease - the role of mould derived beta-glucan.
AB  - The objective of the study was to evaluate the role of the mould cell wall agent
      beta-glucan in environmentally related pulmonary disease. All published articles
      where beta-glucan was administered by the airways, either as intratracheal
      injection or as inhalation were utilised as data sources. Data reporting
      consisted of analysis of data reports concerning the effects of beta-glucan on
      the immune system on the cellular level, particularly on the aggregation of
      inflammatory cells or production of inflammatory cytokines. High doses of soluble
      and particulate beta-glucan cause an inflammatory response characterized by
      cytokine activation and neutrophil invasion in the lung tissue. At lower doses,
      closer to environmental exposure levels, the predominant effect is an influence
      on the response to antigens, the reactivity of eosinophils and other Th2 driven
      immune responses. It is concluded that, beta-glucan can induce Th1 as well asTh2
      driven immune responses. The pathology of atopy/allergy, hypersensitivity
      pneumonitis, and toxic penumonitis might be induced by exposure to beta-glucan.
      Measurements of beta-glucan in different environments are useful for risk control
      and prevention.

PMID- 20684477
TI  - Non-malignant respiratory diseases and occupational exposure to wood dust. Part
      I. Fresh wood and mixed wood industry.
AB  - This paper reviews associations in literature between exposure to wood dust from
      fresh wood and non-malignant respiratory diseases. Criteria for inclusion are
      epidemiological studies in English language journals with an internal or external
      control group describing relationships between wood dust exposure and respiratory
      diseases or symptoms. The papers took into account smoking, and when dealing with
      lung function took age into consideration. A total of 25 papers concerning
      exposure to fresh wood and mixed wood formed the basis of this review. The
      results support an association between fresh wood dust exposure and asthma,
      asthma symptoms, coughing, bronchitis, and acute and chronic impairment of lung
      function. In addition, an association between fresh wood dust exposure and rhino
      conjunctivitis was seen across studies. Apart from plicatic acid in western red
      cedar wood, no causal agent was consistently disclosed. Type 1 allergy is not
      suspected of being a major cause of wood dust induced asthma. Concurrent exposure
      to microorganisms and terpenes probably add to the inherent risk of wood dust
      exposure in the fresh wood industry.

PMID- 20684478
TI  - Non-malignant respiratory diseases and occupational exposure to wood dust. Part
      II. Dry wood industry.
AB  - This paper reviews the literature on associations between dry wood dust exposure
      and non-malignant respiratory diseases. Criteria for inclusion are
      epidemiological studies in English language journals with an internal or external
      control group describing relationships between dry wood dust exposure and
      respiratory diseases or symptoms. Papers took into consideration smoking and when
      dealing with lung function age. A total of 37 papers forms the basis of this
      review. The results support an association between dry wood dust exposure and
      asthma, asthma symptoms, coughing, bronchitis, and acute and chronic impairment
      of lung function. In addition, an association between wood dust exposure and
      rhino-conjunctivitis is seen across the studies. Apart from plicatic acid in
      western red cedar wood, no causal agent has consistently been disclosed. Type 1
      allergy is not suspected to be a major cause of wood dust induced asthma.

PMID- 20684479
TI  - Analysis of expression and amino acid sequence of the allergen Mag 3 in two
      species of house dust mites-Dermatophagoides farinae and D. pteronyssinus (Acari:
      Astigmata: Pyroglyphidae).
AB  - In the 90's of the XX century, 2 new and important allergens of house dust mites
      mites were cloned and sequenced: Mag 1 and Mag 3. However, the second allergen
      has been identified to date only in extracts of Dermatophagoides farinae [DF ].
      In this work, we aimed to detect expression of this important allergen and for
      the first time analyze to the amino acid sequence in other species of house dust
      mite - Dermatophagoides pteronyssinus [DP ]. We were able to confirm the
      expression of allergen Mag 3 in DF and to exclude it in DP . By sequencing the
      products of DNA amplification, we revealed the nucleotide sequence encoding
      allergen Mag 3 in DF . This analysis enabled detection of 9 single base changes.
      An analysis of encoded amino acid sequence by triplets with substituted
      nucleotides revealed that 8 changes were polymorphic, and 1 was a mutation
      substituting GTG (valine) for ATG (methionine) at 236 position. However, the
      presence of amino acid sequence difference in this allergen might suggest that
      there exist other isoforms which can make difficult both diagnosis as well as
      immunotherapy in persons who produce allergic response to this allergen. The
      variants of allergen Mag 3 (group 14) are still not known beside the very good
      known allergen variants of the other main groups 1, 2, 4, 5 or 7. Thus, the
      identification and definition of allergic properties of allergen Mag 3 variants
      needs to be further investigated.

PMID- 20684480
TI  - Mosquito fauna and perspectives for integrated control of urban vector-mosquito
      populations in Southern Benin (West Africa).
AB  - This study aims at an integrated vector management (IVM) concept of implementing
      biological control agents against vector mosquito larvae as a cost-effective and
      scalable control strategy. In the first step, the mosquito species composition
      fauna of southern Benin was studied using standard entomological procedures in
      natural and man-made habitats. Altogether, 24 species belonging to 6 genera of
      mosquitoes Aedes, Anopheles, Culex, Mansonia, Uranotaenia, Ficalbia were
      recorded. Five species, Cx. thalassius, Cx. nebulosus, Cx. perfuscus, Cx.
      pocilipes and Fi. mediolineata are described the first time for Benin. The local
      mosquito species showed high susceptibility to a Bacillus sphaericus formulation
      (VectoLex(R) WDG ) in a standardized field test. A dosage of 1 g/m(2) was
      effective to achieve 100 percent mortality rate for Cx. quinquefasciatus late
      instar larvae in a sewage habitat, with a residual effect of up to 7 days. After
      more than 1 year of baseline data collection, operational larviciding with B.
      thuringiensis var. israelensis and B. sphaericus was commenced in 2006 in
      selected areas. Microbial insecticides products for larval control show great
      potential within IVM programmes and may augment control efforts against adult
      insects, such as the use of insecticide-treated bed nets or indoor wall spraying
      in many parts of Africa.

PMID- 20684481
TI  - Machine-related farm injuries in Turkey.
AB  - Traumas connected with agricultural production can result in serious injuries and
      mortality. The objective of the study was to describe the characteristics of
      agricultural machines related work injury cases admitted to the Emergency
      Department, and to asses factors related to injury severity and hospital
      admission in the Central Anatolian Region of Turkey. All the cases presented
      related to injuries caused by work with agricultural machines between January
      2006-November 2007 were included in the study. Information was collected
      concerning the demographic structures of the patients. Injury sites, injury
      types, and clinical features were recorded. Initial injury severity scores of all
      the cases were diagnosed at hospital admission. 91.9 percent of the cases were
      male. Mean age was 35.8 +- 17.0. The most common machine causing injuries was a
      tractor with 46 percent of cases, and all of these were fall traumas. 18.9
      percent of the cases was considered as slight injury, 43.2 percent as moderate,
      and 37.9 percent as severe. Two male cases resulted in fatality. Our findings
      suggest that tractors are the most dangerous agricultural machines, and falls
      from tractors as the most common injury mechanism among machine-related injuries,
      especially for young people. In the rural areas of our country, Turkey,
      agricultural machines cause serious injuries that require hospitalization.

PMID- 20684482
TI  - Effects of stress pretreatment on the dynamics of blood cholinesterase activity
      after exposure to an organophosphorus pesticide in the rat.
AB  - A single i.p. administration of 1.0 mg/kg of chlorphenvinphos (CVP), an
      organophosphorus pesticide, results in an acute stress response, evidenced by a
      marked (6-7 fold) rise in plasma corticosterone (CORT) concentration, and a
      diminished behavioural sensitivity to amphetamine (AMPH) three weeks
      postexposure. Surprisingly, in rats subjected to a single series of inescapable
      electric footshocks (60 10 msec triplets of 3.0 mA, 2 msec, square pulses during
      20 min - IF ) two weeks prior to the CVP exposure, these effects are not
      observed. It has been assumed that the reduced effectiveness of CVP might be
      related to some persisting alterations in the functional state of the cholinergic
      system. The aim of the present work was to discover whether and in what way the
      IF pretreatment affects i) the cholinesterase activity in blood, and ii) the
      dynamics of the alterations in the cholinesterase (ChE) activity following the
      CVP exposure. The experiments were performed on 3 mo. old, male Wistar rats. In
      the first experiment, the blood samples were taken from the tail vein 15, 60 and
      180 min after the IF. In the second experiment, the rats were pretreated with IF
      and 14 days later given 1.0 mg/kg of CVP i.p. Blood samples were taken 15 min, 60
      min, 180 min, 24 h, 7 days, and 14 days after the CVP exposure. In the first
      experiment no differences in the ChE activity in plasma (pChE) and erythrocytes
      (rbcChE) were found between the shocked and control rats. In the second
      experiment, however, in rats pretreated with IF the rbcChE activity of was
      reduced by CVP less and pChE activity returned to normal faster than in rats not
      pretreated with IF. The results confirm that exposure to IF, a nonchemical
      stressor, induces some long-lasting adaptive changes which render the cholinergic
      system less susceptible to the harmful action of ChE inhibitors. It has been
      hypothesized that the changes consist in an increase of the antioxidant potential
      in blood and possibly other tissues.

PMID- 20684483
TI  - Is concentration and motility of male gametes related to DNA damage measured by
      comet assay?
AB  - Approximately 8 percent of couples in the World have problem with offspring
      production. Male infertility, which is the reason of the half of reproduction
      failures, is connected with diminished sperm production and deterioration of its
      quality. One important factor which affects fertility is the appearance of DNA
      damage in germ cells leading to enhanced frequency of mutations. This study aimed
      to compare the frequency of DNA damage in human spermatozoa in samples of
      different sperm concentration and motility. The anonymous sperm sample donors
      were men aged from 20-44 years, couples of pregnant females. Sperm concentration,
      motility and DNA damage measured by Comet assay were estimated. The following
      parameters were chosen for analysis of DNA damage: percent of DNA in comet head,
      comet tail length, tail moment. There were no differences in the mean DNA damage
      in male gametes between different age groups of donors, nor between samples of
      different sperm motility. The correlation between low sperm concentration in
      ejaculate and enhanced level of DNA damage was observed. The highest DNA damage
      was noted in samples with low sperm concentration. In gametes from this group,
      the lowest percent of DNA in comet head, the highest mean tail length, and the
      highest tail moment were observed.

PMID- 20684484
TI  - Distribution of trichothecene and zearalenone producing Fusarium species in grain
      of different cereal species and cultivars grown under organic farming conditions
      in Lithuania.
AB  - Fusarium infection level, DNA quantity of the Fusarium poae, F. sporotrichioides,
      F. langsethiae, F. culmorum, F. graminearum and F. equiseti as well as
      deoxynivalenol (DON), zearalenone (ZEN ) and T-2 toxin (T-2) content were
      investigated in grain from cultivars of different cereal species grown on organic
      farming sites during 2005-2006. The Fusarium infection level was examined by agar
      plating of single grains, Fusarium spp. DNA content was determined by real-time
      PCR and the mycotoxins were analyzed by ELISA. Almost all cereal grain samples
      grown under organic conditions were infected by Fusarium spp. The grains of
      winter cereals were less infected with Fusarium compared with those of spring
      cereals. The presence of F. culmorum, F. equiseti, F. sporotrichioides, F. poae,
      F. langsethiae in cereal grain depended on the environmental conditions during
      the experimental years. Higher Fusarium species diversity was found in 2005 when
      the conditions were more favourable for Fusarium infection in cereal grain,
      whereas F. poae and F. langsethiae were prevalent in cereal grain in 2006. F.
      langsethiae, identified in Lithuania for the first time, was more frequent in
      spring cereals than in winter cereals. Almost all grain samples were found to be
      contaminated with DON, ZEN, T-2 at low concentrations; however, it is known that
      the action of toxins at low concentrations is slow, the adverse effects are
      evidenced only after some time and in different forms, which poses a serious risk
      to human and animal health.

PMID- 20684485
TI  - Influence of meteorological parameters in hourly patterns of grass (Poaceae)
      pollen concentrations.
AB  - Hourly grass pollen concentrations were recorded over a 10-year study period at
      an aerobiological station of Badajoz (SW Spain). The record was carried out by
      means of a Burkard spore trap. Meteorological data were used to find correlation
      with the hourly patterns in the months of principal concentration. The observed
      variations were found to be due to independent contributions of patterns
      corresponding to different groups of species within the family of grasses. Three
      pollen concentrations peaks were recognized. Peak A, at around 10:00 h, of great
      importance in April and May, although maintained until July; peak B, at around
      15:00 h, important in April, May and June; and peak C, towards the end of the
      day, dominant in July. Differences with respect to the pollen sources responsible
      for these peaks are suggested by the influence of the meteorological parameters
      before and during flowering. The results are directly applicable to the
      epidemiology of allergies in the zone, since the thresholds of grass pollen
      concentrations capable of triggering allergic processes shift from the central
      hours of the day in April and May to the night hours in July. Also, considering
      the observed patterns of hourly grass pollen concentrations as the result of
      combining different models could explain the annual and geographical variations
      found at other locations.

PMID- 20684486
TI  - Contents of microscopic fungi in dusts coming from cereal analysis laboratories.
AB  - Microscopic fungi - components of bioaerosol found in the workplace environment
      of individuals employed in the agricultural sector - constitute a considerable
      hazard for their health. This study includes quantitative and qualitative
      analyses of mycobionta contained in 20 samples of dusts collected from
      laboratories conducting analyses of cereals. A total of 27 species of viable
      microscopic fungi were isolated. The most frequently isolated genera Penicillium
      and Aspergillus, accounting for 27 percent and 26 percent of analyzed isolates.
      The content of fungal biomass was determined quantitatively using a fungal
      marker, ergosterol (ERG). Concentrations of this metabolite for all samples
      ranged from 0.48 mg/kg-212.36 mg/kg. Based on the analyses, it may be stated that
      the concentration of microfungi in settled dust from laboratories conducting
      analyses of cereals was varied, and in several cases markedly exceeded admissible
      concentration levels.

PMID- 20684487
TI  - Psychosocial factors and health-related behavior among students from South-East
      Poland.
AB  - The aim of this study was to determine the meaning of selected social-demographic
      factors, such as: gender, place of resident, education, level of knowledge about
      health and life orientation in modifying the behaviours related to health among
      university students.The study was conducted among 521 students of two major
      universities of the South-Eastern Region of Poland. The survey was conducted by
      means of a diagnostic survey with the use of the Inventory of Health-Related
      Behaviuor (Zygfryd Juczynski?s IZ ), A. Antonovsky?s Sense of Coherence
      Questionnaire SOC-29 and the original questionnaire, including socio-demographic
      variable, as well as a test of statements considering the assessment of the level
      of knowledge about health. Methods of descriptive statistics, such as: mean,
      standard deviation, median, upper and lower quartile, and highest and lowest
      value, methods of analysis of variance, the chi-square test, correlation and
      linear regression and Spearman?s rank correlation coefficient, one-way analysis
      of variance, Pearson product-moment correlation coefficient, and backward
      stepwise regression were used for statistical analysis. The study showed that
      almost a half of respondents (48.9 percent) were characterized by a low intensity
      of pro-health behaviour, and among 38.4 percent it was on an average level.
      Gender was a factor that differentiated the intensity of health-related behaviour
      - women indicated a higher level of these behaviours. Almost half of the studied
      group (48.6 percent) was characterized by a low level of knowledge about health.
      The major meaning among studied factors influencing health-related behaviour in
      the regression model had the level of sense of coherence, gender and material
      status.

PMID- 20684488
TI  - Glass surface as potential in vitro substratum for Candida famata biofilm.
AB  - The biofilm of Candida spp. is a three-dimensional structure consisting of a
      dense network of yeasts, blastospores and/or filamentous elements (hyphae or
      pseudohyphae). All species of Candida are able to form biofilm. The aim of this
      paper is to present data concerning biofilm formation under static conditions by
      oropharyngeal isolates of C. famata on a glass surface using non-invasive
      confocal scanning laser microscopy (CSLM ). The changes in five parameters
      calculated using the CSLM technique, i.e. areal porosity (percent), fractal
      dimension (D), length of edge line (mm/mm2), length of skeleton line (mm/mm(2)),
      number of cell clusters/mm(2), describing the biofilm structure of C. famata
      isolates after 1 h incubation (the adhesion step), 24 h incubation (biofilm
      formation) and 72 h incubation (mature biofilm), indicate the morphological
      reorganization of biofilm during maturation. The thickness of biofilm C. famata
      isolates after 72 h incubation ranged from 35.2 to 81.2 micrometer.

PMID- 20684489
TI  - Genetic aspect of venom allergy: association with HLA class I and class II
      antigens.
AB  - Stings from bees and wasps can cause systemic allergic reactions in sensitized
      patients. However, the mystery of why some cases develop allergic reactions while
      others do not, remains poorly understood. We investigated whether particular
      human leukocyte antigen (HLA) class I and class II genes contribute to the
      development of venom allergy. A total of 21 bee and/or wasp venom sensitive
      patients who had life-threatening allergic symptoms after a sting, and positive
      diagnostic tests (Group 1), were included in the study. Thiry-seven healthy
      subjects without venom allergy (Group 2) were selected as the control group. HLA 
      class I (A-C) and class II (DR, DQ, DP ) typing was performed by PCR-based
      techniques. HLA -B*18 and HLA -Cw*07 alleles was found more frequently in Group1
      than in Group 2 (14.3 percent vs 2.7 percent, p=0.026, and 31 percent vs 14.9
      percent, p=0.036, respectively). Furthermore, HLA -A*01 allele frequency had a
      trend to be higher in Group 1 than in Group 2 (14.3 percent vs 4.1 percent,
      p=0.055). However, the frequencies of HLA -A*03 and HLA -Cw*03 alleles were
      increased in Group 2 compared to Group 1 (20.3 percent vs 7.1 percent, p=0.049
      and 10.8 percent vs 0 percent, p=0.024, respectively). Among HLA -class II
      genotypes, HLA -DQB1*03 allele was significantly increased in Group 2 (60.9
      percent vs 38.1 percent, p=0.018), while a higher frequency of HLA -DR B1*03 and
      HLA -DR B1*14 alleles showed a tendency statistically significant in Group 1 (9.5
      percent vs 1.4 percent, p=0.057 and 11.9 percent vs 2.7 percent, p=0.058,
      respectively). HLA -B*18 and HLA -Cw*07 alleles may probably be associated with
      susceptibility to venom allergy, whereas HLA -A*03, HLA -Cw*03 and HLA -DQB1*03
      seem to be protective markers in a small Turkish population.

PMID- 20684490
TI  - The occurrence of Toxoplasma gondii infection in people and animals from rural
      environment of Lublin region - estimate of potential role of water as a source of
      infection.
AB  - A total of 254 humans and 489 domestic animals living on farms in the Lublin
      province (eastern Poland) were examined for the presence of antibodies against
      Toxoplasma gondii using, respectively, the ELFA and direct agglutination tests.
      In parallel, 182 samples of potable water, mostly from shallow household wells,
      were taken on farms and examined for the presence of T. gondii by microscopy and
      PCR. The frequency of seropositive reactions in farm inhabitants (66.9 percent)
      was significantly greater (p < 0.01) compared to the reference group of 39
      healthy urban dwellers (41.0 percent). A highly significant positive correlation
      was found between the age of examined farm inhabitants and the rate of positive
      reactions with Toxoplasma antigen (p < 0.0001). Among domestic animals, the
      greatest frequency of seropositive reactions to T. gondii occurred in cats (75.0
      percent) and dogs (53.6 percent), less frequent in cattle (33.8 percent) and hens
      (33.5 percent) and the least frequent in pigs (17.9 percent) and ducks (21.2
      percent). The presence of T. gondii was found in potable water samples taken from
      water intakes on farms: in 12.6 percent of samples by microscopy, and in 22.5
      percent of samples by PCR. Among 19 water samples taken from bathing places on
      the territory of the Lublin province, 2 samples positive for T. gondii (10.5
      percent) were found by microscopic examination and confirmed by PCR . The
      presence of live parasites in water samples was demonstrated by the isolation of
      Toxoplasma gondii strains in mice. By use of RFLP -PCR it was found that the
      majority of isolated Toxoplasma strains (78.0 percent) belonged to clonal type I
      which is most virulent for humans and animals. Although no statistically
      significant relationship between the presence of T. gondii in water and
      occurrence of seropositive reactions in farm inhabitants and/or domestic animals
      could be found, the above-mentioned data suggest a potential role of potable
      water in the spread of toxoplasmosis in the rural environment.

PMID- 20684491
TI  - Prevalence of cigarette smoking among adult population in eastern Poland.
AB  - Cigarette smoking is the strongest modifiable factor, which shortens the life
      span and deteriorates the quality of life. It increases the risk of development
      of cancer, cardiovascular and respiratory system diseases. The objective of the
      study was evaluation of the prevalence of cigarette smoking among the adult
      population of the Lublin Region, and investigation of the relationship between
      nicotinism and respondents? place of residence, and other selected socio-economic
      factors. Data concerning the cigarette smoking habit was obtained from 3,993
      people - 2,447 females and 1,546 males; 23.0 percent of respondents in the study
      were smokers - 35.6 percent of males and 15.1 percent of females. The percentage
      of male smokers was similar in rural and urban areas. Urban females were smokers
      more often than those living in rural areas. A decrease was noted in the
      difference which has been observed to-date between the percentage of urban and
      rural female smokers. The highest percentage of smokers occurred among the
      population aged 41-50, while the lowest - among the youngest and the oldest
      respondents. The percentage of smoking farmers was lower than that of respondents
      performing non-agricultural occupations, also among rural inhabitants. Those who
      were occupationally active were smokers more frequently than those not engaged in
      occupational activity. The lowest percentage of smokers was noted among
      respondents who had the highest education level, while the highest percentage was
      observed among those who had vocational education.

PMID- 20684492
TI  - Pollen spectrum and risk of pollen allergy in central Spain.
AB  - The present work analyses the airborne pollen dynamic of the atmosphere of Toledo
      (central Spain), a World Heritage Site and an important tourist city receiving
      over 2 millions of visitors every year. The airborne pollen spectrum, the annual
      dynamics of the most important taxa, the influence of meteorological variables
      and the risk of suffering pollen allergy are analysed. Results of the present
      work are compared to those obtained by similar studies in nearby regions. The
      average annual Pollen Index is 44,632 grains, where 70-90 percent is recorded
      during February-May. The pollen calendar includes 29 pollen types, in order of
      importance; Cupressaceae (23.3 percent of the total amount of pollen grains),
      Quercus (21.2 percent), and Poaceae and Olea (11.5 and 11.2 percent,
      respectively), are the main pollen producer taxa. From an allergological
      viewpoint, Toledo is a high-risk locality for the residents and tourist who visit
      the area, with a great number of days exceeding the allergy thresholds proposed
      by the Spanish Aerobiological Network (REA). The types triggering most allergic
      processes in Toledo citizens and tourists are Cupressaceae, Platanus, Olea,
      Poaceae, Urticaceae and Chenopodiaceae-Amaranthaceae. Allergic risk increases in
      3 main periods: winter (January-March), with the main presence of the
      Cupressaceae type; spring, characterized by Poaceae, Olea, Platanus and
      Urticaceae pollen types; and, finally, late summer (August-September),
      characterized by Chenopodiaceae- Amaranthaceae pollen type, which are the main
      cause of allergies during these months.

PMID- 20684493
TI  - Valproic acid transfer across human placental cotyledon during dual perfusion in
      vitro.
AB  - Valproic acid (VPA ) is a well-known antiepileptic drug with a significant
      teratogenic effect when administered during pregnancy. To investigate the
      transplacental transport of VPA, we used an in vitro experiment of dual perfusion
      of a human placental cotyledon. Eighteen normal placentas at term were
      investigated; ten were treated with a therapeutic dose of VPA (initial level at
      maternal circulation 75 microgram/ml), while the remaining eight were supplied
      with toxic VPA doses (initial level at maternal circulation 225 microgram/ml).
      VPA concentrations in fetal compartment were lower than those in the maternal
      compartment at all timepoints with both doses applied. The maternal and foetal
      VPA concentrations were stable at 60 min and 120 min for the therapeutic dose of
      VPA (transfer percentages from the maternal to the fetal circulation were 22.7 +-
      9.1 percent and 22.7 +- 7.1 percent, respectively). Interestingly, a significant
      decrease of VPA level in the maternal perfusate was observed after 120 min due to
      the slightly higher transfer of the drug to the foetal compartment. In
      conclusion, our data confirmed an easy and rapid transfer of VPA accross the
      placental barrier. Since the incidence of congenital malformations in infants
      correlates positively with VPA concentrations in maternal serum, monitoring of
      VPA should be mandatory due to possible harmful effects on the foetus.

PMID- 20684494
TI  - Differences in breast cancer incidence and stage distribution between urban and
      rural female population in Podlaskie Voivodship, Poland in years 2001-2002.
AB  - The aim of the study was to evaluate differences in breast cancer incidence and
      stage of disease between the urban and rural female population in Podlaskie
      Voivodship in 2001-2002, before the introduction of the Population Screening
      Programme in 2006. Analysis was based on 696 breast cancer cases diagnosed in
      years 2001-2002 and registered in the CR in Bialystok (Voivodship Cancer
      Registry). An average annual number of incidence, as well as crude and
      standardised incidence rates, were calculated. Age-specific incidence rates for 5
      year age groups were also calculated and grouped as follows: < 50, 50-69, > =70
      years old. Incidence differences related to place of residence: urban or rural,
      were presented with the use of u/r (urban/rural) ratio. In order to evaluate the
      stage of disease, a simplified classification recommended by ENCR (European
      Network of Cancer Registries) for population registries (localised, regional,
      metastatic) was applied. The breast cancer incidence rate in the urban population
      was higher than in rural areas with u/r ratio amounting to 1.4. The highest
      incidence and largely marked differences between urban and rural areas were among
      women aged 50-69 years with the u/r ratio amounting to 1.8. Overall, the
      proportion of stage localised in Podlaskie Voivodship was 33.1 percent and
      differed between urban and rural areas. The proportion of localised cancer was
      higher in urban areas, but patients were younger when compared to those living in
      rural areas. Knowledge of differences in incidence and breast cancer stage in
      urban and rural women investigated in this research, together with other
      epidemiological indicators, should be used for monitoring the Population
      Screening Programmes in these populations.

PMID- 20684495
TI  - Low atmospheric pressure and humidity are related with more frequent pulmonary
      embolism episodes in male patients.
AB  - Pulmonary embolism is a frequent condition, related with high mortality.
      Frequency of pulmonary embolism episodes has been related with several
      meteorological factors. The aim of the study was to analyze the influence of
      meteorological factors on the occurrence of pulmonary embolism in male and female
      patients. Medical data of patients hospitalized at our institution in 2007-2008
      was analyzed. Study group included 400 patients with pulmonary embolism, living
      in the region located at an average level of about 200 m above sea level, with
      climate of a transitional character between maritime and continental climates. No
      significant differences in seasonal distribution of pulmonary embolism episodes
      were observed. A significant inverse correlation of the number of pulmonary
      embolism cases and atmospheric pressure, as well as air humidity, was identified
      in male patients. No significant correlations of temperature, wind velocity,
      precipitation and number of PE cases were observed. The influence of
      meteorological factors on the occurrence of pulmonary embolism in males is a new
      finding. A prospective study is warranted to further analyze this result.

PMID- 20684496
TI  - Human dirofilariosis in the Slovak Republic - a case report.
AB  - The spread of dirofilariosis, as a newly emerging zoonosis, due to global changes
      has been documented in several Central European countries. In Slovakia, the first
      autochthonous case of dirofilariosis was recorded in dogs in 2005. The first case
      of human subcutaneous dirofilariosis caused by Dirofilaria repens was diagnosed
      in a 60- year-old patient from an area of western Slovakia. We report another
      case of dirofilariosis in a 37-year-old woman living in the same area of south
      western Slovakia. The infection manifested as a painful, inflamed nodule on the
      back of the left hand, containing an adult parasite. Morphological analysis
      aroused suspicion of the presence of a filarial worm belonging to the genus
      Dirofilaria. Subsequent PCR analysis of the DNA identified the parasite as
      Dirofilaria repens. After removal of the parasite, the subcutaneous nodule
      completely resolved and the patient was successfully cured.

PMID- 20684497
TI  - First case of human granulocytic anaplasmosis from Slovakia.
AB  - In order to evaluate the potential risks of human granulocytic anaplasmosis in
      Slovakia, blood and serum samples of hunters and foresters from the northern
      parth of Slovakia were tested. We present the first case of HGA from Slovakia
      confirmed by nested PCR amplification of the 16S rRNA gene fragment of A.
      phagocytophilum.

PMID- 20684498
TI  - Electric-field-induced local layer structure in plasticized PVC actuator.
AB  - In order to investigate the molecular vibrations and structure variations of PVC
      gels with applied electric fields, a mechanical measurement (combined tensile and
      shear test) was proposed, and the Fourier transform infrared (FT-IR) spectrometry
      and in situ Raman spectroscopy were conducted to clarify the mechanism of
      electric-field-induced local layer structure in PVC gel and its relationship to
      gel creeping deformation. As a result, the electric-field-induced local layer
      structure and the migration of the solvent-rich phase in PVC gels were clarified.
      The layer of PVC gel clinging to the anode is softer than that near the cathode.
      The peaks of FT-IR spectra were shifted and changed in the gel surface on the
      anode and cathode. Using the in situ Raman spectroscopy, it is found that the
      intensity of the whole Raman spectra was reduced from the cathode to the anode,
      and the elastic modulus of the gel on the anode was smaller than that on the
      cathode. All of the results indicated that the electric field induced the local
      layer structure and caused the asymmetric actuation behavior in PVC gel
      actuators.

PMID- 20684499
TI  - Viscosity-dependent dynamics of CO rebinding to microperoxidase-8 in
      glycerol/water solution.
AB  - Rebinding kinetics of CO to microperoxidase-8 (Mp), an excellent model system for
      the active site of heme proteins such as myoglobin and hemoglobin, was measured
      after photolysis of MpCO in solutions with various viscosities and temperatures,
      using femtosecond vibrational spectroscopy. Whereas the geminate rebinding of CO
      to Mp in water is negligible, significant fractions of CO rebind nonexponentially
      within 1 ns at room temperature in a glycerol/water solution. The geminate yield
      of the CO rebinding increases and its rate accelerates as the viscosity of the
      solution increases either by increasing glycerol content in glycerol/water
      mixtures at 294 K or by decreasing temperature of the solution from 323 to 283 K.
      The nonexponential rebinding kinetics can be described by the theory of a
      diffusion-controlled reaction and the data are well reproduced by the pair
      survival probability function in the absence of any interaction potential between
      the pair. The rebinding kinetics was also successfully described by the SRC
      model, a distributed linear coupling model for the CO rebinding.

PMID- 20684500
TI  - Electrochemical behavior of electropolymerized and chemically synthesized
      hyperbranched polythiophenes.
AB  - Hyperbranched polythiophenes were synthesized by potentiodynamic
      electropolymerization of 2,2';3',2''-terthiophene and 5'-(2-thienyl)-2,2';3',2''
      terthiophene. The molecular architecture, i.e., the extent of branching of the
      resulting polymers, could be adjusted by varying the switching potentials. We
      compare these systems to hyperbranched polythiophenes which we obtained via a
      simple one-pot synthesis route based on FeCl(3) oxidative polymerization of the
      monomers. Interestingly, we find that the properties of the electropolymerized
      materials obtained with high switching potentials are comparable to those of the
      chemically synthesized polythiophenes. A detailed optical and electrochemical
      characterization of these systems is performed showing the high potential of this
      material class for optoelectronic applications. Cyclic voltammetry coupled with
      in situ conductance measurements further reveal reversible doping upon oxidation
      (p-doping) and reduction (n-doping) and comparable values for the conductance for
      the chemically and electrochemically synthesized materials.

PMID- 20684501
TI  - Photophysics and photodeprotection reactions of p-methoxyphenacyl phototriggers:
      an ultrafast and nanosecond time-resolved spectroscopic and density functional
      theory study.
AB  - Time-resolved spectroscopic experiments were performed to investigate the
      kinetics and mechanisms of the photodeprotection reactions for p-methoxyphenacyl
      (pMP) compounds, p-methoxyphenacyl diethyl phosphate (MPEP) and diphenyl
      phosphate (MPPP). The experimental results reveal that compared to the previous
      reports for the counterpart p-hydroxyphenacyl (pHP) phosphates, the (3)npi*/pipi*
      mixed character triplet of pMP acts as a reactive precursor that leads to the
      subsequent solvent and leaving group dependent chemical reactions and further
      affects the formation of photoproducts. The MPPP triplet in H(2)O/CH(3)CN and in
      fluorinated alcohols shows a rapid heterolytic cleavage (tau approximately 5.4
      ns) that results in deprotection and formation of a solvolytic rearrangement
      product, whereas the MPPP triplet in CH(3)CN and the MPEP triplet in CH(3)CN and
      H(2)O/CH(3)CN and fluorinated alcohols decay on a much longer time scale (tau
      approximately 100 ns) with little observation of the rearrangement product. The
      density functional theory (DFT) calculations reveal a substantial solvation
      effect that is connected with the methoxy versus hydroxyl substitution in
      accounting for the different deprotection reactivity of pMP and pHP compounds.
      The results reported here provide new insight in elucidating the solvent and
      leaving group dependent dual reactivity of pMP compounds on the formation of the
      rearrangement versus reductive photoproduct.

PMID- 20684502
TI  - Nucleophilic cycloaromatization of ynamide-terminated enediynes.
AB  - Introduction of a nitrogen atom at one of the acetylenic termini of 10-, 11-, 12
      , and 13-membered benzannulated cyclic enediynes results in a complete
      suppression of the conventional radical Bergman reaction in favor of a polar
      cycloaromatization. The latter reaction is catalyzed by acids and proceeds via
      initial protonation of an ynamide fragment. The resulting ketenimmonium cation
      then cyclizes to produce naphthyl cation, which rapidly reacts with nucleophiles
      or undergoes Friedel-Crafts addition to aromatic compounds. In alcohols, addition
      of the nucleophilic solvent across the activated triple bond competes with the
      cyclization reaction. The ratio of cyclized to solvolysis products decreases with
      the increase in ring size.

PMID- 20684503
TI  - Oxidative potential of logwood and pellet burning particles assessed by a novel
      profluorescent nitroxide probe.
AB  - This study reports the potential toxicological impact of particles produced
      during biomass combustion by an automatic pellet boiler and a traditional logwood
      stove under various combustion conditions using a novel profluorescent nitroxide
      probe, BPEAnit. This probe is weakly fluorescent but yields strong fluorescence
      emission upon radical trapping or redox activity. Samples were collected by
      bubbling aerosol through an impinger containing BPEAnit solution, followed by
      fluorescence measurement. The fluorescence of BPEAnit was measured for particles
      produced during various combustion phases: at the beginning of burning (cold
      start), stable combustion after refilling with the fuel (warm start), and poor
      burning conditions. For particles produced by the logwood stove under cold-start
      conditions, significantly higher amounts of reactive species per unit of
      particulate mass were observed compared to emissions produced during a warm
      start. In addition, sampling of logwood burning emissions after passing through a
      thermodenuder at 250 degrees C resulted in an 80-100% reduction of the
      fluorescence signal of the BPEAnit probe, indicating that the majority of
      reactive species were semivolatile. Moreover, the amount of reactive species
      showed a strong correlation with the amount of particulate organic material. This
      indicates the importance of semivolatile organics in particle-related toxicity.
      Particle emissions from the pellet boiler, although of similar mass
      concentration, were not observed to lead to an increase in fluorescence signal
      during any of the combustion phases.

PMID- 20684504
TI  - Origin of rare and highly efficient phosphorescent and electroluminescent
      iridium(III) complexes based on C--N=N ligands, a theoretical explanation.
AB  - The origin of the rare and highly strong phosphorescent (PL) and
      electroluminescent (EL) Ir(III) complexes with C--N=N ligand, tris[3,6
      bis(phenyl)pyridazinato-N(1),C(2)]iridium (Ir(BPPya)(3)) (1), tris[1,4
      bis(phenyl)phthalazine]iridium (Ir(BPPa)(3)) (2), and tris[1-(2,6
      dimethylphenoxy)-4-(4-chlorophenyl)phthalazine]iridium ((Ir(MPCPPZ)(3)) (3) are
      investigated theoretically. By changing the conjugation length of the C--N=N
      ligand from BPPya to BPPa, one can tune the emission color from green in 1 to
      saturated red in 2. The addition of sterically bulky phenolic substituents in 3
      exhibits the highest external quantum efficiency of 20.2% ph el(-1) and
      luminescence efficiency of 18.4 cd A(-1). Density functional theory (DFT) and
      time-dependent DFT (TDDFT) methods are used to rationalize these properties. The
      more promising PL and EL properties of 3 result from the bulky phenolic group,
      which acts as a pendant at the periphery of the emitting core and protects the
      emitting core from the hazardous intermolecular interaction of emitters and
      reduces luminescence quenching.

PMID- 20684505
TI  - Silver- and gold-mediated intramolecular cyclization to substituted tetracyclic
      isoquinolizinium hexafluorostilbates.
AB  - A convenient route for the synthesis of various charged tetracyclic
      isoquinolizinium hexafluorostilbates was developed using AgSbF(6)/AuCl(PPh(3))
      for the intramolecular addition of amine to alkyne. The described process is
      tolerant of a variety of functional groups and broadens the diversity of
      substrates with the use of 8-substituted tetracyclic isoquinolizinium salts.

PMID- 20684506
TI  - From pore scale to column scale dispersion in capillary silica monoliths.
AB  - We study time and length scales of eddy dispersion in 100 mum i.d. capillary
      silica monoliths. First, the monolith's macropore morphology was visualized over
      complete column cross sections by confocal laser scanning microscopy, revealing a
      wall region with large voids (with a lateral dimension of up to approximately 15
      mum) and a homogeneous core region. A bulk segment from the core region was then
      physically reconstructed to receive a 60 x 12 x 12 mum matrix consisting of
      approximately 3 x 10(8) cubic voxels of 30 nm edge length for direct numerical
      simulations of fluid flow by the lattice-Boltzmann method and convective
      diffusive mass transport by a random-walk particle-tracking technique on a high
      performance computing platform. Pore-scale dispersion was analyzed in detail
      using the generalized Giddings equation. Eddy dispersion contributions
      originating in the bulk macropore heterogeneity were quantified and correlated
      with structural features of the monolith. To complement the simulation results,
      column scale dispersion was investigated by analysis of chromatographic plate
      heights. We found a much smaller bulk dispersion than generally assumed for
      silica monoliths (plate heights of approximately 2 mum over a wide velocity
      range), promising excellent separation efficiency also at high flow velocities (
      approximately 1 cm/s). This potential is not realized by the capillary monolith
      in chromatographic practice because of the wall defect.

PMID- 20684507
TI  - Synthesis of 2,3-dihydroquinazolin-4(1H)-ones by three-component coupling of
      isatoic anhydride, amines, and aldehydes catalyzed by magnetic Fe(3)O(4)
      nanoparticles in water.
AB  - A simple and efficient protocol for one-pot three-component coupling of isatoic
      anhydride, amines, and aldehydes in water using magnetically recoverable
      Fe(3)O(4) nanoparticles is reported. This methodology results in the synthesis of
      a variety of 2,3-dihydroquinazolin-4(1H)-ones in high yields. The catalyst can be
      recovered and recycled without a significant loss in the catalytic activity.

PMID- 20684508
TI  - Quantum corral resonance widths: lossy scattering as acoustics.
AB  - We present an approach to predicting extrinsic electron resonance widths within
      quantum corral nanostructures based on analogies with acoustics. Established
      quantum mechanical methods for calculating resonance widths, such as multiple
      scattering theory, build up the scattering atom by atom, ignoring the structure
      formed by the atoms, such as walls or enclosures. Conversely, particle-in-a-box
      models, assuming continuous walls, have long been successful in predicting
      quantum corral energy levels, but not resonance widths. In acoustics, partial
      reflection from walls and various enclosures has long been incorporated for
      determining reverberation times. Pursuing an exact analogy between the local
      density of states of a quantum corral and the acoustic impedance of a concert
      hall, we show electron lifetimes in nanoscopic structures of arbitrary convex
      shape are well accounted for by the Sabine formula for acoustic reverberation
      times. This provides a particularly compact and intuitive prescription for
      extrinsic finite lifetimes in a particle-in-a-box with leaky walls, including
      quantum corral atomic walls, given single particle scattering properties.

PMID- 20684509
TI  - A fluorescence perspective on the differential interaction of riboflavin and
      flavin adenine dinucleotide with cucurbit[7]uril.
AB  - The interaction of the macrocyclic host, cucurbit[7]uril (CB7), with riboflavin
      (RF) and its derivative, flavin adenine dinucleotide (FAD), has been investigated
      using absorption and steady-state and time-resolved fluorescence measurements.
      Interestingly, in the presence of CB7, the fluorescence intensity of RF is
      quenched, whereas the fluorescence intensity of FAD is enhanced. It is proposed
      that the fluorescence quenching of RF results from the tautomerization of its
      isoalloxazine moiety from the lactam to the lactim forms, upon binding to CB7.
      Such a tautomerization can be brought about since the two lactim forms have
      higher dipole moments than the lactam form of RF, and thus experience much
      stronger dipole-dipole interactions (and hence greater binding affinities) with
      CB7 in the former cases than in the latter. This tautomerization in the presence
      of CB7 leads to a significant reduction in the observed radiative decay rate and
      hence a reduction in the fluorescence intensity of RF. Binding of CB7 with RF is
      confirmed by an increase in the rotational correlation time of RF in the presence
      of CB7. Geometry optimization studies indicate the formation of an exclusion
      complex between CB7 and RF, possibly stabilized by H-bonding interactions, as
      also suggested by the characteristic red shift in the absorption spectra of the
      CB7-RF system. In the case of FAD, both the isoalloxazine ring and the adenine
      moiety can interact with the CB7 host. In aqueous solutions, a good fraction of
      FAD molecules exists in a "closed" conformation with the adenine and
      isoalloxazine rings stacked together, thus leading to very efficient fluorescence
      quenching due to the ultrafast intramolecular electron transfer from adenine to
      the isoalloxazine moiety. Binding of the adenine and/or the isoalloxazine moiety
      of FAD with CB7 inhibits the stacking interaction and changes the "closed"
      conformation to the "open" conformation, wherein the adenine and isoalloxazine
      moieties are widely separated, thus prohibiting the electron transfer process.
      This reduces the inherent fluorescence quenching of FAD molecule and results in
      the observed fluorescence enhancement. As observed for RF, the interaction of CB7
      with the isoalloxazine ring of FAD should cause fluorescence quenching due to the
      lactam to lactim tautomerization process. However, in the interplay between the
      above two opposing effects, the fluorescence enhancement due to the modulation in
      the conformational dynamics of FAD by the CB7 host predominates. The
      conformational change is in fact supported by the observation of a long lifetime
      component in the fluorescence decay of FAD in the presence of CB7. Moreover, at
      acidic pH, when FAD is already present mainly in the "open" form, the
      conformational dynamics no longer plays any major role and the fluorescence of
      FAD is quenched by CB7, as expected, due to the tautomerization at the
      isoalloxazine moiety.

PMID- 20684510
TI  - Identification of a regulatory segment of poly(ADP-ribose) glycohydrolase.
AB  - Coordinate regulation of PARP-1 and -2 and PARG is required for cellular
      responses to genotoxic stress. While PARP-1 and -2 are regulated by DNA breaks
      and covalent modifications, mechanisms of PARG regulation are poorly understood.
      We report here discovery of a PARG regulatory segment far removed linearly from
      residues involved in catalysis. Expression and analysis of human PARG segments
      identified a minimal catalytically active C-terminal PARG (hPARG59) containing a
      16-residue N-terminal mitochondrial targeting sequence (MTS). Deletion analysis
      and site-directed mutagenesis revealed that the MTS, specifically hydrophobic
      residues L473 and L474, was required for PARG activity. This region of PARG was
      termed the "regulatory segment/MTS" (REG/MTS). The overall alpha-helical
      composition of hPARG59, determined by circular dichroism (CD), was unaffected by
      mutation of the REG/MTS leucine residues, suggesting that activity loss was not
      due to incorrect protein folding. REG/MTS was predicted to be in a loop
      conformation because the CD spectra of mutant Delta1-16 lacking the REG/MTS
      showed a higher alpha-helical content than hPARG59, indicating a secondary
      structure other than alpha-helix for this segment. Deletion of the REG/MTS from
      full-length hPARG111 also resulted in a complete loss of activity, indicating
      that all PARG isoforms are subject to regulation at this site. The presence of
      the REG/MTS raises the possibility that PARG activity is regulated by
      interactions of PARP-1 and -2 and other proteins at this site, raises interesting
      questions concerning mitochondrial PARG because MTS residues are often removed
      after transport, and offers a potentially novel site for drug targeting of PARG.

PMID- 20684511
TI  - Three p-tert-butylthiacalix[4]arene-supported cobalt compounds obtained in one
      pot involving in situ formation of N6H2 ligand.
AB  - Three p-tert-butylthiacalix[4]arene (H(4)TC4A)-supported Co(II) compounds,
      [Co(4)(TC4A)(N(3))(4)(N(6)H(2))(CH(3)OH)](CH(3)OH)(2) (1),
      [Co(8)(TC4A)(2)(N(3))(2)(N(6)H(2))(2)(CH(3)COO)(4)(CH(3)OH)(4)](OH)(2)(CH(3)OH)(4
      (2), and [Co(10)(TC4A)(4)(N(3))(4)](CH(3)OH)(4) (3), have been solvothermally
      obtained in one pot and structurally characterized by single-crystal X-ray
      diffraction analyses, powder XRD, and IR spectroscopy. This work presents the
      first one-dimensional (1) cobalt cluster for the calixarene complexes and another
      two octanuclear (2) or decanuclear (3) cobalt clusters. In the structures of
      compounds 1 and 2, a novel N(6)H(2) ligand formed by the in situ (2 + 3)
      cycloaddition of two azides was observed. Density functional theory (DFT)
      calculations give the heat of formation (2N(3)(-) + 2H(+) --> N(6)H(2)) and
      decomposition energy (N(6)H(2) --> 3N(2) + H(2)) of 677.47 and 124.85 kcal/mol,
      respectively. Furthermore, an intergradation was determined at the B3LYP/6
      311++g(d,p) level for the formation of the N(6)H(2) ligand. In addition, one TC4A
      ligand of a sandwich unit adopts a cone conformation, while the other adopts a
      pinched cone conformation in 3. The magnetic properties of these three compounds
      were influenced mainly by the orbital contributions of the distorted octahedral
      Co(II) ions.

PMID- 20684512
TI  - Thermal stabilization of DMPC/DHPC bicelles by addition of cholesterol sulfate.
AB  - Doping DMPC/DHPC bicelles with cholesterol sulfate broadens the temperature range
      over which stable alignment occurs, forming an aligned phase at lower
      temperatures even with high lipid concentrations. Cholesterol sulfate appears to
      combine the advantages of cholesterol with those of charged amphiphiles,
      stabilizing the aligned phase and preventing precipitation. This allows NMR data
      for RDC and CSA protein structure constraints to be acquired at or below room
      temperature, an obvious advantage for solid-state and solution studies of heat
      sensitive proteins.

PMID- 20684513
TI  - Orthogonal photocleavage of a monochromophoric linker.
AB  - The 4-acetyl-2-nitrobenzyl moiety, substituted in both benzylic and phenacyl
      positions with leaving groups, has been proposed as a monochromophoric
      photocleavable linker. The attached groups can be disconnected selectively and
      orthogonally upon irradiation.

PMID- 20684514
TI  - Hydrido-ruthenium cluster complexes as models for reactive surface hydrogen
      species of ruthenium nanoparticles. Solid-state 2H NMR and quantum chemical
      calculations.
AB  - The (2)H quadrupolar interaction is a sensitive tool for the characterization of
      deuterium-metal binding states. In the present study, experimental solid-state
      (2)H MAS NMR techniques are used in the investigations of two ruthenium clusters,
      D(4)Ru(4)(CO)(12) (1) and D(2)Ru(6)(CO)(18) (2), which serve as model compounds
      for typical two-fold, three-fold, and octahedral coordination sites on metal
      surfaces. By line-shape analysis of the (2)H MAS NMR measurements of sample 1, a
      quadrupolar coupling constant of 67 +/- 1 kHz, an asymmetry parameter of 0.67 +/-
      0.1, and an isotropic chemical shift of -17.4 ppm are obtained. In addition to
      the neutral complex, sample 2 includes two ionic clusters, identified as anionic
      [DRu(6)(CO)(18)](-) (2(-)) and cationic [D(3)Ru(6)(CO)(18)](+) (2(+)). By virtue
      of the very weak quadrupolar interaction (<2 kHz) and the strong low-field shift
      (+16.8 ppm) of 2(-), it is shown that the deuteron is located in the symmetry
      center of the octahedron spanned by the six ruthenium atoms. For the cationic
      2(+), the quadrupolar interaction is similar to that of the neutral 2. Quantum
      chemical DFT calculations at different model structures for these ruthenium
      clusters were arranged in order to help in the interpretation of the experimental
      results. It is shown that the (2)H nuclear quadrupolar interaction is a sensitive
      tool for distinguishing the binding state of the deuterons to the transition
      metal. Combining the data from the polynuclear complexes with the data from
      mononuclear complexes, a molecular ruler for quadrupolar interactions is created.
      This ruler now permits the solid-state NMR spectroscopic characterization of
      deuterium adsorbed on the surfaces of catalytically active metal nanoparticles.

PMID- 20684515
TI  - Exploiting conformational dynamics to facilitate formation and trapping of
      electron-transfer photoproducts in metal complexes.
AB  - Three new photoinduced electron donor-acceptor (D-A) systems are reported which
      juxtapose a Ru(II) excited-state donor with a bipyridinium acceptor via a
      conformationally active asymmetric aryl-substituted bipyridine ligand
      participating in the bridge between D and A. Across the series of complexes 1-3,
      steric bulk is sequentially added to tune the inter-ring dihedral angle theta
      between the bipyridine and the aryl substituent. Driving forces for photoinduced
      electron transfer (DeltaG(ET)) and back electron transfer (DeltaG(BET)) are
      reported based on electrochemical measurements of 1-3 as well as Franck-Condon
      analysis of emission spectra collected for three new donor model complexes 1'-3'.
      These preserve the substitution patterns on the aryl substituent in their
      respective D-A complexes but remove the bipyridinium acceptor. Both DeltaG(ET)
      and DeltaG(BET) are invariant to within 0.02 eV across the series. Upon visible
      photoexcitation of each of the D-A systems with approximately 100 fs laser pulses
      at 500 +/- 10 nm, an electron-transfer (ET) photoproduct is observed to form with
      a time constant of tau(ET) = 29 ps (1), 37 ps (2), and 57 ps (3). That ET remains
      relatively rapid throughout this series, even as steric bulk significantly
      increases the inter-ring dihedral angle theta, is attributed to the effects of
      ligand-based torsional dynamics driven by intraligand electron delocalization in
      the D*-A excited state manifold prior to ET. The lifetimes of the charge
      separated states (tau(BET)) are also reported with tau(BET) = 98 ps (1), 217 ps
      (2), and 789 ps (3), representing a more than 8-fold increase across the series.
      This is attributed to reverse conformational dynamics in D(+)-A(-) driven by
      steric repulsions, which serves to minimize electronic coupling to the ground
      state. Steric control of ligand geometry and the range over which theta changes
      during conformational dynamics provides a new strategy to facilitate the
      formation and storage of charge-separated excited states.

PMID- 20684517
TI  - Self-assembly of a nanosized, saddle-shaped, solution-stable polyoxometalate
      anion built from pentagonal building blocks: [H34W119Se8Fe2O420]54-.
AB  - Precise control of the "one-pot" reaction conditions is employed for the assembly
      of a nanosized 2.8 nm cluster, [H(34)W(119)Se(8)Fe(2)O(420)](54-) (1a), which is
      templated using eight selenite units and two iron(III) centers. Not only is this
      cluster characterized structurally using X-ray crystallography, it is the largest
      polyoxotungstate to be observed intact in solution using ESI-MS, with a molecular
      mass of ca. 30,000 Da.

PMID- 20684516
TI  - Liquid chromatography-mass spectrometry-based parallel metabolic profiling of
      human and mouse model serum reveals putative biomarkers associated with the
      progression of nonalcoholic fatty liver disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) is the most common form of chronic liver
      disease in most western countries. Current NAFLD diagnosis methods (e.g., liver
      biopsy analysis or imaging techniques) are poorly suited as tests for such a
      prevalent condition, from both a clinical and financial point of view. The
      present work aims to demonstrate the potential utility of serum metabolic
      profiling in defining phenotypic biomarkers that could be useful in NAFLD
      management. A parallel animal model/human NAFLD exploratory metabolomics approach
      was employed, using ultra performance liquid chromatography-mass spectrometry
      (UPLC-MS) to analyze 42 serum samples collected from nondiabetic, morbidly obese,
      biopsy-proven NAFLD patients, and 17 animals belonging to the glycine N
      methyltransferase knockout (GNMT-KO) NAFLD mouse model. Multivariate statistical
      analysis of the data revealed a series of common biomarkers that were
      significantly altered in the NAFLD (GNMT-KO) subjects in comparison to their
      normal liver counterparts (WT). Many of the compounds observed could be
      associated with biochemical perturbations associated with liver dysfunction
      (e.g., reduced Creatine) and inflammation (e.g., eicosanoid signaling). This
      differential metabolic phenotyping approach may have a future role as a
      supplement for clinical decision making in NAFLD and in the adaption to more
      individualized treatment protocols.

PMID- 20684518
TI  - Electrochemically controlled adsorption of Fc-functionalized polymers on beta-CD
      modified self-assembled monolayers.
AB  - This work presents an in situ study of the adsorption/desorption behavior of
      ferrocene(Fc)-functionalized linear polymers on a gold surface covered with beta
      cyclodextrin(beta-CD)-modified self-assembled monolayers (SAMs). The
      characterization of binary SAMs obtained with HS-(CH(2))(11)-EG(6)-N(3) and HS
      (CH(2))(11)-EG(4)-OH (EG, ethylene glycol) was performed using a quartz crystal
      microbalance with dissipation monitoring (QCM-D), cyclic voltammetry, and contact
      angle measurements. The functionalization of SAMs with beta-CD was made via the
      "click" reaction between the beta-CD monoalkyne derivative and azide groups
      exhibited by SAMs. The formation of the host-guest complex between SAM-beta-CD
      and Fc-derivatized polymers (chitosan (CHI) and poly(allylamine hydrochloride)
      (PAH)) was studied by QCM-D. The viscoelastic model of Voinova was used to fit
      QCM-D curves recorded during the adsorption and electrochemically controlled
      desorption of CHI-Fc and PAH-Fc on SAM-beta-CD. Using QCM-D coupled to cyclic
      voltammetry, we demonstrated that CHI-Fc and PAH-Fc can be successfully deposited
      on a SAM-beta-CD-coated gold surface forming a stable multivalent inclusion
      complex between Fc moieties of polymer and beta-CD cavities of SAM. We also
      showed that all specifically attached polymer chains can be detached from the SAM
      beta-CD-coated gold surface by applying an electric field.

PMID- 20684519
TI  - Synthesis and biological evaluation of (+/-)-dinemasone C and analogues.
AB  - Dinemasone C was prepared in three steps (8% overall yield) from cis-tetrahydro-4
      hydroxy-6-methyl-2-pyrone by aldol reaction with 2,4-hexadienal, epoxidation
      followed by cyclization, and epimerization of the ring fusion. Dinemasone C, epi
      dinemasone C, anhydrodinemasone BC, and nor-dinemasone B are active against
      bacteria, including Legionella pneumophila Corby, algae, and fungi.

PMID- 20684520
TI  - High-throughput profiling of the serum N-glycome on capillary electrophoresis
      microfluidics systems: toward clinical implementation of GlycoHepatoTest.
AB  - We developed a 3 h procedure for preparing serum N-glycans and labeling them with
      8-aminopyrene-1,3,6-trisulfonic acid (APTS) by sequential addition of reagents to
      the serum and incubation in a polymerase chain reaction (PCR) thermocycler.
      Moreover, we succeeded in analyzing these samples by capillary electrophoresis on
      three commercial microfluidics-based platforms: the MCE-202 MultiNA, the 2100
      Bioanalyzer, and a modified prototype of the eGene system which were originally
      designed for nucleic acid separation and detection. Although these instruments
      use short separation channels, our technical improvements made it possible to
      reliably measure the N-glycans constituting GlycoHepatoTest. This test comprises
      a panel of biomarkers that allows follow-up of liver fibrosis patients starting
      from the early stage. In this way and for the first time, we demonstrate a
      clinical glycomics assay on an affordable, robust platform so that clinical
      chemistry laboratories can exploit glycomics in the diagnosis and monitoring of
      chronic liver disease. Another potential application is the rapid screening of
      the N-glycosylation of recombinant glycoproteins produced for pharmaceutical use.

PMID- 20684521
TI  - Radiocarbon dating of individual lignin phenols: a new approach for establishing
      chronology of late quaternary lake sediments.
AB  - The reliability of chronology is a prerequisite for meaningful paleoclimate
      reconstructions from sedimentary archives. The conventional approach of
      radiocarbon dating bulk organic carbon in lake sediments is often hampered by the
      old carbon effect, i.e., the assimilation of ancient dissolved inorganic carbon
      (DIC) derived from carbonate bedrocks or other sources. Therefore, radiocarbon
      dating is ideally performed on organic compounds derived from land plants that
      use atmospheric CO(2) and rapidly delivered to sediments. We demonstrate that
      lignin phenols isolated from lake sediments using reversed phase high performance
      liquid chromatography (HPLC) can serve as effective (14)C dating materials for
      establishing chronology during the late Quaternary. We developed a procedure to
      purify lignin phenols, building upon a published method. By isolating lignin from
      standard wood reference substances, we show that our method yields pure lignin
      phenols and consistent ages as the consensus ages and that our procedure does not
      introduce radiocarbon contamination. We further demonstrate that lignin phenol
      ages are compatible with varve counted and macrofossil dated sediment horizons in
      Steel Lake and Fayetteville Green Lake. Applying the new method to lake sediment
      cores from Lake Qinghai demonstrates that lignin phenol ages in Lake Qinghai are
      consistently younger than bulk total organic carbon (TOC) ages which are
      contaminated by old carbon effect. We also show that the age offset between
      lignin and bulk organic carbon differs at different Lake Qinghai sedimentary
      horizons, suggesting a variable hard water effect at different times and that a
      uniform age correction throughout the core is inappropriate.

PMID- 20684522
TI  - Quartz nanopore membranes for suspended bilayer ion channel recordings.
AB  - A method is described for fabricating 25-75 mum thick fused quartz membranes
      containing a single conical shaped nanopore (orifice radius ranging from 10 to
      1000 nm). The quartz nanopore membrane (QNM) provides an excellent solid support
      structure for lipid bilayers in ion channel recordings due to the large
      electrical resistivity of fused quartz. Electrical measurements demonstrate that
      the leakage current through 1,2-diphytanoyl-sn-glycero-3-phosphocholine (DPhPC)
      bilayers suspended across a 500-1000 nm radius QNM orifice is immeasurably small,
      corresponding to a bilayer resistance greater than 10(12) ohms. Translocation of
      single-stranded DNA oligomers (poly dA 50-mer and poly dA 20-mer) through a
      protein ion channel (alpha-hemolysin) reconstituted in a DPhPC bilayer suspended
      across the QNM orifice is demonstrated.

PMID- 20684523
TI  - Detection of carbohydrate binding proteins using magnetic relaxation switches.
AB  - We have developed a simple, rapid, and sensitive carbohydrate-based magnetic
      relaxation switch assay for the detection of carbohydrate binding proteins. This
      technique was used to detect lectins and toxins that are known to bind to
      specific carbohydrates. Lectins that bind to the same carbohydrate displayed
      differential aggregation profiles because of differences in the structure and
      number of binding sites of the lectins. We demonstrated that selectivity and
      sensitivity can be enhanced using two different recognition elements. We have
      also demonstrated that magnetic relaxation switch assays can be used to detect
      toxins in a complex medium such as stool and environmental samples.

PMID- 20684524
TI  - Mutation at a strictly conserved, active site tyrosine in the copper amine
      oxidase leads to uncontrolled oxygenase activity.
AB  - The copper amine oxidases carry out two copper-dependent processes: production of
      their own redox-active cofactor (2,4,5-trihydroxyphenylalanine quinone, TPQ) and
      the subsequent oxidative deamination of substrate amines. Because the same active
      site pocket must facilitate both reactions, individual active site residues may
      serve multiple roles. We have examined the roles of a strictly conserved active
      site tyrosine Y305 in the copper amine oxidase from Hansenula polymorpha
      kinetically, spetroscopically (Dubois and Klinman (2006) Biochemistry 45, 3178),
      and, in the present work, structurally. While the Y305A enzyme is almost
      identical to the wild type, a novel, highly oxygenated species replaces TPQ in
      the Y305F active sites. This new structure not only provides the first direct
      detection of peroxy intermediates in cofactor biogenesis but also indicates the
      critical control of oxidation chemistry that can be conferred by a single active
      site residue.

PMID- 20684525
TI  - In situ electrochemical imaging of membrane glycan expression on micropatterned
      adherent single cells.
AB  - A scanning electrochemical microscopic (SECM) method for in situ imaging of four
      types of membrane glycan motifs on single adherent cells was proposed using BGC
      823 human gastric carcinoma (BGC) cells as the model. These adherent cells were
      first micropatterned in the microwell of poly(dimethylsiloxane) membrane for
      precisely controlling the localized surface interaction, and the membrane glycans
      were then specifically recognized with corresponding lectins labeled with
      horseradish peroxidase (HRP). On the basis of the enzymatic oxidization of
      ferrocenylmethanol (FMA) by H(2)O(2) to yield FMA(+), the glycan expression level
      was detected by the reduction current of FMA(+) at the SECM tip. The cell-surface
      glycans could, thus, be in situ imaged by SECM at a single-cell level without
      peeling the cells from culture dish. Under the optimized conditions, four types
      of membrane glycan motifs showed statistically distinguishable expression levels.
      The SECM results for different glycan motifs on adherent single cells were
      consistent with those estimated by flow cytometric assay. This work provides a
      reliable approach for in situ evaluation of the characteristic glycopattern of
      single living cells and can be applied in cell biologic study based on cell
      surface carbohydrate expression.

PMID- 20684526
TI  - Effect of spatial charge inhomogeneity on 1/f noise behavior in graphene.
AB  - Scattering mechanisms in graphene are critical to understanding the limits of
      signal-to-noise ratios of unsuspended graphene devices. Here we present the four
      probe low-frequency noise (1/f) characteristics in back-gated single layer
      graphene (SLG) and bilayer graphene (BLG) samples. Contrary to the expected noise
      increase with the resistance, the noise for SLG decreases near the Dirac point,
      possibly due to the effects of the spatial charge inhomogeneity. For BLG, a
      similar noise reduction near the Dirac point is observed, but with a different
      gate dependence of its noise behavior. Some possible reasons for the different
      noise behavior between SLG and BLG are discussed.

PMID- 20684527
TI  - Indirect magnetic coupling in light-element-doped single-walled carbon nanotubes.
AB  - Single-walled carbon nanotubes substitutionally doped with the light-element
      phosphorus are synthesized and are investigated by electrical and nuclear
      magnetic resonance measurements. Decreased spin-lattice relaxation times compared
      to undoped tubes point toward enhanced spin-sensitive scattering. Temperature
      dependence of the zero-bias conductance shows step-like features, a signature of
      scattering from a very low density (few sites per nanotube) of localized spin
      moments at oxidized phosphorus sites, consistent with density functional
      calculations. This supports recent predictions that localized magnetic moments
      must be indirectly magnetically coupled through the nanotube conduction
      electrons.

PMID- 20684528
TI  - Graphene in mice: ultrahigh in vivo tumor uptake and efficient photothermal
      therapy.
AB  - Although biomedical applications of carbon nanotubes have been intensively
      studied in recent years, its sister, graphene, has been rarely explored in
      biomedicine. In this work, for the first time we study the in vivo behaviors of
      nanographene sheets (NGS) with polyethylene glycol (PEG) coating by a fluorescent
      labeling method. In vivo fluorescence imaging reveals surprisingly high tumor
      uptake of NGS in several xenograft tumor mouse models. Distinctive from PEGylated
      carbon nanotubes, PEGylated NGS shows several interesting in vivo behaviors
      including highly efficient tumor passive targeting and relatively low retention
      in reticuloendothelial systems. We then utilize the strong optical absorbance of
      NGS in the near-infrared (NIR) region for in vivo photothermal therapy, achieving
      ultraefficient tumor ablation after intravenous administration of NGS and low
      power NIR laser irradiation on the tumor. Furthermore, no obvious side effect of
      PEGylated NGS is noted for the injected mice by histology, blood chemistry, and
      complete blood panel analysis in our pilot toxicity study. Although a lot more
      efforts are required to further understand the in vivo behaviors and the long
      term toxicology of this new type of nanomaterials, our work is the first success
      of using carbon nanomaterials for efficient in vivo photothermal therapy by
      intravenous administration and suggests the great promise of graphene in
      biomedical applications, such as cancer treatment.

PMID- 20684529
TI  - Flavonoids in the poisonous plant Oxytropis falcata.
AB  - Three new flavonoids, oxytropisoflavans A (1) and B (2) and (6aR,11aR)-3,8
      dihydroxy-9,10-dimethoxypterocarpan (3), together with 30 known flavonoids (4
      33), were isolated from the aerial parts and roots of Oxytropis falcata. The
      absolute configurations of 3 and C-3 in 1 and 2 were deduced by circular
      dichroism. The structure of flavonoid 2 was confirmed by single-crystal X-ray
      diffraction analysis and that of flavonoid 3 by total synthesis of its racemate.
      Oxytropisoflavan A (1) is an unprecedented chalcan-isoflavan biflavonoid, whereas
      oxytropisoflavan B (2) possesses a rare modified A-ring. Pterocarpan 3 has good
      radical-scavenging activity in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay.

PMID- 20684530
TI  - Carbon nanotube doping mechanism in a salt solution and hygroscopic effect:
      density functional theory.
AB  - The mechanism of doping carbon nanotubes (CNTs) with a salt solution was
      investigated using the density functional theory. We propose that the anion-CNT
      complex is a key component in doping CNTs. Although the cations play an important
      role in ionizing CNTs as an intermediate precursor, the ionized CNTs are
      neutralized further by forming a stable anion-CNT complex as a final reactant.
      The anion-CNT bond has a strong ionic bonding character and clearly shows p-type
      behavior by shifting the Fermi level toward the valence band. The midgap state is
      introduced by the strong binding of carbon and anion atoms. These localized
      charged anion sites are highly hygroscopic and induce the adsorption of water
      molecules. This behavior provides a new possibility for using anion
      functionalized CNTs as humidity sensors.

PMID- 20684531
TI  - Cu-catalyzed double S-alkenylation of potassium sulfide: a highly efficient
      method for the synthesis of various thiophenes.
AB  - An efficient synthetic approach to variously substituted thiophenes has been
      developed through copper-catalyzed tandem S-alkenylation of potassium sulfide
      with 1,4-diiodo-1,3-dienes.

PMID- 20684532
TI  - Neutral coatings for the study of polycation/multicharged anion interactions by
      capillary electrophoresis: application to dendrigraft poly-L-lysines with
      negatively multicharged molecules.
AB  - The study of interactions between oppositely multicharged (macro)molecules
      remains a challenging issue. In frontal analysis capillary electrophoresis
      (FACE), it is difficult to avoid the adsorption of one of the interacting
      partners onto the capillary wall. In this work, we demonstrate the possibility to
      use FACE and affinity capillary electrophoresis (ACE) on a neutrally coated
      capillary for the study of interactions between a polycationic dendrigraft (or
      linear) poly-l-lysines, on one hand, and a multicharged anionic biomolecule
      (adenosine monophosphate, AMP, or adenosine triphosphate, ATP), on the other
      hand. A systematic comparison of four different neutral coatings (hydroxypropyl
      cellulose, polydimethylacrylamide, polyacrylamide, polyethylene glycol) has been
      performed based on the repeatability of the electrophoretic migration of the
      dendrigraft poly-l-lysines at pH close to neutrality. Both FACE and ACE
      methodogies were then used to study the interactions and to get the association
      constants and the stoichiometry of the complex. Multisite interactions, with two
      classes of independent sites, were determined. The specificity of the dendritic
      polylysine structure compared with linear polylysine in the interaction with ATP
      or AMP is also emphasized.

PMID- 20684533
TI  - Ca(2+) sensor GCAP1: A constitutive element of the ONE-GC-modulated odorant
      signal transduction pathway.
AB  - In a small subset of the olfactory sensory neurons, the odorant receptor ONE-GC
      guanylate cyclase is a central transduction component of the cyclic GMP signaling
      pathway. In a two-step transduction model, the odorant, uroguanylin, binds to the
      extracellular domain and activates its intracellular domain to generate the
      odorant second messenger, cyclic GMP. This study via comprehensive technology,
      including gene deletion, live cell Forster resonance energy transfer (FRET), and
      surface plasmon resonance (SPR) spectroscopy, documents the identity of a
      remarkably intriguing operation of a Ca(2+) sensor component of the ONE-GC
      transduction machinery, GCAP1. In the ciliary membranes, the sites of odorant
      transduction, GCAP1 is biochemically and physiologically coupled to ONE-GC.
      Strikingly, this coupling reverses its well- established function in ROS-GC1
      signaling, linked with phototransduction. In response to the free Ca(2+) range
      from nanomolar to semimicromolar, it inhibits ROS-GC1, yet in this range, it
      incrementally stimulates ONE-GC. These two opposite modes of signaling two
      SENSORY processes by a single Ca(2+) sensor define a new transduction paradigm of
      membrane guanylate cyclases. This paradigm is pictorially presented.

PMID- 20684535
TI  - Polymer-supported pentaethylene glycol as a facile heterogeneous catalyst for
      nucleophilic fluorination.
AB  - Polymer-supported pentaethylene glycols (PSpentaEG) as promising catalysts for
      nucleophilic fluorination with alkali metal fluoride (MF) could significantly
      enhance the nucleophilicity of MF and provide simple purification and recycling
      in the reaction. Furthermore, by their synergistic effect, the combination of
      PSpentaEG and a tert-alcohol media system showed tremendous efficiency in the
      fluorination of base-sensitive substrates such as sec-alkyl halide.

PMID- 20684534
TI  - Origin of light-induced spin-correlated radical pairs in cryptochrome.
AB  - Blue-light excitation of cryptochromes and homologues uniformly triggers electron
      transfer (ET) from the protein surface to the flavin adenine dinucleotide (FAD)
      cofactor. A cascade of three conserved tryptophan residues has been considered to
      be critically involved in this photoreaction. If the FAD is initially in its
      fully oxidized (diamagnetic) redox state, light-induced ET via the tryptophan
      triad generates a series of short-lived spin-correlated radical pairs comprising
      an FAD radical and a tryptophan radical. Coupled doublet-pair species of this
      type have been proposed as the basis, for example, of a biological magnetic
      compass in migratory birds, and were found critical for some cryptochrome
      functions in vivo. In this contribution, a cryptochrome-like protein (CRYD)
      derived from Xenopus laevis has been examined as a representative system. The
      terminal radical-pair state FAD(*)...W324(*) of X. laevis CRYD has been
      characterized in detail by time-resolved electron-paramagnetic resonance (TREPR)
      at X-band microwave frequency (9.68 GHz) and magnetic fields around 345 mT, and
      at Q-band (34.08 GHz) at around 1215 mT. Different precursor states, singlet
      versus triplet, of radical-pair formation have been considered in spectral
      simulations of the experimental electron-spin polarized TREPR signals.
      Conclusively, we present evidence for a singlet-state precursor of
      FAD(*)...W324(*) radical-pair generation because at both magnetic fields, where
      radical pairs were studied by TREPR, net-zero electron-spin polarization has been
      detected. Neither a spin-polarized triplet precursor nor a triplet at thermal
      equilibrium can explain such an electron-spin polarization. It turns out that a
      two-microwave-frequency TREPR approach is essential to draw conclusions on the
      nature of the precursor electronic states in light-induced spin-correlated
      radical pair formations.

PMID- 20684536
TI  - Structure and in vitro digestibility of normal corn starch: effect of acid
      treatment, autoclaving, and beta-amylolysis.
AB  - The goal of this study was to explore a new strategy to reduce the digestibility
      of normal corn starch (NCS). NCS was treated using 1.0% hydrogen chloride at 55
      degrees C. After neutralization and desalting, starches were adjusted to 35%
      moisture content and subjected to autoclaving. Thereafter, starches were
      subjected to beta-amylolysis. At different stages, starches were characterized
      for chain length distribution, ordered structure including the crystalline
      pattern, and in vitro digestibility. The results showed that acid treatment
      reduced amylose molecular weight and increased the thermal resistance of A-type
      crystallites. V-type crystallites promoted by autoclaving were increased by acid
      treatment, suggesting the beneficial effect of reduced amylose molecular weight
      on crystallization. beta-Amylolysis had minor impact on the crystalline pattern;
      however, it significantly reduced the in vitro digestibility of starch by
      enriching linear chains. At higher levels of acid treatment, the effect of beta
      amylolysis was more pronounced.

PMID- 20684537
TI  - Concerted proton-electron transfer to dioxygen in water.
AB  - Concerted proton-electron transfer (CPET) is documented for the homogeneous
      reduction of O(2) to HO(2)(*) in water by the one-electron-reduced
      heteropolytungstate anion, alpha-PW(12)O(40)(4-) (1(1e)). At 0.01-0.3 M H(+),
      O(2) reduction occurs via outer-sphere electron transfer followed by proton
      transfer (ETPT, with rate constant k(ET)). Between 0.30 and 1.9 M H(+), rates
      increase linearly with [H(+)] due to a parallel CPET pathway in which H(+) is now
      a reactant: (1/2)k(obs) = k(ET) + k(CPET)[H(+)] (k(ET) = 1.2 M(-1) s(-1); k(CPET)
      = 0.8 M(-2) s(-1)). Control experiments rule out preassociation between H(+) and
      1(1e). Analysis of plausible rate expressions shows that the first-order
      dependence on [H(+)] is uniquely consistent with multisite CPET, and a deuterium
      kinetic isotope effect of 1.7 is observed. Reductions of O(2) by alpha
      SiW(12)O(40)(5-) confirm theoretical predictions that CPET decreases in
      significance as ET becomes less endergonic. Marcus analysis, including the
      temperature dependence of DeltaG(o), gives reorganization energies, lambda(ET) =
      41.5 kcal mol(-1) and lambda(CPET) = 52.4 kcal mol(-1). At 1.5 M H(+),
      approximately 75% of the (1(1e),O(2)) encounter pairs form within 6 A of H(+)
      ions. This value (6 +/- 1 A) is the "reaction distance" for proton diffusion and
      probably close to that for CPET. Even so, the 70-200 ps lifetimes of the
      (1(1e),O(2)) pairs provide additional time for H(+) to diffuse closer to O(2).
      CPET is first-order in [H(+)] because k(e) for "cage escape" from (1(1e),O(2))
      pairs is much larger than k(CPET), such that the rate expression for CPET becomes
      -(1/2)d[1(1e)]/dt = (k(d)/k(e))k(CPET)[1(1e)][O(2)][H(+)], where k(d) is the rate
      constant for (1(1e),O(2)) pair formation. Overall, the findings suggest that the
      emergence of CPET, with hydronium ion as the proton donor, may prove a general
      feature of sufficiently endergonic reductions of dioxygen by otherwise "outer
      sphere" complexes (or electrode reactions) at sufficiently low pH values in
      water.

PMID- 20684538
TI  - Cyclic alternating ring-opening metathesis polymerization (CAROMP). Rapid access
      to functionalized cyclic polymers.
AB  - Catalysis of alternating ROMP with (H(2)IMes)Cl(2)Ru=CHPh(OiPr), the second
      generation Hoveyda-Grubbs catalyst, provided an entirely cyclic alternating
      polymer. Conditions for the cyclic AROMP were used to prepare a polymer in which
      one of the repeat units bore a primary alkyl chloride that was used for further
      elaboration.

PMID- 20684539
TI  - Catalytic regioselective synthesis of structurally diverse indene derivatives
      from N-benzylic sulfonamides and disubstituted alkynes.
AB  - An unprecedented protocol has been developed for the regioselective synthesis of
      structurally diverse indene derivatives from readily accessible N-benzylic
      sulfonamides and disubstituted alkynes through FeCl(3)-catalyzed cleavage of
      sp(3) carbon-nitrogen bonds to generate benzyl cation intermediates. In the
      presence of 10 mol % of FeCl(3), a broad range of N-benzylic sulfonamides
      smoothly react with internal alkynes, alkynylcarbonyl compounds, alkynyl
      chalcogenides, or alkynyl halides to afford various functionalized indene
      derivatives with extremely high regioselectivity.

PMID- 20684540
TI  - Lactones and quinones from the tubers of Sinningia aggregata.
AB  - Three new aromatic epsilon-lactones, aggregatins A (1), B (2), and C (3), a new
      naphthoquinone derivative, aggregatin D (4), and three known anthraquinones, 2
      methylanthraquinone, 7-methoxy-2-methylanthraquinone, and 7-hydroxy-2
      methylanthraquinone, were isolated from the tubers of Sinningia aggregata
      (Gesneriaceae). Compounds 1 and 4 and the anthraquinones showed marginal
      antimicrobial activity.

PMID- 20684541
TI  - High-resolution local imaging of temperature in dielectrophoretic platforms.
AB  - The use of dielectrophoretic forces is crucially tied to the knowledge of Joule
      heating within a fluid, since the use of planar microelectrodes creates a
      temperature gradient within which the particle of interest is manipulated.
      Mapping temperature with sufficient spatial resolution within a dielectrophoretic
      trap is recognized to be of high importance. Herein, we demonstrate local
      temperature measurements in the vicinity of a trapped micrometer-size particle
      using confocal fluorescence spectroscopy. Such measurements are shown to provide
      a novel calibration tool for screening temperature-mediated processes with high
      resolution.

PMID- 20684542
TI  - Amino-alcohol ligands: synthesis and structure of N,N'-bis(2
      hydroxycyclopentyl)ethane-1,2-diamine and its salts, and an assessment of its
      fitness and that of related ligands for complexing metal ions.
AB  - The synthesis and solid state structure of the amino-alcohol ligand,
      (1R,2R,1'S,2'S)-N,N'-bis(2-hydroxycyclopentyl)ethane-1,2-diamine (Cyp(2)en)
      obtained by the reaction of cyclopentene oxide with ethylenediamine, as well as
      its bromide, chloride, perchlorate, and nitrate salts, is reported. In all five
      structures, the Cyp(2)en ligand sits on a center of inversion with the two amino
      groups and two hydroxyl groups of the cyclopentyl moieties trans to each other
      across that inversion center. Comparing this conformation to that of a density
      functional theory (DFT)-calculated structure of cis-[Ni(Cyp(2)en)(H(2)O)(2)](2+)
      suggests that the ligand is not well pre-organized for coordinating a metal ion.
      The likely solution structure of this ligand, and that of the related ligands
      bis(2-hydroxy)ethane-1,2-diamine (Bheen) and bis(2-hydroxycyclohexyl)ethane-1,2
      diamine (Cy(2)en), was explored using molecular mechanics modeling with the
      generalized AMBER force field. A Boltzmann distribution of the lowest energy
      conformations found shows that 36 conformations of Bheen each contribute more
      than 1% to the population at 300 K; this decreases to 27 conformations for
      Cyp(2)en and to 12 for Cy(2)en, and Cy(2)en is the most rigid of the three
      ligands. The population-weighted root-mean-square deviation (rmsd) between these
      lowest energy conformations and the conformation required for coordinating a
      metal ion increased in the order Cy(2)en < Cyp(2)en < Bheen, while stability
      constants for coordinating Ni(II) decrease in the order Cy(2)en > Bheen >
      Cyp(2)en. The high pre-organization of Cy(2)en is due to an intramolecular N
      H....O hydrogen bond, apparently missing in the other two ligands. Pre
      organization is likely to be an important, but not the only factor, that controls
      the value of the stability constants of these ligands with metal ions.

PMID- 20684543
TI  - Cellular internalization kinetics of (luciferin-)cell-penetrating peptide
      conjugates.
AB  - Cell-penetrating peptides (CPPs) belong to a class of delivery vectors that have
      been extensively used for the cellular delivery of various, otherwise
      impermeable, macromolecules. However, results on the cellular internalization
      efficacy of CPPs obtained from various laboratories are sometimes challenging to
      compare because of differences in the experimental setups. Here, for the first
      time, the cellular uptake kinetics of eight well-established CPPs is compared in
      HeLa pLuc 705 cells using a recently published releasable luciferin assay. Using
      this assay, the kinetic behavior of cytosolic entry of these luciferin-CPP
      conjugates are registered in real time. Our data reveal that the uptake rate of
      CPPs reaches its maximum either in seconds or in tens of minutes, depending on
      the CPP used. Tat and higher concentrations of MAP and TP10 display fast
      internalization profiles that resemble the kinetic profile of membrane-permeable
      free luciferin. The uptake of the other peptides, pVec, penetratin, M918, and
      EB1, is much slower and is consistent with the reported observations of
      endocytosis being the predominant internalization mechanism. Additionally, to
      some extent, the latter CPPs can be clustered into subgroups which are based on
      time points when the most pronounced uptake rates are observed. This may indicate
      once more involvement of various (concentration dependent) mechanisms in the
      uptake of CPPs. In summary, the variances in the internalization profiles for the
      CPPs demonstrate the importance of measuring kinetics instead of only relying on
      simple end-point studies, and with the luciferin-CPP assay, more lucid
      information can be retrieved when studying the internalization mechanisms of
      CPPs.

PMID- 20684545
TI  - MacroSEQUEST: efficient candidate-centric searching and high-resolution
      correlation analysis for large-scale proteomics data sets.
AB  - Modern mass spectrometers are now capable of producing tens of thousands of
      tandem mass (MS/MS) spectra per hour of operation, resulting in an ever
      increasing burden on the computational tools required to translate these raw
      MS/MS spectra into peptide sequences. In the present work, we describe our
      efforts to improve the performance of one of the earliest and most commonly used
      algorithms, SEQUEST, through a wholesale redesign of its processing architecture.
      We call this new program MacroSEQUEST, which exhibits a dramatic improvement in
      processing speed by transiently indexing the array of MS/MS spectra prior to
      searching FASTA databases. We demonstrate the performance of MacroSEQUEST
      relative to a suite of other programs commonly encountered in proteomics
      research. We also extend the capability of SEQUEST by implementing a parameter in
      MacroSEQUEST that allows for scalable sparse arrays of experimental and
      theoretical spectra to be implemented for high-resolution correlation analysis
      and demonstrate the advantages of high-resolution MS/MS searching to the
      sensitivity of large-scale proteomics data sets.

PMID- 20684544
TI  - Substrate affinity of photosensitizers derived from chlorophyll-a: the ABCG2
      transporter affects the phototoxic response of side population stem cell-like
      cancer cells to photodynamic therapy.
AB  - Photosensitizers (PS) synthesized with the aim of optimizing photodynamic therapy
      (PDT) of tumors do not always fulfill their potential when tested in vitro and in
      vivo in different tumor models. The ATP-dependent transporter ABCG2, a multidrug
      resistant pump expressed at variable levels in cancerous cells, can bind and
      efflux a wide range of structurally different classes of compounds including
      several PS used preclinically and clinically such as porphyrins and chlorins.
      ABCG2 may lower intracellular levels of substrate PS below the threshold for cell
      death in tumors treated by PDT, leaving resistant cells to repopulate the tumor.
      To determine some of the structural factors that affect substrate affinity of PS
      for ABCG2, we used an ABCG2-expressing cell line (HEK 293 482R) and its
      nonexpressing counterpart, and tyrosine kinase ABCG2 inhibitors in a simple flow
      cytometric assay to identify PS effluxed by the ABCG2 pump. We tested a series of
      conjugates of substrate PS with different groups attached at different positions
      on the tetrapyrrole macrocycle to examine whether a change in affinity for the
      pump occurred and whether such changes depended on the position or the
      structure/type of the attached group. PS without substitutions including
      pyropheophorbides and purpurinimides were generally substrates for ABCG2, but
      carbohydrate groups conjugated at positions 8, 12, 13, and 17 but not at position
      3 abrogated ABCG2 affinity regardless of structure or linking moiety. At position
      3, affinity was retained with the addition of iodobenzene, alkyl chains and
      monosaccharides, but not with disaccharides. This suggests that structural
      characteristics at position 3 may offer important contributions to requirements
      for binding to ABCG2. We examined several tumor cell lines for ABCG2 activity,
      and found that although some cell lines had negligible ABCG2 activity in bulk,
      they contained a small ABCG2-expressing side population (SP) thought to contain
      cells which are responsible for initiating tumor regrowth. We examined the
      relevance of the SP to PDT resistance with ABCG2 substrates in vitro and in vivo
      in the murine mammary tumor 4T1. We show for the first time in vivo that the
      substrate PS HPPH (2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a) but not the
      nonsubstrate PS HPPH-Gal (a galactose conjugate of HPPH) selectively preserved
      the SP which was primarily responsible for regrowth in vitro. The SP could be
      targeted by addition of imatinib mesylate, a tyrosine kinase inhibitor which
      inhibits the ATPase activity of ABCG2, and prevents efflux of substrates. A PDT
      resistant SP may be responsible for recurrences observed both preclinically and
      clinically. To prevent ABCG2 mediated resistance, choosing nonsubstrate PS or
      administering an ABCG2 inhibitor alongside a substrate PS might be advantageous
      when treating ABCG2-expressing tumors with PDT.

PMID- 20684546
TI  - Engineering of the heme pocket of an H-NOX domain for direct cyanide detection
      and quantification.
AB  - A new cyanide sensing system, the Heme-Nitric oxide and/or OXygen binding domain
      (H-NOX domain) from Thermoanaerobacter tengcongensis (Tt H-NOX), has been
      investigated. With straightforward absorbance-based detection, we have achieved a
      cyanide detection limit of 0.5 microM (approximately 10 ppb) with an upper
      detection range that is adjustable with protein concentration. We find a linear
      correlation of multiple spectroscopic features with cyanide concentration. These
      spectroscopic features include the Soret band maximum and absorbance changes in
      both the Soret and alpha/beta band regions of the spectrum. Multiple probes for
      cyanide detection makes sensing with Tt H-NOX unique compared to other cyanide
      sensing methods. Furthermore, using site-directed mutagenesis, we have rationally
      engineered the heme pocket of Tt H-NOX to improve its cyanide sensing properties.
      Using a mutant that alters the heme structure of Tt H-NOX (P115A) we were able to
      introduce colorimetric detection of cyanide. Through substituting phenylalanine
      78 with a smaller (valine, F78V) or a larger residue (tyrosine, F78Y), we
      demonstrate a correlation with distal pocket steric crowding and affinity for
      cyanide. In particular, F78V Tt H-NOX shows a significant increase in CN(-)
      binding affinity and selectivity. Thus, we demonstrate the ability to fine-tune
      the affinity and specificity of Tt H-NOX for cyanide, suggesting that Tt H-NOX
      can be readily tailored into a practical cyanide sensor.

PMID- 20684547
TI  - Interaction of a food-grade cationic surfactant (lauric arginate) with food-grade
      biopolymers (pectin, carrageenan, xanthan, alginate, dextran, and chitosan).
AB  - Lauric arginate (LAE) is a food-grade cationic surfactant that is a highly potent
      antimicrobial active against a wide range of food pathogens and spoilage
      organisms. In compositionally complex environments, the antimicrobial activity of
      cationic LAE is likely to be impacted by its interactions with other charged
      components. The purpose of this study was to characterize the interactions
      between cationic LAE and various food grade biopolymers with different charge
      characteristics: anionic (pectin, alginate, carrageenan, xanthan), neutral
      (dextran), and cationic (chitosan). Isothermal titration calorimetry (ITC) and
      turbidity measurements were used to characterize surfactant-biopolymer
      interactions and the solubility of any aggregates formed. ITC and turbidity
      measurements suggested that no complex formation occurred between the cationic
      LAE and the cationic or neutral biopolymers, although the critical micelle
      concentration (cmc) of the surfactant was changed because of excluded volume
      effects. On the other hand, ITC measurements indicated a strong binding
      interaction between cationic LAE and anionic biopolymers. The amount of
      surfactant bound and the solubility of the aggregates formed depended strongly on
      biopolymer type. The results of this study have important implications for the
      application of LAE in compositionally complex systems.

PMID- 20684548
TI  - Diffusion of metal in a confined nanospace of carbon nanotubes induced by air
      oxidation.
AB  - Air oxidation can result in the motion of metal confined in carbon nanotubes
      (CNTs). This can also be utilized to tailor various hybrid nanostructures. By
      controllable air-oxidation, as-prepared metal@CNT nanorods (a) can be converted
      first to core-shell-void nanorods (b), then to metal/metal oxide@CNT nanotubes
      (c), and finally to mesoporous metal oxide nanotubes (d). The metal/metal
      oxide@CNT nanotubes and mesoporous metal oxide nanotubes are expected to find
      many applications, such as in lithium ion batteries, catalysis, magnetic drug
      delivery, and gas sensing.

PMID- 20684549
TI  - Discovery of a potent, selective, and orally bioavailable pyridinyl-pyrimidine
      phthalazine aurora kinase inhibitor.
AB  - The discovery of aurora kinases as essential regulators of cell division has led
      to intense interest in identifying small molecule aurora kinase inhibitors for
      the potential treatment of cancer. A high-throughput screening effort identified
      pyridinyl-pyrimidine 6a as a moderately potent dual inhibitor of aurora kinases 
      A and -B. Optimization of this hit resulted in an anthranilamide lead (6j) that
      possessed improved enzyme and cellular activity and exhibited a high level of
      kinase selectivity. However, this anthranilamide and subsequent analogues
      suffered from a lack of oral bioavailability. Converting the internally hydrogen
      bonded six-membered pseudo-ring of the anthranilamide to a phthalazine (8a-b) led
      to a dramatic improvement in oral bioavailability (38-61%F) while maintaining the
      potency and selectivity characteristics of the anthranilamide series. In a COLO
      205 tumor pharmacodynamic assay measuring phosphorylation of the aurora-B
      substrate histone H3 at serine 10 (p-histone H3), oral administration of 8b at 50
      mg/kg demonstrated significant reduction in tumor p-histone H3 for at least 6 h.

PMID- 20684550
TI  - Palladium-catalyzed dehydrohalogenative polycondensation of 2-bromo-3
      hexylthiophene: an efficient approach to head-to-tail poly(3-hexylthiophene).
AB  - Dehydrohalogenative polycondensation of 2-bromo-3-hexylthiophene was successful
      with Herrmann's catalyst and tris(2-dimethylaminophenyl)phosphine as catalyst
      precursors, giving head-to-tail poly(3-hexylthiophene) (HT-P3HT) with high
      molecular weight (M(n) = 30,600, M(w)/M(n) = 1.60) and high regioregularity (98%)
      in almost quantitative yield (99%).

PMID- 20684552
TI  - Poly(ethylene oxide) (PEO) and poly(vinyl pyrolidone) (PVP) induce different
      changes in the colloid stability of nanoparticles.
AB  - The phase behavior of model polymer-colloid mixtures is measured for solutions
      approaching the "protein limit", that is, when the radius of gyration of the
      polymer (R(g)) is greater than or approximately equal to the radius of the
      colloid (R). Cationic nanoparticles are mixed with poly(ethylene oxide) (PEO) or
      poly(vinyl pyrolidone) (PVP) at size ratios of R(g)/R = 0.7 and 1.8. The addition
      of PEO to stable nanoparticle dispersions leads to depletion flocculation in both
      deionized water and buffer solutions. The instability mechanism for the PVP
      nanoparticle system depends on the suspension medium. In water, bridging occurs
      below the saturation adsorption of PVP, whereas depletion phase separation is
      evident at concentrations exceeding those necessary to saturate the particle
      surface. In acidic buffer, PVP addition results in depletion phase separation.
      The difference between bridging and depletion is distinguished by both visual
      appearances and rheological measurements. There is no trend (within error bars)
      in the polymer concentration required to induce instability with increasing
      R(g)/R in contrast with theoretical predictions. This is most likely due to
      adsorption of polymer onto the particle surface.

PMID- 20684551
TI  - Nonpeptidic and potent small-molecule inhibitors of cIAP-1/2 and XIAP proteins.
AB  - A series of compounds were designed and synthesized as antagonists of cIAP-1/2
      and XIAP based upon our previously identified lead compound SM-122 (1). The most
      potent of these (7) binds to XIAP, cIAP-1, and cIAP-2 proteins with K(i) values
      of 36, <1, and <1.9 nM, respectively. Consistent with its potent binding
      affinities to IAPs, 7 effectively antagonizes XIAP in a cell-free caspase-9
      functional assay, efficiently induces cIAP-1 degradation in cells at
      concentrations as low as 10 nM, and triggers activation of caspases and PARP
      cleavage in the MDA-MB-231 breast cancer cell line. Compound 7 potently inhibits
      cell growth in the MDA-MB-231 cancer cell line with an IC(50) value of 200 nM and
      is 9 times more potent than compound 1.

PMID- 20684553
TI  - Effects of dermal exposure to Nicotiana tabacum (Jean Nicot, 1560) leaves in
      mouse evaluated by multiple methods and tissues.
AB  - Tobacco farmers are routinely exposed to complex mixtures of the compounds
      present in tobacco leaves, including organic and inorganic pesticides.
      Penetration through skin is the most significant route of uptake in occupational
      exposure to chemicals, including dust and liquids containing toxic and
      carcinogenic substances. This study evaluates the genotoxic effect of tobacco
      leaves with and without dermal exposure to flumetralin in Mus musculus,
      determining cell damage by the micronucleus test and the Comet assay as well as
      antioxidant enzyme activities and hematologic parameters. Nicotine was used as
      positive control. Blood samples were collected for 0, 3, 24 and 48 h exposure
      periods, and DNA damage by Comet assay and micronucleus test was evaluated for
      all these periods. Bone marrow and liver cells were also evaluated for the 48 h
      exposure period. Significant differences between Comet assay results in blood
      cells from animals exposed to tobacco leaves with and without pesticide were
      found in 24 and 48 h exposure periods in relation to negative control. Bone
      marrow cells from the group exposed to leaves with pesticide (48 h) also
      demonstrated significant increase in DNA damage. Concerning the micronucleus
      test, only animals exposed to tobacco leaves without pesticide (24 h) showed
      increase in frequency of micronuclei when compared to the negative control.
      Oxidative stress activities also were demonstrated for different groups. The
      results demonstrate the injury effect caused by tobacco leaves in different Mus
      musculus tissues, suggesting that the effects of dermal exposure to tobacco
      leaves are caused by complex mixtures present in the plant, but mainly by
      nicotine.

PMID- 20684554
TI  - In vitro digestion of beta-lactoglobulin fibrils formed by heat treatment at low
      pH.
AB  - Extensive studies have been done on beta-lactoglobulin (beta-Lg) fibrils in the
      past decade due to their potential as functional food ingredients, gelling
      agents, and encapsulation devices etc. (van der Goot, A. J.; Peighambardoust, S.
      H.; Akkermans, C.; van Oosten-Manski, J. M. Creating novel structures in food
      materials: The role of well-defined shear flow. Food Biophys. 2008, 3(2), 120-125
      and Loveday, S. M.; Rao, M. A.; Creamer, L. K.; Singh, H. Factors affecting
      rheological characteristics of fibril gels: The case of beta-lactoglobulin and
      alpha-lactalbumin. J. Food Sci. 2009, 74 (3), R47-R55). However, most of the
      studies focus on the formation and mechanism of the fibrils. Little is known
      about fibril digestibility to date. In this work, in vitro pepsin digestion of
      bovine beta-lactoglobulin (beta-Lg) fibrils in simulated gastric fluid was
      investigated using thioflavin T fluorescence photometry, sodium dodecyl sulfate
      polyacrylamide gel electrophoresis, size-exclusion chromatography, matrix
      assisted laser desorption/ionization mass spectrometry, and transmission electron
      microscopy (TEM). The fibrils were formed by heating beta-Lg solutions at 80
      degrees C and pH 2.0 for 20 h. The fibrils were found to be digested completely
      by pepsin within 2 min, when long, straight fibrils were no longer observed by
      TEM. The peptides in the fibrils (2000-8000 Da) could be digested to smaller
      peptides (mostly <2000 Da) by pepsin. The peptides in the fibrils were believed
      to be more susceptible for pepsin to access and attack because of their
      hydrophobic nature. For comparison purposes, solutions of beta-Lg heated at
      neutral pH (pH 7.4) were also studied under the same conditions.

PMID- 20684555
TI  - Optical properties of poly(ferrocenylsilane) multilayer thin films.
AB  - Spectroscopic ellipsometry has been used to investigate the optical properties of
      poly(ferrocenylsilane) polyion multilayer thin films in the visible and near
      infrared range of the spectrum. The thin films were deposited using the layer-by
      layer assembly process. Films with thicknesses of up to 55 nm were fabricated
      stepwise from polyelectrolyte solutions with a controlled ionic strength. These
      films allow an accurate characterization of the optical properties of
      poly(ferrocenylsilane) polyion layers. We show that the complex refractive index
      can be described by a simple Cauchy model. Refractive index values vary over the
      spectral range from 1.53 (near-infrared) to 1.8 (ultraviolet).

PMID- 20684556
TI  - Structurally informed site-directed mutagenesis of a stereochemically promiscuous
      aldolase to afford stereochemically complementary biocatalysts.
AB  - 2-Keto-3-deoxygluconate aldolase from the hyperthermophile Sulfolobus
      solfataricus is a highly thermostable type I aldolase that can catalyze carbon
      carbon bond formation using nonphosphorylated substrates. However, it exhibits
      poor diastereocontrol in many of its aldol reactions, including the reaction of
      its natural substrates, pyruvate and D-glyceraldehyde, which afford a 55:45
      mixture of D-2-keto-3-deoxygluconate (D-KDGlu) and D-2-keto-3-deoxy-galactonate
      (D-KDGal). We have employed detailed X-ray crystallographic structural
      information of this aldolase bound to these diastereoisomeric aldol products to
      selectively target specific amino acids for mutation for the rapid creation of
      stereochemically complementary mutants that catalyze either (Re)- or (Si)-facial
      selective aldol reactions to afford either D-KDGlu or D-KDGal with good levels of
      diastereocontrol.

PMID- 20684557
TI  - Enantioselective synthesis of trans-aryl- and -heteroaryl-substituted
      cyclopropylboronates by copper(I)-catalyzed reactions of allylic phosphates with
      a diboron derivative.
AB  - A new asymmetric route for the synthesis of trans-2-aryl- and -heteroaryl
      substituted cyclopropylboronates has been developed. (Z)-3-arylallylic phosphates
      were converted to the optically active products with high yield and diastereo-
      and enantioselectivity through a copper(I)-catalyzed reaction with a diboron
      derivative. Under mild reaction conditions, the reaction affords the
      arylcyclopropane products with a functional group and a heteroaromatic group in a
      highly enantioselective manner. When (E)-allylic phosphates were used as
      substrates, a ligand-controlled product switch between the trans and cis
      configurations was observed.

PMID- 20684558
TI  - Thermal oxidation for controlling protein interactions with porous silicon.
AB  - Thermal oxidation of porous silicon (pSi) has been used to control interactions
      with three proteins; lysozyme, papain, and human serum albumin (HSA) enabling the
      influences of protein structure, molecular weight, and charge to be elucidated.
      Adsorption behavior was assessed via adsorption isotherms while the structures of
      adsorbed proteins were investigated using a bioactivity assay, FTIR, and zeta
      potential. Time-of-flight secondary ion mass spectrometry was used to examine
      protein pore penetration. High protein adsorption onto unoxidized pSi (240-610
      microg/m(2)) was attributed to predominately hydrophobic interactions which
      resulted in structural changes of the adsorbed proteins and significant loss of
      bioactivity. Thermal oxidation at 400 and 800 degrees C significantly reduced
      protein adsorption (80-485 microg/m(2)) by reducing hydrophobicity. Oxidation of
      pSi modified the protein adsorption mechanisms to solely electrostatic attraction
      for positively charged proteins and structural rearrangement for negatively
      charged proteins. Adsorption via electrostatic attraction preserved protein
      bioactivity and zeta potential, thus inferring a retention of their native
      structure. In contrast, the negative charge and globular structure of HSA
      resulted in a loss of structure. We have demonstrated that thermal oxidation of
      pSi can be used to control protein interactions, adsorbed structure, and
      bioactivity.

PMID- 20684559
TI  - Netlike knitting of polyelectrolyte multilayers on honeycomb-patterned substrate.
AB  - The pH-amplified exponential growth layer-by-layer (LBL) self-assembly process
      was directly performed on honeycomb-patterned substrate for achievement of
      "guided patterning" of polyelectrolyte multilayers. Polyethylenimine (PEI) and
      poly(acrylic acid) (PAA) were used as polyanions, and their pH were carefully
      tuned to achieve pH-enhanced exponential growth. Guided by underlying hexagonally
      patterned islandlike poly(dimethylsiloxane) (PDMS) arrays, the diffusive
      polyelectrolytes rapidly interweaved into linear, multilayered structures
      distributed along the grooves between the patterned protuberate and formed a
      regular network of multilayered film with uniform mesh size. Netlike "knitting"
      of polyelectrolyte multilayers on honeycomb-patterned substrate has been realized
      by following this procedure. Superhydrophobic surfaces could be readily obtained
      after several bilayers of LBL assembly (with thermal cross-linking and surface
      fluorination by chemical vapor deposition), indicating that successful
      fabrication of functional micro- and nanoscale hierarchical structures can be
      achieved. Both high- and low-adhesion superhydrophobic surfaces ("petal effect"
      and "lotus effect") can be obtained with different bilayers of assembly, proving
      that different levels of nano- to microstructural hierarchy can be realized using
      this method. Furthermore, we were able to get topographically asymmetric, free
      standing, polyelectrolyte multilayer films in the case that we performed more
      than eight bilayers of assembly. This research reported template-directed LBL
      patterning assembly for the first time. It provides a beneficial exploration for
      the surface patterning technique for the LBL assembly process.

PMID- 20684560
TI  - Radical redesign of a tandem array of four R67 dihydrofolate reductase genes
      yields a functional, folded protein possessing 45 substitutions.
AB  - R67 dihydrofolate reductase (DHFR) is a plasmid-encoded, type II enzyme. Four
      monomers (78 amino acids long) assemble into a homotetramer possessing 222
      symmetry. In previous studies, a tandem array of four R67 DHFR gene copies was
      fused in frame to generate a functional monomer named Quad1. This protein
      possessed the essential tertiary structure of the R67 "parent". To facilitate
      mutagenesis reactions, restriction enzyme sites were introduced in the tandem
      gene array. S59A and H362L mutations were also added to minimize possible folding
      topologies; this protein product, named Quad3, possesses 10 substitutions and is
      functional. Since R67 DHFR possesses a stable scaffold, a large jump in sequence
      space was performed by the further addition of 45 amino acid substitutions. The
      mutational design utilized alternate sequences from other type II DHFRs. In
      addition, most of the mutations were positioned on the surface of the protein as
      well as in the disordered N-terminal sequence, which serves as the linker between
      the fused domains. The resulting Quad4 protein is quite functional; however, it
      is less stable than Quad1, suffering a DeltaDeltaG loss of 5 kcal/mol at pH 5.
      One unexpected result was formation of Quad4 dimers and higher order oligomers at
      pH 8. R67 DHFR, and its derivative Quad proteins, possesses a robust scaffold,
      capable of withstanding introduction of >or=55 substitutions.

PMID- 20684561
TI  - Chemical modification of the Rieske protein from Thermus thermophilus using
      diethyl pyrocarbonate modifies ligating histidine 154 and reduces the [2FE-2S]
      cluster.
AB  - Rieske proteins are a class of electron transport proteins that are intricately
      involved in respiratory and photosynthetic processes. One unique property of
      Rieske proteins is that the reduction potential is pH-dependent. The ionizable
      groups responding to changes in pH have recently been shown to be the two
      histidine residues that ligate the [2Fe-2S] cluster. To probe the chemical
      reactivity toward and the accessibility of the ligating histidines to small
      molecules, akin to the substrate quinol and the inhibitor stigmatellin, the
      Thermus thermophilus Rieske protein was reacted with diethyl pyrocarbonate (DEPC)
      over a range of pH values. The modification was followed by UV-visible, circular
      dichroism, and EPR spectroscopies and the end product analyzed by mass
      spectrometry. The ligating His154, as well as the two nonligating histidines and
      surface-exposed lysines, were modified. Interestingly, modification of the
      protein by DEPC was also found to reduce the metal cluster. The ability to
      control the redox state was examined by the addition of oxidants and reductants
      and removal of the DEPC-histidine adduct by sodium hydroxide. Characterization of
      the DEPC-modified Rieske protein, which remains redox active, offers a probe to
      analyze the effects of small molecules that inhibit the function of the bc(1)
      complex and that have also been shown to interact with the ligating histidines of
      the Rieske [2Fe-2S] cluster in crystal structures of the complex.

PMID- 20684563
TI  - Discovery of N-{1-[3-(3-oxo-2,3-dihydrobenzo[1,4]oxazin-4-yl)propyl]piperidin-4
      yl}-2-phenylacetamide (Lu AE51090): an allosteric muscarinic M1 receptor agonist
      with unprecedented selectivity and procognitive potential.
AB  - The discovery and structure-activity relationship (SAR) of a series of allosteric
      muscarinic M(1) receptor agonists are described. Compound 17 (Lu AE51090) was
      identified as a representative compound from the series, based on its high
      selectivity as an agonist at the muscarinic M(1) receptor across a panel of
      muscarinic receptor subtypes. Furthermore, 17 displayed a high degree of
      selectivity when tested in a broad panel of G-protein-coupled receptors, ion
      channels, transporters, and enzymes, and 17 showed an acceptable pharmacokinetic
      profile and sufficient brain exposure in rodents in order to characterize the
      compound in vivo. Hence, in a rodent model of learning and memory, 17 reversed
      delay-induced natural forgetting, suggesting a procognitive potential of 17.

PMID- 20684562
TI  - Synthesis, structure-activity relationship, and mode-of-action studies of
      antimalarial reversed chloroquine compounds.
AB  - We have previously shown that a "reversed chloroquine (RCQ)" molecule, composed
      of a chloroquine-like moiety and a resistance reversal-like moiety, can overcome
      chloroquine resistance in P. falciparum ( Burgess , S. J. ; Selzer , A. ; Kelly ,
      J. X. ; Smilkstein , M. J. ; Riscoe , M. K. ; Peyton , D. H. J. Med. Chem. 2006 ,
      49 , 5623 . Andrews , S. ; Burgess , S. J. ; Skaalrud , D. ; Kelly , J. X. ;
      Peyton , D. H. J. Med. Chem. 2010 , 53 , 916 ). Here, we present an investigation
      into the structure-activity relationship of the RCQ structures, resulting in an
      orally active molecule with good in vitro and in vivo antimalarial activity. We
      also present evidence of the mode of action, indicating that the RCQ molecules
      inhibit hemozoin formation in the parasite's digestive vacuole in a manner
      similar to that of chloroquine.

PMID- 20684564
TI  - Mild and general zinc-alkoxide-catalyzed allylations of ketones with allyl
      pinacol boronates.
AB  - A general and efficient zinc-alkoxide-catalyzed allylation of a diverse array of
      ketones with allyl boronates is presented. The methodology is effective with 2
      mol % of catalyst and with relatively short reaction times. Studies of the key
      exchange process are presented, which support a cyclic transition state for the
      boron to zinc exchange.

PMID- 20684565
TI  - Variation of ion polarizability from vacuum to hydration: insights from Hirshfeld
      partitioning.
AB  - The results of iterative Hirshfeld partitioning on the polarizability of
      monovalent anions (F(-), Cl(-), and Br(-)) and Na(+) in water clusters ranging
      from n = 0 to n = 25 are presented. In each case, the ions reach a limiting
      intrinsic polarizability in the fully hydrated state. For F(-), Cl(-), and Br(-)
      using B3LYP/aug-cc-pVDZ, the intrinsic polarizabilities in the condensed-phase
      limit are 47.2 +/- 0.7%, 47.2 +/- 0.3%, and 54.2 +/- 0.4% of their gas-phase
      value at the corresponding level of theory. The extent of this scaling depends on
      the basis set (we also consider B3LYP/aug-cc-pVTZ), but intrinsic
      polarizabilities are generally within 35-55% of the gas-phase value. The sodium
      cation is the least polarizable in the condensed-phase limit. The average
      intrinsic polarizability of water in these clusters decreases with the size of
      the cluster, which is consistent with earlier Hirshfeld analysis of intrinsic
      polarizabilities of pure water (Krishtal, A.; Senet, P.; Yang, M.; van Alsenoy,
      C. J. Chem. Phys. 2006, 125, 034312). Further analysis demonstrates that water
      molecules near ions in sufficiently large clusters (n = 25) have intrinsic
      polarizabilities similar to those of water molecules fully coordinated in a pure
      aqueous cluster. The observed binodal distribution of the water intrinsic
      polarizability within the cluster is attributed to polarizability differences
      between interior and exterior water molecules. This observation is in qualitative
      agreement with arguments based on Pauli's exclusion principle that suggest a
      reduced polarizability for condensed-phase water relative to the vacuum value.

PMID- 20684566
TI  - Enthalpic efficiency of ligand binding.
AB  - The thermodynamics of ligand-protein binding has received much attention
      recently. In the present contribution we focus on the enthalpic component of
      binding. The dissociation constant, pK(d), was decomposed into enthalpic and
      entropic components (pK(d) = pK(H) + pK(S)), and pK(H), defined as pK(H) = 
      DeltaH/(2.303.RT) was used to characterize the enthalpy contribution to binding.
      It was found that the maximal achievable pK(H) decreases with increasing
      molecular size. This is in contrast to maximal pK(d) that increases with
      molecular size until it achieves a plateau. Size-independent enthalpic efficiency
      (SIHE) was defined as SIHE = pK(H)/40.HA(0.3), with HA being the number of heavy
      atoms. SIHE allows a size unbiased comparative binding characterization of
      compounds. It can find use in hit and lead selection and also in monitoring
      optimization in drug discovery programs. The physical background of decreasing
      maximal pK(H) with molecular size is discussed, and its consequences to drug
      discovery are analyzed. It is concluded that the feasibility of simultaneous
      optimization of affinity and enthalpy diminishes with increasing molecular size.
      Consequently, binding thermodynamics considerations are to be applied primarily
      in hit prioritization and hit-to-lead optimization.

PMID- 20684567
TI  - Novel carbamates as orally active acetylcholinesterase inhibitors found to
      improve scopolamine-induced cognition impairment: pharmacophore-based virtual
      screening, synthesis, and pharmacology.
AB  - A systematic virtual screening (VS) experiment, consisting of the development of
      3D-pharmacophore, screening of virtual library, synthesis, and pharmacology, is
      reported. The predictive pharmacophore model (correlation = 0.955) with one H
      bond donor and three hydrophobic features was developed using HypoGen on a
      training set of 24 carbamates as AChE inhibitors. The model was validated on a
      test set of 40 carbamates (correlation = 0.844). The pharmacophore-based VS of
      virtual library led to the identification of novel carbamates as potent AChE
      inhibitors. The synthesis and pharmacological evaluation of nine carbamates
      against three diverse assay systems, namely (i) in vitro Ellman method, (ii) in
      vivo passive avoidance test, and (iii) aldicarb-sensitivity assay, led to the
      discovery of orally active novel AChE inhibitors which improved scopolamine
      induce cognition impairment in Swiss male mice. Finally, two novel lead compounds
      85 and 86 are selected as candidate molecules for further optimization.

PMID- 20684568
TI  - Targeted in-gel MRM: a hypothesis driven approach for colorectal cancer biomarker
      discovery in human feces.
AB  - Colorectal cancer (CRC) is the second most common cause of cancer-related deaths
      in both men and women. The fecal occult blood test is currently the first line
      method for CRC screening but has an unacceptably low sensitivity and specificity.
      Improved screening tests are therefore urgently required for early stage CRC
      screening. We have described a hypothesis-driven approach for a rapid biomarker
      discovery process whereby selected proteins previously implicated as colorectal
      cancer-associated proteins (CCAP), which can potentially be shed into the feces
      from a colorectal tumor, are targeted for excision from 1D-SDS-PAGE based on
      their predicted molecular weight followed by directed identification and relative
      quantification using multiple reaction monitoring (MRM). This approach can
      significantly reduce the time for clinical assay development with the added
      advantage that many proteins will have been validated by previous in vitro and/or
      in vivo studies. Sixty potential CCAPs were selected from the literature and
      appropriate MRM conditions were established for measurement of proteotypic
      peptides. Nineteen of these proteins were detected in the feces from a patient
      with colorectal cancer. Relative quantitation of these 19 CCAP across 5 CRC
      patients and 5 healthy volunteers were carried out, revealing hemoglobin,
      myeloperoxidase, S100A9, filamin A and l-plastin to be present only in the feces
      of CRC patients.

PMID- 20684569
TI  - Hydrolyzable aromatic copolyesters of p-dioxanone.
AB  - Entropically driven ring-opening copolymerization of mixtures of a fraction of
      cyclic oligo(hexamethylene terephthalate)s composed of cycle sizes from 2 to 5
      and p-dioxanone was used to prepare random copolyesters covering a range of
      aromatic (HT) to aliphatic (DO) units ratios from 9 to 1.3. The composition and
      microstructure of the copolyesters were accurately determined by (1)H and (13)C
      NMR, respectively. The copolyesters showed thermal degradation and glass
      transition temperatures in good agreement with their comonomeric composition and
      microstructure, and they crystallized for contents in DO less than 30%, adopting
      the same crystal structure as poly(hexamethylene terephthalate). The copolyesters
      appeared to be sensitive to hydrolytic degradation, which was observed to take
      place superficially with the generation of non-water-soluble degraded fragments
      and with the release of water-soluble dioxanoic acid to the aqueous medium.

PMID- 20684570
TI  - Nanoparticles of conjugated polymers.

PMID- 20684571
TI  - Dehydration, dehydroxylation, and rehydroxylation of single-walled
      aluminosilicate nanotubes.
AB  - Single-walled metal oxide (aluminosilicate) nanotubes are excellent candidates
      for addressing the long-standing issue of functionalizing nanotube interiors, due
      to their high surface reactivity and controllable dimensions. However,
      functionalization of the nanotube interior is impeded by its high surface silanol
      density (9.1 -OH/nm(2)) and resulting hydrophilicity. Controlled dehydration of
      the nanotubes is critical for the success of functionalization efforts. We employ
      a range of solid-state characterization tools to elucidate dehydration and
      dehydroxylation phenomena in the nanotubes as a function of heat treatment up to
      450 degrees C. Vibrational spectroscopy (Fourier transform infrared, FT-IR),
      thermogravimetric analysis-mass spectrometry (TGA-MS), nitrogen physisorption,
      solid-state NMR, and X-ray diffraction (XRD) reveal that a completely dehydrated
      condition is achieved at 250 degrees C under vacuum and that the maximum pore
      volume is achieved at 300 degrees C under vacuum due to partial dehydroxylation
      of the dehydrated nanotube. Beyond 300 degrees C, further dehydroxylation
      partially disorders the nanotube wall structure. However, a unique
      rehydroxylation mechanism can partially reverse these structural changes upon re
      exposure to water vapor. Finally, detailed XRD simulations and experiments allow
      further insight into the nanotube packing, the dimensions, and the dependence of
      nanotube XRD patterns on the water content.

PMID- 20684572
TI  - van der Waals interactions between nanotubes and nanoparticles for controlled
      assembly of composite nanostructures.
AB  - We have demonstrated that ubiquitous van der Waals forces are significant in
      controlling the interactions between nanoparticles and nanotubes. The adsorption
      of gold nanoparticles (AuNPs) on nanotubes (MWNTs) obeys a simple quadratic
      dependence on the nanotube surface area, regardless of the source of AuNPs and
      MWNTs. Changes in the geometric parameters of the components have pronounced
      effects on the affinity of nanoparticles for nanotubes, with larger, more
      polarizable nanostructures exhibiting stronger attractive interactions, the
      impact of which changes in the following order MWNT diameter > AuNP diameter >
      MWNT length.

PMID- 20684573
TI  - Ab initio calculations on the electronically excited states of small helium
      clusters.
AB  - The vertical excitation energies of small helium clusters, He(7) and He(25), have
      been calculated using configuration interaction singles, and the character of the
      excited states was determined using attachment/detachment density analysis. It
      was found that in the n = 2 manifold the excitations could be interpreted as
      superpositions of atomic states, with excitations on the surface of the clusters
      being lower in energy than those in the bulk. For the n = 2 excited states with
      significant density on the interior of the cluster, mixing with the atomic n = 3
      states resulted in lower excitation energies. For the n = 3 states the spatial
      extent of the excited-state density can be much larger than the size of the
      cluster, making analysis of the states more difficult and highly dependent on the
      internuclear distance. Introducing disorder into the clusters results in some
      localization of the excited states, although highly delocalized states are always
      observed in these small clusters. In addition, experimental results for small
      clusters are interpreted in terms of these findings.

PMID- 20684574
TI  - A computational fluid dynamics approach to nucleation in the water-sulfuric acid
      system.
AB  - This study presents a computational fluid dynamics modeling approach to
      investigate the nucleation in the water-sulfuric acid system in a flow tube. On
      the basis of an existing experimental setup (Brus, D.; Hyvarinen, A.-P.;
      Viisanen, Y.; Kulmala, M.; Lihavainen, H. Atmos. Chem. Phys. 2010, 10, 2631
      2641), we first establish the effect of convection on the flow profile. We then
      proceed to simulate nucleation for relative humidities of 10, 30, and 50% and for
      sulfuric acid concentration between 10(9) to 3 x 10(10) cm(-3). We describe the
      nucleation zone in detail and determine how flow rate and relative humidity
      affect its characteristics. Experimental nucleation rates are compared to rates
      gained from classical binary and kinetic nucleation theory as well as cluster
      activation theory. For low RH values, kinetic theory yields the best agreement
      with experimental results while binary nucleation best reproduces the
      experimental nucleation behavior at 50% relative humidity. Particle growth is
      modeled for an example case at 50% relative humidity. The final simulated
      diameter is very close to the experimental result.

PMID- 20684575
TI  - Vacuum-ultraviolet negative photoion spectroscopy of SF5Cl.
AB  - With use of vacuum-UV radiation from a synchrotron, gas-phase negative ions are
      detected by mass spectrometry following photoexcitation of SF(5)Cl. F(-), Cl(-),
      and SF(5)(-) are observed, and their ion yields recorded in the range 8-30 eV. F(
      ) and Cl(-) show a linear dependence of signal with pressure, showing that they
      arise from unimolecular ion-pair dissociation, generically written AB + h nu -->
      C(-) + D(+) (+ neutral(s)). F(-) is the strongest signal, and absolute cross
      sections are determined by calibrating the signal intensity with that of F(-)
      from SF(6) and CF(4). Resonances are observed and assigned to transitions to
      Rydberg states of SF(5)Cl. The Cl(-) signal is much weaker, despite the S-Cl bond
      being significantly weaker than the S-F bond. Appearance energies for F(-) and
      Cl(-) of 12.7 +/- 0.2 and 10.6 +/- 0.2 eV are determined. The spectra suggest
      that these ions form indirectly by crossing of Rydberg states of SF(5)Cl onto an
      ion-pair continuum.

PMID- 20684576
TI  - Study of the photodissociation process of ClC(O)SCH3 using both synchrotron
      radiation and HeI photoelectron spectroscopy in the valence region.
AB  - The simultaneous evaluation of the PES and valence synchrotron photoionization
      studies complemented by the results of quantum chemical calculations offers
      unusually detailed insights into the valence ionization processes of small
      covalent molecules. Thus, methyl thiochloroformate, ClC(O)SCH(3), has been
      investigated by using results from both photoelectron spectroscopy (PES) and
      synchrotron radiation in the valence energy range. In an additional series of
      experiments, total ion yield (TIY) and photoelectron-photoion coincidence
      (PEPICO) spectra have been recorded. Furthermore, the relative yields for ionic
      fragments have been determined as a function of the photon energy. Vibronic
      structure has been observed in the TIY spectrum recorded in the synchrotron
      experiments. The photodissociation behavior of ClC(O)SCH(3) can be divided into
      two well-defined energy regions.

PMID- 20684577
TI  - Infrared spectra of CX2=CoX2 and CX3-CoX complexes from reactions of laser
      ablated cobalt atoms with halomethanes.
AB  - Simple cobalt complexes with substantial carbon-cobalt double bond character are
      produced in Co atom reactions with tetra-, tri-, and dihalomethanes, whereas
      insertion complexes are identified only in the dihalomethane matrix infrared
      spectra. These complexes are identified from matrix infrared spectra and
      comparison with frequencies computed by density functional theory. Exclusive
      generation of carbenes in the tetrahalomethane systems is consistent with the
      computational results that the staggered allene-type conformer is the only
      meaningful energy minimum in the reaction path. Their short C-Co bondlengths of
      1.732-1.764 A and CASSCF computed bond orders near 1.7 are also appropriate for
      carbon-cobalt double bonds. Hence, reactions of laser-ablated Co atoms are
      effective means to generate rarely reported high oxidation-state Co complexes
      with carbon-cobalt double bonds. Unlike the Rh and Ir cases, Co carbynes (with C
      Co triple bonds) are not formed. The observation of CH(2)Cl-CoF with
      photoreversible intensity variation in the spectra provides unique insight on
      halogen migration from interconversion with CH(2)F-CoCl through the CH(2)=CoFCl
      carbene.

PMID- 20684578
TI  - Formation and decay of fluorobenzene radical anions affected by their isomeric
      structures and the number of fluorine atoms.
AB  - Aryl fluoride has attracted much attention as a resist component for extreme
      ultraviolet (EUV) lithography, because of the high absorption cross section of
      fluorine for EUV photons; however, less is known about electron attachment to
      fluorobenzene (FBz) and the stability of the reduced state. Picosecond and
      nanosecond pulse radiolysis of tetrahydrofuran solutions of FBz from mono-, di-,
      tri-, tetra-, penta-, and hexafluorobenzene was performed, and the effects of
      isomeric structure and number of fluorine atoms were examined. Scavenging of
      solvated electrons was found to correlate with the electron affinity obtained by
      density functional theory in the gas phase, whereas the decay of FBz radical
      anions was dominated by the activation energy of fluorine anion dissociation
      calculated using a polarized continuum model (PCM). A sharp contrast in the
      lifetimes of ortho-, meta-, and para-position difluorobenzene was observed, which
      could provide information on the molecular design of functional materials.

PMID- 20684579
TI  - Excited-state intermolecular proton transfer of the firefly's chromophore D
      luciferin.
AB  - Steady-state absorption and emission as well as time-resolved emission
      spectroscopies were employed to study the photophysics and photochemistry of D
      luciferin, the firefly active bioluminescent compound. In aqueous solution the
      electronically excited-state protonated D-luciferin compound undergoes an
      efficient process of proton transfer to the solvent, with a rate constant k(PT) =
      3.0 x 10(10) s(-1). We found a kinetic isotope effect of about 2.5 for this
      process. The deprotonated form of D-luciferin in the excited state recombines
      irreversibly with the geminate proton. Hence, the fluorescence decay of the
      deprotonated form is nonexponential, and the fluorescence quantum yield is low.

PMID- 20684580
TI  - Tantalum dioxide complexes with dinitrogen. formation and characterization of the
      side-on and end-on bonded TaO2(NN)x (x = 1-3) complexes.
AB  - The reaction of tantalum dioxide molecule with dinitrogen has been studied by
      matrix isolation infrared spectroscopy. The tantalum dioxide molecules produced
      from laser evaporation of bulk Ta(2)O(5) target reacted with dinitrogen to form
      the TaO(2)(eta(1)-NN)(x) (x = 1-3) complexes on annealing, in which the N(2)
      ligands are end-on bonded to the tantalum metal center. The TaO(2)(eta(1)-NN)(3)
      complex decomposed to TaO(2)(eta(1)-NN)(2) under infrared irradiation. The
      TaO(2)(eta(1)-NN)(2) and TaO(2)(eta(1)-NN)(3) complexes rearranged to the less
      stable TaO(2)(eta(1)-NN)(eta(2)-N(2)) and TaO(2)((eta(1)-NN)(2)(eta(2)-N(2))
      isomers under visible light excitation. Both the mono- and bis-dinitrogen
      complexes were predicted to have (2)A' or (2)A(1) ground states arising from the
      (2)A(1) ground state of TaO(2), whereas the two tridinitrogen complexes were
      predicted to have (2)B(2) ground states with C(2v) symmetry, which are derived
      from the (2)B(1) excited state of TaO(2).

PMID- 20684581
TI  - Infrared spectroscopy of (HCl)m(H(2)O)n clusters in helium nanodroplets:
      definitive assignments in the HCl stretch region.
AB  - Infrared spectra in the HCl stretch region (2600-2900 cm(-1)) are presented for
      small, mixed (HCl)(m)(H(2)O)(n) clusters solvated in helium nanodroplets. Sharp
      bands associated with the Cl-H...Cl stretch vibrations in m:n = 1:1, 2:1, 2:2,
      and 3:1 clusters are superimposed on a broad background that increases in
      intensity as larger clusters are grown within the droplets. The broad background
      is determined to be partially due to mixed clusters with m > 3 and n > 2. The
      sharp bands are assigned to specific cluster compositions, m:n, via pick-up
      pressure dependence studies and optically selected mass spectrometry. Orientation
      of the clusters is achieved with the application of a large electric field to the
      laser/droplet beam interaction region. The intensity of each band is measured as
      a function of the applied field strength. Simulations of this electric field
      dependence based on ab initio calculations of permanent dipole moments and
      vibrational transition moment angles leads to definitive structural assignments
      for each sharp band. The 2:1 complex is cyclic, and a band associated with the
      2:2 cluster is determined to arise from the nonalternating cyclic structure.

PMID- 20684582
TI  - Phase diagram of hexahydro-1,3,5-trinitro-1,3,5-triazine crystals at high
      pressures and temperatures.
AB  - Raman spectroscopy and optical imaging were used to determine the phase
      boundaries between various hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX)
      polymorphs. Experiments were performed on single crystals at pressures up to 8.0
      GPa and temperatures ranging from room temperature to 550 K. Several distinct
      pressure regions were found in the RDX response at elevated temperatures: (i)
      melting of alpha-RDX followed by decomposition, below 2.0 GPa, (ii) decomposition
      of alpha-RDX between 2.0 and 2.8 GPa, (iii) irreversible transformation of alpha-
      and gamma-RDX to epsilon-RDX between 2.8 and 6.0 GPa, and (iv) decomposition of
      gamma-RDX above 6.0 GPa. A triple point between the alpha-, gamma-, and epsilon
      RDX was found at 3.7 GPa and 466 K. The alpha-gamma phase transition was
      confirmed to occur at the same pressure, approximately 3.7 GPa, regardless of
      temperature, in the range of 295-460 K. Furthermore, it was determined that
      epsilon-RDX (i) has limited chemical stability under the pressure and temperature
      conditions where it is produced and (ii) decomposes according to the
      autocatalytic rate law. The findings reported here have provided new information
      about the response of RDX crystals at high pressures and temperatures.

PMID- 20684583
TI  - Kinetics and products of the acid-catalyzed ring-opening of atmospherically
      relevant butyl epoxy alcohols.
AB  - Epoxydiols are produced in the gas phase from the photo-oxidation of isoprene in
      the absence of significant mixing ratios of nitrogen oxides (NO(x)). The reactive
      uptake of these compounds onto acidic aerosols has been shown to produce
      secondary organic aerosol (SOA). To better characterize the fate of isoprene
      epoxydiols in the aerosol phase, the kinetics and products of the acid-catalyzed
      ring-opening reactions of four hydroxy-substituted epoxides were studied by
      nuclear magnetic resonance (NMR) techniques. Polyols and sulfate esters are
      observed from the ring-opening of the epoxides in solutions of
      H(2)SO(4)/Na(2)SO(4). Likewise, polyols and nitrate esters are produced in
      solutions of HNO(3)/NaNO(3). In sulfuric acid, the rate of acid-catalyzed ring
      opening is dependent on hydronium ion activity, sulfate ion, and bisulfate. The
      rates are much slower than the nonhydroxylated equivalent epoxides; however, the
      hydroxyl groups make them much more water-soluble. A model was constructed with
      the major channels for epoxydiol loss (i.e., aerosol-phase ring-opening, gas
      phase oxidation, and deposition). In the atmosphere, SOA formation from
      epoxydiols will depend on a number of variables (e.g., pH and aerosol water
      content) with the yield of ring-opening products varying from less than 1% to
      greater than 50%.

PMID- 20684584
TI  - Conformational analysis of 2,2'-bithiophene revisited: the maximum entropy method
      applied to large sets of H-H and 13C-H partially averaged dipolar couplings.
AB  - Two recently determined sets of partially averaged H-H and (13)C-H NMR dipolar
      couplings of 2,2'-bithiophene as a solute in nematic liquid-crystalline solvents
      have been analyzed by means of the maximum entropy method. This investigation
      originated to ascertain the real information content of the new (13)C-H data. To
      this end, a procedure has been employed which consists in adding the experimental
      data one after the other and monitoring, during each of these steps, the behavior
      of the minimum of the associated work function as well as that of the root-mean
      square deviation. It turns out that nearly all (13)C-H data do not provide new
      pieces of information with respect to a subset of seven H-H dipolar couplings.
      Inclusion of the very few which do, however, alters significantly the
      conformational distribution function calculated taking into account the sole H-H
      dipolar couplings. The final form of this function is characterized by a
      prominent peak corresponding to the trans conformation and two smaller peaks
      corresponding to the cis conformation and of the conformation in which the two
      rings are mutually orthogonal. The form of the conformational distribution
      function is the result of a considerable orientational-conformational coupling.
      The implications of the present results on the form of the torsional potential
      energy function of the isolated molecule are discussed.

PMID- 20684585
TI  - Ground and low-lying excited electronic states of [3,3'] bidiazirinylidene
      (C2N4).
AB  - The second-order generalized Van Vleck perturbation theory (GVVPT2) variant of
      multireference perturbation theory was used to investigate the ground and low
      lying excited electronic states of [3,3'] bidiazirinylidene (C(2)N(4)). C(2)N(4)
      is arguably the simplest molecule with multiple CN(2) rings. Equilibrium
      geometries and adiabatic energy differences of the 1(1)A(g) ground state and 2
      (1)A(g), 1(1)B(1g), 1(3)B(1g), 1(1)B(2g), 1(3)B(2g), 1(1)B(3g), 1(3)B(3g),
      1(1)B(2u), 1(3)B(2u), 1(1)B(3u), and 1(3)B(3u) excited states of D(2h) symmetry
      were obtained. In addition, vertical excitation energies to and emission energies
      from the excited states were obtained. The 1(1)A(g) optimized geometry and
      harmonic frequencies for the CN(2) rings in C(2)N(4) are similar to those for the
      related difluorodiazirine molecule: R(CN), R(NN) bonds and the angleNCN angle are
      0.012 and 0.006 A longer and 0.8 degrees smaller than that for the ring in
      F(2)CN(2). The NN stretch frequencies are 1470 and 1562 cm(-1), and CN stretches
      are 993 and 995 cm(-1). The similarity between the GVVPT2 results of C(2)N(4) and
      F(2)CN(2) suggests that C(2)N(4) might be sufficiently stable to be synthesized.
      The lowest-energy spin- and electric dipole-allowed vertical excitation, to the
      1(1)B(2u) state, is predicted to occur in the visible (2.30 eV, 538.9 nm).

PMID- 20684586
TI  - An efficient implementation of the generalized energy-based fragmentation
      approach for general large molecules.
AB  - An efficient implementation of the generalized energy-based fragmentation (GEBF)
      approach (Li, W.; Li, S.; Jiang, Y. J Phys. Chem. A 2007, 111, 2193) for treating
      a wide range of large molecules is presented. In this implementation, the
      fragmentation process can be automatically done for a general molecule, with only
      some functional groups defined by users. A new and fast scheme is designed for
      the generation of various subsystems and the derivation of their coefficients.
      The newly implemented GEBF approach has been applied to several large molecules
      including proteins, nucleic acids, and supermolecules with fused aromatic rings.
      Test calculations within the Hartree-Fock (HF) and density functional theory
      (DFT) framework demonstrate that the GEBF approach can provide reasonably
      accurate ground-state energies and optimized structures, which are in good
      agreement with those from conventional HF or DFT calculations. The GEBF approach
      implemented in this work can now be employed by nonexpert users to compute
      energies, optimized structures, and some molecular properties at various ab
      initio levels for a broad range of large molecules on ordinary PC workstations.

PMID- 20684587
TI  - Ping-pong at gold: proton jump between coordinated phenyl and eta1-benzene
      ligands, a computational study.
AB  - A DFT computational investigation predicts that the Au(III) complex
      (bpy)Au(C(6)H(5))(2+) reacts with benzene to furnish square planar
      (bpy)Au(C(6)H(5))(eta(1)-C(6)H(6))(2+). Intramolecular processes that occur
      within this species have been located, and the energetics of all processes have
      been quantified. The dynamic processes that have been identified are (1) benzene
      ring rotation with respect to Au, (2) direct hydrogen transfer from the benzene
      to the phenyl ligand, (3) hydrogen transfer from the ipso to the ortho positions
      in the coordinated benzene ligand, and (4) hydrogen transfer from the benzenium
      ligand formed by the ipso/ortho isomerization to the phenyl ligand. Similarities
      and differences are seen between the behavior of (bpy)Au(C(6)H(5))(eta(1)
      C(6)H(6))(2+) and previously reported isoelectronic Pt(II) complexes. Preliminary
      experimental results related to this chemistry are reported, and possible
      consequences for C-H bond activation mediated by gold are discussed.

PMID- 20684588
TI  - Triple-decker sandwiches and related compounds of the first-row transition metals
      containing cyclopentadienyl and benzene rings.
AB  - The triple-decker sandwich compound trans-Cp(2)V(2)(eta(6):eta(6)-mu-C(6)H(6))
      has been synthesized, as well as "slipped" sandwich compounds of the type trans
      Cp(2)Co(2)(eta(4):eta(4)-mu-arene) and the cis-Cp(2)Fe(2)(eta(4):eta(4)-mu
      C(6)R(6)) derivatives with an Fe-Fe bond (Cp = eta(5)-cyclopentadienyl).
      Theoretical studies show that the symmetrical triple-decker sandwich structures
      trans-Cp(2)M(2)(eta(6):eta(6)-mu-C(6)H(6)) are the global minima for M = Ti, V,
      and Mn but lie approximately 10 kcal/mol above the global minimum for M = Cr. The
      nonbonding M...M distances and spin states in these triple decker sandwich
      compounds can be related to the occupancies of the frontier bonding molecular
      orbitals. The global minimum for the chromium derivative is a singlet spin state
      cis-Cp(2)Cr(2)(eta(4):eta(4)-mu-C(6)H(6)) structure with a very short CrCr
      distance of 2.06 A, suggesting a formal quadruple bond. A triplet state cis
      Cp(2)Cr(2)(eta(4):eta(4)-mu-C(6)H(6)) structure with a predicted Cr[triple
      bond]Cr distance of 2.26 A lies only approximately 3 kcal/mol above this global
      minimum. For the later transition metals the global minima are predicted to be
      cis-Cp(2)M(2)(eta(6):eta(6)-mu-C(6)H(6)) structures with a metal-metal bond,
      rather than triple decker sandwiches. These include singlet cis
      Cp(2)Fe(2)(eta(4):eta(4)-mu-C(6)H(6)) with a predicted Fe=Fe double bond distance
      of 2.43 A, singlet cis-Cp(2)Co(2)(eta(3):eta(3)-mu-C(6)H(6)) with a predicted Co
      Co single bond distance of 2.59 A, and triplet cis-Cp(2)Ni(2)(eta(3):eta(3)-mu
      C(6)H(6)) with a predicted Ni-Ni distance of 2.71 A.

PMID- 20684589
TI  - Stability of lithium superoxide LiO2 in the gas phase: computational study of
      dimerization and disproportionation reactions.
AB  - Knowledge of the precise molecular mechanisms during the discharge and recharge
      processes in the lithium-air battery is critical for achieving desired
      improvements in specific capacity, current density, and cyclability. The initial
      oxygen reduction product formed in the presence of Li(+) ions is lithium
      superoxide LiO(2). In this study, we report the computed structures and
      thermodynamic parameters of LiO(2) dimerization in the gas phase, which enables
      us to provide a baseline for the reaction free energy profile of the subsequent
      disproportionation of (LiO(2))(2) to lithium peroxide Li(2)O(2) and O(2). Our
      calculations identified several low-lying (LiO(2))(2) dimers, with the singlet
      bipyramidal structure giving IR bands that are consistent with the characteristic
      IR vibration frequencies of (LiO(2))(2) in the oxygen matrix at T = 15-40 K. The
      activation barrier for (LiO(2))(2) = Li(2)O(2)+O(2) is 10.9 kcal/mol at the
      UCCSD(T)/CBS level (T = 298 K), suggesting that in the gas phase LiO(2) and its
      aggregates could only be observed at low temperatures.

PMID- 20684590
TI  - Anticooperative effect induced by mixed solvation in H+ (CH3OH)m(H2O)n (m + n = 5
      and 6): a theoretical and infrared spectroscopic study.
AB  - When a solvent molecule is replaced by another molecule with larger proton
      affinity, the strength of all other hydrogen bonds decreases. This is the concept
      of anticooperativity by successive substitution in a mixed solvation system. In
      the present study, this concept is demonstrated in H(+)(CH(3)OH)(m)(H(2)O)(n) (m
      + n = 5 and 6) mixed clusters by a joint theoretical and infrared (IR)
      spectroscopic approach. The observed IR spectra of the mixed clusters exhibit two
      high-frequency shifts of hydrogen-bonded OH stretch bands with increasing
      methanol content. These trends are well reproduced by first-principle IR spectra
      simulated by thermal averaging over a set of configurational isomers under the
      quantum harmonic superposition approach. Theoretical analysis on the magnitude of
      charge transfer from the protonated site to the solvent molecules is found to be
      in agreement with the spectroscopic measurement that the individual hydrogen bond
      in the mixed clusters is weakened with an increase of the mixing ratio of
      methanol to water.

PMID- 20684591
TI  - Identification of orally available naphthyridine protein kinase D inhibitors.
AB  - A novel 2,6-naphthyridine was identified by high throughput screen (HTS) as a
      dual protein kinase C/D (PKC/PKD) inhibitor. PKD inhibition in the heart was
      proposed as a potential antihypertrophic mechanism with application as a heart
      failure therapy. As PKC was previously identified as the immediate upstream
      activator of PKD, PKD vs PKC selectivity was essential to understand the effect
      of PKD inhibition in models of cardiac hypertrophy and heart failure. The present
      study describes the modification of the HTS hit to a series of prototype pan-PKD
      inhibitors with routine 1000-fold PKD vs PKC selectivity. Example compounds
      inhibited PKD activity in vitro, in cells, and in vivo following oral
      administration. Their effects on heart morphology and function are discussed
      herein.

PMID- 20684592
TI  - Identification of potent and selective amidobipyridyl inhibitors of protein
      kinase D.
AB  - The synthesis and biological evaluation of potent and selective PKD inhibitors
      are described herein. The compounds described in the present study selectively
      inhibit PKD among other putative HDAC kinases. The PKD inhibitors of the present
      study blunt phosphorylation and subsequent nuclear export of HDAC4/5 in response
      to diverse agonists. These compounds further establish the central role of PKD as
      an HDAC4/5 kinase and enhance the current understanding of cardiac myocyte signal
      transduction. The in vivo efficacy of a representative example compound on heart
      morphology is reported herein.

PMID- 20684593
TI  - Structural optimization and biological evaluation of substituted bisphenol A
      derivatives as beta-amyloid peptide aggregation inhibitors.
AB  - The aggregation of Abeta is a crucial step in the etiology of Alzheimer's
      disease. Our previous work showed that Abeta undergoes alpha-helix/beta-sheet
      intermediate structures during the conformational transition, and an Abeta
      aggregation inhibitor (1) was discovered by targeting the intermediates. Here,
      structure optimization toward compound 1 was performed and 34 novel derivatives
      were designed and synthesized. Nine compounds showed more effective inhibitory
      activity than the hit compound 1 in ThT fluorescence assay. Among them, compound
      43 demonstrated more excellent inhibitory potency, which not only can suppress
      the aggregation of Abeta but also can dissolve the preformed fibrils as shown by
      CD spectroscopy, PICUP and AFM assays. Cellular assay indicated that 43 has no
      toxicity to neuronal cells, moreover, can effectively inhibit Abeta(1-42)-induced
      neutrotoxicity and increase the cell viability. Together, on the basis of these
      positive results, these novel chemical structures may provide a promising
      potential for therapeutic applications in AD and other types of neurodegenerative
      disorders.

PMID- 20684594
TI  - Phenylsulfonylfuroxans as modulators of multidrug-resistance-associated protein-1
      and P-glycoprotein.
AB  - A series of furoxan derivatives were studied for their ability to interact with P
      gp and MRP1 transporters in MDCK cells overexpressing these proteins. 3
      Phenylsulfonyl substituted furoxans emerged as the most interesting compounds.
      All of them were capable of inhibiting P-gp, and a few also were capable of
      inhibiting MRP1. Substituents at the 4-position of 3-phenylsulfonylfuroxan
      scaffold were able to modulate the selectivity and the intensity of inhibition.
      In some cases, they reverted MRP1 inhibitor activity, namely, they were capable
      of potentiating MRP1 dependent efflux. When compounds 16 and 17 were
      coadministered with doxorubicin, they restored a high degree of the activity of
      the antibiotic. Preliminary immunoblotting studies carried out on these two
      compounds indicate that they are capable of nitrating P-gp, which in this form is
      likely unable to efflux the antibiotic.

PMID- 20684595
TI  - Quinazolin-4-one derivatives: A novel class of noncompetitive NR2C/D subunit
      selective N-methyl-D-aspartate receptor antagonists.
AB  - We describe a new class of subunit-selective antagonists of N-methyl D-aspartate
      (NMDA)-selective ionotropic glutamate receptors that contain the (E)-3-phenyl-2
      styrylquinazolin-4(3H)-one backbone. The inhibition of recombinant NMDA receptor
      function induced by these quinazolin-4-one derivatives is noncompetitive and
      voltage-independent, suggesting that this family of compounds does not exert
      action on the agonist binding site of the receptor or block the channel pore. The
      compounds described here resemble CP-465,022 ((S)-3-(2-chlorophenyl)-2-[2-(6
      diethylaminomethyl-pyridin-2-yl)-vinyl]-6-fluoro-3H-quinazolin-4-one), a
      noncompetitive antagonist of AMPA-selective glutamate receptors. However,
      modification of ring substituents resulted in analogues with greater than 100
      fold selectivity for recombinant NMDA receptors over AMPA and kainate receptors.
      Furthermore, within this series of compounds, analogues were identified with 50
      fold selectivity for recombinant NR2C/D-containing receptors over NR2A/B
      containing receptors. These compounds represent a new class of noncompetitive
      subunit-selective NMDA receptor antagonists.

PMID- 20684596
TI  - A novel water-soluble gossypol derivative increases chemotherapeutic sensitivity
      and promotes growth inhibition in colon cancer.
AB  - Compound 1 ((-)-gossypol) has been long known as a chemical anticancer agent.
      With its low water solubility and toxicity, it is not widely used as a commercial
      drug. To overcome these disadvantages, several novel derivatives of gossypol were
      designed, synthesized, and analyzed. One of the derivatives, compound 7 (6
      aminopenicillanic acid sodium-gossypolone), was identified with great water
      solubility and anticancer property, suggested by inducing a dramatically decrease
      in Bcl-2 and Bcl-xL protein expression level found in vitro and growth inhibition
      of murine colon tumor in vivo. Furthermore, it was also recognized with less
      toxicity than compound 1 in vivo and significantly increased chemotherapeutic
      sensitivity against colon cancer in combination with traditional chemotherapeutic
      agent 5-fluorouracil. Therefore, it is concluded that compound 7 is superior to
      parent compound 1, and further preclinical studies of compound 7 is necessary for
      colon cancer therapy.

PMID- 20684597
TI  - Identification of the first low-molecular-weight inhibitors of matriptase-2.
AB  - As recently discovered, matriptase-2, a type II transmembrane serine protease,
      plays a crucial role in body iron homeostasis by down-regulating hepcidin
      expression, which results in increased iron levels. Thus, matriptase-2 represents
      a novel target for the development of enzyme inhibitors potentially useful for
      the treatment of systemic iron overload (hemochromatosis). A comparative three
      dimensional model of the catalytic domain of matriptase-2 was generated and
      utilized for structure-based virtual screening in combination with similarity
      searching and knowledge-based compound design. Two N-protected dipeptide amides
      containing a 4-amidinobenzylamide as P1 residue (compounds 1 and 3) were
      identified as the first small molecule inhibitors of matriptase-2 with K(i)
      values of 170 and 460 nM, respectively. An inhibitor of the closely related
      protease matriptase (compound 2, K(i) = 220 nM), with more than 50-fold
      selectivity over matriptase-2, was also identified.

PMID- 20684598
TI  - Development and characterization of new inhibitors of the human and mouse
      hematopoietic prostaglandin D(2) synthases.
AB  - The hematopoietic prostaglandin D(2) synthase has a proinflammatory effect in a
      range of diseases, including allergic asthma, where its product prostaglandin
      D(2) (PGD(2)) has a role in regulating many of the hallmark disease
      characteristics. Here we describe the development and characterization of a novel
      series of hematopoietic prostaglandin D(2) synthase inhibitors with potency
      similar to that of known inhibitors. Compounds N-benzhydryl-5-(3
      hydroxyphenyl)thiophene-2-carboxamide (compound 8) and N-(1-amino-1-oxo-3
      phenylpropan-2-yl)-6-(thiophen-2-yl)nicotinamide (compound 34) demonstrated low
      micromolar potency in the inhibition of the purified enzyme, while only 34
      reduced Toll-like receptor (TLR) inducible PGD(2) production in both mouse
      primary bone marrow-derived macrophages and the human megakaryocytic cell line
      MEG-01S. Importantly, 34 demonstrated a greater selectivity for inhibition of
      PGD(2) synthesis versus other eicosanoids that lie downstream of PGH(2) (PGE(2)
      and markers of prostacyclin (6-keto PGF(1alpha)) and thromboxane (TXB(2))) when
      compared to the known inhibitors HQL-79 (compound 1) and 2-phenyl-5-(1H-pyrazol-3
      yl)thiazole (compound 2). Compound 34 therefore represents a selective
      hematopoietic prostaglandin D(2) synthase inhibitor.

PMID- 20684599
TI  - Substituted E-3-(3-indolylmethylene)-1,3-dihydroindol-2-ones with antitumor
      activity. In depth study of the effect on growth of breast cancer cells.
AB  - The synthesis of new substituted E-3-(3-indolylmethylene)-1,3-dihydroindol-2-ones
      is reported. The antitumor activity was evaluated according to protocols
      available at the National Cancer Institute (NCI), Bethesda, MD. Structure
      activity relationships are discussed. The action of selected compounds was
      investigated in MCF-7 breast cancer cells. The ability of these derivatives to
      inhibit cellular proliferation was accompanied by increased level of p53 and its
      transcriptional targets p21 and Bax, interference in the cell cycle progression
      with cell accumulation in the G2/M phase, and activation of apoptosis.

PMID- 20684601
TI  - Computer-aided optimization of phosphinic inhibitors of bacterial ureases.
AB  - Urease inhibitors can be considered as a tool to control the damaging effect of
      ureolytic bacteria infections in humans which occur commonly in the developed
      countries. Computer-aided optimization of the aminomethylphosphinate structures
      by modifying both their N- and P-termini led to the invention of a novel group of
      inhibitors of bacterial ureases. Introduction of P-hydroxymethyl group into the
      molecule resulted in considerable increase of the inhibitory activity against
      enzymes purified from Bacillus pasteurii and Proteus vulgaris as compared with
      their P-methyl counterparts described previously. The designed compounds
      represent a competitive reversible class of urease inhibitors. The most potent, N
      methyl-aminomethyl-P-hydroxymethylphosphinic acid, displayed K(i) = 360 nM
      against P. vulgaris enzyme.

PMID- 20684600
TI  - Biological diversity from a structurally diverse library: systematically scanning
      conformational space using a pyranose scaffold.
AB  - Success in discovering bioactive peptide mimetics is often limited by the
      difficulties in correctly transposing known binding elements of the active
      peptide onto a small and metabolically more stable scaffold while maintaining
      bioactivity. Here we describe a scanning approach using a library of pyranose
      based peptidomimetics that is structurally diverse in a systematic manner,
      designed to cover all possible conformations of tripeptide motifs containing two
      aromatic groups and one positive charge. Structural diversity was achieved by
      efficient selection of various chemoforms, characterized by a choice of pyranose
      scaffold of defined chirality and substitution pattern. A systematic scanning
      library of 490 compounds was thus designed, produced, and screened in vitro for
      activity at the somatostatin (sst(1-5)) and melanin-concentrating hormone
      (MCH(1)) receptors. Bioactive compounds were found for each target, with specific
      chemoform preferences identified in each case, which can be used to guide follow
      on drug discovery projects without the need for scaffold hopping.

PMID- 20684602
TI  - An efficient approach to the discovery of potent inhibitors against
      glycosyltransferases.
AB  - We describe a standardized approach for searching potent and selective inhibitors
      of glycosyltransferases by high throughput quantitative MALDI-TOFMS-based
      screening of focused compound libraries constructed by 1,3-dipolar cycloaddition
      of the desired azidosugar nucleotides with various alkynes. An aminooxy
      functionalized reagent with a stable isotope was conjugated with oligosaccharides
      to afford glycopeptides as acceptor substrates with improved ion sensitivity.
      Enhanced ionization potency of new substrates allowed for MALDI-TOFMS-based
      facile and quantitative analysis of enzymatic glycosylation in the presence of
      glycosyl donor substrates. A non-natural synthetic sugar nucleotide was
      identified to be the first highly specific inhibitor for rat recombinant alpha2,3
      (N)-sialyltransferase (alpha2,3ST, IC(50) = 8.2 microM), while this compound was
      proved to become a favorable substrate for rat recombinant alpha2,6-(N)
      sialyltransferase (alpha2,6ST, K(m) = 125 microM). Versatility of this strategy
      was demonstrated by identification of two selective inhibitors for human
      recombinant alpha1,3-fucosyltransferase V (alpha1,3-FucT, K(i) = 293 nM) and
      alpha1,6-fucosyltransferase VIII (alpha1,6-FucT, K(i) = 13.8 microM).

PMID- 20684603
TI  - Discovery of 6-(aminomethyl)-5-(2,4-dichlorophenyl)-7-methylimidazo[1,2
      a]pyrimidine-2-carboxamides as potent, selective dipeptidyl peptidase-4 (DPP4)
      inhibitors.
AB  - Continued structure-activity relationship (SAR) exploration within our previously
      disclosed azolopyrimidine containing dipeptidyl peptidase-4 (DPP4) inhibitors led
      us to focus on an imidazolopyrimidine series in particular. Further study
      revealed that by replacing the aryl substitution on the imidazole ring with a
      more polar carboxylic ester or amide, these compounds displayed not only
      increased DPP4 binding activity but also significantly reduced human ether-a-go
      go related gene (hERG) and sodium channel inhibitory activities. Additional
      incremental adjustment of polarity led to permeable molecules which exhibited
      favorable pharmacokinetic (PK) profiles in preclinical animal species. The active
      site binding mode of these compounds was determined by X-ray crystallography as
      exemplified by amide 24c. A subsequent lead molecule from this series, (+)-6
      (aminomethyl)-5-(2,4-dichlorophenyl)-N-(1-ethyl-1H-pyrazol-5-yl)-7
      methylimidazo[1,2-a]pyrimidine-2-carboxamide (24s), emerged as a potent,
      selective DPP4 inhibitor that displayed excellent PK profiles and in vivo
      efficacy in ob/ob mice.

PMID- 20684604
TI  - Design, synthesis, enzyme-inhibitory activity, and effect on human cancer cells
      of a novel series of jumonji domain-containing protein 2 histone demethylase
      inhibitors.
AB  - Selective inhibitors of Jumonji domain-containing protein (JMJD) histone
      demethylases are candidate anticancer agents as well as potential tools for
      elucidating the biological functions of JMJDs. On the basis of the crystal
      structure of JMJD2A and a homology model of JMJD2C, we designed and prepared a
      series of hydroxamate analogues bearing a tertiary amine. Enzyme assays using
      JMJD2C, JMJD2A, and prolyl hydroxylases revealed that hydroxamate analogue 8 is a
      potent and selective JMJD2 inhibitor, showing 500-fold greater JMJD2C-inhibitory
      activity and more than 9100-fold greater JMJD2C-selectivity compared with the
      lead compound N-oxalylglycine 2. Compounds 17 and 18, prodrugs of compound 8,
      each showed synergistic growth inhibition of cancer cells in combination with an
      inhibitor of lysine-specific demethylase 1 (LSD1). These findings suggest that
      combination treatment with JMJD2 inhibitors and LSD1 inhibitors may represent a
      novel strategy for anticancer chemotherapy.

PMID- 20684605
TI  - Crystal structure-based selective targeting of the pyridoxal 5'-phosphate
      dependent enzyme kynurenine aminotransferase II for cognitive enhancement.
AB  - Fluctuations in the brain levels of the neuromodulator kynurenic acid may control
      cognitive processes and play a causative role in several catastrophic brain
      diseases. Elimination of the pyridoxal 5'-phosphate dependent enzyme kynurenine
      aminotransferase II reduces cerebral kynurenic acid synthesis and has
      procognitive effects. The present description of the crystal structure of human
      kynurenine aminotransferase II in complex with its potent and specific primary
      amine-bearing fluoroquinolone inhibitor (S)-(-)-9-(4-aminopiperazin-1-yl)-8
      fluoro-3-methyl-6-oxo-2,3-dihydro-6H-1-oxa-3a-azaphenalene-5-carboxylic acid (BFF
      122) should facilitate the structure-based development of cognition-enhancing
      drugs. From a medicinal chemistry perspective our results demonstrate that the
      issue of inhibitor specificity for highly conserved PLP-dependent enzymes could
      be successfully addressed.

PMID- 20684606
TI  - Synthesis and in vivo evaluation of phenethylpiperazine amides: selective 5
      hydroxytryptamine(2A) receptor antagonists for the treatment of insomnia.
AB  - Recent developments in sleep research suggest that antagonism of the serotonin 5
      HT(2A) receptor may improve sleep maintenance insomnia. We herein report the
      discovery of a series of potent and selective serotonin 5-HT(2A) receptor
      antagonists based on a phenethylpiperazine amide core structure. When tested in a
      rat sleep pharmacology model, these compounds increased both sleep consolidation
      and deep sleep. Within this series of compounds, an improvement in the metabolic
      stability of early leads was achieved by introducing a carbonyl group into the
      phenethylpiperazine linker. Of note, compounds 14 and 27 exhibited potent 5
      HT(2A) receptor binding affinity, high selectivity over the 5-HT(2C) receptor,
      favorable CNS partitioning, and good pharmacokinetic and early safety profiles.
      In vivo, these two compounds showed dose-dependent, statistically significant
      improvements on deep sleep (delta power) and sleep consolidation at doses as low
      as 0.1 mg/kg.

PMID- 20684607
TI  - Scaffold hopping using two-dimensional fingerprints: true potential, black magic,
      or a hopeless endeavor? Guidelines for virtual screening.
AB  - The scaffold hopping potential of popular 2D fingerprints has been thoroughly
      investigated. We have found that these types of fingerprints have at least
      limited scaffold hopping ability including early enrichment of small numbers of
      active scaffolds at high database ranks. However, it has not been possible to
      derive Tanimoto coefficient value ranges for individual fingerprints that are
      generally preferred for scaffold hopping. For selected fingerprints, similarity
      threshold values have been identified that yield small database selection sets
      having a high probability to contain a few active scaffolds. Furthermore,
      essentially all tested fingerprints have shown the ability to enrich scaffold
      hops in approximately 1% of a screening database. For the test cases reported
      herein, selecting 0.5-1% of the screening database yields approximately 25% of
      the available scaffolds. On the basis of our findings, practical guidelines for
      virtual screening using different types of 2D fingerprints have been formulated.

PMID- 20684608
TI  - Tetrahydroisoquinoline derivatives as highly selective and potent Rho kinase
      inhibitors.
AB  - Rho kinase (ROCK) is a promising drug target for the treatment of many diseases
      including hypertension, multiple sclerosis, cancer, and glaucoma. The structure
      activity relationships (SAR) around a series of tetrahydroisoquinolines were
      evaluated utilizing biochemical and cell-based assays to measure ROCK inhibition.
      These novel ROCK inhibitors possess high potency, high selectivity, and
      appropriate pharmacokinetic properties for glaucoma applications. The lead
      compound, 35, had subnanomolar potency in enzyme ROCK-II assays as well as
      excellent cell-based potency (IC(50) = 51 nM). In a kinase panel profiling, 35
      had an off-target hit rate of only 1.6% against 442 kinases. Pharmacology studies
      showed that compound 35 was efficacious in reducing intraocular pressure (IOP) in
      rats with reasonably long duration of action. These results suggest that compound
      35 may serve as a promising agent for further development in the treatment of
      glaucoma.

PMID- 20684609
TI  - Synthesis and biological characterization of novel charge-deficient spermine
      analogues.
AB  - Biogenic polyamines, spermidine and spermine, are positively charged at
      physiological pH. They are present in all cells and essential for their growth
      and viability. Here we synthesized three novel derivatives of the isosteric
      charge-deficient spermine analogue 1,12-diamino-3,6,9-triazadodecane (SpmTrien,
      5a) that are N(1)-Ac-SpmTrien (5c), N(12)-Ac-SpmTrien (5b), and N(1),N(12)
      diethyl-1,12-diamino-3,6,9-triazadodecane (N(1),N(12)-Et(2)-SpmTrien, 5d). 5a and
      5d readily accumulated in DU145 cells at the same concentration range as natural
      polyamines and moderately competed for the uptake with putrescine (1) but not
      with spermine (4a) or spermidine (2). 5a efficiently down-regulated ornithine
      decarboxylase and decreased polyamine levels, while 5d proved to be inefficient,
      compared with N(1),N(11)-diethylnorspermine (6). None of the tested analogues
      were substrates for human recombinant spermine oxidase, but those having free
      aminoterminus, including 1,8-diamino-3,6-diazaoctane (Trien, 3a), were acetylated
      by mouse recombinant spermidine/spermine N(1)-acetyltransferase. 5a was
      acetylated to 5c and 5b, and the latter was further metabolized by
      acetylpolyamine oxidase to 3a, a drug used to treat Wilson's disease. Thus, 5a is
      a bioactive precursor of 3a with enhanced bioavailability.

PMID- 20684610
TI  - Replacement of imidazolyl by pyridyl in biphenylmethylenes results in selective
      CYP17 and dual CYP17/CYP11B1 inhibitors for the treatment of prostate cancer.
AB  - Androgens are well-known to stimulate prostate cancer (PC) growth. Thus, blockade
      of androgen production in testes and adrenals by CYP17 inhibition is a promising
      strategy for the treatment of PC. Moreover, many PC patients suffer from
      glucocorticoid overproduction, and importantly mutated androgen receptors can be
      stimulated by glucocorticoids. In this study, the first dual inhibitor of CYP17
      and CYP11B1 (the enzyme responsible for the last step in glucocorticoid
      biosynthesis) is described. A series of biphenylmethylene pyridines has been
      designed, synthesized, and tested as CYP17 and CYP11B1 inhibitors. The most
      active compounds were also tested for selectivity against CYP11B2 (aldosterone
      synthase), CYP19 (aromatase), and hepatic CYP3A4. In detail, compound 6 was
      identified as a dual inhibitor of CYP17/CYP11B1 (IC(50) values of 226 and 287 nM)
      showing little inhibition of the other enzymes as well as compound 9 as a
      selective, highly potent CYP17 inhibitor (IC(50) = 52 nM) exceeding abiraterone
      in terms of activity and selectivity.

PMID- 20684611
TI  - Design of potent inhibitors of human RAD51 recombinase based on BRC motifs of
      BRCA2 protein: modeling and experimental validation of a chimera peptide.
AB  - We have previously shown that a 28-amino acid peptide derived from the BRC4 motif
      of BRCA2 tumor suppressor inhibits selectively human RAD51 recombinase (HsRad51).
      With the aim of designing better inhibitors for cancer treatment, we combined an
      in silico docking approach with in vitro biochemical testing to construct a
      highly efficient chimera peptide from eight existing human BRC motifs. We built a
      molecular model of all BRC motifs complexed with HsRad51 based on the crystal
      structure of the BRC4 motif-HsRad51 complex, computed the interaction energy of
      each residue in each BRC motif, and selected the best amino acid residue at each
      binding position. This analysis enabled us to propose four amino acid
      substitutions in the BRC4 motif. Three of these increased the inhibitory effect
      in vitro, and this effect was found to be additive. We thus obtained a peptide
      that is about 10 times more efficient in inhibiting HsRad51-ssDNA complex
      formation than the original peptide.

PMID- 20684612
TI  - The sugar ring of the nucleoside is required for productive substrate positioning
      in the active site of human deoxycytidine kinase (dCK): implications for the
      development of dCK-activated acyclic guanine analogues.
AB  - The low toxicity of acyclovir (ACV) is mainly due to the fact that human
      nucleoside kinases have undetectable phosphorylation rates with this acyclic
      guanine analogue. In contrast, herpes virus thymidine kinase (HSV1-TK) readily
      activates ACV. We wanted to understand why human deoxycytidine kinase (dCK),
      which is related to HSV1-TK and phosphorylates deoxyguanosine, does not accept
      acyclic guanine analogues as substrates. Therefore, we crystallized dCK in
      complex with ACV at the nucleoside phosphoryl acceptor site and UDP at the
      phosphoryl donor site. The structure reveals that while ACV does bind at the dCK
      active site, it does so adopting a nonproductive conformation. Despite binding
      ACV, the enzyme remains in the open, inactive state. In comparison to ACV binding
      to HSV1-TK, in dCK, the nucleoside base adopts a different orientation related by
      about a 60 degrees rotation. Our analysis suggests that dCK would phosphorylate
      acyclic guanine analogues if they can induce a similar rotation.

PMID- 20684613
TI  - Understanding and predicting druggability. A high-throughput method for detection
      of drug binding sites.
AB  - Druggability predictions are important to avoid intractable targets and to focus
      drug discovery efforts on sites offering better prospects. However, few
      druggability prediction tools have been released and none has been extensively
      tested. Here, a set of druggable and nondruggable cavities has been compiled in a
      collaborative platform ( http://fpocket.sourceforge.net/dcd ) that can be used,
      contributed, and curated by the community. Druggable binding sites are often
      oversimplified as closed, hydrophobic cavities, but data set analysis reveals
      that polar groups in druggable binding sites have properties that enable them to
      play a decisive role in ligand recognition. Finally, the data set has been used
      in conjunction with the open source fpocket suite to train and validate a
      logistic model. State of the art performance was achieved for predicting
      druggability on known binding sites and on virtual screening experiments where
      druggable pockets are retrieved from a pool of decoys. The algorithm is free,
      extremely fast, and can effectively be used to automatically sieve through
      massive collections of structures ( http://fpocket.sourceforge.net ).

PMID- 20684614
TI  - Synthesis and structure-activity relationships of novel 8a-aza-8a
      homoerythromycin A ketolides.
AB  - A series of novel 6-O-substituted 8a-aza-8a-homoerythromycin A ketolides was
      synthesized and evaluated for in vitro antibacterial activity. Key strategic
      elements of the synthesis include the base-induced E-Z isomerization of 3-O
      descladinosyl-6-O-allylerythromycin A 9(E)-oxime followed by ring-expanding
      reaction of the resulting 9(Z)-oxime via Beckmann rearrangement. The ketolides
      showed potent activity against a variety of erythromycin-susceptible and
      macrolide-lincosamide-streptogramin B (MLS(B)) resistant Gram-positive and
      fastidious Gram-negative pathogens. The best compounds in this series overcome
      all types of resistance in relevant clinical Gram-positive pathogens and display
      in vitro activity comparable to telithromycin and cethromycin.

PMID- 20684615
TI  - Synthesis and resolution of cis-(+/-)-methyl (1R,2S/1S,2R)-2-[(4-hydroxy-4
      phenylpiperidin-1-yl)methyl]-1-(4-methylphenyl)cyclopropanecarboxylate [(+/-)
      PPCC)]: new sigma receptor ligands with neuroprotective effect.
AB  - The enantiomers of cis-(+/-)-methyl (1R,2S/1S,2R)-2-[(4-hydroxy-4-phenylpiperidin
      1-yl)methyl]-1-(4-methylphenyl)cyclopropanecarboxylate [1, (+/-)-PPCC], a
      selective sigma ligand, were synthesized. The (+)- and (-)-enantiomers bind
      predominantly to sigma(1) receptors and have a reduced sigma(2) affinity. Both
      individually restore the astroglial oxidative status modified by glutamate,
      counteracting also transglutaminase-2 overexpression. They exhibited in vivo anti
      opioid effects on kappa opioid (KOP) receptor-mediated analgesia. Our findings
      demonstrate that the enantiomers display mainly sigma(1) agonist activity and
      that they have neuroprotective effects.

PMID- 20684616
TI  - Glucosylated deferiprone and its brain uptake: implications for developing
      glucosylated hydroxypyridinone analogues intended to cross the blood-brain
      barrier.
AB  - This report presents that Deferiprone, the only clinically used 3-hydroxypyridin
      4-one (HPO), is able to penetrate the blood-brain barrier (BBB) in guinea pigs,
      whereas its glucosylated analogue is unable to do so. This finding is contrary to
      published information suggesting that the glucosylation of HPOs is a viable means
      of enhancing the brain uptake of this group of compounds.

PMID- 20684617
TI  - A solution study of silica condensation and speciation with relevance to in vitro
      investigations of biosilicification.
AB  - Requiring mild synthesis conditions and possessing a high level of organization
      and functionality, biosilicas constitute a source of wonder and inspiration for
      both materials scientists and biologists. In order to understand how such
      biomaterials are formed and to apply this knowledge to the generation of novel
      bioinspired materials, a detailed study of the materials, as formed under
      biologically relevant conditions, is required. In this contribution, data from a
      detailed study of silica speciation and condensation using a model bioinspired
      silica precursor (silicon catechol complex, SCC) is presented. The silicon
      complex quickly and controllably dissociates under neutral pH conditions to well
      defined, metastable solutions of orthosilicic acid. The formation of
      silicomolybdous (blue) complexes was used to monitor and study different stages
      of silicic acid condensation. In parallel, the rates of silicomolybdic (yellow)
      complex formation, with mathematical modeling of the species present, was used to
      follow the solution speciation of polysilicic acids. The results obtained from
      the two assays correlate well. Monomeric silicic acid, trimeric silicic acids,
      and different classes of oligomeric polysilicic acids and silica nuclei can be
      identified and their periods of stability during the early stages of silica
      condensation measured. For experiments performed at a range of temperatures (273
      323 K), an activation energy of 77 kJ.mol(-1) was obtained for the formation of
      trimers. The activation energies for the forward and reverse condensation
      reactions for addition of monomers to polysilicic acids (273-293 +/- 1 K) were
      55.0 and 58.6 kJ.mol(-1), respectively. For temperatures above 293 K, these
      energies were reduced to 6.1 and 7.3 kJ.mol(-1), indicating a probable change in
      the prevailing condensation mechanism. The impact of pH on the rates of
      condensation were measured. There was a direct correlation between the apparent
      third-order rate constant for trimer formation and pH (4.7-6.9 +/- 0.1) while
      values for the reversible first-order rates reached a plateau at circumneutral
      pH. These different behaviors are discussed with reference to the generally
      accepted mechanism for silica condensation in which anionic silicate solution
      species are central to the condensation process. The results presented in this
      paper support the use of precursors such as silicon catecholate complexes in the
      study of biosilicification in vitro. Further detailed experimentation is needed
      to increase our understanding of specific biomolecule silica interactions that
      ultimately generate the complex, finely detailed siliceous structures we observe
      in the world around us.

PMID- 20684618
TI  - Phase separation in symmetric mixtures of oppositely charged rodlike
      polyelectrolytes.
AB  - Phase separation in salt-free symmetric mixtures of oppositely charged rodlike
      polyelectrolytes is studied using quasi-analytical calculations. Stability
      analyses for the isotropic-isotropic and the isotropic-nematic phase transitions
      in the mixtures are carried out and demonstrate that electrostatic interactions
      favor nematic ordering. Coexistence curves for the symmetric mixtures are also
      constructed and are used to examine the effects of linear charge density and
      electrostatic interaction strength on rodlike polyelectrolyte complexation. It is
      found that the counterions are uniformly distributed in the coexisting phases for
      low electrostatic interaction strengths dictated by the linear charge density of
      the polyelectrolytes and Bjerrum's length. However, the counterions also
      partition along with the rodlike polyelectrolytes with an increase in the
      electrostatic interaction strength. It is shown that the number density of the
      counterions is higher in the concentrated (or "coacervate") phase than in the
      dilute (or supernatant) phase. In contrast to such rodlike mixtures, flexible
      polyelectrolyte mixtures can undergo only isotropic-isotropic phase separation. A
      comparison of the coexistence curves for weakly charged rodlike mixtures with
      those of analogous flexible polyelectrolyte mixtures reveals that the
      electrostatic driving force for the isotropic-isotropic phase separation is
      stronger in the flexible mixtures.

PMID- 20684619
TI  - Fluorescence anisotropy of hydrophobic probes in poly(N-decylacrylamide)-block
      poly(N,N-diethylacrylamide) block copolymer aqueous solutions: evidence of
      premicellar aggregates.
AB  - Fluorescent probes, coumarin 153 (C153) and octadecylrhodamine B (ORB), were used
      to study the self-assembly in water of poly(N-decylacrylamide)-block-poly(N,N
      diethylacrylamide), (PDcA(11)-block-PDEA(295); M(n) = 40 300 g mol(-1); M(w)/M(n)
      = 1.01). From the variation of both the fluorescence intensity and the
      solvatochromic shifts of C153 with polymer concentration, the critical micelle
      concentration (CMC) was determined as 1.8 +/- 0.1 microM. On the other hand,
      steady-state anisotropy measurements showed the presence of premicellar
      aggregates below the CMC. Time-resolved fluorescence anisotropy evidenced that
      ORB is located in the premicellar aggregates and the micelle core, while C153 is
      partitioned between the aggregates and the water phase. The micelle core contains
      both semicrystalline and amorphous regions. In the semicrystalline regions the
      probes cannot rotate, while in the amorphous regions the rotational correlation
      times correlate well with the hydrodynamic volume of the probes. The amorphous
      region of the micelle core is relatively fluid, reflecting the large free-volume
      accessible to the probes.

PMID- 20684620
TI  - Specific anion effects on the growth of a polyelectrolyte multilayer in single
      and mixed electrolyte solutions investigated with quartz crystal microbalance.
AB  - The specific anion effects on the deposition of a multilayer formed by
      poly(sodium 4-styrene sulfonate) (PSS) and poly(diallyldimethylammonium chloride)
      (PDDA) have been investigated by use of quartz crystal microbalance with
      dissipation (QCM-D) in single and mixed electrolyte solutions. In the case of
      single electrolyte solutions, the frequency change (-Deltaf) demonstrates that
      the multilayer in NaBr, NaClO(3), and NaCl solutions grows in a nonlinear mode,
      which is dominated by the penetration of PSS. In NaF, CH(3)COONa, NaH(2)PO(4),
      and Na(2)SO(4) solutions, the multilayer growth mainly determined by the
      conformation of PDDA chains exhibits a linear mode. The growth shows a mode in
      between in NaHCO(3) solution. The dissipation change (DeltaD) has slight
      dependence on anion species except in the cases of Br(-), HCO(3)(-), and SO(4)(2
      ). DeltaD remarkably increases with layer number in NaHCO(3) solution, indicating
      the formation of a relatively loose multilayer. In a mixed electrolyte solution
      containing chaotropic and kosmotropic anions, the multilayer growth is dominated
      by the chaotropic anions due to the anion competition effects. The effects of
      anions on the deposition of multilayer are nonadditive.

PMID- 20684621
TI  - Polypropylene injection molded part with novel macroscopic bamboo-like bionic
      structure.
AB  - A macroscopic bamboo-like bionic structure was fabricated in the injection-molded
      bar of isotactic polypropylene via the combined effect of "melt manipulation" and
      beta-nucleator. Such structure consists of strengthened shell zone with high
      orientation and low beta-phase amount, and toughened core part with isotropic
      texture and dominant beta-modification. The influences of shear intensity on
      structural hierarchies, polymorphism, and crystalline morphology were estimated.
      Both toughness and strength can be significantly improved with increasing shear
      intensity on the bamboo-like structure. Our study suggested an alternative
      approach to achieve excellent comprehensive mechanics in polypropylene via
      macroscopic structural design during the practical molding process.

PMID- 20684622
TI  - Dynamics in the process of formation of anisotropic chitosan hydrogel.
AB  - To control the dynamics of dialysis-induced anisotropic gel formation, we have
      derived a theoretical expression for the development of the gel layer for a
      simple case where no cross-link sites for cross-linking agents exists and the
      inflow and the outflow of low molecular weight components through the dialysis
      membrane modify the state of polymer molecules to meet the gelation condition. A
      series of experiments using chitosan solution were done as a model case. The
      experimental results were compared with asymptotic expressions of the time
      development equation predicted by theory, and the compatibility of the
      theoretical picture was examined.

PMID- 20684623
TI  - Flow cytometry as a novel tool to evaluate and separate vesicles using
      characteristic scatter signatures.
AB  - Vesicles are usually characterized for their structure by microscopy or, less
      often, by the addition of fluorescent dyes in a flow cytometer. We present a new
      method of studying these structures and associated forms by forward and side
      scatter analysis on a flow cytometer which has the advantage of simultaneous
      handling of large population of vesicles to identify their shapes and
      lamellarities. The technique is suitable for several types of vesicular
      structures like Multivesicular vesicles (MVV), multilamellar and unilamellar
      vesicles. Characteristic signatures are given by tubular structures and fine
      features thereon allow detection of complex structures such as fused and
      ellipsoidal forms. Coexistence of tubular and spherical structures, such as those
      known to form when surfactants/salt solutions are diluted, can clearly be
      detected by the signature pattern, which separates into two distinctly
      identifiable populations. The population can be sorted or separated easily based
      on these signatures and such sorting has allowed us to confirm our findings by
      microscopic observations. This novel method can thus be used for concurrent
      observations of vesicle populations with dye or more advantageously without
      employing any fluorescent tag.

PMID- 20684624
TI  - Nitric oxide adsorption effects on metal phthalocyanines.
AB  - The adsorption of nitric oxide (NO) on various metal phthalocyanines (MPc, M =
      Mn, Fe, Co) has been studied using first-principles calculations based on density
      functional theory (DFT). In this study, we investigated the fully optimized
      geometries and electronic structure of MPc. We found that the electronic
      structures of metal atoms are essential in shaping the ground-state electronic
      structure near the Fermi level. These states are defined mostly by the d orbitals
      of the transition-metal atoms and, to some degree, by the states of nitrogen and
      carbon atoms of the inner rings. The numerical calculations showed that NO
      strongly chemisorbs to the metal atom with an end-on configuration and results in
      a change in geometric and electronic structures of MPc. The N-O bond lengths are
      slightly longer than that of the isolated NO molecule. The orbital energy levels
      are shifted with respect to the Fermi level. The HOMO-LUMO gap widens as compared
      to bare MPc. These changes are attributed to the hybridization of the pi* orbital
      of NO and the d orbitals of the transition metal. Specifically, the interaction
      between dpi and the pi* orbital is significant for MnPc-NO, while the
      hybridization of d(z(2)) and the pi* orbital plays an important role in CoPc-NO.

PMID- 20684625
TI  - Diversity observed in the nanostructure of protic ionic liquids.
AB  - The nanostructure of a series of 20 protic ionic liquids (PILs) has been
      investigated using small- and wide-angle X-ray scattering (SAXS and WAXS). The
      PILs contained alkylammonium, dialkylammonium, trialkylammonium, and cyclic
      ammonium cations combined with organic or inorganic anions. The presence of
      hydroxyl and methoxy substituents on the alkyl chains of the cations was also
      explored. Many of the PILs showed a nanostructure resulting from segregation of
      the polar and nonpolar components of the ionic liquid. It was found that this
      segregation was enhanced for longer alkyl chains, with a corresponding increase
      in the length scale, whereas the presence of hydroxyl groups on the alkyl chains
      led to much less ordered liquids. The broad range of protic ionic liquids studied
      allowed several structure-property relationships to be established. The
      solvophobic effect was shown to be dependent on the nanostructure of the PILs.
      These PILs support amphiphile self-assembly, and it was shown that the less
      structured PILs had more "water-like" behavior in the diversity of lyotropic
      liquid-crystal phases supported, and the thermal stability ranges for these
      phases.

PMID- 20684626
TI  - NMR characterization of the aggregation state of the azo dye sunset yellow in the
      isotropic phase.
AB  - The azo dye sunset yellow is known to form lyotropic liquid crystals as a
      function of both temperature and sample composition. Numerous studies have been
      performed to investigate the aggregation processes in these liquid crystals;
      however, less attention has been paid to the nature of the aggregates in the
      isotropic phase. In this study we employ diffusion nuclear magnetic resonance
      methods to investigate the hydrodynamic properties of sunset yellow aggregates at
      a range of concentrations in isotropic solution. The results of these experiments
      are interpreted in terms of a simple thermodynamic model for aggregation and
      suggest that the aggregates are comprised of tens to hundreds of monomer units at
      the concentrations investigated. The results also demonstrate that the average
      number of molecules per aggregate is a factor of approximately 5 larger than
      previously reported.

PMID- 20684627
TI  - RNA structure determination using SAXS data.
AB  - Exploiting the experimental information from small-angle X-ray solution
      scattering (SAXS) in conjunction with structure prediction algorithms can be
      advantageous in the case of ribonucleic acids (RNA), where global restraints on
      the 3D fold are often lacking. Traditional usage of SAXS data often starts by
      attempting to reconstruct the molecular shape ab initio, which is subsequently
      used to assess the quality of a model. Here, an alternative strategy is explored
      whereby the models from a very large decoy set are directly sorted according to
      their fit to the SAXS data. For rapid computation of SAXS patterns, the method
      developed here makes use of a coarse-grained representation of RNA. It also
      accounts for the explicit treatment of the contribution to the scattering of
      water molecules and ions surrounding the RNA. The method, called Fast-SAXS-RNA,
      is first calibrated using a tRNA (tRNA-val) and then tested on the P4-P6 fragment
      of group I intron (P4-P6). Fast-SAXS-RNA is then used as a filter for decoy
      models generated by the MC-Fold and MC-Sym pipeline, a suite of RNA 3D all-atom
      structure algorithms that encode and exploit RNA 3D architectural principles. The
      ability of Fast-SAXS-RNA to discriminate native folds is tested against three
      widely used RNA molecules in molecular modeling benchmarks: the tRNA, the P4-P6,
      and a synthetic hairpin suspected to assemble into a homodimer. For each
      molecule, a large pool of decoys are generated, scored, and ranked using Fast
      SAXS-RNA. The method is able to identify low-rmsd models among top ranking
      structures, for both tRNA and P4-P6. For the hairpin, the approach correctly
      identifies the dimeric state as the solution structure over the monomeric state
      and alternative secondary structures. The method offers a powerful strategy for
      recognizing native RNA conformations as well as multimeric assemblies and
      alternative secondary structures, thus enabling high-throughput RNA structure
      determination using SAXS data.

PMID- 20684628
TI  - Decreased osmotic pressure via interfacial charge clustering.
AB  - Behaviors of a model interfacial system featuring the clustering of discrete,
      mobile wall charges and a counterion solution are investigated. The results
      demonstrate that even very small localized charge clusters produce significant
      effects for the osmotic pressure, effects that are not adequately represented in
      common colloidal models. We observe a pronounced decrease in osmotic pressure
      where a certain level of clustering is attained, with potentially significant
      implications for theories of colloidal stability and biochemical processes at
      microscopic length scales. The stable level of wall charge clustering, and thus
      the osmotic pressure, is found to be variable in the addition of an attractive
      potential, as measured via the excess free energy of clustering.

PMID- 20684629
TI  - Ultrafast electron transfer dynamics in micellar media using surfactant as the
      intrinsic electron acceptor.
AB  - Ultrafast photoinduced intermolecular electron transfer (ET) dynamics involving 7
      aminocoumarin derivatives as electron donor and pyridinium moiety of surfactant
      molecules in cetylpyridinium chloride (CPC) micelle as electron acceptor has been
      investigated to understand the role of separation and orientation of reactants on
      micellar ET reactions. Unlike in noninteracting micelles (like Triton-X-100,
      sodium dodecyl sulfate, dodecyltrimethylammonium bromide, etc.), where surfactant
      separated donor-acceptor pairs are understood to give the ultrafast ET component
      with the shortest time constant in the range of approximately 4 ps, in CPC
      micelles with pyridinium moiety as the intrinsic acceptor the ultrafast ET
      component is found to be in the subpicosecond time scale (of around 240 fs). This
      time scale is very similar to the values reported in the cases of ultrafast ET
      reactions involving coumarin dyes in electron-donating solvents. The ultrafast ET
      times in CPC micelles are significantly faster than the diffusive solvation
      dynamics in the micellar media. Correlation of the observed ET rates in the
      present cases with the free-energy changes of the reactions shows the inverse
      bell-shaped correlation, predicted by Marcus ET theory. Interestingly, the onset
      of the Marcus inversion appears at a relatively lower exergonicity, which is
      attributed to the nonequilibrium solvent configuration during the ultrafast ET
      reaction, as envisaged from two-dimensional ET (2DET) model. Along with the
      ultrafast ET component, there are also slower ET components in these systems,
      which are attributed to those close-contact donor-acceptor populations in the
      micelles that have relatively weaker electronic coupling due to improper
      orientation of the interacting donor-acceptor pairs. The present results suggest
      that, along with the shifting of Marcus inversion at lower exergonicity, the ET
      rates can also be maximized in a micellar media by using surfactant molecule as
      an intrinsic reactant.

PMID- 20684630
TI  - Molecular dynamics study of the influence of calcium ions on foam stability.
AB  - Molecular dynamic simulations have been performed with three common surfactants
      [linear alkylbenzene sulfonate (LAS), sodium dodecyl sulfate (SDS), and
      heptaethylene glycol monododecyl ether (C(12)E(7))] to investigate the influence
      of calcium ions on foam stability. The foam stability was examined by simulating
      film rupture during which critical thickness was measured. The simulation results
      showed that as Ca(2+) concentration increased, SDS showed a significant decrease
      in foam stability, but LAS and C(12)E(7) nearly maintained foam performance and
      remained free from calcium ions. This was validated by our experimental results.
      Microscopic interaction configurations between Ca(2+) and surfactants were
      analyzed through the interaction distance distribution and the binding number
      distribution. We found there are mainly two interaction distances between the
      calcium ion and the oxygen atom of surfactants, the short distance (
      approximately 0.23 nm) and the longer distance ( approximately 0.45 nm). Results
      showed that LAS has many more interaction configurations at the short distance
      and SDS has fewer configurations at the short distance. This indicates that the
      foam stability of the surfactant less influenced by calcium ions relates to
      enhanced interaction configurations at the short distance.

PMID- 20684631
TI  - Thermal and structural study of the crystal phases and mesophases in the lithium
      and thallium(i) propanoates and pentanoates binary systems: formation of mixed
      salts and stabilization of the ionic liquid crystal phase.
AB  - The temperature and enthalpy vs composition phase diagrams of the binary systems
      [xC(2)H(5)CO(2)Li + (1 - x)C(2)H(5)CO(2)Tl], and [x(n-C(4)H(9)CO(2)Li) + (1 - x)n
      C(4)H(9)CO(2)Tl], where x is the mole fraction, were determined by DSC. Both
      binary systems display the formation of one 2:1 mixed salt each (at x = 0.667)
      that appear as a peritectic (incongruent melting) at T(fus) = 512.0 K, and T(fus)
      = 461.1 K, with Delta(fus)H(m) = 13.76 and 8.08 kJ.mol(-1) for Li-Tl (I)
      propanoates, and n-pentanoate mixed salts, respectively. The thermotropic liquid
      crystal of the thallium(I) n-pentanoate transforms into a more stable liquid
      crystal phase, which appears in the phase diagram between 380 and 488 K and for x
      = 0 up to x = 0.56. The crystal structure of thallium(I) propanoate and of the
      two mixed salts were obtained via X-ray synchrotron radiation diffraction
      measurements. These compounds present a bilayered structure similar to the two
      pure lithium salts previously found by our group.

PMID- 20684632
TI  - Characterization of perfluorooctylbromide-based nanoemulsion particles using
      atomistic molecular dynamics simulations.
AB  - Perfluorocarbon-based nanoemulsion particles have arisen as promising platforms
      for the cellular delivery of imaging and therapeutic agents to specific targets.
      However, current knowledge of the agent delivery mechanism is limited to
      qualitative and phenomenological models. Lack of detail at the molecular level
      has hence delayed optimizing or customizing nanoemulsion particles for
      therapeutic and imaging applications. Here we report the first atomistic
      structural details of a perfluorooctylbromide-based (PFOB-based) nanoemulsion
      particle (NEP) with a 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC) lipid
      emulsifier. Newly developed PFOB force-field parameters were used in molecular
      dynamics simulations to model the PFOB-NEP interface in a planar configuration.
      These PFOB force field parameters were developed and tested to reproduce the
      characteristics of bulk PFOB as well as PFOB at interfaces with water and
      emulsifying phospholipids. The modeled PFOB-NEP interface demonstrated
      significant intercalation of PFOB into the emulsifying lipid monolayer and
      consequent changes in the structural, electrostatic, and mechanical properties of
      the POPC monolayer and PFOB. This intercalation provides an explanation for
      experimental data demonstrating melittin tryptophan fluorescence quenching upon
      binding to the nanoemulsion particles through the observation of direct contact
      between the melittin tryptophan and the PFOB bromine. Additionally, the atomistic
      details of the PFOB-NEP interface structure provided by our simulations are used
      to suggest the influence of each component on PFOB-NEP delivery function which
      will be tested in future coarse-grained simulations.

PMID- 20684634
TI  - Electrophoresis of a soft particle within a cylindrical pore: polarization effect
      with the nonlinear Poisson-Boltzmann equation.
AB  - Electrophoresis of a soft particle along the centerline of a cylindrical pore is
      investigated theoretically in this study. The soft particle consists of an inner
      hard sphere covered by a concentric porous layer with fixed charge uniformly
      distributed in it. The polarization effect, the deformation of ion clouds
      surrounding the particle due to convection flow, is taken into account properly
      by adopting the full nonlinear Poisson-Boltzmann equation. The study reveals that
      recent investigation in the literature without consideration of the polarization
      effect could severely overestimate the particle mobility up to nearly two times
      if the fixed charge in the porous layer is high. The boundary effect in terms of
      the reduction of particle mobility is very significant when the double layer is
      thick and diminishes as it gets very thin. The effect of the highly charged
      cylindrical wall is analyzed, in particular, among other factors of
      electrokinetic interest. The presence of the cylindrical wall retards the
      particle motion in general, as compared with an isolated particle. With the
      generation of an electroosmotic flow, however, the charged wall can either
      enhance the particle motion or deter it, depending on the surface potential on
      the wall and the double-layer thickness. The thinner the double layer, the more
      significant the influence of the osmotic flow on the particle motion in general.
      The direction of particle motion may even change twice as the reciprocal of the
      double-layer thickness increases when both the wall and the particle are highly
      charged. This is due to the competition between the electric driving force of the
      charged particle and the hydrodynamic retarding force from the background
      electroosmotic flow. This has direct impact in practical applications of
      nanofluidics when a weak electric field is applied. Conducting operations near
      these critical double-layer thicknesses should be avoided in practice.

PMID- 20684636
TI  - A force field for 3,3,3-fluoro-1-propenes, including HFO-1234yf.
AB  - The European Union (EU) legislation 2006/40/EC bans from January 2011 the
      cooperative marketing of new car types that use refrigerants in their heating,
      ventilation, and air conditioning (HVAC) systems with global warming potentials
      (GWP) higher than 150. Thus, the phase-out of the presently used
      tetrafluoroethane refrigerant R134a necessitates the adoption of alternative
      refrigerants. Fluoropropenes such as 2,3,3,3-tetrafluoro-1-propene (HFO-1234yf)
      are currently regarded as promising low GWP refrigerants, but the lack of
      experimental data on their thermophysical properties hampers independent studies
      on their performance in HVAC systems or in other technical applications. In
      principle, molecular modeling can be used to predict the relevant properties of
      refrigerants, but adequate intermolecular potential functions ("force fields")
      are lacking for fluoropropenes. Thus, we developed a transferable force field for
      fluoropropenes composed of CF(3)-, -CF=, -CH=, CF(2)=, and CH(2)= groups and
      applied the force field to study 3,3,3 trifluoro-1-propene (HFO-1243zf), 2,3,3,3
      tetrafluoro-1-propene (HFO-1234yf), and hexafluoro-1-propene (HFO-1216). We
      performed Gibbs ensemble simulations on these three fluoropropenes to compute the
      vapor pressure, saturated densities, and heats of vaporization. In addition,
      molecular dynamics simulations were conducted to provide predictions for the
      density, thermal expansivity, isobaric heat capacity, and transport properties of
      liquid HFO-1234yf in the temperature range from 263.15 to 310 K and pressures up
      to 2 MPa. Agreement between simulation results and experimental data and/or
      correlations (when available) was good, thereby validating the predictive ability
      of the force field.

PMID- 20684635
TI  - How wall curvature affects the structure of fluid around a cylindrical
      nanoparticle: a DFT approach.
AB  - In this work, the perturbative fundamental measure theory has been employed to
      obtain the two-dimensional density distributions of the two hard-sphere and hard
      core Two-Yukawa fluids around a hard cylindrical nanoparticle. We have performed
      our calculations for different densities and temperatures. It has been observed
      that the oscillatory behavior of structure of molecules around a cylindrical
      nanoparticle increases with density and with decreasing wall curvature. In fact,
      energy and entropy effects determine fluid structure around the cylindrical
      nanoparticle. Our results show that, in the absence of any long-range wall
      molecule and molecule-molecule interactions, hard-sphere-hard-wall, the effect of
      wall curvature on structure is determined by entropy effects. In this case,
      molecules show a reduced tendency to accumulate at the wall with increasing
      curvature and a minimal tendency to position themselves at the nanoparticle
      edges. Energy effects in fluids with molecule-molecule attractions, Yukawa
      fluids, may lead to an increase in the tendency of their molecules to accumulate
      at more curved walls. In these systems, the competition between energy and
      entropy effects may reverse their molecular behavior such that they have the
      greatest tendency to accumulate at the edges rather than at other regions. Cases
      have been observed in which the domination of energy effects causes the depletion
      phenomenon near the walls. In this study, these observations have been confirmed
      by studying the local excess adsorptions around different regions of a
      cylindrical nanoparticle.

PMID- 20684633
TI  - Acyl-chain mismatch driven superlattice arrangements in DPPC/DLPC/cholesterol
      bilayers.
AB  - Fluorescence and infrared spectroscopy and cholesterol oxidase activity were
      employed to investigate the effect of phosphatidylcholine (PC) acyl chain length
      mismatch on the lateral organizations of lipids in liquid-ordered dipalmitoyl
      PC/dilauroyl-PC/cholesterol (DPPC/DLPC/CHOL) bilayers. Plots of steady-state
      fluorescence emission anisotropy of diphenylhexatriene (DPH) labeled PC (DPH-PC)
      embedded in the DPPC/DLPC/CHOL bilayers revealed significant peaks at several
      DPPC mole fractions (Y(DPPC)) when the cholesterol mole fraction (X(CHOL)) was
      fixed to particular values. Analogously, the DPH-PC anisotropy peaked at several
      critical X(CHOL)'s when Y(DPPC) was fixed. Acyl chain C-H and C horizontal lineO
      vibrational peak frequencies of native PC as well as the activity of cholesterol
      oxidase also revealed dips and peaks at similar Y(DPPC)'s. Importantly, most of
      the observed peaks/dips coincide with the critical mole fractions predicted by
      the Superlattice (SL) model. A three-dimensional map of DPH-PC anisotropy versus
      composition in the range 0.32 <or= X(CHOL) <or= 0.50; 0.54 <or= Y(DPPC) <or= 0.72
      revealed a prominent peak at (X(CHOL), Y(DPPC)) approximately (0.42, 0.64). This
      suggests a simultaneous presence of two different types of superlattices, one
      where cholesterol is the quest molecule in a PC host lattice and another where
      DPPC is the guest in the DLPC host lattice. Time-resolved measurements of DPH-PC
      fluorescence indicated the existence of an ordered, rotationally hindered
      environment of acyl chains at that "critical" composition consistent with the
      existence of SL arrangements. We propose that beside CHOL/PC superlattices, DPPC,
      and DLPC as well tend to adopt regular SL-like lateral distributions relative to
      each other, presumably because the less hydrophobic DLPC molecule is slightly
      displaced toward the aqueous phase, thus allowing more room and mobility for the
      head groups of both DPPC and DLPC as well as for the acyl chain tails of DPPC.
      The parallel presence of two kinds of superlattices, that is, CHOL/PC-SL and
      DPPC/DLPC-SL as demonstrated here, has intriguing implications regarding lipid
      homeostasis of eukaryote membranes.

PMID- 20684637
TI  - Ion rejection properties of nanopores with bipolar fixed charge distributions.
AB  - Ion rejection properties of cylindrical nanopores with bipolar fixed charge
      distributions have been investigated theoretically by means of an approximate
      model based on the Poisson-Nernst-Planck (PNP) theory and accounting for the
      electroosmosis phenomenon. The approximate model has been shown to give results
      that are in good agreement with the full 2D PNP approach for the narrow and
      weakly charged pores considered in this work. Pressure-induced rectification of
      salt flux has been put in evidence as a result of the broken symmetry of the
      fixed charge distribution on the pore walls. The model also elucidates that
      pressure-induced transport is controlled by different pore regions depending on
      the magnitude of the pressure difference across the nanopore. The existence of an
      optimal pressure difference (i.e., leading to the highest salt rejection) has
      been put in evidence when there is a region within the nanopore that is more
      repulsive than the pore entrance with respect to a given electrolyte. For
      moderate pressure differences, our results show that nanopores with bipolar
      charge distributions can lead to close rejections for both 2-1 and 1-2 asymmetric
      electrolytes. This is a specific property of bipolar nanopores because these
      performances cannot be obtained with homogeneously charged nanopores, which
      strongly reject electrolytes with divalent co-ions but are much more permeable to
      electrolytes with divalent counterions. This work benefits the design of
      nanoporous systems with targeted distribution of ionizable surface groups for
      advanced membrane separations.

PMID- 20684638
TI  - Agent-based modeling for the 2D molecular self-organization of realistic
      molecules.
AB  - We extend our previously developed agent-based (AB) algorithm to the study of the
      self-assembly of a fully atomistic model of experimental interest. We study the
      2D self-assembly of a rigid organic molecule (1,4-benzene-dicarboxylic acid or
      TPA), comparing the AB results with Monte Carlo (MC) and MC simulated annealing,
      a technique traditionally used to solve the global minimization problem. The AB
      algorithm gives a lower energy configuration in the same simulation time than
      both of the MC simulation techniques. We also show how the AB algorithm can be
      used as a part of the protocol to calculate the phase diagram with less
      computational effort than standard techniques.

PMID- 20684639
TI  - MD study of solvation in the mixture of a room-temperature ionic liquid and
      CO(2).
AB  - Solvation structure and dynamics of a saturated solution of carbon dioxide in the
      room-temperature ionic liquid 1-butyl-3-methylimidazolium hexafluorophosphate
      (BMI+PF6-) at 313 K and 0.15 kbar are investigated via molecular dynamics
      computer simulations by employing a diatomic probe solute. It is found that the
      mixture shows preferential solvation, which is mainly controlled by the solute
      BMI+PF6- electrostatic interactions and thus dictates differing roles for CO2 as
      the solute charge distribution varies. The local structure and density of BMI+PF6
      and CO2 in the vicinity of the solute become enhanced and reduced, respectively,
      as its dipole moment increases. As a result, equilibrium solvation dynamics of a
      nonpolar solute in the mixture have a strong CO2 character, whereas those of a
      dipolar solute are very similar to, albeit faster than, solvation dynamics in
      pure BMI+PF6-. Related nonequilibrium solvent response couched in dynamic Stokes
      shifts and accompanying solvation structure relaxation, in particular, CO2
      structure reorganization, shows interesting dependence on the solute charge
      distribution. Ion transport in the mixture is much faster than in pure BMI+PF6-,
      indicating that the addition of cosolvent CO2 reduces the viscosity of the ionic
      liquid, significantly. The effective polarity of the mixture, measured as
      solvation-induced stabilization of a dipolar solute, is found to be comparable to
      that of neat BMI+PF6-, consonant with solvatochromic measurements.

PMID- 20684640
TI  - Amino acid behavior in aqueous denaturant solutions: temperature dependence of
      the L-histidine-amide interaction.
AB  - We have studied the thermodynamics of the pair interaction between aromatic amino
      acid-l-histidine and nonelectrolyte denaturing globular proteins-hydrophilic urea
      (U) and presumably hydrophobic dimethylformamide (DMF) in the temperature range
      of 288-328 K. Our study does indicate for the first time the anomalous
      temperature dependence of the enthalpies and entropies of the l-histidine-U and l
      histidine-DMF interaction in water, which is consistent with the previously
      reported results for water-urea (U) and water-U-l-phenylalanine systems. This
      phenomenon is found to be closely related to the behavior of water, since in all
      cases, the extrema observed arise in the temperature range of 300-308 K, where
      the temperature dependence of the heat capacity of pure water passes through the
      minimum. The amino acid-urea interaction is shown to be accompanied in a wide
      temperature range by a large negative enthalpy change, which reveals a strong
      tendency of urea binding with polar and charged groups of proteins.

PMID- 20684641
TI  - pH-Dependent interactions of human islet amyloid polypeptide segments with
      insulin studied by replica exchange molecular dynamics simulations.
AB  - Amyloidogenesis of human islet amyloid polypeptide (hIAPP) within or surrounding
      secretory beta-cells of pancreas has long been related to the pathology of type
      II diabetes. Insulin, coexpressed and cosecreted with hIAPP in vivo, has the
      capacity of interacting with hIAPP and further inhibiting the amyloid deposition
      of the peptide. On the basis of the reported experimental data, we conducted
      replica exchange molecular dynamics simulations on the complexes of insulin and
      the binding segment 9-20 of rat/human IAPP under different pH values. The
      deprotonation of H18 at neutral pH reduces the possibility of polar interactions
      at position 18 as well as the flanking positions. Moreover, it destabilizes the
      helical motif of insulin-bound hIAPP. From several perspectives, hIAPP with
      charged H18 bears more resemblance to rat IAPP (rIAPP) with a point mutation of
      R18 than its neutral version does. It is likely that the positively charged
      residue at position 18 is critical to insulin binding. At neutral pH, three
      loosely binding sites can be recognized on the insulin surface, while at acidic
      pH one dominant binding site is resolved, which is similar to the previously
      identified rIAPP-insulin binding site. Several critical intermolecular contacts,
      including salt-bridges and pi-stacking interactions, identified in the current
      study, could be used as the starting point for devising a potent peptide
      inhibitor of hIAPP amyloidogenesis.

PMID- 20684642
TI  - Label-free in situ SERS imaging of biofilms.
AB  - Surface-enhanced Raman scattering (SERS) is a promising technique for the
      chemical characterization of biological systems. It yields highly informative
      spectra, can be applied directly in aqueous environment, and has high sensitivity
      in comparison with normal Raman spectroscopy. Moreover, SERS imaging can provide
      chemical information with spatial resolution in the micrometer range (chemical
      imaging). In this paper, we report for the first time on the application of SERS
      for in situ, label-free imaging of biofilms and demonstrate the suitability of
      this technique for the characterization of the complex biomatrix. Biofilms, being
      communities of microorganisms embedded in a matrix of extracellular polymeric
      substances (EPS), represent the predominant mode of microbial life. Knowledge of
      the chemical composition and the structure of the biofilm matrix is important in
      different fields, e.g., medicine, biology, and industrial processes. We used
      colloidal silver nanoparticles for the in situ SERS analysis. Good SERS
      measurement reproducibility, along with a significant enhancement of Raman
      signals by SERS (>10(4)) and highly informative SERS signature, enables rapid
      SERS imaging (1 s for a single spectrum) of the biofilm matrix. Altogether, this
      work illustrates the potential of SERS for biofilm analysis, including the
      detection of different constituents and the determination of their distribution
      in a biofilm even at low biomass concentration.

PMID- 20684643
TI  - Charge separation and photosensitized damage in DNA mediated by naphthalimide,
      naphthaldiimide, and anthraquinone.
AB  - Charge-separation and charge-recombination dynamics and oxidative DNA degradation
      were investigated for DNA modified with a photosensitizer (Sens) naphthalimide
      (NI), naphthaldiimide (ND), or anthraquinone (AQ). In all three Sens-modified DNA
      systems, the formation of long-lived charge-separated states was observed in
      which the lifetime increased with increasing numbers of A-T base pairs between
      Sens and the neighboring G-C base pair. The lifetime of the charge-separated
      state correlated well with the DNA damage yield, indicating that the charge
      separated state provides time for the irreversible DNA oxidative damage to occur.
      The quantum yield of DNA damage was the lowest for ND-modified DNA due to the
      slow reaction of ND radical anion with molecular oxygen; the process needed to
      preclude charge recombination. The AQ-modified DNA resulted in the highest charge
      separation and subsequent DNA damage yield, which would be partly explained by
      the formation of the spin-forbidden triplet radical ion pairs during charge
      separation.

PMID- 20684645
TI  - (2)H NMR study of the water dynamics in hydrated myoglobin.
AB  - We use 1D and 2D (2)H NMR to study the temperature-dependent mechanism for the
      rotational motion of myoglobin hydration water. The results show that isotropic
      and anisotropic water reorientation is observed at high and low temperatures,
      respectively, with a continuous crossover in the temperature range of 200-230 K.
      The anisotropic low-temperature motion has a large angular amplitude. It exhibits
      a broad distribution of geometries and pronounced dynamical heterogeneities,
      which are long-lived at least at T approximately 176 K. Exploiting the
      possibility to vary the angular resolution of (2)H NMR experiments, we find that
      the large solid angle accessible to low-temperature water reorientation is
      explored via large-angle rather than small-angle elementary steps; i.e., the
      rotational motion is not diffusive. Quantitative analysis of the NMR data using
      random-walk simulations implies that the number of sites involved in the observed
      water reorientation decreases from an infinite number during essentially
      isotropic motion above 230 K to a few, possibly two, below 165 K. Although the
      changes in the mechanism for water rotational motion may be accompanied by a mild
      change in the temperature dependence of the rotational correlation times, the
      (2)H NMR data provide strong evidence against the existence of a sharp fragile-to
      strong transition at about 225 K. The present results are discussed in the
      context of previous experimental findings for hydrated proteins.

PMID- 20684644
TI  - Molecular orientation in dry and hydrated cellulose fibers: a coherent anti
      Stokes Raman scattering microscopy study.
AB  - Coherent anti-Stokes Raman scattering (CARS) microscopy is combined with
      spontaneous Raman scattering microspectroscopy and second harmonic generation
      (SHG) microscopy to interrogate the molecular alignment in dry and hydrated
      cellulose fibers. Two types of cellulose were investigated: natural cellulose I
      in cotton fibers and regenerated cellulose II in rayon fibers. On the basis of
      the orientation of the methylene symmetric stretching vibration, the molecular
      alignment of cellulose microfibrils is found to be conserved on the micrometer
      scale. Whereas the molecular orientation in cotton shows modest variability along
      the fiber, the alignment of the cellulose units in rayon is highly consistent
      throughout the fiber. The ordered alignment is retained upon fiber hydration.
      Upon hydration of the cellulose fibers, an anisotropic electronic contribution is
      observed, which indicates an ordered incorporation of water molecules into the
      fiber structure. The third-order and second-order electronic polarizability of
      cellulose I are directed along the axis of the polyglucan chain. No second-order
      optical response is observed in cellulose II, supporting the antiparallel
      arrangement of the polyglucan chains in regenerated cellulose.

PMID- 20684646
TI  - Mutual relationship between stacking and hydrogen bonding in DNA. Theoretical
      study of guanine-cytosine, guanine-5-methylcytosine, and their dimers.
AB  - The mutual relationship between stacking and hydrogen-bonding and the possible
      influence of stacking in the different behavior of cytosine (C) and 5
      methylcytosine (C') in DNA have been studied through complete DFT optimization of
      different structures of G-C and G-C' dimers (i.e., G-C/C-G and G-C'/C'-G), using
      four different functionals. Our results show that stacking leads to an increase
      of the O(6)...H-N(4) hydrogen bond length and to a simultaneous decrease of the
      N(2)-H...O(2) one, in such a way that both lengths approach each other and, in
      some cases, an inversion occurs. These results suggest that stacking can be a
      factor to explain the disparity between theory and experiment on the relative
      strength of the two lateral hydrogen bonds. Regarding the difference between
      cytosine and 5-methylcytosine, we have shown that methylation enhances the
      stacking interactions, mainly due to the increase of polarizability. Methylation
      also favors the existence of slid structures which can produce local distortions
      of DNA.

PMID- 20684647
TI  - Fibrillation in human serum albumin is enhanced in the presence of copper(II).
AB  - The aggregation process in proteins is governed by several factors such as
      temperature, pH, presence of electrolytes, denaturants, and metal ions. Here, we
      report the role of Cu(II) in inducing rapid fibrillation in human serum albumin.
      We have monitored this process via UV-vis spectroscopy, fluorescence
      spectroscopy, circular dichroism, zeta-potential measurements, electron
      paramagnetic resonance studies, fluorescence microscopy, and field emission
      scanning electron microscopy. Images show a fibrillar network of human serum
      albumin in the presence of Cu(II) in 60% ethanol incubated at 65 degrees C at
      physiological pH. All other studies also support the enhanced fibrillation in
      presence of Cu(II).

PMID- 20684651
TI  - The concept of spectral accuracy for MS.
AB  - Though MS has always appeared to be quite different from spectroscopy to
      analytical chemists who are familiar with both, a careful examination from
      historical and theoretical perspectives reveals a striking similarity between the
      two. With the introduction of spectral accuracy, a companion concept to the
      better known mass accuracy, new capabilities previously thought unfeasible can
      now be enabled for MS. (To listen to a podcast about this article, please go to
      the Analytical Chemistry multimedia page at
      pubs.acs.org/page/ancham/audio/index.html .).

PMID- 20684652
TI  - Proteomic and phosphoproteomic analysis at diapause initiation in the cotton
      bollworm, Helicoverpa armigera.
AB  - Diapause is a period of developmental arrest that allows a species to adapt to
      unfavorable conditions. Many insect species reduce metabolic activity and then
      enter diapause at a certain stage in their life cycles. The cotton bollworm,
      Helicoverpa armigera, will be destined for pupal diapause when larvae are reared
      under short daylengths and low temperature. The brain is an important organ for
      diapause decision, and some signaling molecules from the brain of diapause
      destined individuals are released into the hemolymph to regulate diapause. In
      this study, we performed 2-D gel-based comparative proteomic and phosphoproteomic
      analyses to search for differentially expressed proteins between nondiapause- and
      diapause-destined pupal brains. A total of 79 proteins and 23 phosphoproteins
      showed significant differences between these two groups, and 41 proteins and 10
      phosphoproteins were identified by MALDI-TOF/TOF MS. Further, gene expression
      patterns in diapause- and nondiapause-destined pupal brains were confirmed by RT
      PCR or Western blot analysis. These differentially expressed proteins act in the
      metabolic change, stress response, and signal transduction pathways at early
      pupal stage for diapause initiation. Thus, these identified proteins may depress
      metabolism in diapause-destined pupae to lead the insect to enter developmental
      arrest.

PMID- 20684653
TI  - Enhanced Eu3+ emission in aqueous phosphotungstate colloidal systems:
      stabilization of polyoxometalate nanostructures.
AB  - Luminescent Eu(3+)-containing polyphosphate-tungstate aqueous colloidal systems
      were prepared and studied as a function of the relative polyphosphate-tungstate
      content. In polyphosphate-rich solutions, Eu(3+) ions occupy cagelike sites
      composed of phosphate groups from the metaphosphate chains. In these sites, an
      average number of 0.5 water molecule coordinates to an Eu(3+) ion and the (5)D(0)
      emission quantum efficiency is 0.22. Tungstate addition leads to important
      modifications in neighboring Eu(3+) leading to coordination sites in the aqueous
      medium where metal ions are completely hidden from interactions with solvent
      molecules. Transmission electron microscopy results clearly show W-rich
      nanoparticles with sizes between 5 and 10 nm for all tungstate relative
      concentrations. For high tungstate relative contents (above 30 mol %),
      spectroscopic results suggest the presence of Eu(3+) in polyoxometalate (POM)
      like sites by comparison with the well-known decatungstoeuropate [EuW(10)O(36)](9
      ) structure. These new aqueous colloids display surprisingly high (5)D(0)
      emission quantum efficiencies of ca 80% because of the strong ligand field
      provided by tungstate POM ligands and the complete absence of water molecules
      from the Eu(3+) first coordination shell.

PMID- 20684654
TI  - First-principles calculation of electron spin-rotation tensors.
AB  - Using Curl's Hamiltonian (Curl, R. F. Mol. Phys. 1965, 9, 585) first-principles
      calculations at the Hartree-Fock and various coupled-cluster (CC) levels based on
      a perturbative scheme are reported. The effects of basis-set dependence and
      electron correlation have been investigated by performing benchmark calculations
      for a set of radicals comprising 12 species and 14 electronic states. In
      comparison to experimental results, the electron spin-rotation tensor is obtained
      with a 10-15% accuracy when using the CC singles and doubles approximation and a
      triple-zeta quality basis set. Some improvements are seen when triple excitations
      are considered via the CC singles, doubles, and triples model.

PMID- 20684655
TI  - Thermal diffusion of oligosaccharide solutions: the role of chain length and
      structure.
AB  - We investigated the chain length dependence of the thermodiffusion behavior of
      oligosaccharides by the infrared thermal diffusion forced Rayleigh scattering (IR
      TDFRS) technique. Three disaccharides, sucrose, cellobiose and maltose, two
      trisaccharides, melezitose and raffinose, and a tetrasaccharide, stachyose, have
      been studied. We determined the thermal diffusion (D(T)), mass diffusion (D), and
      Soret (S(T)) coefficient as a function of temperature and concentration. While
      monosaccharides in water accumulate at the cold side in the investigated
      temperature (20-50 degrees C) and concentration (0.2-0.6667 wt) range,
      oligosaccharides enrich on the warm side with decreasing temperature or
      increasing sugar concentration. Additionally, we determined the kinematic
      viscosity (nu), the density (rho), and the thermal expansion coefficient (alpha)
      of the mixtures in order to check the linear correlation between D(T) and the
      ratio alpha/nu, which has been recently found for aqueous solutions of
      monosaccharides and for alkane mixtures. Finally, we found that D(T) and D decay
      with increasing chain length of the oligosaccharides in the whole studied range
      of temperatures, in contradiction with experimental results for nonpolar mixtures
      and theoretical predictions.

PMID- 20684656
TI  - Analysis of enhanced pharmacy services in rural community pharmacies in Western
      Australia.
AB  - INTRODUCTION: Enhanced pharmacy services (EPS) are health related services above
      those normally available with the supply of medicines. Rural pharmacies could
      provide a diversity of EPS in response to the limited access and reduced health
      services available in rural areas. The objective of this study was to evaluate
      the provision of EPS in rural Western Australian (WA) pharmacies in 2006,
      compared with findings extracted from a national survey conducted in 2002.
      Barriers to and facilitators for the provision of ETS in rural settings were also
      analysed. METHODS: The survey was conducted in 2006, using a questionnaire
      developed from a 2002 Australian national survey questionnaire. The
      questionnaires were mailed to all 103 pharmacies in rural WA and 51 were returned
      (49.5%). Chi-squared tests were used to test associations between year of survey
      and provision of each EPS. Where significant associations were reported, logistic
      regression analyses that controlled for sex, age, PhARIA location (remoteness),
      and inclusion of a forward pharmacy area were performed. RESULTS: The WA rural
      pharmacies offered a range of EPS. There were marked increases in weight testing
      and weight management services. The availability of smoking cessation services
      increased from 52% of rural pharmacies in 2002 to 63% in 2006. Other EPS (asthma,
      diabetes, hypertension, hyperlipidaemia), which correspond to the Australian
      Government National Health Priorities Areas were offered by 20% to 50% of
      pharmacies and had not increased between surveys. A continued shortage in the
      pharmacist workforce was a major barrier to EPS provision. CONCLUSIONS: Provision
      of EPS in rural pharmacies is more important than in metropolitan pharmacies
      because there is often a lack of other sources for these services in rural and
      remote locations. A range of defined EPS were provided by 25% to 60% of rural and
      remote pharmacies, with other services offered in lower percentages. Significant
      increases were found in some important EPS, such as weight management. Additional
      support for EPS provision in rural and remote communities is required to increase
      uptake among pharmacists. Government and pharmacy bodies need to implement rural
      practice models to address identified pharmacist workforce barriers and improve
      access to EPS to rural communities.

PMID- 20684658
TI  - Distinct defenses induced in wheat against powdery mildew by acetylated and
      nonacetylated oligogalacturonides.
AB  - In wheat, little is known about disease resistance inducers and, more
      specifically, about the biological activities from those derived from endogenous
      elicitors, such as oligogalacturonides (OGAs). Therefore, we tested the ability
      of two fractions of OGAs, with polymerization degrees (DPs) of 2-25, to induce
      resistance to Blumeria graminis f. sp. tritici and defense responses in wheat.
      One fraction was unacetylated (OGAs-Ac) whereas the second one was 30% chemically
      acetylated (OGAs+Ac). Infection level was reduced to 57 and 58% relative to
      controls when OGAs-Ac and OGAs+Ac, respectively, were sprayed 48 h before
      inoculation. Activities of various defense-related enzymes were then assayed in
      noninoculated wheat leaves infiltrated with OGAs. Oxalate oxidase, peroxidase,
      and lipoxygenase were responsive to both OGAs-Ac and OGAs+Ac, which suggests
      involvement of reactive oxygen species and oxilipins in OGAs-mediated responses
      in wheat. In inoculated leaves, both fractions induced a similar increase in H2O2
      accumulation at the site of fungal penetration. However, only OGAs+Ac led to an
      increase in papilla-associated fluorescence and to a reduction of formed fungal
      haustoria. Our work provides the first evidence for elicitation and protection
      effects of preventive treatments with OGAs in wheat and for new properties of
      acetylated OGAs.

PMID- 20684659
TI  - Blood pressure variability: Emerging role in risk assessment and therapeutics.

PMID- 20684660
TI  - Re-evaluating dissociations between implicit and explicit category learning: an
      event-related fMRI study.
AB  - Recent fMRI studies have found that distinct neural systems may mediate
      perceptual category learning under implicit and explicit learning conditions. In
      these previous studies, however, different stimulus-encoding processes may have
      been associated with implicit versus explicit learning. The present design was
      aimed at decoupling the influence of these factors on the recruitment of
      alternate neural systems. Consistent with previous reports, following incidental
      learning in a dot-pattern classification task, participants showed decreased
      neural activity in occipital visual cortex (extrastriate region V3, BA 19) in
      response to novel exemplars of a studied category compared to members of a foil
      category, but did not show this decreased neural activity following explicit
      learning. Crucially, however, our results show that this pattern was primarily
      modulated by aspects of the stimulus-encoding instructions provided at the time
      of study. In particular, when participants in an implicit learning condition were
      encouraged to evaluate the overall shape and configuration of the stimuli during
      study, we failed to find the pattern of brain activity that has been taken to be
      a signature of implicit learning, suggesting that activity in this area does not
      uniquely reflect implicit memory for perceptual categories but instead may
      reflect aspects of processing or perceptual encoding strategies.

PMID- 20684662
TI  - Nonsyndromic multiple basal cell carcinomas successfully treated with imiquimod
      5% cream.
AB  - This report describes the case of a 60-year-old man with nonsyndromic multiple
      basal cell carcinomas that responded to imiquimod 5% cream. The patient had no
      additional anomalies suggesting any syndromes associated with multiple basal cell
      carcinomas. By applying the agent 5 times a week for 20 weeks, we obtained good
      clinical results, and we confirmed the improvement with histopathologic
      examination. We suggest that patients with multiple basal cell carcinomas should
      be interviewed about and tested for the associated syndromes, and topical
      imiquimod should be kept in mind as an alternative therapy choice in these
      patients.

PMID- 20684663
TI  - A nuclear receptor, hepatocyte nuclear factor 4, differently contributes to the
      human and mouse angiotensinogen promoter activities.
AB  - Angiotensinogen (AGT), mainly produced in the liver, is the precursor of
      angiotensin II, an important regulator of blood pressure and electrolyte
      homeostasis. We previously showed, in hepatoma-derived HepG2 cells that a
      hepatocyte nuclear factor 4 (HNF4) potentiated human AGT (hAGT) promoter activity
      and identified its binding sites (termed regions C and J) in the hAGT promoter
      region. We also showed in transgenic mouse (TgM) that the hAGT is abundantly
      expressed in the kidney where the level of endogenous mouse AGT (mAGT) expression
      is low. To elucidate molecular mechanisms of the AGT gene activation in the
      kidney, we first investigated the HNF4 and AGT expression in the mouse kidney.
      Northern blot, in situ hybridization and immunohistochemical analyses revealed
      that the hAGT and HNF4 were both expressed in the proximal tubular (PT) cells of
      the kidney. We then transfected the hAGT reporter constructs into immortalized
      mouse PT (mProx) cells and found that regions C and J contributed additively to
      the HNF4-potentiated hAGT promoter activity. Curiously, no obvious HNF4 binding
      motif was found in the corresponding region of the mAGT promoter and co
      transfected HNF4 failed to activate this promoter in neither HepG2 nor mProx
      cells. These results suggest that the high-level hAGT expression in the TgM
      kidney is, at least in part, due to a presence of high-affinity HNF4 binding
      sites in its promoter.

PMID- 20684661
TI  - Differential roles of frequency-following and frequency-doubling visual responses
      revealed by evoked neural harmonics.
AB  - Frequency-following and frequency-doubling neurons are ubiquitous in both striate
      and extrastriate visual areas. However, responses from these two types of neural
      populations have not been effectively compared in humans because previous EEG
      studies have not successfully dissociated responses from these populations. We
      devised a light-dark flicker stimulus that unambiguously distinguished these
      responses as reflected in the first and second harmonics in the steady-state
      visual evoked potentials. These harmonics revealed the spatial and functional
      segregation of frequency-following (the first harmonic) and frequency-doubling
      (the second harmonic) neural populations. Spatially, the first and second
      harmonics in steady-state visual evoked potentials exhibited divergent posterior
      scalp topographies for a broad range of EEG frequencies. The scalp maximum was
      medial for the first harmonic and contralateral for the second harmonic, a
      divergence not attributable to absolute response frequency. Functionally,
      voluntary visual-spatial attention strongly modulated the second harmonic but had
      negligible effects on the simultaneously elicited first harmonic. These
      dissociations suggest an intriguing possibility that frequency-following and
      frequency-doubling neural populations may contribute complementary functions to
      resolve the conflicting demands of attentional enhancement and signal fidelity-
      the frequency-doubling population may mediate substantial top-down signal
      modulation for attentional selection, whereas the frequency-following population
      may simultaneously preserve relatively undistorted sensory qualities regardless
      of the observer's cognitive state.

PMID- 20684664
TI  - A plaster containing DHEP and heparin for mild to moderate contusions and sprains
      with haematoma: a double-blind randomized study.
AB  - OBJECTIVE: This prospective, randomized, double-blind, three-arm study was
      performed to investigate the efficacy of a medicated plaster containing the
      combination of diclofenac epolamine (DHEP) 180 mg and heparin 5600 IU in the
      treatment of unilateral blunt soft tissue injuries involving the upper or lower
      limb, complicated by severe local haematoma. RESEARCH DESIGN AND METHODS:
      Patients with mild-to-moderate injuries complicated by local haematoma (< or =140
      cm(2)) were included and randomly treated once daily with plasters containing
      DHEP/heparin, DHEP only, or placebo. Plasters were applied for at least 12 hours
      daily for 10 consecutive days. MAIN OUTCOME MEASURES: The time to complete
      haematoma dissolution was the primary efficacy endpoint; secondary endpoints were
      spontaneous pain reduction, pain on movement, muscle swelling and use of rescue
      analgesia. RESULTS: A total of 185 patients (90 males and 95 females, aged 18-80
      years) were evaluated for efficacy. Baseline clinical and demographic
      characteristics were similar across the treatment groups. The time to complete
      haematoma dissolution was significantly shorter with the DHEP/heparin plaster
      compared with both the DHEP and placebo plasters (p < 0.05). Patients in the
      DHEP/heparin group had a 60% probability of achieving complete haematoma
      dissolution within the 10-day treatment period compared with patients receiving
      either DHEP or placebo plasters. Patient-rated reductions in pain on movement
      were significantly (p < 0.05) greater in the two active treatment groups compared
      with placebo. Overall, the DHEP/heparin, DHEP and placebo plasters were well
      tolerated. While a reliance on patient self-reporting had the potential to limit
      the usefulness of some data obtained in this study, the investigators accounted
      for this accordingly. CONCLUSIONS: The plaster formulation combining DHEP and
      heparin relieves pain and induces faster dissolution of superficial haematomas,
      and may therefore contribute to a more rapid and complete recovery.

PMID- 20684665
TI  - Effect of a plaster containing DHEP and heparin in acute ankle sprains with
      oedema: a randomized, double-blind, placebo-controlled, clinical study.
AB  - OBJECTIVE: Ankle sprains are the most frequent injuries in sport and daily life,
      and are usually treated with anti-inflammatory drugs or compounds that have an
      effect on microcirculation. The efficacy and tolerability of a novel plaster
      containing both diclofenac epolamine (DHEP) and heparin in the treatment of acute
      painful ankle sprains with oedema was investigated in a randomized, double-blind,
      placebo-controlled study. RESEARCH DESIGN AND METHODS: This study, carried out in
      32 French medical centres, enrolled 233 patients (148 male and 86 female, aged 18
      65 years) with an ankle sprain that had occurred within the previous 48 hours.
      Patients were treated once daily with DHEP heparin or placebo plaster for 7 days.
      MAIN OUTCOME MEASURES: Reduction in ankle joint swelling measured by submalleolar
      circumference was the primary efficacy endpoint; secondary endpoints were pain
      (at rest, in active mobilization, by passive stretch and by pressure), functional
      disability and global judgement of efficacy and tolerability. RESULTS: DHEP
      heparin-treated patients experienced a significantly greater reduction in joint
      swelling compared with placebo (p = 0.005). The reduction in pain was also in
      favour of DHEP heparin patients, with significantly lower pain in DHEP heparin
      treated than placebo-treated patients within 3 hours of the first application (p
      < 0.05). Only two patients in the DHEP heparin plaster group and six in the
      placebo group experienced minor adverse events, all of which resolved
      spontaneously. By design, the study was limited to a placebo-controlled
      comparison, and there was no test for possible selection bias (subsequently ruled
      out by choice of efficacy parameters and measures) that may have resulted in a
      baseline imbalance between patient groups. CONCLUSIONS: Results confirm the
      efficacy of DHEP heparin plaster compared with placebo for the treatment of
      painful ankle sprain with oedema. Prompt control of pain and oedema may shorten
      the time to initiation of a rehabilitation programme, thus reducing the risk of
      ankle disability recurrence and the development of chronic injury.

PMID- 20684667
TI  - The neurobiology of dopamine receptors: evolution from the dual concept to
      heterodimer complexes.
AB  - CONTEXT: G protein-coupled receptors (GPCRs) have been classically thought to
      work as monomeric entities. The current view of their organization, however,
      assumes that they are part of highly organized molecular complexes, where
      different receptors and interacting proteins are clustered. These heteromers have
      peculiar pharmacological, signaling, and trafficking properties. GPCR
      heteromerization, raising different combinatorial possibilities, thus underlies
      an unexpected level of diversity within this receptor family. METHODS: In this
      paper, we summarize recent data, reported by different research groups,
      suggesting that the dopamine (DA) D1 receptor forms heteromers with receptors of
      the same family and with structurally and functionally divergent receptors.
      RESULTS AND DISCUSSION: DA D1 and D3 receptors and glutamate NMDA receptors
      regulate rewarding mechanisms and motivated behavior, modulate emotional and
      cognitive processes and regulate locomotor activity by extensive cross-talk
      mechanisms. Co-localization of D1 and D3 receptors and D1 and NMDA receptors in
      specific neuronal populations in the striatum and nucleus accumbens, moreover,
      suggested that their cross-talk may involve direct interactions. By using
      different experimental approaches various groups have, in fact, demonstrated the
      existence of D1-NMDA and D1-D3 heteromers, in both transfected cell systems and
      in the straitum, with peculiar pharmacological, signaling, and functional
      properties. The putative role of the D1-D3 and D1-NMDA heteromers in the
      physiological regulation of striatal function and in the development of motor
      dysfunctions will be discussed.

PMID- 20684666
TI  - The changing world of G protein-coupled receptors: from monomers to dimers and
      receptor mosaics with allosteric receptor-receptor interactions.
AB  - Based on indications of direct physical interactions between neuropeptide and
      monoamine receptors in the early 1980s, the term receptor-receptor interactions
      was introduced and later on the term receptor heteromerization in the early
      1990s. Allosteric mechanisms allow an integrative activity to emerge either
      intramolecularly in G protein-coupled receptor (GPCR) monomers or
      intermolecularly via receptor-receptor interactions in GPCR homodimers,
      heterodimers, and receptor mosaics. Stable heteromers of Class A receptors may be
      formed that involve strong high energy arginine-phosphate electrostatic
      interactions. These receptor-receptor interactions markedly increase the
      repertoire of GPCR recognition, signaling and trafficking in which the minimal
      signaling unit in the GPCR homomers appears to be one receptor and one G protein.
      GPCR homomers and GPCR assemblies are not isolated but also directly interact
      with other proteins to form horizontal molecular networks at the plasma membrane.

PMID- 20684668
TI  - Regulation of M2, M3, and M4 muscarinic receptor expression in K562 chronic
      myelogenous leukemic cells by carbachol.
AB  - CONTEXT: Muscarinic receptors mediate a variety of cellular responses to
      acetylcholine, including inhibition of adenylate cyclase, breakdown of
      phosphoinositide and modulation of ion channels. These receptors are relatively
      abundant in the central nervous system and peripheral parasympathetic nervous
      system. Many cells express a mixture of muscarinic receptor transcripts. Changes
      in muscarinic M(2) and M(3) receptor mRNA levels in response to agonist treatment
      have been reported in cerebellar granule cells, Chinese hamster ovary cells,
      lymphocytes and in the human neuroblastoma cell line SH-SY5Y. OBJECTIVE: In this
      study, we investigated the effects of agonist stimulation on cell proliferation
      and on the levels of muscarinic receptor expression in K562 chronic myelogenous
      leukemia cells. METHODS: Total RNA and crude membrane fractions were prepared
      from K562 cells challenged with carbachol (CCh). Muscarinic receptor subtype
      expression was determined by RT-PCR and western blot analysis. Proliferation and
      cell viability were evaluated by the trypan blue exclusion test and BrDU
      labeling. RESULTS: We showed that CCh-treatment leads to changes in muscarinic
      M(2), M(3), and M(4) receptor transcripts as well as M(2) and M(3) protein
      levels. We also found that CCh decreased proliferation of K562 cells in a time
      dependent manner, an effect prevented by atropine. These results suggest that CCh
      modulates K562 chronic myelogenous leukemic cells proliferation through
      muscarinic acetylcholine receptors.

PMID- 20684669
TI  - Comparing healthcare costs of Medicaid patients with postherpetic neuralgia (PHN)
      treated with lidocaine patch 5% versus gabapentin or pregabalin.
AB  - OBJECTIVE: To compare healthcare resource utilization and costs of postherpetic
      neuralgia (PHN) patients initiating lidocaine patch 5% (lidocaine patch) or oral
      gabapentin/pregabalin. METHODS: Patients with PHN diagnosis, or herpes zoster
      diagnosis and >=30 days PHN-recommended treatment were selected from de
      identified Medicaid claims data from Florida, Iowa, Missouri, and New Jersey,
      1999-2007. Patients initiated monotherapy with lidocaine patch or
      gabapentin/pregabalin after PHN diagnosis, had continuous eligibility 6 months
      before (baseline) and 6 months after (study period) medication index date, and
      were >=18 years old. Lidocaine patch patients were matched to
      gabapentin/pregabalin patients based on their propensity to initiate treatment.
      Study period resource utilization and costs from a Medicaid perspective were
      compared between treatment groups using univariate analysis. RESULTS: Matched
      patients were on average 61.3 years old, approximately 73% were women, and 55%
      had other painful conditions during the baseline period. 6-month per patient PHN
      related prescription drug costs were similar for matched lidocaine patch (n=312)
      and gabapentin/pregabalin (n=312) patients ($854 vs. 820, p=0.75), while PHN
      related medical costs appeared lower in the lidocaine patch group ($145 vs. 353,
      p=0.12). Furthermore, there were no statistically significant differences between
      treatment groups during the observation period in overall resource utilization,
      total prescription drug costs, and total medical costs per patient. CONCLUSIONS:
      In spite of higher list prices, PHN patients treated with lidocaine patch cost no
      more than patients treated with gabapentin or pregabalin in terms of overall
      healthcare costs over the 6-month study period. The study suggests that PHN
      related medical costs may be lower among lidocaine patch patients. LIMITATIONS:
      Findings are based on a Medicaid sample and may not be generalizable to all PHN
      patients.

PMID- 20684670
TI  - Descriptive analysis of Medicaid patients with postherpetic neuralgia treated
      with lidocaine patch 5%.
AB  - OBJECTIVES: To compare demographic and comorbidity profiles and healthcare costs
      of Medicaid patients with postherpetic neuralgia (PHN) treated with lidocaine
      patch 5% (lidocaine patch) versus patients not treated with the lidocaine patch.
      Repeat comparison for the subset of patients treated in long-term care (LTC)
      settings. METHODS: Patients, age>=18 years, with PHN diagnosis, or PHN-likely
      patients with herpes zoster diagnosis and >=30 days of PHN-recommended treatment,
      were identified in Medicaid claims from Florida, Iowa, Missouri, and New Jersey
      (1999-2007). Patients had continuous eligibility 6 months before (baseline) and
      12 months after (study period) the PHN index date. Patients with >=1 claim for a
      lidocaine patch during the study period (n=872) were compared to patients without
      a lidocaine patch claim (comparison group). Baseline characteristics, study
      period treatment and healthcare costs (reimbursements by Medicaid for medical
      services and prescription drugs) were compared between groups using univariate
      analyses. RESULTS: PHN patients in the lidocaine patch group were older (64.5 vs.
      62.2 years; p=0.002) and had higher rates of pain-related comorbidities (e.g.,
      back/neck pain, osteoarthritis) than comparison patients. Average PHN-related
      drug costs per patient were higher ($1994 vs. 1137; p<0.0001) among lidocaine
      patch patients, with lidocaine patch accounting for $505 of the difference. PHN
      related medical costs appeared lower in the lidocaine patch group, although not
      statistically significant ($983 vs. 1294; p=0.1348). No significant differences
      were found in total healthcare costs ($20,175 vs. 19,124; p=0.3720) across
      groups, despite higher total prescription drug costs among lidocaine patch
      patients. A similar pattern was observed among LTC patients. CONCLUSIONS: Despite
      higher rates of comorbidities and prescription drug costs, lidocaine patch
      patients had similar study period healthcare costs as comparison patients. The
      cost of the lidocaine patch represented a small fraction of overall costs
      incurred over the study period. LIMITATIONS: Findings are based on a Medicaid
      sample and may not be generalizable to all PHN patients.

PMID- 20684671
TI  - Vibrating-mesh nebulization of liposomes generated using an ethanol-based
      proliposome technology.
AB  - This is the first study that evaluates the influence of the compartmental design
      of the micropump Aeroneb Go nebulizer and the viscosity of a proliposome
      hydration medium on vibrating-mesh aerosolization of liposomes. Ethanol-based
      proliposomes comprising soya phosphatidylcholine and cholesterol (1:1 mole ratio)
      were hydrated by using isotonic NaCl (0.9%) or sucrose (9.25%) solutions to
      generate liposomes that entrapped approximately 61% of the hydrophilic drug,
      salbutamol sulphate. Liposomes were aerosolized by the nebulizer to a two-stage
      impinger. For both formulations, the aerosol mass output was higher than the
      phospholipid output, indicating some accumulation of large liposomes or liposome
      aggregate within the nebulizer. Using NaCl (0.9%) solution as the dispersion
      medium, aerosol droplet size was much smaller and aerosol mass and phospholipid
      outputs were higher. This was attributed to the lower viscosity of the NaCl
      solution, resulting in a reduced retention of the aerosols in the "trap" of the
      nebulizer. For the entrapped salbutamol sulphate, although the "fine particle
      fraction" was relatively high (57.44%), size reduction of the liposomes during
      nebulization caused marked losses of the drug originally entrapped. Overall,
      liposomes generated from proliposomes when using this nebulizer showed high
      nebulization output and small droplet size. However, further work is required to
      reduce the losses of the originally entrapped drug from liposomes.

PMID- 20684672
TI  - Cerebral hemodynamic effects of acute hyperoxia and hyperventilation after severe
      traumatic brain injury.
AB  - The purpose of this study was to examine the effects of hyperventilation or
      hyperoxia on cerebral hemodynamic parameters over time in patients with severe
      traumatic brain injury (TBI). We prospectively studied 186 patients with severe
      TBI. CO2 and O2 reactivity tests were conducted twice a day on days 1-5 and once
      daily on days 6-10 after injury. During hyperventilation there was a significant
      decrease in intracranial pressure (ICP), mean arterial pressure (MAP), jugular
      venous oxygen saturation (Sjvo2), brain tissue Po2 (Pbto2), and flow velocity
      (FV). During hyperoxia there was an increase in Sjvo2 and Pbto2, and a small but
      consistent decrease in ICP, end-tidal carbon dioxide (etco2), partial arterial
      carbon dioxide pressure (Paco2), and FV. Brain tissue oxygen reactivity during
      the first 12 h after injury averaged 19.7 +/- 3.0%, and slowly decreased over the
      next 7 days. The autoregulatory index (ARI; normal = 5.3 +/- 1.3) averaged 2.2 +/
      1.5 on day 1 post-injury, and gradually improved over the 10 days of monitoring.
      The ARI significantly improved during hyperoxia, by an average of 0.4 +/- 1.8 on
      the left, and by 0.5 +/- 1.8 on the right. However, the change in ARI with
      hyperoxia was much smaller than that observed with hyperventilation.
      Hyperventilation increased ARI by an average of 1.3 +/- 1.9 on the left, and 1.5
      +/- 2.0 on the right. Pressure autoregulation, as assessed by dynamic testing,
      was impaired in these head-injured patients. Acute hyperoxia significantly
      improved pressure autoregulation, although the effect was smaller than that
      induced by hyperventilation. The very small change in Paco2 induced by hyperoxia
      does not appear to explain this finding. Rather, the vasoconstriction induced by
      acute hyperoxia may allow the cerebral vessels to respond better to transient
      hypotension. Further studies are needed to define the clinical significance of
      these observations.

PMID- 20684673
TI  - Pituitary function at long-term follow-up of childhood traumatic brain injury.
AB  - Pituitary dysfunction is a recognized sequela of traumatic brain injury (TBI),
      occurring in 10-83% of adult patients, but there are few data on the prevalence
      or natural history in childhood. Our objective was to determine pituitary
      function in children and young adults at least 4 years after TBI requiring
      pediatric intensive care unit (PICU) admission. The effects of TBI and
      hypopituitarism on height, adiposity, and quality of life (QOL) were also
      evaluated. Unselected patients discharged from the regional PICU with TBI (age <
      18 years at injury) from 1999-2004 were recruited. Blood and urine samples were
      collected for baseline pituitary function testing. Height and weight were
      measured. Adiposity was assessed by mid-upper arm and waist circumferences, and
      body fat percentage estimation using four-site skinfold thickness and
      bioelectrical impedance. Auxology and adiposity data were compared to local age-
      and sex-matched healthy control data. QOL questionnaires (PedsQL 4.0 and QOL
      AGHDA) were completed. Twenty subjects (median age 16.7 years, range 9.2-23.3
      years, 13 male) of 127 who were eligible agreed to participate at a median of 6.8
      years (range 4.2-10.3 years) since TBI. Markers of injury were higher in those
      recruited than those who were not. Biochemical evidence of hypopituitarism was
      identified in only one case, possibly related to comorbid pre-existing attention
      deficit-hyperactivity disorder. Height, weight, and adiposity were similar to
      healthy controls. Poor QOL was seen in patients with chronic functional deficits
      or comorbidities. Overall, pituitary dysfunction was less prevalent than in
      previous studies in adults and children. The results of this study do not support
      the use of routine endocrine evaluation of children following TBI.

PMID- 20684674
TI  - Liposome-encapsulated midazolam for oral administration.
AB  - The oral administration of midazolam has often been used for sedation in
      pediatric patients. However, oral administration of an intravenous formulation of
      midazolam is difficult for younger pediatric patients because of its bitter
      taste. Liposomes have been developed as vesicles encapsulating various kinds of
      drugs to serve as a medical drug-delivery system. Thus, the aim of the present
      study was to produce pH-sensitive liposomes encapsulating midazolam and to
      evaluate its pharmacokinetics on rabbits. Liposome-encapsulated midazolam was
      produced from hydrogenated L-alpha-phosphatidylcholine, cholesterol,
      dipalmitoylphosphatidic acid, and midazolam. The capacity of liposomes to
      encapsulate midazolam (encapsulation efficiency), stability of encapsulation, and
      release efficiency were evaluated in vitro. Further, the produced liposome
      encapsulated midazolam solution was orally administered to rabbits in vivo. As a
      result, midazolam was encapsulated by liposomes with a high encapsulation
      efficiency and was stably encapsulated in a physiological medium. Further, the
      produced liposomes rapidly and effectively released midazolam in an acidic medium
      in vitro. When the liposome-encapsulated midazolam solution was orally
      administered to rabbits, the time to achieve the maximum plasma concentration of
      midazolam after administration was slightly longer, but both the maximum plasma
      concentration and area under the concentration-time curve were higher than those
      receiving midazolam solution. In conclusion, we produced pH-sensitive liposome
      encapsulated midazolam, which remained stable in a physiological medium and
      showed efficient release in an acidic environment. The results suggest that it is
      possible to clinically use liposome-encapsulated midazolam for oral
      administration as a useful drug-delivery vehicle.

PMID- 20684675
TI  - Endothelin-1 is increased in cerebrospinal fluid and associated with unfavorable
      outcomes in children after severe traumatic brain injury.
AB  - Severe pediatric traumatic brain injury (TBI) is associated with unfavorable
      outcomes secondary to injury from activation of the inflammatory cascade, the
      release of excitotoxic neurotransmitters, and changes in the reactivity of
      cerebral vessels, causing ischemia. Hypoperfusion of injured brain tissues after
      TBI is also associated with unfavorable outcomes. Therapeutic hypothermia is an
      investigational treatment strategy for use in patients with severe TBI that has
      shown differential effects on various cerebrospinal fluid (CSF) mediators in
      pediatric patients. Endothelin-1 (ET-1) is a powerful vasoconstrictor that exerts
      its effects on the cerebrovascular endothelium for sustained periods after TBI.
      The purpose of this study was to determine if CSF concentrations of ET-1 are
      increased after severe TBI in children, and if they are associated with
      demographics and outcomes that are affected by therapeutic hypothermia. This was
      an ancillary study to a prospective, randomized-controlled trial of early
      hypothermia in a tertiary care pediatric intensive care unit. Children (n = 34,
      age 3 months-15 years) suffering from severe TBI were randomized to hypothermia
      (n = 19) and normothermia (n = 15) as part of the efficacy study. Children
      undergoing diagnostic lumbar puncture (n = 11) to rule out infection were used as
      controls. Patients received either mild to moderate hypothermia (32-33 degrees C)
      or normothermia as part of their treatment protocol. CSF was serially collected
      during the first 5 days after TBI. ET-1 concentrations were quantitated in
      patient and control CSF samples by a validated ELISA in duplicate with a limit of
      quantification of 0.195 pg/mL. CSF ET-1 concentrations were increased by two- to
      threefold in children after TBI compared to controls, and the increase was
      sustained for up to 5 days post-TBI. This relationship was not affected by
      hypothermia, and there were no differences in ET-1 response between children with
      inflicted and accidental TBI. Group-based trajectory analysis revealed two
      distinct groups with similar ET-1 levels over time. Univariate analysis showed a
      significant association between ET-1 levels and Glasgow Outcome Scale (GOS)
      scores, for which higher ET-1 levels over time were associated with unfavorable
      outcomes. ET-1 is increased in children with severe TBI and is associated with
      unfavorable outcomes. This increase in ET-1 may mediate the hypoperfusion or
      cerebrovascular dysfunction accompanying severe TBI in children. Importantly,
      hypothermia does not affect the brain's ET-1 response as measured in the CSF.

PMID- 20684676
TI  - Longitudinal characterization of motor and cognitive deficits in a model of
      penetrating ballistic-like brain injury.
AB  - Traumatic brain injury (TBI) produces a wide range of motor and cognitive
      changes. While some neurological symptoms may respond to therapeutic intervention
      during the initial recovery period, others may persist for many years after the
      initial insult, and often have a devastating impact on quality of life for the
      TBI victim. The aim of the current study was to develop neurobehavioral testing
      parameters designed to provide a longitudinal assessment of neurofunctional
      deficits in a rodent model of penetrating ballistic-like brain injury (PBBI). We
      report here a series of experiments in which unilateral frontal PBBI was induced
      in rats, and motor/cognitive abilities were assessed using a battery of tests
      ranging from 30 min to 10 weeks post-injury. The results showed that PBBI
      produced consistent and significant (1) neurological deficits (neuroscore
      examination: 30 min to 10 weeks post-PBBI), (2) sensorimotor dysfunction in the
      contralateral forelimb (forelimb asymmetry task: 7 and 21 days), (3) motor
      dysfunction (balance beam task: 3-7 days; and fixed-speed rotarod task: 3-28
      days), and (4) spatial learning deficits in the Morris water maze (MWM) task out
      to 10 weeks post-injury. Overall, the results of this study demonstrate that PBBI
      produces enduring motor and cognitive deficits, and identifies the optimal task
      and testing parameters for facilitating longitudinal screening of promising
      therapeutic interventions in this brain injury model.

PMID- 20684677
TI  - Brain temperature profiles during epidural cooling with the ChillerPad in a
      monkey model of traumatic brain injury.
AB  - Therapeutic hypothermia remains a promising treatment for patients with severe
      traumatic brain injury (TBI). Multiple animal studies have suggested that
      hypothermia is neuroprotective after TBI, but clinical trials have been
      inconclusive. Systemic hypothermia, the method used in almost all major clinical
      trials, is limited by the time to target temperature, the depth of hypothermia,
      and complications, problems that may be solved by selective brain cooling. We
      evaluated the effects on brain temperature of a cooling device called the
      ChillerPad,TM which is applied to the dura in a non-human primate TBI model using
      controlled cortical impact (CCI). The cortical surface was rapidly cooled to
      approximately 15 degrees C and maintained at that level for 24 h, followed by
      rewarming over about 10 h. Brain temperatures fell to 34-35 degrees C at a depth
      of 15 mm at the cortical gray/white matter interface, and to 28-32 degrees C at
      10 mm deep. Intracranial pressure was mildly elevated (8-12 mm Hg) after cooling
      and rewarming, likely due to TBI. Other physiological variables were unchanged.
      Cooling was rapidly diminished at points distant from the cooling pad. The
      ChillerPad may be useful for highly localized cooling of the brain in
      circumstances in which a craniotomy is clinically indicated. However, because of
      the delay required by the craniotomy, other methods that are more readily
      available for inducing hypothermia may be used as a bridge between the time of
      injury to placement of the ChillerPad.

PMID- 20684678
TI  - A 53-year-old woman with rapidly progressive altered mental status and ataxia.

PMID- 20684680
TI  - Alternative epidemic of different types of influenza in 2009-2010 influenza
      season, China.

PMID- 20684681
TI  - The risk of ventricular-assist device infections differs by device type.

PMID- 20684683
TI  - The urgent need for recommendations on revaccination of HIV-infected children
      after successful antiretroviral therapy.

PMID- 20684687
TI  - Rotavirus in Africa: shifting the focus to disease prevention.

PMID- 20684688
TI  - VP6: A candidate rotavirus vaccine.
AB  - Several nonliving rotavirus vaccine candidates have been evaluated in animal
      models. Among them is the VP6 protein that comprises the intermediate layer of
      the rotavirus particle. This protein was expressed as a chimera with maltose
      binding protein (MBP::VP6) and was administered intranasally to mice. When later
      challenged with rotavirus, vaccinated mice were nearly 100% protected from fecal
      shedding of rotavirus, a result strictly dependent on coadministration of an
      effective adjuvant. Protection was stimulated by only 1 dose of MBP::VP6,
      remained fully intact for at least 1 year, was effective in all strains of mice
      tested, and could also be effectively delivered orally or intrarectally. When VP6
      was derived from a human rotavirus, it stimulated protection comparable to that
      found when derived from the challenge murine EDIM strain. In contrast to live
      rotavirus vaccines, CD4(+) T cells were found to be the only lymphocytes required
      for protection. If VP6 elicits comparable protection in humans, it would
      represent a potential second-generation vaccine candidate.

PMID- 20684689
TI  - The cost-effectiveness of rotavirus vaccination in Malawi.
AB  - BACKGROUND: Rotarix (GlaxoSmithKline), a newly licensed rotavirus vaccine
      requiring 2 doses, may have the potential to save hundreds of thousands of lives
      in Africa. Nations such as Malawi, where Rotarix is currently under phase III
      investigation, may nevertheless face difficult economic choices in considering
      vaccine adoption. METHODS: The cost-effectiveness of implementing a Rotarix
      vaccine program in Malawi was estimated using published estimates of rotavirus
      burden, vaccine efficacy, and health care utilization and costs. RESULTS: With
      49.5% vaccine efficacy, a Rotarix program could avert 2582 deaths annually. With
      GAVI Alliance cofinancing, adoption of Rotarix would be associated with a cost of
      $5.07 per disability-adjusted life-year averted. With market pricing, Rotarix
      would be associated with a base case cost of $74.73 per disability-adjusted life
      year averted. Key variables influencing results were vaccine efficacy, under-2
      rotavirus mortality, and program cost of administering each dose. CONCLUSIONS:
      Adopting Rotarix would likely be highly cost-effective for Malawi, particularly
      with GAVI support. This finding holds true across uncertainty ranges for key
      variables, including efficacy, for which data are becoming available.

PMID- 20684690
TI  - The economic burden of diarrheal disease in a tertiary level hospital, Gauteng,
      South Africa.
AB  - BACKGROUND: Diarrheal disease remains one of the major causes of morbidity and
      mortality in young children in South Africa. Although a rotavirus vaccine will
      reduce rotavirus diarrheal morbidity and mortality, its introduction and
      sustainability will incur considerable costs. The aim of this study was to
      estimate the costs associated with diarrheal disease of all etiologies in
      children <5 years of age at Dr George Mukhari Hospital, a tertiary level hospital
      in Gauteng, South Africa. METHODS: Cost data were obtained by a review of
      systematically selected records of patients admitted for diarrhea during 2004 and
      the prospective recording of the treatment of consecutive inpatients admitted for
      diarrhea from February through June 2005. Data on hospital stay, medications,
      nondrug orders, and diagnostic tests were abstracted using standardized recording
      forms. Costs were calculated using 2004 and 2005 prices. Carers were interviewed
      using a standard interview schedule to determine out-of-pocket expenses. Stool
      samples were tested for rotavirus by the Medical Research Council Diarrheal
      Pathogens Unit. RESULTS: The review sample comprised 86 (20 rotavirus positive)
      patient records. The prospective sample comprised 77 inpatients (25 rotavirus
      positive). The mean duration (+/- standard deviation [SD]) of hospital stay was
      4.6 +/- 3.4 days and 5.7 +/- 4.7 days for the review and prospective samples,
      respectively. The mean total inpatient cost (+/-SD) was R5963 +/- R4070 (review
      sample) and R7256 +/- R5599 (prospective sample; P > .05). Although mean total
      costs did not differ significantly between rotavirus-negative and -positive
      samples, mean facility and antibiotic costs were significantly higher for the
      rotavirus-negative sample (P < .05) in the prospective sample. Mean out-of-pocket
      expenses (+/-SD) were R100.00 +/- R112 for inpatients. CONCLUSION: Although total
      inpatient costs did not differ significantly between the rotavirus-negative and 
      positive patients, costs for the rotavirus-negative patients tended to be higher.
      Although a rotavirus vaccine will reduce the burden of diarrheal disease, it is
      imperative that measures for reducing the incidence and severity of diarrheal
      disease due to other pathogens are strengthened.

PMID- 20684691
TI  - The epidemiology of rotavirus diarrhea in countries in the Eastern Mediterranean
      Region.
AB  - OBJECTIVE: Rotavirus is the leading cause of severe diarrhea among children
      worldwide, killing approximately 600,000 children annually, including 64,800 in
      the Eastern Mediterranean Region. Safe, effective rotavirus vaccines will be
      available soon, and accurate disease burden data will be needed to assess the
      burden of rotavirus and the value of new vaccines and monitor vaccine program
      impact. METHODS: To identify epidemiologic studies in which rotavirus diagnostics
      were applied to children with acute gastroenteritis, we performed a systematic
      literature review. We selected studies that met 4 criteria and extracted
      rotavirus data on prevalence estimates, strain identification, age distribution
      of patients, and seasonal trends. RESULTS: Of the 63 published studies with some
      rotavirus detection data, 29 met inclusion criteria. Among patients with
      diarrhea, rotavirus was detected in 40% of inpatients and 23% of outpatients. By
      3 years of age, 75% of children experienced a documented rotavirus infection.
      Circulation of rotavirus occurred year-round, and no clear relationship between
      the timing of the rotavirus peak with either season or latitude was observed.
      Comparison of country-specific rotavirus detection rates indicated that the
      proportion of hospitalizations for rotavirus infection increased with income.
      CONCLUSION: This systematic review of studies of rotavirus diarrhea among
      children in the countries of the Eastern Mediterranean Region documents that
      rotavirus is one of the most significant causes of childhood diarrhea in the
      region. The findings of this review will be used to establish sentinel hospital
      surveillance in these countries, estimate disease burden, and characterize its
      epidemiology using common protocols and diagnostics.

PMID- 20684692
TI  - Hospital health care cost of diarrheal disease in Northern Ghana.
AB  - Diarrhea caused by rotaviruses is one of the most frequent causes of
      hospitalization among pediatric patients in rural communities of developing
      countries in sub-Saharan Africa and Southeast Asia, and it is a major cause of
      death in these communities. The complexity of diarrhea and the increasing cost of
      treatment puts additional burden on the health sector. To demonstrate the
      economic burden of diarrhea to policy makers, this study was conducted to
      estimate the treatment cost of diarrhea in children <5 years old in Ghana using
      the World Health Organization protocol for cost data collection and estimation.
      The study was undertaken in Navrongo War Memorial Hospital in northern Ghana.
      Cost estimates were made for 3 treatment scenarios observed: (1) treatment by
      rehydration, (2) treatment by rehydration and antibiotics, and (3) treatment of
      diarrhea and other diseases. The average outpatient treatment costs for the 3
      treatment scenarios were US$3.86, $4.10, and $4.35 respectively, and the average
      treatment costs for hospitalization (inpatient care) were $65.14, $97.40, and
      $133.86 respectively. The annual national treatment costs, based on the 3
      treatment scenarios, ranged from $907,116 to $1,851,280 for outpatients clinic
      visits and from $701,833 to $4,581,213 for hospitalizations. The average length
      of stay for the inpatients ranged from 2.3 to 4.9 days. The study did not cover
      patient costs (ie, household costs).

PMID- 20684693
TI  - Prospective hospital-based surveillance to estimate rotavirus disease burden in
      the Gauteng and North West Province of South Africa during 2003-2005.
AB  - BACKGROUND: Rotavirus is considered to be the most common cause of serious acute
      dehydrating diarrhea worldwide. However, there is a scarcity of information on
      rotavirus disease burden in sub-Saharan Africa. METHODS: We conducted
      prospective, hospital-based surveillance for rotavirus diarrhea among children <5
      years of age at the tertiary care Dr. George Mukhari Hospital (DGM) and at the
      Brits district Hospital (BH) in the Gauteng and North West Provinces in South
      Africa; we estimated that up to 80% of children <5 years of age in their
      catchment areas who are hospitalized for diarrhea are admitted to one of these
      hospitals. RESULTS: At DGM, 2553 children <5 years of age were admitted for
      diarrhea from January 2003 through December 2005, and 852 children <5 years of
      age were treated for diarrhea at BH during 2004-2005. We examined stool specimens
      from 450 children (53%) at BH and from 1870 children (73%) admitted to DGM. An
      estimated 22.8% (95% confidence interval [CI], 21.2%-24.5%) of the children
      hospitalized with diarrhea at DGM were rotavirus positive, and the corresponding
      figure at BH was 18.2% (95% CI, 14.9%-22.1%). Among children <5 years of age
      admitted to DGM for any reason, an estimated 5.5% (95% CI, 5.1%-6.0%) had
      rotavirus diarrhea. Our incidence estimates suggest that 1 in 43-62 children in
      the area is likely to be hospitalized with rotavirus diarrhea by 2 years of age.
      CONCLUSIONS: Prevention of serious rotavirus illness by vaccination will
      substantially reduce not only the disease burden among young children but also
      the case load in South African health care facilities.

PMID- 20684694
TI  - Characterization and molecular epidemiology of rotavirus strains recovered in
      Northern Pretoria, South Africa during 2003-2006.
AB  - Rotavirus infection is the most common cause of severe dehydrating
      gastroenteritis in infants and young children and remains a significant clinical
      problem worldwide. The severity and the burden of rotavirus disease could be
      reduced through the implementation of an effective vaccine. The aim of this study
      was to characterize rotavirus strains circulating in the local community as part
      of an ongoing hospital burden of disease study when a G1P[8] rotavirus vaccine
      candidate was being evaluated in the same community. From 2003 through 2006, 729
      rotavirus-positive stool specimens were collected from children <5 years of age
      who were treated for diarrhea at Dr George Mukhari Hospital, Ga-Rankuwa, South
      Africa. Molecular characterization of the strains was performed by polyacrylamide
      gel electrophoresis and genotyping of the VP4 and VP7 alleles using well
      established seminested multiplex reverse-transcription polymerase chain reaction
      methods. In 2003, 62% of strains exhibited the short rotavirus electropherotype,
      and the most common rotavirus strain was G2P[4]. In subsequent years, predominant
      rotavirus strains included G1P[8] and G1P[6] in 2004, G3P[8] and G3P[6] in 2005,
      and G1P[8] in 2006. For the 4 years of the study, rotavirus strains with P[6]
      genotype were detected in 25% of all rotavirus-positive specimens. In addition,
      unusual G12P[6] and G8 strains were detected at a low frequency. These results
      reflect the diversity of rotavirus strains circulating in South African
      communities.

PMID- 20684695
TI  - Prevalence and diversity of rotavirus strains in children with acute diarrhea
      from rural communities in the Limpopo Province, South Africa, from 1998 to 2000.
AB  - BACKGROUND: Data regarding the prevalence and molecular epidemiology of rotavirus
      infection in rural areas of Africa are limited. In this study the prevalence and
      genetic diversity of rotaviruses in a rural South African setting were
      investigated. METHODS: During June 1998 to June 2000, 420 stool specimens were
      collected from children with acute diarrhea who visited primary health care
      clinics in the rural Vhembe region, Limpopo Province, South Africa. Group A
      rotaviruses were detected by enzyme-linked immunosorbent assay, and the G and P
      types were determined by reverse-transcription polymerase chain reaction.
      RESULTS: Of the 420 specimens, 111 (26.4%) were positive for group A rotavirus;
      P[6]G1 strains predominated (32.4%), followed by P[8]G1 (13.5%), P[6]G9 (4.5%),
      P[4]G8 (3.6%), P[4]G1 (3.6%), P[6]G8 (3.6%), and P[6]G2 (2.7%). Dual infections,
      with >1 P type, were seen in 33 (37.1%) of the positive specimens. CONCLUSION:
      The unusual serotype and genotype combinations of rotavirus circulating in the
      rural communities of the Limpopo Province highlight the need for more studies to
      monitor the geographic distribution of rotavirus strains in rural African
      settings.

PMID- 20684696
TI  - Retrospective surveillance of intussusception in South Africa, 1998-2003.
AB  - BACKGROUND: Intussusception is a common gastrointestinal emergency in children
      and appears to have a somewhat different clinical spectrum in developing
      countries. Its etiology is still unclear, but a link to infective agents and
      viruses has been highlighted. This study aimed to assess the clinical spectrum
      and prevalence of intussusception in children from the diverse South African
      population. METHODS: Retrospective data were obtained from 9 participating
      pediatric referral units on the occurrence of intussusception in South African
      children (<14 years old) during a 6-year period (1998-2003). Results were
      correlated with national population statistics. Intussusception was anatomically
      classified into ileoileal, ileocolic, and colocolic types. The clinical features,
      management, outcome, and possible causes were examined. RESULTS: We reviewed the
      occurrence and clinical spectrum of intussusception in 423 children (age, 0-14
      years) presenting with acute intussusception to 9 pediatric surgical centers. The
      mean duration of symptoms was 1.5 days, but a delayed presentation was common
      (median delay, 2.3 days). Intussusception occurred throughout the year, with a
      peak in the summer months. The majority of patients (89%) were <2 years old, and
      78% presented at age 3-18 months of age. Crude population estimates indicate an
      occurrence of 1 case per 3123 population <2 years old. Only 11% of patients
      presented after 2 years of age, and the age at presentation was significantly
      lower (P < .05) in black African patients. All ethnic groups were affected. In
      84% of patients, intussusception occurred at the ileocolic region junction, in 7%
      it was ileoileal, and in 9% it was colocolic. Colocolic intussusception appeared
      more common in black African patients, and associated pathologic conditions
      (polyps and Burkitt's lymphoma) occurred mainly in older children. Surgical
      intervention was required in 81% of patients and involved resection of gangrenous
      bowel in 40%. CONCLUSION: Intussusception appears to be a relatively frequent
      occurrence in children in South Africa. Although the clinical spectrum appears to
      vary, there is an apparent link to intestinal infection, which requires further
      investigation. A collaborative approach is required to ascertain the relationship
      of intussusception to preventable infections and to improve its diagnosis and
      management.

PMID- 20684697
TI  - Characterization of rotavirus strains detected in Windhoek, Namibia during 1998
      1999.
AB  - BACKGROUND: Namibia, located on the southwestern coast of southern Africa, is
      characterized by vast deserts, limited fresh water, and low population density.
      Mortality estimates among children <5 of age are 63 deaths per 1000 live-births,
      with diarrheal diseases contributing to 3% of these deaths. Data on the burden of
      rotavirus disease and circulating serotypes in Namibia are currently not
      available. MATERIALS AND METHODS: From May 1998 through December 1999, 815 stool
      specimens were collected from children <5 years of age who attended the Windhoek
      State Hospital, Windhoek, Namibia, for diarrhea. Specimens were screened for the
      presence of rotavirus antigens. Rotavirus-positive specimens were further
      analyzed to determine electropherotype, subgroup (SG) specificity, and G and P
      genotypes. RESULTS: Rotavirus was detected in 113 (13.8%) of 815 specimens, with
      the majority of infections occurring in children <18 months of age. Strains
      bearing 1 long electropherotype, SGII, and G1P[8] or G1P[6] specificity
      predominated during the 20-month study period. In addition to the typical winter
      rotavirus season, a peak in rotavirus infection was also observed during the
      summer. CONCLUSIONS: Serotypes G1P[8], G1P[6], G1P[4], and G2P[4] were found
      throughout the study period, predominantly in children <18 months of age. The
      observed summer rotavirus peak coincided with increased rainfall in Namibia and
      an increase in the diversity of detected serotypes. During the October to
      December 1999 peak, 2 G9P[6] strains and 1 G8P[4] strain were identified.
      Expanded and updated information on prevalence of rotavirus infection,
      circulating serotypes, and burden of disease will be required to enable local
      government to make decisions on the implementation of rotavirus vaccination in
      Namibia.

PMID- 20684698
TI  - Epidemiology of rotavirus infection in children in Blantyre, Malawi, 1997-2007.
AB  - Acute gastroenteritis caused by rotavirus infection is an important cause of
      morbidity and mortality among infants and young children in Africa. From 1997
      through 2007, we enrolled 3740 children <5 years of age with acute
      gastroenteritis who received hospital care at the Queen Elizabeth Central
      Hospital in Blantyre, Malawi. Group A rotavirus was detected in fecal specimens
      by enzyme immunoassay. Rotavirus strains were characterized for VP7 (G) and VP4
      (P) types with use of reverse-transcription polymerase chain reaction. Overall,
      rotavirus was detected in one-third of children. The median age of children with
      rotavirus gastroenteritis was 7.8 months, compared with 10.9 months for those
      without rotavirus in stool specimens (P > .001). Rotavirus circulated throughout
      the year, with the detection proportion greatest during the dry season (from May
      through October). A total of 15 single rotavirus strain types were detected
      during the study period, with genotypes P[8]G1, P[6]G8, P[4]G8, P[6]G1, P[8]G3,
      and P[6]G9 comprising 83% of all strains characterized. Serotype G12 was detected
      for the first time in Blantyre during the final 2 years of study. Zoonotic
      transmission and viral reassortment contributed to the rich diversity of strains
      identified. Current rotavirus vaccines have the potential to greatly reduce the
      rotavirus disease burden in Malawi, but they will be required to protect against
      a broad range of rotavirus serotypes in a young population with year-round
      rotavirus exposure.

PMID- 20684699
TI  - Molecular characterization of rotavirus strains circulating among children with
      acute gastroenteritis in Madagascar during 2004-2005.
AB  - A survey was undertaken of the etiology of acute gastroenteritis in children <16
      years of age in Antananarivo, Madagascar, from May 2004 through May 2005. With
      use of electron microscopy of fecal specimens, 104 (36%) of 285 children were
      found to be infected with rotavirus. Rotavirus strain characterization was
      undertaken using enzyme-linked immunosorbent assay, electropherotyping, reverse
      transcription polymerase chain reaction genotyping, and nucleotide sequencing.
      The predominant group A rotavirus strain types identified were P[4]G2 (62%) and
      P[8]G9 (23%). Nucleotide sequence analysis of the VP7 genes of selected Malagasy
      G2 and G9 strains demonstrated similarity with those of other recently identified
      African rotavirus strains belonging to the same genotype.

PMID- 20684700
TI  - Rotavirus genetic diversity, disease association, and temporal change in
      hospitalized rural Kenyan children.
AB  - BACKGROUND: The effectiveness of rotavirus vaccines will be dependent on the
      immunity conferred against prevalent and emergent variants causing severe
      diarrheal disease. Longitudinal surveillance of disease-causing strains is a
      prerequisite to intervention. METHODS: Molecular characterization was conducted
      on rotavirus-positive stool samples from children admitted with diarrhea to a
      rural district hospital during 2002-2004. Extracted viral RNA was separated by
      polyacrylamide gel electrophoresis, and rotavirus VP4 (P types) and VP7 (G types)
      specificities were determined. RESULTS: Among 558 investigated cases, the
      predominant genotype was P[8]G1 (42%), followed by P[8]G9 (15%), P[4]G8 (7%),
      P[6]G8 (6%), and P[8]G8 (4%), with 10% mixed strains. Overall, there were 6
      different P types and 7 G types. No association was identified between genotype
      and child age, sex, or severity of diarrhea. The P and G genotypes and
      polyacrylamide gel electropherotypes showed significant temporal variation in
      frequency: P[8]G1 decreased from 51% (95% confidence interval [CI], 43%-58%) in
      2002 to 30% (95% CI, 24%-37%) in 2004, and P[4]G8 increased from 2% (95% CI, 0%
      5%) in 2002 to 13% (95% CI, 9%-19%). Quarterly data revealed seasonally endemic
      and emergence and/or decay patterns. CONCLUSIONS: Our study of rotavirus strains
      causing severe diarrhea in rural Kenyan children showed a predominance of P[8]G1
      and confirms the importance of G8 and G9 strains in sub-Saharan Africa.
      Considerable genetic diversity of rotavirus strains was observed, including
      substantial mixed and unusual types, coupled with significant temporal strain
      variation and emergence. These results warn of variable vaccine efficacy and the
      need for long-term surveillance of circulating rotavirus genotypes.

PMID- 20684701
TI  - Characterization of human rotavirus strains from children with diarrhea in
      Nairobi and Kisumu, Kenya, between 2000 and 2002.
AB  - Rotavirus infection is a major cause of diarrheal illness and hospitalization in
      children <5 years old in Kenya and has been described in various settings and
      locations across the country and for different time points. In this study, we
      expand on the molecular characterization of rotavirus strains collected in
      Nairobi and Kisumu, Kenya, between 2000 and 2002. Rotavirus strains were typed by
      reverse-transcription polymerase chain reaction and characterized using VP6
      monoclonal antibodies and RNA electrophoresis of the viral genome. A large
      proportion of specimens could not be genotyped; 41% did not produce a G type
      result, and 43% did not produce a P type result. Of the strains that could be
      genotyped, G1P[8] strains were predominant, followed by G2P[4] strains. In
      addition, G8 and G9 strains were seen in similar proportions Interestingly, the G
      and P combinations were more diverse among G8 and G9 rotavirus strains,
      suggesting the recent introduction of these strains into the human population.
      These observations are a link between the occasional observation of G8 and G9
      strains at the turn of the century and the high predominance of G9P[8] strains
      observed in Kenya in 2005.

PMID- 20684702
TI  - Characterization of human rotavirus recovered from children with acute diarrhea
      in Kinshasa, Democratic Republic Of Congo.
AB  - Between July and October of 2003, 2004, and 2005, outbreaks of acute
      gastroenteritis occurred among children <5 years of age in Kinshasa, Democratic
      Republic of the Congo. Stool specimens (67 in 2003, 108 in 2004, and 116 in 2005)
      were collected and screened for rotaviruses using either latex agglutination
      (Diarlex LAA; Orion Diagnostics) or enzyme immunoassay (IDEIA; DakoCytomation).
      The molecular characteristics of the rotavirus strains were then determined.
      Group A rotavirus was detected in 195 (76%) of 258 stool specimens.
      Polyacrylamide gel electrophoresis was used to observe the 11 rotavirus double
      stranded RNA segments in 83% of the 195 rotavirus-positive specimens. Six
      rotavirus group A electropherotypic patterns were noted, predominantly within the
      short classic pattern (111 [69%]) and the long pattern (37 [23%]). Mixed patterns
      were noted in the 14 remaining specimens (9%). Of the 29 samples subjected to
      subgrouping VP6 enzyme immunoassay, subgroup I predominated. Some of the
      specimens collected in 2003 (n = 26), 2004 (n = 38), and 2005 (n = 52) were
      analyzed by reverse-transcription polymerase chain reaction, which showed that t
      G8P[6] and G8P[8] strains predominated in 2003, and G1P[6] strains with short
      electropherotypic patterns predominated in 2004 and 2005. The emergence in
      Kinshasa of G8 serotypes, unusually associated with the P[6] genotype, as well as
      uncommon G1 rotavirus strains showing a short RNA pattern, is significant in
      relation to the introduction of a rotavirus vaccine and underscores the need for
      continued rotavirus serotype surveillance in the Democratic Republic of the
      Congo.

PMID- 20684703
TI  - Diversity of rotavirus VP7 and VP4 genotypes in Northwestern Nigeria.
AB  - BACKGROUND: Nigeria has recently been ranked third among the 10 countries with
      the greatest number of rotavirus disease-associated deaths per year. Estimates
      attribute up to 33,000 deaths annually to rotavirus disease in Nigerian children
      <5 years old. Although the introduction of the new oral, live attenuated
      rotavirus vaccines may not occur for another 4-6 years in developing countries,
      background data on burden of disease, cost of rotavirus disease, and
      characterization of circulating strains is required to hasten this introduction
      to children who would clearly benefit from the intervention. METHODS: Between
      July 2002 and July 2004, fecal specimens were collected from 869 infants and
      young children <5 years of age presenting with diarrhea in Kaduna, Kebbi, Sokoto,
      and Zamfara states in northwestern Nigeria. In addition, 194 control specimens
      were also collected from children matched for age. Specimens were screened for
      the presence of rotavirus antigens. Rotavirus-positive specimens were further
      analyzed to determine electropherotype, subgroup specificity, and G and P
      genotypes. RESULTS: Rotavirus was detected in 18% of children with diarrhea and
      7.2% of the age-matched case control subjects. The highest rotavirus burden was
      detected in children aged <6 months. The majority of the rotavirus-positive
      specimens revealed viruses of long electropherotypes, subgroup II specificity,
      and G1P[8] genotypes. Furthermore, more than a quarter of specimens (37%)
      displayed mixed G and P genotypes, and almost a third could not be genotyped.
      CONCLUSIONS: The high numbers of mixed rotavirus infections highlight the
      multitude of enteric pathogens to which children in African countries are
      exposed. Data on circulating rotavirus strains serve to inform African government
      officials to the serious health threat posed by rotavirus in their respective
      countries and to document the diversity of strains before vaccine introduction.

PMID- 20684704
TI  - Rotavirus VP4 and VP7 genotypes circulating in Cameroon: Identification of
      unusual types.
AB  - Rotavirus remains a priority candidate for vaccine development, because it is the
      major cause of viral diarrhea in children worldwide. This study characterized
      rotavirus strains in 195 stool specimens collected from children <5 years of age
      with diarrhea, in the Southwest Province and Western Province of Cameroon during
      1999-2000. The predominant G type was G1 (detected in 44.9% of specimens) and the
      most predominant P type was P[8] (in 82.7%). The most common G-P combination
      detected was G1P[8] (in 37.1% of specimens), followed by G9P[8] (in 14%).
      Rotavirus strains with unusual G-P combinations, such as G1P[4], G2P[8], G8P[8],
      G9P[4], G5P[8], and G10P[8], were also observed in significant numbers. Analysis
      of the age distribution showed that G1P[8] was found circulating in all age
      groups except in infants <6 months old. Strains G2P[4] and G3P[8] were identified
      in children >37 months and 19-24 months of age, respectively. Strain G9P[8] was
      found circulating among children >25 months of age. Unusual strains and mixed
      infections were found circulating in the different age groups, albeit at lower
      levels. The high prevalence of mixed infections and diversity of rotavirus
      strains detected in this first study based on genotyping of Cameroonian strains
      reinforce the need to continue with surveillance programs in Africa, where a high
      diversity of strains has been reported.

PMID- 20684705
TI  - Characterization of 2 human genotype G10 rotavirus strains, 3008CM and
      1784/CI/1999, isolated in Cameroon and Cote d'Ivoire during the 1999-2000
      rotavirus season.
AB  - During routine rotavirus surveillance projects in Cameroon and Cote d'Ivoire, 2
      fecal samples collected from 2 children <5 years of age who presented with
      symptoms of gastroenteritis were found to give anomalous G typing results. These
      specimens were strongly rotavirus positive by enzyme immunoassay, displayed VP6
      subgroup II specificity and long RNA electropherotypes, and were typed as
      rotavirus serotype G2 with monoclonal antibodies. In addition, the strains were
      typed as rotavirus VP7 genotype G3 and VP4 genotype P[8] by reverse-transcription
      polymerase chain reaction. Further investigation of the polymerase chain reaction
      G-typing results with a second set of primers revealed that the specimens were
      not genotype G3, and both samples were sequenced to elucidate the problem. Both
      strains were found to be genotype G10 by nucleotide sequence. Comparison of
      nucleotide and amino acid sequences and phylogenetic analysis of the African G10
      strains revealed that these strains are closely related to the human G10 strains
      that were detected during the 2001-2003 rotavirus season in Ghana. The detection
      of G10 rotavirus in Africa adds to the global distribution of this strain and
      strengthens the need to continue strain surveillance in developing countries to
      understand the extent of strain distribution and diversity.

PMID- 20684706
TI  - Molecular characterization and genotyping of human rotavirus strains in Abidjan,
      Cote d'Ivoire.
AB  - In this study, we characterized human rotavirus strains recovered from infants
      and young children with acute diarrhea in Abidjan, Cote d'Ivoire, during 2000
      2004. In total, 719 fecal specimens were collected from children aged 1-60 months
      with acute infantile gastroenteritis. Examination with a commercial enzyme-linked
      immunosorbent assay showed the presence of group A rotavirus antigen in 208
      diarrheal specimens (28.9%). Polyacrylamide gel electrophoresis of the RNA
      extracted from rotavirus-positive stools yielded a variety of "long" and "short"
      RNA electropherotypes, which were used to help select strains for VP4 and VP7
      genotyping. VP7 genotype G1 strains were circulating most commonly during the
      study period (53%), followed by G2 (22%) and G3 (5%) strains. Strains with
      multiple VP7 genotype reactivity were observed in 7.6% of specimens, and a
      similar number (8%) could not be typed at all. VP4 P[6] and P[8] strains
      circulated at similar levels (33%). Strains demonstrating multiple VP4 types were
      quite common (9%); however, 20% of the strains were untypeable by the methods
      used. Rotavirus strain diversity in Cote d'Ivoire was similar to that observed in
      other West African countries.

PMID- 20684707
TI  - Antigenic and molecular characterization of unusual rotavirus strains in Burkina
      Faso in 1999.
AB  - Thirty-six of 37 rotavirus strains recovered from the diarrheal stools of 166
      children <3 years of age in Burkina Faso were characterized at both the antigenic
      and molecular levels. The rotavirus strains were confirmed by polyacrylamide gel
      electrophoresis; 30 displayed predominantly short electropherotype patterns, and
      6 had a long RNA pattern. The strains were subgrouped by monoclonal antibody
      enzyme immunoassay for VP6 and were typed as subgroup I (29 of 30 short rotavirus
      strains) and subgroup II (5 of 6 long strains). The VP7 serotyping and genotyping
      showed that all 6 viruses with long electropherotype patterns were G1. The short
      strains were determined to be VP7 serotype G2 by reverse-transcription polymerase
      chain reaction (PCR) in 27 strains and nucleic acid sequencing of selected
      strains, although only 1 reacted with the G2-specific monoclonal antibodies.
      Finally, the short patterns were shown by the PCR genotyping method to be VP4
      genotype P[6], and the long patterns were shown to be P[8]. The predominant
      strain found in Burkina Faso in this small study was an unusual G2P[6] strain
      that showed a short RNA electropherotype and VP6 subgroup I specificity and
      failed to react with a panel of G2-specific monoclonal antibodies.

PMID- 20684708
TI  - Review of rotavirus studies in Africa: 1976-2006.
AB  - BACKGROUND: Rotavirus is a common cause of severe diarrheal disease in children
      worldwide. Ninety percent of the associated deaths occur in sub-Saharan Africa
      and South East Asia. Our aim was to review the prevalence of rotavirus infection
      in Africa over the past 30 years. METHODS: Eligible studies were identified from
      3 Medline searches. Only studies including children <5 years of age that included
      >50 children and had an observational period >3 months were included. The data
      were analyzed during 3 periods (1976-1985, 1986-1995, and 1996-2006), as a
      summary (1976-2006), and by different study settings (ie, hospital, outpatient
      department, and combined). RESULTS: The initial search identified 206 studies
      from 27 countries during 1976-2006. The refined search yielded 101 studies, of
      which 58 (57%) were hospital based, 25 (25%) were outpatient studies, and 18
      (18%) were combined. Rotavirus was detected in 25% (interquartile range, 16%-32%)
      of stool samples. Rotavirus was the most common agent identified in 73% of
      studies in which multiple diarrheal agents were determined. CONCLUSION: Rotavirus
      is an important cause of severe diarrheal disease in children <5 years of age in
      Africa. Clinical trials in South Africa and Malawi have shown that severe
      rotavirus disease is a vaccine-preventable entity in Africa.

PMID- 20684710
TI  - Rotavirus disease in Guinea-Bissau, West Africa: a review of longitudinal
      community and hospital studies.
AB  - Rotavirus is one of the most common causes of childhood diarrheal disease and
      deaths in sub-Saharan Africa. This article reviews community- and hospital-based
      surveillance of rotavirus disease in Bissau, Guinea-Bissau, West Africa. Here,
      rotavirus infections exhibit a seasonal pattern, with annual epidemics occurring
      during the relatively dry and cooler months, from January to April, and few cases
      registered from May to December. Most children (74%) experience their first
      infection before the age of 2 years, and rotavirus has been identified as the
      most pathogenic of all diarrheal agents during 2 large prospective studies
      involving several hundred children <5 years of age. In the hospital setting,
      rotavirus accounts for a high case-fatality ratio (8%) and a high rate of
      nosocomial transmission; during the rotavirus season, 23% of all children
      admitted for nonrotavirus diarrheal disease acquired rotavirus infection during
      hospitalization (>48 h after admission).

PMID- 20684711
TI  - The effect of high-dose vitamin A supplementation given with bacille Calmette
      Guerin vaccine at birth on infant rotavirus infection and diarrhea: a randomized
      prospective study from Guinea-Bissau.
AB  - BACKGROUND: Prophylactic vitamin A supplementation (VAS) reduces mortality and
      may reduce morbidity associated with diarrhea in children >6 months of age.
      Rotavirus is the most common cause of acute dehydrating diarrhea among children
      worldwide. METHODS: In a randomized placebo-controlled study of 50,000 IU of
      vitamin A versus placebo given with bacille Calmette-Guerin vaccine at birth, 287
      infants were followed up with weekly interviews and stool sample obtainment to
      test the hypothesis that VAS reduced the risk of rotavirus infection. RESULTS:
      VAS was associated with increased risk of rotavirus infection and diarrhea
      (incidence rate ratio [IRR] of infection, 1.72 [95% confidence interval (CI),
      1.04-2.85]; IRR of diarrhea, 3.74 [95% CI, 1.40-9.98]) among children <6 months
      of age. There was no effect in older children. VAS had a beneficial effect on
      nonrotavirus diarrhea in boys <6 months of age (IRR, 0.51; 95% CI, 0.27-0.95) and
      a detrimental effect in girls >6 months of age (IRR, 1.84; 95% CI, 0.96-3.55).
      CONCLUSION: VAS at birth did not reduce rotavirus morbidity. The effect of VAS on
      nonrotavirus diarrhea may differ by sex, being more beneficial in boys. Clinical
      trials registration. NCT00168597 .

PMID- 20684709
TI  - The global spread of rotavirus G10 strains: Detection in Ghanaian children
      hospitalized with diarrhea.
AB  - From October 2003 through September 2004, a total of 289 stool samples were
      collected from children <5 years of age who had severe diarrhea at admission to
      or when visiting the emergency department at the Navrongo War Memorial Hospital
      in rural Ghana during a study on rotavirus disease burden. Rotavirus antigen was
      detected in 115 stool samples (39.8%) tested for rotavirus. Four rotavirus
      positive samples were found to bear G10P[6] specificity by reverse-transcription
      polymerase chain reaction, polymerase chain reaction-enzyme-linked immunosorbent
      assay, and oligonucleotide microarray hybridization. Two of these strains further
      exhibited serotype G10 specificity by neutralization and subgroup II specificity
      by enzyme immunoassay and possessed long electropheretic patterns by
      polyacrylamide gel electrophoresis. Their VP7 genes shared a much closer
      nucleotide identity with other African human G10 strains (>97%) than with human
      G10 strain from Asia or South America (<86%) or animal strains (<85%). The VP8*
      genes of the Ghanaian G10 strains exhibited >94% identity to that of human P[6]
      virus strains and belonged to the P[6] lineage 1a. The deduced VP7 amino acid
      sequence showed that the Ghanaian strains were more closely related to human G10
      strains than to animal G10 strains. The possession of the typical human subgroup
      II specificity and the P[6] specificity (frequently found in Ghana and the rest
      of Africa) and the marked similarity in the VP7 antigenic sites suggest that
      these G10 strains may have evolved through genetic reassortment between bovine
      and human strains.

PMID- 20684712
TI  - Rotavirus strain diversity in the centre coast of Tunisia from 2000 through 2003.
AB  - An epidemiological survey investigating rotavirus infection in children was
      undertaken in the coastal region of Tunisia from January 2000 through September
      2003. A total of 309 fecal specimens were screened by enzyme-linked immunosorbent
      assay and latex agglutination assay for the presence of group A rotavirus
      antigen. The detection rate was 26.2%. Rotavirus outbreaks showed a temperature
      dependant pattern (P = .026) but no significant association with rainfall.
      Rotavirus strains isolated were analyzed by RNA polyacrylamide gel
      electrophoresis and were characterized antigenically by monoclonal antibodies to
      the VP6 subgroup. Eight RNA electropherotypes were identified, with 3 long and 5
      short different RNA profiles. Among VP6 typeable strains, all isolates with a
      long electrophoretic pattern carried the subgroup II specificity, whereas those
      with a short profile belonged to subgroup I. In total, 48 rotavirus-positive
      samples were analyzed for G and P typing by reverse-transcription polymerase
      chain reaction. A total of 8 different G and P combinations were found: G1P[8]
      (35.7%), G1P[6] (21.4%), G2P[4] (4.8%), G3P[4] (4.8%), G4P[6] (4.8%), G8P[8]
      (4.8%), G3P[8] (2.3%), and G4P[8] (2.3%). Mixed infections were detected in 19.1%
      of stool samples. The emergence in Tunisia of unconventional types, such as G8VP7
      specificity, highlights the need for a continual survey of the uncommon strains
      in North Africa.

PMID- 20684713
TI  - Molecular characterization of rotavirus strains circulating in Oman in 2005.
AB  - Limited genotyping data are available for rotavirus strains in the Middle East.
      In this study, we investigated the molecular epidemiology of human rotavirus
      strains circulating in the Sultanate of Oman during 2005. Rotavirus was detected
      in 178 (57.4%) of 310 of the diarrheal stools of young children <5 years admitted
      to hospitals and outpatients clinics. Polyacrylamide gel electrophoresis
      demonstrated the cocirculation of 8 strains, although 2 strains predominated
      across the Sultanate. Genotyping revealed the presence of human rotavirus strains
      of types G1P[8], G2P[4], and G3P[8]. Several strains exhibited unusual
      combinations of G and P genotypes and RNA electropherotypes, indicating the
      likelihood of natural reassortment events occurring with a high frequency. In
      addition, the unusual P[10] genotype was identified among the rotavirus strains,
      in combination with the G1 type.

PMID- 20684714
TI  - Rotavirus genotypes among hospitalized children in Egypt, 2000-2002.
AB  - Rotavirus type surveillance is essential to assess the success of rotavirus
      vaccines. Rotavirus strains collected in 2000-2002 during hospital-based
      surveillance for diarrhea in Egyptian children were genotyped. Of the 259 (25.2%)
      rotavirus-positive specimens, 82.4% were common strains (G1p[8], G2p[4], G4p[8]),
      and the emergent G9 type was detected in 5.3% of samples.

PMID- 20684715
TI  - Rotavirus strain types circulating in Africa: Review of studies published during
      1997-2006.
AB  - Rotavirus is responsible for more than half a million deaths among infants and
      young children worldwide each year; many of these deaths could be prevented by
      widespread use of an effective rotavirus vaccine. The diversity of rotavirus
      strains in many developing countries, where most rotavirus deaths occur, could
      represent a significant challenge to the efficacy of current vaccines. In
      anticipation of rotavirus vaccine introduction, we examined studies published
      over a 10-year period (1997-2006) from countries in Africa that examined the
      distribution of VP7 (G) and VP4 (P) rotavirus strain types in symptomatic
      children and in neonates, together with studies that undertook a more detailed
      characterization of unusual rotavirus strains. Compared with recently published
      global reviews of rotavirus strain types and a previous review of the African
      literature published before 1997, the current data indicate a substantially
      increased diversity of rotavirus strains across the continent. Notable findings
      included a reduction in the proportion of globally common serotypes; a high
      proportion of unusual P/G combinations, suggesting viral reassortment; evidence
      for zoonotic rotavirus transmission; the emergence and spread across Africa of
      serotype G9; and a high prevalence of the P[6] VP4 genotype. These data imply
      that rotavirus vaccines will need to confer protection against a wide variety of
      strain types in Africa and emphasize the importance of continued strain
      surveillance before and after the introduction of routine rotavirus vaccination.

PMID- 20684716
TI  - Genetic and antigenic diversity of human rotaviruses: potential impact on
      vaccination programs.
AB  - The successful development and implementation of rotavirus vaccines will have a
      significant impact on rotavirus-induced gastroenteritis in children worldwide.
      However, this introduction will increase the immune pressure against wild-type
      rotavirus strains circulating in the community, altering the forces and balances
      that drive rotavirus evolution. There is concern that antigenically distinct
      novel or rare strains may be selected and spread, decreasing vaccine efficacy.
      This review describes the diversity of rotavirus strains and the mechanism by
      which wild-type rotavirus strains can evolve, including genetic drift and genetic
      reassortment.

PMID- 20684717
TI  - Determination of the G and P types of previously nontypeable rotavirus strains
      from the African Rotavirus Network, 1996-2004: Identification of unusual G types.
AB  - A total of 215 nontypeable rotavirus samples collected from children <5 years of
      age by members of the African Rotavirus Network were characterized using reverse
      transcription polymerase chain reaction analysis and sequencing. The most
      predominant strain identified was P[8]G1 (46.9%). Genotypes P[8]G10, P[8]G8,
      P[6]G8, and P[7]G5 were also detected at frequencies varying from 0.5% to 2.3%.
      This study suggests that reassortment of unusual G types into a background of
      globally common genotype P[8] strains may be a major mechanism of generating
      rotavirus diversity. Nucleotide substitutions at the P[8], P[6], and G1 primer
      binding sites accounted for the failure to type these strains initially. Hence,
      these findings highlight the need for regular evaluation of rotavirus genotyping
      methods.

PMID- 20684718
TI  - Burden and epidemiology of rotavirus diarrhea in selected African countries:
      preliminary results from the African Rotavirus Surveillance Network.
AB  - Severe rotavirus diarrhea in children <5 years of age is a major public health
      problem; however, limited regional and country specific data on rotavirus disease
      burden are available from sub-Saharan Africa. In June 2006, the World Health
      Organization Regional Office for Africa initiated rotavirus surveillance in
      selected African countries. With use of standardized methodology developed by the
      World Health Organization, children <5 years of age who were hospitalized with
      severe diarrhea were enrolled, and stool specimens were collected for detection
      of rotavirus strains with use of a commercial enzyme immunoassay. Rotavirus
      strains were further characterized for G and P types with use of a reverse
      transcriptase polymerase chain reaction. From June 2006 through December 2008,
      rotavirus surveillance was established at 14 sites in 11 African countries. Of
      5461 stool samples collected from children enrolled in 8 countries with 1 or 2
      complete years of data, 2200 (40%) were positive for rotavirus. Ninety percent of
      all rotavirus hospitalizations occurred among children aged 3-12 months.
      Predominant types included G1P[8] (21%), G2P[4] (7%), and P [8] (29%); however,
      unusual types were also detected, including G8P[6] (5%), G8P[8] (1%), G12P[6]
      (1%), and G12P[6] (1%). A high percentage of mixed rotavirus infections was also
      detected. These preliminary results indicate that rotavirus is a major cause of
      severe diarrheal disease in African children.

PMID- 20684719
TI  - Emergence and characterization of serotype G9 rotavirus strains from Africa.
AB  - Serotype G9 strains have been detected sporadically and in localized outbreaks in
      various African countries, including South Africa, Botswana, Malawi, Kenya,
      Cameroon, Nigeria, Ghana, Guinea-Bissau, Libya, and Mauritius. Serotype G9
      strains were analyzed to investigate genogroup characteristics, including
      subgroup specificity, electropherotype, and P and G genotypes. In addition, the
      antigenic composition of the South African G9 strains was assessed. African G9
      strains were associated with both DS-1-like characteristics and Wa-like
      characteristics, indicating the predisposition of G9 strains to frequently
      reassort. Despite these reassortment events, serotype G9 strains appear to
      maintain antigenic character in the outer capsid protein, as evident with the
      reaction of the South African G9 strains with the G9-specific monoclonal antibody
      F45:1. Phylogenetic analysis clustered African G9 strains geographically,
      regardless of genogroup characteristics, into 1 lineage (IIId). Two groups of G9
      strains, originating in India and Japan, were identified in this lineage.
      Continuous surveillance of circulating rotavirus strains in Africa is vital to
      prepare for future vaccine implementation on a continent that clearly needs such
      preventative medicines.

PMID- 20684720
TI  - Diversity of rotavirus strains circulating in west Africa from 1996 to 2000.

PMID- 20684721
TI  - Influence of potential protective mechanisms on the development of live rotavirus
      vaccines.
AB  - Rotaviruses cause extensive morbidity and mortality worldwide, thus corroborating
      the need for a vaccine that is effective in all socioeconomic environments.
      Vaccines evaluated in clinical trials have all been live attenuated rotaviruses
      that are delivered orally to mimic the excellent protection observed after
      natural infection. The mechanisms by which these vaccine candidates or wild-type
      rotaviruses elicit protection are not fully understood. During the 1980s, several
      candidate vaccines provided little protection, particularly in developing
      countries, and were discontinued. Two, however, are in the process of being
      licensed worldwide, and several others are undergoing clinical trials.
      Development of live rotavirus vaccines has been highly influenced by views
      regarding the importance of serotype-specific neutralizing antibody. Development
      of several candidate vaccines is based on the concept that neutralizing antibody
      is the primary determinant of protection. These candidates, including 1 of the 2
      being licensed worldwide (RotaTeq), are composed of multiple rotavirus strains
      representative of the major human rotavirus serotypes. The other group of
      candidates has been developed based on the theory that protection is not solely
      dependent on neutralizing antibody. These candidates are composed of single
      rotavirus strains and include the other vaccine being licensed worldwide
      (Rotarix). Studies that provide the basis for each approach will be presented and
      discussed.

PMID- 20684722
TI  - Rotarix in developing countries: paving the way for inclusion in national
      childhood immunization programs in Africa.
AB  - Rotavirus gastroenteritis causes more than half a million deaths annually among
      children aged <5 years, the great majority of which occur in Africa and Asia.
      Vaccination is considered to be the most effective public health strategy to
      prevent rotavirus disease and to reduce the significant global burden of
      rotavirus gastroenteritis. Rotarix (GlaxoSmithKline Biologicals) is an oral, live
      attenuated rotavirus vaccine derived from a human G1P[8] rotavirus strain.
      Results of phase III studies in Europe, Latin America, and Asia have shown that
      Rotarix offers sustained high protection against severe rotavirus gastroenteritis
      during the first 2 years of life, when disease burden is highest, with broad
      protection demonstrated against each of the 5 main rotavirus types that circulate
      globally (G1, G2, G3, G4, and G9). Coupled with the availability of local burden
      of disease data and promising interim efficacy data from an ongoing study in
      Malawi and South Africa, this further reinforces the case for introduction of
      this rotavirus vaccine in national childhood immunization programs in Africa,
      where rotavirus-related mortality is significant.

PMID- 20684723
TI  - RotaTeq: Progress toward developing world access.
AB  - Phase III studies of an oral, live, pentavalent, human-bovine reassortant
      rotavirus vaccine (RotaTeq; Merck) in developed countries have demonstrated that
      it is well tolerated with regard to intussusception and other adverse events and
      is efficacious in preventing rotavirus gastroenteritis and associated healthcare
      encounters. However, it cannot be assumed that rotavirus vaccines will be equally
      efficacious in infants and young children in the developing world. Differences in
      host populations, associated health conditions, and the epidemiology of rotavirus
      disease could affect vaccine performance. Concern about the potential for
      differences in efficacy stems from studies of previous candidate rotavirus
      vaccines, including bovine and rhesus rotaviruses, which showed no or variable
      efficacy in developing regions. Given this history, the World Health Organization
      (WHO) recommended that the efficacy of "new" rotavirus vaccines should be
      demonstrated in diverse geographic areas, including developing countries, before
      widespread implementation. Successful implementation of any rotavirus vaccine in
      the developing world requires additional clinical research and sharing of early
      introduction experiences. We discuss efforts to bring RotaTeq vaccine to the
      developing world. Critical steps to achieve this goal include the clinical
      evaluation of vaccine safety and efficacy in a multisite trial in Asia and
      Africa, evaluation of concomitant use with other pediatric vaccines routinely
      used, and vaccine assessment in special populations (premature, human
      immunodeficiency virus-infected, and malnourished infants). Completion of WHO
      prequalification of RotaTeq and affordability are also key requirements to
      routine vaccine introduction. The RotaTeq Partnership with the Nicaraguan
      Ministry of Health provides an example of the successful introduction of this
      vaccine into a developing world country.

PMID- 20684724
TI  - Comparison of 2 different regimens for reactogenicity, safety, and immunogenicity
      of the live attenuated oral rotavirus vaccine RIX4414 coadministered with oral
      polio vaccine in South African infants.
AB  - BACKGROUND: A phase II, randomized, double-blind, placebo-controlled study was
      conducted in South Africa during 2003-2004 to evaluate the safety,
      reactogenicity, and immunogenicity of 2 regimens of the live attenuated oral
      human rotavirus vaccine RIX4414 when coadministered with the Expanded Program on
      Immunization childhood vaccines, including oral polio vaccine. METHODS: Healthy
      infants were randomized (2:2:1) to receive either 2 doses of RIX4414 (n = 190; at
      10 and 14 weeks, with placebo at 6 weeks), 3 doses of RIX4414 (n = 189; at 6, 10,
      and 14 weeks), or 3 doses of placebo (n = 96), all with concomitant routine
      vaccinations. The antirotavirus IgA seroconversion rate was assessed using enzyme
      linked immunosorbent assay at 2 months after the last dose of RIX4414 or placebo.
      Antipolio types 1, 2, and 3 antibodies were measured using a virus neutralization
      assay. Solicited symptoms were recorded for 15 days after each dose. RESULTS: The
      antirotavirus IgA seroconversion rates were similar in the RIX4414 2- and 3-dose
      groups (44.3% and 44.4%, respectively; P = .544, by 1-sided Fisher exact test)
      and antirotavirus IgA geometric mean concentrations were also comparable.
      Seroprotection rates for antipolio types 1, 2, and 3 antibodies were high (93%
      100%) and were not significantly different among groups. Solicited symptoms
      reported within 15 days after vaccination were similar in all groups.
      CONCLUSIONS: The immune seroconversion response to the RIX4414 vaccine with 3
      doses was not superior to the 2-dose regimen. There was no interference by either
      regimen with antibody response to oral polio vaccine, and RIX4414 was well
      tolerated when given with routine vaccinations.

PMID- 20684727
TI  - No evidence of an association between the APOBEC3B deletion polymorphism and
      susceptibility to HIV infection and AIDS in Japanese and Indian populations.

PMID- 20684729
TI  - Proteome-wide anti-hepatitis C virus (HCV) and anti-HIV antibody profiling for
      predicting and monitoring the response to HCV therapy in HIV-coinfected patients.
AB  - We quantified antibody responses to the hepatitis C virus (HCV) proteome that are
      associated with sustained virologic response (SVR) in human immunodeficiency
      virus (HIV)/HCV-coinfected patients treated with pegylated interferon and
      ribavirin. Analysis of pre- and posttreatment samples revealed significant
      decreases in the combined anti-core, anti-E1, and anti-NS4 HCV antibody titers in
      those with SVRs but not in those who experienced relapse or who did not respond.
      Furthermore, anti-HIV p24 antibody titers inversely correlated with treatment
      response. These results suggest that profiling anti-HCV antibody is useful for
      monitoring HCV therapy, especially in discriminating between those who experience
      relapse and those who have SVRs at 48 weeks.

PMID- 20684730
TI  - Screening chemicals for thyroid-disrupting activity: A critical comparison of
      mammalian and amphibian models.
AB  - In order to minimize risks to human and environmental health, chemical safety
      assessment programs are being reinforced with toxicity tests more specifically
      designed for detecting endocrine disrupters. This includes the necessity to
      detect thyroid-disrupting chemicals, which may operate through a variety of modes
      of action, and have potential to impair neurological development in humans, with
      resulting deficits of individual and social potential. Mindful of these concerns,
      the consensus favors in vivo models for both hazard characterization (testing)
      and hazard identification (screening) steps, in order to minimize false
      negatives. Owing to its obligate dependence on thyroid hormones, it has been
      proposed that amphibian metamorphosis be used as a generalized vertebrate model
      for thyroid function in screening batteries for detection of thyroid disrupters.
      However, it seems unlikely that such an assay would ever fully replace in vivo
      mammalian assays currently being validated for human health risk assessment: in
      its current form the amphibian metamorphosis screening assay would not provide
      capacity for reliably detecting other modes of endocrine-disrupting activity.
      Conversely, several candidate mammalian screening assays appear to offer robust
      capacity to detect a variety of modes of endocrine-disrupting activity, including
      thyroid activity. To assess whether omission of an amphibian metamorphosis assay
      from an in vivo screening battery would generate false negatives, the response of
      amphibian and mammalian assays to a variety known thyroid disrupters, as reported
      in peer-reviewed literature or government agency reports, was critically
      reviewed. Of the chemicals investigated from the literature selected (41), more
      had been tested in mammalian studies with thyroid-relevant endpoints (32) than in
      amphibian assays with appropriate windows of exposure and developmental endpoints
      (27). One chemical (methoxychlor) was reported to exhibit thyroid activity in an
      appropriate amphibian assay in the absence of corresponding activity in a
      suitable mammalian assay, whereas none of the chemicals surveyed were reported as
      thyroid active in mammalian assays but reported as negative in an appropriate
      amphibian assay. Given the need for one or more in vivo mammalian assays for
      screening chemicals for detecting (anti-)estrogenic/(anti-)androgenic activity
      and effects on steroidogenesis, inclusion of an in vivo amphibian assay
      specifically to detect thyroid disrupters would likely be as an addition to these
      mammalian assays. As there is little convincing evidence that an amphibian
      screening assay would detect significant numbers of thyroid-active chemicals not
      picked up by mammalian assays, the routine use of an amphibian metamorphosis
      assay at screening level could introduce unnecessary and unjustified redundancy
      into chemical safety assessment programs, when there is pressure to reduce animal
      use in toxicity testing.

PMID- 20684731
TI  - Design of a pectin-based microparticle formulation using zinc ions as the cross
      linking agent and glutaraldehyde as the hardening agent for colonic-specific
      delivery of resveratrol: in vitro and in vivo evaluations.
AB  - The aim of this study was to develop a colon-specific microparticle formulation
      based on pectin. Resveratrol was used as a model drug due to its potential
      therapeutic efficacy on colitis and colon cancer. Microparticles were produced by
      cross-linking pectin molecules with zinc ions and with glutaraldehyde as
      hardening agent for pectins. Different microparticles were prepared by varying
      the formulation variables. Effect of these formulation variables were
      investigated on particle shape and size, moisture content and weight-loss during
      drying, encapsulation efficiency, swelling-erosion ratio, and drug release
      pattern of the formulated microparticles. Formulation conditions were optimized
      based on the in vitro drug release study. Morphology, Fourier transform infrared
      spectroscopy, stability, and in vivo pharmacokinetic study of the microparticles
      prepared at the optimized formulation conditions were performed. Microparticles
      were spherical with <1 mm diameter and encapsulation efficiencies of >94%. The
      glutaraldehyde-modified microparticles prepared at optimized formulation
      conditions revealed colon specific in vitro and in vivo drug release. Plasma
      appearance of drug was delayed for 4-5 h after their administration directly into
      stomach, but displayed comparable area under the curve to other controls in the
      experiment, indicating the potential of the developed formulation as a colon
      specific drug delivery system.

PMID- 20684732
TI  - Factors associated with furry pet ownership among patients with asthma.
AB  - BACKGROUND: Exposure to indoor allergens is an established risk factor for poor
      asthma control. Current guidelines recommend removing pets from the home of
      patients with asthma. OBJECTIVES: This cross-sectional study was conducted to
      determine the prevalence of furry pet ownership in asthmatics compared to non
      asthmatics and to identify factors associated with furry pet ownership among
      those with asthma. Secondary analysis assessed characteristics among asthmatics
      that might be associated with allowing a furry pet into the bedroom. METHODS:
      Using data from The National Asthma Survey collected from 2003 to 2004, we
      carried out univariate and multiple regression analyses, in 2009, to identify
      independent predictors of furry pet ownership in asthma sufferers after
      controlling for potential confounders. RESULTS: Overall, asthmatics were more
      likely to own a furry pet than nonasthmatic individuals in the general population
      (49.9% versus 44.8%, p < .001). Multivariate analysis showed that female sex,
      older age, white race, and high income were independent predictors of furry pet
      ownership among asthmatics. Additionally, 68.7% of patients with asthma who own a
      furry pet allowed them into their bedroom. Higher income and carrying out < or =2
      environmental control practices in the home were associated with increased
      likelihood of allowing a furry pet into the bedroom. CONCLUSIONS: Furry pet
      ownership is equally or more common among asthmatics compared to those without
      asthma. The majority of asthmatics with furry pets allow them into the bedroom.
      Recognizing and addressing these problems may help decrease asthma morbidity.

PMID- 20684733
TI  - Overcoming heterogeneity in pediatric asthma: tobacco smoke and asthma
      characteristics within phenotypic clusters in an African American cohort.
AB  - OBJECTIVE: Asthma in children and adolescents is a heterogeneous syndrome
      comprised of multiple subgroups with variable disease expression and response to
      environmental exposures. The goal of this study was to define homogeneous
      phenotypic clusters within a cohort of children and adolescents with asthma and
      to determine overall and within-cluster associations between environmental
      tobacco smoke (ETS) exposure and asthma characteristics. METHODS: A combined
      hierarchical/k-means cluster analysis of principal component variables was used
      to define phenotypic clusters within a cohort of 6- to 20-year-old urban and
      largely minority subjects. RESULTS: Among the 154 subjects, phenotypic cluster
      analysis defined three independent clusters (Cluster 1 [n = 57]; Cluster 2 [n =
      33]; Cluster 3 [n = 58]). A small fourth cluster (n = 6) was excluded. Patients
      in Cluster 1 were predominantly males, with a relative abundance of neutrophils
      in their nasal washes. Patients in Cluster 2 were predominantly females with high
      body mass index percentiles and later-onset asthma. Patients in Cluster 3 had
      higher eosinophil counts in their nasal washes and lower Asthma Control Test
      (ACT) scores. Within-cluster regression analysis revealed several significant
      associations between ETS exposure and phenotypic characteristics that were not
      present in the overall cohort. ETS exposure was associated with a significant
      increase in nasal wash neutrophils (beta coefficient = 0.73 [95% confidence
      interval, CI: 0.11 to 1.35]; p = .023) and a significant decrease in ACT score (
      5.17 [-8.42 to -1.93]; p = .003) within Cluster 1 and a significant reduction in
      the bronchodilator-induced % change in forced expiratory volume in one second
      (FEV(1)) (-36.32 [-62.18 to -10.46]; p = .009) within Cluster 3. CONCLUSIONS:
      Clustering techniques defined more homogeneous subgroups, allowing for the
      detection of otherwise undetectable associations between environmental tobacco
      smoke exposure and asthma characteristics.

PMID- 20684734
TI  - Terra firma-forme dermatosis.
AB  - Terra firma-forme dermatosis (TFFD) is an uncommon disorder of keratinization
      with an unknown etiology in which patients present with dirt-like lesions that
      are resistant to washing. A 6-year old girl presented with the complaint of an
      asymptomatic brownish black dirt-like eruption on her body. Her parents reported
      no response to washing with soap and water. Dermatologic examination revealed
      brown hyperpigmented patches on the trunk and abdominal region. TFFD was
      suspected, and isopropyl alcohol was applied to the patient's lesions. All
      lesions completely disappeared after rubbing with alcohol. Terra firma-forme
      dermatosis is a relatively recently described entity that is much more common
      than might be expected when surveying the medical literature. With the very few
      reports found in the literature about TFFD, we believe that an increased
      awareness of this entity among primary care physicians would help decrease
      unnecessary worries or medical procedures, since TFFD lesions simply resolve by
      rubbing with isopropyl alcohol.

PMID- 20684735
TI  - Skin signs in Ehlers-Danlos syndrome: clinical tests and para-clinical methods.
AB  - OBJECTIVE: The criteria for Ehlers-Danlos syndrome (EDS) and the hypermobility
      syndrome (HMS) should be reliable. Examination for general joint hypermobility
      has high reliability but there is only sparse information on the reliability of
      skin tests, and no information on the level of normal skin extensibility. The
      present study aimed to assess skin signs by means of clinical and para-clinical
      methods. METHODS: A total of 31 EDS patients and 28 healthy controls were
      examined blinded and in random order. Inter-examiner analysis of clinical tests
      for skin extensibility, consistency, scarring, and bruising was performed,
      followed by analyses of extensibility with the suction cup (SC), consistency with
      a soft tissue stiffness meter (STSM), and thickness with ultrasonography (US).
      Semi-quantitative assessment of skin extensibility in healthy controls was
      incorporated in the tests. RESULTS: The clinical analyses demonstrated kappa
      values of: 0.72 for extensibility, 0.23 for consistency, 0.53 for scarring, and
      0.63 for bruising. Skin extensibility measurements in healthy controls (n = 28)
      were 2.79 and 2.93 cm (mean + 2 SD), respectively, by the two examiners. There
      were significant differences between patients with classical-type EDS and
      controls with respect to skin extensibility by SC (4.91 vs. 12.52 kPa/mm) and
      skin consistency by STSM (0.59 vs. 0.76 N). We found no difference in skin
      thickness. CONCLUSION: The reproducibility of the clinical skin tests was
      substantial to good, apart from the consistency measurements. We suggest that
      skin consistency is withdrawn as a diagnostic criterion. The upper level for
      normal skin extensibility should be 3 cm. SC and STSM are promising para-clinical
      methods, but their diagnostic sensitivity and specificity need to be determined.

PMID- 20684736
TI  - Elevated serum levels of MMP-2, MMP-3, and MMP-13 in Chinese patients with
      systemic lupus erythematosus.

PMID- 20684737
TI  - The role of talactoferrin alpha in the treatment of non-small cell lung cancer.
AB  - IMPORTANCE OF THE FIELD: Immunotherapeutic approaches to treating NSCLC via
      either adoptive transfer of immunity or stimulation of the endogenous immune
      system have shown increasing promise in recent years. AREAS COVERED IN THIS
      REVIEW: Talactoferrin alpha is an oral immunomodulatory agent currently in late
      stage clinical trials that acts through dendritic cell recruitment and activation
      in the gut-associated lymphoid tissue. WHAT THE READER WILL GAIN: Talactoferrin
      is a recombinant human lactoferrin that is a member of the transferrin family of
      iron-binding glycoproteins. Lactoferrins have multiple known biological
      activities including cancer protection, cellular growth and differentiation and
      antimicrobial and anti-inflammatory properties. This review discusses the
      proposed mechanism of action of talactoferrin-alpha and outlines the pre
      clinical, Phase I and II data in NSCLC. The ongoing Phase III trials are
      discussed. TAKE HOME MESSAGE: The current role of Talactoferrin alpha in the
      treatment of NSCLC is described and we explore potential future roles for this
      drug in both early stage and advanced stage disease.

PMID- 20684738
TI  - Oncolytic-adenovirus-expressed RNA interference for cancer therapy.
AB  - IMPORTANCE OF THE FIELD: RNA interference (RNAi) has generated considerable
      excitement for its potential cancer therapeutic applications. Because of the
      difficulties in delivering a large amount of siRNA to cancer cells and the short
      half-life of siRNA, it is important to choose an efficient delivery system for
      transduction of siRNA into target cells. Oncolytic adenovirus offers a better
      platform by virtue of its high transfection efficiency and selective replication
      in cancer cells. AREAS COVERED IN THIS REVIEW: This review focuses on the
      synergism between oncolytic adenovirus and siRNA antitumor responses, and
      discusses recent progresses in oncolytic-adenovirus-expressed siRNA. WHAT THE
      READER WILL GAIN: siRNA-expressing oncolytic adenovirus can generate a
      significantly enhanced antitumor effect through gene knockdown and viral
      oncolysis. TAKE HOME MESSAGE: Due to its potency and target specificity, using
      siRNA delivery by oncolytic adenovirus has generated much excitement and will
      open new avenues for treatment of human cancer.

PMID- 20684739
TI  - Enhanced dissolution rate of simvastatin using spherical crystallization
      technique.
AB  - Simvastatin is a hypocholestrolemic drug that is insoluble in water. Its low
      water solubility rate limits the pharmacological effects. The aim of this study
      was to improve the dissolution rate of simvastatin using spherical
      crystallization method. The drug was dissolved in boiling dichloromethane as the
      good solvent. This solution was added to 5 degrees C water as the non-solvent.
      After sedimentation, isopropyl acetate was added as the bridging solvent. At the
      end the crystals were collected and dried for 12 h in a 50 degrees C oven. The
      FTIR and DSC results showed no change in the drug after crystallization process.
      XRPD studies showed the sharp peaks are present in the diffractograms of
      spherical crystals with minor reduction in height of the peaks. The particle size
      of spherical aggregates was about 37 MUm and the dissolution efficiency of
      simvastatin up to 60 min increased to about 2-fold in phosphate buffer solution
      containing 0.5% sodium dodecyl sulfate (pH 7) using the rotating paddle method.
      Spherical crystals showed enhanced solubility than untreated powder possibly due
      to partial conversion to amorphous form. Their dissolution rate at 60 min was
      still 4-fold of untreated powder when stored at 25 degrees C and 84% relative
      humidity for one month.

PMID- 20684745
TI  - Atypical antipsychotics for the treatment of behavioral and psychological
      symptoms in dementia, with a particular focus on longer term outcomes and
      mortality.
AB  - IMPORTANCE OF THE FIELD: Many people with Alzheimer's disease (AD) and other
      dementias are prescribed atypical antipsychotics for behavioral and psychiatric
      symptoms such as aggression and psychosis. Recent evidence has highlighted safety
      concerns regarding antipsychotics in these individuals. AREAS COVERED IN THIS
      REVIEW: We summarize the evidence pertaining to efficacy and safety from short
      term randomized controlled trials (up to 12 weeks), key findings from case
      register studies and more detailed discussion of longer term outcome studies,
      including longer term mortality risk of antipsychotics in AD. WHAT THE READER
      WILL GAIN: The review aims to provide a balanced and up to date overview of the
      efficacy and safety concerns related to atypical antipsychotics in people with
      AD, in particular providing a detailed overview of mortality risk, and a personal
      interpretation of the implications and recommendations for the way forward. TAKE
      HOME MESSAGE: Atypical antipsychotics confer modest benefits for short-term (up
      to 12 weeks) treatment of aggression and psychosis in AD. These benefits have to
      be balanced against the risk of serious adverse events including 1.5 - 1.8-fold
      increased mortality. The benefits are less clear-cut with longer term
      prescribing, but the mortality risk remains significantly elevated.
      Pharmacogenetics may provide an opportunity to more effectively focus prescribing
      in the future.

PMID- 20684747
TI  - Protective effects of oleanolic acid on cerebral ischemic damage in vivo and
      H(2)O(2)-induced injury in vitro.
AB  - CONTEXT: Oleanolic acid (OA), a triterpenoid compound, exists in many plants. It
      has numerous bioactivities and has been used to treat hepatitis in China.
      However, few studies have reported its effect on the central nervous system,
      especially in ischemic stroke. OBJECTIVE: To explore the protective effects of OA
      on cerebral ischemic injury for the first time. MATERIALS AND METHODS: Survival
      time was tested in mice injured by bilateral common carotid artery ligation
      (BCCAL). Neurological function, infarct area, cerebral edema, superoxide
      dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) were
      estimated in rats operated by middle cerebral artery occlusion (MCAO). Cell
      survival, lactate dehydrogenase (LDH), SOD, reduced glutathione (GSH), MDA,
      mitochondrial membrane potential (MMP) and succinic dehydrogenase (SDH) were
      detected in H(2)O(2)-injured PC12 cells. RESULTS: Pre-administration with OA
      significantly prolonged survival time in mice at 50 and 25 mg/kg, alleviated
      neurological function, infarct area and cerebral edema, increased SOD and GSH-Px
      activities and decreased MDA level in rats at 25 and 12.5 mg/kg. Pre-treatment
      with OA at 10 and 1 MUM remarkably improved cell survival, enhanced SOD activity
      and GSH content, reduced LDH and MDA levels and reversed the lowering of MMP and
      SDH activity. DISCUSSION AND CONCLUSION: These results demonstrate that oleanolic
      acid effectively alleviates cerebral ischemic damage in vivo and oxidative injury
      in vitro, which may be in part due to the modulation of endogenous antioxidants
      and the improvement of mitochondrial function. Oleanolic acid may be a potential
      medicine for attenuating ischemic stroke.

PMID- 20684746
TI  - Metabolism considerations for kinase inhibitors in cancer treatment.
AB  - IMPORTANCE OF THE FIELD: A concerted effort by the pharmaceutical industry over
      the last decade has led to the successful clinical development of protein kinase
      inhibitors as effective targeted therapies for certain cancers. AREAS COVERED IN
      THIS REVIEW: This review details eight small molecule kinase inhibitors that have
      been approved for the treatment of cancer in either the US or Europe as of March
      2010: imatinib, sorafenib, gefitinib, erlotinib, dasatinib, lapatinib, sunitinib
      and nilotinib. These eight compounds vary from the relatively specific inhibitor
      lapatinib to the more promiscuous kinase inhibitors dasatinib and sunitinib. WHAT
      THE READER WILL GAIN: A brief discussion on the biology of each inhibitor,
      selectivity over other kinases and toxicity is provided. A more detailed
      discussion on the metabolism, drug transporters, drug-drug interactions and
      possible roles of metabolism in compound toxicity is provided for each compound.
      TAKE HOME MESSAGE: The majority of the currently approved kinase inhibitors is
      heavily influenced by drug transporters and significantly affected by CYP3A4
      inhibitors/inducers. At least three, gefitinib, erlotinib and dasatinib, are
      metabolized to form reactive metabolites capable of covalently-binding
      biomolecules.

PMID- 20684748
TI  - Tissue-engineered model for real-time monitoring of liver inflammation.
AB  - Tissue-engineered in vitro models have the potential to be used for investigating
      inflammation in the complex microenvironment found in vivo. We have developed an
      in vitro model of hepatic tissue that facilitates real-time monitoring of
      endothelium activation in liver tissue. This was achieved by creating a layered
      coculture model in which hepatocytes were embedded in collagen gel and a reporter
      clone of endothelial cells, which synthesizes green fluorescent protein in
      response to nuclear factor-kappa B (NF-kappaB) activation, was overlaid on top of
      the gel. The efficacy of our approach was established by monitoring in real time
      the dynamics of NF-kappaB-regulated fluorescence in response to tumor necrosis
      factor alpha. Our studies revealed that endothelial cells in coculture with
      hepatocytes exhibited a similar NF-kappaB-mediated fluorescence to both pulse and
      step stimulation of lipopolysaccharide. By contrast, endothelial cells in
      monoculture displayed enhanced NF-kappaB-regulated fluorescence to step in
      comparison to pulse lipopolysaccharide stimulation. The NF-kappaB-mediated
      fluorescence correlated with endothelial cell expression of NF-kappaB-regulated
      genes such as intercellular adhesion molecule 1, vascular cell adhesion molecule
      1, and E-Selectin, as well as with leukocyte adhesion. These findings suggest
      that our model provides a powerful platform for investigating hepatic endothelium
      activation in real time. 

PMID- 20684750
TI  - The innate immune system and diabetes mellitus: the relevance of periodontitis? A
      hypothesis.
AB  - About a decade ago, a hypothesis was proposed suggesting that the innate immune
      system, including acute-phase reactants, contribute to the development of T2DM
      [Type 2 DM (diabetes mellitus)] and the metabolic syndrome. In this model, it was
      hypothesized that the innate immune system modulates the effects of many factors,
      including genes, fetal programming, nutrition and aging, upon the later
      development of metabolic problems associated with insulin resistance. In this
      present article, we expand this hypothesis by looking at the involvement of
      periodontitis in DM and its complications. Periodontitis is a common inflammatory
      process involving the innate immune system and is associated with DM. We will
      also illustrate how dental disease is important in patients with DM and could be
      implicated in various diabetic complications.

PMID- 20684751
TI  - The taper of cast post preparation measured using innovative image processing
      technique.
AB  - BACKGROUND: No documentation in the literature about taper of cast posts. This
      study was conducted to measure the degree of cast posts taper, and to evaluate
      its suitability based on the anatomy aspects of the common candidate teeth for
      post reconstruction. METHODS: Working casts for cast posts, prepared using Gates
      Glidden drills, were collected. Impressions of post spaces were made using
      polyvinyl siloxan putty/wash technique. Digital camera with a 10' high quality
      lens was used for capturing two digital images for each impression; one in the
      Facio-Lingual (FL) and the other in the Mesio-Distal (MD) directions. Automated
      image processing program was developed to measure the degree of canal taper. Data
      were analyzed using Statistical Package for Social Sciences software and One way
      Analysis of Variance. RESULTS: Eighty four dies for cast posts were collected: 16
      for each maxillary anterior teeth subgroup, and 18 for each maxillary and
      mandibular premolar subgroup. Mean of total taper for all preparations was 10.7
      degree. There were no statistical differences among the total taper of all groups
      (P = .256) or between the MD and FL taper for each subgroup. Mean FL taper for
      the maxillary first premolars was lower significantly (P = .003) than the
      maxillary FL taper of the second premolars. FL taper was higher than the MD taper
      in all teeth except the maxillary first premolars. CONCLUSIONS: Taper produced
      did not reflect the differences among the anatomy of teeth. While this technique
      deemed satisfactory in the maxillary anterior teeth, the same could not be said
      for the maxillary first premolars. Careful attention to the root anatomy is
      mandatory.

PMID- 20684749
TI  - The vascular contribution to Alzheimer's disease.
AB  - AD (Alzheimer's disease) is a progressive neurodegenerative disease of unknown
      origin. Despite questions as to the underlying cause(s) of this disease, shared
      risk factors for both AD and atherosclerotic cardiovascular disease indicate that
      vascular mechanisms may critically contribute to the development and progression
      of both AD and atherosclerosis. An increased risk of developing AD is linked to
      the presence of the apoE4 (apolipoprotein E4) allele, which is also strongly
      associated with increased risk of developing atherosclerotic cardiovascular
      disease. Recent studies also indicate that cardiovascular risk factors, including
      elevated blood cholesterol and triacylglycerol (triglyceride), increase the
      likelihood of AD and vascular dementia. Lipids and lipoproteins in the
      circulation interact intimately with the cerebrovasculature, and may have
      important effects on its constituent brain microvascular endothelial cells and
      the adjoining astrocytes, which are components of the neurovascular unit. The
      present review will examine the potential mechanisms for understanding the
      contributions of vascular factors, including lipids, lipoproteins and
      cerebrovascular Abeta (amyloid beta), to AD, and suggest therapeutic strategies
      for the attenuation of this devastating disease process. Specifically, we will
      focus on the actions of apoE, TGRLs (triacylglycerol-rich lipoproteins) and TGRL
      lipolysis products on injury of the neurovascular unit and increases in blood
      brain barrier permeability.

PMID- 20684752
TI  - Treatment of distal humeral fractures using conventional implants. Biomechanical
      evaluation of a new implant configuration.
AB  - BACKGROUND: In the face of costly fixation hardware with varying performance for
      treatment of distal humeral fractures, a novel technique (U-Frame) is proposed
      using conventional implants in a 180 degrees plate arrangement. In this in-vitro
      study the biomechanical stability of this method was compared with the
      established technique which utilizes angular stable locking compression plates
      (LCP) in a 90 degrees configuration. METHODS: An unstable distal 3-part fracture
      (AO 13-C2.3) was created in eight pairs of human cadaveric humeri. All bone pairs
      were operated with either the "Frame" technique, where two parallel plates are
      distally interconnected, or with the LCP technique. The specimens were cyclically
      loaded in simulated flexion and extension of the arm until failure of the
      construct occurred. Motion of all fragments was tracked by means of optical
      motion capturing. Construct stiffness and cycles to failure were identified for
      all specimens. RESULTS: Compared to the LCP constructs, the "Frame" technique
      revealed significant higher construct stiffness in extension of the arm (P =
      0.01). The stiffness in flexion was not significantly different (P = 0.16).
      Number of cycles to failure was found significantly larger for the "Frame"
      technique (P = 0.01). CONCLUSIONS: In an in-vitro context the proposed method
      offers enhanced biomechanical stability and at the same time significantly
      reduces implant costs.

PMID- 20684753
TI  - No influence of the polymorphisms CYP2C19 and CYP2D6 on the efficacy of
      cyclophosphamide, thalidomide, and bortezomib in patients with Multiple Myeloma.
AB  - BACKGROUND: The response to treatment varies among patients with multiple myeloma
      and markers for prediction of treatment outcome are highly needed. Bioactivation
      of cyclophosphamide and thalidomide, and biodegradation of bortezomib, is
      dependent on cytochrome P450 metabolism. We explored the potential influence of
      different polymorphisms in the CYP enzymes on the outcome of treatment. METHODS:
      Data was analyzed from 348 patients undergoing high-dose treatment and stem cell
      support in Denmark in 1994 to 2004. Clinical information on relapse treatment in
      243 individual patients was collected. The patients were genotyped for the non
      functional alleles CYP2C19*2 and CYP2D6*3, *4, *5 (gene deletion), *6, and CYP2D6
      gene duplication. RESULTS: In patients who were treated with bortezomib and were
      carriers of one or two defective CYP2D6 alleles there was a trend towards a
      better time-to-next treatment. We found no association between the number of
      functional CYP2C19 and CYP2D6 alleles and outcome of treatment with
      cyclophosphamide or thalidomide. Neither was the number of functional CYP2C19 and
      CYP2D6 alleles associated with neurological adverse reactions to thalidomide and
      bortezomib. CONCLUSION: There was no association between functional CYP2C19 and
      CYP2D6 alleles and treatment outcome in multiple myeloma patients treated with
      cyclophosphamide, thalidomide or bortezomib. A larger number of patients treated
      with bortezomib are needed to determine the role of CYP2D6 alleles in treatment
      outcome.

PMID- 20684754
TI  - A systematic review of evidence for the added benefits to health of exposure to
      natural environments.
AB  - BACKGROUND: There is increasing interest in the potential role of the natural
      environment in human health and well-being. However, the evidence-base for
      specific and direct health or well-being benefits of activity within natural
      compared to more synthetic environments has not been systematically assessed.
      METHODS: We conducted a systematic review to collate and synthesise the findings
      of studies that compare measurements of health or well-being in natural and
      synthetic environments. Effect sizes of the differences between environments were
      calculated and meta-analysis used to synthesise data from studies measuring
      similar outcomes. RESULTS: Twenty-five studies met the review inclusion criteria.
      Most of these studies were crossover or controlled trials that investigated the
      effects of short-term exposure to each environment during a walk or run. This
      included 'natural' environments, such as public parks and green university
      campuses, and synthetic environments, such as indoor and outdoor built
      environments. The most common outcome measures were scores of different self
      reported emotions. Based on these data, a meta-analysis provided some evidence of
      a positive benefit of a walk or run in a natural environment in comparison to a
      synthetic environment. There was also some support for greater attention after
      exposure to a natural environment but not after adjusting effect sizes for
      pretest differences. Meta-analysis of data on blood pressure and cortisol
      concentrations found less evidence of a consistent difference between
      environments across studies. CONCLUSIONS: Overall, the studies are suggestive
      that natural environments may have direct and positive impacts on well-being, but
      support the need for investment in further research on this question to
      understand the general significance for public health.

PMID- 20684755
TI  - Detection and prevalence of Anaplasma phagocytophilum and Rickettsia helvetica in
      Ixodes ricinus ticks in seven study areas in Sweden.
AB  - BACKGROUND: Tick-borne Anaplasma phagocytophilum and Rickettsia spp. are
      considered to be emerging human pathogens, but only limited data are available on
      their occurrence in Sweden. Two real-time PCR assays followed by nested PCR and
      sequence analysis were carried out to investigate the prevalence of A.
      phagocytophilum and spotted fever rickettsiae in ticks from seven areas in
      Sweden. RESULTS: In 139 pooled samples, representing a total of 1245 Ixodes
      ricinus ticks (204 larvae, 963 nymphs, 38 males, 40 females), the overall
      positive mean infection prevalence was 1.3-15.0% for A. phagocytophilum and 1.5
      17.3% for R. helvetica. A. phagocytophilum was only detected in nymphs (1.7
      19.4%), whereas R. helvetica was detected in all three tick stages. Support for
      vertical and transstadial transmission was only obtained for R. helvetica. Both
      agents showed similar infection rates across study areas, although infection
      rates were greater in coastal areas. CONCLUSIONS: The results show that both
      pathogens occurred in all seven locations, indicating that they are prevalent in
      Sweden and should be considered etiological agents in patients recently bitten by
      ticks.

PMID- 20684756
TI  - Phylogenetic and regulatory region analysis of Wnt5 genes reveals conservation of
      a regulatory module with putative implication in pancreas development.
AB  - BACKGROUND: Wnt5 genes belong to the large Wnt family, encoding proteins
      implicated into several tumorigenic and developmental processes. Phylogenetic
      analyses showed that Wnt5 gene has been duplicated at the divergence time of
      gnathostomata from agnatha. Interestingly, experimental data for some species
      indicated that only one of the two Wnt5 paralogs participates in the development
      of the endocrine pancreas. The purpose of this paper is to reexamine the
      phylogenetic history of the Wnt5 developmental regulators and investigate the
      functional shift between paralogs through comparative genomics. RESULTS: In this
      study, the phylogeny of Wnt5 genes was investigated in species belonging to
      protostomia and deuterostomia. Furthermore, an in silico regulatory region
      analysis of Wnt5 paralogs was conducted, limited to those species with insulin
      producing cells and pancreas, covering the evolutionary distance from agnatha to
      gnathostomata. Our results confirmed the Wnt5 gene duplication and additionally
      revealed that this duplication event included also the upstream region. Moreover,
      within this latter region, a conserved module was detected to which a complex of
      transcription factors, known to be implicated in embryonic pancreas formation,
      bind. CONCLUSIONS: Results and observations presented in this study, allow us to
      conclude that during evolution, the Wnt5 gene has been duplicated in early
      vertebrates, and that some paralogs conserved a module within their regulatory
      region, functionally related to embryonic development of pancreas. Interestingly,
      our results allowed advancing a possible explanation on why the Wnt5 orthologs do
      not share the same function during pancreas development. As a final remark, we
      suggest that an in silico comparative analysis of regulatory regions, especially
      when associated to published experimental data, represents a powerful approach
      for explaining shift of roles among paralogs.

PMID- 20684757
TI  - Cuticle thickening associated with pyrethroid resistance in the major malaria
      vector Anopheles funestus.
AB  - BACKGROUND: Malaria in South Africa is primarily transmitted by Anopheles
      funestus Giles. Resistance to pyrethroid insecticides in An. funestus in northern
      Kwazulu/Natal, South Africa, and in neighbouring areas of southern Mozambique
      enabled populations of this species to increase their ranges into areas where
      pyrethroids were being exclusively used for malaria control. Pyrethroid
      resistance in southern African An. funestus is primarily conferred by
      monooxygenase enzyme metabolism. However, selection for this resistance mechanism
      is likely to have occurred in conjunction with other factors that improve
      production of the resistance phenotype. A strong candidate is cuticle thickening.
      This is because thicker cuticles lead to slower rates of insecticide absorption,
      which is likely to increase the efficiency of metabolic detoxification. RESULTS:
      Measures of mean cuticle thickness in laboratory samples of female An. funestus
      were obtained using scanning electron microscopy (SEM). These females were drawn
      from a laboratory colony carrying the pyrethroid resistance phenotype at a stable
      rate, but not fixed. Prior to cuticle thickness measurements, these samples were
      characterised as either more or less tolerant to permethrin exposure in one
      experiment, and either permethrin resistant or susceptible in another experiment.
      There was a significant and positive correlation between mean cuticle thickness
      and time to knock down during exposure to permethrin. Mean cuticle thickness was
      significantly greater in those samples characterised either as more tolerant or
      resistant to permethrin exposure compared to those characterised as either less
      tolerant or permethrin susceptible. Further, insecticide susceptible female An.
      funestus have thicker cuticles than their male counterparts. CONCLUSION:
      Pyrethroid tolerant or resistant An. funestus females are likely to have thicker
      cuticles than less tolerant or susceptible females, and females generally have
      thicker cuticles than males. In pyrethroid resistant An. funestus, this increase
      in cuticle thickness is likely to have developed as an auxiliary to the primary
      mode of pyrethroid resistance which is based on enzyme-mediated detoxification.

PMID- 20684758
TI  - Central venous oxygen saturation and blood lactate levels during cardiopulmonary
      bypass are associated with outcome after pediatric cardiac surgery.
AB  - INTRODUCTION: Central venous oxygen saturation and blood lactate are different
      indices of the adequacy of oxygen delivery to the oxygen needs. In pediatric
      cardiac surgery, lactate level and kinetics during and after cardiopulmonary
      bypass are associated with outcome variables. The aim of this study was to
      explore the hypothesis that the lowest central venous oxygen saturation and the
      peak lactate value during cardiopulmonary bypass, used alone or in combination,
      may be predictive of major morbidity and mortality in pediatric cardiac surgery.
      METHODS: We conducted a retrospective analysis of 256 pediatric (younger than 6
      years) patients who had undergone cardiac surgery with continuous monitoring of
      central venous oxygen saturation and serial measurement of blood lactate.
      RESULTS: Peak lactate was significantly increased when the nadir central venous
      oxygen saturation was < 68%. Both nadir central venous oxygen saturation and peak
      lactate during cardiopulmonary bypass were independently associated with major
      morbidity and mortality, with the same accuracy for major morbidity and a higher
      accuracy of peak lactate for mortality. A combined index (central venous oxygen
      saturation < 68% and peak lactate > 3 mmol/L) provided the highest sensitivity
      and specificity for major morbidity, with a positive predictive value of 89%.
      CONCLUSIONS: The combination of a continuous monitoring of central venous oxygen
      saturation and serial measurements of blood lactate during cardiopulmonary bypass
      may offer a predictive index for major morbidity after cardiac operations in
      pediatric patients. This study generates the hypothesis that strategies aimed to
      preserve oxygen delivery during cardiopulmonary bypass may reduce the occurrence
      of low values of central venous oxygen saturation and elevated lactate levels.
      Further studies should consider this hypothesis and take into account other time
      related factors, such as time of exposure to low values of central venous oxygen
      saturation and kinetics of lactate formation.

PMID- 20684759
TI  - Image-based quantitative determination of DNA damage signal reveals a threshold
      for G2 checkpoint activation in response to ionizing radiation.
AB  - BACKGROUND: Proteins involved in the DNA damage response accumulate as
      microscopically-visible nuclear foci on the chromatin flanking DNA double-strand
      breaks (DSBs). As growth of ionizing radiation (IR)-induced foci amplifies the
      ATM-dependent DNA damage signal, the formation of discrete foci plays a crucial
      role in cell cycle checkpoint activation, especially in cells exposed to lower
      doses of IR. However, there is no quantitative parameter for the foci which
      considers both the number and their size. Therefore, we have developed a novel
      parameter for DNA damage signal based on the image analysis of the foci and
      quantified the amount of the signal sufficient for G2 arrest. RESULTS: The
      parameter that we have developed here was designated as SOID. SOID is an
      abbreviation of Sum Of Integrated Density, which represents the sum of
      fluorescence of each focus within one nucleus. The SOID was calculated for
      individual nucleus as the sum of (area (total pixel numbers) of each focus) x
      (mean fluorescence intensity per pixel of each focus). Therefore, the SOID
      accounts for the number, size, and fluorescence density of IR-induced foci, and
      the parameter reflects the flux of DNA damage signal much more accurately than
      foci number. Using very low doses of X-rays, we performed a "two-way" comparison
      of SOID of Ser139-phosphorylated histone H2AX foci between G2-arrested cells and
      mitosis-progressing cells, and between mitosis-progressing cells in the presence
      or absence of ATM or Chk1/2 inhibitor, both of which abrogate IR-induced G2/M
      checkpoint. The analysis revealed that there was a threshold of DNA damage signal
      for G2 arrest, which was around 4000~5000 SOID. G2 cells with < 4000 SOID were
      neglected by G2/M checkpoint, and thus, the cells could progress to mitosis.
      Chromosome analysis revealed that the checkpoint-neglected and mitosis
      progressing cells had approximately two chromatid breaks on average, indicating
      that 4000~5000 SOID was equivalent to a few DNA double strand breaks.
      CONCLUSIONS: We developed a novel parameter for quantitative analysis of DNA
      damage signal, and we determined the threshold of DNA damage signal for IR
      induced G2 arrest, which was represented by 4000~5000 SOID. The present study
      emphasizes that not only the foci number but also the size of the foci must be
      taken into consideration for the proper quantification of DNA damage signal.

PMID- 20684760
TI  - High rate of loss to clinical follow up among African HIV-infected patients
      attending a London clinic: a retrospective analysis of a clinical cohort.
AB  - BACKGROUND: Long-term regular clinic follow up is an important component of HIV
      care. We determined the frequency and characteristics of HIV-infected patients
      lost to follow up from a London HIV clinic, and factors associated with loss to
      all HIV follow up in the UK. METHODS: We identified 1859 HIV-infected adults who
      had registered and attended a London clinic on one or more occasions between
      January 1997 and December 2005. Loss to follow up was defined as clinic non
      attendance for one or more years. Through anonymized linkage with the Survey of
      Prevalent HIV Infections Diagnosed and Health Protection Scotland, national
      databases of all HIV patients in care in the UK up to December 2006, loss-to
      follow-up patients were categorized as Transfers (subsequently received care at
      another UK HIV clinic) or UKLFU (no record of subsequent attendance at any HIV
      clinic in the UK). Logistic regression analysis was used to identify factors
      associated with UKLFU for those both on highly active antiretroviral therapy
      (HAART) and not on HAART. RESULTS: In total, 722 (38.8%) of 1859 patients were
      defined as lost to follow up. Of these, 347 (48.1%) were Transfers and 375
      (51.9%), or 20.2% of all patients, were UKLFU. Overall, 11.9% of all patients
      receiving HAART, and 32.2% not receiving HAART were UKLFU. Among those on HAART,
      risk factors for UKLFU were: African heterosexual female (OR = 2.22, 95% CI: 1.11
      4.56) versus white men who have sex with men; earlier year of HIV clinic
      registration (1997-1999 OR: 3.51, 95% CI: 1.97-6.26; 2000-02 OR: 2.49, 95% CI:
      1.43-4.32 vs. 2003-2005); CD4 count of < 200 versus > 350 cells/mm3 (OR = 1.99,
      95% CI:1.05-3.74); and a detectable viral load of > 400 copies/ml (OR = 5.03, 95%
      CI: 2.95-8.57 vs. <or= 400 copies/ml) at last clinic visit.Among those not
      receiving HAART, factors were: African heterosexual male (OR = 3.91, 95% CI: 1.77
      8.64) versus white men who have sex with men; earlier HIV clinic registration
      (2000-2002 OR: 2.91, 95% CI: 1.77-4.78; 1997-1999: OR: 5.26, 95% CI: 2.71-10.19);
      and a CD4 count of < 200 cells/mm3 (OR: 3.24, 95% CI: 1.49-7.04). CONCLUSIONS:
      One in five HIV-infected patients (one in three not on HAART and one in nine on
      HAART) from a London clinic were lost to all clinical follow up in the UK. Black
      African ethnicity, earlier year of clinic registration and advanced immunological
      suppression were the most important predictors of UKLFU. There is a need for all
      HIV clinics to establish systems for monitoring and tracing loss-to-follow-up
      patients, and to implement strategies for improving retention in care.

PMID- 20684761
TI  - An interactive surgical planning tool for acetabular fractures: initial results.
AB  - BACKGROUND: Acetabular fractures still are among the most challenging fractures
      to treat because of complex anatomy, involved surgical access to fracture sites
      and the relatively low incidence of these lesions. Proper evaluation and surgical
      planning is necessary to achieve anatomic reduction of the articular surface and
      stable fixation of the pelvic ring. The goal of this study was to test the
      feasibility of preoperative surgical planning in acetabular fractures using a new
      prototype planning tool based on an interactive virtual reality-style
      environment. METHODS: 7 patients (5 male and 2 female; median age 53 y (25 to 92
      y)) with an acetabular fracture were prospectively included. Exclusion criterions
      were simple wall fractures, cases with anticipated surgical dislocation of the
      femoral head for joint debridement and accurate fracture reduction. According to
      the Letournel classification 4 cases had two column fractures, 2 cases had
      anterior column fractures and 1 case had a T-shaped fracture including a
      posterior wall fracture.The workflow included following steps: (1) Formation of a
      patient-specific bone model from preoperative computed tomography scans, (2)
      interactive virtual fracture reduction with visuo-haptic feedback, (3) virtual
      fracture fixation using common osteosynthesis implants and (4) measurement of
      implant position relative to landmarks. The surgeon manually contoured
      osteosynthesis plates preoperatively according to the virtually defined
      deformation. Screenshots including all measurements for the OR were available.The
      tool was validated comparing the preoperative planning and postoperative results
      by 3D-superimposition. RESULTS: Preoperative planning was feasible in all cases.
      In 6 of 7 cases superimposition of preoperative planning and postoperative follow
      up CT showed a good to excellent correlation. In one case part of the procedure
      had to be changed due to impossibility of fracture reduction from an ilioinguinal
      approach. In 3 cases with osteopenic bone patient-specific prebent fixation
      plates were helpful in guiding fracture reduction. Additionally, anatomical
      landmark based measurements were helpful for intraoperative navigation.
      CONCLUSION: The presented prototype planning tool for pelvic surgery was
      successfully integrated in a clinical workflow to improve patient-specific
      preoperative planning, giving visual and haptic information about the injury and
      allowing a patient-specific adaptation of osteosynthesis implants to the
      virtually reduced pelvis.

PMID- 20684762
TI  - Leiomyoma of the bladder presenting as acute urinary retention in a female
      patient: urodynamic analysis of lower urinary tract symptom; a case report.
AB  - BACKGROUND: Most bladder tumors are derived from the urothelium. Benign
      mesenchymal tumors are rare. Leiomyoma of the bladder is the most common benign
      neoplasm. We present a case of leiomyoma of the bladder presenting with acute
      urinary retention in a female patient and report on the post-operative change in
      urodynamic findings. To our knowledge, few cases of this kind have been reported.
      CASE PRESENTATION: A 56-year-old woman presented with acute urinary retention.
      Evaluations including ultrasound, magnetic resonance imaging, cystoscopy, and
      urodynamics contributed to a diagnosis of leiomyoma of the bladder. Various
      medications were ineffective for solving her lower urinary tract symptoms;
      therefore, a transurethral resection was performed. The final pathological report
      was leiomyoma. After the operation, her symptoms resolved; this improvement was
      confirmed by an urodynamic analysis. The postoperative urodynamics demonstrated a
      lower frequency of detrusor overactivity during filling cystometry and an
      increase in the uroflow rate, with reduced detrusor pressure in a pressure flow
      study. CONCLUSIONS: Leiomyoma of the bladder can cause female outlet obstruction.
      A review of the literature and disease management is discussed.

PMID- 20684763
TI  - Cathepsin B inhibition interferes with metastatic potential of human melanoma: an
      in vitro and in vivo study.
AB  - BACKGROUND: Cathepsins represent a group of proteases involved in determining the
      metastatic potential of cancer cells. Among these are cysteinyl- (e.g. cathepsin
      B and cathepsin L) and aspartyl-proteases (e.g. cathepsin D), normally present
      inside the lysosomes as inactive proenzymes. Once released in the extracellular
      space, cathepsins contribute to metastatic potential by facilitating cell
      migration and invasiveness. RESULTS: In the present work we first evaluated, by
      in vitro procedures, the role of cathepsins B, L and D, in the remodeling,
      spreading and invasiveness of eight different cell lines: four primary and four
      metastatic melanoma cell lines. Among these, we considered two cell lines derived
      from a primary cutaneous melanoma and from a supraclavicular lymph node
      metastasis of the same patient. To this purpose, the effects of specific chemical
      inhibitors of these proteases, i.e. CA-074 and CA-074Me for cathepsin B,
      Cathepsin inhibitor II for cathepsin L, and Pepstatin A for cathepsin D, were
      evaluated. In addition, we also analyzed the effects of the biological inhibitors
      of these cathepsins, i.e. specific antibodies, on cell invasiveness. We found
      that i) cathepsin B, but not cathepsins L and D, was highly expressed at the
      surface of metastatic but not of primary melanoma cell lines and that ii) CA-074,
      or specific antibodies to cathepsin B, hindered metastatic cell spreading and
      dissemination, whereas neither chemical nor biological inhibitors of cathepsins D
      and L had significant effects. Accordingly, in vivo studies, i.e. in murine
      xenografts, demonstrated that CA-074 significantly reduced human melanoma growth
      and the number of artificial lung metastases. CONCLUSIONS: These results suggest
      a reappraisal of the use of cathepsin B inhibitors (either chemical or
      biological) as innovative strategy in the management of metastatic melanoma
      disease.

PMID- 20684764
TI  - Ownership and usage of insecticide-treated bed nets after free distribution via a
      voucher system in two provinces of Mozambique.
AB  - BACKGROUND: Insecticide-treated bed nets (ITNs) are an efficacious intervention
      for malaria prevention. During a national immunization campaign in Mozambique,
      vouchers, which were to be redeemed at a later date for free ITNs, were
      distributed in Manica and Sofala provinces. A survey to evaluate ITN ownership
      and usage post-campaign was conducted. METHODS: Four districts in each province
      and four enumeration areas (EAs) in each district were selected using probability
      proportional to size. Within each EA, 32 households (HHs) were selected using a
      simple random sample. Interviews to assess ownership and usage were conducted in
      each of the selected HHs using personal digital assistants. RESULTS: Valid
      interviews were completed for 947 (92.5%) (440 in Manica and 507 in Sofala) of
      the 1,024 selected HHs. Among participating HHs, 65.0% in Manica and 63.1% in
      Sofala reported that at least one child under five years of age slept in the
      house the previous night. HH ownership of at least one bed net of any kind was
      20.6% (95% confidence interval [CI]: 7.9%-43.6%) and 35.6% (95% CI: 27.8%-44.3%)
      pre-campaign; and 55.1% (95% CI: 43.6%-66.1%) and 59.6 (95% CI: 42.4%-74.7%) post
      campaign in Manica and Sofala, respectively. Post-campaign HH ownership of at
      least one ITN was 50.2% (95% CI: 41.8%-58.5%) for both provinces combined. In
      addition, 60.3% (95% CI: 50.6%-69.2%) of children under five years of age slept
      under an ITN the previous night. CONCLUSIONS: This ITN distribution increased bed
      net ownership and usage rates. Integration of ITN distribution with immunization
      campaigns presents an opportunity for reaching malaria control targets and should
      continue to be considered.

PMID- 20684765
TI  - Molecular characterization of genome segments 1 and 3 encoding two capsid
      proteins of Antheraea mylitta cytoplasmic polyhedrosis virus.
AB  - BACKGROUND: Antheraea mylitta cytoplasmic polyhedrosis virus (AmCPV), a cypovirus
      of Reoviridae family, infects Indian non-mulberry silkworm, Antheraea mylitta,
      and contains 11 segmented double stranded RNA (S1-S11) in its genome. Some of its
      genome segments (S2 and S6-S11) have been previously characterized but genome
      segments encoding viral capsid have not been characterized. RESULTS: In this
      study genome segments 1 (S1) and 3 (S3) of AmCPV were converted to cDNA, cloned
      and sequenced. S1 consisted of 3852 nucleotides, with one long ORF of 3735
      nucleotides and could encode a protein of 1245 amino acids with molecular mass of
      approximately 141 kDa. Similarly, S3 consisted of 3784 nucleotides having a long
      ORF of 3630 nucleotides and could encode a protein of 1210 amino acids with
      molecular mass of approximately 137 kDa. BLAST analysis showed 20-22% homology of
      S1 and S3 sequence with spike and capsid proteins, respectively, of other closely
      related cypoviruses like Bombyx mori CPV (BmCPV), Lymantria dispar CPV (LdCPV),
      and Dendrolimus punctatus CPV (DpCPV). The ORFs of S1 and S3 were expressed as
      141 kDa and 137 kDa insoluble His-tagged fusion proteins, respectively, in
      Escherichia coli M15 cells via pQE-30 vector, purified through Ni-NTA
      chromatography and polyclonal antibodies were raised. Immunoblot analysis of
      purified polyhedra, virion particles and virus infected mid-gut cells with the
      raised anti-p137 and anti-p141 antibodies showed specific immunoreactive bands
      and suggest that S1 and S3 may code for viral structural proteins. Expression of
      S1 and S3 ORFs in insect cells via baculovirus recombinants showed to produce
      viral like particles (VLPs) by transmission electron microscopy. Immunogold
      staining showed that S3 encoded proteins self assembled to form viral outer
      capsid and VLPs maintained their stability at different pH in presence of S1
      encoded protein. CONCLUSION: Our results of cloning, sequencing and functional
      analysis of AmCPV S1 and S3 indicate that S3 encoded viral structural proteins
      can self assemble to form viral outer capsid and S1 encoded protein remains
      associated with it as inner capsid to maintain the stability. Further studies
      will help to understand the molecular mechanism of capsid formation during
      cypovirus replication.

PMID- 20684766
TI  - Genome mapping and characterization of the Anopheles gambiae heterochromatin.
AB  - BACKGROUND: Heterochromatin plays an important role in chromosome function and
      gene regulation. Despite the availability of polytene chromosomes and genome
      sequence, the heterochromatin of the major malaria vector Anopheles gambiae has
      not been mapped and characterized. RESULTS: To determine the extent of
      heterochromatin within the An. gambiae genome, genes were physically mapped to
      the euchromatin-heterochromatin transition zone of polytene chromosomes. The
      study found that a minimum of 232 genes reside in 16.6 Mb of mapped
      heterochromatin. Gene ontology analysis revealed that heterochromatin is enriched
      in genes with DNA-binding and regulatory activities. Immunostaining of the An.
      gambiae chromosomes with antibodies against Drosophila melanogaster
      heterochromatin protein 1 (HP1) and the nuclear envelope protein lamin Dm0
      identified the major invariable sites of the proteins' localization in all
      regions of pericentric heterochromatin, diffuse intercalary heterochromatin, and
      euchromatic region 9C of the 2R arm, but not in the compact intercalary
      heterochromatin. To better understand the molecular differences among chromatin
      types, novel Bayesian statistical models were developed to analyze genome
      features. The study found that heterochromatin and euchromatin differ in gene
      density and the coverage of retroelements and segmental duplications. The
      pericentric heterochromatin had the highest coverage of retroelements and tandem
      repeats, while intercalary heterochromatin was enriched with segmental
      duplications. We also provide evidence that the diffuse intercalary
      heterochromatin has a higher coverage of DNA transposable elements,
      minisatellites, and satellites than does the compact intercalary heterochromatin.
      The investigation of 42-Mb assembly of unmapped genomic scaffolds showed that it
      has molecular characteristics similar to cytologically mapped heterochromatin.
      CONCLUSIONS: Our results demonstrate that Anopheles polytene chromosomes and
      whole-genome shotgun assembly render the mapping and characterization of a
      significant part of heterochromatic scaffolds a possibility. These results reveal
      the strong association between characteristics of the genome features and
      morphological types of chromatin. Initial analysis of the An. gambiae
      heterochromatin provides a framework for its functional characterization and
      comparative genomic analyses with other organisms.

PMID- 20684767
TI  - Differential item functioning (DIF) analyses of health-related quality of life
      instruments using logistic regression.
AB  - BACKGROUND: Differential item functioning (DIF) methods can be used to determine
      whether different subgroups respond differently to particular items within a
      health-related quality of life (HRQoL) subscale, after allowing for overall
      subgroup differences in that scale. This article reviews issues that arise when
      testing for DIF in HRQoL instruments. We focus on logistic regression methods,
      which are often used because of their efficiency, simplicity and ease of
      application. METHODS: A review of logistic regression DIF analyses in HRQoL was
      undertaken. Methodological articles from other fields and using other DIF methods
      were also included if considered relevant. RESULTS: There are many competing
      approaches for the conduct of DIF analyses and many criteria for determining what
      constitutes significant DIF. DIF in short scales, as commonly found in HRQL
      instruments, may be more difficult to interpret. Qualitative methods may aid
      interpretation of such DIF analyses. CONCLUSIONS: A number of methodological
      choices must be made when applying logistic regression for DIF analyses, and many
      of these affect the results. We provide recommendations based on reviewing the
      current evidence. Although the focus is on logistic regression, many of our
      results should be applicable to DIF analyses in general. There is a need for more
      empirical and theoretical work in this area.

PMID- 20684768
TI  - Diarrhoea in a large prospective cohort of European travellers to resource
      limited destinations.
AB  - BACKGROUND: Incidence rates of travellers' diarrhoea (TD) need to be updated and
      risk factors are insufficiently known. METHODS: Between July 2006 and January
      2008 adult customers of our Centre for Travel Health travelling to a resource
      limited country for the duration of 1 to 8 weeks were invited to participate in a
      prospective cohort study. They received one questionnaire pre-travel and a second
      one immediately post-travel. First two-week incidence rates were calculated for
      TD episodes and a risk assessment was made including demographic and travel
      related variables, medical history and behavioural factors. RESULTS: Among the
      3100 persons recruited, 2800 could be investigated, resulting in a participation
      rate of 89.2%. The first two-weeks incidence for classic TD was 26.2% (95%CI 24.5
      27.8). The highest rates were found for Central Africa (29.6%, 95% CI 12.4-46.8),
      the Indian subcontinent (26.3%, 95%CI 2.3-30.2) and West Africa (21.5%, 95%CI
      14.9-28.1). Median TD duration was 2 days (range 1-90). The majority treated TD
      with loperamide (57.6%), while a small proportion used probiotics (23.0%) and
      antibiotics (6.8%). Multiple logistic regression analysis on any TD to determine
      risk factors showed that a resolved diarrhoeal episode experienced in the 4
      months pre-travel (OR 2.03, 95%CI 1.59-2.54), antidepressive comedication (OR
      2.11, 95%CI 1.17-3.80), allergic asthma (OR 1.67, 95%CI 1.10-2.54), and reporting
      TD-independent fever (OR 6.56, 95%CI 3.06-14.04) were the most prominent risk
      factors of TD. CONCLUSIONS: TD remains a frequent travel disease, but there is a
      decreasing trend in the incidence rate. Patients with a history of allergic
      asthma, pre-travel diarrhoea, or of TD-independent fever were more likely to
      develop TD while abroad.

PMID- 20684769
TI  - Open source tool for prediction of genome wide protein-protein interaction
      network based on ortholog information.
AB  - BACKGROUND: Protein-protein interactions are crucially important for cellular
      processes. Knowledge of these interactions improves the understanding of cell
      cycle, metabolism, signaling, transport, and secretion. Information about
      interactions can hint at molecular causes of diseases, and can provide clues for
      new therapeutic approaches. Several (usually expensive and time consuming)
      experimental methods can probe protein - protein interactions. Data sets, derived
      from such experiments make the development of prediction methods feasible, and
      make the creation of protein-protein interaction network predicting tools
      possible. METHODS: Here we report the development of a simple open source program
      module (OpenPPI_predictor) that can generate a putative protein-protein
      interaction network for target genomes. This tool uses the orthologous
      interactome network data from a related, experimentally studied organism.
      RESULTS: Results from our predictions can be visualized using the Cytoscape
      visualization software, and can be piped to downstream processing algorithms. We
      have employed our program to predict protein-protein interaction network for the
      human parasite roundworm Brugia malayi, using interactome data from the free
      living nematode Caenorhabditis elegans. AVAILABILITY: The OpenPPI_predictor
      source code is available from http://tools.neb.com/~posfai/.

PMID- 20684770
TI  - Extramammary Paget's disease with the appearance of a nodule: a case report.
AB  - BACKGROUND: Extramammary Paget's disease (EMPD) remains a rare condition with
      only a limited number of cases reported in the literature. EMPD is mainly
      composed of intraepidermal Paget cells, and possesses variable clinical behaviors
      and histological appearances, leading to difficulty in the diagnosis of this
      disease. CASE PRESENTATION: We here report a case of primary EMPD with the
      appearance of a nodule on the background of erythema. Histological assessment
      showed Paget cell infiltration throughout the epidermis with dermal spread. Using
      immunohistochemistry, the expressions of CK7, CK19, CK20, GCDFP-15, CEA, S-100
      protein and bcl-2 were examined to elucidate the cellular differentiation of the
      carcinoma. CONCLUSION: According to the histological assessment, this case was
      diagnosed as primary EMPD with carcinoma cells invading into the dermis, but
      without lymph node infiltration.

PMID- 20684771
TI  - Is the presence of abnormal prion protein in the renal glomeruli of feline
      species presenting with FSE authentic?
AB  - In a recent paper written by Hilbe et al (BMC vet res, 2009), the nature and
      specificity of the prion protein deposition in the kidney of feline species
      affected with feline spongiform encephalopathy (FSE) were clearly considered
      doubtful. This article was brought to our attention because we published several
      years ago an immunodetection of abnormal prion protein in the kidney of a cheetah
      affected with FSE. At this time we were convinced of its specificity but without
      having all the possibilities to demonstrate it. As previously published by
      another group, the presence of abnormal prion protein in some renal glomeruli in
      domestic cats affected with FSE is indeed generally considered as doubtful mainly
      because of low intensity detected in this organ and because control kidneys from
      safe animals present also a weak prion immunolabelling. Here we come back on
      these studies and thought it would be helpful to relay our last data to the
      readers of BMC Vet res for future reference on this subject.Here we come back on
      our material as it is possible to study and demonstrate the specificity of prion
      immunodetection using the PET-Blot method (Paraffin Embedded Tissue--Blot). It is
      admitted that this method allows detecting the Proteinase K (PK) resistant form
      of the abnormal prion protein (PrPres) without any confusion with unspecific
      immunoreaction. We re-analysed the kidney tissue versus adrenal gland and brain
      samples from the same cheetah affected with TSE using this PET-Blot method. The
      PET-Blot analysis revealed specific PrPres detection within the brain, adrenal
      gland and some glomeruli of the kidney, with a complete identicalness compared to
      our previous detection using immunohistochemistry. In conclusion, these new data
      enable us to confirm with assurance the presence of specific abnormal prion
      protein in the adrenal gland and in the kidney of the cheetah affected with FSE.
      It also emphasizes the usefulness for the re-examination of any available tissue
      blocks with the PET-Blot method as a sensitive complementary tool in case of
      doubtful PrP IHC results.

PMID- 20684772
TI  - Endotoxin levels correlate positively with a sedentary lifestyle and negatively
      with highly trained subjects.
AB  - INTRODUCTION: A sedentary lifestyle increases the risk of developing
      cardiovascular disease, obesity, and diabetes. This phenomenon is supported by
      recent studies suggesting a chronic, low-grade inflammation status. Endotoxin
      derived from gut flora may be key to the development of inflammation by
      stimulating the secretion of inflammatory factors. This study aimed to examine
      plasma inflammatory markers and endotoxin levels in individuals with a sedentary
      lifestyle and/or in highly trained subjects at rest. METHODS: Fourteen male
      subjects (sedentary lifestyle n = 7; highly trained subjects n = 7) were
      recruited. Blood samples were collected after an overnight fast (approximately 12
      h). The plasmatic endotoxin, plasminogen activator inhibitor type-1 (PAI-1),
      monocyte chemotactic protein-1 (MCP1), ICAM/CD54, VCAM/CD106 and lipid profile
      levels were determined. RESULTS: Endotoxinemia was lower in the highly trained
      subject group relative to the sedentary subjects (p < 0.002). In addition, we
      observed a positive correlation between endotoxin and PAI-1 (r = 0.85, p <
      0.0001), endotoxin and total cholesterol (r = 0.65; p < 0.01), endotoxin and LDL
      c (r = 0.55; p < 0.049) and endotoxin and TG levels (r = 0.90; p < 0.0001). The
      plasma levels of MCP-1, ICAM/CD54 and VCAM/CD106 did not differ. CONCLUSION:
      These results indicate that a lifestyle associated with high-intensity and high
      volume exercise induces favorable changes in chronic low-grade inflammation
      markers and may reduce the risk for diseases such as obesity, diabetes and
      cardiovascular diseases.

PMID- 20684773
TI  - High-grade endometrial stromal sarcoma presenting in a 28-year-old woman during
      pregnancy: a case report.
AB  - INTRODUCTION: To the best of our knowledge, soft tissue sarcomas have not
      prevously been reported as a complication during pregnancy. CASE PRESENTATION: A
      28-year-old Caucasian woman was diagnosed with a transperitoneal sarcoma during
      pregnancy. Morphological, immunohistochemical, chromosomal and mutational
      analyses pointed towards a high-grade endometrial stromal sarcoma. Although
      surgery and chemotherapy are possible during pregnancy, we were unable to perform
      these in this case. CONCLUSION: The potential to treat gynecological cancer
      during pregnancy should always be assessed individually.

PMID- 20684774
TI  - Systematic analysis of short internal indels and their impact on protein folding.
AB  - BACKGROUND: Protein sequence insertions/deletions (indels) can be introduced
      during evolution or through alternative splicing (AS). Alternative splicing is an
      important biological phenomenon and is considered as the major means of expanding
      structural and functional diversity in eukaryotes. Knowledge of the structural
      changes due to indels is critical to our understanding of the evolution of
      protein structure and function. In addition, it can help us probe the evolution
      of alternative splicing and the diversity of functional isoforms. However, little
      is known about the effects of indels, in particular the ones involving core
      secondary structures, on the folding of protein structures. The long term goal of
      our study is to accurately predict the protein AS isoform structures. As a first
      step towards this goal, we performed a systematic analysis on the structural
      changes caused by short internal indels through mining highly homologous proteins
      in Protein Data Bank (PDB). RESULTS: We compiled a non-redundant dataset of short
      internal indels (2-40 amino acids) from highly homologous protein pairs and
      analyzed the sequence and structural features of the indels. We found that about
      one third of indel residues are in disordered state and majority of the residues
      are exposed to solvent, suggesting that these indels are generally located on the
      surface of proteins. Though naturally occurring indels are fewer than engineered
      ones in the dataset, there are no statistically significant differences in terms
      of amino acid frequencies and secondary structure types between the "Natural"
      indels and "All" indels in the dataset. Structural comparisons show that all the
      protein pairs with short internal indels in the dataset preserve the structural
      folds and about 85% of protein pairs have global RMSDs (root mean square
      deviations) of 2A or less, suggesting that protein structures tend to be
      conserved and can tolerate short insertions and deletions. A few pairs with high
      RMSDs are results of relative domain positions of the proteins, probably due to
      the intrinsically dynamic nature of the proteins. CONCLUSIONS: The analysis
      demonstrated that protein structures have the "plasticity" to tolerate short
      indels. This study can provide valuable guides in modeling protein AS isoform
      structures and homologous proteins with indels through placing the indels at the
      right locations since the accuracy of sequence alignments dictate model qualities
      in homology modeling.

PMID- 20684775
TI  - Foreign body ingestion mimicking irritable bowel syndrome: a case report.
AB  - INTRODUCTION: Foreign body ingestion is associated with a variety of symptoms and
      complications, often mimicking various diseases. This case report describes an
      unusual presentation following foreign body ingestion. CASE PRESENTATION: A 56
      year-old Greek Caucasian woman presented to a primary care setting, in rural
      Crete, Greece, with complaints of abdominal pain, cramping and bloating, for the
      last four months. Alternating constipation and diarrhea was reported. The patient
      had unknowingly ingested a foreign body that resulted in an irritable bowel
      syndrome-like presentation. CONCLUSIONS: This case report emphasizes the need for
      a high index of suspicion from physicians for a wide differential in their
      approach to abdominal complaints, as well as the importance of an individualized
      approach to patients in the setting of clinical medicine.

PMID- 20684776
TI  - R-Roscovitine (Seliciclib) prevents DNA damage-induced cyclin A1 upregulation and
      hinders non-homologous end-joining (NHEJ) DNA repair.
AB  - BACKGROUND: CDK-inhibitors can diminish transcriptional levels of cell cycle
      related cyclins through the inhibition of E2F family members and CDK7 and 9.
      Cyclin A1, an E2F-independent cyclin, is strongly upregulated under genotoxic
      conditions and functionally was shown to increase NHEJ activity. Cyclin A1
      outcompetes with cyclin A2 for CDK2 binding, possibly redirecting its activity
      towards DNA repair. To see if we could therapeutically block this switch, we
      analyzed the effects of the CDK-inhibitor R-Roscovitine on the expression levels
      of cyclin A1 under genotoxic stress and observed subsequent DNA damage and repair
      mechanisms. RESULTS: We found that R-Roscovitine alone was unable to alter cyclin
      A1 transcriptional levels, however it was able to reduce protein expression
      through a proteosome-dependent mechanism. When combined with DNA damaging agents,
      R-Roscovitine was able to prevent the DNA damage-induced upregulation of cyclin
      A1 on a transcriptional and post-transcriptional level. This, moreover resulted
      in a significant decrease in non-homologous end-joining (NHEJ) paired with an
      increase in DNA DSBs and overall DNA damage over time. Furthermore, microarray
      analysis demonstrated that R-Roscovitine affected DNA repair mechanisms in a more
      global fashion. CONCLUSIONS: Our data reveal a new mechanism of action for R
      Roscovitine on DNA repair through the inhibition of the molecular switch between
      cyclin A family members under genotoxic conditions resulting in reduced NHEJ
      capability.

PMID- 20684777
TI  - Alcohol policy enforcement and changes in student drinking rates in a statewide
      public college system: a follow-up study.
AB  - BACKGROUND: Heavy alcohol use among U.S. college students is a major contributor
      to young adult morbidity and mortality. The aim of this study was to examine
      whether college alcohol policy enforcement levels predict changes in student
      drinking and related behaviors in a state system of public colleges and
      universities, following a system-wide change to a stricter policy. METHODS:
      Students and administrators at 11 Massachusetts public colleges/universities
      completed surveys in 1999 (N of students = 1252), one year after the policy
      change, and again in 2001 (N = 1074). We calculated policy enforcement scores for
      each school based on the reports of deans of students, campus security chiefs,
      and students, and examined the correlations between perceived enforcement levels
      and the change in student drinking rates over the subsequent two year period,
      after weighting the 2001 data to adjust for demographic changes in the student
      body. RESULTS: Overall rates of any past-30-days drinking, heavy episodic
      drinking, and usual heavy drinking among past-30-days drinkers were all lower in
      2001 compared to 1999. School-level analyses (N = 11) found deans' baseline
      reports of stricter enforcement were strongly correlated with subsequent declines
      in heavy episodic drinking (Pearson's r = -0.73, p = 0.011). Moreover,
      consistently high enforcement levels across time, as reported by deans, were
      associated with greater declines in heavy episodic drinking. Such relationships
      were not found for students' and security chiefs' reports of enforcement.
      Marijuana use did not rise during this period of decline in heavy drinking.
      CONCLUSIONS: Study findings suggest that stronger enforcement of a stricter
      alcohol policy may be associated with reductions in student heavy drinking rates
      over time. An aggressive enforcement stance by deans may be an important element
      of an effective college alcohol policy.

PMID- 20684778
TI  - Rapid detection of Pseudomonas aeruginosa from positive blood cultures by
      quantitative PCR.
AB  - BACKGROUND: Pseudomonas aeruginosa is responsible for numerous bloodstream
      infections associated with severe adverse outcomes in case of inappropriate
      initial antimicrobial therapy. The present study was aimed to develop a novel
      quantitative PCR (qPCR) assay, using ecfX as the specific target gene, for the
      rapid and accurate identification of P. aeruginosa from positive blood cultures
      (BCs). METHODS: Over the period August 2008 to June 2009, 100 BC bottles positive
      for gram-negative bacilli were tested in order to evaluate performances of the
      qPCR technique with conventional methods as gold standard (i.e. culture and
      phenotypic identification). RESULTS: Thirty-three strains of P. aeruginosa, 53
      strains of Enterobactericaeae, nine strains of Stenotrophomonas maltophilia and
      two other gram-negative species were isolated while 3 BCs were polymicrobial
      including one mixture containing P. aeruginosa. All P. aeruginosa clinical
      isolates were detected by qPCR except a single strain in mixed culture.
      Performances of the qPCR technique were: specificity, 100%; positive predictive
      value, 100%; negative predictive value, 98.5%; and sensitivity, 97%. CONCLUSIONS:
      This reliable technique may offer a rapid (<1.5 h) tool that would help
      clinicians to initiate an appropriate treatment earlier. Further investigations
      are needed to assess the clinical benefit of this novel strategy as compared to
      phenotypic methods.

PMID- 20684779
TI  - Tropheryma whipplei tricuspid endocarditis: a case report and review of the
      literature.
AB  - INTRODUCTION: The main clinical manifestations of Whipple's disease are weight
      loss, arthropathy, diarrhea and abdominal pain. Cardiac involvement is frequently
      described. However, endocarditis is rare and is not usually the initial
      presentation of the disease. To the best of our knowledge, this is the first
      reported case of a patient with Tropheryma whipplei tricuspid endocarditis
      without any other valve involved and not presenting signs of arthralgia and
      abdominal involvement. CASE PRESENTATION: We report a case of a 50-year-old
      Caucasian man with tricuspid endocarditis caused by Tropheryma whipplei, showing
      signs of severe shock and an absence of other more classic clinical signs of
      Whipple's disease, such as arthralgia, abdominal pain and diarrhea. Tropheryma
      whipplei was documented by polymerase chain reaction of the blood and pleural
      fluid. The infection was treated with a combined treatment of doxycycline,
      hydroxychloroquine and sulfamethoxazole-trimethoprim for one year. CONCLUSION:
      Tropheryma whipplei infectious endocarditis should always be considered when
      facing a blood-culture negative endocarditis particularly in right-sided valves.
      Although not standardized yet, treatment of Tropheryma whipplei endocarditis
      should probably include a bactericidal antibiotic (such as doxycycline) and
      should be given over a prolonged period of time (a minimum of one year).

PMID- 20684780
TI  - Cardiac tamponade mimicking tuberculous pericarditis as the initial presentation
      of chronic lymphocytic leukemia in a 58-year-old woman: a case report.
AB  - INTRODUCTION: Chronic lymphocytic leukemia is an indolent disease that often
      presents with complaints of lymphadenopathy or is detected as an incidental
      laboratory finding. It is rarely considered in the differential diagnosis of
      patients presenting with tamponade or a large, bloody pericardial effusion. In
      patients without known cancer, a large, bloody pericardial effusion raises the
      possibility of tuberculosis, particularly in patients from endemic areas.
      However, the signs, symptoms and laboratory findings of pericarditis related to
      chronic lymphocytic leukemia can mimic tuberculosis. CASE PRESENTATION: We report
      the case of a 58-year-old African American-Nigerian woman with a history of
      travel to Nigeria and a positive tuberculin skin test who presented with cardiac
      tamponade. She had a mild fever, lymphocytosis and a bloody pericardial effusion,
      but cultures and stains were negative for acid-fast bacteria. Assessment of blood
      by flow cytometry and pericardial biopsy by immunohistochemistry revealed CD5 (+)
      and CD20 (+) lymphocytes in both tissues, demonstrating this to be an unusual
      manifestation of early stage chronic lymphocytic leukemia. CONCLUSION: Although
      most malignancies that involve the pericardium clinically manifest elsewhere
      before presenting with tamponade, this case illustrates the potential for early
      stage chronic lymphocytic leukemia to present as a large pericardial effusion
      with tamponade. Moreover, the presentation mimicked tuberculosis. This case also
      demonstrates that it is possible to treat chronic lymphocytic leukemia-related
      pericardial tamponade by removal of the fluid without chemotherapy.

PMID- 20684781
TI  - Cord blood versus age 5 mononuclear cell proliferation on IgE and asthma.
AB  - BACKGROUND: Fetal immune responses following exposure of mothers to allergens
      during pregnancy may influence the subsequent risk of childhood asthma. However,
      the association of allergen-induced cord blood mononuclear cell (CBMC)
      proliferation and cytokine production with later allergic immune responses and
      asthma has been controversial. Our objective was to compare indoor allergen
      induced CBMC with age 5 peripheral blood mononuclear cell (PBMC) proliferation
      and determine which may be associated with age 5 allergic immune responses and
      asthma in an inner city cohort. METHODS: As part of an ongoing cohort study of
      the Columbia Center for Children's Environmental Health (CCCEH), CBMCs and age 5
      PBMCs were cultured with cockroach, mouse, and dust mite protein extracts. CBMC
      proliferation and cytokine (IL-5 and IFN-gamma) responses, and age 5 PBMC
      proliferation responses, were compared to anti-cockroach, anti-mouse, and anti
      dust mite IgE levels, wheeze, cough, eczema and asthma. RESULTS: Correlations
      between CBMC and age 5 PBMC proliferation in response to cockroach, mouse, and
      dust mite antigens were nonsignificant. Cockroach-, mouse-, and dust mite-induced
      CBMC proliferation and cytokine responses were not associated with allergen
      specific IgE at ages 2, 3, and 5, or with asthma and eczema at age 5. However,
      after adjusting for potential confounders, age 5 cockroach-induced PBMC
      proliferation was associated with anti-cockroach IgE, total IgE, and asthma (p <
      0.05). CONCLUSION: In contrast to allergen-induced CBMC proliferation, age 5
      cockroach-induced PBMC proliferation was associated with age 5 specific and total
      IgE, and asthma, in an inner-city cohort where cockroach allergens are prevalent
      and exposure can be high.

PMID- 20684782
TI  - Selective control of amino acid metabolism by the GCN2 eIF2 kinase pathway in
      Saccharomyces cerevisiae.
AB  - BACKGROUND: When eukaryotic cells are deprived of amino acids, uncharged tRNAs
      accumulate and activate the conserved GCN2 protein kinase. Activated Gcn2p up
      regulates the general amino acid control pathway through phosphorylation of the
      translational initiation factor eIF2. In Saccharomyces cerevisiae, Gcn2p is the
      only kinase that phosphorylates eIF2 to regulate translation through this
      mechanism. We addressed changes in yeast growth and tRNA aminoacylation, or
      charging, during amino acid depletion in the presence and absence of GCN2. tRNA
      charging was measured using a microarray technique which simultaneously measures
      all cytosolic tRNAs. A fully prototrophic strain, and its isogenic gcn2 Delta
      counterpart, were used to study depletion for each of the 20 amino acids, with a
      focus on Trp, Arg, His and Leu, which are metabolically distinct and together
      provide a good overview on amino acid metabolism. RESULTS: While the wild-type
      strain had no observable phenotype upon depletion for any amino acid, the gcn2
      Delta strain showed slow growth in media devoid of only Trp or Arg. Consistent
      with the growth phenotypes, profiles of genome-wide tRNA charging revealed
      significant decrease in cognate tRNA charging only in the gcn2 Delta strain upon
      depletion for Trp or Arg. In contrast, there was no change in tRNA charging
      during His and Leu depletion in either the wild-type or gcn2 Delta strains,
      consistent with the null effect on growth during loss of these amino acids. We
      determined that the growth phenotype of Trp depletion is derived from feedback
      inhibition of aromatic amino acid biosynthesis. By removing Phe and Tyr from the
      media in addition to Trp, regular growth was restored and tRNATrp charging no
      longer decreased. The growth phenotype of Arg depletion is derived from
      unbalanced nitrogen metabolism. By supplementing ornithine upon Arg depletion,
      both growth and tRNAArg charging were partially restored. CONCLUSION: Under mild
      stress conditions the basal activity of Gcn2p is sufficient to allow for proper
      adaptation to amino acid depletion. This study highlights the importance of the
      GCN2 eIF2 kinase pathway for maintaining metabolic homeostasis, contributing to
      appropriate tRNA charging and growth adaptation in response to culture conditions
      deficient for the central amino acids, tryptophan and arginine.

PMID- 20684783
TI  - Ten-year audit of Lichtenstein hernioplasty under local anaesthesia performed by
      surgical residents.
AB  - BACKGROUND: To analyse in a prospective trial the long-term results of
      Lichtenstein hernioplasty performed by surgical trainees. METHODS: Training of
      tension-free Lichtenstein hernia operation was started in our ambulatory unit as
      an outpatient procedure under local anaesthesia in 1996. After performing 36
      teaching operations together with residents and their supervising specialist, 281
      patients were operated during 1996-2000 either by one senior consultant (n = 141)
      or by 12 surgical trainees (n = 140). After 10 years, 247 (88%) patients were
      available for the long-term assessment. RESULTS: After one month postoperatively,
      the rate of wound infections (consultant 1.1%, residents 0.7%) and hematomas
      (consultant 1.1%, residents 3.0%) were low and not related to surgeon's training
      level (ns). Only 6 (2.1%) clinically evident recurrences were found after 10
      years: two after specialist repair and four after trainee repair (ns). Although
      one third of the patients reported some discomfort after 3 and 10 years, 93-95%
      of the patients were very satisfied with the operation, with no statistical
      difference between the surgeons. CONCLUSION: Ambulatory open mesh repair under
      local anaesthesia was a safe operation and the long-term results were acceptable
      among the patients operated by surgical trainees.

PMID- 20684784
TI  - Splenic artery embolization in a woman with bleeding gastric varices and splenic
      vein thrombosis: a case report.
AB  - INTRODUCTION: Gastric variceal bleeding due to splenic vein thrombosis is a life
      threatening situation and is often difficult to manage by endoscopy. In the worst
      cases, an emergency splenectomy may be required to stop variceal bleeding. CASE
      PRESENTATION: We report the case of a 60-year-old Caucasian woman with bleeding
      gastric varices secondary to splenic vein thrombosis treated by splenic artery
      embolization. Successful embolization was performed by depositing coils into the
      splenic artery resulting in cessation of variceal bleeding. After embolization
      there was no recurrence of bleeding. CONCLUSION: Splenic artery embolization can
      be an effective and definite treatment for variceal bleeding secondary to splenic
      vein thrombosis.

PMID- 20684785
TI  - The effect of prior assumptions over the weights in BayesPI with application to
      study protein-DNA interactions from ChIP-based high-throughput data.
AB  - BACKGROUND: To further understand the implementation of hyperparameters re
      estimation technique in Bayesian hierarchical model, we added two more prior
      assumptions over the weight in BayesPI, namely Laplace prior and Cauchy prior, by
      using the evidence approximation method. In addition, we divided hyperparameter
      (regularization constants alpha of the model) into multiple distinct classes
      based on either the structure of the neural networks or the property of the
      weights. RESULTS: The newly implemented BayesPI was tested on both synthetic and
      real ChIP-based high-throughput datasets to identify the corresponding protein
      binding energy matrices. The results obtained were encouraging: 1) there was a
      minor effect on the quality of predictions when prior assumptions over the
      weights were altered (e.g. the prior probability distributions to the weights and
      the number of classes to the hyperparameters) in BayesPI; 2) however, there was a
      significant impact on the computational speed when tuning the weight prior in the
      model: for example, BayesPI with a Laplace weight prior achieved the best
      performance with regard to both the computational speed and the prediction
      accuracy. CONCLUSIONS: From this study, we learned that it is absolutely
      necessary to try different prior assumptions over the weights in Bayesian
      hierarchical model to design an efficient learning algorithm, though the quality
      of the final results may not be associated with such changes. In future, the
      evidence approximation method can be an alternative to Monte Carlo methods for
      computational implementation of Bayesian hierarchical model.

PMID- 20684786
TI  - Evaluation of a system of structured, pro-active care for chronic depression in
      primary care: a randomised controlled trial.
AB  - BACKGROUND: People with chronic depression are frequently lost from effective
      care, with resulting psychological, physical and social morbidity and
      considerable social and financial societal costs. This randomised controlled
      trial will evaluate whether regular structured practice nurse reviews lead to
      better mental health and social outcomes for these patients and will assess the
      cost-effectiveness of the structured reviews compared to usual care.The
      hypothesis is that structured, pro-active care of patients with chronic
      depression in primary care will lead to a cost-effective improvement in medical
      and social outcomes when compared with usual general practitioner (GP) care.
      METHODS/DESIGN: Participants were recruited from 42 general practices throughout
      the United Kingdom. Eligible participants had to have a history of chronic major
      depression, recurrent major depression or chronic dsythymia confirmed using the
      Composite International Diagnostic Interview (CIDI). They also needed to score 14
      or above on the Beck Depression Inventory (BDI-II) at recruitment.Once consented,
      participants were randomised to treatment as usual from their general practice
      (controls) or the practice nurse led intervention. The intervention includes a
      specially prepared education booklet and a comprehensive baseline assessment of
      participants' mood and any associated physical and psycho-social factors,
      followed by regular 3 monthly reviews by the nurse over the 2 year study period.
      At these appointments intervention participants' mood will be reviewed, together
      with their current pharmacological and psychological treatments and any relevant
      social factors, with the nurse suggesting possible amendments according to
      evidence based guidelines. This is a chronic disease management model, similar to
      that used for other long-term conditions in primary care.The primary outcome is
      the BDI-II, measured at baseline and 6 monthly by self-complete postal
      questionnaire. Secondary outcomes collected by self-complete questionnaire at
      baseline and 2 years include social functioning, quality of life and data for the
      economic analyses. Health service data will be collected from GP notes for the 24
      months before recruitment and the 24 months of the study. DISCUSSION: 558
      participants were recruited, 282 to the intervention and 276 to the control arm.
      The majority were recruited via practice database searches using relevant READ
      codes. TRIAL REGISTRATION: ISRCTN36610074.

PMID- 20684787
TI  - Nonparametric identification of regulatory interactions from spatial and temporal
      gene expression data.
AB  - BACKGROUND: The correlation between the expression levels of transcription
      factors and their target genes can be used to infer interactions within animal
      regulatory networks, but current methods are limited in their ability to make
      correct predictions. RESULTS: Here we describe a novel approach which uses
      nonparametric statistics to generate ordinary differential equation (ODE) models
      from expression data. Compared to other dynamical methods, our approach requires
      minimal information about the mathematical structure of the ODE; it does not use
      qualitative descriptions of interactions within the network; and it employs new
      statistics to protect against over-fitting. It generates spatio-temporal maps of
      factor activity, highlighting the times and spatial locations at which different
      regulators might affect target gene expression levels. We identify an ODE model
      for eve mRNA pattern formation in the Drosophila melanogaster blastoderm and show
      that this reproduces the experimental patterns well. Compared to a non-dynamic,
      spatial-correlation model, our ODE gives 59% better agreement to the
      experimentally measured pattern. Our model suggests that protein factors
      frequently have the potential to behave as both an activator and inhibitor for
      the same cis-regulatory module depending on the factors' concentration, and
      implies different modes of activation and repression. CONCLUSIONS: Our method
      provides an objective quantification of the regulatory potential of transcription
      factors in a network, is suitable for both low- and moderate-dimensional gene
      expression datasets, and includes improvements over existing dynamic and static
      models.

PMID- 20684788
TI  - Silent onset of postmenopausal endometriosis in a woman with renal failure in
      hormone replacement therapy: a case report.
AB  - INTRODUCTION: Postmenopausal endometriosis is a rare form of a common disease,
      since the absence of estrogenic hormone production should halt disease
      progression. CASE PRESENTATION: We present the case of a 54-year-old Italian
      Caucasian woman in surgical menopause with a history of ovarian endometriosis,
      who underwent voluntary hormone replacement therapy for seven years. She
      developed postrenal renal failure due to bilateral compression of the pelvic
      ureteral tract caused by two large, deeply infiltrating endometriotic nodules
      with no pelvic pain. She underwent operative laparoscopy with adhesiolysis of
      enteroenteric adhesions and excision of the endometriotic nodules encompassing
      the juxtavesical tract of the ureters, without obtaining improvement of renal
      failure. CONCLUSION: Postmenopausal endometriosis can manifest itself in an
      unpredictable and potentially very serious manner. It is therefore important to
      carefully evaluate the risks and benefits of administering hormone replacement
      therapy to patients with previous endometriosis.

PMID- 20684789
TI  - Physical activity interventions to improve daily walking activity in cancer
      survivors.
AB  - BACKGROUND: Cancer patients may benefit from physical exercise programs. It is
      unclear, however, how sustained levels of physical activity are best achieved in
      this population. A systematic review was performed to summarize the current
      evidence of the effect of physical activity interventions on daily walking
      activity enhancement in cancer survivors, and to review the literature for its
      methodological quality. METHODS: A search in Medline, PEDro and the Cochrane
      databases was performed for English literature citations (randomized controlled
      trials; 'RCTs'). In a first step, one reviewer abstracted data from the included
      studies on patients, physical activity interventions and outcomes. Two
      independent reviewers reviewed the methodological quality of these studies. Data
      were pooled using random-effects calculations. RESULTS: Our search identified 201
      citations. Five RCTs that reported changes in daily step activity over time were
      identified, and were reviewed for methodological quality and substantive results.
      The median score across studies for methodological quality based on the PEDro
      criteria was 8. These 5 RCTs evaluated 660 participants with a mean age of 53.6
      (SD 4.2) years. The mean change in daily step activity for patients with a
      physical exercise intervention was 526 daily steps (SD 537), with a range from 
      92 to 1299 daily steps. The data of three studies reporting the effect of
      combined physical activity and counseling on daily walking activity in breast
      cancer survivors were pooled, however; the I(2) was 79%, indicating statistical
      heterogeneity between the three trials. CONCLUSION: The 5 RCTs reviewed were of
      good methodological quality. Together they suggest that combined physical
      activity and counseling improves daily step activity in (breast) cancer
      survivors. Studies that define a step goal appear to be more effective in
      improving daily walking activity than studies that do not do so. However, the
      current results should be interpreted with caution because of the observed
      clinical and statistical heterogeneity. Future studies are warranted to evaluate
      the effects of goal targeted physical activity, with or without counseling, on
      daily walking in various cancer populations.

PMID- 20684791
TI  - Recurrent advanced colonic cancer occurring 11 years after initial endoscopic
      piecemeal resection: a case report.
AB  - BACKGROUND: The high frequency of local recurrence occurring after endoscopic
      piecemeal resection (EPMR) for large colorectal tumors is a serious problem.
      However, almost all of these cases of local recurrence can be detected within 1
      year and cured by additional endoscopic resection. We report a rare case of
      recurrent advanced colonic cancer diagnosed 11 years after initial EPMR
      treatment. CASE PRESENTATION: A 65-year-old male was diagnosed with a sigmoid
      colon lesion following a routine health check-up. Total colonoscopy revealed a 12
      mm type 0-Is lesion in the sigmoid colon, which was diagnosed as an adenoma or
      intramucosal cancer and treated by EPMR in 1996. The post-resection defect was
      closed completely using metallic endoclips to avoid delayed bleeding. In 2007, at
      the third follow up, colonoscopy revealed a 20 mm submucosal tumor (SMT) like
      recurrence at the site of the previous EPMR. The recurrent lesion was treated by
      laparoscopic assisted sigmoidectomy with lymph node dissection. CONCLUSION: When
      it is difficult to evaluate the depth and margins of resected tumors following
      EPMR, it is important that the defect is not closed in order to avoid tumor
      implantation, missing residual lesions and to enable earlier detection of
      recurrence. It is crucial that the optimal follow-up protocol for EPMR cases is
      clarified, particularly how often and for how long they should be followed.

PMID- 20684790
TI  - Spatiotemporal patterns of macrophage migration inhibitory factor (Mif)
      expression in the mouse placenta.
AB  - BACKGROUND: Macrophage migration inhibitory factor (MIF) has special pro
      inflammatory roles, affecting the functions of macrophages and lymphocytes and
      counter-regulating the effects of glucocorticoids on the immune response. The
      conspicuous expression of MIF during human implantation and early embryonic
      development also suggests this factor acts in reproductive functions. The overall
      goal of this study was to evaluate Mif expression by trophoblast and embryo
      placental cells during mouse pregnancy. METHODS: Mif was immunolocalized at
      implantation sites on gestation days (gd) 7.5, 10.5, 13.5 and 17.5. Ectoplacental
      cones and fetal placentas dissected from the maternal tissues were used for
      Western blotting and qRT-PCR assays on the same gestation days. RESULTS: During
      the post-implantation period (gd7.5), trophoblast giant cells showed strong Mif
      reactivity. In later placentation phases (gds 10.5-17.5), Mif appeared to be
      concentrated in the junctional zone and trophoblast giant cells. Mif protein
      expression increased significantly from gd7.5 to 10.5 (p = 0.005) and from gd7.5
      to 13.5 (p = 0.03), remaining at high concentration as gestation proceeded.
      Higher mRNA expression was found on gd10.5 and was significantly different from
      gd13.5 (p = 0.048) and 17.5 (p = 0.009). CONCLUSIONS: The up-regulation of Mif on
      gd10.5 coincides with the stage in which the placenta assumes its three-layered
      organization (giant cells, spongiotrophoblast and labyrinth zones), fetal blood
      circulation begins and population of uNK cells reaches high proportions at the
      maternal counter part of the placenta, suggesting that Mif may play a role in
      either the placentation or in the adaptation of the differentiated placenta to
      the uterus or still in gestational immunomodulatory responses. Moreover, it
      reinforces the possibility of specific activities for Mif at the maternal fetal
      interface.

PMID- 20684792
TI  - Population screening for glucose-6-phosphate dehydrogenase deficiencies in Isabel
      Province, Solomon Islands, using a modified enzyme assay on filter paper dried
      bloodspots.
AB  - BACKGROUND: Glucose-6-phosphate dehydrogenase deficiency poses a significant
      impediment to primaquine use for the elimination of liver stage infection with
      Plasmodium vivax and for gametocyte clearance, because of the risk of life
      threatening haemolytic anaemia that can occur in G6PD deficient patients.
      Although a range of methods for screening G6PD deficiency have been described,
      almost all require skilled personnel, expensive laboratory equipment, freshly
      collected blood, and are time consuming; factors that render them unsuitable for
      mass-screening purposes. METHODS: A published WST8/1-methoxy PMS method was
      adapted to assay G6PD activity in a 96-well format using dried blood spots, and
      used it to undertake population screening within a malaria survey undertaken in
      Isabel Province, Solomon Islands. The assay results were compared to a
      biochemical test and a recently marketed rapid diagnostic test. RESULTS:
      Comparative testing with biochemical and rapid diagnostic test indicated that
      results obtained by filter paper assay were accurate providing that blood spots
      were assayed within 5 days when stored at ambient temperature and 10 days when
      stored at 4 degrees. Screening of 8541 people from 41 villages in Isabel
      Province, Solomon Islands revealed the prevalence of G6PD deficiency as defined
      by enzyme activity < 30% of normal control was 20.3% and a prevalence of severe
      deficiency that would predispose to primaquine-induced hemolysis (WHO Class I-II)
      of 6.9%. CONCLUSIONS: The assay enabled simple and quick semi-quantitative
      population screening in a malaria-endemic region. The study indicated a high
      prevalence of G6PD deficiency in Isabel Province and highlights the critical need
      to consider G6PD deficiency in the context of P. vivax malaria elimination
      strategies in Solomon Islands, particularly in light of the potential role of
      primaquine mass drug administration.

PMID- 20684794
TI  - Environmental, psychological, and social influences on physical activity among
      Japanese adults: structural equation modeling analysis.
AB  - BACKGROUND: An understanding of the contributing factors to be considered when
      examining how individuals engage in physical activity is important for promoting
      population-based physical activity. The environment influences long-term effects
      on population-based health behaviors. Personal variables, such as self-efficacy
      and social support, can act as mediators of the predictive relationship between
      the environment and physical activity. The present study examines the direct and
      indirect effects of environmental, psychological, and social factors on walking,
      moderate-intensity activity excluding walking, and vigorous-intensity activity
      among Japanese adults. METHODS: The participants included 1,928 Japanese adults
      aged 20-79 years. Seven sociodemographic attributes (e.g., gender, age, education
      level, employment status), psychological variables (self-efficacy, pros, and
      cons), social variables (social support), environmental variables (home fitness
      equipment, access to facilities, neighborhood safety, aesthetic sensibilities,
      and frequency of observing others exercising), and the International Physical
      Activity Questionnaire were assessed via an Internet-based survey. Structural
      equation modeling was conducted to determine associations between environmental,
      psychological, and social factors with physical activity. RESULTS: Environmental
      factors could be seen to have indirect effects on physical activity through their
      influence on psychological and social variables such as self-efficacy, pros and
      cons, and social support. The strongest indirect effects could be observed by
      examining the consequences of environmental factors on physical activity through
      cons to self-efficacy. The total effects of environmental factors on physical
      activity were 0.02 on walking, 0.02 on moderate-intensity activity excluding
      walking, and 0.05 on vigorous-intensity activity. CONCLUSIONS: The present study
      indicates that environmental factors had indirect effects on walking, moderate
      intensity activity excluding walking and vigorous-intensity activity among
      Japanese adults, especially through the effects on these factors of self
      efficacy, social support, and pros and cons. The findings of the present study
      imply that intervention strategies to promote more engagement in physical
      activity for population-based health promotion may be necessary.

PMID- 20684793
TI  - PKCalpha-induced drug resistance in pancreatic cancer cells is associated with
      transforming growth factor-beta1.
AB  - BACKGROUND: Drug resistance remains a great challenge in the treatment of
      pancreatic cancer. The goal of this study was to determine whether TGF-beta1 is
      associated with drug resistance in pancreatic cancer. METHODS: Pancreatic cancer
      BxPC3 cells were stably transfected with TGF-beta1 cDNA. Cellular morphology and
      cell cycle were determined and the suppressive subtracted hybridization (SSH)
      assay was performed to identify differentially expressed genes induced by TGF
      beta1. Western blotting and immunohistochemistry were used to detect expression
      of TGF-beta1-related genes in the cells and tissue samples. After that, the cells
      were further treated with an anti-cancer drug (e.g., cisplatin) after pre
      incubated with the recombinant TGF-beta1 plus PKCalpha inhibitor Go6976. TGF
      beta1 type II receptor, TbetaRII was also knocked down using TbetaRII siRNA to
      assess the effects of these drugs in the cells. Cell viability was assessed by
      MTT assay. RESULTS: Overexpression of TGF-beta1 leads to a markedly increased
      invasion potential but a reduced growth rate in BxPC3 cells. Recombinant TGF
      beta1 protein increases expression of PKCalpha in BxPC3 cells, a result that we
      confirmed by SSH. Moreover, TGF-beta1 reduced the sensitivity of BxPC3 cells to
      cisplatin treatment, and this was mediated by upregulation of PKCalpha. However,
      blockage of PKCalpha with Go6976 and TbetaRII with siRNA reversed the resistance
      of BxPC3 cells to gemcitabine, even in the presence of TGF-beta1.
      Immunohistochemical data show that pancreatic cancers overexpress TGF-beta1 and P
      gp relative to normal tissues. In addition, TGF-beta1 expression is associated
      with P-gp and membranous PKCalpha expression in pancreatic cancer. CONCLUSIONS:
      TGF-beta1-induced drug resistance in pancreatic cancer cells was associated with
      PKCalpha expression. The PKCalpha inhibitor Go6976 could be a promising agent to
      sensitize pancreatic cancer cells to chemotherapy.

PMID- 20684795
TI  - Anticancer activity of a sub-fraction of dichloromethane extract of Strobilanthes
      crispus on human breast and prostate cancer cells in vitro.
AB  - BACKGROUND: The leaves of Strobilanthes crispus (S. crispus) which is native to
      the regions of Madagascar to the Malay Archipelago, are used in folk medicine for
      their antidiabetic, diuretic, anticancer and blood pressure lowering properties.
      Crude extracts of this plant have been found to be cytotoxic to human cancer cell
      lines and protective against chemically-induced hepatocarcinogenesis in rats. In
      this study, the cytotoxicity of various sub-fractions of dichloromethane extract
      isolated from the leaves of S. crispus was determined and the anticancer activity
      of one of the bioactive sub-fractions, SC/D-F9, was further analysed in breast
      and prostate cancer cell lines. METHODS: The dichloromethane extract of S.
      crispus was chromatographed on silica gel by flash column chromatography. The
      ability of the various sub-fractions obtained to induce cell death of MCF-7, MDA
      MB-231, PC-3 and DU-145 cell lines was determined using the LDH assay. The dose
      response effect and the EC50 values of the active sub-fraction, SC/D-F9, were
      determined. Apoptosis was detected using Annexin V antibody and propidium iodide
      staining and analysed by fluorescence microscopy and flow cytometry, while
      caspase 3/7 activity was detected using FLICA caspase inhibitor and analysed by
      fluorescence microscopy. RESULTS: Selected sub-fractions of the dichloromethane
      extract induced death of MCF-7, MDA-MB-231, PC-3 and DU-145 cells. The sub
      fraction SC/D-F9, consistently killed breast and prostate cancer cell lines with
      low EC50 values but is non-cytotoxic to the normal breast epithelial cell line,
      MCF-10A. SC/D-F9 displayed relatively higher cytotoxicity compared to tamoxifen,
      paclitaxel, docetaxel and doxorubicin. Cell death induced by SC/D-F9 occurred via
      apoptosis with the involvement of caspase 3 and/or 7. CONCLUSIONS: A
      dichloromethane sub-fraction of S. crispus displayed potent anticancer activities
      in vitro that can be further exploited for the development of a potential
      therapeutic anticancer agent.

PMID- 20684796
TI  - Predicting sequelae and death after bacterial meningitis in childhood: a
      systematic review of prognostic studies.
AB  - BACKGROUND: Bacterial meningitis (BM) is a severe infection responsible for high
      mortality and disabling sequelae. Early identification of patients at high risk
      of these outcomes is necessary to prevent their occurrence by adequate treatment
      as much as possible. For this reason, several prognostic models have been
      developed. The objective of this study is to summarize the evidence regarding
      prognostic factors predicting death or sequelae due to BM in children 0-18 years
      of age. METHODS: A search in MEDLINE and EMBASE was conducted to identify
      prognostic studies on risk factors for mortality and sequelae after BM in
      children. Selection of abstracts, full-text articles and assessment of
      methodological quality using the QUIPS checklist was performed by two reviewers
      independently. Data on prognostic factors per outcome were summarized. RESULTS:
      Of the 31 studies identified, 15 were of moderate to high quality. Due to
      substantial heterogeneity in study characteristics and evaluated prognostic
      factors, no quantitative analysis was performed. Prognostic factors found to be
      statistically significant in more than one study of moderate or high quality are:
      complaints > 48 hours before admission, coma/impaired consciousness, (prolonged
      duration of) seizures, (prolonged) fever, shock, peripheral circulatory failure,
      respiratory distress, absence of petechiae, causative pathogen Streptococcus
      pneumoniae, young age, male gender, several cerebrospinal fluid (CSF) parameters
      and white blood cell (WBC) count. CONCLUSIONS: Although several important
      prognostic factors for the prediction of mortality or sequelae after BM were
      identified, the inability to perform a pooled analysis makes the exact
      (independent) predictive value of these factors uncertain. This emphasizes the
      need for additional well-conducted prognostic studies.

PMID- 20684797
TI  - Antisecretory factor as a potential health-promoting molecule in man and animals.
AB  - Antisecretory factor (AF) is a protein secreted in plasma and other tissue fluids
      in mammals with proven antisecretory and anti-inflammatory activity; its
      immunohistological distribution suggests a role in the immune system. The
      expression level and the distribution of AF protein are altered during an
      immunological response. Exposure to bacterial toxins induces secretion of AF in
      plasma, probably reflecting a natural defence mechanism to agents causing
      diarrhoea, thereby contributing to a favourable clinical outcome and disease
      termination. An increase of AF levels in plasma by dietary means, such as
      specially processed cereals (SPC), has been demonstrated in human subjects and
      animals. Administration of SPC to patients affected by inflammatory bowel
      disease, gastroenteritis and Meniere's disease relieved symptoms and improved
      quality of life. A recent study showed the positive effect of SPC diet
      supplementation on prevention of the effects of exposure to low levels of blast
      overpressure in rats, reducing the extent of intracranial pressure increase and
      cognitive function impairment. AF-rich egg yolk powder improved health status in
      children suffering acute and chronic diarrhoea, reducing the frequency and
      increasing the consistency of stools. This kind of functional food could be used
      for prophylaxis in populations exposed to a high risk of morbidity and mortality
      caused by diarrhoea and as a complementary therapy in patients affected by
      chronic intestinal inflammatory disease to improve well-being. In pig husbandry
      AF-inducing diets, owing to their antisecretory activity and anti-inflammatory
      action, are a suitable option as an alternative to antibiotic growth promoters to
      counteract post-weaning diarrhoea.

PMID- 20684799
TI  - On the suitability of SIFT technique to deal with image modifications specific to
      confocal scanning laser microscopy.
AB  - Computer vision tasks such as recognition and classification of objects and
      structures or image registration and retrieval can provide significant
      information when applied to microscopy images. Recently developed techniques for
      the detection and description of local features make the extraction and
      description of local image features that are invariant to various changes
      possible. The invariance and robustness of feature detection and description
      techniques play a key role in the design and implementation of object
      recognition, image registration, or image mosaicing applications. The scale
      invariant feature transform (SIFT) technique is a widely used method for the
      detection, description, and matching of image features. In this article we
      present the results of our experiments regarding the repeatability of SIFT
      features, and to the precision of the SIFT feature matching, under image
      modifications specific to confocal scanning laser microscopy (CSLM). We have
      analyzed the behavior of SIFT while changing the pinhole aperture,
      photomultiplier gain, laser beam power, and electronic zoom. Our experiments,
      conducted on CSLM images, show that the SIFT technique is able to match detected
      key points between images acquired at different values of the acquisition
      parameters with good precision and represents a consistent tool for computer
      vision applications in CSLM.

PMID- 20684800
TI  - Measurement of oxygen diffusivity and permeability in polymers using fluorescence
      microscopy.
AB  - A simple fluorescence microscopy technique is developed and presented to
      investigate heterogeneities in emission intensity and quenching responses of
      luminescence sensors and to measure diffusion and permeation coefficients of
      oxygen in polymers. Most luminescence oxygen sensors do not follow linearity of
      the Stern-Volmer (SV) equation due to heterogeneity of luminophore in the polymer
      matrix. To circumvent this limitation, inverted fluorescence microscopy is
      utilized in this work to investigate the SV response of the sensors at the micron
      scale. It was found that intensity is higher in regions where the luminophore is
      aggregated, but the response is poorer to oxygen concentration. In contrast, the
      nearly homogeneous regions exhibit linearity with high SV constants. In these
      diffusion experiments, oxygen concentration was measured by luminescence changes
      in regions with high SV constants and good linearity. Two diffusion experiments
      were performed-termed film-on-sensor and accumulation-in-volume techniques. A new
      Fick's law based quasi-steady-state diffusion model was developed and combined
      with the SV equation to obtain effective permeation coefficients for the
      accumulation-in-volume technique. Using these experimental techniques, oxygen
      diffusion properties in free-standing Teflon polymer films, cast silicon
      elastomers, and cast polydimethylsiloxane films containing different weight
      percentages of zeolite were determined with good precision.

PMID- 20684798
TI  - Multiphoton flow cytometry to assess intrinsic and extrinsic fluorescence in
      cellular aggregates: applications to stem cells.
AB  - Detection and tracking of stem cell state are difficult due to insufficient means
      for rapidly screening cell state in a noninvasive manner. This challenge is
      compounded when stem cells are cultured in aggregates or three-dimensional (3D)
      constructs because living cells in this form are difficult to analyze without
      disrupting cellular contacts. Multiphoton laser scanning microscopy is uniquely
      suited to analyze 3D structures due to the broad tunability of excitation
      sources, deep sectioning capacity, and minimal phototoxicity but is throughput
      limited. A novel multiphoton fluorescence excitation flow cytometry (MPFC)
      instrument could be used to accurately probe cells in the interior of multicell
      aggregates or tissue constructs in an enhanced-throughput manner and measure
      corresponding fluorescent properties. By exciting endogenous fluorophores as
      intrinsic biomarkers or exciting extrinsic reporter molecules, the properties of
      cells in aggregates can be understood while the viable cellular aggregates are
      maintained. Here we introduce a first generation MPFC system and show appropriate
      speed and accuracy of image capture and measured fluorescence intensity,
      including intrinsic fluorescence intensity. Thus, this novel instrument enables
      rapid characterization of stem cells and corresponding aggregates in a
      noninvasive manner and could dramatically transform how stem cells are studied in
      the laboratory and utilized in the clinic.

PMID- 20684801
TI  - Foreword.

PMID- 20684802
TI  - Editorial. Should a neuroradiologist be a clinician?

PMID- 20684804
TI  - Education of interventional neuroradiologists.

PMID- 20684803
TI  - Presentation.

PMID- 20684805
TI  - Early Clinical Outcome of Patients with Ruptured Cerebral Aneurysms Treated by
      Endovascular (GDC) or Microsurgical Techniques. A Single Center Experience.
AB  - SUMMARY: Over the past 3.5 years 220 patients with aneurysmal subarachnoid
      hemorrhage were treated in the Department of Neurosurgery University of Vienna
      Medical School using either endovascular techniques (Guglielmi Detachable Coils)
      or open craniotomy with aneurysm clipping. A retrospective analysis was
      undertaken to assess whether any difference in outcome could be correlated with
      the treatment choice. The patients were stratified as to 1) Hunt and Hess grade
      at time of treatment, 2) method of treatment, and 3) clinical outcome at 2-4
      weeks following treatment. The outcomes in this population of patients were
      consistent with recent published series regardless of whether the aneurysms were
      treated with microvascular surgery or endovascular surgery. There was a trend
      toward better outcome in a relatively small sub-group of patients presenting as
      Hunt and Hess grade III who were treated by the endovascular method. Guglielmi
      detachable coils have been available for a relatively short time, and although
      early results are promising, the ultimate long-term efficacy of the coils will
      have to be assessed.

PMID- 20684806
TI  - Spinal Cord Arteriovenous Malformations in a Pediatric Population Children below
      15 Years of Age The Place of Endovascular Management.
AB  - SUMMARY: Among a global group of 164 spinal arteriovenous shunts, a series of 16
      spinal cord arteriovenous malformations (SCAVMs) were diagnosed in a pediatric
      population below 15 years of age. The majority of the lesions affected the male
      population; 6 were located in the cervical spine and 10 at the thoracolumbar
      level. Hemorrhage was the most frequent symptom encountered (63%). Half of the
      bleeds occurred only in the subarachnoid spaces. Neurological deficits (acute or
      progressive) revealed the SCAVM in 31 % of patients. The lesion was an incidental
      finding in one patient (6%). All the diagnoses (except one) were made by MRI.
      Selective angiography confirmed the diagnosis and identified the type of the
      lesion (nidus or fistula) and its angioarchitecture, stressing that the veins and
      their related features are the key point in the clinical eloquence of SCAVMs. All
      the treatments performed were endovascular; no patient was deemed a surgical
      candidate. Therapeutic abstention was decided in 37% of cases, mainly for
      anatomical reasons. All the patients in this group improved (50% being normal and
      50% presenting slight non-handicapping deficits due to the initial accidents).
      Embolisation was indicated in 10 patients (63%) and was performed with fluid
      agents (histoacryl(*)) except in the first patient who had been treated with
      particles. Twelve percent of patients were cured (fistula), the remaining 88%
      having their lesion controlled to more than 50%. This partial treatment was
      always targetted towards the angioarchitectural weak points of the lesion. All
      patients improved after embolisation, 45% of them being neurologically normal.
      Follow-up in this group ranges from 1.5 to 13 Years. No complications occurred
      after embolisation. No bleed, rebleed or clinical worsening has occurred after
      endovascular treatment. The results in this series suggest that endovascular
      treatment (even partial but targetted) represents a safe and stable therapeutic
      alternative in the management of SCAVMs in this population.

PMID- 20684807
TI  - Angio-CT. A Proposal for Emergency Diagnosis in Subarachnoid Hemorrhage as a
      Preliminary to Therapeutic Choices.
AB  - SUMMARY: After nine months' experience with helical CT (Elscint Twin), we
      describe an epicrisis in 13 patients with intracranial aneurysms, 12 of whom were
      referred to us by the emergency room for suspect subarachnoid hemorrhage. After
      standard CT scan confirming subarachnoid hemorrhage, patients underwent angio-CT
      with display of the sac responsible for bleeding in all cases. All patients
      subsequently underwent digital angiography which confirmed the angio-CT findings
      and in three cases disclosed associated malformations. The sensitivity,
      specificity and diagnostic accuracy of the technique are assessed in relation to
      the quality of the images obtained (MIP) in such a short time (15 min on
      average). The diagnostic information is comparable to that offered by angio-MR
      with the obvious positive and negative aspects linked to each method. Digital
      angiography remains the technique of choice in terms of diagnostic accuracy, but
      carries some risk to the patient.

PMID- 20684808
TI  - Role of 3D Display MR Angiography in the Study of Intracranial Aneurysms.
AB  - SUMMARY: This paper determines the usefulness of threedimensional (3D) phase
      contrast (PC) magnetic resonance (MR) angiography with 3D display in
      characterizing large intracranial saccular aneurysms. Eight patients referred for
      non invasive confirmation of unruptured aneurysm (n=9) detected by conventional
      CT and/or MR imaging were studied by 3D PC (VENC of 20 cm/s, 3 axes) in axial
      acquisition localised on the circle of Willis using a 0.5 T unit (Vectra, GE). We
      used 3D display images to assess the feasibility of selective treatment. Results
      were correlated with catheter angiograms in 3 patients. In two thirds of the
      cases, location and size of the orifice, size of the sac, and clarification of
      parent artery were clearly provided allowing prediction of therapeutic
      management. In the remaining cases results remained doubful because of lack of
      spatial resolution. The benefit of the method was coupled with the clinical
      status of the patients to influence the final decision. 3D PC MR angiography with
      3D display has emerged as an improvement in predicting therapeutic management,
      and is especially useful in large unruptured aneurysms in elderly or ill
      patients.

PMID- 20684809
TI  - Intensive care management of patients with subarachnoid hemorrhage at san
      raffaele hospital, milan.
AB  - SUMMARY: Intensive care of patients with SAH is targeted to recognize and treat
      the leading cause of death and disability. Hemorrhage, vasospasm, rebleeding,
      intracranial hypertension can produce ischaemia because the ratio between
      metabolism (CMR0 (2) ) and cerebral blood flow (CBP) is not coupled. Neuro-ICU
      bedside monitoring provides information on the intracranial dynamics. Aggressive
      treatment attempts to avoid ischaemia but needs a clipped or thrombosed (via
      endovascular approach) aneurysm. The authors propose treatment to improve CBP and
      reduce CMRO (2) : hypervolaemia, hemodilution, hypertension, ICP reduction,
      normocapnia, mannitol infusion, normothermia or mild hypothermia and sedation
      with intravenous anaesthetics. Medical complications such as hypovolemia,
      infections, pulmonary oedema, gastrointestinal bleeding need to be recognized
      early and treated.

PMID- 20684810
TI  - Towards single embryo transfer? Modelling clinical outcomes of potential
      treatment choices using multiple data sources: predictive models and patient
      perspectives.
AB  - BACKGROUND: In vitro fertilisation (IVF) treatments involve an egg retrieval
      process, fertilisation and culture of the resultant embryos in the laboratory,
      and the transfer of embryos back to the mother over one or more transfer cycles.
      The first transfer is usually of fresh embryos and the remainder may be
      cryopreserved for future frozen cycles. Most commonly in UK practice two embryos
      are transferred (double embryo transfer, DET). IVF techniques have led to an
      increase in the number of multiple births, carrying an increased risk of maternal
      and infant morbidity. The UK Human Fertilisation and Embryology Authority (HFEA)
      has adopted a multiple birth minimisation strategy. One way of achieving this
      would be by increased use of single embryo transfer (SET). OBJECTIVES: To collate
      cohort data from treatment centres and the HFEA; to develop predictive models for
      live birth and twinning probabilities from fresh and frozen embryo transfers and
      predict outcomes from treatment scenarios; to understand patients' perspectives
      and use the modelling results to investigate the acceptability of twin reduction
      policies. METHODS: A multidisciplinary approach was adopted, combining
      statistical modelling with qualitative exploration of patients' perspectives:
      interviews were conducted with 27 couples at various stages of IVF treatment at
      both UK NHS and private clinics; datasets were collated of over 90,000 patients
      from the HFEA registry and nearly 9000 patients from five clinics, both over the
      period 2000-5; models were developed to determine live birth and twin outcomes
      and predict the outcomes of policies for selecting patients for SET or DET in the
      fresh cycle following egg retrieval and fertilisation, and the predictions were
      used in simulations of treatments; two focus groups were convened, one NHS and
      one web based on a patient organisation's website, to present the results of the
      statistical analyses and explore potential treatment policies. RESULTS: The
      statistical analysis revealed no characteristics that specifically predicted
      multiple birth outcomes beyond those that predicted treatment success. In the
      fresh transfer following egg retrieval, SET would lead to a reduction of
      approximately one-third in the live birth probability compared with DET, a result
      consistent with the limited data from clinical trials. From the population or
      clinic perspective, selection of patients based on prognostic indicators might
      mitigate about half of the loss in live births associated with SET in the initial
      fresh transfer while achieving a twin rate of 10% or less. Data-based simulations
      suggested that, if all good-quality embryos are replaced over multiple frozen
      embryo transfers, repeated SET has the potential to produce more live birth
      events than repeated DET. However, this would depend on optimising
      cryopreservation procedures. Universal SET could both reduce the number of twin
      births and lead to more couples having a child, but at an average cost of one
      more embryo transfer procedure per egg retrieval. The interview and focus group
      data suggest that, despite the potential to maintain overall success rates,
      patients would prefer DET: the potential for twins was seen as positive, while
      additional transfer procedures can be emotionally, physically and financially
      draining. CONCLUSIONS: For any one transfer, SET has about a one-third loss of
      success rate relative to DET. This can be only partially mitigated by patient and
      treatment cycle selection, which may be criticised as unfair as all patients
      receiving SET will have a lower chance of success than they would with DET.
      However, considering complete cycles (fresh plus frozen transfers), it is
      possible for repeat SET to produce more live births than repeat DET. Such a
      strategy would require support from funders and acceptance by patients of both
      cryopreservation and the burden of additional transfer cycles. Future work should
      include development of improved clinical and regulatory database systems, surveys
      to quantify the extent of patients' beliefs and experiences and develop
      approaches to meet their information needs, and, ideally, randomised controlled
      trials comparing policies of repeated SET with repeated DET.

PMID- 20684812
TI  - Meteorological and climate change themes at the 2010 International Conference on
      Emerging Infectious Diseases.

PMID- 20684813
TI  - Seroprevalence of brucellosis in animals and human populations in the western
      mountains region in Libya, December 2006-January 2008.
AB  - Brucellosis is a global zoonotic disease, endemic in North African countries and
      around the Mediterranean.A prospective study of Brucella seroprevalence was
      conducted in north-western Libya (western mountains region). Blood samples
      collected over 13 months in the period December 2006 to January 2008 from 561
      animals (goats, sheep, cattle and camels) and 546 human volunteers were tested
      for Brucella using the Rose Bengal test, tube agglutination test and ELISA
      assays. Amongst livestock, 31% of goats and 42% of cattle were seropositive.
      Human samples showed a high seropositivity of 40%, with 95 (43%) of the 221
      positive samples positive for IgM, indicating active or recent infection. Control
      measures are needed to reduce this high prevalence of brucellosis in Libya.

PMID- 20684814
TI  - Regional and age-specific patterns of pandemic H1N1 influenza virus
      seroprevalence inferred from vaccine clinical trials, August-October 2009.
AB  - The extent of the H1N1 pandemic has been estimated from case counts and deaths
      but the proportion of exposed populations with inapparent infections has not been
      described in detail. We analysed haemagglutination-inhibition (HI) antibody
      titres of pre-vaccination sera from pandemic vaccine trials conducted in six
      countries on four continents to provide an indication of A/CA/07/2009(H1N1)-like
      influenza seroprevalence in those populations. Among 7,962 subjects, ranging in
      age from 12 months to over 60 years, the proportions with HI antibody titres > or
      =40 to the H1N1pnd virus in the period from August to October 2009 were, by
      country: Costa Rica 26.4%, United States (US) 22.5%, Switzerland 16.9%, Germany
      12.6%, Belgium 10.1%, and Japan 5.9%. Age-specific seropositivity rates in the
      samples were higher in children and adolescents in Costa Rica and in the US than
      in Europe and in Japan. The low proportion of seropositive children in Europe and
      Japan suggests that little local viral transmission had occurred in those regions
      even as late as September and October 2009, while in the US and Costa Rica, the
      greater proportion of previously infected children and young adults suggested
      that a significant number of asymptomatic infections had occurred during the
      first pandemic wave. Nevertheless, in all locations, the majority of the
      population remained susceptible to the pandemic virus at the beginning of the
      influenza season in the northern hemisphere, justifying the implementation of
      public health interventions.

PMID- 20684815
TI  - Event-based biosurveillance of respiratory disease in Mexico, 2007-2009:
      connection to the 2009 influenza A(H1N1) pandemic?
AB  - The emergence of the 2009 pandemic influenza A(H1N1) virus in North America and
      its subsequent global spread highlights the public health need for early warning
      of infectious disease outbreaks. Event-based biosurveillance, based on local- and
      regional-level Internet media reports, is one approach to early warning as well
      as to situational awareness. This study analyses media reports in Mexico
      collected by the Argus biosurveillance system between 1 October 2007 and 31 May
      2009. Results from Mexico are compared with the United States and Canadian media
      reports obtained from the HealthMap system. A significant increase in reporting
      frequency of respiratory disease in Mexico during the 2008-9 influenza season
      relative to that of 2007-8 was observed (p<0.0001). The timing of events, based
      on media reports, suggests that respiratory disease was prevalent in parts of
      Mexico, and was reported as unusual, much earlier than the microbiological
      identification of the pandemic virus. Such observations suggest that abnormal
      respiratory disease frequency and severity was occurring in Mexico throughout the
      winter of 2008-2009, though its connection to the emergence of the 2009 pandemic
      influenza A(H1N1) virus remains unclear.

PMID- 20684816
TI  - Spotlight on measles 2010: ongoing measles outbreak in Greece, January-July 2010.
AB  - A measles outbreak (126 reported cases to date) has been ongoing in Greece, since
      January 2010, originally related to the recent outbreak in Bulgaria. Cases are
      mostly unvaccinated, and mainly belong to three groups: Roma population of
      Bulgarian nationality, Greek Roma population, and Greek non-minority population.
      In these population groups, 67%, 95%, and 25% of cases respectively were children
      aged 0-14 years. Measures were taken to raise clinical awareness, and vaccination
      of specific population groups was undertaken. Policies are necessary to increase
      routine vaccination uptake of hard-to-reach groups.

PMID- 20684821
TI  - [Enlarged vestibular aqueduct syndrome. A review of 55 paediatric patients].
AB  - INTRODUCTION: Enlarged vestibular aqueduct (EVA) is the commonest congenital
      anomaly found with imaging techniques in paediatric sensorineural hearing loss
      (SNHL). Our aim was to describe clinical and audiological findings in paediatric
      hearing loss associated to EVA. METHODS: Retrospective review of 55 children with
      imaging-technique EVA findings from 2000 to 2009. Subjective and/or objective
      audiological tests were analysed and audiological findings related to clinical
      features were described. RESULTS: Thirty-seven patients (67.27%) showed bilateral
      EVA and 18 (32.72%) were unilateral. Hearing loss was bilateral in 46 (83.63%)
      patients and unilateral in 9 (16.36%). Mean age at diagnosis was 3.78 years.
      Fifty-three (96.36%) children showed SNHL (28 bilateral and profound), while 2
      (3.63%) patients had mixed hearing loss. There were 3 cases of hearing loss
      progression, 2 fluctuations, 2 of them were asymmetric and 2 patients suffered
      from vestibular symptoms. Concomitant image findings were 6 cochlear hypoplasia,
      2 enlarged internal auditory canals, 1 enlarged vestibule and 1 hypoplastic
      lateral semicircular canal. Six clinical syndromes were found (2 cases of Down's,
      and 1 each of Jacobsen, Pendred, Waardenburg and branchio-oto-renal). One child
      was positive for GJB2 mutation. Familial hearing loss was demonstrated on 12
      (21.8%) cases. CONCLUSION: The clinical picture of hearing loss associated to EVA
      is characterised by great variability. It should be included in the differential
      diagnosis of unexplained mixed hearing loss. Familial and syndromic findings have
      to be taken into consideration in the diagnostic evaluations of such patients.
      Knowledge about the natural history of this illness is needed so as to give
      parents prognostic information.

PMID- 20684822
TI  - [Oncologic and functional results of surgical treatment for base of tongue
      carcinomas].
AB  - INTRODUCTION AND OBJECTIVES: Squamous cell carcinomas at the base of the tongue
      are usually diagnosed at advanced stages, and their optimal treatment has not
      been established. The aim of this study was to describe the functional and
      oncological outcomes of patients with base of tongue carcinomas treated with
      surgery. MATERIALS AND METHODS: A retrospective study on 132 patients with base
      of tongue carcinoma surgically treated in our hospital between 1990 and 2007 was
      carried out. One patient (0.75%) was in stage I, 8 (6%) were in stage II, 15
      (11%) in stage III, 91 (69%) in stage IVA, and 17 (13%) with stage IVB. A total
      of 92 (70%) patients received postoperative radiotherapy. RESULTS: Eighty-seven
      patients (66%) had recurrence: 23 patients (17%) had local recurrence, 15 (11%)
      regional, 20 (15%) locoregional, 16 (12%) locoregional and distant, and 9 (7%)
      distant metastases. The disease-specific survival was 34% at 5 years (100% for
      stages I and II, 44% for stage III, 28% for stage IVA and 12% for IVB; p=0.0004).
      Multivariate analysis showed two variables independently associated with worse
      survival: lymph node metastases classified as N2-3 (p=0.016) and primary tumours
      classified as T3-4 (p=0.040). Adequate oral intake was achieved by 96% of the
      patients and 79% could be decannulated. CONCLUSIONS: The prognosis of squamous
      cell carcinomas of the base of the tongue is poor, especially in advanced stages.
      Surgical treatment provides oncological and functional results similar to other
      therapeutic modalities.

PMID- 20684824
TI  - Association of monocyte subsets with vulnerability characteristics of coronary
      plaques as assessed by 64-slice multidetector computed tomography in patients
      with stable angina pectoris.
AB  - OBJECTIVE: The aim of the present study was to examine the relation between
      monocyte subsets and the presence, extent, and vulnerability characteristics of
      non-calcified coronary plaques (NCPs) as assessed by multidetector computed
      tomography (MDCT). METHODS: We studied 73 patients with stable angina pectoris
      who underwent MDCT. Two monocyte subsets (CD14(+)CD16(-) and CD14(+)CD16(+)) were
      measured by flow cytometry. Coronary artery plaques were assessed by 64-slice
      MDCT. We defined NCP vulnerability according to the presence of positive
      remodeling (remodeling index>1.05) and/or low CT attenuation plaques (<35 HU).
      RESULTS: A total of 40 (55%) patients had identifiable vulnerable plaques. The
      relative proportion of CD14(+)CD16(+) monocytes was significantly greater in
      patients with 1 or multiple vulnerable plaques than in patients with no
      vulnerable plaques or control (healthy) subjects. In addition, the relative
      proportion of CD14(+)CD16(+) monocytes was positively correlated with remodeling
      index (r=0.40, P<0.01) and negatively correlated with CT attenuation value (r=
      0.34, P<0.01). CONCLUSION: The present results suggest that an increased subset
      of CD14(+)CD16(+) monocytes is related to coronary plaque vulnerability in
      patients with stable angina pectoris.

PMID- 20684825
TI  - Correlation between circulating adiponectin levels and coronary plaque regression
      during aggressive lipid-lowering therapy in patients with acute coronary
      syndrome: subgroup analysis of JAPAN-ACS study.
AB  - OBJECTIVE: The Japan assessment of pitavastatin and atorvastatin in acute
      coronary syndrome (JAPAN-ACS) study demonstrated that aggressive lipid-lowering
      therapy with a statin resulted in a significant regression of coronary
      atherosclerotic plaques in patients with ACS. Adiponectin is an adipocyte-derived
      protein with anti-atherogenic properties. Here, we investigated the association
      between adiponectin levels and the change in the plaque volume in ACS patients.
      METHODS: Intravascular ultrasound (IVUS)-guided percutaneous coronary
      intervention (PCI) was undertaken, followed by the initiation of statin
      treatment, in 238 patients with ACS. Follow-up IVUS was performed between 8 and
      12 months after the PCI. The percent change in the plaque volume (%PV) in a non
      culprit coronary artery segment was evaluated. The serum adiponectin and lipid
      parameters were measured both at baseline and at the follow-up. RESULTS: At
      baseline, adiponectin was correlated positively with HDL-cholesterol and
      negatively correlated with triglyceride, but no correlation was observed with the
      PV. Adiponectin levels increased significantly from 7.8+/-4.6 microg/mL at
      baseline to 10.3+/-6.9 microg/mL at the 8-12 months follow-up. The increase in
      adiponectin was also associated with an increase of HDL-cholesterol and decrease
      of triglyceride, however, no significant correlation was observed with the %PV. A
      significantly higher incidence of major adverse cardiac events (MACE) was
      observed in patients with hypo-adiponectinemia at baseline. A multiple logistic
      regression analysis identified adiponectin as a significant independent predictor
      of MACE. CONCLUSION: Adiponectin levels measured after PCI could serve as a
      marker of MACE in patients with ACS.

PMID- 20684826
TI  - Chronic infusion of salusin-alpha and -beta exerts opposite effects on
      atherosclerotic lesion development in apolipoprotein E-deficient mice.
AB  - OBJECTIVE: Human salusin-alpha and -beta are two-related peptides processed from
      the same precursor, preprosalusin. Our previous in vitro studies have shown that
      human macrophage foam cell formation is stimulated by salusin-beta but suppressed
      by salusin-alpha. Thus we investigated the effects of salusin-alpha and -beta on
      atherosclerotic plaque formation in vivo in apolipoprotein E-deficient (ApoE-/-)
      mice. METHODS: Saline (vehicle), salusin-alpha or -beta (0.6 nmol/kg/h) was
      continuously infused through osmotic mini-pumps into 13-week-old ApoE-/- mice for
      8 weeks. Aortic atherosclerosis, oxidized LDL-induced cholesterol ester
      accumulation (foam cell formation), and its related gene expression in exudate
      peritoneal macrophages were determined. RESULTS: After 4-week infusion of salusin
      beta, atherosclerotic lesions were 2.6 times greater than vehicle controls, which
      paralleled 1.9-fold increase in foam cell formation and up-regulation of
      scavenger receptors (CD36, scavenger receptor class A) and acyl-CoA: cholesterol
      acyltransferase-1 (ACAT1). In contrast, salusin-alpha decreased serum total
      cholesterol levels by 15% and foam cell formation by 68% associated with ACAT1
      down-regulation. After 8-week infusion of salusin-alpha, atherosclerotic lesions
      were significantly suppressed by 54% compared with vehicle controls. CONCLUSIONS:
      Our study provided the first evidence that salusin-beta accelerates the
      development of atherosclerotic lesions associated with up-regulation of scavenger
      receptors and ACAT1 in ApoE-/- mice. Whilst, salusin-alpha exerts anti
      atherosclerotic effects by suppressing serum total cholesterol levels and ACAT1
      expression.

PMID- 20684827
TI  - Anti-atherogenic effect of BHB-TZD having inhibitory activities on cyclooxygenase
      and 5-lipoxygenase in hyperlipidemic mice.
AB  - Cyclooxygenase (COX) and 5-lipoxygenase (5-LOX), which play pivotal roles in
      atherogenesis, have been reported to be involved in plaque stability. Licofelone,
      a dual COX and 5-LOX inhibitor, has been reported to possess anti-atherogenic
      effect in rabbit atherosclerosis model. We therefore investigated the anti
      atherogenic effect of BHB-TZD [5-(3,5-di-tert-butyl-4
      hydroxybenzylidene)thiazolidin-2,4-dione], a dual COX and 5-LOX inhibitor, in low
      density lipoprotein receptor null (LDLR-/-) mice. Fifteen LDLR-/- mice were fed a
      western diet (control group), whereas 15 were fed a western diet plus 0.1% (w/w)
      BHB-TZD (BHB-TZD group). After 8 weeks, the BHB-TZD group had markedly lower
      serum levels of leukotriene B(4) and prostaglandin E(2) than the control group.
      Interestingly, BHB-TZD treatment also reduced plasma triglyceride level without
      significant changes in total cholesterol and HDL levels. Compared with control
      mice, BHB-TZD fed mice had 52% fewer fatty streak lesions in the aortic sinus, as
      well as fewer initial lesions in the aortic arch. Macrophage infiltration into
      the lesions was 40% lower, and collagen and smooth muscle cells were increased by
      102% and 96%, respectively, in the BHB-TZD group compared with the control group.
      In addition, aortic expression of proatherogenic molecules including TNF-alpha,
      IL-1beta, IL-6, MCP-1 and VCAM-1, was lower in the BHB-TZD group than the control
      group. BHB-TZD treatment also reduced MMP-2 and MMP-9 expressions in aorta. In
      conclusion, BHB-TZD effectively attenuated atherosclerosis in mouse model,
      suggesting its therapeutic potential for atherosclerosis.

PMID- 20684831
TI  - Possible association of the semaphorin 3D gene (SEMA3D) with schizophrenia.
AB  - Semaphorins are ligands of plexins, and the plexin-semaphorin signaling system is
      widely involved in many neuronal events including axon guidance, cell migration,
      axon pruning, and synaptic plasticity. The plexin A2 gene (PLXNA2) has been
      reported to be associated with schizophrenia. This finding prompted us to examine
      the possible association between the semaphorin 3D gene (SEMA3D) and
      schizophrenia in a Japanese population. We genotyped 9 tagging single nucleotide
      polymorphisms (SNPs) of SEMA3D including a non-synonymous variation, Lys701Gln
      (rs7800072), in a sample of 506 patients with schizophrenia and 941 healthy
      control subjects. The Gln701 allele showed a significant protective effect
      against the development of schizophrenia (p = 0.0069, odds ratio = 0.76, 95%
      confidence interval 0.63 to 0.93). Furthermore, the haplotype-based analyses
      revealed a significant association. The four-marker analysis (rs2190208-rs1029564
      rs17159614-rs12176601), in particular, not including the Lys701Gln, revealed a
      highly significant association (p = 0.00001, global permutation), suggesting that
      there may be other functional polymorphisms within SEMA3D. Our findings provide
      strong evidence that SEMA3D confers susceptibility to schizophrenia, which could
      contribute to the neurodevelopmental impairments in the disorder.

PMID- 20684828
TI  - Specific binding of hypochlorite-oxidized HDL to platelet CD36 triggers
      proinflammatory and procoagulant effects.
AB  - OBJECTIVE: Oxidative stress and systemic inflammation negatively affect several
      protective functions of high density lipoproteins (HDL) and oxidative
      modification of HDL by the inflammation-derived oxidant hypochlorite converts HDL
      into a potent platelet agonist. Therefore it was the aim of this work to clarify
      if these platelet-activating effects result from specific binding of hypochlorite
      oxidized HDL (hyp-OxHDL) to the platelet surface and to identify responsible
      receptors. METHODS: Binding and functional studies were performed with hyp-OxHDL
      in absence and presence of (potential) competitors in normal and CD36-deficient
      human platelets. Platelet aggregation was quantified by light transmission
      aggregometry. Surface expression of CD62P, phosphatidylserine and CD40L was
      quantified by flow cytometry. RESULTS: Binding studies reveal that hyp-OxHDL show
      specific and saturable high-affinity binding to the platelet surface. Hyp-OxHDL
      trigger platelet aggregation and in a dose dependent way provoke the release of
      significant amounts of CD40L as well as phosphatidylserine on the platelet
      surface. Blocking specific binding of hyp-OxHDL to the platelet surface
      interferes with the ability of hyp-OxHDL to stimulate human platelets. CD36
      deficient human platelets show markedly reduced binding of hyp-OxHDL. Upon
      addition of hypochlorite-oxidized HDL, CD36-deficient platelets do not aggregate
      and completely fail to release CD40L or phosphatidylserine. CONCLUSIONS: From
      these results we conclude that specific binding of hyp-OxHDL to platelet CD36 is
      essential for the proinflammatory and procoagulant effects of hyp-OxHDL shown
      within this work. The contribution of other receptors besides CD36 to specific
      binding of hyp-OxHDL to the platelet membrane appears to be minimal, at best.

PMID- 20684832
TI  - Differential regional N-acetylaspartate deficits in postmortem brain in
      schizophrenia, bipolar disorder and major depressive disorder.
AB  - There is substantial evidence for the involvement of the hippocampus and
      subcortical regions in the neuropathology of schizophrenia. Deficits of N
      acetylaspartate (NAA) have been found in schizophrenia and bipolar disorder which
      may reflect neuronal loss and/or dysfunction. N-acetylaspartylglutamate (NAAG) is
      the most abundant peptide transmitter in the mammalian nervous system. It is an
      agonist at presynaptic metabotropic glutamate receptors mGluR3, inhibiting
      glutamate release. NAA and NAAG and were measured in hippocampal, striatal,
      amygdala and cingulate gyrus regions of human postmortem tissue from controls and
      subjects with schizophrenia, bipolar disorder and major depressive disorder.
      There are significant deficits in hippocampal NAA concentrations in all patient
      groups. In the amygdala there are significant NAA deficits in schizophrenia and
      depression and significant deficits of NAAG in the amygdala in the depression
      group. The deficits in NAA reported in this study confirm the importance of
      hippocampal and other subcortical structures in the neuropathology of the major
      psychiatric disorders.

PMID- 20684833
TI  - Social fear and social phobia types among community youth: differential clinical
      features and vulnerability factors.
AB  - OBJECTIVE: To compare different social fears and social phobia subtypes with
      regard to clinical (age of onset, avoidance, impairment, comorbidities) and
      vulnerability factors (behavioural inhibition (BI), parental psychopathology and
      parental rearing) among community youth. METHODS: Fears of 6 social situations
      and Social Phobia (SP), along with their clinical features, were assessed using
      the Munich-Composite International Diagnostic Interview (DIA-X/M-CIDI) in a
      population-based sample of N = 3021 14-24 year olds that were followed up for 10
      years. BI and parental rearing were assessed using self-report questionnaires.
      Parental psychopathology was assessed directly in parents via DIA-X/M-CIDI,
      supplemented by offsprings' family history reports. RESULTS: In the total sample,
      20.0%, 11.6%, 11.7% reported fear of 1, 2, 3 or more social situations,
      respectively; rates were 24.2%, 18.7%, and 57.1% in SP-cases (6.6% of the total
      sample). Exploring the factorial structure indicated rather unidimensionality of
      social fears than mutual distinction of social fears by interaction vs.
      performance situations. Except for fear of taking tests and public speaking,
      social fears rarely occurred in isolation. Social fears of both interaction and
      performance situations were associated with severe avoidance (vs. fear of either
      situation; Odds Ratios, OR = 1.5, 95%CI: 1.1-1.9) and impairment (OR = 3.6,
      95%CI: 2.6-4.9), and more comorbid anxiety and depressive disorders (OR range 3.2
      5.8, p > .001). Fear of interaction situations was associated with higher BI (vs.
      performance-related fears, OR range 1.2-2.1, p < .05). Associations with parental
      psychopathology and unfavourable parental rearing were less consistent, albeit
      stronger for fear of interaction situations (vs. performance-related fears).
      Interactions with time indicated an earlier onset of SP for higher BI, but not
      for parental psychopathology or unfavourable parental rearing. CONCLUSIONS:
      Interaction-related social fears differ in their clinical and vulnerability
      factors from performance-related social fears. The current DSM-IV specifier of
      "generalized" SP may fall short of adequately denoting these differences. Fear of
      taking tests appears to be conceptually and, possibly, etiologically distinct
      from other social fears, and may be better placed in another category (e.g., as a
      type of specific phobia).

PMID- 20684835
TI  - Sperm morphology of the Prorops nasuta (Waterston, 1923) (Hymenoptera:
      Bethylidae).
AB  - In the present study, spermatozoa of the Prorops nasuta (Hymenoptera: Bethylidae)
      parasitoid were described morphologically. This is the first publication to
      describe a species belonging to the superfamily Chrysidoidea. Light and
      transmission electron microscopy were used. The spermatozoa of P. nasuta are
      linear, with a mean length of 665microm. The acrosome is composed of an acrosomal
      vesicle and a perforatorium. The nucleus measures approximately 17microm in
      length and is circular at its cross-section; however, its anterior extremity is
      oval. The chromatin is electron-dense and compact, although there are clear areas
      in the posterior peripheral regions. In the nucleus-flagellum transition region,
      the cross-section of the centriole adjunct is oval, with a pleated border and an
      E-PTA-positive peripheral region. The axoneme shows a 9+9+2 microtubule
      arrangement. The microtubules are E-PTA positive and, at the posterior extremity,
      the accessories are the last to terminate. The diameters and shapes of the two
      mitochondrial derivatives are almost identical. One begins beside the nuclear
      base and the other after the centriole adjunct. Posteriorly, they terminate
      together, immediately before the axoneme. Both have mitochondrial cristae and a
      region of paracrystalline material; however, the format and arrangement of this
      material differs from those of all other species previously studied. The
      paracrystalline material is more strongly E-PTA positive than the cristae region.
      Accessories bodies are electron-dense and located between the mitochondrial
      derivatives and the axoneme. In general, P. nasuta spermatozoa are similar to
      those of the majority of Hymenoptera; however, they have various exclusive
      characteristics that may be useful for studying the phylogeny and taxonomy of the
      superfamily Chrysidoidea and of Hymenoptera in general.

PMID- 20684836
TI  - Essence of keratin in lips and associated structures of a freshwater fish Puntius
      sophore in relation to its feeding ecology: histochemistry and scanning electron
      microscope investigation.
AB  - Morphological specializations in the lips and associated structures of Puntius
      sophore were examined by scanning electron microscopy and histochemically. The
      upper lip (UL), in P. sophore, is associated with the horny upper jaw sheath
      (HUJS) on its ventral side and with the rostral cap (RC) on its dorsal side
      through a thin and extensive fold of skin (FSUR). The lower lip (LL) is greatly
      enlarged, conspicuous and associated with horny lower jaw sheath (HLJS) on the
      dorsal side and ventrally continues with ventral head skin (VHS). On the lateral
      sides there is a thin and extensive fold of skin (FSLS) between the lower lip and
      VHS. In contrast to the mucogenic epithelia of the UL, LL, the RC and fold of
      skins, the horny jaw sheaths are keratinized in nature and surface epithelial
      cells are characteristically modified into unculi. The UL and the LL are equipped
      with epithelial cells (EC), mucous cells (MC) and taste buds (TB) while in
      addition to these cells club cells (CC) are also present in the RC. Keratin found
      in unculi is an extremely strong protein which is tough and insoluble, they form
      the hard but un-mineralized structures. Keratin in unculi could be regarded as an
      adaptation for browsing or scraping food materials from the substrate as the fish
      grubs about the bottom. The elaboration of mucus is considered to lubricate the
      surface and protect the epithelia from abrasions. Taste buds are associated to
      locate and select palatable food and to trigger a 'pick-up' reflex.

PMID- 20684843
TI  - Children's abilities to recognize a "good" person as a potential perpetrator of
      childhood sexual abuse.
AB  - OBJECTIVE: This study examined the ability of children to recognize "good" people
      as potential perpetrators prior to and after completing a personal safety
      program. There were three objectives to the study. The first was to determine
      whether young children could recognize the inappropriateness of a sexual request
      coming from people described as either "good" or "bad." Second, the study
      examined whether preschoolers could be educated to recognize inappropriate touch
      requests regardless of the good/bad descriptor. Finally, we explored if
      children's ability to learn the recognition skill depended upon their age.
      METHODS: Ninety-three, primarily Hispanic (72%) preschool children (M age=3.9
      years) completed the Body Safety Training program (BST; Wurtele, 2007), a
      classroom-based behavioral program. They responded to questions about "good" and
      "bad" people requesting to touch their private parts prior to and after the
      educational program. RESULTS: At pre-testing, children had more difficulty
      recognizing inappropriate touch requests when made by "good" people compared to
      "bad" people. After completing the BST program, children improved in their
      ability to recognize the inappropriateness of requests made by both "good" and
      "bad" people. At pretesting, correct responding varied across age groups, with a
      greater percentage of older children (age 5) correctly responding to the "bad"
      cases compared to 3- and 4-year olds. At post-testing, a marginally significant
      age difference was found for cases involving "good" people and significant
      differences were found for cases involving "bad" people. Almost all 4- and 5-year
      old children (94% and 96%, respectively) correctly responded to these
      inappropriate requests compared with only 71% of the 3 year olds. CONCLUSION: Pre
      test results demonstrated that young children had difficulty recognizing the
      inappropriateness of a request when it was made by a "good" person. Post-test
      findings demonstrated that children as young as 3 years of age can learn the
      inappropriateness of such requests even when coming from "good" people, although
      3 year olds had more difficulty recognizing inappropriate-touch requests compared
      to 4- and 5-year-old children. PRACTICE IMPLICATIONS: Results support the
      challenge of helping young children learn to recognize potential perpetrators,
      especially those described as "good" people.

PMID- 20684837
TI  - HO-1 modified mesenchymal stem cells modulate MMPs/TIMPs system and adverse
      remodeling in infarcted myocardium.
AB  - The present study was to determine the effects of the heme oxygenase-1 (HO-1)
      modified mesenchymal stem cells (MSCs) transplantation into acute MI hearts on
      normalizing the ratio of MMPs/TIMPs and remodeling in infarcted myocardium. HO-1
      was transfected into cultured MSCs using an adenoviral vector. 1 x 10(6) Ad-HO-1
      transfected MSCs (HO-1-MSCs) or Ad-Null-transfected MSCs (Null-MSCs) or PBS was
      respectively injected into rat hearts 1 h intramyocardially after myocardial
      infarction. The cardiac performance was significantly improved and left
      ventricular dilatation was significantly attenuated in HO-1-MSCs transplanted
      hearts. Moreover, a significant increase in microvessel density was observed in
      HO-1-MSCs transplanted hearts. TIMP2,3 expression in HO-1-MSCs transplanted
      hearts was significantly increased, and MMP2,9 expression in HO-1-MSCs
      transplanted hearts was significantly lower than Null-MSCs transplanted and PBS
      treated hearts. TIMP1 expression did not vary significantly. Null-MSCs
      transplantation did not decrease the expression of MMP2,9 significantly compared
      with PBS-treated hearts. The ratio of TIMP2 to MMP2, and TIMP3 to MMP9 in cell
      grafted hearts was increased significantly. HO-1-MSCs transplantation normalize
      the ratio of MMPs/TIMPs, contributing to the reversion of myocardial
      extracellular remodeling.

PMID- 20684844
TI  - Underascertainment of child abuse fatalities in France: retrospective analysis of
      judicial data to assess underreporting of infant homicides in mortality
      statistics.
AB  - OBJECTIVES: Test the hypothesis of an underestimation of infant homicides in
      mortality statistics in France; identify its causes; examine data from the
      judicial system and their contribution in correcting this underestimation.
      METHODS: A retrospective, cross-sectional study was carried out in 26 courts in
      three regions of France of cases of infant deaths submitted to the courts, 1996
      2000, with follow-up of their files until case closing (1996-2008). For each
      case, cause of death established by the courts was compared with ICD cause of
      death as coded in official mortality statistics. RESULTS: We examined 247 cases.
      Shortcomings in investigations were noted (autopsies: 75% of cases; fundus
      examination: 11%; diagnosis of sudden infant death syndrome [SIDS] without
      autopsy: 41%). Eighty deaths were considered homicides by the courts. Homicide
      rates in the court study are 2-3.6 times higher than those in mortality
      statistics. Nearly 1/3 of "accidental" deaths and 1/4 of deaths from unknown
      cause in mortality statistics are homicides. Mechanisms of underascertainment
      are: physicians' inappropriate death certification and underreporting of
      suspicious cases; inadequate investigation of cases; incomplete communication of
      final medical and forensic results to the mortality statistics department.
      CONCLUSIONS: In a country where neither transportation of the body to a hospital
      nor autopsy is obligatory, judicial data can make an important contribution to
      correcting mortality statistics. PRACTICE IMPLICATIONS: This study led to the
      first French protocol for investigating sudden unexpected deaths in infancy
      (SUDI). The protocol includes a physician "training" section focused on
      understanding the symptomatology and risk factors of violence, as well as the
      quality of death certification.

PMID- 20684845
TI  - Frogs, sentinels of DNA damage induced by pollution in Naples and the
      neighbouring Provinces.
AB  - Many DNA mutation-based diseases recognised in Campania have recently been
      related to toxic substances in illegal dumping areas. We performed a comet assay
      on edible frog erythrocytes to evaluate DNA damage. Differences in genotoxic
      parameters were observed among populations. We show that severe DNA damage
      occurred in the north Campania where the emergence of environmental waste
      exploded recently. Although a similar magnitude of genotoxic damage was observed
      in some southern populations, it is attributable to a massive pesticide pollution
      related to intensive farming. The frog species analysed seems to be a good
      bioindicator for detecting genotoxic effects of chemical environmental hazards.

PMID- 20684846
TI  - Copper generated reactive oxygen leads to formation of lysine-DNA adducts.
AB  - This work describes the addition of a lysine derivative to guanine base in a
      nucleoside, an oligonucleotide, and to a large DNA that occurs via oxidation by
      copper generated reactive oxygen species. Nucleophiles present during oxidation
      leads to the formation of adducts. In this work, 2'-deoxyguanosine is oxidized by
      copper generated reactive oxygen species in the presence of a lysine derivative,
      Nalpha-acetyl-lysine methyl ester. Under these conditions the guanidinohydantoin
      lysine adduct is observed in a relative yield of 27% when compared to other
      guanine oxidation products. MS(2) strongly supports that lysine is added to the 5
      position during the formation of guanidinohydantoin-lysine. A fourteen-nucleotide
      DNA duplex was oxidized under similar conditions. Digestion showed formation of
      the same guanidinohydantoin-lysine nucleoside. The reaction was then examined on
      a 392-nucleotide DNA substrate. Oxidation in the presence of the lysine ester
      showed adduct formation as stops in a primer extension assay. Adducts
      predominately formed at a 5'-GGG at position 415. Six of the seven sites that
      showed reaction greater than 3-fold above background were guanine sites. We
      conclude from this study that copper can catalyze the formation of DNA-protein
      adducts and may form in cells with elevated copper and oxidative stress.

PMID- 20684847
TI  - Evidence supporting a biological role for aluminum in brain chromatin compaction
      and epigenetics.
AB  - Averaging 8.1% (w/w) of the earth's crust, aluminum is the most highly abundant
      metal in our biosphere, yet has long been thought to serve no essential
      biological function. In aqueous solutions, aluminum salts and hydroxides are
      exceptionally potent aggregators of biological molecules, often coalescing
      molecular species to the point that they precipitate out of solution. A
      biological function for aluminum is proposed in which this abundant, high charge
      density metal cation has a significant role in biomolecular compaction.
      Sometimes, molecules ectopically aggregated by aluminum are associated with
      pathological conditions. The data further suggests that a specific consequence of
      'aluminum biocompaction' may be particularly important in the condensation of A+T
      rich chromatin domains, and in silencing the expression of specific kinds of
      genetic information.

PMID- 20684848
TI  - Psychosocial assessment and repetition of self-harm: the significance of single
      and multiple repeat episode analyses.
AB  - BACKGROUND: Self-harm is a common reason for presentation to the Emergency
      Department. An important question is whether psychosocial assessment reduces risk
      of repeated self-harm. Repetition has been investigated with survival analysis
      using various models, though many are not appropriate for recurrent events.
      METHODS: Survival analysis was used to investigate associations between
      psychosocial assessment following an episode of self-harm and subsequent
      repetition, including (i) one repeat, and (ii) recurrent repetition (<=5 repeats)
      using (a) an independent episodes model, and (b) a stratified episodes model
      based on a conditional risk set. Data were from the Multicentre Study on Self
      harm in England, 2000 to 2007. RESULTS: Psychosocial assessment following an
      index episode of self-harm was associated with a 51% (95% CI 42%-58%) decreased
      risk of a repeat episode in persons with no psychiatric treatment history, and
      26% (95% CI 8%-34%) decreased risk in those with a treatment history. For
      recurrent repetition, assessment was associated with a 57% (95% CI 51%-63%)
      decreased risk of repetition assuming independent episodes, and 13% (95% CI 1%
      24%) decreased risk accounting for ordering and correlation of episodes by the
      same person (stratified episodes model). All models controlled for age, gender,
      method, history of self-harm, and centre differences. LIMITATIONS: Some missing
      data on psychiatric treatment for non-assessed patients. CONCLUSIONS:
      Psychosocial assessment appeared to be beneficial in reducing the risk of
      repetition, especially in the short-term. Findings for recurrent repetition were
      highly dependent on model assumptions. Analyses should fully account for ordering
      and correlation of episodes by the same person.

PMID- 20684849
TI  - Factor structure of the CES-D in a sample of Spanish- and English-speaking
      smokers on the Internet.
AB  - Research on the Center for Epidemiological Studies-Depression Scale's (CES-D;
      Radloff, 1977) factor structure is mixed across diverse and international
      populations that differ from the one on which the scale was developed. This study
      examined the CES-D's factor structure in a large international sample of English
      (n=3827) and Spanish-speaking (n=13,629) smokers. A two-factor solution grouped
      into Positive and Negative factors emerged for the full English sample; the same
      two-factor solution emerged in the depressed English subsample identified with a
      separate screening instrument. A three-factor solution (Anxious/Somatic,
      Positive, and Negative) emerged for the full Spanish sample. Unlike the depressed
      English subsample, a different pattern of three factors (Negative, Positive, and
      Interpersonal Sensitivity) emerged in the depressed Spanish subsample. The
      findings in both languages differed from the original "four-factor" solution
      identified by Radloff (1977); they also suggest that the factor structure varies
      depending on language and depression status in international samples. The meaning
      of instruments and depressive symptoms may therefore vary across cultural and
      linguistic contexts.

PMID- 20684850
TI  - BCG vaccination failed to protect yearling African buffaloes (Syncerus caffer)
      against experimental intratonsilar challenge with Mycobacterium bovis.
AB  - Vaccination has been discussed as a practical option to control bovine
      tuberculosis in countries where a wildlife reservoir of the disease is present.
      African buffaloes (Syncerus caffer) are the main wildlife reservoir of
      Mycobacterium bovis in certain South African game parks and vaccination is not
      only the most promising but the only ethically acceptable control measure
      currently available. The use of Bacillus Calmette-Guerin vaccine (Pasteur strain)
      to vaccinate fourteen African buffalo yearlings and their reactions to subsequent
      intratonsilar challenge with a field strain of M. bovis are described. The BCG
      vaccine was administered twice intramuscularly, six weeks apart. All vaccinates
      and thirteen control buffaloes were euthanized and necropsies performed 9 months
      after the challenge. Standard sets of lymph nodes from the head, the thoracic
      cavity and abdomen were cultured and examined histopathologically. No significant
      reduction in number of lesions or severity of disease was noted, concluding that
      the BCG vaccine did not induce sufficient protection able to limit the shedding
      of organisms. The age of the buffaloes, route of vaccination and prior exposure
      to environmental mycobacteria are among the possible reasons for vaccination
      failure.

PMID- 20684851
TI  - In vitro human TGF-beta treatment converts CD4(+)CD25(-) T cells into induced T
      regulatory like cells.
AB  - In mammals, induced T regulatory cells (iTregs) are produced by treating
      CD4(+)CD25(-) cells in vitro with TGF-beta in the presence of anti-CD3 and IL-2.
      Chicken CD4(+)CD25(-) cells were treated in vitro with TGF-beta, anti-CD3, anti
      CD28 and IL-2 and analyzed for suppressive properties, IL-10 and IL-2 mRNA
      amounts. TGF-beta treatment decreased (P<0.01) CD4(+)CD25(-) cell proliferation
      by 45% at 5d of cell culture with no increase in dead cell population.
      CD4(+)CD25(-) cells treated with 5ng TGF-beta for 5d had 130-fold (P<0.01) more
      IL-10 and 104-fold (P<0.01) less IL-2 mRNA content than the 0ng TGF-beta treated
      groups. CD4(+)CD25(-) cells treated with 5ng TGF-beta for 5d suppressed (P<0.01)
      naive cell proliferation compared to the 0ng TGF-beta treated groups. The results
      suggest the presence of iTreg-like cells in avian species.

PMID- 20684852
TI  - Cancer on a pacemaker lead.

PMID- 20684853
TI  - Use of computer tomography coronary angiography in assessment of aorto-ostial
      coronary disease.

PMID- 20684854
TI  - Obstructive sleep apnea after myocardial infarction.

PMID- 20684856
TI  - New ruthenium(II) complexes with N-alkylphenothiazines: synthesis, structure, in
      vivo activity as free radical scavengers and in vitro cytotoxicity.
AB  - Three new complexes of the general formula L[RuCl(3)(DMSO)(3)] (1-3), where L =
      chlorpromazine hydrochloride, trifluoroperazine dihydrochloride or thioridazine
      hydrochloride, were prepared and characterized by elemental analysis and
      spectroscopic methods (FT-IR, UV-Vis, (1)H NMR and (13)C NMR). In addition, the
      crystal structure of the complex 2 containing trifluoroperazine dihydrochloride
      was solved by single crystal X-ray diffraction. The complex crystallizes in the
      monoclinic system, space group P2(1)/n, with a = 10.4935(7) A, b = 18.6836(12) A,
      c = 19.9250(13) A, beta = 98.448(2) degrees, V = 3864.0(4) A(3). The structure
      was refined to the agreement factors of R = 4.79%, R(w) = 11.23%. The effect of
      three different doses (0.4, 4.5 and 90.4 microM/kg bw) of complex 2 on superoxide
      dismutase (SOD) and catalase (CAT) activity was investigated under physiological
      conditions. Influence on nitrite production (NO(2)(-)) and the level of
      erythrocytes malondialdehyde (MDA) in rats blood was also evaluated. Complex 2
      did not affect the CAT enzyme activity in vivo and did not cause the hydroxyl
      radicals production. In the 0.4 and 4.5 microM/kg bw doses it showed almost the
      same or lower SOD activity and nitrite levels, while the dose of 90.4 microM/kg
      bw significantly increased these parameters. Finally, the cytotoxicity of
      complexes were assayed in four human carcinoma cell lines MCF-7, MDA-MB-453
      (breast carcinoma), SW-480 (colon adenocarcinoma) and IM9 (myeloma multiple
      cells). Antiproliferative activity in vitro with low IC(50) during 48 h of
      treatment was observed.

PMID- 20684857
TI  - In vitro anticancer screening and radiosensitizing evaluation of some new
      quinolines and pyrimido[4,5-b]quinolines bearing a sulfonamide moiety.
AB  - Sulfonamide bearing compounds possess many types of biological activities and
      have recently been reported to show substantial antitumor activity in vitro
      and/or in vivo. There are a variety of mechanisms for the anticancer activity,
      and the most prominent mechanism is the inhibition of carbonic anhydrase (CA)
      isozymes. The present work reports the synthesis of twenty novel quinoline and
      pyrimido[4,5-b]quinoline derivatives bearing a sulfonamide moiety. The new
      synthesized compounds were designed in compliance with the general pharmacophoric
      requirements for CA inhibiting anticancer drugs, as this may play a role in their
      anticancer activity. All the newly synthesized compounds were evaluated for their
      in vitro anticancer activity against human breast cancer cell line (MCF7).
      Compounds 6, 9 and 18 showed IC(50) values (72.9 microM, 72.1 microM and 71.9
      microM, respectively) comparable to that of the reference drug doxorubicin
      (IC(50) = 71.8 microM). On the other hand, compound 8 exhibited better activity
      than doxorubicin with an IC(50) value of 64.5 microM. Additionally, the most
      potent compounds 8 and 18 were evaluated for their ability to enhance the cell
      killing effect of gamma-radiation.

PMID- 20684859
TI  - Homology modeling and atomic level binding study of GABA(A) receptor with novel
      enaminone amides.
AB  - A series of novel enaminone amides with improved side effect were synthesized by
      Hogenkamp et al. To explore the action mechanisms of enaminone amides, the
      homology model of rat alpha1beta2gamma2 GABAR was generated using the cryo
      electron microscopy structure of the nAChR of Torpedo marmorata and the AChBP of
      Lymnaea stagnalis as the templates. Molecular docking and pharmacophore analyses
      allowed us to speculate the critical residues involving to the recognition of the
      ligands. The docking results indicated His128, Tyr186 and Tyr236 of alpha subunit
      were essential to form H-bond interactions contacts with the ligands. Specially,
      the N-substituents of enaminone amides as the sterically favored areas could form
      the important hydrophobic interactions with the residue Tyr186.

PMID- 20684858
TI  - 3D-QSAR studies of latrunculin-based actin polymerization inhibitors using CoMFA
      and CoMSIA approaches.
AB  - The marine-derived macrolide latrunculins A and B, from the Red Sea sponge
      Negombata magnifica, are known to reversibly bind actin monomers, forming 1:1
      complex with G-actin, disrupting its polymerization. Latrunculins have remarkable
      physiological properties and widely used as biochemical markers. Nevertheless, no
      QSAR studies have been developed for any kind of actin disruptors. In the present
      study, Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular
      Similarity Indices Analysis (CoMSIA) implemented in the SYBYL software packages
      were used to develop predictive 3D-QSAR models. Two alignment strategies were
      used to fit analyzed molecules to a suitable conformational template. By means of
      the SYBYL multifit alignment function, the best CoMFA and CoMSIA results
      presented cross-validated correlation coefficient values (q(2)) of 0.621 and
      0.659, and non-cross-validated values (r(2)) of 0.938 and 0.965, respectively.
      Comparable to multifit-derived models, CoMFA and CoMSIA 3D-QSAR models were also
      derived using a molecular alignment obtained by docking latrunculin derivatives
      into the ATP active site of actin. In addition to q(2), the predictive ability
      was validated using external test set of five compounds. The results of this
      study suggest that the established model has a strong predictive ability and can
      be prospectively used in the molecular design and action mechanism analysis of
      this kind of cytotoxic compounds.

PMID- 20684863
TI  - RNAi targeting EZH2 inhibits tumor growth and liver metastasis of pancreatic
      cancer in vivo.
AB  - The function of EZH2 in tumorigenesis and liver metastasis of pancreatic cancer
      has never been elucidated in vivo. EZH2 was overexpressed in pancreatic
      carcinomas and its overexpression was associated with tumor differentiation and
      pT status. Suppression of EZH2 caused a significant growth inhibition of
      pancreatic cancer cells in vitro and markedly diminished their tumorigenicity in
      vivo. Knock-down of EZH2 inhibited liver metastasis of pancreatic cancer in vivo.
      EZH2 has a crucial role in tumor growth and liver metastasis of pancreatic
      cancer.

PMID- 20684864
TI  - Brevimulticaecum sp. (Nematoda: Heterocheilidae) larvae parasitic in freshwater
      fish in the Pantanal wetland, Brazil.
AB  - During the study of metazoan parasites of freshwater fish in the Pantanal wetland
      (state of Mato Grosso do Sul, Brazil), third-stage larvae of Brevimulticaecum sp.
      were collected from the abdominal cavity, liver parenchyma, mesentery, skeletal
      muscles and stomach wall of the following species: Gymnotus inaequilabiatus,
      Hemisorubim platyrhynchos, Hoplias aff. malabaricus, Myleus levis,
      Pseudoplatystoma corruscans, Pygocentrus nattereri, Serrasalmus marginatus and
      Sorubim lima. The larvae exhibited the main characteristics of the genus
      Brevimulticaecum, such as short ventricular appendices and the position of
      excretory pore and excretory nucleus. This is the first report and description of
      larval specimens of Brevimulticaecum parasitic in these hosts, which are fish
      species distributed throughout South America.

PMID- 20684865
TI  - Phenotypic and genotypic characterisation of benzimidazole susceptible and
      resistant isolates of Haemonchus contortus.
AB  - The study was designed to compare the in vitro egg hatch test (EHT) and molecular
      allele-specific polymerase chain reaction PCR (AS-PCR) methods as tools for
      detection of benzimidazole resistance in Haemonchus contortus, a nematode
      parasite of small ruminants. Comparisons were made during the course of an
      experimental infection and changes in EHT and AS-PCR were monitored to measure
      the correlation between in vitro and molecular tests. Both methods were carried
      out according to World Association for the Advancement of Veterinary Parasitology
      (WAAVP) recommendations. The molecular test was used to discriminate TAC/TTC
      polymorphism in the beta-tubulin 200 codon of eight (four resistant and four
      susceptible) isolates of H. contortus. Using DNA from 100 third-stage larvae, the
      polymerase chain reaction (PCR)-based analysis revealed a decrease of the
      homozygous TTC/TTC genotype and an increase in heterozygous TTC/TAC and
      homozygous TAC/TAC individuals in all resistant isolates. Both methods showed
      comparable and reliable results with regard to detection of benzimidazole
      resistance. The molecular test has an advantage over the EHT because of its
      higher sensitivity. On the other hand, EHT is less time-consuming, allows
      reliable detection of <10% resistance allele frequency and is fairly reliable for
      the detection of benzimidazole resistance under field conditions.

PMID- 20684867
TI  - Antimicrobial resistance in Campylobacter coli selected by tylosin treatment at a
      pig farm.
AB  - Limited knowledge is available regarding the dynamics of macrolide resistance
      under farm conditions with natural Campylobacter populations. We examined the
      dynamics of antimicrobial resistance in Campylobacter coli at a large pig farm.
      Faeces were sampled from untreated sows and piglets (n=57), weaned pigs treated
      with tylosin (n=68) and pigs of the same group 3-5 weeks after withdrawal of
      tylosin (n=15). Additionally, 48 weaned pigs were sampled after tylosin had not
      been administered for 7 months at the farm. MICs for seven antimicrobials were
      determined, isolates were genotyped by PFGE and mutations conferring macrolide
      resistance were identified. Resistance to at least one antimicrobial agent was
      higher (P<0.001) in the isolates from the treated pigs (30 of 56) than in those
      from the untreated animals (2 of 40). Resistance to ciprofloxacin, erythromycin,
      nalidixic acid and streptomycin was higher (P<0.05) in the isolates from the
      treated pigs than in those from the untreated animals. All 14 erythromycin
      resistant isolates studied (MIC >= 512 MUg/ml) contained mutation A2075G in 23S
      rRNA. Resistance against at least one antimicrobial was significantly lower
      (P<0.05) when tylosin had not been administered for 7 months. Resistance to
      erythromycin and streptomycin also decreased (P<0.05). PFGE analysis revealed a
      change of genotypes induced by tylosin treatment. In conclusion, tylosin
      treatment of pigs selected for a high-level of resistance to erythromycin and
      resistance to ciprofloxacin, nalidixic acid and streptomycin also increased in C.
      coli isolates within a few days.

PMID- 20684868
TI  - Fatal canine distemper infection in a pack of African wild dogs in the Serengeti
      ecosystem, Tanzania.
AB  - In 2007, disease related mortality occurred in one African wild dog (Lycaon
      pictus) pack close to the north-eastern boundary of the Serengeti National Park,
      Tanzania. Histopathological examination of tissues from six animals revealed that
      the main pathologic changes comprised interstitial pneumonia and suppurative to
      necrotizing bronchopneumonia. Respiratory epithelial cells contained numerous
      eosinophilic intracytoplasmic inclusion bodies and multiple syncytial cells were
      found throughout the parenchymal tissue, both reacting clearly positive with
      antibodies against canine distemper virus (CDV) antigen. Phylogenetic analysis
      based on a 388 nucleotide (nt) fragment of the CDV phosphoprotein (P) gene
      revealed that the pack was infected with a CDV variant most closely related to
      Tanzanian variants, including those obtained in 1994 during a CDV epidemic in the
      Serengeti National Park and from captive African wild dogs in the Mkomazi Game
      Reserve in 2000. Phylogenetic analysis of a 335-nt fragment of the fusion (F)
      gene confirmed that the pack in 2007 was infected with a variant most closely
      related to one variant from 1994 during the epidemic in the Serengeti National
      Park from which a comparable fragment is available. Screening of tissue samples
      for concurrent infections revealed evidence of canine parvovirus, Streptococcus
      equi subsp. ruminatorum and Hepatozoon sp. No evidence of infection with Babesia
      sp. or rabies virus was found. Possible implications of concurrent infections are
      discussed. This is the first molecular characterisation of CDV in free-ranging
      African wild dogs and only the third confirmed case of fatal CDV infection in a
      free-ranging pack.

PMID- 20684869
TI  - Post-mortem diagnosis of anaphylaxis: A difficult task in forensic medicine.
AB  - The lack of reliable laboratory biomarkers and common standard definitions of
      signs and symptoms represents the main problem for clinicians when a suspected
      anaphylactic event must be diagnosed, while a post-mortem diagnosis of
      anaphylaxis is often a very difficult task in forensic medicine. Significant
      necroscopic signs as well as the data reported from witnesses or medical records
      may be absent, biological fluids as blood or urine may be unavailable or under
      thanatological modifications. The aim of this review is to focus on the
      diagnostic difficulties with which coroners and forensic pathologists have to
      cope when a confirmation of anaphylactic death is required by judicial
      authorities. Investigation methods for a prudent forensic diagnosis of
      anaphylactic death as well as the need of new potential laboratory or
      histological investigation techniques coming from immunological research are
      discussed too.

PMID- 20684870
TI  - Association of age, health literacy, and medication management strategies with
      cardiovascular medication adherence.
AB  - OBJECTIVE: To examine patients' use of medication management strategies (e.g.,
      reminders, pill boxes), and to determine how their use influences the
      relationship between patient characteristics and medication adherence. METHODS:
      Retrospective and cross-sectional study of 434 patients with coronary heart
      disease, examining both refill adherence and self-reported adherence. RESULTS:
      The most common strategy for managing refills was seeing a near empty pill bottle
      (89.9%), and for managing daily medications, it was associating medications with
      daily events (80.4%). Age<65 (OR = 1.7), as well as marginal (OR = 2.0) or
      inadequate health literacy (OR = 1.9), was independently associated with low
      refill adherence. Patients <65 also had lower self-reported adherence (OR = 1.8).
      Adjustment for use of medication management strategies did not substantially
      change these relationships. Reliance on reminders from friends or family to take
      medications, or waiting to refill a medicine only when the bottle was near empty,
      each were associated with 3-fold greater odds of non-adherence. CONCLUSION: Age
      <65 and marginal or inadequate health literacy were independently associated with
      medication non-adherence. Use of medication management strategies did not explain
      these relationships. PRACTICE IMPLICATIONS: The strategies which patients report
      using to assist with managing medication refills and daily medication use may be
      ineffective.

PMID- 20684871
TI  - Patients' sense of relationship with breast cancer surgeons: the relative
      importance of surgeon and patient variability and the influence of patients'
      attachment style.
AB  - OBJECTIVE: We examined to what extent variability in breast cancer patients'
      sense of relationship with their surgeons was attributable to patient vs surgeon
      variation and we examined the role of one patient characteristic: attachment
      style. METHODS: Women (N=133) due to undergo surgery for breast cancer with one
      of six surgeons self-rated their relationship with the surgeon, using the Working
      Alliance Inventory, and indicated their adult attachment style (secure vs
      insecure). Multilevel analysis of alliance scores quantified variance components
      at patient and surgeon levels and tested the relationship with attachment.
      RESULTS: Variability in alliance was overwhelmingly at the patient level.
      Alliance was greater in securely than non-securely attached patients, although
      this influence was small. CONCLUSION: Variability in quality of clinical
      relationships after breast cancer diagnosis largely reflects variation between
      individual patients, not surgeons. Although patients' attachment style is
      significant, its role is modest. More influential patient characteristics need to
      be identified. PRACTICE IMPLICATIONS: Breast cancer patients report a strong
      relationship with their surgeons. Because differences between surgeons make only
      a small contribution to variability in relationship, it should be a priority to
      identify and address the characteristics or behaviours at the level of individual
      patients that are associated with poorer relationships.

PMID- 20684873
TI  - Decision support in heart failure through processing of electro- and
      echocardiograms.
AB  - OBJECTIVE: Signal and imaging investigations are currently key components in the
      diagnosis, prognosis and follow up of heart diseases. Nowadays, the need for more
      efficient, cost-effective and personalised care has led to a renaissance of
      clinical decision support systems (CDSSs). The purpose of this paper is to
      present an effective way of achieving a high-level integration of signal and
      image processing methods in the general process of care, by means of a clinical
      decision support system, and to discuss the advantages of such an approach. From
      the wide range of heart diseases, heart failure, whose complexity best highlights
      the benefits of this integration, has been selected. METHODS: After an analysis
      of users' needs and expectations, significant and suitably designed image and
      signal processing algorithms are introduced to objectively and reliably evaluate
      important features involved in decisional problems in the heart failure domain.
      Then, a CDSS is conceived so as to combine the domain knowledge with advanced
      analytical tools for data processing. In particular, the relevant and significant
      medical knowledge and experts' knowhow are formalised according to an ontological
      formalism, suitably augmented with a base of rules for inferential reasoning.
      RESULTS: The proposed methods were tested and evaluated in the daily practice of
      the physicians operating at the Department of Cardiology, University Magna
      Graecia, Catanzaro, Italy, on a population of 79 patients. Different scenarios,
      involving decisional problems based on the analysis of biomedical signals and
      images, were considered. In these scenarios, after some training and 3 months of
      use, the CDSS was able to provide important and useful suggestions in routine
      workflows, by integrating the clinical parameters computed through the developed
      methods for echocardiographic image segmentation and the algorithms for
      electrocardiography processing. CONCLUSIONS: The CDSS allows the integration of
      signal and image processing algorithms into the general process of care. Feedback
      from end-users has been positive.

PMID- 20684874
TI  - Retinoic acid retards fetal and hindlimb skeletal development asymmetrically in a
      retinoic acid-induced clubfoot model.
AB  - Retinoic acid (RA) has been shown to induce congenital clubfoot in animal models,
      but it is unknown whether the effect of RA on the formation of clubfoot in vivo
      results from generalized growth retardation or from the specific effects of
      hindlimb skeletal development. Our experimental research was based on a clubfoot
      model treated by maternal administration of RA (120, 130 or 140 mg/kg body
      weight) as an intragastric dose on embryonic day 10 (E10), and a control group
      was administered with an equivalent dose of solvent. Prenatal RA exposure reduced
      fetal body weight, length and skeletal ossification of the hindlimb compared with
      the control fetuses in a dose-dependent manner. The normal development curves
      indicated that the RA-exposed fetuses showed delayed increase in body weight and
      skeletal ossification development. However, there was no uniform effect on the
      skeletons of the hindlimb, not least retardation in ossification and induction
      malformation on the talus and calcaneus. Our results demonstrated that prenatal
      RA exposure had retardation effects on the developing hindlimb skeleton that was
      independent of those on the overall fetal growth. The normal skeletal
      ossification showed that the talus and calcaneus were poorly ossified and they
      were delayed by almost one day in the RA 120 mg/kg group. Therefore, during the
      susceptible stages, different regions of the limb bud responded differently to
      the teratogenic effects of RA.

PMID- 20684875
TI  - Arylnaphthalene lignans from Taiwania cryptomerioides as novel blockers of
      voltage-gated K+ channels.
AB  - Lignans are natural phytochemicals which exhibit multiple pharmacological effects
      such as anti-inflammation, antivirus and anti-tumor activities. Whether they have
      effects on neural tissues and ion channels is still unknown. The effects of
      several arylnaphathalene lignans purified from Taiwania cryptomerioides on
      voltage-gated K(+) (Kv) channels in mouse neuroblastoma N2A cells were examined.
      These lignans included Taiwanin E, helioxanthin (HXT) and diphyllin. All lignans
      showed inhibitory effects on Kv channels and HXT was the most potent compound
      (IC(50)=1.7 MUM). The mechanism of HXT block was further investigated. Its action
      was found to be extracellular but not intracellular. HXT accelerated current
      decay, caused a left-shift in steady-state inactivation curve but had no effect
      on voltage-dependence of activation. HXT block was unaffected by intracellular
      K(+) concentrations. Further, it did not affect ATP-sensitive K(+) channels. Our
      data therefore suggest that HXT is a potent and specific blocker of Kv channels,
      possibly with an inhibitory mechanism involving acceleration of slow
      inactivation.

PMID- 20684876
TI  - Multicomponent polymeric micelles based on polyaspartamide as tunable fluorescent
      pH-window biosensors.
AB  - PHEA-PEG(5000)-C(16) is a polyaspartamide polymer with appended hydrophilic
      PEG(5000) functions and hydrophobic n-C(16) units forming biocompatible micelles
      with a CAC as low as 1.8 * 10(-7) M. The protonation and acidity constants of the
      polymer's amino and carboxylic groups have been determined by potentiometric
      titrations at five different concentrations higher than CAC, finding
      concentration-independent values. Viscosity and polarity of the micellar core
      have been investigated by means of fluorescent probes, finding local values
      comparable to those of pure toluene and to the core of sodium dodecyl sulphate
      micelles, independently on the protonation degree of the polymer. The fluorophore
      pyrene, the lipophilic N,N'-dimethyl-N"-dodecylamine and 2-dodecylpyridine self
      assemble in the hydrophobic core of PHEA-PEG(5000)-C(16) micelles originating a
      micellar device that behaves as a rare "off-on-off" fluorescence sensor for pH
      windows, with no interference by the amino and carboxylic functions of the
      polymer. The "on" state of the sensor includes the physiological 6-8 pH interval,
      and can be finely shifted in both directions of the pH axis by comicellization of
      charged cosurfactants. Dialysis experiments demonstrate that the micellar device
      exibits an efficient retention ability of all molecular components, including
      cosurfactants, thus candidating for in vivo use.

PMID- 20684877
TI  - Regulation of cell identity by plant Polycomb and trithorax group proteins.
AB  - Descendants of stem cells have to make the decision whether to differentiate or
      whether to maintain a proliferation-competent state. This decision is mediated by
      the balanced activity of Polycomb group (PcG) and trithorax group (trxG)
      proteins. PcG proteins keep genes in a transcriptional repressed state while trxG
      proteins antagonize PcG activity and maintain genes in a transcriptional active
      state. PcG proteins act as global regulators of genomic programs that prevent the
      untimely expression of genes during development and, therefore, ensure that a
      correct set of genes is active during defined stages of development. Here we will
      discuss the recent progress in our understanding of the action of PcG proteins
      and the factors that antagonize PcG function to control cell fate and
      differentiation during plant development.

PMID- 20684878
TI  - Landfill leachate pollutant removal performance of a novel biofilter packed with
      mixture medium.
AB  - Landfill leachate pollutants were treated in a biofilter filled with a mixture of
      aged refuse and slag, and the performance was compared with those reactors filled
      solely with either medium. Cultural counting method showed that bioreactor filled
      with slag had the highest amount of nitrifying bacteria, while polymerase chain
      reaction-denaturing gradient gel electrophoresis method showed that reactor
      filled with both media had the highest bacterial community diversity. Particle
      size distributions measurement showed that slag contained less fine particles
      than aged refuse, which provided better permeability. The reactor containing both
      media exhibited a high efficiency in removal of pollutants, and a higher
      resistance to shock loading and low temperature compared with single-medium
      reactors. It also overcame both the poor permeability of aged refuse filling and
      the low bacteria diversity of slag. The study shows that a mixture of aged refuse
      and slag as a new biofilter medium for leachate pollutant removal is technically
      viable.

PMID- 20684879
TI  - Improvement of straw surface characteristics via thermomechanical and chemical
      treatments.
AB  - This study focused on effects of thermomechanical treatment, acid hydrolysis and
      enzymatic hydrolysis of rice straw fibre on its water resistant. Xylose and
      arabinose yields were 19.97% and 2.55%, respectively with thermomechanical
      treatment, 24.35% and 3.18% with acid hydrolysis, and 20.11% and 2.73% with
      enzymatic hydrolysis. The acid treatment dissolved hemicellulose significantly,
      leading to more fines and more voids in the surface of the rice straw fibre. The
      fines showed a higher water retention value (WRV) of 137.41% and exhibited higher
      swelling capacity. An increase in acid loading resulted in the increased WRV. The
      enzymatic hydrolysis increased the crystallinity of cellulose, but no significant
      correlation could be found between the chemical component and the water
      resistance of the rice straw fibre.

PMID- 20684880
TI  - Dual tunnel medial patellofemoral ligament reconstruction for patients with
      patellar dislocation using a semitendinosus tendon autograft.
AB  - The purpose of this study was to describe a safer and more anatomical technique
      of MPFL reconstruction and to report the short-term results. The subjects
      included 20 patients with patellar dislocation with a mean age of 23. The
      operation was performed using a double-looped autogenous semitendinosus tendon
      graft. Two small bone tunnels were made at the medial edge of the patella,
      mimicking the wide patellar insertion of the MPFL and a bone tunnel was made at
      the femoral insertion site. The free ends of the graft attached to the patella
      and the loop end was fixed to the femoral side. Five patients were available for
      follow-up interviews by telephone and the remaining 15 were directly examined by
      physical examination and radiographic evaluation at 2 years or longer
      postoperatively. The average follow-up period was 30 months. Re-dislocation or
      patellar fracture was not seen in any patients. The average Kujala's score was 96
      with a range from 84 to 100. Six patients were classified as excellent and 14 as
      good, according to the Crosby and Insall grading system. Radiographically,
      narrowing of the patellofemoral joint space was observed in 2 cases with previous
      osteochondral fracture out of those who were directly examined. The dual tunnel
      MPFL reconstruction produces favorable results in subjective and functional
      assessment of outcome without complications.

PMID- 20684882
TI  - The interactions of cisplatin and DNA studied by atomic force microscopy.
AB  - The interactions of the several linear DNA fragments and cisplatin at different
      concentrations and incubation time have been studied by atomic force microscopy.
      When equal volume of 2mM cisplatin and 5ng/microl 1134bp DNA fragment were
      incubated for 30min, 1h, 2h and 3h, the observed DNA were gradually changed from
      the extended chains to the bending structures, the worm-like structures and flat
      particles. The formation of these structures can be attributed to the
      coordination and electrostatic interactions by binding of cisplatin on DNA. When
      longer DNA fragments such as pBR322/pstI DNA (4361bp) and lambda DNA (48502bp)
      were used for interacting with cisplatin in the same condition, the observed DNA
      molecules tended to form many loop structures. The differences of the
      interactions between long and short DNA can be ascribed to the strong
      intramolecular interactions within the long DNA fragment. When the relative low
      concentration of cisplatin (100micromol/l) was used in the experiments, the
      observed DNA tended to bend along its chains. Furthermore, the measured contour
      length and the calculated persistent length of cisplatin-DNA were gradually
      decreased with the incubated time. All of these AFM results revealed that the
      cisplatin-DNA interactions in vitro can be influenced by the concentration and
      the initial state of cisplatin, the length of DNA fragment and the reaction time.

PMID- 20684881
TI  - Effects of medial meniscal posterior horn avulsion and repair on meniscal
      displacement.
AB  - Medial meniscal posterior root avulsion (MMRA) leads to deleterious alteration of
      medial joint compartment loading profiles and increased risk of medial
      degenerative changes. Surgical repair restores more normal biomechanics to the
      knee. Our hypothesis is that MMRA will cause medial meniscal (MM) extrusion and
      gap formation between the root attachment site and MM. Meniscal root repair will
      restore the ability of the meniscus to resist extrusion, and reduce gap formation
      at the defect. Seven fresh frozen human cadaveric knees were dissected and
      mechanically loaded using a servo-hydraulic load frame (MTS (r)) with 0 and 1800
      N. The knees were tested under three conditions: native, avulsed, and repaired.
      Four measurements were obtained: meniscal displacement anteriorly, medially,
      posteriorly, and gap distance between the root attachment site and MM after
      transection and repair. The medial displacement of the avulsed MM (3.28 mm) was
      significantly greater (p < 0.001) than the native knee (1.60mm) and repaired knee
      (1.46 mm). Gap formation is significantly larger in the avulsed compared to
      repaired state at 0 (p < 0.02) and 1800N (p < 0.02) and also larger with loading
      in both avulsed (p < 0.05) and repaired (p < 0.02) conditions. Therefore, MMRA
      results in MM extrusion from the joint and gap formation between the MM root and
      the MM. Subsequent surgical repair reduces meniscal displacement and gap
      formation at the defect.

PMID- 20684884
TI  - Resistance to HER2 inhibitors: is addition better than substitution? Rationale
      for the hypothetical concept of drug sedimentation.
AB  - Twenty years were passed between the discovery of oncogene HER2, the description
      of its implication in mammary carcinogenesis, and the development of specific
      targeted therapies. To date, trastuzumab and lapatinib are the two anti-HER2
      targeted therapies commonly used, demonstrating therapeutic effects. Although
      their clinical efficacy seems to be exclusively related to the amplification of
      the HER2 gene or to the overexpression of the protein, these factors are not
      sufficient since tumors can develop resistance. Because of a better knowledge in
      those mechanisms of resistance, novel therapeutic agents could help to bypass
      them. How should these be used with respect to current anti-HER2 targeted
      therapies? Recent notions such as oncogene addiction, tumor cell dormancy and
      residual disease led us to propose a new entity that we named the "sedimentation
      strategy", in which distinct targeted approaches are summed during the treatment
      of metastatic breast cancer patients.

PMID- 20684885
TI  - Preimplantation genetic diagnosis (PGD) for a treatable disorder: Gaucher disease
      type 1 as a model.
AB  - BACKGROUND: Preimplantation genetic diagnosis (PGD) is a technique that enables
      identification of unaffected embryos prior to in vitro fertilization (IVF)
      transfer in couples at risk for a Mendelian disorder. Most cases involve severe
      genetic diseases with neurological features and/or major malformations. We
      present two couples in which PGD was performed for prevention of type 1 Gaucher
      disease, a non-neuronopathic, non-lethal disorder. MATERIALS AND METHODS: We
      developed a multiplex fluorescent PCR protocol, simultaneously amplifying the
      familial mutations and eight closely spaced, highly polymorphic informative
      microsatellite markers surrounding the gene, to be used for PGD analysis.
      RESULTS: Couple #1 mother was homozygous for the N370S mutation and the father
      carried the 84GG mutation; their first daughter receives specific Gaucher
      therapy. One PGD cycle resulted in seven embryos of which four had the paternal
      wild type allele; two were transferred resulting in a healthy baby boy born at
      term. Couple #2, each a carrier (N370S and R359Q), whose first-born child had
      died (age 5years) of Gaucher disease, underwent 7 PGD cycles. Only one cycle
      resulted in a clinical pregnancy but a miscarriage was followed at 10weeks.
      CONCLUSIONS: PGD is an effective and accurate method for preventing Gaucher
      disease type I in carrier couples. Since this disease is treatable, special
      ethical considerations and careful selection of couples should be performed.

PMID- 20684886
TI  - Enzyme replacement therapy "drug holiday": results from an unexpected shortage of
      an orphan drug supply in Australia.
AB  - The development of recombinantly manufactured enzyme replacement therapy (ERT)
      has revolutionised the management of some inherited disorders of metabolism.
      Gaucher disease was the first lysosomal storage disorder for which ERT became
      commercially available and ERT remains first-line treatment for affected
      individuals. In Australia, 70 patients with Gaucher disease are treated through a
      centrally administered Australian Government national program known as the Life
      Savings Drug Program (LSDP). Imiglucerase (Cerezyme), manufactured by Genzyme
      Corporation, is the only ERT currently registered in Australia for the treatment
      of Gaucher disease. In June 2009, Genzyme Corporation announced the detection of
      a virus in its Allston Landing manufacturing facility which resulted in
      inventories of imiglucerase being insufficient to meet projected global demand.
      The Australian Government sought advice from its Gaucher Disease Advisory
      Committee (GDAC) on recalculating patient doses in order to ration available
      imiglucerase to those most in need on a clinical severity basis. Management of
      this rationing process was urgent and required extensive investigation to develop
      a clinical severity hierarchy, to review available imiglucerase stock spread
      across multiple pharmacies, to implement a strategy for redistributing available
      imiglucerase according to specific patients' recalculated doses, to advise
      treating doctors and patients concerning these changed circumstances and to
      consider new monitoring schedules during the drug shortage phase. A cohort of 24
      patients was withdrawn from therapy, 22 of whom had no discernable clinical
      adverse effect. This experience suggests that short-term studies of maintenance
      therapy without a no-treatment arm may lead to erroneous conclusions and that
      some patients may have treatment holidays or delayed infusions without short-term
      adverse outcomes.

PMID- 20684887
TI  - Short-term withdrawal from imiglucerase: what can we learn from it?

PMID- 20684888
TI  - Detection and analysis of reactive oxygen species (ROS) generated by nano-sized
      TiO2 powder under ultrasonic irradiation and application in sonocatalytic
      degradation of organic dyes.
AB  - Recently, the sonocatalytic technology using various semiconductors combined with
      ultrasonic irradiation has been received much attention to solve the
      environmental problems. In this paper, nano-sized titanium dioxide (TiO(2))
      powder as a sonocatalyst was irradiated by ultrasound and the generation of
      reactive oxygen species (ROS) during sonocatalytic reaction process has been
      estimated by the method of Oxidation-Extraction Photometry (OEP). That is, the
      1,5-diphenylcarbohydrazide (DPCI) can be oxidized by ROS into diphenylcarbonzone
      (DPCO), which can be extracted by the mixed solution of benzene and carbon
      tetrachloride and show the great absorbance at 563 nm wavelength. The synergistic
      effect of TiO(2) and ultrasonic irradiation was estimated and some influencing
      factors, such as ultrasonic irradiation time and TiO(2) addition amount on the
      generation of ROS were reviewed. The results indicate that the quantities of
      generated ROS increase with the increase of ultrasonic irradiation time and
      TiO(2) addition amount. Moreover, the relationship between quantities of
      generated ROS and DPCI concentration was also studied. And then, several
      quenchers were used to determine the kind of the generated ROS. At last, the
      researches on the sonocatalytic degradation of organic dyes and the corresponding
      reaction kinetics have also been performed, which is found to follow the pseudo
      first-order kinetics approximately. This paper may offer some important subjects
      for broadening the applications of sonocatalytic technology.

PMID- 20684891
TI  - Cardiac rehabilitation staff views about discussing sexual issues with coronary
      heart disease patients: a national survey in Ireland.
AB  - BACKGROUND: While a healthy sexual life is regarded as an important aspect of
      quality of life, sexual counselling from healthcare providers for cardiac
      patients has received little attention in the literature. AIM: To document
      current practice and assess the needs of cardiac rehabilitation service providers
      in Ireland with regard to sexual assessment and management for patients. METHODS:
      Cardiac rehabilitation staff in all relevant centres in Ireland responded to a
      postal questionnaire. Sexual health management was assessed by a series of
      questions on current practice, staff attitudes, beliefs and perceived barriers to
      discussing sexual problems. RESULTS: Staff (N=60; 61% response rate) reported a
      lack of assessment and counselling protocols for addressing sexual health
      problems, with little or no onward referral system available. Results also
      suggest staff believe that patients do not expect them to ask about their sexual
      concerns. Barriers reported included an overall lack of confidence (45%),
      knowledge (58%) and training (85%). CONCLUSION: Development of guidelines,
      assessment protocols and training for cardiac rehabilitation staff are essential
      in the area of sexual health problems in order to improve the quality of services
      for patients with coronary heart disease.

PMID- 20684894
TI  - Pain physiology education improves pain beliefs in patients with chronic fatigue
      syndrome compared with pacing and self-management education: a double-blind
      randomized controlled trial.
AB  - OBJECTIVE: To examine whether pain physiology education was capable of changing
      pain cognitions and pain thresholds in patients with chronic fatigue syndrome
      (CFS) and chronic widespread pain. DESIGN: Double-blind randomized controlled
      trial. SETTING: Specialized chronic fatigue clinic in university hospital.
      PARTICIPANTS: A random sample of patients (N=48) with CFS patients (8 men, 40
      women) experiencing chronic pain, randomly allocated to the control group (n=24)
      or experimental group (n=24). Two women in the experimental group did not
      complete the study because of practical issues (lack of time and restricted
      mobility). INTERVENTIONS: One individual pain physiology education session
      (experimental) or 1 pacing and self-management education session (control). MAIN
      OUTCOME MEASURES: Algometry, the Neurophysiology of Pain Test, and questionnaires
      evaluating pain cognitions-the Pain Coping Inventory, the Pain Catastrophizing
      Scale, and the Tampa Scale for Kinesiophobia-version CFS-were completed
      immediately before and immediately after the intervention. RESULTS: After the
      intervention, the experimental group demonstrated a significantly better
      understanding of the neurophysiology of pain (P<.001) and a reduction of the Pain
      Catastrophizing Scale subscale "ruminating" (P=.009) compared with controls. For
      these variables, moderate to large Cohen d effect sizes were revealed (.79-2.53).
      CONCLUSIONS: A 30-minute educational session on pain physiology imparts a better
      understanding of pain and brings about less rumination in the short term. Pain
      physiology education can be an important therapeutic modality in the approach of
      patients with CFS and chronic pain, given the clinical relevance of inappropriate
      pain cognitions.

PMID- 20684895
TI  - Quantification of the effects of transcutaneous electrical nerve stimulation with
      functional magnetic resonance imaging: a double-blind randomized placebo
      controlled study.
AB  - OBJECTIVE: To evaluate the effects of transcutaneous electric nerve stimulation
      (TENS) by using functional magnetic resonance imaging (fMRI) in patients with
      carpal tunnel syndrome (CTS). DESIGN: Randomized controlled trial. SETTINGS:
      University medical center and an outpatient imaging center. PARTICIPANTS: Female
      patients with CTS (n=20) were randomized into 2 groups receiving either TENS
      (n=10) or sham TENS (n=10). In both groups, an initial baseline fMRI session was
      performed via stimulating digits 2, 5, and 3 in turn, 1 scan run for each. TENS
      versus sham TENS treatment was given, and a repeat imaging was performed starting
      20 minutes after the treatment as follows: second finger on the 20th minute,
      fifth finger on the 25th minute (ulnar nerve innervated control finger), and
      third finger on the 30th min. INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURE: Differences in fMRI activation between the 2 groups were evaluated.
      RESULTS: Our results demonstrated that 20 to 25 minutes after TENS treatment-but
      not in the sham TENS group-a significant fMRI signal decrease for digit 2 (post
      TENS vs baseline) was observed in the secondary somatosensory regions,
      ipsilateral primary motor cortex (M1), contralateral supplementary motor cortex
      (SMA), contralateral parahippocampal gyrus, contralateral lingual gyrus, and
      bilateral superior temporal gyrus. Measurements on the 25th to 30th minutes for
      digit 5 were similar between the groups, with presence of activities in areas
      other than generally activated regions because of painful stimuli. Thirty to 35
      minutes after TENS treatment, a significant fMRI signal decrease for digit 3 was
      detected in the contralateral M1 and contralateral SMA only in the TENS group.
      CONCLUSIONS: Our findings showed that TENS treatment significantly decreased the
      pain-related cortical activations caused by stimulation of the median nerve
      innervated fingers up to 35 minutes after treatment.

PMID- 20684896
TI  - Wheelchair-related falls in veterans with spinal cord injury residing in the
      community: a prospective cohort study.
AB  - OBJECTIVES: (1) To determine the incidence of wheelchair falls and fall-related
      injuries in persons with spinal cord injury (SCI) living in the community. (2) To
      predict wheelchair-related falls and associated injuries from specific parameters
      including characteristics of the wheelchair user, wheelchair type and features,
      health care practices, wheelchair activities, and physical environment. DESIGN:
      This prospective cohort study followed participants monthly over 1 year; data
      were collected through surveys, interviews, performance testing, observation, and
      medical records. SETTING: Three Veterans' Administration hospitals. PARTICIPANTS:
      Convenience sample of community-dwelling persons with SCI who used a wheelchair
      as their primary means of mobility (N=702). INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURES: Self-reports of wheelchair falls and fall-related injuries,
      Wheelchair User Characteristics Survey, Health Status Checklist, Health-Related
      Behaviors, Zuckerman Sensation Seeking Scale, Wheelchair and Equipment-Related
      Behaviors, Wheelchair Characteristics, Wheelchair Skills Test, and Physical
      Environment Assessment. RESULTS: Of the 659 subjects who completed the study, 204
      participants (31%) reported 553 fall events, and 95 subjects (14%) were injured
      as a result of wheelchair falls. A logistic regression model for predicting
      wheelchair falls identified 6 significant risk factors: pain in previous 2
      months, alcohol abuse, greater motor function, history of previous fall, fewer
      SCI years, and shorter length of wheelchair. Eighty-two percent of the variance
      for wheelchair fall events was explained by these 6 variables. A logistic
      regression model for predicting injurious falls identified 4 significant risk
      factors: pain in previous 2 months, greater motor function, history of previous
      fall, and inaccessible home entrance. These 4 factors were able to explain 81% of
      the variance for injurious falls. CONCLUSIONS: This is the first study to
      determine the incidence of wheelchair-related falls in community-dwelling people
      with SCI who use a wheelchair. Results indicate the incidence of falls was 31%
      and injurious falls was 14%. Those at greatest risk can be predicted from some
      readily available information regarding their clinical status, wheelchair
      features, and home environment.

PMID- 20684897
TI  - Structural equation modeling of the relationships between participation in
      leisure activities and community environments by people with mobility
      impairments.
AB  - OBJECTIVE: To examine the linkages between the constructs of participation and
      the environment for a set of leisure activities (attending concerts, attending
      movies, attending sporting events). DESIGN: Self-report surveys of the influence
      of the environment on participation were analyzed using structural equation
      modeling. Temporal, evaluative, and health-related aspects of leisure activities
      were selected as latent variables associated with participation. The
      environmental construct consisted of the latent variables of the influence on
      participation of the natural, interpersonal, built, background, and supportive
      environments. SETTING: Midwestern United States. PARTICIPANTS: A purposive sample
      of people (N=604) with mobility limitations. INTERVENTION: None. MAIN OUTCOME
      MEASURES: Measures of relationships between participation in leisure activities
      and the environment of people with mobility limitations. RESULTS: Structural
      equation modeling can be an important tool for empirically examining the
      contributions of the component latent variables of participation and the
      environment. CONCLUSIONS: A model that fits participation by people with
      disabling conditions in their environment can provide guidance for community
      based interventions and person-based therapies.

PMID- 20684898
TI  - Posttraumatic stress disorder and spinal cord injury.
AB  - OBJECTIVES: To identify the prevalence of posttraumatic stress disorder (PTSD)
      after spinal cord injury (SCI) in a sample averaging over 2 decades postinjury at
      assessment. Related objectives are to confirm the factor structure, compare
      subscales with those reported in a nonclinical sample, and identify the
      relationship of PTSD with depression. DESIGN: Survey. SETTING: A medical
      university in the Southeastern United States. PARTICIPANTS: Participants were
      initially identified through specialty hospitals in the Midwest and Southeastern
      United States. A cohort of adults (N=927) with traumatic SCI of at least 1 year
      duration at enrollment in 2002 to 2003 and a minimum of 7 years at the time of
      assessment completed the study materials. INTERVENTIONS: Not applicable. MAIN
      OUTCOMES MEASURES: PTSD was measured by the Purdue Posttraumatic Stress Disorder
      Scale-Revised, and depression was measured by the Patient Health Questionnaire 9
      item. RESULTS: PTSD was reported by less than 10% of the participants. Item
      endorsement decreased as a function of years postinjury, primarily because of low
      rates of endorsement among those 21 or more years postinjury. Confirmatory factor
      analysis did not result in an acceptable fit for subscales, item sets, or factors
      previously reported in the literature. Participants scored higher than a
      nonclinical sample (reported in the literature) on the arousal and avoidance
      subscales but lower on the re-experiencing subscale. Item endorsement were lower
      for the first set of items that relate directly to the SCI itself, with the
      highest item endorsement for "have difficulty remembering important aspects of
      event." PTSD rarely occurred in the absence of a depressive disorder.
      CONCLUSIONS: PTSD does not appear to be highly prevalent in long-term SCI
      survivors, and endorsement of items related to re-experiencing and even recalling
      the injury are rare. Because SCI often is accompanied by mild traumatic brain
      injury, difficulty recalling the event may have an organic rather than
      psychologic component.

PMID- 20684899
TI  - Psychometric evaluation of the Rasch-based depression screening in patients with
      neurologic disorders.
AB  - OBJECTIVES: To provide a first evaluation of the Rasch-Based Depression Screening
      (DESC) in consecutive patients with neurologic disorders. DESIGN: Cross-sectional
      study. SETTING: Hospital specializing in neurologic disorders. PARTICIPANTS:
      Eligible patients (N=323; mean age +/- SD, 53.4+/-17.2y; 49.3% women) age 18
      years and older. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: DESC with
      2 parallel versions. RESULTS: Both versions of the DESC showed good item
      separation (DESC-I=4.96; DESC-II=4.94) and person separation (DESC-I=2.01; DESC
      II=2.14) as well as item separation reliability (DESC-I=.96; DESC-II=.96) and
      person separation reliability (DESC-I=.80; DESC-II=.82). All items fit the Rasch
      model (infit and outfit mean squares < or =1.3). There were no signs of violation
      of unidimensionality. One item of DESC-I showed differential item functioning
      because of age and 1 item because of sex. Parallel test reliability of the 2 DESC
      forms was r equal to .92. CONCLUSIONS: The DESC shows good psychometric
      characteristics that suggest high psychometric quality of the instrument in
      patients with neurologic disorders. Differential item functioning on single items
      needs further examination but should not substantially interfere with the valid
      interpretation of DESC sum scores.

PMID- 20684900
TI  - Measuring mobility limitations in children with cerebral palsy: development,
      scalability, unidimensionality, and internal consistency of the mobility
      questionnaire, MobQues47.
AB  - OBJECTIVES: To develop a questionnaire that specifically and comprehensively
      measures mobility limitations in children with cerebral palsy (CP) and to
      investigate certain psychometric properties (scalability, unidimensionality,
      internal consistency) of this questionnaire. DESIGN: Cross-sectional study.
      SETTING: Private physical therapy practices and outpatient departments of
      hospitals and rehabilitation centers. PARTICIPANTS: Children with CP undergoing
      physical therapy or rehabilitation. The Mobility Questionnaire, 47-item
      (MobQues47), was completed by the mothers of these children (N=323; mean age +/-
      SD, 7.1+/-2.9y; 57% boys; Gross Motor Function Classification levels: I [48%], II
      [26%], III [19%], IV [7%]). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
      Mokken scale analysis was used to investigate (1) scalability, indicating that
      the items form a scale; (2) unidimensionality, indicating that the items measure
      only 1 concept; and (3) internal consistency, indicating the degree of
      interrelatedness of the items. RESULTS: The MobQues47, made up of 47 items, was
      developed on the basis of 3 pilot studies and careful operationalization of the
      concept (or construct) of mobility limitations. The scalability (coefficient
      H=.70), unidimensionality, and internal consistency (coefficient rho=.99) of the
      MobQues47 were found to be very good. CONCLUSIONS: The MobQues47 is a
      unidimensional scale with excellent internal consistency that can be used to
      measure caregiver-reported mobility limitations in children with CP.

PMID- 20684901
TI  - Three-dimensional movement analysis of handwriting in subjects with mild
      hemiparesis.
AB  - OBJECTIVE: To investigate the effects of hemiparesis on handwriting using a 3
      dimensional movement analyzer. DESIGN: Comparative case study. SETTING:
      Ambulatory care clinic. PARTICIPANTS: Right-handed patients (n=25; mean age +/-
      SD, 62.3+/-10y) with mild right hemiparesis secondary to subcortical stroke, and
      age-matched (n=10; 65.6+/-13y) and age-unmatched (n=15; 32.4+/-10y) control
      subjects. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Time required to
      write a Japanese character of 2 different sizes and average speed of handwriting
      at the pen tip. Average radii of tracks of the moving pen tip, metacarpal head of
      the index finger, and distal end of the forearm during writing. Correlation
      coefficients of the instantaneous speed-time graph of the pen tip with that of
      the index finger and with that of the distal forearm during writing. RESULTS:
      Time for writing with the hemiparetic right hand was longer than that with the
      unaffected left hand (P=.05 approximately .03), while it was shorter in healthy
      control subjects (P=.07 approximately .05). In contrast with the left-hand
      writing, the track radius of the pen tip of the right-hand writing in patients
      with hemiparesis with normal joint position sense was significantly larger than
      that of the finger or distal forearm (P=.01). The finding was the same as in the
      young and elderly control subjects. This right-left difference disappeared in the
      patients with hemiparesis with position sense impairment. The correlation
      coefficient of speed between the pen tip and the finger was larger in right-hand
      than left-hand writing in the control and sensory-normative patients with
      hemiparesis even though the difference was significant only in the healthy
      elderly subjects (P=.03). Irrespective of the right or left hand use, the
      correlation coefficient between the pen tip and the finger or distal forearm
      significantly increased as the character size increased (P=.03 approximately 6
      x10(-6)) in all subjects and patients. However, this size-related difference was
      less significant in the patients with sensory impairment. CONCLUSIONS: The
      characteristics of handwriting movement by the dominant hand were preserved in
      patients with mild dominant-hand hemiparesis when joint position sense was
      normative but were lost in those with position sense impairment.

PMID- 20684902
TI  - Factor structure and predictive validity of somatic and nonsomatic symptoms from
      the patient health questionnaire-9: a longitudinal study after spinal cord
      injury.
AB  - OBJECTIVE: To investigate the factor structure and predictive validity of somatic
      and nonsomatic depressive symptoms over the first 2.5 years after spinal cord
      injury (SCI) using the Patient Health Questionnaire-9 (PHQ-9). DESIGN: Somatic
      and nonsomatic symptoms were assessed at baseline during inpatient
      hospitalization (average of 50 days after onset) and during 2 follow-ups (average
      of 498 and 874 days after onset). SETTING: Data were collected at a specialty
      hospital in the Southeastern United States and analyzed at a medical university.
      We performed time-lag regression between inpatient baseline and follow-up somatic
      and nonsomatic latent factors of the PHQ-9. PARTICIPANTS: Adults with traumatic
      SCI (N=584) entered the study during inpatient rehabilitation. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURE: PHQ-9, a 9-item measure of depressive symptoms.
      RESULTS: The inpatient baseline nonsomatic latent factor was significantly
      predictive of the nonsomatic (r=.40; P=.000) and somatic latent factors at the
      second follow-up (r=.29; P=.006), whereas the somatic factor at inpatient
      baseline did not significantly predict either factor. In contrast, when
      regressing latent factors between the 2 follow-ups, the nonsomatic factor
      predicted only the nonsomatic factor (r=.66; P=.002), and the somatic factor
      predicted only future somatic symptoms (r=.66; P=.000). In addition, the factor
      structure was not stable over time. Item analysis verified the instability of
      somatic items between inpatient baseline and follow-up and also indicated that
      self-harm at inpatient baseline was highly predictive of future self-harm.
      CONCLUSIONS: Nonsomatic symptoms are better predictors of future depressive
      symptoms when first assessed during inpatient rehabilitation, whereas somatic
      symptoms become stable predictors only after inpatient rehabilitation. Self-harm
      (suicidal ideation) is the most stable symptom over time. Clinicians should
      routinely assess for suicidal ideation and use nonsomatic symptoms when
      performing assessments during inpatient rehabilitation.

PMID- 20684903
TI  - Effects of multijoint spastic reflexes of the legs during assisted bilateral hip
      oscillations in human spinal cord injury.
AB  - OBJECTIVE: To investigate the timing and magnitude of muscle activation during an
      active-assist bilateral hip motor task in human spinal cord injury (SCI). DESIGN:
      A single test session using a novel robotic system to alternately flex and extend
      the hips from 40 degrees of hip flexion to 10 degrees of hip extension at 1 of 3
      frequencies (.25, .50, .75Hz). Subjects were asked either to actively assist the
      movements or to remain relaxed during the imposed oscillations. SETTING: All data
      were collected in a research laboratory. PARTICIPANTS: Ten subjects with motor
      incomplete (American Spinal Injury Association grade C or D) SCI and 10
      individuals without neurologic injury participated in this study. INTERVENTIONS:
      Not applicable. MAIN OUTCOME MEASURES: Electromyograms and joint torques were
      recorded from the lower extremities of SCI subjects and compared with
      electromyograms and joint torque patterns recorded from 10 neurologically healthy
      individuals completing the same tasks. RESULTS: In trials involving active
      assistance of the imposed hip oscillations, SCI subjects produced muscle
      activation patterns that were phased differently from muscle activity of
      neurologically intact subjects. SCI subjects generated peak torque at the end
      ranges of movement (ie, 40 degrees hip flexion, 10 degrees extension), whereas
      control subjects generated the greatest torque midway through the movements.
      Moreover, the phasing of active-assist hip torque in SCI subjects was similar to
      the phasing of reflexive hip torques produced during the unassisted condition
      (ie, SCI subjects instructed to relax), while control subjects produced no
      reflexive torques during unassisted trials. CONCLUSIONS: The differences in the
      timing of muscle activity during the active-assist task in controls and SCI
      subjects highlights problems in generating appropriately timed muscle activity
      during ongoing movements. The similarity in muscle activity patterns for the
      active-assist and unassisted trials in SCI subjects further suggests that reflex
      feedback from hip afferents contributes substantially to muscle activation during
      active-assist movements. These findings demonstrate the disruptions in reflex
      regulation of movement in people with incomplete SCI and suggest that spastic
      reflexes might disrupt motor control.

PMID- 20684905
TI  - Validity of the fingertip-to-floor test and straight leg raising test in patients
      with acute and subacute low back pain: a comparison by sex and radicular pain.
AB  - OBJECTIVE: To use self-reported disability (Roland-Morris Disability
      Questionnaire [RMDQ]) to assess the criterion validity of straight leg raising
      (SLR) test and flexion range of motion (ROM) (fingertip-to-floor test) before and
      after stratification by sex and presence/absence of radicular pain. DESIGN: Cross
      sectional study. SETTING: Outpatient physical therapy clinic. PARTICIPANTS:
      Subjects with acute/subacute low back pain with (n=40) and without (n=35)
      radicular pain. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: We examined
      the relationship between RMDQ (reference variable) and SLR test and fingertip-to
      floor test. The sample was stratified by presence/absence of radicular pain
      (categorized by the dichotomous slump test). RESULTS: In the entire sample, fair
      correlations were found between both physical impairment tests (ie, SLR test and
      flexion ROM) and self-reported disability (.27<r>.44). After stratification by
      sex, the correlation between RMDQ and flexion ROM and between RMDQ and nonside
      specific SLR test increased in women but decreased in men. In those with
      radicular pain, good correlations were found between RMDQ and flexion ROM (r=.68
      for men and r=.70 for women), and moderate correlation was found between the RMDQ
      and SLR tests of the affected side in women (r=.60), but only fair correlation
      was found between the RMDQ and SLR tests of the affected side in men (r=.28).
      CONCLUSIONS: After stratification by sex and presence/absence of radicular pain,
      the present study supports a good validity of the fingertip-to-floor test for
      both men and women with radicular pain. The SLR test, however, was of less value
      as an indicator of self-reported disability after stratification, especially for
      men.

PMID- 20684904
TI  - Is maximal strength of the cervical flexor muscles reduced in patients with
      temporomandibular disorders?
AB  - OBJECTIVE: To determine whether there was a difference in maximal cervical flexor
      muscle strength in subjects with temporomandibular disorders (mixed and
      myogenous) compared with healthy subjects. DESIGN: Cross-sectional study.
      SETTING: Orthopedics/sports laboratory at the University of Alberta.
      PARTICIPANTS: Subjects (N=149) of whom 50 were healthy, 54 had myogenous
      temporomandibular disorders (TMD), and 45 had mixed TMD. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: Maximal cervical flexor strength, pain.
      RESULTS: There was no statistically significant difference in maximal cervical
      flexor strength among groups (P>.05). Subjects' body weight was significantly
      associated with strength. No significant association between jaw disability with
      maximal cervical flexor strength was found. A significant but weak association
      between neck disability and maximal cervical flexors strength was found.
      CONCLUSIONS: These results indicated that strength evaluation is one of several
      assessment factors that need to be addressed when evaluating musculoskeletal
      painful conditions such as TMD and neck disorders, but strength evaluation cannot
      be considered as a direct measure of disability. Future studies should explore
      evaluation of strength in other muscular groups such as cervical extensors,
      rotators, and lateral flexors, and also under different conditions such as rapid
      movements, and in patients with more severe jaw disability.

PMID- 20684906
TI  - Effects of wheelchair mass on the physiologic responses, perception of exertion,
      and performance during various simulated daily tasks.
AB  - OBJECTIVE: To verify whether additional manual wheelchair mass above a critical
      level would produce, during many daily tasks, an increase in physiologic
      parameters, an increase in the perceived exertion, and a decrease in performance.
      DESIGN: A repeated-measurement design. SETTING: Six standardized tests thought to
      mimic daily activities. PARTICIPANTS: Volunteers (N=21), 8 men with spinal cord
      injuries (SCIs; mean age, 34+/-12y; range, 19-56y) and 13 able-bodied persons (11
      men and 2 women; mean, 24+/-5y; range, 18-37y). INTERVENTIONS: Random additional
      masses ("0", 1, 2, 5kg) were placed under the seat of a multisport manual
      wheelchair (mass approximately 10kg) out of the subject's field of vision. MAIN
      OUTCOME MEASURES: Energy expenditure (EE; total o(2) consumed), heart rate (total
      number of beats), perceived exertion (visual analog scale), and performance
      (seconds to execute a sprint test) were measured. RESULTS: For all tests, there
      was no significant effect of mass found for either group for the EE, heart rate,
      and performance. In addition, for all tests, no significant effect of mass was
      found for the SCI group for the visual analog perceived exertion. However, for
      the able-bodied group, the added mass had a significant effect for the visual
      analog perceived exertion (F=6.11; P=.02) in the Stop-and-Go test. A post hoc
      Tukey test showed a significant difference between the 0kg and 5kg mass
      conditions (P<.01; d=.8), between 1kg and 5kg (P=.02; d=.6), and between 2kg and
      5kg (P=.01; d=.6). CONCLUSIONS: Based on these findings, it can be concluded
      that, under the conditions of this study, additional mass (up to 5kg) loaded on a
      multisport manual wheelchair does not seem have any effect on EE, heart rate, or
      performance and has a minor effect on the visual analog perceived exertion
      evaluated in many activities of daily living.

PMID- 20684907
TI  - Gait training with progressive external auditory cueing in persons with
      Parkinson's disease.
AB  - OBJECTIVE: To investigate the progressively increasing external auditory cues
      during mobility training with persons with Parkinson's disease (PD). DESIGN:
      Experimental. SETTING: General community. PARTICIPANTS: Convenience sample of
      persons with PD (N=12) who walked independently. INTERVENTIONS: Gait training to
      external auditory cues was based on a participant's comfortable walking pace.
      Training external auditory cues rates were increased if patients were able to
      maintain or increase stride length with increasing external auditory cues rate.
      Movement synchronization was not monitored during training. Participants trained
      for 30min/session, 3 sessions/wk, for 8 weeks. MAIN OUTCOME MEASURES: Walking
      velocity, stride length, and cadence. RESULTS: Participants trained at a mean
      maximal rate of 157bpm. They showed a significant (P<.01) increase in walking
      velocity, stride length, and cadence after 8 weeks of training. CONCLUSIONS:
      Walking velocity, stride length, and cadence can significantly improve when
      community-dwelling persons with PD participate in progressive mobility training.

PMID- 20684908
TI  - Longitudinal changes in physical capacity over 20 years in athletes with spinal
      cord injury.
AB  - OBJECTIVE: To investigate the longitudinal changes in physical capacity over 20
      years in athletes with spinal cord injury (SCI). DESIGN: Longitudinal study (20-y
      follow-up). SETTING: Laboratory setting. PARTICIPANTS: Persons with SCI (N=7).
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Maximum oxygen consumption
      Vo(2)max) measured in 1986-1988 and in 2006. RESULTS: Subjects with SCI
      maintained stable Vo(2)max in 2006. Six of the 7 continued various wheelchair
      sports activities, while 1 person quit sports activities 1 year after the
      baseline study. The latter person showed reduced Vo(2)max by 53%, while 2 persons
      who continued strenuous wheelchair sports activities showed increased Vo(2)max by
      43% and 45% after 20 years. CONCLUSION: The results indicated that physical
      capacity reflected the level of sports activity in subjects with SCI who
      maintained sports activities.

PMID- 20684909
TI  - Talar positional fault in persons with chronic ankle instability.
AB  - OBJECTIVE: To determine whether sagittal plane talar position differs between
      uninjured controls and individuals with chronic ankle instability (CAI) using
      lateral ankle radiographs. DESIGN: Single-blind case control. SETTING: University
      based sports medicine research laboratory. PARTICIPANTS: University students
      (N=48) volunteered to participate. Twenty-four uninjured controls (12 men, 12
      women; mean +/- SD, 21.8+/-2.6y; 170+/-10cm; 73+/-16kg), and 24 adults with CAI
      (12 men, 12 women; 21.7+/-2.8y; 175+/-13cm; 71+/-13kg) participated.
      INTERVENTION: A single nonweight-bearing lateral radiograph was taken of each
      ankle. Subjects were positioned side lying with the hip and knee in a neutral
      position in the transverse plane and the ankle joint in a neutral position (90
      degrees of dorsiflexion, 0 degrees of inversion/eversion). MAIN OUTCOME MEASURE:
      The sagittal plane talar position was calculated as the distance between the most
      anterior margin of the inferior tibia and the most anterior margin of the talar
      dome in millimeters for each radiograph. RESULTS: Talar position was
      significantly more anterior in the involved CAI limb (3.69+/-1.37mm) than the
      uninvolved CAI limb (2.98+/-1.61mm; P=.03). Additionally, an anterior talar
      position was significantly greater in the involved CAI limb than the matched
      control limb (2.65+/-1.24cm; P<.01). No differences were found between the
      uninvolved CAI limb and the matched control group limb (P=.57) or between the
      limbs of the uninjured control group (P=.75). Intratester reliability was found
      to be .90, while intertester reliability was .78. CONCLUSIONS: An anterior talar
      positional fault is present in the involved limb of individuals with CAI relative
      to their uninvolved limb and compared with the matched limb of a control group.
      The talar position measurement technique has excellent intratester and
      intertester reliability.

PMID- 20684910
TI  - Detection of gait and postures using a miniaturized triaxial accelerometer-based
      system: accuracy in patients with mild to moderate Parkinson's disease.
AB  - OBJECTIVE: To examine whether gait and postures can accurately be detected with a
      single small body-fixed device in patients with mild to moderate Parkinson's
      disease (PD). DESIGN: Results of a triaxial accelerometer-based method were
      evaluated against video observation scores (criterion measure). Study 1: Subjects
      performed basic mobility-related activities (walking, lying, sitting, standing)
      in a fixed and free sequence. Study 2: Subjects were monitored while doing
      similar activities as in study 1 and while doing usual domestic activities.
      SETTING: Study 1: Standardized set-up in a movement laboratory. Study 2: Home
      environment. PARTICIPANTS: (N=37) Study 1: Patients with PD (n=32; mean age +/-
      SD, 67.3+/-6.6y; mean disease duration +/- SD, 6.1+/-3.4y). Study 2: Patients
      with PD (n=5; mean age +/- SD, 76.0+/-7.3y; mean disease duration +/- SD, 3.8+/
      4.7y). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The degree of
      correspondence between the monitor and the video observation for the duration of
      each activity. Overall agreement, sensitivity, specificity, and positive
      predictive values were calculated. RESULTS: Study 1: Overall agreement ranged
      between 69.8% and 90.8% (fixed sequence) and 57.5% and 96.9% (free sequence).
      Study 2: Overall agreement ranged between 60.0% and 89.2%. Lying, sitting (home),
      and walking were detected most accurately with mean sensitivity varying from
      81.7% to 99.9%. Lower values were found for sitting (laboratory), standing, and
      shuffling. CONCLUSIONS: This triaxial monitor system is a practical and valuable
      tool for objective, continuous evaluation of walking and postures in patients
      with mild to moderate PD. Detection of sitting and standing requires further fine
      tuning.

PMID- 20684911
TI  - A preliminary report on the efficacy of a dynamic jaw opening device (dynasplint
      trismus system) as part of the multimodal treatment of trismus in patients with
      head and neck cancer.
AB  - OBJECTIVE: To examine the effectiveness of a dynamic jaw opening device as part
      of a multimodal treatment strategy for trismus in patients with head and neck
      cancer. DESIGN: Retrospective cohort study. SETTING: Tertiary care cancer center.
      PARTICIPANTS: Patients with head and neck cancer and trismus (N=20).
      INTERVENTION: All patients underwent assessment by a board-certified physiatrist
      and were referred to physical therapy for delivery of the DTS and instructed to
      progress use of the DTS to 30 minutes 3 times a day. Additional modalities for
      the treatment of trismus including pain medications and botulinum toxin
      injections were prescribed as clinically indicated. MAIN OUTCOME MEASURES: Change
      in maximal interincisal distance (MID) as documented in the medical record.
      RESULTS: The use of the DTS as part of multimodal therapy including physical
      therapy, pain medications, and botulinum toxin injections as deemed clinically
      appropriate resulted in an overall improvement of the MID from 16.5mm to 23.5mm
      (P<.001). Patients who could comply with the treatment recommendations for DTS
      treatment did better than those who could not, with an improvement of the MID
      from 16 mm to 27 mm (P<.001) versus 17 mm to 22 mm (P=.88). CONCLUSIONS: The DTS
      is a safe and effective component of a multimodal strategy for improving trismus
      associated with head and neck cancer and its treatment. Further investigation is
      needed to determine the relative efficacy of the treatment modalities available
      for trismus including physical therapy and other jaw stretching devices.

PMID- 20684912
TI  - Physical activity measurement using MTI (actigraph) among children with cerebral
      palsy.
AB  - OBJECTIVE: To investigate the validity of MTI accelerometer as a physical
      activity (PA) measurement instrument for children with cerebral palsy (CP).
      DESIGN: Participants were classified within Gross Motor Function Classification
      System I to III and took part in 2 activity sessions: (1) a structured activity
      protocol with increasing intensities and (2) a free play session. Concurrent
      measurements of activity counts, heart rate, and observed physical activity were
      performed. SETTING: Data were collected on normal school days in special schools
      within the participants' 30-minute break period. PARTICIPANTS: Convenience sample
      of children with CP (N=31; 17 girls, 14 boys) age between 6 and 14 years (mean +/
      SD, 9.71+/-2.52 y). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: MTI
      measured activity counts, a monitoring device measured heart rate, and the System
      for Observing Fitness Instruction Time (SOFIT) was used for direct PA
      observation. RESULTS: There were strong relationships between MTI and SOFIT
      (r=.75; R(2)=.56; P<.001) and heart rate monitor (HRM) and SOFIT (r=.65;
      R(2)=.43; P<.001) data in structured activities, but the difference between these
      2 correlation coefficients was not significant (P=.46). In free play activities,
      the association between MTI and SOFIT data (r=.67; R(2)=.45; P<.001) was
      significantly stronger (P=.01) than that between heart rate and SOFIT data
      (r=.14; R(2)=.02; P<.001) . Bland-Altman plots showed better agreement between
      observed SOFIT and MTI-predicted SOFIT data than observed SOFIT and HRM-predicted
      SOFIT data from the linear regression analysis. CONCLUSIONS: The findings suggest
      that the MTI appears to be a valid instrument for measuring raw activity volume
      among children with CP and is suitable for use in studies attempting to
      characterize the PA of this population.

PMID- 20684913
TI  - Evidence on the effectiveness of topical nitroglycerin in the treatment of
      tendinopathies: a systematic review and meta-analysis.
AB  - OBJECTIVE: To evaluate evidence on the effectiveness of topical nitroglycerin
      (NTG) in treating tendinopathies. DATA SOURCES: Systematic searches were
      conducted on ScienceDirect, Scirus, Highwire Press Stanford University, PubMed
      Central, Directory of Open Access Journals, Free Medical Journals, Free Full
      Text, Bioline International, Findarticles, BioMed Central, IndMed, OpenMD, QMed,
      Geneva Foundation for Medical Education and Research, Scientific Electronic
      Library Online, eMedicine/Medscape/Medline, Biomedical E-journals, Current
      Contents Connect, Journal of Medical Internet Research, Cochrane, Turning
      Research Into Practice, Ovid, and EBSCO databases. There were no restrictions
      regarding the language of publication. STUDY SELECTION: All clinical controlled
      trials or randomized controlled trials (RCTs) evaluating the effects of NTG for
      patients with acute, subacute, or chronic tendinopathies, whether the said
      intervention was placebo-controlled or controlled against a comparator
      intervention, were considered for inclusion. DATA EXTRACTION: A reviewer
      extracted data from included studies using a data extraction form by the Joanna
      Briggs Institute. DATA SYNTHESIS: Methodologic quality of studies was assessed by
      2 independent reviewers through a critical appraisal form by the Alberta Heritage
      Foundation. Qualitative analyses of data were done using a rating system devised
      by Van Tulder and colleagues. Where possible, meta-analyses of data were
      performed. Seven clinically relevant and high-quality RCTs involving 446 subjects
      were identified and included in this review. Meta-analysis showed that NTG has a
      positive effect in pain reduction during activities of daily living in chronic
      tendinopathies, with an odds ratio of 4.44 (95% confidence interval [CI], 2.34
      8.40), and in both acute and chronic phases combined, with an odds ratio of 4.86
      (95% CI, 2.62-9.02). There is also qualitative, strong (Level 1) evidence that
      NTG is effective in enhancing tendon forces in the chronic phase. There is
      limited and/or conflicting evidence (Level 3) for other outcomes in the chronic
      phase and all outcomes in the acute phase. There is a significant between-group
      difference between NTG and control in the incidence of headache, with an odds
      ratio of 1.73 (95% CI, 1.01-2.97). No significant difference was observed in the
      occurrence of contact dermatitis, with an odds ratio of 2.12 (95% CI, .89-5.02).
      CONCLUSIONS: In chronic tendinopathies, there is strong evidence for NTG in
      relieving pain during activities of daily living, and increasing tendon strength.
      Further studies are needed to explore the role of this promising intervention in
      all phases of tendinopathies.

PMID- 20684914
TI  - Invited commentary on "Discrimination of real and sham acupuncture needles using
      the park sham device: a preliminary study".
AB  - Peter T. Dorsher, MS, MD, provides an interesting commentary on the findings of a
      study by Tan and colleagues that was highlighted in the December issue of the
      Archives as displaying potential deficiencies in a number of sham acupuncture
      devices. Dr. Dorsher's comments, while focused on acupuncture, are interesting in
      their own right. However, a little thought shows that his insights into the
      nature of an adequate placebo provide an improved understanding of the issues
      involved in the design and validation of control interventions in general.

PMID- 20684916
TI  - Trauma symptoms inventory scale, return to work, and atypical complex regional
      pain syndrome type 1?

PMID- 20684917
TI  - Measurement of the environment of people with disabilities.

PMID- 20684921
TI  - The journal of "handy" surgery.

PMID- 20684920
TI  - New paradigms in the management of diverticular disease.

PMID- 20684922
TI  - Incidence estimates and demographics of scaphoid fracture in the U.S. population.
AB  - PURPOSE: The epidemiology of scaphoid fracture is based mostly on retrospective
      analyses of small population centers. The purpose of this study was to determine
      the incidence of scaphoid fractures in a large national population database.
      METHODS: The National Electronic Injury Surveillance System (NEISS) is a
      representative sample of patients that is weighted to provide estimates of
      various injuries in the United States presenting to emergency rooms. Data on
      wrist fractures obtained from NEISS were used to estimate the incidence of
      scaphoid fractures in the United States between 2002 and 2006. We could not
      distinguish true scaphoid fractures from suspected scaphoid fractures.
      Demographics, location, mechanism, and sports participation were also recorded.
      RESULTS: A total of 507 injuries coded as fractures of the scaphoid were
      identified in the database from 2002 to 2006. According to the methodology of the
      NEISS sample, this corresponds to an estimated 21,481 scaphoid fractures among
      909,309 total wrist fractures nationwide (2.4%) and an estimated incidence of
      scaphoid fractures of 1.47 fractures per 100,000 person-years (95% confidence
      interval, 1.31-1.63). CONCLUSIONS: The estimated incidence of scaphoid fractures
      using U.S. census data is an order of magnitude less than the estimates in prior
      studies. If the data represent both suspected and true fractures, the incidence
      of true scaphoid fractures is likely an order of magnitude less than our
      estimates. Young males and persons between 10 and 19 years of age are at highest
      risk for scaphoid fracture.

PMID- 20684923
TI  - Optimal fixation of acute scaphoid fractures: finite element analysis.
AB  - PURPOSE: The hypothesis of this study was that more stable fixation of acute
      scaphoid fractures may be achieved by a screw placed perpendicular to the
      fracture plane than along the long axis of the scaphoid, as previously suggested.
      We examined this assumption on different fracture patterns using a finite element
      analysis model. METHODS: A computed tomography scan of an intact scaphoid of a
      young man provided the data set for all fracture models. We used semiautomatic
      segmentation to create 3-dimensional computer models of the 3 simple fracture
      configurations: oblique, transverse waist, and proximal fractures, according to
      the Herbert classification. Each fracture type was analyzed, using finite
      elements, for its biomechanical response to 2 types of virtual fixation: a screw
      placed either perpendicular to the fracture plane or centrally along the long
      axis of the scaphoid. We measured motion at the fracture plane (in millimeters)
      and strain in the screw threads (in millipascals). RESULTS: Considerably less
      motion was measured at the fracture plane with the perpendicular screw compared
      with the long axis screw, especially in the oblique-type fractures: (1) Herbert
      type B1 oblique fracture mean motion of 0.05 mm (+/-0.03) for the perpendicular
      screw versus 0.28 mm (+/-0.05) for the long axis screw; (2) B2 transverse waist
      fracture mean motion of 0.06 mm (+/-0.03) for the perpendicular screw versus 0.18
      mm (+/-0.06) for the long axis screw; and (3) B3 proximal fracture mean motion of
      0.07 mm (+/-0.01) for the perpendicular screw versus 0.28 mm (+/-0.011) for the
      long axis screw. Higher strains were measured on the screw placed perpendicular
      to the fracture. CONCLUSIONS: According to this model, higher fixation stability
      is achieved when the scaphoid is fixated perpendicular to the fracture. In
      transverse waist fractures, a centrally placed screw will also be perpendicular
      to the fracture, which explains the results of previous models.

PMID- 20684924
TI  - Triangular fibrocartilage complex tears associated with symptomatic ulnar styloid
      nonunions.
AB  - PURPOSE: Tear of the triangular fibrocartilage complex (TFCC) and nonunion of the
      ulnar styloid are common lesions resulting from upper extremity injuries such as
      distal radius fractures. Whereas ulnar styloid fractures are a common feature of
      the distal radius fracture pattern, symptomatic nonunions of the ulnar styloid
      are found in a minority of these injuries. The purposes of this study were to
      confirm the association of symptomatic ulnar styloid nonunions and TFCC tears,
      and to report intra-articular findings and clinical outcomes for the concurrent
      arthroscopic management of TFCC tears and open excision of ulnar styloid
      nonunions in a consecutive series of patients. METHODS: We retrospectively
      reviewed the medical records of 8 consecutive patients who underwent open
      excision of an ipsilateral ulnar styloid nonunion fragment and concurrent
      diagnostic arthroscopy. The diagnosis of TFCC tear was made by magnetic resonance
      imaging preoperatively in only 5 of 8 patients. We assessed outcomes with the
      Disabilities of the Arm, Shoulder, and Hand questionnaire and the visual analog
      scale. RESULTS: Arthroscopic findings demonstrated full-thickness chondral injury
      on the dorsum of the triquetrum with a tear of the dorsal radiolunotriquetral
      ligament and avulsion of the ulnar margin of the TFCC from the extensor carpi
      ulnaris subsheath. The clinical outcome scores showed statistically significant
      improvement (p<.05) from the preoperative baseline, with a mean Disabilities of
      the Arm, Shoulder, and Hand score of 3.69 (SD, 9.68) and a mean visual analog
      scale pain score of 1.0 (SD, 0.83) postoperatively. CONCLUSIONS: Symptomatic
      ulnar styloid nonunions can be associated with TFCC tears, and diagnostic
      arthroscopy should be considered in all patients who are candidates for open
      excision of an ulnar styloid nonunion. Concurrent arthroscopic TFCC repair and
      open excision of the ulnar styloid fragment is an effective surgical approach for
      this combined injury pattern.

PMID- 20684925
TI  - Ring and little finger metacarpal fractures: mechanisms, locations, and
      radiographic parameters.
AB  - PURPOSE: To describe a series of ring and little finger metacarpal fractures with
      regard to mechanism, location, midshaft diameter, and isthmus diameter, to better
      define injury patterns and assist the surgeon in selection of appropriately sized
      implants. METHODS: We reviewed all metacarpal fractures in skeletally mature
      patients who presented to a single surgeon over a 2-year period. Fractures of the
      ring and little finger metacarpals were analyzed with regard to mechanism and
      fracture location. Metacarpal midshaft and minimum isthmus diameters were
      measured on posteroanterior radiographs. RESULTS: A total of 101 fractures
      involved the ring and little finger metacarpals. Punching-type injuries accounted
      for most fractures in the little finger metacarpal (49 of 67) and ring finger
      metacarpal (26 of 34). Among these punching-related ring and little finger
      metacarpal fractures, the most common fracture location was the little finger
      metacarpal neck (34 of 75), followed by the ring finger metacarpal shaft (21 of
      75). Among men in this series, the metacarpal midshaft and minimum isthmus
      diameters were significantly narrower in the ring finger metacarpal than in the
      little finger (7.4 vs 8.7 mm, p < .001; and 2.2 vs 3.8 mm, p < .001).
      CONCLUSIONS: Whereas punching injuries tended to cause neck fractures in little
      finger metacarpals in this series, they caused shaft fractures in ring finger
      metacarpals, which may thus be considered a variant boxer's fracture.
      Furthermore, in men with fractures, the ring finger metacarpal is significantly
      narrower than the little finger, both in midshaft diameter and isthmus diameter,
      which surgeons should consider when planning internal fixation. TYPE OF
      STUDY/LEVEL OF EVIDENCE: Prognostic IV.

PMID- 20684926
TI  - Osteochondral mosaicplasty as a treatment method for bilateral avascular necrosis
      of the long finger metacarpal: case report.
AB  - Avascular necrosis of the metacarpal head is a rare condition known to occur in
      conjunction with repetitive trauma, systemic lupus erythematosus, and the use of
      steroids. This clinical case reports a 31-year-old man with bilateral long finger
      metacarpal head avascular necrosis, treated with osteochondral mosaicplasty.

PMID- 20684927
TI  - Nonunion and avascular necrosis following phalangeal neck fractures in children.
AB  - PURPOSE: To investigate the characteristics of nonunion and avascular necrosis
      following phalangeal neck fracture in children. METHODS: A cohort of all
      pediatric phalangeal neck fractures complicated by nonunion, with or without
      avascular necrosis of the phalangeal head, over the last 10 years was reviewed
      retrospectively. The following data were documented: age, gender, fracture site,
      mechanism of injury, fracture type, presence of digital ischemia, initial
      management, and outcome. RESULTS: Our database of phalangeal neck fractures in
      children over the last 10 years included 215 fractured digits. Of these, 4
      developed nonunion (group A) and 8 developed nonunion with avascular necrosis
      (group B). All patients in group A were young children (mean age, 2.5 y) with
      fractured thumbs, initially managed by closed reduction and splinting. The
      fractures redisplaced and failed to unite, resulting in instability that was
      later treated by bone grafting and stabilization with a K-wire. Patients in group
      B were older children (mean age, 5.6 y) and 7 of 8 had finger fractures. All 8
      patients presented with stiffness of the affected joint, and no further surgery
      was performed. CONCLUSIONS: When nonunion occurs following pediatric phalangeal
      neck fractures, it usually affects the thumb and presents with thumb instability,
      and bone grafting is often required to achieve union. In contrast, avascular
      necrosis following phalangeal neck fractures usually affects the little finger
      and presents with stiffness, and hence, further surgery is not often required
      short term, although the long-term result after skeletal maturity is unknown.
      TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 20684928
TI  - Interphalangeal traction for comminuted fracture of middle phalanx fingers: case
      report.
AB  - We report an interphalangeal traction system through capsuloligamentotaxis for
      the treatment of comminuted fracture of the middle phalanx. The interphalangeal
      (IP) traction system inserts a K-wire at the proximal and distal phalanx. The
      difference between our IP traction system compared with the modified Suzuki frame
      method is that distal IP and proximal IP joints are synchronously distracted in
      the fixator, and bony continuity and articular integrity are restored.

PMID- 20684929
TI  - Efficacy of median nerve recurrent branch neurectomy as an adjunct to ulnar motor
      nerve neurectomy and wrist arthrodesis at the time of superficialis to profundus
      transfer in prevention of intrinsic spastic thumb-in-palm deformity.
AB  - PURPOSE: The superficialis to profundus (STP) tendon transfer is an effective
      procedure to correct a spastic clenched fist deformity in a nonfunctional upper
      extremity. An intrinsic thumb-in-palm (TIP) deformity, caused by increased
      activity in the adductor pollicis and flexor pollicis brevis muscles, commonly
      becomes apparent after an STP procedure. The goal of this study was to
      investigate the efficacy of median nerve recurrent branch neurectomy, done at the
      time of STP and in concert with an ulnar motor nerve neurectomy and wrist
      arthrodesis, in the prevention of an intrinsic TIP deformity caused by spastic
      thenar muscles. METHODS: We retrospectively evaluated a consecutive series of 23
      patients with upper motor neuron syndrome who underwent an STP transfer performed
      by a single surgeon at our institution. Group 1 included 11 consecutive patients
      who underwent an STP, ulnar nerve motor branch neurectomy, and wrist arthrodesis.
      Group 2 included 12 consecutive patients who underwent the same procedures with
      the addition of a neurectomy of the recurrent median nerve. We examined outcomes
      including development of a postoperative intrinsic TIP deformity, resolution of
      hygiene issues, and the need for additional surgery to correct the remaining
      deformities. RESULTS: Patients were observed for an average of 16.1 months. In
      group 1, 5 of 11 patients developed an intrinsic TIP deformity, compared with 2
      of 12 in group 2. Hygiene-related issues resolved in 8 of 11 patients in group 1
      and 10 of 12 patients in group 2. There were no wound infections. In the 7
      patients with postoperative intrinsic TIP deformity (5 in group 1 and 2 in group
      2), 5 elected to have additional surgery. Of the 7 patients, 2 declined
      additional surgery because their deformities were mild and their hygiene issues
      had resolved. CONCLUSIONS: Median nerve recurrent branch neurectomy appears to be
      a useful adjunct to STP with ulnar motor branch neurectomy and wrist arthrodesis
      in the prevention of an intrinsic TIP deformity in the nonfunctional hand. TYPE
      OF STUDY/LEVEL OF EVIDENCE: Therapeutic III.

PMID- 20684930
TI  - Painful snapping elbow in patients with congenital radioulnar synostosis: report
      of two cases.
AB  - Two patients with congenital radioulnar synostosis presented with painful
      snapping on elbow motion in one case and locking of the elbow joint in the other.
      Elbow arthroscopy revealed the presence of tight fibrous tissue trapping the
      radial head. Arthroscopic removal of this tight fibrous tissue resulted in
      painless joint motion without recurrence of snapping or locking.

PMID- 20684931
TI  - Osteochondroma associated with complete rupture of the distal biceps tendon: case
      report.
AB  - Osteochondromas are the most common benign bone tumors. However, osteochondromas
      rarely involve the proximal radius. We present the case of a solitary
      osteochondroma that occurred in a critical area of the proximal radius near the
      insertion of the biceps tendon and ultimately led to rupture of the tendon. The
      lesion was confirmed histologically and resected, followed by successful repair
      of the distal biceps tendon using a suture anchor.

PMID- 20684932
TI  - Evidence-based medicine: disproportionate pain and disability.

PMID- 20684933
TI  - Open fractures of the distal radius.

PMID- 20684934
TI  - Fascial flaps for hand reconstruction.
AB  - Free or pedicled fascial flaps to the hand provide an excellent reconstructive
      option in cases of exposed tendon, joint, or bone where soft tissue coverage is
      needed. They provide thin, broad, well-vascularized coverage and a gliding
      surface for tendons and joints. A fascial flap also avoids an unsightly donor
      site that results from a fasciocutaneous flap. Because of these characteristics,
      mobilization can be started early to avoid or minimize tendon adhesions and joint
      and soft tissue contractures. In this report, we discuss the technique for
      harvesting and insetting a pedicled reverse radial forearm adipofascial flap for
      a dorsal thumb defect.

PMID- 20684935
TI  - Refinements in dorsoulnar flap of the thumb: 15 cases.
AB  - PURPOSE: We report 2 modifications of the classic Brunelli flap to avoid vascular
      compromise and first web contracture, common when using medium or large flaps.
      METHODS: We treated 15 patients with posttraumatic loss of palmar surface and
      distal amputation of the thumb, with dorsoulnar flap associated with 2
      refinements. The first technical tip was an adipofascial extension proximal in
      the flap aimed to decrease the morbidity of the donor site without changing the
      potential covering of the flap. The second was always to graft the pedicle of the
      flap, avoid vascular compression problems, and moreover, to use the pedicle to
      cover the traumatic area. All ulnar dorsal digital nerves of the flaps were
      reconnected to one of the volar digital nerves. The minimum patient follow-up was
      12 months. RESULTS: All flaps achieved primary healing without major
      complications. There were no donor site problems. Cosmetic debulking of the flap
      over the pedicle has not been required. CONCLUSIONS: The Brunelli flap is a good
      technique to cover small and moderate defects of the thumb, although the drawback
      of this procedure is the lack of sensory recovery. The refinements of this series
      can help to improve the use of this flap and avoid complications in the donor
      site.

PMID- 20684936
TI  - Update of the physiology and biomechanics of tendon transfer surgery.
AB  - Tendon transfer surgery has evolved over the past decade. Unique muscle
      properties have been elucidated in terms of potential force generation,
      excursion, and metabolic properties. The choice of an appropriate donor muscle is
      becoming more of a science than an art. The measurement of sarcomere length has
      progressed from the laboratory into surgery. Methods of tendon coaptation have
      advanced to allow early mobilization. This article reviews recent advances in our
      understanding of tendon transfer surgery of the hand and upper extremity.

PMID- 20684937
TI  - Update on tendon transfers for peripheral nerve injuries.
AB  - Tendon transfer surgery to restore fundamental wrist and hand function is made
      possible by the redundancy that exists among the actions of our upper-extremity
      musculature. Potential donors for transfer are those muscles with adequate power
      to motor the recipient tendon, similar tendon excursion to the recipient, and
      function in phase with the recipient. Resolution of wound healing, union of
      fractures, and mobilization of stiff joints are prerequisites for a functioning
      tendon transfer. Injuries to the radial, median, and ulnar nerves occur above
      (high nerve injury) and below the elbow (low nerve injury). High and low nerve
      injuries result in different functional deficits that require unique tendon
      transfers to enhance function. This report discusses the various tendon transfers
      necessary to overcome deficits resulting from high and low radial, median, and
      nerve injuries.

PMID- 20684938
TI  - [Complications of endoscopic sinus surgery in a residency training program].
AB  - INTRODUCTION: Endoscopic sinus surgery presents a series of complications that
      can vary depending on the technique used and the surgeon's experience. This
      technique needs a learning curve, which must be developed during the residence
      training program. METHODS: Descriptive and retrospective study, reviewing the
      medical records of endoscopic sinus surgery for nasal polyps of 192 patients who
      had undergone operations performed by residents at our department between January
      2002 and January 2008. Patient sex, age, affectation scale and minor and major
      complications were described. All these procedures were performed by 3rd or 4th
      year residents under the supervision of a faculty member. RESULTS: Of the 192
      patients, 127 (66.14%) were male and 65 (33.85%) female, aged between 24 and 78
      years old, with a mean age of 49 years old. Nasal endoscopy revealed polyposis of
      grade i, 19 (9.8%) cases; grade ii, 55 (28.6%); and grade iii, 118 (61.45%).
      There were 44 (22.9%) total complications, 40 (20.8%) minor and 4 (2.08%) major
      complications. The most common minor complication was synechia formation in
      21(10.93%) cases, followed by bleeding without need for transfusion in 12
      (6.25%). The major complication was a breach of the lamina papyracea in 4
      patients (2.08%). There were no cases of blindness, cerebrospinal fluid
      rhinorrhea, or death. CONCLUSIONS: Endoscopic sinus surgery in an otolaryngology
      residency training program is a relatively safe procedure, especially when
      performed under faculty supervision.

PMID- 20684939
TI  - [Primary malignant solitary fibrous tumor/hemangiopericytoma of the parotid
      gland].
AB  - Solitary fibrous tumor (SFT) was first described in the pleura by Lietaud in
      1767; later in 1870, Wagner described the localized nature of this type of tumor
      and Klemperer and Rabin classified pleural tumors into two types: diffuse
      mesotheliomas and localized mesotheliomas. Recent years have seen the
      redefinition of this neoplasm, due to better technology; it is now proven that
      this neoplasm may have multiple different extrapleural origins including the head
      and neck regions. This diversity of locations is related to the particular
      mesenchymal histogenesis of SFT which allows its development from very unusual
      sites such as the salivary glands (SGs). In this particular site, this neoplasm
      is very infrequent and most of reported cases refer to benign disease, with just
      one case informed so far of primary malignant SFT.

PMID- 20684940
TI  - [The current role of partial surgery as a strategy for functional preservation in
      laryngeal carcinoma].
AB  - With the current advances and recent organ preservation protocols for
      intermediate or advanced stage laryngeal cancer, based on chemotherapy, the role
      of surgery seemed replaced except for surgical rescue of tumours not responding
      to these treatments, total laryngectomy being the surgical option. This type of
      non-surgical treatment is offered as a strategy for organ preservation, as
      opposed to total laryngectomy. However, we believe that there are two organ
      preservation strategies, surgical and non-surgical. A wide spectrum of surgical
      techniques is available and such techniques lead to excellent results, both
      oncological and functional (speech and swallowing). The aim of this paper is to
      present options for organ-preserving surgery for laryngeal cancer. A review of
      surgical techniques available for functional preservation in cancer of the larynx
      at intermediate or advanced stage is presented. In addition to classic approaches
      such as vertical partial laryngectomy and horizontal or supraglottic
      laryngectomy, options for conservative laryngeal surgery have improved
      significantly over the past two decades. Minimally invasive surgery, transoral
      laser surgery, and supracricoid partial laryngectomy have become important
      laryngeal preservation approaches for patients with laryngeal cancer. Surgery
      must define its role in the multidisciplinary treatment of advanced cancers of
      the larynx, which at present often favours (chemo)radiotherapy protocols.

PMID- 20684941
TI  - Cognitive underpinnings of contextual interference during motor learning.
AB  - The reported study examined the cognitive processes underlying contextual
      interference (CI) in motor learning. This experiment was designed to assess the
      combined influence of practice schedule (blocked or random) and task similarity
      (similar or dissimilar) on acquisition and retention performance. Participants
      (N=60) learned a set of three variations of a timing task according to a similar
      (900, 1000 and 1100ms) or dissimilar parameter condition (700, 1000 and 1300ms)
      with either a blocked or random practice order: this resulted in 4 experimental
      groups. Performance in delayed retention demonstrated a typical CI effect due to
      the schedule of practice for the dissimilar parameter condition with the random
      practice group outperforming the blocked practice group. Conversely, no blocked
      random difference was found for the similar parameter condition. These findings
      lend support for the reconstruction hypothesis by showing that supplementing
      random practice with additional intertask elaboration (i.e., similar parameter
      condition) did not facilitate subsequent retention performance.

PMID- 20684942
TI  - Platelet reactivity and pregnancy loss.
AB  - OBJECTIVE: We sought to critically evaluate platelet function in recurrent
      miscarriage (RM). STUDY DESIGN: We conducted a prospective study comparing 30
      patients with unexplained recurrent first-trimester pregnancy loss with 30
      control subjects matched for age and serum progesterone level. Platelet function
      was determined using a modified assay of light transmission aggregometry with
      multiple agonists at different concentrations. Dose-response curves were created
      and half-maximal effective concentration values were calculated. RESULTS: At test
      completion the half-maximal effective concentration values for arachidonic acid
      in the patients with RM were significantly less than in the control subjects
      (0.153 vs 0.230; P = .0099). The dose-response curves were tightly matched for
      the other agonists. CONCLUSION: This novel measurement of platelet function has
      demonstrated that patients with unexplained RM have significantly increased
      platelet aggregation in response to arachidonic acid. The enhanced response to
      this agonist provides an empirical rationale for the use of aspirin in management
      of this clinical condition.

PMID- 20684943
TI  - Longitudinal assessment of bone loss from diagnostic computed tomography scans in
      gynecologic cancer patients treated with chemotherapy and radiation.
AB  - OBJECTIVE: The objective of the study was to measure the volumetric bone mineral
      density (vBMD) using diagnostic computed tomography scans in gynecologic oncology
      patients. STUDY DESIGN: In a retrospective study, spine and femoral neck (FN)
      vBMD was measured for 1 year in 40 patients receiving chemotherapy or radiation.
      RESULTS: There is significant bone loss after chemotherapy, radiation, and a
      combination of radiation and chemotherapy (P = .0211). In 1 year, the percent
      reduction in vBMD (+/-SE) at L1-L2 spine and the FN was a 15.9% (+/-5.67) and
      10.4% (+/-4.06) in chemotherapy; 11% (+/-5.68) and 15.8% (+/-2.56) in radiation;
      and 21.0% (+/-7.03) and 3.6% (+/-3.3.7) in the combined therapy group. Bone loss
      was evident immediately after treatment and persisted or worsened in most women.
      CONCLUSION: Gynecologic cancer patients treated with chemotherapy or radiation
      experience immediate and prolonged bone loss; thus, pre- and posttreatment
      monitoring of bone loss is important in these patients.

PMID- 20684944
TI  - Lipoxygenase and cyclooxygenase inhibitors reveal a complementary role of
      arachidonic acid derivatives in pregnant human myometrium.
AB  - OBJECTIVE: The aim of this study was to assess the involvement of lipoxygenase
      (LOX) metabolic pathways in uterine tissues from pregnant women as well as the
      combined inhibition of LOX and cyclooxygenase (COX) on contractile activity.
      STUDY DESIGN: Uterine biopsies were performed from consenting women undergoing
      elective caesarean sections at term (n = 24). Western blot analysis and isometric
      tension measurements were performed in vitro on fresh human myometrial strips.
      Concentration-response curves to arachidonic acid (AA) 861 and baicalein (5- and
      12-LOX inhibitors, respectively) were performed. The combined effects of
      baicalein and indomethacin were also assessed. Contractile activities were
      quantified by calculating both amplitude and the area under the curve over 20
      minute periods. RESULTS: 5- and 12-LOX were present in all tested tissues.
      Addition of AA861 or baicalein resulted in tocolytic effects (P < .05). Finally,
      the combined inhibition of both COX and 12-LOX pathways resulted in additive
      tocolytic effects. CONCLUSION: 5- and 12-LOX pathways modulate human myometrium
      contractility.

PMID- 20684945
TI  - The mechanical PR interval in fetuses of women with intrahepatic cholestasis of
      pregnancy.
AB  - OBJECTIVE: The purpose of this study was to evaluate the fetal mechanical PR
      interval in intrahepatic cholestasis of pregnancy (ICP). STUDY DESIGN: Fetal
      echocardiography was performed for women with ICP and control subjects. Clinical
      characteristics, total bile acids, and liver profile tests were compared between
      groups. RESULTS: Fourteen women with ICP and 7 control subjects were enrolled.
      Total bile acids (28.3 vs 6.2 MUmol/L; P < .001), aspartate aminotransferase (53
      vs 23 IU/L; P = .002), alanine aminotransferase (63 vs 19 IU/L; P = .002), and
      the PR interval (124 vs 110 msec; P = .006) were significantly higher in fetuses
      with ICP than in control fetuses. On multivariable linear regression analysis,
      only the presence of ICP was associated significantly with an increase in the PR
      interval (95% confidence interval, 4-24 msec; P = .01). CONCLUSION: The fetal
      cardiac conduction system is altered in ICP. Further investigation is needed to
      determine whether fetal echocardiography can help to predict which fetuses are at
      risk for death that is associated with ICP.

PMID- 20684946
TI  - Venous Doppler studies in low-output and high-output hydrops fetalis.
AB  - OBJECTIVE: The objective of the study was to compare fetal venous Doppler flow
      reflecting cardiac function in fetuses with hydrops fetalis between a group of
      congenital heart defect (low cardiac output) and a fetal anemia group (high
      cardiac output). STUDY DESIGN: This was a prospective cross-sectional analysis.
      It was conducted at the Maharaj Nakorn Chiang Mai Hospital, Tertiary center,
      Medical School. The study included fetuses with hydrops fetalis secondary to
      cardiac causes (low output group) and anemia (high output group). All fetuses
      underwent ultrasound examination to assess ductus venosus (DV) and umbilical vein
      (UV) Doppler indices. The results were related to normal reference range and were
      also compared between the group of high-output and the low-output group. RESULTS:
      Sixty-nine hydropic fetuses were available for analysis, 50 in the high-output
      group and 19 in the low-output group. The peak velocity index, preload index, and
      the pulsatility index of the DV were significantly low in the high-output group,
      whereas they were significantly high in the low-output group. The umbilical vein
      pulsations were found in 78.9% of the fetuses with low-output hydrops fetalis but
      only 28.0% of fetuses in the high output group (P < .001). CONCLUSION: New
      insights gained from this study are that hydrops caused by severe anemia because
      of hemoglobin Bart's is not associated with high central venous pressures as is
      seen in hydropic fetuses with coronary heart disease. This suggests that cardiac
      decompensation is not the primary mechanism of hydrops in these anemic fetuses.
      Additionally, umbilical vein pulsations are not a sign of cardiac failure in the
      anemic group.

PMID- 20684947
TI  - Heparanase, heparan sulfate and perlecan distribution along with the vascular
      penetration during stellate reticulum retraction in the mouse enamel organ.
AB  - OBJECTIVE: Immunohistochemical and gene expression profiles of heparanase were
      determined in murine molar tooth germs from their embryonic to postnatal stages,
      paying special attention to neovascularization within the enamel organ, which is
      poorly vascularized before birth. DESIGN: Protein and gene expression profiles of
      heparanase, heparan sulfate (HS), vascular endothelial growth factor (VEGF),
      transforming growth factor-beta1 (TGF-beta1), and perlecan were comparatively
      examined by immunohistochemistry and in-situ hybridization, respectively, in
      mouse mandibular molar tooth germs from embryonic day 11.5 to postnatal day 6. At
      the same time, their mRNA expression levels were also confirmed by reverse
      transcriptase-polymerase chain reaction using laser-captured microdissection of
      enamel organ tissues. RESULTS: Stellate reticulum cells highly expressed perlecan
      but only slightly expressed heparanase and HS in their embryonic days. On and
      after postnatal day 1, the expressions of heparanase became dramatically higher
      in the stellate reticulum, while HS disappeared leaving the immunopositivity for
      perlecan core protein. Immunohistochemically, HS was enhanced around blood
      vessels which were newly formed after birth within the enamel organs, whose
      volume was also regressive. Similar expression patterns were obtained for VEGF
      and TGF-beta1. CONCLUSIONS: Such synchronized expression modes among the HS
      metabolism-related molecules suggested that heparanase plays an important role in
      degradation of HS chains, which is closely related to vascular penetration into
      the stellate reticulum, which may be one of the driving forces for the postnatal
      regression of the enamel organ.

PMID- 20684949
TI  - The structure of the O-antigen of Cronobacter sakazakii HPB 2855 isolate involved
      in a neonatal infection.
AB  - Strains of Cronobactersakazakii (previously known as Enterobactersakazakii) are
      medically recognized important Gram-negative bacterial pathogens that cause
      enterocolitis, septicemia, and meningitis, with a high mortality rate in
      neonates. The structure of their O-antigens, that form part of their somatic
      lipopolysaccharide (LPS) components, is of interest for their chemical and
      serological identification and their relationship to virulence. The O
      polysaccharide (O-PS) of C.sakazakii HPB 2855 (SK 81), a strain isolated from an
      infant at the Hospital for Sick Children in Toronto in 1981, was shown to be a
      polymer of a partially O-acetylated-repeating hexasaccharide unit composed of d
      glucose, d-galacturonic acid, 2-acetamido-2-deoxy-d-galactose, and l-rhamnose
      (1:1:1:3). From composition and methylation analysis, and the application of 1D
      and 2D (1)H and (13)C NMR spectroscopy, the O-PS was determined to be a polymer
      of a repeating oligosaccharide unit having the structure:

PMID- 20684950
TI  - [Surgeon-oncology patient communication: an unresolved matter].

PMID- 20684951
TI  - Spiral wave breakup in excitable media with an inhomogeneity of conduction
      anisotropy.
AB  - Many conditions remodel the heart muscle such that it results in a perturbation
      of cells coupling. The effect of this perturbation on the stability of the spiral
      waves of electrochemical activity is not clear. We used the FitzHugh-Nagumo model
      of an excitable medium to model the conduction of the activation waves in a two
      dimensional system with inhomogeneous anisotropy level. Inhomogeneity of the
      anisotropy level was modeled by adding Gaussian noise to diffusion coefficients
      corresponding with lateral coupling of the cells. Low noise levels resulted in a
      stable propagation of the spiral wave. For large noise level conduction was not
      possible due to insufficient coupling in direction perpendicular to fibers. For
      intermediate noise intensities, the initial wave broke up into several
      independent spiral waves or waves circulating around conduction obstacles. At an
      optimal noise intensity, the number of wavelets was maximized-a form of anti
      coherent resonance was obtained. Our results suggest that the inhomogeneity of
      conduction anisotropy may promote wave breakup and hence play an important role
      in the initiation and perpetuation of the cardiac arrhythmias.

PMID- 20684952
TI  - Cross-linguistic neuroimaging and dyslexia: a critical view.
AB  - Recent neuro-cognitive theories of dyslexia presume that all dyslexics have the
      same type of brain abnormality irrespective of the particular writing system
      their language uses. In this article, we indicate how this presumption is
      inconsistent with cross-linguistic investigations of reading and dyslexia. There
      are two main issues. First, the information-processing requirements of reading
      vary greatly across different orthographies. Second, it is known that even within
      a single orthography there are different subtypes of dyslexia. Consequentially,
      it cannot be the case, not even within a single orthography let alone across
      orthographies, that all dyslexics have the same type of brain abnormality. Neuro
      cognitive theorizing about dyslexia cannot afford to ignore these issues.

PMID- 20684953
TI  - Androgen excess down-regulates connexin43 in a human granulosa cell line.
AB  - By use of a cell model, we found that high levels of androgen reduce connexin43
      expression and impair gap junction intercellular communication between human
      granulosa cells through the androgen receptors. High levels of androgen may
      impair folliculogenesis and in turn lead to ovulatory dysfunction in polycystic
      ovary syndrome patients.

PMID- 20684954
TI  - Gonadotropin-releasing hormone agonists versus antagonists for controlled ovarian
      hyperstimulation in oocyte donors: a systematic review and meta-analysis.
AB  - OBJECTIVE: To compare GnRH agonists and antagonists in oocyte-donation IVF
      treatment cycles by a systematic review and meta-analysis of trials. DESIGN:
      Systematic review and meta-analysis of randomized clinical trials (RCT).
      Systematic literature searches were conducted, and all randomized trials that
      compared GnRH agonists with antagonists in oocyte-donation IVF treatment cycles
      were included. Study selection, quality appraisal, and data extractions were
      performed independently and in duplicate. SETTING: Tertiary fertility center.
      PATIENT(S): A total of 1,024 oocyte donors treated in eight RCTs.
      INTERVENTION(S): Comparison of GnRH agonists versus antagonists in oocyte
      donation IVF treatment. MAIN OUTCOME MEASURE(S): Ongoing pregnancy, oocytes
      retrieved, duration of stimulation, gonadotropin consumption, and ovarian
      hyperstimulation syndrome incidence (OHSS) per randomized oocyte donor.
      RESULT(S): Meta-analysis of these studies showed no significant difference in
      ongoing pregnancy rate between the GnRH agonists and antagonists (risk ratio [RR]
      1.15, 95% confidence interval [CI] 0.97 to 1.36). The duration of stimulation was
      significantly lower with the GnRH antagonist protocol (weighed mean difference
      [WMD] -0.90 days, 95% CI -1.61 to -0.20). No significant differences were
      observed in the number of oocytes retrieved (WMD -0.60, 95% CI -2.26 to +1.07),
      gonadotropin consumption (WMD -264 IU, 95% CI -682 to +154), or OHSS incidence
      (RR 0.62, 95% CI 0.18 to 2.15). CONCLUSION(S): No significant differences were
      observed in ongoing pregnancy rate or the number of retrieved oocytes after donor
      stimulation with GnRH agonist or antagonist protocols.

PMID- 20684955
TI  - Effect of the insulin sensitizers metformin and pioglitazone on endothelial
      function in young women with polycystic ovary syndrome: a prospective randomized
      study.
AB  - OBJECTIVE: To compare the effect of two different insulin sensitizers, metformin
      and pioglitazone, on endothelial function in women with polycystic ovary syndrome
      (PCOS). DESIGN: Prospective randomized study. SETTING: University Hospital
      endocrinology outpatient clinic. PATIENT(S): Young women with PCOS (aged 23.3+/
      4.9 years). INTERVENTION(S): Patients were assigned randomly to no treatment
      (n=14), metformin 850 mg two times per day (n=15), and pioglitazone 30 mg daily
      (n=14) for 6 months. Healthy age- and body mass index-matched women served as
      controls (n=14). MAIN OUTCOME MEASURE(S): Brachial artery flow-mediated dilation
      was studied at baseline and 6 months. RESULT(S): Women with PCOS had higher
      insulin resistance and hyperandrogenism indices and lower flow-mediated dilation
      compared with controls. The three groups of women with PCOS did not differ at
      baseline. No differences were observed at follow-up in women who received no
      treatment. Metformin and pioglitazone improved flow-mediated dilation to a
      similar extent, restoring it to normal values at 6 months. Both insulin
      sensitizers induced favorable changes in insulin resistance and hyperandrogenism
      indices in women with PCOS. Independent predictors of flow-mediated dilation
      improvement at 6 months were treatment with insulin sensitizers and reduction in
      insulin resistance. CONCLUSION(S): In young women with PCOS, treatment with
      metformin or pioglitazone for 6 months induces a similar beneficial effect on
      endothelial function; this may be partially attributed to an improvement in
      insulin resistance. Further research is needed to investigate whether treatment
      with insulin sensitizers in women with PCOS also reduces cardiovascular risk.

PMID- 20684956
TI  - Altered levels of seminal nitric oxide, nitric oxide synthase, and enzymatic
      antioxidants and their association with sperm function in infertile subjects.
AB  - OBJECTIVE: To investigate the association between specific reactive nitrogen
      species and sperm function among infertile subjects. DESIGN: Controlled trial.
      SETTING: Fertility clinic at the National Institute of Health and Family Welfare,
      New Delhi, India. PATIENT(S): Proven fertile volunteers and subjects attending
      the above clinic. INTERVENTION(S): Tests for hypo-osmotic swelling (HOS), nuclear
      chromatin decondensation (NCD), acrosomal status (AS) were performed, and total
      nitric oxide (NO), nitric oxide synthase (NOS), superoxide dismutase (SOD), and
      catalase were assayed in infertile subjects subgrouped on the basis of routine
      sperm parameters. MAIN OUTCOME MEASURE(S): Correlation between sperm function and
      total NO, SOD, catalase, and NOS levels in semen. RESULT(S): Most of the
      infertile subjects were found to possess high NO and NOS activity in the semen.
      Leukocytospermic subjects, despite having normal sperm motility and viability,
      demonstrated subnormal sperm function scores. Nitric oxide in semen was inversely
      associated with sperm function in normospermia, asthenospermia, leukocytospermia,
      leukocytoasthenospermia, and teratospermia. In oligospermia with normal or
      subnormal motility, NO was positively associated with sperm function. Attenuated
      activities of either SOD or catalase or both were observed in all infertile
      subjects except those with normospermia. CONCLUSION(S): Subnormal sperm function
      in normospermia, asthenospermia, and leukocytospermia may be due to the cytotoxic
      effect of increased NO, whereas in oligospermia the same may be due to low or
      suboptimal levels.

PMID- 20684957
TI  - Patient specific quantitative analysis of fracture fixation in the proximal femur
      implementing principal strain ratios. Method and experimental validation.
AB  - Computational patient-specific modeling has the potential to yield powerful
      information for selection and planning of fracture treatments if it can be
      developed to yield results that are rapid, focused and coherent from a clinical
      perspective. In this study we introduce the utilization of a principal strain
      fixation ratio measure (SR) defined as the ratio of principal strains that
      develop in a fixated bone relative to the principal strains that develop in the
      same bone in an intact state. The SR field output variable is theoretically
      independent of load amplitude and also has a direct clinical interpretation with
      SR<1-a representing stress shielding and SR>1+b representing overstressed bone. A
      combined experimental and numerical study was performed with cadaveric proximal
      femora (n=6) intact and following fracture fixation to quantify the performance
      of the SR variable in terms of accuracy and sensitivity to uncertainties in
      density-elasticity relationships and load amplitude as model input variables. For
      a given axial compressive force the SR field output variable was found to be less
      sensitive to changes in density-elasticity relationships and the response
      function to be more accurate than strain values themselves; errors were reduced
      by 44% on comparing SR with strain in the fixated model. In addition, the
      experimental data confirmed the assumption that the SR values behave independent
      of load amplitude. The load independent behavior of SR and its direct clinical
      interpretation may ultimately provide an appropriate and easily understood
      comparative computational measure to choose between patient specific fracture
      fixation alternatives.

PMID- 20684958
TI  - Application of a quick, easy, cheap, effective, rugged and safe-based method for
      the simultaneous extraction of chlorophenols, alkylphenols, nitrophenols and
      cresols in agricultural soils, analyzed by using gas chromatography-triple
      quadrupole-mass spectrometry/mass spectrometry.
AB  - Due to the different physico-chemical properties of phenols, the development of a
      methodology for the simultaneous extraction and determination of phenolic
      compounds belonging to several families, such as chlorophenols (CPs),
      alkylphenols (APs), nitrophenols (NTPs) and cresols is difficult. This study
      shows the development and validation of a method for the analysis of 13 phenolic
      compounds (including CPs, APs, NTPs and cresols) in agricultural soils. For this
      purpose, a quick, easy, cheap, effective, rugged and safe (QuEChERS)-based
      procedure was developed, validated and applied to the analysis of real samples. A
      derivatization step prior to the final determination by gas chromatography (GC)
      coupled to a triple quadrupole analyzer operating in tandem mass spectrometry
      (QqQ-MS/MS) was performed by using acetic acid anhydride (AAA) and pyridine (Py).
      The optimized procedure was validated, obtaining average extraction recoveries in
      the range 69-103% (10microgkg(-1)), 65-98% (50microgkg(-1)), 76-112%
      (100microgkg(-1)) and 76-112% (300microgkg(-1)), with precision values (expressed
      as relative standard deviation, RSD)< or =22% (except for 4-chlorophenol)
      involving intra-day and inter-day studies. Furthermore, 15 real soil samples were
      analyzed by the proposed method in order to assess its applicability. Some
      phenolic compounds (e.g. 2,4,6-trichlorophenol or 4-tert-octylphenol) were found
      in the samples at trace levels (<10microgkg(-1)).

PMID- 20684959
TI  - Heterologous expression and N-terminal His-tagging processes affect the catalytic
      properties of staphylococcal lipases: a monolayer study.
AB  - The interfacial and kinetic properties of wild type, untagged recombinant and
      tagged recombinant forms of three staphylococcal lipases (SSL, SXL and SAL3) were
      compared using the monomolecular film technique. A kinetic study on the
      dependence of the stereoselectivity of these nine lipase forms on the surface
      pressure was performed using the three dicaprin isomers spread in the form of
      monomolecular films at the air-water interface. New parameters, termed
      Recombinant expression Effects on Catalysis (REC), N-Tag Effects on Catalysis
      (TEC), and N-Tag and Recombinant expression Effects on Catalysis (TREC), were
      introduced. The findings obtained showed that with all the lipases tested, the
      recombinant expression process and the N-terminal His-tag slightly affect the sn
      1 preference for dicaprin enantiomers as well as the penetration capacity into
      monomolecular films of phosphatidylcholine but significantly decrease the
      catalytic rate of hydrolysis of three dicaprin isomers. This rate reduction is
      more pronounced at high surface pressures, i.e. at low interfacial energies. In
      conclusion, the effects of the heterologous expression process on the catalytic
      properties of the staphylococcal lipases are three times more deleterious than
      the presence of an N-terminal tag extension. In the case of the situation most
      commonly encountered in the literature, i.e. the heterologous expression of a
      tagged lipase, the rate of catalysis can be decreased by these processes by 42
      83% on average in comparison with the values measured with the corresponding wild
      type form.

PMID- 20684960
TI  - A facile process for generating monolithic-structured nano-silica/polystyrene
      multi-core/shell microspheres by a seeded sol-gel process method.
AB  - Monodisperse "monolithic-structured" organic-inorganic composite microspheres
      were produced by a seeded sol-gel process method. A large number of nano-silica
      particles were generated and dispersed in the inner domains of the obtained
      microspheres. Seed particles were prepared by dispersion co-polymerization of
      styrene and (trimethoxysilyl)propyl 2-methylprop-2-enoate (TMSPM). The seed
      particles were swollen with an emulsified tetraethoxysilane (TEOS) in 0.25 wt.%
      sodium dodecylsulfate (SDS) aqueous solutions. Then the sol-gel reaction was
      conducted with ammonium hydroxide after completion of the swelling process. In
      contrast to conventional methods, the sol-gel reaction occurred in the inner
      space of the prepared template particles and monolithic-structured nano-silica
      and polystyrene organic-inorganic composite microspheres were obtained. The
      synthetic procedure for composite particles was studied by utilizing transmission
      electron microscopy (TEM), scanning electron microscopy (SEM), Fourier transform
      infrared spectroscopy (FT-IR), and thermo-gravimetric analysis (TGA).

PMID- 20684961
TI  - A low-voltage nano-porous electroosmotic pump.
AB  - A low-voltage electroosmotic (EO) micropump based on an anodic aluminum oxide
      (AAO) nano-porous membrane with platinum electrodes coated on both sides has been
      designed, fabricated, tested, and analyzed. The maximum flow rate of 0.074 ml
      min(-1) V(-1) cm(-2) for a membrane with porosity of 0.65 was obtained. A
      theoretical model, considering the head loss along the entire EO micropump system
      and the finite electrical double layer (EDL) effect on the flow rate, is
      developed for the first time to analyze the performance of the EO micropump. The
      theoretical and experimental results are in good agreement. It is revealed that
      the major head loss could remarkably decrease the flow rate, which thus should be
      taken into account for the applications of the EO micropump in various Lab-on-a
      chip (LOC) devices. However, the effect of the minor head loss on the flow rate
      is negligible. The resulting flow rate increases with increasing porosity of the
      porous membrane and kappaa, the ratio of the radius of the nanopore to the Debye
      length.

PMID- 20684962
TI  - Neuroradiology in Europe--past, present and future.

PMID- 20684963
TI  - Household-based prevalence of helminths and parasitic protozoa in rural KwaZulu
      Natal, South Africa, assessed from faecal vault sampling.
AB  - This study was undertaken to examine the family-based prevalence of
      environmentally persistent parasites in two rural communities of KwaZulu-Natal,
      South Africa. Samples were collected from 120 urine-diversion family toilets and
      screened for selected protozoa and helminths with immunomagnetic separation and
      the ammonium bicarbonate (AMBIC) protocol respectively. The parasites found were
      Ascaris lumbricoides (59%), Giardia intestinalis (54%), Trichuris trichiura
      (48%), Cryptosporidium spp. (21%) and Taenia spp. (18%). Only 14% of the
      household toilets were negative for these pathogens. The occurrence of A.
      lumbricoides and T. trichiura was lower (P<0.001) in the area with better hygiene
      behaviour, whereas G. intestinalis was more common (P<0.05) in families with at
      least one child aged five years or less and in families with more than four
      persons. Quantification of the parasites per gram was done for each sample and
      this provided realistic risk assessment data for the reuse of material from urine
      diversion toilets. The high occurrence of parasites found in the two communities,
      in spite of sanitation and hygiene interventions in the areas, suggests an
      endemicity that will not be reduced without de-worming campaigns. Finally, the
      study showed that sampling directly from the deposited faecal material may be
      useful for parasitic prevalence estimations.

PMID- 20684964
TI  - The association of acute aortic dissection with Helicobacter pylori virulence
      specific serotypes: Distinct diversity of systemic antibodies to CagA and VacA
      genotypes.
AB  - BACKGROUND: Previous studies reported an association between chronic Helicobacter
      pylori infection and cardiovascular disease; however, controversy still exists
      regarding the presence of bacterial genomic material in atherosclerotic plaques.
      Currently, the genetic polymorphisms of H. pylori have been investigated and many
      virulence factors have been identified. No one has tried to associate these
      polymorphisms with aortic dissections. This study evaluated whether more virulent
      strains of H. pylori represent a risk factor for acute ascending aorta
      dissections. METHODS: The serologic status for H. pylori and type I strains were
      determined in 100 patients who underwent operative repair of acute, ascending
      aorta dissection and in 100 population-based control subjects matched fully for
      clinical, demographic, and socioeconomic characteristics. The specimens from
      dissected aorta were evaluated to identify the presence of bacterial genomic
      material in surgical patients. RESULTS: No evidence of genomic material from H.
      pylori was found in the specimens. The prevalence of positive H. pylori serology
      was greater in patients than in controls (72 vs 50) with an adjusted odds ratio
      2.8 (95% confidence interval, 1.8-4.1; P = .006). Patients with aortic dissection
      also had a greater prevalence of vacuolating cytotoxin gene subtypes s1m1 (73% vs
      31%) with an odds ratio of 6.0 (95% confidence interval, 3.1-11; P < .001).
      Patients who were positive for vacuolating cytotoxin gene subtypes s1m1 were
      similar in demographic and clinical features compared with other patients.
      CONCLUSION: The findings provide support for the hypothesis that an association
      exists between the more virulent type I strains of H. pylori (vacuolating
      cytotoxin gene subtypes s1m1) infection and acute aortic dissection. The
      mechanism(s) underlying the association remain to be elucidated.

PMID- 20684965
TI  - Chronic pancreatitis complicated by cavernous transformation of the portal vein:
      contraindication to surgery?
AB  - BACKGROUND: A subgroup of patients with chronic pancreatitis and severe
      incapacitating pain develop mesentericoportal vascular complications with
      extrahepatic portal hypertension (EPH) and subsequent cavernous transformation.
      The purpose of this study was to address the question of whether a
      noninterventional approach regarding surgery is justified. METHODS: A total of
      702 patients with chronic pancreatitis underwent major pancreatic surgery. EPH
      with cavernous transformation was diagnosed in 21 (3%; group C) and EPH without
      cavernous transformation in 60 (9%; group B). The remaining 621 patients (88%;
      group A) showed no evidence for extrahepatic hypertension or cavernous
      transformation. Prospectively collected data were analyzed with respect to
      perioperative parameters, outcomes, quality of life, and our previously
      established pain score. RESULTS: Patients in groups C and B had longer history
      and greater severity of pain (P = .0001). Group C had the longest operative times
      (P > .05) and greatest requirements of intraoperatively transfused packed red
      blood cells (P < .05). Morbidity was greater in group C compared with groups B
      and A (88% vs 55% vs 35%; P < .001). Mortality was 10% (2/21) in group C,
      compared with 1.3% (8/621) in group A and 0% in group B (P = .008). Quality of
      life as well as pain scores significantly improved postoperatively in group C,
      and were comparable to those in groups A and B (P < .001). CONCLUSION:
      Concomitant cavernous transformation in patients with chronic pancreatitis
      increases the operative risk significantly. Alternative treatment modalities
      should be evaluated thoroughly in every individual patient to offer every patient
      the best available treatment. Nevertheless, operative intervention is often the
      only treatment possible and improvements in quality of life and pain alleviation
      justify operative interventions.

PMID- 20684966
TI  - Inhibition of nuclear entry of HPV16 pseudovirus-packaged DNA by an anti-HPV16 L2
      neutralizing antibody.
AB  - Rabbit anti-HPV16 L2 serum (anti-P56/75) neutralizes multiple oncogenic human
      papillomaviruses (HPVs). We inoculated HeLa cells with HPV16 pseudovirus (16PV)
      and with anti-P56/75-bound 16PV (16PV-Ab). Both 16PV and 16PV-Ab attached equally
      well to the cell surface. However, the cell-attached L1 protein of 16PV became
      trypsin-resistant after incubation at 37 degrees C, whereas approximately 20% of
      the cell-attached 16PV-Ab L1 remained trypsin-sensitive. Confocal microscopy of
      HeLa cells inoculated with 16PV revealed packaged DNA in the nucleus at 22h after
      inoculation; however, nuclear DNA was not detected in cells inoculated with 16PV
      Ab. Electron microscopy of HeLa cells inoculated with 16PV showed particles
      located in multivesicular bodies, lamellar bodies, and the cytosol after 4h; no
      cytosolic particles were detected after inoculation with 16PV-Ab. These data
      suggest that anti-P56/75 inhibits HPV infection partly by blocking viral entry
      and primarily by blocking the transport of the viral genome to the nucleus.

PMID- 20684967
TI  - Analysis of parainfluenza virus-5 hemagglutinin-neuraminidase protein mutants
      that are blocked in internalization and degradation.
AB  - The PIV-5 hemagglutinin-neuraminidase (HN) protein is a multifunctional protein
      with sialic acid binding, neuraminidase and fusion promotion activity. HN is
      internalized by clathrin-mediated endocytosis and degraded. HN lacks
      internalization signals in its cytoplasmic tail but a single glutamic acid
      present at residue 37 at the putative transmembrane/ectodomain boundary is
      critical. We rescued rPIV-5 with mutations E37D or E37K, which have been shown to
      impair or abolish HN internalization, respectively. These viruses exhibited
      growth properties similar to wild-type (wt) virus but are impaired for fitness in
      tissue culture. Biochemical analysis of HN activities showed differences between
      HN E37D and HN E37K in fusion promotion and incorporation of HN and F into
      virions. Furthermore, oligomeric analyses indicate that HN E37 mutants perturb
      the tetrameric organization of HN, probably by destabilizing the dimer-of-dimers
      interface.

PMID- 20684968
TI  - Shrimp NF-kappaB binds to the immediate-early gene ie1 promoter of white spot
      syndrome virus and upregulates its activity.
AB  - The immediate-early gene ie1 carried by white spot syndrome virus (WSSV) exhibits
      very strong promoter activity and expresses highly throughout the infection
      cycle. Here we identified a NF-kappaB binding motif in the ie1 promoter region.
      Electrophoretic mobility shift assays indicated that the recombinant Rel homology
      domain (RHD) of shrimp NF-kappaB homolog LvRelish bound to the putative NF-kappaB
      site in the ie1 promoter. A transactivity assay of the WSSV ie1 promoter in
      Drosophila Schneider 2 cells demonstrated that LvRelish could increase ie1
      promoter activity. These results show that shrimp NF-kappaB homolog LvRelish
      transactivates WSSV ie1 gene expression and contributes to its high promoter
      activity. Further transactivation assays showed that WSSV IE1 protein expression
      upregulated the promoter activities of WSSV ie1 gene and antimicrobial peptide
      genes regulated by the NF-kappaB system. We suggested that WSSV may annex the
      shrimp NF-kappaB system, which it uses to enhance the expression of viral
      immediate-early genes.

PMID- 20684969
TI  - Status of groundwater arsenic contamination in Bangladesh: a 14-year study
      report.
AB  - Since 1996, 52,202 water samples from hand tubewells were analyzed for arsenic
      (As) by flow injection hydride generation atomic absorption spectrometry (FI-HG
      AAS) from all 64 districts of Bangladesh; 27.2% and 42.1% of the tubewells had As
      above 50 and 10 MUg/l, respectively; 7.5% contained As above 300 MUg/l, the
      concentration predicting overt arsenical skin lesions. The groundwater of 50
      districts contained As above the Bangladesh standard for As in drinking water (50
      MUg/l), and 59 districts had As above the WHO guideline value (10 MUg/l). Water
      analyses from the four principal geomorphological regions of Bangladesh showed
      that hand tubewells of the Tableland and Hill tract regions are primarily free
      from As contamination, while the Flood plain and Deltaic region, including the
      Coastal region, are highly As-contaminated. Arsenic concentration was usually
      observed to decrease with increasing tubewell depth; however, 16% of tubewells
      deeper than 100 m, which is often considered to be a safe depth, contained As
      above 50 MUg/l. In tubewells deeper than 350 m, As >50 MUg/l has not been found.
      The estimated number of tubewells in 50 As-affected districts was 4.3 million.
      Based on the analysis of 52,202 hand tubewell water samples during the last 14
      years, we estimate that around 36 million and 22 million people could be drinking
      As-contaminated water above 10 and 50 MUg/l, respectively. However for roughly
      the last 5 years due to mitigation efforts by the government, non-governmental
      organizations and international aid agencies, many individuals living in these
      contaminated areas have been drinking As-safe water. From 50 contaminated
      districts with tubewell As concentrations >50 MUg/l, 52% of sampled hand
      tubewells contained As <10 MUg/l, and these tubewells could be utilized
      immediately as a source of safe water in these affected regions provided regular
      monitoring for temporal variation in As concentration. Even in the As-affected
      Flood plain, sampled tubewells from 22 thanas in 4 districts were almost entirely
      As-safe. In Bangladesh and West Bengal, India the crisis is not having too little
      water to satisfy our needs, it is the challenge of managing available water
      resources. The development of community-specific safe water sources coupled with
      local participation and education are required to slow the current effects of
      widespread As poisoning and to prevent this disaster from continuing to plague
      individuals in the future.

PMID- 20684970
TI  - Impact of inocula and growth mode on the molecular microbial ecology of anaerobic
      ammonia oxidation (anammox) bioreactor communities.
AB  - The composition of distinctly inoculated granular anammox and biofilm-based
      completely autotrophic nitrogen removal over nitrite (CANON) bioreactors was
      investigated from start-up through continuous long-term operation via denaturing
      gradient gel electrophoresis (DGGE) and sequencing. The granular anammox reactor
      was seeded with sludge from an operational anammox reactor in Strass, Austria.
      The CANON reactor was seeded with activated sludge from a local wastewater
      treatment plant in New York City. The principal anammox bacteria (AMX) shifted
      from members related to Kuenenia stuttgartiensis present in the initial inoculum
      to members related to Candidatus Brocadia fulgida during pre-enrichment (before
      this study) and to members related to Candidatus Brocadia sp. 40 (during this
      study) in the granular reactor. AMX related to C. Brocadia sp. 40 were also
      enriched from activated sludge in the CANON reactor. The estimated doubling times
      of AMX in the granular and CANON reactors were 5.3 and 8.9 days, respectively,
      which are lower than the value of 11 days, reported previously. Both the granular
      anammox and CANON reactors also fostered significant amounts of ammonia-oxidizing
      bacteria (AOB) and nitrite-oxidizing bacteria (NOB). The fractions of AMX and two
      groups of NOB were generally similar in the granular anammox and CANON reactors.
      However, the diversity and fractions of AOB in the two reactors was markedly
      different. Therefore, it is suggested that the composition of the feed and extant
      substrate concentrations in the reactor likely select for the microbial community
      composition more than the inocula and reactor configuration. Further, such
      selection is not equivalent for all resident communities.

PMID- 20684971
TI  - A comparison of membrane fouling under constant and variable organic loadings in
      submerge membrane bioreactors.
AB  - The aim of this study is to compare the effect of constant and variable influent
      organic loadings on membrane fouling in submerged membrane bioreactors (sMBRs).
      Two identical lab-scale sMBRs were operated for 162 days at an SRT of 30 days,
      whereas the influent organic loading was kept constant in one MBR, and varied in
      another. The microbial characteristics of sludge in terms of MLSS, bound EPS, EPS
      in the supernatant and particle size distribution were investigated in order to
      evaluate their respective effect on membrane fouling. During the start-up period,
      membrane fouling in the MBR fed with variable loadings was more serious than that
      in the MBR with the constant loading. However, at the stable state, the fouling
      tendency was clearly reversed with less membrane fouling for variable feed
      strength. It was shown that the contents of polysaccharides in the supernatant
      and particle size of the bioflocs were responsible for the observed differences
      in the fouling tendencies of the two MBRs.

PMID- 20684972
TI  - Processes releasing arsenic to groundwater in the Caldes de Malavella geothermal
      area, NE Spain.
AB  - Arsenic concentrations exceeding the World Health Organization drinking water
      guideline (10 MUg/L) have been measured in thermal and non-thermal groundwaters
      from the Caldes de Malavella geothermal area (La Selva graben, NE Spain). The
      CO(2)-rich Na-HCO(3) thermal waters (up to 60  degrees C at the spring) have
      elevated arsenic concentrations ([As(T)] from 50 to 80 MUg/L). The non-thermal
      waters are of Ca-Na-HCO(3)-Cl type and have [As(T)] between <1 and 200 MUg/L,
      defining a hot-spot distribution. The present-day contribution of As from CO(2)
      rich thermal waters to non-thermal aquifers is very limited, as shown by the
      concentration of geothermal tracers such as Li and B. Redox-controlling processes
      appear to govern the mobility of As in the non-thermal waters. Arsenate is
      clearly predominant in most oxidizing groundwaters (>85% of As(V) over total As),
      whereas reducing, high-As groundwater reaches up to 100% in arsenite. The
      reductive dissolution of Fe(III) oxyhydroxides and the coupled release and
      reduction of adsorbed As explain the elevated dissolved arsenite (up to 190
      MUg/L) and Fe (up to 14 mg/L) content in the more reducing non-thermal
      groundwater. Conversely, the high levels of nitrate (up to 136 mg/L) ensure an
      oxidizing environment in most non-thermal groundwaters ([As(T)] between <1 and 60
      MUg/L). Under these conditions, Fe(III) oxyhydroxides are stable and As release
      to groundwater is not related to their dissolution. Instead, dissolved arsenate
      concentrations up to 60 MUg/L are explained by a competition for sorption sites
      with other species, mainly bicarbonate and silicic acid, while arsenate
      desorption due to pH increase is not considered a major process.

PMID- 20684973
TI  - Absorption and translocation of polybrominated diphenyl ethers (PBDEs) by plants
      from contaminated sewage sludge.
AB  - Polybrominated diphenyl ethers (PBDEs) are used as additive flame retardants.
      PBDEs are persistent, bioaccumulative and toxic compounds. They are often
      detected in sewage sludge which is applied on agricultural soils as fertilizer.
      The objective of this study was to find out whether plants are able to accumulate
      and translocate PBDEs. Tobacco (Nicotiana tabacum) and nightshade (Solanum
      nigrum) were planted in pots containing contaminated sewage sludge and
      uncontaminated substrate. After 6 months of plant cultivation in sewage sludge up
      to 15.4 ng g(-1) dw and 76.6 ng g(-1) dw of PBDE congeners--BDE 47, BDE 99 and
      BDE 100---were accumulated in the nightshade and tobacco tissue, respectively.
      Corresponding values in plants vegetated in the control garden substrate were 10
      times lower. The bioconcentration factors (BCFs) of accumulated congeners were
      calculated. Tobacco exhibited higher BCFs values and for both plants BCFs values
      of BDE 47, BDE 99, BDE 100 and BDE 209 negatively correlated with their octanol
      water partition coefficients (logK(ow)). The exception was decaBDE (BDE 209)
      which was accumulated only in tobacco tissue in the concentration of 116.8 ng g(
      1) dw. The majority of PBDEs was detected in above-ground plant biomass
      indicating that both plants have the ability to translocate PBDEs. To our
      knowledge this is one of the first studies reporting the accumulation of both
      lower PBDEs and BDE 209 in plants. Our results suggest that absorption,
      accumulation and translocation of PBDEs by plants and their transfer to the food
      chain could represent another possible risk for human exposure.

PMID- 20684974
TI  - Quantification of herbicide removal in a constructed wetland using passive
      samplers and composite water quality monitoring.
AB  - Constructed wetlands used as treatment for urban stormwater have the potential to
      improve water quality. This study aimed to estimate the removal of selected
      herbicides in stormwater by a constructed wetland using composite water quality
      monitoring and passive samplers. For the four week duration of the study the
      wetland was effective in reducing the concentrations of diuron, simazine and
      atrazine. Mean estimated concentrations over a 28 d period were 192, 70 and 5 ng
      L(-1) at the inlet and 94, 30 and 2 ng L(-1) at the outlet for diuron, simazine
      and atrazine, respectively. Concentrations of these herbicides generally halved
      as a result of passage through the constructed wetland with a design hydraulic
      retention time of 7d. Simple ratios of the inlet and outlet herbicide
      concentrations as well as hydraulic load-based methods of measuring the wetland's
      removal efficiency resulted in a range of estimations 33-51% for diuron and 20
      60% for simazine. Due to their lower detection limits, the use of passive
      samplers provides a more efficient technique than conventional sampling for
      assessment of stormwater wetland treatment.

PMID- 20684975
TI  - Effects of Roundup Transorb on fish: hematology, antioxidant defenses and
      acetylcholinesterase activity.
AB  - Roundup Transorb(RDT) is a glyphosate-based herbicide containing a mixture of
      surfactants. The objective of this work was to evaluate the effects of this
      herbicide on the Neotropical fish Prochilodus lineatus. Juvenile fish were
      acutely exposed (6, 24 and 96 h) to 1 mg L(-1) of RDT (RDT 1), 5 mg L(-1) of RDT
      (RDT 5) or only water (control) and blood samples for hematological analysis,
      liver for antioxidants analysis, and brain and muscle for acetylcholinesterase
      (AChE) determination, were collected. RDT effects were more evident in fish
      exposed to the higher concentration of the herbicide. Hematologic alterations
      appeared only after 96 h exposure, when fish showed an increase in the hematocrit
      and in the number of both red and white blood cells. After 6h exposure fish
      showed a transient reduction in superoxide dismutase and catalase activity. RDT
      also inhibited glutathione-S-transferase, after 6 and 24h of exposure. The
      reduction in these enzymes is probably related to the occurrence of lipid
      peroxidation (LPO) in fish exposed to the herbicide for 6h. LPO returned to
      control levels after 24 and 96 h exposure to RDT, when fish showed an increased
      activity of glutathione peroxidase. The content of reduced glutathione also
      increased after 96 h exposure. Thus, after 24 and 96 h the antioxidant defenses
      were apparently enough to combat ROS, preventing the occurrence of oxidative
      damage. The exposure to RDT for 96 h led to an inhibition of AChE in brain and
      muscle at rates which may not be considered a life-threatening situation.

PMID- 20684976
TI  - Casting light on 25-hydroxyvitamin D deficiency in ovarian cancer: a study from
      the NHANES.
AB  - OBJECTIVES: Ecological studies have long described a higher incidence of ovarian
      cancer in more extreme latitudes, where sun exposure, and presumably vitamin D
      exposure, is lower. Basic science studies have also noted polymorphisms of the
      vitamin D receptor in ovarian cancers. The aim of this study is to examine the
      relationship of serum vitamin D to ovarian cancer. METHODS: A case-control study
      of 7273 subjects from the National Health and Nutrition Examination Surveys
      (NHANES) was performed. Serum 25-hydroxyvitamin D (25[OH]D) levels were examined
      in both ovarian cancer patients and a control population. Logistic regression
      examined the odds of ovarian cancer for those with vitamin D levels below the
      median of the U.S. population. RESULTS: Ovarian cancer cases were more than three
      times more likely to have low 25[OH]D levels (OR 3.68, 95% CI 1.03-13.21,
      p=0.04). In the weighted multivariate model, the relationship persisted after
      adjusting for potential confounders, including age, body mass index, and diet.
      Adjusting for significant covariates, which included age and dietary calcium
      intake, ovarian cancer cases were nearly four times more likely to have low
      25[OH]D levels (OR 3.92, 95% CI 1.11-13.85, p=0.03). CONCLUSIONS: Prevalent
      ovarian cancer cases have lower serum 25-hydroxyvitamin D (25[OH]D) than the
      general population. Deficiency in vitamin D may provide an etiologic link between
      the long-known ecologic findings regarding latitude and the basic science noting
      polymorphisms in the vitamin D receptor.

PMID- 20684977
TI  - Effect of shrinkage strain, modulus, and instrument compliance on polymerization
      shrinkage stress of light-cured composites during the initial curing stage.
AB  - OBJECTIVES: The aim of this study was to investigate the influence of shrinkage
      strain, modulus, and instrument compliance on the polymerization shrinkage stress
      measurement of light-cured composites, and to determine whether the silorane
      based low-shrinkage composite shows a low-polymerization shrinkage stress.
      METHODS: A universal hybrid; Z250 (Z2), a flowable; Z350 (Z3), and a silorane
      based; P90 (P9) composite was examined. A modified "bonded disc method" was used
      to measure the axial shrinkage strain of the composite. For the measurement of
      the initial modulus development of composites during light curing, a dynamic
      oscillatory shear test was undertaken using a custom-made oscillation rheometer.
      A frequency of 6 Hz and strain amplitude of 0.0091 rad for 20 s was employed and
      the complex shear modulus (G(*)) was determined. A newly designed stress-strain
      analyzer was made to measure the shrinkage stress of the composites with two
      modes: (1) high compliance, or (2) low compliance. The shift between the two
      modes was controlled by an On-Off switch of a negative feedback circuit.
      Theoretical shrinkage stress was calculated from the shrinkage strain and modulus
      measured above, and compared with experimentally measured stress. Data were
      analyzed with one-way ANOVA and Tukey's post hoc test (alpha=0.05), and
      correlation analysis was done to investigate the relationship between measured
      stress and shrinkage strain, modulus, and theoretical stress. RESULTS: The
      shrinkage strain of Z3 (4.12%) at 10 min was the highest, followed by Z2 (2.31%)
      and P9 (0.77%). At 10 s after light curing, Z2 showed the highest modulus (466.2
      MPa), Z3 (154.1 MPa), and P9 the lowest (130.7 MPa). The measured stresses with
      low compliance were much higher than those with high compliance. With high
      compliance, the contraction stress of Z3 was the highest (2.75 MPa), followed by
      Z2 (1.54 MPa) and P9 (0.48 MPa). In low-compliance mode, the stresses of Z3 (7.93
      MPa) and Z2 (7.48 MPa) were similar (p=0.323) while the stress of P9 (3.23 MPa)
      was much lower. A strong correlation was observed between the theoretical stress
      and the measured stress with low compliance (R=0.996). In high-compliance mode,
      the shrinkage strain also showed a near-linear relationship with the stress
      measured (R=0.937), but the modulus showed a low correlation with the measured
      stress (R=0.398). SIGNIFICANCE: Depending on the instrument compliance,
      polymerization shrinkage stress showed significant differences for each material.
      In high-compliance shrinkage strain played a greater role, while in low
      compliance shrinkage strain and elastic modulus contributed comparably in
      determining the shrinkage stress. The low-shrinkage silorane-based composite
      demonstrated considerable reduction in shrinkage strain and stress.

PMID- 20684978
TI  - Correlations between spectroradiometric and spectrophotometric colors of all
      ceramic materials.
AB  - OBJECTIVES: Color coordinates of translucent esthetic materials measured by
      traditional spectrophotometers (SP) would deviate from those measured by newly
      introduced spectroradiometers (SR), which might simulate the clinical viewing
      condition better. This study aimed to determine the correlations in the SP- and
      SR-based color coordinates and color differences of all-ceramic materials.
      METHODS: Specimens for seven A2 shade core ceramics (n=7) and corresponding A2
      and A3 shades veneer ceramics (n=7) were fabricated in clinically relevant
      thicknesses (1.5mm after layering). Color of layered specimens was measured
      according to the CIELAB color scale by a SP and a SR. Color differences
      (DeltaE(ab)(*)) between the reference ceramics and the corresponding layered
      ceramics were calculated. Correlations between SP- and SR-based color coordinates
      and color difference values were determined (alpha=0.05). RESULTS: SR-based color
      coordinates were significantly different from the SP-based values; however,
      general shifting trends by the instrument were observed. SP- and SR-based CIE a*,
      b* and chroma values showed significant correlations (p<0.05); however, the CIE
      L* values and the color differences with the reference showed no significant
      correlations (p>0.05). SIGNIFICANCE: The color coordinates representing the hue
      attribute (CIE a*, b* and chroma) measured by a spectrophotometer and a
      spectroradiometer showed significant correlations; however, the color coordinates
      and the color difference values were significantly different by the instrument.
      Therefore, color coordinates and the color difference values based on different
      instruments should not be compared directly.

PMID- 20684979
TI  - Are youths' feelings of entitlement always "bad"?: Evidence for a distinction
      between exploitive and non-exploitive dimensions of entitlement.
AB  - Previous personality research (e.g., Campbell et al., 2004) has described the
      sense of entitlement as an unifactorial construct. In this study, we examined
      characteristics of two potential facets of entitlement: exploitive entitlement,
      characterized by exploitive interactions and expectations of special treatment,
      and non-exploitive entitlement, or entitled beliefs that rest on notions of self
      worth and fairness. 466 college students (mean age = 20.5) completed a
      questionnaire consisting of unifactorial and two-factor measures of entitlement
      and other personality dispositions and attitudes. As expected, both exploitive
      and non-exploitive entitlement were positively related to the Psychological
      Entitlement Scale (PES; r = .51 and r = .43, respectively), an unifactorial
      measure of entitlement. In other respects, exploitive and non-exploitive
      entitlement had quite distinct correlates. Exploitive entitlement was uniquely
      related to higher levels of psychopathy and neuroticism, and lower levels of work
      orientation, social commitment, and self-esteem; whereas non-exploitive
      entitlement was uniquely associated with higher self-esteem.

PMID- 20684980
TI  - Ross principle and concept of a living valve.

PMID- 20684981
TI  - Long-term outcomes after autograft versus homograft aortic root replacement in
      adults with aortic valve disease: a randomised controlled trial.
AB  - BACKGROUND: The ideal substitute for aortic valve replacement in patients with
      aortic valve disease is not known. Our hypothesis was that the regulatory and
      adaptive properties of a living valve substitute could improve the long-term
      outcomes in patients. We therefore compared these outcomes after autograft aortic
      root replacement (Ross procedure) versus homograft aortic root replacement in
      adults. METHODS: Male and female patients (<69 years) requiring aortic valve
      surgery were randomly assigned in a one-to-one ratio to receive an autograft or a
      homograft aortic root replacement in one centre in the UK. The random allocation
      sequence was computer generated. Treatment was not masked. The primary endpoint
      was survival of patients at 10 years after surgery. This study is registered as
      an International Standard Randomised Controlled Trial, number ISRCTN03530985.
      FINDINGS: 228 patients were randomly assigned to receive an autograft or a
      homograft aortic root replacement. 12 patients were excluded because they were
      younger than 18 years; 108 in each group received the surgery they were assigned
      to and were analysed. There was one (<1%) perioperative death in the autograft
      group versus three (3%) in the homograft group (p=0.621). At 10 years, four
      patients died in the autograft group versus 15 in the homograft group. Actuarial
      survival at 10 years was 97% (SD 2) in the autograft group versus 83% (4) in the
      homograft group. Hazard ratio for death in the homograft group was 4.61 (95% CI
      1.71-16.03; p=0.0060). Survival of patients in the autograft group was similar to
      that in an age-matched and sex-matched British population (96%). INTERPRETATION:
      Our findings support the hypothesis that a living valve implanted in the aortic
      position can significantly improve the long-term outcomes in patients. FUNDING:
      Funding Magdi Yacoub Institute.

PMID- 20684982
TI  - Pericyte-based human tissue engineered vascular grafts.
AB  - The success of small-diameter tissue engineered vascular grafts (TEVGs) greatly
      relies on an appropriate cell source and an efficient cellular delivery and
      carrier system. Pericytes have recently been shown to express mesenchymal stem
      cell features. Their relative availability and multipotentiality make them a
      promising candidate for TEVG applications. The objective of this study was to
      incorporate pericytes into a biodegradable scaffold rapidly, densely and
      efficiently, and to assess the efficacy of the pericyte-seeded scaffold in vivo.
      Bi-layered elastomeric poly(ester-urethane)urea scaffolds (length = 10 mm; inner
      diameter = 1.3 mm) were bulk seeded with 3 x 10(6) pericytes using a customized
      rotational vacuum seeding device in less than 2 min (seeding efficiency > 90%).
      The seeded scaffolds were cultured in spinner flasks for 2 days and then
      implanted into Lewis rats as aortic interposition grafts for 8 weeks. Results
      showed pericytes populated the porous layer of the scaffolds evenly and
      maintained their original phenotype after the dynamic culture. After
      implantation, pericyte-seeded TEVGs showed a significant higher patency rate than
      the unseeded control: 100% versus 38% (p < 0.05). Patent pericyte-seeded TEVGs
      revealed extensive tissue remodeling with collagen and elastin present. The
      remodeled tissue consisted of multiple layers of alpha-smooth muscle actin- and
      calponin-positive cells, and a von Willebrand factor-positive monolayer in the
      lumen. These results demonstrate the feasibility of a pericyte-based TEVG and
      suggest that the pericytes play a role in maintaining patency of the TEVG as an
      arterial conduit.

PMID- 20684983
TI  - The effect of matrix characteristics on fibroblast proliferation in 3D gels.
AB  - Engineering synthetic hydrogels on a molecular basis to introduce natural
      features that are important in instructing cell behavior is becoming increasingly
      crucial in biomaterial-based approaches for regenerative medicine and in cell
      biology to study cell-matrix interactions in three-dimensions (3D). Here, we used
      collagen gels and exploited the design flexibility of the biological, biochemical
      and physical characteristics offered by a PEG-based hydrogel system to
      systematically study the effect of specific extracellular microenvironments on
      the behavior of primary human fibroblasts in 3D. We firstly found that the
      proliferation profiles of fibroblasts from different patients cultured within
      collagen gels (3D) differed significantly from their behavior observed on tissue
      culture plastic (2D). Furthermore, using the biomimetic PEG-based matrix we
      showed that cell proliferation in 3D could be selectively manipulated via
      alteration of the gel characteristics. In particular, this study revealed that,
      in spite of matrix sensitivity to proteases (e.g. MMP) and the presence of cell
      integrin binding sites, at high stiffness (elastic modulus, G' >1200 Pa) the
      matrix acts as a barrier for cells cultured in 3D. Finally, a comparison between
      the biomimetic PEG-based and collagen gels indicated that differences in their
      viscoelastic behaviours, determined by the nature of network structures and cross
      links, may influence the mechanism(s) cells employ to remodel their 3D
      extracellular microenvironment. In conclusion, these studies highlight that for
      proliferation in 3D, compared to 2D, cells require strategies to overcome the
      physical impediment posed by the matrix. We also demonstrate that by exploiting
      the design flexibility of the characteristics offered by these biomimetic
      hydrogels, it is possible to separately investigate complex aspects
      characterizing the cell-matrix interactions in 3D; this has the potential to have
      great impact in regenerative medicine, as well as in cell biology and cancer
      research.

PMID- 20684984
TI  - The use of vascular endothelial growth factor functionalized agarose to guide
      pluripotent stem cell aggregates toward blood progenitor cells.
AB  - The developmental potential of pluripotent stem cells is influenced by their
      local cellular microenvironment. To better understand the role of vascular
      endothelial growth factor (VEGFA) in the embryonic cellular microenvironment, we
      synthesized an artificial stem cell niche wherein VEGFA was immobilized in an
      agarose hydrogel. Agarose was first modified with coumarin-protected thiols. Upon
      exposure to ultra-violet excitation, the coumarin groups were cleaved leaving
      reactive thiols to couple with maleimide-activated VEGFA. Mouse embryonic stem
      cells (ESC) aggregates were encapsulated in VEGFA immobilized agarose and
      cultured for 7 days as free-floating aggregates under serum-free conditions.
      Encapsulated aggregates were assessed for their capacity to give rise to blood
      progenitor cells. In the presence of bone morphogenetic protein-4 (BMP-4), cells
      exposed to immobilized VEGFA upregulated mesodermal markers, brachyury and VEGF
      receptor 2 (T+VEGFR2+) by day 4, and expressed CD34 and CD41 (CD34+CD41+) on day
      7. It was found that immobilized VEGFA treatment was more efficient at inducing
      blood progenitors (including colony forming cells) on a per molecule basis than
      soluble VEGFA. This work demonstrates the use of functionalized hydrogels to
      guide encapsulated ESCs toward blood progenitor cells and introduces a tool
      capable of recapitulating aspects of the embryonic microenvironment.

PMID- 20684985
TI  - The kinetics of the tissue distribution of silver nanoparticles of different
      sizes.
AB  - Blood kinetics and tissue distribution of 20, 80 and 110 nm silver nanoparticles
      were investigated in rats up to 16 days after intravenous administration once
      daily for 5 consecutive days. Following both single and repeated injection,
      silver nanoparticles disappeared rapidly from the blood and distributed to all
      organs evaluated (liver, lungs, spleen, brain, heart, kidneys and testes)
      regardless of size. The 20 nm particles distributed mainly to liver, followed by
      kidneys and spleen, whereas the larger particles distributed mainly to spleen
      followed by liver and lung. In the other organs evaluated, no major differences
      between the sizes were observed. Size-dependent tissue distribution suggests size
      dependent toxicity and health risks. Repeated administration resulted in
      accumulation in liver, lung and spleen, indicating that these organs may be
      potential target organs for toxicity after repeated exposure. A physiologically
      based pharmacokinetic (PBPK) model for nanoparticles which describes the kinetics
      of silver nanoparticles was developed. Model parameter values were estimated by
      fitting to data. No clear relation between parameter values and corresponding
      particle diameters became apparent.

PMID- 20684986
TI  - A review on endogenous regenerative technology in periodontal regenerative
      medicine.
AB  - Periodontitis is a globally prevalent inflammatory disease that causes the
      destruction of the tooth-supporting apparatus and potentially leads to tooth
      loss. Currently, the methods to reconstitute lost periodontal structures (i.e.
      alveolar bone, periodontal ligament, and root cementum) have relied on
      conventional mechanical, anti-infective modalities followed by a range of
      regenerative procedures such as guided tissue regeneration, the use of bone
      replacement grafts and exogenous growth factors (GFs), and recently developed
      tissue engineering technologies. However, all current or emerging paradigms have
      either been shown to have limited and variable outcomes or have yet to be
      developed for clinical use. To accelerate clinical translation, there is an
      ongoing need to develop therapeutics based on endogenous regenerative technology
      (ERT), which can stimulate latent self-repair mechanisms in patients and harness
      the host's innate capacity for regeneration. ERT in periodontics applies the
      patient's own regenerative 'tools', i.e. patient-derived GFs and fibrin
      scaffolds, sometimes in association with commercialized products (e.g. Emdogain
      and Bio-Oss), to create a material niche in an injured site where the
      progenitor/stem cells from neighboring tissues can be recruited for in situ
      periodontal regeneration. The choice of materials and the design of implantable
      devices influence therapeutic potential and the number and invasiveness of the
      associated clinical procedures. The interplay and optimization of each niche
      component involved in ERT are particularly important to comprehend how to make
      the desired cell response safe and effective for therapeutics. In this review,
      the emerging opportunities and challenges of ERT that avoid the ex vivo culture
      of autologous cells are addressed in the context of new approaches for
      engineering or regeneration of functional periodontal tissues by exploiting the
      use of platelet-rich products and its associated formulations as key endogenous
      resources for future clinical management of periodontal tissue defects.

PMID- 20684987
TI  - Aberrant protein expression in the placenta of cloned mouse derived from
      embryonic stem cell.
AB  - Placentomegaly is a common phenotype in cloned mice. To assess differences in
      protein expression between placentae of cloned and uncloned mice, we used a
      proteomic approach involving 2-dimensional electrophoresis (DE) and MALDI-TOF MS.
      Proteins within isoelectric point range of 4-11 separately were analyzed in 2-DE
      with 3 replications of each sample. A total of approximately 3500 spots were
      detected in placental 2-DE stained with Coomassie blue. In the comparison of
      normal and cloned samples, a total of 41 spots were identified as differentially
      expressed proteins, of which 25 spots were up-regulated proteins such as TIMP-2,
      glutamate-ammonia, and esterase 10, while 16 spots were down-regulated proteins
      such as PBEF and annexin A1. The TIMP-2, which is related to extracellular matrix
      degradation and tissue remodeling processes, is an inhibitor of MMP-2. The PBEF
      is related to inhibition of apoptosis and induction of spontaneous labor. Western
      blot analysis confirmed increased TIMP-2 expression and decreased PBEF expression
      in cloned placentae compared with normal controls. Our results demonstrated
      composite profiles of key proteins involved in abnormal hypertrophic placenta
      derived from cloned mice and suggested that the reason for the placentomegaly may
      be due to abnormal gene expression in cloned mice.

PMID- 20684988
TI  - MPN-associated myelofibrosis (MPN-MF).

PMID- 20684989
TI  - Prognostic factors in normal karyotype acute myeloid leukemia in the absence of
      the FLT3-ITD mutation.
AB  - Patients with normal karyotype acute myeloid leukemia (NK-AML) without the FLT3
      internal tandem duplication (FLT3-ITD) mutation account for approximately 30% of
      all AML cases, and exhibit a heterogeneous clinical outcome. Except for NPM1
      mutations, prognostic factors in this subgroup of AML are still unclear. Here we
      explored the impact of immunophenotypic markers along with NPM1 mutations and
      clinical features on the outcome of 133 FLT3-ITD negative NK-AML patients. CD34
      expression was associated with poorer complete remission (CR) rate, disease-free
      survival (DFS), event-free survival (EFS), and overall survival (OS), whereas
      CD56 expression adversely affected EFS and OS. In contrast, NPM1 mutations
      correlated with an improved CR rate, DFS, and EFS. Moreover, males experienced
      shorter DFS and EFS, while older patients (>=60 years) had shorter EFS.
      Multivariate analysis of age, gender, NPM1, CD34, and CD56 showed NPM1 mutation
      was an independent predictor of better CR rate, DFS, and EFS (P<0.001, P=0.003,
      and P=0.006, respectively). In addition, older age was associated with shorter
      DFS and EFS (P=0.045 and P=0.028, respectively), and CD56 positivity predicted
      shorter EFS (P=0.012). Our results confirm the favorable impact of NPM1 mutations
      and identify the adverse prognostic relevance of CD56 expression in this subgroup
      of AML.

PMID- 20684990
TI  - BEAM or BuCyE high-dose chemotherapy followed by autologous stem cell
      transplantation in non-Hodgkin's lymphoma patients: a single center comparative
      analysis of efficacy and toxicity.
AB  - We compared the efficacy and toxicity of BEAM (BCNU, etoposide, cytarabine and
      melphalan) and BuCyE (busulfan, cyclophosphamide and etoposide), given prior to
      autologous stem cell transplantation (ASCT), in 65 patients with non-Hodgkin's
      lymphoma. Of these 65 patients, 43 received BEAM and 22 received BuCyE. Their
      age, gender distribution, International Prognostic Index, status of disease at
      ASCT and median number of infused CD34(+) cells/kg were similar. Neutrophil and
      platelet engraftment were significantly faster in the BuCyE group. Rates of
      mucositis, nausea/vomiting, diarrhea, bleeding and infections were similar in the
      two groups. Median overall survival and event-free survival did not differ
      significantly between the two groups. These findings indicate that BuCyE is an
      effective conditioning regimen, showing similar survival outcomes and toxicity
      profiles as BEAM. Furthermore, hematologic recovery is significantly faster in
      patients given the BuCyE conditioning regimen.

PMID- 20684991
TI  - Genomic characterization of Imatinib resistance in CD34+ cell populations from
      chronic myeloid leukaemia patients.
AB  - To ascertain genomic alterations associated with Imatinib resistance in chronic
      myeloid leukaemia, we performed high resolution genomic analysis of CD34(+) cells
      from 25 Imatinib (IM) resistant and 11 responders CML patients. Using patients' T
      cells as reference, we found significant association between number of acquired
      cryptic copy number alterations (CNA) and disease phase (p=0.036) or loss of IM
      response for patients diagnosed in chronic phase (CP) (p=0.04). Recurrent cryptic
      losses were identified on chromosomes 7, 12 and 13. On chromosome 7, recurrent
      deletions of the IKZF1 locus were detected, for the first time, in 4 patients in
      CP.

PMID- 20684992
TI  - Mutagenicity and genotoxicity of tannery effluents used for irrigation at Kanpur,
      India.
AB  - The tannery effluents at Kanpur (India) have been in use for irrigation since
      last many years, polluting soil directly while ground water and food crops
      indirectly. Gas chromatography-mass spectrometric analysis of the test samples
      revealed the presence of organic compounds including diisooctyl phthalate, phenyl
      N-methylcarbamate, dibutyl phthalate, bis 2-methoxyethyl phthalate, and higher
      alkanes. Tannery effluent extracts were prepared using XAD-4/8 resins,
      dichloromethane, chloroform, and hexane and tested with Ames Salmonella test and
      DNA repair-defective Escherichia coli K-12 mutants. In the presence of XAD
      concentrated tannery effluent, TA98 found to be the most sensitive strain in
      terms of mutagenic index followed by TA97a whereas in terms of mutagenic
      potential TA102 was most responsive. The extracts were also found genotoxic as
      determined in terms of survival of E. coli K-12 mutants, suggesting the presence
      of DNA damaging compounds in the tannery effluents. In the light of results,
      precautious use of tannery effluents for irrigation is suggested.

PMID- 20684993
TI  - Reparation of chlorpyrifos-induced impairment by thyroxine and vitamin C in fish.
AB  - The organophosphate pesticide chlorpyrifos significantly decreased the specific
      activities of catalase (CAT) and lactate dehydrogenase (LDH) in brain, liver,
      gill and skeletal muscle of the freshwater catfish, Heteropneustes fossilis. It
      may be due to binding of the pesticide or its metabolite(s) with the enzyme
      molecules or affecting the synthesis and/or degradation of the enzymes. RNA and
      protein content also declined significantly in different tissues of the fish in
      response to chlorpyrifos, which may be due to alterations in turnover of
      macromolecules involved in protein synthesis. Administration of thyroxine (T4)
      and ascorbic acid (vitamin C) separately or conjointly to chlorpyrifos-exposed
      fish brought CAT, LDH, RNA and protein up to their control levels. The protective
      effect may be attributed to hormone, vitamin and pesticide interaction.
      Therefore, chlorpyrifos-induced impairment in antioxidative, anaerobic and
      protein synthesizing capacity can be repaired by ascorbic acid and T4 in fish.

PMID- 20684994
TI  - Identification of two FoxP3 genes in rainbow trout (Oncorhynchus mykiss) with
      differential induction patterns.
AB  - FoxP3 is a master transcription factor for the development and function of
      regulatory T cells in mammals, but little is known about this molecule in fish.
      Two paralogues of mammalian FoxP3 that share 83.9% identity at the amino acid
      level have been identified in rainbow trout (Oncorhynchus mykiss). The C-terminal
      region containing a Zn_C2H2 domain, a leucine zipper-like domain and a forkhead
      (FH) domain important for dimerization, nuclear translocation, and DNA binding,
      is well conserved between fish and other vertebrate FoxP3. However, the N
      terminal of FoxP3 that is required for FoxP3-mediated repression of transcription
      is greatly diverged between fish, amphibians and monotreme mammals compared to
      eutherian mammals, suggesting that FoxP3 in fish, frog and platypus may have a
      different role to the human and mouse counterpart that defines the Treg cellular
      lineage and mediates the immune regulatory function. The expression of both trout
      (t) FoxP3a and tFoxP3b are detectable in all the 14 tissues examined without any
      significant difference except in muscle in which the expression of tFoxP3a was
      higher. Both tFoxP3a and tFoxP3b are highly expressed in thymus and in immune
      related organs including the spleen, kidney, gills and intestine, and are up
      regulated by phytohaemagglutinin (PHA) in splenocytes and thymocytes. Whilst the
      up-regulated tFoxP3b expression induced by PHA was dose-dependent it required a
      higher PHA concentration to achieve maximal expression relative to tFoxP3a where
      the highest expression level was seen using 1 MUg/ml PHA with higher
      concentrations having no further effects. In addition, the tFoxP3b expression
      increased during development from eyed eggs to fry, when it reached a comparable
      level to that of tFoxP3a. In contrast, tFoxP3a expression was at a high and
      almost constant level over all of the developmental stages examined. The high
      level of tFoxP3a expression in early development may be related to the relatively
      high constitutive level of tFoxP3a expression seen in muscle, perhaps suggesting
      novel roles of tFoxP3 in fish muscle. The structural and expression analysis
      suggests that the tFoxP3a and tFoxP3b are subject to differential modulation of
      expression and may have evolved novel functions. The identification of the two
      trout FoxP3 paralogues will help to clarify the existence of Treg cells and to
      dissect the T cell differentiation pathways in fish.

PMID- 20684995
TI  - Laquinimod interferes with migratory capacity of T cells and reduces IL-17
      levels, inflammatory demyelination and acute axonal damage in mice with
      experimental autoimmune encephalomyelitis.
AB  - We investigated the effect of laquinimod on inflammatory demyelination, axonal
      damage, cytokine profiles and migratory capacities of lymphocytes in C57BL/6 mice
      with active EAE induced with MOG(35-55) peptide. The mice were treated at disease
      induction and after disease onset. Spinal cords were assessed histologically.
      Cytokines and adhesive properties were analyzed in splenocytes. Preventive and
      therapeutic laquinimod treatment reduced clinical signs, inflammation, and
      demyelination. VLA-4-mediated adhesiveness and pro-inflammatory cytokines such as
      IL-17 were down-regulated in treated animals. Within lesions, treated mice showed
      similar axonal densities, but less acute axonal damage than controls. Laquinimod
      might thus protect myelin and axons by decreasing pro-inflammatory cytokines and
      impairing the migratory capacity of lymphocytes.

PMID- 20684996
TI  - The pleasures of play: pharmacological insights into social reward mechanisms.
AB  - Like human children, most young mammals devote a significant amount of time and
      energy playing together, and social play is fun. Although social play is very
      pleasurable, it is more than just a frivolous activity: it is crucial for the
      development of behavioral flexibility, the acquisition of social and cognitive
      competence, and the maintenance of group cohesion. Social play is a natural
      reinforcer, and the neurotransmitter systems intimately implicated in the
      motivational, pleasurable and cognitive aspects of natural and drug rewards, such
      as opioids, endocannabinoids, dopamine and norepinephrine, play an important
      modulatory role in the performance of social play. In this review, we address the
      notion that social play is rewarding, and discuss recent developments in the
      neuropharmacology of this behavior. This provides a framework to understand how
      the brain processes social emotions, to make young individuals enjoy social play.

PMID- 20684997
TI  - Prognostic impact of pre-operative albumin on short-term mortality and
      complications in patients with hip fracture.
AB  - Low serum albumin may have prognostic value for morbidity and mortality in
      patients with hip fracture. The primary aim of the study was to evaluate the
      independent association between low serum albumin (<35 g/l) at hospital admission
      and short-term (in-hospital) mortality and post-operative complications of
      patients with hip fracture. We reviewed a prospective population-based cohort of
      583 hip fracture patients who had pre-operative albumin values measured at
      hospital admission in one of the 3 tertiary hospitals in Northern Alberta,
      Canada. Patients with a primary diagnosis of hip fracture and 65 years or older
      were included. The primary outcomes were in-hospital mortality and any pre
      specified post-operative complication. Mean serum albumin level was 33.8+/-4.5
      g/l (+/-S.D.), and overall 55% (n=318) of patients had a low albumin. The in
      hospital mortality was 8% (n=46) and rate of any non-fatal post-operative
      complication rate was 31/100. Mortality was 11% (n=35) among those with low
      albumin levels and 4% (n=11) for those with normal values (unadjusted odds ratio
      (OR) 2.86, 95% CI=1.42-5.74). After multivariate adjustment, the association
      between low serum albumin and mortality remained large and statistically
      significant (adjusted OR=2.44, 95% confidence interval (CI)=1.17-5.12). Low
      albumin levels were also significantly associated with post-operative medical
      complications (adjusted OR=1.96, 95% CI=1.36-2.83). We conclude that routine
      measurement of serum albumin provides valuable prognostic information for
      treating this frail population.

PMID- 20684998
TI  - The relationship between functional capacity (FC) and cardiac autonomic nervous
      dysfunction to surgery stress in senile patients.
AB  - The aim of the study presented here is to compare the pre- and post-operative
      cardiac autonomic nervous function of senile patients with different functional
      capacities (FC). Ninety-two senile patients scheduled for elective non-cardiac
      surgery were selected, whose FC was evaluated in terms of Duke activity status
      index (DASI). According to FC, the patients were classified into three groups:
      Group 1 (poor FC); Group 2 (moderate FC) and Group 3 (excellent FC). Heart rate
      variability (HRV) was monitored during the night before, on the 1st and the 2nd
      day after operation respectively. The results demonstrated some indices of pre
      operative HRV of patients with poor or moderate FC were significantly lower than
      those with excellent FC. After surgery, total power (TP), high frequency (HF),
      low frequency (LF) and very low frequency (VLF) of all patients were
      significantly decreased. The LF/HF of patients with a poor or moderate FC showed
      a significant difference compared to patients with excellent FC. In conclusion,
      we emphasize that surgery induced a cardiac autonomic nervous dysfunction in
      senile patients not only with low FC but also with high FC; the disturbance of
      pre- and post-operative cardiac autonomic nervous activity is associated with a
      diminished FC (<7METs=metabolic equivalents) in senile patients.

PMID- 20684999
TI  - A comparison of ST elevation versus non-ST elevation myocardial infarction
      outcomes in a large registry database: are non-ST myocardial infarctions
      associated with worse long-term prognoses?
AB  - BACKGROUND: Prognoses in STEMI and NSTEMI beyond one year from onset remain
      unclear. We aimed to compare the treatments and the two-year outcomes in patients
      with myocardial infarction (MI) enrolled at the Polish Registry of Acute Coronary
      Syndromes (PL-ACS). METHODS: A total of 13,441 patients with MI (8250 with STEMI,
      and 5191 with NSTEMI) underwent medical care between October 2003 and June 2005
      in the Silesia region (4.8 million inhabitants). The events analyzed were death,
      MI, stroke and percutaneous (PCI) or surgical (CABG) revascularization. RESULTS:
      After two years, NSTEMI was associated with a higher incidence of death (hazard
      ratio (HR) of 1.09 (95% confidence interval (CI) 1.02-1.17, p<0.0001)); a higher
      incidence of reinfarction, stroke, CABG and a lower rate of PCI. Adjustments for
      baseline characteristics and treatment strategy (invasive vs. non-invasive)
      reversed the HR for mortality and eliminated the difference in MI and stroke. The
      adjusted HR for mortality was 0.76 (95% CI, 0.71-0.83, p<0.0001). STEMI and
      NSTEMI patients treated non-invasively were older and showed higher incidences of
      diabetes, obesity, pulmonary edema and cardiogenic shock than their invasively
      treated counterparts. Invasively treated patients received aspirin, beta
      blockers, ACE inhibitors and statins more often during hospitalization and at
      discharge. CONCLUSIONS: The unadjusted long-term prognosis was worse in NSTEMI.
      After adjustment for the baseline characteristics and treatment strategy, the
      long-term prognosis was worse in STEMI. Patients with MI treated invasively
      showed more favorable clinical characteristics and received guideline-recommended
      therapy more often than patients who did not undergo invasive treatment.

PMID- 20685000
TI  - Isolation and molecular identification of Cronobacter spp. from powdered infant
      formula (PIF) in Bangladesh.
AB  - Cronobacter spp. formerly known as Enterobacter sakazakii is an occasional
      contaminant of powdered infant formula (PIF). This pathogen has been associated
      with out-breaks of a rare form of infant meningitis, necrotizing enterocolitis
      (NEC), bacteremia and neonate deaths. The organism is ranked by the International
      Commission for Microbiological Specifications for Foods (ICMSF) as a 'Severe
      hazard for restricted populations, life threatening or substantial chronic
      sequelae or long duration'. Present study aimed to isolate Cronobacter spp. from
      PIF and clinical samples, such as blood, stool and CSF collected from 93 neonates
      and child patients, age ranged from 0 to 24months. We did not detect Cronobacter
      spp. in any of these samples. Later 32 PIF samples collected from retail markets
      in Bangladesh were tested for the presence of Cronobacter spp. Of these only one
      was found to be contaminated with Cronobacter sp. This is the first case of
      Cronobacter contaminated PIF found in Bangladesh to be reported. The organism was
      successfully identified based on its typical culture characteristics, producing
      blue-green colonies on chromogenic DFI agar and also by a standardized
      conventional PCR assay targeting the alpha glucosidase and 16S rRNA gene sequence
      of Cronobacter sp. The 16S rRNA gene was partially sequenced to provide for the
      phylogenetic analysis of this isolate (DA01) and found to cluster with some other
      Cronobacter isolates in the phylogram.

PMID- 20685001
TI  - Are breast cancer navigation programs cost-effective? Evidence from the Chicago
      Cancer Navigation Project.
AB  - OBJECTIVES: One of the aims of the Chicago Cancer Navigation Project (CCNP) is to
      reduce the interval of time between abnormal breast cancer screening and
      definitive diagnosis in patients who are navigated as compared to usual care. In
      this article, we investigate the extent to which total costs of breast cancer
      navigation can be offset by survival benefits and savings in lifetime breast
      cancer-attributable costs. METHODS: Data sources for the cost-effectiveness
      analysis include data from published literature, secondary data from the NCI's
      Surveillance Epidemiology and End Results (SEER) program, and primary data from
      the CCNP. RESULTS: If women enrolled in CCNP receive breast cancer diagnosis
      earlier by 6 months as compared to usual care, then navigation is borderline cost
      effective for $95,625 per life-year saved. Results from sensitivity analyses
      suggest that the cost-effectiveness of navigation is sensitive to: the interval
      of time between screening and diagnosis, percent increase in number of women who
      receive cancer diagnosis and treatment, women's age, and the positive predictive
      value of a mammogram. CONCLUSIONS: In planning cost-effective navigation
      programs, special considerations should be made regarding the characteristics of
      the disease, program participants, and the initial screening test that determines
      program eligibility.

PMID- 20685002
TI  - How ephedrine escaped regulation in the United States: a historical review of
      misuse and associated policy.
AB  - OBJECTIVE: Ephedrine is not only efficacious in the treatment of numerous
      ailments, but also has a long history of misuse. Research was needed to examine
      ephedrine policy over time in order to determine potential regulatory flaws that
      allowed misuse to continue. METHODS: This review is based on primary literature
      derived from systematic searches of historical and scientific archives, as well
      as grey literature. RESULTS: Ephedrine managed to pass through numerous
      regulatory loopholes within seventy years. Despite warnings of misuse over the
      latter half of the century, ephedrine, and its herbal source, ephedra, were
      regulated in a piecemeal fashion and remained easily available to the public.
      Health authorities have struggled to control ephedrine, as an amphetamine "look
      alike," as a methamphetamine precursor, as a dietary supplement, and as a
      medication. Despite being a potentially dangerous stimulant, under-regulation was
      perhaps more problematic than the substance itself. CONCLUSIONS: Tighter control
      of all ephedrine products, drugs and dietary supplements alike, might have
      prevented adverse outcomes and allowed this substance to remain available in a
      safer manner. Stringent regulation of all ephedrine products is necessary to
      prevent misuse and to protect the public's health.

PMID- 20685003
TI  - Patients' attitudes towards generic drug substitution in Japan.
AB  - OBJECTIVE: The aim of this study was to evaluate the understanding and attitude
      of Japanese patients towards generic drug substitutions. METHOD: The subjects
      were male and female patients, who purchased their prescription medications at a
      pharmacy. A questionnaire was created to assess their attitudes towards generic
      drugs. RESULTS: Of 1215 respondents, 68.4% knew the term "generic drugs." The
      majority of them had the correct understanding only on the following two points:
      generic drugs are less expensive than the brand name drugs (86.0%) and generic
      drugs contain the same active ingredients as brand name drugs (71.1%). However,
      their understanding was poor in other aspects of generic substitution: the
      availability and accessibility of generic drugs, etc. Only the experience of a
      previous generic drug substitution was significantly associated with the
      increased willingness for generic substitution (OR=2.93, CI 1.93-4.44). The main
      reasons for accepting generic substitutions were recommendations by physicians
      (48.6%) and by pharmacists (33.1%). CONCLUSION: The public awareness program on
      generic drugs should be expanded to include more detailed information so that
      patients obtain the correct understanding of generic substitution. It is critical
      that physicians and pharmacists have the proper understanding of generic drug
      substitution and provide the correct information to patients.

PMID- 20685004
TI  - Universal health care in Thailand: concerns among the health care workforce.
AB  - OBJECTIVE: To investigate the impact of the universal health care policy from the
      perspective of Thai health care professionals. METHODS: Semi-structured
      interviews with purposively selected health care professionals and key
      informants. RESULTS: Health care professionals at public hospitals, particularly
      in rural areas, have experienced up to a doubling in the number of daily out
      patients; many with superficial symptoms. While the improved access to health
      care provisions was welcomed, questions regarding the appropriateness of seeking
      medical advice were raised. Concern regarding equity: between the universal
      health care policy and two parallel public health cover schemes; rural and urban
      areas; and the public and private sector also emerged. There are potentials for
      health care professionals to congregate in the private sector and urban areas
      where workloads are perceived to be less demanding. CONCLUSIONS: The general
      perception of the health care professionals interviewed suggests that although
      increased access and health equity was welcomed, this policy has had undesired
      effects and exacerbated rural-urban and public-private tensions. Universal
      coverage increased access to health care. However, equity may be further enhanced
      by consolidating the three public health covers into a single scheme and develop
      a parallel private income protection insurance scheme.

PMID- 20685005
TI  - An evaluation of the policy on community health organizations in China: will the
      priority of new healthcare reform in China be a success?
AB  - OBJECTIVES: The objective of this paper is to assess historical and recent health
      reform efforts in China. We provide a brief history of the Chinese healthcare
      system since 1949 as context for the current healthcare; examine the factors that
      led to recent efforts to reestablish community-based care in China; and identify
      the challenges associated with attaining a sustainable and quality community
      healthcare system. METHODS: Based on literature review and publicly available
      data in China, the paper will present a historical case study analysis of health
      policy change of CHOs in China and provide policy evaluation, and the paper
      provided policy suggestions. RESULTS: We find that the government's recent
      efforts to emphasize the significance of community healthcare services in China
      have started to change patterns of healthcare use, but many problems still
      inhibit the development of CHOs, including unsustainable governmental roles,
      issues of human resource inadequacy and laggard GP practice, poorly designed
      payment schemes, patient's trust crisis and continue to inhibit the development
      of community-based primary care. CONCLUSIONS: Additional policy efforts to help
      CHOs' development are needed. Recent government investments in public health and
      primary care alone are not sufficient and could not be sustainable. It will not
      until long-term self-sustaining mechanisms to relieve an omnipotent government
      are established, including competent community doctors (GP) system, supportive
      social insurance reimbursement, appropriate financial incentives to providers,
      better transparency and accountability, as well as a more regulated referral
      system, a legitimate, sustainable and quality community health system could be
      attained.

PMID- 20685006
TI  - Causes and evolutionary significance of genetic convergence.
AB  - Convergent phenotypes provide extremely valuable systems for studying the
      genetics of new adaptations. Accumulating studies on this topic have reported
      surprising cases of convergent evolution at the molecular level, ranging from
      gene families being recurrently recruited to identical amino acid replacements in
      distant lineages. Together, these different examples of genetic convergence
      suggest that molecular evolution is in some cases strongly constrained by a
      combination of limited genetic material suitable for new functions and a
      restricted number of substitutions that can confer specific enzymatic properties.
      We discuss approaches for gaining further insights into the causes of genetic
      convergence and their potential contribution to our understanding of how the
      genetic background determines the evolvability of complex organismal traits.

PMID- 20685008
TI  - In situ oxidation and associated mass-flux-reduction/mass-removal behavior for
      systems with organic liquid located in lower-permeability sediments.
AB  - The effectiveness of permanganate for in situ chemical oxidation of organic
      liquid (trichloroethene) trapped in lower-permeability (K) zones located within a
      higher-permeability matrix was examined in a series of flow-cell experiments. The
      permanganate solution was applied in both continuous and pulsed-injection modes.
      Manganese-oxide precipitation, as confirmed by use of SEM-EDS, occurred within,
      adjacent to, and downgradient of the lower-K zones, reflective of trichloroethene
      oxidation. During flow interruptions, precipitate formed within the surrounding
      higher-permeability matrix, indicating diffusive flux of aqueous-phase
      trichloroethene from the lower-K zones. The impact of permanganate treatment on
      mass flux behavior was examined by conducting water floods after permanganate
      injection. The results were compared to those of water-flood control experiments.
      The amount of water flushing required for complete contaminant mass removal was
      reduced for all permanganate treatments for which complete removal was
      characterized. However, the nature of the mass-flux-reduction/mass-removal
      relationship observed during water flooding varied as a function of the specific
      permanganate treatment.

PMID- 20685009
TI  - Association of serotonin and dopamine gene pathways with behavioral subphenotypes
      in dementia.
AB  - Genetic association studies investigating the association between genes of
      serotonergic and dopaminergic systems and behavioral and psychological symptoms
      in dementia (BPSD) are contradictory. We have utilized 1008 probable Alzheimer's
      disease (AD) patients from the UK and used the 12-item Neuropsychiatric
      Inventory. We applied a multiple indicators-multiple causes (MIMIC) approach to
      investigate the effect of 11 polymorphisms on the 4 behavioral subphenotypes
      "psychosis", "moods", "agitation", and "behavioural dyscontrol". Significant
      associations were observed between the serotonin transporter gene (SERT)
      polymorphism STin2 and "psychosis"; the dopamine transporter gene (DAT) 3'
      variable number tandem repeats (VNTR) and "agitation"; and the dopamine receptor
      4 (DRD4) VNTR and "moods" factors. Direct associations were identified between
      the dopamine receptor 3 (DRD3) BalI polymorphism and depression; the dopamine
      receptor 1 (DRD1) and dopamine transporter gene 3' VNTR polymorphisms and
      aberrant motor behavior; the DRD4 VNTR and sleep disturbances; and the SERT gene
      VNTR 5HTTLPR and apathy items. Significant interactions observed between
      polymorphisms suggested epistatic effects and interactions between polymorphisms
      and medications highlighted potential treatment response. This multiple
      indicators multiple causes (MIMIC) model efficiently captured the complexity of
      the interrelations between genetic variation, behavioral symptoms, and clinical
      variables.

PMID- 20685010
TI  - [Prolonged fever and jaundice in a patient with alcoholic liver disease].
AB  - We report the case of a 40-year-old man with underlying alcoholic liver disease
      who presented with prolonged fever, jaundice and liver failure associated with
      Coxiella burnetii infection. After diagnosis and appropriate antibiotic
      treatment, the patient made a complete recovery. We describe aspects of this case
      and provide a practical review of the literature on the topic. We also discuss
      the importance of this infection and the need for its inclusion in the
      differential diagnosis of this clinical picture.

PMID- 20685011
TI  - [Diagnosis and treatment of catatonia in the elderly].

PMID- 20685012
TI  - [Cultural competence as a tool for the healthcare of the immigrant population].

PMID- 20685013
TI  - [Research on social determinants of health and health inequalities: evidence for
      health in all policies].
AB  - This article aims to review conceptual frameworks and some principles to be
      considered in research on social determinants of health and health inequalities.
      Some indicators of research on these issues in Spain are described. General
      expenditure on research and development in Spain is far from the Organisation for
      Economic Co-operation and Development mean. In addition, both globally and within
      Spain, the scientific production on health inequalities is very low, especially
      compared with other research areas. The budget for research on health
      inequalities is also reduced. A striking example is provided by analysis of the
      projects funded by the Marato de TV3, which seems to have little interest in
      funding research on health inequalities. However, both the scientific production
      and project financing on health inequalities have increased in the last decade.
      Finally, to advance research on health inequalities and its contribution to the
      incorporation of health in all policies, recommendations are made, which include
      redefining priorities, ensuring resources and promoting knowledge translation.

PMID- 20685014
TI  - "If you haven't got a PhD, you're not going to get a job": the PhD as a hurdle to
      continuing academic employment in nursing.
AB  - This paper is drawn from a larger study that sought to identify and examine
      issues around the employment of sessional academic staff in baccalaureate nurse
      education. Twelve sessional teachers and 12 continuing academics participated in
      the interviews. Examination of the data revealed the PhD was perceived as a
      hurdle to continuing employment in nurse education in the university sector. In
      the current climate, sessional teachers continue to be an essential part of the
      nursing academic workforce and are necessary to meet the teaching and learning
      demands associated with implementing nursing curricula. Findings suggest a need
      for scrupulous processes in relation to the recruitment of sessional staff, and
      highlight the difficulties that sessional teachers may have in securing
      continuing academic employment. We provide recommendations to facilitate the
      appointment of appropriate individuals into sessional roles and highlight the
      need to mentor and support sessional teachers wishing to pursue a career as nurse
      academics. Questions are raised about how nursing can plan for future academic
      workforce needs in a context of an aging academic workforce, the demand for
      doctoral training for nurse academics, and widespread casualisation of the
      nursing academic workforce.

PMID- 20685015
TI  - Differential metabolic effects of casein and soy protein meals on skeletal muscle
      in healthy volunteers.
AB  - BACKGROUND & AIMS: Dietary protein intake is known to affect whole body and
      interorgan protein turnover. We examined if moderate-nitrogen and carbohydrate
      casein and soy meals have a different effect on skeletal muscle protein and amino
      acid kinetics in healthy young subjects. METHODS: Muscle protein and amino acid
      kinetics were measured in the postabsorptive state and during 4-h enteral intake
      of isonitrogenous [0.21 g protein/(kg body weight. 4 h)] protein-based test
      meals, which contained either casein (CAPM; n = 12) or soy protein (SOPM; n = 10)
      in 2 separate groups. Stable isotope and muscle biopsy techniques were used to
      study metabolic effects. RESULTS: The net uptake of glutamate, serine, histidine,
      and lysine across the leg was larger during CAPM than during SOPM intake. Muscle
      concentrations of glutamate, serine, histidine, glutamine, isoleucine and BCAA
      changed differently after CAPM and SOPM (P < 0.05). Muscle net protein breakdown
      decreased significantly (P < 0.05) to zero during feeding of both CAPM and SOPM,
      but differences in their (net) breakdown rates were not significant. Muscle
      protein synthesis was not different between CAPM and SOPM. CONCLUSION: Moderate
      nitrogen casein and soy protein meals differently alter leg amino acid uptake
      without a significant difference in influencing acute muscle protein metabolism.

PMID- 20685016
TI  - Hurdles and opportunities for newborn care in rural Uganda.
AB  - INTRODUCTION: A set of evidence-based delivery and neonatal practices have the
      potential to reduce neonatal mortality substantially. However, resistance to the
      acceptance and adoption of these practices may still be a problem and challenge
      in the rural community in Uganda. OBJECTIVES: To explore the acceptability and
      feasibility of the newborn care practices at household and family level in the
      rural communities in different regions of Uganda with regards to birth asphyxia,
      thermo-protection and cord care. METHODS: A qualitative design using in-depth
      interviews and focus group discussions were used. Participants were purposively
      selected from rural communities in three districts. Six in-depth interviews
      targeting traditional birth attendants and nine focus group discussions composed
      of 10-15 participants among post childbirth mothers, elderly caregivers and
      partners or fathers of recently delivered mothers were conducted. All the mothers
      involved has had normal vaginal deliveries in the rural community with unskilled
      birth attendants. Latent content analysis was used. FINDINGS: Two main themes
      emerged from the interviews: 'Barriers to change' and 'Windows of opportunities'.
      Some of the recommended newborn practices were deemed to conflict with
      traditional and cultural practices. Promotion of delayed bathing as a thermo
      protection measure, dry cord care were unlikely to be accepted and spiritual
      beliefs were attached to use of local herbs for bathing or smearing of the baby's
      skin. However, several aspects of thermo-protection of the newborn, breast
      feeding, taking newborns for immunisation were in agreement with biomedical
      recommendations, and positive aspects of newborn care were noticed with the
      traditional birth attendants. CONCLUSIONS: Some of the evidence based practices
      may be accepted after modification. Behaviour change communication messages need
      to address the community norms in the country. The involvement of other newborn
      caregivers than the mother at the household and the community early during
      pregnancy may influence change of behaviour related to the adoption of the
      recommended newborn care practices.

PMID- 20685017
TI  - Editorial. Emerging contaminants.

PMID- 20685018
TI  - Occurrence of PAH in the seasonal snowpack of the Eastern Italian Alps.
AB  - PAH concentrations have been determined in 47 seasonal snowpack samples collected
      in the Valbelluna valley and in the Bellunesi Dolomites National Park, in the
      Italian North-Eastern Alps, during the winter of 2005. The SigmaPAH concentration
      in high-altitude alpine sites (above 1700 m) was 32+/-20 ng/kg while in valley
      bottom urban areas it was 165+/-54 ng/kg with maximum values of 290 ng/kg. The
      GIS mapping technique was employed to produce a PAH spatial distribution. The
      urbanized Valbelluna valley, and in particular the SW part, had the highest
      accumulation of all PAH, with values an order of magnitude more than those in
      rural and alpine areas. This behaviour is consistent with urban air quality data,
      and is due to geo-morphological and meteorological factors such as the deeper
      shape of the valley at the position of the town of Feltre and the low altitude of
      the boundary layer during the winter season.

PMID- 20685019
TI  - Cervical cancer screening in Malaysia: Are targeted interventions necessary?
AB  - This study examines the determinants of Papanicolaou Smear Test (PST) screening
      for cervical cancer among women in Malaysia. Attention is focused on the reasons
      different population subgroups give for non-screening. We find that Indian women
      are the least likely to have had a PST and also the least likely to know the
      reasons why one is screened. Malay women are less likely than Chinese women to
      have received a PST and are more likely to report embarrassment as the reason for
      not being tested. Urban women are less likely than rural women to have been
      tested and more likely to state lack of time as the reason. These results suggest
      targeted interventions may be necessary to increase screening rates in Malaysia.

PMID- 20685020
TI  - Reactions to Fair Society, Healthy Lives (the Marmot Review).

PMID- 20685021
TI  - Application of platysma-based transpositional flap for through-and-through facial
      defect when the facial artery circulation is blocked or compromised.
AB  - PURPOSE: A novel use of site-limited platysma-based transpositional flap is
      demonstrated and discussed for the reconstruction of facial defects. MATERIALS
      AND METHODS: Between January 1985 and January 2001, 342 patients were operated on
      for advanced oral-oropharyngeal and orofacial cancers. In 6 cases, a platysma
      based transpositional flap was used for external closure of facial through-and
      through defects. Internally, the saved oral mucosa was used in 4 patients and
      fasciocutaneous forearm free flaps in 2 patients. The facial artery was blocked
      in all cases. RESULTS: The postoperative course was uneventful except in 1 case,
      when partial loss of the flap was observed intraorally. The externally used
      transpositional platysma-based flap showed cosmetic and functional advantages:
      its consistency, color, and texture were similar to those of the original facial
      tissues, the area of operation was the same, and the donor site was closed
      primarily. CONCLUSION: The site-limited platysma-based myocutaneous
      transpositional flap is usable and safe even in those cases in which circulation
      of the facial artery is damaged or local vascular compromise has occurred and the
      facial through-and-through defect is extended. The facial reconstruction
      described is one of several applicable reconstructive methods that may be chosen
      for special facial defects. The method is not applicable when the neck is
      radically operated on (radical neck dissection) and/or irradiated. No similar use
      of platysma-based transpositional flaps has been reported thus far.

PMID- 20685022
TI  - Anterior dislocation of the intact mandibular condyle caused by fracture of the
      articular eminence: an unusual fracture of the temporomandibular joint apparatus.

PMID- 20685023
TI  - Maxillary fragment stabilization after Le Fort I fracture with 1 screw pair per
      plate.
AB  - PURPOSE: The aim of the present study was to determine whether plates with only 1
      screw pair can be used for Le Fort I fracture management. Good postoperative
      results motivated the direct application of mandible fixation principles to the
      fractured midface region without additional experimental research. However, the
      amount and distribution of the forces in the midface region is different from
      those on the mandible. MATERIALS AND METHODS: Testing was conducted on plastic
      anatomic models. The validity of the experimental model was tested before the
      fixation techniques were compared. Standard miniplates and miniscrews were used
      for fixation of the maxilla. The model surface strain analysis was conducted
      using the noncontact object grating method, which enabled the surface strain
      measurement without direct influence on the measured model. RESULTS: In 2 screw
      pair fixation, the outer screw pair has little effect on the local strain
      distribution, but it lowers the contact forces along the crack. One screw pair
      fixation is stable enough for fixation, but it has a greater strain peak at the
      crack edges. CONCLUSION: Our results showed that 1 screw pair per plate was
      enough for stable fixation, and 2 or more screw pairs should only be used when
      the bone fragment at the fracture site cannot sufficiently transmit forces along
      the crack.

PMID- 20685024
TI  - [Resected asymptomatic intrathoracic textiloma 37 years after thoracotomy].

PMID- 20685025
TI  - Th1 and th2 cytokine expression in nasopharyngeal secretions during acute
      bronchiolitis in children younger than two years old.
AB  - OBJECTIVES: We characterised the T helper cytokine profiles on the surface of
      nasal mucosa of children with acute bronchiolitis caused by Respiratory Syncytial
      Virus, Parainfluenza Virus, Influenza Virus, Adenovirus, or without any viral
      identification, in order to examine whether these viral types modified cytokine
      responses. As an additional objective we sought to determine if T helper
      polarisation was associated with other demographic and environmental factors.
      METHODS: A prospective study of children with acute bronchiolitis was performed.
      Patients were recruited from the emergency department of a central hospital in
      Lisbon, Portugal. Demographical, epidemiological and clinical data were gathered
      from a questionnaire. Nasal swabs were collected for viral studies
      (immunofluorescence) and T cell cytokine responses (detection of expression of
      interleukins 4, 13, 12 and interferon-gamma by real-time polymerase chain
      reaction assays). RESULTS: Respiratory Syncytial Virus elicited lower levels of
      interleukin 4, when compared with samples without virus identification. A similar
      tendency to Th1 polarisation was found in older children, in those who attended
      day-care centres, and in breastfed individuals. Exposure to tobacco smoke was
      associated with a Th2 bias in this population. CONCLUSIONS: These findings show
      that Respiratory Syncytial Virus infection contributes to Th1 polarisation in
      immune response of respiratory mucosa, an effect that is similar to other
      environmental factors. Further studies are needed to assess immune response to
      other infectious causes of acute bronchiolitis.

PMID- 20685026
TI  - Single-port laparoscopic myomectomy using transumbilical GelPort access.
AB  - OBJECTIVE: To describe our initial experience with single-port laparoscopic
      myomectomy (SP-LM) using transumbilical GelPort access and the surgical technique
      used, and to evaluate the safety and feasibility of this procedure. STUDY DESIGN:
      A prospective observational study was performed at a university teaching hospital
      from January 2009 to December 2009. Fifteen patients with symptomatic subserosal
      or superficial intramural myomas (<= 8 cm) underwent SP-LM. RESULTS: The mean age
      and body mass index were 35.0 +/- 8.6 years and 22.6 +/- 2.6 kg/m2. Two patients
      had a history of previous abdominal surgery, consisting of one and two cesarean
      deliveries. The mean operating time, hemoglobin change, return of bowel activity,
      and length of hospital stay were 81 +/- 21.5 min, 1.1 +/- 0.5 g/dL, 34.3 +/- 5.9
      h, and 3.1 +/- 0.5 days, respectively. In one patient (6.7%), SP-LM was converted
      to two-port LM. There were no surgical or wound complications in any patient, and
      the histopathological result was leiomyoma in all the cases. CONCLUSION: SP-LM is
      feasible in selected patients with symptomatic myoma.

PMID- 20685027
TI  - Genetic variations in vascular endothelial growth factor but not in angiotensin I
      converting enzyme genes are associated with endometriosis in Estonian women.
AB  - OBJECTIVE: To determine plausible associations between endometriosis and vascular
      endothelial growth factor gene (VEGF -2578 A/C, -1154 G/A, -634 G/C and 936 C/T),
      also angiotensin I-converting enzyme gene (ACE -240 A/T and 2350 A/G) single
      nucleotide polymorphisms (SNPs), as well as their respective haplotypes. STUDY
      DESIGN: PCR-based restriction fragment length polymorphism analysis was used to
      detect SNPs in VEGF and ACE genes in 150 Estonian women with endometriosis and
      199 control subjects. RESULTS: The CC genotype of the VEGF -2578 A/C SNP was
      correlated with a decreased risk of endometriosis (OR=0.40, 95% CI 0.20-0.78).
      Other VEGF and ACE SNPs and haplotypes were not associated with endometriosis.
      CONCLUSION: This case-control study demonstrated that the VEGF -2578 A/C SNP may
      influence susceptibility to endometriosis in the Estonian population, while
      associations between endometriosis and other VEGF and ACE SNPs, as well as the
      respective haplotypes are unlikely.

PMID- 20685028
TI  - C. albicans activates cyclooxygenase but not its product prostaglandin E2in HPV
      16-stabilized cells.
AB  - OBJECTIVE: The selective induction of cyclooxygenase-2 (COX-2) in human cells by
      Candida albicans was the first report of its role in infectious disease. This led
      us to question whether recurrent vulvovaginal candidosis in the cancer patient is
      involved in the formation of malignant tumors of the genital tract. Our
      speculation coincided with the patients' assessments in our hospital, where few
      cancer patients had a prior history of Candida infection. We wanted to study the
      contribution of C. albicans to gynecological cancers. STUDY DESIGN: In the
      present study, we used the developed vaginal epithelial cells system, having an
      insertion of HPV 16 viral sequence, as a model system (VK2/E6E7) to investigate
      the effect of Candida infection on prostaglandin E2 synthesis, which is known to
      be associated with cancers. We infected VK2/E6E7 cells with wild-type C. albicans
      and determined its effect on COX-2 and prostaglandin E2 synthesis, and its
      alteration in dependence on p53, and we analyzed the ubiquitin-proteasome
      degradation pathways and the involvement of 14-3-3 protein, which is involved in
      the modulation of the cell cycle. RESULTS: Our work using the cellular model
      indicates that recurrent Candida infection of the genital tract in patients
      carrying HPV 16 viral infection blocks the proliferation of host cells, PGE2
      synthase expression and thus PGE2 production. CONCLUSION: We found that Candida
      infection contributes only to cell cycle arrest and does not by itself contribute
      actively to the development of cancer, although it is associated with patients
      diagnosed as having cancer of the genital tract induced by HPV 16 virus.

PMID- 20685029
TI  - Expression of matrix metalloproteinase-2 and tissue inhibitors of
      metalloproteinase-1 (TIMP-1, TIMP-2 and TIMP-3) in women with uterine prolapse
      but without urinary incontinence.
AB  - OBJECTIVE: To investigate the activities of matrix metalloproteinase-2 (MMP-2)
      and its inhibitors, tissue inhibitor of metalloproteinase-1, -2 and -3 (TIMP-1,
      TIMP-2 and TIMP-3), in the pelvic support and nonsupport tissue of women with
      uterine prolapse but without urinary incontinence. STUDY DESIGN: Paired samples
      of uterosacral ligament and cervical tissue were obtained from 11 postmenopausal
      and 8 premenopausal women with severe uterine prolapse. Nine premenopausal women
      without prolapse were selected as normal controls. Immunoreactivity of MMP-2 and
      TIMPs was demonstrated by immunohistochemistry. Steady state of MMP-2 as well as
      TIMPs messenger RNA (mRNA) expression was analyzed by polymerase chain reaction
      (PCR) with quantitative expression determined by multiplex PCR. RESULTS: A
      significantly higher expression of MMP-2 mRNA and lower expression of TIMP-2 mRNA
      were found in uterosacral ligament in uterine prolapse women compared to
      controls. In the cervical tissue, however, the MMP-2 and TIMPs mRNA expression
      was comparable between prolapse and control groups. With regard to menopausal
      status, there was no significant difference in MMP-2 and TIMPs mRNA expression
      between premenopausal and postmenopausal women with uterine prolapse.
      CONCLUSIONS: An increase in MMP-2 mRNA and a decrease in TIMP-2 mRNA expression
      in uterosacral ligament are related to uterine prolapse in women without urinary
      incontinence.

PMID- 20685030
TI  - Rhizospheric bacteria alleviate salt-produced stress in sunflower.
AB  - The effect of isolate Pseudomonas fluorescens biotype F and P. fluorescens CECT
      378(T) inoculation on fresh weight and ions accumulation was studied in sunflower
      plants grown in sand:peat substrate with addition of 100mM NaCl. The inoculation
      resulted in an increase in fresh weight of more than 10% in salt treatments and
      in an accumulation of less Na(+) and more K(+) in plant tissues in all cases. The
      bacterial inoculants favoured the K(+)/Na(+) ratio in all plant parts and in the
      case of the isolate CECT 378(T) conducted to 66% increment in leaves, 34% in
      stems and 16% in roots, while the effect of isolate inoculation was (only) more
      evident in leaves and stems with 30% and 26%, respectively. Both strains were
      found to produce indoleacetic acid and siderophores in in-vitro tests, thus the
      production of indoles was highly dependent on the exogenous tryptophan in the
      medium. The results suggest that salt stress in sunflower plants was alleviated
      partially by the inoculation with strains that produce indoles and siderophores,
      having also a positive effect on the K(+)/Na(+) ratio in the shoot. Moreover,
      those plants were characterized with better-developed roots.

PMID- 20685032
TI  - The role of the prostate cancer antigen 3 (PCA3) test for the diagnosis of
      prostate cancer in the era of opportunistic prostate-specific antigen screening.

PMID- 20685033
TI  - Chronic immune-mediated demyelinating polyneuropathy in the setting of cetuximab
      treatment.
AB  - Cetuximab, a chimeric mouse/human monoclonal antibody directed against the
      epidermal growth factor receptor, is commonly used in colorectal and head and
      neck cancer. We describe an acquired neuropathy associated with cetuximab
      treatment in a patient with squamous cell carcinoma of the tongue. Our patient
      was treated with cetuximab from May to July 2008. In December 2008, he first
      noticed numbness in his feet. He progressed over the next 5 months to develop
      weakness in both legs, a lack of sensation up to his knees, pain in the dorsum of
      his feet with a burning sensation, and difficulty ambulating to the point of
      requiring a walker. He also had numbness in his fingertips and was unable to use
      his hands for fine movements. Electrodiagnostic studies demonstrated prolonged
      distal latencies, conduction block, and prolonged F-wave latencies, consistent
      with a diagnosis of definite CIDP according to EFNS/PNS criteria. Low amplitude
      potentials were noted in nerves of the lower extremities, indicative of secondary
      axonal loss. Extensive workup for an alternative cause was negative. He improved
      clinically after IVIG and corticosteroid treatment. We cannot strongly establish
      a causal relationship in this case, as 5 months elapsed between cetuximab
      treatment and the onset of neuropathic symptoms. Nonetheless, clinical vigilance
      is recommended when evaluating patients for neuropathy who have received
      cetuximab.

PMID- 20685034
TI  - Surgical resection of osteolytic calvarial lesions: clinicopathological features.
AB  - OBJECTIVE: Osteolytic calvarial lesions are infrequent findings. Some cases are
      found incidentally during cancer staging or subsequent to unspecific symptoms.
      There are no standardized algorithms for the treatment of such lesions. Thus, the
      aim of this study was to describe the clinicopathological features and surgical
      outcome in various osteolytic calvarial lesions. MATERIAL AND METHODS: The
      clinical presentation, radiological imaging findings, surgical treatment and
      histopathological findings of 36 patients who underwent surgery for an osteolytic
      calvarial lesion at our institution between 1998 and 2008 were reviewed. RESULTS:
      Thirty-six osteolytic calvarial lesions were identified in 20 men and 16 women.
      Mean age at diagnosis was 37 years. Ten patients were children younger than 15
      years. Five lesions were detected during cancer staging. Complete removal of the
      calvarial lesions was achieved in all patients without complications. The most
      common histopathological diagnosis was metastasis (n=9), Langerhans-cell
      histiocytosis (n=9), and intraosseous hemangioma (n=5). In two asymptomatic
      patients, histopathological findings revealed metastases of a previously unknown
      tumor. In two other patients known to suffer from cancer, histopathological
      findings indicated intraosseous hemangioma and intraosseous meningioma,
      respectively. Reconstruction of the calvarial defect was performed in 24 cases
      with poly-methyl-methacrylate and with titanium mesh in 1 case. CONCLUSIONS:
      Osteolytic calvarial lesions can be found in any age group. The histopathological
      examination reveals various entities, and in some instances it was not concurrent
      with a primary malignancy. Because surgical morbidity is low, we recommend
      complete resection of osteolytic calvarial lesions with reconstruction when
      feasible.

PMID- 20685035
TI  - Antagonists of IAP proteins as cancer therapeutics.
AB  - Inhibitor of apoptosis (IAP) proteins play pivotal roles in cellular survival by
      blocking apoptosis, modulating signal transduction, and affecting cellular
      proliferation. Through their interactions with inducers and effectors of
      apoptosis IAP proteins can effectively suppress apoptosis triggered by diverse
      stimuli including death receptor signaling, irradiation, chemotherapeutic agents,
      or growth factor withdrawal. Evasion of apoptosis, in part due to the action of
      IAP proteins, enhances resistance of cancer cells to treatment with
      chemotherapeutic agents and contributes to tumor progression. Additionally, IAP
      genes are known to be subject to amplification, mutation, and chromosomal
      translocation in human malignancies and autoimmune diseases. In this review we
      will discuss the role of IAP proteins in cancer and the development of
      antagonists targeting IAP proteins for cancer treatment.

PMID- 20685036
TI  - Targeting apoptosis pathways in cancer by Chinese medicine.
AB  - The traditional Chinese medicine (TCM) uses a combination of different natural
      products based on practical experiences. To better understand the therapeutic
      functions of TCM, large efforts have been made to identify the principle
      constituents of TCM and to unravel the molecular mechanisms behind the efficacy
      observed. This review aims to summarize research results obtained from the most
      intensively studied TCM phytochemical compounds namely the alkaloids Berberine,
      Evodiamine; anthraquinones Emodin, Aloe-emodin, Rhein; the terpenoids
      Artemisinin, Celastrol, Triptolide; the flavones Apigenin, Chrysin, Wogonin,
      Baicalein; and the cyclopenta[b]benzofuran derivatives Rocaglamide. Most of them
      have been originally identified as anti-inflammatory and anti-viral reagents and
      are now known to also possess anti-tumor activities by targeting the apoptosis
      pathways in cancer. This review also intends to give an overview of the
      mechanisms of action identified so far. These breakthrough findings may have
      important implications for targeted-cancer therapy and for modernization of TCM.

PMID- 20685037
TI  - Bioremediation of crude oil-contaminated soil: comparison of different
      biostimulation and bioaugmentation treatments.
AB  - Biostimulation with inorganic fertilizer and bioaugmentation with hydrocarbon
      utilizing indigenous bacteria were employed as remedial options for 12 weeks in a
      crude oil-contaminated soil. To promote oil removal, biocarrier for
      immobilization of indigenous hydrocarbon-degrading bacteria was developed using
      peanut hull powder. Biodegradation was enhanced with free-living bacterial
      culture and biocarrier with a total petroleum hydrocarbon removal ranging from
      26% to 61% after a 12-week treatment. Oil removal was also enhanced when peanut
      hull powder was only used as a bulking agent, which accelerated the mass transfer
      rate of water, oxygen, nutrients and hydrocarbons, and provided nutrition for the
      microflora. Dehydrogenase activity in soil was remarkably enhanced by the
      application of carrier material. Metabolites of polycyclic aromatic hydrocarbons
      were identified by Fourier transform ion cyclotron resonance mass spectrometry.

PMID- 20685038
TI  - Study on the treatment of 2-sec-butyl-4,6-dinitrophenol (DNBP) wastewater by ClO2
      in the presence of aluminum oxide as catalyst.
AB  - The chlorine dioxide (ClO(2)) oxidative degradation of 2-sec-butyl-4,6
      dinitrophenol (DNBP) in aqueous solution was studied in detail using Al(2)O(3) as
      a heterogeneous catalyst. The operating parameters such as the ClO(2)
      concentration, catalyst dosage, initial DNBP concentration, reaction time and pH
      were evaluated. Compared with the conventional ClO(2) oxidation process without
      the catalyst, the ClO(2) catalytic oxidation system could significantly enhance
      the degradation efficiency. Under the optimal condition (DNBP concentration 39 mg
      L(-1), ClO(2) concentration 0.355 g L(-1), reaction time 60 min, catalyst dosage
      10.7 g L(-1) and pH 4.66), degradation efficiency approached 99.1%. The catalyst
      was used at least 8 cycles without any appreciable loss of activity. The kinetic
      studies revealed that the ClO(2) catalytic oxidation degradation of DNBP followed
      pseudo-first-order kinetics with respect to DNBP concentration. The ClO(2)
      catalytic oxidation process was found to be very effective in the decolorization
      and COD(Cr) reduction of real wastewater from DNBP manufacturing. Thus, this
      study showed potential application of ClO(2) catalytic oxidation process in
      degradation of organic contaminants and industrial effluents.

PMID- 20685039
TI  - Adsorption of nitrobenzene from aqueous solution on activated sludge modified by
      cetyltrimethylammonium bromide.
AB  - A novel method was conducted to modify activated sludge with
      cetyltrimethylammonium bromide (CB) to obtain an adsorbent to remove aqueous
      nitrobenzene. The adsorption characteristics of nitrobenzene onto modified
      activated sludge (MAS) were investigated, by contrast with those of unmodified
      activated sludge (UMAS). Nitrobenzene adsorption onto MAS is more favorable than
      that of UMAS at initial nitrobenzene concentrations below 150 mg/L, above which
      they have an equivalent adsorption capacity. pH value has a significant influence
      on the adsorption capacity, especially from 10.0 to 12.6 for MAS and from 9.0 to
      11.0 for UMAS. The modification changes the steady even surface of activated
      sludge into uneven one, which is better for adsorption. The hydroxyl of activated
      sludge and hydrophobic group of CB adsorb nitrobenzene molecules, and CB
      increases the adsorption sites. The nitrobenzene adsorption onto MAS follows
      Langmuir isotherm, implying the adsorption occurrence tends to be on a
      homogeneous surface by monolayer adsorption other than multi-layer adsorption
      which accounts for the adsorption onto UMAS. The maximum adsorption capacity of
      MAS is 40.6, 25.0 and 25.6 mg/g at 6.0, 25.0 and 40.0 degrees C, respectively.
      MAS presents to be a good adsorbent to remove nitrobenzene from water, and CB is
      a successful modifier.

PMID- 20685040
TI  - Biodegradation of phenol at high concentration by a novel fungal strain
      Paecilomyces variotii JH6.
AB  - A novel phenol-degrading filamentous fungus, strain JH6, was isolated from
      activated sludge and identified as a member of Paecilomyces variotii based on
      standard morphological and phylogenetic analysis. The degradation assays
      suggested that the strain was able to utilize phenol as the sole source of carbon
      and energy at concentrations up to 1800 mg/l. The strain exhibited optimum phenol
      degradation performance with the addition of 100 mg/l glucose at pH 5, 37 degrees
      C. Haldane's model could be fitted to the growth kinetics data well over a wide
      range of initial phenol concentrations (100-1800 mg/l), with kinetic values
      MU(max)=0.312 h(-1), K(s)=130.4 mg/l, and K(i)=200 mg/l. The decay coefficient
      was found to be 0.0073 h(-1). Complete phenol degradation by strain JH6 could be
      achieved in the presence of other toxicants, such as m-cresol and quinoline,
      which were often found in the real phenol-containing wastewater.

PMID- 20685041
TI  - Using of multi-walled carbon nanotubes electrode for adsorptive stripping
      voltammetric determination of ultratrace levels of RDX explosive in the
      environmental samples.
AB  - A study of the electrochemical behavior and determination of RDX, a high
      explosive, is described on a multi-walled carbon nanotubes (MWCNTs) modified
      glassy carbon electrode (GCE) using adsorptive stripping voltammetry and
      electrochemical impedance spectroscopy (EIS) techniques. The results indicated
      that MWCNTs electrode remarkably enhances the sensitivity of the voltammetric
      method and provides measurements of this explosive down to the sub-mg/l level in
      a wide pH range. The operational parameters were optimized and a sensitive,
      simple and time-saving cyclic voltammetric procedure was developed for the
      analysis of RDX in ground and tap water samples. Under optimized conditions, the
      reduction peak have two linear dynamic ranges of 0.6-20.0 and 8.0-200.0 mM with a
      detection limit of 25.0 nM and a precision of <4% (RSD for 8 analysis).

PMID- 20685042
TI  - Use of molecular markers for predicting therapy response in cancer patients.
AB  - Predictive markers are factors that are associated with upfront response or
      resistance to a particular therapy. Predictive markers are important in oncology
      as tumors of the same tissue of origin vary widely in their response to most
      available systemic therapies. Currently recommended oncological predictive
      markers include both estrogen and progesterone receptors for identifying patients
      with breast cancers likely to benefit from hormone therapy, HER-2 for the
      identification of breast cancer patients likely to benefit from trastuzumab,
      specific K-RAS mutations for the identification of patients with advanced
      colorectal cancer unlikely to benefit from either cetuximab or panitumumab and
      specific EGFR mutations for selecting patients with advanced non-small-cell lung
      cancer for treatment with tyrosine kinase inhibitors such as gefitinib and
      erlotinib. The availability of predictive markers should increase drug efficacy
      and decrease toxicity, thus leading to a more personalized approach to cancer
      treatment.

PMID- 20685043
TI  - Cortisol rapidly disrupts prepulse inhibition in healthy men.
AB  - Stress is known to affect sensorimotor gating (measured with prepulse inhibition
      of startle, or PPI), possibly improving perception of threat signals at the
      expense of other input during states of arousal. Stress also induces a variety of
      autonomic nervous system and endocrine responses, such as an activation of the
      hypothalamic-pituitary-adrenal axis. The latter will result in the release of the
      stress hormone cortisol which is known to exert rapid and sustained action on
      several CNS processes. Since previous studies have not clarified whether and
      which stress response components may mediate effects on sensorimotor gating, this
      study asked whether a link may exist between cortisol and sensorimotor gating. We
      tested whether cortisol may affect PPI by assessing PPI before, during, and after
      non-stressful, covert 1mg IV cortisol infusions in 27 healthy men in a single
      blind and placebo-controlled within-subject design. Cortisol induced a rapid
      reduction of PPI, with its maximum at 20 min after administration, and PPI
      returned to baseline after another 20 min. Startle magnitude in the absence of a
      prepulse was not affected. This rapid effect of the IV cortisol infusions is
      probably mediated by a non-genomic mechanism. We conclude that stress effects on
      sensorimotor gating may be mediated by glucocorticoids. The disruption of
      sensorimotor gating by the stress hormone cortisol may serve the processing of
      intense and potentially dangerous startling stimuli.

PMID- 20685044
TI  - Event-level associations between affect, alcohol intoxication, and acute
      dependence symptoms: Effects of urgency, self-control, and drinking experience.
AB  - This study used experience sampling to examine within-person associations between
      positive affect, anxiety, sadness, and hostility and two outcomes: alcohol
      intoxication and acute dependence symptoms. We examined the role of urgency,
      premeditation, and perseverance in predicting the alcohol outcomes and tested
      whether the affective associations varied as a function of urgency. Participants
      completed baseline assessments and 21 days of experience sampling on PDAs.
      Hypotheses were partially confirmed. Positive affect was positively, and sadness
      inversely, associated with intoxication. Hostility was associated with
      intoxication for men but not women. Negative urgency moderated the association
      between anxiety and intoxication, making it stronger. However, positive urgency
      did not moderate the effect of positive affect. Heavier drinkers exhibited the
      greatest number of symptoms, yet the association between intoxication and acute
      signs of alcohol disorder was attenuated among these individuals. Results support
      the use of experience sampling to study acute signs and symptoms of high risk
      drinking and dependence.

PMID- 20685045
TI  - Authentication of meat and meat products.
AB  - In recent years, interest in meat authenticity has increased. Many consumers are
      concerned about the meat they eat and accurate labelling is important to inform
      consumer choice. Authentication methods can be categorised into the areas where
      fraud is most likely to occur: meat origin, meat substitution, meat processing
      treatment and non-meat ingredient addition. Within each area the possibilities
      for fraud can be subcategorised as follows: meat origin-sex, meat cuts, breed,
      feed intake, slaughter age, wild versus farmed meat, organic versus conventional
      meat, and geographic origin; meat substitution-meat species, fat, and protein;
      meat processing treatment-irradiation, fresh versus thawed meat and meat
      preparation; non-meat ingredient addition-additives and water. Analytical methods
      used in authentication are as diverse as the authentication problems, and include
      a diverse range of equipment and techniques. This review is intended to provide
      an overview of the possible analytical methods available for meat and meat
      products authentication. In areas where no authentication methods have been
      published, possible strategies are suggested.

PMID- 20685046
TI  - Antimicrobial resistance and molecular analysis of non-typhoidal Salmonella
      isolates from human in Tunisia.
AB  - During the period from 2006 to 2007, a total of 32 clinical isolates of
      Salmonella enterica were isolated from diarrheagenic stool samples and further
      examined for their susceptibility to various antibiotics. Sixteen of the human
      isolates were from the capital Tunis, 11 were from Sousse, four were from Nabeul
      and one was from Mahdia, Tunisia. The isolates were serotyped and identified at
      the National Centre of Enteropathogenic Bacteria, Pasteur Institute, Tunis
      (Centre National de Salmonella, Shigella et Vibrio - Institut pasteur de Tunis);
      nine distinct serovars were identified: Enteritidis (n=20), Typhimurium (n=4),
      Zanzibar (n=2), Manhattan (n=1), Bovismorbificans (n=1), Amsterdam (n=1), Saint
      Paul (n=1), Kentucky (n=1) and Muenster (n=1). Our results showed that 25
      Salmonella isolates (78.1 %) were resistant to antibiotics with 20 isolates (62.5
      %) displayed resistance to ampicillin. Isolates sharing invA gene, as shown by
      PCR amplification, were further characterized by the techniques of pulsed-field
      gel electrophoresis (PFGE) using the restriction enzyme XbaI and plasmid analysis
      to determine possible genetic relationships among Salmonella enterica clinical
      isolates and to assess genetic diversity. Plasmid profiling identified seven
      plasmid profiles (with 1-5 plasmids) among the isolates; four isolates
      (Salmonella Kentucky, Salmonella Muenster, Salmonella Bovismorbificans and
      Salmonella Zanzibar) did not carry any plasmid. The isolates were differentiated
      into 10 distinct XbaI-pulsotypes. Our findings show genetic diversity among the
      different serovars and cluster analysis of compiled serotyping, PFGE, plasmid
      profiling and antibiotic resistance data provided additional discrimination.

PMID- 20685047
TI  - Genotypic evolution and antigenic drift of H9N2 influenza viruses in China from
      1994 to 2008.
AB  - H9N2 influenza viruses have been circulating in China since 1994, but a
      systematic investigation of H9N2 in northern China has not been undertaken since
      2004. Here, using the sequences of 22 viruses we isolated from poultry and pigs
      in northern China during 2003-2008, in combination with sequences available in a
      public database, we analyzed the evolution of H9N2 influenza viruses in China
      from 1994 to 2008. Our findings demonstrated that the H9N2 viruses in China
      underwent extensive reassortment, and novel genotypes continued to emerge. Among
      330 viruses, 54 genotypes were observed including 19 novel genotypes that have
      not been recognized before, and major genotypes were further divided into five
      series (BJ/94-, G1-, BG-, F/98- and Aq-series). Different epidemiological and
      biological features among these series were recognized. The BJ/94- and F/98
      series viruses were circulating in both southern and northern China, while the
      other three series viruses were mainly detected in southern China. BJ/94-series
      influenza viruses predominated in China before 2000 and were gradually replaced
      by F/98-series viruses that became the predominant viruses since 2004. At least
      five antigenic groups could be identified over the study period, during which a
      significant antigenic drift likely occurred between 2002 and 2003. Animal
      experiments demonstrated that F/98-series viruses were able to replicate and
      transmit more effectively in chickens than BJ/94-series viruses. The continuing
      evolution of H9N2 influenza viruses in China emphasizes the importance of H9N2
      influenza virus surveillance throughout this region to aid pandemic prediction
      and prevention.

PMID- 20685048
TI  - An assessment of the efficiency of PrPsc detection in rectal mucosa and third
      eyelid biopsies from animals infected with scrapie.
AB  - In classical scrapie, detection of PrPsc on lymphoreticular system is used for
      the in vivo and post mortem diagnosis of the disease. However, the sensitivity of
      this methodology is not well characterised because the magnitude and duration of
      lymphoid tissue involvement can vary considerably. The aim of the present study
      was to evaluate the efficiency of detecting PrPsc in rectal mucosa and third
      eyelid biopsies. A total of 474 genetically susceptible sheep and 24 goats from
      three scrapie infected flocks were included in this study. A sample from rectal
      mucosa and a sample from third-eyelid lymphoid tissue were collected from each
      animal. Biopsy samples were fixed in formaldehyde and processed for
      immunohistochemical examination. Animals with negative biopsy results were
      studied more closely through a post mortem examination of central nervous and
      lymphoreticular systems and if there was a positive result, additional biopsy
      sections were further tested. The sensitivity of rectal mucosa and third-eyelid
      assays were 36% and 40% respectively on initial examination but increased to 48%
      and 44% respectively after retesting. The results of this field study show a high
      percentage of infected animals that do not have detectable levels of PrPsc in the
      biopsied lymphoid tissue, due mainly to the relatively high number of animals
      with minimal or no involvement of lymphoid tissue in the pathogenesis of the
      disease.

PMID- 20685049
TI  - Differential expression of estrogen receptor alpha gene in the ampullae and
      isthmus regions of the rabbit oviduct during early pregnancy.
AB  - We characterized the expression pattern of estrogen receptor alpha (ERalpha) gene
      in two regions of the oviduct, ampullae and isthmus, of the rabbit (Oryctolagus
      cuniculus) during early pregnancy (1-4 days) by RT-PCR and immunohistochemistry.
      In both regions of the oviduct, ERalpha mRNA was increased (P<0.01) in pregnant
      rabbits as compared with non-pregnant animals (NG). In the ampullae, the greatest
      amount of ERalpha mRNA was detected on the third day of pregnancy (1.01+/-0.02
      relative amount), followed by a decrease on Day 4. In the isthmus, an increase in
      ERalpha mRNA was observed during the first 4 days of pregnancy, with the greatest
      amount on Day 3 (1.49+/-0.3 relative amount). A marked ERalpha immunostaining was
      detected in epithelial, stromal and smooth muscle cells of the ampullae on the
      second and third days of pregnancy as compared with the NG group. In contrast, a
      significant increase in ERalpha immunostaining was observed on the first and
      second days of pregnancy with a reduction on the third and fourth days in the
      epithelial, stromal and smooth muscle cells of the isthmus. The overall results
      suggest there is differential expression pattern for the ERalpha gene in the
      ampullae and isthmus during early pregnancy of the rabbit, and that these
      variations are related to specific functions of ERalpha in the reproductive tract
      during early pregnancy.

PMID- 20685050
TI  - The detection of mephedrone (4-methylmethcathinone) in 4 fatalities in Scotland.

PMID- 20685051
TI  - Detection of long-term progression of myocardial fibrosis in Duchenne muscular
      dystrophy in an affected family: a cardiovascular magnetic resonance study.
AB  - BACKGROUND: Detection of myocardial fibrosis and left ventricular dysfunction in
      Duchenne muscular dystrophy (DMD) is the corner stone for further therapeutic
      studies. Little is known about the ability of cardiac magnetic resonance imaging
      (CMR) to evaluate progression of myocardial fibrosis. Aim of our study was to
      provide CMR data in a previously genotyped DMD family and to evaluate whether
      progression of myocardial fibrosis could be visualized. METHODS AND RESULTS: DMD
      genotypes were available in 14 family members. CMR was performed in 4/5 carrier
      females, in 2/2 affected males and in one healthy family member with normal
      genotype. Functional images and late gadolinium enhanced (LGE) images in
      contiguous short-axis orientation were acquired at baseline and follow-up of 1231
      days CMR examination could be repeated in three carrier females, in one affected
      male and in the healthy subject previously scanned. Mean decrease of left
      ventricular ejection fraction during the follow-up period was 10.5+/-11.0%, mean
      progression of LGE volume 11.7+/-9.5%. CONCLUSIONS: Myocardial fibrosis seems to
      occur prior to global left ventricular dysfunction in DMD diseased males and
      carrier females. CMR could be used to evaluate progression of myocardial fibrosis
      and left ventricular function and may thus serve as an important diagnostic tool
      in the evaluation of therapeutical options in DMD.

PMID- 20685052
TI  - Interrelationships between 3-T-MRI-derived cortical and trabecular bone structure
      parameters and quantitative-computed-tomography-derivedbone mineral density.
AB  - Recently, 3-T magnetic resonance imaging (MRI) has been introduced for bone
      imaging. Through higher signal-to-noise ratios, as compared to 1.5-T MRI, it
      promises to be a more powerful tool for the assessment of cortical and trabecular
      bone measures. The goal of our study was to compare MRI-derived cortical and
      trabecular bone measures to quantitative computed tomography (QCT)-derived bone
      mineral density (BMD). Using 3-T MRI in 51 postmenopausal women, apparent (app.)
      measures of bone volume/total volume, trabecular number (Tb.N), trabecular
      thickness (Tb.Th) and trabecular separation were derived at the distal radius,
      distal tibia and calcaneus. Cortical thickness (Ct.Th) was calculated at the
      distal radius and distal tibia. These measures were compared to QCT-derived BMD
      of the spine, hip and radius. Significant correlations ((*)P<.05; (**)P<.001;
      (***)P<.0001) were found between spine BMD- and MRI-derived Ct.Th (r(radius)=.55,
      (*)P<.05; r(tibia)=.67, (***)P<.0001) and app. Tb.N (r(radius)=.33, (*)P<.05;
      r(tibia)=.35, (*)P<.05) at the radius and tibia. Furthermore, within the first 10
      mm at the radius, an inverse correlation for Ct.Th and app. BV/TV (r(6mm)=-.56,
      P<.001; r(10mm)=-.36, P<.05) and app. Tb.Th (r(6mm)=-.54, P<.001; r(10mm)=-.41,
      P<.05) was found.

PMID- 20685053
TI  - Measurement of relative cerebral blood volume using BOLD contrast and mild
      hypoxic hypoxia.
AB  - Relative cerebral blood volume (CBV) was estimated using a mild hypoxic challenge
      in humans, combined with BOLD contrast gradient-echo imaging at 3 T. Subjects
      breathed 16% inspired oxygen, eliciting mild arterial desaturation. The
      fractional BOLD signal change induced by mild hypoxia is expected to be
      proportional to CBV under conditions in which there are negligible changes in
      cerebral perfusion. By comparing the regional BOLD signal changes arising with
      the transition between normoxia and mild hypoxia, we calculated CBV ratios of 1.5
      +/- 0.2 (mean +/- S.D.) for cortical gray matter to white matter and 1.0 +/- 0.3
      for cortical gray matter to deep gray matter.

PMID- 20685054
TI  - Identification of efferent flow in the superior vena cava and azygos vein
      confluence using cine phase-contrast MRI: speculation of the role of the azygos
      arch valves.
AB  - PURPOSE: We aimed to evaluate flow patterns in the superior vena cava (SVC) and
      azygos vein confluence with cine phase-contrast magnetic resonance imaging with
      consideration for the role played by the azygos arch valves. MATERIALS AND
      METHODS: Two-dimensional cine phase-contrast magnetic resonance images of the SVC
      and azygos vein confluence were prospectively acquired in 10 healthy volunteers.
      Flow directions during the cardiac cycle were evaluated quantitatively using
      sequential flow profile graphs obtained from each orthogonal image and affirmed
      visually by two radiologists from the oblique sagittal cine images. RESULTS:
      Although the blood in the SVC and azygos vein confluence had an afferent flow
      during the systolic phase, a slight temporal efferent flow during the diastolic
      phase was quantitatively observed in all cases. Flow in the SVC can also be
      confirmed visually. The average velocity, average maximum afferent velocity
      during the systolic phase and average maximum efferent velocity during the
      diastolic phase of the SVC were 8.7 +/- 2.4, 19.9 +/- 3.7 and -1.0 +/- 3.2 cm/s,
      respectively; for the azygos vein confluence, these values were 2.2 +/- 1.5, 7.1
      +/- 2.6 and -1.5 +/- 1.1 cm/s, respectively. CONCLUSION: We verified that a
      slight temporal efferent flow exists in the SVC and azygos vein confluence during
      the diastolic phase, which suggests that the usual role of the azygos arch valves
      is to prevent this physiological retrograde flow.

PMID- 20685055
TI  - Ultrasound-guided distal popliteal sciatic nerve block for ED anesthesia.

PMID- 20685057
TI  - Hypokalemia and muscle paralysis after low-dose methylprednisolone.

PMID- 20685056
TI  - Out-of-hospital emergency medicine in pediatric patients: prevalence and
      management of pain.
AB  - INTRODUCTION: Much less is known about pain prevalence in pediatric patients in
      an out-of-hospital than emergency department setting. The purpose of this study
      was to determine pain prevalence in children in a prehospital emergency setting
      and to identify the factors associated with pain relief. MATERIALS AND METHODS:
      This prospective cohort study in consecutive patients 15 years or younger was
      conducted by 5 mobile intensive care units working 24/7 (January-December 2005).
      The presence of pain, its intensity, and alleviation by the administration of
      analgesics were recorded. RESULTS: A total of 258 of 433 pediatric patients were
      included, of whom 96 were suffering from acute pain (37%; 95% confidence interval
      [CI], 31-43) that was intense to severe in 67% of cases. Trauma was the only
      factor significantly associated with acute pain (odds ratio, 818; 95% CI, 153
      4376). Overall, 92% of the children in pain received at least one analgesic drug;
      41% received a combination of drugs. Opioid administration was significantly
      associated with intense to severe pain (odds ratio, 7; 95% CI, 2-25). On arrival
      at hospital, 67% of the children were still in pain; but 84% had experienced some
      pain relief regardless of their sex, age, or disorder. CONCLUSION: In a
      prehospital emergency setting, more than a third of children experience acute
      pain with a high prevalence of intense to severe pain. Scoring pain in children,
      and especially in the newborn, is beleaguered by a lack of suitable scales.
      Despite this, it was possible to treat 90% of children in pain and provide relief
      in 80% of cases.

PMID- 20685058
TI  - Thrombolysis by recombinant tissue plasminogen activator during pregnancy: a case
      of massive pulmonary embolism.

PMID- 20685059
TI  - Neurologically intact survival despite severe sepsis-induced hypogylcemia: a case
      report.

PMID- 20685060
TI  - Acute urinary retention as the initial manifestation of Guillain-Barre syndrome.

PMID- 20685061
TI  - Hypertension in the ED: a multifaceted intervention to change provider practice.
AB  - This project measured the effect of a multifaceted intervention on health care
      provider identification and treatment of undiagnosed hypertensive patients. The
      intervention comprised provider education, audit, and feedback. The primary
      outcomes were pre-/postintervention differences in the proportion of patients
      presenting with elevated blood pressure who were (1) identified, (2) given blood
      pressure measurements, (3) counseled regarding behavior change, (4) prescribed
      medications, and (5) advised of the need for follow-up. These 5 behaviors were
      selected based on the recommendations in the seventh report of the Joint National
      Committee on Prevention, Detection, Evaluation, and Treatment of High Blood
      Pressure. Rates of all 5 outcomes improved significantly after the intervention,
      with prevalence differences ranging from 5% to 25%. However, despite increases,
      rates for each behavior remained low. At no point during the study were all 5
      practitioner behaviors documented for an individual patient. In conclusion, while
      an intervention composed of education and practitioner audit and feedback
      improved practitioner behaviors in treating patients with elevated blood
      pressure, additional interventions are needed to bring practitioner behaviors up
      to the level of JACHO standards.

PMID- 20685062
TI  - Severe chest pain during stress dobutamine echocardiogram in patient with patent
      epicardial coronary arteries.
AB  - Dobutamine induced ST-segment elevation in the absence of obstructive coronary
      artery disease is a rare condition. We report a case of a 37-year-old man, a
      smoker, who developed severe chest pain associated with transient ST-segment
      elevation in anterolateral leads and significant segmental wall motion
      abnormalities during dobutamine stress echocardiography that was immediately
      relieved by sublingual nitrates without evidence of acute myocardial infarction.
      Coronary angiogram showed patent epicardial coronary arteries.

PMID- 20685063
TI  - Evaluation of intramuscular fosphenytoin vs intravenous phenytoin loading in the
      ED.
AB  - OBJECTIVE: A comparison of length of stay in an emergency department (ED) after
      loading patients at risk for seizures with either intravenous (IV) phenytoin or
      intramuscular (IM) fosphenytoin was studied. METHODS: This was a retrospective
      observational cohort study that was conducted over a 24-month period in an
      academic teaching hospital (693 beds). Patients included were 18 years or older,
      discharged from the ED without hospital admission, and loaded with either IV
      phenytoin or IM fosphenytoin. The primary end point was the comparison of length
      of stay in the ED until discharge after loading. Characterization of seizure
      etiology, cardiac risk factors, and adverse drug events were also observed.
      RESULTS: A total of 51 patients were evaluated who received IV phenytoin compared
      with 59 for IM fosphenytoin. The median time-to-discharge difference between IV
      phenytoin vs IM fosphenytoin was 1:49 hours (95% confidence interval, 1:24-2:24
      hours; P < .001). There was no statistical difference in cardiac risk factors and
      occurrence of adverse drug events between groups. CONCLUSIONS: This study found
      that patients were discharged from the ED earlier with the loading of IM
      fosphenytoin compared to IV phenytoin.

PMID- 20685064
TI  - A pilot study to develop a prediction instrument for endocarditis in injection
      drug users admitted with fever.
AB  - OBJECTIVE: Seeking to evaluate the feasibility of a prediction instrument for
      endocarditis in febrile injection drug users (IDUs), we determined (1) the
      frequency percentage of IDUs admitted with fever diagnosed with endocarditis and
      (2) whether individual or combinations of emergency department (ED) clinical
      criteria (patient history, physical examination findings, and laboratory tests)
      are associated with endocarditis in IDUs admitted to rule out endocarditis.
      METHODS: The ED and inpatient charts of all IDUs with a diagnosis of rule out
      endocarditis admitted at 3 urban hospitals in 2006 were reviewed. Screening
      performance of individual criteria was determined, and the most sensitive
      combination of criteria was derived by classification tree analysis. RESULTS: Of
      236 IDUs admitted with fever, 20 (8.5%) were diagnosed with endocarditis. Lack of
      skin infection, tachycardia, hyponatremia, pneumonia on chest radiograph, history
      of endocarditis, thrombocytopenia, and heart murmur had the best screening
      performance. The classification tree-derived best criteria combination of
      tachycardia, lack of skin infection, and cardiac murmur had a sensitivity of 100%
      (95% confidence interval, 84%-100%) and negative predictive value of 100% (95%
      confidence interval, 88%-100%). CONCLUSIONS: Using ED clinical criteria, a
      multicenter prospective study to develop an instrument for endocarditis
      prediction in febrile IDUs is feasible, with an estimated target enrollment of
      588 patients.

PMID- 20685065
TI  - Vasculitis presenting with myocardial infarction, stroke, and aortitis in a
      middle-aged man.
AB  - BACKGROUND: Vasculitis may cause inflammation in any single or group of blood
      vessels. Traditionally, giant cell arteritis involves the extracranial branches
      of the carotid, and Takayasu arteritis affects the aorta and its major branches.
      These diseases are quite rare, but have the potential to be fatal. OBJECTIVES: We
      describe the spectrum of overlap between these two historically distinct
      diseases, and use a case of a man with arteritis involving his carotid and
      vertebral vessels, aorta, and coronary arteries to illustrate this. We posit that
      large-vessel vasculitis should be considered in the differential for young and
      middle-aged patients presenting with multiple vascular events. CASE REPORT: Over
      a 2-month period, a 46-year-old man presented on four separate occasions to the
      Emergency Department. Each time, he was diagnosed with a vascular event. His
      first two visits were for myocardial infarction and unstable angina, his third
      visit was for a cerebrovascular event, and his fourth visit was for aortitis. He
      was not diagnosed with the underlying vasculitic process until his last visit. He
      ultimately succumbed to non-aneurysmal aortic rupture from his aortitis.
      CONCLUSIONS: In middle-aged persons with multiple vascular events, an underlying
      inflammatory process should be considered. These diseases are rare, but they are
      treatable; and missed diagnoses can be catastrophic.

PMID- 20685066
TI  - Interrater reliability for the Four Habits Coding Scheme as part of a randomized
      controlled trial.
AB  - OBJECTIVE: To describe the process for developing interrater reliability (IRR)
      for the Four Habits Coding Scheme (4HCS) for a heterogeneous material as part of
      a randomized controlled trial. METHODS: Videotapes from 497 hospital encounters
      involving 71 doctors from most clinical specialties were collected. Four
      experienced psychology students were trained as raters. We calculated Pearson's r
      and the intraclass correlation (ICC) on the total score across consecutive
      samples of twenty videos, and Pearson's r on single videos across items in the
      initial coding phase. RESULTS: After 18h of training and one rating session, the
      total score Pearson's r and ICC exceeded .70 for all pairs of raters. Across
      items within single videos, the Pearson's r was never below 0.60 after the first
      50 videos. At item and habit level Pearson's r remained unsatisfactory for some
      rater pairs mostly due to low variance on some items. CONCLUSION: Based on the
      evaluation of the effect of communication skills training via a total score, IRR
      was satisfactory for the 4HCS as applied to heterogeneous material. However, good
      reliability at item level was difficult to achieve. PRACTICE IMPLICATIONS: 4HCS
      may be used as an outcome measure for clinical communication skills in randomized
      controlled trials.

PMID- 20685067
TI  - Technicalities: Getting and staying connected to people living with HIV/AIDS in
      the southern United States.

PMID- 20685068
TI  - Language barriers and patient-centered breast cancer care.
AB  - OBJECTIVE: Provision of high quality patient-centered care is fundamental to
      eliminating healthcare disparities in breast cancer. We investigated physicians'
      experiences communicating with limited English proficient (LEP) breast cancer
      patients. METHODS: Survey of a random sample of California oncologists and
      surgeons. RESULTS: Of 301 respondents who reported treating LEP patients, 46%
      were oncologists, 75% male, 68% in private practice, and on average 33% of their
      patients had breast cancer. Only 40% reported at least sometimes using
      professional interpretation services. Although 75% felt they were usually able to
      communicate effectively with LEP patients, more than half reported difficulty
      discussing treatment options and prognosis, and 56% acknowledged having less
      patient-centered treatment discussions with LEP breast cancer patients. In
      multivariate analysis, use of professional interpreters was associated with 53%
      lower odds of reporting less-patient-centered treatment discussions (OR 0.47; 95%
      CI 0.26-0.85). CONCLUSION: California surgeons and oncologists caring for breast
      cancer patients report substantial communication challenges when faced with a
      language barrier. Although use of professional interpreters is associated with
      more patient-centered communication, there is a low rate of professional
      interpreter utilization. PRACTICE IMPLICATIONS: Future research and policy should
      focus on increasing access to and reimbursement for professional interpreter
      services.

PMID- 20685069
TI  - Mechanisms of tumor growth retardation by modulation of pH regulation in the
      tumor-microenvironment of a murine T cell lymphoma.
AB  - Mechanisms underlying tumor growth retarding effect of proton pump inhibitor
      pantoprazole (PPZ) on a murine T cell lymphoma, designated as Dalton's lymphoma
      (DL), were investigated. In vivo administration of PPZ to tumor-bearing mice
      resulted in retardation of tumor progression owing to an inhibition of tumor cell
      survival and augmented apoptosis. An alteration in the parameters of tumor
      microenvironment and modulation in the expression of cell growth regulatory
      molecules is indicated to be involved in PPZ-dependent tumor growth retardation.
      These findings will help in optimizing therapeutic strategies against cancer
      using PPZ.

PMID- 20685070
TI  - Erythropoietin prevents reactive oxygen species generation and renal tubular cell
      apoptosis at high glucose level.
AB  - Erythropoietin (EPO) can induce a series of cytoprotective effects in many non
      hematopoietic tissues through interaction with the erythropoietin receptor
      (EPOR), but whether EPO can prevent the overproduction of reactive oxygen species
      (ROS) and apoptosis in diabetes remains unclear. Here, we report that renal
      tubular cells possess EPOR and that EPO reduces high glucose-induced oxidative
      stress in renal tubular cells. Further, we found that EPO inhibited high glucose
      induced renal tubular cell apoptosis and that this protective effect was
      dependent on reduction of Bax/caspase-3 expression as well as elevation of Bcl-2
      expression. Our results suggest that EPO can inhibit high glucose-induced renal
      tubular cell apoptosis through direct effect on anti-oxidative stress and that
      EPOR may play a key role in this process.

PMID- 20685071
TI  - Provision of pain- and symptom-relieving drugs for HIV/AIDS in sub-Saharan
      Africa.
AB  - CONTEXT: Although pain and burdensome symptoms among HIV-infected persons can be
      effectively managed, the availability of opioids and other symptom-controlling
      drugs is a particular challenge in sub-Saharan Africa. OBJECTIVES: This study
      aimed to identify current drug availability and prescribing practices in 12 sub
      Saharan African countries and to examine the barriers and potential facilitators
      for use of opioids and other key HIV/AIDS symptom-controlling drugs. METHODS:
      This was a cross-sectional survey, integrating data from palliative care
      facilities and competent authorities within ministries of health in 12 African
      countries. RESULTS: Of 62 responding facilities, problems were reported in
      accessing named nonopioids, with a small number of facilities unable to dispense
      them. Less than half the facilities were currently prescribing opioids of any
      strength. Further problems were identified in terms of the availability and
      supply continuity of named antiemetics and anxiolytics. The data identified a
      number of systemic problems, suggesting that opioid supply issues are similar to
      less controlled drugs, such as antiemetics. Among competent authorities, there
      was no agreement on whether further opioid expansion was possible. Integration of
      data from care facilities and competent authorities highlighted a disparity in
      the understanding of the availability of specific drugs, with competent
      authorities naming drugs that were not listed by any responding facility in their
      respective country. CONCLUSION: This study shows that opioid expansion needs to
      balance supply and skills: Currently there are insufficient trained clinical
      personnel to prescribe, and supply is unreliable. Efforts to expand supply should
      ensure that they do not weaken current systems.

PMID- 20685072
TI  - Psychometric properties of the Spence Child Anxiety Scale with adolescents from
      five European countries.
AB  - This study examined the factor structure, reliability, and validity of the
      original Spence Child Anxiety Scale (SCAS) and its four translations (German,
      Cypriot Greek, Swedish, Italian). A total of 2558 adolescents from five European
      countries (Germany = 495; Cyprus = 611; UK = 469; Sweden = 484; Italy = 499),
      ages 12-17 years, participated in the study. In addition to the SCAS, all
      participants completed the Strengths and Difficulties Questionnaire, a measure of
      general difficulties and positive attributes. The internal consistency and
      validity (convergent and discriminant) of the SCAS were excellent. Multiple group
      confirmatory factor analysis provided strong support for the generalizability of
      a 6-factor inter-correlated model across five European countries. Adolescents in
      the UK had significantly higher anxiety levels than adolescents in four other
      European countries. Our findings suggest that the SCAS is suitable for assessing
      anxiety disorder symptoms in adolescents in Germany, the UK, Cyprus, Sweden, and
      in Italy.

PMID- 20685073
TI  - Massive aneurysm in a persistent sciatic artery.
AB  - Persistent sciatic artery (PSA) is an exceptionally rare embryological vascular
      anomaly with a reported incidence, based on angiographic series, of between 0.01
      and 0.05%. We report a case of a patient with bilateral PSAs and a unilateral 12
      cm aneurysm arising from the left PSA. As with our case, most PSAs are among the
      dominant arteries that supply blood to the lower limb with aneurysm formation
      occurring in up to 40% of cases. The femoral artery is often hypoplastic.
      Presentation usually includes symptoms and signs of an enlarged buttock mass,
      sciatic nerve compression, and distal limb ischemia. An interposition inlay graft
      is the preferred method of surgical repair. Dissection of the aneurysm is not
      recommended because of risk of damage to the sciatic artery. Endovascular stent
      placement is an accepted method of repair but does not deal with any local
      symptoms of the expanding aneurysm.

PMID- 20685074
TI  - Energy expended by adults with and without intellectual disabilities during
      activities of daily living.
AB  - The aims of this study were to (1) determine the energy expenditure of adults
      with and without intellectual disabilities during common activities of daily
      living (ADL), (2) use these values to evaluate the accuracy of equivalent
      activity values reported in the Compendium of Physical Activities (CPA), and (3)
      identify ADL that may confer a health benefit for adults with intellectual
      disabilities when undertaken regularly. Energy expenditure was measured for
      adults with intellectual disabilities (N=31; 29.0+/-8.6 yr) and adults without
      intellectual disabilities (N=15; 30.4+/-9.6 yr) while undertaking each of seven
      ADL: sitting quietly (SitQ); sitting watching television (SitTV); sitting and
      standing while completing an assembly task (SitAT, StaAT); and walking at a slow
      (WalkS, 3.0 km h(-1)), quick (WalkQ, 6.0 km h(-1)) and fast (WalkF, 9.0 km h(-1))
      speed, under laboratory conditions. Adults with intellectual disabilities were
      found to expend significantly more energy than adults without intellectual
      disabilities for SitQ, WalkS, WalkQ and WalkF (p<0.05). Energy expended by both
      populations was significantly more than CPA values for SitQ, SitTV, SitAT, WalkS,
      and WalkQ (p<0.02) and significantly less for WalkF (p<0.01). Walking at the
      speed of 3.0 km h(-1) (50 m min(-1)) was found to be sufficient to achieve
      moderate-intensity energy expenditure, surpassing the intensity threshold for
      conferring a health benefit. Energy expenditure inaccuracies of the CPA have
      important consequences when estimating prevalence of engagement in health
      enhancing physical activities among population sub-groups. The identification of
      slow walking as a moderate-intensity physical activity offers significant health
      promotion opportunities for adults with intellectual disabilities through active
      transport and leisure.

PMID- 20685075
TI  - Cytochrome c oxidase deficiency in human posterior cricoarytenoid muscle.
AB  - BACKGROUND: Mitochondrial alterations occur in skeletal muscle fibers throughout
      the normal aging process, resulting from increased accumulation of reactive oxide
      species (ROS). These result in respiratory chain abnormalities, which decrease
      the oxidative capacity of muscle fibers, leading to decreased contractile force,
      sarcopenia, or fiber necrosis. Intrinsic laryngeal muscles are a cranial muscle
      group that possesses some distinctive genotypic, phenotypic, and physiologic
      properties. Their susceptibility to mitochondrial alterations resulting from
      biological processes that increase levels of oxidative stress may be one of these
      distinctive characteristics. OBJECTIVES: The incidence of cytochrome c oxidase
      (COX) deficiency (COX(-)) was determined in human posterior cricoarytenoid (PCA)
      muscle when compared with the human thyrohyoid (TH) muscle, an extrinsic
      laryngeal muscle that served as "control" muscle. Ten PCA and 10 TH muscles were
      harvested postlaryngectomy from 10 subjects ranging in age from 55 to 86 years.
      Differences in COX(-) were compared within and between muscle types using tissue
      section staining and standard morphometric analysis. RESULTS AND CONCLUSIONS:
      COX(-) fibers were identified in both the PCA and TH muscles. The PCA muscle had
      10 times as may affected fibers as the TH muscle, with significant differences in
      COX(-) found between muscle type and fiber type (P=0.003). Almost all of this
      effect was the result of elevated levels of COX(-) in type I fibers from the PCA
      muscle (P=0.002) that showed a strong positive correlation with increased age.
      These results suggest that increased mitochondrial alterations may occur in the
      PCA muscle during normal aging.

PMID- 20685076
TI  - Hierarchical classification of dynamically varying radar pulse repetition
      interval modulation patterns.
AB  - The central purpose of passive signal intercept receivers is to perform automatic
      categorization of unknown radar signals. Currently, there is an urgent need to
      develop intelligent classification algorithms for these devices due to emerging
      complexity of radar waveforms. Especially multifunction radars (MFRs) capable of
      performing several simultaneous tasks by utilizing complex, dynamically varying
      scheduled waveforms are a major challenge for automatic pattern classification
      systems. To assist recognition of complex radar emissions in modern intercept
      receivers, we have developed a novel method to recognize dynamically varying
      pulse repetition interval (PRI) modulation patterns emitted by MFRs. We use
      robust feature extraction and classifier design techniques to assist recognition
      in unpredictable real-world signal environments. We classify received pulse
      trains hierarchically which allows unambiguous detection of the subpatterns using
      a sliding window. Accuracy, robustness and reliability of the technique are
      demonstrated with extensive simulations using both static and dynamically varying
      PRI modulation patterns.

PMID- 20685077
TI  - Five preference-based indexes in cataract and heart failure patients were not
      equally responsive to change.
AB  - OBJECTIVE: To compare the responsiveness to clinical change of five widely used
      preference-based health-related quality-of-life indexes in two longitudinal
      cohorts. STUDY DESIGN AND SETTING: Five generic instruments were simultaneously
      administered to 376 adults undergoing cataract surgery and 160 adults in heart
      failure management programs. Patients were assessed at baseline and reevaluated
      after 1 and 6 months. The measures were the Short Form (SF)-6D (based on
      responses scored from SF-36v2), Self-Administered Quality of Well-being Scale
      (QWB-SA), the EuroQol-5D developed by the EuroQol Group, the Health Utilities
      Indexes Mark 2 (HUI2) and Mark 3 (HUI3). Cataract patients completed the National
      Eye Institute Visual Functioning Questionnaire-25, and heart failure patients
      completed the Minnesota Living with Heart Failure Questionnaire. Responsiveness
      was estimated by the standardized response mean. RESULTS: For cataract patients,
      mean changes between baseline and 1-month follow-up for the generic indices
      ranged from 0.00 (SF-6D) to 0.052 (HUI3) and were statistically significant for
      all indexes except the SF-6D. For heart failure patients, only the SF-6D showed
      significant change from baseline to 1 month, whereas only the QWB-SA change was
      significant between 1 and 6 months. CONCLUSIONS: Preference-based methods for
      measuring health outcomes are not equally responsive to change.

PMID- 20685078
TI  - The Patient-Reported Outcomes Measurement Information System (PROMIS) developed
      and tested its first wave of adult self-reported health outcome item banks: 2005
      2008.
AB  - OBJECTIVES: Patient-reported outcomes (PROs) are essential when evaluating many
      new treatments in health care; yet, current measures have been limited by a lack
      of precision, standardization, and comparability of scores across studies and
      diseases. The Patient-Reported Outcomes Measurement Information System (PROMIS)
      provides item banks that offer the potential for efficient (minimizes item number
      without compromising reliability), flexible (enables optional use of
      interchangeable items), and precise (has minimal error in estimate) measurement
      of commonly studied PROs. We report results from the first large-scale testing of
      PROMIS items. STUDY DESIGN AND SETTING: Fourteen item pools were tested in the
      U.S. general population and clinical groups using an online panel and clinic
      recruitment. A scale-setting subsample was created reflecting demographics
      proportional to the 2000 U.S. census. RESULTS: Using item-response theory (graded
      response model), 11 item banks were calibrated on a sample of 21,133, measuring
      components of self-reported physical, mental, and social health, along with a 10
      item Global Health Scale. Short forms from each bank were developed and compared
      with the overall bank and with other well-validated and widely accepted
      ("legacy") measures. All item banks demonstrated good reliability across most of
      the score distributions. Construct validity was supported by moderate to strong
      correlations with legacy measures. CONCLUSION: PROMIS item banks and their short
      forms provide evidence that they are reliable and precise measures of generic
      symptoms and functional reports comparable to legacy instruments. Further testing
      will continue to validate and test PROMIS items and banks in diverse clinical
      populations.

PMID- 20685079
TI  - 21-Hydroxylase epitopes are targeted by CD8 T cells in autoimmune Addison's
      disease.
AB  - In autoimmune adrenal deficiency, autoantibodies target the 21-hydroxylase (21OH)
      protein. However, it is presumed that autoreactive T cells, rather than
      antibodies, are the main effectors of adrenal gland destruction, but their
      identification is still lacking. We performed a T-cell epitope mapping study
      using 49 overlapping 20mer peptides covering the 21OH sequence in patients with
      isolated Addison's disease, Autoimmune Polyendocrine Syndrome 1 and 2. IFNgamma
      ELISPOT responses against these peptides were stronger, broader and more
      prevalent among patients than in controls, whatever the disease presentation.
      Five peptides elicited T-cell responses in patients only (68% sensitivity, 100%
      specificity). Blocking experiments identified IFNgamma-producing cells as CD8 T
      lymphocytes, with two peptides frequently recognized in HLA-B8+ patients and a
      third one targeted in HLA-B35+ subjects. In particular, the 21OH(431-450) peptide
      was highly immunodominant, as it was recognized in more than 30% of patients, all
      carrying the HLA-B8 restriction element. This 21OH(431-450) region contained an
      EPLARLEL octamer (21OH(431-438)) predicted to bind to HLA-B8 with high affinity.
      Indeed, circulating EPLARLEL-specific CD8 T cells were detected at significant
      frequencies in HLA-B8+ patients but not in controls by HLA tetramer staining.
      This report enlightens disease-specific T-cell biomarkers and epitopes targeted
      in autoimmune adrenal deficiency.

PMID- 20685080
TI  - The role of intrinsic epithelial activation in the pathogenesis of Sjogren's
      syndrome.
AB  - Sjogren's syndrome (SS) is a chronic autoimmune disorder that is characterized by
      dysfunction and destruction of the exocrine glands. Exocrinopathy is associated
      with periductal mononuclear cell infiltrates in the affected exocrine glands and
      B-cell hyperreactivity. Epithelial cells are thought to play an important
      pathogenetic role, as suggested by the occurrence of infiltrating lesions in
      various epithelial tissues (described as autoimmune epithelitis) as well as the
      increased epithelial expression of several inflammatory proteins in the
      histopathologic lesions of patients. The application of long-term cultured non
      neoplastic salivary gland epithelial cell (SGEC) lines has permitted the more
      explicit investigation of the role of these cells in the pathophysiology of SS.
      These studies have revealed the inherent capacity of SGEC to induce and promote
      chronic inflammatory reactions, as corroborated by the constitutive or inducible
      expression of various molecules implicated in innate and acquired immune
      responses. Furthermore, significantly increased constitutive expression of
      several molecules has been observed in SGEC lines derived from SS patients, as
      compared to those obtained from disease control patients. This fact strongly
      indicates the operation of intrinsic activation mechanisms in the epithelia of SS
      patients and further supports the active participation of these cells in the
      pathogenesis of the disorder.

PMID- 20685081
TI  - Salivary epithelial cells from Sjogren's syndrome patients are highly sensitive
      to anoikis induced by TLR-3 ligation.
AB  - In certain types of cells, Toll-like receptor-3 (TLR-3) ligation by viral dsRNA
      induces apoptotic death, likely engaged into the elimination of virus-infected
      cells. We have previously shown that TLR-3 ligation on cultured non-neoplastic
      salivary gland epithelial cells (SGEC) with polyI:C (a synthetic analogue of
      viral dsRNA) results in the induction of surface immunoactive molecules, however,
      the pro-apoptotic effect of such signaling has not been addressed. In this study,
      polyI:C-treated SGEC were found to suffer severe detachment from substratum and
      subsequent apoptosis, a phenomenon suggestive of anoikis or anoikia (detachment
      induced apoptosis). PolyI:C-induced anoikis in SGEC was associated with the
      upregulation of the pro-apoptotic Bmf, BimEL and Bax and the down-regulation of
      the pro-survival Bcl-2 (real-time PCR analyses). Finally, the comparative
      analysis of SGEC lines derived from primary Sjogren's syndrome (SS) patients (SS
      SGEC) and non-SS controls had revealed that SS-SGEC are particularly susceptible
      to TLR-3-induced anoikis, as it was triggered by suboptimally low concentrations
      of polyI:C. This finding correlated with significantly higher constitutive
      surface TLR-3 expression by SS-SGEC, a feature indicative of their intrinsic
      activation status. In conclusion, TLR-3 signaling pathway in the salivary
      epithelium appears to extend beyond the induction of innate immune responses and
      to involve the activation of programmed-cell death via anoikis. In the same
      context, the increased vulnerability of SS-SGEC to the injurious effect of TLR-3
      ligation is likely associated with the intrinsic activation processes that
      apparently operate in the epithelia of SS patients, and a feature of key
      pathogenetic importance for the disorder.

PMID- 20685082
TI  - Backward and forward visual masking in schizophrenia and its relation to global
      motion and global form perception.
AB  - Whilst visual backward masking deficits in schizophrenia have been reliably
      reported and may reveal magnocellular dysfunction, forward masking, which may
      rely more heavily on the parvocellular system, has been under investigated. In a
      group of 64 schizophrenia patients and 65 matched controls we undertook a visual
      masking paradigm containing both conditions, together with tests of 'global
      motion' and 'global form' perception, two 'down-stream' visual tasks reflecting
      later processing linked to magnocellular and parvocellular function respectively.
      In the patient group, a significant but small deficit on the masking task,
      equivalent across forward and backward conditions was seen. Correlations between
      the masking and motion/form tasks supported the predominant theoretical framework
      describing the neural processes involved in masking. Performance on the motion
      and form tasks was differentiated by a trend-level motion processing deficit but
      near-normal form processing. The results suggest an 'early visual' processing
      deficit in both magno- and parvocellular systems but one which is only
      transferred to 'down-stream' processing areas with predominantly magnocellular
      input.

PMID- 20685083
TI  - Suicidality in first episode psychosis is associated with insight and negative
      beliefs about psychosis.
AB  - INTRODUCTION: Suicidal behaviour is prevalent in psychotic disorders. Insight has
      been found to be associated with increased risk for suicidal behaviour, but not
      consistently. A possible explanation for this is that insight has different
      consequences for patients depending on their beliefs about psychosis. The present
      study investigated whether a relationship between insight, negative beliefs about
      psychosis and suicidality was mediated by depressive symptoms, and if negative
      beliefs about psychosis moderated the relationship between insight and
      suicidality in patients with a first episode of psychosis (FEP). METHOD: One
      hundred ninety-four FEP-patients were assessed with a clinical interview for
      diagnosis, symptoms, functioning, substance use, suicidality, insight, and
      beliefs about psychosis. RESULTS: Nearly 46% of the patients were currently
      suicidal. Depressive symptoms, having a schizophrenia spectrum disorder, insight,
      and beliefs about negative outcomes for psychosis were independently associated
      with current suicidality; contradicting a mediating effect of depressive
      symptoms. Negative beliefs about psychosis did not moderate the effect of insight
      on current suicidality. CONCLUSION: The results indicate that more depressive
      symptoms, higher insight, and negative beliefs about psychosis increase the risk
      for suicidality in FEP-patients. The findings imply that monitoring insight
      should be part of assessing the suicide risk in patients with FEP, and that
      treating depression and counteracting negative beliefs about psychosis may
      possibly reduce the risk for suicidality.

PMID- 20685084
TI  - Lack of association between extramammary Paget's disease and human papillomavirus
      infection.

PMID- 20685085
TI  - Therapeutic drug monitoring of beta-lactams in critically ill patients: proof of
      concept.
AB  - The extreme pharmacokinetic behaviour of drugs sometimes observed in critically
      ill patients poses a significant threat to the achievement of optimal antibiotic
      treatment outcomes. Scant information on beta-lactam antibiotic therapeutic drug
      monitoring (TDM) is available. The objective of this prospective study was to
      evaluate the practicality and utility of a beta-lactam TDM programme in
      critically ill patients. TDM was performed twice weekly on all eligible patients
      at a 30-bed tertiary referral critical care unit. Blood concentrations were
      determined by fast-throughput high-performance liquid chromatography (HPLC)
      assays and were available within 12h of sampling. Dose adjustment was instituted
      if the trough or steady-state blood concentration was below 4-5x the minimum
      inhibitory concentration (MIC) or above 10x MIC. A total of 236 patients were
      subject to TDM over an 11-month period. The mean+/-standard deviation age was
      53.5+/-18.3 years. Dose adjustment was required in 175 (74.2%) of the patients,
      with 119 of these patients (50.4%) requiring dose increases after the first TDM.
      For outcome of therapy, 206 (87.3%) courses resulted in a positive treatment
      outcome and there were 30 (12.7%) treatment failures observed including 14 deaths
      and 15 courses requiring escalation to broader-spectrum agents; 1 course was
      ceased due to an adverse drug reaction. Using binomial logistic regression, only
      an elevated Acute Physiology and Chronic Health Evaluation (APACHE) II score
      (P<0.01) and elevated plasma creatinine concentration (P=0.05) were found to be
      predictive of mortality. In conclusion, further research is required to determine
      definitively whether achievement of optimal beta-lactam pharmacodynamic targets
      improves clinical outcomes.

PMID- 20685086
TI  - Clonal dissemination of meticillin-resistant and vancomycin-intermediate
      Staphylococcus aureus in a Taiwanese hospital.
AB  - Meticillin-resistant and vancomycin-intermediate Staphylococcus aureus (VISA) has
      emerged worldwide. However, clonal dissemination of VISA in hospitals has rarely
      been reported. We investigated 43 isolates of meticillin-resistant VISA
      [vancomycin minimum inhibitory concentrations (MICs) of 4 microg/mL in 35
      isolates and 8 microg/mL in 8 isolates) recovered from 21 hospitalised patients.
      A glycopeptide was given prior to isolation of VISA in 14 of the patients. Five
      patients (23.8%) died despite vancomycin therapy. All isolates were inhibited by
      tigecycline at 0.5 microg/mL, linezolid at 1 microg/mL and ceftobiprole at 2
      microg/mL. Five isolates (11.6%) had reduced susceptibility to daptomycin (MICs
      of 1-2 microg/mL). In addition, 6 of the 43 VISA isolates had decreased
      susceptibility to autolysis by 0.05% Triton X-100. All 43 VISA isolates carried
      staphylococcal chromosome cassette mec (SCCmec) type III and accessory gene
      regulator (agr) group I but none carried the Panton-Valentine leukocidin gene
      (lukS-lukF). None of the enterococcal van genes were detected in the 43 VISA
      isolates. Molecular typing generated by pulsed-field gel electrophoresis revealed
      that all isolates belonged to one pulsotype, indicating clonal dissemination of
      VISA isolates in the hospital. The high rate of non-susceptibility to daptomycin
      amongst these VISA isolates is alarming and indicates the limitation of this
      agent for the treatment of infections due to VISA.

PMID- 20685087
TI  - Microsporum canis antifungal susceptibilities: concerns regarding their clinical
      predictability.

PMID- 20685088
TI  - Susceptibility of Candida albicans biofilms to azithromycin, tigecycline and
      vancomycin and the interaction between tigecycline and antifungals.
AB  - Despite growing data on antimicrobial lock therapy (ALT) in treating bacterial
      catheter-related bloodstream infections (CR-BSIs), ALT has not been established
      as a treatment option for CR-BSI caused by Candida albicans. Based on our finding
      that high-dose doxycycline exhibited antifungal activity against mature C.
      albicans biofilms, we evaluated additional antibacterial agents with Gram
      positive activity [azithromycin, tigecycline (TIG) and vancomycin]. After
      screening these antibiotics, it was found that TIG had substantial antifungal
      activity against mature C. albicans biofilms. Therefore, TIG was assayed alone
      and in combination with fluconazole (FLC), amphotericin B (AmB) or caspofungin
      (CAS). TIG at 2048 MUg/mL resulted in a >50% reduction in the growth of
      planktonic C. albicans cells. TIG inhibited the formation of biofilms from 128
      MUg/mL. Against mature biofilms, 2048 MUg/mL TIG reduced metabolic activity by
      84.2%. Furthermore, addition of 512 MUg/mL TIG to FLC at all concentrations
      tested provided additional reduction in the metabolic activity of mature
      biofilms. However, this was not superior to 512 MUg/mL TIG alone. TIG at 512
      MUg/mL increased the antifungal effect of lower concentrations of AmB (0.03125
      0.25 MUg/mL), but at 0.03125 MUg/mL and 0.0625 MUg/mL this effect was not
      superior to 512 MUg/mL TIG alone. TIG inhibited the antifungal effect of higher
      concentrations of AmB (>= 2 MUg/mL). TIG at 512 MUg/mL inhibited the antifungal
      activity of CAS at lower concentrations (0.25-8 MUg/mL). These data indicate that
      high-dose TIG is highly active in vitro against planktonic cells, forming
      biofilms and mature biofilms of C. albicans.

PMID- 20685089
TI  - Plasmid-mediated streptomycin and sulfamethoxazole resistance in Shigella
      flexneri 3a.
AB  - Shigellosis is a major cause of diarrhoea-related morbidity and mortality,
      especially in children in developing countries such as India. Recently, it was
      estimated that 91 million individuals worldwide contract shigellosis each year.
      The emergence and dissemination of multidrug-resistant strains of Shigella is now
      an emerging global health problem. During the past two decades, much attention
      was given to re-evaluation of treatment recommendations. In the present study, we
      investigated a clinical strain of Shigella flexneri 3a with multiple drug
      resistance. This strain was resistant to ampicillin, chloramphenicol, co
      trimoxazole (trimethoprim/sulfamethoxazole), nalidixic acid, streptomycin,
      sulfamethoxazole, tetracycline and trimethoprim. However, it was susceptible to
      46.7% of drugs tested, i.e. azithromycin, ceftriaxone, ciprofloxacin, gentamicin,
      kanamycin, norfloxacin and ofloxacin. A 6.3-kb plasmid was cured from this strain
      using acridine orange. Following curing, it was observed that 87% of drug
      resistance loci of S. flexneri 3a are chromosomal and 13% are plasmid-encoded.
      This 6.3-kb plasmid was involved in streptomycin and sulfamethoxazole resistance
      in S. flexneri 3a strain, which was confirmed by the disk diffusion method.
      Clonality was confirmed by pulse-field gel electrophoresis (PFGE). This study
      contributes to our knowledge on acquired drug resistance in one of the most
      common Shigella spp., S. flexneri 3a, which will enable better understanding of
      effective clinical management of shigellosis.

PMID- 20685090
TI  - Antimicrobial activities of LL-37 and its truncated variants against Burkholderia
      thailandensis.
AB  - Antimicrobial peptides (AMPs) are essential host defence molecules found in a
      wide variety of species and are promising antibacterial therapeutic candidates.
      Focusing on the human cathelicidin peptide LL-37, the aim of the present study
      was to explore the mechanisms of action and antimicrobial activities of a library
      of LL-37 fragments using Burkholderia thailandensis E264 as a model. The results
      revealed that IG-19 was the shortest fragment within LL-37 that exhibited
      antibacterial activity. LL-31, missing six residues at the C-terminus of LL-37,
      exhibited the strongest killing effect. Freeze-fracture electron microscopy of
      bacterial cells treated with either LL-37 or LL-31 revealed irregular bacterial
      surfaces with bleb projections, indicating that these peptides disrupted the
      integrity of the membrane. In addition, these peptides induced leakage of cell
      components, including nucleotides and even proteins. Altogether, the results
      obtained indicate the potential of using LL-31 as a new AMP to combat
      Burkholderia spp.

PMID- 20685092
TI  - [The impact of cleft lip and palate on the parent-child relationships].
AB  - Cleft lips and palates (CLPs) are the most common human facial malformations.
      Depending on the ethnic and/or geographical origin of the studied populations,
      they can affect up to 1/500 newborns. The treatment of these patients is
      multidisciplinary because these malformations have not only aesthetic
      consequences but also functional consequences as the phonation, hearing,
      deglutition, mastication and ventilation are altered. These consequences can also
      be psychological since the building of the body image, the way others perceive
      it, is likely to be seriously altered. In Europe there are over 210 reference
      hospitals for children affected by CLP. Besides, about 190 different protocols
      were identified. So far no generic protocol was recognized by the medical
      community as a whole. This discrepancy can be explained by the fact that the
      aesthetic and functional result of a protocol cannot be accurately assessed
      before adulthood when the child's growth is complete. Patients presenting with
      CLP don't usually seem to present with any serious psychological or psychiatric
      pathology. Yet a close review of the related literature shows that disorders are
      actually described: behavioural troubles, anxiety, depression and esthetic
      dissatisfaction with one's face in children as well as in adults. The difficulty
      in interpreting these disorders lies in the various factors that are likely to
      impact this condition (family setting, importance and type of the cleft, surgery
      protocol, growth, social environment). A multidisciplinary examination of the
      face and a careful consideration of concerned families show the importance of the
      psychological context and the risks of a dis-harmonious structuring of the
      parents-child relationships on the child's development. The identification of the
      difficulties faced by these families, depending on the child's age, can be easily
      identified. Of course they can be identified at birth when the family first sees
      the child and later on at each stage of the child's life cycle (when starting at
      kindergarten where the child socializes for the very first time, at the start of
      the first year in primary school where pupils learn how to read and then at the
      start of secondary school which is yet another crucial step for the child due to
      the adolescence period). It is also obvious that an adult affected by CLP has a
      particularly heavy medical history as the patient had to go through various
      treatments and surgical interventions during his childhood and adolescence, which
      is even sometimes maintained at adulthood. Repeated appointments with the
      different specialists involved in their treatment punctuate their life as well as
      their parents'. This medico-surgical setting for facial malformations i.e. the
      features of the patient's face which are largely involved in their interpersonal
      relationships and the expression of emotions can have serious consequences. Most
      children presenting with CLPs and living in France benefit from regular follow-up
      schemes carried out in competent reference centres by a multidisciplinary team
      whose members represent each of the fields of expertise involved in the
      correction of this malformation: infantile and maxillofacial surgery,
      otorhinolaryngology (or ENT), ortho-phony and dentofacial orthopedics. Only the
      two French reference centres benefit from the permanent presence of a
      psychologist. This raises the question whether every care centre should take into
      care these children and their parents' mental health by offering psychological
      support during the course of the therapeutic follow-up scheme for these children,
      and this from an early age on as is recommended by the American Cleft Palate
      Craniofacial Association.

PMID- 20685091
TI  - fMRI BOLD responses to negative stimuli in the prefrontal cortex are dependent on
      levels of recent negative life stress in major depressive disorder.
AB  - It is poorly understood how stressors modulate neurobiological mechanisms that
      may contribute to the heterogeneity of major depressive disorder (MDD).
      Unmedicated patients diagnosed with MDD (n=15) and individually matched healthy
      controls (n=15) completed stress questionnaires and were studied with functional
      magnetic resonance imaging while viewing emotional words. Significant effects of
      recent negative life stressors, but not early life stress/trauma, were observed
      on regional blood oxygen level dependent activity during presentation of negative
      words in patients with MDD. No significant effects of stress on brain activation
      to negative words were found in controls. In MDD patients, positive correlations
      were found bilaterally in orbitofrontal areas 11 l/47/12m, which are involved in
      representing negatively valenced stimuli. Negative correlations were also found
      in the right ventrolateral prefrontal area 45, subgenual cingulate area 25, and
      nucleus accumbens, all of which are implicated in the pathophysiology of MDD.
      Negative memory bias was additionally positively associated with recent negative
      life stress and negatively associated with subgenual cingulate activation,
      suggesting a mechanism by which stress may contribute to these abnormalities. The
      severity of recent negative life stressors is an important modifier of
      neurobiological and cognitive function in MDD and may help explain heterogeneity
      in the disorder.

PMID- 20685093
TI  - IGF-1 levels link estimated glomerular filtration rate to insulin resistance in
      obesity: a study in obese, but metabolically healthy, subjects and obese, insulin
      resistant subjects.
AB  - BACKGROUND AND AIMS: Metabolically healthy but obese (MHO) subjects have a
      favourable cardio-metabolic risk profile, but whether they are also at lower risk
      for kidney dysfunction is still questionable. METHODS AND RESULTS: A total of 106
      MHO, 122 normal-weight and 212 insulin-resistant obese (IRO) subjects were
      stratified on the basis of their insulin sensitivity and body mass index (BMI).
      The CKD-EPI equation was used to estimate glomerular filtration rate (eGFR) and
      ISI index was used to estimate insulin sensitivity. eGFR was significantly lower
      in IRO as compared to MHO subjects after adjusting for age, gender and BMI (P =
      0.008). In a logistic regression model adjusted for age, gender and BMI, IRO
      subjects showed an increased risk of having eGFR in the lowest quartile (odds
      ratio (OR) 1.91, 95% confidence interval (CI) 1.01-3.58; P = 0.04) as compared
      with MHO subjects. This association was maintained when waist, lean body mass,
      blood pressure, HDL cholesterol, triglyceride, fasting glucose and insulin levels
      were additionally included into the model (OR 2.49, 95%CI 1.17-5.27; P = 0.01),
      but its independence was not retained with further inclusion of insulin-like
      growth factor-1 (IGF-1) levels (OR 2.16, 95%CI 0.93-5.04; P = 0.07) No
      differences in eGFR were observed between non-obese and MHO individuals.
      CONCLUSIONS: These results indicate that heterogeneity in obese phenotypes may
      account for conflicting evidence regarding the significance of obesity as a risk
      factor for chronic kidney disease. Our findings suggest that obesity is
      associated with lower kidney function only when insulin sensitivity is reduced,
      and that plasma IGF-1 is likely to be an important mechanism linking the IRO
      phenotype with reduced eGFR.

PMID- 20685094
TI  - Serum levels of adhesion molecules ICAM-1 and VCAM-1 and tissue inhibitor of
      metalloproteinases, TIMP-1, are elevated in patients with autoimmune thyroid
      disorders: relevance to vascular inflammation.
AB  - Serum levels of ICAM-1 (Inter Cellular Adhesion Molecule-1), VCAM-1 (Vascular
      cell Adhesion Molecule-1-I), TIMP-1 (tissue inhibitor of metalloproteinases 1)
      and MMP-9 (Metalloproteinase 9) are well established markers of inflammation. The
      physiopathological link between inflammation, atherosclerosis and autoimmunity is
      well demonstrated. However, serum levels of these biomarkers in patients with
      autoimmune-mediated dysthyroidism, including their evolution after improvement of
      the thyroid disorder have not been assessed. So, we evaluated the circulating
      levels of these markers in autoimmune and in non-autoimmune-mediated dysthyroid
      patients, and their evolution after treatment of thyroid disease. We conducted a
      prospective study to evaluate these markers before and after treatment in
      hyperthyroid patients (n = 33; 28 patients with autoimmune disease), hypothyroid
      patients (n = 38; 33 patients with autoimmune disease) and euthyroid subjects (n
      = 33). At baseline, serum levels of ICAM-1, VCAM-1 and TIMP-1 were significantly
      elevated in patients with hyperthyroidism as compared to euthyroid and
      hypothyroid patients (respectively p = 0.0005 and p < 0.0001). In multivariate
      analysis, the differences remained significant for VCAM-1 and TIMP-1. Median
      levels of ICAM-1, VCAM-1 and TIMP-1 were significantly higher in patients with
      autoimmune-mediated dysthyroidism compared to euthyroid patients (respectively p
      < 0.0001 and p = 0.002). In hyperthyroid patients, ICAM-1, VCAM-1 and TIMP-1
      concentrations fell significantly after they had become euthyroid (respectively p
      = 0.0006; p < 0.0001 and p = 0.0009), although VCAM-1 values remained higher than
      those observed in the control group (p = 0.005). We found that autoimmune
      mediated dysthyroidism were associated with increased peripheral blood
      concentrations of VCAM-1, ICAM-1 and TIMP-1. Whether these biological
      abnormalities translate into increase intima remodelling and atherosclerosis
      remains to be studied.

PMID- 20685095
TI  - Localization of fatty acid binding proteins (FABPs) in the cochlea of mice.
AB  - Various fatty acids (FAs) are involved in many different functions in the
      organism as a source of energy, as essential ingredients of membranous lipids as
      well as intracellular signaling molecules. Intracellular fatty acid binding
      proteins (FABPs) comprise a family of soluble lipid binding proteins with low
      molecular masses and which can make long chain FAs soluble to allow intracellular
      translocation in the aqueous cytosol. To clarify the possible involvement of FAs
      and FABPs in hearing function, the present study investigated the localization of
      FABPs in the cochlea of adult mice using immunohistochemical procedures. Among
      various FABP species, H (heart-type)-FABP was localized in inner and outer pillar
      cells and outer phalangeal cells, while B (brain-type)-FABP was localized in
      border cells and cells of Hensen, and fibrocytes in the spiral limbus and spiral
      prominence. In the spiral ganglion, moderate to low H-FABP immunoreactivity was
      observed in almost all neurons, while B-FABP immunoreactivity was found in
      satellite cells. The discrete localization of the two FABPs in different non
      receptor cells in the Organ of Corti suggests that the FABP species and/or their
      ligands, FAs, play important roles in the regulation of the hearing function.

PMID- 20685096
TI  - Local desynchronization of cellular development within mammalian male germ cell
      clones.
AB  - Mammalian male germ cells go through the process of spermatogenesis as cell
      clones. The members of a clone are joined by intercellular bridges which are
      responsible for synchronizing the spermatogenetic process. The present
      ultrastructural study on pubertal and adult golden hamster and mouse testes,
      however, demonstrates that a strict synchronization of germ cell development is
      not attained by this clonal association in any single instance. Local
      desynchronization is either indicated by intraclonal divergence at the stage of
      the cell cycle of the respective germ cells or it is manifested in clones in
      which single cells are affected by degeneration while other members of the clone
      are not. The results are discussed with a view to a possible significance of
      intraclonal desynchronization of male germ cell development in local impairment
      of spermatogenesis and loss of germ cells.

PMID- 20685097
TI  - Boron regulates mineralized tissue-associated proteins in osteoblasts (MC3T3-E1).
AB  - The aim of this study was to determine the effects of boron (B) on the cell
      survival, proliferation, mineralization and mRNA expression of mineralized tissue
      associated proteins. Additionally, determination of the effects of B on the BMP
      4, -6 and -7 protein levels of pre-osteoblastic cells (MC3T3-E1) was also
      intended. The effects of B (pH 7.0) concentrations (0, 0.1, 1, 10, 100, 1000,
      2000, 4000, 8000 and 10,000 ng/ml) on the survival of the cells were evaluated at
      24 and 96 hrs with MTT assay. To evaluate the proliferation in long term, MC3T3
      E1 cells were treated with different concentrations of B (0, 0.1, 1, 10, 100 and
      1000 ng/ml) and were counted on days 2, 5, and 14. While in short term, decreased
      cell survival rate was observed at 1000 ng/ml and above, at long term no
      statistically significant difference was detected in different B concentrations
      applied. Slight decreases at the proliferation of the B-treated groups were
      determined on days 5 and 14 but one-way analysis of variance revealed that the
      difference was statistically insignificant. In mineralization assay, increased
      mineralized nodules were apparently observed in B treatment (1 and 10 ng/ml
      concentrations) groups. Based on quantitative RT-PCR results, remarkable
      regulation in favor of osteoblastic function for Collagen type I (COL I),
      Osteopontin (OPN), Bone Sialoprotein (BSP), Osteocalcin (OCN) and RunX2 mRNA
      expressions were observed in B treatment groups in comparison with untreated
      control groups. Increased BMP-4, -6 and -7 protein levels were detected at 0.1,
      1, 10 and 100 ng/ml B concentrations. Results of the study suggest that at the
      molecular level B displays important roles on bone metabolism and may find novel
      usages at the regenerative medicine.

PMID- 20685098
TI  - Fortification of sorghum (Sorghum vulgare) and pearl millet (Pennisetum glaucum)
      flour with zinc.
AB  - Deficiency of zinc is believed to be as widespread as that of iron, with equally
      serious consequences. Fortification of staple foods with this mineral is a cost
      effective method that can be used to combat this deficiency. In the present
      study, flours of pearl millet and sorghum were evaluated as vehicles for
      fortification with zinc. Zinc stearate was used as the fortificant, and added at
      a level that provided 5mg Zn/100g flour. The metal chelator EDTA was used as a co
      fortificant, the molar ratio of exogenous Zn:EDTA being 1:1. Bioaccessibility of
      zinc from the fortified flours, both raw and cooked, was determined by an in
      vitro simulated gastrointestinal digestion procedure. The results of the study
      revealed that there were differences among these two flours with respect to the
      feasibility of fortification with zinc. Although fortified pearl millet flour
      provided a higher amount of bioaccessible zinc, this was attributable to the
      presence of EDTA, rather than to the fortified zinc. The benefit of fortification
      with zinc was more evident in sorghum flour, compared to that in pearl millet
      flour, the increase in bioaccessible zinc content being more than 1.5 times
      higher as a result of fortification. Fortified sorghum and pearl millet flours
      were stable during storage for a period of up to 60 days. Thus, millet flours
      seem to be satisfactory candidates for fortification with zinc, and can be
      exploited to address zinc deficiency.

PMID- 20685099
TI  - The emerging role of cytomegalovirus in driving immune senescence: a novel
      therapeutic opportunity for improving health in the elderly.
AB  - Cytomegalovirus infection is very common and leads to the generation of a very
      strong humoral and cellular immune response that is maintained for life and
      appears necessary to control viral replication. This leads to marked alterations
      in the composition of the immune cell repertoire and epidemiological evidence
      shows that this can be associated with increased levels of morbidity and
      mortality in the elderly. The immune response appears to be triggered by frequent
      episodes of subclinical viral reactivation and the predominant effect is of the
      accumulation of large numbers of cytotoxic cells. These observations suggest that
      mechanisms that could serve to control the expansion of this immune response
      could have significant potential in improving the health of elderly donors.

PMID- 20685100
TI  - Retinol inhibits aromatase activity and expression in vitro.
AB  - Aromatase converts androgens into estrogens and is thought to supply a local
      source of estrogen that facilitates the growth of hormone-responsive tumor cells.
      Inhibition of aromatase is therefore an important chemopreventive strategy. We
      investigated the effect of retinol and selected retinoids on the activity and
      expression of aromatase in two human carcinoma cell lines in vitro. Retinol (ROH)
      and all-trans retinoic acid (ATRA) significantly inhibited aromatase activity in
      a concentration-dependent manner in microsomes isolated from JEG-3 human
      placental carcinoma cells, whereas 9-cis and 13-cis retinoic acid had significant
      inhibitory activity only at the highest concentrations tested. Similar results
      were observed in an assay of cellular aromatase activity in MCF-7 human breast
      cancer cells. Enzyme kinetic studies by double-reciprocal plot demonstrated that
      ROH inhibited microsomal aromatase activity in a mixed manner. In addition, ROH
      suppressed both the basal and cAMP-induced expression of aromatase mRNA in MCF-7
      cells and inhibited transcription controlled by a cAMP-responsive element. These
      results suggest that aromatase activity and expression are a molecular target of
      ROH and chemopreventive retinoids, an activity that may underlie, in part, their
      inhibitory effects on hormone-dependent cancer.

PMID- 20685101
TI  - A cone-shaped 3D carbon nanotube probe for neural recording.
AB  - A novel cone-shaped 3D carbon nanotube (CNT) probe is proposed as an electrode
      for applications in neural recording. The electrode consists of CNTs synthesized
      on the cone-shaped Si (cs-Si) tip by catalytic thermal chemical vapor deposition
      (CVD). This probe exhibits a larger CNT surface area with the same footprint area
      and higher spatial resolution of neural recording compared to planar-type CNT
      electrodes. An approach to improve CNT characteristics by O(2) plasma treatment
      to modify the CNT surface will be also presented. Electrochemical
      characterization of O(2) plasma-treated 3D CNT (OT-CNT) probes revealed low
      impedance per unit area (~64.5 Omega mm(-2)) at 1 kHz and high specific
      capacitance per unit area (~2.5 mF cm(-2)). Furthermore, the OT-CNT probes were
      employed to record the neural signals of a crayfish nerve cord. Our findings
      suggest that OT-CNT probes have potential advantages as high spatial resolution
      and superb electrochemical properties which are suitable for neural recording
      applications.

PMID- 20685102
TI  - Intense pulsed light induced platinum-gold alloy formation on carbon nanotubes
      for non-enzymatic glucose detection.
AB  - We demonstrated a novel method for the formation of alloy nano-islands on carbon
      nanotube (CNT). The two metal layers (Pt, Au) were sputtered on CNTs and the
      intense pulsed light (IPL) was irradiated on the metal layers. The absorbed light
      provides enough energy for the diffusion mixing between Pt and Au, forming Pt-Au
      alloy phase. While the alloy is being formed by the IPL irradiation, the metal
      layers are broken into nano-islands on CNT due to the surface energy minimization
      between the metal layers and CNT. The surface characterizations of the Pt-Au/CNT
      were performed with X-ray diffraction, scanning electron microscope, and energy
      dispersive X-ray spectroscopy. Different compositions of alloy nanoparticles were
      obtained by adjusting the deposition thicknesses of Pt and Au on CNT.
      Pt50Au50/CNT electrode showed the highest glucose oxidation current peak among
      Pt, Pt70Au30, Pt50Au50, Pt30Au70, and Au/CNT electrodes while the electroactive
      surface areas of them are kept to be similar (average surface area=7.00 cm2,
      coefficient of variation=0.06). The amperometric response of Pt50Au50/CNT
      electrode to the glucose concentrations showed a wide linear range up to 24.44 mM
      with a high detection sensitivity of 10.71 MUA mM(-1) cm(-2). Reproducibility and
      long-term stability of the Pt-Au/CNT electrode were also proven in the
      experiments.

PMID- 20685103
TI  - Electrochemical determination of carbohydrate-binding proteins using carbohydrate
      stabilized gold nanoparticles and silver enhancement.
AB  - A highly sensitive electrochemical lectin biosensor has been developed for the
      first time using carbohydrate-stabilized gold nanoparticles and silver
      enhancement technique. A target lectin protein, Concanavalin A (Con A), was
      specifically bound to the self-assembled monolayer of thiolated mannose on a gold
      electrode. Mannose-stabilized gold nanoparticles were added to form a sandwich
      type complex with the Con A and were followed by silver-enhancement process to
      coat the mannose-stabilized gold nanoparticles with silver metal. The coated
      metallic silver was dissolved in an acidic solution and the resulting silver ions
      were detected by anodic stripping voltammetry. The present lectin biosensor gave
      a linear response (R(2)=0.999) for Con A concentration from 0.084 MUg/mL to 50.0
      MUg/mL with a remarkable detection limit (S/N=3) of 0.070 MUg/mL, which is much
      lower compared to those obtained with the reported microgravimetric and
      colorimetric detection methods.

PMID- 20685104
TI  - Switchable "On-Off" electrochemical technique for detection of phosphorylation.
AB  - In this paper, we report a simple but ultrasensitive electrochemical method for
      the detection of phosphorylation and the activity of protein kinase A (PKA). In
      this detection system, the substrate peptides form a compact and positively
      charged self-assembly monolayer (SAM) on an electrode surface. It will block the
      positively charged electrochemical probe [Ru(NH3)5Cl]2+ from getting access to
      the electrode, keeping the "Off" state of the detection system. After the
      phosphorylation by the enzyme, the SAM becomes loose due to the generation of
      phosphate groups. Meanwhile, due to the electrostatic interaction between the
      negative phosphate groups and positively charged SAM, [Ru(NH3)5Cl]2+ molecules
      can move and get close to the electrode surface. As a result, electrochemical
      signal is observed and the system is at "On" state. Furthermore, the switch
      between the "On" and "Off" states can be achieved by the catalysis of PKA and
      alkaline phosphatase, respectively. The electrochemical response can be used to
      assay the PKA activity with an extraordinarily low detection limit of 1*10(-4)
      unit/mL and wide linear range from 1*10(-4) to 1*10(-2) unit/mL. This assay can
      also be performed by using serum samples with high specificity and
      reproducibility.

PMID- 20685105
TI  - Direct voltammetric sensing of L-cysteine at pristine GaN nanowires electrode.
AB  - The study demonstrates an electrochemical approach for direct sensing of L
      Cysteine at gallium nitride nanowires (GaNNWs), a wide band gap semiconductor
      possessing 1-dimensional nanomaterial-specific high surface-sensitivity and
      unusually high surface-conductivity. Pristine GaNNWs can respond to L-Cysteine
      oxidation without any surface-modification: a unique advantage compared with
      other common electrodes. Cyclic voltammetric investigations on the effects of pH
      and potential-scan rate reveal an electrocatalytic oxidation of L-Cysteine
      controlled by the electroactive L-CyS(-) species. Advantages of direct L-Cysteine
      oxidation at surface-dominated GaNNWs electrodes can achieve an optimum
      sensitivity of 42 nA/MUM with an experimental detection limit of 0.5 MUM, over
      0.5-75 MUM dynamic range, under physiological condition (pH=7.4).

PMID- 20685106
TI  - 15-MUm-sized single-cellular-level and cell-manipulatable microplasma jet in
      cancer therapies.
AB  - The authors describe a proposed 15-MUm-sized, single-cellular-level, and cell
      manipulatable microplasma jet device with a microcapillary glass tip and its
      potential in the development of cancer treatment therapies. The electrical and
      optical properties of the plasma jets and preliminary apoptosis results of
      cultured murine tumor cells and non-tumor fibroblast cells treated with the
      plasma jets are presented. The generated plasma jet was stable and enabled the
      treatment of cultured cells in cell culture plates regardless of the small inner
      diameter and low gas flow rate. The microplasma jet was observed inducing
      apoptosis in cultured murine melanoma tumor cells in a dose-dependent manner.
      Furthermore, the percentage of apoptotic cells of murine melanoma tumor cells
      induced by this plasma device was approximately 2.5 times bigger than that of
      murine fibroblast cells as indicated by an Annex V apoptosis assay. The apoptosis
      in cultured murine tumor cells by the 15-MUm-sized single-cellular-level and cell
      manipulatable microplasma jet device was also observed using an in situ apoptosis
      assay. We report on a novel microplasma jet device with the advantages of single
      cellular-level and single cell-manipulatable plasma treatment with precise and
      solid stimuli. This highly precise plasma medicine, which enables new directed
      cancer therapies can be combined with current cell manipulation and cell
      culturing technologies without much difficulty.

PMID- 20685107
TI  - An optical microbial biosensor for detection of methyl parathion using
      Sphingomonas sp. immobilized on microplate as a reusable biocomponent.
AB  - Organophosphorus pesticides such as methyl parathion have been widely used in the
      field of agriculture for insect pest control. These pesticides and their
      degradation products cause environmental pollution and ecological problem. With a
      view to monitor these pesticides biosensors are being developed. A bacterium
      Sphingomonas sp. from field soil has been isolated and identified in our
      laboratory that hydrolyzes the methyl parathion upto a chromophoric product, p
      nitrophenol (PNP). PNP can be detected by electrochemical and colorimetric
      methods, which can be exploited to develop a biosensor for detection of the
      organophosphate pesticide. Whole cells of Sphingomonas bacteria were immobilized
      directly onto the surface of the wells of polystyrene microplates (96 wells)
      using glutaraldehyde as the cross-linker. SEM study confirmed the immobilization
      of Sphingomonas sp. Immobilized bacterial microplate was associated directly with
      the optical transducer, microplate reader. The microplate-based biosensor is
      having advantages as it has 96 reaction vessels and therefore it provides a
      convenient system for detecting multiple numbers of samples in a single platform.
      Detection range of the biosensor from the linear range was determined to be 4-80
      MUM methyl parathion. Cells-immobilized microplates were having reusability upto
      75 reactions. Present study reports an innovative concept where the microplate
      can be used as immobilizing support for development of reusable microbial
      biocomponent.

PMID- 20685108
TI  - A quartz crystal microbalance sensor based on mussel-inspired molecularly
      imprinted polymer.
AB  - In this work, we describe a simple, inexpensive and fast method for the
      generation of molecularly imprinted polymer (MIP) film on quartz crystal
      microbalance (QCM) crystals using mussel-inspired polymer. Commonly known as a
      neurotransmitter, dopamine is also a small-molecule mimic of the adhesive
      proteins of mussels. Polymerization of dopamine in the presence of template
      molecule (1,3,5-pentanetricarboxylic acid, an analogue of domoic acid, in this
      case) could produce an adherent molecularly imprinted polydopamine film coating
      on QCM crystals. Advantages, such as high hydrophilicity, high biocompatibility
      and controllable thickness, make this molecularly imprinted polydopamine film an
      attractive recognition element for sensors. Selective rebinding of domoic acid on
      mussel-inspired molecularly imprinted polymer (m-MIP) coated crystal was observed
      as a frequency shift quantified by piezoelectric microgravimetry with the QCM
      system. The decreasing frequency shows a good linear relationship with the
      concentration of domoic acid. The quantitation limit of domoic acid was 5 ppb
      with the linear range of 0-100 ppb. The QCM sensor has high selectivity and was
      able to distinguish domoic acid from its analogous p-phthalic acid and o-phthalic
      acid owing to the molecular imprinting effect. In addition, the practical
      analytical performance of the sensor was examined by evaluating the detection of
      domoic acid in mussel extracts with satisfactory results. It is envisaged that m
      MIP could be suitable as recognition element for sensors and the proposed m-MIP
      QCM sensor could be employed to detect analyte of interest in complex matrices.

PMID- 20685109
TI  - Simultaneous carbon and nitrogen removal using an oxic/anoxic-biocathode
      microbial fuel cells coupled system.
AB  - A coupled microbial fuel cell (MFC) system comprising of an oxic-biocathode MFC
      (O-MFC) and an anoxic-biocathode MFC (A-MFC) was implemented for simultaneous
      removal of carbon and nitrogen from a synthetic wastewater. The chemical oxygen
      demand (COD) of the influent was mainly reduced at the anodes of the two MFCs;
      ammonium was oxidized to nitrate in the O-MFC's cathode, and nitrate was
      electrochemically denitrified in the A-MFC's cathode. The coupled MFC system
      reached power densities of 14 W/m(3) net cathodic compartment (NCC) and 7.2
      W/m(3) NCC for the O-MFC and the A-MFC, respectively. In addition, the MFC system
      obtained a maximum COD, NH(4)(+)-N and TN removal rate of 98.8%, 97.4% and 97.3%,
      respectively, at an A-MFC external resistance of 5 Omega, a recirculation ratio
      (recirculated flow to total influent flow) of 2:1, and an influent flow ratio (O
      MFC anode flow to A-MFC anode flow) of 1:1.

PMID- 20685110
TI  - Self-consistent liquid-to-gas mass transfer calculations.
AB  - This work develops an alternative gas transfer calculation method to the two
      methods currently used in anaerobic digestion modelling. The current calculation
      methods are problematic because one is computationally stiff, while the other
      introduces an artificial overpressure. The new approach began by noting that the
      gas partial pressures are the same as the partial flows at the liquid/gas
      interface, and then used the self-consistency requirement to develop gas pressure
      equations which were used by a search algorithm. The new approach took about
      three iterations to achieve a flow precision better than 2x10(-7) mol h(-1) l(
      1), and was self-consistent and stable even when working with eight gases.

PMID- 20685111
TI  - Conidia immobilization of T-DNA inserted Trichoderma atroviride mutant AMT-28
      with dichlorvos degradation ability and exploration of biodegradation mechanism.
AB  - An immobilizing conidia approach was used to study the degradation ability of
      dichlorvos in Trichoderma atroviride T-DNA insertional mutant AMT-28. Beads with
      10(7) immobilized conidia per 100 mL of Na-alginate solution exhibited the
      highest degradation abilities. The immobilized conidia showed enhanced
      degradation abilities compared with immobilized or freely suspended mycelia. The
      immobilized cells kept good storage capacity and reusability. Dichlorvos was
      confirmed to be completely removed by mycelia of AMT-28 within 7 days using HPLC
      analysis. The dichlorvos degradation rates in auxotrophic Burk media varied and
      were significantly affected by nitrogen sources. There was no detectable
      biosorption and the removal of dichlorvos in AMT-28 was primarily attributed to a
      kind of Biomineralization process.

PMID- 20685112
TI  - Seasonal variation in the chemical composition of the bioenergy feedstock
      Laminaria digitata for thermochemical conversion.
AB  - To avoid negative impacts on food production, novel non-food biofuel feedstocks
      need to be identified and utilised. One option is to utilise marine biomass,
      notably fast-growing, large marine 'plants' such as the macroalgal kelps. This
      paper reports on the changing composition of Laminaria digitata throughout it
      growth cycle as determined by new technologies. The potential of Laminaria sp. as
      a feedstock for biofuel production and future biorefining possibilities was
      assessed through proximate and ultimate analysis, initial pyrolysis rates using
      thermo-gravimetric analysis (TGA), metals content and pyrolysis gas
      chromatography-mass spectrometry. Samples harvested in March contained the lowest
      proportion of carbohydrate and the highest ash and alkali metal content, whereas
      samples harvested in July contained the highest proportions of carbohydrate,
      lowest alkali metals and ash content. July was therefore considered the most
      suitable month for harvesting kelp biomass for thermochemical conversion to
      biofuels.

PMID- 20685113
TI  - Empirical modelling and dual-performance optimisation of a hydrogen sulphide
      removal process for biogas treatment.
AB  - This study was conducted in order to investigate the use of a simple, low-cost
      technology for the removal of hydrogen sulphide (H(2)S) from biogas, consisting
      of an anoxic biotrickling filter. Modelling and optimisation of the process was
      achieved by studying two independent variables (H(2)S concentration and biogas
      flowrate) and two simultaneous performance criteria (H(2)S removal efficiency (%)
      and H(2)S loading rate (g/(m(3) bed day)), which were inversely related. The
      experiments were carried out on a bioreactor with a 12 L packing volume. H(2)S
      concentration and biogas flowrate were varied in the range of 2000-4000 ppm(v)
      and 10-70 L/h, respectively. A model sensitivity analysis indicated the influence
      of the process variables on the bioreactor performance. Process optimisation was
      undertaken on a H(2)S removal efficiency basis, while maintaining a target H(2)S
      loading rate, depending on the desired quality for the biogas use and the
      technological requirements.

PMID- 20685114
TI  - Influence of diatomite addition on membrane fouling and performance in a
      submerged membrane bioreactor.
AB  - This paper examined the effect of diatomite addition on membrane fouling and
      process performance in an anoxic/oxic submerged membrane bioreactor (A/O MBR).
      Particle size distribution, molecular weight distribution and microbial activity
      have been investigated to characterize the sludge mixed liquor. Results show that
      diatomite addition is a reliable and effective approach in terms of both membrane
      fouling mitigation and pollutants removal improvement. The MBR system with
      diatomite addition of 50 mg/L enhanced the removal of COD, TN and TP by 0.9%,
      6.9% and 31.2%, respectively, as compared to the control MBR (without diatomite
      addition). The NH(4)-N removal always maintained at a high level of over 98%
      irrespective of diatomite addition. Due to the hybrid effect of adsorption and co
      precipitation on fine colloids and dissolved organic matter (DOM) from the
      addition of diatomite, a reduction in foulants amount, an increase in microbial
      floc size and an improvement in sludge settleability have been achieved
      simultaneously. As a result, the membrane fouling rate was mitigated
      successfully.

PMID- 20685115
TI  - Evaluation of metal ions (Zn(2+), Fe(3+) and Mg(2+)) effect on the production of
      fusaricidin-type antifungal compounds by Paenibacillus polymyxa SQR-21.
AB  - Effect of metal ions (Mg(2+), Zn(2+) and Fe(3+)) on the production of fusaricidin
      type antifungal compounds by Paenibacillus polymyxa SQR-21 was studied in liquid
      culture. First, one-factor; three-level experiments were conducted to find out
      optimal concentrations of each metal ion for maximum production of fusaricidins.
      Later, three-factor; five-level experiments were performed and a quadratic
      predictive model was developed using response surface methodology (RSM). The
      results indicated that Fe(3+) and Mg(2+) positively affected the growth of P.
      polymyxa as determined by measuring the OD(600) of the liquid culture. The
      production of fusaricidin-type antifungal compounds was significantly inhibited
      by Zn(2+) (P=0.0114) and increased by Mg(2+) (P=0.0051) but the effect of Fe(3+)
      (P=0.2157) was non-significant. However, a synergistic positive effect of Mg(2+)
      and Fe(3+) on the production of antifungal compounds was observed. This study
      sheds lights on the pertinent effects of the individual and combined metal ions
      on the production of fusaricidins in P. polymyxa. It provides the key information
      for optimization of the metal ions in the fermentation media to achieve the
      maximum antibiotic production in this strain.

PMID- 20685116
TI  - Effect of the ash on enzymatic hydrolysis of steam-exploded rice straw.
AB  - The effect of metal ions in ash on enzymatic hydrolysis of crop straw has not
      attracted sufficient attention. In present study, rice straw with high ash
      content was taken as an example to study the effect. It was found that the common
      cations of ash (K(+), Mg(2+), Ca(2+), Al(3+), Mn(2+), Fe(3+), Cu(2+), and Zn(2+))
      all showed inhibitive effects on cellulase at different levels, except for the
      stimulative effects of Ca(2+) and Mg(2+) on beta-glucosidase. Interestingly,
      washing treatment, combined with steam explosion, could effectively remove the
      ash cations of rice straw. The kinetic study of enzymatic hydrolysis indicated
      that, compared with the unwashed steam-exploded rice straw (SERS), the maximal
      hydrolysis velocity of washed SERS was increased by 12.5%. Therefore, the removal
      of ash by washing could facilitate the enzymatic hydrolysis of SERS.

PMID- 20685117
TI  - Discovery of potent HIV integrase inhibitors active against raltegravir resistant
      viruses.
AB  - A series of novel HIV integrase inhibitors active against rategravir resistant
      strains are reported. Initial SAR studies revealed that activities against wild
      type virus were successfully maintained at single digit nanomolar level with a
      wide range of substitutions. However, inclusion of nitrogen-based cyclic
      substitutions was crucial for achieving potency against mutant viruses. Several
      compounds with excellent activities against wild-type virus as well as against
      the viruses with the mutations Q148H/G140S or N155H/E92Q were reported.

PMID- 20685118
TI  - The synthesis and structure-activity relationship of 4-benzimidazolyl
      piperidinylcarbonyl-piperidine analogs as histamine H3 antagonists.
AB  - A structure-activity relationship study of the lead piperazinylcarbonylpiperidine
      compound 3 resulted in the identification of 4-benzimidazolyl-piperidinylcarbonyl
      piperidine 6h as a histamine-3 (H(3)) receptor antagonist. Additional
      optimization of 6h led to the identification of compounds 11i-k with K(i) <or=
      0.5 nM and good in vivo activity.

PMID- 20685119
TI  - Penta-substituted benzimidazoles as potent antagonists of the calcium-sensing
      receptor (CaSR-antagonists).
AB  - A series of novel benzimidazole derivatives has been designed via a scaffold
      morphing approach based on known calcilytics chemotypes. Subsequent lead
      optimisation led to the discovery of penta-substituted benzimidazoles that
      exhibit attractive in vitro and in vivo calcium-sensing receptor (CaSR)
      inhibitory profiles. In addition, synthesis and structure-activity relationship
      data are provided.

PMID- 20685120
TI  - Synthesis of pyrrolomorphinan derivatives as kappa opioid agonists.
AB  - We synthesized pyrrolomorphinan derivatives 6, 7, and 9 to examine whether the
      pyrrole ring would be an accessory site in the kappa opioid receptor selective
      antagonist, nor-binaltorphimine. Derivative 6 had an alpha,beta-unsaturated
      ketone substituent that strongly bound to the kappa receptor. The compound with
      the highest kappa receptor selectivity, 6e, produced a dose-dependent
      antinociceptive effect in the mouse acetic acid writhing test. However,
      derivatives 7 and 9, which did not have alpha,beta-unsaturated ketone
      substituents, showed less kappa receptor selectivity than compound 6. Based on
      structure-activity relationships, we proposed that these compounds adopted active
      structures for kappa selective agonist activity. The pyrrole ring would not
      function as an accessory site, but the ability of the side chain on the pyrrole
      ring to localize above the C-ring appeared to confer kappa selective agonist
      activity. These results will promote the design of novel kappa agonists.

PMID- 20685121
TI  - Yeast vacuoles: more than a model lysosome.
AB  - Thanks to their amenability to both genetic and biochemical analysis, vacuoles of
      S. cerevisiae are valuable models for trafficking processes to mammalian
      lysosomes. They also have additional functions to lysosomes, and all of these
      processes can influence the size and number of vacuoles. Several recent papers
      have indicated that some vacuolar proteins participate in more than one process,
      and hence could be regulatory points to balance the processes and control vacuole
      dimensions. Studies of vacuoles from other yeasts and fungi are uncovering
      further roles for vacuoles, increasing the apparent requirement for such
      regulation. Having served as models in the past, yeast vacuoles are now well
      suited to develop the next generation of quantitative methods to understand
      organelle functions and dynamics.

PMID- 20685122
TI  - Aquaporin-4 in glioma invasion and an analysis of molecular mechanisms.
AB  - Aquaporin-4 (AQP4) is the most important member of the aquaporin (AQP) family in
      the central nervous system and has a key role in maintaining water and ion
      homeostasis. It is clear that AQP4 participates in brain edema after injury and
      other brain diseases. Various studies report that AQP4 is significantly up
      regulated in glioblastoma multiforme compared to low-grade glioma and normal
      brain tissue, suggesting that it might be involved in tumor malignancy as well as
      regulation of brain edema. Recent discoveries of AQP4 involvement in cell
      migration and cytoskeleton organization suggest that AQP4 has a critical role in
      glioma malignancy. This review focuses on the newly discovered functions and
      molecular mechanisms of AQP4 in infiltrative gliomas.

PMID- 20685123
TI  - Fast signals and slow marks: the dynamics of histone modifications.
AB  - Most multi-cellular organisms adopt a specific gene expression pattern during
      cellular differentiation. Once established, this pattern is frequently maintained
      over several cell divisions despite the fact that the initiating signal is no
      longer present. Differential packaging into chromatin is one such mechanism that
      allows fixation of transcriptional activity. Recent genome-wide studies
      demonstrate that actively transcribed regions are characterized by a specific
      modification pattern of histones, the main protein component of chromatin. These
      findings support the hypothesis that a histone code uses histone post
      translational modifications to stably inscribe particular chromatin structures
      into the genome. Experiments on the dynamics of histone modifications reveal a
      striking kinetic difference between methylation, phosphorylation and acetylation,
      suggesting different roles of these modifications in epigenetically fixing
      specific gene expression patterns.

PMID- 20685124
TI  - Radiosynthesis and in vivo evaluation of [(11)C]MC80 for P-glycoprotein imaging.
AB  - P-glycoprotein (P-gp) is an ATP-dependent efflux pump protecting the body against
      xenobiotics. The in vitro characterized modulator 6,7-dimethoxy-2-(6-methoxy
      naphthalen-2-ylmethyl)-1,2,3,4-tetrahydroisoquinoline (MC80) of the P-gp pump was
      labelled with (11)C and evaluated in vivo for its potential to image P-gp
      function and expression. Radiochemical pure (>98%) [(11)C]MC80 was obtained
      within 25 min starting from [(11)C]methyl iodide with radiochemical yield of 26%.
      Biodistribution studies in FVB mice demonstrated a high baseline brain uptake
      (7.66 + or - 1.38%ID/g at 1 min pi). Cerebral uptake was increased in mdr1a knock
      out mice as well as after CsA pretreatment. Pre-administration of an excess of
      non-radioactive MC80 caused a reduced uptake in several target organs including
      brain, pancreas and intestines. The results indicate that [(11)C]MC80 kinetics
      are modulated by P-gp. Reversed phase-HPLC analysis of brain revealed an
      excellent metabolic profile (>90% intact [(11)C]MC80).

PMID- 20685125
TI  - Potential anti-inflammatory phenolic glycosides from the medicinal plant Moringa
      oleifera fruits.
AB  - Bioassay-guided isolation and purification of the ethyl acetate extract of
      Moringa oleifera fruits yielded three new phenolic glycosides; 4-[(2'-O-acetyl
      alpha-l-rhamnosyloxy) benzyl]isothiocyanate (1), 4-[(3'-O-acetyl-alpha-l
      rhamnosyloxy)benzyl]isothiocyanate (2), and S-methyl-N-{4-[(alpha-l
      rhamnosyloxy)benzyl]}thiocarbamate (3), together with five known phenolic
      glycosides (4-8). The structures of the new metabolites were determined on the
      basis of spectroscopic analyses including 1D- and 2D-NMR and mass spectrometry.
      The anti-inflammatory activity of isolated compounds was investigated with the
      lipopolysaccharide (LPS)-induced murine macrophage RAW 264.7 cell line. It was
      found that 4-[(2'-O-acetyl-alpha-l-rhamnosyloxy)benzyl]isothiocyanate (1)
      possessed potent NO-inhibitory activity with an IC(50) value of 1.67 microM,
      followed by 2 (IC(50)=2.66 microM), 4 (IC(50)=2.71 microM), and 5 (IC(50)=14.4
      microM), respectively. Western blots demonstrated these compounds reduced LPS
      mediated iNOS expression. In the concentration range of the IC(50) values, no
      significant cytotoxicity was noted. Structure-activity relationships following NO
      release indicated: (1) the isothiocyanate group was essential for activity, (2)
      acetylation of the isothiocyanate derivatives at C-2' or at C-3' of rhamnose led
      to higher activity, (3) un-acetylated isothiocyanate derivatives displayed eight
      times less activity than the acetylated derivatives, and (4) acetylation of the
      thiocarbamate derivatives enhanced activity. These data indicate compounds 1, 2,
      4 and 5 are responsible for the reported NO-inhibitory effect of Moringa oleifera
      fruits, and further studies are warranted.

PMID- 20685126
TI  - Antiviral agents 2. Synthesis of trimeric naphthoquinone analogues of conocurvone
      and their antiviral evaluation against HIV.
AB  - The synthesis of a new series of conocurvone analogues is presented that explores
      the importance of the pyran rings of conocurvone, their degree of unsaturation as
      well as the role of alkoxy functionalities as pyran ring replacements, for the
      inhibition of the HIV-1 integrase (IN) enzyme. Difficulties in synthesising a
      trimeric naphthoquinone where the central quinone bears a peri-dihydropyran ring
      was attributed to distortion of the electrophilic dihaloquinone successfully
      utilised in the past. Increased electron density could also be a factor in
      reducing reactivity. The desired central dihydropyran bearing trimeric
      naphthoquinone was successfully synthesised by using a more reactive bromo
      tosyloxyquinone intermediate. A maleimide derivative, where the central quinone
      between the pendant hydroxyquinones was replaced, was successfully synthesised
      and although it exhibited comparable enzyme inhibitory activity it had negligible
      HIV inhibitory cellular activity. Compounds were assessed for activity in both in
      vitro assays using purified recombinant HIV-1 IN and demonstrated superior or
      comparable activity to conocurvone derivatives previously reported.

PMID- 20685127
TI  - Problems in polarized light microscopy observation of birefringence of calcium
      pyrophosphate dihydrate crystals.
AB  - To reconsider the problems arising from the use of the phase plate as a test
      plate inserted into a polarized light microscope system for the analysis of
      triclinic calcium pyrophosphate dihydrate (t-CPPD) crystals, or Ca(2)P(2)O(7) x
      2H(2)O in the synovial fluid of arthritis patients, we made the polarized light
      microscopy observations using a phase plate with a retardation of 530 nm for the
      synthesized t-CPPD crystals well-characterized by X-ray powder pattern indexing
      and single crystal X-ray diffraction measurements. The microscopy observations
      were made of crystals of different sizes, thicknesses and shapes. The retardation
      was assessed using the interference color chart at four extinction and diagonal
      positions both with and without the test plate. The addition and subtraction
      states produced by superimposing the retardations of two anisotropic materials,
      that is, the t-CPPD crystal and the 530 nm phase plate, were deduced from the
      interference color change by inserting the test plate at four diagonal positions.
      When the color change of a crystal at a diagonal position resulting from 90
      degree rotation exhibits no clear birefringence, the interference color chart was
      shown to be useless. We suggested the use of a compensator whose retardation can
      be changed to obtain an accurate value for the retardation of the crystal.

PMID- 20685128
TI  - Gamma spectrometry and chemical characterization of ceramic seeds with samarium
      153 and holmium-166 for brachytherapy proposal.
AB  - Ceramic seeds were synthesized by the sol-gel technique with Si:Sm:Ca and
      Si:Ho:Ca. One set of seeds was irradiated in the TRIGA type nuclear reactor IPR
      R1 and submitted to instrumental neutron activation analysis (INAA), K(0) method,
      to determine mass percentage concentration of natural samarium and holmium in the
      seed as well as to determine all existing radionuclides and their activities.
      Attention was paid to discrimination of Si-31, Ca-40, Ca-45, Ca-47, Ca-49, Sm
      145, Sm-155, Sm-153 and Ho-166. A second sample was submitted to atomic emission
      spectrometry (ICP-AES) also to determine samarium and holmium concentrations in
      weight. A third sample was submitted to X-ray fluorescence spectrometry to
      qualitatively determine chemical composition. The measured activity was due to Sm
      153 and Ho-166 with a well-characterized gamma spectrum. The X-ray fluorescence
      spectrum demonstrated that there is no discrepancy in seed composition. The
      maximum ranges in the water of beta particles from Sm-153 and Ho-166 decay were
      evaluated, as well as the dose rate and total dose delivered within the volume
      delimited by the range of the beta particles. The results are relevant for
      investigation of the viability of producing Sm-153 and Ho-166 radioactive seeds
      for use in brachytherapy.

PMID- 20685129
TI  - Design and performance evaluation of single-use whole-sterile "plug & play" kits
      for routine automated production of [(11)C]choline and [(11)C]methionine with
      radiopharmaceutical quality.
AB  - We herein describe the design and performance evaluation of single-use whole
      sterile "plug & play" kits for routine automated production of [(11)C]methionine
      and [(11)C]choline for human use. Kits were designed for maximal simplicity and
      ease of using modules from Eckert & Ziegler Modular Lab System. The use of all
      disposable sterile medical-grade material, helps ensure safety and cGMP
      compliance. The quick set-up and removal ("plug & play") also reduces radiation
      burden to operator.

PMID- 20685130
TI  - Can first cycle CBCs predict older patients at very low risk of neutropenia
      during further chemotherapy?
AB  - Elderly cancer patients with normal complete blood cell counts (CBCs) during the
      first course of (some types of) chemotherapy might be unlikely to experience
      grade 4 neutropenia during subsequent cycles. In this case, further weekly CBCs
      might be avoided. We used data of 223 cancer patients aged 70+ who were included
      in the CRASH (Chemotherapy Risk Assessment Score for High-age patients) trial
      between 2003 and 2007 in 7 cancer practices in the US. First cycle CBC values
      were compared to subsequent cycles. MAX2-score was used as a measure for toxicity
      of the chemotherapy regimen. Sixty-two patients (28%) experienced grade 4
      neutropenia during subsequent cycles. Among patients who received chemotherapy
      with a MAX2-score lower than 0.20, only 4.6% of those without neutropenia during
      the first cycle experienced grade 4 neutropenia during subsequent cycles. Weekly
      CBC might be avoided in these patients receiving chemotherapy. Future prospective
      studies should confirm these results.

PMID- 20685131
TI  - The significance of early, major and stable molecular responses in chronic
      myeloid leukemia in the imatinib era.
AB  - Tyrosine kinase inhibitors (TKI) have dramatically changed the management and the
      outcome of chronic myeloid leukemia (CML) patients. Imatinib is recognized as
      gold standard first-line therapy and impressive clinical and cytogenetic
      responses are obtained in the majority of chronic phase patients treated with
      this drug. Quantitative polymerase chain reaction (RQ-PCR) tool is used to
      monitor molecular residual disease, but practical issues are associated to
      measurement of molecular responses. Several evidences have now proved that
      molecular responses have prognostic significance: patients who achieve early
      molecular response are more likely to obtain durable cytogenetic response and to
      present less rate of disease progression. While some reports indicated that
      achieving major molecular response (MMR) represents the most important endpoint
      associated to best outcome, some other reports indicated that achievement of MMR
      does not improve the greatest clinical benefit brought by complete cytogenetic
      response. In this review, we discuss on the role of molecular monitoring, the
      significance of early response and its correlation with outcome, the significance
      of major and complete molecular response, the emphasized value of a stable
      molecular response, the early identification of resistance presenting with
      increased molecular level.

PMID- 20685132
TI  - Investigating the effect of mixing ratio on molar mass distributions of synthetic
      polymers determined by MALDI-TOF mass spectrometry using design of experiments.
AB  - It is well known that the mixing ratio affects the molar mass distribution of
      synthetic polymers determined by matrix-assisted laser desorption/ionization time
      of-flight mass spectrometry (MALDI-TOF MS). Surely, the molar mixing ratio
      determines whether a mass spectrum will be obtained or not. However, depending on
      the mass range, several effects such as multimer formation occur, which might be
      a source of errors in molar mass distribution calculations. In this study, the
      effect of mixing ratio was investigated for several synthetic polymers, including
      polystyrene (PS), poly(dimethylsiloxane) (PDMS), poly(ethylene glycol) (PEG), and
      poly(methyl methacrylate) (PMMA) using statistical designs of experiments. The
      2(3) full factorial design was found to be suitable in the study of more than
      1000 samples. The obtained MALDI mass spectra as well as the ANOVA statistics
      show that the mixing ratio affects the molar mass distribution. The optimal
      mixing ratio for a defined synthetic polymer depends on the studied combination
      (matrix, cationization reagent, solvent).

PMID- 20685133
TI  - Mass spectrometry guided in situ proteolysis to obtain crystals for X-ray
      structure determination.
AB  - A strategy for increasing the efficiency of protein crystallization/structure
      determination with mass spectrometry has been developed. This approach combines
      insights from limited proteolysis/mass spectrometry and crystallization via in
      situ proteolysis. The procedure seeks to identify protease-resistant polypeptide
      chain segments from purified proteins on the time-scale of crystal formation, and
      subsequently crystallizing the target protein in the presence of the optimal
      protease at the right relative concentration. We report our experience with 10
      proteins of unknown structure, two of which yielded high-resolution X-ray
      structures. The advantage of this approach comes from its ability to select only
      those structure determination candidates that are likely to benefit from
      application of in situ proteolysis, using conditions most likely to result in
      formation of a stable proteolytic digestion product suitable for crystallization.

PMID- 20685134
TI  - Successes and failures: Worldwide vaccine development and application.
AB  - The impact that vaccines have had on world health has been great. The misery
      prevented and the lives saved have been impressive. But all has not been good. As
      one looks at the success, one can also see the missed opportunities. This
      discussion takes a broad, worldwide view of vaccines--from early research,
      through development and application. It examines our successes and our failures
      and looks with great optimism towards a future having great potential to prevent
      much of today's suffering from infectious diseases.

PMID- 20685135
TI  - Effectiveness of endovascular embolization with a collagen-based embolic agent
      (Marsembol) in an animal model.
AB  - PURPOSE: To investigate in a porcine experimental model the effectiveness, tissue
      penetration, and histologic impact of renal artery embolization with a collagen
      based nonadhesive embolic agent, marsembol. MATERIALS AND METHODS: Fifteen pigs
      underwent embolization of one interlobular artery of the renal artery with
      collagen-resorcinol gel emulsified with Lipiodol and further polymerized with
      glutaraldehyde-formaldehyde mixture. Angiograms were obtained before, during, and
      after the procedure. Animals were euthanized at day 0 (n = 3), 1 week (n = 3), or
      3 months (n = 7), and flat-panel three-dimensional rotational radiologic images
      of the kidneys were obtained. Arterial, medullary, and cortical samples were
      taken for histologic and scanning electron microscopic investigations. RESULTS:
      Fifteen interlobular renal arteries were successfully embolized by delivering 1.7
      mL + or - 0.2 of the embolic agent. All the embolized arteries remained occluded
      at 3 months, leading to a major atrophy of the embolized portions of the kidneys.
      Imaging and histologic findings show that the embolic agent provided a distal
      vessel occlusion and entirely filled the lumen of the arteries up to the
      glomerular tufts. The homogeneous plug formed by the embolic agent induces very
      few inflammatory responses. The regenerative tubular processes were arrested at 3
      months. CONCLUSIONS: The collagen-based embolic agent described here has the
      properties required to perform embolization. These specific properties lead to
      very distal vessel embolization. The embolic agent is effective at 3 months in
      renal embolization.

PMID- 20685136
TI  - Effect of uterine artery embolization on uterine and leiomyoma perfusion:
      evidence of transient myometrial ischemia on magnetic resonance imaging.
AB  - PURPOSE: To document immediate and short-term changes in uterine perfusion after
      uterine artery embolization (UAE). MATERIALS AND METHODS: Fifteen patients
      (median age, 42 years) underwent UAE with tris-acryl gelatin microspheres and a
      limited embolization protocol. Contrast-enhanced magnetic resonance imaging was
      performed before therapy and 1 hour (immediate), 48-72 hours (subacute), and a
      median of 5 months (short-term follow-up) after UAE to determine uterine and
      leiomyoma perfusion. Leiomyomas with a minimum diameter of 10 mm were included.
      Changes in regional (ie, fundus/body/cervix), zonal (ie, endometrium/inner/middle
      and outer myometrial layer), and leiomyoma perfusion were documented. RESULTS:
      UAE was technically successful in all patients. Immediate contrast-enhanced MR
      imaging revealed ischemia of the uterine body and fundus. The endometrium and
      inner myometrial layer was involved in all 15 patients; the middle layer was also
      involved in 13. Ischemic defects were seen in the outer layer in one patient but
      never in the cervix. Subacute follow-up showed reperfusion of the myometrium in
      73% of patients. Ischemic defects occurred in the endometrial and junctional zone
      in four patients and in the middle zone in one. Five-month follow-up showed
      perfusion of all uterine layers in all patients. Ten patients had complete
      infarction of all leiomyomas; five presented with 11 partially perfused
      leiomyomas. CONCLUSIONS: Limited bilateral UAE leads to transient uterine
      ischemia, particularly involving the endometrium and inner and middle zone of the
      myometrium of the uterine body and fundus. The cervix and subserosal layer are
      spared. Complete reperfusion of myometrial tissue is observed within 48-72 hours
      in most cases, whereas ischemic leiomyomas undergo irreversible infarction.

PMID- 20685137
TI  - Role of advanced glycation end product receptors in the pathogenesis of diabetic
      retinopathy.
AB  - PROBLEM: Advanced glycation end products (AGEs) and the interaction with their
      receptors (RAGE) play an important role in the pathogenesis of diabetic
      retinopathy (DR). Our study investigated whether serum soluble (s) RAGE (sRAGE)
      could serve as a prognostic tool for identifying the susceptibility to DR.
      Moreover, we examined the association between soluble forms of vascular cell
      adhesion molecules (sVCAM-1), nitric oxide (NO) and sRAGE levels in serum and the
      severity of DR. METHODS: Circulating levels of sRAGE, sVCAM-1, and NO were
      examined in 37 type 2 diabetic patient and 20 age-matched healthy nondiabetic
      subjects using ELISA. The diabetic subjects were categorized as patients without
      retinopathy, patients with nonproliferative DR (NPDR), and patients with
      proliferative DR (PDR). RESULTS: Serum sRAGE levels were significantly lower in
      patients with NPDR and PDR than in healthy controls and in those without
      retinopathy (1331.13 +/- 126.13, 934.87 +/- 66.27 vs. 1712.69 +/- 167.3, 1833.1
      +/- 153.06 pg/ml, respectively, P<.05). Serum sVCAM-1 and NO were significantly
      higher in diabetic patients (1310.215 +/- 54.712 vs. 616.55 +/- 12.9 ng/ml and
      96.432 +/- 0.864 vs. 28.78 +/- 5.88 MUmol/l, respectively, P<.05) and were
      positively associated with the severity of DR. CONCLUSIONS: The results indicate
      that sRAGE is an endogenous protection factor against the occurrence of
      accelerated DR.

PMID- 20685138
TI  - Differential effects of trimethylamine and quinine on seizures induced by 4
      aminopyridine administration in the entorhinal cortex of vigilant rats.
AB  - In vivo and in vitro evidence from animals suggesting that gap junctions (GJs)
      play a role in the spreading of epileptiform activity. We have examined the
      influence of the gap junction opener trimethylamine (TMA) and the connexin 36
      (Cx36) gap junctional blocker, quinine, on epileptiform activity induced by 4
      aminopyridine (4-AP) in the rat entorhinal cortex (EC) and the CA1 hippocampal
      region. A cannula and surface electrodes were implanted into the brain to
      administer drugs and to monitor electrical activity. Injection of 4-AP (10 nmol)
      produced epileptiform discharge trains of high amplitude and frequency associated
      with seizure behavior rated between 0 and 3 in the Racine scale. In the presence
      of TMA (500 nmol), 4-AP produced distinct epileptiform patterns with continuous,
      long epileptiform discharges of high amplitude and frequency associated with
      seizure behavior of 0, 1, 3 and 5 during the first 30 min post-drug
      administration that diminished after 90 min. Quinine injection (35 pmol) into the
      EC of seizing animals decreased the amplitude and frequency of the discharge
      trains in the EC and CA1 regions, which were completely blocked after 34 min.
      Indeed, the seizure behavior of the animals was completely blocked in five of the
      six rats 53.2s after quinine administration. We suggest that the intensity of the
      proepileptic effect of TMA on epileptiform activity depends on the time and route
      of drug administration, and that neural Cx36-dependent GJs are important
      structures in the generation of epileptiform activity, as well as in the seizure
      behavior induced by 4-AP.

PMID- 20685139
TI  - Post genital mutilation giant clitoral epidermoid inclusion cyst in Benin City,
      Nigeria.
AB  - OBJECTIVE: To report overall occurrence, and the mode of presentation and
      management of girls with post genital mutilation giant clitoral epidermoid
      inclusion cyst in an African subregion. METHODS: This is a prospective experience
      with female patients who presented at two centers in Benin City, Nigeria, between
      January 2005 and December 2009 with clitoral epidermoid inclusion cyst following
      underground traditional female genital mutilation performed on neonates. RESULTS:
      In total, 37 patients were seen with clitoral epidermoid inclusion cyst, 15
      (40.5%) were post pubertal girls who could no longer cope with giant cyst that
      measured more than 3.5 * 6.5 cm in size at an average age of 17 (range 14-21)
      years. Ignorance, financial constraints, and the fear of possible prosecution by
      anti-female genital mutilation agencies were reasons for late presentation.
      Consequently, rapid increase in size of all cysts (100%), mass effect producing
      dragging discomfort in the vulva of 14 (93.3%) girls, social stigmatization of 12
      (80%) girls by peers and spouses, sexual difficulty experienced by 10 (66.7%),
      and irritating bulge in the perineum of 10 (66.7%) girls, were the most common
      indications for surgical consultation. Outcomes of cystectomy that included total
      clitoridectomy performed on on an outpatient basis mainly with local anesthesia
      were encouraging with no incidence of recurrence recorded on 1-4 years
      postoperative follow-up. CONCLUSION: Late presentation of girls with giant post
      genital mutilation clitoral epidermoid inclusion cysts was common. More campaigns
      against female genital mutilation and government policy aimed at encouraging
      patients with complications to seek early medical attention, and free treatment
      for those who present early are advocated.

PMID- 20685140
TI  - Equine influenza: a review of an unpredictable virus.
AB  - This review discusses some of the challenges still faced in the control of equine
      influenza virus H3N8 infection. A widespread outbreak of equine influenza in the
      United Kingdom during 2003 in vaccinated Thoroughbred racehorses challenged the
      current dogma on vaccine strain selection. Furthermore, several new developments
      in the first decade of the 21st century, including transmission to and
      establishment in dogs, a presumed influenza-associated encephalopathy in horses
      and an outbreak of equine influenza in Australia, serve as a reminder of the
      unpredictable nature of influenza viruses. The application of newly available
      techniques described in this review may further elucidate some of the viral
      factors that underlie recent events and provide the tools to better evaluate when
      vaccine strains should be updated.

PMID- 20685141
TI  - In vivo 13C spectroscopy in the rat brain using hyperpolarized [1-(13)C]pyruvate
      and [2-(13)C]pyruvate.
AB  - The low sensitivity of 13C spectroscopy can be enhanced using dynamic nuclear
      polarization. Detection of hyperpolarized [1-(13)C]pyruvate and its metabolic
      products has been reported in kidney, liver, and muscle. In this work, the
      feasibility of measuring 13C signals of hyperpolarized 13C metabolic products in
      the rat brain in vivo following the injection of hyperpolarized [1-(13)C]pyruvate
      and [2-(13)C]pyruvate is investigated. Injection of [2-(13)C]pyruvate led to the
      detection of [2-(13)C]lactate, but no other downstream metabolites such as TCA
      cycle intermediates were detected. Injection of [1-(13)C]pyruvate enabled the
      detection of both [1-(13)C]lactate and [13C]bicarbonate. A metabolic model was
      used to fit the hyperpolarized 13C time courses obtained during infusion of [1
      (13)C]pyruvate and to determine the values of VPDH and VLDH.

PMID- 20685142
TI  - An animal model of PDH deficiency using AAV8-siRNA vector-mediated knockdown of
      pyruvate dehydrogenase E1alpha.
AB  - We evaluated the feasibility of self-complementary adeno-associated virus (scAAV)
      vector-mediated knockdown of the pyruvate dehydrogenase complex using small
      interfering RNAs directed against the E1alpha subunit gene (PDHA1). AAV serotype
      8 was used to stereotaxically deliver scAAV8-si3-PDHA1-Enhanced Green Fluorescent
      Protein (knockdown) or scAAV8-EGFP (control) vectors into the right striatum and
      substantia nigra of rats. Rotational asymmetry was employed to quantify abnormal
      rotation following neurodegeneration in the nigrostriatal system. By 20weeks
      after surgery, the siRNA-injected rats exhibited higher contralateral rotation
      during the first 10min following amphetamine administration and lower 90-min
      total rotations (p<=0.05). Expression of PDC E1alpha, E1beta and E2 subunits in
      striatum was decreased (p<=0.05) in the siRNA-injected striatum after 14weeks. By
      week 25, both PDC activity and expression of E1alpha were lower (p<=0.05) in
      siRNA-injected striata compared to controls. E1alpha expression was associated
      with PDC activity (R(2)=0.48; p=0.006) and modestly associated with
      counterclockwise rotation (R(2)=0.51;p=0.07). The use of tyrosine-mutant scAAV8
      vectors resulted in ~17-fold increase in transduction efficiency of rat striatal
      neurons in vivo. We conclude that scAAV8-siRNA vector-mediated knockdown of PDC
      E1alpha in brain regions typically affected in humans with PDC deficiency results
      in a reproducible biochemical and clinical phenotype in rats that may be further
      enhanced with the use of tyrosine-mutant vectors.

PMID- 20685143
TI  - Prevalence and risk factors for feline obesity in a first opinion practice in
      Glasgow, Scotland.
AB  - A cross-sectional questionnaire study of cat owners registered with a first
      opinion veterinary practice was undertaken in July 2008. The body condition score
      (BCS) of the cats was assessed by the interviewer using a validated five point
      scale. Owners also rated their cat's BCS using five word descriptions. In total,
      118 questionnaires were collected. The prevalence of overweight or obese cats
      (BCS 4 or 5) was 39% (30.2-47.8%, n=61). Risk factors associated with overweight
      or obesity were frequency of feeding and neutered status. There was moderate
      agreement between owner and interviewer rating of BCS. Owner misperception was
      more likely when owners rated cats with BCS 1 (very thin) and 4 (overweight) and
      in longhaired cats. The study highlights the continuing need for owner education
      in feline nutrition and specifically the requirement for veterinarians to develop
      strategies to help owners correct their assessment of their cat's BCS.

PMID- 20685144
TI  - Assessment of the effectiveness and safety of natalizumab for treating relapsing
      remitting multiple sclerosis.
AB  - OBJECTIVE: Assessing the effectiveness and safety of natalizumab for treating
      relapsing-remitting multiple sclerosis in a tertiary hospital. METHOD:
      Observational, prospective study of adult patients treated with natalizumab from
      May 2007 until February 2009. TREATMENT: 300 mg natalizumab every four weeks.
      Response criteria: assessment of disease progression, appearance of flare-ups and
      assessment of magnetic resonance images. Adverse reactions during treatment with
      natalizumab were recorded. RESULTS: Thirty patients (73% female); average age 34
      +/- 8.4 years; mean baseline EDSS 3.4 +/- 1.3; number of flare-ups in the past
      year 2.1 +/- 1.2. TREATMENT was discontinued in five patients, due to refusal in
      one case, ineffectiveness in two cases and anaphylaxis in the other two cases.
      Fourteen patients completed one year of treatment with satisfactory results. A
      lower EDSS score by 36%, 47%, 31%, 54% and 28% was obtained at 3, 6, 9, 12 and 15
      months of treatment respectively. The prevalence of relapse-free patients was
      94%, 76% and 54% at 3, 6 and 12 months. MRI imaging studies in 11 patients one
      year after they began treatment showed no new lesions. Two patients suffered
      severe anaphylactic shock and another one had an outbreak of urticaria. The
      presence of neutralising antibodies was the reason for suspending treatment in
      6.6% of the patients. CONCLUSIONS: The treatment's effectiveness and safety in
      our patient group suggest that natalizumab is a treatment for refractory patients
      or those with aggressive types of multiple sclerosis, although we do not yet know
      about its long-term effects and the evolution of the appearance of neutralising
      antibodies.

PMID- 20685145
TI  - Circulating concentrations of alpha- and beta-chemokines in neonatal sepsis.
AB  - BACKGROUND: Despite advances in neonatal care, sepsis remains a threat, in
      particular for premature neonates, due to immature immunologic defense. Deficient
      chemotaxis, an essential process in the host response to pathogens, may
      contribute to this vulnerability. In this study we investigated chemokine
      expression in septic premature and term neonates. METHODS: Seventy-one neonates
      with signs and symptoms suggestive of systemic infection, requiring full sepsis
      evaluation and treatment, formed the study group; 58 neonates without sepsis
      served as the control group. Serum concentrations of two alpha-chemokines (GRO
      alpha and ENA-78) and two beta-chemokines (RANTES and MIP-1alpha) were measured
      at day 0 and day 3-5 of infection in the study group, and on the day of inclusion
      in the study in the control group. RESULTS: During infection, serum levels of GRO
      alpha in the study group were higher and serum levels of RANTES were lower as
      compared to those of the control group (p<0.001 and p<0.001, respectively).
      Furthermore, levels of GRO-alpha were higher and levels of RANTES were lower on
      day 0 as compared to levels on day 3-5 (p<0.001 and p<0.001, respectively).
      Chemokine serum concentrations on day 3-5 in the study group did not differ
      significantly as compared to those of the control group. Term and preterm infants
      seemed to respond similarly regarding chemokine expression. No significant
      differences were found in serum levels of MIP-1alpha and ENA-78. CONCLUSIONS: Our
      findings suggest up-regulation of GRO-alpha and down-regulation of RANTES at the
      onset of a septic episode, similar to the response pattern observed in septic
      adults. Both term and preterm neonates appear to have the potential to elicit a
      chemotactic response to infection.

PMID- 20685146
TI  - A transcriptome-based examination of blood group expression.
AB  - Over the last two decades, red cell biologists witnessed a vast expansion of
      genetic-based information pertaining to blood group antigens and their carrier
      molecules. Genetic progress has led to a better comprehension of the associated
      antigens. To assist with studies concerning the integrated regulation and
      function of blood groups, transcript levels for each of the 36 associated genes
      were studied. Profiles using mRNA from directly sampled reticulocytes and
      cultured primary erythroblasts are summarized in this report. Transcriptome
      profiles suggest a highly regulated pattern of blood group gene expression during
      erythroid differentiation and ontogeny. Approximately one-third of the blood
      group carrier genes are transcribed in an erythroid-specific fashion. Low-level
      and indistinct expression was noted for most of the carbohydrate-associated
      genes. Methods are now being developed to further explore and manipulate
      expression of the blood group genes at all stages of human erythropoiesis.

PMID- 20685147
TI  - Variability and stability analysis of walking of transfemoral amputees.
AB  - Variability and stability of walking of eight transfemoral amputees and eight
      healthy controls was studied under four conditions: walking inside on a smooth
      terrain, walking while performing a dual-task and walking outside on (ir)regular
      surfaces. Trunk accelerations were recorded with a tri-axial accelerometer.
      Walking speed, mean and coefficient of variation of stride times (ST) and the
      root mean squares (RMS) of trunk accelerations was calculated. Gait variability
      and stability were quantified using measures derived from the theory of
      stochastic dynamics. Regularity was indexed using the sample entropy (SEn) and
      the scaling exponent alpha derived form Detrended Fluctuations Analysis. Local
      stability (LSE) quantified gait stability. Walking speed was lower, but ST
      variability was not different for amputees than controls. RMS of medio-lateral
      accelerations was higher for amputees; SEn was higher, implying less predictable
      accelerations, and LSE higher, indicating decreased stability. The largest
      condition effect was present for walking outside: trunk RMS increased and LSE
      decreased. Differences in walking between amputees and healthy controls and their
      responses to perturbations revealed themselves in the magnitude, variability and
      stability measures of trunk accelerations. These results imply that quantifying
      the dynamical structure of trunk accelerations can differentiate between groups
      with different walking abilities and between conditions of increasing difficulty
      and may therefore provide a useful diagnostic tool.

PMID- 20685148
TI  - Validation of a dystonia screening questionnaire: testing in a cohort of mixed
      neurological disorders.

PMID- 20685149
TI  - Hyperventilation-induced painful tonic spasms secondary to a structural lesion of
      the pons.

PMID- 20685150
TI  - Diagnostic utility of clinical tests for spinal dysfunction.
AB  - The purpose of this study was to outline the clinical tests that exhibit the
      highest diagnostic utility for the spine. Using a sensitive search strategy but
      highly restrictive inclusion criteria based on assessment of quality and
      reduction of bias, we identified 16 well constructed diagnostic accuracy studies
      of the spine. Within the 16 studies, 14 clinical tests were identified, and of
      the 14, four cervical tests and two lumbar tests were considered good screening
      tools whereas one cervical test and five lumbar tests were considered good tools
      for confirmatory diagnosis. A significant number of clinical tests were not
      included in our final tally secondary to poor study designs and the risks
      associated with inflated findings and bias. High quality diagnostic accuracy
      studies for the spine are necessary to improve clinicians' abilities to rule out
      sinister disorders.

PMID- 20685152
TI  - Does a cognate receptor know its own effector?

PMID- 20685153
TI  - Multiple q-shell diffusion propagator imaging.
AB  - Many recent high angular resolution diffusion imaging (HARDI) reconstruction
      techniques have been introduced to infer an orientation distribution function
      (ODF) of the underlying tissue structure. These methods are more often based on a
      single-shell (one b-value) acquisition and can only recover angular structure
      information contained in the ensemble average propagator (EAP) describing the
      three-dimensional (3D) average diffusion process of water molecules. The EAP can
      thus provide richer information about complex tissue microstructure properties
      than the ODF by also considering the radial part of the diffusion signal. In this
      paper, we present a novel technique for analytical EAP reconstruction from
      multiple q-shell acquisitions. The solution is based on a Laplace equation by
      part estimation between the diffusion signal for each shell acquisition. This
      simplifies greatly the Fourier integral relating diffusion signal and EAP, which
      leads to an analytical, linear and compact EAP reconstruction. An important part
      of the paper is dedicated to validate the diffusion signal estimation and EAP
      reconstruction on real datasets from ex vivo phantoms. We also illustrate
      multiple q-shell diffusion propagator imaging (mq-DPI) on a real in vivo human
      brain and perform a qualitative comparison against state-of-the-art diffusion
      spectrum imaging (DSI) on the same subject. mq-DPI is shown to reconstruct robust
      EAP from only several different b-value shells and less diffusion measurements
      than DSI. This opens interesting perspectives for new q-space sampling schemes
      and tissue microstructure investigation.

PMID- 20685151
TI  - NF-kappaB inducing kinase: a key regulator in the immune system and in cancer.
AB  - NF-kappaB inducing kinase (NIK) is a kinase that activates the canonical and non
      canonical NF-kappaB pathways to control transcriptional expression of certain
      proteins such as cytokines, chemokines and NF-kappaB signaling molecules. Many
      advances have been made in understanding the molecular mechanisms by which the
      stability of NIK is regulated to affect downstream signaling. Genetic mouse
      models suggest that NIK plays an essential role in the regulation of the immune
      system as well as in the bone microenvironment. Increasing evidence links NIK to
      the tumorigenesis of hematological cancers, such as multiple myeloma, and solid
      tumors, such as pancreatic carcinoma and melanoma. Understanding the mechanism by
      which NIK is de-regulated will potentially provide therapeutic options for
      certain diseases such as autoimmunity and cancer.

PMID- 20685154
TI  - Reputation management in the age of the world-wide web.
AB  - The reciprocal interactions with others that play such a significant part in our
      lives depend upon trust; individuals need to be confident that their partners are
      cooperative, and that they will return favours. Reputation permits the choice of
      better partners and provides incentives to be more cooperative. These uses of
      reputation are not unique to humans. However, in complex human societies, with
      large numbers of potential partners, keeping track of each other's reputation is
      a vital part of everyday life, and, in an inevitable arms race, ever more
      powerful strategies of reputation management are being developed. In this
      article, we bring together insights from different disciplines to throw new light
      onto the importance and scope of reputation management.

PMID- 20685155
TI  - Clever animals and killjoy explanations in comparative psychology.
AB  - From the process of organic evolution to the analysis of insect societies as self
      organizing systems, biology is full of awe-inspiring examples of complexity
      arising from simplicity. Yet in the contemporary study of animal cognition,
      demonstrations that complex human-like behavior arises from simple mechanisms
      rather than from 'higher' processes, such as insight or theory of mind, are often
      seen as uninteresting and 'killjoy', almost a denial of mental continuity between
      other species and humans. At the same time, however, research elsewhere in
      psychology increasingly reveals an unexpected role in human behavior for simple,
      unconscious and sometimes irrational processes shared by other animals. Greater
      appreciation of such mechanisms in nonhuman species would contribute to a deeper,
      more truly comparative psychology.

PMID- 20685156
TI  - Molecularly imprinted polymer sensor arrays.
AB  - The sensor array format has proved an effective method of transforming sensors of
      modest selectivity into highly selective and discriminating sensors. The primary
      challenge in developing new sensor arrays is collecting together a sufficient
      number of recognition elements that possess different binding affinities for the
      analytes of interest. In this regard, the use of molecularly imprinted polymers
      (MIPs) as the recognition elements in sensor arrays has a number of unique
      advantages. MIPs can be rapidly and inexpensively prepared with different
      selectivities and tuned with different selectivity patterns via the choice of
      templates in the imprinting process. The array format also helps compensate for
      the low selectivities and high cross-reactivities of MIP sensors. These
      attractive qualities of MIP sensor arrays have been demonstrated in recent
      examples, which have established the viability and generality of the approach. In
      particular, the versatility of the imprinting process enables MIP sensor arrays
      to be tailored to specific analytes. MIP sensor arrays have also shown
      surprisingly broad utility, as even analytes that were not used as templates in
      the imprinting process can be effectively discriminated.

PMID- 20685157
TI  - Properties of the Michael's adducts of the substituted 2-amino-5-oxonitriles.
AB  - A series of five substituted 2-amino-5-oxonitriles, obtained by the Michael
      reaction have been designed, synthesised, isolated and spectroscopically and
      structurally elucidated by means of single crystal X-ray diffraction, linear
      polarized infrared (IR-LD) and UV-spectroscopy, (1)H NMR, mass spectrometry and
      thermal methods. Theoretical quantum chemical calculations were carried out, thus
      supporting the experimental optical properties and electronic structure of
      compounds studied.

PMID- 20685158
TI  - Cautionary note: linewidth effect in dynamic NMR.
AB  - In using NMR spectroscopy to evaluate the effects of kinetic processes taking
      place in the solute molecules being studied, one must estimate the inherent width
      w of each line, which is hidden from view throughout the kinetic thermal region
      due to the line-width broadening effected by the processes. We have herein built
      a self-consistent model function w(T) to attempt to evaluate the variation in the
      Arrhenius activation energy obtained with the model parameters present in w(T).
      As it turns out, a sizable number of such line-width parameters yields excellent
      spectral fits, and these lead to a considerable range of possible activation
      energies.

PMID- 20685159
TI  - Comparing the working time between Bar-Code Medication Administration system and
      traditional medication administration system: an observational study.
AB  - BACKGROUND: The medical institutions had paid attention to the medication error
      via Bar-Code Medication Administration system (BCMA) to improve the accuracy of
      the medication process for patient safety. Yet, the working time of drug delivery
      was under investigated. OBJECTIVES: Comparing the working time of oral drugs
      between Bar-Code Medication Administration system and traditional medication
      administration system. METHODS: Purposive sampling, observational and
      questionnaire study design was used. Participants were invited from a medical
      center in North Taiwan, 51 nurses from three neurosurgical wards who were using
      the BCMA system; 51 nurses from three neurological wards who were using
      traditional medication administration record (MAR). The working time of oral
      medication administration including order transcribing, verifying, drug giving,
      and renew in BCMA and traditional group were observed and recorded. RESULTS: (1)
      Working time for oral medication administration reduced from 36.49 to 18.42 s
      after BCMA implementation. (2) In the same period, working times for oral drug
      administration were 62.89 and 56.07 s before and after BCMA implementation in the
      traditional group. (3) Most nurses (66.7%) felt BCMA could save their oral drug
      administration time under 50%. (4) Frequent crash of the wireless network, which
      extended the oral drug administration time was the major threat in the process of
      BCMA implementation. (5) 93.5% nurses think that BCMA could enhance patient oral
      medication safety and promote quality of oral medication. CONCLUSIONS: The
      results demonstrated that implementation of BCMA for oral medication could reduce
      half of the time for oral medication delivery. Nurses coordinated the hardware
      and software by accommodating the new facilities and operating BCMA system. The
      stability of wireless Internet was the main threat. However, 93.5% nurses think
      that BCMA could enhance patient oral medication safety in spite of making more
      effort in learning new technology.

PMID- 20685160
TI  - Single cytomegalovirus strain associated with fetal loss and then congenital
      infection of a subsequent child born to the same mother.
AB  - BACKGROUND: Intrauterine transmission of cytomegalovirus (CMV) can occur even in
      CMV-seropositive mothers. Previous studies demonstrated re-infection with a newly
      acquired CMV strain during pregnancy had a major role in such transmission.
      Although reactivation of latently infected CMV is another plausible cause, no
      direct evidence has been documented. OBJECTIVES: We sought to identify the
      route(s) and maternal risk factor of CMV infection that occurred in consecutive
      pregnancies and resulted in symptomatic congenital infections. STUDY DESIGN: A
      newborn identified with congenital CMV infection in our newborn screening program
      developed hearing loss and subsequent nystagmus. The mother had a history of an
      elective abortion due to a severe fetal CMV infection 32 months prior to delivery
      of this newborn. We analyzed maternal serological changes and compared CMV
      genomic sequences in specimens obtained from the aborted fetus and the present
      case. We also analyzed immunological functions of the mother. RESULTS: Our major
      findings were as follows: (1) the aborted fetus and the present case were
      infected with the same strain. (2) The congenital infection that resulted in the
      abortion was due to a primary infection. (3) CMV DNA was undetectable in the
      mother's blood from 3 months after the abortion. These results strongly suggested
      that maternal viral reactivation caused the congenital infection in the present
      case. However, we could not find impairment of immunological functions in the
      mother. CONCLUSIONS: Viral reactivation in an apparently immunocompetent mother
      can cause symptomatic congenital CMV infection.

PMID- 20685161
TI  - Maturation of auditory evoked potentials from 6 to 48 months: prediction to 3 and
      4 year language and cognitive abilities.
AB  - OBJECTIVE: To investigate the maturation of long-latency auditory evoked
      potentials (LLAEP) from 6 to 48 months in infants with a family history of
      language impairment (FH+) and control infants (FH-). METHODS: LLAEPs of seventeen
      FH+ infants were compared to 28 FH- infants at 6, 9, 12, 16, 24, 36 and 48
      months. Participants received a passive oddball paradigm using fast- and slow
      rate non-linguistic auditory stimuli and at 36 and 48 months completed a battery
      of standardized language and cognitive tests. RESULTS: Overall, the morphology of
      LLAEP responses differed for fast- versus slow-rate stimuli. Significant age
      related changes in latency and amplitude were observed. Group differences,
      favoring FH- infants, in the rate of maturation of LLAEPs were found. Responses
      to fast-rate stimuli predicted language abilities at 36 and 48 months of age.
      CONCLUSIONS: The development of LLAEP in FH+ children is modulated by differences
      in the rate of maturation as well as variations in temporal processing abilities.
      SIGNIFICANCE: These findings provide evidence for the role of non-linguistic
      auditory processes in early language development and illustrate the utility of
      using a perceptual-processing skills model to further our understanding of the
      precursors of language development and impairment.

PMID- 20685162
TI  - Simple metabolite extraction method for metabolic profiling of the solid-state
      fermentation of Aspergillus oryzae.
AB  - Solid-state culture of microorganisms is an important style of culture both in
      the traditional food industry and in the modern fermentation industry. We propose
      here a simple method for metabolite extraction from the solid-state fermentation
      of a filamentous fungus, Aspergillus oryzae, which is known as rice-koji. To
      evaluate the efficiency of metabolite extraction, liquid chromatography-mass
      spectrometry (LC/MS) was used for simultaneous detection of a wide range of
      metabolites including amino acids, organic acids and vitamins, which are of
      interest in rice-koji making. Among eleven different metabolite extraction
      methods tested, we found that extraction using acetonitrile/water (50:50),
      coupled with boiling at 70  degrees C for 5 min, was advantageous in terms of
      both extraction yield and metabolism quenching. We consider that our method
      provides a technical basis for metabolome analysis of a solid-state fermentation.

PMID- 20685163
TI  - Polysomnogram changes in marijuana users who report sleep disturbances during
      prior abstinence.
AB  - BACKGROUND: Abrupt discontinuation of heavy marijuana (MJ) use is associated with
      self-reports of sleep difficulty. Disturbed sleep is clinically important because
      MJ users experiencing sleep problems may relapse to MJ use to improve their sleep
      quality. Few studies have used polysomnography (PSG) to characterize changes in
      sleep architecture during abrupt abstinence from heavy MJ use. METHODS: We
      recorded PSG measures on nights 1, 2, 7, 8, and 13 after abrupt MJ
      discontinuation in 18 heavy MJ users residing in an inpatient unit. RESULTS:
      Across abstinence, Total Sleep Time (TST), Sleep Efficiency (SEff), and amount of
      REM sleep declined, while Wake after Sleep Onset (WASO) and Periodic Limb
      Movements (PLM) increased. Furthermore, quantity (joints/week) and duration
      (years) of MJ use were positively associated with more PLMs. CONCLUSION: The
      treatment of sleep disturbance is a potential target for the management of
      cannabis use disorders since poor sleep could contribute to treatment failure in
      heavy MJ users.

PMID- 20685164
TI  - Immediate versus delayed self-reporting of symptoms and side effects during
      chemotherapy: does timing matter?
AB  - PURPOSE: The aim of this study was to examine how patients recall symptoms at a
      delayed self-report. Accurate insight into toxicity symptoms during chemotherapy
      is essential so that nurses and doctors can assess therapeutic tolerance and
      adjust supportive care accordingly. METHOD: A non-experimental, longitudinal
      design was employed. Using the Therapy-Related Symptoms Checklist (TRSC),
      respondents (n = 142) reported their initial symptoms during the first 7 days of
      the chemotherapy cycle at two different times: (1) each day of the first seven
      days after the chemotherapy administration (immediate self-report), and (2) at
      their next hospital visit for chemotherapy (delayed self-report). We compared the
      number and severity of symptoms and side effects reported in the immediate and
      delayed self-reports. RESULTS: Respondents reported significantly fewer symptoms
      and fewer severe symptoms in the delayed self-report. For 22 out of 25 symptoms
      the delayed-reported grade was significantly lower than the immediate-reported
      maximum grade. Compared to the immediate-reported median grade, significant
      differences occurred in only 10 out of the 25 symptoms. In all cases, except
      fatigue, the delayed-reported grade was significantly higher than the immediate
      reported median grade. CONCLUSIONS: This study indicates that delayed self-report
      of chemotherapy side effects is not an appropriate measure of actual symptoms and
      side effects experienced by patients. Delayed self-report gives a weaker insight
      into actual symptom burden. Fatigue is at particular risk to be minimized at the
      delayed self-report. Therefore it is recommended to assess chemotherapy-related
      symptoms and side effects by means of immediate self-report.

PMID- 20685165
TI  - Therapeutic applications of ribozymes and riboswitches.
AB  - Therapeutic approaches employing RNA as a tool or as a drug target have recently
      emerged and have been employed for various applications-ranging from cancer
      treatment to virus infection. Despite the paucity of its molecular groups
      compared to proteins, RNA has nevertheless proved to be an excellent choice for
      researchers who have aspired to develop therapeutic tools. Ribozymes and
      riboswitches are RNA-based therapeutic tools that are most often employed to
      knockdown gene expression and to inhibit bacterial infections, respectively. The
      aim of this review is to summarize recent advances observed in ribozyme- and
      riboswitch-based therapeutic applications that, in some cases, have reached
      clinical trials.

PMID- 20685166
TI  - Pre-transplant manipulation processing of umbilical cord blood units: Efficacy of
      Rubinstein's thawing technique used in 40 transplantation procedures.
AB  - BACKGROUND: Umbilical cord blood (UCB) is a valid alternative to be used in
      transplanted patients. Limitations of the use of stem cells depends on the small
      number of cells available; this is the reason why UCB can be used only in very
      low-weight patients. In this study we have evaluated the efficacy of cellular
      manipulation before transplant and in particular, before thawing the units
      through the Rubinstein method. METHODS: We have evaluated the results obtained
      after thawing 40 UCB to be used for as many patients affected by several
      pathologies (21 ALL, 6 AML, 3 MDS, 2 LNH, 2 histiocytosis, 2 beta-thalassemia, 1
      Chediak-Higashi syndrome, 1 Fanconi anemia, 1 Wiskott-Aldrich syndrome and 1
      Omenn syndrome). RESULTS: After thawing, nucleated cells (NC) mean recovery was
      76.81% (SD+/-15.41). The quantity of NC obtained was 124.29*107 (SD+/-43.18) and
      in only 5 cases the number of NC after the procedure was lower than the requested
      graft dose. Among the last ones, in two cases only we did not achieve the target
      after manipulation. The post-manipulation cellular viability was 83.48% (SD+/
      10.6). For all the units shipment complied with all the necessary procedures; in
      fact the temperature never rose above -120 degrees C. CONCLUSION: In our study we
      highlighted the efficacy of UCB thawing technique, with the same method defined
      in 1995 at the New York Blood Centre that guarantees an excellent NC recovery and
      maintains a high level of cell viability.

PMID- 20685167
TI  - Training courses for pediatric apheresis on site; how apheresis technology
      transfer can be performed.
AB  - Apheresis technology for pediatric patients and donors is still cumbersome, it is
      rare, mostly done in departments specialized for apheresis in adult patients, and
      therefore the staff is more or less anxious about dealing with especially little
      pediatric patients or donors. Our center is specialized in pediatrics and has a
      department for apheresis. We offered training courses for interested centers,
      which want to use the AMICUSTM system for leukapheresis in small children. In a 1
      2 ay course the principles of leukapheresis in very small children were trained.
      To investigate the reproducibility of this training courses we invited the
      centers to share their data with us. As a standard we used a formula
      (C=[(AD):B*0.5]:1000) for predicting the CD34+ cell yield (C) by calculating the
      yield from total blood volume (D) processed, bodyweight (B), CD34+ cell count in
      peripheral blood (A) and an assumption of the collection efficiency of 50% (0.5).
      We hypostasized that the deviation of different centers should be in comparable
      limits of agreement as our own data. Thirteen centers from Germany, Poland,
      Ukraine, Romania, Italy, Hungary, and Slovakia asked from 1999 until today for
      support for pediatric leukapheresis. 6 centers sent 20 case report forms back (9
      blood priming, 6 saline priming), from which 15 were completely filled in and
      available for the evaluation. The data were compared to 129 leukapheresis (41
      blood priming, 88 saline priming) performed in our institution. The limit of
      agreement to the formula was -17.6% (+/-43) compared to -10.5% (+/-36). There was
      no statistically differences by the Mann-Whitney-U-test (p=0.5607). We conclude
      that training course held on site in different centers in different country could
      led to reproducible performance of standardized leukapheresis procedures in small
      children. In the future this could be a way for quality control in pediatric
      apheresis.

PMID- 20685168
TI  - Music interventions in patients during coronary angiographic procedures: a
      randomized controlled study of the effect on patients' anxiety and well-being.
AB  - BACKGROUND: A cardiac catheterization laboratory can be a frightening environment
      and music can be a supportive source of environmental sound that stimulates and
      maintains relaxation. AIM: To test the effects of patient focused music versus
      loudspeaker music versus standard sound on patient's experiences of anxiety and
      well-being during coronary angiographic procedures. METHODS: A prospective,
      randomized, controlled trial of 98 subjects undergoing elective coronary
      angiogram and/or percutaneous coronary intervention. The subjects were randomly
      allocated to three different groups of sound environments: a control group (the
      usual sound environment), a patient focused music group (audio pillow) or to a
      loudspeaker music group. RESULTS: Anxiety decreased significantly and well-being
      increased significantly in the two music groups compared to the control group.
      There was a significantly more positive impression of the sound environment in
      the patient focused music group compared to the two other groups. CONCLUSION:
      This study showed that the use of a specially designed music reduced anxiety and
      increased well-being in patients during coronary angiographic procedures.
      However, patient focused music seemed to be more preferable. The sound
      environment was rated more positively by the subjects listening to music via
      audio pillow. The music delivered via loudspeakers seemed to distract the staff
      during the examination at the cardiac catheterization laboratory.

PMID- 20685169
TI  - Training, education and assessment. Preface.

PMID- 20685170
TI  - New undergraduate curricula in the UK and Australia.
AB  - There are many challenges facing undergraduate education in the smaller
      specialities such as obstetrics and gynaecology (O&G). These are similar
      throughout the world, although the emphasis may vary according to geography and
      the approach of those involved in medical education in general. The number of
      medical students has increased because of the greater number of doctors required,
      the gender balance and also because it provides revenue for the universities.
      This means that strategies must be developed to include more teaching units in
      both primary and secondary care as well as those at a distance from the main
      teaching provider. Australia and the UK both have this problem but, obviously,
      the distances involved in Australia are much greater. One of the drivers for the
      change in undergraduate medical education in the UK was factual overload and the
      need to teach basic competencies to the students. National curricula that take
      this into account are being developed and that in the UK has been taken up by a
      majority of the medical schools. The opportunities offered by O&G to provide
      basic skills and competencies difficult to find elsewhere in the curriculum are
      unparalleled. These include issues such as communication in situations where
      great sensitivity is required and also the impact of cultural beliefs and
      ethnicity on clinical practice. However, factual knowledge of medical science is
      also essential and ways of achieving a balance are discussed.

PMID- 20685171
TI  - Laser-evoked potentials habituation in fibromyalgia.
AB  - Abnormalities of central pain processing play an important role in the
      pathophysiology of fibromyalgia (FM). The aims of the present study were to: 1)
      evaluate habituation of laser-evoked potentials (LEP) to repeated painful
      stimulation of 1 tender and 2 nontender points; and 2) determine correlations
      between LEP abnormalities and major clinical features of FM. Fourteen consecutive
      FM outpatients and 13 normal controls were included. LEP were recorded from scalp
      designations Fz, Cz, Pz, T3, and T4. The dorsum of the right hand, the right
      supra-orbital zone, and the right knee (a tender point in all patients) were
      subjected to repeated CO2 laser stimuli. For each stimulation site, recordings
      were obtained for 3 consecutive series of 20 stimuli. The 3 main findings in FM
      patients were: 1) an increased amplitude of vertex LEP and subjective laser pain;
      2) decreased habituation of vertex LEP and subjective laser pain; and 3) a
      correlation between reduced N2 wave habituation and the severity of self-reported
      depressive symptoms. As with other chronic pain syndromes, the pathophysiology of
      FM may involve a generalized increase in the perception of painful stimuli and
      reduced habituation of the sensory cortex. PERSPECTIVE: Reduced habituation of
      cortical responses to laser stimuli in FM patients suggests alterations in the
      pattern of cortical excitability. This is facilitated by depressive symptoms and
      abnormalities in central neurotransmission. These findings provide further
      support for the use of medications with effects on the central nervous system in
      the management of FM.

PMID- 20685172
TI  - Varying perceived social threat modulates pain behavior in male mice.
AB  - We previously demonstrated that male mice display significantly reduced pain
      behavior on the acetic acid abdominal constriction test when confined in close
      proximity to a stranger male mouse. We show here the testosterone-dependence (via
      castration and testosterone propionate replacement) of this phenomenon, likely a
      form of (social) stress-induced analgesia. However, when similar male dyads are
      separated by vertical metal bars, allowing only partial physical contact, we find
      that the mice exhibit hyperalgesia, not analgesia, in response to both acetic
      acid injection and noxious radiant heat, relative to testing in isolation. This
      finding is specific to same-sex male dyads, and no change in nociceptive
      sensitivity is observed when males are tested in the presence of a female
      conspecific. We propose that pain sensitivity varies with respect to the severity
      of the social threat: mild social threat produces hyperalgesia and more severe
      social threat produces analgesia. PERSPECTIVE: This work highlights the
      importance of social threat in modulating pain behavior in a sex-specific manner.
      The findings add to a growing body of evidence that social factors affect pain
      behavior in mice, thus allowing the study of the mechanistic underpinnings of
      social modulation of pain in humans.

PMID- 20685173
TI  - Subacute penile numbness after brachytherapy for prostate cancer.
AB  - PURPOSE: Penile numbness is a rare complication of permanent prostate
      brachytherapy, and optimal clinical management remains unclear. We present such a
      case and discuss pathophysiology and clinical management strategies. METHODS AND
      MATERIALS: A 68-year-old male presented with a serum prostate-specific antigen
      level of 6.9 ng/mL, Gleason score of 7 (3+4), and clinical T1c adenocarcinoma of
      the prostate. After a permanent prostate brachytherapy implant with (125)I
      monotherapy to a dose of 145Gy, the patient developed complete penile numbness
      postoperatively on the third day. RESULTS: The patient experienced complete
      restoration of penile sensation and function by postoperative day 9 with
      conservative management. CONCLUSIONS: Subacute penile shaft numbness after
      brachytherapy is rare and is caused by dorsal penile nerve compression. Over the
      course of a week, the restoration of penile sensation is likely to occur with
      conservative management.

PMID- 20685174
TI  - Comparison of conservative management techniques in the re-treatment of
      ipsilateral breast tumor recurrence.
AB  - PURPOSE: To compare brachytherapy and three-dimensional (3-D) conformal external
      beam radiotherapy for breast cancer presenting in the previously irradiated
      breast. METHODS AND MATERIALS: Thirty-six patients with TIS-T2 breast carcinomas
      received brachytherapy or 3-D conformal radiotherapy (3-D CRT) after lumpectomy
      in a previously irradiated breast as an alternative to salvage mastectomy.
      Brachytherapy consisted of low-dose-rate (LDR) interstitial technique in 21
      patients, whereas 11 patients were treated using high-dose-rate (HDR) balloon
      technique. Four patients received 3-D CRT. Cosmesis was graded according to the
      Harvard criteria and the Allegheny General Modification of the Harvard criteria.
      Acute sequelae were graded according to the Common Terminology Criteria for
      Adverse Events (version 3.0). RESULTS: Thirty-five of 36 patients remained free
      of local failure, with a mean followup of 37 months. Five patients treated with
      LDR developed Grade II and two developed Grade III acute side effects. No patient
      treated with balloon brachytherapy or 3-D CRT developed a Grade II or higher
      acute effect. Cosmetically, 12 LDR interstitial patients were scored as Grade I,
      six as Grade II, and three as Grade III. Nine of the HDR patients were scored as
      Grade I, one as Grade II, and one as Grade III. Two 3-D CRT patients were scored
      as Grade II and two as Grade III. The Allegheny Modification of the Harvard
      criteria more accurately reflected the cosmetic effects of re-treatment.
      CONCLUSION: Brachytherapy is feasible for patients who desire breast preservation
      in a previously irradiated breast. All techniques demonstrated similar local
      control rates. Acute side effects were less, and cosmesis was superior in HDR
      balloon brachytherapy.

PMID- 20685175
TI  - Effects of ellipsoid prostate deformation on dose delivery during permanent
      interstitial brachytherapy.
AB  - PURPOSE: To elucidate the potential effects of prostate deformation on dose
      distribution during Iodine-125 ((125)I) seed implantation brachytherapy for
      prostate cancer. METHODS AND MATERIALS: A retrospective analysis of 245 patients
      who underwent only transperineal brachytherapy for low-risk prostate
      adenocarcinoma was performed. The maximum diameters of the prostate were measured
      before treatment by transrectal ultrasound volumetry along right to left (RL),
      anterior to posterior (AP), and apex to base (Length) directions. The seeds were
      inserted by the modified peripheral loading method using real-time ultrasound
      guided seed placement. The ellipsoid deformation rates in the axial plane (E(ax))
      and in the sagittal plane (E(sag)) were defined as [RL-AP]/RL and [Length
      AP]/Length, respectively. The correlation between them and the dose-volume
      histogram parameters at 30 days after the operation was evaluated. A simulation
      test was additionally performed to ascertain the change in dose distribution
      among virtual volumes built in a radiotherapy planning device that corresponds to
      prostates with increased Eax or Esag. RESULTS: The mean Esag and Eax of patients
      were 0.313 (range, -0.28 to 0.844) and 0.261 (range, -0.02 to 0.54),
      respectively. Esag showed a positive correlation with dose (Gy) covering 90% of
      the prostate volume (pD(90)), prostate volume (%) covered by 100% of the
      prescribed dose (pV(100)), the rectal volume (cc) irradiated by 100% of the
      prescribed dose (rV(100)), and the rectal volume (cc) irradiated by 150% of the
      prescribed dose (rV(150)), whereas Eax showed a positive correlation with
      prostate volume (%) covered by 150% of the prescribed dose (pV(150)) and the
      urethral dose (Gy) delivered to 5% of its volume (uD(5)). The simulation test
      suggested that the prescribed dose resulted in the best coverage in patients with
      increased E(sag), and that patients with increased E(ax) exhibited poor urethral
      sparing from overdosage. CONCLUSION: In the seed implantation method, ellipsoid
      deformation of the prostate causes higher rectal dose exposure or dose delivery
      to the urethra.

PMID- 20685176
TI  - Comparison of PSA relapse-free survival in patients treated with ultra-high-dose
      IMRT versus combination HDR brachytherapy and IMRT.
AB  - PURPOSE: We report on a retrospective comparison of biochemical outcomes using an
      ultra-high dose of conventionally fractionated intensity-modulated radiation
      therapy (IMRT) vs. a lower dose of IMRT combined with high-dose-rate (HDR)
      brachytherapy to increase the biologically effective dose of IMRT. METHODS:
      Patients received IMRT of 86.4Gy (n=470) or HDR brachytherapy (21Gy in three
      fractions) followed by IMRT of 50.4Gy (n=160). Prostate-specific antigen (PSA)
      relapse was defined as PSA nadir+2. Median followup was 53 months for IMRT alone
      and 47 months for HDR. RESULTS: The 5-year actuarial PSA relapse-free survival
      (PRFS) for HDR plus IMRT vs. ultra-high-dose IMRT were 100% vs. 98%, 98% vs. 84%,
      and 93% vs. 71%, for National Comprehensive Cancer Network low- (p=0.71),
      intermediate- (p<0.001), and high-risk (p=0.23) groups, respectively. Treatment
      (p=0.0006), T stage (p<0.0001), Gleason score (p<0.0001), pretreatment PSA
      (p=0.0037), risk group (p<0.0001), and lack of androgen-deprivation therapy
      (p=0.0005) were significantly associated with improved PRFS on univariate
      analysis. HDR plus IMRT vs. ultra-high-dose IMRT (p=0.0012, hazard ratio
      [HR]=0.184); age (p=0.0222, HR=0.965); and risk group (p<0.0001, HR=2.683) were
      associated with improved PRFS on multivariate analysis. CONCLUSION: Dose
      escalation of IMRT by adding HDR brachytherapy provided improved PRFS in the
      treatment of prostate cancer compared with ultra-high-dose IMRT, independent of
      risk group on multivariate analysis, with the most significant benefit for
      intermediate-risk patients.

PMID- 20685177
TI  - Intra-articular chromic phosphate (32P) in the treatment of diffuse pigmented
      villonodular synovitis.
AB  - PURPOSE: Pigmented villonodular synovitis (PVNS) is an uncommon proliferative
      lesion of synovial tissue. In diffuse PVNS, recurrence rates are high after
      resection alone. Adjuvant external beam radiation therapy contributes to improved
      local control. Limited data exist for intra-articular radioisotope therapy after
      surgical resection. We report institutional experience with intra-articular
      chromic phosphate ((32)P). METHODS AND MATERIALS: Records were reviewed from the
      Department of Radiation Oncology at Indiana University. Nine cases of PVNS
      treated with (32)P were identified (mean age=40). Seven patients were treated at
      time of recurrence and 2 patients were treated prophylactically. Intra-articular
      injections were performed by accessing the joint space, aspirating joint fluid,
      reinjecting 1-2 mCi of (32)P, and barbitaging to ensure good distribution in the
      joint space. No external beam radiation therapy was delivered. One patient was
      lost to followup. Mean followup of remaining patients was 20 months (range, 2
      48). RESULTS: Eleven injections were performed in 9 patients. Eight had PVNS in
      the knee(s) and 1 patient had involvement of the hip. Two patients were treated
      more than once, one for a recurrence in the same joint at 13 months and another
      for PVNS of a contralateral joint. Three clinical recurrences (2, 13, and 28
      months) were noted. Two of three recurrences were in patients who had bulky
      diffuse PVNS at the time of injection. Overall local control was 70%. In patients
      without bulky diffuse PVNS at the time of injection, local control was 88%.
      CONCLUSION: We report success using intra-articular injections of (32)P after
      synovectomy in patients with PVNS.

PMID- 20685178
TI  - Second conservative treatment for ipsilateral breast cancer recurrence using high
      dose rate interstitial brachytherapy: preliminary clinical results and evaluation
      of patient satisfaction.
AB  - PURPOSE: To assess early clinical results and evaluate patient satisfaction in
      case of second conservative treatment (2nd CT) combining lumpectomy plus high
      dose rate (HDR) interstitial brachytherapy for patients (pts) presenting with
      ipsilateral breast cancer recurrence (IBCR). METHODS AND MATERIALS: From June
      2005 to July 2009, 42 pts presenting with an IBCR underwent a second lumpectomy
      with intraoperative implantation of plastic tubes in the tumor bed. After
      performing the dose distribution analysis on the postimplant CT scan, a total
      dose of 34 Gy in 10 fractions over 5 consecutive days was delivered. Toxicity
      evaluation was based on the Common Terminology Criteria for Adverse Events v3.0
      criteria. Applying a visual analogic scale (VAS) analysis, patient satisfaction
      regarding cosmetic result and 2nd CT possibility was performed after the end of
      brachytherapy. RESULTS: Median followup was 21 months (range, 6-50 months) and
      median age at the time of local recurrence was 65 years (range, 30-85 years).
      Median delay between primary and recurrence was 11 years (range, 1-35 years).
      Median recurrence tumor size was 12 mm (range, 2-30 mm). Median number of plastic
      tubes and planes were nine (range, 5-12) and two (range, 1-3), respectively.
      Median clinical target volume was 68 cc (range, 31.2-146 cc). Second local
      control rate was 97%. Twenty-two pts (60%) developed complications. Cutaneous and
      subcutaneous fibrosis was the most frequent side effect. Median VAS satisfaction
      score regarding cosmetic result was 7 of 10 (range, 4-9), whereas median VAS
      satisfaction score for 2nd CT was 10 of 10 (range, 8-10). CONCLUSION: A 2nd CT
      for IBCR using high-dose rate brachytherapy seems feasible with encouraging
      results in terms of second local control with an acceptable toxicity. Patient
      satisfaction regarding the possibility of second breast preservation should be
      considered.

PMID- 20685179
TI  - Optimization of high-dose-rate intracavitary brachytherapy schedule in the
      treatment of carcinoma of the cervix.
AB  - PURPOSE: At our institute, we use high-dose-rate (HDR) intracavitary
      brachytherapy (ICBT) schedule of 9 Gy per fraction for two fractions after
      external beam radiotherapy (EBRT) in patients with advanced carcinoma of the
      cervix. But American Brachytherapy Society recommends that individual fraction
      size should be less than 7 Gy per fraction in such patients. We present the
      results of comparison of our institution standard schedule with biologically
      equivalent dose of 6.8 Gy per fraction for three fractions in terms of local
      control, disease-free survival, and late toxicity. METHODS AND MATERIALS: Between
      October 2003 and August 2007, 104 patients with carcinoma of the uterine cervix
      (Stages IIB and IIIB) were treated with EBRT and HDR ICBT. After EBRT, patients
      were randomized to one of the treatment arms. ICBT dose in Control Arm A (n=52)
      was 9 Gy per fraction in two fractions, 1 week apart, and in Study Arm B (n=52),
      it was 6.8 Gy per fraction in 3 fractions, 1 week apart. RESULTS: The median
      followup was 31.48 months. The 3-year actuarial local control was 81.35% in Arm A
      and 65.18% in Arm B (p=0.0423), and the 3-year actuarial disease-free survival
      was 64.97% in Arm A and 49.47% in Arm B (p=0.0393). The 3-year actuarial risk of
      developing any Grade 3 or worse late toxicity was 7.47% in Arm A and 3.57% in Arm
      B (p=0.2907). CONCLUSION: In our setup, HDR brachytherapy at 9 Gy per fraction in
      two fractions is safe and effective with good local control, survival, and
      manageable normal tissue toxicity.

PMID- 20685180
TI  - Quantitative estimation of doses to salivary glands from using brachytherapy in
      head and neck cancers.
AB  - PURPOSE: To quantify the percentage doses received by salivary glands (SGDs) in
      head and neck interstitial brachytherapy (BT). METHODS AND MATERIALS: The study
      included 43 patients who underwent high-dose rate iridium-192 implant for oral
      cavity and oropharyngeal lesions treated with BT as a boost. BT dose varied with
      disease stage and external radiation dose, with the total mean dose of 66+/-4Gy.
      Patients were divided into two groups, midline and lateralized, based on anatomic
      implant location. Different dose parameters such as D(max), D(mean), DV(30%) of
      individual glands were derived from dose volume histogram representing the
      percentage maximum dose, mean dose, and dose received by 30% volume of individual
      SGDs, respectively. For better perception of the impact of BT on individual SGDs,
      the doses received are extrapolated to radical BT dose of 60Gy. RESULTS: For
      lateralized implants, the highest dose received by ipsilateral parotid (PTD) was
      12.3% seen in tonsillar implants. The contralateral PTD receives minimal doses.
      As expected, the ipsilateral submandibular gland (SMG) received high doses in the
      range of 80% of the total prescribed dose, whereas contralateral SMG received 10%
      of ipsilateral dose. For the midline implants, the mean dose range for PTD was 7
      11% of the total prescribed dose and for SMG between 17% and 56%, depending on
      the location. CONCLUSIONS: The study quantifies the percentage doses received by
      the individual SGDs in interstitial head and neck BT for use in future planning
      of the BT procedures and for salivary functional studies, prediction of damage,
      and quality-of-life parameters.

PMID- 20685181
TI  - Functional and morphological examinations of P1A1 purinoceptors in the normal and
      inflamed urinary bladder of the rat.
AB  - The aim of the present study was to investigate the relaxatory function of
      adenosine receptor subtypes in rat urinary bladder, and if it is altered in the
      state of inflammation. The in vitro responses to the P1 receptor agonist
      adenosine were investigated in the presence of the general P2 receptor antagonist
      pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS; 1*10(-4)M).
      Experiments were performed on preparations from normal (healthy) rats and rats
      with cyclophosphamide (CYP; 100mg kg(-1) i. p.)-induced cystitis. The specific
      P1A(1) antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX; 1*10(-5)M) decreased
      the adenosine relaxatory response in normal bladders (-60%), but not in
      preparations from CYP pre-treated rats. Immunohistochemical findings support the
      hypothesis that the expression of P1A(1) receptors in the rat urinary bladder is
      decreased during cystitis. The adenosine-evoked relaxation was not affected by
      the specific P1A(2A) antagonist SCH 58261 (3*10(-7)M), neither in normal nor in
      CYP pre-treated rats. The relaxation to adenosine was, however, significantly
      increased by the specific P1A(3) antagonist MRS 1523 (1*10(-5)M) in preparations
      from both normal and CYP pre-treated rats, suggesting P1A(3) to be mediating
      bladder contraction. Thus, in the rat urinary bladder the relaxation to adenosine
      is mainly due to the P1A(1) receptor, while the P1A(3) receptor seems to be
      responsible for contractile responses. The DPCPX-resistant part of the relaxation
      is possibly due to the P1A(2B) receptor, the fourth subtype of the adenosine
      receptor family.

PMID- 20685182
TI  - Inflammation contributes to axon reflex vasodilatation evoked by iontophoresis of
      an alpha-1 adrenoceptor agonist.
AB  - Iontophoresis of alpha(1)-adrenoceptor agonists in the human forearm evoke axon
      reflex vasodilatation, possibly due to an accumulation of inflammatory agents at
      the site of iontophoresis. To investigate this possibility, skin sites in the
      forearm of healthy participants were treated with an anti-inflammatory gel
      containing ibuprofen 5% before the iontophoresis of the alpha(1)-adrenoceptor
      agonist phenylephrine (350MUA for 3min). Red cell flux was measured with laser
      Doppler flowmetry at the site of iontophoresis and 8mm away in the region of axon
      reflex vasodilatation. In additional experiments, skin sites were treated with
      the vasodilator sodium nitroprusside (to counteract vasoconstriction and disperse
      inflammatory mediators produced during the iontophoresis of phenylephrine); local
      anaesthetic agent (to determine whether the axon reflex to phenylephrine was
      neurally-mediated); or the alpha(2)-adrenoceptor agonist clonidine (to
      investigate the specificity of the adrenergic axon reflex). Phenylephrine evoked
      marked vasodilatation 8mm from the site of iontophoresis whereas clonidine and
      saline-control did not (mean flux increase+/-S.E. 485+/-132% for phenylephrine;
      44+/-24% for clonidine; 39+/-19% for saline-control; p<0.05 for phenylephrine
      versus control). Axon reflex vasodilatation to phenylephrine was unaffected by
      variations in blood flow at the site of phenylephrine iontophoresis, but was
      reduced by ibuprofen pretreatment and abolished by local anaesthetic
      pretreatment. These findings suggest that prostaglandin synthesis at the site of
      iontophoresis contributes to but does not account entirely for axon reflex
      vasodilatation to phenylephrine. Alpha-1 adrenoceptor mediation of axon reflexes
      could play a role in aberrant sensory-sympathetic coupling in neuro-inflammatory
      diseases.

PMID- 20685183
TI  - A sensitive and selective liquid chromatography/tandem mass spectrometry method
      for determination of MLN8237 in human plasma.
AB  - We describe a selective and a highly sensitive high-performance liquid
      chromatography-electron spray ionization-collision induced dissociation-tandem
      mass spectrometry (HPLC-ESI-CID-MS/MS) assay for the Aurora A kinase inhibitor
      MLN8237 in human plasma. The intra-day precision based on the standard deviation
      of replicates of quality control samples ranged from 0.2 to 4% and with accuracy
      ranging from 96 to 102%. The inter-day precision ranged from 0.5 to 7% and the
      accuracy ranged from 93 to 105%. Stability studies showed that MLN8237 was stable
      both during the expected conditions for sample preparation and storage. The lower
      limit of quantification for MLN8237 was 5 ng/mL. The analytical method showed
      excellent sensitivity, precision, and accuracy. This method is robust and is
      being successfully employed in a Children's Oncology Group Phase 1 Consortium
      study of MLN8237 in children with cancer.

PMID- 20685185
TI  - [Compartment syndrome after cardiopulmonary bypass].
AB  - Compartment syndrome of the lower leg is an occasional complication of prolonged
      ischemia and reperfusion. We present a patient with compartment syndrome of the
      ipsilateral thigh after femoral arterial and venous cannulation for
      cardiopulmonary bypass.

PMID- 20685184
TI  - [Is our approach to thyroid nodules and differentiated thyroid carcinoma in
      agreement with the American guideline and European consensus?].
AB  - INTRODUCTION: The aim of this study was to assess the approaches of specialists
      in Spain to patients with thyroid nodules and differentiated thyroid carcinoma
      and to compare them with the American guideline and European consensus. MATERIAL
      AND METHODS: We performed a cross-sectional study based on a questionnaire
      addressed to clinical endocrinologists specialized in thyroid cancer and
      specialists in nuclear medicine throughout Spain. RESULTS: A total of 177
      questionnaires were completed, representing an overall response rate of 85%; 74%
      of responses were from endocrinologists and 24% from physicians active in nuclear
      medicine; 82% of respondents worked in third-level hospitals, 10% in second level
      hospitals and the remainder in private practice. Most used ultrasonography and
      cytology to assess thyroid nodules and collaborated with a group of surgeons
      expert in thyroid surgery. The majority preferred total or subtotal thyroidectomy
      in tumors with a diameter of 1 cm or more, and systematic lymph node dissection.
      Only 43 (24%) preferred prophylactic central lymph node dissection. Eighty-one
      respondents (45%) would still use whole body scan with 131I or 123I before 131I
      ablation. Follow-up was based on cervical echography and thyroglobulin
      determination; however, 101 (57%) respondents continued to use diagnostic whole
      body scan in the follow-up. CONCLUSION: The approaches of the respondents were
      mainly in accordance with the guideline and consensus, although some variations
      were found, especially in the use of whole body scan with 131I before ablation
      and in follow-up.

PMID- 20685186
TI  - Microarray technology is an effective tool for identifying genes related to the
      aquacultural improvement of Japanese flounder, Paralichthys olivaceus.
AB  - Molecular techniques are now essential for discovering new functional genes for
      the improvement of cultured marine organisms. Such techniques can be used to
      obtain expressed sequence tags (EST) and, through the use of microarrays, the
      entire transcriptome. For example, microarrays can be used to reveal biomarkers
      of health conditions, nutrient changes and immune response in fish and shellfish.
      EST-based microarray chips were constructed for cultured fish and shellfish
      species including Japanese flounder (Paralichthys olivaceus). Using the flounder
      microarray chip, the efficacy of two DNA vaccines derived from pathogenic viruses
      [hirame rhabdovirus (HRV) and viral hemorrhagic septicemia virus (VHSV)] was
      evaluated through gene expression profiles. The results suggest that both DNA
      vaccines were effective in protecting the flounder from HIRRV and VHSV. The
      flounder microarray was also used to compare gene expression patterns in fish
      that are susceptible and resistant to Edwardsiella tarda. At 3days post
      infection, the gene expression patterns between the two groups were dramatically
      changed. Thus, microarray analysis is a very powerful tool to understand gene
      expression profiles in fish.

PMID- 20685187
TI  - The 'Butter Test' to guide effective tissue cleansing after high-pressure
      injection injury.
AB  - A case of high-pressure fingertip injury with an unknown paint primer injectate,
      and the use of a simple test to determine whether it is water- or solvent-based
      in order to guide subsequent optimal debridement, is presented. The favourable
      outcome achieved was felt to have resulted, in part, from the effective single
      debridement thus achieved.

PMID- 20685188
TI  - Allele frequencies and concordance study between the Identifiler and the
      PowerPlex ESX17 systems in the Basque Country population.

PMID- 20685189
TI  - Analysis of 11 tetrameric STRs in wild boars for forensic purposes.
AB  - STR profiling of animal species has a wide range of applications, including
      forensic identification, wildlife preservation, veterinary public health
      protection and food safety. We tested the efficacy of a multiplex PCR-based assay
      including 11 porcine-specific tetrameric STRs in a population sample of wild
      boars (n=142) originating from Piedmont (North West Italy). Multiple deviations
      from Hardy-Weinberg expectations were observed, mostly due to a reduction in
      observed heterozygosity indicative of a high degree of inbreeding. A value of
      theta of 0.046 and an inbreeding coefficient of 0.089 were estimated. Combined
      power of discrimination and probability of exclusion values for the STR panel
      were 0.9999999999996 and 0.99989. In order to test the suitability of the method
      for meat traceability purposes, a domestic pig reference sample (n=412),
      consisting of commercial lines commonly used in the meat production process, was
      also typed. A Bayesian cluster analysis carried out using the observed genotypes,
      showed a percentage of correct subspecies assignment of individual samples of
      0.974 for wild boars and 0.991 for pigs, thus demonstrating the usefulness of the
      multiplex STR-typing system for discrimination purposes.

PMID- 20685191
TI  - Making research matter: promoting dissemination and sustainability.

PMID- 20685190
TI  - Training clinicians in mental health communication skills: impact on primary care
      utilization.
AB  - OBJECTIVE: Although it is known that children with mental health problems utilize
      primary care services more than most other children, it is unknown how addressing
      mental health problems in primary care affects children's subsequent services
      utilization. This study measures primary care utilization in the context of a
      randomized trial of a communication skills training program for primary care
      clinicians that had a positive impact on child mental health outcomes. METHODS:
      From 2002 to 2005, 48 pediatric primary care clinicians at 13 sites in rural
      upstate New York, urban Maryland, and Washington, DC, were randomized to in
      office training or to a control group. Consecutive primary care patients between
      the ages of 5 and 16 years were screened for mental health problems, as indicated
      by a possible or probable score on the Strengths and Difficulties Questionnaire
      (SDQ). For 397 screened children, primary care visits during the next 6 months
      were identified using chart review and administrative databases. Using
      generalized estimating equation regression to account for clustering at the
      clinician level, primary care utilization was compared by study group and SDQ
      status. RESULTS: The number of primary care visits to the trained clinicians did
      not differ significantly from those made to control clinicians (2.5 for both
      groups; P = .63). Children with possible or probable SDQ scores made, on average,
      0.38 or 0.65 more visits on a per child basis, respectively, during the 6-month
      follow-up period than SDQ unlikely children (P = .0002). CONCLUSIONS: Seeing a
      trained clinician did not increase subsequent primary care utilization. However,
      primary care utilization was greater among children with mental health problems
      as measured by the SDQ. Addressing children's mental health in primary care does
      not increase the primary care visit burden. Research on overall health services
      utilization is needed.

PMID- 20685192
TI  - The role of the doctor and the medical system in the diagnostic delay in
      pediatric malignancies.
AB  - AIM: We evaluated the roles of the doctor and the medical system in Israel in the
      diagnostic delay of childhood malignancies. METHODS: We investigated the factors
      affecting the delay in the diagnosis of childhood malignancies in 315 children
      with solid malignancies, diagnosed and treated in Rambam Medical Center (RMC),
      between 1993 and 2001. Those factors were divided into two groups: 'Healthcare
      system-related parameters', (factors directly related to the medical system), and
      'Patient-related parameters' (factors that are not part of the medical system,
      but directly affect medical judgment and decisions, including factors related to
      the tumor). We also took into consideration epidemiological, social, and medical
      issues. RESULTS: The main 'Healthcare-system-related parameters', which were
      found to influence the delay in diagnosis, were the type of medical authority
      that was initially consulted; the specialty of the first doctor; the number of
      additional doctors whom the child had visited, and the number of times the child
      had visited the first doctor. The main 'Patient-related parameters' found to have
      an impact on the delay in diagnosis were the age of the child, the tumor type,
      and the presenting symptom. CONCLUSIONS: The education and awareness of doctors
      at the primary healthcare clinics must be improved. We suggest ways of improving
      the approach of doctors and managing a child with a suspected malignancy.

PMID- 20685193
TI  - Cancer related factors do not explain the quality of life scores for childhood
      cancer survivors analysed with two different generic HRQL instruments.
AB  - THE AIMS: The aims of this Finnish total cohort survey were to compare the health
      related quality of life (HRQL) of childhood cancer survivors with for age, gender
      and place of residence matched controls, to analyse whether the disease-related
      factors do explain the survivors scores, and to evaluate the similarity of HRQL
      scores gained with two different generic instruments. METHODS: Questionnaires (SF
      36 version 2 and the 15D) were mailed to 468 survivors and their controls.
      RESULTS: A total of 271 survivors and 329 controls replied. The survivors rated
      with both instruments their HRQL in most areas as high or higher than their
      controls. Mobility score was, however, significantly lower for survivors than
      controls. Females rated their HRQL lower than respective males. Self-rated
      happiness had the highest effect in explaining the variation of 15D and mental
      component summary (MCS) scores. Survivors treated for osteosarcoma or with stem
      cell transplantation (SCT) rated their physical HRQL significantly lower than the
      others. SCT treatment indicated significantly lower MCS scores than the reference
      treatment. Correlation between the physical component summary (PCS) scores and
      15D total scores was low (R=0.20-0.28). MCS and 15D total scores correlated
      (R=0.48-0.60) better with each other, but the gained correlation coefficients
      still differed significantly from each other (p=0.04) and showed better
      correlation in the controls. CONCLUSIONS: Our findings suggest, that the
      diagnosis of osteosarcoma, and SCT treatment are substantial risks for adverse
      HRQL. However, disease related factors did not remarkably explain the variation
      of HRQL scores gained with generic HRQL instruments. Our findings suggest, that
      the diagnosis of osteosarcoma, and SCT treatment are substantial risks for
      adverse HRQL. More evaluation is needed in order to decide whether any of the
      available generic instruments are feasible for studying HRQL for this special
      population.

PMID- 20685197
TI  - The role of low-density receptor-related protein 1 (LRP1) as a competitive
      substrate of the amyloid precursor protein (APP) for BACE1.
AB  - Cleavage of APP by BACE1 is the first proteolytic step in the production of
      amyloid-beta (Abeta), which accumulates in senile plaques in Alzheimer's disease.
      Through its interaction with APP, the low-density receptor-related protein 1
      (LRP1) enhances APP internalization. Recently, BACE1 has been shown to interact
      with and cleave the light chain (lc) of LRP1. Since LRP1 is known to compete with
      APP for cleavage by gamma-secretase, we tested the hypothesis that LRP1 also acts
      as a competitive substrate for beta-secretase. We found that the increase in
      secreted APP (sAPP) mediated by over-expression of BACE1 in APP-transfected cells
      could be decreased by simultaneous LRP1 over-expression. Analysis by multi-spot
      ELISA revealed that this is due to a decrease in sAPPbeta, but not sAPPalpha.
      Interaction between APP and BACE1, as measured by immunoprecipitation and
      fluorescence lifetime assays, was impaired by LRP1 over-expression. We also
      demonstrate that APP over-expression leads to decreased LRP1 association with and
      cleavage by BACE1. In conclusion, our data suggest that--in addition to its role
      in APP trafficking--LRP1 affects APP processing by competing for cleavage by
      BACE1.

PMID- 20685201
TI  - Azadirachta indica A. Juss (neem) induced morphological changes on oocytes of
      Rhipicephalus sanguineus (Latreille, 1806) (Acari: Ixodidae) tick females.
AB  - Many studies have been conducted with plants whose extracts have the potential to
      be used for pest control. One of these plants is Azadirachta indica (neem), whose
      main active ingredient is azadirachtin, a compound shown to have acaricide and
      insecticide activity. Rhipicephalus sanguineus (brown dog tick) is currently
      considered to be an "urban pest," because of its high levels of infestation and
      its ability to attack humans. In the present study partially and fully engorged
      R. sanguineus females were exposed to aqueous extracts of neem at concentrations
      of 10% and 20%, and to a control treatment. The results showed that differently
      from what was observed in the control, the pedicel cells of females exposed to
      neem at both concentrations lost their original shape. In the latter cases, the
      cytoplasm of the cells became fully vacuolated, especially near the germinal
      vesicle (oocyte nuclei) and in the oocyte pole, which is in contact with the
      cells of the pedicel. Oocytes in early stages of development (I and II) of ticks
      treated with both concentrations had irregular germinal vesicle, including the
      presence of two nucleoli as well as fragments of these. Oocytes in stages IV and
      V of exposed individuals showed full granular cytoplasm with bigger yolk granules
      when compared to the early stages. Chorion of mature oocytes was also altered,
      showing folds and deformations along their entire extension. The observed changes
      in cells of the reproductive system of R. sanguineus, especially in the oocytes,
      indicated the potential of neem as a new alternative method to control these
      ectoparasites.

PMID- 20685202
TI  - Schistosoma japonicum: efficient and rapid purification of the tetraspanin
      extracellular loop 2, a potential protective antigen against schistosomiasis in
      mammalian.
AB  - The extracellular loop 2 of a tetraspanin from Schistosoma japonicum (Sj-TSP-2)
      is homologous to Schistosoma mansoni TSP-2. In our initial study, Sj-TSP-2 is an
      identical antigen against schistosomiasis caused by S. japonicum. Through the
      pET32 vector system and nickel (Ni)-absorbed chelating Sepharose, Sj-TSP-2 was
      expressed and purified as a soluble fusion constructed with an N-terminal
      thioredoxin-His(6)-EK protease site tag (Trx-TSP-2). In phosphate buffer (PB)
      with a low concentration of imidazole, the Trx-TSP-2 fusion protein was
      efficiently cleaved by enterokinase (EK). Sj-TSP-2 was isolated and enriched
      using cobalt (Co)-absorbed chelating Sepharose and HiTrap SP column. Character of
      the protein was analyzed via animal experiments and then clinical trials. The
      purification approach yielded pure Sj-TSP-2, which will provide feasible advices
      for discovering vaccines against schistosomiasis.

PMID- 20685203
TI  - Leishmania tarentolae: utility as an in vitro model for screening of
      antileishmanial agents.
AB  - Primary screens for antileishmanial compounds use Leishmania species pathogenic
      to humans that must be handled under biosafety conditions that cannot be adopted
      or guaranteed everywhere. Leishmania tarentolae, a parasite isolated from the
      gecko Tarentolae annularis, has not been considered pathogenic to humans.
      Promastigotes of L. tarentolae have been previously used as a eukaryotic
      expression system for the production of recombinant proteins and in the
      amplification of genes involved in resistance to antileishmanial drugs. To
      validate the use of this Leishmania species in the screening of antileishmanial
      drugs, the sensitivity of axenic and intracellular amastigotes of L. tarentolae
      was compared to the sensitivity showed by Leishmania species causative of human
      leishmaniasis. The ability of L. tarentolae to grow as axenic amastigotes is
      first described while its ability to infect several mammalian cells has been
      confirmed. L. tarentolae amastigotes offer a suitable model for the in vitro
      screening of compounds for antileishmanial activity.

PMID- 20685204
TI  - Fatty acid metabolism in the liver, measured by positron emission tomography, is
      increased in obese individuals.
AB  - BACKGROUND & AIMS: Hepatic lipotoxicity results from and contributes to obesity
      related disorders. It is a challenge to study human metabolism of fatty acids
      (FAs) in the liver. We combined (11)C-palmitate imaging by positron emission
      tomography (PET) with compartmental modeling to determine rates of hepatic FA
      uptake, oxidation, and storage, as well as triglyceride release in pigs and human
      beings. METHODS: Anesthetized pigs underwent (11)C-palmitate PET imaging during
      fasting (n = 3) or euglycemic hyperinsulinemia (n = 3). Metabolic products of FAs
      were measured in arterial, portal, and hepatic venous blood. The imaging
      methodology then was tested in 15 human subjects (8 obese subjects); plasma (11)C
      palmitate kinetic analyses were used to quantify systemic and visceral lipolysis.
      RESULTS: In pigs, PET-derived and corresponding measured FA fluxes (FA uptake,
      esterification, and triglyceride FA release) did not differ and were correlated
      with each other. In human beings, obese subjects had increased hepatic FA
      oxidation compared with controls (mean +/- standard error of the mean, 0.16 +/-
      0.01 vs 0.08 +/- 0.01 micromol/min/mL; P = .0007); FA uptake and esterification
      rates did not differ between obese subjects and controls. Liver FA oxidation
      correlated with plasma insulin levels (r = 0.61, P = .016), adipose tissue (r =
      0.58, P = .024), and systemic insulin resistance (r = 0.62, P = .015). Hepatic FA
      esterification correlated with the systemic release of FA into plasma (r = 0.71,
      P = .003). CONCLUSIONS: PET imaging can be used to measure FA metabolism in the
      liver. By using this technology, we found that obese individuals have increased
      hepatic oxidation of FA, in the context of adipose tissue insulin resistance, and
      increased FA flux from visceral fat. FA flux from visceral fat is proportional
      with the mass of the corresponding depot.

PMID- 20685205
TI  - Neurotrophic factor delivery as a protective treatment for glaucoma.
AB  - Glaucoma is a progressive optic neuropathy and a major cause of visual impairment
      worldwide. Neuroprotective therapies for glaucoma aim to ameliorate retinal
      ganglion cell degeneration through direct or indirect action on these neurons.
      Neurotrophic factor (NTF) delivery is a key target for the development of
      potential neuroprotective glaucoma treatments. This article will critically
      summarize the evidence that NTF deprivation and/or dysfunction plays a role in
      the pathogenesis of glaucoma. Experimental support for the neuroprotective
      potential of NTF supplementation in animal models of glaucoma will be reviewed,
      in particular for brain-derived neurotrophic factor, ciliary neurotrophic factor,
      and glial cell line-derived neurotrophic factor. Finally, the challenges of
      clinical translation will be considered with an emphasis on the most promising
      NTF delivery strategies including slow-release drug delivery, gene therapy, and
      cell transplantation.

PMID- 20685206
TI  - Nonlinear temporal organization of neuronal discharge in the basal ganglia of
      Parkinson's disease patients.
AB  - Previous electrophysiological studies of the basal ganglia in Parkinson's disease
      (PD) patients have utilized linear analyses in time-or-frequency-domains to
      characterize neuronal discharge patterns. However, these measures do not fully
      describe the non-linear features of discharge rates and oscillatory activities of
      basal ganglia neurons. In this original research, we investigate whether non
      linear temporal organizations exist in the inter-spike interval series of neurons
      recorded in the globus pallidus or the subthalamic nucleus in PD patients
      undergoing surgery for the implantation of deep brain stimulating electrodes. Our
      data indicate that in approximately 80% of globus pallidus and subthalamic
      neurons, the raw inter-spike interval sequences have lower entropy values than
      those observed after shuffling of the original series. This is the first report
      establishing non-linear temporal organization as a common feature of neuronal
      discharge in the basal ganglia of PD patients.

PMID- 20685208
TI  - Detecting and differentiating Theileria sergenti and Theileria sinensis in cattle
      and yaks by PCR based on major piroplasm surface protein (MPSP).
AB  - Theileria sergenti and Theileria sinensis are closely related members of benign
      Theileria species found in cattle and yaks in China. They are morphologically
      indistinguishable. A polymerase chain reaction (PCR) targeting major piroplasm
      surface protein of T. sergenti and T. sinensis was developed in this study. The
      newly developed oligonucleotide primer set was able to specifically amplify the
      DNA of T. sinensis and in conjunction with primers for T. sergenti and these two
      species could be detected and distinguished. Specificity testing also revealed
      that there was no cross-reaction with the other tick-borne diseases Theileria
      annulata, Babesia ovata, Anaplasma marginale as well as bovine white blood cells.
      Phylogenetic analysis based on the MPSP gene sequences confirmed the specificity
      of PCR assays. The sensitivity of the methods was 0.1pg DNA for the T. sergenti
      PCR and 1pg DNA for T. sinensis PCR. Two hundred and thirty-six field blood
      samples from of cattle and yaks were collected from five different geographical
      regions in China where benign Theileria species have been found. T. sergenti was
      found in all five provinces but was absent from one county in Gansu Province. T.
      sinensis was only found in Gansu Province. In both counties in Gansu where the
      parasites co-existed, mixed infections were detected. Our results indicate that
      the PCR methods developed in this study are suitable for the detection and
      differentiation of T. sergenti and T. sinensis.

PMID- 20685209
TI  - Host immune response to Cryptosporidium parvum infection.
AB  - Species of the genus Cryptosporidium are protozoan parasites (Apicomplexa) that
      cause gastroenteritis in animals and humans. Of these Cryptosporidium parvum and
      Cryptosporidium hominis are the major causative agents of human
      cryptosporidiosis. Whereas infection is self-limiting in the immunocompetent
      hosts, immunocompromised individuals develop a chronic, life-threatening disease.
      As specific therapeutic or preventive interventions are not yet available, better
      understanding of the immune response to the parasite is required. This minireview
      briefly summarizes the factors involved in the innate and acquired immune
      response in this pathogen-host interaction with an emphasis on more recent data
      from mouse models of infection.

PMID- 20685210
TI  - Parasitic infection leads to decline in hemolymph sugar levels in honeybee
      foragers.
AB  - Parasites by drawing nutrition from their hosts can exert an energetic stress on
      them. Honeybee foragers with their high metabolic demand due to flight are
      especially prone to such a stress when they are infected. We hypothesized that
      infection by the microsporidian gut parasite Nosema ceranae can lower the
      hemolymph sugar level of an individual forager and uncouple its energetic state
      from its normally tight correlation with the colony energetic state. We support
      our hypothesis by showing that free-flying foragers that are infected have lower
      trehalose levels than uninfected ones but the two do not differ in their
      trehalose levels when fed until satiation. The trehalose level of infected bees
      was also found to decline at a faster rate while their glucose level is
      maintained at a quantity comparable to uninfected bees. These results suggest
      that infected foragers have lower flying ability and the intriguing possibility
      that the carbohydrate levels of an individual bee can act as a modulator of its
      foraging behavior, independent of social cues such as colony demand for nectar.
      We discuss the importance of such pathophysiological changes on foraging behavior
      in the context of the recently observed colony collapses.

PMID- 20685211
TI  - Effects of fluctuating moisture and temperature regimes on the persistence of
      quiescent conidia of Isaria fumosorosea.
AB  - Conidia of Isaria fumosorosea were submitted to three regimes of temperature and
      moisture to simulate microclimatic conditions which prevail in temperate (43% RH
      and 28 degrees C to 98% RH and 15 degrees C), subtropical (75% RH and 35 degrees
      C to 98% RH and 25 degrees C), and arid areas (13% RH and 40 degrees C to 33% RH
      and 15 degrees C) with daily fluctuating cycles. Germination, conidial viability,
      and virulence to Spodoptera frugiperda larvae were less affected after 20 days
      exposure under temperate cycling conditions than under arid and subtropical
      conditions. Exposure of conidia for 20 days to constant nocturnal simulated
      conditions of any tested regime weakly affected conidial persistence, whereas
      diurnal conditions exerted the most detrimental effects of high temperatures.
      However, when tested at both 45 degrees C and 50 degrees C at 33% RH for 160 h,
      the persistence of I. fumosorosea conidia was relatively higher than expected.
      These results emphasize that climatic conditions prevailing in environments and
      ecological fitness of fungal isolates have to be taken into account for assessing
      microbial control strategies.

PMID- 20685215
TI  - Effect of agomelatine and its interaction with the daily corticosterone rhythm on
      progenitor cell proliferation in the dentate gyrus of the adult rat.
AB  - Agomelatine, a novel melatonin analogue and anti-depressant that acts as an
      agonist on melatonin receptors 1 and 2 and as an antagonist at the 5HT2C
      receptor, was tested for its effects on cell proliferation in the dentate gyrus
      of the adult rat hippocampus under intact and flattened corticosterone rhythm
      conditions. Agomelatine stimulated mitosis rates in the intact male rat.
      Flattening the daily corticosterone rhythm by inserting a subcutaneous pellet of
      this steroid prevented the action of agomelatine. However, adding a daily
      injection of corticosterone at CT1200 to rats with implanted corticosterone
      pellets failed to restore agomelatine's efficacy on cell proliferation. The 5HT2C
      receptor antagonist SB242084 stimulated progenitor cell proliferation in the
      dentate gyrus, while a 5HT2C agonist (RO600175) had no effect on cell
      proliferation alone, but counteracted that of agomelatine. These results suggest
      that agomelatine, a new anti-depressant, can stimulate progenitor cell mitosis in
      the dentate gyrus. Its action requires an intact diurnal corticosterone rhythm.
      The action of agomelatine on neurogenesis is likely to reside in its antagonism
      of the 5HT2C receptor, and suggests a mechanism distinct from that of fluoxetine,
      another anti-depressant, which, as previous work shows, acts through the 5HT1A
      receptor, but whose action is also blocked by a flattened corticosterone rhythm.

PMID- 20685216
TI  - Alpha-glucosidase and tyrosinase inhibitors from fungal hydroxylation of tibolone
      and hydroxytibolones.
AB  - Sixteen new and one known metabolites 4-20 were obtained by incubation of
      tibolone (1) and hydroxytibolones (2 and 3) with various fungi. Their structures
      were elucidated by means of a homo and heteronuclear 2D NMR and by HREI-MS
      techniques. The relative stereochemistry was deduced by 2D NOESY experiment.
      Metabolites of tibolone (1) exhibited significant inhibitory activities against
      alpha-glucosidase and tyrosinase enzymes. Hydroxylations at C-6, C-10, C-11, C-15
      positions and alpha,beta-unsaturation at C-1/C-2, C-4/C-5 showed potent
      inhibitory activities against these enzymes.

PMID- 20685217
TI  - Pd(PPh(3))(4)/AgOAc-catalyzed coupling of 17-steroidal triflates and alkynes:
      Highly efficient synthesis of D-ring unsaturated 17-alkynylsteroids.
AB  - A novel and practical procedure was developed for the preparation of D-ring
      unsaturated 17-alkynyl steroids by Pd(PPh(3))(4)/AgOAc-catalyzed coupling of
      steroidal 17-triflates and alkynes. Firstly treatment of the steroid-17-ones with
      PhN(Tf)(2) and KHMDS in dried THF at -78 degrees C for 2h gives the corresponding
      steroidal 17-triflates products in high yields (97-98%), following the coupling
      of steroidal 17-triflates and various 1-alkynes by Pd(PPh(3))(4)/AgOAc-catalyzed
      in the presence of DIPEA for 24h to yield the desired D-ring unsaturated 17
      alkynyl steroids (86-97%). Moreover, it was found that the coupling reaction
      catalyzed by Pd[(C(6)H(5))(3)P](4)/AgOAc system is selective for aryl triflates
      or vinyl triflates. By optimizing the reaction conditions, the sole C17-coupling
      products from steroidal bistriflates were obtained in satisfactory yields. Since
      D-ring unsaturated 17-alkynyl steroids with conjugated double and triplet bond
      can be subsequently converted into pentacyclic steroids and 17-oxosteroid
      derivatives at the side chain of D-ring, this general method provides a highly
      efficient route to these biologically important compounds.

PMID- 20685218
TI  - A coalescent dual process in a Moran model with genic selection, and the lambda
      coalescent limit.
AB  - The genealogical structure of neutral populations in which reproductive success
      is highly-skewed has been the subject of many recent studies. Here we derive a
      coalescent dual process for a related class of continuous-time Moran models with
      viability selection. In these models, individuals can give birth to multiple
      offspring whose survival depends on both the parental genotype and the brood
      size. This extends the dual process construction for a multi-type Moran model
      with genic selection described in Etheridge and Griffiths (2009). We show that in
      the limit of infinite population size the non-neutral Moran models converge to a
      Markov jump process which we call the lamda-Fleming-Viot process with viability
      selection and we derive a coalescent dual for this process directly from the
      generator and as a limit from the Moran models. The dual is a branching
      coalescing process similar to the Ancestral Selection Graph which follows the
      typed ancestry of genes backwards in time with real and virtual lineages. As an
      application, the transition functions of the non-neutral Moran and lamda
      coalescent models are expressed as mixtures of the transition functions of the
      dual process.

PMID- 20685220
TI  - Cuprizone neurotoxicity, copper deficiency and neurodegeneration.
AB  - Cuprizone is used to obtain demyelination in mice. Cuprizone-treated mice show
      symptoms similar to several neurodegenerative disorders such as severe status
      spongiosus. Although it has a simple chemical formula, its neurotoxic mechanism
      is still unknown. In this work, we examined both physico-chemical properties and
      biological effects of cuprizone. Our results indicate that cuprizone has very
      complicated and misunderstood solution chemistry. Moreover, we show here the
      inability of cuprizone to cross neither the intestinal epithelial barrier nor the
      neuronal cell membrane, as well its high tolerability by cultured neurons. If
      added to mice diet, cuprizone does not accumulate in liver or in brain.
      Therefore, its neurotoxic effect is explainable only in terms of its capability
      to chelate copper, leading to chronic copper deficiency.

PMID- 20685221
TI  - Looking at the blood-brain barrier: molecular anatomy and possible investigation
      approaches.
AB  - The blood-brain barrier (BBB) is a dynamic and complex interface between blood
      and the central nervous system that strictly controls the exchanges between the
      blood and brain compartments, therefore playing a key role in brain homeostasis
      and providing protection against many toxic compounds and pathogens. In this
      review, the unique properties of brain microvascular endothelial cells and
      intercellular junctions are examined. The specific interactions between
      endothelial cells and basement membrane as well as neighboring perivascular
      pericytes, glial cells and neurons, which altogether constitute the neurovascular
      unit and play an essential role in both health and function of the central
      nervous system, are also explored. Some relevant pathways across the endothelium,
      as well as mechanisms involved in the regulation of BBB permeability, and the
      emerging role of the BBB as a signaling interface are addressed as well.
      Furthermore, we summarize some of the experimental approaches that can be used to
      monitor BBB properties and function in a variety of conditions and have allowed
      recent advances in BBB knowledge. Elucidation of the molecular anatomy and
      dynamics of the BBB is an essential step for the development of new strategies
      directed to maintain or restore BBB integrity and barrier function and ultimately
      preserve the delicate interstitial brain environment.

PMID- 20685223
TI  - Optimization of vincristine-topotecan combination--paving the way for improved
      chemotherapy regimens by nanoliposomes.
AB  - There is an opportunity to improve the therapeutic potential of a combination of
      two drugs using nanoliposomes. The combination of topotecan (TPT) and vincristine
      (VCR) was selected. The ratio-dependent synergy between these two drugs was
      evaluated, in an attempt to improve the therapeutic efficacy of this combination
      in vivo. The interaction between the drugs was evaluated in tissue culture by the
      median-effect analysis. Certain ratios of combined drugs were synergistic,
      whereas, others were antagonistic, implying that the most efficacious
      combinations should be at a specific fixed drug ratio. For in vivo evaluation,
      nanoliposomes co-remotely loaded simultaneously with both drugs by transmembrane
      ammonium sulfate gradient were developed. VCR and TPT were successfully co
      encapsulated at therapeutically relevant levels in the same nanoliposome
      (LipoViTo). The nanoliposomes controlled the drugs' "biofate" and maintained a
      fixed drug ratio in vivo, allowing one to compare the therapeutic efficacy of
      various predefined drug ratios. Pharmacokinetics and biodistribution studies
      showed that LipoViTo delivers the two drugs simultaneously to the tumors, where
      they are released at a predefined ratio. LipoViTo was more efficacious than the
      free drugs and liposomes with one agent, singly or in combination, in two tumor
      models in mice. LipoViTo co-loaded with both drugs corresponding to their maximal
      tolerated dose (MTD) ratio resulted in the best therapeutic efficacy. To
      summarize: liposomal co-encapsulation of anticancer drug combinations can
      profoundly influence therapeutic outcomes. Drug combinations can be optimized
      preclinically through pharmacokinetic control by remote loading into
      nanoliposomes.

PMID- 20685224
TI  - Superparamagnetic iron oxide nanoparticles (SPIONs): development, surface
      modification and applications in chemotherapy.
AB  - At present, nanoparticles are used for various biomedical applications where they
      facilitate laboratory diagnostics and therapeutics. More specifically for drug
      delivery purposes, the use of nanoparticles is attracting increasing attention
      due to their unique capabilities and their negligible side effects not only in
      cancer therapy but also in the treatment of other ailments. Among all types of
      nanoparticles, biocompatible superparamagnetic iron oxide nanoparticles (SPIONs)
      with proper surface architecture and conjugated targeting ligands/proteins have
      attracted a great deal of attention for drug delivery applications. This review
      covers recent advances in the development of SPIONs together with their
      possibilities and limitations from fabrication to application in drug delivery.
      In addition, the state-of-the-art synthetic routes and surface modification of
      desired SPIONs for drug delivery purposes are described.

PMID- 20685222
TI  - Hyperventilation in panic disorder and asthma: empirical evidence and clinical
      strategies.
AB  - Sustained or spontaneous hyperventilation has been associated with a variety of
      physical symptoms and has been linked to a number of organic illnesses and mental
      disorders. Theories of panic disorder hold that hyperventilation either produces
      feared symptoms of hypocapnia or protects against feared suffocation symptoms of
      hypercapnia. Although the evidence for both theories is inconclusive, findings
      from observational, experimental, and therapeutic studies suggest an important
      role of low carbon dioxide (CO2) levels in this disorder. Similarly, hypocapnia
      and associated hyperpnia are linked to bronchoconstriction, symptom exacerbation,
      and lower quality of life in patients with asthma. Raising CO2 levels by means of
      therapeutic capnometry has proven beneficial effects in both disorders, and the
      reversing of hyperventilation has emerged as a potent mediator for reductions in
      panic symptom severity and treatment success.

PMID- 20685225
TI  - ErbB receptor signaling in astrocytes: a mediator of neuron-glia communication in
      the mature central nervous system.
AB  - Astrocytes are now recognized as active players in the developing and mature
      central nervous system. Each astrocyte contacts vascular structures and thousands
      of synapses within discrete territories. These cells receive a myriad of inputs
      and generate appropriate responses to regulate the function of brain
      microdomains. Emerging evidence has implicated receptors of the ErbB tyrosine
      kinase family in the integration and processing of neuronal inputs by astrocytes:
      ErbB receptors can be activated by a wide range of neuronal stimuli; they control
      critical steps of glutamate-glutamine metabolism; and they regulate the
      biosynthesis and release of various glial-derived neurotrophic factors,
      gliomediators and gliotransmitters. These key properties of astrocytic ErbB
      signaling in neuron-glia interactions have significance for the physiology of the
      mature central nervous system, as exemplified by the central control of
      reproduction within the hypothalamus, and are also likely to contribute to
      pathological situations, since both dysregulation of ErbB signaling and glial
      dysfunction occur in many neurological disorders.

PMID- 20685228
TI  - Polyphenol contents and antioxidant activity of lyophilized aqueous extract of
      propolis from Erzurum, Turkey.
AB  - Propolis, an extremely complex resinous material, exhibits valuable
      pharmacological and biological properties attributed to the presence of
      polyphenols. In this study, we determined the antioxidant properties of
      lyophilized aqueous extract of propolis (LAEP) from Erzurum province of Turkey
      and correlated the values with total levels of polyphenolic compounds. In order
      to estimate the capacity of LAEP to act as antioxidants, we studied its 1,1
      diphenyl-2-picryl-hydrazyl radicals (DPPH()), 2,2'-azino-bis(3
      ethylbenzthiazoline-6-sulfonic acid) radicals (ABTS()(+)), N,N-dimethyl-p
      phenylenediamine radicals (DMPD()(+)), superoxide anion radicals (O(2)(-)) and
      hydrogen peroxide (H(2)O(2)) scavenging activity, total antioxidant activity,
      ferric ions (Fe(3+)) and cupric ions (Cu(2+)) reducing ability, ferrous ions
      (Fe(2+)) chelating activity. LAEP inhibited 93.2% lipid peroxidation of a
      linoleic acid emulsion at 30 microg/mL concentration. On the other hand, BHA,
      BHT, alpha-tocopherol and trolox displayed 83.3%, 82.1%, 68.1% and 81.3%
      inhibition of peroxidation at the same concentration, respectively. Quantitative
      amounts of caffeic acid, ferulic acid, syringic acid, ellagic acid, quercetin,
      alpha-tocopherol, pyrogallol, p-hydroxybenzoic acid, vanillin, p-coumaric acid,
      gallic acid and ascorbic acid were detected by high performance liquid
      chromatography and tandem mass spectrometry (LC-MS/MS). This study will bring an
      innovation for further studies with regard to the antioxidant properties of LAEP.

PMID- 20685229
TI  - Amyloid fibril formation by human stefins: Structure, mechanism & putative
      functions.
AB  - Many questions in the field of protein aggregation to amyloid fibrils remain
      open. In this review we describe predominantly in vitro studies of
      oligomerization and amyloid fibril formation by human stefins A and B. In human
      stefin B amyloidogenesis in vitro we have observed some general and many specific
      properties of its prefibrillar oligomers and amyloid fibrils. One characteristic
      feature in common to stefins and cystatins (and possibly some other amyloid
      proteins) is domain-swapping. In addition to solution structure of the domain
      swapped dimer of stefin A, we recently have determined 3D structure of stefin B
      tetramer, which proved to be composed from two domain-swapped dimers, whose
      interaction occurs by a proline switch in the loop surrounding the conserved Pro
      74. Studying the mechanism of fibril formation by stefin B, we found that the
      nucleation and fibril elongation reactions have energies of activation (E(a)'s)
      in the range of proline isomerisation, strongly indicating importance of the Pro
      at site 74 and/or other prolines in the sequence. Correlation between toxicity of
      the prefibrillar oligomers and their interaction with acidic phospholipids was
      demonstrated. Stefin B was shown to interact with amyloid-beta peptide of
      Alzheimer's disease in an oligomer specific manner, both in vitro and in the
      cells. It also has been shown that endogenous stefin B (with E at site 31) but
      especially the EPM1 mutant R68X and Y31-stefin B variant, and to a lesser extent
      EPM1 mutant G4R, are prone to form aggregates in cells.

PMID- 20685233
TI  - Of mice and men: human RNA polymerase III promoter U6 is more efficient than its
      murine homologue for shRNA expression from a lentiviral vector in both human and
      murine progenitor cells.
AB  - OBJECTIVE: RNA interference mediated by transcription of short hairpin RNAs
      (shRNAs) from lentiviral expression vectors has emerged as an efficient method to
      effectively and specifically silence gene expression in a vast variety of
      mammalian cells. shRNA expression is routinely driven by a RNA polymerase III
      promoter, most often by the U6 promoter. Here we demonstrate that U6 promoter
      activity-and consequently gene silencing success-differs significantly among
      species. MATERIALS AND METHODS: We have modified pLeGO-G, an HIV-based third
      generation lentivector, to express a 19nt shRNA sequence against the human
      transcription factor nuclear factor erythroid 2 or against its murine homologue,
      as well as an shRNA against murine JAK2, from either the human or the murine U6
      promoter. Gene silencing efficiency was analyzed in a human erythroleukemic cell
      line, in primary human CD34(+) cells, as well as in a murine erythroleukemic cell
      line and in primary murine bone marrow. RESULTS: ShRNA expression from the human
      U6 promoter resulted in a fourfold increase in knockdown efficiency compared to
      expression from the murine U6 promoter in both human and murine cells.
      CONCLUSIONS: The U6 promoter constitutes an important determinant for efficient
      gene silencing by shRNAs.

PMID- 20685235
TI  - Application of PAMPA-models to predict BBB permeability including efflux ratio,
      plasma protein binding and physicochemical parameters.
AB  - This study examines whether algorithms to predict brain penetration of 88 drug
      candidates could benefit from inclusion of PAMPA data such as P(eff), flux and
      membrane retention. Specifically the ability to fit experimentally derived LogBB
      data with PAMPA information and compound related physicochemical and structural
      parameters was assessed. Collected data were analyzed by partial least square
      analysis and various regression models for LogBB. Four PAMPA methodologies were
      evaluated in this study including: (1) a PAMPA-BLM (black lipid membrane) model,
      (2) a PAMPA-DS (double sink) model, (3) a PAMPA-BBB (blood-brain barrier) model
      and (4) a PAMPA-BBB-UWL (unstirred water layer). Additionally, plasma protein
      binding (PPB) experiments and a Caco-2 assay were performed to determine the
      unbound fraction in plasma and the efflux ratio, respectively, for subsets of the
      selected compounds. This information was combined with the obtained PAMPA data in
      an effort to improve the predictions of LogBB. Taken in aggregate, the results
      presented, suggest that the PAMPA-BLM parameters are the most important
      contributors to predict the LogBB. The optimized multiple linear regression (MLR)
      relationship including the PAMPA-BLM properties demonstrated a slightly improved
      prediction compared to the model without the PAMPA-BLM parameters. Including the
      plasma protein binding of 15 compounds resulted in a significantly improved PAMPA
      BLM prediction of LogBB, while integrating the efflux ratio with PAMPA-BLM or
      PAMPA-BBB P(eff) values, resulted in improved classification of brain permeable
      [BBB+(LogBB>/=0)] and impermeable [BBB-(LogBB<0)] compounds.

PMID- 20685234
TI  - KIT polymorphisms and mutations determine responses of neoplastic mast cells to
      bafetinib (INNO-406).
AB  - OBJECTIVE: Advanced systemic mastocytosis (SM) is characterized by uncontrolled
      growth of neoplastic mast cells (MC) and drug resistance. The tyrosine kinase
      receptor KIT is often mutated and activated and thus contributes to malignant
      growth of MC. Therefore, KIT-targeting drugs are currently tested for their
      ability to block growth of malignant MC. MATERIALS AND METHODS: We determined the
      effects of the multikinase inhibitor INNO-406 (bafetinib) on primary neoplastic
      MC, the canine mastocytoma cell line C2, the human MC leukemia cell line HMC-1.1
      bearing the KIT mutant V560G, and HMC-1.2 cells harboring KIT V560G and KIT
      D816V. RESULTS: INNO-406 was found to inhibit proliferation in HMC-1.1 cells
      (IC(50): 30-40 nM), but not in HMC-1.2 cells or primary neoplastic cells in
      patients with KIT D816V-positive SM. In canines, growth-inhibitory effects of
      INNO-406 were seen in C2 cells (IC(50): 50-100 nM) exhibiting a KIT exon 11
      internal tandem-duplication and in primary neoplastic MC harboring wild-type exon
      11, whereas no effects were seen in MC exhibiting a polymorphism at amino acid
      581 in exon 11. INNO-406 was found to block KIT phosphorylation and expression in
      HMC-1.1 cells and C2 cells, but not in HMC-1.2 cells, whereas Lyn-phosphorylation
      was blocked by INNO-406 in all types of MC. CONCLUSIONS: In neoplastic MC, the
      major target of INNO-406 appears to be KIT. Drug responses may depend on the
      presence and type of KIT mutation. In human MC, the KIT D816V mutant introduces
      resistance, and in canine mastocytomas, an exon 11 polymorphism may be indicative
      of resistance against INNO-406.

PMID- 20685236
TI  - Fixed artesunate-amodiaquine combined pre-formulation study for the treatment of
      malaria.
AB  - Artemisinin-based combination therapies, including artesunate (AS)+amodiaquine
      (AQ), are the currently recommended first-line treatment of uncomplicated
      falciparum malaria. Fixed-dose co-formulations offer logistic and adherence
      advantages. This paper reports the initial research phase of the pre-development
      process of an AS-AQ formulation, further developed by the Drug for Neglected
      Diseases Initiative (DNDi). Results demonstrate that AS and AQ are not
      compatible, and AS degradation is related to three main parameters: water content
      (>1%), elevated temperature (80 degrees C in dry condition) and possibly the 4
      aminoquinoline moiety. Furthermore, AS and AQ incompatibility led to AS
      degradation and pharmaco-technical changes in classical wet granulation tablets.
      Both active principles are stable as dry powders. These investigations led to
      further development of various co-formulations, including the bilayer tablet
      currently on the market.

PMID- 20685242
TI  - The biodiversity of beneficial microbe-host mutualism: the case of rhizobia.
AB  - Symbiotic nitrogen fixation is the main route for sustainable input of nitrogen
      into ecosystems. Nitrogen fixation in agriculture can be improved by inoculation
      of legume crops with suitable rhizobia. Knowledge of the biodiversity of rhizobia
      and of local populations is important for the design of successful inoculation
      strategies. Soybeans are major nitrogen-fixing crops in many parts of the world.
      Bradyrhizobial inoculants for soybean are very diverse, yet classification and
      characterization of strains have long been difficult. Recent genetic
      characterization methods permit more reliable identification and will improve our
      knowledge of local populations. Forage legumes form another group of
      agronomically important legumes. Research and extension policies valorizing
      rhizobial germplasm diversity and preservation, farmer training for proper
      inoculant use and legal enforcement of commercial inoculant quality have proved a
      successful approach to promoting the use of forage legumes while enhancing
      biological N(2) fixation. It is worth noting that taxonomically important strains
      may not necessarily be important reference strains for other uses such as legume
      inoculation and genomics due to specialization of the different fields. This
      article points out both current knowledge and gaps remaining to be filled for
      further interaction and improvement of a rhizobial commons.

PMID- 20685243
TI  - Alteration in auditory function during the ovarian cycle.
AB  - This study investigates whether physiological variations in ovarian hormones
      during the ovarian cycle (OC) are associated with changes in auditory function.
      Sixteen women with normal hearing underwent auditory tests and simultaneous
      measurements of the hormone levels four times during OC. The auditory tests
      included recording of otoacoustic emissions (OAEs), the medial olivocochlear
      (MOC) suppression and auditory brainstem responses (ABRs). The OC was defined by
      oestradiol and progesterone serum levels and menstrual cycle dating. A
      significant spontaneous OAE frequency shift [F(3,114.6)=15.8, p<0.001], with the
      greatest shift in the late follicular phase (highest oestrogen levels), was
      observed. Transient evoked OAE levels showed a consistent tendency in an increase
      in all frequency bands in the late follicular/early luteal stage and a decrease
      in the late follicular stage; TEOAE inter-session comparison indicated very small
      statistical differences. The MOC suppression changed significantly during OC
      [F(3,33.8)=3.2, p=0.036], with significant inter-session difference, lower in
      session 2 than in session 1 (p=0.019) and lower in session 4 than in session 1
      (p=0.007). The ABR wave V absolute latency changed significantly during OC
      [F(3,33)=3.3, p=0.03], longer in the late follicular phase. There was also a
      significant positive correlation of TEOAEs and ABR (wave V latency and III-V
      interval) and significant negative correlation of MOC suppression with oestradiol
      levels in the follicular phase. The results of this study reflect very small
      changes in auditory function during OC, and they are suggestive of an increased
      hearing sensitivity around the time of ovulation.

PMID- 20685244
TI  - Triadic synaptic interactions of large corticothalamic terminals in non-lemniscal
      thalamic nuclei of the cat auditory system.
AB  - Large corticothalamic (CT) terminals, presumed to originate from cortical layer 5
      pyramidal cells, are distributed predominantly in non-specific thalamic nuclei in
      mammals. In the auditory system, little is known about whether these CT
      projections participate in the synaptic aggregation referred to as the triad. We
      studied synaptic interactions of these terminals with neuronal elements in one of
      the auditory non-lemniscal thalamic nuclei, the dorsal nucleus of the medial
      geniculate complex (MGC), in cats. After injections of an anterograde tracer in
      the primary auditory cortex, areas containing labeled large terminals were
      examined using an electron microscope. It was revealed that a fraction of large
      CT terminals participated in complicated synaptic arrangements: labeled terminals
      making synaptic contacts with vesicle-free dendrites, probably of thalamic
      principal neurons, and/or vesicle-filled neuronal profiles, probably of
      presynaptic dendrites (PSDs) of interneurons. In reconstructions or even in
      single sections, we found that these synaptic connections participated in triadic
      arrangements. Thus, PSDs postsynaptic to the labeled CT terminals were in turn
      presynaptic to the vesicle-free dendrites.

PMID- 20685246
TI  - Feasibility and safety of adoptive immunotherapy with CIK cells after cord blood
      transplantation.
AB  - Five patients with aggressive acute leukemias who had relapsed after cord blood
      transplantation were treated with cord blood derived cytokine-induced killer
      (CIK) cells. These were obtained by ex vivo expansion, using as starting material
      the washouts of the cord blood units, left over at the end of the transplant. We
      did not observe any acute or delayed adverse event, and observed 1 partial
      response in 1 patient concomitantly with the development of acute grade III graft
      versus-host disease (GVHD). These observations show the relatively low toxicity
      of cord blood-derived CIK cells and, more importantly, the feasibility of this
      immunotherapy program for patients who could not otherwise benefit from donor
      lymphocyte infusions.

PMID- 20685247
TI  - Nitrile hydratases (NHases): at the interface of academia and industry.
AB  - Nitrile hydratase (NHase, EC 4.2.1.84) is one of the key enzymes of nitrile
      metabolism in a large number of microbes that catalyses the hydration of nitriles
      to corresponding amides, and has been successfully adopted in chemical industry
      for production of acrylamide, nicotinamide and 5-cyanovaleramide. However, NHase
      is still under active consideration of enzymologists to expand its potential for
      synthesis of various amides. Most of the NHases have been reported for their
      limited substrates acceptability, low enantioselectivity and thermostability and
      therefore a considerable improvement is required for developing as robust
      biocatalyst for synthesis of a range of organic amides. Studies on biochemical
      properties, gene configuration, active-site chemical models and site-directed
      mutagenesis have given the insight into the structural and functional
      characteristics of NHase. Keeping in view, the present review critically
      describes the available information on natural sources (based on activity and
      phylogenetic analysis), biochemical properties, catalysis-structure relationship,
      molecular expression and potential applications of this enzyme.

PMID- 20685248
TI  - Midostaurin (PKC412) modulates differentiation and maturation of human myeloid
      dendritic cells.
AB  - Midostaurin, a tyrosine kinase inhibitor, has been shown efficacy against acute
      myeloid leukemia and various other malignancies in clinical trials. Prior studies
      indicate midostaurin affects the function of immune cells such as lymphocytes and
      macrophages. To understand the effect of midostaurin on human myeloid dendritic
      cells (DCs), we conducted an ex vivo study using immature DCs differentiated from
      CD14(+) monocytes and further maturated using lipopolysaccharide. Addition of
      midostaurin to a culture of starting CD14(+) monocytes markedly and dose
      dependently reduced DC recovery. Mature DCs differentiating in the presence of
      midostaurin had fewer, shorter cell projections than those differentiating in the
      absence of midostaurin. Changes in morphological features characteristic of
      apoptotic cells were also evident. Moreover, midostaurin affected DC
      differentiation and maturation patterns; CD83 expression levels decreased,
      whereas CD14 and CD80 expressions increased. Additionally, DCs derived in the
      presence of midostaurin possessed a lower endocytotic capacity and less
      allostimulatory activity on naive CD4(+)CD45(+)RA(+) T cell proliferation than
      those derived in its absence, suggesting that midostaurin redirects DC
      differentiation toward a less mature stage and that this effect is not solely due
      to its cytotoxicity. Whether this effect underlies immune suppression or
      tolerance to disease treatments with unwanted immune reactions needs further
      evaluation.

PMID- 20685249
TI  - Effects of alcohol-drinking behaviour and ADH1B and ALDH2 polymorphisms on basal
      DNA damage in human mononuclear cells as determined by the comet assay.
AB  - The aim of this study was to investigate the effects of alcohol drinking and
      ADH1B and ALDH2 polymorphisms on basal DNA damage (measured by the alkaline comet
      assay) of mononuclear cells in 122 healthy Japanese workers. Our results showed
      that drinking frequency had a significant impact on the tail moment (TM) value,
      with the highest TM value observed in habitual drinkers. The presence of the
      ADH1B*2 or ALDH2*2 allele was associated with increased DNA damage in older
      habitual drinkers. Furthermore, habitual drinkers with a combined genotype of
      ADH1B*2/*2 and ALDH2*1/*2 demonstrated a significantly higher TM value than other
      groups. Moreover, the combination of drinking and smoking has a combined effect
      on DNA damage. Multiple regression analysis revealed that drinking frequency,
      smoking status, and ALDH2 polymorphisms significantly influence basal TM value,
      suggesting that these are important variables affecting individual basal DNA
      damage.

PMID- 20685250
TI  - Hydrogen sulfide: regulatory role on blood pressure in hyperhomocysteinemia.
AB  - Hyperhomocysteinemia (HHcy) is a metabolic disorder marked by an excess amount of
      the amino acid homocysteine (Hcy) in the blood stream. Hcy is a H(2)S precursor
      formed from the metabolism of methionine. Elevated Hcy levels have been
      associated with higher blood pressure. However, the precise contribution of H(2)S
      to blood pressure in HHcy is not known. In the current study, we have examined a
      novel link between H(2)S, blood pressure and HHcy. Male Sprague-Dawley rats were
      injected with PAG, NaHS, L-NAME+PAG and saline. HHcy condition was induced by
      providing methionine (1 g/kg) in drinking water for 8 weeks. After 8 weeks,
      plasma Hcy and H(2)S were measured. The treated rats were anaesthetized with a
      mixture of ketamine hydrochloride and medetomidine. Blood pressures were measured
      by intra-carotid artery catheterization and to further investigate the immediate
      effect of NO and H(2)S, exogenous drugs namely NaHS, SNP, Ach and NA were
      administered. Plasma Hcy levels were higher in HHcy groups and this group
      exhibited hypertension. We observed high blood pressure at low levels of H(2)S
      and vice versa. Endogenous H(2)S in HHcy condition facilitated a mild decrease in
      MAP (Mean Arterial Pressure). Exogenous SNP (NO donor) showed a greater pressure
      decrease in HHcy group. The underlying mechanism is yet to be exploited. High
      levels of Hcy play an important role in the pathogenesis of hypertension. The
      results suggest that both endogenous and exogenous H(2)S may play a vital role in
      regulating blood pressure in HHcy.

PMID- 20685251
TI  - Potential mechanisms of endogenous retroviral-mediated genomic instability in
      human cancer.
AB  - Malignancy results from a complex combination of genetic and epigenetic changes,
      the full effects of which are still largely unknown. Here we summarize current
      knowledge of the origin, retrotranspositional activity, epigenetic state, and
      transcription of human endogenous retroviruses (HERVs), and then discuss the
      potential effects of their deregulation in cancer. Evidence suggests that cancer
      associated epigenetic changes most likely underlie potential HERV-mediated
      effects on genome and transcriptome instability and may play a role in
      malignancy. Despite our currently limited understanding of the importance of
      HERVs or other transposable elements in cancer development, we believe that the
      emerging era of high-throughput sequencing of cancer genomes, epigenomes, and
      transcriptomes will provide unprecedented opportunities to investigate these
      roles in the future.

PMID- 20685252
TI  - Two-dimensional gel electrophoresis in proteomics: Past, present and future.
AB  - Two-dimensional gel electrophoresis has been instrumental in the birth and
      developments of proteomics, although it is no longer the exclusive separation
      tool used in the field of proteomics. In this review, a historical perspective is
      made, starting from the days where two-dimensional gels were used and the word
      proteomics did not even exist. The events that have led to the birth of
      proteomics are also recalled, ending with a description of the now well-known
      limitations of two-dimensional gels in proteomics. However, the often
      underestimated advantages of two-dimensional gels are also underlined, leading to
      a description of how and when to use two-dimensional gels for the best in a
      proteomics approach. Taking support of these advantages (robustness, resolution,
      and ability to separate entire, intact proteins), possible future applications of
      this technique in proteomics are also mentioned.

PMID- 20685255
TI  - Consensus Conference on Clinical Practice in Chronic GVHD: Second-Line Treatment
      of Chronic Graft-versus-Host Disease.
AB  - Steroid refractory chronic graft-versus-host disease (cGVHD) is associated with a
      significant morbidity and mortality. Although first-line treatment of cGVHD is
      based on controlled trials, second-line treatment is almost solely based on phase
      II trials or retrospective analyses. The consensus conference on clinical
      practice in cGVHD held in Regensburg aimed to achieve a consensus on the current
      evidence of treatment options as well as to provide guidelines for daily clinical
      practice. Treatment modalities are the use of steroids and calcineurin inhibitors
      as well as immunomodulating modalities (photopheresis, mTOR-inhibitors,
      thalidomide, hydroxychloroquine, vitamin A analogs, clofazimine), and cytostatic
      agents (mycophenolate mofetil, methotrexate, cyclophosphamide, pentostatin).
      Recent reports showed some efficacy of rituximab, alemtuzumab, and etanercept in
      selected patients. Moreover, tyrosine kinase inihibitors such as imatinib came
      into the field because of their ability to interfere with the platelet-derived
      growth factor (PDGF-R) pathway involved in fibrosis. An other treatment option is
      low-dose thoracoabdominal irradiation. Although different treatment options are
      available, the "trial-and-error system" remains the only way to identify the drug
      effective in the individual patient, and valid biomarkers are eagerly needed to
      identify the likelihood of response to a drug in advance. Moreover, the sparse
      evidence for most treatment entities indicates the urgent need for systematic
      evaluation of second-line treatment options in cGVHD.

PMID- 20685257
TI  - The changing epidemiology of vancomycin-resistant Enterococcus (VRE) bacteremia
      in allogeneic hematopoietic stem cell transplant (HSCT) recipients.
AB  - The impact of the rising prevalence of vancomycin-resistant Enterococcus (VRE)
      prior to hematopoietic stem cell transplantation (HSCT) and changes in transplant
      techniques on risk of VREB (VRE bacteremia) early after HSCT is not known. This
      is a retrospective study of 247 adult patients who underwent allogeneic HSCT in
      the years 2008 and 2009 at the Memorial Sloan-Kettering Cancer Center. Sixty
      eight of 247 (27.5%) patients were VRE colonized on pretransplant screening. VRE
      was the leading cause of bacteremia in the first 30 days after HSCT; 23 of 43
      (53.5%) patients with positive blood cultures had VRE. Only 13 (57%) of the 23
      patients with early VREB were colonized with VRE on pre-HSCT screening cultures.
      Mortality was directly attributable to VRE infection in 9% of patients with early
      VREB. VRE is emerging as the most common cause of preengraftment bacteremia in
      patients undergoing allogeneic HSCT, and is associated with substantial
      mortality. Pre-HSCT screening for VRE with stool cultures will not identify all
      patients who are at risk for VREB. The use of alternate agents with activity
      against Gram-positive bacteria for fever and neutropenia early after HSCT should
      be evaluated further in prospective studies.

PMID- 20685256
TI  - Successful engraftment with fludarabine, cyclophosphamide, and thymoglobulin
      conditioning regimen in unrelated transplantation for severe aplastic anemia: A
      phase II prospective multicenter study.
AB  - Antithymocyte globulin (ATG) has been used in severe aplastic anemia (SAA) as
      part of the conditioning regimen. Among the many kinds of ATG preparations,
      thymoglobulin had been found to be more effective for preventing graft-versus
      host disease (GVHD) and the rejection of organ transplants. After the promising
      results of our preliminary study, we conducted a phase II prospective multicenter
      clinical trial using a fludarabine (Flu), cyclophosphamide (Cy), and
      thymoglobulin conditioning regimen to allow good engraftment in patients who
      underwent unrelated transplantation for SAA. Twenty-eight patients underwent bone
      marrow (N = 15) or mobilized peripheral blood (N = 13) transplantation from HLA
      matched unrelated donors with Cy (50 mg/kg once daily intravenously (i.v.) on
      days -9, -8, -7, and -6), Flu (30 mg/m2 once daily i.v. on days -5, -4, -3, and 
      2), and thymoglobulin (2.5 mg/kg once daily i.v. on days -3, -2, and -1). Donor
      type hematologic recovery was achieved in all patients. The estimated survival
      rate (SR) was 67.9%, and all the events were treatment-related mortality (TRM),
      which included thrombotic microangiopathy (N = 2), pneumonia (N = 1), myocardiac
      infarction (N = 1), posttransplantation lymphoprolifarative disease (N = 3), and
      chronic GVHD-associated complications (N = 2). The SR of patients who received
      bone marrow (60.0%) was not different from that of patients who received
      mobilized peripheral blood (76.9%) (P = .351), but the SR of patients who
      received more than 15 units of red blood cells before transplantation (45.5%) was
      significantly lower than that of the other patients (82.4%) (P = .048). The Flu,
      Cy, and thymoglobulin conditioning regimen achieved promising results for
      successful engraftment, but the TRM was high. This study was registered at
      www.clinicaltrials.gov (NCT00737685), and now we are performing a new multicenter
      study (NCT00882323) to decrease the TRM by reducing the dose of Cy.

PMID- 20685258
TI  - High incidence of human herpes virus 6-associated encephalitis/myelitis following
      a second unrelated cord blood transplantation.
AB  - Human herpes virus (HHV)6-associated limbic encephalitis and/or myelitis is one
      of the life-threatening central nervous system complications following allogeneic
      hematopoietic stem cell transplantation (HSCT). Recent reports have shown
      significant correlations of these complications with unrelated cord blood
      transplantation (UCBT). We retrospectively analyzed 228 allogeneic HSCT
      recipients in our single institution; 13 patients (5.7%) were diagnosed with HHV6
      associated encephalitis/myelitis. This complication was documented in 8 of 51
      UCBT recipients (15.7%) and 5 of 177 recipients (2.8%) transplanted with bone
      marrow or peripheral blood stem cells, indicating a higher incidence of this
      complication occurring in UCBT recipients (P = .0005). In addition, HHV6
      associated encephalitis/myelitis occurred more frequently in recipients who
      underwent 2 or more HSCTs (7 of 59 recipients [11.9%]), compared to those who
      received only 1 HSCT (6 of 169 recipients [3.6%], P = .018). Of note, the
      incidence of this complication increased to 28.6% (6 of 21 recipients), when the
      analysis was restricted to a second or more UCBT recipients. All 13 patients
      presented preengraftment immune response prior to the onset of encephalitis. Two
      patients manifested typical symptoms at the onset of HHV6-associated
      encephalitis/myelitis, such as memory dysfunction, disorientation, and
      consciousness disturbance. However, 4 patients presented only with dysesthesia
      and pruritus, described as typical manifestations of patients with calcineurin
      inhibitor-induced pain syndrome (CIPS), and the remaining 7 showed both symptoms,
      indicating that CIPS-like symptoms might be manifestations of HHV6-associated
      myelitis. Thus, physicians should be alert to this rare but often fatal
      complication, particularly for those who receive 2 or more HSCTs using UCB.

PMID- 20685259
TI  - Conditioning with treosulfan and fludarabine followed by allogeneic hematopoietic
      cell transplantation for high-risk hematologic malignancies.
AB  - In this prospective study 60 patients of median age 46 (range: 5-60 years), with
      acute myelogenous leukemia (AML; n = 44), acute lymphoblastic leukemia (ALL; n =
      3), or myelodysplastic syndrome (MDS; n = 13) were conditioned for allogeneic
      hematopoietic cell transplantation with a treosulfan/fludarabine (Flu)
      combination. Most patients were considered at high risk for relapse or nonrelapse
      mortality (NRM). Patients received intravenous treosulfan, 12 g/m(2)/day (n = 5)
      or 14 g/m(2)/day (n = 55) on days -6 to -4, and Flu (30 mg/m(2)/day) on days -6
      to -2, followed by infusion of marrow (n = 7) or peripheral blood stem cells (n =
      53) from HLA-identical siblings (n = 30) or unrelated donors (n = 30). All
      patients engrafted. NRM was 5% at day 100, and 8% at 2 years. With a median
      follow-up of 22 months, the 2-year relapse-free survival (RFS) for all patients
      was 58% and 88% for patients without high-risk cytogenetics. The 2-year
      cumulative incidence of relapse was 33% (15% for patients with MDS, 34% for AML
      in first remission, 50% for AML or ALL beyond first remission and 63% for AML in
      refractory relapse). Thus, a treosulfan/Flu regimen was well tolerated and
      yielded encouraging survival and disease control with minimal NRM. Further trials
      are warranted to compare treosulfan/Flu to other widely used regimens, and to
      study the impact of using this regimen in more narrowly defined groups of
      patients.

PMID- 20685260
TI  - Impact of recipient statin treatment on graft-versus-host disease after
      allogeneic hematopoietic cell transplantation.
AB  - We retrospectively analyzed outcomes among 1206 patients with hematologic
      malignancies who had hematopoietic cell transplantation (HCT) from HLA-identical
      siblings (n = 630) or HLA-matched unrelated donors (n = 576) at a single
      institution between 2001 and 2007 for a correlation between recipient statin use
      and risk of graft-versus-host disease (GVHD). Among recipients with cyclosporine
      based postgrafting immunosuppression (n = 821), statin use at the time of
      transplant (6%) was associated with a decreased risk of extensive chronic GVHD
      (cGVHD) (multivariate hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.4
      1.0; P = .05) and an increased risk of recurrent malignancy (HR, 1.75; 95% CI,
      1.0-3.0; P = .04). Recipient statin use, however, had no apparent impact on the
      risks of cGVHD and recurrent malignancy among recipients given tacrolimus-based
      immunosuppression (n = 385; 8% statin treated). Risks of acute GVHD, nonrelapse
      mortality, and overall mortality were not significantly affected by recipient
      statin use. Hence, recipient statin treatment at the time of allogeneic HCT may
      decrease the risk of cGVHD in patients with cyclosporine-based immunosuppression,
      but at the expense of a compromised graft-versus-tumor effect.

PMID- 20685261
TI  - Protective effect of chloral hydrate against lipopolysaccharide/D-galactosamine
      induced acute lethal liver injury and zymosan-induced peritonitis in mice.
AB  - In recent years, certain anesthetics have been shown to have protective effects
      against acute inflammation in experimental animals, an observation that may yield
      new options for adjunctive treatment of acute inflammation. In this study, we
      investigated the effects of chloral hydrate (CH) on the acute inflammatory
      response in BALB/c mice using lipopolysaccharide/D-galactosamine (LPS/D-GalN)
      induced acute lethal liver injury and zymosan A-induced peritonitis models. The
      survival of mice following LPS/D-GalN treatment was significantly improved by a
      single injection with chloral hydrate, which could be administered simultaneously
      or as late as 3h after challenge with LPS/D-GalN; liver injury was also
      attenuated. A sharp rise in serum levels of MCP-1, IL-6 and TNF-alpha was
      attenuated or delayed after chloral hydrate treatment. Furthermore, the mechanism
      by which chlorate hydrate inhibits inflammation was associated with an attenuated
      increase in nuclear factor kappaappaB (NF-kappaB) activity in NF-kappaB-RE-luc
      mice upon LPS/D-GalN treatment. In mice with acute peritonitis, leukocyte number
      and protein concentration in peritoneal exudates peaked with a 16h lag, and serum
      levels of MCP-1, IL-6 and TNF-alpha were significantly lower at certain time
      points in the chloral hydrate-treated group compared to those in the normal
      saline (NS)-treated control group. In addition, chloral hydrate treatment in
      vitro attenuated the upregulation of TNF-alpha and IL-6 by peritoneal macrophages
      and NF-kappaB activity in RAW264.7 cells stimulated with LPS, suggesting that
      monocytes/macrophages may be a target of chloral hydrate. These results indicate
      that chloral hydrate has a protective effect against LPS/D-GalN-induced acute
      lethal liver injury in mice, which may be associated with an inhibition of NF
      kappaB activity and delays in proinflammatory cytokine production. However, this
      phenomenon was not associated with levels of serum corticosterone. Chloral
      hydrate also attenuated the inflammatory response in zymosan A-induced acute
      peritonitis, a model of mild inflammation. In conclusion, treatment with only a
      single injection of chloral hydrate could significantly attenuate acute
      inflammation in mice treated with LPS/D-GalN and zymosan A. These effects are
      also likely associated with the inhibition of NF-kappaB activity.

PMID- 20685262
TI  - Thermal sensitivity in the elderly: a review.
AB  - Aging is associated with a progressive decrease in thermal perception, as
      revealed by increased thermal detection thresholds in the elderly. This reduction
      in thermosensitivity follows a distal-proximal pattern, with more pronounced
      decrements observed in the limbs and in the perception of warmth vs. cold. The
      main underlying causes of this seem to be aging of the skin and subsequent
      reductions in thermoreceptor density and superficial skin blood flow. However,
      the results from some animal studies also suggest that changes in the peripheral
      nerve system, particularly fiber loss and decreased conduction velocity, may also
      be involved. In this paper, we review age-related changes in the thermal
      sensitivity of humans, their underlying mechanisms, and the strengths and
      limitations of some of the methodologies used to assess these changes.

PMID- 20685272
TI  - Analysis of MTMR1 expression and correlation with muscle pathological features in
      juvenile/adult onset myotonic dystrophy type 1 (DM1) and in myotonic dystrophy
      type 2 (DM2).
AB  - Among genes abnormally expressed in myotonic dystrophy type1 (DM1), the
      myotubularin-related 1 gene (MTMR1) was related to impaired muscle
      differentiation. Therefore, we analyzed MTMR1 expression in correlation with CUG
      binding protein1 (CUG-BP1) and muscleblind-like1 protein (MBNL1) steady-state
      levels and with morphological features in muscle tissues from DM1 and myotonic
      dystrophy type 2 (DM2) patients. Semi-quantitative RT-PCR for MTMR1 was done on
      muscle biopsies and primary muscle cultures. The presence of impaired muscle
      fiber maturation was evaluated using immunochemistry for neural cell adhesion
      molecule (NCAM), Vimentin and neonatal myosin heavy chain. CUG-BP1 and MBNL1
      steady-state levels were estimated by Western blot. RNA-fluorescence in situ
      hybridization combined with immunochemistry for CUG-BP1, MBNL1 and NCAM were
      performed on serial muscle sections. An aberrant splicing of MTMR1 and a
      significant amount of NCAM-positive myofibers were detected in DM1 and DM2 muscle
      biopsies; these alterations correlated with DNA repeat expansion size only in
      DM1. CUG-BP1 levels were increased only in DM1 muscles, while MBNL1 levels were
      similar among DM1, DM2 and controls. Normal and NCAM-positive myofibers displayed
      no differences either in the amount of ribonuclear foci and the intracellular
      distribution of MBNL1 and CUG-BP1. In conclusion, an aberrant MTMR1 expression
      and signs of altered myofiber maturation were documented in both DM1 and in DM2
      muscle tissues. The more severe dysregulation of MTMR1 expression in DM1 versus
      DM2, along with increased CUG-BP1 levels only in DM1 tissues, suggests that the
      mutual antagonism between MBNL1 and CUG-BP1 on alternative splicing is more
      unbalanced in DM1.

PMID- 20685273
TI  - Core histone H2A ubiquitylation and transcriptional regulation.
AB  - Diverse histone modifications, such as acetylation, methylation and
      ubiquitylation have been linked to the regulation of cellular activities such as
      transcription, repair and replication. The mechanisms by which histone
      modifications contribute to the transcription process are not fully understood;
      however increasing evidence suggests that they work together in the form of a
      histone code to regulate the recruitment of chromatin-modulating factors [1-3].
      Histone ubiquitylation has been found to be an important chromatin modification
      with roles in trans-histone modification and transcriptional regulation. In the
      past several years, there has been dramatic progress in the identification of
      factors that control ubiquitin attachment to the histone. Recent advances
      concerning core histone H2A ubiquitylation and transcriptional regulation will be
      reviewed and the cellular functions of these histone modifications will be
      discussed.

PMID- 20685274
TI  - Rapid identification of lymnaeid snails and their infection with Fasciola
      gigantica in Thailand.
AB  - Freshwater snails of the family Lymnaeidae are the intermediate hosts of the
      liver fluke Fasciola worldwide. While distinct species have been identified at
      the molecular level in other parts of the world such data have not been published
      for Thailand. In this study we collected Lymnaeidae from different localities
      across Thailand and analyzed their 16S rDNA sequences as a molecular signature
      for classification. In addition to the ubiquitous Radix rubiginosa, we have
      confirmed the presence of Austropeplea viridis and Radix swinhoei, for the latter
      of which the ribosomal rDNA sequences are reported for the first time, in North
      Thailand. Based on the obtained 16S rDNA data three primer pairs were designed
      that allowed rapid identification of these snail species by PCR. To determine
      their infection status, PCR primers for F.gigantica cathepsin L were used in
      parallel with the snail 16S rDNA species-specific primers in multiplex PCR
      analyses. Western blot analysis of total snail protein with a monoclonal anti
      F.gigantica cathepsin L antibody confirmed positive cathepsin L PCR results. The
      developed diagnostic PCR will be of use in risk assessment for transmission of
      fascioliasis in Thailand.

PMID- 20685276
TI  - Crystal Structure of the 2-Oxoglutarate- and Fe(II)-Dependent Lysyl Hydroxylase
      JMJD6.
AB  - Lysyl and prolyl hydroxylations are well-known post-translational modifications
      to animal and plant proteins with extracellular roles. More recent work has
      indicated that the hydroxylation of intracellular animal proteins may be common.
      JMJD6 catalyses the iron- and 2-oxoglutarate-dependent hydroxylation of lysyl
      residues in arginine-serine-rich domains of RNA-splicing-related proteins. We
      report crystallographic studies on the catalytic domain of JMJD6 in complex with
      Ni(II) substituting for Fe(II). Together with mutational studies, the structural
      data suggest how JMJD6 binds its lysyl residues such that it can catalyse C-5
      hydroxylation rather than N(varepsilon)-demethylation, as for analogous enzymes.

PMID- 20685275
TI  - Morbidity and mortality among older individuals with undiagnosed celiac disease.
AB  - BACKGROUND & AIMS: Outcomes of undiagnosed celiac disease (CD) are unclear. We
      evaluated the morbidity and mortality of undiagnosed CD in a population-based
      sample of individuals 50 years of age and older. METHODS: Stored sera from a
      population-based sample of 16,886 Olmsted County, Minnesota, residents 50 years
      of age and older were tested for CD based on analysis of tissue transglutaminase
      and endomysial antibodies. A nested case-control study compared serologically
      defined subjects with CD with age- and sex-matched, seronegative controls.
      Medical records were reviewed for comorbid conditions. RESULTS: We identified 129
      (0.8%) subjects with undiagnosed CD in a cohort of 16,847 older adults. A total
      of 127 undiagnosed cases (49% men; median age, 63.0 y) and 254 matched controls
      were included in a systematic evaluation for more than 100 potentially coexisting
      conditions. Subjects with undiagnosed CD had increased rates of osteoporosis and
      hypothyroidism, as well as lower body mass index and levels of cholesterol and
      ferritin. Overall survival was not associated with CD status. During a median
      follow-up period of 10.3 years after serum samples were collected, 20 cases but
      no controls were diagnosed with CD (15.2% Kaplan-Meier estimate at 10 years).
      CONCLUSIONS: With the exception of reduced bone health, older adults with
      undiagnosed CD had limited comorbidity and no increase in mortality compared with
      controls. Some subjects were diagnosed with CD within a decade of serum
      collection, indicating that although most cases of undiagnosed CD are clinically
      silent, some result in symptoms. Undiagnosed CD can confer benefits and
      liabilities to older individuals.

PMID- 20685279
TI  - A concise synthesis of beta-sitosterol and other phytosterols.
AB  - A convenient synthesis of sidechain-modified phytosterols is achieved via a
      temporary masking of the stigmasterol 5,6-alkene as an epoxide. Following
      performance of the desired modification, the alkene is regenerated through a mild
      deoxygenation. The approach is applied to the syntheses of beta-sitosterol and
      campesterol acetate, and suggests a facile route to the (Z)-isomers of Delta(22
      23) phytosterols.

PMID- 20685284
TI  - Protective effect of beta-casomorphin-7 on type 1 diabetes rats induced with
      streptozotocin.
AB  - The present study was aimed to investigate the possible effects of beta
      casomorphin-7, against hyperglycemia and free radical-mediated oxidative stress
      in streptozotocin-induced diabetic rats by assaying the blood glucose level and
      the activity of plasma enzymatic antioxidants, such as superoxide dismutase
      (SOD), catalase and glutathione peroxidase (GSH-Px). A significant increase in
      the levels of both blood glucose and oxidative stress with a predominant decrease
      in antioxidant status was observed in the diabetic rats when compared to control
      rats. After 15 days oral administration of beta-casomorphin-7 (7.5 x 10(-8)
      mol/day), the elevated blood glucose level was reduced. Oral administration of
      beta-CM-7 to diabetic rats showed an increase in the level of plasma insulin, the
      elevated plasma glucagon level was markedly reduced by the oral administration of
      beta-CM-7. Oral administration of beta-CM-7 to the diabetic group of rats also
      showed a significant elevation in the activity of SOD and catalase. Thus, the
      results of the present study suggest that beta-casomorphin-7 can protect rats
      from hyperglycemia and free radical-mediated oxidative stress in diabetic rats.

PMID- 20685285
TI  - Molecular cloning and characterization of two putative appetite regulators in
      winter flounder (Pleuronectes americanus): preprothyrotropin-releasing hormone
      (TRH) and preproorexin (OX).
AB  - cDNAs encoding for preproTRH and preproorexin were cloned in winter flounder, a
      species that undergoes a period of natural fasting during the winter. For both
      peptides, the deduced amino acid structure of the hormone precursor shows 30-70%
      similarities with their homologs in other fish species. RT-PCR studies show that
      these peptides are present not only in the brain, but also in several peripheral
      tissues, including gastrointestinal tract and testes. Fasting induced increases
      in both preproorexin and preproTRH expressions in the hypothalamus, but did not
      affect their expression levels in the telencephalon/preoptic area. In addition,
      the mRNA expressions of both preproorexin and preproTRH were higher in the winter
      than in the summer in both hypothalamus and telencephalon/preoptic area. Our
      results suggest that orexin and thyrotropin-releasing hormone (TRH) might have a
      role in the seasonal regulation of food intake in winter flounder.

PMID- 20685286
TI  - Chemical-specific screening criteria for interpretation of biomonitoring data for
      volatile organic compounds (VOCs)--application of steady-state PBPK model
      solutions.
AB  - The National Health and Nutrition Examination Survey (NHANES) generates
      population-representative biomonitoring data for many chemicals including
      volatile organic compounds (VOCs) in blood. However, no health or risk-based
      screening values are available to evaluate these data from a health safety
      perspective or to use in prioritizing among chemicals for possible risk
      management actions. We gathered existing risk assessment-based chronic exposure
      reference values such as reference doses (RfDs), reference concentrations (RfCs),
      tolerable daily intakes (TDIs), cancer slope factors, etc. and key
      pharmacokinetic model parameters for 47 VOCs. Using steady-state solutions to a
      generic physiologically-based pharmacokinetic (PBPK) model structure, we
      estimated chemical-specific steady-state venous blood concentrations across
      chemicals associated with unit oral and inhalation exposure rates and with
      chronic exposure at the identified exposure reference values. The geometric means
      of the slopes relating modeled steady-state blood concentrations to steady-state
      exposure to a unit oral dose or unit inhalation concentration among 38 compounds
      with available pharmacokinetic parameters were 12.0 microg/L per mg/kg-d
      (geometric standard deviation [GSD] of 3.2) and 3.2 microg/L per mg/m(3)
      (GSD=1.7), respectively. Chemical-specific blood concentration screening values
      based on non-cancer reference values for both oral and inhalation exposure range
      from 0.0005 to 100 microg/L; blood concentrations associated with cancer risk
      specific doses at the 1E-05 risk level ranged from 5E-06 to 6E-02 microg/L. The
      distribution of modeled steady-state blood concentrations associated with unit
      exposure levels across VOCs may provide a basis for estimating blood
      concentration screening values for VOCs that lack chemical-specific
      pharmacokinetic data. The screening blood concentrations presented here provide a
      tool for risk assessment-based evaluation of population biomonitoring data for
      VOCs and are most appropriately applied to central tendency estimates for such
      datasets.

PMID- 20685287
TI  - Fifty-two week chronic toxicity of enzymatically decomposed rutin in Wistar rats.
AB  - The chronic toxicity of enzymatically decomposed rutin, which consists mainly of
      isoquercitrin, was evaluated in male and female Wistar rats with dietary
      administration at concentrations of 0%, 0.04%, 0.2%, 1% and 5% for 52 weeks. No
      toxicological findings were found in the mortality, body weights, food
      consumption, hematology, clinical biochemistry or organ weights in either sex.
      Obvious clinical signs were chromaturia that could be attributed to the color of
      test substance in the 5% groups of both sexes. Coloration of the urine collected
      over 24h in the 1% and 5% groups of both sexes was noted. Increased daily urinary
      calcium excretion was observed in the 5% groups of both sexes and an increase in
      urinary calcium concentration was observed in the male 5% group. On
      histopathological examination, incidences of mineralization, inflammatory cell
      debris, inflammatory cell infiltration and/or transitional cell hyperplasia in
      the renal pelvis were increased in the 5% male group, whereas treated females
      showed no apparent difference in these incidences. Based on the above findings,
      the no observed adverse effect level (NOAEL) was estimated to be 1% in both sexes
      (542.4 mg/kg body weight/day for males and 674.0mg/kg body--weight/day for
      females).

PMID- 20685289
TI  - Listeria monocytogenes (delta-actA mutant) infection in tumor necrosis factor
      receptor p55-deficient neonatal mice.
AB  - Using TNF receptor 1 knock out (TNFR1KO) mice, we investigated the role played by
      TNFR1 in immune regulation during neonatal listeriosis. Induction of protective
      immune response in wild type pups resulted in the prompt control of infection
      with an attenuated DeltaactA mutant Listeria monocytogenes, accompanied by
      enhanced hepatic expression of mRNA for IFN-gamma, TNF-alpha, and IL-10.
      Conversely, the lack of TNFR1 signalling in TNFR1KO neonatal mice resulted in
      substantial changes in the profile of inflammatory mediators and ultimately fatal
      outcome of the infected pups. Despite remarkable increase in indoleamine 2, 3
      dioxygenase (IDO) and inducible nitric oxide synthase (iNOS) mRNA detected in the
      liver of TNFR1KO mice, bacterial proliferation was unrestrained. Increased mRNA
      expression of IDO, iNOS, TNF-alpha, IFN-gamma, MCP-1, and MIP-1alpha was found in
      the spleens of infected KO mice, and in the brains mRNA encoding iNOS, IDO, IFN
      gamma, IL-12p40, IL-10, and RANTES was also upregulated. Large necrotic lesions
      consisting of granulocytes and macrophages were scattered throughout the liver of
      these mice. TNFR1KO neonates were unable to clear neutrophils and switch from the
      innate immune response to a specific reaction mediated by T cells. These results
      prove that TNF-alpha signalling is crucial and irreplaceable in antilisterial
      protection during the neonatal period.

PMID- 20685288
TI  - The dominance of inhibition in the inferior colliculus.
AB  - Almost all of the processing that occurs in the various lower auditory nuclei
      converges upon a common target in the central nucleus of the inferior colliculus
      (ICc) thus making the ICc the nexus of the auditory system. A variety of new
      response properties are formed in the ICc through the interactions among the
      excitatory and inhibitory inputs that converge upon it. Here we review studies
      that illustrate the dominant role inhibition plays in the ICc. We begin by
      reviewing studies of tuning curves and show how inhibition shapes the variety of
      tuning curves in the ICc through sideband inhibition. We then show how inhibition
      shapes selective response properties for complex signals, focusing on selectivity
      for the sweep direction of frequency modulations (FM). In the final section we
      consider results from in vivo whole-cell recordings that show how parameters of
      the incoming excitation and inhibition interact to shape directional selectivity.
      We show that post-synaptic potentials (PSPs) evoked by different signals can be
      similar but evoke markedly different spike-counts. In these cases, spike
      threshold acts as a non-linear amplifier that converts small differences in PSPs
      into large differences in spike output. Such differences between the inputs to a
      cell compared to the outputs from the same cell suggest that highly selective
      discharge properties can be created by only minor adjustments in the synaptic
      strengths evoked by one or both signals. These findings also suggest that
      plasticity of response features may be achieved with far less modifications in
      circuitry than previously supposed.

PMID- 20685290
TI  - Lack of aggression and anxiolytic-like behavior in TNF receptor (TNF-R1 and TNF
      R2) deficient mice.
AB  - The mechanisms underlying violence and aggression and its control remain poorly
      understood. Using the resident-intruder paradigm, we have discovered that
      resident mice with combined deletion of TNF receptor type 1 (TNF-R1) and type 2
      (TNF-R2) genes show a striking absence of aggressive behavior, which includes
      fighting, sideways postures, and tail rattling. In parallel, resident TNF-R1 and
      TNF-R2 knockout mice show an increase in non-aggressive exploration of the
      intruder mice. Given the relationship between aggression and anxiety, we also
      measured anxiety-related behavior, as reflected by performance in the Open Field
      and the Light-Dark Choice Test. Compared with wild type mice, TNF-R1 and TNF-R2
      deficient mice spent significantly more time and showed increased movement in the
      center of the Open Field and in the illuminated compartment of the light-dark
      box, suggesting an anxiolytic-like profile. Together, these data show that
      combined deletion of TNF-R1 and TNF-R2 results in a striking absence of
      aggressive behavior, an increase in non-aggressive exploration, and anxiolytic
      like effects. These findings identify potent roles for TNF in regulating
      aggression and anxiety-related behavior, and suggest that TNF receptor signaling
      tonically modulates activity in brain regions underlying these behaviors.

PMID- 20685291
TI  - Phylogeny and species boundaries of the endemic species complex, Eliurus antsingy
      and E. carletoni (Rodentia: Muroidea: Nesomyidae), in Madagascar using
      mitochondrial and nuclear DNA sequence data.
AB  - Current understanding of the taxonomy and species relationships within the genus
      Eliurus, a member of the endemic Malagasy rodent subfamily Nesomyinae, is largely
      based on morphological characters. Little has been published about the historical
      biogeography and diversification factors in members of this genus. Here we
      examined, using molecular data, the evolutionary relationships, and species
      boundaries within a species complex of Eliurus and the role of rivers in their
      evolution. Specifically, we tested the hypothesized monophyly of E. antsingy
      (west) and the recently described E. carletoni (north) using two mitochondrial
      genes, cytochrome b, the control region, and a nuclear marker, the Interstitial
      Retinol Binding Protein (IRBP). We also assessed the species boundaries of E.
      carletoni and examined phylogeographic patterns using two mitochondrial markers
      and an extensive geographic sampling. Molecular data show that members of the E.
      antsingy and E. carletoni complex together form a monophyletic group. Although
      samples provisionally assigned to E. carletoni based on morphological characters
      from different sites in northern Madagascar cluster in three separate
      phylogroups, they are monophyletic and assignable to this species. Rivers do not
      act as strict barriers to dispersal in E. carletoni. The demonstrated monophyly
      of both E. antsingy and E. carletoni contributes to the amounting evidence for a
      biogeographic link between the north and western regions of the island.

PMID- 20685292
TI  - Vitek 2 ANC card versus BBL Crystal Anaerobe and RapID ANA II for identification
      of clinical anaerobic bacteria.
AB  - The Vitek 2 Anaerobe and Corynebacterium Identification Card (ANC) was recently
      evaluated in a multicentre study. In the present work, this system was compared
      with the BBL Crystal Anaerobe and RapID ANA II panels. These kits were tested
      using 196 strains of anaerobes that had been previously identified by gas-liquid
      chromatography. Identification to the species or to the genus level was 75.0%,
      81.1% and 70.9% for Crystal, RapID and Vitek, respectively. Vitek ANC failed to
      provide any identification in 20.4% of the strains, but it had fewer
      misidentifications than RapID. The confidence factors provided on the results
      report of each kit were not always correlated with a lower risk of major errors,
      with the exception of Vitek 2 in which a confidence factor higher than 0.86
      excluded the risk of misidentification in more than 87% of isolates. The lower
      rate of identification by the Vitek and Crystal panels is mostly due the lower
      ability of these systems to identify the Clostridia. Overall, the three panels
      are comparable but need improvement to a better accuracy.

PMID- 20685293
TI  - Mother counts: how effects of environmental contaminants on maternal care could
      affect the offspring and future generations.
AB  - Various compounds of anthropogenic origin represent environmental contaminants
      (EC) that penetrate the food chain and are frequently detected in human milk and
      maternal blood at the time of delivery. These ECs can affect the development of
      the fetus and can be transferred to the newborn during lactation. Many studies
      have used animal models to study the impact of ECs on the development of the
      nervous system and have reported effects of early exposure on neural and
      neuroendocrine systems and on behavior, when the exposed animals are tested as
      adults. Some of these effects persist across generations and may involve
      epigenetic mechanisms. The majority of these studies in developmental toxicology
      treat the pregnant or lactating animal with ECs in order to deliver the
      contaminants to the developing offspring. Almost universally, the mother is
      viewed as a passive conduit for the ECs, and maternal behavior is rarely
      assessed. Here we review the literature on the effects of ECs on maternal care
      and find mounting evidence that important components of the care given to the
      offspring are affected by maternal exposure to different ECs. Some of these
      changes in maternal behavior appear to be secondary to changes in the behavior
      and/or stimulus properties of the exposed offspring, but others are likely to be
      direct effects of the ECs on the maternal nervous and endocrine systems.
      Considering the extent to which the quality of maternal care affects the
      development of the offspring, it becomes imperative to determine the
      contributions that changes in maternal behavior make to the deficits
      traditionally ascribed solely to direct effects of ECs on the developing
      organism. Given the complexity and importance of mother-infant interactions,
      future research on developmental toxicology must consider the effects of ECs not
      only on the offspring, but also on the mother and on the interactions and social
      bond between mother and infant.

PMID- 20685295
TI  - Mechanically strong geopolymers offer new possibilities in treatment of chronic
      pain.
AB  - We propose that a clay derived class of materials, known as geopolymers, may
      solve the problem of finding materials for controlled release with the right
      combination of properties necessary for a safe and sustained oral delivery of
      highly potent opioids. We show that the opioid Fentanyl, and its structurally
      similar sedative Zolpidem, can be embedded into metakaolin based geopolymer
      pellets to provide prolonged release dosage forms with mechanical strengths of
      the same order of magnitude as that of human teeth. The results presented in the
      current work may open up new opportunities for future development of drug
      delivery for high potency drugs employing high-strength and variable-pore
      structure geopolymers and materials alike.

PMID- 20685294
TI  - Brugia filariasis differentially modulates persistent Helicobacter pylori
      gastritis in the gerbil model.
AB  - In select Helicobacter pylori-infected populations with low gastric cancer,
      nematode coinfections are common and both helicobacter gastritis and filariasis
      are modeled in gerbils. We evaluated gastritis, worm counts, tissue cytokine gene
      expression levels and Th1/Th2-associated antibody responses in H. pylori and
      Brugia pahangi mono- and coinfected gerbils. H. pylori-associated gastritis
      indices were significantly lower 21 weeks post-infection in coinfected gerbils (p
      < or = 0.05) and were inversely proportional to worm counts (r(2) = -0.62, p <
      0.003). Additionally, IFN-gamma, IL-1 beta, CXCL1, IL-4 and IL-10 mRNA levels in
      the gastric antrum reflected a significant host response to gastric H. pylori and
      as well as systemic filariasis (p < or = 0.05). Despite increasing worm burden (p
      < 0.05), gastritis progressed in coinfected gerbils (p < 0.03) becoming
      equivalent to H. pylori-infected gerbils at 42 weeks (p = 0.7). Pro- and anti
      inflammatory mediator mRNA levels were notably downregulated in B. pahangi
      infected gerbils below uninfected control values, suggesting hyporesponsiveness
      to B. pahangi. Consistent with an increasing Th1 response to H. pylori, IgG2a (p
      < 0.01), IL-1 beta (p = 0.04) and CXCL1 (p = 0.006) responses significantly
      increased and IL-4 (p = 0.05) and IL-10 (p = 0.04) were decreased in coinfected
      gerbils at 42 weeks. Initial systemic responses to B. pahangi resulted in
      attenuated gastritis in coinfected gerbils, but subsequent filarid-associated
      hyporesponsiveness appears to have promoted H. pylori gastritis.

PMID- 20685296
TI  - Introduction. The 9th International Symposium on Chromosomal Aberrations.

PMID- 20685298
TI  - Cellular and soluble markers of tumor angiogenesis: from patient selection to the
      identification of the most appropriate postresistance therapy.
AB  - Antiangiogenic drugs are now intensively used in clinical oncology, but some
      drawbacks still hamper their development. First, it is frequently unclear what
      patient subpopulation is likely to gain clinical benefit from these expensive
      therapies; second, there is evidence of (sometimes rapid) development of drug
      resistance in many patients; third, the results of some preclinical and clinical
      studies have suggested acceleration of malignant cell aggressiveness when some
      antiangiogenic therapies are terminated. Here we discuss the role of soluble
      molecules and cellular markers of neoplastic angiogenesis for patient selection
      and follow-up during treatment. These markers should help clinicians to decide
      the right therapy, advise them of the generation of mechanisms of drug resistance
      during antiangiogenic treatment, and finally suggest the most appropriate next
      line of therapy according to the new patterns of cancer vascularization induced
      by antiangiogenic therapies.

PMID- 20685299
TI  - Molecular identification of unsaturated uronate reductase prerequisite for
      alginate metabolism in Sphingomonas sp. A1.
AB  - In Sphingomonas sp. A1, alginate is degraded by alginate lyases to its
      constituent monosaccharides, which are nonenzymatically converted to an alpha
      keto acid, namely, 4-deoxy-l-erythro-5-hexoseulose uronic acid (DEH). The
      properties of the DEH-metabolizing enzyme and its gene in strain A1 were
      characterized. In the presence of alginate, strain A1 cells inducibly produced an
      NADPH-dependent DEH reductase (A1-R) in their cytoplasm. Molecular cloning of the
      enzyme gene indicated that A1-R belonged to the short-chain
      dehydrogenase/reductase superfamily and catalyzed the conversion of DEH to 2-keto
      3-deoxy-d-gluconic acid most efficiently at around pH 7.0 and 50 degrees C.
      Crystal structures of A1-R and its complex with NADP were determined at around
      1.6A resolution by X-ray crystallography. The enzyme consists of three layers
      (alpha/beta/alpha), with a coenzyme-binding Rossmann fold. NADP is surrounded by
      positively charged residues, and Gly-38 and Arg-39 are crucial for NADP binding.
      Site-directed mutagenesis studies suggest that Ser-150, Tyr-164, and Lys-168
      located around the Rossmann fold constitute the catalytic triad. To our
      knowledge, this is the first report on molecular cloning and structure
      determination of a bacterial DEH reductase responsible for alginate metabolism.

PMID- 20685300
TI  - Unique biochemical properties of the protein tyrosine phosphatase activity of
      PTEN-demonstration of different active site structural requirements for
      phosphopeptide and phospholipid phosphatase activities of PTEN.
AB  - Missense PTEN mutations of the active site residues Asp-92, Cys-124 and Gly-129
      contribute to Cowden syndrome. How their mutations affect phospholipid
      phosphatase activity and tumor suppressor function of PTEN has been defined. In
      this study, we investigated how their mutations affect the kinetics and catalytic
      mechanism of PTEN phosphoprotein phosphatase activity. Our data suggest that PTEN
      catalysis of phosphoprotein dephosphorylation follows a two-step mechanism with
      Cys-124 transiently phosphorylated to form the phosphoenzyme intermediate. In
      spite of this, we were unable to trap the genuine phosphoenzyme intermediate;
      instead, we unexpectedly discovered a novel phosphotransfer reaction in which the
      phosphate group is transferred from a tyrosyl phosphopeptide to PTEN to form a
      unique phosphorylated protein. Even though the finding is novel, the
      phosphotransfer reaction is likely an in vitro non-enzymatic reaction. Kinetic
      analysis revealed that mutation of Asp-92 has negligible impacts on
      phosphopeptide phosphatase activity of PTEN, suggesting that Asp-92 does not
      participate in the phosphopeptide dephosphorylation reaction. The results also
      imply that allosteric regulators facilitating the recruitment of Asp-92 to
      participate in catalysis will increase the activity of PTEN in dephosphorylating
      phosphoprotein and phosphopeptide substrates. Furthermore, kinetic analysis
      revealed that the G129E mutation has different effects on phospholipid and
      phosphoprotein phosphatase activities. Taken together, the data show that while
      the two phosphatase activities of PTEN follow a similar catalytic mechanism, they
      have notable differences in the requirements of the active site structure.

PMID- 20685303
TI  - Hypotensive action of naturally occurring diterpenes: a therapeutic promise for
      the treatment of hypertension.
AB  - Plants have always been an exemplary source of drugs and many of the currently
      available medicines have been directly or indirectly derived from them. For this
      reason, the research, development and use of natural products as therapeutic
      agents, especially those derived from plants, have been increasing in recent
      years. A great deal of attention has focused on the naturally occurring
      antispasmodic phytochemicals as potential drugs for the treatment of
      cardiovascular diseases. Arterial hypertension is a common and progressive
      disorder that poses a major risk for cardiovascular and renal diseases. Recent
      data have revealed that the global burden of hypertension is an important and
      increasing public health problem worldwide and that the level of awareness,
      treatment and control of hypertension varies considerably among countries. The
      research on naturally occurring blood pressure-lowering agents is rapidly
      expanding due to the high potential of such molecules as new antihypertensive
      drugs. Recently, a great number of plant-derived substances, such as
      diterpenoids, have been evaluated as possible antihypertensive agents. Naturally
      occurring diterpenes such as forskolin and stevioside, exhibit vasorelaxant
      action and inhibit vascular contractility by different mechanisms of action. In
      this review we will discuss the mechanisms underlying the hypotensive action
      displayed by diterpenes and their potential use in human hypertension. We will
      also discuss the use of these compounds in the treatment of glaucoma, which is
      characterized by increased intraocular pressure (IOP).

PMID- 20685306
TI  - Needs for and environmental risks from transgenic crops in the developing world.
AB  - The developing world has many unique constraints to crop production and, lacking
      inputs, they are best overcome if solutions are seed borne. Classical breeding
      cannot overcome many of these constraints because the species have attained a
      'genetic glass ceiling', the genes are not available within the species.
      Transgenics can supply the genes, but typically not as 'hand me down genes' from
      the developed world because of the unique problems: mainly parasitic weeds, and
      weedy rice, stem borers and post-harvest insects, viral diseases, tropical
      mycotoxins, anti-feedants, toxic heavy metals and mineral deficiencies. Public
      sector involvement is imperative for genetically engineering against these
      constraints, as the private biotechnology sector does not see the developing
      world as a viable market in most instances. Rice, sorghum, barley, wheat and
      millets have related weeds, and in certain cases, transgenic gene containment
      and/or mitigation is necessary to prevent establishment of transgenes in the
      weedy relatives.

PMID- 20685307
TI  - Behavioral assessment of cognitive function using a translational neonatal piglet
      model.
AB  - Pigs are used in myriad research disciplines related to human health, but no
      studies have employed the piglet to directly assess cognitive function during the
      neonatal period. Our objective was to develop a behavioral assay for neonatal
      piglets to assess learning and memory. At 2-wk of age, piglets were trained to
      locate a milk reward in an 8-arm radial maze using colored intra-maze cues
      (acquisition phase, 60-s trials with 8 trials per d for 4d). Cue colors were then
      reversed and pigs re-tested to assess learning and working memory (reversal
      phase). Piglets quickly learned the simple associative acquisition task, and
      proficiency greatly improved throughout reversal testing. To further assess the
      behavioral assay, piglets received an i.p. injection of saline or
      polyinosinic:polycytidylic acid (poly I:C; 5mg/kg body weight) immediately
      preceding reversal testing. Poly I:C-treated piglets exhibited acute sickness
      behaviors, but observationally, were asymptomatic 12-h post-injection. Pro
      inflammatory cytokine mRNA expression was elevated 4-h post-injection in both
      peripheral and central compartments, and plasma cytokine protein levels were
      concurrently elevated. Specifically, poly I:C elicited the largest increases in
      interleukin (IL)-1beta mRNA in the liver, spleen, and hippocampus. At 24-, 48-,
      and 72-h post-injection (i.e., after acute sickness), poly I:C-treated piglets
      committed more incorrect arm entries, required more time to complete the reversal
      task, and moved a greater distance in the maze compared with control piglets.
      Collectively, these data demonstrate that neonatal piglets are capable of being
      trained in traditional learning and memory tests, and peripheral immune
      activation elicits alterations in cognitive processing in the neonate.

PMID- 20685308
TI  - Screening optimized protein purification protocols by coupling small-scale
      expression and mini-size exclusion chromatography.
AB  - Testing several different growth and purification conditions by means of a small
      scale screening is a valuable approach for identifying optimal protocols for
      large preparative protein productions. The availability of new mini columns for
      size exclusion chromatography (SEC) enables the coupling of parallel affinity
      purification using magnetic beads with the aggregation analysis performed by gel
      filtration. Only 35 MUL of bead eluate are sufficient to run both experiments and
      each SEC cycle needs no more than 30 min, washing and equilibration inclusive. We
      have shown that SEC ideally completes the SDS-PAGE analysis since it allows
      estimating the amount of soluble aggregates recovered in the elution fraction
      after affinity purification, although larger aggregates seem to be lost in the
      pre-column filters. SEC is also useful to identify low molecular mass
      contaminants that can be underestimated as they migrate together with the front
      of the acrylamide gel.

PMID- 20685309
TI  - The RETHINK project on minipigs in the toxicity testing of new medicines and
      chemicals: conclusions and recommendations.
AB  - The objective of the RETHINK project was to evaluate the potential impact of
      toxicity testing in the minipig as an alternative approach in regulatory toxicity
      testing that can contribute to the replacement, refinement and reduction of
      animal testing (3Rs). Expert study groups (Working Groups) were assembled to
      review five different areas relating to the use of minipigs in regulatory safety
      testing: ethical issues, welfare and animal care, development of new medicines
      and chemicals, safety testing issues and emerging technologies in safety testing.
      The conclusions and recommendations of the projects are presented in this
      article. It is concluded that there are no specific areas where restrictions to
      the use of minipigs in toxicology are required for welfare reasons. The minipig
      model is generally acceptable to regulatory authorities, provided it is
      adequately justified. The minipig is an interesting model for safety testing
      since there are numerous anatomical, physiological, genetic and biochemical
      similarities to humans. In addition many features of the minipig make it a
      practical and flexible model for safety testing. The use of the minipig in
      development of products does not bring any financial penalty in terms of the cost
      of testing. Benefits in terms of 3Rs can be identified in terms of life-cycle
      analysis of the use of minipigs compared to dogs and non-human primates. Finally
      the minipig (unlike the dog) is well positioned to take advantage of genomics and
      gene manipulation technologies. Specific recommendations for further research are
      made, which could bring 3Rs benefits. To deploy the minipig to the best
      advantage, clear information is needed about the predictivity of the minipig for
      human toxicities, and focussed action to define the potential role of the minipig
      in testing of biologics.

PMID- 20685310
TI  - The utility of the minipig as an animal model in regulatory toxicology.
AB  - In this article we review the value and utility of the minipig as an animal model
      in regulatory toxicity testing. Our review is based on detailed consideration of
      the comparative biology of the minipig, and of the practical features of toxicity
      testing in the minipig. The minipig presents a favourable profile as a non-rodent
      toxicology model, in terms of the similarity to man and also in terms of
      applicability to different study types. Studies of general toxicology can be
      performed in the minipig by oral, cutaneous, parenteral and inhalation routes.
      For reproductive toxicology studies the minipig offers numerous advantages as a
      non-rodent model although the lack of placental transfer of macromolecules may
      limit the role of the minipig in reproductive testing of biotechnology products.
      For safety pharmacology studies the minipig is an advantageous model,
      particularly as regards the cardiovascular system. The immune system of the pig
      is better characterized than that of the dog, making the pig an interesting
      alternative model to the nonhuman primate for therapeutic approaches based on
      manipulation of the immune system. Overall, this review leads us to believe that
      the minipig might be a better non-rodent toxicology model than the dog. At the
      present time, however, insufficient comparative data is available to permit a
      rigorous evaluation of the predictivity of the minipig for human drug-induced
      toxicities and research is urgently needed to provide experimental data for
      evaluation of the hypothesis that minipig studies may better reflect human drug
      induced toxicities than studies performed in traditional non-rodent toxicology
      models. It would be of particular value to gain a better vision of the potential
      utility of the minipig as a model for the safety testing of new biologics, where
      the minipig could potentially replace the use of non-human primates in the
      testing of some new products.

PMID- 20685311
TI  - The minipig as a platform for new technologies in toxicology.
AB  - The potential of the minipig as a platform for future developments in genomics,
      high density biology, transgenic technology, in vitro toxicology and related
      emerging technologies was reviewed. Commercial interests in the pig as an
      agricultural production species have driven scientific progress in these areas.
      There is no equivalent economic driver for progress in the dog or the monkey. As
      a result the available knowledge-bases are much greater for pigs (than for dogs
      or monkeys) in many areas (physiology, disease, genetics, immunology etc).
      Fundamental genomic knowledge and phenotypic characterization in regard to the
      pig is well in advance of the dog or the monkey and basic knowledge of the pig is
      therefore likely to stay ahead of the other two species. While the emerging
      technologies are essentially "species neutral" and can in principle be applied to
      all species, for all the technologies that we examined, basic knowledge and
      technical capabilities are greater for the pig than the dog or monkey. In
      concrete terms, in application to safety testing we have seen that: (i) The
      Gottingen minipig is well positioned for the performance of toxicogenomics
      studies, (ii) The close sequence homology between pigs and humans suggest that
      minipigs will be useful for the testing of biotechnology products (and possibly
      for in silico toxicology) and (iii) the minipig is the only non-rodent toxicology
      model where transgenic animals can be readily generated, and reproductive
      technologies are well developed in the pig. These properties should also make the
      minipig an interesting model for the testing of biotechnology products. These
      factors all support the idea that the minipig is well placed to meet the
      challenges of the emerging technologies and the toxicology of the future; it also
      seems likely that the minipig can be an advantageous model for the testing of
      biotechnology products.

PMID- 20685313
TI  - Widespread cortical expression of MANF by AAV serotype 7: localization and
      protection against ischemic brain injury.
AB  - Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a secreted protein
      which reduces endoplasmic reticulum (ER) stress and has neurotrophic effects on
      dopaminergic neurons. Intracortical delivery of recombinant MANF protein protects
      tissue from ischemic brain injury in vivo. In this study, we examined the
      protective effect of adeno-associated virus serotype 7 encoding MANF in a rodent
      model of stroke. An AAV vector containing human MANF cDNA (AAV-MANF) was
      constructed and verified for expression of MANF protein. AAV-MANF or an AAV
      control vector was administered into three sites in the cerebral cortex of adult
      rats. One week after the vector injections, the right middle cerebral artery
      (MCA) was ligated for 60min. Behavioral monitoring was conducted using body
      asymmetry analysis, neurological testing, and locomotor activity. Standard
      immunohistochemical and western blotting procedures were conducted to study MANF
      expression. Our data showed that AAV-induced MANF expression is redistributed in
      neurons and glia in cerebral cortex after ischemia. Pretreatment with AAV-MANF
      reduced the volume of cerebral infarction and facilitated behavioral recovery in
      stroke rats. In conclusion, our data suggest that intracortical delivery of AAV
      MANF increases MANF protein production and reduces ischemic brain injury.
      Ischemia also caused redistribution of AAV-mediated MANF protein suggesting an
      injury-induced release.

PMID- 20685314
TI  - Monoclonal anti-claudin 1 antibodies prevent hepatitis C virus infection of
      primary human hepatocytes.
AB  - BACKGROUND & AIMS: Hepatitis C virus (HCV) infection is a challenge to prevent
      and treat because of the rapid development of drug resistance and escape. Viral
      entry is required for initiation, spread, and maintenance of infection, making it
      an attractive target for antiviral strategies. The tight junction protein claudin
      1 (CLDN1) has been shown to be required for entry of HCV into the cell. METHODS:
      Using genetic immunization, we produced 6 monoclonal antibodies against the host
      entry factor CLDN1. The effects of antibodies on HCV infection were analyzed in
      human cell lines and primary human hepatocytes. RESULTS: Competition and binding
      studies demonstrated that antibodies interacted with conformational epitopes of
      the first extracellular loop of CLDN1; binding of these antibodies required the
      motif W(30)-GLW(51)-C(54)-C(64) and residues in the N-terminal third of CLDN1.
      The monoclonal antibodies against CLDN1 efficiently inhibited infection by HCV of
      all major genotypes as well as highly variable HCV quasispecies isolated from
      individual patients. Furthermore, antibodies efficiently blocked cell entry of
      highly infectious escape variants of HCV that were resistant to neutralizing
      antibodies. CONCLUSIONS: Monoclonal antibodies against the HCV entry factor CLDN1
      might be used to prevent HCV infection, such as after liver transplantation, and
      might also restrain virus spread in chronically infected patients.

PMID- 20685315
TI  - Toward automated workflow analysis and visualization in clinical environments.
AB  - Lapses in patient safety have been linked to unexpected perturbations in clinical
      workflow. The effectiveness of workflow analysis becomes critical to
      understanding the impact of these perturbations on patient outcome. The typical
      methods used for workflow analysis, such as ethnographic observations and
      interviewing, are limited in their ability to capture activities from different
      perspectives simultaneously. This limitation, coupled with the complexity and
      dynamic nature of clinical environments makes understanding the nuances of
      clinical workflow difficult. The methods proposed in this research aim to provide
      a quantitative means of capturing and analyzing workflow. The approach taken
      utilizes recordings of motion and location of clinical teams that are gathered
      using radio identification tags and observations. This data is used to model
      activities in critical care environments. The detected activities can then be
      replayed in 3D virtual reality environments for further analysis and training.
      Using this approach, the proposed system augments existing methods of workflow
      analysis, allowing for capture of workflow in complex and dynamic environments.
      The system was tested with a set of 15 simulated clinical activities that when
      combined represent workflow in trauma units. A mean recognition rate of 87.5% was
      obtained in automatically recognizing the activities.

PMID- 20685316
TI  - A virtual reality simulator for orthopedic basic skills: a design and validation
      study.
AB  - Orthopedic drilling as a skill demands high levels of dexterity and expertise
      from the surgeon. It is a basic skill that is required in many orthopedic
      procedures. Inefficient drilling can be a source of avoidable medical errors that
      may lead to adverse events. It is hence important to train and evaluate residents
      in safe environments for this skill. This paper presents a virtual orthopedic
      drilling simulator that was designed to provide visiohaptic interaction with
      virtual bones. The simulation provides a realistic basic training environment for
      orthopedic surgeons. It contains modules to track and analyze movements of
      surgeons, in order to determine their surgical proficiency. The simulator was
      tested with senior surgeons, residents and medical students for validation
      purposes. Through the multi-tiered testing strategy it was shown that the
      simulator was able to produce a learning effect that transfers to real-world
      drilling. Further, objective measures of surgical performance were found to be
      able to differentiate between experts and novices.

PMID- 20685318
TI  - A mathematical model of intercellular signaling during epithelial wound healing.
AB  - Recent experiments monitoring the healing process of wounded epithelial
      monolayers have demonstrated the necessity of MAPK activation for coordinated
      cell movement after damage. This MAPK activity is characterized by two wave-like
      phenomena. One MAPK "wave" that originates immediately after injury, propagates
      deep into the cell sheet, away from the edge, and then rebounds back to the wound
      interface. After this initial MAPK activity has largely disappeared, a second
      MAPK front propagates slowly from the wound interface and also continues into the
      cell sheet, maintaining a sustained level of MAPK activity throughout the cell
      sheet. It has been suggested that the first wave is initiated by Reactive Oxygen
      Species (ROS) generated at the time of injury. In this work, we develop a minimal
      mathematical model that reproduces the observed behavior. The main ingredients of
      our model are a competition between ligand (e.g., Epithelial Growth Factor) and
      ROS for the activation of Epithelial Growth Factor Receptor, and a feedback loop
      between receptor occupancy and MAPK activation. We explore the mathematical
      properties of the model and look for traveling wave solutions consistent with the
      experimentally observed MAPK activity patterns.

PMID- 20685321
TI  - Mitochondrial dysfunction in CD4+ lymphocytes from stavudine-treated HIV
      patients.
AB  - HIV therapy with nucleoside analogue reverse transcriptase inhibitors (NRTI) such
      as stavudine remains in widespread use in resource-limited nations due to potent
      efficacy, convenience of formulation and lack of practical alternatives. However,
      it remains unclear whether adverse side effects with NRTI include reduced
      mitochondrial respiratory function, particularly in peripheral blood lymphocytes
      (PBLs). The aim of this study was to determine whether stavudine-based highly
      active antiretroviral therapy (HAART) is associated with impaired mitochondrial
      respiratory transport chain function in patient derived CD4+PBLs. CD4+PBLs were
      isolated from asymptomatic HIV-infected patients treated with stavudine-HAART for
      3 months (n=10), HIV-infected patients not on treatment (n=9) and uninfected
      controls (n=18). The basal mitochondrial oxygen consumption of CD4+PBLs from
      stavudine-treated patients was reduced relative to that of untreated HIV-infected
      patients and controls (stavudine treated group, 4.22 (25% 2.16, 75% 8.84);
      control uninfected, 11.2 (25% 3.95, 75% 16.6); untreated 18.1 (25% 11.8, 75%
      37.9)ng oxygen atoms/min/ml). Maximal oxygen consumption (stimulated with the
      proton ionophore FCCP) in cells from stavudine treated patients was also reduced
      relative to that of untreated patients and controls (stavudine treated, 24.4+/
      10.5; control uninfected, 50.6+/-39.5; untreated, 68.8+/-41.1 ng oxygen
      atoms/min/ml). Citrate synthase activities, relative mitochondrial volume (by
      electron microscopy) and mtDNA copy numbers per cell were not different between
      groups. Therapy with stavudine results in impaired mitochondrial function in
      CD4+PBLs that does not appear to be due to reduced mitochondrial volume or DNA
      content and cannot be attributed to infection with HIV.

PMID- 20685322
TI  - Lung cancer proteomics, clinical and technological considerations.
AB  - The overall survival of lung cancer patients is disappointingly low. This is due
      to several factors, including the lack of an effective screening strategy to
      detect tumors at a potentially curable early stage, a marked resistance of lung
      cancer cells to drug treatment and a still superficial knowledge about the
      multifactorial cellular networks that are activated or suppressed during cancer
      progression. Furthermore, the armamentarium of clinicians and researchers in the
      field does not yet include reliable biomarkers to predict tumor response to
      treatment and foresee the natural history of the disease. In the present
      situation, a potential breakthrough is presented by proteomics technologies with
      the potential to discover relevant biomarkers which can be accurately quantified
      in multiplexed assays. Proteomics field can also contribute greatly in the
      understanding of mechanisms in tumor progression and treatment response. In this
      review we will describe the work that is being done in the field of lung cancer
      proteomics, focusing on clinically relevant questions that need to be addressed
      and on the possible applications of novel technologies.

PMID- 20685323
TI  - Computational biomechanics of the distal tibia from high-resolution MR and micro
      CT images.
AB  - The mechanical properties of bone estimated by micro-finite element (microFE)
      analysis on the basis of in vivo micro-MR images (microMRIs) of the distal
      extremities provide a new tool for direct assessment of the mechanical
      consequences of intervention. However, the accuracy of the method has not
      previously been investigated. Here, we compared microFE-derived mechanical
      parameters obtained from microMRIs at 160 microm isotropic voxel size now
      achievable in vivo with those derived from 25 microm isotropic (reference)
      microCT images of 30 cadaveric tibiae from 15 donors (4 females and 11 males,
      aged 55-84 years). Elastic and shear moduli estimated from 5mm(3) subvolumes of
      trabecular bone (TB) derived from microMRIs were significantly correlated with
      those derived from volume-matched reference microCT images (R(2)=0.60-0.67).
      Axial stiffness of whole-bone sections (including both cortical and trabecular
      compartments) derived from microMR-based models were highly correlated
      (R(2)=0.85) with those from high-resolution reference images. Further, microFE
      models generated from microCT images after downsampling to lower resolutions
      relevant to in vivo microMRI (100-160 microm) showed mechanical parameters to be
      strongly correlated (R(2)>0.93) with those derived at reference resolution (25
      microm). Incorporation of grayscale image information into the microMR-based
      microFE model yielded slopes closer to unity than binarized models (1.07+/-0.15
      vs. 0.71+/-0.11) when correlated with reference subregional elastic and shear
      moduli. This work suggests that elastic properties of distal tibia can be
      reliably estimated by microFE analysis from microMRIs obtainable at in vivo
      resolution.

PMID- 20685326
TI  - The Riesz transform and simultaneous representations of phase, energy and
      orientation in spatial vision.
AB  - To represent the local orientation and energy of a 1-D image signal, many models
      of early visual processing employ bandpass quadrature filters, formed by
      combining the original signal with its Hilbert transform. However,
      representations capable of estimating an image signal's 2-D phase have been
      largely ignored. Here, we consider 2-D phase representations using a method based
      upon the Riesz transform. For spatial images there exist two Riesz transformed
      signals and one original signal from which orientation, phase and energy may be
      represented as a vector in 3-D signal space. We show that these image properties
      may be represented by a Singular Value Decomposition (SVD) of the higher-order
      derivatives of the original and the Riesz transformed signals. We further show
      that the expected responses of even and odd symmetric filters from the Riesz
      transform may be represented by a single signal autocorrelation function, which
      is beneficial in simplifying Bayesian computations for spatial orientation.
      Importantly, the Riesz transform allows one to weight linearly across orientation
      using both symmetric and asymmetric filters to account for some perceptual phase
      distortions observed in image signals - notably one's perception of edge
      structure within plaid patterns whose component gratings are either equal or
      unequal in contrast. Finally, exploiting the benefits that arise from the Riesz
      definition of local energy as a scalar quantity, we demonstrate the utility of
      Riesz signal representations in estimating the spatial orientation of second
      order image signals. We conclude that the Riesz transform may be employed as a
      general tool for 2-D visual pattern recognition by its virtue of representing
      phase, orientation and energy as orthogonal signal quantities.

PMID- 20685325
TI  - Synthesis and functional analysis of novel bivalent estrogens.
AB  - The steroid hormone estrogen plays a critical role in female development and
      homeostasis. Estrogen mediates its effects through binding and activation of
      specific estrogen receptors alpha (ERalpha) and beta (ERbeta), members of the
      steroid/nuclear receptor family of ligand-induced transcription factors. Due to
      their intimate roles in genomic and nongenomic signaling pathways, these hormones
      and their receptors have been also implicated in the pathologies of a variety of
      cancers and metabolic disorders, and have been the target of large therapeutic
      development efforts. The binding of estrogen to its respective receptors
      initiates a cascade of events that include receptor dimerization, nuclear
      localization, DNA binding and recruitment of co-regulatory protein complexes. In
      this manuscript, we investigate the potential for manipulating steroid receptor
      gene expression activity through the development of bivalent steroid hormones
      that are predicted to facilitate hormone receptor dimerization events. Data are
      presented for the development and testing of novel estrogen dimers, linked
      through their C-17 moiety, that can activate estrogen receptor alpha (ERalpha)
      mediated transcription events with efficacy and potency equal to or greater than
      that of ERalpha's cognate ligand, 17beta-estradiol. These bivalent estrogen
      structures open the door to the development of a variety of steroid therapeutics
      that could dramatically impact future drug development in this area.

PMID- 20685327
TI  - Natural Killer Cells During Primary Varicella Zoster Virus Infection.

PMID- 20685328
TI  - Molecular mechanisms of antithrombin-heparin regulation of blood clotting
      proteinases. A paradigm for understanding proteinase regulation by serpin family
      protein proteinase inhibitors.
AB  - Serpin family protein proteinase inhibitors regulate the activity of serine and
      cysteine proteinases by a novel conformational trapping mechanism that may itself
      be regulated by cofactors to provide a finely-tuned time and location-dependent
      control of proteinase activity. The serpin, antithrombin, together with its
      cofactors, heparin and heparan sulfate, perform a critical anticoagulant function
      by preventing the activation of blood clotting proteinases except when needed at
      the site of a vascular injury. Here, we review the detailed molecular
      understanding of this regulatory mechanism that has emerged from numerous X-ray
      crystal structures of antithrombin and its complexes with heparin and target
      proteinases together with mutagenesis and functional studies of heparin
      antithrombin-proteinase interactions in solution. Like other serpins,
      antithrombin achieves specificity for its target blood clotting proteinases by
      presenting recognition determinants in an exposed reactive center loop as well as
      in exosites outside the loop. Antithrombin reactivity is repressed in the absence
      of its activator because of unfavorable interactions that diminish the favorable
      RCL and exosite interactions with proteinases. Binding of a specific heparin or
      heparan sulfate pentasaccharide to antithrombin induces allosteric activating
      changes that mitigate the unfavorable interactions and promote template bridging
      of the serpin and proteinase. Antithrombin has thus evolved a sophisticated means
      of regulating the activity of blood clotting proteinases in a time and location
      dependent manner that exploits the multiple conformational states of the serpin
      and their differential stabilization by glycosaminoglycan cofactors.

PMID- 20685331
TI  - Interaction and self-organization of human mesenchymal stem cells and neuro
      blastoma SH-SY5Y cells under co-culture conditions: A novel system for modeling
      cancer cell micro-environment.
AB  - The common drawback of many in vitro cell culture systems is the absence of
      appropriate micro-environment, which is formed by the combination of factors such
      as cell-cell contacts, extracellular matrix and paracrine regulation. Micro
      environmental factors in a tumor tissue can influence physiological status of the
      cancer cells and their susceptibility to anticancer therapies. Interaction of
      cancer cells with their micro-environment and regional stem cells, therefore, is
      of particular interest. Development of in vitro systems which allow more accurate
      modeling of complex relations occurring in real tumor environments can increase
      efficiency of preclinical assays for screening anticancer drugs. The aim of this
      work was to study interactions between human mesenchymal stem cells (MSCs) and
      neuro-blastoma cancer SH-SY5Y cells under co-culture conditions on different
      coated surfaces to determine the effect of co-existence of cancer and stem cells
      on each cellular population under various stress conditions. We developed an
      efficient in vitro system for studying individual cancer and stem cell
      populations during co-culture using differential live fluorescent membrane
      labeling, and demonstrated self-organization of cancer and stem cells during co
      culture on various coated surfaces. Our findings support the evidence that cancer
      and stem cell interactions play important roles in cellular behavior of cancer
      cells. These properties can be used in different fields of cancer research,
      tissue engineering and biotechnology.

PMID- 20685332
TI  - Semifluorinated alkanes--a new class of excipients suitable for pulmonary drug
      delivery.
AB  - INTRODUCTION: Semifluorinated alkanes (SFAs) are considered as diblock molecules
      with fluorocarbon and hydrocarbon segments. Unlike Perfluorocarbons (PFCs), SFAs
      have the potential to dissolve several lipophilic or water-insoluble substances.
      This makes them possibly suitable as new excipients for inhalative liquid drug
      carrier systems. PURPOSE: The aim of the study was to compare physico-chemical
      properties of different SFAs and then to test their respective effects in healthy
      rabbit lungs after nebulisation. METHODS: Physico-chemical properties of four
      different SFAs, i.e. Perfluorobutylpentane (F4H5), Perfluorohexylhexane (F6H6),
      Perfluorohexyloctane (F6H8) and Perfluorohexyldodecane (F6H12) were measured.
      Based on these results, aerosol characteristics of two potential candidates
      suitable as excipients for pulmonary drug delivery, i.e. F6H8 and F4H5, were
      determined by laser light diffraction. Tracheotomised and ventilated New Zealand
      White rabbits were nebulised with either a high- or a low dose of SFAs
      (F6H8(low/high) and F4H5(low/high)) or saline (NaCl). Ventilated healthy animals
      served as controls (Sham). Arterial blood gases, lung mechanics, heart rate and
      blood pressure were recorded prior to nebulisation and in 30 min intervals during
      the 6-h study period. RESULTS: Out of the four SFAs studied initially, no
      satisfactory behaviour as a solvent has to be expected because of low
      lipophilicity for F6H6. Output rate during aerosolisation was very low for F6H12.
      F6H8 and F4H5 presented comparable aerosolisation characteristics and
      lipophilicity and were therefore tested in the in vivo model. Aerosol therapy,
      either SFAs or saline, impaired paO2/FiO2 ratio, dynamic lung compliance and
      respiratory mechanics in all groups, except for F4H5(low) group which behaved
      like the control group (Sham). F4H5(low) had no adverse effects on gas exchange
      or pulmonary mechanics. CONCLUSIONS: Perfluorobutylpentane (F4H5) in a low-dose
      application may be suitable as a new inhalable excipient in SFA-based pulmonary
      drug delivery systems for lipophilic or water-insoluble substances.

PMID- 20685333
TI  - Inclusion of telmisartan in mesocellular foam nanoparticles: drug loading and
      release property.
AB  - Spherical mesocellular foam (MCF) with a continuous 3-D pore system was
      synthesized using Pluronic 123 triblock polymer (P123) as a surfactant coupled
      with cetyltrimethyl ammonium bromide (CTAB) as a co-surfactant. The feasibility
      of the prepared MCF nanoparticles for oral drug delivery was studied. A model
      drug, telmisartan (TEL), was loaded onto MCF via a procedure involving a
      combination of adsorption equilibrium and solvent evaporation. The drug-release
      rate and the drug loading efficiency of spherical MCF were compared with those of
      fibrous SBA-15. Investigations using nitrogen adsorption, scanning electron
      microscopy (SEM), transmission electron microscopy (TEM), wide-angle X-ray
      scattering (WXRS), differential scanning calorimetry (DSC) and HPLC demonstrated
      the successful incorporation of TEL into the MCF host. It is found that spherical
      MCF has a high drug loading efficiency up to 42.9% (drug weight/total weight) and
      higher than that of SBA-15 with a pore diameter of 6.5 nm. It is shown that a
      fast release rate of TEL was obtained from MCF compared with SBA-15 and pure
      crystalline TEL using enzyme-free simulated gastric fluid (pH 1.2) and intestinal
      fluid (pH 6.8). We believe that the present study will help in the design of oral
      drug delivery systems for the dissolution enhancement of water-insoluble drugs.

PMID- 20685334
TI  - Molecular characterization and RNA interference of three midgut aminopeptidase N
      isozymes from Bacillus thuringiensis-susceptible and -resistant strains of
      sugarcane borer, Diatraea saccharalis.
AB  - Aminopeptidase N (APN) proteins located at the midgut epithelium of some
      lepidopteran species have been implicated as receptors for insecticidal proteins
      from Bacillus thuringiensis. cDNAs of three APN isoforms, DsAPN1, DsAPN2, and
      DsAPN3, from Cry1Ab-susceptible (Cry1Ab-SS) and -resistant (Cry1Ab-RR) strains of
      the sugarcane borer, Diatraea saccharalis (F.) (Lepidoptera: Crambidae), were
      identified and sequenced using reverse transcriptase polymerase chain reaction
      (RT-PCR) and 5' rapid amplification of cDNA end (5' RACE). The characteristic APN
      sequence features were derived from deduced amino acid sequences of the cloned
      cDNAs. cDNA sequences of the three APN genes were identical between the Cry1Ab-SS
      and -RR strains. However, total APN proteolytic activity and gene expression of
      the three APNs from Cry1Ab-RR larvae were significantly lower than those of the
      Cry1Ab-SS strain. RNA interference (RNAi) was employed using an oral droplet
      feeding technique for the three APNs of the Cry1Ab-SS strain. Down-regulating
      expressions of the three APN genes by RNAi were corresponding to the reductions
      in the specific APN activity. In addition, silencing of all three APNs in D.
      saccharalis in vivo by RNAi resulted in a decrease in Cry1Ab susceptibility. Our
      results showed that reduction in expression of the three APNs is functionally
      associated with the Cry1Ab resistance in D. saccharalis.

PMID- 20685335
TI  - The orthologue to the Cpm1/Cqm1 receptor in Aedes aegypti is expressed as a
      midgut GPI-anchored alpha-glucosidase, which does not bind to the insecticidal
      binary toxin.
AB  - Aedes aegypti larvae are refractory to the insecticidal binary (Bin) toxin from
      Bacillus sphaericus, which is not able to bind to its target tissue in the larval
      midgut. In contrast, Culex pipiens larvae are highly susceptible to that toxin,
      which targets its midgut brush border membranes (BBMF) through the binding of the
      BinB subunit to specific receptors, the Cpm1/Cqm1 membrane-bound alpha
      glucosidases. The identification of an Ae. aegypti gene encoding a Cpm1/Cqm1
      orthologue, here named Aam1, led to the major goal of this study which was to
      investigate its expression. The aam1 transcript was found in larvae and adults
      from Ae. aegypti and a ~73-kDa protein was recognized by an anti-Cqm1 antibody in
      midgut BBMF. The Aam1 protein displayed alpha-glucosidase activity and localized
      to the midgut epithelium, bound through a GPI anchor, similarly to Cpm1/Cqm1.
      However, no binding of native Aam1 was observed to the recombinant BinB subunit.
      Treatment of both proteins with endoglycosidase led to changes in the molecular
      weight of Aam1, but not Cqm1, implying that the former was glycosylated. The
      findings from this work rule out lack of receptors in larval stages, or its
      expression as soluble proteins, as a reason for Ae. aegypti refractoriness to Bin
      toxin.

PMID- 20685336
TI  - Biochemical properties of heterologously expressed and native adenylyl cyclases
      from the honeybee brain (Apis mellifera L.).
AB  - Cyclic AMP is an important intracellular signaling molecule participating e.g. in
      sensory signal transduction, cardiac myocyte regulation, learning and memory. The
      formation of cAMP is catalyzed by adenylyl cyclases. A variety of factors can
      modulate the properties of these enzymes and lead to dynamic changes of the
      intracellular cAMP concentration. Here we determined the tissue distribution of a
      recently cloned adenylyl cyclase (AmAC3) in honeybee brain. The protein is
      present in all neuropils. Intensive immunoreactivity was found in parts of the
      proto- and deutocerebrum and in the suboesophageal ganglion. Biochemical and
      pharmacological properties of AmAC3 and of native adenylyl cyclases in subregions
      of the honeybee brain were examined. Values for half-maximal activation with
      NKH477 were in the low micromolar range with 10.2 MUM for AmAC3 and 3.6-8.1 MUM
      for native enzymes. Biosynthesis of cAMP was specifically blocked by P-site
      inhibitors. Adenylyl cyclases in antennal lobes and AmAC3 share the inhibitory
      profile with 2',5'dd3'ATP>3'AMP>2'deoxyadenosine. In addition to P-site
      inhibitors AmAC3 activity was impaired by Ca(2+)/calmodulin. The results suggest
      that AmAC3 is a likely candidate to fulfill an integrative role in sensory, motor
      and higher-order information processing in the honeybee brain.

PMID- 20685337
TI  - Palmitoylation and function of glial glutamate transporter-1 is reduced in the
      YAC128 mouse model of Huntington disease.
AB  - Excitotoxicity plays a key role in the selective vulnerability of striatal
      neurons in Huntington disease (HD). Decreased glutamate uptake by glial cells
      could account for the excess glutamate at the synapse in patients as well as
      animal models of HD. The major molecule responsible for clearing glutamate at the
      synapses is glial glutamate transporter GLT-1. In this study, we show that GLT-1
      is palmitoylated at cysteine38 (C38) and further, that this palmitoylation is
      drastically reduced in HD models both in vitro and in vivo. Palmitoylation is
      required for normal GLT-1 function. Blocking palmitoylation either with the
      general palmitoylation inhibitor, 2-bromopalmitate, or with a GLT-1 C38S
      mutation, severely impairs glutamate uptake activity. In addition, GLT-1-mediated
      glutamate uptake is indeed impaired in the YAC128 HD mouse brain, with the defect
      in the striatum evident as early as 3 months prior to obvious neuropathological
      findings, and in both striatum and cortex at 12 months. These phenotypes are not
      a result of changes in GLT1 protein expression, suggesting a crucial role of
      palmitoylation in GLT-1 function. Thus, it appears that impaired GLT-1
      palmitoylation is present early in the pathogenesis of HD, and may influence
      decreased glutamate uptake, excitotoxicity, and ultimately, neuronal cell death
      in HD.

PMID- 20685338
TI  - Cholinergic transmission in the dorsal hippocampus modulates trace but not delay
      fear conditioning.
AB  - Although cholinergic mechanisms have been widely implicated in learning and
      memory processes, few studies have investigated the specific contribution of
      hippocampal cholinergic transmission during trace fear conditioning, a form of
      associative learning involving a temporal gap between two stimuli. Microinfusions
      of scopolamine, a muscarinic receptor antagonist, into the dorsal hippocampus
      (DH) produced dose-dependent impairment in the acquisition and expression of a
      conditioned response (CR) following trace fear conditioning with a tone
      conditioned stimulus (CS) and a footshock unconditioned stimulus (US) in rats.
      The same infusions, however, had no effect on delay conditioning, general
      activity, pain sensitivity or attentional modulation. Moreover, scopolamine
      infusions attenuated phosphorylation of extracellular signal-regulated kinase
      (ERK) in the amygdala, indicating that cholinergic signals in the DH are
      important for trace fear conditioning. Taken together, the current study provides
      evidence that cholinergic neurotransmission in the DH is essential for the
      cellular processing of CS-US association in the amygdala when the two stimuli are
      temporally disconnected.

PMID- 20685339
TI  - Outer membrane vesicles function as offensive weapons in host-parasite
      interactions.
AB  - Outer membrane vesicles (OMVs), ubiquitously shed from Gram-negative bacteria,
      contain various virulence factors such as toxins, proteases, adhesins, and
      lipopolysaccharide, which are utilized to establish a colonization niche,
      modulate host defense and response, and impair host cell function. Thus, OMVs can
      be considered as a type of bacterial offensive weapon. This review discusses the
      entry mechanism of OMVs into host cells as well as their etiological roles in
      host-parasite interactions.

PMID- 20685340
TI  - Increased risk of respiratory tract infections in children with Down syndrome:
      the consequence of an altered immune system.
AB  - Down syndrome (DS) is the most common chromosomal abnormality among live-born
      infants. Respiratory tract infections are the most important cause of mortality
      in individuals with DS at all ages. In recent decades several studies have been
      performed to elucidate abnormalities of the immune system in DS. However, the
      influence of the immune system on the occurrence of respiratory tract infections
      in these children has never been reviewed.

PMID- 20685341
TI  - The pattern recognition receptors Nod1 and Nod2 account for neutrophil
      recruitment to the lungs of mice infected with Legionella pneumophila.
AB  - The intracellular bacterium Legionella pneumophila induces a severe form of
      pneumonia called Legionnaires diseases, which is characterized by a strong
      neutrophil (NE) infiltrate to the lungs of infected individuals. Although the
      participation of pattern recognition receptors, such as Toll-like receptors, was
      recently demonstrated, there is no information on the role of nod-like receptors
      (NLRs) for bacterial recognition in vivo and for NE recruitment to the lungs.
      Here, we employed a murine model of Legionnaires disease to evaluate host and
      bacterial factors involved in NE recruitment to the mice lungs. We found that L.
      pneumophila type four secretion system, known as Dot/Icm, was required for NE
      recruitment as dot/icm mutants fail to trigger NE recruitment in a process
      independent of bacterial multiplication. By using mice deficient for Nod1, Nod2,
      and Rip2, we found that these receptors accounted for NE recruitment to the lungs
      of infected mice. In addition, Rip2-dependent responses were important for
      cytokine production and bacterial clearance. Collectively, these studies show
      that Nod1, Nod2, and Rip2 account for generation of innate immune responses in
      vivo, which are important for NE recruitment and bacterial clearance in a murine
      model of Legionnaires diseases.

PMID- 20685342
TI  - Interference with islet-specific homing of autoreactive T cells: an emerging
      therapeutic strategy for type 1 diabetes.
AB  - Pathogenesis of type 1 diabetes involves the activation of autoimmune T cells,
      consequent homing of activated lymphocytes to the pancreatic islets and ensuing
      destruction of insulin-producing b cells. Interaction between activated
      lymphocytes and endothelial cells in the islets is the hallmark of the homing
      process. Initial adhesion, firm adhesion and diapedesis of lymphocytes are the
      three crucial steps involved in the homing process. Cell-surface receptors
      including integrins, selectins and hyaluronate receptor CD44 mediate the initial
      steps of homing. Diapedesis relies on a series of proteolytic events mediated by
      matrix metalloproteinases. Here, molecular mechanisms governing transendothelial
      migration of the diabetogenic effector cells are discussed and resulting
      pharmacological strategies are considered.

PMID- 20685343
TI  - Virtual drug discovery with the rise of Chinese CROs.

PMID- 20685344
TI  - Development of search filters for retrieval of literature on the molecular
      epidemiology of cancer.
AB  - OBJECTIVE: The available tools for searching literature in the area of molecular
      epidemiology of cancer, a relatively novel discipline, are largely
      unsatisfactory. The aim of this project was to develop two search filters in
      MEDLINE that would facilitate the retrieval of studies on cancer molecular
      epidemiology and to compare their performance. METHODS: Citations of all articles
      published in 2007 in three top journals in this area were hand-screened to
      establish a gold standard reference set of relevant papers. Two filters were
      created with this set: the first was based on the frequency of descriptors listed
      in the National Library of Medicine (NLM) Medical Subject Headings Thesaurus
      (MeSH terms) only, the second was based on the frequency of words in titles and
      abstracts (text-words), besides MeSH terms. The sensitivity, specificity,
      precision and accuracy rates of the two filters were calculated as performance
      measures. RESULTS: Out of all 1602 published articles, 344 were found to be
      pertinent to cancer molecular epidemiology; these formed the gold standard set.
      The first filter was the most specific (99%) and showed a good precision (93.2%),
      the second showed a higher sensitivity (78.2%) and accuracy (91.6%). CONCLUSION:
      The two filters proposed here represent a balance between sensitivity and
      specificity. Redefinition and elaboration of more appropriate NLM MeSH terms
      could greatly facilitate the retrieval of studies on the molecular epidemiology
      of cancer. Authors themselves could facilitate this by inserting adequate words
      in title or abstract of their articles.

PMID- 20685345
TI  - The function and evolution of Wnt genes in arthropods.
AB  - Wnt signalling is required for a wide range of developmental processes, from
      cleavage to patterning and cell migration. There are 13 subfamilies of Wnt ligand
      genes and this diverse repertoire appeared very early in metazoan evolution. In
      this review, we first summarise the known Wnt gene repertoire in various
      arthropods. Insects appear to have lost several Wnt subfamilies, either
      generally, such as Wnt3, or in lineage specific patterns, for example, the loss
      of Wnt7 in Anopheles. In Drosophila and Acyrthosiphon, only seven and six Wnt
      subfamilies are represented, respectively; however, the finding of nine Wnt genes
      in Tribolium suggests that arthropods had a larger repertoire ancestrally. We
      then discuss what is currently known about the expression and developmental
      function of Wnt ligands in Drosophila and other insects in comparison to other
      arthropods, such as the spiders Achaearanea and Cupiennius. We conclude that
      studies of Wnt genes have given us much insight into the developmental roles of
      some of these ligands. However, given the frequent loss of Wnt genes in insects
      and the derived development of Drosophila, further studies of these important
      genes are required in a broader range of arthropods to fully understand their
      developmental function and evolution.

PMID- 20685354
TI  - Development of new acetylcholinesterase reactivators: molecular modeling versus
      in vitro data.
AB  - In this work a theoretical methodology for evaluation of the association and
      kinetic reactivation constants of oximes using the Molegro and Spartan softwares
      was proposed and validated facing in vitro data previously reported in the
      literature. Results showed a very good agreement between the theoretical binding
      free energies of the reactivators and experimental data, suggesting that the
      proposed methodology could work well in the prediction of kinetic and
      thermodynamics parameters for oximes that might be helpful for the design and
      selection of new and more effective oximes.

PMID- 20685355
TI  - Biochemical mechanism of caffeic acid phenylethyl ester (CAPE) selective toxicity
      towards melanoma cell lines.
AB  - In the current work, we investigated the in vitro biochemical mechanism of
      Caffeic Acid Phenylethyl Ester (CAPE) toxicity and eight hydroxycinnamic/caffeic
      acid derivatives in vitro, using tyrosinase enzyme as a molecular target in human
      SK-MEL-28 melanoma cells. Enzymatic reaction models using tyrosinase/O(2) and
      HRP/H(2)O(2) were used to delineate the role of one- and two-electron oxidation.
      Ascorbic acid (AA), NADH and GSH depletion were used as markers of quinone
      formation and oxidative stress in CAPE induced toxicity in melanoma cells.
      Ethylenediamine, an o-quinone trap, prevented the formation of o-quinone and
      oxidations of AA and NADH mediated by tyrosinase bioactivation of CAPE. The
      IC(50) of CAPE towards SK-MEL-28 melanoma cells was 15muM. Dicoumarol, a
      diaphorase inhibitor, and 1-bromoheptane, a GSH depleting agent, increased CAPE's
      toxicity towards SK-MEL-28 cells indicating quinone formation played an important
      role in CAPE induced cell toxicity. Cyclosporin-A and trifluoperazine, inhibitors
      of the mitochondrial membrane permeability transition pore (PTP), prevented CAPE
      toxicity towards melanoma cells. We further investigated the role of tyrosinase
      in CAPE toxicity in the presence of a shRNA plasmid, targeting tyrosinase mRNA.
      Results from tyrosinase shRNA experiments showed that CAPE led to negligible anti
      proliferative effect, apoptotic cell death and ROS formation in shRNA plasmid
      treated cells. Furthermore, it was also found that CAPE selectively caused
      escalation in the ROS formation and intracellular GSH (ICG) depletion in
      melanocytic human SK-MEL-28 cells which express functional tyrosinase. In
      contrast, CAPE did not lead to ROS formation and ICG depletion in amelanotic C32
      melanoma cells, which do not express functional tyrosinase. These findings
      suggest that tyrosinase plays a major role in CAPE's selective toxicity towards
      melanocytic melanoma cell lines. Our findings suggest that the mechanisms of CAPE
      toxicity in SK-MEL-28 melanoma cells mediated by tyrosinase bioactivation of CAPE
      included quinone formation, ROS formation, intracellular GSH depletion and
      induced mitochondrial toxicity.

PMID- 20685356
TI  - Serotonin- and two putative serotonin receptors-like immunohistochemical
      reactivities in the ground crickets Dianemobius nigrofasciatus and Allonemobius
      allardi.
AB  - Serotonin (5-hydroxytryptamine; 5-HT)- and two putative serotonin receptors, 5
      HT1A- and 5-HT1B-like, immunohistochemical reactivities were investigated in the
      cephalic ganglia of two ground crickets, Dianemobius nigrofasciatus and
      Allonemobius allardi. 5-HT-ir was strongly expressed in the central body,
      accessory medulla region of the optic lobe, frontal ganglion, posterior cortex of
      the protocerebrum, dorsolateral region of the protocerebrum, and the
      suboesphageal ganglion (SOG) in both crickets. However, 5-HT1A-ir and 5-HT1B-ir
      showed quite mutually distinct patterns that were also distinct from 5-HT-ir. 5
      HT1A-ir was located in the pars intercerebralis, dorsolateral region of the
      protocerebrum, optic tract, optic lobe, and the midline of the SOG in both
      crickets. 5-HT1B-ir was located in the pars intercerebralis and dorsolateral
      region of the protocerebrum, and detected weakly in the optic lobe,
      tritocerebrum, and the midline of the SOG in both crickets. Interspecific
      differences were observed with 5-HT1A-ir. 5-HT1A-ir was expressed weakly in two
      neurons in the mandibular neuromere of the SOG in D. nigrofasciatus, while it was
      expressed strongly in the tritocerebrum, mandibular neuromere, and maxillary
      neuromere of the SOG in A. allardi and co-localized with CLOCK-ir (CLK-ir). 5HT
      1B-ir was co-localized with CLK-ir in the tritocerebrum, mandibular neuromere,
      and maxillary neuromere of the SOG when double-labeling was conducted in both
      crickets. These results indicated that 5-HT and both types of 5-HT receptors may
      regulate circadian photo-entrainment or photoperiodism in A. allardi, while only
      5-HT1B may be involved in circadian photo-entrainment or photoperiodism in D.
      nigrofasciatus.

PMID- 20685357
TI  - 4-hydroxy-2-nonenal protects against cardiac ischemia-reperfusion injury via the
      Nrf2-dependent pathway.
AB  - Reactive oxygen species (ROS) attack polyunsaturated fatty acids of the membrane
      and trigger lipid peroxidation, which results in the generation of alpha,beta
      unsaturated aldehydes, such as 4-hydroxy-2-nonenal (4-HNE). There is compelling
      evidence that high concentrations of aldehydes are responsible for much of the
      damage elicited by cardiac ischemia-reperfusion injury, while sublethal
      concentrations of aldehydes stimulate stress resistance pathways, to achieve
      cardioprotection. We investigated the mechanism of cardioprotection mediated by 4
      HNE. For cultured cardiomyocytes, 4-HNE was cytotoxic at higher concentrations
      (>or=20 microM) but had no appreciable cytotoxicity at lower concentrations.
      Notably, a sublethal concentration (5muM) of 4-HNE primed cardiomyocytes to
      become resistant to cytotoxic concentrations of 4-HNE. 4-HNE induced nuclear
      translocation of transcription factor NF-E2-related factor 2 (Nrf2), and enhanced
      the expression of gamma-glutamylcysteine ligase (GCL) and the core subunit of the
      Xc(-) high-affinity cystine transporter (xCT), thereby increasing 1.45-fold the
      intracellular GSH levels. Cardiomyocytes treated with either Nrf2-specific siRNA
      or the GCL inhibitor l-buthionine sulfoximine (BSO) were less tolerant to 4-HNE.
      Moreover, the cardioprotective effect of 4-HNE pretreatment against subsequent
      glucose-free anoxia followed by reoxygenation was completely abolished in these
      cells. Intravenous administration of 4-HNE (4 mg/kg) activated Nrf2 in the heart
      and increased the intramyocardial GSH content, and consequently improved the
      functional recovery of the left ventricle following ischemia-reperfusion in
      Langendorff-perfused hearts. This cardioprotective effect of 4-HNE was not
      observed for Nrf2-knockout mice. In summary, 4-HNE activates Nrf2-mediated gene
      expression and stimulates GSH biosynthesis, thereby conferring on cardiomyocytes
      protection against ischemia-reperfusion injury.

PMID- 20685358
TI  - Transmission dynamics of Toxoplasma gondii along an urban-rural gradient.
AB  - Recently, several authors have proposed that the availability of intermediate
      hosts (IHs) for definitive hosts (DHs) may contribute to determining the dynamics
      and evolutionary ecology of parasites with facultative complex life cycles. The
      protozoa Toxoplasma gondii may be transmitted to DHs either via predation of
      infected IHs through a complex life cycle (CLC) or directly from a contaminated
      environment through a simple life cycle (SLC). This parasite is also present in
      contrasting host density environments. We tested the hypothesis that the relative
      contributions of the CLC and SLC along an urban-rural gradient depend on the IH
      supply. We built and analysed a deterministic model of the T. gondii transmission
      cycle. The SLC relative contribution is important only in urban-type
      environments, i.e., with low predation rate on IHs. In contrast, the parasite is
      predominantly transmitted through a CLC in suburban and rural environments. The
      association of the two cycles enables the parasite to spread in situations of low
      IH availability and low DH population size for which each cycle alone is
      insufficient.

PMID- 20685359
TI  - Evaluation of radicals scavenging, immunity-modulatory and antitumor activities
      of longan polysaccharides with ultrasonic extraction on in S180 tumor mice
      models.
AB  - Longan (Dimocarpus longan Lour.) is used as a traditional edible and medicinal
      material in China. In this paper, the effects of polysaccharides from longan pulp
      with ultrasonic extraction (UELP) on the radicals scavenging, immunity-modulatory
      and antitumor activities in S180 tumor mice models were investigated. UELP showed
      excellent scavenging activity on the hydroxyl radicals and a,a-diphenyl-1
      picrylhydrazyl (DPPH) radicals, and obtained the almost complete scavenging
      effect. UELP with medium-dose (200mg/kg) and low-dose (100mg/kg) had potent
      immune-modulatory effects in S180 tumor mice model and exhibited significant
      effect on delayed-type hypersensitivity (DTH) response, macrophage phagocytosis
      and ConA-stimulated splenocyte proliferation as compared with model control
      treatment (p<0.01). The results still showed that UELP had great antitumor
      effects, and maximum inhibition rate was obtained at medium-dose and low-dose
      (200 and 100mg/kg).

PMID- 20685360
TI  - Microwave synthesis, characterization, and zinc uptake studies of starch-graft
      poly(ethylacrylate).
AB  - Microwave synthesis of starch-graft-poly(ethylacrylate) was optimized to obtain
      efficient Zn(II) adsorbent that has been characterized using IR, XRD and SEM
      analyses. Using the sample, adsorption of Zn(II) was studied as a function of pH,
      sorbent dose, initial Zn(II) concentration, % grafting, temperature and ionic
      strength. Equilibrium isotherm data were analyzed using the Langmuir and
      Freundlich isotherms at optimum pH (pH 8) where the data fitted satisfactorily
      well to both the isotherms indicating sorption of Zn(II) on the copolymer was
      complex and involved more than one mechanism. Isotherms have also been used to
      obtain the thermodynamic parameters such as free energy, enthalpy, and entropy of
      sorption. At 30 degrees C, the maximum sorption capacity of the microwave
      synthesized copolymer was 172mgg(-1) as compared to 116mgg(-1) for the
      conventionally synthesized starch-graft-poly(ethylacrylate) indicating the
      advantage of using microwaves in the copolymer synthesis. In order to investigate
      the mechanism of sorption,kinetic data were modeled using the first order
      Lagergren, pseudo-second-order and intra-particle diffusion models where
      chemisorption seem significant in the rate controlling step. The regeneration
      experiments revealed that the starch-graft-poly(ethylacrylate) can be
      successfully reused for five cycles without any significant loss in the sorption
      capacity.

PMID- 20685361
TI  - Immunosuppression promotes endogenous neural stem and progenitor cell migration
      and tissue regeneration after ischemic injury.
AB  - Recent work has demonstrated that self-repair in the adult brain can be augmented
      by the infusion of growth factors to activate endogenous neural precursor cells
      that contribute to new tissue formation and functional recovery in a model of
      stroke. Using both a genetic model and drug treatment, we demonstrate that
      immunosuppression mimics the effects of growth factor activation, including
      tissue regeneration, neural precursor cell migration and functional recovery
      following ischemic injury. In the absence of growth factor treatment, mice with a
      functional immune system develop a prominent cavity in the cortex underlying the
      ischemic injury. In untreated immunodeficient NOD/SCID mice, however, the
      cortical cavity forms but is then filled with regenerated cortical tissue
      containing glial cells and subependyma derived neural stem and progenitor cells
      that migrate from their niche lining the lateral ventricles. The daily
      administration of Cyclosporine A also results in endogenous neural precursor cell
      migration and regenerated cortical tissue at the site of the cortical injury.
      Different from growth factor-treated animals is the finding that the regenerated
      cortical tissue in immunosuppressed animals is devoid of new neurons.
      Interestingly, both the growth factor and immunosuppressed (NOD/SCID and
      Cyclosporine A) treated animals displayed functional behavioural recovery despite
      the lack of neurogenesis within the regenerated cortical tissue. This article is
      part of a Special Issue entitled "Interaction between repair, disease, &
      inflammation."

PMID- 20685362
TI  - A neurophysiological evaluation of a cognitive cycle in humans.
AB  - The present review describes and analyzes several recent papers in which the
      processes of preparation, evaluation and changing a cue's predictive value on a
      trial-by-trial basis conform a cycle that permits behavior to be constantly
      updated. This approach is an extension of Joaquin Fuster's proposal of a
      "perception-action" cycle in which executive networks are constantly updated as a
      function of the trials' outcome. The presented results can also be considered in
      relation to the computational Bayesian brain framework proposed by Friston
      (2009). The present approach is based on human electrophysiological studies of
      Posner's central cue paradigm, which provides the possibility to dissociate the
      following processing steps: (i) preparation for certain stimuli, (ii) evaluation
      of the validity or invalidity of the preparatory state, and (iii) the feedback
      cycling of the information extracted from one trial to the next. This trial-by
      trial learning would be a potential basis for organism adaptation.

PMID- 20685363
TI  - Neuroimaging for Lewy body disease: is the in vivo molecular imaging of alpha
      synuclein neuropathology required and feasible?
AB  - Alpha-synuclein aggregation is a neuropathological hallmark of many
      neurodegenerative diseases including Parkinson's disease (PD), Parkinson's
      disease with dementia (PDD) and dementia with Lewy bodies (DLB), collectively
      termed the alpha-synucleinopathies. Substantial advances in clinical criteria and
      neuroimaging technology over the last 20 years have allowed great strides in the
      detection and differential diagnosis of these disorders. Nevertheless, it is
      clear that whilst the array of different imaging modalities in clinical use allow
      for a robust diagnosis of alpha-synucleinopathy in comparison to healthy
      subjects, there is no clear diagnostic imaging marker that affords a reliable
      differential diagnosis between the different forms of Lewy body disease (LBD) or
      that could facilitate tracking of disease progression. This has led to a call for
      a biomarker based on the pathological hallmarks of these diseases, namely alpha
      synuclein-positive Lewy bodies (LBs). This potentially may be advantageous in
      terms of early disease detection, but may also be leveraged into a potential
      marker of disease progression. We here aim to firstly review the current status
      of neuroimaging biomarkers in PD and related synucleinopathies. Secondly, we
      outline the rationale behind alpha-synuclein imaging as a potential novel
      biomarker as well as the potential benefits and limitations of this approach.
      Thirdly, we attempt to illustrate the likely technical hurdles to be overcome to
      permit successful in vivo imaging of alpha-synuclein pathology in the diseased
      brain. Our overriding aim is to provide a framework for discussion of how to
      address this major unmet clinical need.

PMID- 20685365
TI  - Molecular characterization and gene expression of thyrotropin receptor (TSHR) and
      a truncated TSHR-like in Senegalese sole.
AB  - Thyroid hormones (THs) play a key role in larval development, growth and
      metamorphosis in flatfish. Their synthesis is tightly regulated by the
      hypothalamic-pituitary-thyroid axis. Thyroid-stimulating hormone receptor (TSHR)
      is a key protein in the control of thyroid function stimulating TH synthesis
      after binding its ligand, the thyrotropin. In teleost fish, numerous reports have
      associated the TSHR with gametogenesis. However, little information about its
      role during larval development is available. In this study, we report the cloning
      of two different cDNAs with high similarity to TSHR. Phylogenetic analysis
      clustered both cDNAs separately. One of them (referred to TSHR) grouped with TSHR
      orthologs in tetrapods and teleost fish and possessed the three typical conserved
      domains and regulatory motifs. The second receptor (referred to as TSHRtr-like)
      represented a novel truncated cDNA bearing the extracellular and part of the
      transmembrane domain. TSHRtr-like orthologs were only found in teleosts, which
      suggests that it could have appeared after fish-specific 3R genome duplication.
      Expression profiles of both genes are analyzed in juvenile tissues and during
      larval development using a real-time PCR approach. In juvenile fish, TSHR and
      TSHRtr-like are expressed ubiquitously although transcript levels varied between
      organs. In both cases, the highest mRNAs levels are detected in brain. During
      larval development, both genes are expressed to a high level during the first
      stages (2-3days after hatching) reducing progressively their abundance in the
      whole larvae during metamorphosis. This reduction in mRNA abundance is more
      accentuated for the TSHRtr-like gene. To evaluate the possible regulation of both
      receptors by T4 during sole metamorphosis, larvae are exposed to the goitrogen
      thiourea (TU). Only TSHRtr-like modifies its expression, increasing its
      transcripts at 11days after treatment. Moreover, adding exogenous T4 hormone to
      TU-treated larvae restores the TSHRtr-like steady-state levels similar to the
      untreated control. Overall, these results demonstrate the existence of two
      thyrotropin receptors differentially regulated by THs in teleosts.

PMID- 20685364
TI  - Reduced nicotinamide adenine dinucleotide phosphate oxidase 2 plays a key role in
      stellate cell activation and liver fibrogenesis in vivo.
AB  - BACKGROUND & AIMS: Hepatocyte apoptosis and activation of hepatic stellate cells
      (HSC) are critical events in fibrogenesis. We previously demonstrated that
      phagocytosis of apoptotic hepatocytes by HSC is profibrogenic. Based on this, as
      well as the observation that reduced nicotinamide adenine dinucleotide phosphate
      oxidase (NADPH) oxidase induction is central to fibrogenesis, our aim was to
      study the phagocytic NADPH oxidase NOX2. METHODS: An in vivo phagocytosis model
      was developed by injecting wild type (wt) or NOX2(-/-) mice with lentiviral-green
      fluorescence protein (GFP) containing a hepatocyte-specific promoter, and adeno
      tumor necrosis factor-related apoptosis-inducing ligand (ad-TRAIL). Fibrosis was
      evaluated in bile duct ligated (BDL) wt and NOX2(-/-) mice with or without
      gadolinium treatment. NOX2 expression was studied in human liver samples and in
      HSC isolated from fibrotic livers. The fibrogenic activity of NOX2 was assessed
      by collagen reporter assays. RESULTS: In the phagocytosis model, engulfment of
      GFP-labeled apoptotic bodies was seen, and the expression of alpha-smooth muscle
      actin (alpha-SMA) and collagen I increased significantly in the wt but not in the
      NOX2(-/-) mice. Inhibiting apoptosis decreased the profibrogenic response. NOX2(
      /-) animals exhibited significantly less fibrosis following BDL. Inactivating
      macrophages in wt BDL mice did not lower collagen production to the level
      observed in NOX2(-/-) mice, suggesting that NOX2-expressing HSC are important in
      fibrogenesis. NOX2 was up-regulated in HSC from fibrotic livers, and phagocytosis
      induced NOX2 expression and activity were demonstrated. Based on reporter assays,
      production of NOX2-mediated reactive oxygen species directly induced collagen
      promoter activity in HSC. CONCLUSIONS: Apoptosis and phagocytosis of hepatocytes
      directly induce HSC activation and initiation of fibrosis. NOX2, the phagocytic
      NADPH oxidase, plays a key role in this process and in liver fibrogenesis in
      vivo.

PMID- 20685366
TI  - Neural inputs of the hypothalamic "aggression area" in the rat.
AB  - A part of the mediobasal hypothalamus (known as hypothalamic attack area) plays a
      central role in the control of aggressive behavior as its electrical stimulation
      reliably and rapidly elicits biting attacks in cats and rodents. The efferent
      connections of this brain region were described in rats, but afferent pathways
      were not investigated so far. We injected the retrograde tracer cholera toxin B
      subunit into the mediobasal hypothalamus of male Wistar rats and studied the
      distribution of labeled cells by immunohistochemical method. The retrograde
      labeling outlined three continuous, distinct afferent cell populations: (i) a
      telencephalic midline "plate" containing the orbitofrontal - medial prefrontal -
      septal regions which ends in the bed nucleus of stria terminalis; (ii) a temporal
      column including the medial amygdala, amigdalohippocampal area and subiculum;
      (iii) a diffuse column along the medial hypothalamus which ends in the posterior
      hypothalamic nucleus. Sparse labeling was present in brainstem nuclei, except for
      the lateral parabrachial nucleus that provides a significant input. The
      projections of the medial prefrontal cortex to the hypothalamic attack area
      indicate a direct, earlier undescribed pathway with marked importance in the
      control of aggressive behavior. Similarly, we identified several brain regions
      which send very significant projections to the hypothalamic attack area but their
      importance in the control of aggressive behavior are nearly unknown. The
      comparison of the present and earlier findings shows that efferent and afferent
      connections overlap in many regions to a significant extent, suggesting that
      reverberating circuits are important in the control of aggressive behavior.

PMID- 20685367
TI  - Exploitation of a high genomic mutation rate in Solenopsis invicta virus 1 to
      infer demographic information about its host, Solenopsis invicta.
AB  - The RNA-dependent RNA polymerase (RdRp) region of Solenopsis invicta virus 1
      (SINV-1) was sequenced from 47 infected colonies of S. invicta, S. richteri, S.
      geminata, and S. invicta/richteri hybrids collected from across the USA, northern
      Argentina, and northern Taiwan in an attempt to infer demographic information
      about the recent S. invicta introduction into Taiwan by phylogenetic analysis.
      Nucleotide sequences were calculated to exhibit an overall identity of >90%
      between geographically-separated samples. A total of 171 nucleotide variable
      sites (representing 22.4% of the region amplified) were mapped across the SINV-1
      RdRp alignment and no insertions or deletions were detected. Phylogenetic
      analysis at the nucleotide level revealed clustering of Argentinean sequences,
      distinct from the USA sequences. Moreover, the SINV-1 RdRp sequences derived from
      recently introduced populations of S. invicta from northern Taiwan resided within
      the multiple USA groupings implicating the USA as the source for the recent
      introduction of S. invicta into Taiwan. Examination of the amino acid alignment
      for the RdRp revealed sequence identity >98% with only nine amino acid changes
      observed. Seven of these changes occurred in less than 4.3% of samples, while 2
      (at positions 1266 and 1285) were featured prominently. Changes at positions 1266
      and 1285 accounted for 36.2% and 34.0% of the samples, respectively. Two distinct
      groups were observed based on the amino acid residue at position 1266, Threonine
      or Serine. In cases where this amino acid was a Threonine, 90% of these sequences
      possessed a corresponding Valine at position 1285; only 10% of the
      Threonine(1266)-containing sequences possessed an Isoleucine at the 1285
      position. Among the Serine(1266) group, 76% possessed an Isoleucine at position
      1285, while only 24% possessed a Valine. Thus, it appears that the
      Threonine(1266)/Valine(1285) and Serine(1266)/Isoleucine(1285) combinations are
      predominant phenotypes.

PMID- 20685368
TI  - Toxinology in Brazil: A big challenge for a rich biodiversity.
AB  - Toxinology in Brazil developed specially during the 19th and 20th centuries. A
      very brief description of the main contributions made by pioneer toxinologists is
      presented here in an attempt to give an idea of the evolution of toxinology in
      our country, from its first steps until the XVI World Congress of the
      International Society on Toxinology, held in Recife, Brazil in March of 2009.

PMID- 20685370
TI  - Differential responses of the mammalian retinal ganglion cell line RGC-5 to
      physiological stimuli and trophic factors.
AB  - The rat retinal ganglion cell (RGC) line RGC-5 constitutes a widely used model
      for studying physiological processes in retinal cells. In this paper we
      investigated the expression of clock and immediately early genes, and calcium
      mediated responses to physiological stimuli in differentiated and mitotically
      active RGC-5 cells. To this end, we attempted to differentiate the RGC-5 cells
      with a variety of effectors classically used to induce morphological
      differentiation. No sign of morphological differentiation was observed after 24 h
      of treatment with BDNF (80 ng/mL), NGF (100 ng/mL) and retinoic acid (20 ng/mL),
      among others. Only staurosporine (SSP) was able to promote neurite outgrowth at
      concentrations ranging from 53.5 to 214 nM. However, apoptotic nuclei were seen
      at 24 h of treatment using DNA staining, and a few cells remained at 72 h post
      treatment. Concentrations of SSP lower than 214 nM were partially effective in
      inducing cell differentiation. Dividing RGC-5 cells express the RGC marker Thy-1
      and different clock genes such as Per1, Clock and Bmal1. When characterizing the
      responsiveness of proliferative RGC-5 cells we found that in most of them, brief
      pulses of 50% FBS induced c-Fos and PER1 expression. Subsets of RGC-5 cells
      displayed significant changes in intracellular Ca2+ levels by ATP (100 microM)
      but not by glutamate (100-200 microM) stimulation. On the basis of cell
      morphology, size and complexity and effector responsiveness it was possible to
      distinguish different subpopulations within the cell line. The results
      demonstrate that only SSP is effective in promoting RGC-5 morphological
      differentiation, though the treatment provoked cell death. Proliferative cells
      expressing the RGC marker Thy-1 and a number of clock genes, responded
      differentially to diverse physiological stimuli showing a rapid c-Fos and PER1
      induction by FBS stimulation, and an increase in intracellular Ca2+ by ATP.

PMID- 20685371
TI  - Evidence of conformational changes in adsorbed lysozyme molecule on silver
      colloids.
AB  - In this article, we discuss metal-protein interactions in the Ag-lysozyme complex
      by spectroscopic measurements. The analysis of the variation in relative
      intensities of SERS bands reveals the orientation and the change in conformation
      of the protein molecules on the Ag surface with time. The interaction kinetics of
      metal-protein complexes has been analyzed over a period of 3h via Raman
      measurements. Our analysis indicates that the Ag nanoparticles most likely
      interact with Trp123 which is in close proximity to Phe34 of the lysozyme
      molecule.

PMID- 20685372
TI  - Persistent dystonia following opioid withdrawal.

PMID- 20685373
TI  - Vagus-nerve stimulation is tolerated in a patient with cardiac AV-blocks.

PMID- 20685375
TI  - Dentin permeability reduction by a sequential application of calcium and fluoride
      phosphate solutions.
AB  - OBJECTIVE: A sequential topical application of calcium and fluoride-phosphate
      solutions was reported to occlude open dentin tubules, mainly with fluoroapatite
      precipitates by a rapid ionic reaction, and to be effective at treating dentin
      hypersensitivity. However, its ability to reduce dentin permeability (Lp) is
      unknown. The aim of this in vitro study was to evaluate the effect of this
      treatment on Lp. METHODS: Nine extracted human third molars were sectioned
      transversely to obtain 0.5 mm-thick discs, which were then etched and rinsed.
      Aqueous solutions of 5% (w/w) disodium phosphate containing 0.3% (w/w) sodium
      fluoride (A) and 10% (w/w) calcium chloride (B) were prepared. The sequential
      application of the A&B solutions was repeated three times on each disc, which was
      then rinsed with distilled water. The Lp of the discs was measured before and
      after the application using a modified Pashley's fluid flow measuring system. The
      differences in the Lp values between the conditions before and after the solution
      applications were analysed using a generalized estimating equation method and
      paired t-test. Scanning Electron Microscopy (SEM) was used to observe the dentin
      surfaces. RESULTS: All nine discs consistently indicated reduced Lp following the
      application of the A&B solutions. There was a significant decrease in the mean Lp
      [microL/(cm(2) s cm H(2)O)] from baseline (-0.27+/-0.25, p=0.011). Overall, an
      average decrease of 34% Lp occurred after the application of the A&B solutions.
      SEM observation indicated that the reaction products covered the entire dentin
      disc surface. CONCLUSION: The application of the A&B solutions was effective at
      reducing the Lp of the dentin discs.

PMID- 20685376
TI  - Experimental evidence of the reciprocal oxidation of Bovine Serum Albumin and
      Linoleate in aqueous solution, initiated by HO* free radicals.
AB  - An investigation of radiation-induced oxidation of aqueous bovine serum albumin
      (BSA) in the presence of linoleate (LH) at pH 10.5 has been carried out in order
      to better understand the respective oxidative processes involved in both lipid
      and protein phases. Solutions containing BSA (15 micromol L(-1)) and linoleate
      (15-600 micromol L(-1)) below the critical micellar concentration (cmc=2000
      micromol L(-1)), have been irradiated by gamma-rays (137Cs) at radiation doses
      ranging from 10 to 400 Gy (dose rate 9.5 Gy min(-1)). It can be noticed that, in
      the absence of BSA, the main hydroperoxides formed from HO*-induced linoleate
      oxidation below the cmc, do not exhibit a conjugated dienic structure. This was
      also verified in the presence of BSA. Selected chemical markers of oxidation have
      been monitored: non-conjugated dienic hydroperoxides and conjugated dienes
      (without hydroperoxide function) for linoleate oxidation, and carbonyl groups for
      BSA oxidation. We have shown that for the lowest linoleate concentration (15
      micromol L(-1)) in the presence of BSA (15 micromol L(-1)), the formation of
      conjugated dienes was not observed, meaning that LH was not exposed to HO*
      radicals attack. However, non-conjugated dienic lipid hydroperoxides were
      simultaneously detected, indicating that LH was secondarily oxidised by BSA
      oxidised species. Moreover, the oxidation of linoleate was found to be enhanced
      by the presence of BSA. For the highest linoleate concentration (600 micromol L(
      1)), the expected protection of BSA by LH was not observed, even if LH monomers
      were responsible for the total scavenging of HO* radicals. In this latter case,
      the formation of non-conjugated dienic lipid hydroperoxides was lower than
      expected. Those results showed that BSA was not oxidised by the direct action of
      HO* radicals but was undergoing a secondary oxidation by non-dienic lipid
      hydroperoxides and/or lipid radical intermediates, coming from the HO*-induced
      linoleate oxidation.

PMID- 20685378
TI  - A modeler's view on the spatial structure of intrinsic horizontal connectivity in
      the neocortex.
AB  - Most current computational models of neocortical networks assume a homogeneous
      and isotropic arrangement of local synaptic couplings between neurons. Sparse,
      recurrent connectivity is typically implemented with simple statistical wiring
      rules. For spatially extended networks, however, such random graph models are
      inadequate because they ignore the traits of neuron geometry, most notably
      various distance dependent features of horizontal connectivity. It is to be
      expected that such non-random structural attributes have a great impact, both on
      the spatio-temporal activity dynamics and on the biological function of
      neocortical networks. Here we review the neuroanatomical literature describing
      long-range horizontal connectivity in the neocortex over distances of up to eight
      millimeters, in various cortical areas and mammalian species. We extract the main
      common features from these data to allow for improved models of large-scale
      cortical networks. Such models include, next to short-range neighborhood
      coupling, also long-range patchy connections. We show that despite the large
      variability in published neuroanatomical data it is reasonable to design a
      generic model which generalizes over different cortical areas and mammalian
      species. Later on, we critically discuss this generalization, and we describe
      some examples of how to specify the model in order to adapt it to specific
      properties of particular cortical areas or species.

PMID- 20685381
TI  - Estimation methods for Maximum Residue Limits for pesticides.
AB  - Maximum Residue Limits (MRLs) are standards that represent the maximum residue
      concentration expected to be found if a pesticide is applied according to good
      agricultural practice (GAP). MRLs are established only where the residues in food
      resulting from particular use patterns of the pesticide pass the public health
      risk assessment. Foodstuffs are monitored for MRL compliance and MRL exceedance
      can have economic and trade consequences. There is a trade-off when deciding on
      values for MRLs. The aim is to establish MRLs at levels that are high enough to
      prevent chance exceedance but not so high that misuse will not be detected. Small
      data sets typically available for estimating MRLs present problems for
      establishing consistent values. A review of MRL estimation methods is presented
      together with an assessment of the various methods.

PMID- 20685377
TI  - Heat shock proteins: cellular and molecular mechanisms in the central nervous
      system.
AB  - Emerging evidence indicates that heat shock proteins (HSPs) are critical
      regulators in normal neural physiological function as well as in cell stress
      responses. The functions of HSPs represent an enormous and diverse range of
      cellular activities, far beyond the originally identified roles in protein
      folding and chaperoning. HSPs are now understood to be involved in processes such
      as synaptic transmission, autophagy, ER stress response, protein kinase and cell
      death signaling. In addition, manipulation of HSPs has robust effects on the fate
      of cells in neurological injury and disease states. The ongoing exploration of
      multiple HSP superfamilies has underscored the pluripotent nature of HSPs in the
      cellular context, and has demanded the recent revamping of the nomenclature
      referring to these families to reflect a re-organization based on structure and
      function. In keeping with this re-organization, we first discuss the HSP
      superfamilies in terms of protein structure, regulation, expression and
      distribution in the brain. We then explore major cellular functions of HSPs that
      are relevant to neural physiological states, and from there we discuss known and
      proposed HSP impacts on major neurological disease states. This review article
      presents a three-part discussion on the array of HSP families relevant to
      neuronal tissue, their cellular functions, and the exploration of therapeutic
      targets of these proteins in the context of neurological diseases.

PMID- 20685382
TI  - AR42J-B-13 cell: an expandable progenitor to generate an unlimited supply of
      functional hepatocytes.
AB  - Hepatocytes are the preparation of choice for Toxicological research in vitro.
      However, despite the fact that hepatocytes proliferate in vivo during liver
      regeneration, they are resistant to proliferation in vitro, do not tolerate sub
      culture and tend to enter a de-differentiation program that results in a loss of
      hepatic function. These limitations have resulted in the search for expandable
      rodent and human cells capable of being directed to differentiate into functional
      hepatocytes. Research with stem cells suggests that it may be possible to provide
      the research community with hepatocytes in vitro although to date, significant
      challenges remain, notably generating a sufficiently pure population of
      hepatocytes with a quantitative functionality comparable with hepatocytes. This
      paper reviews work with the AR42J-B-13 (B-13) cell line. The B-13 cell was cloned
      from the rodent AR42J pancreatic cell line, express genes associated with
      pancreatic acinar cells and readily proliferates in simple culture media. When
      exposed to glucocorticoid, 75-85% of the cells trans-differentiate into
      hepatocyte-like (B-13/H) cells functioning at a level quantitatively similar to
      freshly isolated rat hepatocytes (with the remaining cells retaining the B-13
      phenotype). Trans-differentiation of pancreatic acinar cells also appears to
      occur in vivo in rats treated with glucocorticoid; in mice with elevated
      circulating glucocorticoid and in humans treated for long periods with
      glucocorticoid. The B-13 response to glucocorticoid therefore appears to be
      related to a real pathophysiological response of a pancreatic cell to
      glucocorticoid. An understanding of how this process occurs and if it can be
      generated or engineered in human cells would result in a cell line with the
      ability to generate an unlimited supply of functional human hepatocytes in a cost
      effective manner.

PMID- 20685383
TI  - Preparation and evaluation of fexofenadine microemulsion for intranasal delivery.
AB  - To enhance the solubility and bioavailability of poorly absorbable fexofenadine,
      microemulsion system composed of oil, surfactant and co-surfactant was developed
      for intranasal delivery. Phase behavior, particle size, viscosity and
      solubilization capacity of the microemulsion system were characterized.
      Histopathology and in vivo nasal absorption of the optimized microemulsion
      formulations were also investigated in rats. A single isotropic region was found
      in the pseudo-ternary phase diagrams developed at various ratios with Lauroglycol
      90 as oil, Labrasol as surfactant and Plurol oleiqueCC49 or its mixture with PEG
      400 (1:1) as cosurfactant. An increase in the microemulsion region in pseudo
      ternary phase systems was observed with increased surfactant concentration. The
      optimized microemulsion formulations showed higher solubulization of
      fexofenadine, i.e., F1 (22.64mg/mL) and F2 (22.98mg/mL), compared to its
      intrinsic water solubility (1.51mg/mL). Nasal absorption of fexofenadine from
      these microemulsions was found to be fairly rapid. T(max) was observed within
      5min after intranasal administration at 1.0mg/kg dose, and the absolute
      bioavailability (0-4h) was about 68% compared to the intravenous administration
      in rats. Our results suggested that these microemulsion formulations could be
      used as an effective intranasal dosage form for the rapid-onset delivery of
      fexofenadine.

PMID- 20685379
TI  - The nicotinic acetylcholine receptor CHRNA5/A3/B4 gene cluster: dual role in
      nicotine addiction and lung cancer.
AB  - More than 1 billion people around the world smoke, with 10 million cigarettes
      sold every minute. Cigarettes contain thousands of harmful chemicals including
      the psychoactive compound, nicotine. Nicotine addiction is initiated by the
      binding of nicotine to nicotinic acetylcholine receptors, ligand-gated cation
      channels activated by the endogenous neurotransmitter, acetylcholine. These
      receptors serve as prototypes for all ligand-gated ion channels and have been
      extensively studied in an attempt to elucidate their role in nicotine addiction.
      Many of these studies have focused on heteromeric nicotinic acetylcholine
      receptors containing alpha4 and beta2 subunits and homomeric nicotinic
      acetylcholine receptors containing the alpha7 subunit, two of the most abundant
      subtypes expressed in the brain. Recently however, a series of linkage analyses,
      candidate-gene analyses and genome-wide association studies have brought
      attention to three other members of the nicotinic acetylcholine receptor family:
      the alpha5, alpha3 and beta4 subunits. The genes encoding these subunits lie in a
      genomic cluster that contains variants associated with increased risk for several
      diseases including nicotine dependence and lung cancer. The underlying mechanisms
      for these associations have not yet been elucidated but decades of research on
      the nicotinic receptor gene family as well as emerging data provide insight on
      how these receptors may function in pathological states. Here, we review this
      body of work, focusing on the clustered nicotinic acetylcholine receptor genes
      and evaluating their role in nicotine addiction and lung cancer.

PMID- 20685384
TI  - A physiological frequency-position map of the chinchilla cochlea.
AB  - Accumulating evidence indicates that mammalian cochlear frequency-position maps
      (location of maximum vibration of the basilar membrane as a function of
      frequency) depend on the physiological condition of the inner ear. Cochlear
      damage desensitizes the ear, after the damage the original location of maximum
      vibration is tuned to a lower sound frequency. This suggests that frequency
      position maps, derived from such desensitized ears, are shifted to lower
      frequencies, corresponding to a shift of the basilar membrane vibration pattern
      towards the base for a given stimulus frequency. To test this hypothesis, we re
      mapped the cochlear frequency-position map in the chinchilla. We collected
      frequency-position data from chinchillas in normal physiological condition
      ("physiological map") and compared these to data previously established from
      sound overexposed ears ("anatomical map"). The characteristic frequency (CF) of
      neurons in the cochlear nucleus was determined. Horse-radish peroxidase (HRP) or
      biocytin (BCT) were injected iontophoretically to trace auditory nerve fibers
      towards their innervation site in the organ of Corti. The relationship between
      distance from the base (d, percent) and frequency (f, kHz) was described best by
      a simple exponential function: d = 61.2 - 42.2 x log(f). The slope of the
      function was 2.55 mm/octave. Compared to the "anatomical map", the "physiological
      map" was shifted by about 0.3 octaves to higher frequencies corresponding to a
      shift of the basilar membrane vibration pattern of 0.8 mm towards the apex for a
      given stimulus frequency. Our findings affirm that frequency-position maps in the
      mammalian cochlea depend on the condition of the inner ear. Damage-induced
      desensitization in mammalian inner ears results in similar shifts of CF (about
      0.5 octaves) but different shifts of the maximum of the vibration pattern towards
      the base at given frequencies, dependent on the mapping constant of the species,
      longer basilar membranes showing a larger basal shift. Furthermore, the results
      substantiate the notion that "crowding" at lower frequencies appears to be a
      specialization rather than a general feature.

PMID- 20685387
TI  - Nuclear and plastid genetic engineering of plants: comparison of opportunities
      and challenges.
AB  - Plant genetic engineering is one of the key technologies for crop improvement as
      well as an emerging approach for producing recombinant proteins in plants. Both
      plant nuclear and plastid genomes can be genetically modified, yet fundamental
      functional differences between the eukaryotic genome of the plant cell nucleus
      and the prokaryotic-like genome of the plastid will have an impact on key
      characteristics of the resulting transgenic organism. So, which genome, nuclear
      or plastid, to transform for the desired transgenic phenotype? In this review we
      compare the advantages and drawbacks of engineering plant nuclear and plastid
      genomes to generate transgenic plants with the traits of interest, and evaluate
      the pros and cons of their use for different biotechnology and basic research
      applications, ranging from generation of commercial crops with valuable new
      phenotypes to 'bioreactor' plants for large-scale production of recombinant
      proteins to research model plants expressing various reporter proteins.

PMID- 20685388
TI  - A physiologically based model for temporal envelope encoding in human primary
      auditory cortex.
AB  - Communication sounds exhibit temporal envelope fluctuations in the low frequency
      range (<70 Hz) and human speech has prominent 2-16 Hz modulations with a maximum
      at 3-4 Hz. Here, we propose a new phenomenological model of the human auditory
      pathway (from cochlea to primary auditory cortex) to simulate responses to
      amplitude-modulated white noise. To validate the model, performance was estimated
      by quantifying temporal modulation transfer functions (TMTFs). Previous models
      considered either the lower stages of the auditory system (up to the inferior
      colliculus) or only the thalamocortical loop. The present model, divided in two
      stages, is based on anatomical and physiological findings and includes the entire
      auditory pathway. The first stage, from the outer ear to the colliculus,
      incorporates inhibitory interneurons in the cochlear nucleus to increase
      performance at high stimuli levels. The second stage takes into account the
      anatomical connections of the thalamocortical system and includes the fast and
      slow excitatory and inhibitory currents. After optimizing the parameters of the
      model to reproduce the diversity of TMTFs obtained from human subjects, a patient
      specific model was derived and the parameters were optimized to effectively
      reproduce both spontaneous activity and the oscillatory part of the evoked
      response.

PMID- 20685392
TI  - Fourteenth Workshop on Vitamin D.

PMID- 20685390
TI  - Defining the neurotoxin derived illness chronic ciguatera using markers of
      chronic systemic inflammatory disturbances: a case/control study.
AB  - BACKGROUND: Ciguatoxins are extremely potent neurotoxins, produced by tropical
      marine dinoflagellates, that persistently enter into our food web. Over 100,000
      people annually experience acute ciguatera poisoning from consuming toxic fish.
      Roughly 5% of these victims will develop chronic ciguatera (CC), a widespread,
      multisymptom, multisystem, chronic illness that can last tens of years. CC is
      marked by disproportionate disability and non-specific refractory symptoms such
      as fatigue, cognitive deficits and pain, and is suggestive of other illnesses.
      Its unknown pathophysiology makes both diagnosis and treatment difficult.
      OBJECTIVES: We wanted to compare objective parameters of visual contrast
      sensitivity testing, measures of innate immune response and genetic markers in
      cases to controls to assess the potential for the presence of persistent
      inflammatory parameters that are demonstrated in other biotoxin associated
      illnesses at a single specialty clinic. METHODS: Using 59 CC cases and 59
      controls we present in retrospective review, in all cases, abnormalities in
      immune responses paralleling the chronic systemic inflammatory response syndrome
      seen in several other chronic diseases. RESULTS: This study defines a preliminary
      case definition using medical history, total symptoms, visual contrast
      sensitivity, HLA DR genotype analysis, reduction of regulatory neuropeptides VIP
      and MSH, and multiple measures of inflammatory immune response, especially C4a
      and TGFbeta1, thereby providing a basis for identification and targeted therapy.
      CONCLUSIONS: CC provides a model for chronic human illness associated with
      initiation of inflammatory responses by biologically produced neurotoxins.

PMID- 20685393
TI  - Combining THz spectroscopy and MD simulations to study protein-hydration
      coupling.
AB  - THz spectroscopy is combined with MD simulations to study the dynamical
      properties of water in the solvation shell of proteins. The solvation dynamics is
      found to be influenced on length-scales of several hydration layers which is
      significantly more than what is found for static properties. Our experiments show
      that the properties of this dynamical solvation shell depend on the folding state
      of the protein. Kinetic THz absorption studies allow us to observe the formation
      of the dynamical solvation shell of the native protein upon folding. The
      experimental results can be reproduced using MD simulations which helps to
      develop a molecular understanding in terms of retardation of water dynamics.

PMID- 20685395
TI  - The RETHINK project--minipigs as models for the toxicity testing of new medicines
      and chemicals: an impact assessment.
AB  - The objective of the RETHINK project was to evaluate the potential impact of
      toxicity testing in the minipig as an alternative approach in regulatory toxicity
      testing that can contribute to the replacement, refinement and reduction of
      animal testing (3Rs). Minipigs are strains of domestic pigs that are markedly
      smaller than farmyard varieties, and thus better adapted to laboratory housing.
      The pig closely resembles man in many features of its anatomy, physiology,
      biochemistry and lifestyle. In particular, the cardio-vascular system, skin and
      digestive tract are considered to be very good models for man. Because of these
      similarities the toxic effects of chemicals and drugs in pigs may resemble the
      effects in man more closely than do some other commonly used laboratory animals.
      The pig also has some features that make it a very practical model for laboratory
      studies. Finally, being a food animal, testing in the minipig may be more
      acceptable to the public than animals such as dogs or monkeys. Expert study
      groups (Working Groups) were assembled to review five different areas relating to
      the use of minipigs in regulatory safety testing: ethical issues, welfare and
      animal care, development of new medicines and chemicals, safety testing issues
      and emerging technologies in safety testing. Their conclusions are presented in
      the articles of this special issue. The RETHINK project was funded as a Specific
      Support Action under the European Community 6th Framework Programme.

PMID- 20685396
TI  - Guinea pig neutrophil-macrophage interactions during infection with Mycobacterium
      tuberculosis.
AB  - We examined the ability of recombinant guinea pig IL-8 (CXCL8) to activate
      neutrophils upon infection with virulent Mycobacterium tuberculosis. Using a
      Transwell insert culture system, contact-independent cell cultures were studied
      in which rgpIL-8-treated neutrophils were infected with virulent M. tuberculosis
      in the upper well, and AM were cultured in the lower well. IL-1beta and TNF-alpha
      mRNA expression was significantly upregulated by AM. Neutralizing anti-rgpTNF
      alpha polyclonal antibody abrogated the response of AM to supernatants from the
      rgpIL-8-treated, infected neutrophils, while an anti-rgpIL-8 polyclonal antibody
      had no effect. This suggests that TNF-alpha produced by rgpIL-8 treated, infected
      neutrophils may play an important role in the activation of AM in the early
      response of the host against M. tuberculosis infection. Significant induction of
      apoptosis in M. tuberculosis-infected neutrophils was observed as compared to the
      uninfected neutrophils. Feeding of infected, apoptotic neutrophils to AM induced
      a significant up-regulation of TNF-alpha and IL-1beta mRNA compared to AM exposed
      to staurosporine-treated apoptotic neutrophils. Suppressed intracellular
      mycobacterial growth was also seen in AM fed with infected, apoptotic neutrophils
      as compared to the AM infected with M. tuberculosis H37Rv alone. Taken together,
      these data suggest that neutrophil-macrophage interactions may contribute to host
      defense against M. tuberculosis infection.

PMID- 20685398
TI  - Druggable pockets and binding site centric chemical space: a paradigm shift in
      drug discovery.
AB  - Detection, comparison and analyses of binding pockets are pivotal to structure
      based drug design endeavors, from hit identification, screening of exosites and
      de-orphanization of protein functions to the anticipation of specific and non
      specific binding to off- and anti-targets. Here, we analyze protein-ligand
      complexes and discuss methods that assist binding site identification, prediction
      of druggability and binding site comparison. The full potential of pockets is yet
      to be harnessed, and we envision that better understanding of the pocket space
      will have far-reaching implications in the field of drug discovery, such as the
      design of pocket-specific compound libraries and scoring functions.

PMID- 20685399
TI  - Increased cardiometabolic traits in pediatric survivors of acute lymphoblastic
      leukemia treated with total body irradiation.
AB  - Survivors of childhood acute lymphoblastic leukemia (ALL) may face an increased
      risk of metabolic and cardiovascular late effects. To determine the prevalence of
      and risk factors for adverse cardiometabolic traits in a contemporary cohort of
      pediatric ALL survivors, we recruited 48 off-therapy patients in remission
      treated with conventional chemotherapy and 26 treated with total body irradiation
      (TBI)-based hematopoietic cell transplantation (HCT) in this cross-sectional
      pilot study. At a median age of 15 years (range, 8-21 years), HCT survivors were
      significantly more likely than non-HCT survivors to manifest multiple
      cardiometabolic traits, including central adiposity, hypertension, insulin
      resistance, and dyslipidemia. Overall, 23.1% of HCT survivors met the criteria
      for metabolic syndrome (>= 3 traits), compared with 4.2% of non-HCT survivors (P
      = .02). HCT survivors also had increased C-reactive protein and leptin levels and
      decreased adiponectin, suggestive of underlying inflammation and increased
      visceral fat. In multivariate analyses, history of HCT remained associated with
      >= 2 traits (odds ratio [OR]. 5.13; 95% confidence interval [CI], 1.54-17.15) as
      well as with >= 3 traits (OR, 16.72; 95% CI, 1.66-168.80). Other risk factors
      included any cranial radiation exposure and family history of cardiometabolic
      disease. In summary, pediatric ALL survivors exposed to TBI-based HCT as well as
      to any cranial radiation may manifest cardiometabolic traits at an early age and
      should be screened accordingly.

PMID- 20685400
TI  - Factors associated with self-reported physical and mental health after
      hematopoietic cell transplantation.
AB  - Hematopoietic cell transplantation (HCT) is an intensive treatment for
      hematologic malignancies that has the potential to cure disease or prolong life,
      but also to impair quality of life for survivors. Earlier studies have suggested
      that various factors are associated with physical and mental health after HCT. In
      this study, we evaluated demographic and clinical factors before and after HCT
      and selected psychosocial factors after HCT, exploring their association with
      self-reported physical and mental health. We studied a cohort of 662 survivors at
      a median of 6.6 years after HCT. Pre-HCT demographic and clinical factors
      accounted for only a small amount of the variance in physical and mental health
      post-HCT (3% and 1%, respectively). Adding post-HCT clinical variables to the pre
      HCT factors accounted for 32% and 7% of physical and mental outcomes,
      respectively. When both clinical and psychosocial factors were considered, better
      physical health post-HCT was associated with younger age, race other than white,
      higher current family income, currently working or being a student, less severe
      transplantation experience (ie, not experiencing graft-versus-host disease),
      fewer current comorbidities, higher Karnofsky status, less social constraint,
      less social support, and less trait anxiety. This multivariate model accounted
      for 36% of the variance in physical health, with the psychosocial variables
      contributing very little. When both clinical and psychosocial factors were
      considered, better mental health after HCT was associated with more severe
      transplantation experience, less social constraint, greater spiritual well being,
      and less trait anxiety. This multivariate model accounted for 56% of the variance
      in mental health, with the psychosocial factors accounting for most of the
      variance. These data suggest that clinical factors are explanatory for much of
      the post-HCT physical health reported by HCT survivors, but very little of self
      perceived mental health. These observations provide insight into the
      identification of factors that can allow recognition of at-risk patients, as well
      as factors amenable to intervention.

PMID- 20685402
TI  - The flavonoids luteolin and quercetagetin inhibit lipoteichoic acid actions on
      H9c2 cardiomyocytes.
AB  - Dental focal infections are infections in the mouth that cause subsequent
      infection and symptoms in other parts of the body. Dental conditions such as
      periodontitis have been associated with coronary heart disease. In this study, we
      investigated the effect of flavonoids on activation of mitogen-activated protein
      kinase (MAPK) family members, protein kinase B (AKT), and IL-1 beta expression by
      rat heart embryonic (H9c2) cells upon stimulation with LTA. Pretreatment with
      four flavonoids, including quercetin, genistein, quercetagetin, and luteolin
      diminished LTA-induced ERK1/2, JNK, p38, and AKT phosphorylation and IL-1 beta
      gene expression. Our findings indicate that flavonoids interfere with LTA signal
      transduction.

PMID- 20685401
TI  - Atrial pacing or ventricular backup-only pacing in implantable cardioverter
      defibrillator patients.
AB  - BACKGROUND: The need for pacing support in typical ICD patients is unknown.
      OBJECTIVE: This study sought to determine whether atrial pacing with ventricular
      backup pacing is equivalent to ventricular backup pacing only in implantable
      cardioverter-defibrillator (ICD) patients. METHODS: We randomized 1,030 patients
      from 84 sites with indications for ICDs, with sinus rhythm, and without
      symptomatic bradycardia to atrial pacing with ventricular backup at 60 beats/min
      (518) or ventricular backup pacing at 40 beats/min (512). The primary end points
      were time to death, heart failure hospitalization (HFH), and heart failure
      related urgent care (HFUC). RESULTS: Follow-up was 2.4 +/- 0.8 years when the
      trial was stopped for futility. There were 355 end point events (103 deaths, 252
      HFH/HFUC) in 194 patients favoring ventricular backup pacing (event-free rate
      77.7% vs. 80.3% for atrial pacing at 30 months; hazard ratio 1.14, upper
      confidence bound 1.59, prespecified noninferiority threshold 1.21), therefore
      equivalence between pacing arms was not demonstrated. Overall HFH/HFUC rates were
      slightly higher during atrial pacing (event-free rate 85.4% vs. 86.4% for
      ventricular backup pacing). Exploratory analyses revealed that the difference in
      HFH/HFUC rates was largely seen in patients with a PR interval >=230 ms. There
      were no differences between groups for atrial fibrillation, ventricular
      tachycardia/ventricular fibrillation, quality of life, or echocardiographic
      measurements. Fewer patients in the atrial pacing group were reported to develop
      an indication for bradycardia pacing (3.7% vs. 7.3%, P = .0053). CONCLUSION:
      Equivalence between atrial pacing and ventricular backup pacing only could not be
      demonstrated. CLINICAL TRIALS IDENTIFIER: NCT00281099.

PMID- 20685403
TI  - Phosphoinositide 3-kinase gamma mediates chemotactic responses of human
      eosinophils to platelet-activating factor.
AB  - BACKGROUND: Eosinophils are characteristic participants in allergic inflammation.
      The intracellular signalling mechanisms involved in the migration of eosinophils
      to sites of allergic inflammation are poorly understood. Chemotactic responses of
      eosinophils to platelet-activating factor (PAF), but not eotaxin, have been
      demonstrated to be dependent upon the activation of phosphoinositide 3-kinase
      (PI3K) but the specific isoform of PI3K involved has not been identified.
      OBJECTIVE: To determine the roles of the leukocyte-specific PI3K gamma and PI3K
      delta isoforms of PI3K in PAF-induced chemotaxis of human eosinophils. METHODS:
      Chemotactic responses of the EoL-1 eosinophilic cell line and human peripheral
      blood eosinophils were measured. The effects of a PI3K gamma-selective inhibitor
      (5-[2,2-difluorobenzo(1,3)dioxol-5-ylmethylene]-thiazolidine-2,4-dione; AS604850)
      and gene knock-down of PI3K gamma and PI3K delta on chemotactic responses were
      determined. RESULTS: AS604850 caused a concentration-dependent suppression of
      chemotactic responses of EoL-1 cells and blood eosinophils to PAF but not
      eotaxin. Specific siRNAs reduced the expression of PI3K gamma and PI3K delta in
      EoL-1 cells. Knock-down of PI3K gamma by siRNA resulted in a 75% inhibition of
      the chemotactic response to PAF but had no effect on the response to eotaxin.
      Knock-down of endogenous PI3K delta by siRNA resulted in a 38% inhibition of the
      chemotactic response to PAF but had no effect on the response to eotaxin.
      CONCLUSION: PI3K gamma plays a major role in the induction of chemotaxis in PAF
      stimulated eosinophils, while PI3K delta plays a lesser role. Interventions which
      reduce the activity of PI3K gamma may have therapeutic potential in allergic
      diseases.

PMID- 20685405
TI  - Osteopenia and endothelin-1-mediated vasconstrictor tone in postmenopausal women.
AB  - Low bone mineral density is highly prevalent in postmenopausal women. Osteopenia
      in postmenopausal women is a predictor of adverse cardiovascular events. A
      potential mechanism contributing to the increased cardiovascular risk in
      postmenopausal women with osteopenia is endothelial vasomotor dysfunction.
      Endothelin (ET)-1 is a potent vasoconstrictor peptide that is associated with
      endothelial vasomotor dysfunction and increased cardiovascular risk. Currently,
      there is no information on osteopenia and ET-1 vasoconstrictor activity in
      postmenopausal women. We tested the hypothesis that ET-1 mediated vasoconstrictor
      activity is greater in postmenopausal women with osteopenia compared with those
      without. Forearm blood flow responses to intra-arterial infusion of BQ-123 (100
      nmol/min for 60 min), a selective ET(A) receptor antagonist, were determined in
      postmenopausal women: 10 with osteopenia (age: 56+/-1 yr, lumbar spine T-score
      between -1.5 and -2.5) and 12 without osteopenia (age: 60+/-2 yr, T-score>-1.5).
      In women with osteopenia, forearm blood flow increased approximately 25% (P<0.05)
      in response to BQ-123. However, in the women without osteopenia, resting forearm
      blood flow was not significantly changed. In conclusion, these results suggest
      that osteopenia is associated with greater ET-1-mediated vasoconstrictor tone.
      Increased ET-1 vasoconstrictor activity may contribute to the elevated
      cardiovascular risk in postmenopausal women with osteopenia.

PMID- 20685407
TI  - Pulmonary Hydatid Disease: Capitonnage is mandatory following Cystotomy.
AB  - Pulmonary hydatid disease still remains an important healthcare problem.
      Conservative operative interventions including cystotomy or cystotomy with
      capitonnage are the two commonly used techniques. There is still significant
      controversy, however, over selection of these two procedures. In this
      retrospective analysis of 66 patients with hydatid disease, we employed three
      types of interventions, Group A, (n=5) cystotomy alone with closure of bronchial
      openings; Group B, (n=54) cystotomy with capitonnage and Group C, (n=7) lobectomy
      over a period of seven years in our patients and compared their postoperative
      outcome in terms of morbidity and mortality. Our data show that cystotomy with
      capitonnage is associated with low rates of postoperative prolonged air leak,
      bronchopleural fistula formation, empyema formation [mean complication rate 0.12%
      (Mean 0.08; 0.151- 95% CI)] as compared to cystotomy alone with closure of
      bronchial openings [mean complication rate 44% (Mean 2.20; 3.18- 95% CI)]. The
      lobectomy group was excluded from the comparison, as this approach is quite
      different from the cystostomy based enucleation techniques. We conclude that
      capitonnage with cystotomy may be a preferred procedure due to its lower rate of
      complications.

PMID- 20685406
TI  - Longitudinal live animal micro-CT allows for quantitative analysis of tumor
      induced bone destruction.
AB  - The majority of breast cancer and prostate cancer patients with metastatic
      disease will go on to develop bone metastases, which contribute largely to the
      patient's morbidity and mortality. Numerous small animal models of cancer
      metastasis to bone have been developed to study tumor-induced bone destruction,
      but the advancement of imaging modalities utilized for these models has lagged
      significantly behind clinical imaging. Therefore, there is a significant need for
      improvements to live small animal imaging, particularly when obtaining high
      resolution images for longitudinal quantitative analyses. Recently, live animal
      micro-computed tomography (MUCT) has gained popularity due to its ability to
      obtain high-resolution 3-dimensional images. However, the utility of MUCT in bone
      metastasis models has been limited to end-point analyses due to off-target
      radiation effects on tumor cells. We hypothesized that live animal in vivo MUCT
      can be utilized to perform reproducible and quantitative longitudinal analyses of
      bone volume in tumor-bearing mice, particularly in a drug treatment model of
      breast cancer metastasis to bone. To test this hypothesis, we utilized the MDA-MB
      231 osteolytic breast cancer model in which the tumor cells are inoculated
      directly into the tibia of athymic nude mice and imaged mice weekly by Faxitron
      (radiography), Imtek MUCT (in vivo), and Maestro (GFP-imaging). Exvivo MUCT and
      histology were performed at end point for validation. After establishing a high
      resolution scanning protocol for the Imtek CT, we determined whether clear,
      measurable differences in bone volume were detectable in mice undergoing
      bisphosphonate drug treatments. We found that in vivo MUCT could be used to
      obtain quantifiable and longitudinal images of the progression of bone
      destruction over time without altering tumor cell growth. In addition, we found
      that we could detect lesions as early as week 1 and that this approach could be
      used to monitor the effect of drug treatment on bone. Taken together, these data
      indicate that in vivo MUCT is an effective and reproducible method for
      longitudinal monitoring of tumor-associated bone destruction in mouse models of
      tumor-induced bone disease.

PMID- 20685408
TI  - Is there a role for pre-operative thrombocytosis in the management of colorectal
      cancer?
AB  - BACKGROUND: High circulating platelet counts have been associated with poor
      prognosis in a variety of solid tumours such as breast, renal and lung cancer. We
      investigated the significance of a high pre-operative platelet count on overall
      survival in patients with stages I-IV colorectal cancer. PATIENTS AND METHODS:
      630 Consecutive patients who colorectal cancer resection between 2004 and 2007
      with a full blood count taken 14 days prior to the surgery were assessed.
      Male:female 7:5, median (range) age 73 (40-99 years). Thrombocytosis was defined
      as platelet count of >=450 * 10(9)/L. The relationship between platelet count,
      pathological features and overall survival was assessed. RESULTS: : Mantel-Cox
      regression showed that platelet count does not predict survival on multivariate
      analysis (p = 0.067). Thrombocytosis was present in 51/627 (8.1%) of cases. There
      was no statistically significant difference in mean survival (p = 0.067) observed
      in patients with platelet count <450 * 10(9)/L (n = 576; 95%CI: 1550.5-1405.4 SE
      37.0) versus >=450 * 10(9)/L (n = 51, CI: 1261.6-955.0, SE 78.2). There was also
      no correlation between Dukes stage and thrombocytosis. CONCLUSION(S): In our
      study, pre-operative thrombocytosis is not a prognostic indicator of survival in
      colorectal cancer patients regardless of pathological stage.

PMID- 20685409
TI  - A review on applications of chemiluminescence detection in food analysis.
AB  - There is an increasing interest by consumers for high quality food products with
      a specified composition. Suitable analytical techniques are needed for the
      quality control. Chemiluminescence (CL) detection has become quite a useful tool
      in the last years due to its simplicity, low cost and high sensitivity. Moreover,
      no external light source is needed. CL is often described as a dark-field
      technique: the absence of strong background light level reduces the background
      signal and leads to improved detection limits. Due to these advantages, CL
      methods have been widely applied to food analysis in recent years. Navas and
      Jimenez had reviewed the CL methods in food analysis in 1996. The present review
      covers the papers since 1996, including the CL determinations of nitrogen
      containing components, sugars, chemical preservatives, metals, hormonal anabolics
      and metabolites, and other compounds in foods. 122 references have been cited.

PMID- 20685410
TI  - Alpha/beta pulse shape discrimination in plastic scintillation using commercial
      scintillation detectors.
AB  - Activity determination in different types of samples is a current need in many
      different fields. Simultaneously analysing alpha and beta emitters is now a
      routine option when using liquid scintillation (LS) and pulse shape
      discrimination. However, LS has an important drawback, the generation of mixed
      waste. Recently, several studies have shown the capability of plastic
      scintillation (PS) as an alternative to LS, but no research has been carried out
      to determine its capability for alpha/beta discrimination. The objective of this
      study was to evaluate the capability of PS to discriminate alpha/beta emitters on
      the basis of pulse shape analysis (PSA). The results obtained show that PS pulses
      had lower energy than LS pulses. As a consequence, a lower detection efficiency,
      a shift to lower energies and a better discrimination of beta and a worst
      discrimination of alpha disintegrations was observed for PS. Colour quenching
      also produced a decrease in the energy of the particles, as well as the effects
      described above. It is clear that in PS, the discrimination capability was
      correlated with the energy of the particles detected. Taking into account the
      discrimination capabilities of PS, a protocol for the measurement and the
      calculation of alpha and beta activities in mixtures using PS and commercial
      scintillation detectors has been proposed. The new protocol was applied to the
      quantification of spiked river water samples containing a pair of radionuclides
      ((3)H-(241)Am or (90)Sr/(90)Y-(241)Am) in different activity proportions. The
      relative errors in all determinations were lower than 7%. These results
      demonstrate the capability of PS to discriminate alpha/beta emitters on the basis
      of pulse shape and to quantify mixtures without generating mixed waste.

PMID- 20685411
TI  - Speciation and determination of ultra trace amounts of inorganic tellurium in
      environmental water samples by dispersive liquid-liquid microextraction and
      electrothermal atomic absorption spectrometry.
AB  - A simple and powerful method has been developed for the rapid and selective
      determination of Te(IV) and Te(VI), employing dispersive liquid-liquid
      microextraction combined with electrothermal atomic absorption spectrometry using
      palladium as permanent modifier. Under acidic conditions pH 1, only Te(IV) can
      form a complex with ammonium pyrrolidine dithiocarbamate (APDC) and therefore be
      extracted into fine droplets of carbon tetrachloride (extraction solvent) which
      are dispersed with ethanol into the water sample solution. After centrifugation,
      Te(IV) was determined in the sedimented organic phase while Te(VI) remained in
      the aqueous phase. Total inorganic tellurium was determined after the reduction
      of the Te(VI) to Te(IV). Te(VI) was calculated as the difference between the
      measured total inorganic tellurium and Te(IV) content. The effective parameters
      for improving the efficiency of microextraction process were investigated by
      using experimental and central composite designs. Under optimal conditions the
      enrichment factor was 125 and the calibration graph was linear in the range of
      0.015-1 ng mL(-1) with detection limit and characteristic mass of 0.004 ng mL(-1)
      and 0.033 pg, respectively. The relative standard deviation for 0.5 ng mL(-1) of
      tellurium measurement was 3.6% (n=6) at ash and atomization temperature, 900 and
      2600 degrees C, respectively. The recoveries of spiked Te(IV) and Te(VI) to the
      environmental water samples were 89.6-101.3% and 96.6-99.1%, respectively. The
      accuracy is also evaluated by applying the proposed method to certified reference
      material (NIST SRM 1643e), for which the result was in a good agreement with the
      certified values reported for this CRM (95% confidence level).

PMID- 20685412
TI  - The dissociation kinetics of Cu-dissolved organic matter complexes from soil and
      soil amendments.
AB  - Complexes between dissolved organic matter (DOM) and copper (Cu) that dissociate
      very slowly can theoretically facilitate Cu leaching to the groundwater. Data on
      dissociation kinetics of Cu-DOM complexes present in soil and in soil amendments
      are limited. The dissociation kinetics of different Cu-DOM complexes from soil,
      wastewater, pig manure and sewage sludge was measured with the Competitive Ligand
      Exchange Method (CLEM) and Diffusive Gradient in Thin films (DGT) technique. The
      solutions were set at constant pH, Ca concentration and free Cu(2+) activity to
      allow comparison between the different samples. The average dissociation rate
      constant k(d) of the complexes, as measured by CLEM, was about 10(-3) s(-1) and
      the fractions of dissolved Cu that were undissociated after 8 h ranged from <1%
      to 25%. These fractions determined by CLEM were significantly correlated with the
      non-labile fractions (0-82%) determined in the DGT tests and data analysis show
      that DGT data can be predicted from CLEM data. The dissociation rates decreased
      when Cu-DOM complexes had been equilibrated at lower Cu(2+) activities.
      Increasing the Cu-DOM contact time (7-297 days) decreased the dissociation rate.
      The non-labile fractions were positively correlated with the specific UV
      absorbance suggesting that aromatic moieties in DOM hold non-labile Cu. All
      natural Cu-DOM complexes contained a detectable fraction with a dissociation rate
      constant k(d) lower than 10(-5)s(-1) which can theoretically lead to non
      equilibrium conditions and leaching risks in soil.

PMID- 20685413
TI  - Use of constrained mixture design for optimization of method for determination of
      zinc and manganese in tea leaves employing slurry sampling.
AB  - A slurry suspension sampling technique has been developed for manganese and zinc
      determination in tea leaves by using flame atomic absorption spectrometry. The
      proportions of liquid-phase of the slurries composed by HCl, HNO(3) and Triton X
      100 solutions have been optimized applying a constrained mixture design. The
      optimized conditions were 200mg of sample ground in a tungsten carbide balls mill
      (particle size<100 microm), dilution in a liquid-phase composed by 2.0 mol L(-1)
      nitric, 2.0 mol L(-1) hydrochloric acid and 2.5% Triton X-100 solutions (in the
      proportions of 50%, 12% and 38% respectively), sonication time of 10 min and
      final slurry volume of 50.0 mL. This method allowed the determination of
      manganese and zinc by FAAS, with detection limits of 0.46 and 0.66 microg g(-1),
      respectively. The precisions, expressed as relative standard deviation (RSD), are
      6.9 and 5.5% (n=10), for concentrations of manganese and zinc of 20 and 40 microg
      g(-1), respectively. The accuracy of the method was confirmed by analysis of the
      certified apple leaves (NIST 1515) and spinach leaves (NIST 1570a). The proposed
      method was applied for the determination of manganese and zinc in tea leaves used
      for the preparation of infusions. The obtained concentrations varied between 42
      and 118 microg g(-1) and 18.6 and 90 microg g(-1), respectively, for manganese
      and zinc. The results were compared with those obtained by an acid digestion
      procedure and determination of the elements by FAAS. There was no significant
      difference between the results obtained by the two methods based on a paired t
      test (at 95% confidence level).

PMID- 20685414
TI  - Micro near infrared spectroscopy (MicroNIRS) based on on-line enrichment:
      determination of trace copper in water using glycidyl methacrylate-based
      monolithic material.
AB  - A micro near infrared spectroscopy (MicroNIRS) technique based on monolithic
      column enrichment has been developed to detect low concentration metallic ions in
      water. Glycidyl methacrylate-ethylene dimethacrylate-iminodiacetic acid (GMA-EDMA
      IDA) monolithic material was synthesized to construct an enrichment device, which
      can enrich metallic ions more efficiently than chelating resin materials such as
      D401. Cu(2+) solutions passed through the enrichment device and concentrated on
      the surface of the material, and then diffuse reflection NIR (DRNIR) spectra were
      measured by touching the NIR probe on the surface. The spectra were pretreated
      with multiplicative scatter correction (MSC) and the MSC-pretreated spectra
      showed high linear correlation to the Cu(2+) concentrations in spectral regions
      of 900-1350 nm, 1420-1480 nm and 1970-2050 nm for all concentration ranges. PLS
      models built with leave-one-out cross-validation also yielded good features. The
      mean relative error (MRE) of prediction was 10.0% in the 0.0001-0.0010 microg mL(
      1) range. The concentration has low to ppb-level, but the MRE was not more than
      10%, which was acceptable for trace analysis. The results revealed that the
      MicroNIRS technique enhanced the sensitivity of NIRS dramatically and widened the
      NIRS technique to micro and trace analysis field.

PMID- 20685415
TI  - Simultaneous chemiluminescence determination of amoxicillin and clavulanic acid
      using least squares support vector regression.
AB  - In this work, both the batch and flow injection chemiluminescence (CL) methods
      have been proposed for the simultaneous determination of two structurally similar
      beta-lactams including amoxicillin and clavulanic acid (CLAV). Chemiluminescence
      spectral overlap of these two structurally similar beta-lactams is the main
      limitation for the simultaneous analysis of the two compounds. Least squares
      support vector regression (LS-SVR) was applied to relate concentration of both
      the compounds to their CL profiles. The parameters of the model, consisting of
      kernel parameter, sigma(2), and the regularization parameter, gamma, were
      optimized by constructing different LS-SVR models and the model with the minimum
      root mean squared error of cross-validation (RMSECV) for the calibration set was
      selected as the best model and its parameters were chosen as the optimized
      values. The performance of LS-SVR model was compared with Partial Least Squares
      (PLS) and the results revealed the superiority of the LS-SVR over PLS model.
      Under the optimized experimental conditions for both the compounds, when LS-SVR
      was applied, the detection limits obtained were 0.2 and 0.60 micromol L(-1) in
      the batch mode and 0.3 and 0.5 micromol L(-1) in the flow injection mode for CLAV
      and amoxicillin, respectively. The proposed method was utilized for the
      simultaneous determination of the compounds in pharmaceutical formulations and
      spiked plasma samples.

PMID- 20685416
TI  - Direct electrochemistry and electrocatalysis of horseradish peroxidase with
      hyaluronic acid-ionic liquid-cadmium sulfide nanorod composite material.
AB  - A new composite material consisted of hyaluronic acid (HA), ionic liquid 1-butyl
      3-methylimidazolium tetrafluoroborate ([BMIM]BF(4)) and cadmium sulfide (CdS)
      nanorod was fabricated and used for the immobilization of horseradish peroxidase
      (HRP) on the surface of a carbon ionic liquid electrode (CILE), which was
      prepared with 1-ethyl-3-methyl-imidazolium ethylsulphate ([EMIM]EtOSO(3)) as
      modifier. Spectroscopic results indicated that HRP remained its native structure
      in the composite film. Based on the synergistic effect of the materials used, an
      obvious promotion to the direct electron transfer efficient between HRP and CILE
      was achieved with a pair of well-defined redox peaks appeared in 0.1 mol L(-1)
      phosphate buffer solution, indicating the realization of the direct
      electrochemistry of HRP. The immobilized HRP showed good electrocatalytic
      activity towards the reduction of trichloroacetic acid and H(2)O(2) with the
      electrochemical parameters calculated. Based on the fabricated electrode, a new
      third-generation electrochemical biosensor was constructed with good stability
      and reproducibility.

PMID- 20685417
TI  - Electrochemical biosensor for the detection of H2O2 from living cancer cells
      based on ZnO nanosheets.
AB  - In this work, direct electron transfer of cytochrome c (cyt. c)--a model for
      studying the electron transfer of enzymes is achieved at hexagonal ZnO nanosheets
      by one-step electrodeposition. UV-vis spectra and electrochemical data
      demonstrate that such ZnO nanosheets can supply a bio-compatible surface to keep
      the bioactivity of cyt. c. The redox formal potential (E(0)') of cyt. c is
      estimated to be 338.2+/-4.3 mV (vs. AgAgCl) at the nanostructured ZnO surface.
      This value is much more positive than those of enzymes previously obtained at
      other metal oxides and zeolite surfaces. Experiment data show, under the
      optimized potential of 0.0 V (vs. AgAgCl), the electrochemical determination of
      H(2)O(2) is free from not only anodic interferences like ascorbic acid (AA) and
      dopamine (DA), but also a cathodic interference-O(2). Such an excellent
      selectivity enable the present H(2)O(2) biosensor determine the extracellular
      H(2)O(2) released from living human hepatoma cells.

PMID- 20685418
TI  - Validation of an analytical method for analysis of cannabinoids in hair by
      headspace solid-phase microextraction and gas chromatography-ion trap tandem mass
      spectrometry.
AB  - The development of an analytical method for the determination of Delta(9)
      tetrahydrocannabinol (THC), cannabidiol (CBD) and cannabinol (CBN) in samples of
      human hair is described. Samples were subjected to a procedure based on the
      combination of headspace solid-phase microextraction (HS-SPME) with gas
      chromatography linked with mass spectrometry operating in tandem mode (GC-MS/MS).
      A 10 mg aliquot of sample was firstly decontaminated using petroleum ether,
      deionized water and dichloromethane (2 mL of each solvent), for 10 min under
      sonication, and then digested in alkaline solution (1 mol L(-1) NaOH). The method
      variables evaluated were pH, mass of hair, fiber type, extraction temperature,
      desorption time, ionic strength, pre-equilibrium time and extraction time.
      Parameters concerning operation of the tandem mode MS/MS were also assessed and
      optimized. Validation of the method demonstrated excellent linearity in the range
      0.1-8.0 ng mg(-1), with regression coefficients better than 0.994. Precision was
      determined using two different concentrations (upper and lower limits of the
      linear range), and RSD values were between 6.6 and 16.4%. Absolute recoveries
      (measured in triplicate) were in the range 1.1-8.7%, and limits of detection and
      quantification were 0.007-0.031 ng mg(-1) and 0.012-0.062 ng mg(-1),
      respectively. The LOQ for THC (0.062 ng mg(-1)) was below the cut-off value (LOQ
      < or = 0.1 ng mg(-1)) established by the Society of Hair Testing (SOHT), the
      Society of Toxicological and Forensic Chemistry (STFCh) and the Societe Francaise
      de Toxicologie Analytique (SFTA). The optimized SPME method was applied in
      analysis of hair samples from Cannabis drug users, showing that CBN and CBD were
      present in all samples analyzed.

PMID- 20685419
TI  - Selective enrichment and determination of nicosulfuron in water and soil by a
      stir bar based on molecularly imprinted polymer coatings.
AB  - A new molecularly imprinted stir bar was prepared using nicosulfuron, a
      sulfonylurea herbicide, as a template. To achieve the selective and direct
      extraction of a target analyte from aqueous samples, several main parameters,
      including extraction time, pH value and contents of inorganic salt in the sample
      matrix, were investigated. Competitive sorption experiments showed that using six
      sulfonylureas as substrates the imprinted stir bar gave high selectivity and
      imprinted effect on the template nicosulfuron in comparison with the non
      imprinted stir bar. Evidence was also presented by the scanning electronic
      microscopic images of the imprinted and non-imprinted stir bars. This resulted in
      a combined imprinted stir bar-HPLC-UV method allowing the determination of trace
      nicosulfuron from the sample matrix. Based on a signal to noise ratio of 3, the
      detection limits were 0.75 nM for the tap water and 12.0 nmol kg(-1) for the
      soil. The method showed good recoveries and precision, 93.4% (RSD 1.5%, n=3) for
      100 mL of tap water spiked with 2.0 nmol and 81.3% (RSD 2.6%, n=3) for 10 g of
      soil spiked with 0.80 nmol, suggesting that the imprinted stir bar can be
      successfully applied to the preconcentration of nicosulfuron in real samples.

PMID- 20685420
TI  - Analytical particle measurements in an optical microflume.
AB  - In this work, microscopic particles in a fluid flow are manipulated using forces
      generated by a high power laser beam. The resulting manipulations on the
      particles are imaged using a microscope lens connected to a CCD camera.
      Differential forces on particles of varying physical and chemical composition
      have been measured. The goal is to measure the optical forces on a diverse range
      of particles and catalog the associated chemical and physical differences to
      understand which properties and mechanisms result in the largest force
      differentials. Using these measurements our aim is to better understand
      differences between similar microspheres in terms of size, morphology, or
      chemical composition. Particles of the same size, but different composition show
      large variations in optical pressure forces and are easily discernable in the
      present analytical system. In addition, we have demonstrated the ability to
      differentiate a 70 nm size difference between two NIST precision size standard
      polystyrene microspheres, corresponding to a 2.0 pN difference in optical force.
      Lastly, the instrument was used to measure differences between biological samples
      of similar size, demonstrating the ability to make precise analytical
      measurements on microorganism samples.

PMID- 20685421
TI  - Simultaneous determination of plasma epinephrine and norepinephrine using an
      integrated strategy of a fully automated protein precipitation technique,
      reductive ethylation labeling and UPLC-MS/MS.
AB  - A novel, automated, simple, sensitive, specific, accurate, precise and high
      throughput liquid chromatography tandem mass spectrometry (LC-MS/MS)-based method
      has been developed for simultaneous determination of epinephrine (E) and
      norepinephrine (NE) in plasma by using the combination of a fully automated
      protein precipitation technique for plasma sample preparation, reductive
      ethylation labeling with UPLC-MS/MS. A simple protein precipitation procedure was
      used to clean up 50 microL calibration samples prepared in stripped human plasma
      and 50 microL quality control plasma samples containing 25 microL plasma and 25
      microL stabilizing additives. The supernatants were subsequently dried down and
      then reconstituted with commercially available and cost-effective reductive
      ethylation labeling reagents, followed by UPLC-MS/MS analysis. All liquid
      handling during sample preparation was automated using a Hamilton MicroLab Star
      Robotic workstation, which included the preparation of standards and quality
      control samples, shaking of 96-well plates, adding and transferring liquids.
      Processing time, which included the preparation of standards and quality control
      samples, protein precipitation and reductive ethylation labeling, is less than 2
      h per 96-well plate. The chromatographic run time is 3.5 min per sample. The
      limits of detection of UPLC-MS/MS-based methods for E and NE, with/without
      reductive ethylation labeling, are 0.025/0.40 and 0.025/2.00 ng mL(-1),
      respectively. Reductive ethylation labeling of amino groups of E and NE affords
      16 and 80 times increased detection sensitivity of corresponding native
      counterparts during the UPLC-MS/MS analysis. The linearity of this method was
      established from 0.05 to 25 ng mL(-1) for E and NE with accuracy and precision
      within 15% at all concentrations. The intra-run and inter-run assay accuracy
      (%RE) and coefficient of variations (CV%) are all within 15% for all QC samples
      prepared in commercially purchased plasma samples.

PMID- 20685422
TI  - A low cost short wave near infrared spectrophotometer: application for
      determination of quality parameters of diesel fuel.
AB  - A low cost absorption spectrophotometer for the short wave near infrared spectral
      region (850-1050 nm) is described. The spectrophotometer is basically composed of
      a conventional dichroic lamp, a long-pass filter, a sample cell and a Czerny
      Turner type polychromator coupled to a 1024 pixel non-cooled photodiode array. A
      preliminary evaluation of the spectrophotometer showed good repeatability of the
      first derivative of the spectra at a constant room temperature and the
      possibility of assigning some spectral regions to different C-H stretching third
      overtones. Finally, the spectrophotometer was successfully applied for the
      analysis of diesel samples and the determination of some of their quality
      parameters using partial least squares calibration models. The values found for
      the root mean square error of prediction using external validation were 0.5 for
      the cetane index and from 2.5 to 5.0 degrees C for the temperatures achieved
      during distillation when obtaining 10, 50, 85, and 90% (v/v) of the distilled
      sample, respectively.

PMID- 20685426
TI  - [Solution to case 17. Primitive neuroectodermal tumor of the chest wall].

PMID- 20685427
TI  - [Solution to case 18: Hydrocele of the canal of Nuck].

PMID- 20685428
TI  - Pre-analytical and methodological challenges in red blood cell microparticle
      proteomics.
AB  - Microparticles are phospholipid vesicles shed mostly in biological fluids, such
      as blood or urine, by various types of cells, such as red blood cells (RBCs),
      platelets, lymphocytes, endothelial cells. These microparticles contain a subset
      of the proteome of their parent cell, and their ready availability in biological
      fluid has raised strong interest in their study, as they might be markers of cell
      damage. However, their small size as well as their particular physico-chemical
      properties makes them hard to detect, size, count and study by proteome analysis.
      In this review, we report the pre-analytical and methodological caveats that we
      have faced in our own research about red blood cell microparticles in the context
      of transfusion science, as well as examples from the literature on the proteomics
      of various kinds of microparticles.

PMID- 20685429
TI  - Occurrence and chemical speciation analysis of organotin compounds in the
      environment: a review.
AB  - Environmental concerns regarding organotin compounds have increased remarkably in
      the past 20 years, due in large part to the use of these compounds as active
      components in antifouling paints [mainly tributyltin (TBT)] and pesticide
      formulations [mainly triphenyltin (TPhT)]. Their direct introduction into the
      environment, their bio-accumulation and the high toxicity of these compounds
      towards "non-target" organisms (for example: oysters and mussels) causes
      environmental and economic damage around the world. As a consequence, the
      presence and absence of organotin compounds is currently monitored in a range of
      environmental matrices (e.g., water, sediment and shellfish) to examine the
      utility of controls meant to regulate the level of contamination as required in
      some EC Directives and the Water Framework Directive 2000/60/EC. To evaluate the
      environmental distribution and fate of these compounds and to determine the
      effectives of legal provisions adopted by a number of countries, a variety of
      analytical methods have been developed for organotin determination in the
      environment. Most of these methods include different steps such as extraction,
      derivatisation and clean up. The aim of the present review is to evaluate the
      environmental distribution, fate and chemical speciation of organotin compounds
      in the environment.

PMID- 20685430
TI  - A highly sensitive non-enzymatic glucose sensor based on a simple two-step
      electrodeposition of cupric oxide (CuO) nanoparticles onto multi-walled carbon
      nanotube arrays.
AB  - A novel, stable and highly sensitive non-enzymatic glucose (Glc) sensor was
      developed using vertically well-aligned multi-walled carbon nanotubes array
      (MWCNTs) incorporated with cupric oxide (CuO) nanoparticles. The MWCNTs array was
      prepared by catalytic chemical vapor deposition on a tantalum (Ta) substrate,
      while a simple and rapid two-step electrodeposition technique was used to prepare
      the CuO-MWCNTs nanocomposite. First, Cu nanoparticles were deposited onto MWCNTs
      at constant potential and then they were oxidized into CuO by potential cycling.
      The electrocatalytic activity of CuO-MWCNTs array was investigated for Glc under
      alkaline conditions using cyclic voltammetry and chronoamperometry. The sensor
      exhibited a linear response up to 3 mM of Glc and sensitivity of 2190 microA mM(
      1) cm(-2), which is two to three orders of magnitude higher than that of most non
      enzymatic Glc sensors reported in the literature. The sensor response time is
      less than 2s and detection limit is 800 nM (at signal/noise=3). When tested with
      human blood serum samples, the sensor exhibited high electrocatalytic activity,
      stability, fast response and good selectivity against common interfering species,
      suggesting its potential to be developed as a non-enzymatic Glc sensor.

PMID- 20685431
TI  - Amperometric lactate biosensor for flow injection analysis based on a screen
      printed carbon electrode containing Meldola's Blue-Reinecke salt, coated with
      lactate dehydrogenase and NAD+.
AB  - A biosensor for the measurement of lactate in serum has been developed, which is
      based on a screen-printed carbon electrode, modified with Meldola's Blue-Reinecke
      Salt (MBRS-SPCE), coated with the enzyme lactate dehydrogenase NAD(+) dependent
      (from Porcine heart), and NAD(+). A cellulose acetate layer was deposited on the
      top of the device to act as a permselective membrane. The biosensor was
      incorporated into a commercially available, thin-layer, amperometric flow cell
      operated at a potential of only +0.05 V vs. Ag/AgCl. The mobile phase consisted
      of 0.2 M phosphate buffer pH 10 containing 0.1 M potassium chloride solution; a
      flow rate of 0.8 ml min(-1) was used throughout the investigation. The biosensor
      response was linear over the range 0.55-10 mM lactate; the former represents the
      detection limit. The precision of the system was determined by carrying out 10
      repeat injections of 10 mM l(+)lactic acid standard; the calculated coefficient
      of variation was 4.28%. It was demonstrated that this biosensor system could be
      applied to the direct measurement of lactate in serum without pre-treatment;
      therefore, this would allow high throughput-analysis, at low cost, for this
      clinically important analyte.

PMID- 20685432
TI  - Detection of arsenic-containing hydrocarbons in canned cod liver tissue.
AB  - Arsenic is a metalloid well known to be potentially toxic depending of its
      species. Lipid-soluble arsenicals (arsenolipids) are present in a wide range of
      biological samples in which they could play a role in the biosynthesis of
      organoarsenic compounds from inorganic arsenic compounds. Arsenolipids have
      recently attracted considerable interest. In order to gain deeper insights into
      the impact of arsenolipids new analytical approaches for reliable determination
      of this class of arsenic-containing hydrocarbons in various matrices are needed.
      High concentrations of arsenolipids were found in seafood which served as sample
      material in this study. We report the investigation of three arsenolipids found
      in canned cod liver from which they were extracted and purified by solid phase
      extraction (SPE) using a silica gel column and ethyl acetate/methanol as eluent.
      Analytical studies were conducted by means of gas chromatography coupled with ICP
      MS, MIP-AES and EI-qMS and by TOF-MS. The results obtained by GC-ICP-MS and GC
      MIP-AES showed the existence of numerous arsenic compounds in the SPE fractions
      collected. Three major peaks were found within a retention time window between 10
      and 25 min. The presence of arsenic compounds in the fish tissue could be
      confirmed using GC-EI-qMS analysis. Corresponding information of the molecular
      weights of the major arsenic species were provided by TOF-MS which allows highly
      accurate mass determinations. The results showed the presence of the arsenic
      containing hydrocarbons with the following molecular formulas: C(17)H(37)AsO
      (calculated for [M+H](+) 333.2133; found 333.2136; Deltam=0.90 ppm);
      C(19)H(41)AsO (calculated for [M+H](+) 361.2446; found 361.2446; Deltam=0.00
      ppm); C(23)H(37)AsO (calculated for [M+H](+) 405.2133; found 405.2145;
      Deltam=2.96 ppm). Suggestions for the corresponding structures are discussed.

PMID- 20685433
TI  - Comparative study on 2-amino-1,4-naphthoquinone derived ligands as indium (III)
      selective PVC-based sensors.
AB  - The three different ligands (Q(2) to Q(4)) based on 2-amino-1,4-naphthoquinone
      (Q(1)), have been synthesized and explored as neutral ionophores for preparing
      polyvinyl chloride-based membrane sensors selective to indium (III). The addition
      of potassium tetrakis(4-chlorophenyl) borate and various plasticizers, viz., o
      NPOE, DBP, DBBP, DOP and CN has been found to substantially improve the
      performance of the sensors. The best performance was obtained with the sensor no.
      16 having membrane of ligand (Q(2)) with composition (%, w/w) ionophore Q(2)
      (3.0%):PVC (30.0%):o-NPOE (63.0%):KTpClPB (4.0%). This sensor exhibits Nernstian
      response with slope 19.8 mV/decade of activity in the concentration range 2.5 x
      10(-7) to 1.0 x 10(-2) M indium (III), performs satisfactorily over wide pH range
      of (2.5-7.5) with a fast response time (10 s). The sensor was also found to work
      satisfactorily in partially non-aqueous media up to 20% (v/v) content of
      acetonitrile, ethanol and methanol. The proposed sensor can be used over a period
      of 3.5 months without significant drift in potentials. The quantitative
      application of sensor was also evaluated by comparative analysis of artificially
      made sea water with AAS.

PMID- 20685434
TI  - Detection of Newcastle disease virus with quantum dots-resonance light scattering
      system.
AB  - A sensitive QDs-based RLS assay method for the detection of Newcastle disease
      virus (NDV) antibody has been developed. CdTe quantum dots (QDs) were conjugated
      with Newcastle disease virus and used as RLS-based probes to detect NDV antibody.
      The electrostatic interaction between CdTe QDs and NDV resulted in enhanced
      resonance light scattering (RLS) signal characterized at 555 nm. Upon the
      addition of NDV antibody, QDs-NDV formed dispersive immunocomplex that can
      decrease the RLS signal. The decreased RLS intensity at 555 nm (DeltaI(RLS)) was
      linearly proportional to the concentration of NDV antibody (C(anti-NDV)) in the
      range of 0.5-50 ng/mL, with correlation coefficient of 0.974 and detection limit
      of 0.1 ng/mL under the optimization conditions. The proposed method was applied
      to the determination of NDV antibody in spiked samples with satisfactory results.

PMID- 20685435
TI  - Polymeric ionic liquid as additive for the high speed and efficient separation of
      aromatic acids by co-electroosmotic capillary electrophoresis.
AB  - A simple and reliable co-electroosmotic capillary electrophoresis system for the
      fast determination of aromatic acids has been developed by employing poly (1
      vinyl-3-butylimidazolium bromide) as the background electrolyte modifier. The
      polymeric ionic liquid was synthesized by the conventional radical
      polymerization. The reversed electroosmotic flow was obtained by adding a small
      amount of the polymeric ionic liquid (0.0006%, w/v) to the electrolyte. To
      further improve the resolution of aromatic acids, conditions including the
      concentration of polymeric ionic liquid and pH of background electrolytes were
      optimized. All eight aromatic acids were baseline resolved in one measurement in
      a short time (less than 3.5 min) under optimized conditions, 100 mM NaH(2)PO(4)
      buffer containing 0.006% (w/v) polymeric ionic liquid, pH 6.0. Separation
      efficiencies were in the range from 355,000 to 943,000 (plates/m). Satisfactory
      reproducibility on the basis of the migration time of analytes was achieved. RSDs
      (n=3) were less than 0.33% except the p-aminobenzoic acid (0.9%). The
      applicability of the present method has been demonstrated for the determination
      of water-soluble aromatic acids in a common drug for external use.

PMID- 20685436
TI  - Determination of beta-adrenergic agonists by hapten microarray.
AB  - The use of highly active beta-agonists as growth promoters is not appropriate
      because of the potential hazard for human and animal health. To investigate the
      residue level of these beta-agonists, hapten microarrays were employed for
      clenbuterol (CLB), ractopamine (RAC) and salbutamol (SAL) residue analysis. CLB,
      RAC and SAL conjugates were immobilized on the slides, which were precoated by
      agarose film to construct hapten microarrays, and then the corresponding
      monoclonal antibodies of these beta-agonists and the standards or samples were
      introduced for indirect competitive immunoassay. Finally, Cy3-labeled secondary
      antibody was employed to indicate the antigen-antibody complex. The fluorescence
      intensity of each spot was imaged and recorded, and the calibration curve of each
      analyte was obtained by plot fluorescence intensity against different standard
      concentrations. Compared to the ELISA, the hapten microarray method was more
      sensitive, which got the detection limits 0.09 microg/L for CLB, 0.50 microg/L
      for RAC, and 0.01 microg/L for SAL. What's more, with the recovery rate between
      96.5% and 106.4%, and the coefficient of variation below 10%, the proposed hapten
      microarray method was shown to be both quantitative and reproducible.

PMID- 20685437
TI  - Ultraviolet detection of amino acids based on their on-column conjugation with
      cupric cation using a disposable electrophoresis microdevice.
AB  - A method for fast sensitive ultraviolet detection of amino acids was developed
      with a disposable electrophoresis microdevice. The microdevice was conveniently
      constructed by fixing a fused-silica capillary with a sampling fracture to a
      printed circuit board. During the separation process, the on-column conjugation
      of amino acids with cupric cation led to the ultraviolet absorption at 232 nm
      that could be directly used for fast analysis of amino acids. Using 20 mM boric
      acid (pH 5.3) containing 5 mM cupric cation and 0.015% Tween 20 as running
      buffer, this method could completely separate lysine, glutamine and serine at a
      sampling time of 2 s at +210 V and a separation voltage of +1800 V (240 V/cm).
      The theoretical plate numbers were from 140,000 to 205,000 plates/m. The linear
      ranges were from 10 to 500 microM for lysine, 20-1000 microM for glutamine and
      serine. The novel protocol had been successfully used to detect amino acids in
      beverage samples with recovery more than 85.0%, indicating its advantages and
      potential analytical application in different fields.

PMID- 20685438
TI  - Microwave-accelerated derivatization for capillary electrophoresis with laser
      induced fluorescence detection: a case study for determination of histidine, 1-
      and 3-methylhistidine in human urine.
AB  - The feasibility of microwave-accelerated derivatization for capillary
      electrophoresis (CE) with laser-induced fluorescence (LIF) detection was
      evaluated. The derivatization reaction was performed in a domestic microwave
      oven. Histidine (His), 1-methylhistidine (1-MH) and 3-methylhistidine (3-MH) were
      selected as test analytes and fluorescein isothiocyanate (FITC) was chosen as a
      fluorescent derivatizing reagent. Parameters that may affect the derivatization
      reaction and/or subsequent CE separation were systematically investigated. Under
      optimized conditions, the microwave-accelerated derivatization reaction was
      successfully completed within 150 s, compared to 4-24 h in a conventional water
      bath derivatization process. This will remarkably reduce the overall analysis
      time and increase sample throughput of CE-LIF. The detection limits of this
      method were found to be 0.023 ng/mL for His, 0.023 ng/mL for 1-MH, and 0.034
      ng/mL for 3-MH, respectively, comparable to those obtained using traditional
      derivatization protocols. The proposed method was characterized in terms of
      precision, linearity, accuracy and successfully applied for rapid and sensitive
      determination of these analytes in human urine.

PMID- 20685439
TI  - Highly sensitive and selective spectrofluorimetric determination of
      metoclopramide hydrochloride in pharmaceutical tablets and serum samples using
      Eu3+ ion doped in sol-gel matrix.
AB  - A simple, sensitive and selective spectrofluorimetric method for the
      determination of Metoclopramide hydrochloride (MCP) is developed. The MCP can
      remarkably enhances the luminescence intensity of the Eu(3+) ion doped in sol-gel
      matrix at lambda(ex)=380 nm in DMSO at pH 8.7. The intensity of the emission band
      of Eu(3+) ion doped in sol-gel matrix increases due to energy transfer from MCP
      to Eu(3+) in the excited state. The enhancement of the emission band of Eu(3+)
      ion doped in sol-gel matrix at 617 nm was found to be directly proportional to
      the concentration of MCP with a dynamic range of 5 x 10(-9) - 1.0 x 10(-6) mol L(
      1) and detection limit of 2.2 x10(-11) mol L(-1).

PMID- 20685440
TI  - Nonenzymatic amperometric sensor of hydrogen peroxide and glucose based on Pt
      nanoparticles/ordered mesoporous carbon nanocomposite.
AB  - A simple and facile synthetic method to incorporate Pt nanoparticles inside the
      mesopores of ordered mesoporous carbons (OMCs) is reported. The Pt/OMCs
      nanocomposite was characterized by transmission electron microscopy (TEM), X-ray
      diffraction (XRD), X-ray photoelectron spectroscopy (XPS), Raman spectroscopy,
      and nitrogen adsorption-desorption. The results show that the incorporation of Pt
      nanoparticles inside the pores of OMCs does not change the highly ordered two
      dimensional hexagonal mesostructure of OMCs matrix. Nonenzymatic amperometric
      sensor of hydrogen peroxide and glucose based on the Pt/OMCs nanocomposite
      modified glassy carbon (GC) electrode is developed. Compared with the original
      OMCs-modified electrode, the Pt/OMCs-modified electrode displays improved current
      response towards hydrogen peroxide and gives linear range from 2 to 4212 microM.
      At an applied potential of -0.08 V, the Pt/OMCs nanocomposite gives linearity in
      the range of 0.5-4.5 mM glucose in neutral buffered saline solution. This glucose
      sensor also exhibits good ability of anti-interference to electroactive
      molecules. The combination the unique properties of Pt nanoparticles and the
      ordered mesostructure of OMCs matrix guarantees the enhanced response for
      hydrogen peroxide and glucose.

PMID- 20685441
TI  - Suitability of Tedlar gas sampling bags for siloxane quantification in landfill
      gas.
AB  - Landfill or digester gas can contain man-made volatile methylsiloxanes (VMS),
      usually in the range of a few milligrams per normal cubic metre (Nm(3)). Until
      now, no standard method for siloxane quantification exists and there is
      controversy with respect to which sampling procedure is most suitable. This paper
      presents an analytical and a sampling procedure for the quantification of common
      VMS in biogas via GC-MS and polyvinyl fluoride (Tedlar) bags. Two commercially
      available Tedlar bag models are studied. One is equipped with a polypropylene
      valve with integrated septum, the other with a dual port fitting made from
      stainless steel. Siloxane recovery in landfill gas samples is investigated as a
      function of storage time, temperature, surface-to-volume ratio and background
      gas. Recovery was found to depend on the type of fitting employed. The siloxanes
      sampled in the bag with the polypropylene valve show high and stable recovery,
      even after more than 30 days. Sufficiently low detection limits below 10 microg
      Nm(-3) and good reproducibility can be achieved. The method is therefore well
      applicable to biogas, greatly facilitating sampling in comparison with other
      common techniques involving siloxane enrichment using sorption media.

PMID- 20685442
TI  - Screening Brazilian commercial gasoline quality by hydrogen nuclear magnetic
      resonance spectroscopic fingerprintings and pattern-recognition multivariate
      chemometric analysis.
AB  - The identification of gasoline adulteration by organic solvents is not an easy
      task, because compounds that constitute the solvents are already in gasoline
      composition. In this work, the combination of Hydrogen Nuclear Magnetic Resonance
      ((1)H NMR) spectroscopic fingerprintings with pattern-recognition multivariate
      Soft Independent Modeling of Class Analogy (SIMCA) chemometric analysis provides
      an original and alternative approach to screening Brazilian commercial gasoline
      quality in a Monitoring Program for Quality Control of Automotive Fuels. SIMCA
      was performed on spectroscopic fingerprints to classify the quality of
      representative commercial gasoline samples selected by Hierarchical Cluster
      Analysis (HCA) and collected over a 6-month period from different gas stations in
      the Sao Paulo state, Brazil. Following optimized the (1)H NMR-SIMCA algorithm, it
      was possible to correctly classify 92.0% of commercial gasoline samples, which is
      considered acceptable. The chemometric method is recommended for routine
      applications in Quality-Control Monitoring Programs, since its measurements are
      fast and can be easily automated. Also, police laboratories could employ this
      method for rapid screening analysis to discourage adulteration practices.

PMID- 20685443
TI  - Electrochemical determination of some antidiabetic drugs for type 2 diabetic
      patients.
AB  - Quantitative determination of rosiglitazone, pioglitazone, glimepiride and
      glyburide as antidiabetic drugs for type 2 diabetic patients was performed
      conveniently and economically using cyclic voltammetry (CV) and differential
      pulse voltammetry (DPV). Carbon paste (CPE) and glassy carbon (GCE) electrodes
      were successfully used as sensors for these drugs in Briton-Robinson (B-R) as
      buffer solution. The preparation of CPE and the GCE as ion selective electrodes
      is based on the construction of 10% standard drug ion pair with reineckate or
      tungstophosphate imbedded as electroactive material. Working standards were
      freshly prepared just before the assay by dilution from a 10(-2)mol L(-1) drug
      stock solution. At a scan rate of 100 mV s(-1) the cyclic voltammograms showed a
      well defined anodic peak with high selectivity. The DVP gave a reproducible well
      defined diffusion controlled peak for each drug at a scan rate of 10 mV s(-1).
      The oxidation peaks were used to determine the tested drug concentrations. The
      quantitative determination of the four drugs in their pharmaceutical preparations
      by the proposed electrochemical technique was found to be identical with the
      values obtained by the standard HPLC method. A mean % recovery of 100+/-1 was
      obtained and the % relative standard deviation was 1.62 indicating the high
      precision of the method and the confidence in its repeatability. The proposed
      electroanalytical technique using either the CPE or the GCE is economic,
      selective and can be applied for both the qualitative and quantitative
      determination of the drugs in their pharmaceutical preparations, without special
      drug separation.

PMID- 20685444
TI  - AuAg bimetallic nanoparticles film fabricated based on H2O2-mediated silver
      reduction and its application.
AB  - A method to fabricate AuAg bimetallic nanoparticles film by H(2)O(2)-mediated
      reduction of silver was reported. Gold nanoparticles (Au NPs) were first adsorbed
      onto the surface of a self-assembled 2-aminoethanethiol monolayer-modified gold
      film or 3-aminopropyltriethoxysilane (APTES) monolayer-modified quartz slide.
      Upon further treatment of this modified film with the solution containing silver
      nitrate (AgNO(3)) and H(2)O(2), silver was deposited on the surface of Au NPs.
      The size of the AuAg bimetallic particles could be readily tuned by manipulating
      the concentration of H(2)O(2). Surface plasmon resonance (SPR) was used to
      investigate the process, the deposition of silver on Au NPs modified gold film
      resulted in an obvious decrease of depth in the SPR reflectance intensity and
      minimum angle curves (SPR R-theta curves), which may be utilized for the
      quantitative SPR detection of the analyte, H(2)O(2). Combination of the
      biocatalytic reaction that could yield H(2)O(2) by using the enzyme, glucose
      oxidase, with the deposition of silver may enable the design of a glucose
      biosensor by SPR technique. Furthermore, we evaluated the AuAg bimetallic
      nanoparticles film for their ability to be an effective substrate for surface
      enhanced Raman scattering (SERS).

PMID- 20685445
TI  - A new acetonitrile-free mobile phase method for LC-ELSD quantification of
      fructooligosaccharides in onion (Allium cepa L.).
AB  - Onion soluble non-structural carbohydrates consist of fructose, glucose and
      sucrose plus fructooligosaccharides (FOS) with degrees of polymerisation (DP) in
      the range of 3-19. In onion, sugars and FOS are typically separated using liquid
      chromatography (LC) with acetonitrile (ACN) as a mobile phase. In recent times,
      however, the production of ACN has diminished due, in part, to the current
      worldwide economic recession. A study was therefore undertaken, to find an
      alternative LC method to quantify sugars and FOS from onion without the need for
      ACN. Two mobile phases were compared; the first taken from a paper by Vagen and
      Slimestad (2008) using ACN mobile phase, the second, a newly reported method
      using ethanol (EtOH). The EtOH mobile phase eluted similar concentrations of all
      FOS compared to the ACN mobile phase. In addition, limit of detection, limit of
      quantification and relative standard deviation values were sufficiently and
      consistently lower for all FOS using the EtOH mobile phase. The drawback of the
      EtOH mobile phase was mainly the inability to separate all individual sugar
      peaks, yet FOS could be successfully separated. However, using the same onion
      extract, a previously established LC method based on an isocratic water mobile
      phase could be used in a second run to separate sugars. Although the ACN mobile
      phase method is more convenient, in the current economic climate a method based
      on inexpensive and plentiful ethanol is a valid alternative and could potentially
      be applied to other fresh produce types. In addition to the mobile phase solvent,
      the effect of extraction solvents on sugar and FOS concentration was also
      investigated. EtOH is still widely used to extract sugars from onion although
      previous literature has concluded that MeOH is a superior solvent. For this
      reason, an EtOH-based extraction method was compared with a MeOH-based method to
      extract both sugars and FOS. The MeOH-based extraction method was more
      efficacious at extracting sugars and FOS from onion flesh, eluting significantly
      higher concentrations of glucose, kestose, nystose and DP5-DP8.

PMID- 20685446
TI  - Characterization of emtricitabine related substances by liquid chromatography
      coupled to an ion trap mass spectrometer.
AB  - Emtricitabine (FTC) is an antiretroviral compound that inhibits the HIV-1 reverse
      transcriptase. For the quantification of FTC related substances, a liquid
      chromatography (LC) method coupled with ultraviolet (UV) detection was developed
      earlier in our laboratory. Several unknown compounds were detected during the
      analysis of a commercial sample. However, most of these impurities were not
      characterized. In this study, impurity profiling in a selected FTC sample was
      done using LC-mass spectrometry (MS). Due to the presence of a non-volatile
      buffer, a desalting procedure was carried out before sending the impurity into
      the MS. Totally, nine peaks were studied and most of them could be characterized.

PMID- 20685447
TI  - 1-Furoylthiourea-Sonogel-Carbon electrodes: structural and electrochemical
      characterization.
AB  - A new type of sensor based on Sonogel-Carbon materials modified with 1-(2-furoyl)
      3-(1-naphthyl)thiourea is presented to be used as an amperometric sensor for
      metals. Different percentages of modifier were tested in order to optimise the
      structural and mechanical properties, as well as the electrochemical behaviour.
      Scanning electron microscopy (SEM), X-ray energy dispersive spectroscopy (EDS),
      Fourier transform-infrared spectroscopy (FTIR), single crystal X-ray diffraction
      (XRD) and powder XRD were used for the structural characterization of these
      electrodes. The 1-(2-furoyl)-3-(1-naphthyl)thiourea did not modify significantly
      the structural and mechanical properties of the Sonogel-Carbon electrodes, being
      similar to other modifications carried out previously in these materials. For the
      study of the electrochemical response, anodic stripping differential pulse
      voltammetry (ASDPV) was employed, optimising other parameters of measurement such
      as pH of the buffer, potential and accumulation time and pulse amplitude. The
      electrochemical response of the modified electrodes improved significantly with
      respect to the non-modified electrode, giving good signals and acceptable
      detection limit.

PMID- 20685448
TI  - Multisyringe chromatography (MSC) using a monolithic column for the determination
      of sulphonated azo dyes.
AB  - A methodology based on multisyringe chromatography with a monolithic column was
      developed to determine three sulphonated azo textile dyes: Acid Yellow 23, Acid
      Yellow 9 and Acid Red 97. An ion pair reagent was needed because of the low
      affinity between the monolithic column and the anionic dyes. The proposed
      analytical system is simple, versatile and low-cost and has great flexibility in
      manifold configuration. The method was optimized through experimentation based on
      experimental design methodology. For this purpose two blocks of full factorial
      2(3) were done sequentially. In the first experimental plan, the factors studied
      were: the % of acetonitrile in organic phase, the % of H(2)O in the mobile phase
      and the kind of ion pair reagent. In this stage, a simple configuration was used
      which has only one syringe for the mobile phase. After the first experimentation,
      we added a second syringe with a second mobile phase to the multisyringe module
      and performed a second full factorial 2(3). The factors studied in this case
      were: the % of acetonitrile in the second mobile phase, the pH and the
      concentration of ion pair reagent in both mobile phases. After this design, the
      optimal conditions were selected for obtaining a good resolution between the
      peaks of yellow dyes (1.47) and the elution of red dye in less than 8 min. The
      methodology was validated by spiking different amounts of each dye in real water
      samples, specifically, tap water, well water and water from a biological
      wastewater lagoon.

PMID- 20685449
TI  - Characterisation of commercially available linear alkylbenzenesulfonates by LC
      SPE-NMR/MS (liquid chromatography-solid phase extraction-nuclear magnetic
      resonance spectroscopy-mass spectroscopy).
AB  - Commercially available linear alkylbenzenesulfonates (LASs) are a mixture of
      various homologues and isomers, leading to 20 major species. In this work we
      investigated the commercial product by liquid chromatography-solid phase
      extraction-nuclear magnetic resonance spectroscopy-mass spectrometry (LC-SPE
      NMR/MS). The commercial product was separated into 17 fractions by liquid
      chromatography (LC). After chromatographic separation, 5% of the flow was split
      to a mass spectrometer (MS) while 95% was send to post-column solid phase
      extraction cartridges for enrichment of the analytes (LC-SPE). After elution from
      the SPE-cartridges a NMR-spectrometer equipped with a cryo-probe was used for the
      characterisation of the different LASs species. For the first time (1)H-1D and H
      H-COSY spectra for 14 LASs species out of 20 major isomers are presented, whereas
      the 6 remaining species are detected as mixtures in 3 (1)H-1D and H-H-COSY
      spectra. These data were used to correlate the chromatographic retention of the
      LASs isomers to the substitution pattern of the alkyl chain.

PMID- 20685450
TI  - Experimental study on stability of different solid contact arrangements of ion
      selective electrodes.
AB  - Comparison of potentials stability of different types of solid contact lead
      selective electrodes is presented. Conducting polymer based sensors (hydrophilic
      and conducting - poly(3,4-ethylenedioxythiophene) or hydrophobic and
      semiconducting-polyoctylthiophene) were studied in parallel with coated wire and
      hydrogel (poly(hydroxyethylmethacrylate)) contact electrodes. The within day and
      between days potential stability was compared, highlighting the effect of sensor
      storing conditions. The obtained results clearly demonstrate that different
      conclusions on stability of sensors' potential can be drawn depending on
      experimental protocol applied. Polyoctylthiophene based contacts show superior
      within day stability with no influence of dry storage. On the other hand, a
      chronopotentiometric method of stability evaluation clearly prefers poly(3,4
      ethylenedioxythiophene) based sensors, pointing to smallest resistance and
      polarizability. It is clearly shown that the choice of experimental conditions
      applied to test stability can favor particular type of contact used. The
      inductively coupled plasma mass spectrometry with laser ablation (LA-ICP-MS)
      experiments conducted for different arrangements tested has shown that for
      poly(3,4-ethylenedioxythiophene) and poly(hydroxyethylmethacrylate) type contacts
      longer contact time with lead(II) solution results in changes in the elemental
      composition of the transducer layer. On the other hand, in line with high
      stability observed under potentiometric conditions, no changes were seen for
      polyoctylthiophene based transducer.

PMID- 20685451
TI  - Overcoming matrix interferences in ion-exchange solid phase extraction of As, Cr,
      Mo, Sb, Se and V species from leachates of cement-based materials using multiple
      extractions.
AB  - Solid phase extraction (SPE) methods based on multiple extractions have been
      developed to overcome matrix interferences in the charge-based fractionation
      analysis of As, Cr, Mo, Sb, Se and V leached from cement-based materials.
      Disposable SPE tubes packed with 500 mg strong anion-exchange (SAX) or strong
      cation-exchange (SCX) sorbents were used to extract the anionic and cationic
      species of the elements, respectively. The multiple extractions were based on the
      percolation of a small sample volume (5.0 mL) through a series of identical ion
      exchange tubes. For most of the elements, more than 90% of the anionic species
      were extracted from a sample containing up to 16 g L(-1) NO(3)(-) by passing the
      aliquot through five identical SAX tubes. Percolating a sample aliquot through
      three identical SCX cartridges gave more than 99% retention for Cr(III) from
      leachates containing a high concentration of interfering metal cations. The
      anionic and cationic analytes showed only slight non-specific adsorption on the
      SCX and SAX sorbents, respectively, except for V(V) on the SCX sorbent. A
      condition was established for the quantitative elution of the retained analytes
      from the ion-exchange sorbents with 1.0 mol L(-1) HNO(3). The multiple ion
      exchange SPE procedures were validated using spike recovery tests. The methods
      were used to determine the anionic and cationic fractions of the target elements
      in concrete leachates covering a broad range of pH (3.8-13.4). The elements were
      found to exist predominantly as anions in the alkaline and neutral leachates. A
      high fraction (85%) of cationic Cr was detected in the most acidic leachate (pH
      3.8).

PMID- 20685452
TI  - Determination of thiodicarb using a biosensor based on alfalfa sprout peroxidase
      immobilized in self-assembled monolayers.
AB  - A biosensor based on alfalfa sprout (Medicago sativa) homogenate as a source of
      peroxidase is proposed for the determination of thiodicarb by square-wave
      voltammetry. This enzyme was immobilized in self-assembled monolayers of l
      cysteine on a gold electrode. Several parameters were investigated to evaluate
      the optimum conditions for operation of the biosensor. The analytical curve was
      linear for thiodicarb concentrations of 2.27 x 10(-6) to 4.40 x 10(-5) mol L(-1)
      with a detection limit of 5.75 x 10(-7) mol L(-1). The lifetime of the Au-alfalfa
      sprout-SAMs was 20 days (at least 220 determinations). The average recovery of
      thiodicarb from samples of vegetable extracts ranged from 99.02 to 101.04%. The
      results obtained for thiodicarb in vegetable extracts using the proposed method
      are in close agreement with those using a high performance liquid chromatography
      procedure at the 95% confidence level.

PMID- 20685453
TI  - Determination of ochratoxin A and T-2 toxin in alcoholic beverages by hollow
      fiber liquid phase microextraction and ultra high-pressure liquid chromatography
      coupled to tandem mass spectrometry.
AB  - A new method for the determination of ochratoxin A and T-2 toxin in alcoholic
      beverages (wine and beer) by hollow fiber liquid microextraction was optimized.
      The extraction step was followed by ultra high-pressure liquid chromatography
      coupled to tandem mass spectrometry (UHPLC-MS/MS). The extraction procedure was
      based on the extraction of mycotoxins from the sample to the organic solvent (1
      octanol) immobilized in the fiber, and afterwards, they were desorbed in a
      mixture of acetonitrile/water (80:20, v/v) at pH 7 prior to chromatographic
      determination. Different variables affecting the extraction process such as
      organic solvent, salt content, extraction time and desorption solution were
      studied. The developed method was validated in wine and beer, using white wine
      and alcoholic beer as representative matrices for both types of samples. Relative
      recoveries higher than 70% were obtained for the selected mycotoxins. Good
      linearity (R(2)>0.993) was obtained and quantification limits (0.02-0.09 microg
      L(-1)) below European regulatory levels were achieved. Repeatability, expressed
      as relative standard deviation, was always lower than 12%, whereas interday
      precision was lower than 21%. The proposed method was applied to the analysis of
      several types of wines and beers and ochratoxin A was detected in a rose wine at
      1.1 microg L(-1).

PMID- 20685454
TI  - Preparation of gold nanoparticles on eggshell membrane and their biosensing
      application.
AB  - A facile green biosynthesis method has been successfully developed to prepare
      gold nanoparticles (AuNPs) of various core sizes (25+/-7 nm) using a natural
      biomaterial, eggshell membrane (ESM) at ambient conditions. In situ synthesis of
      AuNPs-immobilized ESM is conducted in a simple manner by immersing ESM in a pH
      6.0 aqueous solution of HAuCl(4) without adding any reductant. The formation of
      AuNPs on ESM protein fibers is attributed to the reduction of Au(III) ions to
      Au(0) by the aldehyde moieties of the natural ESM fibers. Energy dispersive X-ray
      spectroscopy, scanning electron microscopy, X-ray photoelectron spectroscopy, and
      X-ray powder diffraction unambiguously identify the presence of AuNPs on ESM. The
      effect of pH on the in situ synthesis of AuNPs on ESM has been investigated in
      detail. The pH of the gold precursor (HAuCl(4)) solution can influence the
      formation rate, dispersion and size of AuNPs on ESM. At pH < or =3.0 and > or
      =7.0, no AuNPs are observed on ESM while small AuNPs are homogeneously dispersed
      on ESM at pH 4.0-6.0. The optimal pH for AuNPs formation on ESM is 6.0.
      AuNPs/ESMs are used to immobilize glucose oxidase (GO(x)) for glucose biosensing.
      AuNPs on ESM can increase the enzyme activity of GO(x). The linear response range
      of the glucose biosensor is 20 microM to 0.80 mM glucose with a detection limit
      of 17 microM (S/N=3). The biosensor has been successfully applied to determine
      the glucose content in commercial glucose injections. Our work provides a very
      simple, non-toxic, convenient, and green route to synthesize AuNPs on ESM which
      is potentially useful in the biosensing field.

PMID- 20685455
TI  - Development and application of a validated stability-indicating HPLC method for
      simultaneous determination of granisetron hydrochloride, benzyl alcohol and their
      main degradation products in parenteral dosage forms.
AB  - A simple, rapid and sensitive reversed phase high performance liquid
      chromatographic method using photodiode array detection was developed and
      validated for the simultaneous determination of granisetron hydrochloride, benzyl
      alcohol, 1-methyl-1H-indazole-3-carboxylic acid (the main degradation product of
      granisetron) and benzaldehyde (the main degradation product of benzyl alcohol) in
      granisetron injections. The separation was achieved on Hypersil BDS C8 (250 mm x
      4.6 mm i.d., 5 microm particle diameter) column using a mobile phase consisted of
      acetonitrile:0.05 M KH(2)PO(4):triethylamine (22:100:0.15) adjusted to pH 4.8.
      The column was maintained at 25 degrees C and 20 microL of solutions was
      injected. Photodiode array detector was used to test the peak purity and the
      chromatograms were extracted at 210 nm. Naphazoline hydrochloride was used as
      internal standard. The method was validated with respect to specificity,
      linearity, accuracy, precision, limit of quantitation and limit of detection. The
      validation acceptance criteria were met in all cases. Identification of the pure
      peaks was carried out using library match programmer and wavelengths of
      derivative optima of the spectrograms of the peaks. The method was successfully
      applied to the determination of the investigated drugs and their degradation
      products in different batches of granisetron injections. The method was proved to
      be sensitive for the determination down to 0.03 and 0.01% of granisetron
      degradation product and benzaldehyde, respectively, which are far below the
      compendia limits for testing these degradation products in their corresponding
      intact drugs.

PMID- 20685456
TI  - Direct electrocatalytic oxidation of nitric oxide and reduction of hydrogen
      peroxide based on alpha-Fe2O3 nanoparticles-chitosan composite.
AB  - alpha-Fe(2)O(3) nanoparticles prepared using a simple solution-combusting method
      have been dispersed in chitosan (CH) solution to fabricate nanocomposite film on
      glass carbon electrode (GCE). The as-prepared alpha-Fe(2)O(3) nanoparticles were
      characterized by powder X-ray diffraction (XRD), scanning electron microscopy
      (SEM). The nanocomposite film exhibits high electrocatalytic oxidation for nitric
      oxide (NO) and reduction for hydrogen peroxide (H(2)O(2)). The electrocatalytic
      oxidation peak is observed at +0.82 V (vs. Ag/AgCl) and controlled by diffusion
      process. The electrocatalytic reduction peak is observed at -0.45 V (vs. Ag/AgCl)
      and controlled by diffusion process. This alpha-Fe(2)O(3)-CH/GCE nanocomposite
      bioelectrode has response time of 5 s, linearity as 5.0 x 10(-7) to 15.0 x 10(-6)
      M of NO with a detection limit of 8.0 x 10(-8) M and a sensitivity of -283.6
      microA/mM. This alpha-Fe(2)O(3)-CH/GCE nanocomposite bioelectrode was further
      utilized in detection of H(2)O(2) with a detection limit of 4.0 x 10(-7) M,
      linearity as 1.0 x 10(-6) to 44.0 x 10(-6) M and with a sensitivity of 21.62
      microA/mM. The shelf life of this bioelectrode is about 6 weeks under room
      temperature conditions.

PMID- 20685457
TI  - Reverse flow injection spectrophotometric for determination of aluminium(III).
AB  - A reverse flow injection analysis (rFIA) spectrophotometric method has been
      developed for the determination of aluminium(III). The method was based on the
      reaction of Al(III), quercetin and cetyltrimethylammonium bromide (CTAB),
      yielding a yellow colored complex in an acetate buffer medium (pH 5.5) with
      absorption maximum at 428 nm. The rFIA parameters that influence the FIA peak
      height have been optimized in order to obtain the best sensitivity and minimum
      reagent consumption. A linear relationship between the relative peak height and
      Al(III) concentrations were obtained over the concentration range of 0.02-0.50 mg
      L(-1) with a correlation coefficient of 0.9998. The limit of detection (LOD,
      defined as 3sigma) and limit of quantification (LOQ, defined as 10sigma) were
      0.007 and 0.024 mg L(-1), respectively. The repeatability was 1.10% (n=11) for
      0.2 mg L(-1) Al(III). The proposed method was applied to the determination of
      Al(III) in tap water samples with a sampling rate of 60 h(-1). Results obtained
      were in good agreement with those obtained by the official ICP-MS method at the
      95% confidence level.

PMID- 20685458
TI  - Separation/preconcentration and determination of vanadium with dispersive liquid
      liquid microextraction based on solidification of floating organic drop (DLLME
      SFO) and electrothermal atomic absorption spectrometry.
AB  - A novel dispersive liquid-liquid microextraction based on solidification of
      floating organic drop (DLLME-SFO) for separation/preconcentration of ultra trace
      amount of vanadium and its determination with the electrothermal atomic
      absorption spectrometry (ETAAS) was developed. The DLLME-SFO behavior of vanadium
      (V) using N-benzoyl-N-phenylhydroxylamine (BPHA) as complexing agent was
      systematically investigated. The factors influencing the complex formation and
      extraction by DLLME-SFO method were optimized. Under the optimized conditions:
      100 microL, 200 microL and 25 mL of extraction solvent (1-undecanol), disperser
      solvent (acetone) and sample volume, respectively, an enrichment factor of 184, a
      detection limit (based on 3S(b)/m) of 7 ng L(-1) and a relative standard
      deviation of 4.6% (at 500 ng L(-1)) were obtained. The calibration graph using
      the preconcentration system for vanadium was linear from 20 to 1000 ng L(-1) with
      a correlation coefficient of 0.9996. The method was successfully applied for the
      determination of vanadium in water and parsley.

PMID- 20685459
TI  - Development of a novel strategy for preconcentration of antibiotic residues in
      milk and their quantitation by capillary electrophoresis.
AB  - A novel analytical method based on capillary zone electrophoresis coupled with
      diode array detection is developed and validated for the identification and
      simultaneous quantitation of four antibiotics in bovine raw milk. The studied
      antibiotics belong to different groups: beta-lactams, tetracyclines, quinolones,
      amphenicols and sulfonamides. An experimental design including both a factorial
      and a central composite design allowed a reduction in the number of optimization
      experiments. The multiple response criterion was successfully used to optimize
      the separation between chloramphenicol, ciprofloxacin, ampicillin, tetracycline
      and sulfamethoxazol, allowing the reduction of the analysis time with excellent
      peak resolutions and low capillary current. Different strategies for
      preconcentration and extraction of the studied antibiotics were applied, in order
      to remove potential interferences from the sample and to increase the
      sensitivity. Milk samples were prepared by a clean-up/extraction procedure based
      on protein precipitation with trichloroacetic acid followed by liquid-liquid
      extraction with dichloromethane combined with solid-phase extraction, and
      injection into the electrophoretic system hydrodynamically. The limits of
      detection and quantification (below 30 and 100 microg L(-1), respectively) were
      in all cases lower than the maximum residue limits tolerated for these compounds
      in milk. Accuracy was evaluated by computing recoveries for the target
      antibiotics which were between 93.08% and 102.89%.

PMID- 20685460
TI  - Successive projections algorithm applied to spectral data for the simultaneous
      determination of flavour enhancers.
AB  - A novel variable selection strategy for multiple lineal regression (MLR), the
      successive projections algorithm (SPA), was applied to spectrophotometric data
      (190-320 nm) for the simultaneous determination of monosodium glutamate (MSG),
      guanosine-5'-monophosphate (GMP) and inosine-5'-monophosphate (IMP) in dehydrated
      broths samples. This selection method uses simple operations in a vector space to
      minimize variable collinearity and has become an interesting variable selection
      strategy for multivariate calibration. In this work, nine, six and four
      wavelengths for MSG, GMP and IMP, respectively, were selected to construct
      calibrations models in order to solve successfully the serious spectral
      overlapping in samples containing these analytes. The relative errors of
      prediction (REP) for the validation set were 2.3%, 0.9% and 1.8% for MSG, GMP and
      IMP, respectively. Commercial samples were analysed and a recovery study was
      carried out to verify the accuracy of the proposed method with satisfactory
      results. A continuous flow system was used to develop a simple, cheap and rapid
      method (sample throughput: 200 h(-1)), without any previous extraction step.

PMID- 20685461
TI  - Comparison of hot Soxhlet and accelerated solvent extractions with microwave and
      supercritical fluid extractions for the determination of polycyclic aromatic
      hydrocarbons and nitrated derivatives strongly adsorbed on soot collected inside
      a diesel particulate filter.
AB  - Several methods of extraction were optimized to extract polycyclic aromatic
      hydrocarbons (PAHs), their nitrated derivatives and heavy n-alkanes from a highly
      adsorptive particulate matter resulting from the combustion of diesel fuel in a
      diesel engine. This particular carbonaceous particulate matter, collected at high
      temperatures in cordierite diesel particulate filters (DPF), which are optimized
      for removing diesel particles from diesel engine exhaust emissions, appeared
      extremely refractory to extractions using the classical extracting conditions for
      these pollutants. In particular, the method of accelerated solvent extraction
      (ASE) is described in detail here. Optimization was performed through
      experimental design to understand the impact of each factor studied and the
      factors' possible interactions on the recovery yields. The conventional
      extraction technique, i.e., Soxhlet extraction, was also carried out, but the
      lack of quantitative extractions led us to use a more effective approach: hot
      Soxhlet. It appeared that the extraction of the heaviest PAHs and nitroPAHs by
      either the optimized ASE or hot Soxhlet processes was far from complete. To
      enhance recovery yields, we tested original solvent mixtures of aromatic and
      heteroaromatic solvents. Thereafter, these two extraction techniques were
      compared to microwave-assisted extraction (MAE) and supercritical fluid
      extraction (SFE). In every case, the only solvent mixture that permitted
      quantitative extraction of the heaviest PAHs from the diesel soot was composed of
      pyridine and diethylamine, which has a strong electron-donor character.
      Conversely, the extraction of the nitrated PAHs was significantly improved by the
      use of an electron-acceptor solvent or by introducing a small amount of acetic
      acid into the pyridine. It was demonstrated that, for many desirable features, no
      single extraction technique stound out as the best: ASE, MAE or SFE could all
      challenge hot Soxhlet for favourable extractions. Consequently, the four
      optimized extraction techniques were performed to extract the naturally polluted
      diesel soot collected inside the DPF. Comparisons with the NIST standard
      reference material SRM 1650b showed that the soot collected from the DPF
      contained 50% fewer n-alkanes, and also markedly lower levels of PAHs (44 less
      concentrated) than SRM 1650b, and that the ratio of nitroPAHs to PAHs was
      increased. These results were attributed to the high temperatures reached inside
      the particulate filter during sampling runs and to the contribution of the
      catalytic DPF to aromatic and aliphatic hydrocarbons abatement.

PMID- 20685462
TI  - Simple methods for characterization of metals in historical textile threads.
AB  - Characterization of metal threads on historical textile materials is important
      for preservation of valuable cultural heritage. Obtained results dictate
      decisions on cleaning, conservation and restoration steps. The most important
      part of characterization is chemical analysis of originally applied materials,
      since this enables understanding the nature of chemical and physical degradation
      and determines the cleaning methods. Methods applied should be non-destructive
      and sensitive enough to detect trace elements in small sample amounts. The goal
      of this research was to describe the most useful procedures for fast and simple
      determination of specific metals of interest. Therefore we propose application of
      scanning electron microscopy equipped with EDS detector (SEM-EDS) for sample
      surface analysis and inductively coupled plasma-optical emission spectroscopy
      (ICP-OES) for chemical analysis of metals threads. For quality insurance reasons,
      a comparative method applied for chemical analysis was atomic absorption
      spectrometry (AAS). This combination of methods has proven to be very useful in
      analysis of historical samples, since SEM-EDS was a simple and non-destructive
      method which provided information on chemical composition of sample surfaces,
      while ICP-OES and AAS enabled the full insight into the average chemical
      composition of samples. Nevertheless, both ICP-OES and AAS were destructive
      methods which demanded dissolving of samples prior to the analysis. In this work
      nine different metal fibers collected from historical textile materials were
      characterized. Proposed methods enabled obtaining information on sample
      constitution, morphology, topology and chemical composition.

PMID- 20685463
TI  - Comparison of three methods for fractionation and enrichment of low molecular
      weight proteins for SELDI-TOF-MS differential analysis.
AB  - In most diseases, the clinical need for serum/plasma markers has never been so
      crucial, not only for diagnosis, but also for the selection of the most efficient
      therapies, as well as exclusion of ineffective or toxic treatment. Due to the
      high sample complexity, prefractionation is essential for exploring the deep
      proteome and finding specific markers. In this study, three different sample
      preparation methods (i.e., highly abundant protein precipitation, restricted
      access materials (RAM) combined with IMAC chromatography and peptide ligand
      affinity beads) were investigated in order to select the best fractionation step
      for further differential proteomic experiments focusing on the LMW proteome (MW
      inferior to 40,000 Da). Indeed, the aim was not to cover the entire plasma/serum
      proteome, but to enrich potentially interesting tissue leakage proteins. These
      three methods were evaluated on their reproducibility, on the SELDI-TOF-MS
      peptide/protein peaks generated after fractionation and on the information
      supplied. The studied methods appeared to give complementary information and
      presented good reproducibility (below 20%). Peptide ligand affinity beads were
      found to provide efficient depletion of HMW proteins and peak enrichment in
      protein/peptide profiles.

PMID- 20685464
TI  - Application of selected ion monitoring to the analysis of triacylglycerols in
      olive oil by high temperature-gas chromatography/mass spectrometry.
AB  - The analysis of the triacylglycerol (TAG) composition of oils is a very
      challenging task, since the TAGs have very similar physico-chemical properties.
      In this work, a high temperature-gas chromatographic method coupled to electron
      ionization-mass spectrometry (HT-GC/EI-MS), in the Selected Ion Monitoring (SIM)
      mode, method was developed for the analysis of TAGs in the olive oil; this is a
      method suitable for routine analysis. This method was developed using
      commercially available standard TAGs. The TAGs studied were separated according
      to their equivalent carbon number and degree of unsaturation. The peak assignment
      was carried out by locating the characteristic fragment ions having the same
      retention time on the SIM profile such as [RCO+74](+) and [RCO+128](+) ions, due
      to the fatty acyl residues on sn-1, sn-2 and sn-3 positions of the TAG molecule
      and the [M-OCOR](+) ions corresponding to the acyl ions. The developed method was
      very useful to eliminate the interferences that appeared in the mass spectrum
      since electron ionization can prevent satisfactory interpretation of spectra.

PMID- 20685465
TI  - Fast throughput, highly sensitive determination of allergenic disperse dyes in
      textile products by use of sample composition.
AB  - A simple, highly sensitive and fast procedure for the control of allergenic
      disperse dyes in textile products was optimized. The method is based on
      ultrasound assisted extraction of textile samples with 20 mL of methanol under
      controlled conditions (15 min, 70 degrees C) followed by separation and analysis
      by LC-MS-MS. The sample preparation process was optimized by means of a surface
      response experimental design and provided quantitative recoveries of dyes, much
      better than the poor recoveries provided by current standard procedures. The
      chromatographic separation was optimized by means of computer-assisted method
      development by use of a special chemometric tool developed specifically for LC-MS
      systems, as previously reported by the authors. The result is a rapid
      chromatographic procedure that enables accurate quantification, at very low
      concentrations, of all 23 allergenic and/or carcinogenic disperse dyes
      considered. Matrix effects in the LC-MS procedure were studied. Under the
      experimental conditions, both conventional and strategic sample composition are
      proposed as efficient procedures that reduce the costs and work involved in the
      control of allergenic dyes in finished textile products. The benefits of
      strategic sample composition are demonstrated by means of an example case study,
      and the pros and cons of preparing the composite samples from sample extracts or
      directly from textile products are discussed.

PMID- 20685466
TI  - On-line coupling of in-tube boronate affinity solid phase microextraction with
      high performance liquid chromatography-electrospray ionization tandem mass
      spectrometry for the determination of cis-diol biomolecules.
AB  - Boronate affinity solid phase microextraction (BA-SPME) is a new format appeared
      recently with great potential for specific extraction of cis-diol-containing
      compounds. Unlike conventional SPME, BA-SPME relies on covalent interactions and
      thereby features with specific selectivity, eliminated matrix effect and
      manipulable capture/release. However, only on-fiber BA-SPME and its off-line
      combination with high performance liquid chromatography (HPLC) have been reported
      so far. In this study, we report on-line coupling of in-tube BA-SPME with HPLC
      electrospray ionization tandem mass spectroscopy (in-tube BA-SPME-HPLC-ESI-MS/MS)
      for the specific and sensitive determination of cis-diol-containing biomolecules.
      A boronate affinity extraction phase was prepared onto the inner surface of the
      capillary by copolymerization of vinylphenylboronic acid (VPBA) and ethylene
      glycol dimethacrylate (EDMA). The extraction conditions were optimized by
      choosing appropriate extraction/desorption solutions and extraction time. The
      extraction capacity, linear range, reproducibility and life-time were
      investigated. The developed method was successfully applied for the determination
      of dopamine in urine samples. Since many cis-diol-containing compounds are of
      great biological importance, the in-tube BA-SPME-HPLC method can be a promising
      tool.

PMID- 20685467
TI  - Development of a sensitive detection method of cancer biomarkers in human serum
      (75%) using a quartz crystal microbalance sensor and nanoparticles amplification
      system.
AB  - A simple and sensitive sensor method for cancer biomarkers [prostate specific
      antigen (PSA) and PSA-alpha 1-antichymotrypsin (ACT) complex] analysis was
      developed, to be applied directly with human serum (75%) by using antibody
      modified quartz crystal microbalance sensor and nanoparticles amplification
      system. A QCM sensor chip consisting of two sensing array enabling the
      measurement of an active and control binding events simultaneously on the sensor
      surface was used in this work. The performance of the assay and the sensor was
      first optimised and characterised in pure buffer conditions before applying to
      serum samples. Extensive interference to the QCM signal was observed upon the
      analysis of serum. Different buffer systems were then formulated and tested for
      the reduction of the non-specific binding of sera proteins on the sensor surface.
      A PBS buffer containing 200 microg mL(-1) BSA, 0.5 M NaCl, 500 microg mL(-1)
      dextran and 0.5% Tween 20, was then selected which eliminated the interfering
      signal by 98% and enabled the biomarker detection assay to be performed in 75%
      human serum. By using Au nanoparticles to enhance the QCM sensor signal, a limit
      of detection of 0.29 ng mL(-1) PSA and PSA-ACT complex (in 75% serum) with a
      linear dynamic detection range up to 150 ng mL(-1) was obtained. With the
      achieved detection limit in serum samples, the developed QCM assay shows a
      promising technology for cancer biomarker analysis in patient samples.

PMID- 20685468
TI  - Determination of esters in glycerol phase after transesterification of vegetable
      oil.
AB  - In biodiesel production, glycerol is formed as a side product and it is contained
      in the glycerol phase. This phase contains (besides glycerol): water, soaps,
      alcohol, traces of catalyst and glycerides and the remaining esters. In this
      paper, a new method for the determination of esters in the glycerol phase is
      introduced. The determination enables the minimization of the losses of biodiesel
      within the production process. It is based on the gradient RP-LC method (water
      and acetonitrile) with refractometric detection. The analysis is easy and the
      samples do not need any treatment (only dilution by water) and has a low
      detection limit. The results of this method were compared with the results of two
      other published methods: isocratic HPLC and GC. The disadvantage of these two
      methods is that they need extensive treatment of the sample, which takes many
      hours, and they are able to determine only the sum of esters. The new method is
      reliable, much faster and able to differentiate esters of almost each higher
      fatty acid (e.g. linoleic, linolenic, strearic alkyl ester) in the glycerol
      phase.

PMID- 20685469
TI  - Electroanalytical characteristics of antipsychotic drug ziprasidone and its
      determination in pharmaceuticals and serum samples on solid electrodes.
AB  - Ziprasidone is a psychotropic agent used for the treatment of schizophrenia. Its
      oxidation was investigated electrochemically at boron-doped diamond and glassy
      carbon electrodes using cyclic, differential pulse, and square wave voltammetry.
      The dependence of the peak current and peak potentials on pH, concentration,
      nature of the buffer, and scan rate were examined. The process was diffusion and
      adsorption controlled for boron-doped diamond and glassy carbon electrodes,
      respectively. The possible mechanism of oxidation was discussed with some model
      compounds that have indole and piperazine oxidations. A linear response was
      obtained between 8 x 10(-7) and 8 x 10(-5) M for the first peak in acetate buffer
      (pH 5.5) and between 2 x 10(-6) and 2 x 10(-4) M for the second peak in 0.1 M
      H(2)SO(4) with boron-doped diamond electrode for differential pulse and square
      wave voltammetric techniques. The reproducibility and accuracy of the proposed
      methods were found between 0.31 and 1.20, 99.27 and 100.22, respectively. The
      recovery studies were also achieved to check selectivity and accuracy of the
      methods. The proposed methods were applied for the determination of ziprasidone
      from pharmaceutical dosage forms and human serum samples without any time
      consuming extraction, separation, evaporation or adsorption steps prior to drug
      assay except precipitation of the proteins using acetonitrile. The results were
      statistically compared with those obtained through an established LC-UV
      technique, no significant differences were been found between the voltammetric
      and LC methods.

PMID- 20685470
TI  - Solid-phase microextraction followed by gas chromatography-mass spectrometry for
      the determination of ink photo-initiators in packed milk.
AB  - A novel, single step method for the determination of seven ink photo-initiators
      in carton packed milk samples is described. Solid-phase microextraction (SPME)
      and gas chromatography (GC), combined with mass spectrometry (MS), were used as
      sample preparation and determination techniques, respectively. Parameters
      affecting the performance of the microextraction process were thoroughly
      evaluated using uni- and multivariate optimization strategies, based on the use
      of experimental factorial designs. The coating of the SPME fibre, together with
      the sampling mode and the temperature were the factors playing a major influence
      on the efficiency of the extraction. Under final conditions, 1.5 mL of milk and
      8.5 mL of ultrapure water were poured in a glass vessel, which was closed and
      immersed in a water boiling bath. A poly(dimethylsiloxane)-divinylbenzene (PDMS
      DVB) coated fibre was exposed directly to the diluted sample for 40 min. After
      that, the fibre was desorbed in the injector of the GC-MS system for 3 min. The
      optimized method provided limits of quantification (LOQs) between 0.2 and 1
      microg L(-1) and a good linearity in the range between 1 and 250 microg L(-1).
      The inter-day precision remained below 15% for all compounds in spiked whole
      milk. The efficiency of the extraction changed for whole, semi-skimmed and
      skimmed milk; however, no differences were noticed among the relative recoveries
      achieved for milk samples, from different brands, with the same fat content.

PMID- 20685471
TI  - Novel surface molecularly imprinted material modified multi-walled carbon
      nanotubes as solid-phase extraction sorbent for selective extraction gallium ion
      from fly ash.
AB  - A new gallium (Ga(III)) ion-imprinted multi-walled carbon nanotubes (CNTs)
      composite sorbent was synthesized by a surface imprinting technique. The Ga(III)
      ion-imprinted/multi-walled carbon nanotubes (Ga(III)-imprinted/CNTs) sorbent was
      characterized by Fourier transform infrared (FT-IR), X-ray diffraction (XRD),
      nitrogen adsorption experiment, static adsorption experiment, and solid-phase
      extraction (SPE) experiment. The effects of sample volume, sample pH, washing and
      elution conditions on the extraction of Ga(III) ion from real sample were studied
      in detail. The imprinted sorbent offered a fast kinetics for the adsorption of
      Ga(III). The maximum static adsorption capacity of the imprinted sorbent towards
      was 58.8 micromol g(-1). The largest selectivity coefficient for Ga(III) in the
      presence of Al(III) was over 57.3. Compared with non-imprinted sorbent, the
      imprinted sorbent showed good imprinting effect for Ga(III) ion, the imprinting
      factor (alpha) was 2.6, the selectivity factor (beta) was 2.4 and 2.9 for Al(III)
      and Zn(II), respectively. The developed imprinted SPE method was applied
      successfully to the detection of trace Ga(III) ion in fly ash samples with
      satisfactory results.

PMID- 20685472
TI  - A coumarin based ICT probe for fluoride in aqueous medium with its real
      application.
AB  - A new coumarin based hydrazone (receptor 1) synthesized by modifying one of our
      earlier reported receptor detected fluoride ion selectively through naked eye in
      aq. DMSO (5:95, v/v). It was also able to detect fluoride through naked eye in a
      toothpaste sample. The addition of 1 equiv. of fluoride as its tetrabutylammonium
      salt to the 5 x 10(-5) M aq. DMSO solution of the receptor 1 produced red color
      while the similar addition of acetate produced faint pink color. The
      dihydrogenphosphate and a variety of other anions were not able to produce any
      significant color change with receptor 1 under similar experimental conditions.
      The corresponding UV-vis measurements showed a bathochromic shifting of 455 nm
      band of receptor 1 to 514 and 484 nm for fluoride and acetate, respectively. The
      non-linear fittings of corresponding UV-vis titration data in 1:1 binding
      equation yielded association constants in 10(5):1 ratio for fluoride and acetate,
      respectively. The (1)H NMR titrations studies shade further light on their mode
      of binding with receptor 1. The quantum mechanical calculations through time
      dependant density functional theory (TD-DFT) using basis set b3lyp/6-311g**
      supported our experimental findings nicely.

PMID- 20685473
TI  - Application of a novel co-enzyme reactor in chemiluminescence flow-through
      biosensor for determination of lactose.
AB  - A novel enzyme reactor with co-immobilization of beta-galactosidase and glucose
      oxidase in calcium alginate fiber (CAF) and amine modified nanosized mesoporous
      silica (AMNMS) was prepared which incorporate the adsorption and catalysis of
      AMNMS with the cage effect of the polymer to increase catalytic activity and
      stability of immobilized enzyme. The enzyme reactor was applied to prepare a
      chemiluminescence (CL) flow-through biosensor for determination of lactose
      combined with a novel luminol-diperiodatonickelate (DPN) CL system we reported.
      It shows that the CL flow-through biosensor possesses long lifetime, high
      stability, high catalytic activity and sensitivity. The relative CL intensity was
      linear with the lactose concentration in the range of 8 x 10(-8) - 4 x 10(-6) g
      mL(-1) with the detection limit of 2.7 x 10(-8) g mL(-1) (3sigma). It has been
      successfully applied to the determination of lactose in milk.

PMID- 20685474
TI  - Spectrofluorimetry in organized media coupled to second-order multivariate
      calibration for the determination of galantamine in the presence of uncalibrated
      interferences.
AB  - The present article describes the spectrofluorimetric determination of
      galantamine, a widely used acetylcholinesterase inhibitor, through excitation
      emission fluorescence matrices and second-order calibration. With the purpose of
      enhancing the fluorescence intensity of this substance, the effect of different
      organized assemblies was evaluated. Although the interaction of galantamine with
      different cyclodextrins is weak, it was corroborated that the fluorescence
      intensity of this pharmaceutical in the presence of alpha-cyclodextrin is
      increased by a twofold factor. Among the studied micellar media, the anionic
      surfactant sodium dodecyl sulfate produced the largest signals for the compound
      of interest (sixfold enhancement), and was selected as auxiliary reagent for the
      subsequent determinations. The developed approach enabled the determination of
      galantamine at the ng mL(-1) level without the necessity of applying separation
      steps, and in the presence of uncalibrated interferences. The applied second
      order chemometric tools were parallel factor analysis (PARAFAC), unfolded partial
      least-squares coupled to residual bilinearization (U-PLS/RBL), and
      multidimensional partial least-squares coupled to residual bilinearization (N
      PLS/RBL). The ability of U-PLS/RBL to successfully overcome spectral interference
      problems is demonstrated. The quality of the proposed method was established with
      the determination of galantamine in both artificial and natural water samples.

PMID- 20685475
TI  - Simultaneous determination of first-line anti-tuberculosis drugs by capillary
      zone electrophoresis using direct UV detection.
AB  - An alternative methodology for simultaneous analysis of ethambutol, isoniazid,
      rifampicin and pyrazinamide in pharmaceutical formulations by capillary zone
      electrophoresis under UV direct detection with an analysis time of 8.0 min is
      proposed. Background running was based on the effective mobility curve of the
      analytes and an optimum separation condition was achieved using a 3(3) Box
      Behnken design, with Brij 35, Cu(2+) and acetic acid/sodium acetate buffer as
      factors. An electrolyte consisting of 50.0 mmol L(-1) of acetic acid/sodium
      acetate buffer, 12.5 mmol L(-1) of CuSO(4), and standard and sample solutions
      prepared in 2.00 mmol L(-1) of Brij 35 and 12.5 mmol L(-1) of CuSO(4) were
      optimized. After evaluating validation parameters, the method was successfully
      applied to the analysis of samples in the form of tablets and sachets.

PMID- 20685476
TI  - Electrode modified with a composite film of ZnO nanorods and Ag nanoparticles as
      a sensor for hydrogen peroxide.
AB  - A conducting fluorine-doped tin oxide (FTO) electrode, first modified with zinc
      oxide nanorods (ZnONRs) and subsequently attached with photosynthesized silver
      nanoparticles (AgNPs), designated as AgNPs/ZnONRs/FTO electrode, was used as an
      amperometric sensor for the determination of hydrogen peroxide. The first layer
      (ZnONRs) was obtained by chemical bath deposition (CBD), and was utilized
      simultaneously as the catalyst for the photoreduction of Ag ions under UV
      irradiation and as the matrix for the immobilization of AgNPs. The aspect ratio
      of ZnONRs to be deposited was optimized by controlling the number of their CBDs
      to render enough surface area for Ag deposition, and the amount of AgNPs to be
      attached was controlled by adjusting the UV-irradiation time. The immobilized
      AgNPs showed excellent electrocatalytic response to the reduction of hydrogen
      peroxide. The resultant amperometric sensor showed 10-fold enhanced sensitivity
      for the detection of H(2)O(2), compared to that without AgNPs, i.e., only with a
      layer of ZnONRs. Amperometric determination of H(2)O(2) at -0.55 V gave a limit
      of detection of 0.9 microM (S/N=3) and a sensitivity of 152.1 mA M(-1) cm(-2) up
      to 0.983 mM, with a response time (steady-state, t(95)) of 30-40 s. The
      selectivity of the sensor was investigated against ascorbic acid (AA) and uric
      acid (UA). Energy dispersive X-ray (EDX) analysis, transmission electron
      microscopic (TEM) image, X-ray diffraction (XRD) patterns, cyclic voltammetry
      (CV), and scanning electron microscopic (SEM) images were utilized to
      characterize the modified electrode. Sensing properties of the modified electrode
      were studied both by CV and amperometric analysis.

PMID- 20685477
TI  - Separation and quantification of [RhCln(H2O)(6-n)](3-n) (n=0-6) complexes,
      including stereoisomers, by means of ion-pair HPLC-ICP-MS.
AB  - A hyphenated ion-pair (tetrabutylammonium chloride-TBACl) reversed phase (C(18))
      HPLC-ICP-MS method (High Performance Liquid Chromatography Inductively Coupled
      Plasma Mass Spectroscopy) for anionic Rh(III) aqua chlorido-complexes present in
      an HCl matrix has been developed. Under optimum chromatographic conditions it was
      possible to separate and quantify cationic Rh(III) complexes (eluted as a single
      band), [RhCl(3)(H(2)O)(3)], cis-[RhCl(4)(H(2)O)(2)](-), trans
      [RhCl(4)(H(2)O)(2)](-) and [RhCl(n)(H(2)O)(6-n)](3-n) (n=5, 6) species. The
      [RhCl(n)(H(2)O)(6-n)](3-n) (n=5, 6) complex anions eluted as a single band due to
      the relatively fast aquation of [RhCl(6)](3-) in a 0.1 mol L(-1) TBACl ionic
      strength mobile phase matrix. Moreover, the calculated t(1/2) of 1.3 min for
      [RhCl(6)](3-) aquation at 0.1 mol kg(-1) HCl ionic strength is significantly
      lower than the reported t(1/2) of 6.3 min at 4.0 mol kg(-1) HClO(4) ionic
      strength. Ionic strength or the activity of water in this context is a key
      parameter that determines whether [RhCl(n)(H(2)O)(6-n)](3-n) (n=5, 6) species can
      be chromatographically separated. In addition, aquation/anation rate constants
      were determined for [RhCl(n)(H(2)O)(6-n)](3-n) (n=3-6) complexes at low ionic
      strength (0.1 mol kg(-1) HCl) by means of spectrophotometry and independently
      with the developed ion-pair HPLC-ICP-MS technique for species assignment
      validation. The Rh(III) samples that was equilibrated in differing HCl
      concentrations for 2.8 years at 298K was analyzed with the ion-pair HPLC method.
      This analysis yielded a partial Rh(III) aqua chlorido-complex species
      distribution diagram as a function of HCl concentration. For the first time the
      distribution of the cis- and trans-[RhCl(4)(H(2)O)(2)](-) stereoisomers have been
      obtained. Furthermore, it was found that relatively large amounts of 'highly'
      aquated [RhCl(n)(H(2)O)(6-n)](3-n) (n=0-4) species persist in up to 2.8 mol L(-1)
      HCl and in 1.0 mol L(-1) HCl the abundance of the [RhCl(5)(H(2)O)](2-) species is
      only 8-10% of the total, far from the 70-80% as previously proposed. A 95%
      abundance of the [RhCl(6)](3-) complex anion occurs only when the HCl
      concentration is above 6 mol L(-1). The detection limit for a Rh(III) species
      eluted from the column is below 0.147 mg L(-1).

PMID- 20685478
TI  - Ultrasound-assisted leaching-dispersive solid-phase extraction followed by liquid
      liquid microextraction for the determination of polybrominated diphenyl ethers in
      sediment samples by gas chromatography-tandem mass spectrometry.
AB  - Ultrasound-assisted leaching-dispersive solid-phase extraction followed by
      dispersive liquid-liquid microextraction (USAL-DSPE-DLLME) technique has been
      developed as a new analytical approach for extracting, cleaning up and
      preconcentrating polybrominated diphenyl ethers (PBDEs) from sediment samples
      prior gas chromatography-tandem mass spectrometry (GC-MS/MS) analysis. In the
      first place, PBDEs were leached from sediment samples by using acetone. This
      extract was cleaned-up by DSPE using activated silica gel as sorbent material.
      After clean-up, PBDEs were preconcentrated by using DLLME technique. Thus, 1 mL
      acetone extract (disperser solvent) and 60 microL carbon tetrachloride
      (extraction solvent) were added to 5 mL ultrapure water and a DLLME technique was
      applied. Several variables that govern the proposed technique were studied and
      optimized. Under optimum conditions, the method detection limits (MDLs) of PBDEs
      calculated as three times the signal-to-noise ratio (S/N) were within the range
      0.02-0.06 ng g(-1). The relative standard deviations (RSDs) for five replicates
      were <9.8%. The calibration graphs were linear within the concentration range of
      0.07-1000 ng g(-1) for BDE-47, 0.09-1000 ng g(-1) for BDE-100, 0.10-1000 ng g(-1)
      for BDE-99 and 0.19-1000 ng g(-1) for BDE-153 and the coefficients of estimation
      were > or =0.9991. Validation of the methodology was carried out by standard
      addition method at two concentration levels (0.25 and 1 ng g(-1)) and by
      comparing with a reference Soxhlet technique. Recovery values were > or =80%,
      which showed a satisfactory robustness of the analytical methodology for
      determination of low PBDEs concentration in sediment samples.

PMID- 20685479
TI  - Amine-terminated organosilica nanosphere functionalized Prussian blue for the
      electrochemical detection of glucose.
AB  - A new glucose biosensor had been developed by immobilizing positively charged
      gold nanoparticles (PGNs) on organosilica nanosphere functionalized Prussian blue
      (OSiFPB)-modified gold electrode. The OSiFPB compound could not only effectively
      prevent the leakage of the PB mediator during measurements, but also easily form
      stable film on the electrode surface with efficient redox-activity and excellent
      conductivity. Furthermore, with the negatively charged surface of OSiFPB, this
      film could be used as an interface to adsorb the PGNs, which provided a congenial
      microenvironment for adsorbing biomolecules and decreased the electron-transfer
      impedance. So, with glucose oxidase as a model biomolecular, the proposed sensor
      showed rapid and highly sensitive amperometric response to glucose and this
      immobilization approach effectively improved the stability of the electron
      transfer mediator. This work would be promising for construction of biosensor and
      bioelectronic devices.

PMID- 20685480
TI  - Graphene enhanced electrochemiluminescence of CdS nanocrystal for H2O2 sensing.
AB  - Graphene-CdS (G-CdS) nanocomposites were successfully prepared by CdS
      nanocrystals (CdS NCs) formed in situ on the surface of graphene sheets, using
      graphene oxide (GO) sheets with rich negatively charged carboxylic acid groups as
      starting materials. Compared with pure CdS NCs, the presence of the graphene
      doped in G-CdS nanocomposites could facilitate the electrochemical redox process
      of CdS NCs; further, the as-prepared G-CdS nanocomposite can react with H(2)O(2)
      to generate strong and stable electrochemiluminescent (ECL) emission, which not
      only enhances its ECL intensity by about 4.3-fold but also decreases its onset
      potential for about 320 mV. The as-prepared solid-state ECL H(2)O(2) sensor shows
      acceptable linear response from 5 microM up to 1mM with a detection limit of 1.7
      microM (S/N=3). The ECL H(2)O(2) sensor exhibits excellent reproducibility and
      long-term stability. Such a property would promote the potential application of
      the graphene as enhanced materials in fabricating sensors for chemical and
      biochemical analysis.

PMID- 20685481
TI  - beta-cyclodextrins-based inclusion complexes of CoFe(2)O(4) magnetic
      nanoparticles as catalyst for the luminol chemiluminescence system and their
      applications in hydrogen peroxide detection.
AB  - beta-cyclodextrins (beta-CD)-based inclusion complexes of CoFe(2)O(4) magnetic
      nanoparticles (MNPs) were prepared and used as catalysts for chemiluminescence
      (CL) system using the luminol-hydrogen peroxide CL reaction as a model. The as
      prepared inclusion complexes were characterized by XRD (X-ray diffraction), TGA
      (thermal gravimetric analysis) and FT-IR. The oxidation reaction between luminol
      and hydrogen peroxide in basic media initiated CL. The effect of beta-CD-based
      inclusion complexes of CoFe(2)O(4) magnetic nanoparticles and naked CoFe(2)O(4)
      magnetic nanoparticles on the luminol-hydrogen peroxide CL system was
      investigated. It was found that inclusion complexes between beta-CD and
      CoFe(2)O(4) magnetic nanoparticles could greatly enhance the CL of the luminol
      hydrogen peroxide system. Investigation on the kinetic curves and the
      chemiluminescence spectra of the luminol-hydrogen peroxide system demonstrates
      that addition of CoFe(2)O(4) MNPs or inclusion complexes between beta-CD and
      CoFe(2)O(4) MNPs does not produce a new luminophor of the chemiluminescent
      reaction. The luminophor for the CL system was still the excited-state 3
      aminophthalate anions (3-APA*). The enhanced CL signals were thus ascribed to the
      possible catalysis from CoFe(2)O(4) MNPs or inclusion complexes between beta-CD
      and CoFe(2)O(4) nanoparticles. The feasibility of employing the proposed system
      for hydrogen peroxide sensing was also investigated. Experimental results showed
      that the CL emission intensity was linear with hydrogen peroxide concentration in
      the range of 1.0 x 10(-7) to 4.0 x 10(-6) mol L(-1) with a detection limit of 2.0
      x 10(-8) mol L(-1) under optimized conditions. The proposed method has been used
      to determine hydrogen peroxide in water samples successfully.

PMID- 20685482
TI  - A column-switching method for quantification of the enantiomers of omeprazole in
      native matrices of waste and estuarine water samples.
AB  - This work reports the use of a two-dimensional liquid chromatography (2D-LC)
      system for quantification of the enantiomers of omeprazole in distinct native
      aqueous matrices. An octyl restricted-access media bovine serum albumin column
      (RAM-BSA C(8)) was used in the first dimension, while a polysaccharide-based
      chiral column was used in the second dimension with either ultraviolet (UV-vis)
      or ion-trap tandem mass spectrometry (IT-MS/MS) detection. An in-line
      configuration was employed to assess the exclusion capacity of the RAM-BSA
      columns to humic substances. The excluded macromolecules had a molecular mass in
      the order of 18 kDa. Good selectivity, extraction efficiency, accuracy, and
      precision were achieved employing a very small amount (500 microL or 1.00 mL) of
      native water sample per injection, with detection limits of 5.00 microg L(-1),
      using UV-vis, and 0.0250 microg L(-1), using IT-MS/MS. The total analysis time
      was only 35 min, with no time spent on sample preparation. The methods were
      successfully applied to analyze a series of waste and estuarine water samples.
      The enantiomers were detected in an estuarine water sample collected from the
      Douro River estuary (Portugal) and in an influent sample from the wastewater
      treatment plant (WWTP) of Sao Carlos (Brazil). As far as we are concerned, this
      is the first report of the occurrence of (+)-omeprazole and (-)-omeprazole in
      native aqueous matrices.

PMID- 20685483
TI  - Carbon nuclear magnetic resonance spectroscopic fingerprinting of commercial
      gasoline: pattern-recognition analyses for screening quality control purposes.
AB  - In this work, the combination of carbon nuclear magnetic resonance ((13)C NMR)
      fingerprinting with pattern-recognition analyses provides an original and
      alternative approach to screening commercial gasoline quality. Soft Independent
      Modelling of Class Analogy (SIMCA) was performed on spectroscopic fingerprints to
      classify representative commercial gasoline samples, which were selected by
      Hierarchical Cluster Analyses (HCA) over several months in retails services of
      gas stations, into previously quality-defined classes. Following optimized (13)C
      NMR-SIMCA algorithm, sensitivity values were obtained in the training set
      (99.0%), with leave-one-out cross-validation, and external prediction set
      (92.0%). Governmental laboratories could employ this method as a rapid screening
      analysis to discourage adulteration practices.

PMID- 20685484
TI  - Electrochemical behavior of atomoxetine and its voltammetric determination in
      capsules.
AB  - In this work, the electrochemical behavior and the analytical application of
      atomoxetine, a selective noradrenaline reuptake inhibitor, are studied.
      Atomoxetine, studied by differential pulse voltammetry and cyclic voltammetry on
      a glassy carbon electrode, exhibited an anodic response in aqueous media with pH
      between 1.5 and 7. In non-aqueous medium (acetonitrile), the drug exhibited two
      irreversible oxidation peaks that are diffusion controlled. From
      chronocoulometric studies in acetonitrile, it was determined that each oxidation
      signal involves two and four electrons, respectively. For analytical purposes, a
      differential pulse voltammetry technique in 0.1 mol L(-1) perchloric acid was
      selected, which exhibited adequate figures of merit. The percent recovery was
      96.6+/-1.2 and the detection and quantitation limits were 6.9 x 10(-5) and 1.0 x
      10(-4) mol L(-1), respectively. Also, results indicate that excipients do not
      interfere with the oxidation signal of atomoxetine, which leads to the conclusion
      that the developed method is satisfactorily selective for atomoxetine
      quantification in pharmaceuticals with no prior separation or extraction
      necessary. Finally, the proposed voltammetric method was successfully applied to
      both the assay and the uniformity content of atomoxetine in capsules. For
      comparison, high-performance liquid chromatography analysis was also performed.

PMID- 20685485
TI  - A facile and efficient strategy for one-step in situ preparation of hydrophobic
      organic monolithic stationary phases by click chemistry and its application on
      protein separation.
AB  - A simple one-step in situ "click" modification strategy was developed for the
      preparation of hydrophobic organic monolithic columns for the first time. The
      column morphology and surface chemistry of the fabricated monolithic columns were
      characterized by scanning electron microscopy, Fourier transform infrared
      spectroscopy and X-ray photoelectron spectroscopy, respectively. The
      chromatographic performances of the C8/C18 "click" monoliths were evaluated
      through the separation of a mixture of five proteins such as ribonuclease A,
      soybean trypsin inhibitor, cytochrome c, bovine haemoglobin and bovine serum
      albumin. Compared with the blank column, the higher hydrophobicity stationary
      phases obtained from the "clicked" modification have longer retention times and
      higher resolution for the five proteins. The separation of five proteins mixture
      on click C18 monolith with gradient elution at different flow rates was also
      investigated, the baseline separation of five proteins could be achieved at three
      different flow rates.

PMID- 20685486
TI  - Novel facile detection of persistent organic pollutants using highly sensitive
      gas sensor.
AB  - Persistent organic pollutants (POPs) are greatly noxious chemicals in
      environment, and they can cumulate in organisms and transfer between different
      species. Therefore, it is significant to detect POPs for both environmental
      evaluation and further treatment. However, developing facile approach for the
      detection of POPs still remains a challenge so far. In this paper, we report an
      innovative method for facile detection of POPs using gas sensor for the first
      time. Porous SnO(2) nanostructures with a special tri-walled structure prepared
      via hydrothermal route and annealing process, were employed as gas-sensing
      materials. Through gas measurements, it was revealed that the as-fabricated gas
      sensor exhibited highly sensitive performance towards target POPs, including
      methoxychlor, mirex, p,p'-DDT, and aldrin. Moreover, we found that target POPs
      were distinguishable by extracting characteristics in kinetic curves of gas
      adsorption-desorption. As the presented detecting approach is facile without the
      requirements of complex operations, expensive and bulky instruments, it is
      expected that it would be developed as a promising method for the detection of
      POPs, and thereby showing its significance for environmental monitoring.

PMID- 20685487
TI  - One-pot electrosynthesis of polyglycine-like thin film on platinum electrodes as
      transducer for solid state pH measurements.
AB  - The anodic oxidation of concentrated glycine based aqueous electrolyte on smooth
      platinum electrode leads to a strongly grafted polyglycine-like coating on the
      surface in an irreversible way. Due to the proton affinity towards amino groups
      of polyglycine (PG), the electrodeposited thin film was used as receptor for
      solid potentiometric pH sensor. In order to reach local pH measurement, we
      developed miniaturized microelectrodes on glass substrate thanks to
      photolithography process. We used silver chloride on silver as the reference
      electrode. The couple (silver chloride, PG based platinum electrode) of
      microelectrodes gives linear potentiometric response vs. pH in the range [2-12],
      reversibly and with a sensitivity of 52.4 mV/pH (for 1mm electrode size). PG
      based pH electrode is compared to other organic polymer based pH receptor such as
      linear polyethylenimine (L-PEI), polyaniline (PANI) and glass membrane.

PMID- 20685488
TI  - A concept of dual optical detection using three light emitting diodes.
AB  - In this paper a concept of very simple measurement system dedicated for
      simultaneous photometric and fluorometric detection is presented. Only three
      ordinary unmodified light emitting diodes (LEDs) can be applied in this
      analytical device: one of them is used in the conventional way as a source of
      nearly monochromatic light inducing fluorescence, whereas two others are applied
      as photometric and fluorometric detectors of light. In this study quinine is
      chosen as a model analyte. The reported device enables simultaneous detection of
      this analyte in the micromolar range of concentration. The practical utility of
      prototype dual detector for complex sample analysis is illustrated by its
      application for determination of quinine in tonic water samples.

PMID- 20685489
TI  - Application of an immobilised amylose-based chiral stationary phase to the
      development of new monoamine oxidase B inhibitors.
AB  - A direct HPLC enantioseparation of three new chiral oxadiazoline derivatives
      endowed with potential MAO-B inhibitory activity was accomplished on the
      immobilised Chiralpak IA chiral stationary phase. Multi-mg amounts of enantiomers
      with high enantiomeric purity (ee> or =98%) were rapidly collected using pure
      dichloromethane as eluent. The absolute configuration and chiroptical properties
      of the enantiomers isolated at semipreparative scale were exhaustively
      determined.

PMID- 20685490
TI  - A simple and rapid competitive enzyme-linked immunosorbent assay (cELISA) for
      high-throughput measurement of secretory immunoglobulin A (sIgA) in saliva.
AB  - A simple competitive enzyme-linked immunosorbent assay (cELISA) was established
      for rapid measurement of secretory immunoglobulin A (sIgA) in saliva. The method
      was based on competitive reaction between the immobilized IgA and free IgA in the
      solution for the limited amount of horseradish peroxidase-conjugated rabbit anti
      human IgA. In comparison with the conventionally used Sandwich ELISA, the cELISA
      is simpler, low-cost, and shows better reproducibility since it is not affected
      by the variation of capture antibodies from different batches. The assay time was
      also significantly reduced from more than 5h to less than 3h. Different curve
      fitting models were compared, among which the fully specified logit-log model
      gave the best results. The linear working range and limit of detection were found
      to be 0.1-100 microg mL(-1) and 0.05 microg mL(-1), respectively. Matrix effects
      of saliva samples were investigated and a reasonable range of dilution factors
      were proposed. The developed method offers a very practical approach for high
      throughput measurement of sIgA in saliva samples.

PMID- 20685491
TI  - Supplemental calcium in the chemoprevention of colorectal cancer: a systematic
      review and meta-analysis.
AB  - OBJECTIVE: The aim of the review was to assess the evidence for the effectiveness
      of calcium in reducing the recurrence of adenomas and the occurrence of
      colorectal cancer among populations at high, intermediate, and low risk of the
      disease. METHODS: A systematic review of randomized controlled trials (RCTs) was
      performed to compare calcium alone, and with other agents, versus placebo. Nine
      databases (Cochrane Library, MEDLINE, PreMEDLINE, CINAHL, EMBASE, Web of Science,
      Biological Abstracts, the National Research Register, and Current Controlled
      Trials) were searched for published and unpublished trials. Searches were not
      restricted by either language or date of publication. All searches were completed
      in January 2010. Database thesaurus and free text terms for calcium and adenomas
      or colorectal cancer were used to search for trial reports; additional terms were
      used to search for other agents of interest, such as NSAIDs and folic acid.
      Search terms consisted of a combination of terms for colorectal cancer (eg, colon
      or colorectal and neoplasm or cancer or adenoma) and terms for calcium and RCTs.
      The initial searches were conducted in June 2008, with update searches in January
      2010 to identify more recent studies. The reference lists of relevant studies
      were also searched for additional papers not identified by the search of
      electronic databases. Studies had to satisfy the following criteria to be
      included: RCTs about calcium, with or without other chemopreventive agents, in
      adults with familial adenomatous polyposis (FAP), hereditary nonpolyposis
      colorectal cancer, or a history of colorectal adenomas, or with no increased
      baseline risk of colorectal cancer. Meta-analysis was performed. For discrete and
      numerical outcomes, relative risks (RRs) and risk differences were reported with
      95% CIs. The random-effects model was used to account for clinical and
      methodologic variations between trials. RESULTS: The original and update searches
      of electronic databases produced 3835 citations, of which 6 studies (8 papers)
      met the inclusion criteria. Supplemental calcium had no effect on the number of
      adenomas in 1 small trial of patients with FAP. Meta-analysis of 3 trials in
      individuals with a history of adenomas showed a statistically significant
      reduction in the RR for adenoma recurrence (RR = 0.80 [95% CI, 0.69-0.94], P =
      0.006) for those receiving calcium 1200 to 2000 mg/d, but no effect was seen in
      advanced adenoma (RR = 0.77 [95% CI, 0.501.17], P = NS). Meta-analysis of 2
      trials in populations with no increased baseline risk for colorectal cancer
      suggested that calcium, with or without vitamin D, had no effect on the RR for
      colorectal cancer (RR = 0.62 [95% CI, 0.11-3.40], P = NS). CONCLUSION: Published
      reports indicated that supplemental calcium was effective for the prevention of
      adenoma recurrence in populations with a history of adenomas, but no similar
      effect was apparent in populations at higher or lower risk.

PMID- 20685492
TI  - Treatment options for patients with chronic myeloid leukemia who are resistant to
      or unable to tolerate imatinib.
AB  - BACKGROUND: Imatinib has been found to substantially improve outcomes in patients
      with chronic myeloid leukemia (CML) compared with previously available therapies.
      However, its use is complicated by development of resistance or drug intolerance,
      prompting dose escalation or a trial of dasatinib or nilotinib, the second
      generation tyrosine kinase inhibitors (TKIs). OBJECTIVES: This article reviews
      the mechanisms of TKI resistance; discusses the tolerability and efficacy of high
      dose imatinib, dasatinib, and nilotinib; and provides background for the rational
      use of second-line treatment options. METHODS: MEDLINE (1966-December 2009) and
      EMBASE (1993-December 2009) were searched for pertinent English-language
      publications using search terms that included, but were not limited to, chronic
      myeloid leukemia, imatinib, dasatinib, nilotinib, and clinical trial. Abstracts
      from American Society of Hematology annual meetings (2005-2009) were also
      reviewed. There were no prespecified inclusion or exclusion criteria. RESULTS:
      Major and complete cytogenetic responses (MCyR and CCyR, respectively) to second
      line treatment with high-dose (600-800 mg/d PO) imatinib were restricted to CML
      patients who had achieved a CyR to standard-dose imatinib: >90% of patients
      without a previous CyR failed to respond. The expected durability of the response
      to this approach remains unclear. Grade 3/4 thrombocytopenia, neutropenia, and
      anemia occurred in 14%, 39%, and 8%, respectively, of patients receiving high
      dose imatinib. In patients who failed first-line treatment with imatinib,
      dasatinib (70 mg BID PO) was associated with higher rates of CCyR at 2 years
      compared with imatinib (44% vs 18%, respectively; P = 0.003), as well as higher
      estimated rates of progression-free survival at 2 years (86% vs 65%; P = 0.001).
      Dasatinib use was complicated by grade 3/4 thrombocytopenia and neutropenia in
      57% and 63% of patients, respectively, and pleural effusion in 5%. Nilotinib
      treatment was effective in patients who were resistant to or unable to tolerate
      imatinib, with 46% and 58% achieving a CCyR and MCyR, respectively, at 2 years.
      Nilotinib use was complicated by grade 3/4 thrombocytopenia and neutropenia in
      28% and 40% of patients, respectively, and QTc-interval prolongation in 1% to 10%
      of patients. Neither agent was clinically effective in patients with the common
      T315I mutation. CONCLUSION: Dasatinib and nilotinib were effective and generally
      well tolerated as second-line treatments for CML patients with a suboptimal
      response to standard doses of imatinib or imatinib intolerance.

PMID- 20685493
TI  - Plerixafor: A chemokine receptor-4 antagonist for mobilization of hematopoietic
      stem cells for transplantation after high-dose chemotherapy for non-Hodgkin's
      lymphoma or multiple myeloma.
AB  - BACKGROUND: Autologous hematopoietic stem cell (HSC) transplantation is used to
      facilitate hematopoietic recovery after administration of high-dose chemotherapy
      in patients with Hodgkin's disease, non-Hodgkin's lymphoma (NHL), multiple
      myeloma (MM), leukemias, and some solid tumors. There are limitations to the
      existing methods of mobilizing CD34+ HSC with chemotherapy and/or granulocyte
      colony-stimulating factor (G-CSF). Plerixafor, a bicyclam molecule that acts as a
      pure antagonist of chemokine receptor-4, is approved by the US Food and Drug
      Administration for use in combination with G-CSF for mobilization of CD34+ HSC in
      patients with NHL or MM. OBJECTIVE: This review presents information on
      plerixafor, including its mechanism of action in mobilizing stem cells,
      pharmacokinetics, clinical efficacy, adverse effects, and pharmacoeconomic
      considerations. METHODS: MEDLINE, EMBASE (1996-June 2009), and International
      Pharmaceutical Abstracts (1970-June 2009) were searched on July 9, 2009, using
      the key words plerixafor and AMD3100 for reports relating to HSC mobilization.
      The search was updated on September 20, 2009, and again on January 30, 2010. The
      reference lists of identified articles were examined for additional abstracts and
      other sources of information. The journal Blood was searched online to identify
      abstracts presented at Annual Meetings of the American Society of Hematology.
      RESULTS: After administration of plerixafor, HSC migrate from the bone marrow
      into the peripheral blood, permitting collection by apheresis. Clinical trials in
      humans have found that the combination of G-CSF + plerixafor facilitates
      mobilization of HSC. In patients with MM without extensive previous treatment who
      were undergoing a first mobilization, the use of G-CSF + plerixafor was reported
      to double counts of circulating peripheral CD34+ HSC and thus double the number
      of CD34+ HSC collected in half as many apheresis procedures, although rates of
      engraftment, graft durability, transplantation, and survival outcomes were not
      significantly improved. In patients with Hodgkin's disease or NHL, in whom
      limited success in mobilization is expected, G-CSF + plerixafor also facilitated
      or improved mobilization with improved apheresis yields, again without
      significant improvement in outcomes. Common (> or = 20%) adverse events of
      plerixafor used in combination with G-CSF include diarrhea (37%), nausea (34%),
      injection-site reactions (34%), fatigue (27%), and headache (22%). Plerixafor
      0.24 mg/kg SC is administered on the evening of the fourth day of G-CSF dosing,
      approximately 11 hours before the first apheresis session. Daily doses of
      plerixafor can be repeated up to 3 times on consecutive days to achieve adequate
      HSC collection. The average wholesale price of a 24-mg vial of plerixafor is
      $7500. CONCLUSIONS: Plerixafor is an effective agent for mobilizing CD34+ HSC.
      Long-term treatment outcomes are being studied in patients undergoing autologous
      transplantation of HSC mobilized with G-CSF + plerixafor.

PMID- 20685494
TI  - Buprenorphine transdermal system in adults with chronic low back pain: a
      randomized, double-blind, placebo-controlled crossover study, followed by an open
      label extension phase.
AB  - BACKGROUND: Buprenorphine is a mixed-activity, partial mu-opioid agonist. Its
      lipid solubility makes it well suited for transdermal administration. OBJECTIVE:
      This study assessed the efficacy and safety profile of a 7-day buprenorphine
      transdermal system (BTDS) in adult (age >18 years) patients with moderate to
      severe chronic low back pain previously treated with > or =1 tablet daily of an
      opioid analgesic. METHODS: This was a randomized, double-blind, placebo
      controlled crossover study, followed by an open-label extension phase. After a 2-
      to 7-day washout of previous opioid therapy, eligible patients were randomized to
      receive BTDS 10 microg/h or matching placebo patches. The dose was titrated
      weekly using 10- and 20-microg/h patches (maximum, 40 microg/h) based on efficacy
      and tolerability. After 4 weeks, patients crossed over to the alternative
      treatment for another 4 weeks. Patients who completed the double-blind study were
      eligible to enter the 6-month open-label phase. Rescue analgesia was provided as
      acetaminophen 325 mg to be taken as 1 or 2 tablets every 4 to 6 hours as needed.
      The primary outcome assessments were daily pain intensity, measured on a 100-mm
      visual analog scale (VAS), from no pain to excruciating pain, and a 5-point
      ordinal scale, from 0 = none to 4 = excruciating. Secondary outcome assessments
      included the Pain and Sleep Questionnaire (100-mm VAS, from never to always),
      Pain Disability Index (ordinal scale, from 0 = no disability to 11 = total
      disability), Quebec Back Pain Disability Scale (categorical scale, from 0 = no
      difficulty to 5 = unable to do), and the 36-item Short Form Health Survey (SF
      36). Patients and investigators assessed overall treatment effectiveness at the
      end of each phase; they assessed treatment preference at the end of double-blind
      treatment. After implementation of a precautionary amendment, the QTc interval
      was measured 3 to 4 days after randomization and after any dose adjustment. All
      assessments performed during the double-blind phase were also performed every 2
      months during the open-label extension. Adverse events were collected by non
      directed questioning throughout the study. RESULTS: Of 78 randomized patients, 52
      (66.7%) completed at least 2 consecutive weeks of treatment in each study phase
      without major protocol violations (per-protocol [PP] population: 32 women, 20
      men; mean [SD] age, 51.3 [11.4] years; mean weight, 85.5 [19.5] kg; 94% white, 4%
      black, 2% other). The mean (SD) dose of study medication during the last week of
      treatment was 29.8 (12.1) microg/h for BTDS and 32.9 (10.7) microg/h for placebo
      (P = NS). During the last week of treatment, BTDS was associated with
      significantly lower mean (SD) pain intensity scores compared with placebo on both
      the VAS (45.3 [21.3] vs 53.1 [24.3] mm, respectively; P = 0.022) and the 5-point
      ordinal scale (1.9 [0.7] vs 2.2 [0.8]; P = 0.044). The overall Pain and Sleep
      score was significantly lower with BTDS than with placebo (177.6 [125.5] vs 232.9
      [131.9]; P = 0.027). There were no treatment differences on the Pain Disability
      Index, Quebec Back Pain Disability Scale, or SF-36; however, BTDS was associated
      with significant improvements compared with placebo on 2 individual Quebec Back
      Pain Disability Scale items (get out of bed: P = 0.042; sit in a chair for
      several hours: P = 0.022). Of the 48 patients/physicians in the PP population who
      rated the effectiveness of treatment, 64.6% of patients (n = 31) rated BTDS
      moderately or highly effective, as did 62.5% of investigators (n = 30). Among the
      50 patients in the PP population who answered the preference question, 66.0% of
      patients (n = 33) preferred the phase in which they received BTDS and 24.0% (n =
      12) preferred the phase in which they received placebo (P = 0.001), with the
      remainder having no preference; among investigators, 60.0% (n = 30) and 28.0% (n
      = 14) preferred the BTDS and placebo phases, respectively (P = 0.008), with the
      remainder having no preference. The mean placebo-adjusted change from baseline in
      the QTc interval ranged from -0.8 to +3.8 milliseconds (P = NS). BTDS treatment
      was associated with a significantly higher frequency of nausea (P < 0.001),
      dizziness (P < 0.001), vomiting (P = 0.008), somnolence (P = 0.020), and dry
      mouth (P = 0.003), but not constipation. Of the 49 patients completing 8 weeks of
      double-blind treatment, 40 (81.6%) entered the 6-month, open-label extension
      study and 27 completed it. Improvements in pain scores achieved during the double
      blind phase were maintained in these patients. CONCLUSIONS: In the 8-week, double
      blind portion of this study, BTDS 10 to 40 microg/h was effective compared with
      placebo in the management of chronic, moderate to severe low back pain in
      patients who had previously received opioids. The improvements in pain scores
      were sustained throughout the 6-month, open-label extension. (Current Controlled
      Trials identification number: ISRCTN 06013881).

PMID- 20685495
TI  - Effects of combination olmesartan medoxomil plus azelnidipine versus monotherapy
      with either agent on 24-hour ambulatory blood pressure and pulse rate in Japanese
      patients with essential hypertension: additional results from the REZALT study.
AB  - BACKGROUND: In a previously reported randomized, double-blind, parallel-group
      study of the efficacy and tolerability of olmesartan medoxomil (OLM) and
      azelnidipine (AZL) combination therapy compared with monotherapy with each agent
      in Japanese patients with essential hypertension (the REZALT study), the use of a
      combination of OLM, an angiotensin II receptor blocker, plus AZL, a
      dihydropyridine calcium channel blocker, was associated with significantly
      greater reductions in office sitting blood pressure (BP) and 24-hour ambulatory
      BP compared with monotherapy with either agent, and was well tolerated.
      OBJECTIVE: This article reports the results from an a priori planned analysis and
      post hoc analyses of the diurnal BP and pulse rate (PR) profiles of OLM/AZL
      versus monotherapy with either agent from the REZALT study. METHODS: Male and
      female Japanese outpatients with essential hypertension were eligible if they met
      the following inclusion criteria: age > or = 20 years; systolic BP (SBP) > or =
      140 to <180 mm Hg and diastolic BP (DBP) > or = 90 to <110 mm Hg; and 24-hour
      ambulatory SBP/DBP > or = 135/> or = 80 mm Hg. Patients were randomly assigned to
      receive OLM/AZL 10/8 mg, OLM/AZL 20/16 mg, OLM 20 mg, or AZL 16 mg, once daily
      for 12 weeks. The effectiveness of the treatments was assessed using 24-hour
      ambulatory BP monitoring (ABPM) and PR, analyzed by time period (BP and PR, 24
      hours, daytime [7 AM-<10 PM], nighttime [10 PM-<7 AM], and early morning [6 AM-<9
      AM]; PR, morning [6 AM -<11 AM]) and dipping status at baseline (dippers
      [(Daytime BP - Nighttime BP)/Daytime BP > or = 10%] or nondippers [(Daytime BP -
      Nighttime BP)/Daytime BP <10%]). RESULTS: A total of 867 patients were enrolled,
      and 862 randomized patients were included in the full analysis set (590 men, 272
      women; mean age, 56.6 years). A total of 839 patients had assessable ABPM data
      (213, 211, 206, and 209 patients in the OLM/AZL 10/8 mg, OLM/AZL 20/16 mg, OLM,
      and AZL groups, respectively). No clinically significant between-group
      differences were observed in baseline demographic and clinical characteristics.
      Combination therapy was associated with significantly greater antihypertensive
      effects on 24-hour ABPM compared with either monotherapy in all of the time
      periods, as follows: SBP/DBP reductions with OLM/AZL 20/16 mg in the daytime,
      nighttime, and early morning were -22.6/-14.1, -21.2/-12.5, and -20.6/-11.9 mm
      Hg, respectively (all, P < 0.05 vs the other 3 treatment groups). The SBP/DBP
      reductions with OLM/AZL 10/8 mg (daytime, -18.2/-11.0 mm Hg; nighttime, -18.1/
      10.0 mm Hg; and early morning, -15.6/-9.3 mm Hg) were also significantly greater
      than with OLM 20 mg (-11.8/-6.7, -12.8/-7.2, and -11.0/ -6.9 mm Hg, respectively;
      all, P < 0.01) and AZL 16 mg (-13.1/-7.8, -10.2/-5.5, and -9.9/-6.1 mm Hg; all, P
      < 0.001) in all of the time periods. The antihypertensive effects associated with
      OLM/AZL 10/8 mg or 20/16 mg were significantly greater than those with
      monotherapies regardless of dipping pattern at baseline (all, P < 0.05) in all of
      the time periods, with the exception of nighttime reduction with OLM/AZL 10/8 mg
      versus OLM in dippers. The numbers of patients who had any increase in BP were
      12/213 (5.6%) with OLM/AZL 10/8 mg, 13/211 (6.2%) with OLM/AZL 20/16 mg, 35/206
      (17.0%) with OLM, and 36/209 (17.2%) with AZL. The AZL-containing regimens were
      associated with reduced morning PR (mean [95% CI] changes from baseline to week
      12: -1.5 beats/min [-2.5 to -0.4] with OLM/AZL 10/8 mg, -2.1 beats/min [-3.0 to 
      1.1] with OLM/AZL 20/16 mg, 0.4 beat/min [-0.5 to 1.3] with OLM, and -1.9
      beats/min [-2.8 to -1.0] with AZL). CONCLUSION: In this study in Japanese
      patients with essential hypertension, the reductions in daytime, nighttime, and
      early-morning BP assessed using 24-hour ABPM were significantly greater with
      combination OLM/AZL than with either monotherapy, regardless of dipping pattern
      at baseline. Japan Pharmaceutical Information Center registration number:
      JapicCTI-060286.

PMID- 20685496
TI  - Comparison of the analgesic efficacy of concurrent ibuprofen and paracetamol with
      ibuprofen or paracetamol alone in the management of moderate to severe acute
      postoperative dental pain in adolescents and adults: a randomized, double-blind,
      placebo-controlled, parallel-group, single-dose, two-center, modified factorial
      study.
AB  - BACKGROUND: Combination analgesics may offer improved analgesic efficacy,
      particularly for moderate to severe pain. OBJECTIVE: This study evaluated the
      analgesic benefits of concurrent ibuprofen and paracetamol compared with each
      drug used alone in the management of acute postoperative dental pain. METHODS:
      Healthy patients aged 16 to 40 years undergoing surgical removal of 3 to 4
      impacted molars (total impaction score > or = 9) were enrolled in this
      randomized, double-blind, placebo-controlled, parallel-group, single-dose, 2
      center, modified factorial US study. Patients were randomly assigned in a ratio
      of 2:1:2:1:1 to ibuprofen 400 mg/paracetamol 1000 mg, ibuprofen 200
      mg/paracetamol 500 mg, ibuprofen 400 mg, paracetamol 1000 mg, or placebo when
      postoperative pain reached moderate to severe intensity. The primary efficacy end
      point was the sum of pain relief and pain intensity differences from 0 to 8 hours
      (SPRID8). Several secondary end points were also measured, including total pain
      relief (TOTPAR), sum of pain intensity differences (SPID), and SPID on the visual
      analog scale (SPID VAS) at various time points. Other analgesic efficacy measures
      included peak effect, onset and duration of effect, and patients' overall
      assessment of treatment. The tolerability of study medications was assessed in
      terms of the frequency and nature of adverse events, which were assessed with
      standard questions, as well as changes from baseline in vital signs. RESULTS: A
      total of 234 patients were randomly assigned to treatment and included in the
      intent-to- treat population. The patients were predominantly female (74.4%
      [174/234]) and white (76.5% [179/234]); mean (SD) age was 20.8 (3.1) years and
      weight was 69.1 (16.5) kg. For SPRID8, the group treated with ibuprofen 400
      mg/paracetamol 1000 mg had significantly better mean scores compared with
      ibuprofen alone (P < 0.001), paracetamol alone (P < 0.001), and ibuprofen 200
      mg/paracetamol 500 mg (P = 0.02). The group taking ibuprofen 200 mg/paracetamol
      500 mg achieved significantly better mean SPRID8 scores than paracetamol alone (P
      = 0.03), but not ibuprofen alone (P = NS). Ibuprofen 400 mg/paracetamol 1000 mg
      was associated with significantly better scores than was single-agent therapy for
      TOTPAR, SPID, and SPID VAS at all time intervals and for SPRID from 4 to 6 hours
      (all, P < 0.001). Pairwise comparisons found statistically significant
      differences in favor of all active treatments versus placebo for virtually all
      efficacy end points, thereby supporting assay sensitivity. Adverse events were
      similar across treatments; the most frequent were nausea (26.1% [61/234]),
      vomiting (18.8% [44/234]), headache (10.3% [24/234]), and dizziness (8.1%
      [19/234]). CONCLUSION: Concurrent ibuprofen and paracetamol appeared to provide
      significantly better analgesic efficacy compared with ibuprofen or paracetamol
      alone for acute postoperative dental pain in these adolescents and adults.

PMID- 20685497
TI  - Randomized, open-label, parallel-group evaluations of basal-bolus therapy versus
      insulin lispro premixed therapy in patients with type 2 diabetes mellitus failing
      to achieve control with starter insulin treatment and continuing oral
      antihyperglycemic drugs: a noninferiority intensification substudy of the DURABLE
      trial.
AB  - BACKGROUND: Insulin glargine and lispro mix 75/25 (75% insulin lispro protamine
      suspension and 25% insulin lispro injection [LM75/25]) represent 2 common starter
      insulin regimen classes: basal and premixed. After initiation of starter insulin
      therapy, if patients with type 2 diabetes mellitus (DM) are unable to achieve a
      glycosylated hemoglobin (HbA1c) level <7.0%, insulin intensification may be
      indicated. The DURABLE (Assessing Durability of Basal Versus Lispro Mix 75/25
      Insulin Efficacy) trial was designed to compare initiating insulin therapy with
      analogue basal insulin versus premixed analogue insulin in patients unable to
      achieve good glycemic control while taking multiple oral antihyperglycemic drugs
      (OADs). OBJECTIVE: To provide objective information about insulin
      intensification, the DURABLE trial also included a substudy evaluating a
      systematic approach to advancing insulin therapy in those patients who did not
      achieve glycemic control with their initial insulin regimen. This substudy, the
      results of which are reported here, tested the hypothesis that advancing insulin
      therapy with premixed insulin is noninferior to basal-bolus therapy (BBT) in
      patients with type 2 DM unable to achieve an HbA1c level < or = 7.0% after 6
      months of starter insulin therapy. METHODS: In the main DURABLE study, 2091
      patients (age range, 30-80 years) with type 2 DM and HbA1c values >7.0% receiving
      > or = 2 OADs were randomized to receive insulin glargine (n = 1046) or LM75/25
      (n = 1045), both in combination with prestudy OADs. After 6 months, patients with
      HbA1c levels >7.0% could enter this intensification substudy; OADs except
      sulfonylureas were continued. Patients originally receiving insulin glargine were
      enrolled in intensification arm A and were randomized to receive BBT (insulin
      glargine once daily plus mealtime insulin lispro TID) or LM75/25 BID. Patients
      originally receiving LM75/25 were enrolled in intensification arm B and
      randomized to receive BBT or mealtime 50% insulin lispro protamine suspension and
      50% insulin lispro injection (LM50/50) TID. Insulin doses were adjusted based on
      preprandial plasma glucose levels. The primary end point was noninferiority of
      premixed therapy versus BBT with respect to end-point HbA1c. Secondary end points
      included change in HbA1c and weight, percentage of patients reaching HbA1c target
      levels, total daily insulin dose, and rates of hypoglycemia. The safety profile
      was also assessed. RESULTS: Of the 475 patients in the insulin glargine + OAD arm
      of the main study who had HbA1c levels >7.0% at 6 months, 399 (84%) entered
      intensification arm A. The mean age was 57 years, 53% of the patients were male,
      and mean (SD) HbA1c was 8.0% (1.0%) at baseline. Of those patients, 199 were
      randomly assigned to receive BBT and 200 were assigned to receive LM75/25. Of the
      411 patients in the LM75/25 + OAD arm of the main study who had an HbA1c level
      >7.0% at 6 months, 345 (84%) entered intensification arm B. The mean age was 55
      years, 51% of the patients were male, and mean (SD) HbA1c was 8.0% (0.9%) at
      baseline. Of those patients, 171 were randomly assigned to receive BBT and 174
      were assigned to receive LM50/50. At end point, noninferiority of LM75/25 or
      LM50/50 to BBT was supported, with a 95% CI of -0.10 to 0.37 and -0.25 to 0.25,
      respectively. At 6 months, HbA1c did not differ significantly from baseline in
      any group. Regardless of treatment group, <20% of patients achieved an HbA1c
      level <7.0%. There were no significant differences between groups in total daily
      insulin dose, weight gain, incidence or rate of hypoglycemia, or incidence of
      serious adverse events. CONCLUSIONS: No group had significant improvement from
      baseline in HbA1c. Our study results suggest that premixed therapy, dosed 2 times
      per day (LM75/25) or 3 times per day (LM50/50), was noninferior to BBT (4
      injections/d) in this population of adult patients with type 2 DM previously
      uncontrolled with OADs plus basal insulin or twice-daily premixed insulin.
      Clinical-Trials.gov identifier: NCT00279201.

PMID- 20685498
TI  - Concomitant administration of simvastatin and danazol associated with fatal
      rhabdomyolysis.
AB  - BACKGROUND: Simvastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A reductase
      inhibitor, is indicated for the treatment of hypercholesterolemia and plays an
      important role in both the primary and secondary prevention of cardiovascular
      disease. Danazol is a steroid analogue approved for the treatment of
      endometriosis, fibrocystic breast disease, and hereditary angioedema. Despite not
      being licensed, danazol has been used for other off-label indications, such as
      idiopathic thrombocytopenic purpura (ITP), paroxysmal nocturnal hemoglobinuria,
      and aplastic anemia. OBJECTIVE: We report a case of fatal rhabdomyolysis that
      occurred after concomitant administration of simvastatin and danazol in a patient
      with ITP. CASE SUMMARY: An 80-year-old white male (height, 182 cm; weight, 90 kg)
      presented to the emergency department of the Clinical Hospital Centre Zemun,
      Belgrade, Serbia, with head injuries after an accidental fall caused by
      generalized weakness. He denied other complaints, except fatigue, mild pretibial
      edema, and progressive bilateral leg pain and cramping that began 7 days before.
      At the time of presentation, he was receiving aspirin 100 mg/d, clopidogrel 75
      mg/d, ramipril 2.5 mg/d, pantoprazole 40 mg/d, danazol 600 mg/d, prednisone 60
      mg/d, simvastatin 40 mg/d, and long-acting insulin 24 IU/d. After the injuries
      were treated, he was diagnosed with collapse and nasal contusion, and discharged
      without any changes in his therapy. Two days after initial presentation, the
      patient was readmitted to the hospital due to nausea, dark urine, and oliguria.
      All clinical signs (oliguria, dark urine, muscle pain, and tenderness) and
      laboratory markers (creatine kinase levels approximately 100 times the upper
      limit of normal, along with hyperkalemia, hyperphosphatemia, and hypoalbuminemia)
      were consistent with severe rhabdomyolysis. Despite intravenous hydration, forced
      diuresis, and hemodialysis, oliguria persisted and the patient died 6 days after
      admission. A score of 5 on the Naranjo adverse drug reaction probability scale
      was consistent with a probable association of rhabdomyolysis and concomitant
      treatment with simvastatin and danazol in this patient. CONCLUSIONS: Statin
      induced rhabdomyolysis must be considered whenever muscle or motor symptoms
      occur, especially when concomitant treatment with known inhibitors of statin
      metabolism is administered. Patients must be strictly monitored and the statin
      should be promptly discontinued with the onset of first signs and symptoms of
      myopathy. Clinicians should be aware of the potentially fatal consequences of
      both approved and unapproved treatments and be alert for the early detection of
      toxicity.

PMID- 20685499
TI  - Retrospective case series of three patients with plasma cell leukemia treated
      with bortezomib-based regimens.
AB  - BACKGROUND: Data from the literature have suggested that bortezomib is the only
      effective agent in the treatment of plasma cell leukemia (PCL), a type of plasma
      cell dyscrasia characterized by poor prognosis despite conventional chemotherapy
      including autologous and allogeneic transplantation. OBJECTIVE: This case series
      examined the antineoplastic activity of the bortezomib-based regimens in a small
      cohort of patients with PCL. CASE SUMMARIES: We describe a retrospective review
      of the 3 cases of PCL diagnosed at Antonio Perrino Hospital, Brindisi, Italy,
      between July 2004 and October 2006 (2 women and 1 man, all white, ages 71, 64,
      and 42 years; 2 with primary PCL and 1 with secondary PCL). These patients were
      treated with bortezomib variously combined with other drugs outside of clinical
      trials. Patients 1 and 2 received bortezomib-based regimens (bortezomib 1.3 mg/m2
      i.v. once daily on days 1, 4, 8, and 11; dexamethasone 20 mg i.v. once daily on
      days 1-4 and 8-11; oral cyclophosphamide 50 mg once daily on days 1-21, every 28
      days) after 2 previous chemotherapeutic treatments. Patient 3 received a
      bortezomib-based regimen (bortezomib 1.3 mg/m2 i.v. once daily on days 1, 4, 8,
      and 11; doxorubicin 9 mg/m2 i.v. once daily on days 1-4; and dexamethasone 40 mg
      i.v. once daily on days 1-4, 8-11, and 15-18 during cycle 1 and days 1-4 during
      subsequent cycles) after one previous chemotherapeutic regimen. In all 3
      patients, circulating plasma cells persisted. Patients 1 and 2 were not
      considered candidates for autologous peripheral blood stem cell transplantation
      (PBSCT) because of their nonresponse to the bortezomib-based regimens and severe
      deterioration of their clinical conditions (kidney and liver failure) due to
      disease progression. The overall survivals after administration of the bortezomib
      based regimens were 4 months in patient 1 and 1 month in patient 2. After
      further treatment according to the modified protocol for patients with acute
      lymphatic leukemia (cyclophosphamide 800 mg/m2 i.v. on day 1 and 200 mg/m2 i.v.
      on days 2-5; vincristine 1.5 mg/m2 i.v. once daily on days 1, 8, and 15;
      doxorubicin 40 mg/m2 i.v. on day 1; methotrexate 1200 mg/m2/h i.v. + 240 mg/m2/h
      i.v. for 23 hours [modified CODOX-M protocol]) due to the unavailability of a
      human leukocyte antigen-identical donor, patient 3 received high-dose (200 mg/m2)
      melphalan with autologous PBSCT, obtaining partial remission lasting 9 months.
      The patient died 5 months later because of disease progression. CONCLUSION: These
      3 patients with primary or secondary PCL who received a bortezomib-based regimen
      as rescue medication did not respond to treatment.

PMID- 20685500
TI  - Antipsychotic use in children, adolescents, and pregnant women--the critical need
      for information.

PMID- 20685501
TI  - Effects of the pharmaceutical technologic aspects of oral pediatric drugs on
      patient-related outcomes: a systematic literature review.
AB  - BACKGROUND: In view of the high rates of off-label and unlicensed prescribing of
      drugs in children, the US Food and Drug Administration and the European Union
      have implemented legislative regulations for the pharmaceutical industry to
      increase the number of drugs with approved pediatric labeling. However, the
      extent to which the effects of pharmaceutical technologic aspects of pediatric
      oral drugs (eg, taste, route and frequency of administration, user instructions)
      on patient-related outcomes (eg, efficacy, tolerability, preference, adherence)
      can be based on clinical evidence from the available literature is unknown.
      OBJECTIVE: This systematic literature review aimed to identify the nature,
      volume, and quality of comparative studies that have assessed the effects of
      pharmaceutical technologic aspects of oral pediatric drugs on patient-related
      outcomes. METHODS: The Cochrane, EMBASE, and MEDLINE databases were searched from
      their start through December 31, 2009. Studies were eligible for inclusion if
      they were published in English; included search terms for child, study design,
      medicine, formulation aspects, dosage form, routes of administration, patient
      acceptance, adherence, side effects and tolerability, and/or efficacy; reported
      on > or = 10 children aged 0 to <18 years; and described the effects of > or = 1
      of 3 pharmaceutical technologic aspects of an oral pediatric drug (formulation
      and dosage form; route and frequency of administration; and/or packaging,
      administration device, and user instruction) on > or = 1 of 6 patient-related
      outcomes (clinical efficacy, side effects and tolerability, patient preference,
      patient acceptance, administration errors, and/or adherence). Studies were
      excluded if they concerned a nonallopathic drug (ie, homeopathic remedy,
      anthroposophic drug, herbal supplement, or food supplement); related to asthma
      (because modern asthma treatment protocols strongly favor the use of drug
      inhalation above oral medication); and/or related to analgesics. The
      characteristics of each of the included publications were assessed with respect
      to pharmaceutical technologic aspect studied; patient-related outcomes studied;
      pharmacotherapeutic indication; year of publication; geographic location; number
      and age of the included subjects; and sponsorship by industry and/or author
      affiliation with the pharmaceutical industry. The electronic search was
      supplemented with a manual search of the cited references. RESULTS: Ninety-four
      publications were identified as eligible for inclusion. These publications
      reported on 176 assessments of the effects of > or = 1 pharmaceutical technologic
      aspect on > or = 1 patient-related outcome. Fifty-five percent of the studies
      were conducted in children aged 2 or 3 years, and 69% in children aged 4 or 5
      years. Forty-three percent of the publications included > or = 100 patients.
      Fifty-one percent of the studies were conducted in the United States or Canada,
      and 29% in Europe. Antibacterials for systemic use were the subject of 30% of the
      included publications. Two of the 94 publications were of appropriate
      methodologic quality (Jadad score > or = 4). Forty-nine percent of the studies
      were sponsored by the pharmaceutical industry or were written by > or = 1 author
      affiliated with the industry. Sixty-eight percent of the included studies had
      Jadad scores of 0 or 1 (poor quality). The proportion of industry-sponsored or
      industry-authored studies with a Jadad score > or = 2 or in > or = 100 children
      was not significantly different from that of non-industry-sponsored or-authored
      studies. The proportion of industry-sponsored or industry-authored studies
      conducted in the United States/Canada (48 [51%]) was not significantly different
      from that of studies conducted elsewhere (46 [49%]). The distribution of
      technologic aspects assessed in the included studies were formulation and dosage
      form, 48%; route and frequency of administration, 44%; and packaging,
      administration device, and user instruction, 8%. Seventy-six assessments included
      > or = 100 patients. Twenty-one of these assessments addressed patient acceptance
      or patient preference; 17, clinical efficacy; and 14, side effects and
      tolerability. CONCLUSIONS: This systematic review identified 94 articles on oral
      drugs for use in children and adolescents, which reported on a total 176
      assessments of the effects of 3 pharmaceutical technologic aspects (formulation
      and dosage form; route and frequency of administration; and packaging,
      administration device, and user instruction) on 6 patient-related outcomes
      (clinical efficacy, side effects and tolerability, patient preference, patient
      acceptance, administration errors, and adherence). Only 2 of the 94 publications
      were of appropriate methodologic quality. These results suggest that published
      clinical evidence to support pharmaceutical development programs is limited.

PMID- 20685502
TI  - Efficacy of inhaled nitric oxide for hypoxic respiratory failure in term and late
      preterm infants by baseline severity of illness: a pooled analysis of three
      clinical trials.
AB  - BACKGROUND: The use of inhaled nitric oxide (NO) has been studied for the
      treatment of hypoxic respiratory failure (HRF) in newborns who require mechanical
      ventilation. Although inhaled NO is typically used in patients with a greater
      severity of illness, the treatment response (eg, improvement in oxygenation) and
      the associated outcomes (eg, time on mechanical ventilation) may be affected by
      the timing of treatment and baseline severity of illness. OBJECTIVES: This
      analysis was conducted to assess the effects of inhaled NO on measures of
      oxygenation, efficacy of inhaled NO across a range of illness severity strata,
      and duration of mechanical ventilation. METHODS: This was a retrospective pooled
      analysis of 3 pivotal clinical trials comparing inhaled NO (starting dose, 20
      ppm) with control (100% oxygen or nitrogen gas) in term and late preterm
      (gestational age > or = 34 weeks) infants with HRF who required mechanical
      ventilation. Data on partial pressure of arterial oxygen (PaO2), inspired oxygen
      concentration, and mean airway pressure at 0 and 30 minutes after administration
      of inhaled NO were extracted from the case-report forms from the 3 clinical
      trials and used to calculate the oxygenation index (OI). The change in PaO2 was
      assessed by baseline severity of illness, stratified based on the OI (< or = 15 =
      mild, >15 to < or = 25 = moderate, >25 to < or = 40 = severe, >40 = very severe).
      The duration of mechanical ventilation was compared between the inhaled NO and
      control groups. RESULTS: Five hundred twenty-four patients were analyzed (260
      inhaled NO, 264 control). The overall mean (SD) birth weight and gestational age
      of the patients were 3.4 (0.58) kg and 39.1 (1.96) weeks, respectively. After 30
      minutes of treatment, there was a significant increase from baseline in PaO2 with
      inhaled NO compared with control (54.91 vs 14.15 mm Hg, respectively; P < 0.001).
      The increases from baseline in PaO2 at 30 minutes were statistically significant
      for inhaled NO compared with controls across all severity strata (mild: 62.39 vs 
      23.03 mm Hg, respectively [P = 0.003]; moderate: 52.93 vs 18.28 mm Hg [P =
      0.004]; severe: 62.07 vs 13.95 mm Hg [P < 0.001]; very severe: 45.17 vs 18.66 mm
      Hg [P < 0.001]). On Kaplan-Meier analysis, the median duration of mechanical
      ventilation was 11 and 14 days in the inhaled NO and control groups, respectively
      (P = 0.003). CONCLUSIONS: This pooled analysis of data from 3 clinical trials in
      term and late preterm infants with HRF requiring mechanical ventilation found
      that inhaled NO at a starting dose of 20 ppm was associated with improved
      oxygenation acutely and a reduced median duration of mechanical ventilation. The
      improvements were significant across all severity-of-illness strata.

PMID- 20685503
TI  - Antipsychotic polypharmacy in the treatment of children and adolescents in the
      fee-for-service component of a large state Medicaid program.
AB  - OBJECTIVES: The aims of this study were to quantify and describe antipsychotic
      polypharmacy use among patients aged 6 to 12 years (children) and 13 to 17 years
      (adolescents) and to identify the characteristics of polypharmacy recipients.
      METHODS: Data from patients enrolled in Florida's Medicaid fee-for-service
      program and receiving treatment with an antipsychotic were included.
      Antipsychotic polypharmacy was defined as the receipt of > or = 2 antipsychotic
      medications concurrently for >60 days, with no gaps >15 days in polypharmacy
      treatment. The prevalence of antipsychotic polypharmacy, durations of treatment
      episodes, times to antipsychotic polypharmacy after initiation of antipsychotic
      monotherapy, and rates of antipsychotic combination use were calculated for the
      period between July 2002 and June 2007. RESULTS: During the 5-year period, 12,764
      children and 10,419 adolescents received antipsychotic treatment. The proportions
      of patients who were male (73% and 63%) and whose race was indicated as "other"
      (31% and 14%) were significantly greater in children than in adolescents,
      respectively (both, P < 0.001). Seven percent of the children and 8% of the
      adolescents were prescribed antipsychotic polypharmacy (P = 0.001). Mean (SD)
      durations of polypharmacy episodes were 170.0 (139.0) days in children and 185.5
      (175.9) days in adolescents (P = 0.010). Times to initiation of polypharmacy were
      505.8 (440.5) days in children and 384.9 (424.3) days in adolescents (P < 0.001).
      Adolescents (odds ratio [OR] = 1.16; 95% CI, 1.04-1.29) were more likely than
      children to be polypharmacy recipients, as were those with psychotic disorders
      (OR = 1.47; 95% CI, 1.20-1.81) compared with those with bipolar I disorder.
      Patients whose race was indicated as "other" were more likely than patients of
      white race to receive polypharmacy (OR = 1.18; 95% CI, 1.04-1.34; P < 0.001);
      other ethnic/racial groups did not differ significantly. The most common specific
      antipsychotic combinations prescribed in children and adolescents were
      aripiprazole/quetiapine (23% and 17%, respectively), risperidone/quetiapine (18%
      and 15%), aripiprazole/risperidone (17% and 11%), risperidone/olanzapine (5% and
      6%), and quetiapine/olanzapine (4% and 7%). CONCLUSIONS: The prevalence and
      duration of Antipsychotic polypharmacy among antipsychotic recipients in this
      Medicaid fee-for-service population were noteworthy. Research on the risks and
      benefits of the practice in the pediatric population is needed.

PMID- 20685504
TI  - Patient-centered services: what could we be doing right?

PMID- 20685505
TI  - Impact of prior authorization for asthma medications on the use of emergency
      health services: a retrospective cohort study among newly diagnosed patients with
      asthma.
AB  - BACKGROUND: A prior authorization process to limit the nonoptimal use of
      medications combining inhaled corticosteroids and long-acting bronchodilators was
      introduced in the province of Quebec, Canada, on October 1, 2003. OBJECTIVE: We
      assessed the impact of this administrative measure on the rate of asthma-related
      emergency department (ED) visits and hospitalizations. METHODS: A retrospective
      cohort study was conducted using Regie de l'assurance maladie du Quebec
      administrative databases. We identified all persons aged 6 to 44 years with an
      incident asthma diagnosis in the 2-year periods preceding (October 1, 2001
      September 30, 2003) and following (October 1, 2003-September 30, 2005) the
      introduction of the process. Children aged < or = 5 years at the time of the
      first encountered diagnosis were excluded because it is difficult to make an
      objective asthma diagnosis until 6 years of age. People aged > or = 45 years at
      the time of the first encountered diagnosis were also excluded to avoid the
      inclusion of persons who might also have had chronic obstructive pulmonary
      disease. Two groups were created based on their prescription drug insurance
      (private or public). Publicly insured persons were considered exposed to the
      process while privately insured persons were considered not exposed. Cox
      proportional hazards regression was used to assess, for each insurance group, the
      hazard ratio (HR) for an asthma-related first hospitalization or ED visit between
      the 2 periods. The use of medication, quality of life, and visits to physicians'
      offices were not considered in the analysis. The interaction between group and
      period was assessed to test whether the change in risk between the preprocess and
      postprocess periods differed by insurance group; statistical models were adjusted
      for sex, age, region, presence of a comorbidity other than asthma, and discipline
      of diagnosing physician. RESULTS: There were 47,579 publicly insured persons and
      93,177 privately insured persons with incident asthma during the study period.
      The risk of an asthma-related first hospitalization or ED visit remained
      unchanged in the 2 periods evaluated among both the publicly insured (adjusted
      HR, 0.95 [95% CI, 0.88-1.03]) and the privately insured (adjusted HR, 1.03 [95%
      CI, 0.96-1.03]). The change in risk between the preprocess and postprocess
      periods was not significantly different between insurance groups. CONCLUSIONS:
      The prior authorization process introduced to limit the nonoptimal use of
      combination products (formoterol/budesonide and salmeterol/fluticasone) had no
      apparent impact on first asthma-related hospitalization or ED visit in these
      patients newly diagnosed with asthma who were covered by Quebec's public
      prescription drug insurance plan.

PMID- 20685506
TI  - The status of glycemic control: A cross-sectional study of outpatients with type
      2 diabetes mellitus across primary, secondary, and tertiary hospitals in the
      Jiangsu province of China.
AB  - OBJECTIVES: The aims of the study were to determine the following: the status of
      glycemic control in patients with type 2 diabetes mellitus (DM) at primary,
      secondary, and tertiary hospitals in the Jiangsu province of China; and the
      factors associated with achieving glycemic targets. METHODS: This study, in which
      patients were enrolled from July 20 to 31, 2009, at 56 diabetes centers, used a
      multiple-stage, stratified sampling method to select a representative sample of
      the population with DM in Jiangsu. The sampling process was stratified by
      geographic and demographic regions, and by the outpatient numbers in the
      hospitals. A primary hospital was defined as a community medical institution that
      provided primary health services; a secondary hospital was a local medical
      institution that provided comprehensive health services; and a tertiary hospital
      was a regional medical institution that provided comprehensive and specialist
      health services. In primary hospitals, patients with DM were treated by general
      physicians; at secondary and tertiary hospitals, they were seen by specialists.
      Also, primary and tertiary hospitals treated patients in cities, whereas
      secondary hospitals treated patients from towns or rural areas. Patients with a
      medical history of type 2 DM for >6 months and registration at each diabetes
      center for > or = 6 months, and who were residents of Jiangsu province, were
      recruited. During the patient enrollment visit, information about DM
      complications and comorbidities, as well as DM management, was obtained by
      retrospectively reviewing medical records; basic patient data (eg, date of birth,
      sex, weight, height) were obtained by patient interview. Blood samples were
      collected for assessment of glycosylated hemoglobin (HbA1c) at a central
      laboratory. RESULTS: Of 3046 sampled subjects, the analysis was performed in 2966
      subjects with complete data. The mean (SD) HbA1c value for analyzed patients was
      7.2% (1.6%). The proportion of patients with tight glycemic control was 40.2%
      (1193/2966) when a threshold of HbA1c <6.5% was used, and 56.1% (1665/2966) when
      a threshold of HbA1c <7.0% was used. Compared with patients who had inadequate
      glycemic control, those with tight control were younger (P < 0.001), had shorter
      duration of DM (P < 0.001), had lower body mass index (BMI) (P = 0.005 for HbA1c
      <6.5% and P = 0.01 for HbA1c <7.0%), had more education (P < 0.001) and income (P
      = 0.003 for HbA1c <6.5% and P = 0.008 for HbA1c <7.0%), were more likely to
      monitor their glucose (P = NS for HbA1c <6.5% and P = 0.043 for HbA1c <7.0%) and
      attend DM education (P = 0.027 for HbA1c <6.5% and P = 0.002 for HbA1c <7.0%) at
      least once a month, and were more likely to receive oral antidiabetic drugs
      (OADs) (P < 0.001). Age, BMI, and DM duration did not differ significantly
      between hospital types. Compared with primary (36.2%) and secondary hospitals
      (36.5%), tertiary hospitals (42.2%) had more patients with HbA1c <6.5% (P =
      0.043); tertiary hospitals also had more patients with once-monthly glucose self
      monitoring (P = 0.001), patients with higher income (P < 0.001) and education (P
      < 0.001), and those who were more likely to use > or = 2 OADs or insulin with
      OADs (P < 0.001). CONCLUSION: The overall status of glycemic control was
      unsatisfactory during the study period, although patients at tertiary hospitals
      appeared to have better control than those at primary or secondary hospitals.

PMID- 20685507
TI  - Bioequivalence and pharmacokinetic evaluation of two formulations of glimepiride
      2 mg: a single-dose, randomized-sequence, open-label, two-way crossover study in
      healthy Chinese male volunteers.
AB  - BACKGROUND: Glimepiride is an oral sulfonylurea antihyperglycemic agent indicated
      for the treatment of type 2 diabetes mellitus. Although there are reports in the
      literature regarding the pharmacokinetic (PK) characteristics of glimepiride, few
      data of PK parameters are available in a Chinese population; none are available
      regarding a recently developed generic formulation. OBJECTIVE: To meet the
      requirements for marketing a new generic product in China, the study was designed
      to compare the PK properties and bioequivalence of 2-mg tablets of glimepiride:
      the newly developed generic formulation (test) and a branded formulation
      (reference) in healthy Chinese male volunteers. METHODS: A single-dose,
      randomized-sequence, open-label, 2-way crossover study was conducted in fasted
      healthy Chinese male volunteers. Eligible participants were randomly assigned in
      a 1:1 ratio to receive 1 tablet (2 mg each) of the test or reference formulation,
      followed by a 1-week washout period and administration of the alternate
      formulation. The study drugs were administered after a 10-hour overnight fast.
      Plasma samples were collected before study drug administration (baseline) and at
      0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, and 48 hours after study drug
      administration. Concentrations in plasma of the parent glimepiride and its M1
      metabolite were analyzed with a LC-MS/MS method. The formulations were considered
      bioequivalent if the 90% CIs for the log-transformed values were within the
      predetermined equivalence range (70%-143% for C(max) and 80%-125% for AUC),
      according to the guidelines of the State Food and Drug Administration (SFDA) of
      China. Tolerability was based on the recording of adverse events (AEs),
      monitoring vital signs, ECGs, and laboratory tests at baseline and completion of
      the study. RESULTS: A total of 24 healthy Chinese male volunteers were enrolled
      and completed the study; however, only the data from 23 subjects were included
      (mean [SD] age, 23.6 [2.2] years [range, 18.6-26.9 years]; weight, 64.0 [8.4] kg
      [range, 52.0-82.0 kg]; and height, 172.3 [5.6] cm [range, 164.0-185.0 cm) in the
      PK and tolerability assessments due to a violation of the protocol. For parent
      glimepiride, the 90% CIs for the ratios of Cmax, AUC(0-t), and AUC(0-infinity)
      were 93.83% to 115.19%, 90.82% to 102.29%, and 92.22% to 103.78%, respectively.
      For the M1 metabolite, the 90% CIs were 91.71% to 110.79%, 91.33% to 101.76%, and
      89.99% to 99.85%. Both met the predetermined criteria for bioequivalence. Four
      AEs (17.4%) were reported: hypertriglyceridemia (2 subjects [8.7%]; 1 each
      receiving the test and reference formulations); increase of red blood cells in
      urine (1 subject [4.3%] receiving the reference formulation); and hypoglycemia (1
      subject [4.3%] receiving the test formulation). The incidence of hypoglycemia was
      the only AE considered probably related to study drug administration; all others
      were considered probably not related. All AEs were transient and considered by
      the investigators to be mild. CONCLUSIONS: In this small study in fasted healthy
      Chinese male volunteers, a single 2-mg dose of the test formulation met the
      regulatory criteria to assume bioequivalence to the reference formulation based
      on the rate and extent of absorption. Both formulations were well tolerated. SFDA
      Registration No.: 2009L01033.

PMID- 20685508
TI  - The article by Daley-Yates et al.

PMID- 20685512
TI  - The center and axis of tooth movement.

PMID- 20685513
TI  - Root resorption.

PMID- 20685517
TI  - Systematic review of self-ligating brackets.
AB  - INTRODUCTION: Self-ligating brackets have been gaining popularity over the past
      several decades. Various advantages for these systems have been claimed. The
      purposes of this systematic review were to identify and review the orthodontic
      literature with regard to the efficiency, effectiveness, and stability of
      treatment with self-ligating brackets compared with conventional brackets.
      METHODS: An electronic search in 4 data bases was performed from 1966 to 2009,
      with supplemental hand searching of the references of retrieved articles. Quality
      assessment of the included articles was performed. Data were extracted by using
      custom forms, and weighted mean differences were calculated. RESULTS: Sixteen
      studies met the inclusion criteria, including 2 randomized controlled trials with
      low risk of bias, 10 cohort studies with moderate risk of bias, and 4 cross
      sectional studies with moderate to high risk of bias. Self-ligation appears to
      have a significant advantage with regard to chair time, based on several cross
      sectional studies. Analyses also showed a small, but statistically significant,
      difference in mandibular incisor proclination (1.5 degrees less in self-ligating
      systems). No other differences in treatment time and occlusal characteristics
      after treatment were found between the 2 systems. No studies on long-term
      stability of treatment were identified. CONCLUSIONS: Despite claims about the
      advantages of self-ligating brackets, evidence is generally lacking. Shortened
      chair time and slightly less incisor proclination appear to be the only
      significant advantages of self-ligating systems over conventional systems that
      are supported by the current evidence.

PMID- 20685519
TI  - Accuracy of surgical positioning of orthodontic miniscrews with a computer-aided
      design and manufacturing template.
AB  - INTRODUCTION: Our objective was to enable accurate miniscrew placement after
      preoperative simulation. We developed a new template for miniscrew placement and
      evaluated its accuracy. METHODS: Eleven patients who had bimaxillary protrusion
      were scanned with computed tomography. The 3-dimensional computed tomography data
      were used to produce, with stereolithography apparatus, a template for accurate
      miniscrew placement. The interradicular space available for miniscrew placement
      was calculated in the 3-dimensional images. Postoperative computed tomography
      images were matched with preoperative images to calculate the deviations between
      the planned and actual placements. RESULTS: The distance for placement of a
      miniscrew between 2 roots was 4.12 mm (SD, 0.25 mm; range, 3.7-4.5 mm). The
      placed miniscrews showed an average angular deviation of 1.2 degrees (SD, 0.43
      degrees ; range, 0.6 degrees -2.41 degrees ) compared with the plan, whereas the
      mean linear distomesial deviation was 0.42 mm (SD, 0.13 mm; range, 0.15-0.6 mm)
      at the tip. CONCLUSIONS: The proposed template has high accuracy and will be
      especially useful for patients who require precise miniscrew placement.

PMID- 20685521
TI  - Tooth-wear patterns in adolescents with normal occlusion and Class II Division 2
      malocclusion.
AB  - INTRODUCTION: In this study, we investigated tooth-wear patterns in adolescents
      with either normal occlusion or Class II Division 2 malocclusion. METHODS: The
      sample consisted of dental casts from 165 subjects that were divided into 2
      groups: 115 normal occlusion subjects (mean age, 14.3 years) and 50 complete
      Class II Division 2 subjects (mean age, 13.9 years). Dental wear was assessed by
      using a modified version of the tooth wear index. The 2 groups were compared with
      the Mann-Whitney test for the frequency and severity of wear on each surface of
      each group of teeth. The level of statistical significance was set at 5%.
      RESULTS: The normal occlusion group statistically had greater tooth wear on the
      incisal surfaces of the maxillary lateral incisors and the incisal surfaces of
      the maxillary canines than did the Class II Division 2 malocclusion group. The
      malocclusion group showed statistically greater tooth wear on the labial surfaces
      of the mandibular lateral incisors, the occlusal surfaces of the maxillary
      premolars and first molars, the occlusal surfaces of the mandibular premolars,
      the palatal surfaces of the maxillary second premolars, and the buccal surfaces
      of the mandibular premolars and first molars than did the normal occlusion group.
      CONCLUSIONS: Subjects with normal occlusion and those with complete Class II
      Division 2 malocclusions have different tooth-wear patterns. Tooth wear on the
      malocclusion subjects should not be considered pathologic but, rather, the
      consequence of different interocclusal arrangements.

PMID- 20685523
TI  - Agenesis of maxillary lateral incisors and associated dental anomalies.
AB  - INTRODUCTION: The objectives of this study were to evaluate the prevalence of
      dental anomalies in patients with agenesis of maxillary lateral incisors and to
      compare the findings with the prevalence of these anomalies in the general
      population. METHODS: A sample of 126 patients, aged 7 to 35 years, with agenesis
      of at least 1 maxillary lateral incisor was selected. Panoramic and periapical
      radiographs and dental casts were used to analyze other associated dental
      anomalies, including agenesis of other permanent teeth, ectopia of unerupted
      permanent teeth, microdontia of maxillary lateral incisors, and supernumerary
      teeth. The occurrence of these anomalies was compared with prevalence data
      previously reported for the general population. Statistical testing was performed
      with the chi-square test (P <0.05) and the odds ratio. RESULTS: Patients with
      maxillary lateral incisor agenesis had a significantly increased prevalence rate
      of permanent tooth agenesis (18.2%), excluding the third molars. The occurrence
      of third-molar agenesis in a subgroup aged 14 years or older (n = 76) was 35.5%.
      The frequencies of maxillary second premolar agenesis (10.3%), mandibular second
      premolar agenesis (7.9%), microdontia of maxillary lateral incisors (38.8%), and
      distoangulation of mandibular second premolars (3.9%) were significantly
      increased in our sample compared with the general population. In a subgroup of
      patients aged 10 years or older (n = 115), the prevalence of palatally displaced
      canines was elevated (5.2%). The prevalences of mesioangulation of mandibular
      second molars and supernumerary teeth were not higher in the sample. CONCLUSIONS:
      Permanent tooth agenesis, maxillary lateral incisor microdontia, palatally
      displaced canines, and distoangulation of mandibular second premolars are
      frequently associated with maxillary lateral incisor agenesis, providing
      additional evidence of a genetic interrelationship in the causes of these dental
      anomalies.

PMID- 20685525
TI  - Arch-width and perimeter changes in patients with borderline Class I malocclusion
      treated with extractions or without extractions with air-rotor stripping.
AB  - INTRODUCTION: The aim of this study was to compare dental arch-width and
      perimeter changes in patients with borderline Class I occlusion, treated with
      extractions or without extractions with air-rotor stripping (ARS). METHODS: The
      study was conducted with 26 sets of pretreatment and posttreatment dental models
      of patients with borderline Class I occlusion. Thirteen patients (mean age, 18.1
      +/- 3.7 years) were treated with 4 premolar extractions, and 13 (mean age, 17.8
      +/- 2.4 years) were treated without extractions but with the ARS technique. Mean
      maxillary and mandibular crowding values were 5.7 +/- 1.5 and 5.9 +/- 1.4 mm in
      the extraction group, and 5.0 +/- 1.3 and 5.9 +/- 1.3 mm in the nonextraction
      group, respectively. A digital caliper was used to measure maxillary and
      mandibular intercanine and intermolar arch widths and arch perimeters. The
      Wilcoxon test was used to evaluate treatment changes in each group. The Mann
      Whitney U test was used to compare the pretreatment and posttreatment values and
      the treatment changes between the 2 groups. RESULTS: At the start of treatment,
      the maxillary and mandibular intercanine and intermolar widths and the arch
      perimeters of both groups did not differ statistically. The maxillary intercanine
      widths were maintained in both groups. The maxillary and mandibular intermolar
      widths and arch perimeters decreased in the extraction group. In the
      nonextraction group, intermolar widths decreased, but arch perimeters did not
      change significantly. After treatment, the maxillary and mandibular intercanine
      widths were not different between the groups. CONCLUSIONS: In Class I borderline
      patients with moderate crowding, extraction therapy with minimum anchorage did
      not result in narrower dental arches, and nonextraction treatment with ARS
      preserved the intercanine arch widths and arch perimeters.

PMID- 20685527
TI  - Longitudinal study of relative growth rates of the maxilla and the mandible
      according to quantitative cervical vertebral maturation.
AB  - INTRODUCTION: The purpose of this study was to investigate the relative growth
      rates (RGR) of the maxilla and the mandible according to quantitative cervical
      vertebral maturation (QCVM) of adolescents with normal occlusion. METHODS: Mixed
      longitudinal data were used. The sample included 87 adolescents (32 boys, 55
      girls) from 8 to 18 years of age with normal occlusion, selected from 901
      candidates. Sequential lateral cephalograms and hand-wrist films were taken once
      a year for 6 consecutive years. The growth magnitude (GM) and RGR of the maxilla
      and the mandible were measured and analyzed. RESULTS: GM and RGR were not always
      consistent, because subjects had different periods of time between the QCVM
      stages. GM was not as reliable as RGR. RGR had no significant sex differences in
      the maxilla and the mandible, in spite of different decelerating curves. However,
      statistically significant sex differences were found in the GM of mandibular
      measurements. The greatest growth potentials were not synchronized between the
      maxilla and the mandible. For both sexes, the greatest RGR of maxillary length
      and height was in QCVM stage I; then, deceleration occurred. The greatest RGR of
      mandibular length and height was in QCVM stage II, and the next largest was in
      QCVM stage I. CONCLUSIONS: Understanding the RGR can provide references for
      orthodontic treatment and orthognathic surgery.

PMID- 20685528
TI  - Randomized clinical trial of orthodontic treatment efficiency with self-ligating
      and conventional fixed orthodontic appliances.
AB  - INTRODUCTION: Our objective was to test the hypotheses that treatment with 2
      fixed orthodontic appliances (SmartClip and Victory; 3M Unitek, Monrovia, Calif)
      would result in no difference in (1) the duration of orthodontic treatment or (2)
      the number of visits required. METHODS: Sixty-six consecutive patients were
      randomly allocated to treatment with a self-ligating bracket system (SmartClip)
      or a conventional appliance (Victory). The duration of treatment and the number
      of visits required in addition to the initial and final peer assessment rating
      (PAR) scores were recorded. The number of teeth extracted during treatment and
      the frequency of mechanical eruption of canines were also noted. Analyses of
      covariance were used to assess the influence of bracket type on treatment
      durations, visits required, and percentage PAR score reductions. RESULTS: Fifty
      four (81.8%) participants completed the study. The duration of treatment was 3
      months greater in the group treated with SmartClip. However, bracket type had no
      statistical influence on treatment duration (P = 0.076), total visits required (P
      = 0.184), or percentage PAR score reduction (P = 0.255). CONCLUSIONS: Neither
      hypothesis could be rejected. Bracket type did not influence the duration of
      treatment or the number of visits required. The percentages of PAR score
      reductions were also unaffected by the choice of appliance.

PMID- 20685529
TI  - Analysis of failure in the treatment of impacted maxillary canines.
AB  - INTRODUCTION: In this study, we aimed to evaluate the reasons for failure of
      orthodontic treatment for impacted maxillary canines and to recommend measures to
      overcome them. METHODS: Twenty-eight patients (ages, 17.4 +/- 4.3 years) with 37
      maxillary impacted canines were referred after a failed attempt to resolve the
      impaction. Reasons for failure were analyzed, and corrective measures undertaken.
      The success rate of the revised treatments and the durations of both treatments
      were recorded. RESULTS: The mean duration of the failed treatments was 26.2 +/-
      17.2 months. The failed treatments were mostly based on plane radiographs, intra
      arch dental anchorage, and elastic traction directly to the labial archwire. The
      major reasons for failure were inadequate anchorage (48.6%), mistaken location
      and directional traction (40.5%), and ankylosis (32.4%). In several patients,
      there was more than 1 possible reason for failure. The success rate of the
      revised treatments was 71.4%, and the mean duration was 14.4 +/- 7.2 months.
      Repeat surgery was needed for 62.9% of the canines in which corrective treatment
      was started, mostly to redirect the ligature wires. The corrective measures
      included the use of 3-dimensional imaging and a change in the direction of
      traction. Anchorage was reinforced by dental and skeletal means. CONCLUSIONS:
      Inaccurate 3-dimensional diagnosis of location and orientation of impacted teeth
      and failure to appreciate anchorage demands were the major reasons for failure in
      the treatment of impacted canines.

PMID- 20685530
TI  - Factors affecting the clinical approach to impacted maxillary canines: A Bayesian
      network analysis.
AB  - INTRODUCTION: The aim of this study was to apply Bayesian networks to evaluate
      the relative role and possible causal relationships among various factors
      affecting the diagnosis and final treatment outcome of impacted maxillary
      canines. METHODS: A total of 168 patients with infraosseous impacted maxillary
      canines had a combined surgical-orthodontic approach aimed to guide the impacted
      tooth to the center of the alveolar ridge. Demographic, orthodontic, and
      periodontal variables were recorded and analyzed by means of Bayesian network
      analysis. RESULTS: All 168 impacted canines were successfully moved and aligned
      in the dental arches with healthy periodontiums. According to the Bayesian
      network analysis, bilateral impaction was associated with palatal impaction and
      longer treatment; the pretreatment alpha-angle was a determinant for the duration
      of orthodontic traction, also because of the associations between greater
      angulation of impacted canines with more severe tooth displacement and with
      greater distance of the impacted canine from the occlusal plane; the
      posttreatment periodontal outcome was not related to the pretreatment
      radiographic variables. CONCLUSIONS: Bayesian network analysis was useful to
      identify possible relationships among the variables considered for diagnosis and
      treatment of impacted canines.

PMID- 20685531
TI  - Craniofacial morphology and adolescent facial growth in Pierre Robin sequence.
AB  - INTRODUCTION: The purpose of this research was to analyze craniofacial morphology
      and adolescent facial growth in subjects with Pierre Robin sequence (PRS). The
      research was conducted at the Center for Craniofacial Care and Research at The
      Hospital for Sick Children, Toronto, Ontario, Canada, and the Burlington Facial
      Growth Research Center, Faculty of Dentistry, University of Toronto. METHODS:
      Longitudinal lateral cephalometric tracings of 34 Caucasian subjects with
      nonsyndromic PRS were compared with those of unaffected control subjects, matched
      for age, sex, and ethnicity, and representing the range of occlusions in an
      untreated population. Cephalometric measurements were obtained before orthodontic
      treatment (age, 11.8 years) and after orthodontic treatment but before any
      surgical treatment (age, 16.6 years). Between-group differences of craniofacial
      measurements were analyzed with paired t-tests, and longitudinal growth
      differences were analyzed with analysis of variance (ANOVA) adjusted for the
      growth interval. RESULTS: Significant differences were noted, with the PRS group
      showing smaller cranial base length, shorter maxillary and mandibular lengths,
      increased palatal and mandibular plane inclinations, and more open mandibular
      flexure. Mandibular body length and height were smaller as were ramal length and
      width, anterior basal thickness, and chin thickness. The ramus-to-body ratio was
      greater. With growth, greater gains in anterior face and symphyseal height were
      seen, but the mandible showed less closure of its internal flexure. The maxilla
      and the mandible remained retrusive during adolescent growth, and the maxilla
      became more retrognathic. Mandibular morphologic differences persisted in spite
      of additionally adjusting for cranial base length in the analysis. CONCLUSIONS:
      Subjects with PRS had reduced cranial base and maxillary and mandibular lengths.
      Mandibular deficiency was most pronounced in the body. Due to bimaxillary
      retrognathism, the maxillomandibular dysplasia was not significant. A vertical
      growth pattern worsened the profile. There was no evidence of adolescent
      mandibular catch-up growth.

PMID- 20685532
TI  - Natural changes of the maxillary first molars in adolescents with skeletal Class
      II malocclusion.
AB  - INTRODUCTION: The objective of this study was to evaluate natural changes in
      maxillary posterior alveolar height (MPAH) and axial inclination of the maxillary
      first molars (AIMFM) in subjects with Class II malocclusion to determine the
      validity of predictive equations. METHODS: Longitudinal records of 30 untreated
      white subjects (13 girls, 17 boys) with skeletal Class II malocclusion were
      collected at ages 9, 12, 14, and 16 years. They had participated in the
      Burlington Growth Centre study, and cephalograms were analyzed with Dentofacial
      Planner Plus software (version 2.0, Dentofacial Planner, Toronto, Ontario,
      Canada). Serial means were compared with the Bonferroni post-hoc test (P <0.05).
      Predictive equations were obtained and studied with the analysis of agreement.
      RESULTS: Gradually, means of MPAH had statistical increments with sexual
      dimorphism from 14 to 16 years of age. A distal mean of AIMFM was found at 9
      years of age that decreased significantly during growth, with sexual dimorphism
      between the ages of 9 and 12 years. Changes in AIMFM varied among subjects in
      distinct stages. Values of MPAH were predicted with high validity at intervals of
      3 years or longer, whereas estimations for AIMFM were unreliable. CONCLUSIONS: In
      this study group, there was significant alveolar growth, with a natural tendency
      to upright the distal inclination at the maxillary first molars.

PMID- 20685533
TI  - Changes in nasal volume after surgically assisted bone-borne rapid maxillary
      expansion.
AB  - INTRODUCTION: The purposes of this study were to detect, locate, and examine the
      changes in transverse nasal width, area, and volume from bone-borne, surgically
      assisted rapid maxillary expansion (SARME) with the Dresden distractor by using
      computer tomography (CT). METHODS: Sixteen patients (average age, 28.7 years)
      underwent axial CT scanning before and 6 months after SARME. They also underwent
      CT fusion on specific bony structures. The nasal bone width was examined in the
      coronal plane. The cross-sectional images of the nasal cavity were taken of the
      area surrounding the apertura piriformis, the choanae, and in between. We
      calculated cross-sectional areas and nasal volume according to these data.
      RESULTS: All but 2 patients had an increase in nasal volume of at least 5.1% (SD,
      4.6%). The largest value of 35.3% (SD, 45.8%) was measured anteriorly on the
      nasal floor, decreasing cranially and posteriorly. This correlated with the V
      shaped opening of the sutura palatina. There was no significant correlation
      between increase in nasal volume and transversal expansion. CONCLUSIONS: Because
      most of the air we breathe passes over the lower nasal floor, SARME is likely to
      improve nasal breathing.

PMID- 20685534
TI  - Oral health-related quality of life in orthognathic surgery patients.
AB  - INTRODUCTION: In the last decade, an increasing number of studies focusing on the
      impact of oral deformities and illnesses on quality of life have been published.
      Our goal was to evaluate the impact of oral problems on quality of life in 3
      groups of adult patients in need of orthognathic-surgical treatment. METHODS: A
      total of 117 patients were recruited from the Clinic of Oral and Maxillofacial
      Surgery of the State University of Rio de Janeiro in Brazil: 20 in the initial
      phase, 70 in the presurgical phase (presurgical orthodontic preparation), and 27
      in the postsurgical phase. The impact of treatment phase on oral health-related
      quality of life was evaluated with the oral health impact profile (OHIP-14). OHIP
      14 scores were calculated by an additive method, and the participants were
      divided on the basis of level of impact into 2 groups: high impact (scores, >11)
      and low impact (scores, < or =11). RESULTS: Compared with patients in the
      postsurgical phase, those who needed orthognathic surgical treatment but had not
      yet begun it and those who were in the presurgical phase of treatment were 6.48
      and 3.14 times more likely, respectively, to experience a negative impact of
      their oral condition. CONCLUSIONS: Among those undergoing or anticipating
      orthognathic-surgical treatment, orthognathic surgery positively affects the
      patients' quality of life.

PMID- 20685535
TI  - Efficacy of a filled-resin sealant in preventing decalcification during
      orthodontic treatment.
AB  - INTRODUCTION: Enamel decalcification during orthodontic treatment is a persistent
      problem. Resin-based sealants have been developed to protect enamel from
      decalcification. The purpose of this in-vivo study was to compare the effect of a
      fluoride-releasing filled enamel sealant with that of an unfilled nonfluoride
      control. METHODS: A total of 177 teeth in 18 patients were evaluated over a
      period of 12 to 18 months. A split-mouth design was used; half the teeth were
      treated with the fluoride-releasing sealant (Pro Seal, Reliance Orthodontic
      Products, Itasca, Ill), and the contralateral teeth received the control
      (Transbond MIP, 3M Unitek, Monrovia, Calif). The teeth were photographed before
      (T1) and after (T2) treatment. A panel of 12 orthodontic faculty and residents
      evaluated the photographs for decalcification on a graded scale. RESULTS: Sixty
      nine percent of the teeth treated with Pro Seal showed progressive
      decalcification from T1 to T2 vs 72% of those treated with Transbond MIP. In the
      comparison of the contralateral paired teeth, there was a small average net
      disadvantage of -0.06 of a tooth per patient (95% CI, -0.97 to 0.85) for Pro Seal
      compared with Transbond MIP. That difference of 0.06 of a tooth is neither
      statistically significant (P = 0.90) nor clinically important. CONCLUSIONS: The 2
      products tested were equivalent in their inhibition of decalcification during
      orthodontic treatment. The additional time and expense of using the fluoride
      releasing sealant to prevent decalcification does not appear to be justified.

PMID- 20685536
TI  - Effects of 2 types of facemasks on condylar position.
AB  - INTRODUCTION: The aim of this study was to compare Delaire and Grummons
      protraction facemasks with a new articulator system (Amtech MG1, American
      Technologies, Brazil) that can record condylar positions. METHODS: Thirty-four
      patients treated with protraction facemask therapy were divided into 2 groups; 18
      were treated with the Delaire facemask (DFM) and 16 with the Grummons facemask
      (GFM). The observation periods were 8.5 months for the DFM group and 10 months
      for the GFM group. Mandibular position indicator (MPI) recordings were taken with
      the new articulator system and evaluated before and after the protraction
      facemask therapies. RESULTS: MPI recordings in the sagittal plane showed forward
      and downward movement from centric relation to maximum intercuspal position for
      both condyles at the beginning of treatment for most patients. After treatment,
      the discrepancy between centric relation and maximum intercuspation was less in
      the DFM group than in the GFM group. However, more compressive movement of the
      condyles through the glenoid fossa was observed in the DFM group. CONCLUSIONS:
      Although the centric slide amount decreased more with the Delaire facemask
      compared with the Grummons facemask, patients treated with the Delaire facemask
      must be monitored for signs and symptoms of temporomandibular joint disorder.

PMID- 20685537
TI  - Nickel release from new conventional stainless steel, recycled, and nickel-free
      orthodontic brackets: An in vitro study.
AB  - INTRODUCTION: The aim of this study was to compare the nickel released from 3
      kinds of orthodontic brackets: new conventional stainless steel, recycled
      stainless steel, and nickel-free brackets. METHODS: This in-vitro study was
      performed by using a classic batch procedure. Samples were immersed in artificial
      saliva at various acidities (pH 4.2, 6.5, 7.6) over an extended time interval
      (0.25, 1, 24, 48, and 120 hours). The amount of nickel released was determined by
      using an atomic absorption spectrophotometer and an inductively coupled plasma
      atomic emission spectrometer. Statistical analysis included a linear regression
      model for repeated measures, with calculation of Huber White robust standard
      errors to account for intrabracket correlation of data. For post-hoc comparisons,
      the Bonferroni correction was applied. RESULTS: The recycled brackets released
      the most nickel (74.02 +/- 170.29 microg per gram); the new stainless steel
      brackets released 7.14 +/- 20.83 microg per gram. The nickel-free brackets
      released the least nickel (0.03 +/- 0.06 microg per gram). All the differences
      among the groups were statistically significant (P = 0.000). CONCLUSIONS:
      Reconditioned brackets released the most nickel. Moreover, the highest nickel
      release was recorded in the 2 experiments performed at pH 4.2; it was lower at pH
      6.5 and 7.6. Conversely, no relevant differences were observed overall between
      the maxillary and mandibular arches.

PMID- 20685538
TI  - Sagittal and vertical occlusal cephalometric analyses of Pancherz: Norms for
      Chinese children.
AB  - INTRODUCTION: The aims of this research were to establish norms for the sagittal
      and vertical occlusal cephalometric analyses of Pancherz for Chinese children and
      compare them with those of a matched white sample. METHODS: The material
      comprised lateral cephalograms of a random sample of 405 southern Chinese
      children (age, 12 years; 200 boys, 205 girls) and an additional sample of 86
      British white children (age, 12 years; 43 boys, 43 girls) in Hong Kong. The
      radiographs were digitized twice. RESULTS: Statistically significant sex
      differences were found for 9 of 11 parameters in the sagittal occlusal analysis,
      and 6 of 10 in the vertical occlusal analysis in the Chinese sample, whereas
      there were no sex differences in the sagittal occlusal analysis and only 2
      differences in the vertical occlusal analysis in the white sample. Statistically
      significant ethnic differences were found for 5 parameters in boys and 8 in girls
      of the 11 parameters in the sagittal analysis. For the vertical analysis, 7 of 10
      parameters in both sexes differed significantly. CONCLUSIONS: For the sagittal
      and vertical occlusal analyses of Pancherz, separate sex-specific standards are
      needed for Chinese and white children.

PMID- 20685539
TI  - Predrilling of the implant site: Is it necessary for orthodontic mini-implants?
AB  - Mini-implants are becoming increasingly popular in orthodontic practice. However,
      there is still controversy about the need for implant-site preparation. This
      article reviews the current literature to answer the question: is predrilling is
      necessary for orthodontic mini-implants?

PMID- 20685540
TI  - Miniscrew-assisted nonsurgical palatal expansion before orthognathic surgery for
      a patient with severe mandibular prognathism.
AB  - A transverse maxillary deficiency in an adult is a challenging problem,
      especially when it is combined with a severe anteroposterior jaw discrepancy. The
      demand for nonsurgical maxillary expansion might increase as patients and
      clinicians try to avoid a 2-stage surgical procedure-surgically assisted rapid
      palatal expansion followed by orthognathic surgery-and detrimental periodontal
      effects and relapse. In this regard, a miniscrew-assisted rapid palatal expansion
      was devised and used to treat a 20-year-old patient who had severe transverse
      discrepancy and mandibular prognathism. Sufficient maxillary orthopedic expansion
      with minimal tipping of the buccal segment was achieved preoperatively, and
      orthognathic surgery corrected the anteroposterior discrepancy. The periodontal
      soundness and short-term stability of the maxillary expansion were confirmed both
      clinically and radiologically. Effective incorporation of orthodontic miniscrews
      for transverse correction might help eliminate the need for some surgical
      procedures in patients with complex craniofacial discrepancies by securing the
      safety and stability of the treatment, assuming that the suture is still patent.

PMID- 20685541
TI  - Orthodontic-surgical treatment of Class III malocclusion with extraction of an
      impacted canine and multi-segmented maxillary surgery.
AB  - Establishment of a treatment plan is based on efficacy and easy application by
      the clinician, and acceptance by the patient. Treatment of adult patients with
      Class III malocclusion might require orthognathic surgery, especially when the
      deformity is severe, with a significant impact on facial esthetics. Impacted
      teeth can remarkably influence treatment planning, which should be precise and
      concise to allow a reasonably short treatment time with low biologic cost. We
      report here the case of a 20-year-old man who had a skeletal Class III
      malocclusion and impaction of the maxillary right canine, leading to remarkable
      deviation of the maxillary midline; this was his chief complaint. Because of the
      severely deviated position of the impacted canine, treatment included extraction
      of the maxillary right canine and left first premolar for midline correction
      followed by leveling, alignment, correction of compensatory tooth positioning,
      and orthognathic surgery to correct the skeletal Class III malocclusion because
      of the severe maxillary deficiency. This treatment approach allowed correction of
      the maxillary dental midline discrepancy to the midsagittal plane and
      establishment of good occlusion and optimal esthetics.

PMID- 20685542
TI  - In-house precision bracket placement with the indirect bonding technique.

PMID- 20685543
TI  - Update on medical disorders in pregnancy. Foreword.

PMID- 20685544
TI  - Update on medical disorders in pregnancy. Preface.

PMID- 20685545
TI  - Pregestational diabetes.
AB  - The prevalence of preexisting diabetes in pregnancy is increasing largely because
      of an increase in type 2 diabetes. Outcomes of diabetic pregnancies for mother
      and newborn have improved greatly in recent decades from advances in
      understanding the disease process, improved education, and new treatment
      modalities delivered in a team approach. Nausea and vomiting from pregnancy and
      pregnancy-associated insulin resistance can make glycemic control a challenge.
      Care of women with preexisting diabetes demands careful monitoring in the
      preconception, prenatal, and peripartum periods.

PMID- 20685546
TI  - Asthma in pregnancy: pathophysiology, diagnosis and management.
AB  - Asthma is a common, potentially serious, even life-threatening, chronic medical
      condition seen amongst nearly all groups of patients, regardless of ethnicity and
      socioeconomic circumstances. This article addresses the group of pregnant women
      with symptomatic asthma as well as those whose asthma is asymptomatic as a result
      of good control. The incidence, the pathophysiologic changes of pregnancy, and
      the interplay between these changes and asthma are reviewed in this article. The
      classification of these patients and appropriate management strategies are
      discussed.

PMID- 20685547
TI  - Diagnosis and management of thyroid disease in pregnancy.
AB  - Thyroid disease is common, affecting 1% to 2% of pregnant women. Pregnancy may
      modify the course of thyroid disease, and pregnancy outcomes can depend on
      optimal management of thyroid disorders. Consequently, obstetric providers must
      be familiar with thyroid physiology and management of thyroid diseases in
      pregnancy. Following a brief overview of physiology, this article provides an in
      depth review of diagnosis and management of the spectrum of thyroid disease
      occurring in pregnancy. Recommendations for screening and treatment of hypo- and
      hyperthyroidism are summarized. Specific attention is given to the limitations of
      current research and the status of ongoing work.

PMID- 20685548
TI  - Management of renal disease in pregnancy.
AB  - Although renal disease in pregnancy is uncommon, it poses considerable risk to
      maternal and fetal health. This article discusses renal physiology and assessment
      of renal function in pregnancy and the effect of pregnancy on renal disease in
      patients with diabetes, lupus, chronic glomerulonephritis, polycystic kidney
      disease, and chronic pyelonephritis. Renal diseases occasionally present for the
      first time in pregnancy, and diagnoses of glomerulonephritis, acute tubular
      necrosis, hemolytic uremic syndrome, and acute fatty liver of pregnancy are
      described. Finally, therapy of end-stage renal disease in pregnancy, dialysis,
      and renal transplantation are reviewed.

PMID- 20685549
TI  - Pregnancy in the renal transplant recipient.
AB  - March 10th, 1958, is the birthday of the first baby born to a kidney transplant
      recipient. The pregnancy went to term and the baby was delivered by cesarean
      section for fear that a vaginal birth could adversely affect the allograft kidney
      sitting in the iliac fossa. Undoubtedly, this pregnancy more than 50 years ago
      was considered high risk because of its pioneering nature. However, given that
      the transplant recipient had received her kidney from her identical twin sister
      approximately 2 years before and was not taking any immunosuppressive
      medications, the pregnancy was associated with far fewer risks than most
      pregnancies in transplant recipients of today. Not only are immunosuppressants
      now available that have potential adverse affects on the developing fetus but
      also many kidney transplant recipients have kidney function that is suboptimal.
      Although thousands of women with kidney transplants have successfully delivered
      healthy babies, many new issues must be considered during a transplant
      recipient's pregnancy compared with 50 years ago. These issues are discussed in
      this article.

PMID- 20685550
TI  - Sickle cell disease in pregnancy.
AB  - The term sickle cell disease (SSD) encompasses several different sickle
      hemoglobinopathies. The ability to predict the clinical course of SSD during
      pregnancy is difficult. This article examines pregnancy-associated complications
      in SSD and the management of sickle cell disorders in pregnant women. Outcomes
      have improved for pregnant women with SSD and nowadays the majority can achieve a
      successful live birth. However, pregnancy is still associated with an increased
      incidence of morbidity and mortality. Optimal management during pregnancy should
      be directed at preventing pain crises, chronic organ damage, optimization of
      fetal health and minimizing early maternal mortality using a multidisciplinary
      team approach and prompt, effective and safe relief of acute pain episodes.

PMID- 20685551
TI  - Abnormal placentation, angiogenic factors, and the pathogenesis of preeclampsia.
AB  - Preeclampsia is a common complication of pregnancy with potentially devastating
      consequences to both the mother and the baby.It is the leading cause of maternal
      deaths in developing countries. In developed countries it is the major cause of
      iatrogenic premature delivery and contributes significantly to increasing health
      care cost associated with prematurity. There is currently no known treatment for
      preeclampsia; ultimate treatment involves delivery of the placenta. Although
      there are several risk factors (such as multiple gestation or chronic
      hypertension), most patients present with no obvious risk factors. The molecular
      pathogenesis of preeclampsia is just now being elucidated. It has been proposed
      that abnormal placentation and an imbalance in angiogenic factors lead to the
      clinical findings and complications seen in preeclampsia. Preeclampsia is
      characterized by high levels of circulating antiangiogenic factors such as
      soluble fms-like tyrosine kinase-1 and soluble endoglin, which induce maternal
      endothelial dysfunction. These soluble factors are altered not only at the time
      of clinical disease but also several weeks before the onset of clinical signs and
      symptoms. Many methods of prediction and surveillance have been proposed to
      identify women who will develop preeclampsia, but studies have been inconclusive.
      With the recent discovery of the role of angiogenic factors in preeclampsia,
      novel methods of prediction and diagnosis are being developed to aid
      obstetricians and midwives in clinical practice. This article discusses the role
      of angiogenic factors in the pathogenesis, prediction, diagnosis, and possible
      treatment of preeclampsia.

PMID- 20685552
TI  - Update on gestational diabetes.
AB  - As the rate of obesity increases in adolescent and adult women in the United
      States, practitioners of obstetrics see higher rates of gestational diabetes.
      Recent clinical studies suggest that women with gestational diabetes have
      impaired pancreatic beta-cell function and reduced beta-cell adaptation resulting
      in insufficient insulin secretion to maintain normal glycemia. Despite recent
      evidence that even mild hyperglycemia is associated with adverse pregnancy
      outcomes, controversies still exist in screening, management, and treatment of
      gestational diabetes. Initial studies regarding glyburide for treatment of
      gestational diabetes are promising. Overall, only about half of the women with
      gestational diabetes are screened in the postpartum period, an ideal time for
      education and intervention, to decrease incidence of glucose intolerance and
      progression to type 2 diabetes.

PMID- 20685553
TI  - Cholestasis of pregnancy.
AB  - Intrahepatic cholestasis (ICP) of pregnancy is a disease that is likely
      multifactorial in etiology and has a prevalence that varies by geography and
      ethnicity. The diagnosis is made when patients have a combination of pruritus and
      abnormal liver-function tests. It is associated with a high risk for adverse
      perinatal outcome, including preterm birth, meconium passage, and fetal death. As
      of yet, the cause for fetal death is unknown. Because fetal deaths caused by ICP
      appear to occur predominantly after 37 weeks, it is suggested to offer delivery
      at approximately 37 weeks. Ursodeoxycholic acid appears to be the most effective
      medication to improve maternal pruritus and liver-function tests; however, there
      is no medication to date that has been shown to reduce the risk for fetal death.

PMID- 20685554
TI  - Update on peripartum cardiomyopathy.
AB  - Although multiple mechanisms have been postulated, peripartum cardiomyopathy
      (PPCM) continues to be a cardiomyopathy of unknown cause. Multiple risk factors
      exist and the clinical presentation does not allow differentiation among
      potential causes. Although specific diagnostic criteria exist, PPCM remains a
      diagnosis of exclusion. Treatment modalities are dictated by the clinical state
      of the patient, and prognosis is dependent on recovery of function. Randomized
      controlled trials of novel therapies, such as bromocriptine, are needed to
      establish better treatment regimens to decrease morbidity and mortality. The
      creation of an international registry will be an important step to better define
      and treat PPCM. This article discusses the pathogenesis, risk factors, diagnosis,
      management, and prognosis of this condition.

PMID- 20685555
TI  - Pregnancy after bariatric surgery.
AB  - The incidence of obesity is increasing rapidly, and it affects a greater
      proportion of women than men. Unfortunately, obesity has a negative impact on
      women's reproductive health, including increased adverse perinatal outcomes.
      Weight loss surgery, also known as bariatric surgery, is performed in many
      hospitals, and can allow for significant weight loss and improvement in medical
      comorbidities such as diabetes and hypertension. A woman who becomes pregnant
      after bariatric surgery usually has an uncomplicated pregnancy but requires
      special attention to some complications that can occur after these procedures.
      This article reviews the perinatal outcomes and provides recommendations for care
      regarding the unique issues that arise during a pregnancy after bariatric
      surgery.

PMID- 20685556
TI  - Selected viral infections in pregnancy.
AB  - This article reviews the impact of seasonal influenza on pregnancy with
      particular emphasis on the 2009 novel H1N1 pandemic. Antiviral therapy for
      influenza, as well as recommendations and safety data on vaccination are
      discussed. In addition, the impact of hepatitis A, B, and C in pregnancy is
      addressed with a focus on prevention and treatment strategies for hepatitis B and
      C.

PMID- 20685557
TI  - Thromboprophylaxis in pregnancy: who and how?
AB  - Venous thrombosis and embolism (VTE) is one of the most common, serious
      complications associated with pregnancy, and now ranks as a leading cause of
      maternal morbidity and mortality in developed countries. Information regarding
      the association of VTE with acquired and heritable thrombophilias has greatly
      expanded in the last 20 years, adding a new layer of complexity to decisions
      about thromboprophylaxis. The objective of this review is to detail which
      patients are at clinically important increased risk for VTE, are candidates for
      thrombophilia screening, and warrant thromboprophylaxis. Recommended management
      regimens for use in specific patient subgroups are also provided.

PMID- 20685558
TI  - Ethical issues in obstetrics.
AB  - Obstetricians must become comfortable addressing the ethical issues involved in
      clinical obstetrics and therefore must have an understanding of the key elements
      of clinical medical ethics. Balancing the principles of medical ethics can guide
      clinicians toward solutions to ethical dilemmas encountered in the care of
      pregnant women. The purpose of this article is to review the ethical foundations
      of clinical practice, recognize the ethical issues obstetricians face every day
      in caring for patients, and facilitate decision making. This article discusses
      the relevant ethical principles, identifies unique features of obstetrical
      ethics, examines ethical principles as they apply to pregnant patient and her
      fetus, and thereby, provides a conceptual framework for considering ethical
      issues and facilitating decision making in clinical obstetrics.

PMID- 20685559
TI  - Treatment of venous disease. Introduction.

PMID- 20685560
TI  - The importance of uniform venous terminology in reports on varicose veins.
AB  - There is a need for a standardized consistent language in vascular surgery that
      allows easy flow of information and comparison of results among clinicians.
      Beginning with current nomenclature, a common language serves as a framework for
      more detailed efforts. Understanding the outcomes assessment tools available
      provides the opportunity for universal outcomes reporting. Data collected at
      widespread points can then be fairly compared, and common goals of therapy can be
      determined. Common outcomes that have demonstrated verifiable trends and
      reproducibility should be subjected to the rigors of evidence-based questioning.
      The resultant standards of care and expectations of therapy are then confidently
      presented for everyday practice and ongoing research.

PMID- 20685561
TI  - Evaluation of varicose veins: what do the clinical signs and symptoms reveal
      about the underlying disease and need for intervention?
AB  - Varicose veins and associated venous insufficiency are among the most common
      vascular conditions requiring specialist evaluation and treatment. Over 80% of
      people studied in a population based evaluation were found to have visible
      evidence of venous disease. In this article, the epidemiology of venous disease
      will be reviewed with specific attention to the common symptom patterns displayed
      by patients with superficial venous disease. Based on physical examination, the
      clinician can determine the likely sites of venous insufficiency and efficiently
      direct use of various diagnostic modalities, such as duplex ultrasound. The
      importance of the CEAP clinical classification will be discussed as a guide to
      choosing therapy from the multitude of available options for patients with venous
      insufficiency.

PMID- 20685562
TI  - Importance of ultrasound evaluation in the diagnosis of venous insufficiency:
      guidelines and techniques.
AB  - Recent advances in the treatment of venous insufficiency have led to an increased
      utilization of venous ultrasonography by practitioners. Knowing the fundamentals
      of anatomy and physiology are essential to be successful. This article reviews
      the common uses of ultrasonagraphy for the examination of the lower extremity
      venous system.

PMID- 20685563
TI  - Radiofrequency ablation: evolution of a treatment.
AB  - Superficial venous insufficiency of the lower extremities is a common affliction.
      There are several modalities available to the clinician to treat this problem.
      This article specifically examines the technique of radiofrequency ablation in
      the treatment of superficial venous insufficiency. The evolution of the catheters
      used in radiofrequency ablation is discussed in detail. The mechanism of action
      of the radiofrequency energy on the vein wall is explained. Several technical
      aspects of the technique, such as temperature set point and pull-back speed are
      described. The importance of tumescent anesthesia and its role in reducing
      complications are illustrated. Short- and long-term results of radiofrequency
      ablation are compared to results with both operative therapy or endovenous laser
      therapy, the results are similar if not better. Complications of radiofrequency
      ablation therapy are discussed, emphasizing the advent of tumescent anesthesia
      and the resultant drop in paresthesias. Outcome analysis of radiofrequency
      ablation is shown to have positive effects on both clinical-etiologic-anatomic
      pathophysiologic class and venous clinical severity score. Finally other
      considerations, including billing and necessary supplies, are summarized. In
      summary, radiofrequency ablation is shown to be a safe and effective modality in
      the treatment of superficial venous insufficiency.

PMID- 20685564
TI  - Laser treatment of varicose veins: order out of chaos.
AB  - Varicose veins of the lower extremity are commonly encountered by vascular
      surgeons. Historically, the standard treatment of varicose veins has been high
      ligation and stripping of the great saphenous vein. Endovenous ablation
      techniques have been adopted by many surgeons over the past few years. Techniques
      of endovenous laser surgery are reviewed, as are the common complications and
      expected outcomes.

PMID- 20685565
TI  - Management of secondary varicosities.
AB  - Physicians have several options to treat varicose veins that remain after
      successful axial vein ablation. Foam sclerotherapy is effective for all sorts of
      veins, but may become less effective and have a higher risk of complications when
      treating large diameter veins. Endovenous laser and radiofrequency ablation can
      be used to treat nontortuous tributaries. Ambulatory phlebectomy is useful for
      visible and palpable veins.

PMID- 20685566
TI  - Diagnosis and current management of incompetent perforator veins.
AB  - For nearly a century, surgeons have recognized that incompetent perforator veins
      (IPVs) likely play a role in the development of venous pathology. Although
      surgical management of IPVs has improved significantly since Linton first
      described his approach in 1938, little evidence exists that clearly defines the
      role of IPV interruption as a modern treatment for complicated venous
      insufficiency of the lower extremity. The purpose of this article is to review
      the literature in an attempt to clarify the role for IPV therapies as either
      adjunct or independent treatment for complicated venous insufficiency.
      Additionally, a summary of IPV diagnosis, patient selection, and current ablative
      therapies will hopefully serve as a guide for surgeons who manage venous disease.

PMID- 20685567
TI  - CHIVA.
AB  - Based on a theoretical hemodynamic model, CHIVA (conservative hemodynamic cure
      for venous insufficiency) is an ultrasound-guided, minimally invasive surgical
      strategy performed under local anesthesia for the treatment of patients with
      varicose vein disease. After careful duplex mapping, the surgeon performs flush
      ligation procedures at the proximal origin of key points of reflux while
      meticulously maintaining superficial venous drainage to prevent varicosity
      recurrence. The saphenous veins are preserved. The strategy has been shown in
      studies to be safe and effective.

PMID- 20685568
TI  - What is the current role of foam sclerotherapy in treating reflux and
      varicosities?
AB  - Foam sclerotherapy is not a defined procedure nor is the product uniform or
      licensed for use but it is now accepted practice in most territories worldwide.
      Foam sclerotherapy has been used to treat a wide range of venous conditions from
      the closure of incompetent great saphenous trunk veins to telangiectasia and from
      venous malformations to hemorrhoids with good outcomes being reported. There is a
      rapidly expanding body of literature supporting its safety and efficacy as well
      as a few case histories of serious complications. This article will focus on the
      current role of foam sclerotherapy in the treatment of varicose veins.

PMID- 20685570
TI  - Epicardium and myocardium originate from a common cardiogenic precursor pool.
AB  - During development, the epicardium, an epithelial layer that covers the heart,
      gives rise to a large portion of the nonmyocardial cells present in the heart.
      The epicardium arises from a structure, called the proepicardium, which forms at
      the inflow of the developing heart. By epithelial-to-mesenchymal transformation,
      mesenchymal cells are formed that will subsequently populate the stroma of the
      proepicardium and the subepicardium. Based on labeling analysis, the
      proepicardium and part of the myocardium have been shown to be derived from a
      common cardiogenic precursor population. In this review, we will discuss the
      common cardiogenic origin of proepicardial and myocardial cells, the underlying
      processes and factors that play a role in the separation of the lineages, and
      their potential role in cardiac regenerative approaches.

PMID- 20685571
TI  - Glucagon-like peptide 1--a cardiologic dimension.
AB  - Recent experimental data suggest glucagon-like peptide 1 (GLP-1) and its analogs
      to have direct effects on the cardiovascular system, in addition to their classic
      glucoregulatory actions. These direct effects may be cardioprotective,
      contractility augmenting, and vasorelaxant. A few preliminary clinical trials
      appear to support a mechanical function improvement after GLP-1 administration to
      patients with a weakened left ventricle. Based on animal studies, diminished
      lethal injury to the postischemic reperfused myocardium appears to be a
      particularly promising prospect, awaiting to be tested in clinical settings.

PMID- 20685572
TI  - Cardiac muscle ring finger-1--friend or foe?
AB  - The ubiquitin proteasome system plays a role in regulating protein activity and
      is integral to the turnover of damaged and worn proteins. In this review, we
      discuss the recently described relationship between the ubiquitin proteasome
      system and the cardiac creatine kinase/phosphocreatine shuttle, an essential
      component of adenosine triphosphate generation and energy shuttling within the
      heart. The ubiquitin ligase muscle ring finger-1 (MuRF1) binds creatine kinase,
      leading to its ubiquitination and possible degradation. Muscle ring finger-1 may
      also be integral in the regulation of creatine kinase activity in vivo. Because
      there is a close relationship between the cardiac creatine kinase/phosphocreatine
      shuttle activity and heart failure, these findings suggest that MuRF1's role in
      protein quality control of creatine kinase may be vital to the regulation and
      maintenance of cardiac energetics to protect against heart failure.

PMID- 20685574
TI  - Endothelial progenitor cells in pulmonary arterial hypertension.
AB  - Pulmonary arterial hypertension (PAH) is a progressive disease characterized by
      ongoing endothelial dysfunction and vascular remodeling. Endothelial progenitor
      cells (EPCs), mobilized from the bone marrow and resident locally in the lung,
      are thought to be important in maintaining vascular homeostasis; and there is
      growing interest in the potential therapeutic use of EPCs in PAH. Putative
      progenitor cells have also been localized to vascular lesions in the lungs of
      patients with PAH, raising questions about their role in vascular remodeling and
      disease progression. Further studies are required to determine the identity,
      origin, and function of progenitor cells in pulmonary vascular lesions and to
      establish whether the mobilization and recruitment of EPCs in the hypertensive
      pulmonary vascular system represent a protective process and/or involvement in
      the pathogenesis of PAH.

PMID- 20685573
TI  - Sodium channel molecular conformations and antiarrhythmic drug affinity.
AB  - Class I cardiac antiarrhythmic drugs, for example, lidocaine, mexiletine,
      flecainide, quinidine, and procainamide, continue to play an important role in
      the therapy for cardiac arrhythmias because of the presence of use-dependent
      block. Lidocaine, as well as related drugs such as mepivacaine, bupivacaine, and
      cocaine, also belong to the class of medications referred to as local
      anesthetics. In this review, we will consider lidocaine as the prototypical
      antiarrhythmic drug because it continues to be widely used both as an
      antiarrhythmic drug (first used as an antiarrhythmic drug in 1950) as well as a
      local anesthetic agent. Both of these clinical uses depend upon block of sodium
      current (I(Na)), but it is the presence of use-dependent I(Na) block, that is, an
      increasing amount of block at faster heart rates, which enables a local
      anesthetic agent to be a useful antiarrhythmic drug. Although many early studies
      investigated the action of antiarrhythmic drugs on Na currents, the availability
      of site-directed mutant Na channels has enabled for major advances in
      understanding their mechanisms of action based upon molecular conformations of
      the Na channel.

PMID- 20685575
TI  - Calmodulin kinase II, sarcoplasmic reticulum Ca2+ leak, and atrial fibrillation.
AB  - Although it is generally accepted that excitation-contraction coupling is
      defective in patients with atrial fibrillation, the underlying cellular
      mechanisms remain incompletely understood. Recent studies suggest that abnormal
      sarcoplasmic reticulum calcium "leak" via ryanodine receptors contributes to
      atrial arrhythmogenesis. Increased activity of the enzyme calmodulin kinase II
      (CaMKII) and, specifically, enhanced CaMKII phosphorylation of ryanodine
      receptors appear to play a critical role in the induction and perhaps maintenance
      of atrial fibrillation. In this review, we will summarize new insights into the
      role of enhanced CaMKII in sarcoplasmic reticulum calcium leak and atrial
      arrhythmogenesis during atrial fibrillation.

PMID- 20685576
TI  - Introduction: non-small-cell lung cancer and pleural malignancies: the end of the
      era of therapeutic nihilism?

PMID- 20685577
TI  - Radiogenomics predicting tumor responses to radiotherapy in lung cancer.
AB  - The recently developed ability to interrogate genome-wide data arrays has
      provided invaluable insights into the molecular pathogenesis of lung cancer.
      These data have also provided information for developing targeted therapy in lung
      cancer patients based on the identification of cancer-specific vulnerabilities
      and set the stage for molecular biomarkers that provide information on clinical
      outcome and response to treatment. In addition, there are now large panels of
      lung cancer cell lines, both non-small-cell lung cancer and small-cell lung
      cancer, that have distinct chemotherapy and radiation response phenotypes. We
      anticipate that the integration of molecular data with therapy response data will
      allow for the generation of biomarker signatures that predict response to
      therapy. These signatures will need to be validated in clinical studies, at first
      retrospective analyses and then prospective clinical trials, to show that the use
      of these biomarkers can aid in predicting patient outcomes (eg, in the case of
      radiation therapy for local control and survival). This review highlights recent
      advances in molecular profiling of tumor responses to radiotherapy and identifies
      challenges and opportunities in developing molecular biomarker signatures for
      predicting radiation response for individual patients with lung cancer.

PMID- 20685579
TI  - Image guidance in non-small cell lung cancer.
AB  - New imaging technologies have advanced our ability to treat lung cancers through
      enhanced and extended visualization of the tumor as well as patient and treatment
      response. Image guidance can reduce uncertainty by increasing precision and
      accuracy through improved patient selection, target delineation, and improved
      knowledge of nodal involvement. Conformal imaging-based radiotherapy (RT) can
      allow dose escalation. In the future, imaging may allow adaptive RT to be
      exploited in selected patients, especially those with large geometric changes
      occurring during RT. Furthermore, functional imaging, although in its infancy,
      has the potential to significantly improve RT, from RT planning and delivery to
      outcome assessment.

PMID- 20685580
TI  - The treatment of early-stage disease.
AB  - For medically operable patients with stage I non-small-cell lung cancer (NSCLC),
      lobectomy or pneumonectomy remains the standard of care. The utility of
      radiotherapy or chemotherapy after major pulmonary resection remains unproven,
      though clinical and biological models may identify subgroups most likely to
      benefit. Limited resection results in higher rates of local failure for all but
      the most highly selected patients, though brachytherapy may reduce this risk. In
      medically inoperable patients, conventional radiotherapy results in control rates
      less than half of that achieved by surgery. Dose escalation and hypofractionation
      are technically feasible with modern planning and delivery, and appear to improve
      control rates compared with conventional radiotherapy. Stereotactic body
      radiotherapy represents a major advance for the treatment of stage I NSCLC, with
      early reports documenting excellent control rates and a low risk of severe
      toxicity. In this review we address each of these points, with particular
      emphasis on recent or ongoing prospective trials.

PMID- 20685578
TI  - The tumor microenvironment in non-small-cell lung cancer.
AB  - The tumor microenvironment (TME) of NSCLC is heterogeneous with variable blood
      flow through leaky immature vessels resulting in regions of acidosis and hypoxia.
      Hypoxia has been documented in NSCLC directly by polarographic needle electrodes
      and indirectly by assessing tissue and plasma hypoxia markers. In general,
      elevated expression of these markers portends poorer outcomes in NSCLC. Impaired
      vascularity and hypoxia can lead to increased metastasis and treatment
      resistance. Compounds that directly target hypoxic cells such as tirapazamine
      have been tested in clinical trials for NSCLC with mixed results. Preclinical
      data, however, suggest other ways of exploiting the abnormal TME in NSCLC for
      therapeutic gain. The inhibition of hypoxia-inducible factor-1alpha or vascular
      endothelial growth factor may increase local control after radiation. Inhibitors
      of the epidermal growth factor receptor (EGFR)/phosphatidylinositol 3-kinase
      (PI3K)/Akt pathway, such as erlotinib or PI-103, may "normalize" tumor vessels,
      allowing for increased chemotherapy delivery or improved oxygenation and
      radiation response. To select patients who may respond to these therapies and to
      evaluate the effects of these agents, a noninvasive means of imaging the TME is
      critical. Presently, there are several promising modalities to image hypoxia and
      the tumor vasculature; these include dynamic perfusion imaging and positron
      emission tomography scanning with radiolabled nitroimidazoles.

PMID- 20685581
TI  - Combined modality therapy for stage III non-small-cell lung cancer.
AB  - With 40,000 to 50,000 patients diagnosed annually, stage III lung cancer
      represents approximately one third of all non-small-cell lung cancer cases. It is
      a heterogeneous disease stage encompassing stage IIIa, for which surgery in
      combination with chemotherapy and/or radiation therapy represents a treatment
      strategy for select patients, and stage IIIb, for which chemoradiation represents
      the prevailing standard of care. Overcoming unacceptably high rates of
      intrathoracic tumor failures remains a central obstacle. Current clinical trial
      efforts focus on targeted therapies, new chemotherapy regimens, dose-escalated
      radiation therapy, and improvements in radiation therapy treatment delivery.

PMID- 20685582
TI  - Current status of postoperative radiation for non-small-cell lung cancer.
AB  - Radiation therapy can increase local control and potentially improve survival in
      patients who have had resection for lung cancer. However, radiation therapy also
      has the potential to cause serious toxicity and should not be indiscriminately
      delivered. The PORT meta-analysis clearly illustrated the potential toxic effects
      of postoperative radiotherapy (PORT). Modern three-dimensional radiation
      treatment planning facilitates the design of treatment fields that more
      conformally treat the site(s) at risk, and this appears, based on limited data,
      to improve the therapeutic ratio of PORT. Moreover, systemic and local therapies
      are likely synergistic, and thus improvements in systemic staging and treatment
      may increase the ability of local therapies to improve overall survival.
      Therefore, a reassessment of the utility of postoperative radiation therapy using
      limited fields and modern techniques is warranted.

PMID- 20685583
TI  - Radiation pulmonary toxicity: from mechanisms to management.
AB  - The goal of radiation therapy is to reduce or eliminate tumor burden while
      sparing normal tissues from long-term injury. Thoracic radiation presents a
      unique challenge because of the inherent sensitivity of normal lung tissue to
      radiation. Damage to normal lung tissue presents a major obstacle in the
      treatment of individuals. To overcome this problem, a number of strategies are
      being used, including the modulation of dose volume, the use of image-guided
      radiotherapy, and the use of agents designed to reduce lung injury from
      radiation. Herein we discuss our current knowledge of the molecular and cellular
      events that occur after radiation therapy, the clinical manifestations of
      radiation-induced lung injury, current strategies to minimize lung injury, and
      recent experimental methods to reduce lung injury and their potential for
      translation into the clinic.

PMID- 20685584
TI  - Pleural malignancies.
AB  - Pleural malignancies, primary or metastatic, portend a grim prognosis. In
      addition to the serious oncologic implications of a pleural malignancy, these
      tumors can be highly symptomatic. A malignant pleural effusion can cause dyspnea,
      secondary to lung compression, or even tension physiology from a hydrothorax
      under pressure. The need to palliate these effusions is a seemingly
      straightforward clinical scenario, but with nuances that can result in disastrous
      complications for the patient if not attended to appropriately. Solid pleural
      malignancies can cause great pain from chest wall invasion or can cause a myriad
      of morbid symptoms because of the invasion of thoracic structures, such as the
      heart, lungs, or esophagus. This article reviews pleural malignancies, the purely
      palliative treatments, and the treatments that are performed with definitive
      (curative) intent.

PMID- 20685586
TI  - Modulation of ingestive behavior and gastrointestinal motility by ghrelin in
      diabetic animals and humans.
AB  - Acyl ghrelin, a 28-amino acid peptide hormone, is the endogenous cognate ligand
      for the growth hormone secretagogue receptor. Ghrelin is involved in stimulating
      growth hormone release, eliciting feeding behavior, inducing adiposity and
      stimulating gastrointestinal motility. Ghrelin is unique for its post
      translational modification of O-n-octanoylation at serine 3 through ghrelin O
      acyltransferase, and is the only peripheral signal to enhance food intake. Plasma
      ghrelin levels manifest "biphasic changes" in diabetes mellitus (DM). In the
      early stage of DM, the stomach significantly increases the secretion of ghrelin
      into the plasma, and elevated plasma ghrelin levels are correlated with diabetic
      hyperphagic feeding and accelerated gastrointestinal motility. In the late stage
      of DM, plasma ghrelin levels may be lower, which might be linked with
      anorexia/muscle wasting, delayed gastrointestinal transit, and even
      gastroparesis. Therefore, the unique ghrelin system may be the most important
      player compared to the other hindgut hormones participating in the "entero
      insular axis". Further studies using either knockdown or knockout of ghrelin gene
      products and ghrelin O-acyltransferase may unravel the pathogenesis of DM, and
      show benefits in combating this disease and metabolic syndrome.

PMID- 20685587
TI  - Can we predict the death of neurosurgical patients in intensive care units?

PMID- 20685588
TI  - Health effects of medical radiation on cardiologists who perform cardiac
      catheterization.

PMID- 20685589
TI  - Diabetes and 15-year cardiovascular mortality in a Chinese population:
      Differential impact of hypertension and metabolic syndrome.
AB  - BACKGROUND: It remains unclear if the risk for cardiovascular (CV) mortality in
      patients with diabetes mellitus (DM) is equivalent to that in patients with a
      history of cardiac disease in Asian populations. The aims of the present study
      were to investigate whether or not non-heart disease (HD) DM subjects have a
      similar risk of CV mortality as HD patients without DM (non-DM HD), and whether
      or not hypertension (HT) or metabolic syndrome (MS) is a CV mortality marker for
      diabetic subjects identified from a community-based population. METHODS: We
      followed 11,058 Chinese people aged > or = 30 years on Kinmen island for a median
      of 15.0 years. RESULTS: The age-, sex- and smoking-adjusted hazard ratios for CV
      mortality were 3.56 [95% confidence interval (CI): 1.99-6.36] for DM subjects
      with HD, 1.64 (95% CI: 1.25-2.16) for DM without HD (non-HD DM) subjects, and
      1.63 (95% CI: 1.09-2.44) for non-DM HD patients, when compared with subjects
      without DM and HD. Among the 827 non-HD DM subjects identified at the baseline
      survey, the age-, sex- and smoking-adjusted hazard ratios for CV mortality were
      2.36 (95% CI: 1.30-4.28) for the presence versus absence of HT, and 1.23 (95% CI:
      0.65-2.34) for the presence versus absence of MS. CONCLUSION: Non-HD DM subjects
      had a similar risk of CV mortality to non-DM HD subjects in this Chinese
      population. The presence of HT but not MS substantially increased CV mortality
      risk in the DM subjects.

PMID- 20685590
TI  - Superiority of nitinol piston over conventional prostheses in stapes surgery:
      first comparative results in the Chinese population in Taiwan.
AB  - BACKGROUND: A growing number of studies conducted on stapes surgery have
      suggested that firm and adequate attachment of the prosthesis onto the long
      process of the incus plays a key role in surgical success. For this reason, a new
      prosthesis made of Nitinol characterized by "self-crimping" has been developed.
      Although better postoperative outcomes achieved with a Nitinol piston have been
      previously confirmed, the superiority of the Nitinol piston over the conventional
      manual-crimping prostheses remains controversial. The aim of this study was to
      determine the advantages of the Nitinol piston with regard to hearing
      improvement. METHODS: We retrospectively compared postoperative hearing in
      otosclerosis surgeries with the Nitinol piston versus the manual-crimping
      prostheses. Sixteen surgeries with Nitinol pistons (carried out between April
      2007 and August 2009) and 21 surgeries with conventional prostheses (carried out
      between January 2004 and January 2009) were evaluated. All patients received pure
      tone audiograms preoperatively and postoperatively. RESULTS: In the Nitinol
      piston group, the air-bone gap (ABG) average (7.92 + or - 6.75 dBHL) was
      significantly smaller postoperatively than preoperatively (26.79 + or - 8.33
      dBHL, p < 0.001). Similarly, the ABG average for the conventional piston group
      (13.09 + or - 6.99 dBHL) was significantly smaller postoperatively than
      preoperatively (26.19 + or - 6.76 dBHL, p < 0.001). Although both groups
      demonstrated an improvement in average ABG postoperatively, the Nitinol piston
      group showed a greater improvement than the conventional piston group (p =
      0.018). Additionally, ABG closure within 10 dB was attained in significantly more
      patients (75%) in the Nitinol piston group compared with the conventional piston
      group (33.3%, p = 0.012). CONCLUSION: The Nitinol piston has a distinct advantage
      over conventional prostheses, providing an easier, safer and more effective
      treatment option in otosclerosis surgery. To our knowledge, this is the first
      comparative analysis of hearing results of the Nitinol piston with conventional
      prostheses in the Chinese population in Taiwan. In this population, there is a
      much lower prevalence of otosclerosis, leading to a lack of surgical experience
      in otosclerosis surgery, even at large medical centers. This may explain, in
      part, the relative lack of studies conducted on stapes prostheses in Asian
      patients. Therefore, our preliminary research may provide a reference for future
      investigations on stapes surgery in Asian patients with otosclerosis based on
      ethnic differences.

PMID- 20685591
TI  - Experience of varicocele management during ipsilateral inguinal herniorrhaphy: a
      prospective study.
AB  - BACKGROUND: This was a prospective study to evaluate the experience of varicocele
      management during ipsilateral herniorrhaphy in an inpatient urology setting.
      METHODS: A total of 65 patients with varicocele and inguinal hernia scheduled for
      herniorrhaphy were included for evaluation. They were categorized into 3 groups.
      Group 1 (n = 20) had painful varicocele and underwent simultaneous herniorrhaphy
      and varicocelectomy; group 2 (n = 20) had asymptomatic varicocele and received
      simultaneous herniorrhaphy and varicocelectomy; and group 3 (n = 25) had
      asymptomatic varicocele and underwent herniorrhaphy only. We used the Bassini
      method for herniorrhaphy and inguinal microsurgical varicocelectomy for
      varicocele. Varicocele was diagnosed by physical examination and further
      confirmed by Doppler ultrasonography. RESULTS: The mean follow-up was 30.2 months
      (range, 6-56 months). Of the 20 subjects in group 1, complete resolution of
      scrotal pain was noticed in 14 (70%), and 2 (10%) had hydrocele after
      varicocelectomy. Of the 20 patients in group 2, 1 (5%) had hydrocele after
      surgery, and no hydrocele was noticed in group 3 after surgery. Mean operation
      time was significantly longer in group 1 (70.5 + or - 15.2 minutes) and group 2
      (69.8 + or - 14.5 minutes) than in group 3 (38.2 + or - 17.2 minutes). One case
      in group 1 had recurrent varicocele 6 months after surgery. Of the 25 subjects in
      group 3, 2 (8%) developed painful varicocele during the follow-up period, and
      both of them had indirect inguinal hernia and lower body mass index. CONCLUSION:
      Simultaneous herniorrhaphy and varicocelectomy are suggested for patients who
      have inguinal hernia and ipsilateral varicocele, but the average operation time
      is significantly longer and there is a higher rate of hydrocele than with
      herniorrhaphy only.

PMID- 20685592
TI  - Factors influencing the intention to utilize out-of-pocket health checkup
      services: A sample of citizens from 12 townships of Taichung County in Taiwan.
AB  - BACKGROUND: Taiwan started its National Health Insurance (NHI) system in 1995.
      However, until now, most cancer screening tests and preventive care have been out
      of-pocket (OOP) medical items excluded from the coverage of NHI. The aim of this
      study was to explore the factors influencing an individual's intention to utilize
      OOP health checkups. METHODS: A cross-sectional research method was adopted in
      this study. Based on the theory of planned behavior, a questionnaire was
      developed and used to survey purposively sampled residents (n = 940) from 12
      randomly selected townships in Taichung County, Taiwan, from August to September
      2006. Descriptive statics and linear regression were conducted to analyze the
      collected data. RESULTS: Our results showed that result evaluation (beta =
      0.092), behavioral beliefs (beta = 0.088), behavioral norms of people with
      experience in utilizing OOP health checkups (beta = 0.116), perceived convenience
      (beta = 0.273), and worry about illness and perceived health (beta = 0.110) were
      important factors influencing the intention to utilize OOP health checkups. Age,
      education and acceptable health checkup charges were also related. CONCLUSION:
      Reinforcing disease- and health checkup-related knowledge may positively
      influence an individual's intention to utilize OOP health checkups. In addition,
      improving perceived convenience and reducing disease-screening barriers can
      intensify the individual's intention to use OOP health checkups. The influence of
      age, education level and OOP checkup charges should also be taken into
      consideration when related policies are formulated.

PMID- 20685593
TI  - Coexistence of ankylosing spondylitis and systemic lupus erythematosus.
AB  - Coexistence of ankylosing spondylitis with connective tissue diseases is
      uncommon. We describe here the coexistence of ankylosing spondylitis and systemic
      lupus erythematosus in a 35-year-old man. He presented with a 4-year history of
      pain in the hip joint and lower spine, and he later developed a malar rash and
      discoid rash. Immunological tests revealed that antinuclear antibody and double
      stranded DNA antibody were positive. The human leukocyte antigen B27 antigen was
      also found to be positive. We propose that development of systemic lupus
      erythematosus in this case may have been due to low grade chronic inflammation.

PMID- 20685594
TI  - Sorafenib in metastatic renal cell carcinoma with sarcomatoid differentiation.
AB  - Targeted therapy in the management of metastatic renal cell cancer has been
      recently introduced to urology practice. The drugs used for management are used
      in a very limited number of patients and only for clear cell histology. We
      present a case where we administered sorafenib, a multikinase inhibitor of tumor
      cell proliferation and angiogenesis, to a patient with metastatic renal cell
      carcinoma of clear cell histology. We found that our results were different from
      those of previously reported studies, because sarcomatoid differentiation was
      evident in a histological examination of this case. There was an excellent
      response to sorafenib. This case report might provide evidence that
      antiangiogenic agents may be active in any histological type of renal cell
      carcinoma. However, there are no available data to demonstrate the duration of
      response and survival benefit.

PMID- 20685595
TI  - Subcutaneous and scrotal emphysema following suprapubic cystostomy in a patient
      with colovesical fistula.
AB  - Subcutaneous and scrotal emphysema are rare complications of suprapubic
      cystostomy. We present here a rare case of an 81-year-old man with colovesical
      fistula who had severe subcutaneous and scrotal emphysema after percutaneous
      suprapubic cystostomy was performed. We inserted a new Foley catheter via the
      urethra, removed the suprapubic cystostomy and incised his scrotal emphysema for
      open drainage. The patient's subcutaneous emphysema slowly healed.

PMID- 20685596
TI  - A rare complication after microlaryngeal surgery: subcutaneous emphysema and
      pneumomediastinum.
AB  - Microlaryngeal surgery is a common and relatively safe otorhinolaryngological
      surgery. Its common complications include pain and numbness of the tongue,
      bruising of the lip, and chipped teeth. However, reports of subcutaneous
      emphysema of the neck with pneumomediastinum following microlaryngeal surgery are
      rare. A 69-year-old female developed swelling of her left-side cheek and neck
      after microlaryngeal surgery for anterior glottic web. Palpation revealed
      subcutaneous emphysema and computed tomography demonstrated pneumomediastinum.
      The patient was managed conservatively, with complete resolution of symptoms
      within 2 weeks. Our observations suggest that emphysema likely resulted from
      increased intrapharyngeal pressure secondary to coughing, vomiting, straining, or
      manual ventilation after extubation provoked by disruption of the pharyngeal
      mucosa over the left anterior tonsillar pillar during insertion of the
      laryngoscope. Although microlaryngeal surgery is considered a relatively safe
      surgical procedure, it may be associated with significant complications. The
      procedure should be performed carefully to prevent mucosal injury.

PMID- 20685597
TI  - Distal marginal stenosis: a contributing factor in delayed carotid occlusion of a
      patient with carotid blowout syndrome treated with stent grafts.
AB  - Distal marginal stenosis is rarely reported to be a factor associated with poor
      long-term patency of patients of head and neck cancers with carotid blowout
      syndrome treated with stent grafts. We report a case of laryngeal cancer with
      rupture of the right common carotid artery. A self-expandable stent graft was
      deployed, but bleeding recurred. Another stent graft was deployed for the
      pseudoaneurysm located distal to the first stent graft. Rebleeding occurred
      because of pseudoaneurysm formation from reconstituted branches of the right
      superior thyroid artery. We performed direct percutaneous puncture of the
      proximal superior thyroid artery for successful embolization. Distal marginal
      stenosis and asymptomatic thrombosis of the carotid artery were noted at 3.5- and
      5-month follow-ups, respectively. We suggest aggressive early follow-up and
      reintervention for distal marginal stenosis by combined antibiotic therapy and
      angioplasty and stenting to improve the long-term patency of stent-graft
      deployment for management of carotid blowout syndrome.

PMID- 20685598
TI  - Concurrence of Incontinentia Pigmenti and Behcet's Disease.
AB  - We report here a rare case of incontinentia pigmenti (IP) in a 10-year-old girl
      who developed Behcet's disease. IP was diagnosed in infancy and Behcet's disease
      was diagnosed at 10 years of age. The initial presentations of Behcet's disease
      were spiking fever and recurrent painful oral and genital ulcers that were
      refractory to antibiotics. After corticosteroid treatment, her fever subsided and
      ulcers subsequently healed. The patient's mother and sister were also diagnosed
      with IP. Her mother had suffered from Behcet's disease since her teenage years
      and it was complicated with colon perforation. Although there are several reports
      on the combination of IP and Behcet's disease, this is the first reported case of
      a family with such concurrence.

PMID- 20685600
TI  - Development of an in process control filtration-assisted chemiluminometric
      immunoassay to quantify foot and mouth disease virus (FMDV) non-capsid proteins
      in vaccine-antigen batches.
AB  - In many countries, foot and mouth disease (FMD) is controlled by vaccination and
      surveillance against non-capsid proteins (NCP); therefore vaccines are required
      not to induce antibodies against NCP. Vaccine purity is evaluated by repeated
      inoculation of naive cattle, an expensive and time consuming protocol that raises
      several animal welfare concerns. We have developed an in process control
      filtration-assisted chemiluminometric immunoassay (FAL-ELISA), to detect and
      quantify NCP in vaccine-antigen batches regardless of its volume and composition.
      Samples are filtered through PVDF-filter microplates pre-coated with a monoclonal
      antibody against NCP. Filtration removes all unbound components in the sample and
      captured NCP are detected by anti-NCP conjugate followed by incubation with the
      substrate, luminol/peroxide. Analytical detection limit was 2 ng for purified NCP
      and 4 ng for vaccine-antigen batches spiked with NCP, which makes this assay
      sensitive enough to be applied to purity control of FMD vaccines. Vaccine
      components did not interfere with the antibody and substrate reactions in the
      assay. FAL-ELISA is an alternative for the in vivo tests, observing the objective
      to Replace, Reduce and Refine the use of animals for quality control of
      immunobiologicals.

PMID- 20685601
TI  - Influenza virus-like particles coated onto microneedles can elicit stimulatory
      effects on Langerhans cells in human skin.
AB  - Virus-like particles (VLPs) have a number of features that make them attractive
      influenza vaccine candidates. Microneedle (MN) devices are being developed for
      the convenient and pain-free delivery of vaccines across the skin barrier layer.
      Whilst MN-based vaccines have demonstrated proof-of-concept in mice, it is vital
      to understand how MN targeting of VLPs to the skin epidermis affects activation
      and migration of Langerhans cells (LCs) in the real human skin environment. MNs
      coated with vaccine reproducibly penetrated freshly excised human skin,
      depositing 80% of the coating within 60 s of insertion. Human skin experiments
      showed that H1 (A/PR/8/34) and H5 (A/Viet Nam/1203/04) VLPs, delivered via MN,
      stimulated LCs resulting in changes in cell morphology and a reduction in cell
      number in epidermal sheets. LC response was significantly more pronounced in skin
      treated with H1 VLPs, compared with H5 VLPs. Our data provides strong evidence
      that MN-facilitated delivery of influenza VLP vaccines initiates a stimulatory
      response in LCs in human skin. The results support and validate animal data,
      suggesting that dendritic cells (DCs) targeted through deposition of the vaccine
      in skin generate immune response. The study also demonstrates the value of using
      human skin alongside animal studies for preclinical testing of intra-dermal (ID)
      vaccines.

PMID- 20685603
TI  - CD10+ pancreatic stellate cells enhance the progression of pancreatic cancer.
AB  - BACKGROUND & AIMS: Pancreatic stellate cells (PSCs) promote the progression of
      pancreatic cancer by producing extracellular matrix and soluble factors. However,
      the functional heterogeneity of PSCs has not been identified until now. Detailed
      characterization of the PSCs in human pancreatic cancer would provide a set of
      potential targets for stroma-directed therapy. METHODS: We isolated PSCs from
      fresh pancreatic ductal adenocarcinoma tissue and sorted them by flow cytometry
      according to cell surface expression of CD10, which is a stromal prognostic
      marker for various tumors. We analyzed the functional differences between CD10(+)
      PSCs and CD10(-) PSCs. RESULTS: Immunohistochemical analysis showed that the
      frequency of CD10 expression by PSCs was markedly higher in tumor tissue than in
      normal tissue (33.7% vs 0%, respectively, P = .028). In pancreatic ductal
      adenocarcinoma, CD10 expression by PSCs was associated with positive nodal
      metastases (P = .011) and a shorter survival time (P < .001). In vitro coculture
      experiments showed that CD10(+) PSCs promoted the invasiveness of pancreatic
      cancer cell lines, SUIT-2 and Panc-1 cells more intensively than CD10(-) PSCs.
      CD10(+) PSCs significantly increased the tumor growth and invasiveness of SUIT-2
      cells in a murine cotransplantation model. CD10(+) PSCs secreted higher levels of
      matrix metalloproteinase 3 than CD10(-) PSCs, and knockdown of matrix
      metalloproteinase 3 in cocultured PSCs reduced the invasion of SUIT-2 and Panc-1
      cells. CONCLUSIONS: CD10(+) PSCs enhance the progression of pancreatic cancer
      cells. CD10(+) PSCs may be a candidate for selective therapeutic targeting in the
      treatment of pancreatic cancer.

PMID- 20685607
TI  - A mathematical and computational approach for integrating the major sources of
      cell population heterogeneity.
AB  - Several approaches have been used in the past to model heterogeneity in bacterial
      cell populations, with each approach focusing on different source(s) of
      heterogeneity. However, a holistic approach that integrates all the major sources
      into a comprehensive framework applicable to cell populations is still lacking.
      In this work we present the mathematical formulation of a cell population master
      equation (CPME) that describes cell population dynamics and takes into account
      the major sources of heterogeneity, namely stochasticity in reaction, DNA
      duplication, and division, as well as the random partitioning of species contents
      into the two daughter cells. The formulation also takes into account cell growth
      and respects the discrete nature of the molecular contents and cell numbers. We
      further develop a Monte Carlo algorithm for the simulation of the stochastic
      processes considered here. To benchmark our new framework, we first use it to
      quantify the effect of each source of heterogeneity on the intrinsic and the
      extrinsic phenotypic variability for the well-known two-promoter system used
      experimentally by Elowitz et al. (2002). We finally apply our framework to a more
      complicated system and demonstrate how the interplay between noisy gene
      expression and growth inhibition due to protein accumulation at the single cell
      level can result in complex behavior at the cell population level. The generality
      of our framework makes it suitable for studying a vast array of artificial and
      natural genetic networks. Using our Monte Carlo algorithm, cell population
      distributions can be predicted for the genetic architecture of interest, thereby
      quantifying the effect of stochasticity in intracellular reactions or the
      variability in the rate of physiological processes such as growth and division.
      Such in silico experiments can give insight into the behavior of cell populations
      and reveal the major sources contributing to cell population heterogeneity.

PMID- 20685608
TI  - Cognitive domains affected by histamine H(1)-antagonism in humans: a literature
      review.
AB  - The neurotransmitter histamine has been suggested to be involved in cognitive
      functioning. Generally, studies in animals have shown a decrease in performance
      after decreasing histamine neurotransmission and improved performance after
      increasing histamine neurotransmission. It is unclear, however, what role
      histamine plays in cognition in humans. Up until now, most data are derived from
      studies and reviews that aimed to assess the sedative potential of H(1)
      antagonists and not the effects on cognition in particular. The objective of this
      paper is specifically to review which cognitive domains are affected by H(1)
      antagonists. Taken together, 90 experimental studies on the performance effects
      of sedative H(1)-antagonists published between 1973 and 2009 were reviewed.
      Results showed that psychomotor skills and attention are most frequently impaired
      and memory the least. Tasks assessing memory that were affected usually required
      rapid responses. It was concluded that both the complexity of the task as well as
      the demand for information processing speed determines the sensitivity to the
      effects of central H(1)-antagonism. The importance of the sensitive cognitive
      domains to histaminergic dysfunction, as well as the relation between histamine
      related decrease in arousal and task performance deserve further research.

PMID- 20685609
TI  - Estrogens in rheumatoid arthritis; the immune system and bone.
AB  - Rheumatoid arthritis (RA) is an autoimmune disease that is more common in women
      than in men. The peak incidence in females coincides with menopause when the
      ovarian production of sex hormones drops markedly. RA is characterized by
      skeletal manifestations where production of pro-inflammatory mediators, connected
      to the inflammation in the joint, leads to bone loss. Animal studies have
      revealed distinct beneficial effects of estrogens on arthritis, and a positive
      effect of hormone replacement therapy has been reported in women with
      postmenopausal RA. This review will focus on the influence of female sex hormones
      in the pathogenesis and progression of RA.

PMID- 20685613
TI  - Molecular mechanisms of isocyanate induced oncogenic transformation in ovarian
      epithelial cells.
AB  - Ovarian surface epithelium is under constant physiological pressure to maintain
      its integrity. Environmental toxic exposure can contribute to degenerative
      pathologies including ovarian cancer. Based on our current understanding, we
      aimed at listing mechanistic insights that contribute to ovarian carcinogenesis
      after exposure to methyl isocyanate, an ubiquitous environmental pollutant.
      Ovarian epithelial cells manifested a persistent DNA damage response along with
      increased accumulation of GADD45, p21, p16(INK4A) and pRb proteins upon
      treatment. Increase in cell size and beta-gal positive staining showing inception
      of premature senescence with morphological transformation and structural and
      numerical chromosomal abnormalities were also observed. Immuno-FISH analysis
      illustrated early loss of TRF2 protein suggestive of telomeric dysfunction due to
      premature senescence and plausible association with chromosomal and
      microsatellite instability. Soft-agar assay displayed neoplasticity in treated
      cells demonstrating onset of malignant transformation. These results indicate
      that isocyanate exposure alters ovarian epithelial cell proliferation and might
      lead to ovarian dysfunction and carcinogenesis.

PMID- 20685614
TI  - Co-administration of darunavir and a new pharmacokinetic booster: formulation
      strategies and evaluation in dogs.
AB  - Various formulations for combination of the anti-HIV protease inhibitor darunavir
      (DRV) and TMC41629, a pharmacokinetic booster for DRV, were studied. TMC41629 (a
      BCS-IV compound) was formulated in capsules, as polyethylene glycol 400 (PEG400)
      solution, binary or ternary self-microemulsifying drug delivery system (SMEDDS),
      inclusion complex with hydroxypropyl-beta-cyclodextrin (HPbetaCD) or
      polyvinylpyrrolidone-co-vinylacetate 64 (PVP/VA64) extrudate. In addition,
      tablets were prepared using unmilled or micronized powder and a disintegrant. On
      co-administration with DRV tablets in dogs, DRV plasma concentration levels were
      boosted by TMC41629, the PVP/VA64 extrudate achieving the highest DRV levels (2
      fold increase). Yet, with extrudate prepared with both compounds, no boosting
      effect was observed, likely due to transition of DRV from crystalline solvate to
      amorphous state. Therefore, a co-formulation, combining DRV as crystalline
      solvate with amorphous TMC41629, was developed. DRV/kappa-carrageenan 80/20%
      (w/w) beads coated with TMC41629 released at least 80% within 1h in 0.01M HCl
      with 0.5% sodium lauryl sulphate, TMC41629 dissolving faster than DRV. In dogs,
      the DRV exposure increased 2.7-fold with the TMC41629-coated beads relative to
      DRV alone, yet remained lower, but less variable, than following co
      administration as separate formulations. Coating of TMC41629 on DRV/kappa
      carrageenan beads is a suitable technique for co-formulation, whereby TMC41629
      can function as a booster of DRV.

PMID- 20685615
TI  - The G protein-coupled receptors in the silkworm, Bombyx mori.
AB  - G protein-coupled receptors (GPCRs) are the largest and most versatile family of
      transmembrane receptors in the cell, occupying the highest hierarchical positions
      in the regulation of many physiological processes. Although they have been
      extensively studied in a number of model insects, there have been few
      investigations of GPCRs in large Lepidopterans, such as Bombyx mori, an organism
      that provides a means to perform detailed tissue expression analyses, which may
      help to characterize GPCRs and their ligands. In addition, B. mori, also known as
      the silkworm, is an insect of substantial economic importance, due to its use in
      silk production and traditional medicines. In this work, we computationally
      identified 90 putative GPCRs in B. mori, 33 of which represent novel proteins.
      These GPCRs were annotated and compared with their homologs in Drosophila
      melanogaster and Anopheles gambiae. Phylogenetics analyses of the GPCRs from
      these three insects showed that GPCRs may easily duplicate or disappear during
      insect evolution, especially in the neuropeptide and protein hormone receptor
      subfamily. Interestingly, we observed a decrease in the quantity and diversity of
      the stress-tolerance gene, Methuselah, in B. mori, which may be related to its
      long history of domestication. Moreover, the presence of many Bombyx-specific
      GPCRs suggests that neither Drosophila nor Anopheles is good representatives for
      the GPCRs in the Class Insecta.

PMID- 20685616
TI  - Acaricide resistance mechanisms in the two-spotted spider mite Tetranychus
      urticae and other important Acari: a review.
AB  - The two-spotted spider mite Tetranychus urticae Koch is one of the economically
      most important pests in a wide range of outdoor and protected crops worldwide.
      Its control has been and still is largely based on the use of insecticides and
      acaricides. However, due to its short life cycle, abundant progeny and
      arrhenotokous reproduction, it is able to develop resistance to these compounds
      very rapidly. As a consequence, it has the dubious reputation to be the"most
      resistant species" in terms of the total number of pesticides to which
      populations have become resistant, and its control has become problematic in many
      areas worldwide. Insecticide and acaricide resistance has also been reported in
      the ectoparasite Sarcoptes scabiei, the causative organism of scabies, and other
      economically important Acari, such as the Southern cattle tick Rhipicephalus
      microplus, one of the biggest arthropod threats to livestock, and the parasitic
      mite Varroa destructor, a major economic burden for beekeepers worldwide.
      Although resistance research in Acari has not kept pace with that in insects, a
      number of studies on the molecular mechanisms responsible for the resistant
      phenotype has been conducted recently. In this review, state-of-the-art
      information on T. urticae resistance, supplemented with data on other important
      Acari has been brought together. Considerable attention is given to the
      underlying resistance mechanisms that have been elucidated at the molecular
      level. The incidence of bifenazate resistance in T. urticae is expanded as an
      insecticide resistance evolutionary paradigm in arthropods.

PMID- 20685618
TI  - Exposure to sublethal concentration of glyphosate or atrazine-based herbicides
      alters the phagocytic function and increases the susceptibility of silver catfish
      fingerlings (Rhamdia quelen) to Aeromonas hydrophila challenge.
AB  - The resistance of fish to microorganisms challenge depends mainly on the efficacy
      of the immune response. Most studies on the natural immune response of fish have
      focused on the effect of diets and immunostimulants. Few studies correlated the
      presence of commonly used agrichemical and susceptibility to infection by aquatic
      microorganism. Thus, this study aimed to investigate the effect of glyphosate and
      atrazine-based herbicides on immune cell phagocytosis and susceptibility of
      silver catfish to Aeromonas hydrophila infection. Following exposure to sublethal
      concentrations of glyphosate or atrazine (10% of the LC(50-96 h)), a significant
      decrease in the number of intracelomatic cells and phagocytic index could be
      observed. In addition, silver catfish fingerlings exposed to glyphosate or
      atrazine were more susceptible to intracelomatic challenge with pathogenic A.
      hydrophila. Thus, the presence of these herbicides on the water alters the
      natural immune response to bacterial and possibly to other aquatic microorganism.

PMID- 20685617
TI  - Dynamic fluorescence depolarization: a powerful tool to explore protein folding
      on the ribosome.
AB  - Protein folding is a fundamental biological process of great significance for
      cell function and life-related processes. Surprisingly, very little is presently
      known about how proteins fold in vivo. The influence of the cellular environment
      is of paramount importance, as molecular chaperones, the ribosome, and the
      crowded medium affect both folding pathways and potentially even equilibrium
      structures. Studying protein folding in physiologically relevant environments,
      however, poses a number of technical challenges due to slow tumbling rates, low
      concentrations and potentially non-homogenous populations. Early work in this
      area relied on biological assays based on antibody recognition, proteolysis, and
      activity studies. More recently, it has been possible to directly observe the
      structure and dynamics of nascent polypeptides at high resolution by
      spectroscopic and microscopic techniques. The fluorescence depolarization decay
      of nascent polypeptides labeled with a small extrinsic fluorophore is a
      particularly powerful tool to gain insights into the dynamics of newly
      synthesized proteins. The fluorophore label senses both its own local mobility
      and the motions of the macromolecule to which it is attached. Fluorescence
      anisotropy decays can be measured both in the time and frequency domains. The
      latter mode of data collection is extremely convenient to capture the nanosecond
      motions in ribosome-bound nascent proteins, indicative of the development of
      independent structure and folding on the ribosome. In this review, we discuss the
      theory of fluorescence depolarization and its exciting applications to the study
      of the dynamics of nascent proteins in the cellular environment.

PMID- 20685622
TI  - Cryoablation versus radiofrequency ablation for treatment of atrioventricular
      nodal reentrant tachycardia.

PMID- 20685623
TI  - Cytochromes P450 in nanodiscs.
AB  - Nanodiscs have proven to be a versatile tool for the study all types of membrane
      proteins, including receptors, transporters, enzymes and viral antigens. The self
      assembled Nanodisc system provides a robust and common means for rendering these
      targets soluble in aqueous media while providing a native like bilayer
      environment that maintains functional activity. This system has thus provided a
      means for studying the extensive collection of membrane bound cytochromes P450
      with the same biochemical and biophysical tools that have been previously limited
      to use with the soluble P450s. These include a plethora of spectroscopic, kinetic
      and surface based methods. Significant improvements in homogeneity and stability
      of these preparations open new possibilities for detailed analysis of equilibrium
      and steady-state kinetic characteristics of catalytic mechanisms of human
      cytochromes P450 involved in xenobiotic metabolism and in steroid biosynthesis.
      The experimental methods developed for physico-chemical and functional studies of
      membrane cytochromes P450 incorporated in Nanodiscs allow for more detailed
      understanding of the scientific questions along the lines pioneered by Professor
      Klaus Ruckpaul and his array of colleagues and collaborators.

PMID- 20685624
TI  - The pharmacokinetics and pharmacodynamics of the carbapanemes: focus on
      doripenem.
AB  - Carbapenems are the most potent group of beta-lactam agents, having a broad
      spectrum of bactericidal activity against both Gram-negative and Gram-positive
      bacteria including anaerobes. Doripenem is a new carbapenem endowed with
      excellent bactericidal activity, a wide spectrum of antibacterial activity
      against difficult nosocomial pathogens, including extended-spectrum beta
      lactamase producers. Its high stability in solution render it extremely flexible
      for dosing and infusion time. It is the only carbapenem which has been registered
      officially for administration as an extended infusion of more than 4 hours, which
      can thus enhance its potential clinical efficacy against difficult bacterial
      pathogens with MICs of 4-8 mg/L.

PMID- 20685625
TI  - Therapeutic management of bacterial meningitis in children: a systematic review
      and comparison of published guidelines from a European perspective.
AB  - Bacterial meningitis is an infectious disease emergency that can cause
      substantial morbidity and mortality. We compared the most recent international
      guidelines and recommendations on bacterial meningitis management in infants and
      children in developed countries, in terms of initial management approach,
      empirical antimicrobial therapy, timing, dosages, and duration of antimicrobial
      therapy, and possible adjunctive treatment with dexamethasone. Secondly,
      epidemiological data on bacterial resistance in several european countries were
      analyzed and discussed in relation to the therapies currently recommended for
      bacterial meningitis. The comparative analysis of the selected guidelines
      highlighted significant differences in the therapeutic management of bacterial
      meningitis. Differences among guidelines have important consequences for daily
      practice. An agreed protocol for early, evidence-based, and effective therapeutic
      management of bacterial meningitis is essential for the best outcome. further
      studies and expert consensus are required to establish the best management of
      bacterial meningitis in the european setting based on the most recent
      epidemiological data on resistance rates.

PMID- 20685619
TI  - Searching for immunomodulatory sequences in sea bass (Dicentrarchus labrax L.):
      transcripts analysis from thymus.
AB  - The thymus is a key organ of the immune system in most vertebrates and, for this
      reason, it has been used in this paper for the generation of a normalized cDNA
      library from sea bass (Dicentrarchus labrax), one of the most extensively
      cultured species in South Mediterranean aquaculture. A total of 1632 ESTs from
      this library were initially analysed for sequence quality and vector sequences
      and, after this control, 1264 (77% of total clones sequenced) high-quality ESTs
      were further processed. The total collection of D. labrax thymus ESTs has been
      deposited in the EBI-GenBank-DBJ database (GenBank accession numbers from
      FN565576 to FN566839). The functional classification of ESTs was performed by
      Gene Ontology and KEGG annotation and, successively, the sequences were analysed
      using the ImmunomeBase software to identify potentially immuno-related genes.
      Using this approach, we found about 100 putative genes involved in immune system
      responses, most new in sea bass, that were analysed more in detail. Some of the
      potentially interesting genes identified by these in silico analyses were studied
      by real-time PCR to verify their expression both at basal level and after in
      vitro stimulation of sea bass head kidney leukocytes. The used strategy has been
      confirmed as a good approach to discover new immuno-related genes and to improve
      the knowledge of specific markers that could help the discrimination of T-cell
      subpopulations in sea bass and, in general, in Teleosts.

PMID- 20685626
TI  - Pharmacodynamics of moxifloxacin versus vancomycin against biofilms of
      methicillin-resistant Staphylococcus aureus and epidermidis in an in vitro model.
AB  - The aim of this study was to compare the activities of moxifloxacin and
      vancomycin against methicillin-resistant Staphylococcus aureus (MRSA) and
      methicillin-resistant Staphylococcus epidermidis (MRSE) biofilms. The study was
      conducted using a novel in vitro pharmacodynamic model where the biofilms were
      treated with a simulated clinical dosing of vancomycin 1 g every 12 h or
      moxifloxacin 400 mg every 24 h. Vancomycin failed to produce a 2 log reduction in
      the biofilm embedded bacterial count against either of the tested organisms at
      any time. Moxifloxacin treatment, on the other hand, exhibited a superior anti
      biofilm activity and resulted in a 2.5- and 3.7-log reduction in the MRSA and
      MRSE bacterial bioburdens, respectively, after 24 h of exposure. the results
      support the implementation of further in vivo and clinical studies aimed at
      demonstrating the efficacy of moxifloxacin in the treatment of MRSA and MRSE
      biofilm-associated infections.

PMID- 20685627
TI  - QnrB9 in association with TEM-116 extended-spectrum beta-lactamase in Citrobacter
      freundii isolated from sewage effluent: first report from Italy.
AB  - The aim of the present study was to investigate the mechanism of quinolone and
      beta-lactam resistance in an isolate of Citrobacter freundii PC2/08 collected
      from sewage effluent from l'Aquila, Italy. QnrB-9 and bla(TEM-116 )were co
      expressed in a large plasmid identified in C. freundi PC2/08 strain. Compared to
      TEM-1, TEM-116 showed two single mutations: V84I and A184V. The plPC2/08 plasmid
      conferred resistance to several beta-lactams and fluoroquinolones. Tazobactam
      could be considered a good inhibitor whereas clavulanic acid was unable to
      restore susceptibility to amoxicillin. The QnrB-9 element seems to confer the
      same level of resistance to levofloxacin and ciprofloxacin with minimum
      inhibitory concentration (MIC) values of 4 mg/l for either. In this study, we
      confirm the common association of plasmid-mediated quinolone resistance with
      extended-spectrum beta-lactamase (ESbetaL) production. This is the first finding
      in Italy of qnrB9 and TEM-116 in a non-clinical or animal strain.

PMID- 20685628
TI  - Quantitative differences in antibiotic resistance between methicillin-resistant
      and methicillin-susceptible Staphylococcus aureus strains isolated in Hungary,
      Austria and Macedonia.
AB  - The aim of this study was to compare the quantitative susceptibility of
      methicillin-resistant and -susceptible Staphylococcus aureus (MRSA and MSSA)
      strains from three European countries to nine antistaphylococcal agents. The
      antibiotic susceptibility of 274 MRSA and 284 MSSA strains from Hungary, Austria
      and macedonia was tested by the broth microdilution method. The clonal
      relationship of strains was determined by pulsed-field gel electrophoresis.
      Intermediate susceptibility to vancomycin appeared in Macedonian MRSA strains.
      Macedonian MRSA strains had high-level amikacin and gentamicin resistance. MSSA
      strains generally were susceptible to all drugs at minimum inhibitory
      concentrations (MIC(50)) except for gentamicin resistance in Macedonian strains.
      In Hungary and Austria a common antibiotic resistance phenotype of MRSA
      predominated, while in macedonia three other phenotypes were also prevalent.
      Geographical differences in the resistance of S. aureus are still high. Since
      resistance levels of MRSA and MSSA strains differ extensively, they should be
      considered separately for antibiotic resistance analysis.

PMID- 20685629
TI  - National surveillance of antimicrobial susceptibility of CTX-M-positive and 
      negative clinical isolates of Escherichia coli from Kuwait government hospitals.
AB  - Antibiotic resistance in Escherichia coli is becoming a complex therapeutic
      problem. Surveillance programs are valuable tools and offer important information
      on bacterial resistance trends. This study was undertaken to determine the
      susceptibility of clinically significant isolates of E. coli obtained from
      patients admitted to 8 Kuwait government hospitals and to examine how this was
      influenced by the production of CTX-M extended-spectrum beta-lactamases (ESBLs).
      The susceptibility of 876 consecutive clinically significant strains of E. coli
      to 13 antibiotics was determined by Etest. ESBL production was assessed by ESBL
      Etest method and the presence of CTX-M beta-lactamases was confirmed by PCR
      technique. Of the 876 isolates, 604 (69%) were highly non-susceptible to
      ampicillin with MIC(90 )of >256 microg/ml. Resistance to the 3(rd)-generation
      cephalosporins ranged from 7.5% in the Maternity hospital to 29% in the Ibn Sina
      hospital; ciprofloxacin resistance rates ranged from 14% and 40%, respectively.
      Carbapenems and amikacin demonstrated excellent activity. The minimum inhibitory
      concentrations (MIC(90)) of cefotaxime, ceftazidime, cefepime and ciprofloxacin
      were >256, 64, >256 and >32 microg/ml, respectively for CTX-M-positive isolates
      versus 0.5, 1, 025 and 0.125 microg/ml for CTX-M-negative strains. Frequencies of
      CTX-M-positive isolates within the cefotaxime MIC ranges of 1-2, 3-8, 9-16 and
      >16 microg/ml were 0, 4, 15 and 81%, respectively. In conclusion, the
      susceptibility of E. coli to the 3(rd )generation cephalosporins and
      ciprofloxacin was influenced by the presence of CTX-M ESBL and a high proportion
      of the CTX-M-producing isolates were in the susceptibility ranges of cefotaxime.

PMID- 20685630
TI  - In vitro selection of ertapenem and piperacillin/tazobactam-resistant strains of
      Bacteroides fragilis and analysis of their virulence in gnotobiotic mice.
AB  - Ertapenem and piperacillin/tazobactam are beta-lactam antibiotics with a broad
      spectrum of activity, used for the treatment of mixed infections, in which
      Bacteroides fragilis plays an important etiological role. The aim of this study
      was to select strains of B. fragilis resistant to these drugs and correlate the
      phenotype profiles of these lineages with changes in the virulence of the
      original bacterium. B. fragilis ATCC 25285, sensitive to the drugs listed, was
      used in this study. Strains resistant to these drugs were obtained by multi-step
      method and this condition was confirmed by comparing the time-kill curve of the
      original strain with those curves obtained from derived-resistant strains. To
      assess the virulence, germ-free mice were challenged intragastrically with the
      original strain or those derived-resistant. The mouse infection by the
      piperacillin/tazobactam-resistant B. fragilis strain produced increased levels of
      C-reactive protein, alkaline phosphatase and white blood cells and reduced
      platelet counts, what may indicate that acquisition of piperacillin/tazobactam
      resistance may enhance the pathogenic properties of these B. fragilis strains.

PMID- 20685631
TI  - Clinical efficacy of moxifloxacin versus comparator therapies for community
      acquired pneumonia caused by Legionella spp.
AB  - The aim of this study was to compare outcomes for patients with community
      acquired pneumonia (CAP) caused by Legionella spp. following treatment with
      moxifloxacin or a range of comparator antimicrobial agents. Data were pooled from
      four sequential I.V./P.O. trials of moxifloxacin in the treatment of CAP.
      Comparators were ceftriaxone +/- erythromycin, amoxicillin/clavulanate +/-
      clarithromycin, trovafloxacin, levofloxacin, or ceftriaxone + levofloxacin.
      Legionella infection was diagnosed by culture, urine antigen testing and/or
      serology. Clinical success rates for the efficacy-valid (per protocol)
      populations were recorded at the test-of-cure visit (5-30 days post-therapy).
      Severity of CAP was determined using the modified American Thoracic Society
      criteria.Of 1786 efficacy-valid patients, 33 (1.8%) had documented infection with
      Legionella spp. (moxifloxacin: n=13; comparator: n=20). Of these, 30 cases were
      identified by serology and/or urine antigen detection and 3 by respiratory
      culture. The success rate of moxifloxacin vs. comparator therapy was 92.3% vs.
      80.0% for the I.V./P.O. trials.Sequential (I.V./P.O.) moxifloxacin demonstrated
      clinical efficacy that was at least as good as that of comparator treatments for
      the treatment of CAP due to Legionella.

PMID- 20685632
TI  - Use of intravenous co-trimoxazole to treat bacterial infection: analysis of 50
      treatment episodes.
AB  - Co-trimoxazole is infrequently prescribed in the UK due to concerns regarding
      adverse events. However, it has a low association with Clostridium difficile
      associated disease (CDAD) and may represent an alternative to higher-risk agents.
      This retrospective study examines the efficacy and safety of intravenous co
      trimoxazole in treatment of bacterial infection in a UK inpatient population of
      50 inpatients. Outcome was determined to be successful in 58% of treatment
      episodes; in hospital-acquired pneumonia the response rate was 52%. Two treatment
      episodes were terminated due to adverse events: these resolved on discontinuation
      of co-trimoxazole. No significant change in renal function, evaluated by serum
      creatinine, was observed during therapy; blood platelet count was not affected by
      treatment with intravenous co-trimoxazole. One patient developed CDAD within one
      month of cessation of therapy. Intravenous co-trimoxazole was clinically
      effective with a low rate of adverse events and may represent a useful
      alternative antimicrobial agent in UK institutions with high rates of CDAD.

PMID- 20685633
TI  - Correlation of extreme drug resistant assay results and progression-free survival
      following intraperitoneal chemotherapy for advanced ovarian cancer.
AB  - The aim of this study was to determine if in vitro extreme drug resistance (EDR)
      to platinum and/or taxane chemotherapy was predictive of patient response to
      intraperitoneal (I.P.) chemotherapy in patients with stage III or recurrent
      epithelial ovarian cancer (EOC). Fifty-six patients were retrospectively
      identified who underwent optimal cytoreductive surgery for primary or recurrent
      eOC and then received at least three cycles of either intravenous (I.V.) or I.P.
      chemotherapy with platinum and paclitaxel-based chemotherapy. EDR to platinum
      and/or paclitaxel was determined using a commercially available assay (Oncotech,
      Inc., Tustin, CA). The primary outcome measure was progression-free survival
      (PFS). Twenty-nine (52%) patients received I.P. chemotherapy and 27 (48%)
      received I.V. chemotherapy. The patients were well matched in terms of age,
      stage, grade and histology. Ten (35%) patients in the I.OP. arm and ten (37%)
      patients in the I.V. arm showed EDR to either platinum and/or paclitaxel. Median
      PFS for all I.P. chemotherapy patients was 23 months, compared with 13 months for
      those receiving I.V. chemotherapy (p = 0.04). Patients with EDR to platinum
      and/or taxane who underwent I.V. chemotherapy had a median PFS of 13.5 months,
      whereas those who underwent I.P. treatment had a median PFS of 15 months (p =
      0.69). Median overall survival had not been reached at the time of analysis.No
      significant difference in PFS was noted between patients who underwent I.P. and
      those who underwent I.V. chemotherapy when EDR was predicted to either platinum
      or paclitaxel or both. These data suggest that the decision to offer I.P.
      chemotherapy, with the attendant increase in morbidity, in the setting of EDR to
      platinum and/or taxane chemotherapy, may not be beneficial. Prospective studies,
      preferably analyzing platinum or taxane EDR individually, are required to
      validate these observations.

PMID- 20685634
TI  - Low dose fractionated cisplatin plus gemcitabine for elderly patients with
      advanced non small cell lung cancer: a retrospective analysis.
AB  - The aim of the study was to evaluate safety and efficacy of gemcitabine-cisplatin
      in elderly patients with advanced non small cell lung cancer (NSCLC). This study
      included 59 patients aged >70 years consecutively admitted to our Department.
      treatment consisted of gemcitabine 1000 mg/m(2) on days 1 and 8, and low-dose
      fractionated cisplatin 20 mg/m(2) on days 1, 2, 3 of a 21-day cycle. Toxicity was
      graded according to the world Health Organization (WHO) criteria.A total of 281
      cycles was administered. Hematological toxicities of grade 3 and 4 were seen in
      17% and 5% of patients, respectively. Grade 3 gastrointestinal toxicity was 3%,
      grade 2 neuropathy was 2%. Twenty-nine partial responses with an objective
      response rate of 49% were obtained. No complete responses were observed. The
      median progression-free survival (PFS) and overall survival (OS) were 7.8 and
      15.5 months respectively. Cisplatin-based combination chemotherapy at low doses
      appears to be safe and active in older patients with advanced NSCLC.

PMID- 20685635
TI  - Are disk diffusion and Etest methods reliable for detecting Candida glabrata and
      other species' susceptibility to fluconazole and voriconazole?

PMID- 20685636
TI  - Generation of mutants in Candida albicans with reduced susceptibility to
      caspofungin: influence on other antifungal products.

PMID- 20685637
TI  - Impact of the administration of liposomal amphotericin B in patients with renal
      function impairment at initiation of treatment.

PMID- 20685638
TI  - [Tuberculosis control programme in Tunisia: efficacy assessment].
AB  - The aim of this study was to assess the efficacy of the national Tuberculosis
      Control Programme in Tunisia, by applying the 8-stage model proposed by Piot
      (1967). Two retrospective cohorts of tuberculosis cases, including all new smear
      positive cases detected by all laboratories in the study area during the study
      period, were selected at least 2 years after treatment began. The real number of
      new active cases during the study period was estimated at 142, the case detection
      rate at 61%. In all, 70% of patients started tuberculosis treatment, and regular
      use of the home treatment varied from 87% (including irregular use) to 71%
      (excluding irregular use). The low global efficacy of the program, which ranged
      from 26 to 31%, indicates the need for improved application of the strategy by
      programme managers.

PMID- 20685639
TI  - Ferris Smith technique for full-thickness oral commissure defect.

PMID- 20685640
TI  - [Malaria transmission in lagoon areas in Cote d'Ivoire: the villages of N'gatty
      and Allaba].
AB  - The ecological and climatic variations in tropical areas of Africa make the
      transmission of malaria very heterogeneous. Several species of mosquitoes of the
      Anopheles genus transmit the disease. In Cote d'Ivoire, studies in the southern
      and northern forests have shown the involvement of Anopheles gambiae, An.
      funestus and An. nili in this transmission. This study was conducted in N'gatty
      and Allaba, two villages in a lagoon area of southern Cote d'Ivoire, in the
      district of Dabou. The district is located between 05 degrees 18 N and 04 degrees
      27 W, about 40 kilometres from the economic capital of Cote d'Ivoire, and has a
      surface of 2257.8 km2. Two lagoon villages, N'gatty and Allaba, about a kilometre
      apart, were selected as sites for this research. The topography of N'gatty is
      rugged, with two important sides: a banana plantation on the west and the lagoon
      on the east, covered by aquatic plants (Pistia stratiotes, Acrosticum aureum,
      nympheacae and Eichhornia crassipes). This aquatic vegetation separates the last
      plots of the village from the lagoon. Mosquito populations were sampled from
      December 2007 through September 2008 by nighttime captures on volunteers three
      consecutive nights each month, inside six living rooms (4 in N'gatty and 2 in
      Allaba, a smaller village). The mosquitoes were captured when they landed on the
      volunteer's legs. There were two teams of catchers for each home; the first
      worked from 18:00 h to 24:00 and the second from 24:00 to 06:00. The ovaries and
      glands of An. gambiae were dissected. The physiological age of the females was
      determined by the appearance of the trachea on ovarian dissection. The
      sporozoites were sought by optic microscopy in cooled glands in a drop of
      physiological salt solution. During the 10 months of this study, 21 137
      mosquitoes were caught in N'gatty and 7163 in Allaba. An. gambiae species
      accounted for less than 2% of the mosquito fauna in the two villages. Overall,
      the average bite rate was 203.24 bites per man per night (b/m/n) in N'gatty and
      137.75 in Allaba. The average number of An. gambiae bites was 4.04 b/m/n in
      N'gatty and 2 b/m/n in Allaba. Annually, the average An. gambiae bites totalled
      1474.6 bites per man per year (b/m/y) in N'gatty and 730 in Allaba. No An.
      funestus mosquito was caught in Allaba, and its average number of bites per man
      per year in N'gatty was only 3.65. No infected glands (n = 420 dissected) were
      found in N'gatty throughout the investigation. The mean sporozoite rate in Allaba
      was only 0.285% (n = 104). The mean entomological inoculation rate (EIR) was
      estimated at 0.017 infecting bites per man and per night (ib/m/n) in N'Gatty and
      6.2 in Allaba. This weak entomological inoculation rate leads us to consider
      continuing the research for infection of An. gambiae by ELISA techniques. In
      conclusion, malaria transmission by An. gambiae in this area is very low.

PMID- 20685641
TI  - [Rare localisations of endemic Burkitt lymphoma: about 21 cases observed in the
      Haematology Department of the University Hospital of Yopougon Abidjan].
AB  - In this retrospective study, we analysed rare localisations of Burkitt lymphoma
      observed in the Haematology Department of the University Hospital of Yopougon
      Abidjan. Over a 10-year study period, we saw 106 patients with Burkitt lymphoma,
      21 with unusual localisations. The mean age at onset of symptoms or discovery was
      15.48 years, and more patients were female. There were 8 cases of primary Burkitt
      lymphoma in a rare localisation and 13 cases of unusual localisations of
      secondary lymphomas. The most frequent of these rare lesions were renal (6),
      ovarian (4), in peripheral nodes (4), testicular (3), and mammary (3). Still
      rarer were thyroid, skin, pulmonary, and suprarenal localisations. Clinical
      manifestations were non-specific and difficult to differentiate from other solid
      tumours. The CMA protocol produced complete remission in 29% of cases (n=6).
      Seven patients died. In conclusion, the rare forms of Burkitt lymphoma are non
      specific and can be mistaken for other solid tumours. Diagnosis should thus be
      based on histochemical analysis.

PMID- 20685642
TI  - [Management of postpartum vaginal haematomas by embolisation: two cases].
AB  - Postpartum vaginal haematomas are a rare complication of delivery. The incidence
      of large haematomas is estimated at 1/4000 deliveries, and this complication can
      be life-threatening. We report two such cases. The diagnosis is suggested by
      shooting perineal pain with urinary tenesmus and vulvovaginal swelling or an
      unexplained haemorrhagic syndrome in the postpartum period. Rapid management is
      essential. Embolisation by interventional radiology is preferred to surgery. In
      the first case, arterial embolisation was performed after bilateral ligation of
      the hypogastric arteries failed. Arterial embolisation was the first-line
      treatment for the second patient. It was successful for both women.

PMID- 20685643
TI  - [Community organizations and fighting STDs, HIV and AIDS in Montreal: lessons for
      sub-Saharan Africa].
AB  - The HIV/AIDS pandemic is one of the most important public health problems in the
      world. In Benin as elsewhere in Africa, the combination of some sociological and
      sociocultural factors with socio-economic realities have led this pandemic to
      progress faster in some farming regions than in urban areas. This survey was
      performed during a three-month internship researching community-based
      organizations in Montreal that care for HIV/AIDS patients. OBJECTIVES: to analyse
      the actions taken by community-based organisations to combat this pandemic and
      point out the strengths and weaknesses of this system; - to draw useful lessons
      to apply in Africa. METHOD: more than one hundred organisations play a direct or
      indirect role in the combat against HIV/AIDS in the city ofMontreal. The choice
      of organisations to visit was determined by their interest for HIV/AIDS
      prevention and treatment or for the struggle against social exclusion. After a
      visit and guided tour of the premises of each organisation, one of its officials
      was interviewed for 20 to 30 minutes (according to a semi-structured outline,
      appendix 2. The data were analysed manually. RESULTS: the survey showed that even
      in high-income countries, the same risk behaviors, equally influenced by poverty,
      social exclusion andvulnerability, lead to this disease. Further, its chronic
      nature, related to essentially permanent antiretroviral treatments makes it
      harder for vulnerable groups to maintain healthy behaviours. The concentration of
      disease in vulnerable groups gives a false sense of security to most of the
      population, which does not feel concerned, ignores messages intended to raise
      awareness, and does not participate in voluntary screening. The organisations and
      actors involved, with the support of public health facilities, battle this
      vulnerability while providing information and resources to the target groups to
      help them protect themselves better. This struggle thus remains too focused on
      these target groups. Efforts must be made to make the discourse on AIDS legible
      to broader populations, for the borderlines between these target groups and the
      rest of the population is very fuzzy. Discussion and lessons: This analysis of
      the process of fighting HIV/AIDS inMontreal identified some positive experiences
      that can inspire concrete actions in African setting. One is the experience of
      the Farha Foundation, an organisation specialized in community fund-raising,
      which puts its collections at the disposal of other community organisations, and
      is independent, receiving no funding from local, provincial or federal public
      authorities. Transposition of this experience to Africa would require
      contextualisation and would need to mobilize the resources of not only the local
      community but also the national and international communities. The "Ruban en
      route" organization provides useful awareness programs for the young, visiting
      primary and secondary schools to debate HIV/AIDS issues with students with games,
      and demonstrating condom use. In the African context, given the limited
      educational system and the extent of school quitting, such an organisation would
      need to find a means to reach young apprentices and young farmers in informal
      structures. Action Sero Zero and Stella target male homosexuals and sex workers,
      respectively, and work to have their rights recognized by the community. The
      application of their policies would not be possible in our societies, for
      sociocultural reasons. Instead efforts must be directed toward making the
      community understand the need to encourage and tolerate recognition and aid for
      prostitutes, for the good of all. To a lesser degree, the experience of "Spectre
      de rue" with the TAPAJ project (Travail Alternatif Paye A la Journee or
      alternative work paid daily) is also importable, although only in urban
      environments where "street kids" are an important phenomenon. In some cities,
      where their number is increasing, this activity can be connected to an
      organisation working on awareness campaigns among the young. Contact with these
      street children should help them to become more socialized and to find the means
      to earn their living more legally. Finally, the usefulness of providing anti
      retroviral treatment to people living with HIV is the most important lesson we
      learned during our Montreal stay. This very useful experience will nonetheless be
      very difficult to undertake in a rural African environment. Indeed, making
      antiretroviral cocktails available to patients might risk consuming the quasi
      totality of the budget available for prevention. Work on this aspect is possible
      only if the local, national and international community mobilizes to provide the
      resources necessary. The international community is, however, starting to do so,
      by means of the Global Fund, to fight malaria, HIV/AIDS and tuberculosis. This
      survey has thus allowed us to learn some useful means of combatting AIDS in
      Africa.

PMID- 20685644
TI  - A multidimensional view of personal health systems for underserved populations.
AB  - The advent of electronic personal health records (PHR) provides a major
      opportunity to encourage positive health management practices, such as chronic
      disease management. Yet, to date there has been little attention toward the use
      of PHRs where advanced health information services are perhaps most needed,
      namely, in underserved communities. Drawing upon research conducted with safety
      net providers and patients, the authors propose a multi-level analytical
      framework for guiding actions aimed at fostering PHR adoption and utilization.
      The authors first outline distinctive user and technical requirements that need
      to be considered. Next, they assess organizational requirements necessary to
      implement PHRs within health systems bound by limited resources. Finally, the
      authors analyze the overriding health care policy context that can facilitate or
      thwart such efforts. The conclusion notes that heightened national attention
      toward health information technology and reform provides a significant
      opportunity for initiatives whose goal is to increase widepread access to PHRs.

PMID- 20685645
TI  - Clinical simulation in maternity (CSiM): interprofessional learning through
      simulation team training.
AB  - BACKGROUND: Focusing on interprofessional relations in team performance to
      improve patient safety is an emerging priority in obstetrics. A review of the
      literature found little information on roles and teamwork in obstetric emergency
      training. Qualitative research was undertaken through a Clinical Simulation in
      Maternity programme which gives interprofessional rural clinicians the
      opportunity to learn collaboratively through simulated obstetric emergencies.
      This research aimed to determine how interprofessional simulation team training
      improved maternity emergency care and team performance. METHOD: This research
      used thematic inductive analysis using data from in-depth interviews. In total 17
      participants and four facilitators who took part in the Clinical Simulation in
      Maternity workshops were invited to participate in an interview 1-2 weeks
      postworkshop and then again 3-6 months later. Data were deidentified then coded
      manually and with the assistance of computer program NVivo 7 (QSR International).
      FINDINGS: Of the major themes identified, Collaboration in Teambuilding was
      separated into four subthemes (Personal Role Awareness, Interpositional
      Knowledge, Mutuality and Leadership). CONCLUSION: This research highlights the
      significance of interprofessional training, particularly through simulation
      learning in a team where rural clinicians are able to learn more about each other
      and gain role clarity, leadership skills and mutuality in a safe environment.

PMID- 20685646
TI  - Crystal structures of Bacillus cereus NCTU2 chitinase complexes with
      chitooligomers reveal novel substrate binding for catalysis: a chitinase without
      chitin binding and insertion domains.
AB  - Chitinases hydrolyze chitin, an insoluble linear polymer of N-acetyl-d
      glucosamine (NAG)(n), into nutrient sources. Bacillus cereus NCTU2 chitinase
      (ChiNCTU2) predominantly produces chitobioses and belongs to glycoside hydrolase
      family 18. The crystal structure of wild-type ChiNCTU2 comprises only a catalytic
      domain, unlike other chitinases that are equipped with additional chitin binding
      and insertion domains to bind substrates into the active site. Lacking chitin
      binding and chitin insertion domains, ChiNCTU2 utilizes two dynamic loops (Gly-67
      Thr-69 and Ile-106-Val-112) to interact with (NAG)(n), generating novel substrate
      binding and distortion for catalysis. Gln-109 is crucial for direct binding with
      substrates, leading to conformational changes of two loops with a maximum shift
      of ~4.6 A along the binding cleft. The structures of E145Q, E145Q/Y227F, and
      E145G/Y227F mutants complexed with (NAG)(n) reveal (NAG)(2), (NAG)(2), and
      (NAG)(4) in the active site, respectively, implying various stages of reaction:
      before hydrolysis, E145G/Y227F with (NAG)(4); in an intermediate state,
      E145Q/Y227F with a boat-form NAG at the -1 subsite, -1-(NAG); after hydrolysis,
      E145Q with a chair form -1-(NAG). Several residues were confirmed to play
      catalytic roles: Glu-145 in cleavage of the glycosidic bond between -1-(NAG) and
      +1-(NAG); Tyr-227 in the conformational change of -1-(NAG); Asp-143 and Gln-225
      in stabilizing the conformation of -1-(NAG). Additionally, Glu-190 acts in the
      process of product release, and Tyr-193 coordinates with water for catalysis.
      Residues Asp-143, E145Q, Glu-190, and Tyr-193 exhibit multiple conformations for
      functions. The inhibitors zinc ions and cyclo-(l-His-l-Pro) are located at
      various positions and confirm the catalytic-site topology. Together with kinetics
      analyses of related mutants, the structures of ChiNCTU2 and its mutant complexes
      with (NAG)(n) provide new insights into its substrate binding and the mechanistic
      action.

PMID- 20685647
TI  - Role of histidine 932 of the human mitochondrial DNA polymerase in nucleotide
      discrimination and inherited disease.
AB  - The human mitochondrial DNA polymerase (pol gamma) is nuclearly encoded and is
      solely responsible for the replication and repair of the mitochondrial genome.
      The progressive accumulation of mutations within the mitochondrial genome is
      thought to be related to aging, and mutations in the pol gamma gene are
      responsible for numerous heritable disorders including progressive external
      opthalmoplegia, Alpers syndrome, and parkinsonism. Here we investigate the
      kinetic effect of H932Y, a mutation associated with opthalmoplegia. Mutations
      H932Y and H932A reduce the specificity constant governing correct nucleotide
      incorporation 150- and 70-fold, respectively, without significantly affecting
      fidelity of incorporation or the maximum rate of incorporation. However, this
      leads to only a 2-fold reduction in rate of incorporation at a physiological
      nucleotide concentration (~100 MUm). Surprisingly, incorporation of T:T or C:T
      mismatches catalyzed by either H932Y or H932A mutants was followed by slow
      pyrophosphate release (or fast pyrophosphate rebinding). Also, H932Y readily
      catalyzed incorporation of multiple mismatches, which may have a profound
      physiological impact over time. His-932 is thought to contact the beta-phosphate
      of the incoming nucleotide, so it is perhaps surprising that H932Y appears to
      slow rather than accelerate pyrophosphate release.

PMID- 20685648
TI  - A specific docking site for DNA polymerase {alpha}-primase on the SV40 helicase
      is required for viral primosome activity, but helicase activity is dispensable.
AB  - Replication of simian virus 40 (SV40) DNA, a model for eukaryotic chromosomal
      replication, can be reconstituted in vitro using the viral helicase (large tumor
      antigen, or Tag) and purified human proteins. Tag interacts physically with two
      cellular proteins, replication protein A and DNA polymerase alpha-primase (pol
      prim), constituting the viral primosome. Like the well characterized primosomes
      of phages T7 and T4, this trio of proteins coordinates parental DNA unwinding
      with primer synthesis to initiate the leading strand at the viral origin and each
      Okazaki fragment on the lagging strand template. We recently determined the
      structure of a previously unrecognized pol-prim domain (p68N) that docks on Tag,
      identified the p68N surface that contacts Tag, and demonstrated its vital role in
      primosome function. Here, we identify the p68N-docking site on Tag by using
      structure-guided mutagenesis of the Tag helicase surface. A charge reverse
      substitution in Tag disrupted both p68N-binding and primosome activity but did
      not affect docking with other pol-prim subunits. Unexpectedly, the substitution
      also disrupted Tag ATPase and helicase activity, suggesting a potential link
      between p68N docking and ATPase activity. To assess this possibility, we examined
      the primosome activity of Tag with a single residue substitution in the Walker B
      motif. Although this substitution abolished ATPase and helicase activity as
      expected, it did not reduce pol-prim docking on Tag or primosome activity on
      single-stranded DNA, indicating that Tag ATPase is dispensable for primosome
      activity in vitro.

PMID- 20685649
TI  - Cytoplasmic accumulation of the RNA-binding protein HuR stabilizes the ornithine
      decarboxylase transcript in a murine nonmelanoma skin cancer model.
AB  - Ornithine decarboxylase (ODC) is the first and usually rate-limiting enzyme in
      the polyamine biosynthetic pathway. Under normal physiological conditions,
      polyamine content and ODC enzyme activity are highly regulated. However, the
      induction of ODC activity is an early step in neoplastic transformation. The
      studies described here use normal mouse keratinocytes (C5N cells), and spindle
      carcinoma cells (A5 cells) to explore the regulation of ODC in nonmelanoma skin
      cancer development. Previous results have shown that induction of ODC activity is
      both necessary and sufficient for the promotion of skin tumors. We see a marked
      increase in ODC enzyme activity in A5 cells compared with C5N keratinocytes,
      which correlates with a 4-fold stabilization of ODC mRNA. These data suggest that
      ODC is post-transcriptionally regulated in skin tumor development. Thus, we
      sought to investigate whether the ODC transcript interacts with the RNA-binding
      protein HuR, which is known to bind to and stabilize its target mRNAs. We show
      that HuR is able to bind to the ODC 3'-UTR in A5 cells but not in C5N cells.
      Immunofluorescence results reveal that HuR is present in both the nucleus and
      cytoplasm of A5 cells, whereas C5N cells exhibit strictly nuclear localization of
      HuR. Knockdown experiments in A5 cells showed that when HuR is depleted, ODC RNA
      becomes less stable, and ODC enzyme activity decreases. Together, these data
      support the hypothesis that HuR plays a causative role in ODC up-regulation
      during nonmelanoma skin cancer development by binding to and stabilizing the ODC
      transcript.

PMID- 20685650
TI  - Identification of a novel marker for dendritic cell maturation, mouse
      transmembrane protein 123.
AB  - Dendritic cells (DCs) are a group of professional antigen-presenting cells, and
      many genes are known to be associated with their maturation. We compared the
      transcriptional profiles of immature and mature mouse Langerhans cells using the
      suppressive, subtractive hybridization method and identified a novel gene of
      unknown function, termed herein transmembrane protein 123 (Tmem123), of which
      mRNA expression was enhanced in mature but not in immature Langerhans cells. Its
      expression was also enhanced in other mature DCs such as bone marrow-derived DCs
      (BMDCs) and splenic DCs. Interestingly, CD40 expression was up-regulated on
      mature BMDCs cultured with colchicine concurrently with the enhanced expression
      of Tmem123 compared with that of fresh BMDCs. Furthermore, the expression of CD40
      was enhanced on Tmem123-transfected DC2.4 cells, a mouse BMDC-derived cell line,
      compared with that on mock-transfected DC2.4 cells. This enhancement of CD40
      expression did not occur after deletion of lysosome/endosome targeting YXXphi
      motifs (where X is any amino acid and phi is a bulky hydrophobic amino acid) in
      the Tmem123 cytoplasmic tail. By stimulation with anti-CD40 monoclonal antibody,
      these transfectants secreted an increased amount of IL-12/23 p40 compared with
      mock-transfected DC2.4 cells. Thus, our study demonstrates that Tmem123 may be
      used as a new maturation marker in DCs and that this molecule may be closely
      associated with the cell surface expression of CD40.

PMID- 20685651
TI  - Ras homolog enriched in brain (Rheb) enhances apoptotic signaling.
AB  - Rheb is a homolog of Ras GTPase that regulates cell growth, proliferation, and
      regeneration via mammalian target of rapamycin (mTOR). Because of the well
      established potential of activated Ras to promote survival, we sought to
      investigate the ability of Rheb signaling to phenocopy Ras. We found that
      overexpression of lipid-anchored Rheb enhanced the apoptotic effects induced by
      UV light, TNFalpha, or tunicamycin in an mTOR complex 1 (mTORC1)-dependent
      manner. Knocking down endogenous Rheb or applying rapamycin led to partial
      protection, identifying Rheb as a mediator of cell death. Ras and c-Raf kinase
      opposed the apoptotic effects induced by UV light or TNFalpha but did not prevent
      Rheb-mediated apoptosis. To gain structural insight into the signaling
      mechanisms, we determined the structure of Rheb-GDP by NMR. The complex adopts
      the typical canonical fold of RasGTPases and displays the characteristic GDP
      dependent picosecond to nanosecond backbone dynamics of the switch I and switch
      II regions. NMR revealed Ras effector-like binding of activated Rheb to the c-Raf
      Ras-binding domain (RBD), but the affinity was 1000-fold lower than the Ras/RBD
      interaction, suggesting a lack of functional interaction. shRNA-mediated
      knockdown of apoptosis signal-regulating kinase 1 (ASK-1) strongly reduced UV or
      TNFalpha-induced apoptosis and suppressed enhancement by Rheb overexpression. In
      conclusion, Rheb-mTOR activation not only promotes normal cell growth but also
      enhances apoptosis in response to diverse toxic stimuli via an ASK-1-mediated
      mechanism. Pharmacological regulation of the Rheb/mTORC1 pathway using rapamycin
      should take the presence of cellular stress into consideration, as this may have
      clinical implications.

PMID- 20685652
TI  - Sumoylation and nuclear translocation of S100A4 regulate IL-1beta-mediated
      production of matrix metalloproteinase-13.
AB  - S100A4, a member of the S100 family of proteins, plays an important role in
      matrix remodeling by up-regulating the expression of matrix metalloproteinases
      (MMPs). We have previously shown that S100A4 is overexpressed in diseased
      cartilage and that extracellular S100A4 stimulates MMP-13 production, a major
      type II collagen-degrading enzyme, via activation of receptor for advanced
      glycation end product signaling. In the present study, using human articular
      chondrocytes, we show that intracellular S100A4 translocated into the nucleus
      upon interleukin-1beta (IL-1beta) stimulation and translocation required post
      translational modification of S100A4 by the sumo-1 protein. Two sumoylation sites
      were identified on the S100A4 molecule, Lys(22) and Lys(96). Mutation of these
      lysine residues abolished the ability of S100A4 to be sumoylated and to
      translocate into the nucleus. Blocking of sumoylation and nuclear transport of
      S100A4 inhibited the IL-1beta-induced production of MMP-13. Nuclear S100A4 was
      bound to the promoter region of MMP-13 in IL-1beta-treated cells. Thus, we
      demonstrate a novel mechanism for sumoylated S100A4 as a regulator of expression
      of the MMP-13 gene.

PMID- 20685653
TI  - Coordination between cell cycle progression and cell fate decision by the p53 and
      E2F1 pathways in response to DNA damage.
AB  - After DNA damage, cells must decide between different fates including growth
      arrest, DNA repair, and apoptosis. Both p53 and E2F1 are transcription factors
      involved in the decision process. However, the mechanism for cross-talk between
      the p53 and E2F1 pathways still remains unclear. Here, we proposed a four-module
      kinetic model of the decision process and explored the interplay between these
      two pathways in response to ionizing radiation via computer simulation. In our
      model the levels of p53 and E2F1 separately exhibit pulsatile and switching
      behaviors. Upon DNA damage, p53 is first activated, whereas E2F1 is inactivated,
      leading to cell cycle arrest in the G(1) phase. We found that the ultimate
      decision between cell life and death is determined by the number of p53 pulses
      depending on the extent of DNA damage. For repairable DNA damage, the cell can
      survive and reenter the S phase because of the activation of E2F1 and
      inactivation of p53. For irreparable DNA damage, growth arrest is overcome by
      growth factors, and activated p53 and E2F1 cooperate to initiate apoptosis. We
      showed that E2F1 promotes apoptosis by up-regulating the proapoptotic cofactors
      of p53 and procaspases. It was also revealed that deregulated E2F1 by oncogene
      activation can make cells sensitive to DNA damage even in low serum medium. Our
      model consistently recapitulates the experimental observations of the intricate
      relationship between p53 and E2F1 in the DNA damage response. This work
      underscores the significance of E2F1 in p53-mediated cell fate decision and may
      provide clues to cancer therapy.

PMID- 20685654
TI  - Hyaluronan synthesis mediates the fibrotic response of keratocytes to
      transforming growth factor beta.
AB  - TGFbeta induces fibrosis in healing corneal wounds, and in vitro corneal
      keratocytes up-regulate expression of several fibrosis-related genes in response
      to TGFbeta. Hyaluronan (HA) accumulates in healing corneas, and HA synthesis is
      induced by TGFbeta by up-regulation of HA synthase 2. This study tested the
      hypothesis that HA acts as an extracellular messenger, enhancing specific
      fibrotic responses of keratocytes to TGFbeta. HA synthesis inhibitor 4
      methylumbelliferone (4MU) blocked TGFbeta induction of HA synthesis in a
      concentration-dependent manner. 4MU also inhibited TGFbeta-induced up-regulation
      of alpha-smooth muscle actin, collagen type III, and extra domain A-fibronectin.
      Chemical analogs of 4MU also inhibited fibrogenic responses in proportion to
      their inhibition of HA synthesis. 4MU, however, showed no effect on TGFbeta
      induction of luciferase by the 3TP-Lux reporter plasmid. Inhibition of HA using
      siRNA to HA synthase 2 reduced TGFbeta up-regulation of smooth muscle actin,
      fibronectin, and cell division. Similarly, brief treatment of keratocytes with
      hyaluronidase reduced TGFbeta responses. These results suggest that newly
      synthesized cell-associated HA acts as an extracellular enhancer of wound healing
      and fibrosis in keratocytes by augmenting a limited subset of the cellular
      responses to TGFbeta.

PMID- 20685655
TI  - Insulin represses transcription of the thyroid stimulating hormone beta-subunit
      gene through increased recruitment of nuclear factor I.
AB  - Although the regulation of thyroid stimulating hormone beta-subunit gene
      (TSHbeta) has been intensively studied, the functions of transcription factors
      involved are not fully understood. The authors found that the -615/-516 promoter
      region of the TSHbeta interacts specifically with nuclear proteins derived from
      pituitary tissue or from cultured thyrotroph cells. The actual binding site at
      the nucleotide level, as revealed by DNase I protection assay, includes the
      consensus sequence for nuclear factor I (NFI). RT-PCR analysis indicated that NFI
      B expression is restricted to thyrotroph cells in the anterior pituitary. EMSA
      and ChIP analysis showed that NFI-B binds most efficiently to the -588/-560
      region of TSHbeta promoter. The forced expressions of NFI-B markedly reduced
      TSHbeta promoter activity and its mRNA expression. Furthermore, it was also shown
      that the -588/-560 region is involved in the insulin-mediated repression of the
      TSHbeta. It was of particular interest to observe that NFI-B was recruited to the
      -588/-560 region of the TSHbeta promoter in an insulin-dependent manner. Taken
      together, this study provides new insights of the delicate regulations of energy
      metabolism and hormonal homeostasis.

PMID- 20685656
TI  - SIRT4 regulates fatty acid oxidation and mitochondrial gene expression in liver
      and muscle cells.
AB  - SIRT4, a member of the sirtuin family, has been implicated in the regulation of
      insulin secretion by modulation of glutamate dehydrogenase. However, the role of
      this enzyme in the regulation of metabolism in other tissues is unknown. In this
      study we investigated whether depletion of SIRT4 would enhance liver and muscle
      metabolic functions. To do this SIRT4 was knocked down using an adenoviral shRNA
      in mouse primary hepatocytes and myotubes. We observed a significant increase in
      gene expression of mitochondrial and fatty acid metabolism enzymes in hepatocytes
      with reduced SIRT4 levels. SIRT4 knockdown also increased SIRT1 mRNA and protein
      levels both in vitro and in vivo. In agreement with the increased fatty acid
      oxidation (FAO) gene expression, we showed a significant increase in FAO in SIRT4
      knockdown primary hepatocytes compared with control, and this effect was
      dependent on SIRT1. In primary myotubes, knockdown of SIRT4 resulted in increased
      FAO, cellular respiration, and pAMPK levels. When SIRT4 was knocked down in vivo
      by tail vein injection of a shRNA adenovirus, we observed a significant increase
      in hepatic mitochondrial and FAO gene expression consistent with the findings in
      primary hepatocytes. Taken together these findings demonstrate that SIRT4
      inhibition increases fat oxidative capacity in liver and mitochondrial function
      in muscle, which might provide therapeutic benefits for diseases associated with
      ectopic lipid storage such as type 2 diabetes.

PMID- 20685657
TI  - Interferon-gamma-mediated inhibition of serum response factor-dependent smooth
      muscle-specific gene expression.
AB  - IFNgamma exerts multiple biological effects on effector cells by regulating many
      downstream genes, including smooth muscle-specific genes. However, the molecular
      mechanisms underlying IFNgamma-induced inhibition of smooth muscle-specific gene
      expression remain unclear. In this study, we have shown that serum response
      factor (SRF), a common transcriptional factor important in cell proliferation,
      migration, and differentiation, is targeted by IFNgamma in a STAT1-dependent
      manner. We show that the molecular mechanism by which IFNgamma regulates SRF is
      via activation of the 2-5A-RNase L system, which triggers SRF mRNA decay and
      reduced SRF expression. As a result, decreased SRF expression reduces expression
      of SRF target genes such as smooth muscle alpha-actin and smooth muscle myosin
      heavy chain. Additionally, IFNgamma reduced p300 and acetylated histone-3 binding
      in both smooth muscle alpha-actin and SRF promoters, epigenetically decreasing
      smooth muscle alpha-actin and SRF transcriptional activation. Our data reveal
      that SRF is a novel IFNgamma-regulated gene and further elucidate the molecular
      pathway between IFNgamma, IFNgamma-regulated genes, and SRF and its target genes.

PMID- 20685658
TI  - Crystallographic studies of prion protein (PrP) segments suggest how structural
      changes encoded by polymorphism at residue 129 modulate susceptibility to human
      prion disease.
AB  - A single nucleotide polymorphism (SNP) in codon 129 of the human prion gene,
      leading to a change from methionine to valine at residue 129 of prion protein
      (PrP), has been shown to be a determinant in the susceptibility to prion disease.
      However, the molecular basis of this effect remains unexplained. In the current
      study, we determined crystal structures of prion segments having either Met or
      Val at residue 129. These 6-residue segments of PrP centered on residue 129 are
      "steric zippers," pairs of interacting beta-sheets. Both structures of these
      "homozygous steric zippers" reveal direct intermolecular interactions between Met
      or Val in one sheet and the identical residue in the mating sheet. These two
      structures, plus a structure-based model of the heterozygous Met-Val steric
      zipper, suggest an explanation for the previously observed effects of this locus
      on prion disease susceptibility and progression.

PMID- 20685659
TI  - Serine- and arginine-rich proteins 55 and 75 (SRp55 and SRp75) induce production
      of HIV-1 vpr mRNA by inhibiting the 5'-splice site of exon 3.
AB  - HIV-1 non-coding exon 3 can either be spliced to exons 4, 4a, 4b, 4c, and 5 to
      generate tat, rev, and nef mRNAs or remain unspliced to produce the 13a7 vpr
      mRNA. Here we show that serine- and arginine-rich proteins 55 and 75 (SRp55 and
      SRp75) inhibit splicing from the 5'-splice site of exon 3 thereby causing an
      accumulation of the partially unspliced 13a7 vpr mRNA. In contrast, serine- and
      arginine-rich protein 40 (SRp40) induces splicing from exon 3 to exon 4, thereby
      promoting the production of the 1347 tat mRNA. We demonstrate that SRp55
      stimulates vpr mRNA production by interacting with the previously identified HIV
      1 splicing enhancer named GAR and inhibiting its function. This inhibition
      requires both serine arginine-rich and RNA-binding domains of SRp55, indicating
      that production of HIV-1 vpr mRNA depends on the interaction of SRp55 with an
      unknown factor.

PMID- 20685661
TI  - Coronary artery disease risk factors in urban areas of Yazd City, Iran.
AB  - BACKGROUND: Coronary artery disease (CAD) is a major cause of mortality and
      morbidity with high health care cost in both developed and developing countries.
      CAD accounts for nearly 50% of all yearly deaths in Iran. OBJECTIVE: The aim of
      this study is to explore the main CAD risk factors in the urban areas of Yazd in
      the Islamic Republic of Iran. METHODS: A hospital-based case-control study was
      conducted to investigate the role of the important CAD risk factors in urban area
      of Yazd city from December 2007 to June 2008. A total of 436 subjects in the age
      group of 30 to 75 years (218 cases and 218 controls) were included in this study.
      The tools of enquiry were a pretested and precoded questionnaire, physical
      examination, and laboratory findings. A confidence level of 95% and study power
      of 80% were considered for the interpretation of possible significant findings.
      Gender-wise stratified analysis was separately done for men and women using
      multiple conditional logistic regression. RESULTS: A total of 75.5% of the
      participants were men and 24.5% were women. Five variables, including unskilled
      jobs, physical inactivity, giving positive history of hypertension, high levels
      of waist/hip ratio, and low levels of high-density lipoprotein (HDL) were the
      factors that could account for significant predictors of CAD in males on the
      logistic model (P < .05). No such significant CAD predictors were found for
      women. CONCLUSION: The findings showed that categories of nonprofessional,
      physical inactivity, positive history of hypertension, wais/hip ratio >=0.9 and
      HDL levels <=40 mg/dL are the significant risk factors that can predict CAD in
      male residents of Yazd.

PMID- 20685660
TI  - Structural and functional analyses of a conserved hydrophobic pocket of
      flavivirus methyltransferase.
AB  - The flavivirus methyltransferase (MTase) sequentially methylates the N7 and 2'-O
      positions of the viral RNA cap (GpppA-RNA -> m(7)GpppA-RNA -> m(7)GpppAm-RNA),
      using S-adenosyl-l-methionine (AdoMet) as a methyl donor. We report here that
      sinefungin (SIN), an AdoMet analog, inhibits several flaviviruses through
      suppression of viral MTase. The crystal structure of West Nile virus MTase in
      complex with SIN inhibitor at 2.0-A resolution revealed a flavivirus-conserved
      hydrophobic pocket located next to the AdoMet-binding site. The pocket is
      functionally critical in the viral replication and cap methylations. In addition,
      the N7 methylation efficiency was found to correlate with the viral replication
      ability. Thus, SIN analogs with modifications that interact with the hydrophobic
      pocket are potential specific inhibitors of flavivirus MTase.

PMID- 20685662
TI  - Closing the international health gaps: Taiwan comes in from the cold.
AB  - A revised set of International Health Regulations came into force in June 2007. A
      month earlier, The Lancet had noted the importance of filling the remaining gaps
      in the global health system. One of these gaps was the exclusion of Taiwan from
      the structures of the World Health Organization (WHO), denied a presence at the
      World Health Assembly and able to communicate with the WHO only through a complex
      and time-consuming bureaucratic process. This situation was becoming increasingly
      indefensible in the face of clear difficulties in transmitting information about
      epidemic diseases, such as the SARS outbreak in 2003 and the growing threat of
      avian influenza since 2004. This is at last being addressed following a landmark
      decision to admit Taiwan to observer status at the World Health Assembly in May
      2009. These developments will be addressed in this article.

PMID- 20685663
TI  - Perceived health status and daily activity participation of older Malaysians.
AB  - This article investigates the influence of perceived health status on the daily
      activity participation of older Malaysians. Data from the Survey on Perceptions
      of Needs and Problems of the Elderly, which was conducted in 1999, were used. The
      negative binomial regression results show that older persons with good perceived
      health status reported more varieties of daily activity participation, especially
      among the uneducated and those with below-average self-esteem. The multinomial
      logistic regression model suggests that older persons with good perceived health
      status tended to engage daily in paid work only or with leisure activities,
      whereas those perceived to have poor health were more likely to engage in leisure
      activities only or leisure and family role activities. Promotion of a healthy
      lifestyle at a younger age encourages every person to monitor and take
      responsibility for their own health, which is a necessary strategy to ensure
      active participation at an older age, and thus improve their well-being.

PMID- 20685664
TI  - Healthy life expectancy in the context of population health and ageing in India.
AB  - This study examines life expectancy (LE) and healthy life expectancy (HLE) in
      India longitudinally over the period 2007 to 2020, providing projections into the
      future. Specifically, the Indian Healthy Life Expectancy Projection model was
      developed based on epidemiological data (mortality, disability rates) obtained
      from the World Health Organization and the Government of India. The current model
      contributed to 4 key findings: decreases in mortality but not in all age and
      gender groups; increasing disability in the Indian population over time; increase
      in LE and HLE into the future in all age and gender groups; and the largest gains
      in LE and HLE are in the older age bands starting from the 70+ age band in women
      and 65+ age band in men. This study sheds some light on the population health
      measures needed to improve the understanding of the determinants of health for
      the efficient allocation of resources and to inform policy in the planning of
      health and social services.

PMID- 20685665
TI  - Joint prevalence and control of hypercholesterolemia and hypertension in
      Thailand: third national health examination survey.
AB  - The prevalence, diagnosis, treatment, and control of hypercholesterolemia and/or
      hypertension were estimated for Thailand using data from a recent, nationally
      representative health examination survey. Multivariate logistic regression was
      used to assess factors associated with diagnosis, treatment, and control. In all,
      14% of men and 17% of women had hypercholesterolemia, 23% and 21% had
      hypertension, and 5% and 6%, respectively, had both. A large proportion of
      individuals with these risk factors is neither diagnosed nor treated, let alone
      adequately controlled; 30% of people with hypertension had been diagnosed and 24%
      treated, and 9% had their blood pressure controlled. The figures for
      hypercholesterolemia were 13%, 9%, and 6%, respectively. Those for both risk
      factors combined were below 15% and did not differ by sex, urbanicity, age, or
      marital status. Among men, education correlated with diagnosis and treatment
      odds. There is great scope for improved prevention of cardiovascular disease in
      Thailand.

PMID- 20685666
TI  - Controlling influenza A (H1N1) in China: Bayesian or frequentist approach.
AB  - This article discusses two approaches to controlling the newly identified
      influenza A (H1N1): via Bayesian and frequentist statistical reasoning. This
      study reviewed the measures implemented in China as an example to illustrate
      these two approaches. Since May 2009, China has deployed strict controlling
      mechanisms based on the strong prior Bayesian assumption that the origin of
      influenza A (H1N1) was from outside China and as such strict border control would
      keep the virus from entering China. After more than 4 months of hard work by
      Chinese health professionals and officials, the number of confirmed influenza A
      (H1N1) has increased steadily against the expectations of the general public.
      Taking into account the great financial burden in maintaining strict measures,
      Chinese health authorities have slowly adjusted their policies of controlling
      influenza A (H1N1) in China according to frequentist reasoning since July 2009.

PMID- 20685667
TI  - Sociodemographic factors associated with aggressive driving behaviors of 3
      wheeler taxi drivers in Sri Lanka.
AB  - Little is known about the nature and scope of aggressive driving in developing
      countries. The objective of this study is to specifically examine the
      sociodemographic factors associated with aggressive driving behavior among 3
      wheeler taxi drivers in Sri Lanka. Convenience samples of 3-wheeler taxi drivers
      from Rathnapura, Ahaliyagoda, Sri Lanka were surveyed from June to August 2006.
      Analyses included bivariate and multivariate logistic regression. Drivers with
      less than high school education were 3.5 times more likely to drive aggressively
      (odds ratio [OR] = 3.46; 95% confidence interval [CI] = 1.08, 11.1). Single
      drivers were 9 times more likely to run red lights (OR = 8.74; 95% CI = 2.18,
      35.0), and being single was a major risk factor for drunk driving (OR = 4.80; 95%
      CI = 1.23, 18.7). Furthermore, high school completers were 4 times more likely to
      bribe a policeman (OR = 4.27; 95% CI = 1.23, 14.9) when caught violating the road
      rules. Aggressive driving and risk-taking behavior are amenable to policy
      initiatives, and preventive programs targeted at key groups could be used to
      improve road safety in Sri Lanka. This study demonstrates that aggressive driving
      behavior is associated with sociodemographic factors, including the level of
      education, marital status, and other socioeconomic factors. Hence, economic
      factors should be addressed to find solutions to traffic-related issues. It will
      be the government's and policy makers' responsibility to try and understand the
      economic factors behind risky road behavior and bribe-taking behavior prior to
      legislating or enforcing new laws.

PMID- 20685668
TI  - Germline APC mutation spectrum derived from 863 genomic variations identified
      through a 15-year medical genetics service to French patients with FAP.
AB  - Heterozygous APC germline alteration is responsible for familial adenomatous
      polyposis, a colon cancer predisposition with almost complete penetrance. Point
      mutations generally lead to truncated proteins or no protein at all. They mainly
      involve exon 3 to codon 1700 (exon 15). The work presented here delineates
      precisely the APC mutation spectrum from 15 years of systematic molecular
      screening which identified 863 independent alterations in the French population.

PMID- 20685669
TI  - Epigenotype-phenotype correlations in Silver-Russell syndrome.
AB  - BACKGROUND: Silver-Russell syndrome (SRS) is characterised by intrauterine growth
      restriction, poor postnatal growth, relative macrocephaly, triangular face and
      asymmetry. Maternal uniparental disomy (mUPD) of chromosome 7 and hypomethylation
      of the imprinting control region (ICR) 1 on chromosome 11p15 are found in 5-10%
      and up to 60% of patients with SRS, respectively. As many features are non
      specific, diagnosis of SRS remains difficult. Studies of patients in whom the
      molecular diagnosis is confirmed therefore provide valuable clinical information
      on the condition. METHODS: A detailed, prospective study of 64 patients with
      mUPD7 (n=20) or ICR1 hypomethylation (n=44) was undertaken. RESULTS AND
      CONCLUSIONS: The considerable overlap in clinical phenotype makes it difficult to
      distinguish these two molecular subgroups reliably. ICR1 hypomethylation was more
      likely to be scored as 'classical' SRS. Asymmetry, fifth finger clinodactyly and
      congenital anomalies were more commonly seen with ICR1 hypomethylation, whereas
      learning difficulties and referral for speech therapy were more likely with
      mUPD7. Myoclonus-dystonia has been reported previously in one mUPD7 patient. The
      authors report mild movement disorders in three further cases. No correlation was
      found between clinical severity and level of ICR1 hypomethylation. Use of
      assisted reproductive technology in association with ICR1 hypomethylation seems
      increased compared with the general population. ICR1 hypomethylation was also
      observed in affected siblings, although recurrence risk remains low in the
      majority of cases. Overall, a wide range of severity was observed, particularly
      with ICR1 hypomethylation. A low threshold for investigation of patients with
      features suggestive, but not typical, of SRS is therefore recommended.

PMID- 20685670
TI  - Parthenogenetic chimaerism/mosaicism with a Silver-Russell syndrome-like
      phenotype.
AB  - INTRODUCTION: We report a 34-year-old Japanese female with a Silver-Russell
      syndrome (SRS)-like phenotype and a mosaic Turner syndrome karyotype
      (45,X/46,XX). METHODS/RESULTS: Molecular studies including methylation analysis
      of 17 differentially methylated regions (DMRs) on the autosomes and the XIST-DMR
      on the X chromosome and genome-wide microsatellite analysis for 96 autosomal loci
      and 30 X chromosomal loci revealed that the 46,XX cell lineage was accompanied by
      maternal uniparental isodisomy for all chromosomes (upid(AC)mat), whereas the
      45,X cell lineage was associated with biparentally derived autosomes and a
      maternally derived X chromosome. The frequency of the 46,XX upid(AC)mat cells was
      calculated as 84% in leukocytes, 56% in salivary cells, and 18% in buccal
      epithelial cells. DISCUSSION: The results imply that a parthenogenetic activation
      took place around the time of fertilisation of a sperm missing a sex chromosome,
      resulting in the generation of the upid(AC)mat 46,XX cell lineage by
      endoreplication of one blastomere containing a female pronucleus and the 45,X
      cell lineage by union of male and female pronuclei. It is likely that the extent
      of overall (epi)genetic aberrations exceeded the threshold level for the
      development of SRS phenotype, but not for the occurrence of other imprinting
      disorders or recessive Mendelian disorders.

PMID- 20685671
TI  - The GST domain of GDAP1 is a frequent target of mutations in the dominant form of
      axonal Charcot Marie Tooth type 2K.
AB  - BACKGROUND: Mutations in GDAP1 associate with demyelinating (CMT4A) and axonal
      (CMT2K) forms of CMT. While CMT4A shows recessive inheritance, CMT2K can present
      with either recessive (AR-CMT2K) or dominant segregation pattern (AD-CMT2K), the
      latter being characterised by milder phenotypes and later onset. The majority of
      the GDAP1 mutations are associated with CMT4A and AR-CMT2K, with only four
      heterozygous mutations identified in AD-CMT2K. METHODS: We screened GDAP1 gene in
      a series of 43 index patients, 39 with CMT2 and 4 with intermediate CMT, with
      sporadic and familial occurrence of the disease. RESULTS: Three novel mutations
      were identified in three families with dominant segregation of the disease: two
      missense changes, p.Arg226Ser and p.Ser34Cys, affecting the GST domain of the
      GDAP1 protein and a novel deletion (c.23delAG) leading to early truncation of the
      protein upstream the GST domain. Wide variability in clinical presentation is
      shared by all three families mostly in terms of age at onset and disease
      severity. A rare variant p.Gly269Arg, located within the GST domain, apparently
      acts as phenotype modulator in the family carrying the deletion. CONCLUSION: The
      results obtained reveal a GDAP1 mutation frequency of 27% in the dominant
      families analysed, a figure still unreported for this gene, thus suggesting that
      GDAP1 involvement in dominant CMT2 might be higher than expected.

PMID- 20685672
TI  - ABCC8 and KCNJ11 molecular spectrum of 109 patients with diazoxide-unresponsive
      congenital hyperinsulinism.
AB  - BACKGROUND: Congenital hyperinsulinism (CHI) is characterised by an over
      secretion of insulin by the pancreatic beta-cells. This condition is mostly
      caused by mutations in ABCC8 or KCNJ11 genes encoding the SUR1 and KIR6.2
      subunits of the ATP-sensitive potassium (K(ATP)) channel. CHI patients are
      classified according to their responsiveness to diazoxide and to their
      histopathological diagnosis (either focal, diffuse or atypical forms). Here, we
      raise the benefits/limits of the genetic diagnosis in the clinical management of
      CHI patients. METHODS: ABCC8/KCNJ11 mutational spectrum was established in 109
      diazoxide-unresponsive CHI patients for whom an appropriate clinical management
      is essential to prevent brain damage. Relationships between genotype and
      radiopathological diagnosis were analysed. RESULTS: ABCC8 or KCNJ11 defects were
      found in 82% of the CHI cases. All patients with a focal form were associated
      with a single K(ATP) channel molecular event. In contrast, patients with diffuse
      forms were genetically more heterogeneous: 47% were associated with recessively
      inherited mutations, 34% carried a single heterozygous mutation and 19% had no
      mutation. There appeared to be a predominance of paternally inherited mutations
      in patients diagnosed with a diffuse form and carrying a sole K(ATP) channel
      mutation. CONCLUSIONS: The identification of recessively inherited mutations
      related to severe and diffuse forms of CHI provides an informative genetic
      diagnosis and allows prenatal diagnosis. In contrast, in patients carrying a
      single K(ATP) channel mutation, genetic analysis should be confronted with the
      PET imaging to categorise patients as focal or diffuse forms in order to get the
      appropriate therapeutic management.

PMID- 20685673
TI  - Developmental delay and connective tissue disorder in four patients sharing a
      common microdeletion at 6q13-14.
AB  - Interstitial deletions of the long arm of chromosome 6 are rare, and most
      reported cases represent large, cytogenetically detectable deletions. The
      implementation of array comparative genome hybridisation in the diagnostic work
      up of patients presenting with congenital disorders, including developmental
      delay, has enabled identification of many patients with smaller chromosomal
      imbalances. In this report, the cases are presented of four patients with a de
      novo interstitial deletion of chromosome 6q13-14, resulting in a common
      microdeletion of 3.7 Mb. All presented with developmental delay, mild dysmorphism
      and signs of lax connective tissue. Interestingly, the common deleted region
      harbours 16 genes, of which COL12A1 is a good candidate for the connective tissue
      pathology.

PMID- 20685674
TI  - Ameliorating effects of anti-Dll4 mAb on Theiler's murine encephalomyelitis virus
      induced demyelinating disease.
AB  - We examined the role of Notch ligand Delta-like 4 (Dll4) in the development of
      Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease
      (TMEV-IDD). Treatment with mAb to Dll4, especially during the effector phase,
      resulted in significant suppression of the disease development both clinically
      and histologically. The number of infiltrating mononuclear inflammatory cells in
      the spinal cords was also decreased in mice treated with anti-Dll4 mAb. Semi
      quantitative analysis of mRNA by using real-time PCR revealed that mRNAs of T(h)1
      derived cytokines such as IFN-gamma and T(h)17-derived cytokines such as IL-17
      were decreased in mice treated with anti-Dll4 mAb, whereas those of T(h)2-derived
      cytokines such as IL-4 and IL-10 were not. Flow cytometric analysis of cytokines
      indicated that there were no significant differences between mAb-treated mice and
      control mice in the relative frequency of splenic T(h)1 and T(h)2. However,
      absolute cell numbers of T(h)1-derived cytokine-producing cells in spinal cord
      were markedly decreased in mice treated with anti-Dll4 mAb in effector phase
      compared with control mice treated with non-specific IgG. These data suggest that
      Dll4 is critically involved in the pathogenesis of TMEV-IDD and that antibodies
      to Dll4 could be used as a novel therapeutic treatment of demyelinating diseases
      such as human multiple sclerosis.

PMID- 20685675
TI  - Atrial fibrillation and mortality: the impact of antithrombotic therapy.

PMID- 20685676
TI  - Mortality predictors and effects of antithrombotic therapies in atrial
      fibrillation: insights from ACTIVE-W.
AB  - AIMS: To assess the risk of death after the occurrence of different types of non
      fatal events in patients with atrial fibrillation (AF). Antithrombotic therapies
      in AF have primarily focused on stroke prevention and bleeding. However, strokes
      and bleeds differ in severity, and the level of severity may differently impact
      mortality. METHODS AND RESULTS: We analysed the risk of subsequent mortality
      after the occurrence of non-fatal vascular and bleeding events in the Atrial
      Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events
      (ACTIVE)-W trial. In the 3371 patients randomized to vitamin K antagonists and
      the 3335 patients randomized to clopidogrel plus aspirin in ACTIVE-W, the hazard
      ratio (HR) and 95% confidence intervals (95% CIs) for subsequent death associated
      with the occurrence of non-fatal stroke was 5.58 (95% CI 3.84-8.10, P < 0.0001).
      Both ischaemic (HR 5.29, 95% CI 3.53-7.93, P < 0.0001) and haemorrhagic strokes
      (HR 7.38, 95% CI 2.74-19.9, P < 0.0001) increased mortality, but transient
      ischaemic attacks did not. Disabling strokes (Rankin's score > or =3) increased
      mortality (HR 9.54; 95% CI 6.42-14.2, P< 0.0001), but non-disabling strokes did
      not. Severe bleeding increased mortality (HR 3.35, 95% CI 2.12-5.27, P < 0.0001),
      but major bleeding that was not severe according to the study definitions did
      not. CONCLUSION: Non-fatal strokes increased mortality in ACTIVE-W, but non
      disabling strokes did not. Among major bleeding events, only those also
      classified as severe increased mortality. Future research should emphasize the
      prevention of disabling strokes and severe bleeds and place less emphasis on non
      disabling stroke or major bleeds that are not severe.

PMID- 20685677
TI  - A new variety of double-chambered left ventricle.

PMID- 20685678
TI  - Unique haemodynamics in the patient with residual native aortic regurgitation who
      underwent apicoaortic bypass.

PMID- 20685680
TI  - Computed tomography angiography: uncommon findings in an adult patient with
      unrepaired Tetralogy of Fallot.

PMID- 20685679
TI  - Recommendations for the use of cardiac troponin measurement in acute cardiac
      care.
AB  - The release of cardiomyocyte components, i.e. biomarkers, into the bloodstream in
      higher than usual quantities indicates an ongoing pathological process. Thus,
      detection of elevated concentrations of cardiac biomarkers in blood is a sign of
      cardiac injury which could be due to supply-demand imbalance, toxic effects, or
      haemodynamic stress. It is up to the clinician to determine the most probable
      aetiology, the proper therapeutic measures, and the subsequent risk implied by
      the process. For this reason, the measurement of biomarkers always must be
      applied in relation to the clinical context and never in isolation. There are a
      large number of cardiac biomarkers, but they can be subdivided into four broad
      categories, those related to necrosis, inflammation, haemodynamic stress, and/or
      thrombosis. Their usefulness is dependent on the accuracy and reproducibility of
      the measurements, the discriminatory limits separating pathology from physiology,
      and their sensitivity and specificity for specific organ damage and/or disease
      processes. In recent years, cardiac biomarkers have become important adjuncts to
      the delivery of acute cardiac care. Therefore, the Working Group on Acute Cardiac
      Care of the European Society of Cardiology established a committee to deal with
      ongoing and newly developing issues related to cardiac biomarkers. The intention
      of the group is to outline the principles for the application of various
      biomarkers by clinicians in the setting of acute cardiac care in a series of
      expert consensus documents. The first of these will focus on cardiac troponin, a
      pivotal marker of cardiac injury/necrosis.

PMID- 20685681
TI  - Of fads, fashion, surrogate endpoints and dual RAS blockade.
AB  - BACKGROUND: Dual renin-angiotensin system (RAS) blockade, mostly by combining an
      angiotensin converting enzyme (ACE) inhibitor with an angiotensin receptor
      blocker (ARB), is increasingly used in patients with hypertension and diabetes
      and/or proteinuria and in those with resistant heart failure. However, in the
      zest of achieving greater nephroprotection and cardioprotection, even patients
      with uncomplicated essential hypertension are not uncommonly treated with dual
      RAS blockade. EVIDENCE: In 2003 the COOPERATE trial, seemed to confirm that dual
      RAS blockade was beneficial and that proteinuria reduction was synonymous with
      nephroprotection. This study had to be withdrawn recently attesting to the
      suspicion that the data looked to good to be true. Moreover, the large
      prospective ONTARGET data argue against a nephroprotective effect of dual RAS
      blockade and together with renal findings from ACCOMPLISH, cast doubt on
      albuminuria/proteinuria being a reliable surrogate endpoint for renal outcome.
      Although in heart failure, dual RAS blockade had some benefit without reducing
      mortality, there remains a distinct safety issue with regard to hyperkalemia and
      elevated creatinine. Neither in ischaemic heart disease nor in left ventricular
      hypertrophy had dual RAS blockade any benefits when compared with single RAS
      blockade. Of note, the combination of an ACE inhibitor with an ARB was recently
      shown to reduce the risk of dementia. All dual RAS blockade may be created equal
      and the combination of valsartan with aliskiren, a direct renin inhibitor will be
      evaluated in diabetic patients in the prospective, randomized ALTITUDE study.
      CONCLUSIONS: For the time being, given the adverse effects and lack of consistent
      survival benefits, the use of dual RAS blockade should be avoided unless ironclad
      data emerge to the contrary.

PMID- 20685682
TI  - C-reactive protein is a mediator of cardiovascular disease.
AB  - C-reactive protein is postulated to embody an index that can reflect
      cardiovascular risk and can be used to independently predict major cardiovascular
      events and mortality. On the other hand, credible experimental data have become
      available that demonstrate the abundant presence of C-reactive protein in
      atherosclerotic lesions and, moreover, identify C-reactive protein as an
      initiator of several pathogenic pathways that can cause atherogenic changes.
      Consequently, there has been a paradigm shift in which C-reactive protein is no
      longer regarded as merely an indicator of cardiovascular risk, but increasingly
      considered a direct partaker in the pathogenesis of atherosclerotic
      cardiovascular disease. These data underscore the need to explore risk-reducing
      interventions that selectively inhibit C-reactive protein activity as a novel
      strategy to prevent clinical manifestations of atherosclerosis.

PMID- 20685683
TI  - Circulating-water garment or the combination of a circulating-water mattress and
      forced-air cover to maintain core temperature during major upper-abdominal
      surgery.
AB  - BACKGROUND: A recent heat-balance study in volunteers suggested that greater
      efficacy of circulating-water garments (CWGs) results largely from increased heat
      transfer across the posterior skin surface since heat transfer across the
      anterior skin surface was similar with circulating-water and forced-air. We thus
      tested the hypothesis that the combination of a circulating-water mattress (CWM)
      and forced-air warming prevents core temperature reduction during major abdominal
      surgery no worse than a CWG does. METHODS: Fifty adult patients aged between 18
      and 85 yr old, undergoing major abdominal surgery, were randomly assigned to
      intraoperative warming with a combination of forced-air and a CWM or with a CWG
      (Allon ThermoWrap). Core temperature was measured in the distal oesophagus. Non
      inferiority of the CWM to the CWG on change from baseline to median
      intraoperative temperature was assessed using a one-tailed Student's t-test with
      an equivalency buffer of -0.5 degrees C. RESULTS: Data analysis was restricted to
      16 CWG and 20 CWM patients who completed the protocol. Core temperature increased
      in both groups during the initial hours of surgery. We had sufficient evidence
      (P=0.001), to conclude that the combination of a CWM and forced-air warming was
      non-inferior to a CWG in preventing temperature reduction, with mean (95% CI)
      difference in the temperature change between the CWM and the CWG groups (CWM-CWG)
      of 0.46 degrees C (-0.09 degrees C, 1.00 degrees C). CONCLUSIONS: The combination
      of a CWM and forced-air warming is significantly non-inferior in maintaining
      intraoperative core temperature than a CWG. TRIAL REGISTRY: This trial has been
      registered at clinical trials.gov, identifier: NCT 00651898.

PMID- 20685684
TI  - Lateral ultrasound-guided paravertebral blockade: an anatomical-based description
      of a new technique.
AB  - BACKGROUND: Paravertebral blockade (PVB) is a regional anaesthetic technique with
      a large number of indications. PVB is usually performed with landmark-based
      techniques or methods that rely on pressure differences between the extra- and
      intraparavertebral space. This consecutive case series was designed to describe
      the ultrasound appearance of the lateral thoracic paravertebral space (PVS) and
      develop an ultrasound-guided method for PVB. METHODS: The PVS of 20 women
      undergoing breast cancer surgery was investigated with a high-frequency linear
      ultrasound transducer in the sitting position. After identification of the
      transverse process, internal intercostal membrane (IIM), and pleura at the T3 and
      T6 levels, the depths of the IIM and pleura, and the sagittal diameter of the PVS
      were determined. An out-of-plane needle guidance technique was used to perform
      the PVB with ropivacaine 0.75% (12 ml) at both levels. Successful blockade was
      determined by the ability to perform surgery under light general anaesthesia
      without opioids. RESULTS: Appropriate ultrasound identification of the IIM,
      transverse processes, and pleura was possible in all cases. Correct placement of
      the tip of the needle in the PVS resulted in successful PVB. No correlations of
      morphometric data with ultrasound measurements of the PVS were detected.
      CONCLUSIONS: After ultrasound identification of the boundaries of the lateral
      PVS, an out-of-plane needle guidance technique facilitated successful PVB. There
      were no clinically relevant correlations between morphometric data and ultrasound
      measurements.

PMID- 20685686
TI  - Length of delay in seeking medical care by patients with heart failure symptoms
      and the role of symptom-related factors: a narrative review.
AB  - AIMS: The delay in seeking timely medical care by patients with acute coronary
      syndrome and stroke is well established. Less is known about the delay in
      patients with heart failure (HF). Reducing the delay in seeking care and the
      early initiation of treatment is associated with improved outcomes in patients
      with HF. The purpose of this narrative review was to describe the length of the
      delay in seeking care for HF symptoms and identify symptom-related factors that
      contribute to the delay in seeking medical care. METHODS AND RESULTS: A
      literature search was conducted to identify English language studies that (i)
      describe the length of care-seeking delay for HF symptoms and/or (ii) identify
      symptom-related factors that contribute to delay in seeking medical care. The
      results of this review demonstrate that upon hospital admission patients report
      wide variations in median symptom time course from 2 h to 7 days from the onset
      of symptoms to hospital admission. The ability of patients to recognize,
      interpret, and appraise HF symptoms has been demonstrated to be limited. Symptom
      characteristics such as dyspnoea, oedema, orthopnoea, higher somatic awareness,
      higher symptom distress, nocturnal symptom onset, and the pattern of symptom
      onset were related to longer delay in care-seeking for HF symptoms. Furthermore,
      cognitive responses to HF may also play an important role in symptom appraisal.
      CONCLUSION: Delays in seeking care for HF symptoms have been shown to range from
      hours to days from symptom onset to hospital admission. Healthcare professionals
      should therefore be more vigilant in identifying high-risk individuals and
      educating them about the warning signs of HF. Moreover, access to outpatient
      chronic disease management programmes may have the potential to reduce these
      delays.

PMID- 20685685
TI  - Epidemiology and clinical course of heart failure with preserved ejection
      fraction.
AB  - Heart failure with preserved ejection fraction (HFPEF) is increasingly recognized
      as a major public health problem worldwide. Significant advances have been made
      in our understanding of the epidemiology of HFPEF over the past two decades, with
      the publication of numerous population-based epidemiological studies, large heart
      failure registries, and randomized clinical trials. These recent studies have
      provided detailed characterization of larger numbers of patients with HFPEF than
      ever before. This review summarizes the state of current knowledge with regards
      to the disease burden, patient characteristics, clinical course, and outcomes of
      HFPEF. Despite the wealth of available data, substantive gaps in knowledge were
      identified. These gaps represent opportunities for further research in HFPEF, a
      syndrome that is clearly a rising societal burden and that is associated with
      substantial morbidity and mortality.

PMID- 20685687
TI  - Soluble receptor of advanced glycation end products levels are related to
      ischaemic aetiology and extent of coronary disease in chronic heart failure
      patients, independent of advanced glycation end products levels: New Roles for
      Soluble RAGE.
AB  - AIMS: Knowledge of the role of advanced glycation end products (AGE), their
      receptor (RAGE), and the receptor's soluble form (sRAGE), in heart failure (HF)
      is very limited. We evaluated the clinical role of the AGE-RAGE system in HF and
      in particular any association it might have with ischaemic aetiology. METHODS AND
      RESULTS: We measured fluorescent AGE, glycated albumin and sRAGE in 103 patients
      with chronic HF. We showed that sRAGE but not AGE was related to ischaemic
      aetiology (1638.3 +/- 207.4 ischaemic vs. 1065.1 +/- 94.2 pg/mL non-ischaemic
      group; P =0.016) independent of age, sex, diabetes, renal function, clinical
      severity, or other variables (OR: 1.091; 95% CI (confidence interval): 1.032
      1.153; P =0.007). Moreover, sRAGE was directly associated with extent of coronary
      disease (OR for three vessel disease compared with non-coronary lesions: 1.186;
      95% CI: 1.065-1.322; P =0.002). We also found a correlation between sRAGE and
      severity of HF, which increased with New York Heart Association (NYHA) class
      (741.9 +/- 88.9 pg/mL in class 1, 1195.9 +/- 113.2 pg/mL in class II, and 1724.8
      +/- 245.7 pg/mL in class III (P < 0.05)) and brain natriuretic peptide (BNP)
      levels (667.4 +/- 68.0 vs. 1344.5 +/- 126.0 pg/mL for BNP < and >=400 pg/mL,
      respectively). CONCLUSION: sRAGE is an indicator of chronic heart failure
      severity and an independent marker of coronary artery disease and its severity in
      patients with CHF.

PMID- 20685688
TI  - Congestion in chronic systolic heart failure is related to renal dysfunction and
      increased mortality.
AB  - AIMS: To investigate the relationship between signs and symptoms of congestion,
      renal impairment and outcome in chronic heart failure (CHF) patients. METHODS AND
      RESULTS: The Cardiac Insufficiency Bisoprolol Study II included 2647 NYHA class
      III/IV CHF patients. Congestion was estimated by the presence of elevated jugular
      venous pressure, orthopnoea, ascites, or oedema. Glomerular filtration rate
      (eGFR) was estimated using the simplified modification of diet in renal disease
      (sMDRD) formula. The main outcome consisted of all-cause mortality. Mean age was
      61 +/- 11 years, 80% of patients were male, and mean eGFR was 77 +/- 31
      mL/min/1.73 m(2). A total of 1234 (47%) patients had at least one sign, and 10%
      of patients had more than three signs of congestion. Mean eGFR was lower in
      patients with signs of congestion (75 +/- 30 vs. 79 +/- 31 mL/min/1.73 m(2), P <
      0.001). In multivariable analysis, signs of congestion remained independently
      related to eGFR (P = 0.012). Mortality rates almost doubled from no signs to
      three or more signs of congestion (11 vs. 20%, respectively, P < 0.0001).
      Patients with any signs of congestion also had a worse outcome. Adjusted hazard
      ratio was 1.42 (1.14-1.77), P < 0.01 for mortality and 1.21 (1.05-1.39), P < 0.01
      for the composite endpoint. CONCLUSION: Signs and symptoms of congestion are
      associated with renal impairment and are independent determinants of prognosis in
      patients with CHF.

PMID- 20685689
TI  - A large genome scan for rare CNVs in amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease
      selectively affecting motor neurons in the brain and spinal cord. Recent genome
      wide association studies (GWASs) have identified several common variants which
      increase disease susceptibility. In contrast, rare copy-number variants (CNVs),
      which have been associated with several neuropsychiatric traits, have not been
      studied for ALS in well-powered study populations. To examine the role of rare
      CNVs in ALS susceptibility, we conducted a CNV association study including over
      19,000 individuals. In a genome-wide screen of 1875 cases and 8731 controls, we
      did not find evidence for a difference in global CNV burden between cases and
      controls. In our association analyses, we identified two loci that met our
      criteria for follow-up: the DPP6 locus (OR = 3.59, P = 6.6 * 10(-3)), which has
      already been implicated in ALS pathogenesis, and the 15q11.2 locus, containing
      NIPA1 (OR = 12.46, P = 9.3 * 10(-5)), the gene causing hereditary spastic
      paraparesis type 6 (HSP 6). We tested these loci in a replication cohort of 2559
      cases and 5887 controls. Again, results were suggestive of association, but did
      not meet our criteria for independent replication: DPP6 locus: OR = 1.92, P =
      0.097, pooled results: OR = 2.64, P = 1.4 * 10(-3); NIPA1: OR = 3.23, P = 0.041,
      pooled results: OR = 6.20, P = 2.2 * 10(-5)). Our results highlight DPP6 and
      NIPA1 as candidates for more in-depth studies. Unlike other complex neurological
      and psychiatric traits, rare CNVs with high effect size do not play a major role
      in ALS pathogenesis.

PMID- 20685690
TI  - Sarcoidosis HLA class II genotyping distinguishes differences of clinical
      phenotype across ethnic groups.
AB  - The HLA class II (DRB1 and DQB1) associations with sarcoidosis have been studied
      by several groups but often without consistent results. In this paper, we
      consider the hypothesis that observed inconsistencies relate to distinct,
      genetically encoded disease phenotypes which differ in prevalence between
      centres. We therefore typed HLA-DRB1 and DQB1 in 340 UK, 139 Dutch and 163
      Japanese sarcoidosis patients and, respectively, 354, 218 and 168 healthy
      controls from these populations. We applied consistent phenotyping and genotyping
      and investigated associations between HLA class II alleles and distinct disease
      phenotypes within and between ethnic groups. DRB1*01 and DQB1*0501 are protective
      against all manifestations of sarcoidosis. Lung-predominant sarcoidosis is
      associated with DRB1*12 and *14. Lofgren's syndrome is a common sarcoidosis
      phenotype in the Dutch and is strongly associated with the DRB1*0301 allele. This
      phenotype is not seen among the Japanese in whom DRB1*0301 is absent. The same
      allele is protective for UK uveitis. Sarcoid uveitis is common in Japan. The
      DRB1*04-DQB1*0301 haplotype is a risk factor for this disease manifestation in
      Japanese and UK subjects but protective for sarcoidosis overall. We show that
      distinct sarcoidosis phenotypes have similar genetic associations across ethnic
      groups. The disease case mix differs between centres and may be explained by
      different ethnic allelic frequencies.

PMID- 20685691
TI  - Information processing by biochemical networks: a dynamic approach.
AB  - Understanding how information is encoded and transferred by biochemical networks
      is of fundamental importance in cellular and systems biology. This requires
      analysis of the relationships between the stochastic trajectories of the
      constituent molecular (or submolecular) species that comprise the network. We
      describe how to identify conditional independences between the trajectories or
      time courses of groups of species. These are robust network properties that
      provide important insight into how information is processed. An entire network
      can then be decomposed exactly into modules on informational grounds. In the
      context of signalling networks with multiple inputs, the approach identifies the
      routes and species involved in sequential information processing between input
      and output modules. An algorithm is developed which allows automated
      identification of decompositions for large networks and visualization using a
      tree that encodes the conditional independences. Only stoichiometric information
      is used and neither simulations nor knowledge of rate parameters are required. A
      bespoke version of the algorithm for signalling networks identifies the routes of
      sequential encoding between inputs and outputs, visualized as paths in the tree.
      Application to the toll-like receptor signalling network reveals that inputs can
      be informative in ways unanticipated by steady-state analyses, that the
      information processing structure is not well described as a bow tie, and that
      encoding for the interferon response is unusually sparse compared with other
      outputs of this innate immune system.

PMID- 20685692
TI  - A moment invariant for evaluating the chirality of three-dimensional objects.
AB  - Chirality is an important feature of three-dimensional objects and a key concept
      in chemistry, biology and many other disciplines. However, it has been difficult
      to quantify, largely owing to computational complications. Here we present a
      general chirality measure, called the chiral invariant (CI), which is applicable
      to any three-dimensional object containing a large amount of data. The CI
      distinguishes the hand of the object and quantifies the degree of its handedness.
      It is invariant to the translation, rotation and scale of the object, and
      tolerant to a modest amount of noise in the experimental data. The invariant is
      expressed in terms of moments and can be computed in almost no time. Because of
      its universality and computational efficiency, the CI is suitable for a wide
      range of pattern-recognition problems. We demonstrate its applicability to
      molecular atomic models and their electron density maps. We show that the
      occurrence of the conformations of the macromolecular polypeptide backbone is
      related to the value of the CI of the constituting peptide fragments. We also
      illustrate how the CI can be used to assess the quality of a crystallographic
      electron density map.

PMID- 20685693
TI  - In situ ATR-IR spectroscopic and electron microscopic analyses of settlement
      secretions of Undaria pinnatifida kelp spores.
AB  - Knowledge about the settlement of marine organisms on substrates is important for
      the development of environmentally benign new methods for control of marine
      biofouling. The adhesion to substrates by spores of Undaria pinnatifida, a kelp
      species that is invasive to several countries, was studied by scanning electron
      and transmission electron microscopies (SEM/TEM) as well as by in situ attenuated
      total reflection infrared (ATR-IR) spectroscopy. The IR spectra showed that
      adhesive secretion began approximately 15 min after initial settlement and that
      the adhesive bulk material contained protein and anionic polysaccharides. Energy
      dispersive X-ray microanalysis of the adhesive identified sulphur and phosphorus
      as well as calcium and magnesium ions, which facilitate the gelation of the
      anionic polysaccharides in the sea water. The adhesive may be secreted from Golgi
      bodies in the spore, which were imaged by TEM of spore thin sections.
      Additionally, an in situ settlement study on TiO(2) particle film by ATR-IR
      spectroscopy revealed the presence of phosphorylated moieties directly binding
      the substrate. The presence of anionic groups dominating the adhesive suggests
      that inhibition of spore adhesion will be favoured by negatively charged
      surfaces.

PMID- 20685694
TI  - Group dynamics and record signals in the ant Temnothorax albipennis.
AB  - Many purely physical complex systems, in which there are both stochasticity and
      local interactions between the components, exhibit record dynamics. The temporal
      statistics of record dynamics is a Poisson process operating on a logarithmic
      rather than a linear time scale (i.e. a log-Poisson process). Record dynamics
      often drive substantial changes in complex systems when new high water marks in
      partially stochastic processes trigger new events. Social insect colonies are
      exemplary complex biological systems in which many of the local interactions of
      the components have been moulded by natural selection for the common good. Here,
      we combine experimental manipulation of ant colony demography with modelling to
      test the hypothesis that social interactions are the mechanism underlying the
      record dynamics. We found that compared with the control, log-Poisson statistics
      were disrupted in colonies in which the pattern of interactions was modified by
      the removal of the brood, and disappeared completely in 'callow' colonies
      composed entirely of very young workers from the same age cohort. We conclude
      that a subtle interplay between the demography of the society and the pattern of
      the interactions between the ants is crucial for the emergence of record
      dynamics. This could help identify what makes an ant colony a cohesive society.

PMID- 20685695
TI  - Social olfaction in marine mammals: wild female Australian sea lions can identify
      their pup's scent.
AB  - Historically, anatomical evidence has suggested that marine mammals are anosmic
      or at best microsmatic, i.e. absent or reduced olfactory capabilities. However,
      these neuroanatomical considerations may not be appropriate predictors for the
      use of olfaction in social interactions. Observations suggest that pinnipeds may
      use olfaction in mother-pup interactions, accepting or rejecting pups after naso
      nasal contact. Such maternal-offspring recognition is a favourable area for
      investigating the involvement of odours in social recognition and selectivity, as
      females are evolutionarily constrained to direct resources to filial young.
      However, there is no experimental, morphological or chemical evidence to date for
      the use of olfaction in social contexts and for individual odour recognition
      abilities in pinnipeds. Here, we report unequivocal evidence that Australian sea
      lion (Neophoca cinerea) females can differentiate between the odour of their own
      pup and that of another, in the absence of any other distinguishing cues. This
      study demonstrates individual olfactory recognition in a free-ranging wild mammal
      and is clear evidence of the social function of olfaction in a marine mammal.

PMID- 20685696
TI  - Male response to historical and geographical variation in bird song.
AB  - In many species, individuals discriminate among sexual signals of conspecific
      populations in the contexts of mate choice and male-male competition. Differences
      in signals among populations (geographical variation) are in part the result of
      signal evolution within populations (temporal variation). Understanding the
      relative effect of temporal and geographical signal variation on signal salience
      may therefore provide insight into the evolution of behavioural discrimination.
      However, no study, to my knowledge, has compared behavioural response to
      historical signals with response to current signal variation among populations.
      Here, I measured the response of male white-crowned sparrows (Zonotrichia
      leucophrys) to historical songs compared with current songs from their local
      population, a nearby non-local population and a distant population. Males
      responded most strongly to current local songs, less, but equally, to historical
      local and current non-local songs, and least to songs of the distant population.
      Moreover, response to both temporal and geographical variation in song was
      proportional to how much songs differed acoustically from current local songs.
      Signal evolution on an ecological time scale appears to have an effect on signal
      salience comparable to differences found between current neighbouring
      populations, supporting the idea that behavioural discrimination among learned
      signals of conspecific populations can evolve relatively rapidly.

PMID- 20685697
TI  - Reproductive competition and the evolution of extreme birth synchrony in a
      cooperative mammal.
AB  - Reproductive events in animal societies often show a high degree of temporal
      clustering, but the evolutionary causes of this synchronization are poorly
      understood. Here, we suggest that selection to avoid the negative effects of
      competition with other females has given rise to a remarkable degree of birth
      synchrony in the communal-breeding banded mongoose (Mungos mungo). Within banded
      mongoose groups, births are highly synchronous, with 64 per cent of females
      giving birth on exactly the same night. Our results indicate that this extreme
      synchrony arises because offspring suffer an increased risk of infanticide if
      their mother gives birth before other females, but suffer in competition with
      older littermates if their mother gives birth after them. These findings
      highlight the important influence that reproductive competition can have for the
      evolution of reproductive synchrony.

PMID- 20685698
TI  - A soft-bodied lophophorate from the Silurian of England.
AB  - Soft-bodied taxa comprise an important component of the extant lophophorate
      fauna, but convincing fossils of soft-bodied lophophorates are extremely rare. A
      small fossil lophophorate, attached to a brachiopod dorsal valve, is described
      from the Silurian (Wenlock Series) Herefordshire Lagerstatte of England. This
      unmineralized organism was bilaterally symmetrical and comprised a subconical
      body attached basally to the host and partially enclosed by a broad 'hood'; the
      body bore a small, coiled lophophore. Where the hood attached laterally, there is
      a series of transverse ridges and furrows. The affinities of this organism
      probably lie with Brachiopoda; the hood is interpreted as the homologue of a
      dorsal valve/mantle lobe, and the attachment as the homologue of the ventral
      valve and/or pedicle. The ridges are arranged in a manner that suggests
      constructional serial repetition, indicating that they are unlikely to represent
      mantle canals. Extant brachiopods are not serially structured, but morphological
      and molecular evidence suggests that their ancestors were. The new organism may
      belong to the brachiopod stem group, and might also represent a significant
      element of the Palaeozoic lophophorate fauna.

PMID- 20685699
TI  - Plant species richness, identity and productivity differentially influence key
      groups of microbes in grassland soils of contrasting fertility.
AB  - The abundance of microbes in soil is thought to be strongly influenced by plant
      productivity rather than by plant species richness per se. However, whether this
      holds true for different microbial groups and under different soil conditions is
      unresolved. We tested how plant species richness, identity and biomass influence
      the abundances of arbuscular mycorrhizal fungi (AMF), saprophytic bacteria and
      fungi, and actinomycetes, in model plant communities in soil of low and high
      fertility using phospholipid fatty acid analysis. Abundances of saprophytic fungi
      and bacteria were driven by larger plant biomass in high diversity treatments. In
      contrast, increased AMF abundance with larger plant species richness was not
      explained by plant biomass, but responded to plant species identity and was
      stimulated by Anthoxantum odoratum. Our results indicate that the abundance of
      saprophytic soil microbes is influenced more by resource quantity, as driven by
      plant production, while AMF respond more strongly to resource composition, driven
      by variation in plant species richness and identity. This suggests that AMF
      abundance in soil is more sensitive to changes in plant species diversity per se
      and plant species composition than are abundances of saprophytic microbes.

PMID- 20685700
TI  - Population admixture, biological invasions and the balance between local
      adaptation and inbreeding depression.
AB  - When previously isolated populations meet and mix, the resulting admixed
      population can benefit from several genetic advantages, including increased
      genetic variation, the creation of novel genotypes and the masking of deleterious
      mutations. These admixture benefits are thought to play an important role in
      biological invasions. In contrast, populations in their native range often remain
      differentiated and frequently suffer from inbreeding depression owing to
      isolation. While the advantages of admixture are evident for introduced
      populations that experienced recent bottlenecks or that face novel selection
      pressures, it is less obvious why native range populations do not similarly
      benefit from admixture. Here we argue that a temporary loss of local adaptation
      in recent invaders fundamentally alters the fitness consequences of admixture. In
      native populations, selection against dilution of the locally adapted gene pool
      inhibits unconstrained admixture and reinforces population isolation, with some
      level of inbreeding depression as an expected consequence. We show that admixture
      is selected against despite significant inbreeding depression because the
      benefits of local adaptation are greater than the cost of inbreeding. In
      contrast, introduced populations that have not yet established a pattern of local
      adaptation can freely reap the benefits of admixture. There can be strong
      selection for admixture because it instantly lifts the inbreeding depression that
      had built up in isolated parental populations. Recent work in Silene suggests
      that reduced inbreeding depression associated with post-introduction admixture
      may contribute to enhanced fitness of invasive populations. We hypothesize that
      in locally adapted populations, the benefits of local adaptation are balanced
      against an inbreeding cost that could develop in part owing to the isolating
      effect of local adaptation itself. The inbreeding cost can be revealed in
      admixing populations during recent invasions.

PMID- 20685701
TI  - Antagonistic coevolution with parasites maintains host genetic diversity: an
      experimental test.
AB  - Genetic variation in natural populations is a prime prerequisite allowing
      populations to respond to selection, but is under constant threat from forces
      that tend to reduce it, such as genetic drift and many types of selection.
      Haldane emphasized the potential importance of parasites as a driving force of
      genetic diversity. His theory has been taken for granted ever since, but despite
      numerous studies showing correlations between genetic diversity and parasitism,
      Haldane's hypothesis has rarely been tested experimentally for unambiguous
      support. We experimentally staged antagonistic coevolution between the host
      Tribolium castaneum and its natural microsporidian parasite, Nosema whitei, to
      test for the relative importance of two separate evolutionary forces (drift and
      parasite-induced selection) on the maintenance of genetic variation. Our results
      demonstrate that coevolution with parasites indeed counteracts drift as
      coevolving populations had significantly higher levels of heterozygosity and
      allelic diversity. Genetic drift remained a strong force, strongly reducing
      genetic variation and increasing genetic differentiation in small populations. To
      our surprise, differentiation between the evolving populations was smaller when
      they coevolved with parasites, suggesting parallel balancing selection. Hence,
      our results experimentally vindicate Haldane's original hypothesis 60 years after
      its conception.

PMID- 20685702
TI  - Competition limits adaptation and productivity in a photosynthetic alga at
      elevated CO2.
AB  - When competitive exclusion between lineages and genetic adaptation within
      lineages occur on the same timescale, the two processes have the potential to
      interact. I use experimental microbial evolution where strains of a
      photosynthetic microbe that differ in their physiological response to CO(2)
      enrichment are grown either alone or in communities for hundreds of generations
      under CO(2) enrichment. After about 300 generations of growth, strains that
      experienced competition while adapting to environmental change are both less
      productive and less fit than corresponding strains that adapted to that same
      environmental change in the absence of competitors. In addition, I find that
      excluding competitors not only limits that strain's adaptive response to abiotic
      change, but also decreases community productivity; I quantify this effect using
      the Price equation. Finally, these data allow me to empirically test the common
      hypothesis that phytoplankton that are most able to take advantage of carbon
      enrichment in single-strain populations over the short term will increase in
      frequency within multi-strain communities over longer timescales.

PMID- 20685703
TI  - Individual variation in behavioural plasticity: direct and indirect effects of
      boldness, exploration and sociability on habituation to predators in lizards.
AB  - Little is known about the factors causing variation in behavioural plasticity and
      the interplay between personality and plasticity. Habituation to predators is a
      special case of behavioural plasticity. We investigated the direct and indirect
      effects of boldness, exploration and sociability traits on the habituation
      ability of Iberian wall lizards, considering exposure and sex effects. Individual
      boldness was consistent across several non-habituation contexts, but it did not
      significantly affect habituation. Exploration had a strong direct effect on
      habituation, with more exploratory individuals being able to habituate faster
      than less exploratory ones, probably because of their ability to assess risk
      better. Individual variation in habituation was also affected by sociability, but
      this was an indirect effect mediated by exposure to the predator. Less social
      individuals avoided refuges with conspecific cues, increasing exposure to the
      predator and eventually habituation. Finally, the direct effects of sex (females
      habituated faster than males) were opposite to its indirect effects through
      exposure. We conclude that risk assessment, instead of the proactivity-reactivity
      gradient usually considered in the literature, can affect behavioural plasticity
      through complex interactions between direct and indirect effects, including
      exploratory behaviour, degree of exposure to the predator and sex, which
      represent novel mechanisms generating inter-individual variation in plasticity.

PMID- 20685704
TI  - Interactions among thermal parameters determine offspring sex under temperature
      dependent sex determination.
AB  - In many animals, temperatures experienced by developing embryos determine
      offspring sex (e.g. temperature-dependent sex determination, TSD), but most
      studies focus strictly on the effects of mean temperature, with little emphasis
      on the importance of thermal fluctuations. In the jacky dragon (Amphibolurus
      muricatus), an Australian lizard with TSD, data from nests in the field
      demonstrate that offspring sex ratios are predictable from thermal fluctuations
      but not from mean nest temperatures. To clarify this paradox, we incubated eggs
      in a factorial experiment with two levels of mean temperature and three levels of
      diel fluctuation. We show that offspring sex is determined by an interaction
      between these critical thermal parameters. Intriguingly, because these two
      thermal descriptors shift in opposing directions throughout the incubation
      season, this interactive effect inhibits seasonal shifts in sex ratio. Hence, our
      results suggest that TSD can yield offspring sex ratios that resemble those
      produced under genotypic sex-determining systems. These findings raise important
      considerations for understanding the diversity of TSD reaction norms, for
      designing experiments that evaluate the evolutionary significance of TSD, and for
      predicting sex ratios under past and future climate change scenarios.

PMID- 20685705
TI  - Rapid parallel adaptive radiations from a single hybridogenic ancestral
      population.
AB  - The Alpine lake whitefish (Coregonus lavaretus) species complex is a classic
      example of a recent radiation, associated with colonization of the Alpine lakes
      following the glacial retreat (less than 15 kyr BP). They have formed a unique
      array of endemic lake flocks, each with one to six described sympatric species
      differing in morphology, diet and reproductive ecology. Here, we present a
      genomic investigation of the relationships between and within the lake flocks.
      Comparing the signal between over 1000 AFLP loci and mitochondrial control region
      sequence data, we use phylogenetic tree-based and population genetic methods to
      reconstruct the phylogenetic history of the group and to delineate the principal
      centres of genetic diversity within the radiation. We find significant
      cytonuclear discordance showing that the genomically monophyletic Alpine
      whitefish clade arose from a hybrid swarm of at least two glacial refugial
      lineages. Within this radiation, we find seven extant genetic clusters centred on
      seven lake systems. Most interestingly, we find evidence of sympatric speciation
      within and parallel evolution of equivalent phenotypes among these lake systems.
      However, we also find the genetic signature of human-mediated gene flow and
      diversity loss within many lakes, highlighting the fragility of recent
      radiations.

PMID- 20685706
TI  - An integrative and functional framework for the study of animal emotion and mood.
AB  - A better understanding of animal emotion is an important goal in disciplines
      ranging from neuroscience to animal welfare science. The conscious experience of
      emotion cannot be assessed directly, but neural, behavioural and physiological
      indicators of emotion can be measured. Researchers have used these measures to
      characterize how animals respond to situations assumed to induce discrete
      emotional states (e.g. fear). While advancing our understanding of specific
      emotions, this discrete emotion approach lacks an overarching framework that can
      incorporate and integrate the wide range of possible emotional states.
      Dimensional approaches that conceptualize emotions in terms of universal core
      affective characteristics (e.g. valence (positivity versus negativity) and
      arousal) can provide such a framework. Here, we bring together discrete and
      dimensional approaches to: (i) offer a structure for integrating different
      discrete emotions that provides a functional perspective on the adaptive value of
      emotional states, (ii) suggest how long-term mood states arise from short-term
      discrete emotions, how they also influence these discrete emotions through a bi
      directional relationship and how they may function to guide decision-making, and
      (iii) generate novel hypothesis-driven measures of animal emotion and mood.

PMID- 20685707
TI  - Odour signals major histocompatibility complex genotype in an Old World monkey.
AB  - The major histocompatibility complex (MHC) is an extraordinarily diverse cluster
      of genes that play a key role in the immune system. MHC gene products are also
      found in various body secretions, leading to the suggestion that MHC genotypes
      are linked to unique individual odourtypes that animals use to assess the
      suitability of other individuals as potential mates or social partners. We
      investigated the relationship between chemical odour profiles and genotype in a
      large, naturally reproducing population of mandrills, using gas chromatography
      mass spectrometry and MHC genotyping. Odour profiles were not linked to the
      possession of particular MHC supertypes. Sex influenced some measures of odour
      diversity and dominance rank influenced some measures of odour diversity in
      males, but not in females. Odour similarity was strongly related to similarity at
      the MHC, and, in some cases, to pedigree relatedness. Our results suggest that
      odour provides both a cue of individual genetic quality and information against
      which the receiver can compare its own genotype to assess genetic similarity.
      These findings provide a potential mechanism underlying mate choice for genetic
      diversity and MHC similarity as well as kin selection.

PMID- 20685708
TI  - Limits to the evolution of assortative mating by female choice under restricted
      gene flow.
AB  - The evolution of assortative mating is a key component of the process of
      speciation with gene flow. Several recent theoretical studies have pointed out,
      however, that sexual selection which can result from assortative mating may cause
      it to plateau at an intermediate level; this is primarily owing to search costs
      of individuals with extreme phenotypes and to assortative preferences developed
      by individuals with intermediate phenotypes. I explore the limitations of
      assortative mating further by analysing a simple model in which these factors
      have been removed. Specifically, I use a haploid two-population model to ask
      whether the existence of assortative mating is sufficient to drive the further
      evolution of assortative mating. I find that a weakening in the effective
      strength of sexual selection with strong assortment leads to the existence of
      both a peak level of trait differentiation and the evolution of an intermediate
      level of assortative mating that will cause that peak. This result is robust to
      the inclusion of local adaptation and different genetic architecture of the
      trait. The results imply the existence of fundamental limits to the evolution of
      assortment via sexual selection in this situation, with which other factors, such
      as search costs, may interact.

PMID- 20685709
TI  - Affective consciousness in animals: perspectives on dimensional and primary
      process emotion approaches.

PMID- 20685710
TI  - Phenotypic evolution of dispersal-enhancing traits in insular voles.
AB  - Evolutionary theory predicts that in metapopulations subject to rapid extinction
      recolonization dynamics, natural selection should favour evolution of traits that
      enhance dispersal and recolonization ability. Metapopulations of field voles
      (Microtus agrestis) on islands in the Stockholm archipelago, Sweden, are
      characterized by frequent local extinction and recolonization of subpopulations.
      Here, we show that voles on the islands were larger and had longer feet than
      expected for their body size, compared with voles from the mainland; that body
      size and size-specific foot length increased with increasing geographical
      isolation and distance from mainland; and that the differences in body size and
      size-specific foot length were genetically based. These findings provide rare
      evidence for relatively recent (less than 1000 years) and rapid (corresponding to
      100-250 darwins) evolution of traits facilitating dispersal and recolonization in
      island metapopulations.

PMID- 20685711
TI  - An enzootic vector-borne virus is amplified at epizootic levels by an invasive
      avian host.
AB  - Determining the effect of an invasive species on enzootic pathogen dynamics is
      critical for understanding both human epidemics and wildlife epizootics.
      Theoretical models suggest that when a naive species enters an established host
      parasite system, the new host may either reduce ('dilute') or increase
      ('spillback') pathogen transmission to native hosts. There are few empirical data
      to evaluate these possibilities, especially for animal pathogens. Buggy Creek
      virus (BCRV) is an arthropod-borne alphavirus that is enzootically transmitted by
      the swallow bug (Oeciacus vicarius) to colonially nesting cliff swallows
      (Petrochelidon pyrrhonota). In western Nebraska, introduced house sparrows
      (Passer domesticus) invaded cliff swallow colonies approximately 40 years ago and
      were exposed to BCRV. We evaluated how the addition of house sparrows to this
      host-parasite system affected the prevalence and amplification of a bird
      associated BCRV lineage. The infection prevalence in house sparrows was eight
      times that of cliff swallows. Nestling house sparrows in mixed-species colonies
      were significantly less likely to be infected than sparrows in single-species
      colonies. Infected house sparrows circulated BCRV at higher viraemia titres than
      cliff swallows. BCRV detected in bug vectors at a site was positively associated
      with virus prevalence in house sparrows but not with virus prevalence in cliff
      swallows. The addition of a highly susceptible invasive host species has led to
      perennial BCRV epizootics at cliff swallow colony sites. The native cliff swallow
      host confers a dilution advantage to invasive sparrow hosts in mixed colonies,
      while at the same sites house sparrows may increase the likelihood that swallows
      become infected.

PMID- 20685712
TI  - Estimating the age of fire in the Cape flora of South Africa from an orchid
      phylogeny.
AB  - Fire may have been a crucial component in the evolution of the Cape flora of
      South Africa, a region characterized by outstanding levels of species richness
      and endemism. However, there is, to date, no critical assessment of the age of
      the modern fire regime in this biome. Here, we exploit the presence of two
      obligate post-fire flowering clades in the orchid genus Disa, in conjunction with
      a robust, well-sampled and dated molecular phylogeny, to estimate the age by
      which fire must have been present. Our results indicate that summer drought
      (winter rainfall), the fire regime and the fynbos vegetation are several million
      years older than currently suggested. Summer drought and the fynbos vegetation
      are estimated to date back to at least the Early Miocene (ca 19.5 Ma). The
      current fire regime may have been established during a period of global cooling
      that followed the mid-Miocene Climatic Optimum (ca 15 Ma), which led to the
      expansion of open habitats and increased aridification. The first appearance of
      Disa species in the grassland biome, as well as in the subalpine habitat, is in
      striking agreement with reliable geological and palaeontological evidence of the
      age of these ecosystems, thus corroborating the efficacy of our methods. These
      results change our understanding of the historical mechanisms underlying
      botanical evolution in southern Africa, and confirm the potential of using
      molecular phylogenies to date events for which other information is lacking or
      inconclusive.

PMID- 20685713
TI  - Degraded lands worth protecting: the biological importance of Southeast Asia's
      repeatedly logged forests.
AB  - Southeast Asia is a hotspot of imperiled biodiversity, owing to extensive logging
      and forest conversion to oil palm agriculture. The degraded forests that remain
      after multiple rounds of intensive logging are often assumed to be of little
      conservation value; consequently, there has been no concerted effort to prevent
      them from being converted to oil palm. However, no study has quantified the
      biodiversity of repeatedly logged forests. We compare the species richness and
      composition of birds and dung beetles within unlogged (primary), once-logged and
      twice-logged forests in Sabah, Borneo. Logging had little effect on the overall
      richness of birds. Dung beetle richness declined following once-logging but did
      not decline further after twice-logging. The species composition of bird and dung
      beetle communities was altered, particularly after the second logging rotation,
      but globally imperiled bird species (IUCN Red List) did not decline further after
      twice-logging. Remarkably, over 75 per cent of bird and dung beetle species found
      in unlogged forest persisted within twice-logged forest. Although twice-logged
      forests have less biological value than primary and once-logged forests, they
      clearly provide important habitat for numerous bird and dung beetle species.
      Preventing these degraded forests from being converted to oil palm should be a
      priority of policy-makers and conservationists.

PMID- 20685714
TI  - Warming reduces metabolic rate in marine snails: adaptation to fluctuating high
      temperatures challenges the metabolic theory of ecology.
AB  - The universal temperature-dependence model (UTD) of the metabolic theory of
      ecology (MTE) proposes that temperature controls mass-scaled, whole-animal
      resting metabolic rate according to the first principles of physics (Boltzmann
      kinetics). Controversy surrounds the model's implication of a mechanistic basis
      for metabolism that excludes the effects of adaptive regulation, and it is
      unclear how this would apply to organisms that live in fringe environments and
      typically show considerable metabolic adaptation. We explored thermal scaling of
      metabolism in a rocky-shore eulittoral-fringe snail (Echinolittorina malaccana)
      that experiences constrained energy gain and fluctuating high temperatures
      (between 25 degrees C and approximately 50 degrees C) during prolonged emersion
      (weeks). In contrast to the prediction of the UTD model, metabolic rate was often
      negatively related to temperature over a benign range (30-40 degrees C), the
      relationship depending on (i) the temperature range, (ii) the degree of metabolic
      depression (related to the quiescent period), and (iii) whether snails were
      isolated within their shells. Apparent activation energies (E) varied between
      0.05 and -0.43 eV, deviating excessively from the UTD's predicted range of
      between 0.6 and 0.7 eV. The lowering of metabolism when heated should improve
      energy conservation in a high-temperature environment and challenges both the
      theory's generality and its mechanistic basis.

PMID- 20685715
TI  - Rapid evolution of cold tolerance in stickleback.
AB  - Climate change is predicted to lead to increased average temperatures and greater
      intensity and frequency of high and low temperature extremes, but the
      evolutionary consequences for biological communities are not well understood.
      Studies of adaptive evolution of temperature tolerance have typically involved
      correlative analyses of natural populations or artificial selection experiments
      in the laboratory. Field experiments are required to provide estimates of the
      timing and strength of natural selection, enhance understanding of the genetics
      of adaptation and yield insights into the mechanisms driving evolutionary change.
      Here, we report the experimental evolution of cold tolerance in natural
      populations of threespine stickleback fish (Gasterosteus aculeatus). We show that
      freshwater sticklebacks are able to tolerate lower minimum temperatures than
      marine sticklebacks and that this difference is heritable. We transplanted marine
      sticklebacks to freshwater ponds and measured the rate of evolution after three
      generations in this environment. Cold tolerance evolved at a rate of 0.63
      haldanes to a value 2.5 degrees C lower than that of the ancestral population,
      matching values found in wild freshwater populations. Our results suggest that
      cold tolerance is under strong selection and that marine sticklebacks carry
      sufficient genetic variation to adapt to changes in temperature over remarkably
      short time scales.

PMID- 20685716
TI  - Effects of cigarette smoking on reproduction.
AB  - BACKGROUND Cigarette smoking is associated with lower fecundity rates, adverse
      reproductive outcomes and a higher risk of IVF failures. Over the last few
      decades, prevalence of smoking among women of reproductive age has increased.
      This review focuses on current knowledge of the potential effects of smoke
      toxicants on all reproductive stages and the consequences of smoke exposure on
      reproductive functions. METHODS We conducted a systematic review of the
      scientific literature on the impact of cigarette smoking and smoke constituents
      on the different stages of reproductive function, including epidemiological,
      clinical and experimental studies. We attempted to create hypotheses and find
      explanations for the deleterious effects of cigarette smoke observed in
      experimental studies. RESULTS Cigarette smoke contains several thousand
      components (e.g. nicotine, polycyclic aromatic hydrocarbons and cadmium) with
      diverse effects. Each stage of reproductive function, folliculogenesis,
      steroidogenesis, embryo transport, endometrial receptivity, endometrial
      angiogenesis, uterine blood flow and uterine myometrium is a target for cigarette
      smoke components. The effects of cigarette smoke are dose-dependent and are
      influenced by the presence of other toxic substances and hormonal status.
      Individual sensitivity, dose, time and type of exposure also play a role in the
      impact of smoke constituents on human fertility. CONCLUSIONS All stages of
      reproductive functions are targets of cigarette smoke toxicants. Further studies
      are necessary to better understand the deleterious effects of cigarette smoke
      compounds on the reproductive system in order to improve health care, help to
      reduce cigarette smoking and provide a better knowledge of the molecular
      mechanisms involved in reproductive toxicology.

PMID- 20685717
TI  - Ultrafine particles emitted by flame and electric arc guns for thermal spraying
      of metals.
AB  - The ultrafine aerosol emitted by thermal spraying of metals using flame and
      electric arc processes has been characterized in terms of particle size
      distribution and emission rates based on both particle number and mass. Thermal
      spraying of Zn, Zn/Al, and Al was studied. Measurements taken using an electrical
      low pressure impactor and a condensation nucleus counter reveal an aerosol made
      up of very fine particles (80-95% of number distribution <100 nm). Ultrafine
      particle emission rates produced by the electric arc process are very high, the
      largest values being recorded during spraying of pure aluminium. This process
      generates high particle emissions and therefore requires careful consideration
      and possible rethinking of currently implemented protection measures: ventilated
      cabins, dust collectors, and personal protective equipment.

PMID- 20685718
TI  - Phase II study of helical tomotherapy for oligometastatic colorectal cancer.
AB  - BACKGROUND: To evaluate the efficacy and toxicity of helical tomotherapy in the
      treatment of oligometastatic colorectal cancer (CRC) patients who were not
      amenable for metastasectomy and/or (further) systemic treatment. PATIENTS AND
      METHODS: CRC patients with five or less metastases were enrolled. No limitations
      concerning dimension or localization of the metastases were imposed. Patients
      were treated with intensity-modulated and image-guided radiotherapy using helical
      tomotherapy, delivering a total dose of 40 Gy in fractions of 4 Gy. Positron
      emission tomography-computed tomography (PET-CT) was carried out at baseline and
      3 months after the initiation of radiotherapy to evaluate the metabolic response
      rate according to PET Response Criteria in Solid Tumors (PERCIST) version 1.0.
      Side-effects were scored using National Cancer Institute Common Terminology
      Criteria for Adverse Events (NCI-CTC AE) version 3.0. RESULTS: Twenty-three
      patients were enrolled. A total of 52 metastases were treated. One patient (4%)
      experienced grade 3 vomiting; two patients (9%) grade 2 diarrhea and dysphagia,
      respectively. Twenty-two patients were evaluated by post-treatment PET-CT. Five
      (23%) and seven patients (32%) achieved a complete and partial metabolic
      response, respectively, resulting in an overall metabolic response rate of 55%.
      The actuarial 1-year local control, progression-free survival, and overall
      survival were 54%, 25% and 86%, respectively. CONCLUSION: The use of helical
      tomotherapy in oligometastatic CRC patients resulted in a promising metabolic
      response rate of 55%.

PMID- 20685719
TI  - Molecular evolution of cytochrome C oxidase underlies high-altitude adaptation in
      the bar-headed goose.
AB  - Bar-headed geese (Anser indicus) fly at up to 9,000 m elevation during their
      migration over the Himalayas, sustaining high metabolic rates in the severe
      hypoxia at these altitudes. We investigated the evolution of cardiac energy
      metabolism and O(2) transport in this species to better understand the molecular
      and physiological mechanisms of high-altitude adaptation. Compared with low
      altitude geese (pink-footed geese and barnacle geese), bar-headed geese had
      larger lungs and higher capillary densities in the left ventricle of the heart,
      both of which should improve O(2) diffusion during hypoxia. Although myoglobin
      abundance and the activities of many metabolic enzymes (carnitine
      palmitoyltransferase, citrate synthase, 3-hydroxyacyl-coA dehydrogenase, lactate
      dehydrogenase, and pyruvate kinase) showed only minor variation between species,
      bar-headed geese had a striking alteration in the kinetics of cytochrome c
      oxidase (COX), the heteromeric enzyme that catalyzes O(2) reduction in oxidative
      phosphorylation. This was reflected by a lower maximum catalytic activity and a
      higher affinity for reduced cytochrome c. There were small differences between
      species in messenger RNA and protein expression of COX subunits 3 and 4, but
      these were inconsistent with the divergence in enzyme kinetics. However, the COX3
      gene of bar-headed geese contained a nonsynonymous substitution at a site that is
      otherwise conserved across vertebrates and resulted in a major functional change
      of amino acid class (Trp-116 -> Arg). This mutation was predicted by structural
      modeling to alter the interaction between COX3 and COX1. Adaptations in
      mitochondrial enzyme kinetics and O(2) transport capacity may therefore
      contribute to the exceptional ability of bar-headed geese to fly high.

PMID- 20685720
TI  - Differential expression profiling analyses identifies downregulation of 1p, 6q,
      and 14q genes and overexpression of 6p histone cluster 1 genes as markers of
      recurrence in meningiomas.
AB  - The majority of meningiomas are probably benign but a number of tumors display
      considerable histological and/or clinical aggressivity, sometimes with
      unexpectedly high recurrence rates after radical removal. Understanding the
      potential behavior of these tumors in individual patients is critical for
      rational therapeutic decision-making. This study aimed to identify gene
      expression profiles and candidate markers associated with original and recurrent
      meningiomas. Unsupervised hierarchical clustering of the samples confirmed 2 main
      groups of meningiomas with distinct clinical behaviors. The gene expression
      profiling study identified genes and pathways potentially associated with
      meningioma recurrence, revealing an overall lower level of gene expression. The
      differential gene expression profiling analyses of original and recurrent
      meningiomas identified 425 known genes and expressed sequence tags related to
      meningioma recurrence, with SFRP1 (8p12), TMEM30B (14q23), and CTGF (6q23)
      showing the most disparate expression. Most of the differentially expressed genes
      were located at 1p, 6q, and 14q and were underexpressed in recurrences. Loss of
      such chromosomal regions has previously been associated with a higher risk of
      meningioma recurrence or malignant progression. Thus, at these locations, we
      propose the existence of novel candidate genes that could be involved in
      meningioma recurrence. In addition, the overexpression of genes of histone
      cluster 1 (6p) in recurrent meningiomas is reported here for the first time.
      Finally, the altered genes related to meningioma recurrence are involved in
      pathways such as Notch, TGFbeta, and Wnt, as described previously, and in other
      pathways such as cell cycle, oxidative phosphorylation, PPAR, and PDGF, not
      related before to meningioma recurrence.

PMID- 20685721
TI  - Pulsed radiofrequency versus conventional transcutaneous electrical nerve
      stimulation in painful shoulder: a prospective, randomized study.
AB  - OBJECTIVE: To compare the efficacy of pulse radiofrequency applied to the
      suprascapular nerve with the efficacy of conventional transcutaneous electrical
      nerve stimulation treatment in patients with shoulder pain. DESIGN: A randomized,
      controlled trial. SETTING: An outpatient physical therapy and rehabilitation
      clinic. SUBJECTS: Forty patients with shoulder pain lasting at least three months
      were included in the study. Subjects were randomly allocated into either a pulsed
      radiofrequency treatment or a conventional transcutaneous electrical nerve
      stimulation treatment. All patients received exercise therapy. MAIN MEASUREMENTS:
      Outcome measurements were performed using the visual analogue scale for pain and
      range of motion; the Shoulder Pain and Disability Index was used for disability;
      and the Short Form-36 was used to establish quality of life. All of the
      measurements were assessed at four points in time (before the intervention, and
      for 1, 4 and 12 weeks afterwards). RESULTS: When the groups were compared, no
      significant difference was found between the groups in terms of visual analogue
      scale, range of motion, the Shoulder Pain and Disability Index (except for the
      Shoulder Pain and Disability Index total score), Short Form-36 subscores, and
      paracetamol consumption for all weeks (P >0.05). CONCLUSION: Our results showed
      that there is no difference in effect between transcutaneous electrical nerve
      stimulation and pulsed radiofrequency treatment for shoulder pain.

PMID- 20685722
TI  - Children with cerebral palsy: a systematic review and meta-analysis on gait and
      electrical stimulation.
AB  - OBJECTIVE: To conduct a systematic review and meta-analysis using the
      International Classification of Functioning to determine the summary effect of
      electrical stimulation on impairment and activity limitations relevant to gait
      problems of children with cerebral palsy. METHODS: We identified 40 cerebral
      palsy and electrical stimulation studies, and 17 gait studies qualified for
      inclusion. Applying enablement classification methods to walking abnormalities
      created two subgroups: impairment (N = 14) and activity limitations (N = 15).
      Overall, 238 participants experienced electrical stimulation treatments and 224
      served as a no stimulation control group. Calculations followed conventional data
      extraction and meta-analysis techniques: (a) individual standardized mean
      differences, (b) summary effect size, (c) I2 heterogeneity test, (d) fail-safe N
      analysis and (e) moderator variable analyses. RESULTS: Common outcome measures
      associated with impairment (n = 3) and activity limitations (n = 6) were
      submitted to separate random effects models meta-analyses, and revealed
      significant cumulative effect sizes: (a) impairment = 0.616 (SE = 0.10) and (b)
      activity limitations = 0.635 (SE = 0.14). I2 indicated low and medium amounts of
      dispersion, whereas fail-safe analyses revealed high N-values for both
      disablement categories. Moderator variable analyses further confirmed the
      positive treatment effects from both functional and neuromuscular stimulation.
      CONCLUSIONS: The present systematic review and meta-analyses determined medium
      effect sizes for electrical stimulation on walking impairment and activity
      limitations of children with cerebral palsy.

PMID- 20685723
TI  - Impact of enhanced secondary prevention on health behaviour in patients following
      minor stroke and transient ischaemic attack: a randomized controlled trial.
AB  - OBJECTIVE: To evaluate whether enhanced secondary prevention more significantly
      influences readiness to change health behaviour after minor stroke/transient
      ischaemic attack, compared with conventional stroke secondary prevention. DESIGN:
      Single-blind randomized control trial. SETTING: Rural district general hospital
      outpatient clinic. SUBJECTS: Fifteen women and 37 men with a mean age of 68.3
      years with first minor stroke or transient ischaemic attack. INTERVENTIONS: The
      intervention group received 'enhanced secondary prevention' (additional advice,
      motivational interviewing and telephone support) to change health behaviour. Both
      groups received 'conventional care' which included advice given during routine
      care. MAIN MEASURES: The primary outcome was 'readiness to change behaviour'
      measured using a validated stroke specific score based on the transtheoretical
      model. Secondary outcomes were the Hospital Anxiety and Depression Scale, and
      self-reported alcohol consumption, smoking behaviour, exercise frequency, and
      fruit and vegetable consumption. RESULTS: Analysis of the data for the 52
      participants showed no statistical difference in the groups for the primary
      outcome of readiness to change behaviour. Statistically significant improvements
      for change in self-reported exercise were demonstrated (P = 0.007); to 2-3 times
      per week in the intervention group compared to 0-1 times per week in the control
      group, and in fruit and vegetable consumption (P = 0.033); to 10 portions of
      fruit and vegetables consumed per week in the intervention group compared to 1 or
      2 portions a week for the control group. No evidence of a difference between
      groups was seen for alcohol consumption or Hospital Anxiety and Depression Scale.
      CONCLUSIONS: While no difference was demonstrated between the groups for
      readiness to change behaviour, a clinically significant effect in reported
      exercise behaviour and diet were demonstrated in the intervention group. This
      interesting finding indicates a dissonance between the behaviour scale and actual
      behaviour change, potentially indicating a lack of sensitivity of the scale to
      detect a change in this patient group.

PMID- 20685724
TI  - Psychosocial adjustment in children and adolescents with a parent with multiple
      sclerosis: a systematic review.
AB  - OBJECTIVE: This systematic review explored the potential impact of parental
      multiple sclerosis on their offspring. It considered adjustment to parental
      multiple sclerosis at different developmental stages and the factors associated
      with good versus poor adjustment. DATA SOURCES: MEDLINE, EMBASE, PsycINFO, CINAHL
      and Web of Science were searched for studies on children with a parent with
      multiple sclerosis. Inclusion and exclusion criteria were formulated. Hand
      searching journals and reference lists, contacting authors and multiple sclerosis
      societies for additional unpublished papers complemented the searches. REVIEW
      METHODS: Twenty studies that satisfied the inclusion criteria were included. The
      research articles were ranked according to a quality assessment checklist and
      were categorized as good, medium or poor quality. RESULTS: The review found good
      evidence to suggest that parental multiple sclerosis has a negative impact on
      children's social and family relationships and their psychological well-being.
      The review also identified potential factors associated with poor adjustment.
      These factors included parental negative emotions, increased illness severity,
      family dysfunction, children's lack of knowledge about the illness and lack of
      social support. Adolescent children also seemed to be more at risk for
      psychosocial problems than school-age children. CONCLUSIONS: There is good
      evidence that parental multiple sclerosis has a negative psychosocial impact on
      children, especially on adolescents.

PMID- 20685725
TI  - Active, passive and proprioceptive neuromuscular facilitation stretching are
      comparable in improving the knee flexion range in people with total knee
      replacement: a randomized controlled trial.
AB  - OBJECTIVE: To compare the immediate and medium-term effects of three stretching
      methods on the knee flexion range in people with a total knee replacement.
      DESIGN: Randomized clinical trial. SETTING: Rehabilitation hospital. SUBJECTS:
      117 patients were recruited and 100 (mean age: 68.43 +/- 7.95 years) of them
      completed the study. INTERVENTIONS: Patients receiving total knee replacement due
      to knee osteoarthritis were randomly assigned into 3 groups of: active stretching
      (group 1, n =32), passive stretching (group 2, n =35) and proprioceptive
      neuromuscular facilitation stretching (group 3, n =33). MAIN MEASURES: The
      immediate change in both active and passive knee flexion range after the first
      treatment session and the pattern of change in these ranges throughout the 2-week
      study period were compared among the three groups. RESULTS: All groups
      demonstrated significant improvement in knee ranges with time. The active range
      of group 1 improved by 19.9 degrees , group 2 by 25.3 degrees  and group 3 by
      22.5 degrees  throughout the 2-week period, whereas the improvements in the
      passive range were 18.8 degrees , 24.5 degrees  and 22.7 degrees , respectively.
      For between-group comparisons, no significant difference was found in both active
      (P = 0.647) and passive (P = 0.501) knee range immediately after stretching. For
      the changes at 2 weeks, there was also no significant difference among the groups
      in both active (P = 0.716) and passive (P = 0.959) knee ranges. CONCLUSION: This
      study revealed that all three modes of stretching were associated with an
      increase in the knee flexion range of patients after total knee replacement, with
      no statistically significant differences between the changes seen.

PMID- 20685726
TI  - The influence of tetrad shape and intersporal callose wall formation on pollen
      aperture pattern ontogeny in two eudicot species.
AB  - BACKGROUND AND AIMS: In flowering plants, microsporogenesis is accompanied by
      various types of cytoplasmic partitioning (cytokinesis). Patterns of male
      cytokinesis are suspected to play a role in the diversity of aperture patterns
      found in pollen grains of angiosperms. The relationships between intersporal wall
      formation, tetrad shape and pollen aperture pattern ontogeny are studied.
      METHODS: A comparative analysis of meiosis and aperture distribution was
      performed within tetrads in two triporate eudicot species with contrasting
      aperture arrangements within their tetrads [Epilobium roseum (Onagraceae) and
      Paranomus reflexus (Proteaceae)]. KEY RESULTS AND CONCLUSIONS: Intersporal wall
      formation is a two-step process in both species. Cytokinesis is first achieved by
      the formation of naked centripetal cell plates. These naked cell plates are then
      covered by additional thick, localized callose deposits that differ in location
      between the two species. Apertures are finally formed in areas in which
      additional callose is deposited on the cell plates. The recorded variation in
      tetrad shape is correlated with variations in aperture pattern, demonstrating the
      role of cell partitioning in aperture pattern ontogeny.

PMID- 20685727
TI  - Mycoheterotrophy evolved from mixotrophic ancestors: evidence in Cymbidium
      (Orchidaceae).
AB  - BACKGROUND AND AIMS: Nutritional changes associated with the evolution of
      achlorophyllous, mycoheterotrophic plants have not previously been inferred with
      robust phylogenetic hypotheses. Variations in heterotrophy in accordance with the
      evolution of leaflessness were examined using a chlorophyllous-achlorophyllous
      species pair in Cymbidium (Orchidaceae), within a well studied phylogenetic
      background. METHODS: To estimate the level of mycoheterotrophy in chlorophyllous
      and achlorophyllous Cymbidium, natural (13)C and (15)N contents (a proxy for the
      level of heterotrophy) were measured in four Cymbidium species and co-existing
      autotrophic and mycoheterotrophic plants and ectomycorrhizal fungi from two
      Japanese sites. KEY RESULTS: delta(13)C and delta(15)N values of the
      achlorophyllous C. macrorhizon and C. aberrans indicated that they are full
      mycoheterotrophs. delta(13)C and delta(15)N values of the chlorophyllous C.
      lancifolium and C. goeringii were intermediate between those of reference
      autotrophic and mycoheterotrophic plants; thus, they probably gain 30-50 % of
      their carbon resources from fungi. These data suggest that some chlorophyllous
      Cymbidium exhibit partial mycoheterotrophy (= mixotrophy). CONCLUSIONS: It is
      demonstrated for the first time that mycoheterotrophy evolved after the
      establishment of mixotrophy rather than through direct shifts from autotrophy to
      mycoheterotrophy. This may be one of the principal patterns in the evolution of
      mycoheterotrophy. The results also suggest that the establishment of symbiosis
      with ectomycorrhizal fungi in the lineage leading to mixotrophic Cymbidium served
      as pre-adaptation to the evolution of the mycoheterotrophic species. Similar
      processes of nutritional innovations probably occurred in several independent
      orchid groups, allowing niche expansion and radiation in Orchidaceae, probably
      the largest plant family.

PMID- 20685728
TI  - Underwater in situ measurements of radionuclides in selected submarine
      groundwater springs, Mediterranean Sea.
AB  - The application of the in situ measurement system 'KATERINA' for monitoring of
      radon progenies in submarine groundwater discharge (SGD) was investigated at
      different locations in the Mediterranean Sea (Chalkida, Stoupa, Korfos and
      Cabbe). At Chalkida and Stoupa radon progenies concentration exhibited almost
      constant values of 1.2 +/- 0.1 and 2.5 +/- 0.2 Bq l(-1), respectively. At Korfos
      these activities ranged between 1.4 +/- 0.1 and 2.3 +/- 0.2 Bq l(-1) exhibiting
      inverse relationship with salinity. At Cabbe the in situ measured data were
      compared with radon measurements obtained by liquid scintillation counter. The
      system also resolved radon progeny variations of SGD on time scales above 1 h.
      The radioactivity levels of radon progenies from all sites were found
      considerably lower (approximately 2 orders of magnitude) than the commonly
      accepted limits for radon in drinking water.

PMID- 20685729
TI  - Adverse events in a Tunisian hospital: results of a retrospective cohort study.
AB  - BACKGROUND: Despite the worldwide growing attention to patient safety, Tunisia
      has no data on the magnitude and consequences of hospital adverse events (AEs).
      OBJECTIVE: To estimate the incidence, nature and consequences of AEs and
      preventable AEs in a university hospital in Tunisia. DESIGN AND SETTING: We opted
      for a two-stage retrospective medical record review of 620 inpatients admitted
      during 2005 based on the use of 18 screening criteria. Records were reviewed by a
      trained medical student, then by an expert physician when one or more criteria
      were identified. Main outcomes measures We determine the incidence,
      preventability and consequences of the AEs. Patients and admissions
      characteristics were also recorded. RESULTS: Among 620 inpatients, 62 inpatients
      experienced an AE with an incidence of 10% (95% CI [7.6-12.3]). Surgical/invasive
      procedures and therapeutic errors were the most common AEs (55 and 21%,
      respectively). Among the confirmed events 60% were judged to be highly
      preventable and 21% led to patient death. All ages and both genders experienced
      equal rates of AEs. However, patients who experienced these events were
      significantly more exposed to extrinsic risk factors (all surgical interventions
      and invasive procedures that were listed in the revue form 2 of the
      questionnaire). Physician reviewers estimated that a total of 570 additional
      hospital days were associated with AEs. CONCLUSION: This study confirms that
      preventable AEs were not rare in our context. They caused human harm and consumed
      a significant part of hospital resources. Thus, targeted interventions are
      needed.

PMID- 20685730
TI  - Involvement of brassinosteroid signals in the floral-induction network of
      Arabidopsis.
AB  - The transition to flowering is known to be regulated by numerous interacting
      endogenous and environmental cues, of which brassinosteroids (BRs), a group of
      polyhydroxylated steroid phytohormones, appear to be linked to the regulation of
      flowering time. In Arabidopsis, BR biosynthetic det2 mutants exhibited delayed
      flowering time by at least 10 d compared with the wild type. The levels of
      endogenous BRs in det2 were below 10% of the wild type. The timing of flowering
      was also delayed in the BR biosynthetic dwf4 and cpd mutants and in the BR
      insensitive bri1 mutants. Because brassinolide (BL) and different BL precursors
      were over-accumulated in BR biosynthetic mutants and BR-insensitive bri1 mutants,
      this showed that alterations in the endogenous BL content and the level of
      different BL precursors affect flowering time in Arabidopsis. The late-flowering
      phenotypes of bri1 also showed that components of the BR signal transduction
      pathway affect flowering time. So far, reports on a connection between BRs and
      flowering time are limited. This review summarizes recent advances regarding the
      action of BRs in the transition to flowering.

PMID- 20685731
TI  - The impact of drought on leaf physiology of Quercus suber L. trees: comparison of
      an extreme drought event with chronic rainfall reduction.
AB  - Understanding the responses of cork oak (Quercus suber L.) to actual and
      predicted summer conditions is essential to determine the future sustainability
      of cork oak woodlands in Iberia. Thermal imaging may provide a rapid method for
      monitoring the extent of stress. The ecophysiology of cork trees was studied over
      three years. Three treatments were applied by means of rainfall capture and
      irrigation, with plots receiving 120%, 100%, or 80% of natural precipitation.
      Despite stomatal closure, detected using both thermal imaging and porometry, leaf
      water potential fell during the summer, most drastically during the third year of
      accumulative stress. The quantum efficiency (PhiPSII) and the maximum efficiency
      Fv' /FM' of photosystem II also fell more intensely over the third summer, while
      non-photochemical quenching (NPQ) increased. The reduced precipitation treatment
      sporadically further reduced leaf water potential, stomatal conductance (gs), IG
      (an index of gs derived from thermal imaging), PhiPSII, and Fv' /FM', and
      increased leaf temperature and NPQ. It is concluded that these are very resilient
      trees since they were only severely affected in the third year of severe drought
      (the third year registering 45% less rainfall than average), and removing 20% of
      rainfall had a limited impact..

PMID- 20685732
TI  - Kctd15 inhibits neural crest formation by attenuating Wnt/beta-catenin signaling
      output.
AB  - Neural crest (NC) precursors are stem cells that are capable of forming many cell
      types after migration to different locations in the embryo. NC and placodes form
      at the neural plate border (NPB). The Wnt pathway is essential for specifying NC
      versus placodal identity in this cell population. Here we describe the BTB domain
      containing protein Potassium channel tetramerization domain containing 15
      (Kctd15) as a factor expressed in the NPB that efficiently inhibits NC induction
      in zebrafish and frog embryos. Whereas overexpression of Kctd15 inhibited NC
      formation, knockdown of Kctd15 led to expansion of the NC domain. Likewise, NC
      induction by Wnt3a plus Chordin in Xenopus animal explants was suppressed by
      Kctd15, but constitutively active beta-catenin reversed Kctd15-mediated
      suppression of NC induction. Suppression of NC induction by inhibition of Wnt8.1
      was rescued by reduction of Kctd15 expression, linking Kctd15 action to the Wnt
      pathway. We propose that Kctd15 inhibits NC formation by attenuating the output
      of the canonical Wnt pathway, thereby restricting expansion of the NC domain
      beyond its normal range.

PMID- 20685733
TI  - In vivo evidence for transdifferentiation of peripheral neurons.
AB  - It is commonly thought that differentiated neurons do not give rise to new cells,
      severely limiting the potential for regeneration and repair of the mature nervous
      system. However, we have identified cells in zebrafish larvae that first
      differentiate into dorsal root ganglia sensory neurons but later acquire a
      sympathetic neuron phenotype. These transdifferentiating neurons are present in
      wild-type zebrafish. However, they are increased in number in larvae that have a
      mutant voltage-gated sodium channel gene, scn8aa. Sodium channel knock-down
      promotes migration of differentiated sensory neurons away from the ganglia. Once
      in a new environment, sensory neurons transdifferentiate regardless of sodium
      channel expression. These findings reveal an unsuspected plasticity in
      differentiated neurons that points to new strategies for treatment of nervous
      system disease.

PMID- 20685734
TI  - Notch regulates the switch from symmetric to asymmetric neural stem cell division
      in the Drosophila optic lobe.
AB  - The proper balance between symmetric and asymmetric stem cell division is crucial
      both to maintain a population of stem cells and to prevent tumorous overgrowth.
      Neural stem cells in the Drosophila optic lobe originate within a polarised
      neuroepithelium, where they divide symmetrically. Neuroepithelial cells are
      transformed into asymmetrically dividing neuroblasts in a precisely regulated
      fashion. This cell fate transition is highly reminiscent of the switch from
      neuroepithelial cells to radial glial cells in the developing mammalian cerebral
      cortex. To identify the molecules that mediate the transition, we microdissected
      neuroepithelial cells and compared their transcriptional profile with similarly
      obtained optic lobe neuroblasts. We find genes encoding members of the Notch
      pathway expressed in neuroepithelial cells. We show that Notch mutant clones are
      extruded from the neuroepithelium and undergo premature neurogenesis. A wave of
      proneural gene expression is thought to regulate the timing of the transition
      from neuroepithelium to neuroblast. We show that the proneural wave transiently
      suppresses Notch activity in neuroepithelial cells, and that inhibition of Notch
      triggers the switch from symmetric, proliferative division, to asymmetric,
      differentiative division.

PMID- 20685735
TI  - Wnt signaling promotes oral but suppresses aboral structures in Hydractinia
      metamorphosis and regeneration.
AB  - We studied the role of Wnt signaling in axis formation during metamorphosis and
      regeneration in the cnidarian Hydractinia. Activation of Wnt downstream events
      during metamorphosis resulted in a complete oralization of the animals and
      repression of aboral structures (i.e. stolons). The expression of Wnt3, Tcf and
      Brachyury was upregulated and became ubiquitous. Rescue experiments using Tcf
      RNAi resulted in normal metamorphosis and quantitatively normal Wnt3 and
      Brachyury expression. Isolated, decapitated polyps regenerated only heads but no
      stolons. Activation of Wnt downstream targets in regenerating animals resulted in
      oralization of the polyps. Knocking down Tcf or Wnt3 by RNAi inhibited head
      regeneration and resulted in complex phenotypes that included ectopic aboral
      structures. Multiple heads then grew when the RNAi effect had dissipated. Our
      results provide functional evidence that Wnt promotes head formation but
      represses the formation of stolons, whereas downregulation of Wnt promotes
      stolons and represses head formation.

PMID- 20685736
TI  - Planar polarity of multiciliated ependymal cells involves the anterior migration
      of basal bodies regulated by non-muscle myosin II.
AB  - Motile cilia generate constant fluid flow over epithelial tissue, and thereby
      influence diverse physiological processes. Such functions of ciliated cells
      depend on the planar polarity of the cilia and on their basal bodies being
      oriented in the downstream direction of fluid flow. Recently, another type of
      basal body planar polarity, characterized by the anterior localization of the
      basal bodies in individual cells, was reported in the multiciliated ependymal
      cells that line the surface of brain ventricles. However, little is known about
      the cellular and molecular mechanisms by which this polarity is established.
      Here, we report in mice that basal bodies move in the apical cell membrane during
      differentiation to accumulate in the anterior region of ependymal cells. The
      planar cell polarity signaling pathway influences basal body orientation, but not
      their anterior migration, in the neonatal brain. Moreover, we show by
      pharmacological and genetic studies that non-muscle myosin II is a key regulator
      of this distribution of basal bodies. This study demonstrates that the
      orientation and distribution of basal bodies occur by distinct mechanisms.

PMID- 20685738
TI  - Live and let die: is neutrophil apoptosis defective in severe asthma?

PMID- 20685737
TI  - BMPs and FGFs target Notch signalling via jagged 2 to regulate tooth
      morphogenesis and cytodifferentiation.
AB  - The Notch signalling pathway is an evolutionarily conserved intercellular
      signalling mechanism that is essential for cell fate specification and proper
      embryonic development. We have analysed the expression, regulation and function
      of the jagged 2 (Jag2) gene, which encodes a ligand for the Notch family of
      receptors, in developing mouse teeth. Jag2 is expressed in epithelial cells that
      give rise to the enamel-producing ameloblasts from the earliest stages of tooth
      development. Tissue recombination experiments showed that its expression in
      epithelium is regulated by mesenchyme-derived signals. In dental explants
      cultured in vitro, the local application of fibroblast growth factors upregulated
      Jag2 expression, whereas bone morphogenetic proteins provoked the opposite
      effect. Mice homozygous for a deletion in the Notch-interaction domain of Jag2
      presented a variety of severe dental abnormalities. In molars, the crown
      morphology was misshapen, with additional cusps being formed. This was due to
      alterations in the enamel knot, an epithelial signalling structure involved in
      molar crown morphogenesis, in which Bmp4 expression and apoptosis were altered.
      In incisors, cytodifferentiation and enamel matrix deposition were inhibited. The
      expression of Tbx1 in ameloblast progenitors, which is a hallmark for ameloblast
      differentiation and enamel formation, was dramatically reduced in Jag2(-/-)
      teeth. Together, these results demonstrate that Notch signalling mediated by Jag2
      is indispensable for normal tooth development.

PMID- 20685739
TI  - British Thoracic Society Pleural Disease Guidelines--2010 update.

PMID- 20685740
TI  - Altered matrix production in the distal airways of individuals with asthma.
AB  - BACKGROUND AND AIMS: Although increasing evidence suggests involvement of the
      distal airway in all stages of asthma, it is not known whether structural changes
      (defined as airway remodelling) occur in the distal airways of subjects with mild
      asthma and those with atopy. The aim of this study was to compare control
      subjects and those with mild asthma in relation to fibroblast phenotypes and
      remodelling in central and distal airways. METHODS: Distal and central
      fibroblasts from controls (n=12) and patients with mild asthma (n=11) were
      cultured and incubated for 24 h with 0.4% serum, or stimulated with transforming
      growth factor beta1 (TGFbeta1). [(35)S]Sulfate-labelled proteoglycans in culture
      medium were analysed by ion exchange chromatography and sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. Proliferation was measured with crystal
      violet, and exhaled nitric oxide was measured by the fractional nitric oxide
      technique. RESULTS: Vesican production from distal fibroblasts was significantly
      elevated in patients with asthma compared with controls (p<0.001), and the
      percentage collagen-positive area in distal asthma tissue was also enhanced
      compared with controls (p<0.01). In addition, distal asthma fibroblasts had
      reduced proliferation capacity compared with those of controls (by 24%; p<0.01).
      Furthermore, the alveolar nitric oxide concentration was correlated to distal
      biglycan and perlecan production of subjects with asthma (r=-0.857, p<0.05 and r=
      0.750, p<0.05 respectively) CONCLUSION: It is shown that centrally and distally
      derived fibroblasts differ in their proteoglycan production and proliferation
      between central and distal tissue, and in those with asthma compared with
      controls. It is also demonstrated that remodelling is present in distal lung of
      subjects with mild asthma. This may be of importance in airway remodelling and
      asthma progression.

PMID- 20685741
TI  - Prosurvival activity for airway neutrophils in severe asthma.
AB  - BACKGROUND: Airway neutrophilia is a recognised feature of chronic severe asthma,
      but the mechanisms that underlie this phenomenon are unknown. Evidence for
      factors present in airway secretions that prolong neutrophil survival has been
      sought and it has been hypothesised that these might be augmented in neutrophilic
      asthma. METHODS: Non-smoking subjects with severe asthma (SA) or mild asthma (MA)
      and healthy control subjects (HC) underwent sputum induction. The SA group was
      subdivided into subjects with neutrophil counts above (SA-high) and those within
      the normal range (SA-low). Apoptotic neutrophils were enumerated in the cellular
      phase while the fluid phase was assessed for its ability to prolong the in vitro
      survival of blood-derived neutrophils using morphometric and flow cytometric
      analyses. RESULTS: There was a significant difference between all four subject
      groups with respect to the percentage of apoptotic sputum neutrophils (Kruskal
      Wallis, p=0.042). Cuzick test showed a highly significant (p=0.008) trend towards
      decreasing numbers of apoptotic neutrophils across the four groups with
      increasing asthma severity and neutrophil count. The sputum antiapoptotic
      activity was also different between the groups (p=0.039), with a highly
      significant (p=0.005) decreasing trend across the four groups. The survival
      effect could not be inhibited by blocking selective chemotaxin receptors,
      neutralising neutrophil survival factors, inhibiting phosphatidylinositol-3
      kinase (using LY294002) or with pertussis toxin pretreatment. Similarly, it could
      not be explained by lipopolysaccharide contamination or by the presence of
      inhaled corticosteroids in sputum. CONCLUSIONS: These data demonstrate the
      capacity of as yet unidentified factor(s) in the airways of subjects with asthma
      to delay human neutrophil apoptosis and extend their lifespan as a potential
      mechanism contributing to unresolving airways neutrophilia in severe asthma.

PMID- 20685742
TI  - Toll-like receptor 2 and 4 genes influence susceptibility to adverse effects of
      traffic-related air pollution on childhood asthma.
AB  - BACKGROUND: Epidemiological studies have reported adverse effects of ambient air
      pollution on the prevalence of asthma. Laboratory studies have suggested that
      innate immune responses are involved. OBJECTIVE: A study was undertaken to
      determine whether the Toll-like receptor 2 and 4 genes (TLR2 and TLR4) influence
      the susceptibility to adverse effects of traffic-related air pollution with
      respect to the prevalence of childhood asthma. METHODS: Haplotype tagging single
      nucleotide polymorphisms (SNPs) in the TLR2 (n=4) and TLR4 genes (n=9) were
      genotyped in 916 children from the Prevention and Incidence of Asthma and Mite
      Allergy (PIAMA) birth cohort. Exposure to particulate matter (PM(2.5)), soot and
      nitrogen dioxide (NO(2)) at the birth address was estimated by land use
      regression models. Interactions between levels of pollutants and SNPs in relation
      to annual questionnaire reports of asthma diagnosis and symptoms from birth up to
      8 years of age were analysed longitudinally by generalised estimating equations.
      RESULTS: Two TLR2 SNPs and four TLR4 SNPs significantly modified the effect of
      air pollution on the prevalence of doctor-diagnosed asthma from birth up to 8
      years of age. The risk of having doctor-diagnosed asthma increased with
      increasing PM(2.5) levels in children with at least one copy of the TLR2
      rs4696480 A allele (OR 2.0 (95% CI 1.2 to 3.1) for an interquartile range
      increase in exposure). Similar observations were present with the following TLR4
      genotypes: rs2770150 TC (OR 2.0 (95% CI 1.1 to 3.6)), rs10759931 GG (OR 2.6 (95%
      CI 1.4 to 4.9)), rs6478317 GG (OR 2.2 (95% CI 1.2 to 4.3)), rs10759932 CT or CC
      (OR 2.9 (95% CI 1.2 to 6.9)) and rs1927911 TT (OR 4.4 (95% CI 1.7 to 11.7)).
      CONCLUSIONS: Variant alleles of TLR2 and TLR4 genes influence the susceptibility
      to adverse effects of traffic-related air pollution on childhood asthma.

PMID- 20685743
TI  - Risk of invasive pneumococcal infections among working age adults with asthma.
AB  - BACKGROUND: Information about the risk of invasive pneumococcal infection (IPI)
      among adults with asthma is limited and inconsistent. To evaluate this
      association, a population-based case-control study was conducted. METHODS: Cases
      of IPI (Streptococcus pneumoniae isolated from blood or cerebrospinal fluid) were
      identified through national, population-based laboratory surveillance during 1995
      2002. To maximise exclusion of chronic obstructive pulmonary disease, the
      analysis was limited to patients aged 18-49 years and 10 selected age-, sex- and
      health district-matched controls for each case from the Population Information
      System. Information on underlying medical conditions was obtained through linking
      surveillance data to other national health registries. Asthma requiring > or =1
      hospitalisation in the past 12 months was defined as high risk asthma (HRA); low
      risk asthma (LRA) was defined as entitlement to prescription drug benefits and no
      hospitalisation for asthma in the past 12 months. RESULTS: 1282 patients with IPI
      and 12 785 control subjects were identified. Overall, 7.1% of cases and 2.5% of
      controls had asthma (6.0% and 2.4% had LRA whereas 1.1% and 0.1% had HRA,
      respectively. After adjustment for other independent risk factors in a
      conditional logistic regression model, IPI was associated with both LRA (matched
      OR (mOR) 2.8; 95% CI 2.1 to 3.6) and HRA (mOR, 12.3; 95% CI 5.4 to 28.0). The
      adjusted population-attributable risk was 0.039 (95% CI 0.023 to 0.055) for LRA
      and 0.01 (95% CI 0.0035 to 0.017) for HRA. CONCLUSIONS: Working age adults with
      asthma are at increased risk of IPI. In this population, approximately 5% of
      disease burden could be attributed to asthma. These findings support adding
      medicated asthma in adults to the list of indications for pneumococcal
      vaccination.

PMID- 20685744
TI  - Quorum sensing-dependent virulence during Pseudomonas aeruginosa colonisation and
      pneumonia in mechanically ventilated patients.
AB  - BACKGROUND: Pseudomonas aeruginosa frequently colonises intubated patients and
      causes life-threatening ventilator-associated pneumonia (VAP). The role of quorum
      sensing (QS), regulating virulence in this pathogen, during colonisation and
      development of VAP is unknown. METHODS: P aeruginosa isolates and tracheal
      aspirates were prospectively collected from intubated patients. Genotypes and QS
      independent virulence traits (exoU, exoS, PAPI-1 and PAPI-2) harboured by
      colonising isolates were identified in vitro with the CLONDIAG array. The
      production of elastase and rhamnolipids was measured to assess QS-dependent
      virulence. To monitor QS activity 'in patient', total RNA was extracted directly
      from tracheal aspirates and expression of QS genes was measured. RESULTS: 320 P
      aeruginosa isolates and tracheal aspirates were obtained from 29 patients of whom
      6 developed VAP (20%). Seven patients (24%) were initially colonised by QS
      proficient isolates; 57% of them developed VAP as compared with 9% of patients
      colonised by QS-deficient isolates (p=0.018). Of all tested virulence traits from
      the initial colonising isolates, only rhamnolipids were associated with
      development of VAP (p=0.003). VAP occurred more frequently in patients colonised
      during the entire observation period by isolates producing high levels of
      rhamnolipids (p=0.001). 'In patient' monitoring of QS genes showed non-induced
      expression profiles in patients without VAP. In contrast, exponential induction
      of QS circuit and target gene expression was observed for two patients with VAP,
      and an 'in patient' QS gene expression profile and hierarchy similar to those in
      vitro was measured for one patient with VAP. CONCLUSIONS: Production of the QS
      dependent virulence factor rhamnolipids by colonising P aeruginosa isolates is
      associated with development of VAP.

PMID- 20685746
TI  - Long-term effectiveness and cost-effectiveness of smoking cessation interventions
      in patients with COPD.
AB  - BACKGROUND: The aim of this study was to estimate the long-term (cost-)
      effectiveness of smoking cessation interventions for patients with chronic
      obstructive pulmonary disease (COPD). METHODS: A systematic review was performed
      of randomised controlled trials on smoking cessation interventions in patients
      with COPD reporting 12-month biochemical validated abstinence rates. The
      different interventions were grouped into four categories: usual care, minimal
      counselling, intensive counselling and intensive counselling + pharmacotherapy
      ('pharmacotherapy'). For each category the average 12-month continuous abstinence
      rate and intervention costs were estimated. A dynamic population model for COPD
      was used to project the long-term (cost-) effectiveness (25 years) of 1-year
      implementation of the interventions for 50% of the patients with COPD who smoked
      compared with usual care. Uncertainty and one-way sensitivity analyses were
      performed for variations in the calculation of the abstinence rates, the type of
      projection, intervention costs and discount rates. RESULTS: Nine studies were
      selected. The average 12-month continuous abstinence rates were estimated to be
      1.4% for usual care, 2.6% for minimal counselling, 6.0% for intensive counselling
      and 12.3% for pharmacotherapy. Compared with usual care, the costs per quality
      adjusted life year (QALY) gained for minimal counselling, intensive counselling
      and pharmacotherapy were euro 16 900, euro 8200 and euro 2400, respectively. The
      results were most sensitive to variations in the estimation of the abstinence
      rates and discount rates. CONCLUSION: Compared with usual care, intensive
      counselling and pharmacotherapy resulted in low costs per QALY gained with ratios
      comparable to results for smoking cessation in the general population. Compared
      with intensive counselling, pharmacotherapy was cost saving and dominated the
      other interventions.

PMID- 20685748
TI  - Cardiovascular events in patients with COPD: TORCH study results.
AB  - BACKGROUND: Previous studies have suggested that long-term use of beta agonists
      to treat chronic obstructive pulmonary disease (COPD) may increase the risk of
      cardiovascular adverse events. In this post hoc analysis, data from the TOwards a
      Revolution in COPD Health (TORCH) study were used to investigate whether use of
      the long-acting beta(2) agonist salmeterol over 3 years increased the risk of
      cardiovascular adverse events in patients with moderate to severe COPD. METHODS:
      TORCH was a randomised, double-blind, placebo controlled study conducted at 444
      centres in 42 countries. Patients (n=6184; safety population) received twice
      daily combined salmeterol 50 microg plus fluticasone propionate 500 microg (SFC),
      either component alone, or placebo. Adverse events were recorded every 12 weeks
      for 3 years. RESULTS: The probability of having a cardiovascular adverse event by
      3 years was 24.2% for placebo, 22.7% for salmeterol, 24.3% for fluticasone
      propionate and 20.8% for SFC. Although a history of myocardial infarction doubled
      the probability of cardiovascular adverse events, the event rates remained
      similar across treatment groups. CONCLUSION: Post hoc analysis of the 3-year
      TORCH dataset showed that salmeterol alone or in combination (SFC) did not
      increase the risk of cardiovascular events in patients with moderate to severe
      COPD.

PMID- 20685749
TI  - The effect of mandibular advancement on upper airway structure in obstructive
      sleep apnoea.
AB  - BACKGROUND: The mechanisms by which mandibular advancement splints (MAS) improve
      obstructive sleep apnoea (OSA) are not well understood. This study aimed to
      evaluate the mechanism of action of MAS by assessing their effect on upper airway
      structure in patients with OSA. METHODS: Patients were recruited from a sleep
      disorders clinic for treatment with a custom-made MAS. MRI of the upper airway
      was performed during wakefulness in the supine position, with and without the
      MAS. RESULTS: Sixty-nine patients with OSA were recruited. Treatment with the MAS
      reduced the apnoea-hypopnoea index (AHI) from 27.0+/-14.7 events/h to 12.2+/-12.5
      events/h (p<0.001). There was an increase in the total airway volume with
      mandibular advancement (16.5+/-0.7 cm(3) vs 18.1+/-0.8 cm(3); p<0.01) that
      occurred predominantly because of an increase in the volume of the velopharynx
      (5.7+/-0.3 cm(3) vs 6.5+/-0.3 cm(3); p<0.001). This increase in airway calibre
      was associated with an increase in the lower anterior facial height (6.8+/-0.1 cm
      vs 7.5+/-0.1 cm; p<0.001), reduction in the distance between the hyoid and
      posterior nasal spine (7.4+/-0.1 cm vs 7.2+/-0.1 cm; p<0.001), lateral
      displacement of the parapharyngeal fat pads away from the airway (right
      parapharyngeal fat pad 0.17+/-0.02 cm; left parapharyngeal fat pad 0.22+/-0.02
      cm) and anterior movement of the tongue base muscles (0.33+/-0.03 cm).
      Subanalyses in responders and non-responders to MAS treatment showed that the
      increase in upper airway calibre with mandibular advancement occurred only in
      responders. CONCLUSION: These results suggest that the mechanism of action of MAS
      is to increase the volume of the upper airway, predominantly by increasing the
      volume of the velopharynx, and this increased volume is associated with changes
      in the surrounding bony and soft tissue structures.

PMID- 20685750
TI  - NOX4/NADPH oxidase expression is increased in pulmonary fibroblasts from patients
      with idiopathic pulmonary fibrosis and mediates TGFbeta1-induced fibroblast
      differentiation into myofibroblasts.
AB  - BACKGROUND: Persistence of myofibroblasts is believed to contribute to the
      development of fibrosis in idiopathic pulmonary fibrosis (IPF). Transforming
      growth factor beta1 (TGFbeta1) irreversibly converts fibroblasts into
      pathological myofibroblasts, which express smooth muscle alpha-actin (alpha-SMA)
      and produce extracellular matrix proteins, such as procollagen I (alpha1).
      Reactive oxygen species produced by NADPH oxidases (NOXs) have been shown to
      regulate cell differentiation. It was hypothesised that NOX could be expressed in
      parenchymal pulmonary fibroblasts and could mediate TGFbeta1-stimulated
      conversion of fibroblasts into myofibroblasts. METHODS: Fibroblasts were cultured
      from the lung of nine controls and eight patients with IPF. NOX4, alpha-SMA and
      procollagen I (alpha1) mRNA and protein expression, reactive oxygen species
      production and Smad2/3 phosphorylation were quantified, in the absence and in the
      presence of incubation with TGFbeta1. Migration of platelet-derived growth factor
      (PDGF)-induced fibroblasts was also assessed. RESULTS: It was found that (1) NOX4
      mRNA and protein expression was upregulated in pulmonary fibroblasts from
      patients with IPF and correlated with mRNA expression of alpha-SMA and
      procollagen I (alpha1) mRNA; (2) TGFbeta1 upregulated NOX4, alpha-SMA and
      procollagen I (alpha1) expression in control and IPF fibroblasts; (3) the change
      in alpha-SMA and procollagen I (alpha1) expression in response to TGFbeta1 was
      inhibited by antioxidants and by a NOX4 small interfering RNA (siRNA); (4) NOX4
      modulated alpha-SMA and procollagen I (alpha1) expression by controlling
      activation of Smad2/3; and (5) NOX4 modulated PDGF-induced fibroblast migration.
      CONCLUSION: NOX4 is critical for modulation of the pulmonary myofibroblast
      phenotype in IPF, probably by modulating the response to TGFbeta1 and PDGF.

PMID- 20685751
TI  - SMAD4 mutation and the combined syndrome of juvenile polyposis syndrome and
      hereditary haemorrhagic telangiectasia.
AB  - Juvenile polyposis syndrome (JPS) and hereditary haemorrhagic telangiectasia
      (HHT) are autosomal dominant disorders with characteristic clinical phenotypes.
      Recently, reports of the combined syndrome of JPS and HHT have been described in
      individuals with mutations in the SMAD4 gene, whose product-SMAD4-is a critical
      intracellular effector in the signalling pathway of transforming growth factor
      beta (TGFbeta). This report describes a 24-year-old man who presented to the
      Respiratory Institute after colectomy for JPS with a SMAD4 mutation and who was
      subsequently diagnosed to have HHT with asymptomatic cerebral and pulmonary
      arteriovenous malformations (AVMs). Patients with JPS due to a SMAD4 mutation
      should be screened for the vascular lesions associated with HHT, especially
      occult AVMs in visceral organs, which may potentially present catastrophically
      with serious medical consequences.

PMID- 20685752
TI  - The impact of polymyxin B dosage on in-hospital mortality of patients treated
      with this antibiotic.
AB  - OBJECTIVE: To assess the impact of dosage on in-hospital mortality of patients
      receiving intravenous polymyxin B. METHODS: A retrospective cohort study was
      performed from January 2003 to December 2009. Patients >= 18 years receiving
      intravenous polymyxin B for >= 72 h were analysed. Clinical covariates were
      assessed and data were retrieved from medical records. Subgroup analyses were
      performed in patients with microbiologically confirmed infections and in patients
      with bacteraemia. Renal toxicity was also assessed. Logistic regression models
      (LRMs) were performed for the entire cohort and subgroups. RESULTS: A total of
      276 patients were included. The overall in-hospital mortality was 60.5% (167 of
      276). The final LRM showed that severe sepsis or septic shock [adjusted odds
      ratio (aOR) 4.07; 95% confidence interval (CI) 2.22-7.46], presence of mechanical
      ventilation (aOR 3.14; 95% CI 1.73-5.71), Charlson co-morbidity score (aOR 1.25;
      95% CI 1.09-1.44) and age (aOR 1.02; 95% CI 1.01-1.04) were independently
      associated with increased in-hospital mortality, while >= 200 mg/day polymyxin B
      was associated with lower risk for this outcome (aOR 0.43; 95% CI 0.23-0.79). The
      effect of >= 200 mg/day polymyxin B on in-hospital mortality was higher in both
      subgroups (microbiologically documented infections and bacteraemia). Patients
      receiving >= 200 mg/day of polymyxin B had significantly higher risk of severe
      renal impairment. CONCLUSION: A dosage of >= 200 mg/day polymyxin B was
      associated with lower in-hospital mortality. The benefit of these higher doses
      outweighed the risk of severe renal dysfunction during therapy. Large prospective
      studies including pharmacokinetic/pharmacodynamic analysis are still required to
      define the best dosage regimens of polymyxin B.

PMID- 20685753
TI  - Zone breakpoints, by the CLSI disc method, for 15 MUg tigecycline discs
      corresponding to EUCAST MIC breakpoints.

PMID- 20685754
TI  - Emergence of an IncIgamma plasmid encoding CMY-2 beta-lactamase associated with
      the international ST19 OXA-30-producing beta-lactamase Salmonella Typhimurium
      multidrug-resistant clone.
AB  - OBJECTIVES: To analyse the genetic environment of the bla(CMY-2) gene in a
      multidrug-resistant isolate belonging to the OXA-30-producing Salmonella enterica
      serotype Typhimurium clone widespread in European countries. METHODS: Preliminary
      characterization of CMY-2 was performed after determining the phenotype against
      beta-lactams, the pI (isoelectric focusing) and the presence of bla genes (PCR).
      The genetic context of the bla(CMY-2) gene was identified by PCR mapping and
      further sequencing. Plasmid analysis included determination of transferability,
      size and content (S1-PFGE/hybridization), and characterization of the
      incompatibility group (PCR-based replicon typing, hybridization and sequencing).
      RESULTS: The DeltaISEcp1-bla(CMY-2)-blc-sugE cassette identified is located in
      the pndC-trbA region of an IncIgamma conjugative plasmid designated pSTHV23035.
      This plasmid differs from previously described European IncI plasmids coding for
      CMY in the IncI replicon type and in the integration site of the element carrying
      bla(CMY-2). CONCLUSIONS: The emergence of bla(CMY-2) located in a new IncIgamma
      plasmid in an isolate belonging to the international widespread multidrug
      resistant sequence type (ST) 19 OXA-30-producing Salmonella Typhimurium clone is
      reported for the first time. Acquisition of a new bla(CMY-2)-IncIgamma plasmid by
      Salmonella multidrug-resistant strains is of concern since these plasmids
      diminish the activity of therapeutically important broad-spectrum beta-lactams
      and contribute to the persistence and pathogenicity of widespread clones.

PMID- 20685755
TI  - The deregulation of regulatory T cells on interleukin-17-producing T helper cells
      in patients with unexplained early recurrent miscarriage.
AB  - BACKGROUND: CD4(+)CD25(+) regulatory T cells (Tregs) are important for the
      maintenance of immune homeostasis by virtue of their ability to control T-cell
      proliferation in the peripheral blood (PB). We recently demonstrated that the
      prevalence of Tregs is decreased, whereas that of Th17 cells is increased, in the
      PB and decidua samples of patients with unexplained recurrent miscarriage (RM).
      In this study, we investigated whether the cytokine production of Th17 cells can
      be suppressed by the Tregs and elucidated the mechanism by which Tregs exert this
      suppressive effect. METHODS: Flow cytometry was used to analyze the surface
      phenotype and cytokine production of Th17 cells in the PB of women with
      unexplained RM (n = 17) and healthy women in early stages of pregnancy who
      underwent elective abortion (n = 20). The suppressive ability of Tregs on Th17
      cells was assessed in in vitro co-cultures and transwell experiments. The amount
      of secreted interleukin-17 (IL-17) in the supernatants was measured by enzyme
      linked immunosorbent assay (ELISA). The inhibitory activity of transforming
      growth factor-beta (TGF-beta) and IL-10 on IL-17 expression in CD4(+) T cells was
      assessed using ELISA. RESULTS: The proportions of IL-17-positive CD4(+) T cells,
      CC chemokine receptor type 6 (CCR6)-positive CD4(+) T cells and CCR6 expression
      of IL-17-positive CD4(+) T cells were higher in the PB samples of patients with
      unexplained RM than in PB of healthy control subjects. In vitro, Tregs could
      inhibit the expression of IL-17; more Th17 cells were inhibited in the control
      group than in the unexplained RM group. High-dose TGF-beta inhibited the
      expression of IL-17, whereas IL-10 inhibited IL-17 expression in a dose-dependent
      manner. CONCLUSIONS: IL-17 expression can be inhibited by Tregs. The suppressive
      activity of Tregs on Th17 cells was decreased in patients with unexplained RM.
      The ability of Tregs to suppress cytokine secretion might be effected by a cell
      cell contact. TGF-beta and IL-10 could inhibit the expression of IL-17.

PMID- 20685757
TI  - Sexual violence, HSV-2 and HIV are important predictors for infertility in
      Rwanda.
AB  - BACKGROUND: In order to formulate cost-effective health interventions aimed at
      preventing infertility it is necessary to identify modifiable risk factors for
      infertility in sub-Saharan Africa. This case-control study examined potential
      predictors and their population attributable fraction (PAF%) for various
      infertility types including lifestyle factors, sexual behaviour and reproductive
      tract infections (RTIs). METHODS: Sexually active women aged 21-45 year
      presenting with infertility problems at the infertility clinic of the Kigali
      University Teaching Hospital (n = 312), and fertile controls who recently
      delivered (n = 283) were surveyed together with their male partners. Participants
      were interviewed about socio-demographic characteristics, sexual behaviours and
      lifestyle factors, and were tested for HIV and RTIs. RESULTS: Variables
      significantly associated with tubal infertility were history of sexual violence
      [adjusted odds ratio (AOR) 2.41; 95% CI 1.36-4.25]; positive HIV (AOR 2.41; 95%
      CI 1.36-4.25), herpes simplex virus type 2 (HSV-2; AOR 1.67; 95% CI 1.03-2.71)
      and Chlamydia trachomatis serology (AOR 1.78; 95% CI 0.99-3.21), and current
      bacterial vaginosis by Amsel criteria (AOR 1.97; 95% CI 1.12-3.47). Among men,
      male factor infertility was associated with positive HIV (AOR 2.43; 95% CI 1.31
      5.23) and HSV-2 serology (AOR 1.71; 95% CI 1.02-2.87) and current urologic
      abnormalities (AOR 2.38; 95% CI 1.01-5.31). Positive HSV-2 serostatus carried the
      greatest PAF% (26%) for tubal infertility, followed by positive HIV serostatus
      (20%) and history of sexual violence (17%). CONCLUSIONS: Although temporal
      relationships are difficult to ascertain, history of sexual violence, HSV-2
      infection and HIV infection are important predictors of infertility in Rwanda.

PMID- 20685756
TI  - Incorrect DNA methylation of the DAZL promoter CpG island associates with
      defective human sperm.
AB  - BACKGROUND: Successful gametogenesis requires the establishment of an appropriate
      epigenetic state in developing germ cells. Nevertheless, an association between
      abnormal spermatogenesis and epigenetic disturbances in germline-specific genes
      remains to be demonstrated. METHODS: In this study, the DNA methylation pattern
      of the promoter CpG island (CGI) of two germline regulator genes--DAZL and DAZ,
      was characterized by bisulphite genomic sequencing in quality-fractioned
      ejaculated sperm populations from normozoospermic (NZ) and
      oligoasthenoteratozoospermic (OAT) men. RESULTS: OAT patients display increased
      methylation defects in the DAZL promoter CGI when compared with NZ controls. Such
      differences are recorded when analyzing sperm fractions enriched either in normal
      or defective germ cells (P< 0.001 in both cases). Significant differences in DNA
      methylation profiles are also observable when comparing the qualitatively
      distinct germ cell fractions inside the NZ and OAT groups (P= 0.003 and P= 0.007,
      respectively). Contrastingly, the unmethylation pattern of the DAZ promoter CGI
      remains correctly established in all experimental groups. CONCLUSIONS: An
      association between disrupted DNA methylation of a key spermatogenesis gene and
      abnormal human sperm is described here for the first time. These results suggest
      that incorrect epigenetic marks in germline genes may be correlated with male
      gametogenic defects.

PMID- 20685758
TI  - Array-CGH analysis in patients with syndromic and non-syndromic XY gonadal
      dysgenesis: evaluation of array CGH as diagnostic tool and search for new
      candidate loci.
AB  - BACKGROUND: XY gonadal dysgenesis (XY-GD) is a heterogeneous disorder
      characterized by failure of testicular development despite a normal male
      karyotype. Non-syndromic and syndromic forms can be delineated. Currently, only a
      minority of cases can be explained by gene mutations. METHODS: The aim of this
      study was to detect microdeletions and duplications by using high-resolution
      Agilent oligonucleotide arrays in a cohort of 87 patients with syndromic or non
      syndromic 46,XY-GD. RESULTS: In 26 patients, we identified gains or losses in
      regions including genes involved in XY-GD (DMRT1, SOX9, DAX1) or in regions,
      which have not been described as polymorphic copy number variants (CNVs).
      CONCLUSIONS: This study shows that array comparative genomic hybridization (CGH)
      analysis is a useful tool for the molecular diagnosis of XY-GD as well as for the
      identification of potential candidate genes involved in male sexual development.

PMID- 20685760
TI  - Muscle fiber size increases following resistance training in multiple sclerosis.
AB  - OBJECTIVE: To test the hypothesis that lower body progressive resistance training
      (PRT) leads to an increase of the muscle fiber cross-sectional area (CSA) and a
      shift in the proportion of fiber types in patients with multiple sclerosis (MS).
      METHODS: The present study was a two-arm, randomized controlled trial (RCT).
      Thirty-eight MS patients (Expanded Disability Status Scale (EDSS) 3-5.5) were
      randomized to a PRT group (Exercise, n = 19) or a control group (Control, n =
      19). The Exercise group performed a biweekly 12-week lower body PRT program [five
      exercises progressing from 15RM (Repetition Maximum) towards 8RM], whereas the
      Control group maintained their usual daily activity level during the trial
      period. Muscle biopsies from vastus lateralis were taken before (pre) and after
      the trial (post). Thigh volume (TV) was estimated from anthropometric
      measurements. Isokinetic muscle strength of the knee extensors (KE) and flexors
      (KF) were evaluated at slow (90( degrees )/s) and fast (180( degrees )/s) angular
      velocities. RESULTS: In the Exercise group the mean CSA of all muscle fibers (7.9
      +/- 15.4% vs. -3.5 +/- 9.0%, p = 0.03) and of type II muscle fibers (14.0 +/-
      19.4% vs. -2.6 +/- 15.5%, p = 0.02) increased in comparison with the Control
      group. No changes occurred in the proportion of fiber types in the Exercise
      group. Neither was there any change in total TV. Isokinetic strength at KE180,
      KF90 and KF180 improved significantly after PRT when compared with the control
      group (10.2-21.3%, p <= 0.02). CONCLUSIONS: We conclude that progressive
      resistance training induces a compensatory increase of muscle fiber size in
      patients with the central nervous system disorder, multiple sclerosis.

PMID- 20685759
TI  - Recovery after spinal cord relapse in multiple sclerosis is predicted by radial
      diffusivity.
AB  - BACKGROUND: The aim of this study was to determine whether the diffusion tensor
      derived radial diffusivity and axial diffusivity, measured in the cortico-spinal
      tract in the cervical cord, predict clinical recovery after a cord relapse in
      patients with multiple sclerosis, and change over time. METHODS: Fourteen
      patients were clinically assessed at the onset of a cervical cord relapse and
      after 1, 3 and 6 months. Patients and 13 age-matched healthy controls underwent
      spinal cord diffusion tensor imaging at each time point. The directional
      diffusivities from diffusion tensor imaging, termed radial diffusivity and axial
      diffusivity, were calculated in regions of interest placed in the lateral
      columns, where the cortico-spinal tract is located, and in the anterior and
      posterior columns. Regression analyses identified predictors of clinical outcome,
      adjusting for age, gender, cord cross-sectional area and baseline clinical score,
      and estimated the differences in the rate of change in diffusion tensor imaging
      measures between groups over time, adjusting for changes in cord cross-sectional
      area. RESULTS: Lower radial diffusivity of the cortico-spinal tract at baseline
      was associated with better clinical outcome. As patients improved clinically
      during the follow-up, they showed greater decrease in radial diffusivity of the
      cortico-spinal tract than controls. CONCLUSIONS: The predictive role of radial
      diffusivity and its dynamic changes over time suggest that this index reflects
      spinal cord pathological processes, including resolution of inflammation and
      remyelination, that contribute to clinical recovery in multiple sclerosis. This
      suggests that radial diffusivity may be useful in trials that promote recovery
      after spinal cord injury and could be applied to other neurological diseases
      affecting the spinal cord.

PMID- 20685761
TI  - Multiple sclerosis-associated retrovirus and progressive disability of multiple
      sclerosis.
AB  - Retrovirus-like particles containing the multiple sclerosis-associated retrovirus
      RNA, significantly found in the cerebrospinal fluid of patients with multiple
      sclerosis, have been preliminarily associated with a short-term poor clinical and
      radiological prognosis of the disease. We asked whether these prognostic
      indications are still measurable after a long-term clinical evaluation (10
      years). Our 10-year blind observational study confirms that the presence of
      multiple sclerosis-associated retrovirus in the cerebrospinal fluid of early
      multiple sclerosis patients is associated with a significantly greater rate of
      relapse-unrelated unremitting disability and secondary progression of the
      disease.

PMID- 20685762
TI  - T2 hypointense rims and ring-enhancing lesions in MS.
AB  - BACKGROUND: Hypointense rims peripherally on T2-weighted MRI (rim lesions) have
      been associated with gadolinium ring-enhancing lesions in multiple sclerosis (MS)
      in pathological studies. However, little is known about their frequency, we
      analyzed clinical significance in a cohort of MS sufferers according to routine
      clinical practice. METHODS: We retrospectively reviewed all available MRI scans
      performed on our MS patients between 2000 and 2009. A total of 580 MRI scans from
      257 patients were analyzed. The presence of rim lesions and ring enhancement was
      assessed and counted blind. Furthermore, the correlation between both patterns,
      and with clinical characteristics, was evaluated. RESULTS: Thirty-five rim
      lesions were identified and 9% (24/257) of the patients showed at least one of
      these lesions. Forty ring-enhancing lesions were counted and 12% (29/245) of the
      patients who had undergone gadolinium MRI presented at least one such lesion.
      Thirteen lesions co-localized both patterns (40% of the rim lesions and 33% of
      the ring-enhancing lesions). Rim lesions and ring-enhancing lesions were observed
      in patients with clinically isolated syndrome (7%, 7%), relapsing-remitting (11%,
      15%) and secondary progressive (13%, 9%) but none with primary progressive MS.
      Presence of ring-enhancing lesions was significantly associated with a shorter
      time to reach EDSS (Expanded Disability Status Scale) 4.0 and 6.0 (hazard ratio
      7.6, 95% confidence interval 2.3-24.6). CONCLUSIONS: Rim lesions and ring
      enhancing lesions are present in close to 10% of patients with MS, and frequently
      both lesions appear independently one to the other. The association of ring
      enhancement with worst prognosis needs to be confirmed in prospective studies.

PMID- 20685763
TI  - Improving the translational hit of experimental treatments in multiple sclerosis.
AB  - BACKGROUND: In other neurological diseases, the failure to translate pre-clinical
      findings to effective clinical treatments has been partially attributed to bias
      introduced by shortcomings in the design of animal experiments. OBJECTIVES: Here
      we evaluate published studies of interventions in animal models of multiple
      sclerosis for methodological design and quality and to identify candidate
      interventions with the best evidence of efficacy. METHODS: A systematic review of
      the literature describing experiments testing the effectiveness of interventions
      in animal models of multiple sclerosis was carried out. Data were extracted for
      reported study quality and design and for neurobehavioural outcome. Weighted mean
      difference meta-analysis was used to provide summary estimates of the efficacy
      for drugs where this was reported in five or more publications. RESULTS: The use
      of a drug in a pre-clinical multiple sclerosis model was reported in 1152
      publications, of which 1117 were experimental autoimmune encephalomyelitis (EAE).
      For 36 interventions analysed in greater detail, neurobehavioural score was
      improved by 39.6% (95% CI 34.9-44.2%, p < 0.001). However, few studies reported
      measures to reduce bias, and those reporting randomization or blinding found
      significantly smaller effect sizes. CONCLUSIONS: EAE has proven to be a valuable
      model in elucidating pathogenesis as well as identifying candidate therapies for
      multiple sclerosis. However, there is an inconsistent application of measures to
      limit bias that could be addressed by adopting methodological best practice in
      study design. Our analysis provides an estimate of sample size required for
      different levels of power in future studies and suggests a number of
      interventions for which there are substantial animal data supporting efficacy.

PMID- 20685764
TI  - The management of multiple sclerosis in children: a European view.
AB  - About 3-5% of all patients with multiple sclerosis experience the onset of their
      disease under the age of 16. A significant proportion of paediatric multiple
      sclerosis patients develop significant cognitive disturbances and persistent
      physical disability. The high relapse rate and the morbidity in the paediatric
      multiple sclerosis population has triggered the use of disease-modifying
      therapies that have been shown to reduce relapse rate, disease progression and
      cognitive decline in adult patients with multiple sclerosis. Hard evidence for
      the right treatment and its appropriate timing is scarce in paediatric multiple
      sclerosis. Nevertheless, expertise in this field has grown thanks to recent open
      label trials and experience generated in specialized centres. In spring 2009, a
      first meeting was held in Rotterdam with clinicians from 11 European countries
      (one from Canada) that are all active in the management of paediatric multiple
      sclerosis. One of the aims was to generate a common view on the management of
      paediatric multiple sclerosis patients. The result of this meeting is presented
      here to help standardize treatment and to support clinicians with less experience
      in this field.

PMID- 20685765
TI  - Challenges in screening for depression in multiple sclerosis.
AB  - BACKGROUND: Screening has frequently been proposed as a strategy for detection of
      depression in multiple sclerosis (MS). In a recent study, we found a minimal
      impact of screening, even when this was coupled with rapidly responsive and
      evidence-based depression care. METHODS: In order to explore the challenges
      involved in screening we analyzed prospective data from the Canadian Impact of MS
      (CIMS) database, which provides annual ratings on a self-report depression rating
      scale, the Center for Epidemiologic Studies Depression Rating Scale (CES-D).
      RESULTS: Approximately 30% of respondents screened positive at each visit. CES-D
      ratings correlated fairly strongly from year to year, Pearson's r ranged from
      0.65 to 0.73. Approximately 10% of those below the CES-D cut-point at each
      assessment exceeded the cut-point when rated 1 year later, but only about half of
      these cases had large (>=10 points) increases in their scores. CONCLUSIONS:
      Screening interventions are generally oriented towards early detection, whereas
      the longitudinal pattern of depressive symptoms in MS appears to be characterized
      more prominently by a persistent burden of depressive symptoms in a substantial
      proportion of the population. Resources invested in screening efforts can
      probably be more effectively deployed in other areas, such as improved long-term
      clinical management.

PMID- 20685766
TI  - Characteristic brain magnetic resonance imaging abnormalities in central nervous
      system aquaporin-4 autoimmunity.
AB  - BACKGROUND: Although neuromyelitis optica has been traditionally regarded as a
      disease without brain involvement, brain abnormalities are not uncommon in
      patients with neuromyelitis optica-related disorders. METHODS: We aimed to
      characterize the brain magnetic resonance imaging (MRI) abnormalities in
      neuromyelitis optica spectrum disorder patients who are seropositive for anti
      aquaporin-4 autoantibody (AQP4 Ab). Of 236 consecutive patients with inflammatory
      demyelinating central nervous system diseases, we retrospectively analyzed MRI
      characteristics of 78 patients who were seropositive for AQP4 Ab. RESULTS: For an
      average observational period of 6.3 years, 62 patients (79%) had brain lesions on
      MRI. Twenty-four patients (31%) had brain MRI abnormalities at the onset of
      disease, and 35 (45%) had symptomatic brain involvement. Characteristic brain MRI
      abnormalities were classified into five categories: (1) lesions involving
      corticospinal tracts (e.g. posterior limb of internal capsule and cerebral
      peduncle (44%); (2) extensive hemispheric lesions likely due to vasogenic edema
      (29%); (3) periependymal lesions surrounding aqueduct and the third and fourth
      ventricles (22%); (4) periependymal lesions surrounding lateral ventricles (40%);
      and (5) medullary lesions, often contiguous with cervical lesions (31%). Fifty
      four patients (69%) showed at least one kind of brain abnormality among the five
      characteristic MRI lesions. Ten patients showed gadolinium-enhancing lesions,
      which were characterized by multiple patchy enhancing patterns with blurred
      margins. CONCLUSIONS: In central nervous system AQP4 autoimmunity, brain MRI
      abnormalities were more common than is generally appreciated and were
      characterized by their unique localization and configuration.

PMID- 20685767
TI  - Serum antibodies to conformational and linear epitopes of myelin oligodendrocyte
      glycoprotein are not elevated in the preclinical phase of multiple sclerosis.
AB  - BACKGROUND: The proposed predictive value of serum anti-myelin antibodies for the
      development of multiple sclerosis after a first clinically isolated syndrome was
      recently challenged. OBJECTIVE: To investigate myelin autoantibodies before first
      disease manifestation using different detection methods. METHODS: Patients with
      multiple sclerosis who had donated blood at a time prior to development of
      clinically isolated syndrome were identified via the German National Multiple
      Sclerosis Society. Control sera were obtained from age- and gender-matched blood
      donors. IgG-/IgM-antibodies against the extracellular part of native, cell
      surface-expressed myelin oligodendrocyte glycoprotein were detected by flow
      cytometry. Antibodies against linear epitopes were identified by immunoblot using
      recombinant myelin oligodendrocyte glycoprotein (aa1-125) and human myelin basic
      protein preparations. RESULTS: Fifty eight serum samples from 25 patients
      covering an interval of 7.3 years-2 months prior to disease onset were available.
      Longitudinal investigations were performed in 19 patients (2-14 samples per
      patient, 7 years-2 months prior to disease onset). No significant differences in
      the prevalence or titres of anti-myelin antibodies were detected between sera of
      preclinical individuals and healthy donors by either flow cytometry or
      immunoblot. There was no correlation between interval before clinically isolated
      syndrome and autoantibody status. Occurrence of antibodies was not associated
      with symptomatology/severity of clinically isolated syndrome. CONCLUSION: Neither
      anti-myelin autoantibodies against cell surface-expressed native myelin
      oligodendrocyte glycoprotein nor against linear epitopes have a predictive or
      discriminative role during the preclinical disease phase for developing
      clinically isolated syndrome or multiple sclerosis later in life.

PMID- 20685768
TI  - HLA-DRB1*1501 intensifies the impact of IL-6 promoter polymorphism on the
      susceptibility to multiple sclerosis in an Iranian population.
AB  - BACKGROUND: The multifunctional cytokine interleukin-6 (IL-6) is involved in
      inflammatory processes in the central nervous system. It is well documented that
      amount of IL-6 is increased in serum, cerebrospinal fluid and central nervous
      system lesions of patients with multiple sclerosis. A single nucleotide
      polymorphism at position -174 in the IL-6 gene promotor appears to influence IL-6
      expression. Recently, several researchers have focused on HLA-DRB alleles,
      specifically HLA-DRB1*1501, as a potential risk allele in the pathogenesis of
      multiple sclerosis. OBJECTIVE: To investigate the possible influence of IL-6/-174
      polymorphisms on susceptibility to multiple sclerosis and its integration with
      HLA-DRB1*1501. Genomic DNA was extracted from whole blood of 345 patients with
      multiple sclerosis and 426 control subjects. METHOD: The SSP-PCR method was used
      to determine genotypes and Fisher's exact test was applied to determine
      differences between groups. HLA-DRB1*1501 was observed more frequently among
      multiple sclerosis patients compared with healthy subjects (45% and 34%,
      respectively; OR = 1.6, 95% CI = 1.2-2.2, p = 0.0018). At the IL-6/-174 position,
      the G allele had higher frequency among multiple sclerosis patients compared with
      controls (77% and 70%, respectively; OR = 1.4, 95% CI = 1.1-1.8, p = 0.0038).
      This difference was more significant among HLA-DRB1*1501-positive patients and
      controls (81% and 67%, respectively; OR = 1.9, 95% CI = 1.5-2.5, p < 0.0001).
      RESULTS: Our results have shown that the G allele at the IL-6/-174 promoter
      polymorphism may be associated with development of multiple sclerosis in this
      population, and may be strengthened by HLA-DRB1*1501. CONCLUSIONS: We suggest
      more studies to confirm these results in other populations.

PMID- 20685769
TI  - A threshold sample-enrichment approach in a clinical trial with heterogeneous
      subpopulations.
AB  - BACKGROUND: Large comparative clinical trials usually target a wide-range of
      patients population in which subgroups exist according to certain patients'
      characteristics. Often, scientific knowledge or existing empirical data support
      the assumption that patients' improvement is larger among certain subgroups than
      others. Such information can be used to design a more cost-effective clinical
      trial. PURPOSE: The goal of the article is to use such information to design a
      more cost-effective clinical trial. METHODS: A two-stage sample-enrichment design
      strategy is proposed that begins with enrollment from certain subgroup of
      patients and allows the trial to be terminated for futility in that subgroup.
      RESULTS: Simulation studies show that the two-stage sample-enrichment strategy is
      cost-effective if indeed the null hypothesis of no treatment improvement is true,
      as also so illustrated with data from a completed trial of calcium to prevent
      preeclampsia. LIMITATIONS: Feasibility of the proposed enrichment design relies
      on the knowledge prior to the start of the trial that certain patients can
      benefit more than others from the treatment. Prolonged accrual and longer-waited
      outcomes may hinder utilization of the proposed design. CONCLUSIONS: The two
      stage sample-enrichment approach borrows strength from treatment heterogeneity
      among target patients in a large-scale comparative clinical trial, and is more
      cost-effective if the treatment arms are indeed of no difference.

PMID- 20685770
TI  - Anxiolytic-like effect induced by the cannabinoid CB1 receptor agonist,
      arachydonilcyclopropylamide (ACPA), in the rat amygdala is mediated through the
      D1 and D2 dopaminergic systems.
AB  - In the present study the influence of the dopaminergic system(s) of the amygdala
      on the anxiolytic-like effect of the cannabinoid CB1 receptor agonist,
      arachydonilcyclopropylamide (ACPA), in male Wistar rats was investigated. An
      elevated plus-maze test of anxiety was used to assess anxiety-like behaviors. The
      results showed that bilateral intra-amygdala injections of ACPA (0.125, 1.25 and
      5 ng/rat) and the mixed dopamine D1/D2 receptor agonist, apomorphine, at
      different doses (0.001, 0.01 and 0.1 ug/rat) increased percentage open arm time
      (%OAT) and percentage open arm entries (%OAE), indicating an anxiolytic-like
      effect for both of the drugs. In contrast, intra-amygdala administration of the
      dopamine D1 receptor antagonist SCH23390 (0.5 and 1 ug/rat) and the dopamine D2
      receptor antagonist, sulpiride (2 and 3 ug/rat) decreased %OAT and %OAE,
      suggesting an anxiogenic-like effect for both of the drugs. Interestingly,
      pretreatment with a sub-effective dose of apomorphine (0.0005 ug/rat) increased,
      while SCH23390 (0.25 ug/rat) and sulpiride (1.5 ug/rat) decreased the anxiolytic
      like effect of ACPA. It can be concluded that the dopaminergic system of the
      amygdala may be involved, at least partly, in the anxiolytic-like effects induced
      by ACPA in the rat amygdala.

PMID- 20685771
TI  - Effect of the tyrosine kinase inhibitors (sunitinib, sorafenib, dasatinib, and
      imatinib) on blood glucose levels in diabetic and nondiabetic patients in general
      clinical practice.
AB  - Tyrosine kinase is a key enzyme activity utilized in many intracellular messaging
      pathways. Understanding the role of particular tyrosine kinases in malignancies
      has allowed for the design of tyrosine kinase inhibitors (TKIs), which can target
      these enzymes and interfere with downstream signaling. TKIs have proven to be
      successful in the treatment of chronic myeloid leukemia, renal cell carcinoma and
      gastrointestinal stromal tumor, and other malignancies. Scattered reports have
      suggested that these agents appear to affect blood glucose (BG). We
      retrospectively studied the BG concentrations in diabetic (17) and nondiabetic
      (61) patients treated with dasatinib (8), imatinib (39), sorafenib (23), and
      sunitinib (30) in our clinical practice. Mean declines of BG were dasatinib (53
      mg/dL), imatinib (9 mg/dL), sorafenib (12 mg/dL), and sunitinib (14 mg/dL). All
      these declines in BG were statistically significant. Of note, 47% (8/17) of the
      patients with diabetes were able to discontinue their medications, including
      insulin in some patients. Only one diabetic patient developed symptomatic
      hypoglycemia while on sunitinib. The mechanism for the hypoglycemic effect of
      these drugs is unclear, but of the four agents tested, c-kit and PDGFRbeta are
      the common target kinases. Clinicians should keep the potential hypoglycemic
      effects of these agents in mind; modification of hypoglycemic agents may be
      required in diabetic patients. These results also suggest that inhibition of a
      tyrosine kinase, be it c-kit, PDGFRbeta or some other undefined target, may
      improve diabetes mellitus BG control and it deserves further study as a potential
      novel therapeutic option.

PMID- 20685772
TI  - Dose-sensitive steroid-induced hyperglycaemia.
AB  - Steroids cause significant but under-appreciated and poorly managed glucose
      intolerance. In this case we describe a patient with steroid-induced
      hyperglycaemia who obtained a large positive impact on glycaemic control from a
      small reduction in her steroid dose, sufficient to alleviate the need for
      insulin. Developments in the treatment of steroid-induced hyperglycaemia may mean
      that a more active approach needs to be considered when treating steroid-related
      diabetes in patients whose management is palliative. We advise checking for
      steroid-induced hyperglycaemia by testing capillary blood glucose values 2 hours
      after the lunchtime meal and recommend a single morning dose of long-acting
      insulin to treat the condition.

PMID- 20685773
TI  - Clinical and immunoserological characteristics of the transition from primary to
      overlap antiphospholipid syndrome.
AB  - Antiphospholipid syndrome (APS) is a distinct clinical entity characterized by
      arterial and venous thromboembolic events, recurrent fetal loss and the presence
      of antiphospholipid antibodies in the patients' sera. In primary APS, there is no
      detectable underlying disease, while overlap APS is associated with clinical
      syndromes including systemic autoimmune diseases, infections, or malignancies. We
      carried out a retrospective analysis of serological and clinical manifestations
      as well as assessed outcome-measures in 165 patients with primary APS. Thrombotic
      manifestations and possible signs of autoimmune diseases were determined at the
      time of the diagnosis, followed by the analysis of recurrent thrombotic events
      and effects of therapy during the follow-up period. Among the 165 patients with
      primary APS at onset, 105 patients (63%) remained primary APS after a mean 5.2
      years of follow-up. In 14% of the patients, subsequently APS became associated
      with various characteristics of undifferentiated connective tissue disease.
      Finally 23% of patients evolved into a definitive systemic autoimmune disease
      during a mean 9.75 years of follow-up. Recurrent thrombotic events were
      registered in 24% of patients. Our results suggest that primary APS may be
      considered as a potential early phase of a dynamic transition towards a well
      defined systemic autoimmune disease.

PMID- 20685774
TI  - Ye olde Tudor health market.

PMID- 20685776
TI  - When is restraint appropriate?

PMID- 20685779
TI  - Recurrent vomiting and lethargy in an infant--just another viral illness?

PMID- 20685783
TI  - Competing interests. More queries about H1N1 scandal.

PMID- 20685784
TI  - GAVI (Global Alliance for Vaccines and Immunisation) and WHO. Demanding
      accountability.

PMID- 20685785
TI  - Medical complicity in torture. Time for WMA to take action.

PMID- 20685786
TI  - Delays in paediatric surgery. "Own goal" or patients' penalty?

PMID- 20685787
TI  - Bronchiectasis. Prevalence in general practice.

PMID- 20685789
TI  - AIDS and elderly people. Elderly Africans have AIDS too.

PMID- 20685790
TI  - Symmetrical polyarthritis. Time for treatment targets in rheumatoid arthritis.

PMID- 20685791
TI  - BMJ on obesity. What the journal says.

PMID- 20685792
TI  - Tax on sugared drinks. How to raise the prices of unhealthy foods.

PMID- 20685794
TI  - Coalition plans for English NHS. A recipe for disaster?

PMID- 20685795
TI  - Coalition plans for English NHS. We need some managers.

PMID- 20685798
TI  - Bulletin campaigns against withdrawal of Mixtard 30.

PMID- 20685799
TI  - Genetic testing services are to be regulated to protect UK patients.

PMID- 20685801
TI  - If it works why can't we have it? Sequential anti-TNF therapy in the UK.

PMID- 20685800
TI  - Characteristics of HIV infected adolescents in Latin America: results from the
      NISDI pediatric study.
AB  - OBJECTIVE: HIV-infected adolescents are a heterogeneous population; source of
      infection, immunodeficiency severity and antiretroviral (ARV) experience vary.
      Here, we describe youth followed in an observational study at Latin American
      sites of the NICHD International Site Development Initiative (NISDI). METHODS:
      The NISDI pediatric protocol is an ongoing prospective cohort study that collects
      demographic, clinical, immunologic, virologic and medication data. Youth were
      enrolled at 15 sites in Brazil, Argentina and Mexico between 2002 and 2006. HIV
      infected subjects aged 12-21 years at the time of enrollment were analyzed.
      RESULTS: Data from 120 HIV-infected youth were analyzed. Sixty-nine (58%) had
      acquired HIV through vertical transmission (VT); 51(42%) via horizontal
      transmission (HT). Twenty-eight percent of the VT group were not diagnosed until
      they were >=10 years of age. Ninety-one percent of the VT group and 46% of the HT
      were receiving ARV at enrollment. Modes of HT included sexual (ST), blood product
      transfusion (BPT) and unknown (U). Severe immunodeficiency was frequent (21%) in
      the ST group. Low BMI was frequent in the VT and BPT sub-groups. Utilization of
      HAART increased over the course of the study, but viral suppression was present
      in only 38% of the VT group and 37% of the HT group at study end. CONCLUSIONS:
      This cohort of HIV-infected adolescents in Latin America displayed a diverse
      epidemiologic pattern. Care providers must be prepared to address the diverse
      needs and challenges of this population. The levels of virologic suppression
      achieved were inadequate. Further research into appropriate interventions for
      this population is urgently needed.

PMID- 20685802
TI  - The impact of rheumatological evaluation in the management of patients with
      interstitial lung disease.
AB  - OBJECTIVE: We hypothesized that multi-disciplinary assessment of patients with
      interstitial lung disease (ILD) would lead to improved diagnosis and management.
      METHODS: Our multi-disciplinary ILD group evaluated 50 patients referred to our
      tertiary care practice over a 12-month period. Evaluation consisted of
      independent assessments by a pulmonologist and rheumatologist, including complete
      history and physical examination, review of laboratory data, as well as review of
      imaging and pathological specimens in conjunction with a radiologist and
      pathologist experienced in ILD. Therapy was initiated or changed in collaboration
      with the referring physicians. RESULTS: Mean age was 65 years for patients with
      rheumatic or CTD-related ILD (CTD-ILD) and 70 years for those with idiopathic
      pulmonary fibrosis (IPF). The final diagnosis after evaluation in the clinic was
      25 patients with CTD-ILD, 15 patients with IPF and 10 patients with other forms
      of lung disease. Of the patients with a final diagnosis of CTD-ILD, 28% were
      referred with a diagnosis of IPF. Among those referred with CTD-ILD, 36% had
      their diagnosis changed to an alternate CTD-ILD. In total, the diagnosis was
      changed in 54% of patients who presented to the ILD clinic. Changes in therapy
      occurred in 80% of patients with CTD-ILD and in 27% of patients with IPF.
      CONCLUSION: A multi-disciplinary ILD clinic offers patients an innovative mode of
      health-care delivery that can enhance diagnosis, affect treatment regimens and
      improve quality of care. Rheumatologists play a significant role in the clinical
      care of these patients and should evaluate all patients with ILD.

PMID- 20685803
TI  - Congenital amusia in speakers of a tone language: association with lexical tone
      agnosia.
AB  - Congenital amusia is a neurogenetic disorder that affects the processing of
      musical pitch in speakers of non-tonal languages like English and French. We
      assessed whether this musical disorder exists among speakers of Mandarin Chinese
      who use pitch to alter the meaning of words. Using the Montreal Battery of
      Evaluation of Amusia, we tested 117 healthy young Mandarin speakers with no self
      declared musical problems and 22 individuals who reported musical difficulties
      and scored two standard deviations below the mean obtained by the Mandarin
      speakers without amusia. These 22 amusic individuals showed a similar pattern of
      musical impairment as did amusic speakers of non-tonal languages, by exhibiting a
      more pronounced deficit in melody than in rhythm processing. Furthermore, nearly
      half the tested amusics had impairments in the discrimination and identification
      of Mandarin lexical tones. Six showed marked impairments, displaying what could
      be called lexical tone agnosia, but had normal tone production. Our results show
      that speakers of tone languages such as Mandarin may experience musical pitch
      disorder despite early exposure to speech-relevant pitch contrasts. The observed
      association between the musical disorder and lexical tone difficulty indicates
      that the pitch disorder as defining congenital amusia is not specific to music or
      culture but is rather general in nature.

PMID- 20685804
TI  - Microseizures and the spatiotemporal scales of human partial epilepsy.
AB  - Focal seizures appear to start abruptly and unpredictably when recorded from
      volumes of brain probed by clinical intracranial electroencephalograms. To
      investigate the spatiotemporal scale of focal epilepsy, wide-bandwidth
      electrophysiological recordings were obtained using clinical macro- and research
      microelectrodes in patients with epilepsy and control subjects with intractable
      facial pain. Seizure-like events not detectable on clinical macroelectrodes were
      observed on isolated microelectrodes. These 'microseizures' were sparsely
      distributed, more frequent in brain regions that generated seizures, and
      sporadically evolved into large-scale clinical seizures. Rare microseizures
      observed in control patients suggest that this phenomenon is ubiquitous, but
      their density distinguishes normal from epileptic brain. Epileptogenesis may
      involve the creation of these topographically fractured microdomains and
      ictogenesis (seizure generation), the dynamics of their interaction and spread.

PMID- 20685805
TI  - Altered awareness of action in schizophrenia: a specific deficit in predicting
      action consequences.
AB  - Patients suffering from schizophrenia may report unusual experiences of their own
      actions. They may either feel that external forces are controlling their actions
      or even their thoughts, or they may feel in control of events that in fact are
      not caused by their actions. Most theories link these disturbances in the sense
      of agency to deficits in motor prediction, resulting in a mismatch between
      predicted and actual sensory feedback at a central comparator mechanism. Such
      theories therefore can account for situations in which the sense of agency is
      reduced. However, other experiments as well as clinical observations show an
      enhanced rather than reduced sense of agency in schizophrenic patients. Here, we
      distinguish between a predictive and a retrospective mechanism where both
      contribute to the experience of agency, and show that schizophrenia is associated
      with a specific impairment to the predictive component. We measured subjective
      time estimates of self-initiated voluntary action (a key press) that were
      followed by a sensory effect (a tone). When the voluntary actions had a high
      probability of causing tones, healthy volunteers showed a predictive shift of the
      perceptual estimate of the action towards the tone, even on occasional trials
      where the tone was omitted. No such shift occurred in the absence of the tone on
      blocks when tones were less frequent. The predictive component of action
      awareness was calculated as the difference between time estimates on 'action
      only' trials from blocks with lower and higher tone probabilities. Schizophrenic
      patients lacked this predictive component of action awareness, showing a shift on
      'action only' trials, regardless of the probability of the tone. Importantly, the
      schizophrenic deficit in predicting the relation between action and effect was
      strongly correlated with severity of positive psychotic symptoms, specifically
      delusions and hallucinations. Furthermore, the patients showed an exaggerated
      retrospective binding between action and tone, shifting the perceived time of
      action whenever the tone occurred, relative to when it did not occur. Our
      quantitative, implicit measures show how basic sensory and motor experience may
      be altered in acute psychosis. The enhanced sense of agency in schizophrenia
      reflects reliance on retrospection, rather than prediction, to associate actions
      with external events. The failure to predict the effects of one's own actions may
      underlie the blurring and confusion in the relationship between the self and the
      world that characterizes acute psychosis.

PMID- 20685806
TI  - Effectiveness of transcranial direct current stimulation and visual illusion on
      neuropathic pain in spinal cord injury.
AB  - The aim of this study was to evaluate the analgesic effect of transcranial direct
      current stimulation of the motor cortex and techniques of visual illusion,
      applied isolated or combined, in patients with neuropathic pain following spinal
      cord injury. In a sham controlled, double-blind, parallel group design, 39
      patients were randomized into four groups receiving transcranial direct current
      stimulation with walking visual illusion or with control illusion and sham
      stimulation with visual illusion or with control illusion. For transcranial
      direct current stimulation, the anode was placed over the primary motor cortex.
      Each patient received ten treatment sessions during two consecutive weeks.
      Clinical assessment was performed before, after the last day of treatment, after
      2 and 4 weeks follow-up and after 12 weeks. Clinical assessment included overall
      pain intensity perception, Neuropathic Pain Symptom Inventory and Brief Pain
      Inventory. The combination of transcranial direct current stimulation and visual
      illusion reduced the intensity of neuropathic pain significantly more than any of
      the single interventions. Patients receiving transcranial direct current
      stimulation and visual illusion experienced a significant improvement in all pain
      subtypes, while patients in the transcranial direct current stimulation group
      showed improvement in continuous and paroxysmal pain, and those in the visual
      illusion group improved only in continuous pain and dysaesthesias. At 12 weeks
      after treatment, the combined treatment group still presented significant
      improvement on the overall pain intensity perception, whereas no improvements
      were reported in the other three groups. Our results demonstrate that
      transcranial direct current stimulation and visual illusion can be effective in
      the management of neuropathic pain following spinal cord injury, with minimal
      side effects and with good tolerability.

PMID- 20685807
TI  - Extensive cardiac lipoma with aneurysmal right ventricle.
AB  - A 56-year-old female with history of mitral valve replacement and automated
      implantable cardioverter-defibrillator placement presented with dyspnea on
      exertion for two years and recurrent ascites. Imaging studies, including
      transthoracic and transesophageal echocardiograms as well as 64-slice computed
      tomography (CT) angiogram revealed a large mass encasing the entire heart
      consistent with lipoma. In addition, a right ventricular free wall aneurysm was
      found. The patient subsequently underwent surgical repair of the tricuspid valve
      and resection of the right ventricular anterior wall aneurysm. The anterior
      portion of the cardiac lipoma was also resected. Gross specimen revealed an
      11.5*6.5*5 cm mass of adipose tissue without malignancy. In this case, the
      patient presented with symptoms of congestive heart failure due to the aneurysm
      in the right ventricle.

PMID- 20685808
TI  - Emergent coronary artery bypass grafting after a broken Rotablator drive-shaft.
AB  - A 75-year-old man, who presented with acute myocardial infarction and cardiogenic
      shock underwent emergency cardiac catheterization, assisted by catecholamine
      administration, respiratory support with intubation and intra-aortic balloon
      pumping (IABP). The coronary arteriogram showed a high-grade obstruction of two
      main branches of the left coronary artery. The occlusion of the left anterior
      descending coronary artery required immediate treatment. As it was heavily
      calcified, the cardiologists were forced to use Rotablator(r), but the device
      became stuck and the drive-shaft broke. An emergency coronary artery bypass
      grafting (CABG) with left internal thoracic artery and saphenous vein graft and
      mitral valve annuloplasty was performed successfully. The patient was weaned off
      IABP on the fourth postoperative day, and a defibrillator was implanted on the
      81st postoperative day because of heart failure. After these procedures, his
      general state improved gradually and he was able to leave the hospital, walking
      alone on the 101st postoperative day. Various reports have appeared describing
      residual foreign bodies in coronary arteries, and almost 90% of these cases can
      be dealt with by intravascular procedures, but some need removal by open-chest
      surgery. An early decision by the cardiologists to go to surgery is recommended
      to save lives. There has been no previous report of emergent CABG after a stuck
      Rotablator(r) tip due to a 'broken drive-shaft'. However, because damage is
      possible even with reliable devices, there should be no hesitation converting to
      open-heart surgery in such cases.

PMID- 20685809
TI  - Use of pericardial strip for reinforcement of proximal anastomosis in Bentall's
      procedure.
AB  - Bleeding from a proximal suture line is not uncommon following composite graft
      anastomosis in Bentall's procedure. Passage of valve sutures through the
      pericardial strip, which is used to encircle the sewing ring of the composite
      graft, strengthens the repair. The strip can also be sutured to the left
      ventricular outflow tract in case of bleeding from proximal anastomosis in that
      particular region.

PMID- 20685810
TI  - Role of reduced expression of SMAD4 in papillary thyroid carcinoma.
AB  - It has been demonstrated that transforming growth factor-beta (TGFbeta) and other
      members of TGFbeta superfamily play an important role in thyroid proliferative
      diseases. The deficiencies of SMAD4 are responsible to accelerate the malignant
      progression of neoplastic lesions in several types of tumors. Therefore, the
      objective of the present study was to determine the functional role of reduced
      expression of SMAD4 in human papillary thyroid carcinogenesis. For this purpose,
      we examined the TGFbeta response in two cell lines, TPC-1 and BCPAP. Our data
      demonstrated for the first time that these cells showed a strong reduction in the
      level of SMAD4 protein, which was responsible for an alteration of TGFbeta
      signaling and for some of the TGFbeta-mediated biological effects. The
      overexpression of SMAD4, restoring TGFbeta transduction, determined a significant
      increase of antiproliferative response to TGFbeta, and reduced the invasive
      behavior of these cells. Therefore, our data indicated that reduction of SMAD4
      may play a significant role in thyroid carcinogenesis.

PMID- 20685811
TI  - Explaining structural change in cardiovascular mortality in Ireland 1995-2005: a
      time series analysis.
AB  - BACKGROUND: Deaths from diseases of the circulatory system and the seasonality of
      deaths from these causes fell sharply between 1995 and 2005 among older age
      groups in Ireland. We examine whether a structural break occurred in deaths from
      circulatory causes in Ireland between 1995 and 2005 and test whether this can be
      statistically accounted for by cardiovascular prescribing during the same period
      controlling for weather trends. METHODS: Grouped logit time series models were
      used to identify if and at which quarter a structural break occurred in Irish
      circulatory deaths between 1995 and 2005. Data on cardiovascular prescribing and
      temperature within the quarter were entered into the trend-break model to account
      for the structural break. RESULTS: Controlling for temperature, beta-blocker, ace
      inhibitor and aspirin medications rendered the structural break indicator
      insignificant among all age groups for men. Diuretic, statin and calcium channel
      blocker medications could not account for the break point for men aged 75-84
      years. beta-Blocker, aspirin and calcium channel blocker medications account for
      mortality trends among all age groups among women. Ace inhibitor and statin could
      not account for trends amongst women aged 65-74 years and nitrates and diuretics
      did not account for trends for any age group. CONCLUSIONS: Cardiovascular
      prescribing accounts for the trend break in circulatory mortality among men and
      women aged >=65 years after 1999 in Ireland but the effect of prescribing is
      lower for women. beta-Blocker, ace inhibitor and aspirin medications were more
      successful than statin, diuretic and nitrates in accounting for the trends.

PMID- 20685812
TI  - Increasing socio-economic inequality in type 2 diabetes prevalence--repeated
      cross-sectional surveys in England 1994-2006.
AB  - BACKGROUND: This study aimed to evaluate the association of rising type 2
      diabetes prevalence with socio-economic inequality in diabetes. METHODS: Data
      from the Health Survey for England were analysed for 1994, 1998, 2003 and 2006.
      This is a nationally representative annual survey of private households. Data for
      41,643 individuals aged >=35 years were included. The prevalence of self-reported
      diabetes diagnosed by a doctor was analysed in relation to household income,
      occupational social class and educational qualifications. Data were standardized
      for age using the European Standard Population for reference. RESULTS: Prevalence
      of diagnosed diabetes increased in men from 3.74% in 1994 to 7.25% in 2006, and
      in women from 2.28% to 4.88%. In 1994, there were no associations between social
      class or educational level and diabetes prevalence evident. In 2006, there was
      evidence of a negative association in women [prevalence ratio for social class
      (IV + V vs. I) = 4.54, P-value for trend = 0.005; prevalence ratio for
      educational level ('none' vs. 'A-levels') = 1.96, P-value for trend = 0.001]. The
      Slope Index of Inequality (SII) for social class in women increased from -1.65 in
      1994 to -4.95 [95% Confidence Interval (95% CI -8.52 to -1.38)] in 2006 and for
      level of education from -1.39 to -6.48 (95% CI -9.03 to -3.93). In men, diabetes
      prevalence was not associated with social class or level of education.
      CONCLUSION: Increasing prevalence of type 2 diabetes has been associated with an
      increase of socio-economic inequality in women. There was no socio-economic
      gradient observed in men.

PMID- 20685813
TI  - The ageing of HIV: implications for geriatric medicine.
AB  - The prevalence of human immunodeficiency virus (HIV) in the over 50 age group is
      increasing as a consequence of younger adults ageing with HIV, in addition to new
      diagnoses in later life. We conducted searches in MEDLINE for English language
      studies published between January 1984 and January 2010 using search terms 'HIV',
      'AIDS', 'HIV testing' and 'HIV complications' and selected articles relevant to
      adults aged 50 years and over. The prevalence, natural history and complications
      of HIV infection and treatment in older adults are reviewed. In 2007 the Centers
      for Disease Control and Prevention in the United States reported that 16.8% of
      new diagnoses of HIV that year were in individuals aged over 50 years. Older
      adults are vulnerable to late or missed diagnosis, and poorer treatment outcomes,
      due to the misconception that they are not at risk. A heightened awareness of HIV
      as a possible diagnosis in older adults is becoming increasingly important. As
      the HIV population ages, the emergence of disease and treatment complications
      such as cardiovascular disease, osteoporosis and dementia are evident. Management
      of older adults with HIV and multiple co-morbidities presents challenges to
      infectious diseases physicians and geriatricians alike. Inclusion of older adults
      in future HIV clinical trials will help design healthcare models to provide for
      this growing population.

PMID- 20685814
TI  - Computational identification of tissue-specific alternative splicing elements in
      mouse genes from RNA-Seq.
AB  - Tissue-specific alternative splicing is a key mechanism for generating tissue
      specific proteomic diversity in eukaryotes. Splicing regulatory elements (SREs)
      in pre-mature messenger RNA play a very important role in regulating alternative
      splicing. In this article, we use mouse RNA-Seq data to determine a positive data
      set where SREs are over-represented and a reliable negative data set where the
      same SREs are most likely under-represented for a specific tissue and then employ
      a powerful discriminative approach to identify SREs. We identified 456 putative
      splicing enhancers or silencers, of which 221 were predicted to be tissue
      specific. Most of our tissue-specific SREs are likely different from constitutive
      SREs, since only 18% of our exonic splicing enhancers (ESEs) are contained in
      constitutive RESCUE-ESEs. A relatively small portion (20%) of our SREs is
      included in tissue-specific SREs in human identified in two recent studies. In
      the analysis of position distribution of SREs, we found that a dozen of SREs were
      biased to a specific region. We also identified two very interesting SREs that
      can function as an enhancer in one tissue but a silencer in another tissue from
      the same intronic region. These findings provide insight into the mechanism of
      tissue-specific alternative splicing and give a set of valuable putative SREs for
      further experimental investigations.

PMID- 20685815
TI  - A method for genome-wide analysis of DNA helical tension by means of psoralen-DNA
      photobinding.
AB  - The helical tension of chromosomal DNA is one of the epigenetic landmarks most
      difficult to examine experimentally. The occurrence of DNA crosslinks mediated by
      psoralen photobinding (PB) stands as the only suitable probe for assessing this
      problem. PB is affected by chromatin structure when is done to saturation; but it
      is mainly determined by DNA helical tension when it is done to very low hit
      conditions. Hence, we developed a method for genome-wide analysis of DNA helical
      tension based on PB. We adjusted in vitro PB conditions that discern DNA helical
      tension and applied them to Saccharomyces cerevisiae cells. We selected the in
      vivo cross-linked DNA sequences and identified them on DNA arrays. The entire
      procedure was robust. Comparison of PB obtained in vivo with that obtained in
      vitro with naked DNA revealed that numerous chromosomal regions had deviated PB
      values. Similar analyses in yeast topoisomerase mutants uncovered further PB
      alterations across specific chromosomal domains. These results suggest that
      distinct chromosome compartments might confine different levels of DNA helical
      tension in yeast. Genome-wide analysis of psoralen-DNA PB can be, therefore, a
      useful approach to uncover a trait of the chromosome architecture not amenable to
      other techniques.

PMID- 20685816
TI  - Using protein design algorithms to understand the molecular basis of disease
      caused by protein-DNA interactions: the Pax6 example.
AB  - Quite often a single or a combination of protein mutations is linked to specific
      diseases. However, distinguishing from sequence information which mutations have
      real effects in the protein's function is not trivial. Protein design tools are
      commonly used to explain mutations that affect protein stability, or protein
      protein interaction, but not for mutations that could affect protein-DNA binding.
      Here, we used the protein design algorithm FoldX to model all known missense
      mutations in the paired box domain of Pax6, a highly conserved transcription
      factor involved in eye development and in several diseases such as aniridia. The
      validity of FoldX to deal with protein-DNA interactions was demonstrated by
      showing that high levels of accuracy can be achieved for mutations affecting
      these interactions. Also we showed that protein-design algorithms can accurately
      reproduce experimental DNA-binding logos. We conclude that 88% of the Pax6
      mutations can be linked to changes in intrinsic stability (77%) and/or to its
      capabilities to bind DNA (30%). Our study emphasizes the importance of structure
      based analysis to understand the molecular basis of diseases and shows that
      protein-DNA interactions can be analyzed to the same level of accuracy as protein
      stability, or protein-protein interactions.

PMID- 20685817
TI  - Sensitive enzymatic quantification of 5-hydroxymethylcytosine in genomic DNA.
AB  - The recent discovery of genomic 5-hydroxymethylcytosine (hmC) and mutations
      affecting the respective Tet hydroxylases in leukemia raises fundamental
      questions about this epigenetic modification. We present a sensitive method for
      fast quantification of genomic hmC based on specific transfer of radiolabeled
      glucose to hmC by a purified glucosyltransferase. We determined hmC levels in
      various adult tissues and differentiating embryonic stem cells and show a
      correlation with differential expression of tet genes.

PMID- 20685818
TI  - A reduction of unilateral ureteral obstruction-induced renal fibrosis by a
      therapy combining valsartan with aliskiren.
AB  - The protective effect of combination therapy with valsartan and aliskiren against
      renal fibrosis remains to be defined. This study was undertaken to examine the
      protective effects of the combination of valsartan and aliskiren against renal
      fibrosis induced by unilateral ureteral obstruction (UUO). Combination therapy
      with valsartan (15 mg.kg(-1).day(-1)) and aliskiren (10 mg.kg(-1).day(-1)),
      valsartan monotherapy (30 mg.kg(-1).day(-1)), and aliskiren monotherapy (20
      mg.kg(-1).day(-1)) all significantly ameliorated the increase in blood urea
      nitrogen and the degree of hydronephrosis determined by the increase in weight
      and length of the obstructed kidney. The dose titration study and blood pressure
      measurement confirmed that the combination therapy provided a greater benefit
      independent of the vasodilatory effect. There were no significant changes in
      serum levels of creatinine, sodium, and potassium in UUO rats and any treatment
      groups. Combination therapy also attenuated UUO-related increases in the scores
      of tubular dilatation, interstitial volume, interstitial collagen deposition,
      alpha-smooth muscle actin, the activation of ERK 1/2, the infiltration of
      monocytes/macrophages, the mRNA expression of snail-1, and transforming growth
      factor-beta1 to a greater extent compared with aliskiren or valsartan used alone.
      The mRNA expression of renin and the (pro)renin receptor significantly increased
      after UUO. Combination therapy and monotherapy of valsartan and aliskiren had a
      comparable enhancing effect on the mRNA expression of renin, whereas all these
      treatments did not affect the expression of the (pro)renin receptor. In
      conclusion, a direct renin inhibitor in conjunction with an angiotensin II
      receptor blocker exerts increased renal protection against renal fibrosis and
      inflammation during obstruction over either agent alone.

PMID- 20685819
TI  - Impaired glomerular and tubular antioxidative defense mechanisms in nephrotic
      syndrome.
AB  - The molecular mechanisms behind acquired nephrotic syndrome (NS) are still
      largely unknown. One possible explanation for the development of proteinuria is
      oxidative damage to the glomerular cells. Our hypothesis was that the oxidative
      defense is weakened in NS, and we focused on measurements of the oxidative
      antioxidative status in the glomerular and tubular parts of the nephron. Gene
      expression was analyzed in renal biopsies from patients with NS. In addition, to
      compare the acute and chronic phases of the disease, we studied puromycin-treated
      rats. In the biopsy material, the expression of enzymes involved in the
      antioxidative defense was higher in the tubulointerstitial compartment than in
      the glomerular cells. Real-time PCR analysis revealed a decreased glomerular
      expression in nephrotic kidneys for the antioxidant enzymes catalase and
      glutathione peroxidase-3, and -4. The tubular gene expression was downregulated
      for catalase, glutathione peroxidase-3, and thioredoxin reductase-1 and -2. The
      altered gene expression was accompanied by increased lipid peroxidation in urine.
      In rats, serum concentrations of ascorbyl-free radicals, measured with electron
      spin resonance, were elevated in the acute phase of the disease, suggesting
      increased oxidative stress in the circulation. In addition, we saw an increase in
      the plasma antioxidant capacity combined with a decreased oxidation of proteins
      in sera from nephrotic rats, but not from humans. In conclusion, there is a
      marked downregulation of several antioxidative enzymes in nephrotic kidneys,
      especially in glomerular structures. Our data suggest that oxidative damage to
      glomerular cells may contribute significantly to the course and prognosis of
      nephrotic syndrome.

PMID- 20685820
TI  - Nicotine worsens the severity of nephropathy in diabetic mice: implications for
      the progression of kidney disease in smokers.
AB  - Epidemiological studies have established the role of cigarette smoking as a risk
      factor in the progression of chronic kidney disease, including diabetic
      nephropathy. We have previously reported that nicotine promotes mesangial cell
      proliferation and hypertrophy via activation of nonneuronal nicotinic
      acetylcholine receptors and that nicotine worsens renal injury in a model of
      acute glomerulonephritis (Jaimes E, Tian RX, Raij L. Am J Physiol Heart Circ
      Physiol 292: H76-H82, 2007; Jaimes EA, Tian RX, Joshi M, Raij L. Am J Nephrol 29:
      319-326, 2009). These studies were designed to test the hypothesis that nicotine
      worsens renal injury in db/db mice, a well-established model of diabetic
      nephropathy, and that reactive oxygen species play an important as mediators of
      these effects. For these studies, nicotine (100 MUg/ml) was administered in the
      drinking water to control and db/db mice for 10 wk. Blood pressure was measured
      by the tail-cuff method, and urine was collected for proteinuria. At death,
      kidneys were collected for histology and molecular biology. The administration of
      nicotine did not result in significant changes in blood pressure or blood glucose
      and resulted in cotinine levels similar to those found in the plasma of smokers.
      In diabetic mice, the administration of nicotine significantly increased urinary
      protein excretion (1-fold), glomerular hypertrophy, and mesangial area (~20%).
      These changes were accompanied by significant increases in NADPH oxidase 4 (~30%)
      and increased nitrotyrosine and Akt expression. In vitro, we determined that
      nicotine has additive effects to high glucose on reactive oxygen species
      generation and Akt phosphorylation in human mesangial cells. These findings
      unveil novel mechanisms that may result in the development of novel strategies in
      the treatment and prevention of diabetic nephropathy in smokers.

PMID- 20685821
TI  - Dact2 is expressed in the developing ureteric bud/collecting duct system of the
      kidney and controls morphogenetic behavior of collecting duct cells.
AB  - The overall pattern of the developing kidney is set in large part by the
      developing ureteric bud/collecting duct system, and dysgenesis of this system
      accounts for a variety of clinically significant renal diseases. Understanding
      how the behavior of cells in the developing ureteric bud/collecting duct is
      controlled is therefore important to understanding the normal and abnormal
      kidney. Dact proteins have recently been identified as cytoplasmic regulators of
      intracellular signaling. Dact1 inhibits Wnt signaling, and Dact2 inhibits
      transforming growth factor (TGF)-beta signaling. Here, we report that Dact2 is
      expressed in developing and adult mouse kidneys, specifically in the ureteric
      bud/collecting duct epithelium, a structure whose morphogenesis is controlled
      partially by TGF-beta. When small interfering RNA is used to knock down Dact2
      expression in collecting duct cells, they show some constitutive phospho-Smad2,
      undetectable in controls, and elevated phospho-Smad2 in response to TGF-beta.
      They also show defective migration and, in a monolayer wound-healing assay, they
      fail to assemble a leading edge "cable" of actomyosin and advance instead as a
      disorganized mass of lamellipodium-bearing cells. This effect is seriously
      exacerbated by exogenous TGF-beta, although control cells tolerate it well. In
      three-dimensional culture, Dact2 knockdown cells form cysts and branching
      tubules, but the outlines of the cysts made by knockdown cells are ragged rather
      than smooth and the branching tubules are decorated with many fine spikes not
      seen in controls. These data suggest Dact2 plays a role in regulating
      morphogenesis by renal collecting duct cells, probably by protecting cells from
      overly strong TGF-beta pathway activation.

PMID- 20685823
TI  - PTH increases FGF23 gene expression and mediates the high-FGF23 levels of
      experimental kidney failure: a bone parathyroid feedback loop.
AB  - Parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) target the
      kidney to cause a phosphaturia. FGF23 also acts on the parathyroid to decrease
      PTH expression, but in chronic kidney disease (CKD) there are high-serum PTH and
      FGF23 levels and resistance of the parathyroid to FGF23. We now report that PTH
      acts on bone to increase FGF23 expression and characterize the signal
      transduction pathway whereby PTH increases FGF23 expression. Remarkably, we show
      that PTH is necessary for the high-FGF23 levels of early kidney failure due to an
      adenine high-phosphorus diet. Parathyroidectomy before the diet totally prevented
      the fivefold increase in FGF23 levels in kidney failure rats. Moreover,
      parathyroidectomy of early kidney failure rats corrected their high-FGF23 levels.
      Therefore, in early kidney failure, the high-FGF23 levels are dependent on the
      high-PTH levels. PTH infusion for 3 days to mice with normal renal function
      increased serum FGF23 and calvaria FGF23 mRNA levels. To demonstrate a direct
      effect of PTH on FGF23, we added PTH to rat osteoblast-like UMR106 cells. PTH
      increased FGF23 mRNA levels (4-fold) and this effect was mimicked by a PKA
      activator, forskolin. PTH also decreased SOST mRNA levels (3-fold). SOST codes
      for sclerostin, a Wnt pathway inhibitor, which is a PTH receptor (PTH1R) target.
      The effect of PTH was prevented by added sclerostin. Therefore, PTH increases
      FGF23 expression which involves the PKA and Wnt pathways. The effect of PTH on
      FGF23 completes a bone-parathyroid endocrine feedback loop. Importantly,
      secondary hyperparathyroidism is essential for the high-FGF23 levels in early
      CKD.

PMID- 20685822
TI  - TRPC6 channels and their binding partners in podocytes: role in glomerular
      filtration and pathophysiology.
AB  - Loss or dysfunction of podocytes is a major cause of glomerular kidney disease.
      Several genetic forms of glomerular disease are caused by mutations in genes that
      encode structural elements of the slit diaphragm or the underlying cytoskeleton
      of podocyte foot processes. The recent discovery that gain-of-function mutations
      in Ca(2+)-permeable canonical transient receptor potential-6 channels (TRPC6)
      underlie a subset of familial forms of focal segmental glomerulosclerosis (FSGS)
      has focused attention on the basic cellular physiology of podocytes. Several
      recent studies have examined the role of Ca(2+) dynamics in normal podocyte
      function and their possible contributions to glomerular disease. This review
      summarizes the properties of TRPC6 and related channels, focusing on their
      permeation and gating properties, the nature of mutations associated with
      familial FSGS, and the role of TRPC channels in podocyte cell biology as well as
      in glomerular pathophysiology. TRPC6 interacts with several proteins in
      podocytes, including essential slit diaphragm proteins and mechanosensitive large
      conductance Ca(2+)-activated K(+) channels. The signaling dynamics controlling
      ion channel function and localization in podocytes appear to be quite complex.

PMID- 20685824
TI  - SNPs of metabolism, not stones.

PMID- 20685825
TI  - Expression of angiotensin II type 1 receptor-interacting molecule in normal human
      kidney and IgA nephropathy.
AB  - The intrarenal renin-angiotensin system plays a crucial role in the regulation of
      renal circulation and sodium reabsorption through the activation of vascular,
      glomerular, and tubular angiotensin II type 1 (AT(1)) receptor signaling. We
      previously cloned a molecule that specifically interacted with the murine AT(1)
      receptor to inhibit AT(1) receptor signaling, which we named ATRAP (for AT(1)
      receptor-associated protein). Since murine ATRAP was shown to be highly expressed
      in the kidney, in the present study we investigated expression and distribution
      of human ATRAP in normal kidney and renal biopsy specimens from patients with IgA
      nephropathy. In the normal human kidney, both ATRAP mRNA and protein were widely
      and abundantly distributed along the renal tubules from Bowman's capsule to the
      medullary collecting ducts. In all renal tubular epithelial cells, the ATRAP
      protein colocalized with the AT(1) receptor. In renal biopsy specimens with IgA
      nephropathy, a significant positive correlation between ATRAP and AT(1) receptor
      gene expression was observed. There was also a positive relationship between
      tubulointerstitial ATRAP expression and the estimated glomerular filtration rate
      in patients with IgA nephropathy. Furthermore, we examined the function of the
      tubular AT(1) receptor using an immortalized cell line of mouse distal convoluted
      tubule cells (mDCT) and found that overexpression of ATRAP by adenoviral gene
      transfer suppressed the angiotensin II-mediated increases in transforming growth
      factor-beta production in mDCT cells. These findings suggest that ATRAP might
      play a role in balancing the renal renin-angiotensin system synergistically with
      the AT(1) receptor by counterregulatory effects in IgA nephropathy and propose an
      antagonistic effect of tubular ATRAP on AT(1) receptor signaling.

PMID- 20685826
TI  - Rapid diagnosis and quantification of acute kidney injury using fluorescent ratio
      metric determination of glomerular filtration rate in the rat.
AB  - The rapid diagnosis and quantification of acute kidney injury (AKI) severity
      remain high clinical priorities. By combining intravital fluorescent ratiometric
      two-photon kidney imaging and the two-compartment pharmacokinetics model, we
      demonstrate that rapid quantification of glomerular filtration rate (GFR) can be
      achieved in physiologic and AKI rat kidney models. Using a bolus infusion of a
      mixture of FITC-inulin and a 500-kDa Texas Red dextran, a full spectrum of GFR
      values, ranging from 0.17 to 1.12 ml.min(-1).100 g(-1), was obtained. The GFR
      values thus determined correlated well with values obtained by the standard 2-h
      inulin infusion clearance method with a Pearson's correlation coefficient of
      0.85. In addition, postischemia deterioration was studied by measuring GFR using
      the two-photon approach during 24 h following a 45-min bilateral ischemia clamp
      model. The GFR was found to decline sharply during the initial 4 h followed by a
      nadir with little sign of rising over the ensuing 24-h period. Moreover, a FITC
      labeled 5-kDa dextran was identified as having nearly identical filtration
      characteristics as FITC-inulin, but had markedly increased fluorescent intensity,
      thus minimizing the quantity needed for individual studies. The technique
      reported allows for very rapid GFR determinations, within 10-15 min, based on
      plasma clearance of a freely filtered fluorescence probe, instead of a prolonged
      one-compartment interstitial space reporter molecule clearance employed by other
      technologies.

PMID- 20685827
TI  - Cigarette smoking and second-hand smoking exposure in adolescents with chronic
      kidney disease: a study from the Midwest Pediatric Nephrology Consortium.
AB  - BACKGROUND: Smoking and second-hand smoking [SHS] cause significant
      cardiovascular mortality and morbidity. In healthy individuals and adults with
      chronic kidney disease [CKD], cigarette smoking is associated with albuminuria,
      increased risk for CKD, increased graft loss and progression of renal
      insufficiency. In children, SHS has been associated with higher blood pressure
      variability, blood pressure load, elevated C-reactive protein and decreased
      cognitive function. Using a survey document and urine cotinine, we sought to
      investigate prevalence of cigarette use and SHS in adolescents with CKD. METHODS:
      A cross-sectional study was conducted in which adolescents aged 13 to 18 years
      with CKD were asked to complete a single anonymous self-administered survey. In
      addition, a single freshly voided urine sample for cotinine measurement was
      obtained from eligible subjects. RESULTS: Of 182 subjects, 60 (34%), 25 (14%) and
      93 (52%) were transplant recipients, were dialysis dependent and had a
      glomerulopathy, respectively. Renal status was lacking in four. Twenty-four per
      cent (24%) had smoked at some point in their lives, and 13% had smoked within the
      last 30 days of taking the survey. Fifty-two per cent (52%) of all respondents
      reported living with an adult who smoked, and 54% reported having friends that
      smoked. Forty-seven per cent (47%) and 44% of those who had never smoked lived
      with an adult and had friends that smoked, respectively. There was a discrepancy
      rate of 7% between self-reported non-smokers and urine cotinine, suggesting
      smoking rates were higher. The highest cotinine/creatinine levels among the non
      smokers were observed in those who lived with a smoker and had friends that
      smoked. CONCLUSION: Among adolescents with CKD, cigarette smoking and SHS
      exposure are prevalent and may be important variables to consider when evaluating
      renal and cardiovascular risk factors and outcomes in children with CKD.

PMID- 20685828
TI  - Hypertension in end-stage renal disease: different measures and their prognostic
      significance.
AB  - Hypertension is a risk factor for cardiovascular morbidity and mortality.
      Hypertension affects the majority of haemodialysis (HD) patients. However, in the
      absence of prospective data, accurate assessment of blood pressure (BP) and the
      level to which BP should be targeted remain still to be defined. A direct
      relationship between volume status and BP as well as between hypervolaemia and
      morbidity and mortality in HD patients indicates that normovolaemia is the key
      therapeutic target. Dry-weight reduction by additional ultrafiltration (even in
      the absence of clinical signs of volume overload) combined with daily dietary
      salt restriction or individually lowered dialysate sodium is recommended. Strict
      volume control allows marked reduction of antihypertensive drug treatment or
      makes it even unnecessary. Long, slow, home HD or frequent, short HD sessions or
      nocturnal HD also result in reduction of BP and left ventricular hypertrophy in
      end-stage renal disease patients. It will be interesting to see which
      recommendations will come from a conference sponsored by the Kidney Disease:
      Improving Global Outcomes on optimal BP treatment target in relation to end-organ
      damage and outcomes in HD patients, on antihypertensive drugs and on non
      pharmacological therapies are to be considered in achieving BP targets in this
      population based on a paucity of prospective data.

PMID- 20685829
TI  - Sleep disorders, depressive symptoms and health-related quality of life--a cross
      sectional comparison between kidney transplant recipients and waitlisted patients
      on maintenance dialysis.
AB  - BACKGROUND: Kidney transplantation is believed to improve health-related quality
      of life (HRQoL) of patients requiring renal replacement therapy (RRT). Recent
      studies suggested that the observed difference in HRQoL between kidney transplant
      recipients (Tx) vs patients treated with dialysis may reflect differences in
      patient characteristics. We tested if Tx patients have better HRQoL compared to
      waitlisted (WL) patients treated with dialysis after extensive adjustment for
      covariables. METHODS: Eight hundred and eighty-eight prevalent Tx patients
      followed at a single outpatient transplant clinic and 187 WL patients treated
      with maintenance dialysis in nine dialysis centres were enrolled in this
      observational cross-sectional study. Data about socio-demographic and clinical
      parameters, self-reported depressive symptoms and the most frequent sleep
      disorders assessed by self-reported questionnaires were collected at enrollment.
      HRQoL was assessed by the Kidney Disease Quality of Life Questionnaire. RESULTS:
      Patient characteristics were similar in the Tx vs WL groups: the proportion of
      males (58 vs 60%), mean +/- SD age (49 +/- 13 vs 49 +/- 12) and proportion of
      diabetics (17 vs 18%), respectively, were all similar. Tx patients had
      significantly better HRQoL scores compared to the WL group both in generic
      (Physical function, General health perceptions, Energy/fatigue, Emotional well
      being) and in kidney disease-specific domains (Symptoms/problems, Effect- and
      Burden of kidney disease and Sleep). In multivariate regression models adjusting
      for clinical and socio-demographic characteristics, sleep disorders and
      depressive symptoms, the modality of RRT (WL vs Tx) remained independently
      associated with three (General health perceptions, Effect- and Burden of kidney
      disease) out of the eight HRQoL dimensions analysed. CONCLUSIONS: Kidney Tx
      recipients have significantly better HRQoL compared to WL dialysis patients in
      some, but not all, dimensions of quality of life after accounting for differences
      in patient characteristics. Utilizing multidimensional disease-specific
      questionnaires will allow better understanding of treatment, disease and patient
      related factors potentially affecting quality of life in patients with chronic
      medical conditions.

PMID- 20685830
TI  - Heavy ion irradiation induces autophagy in irradiated C2C12 myoblasts and their
      bystander cells.
AB  - Autophagy is one of the major processes involved in the degradation of
      intracellular materials. Here, we examined the potential impact of heavy ion
      irradiation on the induction of autophagy in irradiated C2C12 mouse myoblasts and
      their non-targeted bystander cells. In irradiated cells, ultrastructural analysis
      revealed the accumulation of autophagic structures at various stages of autophagy
      (i.e. phagophores, autophagosomes and autolysosomes) within 20 min after
      irradiation. Multivesicular bodies (MVBs) and autolysosomes containing MVBs
      (amphisomes) were also observed. Heavy ion irradiation increased the staining of
      microtubule-associated protein 1 light chain 3 and LysoTracker Red (LTR). Such
      enhanced staining was suppressed by an autophagy inhibitor 3-methyladenine. In
      addition to irradiated cells, bystander cells were also positive with LTR
      staining. Altogether, these results suggest that heavy ion irradiation induces
      autophagy not only in irradiated myoblasts but also in their bystander cells.

PMID- 20685831
TI  - Oscillatory pulses in FitzHugh-Nagumo type systems with cross-diffusion.
AB  - We study FitzHugh-Nagumo type reaction-diffusion systems with linear cross
      diffusion terms. Based on an analytical description using piecewise linear
      approximations of the reaction functions, we completely describe the occurrence
      and properties of wavy pulses, patterns of relevance in several biological
      contexts, in two prototypical systems. The pulse wave profiles arising in this
      treatment contain oscillatory tails similar to those in travelling fronts. We
      find a fundamental, intrinsic feature of pulse dynamics in cross-diffusive
      systems--the appearance of pulses in the bistable regime when two fixed points
      exist.

PMID- 20685832
TI  - Low testosterone levels predict all-cause mortality and cardiovascular events in
      women: a prospective cohort study in German primary care patients.
AB  - OBJECTIVE: Although associations between testosterone and cardiovascular (CV)
      morbidity in women have been proposed, no large prospective study has evaluated
      potential associations between testosterone and mortality in women. The objective
      was to determine whether baseline testosterone levels in women are associated
      with future overall or CV morbidity and mortality. DESIGN: Prospective cohort
      study with a 4.5-year follow-up period. METHODS: From a representative sample of
      German primary care practices, 2914 female patients between 18 and 75 years were
      analyzed for the main outcome measures: CV risk factors, CV diseases, and all
      cause mortality. RESULTS: At baseline, the study population was aged 57.96+/
      14.37 years with a mean body mass index of 26.71+/-5.17 kg/m(2). No predictive
      value of total testosterone for incident CV risk factors or CV diseases was
      observed in logistic regressions. Patients with total testosterone levels in the
      lowest quintile Q1, however, had a higher risk to die of any cause or to develop
      a CV event within the follow-up period compared to patients in the collapsed
      quintiles Q2-Q5 in crude and adjusted Cox regression models (all-cause mortality:
      Q2-Q5 versus Q1: crude hazard ratios (HR) 0.49, 95% confidence interval (CI) 0.33
      0.74; adjusted HR 0.62, 95% CI 0.42-0.939; CV events: Q2-Q5 versus Q1: crude HR
      0.54, 95% CI 0.38-0.77; adjusted HR 0.68, 95% CI 0.48-0.97). Kaplan-Meier curves
      revealed similar data. CONCLUSIONS: Low baseline testosterone in women is
      associated with increased all-cause mortality and incident CV events independent
      of traditional risk factors.

PMID- 20685833
TI  - Pituitary adenomas in childhood, adolescence and young adulthood: presentation,
      management, endocrine and metabolic outcomes.
AB  - OBJECTIVE: To elucidate the long-term outcomes of pituitary adenomas diagnosed in
      childhood and adolescence, knowledge of which remains sparse. DESIGN AND METHODS:
      A retrospective review of patients aged <=21 years at diagnosis of pituitary
      adenoma, attending a neuroendocrine service in Liverpool, UK, between 1984-2009.
      RESULTS: There were 41 patients (33 female), mean age at diagnosis 17.3 years
      (range 11-21) and mean follow-up 9.6 years; 29 patients had prolactinomas (15
      macroprolactinomas), 6 non-functioning pituitary adenomas (NFPAs), 5 Cushing's
      disease (CD) and 1 acromegaly. All prolactinoma patients received dopamine
      agonists (DAs) and three also underwent pituitary surgery. Furthermore, ten
      patients underwent surgery: five with CD, one with acromegaly and four with NFPA.
      Four received radiotherapy after surgery. Another ten patients received hormone
      replacement: nine hydrocortisone, five thyroxine, seven sex steroids and five GH;
      another seven had severe asymptomatic GH deficiency. Three female patients were
      treated for infertility (two successfully). Thirteen patients gained significant
      weight (body mass index (BMI) increase >2 kg/m(2)) since diagnosis and 16 in
      total are now obese (BMI>30 kg/m(2)). Five were treated with orlistat and one
      attended a weight management service. Two received antihypertensive medications,
      two had type 2 diabetes and four were treated for dyslipidaemia. CONCLUSIONS:
      This is one of the largest reviews of patients aged 21 or younger at diagnosis of
      pituitary adenoma followed up by a single service. Two-thirds had prolactinomas,
      all were treated with DAs and three underwent surgery. Increased cardiovascular
      risk factors (obesity and dyslipidaemia) and infertility are important sequelae
      and active identification and treatment are necessary.

PMID- 20685834
TI  - Expression of functional bacterial undecaprenyl pyrophosphate synthase in the
      yeast rer2{Delta} mutant and CHO cells.
AB  - During evolution the average chain length of polyisoprenoid glycosyl carrier
      lipids increased from C55 (prokaryotes) to C75 (yeast) to C95 (mammalian cells).
      In this study, the ability of the E. coli enzyme, undecaprenyl pyrophosphate
      synthase (UPPS), to complement the loss of the yeast cis-isoprenyltransferase in
      the rer2Delta mutant was tested to determine if (55)dolichyl phosphate (Dol-P)
      could functionally substitute in the protein N-glycosylation pathway for (75)Dol
      P, the normal isoprenologue synthesized in S. cerevisiae. First, expression of
      UPPS in the yeast mutant was found to complement the growth and the
      hypoglycosylation of carboxypeptidase Y defects suggesting that the
      (55)polyprenyl-P-P intermediate was converted to (55)Dol-P and that (55)Dol-P
      could effectively substitute for (75)Dol-P in the biosynthesis and function of
      Man-P-Dol, Glc-P-Dol and Glc(3)Man(9)GlcNAc(2)-P-P-Dol (mature DLO) in the
      protein N-glycosylation pathway and glycosylphosphatidylinositol anchor assembly.
      In support of this conclusion, mutant cells expressing UPPS (1) synthesized
      (55)Dol-P based on MS analysis, (2) utilized (55)Dol-P to form Man-P-(55)Dol in
      vitro and in vivo, and (3) synthesized N-linked glycoproteins at virtually normal
      rates as assessed by metabolic labeling with [(3)H]mannose. In addition, an N
      terminal GFP-tagged construct of UPPS was shown to localize to the endoplasmic
      reticulum of Chinese hamster ovary cells. Consistent with the synthesis of
      (55)Dol-P by the transfected cells, microsomes from the transfected cells
      synthesized the [(14)C](55)polyprenyl-P-P intermediate when incubated with
      [(14)C]isopentenyl pyrophosphate and [(3)H]Man-P-(55)Dol when incubated with GDP
      [(3)H]Man. These results indicate that (C55)polyisoprenoid chains, significantly
      shorter than the natural glycosyl carrier lipid, can function in the transbilayer
      movement of DLOs in the endoplasmic reticulum of yeast and mammalian cells, and
      that conserved sequences in the cis-isoprenyltransferases are recognized by, yet
      to be identified, binding partners in the endoplasmic reticulum of mammalian
      cells.

PMID- 20685839
TI  - Hyperreactio luteinalis.

PMID- 20685840
TI  - Self-poisoning suicide deaths in England: could improved medical management
      contribute to suicide prevention?
AB  - BACKGROUND: Suicide by self-poisoning is a major cause of death worldwide. Few
      studies have investigated the medical management of fatal self-poisoning. AIM: To
      describe the characteristics and management of a national sample of individuals
      who died by intentional self-poisoning in hospital and assess the quality of care
      that they received. DESIGN: National population-based descriptive study and
      confidential inquiry. METHODS: Adults (aged >= 16 years) who had died by self
      poisoning in English hospitals in 2005 and received a coroner's verdict of
      suicide or undetermined death at inquest were included. Socio-demographic and
      clinical data were collected through detailed questionnaires sent to clinicians
      at the treating hospitals. A panel of three expert assessors rated each case with
      respect to quality of care and likely contribution to the fatal outcome. RESULTS:
      We obtained information on 121 cases (response rate for questionnaires 77%).
      Expert assessors rated 41/104 cases [39% (95% CI 30-49%)] as having received
      inadequate care; in the majority (38/41-93%) of these, this poor care was felt to
      have potentially contributed to the patient's death. The most common reason for a
      rating of inadequate care was poor airway management (recorded in over half of
      inadequate care cases). In three cases, the receipt of inadequate care was
      associated with the presence of some form of advance directive. CONCLUSION: In as
      many as 39% of in-hospital self-poisoning fatalities, the care received may be in
      some way sub-optimal. The challenge for clinical services is to ensure that
      optimal management strategies are implemented in practice.

PMID- 20685841
TI  - Calf pyomyositis caused by Enterococcus faecalis.

PMID- 20685842
TI  - Barriers to cardiovascular disease risk scoring and primary prevention in Europe.
AB  - The prevalence and burden of cardiovascular disease (CVD) is high, and it remains
      the leading cause of death worldwide. Unfortunately, many individuals who are at
      high risk for CVD are not recognized and/or treated. Therefore, programs are
      available to ensure individuals at risk for CVD are identified through
      appropriate risk classification and offered optimal preventative interventions.
      The use of algorithms to determine a global risk score may help to achieve these
      goals. Such global risk-scoring algorithms takes into account the synergistic
      effects between individual risk factors, placing increases in individual risk
      factors into context relative to the overall disease, allowing for a continuum of
      disease risk to be expressed, and identifying patients most likely to derive
      benefit from an intervention. The predictive value of risk scoring such as using
      the Framingham equation is reasonable, analogous to cervical screening, with area
      under the receiver operated characteristic curve a little over 70%. However,
      limitations do exist, and as they are identified adjustments can be made to the
      global risk-scoring algorithms. Limitations include patient-specific issues, such
      as variations in lifetime risk level, ethnicity or socio-economic strata, and
      algorithm-specific issues, such as discrepancies between different algorithms
      arising from varying risk factors evaluated. The use of currently developed
      algorithms is low in general practice, in part, because of the belief that the
      assessment may oversimplify the risk and/or lead to medication overuse.
      Additional hindrances to the use of risk scoring include government or local
      health policy, patient compliance issues and lack of time. A thorough, easy-to
      use, and standardized tool for risk estimation would allow for improvements in
      the primary prevention of CVD.

PMID- 20685843
TI  - Cellulitis in a post-kidney transplant patient--more than meets the eye.

PMID- 20685844
TI  - Antigen receptor signaling to NF-kappaB via CARMA1, BCL10, and MALT1.
AB  - The signaling pathway controlling antigen receptor-induced regulation of the
      transcription factor NF-kappaB plays a key role in lymphocyte activation and
      development and the generation of lymphomas. Work of the past decade has led to
      dramatic progress in the identification and characterization of new players in
      the pathway. Moreover, novel enzymatic activities relevant for this pathway have
      been discovered, which represent interesting drug targets for immuno-suppression
      or lymphoma treatment. Here, we summarize these findings and give an outlook on
      interesting open issues that need to be addressed in the future.

PMID- 20685845
TI  - Folding and finding RNA secondary structure.
AB  - Optimal exploitation of the expanding database of sequences requires rapid
      finding and folding of RNAs. Methods are reviewed that automate folding and
      discovery of RNAs with algorithms that couple thermodynamics with chemical
      mapping, NMR, and/or sequence comparison. New functional noncoding RNAs in genome
      sequences can be found by combining sequence comparison with the assumption that
      functional noncoding RNAs will have more favorable folding free energies than
      other RNAs. When a new RNA is discovered, experiments and sequence comparison can
      restrict folding space so that secondary structure can be rapidly determined with
      the help of predicted free energies. In turn, secondary structure restricts
      folding in three dimensions, which allows modeling of three-dimensional
      structure. An example from a domain of a retrotransposon is described. Discovery
      of new RNAs and their structures will provide insights into evolution, biology,
      and design of therapeutics. Applications to studies of evolution are also
      reviewed.

PMID- 20685848
TI  - Structure-activity relationships of GPR120 agonists based on a docking
      simulation.
AB  - GPR120 is a G protein-coupled receptor expressed preferentially in the intestinal
      tract and adipose tissue, that has been implicated in mediating free fatty acid
      stimulated glucagon-like peptide-1 (GLP-1) secretion. To develop GPR120-specific
      agonists, a series of compounds (denoted as NCG compounds) derived from a
      peroxisome proliferator-activated receptor gamma agonist were synthesized, and
      their structure-activity relationships as GPR120 agonists were explored. To
      examine the agonistic activities of these newly synthesized NCG compounds, and of
      compounds already shown to have GPR120 agonistic activity (grifolic acid and
      MEDICA16), we conducted docking simulation in a GPR120 homology model that was
      developed on the basis of a photoactivated model derived from the crystal
      structure of bovine rhodopsin. We calculated the hydrogen bonding energies
      between the compounds and the GPR120 model. These energies correlated well with
      the GPR120 agonistic activity of the compounds (R(2) = 0.73). NCG21, the NCG
      compound with the lowest calculated hydrogen bonding energy, showed the most
      potent extracellular signal-regulated kinase (ERK) activation in a cloned GPR120
      system. Furthermore, NCG21 potently activated ERK, intracellular calcium
      responses and GLP-1 secretion in murine enteroendocrine STC-1 cells that express
      GPR120 endogenously. Moreover, administration of NCG21 into the mouse colon
      caused an increase in plasma GLP-1 levels. Taken together, our present study
      showed that a docking simulation using a GPR120 homology model might be useful to
      predict the agonistic activity of compounds.

PMID- 20685849
TI  - Research resource: Tissue-specific transcriptomics and cistromics of nuclear
      receptor signaling: a web research resource.
AB  - Nuclear receptors (NRs) are ligand-regulated transcription factors that recruit
      coregulators and other transcription factors to gene promoters to effect
      regulation of tissue-specific transcriptomes. The prodigious rate at which the NR
      signaling field has generated high content gene expression and, more recently,
      genome-wide location analysis datasets has not been matched by a committed effort
      to archiving this information for routine access by bench and clinical
      scientists. As a first step towards this goal, we searched the MEDLINE database
      for studies, which referenced either expression microarray and/or genome-wide
      location analysis datasets in which a NR or NR ligand was an experimental
      variable. A total of 1122 studies encompassing 325 unique organs, tissues,
      primary cells, and cell lines, 35 NRs, and 91 NR ligands were retrieved and
      annotated. The data were incorporated into a new section of the Nuclear Receptor
      Signaling Atlas Molecule Pages, Transcriptomics and Cistromics, for which we
      designed an intuitive, freely accessible user interface to browse the studies.
      Each study links to an abstract, the MEDLINE record, and, where available, Gene
      Expression Omnibus and ArrayExpress records. The resource will be updated on a
      regular basis to provide a current and comprehensive entrez into the sum of
      transcriptomic and cistromic research in this field.

PMID- 20685850
TI  - The cooperative function of nuclear receptor coactivator 1 (NCOA1) and NCOA3 in
      placental development and embryo survival.
AB  - Nuclear receptor coactivator 1 [NCOA1/steroid receptor coactivator (SRC)-1] and
      NCOA3 (SRC-3/AIB1/ACTR) constitute two thirds of the SRC (steroid receptor
      coactivator) family. Although in vitro experiments have suggested overlapping
      functions between NCOA1 and NCOA3, their in vivo functional relationship is
      poorly understood. In this study, NCOA1 and NCOA3 double knockout mice were
      generated to determine the compensatory roles of NCOA1 and NCOA3 in development.
      NCOA1(-/-) mice survived normally, whereas most NCOA3(-/-) embryos were viable at
      embryonic d 13.5 (E13.5). In contrast, the majority of double-knockout (DKO)
      embryos died by E13.5. NCOA1 and NCOA3 are expressed in the labyrinth, and
      labyrinths of NCOA1(+/-);NCOA3(-/-) and DKO placentas were small compared with
      wild-type and single-knockout labyrinths. DKO labyrinths exhibited low densities
      of maternal blood sinuses and fetal capillaries and displayed fetomaternal blood
      transfusion. At the interface between maternal and fetal circulations, layer I
      sinusoidal trophoblast giant cells showed a reduced density of microvilli. Layer
      III syncytiotrophoblasts appeared to accumulate large lipid droplets and have
      reduced density and deepened invaginations of the intrasyncytial bays. The
      endothelial layer in DKO labyrinth showed abnormal morphologies and had large
      lipid droplets. Furthermore, disruption of NCOA1 and NCOA3 increased labyrinth
      trophoblast proliferation and their progenitor gene expression but decreased
      their differentiation gene expression. NCOA1 and NCOA3 deficiencies also affected
      the expression of several genes for placental morphogenesis including TGFbeta-,
      peroxisome proliferator-activated receptor-beta-, and peroxisome proliferator
      activated receptor-gamma-regulated genes and for glucose transportation including
      GLUT1 and Cx26. These findings demonstrate that NCOA1 and NCOA3 cooperatively
      regulate placental morphogenesis and embryo survival.

PMID- 20685851
TI  - Oxidative stress stimulates apoptosis and activates NF-kappaB in osteoblastic
      cells via a PKCbeta/p66shc signaling cascade: counter regulation by estrogens or
      androgens.
AB  - Aging or acute loss of estrogens or androgens increases the levels of reactive
      oxygen species, activates nuclear factor-kappaB (NF-kappaB), and promotes the
      phosphorylation of p66(shc), a redox enzyme that amplifies mitochondrial reactive
      oxygen species generation and stimulates apoptosis. We report that in mesenchymal
      progenitor and osteoblastic cell models, H(2)O(2) activated a protein kinase C
      (PKC)beta/p66(shc)/NF-kappaB signaling cascade and that p66(shc) was an essential
      mediator of the stimulating effects of H(2)O(2) on the apoptosis of osteoblastic
      cells as well as their ability to activate NF-kappaB. 17beta-Estradiol (E(2)) or
      the nonaromatizable androgen dihydrotestosterone abrogated the effects of
      H(2)O(2) on p66(shc) and NF-kappaB activation by attenuating the phosphorylation
      of the redox-sensitive cytoplasmic kinase PKCbeta. Additionally, both E(2) and
      dihydrotestosterone prevented H(2)O(2)-induced apoptosis by a mechanism that
      involved attenuation of p66(shc) resulting from decreased phosphorylation of
      PKCbeta. Consistent with a kinase-mediated mechanism of sex steroid action, the
      effects of E(2) were reproduced by a polymeric form of estradiol that is not
      capable of stimulating the nuclear-initiated actions of ERalpha. These results
      demonstrate that p66(shc) is an essential mediator of the effects of oxidative
      stress on osteoblastic cell apoptosis, NF-kappaB activation, and cytokine
      production. The ability of either estrogen or androgen to attenuate the effects
      of oxidative stress on osteoblastic cell apoptosis, NF-kappaB activation, and
      cytokine production results from their common property to suppress PKCbeta
      induced p66(shc) phosphorylation via a mechanism that does not require
      stimulation of the nuclear-initiated actions of sex steroids.

PMID- 20685852
TI  - Research resource: genome-wide profiling of methylated promoters in endometriosis
      reveals a subtelomeric location of hypermethylation.
AB  - Several lines of evidence indicate that endometriosis could be partially due to
      selective epigenetic deregulations. Promoter hypermethylation of some key genes,
      such as progesterone receptor and aromatase, has been associated with the
      silencing of these genes and might contribute to the disease. However, it is
      unknown whether global alterations in DNA methylation patterns occur in
      endometriosis and to what extent they are involved in its pathogenesis. We
      conducted a whole-genome scanning of methylation status in more than 25,000
      promoters, using methylated DNA immunoprecipitation with hybridization to
      promoter microarrays. We detailed the methylation profiles for each subtype of
      the disease (superficial endometriosis, endometriomas, and deep infiltrating
      endometriosis) and compared them with the profile obtained for the eutopic
      endometrium. In line with the current theory of the endometrial origin of
      endometriosis, the overall methylation profile was highly similar between the
      endometrium and the lesions. It showed promoter regions consistently
      hypomethylated or hypermethylated (more than 1.5-times, as compared with
      endometrium) and others specific to one given subtype. Albeit there was no
      systematic correlation between promoter methylation and expression of nearby
      genes, 35 genes had both methylation and expressional alterations in the lesions.
      These genes, reported here for the first time, might be of interest in the
      development of endometriosis. In addition, hypermethylated regions were located
      at the ends of the chromosomes, whereas hypomethylated regions were randomly
      distributed all along the chromosomes. We postulated that this original
      observation might participate to the chromosomal stability and protect the
      endometriotic lesion against malignancy.

PMID- 20685853
TI  - Conformation of the mineralocorticoid receptor N-terminal domain: evidence for
      induced and stable structure.
AB  - The mineralocorticoid receptor (MR) binds the steroid hormones aldosterone and
      cortisol and has an important physiological role in the control of salt
      homeostasis. Regions of the protein important for gene regulation have been
      mapped to the amino-terminal domain (NTD) and termed activation function (AF)1a,
      AF1b, and middle domain (MD). In the present study, we used a combination of
      biophysical and biochemical techniques to investigate the folding and function of
      the MR-NTD transactivation functions. We demonstrate that MR-AF1a and MR-MD have
      relatively little stable secondary structure but have the propensity to form
      alpha-helical conformation. Induced folding of the MR-MD enhanced protein-protein
      binding with a number of coregulatory proteins, including the coactivator cAMP
      response element-binding protein-binding protein and the corepressors SMRT and
      RIP140. By contrast, the MR-AF1b domain appeared to have a more stable
      conformation consisting predominantly of beta-secondary structure. Furthermore,
      MR-AF1b specifically interacted with the TATA-binding protein, via an LxxLL-like
      motif, in the absence of induced folding. Together, these data suggest that the
      MR-NTD contains a complex transactivation system made up of distinct structural
      and functional domains. The results are discussed in the context of the induced
      folding paradigm for steroid receptor NTDs.

PMID- 20685854
TI  - Human auditory cortex activity shows additive effects of spectral and spatial
      cues during speech segregation.
AB  - In noisy social gatherings, listeners perceptually integrate sounds originating
      from one person's voice (e.g., fundamental frequency (f(0)) and harmonics) at a
      particular location and segregate these from concurrent sounds of other talkers.
      Though increasing the spectral or the spatial distance between talkers promotes
      speech segregation, synergetic effects of spatial and spectral distances are less
      well understood. We studied how spectral and/or spatial distances between 2
      simultaneously presented steady-state vowels contribute to perception and
      activation in auditory cortex using magnetoencephalography. Participants were
      more accurate in identifying both vowels when they differed in f(0) and location
      than when they differed in a single cue only or when they shared the same f(0)
      and location. The combined effect of f(0) and location differences closely
      matched the sum of single effects. The improvement in concurrent vowel
      identification coincided with an object-related negativity that peaked at about
      140 ms after vowel onset. The combined effect of f(0) and location closely
      matched the sum of the single effects even though vowels with different f(0),
      location, or both generated different time courses of neuromagnetic activity. We
      propose that during auditory scene analysis, acoustic differences among the
      various sources are combined linearly to increase the perceptual distance between
      the co-occurring sound objects.

PMID- 20685855
TI  - Salivary cortisone is a potential biomarker for serum free cortisol.
AB  - CONTEXT: Salivary cortisol measurement is used as a practical surrogate for serum
      free cortisol. However, parotid tissue harbors 11beta-hydroxysteroid
      dehydrogenase (11beta-HSD2) activity converting cortisol to cortisone. OBJECTIVE:
      This study was designed to assess the impact of parotid 11beta-HSD2 activity on
      the measurement of salivary cortisol. PATIENTS, DESIGN, AND OUTCOME MEASURES:
      Study participants with changes in circulating corticosteroid-binding globulin
      (CBG) (+/-oral contraceptive, functionally CBG null) and controls were studied
      during adrenal stimulation by ACTH and postoral and iv hydrocortisone
      administration. Simultaneous serum and saliva samples were collected for the
      measurement of total serum cortisol (SerF) by immunoassay, and unbound cortisol
      and cortisone in serum (FreeF and FreeE) and saliva (SalF and SalE) by liquid
      chromatography-tandem mass spectrometry. RESULTS: ACTH stimulation increased
      SerF, FreeF, SalF, SalE, but not FreeE in all individuals. SerF significantly
      decreased after stopping oral contraceptive administration, but FreeF, SalF and
      SalE remained unchanged. In the hydrocortisone administration study, individual
      FreeF and SalE curves were nearly identical and SalE closely reflected FreeF in
      all participants, irrespective of CBG changes. The highest correlation in all (n
      = 537) matched serum-saliva samples was between SalE and FreeF (r = 0.95, P <
      0.0001), and there was no evidence of 11beta-HSD2 saturation. CONCLUSION:
      Salivary cortisol is a useful surrogate for circulating free cortisol, but its
      concentration is determined both by serum free cortisol and parotid metabolism to
      cortisone. We have shown that salivary cortisone closely reflects free serum
      cortisol after adrenal stimulation and hydrocortisone administration and is
      unaffected by CBG changes. Salivary cortisone has potential as a useful surrogate
      for serum free cortisol in research and clinical assessment, and further research
      in states of chronic glucocorticoid excess is now needed.

PMID- 20685856
TI  - Novel heterozygous nonsense GLI2 mutations in patients with hypopituitarism and
      ectopic posterior pituitary lobe without holoprosencephaly.
AB  - CONTEXT: GLI2 is a transcription factor downstream in Sonic Hedgehog signaling,
      acting early in ventral forebrain and pituitary development. GLI2 mutations were
      reported in patients with holoprosencephaly (HPE) and pituitary abnormalities.
      OBJECTIVE: The aim was to report three novel frameshift/nonsense GLI2 mutations
      and the phenotypic variability in the three families. SETTING: The study was
      conducted at a university hospital. PATIENTS AND METHODS: The GLI2 coding region
      of patients with isolated GH deficiency (IGHD) or combined pituitary hormone
      deficiency was amplified by PCR using intronic primers and sequenced. RESULTS:
      Three novel heterozygous GLI2 mutations were identified: c.2362_2368del
      p.L788fsX794 (family 1), c.2081_2084del p.L694fsX722 (family 2), and c.1138 G>T
      p.E380X (family 3). All predict a truncated protein with loss of the C-terminal
      activator domain. The index case of family 1 had polydactyly, hypoglycemia, and
      seizures, and GH, TSH, prolactin, ACTH, LH, and FSH deficiencies. Her mother and
      seven relatives harboring the same mutation had polydactyly, including two uncles
      with IGHD and one cousin with GH, TSH, LH, and FSH deficiencies. In family 2, a
      boy had cryptorchidism, cleft lip and palate, and GH deficiency. In family 3, a
      girl had hypoglycemia, seizures, excessive thirst and polyuria, and GH, ACTH,
      TSH, and antidiuretic hormone deficiencies. Magnetic resonance imaging of four
      patients with GLI2 mutations and hypopituitarism showed a hypoplastic anterior
      pituitary and an ectopic posterior pituitary lobe without HPE. CONCLUSION: We
      describe three novel heterozygous frameshift or nonsense GLI2 mutations,
      predicting truncated proteins lacking the activator domain, associated with IGHD
      or combined pituitary hormone deficiency and ectopic posterior pituitary lobe
      without HPE. These phenotypes support partial penetrance, variable polydactyly,
      midline facial defects, and pituitary hormone deficiencies, including diabetes
      insipidus, conferred by heterozygous frameshift or nonsense GLI2 mutations.

PMID- 20685857
TI  - Clinical characteristics and therapeutic responses in patients with germ-line AIP
      mutations and pituitary adenomas: an international collaborative study.
AB  - CONTEXT: AIP mutations (AIPmut) give rise to a pituitary adenoma predisposition
      that occurs in familial isolated pituitary adenomas and less often in sporadic
      cases. The clinical and therapeutic features of AIPmut-associated pituitary
      adenomas have not been studied comprehensively. OBJECTIVE: The objective of the
      study was to assess clinical/therapeutic characteristics of AIPmut pituitary
      adenomas. DESIGN: This study was an international, multicenter, retrospective
      case collection/database analysis. SETTING: The study was conducted at 36
      tertiary referral endocrine and clinical genetics departments. PATIENTS: Patients
      included 96 patients with germline AIPmut and pituitary adenomas and 232 matched
      AIPmut-negative acromegaly controls. RESULTS: The AIPmut population was
      predominantly young and male (63.5%); first symptoms occurred as
      children/adolescents in 50%. At diagnosis, most tumors were macroadenomas
      (93.3%); extension and invasion was common. Somatotropinomas comprised 78.1% of
      the cohort; there were also prolactinomas (n = 13), nonsecreting adenomas (n =
      7), and a TSH-secreting adenoma. AIPmut somatotropinomas were larger (P =
      0.00026), with higher GH levels (P = 0.00068), more frequent extension (P =
      0.018) and prolactin cosecretion (P = 0.00023), and occurred 2 decades before
      controls (P < 0.000001). Gigantism was more common in the AIPmut group (P <
      0.000001). AIPmut somatotropinoma patients underwent more surgical interventions
      (P = 0.00069) and had lower decreases in GH (P = 0.00037) and IGF-I (P = 0.028)
      and less tumor shrinkage with somatostatin analogs (P < 0.00001) vs. controls.
      AIPmut prolactinomas occurred generally in young males and frequently required
      surgery or radiotherapy. CONCLUSIONS: AIPmut pituitary adenomas have clinical
      features that may negatively impact treatment efficacy. Predisposition for
      aggressive disease in young patients, often in a familial setting, suggests that
      earlier diagnosis of AIPmut pituitary adenomas may have clinical utility.

PMID- 20685858
TI  - Changes in GAD65Ab-specific antiidiotypic antibody levels correlate with changes
      in C-peptide levels and progression to islet cell autoimmunity.
AB  - CONTEXT: The previously reported absence of 65-kDa glutamate decarboxylase
      antibody (GAD65Ab)-specific antiidiotypic antibodies (anti-Id) in type 1 diabetes
      (T1D) patients at clinical onset could be due to an inability to mount an
      antibody response to GAD65Ab or a longitudinal decline in anti-Id levels.
      OBJECTIVE AND DESIGN: We investigated anti-Id levels in longitudinal samples
      obtained from T1D patients (n = 41) (clinical diagnosis - 12 months), and latent
      autoimmune diabetes in adults (LADA) patients (n = 32) who received alum
      formulated human recombinant GAD65 (baseline - 12 months). We also determined
      anti-Id levels in a small cohort of Type 2 diabetes patients during their
      development of autoimmune T cell responses. RESULTS: At clinical onset T1D
      patients presented no or low anti-Id levels. However, 22/41 T1D patients showed
      >=50% increase in GAD65Ab-specific anti-Id levels during follow-up; peaking at 3
      (n = 1), 6 (n = 10), 9 (n = 10), or 12 (n = 1) months. Increasing anti-Id levels
      marked patients who experienced a temporary increase in C-peptide levels. Anti-Id
      levels correlated significantly with glycated hemoglobin and C-peptide levels at
      6 and 9 months (P values ranged from <0.001 to <0.05). In LADA patients receiving
      placebo, anti-Id levels declined in seven of nine patients, whereas four of five
      patients receiving 20 MUg alum-formulated human recombinant GAD65 showed
      increasing anti-Id levels. Changes in anti-Id and C-peptide levels closely
      correlated (P < 0.0001). The significant decline in anti-Id levels (P = 0.03) in
      T2D patients developing T cell autoimmune responses supports our hypothesis that
      declining anti-Id levels are associated with developing islet autoimmunity.
      CONCLUSIONS: The close association between GAD65Ab-specific anti-Id levels and
      beta-cell function may provide a novel marker for the progression of autoimmune
      diabetes.

PMID- 20685859
TI  - Plasma level of pigment epithelium-derived factor is independently associated
      with the development of the metabolic syndrome in Chinese men: a 10-year
      prospective study.
AB  - OBJECTIVE: Pigment epithelium-derived factor (PEDF), a serine protease inhibitor,
      is secreted from the adipose tissue and circulates at high concentrations. A
      recent study found that PEDF played a causal role in obesity-induced insulin
      resistance and metabolic dysfunctions in mice. Here we investigated whether
      circulating PEDF levels predicted the development of the metabolic syndrome
      (MetS) in a 10-yr prospective study. RESEARCH DESIGN AND METHODS: Baseline plasma
      PEDF levels were measured with an ELISA in 520 nondiabetic subjects, recruited
      from the Hong Kong Cardiovascular Risk Factor Prevalence Study cohort. Multiple
      logistic regression was used to analyze whether PEDF was an independent factor
      related to the MetS at baseline. The role of PEDF in predicting the development
      of the MetS over 10 yr was analyzed using Cox regression analysis. RESULTS:
      Plasma levels of PEDF were significantly higher in men than women. At baseline,
      sex-adjusted PEDF levels were significantly higher in subjects with MetS (P <
      0.001), and the association remained significant (odds ratio: 1.17, P = 0.015),
      even after adjustment for covariates. Among the components of the MetS, PEDF was
      independently associated with hypertriglyceridemia (P = 0.026) and hypertension
      (P = 0.005). Of the 396 subjects without the MetS at baseline, a total of 80 had
      developed the MetS over 10 yr. High baseline sex-adjusted PEDF was an independent
      predictor of the development of the MetS in men (hazard ratio: 1.25, P = 0.034)
      but not in women. CONCLUSION: Plasma PEDF was significantly associated with the
      presence of the MetS and predicted the development of the MetS in Chinese men.

PMID- 20685861
TI  - Progesterone increases manganese superoxide dismutase expression via a cAMP
      dependent signaling mediated by noncanonical Wnt5a pathway in human endometrial
      stromal cells.
AB  - CONTEXT: Manganese superoxide dismutase (Mn-SOD), an antioxidant enzyme in the
      mitochondria, protects cells by scavenging superoxide radicals in human
      endometrial stromal cells (ESCs). Mn-SOD increases in ESCs during decidualization
      induced by progesterone. OBJECTIVE: The present study investigated the molecular
      mechanism for Mn-SOD expression induced by progesterone in human ESCs. METHODS:
      ESCs were incubated with medroxyprogesterone acetate (MPA; 10(-6) m) or dibutyryl
      cAMP (0.5 mm) for 17 d. To determine whether a cAMP-dependent signaling pathway
      is involved in the MPA-induced Mn-SOD expression, ESCs were treated with H89, an
      inhibitor of cAMP-dependent protein kinase A. A chromatin immunoprecipitation
      assay was performed to examine the binding of cAMP-binding protein to the cAMP
      response element on the Mn-SOD gene promoter. To examine the involvement of Wnt5a
      signaling, anti-Wnt5a antibodies were used to neutralize the Wnt5a activities.
      RESULTS: Mn-SOD and Wnt5a mRNA levels and intracellular cAMP concentrations were
      significantly increased by MPA. These increases were accompanied by an increase
      in the mRNA expression of IGF-binding protein-1, a marker of decidualization. The
      increase in Mn-SOD mRNA levels by MPA or dibutyryl-cAMP was completely inhibited
      by H89. The chromatin immunoprecipitation assay revealed that MPA induced cAMP
      binding protein binding with cAMP-response element on the Mn-SOD gene promoter.
      The increase in intracellular cAMP concentrations by MPA was completely inhibited
      by treatment with anti-Wnt5a antibodies. MPA treatment had no effects on beta
      catenin expression. CONCLUSIONS: Progesterone increased Mn-SOD expression via a
      cAMP-dependent pathway in ESCs during decidualization. cAMP-dependent signaling
      stimulated by progesterone is mediated by noncanonical Wnt5a pathways that signal
      independently of beta-catenin.

PMID- 20685860
TI  - Severe obesity is associated with symptomatic presentation, higher parathyroid
      hormone levels, and increased gland weight in primary hyperparathyroidism.
AB  - CONTEXT: A relationship between primary hyperparathyroidism (PHPT) and obesity
      has been observed but is incompletely understood. Furthermore, obesity has been
      associated with vitamin D deficiency, suggesting that the three conditions may be
      linked. OBJECTIVE: We hypothesized that PHPT in morbidly obese patients is more
      severe and that the difference may be explained by vitamin D deficiency. DESIGN
      AND SETTING, PARTICIPANTS, AND OUTCOME MEASURES: Records of 196 patients with
      surgically treated PHPT and known body mass index (BMI) were examined. Patients
      were stratified into three BMI groups: group I (nonobese), BMI < 25 kg/m(2) (n =
      54); group II (non-severely obese), BMI 25-34 kg/m(2) (n = 102); and group III
      (severely obese), BMI 35 kg/m(2) or greater (n = 40). RESULTS: Preoperative PTH
      levels were higher in group IotaIotaIota compared with group Iota (181 +/- 153
      vs. 140 +/- 80 pg/ml, p = 0.04). Group III patients had larger tumors on average
      compared with group I (1.8 +/- 1.5 vs. 1.04 +/- 1.5 g, P = 0.0002). In group III,
      BMI positively correlated with parathyroid tumor weight (r = 0.5, P = 0.002).
      Postoperative PTH was higher in group III compared with group Iota (61 +/- 41 vs.
      44 +/- 28 pg/ml, P = 0.02). There was higher frequency of depression,
      musculoskeletal symptoms, weakness, and gastroesophageal reflux disease in group
      III patients. CONCLUSIONS: BMI positively correlated with parathyroid tumor
      weight independent of vitamin D. Severely obese patients have larger parathyroid
      tumor weight, higher pre- and postoperative PTH, and greater symptoms.

PMID- 20685862
TI  - The 25(OH)D/PTH threshold in black women.
AB  - CONTEXT: Black women have lower 25-hydroxyvitamin D [25(OH)D] and higher PTH than
      white women. Recent evidence implicates PTH in adverse cardiovascular outcomes.
      OBJECTIVE: The objective of the study was to determine whether PTH increases at
      lower 25(OH)D levels (the threshold) in black compared with white women. DESIGN:
      Healthy black and white women, aged 20-80 yr were recruited to participate in a
      cross-sectional study of body-composition in black and white women. Measurement
      of serum 25(OH)D and PTH were carried out. SETTING: The study was a convenience
      sample recruited from a community setting. PATIENTS: Healthy black and white
      women were recruited by advertising and a direct mail campaign in a comparative
      study of body composition. Age ranged from 20-to 80 yr. There were 148 black and
      129 white premenopausal participants and 87 black and 139 white postmenopausal
      participants. MAIN OUTCOME: The main outcome was to determine whether the
      threshold for 25(OH)D/PTH differs in black and white women. RESULTS: A threshold
      of 37 nmol/liter (95% confidence interval 35-40) was found for black and 59
      nmol/liter (95% confidence interval 56-63) for white women. These two values were
      significantly different (P < 0.001). CONCLUSIONS: Black women have an increase in
      serum PTH at a lower 25(OH)D level than white women. Negative health outcomes of
      higher PTH should be investigated in black women.

PMID- 20685863
TI  - Circulating levels of soluble klotho and FGF23 in X-linked hypophosphatemia:
      circadian variance, effects of treatment, and relationship to parathyroid status.
AB  - CONTEXT: Circulating fibroblast growth factor (FGF)-23 is variably elevated in
      individuals with X-linked hypophosphatemia (XLH), and klotho has recently been
      shown to effect renal phosphate handling, yet limited data are available on
      circulating FGF23 and klotho in XLH. OBJECTIVE: The objective of the study was to
      characterize circulating FGF23 and klotho in XLH. DESIGN: Children and adults
      with XLH withheld medication for 14 d. Fasting serum FGF23, PTH, klotho,
      phosphate, and 1,25 dihydroxyvitamin D were obtained. Treated adults were also
      sampled, and circadian sampling was performed in selected individuals. SETTING:
      The study was conducted at a hospital research unit at an academic medical
      center. PATIENTS AND OTHER PARTICIPANTS: Participants included 23 individuals
      with XLH and eight controls. INTERVENTIONS: There were no interventions. MAIN
      OUTCOME MEASURES: Serum klotho and FGF23 were measured. RESULTS: FGF23 was
      greater in XLH than in controls and greater in treated XLH subjects compared with
      XLH subjects not receiving medical therapy. Children had higher klotho levels
      than adults, but values in XLH were similar to controls. A strong positive
      correlation between FGF23 and PTH was found in XLH subjects, whereas there was no
      relationship between these variables in controls. Circulating klotho, but not
      FGF23, has a diurnal pattern. CONCLUSIONS: Serum klotho declines with age and
      demonstrates circadian variation but is normal in XLH. Serum FGF23 is similar in
      children and adults, is elevated in XLH, further increases with therapy, and
      demonstrates no diurnal variation. The direct relationship between FGF23 and PTH
      in subjects with XLH suggests that FGF23 regulation of PTH secretion is aberrant
      in this disorder.

PMID- 20685864
TI  - Adiponectin gene polymorphisms are associated with long-chain omega3
      polyunsaturated fatty acids in serum phospholipids in nondiabetic Koreans.
AB  - CONTEXT: Hypoadiponectinemia is caused by interactions between genetic and
      environmental factors, including the quality of dietary fats. OBJECTIVE: We
      investigated the association of single-nucleotide polymorphisms (SNPs) in the
      adiponectin gene (ADIPOQ) with dietary fat intake or fatty acid (FA) composition
      in serum phospholipids, plasma adiponectin, and insulin resistance. METHODS:
      Nondiabetic subjects (n = 1194) were genotyped for three ADIPOQ SNPs (-11377C>G;
      45T>G; 276G>T) after screening of eight sites. Dietary fat intake, FA composition
      in serum phospholipids, adiponectin, and homeostasis model assessment of insulin
      resistance (HOMA-IR) were also measured. RESULTS: The 276G carriers (n = 1082)
      showed lower high-density lipoprotein cholesterol (P = 0.024) and adiponectin (P
      < 0.001) but higher glucose (P = 0.015) and HOMA-IR (P = 0.005) than 276T/T
      subjects (n = 112). No associations were found in other SNPs. After adjusted for
      age, sex, body mass index, and the proportion of 18:2omega6 and 18:3omega3
      (biomarkers of long term essential FA intake), the 276G carriers showed lower
      proportions of total omega3FA (P = 0.026), 20:5omega3 (P = 0.021), and 22:5omega3
      (P = 0.024) in serum phospholipids. Among FAs in serum phospholipids, 18:2omega6
      highly correlated with omega3-polyunsaturated FA (PUFA) intake (r = 0.260, P <
      0.001) and adiponectin (r = 0.150, P < 0.001). The 276G carriers with a higher
      proportion of 18:2omega6 (>=12.5%) exhibited more pronounced characteristics,
      i.e. lower adiponectin (P < 0.001), lower high-density lipoprotein cholesterol (P
      = 0.004), higher HOMA-IR (P = 0.013), and lower long-chain omega3PUFAs
      (20:5omega3, 22:5omega3, and 22:6omega3, P < 0.001). Additionally, the effect of
      276G>T on the relationship between adiponectin and HOMA-IR was modified by
      18:2omega6 proportion. CONCLUSION: ADIPOQ 276G is associated with reduced
      proportion of long-chain omega3PUFAs in serum phospholipids in nondiabetic
      Koreans.

PMID- 20685865
TI  - Use of depot medroxyprogesterone acetate and fracture risk.
AB  - CONTEXT: Depot medroxyprogesterone acetate (DMPA), which has a high rate of use
      among teenagers in Europe and the United States, has been associated with
      impaired bone mineral acquisition during adolescence and accelerated bone loss in
      later life. Studies on the association between DMPA use and fracture risk are
      limited. OBJECTIVE: We aimed at evaluating the relationship between use of
      hormonal contraceptives, specifically DMPA, and fracture risk. DESIGN: We
      conducted a case-control analysis using the United Kingdom-based General Practice
      Research Database. SETTING AND PARTICIPANTS: Participants were females aged 20-44
      yr with an incident fracture diagnosis between 1995 and 2008. MAIN OUTCOME
      MEASURES: Odds ratios (OR) with 95% confidence intervals (CI) of incident
      fracture in relation to exposure to DMPA or combined oral contraceptives were
      assessed. Adjustments were made for smoking, body mass index, and additional
      potential confounders. RESULTS: We identified 17,527 incident fracture cases and
      70,130 control patients (DMPA exposure: 11 and 8%, respectively). Compared with
      nonuse, current use of one to two, three to nine, or 10 or more DMPA
      prescriptions yielded adjusted OR for fractures of 1.18 (95% CI = 0.93-1.49),
      1.36 (95% CI = 1.15-1.60), and 1.54 (95% CI = 1.33-1.78), respectively. Fracture
      risk was highest after longer treatment duration (>2-3 yr), and there was no
      difference in patients below and above the age of 30 yr. For users of combined
      estrogen-containing oral contraceptives, the OR were around 1. CONCLUSIONS: This
      population-based study suggests that use of DMPA is associated with a slightly
      increased risk of fractures.

PMID- 20685866
TI  - Cholesterol biosynthesis pathway intermediates and inhibitors regulate glucose
      stimulated insulin secretion and secretory granule formation in pancreatic beta
      cells.
AB  - Cholesterol is reportedly abundant in the endocrine secretory granule (SG)
      membrane. In this study, we examined the involvement of cholesterol biosynthesis
      intermediates and inhibitors in insulin secretion and SG formation mechanisms.
      There are two routes for the supply of cholesterol to the cells: one via de novo
      biosynthesis and the other via low-density lipoprotein receptor-mediated
      endocytosis. We found that insulin secretion and content are diminished by beta
      hydroxy-beta-methylglutaryl-coenzyme A inhibitor lovastatin but not by
      lipoprotein depletion from the culture medium in MIN6 beta-cells. Cholesterol
      biosynthesis intermediates mevalonate, squalene, and geranylgeranyl pyrophosphate
      enhanced glucose-stimulated insulin secretion, and the former two increased
      insulin content. The glucose-stimulated insulin secretion-enhancing effect of
      geranylgeranyl pyrophosphate was also confirmed in perifusion with rat islets.
      Morphologically, mevalonate and squalene increased the population of SGs without
      affecting their size. In contrast, lovastatin increased the SG size with
      reduction of insulin-accumulating dense cores, leading to a decrease in insulin
      content. Furthermore, insulin was secreted in a constitutive manner, indicating
      disruption of regulated insulin secretion. Because secretogranin III, a
      cholesterol-binding SG-residential granin-family protein, coincides with SG
      localization based on the cholesterol composition, secretogranin III may be
      associated with insulin-accumulating mechanisms. Although the SG membrane
      exhibits a high cholesterol composition, we could not find detergent-resistant
      membrane regions using a lipid raft-residential protein flotillin and a
      fluorescent cholesterol-Si-pyrene probe as markers on a sucrose-density gradient
      fractionation. We suggest that the high cholesterol composition of SG membrane
      with 40-50 mol% is crucial for insulin secretion and SG formation functions.

PMID- 20685867
TI  - Contribution of a membrane estrogen receptor to the estrogenic regulation of body
      temperature and energy homeostasis.
AB  - The hypothalamus is a key region of the central nervous system involved in the
      control of homeostasis, including energy and core body temperature (Tc). 17beta
      Estradiol (E2) regulates Tc, in part, via actions in the basal hypothalamus and
      preoptic area. E2 primarily controls hypothalamic functions via the nuclear
      steroid receptors, estrogen receptor alpha/beta. However, we have previously
      described an E2-responsive, Gq-coupled membrane receptor that reduces the
      postsynaptic inhibitory gamma-aminobutyric acid-ergic tone and attenuates
      postovariectomy body weight gain in female guinea pigs through the administration
      of a selective Gq-mER ligand, STX. To determine the role of Gq-mER in regulating
      Tc, energy and bone homeostasis, ovariectomized female guinea pigs, implanted ip
      with temperature probes, were treated with STX or E2 for 7-8 wk. Tc was recorded
      for 4 wk, whereas food intake and body weight were monitored daily. Bone density
      and fat accumulation were determined postmortem. Both E2 and STX significantly
      reduced Tc in the females compared with controls. STX, similar to E2, reduced
      food intake and fat accumulation and increased tibial bone density. Therefore, a
      Gq-mER-coupled signaling pathway appears to be involved in maintaining
      homeostatic functions and may constitute a novel therapeutic target for treatment
      of hypoestrogenic symptoms.

PMID- 20685868
TI  - Kisspeptin directly regulates neuropeptide Y synthesis and secretion via the
      ERK1/2 and p38 mitogen-activated protein kinase signaling pathways in NPY
      secreting hypothalamic neurons.
AB  - Kisspeptin is a key component of reproduction that directly stimulates GnRH
      neurons. However, recent studies indicate that kisspeptin can indirectly
      stimulate GnRH neurons through unidentified afferent networks. Neuropeptide Y
      (NPY) is another key reproductive hormone that is an afferent stimulator of GnRH
      neurons. Herein, we report kisspeptin receptor Kiss1r mRNA expression in native
      NPY neurons FAC-sorted from NPY-GFP transgenic mice. Thus, we hypothesized that
      kisspeptin indirectly stimulates GnRH neurons through direct regulation of NPY
      neurons. Using hypothalamic NPY-secreting cell lines, we determined that
      kisspeptin stimulates NPY mRNA expression and secretion in the mHypoE-38 cells,
      but not the mHypoE-42 cells, using quantitative RT-PCR and enzyme immunoassays.
      Furthermore, agouti-related peptide, ghrelin, neurotensin, or Kiss1r mRNA
      expression was not changed upon exposure to kisspeptin in either cell line. These
      results concur with our previous work identifying the mHypoE-38 cell line as a
      putative reproductive NPY neuron and the mHypoE-42 cell line as a potential
      feeding-related NPY neuron. In the mHypoE-38 cells, kisspeptin activated the
      ERK1/2 and p38 MAPK kinases as shown by Western blot analysis. Moreover,
      inhibiting the ERK1/2 and p38 pathways with U0126 and SB239063, respectively,
      prevented kisspeptin induction of NPY mRNA expression and secretion. Altogether,
      we find that kisspeptin directly regulates NPY synthesis and secretion via the
      ERK1/2 and p38 MAPK pathways in a NPY-secreting cell line, and we propose NPY
      neurons as an afferent network by which kisspeptin indirectly stimulates GnRH
      secretion.

PMID- 20685870
TI  - Sodium depletion increases sympathetic neurite outgrowth and expression of a
      novel TMEM35 gene-derived protein (TUF1) in the rat adrenal zona glomerulosa.
AB  - The adrenal zona glomerulosa (ZG) secretes aldosterone to regulate sodium
      balance. Chronic sodium restriction increases aldosterone accompanied by ZG
      expansion. The ZG is innervated by sympathetic, vasoactive intestinal polypeptide
      (VIP) and neuropeptide tyrosine (NPY), and sensory, calcitonin gene-related
      peptide, nerves. It is unclear whether innervation is affected by ZG growth.
      Therefore, we measured neurite outgrowth in the ZG of adult male rats after
      dietary sodium manipulation. In response to 1 wk sodium restriction, VIP and NPY
      fibers elongated in parallel with expansion of the ZG, shown by aldosterone
      synthase (AS) expression, but calcitonin gene-related peptide fibers were not
      affected. Sodium repletion resulted in parallel regression in VIP and NPY fiber
      length and AS expression. These results show that sympathetic, but not sensory,
      innervation is coordinated with ZG growth. Mediators underlying changes in
      innervation are unknown; therefore, we characterized a novel gene TMEM35 [termed
      the unknown factor-1 (TUF1) due to its unknown function] that shows extensive
      overlap with AS in ZG. After sodium restriction, TUF1 expanded in parallel with
      the ZG. TUF1 bound the low-affinity neurotrophin receptor, p75NTR, which was
      expressed in NPY fibers and showed a response similar to TUF1 after sodium
      manipulation. TUF1- p75NTR binding was competitively displaced by nerve growth
      factor but not by TUF1 lacking the p75NTR binding motif. Moreover, TUF1 mRNA in
      rat ZG cells increased after angiotensin II exposure in vitro. Collectively,
      these findings suggest that TMEM35/TUF1 is a candidate for modulating neurite
      outgrowth in the ZG after sodium depletion.

PMID- 20685869
TI  - Maternal high-fat diet alters methylation and gene expression of dopamine and
      opioid-related genes.
AB  - Maternal obesity during pregnancy increases the risk of obesity in the offspring.
      Obesity, arising from an imbalance of energy intake and expenditure, can be
      driven by the ingestion of palatable [high fat (HF), high sugar], energy-dense
      foods. Dopamine and opioid circuitry are neural substrates associated with reward
      that can affect animals' preference for palatable foods. Using a mouse model, the
      long-term effect of maternal consumption of a HF diet on dopamine and opioid gene
      expression within the mesocorticolimbic reward circuitry and hypothalamus of the
      offspring was investigated. Mice from dams fed a HF diet during pregnancy and
      lactation showed an increased preference for sucrose and fat. Gene expression,
      measured using quantitative real-time PCR, revealed a significant approximately 3
      to 10-fold up-regulation of dopamine reuptake transporter (DAT) in the ventral
      tegmental area, nucleus accumbens, and prefrontal cortex and a down-regulation of
      DAT in the hypothalamus. Additionally, expression of both MU-opioid receptor
      (MOR) and preproenkephalin (PENK) was increased in nucleus accumbens, prefrontal
      cortex, and hypothalamus of mice from dams that consumed the HF diet. Epigenetic
      mechanisms have been associated with long-term programming of gene expression
      after various in utero insults. We observed global and gene-specific (DAT, MOR,
      and PENK) promoter DNA hypomethylation in the brains of offspring from dams that
      consumed the HF diet. These data demonstrate that maternal consumption of a HF
      diet can change the offsprings' epigenetic marks (DNA hypomethylation) in
      association with long-term alterations in gene expression (dopamine and opioids)
      and behavior (preference for palatable foods).

PMID- 20685871
TI  - Inhaled insulin forms toxic pulmonary amyloid aggregates.
AB  - It is well known that interfaces, such as polar-nonpolar or liquid-air, play a
      key role in triggering protein aggregation in vitro, in particular the
      aggregation of peptides and proteins with the predisposition of misfolding and
      aggregation. Here we show that the interface present in the lungs predisposes the
      lungs to form aggregation of inhaled insulin. Insulin inhalers were introduced,
      and a large number of diabetic patients have used them. Although inhalers were
      safe and effective, decreases in pulmonary capacity have been reported in
      response to inhaled insulin. We hypothesize that the lung air-tissue interface
      provides a template for the aggregation of inhaled insulin. Our studies were
      designed to investigate the harmful potential that inhaled insulin has in
      pulmonary tissue in vivo, through an amyloid formation mechanism. Our data
      demonstrate that inhaled insulin rapidly forms amyloid in the lungs causing a
      significant reduction in pulmonary air flow. Our studies exemplify the importance
      that interfaces play in protein aggregation in vivo, illustrating the potential
      aggregation of inhaled proteins and the formation of amyloid deposits in the
      lungs. These insulin deposits resemble the amyloid structures implicated in
      protein misfolding disorders, such as Alzheimer's and Parkinson's diseases, and
      could as well be deleterious in nature.

PMID- 20685872
TI  - Identification and characterization of acyl-protein thioesterase
      1/lysophospholipase I as a ghrelin deacylation/lysophospholipid hydrolyzing
      enzyme in fetal bovine serum and conditioned medium.
AB  - Ghrelin contains an octanoic acid at the third residue serine, and the presence
      of octanoic acid on ghrelin is critical to its physiological functions. The
      precise mechanism for the deacylation of ghrelin in circulation remains to be
      clarified, although the level of deacylated ghrelin (des-acyl ghrelin) is higher
      than that of acylated ghrelin in serum. In this study, rapid identification of
      ghrelin deacylation activity was achieved by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry, and a ghrelin deacylation
      enzyme was purified 1515-fold from fetal bovine serum. Chromatographic separation
      showed a 24-kDa band on SDS-PAGE corresponding to ghrelin deacylation activity,
      and the protein band was identified as acyl-protein thioesterase 1
      (APT1)/lysophospholipase I. A ghrelin deacylation enzyme in medium from HepG2
      cells was also purified and identified as APT1. Although it lacks a secretion
      signal sequence, APT1 may be released by cells expressing APT1, mainly from liver
      in vivo. APT1 was originally purified as a cytosolic lysophospholipid hydrolyzing
      enzyme (lysophospholipase I), and recombinant APT1 exhibited deacylation activity
      as well as lysophospholipase activity in vitro. APT1 is released at high levels
      from RAW264.7 macrophage-like cells into the culture medium after stimulation
      with lipopolysaccharide (LPS), and LPS suppresses APT1 mRNA and protein
      expressions in these cells. More potent ghrelin deacylase activities were
      detected in sera from LPS-treated rats than in control sera. These results
      suggested that the serum activity of APT1 may play an important role in
      determination of the concentration of des-acyl ghrelin in circulation, especially
      under septic inflammation.

PMID- 20685873
TI  - Nocturnin suppresses igf1 expression in bone by targeting the 3' untranslated
      region of igf1 mRNA.
AB  - IGF-I is an anabolic factor that mediates GH and PTH actions in bone. Expression
      of skeletal Igf1 differs for inbred strains of mice, and Igf expression levels
      correlate directly with bone mass. Previously we reported that peroxisome
      proliferator-activated receptor-gamma2 activation in bone marrow suppressed Igf1
      expression and that peroxisome proliferator-activated receptor-gamma2 activation
      induced Nocturnin (Noc) expression, a circadian gene with peak expression at
      light offset, which functions as a deadenylase. In 24-h studies we found that
      Igf1 mRNA exhibited a circadian rhythm in femur with the lowest Igf1 transcript
      levels at night when Noc transcripts were highest. Immunoprecipitation/RT-PCR
      analysis revealed a physical interaction between Noc protein and Igf1
      transcripts. To clarify which portions of the Igf1 3' untranslated region (UTR)
      were necessary for regulation by Noc, we generated luciferase constructs
      containing various lengths of the Igf1 3'UTR. Noc did not affect the 170-bp short
      form 3'UTR, but suppressed luciferase activity in constructs bearing the longer
      form 3'UTR, which contains a number of potential regulatory motifs involved in
      mRNA degradation. C57BL/6J mice have low skeletal Igf1 mRNA compared with C3H/HeJ
      mice, and the Igf1 3' UTR is polymorphic between these strains. Interestingly,
      the activity of luciferase constructs bearing the long-form 3'UTR from C57BL/6J
      mice were repressed by Noc overexpression, whereas those bearing the
      corresponding region from C3H/HeJ were not. In summary, Noc interacts with Igf1
      in a strain- and tissue-specific manner and reduces Igf1 expression by targeting
      the longer form of the Igf1 3'UTR. Posttranscriptional regulation of Igf1 may be
      critically important during skeletal acquisition and maintenance.

PMID- 20685874
TI  - Production of proinflammatory cytokines and chemokines during neuroinflammation:
      novel roles for estrogen receptors alpha and beta.
AB  - Neuroinflammation is a common feature of many neurological disorders, and it is
      often accompanied by the release of proinflammatory cytokines and chemokines.
      Estradiol-17beta (E2) exhibits antiinflammatory properties, including the
      suppression of proinflammatory cytokines, in the central nervous system. However,
      the mechanisms employed by E2 and the role(s) of estrogen receptors (ERs) ERalpha
      and ERbeta are unclear. To investigate these mechanisms, we employed an in vivo
      lipopolysaccharide (LPS) model of systemic inflammation in ovariectomized (OVX)
      and OVX and E2-treated (OVX+E2) mice. Brain levels of proinflammatory cytokines
      (IL-1beta, IL-6, and IL-12p40) and chemokines (CCL2/MCP-1, CCL3/MIP-1alpha,
      CCL5/RANTES, and CXCL1/KC) were quantified in mice at 0 (sham), 3, 6, 12, and 24
      h after infection using multiplex protein analysis. E2 treatment inhibited LPS
      induced increases in all cytokines. In contrast, E2 treatment only suppressed
      CCL/RANTES chemokine concentrations. To determine whether ERalpha and ERbeta
      regulate brain cytokine and chemokine levels, parallel experiments were conducted
      using ERalpha knockout and ERbeta knockout mice. Our results revealed that both
      ERalpha and ERbeta regulated proinflammatory cytokine and chemokine production
      through E2-dependent and E2-independent mechanisms. To assess whether breakdown
      of the blood-brain barrier is an additional target of E2 against LPS-induced
      neuroinflammation, we measured Evan's blue extravasation and identified distinct
      roles for ERalpha and ERbeta. Taken together, these studies identify a dramatic
      cytokine- and chemokine-mediated neuroinflammatory response that is regulated
      through ERalpha- and ERbeta-mediated ligand-dependent and ligand-independent
      mechanisms.

PMID- 20685875
TI  - The receptor-dependent actions of 1,25-dihydroxyvitamin D are required for normal
      growth plate maturation in NPt2a knockout mice.
AB  - Rickets is a growth plate abnormality observed in growing animals and humans.
      Rachitic expansion of the hypertrophic chondrocyte layer of the growth plate, in
      the setting of hypophosphatemia, is due to impaired apoptosis of these cells.
      Rickets is observed in humans and mice with X-linked hypophosphatemia that is
      associated with renal phosphate wasting secondary to elevated levels of
      fibroblast growth factor-23. Rickets is also seen in settings of impaired vitamin
      D action, due to elevated PTH levels that increase renal phosphate excretion.
      However, mice with hypophosphatemia secondary to ablation of the renal sodium
      dependent phosphate transport protein 2a (Npt2a), have not been reported to
      develop rickets. Because activation of the mitochondrial apoptotic pathway by
      phosphate is required for hypertrophic chondrocyte apoptosis in vivo,
      investigations were undertaken to address this paradox. Analyses of the Npt2a
      null growth plate demonstrate expansion of the hypertrophic chondrocyte layer at
      2 wk of age, with resolution of this abnormality by 5 wk of age. This is
      temporally associated with an increase in circulating levels of 1,25
      dihydroxyvitamin D. To address whether the receptor-dependent actions of this
      steroid hormone are required for normalization of the growth plate phenotype, the
      Npt2a null mice were mated with mice lacking the vitamin D receptor or were
      rendered vitamin D deficient. These studies demonstrate that the receptor
      dependent actions of 1,25-dihydroxyvitamin D are required for maintenance of a
      normal growth plate phenotype in the Npt2a null mice.

PMID- 20685876
TI  - Glucagon-like peptide-1 receptor knockout mice are protected from high-fat diet
      induced insulin resistance.
AB  - Glucagon-like peptide-1 augments nutrient-stimulated insulin secretion. Chow-fed
      mice lacking the glucagon-like peptide-1 receptor (Glp1r) exhibit enhanced
      insulin-stimulated muscle glucose uptake but impaired suppression of endogenous
      glucose appearance (endoRa). This proposes a novel role for the Glp1r to regulate
      the balance of glucose disposal in muscle and liver by modulating insulin action.
      Whether this is maintained in an insulin-resistant state is unknown. The present
      studies tested the hypothesis that disruption of Glp1r expression overcomes high
      fat (HF) diet-induced muscle insulin resistance and exacerbates HF diet-induced
      hepatic insulin resistance. Mice with a functional disruption of the Glp1r (Glp1r
      /-) were compared with wild-type littermates (Glp1r+/+) after 12 wk on a regular
      chow diet or a HF diet. Arterial and venous catheters were implanted for sampling
      and infusions. Hyperinsulinemic-euglycemic clamps were performed on weight
      matched male mice. [3-(3)H]glucose was used to determine glucose turnover, and
      2[14C]deoxyglucose was used to measure the glucose metabolic index, an indicator
      of glucose uptake. Glp1r-/- mice exhibited increased glucose disappearance and
      muscle glucose metabolic index on either diet. This was associated with enhanced
      activation of muscle Akt and AMP-activated protein kinase and reduced muscle
      triglycerides in HF-fed Glp1r-/- mice. Chow-fed Glp1r-/- mice exhibited impaired
      suppression of endoRa and hepatic insulin signaling. In contrast, HF-fed Glp1r-/-
      mice exhibited improved suppression of endoRa and hepatic Akt activation. This
      was associated with decreased hepatic triglycerides and impaired activation of
      sterol regulatory element-binding protein-1. These results show that mice lacking
      the Glp1r are protected from HF diet-induced muscle and hepatic insulin
      resistance independent of effects on total fat mass.

PMID- 20685877
TI  - Dual targeting of tumor and endothelial cells by gonadotropin-releasing hormone
      agonists to reduce melanoma angiogenesis.
AB  - We showed previously that GnRH receptors are expressed in melanoma cells; their
      activation reduces cell growth and metastatic behavior. Here, we investigated
      whether GnRH agonists might affect the expression of genes involved in melanoma
      progression. By genome-wide transcriptomic and real-time PCR analysis, we first
      observed that GnRH agonists decrease the expression of the pro-angiogenic factor
      vascular endothelial growth factor (VEGF) (all isoforms) in BLM melanoma cells.
      Then, we demonstrated that GnRH agonists specifically decrease the expression of
      the VEGF165 isoform as well as its secretion from BLM cells. These data suggested
      that activation of GnRH receptors might reduce the pro-angiogenic behavior of
      melanoma cells. To verify this hypothesis, we treated BLM cells with a GnRH
      agonist; the conditioned medium from these cells was tested to assess its
      capability to stimulate human umbilical vein endothelial cell (HUVEC) motility.
      The migration of HUVECs towards the conditioned medium of GnRH agonist-treated
      BLM cells was significantly lower than the migration of HUVECs toward the
      conditioned medium of untreated cells. Thus, GnRH agonists reduce the pro
      angiogenic behavior of melanoma cells through a decreased production of bioactive
      VEGF. We then found that GnRH receptors are also expressed on HUVECs and that
      GnRH agonists reduce their ability to proliferate and to form capillary-like
      tubes when stimulated by VEGF. These findings suggest that GnRH agonists exert an
      anti-angiogenic activity indirectly by decreasing VEGF secretion from tumor cells
      and directly by counteracting the pro-angiogenic activity of the growth factor.
      These data might lead to the development of novel targeted approaches for
      melanoma.

PMID- 20685878
TI  - Molecular, immunohistochemical, and pharmacological evidence of oxytocin's role
      as inhibitor of carbohydrate but not fat intake.
AB  - Oxytocin (OT) facilitates feeding termination stemming from high osmolality,
      stomach distention, and malaise. Recent knockout (KO) studies suggested a crucial
      function for OT in carbohydrate intake: OT-/- mice had increased preference for
      carbohydrates, including sucrose, but not fat (Intralipid). In striking contrast,
      sugar appetite was unaffected in the OT receptor KO mouse; data from wild-type
      animals have been insufficient. Therefore, we examined the involvement of OT in
      the regulation of sucrose vs. fat intake in C57BL/6 mice that served as a
      background KO strain. We exposed mice to a meal of sucrose or Intralipid and
      determined that the percentage of c-Fos-immunoreactive paraventricular
      hypothalamic OT neurons was elevated at termination of intake of either of the
      tastants, but this increase was 2-fold higher in sucrose-fed mice. A 48-h
      exposure to sucrose compared with Intralipid caused up-regulation of OT mRNA,
      whereas inherent individual preferences for sucrose vs. fat were not associated
      with differences in baseline OT expression as established with quantitative PCR.
      We found that L-368,899, an OT receptor antagonist, increased sugar intake when
      sucrose was presented alone or concurrently with Intralipid; it had no effect on
      Intralipid or total calorie consumption. L-368,899 affected Fos immunoreactivity
      in the paraventricular hypothalamus, arcuate nucleus, amygdala, and nucleus of
      the solitary tract, areas involved in aversion, satiety, and reward. This pattern
      serves as neuroanatomical basis of OT's complex role in food intake, including
      sucrose intake. The current findings expand our knowledge on OT and suggest that
      it acts as a carbohydrate-specific inhibitor of feeding.

PMID- 20685879
TI  - An inositol 1,4,5-triphosphate (IP3)-IP3 receptor pathway is required for insulin
      stimulated glucose transporter 4 translocation and glucose uptake in
      cardiomyocytes.
AB  - Intracellular calcium levels ([Ca2+]i) and glucose uptake are central to
      cardiomyocyte physiology, yet connections between them have not been studied. We
      investigated whether insulin regulates [Ca2+]i in cultured cardiomyocytes, the
      participating mechanisms, and their influence on glucose uptake via SLC2 family
      of facilitative glucose transporter 4 (GLUT4). Primary neonatal rat
      cardiomyocytes were preloaded with the Ca2+ fluorescent dye fluo3-acetoxymethyl
      ester compound (AM) and visualized by confocal microscopy. Ca2+ transport
      pathways were selectively targeted by chemical and molecular inhibition. Glucose
      uptake was assessed using [3H]2-deoxyglucose, and surface GLUT4 levels were
      quantified in nonpermeabilized cardiomyocytes transfected with GLUT4-myc-enhanced
      green fluorescent protein. Insulin elicited a fast, two-component, transient
      increase in [Ca2+]i. Nifedipine and ryanodine prevented only the first component.
      The second one was reduced by inositol-1,4,5-trisphosphate (IP3)-receptor
      selective inhibitors (xestospongin C, 2 amino-ethoxydiphenylborate), by type 2
      IP3 receptor knockdown via small interfering RNA or by transfected Gbetagamma
      peptidic inhibitor betaARKct. Insulin-stimulated glucose uptake was prevented by
      bis(2-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid-AM, 2-amino
      ethoxydiphenylborate, and betaARK-ct but not by nifedipine or ryanodine.
      Similarly, insulin-dependent exofacial exposure of GLUT4-myc-enhanced green
      fluorescent protein was inhibited by bis(2-aminophenoxy)ethane-N,N,N',N'-tetra
      acetic acid-AM and xestospongin C but not by nifedipine. Phosphatidylinositol 3
      kinase and Akt were also required for the second phase of Ca2+ release and GLUT4
      translocation. Transfected dominant-negative phosphatidylinositol 3-kinase gamma
      inhibited the latter. In conclusion, in primary neonatal cardiomyocytes, insulin
      induces an important component of Ca2+ release via IP3 receptor. This component
      signals to glucose uptake via GLUT4, revealing a so-far unrealized contribution
      of IP3-sensitive Ca2+ stores to insulin action. This pathway may influence
      cardiac metabolism in conditions yet to be explored in adult myocardium.

PMID- 20685881
TI  - Peripheral serotonin enhances lipid metabolism by accelerating bile acid
      turnover.
AB  - Serotonin is synthesized by two distinct tryptophan hydroxylases, one in the
      brain and one in the periphery. The latter is known to be unable to cross the
      blood-brain barrier. These two serotonin systems have apparently independent
      functions, although the functions of peripheral serotonin have yet to be fully
      elucidated. In this study, we have investigated the physiological effect of
      peripheral serotonin on the concentrations of metabolites in the circulation and
      in the liver. After fasting, mice were ip injected with 1 mg serotonin. The
      plasma glucose concentration was significantly elevated between 60 and 270 min
      after the injection. In contrast, plasma triglyceride, cholesterol, and
      nonesterified fatty acid concentrations were decreased. The hepatic glycogen
      synthesis and concentrations were significantly higher at 240 min. At the same
      time, the hepatic triglyceride content was significantly lower than the basal
      levels noted before the serotonin injection, whereas the hepatic cholesterol
      content was significantly higher by 60 min after the injection. Furthermore,
      serotonin stimulated the contraction of the gallbladder and the excretion of
      bile. After the serotonin injection, there was a significant induction of apical
      sodium-dependent bile acid transporter expression, resulting in a decrease in the
      concentration of bile acids in the feces. Additionally, data are presented to
      show that the functions of serotonin are mediated through diverse serotonin
      receptor subtypes. These data indicate that peripheral serotonin accelerates the
      metabolism of lipid by increasing the concentration of bile acids in circulation.

PMID- 20685880
TI  - Modulation of gonadotropin-releasing hormone-induced extracellular signal
      regulated kinase activation by dual-specificity protein phosphatase 1 in LbetaT2
      gonadotropes.
AB  - As the regulator of pituitary reproductive hormone synthesis, the hypothalamic
      neuropeptide GnRH is the central regulator of reproduction. A hallmark of GnRH
      action is the differential control of gene expression in pituitary gonadotropes
      through varied pulsatile stimulation. Among other signaling events, GnRH
      activation of the ERK family of MAPKs plays a significant role in the
      transcriptional regulation of the luteinizing hormone beta-subunit gene and
      regulation of cap-dependent translation. We evaluated the ERK response to
      different GnRH pulse amplitudes in the gonadotrope cell line LbetaT2. We found
      that low-amplitude stimulation with GnRH invokes a rapid and transient ERK
      activation, whereas high-amplitude stimulation invokes a prolonged activation
      specifically in the cytoplasm fraction of LbetaT2 cells. Nuclear and cytoplasmic
      targets of ERK, Ets-like gene 1, and eukaryotic initiation factor 4E,
      respectively, are similarly activated. Feedback control of ERK activation occurs
      mainly through the dual-specificity protein phosphatases (DUSPs). DUSP1 is
      localized to the nucleus in LbetaT2 cells but DUSP4, another member implicated in
      GnRH feedback, exists in both the nucleus and cytoplasm. Manipulation of nuclear
      DUSP activity through overexpression or knockdown of Dusp1 modulates the ERK
      response to low and high GnRH pulse amplitudes and activation of the Lhb
      promoter. Dusp1 overexpression abolishes sustained ERK activation and inhibits
      Lhb promoter activity induced by high amplitude pulses. Conversely, Dusp1
      knockdown enhances ERK activation by low-amplitude stimulation and increases
      stimulation of Lhb promoter activity. We conclude that DUSP1 feedback activity
      modulates ERK activation and the transcriptional response to GnRH.

PMID- 20685882
TI  - The endogenous actions of hypothalamic peptides on brown adipose tissue
      thermogenesis in the rat.
AB  - Although the neuronal pathways within the hypothalamus critical in controlling
      feeding and energy expenditure and projecting to brown adipose tissue (BAT) have
      been identified and their peptidergic content characterized, endogenous action of
      such peptides in the control of BAT activity has not been elucidated. Here male
      Sprague Dawley rats received infusions of either melanin-concentrating hormone
      antagonist (SNAP-7941) (1 microg/microl x h), orexin A receptor antagonist (SB
      334867-A; 1 microg/microl x h), combined SB-334867-A (1 microg/microl x h), and
      SNAP-7941 (1 microg/microl x h), or melanocortin-3/4 receptor antagonist
      (SHU9119) (1 microg/microl x h) via an indwelling cannula in the lateral
      ventricle attached to s.c. implanted osmotic minipump. BAT temperature, physical
      activity, body weight, food intake, and changes in uncoupling protein (UCP)-1
      were measured. SB-334867-A and SNAP-7941 significantly increased BAT temperature
      and UCP1 expression and reduced food intake and body weight. Combined infusion of
      SB-334867-A and SNAP-7941 produced a pronounced response that was greater than
      the addition of the individual effects in all parameters measured. SHU9119
      significantly decreased BAT temperature and UCP1 expression and increased feeding
      and body weight. In a second series of experiments, the effect of SB-334867-A and
      SNAP-7941 alone or combination on the expression of the Fos protein was
      determined. SB-334867-A and SNAP-7941 increased Fos expression in key
      hypothalamic and brainstem feeding-related regions. In combination, these
      antagonists produced a greater than additive elevation of Fos expression in most
      of the regions evaluated. These findings support a role for endogenous orexigenic
      and anorexigenic hypothalamic peptides acting in concert to create a thermogenic
      tone via BAT activity.

PMID- 20685883
TI  - Update on estrogens and the skeleton.
AB  - CONTEXT: The very clinical trial, the Women's Health Initiative, which definitely
      established the antifracture efficacy of estrogen therapy, led to the demise of
      estrogen treatment as a viable, long-term option for prevention of bone loss in
      postmenopausal women due to the well-publicized adverse effects of estrogen plus
      progestin therapy on a number of nonskeletal endpoints. Given the diminishing
      clinical use of estrogen, it is logical to question whether estrogen regulation
      of bone remains a relevant issue at a clinical or basic research level. EVIDENCE
      ACQUISITION: Findings of this update are based on a PubMed search and the
      author's knowledge of the field. EVIDENCE SYNTHESIS: Basic and clinical studies
      on the mechanisms of estrogen effects on bone will continue to provide potential
      novel drug targets for the prevention and treatment of osteoporosis. At a
      clinical level, it is clear that even the low levels of estrogen present in
      postmenopausal women have a significant impact on bone turnover, leading to a
      more aggressive approach to prevent bone loss in patients with breast cancer on
      aromatase inhibitors. Conversely, increasing these low estrogen levels with small
      doses of estrogen may have beneficial skeletal effects in postmenopausal women
      without adverse effects on reproductive tissues. Finally, the search continues
      for new selective estrogen receptor modulators with beneficial effects on bone
      and other tissues. CONCLUSIONS: Even in the post-WHI era, basic and clinical
      investigation on estrogen and bone will continue to yield important insights that
      not only expand our knowledge at a basic level but also impact the health of our
      aging population.

PMID- 20685884
TI  - Approach to the patient with diabetes during pregnancy.
AB  - The epidemics of obesity and type 2 diabetes mellitus (T2DM) globally are
      paralleling an increase in the number of women with T2DM becoming pregnant.
      Because T2DM is frequently undiagnosed before pregnancy, the risk of major
      malformations in the developing fetus is increased due to uncontrolled
      hyperglycemia. The lack of preconception care and the increase in complications
      of pregnancy due to the coexistence of obesity and T2DM are of concern from both
      an individual and a public health standpoint. Rapid achievement of normoglycemia
      with limited weight gain is critical to optimize maternal and fetal outcomes in
      all women with diabetes during pregnancy, regardless of the type of diabetes.
      This article will focus on T2DM preceding pregnancy due to its increasing
      prevalence and potentially dire fetal and maternal consequences. Euglycemia
      before, during, and after all pregnancies complicated by diabetes results in the
      best opportunity for optimal outcomes for mother and infant.

PMID- 20685885
TI  - Approach to the patient with incidental papillary microcarcinoma.
AB  - Analysis of the Surveillance Epidemiology and End Results database reveals that
      since 1995 a 2.4-fold increase in thyroid cancer has occurred. A concomitant rise
      in cases of thyroid microcarcinoma has also been noted, with the frequency rising
      by approximately 50% as well. Increased detection of thyroid nodules, many of
      them below 1 cm in size, is at least partly responsible for this trend. The wide
      use of sensitive imaging modalities for various indications leads to the
      incidental discovery of thyroid nodules, some of which contain thyroid cancer,
      including cases of microcarcinoma. Although the vast majority of patients with
      thyroid cancer foci smaller than 1 cm will do exceedingly well long term,
      exceptions do occur, with some patients experiencing recurrence either locally or
      less frequently with distant metastasis. There has been some debate on the
      optimal management for these patients to include: extent of surgery required, the
      usefulness of ablation with radioactive iodine, as well as the optimal level for
      TSH suppression. In this article, we will review the available data and
      recommendations surrounding the management of patients with incidental thyroid
      microcarcinoma.

PMID- 20685886
TI  - Cystic degeneration of macroprolactinoma on long-term cabergoline.

PMID- 20685887
TI  - Duplication of the pituitary stalk in a patient with a heterozygous deletion of
      chromosome 14 harboring the thyroid transcription factor-1 gene.
AB  - Magnetic resonance imaging of the hypothalamic-pituitary region revealed a
      duplication of the pituitary stalk in a patient with a heterozygous deletion of
      chromosome 14 harboring the thyroid transcription factor-1 gene.

PMID- 20685888
TI  - A case of adrenocortical oncocytoma occurring with aldosteronoma.

PMID- 20685889
TI  - Cognitive function in subclinical hypothyroidism.

PMID- 20685890
TI  - Thyroid and obesity: an intriguing relationship.

PMID- 20685891
TI  - On the trail of the SBP2-syndrome: clues in a Daedalean maze.

PMID- 20685892
TI  - Identification of zyklopen, a new member of the vertebrate multicopper
      ferroxidase family, and characterization in rodents and human cells.
AB  - We previously detected a membrane-bound, copper-containing oxidase that may be
      involved in iron efflux in BeWo cells, a human placental cell line. We have now
      identified a gene encoding a predicted multicopper ferroxidase (MCF) with a
      putative C-terminal membrane-spanning sequence and high sequence identity to
      hephaestin (Heph) and ceruloplasmin (Cp), the other known vertebrate MCF.
      Molecular modeling revealed conservation of all type I, II, and III copper
      binding sites as well as a putative iron-binding site. Protein expression was
      observed in multiple diverse mouse tissues, including placenta and mammary gland,
      and the expression pattern was distinct from that of Cp and Heph. The protein
      possessed ferroxidase activity, and protein levels decreased in cellular copper
      deficiency. Knockdown with small interfering RNA in BeWo cells indicates that
      this gene represents the previously detected oxidase. We propose calling this new
      member of the MCF family "zyklopen."

PMID- 20685893
TI  - Luteolin inhibits microglia and alters hippocampal-dependent spatial working
      memory in aged mice.
AB  - A dysregulated overexpression of inflammatory mediators by microglia may
      facilitate cognitive aging and neurodegeneration. Considerable evidence suggests
      the flavonoid luteolin has antiinflammatory effects, but its ability to inhibit
      microglia, reduce inflammatory mediators, and improve hippocampal-dependent
      learning and memory in aged mice is unknown. In initial studies, pretreatment of
      BV-2 microglia with luteolin inhibited the induction of inflammatory genes and
      the release of inflammatory mediators after lipopolysaccharide (LPS) stimulation.
      Supernatants from LPS-stimulated microglia caused discernible death in Neuro.2a
      cells. However, treating microglia with luteolin prior to LPS reduced neuronal
      cell death caused by conditioned supernatants, indicating luteolin was
      neuroprotective. In subsequent studies, adult (3-6 mo) and aged (22-24 mo) mice
      were fed control or luteolin (20 mg/d)-supplemented diet for 4 wk and spatial
      working memory was assessed as were several inflammatory markers in the
      hippocampus. Aged mice fed control diet exhibited deficits in spatial working
      memory and expression of inflammatory markers in the hippocampus indicative of
      increased microglial cell activity. Luteolin consumption improved spatial working
      memory and restored expression of inflammatory markers in the hippocampus
      compared with that of young adults. Luteolin did not affect either spatial
      working memory or inflammatory markers in young adults. Taken together, the
      current findings suggest dietary luteolin enhanced spatial working memory by
      mitigating microglial-associated inflammation in the hippocampus. Therefore,
      luteolin consumption may be beneficial in preventing or treating conditions
      involving increased microglial cell activity and inflammation.

PMID- 20685894
TI  - Visible drug delivery by supramolecular nanocarriers directing to single
      platformed diagnosis and therapy of pancreatic tumor model.
AB  - Nanoparticle therapeutics are promising platforms for cancer therapy. However, it
      remains a formidable challenge to assess their distribution and clinical efficacy
      for therapeutic applications. Here, by using multifunctional polymeric micellar
      nanocarriers incorporating clinically approved gadolinium (Gd)-based magnetic
      resonance imaging contrast agents and platinum (Pt) anticancer drugs through
      reversible metal chelation of Pt, simultaneous imaging and therapy of an
      orthotopic animal model of intractable human pancreatic tumor was successfully
      performed without any serious toxicity. The strong tumor contrast enhancement
      achieved by the micelles correlated with the 24 times increase of r(1) of the Gd
      chelates, the highest for the formulations using clinically approved Gd chelates
      reported to date. From the micro-synchrotron radiation X-ray fluorescence
      spectrometry scanning of the lesions, we confirmed that both the Gd chelates and
      Pt drugs delivered by the micelles selectively colocalized in the tumor interior.
      Our study provides new insights for the design of theranostic micelles with high
      contrast enhancement and site-specific clinical potential.

PMID- 20685895
TI  - Coactivated platelet-derived growth factor receptor {alpha} and epidermal growth
      factor receptor are potential therapeutic targets in intimal sarcoma.
AB  - Intimal sarcoma (IS) is a rare, malignant, and aggressive tumor that shows a
      relentless course with a concomitant low survival rate and for which no effective
      treatment is available. In this study, 21 cases of large arterial blood vessel IS
      were analyzed by immunohistochemistry and fluorescence in situ hybridization and
      selectively by karyotyping, array comparative genomic hybridization, sequencing,
      phospho-kinase antibody arrays, and Western immunoblotting in search for novel
      diagnostic markers and potential molecular therapeutic targets. Ex vivo
      immunoassays were applied to test the sensitivity of IS primary tumor cells to
      the receptor tyrosine kinase (RTK) inhibitors imatinib and dasatinib. We showed
      that amplification of platelet-derived growth factor receptor alpha (PDGFRA) is a
      common finding in IS, which should be considered as a molecular hallmark of this
      entity. This amplification is consistently associated with PDGFRA activation.
      Furthermore, the tumors reveal persistent activation of the epidermal growth
      factor receptor (EGFR), concurrent to PDGFRA activation. Activated PDGFRA and
      EGFR frequently coexist with amplification and overexpression of the MDM2
      oncogene. Ex vivo immunoassays on primary IS cells from one case showed the
      potency of dasatinib to inhibit PDGFRA and downstream signaling pathways. Our
      findings provide a rationale for investigating therapies that target PDGFRA,
      EGFR, or MDM2 in IS. Given the clonal heterogeneity of this tumor type and the
      potential cross-talk between the PDGFRA and EGFR signaling pathways, targeting
      multiple RTKs and aberrant downstream effectors might be required to improve the
      therapeutic outcome for patients with this disease.

PMID- 20685896
TI  - The swine flu scam?

PMID- 20685897
TI  - Mixtard 30 - going, going, gone?

PMID- 20685898
TI  - Ulipristal - a new emergency contraceptive pill.
AB  - Until recently, women in the UK who wanted emergency contraception had two
      options: an oral hormonal method (levonorgestrel), which is licensed for use up
      to 3 days after unprotected sexual intercourse; or a copper-bearing intrauterine
      device (IUD), which can be inserted up to 5 days after unprotected intercourse or
      up to 5 days after the earliest likely calculated ovulation. Now ulipristal
      acetate (ellaOne - HRA Pharma), a new oral hormonal emergency contraceptive, has
      been licensed in the European Union for use within 120 hours (5 days) of
      unprotected intercourse. Here we assess whether it is an advance for emergency
      contraception.

PMID- 20685899
TI  - Management of fibromyalgia.
AB  - Around 1 in 25 of the UK population has fibromyalgia, a lifelong condition
      involving widespread musculoskeletal pain and tenderness, fatigue, sleep
      disturbance, and functional impairment, without any known structural or
      inflammatory cause. This problem is costly in terms of consultations,
      prescriptions and sick leave. The main aims of therapy are to reduce symptoms, to
      improve function, and to help patients adapt to the condition. Here we consider
      the management of adults with fibromyalgia.

PMID- 20685900
TI  - Agomelatine for major depressive episodes.
AB  - Agomelatine (Valdoxan - Servier) is an antidepressant licensed for treating
      patients with major depressive episodes. The drug company's website for
      agomelatine states that the drug acts simultaneously as a melatonin receptor
      agonist and a serotonin receptor antagonist and claims that it is a "major
      therapeutic advance in management of depression through the restoration of
      circadian rhythms". Here we consider whether agomelatine offers significant
      advantage for patients with major depressive episodes.

PMID- 20685901
TI  - Psychometric properties of three instruments to measure fatigue with myocardial
      infarction.
AB  - The purpose of this study was to evaluate the psychometric properties of three
      questionnaires to measure fatigue with myocardial infarction. The Fatigue Symptom
      Inventory Interference Scale, Profile of Moods States Fatigue subscale (POMS-F),
      and Short Form 36 (SF-36) Vitality Scale were completed during hospitalization (n
      = 116) and 30 days after hospital admission (n = 49). Moderate to strong
      correlations were found among each of these fatigue scales and between each
      fatigue scale and measures of other variables to include vigor, depressed mood,
      anxiety, and physical functioning. POMS-F scores decreased significantly at Time
      2, but this decline in fatigue was not validated on the other fatigue scales.
      Patients' Time 1 scores reflected significantly more fatigue compared to
      published scores for healthy adults. The ability to discriminate between groups
      suggests that the instruments may be useful for identifying patients with
      cardiovascular risk factors who report clinically significant fatigue.

PMID- 20685902
TI  - Still smoking after all these years.

PMID- 20685903
TI  - Smoking identities and behavior: evidence of discrepancies, issues for
      measurement and intervention.
AB  - Although researchers and health care practitioners tend to use standard
      categories to classify smokers and nonsmokers, recent research suggests that
      individual smokers may use a variety of self-definitions regarding their smoking
      behavior. The purpose of this study was to examine smoking identity and smoking
      behavior among college students, specifically, the relationship between self
      identifying as a smoker, nonsmoker, occasional smoker, or social smoker and
      number of days smoked in the past month. Data were obtained during a campuswide
      health assessment of randomly selected full-time students (N = 741). Results
      indicate discrepancy between smoking identity and cigarette use. Twenty percent
      of students who smoked in the past 30 days self-identified as nonsmokers. Such
      discrepancies have implications for data collection in research as well as on
      questionnaires and in health care interviews. Failure to understand actual
      smoking behavior may increase the risk that individuals will not receive
      effective smoking prevention and cessation interventions.

PMID- 20685904
TI  - Anemia evaluation and management in nursing home residents.
AB  - Anemia is often an unrecognized and/or undertreated diagnosis in older adults.
      Failure to diagnose anemia leads to delayed treatment and thus delayed relief of
      symptoms. Given the potentially significant impact of anemia on cardiovascular
      disease and physical performance among older nursing home (NH) residents, it is
      important to evaluate current clinical practice related to anemia.The purpose of
      this secondary data analysis was to evaluate the frequency of laboratory
      evaluation and medication treatment for anemia among older NH residents. Results
      indicated that more than half of NH residents were anemic at baseline, and of
      those, less than 20% had additional testing done to further evaluate for an
      underlying cause of their anemia and only 45.3% received any pharmacologic
      treatment. Future research is needed to clarify the potential benefits of timely
      diagnosis and appropriate treatment for anemic older adults in long-term-care
      settings and establish evidence-based guidelines to direct care in this area.

PMID- 20685905
TI  - Connectedness in community-dwelling older adults.
AB  - The purpose of this study was to examine the processes involved with
      connectedness in community-dwelling older adults, which the authors contend is
      quality of life from a generative perspective. Using a grounded theory approach,
      12 older adults were interviewed using a semistructured interview guide. The tape
      recorded interviews were transcribed verbatim, categories were created to code
      the data, and themes were extracted. Four processes involved with connectedness
      in older adults were identified: (a) having something to do, (b) having
      relationships, (c) having a stake in the future, and (d) having a sense of
      continuity. Various aspects of spirituality were also apparent in each of the
      four processes. This study suggests that connectedness provides older adults with
      a mechanism to engage life in meaningful, positive, and purposeful ways.

PMID- 20685906
TI  - Experiencing and managing urinary incontinence: a qualitative study.
AB  - Urinary incontinence is a complex problem from which millions of people are
      affected worldwide. How the affected persons experience and organize their day-to
      day lives has hardly been studied. This was the motive for a 2(1/2)-year study in
      the German-speaking region. Thirty-two problem-centered interviews were conducted
      with 22 women and 10 men, which were then analyzed using the grounded theory
      method, after Strauss and Corbin. The experience of urinary incontinence is
      dependent on the cause of the incontinence and on whether the episode of
      incontinence took place in private or in public. Incontinence itself influences
      social, cultural, and sportive activities and partner relationships. The results
      show that persons with incontinence use complex strategies to regain control.
      These include (a) being prepared for the next urge to urinate or the next episode
      of incontinence, (b) searching for possible therapies, and (c) forming a circle
      of trust.

PMID- 20685907
TI  - Responses to work complexity: the novice to expert effect.
AB  - The purpose of this study was to explore the differences in how advanced
      beginners, competent, and expert nurses prioritize and reprioritize patient care.
      This qualitative study had a purposive sample of 23 nurses on cardiac/ telemetry
      units at five hospitals. Four themes emerged from the data: cognitive strategies,
      communication, integration of roles, and response to the work environment. As the
      nurses progressed in expertise, they were better able to organize, more
      effectively deal with interruptions, anticipate patient needs, integrate varied
      nursing roles into their work, and communicate effectively. The significance of
      this study is the identification of factors that affect the nurse's ability to
      work productively in today's care environment. It increases understanding of the
      graduate nurses' perception and response to the complexity and work of nursing.
      An understanding of these factors provides the basis for further research to
      understand and promote transition of nurses from advanced beginner to expert.

PMID- 20685908
TI  - Analysis of weight control in Korean adolescents using the transtheoretical
      model.
AB  - The purpose of this study was to identify the stages of change, the processes of
      change, and the decisional balance for weight control, self-efficacy, and other
      weight control-related variables and to determine the significant factors
      explaining movements between the stages of change in Korean adolescents. A total
      of 475 adolescents completed questionnaires and anthropometric measures. The
      majority of the adolescents were in the precontemplation (42.1%) and
      contemplation (43.0%) stages. The benefits of weight control (pros), desire for
      weight change, perceived body shape, and past experience with weight control
      increased the odds ratio of movement from precontemplation to contemplation.
      Stimulus control, self-reevaluation, regular exercise, and past experience of
      weight control significantly influenced the movement to action and maintenance
      from contemplation. The study results suggest that weight control programs should
      emphasize significant factors to help adolescents move through the stages of
      change.

PMID- 20685909
TI  - Job satisfaction ratings: measurement equivalence across nurses and physicians.
AB  - The measurement equivalence of job satisfaction ratings from physicians and
      nurses working in intensive care units was tested in the present study. Seventy
      two nurses and 72 physicians completed the Safety Attitudes Questionnaire, which
      contains five items about job satisfaction. Measurement equivalence across nurses
      and physicians of the job satisfaction ratings was examined via multiple-group
      confirmatory factor analysis. The results indicated that physicians and nurses
      use the same metric when providing ratings for this job satisfaction measure. The
      primary implication from the present study is that nurses and physicians
      conceptualize job satisfaction in a similar manner. This implication needs to be
      extended to other survey measures of interest to health services researchers.
      Future areas of research are discussed.

PMID- 20685910
TI  - Menopausal symptoms among four major ethnic groups in the United States.
AB  - The purpose of the study was to explore ethnic differences in symptoms
      experienced during the menopausal transition among four major ethnic groups in
      the United States. This study was done via a cross-sectional Internet survey
      among 512 midlife women recruited using a convenience sampling. The instruments
      included questions on background characteristics, ethnicity-related factors,
      health, and menopausal status and the Midlife Women's Symptom Index. The data
      were analyzed using descriptive and inferential statistics. Significant ethnic
      differences were found in the total number and severity of the symptoms. The most
      frequently reported symptoms and predictors of the total number and severity of
      the symptoms differed by ethnic identity. More in-depth cultural studies are
      needed to understand the reasons for the ethnic differences in menopausal symptom
      experience.

PMID- 20685911
TI  - Improving foodborne illness prevention among transplant recipients.
AB  - The U.S. Department of Agriculture developed a food safety brochure to educate
      transplant recipients and their caregivers about the risk of contracting
      foodborne illnesses and safe food-handling prevention practices. Qualitative
      research was conducted with transplant recipients and caregivers to collect
      information on participants' food safety concerns, knowledge, and practices;
      changes in food safety knowledge and practices after receiving the food safety
      brochure; preferred communication channels and dissemination strategies for
      delivering the brochure; and evaluation of the brochure. Many participants
      received food safety information from a health care provider, but the content and
      format varied by institution. Most participants are not following recommended
      practices to cook and chill food safely, and many participants consume high-risk
      foods associated with foodborne illnesses. After reading the brochure, many
      participants made or plan to make at least one food safety recommendation. The
      research findings were used to refine the brochure before nationwide
      distribution.

PMID- 20685912
TI  - Time banking and health: the role of a community currency organization in
      enhancing well-being.
AB  - Time banking is an international movement that seeks to transform traditional
      asymmetric social service models into social networks in which members both
      provide and receive services that are assigned equal value. Time banks have been
      shown to enhance social capital, and there is some evidence for improved health.
      This article, based on a survey of 160 members of a hospital-affiliated time
      bank, examines the likelihood and predictors of improvement in physical and
      mental health as a result of membership. Men, people with lower income, and those
      who were not working full-time reported highest levels of participation in
      exchanging services; attachment to the organization was greatest among women,
      older members, people with less education, and those with the highest
      participation levels. Multivariate analyses revealed that physical health
      improvement attributed to membership was significantly predicted by attachment to
      the organization and living alone; mental health gains were predicted by general
      health changes, average number of exchanges, and attachment to the organization.
      We conclude that a sense of belonging, a dimension of social capital, is key to
      improved well-being and that time banking may be particularly valuable in
      promoting health and belonging among older and lower-income individuals and those
      who live alone.

PMID- 20685913
TI  - Project GRACE: a staged approach to development of a community-academic
      partnership to address HIV in rural African American communities.
AB  - The HIV epidemic is a health crisis in rural African American communities in the
      Southeast United States; however, to date little attention has been paid to
      community-academic collaborations to address HIV in these communities.
      Interventions that use a community-based participatory research (CBPR) approach
      to address individual, social, and physical environmental factors have great
      potential for improving community health. Project GRACE (Growing, Reaching,
      Advocating for Change and Empowerment) uses a CBPR approach to develop culturally
      sensitive, feasible, and sustainable interventions to prevent the spread of HIV
      in rural African American communities. This article describes a staged approach
      to community-academic partnership: initial mobilization, establishment of
      organizational structure, capacity building for action, and planning for action.
      Strategies for engaging rural community members at each stage are discussed;
      challenges faced and lessons learned are also described. Careful attention to
      partnership development has resulted in a collaborative approach that has
      mutually benefited both the academic and community partners.

PMID- 20685914
TI  - Scoring subjectivity and item performance on measures used to assess violence
      risk: the PCL-R and HCR-20 as exemplars.
AB  - Although reliability is essential to validity, most research on violence risk
      assessment tools has paid little attention to strategies for improving rater
      agreement. The authors evaluated the degree to which perceived subjectivity in
      scoring guidelines for items from two measures-the Psychopathy Checklist-Revised
      (PCL-R) and the Historical, Clinical, Risk Management-20 (HCR-20)-were related to
      indices of interrater agreement reported in the research literature. Nine
      doctoral students with experience scoring the PCL-R and HCR-20 showed a high
      level of agreement with respect to the amount of subjectivity required to score
      items. Decreased subjectivity was associated with increased rater agreement for
      both tools. For the PCL-R, items on aggregate measures that have the strongest
      effects in predictive validity research (i.e., Factor 2, Facet 4) were rated as
      the least subjective. For the HCR-20, items on the Historical scale were rated as
      the least subjective. Implications for measure development and refinement are
      discussed.

PMID- 20685915
TI  - Novel laboratory mouse papillomavirus (MusPV) infection.
AB  - Most papillomaviruses (PVs) are oncogenic. There are at least 100 different human
      PVs and 65 nonhuman vertebrate hosts, including wild rodents, which have species
      specific PV infections. Florid papillomatosis arose in a colony of NMRI
      Foxn1(nu)/Foxn1(nu) (nude) mice at the Advanced Centre for Treatment Research and
      Education in Cancer in India. Lesions appeared at the mucocutaneous junctions of
      the nose and mouth. Histologically, lesions were classical papillomas with
      epidermal hyperplasia on thin fibrovascular stalks in a verrucous pattern.
      Koilocytotic cells were observed in the stratum granulosum of the papillomatous
      lesions. Immunohistochemically, these abnormal cells were positive for PV group
      specific antigens. With transmission electron microscopy, virus particles were
      observed in crystalline intranuclear inclusions within keratinocytes. The
      presence of a mouse PV, designated MusPV, was confirmed by amplification of PV
      DNA with degenerative primers specific for PVs. This report is the first of a PV
      and its related disease in laboratory mice.

PMID- 20685916
TI  - Mannheimia haemolytica: bacterial-host interactions in bovine pneumonia.
AB  - Mannheimia haemolytica serotype S1 is considered the predominant cause of bovine
      pneumonic pasteurellosis, or shipping fever. Various virulence factors allow M
      haemolytica to colonize the lungs and establish infection. These virulence
      factors include leukotoxin (LKT), lipopolysaccharide, adhesins, capsule, outer
      membrane proteins, and various proteases. The effects of LKT are species specific
      for ruminants, which stem from its unique interaction with the bovine beta2
      integrin receptor present on leukocytes. At low concentration, LKT can activate
      bovine leukocytes to undergo respiratory burst and degranulation and stimulate
      cytokine release from macrophages and histamine release from mast cells. At
      higher concentration, LKT induces formation of transmembrane pores and subsequent
      oncotic cell necrosis. The interaction of LKT with leukocytes is followed by
      activation of these leukocytes to undergo oxidative burst and release
      proinflammatory cytokines such as interleukins 1, 6, and 8 and tumor necrosis
      factor alpha. Tumor necrosis factor alpha and other proinflammatory cytokines
      contribute to the accumulation of leukocytes in the lung. Formation of
      transmembrane pores and subsequent cytolysis of activated leukocytes possibly
      cause leakage of products of respiratory burst and other inflammatory mediators
      into the surrounding pulmonary parenchyma and so give rise to fibrinous and
      necrotizing lobar pneumonia. The effects of LKT are enhanced by
      lipopolysaccharide, which is associated with the release of proinflammatory
      cytokines from the leukocytes, activation of complement and coagulation cascade,
      and cell cytolysis. Similarly, adhesins, capsule, outer membrane proteins, and
      proteases assist in pulmonary colonization, evasion of immune response, and
      establishment of the infection. This review focuses on the roles of these
      virulence factors in the pathogenesis of shipping fever.

PMID- 20685917
TI  - Transferrin receptor expression in canine lymphoma.
AB  - Transferrin receptor 1 (TfR1) expression was measured by immunohistochemistry in
      78 archived cases of canine B-cell and T-cell lymphoma with an anti-human TfR1
      monoclonal antibody that was validated in the dog by immunohistochemistry and
      immunoblotting. The canine lymphoma cases were initially classified on the basis
      of World Health Organization criteria and then subdivided into the following 4
      subgroups: low-grade B-cell (LGB), high-grade B-cell (HGB), low-grade T-cell
      (LGT), and high-grade T-cell (HGT). A visual scoring system and densitometric
      analysis of the proportion and intensity of positive staining were used to
      quantify TfR1 expression. TfR1 expression was also correlated to mitotic rate.
      TfR1 expression was significantly lower in the LGT tumors compared to all other
      lymphoma subgroups (LGB, HGB, and HGT). LGB tumors showed a TfR1 expression
      similar to those of the high-grade tumors (HGB and HGT). Significant correlations
      were found between mitotic rate and densitometric TfR1 variables in the T-cell
      tumors but not in the B-cell tumors. Further studies are needed to investigate
      the underlying molecular basis of the high TfR1 expression in LGB lymphomas and
      its pathological relevance. The anti-human TfR1 monoclonal antibody is a useful
      tool for measurement of total cellular transferrin receptor expression in the
      dog; however, an antibody with specificity for the canine TfR1 ectodomain is
      needed to investigate the potential of this receptor as an oncolytic target.

PMID- 20685918
TI  - Clinicopathological characterization in poultry of three strains of Newcastle
      disease virus isolated from recent outbreaks.
AB  - Newcastle disease is a severe threat to the poultry industry and is caused by
      Newcastle disease virus, a member of the genus Avulavirus, family
      Paramyxoviridae. The virus is rapidly evolving, and several new genotypes have
      been discovered in the past few years. Characterization of these strains is
      important to evaluate field changes, anticipate new outbreaks, and develop
      adequate control measures. Three Newcastle disease isolates (APMV-1/duck/Vietnam,
      Long Bien/78/2002, APMV-1/chicken/Australia/9809-19-1107/1998, and APMV-1/double
      crested cormorant/USA, Nevada/19529-04/2005) from recent outbreaks were
      investigated via clinicopathological assessment, immunohistochemistry (IHC), in
      situ hybridization, virus isolation, and serology in experimentally infected 4
      week-old chickens. Phylogenetic studies showed that Australia isolate belongs to
      class II genotype I, Long Bien to class II genotype VIId, and Nevada cormorant to
      class II genotype V. Even though all 3 viruses had a virulent fusion protein
      cleavage site and ICPI values greater than 1.5, they all differed in their
      ability to cause clinical signs, in their lesions, and in their viral
      distribution in body tissues. The Long Bien isolate showed the most severe
      clinicopathological picture and the most widespread viral distribution. The
      Australia and Nevada cormorant isolates had a milder pathological phenotype, with
      viral replication restricted to only a few organs. The variability in
      clinicopathological characteristics despite the similarity in ICPI suggests that
      full clinicopathological assessment is necessary to fully characterize new
      isolates and that there are differences in pathogenesis among viruses of
      different genotypes.

PMID- 20685919
TI  - Commentary: mouse genetic nomenclature. Standardization of strain, gene, and
      protein symbols.
AB  - The use of standard nomenclatures for describing the strains, genes, and proteins
      of species is vital for the interpretation, archiving, analysis, and recovery of
      experimental data on the laboratory mouse. At a time when sharing of data and
      meta-analysis of experimental results is becoming a dominant mode of scientific
      investigation, failure to respect formal nomenclatures can cause confusion and
      errors and, in some cases, contribute to poor science. Here, the authors present
      the basic nomenclature rules for laboratory mice and explain how these rules
      should be applied to complex genetic manipulations and crosses.

PMID- 20685920
TI  - Optogenetic fMRI sheds light on the neural basis of the BOLD signal.
AB  - Blood oxygenation level dependent (BOLD) functional magnetic resonance imaging
      (fMRI) is widely used as a measure of neuronal activity, despite an incomplete
      understanding of the hemodynamic and neural bases for BOLD signals. Recent work
      by Lee and colleagues investigated whether activating genetically specified
      neurons elicits BOLD responses. Integrating optogenetic control of specific cells
      and fMRI showed that stimulating excitatory neurons triggers a positive BOLD
      signal with conventional kinetics locally and delayed weaker BOLD signals
      distally.

PMID- 20685921
TI  - Postsynaptic cell type-dependent cholinergic regulation of GABAergic synaptic
      transmission in rat insular cortex.
AB  - The cerebral cortex consists of multiple neuron subtypes whose
      electrophysiological properties exhibit diverse modulation patterns in response
      to neurotransmitters, including noradrenaline and acetylcholine (ACh). We
      performed multiple whole cell patch-clamp recording from layer V GABAergic
      interneurons and pyramidal cells of rat insular cortex (IC) to examine whether
      cholinergic effects on unitary inhibitory postsynaptic currents (uIPSCs) are
      differentially regulated by ACh receptors, depending on their presynaptic and
      postsynaptic cell subtypes. In fast-spiking (FS) to pyramidal cell synapses,
      carbachol (10 MUM) invariably decreased uIPSC amplitude by 51.0%, accompanied by
      increases in paired-pulse ratio (PPR) of the second to first uIPSC amplitude,
      coefficient of variation (CV) of the first uIPSC amplitude, and failure rate.
      Carbachol-induced uIPSC suppression was dose dependent and blocked by atropine, a
      muscarinic ACh receptor antagonist. Similar cholinergic suppression was observed
      in non-FS to pyramidal cell synapses. In contrast, FS to FS/non-FS cell synapses
      showed heterogeneous effects on uIPSC amplitude by carbachol. In roughly 40% of
      pairs, carbachol suppressed uIPSCs by 35.8%, whereas in a similar percentage of
      pairs uIPSCs were increased by 34.8%. Non-FS to FS/non-FS cell synapses also
      showed carbachol-induced uIPSC facilitation by 29.2% in about half of the pairs,
      whereas nearly 40% of pairs showed carbachol-induced suppression of uIPSCs by
      40.3%. Carbachol tended to increase uIPSC amplitude in interneuron-to-interneuron
      synapses with higher PPR, suggesting that carbachol facilitates GABA release in
      interneuron synapses with lower release probability. These results suggest that
      carbachol-induced effects on uIPSCs are not homogeneous but preiotropic: i.e.,
      cholinergic modulation of GABAergic synaptic transmission is differentially
      regulated depending on postsynaptic neuron subtypes.

PMID- 20685922
TI  - Regulation of AMPA receptor currents by mitochondrial ATP-sensitive K+ channels
      in anoxic turtle neurons.
AB  - Mammalian neurons rapidly undergo excitotoxic cell death during anoxia, whereas
      neurons from the anoxia-tolerant painted turtle survive without oxygen for hours
      and offer a unique model to study mechanisms to reduce the severity of cerebral
      stroke. An anoxia-mediated decrease in whole cell N-methyl-D-aspartate receptor
      and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)
      currents are an important part of the turtle's natural defense. Here we
      investigate the role of mitochondrial ATP-sensitive K(+) (mK(ATP)) channels in
      the regulation of AMPAR. Whole cell AMPAR currents were stable over 90 min of
      normoxic recording; however, anoxia resulted in a 52% decrease in AMPAR currents.
      Pharmacological activation of mK(ATP) channels with diazoxide or levcromakalim
      resulted in a 46% decrease in normoxic AMPAR currents and the decrease was
      abolished with application of the antagonists 5-hydroxydecanoic acid and
      glibenclamide, whereas mK(ATP) antagonists blocked the anoxia-mediated decrease.
      Mitochondrial K(Ca) channel modulators responded similarly. The Ca(2+)-uniporter
      antagonist ruthenium red reduced AMPAR currents by 38% and was blocked with the
      agonist spermine. The calcium chelator BAPTA in the recording electrode during
      anoxia or diazoxide perfusion also abolished the reduction in AMPAR currents. We
      conclude that the mK(ATP) channel is involved in the anoxia-mediated down
      regulation of AMPAR activity during anoxia and that it is a common mechanism to
      reduce glutamatergic excitability.

PMID- 20685923
TI  - Motor resonance may originate from sensorimotor experience.
AB  - In humans, the motor system can be activated by passive observation of actions or
      static pictures with implied action. The origin of this facilitation is of major
      interest to the field of motor control. Recently it has been shown that
      sensorimotor learning can reconfigure the motor system during action observation.
      Here we tested directly the hypothesis that motor resonance arises from
      sensorimotor contingencies by measuring corticospinal excitability in response to
      abstract non-action cues previously associated with an action. Motor evoked
      potentials were measured from the first dorsal interosseus (FDI) while human
      subjects observed colored stimuli that had been visually or motorically
      associated with a finger movement (index or little finger abduction).
      Corticospinal excitability was higher during the observation of a colored cue
      that preceded a movement involving the recorded muscle than during the
      observation of a different colored cue that preceded a movement involving a
      different muscle. Crucially this facilitation was only observed when the cue was
      associated with an executed movement but not when it was associated with an
      observed movement. Our findings provide solid evidence in support of the
      sensorimotor hypothesis of action observation and further suggest that the
      physical nature of the observed stimulus mediating this phenomenon may in fact be
      irrelevant.

PMID- 20685924
TI  - Age-related modifications of muscle synergies and spinal cord activity during
      locomotion.
AB  - Recent findings have shown that neural circuits located in the spinal cord drive
      muscular activations during locomotion while intermediating between descending
      signals and peripheral sensory information. This relationship could be modified
      by the natural aging process. To address this issue, the activity of 12
      ipsilateral leg muscles was analyzed in young and elderly people (7 subjects per
      group) while walking at six different cadences (40-140 steps/min). These signals
      were used to extract synergies underlying muscle activation and to map the
      motoneuronal activity of the pools belonging to the lumbosacral enlargement (L(2)
      S(2)). The comparison between the two groups showed that neither temporal
      patterning of motor primitives nor muscles loading synergies seemed to be
      significantly affected by aging. Conversely, as the cadence increased, spinal
      maps differ significantly between the groups, showing higher and scattered
      activity during the whole gait cycle in elders and well-defined bursts in young
      subjects. The results suggested that motor primitives lead the synchronization of
      muscle activation mainly depending on the biomechanical demand of the locomotion;
      hence they are not significantly affected by aging. Nevertheless, at the spinal
      cord level, biomechanical requirements, peripheral afference, and descending
      inputs are differently integrated between the two groups, probably reflecting age
      related changes of both nervous system and motor control strategies during
      locomotion.

PMID- 20685925
TI  - Linear and nonlinear contributions to the visual sensitivity of neurons in
      primate lateral geniculate nucleus.
AB  - Several parallel pathways convey retinal signals to the visual cortex of
      primates. The signals of the parvocellular (P) and magnocellular (M) pathways are
      well characterized; the properties of other rarely encountered cell types are
      distinctive in many ways, but it is not clear that they can provide signals with
      the same fidelity. Here we study this by characterizing the temporal receptive
      field of neurons in the lateral geniculate nucleus of anesthetized marmosets. For
      each neuron, we measured the response to a flickering uniform field, and, from
      this, estimated the linear and nonlinear receptive fields using spike-triggered
      average (STA) and spike-triggered covariance (STC) analyses. As expected the
      response of most P-cells was dominated by the STA, but the response of most M
      cells required additional nonlinear components, and these usually acted to
      suppress cell responses. The STC analysis showed stronger suppressive axes in
      suppressed-by-contrast cells, and both suppressive and excitatory axes in on-off
      cells. Together, the STA and the STC analyses form a model of the temporal
      response to a large uniform field: under this model, the information that was
      provided by suppressed-by-contrast cells or on-off cells approached that provided
      by the P- and M-cells. However, whereas P- and M-cells provided more information
      about luminance, the nonlinear cells provided more information about the contrast
      energy. This suggests that the nonlinear cells provide complimentary signals to
      those of P- and M-cells, with reasonably high fidelity, and may play an important
      role in normal visual processing.

PMID- 20685926
TI  - On the origin of the extracellular field potential in the nucleus laminaris of
      the barn owl (Tyto alba).
AB  - The neurophonic is a sound-evoked, frequency-following potential that can be
      recorded extracellularly in nucleus laminaris of the barn owl. The origin of the
      neurophonic, and thus the mechanisms that give rise to its exceptional temporal
      precision, has not yet been identified. Putative generators of the neurophonic
      are the activity of afferent axons, synaptic activation of laminaris neurons, or
      action potentials in laminaris neurons. To identify the generators, we analyzed
      the neurophonic in the high-frequency (>2.5 kHz) region of nucleus laminaris in
      response to monaural pure-tone stimulation. The amplitude of the neurophonic is
      typically in the millivolt range. The signal-to-noise ratio reaches values beyond
      30 dB. To assess which generators could give rise to these large, synchronous
      extracellular potentials, we developed a computational model. Spike trains were
      produced by an inhomogeneous Poisson process and convolved with a spike waveform.
      The model explained the dependence of the simulated neurophonic on parameters
      such as the mean rate, the vector strength of phase locking, the number of
      statistically independent sources, and why the signal-to-noise ratio is
      independent of the spike waveform and subsequent filtering of the signal. We
      found that several hundred sources are needed to reach the observed signal-to
      noise ratio. The summed coherent signal from the densely packed afferent axons
      and activation of their synapses on laminaris neurons are alone sufficient to
      explain the measured properties of the neurophonic.

PMID- 20685928
TI  - Coding of stimuli by ampullary afferents in Gnathonemus petersii.
AB  - Weakly electric fish use electroreception for both active and passive
      electrolocation and for electrocommunication. While both active and passive
      electrolocation systems are prominent in weakly electric Mormyriform fishes,
      knowledge of their passive electrolocation ability is still scarce. To better
      estimate the contribution of passive electric sensing to the orientation toward
      electric stimuli in weakly electric fishes, we investigated frequency tuning
      applying classical input-output characterization and stimulus reconstruction
      methods to reveal the encoding capabilities of ampullary receptor afferents.
      Ampullary receptor afferents were most sensitive (threshold: 40 MUV/cm) at low
      frequencies (<10 Hz) and appear to be tuned to a mix of amplitude and slope of
      the input signals. The low-frequency tuning was corroborated by behavioral
      experiments, but behavioral thresholds were one order of magnitude higher. The
      integration of simultaneously recorded afferents of similar frequency-tuning
      resulted in strongly enhanced signal-to-noise ratios and increased mutual
      information rates but did not increase the range of frequencies detectable by the
      system. Theoretically the neuronal integration of input from receptors
      experiencing opposite polarities of a stimulus (left and right side of the fish)
      was shown to enhance encoding of such stimuli, including an increase of
      bandwidth. Covariance and coherence analysis showed that spiking of ampullary
      afferents is sufficiently explained by the spike-triggered average, i.e.,
      receptors respond to a single linear feature of the stimulus. Our data support
      the notion of a division of labor of the active and passive electrosensory
      systems in weakly electric fishes based on frequency tuning. Future experiments
      will address the role of central convergence of ampullary input that we expect to
      lead to higher sensitivity and encoding power of the system.

PMID- 20685927
TI  - Context-dependent partitioning of motor learning in bimanual movements.
AB  - Human subjects easily adapt to single dynamic or visuomotor perturbations. In
      contrast, when two opposing dynamic or visuomotor perturbations are presented
      sequentially, interference is often observed. We examined the effect of bimanual
      movement context on interference between opposing perturbations using pairs of
      contexts, in which the relative direction of movement between the two arms was
      different across the pair. When each perturbation direction was associated with a
      different bimanual context, such as movement of the arms in the same direction
      versus movement in the opposite direction, interference was dramatically reduced.
      This occurred over a short period of training and was seen for both dynamic and
      visuomotor perturbations, suggesting a partitioning of motor learning for the
      different bimanual contexts. Further support for this was found in a series of
      transfer experiments. Having learned a single dynamic or visuomotor perturbation
      in one bimanual context, subjects showed incomplete transfer of this learning
      when the context changed, even though the perturbation remained the same. In
      addition, we examined a bimanual context in which one arm was moved passively and
      show that the reduction in interference requires active movement. The sensory
      consequences of movement are thus insufficient to allow opposing perturbations to
      be co-represented. Our results suggest different bimanual movement contexts
      engage at least partially separate representations of dynamics and kinematics in
      the motor system.

PMID- 20685929
TI  - Multiple Ca2+-dependent mechanisms regulate L-type Ca2+ current in retinal
      amacrine cells.
AB  - Understanding the regulation of L-type voltage-gated Ca(2+) current is an
      important component of elucidating the signaling capabilities of retinal amacrine
      cells. Here we ask how the cytosolic Ca(2+) environment and the balance of Ca(2+)
      dependent effectors shape native L-type Ca(2+) channel function in these cells.
      To achieve this, whole cell voltage clamp recordings were made from cultured
      amacrine cells under conditions that address the contribution of mitochondrial
      Ca(2+) uptake (MCU), Ca(2+)/calmodulin (CaM)-dependent channel inactivation
      (CDI), protein kinase A (PKA), and Ca(2+)-induced Ca(2+) release (CICR). Under
      control conditions, repeated activation of the L-type channels produces a
      progressive enhancement of the current. Inhibition of MCU causes a reduction in
      the Ca(2+) current amplitude that is dependent on Ca(2+) influx as well as
      cytosolic Ca(2+) buffering, consistent with CDI. Including the Ca(2+) buffer bis
      (o-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA) internally can shift the
      balance between enhancement and inhibition such that inhibition of MCU can
      enhance the current. Inhibition of PKA can remove the enhancing effect of BAPTA
      suggesting that cyclic AMP-dependent phosphorylation is involved. Inhibition of
      CaM suppresses CDI but spares the enhancement, consistent with the substantially
      higher sensitivity of the Ca(2+)-sensitive adenylate cyclase 1 (AC1) to
      Ca(2+)/CaM. Inhibition of the ryanodine receptor reduces the current amplitude,
      suggesting that CICR might normally amplify the activation of AC1 and stimulation
      of PKA activity. These experiments reveal that the amplitude of L-type Ca(2+)
      currents in retinal amacrine cells are both positively and negatively regulated
      by Ca(2+)-dependent mechanisms.

PMID- 20685930
TI  - Distinct AMPA-type glutamatergic synapses in developing rat CA1 hippocampus.
AB  - We assessed synaptic alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate
      receptor (AMPAR) properties during synaptogenesis to describe the development of
      individual glutamatergic synapses on rat hippocampal CA1 principal neurons.
      Pharmacologically isolated AMPAR-mediated glutamatergic synaptic currents [evoked
      by stimulation of the Schaffer Collateral pathway, excitatory postsynaptic
      currents (EPSCs)], had significantly greater inward-rectification at ages P5-7
      compared with P8-18. These inward rectifying EPSCs demonstrated paired-pulse
      dependent unblocking at positive holding potentials, consistent with voltage
      dependent internal polyamine block. Measurements of paired-pulse facilitation did
      not support altered presynaptic properties associated with inward rectification.
      Using asynchronous EPSCs (aEPSCs) to analyze populations of individual synapses,
      we found that quantal amplitudes (Q) increased across early postnatal development
      (P5-P18) and were directly modulated by increases in the number of activated
      receptors. Quantal AMPAR decay kinetics (aEPSC tau(decay)s) exhibited the highest
      coefficient of variation (CV) from P5 to 7 and became markedly less variable at
      P8-18. At P5-7, faster quantal kinetics coexisted with much slower kinetics; only
      slower quantal kinetics were found at P8-18. This supports diverse quantal
      synaptic properties limited to P5-7. Multivariate cluster analysis of Q, CV(tau
      decay), and median tau(decay) supported a segregation of neurons into two
      distinct age groups of P5-7 and P8-18, similar to the age-related segregation
      suggested by inward rectification. Taken together, these findings support
      synaptic, calcium permeable AMPARs at a subset of synapses onto CA1 pyramidal
      neurons exclusively at P5-7. These distinct synapses coexist with those sharing
      the properties of more mature synapses. These synapses disappear after P7 as
      activated receptor numbers increase with age.

PMID- 20685931
TI  - N-(3-Cyanophenyl)-2-phenylacetamide, an effective inhibitor of morbillivirus
      induced membrane fusion with low cytotoxicity.
AB  - Based on the structural similarity of viral fusion proteins within the family
      Paramyxoviridae, we tested recently described and newly synthesized acetanilide
      derivatives for their capacity to inhibit measles virus (MV)-, canine distemper
      virus (CDV)- and Nipah virus (NiV)-induced membrane fusion. We found that N-(3
      cyanophenyl)-2-phenylacetamide (compound 1) has a high capacity to inhibit MV-
      and CDV-induced (IC(50) MUM), but not NiV-induced, membrane fusion. This compound
      is of outstanding interest because it can be easily synthesized and its
      cytotoxicity is low [50 % cytotoxic concentration (CC(50)) >= 300 MUM], leading
      to a CC(50)/IC(50) ratio of approximately 100. In addition, primary human
      peripheral blood lymphocytes and primary dog brain cell cultures (DBC) also
      tolerate high concentrations of compound 1. Infection of human PBMC with
      recombinant wild-type MV is inhibited by an IC(50) of approximately 20 MUM. The
      cell-to-cell spread of recombinant wild-type CDV in persistently infected DBC can
      be nearly completely inhibited by compound 1 at 50 MUM, indicating that the virus
      spread between brain cells is dependent on the activity of the viral fusion
      protein. Our findings demonstrate that this compound is a most applicable
      inhibitor of morbillivirus-induced membrane fusion in tissue culture experiments
      including highly sensitive primary cells.

PMID- 20685932
TI  - Increases in IgA(+) B cells in Peyer's patches during milk-borne mouse mammary
      tumor virus infection are influenced by Toll-like receptor 4 and are completely
      dependent on the superantigen response.
AB  - Mouse mammary tumor virus (MMTV) is a milk-borne betaretrovirus that has
      developed strategies to exploit and subvert the host immune system. Although
      mammary glands are the final target of infection, Peyer's patches (PP) are the
      entry site of the virus. Herein, we show that the infection induces increases in
      the number of PP IgA(+) B cells and higher expression of the alpha circular
      transcript, which is a specific marker of the switch to IgA. In addition, IgA(+)
      B-cell increases correlated with higher levels of cytokines related to IgA class
      switching, such as interleukin (IL)-5 and IL-6. Of interest, the increases in
      IgA(+) B cells were lower in Toll-like receptor 4-deficient mice and were
      completely dependent on the presence of superantigen-reactive T cells. Our
      results point to a novel mechanism involved in MMTV infection and suggest that
      IgA(+) B cells may play an important role in carrying the virus to the mammary
      glands.

PMID- 20685933
TI  - Neutralization activity in a geographically diverse East London cohort of human
      immunodeficiency virus type 1-infected patients: clade C infection results in a
      stronger and broader humoral immune response than clade B infection.
AB  - The array of human immunodeficiency virus (HIV) subtypes encountered in East
      London, an area long associated with migration, is unusually heterogeneous,
      reflecting the diverse geographical origins of the population. In this study it
      was shown that viral subtypes or clades infecting a sample of HIV type 1 (HIV-1)
      positive individuals in East London reflect the global pandemic. The authors
      studied the humoral response in 210 treatment-naive chronically HIV-1-infected
      (>1 year) adult subjects against a panel of 12 viruses from six different clades.
      Plasmas from individuals infected with clade C, but also plasmas from clade A,
      and to a lesser degree clade CRF02_AG and CRF01_AE, were significantly more
      potent at neutralizing the tested viruses compared with plasmas from individuals
      infected with clade B. The difference in humoral robustness between clade C- and
      B-infected patients was confirmed in titration studies with an extended panel of
      clade B and C viruses. These results support the approach to develop an HIV-1
      vaccine that includes clade C or A envelope protein (Env) immunogens for the
      induction of a potent neutralizing humoral response.

PMID- 20685934
TI  - Construction and immunogenicity of recombinant adenovirus vaccines expressing the
      HMW1, HMW2, or Hia adhesion protein of nontypeable Haemophilus influenzae.
AB  - The objective of the present study was to construct and assess the immunogenicity
      of recombinant adenovirus vectors expressing the HMW1, HMW2, or Hia protein of
      nontypeable Haemophilus influenzae (NTHi). These proteins are critical adhesins
      and potential protective antigens expressed by NTHi. Segments of the hmw1A and
      hmw2A structural genes that encode the distal one-half of mature HMW1 or HMW2
      were cloned into the T7 expression vector pGEMEX-2. These constructs encoded
      stable HMW1 or HMW2 recombinant fusion protein that expresses B-cell epitopes
      common to most NTHi strains. A segment of the hia gene that encodes the surface
      exposed portion of mature Hia was also cloned into pGEMEX-2. The resulting T7
      gene 10 translational fusions were excised from the parent plasmids and cloned
      into the shuttle plasmid pDC316. Cotransfection of HEK 293 cells with the pDC316
      derivatives and pBHGloxDeltaE1,3Cre resulted in the production of viral plaques
      from which recombinant adenoviruses expressing fusion proteins were recovered.
      Chinchillas immunized intraperitoneally with a single 10(8)-PFU dose of either
      the HMW2 or Hia adenoviral construct developed high anti-HMW2 or anti-Hia serum
      antibody titers within 4 weeks of immunization. Chinchillas immunized
      intranasally with a single 10(7)- to 10(9)-PFU dose of the Hia adenoviral
      construct also developed high anti-Hia serum antibody titers within 8 weeks of
      immunization. Recombinant adenoviruses represent a promising system to induce
      mucosal and systemic immunity and protection against mucosal diseases such as
      otitis media. Recombinant adenoviruses expressing recombinant HMW1, HMW2, or Hia
      protein will be important new tools in NTHi vaccine development efforts.

PMID- 20685935
TI  - Influence of advanced age on Mycobacterium bovis BCG vaccination in guinea pigs
      aerogenically infected with Mycobacterium tuberculosis.
AB  - Mycobacterium bovis bacillus Calmette-Guerin (BCG) is the only tuberculosis (TB)
      vaccine currently available, but its efficacy against adult pulmonary TB remains
      controversial. BCG induces specific immune responses to mycobacterial antigens
      and may elicit protective immunity against TB. TB remains a major public health
      problem, especially among the elderly, yet the efficacy of BCG in the elderly is
      unknown. We investigated the ability of BCG vaccination to prevent TB in young (6
      week-old), middle-aged (18-month-old), and old (60-month-old) guinea pigs. BCG
      Tokyo vaccination reduced the growth of Mycobacterium tuberculosis H37Rv in all
      three groups. By use of an enzyme-linked immunospot (ELISPOT) assay, antigen
      specific gamma interferon (IFN-gamma)-producing cells were detected in the 60
      month-old guinea pigs after a booster vaccination with BCG-Tokyo. Our findings
      suggest that BCG-Tokyo has a protective effect against tuberculosis infection
      regardless of age.

PMID- 20685936
TI  - Occupational asthma induced by Chrysonilia sitophila in a worker exposed to
      coffee grounds.
AB  - A new case of occupational asthma caused by Chrysonilia sitophila (asexual state
      of Neurospora sitophila) was diagnosed by molecular identification of the mold
      and confirmed by skin prick test, peak expiratory flow rate measurements, and
      experimental immunoglobulin E analysis.

PMID- 20685937
TI  - Enterovirus 71 infection of monocytes with antibody-dependent enhancement.
AB  - Enterovirus (EV) is an RNA virus that has circulated with different serotypes and
      genotypes worldwide. Enterovirus 71 (EV71) is a major neurotropic virus that
      causes severe brain stem encephalitis (BE) in infants and young children. The
      most vulnerable age for fatal infection is 6 to 11 months. This is associated
      with the coincident decline in maternal antibodies. The current report describes
      our finding that EV71 can infect human peripheral blood monocytes. We were able
      to show that EV71 infection is enhanced in the monocytic cell line THP-1 by the
      presence of subneutralizing concentrations of anti-EV71 antibodies. We also found
      that antibody-dependent enhancement (ADE) is mediated in part by Fcgamma
      receptors. These observations support the concept that ADE augments the
      infectivity of EV71 for human monocytes and contributes to the age-dependent
      pathogenesis of EV71-induced disease. The ADE phenomenon must be considered
      during the development of an EV71 vaccine.

PMID- 20685938
TI  - False-positive rate of a "fourth-generation" HIV antigen/antibody combination
      assay in an area of low HIV prevalence.
AB  - We retrospectively analyzed the performance of the Architect HIV antigen/antibody
      (Ag/Ab) combination assay in a tertiary health care center with a situation of
      low HIV prevalence. The specificity and positive predictive value (PPV) were
      99.78% and 31.21%, respectively. However, the specificity and PPV could increase
      to 99.99% and 89.70% using an arbitrary cutoff value.

PMID- 20685939
TI  - CREB is a positive transcriptional regulator of gamma interferon in latent but
      not active tuberculosis infections.
AB  - Gamma interferon (IFN-gamma) is a crucial cytokine for protection against
      Mycobacterium tuberculosis, but the mechanism of IFN-gamma transcription is still
      unclear. The cyclic AMP (cAMP) responsive element binding (CREB) proteins belong
      to the bZip (basic leucine zipper) family of transcription factors and are
      essential for T-cell function and cytokine production. This study focused on the
      capacity of CREB proteins to regulate IFN-gamma transcription in CD3(+) T cells
      obtained from tuberculosis (TB) patients and persons with latent tuberculosis
      infection (LTBI) in China. The electrophoretic mobility shift assay (EMSA),
      chromatin immunoprecipitation (ChIP), and Western blotting were used to
      demonstrate the regulatory role of CREB. EMSA (in vitro) and ChIP (in vivo)
      experiments suggested CREB could bind to the IFN-gamma proximal promoter in
      persons with LTBI, whereas no binding was detected in TB patients. Western
      blotting confirmed the expression of CREB proteins, especially serine-133
      phosphorylated CREB, was markedly reduced in TB patients compared with persons
      with LTBI. These results suggested that CREB could promote the transcription and
      production of IFN-gamma through binding with the IFN-gamma proximal promoter, but
      the regulatory role of CREB was decreased in tuberculosis patients owing to
      diminished expression of CREB proteins, which in turn reduced the IFN-gamma
      production.

PMID- 20685940
TI  - Unique Th1/Th2 phenotypes induced during priming and memory phases by use of
      interleukin-12 (IL-12) or IL-28B vaccine adjuvants in rhesus macaques.
AB  - Adjuvant compounds are usually included in vaccinations in order to bolster total
      vaccine-specific responses or to tailor an immune response toward a desired
      endpoint, such as the production of gamma interferon or an increase in antibody
      titers. While most adjuvants are studied in regard to their impact on vaccine
      specific responses during and just after the vaccination period, a detailed
      analysis of how adjuvants skew the Th1/Th2 axis at more distant time points is
      not often undertaken. In the current study, we present data that suggests that
      adjuvants differ in their relative abilities to bolster and skew immune responses
      in the short term compared with more distant time points. To that end, we have
      employed interleukin-12 (IL-12) and IL-28B as adjuvants for DNA vaccination of
      rhesus macaques. While both adjuvants were able to bolster Th1-biased responses,
      our analysis shows that this skewing was achieved through different mechanisms.
      Moreover, analysis 3 months after the final immunization revealed the activity of
      the IL-12 adjuvant to be short lived, while the IL-28B adjuvant continued to
      exert its influence on the immune system. Taken together, these data suggest that
      the scientific and medical communities would benefit from a more detailed
      analysis of adjuvant function, including the determination of long-term
      influences of administered adjuvants.

PMID- 20685941
TI  - Not just the powerhouse of the cell: emerging roles for mitochondria in the
      heart.

PMID- 20685942
TI  - Mitochondrial SIRT3 and heart disease.
AB  - Sirtuins are emerging as key regulators of many cellular functions including
      metabolism, cell growth, apoptosis, and genetic control of ageing. In mammals
      there are seven sirtuin analogues, SIRT1 to SIRT7. Among them SIRT3 is unique
      because this is the only analogue whose increased expression has been found to be
      associated with extended lifespan of humans. SIRT3 levels have been shown to be
      elevated by exercise and calorie restriction. Although the role of SIRT3 in cell
      biology is only beginning to be understood, initial studies have shown that SIRT3
      plays a major role in free fatty acid oxidation and maintenance of cellular ATP
      levels. In the heart SIRT3 has been found to block development of cardiac
      hypertrophy and protect cardiomyocytes from oxidative stress-mediated cell death.
      Similarly, SIRT3 has been reported to have tumour-suppressive characteristics. In
      this article, we review the known effects of SIRT3 in different tissues and
      relate them to the protection of cardiomyocytes under stress.

PMID- 20685943
TI  - Non-invasive characterization of the area-at-risk using magnetic resonance
      imaging in chronic ischaemia.
AB  - AIMS: we investigated the performance of quantitative stress perfusion magnetic
      resonance imaging (MRI) as a basis for identifying and characterizing the area-at
      risk subtending a chronic coronary artery (CA) stenosis. METHODS AND RESULTS:
      pigs underwent a percutaneous copper-coated stent implantation in the circumflex
      CA (n = 11) or a sham operation (n = 5). After 6 weeks, angiography and MRI were
      performed including cine (rest, low- and high-dose dobutamine stress), dual-bolus
      first-pass perfusion (rest and adenosine stress), and contrast-enhanced imaging
      to quantify myocardial infarction (MI). Myocardial blood flow (MBF) was
      quantified based on Fermi-model deconvolution and compared with microsphere
      measurements. On the basis of Evan's blue staining, MBF thresholds to define the
      area-at-risk were determined by receiver-operating characteristic (ROC) analysis.
      CA stenosis was 94 +/- 7% and infarct size (IS) 7.3 +/- 3.1% of left ventricular
      mass. Segmental thresholds of hyperaemic MBF yielded the best performance for
      detecting area-at-risk. There was a good correlation between MRI and microsphere
      perfusion (r(2) = 0.84, P < .0001). The area-at-risk presented a mixed substrate
      of non-infarcted (non-MI), <50% infarcted (MI+), and >50% infarcted (MI++)
      segments. MBF was reduced in at-risk vs. remote segments at rest (non-MI, 0.50 +/
      0.21; MI+, 0.47 +/- 0.14; MI++, 0.42 +/- 0.14; remote, 0.84 +/- 0.25 mL/min/g)
      and during stress (non-MI, 0.69 +/- 0.09; MI+, 0.66 +/- 0.14; MI++, 0.51 +/-
      0.11; remote, 1.70 +/- 0.36 mL/min/g). Segmental wall thickening showed different
      responses to stress (remote, progressive increase during incremental stress; non
      MI, increase at low-dose and discontinued at high-dose; MI+, initial increase and
      decrease at high-dose; MI++, progressive decrease). CONCLUSION: quantitative
      hyperaemic perfusion MRI accurately defines segments in the area-at-risk in
      chronic ischaemia, which present with different functional response to stress
      related to segmental IS.

PMID- 20685944
TI  - Calcium absorption revisited.

PMID- 20685945
TI  - Carbohydrate quantity and quality and risk of type 2 diabetes in the European
      Prospective Investigation into Cancer and Nutrition-Netherlands (EPIC-NL) study.
AB  - BACKGROUND: Carbohydrate quantity and quality may play an important role in the
      development of type 2 diabetes. OBJECTIVE: We investigated the associations of
      dietary glycemic load (GL), glycemic index (GI), carbohydrate, and fiber intake
      with the incidence of type 2 diabetes. DESIGN: A prospective cohort study was
      conducted in 37,846 participants of the EPIC-NL (European Prospective
      Investigation into Cancer and Nutrition-Netherlands) study, aged 21-70 y at
      baseline and free of diabetes. Dietary intake was assessed with the use of a
      validated food-frequency questionnaire. Incident diabetes cases were mainly self
      reported and verified against general practitioner records. RESULTS: During a
      mean follow-up of 10 y, 915 incident diabetes cases were documented. Dietary GL
      was associated with an increased diabetes risk after adjustment for age, sex,
      established diabetes risk factors, and dietary factors [hazard ratio (HR) per SD
      increase: 1.27; 95% CI: 1.11, 1.44; P < 0.001] [corrected]. GI tended to increase
      diabetes risk (HR: 1.08; 95% CI: 1.00, 1.17; P = 0.05). Dietary fiber was
      inversely associated with diabetes risk (HR: 0.92; 95% CI: 0.85, 0.99; P < 0.05),
      whereas carbohydrate intake was associated with increased diabetes risk (HR:
      1.15; 95% CI: 1.01, 1.32; P < 0.05). Of the carbohydrate subtypes, only starch
      was related to increased diabetes risk [HR: 1.25 (1.07, 1.46), P < 0.05]. All
      associations became slightly stronger after exclusion of energy misreporters.
      CONCLUSIONS: Diets high in GL, GI, and starch and low in fiber were associated
      with an increased diabetes risk. Both carbohydrate quantity and quality seem to
      be important factors in diabetes prevention. Energy misreporting contributed to a
      slight attenuation of associations.

PMID- 20685946
TI  - Effect of long-chain polyunsaturated fatty acid supplementation during pregnancy
      or lactation on infant and child body composition: a systematic review.
AB  - BACKGROUND: n-3 (omega-3) Long-chain polyunsaturated fatty acids (LC-PUFAs)
      inhibit fat cell differentiation and fat storage in adults, and this has led to
      the hypothesis that maternal n-3 LC-PUFA supplementation may reduce fat mass in
      children. OBJECTIVE: The objective of this systematic review was to evaluate the
      effect of n-3 LC-PUFA supplementation in pregnancy or lactation on infant and
      child body composition in randomized controlled trials. DESIGN: MEDLINE and
      EMBASE databases were searched for relevant articles. Human trials that
      supplemented the maternal diet with n-3 LC-PUFAs during pregnancy or lactation
      and assessed either body fat mass or body mass index in children were included.
      Trials had to be randomized in design. The quality of all included studies was
      assessed against set criteria, and results of eligible trials were compared.
      RESULTS: There were only 3 human trials (4 publications) that met our inclusion
      criteria. There was considerable disparity in study design and trial quality. The
      results were variable and showed positive, negative, or neutral effects of
      maternal n-3 LC-PUFA supplementation on body fat mass in children. CONCLUSIONS:
      This systematic review highlights the paucity of robust data from human studies
      to evaluate the effect of increased n-3 LC-PUFA exposure during the perinatal
      period on body fat mass in offspring. Further studies are required in which the
      intervention is confined to the perinatal period and that are sufficiently
      powered, have appropriate controls, have adequate blinding of participants and
      investigators, and have high retention rates.

PMID- 20685948
TI  - Vitamin K and cystic fibrosis: give me a double, please.

PMID- 20685947
TI  - Diet quality and weight gain among black and white young adults: the Coronary
      Artery Risk Development in Young Adults (CARDIA) Study (1985-2005).
AB  - BACKGROUND: Little is known about the long-term health consequences of following
      the 2005 Dietary Guidelines for Americans (DGA; Washington, DC: US Government
      Printing Office, 2005). OBJECTIVE: The objective was to examine the longitudinal
      association between diets consistent with the 2005 DGA and subsequent weight
      gain. DESIGN: We used data from the Coronary Artery Risk Development in Young
      Adults (CARDIA) Study, a cohort of black and white men and women aged 18-30 y at
      baseline who attended <=7 examinations from 1985-1986 to 2005-2006 (n = 4913). We
      created a 100-point Diet Quality Index (2005 DQI) to rate participants' diets
      based on meeting the 2005 DGA key recommendations. Longitudinal models of weight
      gain were adjusted for physical activity, smoking, energy intake, age, education,
      sex, and initial body mass index (BMI) and included interaction terms of DQI by
      race and initial BMI (if statistically significant). RESULTS: We found effect
      modification by race (likelihood ratio test, P < 0.03 in all models). The mean
      adjusted 20-y weight change was +19.4 kg for blacks and +11.2 kg for whites with
      high diet quality (DQI >70) and +17.8 for blacks and +13.9 for whites with a DQI
      <50 (P < 0.05). In race-specific Cox models (with interaction terms for DQI *
      initial BMI, P < 0.05), a 10-point increase in DQI score was associated with a
      10% lower risk of gaining 10 kg in whites with an initial BMI (in kg/m(2)) <25
      but with a 15% higher risk in blacks with baseline obesity (P < 0.001).
      CONCLUSIONS: Our findings do not support the hypothesis that a diet consistent
      with the 2005 DGA benefits long-term weight maintenance in American young adults.
      Greater need for attention to obesity prevention in future DGAs is warranted.

PMID- 20685949
TI  - Contributors of water intake in US children and adolescents: associations with
      dietary and meal characteristics--National Health and Nutrition Examination
      Survey 2005-2006.
AB  - BACKGROUND: Little is known about the association of contributors of total water
      intake with dietary characteristics in US children. OBJECTIVE: We examined
      intakes of total water and its contributors and their associations with diet and
      meal reporting in children and adolescents. DESIGN: Dietary data for children 2
      19 y of age (n = 3978) from the National Health and Nutrition Examination Survey
      2005-2006 were used to compute usual intake of total water. The association of
      total water and its contributors with sociodemographic characteristics and
      dietary and meal attributes was examined by using multiple regression analysis.
      RESULTS: The adjusted mean intakes of total water in Americans aged 2-5, 6-11,
      and 12-19 y were 1.4, 1.6, and 2.4 L, respectively. The mean usual intake of
      total water was generally less than the Adequate Intake; overall, more boys
      reported intakes of at least the Adequate Intake. The percentage of total water
      intake from plain water increased with age. Plain water intake was inversely
      associated with the intake of beverage moisture and the energy density of foods;
      conversely, beverage moisture was positively associated with dietary energy, fat,
      and the energy density of foods. Associations of water contributors with meal
      patterns (number of eating occasions, reporting of breakfast or snack) were
      inconsistent across age groups. Nearly 80% of food moisture, >66% of beverage
      moisture, and ~30% of plain water were reported with main meals. CONCLUSIONS:
      Intake of total water over 24 h from different contributors varied by age.
      Qualitative differences in dietary intake in association with the amount of plain
      water and beverage moisture in the recalls were observed. American children and
      adolescents consumed more than two-thirds of their daily beverages with main
      meals.

PMID- 20685950
TI  - Dietary intake of saturated fatty acids and mortality from cardiovascular disease
      in Japanese: the Japan Collaborative Cohort Study for Evaluation of Cancer Risk
      (JACC) Study.
AB  - BACKGROUND: Prospective epidemiologic studies have generated mixed results
      regarding the association between saturated fatty acid (SFA) intake and risk of
      ischemic heart disease (IHD) and stroke. These associations have not been
      extensively studied in Asians. OBJECTIVE: The aim of this study was to test the
      hypothesis that SFA intake is associated with the risk of cardiovascular disease
      mortality in Japanese whose average SFA intake is low. DESIGN: The Japan
      Collaborative Cohort Study for Evaluation of Cancer Risk (JACC Study) comprised
      58,453 Japanese men and women who completed a food-frequency questionnaire.
      Participants were aged 40-79 y at baseline (1988-1990) and were followed up for
      14.1 y. Associations of energy-adjusted SFA intake with mortality from stroke
      (intraparenchymal and subarachnoid hemorrhages and ischemic stroke) and heart
      diseases (IHD, cardiac arrest, and heart failure) were examined after adjustment
      for age, sex, and cardiovascular disease risk and dietary factors. RESULTS: We
      observed inverse associations of SFA intake with mortality from total stroke [n =
      976; multivariable hazard ratio (95% CI) for highest compared with lowest
      quintiles: 0.69 (0.53, 0.89); P for trend = 0.004], intraparenchymal hemorrhage
      [n = 224; 0.48 (0.27, 0.85); P for trend = 0.03], and ischemic stroke [n = 321;
      0.58 (0.37, 0.90); P for trend = 0.01]. No multivariable-adjusted associations
      were observed between SFA and mortality from subarachnoid hemorrhage [n = 153;
      0.91 (0.46, 1.80); P for trend = 0.47] and heart disease [n = 836; 0.89 (0.68,
      1.15); P for trend = 0.59]. CONCLUSION: SFA intake was inversely associated with
      mortality from total stroke, including intraparenchymal hemorrhage and ischemic
      stroke subtypes, in this Japanese cohort.

PMID- 20685951
TI  - Effect of increased consumption of whole-grain foods on blood pressure and other
      cardiovascular risk markers in healthy middle-aged persons: a randomized
      controlled trial.
AB  - BACKGROUND: Three daily portions of whole-grain foods could lower cardiovascular
      disease risk, but a comprehensive intervention trial was needed to confirm this
      recommendation. OBJECTIVES: We aimed to assess the effects of consumption of 3
      daily portions of whole-grain foods (provided as only wheat or a mixture of wheat
      and oats) on markers of cardiovascular disease risk in relatively high-risk
      individuals. DESIGN: This was a randomized controlled dietary trial in middle
      aged healthy individuals. After a 4-wk run-in period with a refined diet, we
      randomly allocated volunteers to a control (refined diet), wheat, or wheat + oats
      group for 12 wk. The primary outcome was a reduction of cardiovascular disease
      risk factors by dietary intervention with whole grains, which included lipid and
      inflammatory marker concentrations, insulin sensitivity, and blood pressure.
      RESULTS: We recruited a total of 233 volunteers; 24 volunteers withdrew, and 3
      volunteers were excluded. Systolic blood pressure and pulse pressure were
      significantly reduced by 6 and 3 mm Hg, respectively, in the whole-grain foods
      groups compared with the control group. Systemic markers of cardiovascular
      disease risk remained unchanged apart from cholesterol concentrations, which
      decreased slightly but significantly in the refined group. CONCLUSIONS: Daily
      consumption of 3 portions of whole-grain foods can significantly reduce
      cardiovascular disease risk in middle-aged people mainly through blood pressure
      lowering mechanisms. The observed decrease in systolic blood pressure could
      decrease the incidence of coronary artery disease and stroke by >=15% and 25%,
      respectively. This trial was registered at clinicaltrials.gov as ISRCTN27657880.

PMID- 20685952
TI  - The effect of zinc on pneumonia in children: is it really ineffective?

PMID- 20685954
TI  - An ileal brake-through?

PMID- 20685953
TI  - Noninvasive assessment of dermal carotenoids as a biomarker of fruit and
      vegetable intake.
AB  - BACKGROUND: Resonance Raman spectroscopy (RRS) has been suggested as a feasible
      method for noninvasive carotenoid measurement of human skin. However, before RRS
      measures of dermal carotenoids can be used as a biomarker, data on intra- and
      intersubject variability and validity are needed. OBJECTIVE: The purpose of this
      study was to evaluate the reproducibility and validity of RRS measures of dermal
      total carotenoids and lycopene in humans. DESIGN: In study 1, 74 men and women
      with diverse skin pigmentation were recruited. RRS measures of the palm, inner
      arm, and outer arm were obtained at baseline, 1 wk, 2 wk, 1 mo, 3 mo, and 6 mo
      (to maximize seasonal variation). The RRS device used visible light at 488 nm to
      estimate total carotenoids and at 514 nm to estimate lycopene. Reproducibility
      was assessed by intraclass correlation coefficients (ICCs). In study 2, we
      recruited 28 subjects and assessed dietary carotenoid intake, obtained blood for
      HPLC analyses, performed RRS measures of dermal carotenoid status, and performed
      dermal biopsies (3-mm punch biopsy) with dermal carotenoids assessed by HPLC.
      RESULTS: ICCs for total carotenoids across time were 0.97 (palm), 0.95 (inner
      arm), and 0.93 (outer arm). Total dermal carotenoids assessed by RRS were
      significantly correlated with total dermal carotenoids assessed by HPLC of dermal
      biopsies (r = 0.66, P = 0.0001). Similarly, lycopene assessed by RRS was
      significantly correlated with lycopene assessed by HPLC of dermal biopsies (r =
      0.74, P < 0.0001). CONCLUSION: RRS is a feasible and valid method for
      noninvasively assessing dermal carotenoids as a biomarker for studies of
      nutrition and health.

PMID- 20685955
TI  - An update on pharmacological interventions for diabetic foot ulcers.
AB  - Diabetic foot ulcers are the most common lower extremity complications of
      diabetes. Peripheral neuropathy and peripheral vascular disease are the
      underlying risk factors for diabetic foot ulcers, subsequently leading to
      infections and requiring antimicrobial therapy for the management of the disease.
      Each risk factor is a target for clinical intervention, with the intent to delay
      or prevent disease progression to amputation. The effective therapy includes
      interdisciplinary care, which involves optimized pharmacological interventions in
      concert with other treatments such as debridement strategies and specialized
      wound dressings. The pharmacological therapy alone cannot lead to successful
      therapy, and therefore, these supplementary techniques/modalities should not be
      overlooked. It is therefore the aim of this report to review various
      pharmacological interventions, specific to the diabetic foot and wound healing,
      along with incorporation of advanced therapies required to achieve a multifaceted
      treatment of diabetic foot ulcers and provide basis for superior drugs as well as
      drug delivery systems.

PMID- 20685956
TI  - DMDM: domain mapping of disease mutations.
AB  - Domain mapping of disease mutations (DMDM) is a database in which each disease
      mutation can be displayed by its gene, protein or domain location. DMDM provides
      a unique domain-level view where all human coding mutations are mapped on the
      protein domain. To build DMDM, all human proteins were aligned to a database of
      conserved protein domains using a Hidden Markov Model-based sequence alignment
      tool (HMMer). The resulting protein-domain alignments were used to provide a
      domain location for all available human disease mutations and polymorphisms. The
      number of disease mutations and polymorphisms in each domain position are
      displayed alongside other relevant functional information (e.g. the binding and
      catalytic activity of the site and the conservation of that domain location).
      DMDM's protein domain view highlights molecular relationships among mutations
      from different diseases that might not be clearly observed with traditional gene
      centric visualization tools. AVAILABILITY: Freely available at
      http://bioinf.umbc.edu/dmdm.

PMID- 20685957
TI  - SPRINT: side-chain prediction inference toolbox for multistate protein design.
AB  - SPRINT is a software package that performs computational multistate protein
      design using state-of-the-art inference on probabilistic graphical models. The
      input to SPRINT is a list of protein structures, the rotamers modeled for each
      structure and the pre-calculated rotamer energies. Probabilistic inference is
      performed using the belief propagation or A* algorithms, and dead-end elimination
      can be applied as pre-processing. The output can either be a list of amino acid
      sequences simultaneously compatible with these structures, or probabilistic amino
      acid profiles compatible with the structures. In addition, higher order (e.g.
      pairwise) amino acid probabilities can also be predicted. Finally, SPRINT also
      has a module for protein side-chain prediction and single-state design.
      AVAILABILITY: The full C++ source code for SPRINT can be freely downloaded from
      http://www.protonet.cs.huji.ac.il/sprint.

PMID- 20685958
TI  - Ultra-fast FFT protein docking on graphics processors.
AB  - MOTIVATION: Modelling protein-protein interactions (PPIs) is an increasingly
      important aspect of structural bioinformatics. However, predicting PPIs using in
      silico docking techniques is computationally very expensive. Developing very fast
      protein docking tools will be useful for studying large-scale PPI networks, and
      could contribute to the rational design of new drugs. RESULTS: The Hex spherical
      polar Fourier protein docking algorithm has been implemented on Nvidia graphics
      processor units (GPUs). On a GTX 285 GPU, an exhaustive and densely sampled 6D
      docking search can be calculated in just 15 s using multiple 1D fast Fourier
      transforms (FFTs). This represents a 45-fold speed-up over the corresponding
      calculation on a single CPU, being at least two orders of magnitude times faster
      than a similar CPU calculation using ZDOCK 3.0.1, and estimated to be at least
      three orders of magnitude faster than the GPU-accelerated version of PIPER on
      comparable hardware. Hence, for the first time, exhaustive FFT-based protein
      docking calculations may now be performed in a matter of seconds on a
      contemporary GPU. Three-dimensional Hex FFT correlations are also accelerated by
      the GPU, but the speed-up factor of only 2.5 is much less than that obtained with
      1D FFTs. Thus, the Hex algorithm appears to be especially well suited to exploit
      GPUs compared to conventional 3D FFT docking approaches. AVAILABILITY:
      http://hex.loria.fr/ and http://hexserver.loria.fr/.

PMID- 20685960
TI  - Ang2/fat-free is a conserved subunit of the Golgi-associated retrograde protein
      complex.
AB  - The Golgi-associated retrograde protein (GARP) complex mediates tethering and
      fusion of endosome-derived transport carriers to the trans-Golgi network (TGN).
      In the yeast Saccharomyces cerevisiae, GARP comprises four subunits named Vps51p,
      Vps52p, Vps53p, and Vps54p. Orthologues of the GARP subunits, except for Vps51p,
      have been identified in all other eukaryotes. A yeast two-hybrid screen of a
      human cDNA library yielded a phylogenetically conserved protein, Ang2/Fat-free,
      which interacts with human Vps52, Vps53 and Vps54. Human Ang2 is larger than
      yeast Vps51p, but exhibits significant homology in an N-terminal coiled-coil
      region that mediates assembly with other GARP subunits. Biochemical analyses show
      that human Ang2, Vps52, Vps53 and Vps54 form an obligatory 1:1:1:1 complex that
      strongly interacts with the regulatory Habc domain of the TGN SNARE, Syntaxin 6.
      Depletion of Ang2 or the GARP subunits similarly impairs protein retrieval to the
      TGN, lysosomal enzyme sorting, endosomal cholesterol traffic  and autophagy.
      These findings indicate that Ang2 is the missing component of the GARP complex in
      most eukaryotes.

PMID- 20685959
TI  - The double-stranded RNA-dependent protein kinase differentially regulates insulin
      receptor substrates 1 and 2 in HepG2 cells.
AB  - Initially identified to be activated upon virus infection, the double-stranded
      RNA-dependent protein kinase (PKR) is best known for triggering cell defense
      responses by phosphorylating eIF-2alpha, thus suppressing RNA translation. We as
      well as others showed that the phosphorylation of PKR is down-regulated by
      insulin. In the present study, we further uncovered a novel function of PKR in
      regulating the IRS proteins. We found that PKR up-regulates the inhibitory
      phosphorylation of IRS1 at Ser312, which suppresses the tyrosine phosphorylation
      of IRS1. This effect of PKR on the phosphorylation of IRS1 is mediated by two
      other protein kinases, JNK and IKK. In contrast, PKR regulates IRS2, another
      major IRS family protein in the liver, at the transcriptional rather than the
      posttranslational level, and this effect is mediated by the transcription factor,
      FoxO1, which has been previously shown to be regulated by insulin and plays a
      significant role in glucose homeostasis and energy metabolism. In summary, we
      found for the first time that initially known as a virus infection response gene,
      PKR regulates the upstream central transmitters of insulin signaling, IRS1 and
      IRS2, through different mechanisms.

PMID- 20685961
TI  - Vestigial is required during late-stage muscle differentiation in Drosophila
      melanogaster embryos.
AB  - The somatic muscles of Drosophila develop in a complex pattern that is repeated
      in each embryonic hemi-segment. During early development, progenitor cells fuse
      to form a syncytial muscle, which further differentiates via expression of muscle
      specific factors that induce specific responses to external signals to regulate
      late-stage processes such as migration and attachment. Initial communication
      between somatic muscles and the epidermal tendon cells is critical for both of
      these processes. However, later establishment of attachments between longitudinal
      muscles at the segmental borders is largely independent of the muscle-epidermal
      attachment signals, and relatively little is known about how this event is
      regulated. Using a combination of null mutations and a truncated version of Sd
      that binds Vg but not DNA, we show that Vestigial (Vg) is required in ventral
      longitudinal muscles to induce formation of stable intermuscular attachments. In
      several muscles, this activity may be independent of Sd. Furthermore, the cell
      specific differentiation events induced by Vg in two cells fated to form
      attachments are coordinated by Drosophila epidermal growth factor signaling.
      Thus, Vg is a key factor to induce specific changes in ventral longitudinal
      muscles 1-4 identity and is required for these cells to be competent to form
      stable intermuscular attachments with each other.

PMID- 20685962
TI  - Identification of a nuclear export signal in the catalytic subunit of AMP
      activated protein kinase.
AB  - The metabolic regulator AMP-activated protein kinase (AMPK) maintains cellular
      homeostasis through regulation of proteins involved in energy-producing and 
      consuming pathways. Although AMPK phosphorylation targets include cytoplasmic and
      nuclear proteins, the precise mechanisms that regulate AMPK localization, and
      thus its access to these substrates, are unclear. We identify highly conserved
      carboxy-terminal hydrophobic amino acids that function as a leptomycin B
      sensitive, CRM1-dependent nuclear export sequence (NES) in the AMPK catalytic
      subunit (AMPKalpha). When this sequence is modified AMPKalpha shows increased
      nuclear localization via a Ran-dependent import pathway. Cytoplasmic localization
      can be restored by substituting well-defined snurportin-1 or protein kinase A
      inhibitor (PKIA) CRM1-binding NESs into AMPKalpha. We demonstrate a functional
      requirement in vivo for the AMPKalpha carboxy-terminal NES, as transgenic
      Drosophila expressing AMPKalpha lacking this NES fail to rescue lethality of
      AMPKalpha null mutant flies and show decreased activation loop phosphorylation
      under heat-shock stress. Sequestered to the nucleus, this truncated protein shows
      highly reduced phosphorylation at the key Thr172 activation residue, suggesting
      that AMPK activation predominantly occurs in the cytoplasm under unstressed
      conditions. Thus, modulation of CRM1-mediated export of AMPKalpha via its C
      terminal NES provides an additional mechanism for cells to use in the regulation
      of AMPK activity and localization.

PMID- 20685963
TI  - Farnesylated nuclear proteins Kugelkern and lamin Dm0 affect nuclear morphology
      by directly interacting with the nuclear membrane.
AB  - Nuclear shape changes are observed during a variety of developmental processes,
      pathological conditions, and ageing. The mechanisms underlying nuclear shape
      changes in the above-mentioned situations have mostly remained unclear. To
      address the molecular mechanism behind nuclear shape changes, we analyzed how the
      farnesylated nuclear envelope proteins Kugelkern and lamin Dm0 affect the
      structure of the nuclear membrane. We found that Kugelkern and lamin Dm0 affect
      nuclear shape without requiring filament formation or the presence of a classical
      nuclear lamina. We also could show that the two proteins do not depend on a group
      of selected inner nuclear membrane proteins for their localization to the nuclear
      envelope. Surprisingly, we found that farnesylated Kugelkern and lamin Dm0
      protein constructs change the morphology of protein-free liposomes. Based on
      these findings, we propose that farnesylated proteins of the nuclear membrane
      induce nuclear shape changes by being asymmetrically inserted into the
      phospholipid bilayer via their farnesylated C-terminal part.

PMID- 20685964
TI  - A novel Pzg-NURF complex regulates Notch target gene activity.
AB  - Drosophila putzig was identified as a member of the TRF2-DREF complex that is
      involved in core promoter selection. Additionally, putzig regulates Notch
      signaling, however independently of DREF. Here, we show that Putzig associates
      with the NURF complex. Loss of any NURF component including the NURF-specific
      subunit Nurf 301 impedes binding of Putzig to Notch target genes, suggesting that
      NURF recruits Putzig to these sites. Accordingly, Putzig can be copurified with
      any NURF member. Moreover, Nurf 301 mutants show reduced Notch target gene
      activity and enhance Notch mutant phenotypes. These data suggest a novel Putzig
      NURF chromatin complex required for epigenetic activation of Notch targets.

PMID- 20685965
TI  - Osmoprotective transcription factor NFAT5/TonEBP modulates nuclear factor-kappaB
      activity.
AB  - Tonicity-responsive binding-protein (TonEBP or NFAT5) is a widely expressed
      transcription factor whose activity is regulated by extracellular tonicity.
      TonEBP plays a key role in osmoprotection by binding to osmotic response
      element/TonE elements of genes that counteract the deleterious effects of cell
      shrinkage. Here, we show that in addition to this "classical" stimulation, TonEBP
      protects cells against hypertonicity by enhancing nuclear factor-kappaB (NF
      kappaB) activity. We show that hypertonicity enhances NF-kappaB stimulation by
      lipopolysaccharide but not tumor necrosis factor-alpha, and we demonstrate
      overlapping protein kinase B (Akt)-dependent signal transduction pathways
      elicited by hypertonicity and transforming growth factor-alpha. Activation of p38
      kinase by hypertonicity and downstream activation of Akt play key roles in TonEBP
      activity, IkappaBalpha degradation, and p65 nuclear translocation. TonEBP affects
      neither of these latter events and is itself insensitive to NF-kappaB signaling.
      Rather, we reveal a tonicity-dependent interaction between TonEBP and p65 and
      show that NF-kappaB activity is considerably enhanced after binding of NF-kappaB
      TonEBP complexes to kappaB elements of NF-kappaB-responsive genes. We demonstrate
      the key roles of TonEBP and Akt in renal collecting duct epithelial cells and in
      macrophages. These findings reveal a novel role for TonEBP and Akt in NF-kappaB
      activation on the onset of hypertonic challenge.

PMID- 20685966
TI  - Different localizations and cellular behaviors of leiomodin and tropomodulin in
      mature cardiomyocyte sarcomeres.
AB  - Leiomodin (Lmod) is a muscle-specific F-actin-nucleating protein that is related
      to the F-actin pointed-end-capping protein tropomodulin (Tmod). However, Lmod
      contains a unique ~150-residue C-terminal extension that is required for its
      strong nucleating activity. Overexpression or depletion of Lmod compromises
      sarcomere organization, but the mechanism by which Lmod contributes to myofibril
      assembly is not well understood. We show that Tmod and Lmod localize through
      fundamentally different mechanisms to the pointed ends of two distinct subsets of
      actin filaments in myofibrils. Tmod localizes to two narrow bands immediately
      adjacent to M-lines, whereas Lmod displays dynamic localization to two broader
      bands, which are generally more separated from M-lines. Lmod's localization and F
      actin nucleation activity are enhanced by interaction with tropomyosin. Unlike
      Tmod, the myofibril localization of Lmod depends on sustained muscle contraction
      and actin polymerization. We further show that Lmod expression correlates with
      the maturation of myofibrils in cultured cardiomyocytes and that it associates
      with sarcomeres only in differentiated myofibrils. Collectively, the data suggest
      that Lmod contributes to the final organization and maintenance of sarcomere
      architecture by promoting tropomyosin-dependent actin filament nucleation.

PMID- 20685967
TI  - Nitric oxide is involved in alkamide-induced lateral root development in
      Arabidopsis.
AB  - Alkamides are small bioactive lipid signals with a wide distribution in plants.
      In this report, the role of nitric oxide (NO) in the alterations induced by N
      isobutyl decanamide on the Arabidopsis (Arabidopsis thaliana) root system
      architecture (RSA) was investigated. We first compared the effects of N-isobutyl
      decanamide and NO donors sodium nitropruside (SNP) and S-nitroso-N
      acetylpenicillamine (SNAP) on root morphogenetic processes. Both N-isobutyl
      decanamide and NO donors modulated RSA in a similar way and in a dose-dependent
      manner, inhibiting primary root growth and promoting lateral root primordia (LRP)
      formation. RSA alterations induced by N-isobutyl decanamide correlated with NO
      accumulation in the primary root tip and in developing lateral roots.
      Morphogenetic effects of N-isobutyl decanamide decreased when NO scavengers were
      supplied to alkamide-treated seedlings. N-Isobutyl decanamide-regulated root
      architectural changes were also investigated in mutants defective in NO
      biosynthesis, nia1 nia2, and NO signalling, Atnoa1, and in the alkamide-resistant
      mutant drr1. The nia1 nia2 and Atnoa1 mutants were indistinguishable in primary
      root growth inhibition by the alkamide when compared with wild-type (WT)
      seedlings, but showed reduced lateral root responses. The drr1 mutant was less
      sensitive in both primary root growth inhibition and LRP induction by NO donors
      than WT seedlings. Detailed DR5:uidA and BA3:uidA marker analysis showed that N
      isobutyl decanamide and its interacting signals jasmonic acid and NO act
      downstream or independently of auxin-responsive gene expression to promote LRP
      formation. Our results provide compelling evidence that NO is an intermediate in
      alkamide signaling mediating RSA adjustment in Arabidopsis.

PMID- 20685968
TI  - Septum formation in amyloplasts produces compound granules in the rice endosperm
      and is regulated by plastid division proteins.
AB  - Storage tissues such as seed endosperm and tubers store starch in the form of
      granules in the amyloplast. In the rice (Oryza sativa) endosperm, each amyloplast
      produces compound granules consisting of several dozen polyhedral, sharp-edged
      and easily separable granules; whereas in other cereals, including wheat
      (Triticum aestivum), barley (Hordeum vulgare) and maize (Zea mays), each
      amyloplast synthesizes one granule. Despite extensive studies on mutants of
      starch synthesis in cereals, the molecular mechanisms involved in compound
      granule synthesis in rice have remained elusive. In this study, we expressed
      green fluorescent protein (GFP) fused to rice Brittle1 (BT1), an inner envelope
      membrane protein, to characterize dividing amyloplasts in the rice endosperm.
      Confocal microscopic analyses revealed that a septum-like structure, or cross
      wall, containing BT1-GFP divides granules in the amyloplast. Plastid division
      proteins including FtsZ, Min and PDV2 play significant roles not only in
      amyloplast division, but also in septum synthesis, suggesting that amyloplast
      division and septum synthesis are related processes that share common factors. We
      propose that successive septum syntheses which create sections inside the
      amyloplast and de novo granule synthesis in each section are primarily
      responsible for the synthesis of compound granules.

PMID- 20685969
TI  - Community- and genome-based views of plant-associated bacteria: plant-bacterial
      interactions in soybean and rice.
AB  - Diverse microorganisms are living as endophytes in plant tissues and as epiphytes
      on plant surfaces in nature. Questions about driving forces shaping the microbial
      community associated with plants remain unanswered. Because legumes developed
      systems to attain endosymbioses with rhizobia as well as mycorrhizae during their
      evolution, the above questions can be addressed using legume mutants relevant to
      genes for symbiosis. Analytical methods for the microbial community have recently
      been advanced by enrichment procedures of plant-associated microbes and culture
      independent analyses targeting the small subunit of rRNA in microbial ecology. In
      this review, we first deal with interdisciplinary works on the global diversity
      of bacteria associated with field-grown soybeans with different nodulation
      genotypes and nitrogen application. A subpopulation of Proteobacteria in aerial
      parts of soybean shoots was likely to be regulated through both the
      autoregulation system for plant-rhizobium symbiosis and the nitrogen signaling
      pathway, suggesting that legumes accommodate a taxonomically characteristic
      microbial community through unknown plant-microbe communications. In addition to
      the community views, we then show multiphasic analysis of a beneficial rice
      endophyte for comparative bacterial genomics and plant responses. The
      significance and perspectives of community- and genome-based approaches are
      discussed to achieve a better understanding of plant-microbe interactions.

PMID- 20685970
TI  - When feature-based attention distorts neural representations.

PMID- 20685971
TI  - Fragile X mental retardation protein is required for rapid experience-dependent
      regulation of the potassium channel Kv3.1b.
AB  - Fragile X mental retardation protein (FMRP) is an RNA-binding protein that
      regulates synaptic plasticity by repressing translation of specific mRNAs. We
      found that FMRP binds mRNA encoding the voltage-gated potassium channel Kv3.1b in
      brainstem synaptosomes. To explore the regulation of Kv3.1b by FMRP, we
      investigated Kv3.1b immunoreactivity and potassium currents in the auditory
      brainstem sound localization circuit of male mice. The unique features of this
      circuit allowed us to control neuronal activity in vivo by exposing animals to
      high-frequency, amplitude-modulated stimuli, which elicit predictable and
      stereotyped patterns of input to the anterior ventral cochlear nucleus (AVCN) and
      medial nucleus of the trapezoid body (MNTB). In wild-type (WT) animals, Kv3.1b is
      expressed along a tonotopic gradient in the MNTB, with highest levels in neurons
      at the medial, high-frequency end. At baseline, Fmr1(-/-) mice, which lack FMRP,
      displayed dramatically flattened tonotopicity in Kv3.1b immunoreactivity and K(+)
      currents relative to WT controls. Moreover, after 30 min of acoustic stimulation,
      levels of Kv3.1b immunoreactivity were significantly elevated in both the MNTB
      and AVCN of WT, but not Fmr1(-/-), mice. These results suggest that FMRP is
      necessary for maintenance of the gradient in Kv3.1b protein levels across the
      tonotopic axis of the MNTB, and are consistent with a role for FMRP as a
      repressor of protein translation. Using numerical simulations, we demonstrate
      that Kv3.1b tonotopicity may be required for accurate encoding of stimulus
      features such as modulation rate, and that disruption of this gradient, as occurs
      in Fmr1(-/-) animals, degrades processing of this information.

PMID- 20685972
TI  - SNARE force synchronizes synaptic vesicle fusion and controls the kinetics of
      quantal synaptic transmission.
AB  - Neuronal communication relies on rapid and discrete intercellular signaling but
      neither the molecular mechanisms of the exocytotic machinery that define the
      timing of the action potential-evoked response nor those controlling the kinetics
      of transmitter release from single synaptic vesicles are known. Here, we
      investigate how interference with the putative force transduction between the
      complex-forming SNARE (soluble N-ethylamide-sensitive factor attachment protein
      receptor) domain and the transmembrane anchor of synaptobrevin II (SybII) affects
      action potential-evoked currents and spontaneous, quantal transmitter release at
      mouse hippocampal synapses. The results indicate that SybII-generated membrane
      stress effectively determines the kinetics of the action potential-evoked
      response and show that SNARE force modulates the concentration profile of cleft
      glutamate by controlling the rate of transmitter release from the single synaptic
      vesicle. Thus, multiple SybII actions determine the exquisite temporal regulation
      of neuronal signaling.

PMID- 20685973
TI  - Prostatic acid phosphatase reduces thermal sensitivity and chronic pain
      sensitization by depleting phosphatidylinositol 4,5-bisphosphate.
AB  - Prostatic acid phosphatase (PAP) is expressed in nociceptive dorsal root ganglion
      (DRG) neurons, functions as an ectonucleotidase, and generates adenosine
      extracellularly. Here, we found that PAP inhibits noxious thermal sensitivity and
      sensitization that is associated with chronic pain through sustained activation
      of the adenosine A(1) receptor (A(1)R) and phospholipase C-mediated depletion of
      phosphatidylinositol 4,5-bisphosphate (PIP(2)). In mice, intrathecal injection of
      PAP reduced PIP(2) levels in DRGs, inhibited thermosensation through TRPV1, and
      enduringly reduced thermal hyperalgesia and mechanical allodynia caused by
      inflammation, nerve injury, and pronociceptive receptor activation. This included
      inhibitory effects on lysophosphatidic acid, purinergic (ATP), bradykinin, and
      protease-activated (thrombin) receptors. Conversely, PIP(2) levels were
      significantly elevated in DRGs from Pap(-/-) mice, and this correlated with
      enhanced thermal hyperalgesia and mechanical allodynia in Pap(-/-) mice. To
      directly test the importance of PIP(2) in nociception, we intrathecally injected
      PIP(2) into mice. This transiently (2 h) elevated PIP(2) levels in lumbar DRGs
      and transiently (2 h) enhanced thermosensation. Additionally, thermal
      hyperalgesia and mechanical allodynia were enduringly enhanced when PIP(2) levels
      were elevated coincident with injury/pronociceptive receptor stimulation.
      Nociceptive sensitization was not affected if PIP(2) levels were elevated in the
      absence of ongoing pronociceptive receptor stimulation. Together, our data
      suggest that PIP(2) levels in DRGs directly influence thermosensation and the
      magnitude of nociceptive sensitization. Moreover, our data suggest there is an
      underlying "phosphoinositide tone" that can be manipulated by an adenosine
      generating ectonucleotidase. This tone regulates how effectively acute
      nociceptive insults promote the transition to chronic pain.

PMID- 20685974
TI  - Motivated cognitive control: reward incentives modulate preparatory neural
      activity during task-switching.
AB  - It is increasingly appreciated that executive control processes need to be
      understood in terms of motivational as well as cognitive mechanisms. The current
      study examined the impact of performance-contingent reward incentives (monetary
      bonuses) on neural activity dynamics during cued task-switching performance.
      Behavioral measures indicated that performance was improved and task-switch costs
      selectively reduced on incentive trials. Trial-by-trial fluctuations in incentive
      value were associated with activation in reward-related brain regions
      (dopaminergic midbrain, paracingulate cortex) and also modulated the dynamics of
      switch-selective activation in the brain cognitive control network. Within
      lateral prefrontal cortex (PFC), both additive (inferior frontal junction) and
      interactive [dorsolateral PFC (DLPFC)] incentive effects were observed. In DLPFC,
      incentive modulation of activation predicted task-switching behavioral
      performance, but with hemispherically dissociable effects. Furthermore, in left
      DLPFC, incentive modulation specifically enhanced task-cue-related activation,
      and this activation in turn predicted that the trial would be subsequently
      rewarded (because of optimal performance). The results suggest that motivational
      incentives have a selective effect on brain regions that subserve cognitive
      control processes during task-switching and, moreover, that one mechanism of
      effect might be the enhancement of cue-related task preparation within left
      DLPFC.

PMID- 20685975
TI  - Functional magnetic resonance imaging reveals the neural substrates of arm
      transport and grip formation in reach-to-grasp actions in humans.
AB  - Picking up a cup requires transporting the arm to the cup (transport component)
      and preshaping the hand appropriately to grasp the handle (grip component). Here,
      we used functional magnetic resonance imaging to examine the human neural
      substrates of the transport component and its relationship with the grip
      component. Participants were shown three-dimensional objects placed either at a
      near location, adjacent to the hand, or at a far location, within reach but not
      adjacent to the hand. Participants performed three tasks at each location as
      follows: (1) touching the object with the knuckles of the right hand; (2)
      grasping the object with the right hand; or (3) passively viewing the object. The
      transport component was manipulated by positioning the object in the far versus
      the near location. The grip component was manipulated by asking participants to
      grasp the object versus touching it. For the first time, we have identified the
      neural substrates of the transport component, which include the superior parieto
      occipital cortex and the rostral superior parietal lobule. Consistent with past
      studies, we found specialization for the grip component in bilateral anterior
      intraparietal sulcus and left ventral premotor cortex; now, however, we also find
      activity for the grasp even when no transport is involved. In addition to finding
      areas specialized for the transport and grip components in parietal cortex, we
      found an integration of the two components in dorsal premotor cortex and
      supplementary motor areas, two regions that may be important for the coordination
      of reach and grasp.

PMID- 20685976
TI  - Long and short multifunicular projections of sacral neurons are activated by
      sensory input to produce locomotor activity in the absence of supraspinal
      control.
AB  - Afferent input from load and joint receptors has been shown to reactivate the
      central pattern generators for locomotion (CPGs) in spinal cord injury patients
      and thereby improve their motor function and mobility. Elucidation of the
      pathways interposed between the afferents and CPGs is critical for the
      determination of the capacity of sensory input to activate the CPGs when the
      continuity of the white matter tracts is impaired following spinal cord injury.
      Using electrophysiological recordings, confocal imaging studies of spinal neurons
      and surgical manipulations of the white matter, we show that the capacity of
      sacrocaudal afferent (SCA) input to produce locomotor activity in isolated rat
      spinal cords depends not only on long ascending pathways, but also on recruitment
      of sacral proprioneurons interposed between the second order neurons and the
      hindlimb CPGs. We argue that large heterogeneous populations of second-order and
      proprioneurons whose crossed and uncrossed axons project rostrally through the
      ventral, ventrolateral/lateral and dorsolateral white matter funiculi contribute
      to the generation of the rhythm by the stimulated sacrocaudal input. The complex
      organization and multiple projection patterns of these populations enable the
      sacrocaudal afferent input to activate the CPGs even if the white matter pathways
      are severely damaged. Further studies are required to clarify the mechanisms
      involved in SCA-induced locomotor activity and assess its potential use for the
      rescue of lost motor functions after spinal cord injury.

PMID- 20685977
TI  - The representation of S-cone signals in primary visual cortex.
AB  - Recent studies of middle-wavelength-sensitive and long-wavelength-sensitive cone
      responses in primate primary visual cortex (V1) have challenged the view that
      color and form are represented by distinct neuronal populations. Individual V1
      neurons exhibit hallmarks of both color and form processing (cone opponency and
      orientation selectivity), and many display cone interactions that do not fit
      classic chromatic/achromatic classifications. Comparable analysis of short
      wavelength-sensitive (S) cone responses has yet to be achieved and is of
      considerable interest because S-cones are the basis for the primordial mammalian
      chromatic pathway. Using intrinsic and two-photon imaging techniques in the tree
      shrew, we assessed the properties of V1 layer 2/3 neurons responsive to S-cone
      stimulation. These responses were orientation selective, exhibited distinct
      spatiotemporal properties, and reflected integration of S-cone inputs via
      opponent, summing, and intermediate configurations. Our observations support a
      common framework for the representation of cone signals in V1, one that endows
      orientation-selective neurons with a range of chromatic, achromatic, and mixed
      response properties.

PMID- 20685978
TI  - Basolateral amygdala cdk5 activity mediates consolidation and reconsolidation of
      memories for cocaine cues.
AB  - Cocaine use and relapse involves learned associations between cocaine-associated
      environmental contexts and discrete stimuli and cocaine effects. Initially, these
      contextual and discrete cues undergo memory consolidation after being paired with
      cocaine exposure. During abstinence, cocaine cue memories can undergo memory
      reconsolidation after cue exposure without the drug. We used a conditioned place
      preference (CPP) procedure in rats to study the role of neuronal protein kinase
      cyclin-dependent kinase 5 (Cdk5) in consolidation and reconsolidation of cocaine
      cue memories. We found that the expression of cocaine CPP in drug-free tests 1 d
      after CPP training (four pairings of 10 mg/kg cocaine with one context and four
      pairings of saline with a different context) increased Cdk5 activity, and levels
      of the Cdk5 activator p35 in basolateral but not central amygdala. We also found
      that basolateral (but not central) amygdala injections of the Cdk5 inhibitor beta
      butyrolactone (100 ng/side) immediately (but not 6 h) after cocaine-context
      pairings during training prevented subsequent cocaine CPP expression. After
      training, acute basolateral (but not central) amygdala beta-butyrolactone
      injections immediately before testing prevented the expression of cocaine CPP;
      this effect was also observed on a second test performed 1 d later, suggesting an
      effect on reconsolidation of cocaine cue memories. In support, basolateral beta
      butyrolactone injections, given immediately (but not 6 h) after a single exposure
      to the cocaine-paired context, prevented cocaine CPP expression 1 and 14 d after
      the injections. Results indicate that basolateral amygdala Cdk5 activity is
      critical for consolidation and reconsolidation of the memories of cocaine
      associated environmental cues.

PMID- 20685979
TI  - Ca(v)3.2 T-type Ca2+ channel-dependent activation of ERK in paraventricular
      thalamus modulates acid-induced chronic muscle pain.
AB  - Treatments for chronic musculoskeletal pain, such as lower back pain,
      fibromyalgia, and myofascial pain syndrome, remain inadequate because of our poor
      understanding of the mechanisms that underlie these conditions. Although T-type
      Ca2+ channels (T-channels) have been implicated in peripheral and central pain
      sensory pathways, their role in chronic musculoskeletal pain is still unclear.
      Here, we show that acid-induced chronic mechanical hyperalgesia develops in
      Ca(v)3.1-deficient and wild-type but not in Ca(v)3.2-deficient male and female
      mice. We also show that T-channels are required for the initiation, but not
      maintenance, of acid-induced chronic muscle pain. Blocking T-channels using
      ethosuximide prevented chronic mechanical hyperalgesia in wild-type mice when
      administered intraperitoneally or intracerebroventricularly, but not
      intramuscularly or intrathecally. Furthermore, we found an acid-induced, Ca(v)3.2
      T-channel-dependent activation of ERK (extracellular signal-regulated kinase) in
      the anterior nucleus of paraventricular thalamus (PVA), and prevention of the ERK
      activation abolished the chronic mechanical hyperalgesia. Our findings suggest
      that Ca(v)3.2 T-channel-dependent activation of ERK in PVA is required for the
      development of acid-induced chronic mechanical hyperalgesia.

PMID- 20685980
TI  - Generation and therapeutic efficacy of highly oligomer-specific beta-amyloid
      antibodies.
AB  - Oligomers of the beta-amyloid (Abeta) peptide have been indicated in early
      neuropathologic changes in Alzheimer's disease. Here, we present a synthetic
      Abeta(20-42) oligomer (named globulomer) with a different conformation to
      monomeric and fibrillar Abeta peptide, enabling the generation of highly Abeta
      oligomer-specific monoclonal antibodies. The globulomer-derived antibodies
      specifically detect oligomeric but not monomeric or fibrillar Abeta in various
      Abeta preparations. The globulomer-specific antibody A-887755 was able to prevent
      Abeta oligomer binding and dynamin cleavage in primary hippocampal neurons and to
      reverse globulomer-induced reduced synaptic transmission. In amyloid precursor
      protein (APP) transgenic mice, vaccination with Abeta globulomer and treatment
      with A-887755 improved novel object recognition. The cognitive improvement is
      likely attributable to reversing a deficit in hippocampal synaptic spine density
      in APP transgenic mice as observed after treatment with A-887755. Our findings
      demonstrate that selective reduction of Abeta oligomers by immunotherapy is
      sufficient to normalize cognitive behavior and synaptic deficits in APP
      transgenic mice.

PMID- 20685981
TI  - Power-law dynamics in an auditory-nerve model can account for neural adaptation
      to sound-level statistics.
AB  - Neurons in the auditory system respond to recent stimulus-level history by
      adapting their response functions according to the statistics of the stimulus,
      partially alleviating the so-called "dynamic-range problem." However, the
      mechanism and source of this adaptation along the auditory pathway remain
      unknown. Inclusion of power-law dynamics in a phenomenological model of the inner
      hair cell (IHC)-auditory nerve (AN) synapse successfully explained neural
      adaptation to sound-level statistics, including the time course of adaptation of
      the mean firing rate and changes in the dynamic range observed in AN responses. A
      direct comparison between model responses to a dynamic stimulus and to an
      "inversely gated" static background suggested that AN dynamic-range adaptation
      largely results from the adaptation produced by the response history. These
      results support the hypothesis that the potential mechanism underlying the
      dynamic-range adaptation observed at the level of the auditory nerve is located
      peripheral to the spike generation mechanism and central to the IHC receptor
      potential.

PMID- 20685982
TI  - Centrosome motility is essential for initial axon formation in the neocortex.
AB  - The mechanisms underlying the normal development of neuronal morphology remain a
      fundamental question in neurobiology. Studies in cultured neurons have suggested
      that the position of the centrosome and the Golgi may predict the site of axon
      outgrowth. During neuronal migration in the developing cortex, however, the
      centrosome and Golgi are oriented toward the cortical plate at a time when axons
      grow toward the ventricular zone. In the current work, we use in situ live
      imaging to demonstrate that the centrosome and the accompanying polarized
      cytoplasm exhibit apical translocation in newborn cortical neurons preceding
      initial axon outgrowth. Disruption of centrosomal activity or downregulation of
      the centriolar satellite protein PCM-1 affects axon formation. We further show
      that downregulation of the centrosomal protein Cep120 impairs microtubule
      organization, resulting in increased centrosome motility. Decreased centrosome
      motility resulting from microtubule stabilization causes an aberrant centrosomal
      localization, leading to misplaced axonal outgrowth. Our results reveal the
      dynamic nature of the centrosome in developing cortical neurons, and implicate
      centrosome translocation and microtubule organization during the multipolar stage
      as important determinants of axon formation.

PMID- 20685983
TI  - Triphasic dynamics of stimulus-dependent information flow between single neurons
      in macaque inferior temporal cortex.
AB  - The functional connectivity between cortical neurons is not static and is known
      to exhibit contextual modulations in terms of the coupling strength. Here we
      hypothesized that the information flow in a cortical local circuit exhibits
      complex forward-and-back dynamics, and conducted Granger causality analysis
      between the neuronal spike trains that were simultaneously recorded from macaque
      inferior temporal (IT) cortex while the animals performed a visual object
      discrimination task. Spikes from neuron pairs with a displaced peak on the cross
      correlogram (CCG) showed Granger causality in the gamma-frequency range (30-80
      Hz) with the dominance in the direction consistent with the CCG peak (forward
      direction). Although, in a classical view, the displaced CCG peak has been
      interpreted as an indicative of a pauci-synaptic serial linkage, temporal
      dynamics of the gamma Granger causality after stimulus onset exhibited a more
      complex triphasic pattern, with a transient forward component followed by a
      slowly developing backward component and subsequent reappearance of the forward
      component. These triphasic dynamics of causality were not explained by the firing
      rate dynamics and were not observed for cell pairs that exhibited a center peak
      on the CCG. Furthermore, temporal dynamics of Granger causality depended on the
      feature configuration within the presented object. Together, these results
      demonstrate that the classical view of functional connectivity could be expanded
      to incorporate more complex forward-and-back dynamics and also imply that
      multistage processing in the recognition of visual objects might be implemented
      by multiphasic dynamics of directional information flow between single neurons in
      a local circuit in the IT cortex.

PMID- 20685984
TI  - Group III metabotropic glutamate receptors inhibit startle-mediating giant
      neurons in the caudal pontine reticular nucleus but do not mediate synaptic
      depression/short-term habituation of startle.
AB  - Short-term habituation is a basic form of learning that is analyzed in different
      species and using different behavioral models. Previous studies on mechanisms of
      short-term habituation yielded evidence for a potential role of group III
      metabotropic glutamate receptors (mGluRIIIs). Here we tested the hypothesis that
      mGluRIII mediate short-term habituation of startle in rats, combining
      electrophysiological experiments in vitro with behavioral studies in vivo. We
      applied different mGluRIII agonists and antagonists on rat brainstem slices while
      recording from startle-mediating neurons in the caudal pontine reticular nucleus
      (PnC) and monitoring synaptic depression presumably underlying habituation.
      Furthermore, we injected the mGluRIII antagonist (RS)-alpha
      phosphonophenylglycine (MPPG) and the agonist L-(+)-2-amino-4-phosphonobutyric
      acid (L-AP4) into the PnC of rats in vivo and measured its effect on startle
      habituation. Our results show that activation of mGluRIIIs in the PnC strongly
      inhibits startle-mediating giant neurons in vitro. Accordingly, L-AP4 reduced
      startle responses in vivo. However, synaptic depression in the slice was not
      disrupted by mGluRIII antagonists or agonists. Correspondingly, the in vivo
      application of the mGluRIII antagonist MPPG failed to show any effect on short
      term habituation of startle responses. We therefore conclude that mGluRs are
      expressed within the primary startle pathway and that they inhibit startle
      responses upon activation; however, this inhibition does not play any role in
      synaptic depression and short-term habituation of startle. This is in contrast to
      the role of mGluRIIIs in other forms of habituation and supports the notion that
      there are different mechanisms involved in habituation of sensory-evoked
      behaviors.

PMID- 20685986
TI  - Lipoprotein particles cross the blood-brain barrier in Drosophila.
AB  - The blood-brain barrier (BBB) regulates passage of nutrients and signaling
      molecules from the circulation into the brain. Whether lipoproteins cross the BBB
      in vivo has been controversial, and no clear requirement for circulating
      lipoproteins in brain development has been shown. We address these issues in
      Drosophila, which has an functionally conserved BBB, and lipoproteins that
      resemble those of vertebrates. We show that the Drosophila lipoprotein lipophorin
      exists in two isoforms. Both isoforms cross the BBB, but accumulate on distinct
      subsets of cells within the brain. In addition to acting as a lipid carrier,
      lipophorin carries both sterol-linked and GPI-linked proteins into the
      circulation and transports them across the BBB. Finally, lipophorin promotes
      neuroblast proliferation by a mechanism that does not depend on delivery of
      dietary lipids. Transport of lipophorin and its cargo across the BBB represents a
      novel mechanism by which peripherally synthesized proteins might enter the brain
      and influence its development. Furthermore, lipid-linkage may be an efficient
      method to transport therapeutic molecules across the BBB.

PMID- 20685985
TI  - Biochemical and functional interaction of disrupted-in-schizophrenia 1 and
      amyloid precursor protein regulates neuronal migration during mammalian cortical
      development.
AB  - Although clinically distinct, schizophrenia and Alzheimer's disease are common
      and devastating disorders that profoundly impair cognitive function. For
      Alzheimer's disease, key mechanistic insights have emerged from genetic studies
      that identified causative mutations in amyloid precursor protein (APP) and
      presenilin. Several genes have been associated with schizophrenia and other major
      psychoses, and understanding their normal functions will help elucidate the
      underlying causes of these disorders. One such gene is disrupted-in-schizophrenia
      1 (DISC1). DISC1 and APP have been implicated separately in cortical development,
      with each having roles in both neuronal migration and neurite outgrowth. Here, we
      report a previously unrecognized biochemical and functional interaction between
      DISC1 and APP. Using in utero electroporation in the living rat brain, we show
      that DISC1 acts downstream of APP and Disabled-1 to regulate cortical precursor
      cell migration. Specifically, overexpression of DISC1 rescues the migration
      defect caused by a loss of APP expression. Moreover, knockdown of APP in cultured
      embryonic neurons results in altered subcellular localization of DISC1. Using
      transfected cells and normal brain tissue, we show that APP and DISC1
      coimmunoprecipitate and that the intracellular domain of APP interacts with the N
      terminal domain of DISC1. Based on these findings, we hypothesize that the APP
      cytoplasmic region transiently interacts with DISC1 to help regulate the
      translocation of DISC1 to the centrosome, where it plays a key role in
      controlling neuronal migration during cortical development.

PMID- 20685987
TI  - Selection of prime actor in humans during bimanual object manipulation.
AB  - In bimanual object manipulation tasks, people flexibly assign one hand as a prime
      actor while the other assists. Little is known, however, about the neural
      mechanisms deciding the role assignment. We addressed this issue in a task in
      which participants moved a cursor to hit targets on a screen by applying
      precisely coupled symmetrical opposing linear and twist forces on a tool held
      freely between the hands. In trials presented in an unpredictable order, the
      action of either the left or the right hand was spatially congruent with the
      cursor movements, which automatically rendered the left or right hand the
      dominant actor, respectively. Functional magnetic resonance imaging indicated
      that the hand-selection process engaged prefrontal cortical areas belonging to an
      executive control network presumed critical for judgment and decision-making and
      to a salience network attributed to evaluation of utility of actions. Task
      initiation, which involved switching between task sets, had a superordinate role
      with reference to hand selection. Behavioral and brain imaging data indicated
      that participants initially expressed two competing action representations,
      matching either mapping rule, before selecting the appropriate one based on the
      consequences of the initial manual actions. We conclude that implicit processes
      engaging the prefrontal cortex reconcile selections among action representations
      that compete for the establishment of a dominant actor in bimanual object
      manipulation tasks. The representation selected is the one that optimizes
      performance by relying on the superior capacity of the brain to process spatial
      congruent, as opposed to noncongruent, mappings between manual actions and
      desired movement goals.

PMID- 20685988
TI  - Negative valence widens generalization of learning.
AB  - Learning includes the ability to generalize to new situations and respond to
      similar, yet not identical stimuli. We use stimulus generalization in humans to
      show that tones that were negatively reinforced induce wider generalization
      curves than tones that were positively reinforced, and these in turn induce wider
      curves than neutral memory. Importantly, these wider generalization curves
      persist even if outcomes for all tones are made identical, indicating that the
      learning induced a perceptual change, and not merely a decision bias. Moreover,
      it persists after taking into account loss-aversion, suggesting it is a result of
      valence per se, and not intensity that reflects overweighting of the aversive
      stimuli. This effect of emotional valence on learning suggests different
      locations of plasticity and network mechanisms in the brain. Particularly, it
      suggests that brain areas that mediate reinforcement and emotions are involved
      during the learning process to induce a neural representation that can support
      this broader behavioral generalization. In addition, these findings highlight a
      model for anxiety and trauma disorders in which aversive experiences affect more
      than they should, sometimes even in seemingly irrational situations.

PMID- 20685989
TI  - Fine thermotactic discrimination between the optimal and slightly cooler
      temperatures via a TRPV channel in chordotonal neurons.
AB  - Animals select their optimal environmental temperature, even when faced with
      alternatives that differ only slightly. This behavior is critical as small
      differences in temperature of only several degrees can have a profound effect on
      the survival and rate of development of poikilothermic animals, such as the fruit
      fly. Here, we demonstrate that Drosophila larvae choose their preferred
      temperature of 17.5 degrees C over slightly cooler temperatures (14-16 degrees C)
      through activation of chordotonal neurons. Mutations affecting a transient
      receptor potential (TRP) vanilloid channel, Inactive (Iav), which is expressed
      specifically in chordotonal neurons, eliminated the ability to choose 17.5
      degrees C over 14-16 degrees C. The impairment in selecting 17.5 degrees C
      resulted from absence of an avoidance response, which is normally mediated by an
      increase in turns at the lower temperatures. We conclude that the decision to
      select the preferred over slightly cooler temperatures requires iav and is
      achieved by activating chordotonal neurons, which in turn induces repulsive
      behaviors, due to an increase in high angle turns.

PMID- 20685990
TI  - Stress-evoked tyrosine phosphorylation of signal regulatory protein alpha
      regulates behavioral immobility in the forced swim test.
AB  - Severe stress induces changes in neuronal function that are implicated in stress
      related disorders such as depression. The molecular mechanisms underlying the
      response of the brain to stress remain primarily unknown, however. Signal
      regulatory protein alpha (SIRPalpha) is an Ig-superfamily protein that undergoes
      tyrosine phosphorylation and binds the protein tyrosine phosphatase Shp2. Here we
      show that mice expressing a form of SIRPalpha that lacks most of the cytoplasmic
      region manifest prolonged immobility (depression-like behavior) in the forced
      swim (FS) test. FS stress induced marked tyrosine phosphorylation of SIRPalpha in
      the brain of wild-type mice through activation of Src family kinases. The
      SIRPalpha ligand CD47 was important for such SIRPalpha phosphorylation, and CD47
      deficient mice also manifested prolonged immobility in the FS test. Moreover, FS
      stress-induced tyrosine phosphorylation of both the NR2B subunit of the NMDA
      subtype of glutamate receptor and the K+-channel subunit Kvbeta2 was regulated by
      SIRPalpha. Thus, tyrosine phosphorylation of SIRPalpha is important for
      regulation of depression-like behavior in the response of the brain to stress.

PMID- 20685991
TI  - Notch1 is required for maintenance of the reservoir of adult hippocampal stem
      cells.
AB  - Notch1 regulates neural stem cell (NSC) number during development, but its role
      in adult neurogenesis is unclear. We generated nestin-CreER(T2)/R26R
      YFP/Notch1(loxP/loxP) [Notch1inducible knock-out (iKO)] mice to allow tamoxifen
      (TAM)-inducible elimination of Notch1 and concomitant expression of yellow
      fluorescent protein (YFP) in nestin-expressing Type-1 NSCs and their progeny in
      the adult hippocampal subgranular zone (SGZ). Consistent with previous research,
      YFP+ cells in all stages of neurogenesis were evident in the subgranular zone
      (SGZ) of wild-type (WT) mice (nestin-CreER(T2)/R26R-YFP/Notch1(w/w)) after
      tamoxifen (post-TAM), producing adult-generated YFP+ dentate gyrus neurons.
      Compared with WT littermates, Notch1 iKO mice had similar numbers of total SGZ
      YFP+ cells 13 and 30 d post-TAM but had significantly fewer SGZ YFP+ cells 60 and
      90 d post-TAM. Significantly fewer YFP+ Type-1 NSCs and transiently amplifying
      progenitors (TAPs) resulted in generation of fewer YFP+ granule neurons in Notch1
      iKO mice. Strikingly, 30 d of running rescued this deficit, as the total YFP+
      cell number in Notch iKO mice was equivalent to WT levels. This was even more
      notable given the persistent deficits in the Type-1 NSC and TAP reservoirs. Our
      data show that Notch1 signaling is required to maintain a reservoir of
      undifferentiated cells and ensure continuity of adult hippocampal neurogenesis,
      but that alternative Notch- and Type-1 NSC-independent pathways compensate in
      response to physical activity. These data shed light on the complex relationship
      between Type-1 NSCs, adult neurogenesis, the neurogenic niche, and environmental
      stimuli.

PMID- 20685992
TI  - Attentional facilitation throughout human visual cortex lingers in retinotopic
      coordinates after eye movements.
AB  - With each eye movement, the image of the world received by the visual system
      changes dramatically. To maintain stable spatiotopic (world-centered) visual
      representations, the retinotopic (eye-centered) coordinates of visual stimuli are
      continually remapped, even before the eye movement is completed. Recent
      psychophysical work has suggested that updating of attended locations occurs as
      well, although on a slower timescale, such that sustained attention lingers in
      retinotopic coordinates for several hundred milliseconds after each saccade. To
      explore where and when this "retinotopic attentional trace" resides in the
      cortical visual processing hierarchy, we conducted complementary functional
      magnetic resonance imaging and event-related potential (ERP) experiments using a
      novel gaze-contingent task. Human subjects executed visually guided saccades
      while covertly monitoring a fixed spatiotopic target location. Although subjects
      responded only to stimuli appearing at the attended spatiotopic location, blood
      oxygen level-dependent responses to stimuli appearing after the eye movement at
      the previously, but no longer, attended retinotopic location were enhanced in
      visual cortical area V4 and throughout visual cortex. This retinotopic
      attentional trace was also detectable with higher temporal resolution in the
      anterior N1 component of the ERP data, a well established signature of
      attentional modulation. Together, these results demonstrate that, when top-down
      spatiotopic signals act to redirect visuospatial attention to new retinotopic
      locations after eye movements, facilitation transiently persists in the cortical
      regions representing the previously relevant retinotopic location.

PMID- 20685994
TI  - Causality attribution biases oculomotor responses.
AB  - When viewing one object move after being struck by another, humans perceive that
      the action of the first object "caused" the motion of the second, not that the
      two events occurred independently. Although established as a perceptual and
      linguistic concept, it is not yet known whether the notion of causality exists as
      a fundamental, preattentional "Gestalt" that can influence predictive motor
      processes. Therefore, eye movements of human observers were measured while
      viewing a display in which a launcher impacted a tool to trigger the motion of a
      second "reaction" target. The reaction target could move either in the direction
      predicted by transfer of momentum after the collision ("causal") or in a
      different direction ("noncausal"), with equal probability. Control trials were
      also performed with identical target motion, either with a 100 ms time delay
      between the collision and reactive motion, or without the interposed tool.
      Subjects made significantly more predictive movements (smooth pursuit and
      saccades) in the causal direction during standard trials, and smooth pursuit
      latencies were also shorter overall. These trends were reduced or absent in
      control trials. In addition, pursuit latencies in the noncausal direction were
      longer during standard trials than during control trials. The results show that
      causal context has a strong influence on predictive movements.

PMID- 20685993
TI  - Temporal discounting of reward and the cost of time in motor control.
AB  - Why do movements take a characteristic amount of time, and why do diseases that
      affect the reward system alter control of movements? Suppose that the purpose of
      any movement is to position our body in a more rewarding state. People and other
      animals discount future reward as a hyperbolic function of time. Here, we show
      that across populations of people and monkeys there is a correlation between
      discounting of reward and control of movements. We consider saccadic eye
      movements and hypothesize that duration of a movement is equivalent to a delay of
      reward. The hyperbolic cost of this delay not only accounts for kinematics of
      saccades in adults, it also accounts for the faster saccades of children, who
      temporally discount reward more steeply. Our theory explains why saccade
      velocities increase when reward is elevated, and why disorders in the encoding of
      reward, for example in Parkinson's disease and schizophrenia, produce changes in
      saccade. We show that delay of reward elevates the cost of saccades, reducing
      velocities. Finally, we consider coordinated movements that include motion of
      eyes and head and find that their kinematics is also consistent with a
      hyperbolic, reward-dependent cost of time. Therefore, each voluntary movement
      carries a cost because its duration delays acquisition of reward. The cost
      depends on the value that the brain assigns to stimuli, and the rate at which it
      discounts this value in time. The motor commands that move our eyes reflect this
      cost of time.

PMID- 20685995
TI  - D-cycloserine reduces the context specificity of pavlovian extinction of cocaine
      cues through actions in the nucleus accumbens.
AB  - Extinction therapy has been proposed as a method to reduce the motivational
      impact of drug-associated cues to prevent relapse. Cue extinction therapy,
      however, takes place in a novel context (e.g., treatment facility), and is
      unlikely to be effective due to the context specificity of extinction. We tested
      the hypothesis that d-cycloserine (DCS), which enhances extinction in other
      procedures, would enhance extinction of cocaine-associated cues in a novel
      context to reduce cue-induced reinstatement. Male Sprague Dawley rats were
      trained to self-administer cocaine associated with a cue. The cue was later
      extinguished in the drug-taking context (context A) or a novel context (context
      B) using a Pavlovian cue extinction procedure designed to mimic human cue
      exposure therapy. DCS was administered systemically or into a specific brain
      region immediately following the cue extinction sessions to enhance the
      consolidation of extinction learning. We demonstrate that DCS given
      postextinction session in context B reduces reinstatement in context A,
      indicating a reduction in the context specificity of extinction learning. The
      effect of systemic DCS was recapitulated by administration of DCS into the
      nucleus accumbens core, but not in the basolateral amygdala, dorsal hippocampus,
      infralimbic or prelimbic prefrontal cortex. DCS treatment caused a reduction in
      cue-induced reinstatement only when it was given after cue extinction sessions,
      and not when given 1) in the absence of extinction or 2) after a brief memory
      reactivation session. A pharmacological method that can render extinction context
      independent may provide an innovative method to reduce cue-induced relapse in
      addicts and to study the neurobiology of addiction.

PMID- 20685996
TI  - The body inversion effect is mediated by face-selective, not body-selective,
      mechanisms.
AB  - Evidence suggesting that the brain has specialized mechanisms for processing
      human bodies include the discovery of body-selective brain areas and the
      behavioral body inversion effect (BIE). Interestingly, the BIE (worse
      discrimination of inverted vs upright bodies) disappears for headless bodies,
      implying a critical role of the head in this effect. Previous studies have shown
      that the face inversion effect is mediated by the fusiform face-selective area.
      Given the central role that the head plays in the behavioral BIE, we asked
      whether it is mediated by face-selective or body-selective areas. In two event
      related functional magnetic resonance-adaptation experiments, we examined the
      representation of upright and inverted bodies in category-selective
      occipitotemporal areas. In the first experiment we presented whole (faceless)
      bodies, while in the second we presented headless bodies. Both experiments
      consisted of pairs of upright and inverted bodies that were either the same or
      different in posture. Body-selective areas showed similar adaptation effects for
      upright and inverted whole or headless bodies, suggesting similar discrimination
      for the two orientations regardless of the head. In contrast, face-selective
      areas showed an adaptation effect to upright but not inverted bodies, and for
      whole but not for headless bodies. Thus, the response of the face-selective, but
      not body-selective areas, is consistent with the behavioral BIE in that it shows
      better discrimination for upright than inverted bodies, for whole but not for
      headless bodies. These results suggest a critical role for the head in the
      processing of human bodies.

PMID- 20685997
TI  - Quantitative relationships between huntingtin levels, polyglutamine length,
      inclusion body formation, and neuronal death provide novel insight into
      huntington's disease molecular pathogenesis.
AB  - An expanded polyglutamine (polyQ) stretch in the protein huntingtin (htt) induces
      self-aggregation into inclusion bodies (IBs) and causes Huntington's disease
      (HD). Defining precise relationships between early observable variables and
      neuronal death at the molecular and cellular levels should improve our
      understanding of HD pathogenesis. Here, we used an automated microscope that
      tracks thousands of neurons individually over their entire lifetime to quantify
      interconnected relationships between early variables, such as htt levels, polyQ
      length, and IB formation, and neuronal death in a primary striatal model of HD.
      The resulting model revealed that mutant htt increases the risk of death by
      tonically interfering with homeostatic coping mechanisms rather than producing
      accumulated damage to the neuron, htt toxicity is saturable, the rate-limiting
      steps for inclusion body formation and death can be traced to different
      conformational changes in monomeric htt, and IB formation reduces the impact of
      the starting levels of htt of a neuron on its risk of death. Finally, the model
      that emerges from our quantitative measurements places critical limits on the
      potential mechanisms by which mutant htt might induce neurodegeneration, which
      should help direct future research.

PMID- 20685999
TI  - A novel transient glutamatergic population migrating from the pallial-subpallial
      boundary contributes to neocortical development.
AB  - The generation of a precise number of neural cells and the determination of their
      laminar fate are tightly controlled processes during development of the cerebral
      cortex. Using genetic tracing in mice, we have identified a population of
      glutamatergic neurons generated by Dbx1-expressing progenitors at the pallial
      subpallial boundary predominantly at embryonic day 12.5 (E12.5) and subsequent to
      Cajal-Retzius cells. We show that these neurons migrate tangentially to populate
      the cortical plate (CP) at all rostrocaudal and mediolateral levels by E14.5. At
      birth, they homogeneously populate cortical areas and represent <5% of cortical
      cells. However, they are distributed into neocortical layers according to their
      birthdates and express the corresponding markers of glutamatergic differentiation
      (Tbr1, ER81, Cux2, Ctip2). Notably, this population dies massively by apoptosis
      at the completion of corticogenesis and represents 50% of dying neurons in the
      postnatal day 0 cortex. Specific genetic ablation of these transient Dbx1-derived
      CP neurons leads to a 20% decrease in neocortical cell numbers in perinatal
      animals. Our results show that a previously unidentified transient population of
      glutamatergic neurons migrates from extraneocortical regions over long distance
      from their generation site and participates in neocortical radial growth in a non
      cell-autonomous manner.

PMID- 20685998
TI  - LIM-homeobox gene Lhx5 is required for normal development of Cajal-Retzius cells.
AB  - Cajal-Retzius (C-R) cells play important roles in the lamination of the mammalian
      cortex via reelin secretion. The genetic mechanisms underlying the development of
      these neurons have just begun to be unraveled. Here, we show that two closely
      related LIM-homeobox genes Lhx1 and Lhx5 are expressed in reelin+ cells in
      various regions in the mouse telencephalon at or adjacent to sites where the C-R
      cells are generated, including the cortical hem, the mantle region of the
      septal/retrobulbar area, and the ventral pallium. Whereas Lhx5 is expressed in
      all of these reelin-expressing domains, Lhx1 is preferentially expressed in the
      septal area and in a continuous domain spanning from lateral olfactory region to
      caudomedial territories. Genetic ablation of Lhx5 results in decreased reelin+
      and p73+ cells in the neocortical anlage, in the cortical hem, and in the septal,
      olfactory, and caudomedial telencephalic regions. The overall reduction in number
      of C-R cells in Lhx5 mutants is accompanied by formation of ectopic reelin+ cell
      clusters at the caudal telencephalon. Based on differential expression of
      molecular markers and by fluorescent cell tracing in cultured embryos, we located
      the origin of reelin+ ectopic cell clusters at the caudomedial telencephalic
      region. We also confirmed the existence of a normal migration stream of reelin+
      cells from the caudomedial area to telencephalic olfactory territories in wild
      type embryos. These results reveal a complex role for Lhx5 in regulating the
      development and normal distribution of C-R cells in the developing forebrain.

PMID- 20686000
TI  - In vivo activation of channelrhodopsin-2 reveals that normal patterns of
      spontaneous activity are required for motoneuron guidance and maintenance of
      guidance molecules.
AB  - Spontaneous, highly rhythmic episodes of propagating bursting activity are
      present early during the development of chick and mouse spinal cords.
      Acetylcholine, and GABA and glycine, which are both excitatory at this stage,
      provide the excitatory drive. It was previously shown that a moderate decrease in
      the frequency of bursting activity, caused by in ovo application of the GABA(A)
      receptor blocker, picrotoxin, resulted in motoneurons making dorsal-ventral (D-V)
      pathfinding errors in the limb and in the altered expression of guidance
      molecules associated with this decision. To distinguish whether the pathfinding
      errors were caused by perturbation of the normal frequency of bursting activity
      or interference with GABA(A) receptor signaling, chick embryos were chronically
      treated in ovo with picrotoxin to block GABA(A) receptors, while light activation
      by channelrhodopsin-2 was used to restore bursting activity to the control
      frequency. The restoration of normal patterns of neural activity in the presence
      of picrotoxin prevented the D-V pathfinding errors in the limb and maintained the
      normal expression levels of EphA4, EphB1, and polysialic acid on neural cell
      adhesion molecule, three molecules previously shown to be necessary for this
      pathfinding choice. These observations demonstrate that developing spinal motor
      circuits are highly sensitive to the precise frequency and pattern of spontaneous
      activity, and that any drugs that alter this activity could result in
      developmental defects.

PMID- 20686001
TI  - Persistent representation of juvenile experience in the adult songbird brain.
AB  - Juveniles sometimes learn behaviors that they cease to express as adults. Whether
      the adult brain retains a record of experiences associated with behaviors
      performed transiently during development remains unclear. We addressed this issue
      by studying neural representations of song in swamp sparrows, a species in which
      juveniles learn and practice many more songs than they retain in their adult
      vocal repertoire. We exposed juvenile swamp sparrows to a suite of tutor songs
      and confirmed that, although many tutor songs were imitated during development,
      not all copied songs were retained into adulthood. We then recorded
      extracellularly in the sensorimotor nucleus HVC in anesthetized sparrows to
      assess neuronal responsiveness to songs in the adult repertoire, tutor songs, and
      novel songs. Individual HVC neurons almost always responded to songs in the adult
      repertoire and commonly responded even more strongly to a tutor song. Effective
      tutor songs were not simply those that were acoustically similar to songs in the
      adult repertoire. Moreover, the strength of tutor song responses was unrelated to
      the number of times that the bird sang copies of those songs in juvenile or adult
      life. Notably, several neurons responded most strongly to a tutor song performed
      only rarely and transiently during juvenile life, or even to a tutor song for
      which we could find no evidence of ever having been copied. Thus, HVC neurons
      representing songs in the adult repertoire also appear to retain a lasting record
      of certain tutor songs, including those imitated only transiently.

PMID- 20686002
TI  - Technical communication: percutaneous radiofrequency mandibular nerve rhizotomy
      guided by high-speed real-time computed tomography fluoroscopy.
AB  - We present a new method of percutaneous radiofrequency mandibular nerve rhizotomy
      for pain relief in the mandibular region, in which needle placement is guided by
      high-speed real-time computed tomography (CT) fluoroscopy. Eleven patients (13
      procedures) with idiopathic trigeminal neuralgia underwent the procedure. CT
      fluoroscopy simultaneously provided 3 slices (1-mm interval series,
      craniocaudally) in 1 fluoroscopic view, allowing for accurate needle placement.
      Trigeminal neuralgia improved in all patients without severe complications. The
      mean numerical rating scales of pain intensity (+ or - sd) decreased from 6.5 (+
      or - 1.8, pretreatment) to 1.8 (+ or - 1.7, 1 month after treatment) and to 0.9
      (+ or - 1.0, 3 months after treatment). Our limited-case series suggests
      potential advantages for the new CT fluoroscopy guidance, but these findings
      await confirmation from randomized controlled trials and large-case series.

PMID- 20686003
TI  - A prospective evaluation of psoas muscle and intravascular injection in lumbar
      sympathetic ganglion block.
AB  - BACKGROUND: Intravascular and intramuscular injection of local anesthetics during
      lumbar sympathetic ganglion block (LSGB) can cause false positive or negative
      results in a diagnostic block, and complications. In the present study, we
      prospectively evaluated the incidence and possible factors causing intravascular
      and IM injection during LSGB. METHODS: We evaluated 216 LSGBs in 83 patients. All
      LSGBs were performed by 1 of the authors using a 3-needle technique. After final
      needle position was confirmed by biplanar fluoroscopy, an aspiration test was
      conducted, and 1 mL of contrast was injected sequentially. Incidences of psoas
      muscle injection, blood flashback, and the presence of intravascular contrast
      spread on static and real-time fluoroscopy were assessed. RESULTS: The incidence
      of psoas muscle injection of contrast was 21.3% (46/216), and it was associated
      with the level of injection (L2) significantly (chi(2) = 14.773, P = 0.001). The
      incidence of intravascular injection of contrast was 12.5% (27/216). Among 27
      cases of documented intravascular injections, 5.1% (11/216) of patients showed
      contrast spread at the area where the sympathetic ganglion was presumed to be and
      to the vessels simultaneously, and 7.4% (16/216) of patients showed only
      intravascular injection of contrast. The sensitivity of the aspiration test and
      static radiography were 40.7% and 70.4%, respectively. CONCLUSIONS: LSGB at the
      L2 level showed the lowest incidence of psoas muscle injection of contrast in
      comparison with LSGB at L3 and L4. The aspiration test and static radiography
      frequently missed the intravascular injection of contrast during LSGBs.

PMID- 20686004
TI  - The anticoagulant effect of protamine sulfate is attenuated in the presence of
      platelets or elevated factor VIII concentrations.
AB  - BACKGROUND: Protamine sulfate is the antidote for heparin, but in excess it
      exerts weak anticoagulation. METHODS: We evaluated the effects of increasing
      protamine concentrations (0 to 24 microg/mL) on prothrombin time and diluted
      Russell's viper venom time measurements on thrombin generation in platelet-poor
      and platelet-rich plasma after activation by tissue factor or actin, and on
      thromboelastometry in platelet-poor plasma and whole blood from 6 healthy
      volunteers. The reversibility of excess protamine (24 microg/mL) by recombinant
      factor VIIa or factor VIII/von Willebrand factor concentrate was also tested.
      RESULTS: Protamine prolonged prothrombin time and Russell's viper venom time,
      concentration dependently. Protamine also increased lag time and decreased peak
      of thrombin generation in platelet-poor plasma after tissue factor and actin
      activation. In platelet-rich plasma with platelets at 50 to 200 x 10(3)/microL,
      protamine (24 microg/mL) prolonged the lag time, but had no effect on peak
      thrombin generation. The addition of factor VIII/von Willebrand factor (1.5-3.0
      U/mL) to platelet-poor plasma with protamine (24 microg/mL) decreased lag time
      and increased peak thrombin generation with actin activation. A therapeutic
      concentration of recombinant factor VIIa (60 nM) only affected the lag time of
      thrombin generation triggered with actin. In agreement, protamine increased
      coagulation time evaluated by thromboelastometry significantly more in platelet
      poor plasma than in whole blood. CONCLUSIONS: We demonstrated that protamine
      affects the propagation of thrombin generation, which is partially reversed by
      platelets or increased factor VIII/von Willebrand factor concentrations. The
      present data suggest that excess protamine might potentially increase bleeding in
      the case of severe thrombocytopenia or low factor VIII.

PMID- 20686005
TI  - Local anesthetics depolarize mitochondrial membrane potential by intracellular
      alkalization in rat dorsal root ganglion neurons.
AB  - BACKGROUND: Although it has been reported that local anesthetics, especially
      lidocaine, are cytotoxic, the mechanism is unclear. Depolarization of the
      mitochondrial membrane potential (DeltaPsim), one of the markers of mitochondrial
      failure, is regulated by the proton electrochemical gradient (Delta H(+)).
      Therefore, intracellular pH ([pH]in) and mitochondrial pH ([pH]m) are important
      factors for modifying DeltaPsim. However, the effects of local anesthetics on
      [pH]in and [pH]m are unclear. To investigate mitochondrial responses to local
      anesthetics, we simultaneously measured [pH]m and [pH]in, along with DeltaPsim.
      METHODS: The ratiometric fluorescent probe JC-1 and HPTS were used for the
      simultaneous measurements of DeltaPsim with [pH]in in rat dorsal root ganglion
      neurons. A carboxy-SNARF-1 fluorescent probe was used to measure [pH]m.
      Lidocaine, mepivacaine, bupivacaine, procaine, QX-314, a charged form of
      lidocaine, and ammonium chloride (NH(4)Cl) were evaluated. RESULTS: DeltaPsim was
      depolarized and [pH]in was increased by lidocaine, mepivacaine, bupivacaine, and
      procaine in a dose-dependent manner. Significantly, a relationship between
      DeltaPsim and [pH]in was observed for lidocaine, mepivacaine, bupivacaine,
      procaine, and NH(4)Cl perfusion. In contrast, QX-314 did not change DeltaPsim or
      [pH]in. In low-pH saline (pH6) and in the presence of a weak acid, lidocaine
      failed to increase [pH]in or depolarize DeltaPsim. The [pH]m was also increased
      by lidocaine, mepivacaine, bupivacaine, procaine, and NH(4)Cl. CONCLUSION: These
      results demonstrate that uncharged (base) forms of local anesthetics induce
      DeltaPsim depolarization. One of the causes is intracellular and mitochondrial
      alkalization.

PMID- 20686006
TI  - Review article: the surgical approach to the management of increased intracranial
      pressure after traumatic brain injury.
AB  - Increased intracranial pressure occurring after severe traumatic brain injury is
      a common and potentially devastating phenomenon. It has been clearly demonstrated
      that increased intracranial pressure that is refractory to initial medical
      measures is a poor prognostic sign. Current optimal management is based on a
      sequential, target-driven approach combining both medical and surgical treatment
      strategies. The surgical measures in current common practice include external
      ventricular drain insertion and decompressive craniectomy. There is evidence that
      both of these measures reduce intracranial pressure but the effect on outcome,
      particularly in the long term, is equivocal. Current Brain Trauma Foundation
      guidelines recommend timely evacuation of mass lesions and there is clear
      guidance regarding the indications for intracranial pressure monitoring; however,
      decompressive craniectomy is only cautiously recommended as a possible option for
      selected patients. In this review, we highlight the ongoing debate about the use
      of decompressive craniectomy to control intracranial pressure after traumatic
      brain injury; included is a summary of review of the most recent literature on
      the effect of decompressive craniectomy on increased intracranial pressure after
      traumatic brain injury and associated long-term outcome. The RESCUEicp and DECRA
      studies are discussed in detail. It is hoped that these 2 randomized controlled
      trials, which are evaluating the short- and longer-term outcomes of decompressive
      craniectomy, will provide conclusive evidence regarding the role of decompressive
      craniectomy in managing increased intracranial pressure after trauma.

PMID- 20686007
TI  - Hand contamination of anesthesia providers is an important risk factor for
      intraoperative bacterial transmission.
AB  - BACKGROUND: We have recently shown that intraoperative bacterial transmission to
      patient IV stopcock sets is associated with increased patient mortality. In this
      study, we hypothesized that bacterial contamination of anesthesia provider hands
      before patient contact is a risk factor for direct intraoperative bacterial
      transmission. METHODS: Dartmouth-Hitchcock Medical Center is a tertiary care and
      level 1 trauma center with 400 inpatient beds and 28 operating suites. The first
      and second operative cases in each of 92 operating rooms were randomly selected
      for analysis. Eighty-two paired samples were analyzed. Ten pairs of cases were
      excluded because of broken or missing sampling protocol and lost samples. We
      identified cases of intraoperative bacterial transmission to the patient IV
      stopcock set and the anesthesia environment (adjustable pressure-limiting valve
      and agent dial) in each operating room pair by using a previously validated
      protocol. We then used biotype analysis to compare these transmitted organisms to
      those organisms isolated from the hands of anesthesia providers obtained before
      the start of each case. Provider-origin transmission was defined as potential
      pathogens isolated in the patient stopcock set or environment that had an
      identical biotype to the same organism isolated from hands of providers. We also
      assessed the efficacy of the current intraoperative cleaning protocol by
      evaluating isolated potential pathogens identified at the start of case 2. Poor
      intraoperative cleaning was defined as 1 or more potential pathogens found in the
      anesthesia environment at the start of case 2 that were not there at the
      beginning of case 1. We collected clinical and epidemiological data on all the
      cases to identify risk factors for contamination. RESULTS: One hundred sixty-four
      cases (82 case pairs) were studied. We identified intraoperative bacterial
      transmission to the IV stopcock set in 11.5 % (19/164) of cases, 47% (9/19) of
      which were of provider origin. We identified intraoperative bacterial
      transmission to the anesthesia environment in 89% (146/164) of cases, 12%
      (17/146) of which were of provider origin. The number of rooms that an attending
      anesthesiologist supervised simultaneously, the age of the patient, and patient
      discharge from the operating room to an intensive care unit were independent
      predictors of bacterial transmission events not directly linked to providers.
      CONCLUSION: The contaminated hands of anesthesia providers serve as a significant
      source of patient environmental and stopcock set contamination in the operating
      room. Additional sources of intraoperative bacterial transmission, including
      postoperative environmental cleaning practices, should be further studied.

PMID- 20686008
TI  - Brief reports: a clinical evaluation of block characteristics using one
      milliliter 2% lidocaine in ultrasound-guided axillary brachial plexus block.
AB  - We report onset and duration of ultrasound-guided axillary brachial plexus block
      using 1 mL of 2% lidocaine with 1:200,000 epinephrine per nerve (total local
      anesthetic volume 4 mL). Block performance time, block onset time, duration of
      surgery, and block duration were measured. Seventeen consecutive patients were
      recruited. The mean (SD) block performance and onset times were 271 (67.9)
      seconds and 9.7 (3.7) minutes, respectively. Block duration was 160.8 (30.7)
      minutes. All operations were performed using regional anesthesia alone. The
      duration of anesthesia obtained is sufficient for most ambulatory hand surgery.

PMID- 20686009
TI  - Lidocaine attenuates proinflammatory cytokine production induced by extracellular
      adenosine triphosphate in cultured rat microglia.
AB  - BACKGROUND: Our previous studies demonstrated that intrathecal lidocaine
      treatment could produce prolonged reversal of established hyperalgesia or
      allodynia, both induced by chronic constriction injury. Indeed, intrathecal
      lidocaine treatment remarkably suppressed the activation of p38 mitogen-activated
      protein kinase (MAPK) in hyperactive microglia. In the present study we suggest
      that lidocaine may act directly on the microglia and attenuate the release of
      cytokines. METHODS: We assessed the influence of lidocaine on the levels of
      phospho-p38 MAPK, tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL
      1beta), IL-6, and intracellular calcium triggered by extracellular adenosine
      triphosphate (ATP) in cultured rat microglia. Our experimental methods included
      Western blot, real-time reverse transcription-polymerase chain reaction, enzyme
      linked immunosorbent assay, and calcium imaging. RESULTS: We found that lidocaine
      (in a dose-dependent manner) significantly attenuated p38 MAPK activation
      triggered by 1 mM ATP, by inhibiting the transcription of 3 cytokine messenger
      RNAs and causing a decrease in their respective protein concentrations (TNF
      alpha, IL-1beta, and IL-6, P < 0.05, vs. the ATP group). SB203580, an antagonist
      of P38, attenuated ATP-activated elevation in protein levels of TNF-alpha, IL
      1beta, and IL-6 in the microglia. The high level of intracellular calcium
      ([Ca(2+)]i) that is induced by ATP was decreased by the addition of 10 mM
      lidocaine (P < 0.05 vs. the ATP group). CONCLUSIONS: These findings indicate that
      lidocaine can directly act on microglia. Lidocaine, by inhibiting the increase of
      intracellular calcium, also inhibited p38 MAPK activation and attenuated the
      production of proinflammatory cytokines (including TNF-alpha, IL-1beta, and IL
      6), which were triggered by extracellular ATP in cultured rat microglia.

PMID- 20686010
TI  - Case report: a thrombus in the venous reservoir while using bivalirudin in a
      patient with heparin-induced thrombocytopenia undergoing heart transplantation.
AB  - Direct thrombin inhibitors are heparin alternatives for anticoagulation during
      cardiopulmonary bypass in patients with heparin-induced thrombocytopenia. We
      report a case of a large thrombus forming in the venous reservoir while using
      bivalirudin. We suggest that blood stasis associated with the full venous
      reservoir maintained in this case led to formation of a large thrombus at the top
      of the venous canister. Furthermore, activated clotting times may not accurately
      reflect the magnitude of anticoagulation when using direct thrombin inhibitors.

PMID- 20686011
TI  - Presenting research risks and benefits to parents: does format matter?
AB  - BACKGROUND: Several studies suggest that many parents and research participants
      have poor understanding of the elements of consent, particularly the risks and
      benefits. However, some data suggest that the format and framing of research
      risks and benefits may be an important determinant of subject understanding. We
      examined the effect of tabular and graphical presentation of risks and benefits
      on parents' understanding of a research study. METHODS: Parents of children
      scheduled to undergo an elective surgical procedure (n = 408) were randomized to
      receive information about the risks and benefits of a sham study of postoperative
      pain control using text, tables, or pictographs and then completed a
      questionnaire to examine their gist (essential) and verbatim (actual)
      understanding of the information. Parent demographics were recorded and their
      literacy and numeracy skills measured. RESULTS: Parents randomized to receive
      information using tables or pictographs had significantly (P < 0.025) greater
      gist and verbatim understanding than did parents who received the information
      using standard text. Tables and pictographs were also superior to text in
      promoting understanding among parents with low numeracy and literacy skills.
      CONCLUSIONS: Many parents and patients have difficulty in assimilating and
      interpreting risk/benefit information for both research and treatment. This is
      due, in part, to the manner in which risks and benefits are communicated and to
      the literacy and numeracy abilities of the individual. The results of this study
      suggest a simple and practical method for enhancing understanding of risk/benefit
      statistics for parents with varying numeracy and literacy skills.

PMID- 20686012
TI  - Positional blood pressure change and the risk of hypotension during spinal
      anesthesia for cesarean delivery: an observational study.
AB  - BACKGROUND: We investigated whether preoperative positional arterial blood
      pressure change predicted hypotension and ephedrine requirement during spinal
      anesthesia for cesarean delivery. METHODS: Arterial blood pressure was measured
      in 66 women undergoing cesarean delivery in the supine and the right lateral
      positions. Positional blood pressure change was defined as the difference between
      mean blood pressure in the right lateral and supine positions. Hypotension (<80%
      baseline) was recorded, and severe hypotension (<70% baseline) was treated with
      ephedrine. RESULTS: The mean (range) positional blood pressure change was 11 (3
      29) mm Hg, and the incidence of hypotension was 41%. Positional blood pressure
      change and heart rate correlated with hypotension (P < 0.001 for both) and
      ephedrine requirement (P = 0.004). Positional blood pressure change in those who
      developed hypotension was higher than for those without hypotension (mean (SD),
      17 (6) vs. 7 (2) mm Hg, P < 0.001). CONCLUSIONS: A preoperative increase in blood
      pressure after position change may be a good variable to predict hypotension
      during spinal anesthesia for cesarean delivery.

PMID- 20686013
TI  - A prospective clinical registry of ultrasound-guided regional anesthesia for
      ambulatory shoulder surgery.
AB  - BACKGROUND: There is a lack of clinical registries to document efficacy and
      safety of ultrasound-guided regional anesthesia. Interscalene blocks are
      effective for shoulder arthroscopy, and ultrasound guidance may reduce risk.
      Furthermore, ultrasound-guided supraclavicular block is a novel approach for
      shoulder anesthesia that may have less risk for neurological symptoms than
      interscalene block. METHODS: One thousand one hundred sixty-nine patients
      undergoing ultrasound-guided regional anesthesia for ambulatory shoulder
      arthroscopy were enrolled in our prospective registry. Standardized perioperative
      data were collected including a preoperative neurological screening tool. Either
      interscalene or supraclavicular block was performed at the discretion of the
      clinical team. Standardized follow-up was performed in the postanesthesia care
      unit and at 1 week. Postoperative neurological symptoms (PONS) were assessed at
      the 1-week follow-up with the same screening tool by a blinded neurologist.
      RESULTS: Ultrasound-guided interscalene (n = 515) and supraclavicular (n = 654)
      blocks had excellent anesthetic success (99.8%; 95% confidence interval [CI],
      99.4%-99.9%) with 0% (95% CI, 0%-0.3%) incidence of vascular puncture or
      intravascular injection. The incidence of hoarseness in the postanesthesia care
      unit was significantly less with supraclavicular (22% with 95% CI, 19%-26%) than
      interscalene block (31% with 95% CI, 27%-35%). The incidence of dyspnea was
      similar (7% for supraclavicular vs 10% with interscalene). No patient had a
      clinically apparent pneumothorax. The incidence of PONS was very low (0.4% with
      95% CI, 0.1%-1%), and there was a 0% (95% CI, 0%-0.3%) incidence of permanent
      nerve injury. CONCLUSIONS: Ultrasound-guided interscalene and supraclavicular
      blocks are effective and safe for shoulder arthroscopy. Temporary and permanent
      PONS is uncommon.

PMID- 20686014
TI  - Brief-reports: elevated myostatin levels in patients with liver disease: a
      potential contributor to skeletal muscle wasting.
AB  - Loss of skeletal muscle mass is a poorly understood complication of end-stage
      liver disease (ESLD). Based on recent stem cell literature, we hypothesized that
      the potent negative regulator of muscle mass, myostatin, could play a role in the
      muscle loss associated with ESLD. In this preliminary investigation, we measured
      myostatin levels in patients undergoing liver transplant evaluation, using a
      novel enzyme-linked immunosensitivity assay. Myostatin levels were significantly
      elevated in patients with ESLD compared with healthy controls. These data suggest
      that myostatin deserves further investigation as a target for therapies designed
      to preserve muscle mass in patients with ESLD.

PMID- 20686015
TI  - Simian immunodeficiency virus-specific CD8+ T cells recognize Vpr- and Rev
      derived epitopes early after infection.
AB  - The kinetics of CD8(+) T cell epitope presentation contribute to the antiviral
      efficacy of these cells yet remain poorly defined. Here, we demonstrate
      presentation of virion-derived Vpr peptide epitopes early after viral penetration
      and prior to presentation of Vif-derived epitopes, which required de novo Vif
      synthesis. Two Rev epitopes exhibited differential presentation kinetics, with
      one Rev epitope presented within 1 h of infection. We also demonstrate that
      cytolytic activity mirrors the recognition kinetics of infected cells. These
      studies show for the first time that Vpr- and Rev-specific CD8(+) T cells
      recognize and kill simian immunodeficiency virus (SIV)-infected CD4(+) T cells
      early after SIV infection.

PMID- 20686017
TI  - Genome-wide detection and characterization of endogenous retroviruses in Bos
      taurus.
AB  - Endogenous retroviruses (ERVs) are the proviral phase of exogenous retroviruses
      that become integrated into a host germ line. They can play an important role in
      the host genome. Bioinformatic tools have been used to detect ERVs in several
      vertebrates, primarily primates and rodents. Less information is available
      regarding ERVs in other mammalian groups, and the source of this information is
      basically experimental. We analyzed the genome of the cow (Bos taurus) using
      three different methods. A BLAST-based method detected 928 possible ERVs,
      LTR_STRUC detected 4,487 elements flanked by long terminal repeats (LTRs), and
      Retrotector detected 9,698 ERVs. The ERVs were not homogeneously distributed
      across chromosomes; the number of ERVs was positively correlated with chromosomal
      size and negatively correlated with chromosomal GC content. The bovine ERVs
      (BoERVs) were classified into 24 putative families, with 20 of them not
      previously described. One of these new families, BoERV1, was the most abundant
      family and appeared to be specific to ruminants. An analysis of representatives
      of ERV families from rodents, primates, and ruminants showed a phylogenetic
      relationship following their hosts' relationships. This study demonstrates the
      importance of using multiple methods when trying to identify new ERVs and shows
      that the number of bovine ERV families is not as limited as previously thought.

PMID- 20686016
TI  - Low-dose mucosal simian immunodeficiency virus infection restricts early
      replication kinetics and transmitted virus variants in rhesus monkeys.
AB  - Defining the earliest virologic events following human immunodeficiency virus
      type 1 (HIV-1) transmission may be critical for the design of vaccine strategies
      aimed at blocking acquisition of HIV-1 infection. In particular, the length of
      the eclipse phase and the number of transmitted virus variants may define the
      window in which a prophylactic vaccine must act. Here we show that the dose of
      the virus inoculum affects these key virologic parameters following intrarectal
      simian immunodeficiency virus (SIV) infection of rhesus monkeys. Low-dose SIV
      infection resulted in a lengthened eclipse phase, fewer transmitted virus
      variants, and decreased innate immune activation compared with these parameters
      in high-dose SIV infection. These data suggest a mechanism by which it may be
      considerably easier for a vaccine to protect against low-risk HIV-1 transmission
      than against high-risk HIV-1 transmission. These findings have implications for
      the design and interpretation of HIV-1 vaccine efficacy studies.

PMID- 20686018
TI  - A single-amino-acid substitution in herpes simplex virus 1 envelope glycoprotein
      B at a site required for binding to the paired immunoglobulin-like type 2
      receptor alpha (PILRalpha) abrogates PILRalpha-dependent viral entry and reduces
      pathogenesis.
AB  - Paired immunoglobulin-like type 2 receptor alpha (PILRalpha) is a herpes simplex
      virus 1 (HSV-1) entry receptor that associates with O-glycans on HSV-1 envelope
      glycoprotein B (gB). Two threonine residues (Thr-53 and Thr-480) in gB, which are
      required for the addition of the principal gB O-glycans, are essential for
      binding to soluble PILRalpha. However, the role of the two threonines in
      PILRalpha-dependent viral entry remains to be elucidated. Therefore, we
      constructed a recombinant HSV-1 carrying an alanine replacement of gB Thr-53
      alone (gB-T53A) or of both gB Thr-53 and Thr-480 (gB-T53/480A) and demonstrated
      that these mutations abrogated viral entry in CHO cells expressing PILRalpha. In
      contrast, the mutations had no effect on viral entry in CHO cells expressing
      known host cell receptors for HSV-1 gD, viral entry in HL60 cells expressing
      myelin-associated glycoprotein (MAG) (another HSV-1 gB receptor), viral
      attachment to heparan sulfate, and viral replication in PILRalpha-negative cells.
      These results support the hypothesis that gB Thr-53 and Thr-480 as well as gB O
      glycosylation, probably at these sites, are critical for PILRalpha-dependent
      viral entry. Interestingly, following corneal inoculation in mice, the gB-T53A
      and gB-T53/480A mutations significantly reduced viral replication in the cornea,
      the development of herpes stroma keratitis, and neuroinvasiveness. The abilities
      of HSV-1 to enter cells in a PILRalpha-dependent manner and to acquire specific
      carbohydrates on gB are therefore linked to an increase in viral replication and
      virulence in the experimental murine model.

PMID- 20686019
TI  - The endoplasmic reticulum provides the membrane platform for biogenesis of the
      flavivirus replication complex.
AB  - The cytoplasmic replication of positive-sense RNA viruses is associated with a
      dramatic rearrangement of host cellular membranes. These virus-induced changes
      result in the induction of vesicular structures that envelop the virus
      replication complex (RC). In this study, we have extended our previous
      observations on the intracellular location of West Nile virus strain Kunjin virus
      (WNV(KUN)) to show that the virus-induced recruitment of host proteins and
      membrane appears to occur at a pre-Golgi step. To visualize the WNV(KUN)
      replication complex, we performed three-dimensional (3D) modeling on tomograms
      from WNV(KUN) replicon-transfected cells. These analyses have provided a 3D
      representation of the replication complex, revealing the open access of the
      replication complex with the cytoplasm and the fluidity of the complex to the
      rough endoplasmic reticulum. In addition, we provide data that indicate that a
      majority of the viral RNA species housed within the RC is in a double-stranded
      RNA (dsRNA) form.

PMID- 20686020
TI  - Recombinant soluble, multimeric HA and NA exhibit distinctive types of protection
      against pandemic swine-origin 2009 A(H1N1) influenza virus infection in ferrets.
AB  - The emergence and subsequent swift and global spread of the swine-origin
      influenza virus A(H1N1) in 2009 once again emphasizes the strong need for
      effective vaccines that can be developed rapidly and applied safely. With this
      aim, we produced soluble, multimeric forms of the 2009 A(H1N1) HA (sHA(3)) and NA
      (sNA(4)) surface glycoproteins using a virus-free mammalian expression system and
      evaluated their efficacy as vaccines in ferrets. Immunization twice with 3.75
      microg doses of these antigens elicited strong antibody responses, which were
      adjuvant dependent. Interestingly, coadministration of both antigens strongly
      enhanced the HA-specific but not the NA-specific responses. Distinct patterns of
      protection were observed upon challenge inoculation with the homologous H1N1
      virus. Whereas vaccination with sHA(3) dramatically reduced virus replication
      (e.g., by lowering pulmonary titers by about 5 log(10) units), immunization with
      sNA(4) markedly decreased the clinical effects of infection, such as body weight
      loss and lung pathology. Clearly, optimal protection was achieved by the
      combination of the two antigens. Our observations demonstrate the great vaccine
      potential of multimeric HA and NA ectodomains, as these can be easily, rapidly,
      flexibly, and safely produced in high quantities. In particular, our study
      underscores the underrated importance of NA in influenza vaccination, which we
      found to profoundly and specifically contribute to protection by HA. Its
      inclusion in a vaccine is likely to reduce the HA dose required and to broaden
      the protective immunity.

PMID- 20686021
TI  - A gC1qR prevents white spot syndrome virus replication in the freshwater crayfish
      Pacifastacus leniusculus.
AB  - The gC1qR/p32 protein is a multiple receptor for several proteins and pathogens.
      We cloned a gC1qR homologue in a crustacean, Pacifastacus leniusculus, and
      analyzed the expression of P. leniusculus C1qR (PlgC1qR) in various tissues. The
      gC1qR/p32 transcript was significantly enhanced by white spot syndrome virus
      (WSSV) infection 6 h after viral infection both in vitro in a hematopoietic
      tissue cell culture (Hpt) and in vivo compared to appropriate controls. Moreover,
      PlgC1qR silencing in both the Hpt cell culture and live crayfish enhanced the
      WSSV replication. In addition, by making a recombinant PlgC1qR protein we could
      show that if this recombinant protein was injected in a crayfish, Pacifastacus
      leniusculus, followed by injection of WSSV, this significantly reduced viral
      replication in vivo. Furthermore, if the recombinant PlgC1qR was incubated with
      Hpt cells and then WSSV was added, this also reduced viral replication. These
      experiments clearly demonstrate that recombinant PlgC1qR reduce WSSV replication
      both in vivo and in vitro. The results from a far-Western overlay and glutathione
      S-transferase pull-down assays showed that PlgC1qR could bind to VP15, VP26, and
      VP28. Altogether, these results demonstrate a role for PlgC1qR in antiviral
      activity against WSSV.

PMID- 20686022
TI  - Mononucleosis and antigen-driven T cell responses have different requirements for
      interleukin-2 signaling in murine gammaherpesvirus infection.
AB  - Interleukin-2 (IL-2) has been implicated as being necessary for the optimal
      formation of primary CD8(+) T cell responses against various pathogens. Here we
      have examined the role that IL-2 signaling plays in several aspects of a CD8(+) T
      cell response against murine gammaherpesvirus 68 (MHV-68). Exposure to MHV-68
      causes a persistent infection, along with infectious mononucleosis, providing a
      model for studying these processes in mice. Our study indicates that CD25 is
      necessary for optimal expansion of the antigen-specific CD8(+) T cell response
      but not for the long-term memory response. Contrastingly, IL-2 signaling through
      CD25 is absolutely required for CD8(+) T cell mononucleosis.

PMID- 20686023
TI  - Mucosal trafficking of vector-specific CD4+ T lymphocytes following vaccination
      of rhesus monkeys with adenovirus serotype 5.
AB  - Post hoc analysis of the phase 2b Step study evaluating a recombinant adenovirus
      serotype 5 (rAd5)-based HIV-1 vaccine candidate suggested a potential increased
      risk of HIV-1 acquisition in subjects who were baseline Ad5 seropositive and
      uncircumcised. These concerns had a profound impact on the HIV-1 vaccine
      development field, although the mechanism underlying this observation remains
      unknown. It has been hypothesized that rAd5 vaccination of baseline Ad5
      seropositive individuals may have resulted in anamnestic, vector-specific CD4(+)
      T lymphocytes that could have trafficked to mucosal sites and served as increased
      targets for HIV-1 infection. Here we show that Ad5-specific CD4(+) T lymphocyte
      responses at mucosal sites following rAd5-Gag/Pol/Nef vaccination were comparable
      in rhesus monkeys with and without baseline Ad5 immunity. Moreover, the total
      cellular inflammatory infiltrates and the CD3(+), CD4(+), HLA-DR(+), Ki67(+), and
      langerin(+) cellular subpopulations in colorectal and foreskin mucosa were
      similar in both groups. Thus, no greater trafficking of Ad5-specific CD4(+) T
      lymphocytes to mucosal target sites was observed following rAd5 vaccination of
      rhesus monkeys with baseline Ad5 immunity. These findings from this nonhuman
      primate model provide evidence against the hypothesis that recruitment of vector
      specific target cells to mucosal sites led to increased HIV-1 acquisition in Ad5
      seropositive, uncircumcised vaccinees in the Step study.

PMID- 20686024
TI  - The human papillomavirus type 16 E5 oncoprotein inhibits epidermal growth factor
      trafficking independently of endosome acidification.
AB  - The human papillomavirus type 16 E5 oncoprotein (16E5) enhances acute, ligand
      dependent activation of the epidermal growth factor receptor (EGFR) and
      concomitantly alkalinizes endosomes, presumably by binding to the 16-kDa "c"
      subunit of the V-ATPase proton pump (16K) and inhibiting V-ATPase function.
      However, the relationship between 16K binding, endosome alkalinization, and
      altered EGFR signaling remains unclear. Using an antibody that we generated
      against 16K, we found that 16E5 associated with only a small fraction of
      endogenous 16K in keratinocytes, suggesting that it was unlikely that E5 could
      significantly affect V-ATPase function by direct inhibition. Nevertheless, E5
      inhibited the acidification of endosomes, as determined by a new assay using a
      biologically active, pH-sensitive fluorescent EGF conjugate. Since we also found
      that 16E5 did not alter cell surface EGF binding, the number of EGFRs on the cell
      surface, or the endocytosis of prebound EGF, we postulated that it might be
      blocking the fusion of early endosomes with acidified vesicles. Our studies with
      pH-sensitive and -insensitive fluorescent EGF conjugates and fluorescent dextran
      confirmed that E5 prevented endosome maturation (acidification and enlargement)
      by inhibiting endosome fusion. The E5-dependent defect in vesicle fusion was not
      due to detectable disruption of actin, tubulin, vimentin, or cytokeratin
      filaments, suggesting that membrane fusion was being directly affected rather
      than vesicle transport. Perhaps most importantly, while bafilomycin A(1) (like
      E5) binds to 16K and inhibits endosome acidification, it did not mimic the
      ability of E5 to inhibit endosome enlargement or the trafficking of EGF. Thus,
      16E5 alters EGF endocytic trafficking via a pH-independent inhibition of vesicle
      fusion.

PMID- 20686025
TI  - Crystallographic structure of porcine adenovirus type 4 fiber head and galectin
      domains.
AB  - Adenovirus isolate NADC-1, a strain of porcine adenovirus type 4, has a fiber
      containing an N-terminal virus attachment region, shaft and head domains, and a C
      terminal galectin domain connected to the head by an RGD-containing sequence. The
      crystal structure of the head domain is similar to previously solved adenovirus
      fiber head domains, but specific residues for binding the coxsackievirus and
      adenovirus receptor (CAR), CD46, or sialic acid are not conserved. The structure
      of the galectin domain reveals an interaction interface between its two
      carbohydrate recognition domains, locating both sugar binding sites face to face.
      Sequence evidence suggests other tandem-repeat galectins have the same
      arrangement. We show that the galectin domain binds carbohydrates containing
      lactose and N-acetyl-lactosamine units, and we present structures of the galectin
      domain with lactose, N-acetyl-lactosamine, 3-aminopropyl-lacto-N-neotetraose, and
      2-aminoethyl-tri(N-acetyl-lactosamine), confirming the domain as a bona fide
      galectin domain.

PMID- 20686026
TI  - Simian virus 40 activates ATR-Delta p53 signaling to override cell cycle and DNA
      replication control.
AB  - During infection, simian virus 40 (SV40) attempts to take hold of the cell, while
      the host responds with various defense systems, including the ataxia
      telangiectasia mutated/ATM-Rad3 related (ATM/ATR)-mediated DNA damage response
      pathways. Here we show that upon viral infection, ATR directly activates the p53
      isoform Deltap53, leading to upregulation of the Cdk inhibitor p21 and
      downregulation of cyclin A-Cdk2/1 (AK) activity, which force the host to stay in
      the replicative S phase. Moreover, downregulation of AK activity is a
      prerequisite for the generation of hypophosphorylated, origin-competent DNA
      polymerase alpha-primase (hypo-Polalpha), which is, unlike AK-phosphorylated
      Polalpha (P-Polalpha), recruited by SV40 large T antigen (T-Ag) to initiate viral
      DNA replication. Prevention of the downregulation of AK activity by inactivation
      of ATR-Deltap53-p21 signaling significantly reduced the T-Ag-interacting hypo
      Polalpha population and, accordingly, SV40 replication efficiency. Moreover, the
      ATR-Deltap53 pathway facilitates the proteasomal degradation of the 180-kDa
      catalytic subunit of the non-T-Ag-interacting P-Polalpha, giving rise to T-Ag
      interacting hypo-Polalpha. Thus, the purpose of activating the ATR-Deltap53-p21
      mediated intra-S checkpoint is to maintain the host in S phase, an optimal
      environment for SV40 replication, and to modulate the host DNA replicase, which
      is indispensable for viral amplification.

PMID- 20686027
TI  - Long-term restriction by APOBEC3F selects human immunodeficiency virus type 1
      variants with restored Vif function.
AB  - Tandem stop mutations K26X and H27X in human immunodeficiency virus type 1 (HIV
      1) vif compromise virus replication in human T-cell lines that stably express
      APOBEC3F (A3F) or APOBEC3G (A3G). We previously reported that partial resistance
      to A3G could develop in these Vif-deficient viruses through a nucleotide A200-to
      T/C transversion and a vpr null mutation, but these isolates were still
      susceptible to restriction by A3F. Here, long-term selection experiments were
      done to determine how these A3G-selected isolates might evolve to spread in the
      presence of A3F. We found that A3F, like A3G, is capable of potent, long-term
      restriction that eventually selects for heritable resistance. In all 7 instances,
      the selected isolates had restored Vif function to cope with A3F activity. In two
      isolates, Vif Q26-Q27 and Y26-Q27, the resistance phenotype recapitulated in
      molecular clones, but when the selected vif alleles were analyzed in the context
      of an otherwise wild-type viral background, a different outcome emerged. Although
      HIV-1 clones with Vif Q26-Q27 or Y26-Q27 were fully capable of overcoming A3F,
      they were now susceptible to restriction by A3G. Concordant with prior studies, a
      lysine at position 26 proved essential for A3G neutralization. These data combine
      to indicate that A3F and A3G exert at least partly distinct selective pressures
      and that Vif function may be essential for the virus to replicate in the presence
      of A3F.

PMID- 20686028
TI  - Nuclear localization of tegument-delivered pp71 in human cytomegalovirus-infected
      cells is facilitated by one or more factors present in terminally differentiated
      fibroblasts.
AB  - Herpesviral virions contain a tegument layer that consists primarily of viral
      proteins. The delivery of fully functional proteins to infected cells upon virion
      envelope fusion to the plasma membrane allows herpesviruses to modulate cellular
      activities prior to viral gene expression. Certain tegument proteins can also
      regulate viral processes. For example, the pp71 tegument protein encoded by the
      UL82 gene of human cytomegalovirus (HCMV) stimulates viral immediate early (IE)
      gene expression and thus acts to initiate the productive lytic infectious cycle.
      In terminally differentiated fibroblasts infected with HCMV, tegument-delivered
      pp71 traffics to the nucleus and degrades the cellular transcriptional
      corepressor Daxx to initiate viral IE gene expression and lytic replication.
      However, when HCMV infects incompletely differentiated cells, tegument-delivered
      pp71 remains in the cytoplasm, allowing the nucleus-localized Daxx protein to
      silence viral IE gene expression and promote the establishment of a latent
      infection in certain cell types. We sought to determine whether undifferentiated
      cells block the trafficking of tegument-delivered pp71 to the nucleus or whether
      differentiated cells facilitate the nuclear transport of tegument-delivered pp71.
      Heterogenous cell fusion experiments demonstrated that tegument-delivered pp71
      found in the cytoplasm of undifferentiated NT2 cells could be driven into the
      nucleus by one or more factors provided by fully differentiated fibroblasts. Our
      data raise the intriguing possibility that latency is the default program
      launched by HCMV upon viral entry into cells and that lytic infection is
      initiated only in certain (differentiated) cells that can facilitate the delivery
      of incoming pp71 to the nucleus.

PMID- 20686029
TI  - Chromosomal integration of adenoviral vector DNA in vivo.
AB  - So far there has been no report of any clinical or preclinical evidence for
      chromosomal vector integration following adenovirus (Ad) vector-mediated gene
      transfer in vivo. We used liver gene transfer with high-capacity Ad vectors in
      the FAH(Deltaexon5) mouse model to analyze homologous and heterologous
      recombination events between vector and chromosomal DNA. Intravenous injection of
      Ad vectors either expressing a fumarylacetoacetate hydrolase (FAH) cDNA or
      carrying part of the FAH genomic locus resulted in liver nodules of FAH
      expressing hepatocytes, demonstrating chromosomal vector integration. Analysis of
      junctions between vector and chromosomal DNA following heterologous recombination
      indicated integration of the vector genome through its termini. Heterologous
      recombination occurred with a median frequency of 6.72 x 10(-5) per transduced
      hepatocyte, while homologous recombination occurred more rarely with a median
      frequency of 3.88 x 10(-7). This study has established quantitative and
      qualitative data on recombination of adenoviral vector DNA with genomic DNA in
      vivo, contributing to a risk-benefit assessment of the biosafety of Ad vector
      mediated gene transfer.

PMID- 20686030
TI  - Inactivation and disassembly of the anaphase-promoting complex during human
      cytomegalovirus infection is associated with degradation of the APC5 and APC4
      subunits and does not require UL97-mediated phosphorylation of Cdh1.
AB  - Infection of quiescent cells by human cytomegalovirus (HCMV) elicits severe cell
      cycle deregulation, resulting in a G(1)/S arrest, which can be partly attributed
      to the inactivation of the anaphase-promoting complex (APC). As we previously
      reported, the premature phosphorylation of its coactivator Cdh1 and/or the
      dissociation of the core complex can account for the inactivation. We have
      expanded on these results and further delineated the key components required for
      disabling the APC during HCMV infection. The viral protein kinase UL97 was
      hypothesized to phosphorylate Cdh1, and consistent with this, phosphatase assays
      utilizing a virus with a UL97 deletion mutation (DeltaUL97 virus) indicated that
      Cdh1 is hypophosphorylated at early times in the infection. Mass spectrometry
      analysis demonstrated that UL97 can phosphorylate Cdh1 in vitro, and the majority
      of the sites identified correlated with previously characterized cyclin-dependent
      kinase (Cdk) consensus sites. Analysis of the APC core complex during DeltaUL97
      virus infection showed APC dissociation occurring at the same time as during
      infection with wild-type virus, suggesting that the UL97-mediated phosphorylation
      of Cdh1 is not required for this to occur. Further investigation of the APC
      subunits showed a proteasome-dependent loss of the APC5 and APC4 subunits that
      was temporally associated with the disassembly of the APC. Immediate early viral
      gene expression was not sufficient for the degradation of APC4 and APC5,
      indicating that a viral early gene product(s), possibly in association with a de
      novo-synthesized cellular protein(s), is involved.

PMID- 20686031
TI  - Basic residues within the ebolavirus VP35 protein are required for its viral
      polymerase cofactor function.
AB  - The ebolavirus (EBOV) VP35 protein binds to double-stranded RNA (dsRNA), inhibits
      host alpha/beta interferon (IFN-alpha/beta) production, and is an essential
      component of the viral polymerase complex. Structural studies of the VP35 C
      terminal IFN inhibitory domain (IID) identified specific structural features,
      including a central basic patch and a hydrophobic pocket, that are important for
      dsRNA binding and IFN inhibition. Several other conserved basic residues
      bordering the central basic patch and a separate cluster of basic residues,
      called the first basic patch, were also identified. Functional analysis of
      alanine substitution mutants indicates that basic residues outside the central
      basic patch are not required for dsRNA binding or for IFN inhibition. However,
      minigenome assays, which assess viral RNA polymerase complex function, identified
      these other basic residues to be critical for viral RNA synthesis. Of these, a
      subset located within the first basic patch is important for VP35-nucleoprotein
      (NP) interaction, as evidenced by the inability of alanine substitution mutants
      to coimmunoprecipitate with NP. Therefore, first basic patch residues are likely
      critical for replication complex formation through interactions with NP.
      Coimmunoprecipitation studies further demonstrate that the VP35 IID is sufficient
      to interact with NP and that dsRNA can modulate VP35 IID interactions with NP.
      Other basic residue mutations that disrupt the VP35 polymerase cofactor function
      do not affect interaction with NP or with the amino terminus of the viral
      polymerase. Collectively, these results highlight the importance of conserved
      basic residues from the EBOV VP35 C-terminal IID and validate the VP35 IID as a
      potential therapeutic target.

PMID- 20686032
TI  - The viral latency-associated nuclear antigen augments the B-cell response to
      antigen in vivo.
AB  - Gammaherpesviruses, including Kaposi sarcoma-associated herpesvirus (KSHV),
      establish latency in B cells. We hypothesized that the KSHV latency-associated
      nuclear antigen (LANA/orf73) provides a selective advantage to infected B cells
      by driving proliferation in response to antigen. To test this, we used LANA B
      cell transgenic mice. Eight days after immunization with antigen without
      adjuvant, LANA mice had significantly more activated germinal center (GC) B cells
      (CD19(+) PNA(+) CD71(+)) than controls. This was dependent upon B-cell receptor
      since LANA did not restore the GC defect of CD19 knockout mice. However, LANA was
      able to restore the marginal zone defect in CD19 knockout mice.

PMID- 20686033
TI  - Ultrastructural and biophysical characterization of hepatitis C virus particles
      produced in cell culture.
AB  - We analyzed the biochemical and ultrastructural properties of hepatitis C virus
      (HCV) particles produced in cell culture. Negative-stain electron microscopy
      revealed that the particles were spherical (~40- to 75-nm diameter) and
      pleomorphic and that some of them contain HCV E2 protein and apolipoprotein E on
      their surfaces. Electron cryomicroscopy revealed two major particle populations
      of ~60 and ~45 nm in diameter. The ~60-nm particles were characterized by a
      membrane bilayer (presumably an envelope) that is spatially separated from an
      internal structure (presumably a capsid), and they were enriched in fractions
      that displayed a high infectivity-to-HCV RNA ratio. The ~45-nm particles lacked a
      membrane bilayer and displayed a higher buoyant density and a lower infectivity
      to-HCV RNA ratio. We also observed a minor population of very-low-density, >100
      nm-diameter vesicular particles that resemble exosomes. This study provides low
      resolution ultrastructural information of particle populations displaying
      differential biophysical properties and specific infectivity. Correlative
      analysis of the abundance of the different particle populations with infectivity,
      HCV RNA, and viral antigens suggests that infectious particles are likely to be
      present in the large ~60-nm HCV particle populations displaying a visible
      bilayer. Our study constitutes an initial approach toward understanding the
      structural characteristics of infectious HCV particles.

PMID- 20686034
TI  - Herpes simplex virus immediate-early ICP0 protein inhibits Toll-like receptor 2
      dependent inflammatory responses and NF-kappaB signaling.
AB  - The discovery of the Toll-like receptors (TLRs) and their importance in the
      regulation of host responses to infection raised attention to the complex
      interplay between viral gene products and the host innate immune responses in
      determining the outcome of virus infection. Robust inflammatory cytokine
      responses are observed in herpes simplex virus (HSV)-infected animals and cells.
      Our studies have demonstrated that Toll-like receptor 2 (TLR2) activation by HSV
      results in NF-kappaB activation with concomitant inflammatory cytokine production
      and that TLR2 activation plays a critical role in HSV-induced pathology and
      mortality. Here we demonstrate that the HSV-1 immediate-early ICP0 protein
      reduces the TLR2-mediated inflammatory response to HSV 1 (HSV-1) infection.
      Expression of ICP0 alone is sufficient to block TLR2-driven responses to both
      viral and nonviral ligands at or downstream of the MyD88 adaptor and upstream of
      p65. ICP0 alone can also reduce the levels of MyD88 and Mal (TIRAP). In HSV
      infected cells, the E3 ligase function of ICP0 and cellular proteasomal activity
      are required for the inhibitory activity. Our results argue for a model in which
      ICP0 promotes the degradation of TLR adaptor molecules and inhibition of the
      inflammatory response, much as it inhibits the interferon response by
      sequestration and degradation of interferon regulatory factor 3 (IRF-3).

PMID- 20686035
TI  - Adenovirus-based vaccines: comparison of vectors from three species of
      adenoviridae.
AB  - In order to better understand the broad applicability of adenovirus (Ad) as a
      vector for human vaccine studies, we compared four adenovirus (Ad) vectors from
      families C (Ad human serotype 5 [HAdV-5; here referred to as AdHu5]), D (HAdV-26;
      here referred to as AdHu26), and E (simian serotypes SAdV-23 and SAdV-24; here
      referred to as chimpanzee serotypes 6 and 7 [AdC6 and AdC7, respectively]) of the
      Adenoviridae. Seroprevalence rates and titers of neutralizing antibodies to the
      two human-origin Ads were found to be higher than those reported previously,
      especially in countries of sub-Saharan Africa. Conversely, prevalence rates and
      titers to AdC6 and AdC7 were markedly lower. Healthy human adults from the United
      States had readily detectable circulating T cells recognizing Ad viruses, the
      levels of which in some individuals were unexpectedly high in response to AdHu26.
      The magnitude of T-cell responses to AdHu5 correlated with those to AdHu26,
      suggesting T-cell recognition of conserved epitopes. In mice, all of the
      different Ad vectors induced CD8(+) T-cell responses that were comparable in
      their magnitudes and cytokine production profiles. Prime-boost regimens comparing
      different combinations of Ad vectors failed to indicate that the sequential use
      of Ad vectors from distinct families resulted in higher immune responses than the
      use of serologically distinct Ad vectors from the same family. Moreover, the
      transgene product-specific antibody responses induced by the AdHu26 and AdC
      vectors were markedly lower than those induced by the AdHu5 vector. AdHu26
      vectors and, to a lesser extent, AdC vectors induced more potent Ad-neutralizing
      antibody responses. These results suggest that the potential of AdHu26 as a
      vaccine vector may suffer from limitations similar to those found for vectors
      based on other prevalent human Ads.

PMID- 20686036
TI  - Efficacious early antiviral activity of HIV Gag- and Pol-specific HLA-B 2705
      restricted CD8+ T cells.
AB  - The association between HLA-B 2705 and the immune control of human
      immunodeficiency virus type 1 (HIV-1) has previously been linked to the targeting
      of the HLA-B 2705-restricted Gag epitope KRWIILGLNK (KK10) by CD8(+) T cells. In
      order to better define the mechanisms of the HLA-B 2705 immune control of HIV, we
      first characterized the CD8(+) T-cell responses of nine highly active
      antiretroviral therapy (HAART)-naive B 2705-positive subjects. Unexpectedly, we
      observed a strong response to an HLA-B 2705-restricted Pol epitope, KRKGGIGGY
      (KY9), in 8/9 subjects. The magnitude of the KY9 response was only marginally
      lower than that of the KK10-specific response (median, 695 versus 867 spot
      forming cells [SFC]/million peripheral blood mononuclear cells [PBMCs]; not
      significant [NS]), and viral escape mutants were observed in both KY9 and KK10,
      resulting from selection pressure driven by the respective CD8(+) T-cell
      response. By comparing inhibitions of viral replication by CD8(+) T cells
      specific for the Gag KK10, Pol KY9, and Vpr VL9 HLA-B 2705-restricted epitopes,
      we observed a consistent hierarchy of antiviral efficacy (Gag KK10 > Pol KY9 >
      Vpr VL9). This hierarchy was associated with early recognition of HIV-1-infected
      cells, within 6 h of infection, by KK10- and KY9-specific CD8(+) T cells but not
      until 18 h postinfection by VL9-specific CD8(+) T cells. There was no association
      between antiviral efficacy and proliferative capacity, cytotoxicity,
      polyfunctionality, or T-cell receptor (TCR) avidity. These data are consistent
      with previous studies indicating an important role for the B 2705-Gag KK10
      response in the control of HIV but also suggest a previously unrecognized role
      played by the subdominant Pol-specific KY9 response in HLA-B 2705-mediated
      control of HIV and that the recognition of HIV-infected cells by CD8(+) T cells
      early in the viral life cycle may be important for viral containment in HIV
      infected individuals.

PMID- 20686037
TI  - High level of genetic compatibility between swine-origin H1N1 and highly
      pathogenic avian H5N1 influenza viruses.
AB  - Reassortment is an important mechanism for the evolution of influenza viruses.
      Here, we coinfected cultured cells with the pandemic swine-origin influenza virus
      (S-OIV) and a contemporary H5N1 virus and found that these two viruses have high
      genetic compatibility. Studies of human lung cell lines indicated that some
      reassortants had better growth kinetics than their parental viruses. We conclude
      that reassortment between these two viruses can occur and could create pandemic
      H5N1 viruses.

PMID- 20686038
TI  - Genomic characterization of severe acute respiratory syndrome-related coronavirus
      in European bats and classification of coronaviruses based on partial RNA
      dependent RNA polymerase gene sequences.
AB  - Bats may host emerging viruses, including coronaviruses (CoV). We conducted an
      evaluation of CoV in rhinolophid and vespertilionid bat species common in Europe.
      Rhinolophids carried severe acute respiratory syndrome (SARS)-related CoV at high
      frequencies and concentrations (26% of animals are positive; up to 2.4*10(8)
      copies per gram of feces), as well as two Alphacoronavirus clades, one novel and
      one related to the HKU2 clade. All three clades present in Miniopterus bats in
      China (HKU7, HKU8, and 1A related) were also present in European Miniopterus
      bats. An additional novel Alphacoronavirus clade (bat CoV [BtCoV]/BNM98-30) was
      detected in Nyctalus leisleri. A CoV grouping criterion was developed by
      comparing amino acid identities across an 816-bp fragment of the RNA-dependent
      RNA polymerases (RdRp) of all accepted mammalian CoV species (RdRp-based grouping
      units [RGU]). Criteria for defining separate RGU in mammalian CoV were a >4.8%
      amino acid distance for alphacoronaviruses and a >6.3% distance for
      betacoronaviruses. All the above-mentioned novel clades represented independent
      RGU. Strict associations between CoV RGU and host bat genera were confirmed for
      six independent RGU represented simultaneously in China and Europe. A SARS
      related virus (BtCoV/BM48-31/Bulgaria/2008) from a Rhinolophus blasii (Rhi bla)
      bat was fully sequenced. It is predicted that proteins 3b and 6 were highly
      divergent from those proteins in all known SARS-related CoV. Open reading frame 8
      (ORF8) was surprisingly absent. Surface expression of spike and staining with
      sera of SARS survivors suggested low antigenic overlap with SARS CoV. However,
      the receptor binding domain of SARS CoV showed higher similarity with that of
      BtCoV/BM48-31/Bulgaria/2008 than with that of any Chinese bat-borne CoV. Critical
      spike domains 472 and 487 were identical and similar, respectively. This study
      underlines the importance of assessments of the zoonotic potential of widely
      distributed bat-borne CoV.

PMID- 20686039
TI  - Persistence of genital tract T cell responses in HIV-infected women on highly
      active antiretroviral therapy.
AB  - Initiation of highly active antiretroviral therapy (HAART) for HIV-infected
      individuals is associated with control of viremia, improved CD4 counts, and
      declining systemic HIV-specific immune responses. While HAART effectively reduces
      plasma viremia, it remains unclear how effectively antiretroviral drugs reach
      mucosal surfaces, such as those of the genital tract. The aim of this study was
      to determine the effect of HAART on genital tract CD4 T cell reconstitution, HIV
      shedding, and HIV-specific T cell responses. Cervical cytobrush and blood
      specimens were obtained from 35 HIV-infected, HAART-naive women and 27 women on
      HAART in order to investigate HIV Gag-specific T cell responses by intracellular
      gamma interferon (IFN-gamma) staining. Interleukin 1beta (IL-1beta), IL-6, and IL
      8 concentrations were measured by enzyme-linked immunosorbent assays (ELISA). We
      show that for HIV-infected women, HAART is associated with significantly improved
      CD4 T cell counts both in blood and at the cervix. While HAART effectively
      suppressed both blood and cervical viremia, HIV-specific CD8 T cell responses in
      blood were lost, while those at the cervix were preserved.

PMID- 20686040
TI  - Virulence determinants of avian H5N1 influenza A virus in mammalian and avian
      hosts: role of the C-terminal ESEV motif in the viral NS1 protein.
AB  - We assessed the prediction that access of the viral NS1 protein to cellular PDZ
      domain protein networks enhances the virulence of highly pathogenic avian
      influenza A viruses. The NS1 proteins of most avian influenza viruses bear the C
      terminal ligand sequence Glu-Ser-Glu-Val (ESEV) for PDZ domains present in
      multiple host proteins, whereas no such motif is found in the NS1 homologues of
      seasonal human virus strains. Previous analysis showed that a C-terminal ESEV
      motif increases viral virulence when introduced into the NS1 protein of mouse
      adapted H1N1 influenza virus. To examine the role of the PDZ domain ligand motif
      in avian influenza virus virulence, we generated three recombinants, derived from
      the prototypic H5N1 influenza A/Vietnam/1203/04 virus, expressing NS1 proteins
      that either have the C-terminal ESEV motif or the human influenza virus RSKV
      consensus or bear a natural truncation of this motif, respectively. Cell
      biological analyses showed strong control of NS1 nuclear migration in infected
      mammalian and avian cells, with only minor differences between the three
      variants. The ESEV sequence attenuated viral replication on cultured human,
      murine, and duck cells but not on chicken fibroblasts. However, all three viruses
      caused highly lethal infections in mice and chickens, with little difference in
      viral titers in organs, mean lethal dose, or intravenous pathogenicity index.
      These findings demonstrate that a PDZ domain ligand sequence in NS1 contributes
      little to the virulence of H5N1 viruses in these hosts, and they indicate that
      this motif modulates viral replication in a strain- and host-dependent manner.

PMID- 20686041
TI  - Rearranged JC virus noncoding control regions found in progressive multifocal
      leukoencephalopathy patient samples increase virus early gene expression and
      replication rate.
AB  - Polyomavirus JC (JCV) infects ~ 60% of the general population, followed by
      asymptomatic urinary shedding in ~ 20%. In patients with pronounced
      immunodeficiency, including HIV/AIDS, JCV can cause progressive multifocal
      leukoencephalopathy (PML), a devastating brain disease of high mortality. While
      JCV in the urine of healthy people has a linear noncoding control region called
      the archetype NCCR (at-NCCR), JCV in brain and cerebrospinal fluid (CSF) of PML
      patients bear rearranged NCCRs (rr-NCCRs). Although JCV NCCR rearrangements are
      deemed pathognomonic for PML, their role as a viral determinant is unclear. We
      sequenced JCV NCCRs found in CSF of eight HIV/AIDS patients newly diagnosed with
      PML and analyzed their effect on early and late gene expression using a
      bidirectional reporter vector recapitulating the circular polyomavirus early and
      late gene organization. The rr-NCCR sequences were highly diverse, but all
      increased viral early reporter gene expression in progenitor-derived astrocytes,
      glia-derived cells, and human kidney compared to the expression levels with the
      at-NCCR. The expression of simian virus 40 (SV40) large T antigen or HIV Tat
      expression in trans was associated with a strong increase of at-NCCR-controlled
      early gene expression, while rr-NCCRs were less responsive. The insertion of rr
      NCCRs into the JCV genome backbone revealed higher viral replication rates for rr
      NCCR compared to those of the at-NCCR JCV in human progenitor-derived astrocytes
      or glia cells, which was abrogated in SV40 large T-expressing COS-7 cells. We
      conclude that naturally occurring JCV rr-NCCR variants from PML patients confer
      increased early gene expression and higher replication rates compared to those of
      at-NCCR JCV and thereby increase cytopathology.

PMID- 20686042
TI  - Convergence of Kaposi's sarcoma-associated herpesvirus reactivation with Epstein
      Barr virus latency and cellular growth mediated by the notch signaling pathway in
      coinfected cells.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent of primary
      effusion lymphoma (PEL). All PEL cell lines are infected with KSHV, and 70% are
      coinfected with Epstein-Barr virus (EBV). KSHV reactivation from latency requires
      promoter-specific transactivation by the KSHV Rta protein through interactions
      with RBP-Jk (CSL), the cellular DNA-binding component of the Notch signal
      transduction pathway. EBV transformation of primary B cells requires EBV nuclear
      antigen 2 (EBNA-2) to interact with RBP-Jk to direct the latent viral and
      cellular gene expression program. Although KSHV Rta and EBV EBNA-2 both require
      RBP-Jk for transactivation, previous studies have suggested that RBP-Jk-dependent
      transactivators do not function identically. We have found that the EBV latent
      protein LMP-1 is expressed in less than 5% of KSHV(+)/EBV(+) PEL cells but is
      induced in an Rta-dependent fashion when KSHV reactivates. KSHV Rta
      transactivates the EBV latency promoters in an RBP-Jk-dependent fashion and forms
      a ternary complex with RBP-Jk on the promoters. In B cells that are conditionally
      transformed by EBV alone, we show that KSHV Rta complements a short-term EBNA-2
      growth deficiency in an autocrine/paracrine manner. Complementation of EBNA-2
      deficiency by Rta depends on RBP-Jk and LMP-1, and Rta transactivation is
      required for optimal growth of KSHV(+)/EBV(+) PEL lines. Our data suggest that
      Rta can contribute to EBV-driven cellular growth by transactivating RBP-Jk
      dependent EBV latency genes. However, our data also suggest that EBNA-2 and Rta
      induce distinct alterations in the cellular proteomes that contribute to the
      growth of infected cells.

PMID- 20686043
TI  - Infectious Lassa virus, but not filoviruses, is restricted by BST-2/tetherin.
AB  - Bone marrow stromal antigen 2 (BST-2/tetherin) is a cellular membrane protein
      that inhibits the release of HIV-1. We show for the first time, using infectious
      viruses, that BST-2 also inhibits egress of arenaviruses but has no effect on
      filovirus replication and spread. Specifically, infectious Lassa virus (LASV)
      release significantly decreased or increased in human cells in which BST-2 was
      either stably expressed or knocked down, respectively. In contrast, replication
      and spread of infectious Zaire ebolavirus (ZEBOV) and Lake Victoria marburgvirus
      (MARV) were not affected by these conditions. Replication of infectious Rift
      Valley fever virus (RVFV) and cowpox virus (CPXV) was also not affected by BST-2
      expression. Elevated cellular levels of human or murine BST-2 inhibited the
      release of virus-like particles (VLPs) consisting of the matrix proteins of
      multiple highly virulent NIAID Priority Pathogens, including arenaviruses (LASV
      and Machupo virus [MACV]), filoviruses (ZEBOV and MARV), and paramyxoviruses
      (Nipah virus). Although the glycoproteins of filoviruses counteracted the
      antiviral activity of BST-2 in the context of VLPs, they could not rescue
      arenaviral (LASV and MACV) VLP release upon BST-2 overexpression. Furthermore, we
      did not observe colocalization of filoviral glycoproteins with BST-2 during
      infection with authentic viruses. None of the arenavirus-encoded proteins rescued
      budding of VLPs in the presence of BST-2. Our results demonstrate that BST-2
      might be a broad antiviral factor with the ability to restrict release of a wide
      variety of human pathogens. However, at least filoviruses, RVFV, and CPXV are
      immune to its inhibitory effect.

PMID- 20686044
TI  - Variable loop glycan dependency of the broad and potent HIV-1-neutralizing
      antibodies PG9 and PG16.
AB  - The HIV-1-specific antibodies PG9 and PG16 show marked cross-isolate
      neutralization breadth and potency. Antibody neutralization has been shown to be
      dependent on the presence of N-linked glycosylation at position 160 in gp120. We
      show here that (i) the loss of several key glycosylation sites in the V1, V2, and
      V3 loops; (ii) the generation of pseudoviruses in the presence of various
      glycosidase inhibitors; and (iii) the growth of pseudoviruses in a mutant cell
      line (GnT1(-/-)) that alters envelope glycosylation patterns all have significant
      effects on the sensitivity of virus to neutralization by PG9 and PG16. However,
      the interaction of antibody is not inhibited by sugar monosaccharides
      corresponding to those found in glycans on the HIV surface. We show that some of
      the glycosylation effects described are isolate dependent and others are
      universal and can be used as diagnostic for the presence of PG9 and PG16-like
      antibodies in the sera of HIV-1-infected patients. The results suggest that PG9
      and PG16 recognize a conformational epitope that is dependent on glycosylation at
      specific variable loop N-linked sites. This information may be valuable for the
      design of immunogens to elicit PG9 and PG16-like antibodies, as well as
      constructs for cocrystallization studies.

PMID- 20686045
TI  - Epitope-specific regulatory CD4 T cells reduce virus-induced illness while
      preserving CD8 T-cell effector function at the site of infection.
AB  - The role of epitope-specific regulatory CD4 T cells in modulating CD8 T-cell
      mediated immunopathology during acute viral infection has not been well defined.
      In the murine model of respiratory syncytial virus (RSV) infection, CD8 T cells
      play an important role in both viral clearance and immunopathology. We have
      previously characterized two RSV epitope-specific CD4 T-cell responses with
      distinct phenotypic properties. One of them, the IA(b)M(209)-specific subset,
      constitutively expresses FoxP3 and modulates CD8 T-cell function in vitro. We
      show here that the IA(b)M(209)-specific CD4 T-cell response regulates CD8 T-cell
      function in vivo and is associated with diminished RSV-induced illness without
      affecting viral clearance at the site of infection. Achieving the optimal balance
      of regulatory and effector T-cell function is an important consideration for
      designing future vaccines.

PMID- 20686046
TI  - Identification of alpha interferon-induced genes associated with antiviral
      activity in Daudi cells and characterization of IFIT3 as a novel antiviral gene.
AB  - A novel assay was developed for Daudi cells in which the antiviral (AV) and
      antiproliferative (AP) activities of interferon (IFN) can be measured
      simultaneously. Using this novel assay, conditions allowing IFN AV protection but
      no growth inhibition were identified and selected. Daudi cells were treated under
      these conditions, and gene expression microarray analyses were performed. The
      results of the analysis identified 25 genes associated with IFN-alpha AV
      activity. Upregulation of 23 IFN-induced genes was confirmed by using reverse
      transcription-PCR. Of 25 gene products, 17 were detected by Western blotting at
      24 h. Of the 25 genes, 10 have not been previously linked to AV activity of IFN
      alpha. The most upregulated gene was IFIT3 (for IFN-induced protein with
      tetratricopeptide repeats 3). The results from antibody neutralizing experiments
      suggested an association of the identified genes with IFN-alpha AV activity. This
      association was strengthened by results from IFIT3-small interfering RNA
      transfection experiments showing decreased expression of IFIT3 and a reduction in
      the AV activity induced by IFN-alpha. Overexpression of IFIT3 resulted in a
      decrease of virus titer. Transcription of AV genes after the treatment of cells
      with higher concentrations of IFN having an AP effect on Daudi cells suggested
      pleiotropic functions of identified gene products.

PMID- 20686047
TI  - Chikungunya virus nonstructural protein 2 inhibits type I/II interferon
      stimulated JAK-STAT signaling.
AB  - Chikungunya virus (CHIKV) is an emerging human pathogen transmitted by
      mosquitoes. Like that of other alphaviruses, CHIKV replication causes general
      host shutoff, leading to severe cytopathicity in mammalian cells, and inhibits
      the ability of infected cells to respond to interferon (IFN). Recent research,
      however, suggests that alphaviruses may have additional mechanisms to circumvent
      the host's antiviral IFN response. Here we show that CHIKV replication is
      resistant to inhibition by interferon once RNA replication has been established
      and that CHIKV actively suppresses the antiviral IFN response by preventing IFN
      induced gene expression. Both CHIKV infection and CHIKV replicon RNA replication
      efficiently blocked STAT1 phosphorylation and/or nuclear translocation in
      mammalian cells induced by either type I or type II IFN. Expression of individual
      CHIKV nonstructural proteins (nsPs) showed that nsP2 was a potent inhibitor of
      IFN-induced JAK-STAT signaling. In addition, mutations in CHIKV-nsP2 (P718S) and
      Sindbis virus (SINV)-nsP2 (P726S) that render alphavirus replicons noncytopathic
      significantly reduced JAK-STAT inhibition. This host shutoff-independent
      inhibition of IFN signaling by CHIKV is likely to have an important role in viral
      pathogenesis.

PMID- 20686049
TI  - Differences between sexes in lower extremity alignment and muscle activation
      during soccer kick.
AB  - BACKGROUND: Injury risk in soccer varies by sex. Female soccer players face a
      greater risk of anterior cruciate ligament injury and patellofemoral problems,
      while male players are more likely to experience sports hernia symptoms. The
      purpose of this study was to test the hypothesis that females have different
      lower-extremity alignment and muscle activation patterns than males during the
      soccer kick. METHODS: Thirteen male and twelve female college soccer players
      underwent three-dimensional motion analysis and electromyography of seven muscles
      (iliacus, gluteus maximus, gluteus medius, vastus lateralis, vastus medialis,
      hamstrings, and gastrocnemius) in both the kicking and the supporting lower
      extremity and two additional muscles (hip adductors and tibialis anterior) in the
      kicking limb only. Five instep and five side-foot kicks were recorded for each
      player. Muscle activation was recorded as a percentage of maximum voluntary
      isometric contraction. RESULTS: The male soccer players had significantly higher
      mean muscle activation than their female counterparts with respect to the iliacus
      in the kicking limb (123% compared with 34% of maximal voluntary isometric
      contraction; p = 0.0007) and the gluteus medius (124% compared with 55%; p =
      0.005) and vastus medialis muscles (139% compared with 69%; p = 0.002) in the
      supporting limb. The supporting limb reached significantly greater mean hip
      adduction during the stance phase of the kick in the females compared with that
      in the males (15 degrees and 10 degrees, respectively; p = 0.006). CONCLUSIONS:
      Differences between the sexes in lower extremity alignment and muscle activation
      occur during the soccer instep and side-foot kicks. Decreased activation of the
      hip abductors and greater hip adduction in the supporting limb during the soccer
      kick in female athletes may be associated with their increased risk for anterior
      cruciate ligament injury.

PMID- 20686048
TI  - Small peptide inhibitors disrupt a high-affinity interaction between cytoplasmic
      dynein and a viral cargo protein.
AB  - Several viruses target the microtubular motor system in early stages of the viral
      life cycle. African swine fever virus (ASFV) protein p54 hijacks the microtubule
      dependent transport by interaction with a dynein light chain (DYNLL1/DLC8). This
      was shown to be a high-affinity interaction, and the residues gradually
      disappearing were mapped on DLC8 to define a putative p54 binding surface by
      nuclear magnetic resonance (NMR) spectroscopy. The potential of short peptides
      targeting the binding domain to disrupt this high-affinity protein-protein
      interaction was assayed, and a short peptide sequence was shown to bind and
      compete with viral protein binding to dynein. Given the complexity and number of
      proteins involved in cellular transport, the prevention of this viral-DLC8
      interaction might not be relevant for successful viral infection. Thus, we tested
      the capacity of these peptides to interfere with viral infection by disrupting
      dynein interaction with viral p54. Using this approach, we report on short
      peptides that inhibit viral growth.

PMID- 20686050
TI  - Commercial liquid bags as a potential source of venous air embolism in shoulder
      arthroscopy.
AB  - BACKGROUND: Venous air embolism is a rare but potentially fatal complication of
      arthroscopy. Fatal venous air embolism has been reported with as little as 100 mL
      of air entering the venous system. During liquid-only arthroscopy, avenues for
      air introduction into the joint are limited. Therefore, we hypothesized that
      commercially prepared 3-L saline-solution bags are a source of potentially fatal
      amounts of gas that can be introduced into the joint by arthroscopic pumps.
      METHODS: Eight 3-L arthroscopic saline-solution bags were obtained and visually
      inspected for air. The air was aspirated from four bags, and the volume of the
      air was recorded. A closed-system pump was prepared, and two 3-L bags were
      connected to it. The pump emptied into an inverted graduated cylinder immersed in
      a water bath. Both bags were allowed to run dry. Two more bags were then
      connected and also allowed to run dry. The air was quantified by the downward
      displacement of water. The experiment was then repeated with the four bags after
      the air had been aspirated from them. This experiment was performed at three
      institutions, with utilization of three pump systems and two brands of 3-L saline
      solution bags. RESULTS: Air was visualized in all bags, and the bags contained
      between 34 and 85 mL of air. Arthroscopic pumps can pump air efficiently through
      the tubing. The total volumes of gas ejected from the tubing after the four 3-L
      bags had been emptied were 75, 80, and 235 mL. When bags from which the air had
      been evacuated were used, no air exited the system. CONCLUSIONS: Because a saline
      solution arthroscopic pump is theoretically a closed system, venous air embolism
      has not been a concern. However, this study shows that it is possible to pump a
      fatal amount of air from 3-L saline-solution bags into an environment susceptible
      to the creation of emboli. Evacuation of air from the 3-L bags prior to use may
      eliminate this risk.

PMID- 20686051
TI  - Assessing the management of healthcare waste in Hawassa city, Ethiopia.
AB  - Inadequate management of healthcare waste is a serious concern in many developing
      countries due to the risks posed to human health and the environment. This study
      aimed to evaluate healthcare waste management in Hawassa city, Ethiopia. The
      study was conducted in nine healthcare facilities (HCFs) including hospitals
      (four), health centres (two) and higher clinics (three) in two phases, first to
      assess the waste management aspect and second to determine daily waste generation
      rate. The result showed that the median quantity of waste generated at the
      facilities was 3.46 kg bed(-1) day(-1) (range: 1.48-8.19 kg bed(-1) day(-1)). The
      quantity of waste per day generated at a HCF increased as occupancy increased (p
      < 0.001). The percentage hazardous waste generated at government HCFs was more
      than at private HCFs (p < 0.05). The proportion of hazardous waste (20-63.1%)
      generated at the different HCFs was much higher than the WHO recommendation (10
      25%). There was no waste segregation in most HCFs and only one used a complete
      color coding system. Solid waste and wastewater were stored, transported, treated
      and disposed inappropriately at all HCFs. Needle-stick injuries were prevalent in
      25-100% of waste handlers employed at these HCFs. Additionally, low levels of
      training and awareness of waste legislation was prevalent amongst staff. The
      study showed that management of healthcare waste at HCFs to be poor. Waste
      management practices need to be improved through improved legislation and
      enforcement, and training of staff in the healthcare facilities in Hawassa.

PMID- 20686052
TI  - Regulation of waste and waste management in Turkey.
AB  - Industrial and technological developments have increased rapidly throughout the
      world including Turkey. Furthermore, the population of Turkey is also increasing
      and the ever-increasing consumption creates larger amounts of waste materials and
      adversely affects the environment and human health. The development of a waste
      management and disposal system has become necessary in all countries of the
      world. As part of the process of seeking entry to the European Union, Turkey
      continues to prepare the necessary legislation to satisfy European Union
      regulations for the disposal of solid waste, packaging waste, biodegradable waste
      and medical waste materials within the framework of the strategy. An integrated
      waste management system is necessary for each town in Turkey that is suitable for
      the different contents and increasing amounts of waste produced. In the present
      study, Turkey's geographical regions were examined in terms of population and the
      total amount of solid waste generated in each province to produce detailed data
      for the Turkish Ministry of Environment and Forestry. As a result of this study,
      it is understood that Turkey has drawn up a 'road map' which will be followed by
      the 2008-2012 Waste Management Action Plan. To achieve this, the Ministry of the
      Environment and Forestry, Turkey and the municipalities must fulfill the tasks
      that have been allocated to them. Turkey will attain the European Union standards
      for waste management if these tasks lead to the achievement of the targets within
      the action plan.

PMID- 20686053
TI  - Commentary on articles by David H. Kim, MD, et al.: "institutional prescreening
      for detection and eradication of methicillin-resistant Staphylococcus aureus in
      patients undergoing elective orthopaedic surgery" and by Ran Schwarzkopf, MD, MS,
      et al.: "prevalence of Staphylococcus aureus colonization in orthopaedic surgeons
      and their patients. a prospective cohort controlled study".

PMID- 20686054
TI  - Commentary on an article by K.A. Egol, MD, et al.: "distal radial fractures in
      the elderly: operative compared with nonoperative treatment".

PMID- 20686055
TI  - The art of the knee examination: where has it gone?

PMID- 20686056
TI  - Computed tomography-based structural analysis for predicting fracture risk in
      children with benign skeletal neoplasms: comparison of specificity with that of
      plain radiographs.
AB  - BACKGROUND: The decision whether to treat benign skeletal lesions surgically can
      be difficult to make. The purpose of this study was to validate our previously
      published method of predicting fracture risk with use of quantitative computed
      tomography-based structural analysis. METHODS: We prospectively studied a group
      of children who presented to a major children's hospital with a benign
      appendicular skeletal lesion between 2002 and 2007. As in our previous study, the
      resistance of the affected bone to compressive, bending, and torsional loads was
      calculated with rigidity analysis performed with the use of serial transaxial
      quantitative computed tomography data obtained along the length of the bone
      containing the lesion and from homologous cross sections through the
      contralateral, normal bone. At each cross section, the ratio of the structural
      rigidity of the affected bone to that of the normal, contralateral bone was
      determined. RESULTS: Forty-one patients who had not received surgical treatment
      for the skeletal lesion met the criteria for our study. Thirty-four (83%) of
      these individuals completed our activity questionnaire at least two years after
      the quantitative computed tomography-based rigidity analysis. None of the
      patients for whom no increased fracture risk had been predicted by the rigidity
      analysis sustained a fracture, even though they had not received surgical
      treatment. CONCLUSIONS: Many considerations other than the predicted fracture
      risk are factored into the decision of whether to treat a benign skeletal lesion.
      However, this study indicated that quantitative computed tomography-based
      rigidity analysis is more specific (97% specificity) than criteria based on plain
      radiographs (12% specificity) for predicting the risk of a pathologic fracture
      since fracture risk indices based on lesion size alone fail to account for the
      compensatory remodeling of the host bone that occurs in response to the presence
      of the lesion in a growing child. LEVEL OF EVIDENCE: Prognostic Level I. See
      Instructions to Authors for a complete description of levels of evidence.

PMID- 20686057
TI  - A comparison of conventional guidewire alignment jigs with imageless computer
      navigation in hip resurfacing arthroplasty.
AB  - BACKGROUND: Correct positioning of the initial femoral guidewire is vital in
      order to prepare the femoral head properly for hip resurfacing. The purpose of
      the present investigation was to determine the accuracy and precision of the
      placement of the initial femoral guidewire with use of conventional alignment
      jigs and to compare the results with those of imageless computer navigation.
      METHODS: Five commercially available jigs (two lateral pin jigs, two neck
      centering jigs, and one head planing jig) were obtained. Four surgeons used each
      jig and navigation three times to insert a guidewire in 10 degrees of relative
      valgus and neutral version into individual synthetic femora. A single surgeon
      then used each jig three times to align the initial guidewire in 10 degrees of
      relative valgus and neutral version in each of ten human cadaver femora.
      Radiographs of the synthetic and human femora were made to assess and compare
      guidewire inclination and version between conventional instrumentation and
      navigation. RESULTS: Navigation provided ranges of error in the coronal guidewire
      alignment of up to eight times less than the conventional jigs, but both methods
      provided similar ranges of error for version. In both arms of the study, there
      were significant differences in coronal alignment accuracy between the two neck
      centering jigs. Next to navigation, one lateral pin jig provided the most
      accurate coronal placement of the initial guidewire whereas one neck centering
      jig provided the most precise coronal placement of the guidewire. Navigation was
      similar to conventional jigs in terms of the accuracy and precision of guidewire
      version. CONCLUSIONS: In hip resurfacing arthroplasty, the choice of a femoral
      alignment device may influence the accuracy and precision of guidewire insertion,
      ultimately impacting femoral component placement. Imageless computer navigation
      can facilitate accurate and precise coronal alignment of the initial femoral
      guidewire, superior to that of conventional instrumentation. CLINICAL RELEVANCE:
      The results of this study may aid surgeons in the selection of alignment
      instruments for placement of the initial femoral guidewire during hip
      resurfacing.

PMID- 20686058
TI  - The rising incidence of acromioplasty.
AB  - BACKGROUND: Acromioplasty is considered a technically simple procedure but has
      become controversial with regard to its indications and therapeutic value.
      METHODS: Two complementary databases were used to ascertain the frequency of
      acromioplasty over a recent span of time. In Part A, the New York Statewide
      Planning and Research Cooperative System (SPARCS) ambulatory surgery database was
      searched from 1996 to 2006 to identify all ambulatory surgery acromioplasties as
      well as all orthopaedic ambulatory surgery procedures. In Part B, the American
      Board of Orthopaedic Surgery (ABOS) database was searched from 1999 to 2008 to
      identify all arthroscopic acromioplasties as well as all orthopaedic procedures.
      RESULTS: Part A revealed that in 1996 there were 5571 acromioplasties in New York
      State, representing a population incidence of 30.0 per 100,000. In 2006 there
      were 19,743 acromioplasties, representing a population incidence of 101.9 per
      100,000. Over these eleven years, the volume of acromioplasties increased by
      254.4%, compared with only a 78.3% increase in the volume of all orthopaedic
      ambulatory surgery procedures. In 2006, as compared with 1996, patients were 2.4
      times more likely to have an acromioplasty compared with all other orthopaedic
      ambulatory procedures (p < 0.0001). Part B revealed that, in 1999, a mean of 2.6
      arthroscopic acromioplasties were reported per candidate for Board certification.
      In 2008 a mean of 6.3 arthroscopic acromioplasties per candidate were reported.
      Over these ten years, the mean number of arthroscopic acromioplasties reported
      increased by 142.3%, compared with only a 13.0% increase in the mean number of
      all orthopaedic surgery procedures. In 2008, as compared with 1999, candidates
      were 2.2 times more likely to report an arthroscopic acromioplasty compared with
      all other orthopaedic procedures (p < 0.0001). CONCLUSIONS: There has been a
      substantial increase in the overall volume and the population-based incidence of
      acromioplasties in recent years on both the state and national levels in the
      United States. The reasons for this increase have yet to be determined and are
      likely multifactorial, with patient-based, surgeon-based, and systems-based
      factors all playing a role.

PMID- 20686059
TI  - Distal radial fractures in the elderly: operative compared with nonoperative
      treatment.
AB  - BACKGROUND: There is much debate regarding the optimal treatment of displaced,
      unstable distal radial fractures in the elderly. The purpose of this
      retrospective review was to compare outcomes for elderly patients with a
      displaced distal radial fracture who were treated with or without surgical
      intervention. METHODS: This case-control study examined ninety patients over the
      age of sixty-five who were treated with or without surgery for a displaced distal
      radial fracture. All fractures were initially treated with closed reduction and
      splinting. Patients who failed an acceptable closed reduction were offered
      surgical intervention. Patients who did not undergo surgery were treated until
      healing with cast immobilization. Patients who underwent surgery were treated
      with either plate-and-screw fixation or external fixation. Baseline radiographs
      and functional scores were obtained prior to treatment. Follow-up was conducted
      at two, six, twelve, twenty-four, and fifty-two weeks. Clinical and radiographic
      follow-up was completed at each visit, while functional scores were obtained at
      the twelve, twenty-four, and fifty-two-week follow-up evaluations. Outcomes at
      fixed time points were compared between groups with standard statistical methods.
      RESULTS: Forty-six patients with a mean age of seventy-six years were treated
      nonoperatively, and forty-four patients with a mean age of seventy-three years
      were treated operatively. Other than age, there was no difference with respect to
      baseline demographics between the cohorts. At twenty-four weeks, patients who
      underwent surgery had better wrist extension (p = 0.04) than those who had not
      had surgery. At one year, this difference was not seen. No difference in
      functional status based on the Disabilities of the Arm, Shoulder and Hand scores
      and pain scores at any of the follow-up points was seen between the groups. Grip
      strength at one year was significantly better in the operative group.
      Radiographic outcome was superior for the patients in the operative group at each
      follow-up interval. There was no difference between the groups with regard to
      complications. CONCLUSIONS: Our findings suggest that minor limitations in the
      range of wrist motion and diminished grip strength, as seen with nonoperative
      care, do not seem to limit functional recovery at one year. LEVEL OF EVIDENCE:
      Therapeutic Level III. See Instructions to Authors for a complete description of
      levels of evidence.

PMID- 20686060
TI  - Reassessment of computerized wear measurement for total hip arthroplasty with
      correction for projectional image distortion: a brief follow-up report.
AB  - BACKGROUND: Wear of the ultra-high molecular weight polyethylene articular
      surface has been recognized as a major factor threatening the long-term success
      of total hip arthroplasty. Manual techniques that have been used to measure
      femoral head penetration into the polyethylene have been plagued with poor
      reproducibility and limited accuracy. Using a previously described phantom model
      simulating an unworn total hip arthroplasty, we previously demonstrated
      significant limitations in the accuracy of several widely used computerized wear
      measurement programs. A major component of these inaccuracies is projectional
      distortion of the femoral head and acetabular shell on the radiograph. These
      inaccuracies can be "corrected for" mathematically. METHODS: In the present
      follow-up study, we evaluated a widely used hip wear measurement software program
      (Hip Analysis Suite version 8.0.3.0) that corrects for these projectional errors
      with use of our previously described "zero wear" phantom model. A cementless
      metal-backed acetabular component was evaluated radiographically at three
      different cephalocaudad locations with respect to a radiopaque centering target.
      At all three positions, the cup was aligned in three different angles of planar
      abduction (35 degrees , 45 degrees , 55 degrees ) and four angles of planar
      anteversion (10 degrees , 20 degrees , 30 degrees , 40 degrees ). The accuracy
      and reproducibility of Hip Analysis Suite version 8.0.3.0 were determined and
      compared with the results obtained with the earlier version, Hip Analysis Suite
      version 4.0. RESULTS: Hip Analysis Suite version 8.0.3.0 was significantly more
      accurate than Hip Analysis Suite version 4.0 for determining linear wear and
      volumetric wear. Hip Analysis Suite version 8.0.3.0 was significantly more
      accurate for determining femoral head penetration at the different cephalocaudad
      acetabular positions and over the range of acetabular component anteversion and
      abduction angles in comparison with Hip Analysis Suite version 4.0. CONCLUSIONS:
      With use of the same methodology that was used to evaluate earlier versions of
      Hip Analysis Suite, the present study showed improvement in the accuracy of wear
      measurement with Hip Analysis Suite version 8.0.3.0 as compared with Hip Analysis
      Suite version 4.0. CLINICAL RELEVANCE: On the basis of the results of the present
      study, Hip Analysis Suite version 8.0.3.0 appears to fulfill the needs for a user
      friendly, efficient, and accurate method of assessment of polyethylene wear
      following total hip arthroplasty.

PMID- 20686061
TI  - Improving clinical recognition of Marfan syndrome.
AB  - BACKGROUND: Marfan syndrome is a potentially fatal disorder with cardiovascular,
      skeletal, and other manifestations that may also be seen in individuals without
      Marfan syndrome, making diagnosis difficult. Our goals were (1) to examine the
      ways in which patients have been recognized as having Marfan syndrome, (2) to
      examine the prevalence of current diagnostic findings, and (3) to determine which
      physically evident features are most sensitive and specific for referral to
      confirm a diagnosis of Marfan syndrome. METHODS: Between 2005 and 2007, we
      prospectively studied 183 consecutive patients with identified Marfan syndrome
      (Marfan group) and 1257 orthopaedic patients and family members (non-Marfan
      group). For the Marfan group, we recorded age at the time of recognition and the
      methods by which the syndrome was recognized; we used Ghent criteria to identify
      physically and radiographically evident features. For the non-Marfan group, we
      examined for Ghent criteria that could be noted on the basis of a routine
      history, physical examination, or radiographs. We used means, odds ratios, and
      frequencies to analyze the diagnostic use of each finding (alpha = 0.05).
      RESULTS: According to the Ghent criteria, 27% of patients in the Marfan group
      (mean age at the time of diagnosis, 7.3 years) had major skeletal involvement
      whereas 19% had zero or one skeletal feature. The most common physical features
      were craniofacial characteristics, high-arched palate, positive thumb and wrist
      signs, and scoliosis. In the non-Marfan group, 83% had one skeletal feature, 13%
      had two skeletal features, and 4% had three skeletal features or more. The
      physical features with the highest diagnostic yield were craniofacial
      characteristics, thumb and wrist signs, pectus excavatum, and severe hindfoot
      valgus. CONCLUSIONS: Musculoskeletal clinicians should be aware of the diagnostic
      features of Marfan syndrome. Patients with three to four physically evident
      features, or two highly specific features (e.g., thumb and wrist signs,
      craniofacial features, dural ectasia, or protrusio), should be carefully
      reexamined and possibly referred for an echocardiogram or a genetics
      consultation. LEVEL OF EVIDENCE: Diagnostic Level II. See Instructions to Authors
      for a complete description of levels of evidence.

PMID- 20686062
TI  - Musculoskeletal findings of Loeys-Dietz syndrome.
AB  - BACKGROUND: Loeys-Dietz syndrome is a recently recognized multisystemic disorder
      caused by mutations in the genes encoding the transforming growth factor-beta
      receptor. It is characterized by aggressive aneurysm formation and vascular
      tortuosity. We report the musculoskeletal demographic, clinical, and imaging
      findings of this syndrome to aid in its diagnosis and treatment. METHODS: We
      retrospectively analyzed the demographic, clinical, and imaging data of sixty
      five patients with Loeys-Dietz syndrome seen at one institution from May 2007
      through December 2008. RESULTS: The patients had a mean age of twenty-one years,
      and thirty-six of the sixty-five patients were less than eighteen years old.
      Previous diagnoses for these patients included Marfan syndrome (sixteen patients)
      and Ehlers-Danlos syndrome (two patients). Spinal and foot abnormalities were the
      most clinically important skeletal findings. Eleven patients had talipes
      equinovarus, and nineteen patients had cervical anomalies and instability. Thirty
      patients had scoliosis (mean Cobb angle [and standard deviation], 30 degrees +/-
      18 degrees ). Two patients had spondylolisthesis, and twenty-two of thirty-three
      who had computed tomography scans had dural ectasia. Thirty-five patients had
      pectus excavatum, and eight had pectus carinatum. Combined thumb and wrist signs
      were present in approximately one-fourth of the patients. Acetabular protrusion
      was present in approximately one-third of the patients and was usually mild.
      Fourteen patients had previous orthopaedic procedures, including scoliosis
      surgery, cervical stabilization, clubfoot correction, and hip arthroplasty.
      Features of Loeys-Dietz syndrome that are important clues to aid in making this
      diagnosis include bifid broad uvulas, hypertelorism, substantial joint laxity,
      and translucent skin. CONCLUSIONS: Patients with Loeys-Dietz syndrome commonly
      present to the orthopaedic surgeon with cervical malformations, spinal and foot
      deformities, and findings in the craniofacial and cutaneous systems. LEVEL OF
      EVIDENCE: Therapeutic Level IV. See Instructions to Authors for a complete
      description of levels of evidence.

PMID- 20686063
TI  - Prioritizing perioperative quality improvement in orthopaedic surgery.
AB  - BACKGROUND: Surgical quality improvement has received increasing attention in
      recent years, but it is not clear where orthopaedic surgeons should focus their
      efforts for the greatest impact on perioperative safety and quality. We sought to
      guide these efforts by prioritizing orthopaedic procedures according to those
      that generate the greatest number of adverse events. METHODS: We used data from
      the American College of Surgeons National Surgical Quality Improvement Program
      (ACS NSQIP) to identify all patients who had undergone an orthopaedic surgical
      procedure between 2005 and 2007 (n = 7970). Patients were assigned to forty-four
      unique procedure groups on the basis of the Current Procedural Terminology (CPT)
      codes. We first assessed the relative contribution of each procedure group to the
      overall number of adverse events in the first thirty postoperative days, and we
      followed that with a description of their relative contribution to an excess
      length of stay in the hospital. RESULTS: Ten procedures accounted for 70% of the
      adverse events and 65% of the excess hospital days. Hip fracture repair accounted
      for the greatest share of adverse events, followed by total knee arthroplasty,
      total hip arthroplasty, revision total hip arthroplasty, knee arthroscopy,
      laminectomy, lumbar/thoracic arthrodesis, and femoral fracture repair. No other
      procedure group accounted for >2% of the adverse events. CONCLUSIONS: Only a few
      procedures account for the vast majority of adverse events in the first thirty
      days following orthopaedic surgery. Concentrating quality-improvement efforts on
      these procedures may be an effective way for surgeons and other stakeholders to
      improve perioperative care and reduce costs in orthopaedic surgery. LEVEL OF
      EVIDENCE: Prognostic Level II. See Instructions to Authors for a complete
      description of levels of evidence.

PMID- 20686064
TI  - Cryptococcal abscess imitating a soft-tissue sarcoma in an immunocompetent host:
      a case report.

PMID- 20686065
TI  - Massive tears of the rotator cuff.
AB  - Repair of massive rotator cuff tears is technically difficult but often feasible.
      Technical and biological challenges to a successful repair include inelastic poor
      quality tendon tissue, scarring, muscle atrophy, and fatty infiltration. Fatty
      infiltration of the involved rotator cuff muscles has been identified as an
      important negative prognostic factor for the outcome after repair of massive
      rotator cuff tears. Tendon transfer is a good option for young patients and
      manual laborers with an irreparable massive rotator cuff tear. Arthroplasty can
      be considered for the treatment of symptomatic massive rotator cuff tears in
      patients who have glenohumeral arthritis.

PMID- 20686066
TI  - Protein kinase C-{delta} regulates the subcellular localization of Shc in H2O2
      treated cardiomyocytes.
AB  - Protein kinase C-delta (PKCdelta) exerts important cardiac actions as a lipid
      regulated kinase. There is limited evidence that PKCdelta also might exert an
      additional kinase-independent action as a regulator of the subcellular
      compartmentalization of binding partners such as Shc (Src homologous and
      collagen), a family of adapter proteins that play key roles in growth regulation
      and oxidative stress responses. This study shows that native PKCdelta forms
      complexes with endogenous Shc proteins in H(2)O(2)-treated cardiomyocytes;
      H(2)O(2) treatment also leads to the accumulation of PKCdelta and Shc in a
      detergent-insoluble cytoskeletal fraction and in mitochondria. H(2)O(2)-dependent
      recruitment of Shc isoforms to cytoskeletal and mitochondrial fractions is
      amplified by wild-type-PKCdelta overexpression, consistent with the notion that
      PKCdelta acts as a signal-regulated scaffold to anchor Shc in specific
      subcellular compartments. However, overexpression studies with kinase-dead (KD)
      PKCdelta-K376R (an ATP-binding mutant of PKCdelta that lacks catalytic activity)
      are less informative, since KD-PKCdelta-K376R aberrantly localizes as a
      constitutively tyrosine-phosphorylated enzyme to detergent-insoluble and
      mitochondrial fractions of resting cardiomyocytes; relatively little KD-PKCdelta
      K376R remains in the cytosolic fraction. The aberrant localization and tyrosine
      phosphorylation patterns for KD-PKCdelta-K376R do not phenocopy the properties of
      native PKCdelta, even in cells chronically treated with GF109203X to inhibit
      PKCdelta activity. Hence, while KD-PKCdelta-K376R overexpression increases Shc
      localization to the detergent-insoluble and mitochondrial fractions, the
      significance of these results is uncertain. Our studies suggest that experiments
      using KD-PKCdelta-K376R overexpression as a strategy to competitively inhibit the
      kinase-dependent actions of native PKCdelta or to expose the kinase-independent
      scaffolding functions of PKCdelta should be interpreted with caution.

PMID- 20686067
TI  - Characterization of hTERT-immortalized osteoblast cell lines generated from wild
      type and connexin43-null mouse calvaria.
AB  - The gap junction protein connexin43 (Cx43) has been proposed to play key roles in
      bone differentiation and mineralization, but underlying cellular mechanisms are
      not totally understood. To further explore roles of Cx43 in these processes, we
      immortalized calvarial osteoblasts from wild-type and Cx43-null mice using human
      telomerase reverse transcriptase (hTERT). Osteoblastic (MOB) cell lines were
      generated from three individual wild-type and three individual Cx43-null mouse
      calvaria. Average population doubling times of the cell lines were higher than of
      the primary osteoblasts but did not greatly differ with regard to genotype.
      Modest to high level of Cx45 expression was detected in MOBs of both genotypes.
      Most of the cell lines expressed osteoblastic markers [Type I collagen,
      osteopontin, osteocalcin, parathyroid hormone/parathyroid hormone-related peptide
      receptor (PTH/PTHrP), periostin (OSF-2), osterix (Osx), runt-related
      transcription factor 2 (Runx2), alkaline phosphatase (ALP)], and mineralization
      was comparable to that of primary osteoblasts. Two MOB cell lines from each
      genotype with most robust maintenance of osteoblast lineage markers were analyzed
      in greater detail, revealing that the Cx43-null cell lines showed a significant
      delay in early differentiation (up to 9 days in culture). Matrix mineralization
      was markedly delayed in one of the Cx43-null lines and slightly delayed in the
      other. These findings comparing new and very stable wild-type and Cx43-null
      osteoblastic cell lines define a role for Cx43 in early differentiation and
      mineralization stages of osteoblasts and further support the concept that Cx43
      plays important role in the cellular processes associated with skeleton function.

PMID- 20686068
TI  - Cystic fibrosis transmembrane conductance regulator is involved in airway
      epithelial wound repair.
AB  - The role of cystic fibrosis (CF) transmembrane conductance regulator (CFTR) in
      airway epithelial wound repair was investigated using normal human bronchial
      epithelial (NHBE) cells and a human airway epithelial cell line (Calu-3) of
      serous gland origin. Measurements of wound repair were performed using continuous
      impedance sensing to determine the time course for wound closure. Control
      experiments showed that the increase in impedance corresponding to cell migration
      into the wound was blocked by treatment with the actin polymerization inhibitor,
      cytochalasin D. Time lapse imaging revealed that NHBE and Calu-3 cell wound
      closure was dependent on cell migration, and that movement occurred as a
      collective sheet of cells. Selective inhibition of CFTR activity with CFTR(inh)
      172 or short hairpin RNA silencing of CFTR expression produced a significant
      delay in wound repair. The CF cell line UNCCF1T also exhibited significantly
      slower migration than comparable normal airway epithelial cells. Inhibition of
      CFTR-dependent anion transport by treatment with CFTR(inh)-172 slowed wound
      closure to the same extent as silencing CFTR protein expression, indicating that
      ion transport by CFTR plays a critical role in migration. Moreover, morphologic
      analysis of migrating cells revealed that CFTR inhibition or silencing
      significantly reduced lamellipodia protrusion. These findings support the
      conclusion that CFTR participates in airway epithelial wound repair by a
      mechanism involving anion transport that is coupled to the regulation of
      lamellipodia protrusion at the leading edge of the cell.

PMID- 20686069
TI  - Properties of the Arg376 residue of the proton-coupled folate transporter (PCFT
      SLC46A1) and a glutamine mutant causing hereditary folate malabsorption.
AB  - The proton-coupled folate transporter (PCFT-SLC46A1) is required for intestinal
      folate absorption and is mutated in the autosomal recessive disorder, hereditary
      folate malabsorption (HFM). This report characterizes properties and requirements
      of the R376 residue in PCFT function, including a R376Q mutant associated with
      HFM. Gln, Cys, and Ala substitutions resulted in markedly impaired transport of 5
      formyltetrahydrofolate (5-FTHF) and 5-methyltetrahydrofolate (5-MTHF) due to an
      increase in K(m) and decrease in V(max) in HeLa R1-11 transfectants lacking
      endogenous folate transport function. In contrast, although the influx K(m) for
      pemetrexed was increased, transport was fully preserved at saturating
      concentrations and enhanced for the like-charged R376K- and R376H-PCFT.
      Pemetrexed and 5-FTHF influx mediated by R376Q-PCFT was markedly decreased at pH
      5.5 compared with wild-type PCFT. However, while pemetrexed transport was
      substantially preserved at low pH (4.5-5.0), 5-FTHF transport remained very low.
      Electrophysiological studies in Xenopus oocytes demonstrated that 1) the R376Q
      mutant, like wild-type PCFT, transports protons in the absence of folate
      substrate, and in this respect has channel-like properties; and 2) the influx
      K(m) mediated by R376Q-PCFT is increased for 5-MTHF, 5-FTHF, and pemetrexed. The
      data suggest that mutation of the R376 residue to Gln impairs proton binding
      which, in turn, modulates the folate-binding pocket and depresses the rate of
      conformational alteration of the carrier, a change that appears to be, in part,
      substrate dependent.

PMID- 20686070
TI  - S100A1 promotes action potential-initiated calcium release flux and force
      production in skeletal muscle.
AB  - The role of S100A1 in skeletal muscle is just beginning to be elucidated. We have
      previously shown that skeletal muscle fibers from S100A1 knockout (KO) mice
      exhibit decreased action potential (AP)-evoked Ca(2+) transients, and that S100A1
      binds competitively with calmodulin to a canonical S100 binding sequence within
      the calmodulin-binding domain of the skeletal muscle ryanodine receptor. Using
      voltage clamped fibers, we found that Ca(2+) release was suppressed at all test
      membrane potentials in S100A1(-/-) fibers. Here we examine the role of S100A1
      during physiological AP-induced muscle activity, using an integrative approach
      spanning AP propagation to muscle force production. With the voltage-sensitive
      indicator di-8-aminonaphthylethenylpyridinium, we first demonstrate that the AP
      waveform is not altered in flexor digitorum brevis muscle fibers isolated from
      S100A1 KO mice. We then use a model for myoplasmic Ca(2+) binding and transport
      processes to calculate sarcoplasmic reticulum Ca(2+) release flux initiated by
      APs and demonstrate decreased release flux and greater inactivation of flux in KO
      fibers. Using in vivo stimulation of tibialis anterior muscles in anesthetized
      mice, we show that the maximal isometric force response to twitch and tetanic
      stimulation is decreased in S100A1(-/-) muscles. KO muscles also fatigue more
      rapidly upon repetitive stimulation than those of wild-type counterparts. We
      additionally show that fiber diameter, type, and expression of key excitation
      contraction coupling proteins are unchanged in S100A1 KO muscle. We conclude that
      the absence of S100A1 suppresses physiological AP-induced Ca(2+) release flux,
      resulting in impaired contractile activation and force production in skeletal
      muscle.

PMID- 20686071
TI  - Microfibrils and fibrillin-1 induce integrin-mediated signaling, proliferation
      and migration in human endothelial cells.
AB  - Microfibrils are macromolecular complexes associated with elastin to form elastic
      fibers that endow extensible tissues, such as arteries, lungs, and skin, with
      elasticity property. Fibrillin-1, the main component of microfibrils, is a 350
      kDa glycoprotein for which genetic haploinsufficiency in humans can lead to
      Marfan syndrome, a severe polyfeatured pathology including aortic aneurysms and
      dissections. Microfibrils and fibrillin-1 fragments mediate adhesion of several
      cell types, including endothelial cells, while fibrillin-1 additionally triggers
      lung and mesangial cell migration. However, fibrillin-1-induced intracellular
      signaling is unknown. We have studied the signaling events induced in human
      umbilical venous endothelial cells (HUVECs) by aortic microfibrils as well as
      recombinant fibrillin-1 Arg-Gly-Asp (RGD)-containing fragments PF9 and PF14.
      Aortic microfibrils and PF14, not PF9, substantially and dose dependently
      increased HUVEC cytoplasmic and nuclear calcium levels measured using the
      fluorescent dye Fluo-3. This effect of PF14 was confirmed in bovine aortic
      endothelial cells. PF14 action in HUVECs was mediated by alphavbeta3 and
      alpha5beta1 integrins, phospholipase-C, inosital 1,4,5-trisphosphate, and
      mobilization of intracellular calcium stores, whereas membrane calcium channels
      were not or only slightly implicated, as shown in patch-clamp experiments.
      Finally, PF14 enhanced endothelial cell proliferation and migration. Hence,
      fibrillin-1 sequences may physiologically activate endothelial cells. Genetic
      fibrillin-1 deficiency could alter normal endothelial signaling and, since
      endothelium dysfunction is an important contributor to Marfan syndrome,
      participate in the arterial anomalies associated with this developmental disease.

PMID- 20686072
TI  - Expression profile and protein translation of TMEM16A in murine smooth muscle.
AB  - Recently, overexpression of the genes TMEM16A and TMEM16B has been shown to
      produce currents qualitatively similar to native Ca(2+)-activated Cl(-) currents
      (I(ClCa)) in vascular smooth muscle. However, there is no information about this
      new gene family in vascular smooth muscle, where Cl(-) channels are a major
      depolarizing mechanism. Qualitatively similar Cl(-) currents were evoked by a
      pipette solution containing 500 nM Ca(2+) in smooth muscle cells isolated from
      BALB/c mouse portal vein, thoracic aorta, and carotid artery. Quantitative PCR
      using SYBR Green chemistry and primers specific for transmembrane protein (TMEM)
      16A or the closely related TMEM16B showed TMEM16A expression as follows: portal
      vein > thoracic aorta > carotid artery > brain. In addition, several
      alternatively spliced variant transcripts of TMEM16A were detected. In contrast,
      TMEM16B expression was very low in smooth muscle. Western blot analysis with
      different antibodies directed against TMEM16A revealed a number of products with
      a consistent band at ~120 kDa, except portal vein, where an 80-kDa band
      predominated. TMEM16A protein was identified in the smooth muscle layers of 4-MUm
      thick slices of portal vein, thoracic aorta, and carotid artery. In isolated
      myocytes, fluorescence specific to a TMEM16A antibody was detected diffusely
      throughout the cytoplasm, as well as near the membrane. The same antibody used in
      Western blot analysis of lysates from vascular tissues also recognized an ~147
      kDa mouse TMEM16A-green fluorescent protein (GFP) fusion protein expressed in HEK
      293 cells, which correlated to a similar band detected by a GFP antibody. Patch
      clamp experiments revealed that I(ClCa) generated by transfection of TMEM16A-GFP
      in HEK 293 cells displayed remarkable similarities to I(ClCa) recorded in
      vascular myocytes, including slow kinetics, steep outward rectification, and a
      response similar to the pharmacological agent niflumic acid. This study shows
      that TMEM16A expression is robust in murine vascular smooth muscle cells,
      consolidating the view that this gene is a viable candidate for the native Ca(2+)
      activated Cl(-) channel in this cell type.

PMID- 20686073
TI  - Protein tyrosine phosphatase PTPepsilonM negatively regulates PDGF beta-receptor
      signaling induced by high glucose and PDGF in vascular smooth muscle cells.
AB  - Vascular smooth muscle cell (VSMC) proliferation and migration and vascular
      endothelial cell (VEC) dysfunction are closely associated with the development of
      atherosclerosis. We previously demonstrated that protein tyrosine phosphatase
      epsilon M (PTPepsilonM) promotes VEC survival and migration. The present study
      investigates the biological functions of PTPepsilonM in VSMCs and determines
      whether PTPepsilonM is implicated in diabetes-accelerated atherosclerosis. We
      overexpressed wild-type and inactive PTPepsilonM and an small interfering RNA
      (siRNA) of PTPepsilonM by using an adenovirus vector to investigate the effects
      of PTPepsilonM upon platelet-derived growth factor (PDGF)- and high glucose (HG)
      induced responses of rat VSMCs in vitro. We found that PTPepsilonM decreased PDGF
      induced DNA synthesis and migration by reducing the phosphorylation level of the
      PDGF beta-receptor (PDGFRbeta) with subsequently suppressed H(2)O(2) generation.
      The HG content in the medium generated H(2)O(2), upregulated PDGFRbeta expression
      and its tyrosine-phosphorylation, and elevated NADPH oxidase 1 (Nox1) expression
      even without exogenous PDGF, all of which were downregulated by PTPepsilonM. The
      PDGFR inhibitor AG1296 also blocked HG-induced Nox1 expression and H(2)O(2)
      production. Moreover, HG suppressed PTPepsilonM expression itself, which was
      blocked by the antioxidant N-acetyl-l-cysteine. The effects of PTPepsilonM siRNA
      were the opposite of those of wild-type PTPepsilonM. Therefore, PTPepsilonM
      negatively regulates PDGFRbeta-mediated signaling pathways that are crucial for
      the pathogenesis of atherosclerosis, and PTPepsilonM may be involved in diabetes
      accelerated atherosclerosis.

PMID- 20686074
TI  - Blunted IgE-mediated activation of mast cells in mice lacking the serum- and
      glucocorticoid-inducible kinase SGK3.
AB  - Previous studies have shown that pharmacological inhibition of the
      phosphoinositol-3 (PI3) kinase disrupts the activation of mast cells. Through
      phosphoinositide-dependent kinase PDK1, PI3 kinase activates the serum- and
      glucocorticoid-inducible kinase 3 (SGK3). The present study explored the role of
      SGK3 in mast cell function. Mast cells were isolated and cultured from bone
      marrow (BMMCs) of gene-targeted mice lacking SGK3 (sgk3(-/-)) and their wild-type
      littermates (sgk3(+/+)). BMMC numbers in the ear conch were similar in both
      genotypes. Stimulation with IgE and cognate antigen triggered the release of
      intracellular Ca(2+) and entry of extracellular Ca(2+). Influx of extracellular
      Ca(2+) but not Ca(2+) release from intracellular stores was significantly blunted
      in sgk3(-/-) BMMCs compared with sgk3(+/+) BMMCs. Antigen stimulation further led
      to a rapid increase of a K(+)-selective conductance in sgk3(+/+) BMMCs, an effect
      again blunted in sgk3(-/-) BMMCs. In contrast, the Ca(2+) ionophore ionomycin
      activated K(+) currents to a similar extent in sgk3(-/-) and in sgk3(+/+) BMMCs.
      beta-Hexosaminidase release, triggered by antigen stimulation, was also
      significantly decreased in sgk3(-/-) BMMCs. IgE-dependent anaphylaxis measured as
      a sharp decrease in body temperature upon injection of DNP-HSA antigen was again
      significantly blunted in sgk3(-/-) compared with sgk3(+/+) mice. Serum histamine
      levels measured 30 min after induction of an anaphylactic reaction were
      significantly lower in sgk3(-/-) than in sgk3(+/+) mice. In conclusion, both in
      vitro and in vivo function of BMMCs are impaired in gene targeted mice lacking
      SGK3. Thus SGK3 is critical for proper mast cell function.

PMID- 20686075
TI  - A new method for direct detection of the sites of actin polymerization in intact
      cells and its application to differentiated vascular smooth muscle.
AB  - Here we report and validate a new method, suitable broadly, for use in
      differentiated cells and tissues, for the direct visualization of actin
      polymerization under physiological conditions. We have designed and tested
      different versions of fluorescently labeled actin, reversibly attached to the
      protein transduction tag TAT, and have introduced this novel reagent into intact
      differentiated vascular smooth muscle cells (dVSMCs). A thiol-reactive version of
      the TAT peptide was synthesized by adding the amino acids glycine and cysteine to
      its NH(2)-terminus and forming a thionitrobenzoate adduct: viz. TAT-Cys-S-STNB.
      This peptide reacts readily with G-actin, and the complex is rapidly taken up by
      freshly enzymatically isolated dVSMC, as indicated by the fluorescence of a FITC
      tag on the TAT peptide. By comparing different versions of the construct, we
      determined that the optimal construct for biological applications is a
      nonfluorescently labeled TAT peptide conjugated to rhodamine-labeled actin. When
      TAT-Cys-S-STNB-tagged rhodamine actin (TSSAR) was added to live, freshly
      enzymatically isolated cells, we observed punctae of incorporated actin at the
      cortex of the cell. The punctae are indistinguishable from those we have
      previously reported to occur in the same cell type when rhodamine G-actin is
      added to permeabilized cells. Thus this new method allows the delivery of labeled
      G-actin into intact cells without disrupting the native state and will allow its
      further use to study the effect of physiological intracellular Ca(2+)
      concentration transients and signal transduction on actin dynamics in intact
      cells.

PMID- 20686076
TI  - Kinase activity-independent anchoring function of protein kinase C-{delta}. Focus
      on "Protein kinase C-{delta} regulates the subcellular localization of Shc in
      H2O2-treated cardiomyocytes".

PMID- 20686077
TI  - Microevolution of Mycobacterium tuberculosis in a tuberculosis patient.
AB  - Five Mycobacterium tuberculosis isolates were obtained from three body sites from
      a Dutch patient. The isolates displayed a single genotype by 24-locus MIRU-VNTR
      typing (except for a single locus not amplified from one isolate) but were
      differentiated by small variations in IS6110 fingerprints, spoligotypes, 6
      hypervariable MIRU-VNTR loci, and/or DiversiLab profiles, revealing patterns of
      microevolution in a clonal infection.

PMID- 20686078
TI  - Is repeat PCR needed for diagnosis of Clostridium difficile infection?
AB  - Patients with diarrhea, defined as loose or watery stool, and two or more
      Clostridium difficile tcdB PCR tests within 14 days of each other were
      investigated. Repeat PCR for 293 patients with a prior negative result yielded
      negative results in 396 (97.5%) of 406 tests. Ten new positives were detected,
      including one false positive. Repeat PCR within 7 days appears rarely useful,
      except for patients with evidence of a new infection.

PMID- 20686079
TI  - PCR-based pooling of dried blood spots for detection of malaria parasites:
      optimization and application to a cohort of Ugandan children.
AB  - Sensitive, high-throughput methods to detect malaria parasites in low
      transmission settings are needed. PCR-based pooling strategies may offer a
      solution. We first used laboratory-prepared samples to compare 2 DNA extraction
      and 4 PCR detection methods across a range of pool sizes and parasite densities.
      Pooled Chelex extraction of DNA, followed by nested PCR of cytochrome b, was the
      optimal strategy, allowing reliable detection of a single low-parasitemic sample
      (100 parasites/MUl) in pool sizes up to 50. This PCR-based pooling strategy was
      then compared with microscopy using 891 dried blood spots from a cohort of 77
      Ugandan children followed for 2 years in an urban setting of low endemicity.
      Among 419 febrile episodes, 35 cases of malaria were detected using the PCR-based
      pooling strategy and 40 cases using microscopy. All five cases of malaria not
      detected by PCR were from samples stored for >2 years with parasitemia of
      <6,000/MUl, highlighting the issue of possible DNA degradation with long-term
      storage of samples. Among 472 samples collected from asymptomatic children as
      part of routine surveillance, 15 (3.2%) were positive by PCR-based pooling
      compared to 4 (0.8%) by microscopy (P = 0.01). Thus, this PCR-based pooling
      strategy for detection of malaria parasites using dried blood spots offers a
      sensitive and efficient approach for malaria surveillance in low-transmission
      settings, enabling improved detection of asymptomatic submicroscopic infections
      and dramatic savings in labor and costs.

PMID- 20686080
TI  - Relatedness of human and animal Clostridium difficile PCR ribotype 078 isolates
      determined on the basis of multilocus variable-number tandem-repeat analysis and
      tetracycline resistance.
AB  - Totals of 102 and 56 Clostridium difficile type 078 strains of human and porcine
      origins, respectively, from four European countries were investigated by an
      optimized multilocus variable-number tandem-repeat analysis (MLVA) and for
      tetracycline susceptibility. Eighty-five percent of all isolates were genetically
      related, irrespective of human or porcine origin. Human strains were
      significantly more resistant to tetracycline than porcine strains. All
      tetracycline-resistant strains contained the Tn916-like transposon harboring the
      tet(M) gene. We conclude that strains from human and porcine origins are
      genetically related, irrespective of the country of origin. This may reflect a
      lack of diversity and/or common source.

PMID- 20686081
TI  - Incidence, risk factors, and outcomes of Panton-Valentine leukocidin-positive
      methicillin-susceptible Staphylococcus aureus infections in Auckland, New
      Zealand.
AB  - Panton-Valentine leukocidin (PVL) has been linked to invasive community-acquired
      methicillin-resistant Staphylococcus aureus infections. However, the association
      between disease and PVL-positive methicillin-susceptible Staphylococcus aureus
      (MSSA) has not been widely reported. We aimed to examine the epidemiology of PVL
      in clinical MSSA isolates from patients presenting to Auckland City Hospital.
      Four hundred eleven MSSA clinical isolates and 93 nasal carriage isolates were
      collected and tested for the presence of the lukSF-PV genes using PCR. The
      results were examined in light of host and disease factors. Multilocus sequence
      typing (MLST) was performed on a random subset of isolates to ensure that there
      was no single PVL-positive MSSA clone responsible for disease in Auckland. The
      prevalence of the lukSF-PV genes in MSSA isolates associated with disease
      (124/335; 37%) was not significantly different from the prevalence of the lukSF
      PV genes in MSSA nasal carriage isolates (29/93; 31% [P = 0.33]). PVL-positive
      MSSA isolates in Auckland are genetically diverse and come from a number of
      different clonal complexes. PVL-positive infections peaked at between 10 and 20
      years of age, with a subsequent decline. Pacific ethnicity, age, diagnosis of
      skin and soft tissue infection (SSTI), community-onset infection, and the need
      for surgical intervention were found by multivariate analysis to be independently
      associated with PVL-positive MSSA infection. More than one-third of MSSA
      infections in our patient population are caused by PVL-positive strains. Those
      patients with PVL-positive MSSA infection were more likely to be of Pacific
      ethnicity, be younger in age, have community-onset infection, have SSTI, and need
      surgical intervention.

PMID- 20686082
TI  - Biochip system for rapid and accurate identification of mycobacterial species
      from isolates and sputum.
AB  - The accurate detection of mycobacterial species from isolates and clinical
      samples is important for pathogenic diagnosis and treatment and for disease
      control. There is an urgent need for the development of a rapid, simple, and
      accurate detection method. We established a biochip assay system, including a
      biochip, sample preparation apparatus, hybridization instrument, chip washing
      machine, and laser confocal scanner equipped with interpretation software for
      automatic diagnosis. The biochip simultaneously identified 17 common
      mycobacterial species by targeting the differences in the 16S rRNA. The system
      was assessed with 64 reference strains and 296 Mycobacterium tuberculosis and 243
      nontuberculous mycobacterial isolates, as well as 138 other bacteria and 195
      sputum samples, and then compared to DNA sequencing. The entire biochip assay
      took 6 h. The concordance rate between the biochip assay and the DNA sequencing
      results was 100%. In conclusion, the biochip system provides a simple, rapid,
      reliable, and highly accurate clinical assay for determination of mycobacterial
      species in a 6-h procedure, from either culture isolates or sputum samples,
      allowing earlier pathogen-adapted antimicrobial therapy in patients.

PMID- 20686083
TI  - Internet-accessible DNA sequence database for identifying fusaria from human and
      animal infections.
AB  - Because less than one-third of clinically relevant fusaria can be accurately
      identified to species level using phenotypic data (i.e., morphological species
      recognition), we constructed a three-locus DNA sequence database to facilitate
      molecular identification of the 69 Fusarium species associated with human or
      animal mycoses encountered in clinical microbiology laboratories. The database
      comprises partial sequences from three nuclear genes: translation elongation
      factor 1alpha (EF-1alpha), the largest subunit of RNA polymerase (RPB1), and the
      second largest subunit of RNA polymerase (RPB2). These three gene fragments can
      be amplified by PCR and sequenced using primers that are conserved across the
      phylogenetic breadth of Fusarium. Phylogenetic analyses of the combined data set
      reveal that, with the exception of two monotypic lineages, all clinically
      relevant fusaria are nested in one of eight variously sized and strongly
      supported species complexes. The monophyletic lineages have been named informally
      to facilitate communication of an isolate's clade membership and genetic
      diversity. To identify isolates to the species included within the database,
      partial DNA sequence data from one or more of the three genes can be used as a
      BLAST query against the database which is Web accessible at FUSARIUM-ID
      (http://isolate.fusariumdb.org) and the Centraalbureau voor Schimmelcultures (CBS
      KNAW) Fungal Biodiversity Center (http://www.cbs.knaw.nl/fusarium).
      Alternatively, isolates can be identified via phylogenetic analysis by adding
      sequences of unknowns to the DNA sequence alignment, which can be downloaded from
      the two aforementioned websites. The utility of this database should increase
      significantly as members of the clinical microbiology community deposit in
      internationally accessible culture collections (e.g., CBS-KNAW or the Fusarium
      Research Center) cultures of novel mycosis-associated fusaria, along with
      associated, corrected sequence chromatograms and data, so that the sequence
      results can be verified and isolates are made available for future study.

PMID- 20686084
TI  - Evaluation of the Capilia TB assay for culture confirmation of Mycobacterium
      tuberculosis infections in Zambia and South Africa.
AB  - The performance and cost of the Capilia TB assay were evaluated for use in a
      resource-limited setting. The sensitivity and specificity were 99.6% and 99.5%,
      respectively. The incremental costs of the Capilia test were estimated to be
      $1.46 and $1.84 when the test was added to liquid and solid culture processes,
      respectively. These findings suggest that the Capilia TB assay represents a
      rapid, simple, and inexpensive Mycobacterium tuberculosis identification test
      that can be used in resource-limited settings.

PMID- 20686085
TI  - In vitro evaluation of antibiotic synergy for polymyxin B-resistant carbapenemase
      producing Klebsiella pneumoniae.
AB  - Since carbapenemase-producing Klebsiella pneumoniae strains were first reported
      in North Carolina, these highly resistant organisms have been isolated with
      increasing frequency, especially in the New York City area. Polymyxin B is one of
      the few antimicrobials that retain reliable activity against these organisms.
      However, polymyxin B MICs are elevated against K. pneumoniae isolates with
      increasing frequency, leaving clinicians with few therapeutic options. We
      investigated several antimicrobial agents for potential synergy with polymyxin B
      against 12 clinical strains of carbapenemase-producing K. pneumoniae. A broth
      microdilution assay using a 96-well plate was developed in which graded dilutions
      of polymyxin B and the study drug were incubated with resistant isolates in a
      checkerboard pattern. Polymyxin B was studied in combination with cefazolin,
      ceftriaxone, cefepime, imipenem, gentamicin, tigecycline, doxycycline, and
      rifampin. All K. pneumoniae strains tested positive for K. pneumoniae
      carbapenemase (KPC) genes by real-time PCR and had elevated polymyxin B MIC
      values ranging from 16 to 128 MUg/ml. Synergy was observed with the combination
      of polymyxin B and rifampin as well as with polymyxin B and doxycycline,
      resulting in at least a 4-fold decrease in the polymyxin B MIC. For both
      combinations, this effect occurred at physiologically achievable concentrations.
      Less pronounced synergy was noted with tigecycline and polymyxin B. No synergy
      was observed at physiologic concentrations with the other antimicrobials studied.
      These results suggest that rifampin, doxycycline, and tigecycline may be useful
      additions to polymyxin B in the treatment of infections caused by highly
      resistant carbapenemase-producing K. pneumoniae. Further studies are warranted to
      determine if these in vitro findings translate into clinical efficacy.

PMID- 20686086
TI  - Molecular Basis of pathogenicity in Helicobacter pylori clinical isolates.
AB  - This study identified pathogenicity genes in 40 Helicobacter pylori clinical
      isolates. The cagA, vacA, and iceA genes were detected in 65%, 97.5%, and 97.5%
      of the isolates, respectively. The cagA, iceA1, and vacAs1a/m1 genes were related
      to erosive gastritis, whereas the vacAs2/m2 and iceA2 genes were associated with
      enanthematous gastritis.

PMID- 20686087
TI  - Monascus ruber: invasive gastric infection caused by dried and salted fish
      consumption.
AB  - We report a case of invasive gastric infection caused by Monascus ruber observed
      in a patient from French Guiana with gastric adenocarcinoma. The originality of
      this case is that, first, this invasive mycosis is extremely rare and, second,
      the probable mode of infection was by the consumption of Monascus ruber
      contaminated food.

PMID- 20686088
TI  - Use of groESL as a target for identification of Abiotrophia, Granulicatella, and
      Gemella species.
AB  - We determined the groESL sequences of three species of nutritionally variant
      streptococci (Abiotrophia defectiva, Granulicatella adiacens, and Granulicatella
      elegans) and three Gemella species (Gemella morbillorum, Gemella haemolysans, and
      Gemella sanguinis). The nucleotide sequence similarities between the groES and
      groEL genes of the above genera were 41.7 to 85.9% and 63.7 to 84.3%,
      respectively. The intraspecies similarities of groESL sequences for the isolates
      of Abiotrophia and Granulicatella species were 94.4 to 97.8% for groES and 94.0
      to 98.2% for groEL. For Ge. morbillorum and Ge. sanguinis, all strains showed the
      same groESL spacer length (8 bp), and sequence identities within species were
      >97.8% for groES and >96.1% for groEL. However, higher intraspecies heterogeneity
      was observed in Ge. haemolysans. Phylogenetic analysis of groEL sequences
      separated the 6 isolates of Ge. haemolysans into two subgroups. Among these
      isolates, three isolates with the same groESL spacer region length (45 bp)
      clustered together but were distant from the ATCC reference strain (with a spacer
      length of 8 bp). The remaining three isolates, with a spacer length of 50 or 8
      bp, clustered together. Although 16S rRNA gene sequence analysis did not provide
      enough discrimination for the 6 Ge. haemolysans isolates, rpoB gene sequence
      analysis supported the subgrouping. Based on the obtained groESL sequences, we
      developed a multiplex PCR that enables simple, rapid, and accurate identification
      of Abiotrophia, Granulicatella, and Gemella at the genus level. This assay would
      be helpful for identifying these fastidious and slow-growing organisms in
      clinical laboratories.

PMID- 20686089
TI  - Trends in methicillin-resistant Staphylococcus aureus anovaginal colonization in
      pregnant women in 2005 versus 2009.
AB  - In 2005, the prevalence of methicillin-resistant Staphylococcus aureus (MRSA)
      anovaginal colonization in pregnant women at our center (Columbia University
      Medical Center) was 0.5%, and MRSA-colonized women were less likely to carry
      group B streptococcus (GBS). In this study, our objectives were to identify
      changing trends in the prevalence of MRSA and methicillin-susceptible S. aureus
      (MSSA) anovaginal colonization in pregnant women, to assess the association
      between MRSA and GBS colonization, and to characterize the MRSA strains. From
      February to July 2009, Lim broths from GBS surveillance samples were cultured for
      S. aureus. MRSA strains were identified by resistance to cefoxitin and
      characterized by MicroScan, staphylococcal cassette chromosome mec (SCCmec)
      typing, pulsed-field gel electrophoresis (PFGE), spa typing, and Panton-Valentine
      leukocidin PCR. A total of 2,921 specimens from different patients were analyzed.
      The prevalences of MSSA, MRSA, and GBS colonization were 11.8%, 0.6% and 23.3%,
      respectively. GBS colonization was associated with S. aureus colonization (odds
      ratio [OR], 1.9; 95% confidence interval [95% CI], 1.5 to 2.4). The frequencies
      of GBS colonization were similar in MRSA-positive (34.2%) versus MRSA-negative
      patients (21.8%) (P = 0.4). All MRSA isolates from 2009 and 13/14 isolates from
      2005 were SCCmec type IV or V, consistent with community-associated MRSA; 12/18
      (2009) and 0/14 (2005) isolates were the USA300 clone. Levofloxacin resistance
      increased from 14.3% (2005) to 55.6% (2009) (P = 0.028). In conclusion, the
      prevalence of MRSA anovaginal colonization in pregnant women in New York City,
      NY, remained stable from 2005 to 2009, and USA300 emerged as the predominant
      clone with a significant increase in levofloxacin-resistant isolates.

PMID- 20686090
TI  - Low frequency of CXCR4-using viruses in patients at the time of primary non
      subtype-B HIV-1 infection.
AB  - We used genotypic and phenotypic assays to estimate the frequency of X4/DM
      viruses in 131 patients infected with non-subtype-B viruses at the time of
      primary HIV-1 infection (PHI). All patients were enrolled in the French PRIMO
      Cohort from 1996 to 2007. Most strains belonged to CRF02_AG (51.1%) and subtype A
      (14.5%). Sixteen viruses (12.2%) were classified as CXCR4 tropic ("X4 strains")
      by the combined criteria of amino acids 11 and 25 of the V3 loop (11/25) and net
      charge rules and/or the SVMgeno2pheno(10%) algorithm: 6 strains by the combined
      genotypic rule, 7 by the SVMgeno2pheno(10%) algorithm, and 3, clustering in
      subtype D, by both algorithms. However, only one strain (0.8%), belonging to
      subtype A, was defined as a dual-tropic (DM) virus by the phenotypic assay. The
      67 CRF02_AG strains included 2 classified as X4 strains by the combined genotypic
      rule (3%) and 2 others classified as X4 strains by SVMgeno2pheno(10%) (3%), but
      none of these 4 strains was an X4 or DM strain according to the phenotypic assay.
      These results suggest that the cellular virus reservoir was established with X4
      strains in very few non-subtype-B-infected patients at the time of PHI. Genotypic
      predictions can overestimate the proportion of non-subtype-B X4 viruses at PHI.

PMID- 20686091
TI  - Congenital Trypanosoma cruzi infection in neonates and infants from two regions
      of Chile where Chagas' disease is endemic.

PMID- 20686092
TI  - Haemophilus influenzae outer membrane protein P6 molecular characterization may
      not differentiate all strains of H. Influenzae from H. haemolyticus.
AB  - Distinguishing nontypeable Haemophilus influenzae and Haemophilus haemolyticus
      isolates by outer membrane protein (OMP) P6 gene sequencing is complicated by
      sequence variants in isolates. Further testing using RapID NH and multilocus
      sequence analysis may not help identify some isolates. Translated OMP P6 gene
      sequences are not conserved among all isolates presumed to be H. influenzae.

PMID- 20686093
TI  - Identification, molecular characterization, and occurrence of two bovine
      hemoplasma species in Swiss cattle and development of real-time TaqMan
      quantitative PCR assays for diagnosis of bovine hemoplasma infections.
AB  - Concomitantly with an outbreak of fatal anaplasmosis in a cattle herd in
      Switzerland in 2002, we detected two bovine hemoplasma species in diseased
      animals: Mycoplasma wenyonii (formerly Eperythrozoon wenyonii) and a second,
      novel bovine hemoplasma species later designated "Candidatus Mycoplasma haemobos"
      (synonym, "Candidatus Mycoplasma haemobovis"). The second species was
      characterized by a shorter 16S rRNA gene. The aims of the present study were to
      provide a detailed molecular characterization of this species, to develop
      specific quantitative real-time PCR assays for the two bovine hemoplasma species,
      and to apply these assays in order to evaluate the prevalence and clinical
      significance of the hemoplasmas. Sequencing of the near-complete 16S rRNA gene of
      the second hemoplasma revealed that it was 94% identical to that of Mycoplasma
      haemofelis, an anemia-inducing feline hemoplasma species, but less than 85%
      identical to that of the bovine hemoplasma M. wenyonii. Using the newly developed
      assays, a total of 159 animals from the anaplasmosis outbreak were reexamined. In
      addition, we tested 57 clinically ill and 61 healthy Swiss cattle, as well as 47
      calves. Both hemoplasmas were highly prevalent in adult cattle but occurred
      rarely in calves. Animals from the herd with the fatal anemia outbreak were more
      frequently infected with M. wenyonii and exhibited higher M. wenyonii blood loads
      than animals with unrelated diseases and healthy animals. Coinfections may
      increase the pathogenicity and clinical significance of bovine hemoplasmosis.

PMID- 20686094
TI  - Evidence for amino acid changes in a 57-base-pair region of the highly conserved
      matrix gene of pandemic (H1N1) 2009 influenza A virus.

PMID- 20686095
TI  - Unexpected diversity of staphylococcal cassette chromosome mec type IV in
      methicillin-resistant Staphylococcus aureus strains.
AB  - Staphylococcal cassette chromosome mec (SCCmec) is a large mobile genetic element
      which is used frequently for subtyping of methicillin-resistant Staphylococcus
      aureus (MRSA) strains. MRSA SCCmec type IV not only predominates among community
      acquired MRSA (CA-MRSA) strains but also is associated with several genetic
      lineages of hospital-acquired MRSA (HA-MRSA) and with other species. The
      objective of this study was to investigate the diversity of MRSA strains
      classified as SCCmec type IV by using a multiplex PCR-based reverse line blot
      (mPCR/RLB) hybridization assay as well as spa typing and pulsed-field gel
      electrophoresis (PFGE). Sixty-two primer pairs and 63 probes were designed to
      interrogate each open reading frame (ORF) of SCCmec type IV sequences. A set of
      131 MRSA SCCmec type IV isolates were classified into 79 subtypes by this method.
      There was considerable concordance between SCCmec type IV subtyping, spa typing,
      and PFGE patterns for clinical isolates, and the stability of SCCmec type IV
      subtyping was comparable to that of the other two methods. Using an in-house
      computer program, we showed that a subset of 20 genetic markers could achieve the
      same level of discrimination between isolates as the full set of 62, with a
      Simpson's index of diversity of 0.975. SCCmec type IV has a much higher level of
      diversity than previously suggested. The application of the mPCR/RLB
      hybridization assay to MRSA SCCmec type IV subtyping can improve the
      discriminatory power and throughput of MRSA typing and has the potential to
      enhance rapid infection control surveillance and outbreak detection.

PMID- 20686096
TI  - Unusual "flesh-eating" strain of Escherichia coli.
AB  - We report an exceptional case of life-threatening Escherichia coli-induced
      necrotizing fasciitis. A combined host-pathogen genetic analysis explained the
      phenotype: the host displayed a susceptibility to intravascular coagulation, and
      the strain was capable of producing a necrotic toxin (cytotoxic necrotizing
      factor 1), showing how E. coli can be a dermonecrotic pathogen.

PMID- 20686097
TI  - Self-Regulation of Emotion, Functional Impairment, and Comorbidity Among
      ChildrenWith AD/HD.
AB  - OBJECTIVE: This study investigated the role of self-regulation of emotion in
      relation to functional impairment and comorbidity among children with and without
      AD/HD. METHOD: A total of 358 probands and their siblings participated in the
      study, with 74% of the sample participants affected by AD/HD. Parent-rated levels
      of emotional lability served as a marker for self-regulation of emotion. RESULTS:
      Nearly half of the children affected by AD/HD displayed significantly elevated
      levels of emotional lability versus 15% of those without this disorder. Children
      with AD/HD also displayed significantly higher rates of functional impairment,
      comorbidity, and treatment service utilization. Emotional lability partially
      mediated the association between AD/HD status and these outcomes. CONCLUSION:
      Findings lent support to the notion that deficits in the self-regulation of
      emotion are evident in a substantial number of children with AD/HD and that these
      deficits play an important role in determining functional impairment and
      comorbidity outcomes.

PMID- 20686098
TI  - Response-time variability is related to parent ratings of inattention,
      hyperactivity, and executive function.
AB  - OBJECTIVE: Individuals with ADHD are often characterized as inconsistent across
      many contexts. ADHD is also associated with deficits in executive function. We
      examined the relationships between response time (RT) variability on five brief
      computer tasks to parents' ratings of ADHD-related features and executive
      function in a group of children with a broad range of ADHD symptoms from none to
      full diagnosis. METHODS: We tested 98 children (mean age 9.9 +/- 1.4 years; 66
      boys) from community clinics on short tasks of executive control (TEC) and the
      Eriksen Flanker task, while a parent completed the Conners' Parent Rating Scale
      and Behavior Rating Inventory of Executive Function. RESULTS: Variability for two
      of the TEC tasks explained significant proportions of the variance of all five
      ADHD-related Conners' subscales and several executive function subscales. By
      contrast, variability on the flanker task or mean RTs for any task were not
      associated with any rating scale. CONCLUSION: The significant dimensional
      relationships observed between variability measures and parent ratings supported
      the utility of RT variability as an objective measure in ADHD and aspects of
      executive functioning that is superior to RT means or accuracy measures.

PMID- 20686099
TI  - Coexisting psychiatric problems and stressful life events in adults with symptoms
      of ADHD--a large Swedish population-based study of twins.
AB  - OBJECTIVE: To explore the associations of subtypes of adult ADHD with other
      psychiatric problems, stressful life events, and sex differences. METHOD: Odds
      ratios were calculated using information from 17,899 participants from a
      population-based survey of adult twins born in Sweden between 1959 and 1985.
      RESULTS: Symptoms of attention deficit hyperactivity disorder (ADHD) were
      associated with an increased risk for symptoms of (odds ratio [95% confidence
      interval]): generalized anxiety disorder (5.6 [4.3; 6.5]), major depression (2.8
      [2.4; 3.2]), bipolar disorder (8.0 [5.1; 12.6]), obsessive-compulsive disorder
      (3.9 [3.1; 4.9]), and alcohol dependence (2.6 [2.2; 3.1]). Symptoms of ADHD were
      found to be associated with an increased risk for stressful life events (1.8
      [1.3; 2.4]). No significant difference in comorbidity was observed between the
      two sexes. CONCLUSION: Both women and men with ADHD are at increased risk for
      symptoms of other psychiatric disorders. They are also at increased risk for
      stressful life events.

PMID- 20686100
TI  - Efficacy of atomoxetine in children with severe autistic disorders and symptoms
      of ADHD: an open-label study.
AB  - OBJECTIVE: This study aims to examine the efficacy of atomoxetine in treating
      symptoms of attention deficit hyperactivity disorder (ADHD) in children with
      severe autistic disorder. METHOD: Children with severe autistic disorder who had
      symptoms of ADHD were given atomoxetine for 10 weeks. The efficacy of atomoxetine
      was evaluated by using the Aberrant Behavior Checklist (ABC) to rate ADHD
      symptoms at baseline, week 6, and week 10. The Clinical Global Impression
      Improvement (CGI-I) scale was used as secondary outcome to assess the overall
      improvement of the children's development at week 10. RESULTS: A total of 12
      children participated in this study. Although CGI-I scores showed improvement at
      week 10, the ABC hyperactivity subscale did not show a significant improvement of
      the ADHD symptoms at baseline (M = 33.89) compared to those at week 10 (M =
      31.78, p = .62). CONCLUSION: Atomoxetine did not benefit children with severe
      autistic disorder who have ADHD symptoms.

PMID- 20686101
TI  - Social media and family nursing: where is my tribe?

PMID- 20686102
TI  - Family nursing research for practice: the Finnish perspective.
AB  - This article summarizes the efforts of the Department of Nursing Science,
      University of Tampere, Finland, to advance knowledge about family nursing over
      the past 15 years. Definitions of family, family nursing, and family nursing
      science are offered. Programs of research include families' experiences of care
      received in health care settings, family violence and child maltreatment, and the
      psychometric development of instruments to assess family functioning and family
      health. Research is currently examining the effectiveness of family nursing
      interventions. Recommendations are offered to strengthen collaboration between
      family nursing researchers, educators, and practitioners at the local level and
      initiate greater collaboration between family researchers at the
      interdisciplinary and international levels.

PMID- 20686103
TI  - Developing a family-centered participatory action research project.
AB  - The purpose of this article is to illustrate strategies used to design and
      implement a family-centered, participatory action research (PAR) project to meet
      the asthma information needs identified by English-, Hmong-, and Spanish-speaking
      parents of preschool children with asthma enrolled in a multisite, urban Head
      Start program. PAR is an approach that encourages researchers and those who will
      benefit from the research (e.g., families and community leaders) to work together
      in all phases of the project. PAR projects involve two core components: a needs
      assessment and action plan development. PAR is rooted in the cultural tradition
      of the participants and builds on strengths and resources in the community.
      Actively involving family participants and community leaders in community-based
      PAR projects increases the likelihood of developing interventions and resources
      that are culturally relevant and address family needs.

PMID- 20686104
TI  - Families suffering with HIV/AIDS: what family nursing interventions are useful to
      promote healing?
AB  - The purpose of this clinical research project was to examine the usefulness of a
      family nursing intervention program offered to families experiencing illness
      suffering related to HIV/AIDS. The interventions were based on the Family
      Caregiving Model and the Illness Beliefs Model. Sixteen Thai families with one or
      more family members living with HIV/AIDS were offered three to four family
      clinical sessions by an advanced practice family nurse. The audiotaped family
      clinical sessions and field notes were analyzed using thematic analysis. The
      outcomes reported by families included a competence to manage illness care of
      family members experiencing HIV/AIDS, new meaning and purpose, improved family
      interaction, embraced facilitating beliefs and changed constraining beliefs, and
      a recognition of the family's strengths.

PMID- 20686105
TI  - Maternal predictors of behavioral problems among Mexican migrant farmworker
      children.
AB  - This study investigated the impact of maternal parenting factors on the emotional
      and behavioral health of Mexican Migrant Head Start children. Although the
      majority of children sampled in this study did not exhibit problematic behaviors,
      the findings concluded that children who demonstrated emotional and behavioral
      problems experienced a more rejecting maternal parenting style, greater parenting
      stress, and mothers reporting feelings of depression. Gender differences were
      found between the behavioral and emotional problems of sons and daughters.
      Surprisingly, years in the United States, maternal birthplace, income, education,
      and language spoken in the home were not associated with child behavioral
      problems.

PMID- 20686107
TI  - Multiplex analysis of age-related protein and lipid modifications in human
      Bruch's membrane.
AB  - Aging of the human retina is characterized by progressive pathology, which can
      lead to vision loss. This progression is believed to involve reactive metabolic
      intermediates reacting with constituents of Bruch's membrane, significantly
      altering its physiochemical nature and function. We aimed to replace a myriad of
      techniques following these changes with one, Raman spectroscopy. We used
      multiplexed Raman spectroscopy to analyze the age-related changes in 7 proteins,
      3 lipids, and 8 advanced glycation/lipoxidation endproducts (AGEs/ALEs) in 63
      postmortem human donors. We provided an important database for Raman spectra from
      a broad range of AGEs and ALEs, each with a characteristic fingerprint. Many of
      these adducts were shown for the first time in human Bruch's membrane and are
      significantly associated with aging. The study also introduced the previously
      unreported up-regulation of heme during aging of Bruch's membrane, which is
      associated with AGE/ALE formation. Selection of donors ranged from ages 32 to 92
      yr. We demonstrated that Raman spectroscopy can identify and quantify age-related
      changes in a single nondestructive measurement, with potential to measure age
      related changes in vivo. We present the first directly recorded evidence of the
      key role of heme in AGE/ALE formation.

PMID- 20686108
TI  - Is there a glass ceiling for highly cited scientists at the top of research
      universities?
AB  - University leaders aim to protect, shape, and promote the missions of their
      institutions. I evaluated whether top highly cited scientists are likely to
      occupy these positions. Of the current leaders of 96 U.S. high research activity
      universities, only 6 presidents or chancellors were found among the 4009 U.S.
      scientists listed in the ISIHighlyCited.com database. Of the current leaders of
      77 UK universities, only 2 vice-chancellors were found among the 483 UK
      scientists listed in the same database. In a sample of 100 top-cited clinical
      medicine scientists and 100 top-cited biology and biochemistry scientists, only 1
      and 1, respectively, had served at any time as president of a university. Among
      the leaders of 25 U.S. universities with the highest citation volumes, only 12
      had doctoral degrees in life, natural, physical or computer sciences, and 5 of
      these 12 had a Hirsch citation index m < 1.0. The participation of highly cited
      scientists in the top leadership of universities is limited. This could have
      consequences for the research and overall mission of universities.

PMID- 20686109
TI  - Shaping of terminal megakaryocyte differentiation and proplatelet development by
      sphingosine-1-phosphate receptor S1P4.
AB  - Megakaryocytes, which mature from hematopoietic progenitors in the bone marrow,
      further differentiate by reorganizing their cytoplasm into long proplatelet
      extensions that release platelets into the circulation. The molecular mechanisms
      underlying this highly dynamic cytoplasmic and cytoskeletal remodeling process
      are only poorly understood. Here we report that sphingosine 1-phosphate receptor
      4 (S1P(4)) is specifically up-regulated during the development of human
      megakaryocytes from progenitor cells and is expressed in mature murine
      megakaryocytes. Megakaryocytes generated from S1P(4)-deficient murine bone marrow
      showed atypical and reduced formation of proplatelets in vitro. The recovery of
      platelet numbers after experimental thrombocytopenia was significantly delayed in
      S1p4(-/-) mice. Remarkably, overexpression and stimulation of S1P(4) in human
      erythroleukemia HEL cells promoted endomitosis, formation of cytoplasmic
      extensions, and subsequent release of platelet-like particles. These observations
      indicate that S1P(4) is involved in shaping the terminal differentiation of
      megakaryocytes.

PMID- 20686110
TI  - UV radiation, vitamin D, and multiple sclerosis.

PMID- 20686113
TI  - Gene targeting by homologous recombination in mouse zygotes mediated by zinc
      finger nucleases.
AB  - Gene targeting by homologous recombination in embryonic stem cells is extensively
      used to generate specific mouse mutants. However, most mammalian species lack
      tools for targeted gene manipulation. Since double-strand breaks strongly
      increase the rate of homologous recombination at genomic loci, we explored
      whether gene targeting can be directly performed in zygotes by the use of zinc
      finger nucleases. Here we report that gene targeting is achieved in 1.7-4.5% of
      murine one-cell embryos upon the coinjection of targeting vectors with zinc
      finger nucleases, without preselection. These findings enable the manipulation of
      the mammalian germ line in a single step in zygotes, independent of ES cells.

PMID- 20686112
TI  - Global phosphorylation analysis of beta-arrestin-mediated signaling downstream of
      a seven transmembrane receptor (7TMR).
AB  - beta-Arrestin-mediated signaling downstream of seven transmembrane receptors
      (7TMRs) is a relatively new paradigm for signaling by these receptors. We
      examined changes in protein phosphorylation occurring when HEK293 cells
      expressing the angiotensin II type 1A receptor (AT1aR) were stimulated with the
      beta-arrestin-biased ligand Sar(1), Ile(4), Ile(8)-angiotensin (SII), a ligand
      previously found to signal through beta-arrestin-dependent, G protein-independent
      mechanisms. Using a phospho-antibody array containing 46 antibodies against
      signaling molecules, we found that phosphorylation of 35 proteins increased upon
      SII stimulation. These SII-mediated phosphorylation events were abrogated after
      depletion of beta-arrestin 2 through siRNA-mediated knockdown. We also performed
      an MS-based quantitative phosphoproteome analysis after SII stimulation using a
      strategy of stable isotope labeling of amino acids in cell culture (SILAC). We
      identified 1,555 phosphoproteins (4,552 unique phosphopeptides), of which 171
      proteins (222 phosphopeptides) showed increased phosphorylation, and 53 (66
      phosphopeptides) showed decreased phosphorylation upon SII stimulation of the
      AT1aR. This study identified 38 protein kinases and three phosphatases whose
      phosphorylation status changed upon SII treatment. Using computational
      approaches, we performed system-based analyses examining the beta-arrestin
      mediated phosphoproteome including construction of a kinase-substrate network for
      beta-arrestin-mediated AT1aR signaling. Our analysis demonstrates that beta
      arrestin-dependent signaling processes are more diverse than previously
      appreciated. Notably, our analysis identifies an AT1aR-mediated cytoskeletal
      reorganization network whereby beta-arrestin regulates phosphorylation of several
      key proteins, including cofilin and slingshot. This study provides a system-based
      view of beta-arrestin-mediated phosphorylation events downstream of a 7TMR and
      opens avenues for research in a rapidly evolving area of 7TMR signaling.

PMID- 20686115
TI  - Modulation of human neutrophil survival and antigen expression by activated CD4+
      and CD8+ T cells.
AB  - Neutrophils and T cells often co-infiltrate pathological tissues, which suggests
      that these 2 cell types may interact with each other. Over the years, in vitro
      studies have demonstrated that neutrophils and T cells are capable of modulating
      each other's responses. However, few studies have examined the cross-talk between
      human neutrophils and CD8+ T cells, although murine models clearly show the
      critical role of their interaction in bacterial infections and cancer. Herein, we
      evaluated the interaction between human neutrophils and CD8+ T cells in a
      coculture system using highly purified cell preparations and compared the
      responses to ones from cocultures of neutrophils and CD4+ T cells. We report that
      anti-CD3-activated CD4+ and more potently, anti-CD3-activated CD8+ T cells
      modulate apoptosis and expression of activation markers by neutrophils, and
      neutrophils have no or little effect on T cell survival, expression of surface
      markers, and cytokine release. The observed effects of CD8+ T cells on
      neutrophils were mainly attributable to the release of TNF-alpha, IFN-gamma, and
      GM-CSF, and the effects of CD4+ T cells involved IFN-gamma and GM-CSF production.
      This study expands our knowledge of the molecular bases, whereby human CD4+ and
      CD8+ T cells modulate neutrophil survival and antigen expression.

PMID- 20686114
TI  - Imaging decreased brain docosahexaenoic acid metabolism and signaling in
      iPLA(2)beta (VIA)-deficient mice.
AB  - Ca(2+)-independent phospholipase A(2)beta (iPLA(2)beta) selectively hydrolyzes
      docosahexaenoic acid (DHA, 22:6n-3) in vitro from phospholipid. Mutations in the
      PLA2G6 gene encoding this enzyme occur in patients with idiopathic
      neurodegeneration plus brain iron accumulation and dystonia-parkinsonism without
      iron accumulation, whereas mice lacking PLA2G6 show neurological dysfunction and
      neuropathology after 13 months. We hypothesized that brain DHA metabolism and
      signaling would be reduced in 4-month-old iPLA(2)beta-deficient mice without
      overt neuropathology. Saline or the cholinergic muscarinic M(1,3,5) receptor
      agonist arecoline (30 mg/kg) was administered to unanesthetized iPLA(2)beta(-/-),
      iPLA(2)beta(+/-), and iPLA(2)beta(+/+) mice, and [1-(14)C]DHA was infused
      intravenously. DHA incorporation coefficients k* and rates J(in), representing
      DHA metabolism, were determined using quantitative autoradiography in 81 brain
      regions. iPLA(2)beta(-/-) or iPLA(2)beta(+/-) compared with iPLA(2)beta(+/+) mice
      showed widespread and significant baseline reductions in k* and J(in) for DHA.
      Arecoline increased both parameters in brain regions of iPLA(2)beta(+/+) mice but
      quantitatively less so in iPLA(2)beta(-/-) and iPLA(2)beta(+/-) mice. Consistent
      with iPLA(2)beta's reported ability to selectively hydrolyze DHA from
      phospholipid in vitro, iPLA(2)beta deficiency reduces brain DHA metabolism and
      signaling in vivo at baseline and following M(1,3,5) receptor activation.
      Positron emission tomography might be used to image disturbed brain DHA
      metabolism in patients with PLA2G6 mutations.

PMID- 20686116
TI  - PPARgamma modulated inflammatory response of human dendritic cell subsets to
      engulfed apoptotic neutrophils.
AB  - The means of how phagocytes handle apoptotic cells has a great impact on the
      outcome of immune responses. Here, we show that phagocytosis of allogeneic,
      apoptotic neutrophils by human monocyte-derived DCs is slow and less efficient
      than that of macrophages, and CD1a(-) DCs are more active in the engulfment of
      apoptotic neutrophils than CD1a(+) DCs. Blocking DC-SIGN function partially
      interferes with the uptake of apoptotic cells, and long-term interaction of
      apoptotic neutrophils with DCs makes them prone to proinflammatory cytokine
      responses. Engulfment of apoptotic cells sensitizes CD1a(-) DCs for high IL-8,
      TNF-alpha, IL-6, and CD1a(+) cells for IL-12 and IL-10 cytokine secretion
      elicited by additional inflammatory stimuli, which also result in the
      polarization of autologous T lymphocytes to Th1 effector cells. Ligand-induced
      activation of PPARgamma by RSG results in enhanced phagocytosis, but the
      proinflammatory response and the capacity to trigger Th1 cell activation of CD1a(
      ) DCs are not enhanced. These results demonstrate that DCs are able to respond to
      allogeneic, apoptotic neutrophils with inflammatory cytokines and T cell
      responses in a subtype-specific manner that is modulated by the anti-inflammatory
      effects of PPARgamma.

PMID- 20686117
TI  - How I treat patients with thrombotic thrombocytopenic purpura: 2010.
AB  - Thrombotic thrombocytopenic purpura (TTP) is the common name for adults with
      microangiopathic hemolytic anemia, thrombocytopenia, with or without neurologic
      or renal abnormalities, and without another etiology; children without renal
      failure are also described as TTP. The diagnosis of TTP is an indication for
      plasma exchange treatment, but beginning treatment requires sufficient confidence
      in the diagnosis to justify the risk of plasma exchange complications.
      Documentation of a severe deficiency of plasma ADAMTS13 activity, defined as less
      than 10% of normal, is not essential for the diagnosis of TTP. Some patients
      without severe ADAMTS13 deficiency may benefit from plasma exchange treatment; in
      addition, some patients with severe ADAMTS13 deficiency may subsequently be
      diagnosed with another cause for their clinical features. However, severe
      acquired ADAMTS13 deficiency does define a subgroup of patients who appear to
      benefit from treatment with corticosteroids and other immunosuppressive agents in
      addition to plasma exchange but who have a high risk for relapse. Approximately
      80% of patients survive their acute episode, a survival rate that has not changed
      since the introduction of plasma exchange treatment. Although recovery may appear
      to be complete, many patients have persistent minor cognitive abnormalities. More
      effective as well as safer treatment for TTP is needed.

PMID- 20686118
TI  - c-myb supports erythropoiesis through the transactivation of KLF1 and LMO2
      expression.
AB  - The c-myb transcription factor is highly expressed in immature hematopoietic
      cells and down-regulated during differentiation. To define its role during the
      hematopoietic lineage commitment, we silenced c-myb in human CD34(+)
      hematopoietic stem/progenitor cells. Noteworthy, c-myb silencing increased the
      commitment capacity toward the macrophage and megakaryocyte lineages, whereas
      erythroid differentiation was impaired, as demonstrated by clonogenic assay,
      morphologic and immunophenotypic data. Gene expression profiling and
      computational analysis of promoter regions of genes modulated in c-myb-silenced
      CD34(+) cells identified the transcription factors Kruppel-Like Factor 1 (KLF1)
      and LIM Domain Only 2 (LMO2) as putative targets, which can account for c-myb
      knockdown effects. Indeed, chromatin immunoprecipitation and luciferase reporter
      assay demonstrated that c-myb binds to KLF1 and LMO2 promoters and transactivates
      their expression. Consistently, the retroviral vector-mediated overexpression of
      either KLF1 or LMO2 partially rescued the defect in erythropoiesis caused by c
      myb silencing, whereas only KLF1 was also able to repress the megakaryocyte
      differentiation enhanced in Myb-silenced CD34(+) cells. Our data collectively
      demonstrate that c-myb plays a pivotal role in human primary hematopoietic
      stem/progenitor cells lineage commitment, by enhancing erythropoiesis at the
      expense of megakaryocyte diffentiation. Indeed, we identified KLF1 and LMO2
      transactivation as the molecular mechanism underlying Myb-driven erythroid versus
      megakaryocyte cell fate decision.

PMID- 20686119
TI  - Allogeneic hematopoietic cell transplantation for hematologic malignancy:
      relative risks and benefits of double umbilical cord blood.
AB  - Effectiveness of double umbilical cord blood (dUCB) grafts relative to
      conventional marrow and mobilized peripheral blood from related and unrelated
      donors has yet to be established. We studied 536 patients at the Fred Hutchinson
      Cancer Research Center and University of Minnesota with malignant disease who
      underwent transplantation with an human leukocyte antigen (HLA)-matched related
      donor (MRD, n = 204), HLA allele-matched unrelated donor (MUD, n = 152) or 1
      antigen-mismatched unrelated adult donor (MMUD, n = 52) or 4-6/6 HLA matched dUCB
      (n = 128) graft after myeloablative conditioning. Leukemia-free survival at 5
      years was similar for each donor type (dUCB 51% [95% confidence interval (CI),
      41%-59%]; MRD 33% [95% CI, 26%-41%]; MUD 48% [40%-56%]; MMUD 38% [95% CI, 25%
      51%]). The risk of relapse was lower in recipients of dUCB (15%, 95% CI, 9%-22%)
      compared with MRD (43%, 95% CI, 35%-52%), MUD (37%, 95% CI, 29%-46%) and MMUD
      (35%, 95% CI, 21%-48%), yet nonrelapse mortality was higher for dUCB (34%, 95%
      CI, 25%-42%), MRD (24% (95% CI, 17%-39%), and MUD (14%, 95% CI, 9%-20%). We
      conclude that leukemia-free survival after dUCB transplantation is comparable
      with that observed after MRD and MUD transplantation. For patients without an
      available HLA matched donor, the use of 2 partially HLA-matched UCB units is a
      suitable alternative.

PMID- 20686120
TI  - Targeting TORC2 in multiple myeloma with a new mTOR kinase inhibitor.
AB  - Although preclinical work with rapalogs suggests potential in treatment of
      multiple myeloma (MM), they have been less successful clinically. These drugs
      allostearically inhibit the mammalian target of rapamycin kinase primarily
      curtailing activity of the target of rapamycin complex (TORC)1. To assess if the
      mammalian target of rapamycin within the TORC2 complex could be a better target
      in MM, we tested a new agent, pp242, which prevents activation of TORC2 as well
      as TORC1. Although comparable to rapamycin against phosphorylation of the TORC1
      substrates p70S6kinase and 4E-BP-1, pp242 could also inhibit phosphorylation of
      AKT on serine 473, a TORC2 substrate, while rapamycin was ineffective. pp242 was
      also more effective than rapamycin in achieving cytoreduction and apoptosis in MM
      cells. In addition, pp242 was an effective agent against primary MM cells in
      vitro and growth of 8226 cells in mice. Knockdown of the TORC2 complex protein,
      rictor, was deleterious to MM cells further supporting TORC2 as the critical
      target for pp242. TORC2 activation was frequently identified in primary specimens
      by immunostaining for AKT phosphorylation on serine 473. Potential mechanisms of
      up-regulated TORC2 activity in MM were stimulation with interleukin-6 or insulin
      like growth factor 1, and phosphatase and tensin homolog or RAS alterations.
      Combining pp242 with bortezomib led to synergistic anti-MM effects. These results
      support TORC2 as a therapeutic target in MM.

PMID- 20686121
TI  - Inhibition of erythropoiesis in malaria anemia: role of hemozoin and hemozoin
      generated 4-hydroxynonenal.
AB  - Severe malaria anemia is characterized by inhibited/altered erythropoiesis and
      presence of hemozoin-(HZ)-laden bone-marrow macrophages. HZ mediates peroxidation
      of unsaturated fatty acids and production of bioactive aldehydes such as 4
      hydroxynonenal (HNE). HZ-laden human monocytes inhibited growth of cocultivated
      human erythroid cells and produced HNE that diffused to adjacent cells generating
      HNE-protein adducts. Cocultivation with HZ or treatment with low micromolar HNE
      inhibited growth of erythroid cells interfering with cell cycle without
      apoptosis. After HZ/HNE treatment, 2 critical proteins in cell-cycle regulation,
      p53 and p21, were increased and the retinoblastoma protein, central regulator of
      G1-to-S-phase transition, was consequently hypophosphorylated, while GATA-1,
      master transcription factor in erythropoiesis was reduced. The resultant
      decreased expression of cyclin A and D2 retarded cell-cycle progression in
      erythroid cells and the K562 cell line. As a second major effect, HZ and HNE
      inhibited protein expression of crucial receptors (R): transferrinR1, stem cell
      factorR, interleukin-3R, and erythropoietinR. The reduced receptor expression and
      the impaired cell-cycle activity decreased the production of cells expressing
      glycophorin-A and hemoglobin. Present data confirm the inhibitory role of HZ,
      identify HNE as one HZ-generated inhibitory molecule and describe molecular
      targets of HNE in erythroid progenitors possibly involved in erythropoiesis
      inhibition in malaria anemia.

PMID- 20686122
TI  - Discrepancies in international normalized ratio results between instruments: a
      model to split the variation into subcomponents.
AB  - BACKGROUND: Observed differences between results obtained from comparison of
      instruments used to measure international normalized ratio (INR) have been higher
      than expected from the imprecision of the instruments. In this study the
      variation of these differences was divided into subcomponents, and each of the
      subcomponents was estimated. METHODS: Blood samples were collected at 4 different
      patient visits from each of 36 outpatients who were receiving warfarin treatment
      and were included in the study. INR was determined on 1 laboratory instrument
      (STA Compact(r)) and 3 point-of-care instruments (Simple Simon(r)PT,
      CoaguChek(r)XS, and INRatioTM). All 4 INR instruments were compared in pairs.
      Linear regression was used to correct for systematic deviations. The remaining
      variation of the differences was subdivided into between-subject, within-subject,
      and analytical variation in an ANOVA nested design. RESULTS: The mean difference
      between instruments varied between 1.0% and 14.3%. Between-subject variation of
      the differences (expressed as CV) varied between 3.3% and 7.4%, whereas within
      subject variation of the differences was approximately 5% for all 6 comparisons.
      The analytical imprecision of the differences varied between 3.8% and 8.6%.
      CONCLUSIONS: The differences in INR between instruments were subdivided into
      calibration differences, between- and within-subject variation, and analytical
      imprecision. The magnitude of each subcomponent was estimated. Within results for
      individual patients the difference in INR between 2 instruments varied over time.
      The reasons for the between- and within-subject variations of the differences can
      probably be ascribed to different patient-specific effects in the patient plasma.
      To minimize this variation in a monitoring situation, each site and patient
      should use results from only 1 type of instrument.

PMID- 20686124
TI  - Parkinson disease and down in the dumps: pumped or stumped?

PMID- 20686123
TI  - Genomic signatures of germline gene expression.
AB  - Transcribed regions in the human genome differ from adjacent intergenic regions
      in transposable element density, crossover rates, and asymmetric substitution and
      sequence composition patterns. We tested whether these differences reflect
      selection or are instead a byproduct of germline transcription, using publicly
      available gene expression data from a variety of germline and somatic tissues.
      Crossover rate shows a strong negative correlation with gene expression in
      meiotic tissues, suggesting that crossover is inhibited by transcription. Strand
      biased composition (G+T content) and A -> G versus T -> C substitution asymmetry
      are both positively correlated with germline gene expression. We find no evidence
      for a strand bias in allele frequency data, implying that the substitution
      asymmetry reflects a mutation rather than a fixation bias. The density of
      transposable elements is positively correlated with germline expression,
      suggesting that such elements preferentially insert into regions that are
      actively transcribed. For each of the features examined, our analyses favor a
      nonselective explanation for the observed trends and point to the role of
      germline gene expression in shaping the mammalian genome.

PMID- 20686125
TI  - Regional patterns of brain tissue loss associated with depression in Parkinson
      disease.
AB  - OBJECTIVE: To investigate, using MRI and voxel-based morphometry (VBM), whether
      specific patterns of gray matter (GM) and white matter (WM) loss are associated
      with depression in patients with Parkinson disease (PD). METHODS: Forty patients
      with PD and 26 healthy subjects were studied. Patients were diagnosed with
      depression using DSM-IV criteria. The Hamilton Depression Rating Scale (HDRS) was
      administered to patients. The topographic distribution of brain tissue loss in
      patients with PD and controls was assessed using VBM as implemented in
      Statistical Parametric Mapping (SPM5). RESULTS: Twenty-four patients with PD were
      diagnosed as nondepressed (PD-NDep) and 16 as having depression (PD-Dep). Patient
      groups were similar in terms of clinical findings, except for the HDRS score (p <
      0.001). Compared to controls, patients with PD showed common GM loss in the right
      anterior cingulate (AC) cortex and insula, and in the left middle frontal and
      angular gyri (p < 0.001). No regions of WM loss common to PD-NDep and PD-Dep
      patients relative to healthy controls were found. PD-Dep vs PD-NDep patients
      showed WM loss in the right AC bundle and inferior orbitofrontal (OF) region (p <
      0.001). In patients with PD, HDRS score correlated with WM loss in the right
      inferior OF region (r = -0.51, p < 0.05). CONCLUSIONS: Tissue loss in several WM
      regions within the cortical-limbic network occurs in PD-Dep vs PD-NDep patients.
      Such pattern of brain atrophy overlaps with key regions involved in major
      depressive disorders, suggesting an increased vulnerability of this neural
      circuit in PD. This may partially account for the high prevalence of depression
      in PD.

PMID- 20686126
TI  - Dendritic cells induce regulatory T cell proliferation through antigen-dependent
      and -independent interactions.
AB  - Regulatory T cells (Tregs) are a subset of T cells with suppressive function that
      protect the host from autoimmunity and prevent excessive immunopathology.
      Functional Tregs must be present throughout life to provide continuous protection
      for the host. Despite the intense study of this lineage, the mechanisms by which
      Tregs are maintained in the steady-state remain incompletely understood. In this
      study, we investigated the role of dendritic cells (DCs) in the control of Treg
      proliferation. In the absence of overt TCR stimulation, we found that DCs induce
      polyclonal Treg division in murine splenocyte cultures. In vivo expansion of DCs
      also correlated with polyclonal Treg expansion. DC-induced Treg division required
      IL-2, which was provided by conventional CD4(+) T cells through an MHC class II
      (MHC II)-dependent interaction with DCs. Provision of exogenous IL-2 obviated the
      need for conventional CD4(+) T cells in the induction of Treg proliferation, but
      this process still required a contact-dependent but MHC II-independent
      interaction between DCs and Tregs. Although Treg division could occur in the
      absence of MHC II expression by DCs, direct stimulation of Tregs by cognate
      Ag/MHC II complexes enhanced IL-2-induced Treg proliferation. These data
      demonstrate that DCs coordinate the interactions that are necessary to initiate
      polyclonal Treg proliferation.

PMID- 20686127
TI  - Heat shock protein 90 mediates efficient antigen cross presentation through the
      scavenger receptor expressed by endothelial cells-I.
AB  - Ag cross presentation is an important mechanism for CD8(+) T cell activation by
      APCs. We have investigated mechanisms involved in heat shock protein 90 (Hsp90)
      chaperone-mediated cross presentation of OVA-derived Ags. Hsp90-OVA peptide
      complexes bound to scavenger receptor expressed by endothelial cells (SREC-I) on
      the surface of APCs. SREC-I then mediated internalization of Hsp90-OVA
      polypeptide complexes through a Cdc42-regulated, dynamin-independent endocytic
      pathway known as the GPI-anchored protein-enriched early endosomal compartment to
      recycling endosomes. Peptides that did not require processing could then be
      loaded directly onto MHC class I in endosomes, whereas longer peptides underwent
      endosomal and cytosomal processing by aminopeptidases and proteases. Cross
      presentation of Hsp90-chaperoned peptides through this pathway to CD8(+) T cells
      was highly efficient compared with processing of free polypeptides. In addition,
      Hsp90 also activated c-Src kinase associated with SREC-I, an activity that we
      determined to be required for effective cross presentation. Extracellular Hsp90
      can thus convey antigenic peptides through an efficient endocytosis pathway in
      APCs and facilitate cross presentation in a highly regulated manner.

PMID- 20686129
TI  - Mice producing less reactive oxygen species are relatively resistant to collagen
      glycopeptide vaccination against arthritis.
AB  - The bottleneck for the induction of collagen-induced arthritis in mice is the
      recognition of immunodominant type II collagen (CII) peptide (CII259-273) bound
      to the MHC class II molecule A(q). We have shown previously that the
      posttranslationally glycosylated lysine at position 264 in this epitope is of
      great importance for T cell recognition and tolerance induction to CII as well as
      for arthritis development. The Ncf1 gene, controlling oxidative burst, has been
      shown to play an important role for immune tolerance to CII. To investigate the
      effect of oxidation on the efficiency of immune-specific vaccination with MHC
      class II/glycosylated-CII peptide complexes, we used Ncf1 mutated mice. We
      demonstrate that normal reactive oxygen species (ROS) levels contribute to the
      establishment of tolerance and arthritis protection, because only mice with a
      functional oxidative burst were completely protected from arthritis after
      administration of the glycosylated CII259-273 peptide in complex with MHC class
      II. Transfer of T cells from vaccinated mice with functional Ncf1 protein
      resulted in strong suppression of clinical signs of arthritis in B10.Q mice,
      whereas the Ncf1 mutated mice as recipients had a weaker suppressive effect,
      suggesting that ROS modified the secondary rather than the primary immune
      response. A milder but still significant effect was also observed in ROS
      deficient mice. During the primary vaccination response, regulatory T cells,
      upregulation of negative costimulatory molecules, and increased production of
      anti-inflammatory versus proinflammatory cytokines in both Ncf1 mutated and wild
      type B10.Q mice was observed, which could explain the vaccination effect
      independent of ROS.

PMID- 20686130
TI  - Reciprocal functional modulation of the activation of T lymphocytes and
      fibroblasts derived from human solid tumors.
AB  - Fibroblasts are a dominant cell type in most human solid tumors. The possibility
      that fibroblasts have the capacity to interact with and modulate the function of
      tumor-associated T lymphocytes makes them a potential therapeutic target. To
      address this question, primary cultures of fibroblasts derived from human lung
      tumors were established and cultured with T cells derived from the same tumor.
      The tumor fibroblasts significantly enhance the production of IFN-gamma and IL
      17A by the tumor-associated T cells following a CD3/CD28-induced activation of
      the T cells. This enhancement was fibroblast cell dose-dependent and did not
      require direct contact between the two cell types. Tumor-associated fibroblast
      conditioned media similarly enhanced both IFN-gamma and IL-17A in activated T
      cells, and this enhancement was significantly reduced by Abs to IL-6. Conditioned
      media derived from activated lymphocyte cultures significantly enhanced IL-6
      production by tumor fibroblasts. A similar enhancement of IFN-gamma and IL-17A
      was observed when activated T cells from a normal donor were cultivated with skin
      fibroblasts derived from the same donor. These results establish that fibroblasts
      and autologous lymphocytes, whether derived from the tumor microenvironment or
      from nonmalignant tissues, have the capacity to reciprocally interact and
      modulate function. In contrast to other reports, fibroblasts are shown to have an
      immunostimulatory effect upon activated T lymphocytes. The ability of fibroblasts
      to enhance two T cell cytokines known to have an impact upon tumor progression
      suggests that fibroblasts play an important role in tumor pathogenesis that could
      be exploited therapeutically.

PMID- 20686128
TI  - B7-H1-dependent sex-related differences in tumor immunity and immunotherapy
      responses.
AB  - CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) are immunopathogenic in cancers
      by impeding tumor-specific immunity. B7-homologue 1 (B7-H1) (CD274) is a
      cosignaling molecule with pleiotropic effects, including hindering antitumor
      immunity. In this study, we demonstrate sex-dependent, B7-H1-dependent
      differences in tumor immunity and response to immunotherapy in a hormone
      independent cancer, murine B16 melanoma. Antitumor immunity was better in B7-H1(
      /-) females versus males as a result of reduced regulatory T cell function in the
      B7-H1(-/-) females, and clinical response following B7-H1 blockade as tumor
      immunotherapy was significantly better in wild-type females than in males, owing
      to greater B7-H1 blockade-mediated reduction of Treg function in females. Wild
      type female Tregs expressed significantly lower B7-H1 versus males but were
      insensitive to estrogen in vitro. Female B7-H1(-/-) Tregs were exquisitely
      sensitive to estrogen-mediated functional reduction in vitro, suggesting that B7
      H1 effects occur before terminal Treg differentiation. Immune differences were
      independent of known B7-H1 ligands. Sex-dependent immune differences are seldom
      considered in designing immune therapy or interpreting immunotherapy treatment
      results. Our data demonstrate that sex is an important variable in tumor
      immunopathogenesis and immunotherapy responses through differential Treg function
      and B7-H1 signaling.

PMID- 20686131
TI  - Substance use disorders: do males and females have differential vulnerability?

PMID- 20686132
TI  - A hypothesized role for dendritic remodeling in the etiology of mood and anxiety
      disorders.
AB  - An elegant theory that links hippocampal neurogenesis to mood and anxiety
      disorders and to the mechanism of action of antidepressant drugs has gained
      widespread attention. However, depression and anxiety disorders involve multiple
      areas of the brain, such as the amygdala and prefrontal cortex, where
      neurogenesis does not appear to occur in the adult mammalian brain. A
      complementary theory is proposed here in which neurogenesis is seen as an
      epiphenomenon of a more widespread alteration in dendritic length and spine
      number. According to this theory, exposure to chronic stress and stressful life
      events increases excitotoxic glutamatergic neurotransmission in multiple brain
      areas. To protect neurons from consequent apoptosis, dendrites retract and spine
      number decreases, thus limiting the number of exposed glutamate receptors. Drugs
      that reduce glutamatergic neurotransmission under these circumstances, many of
      which have already been shown helpful in treating mood and anxiety disorders, may
      prevent this dendritic retraction and thus protect synaptic connections
      throughout the brain.

PMID- 20686133
TI  - Asymmetrical contribution of brain structures to treatment-resistant depression
      as illustrated by effects of right subgenual cingulum stimulation.
AB  - Major depressive disorder is one of the most common psychiatric disorders, with a
      worldwide lifetime prevalence rate of 10%-20% in women and a slightly lower rate
      in men. While many patients are successfully treated using established
      therapeutic strategies, a significant percentage of patients fail to respond.
      This report describes the successful recovery of a previously treatment-resistant
      patient following right unilateral deep brain stimulation of Brodmann's area 25.
      Current therapeutic approaches to treatment-resistant patients are reviewed in
      the context of this case with an emphasis on the role of the right and left
      hemispheres in mediating disease pathogenesis and clinical recovery.

PMID- 20686135
TI  - Correlates of apathy in Huntington's disease.
AB  - The authors aim to study prevalence and clinical correlates of apathy in
      Huntington's disease. Apathy was defined as an Apathy Scale score > or =14 points
      in 152 Huntington's disease mutation carriers and 56 noncarriers. Correlates of
      apathy were analyzed cross-sectionally in mutation carriers using multivariable
      logistic regression analysis. Forty-nine (32%) Huntington's disease mutation
      carriers showed apathy compared to none of the noncarriers. After exclusion of 10
      depressed patients, apathy was independently associated with male sex, worse
      global functioning, and higher use of neuroleptics and benzodiazepines.

PMID- 20686134
TI  - Neuropathic pain syndrome displayed by malingerers.
AB  - Among 237 patients communicating chronic pain, associated with sensory-motor and
      "autonomic" displays, qualifying taxonomically for neuropathic pain, there were
      16 shown through surveillance to be malingerers. When analyzed through
      neurological methods, their profile was characteristically atypical. There were
      no objective equivalents of peripheral or central processes impairing nerve
      impulse transmission. In absence of medical explanation, all 16 had been
      adjudicated, by default, the label complex regional pain syndrome (CRPS). The
      authors emphasize that CRPS patients may not only harbor unrecognized pathology
      ("lesion") of the nervous system (CRPS II), hypothetical central neuronal
      "dysfunction" (CRPS I), or conversion disorder, but may display a recognizable
      simulated illness without neuropsychiatric pathology.

PMID- 20686136
TI  - Neuropsychological consequence of soccer play in adolescent U.K. School team
      soccer players.
AB  - To assess mild head injury effects in adolescent soccer players,
      neuropsychological performance across school team soccer players, rugby players
      and noncontact sport players was assessed in a quasi-experimental cross-sectional
      design. One hundred eighty-five males were tested (ages 13-16; response rate 55%)
      and 86 contributed data to the analyses after exclusion for recent concussion and
      overlapping sports participation. Soccer players showed lower premorbid
      intellectual functioning, but neither soccer players nor rugby players showed
      neuropsychological decrement compared with noncontact sport players. Cumulative
      heading did not predict neuropsychological performance. While no specific
      attribute of soccer was linked with neuropsychological impairment, head injury
      predicted reduced attention for all participants.

PMID- 20686137
TI  - Nonclinical obsessive-compulsive symptoms and executive functions in
      schizophrenia.
AB  - The impact of nonclinical obsessive-compulsive symptoms (OCS) on
      neuropsychological functioning in schizophrenia has received little
      investigation. The authors evaluated whether severity and subtype of OCS are
      associated with executive functioning in schizophrenia. Twenty-nine patients with
      schizophrenia and 32 healthy comparison subjects completed questionnaire and
      performance-based measures of executive functioning. Overall OCS severity in
      patients was associated with poorer monitoring and cognitive flexibility.
      Obsessing, hoarding, and checking were related to poorer executive functioning in
      daily life. Performance-based scores showed few correlations with OCS. Findings
      indicate that severity of nonclinical OCS subtypes contributes to the
      heterogeneity of executive functions in schizophrenia.

PMID- 20686138
TI  - White matter correlates of apathy in HIV-positive subjects: a diffusion tensor
      imaging study.
AB  - Apathy is commonly reported by patients infected with HIV. No previous work has
      assessed the relationship between white matter and apathy in HIV. The authors
      aimed to determine whether apathy in HIV reflects a direct effect of the virus on
      subcortical brain regions or a secondary neuropsychiatric symptom. Thirteen HIV+
      participants with apathy, 13 HIV+ participants with no apathy, and 10 healthy
      comparison subjects were examined using diffusion tensor imaging in the region of
      the anterior cingulate and corpus callosum. Results of the study confirmed the
      hypothesis which anticipated changes associated with apathy in white matter
      tracts that relay through the medial prefrontal cortex.

PMID- 20686139
TI  - Immune activation and neuropsychiatric symptoms in HIV infection.
AB  - This study examined the role of biological processes in the development of
      specific neuropsychiatric complications in HAART-naive adults with HIV/AIDS.
      Depressive symptoms were modestly associated with elevated IL-6 mRNA expression
      (r(s)=0.40, p<0.05) even after removing the influences of other subjective
      complaints (pr=0.39, p<0.05). Elevated serum neopterin was strongly associated
      with depressive symptoms in individuals taking antidepressants (r(s)=0.83,
      p<0.001), though the association was nullified in those not on antidepressants
      (r(s)=-0.25, p>0.05). Mean neopterin levels were higher in the depressed as
      compared with nondepressed group but only for those taking antidepressants
      (F=45.66, df=1, 11, p<0.001). Neuropsychological impairment was not associated
      with the biological markers. These findings suggest that systemic immune markers
      (like neopterin) may be useful in differentiating treatment-resistant individuals
      at greater risk of developing chronic depression.

PMID- 20686141
TI  - Feeling down: idiom or nature?
AB  - Different emotions activate different parts of the brain, and different parts of
      the brain direct actions-intentions as well as attention (AIA) to different
      portions of space. This pilot study attempted to learn how different emotions
      elicited by emotional memories altered the voluntary spatial allocation of AIA.
      Twenty normal participants were asked to mark a large sheet of paper in any place
      of their choosing following recollection of seven types of emotional memories.
      The results suggest that different emotional memories-experiences can influence
      the spatial allocation of AIA with positive emotional memories inducing a distal
      or superior bias and sad memories inducing a proximal or inferior bias. Although
      these results support the hypotheses that emotions can influence the spatial
      direction of AIA, these preliminary results need replication and further
      exploration.

PMID- 20686140
TI  - Relationship between cognitive status at admission and incident delirium in older
      medical inpatients.
AB  - To evaluate the relationship between cognitive status and incident delirium, 291
      geriatric patients on internal medicine wards were evaluated on admission with
      the Mini-Mental State Examination (MMSE) and Confusion Assessment Method-Spanish.
      Those with incident delirium were assessed using the Delirium Rating Scale
      Revised-98 (DRS-R98). Delirium incidence was 11.7%, and 82 patients (28.2%) had
      cognitive deficits on MMSE. As cognitive impairment worsened, the risk for
      delirium increased linearly, and for each unit of MMSE worsening the DRS-R98
      severity score worsened 0.4 points (F=5.39, df=1, p=0.027). Optimal MMSE cutoff
      score from receiver-operating characteristic curve analysis was 24.5. Even mild
      cognitive deficits increase delirium risk and severity.

PMID- 20686142
TI  - A study of herbal remedies for memory complaints.
AB  - This study explored the approach to marketing herbal substances and the specific
      remedies being sold for the treatment of memory complaints. Gingko and
      phosphatidylcholine/phosphatidylserine were most frequently recommended, often in
      combinations with many other substances. Counseling regarding toxicity is nil.

PMID- 20686143
TI  - Altered Attribution of Intention in Tourette's Syndrome.
AB  - Core symptoms of Tourette's syndrome are assumed to result from inhibitory
      dysfunction, which could also impair theory of mind. Here the authors report
      evidence for theory of minddifficulties: patients exhibit deficits in recognizing
      faux pas and understanding intentionality.

PMID- 20686144
TI  - Successful treatment with amisulpride for poststroke psychosis.

PMID- 20686145
TI  - Improving phonological dyslexia using electrical stimulation in the articulatory
      system.

PMID- 20686146
TI  - Ciproterone effect on compulsive masturbation in a frontotemporal dementia
      patient.

PMID- 20686147
TI  - Aripiprazole in the treatment of olanzapine-resistant psychotic and motor
      symptoms of Huntington's disease.

PMID- 20686148
TI  - Paroxysmal nonkinesigenic dyskinesia with depression treated by bilateral
      electroconvulsive therapy.

PMID- 20686149
TI  - Primary bilateral thalamic astrocytoma presenting with head tremor, ataxia, and
      dementia.

PMID- 20686150
TI  - PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated With
      Streptococcal Infection): a case report.

PMID- 20686151
TI  - Levodopa addiction and factitious disorder in a patient with idiopathic
      Parkinson's disease.

PMID- 20686152
TI  - Deliberate insulin underdosing and omission should be included in DSM-V criteria
      for bulimia nervosa.

PMID- 20686153
TI  - Dopamine deficiency may lead to capgras syndrome in Parkinson's disease with
      dementia.

PMID- 20686154
TI  - Alice in wonderland syndrome in major depressive disorder.

PMID- 20686155
TI  - Catatonia after right temporal lobe resection.

PMID- 20686156
TI  - Diagnostic pitfalls in a patient with posttraumatic exaggerated startle response
      and mutistic stupor.

PMID- 20686157
TI  - Allopurinol may prolong seizure duration on electroconvulsive therapy: a case
      report.

PMID- 20686158
TI  - Is methylphenidate-induced chorea responsive to chlorpromazine?

PMID- 20686159
TI  - Mirtazapine-associated urinary retention.

PMID- 20686160
TI  - Possible rabbit syndrome with amisulpride.

PMID- 20686161
TI  - Amisulpride may worsen dyskinesia and trigger new-onset dyskinetic movements.

PMID- 20686162
TI  - Suicidal ideation secondary to sodium oxybate.

PMID- 20686163
TI  - Pisa syndrome during amisulpride treatment.

PMID- 20686164
TI  - Tadalafil-induced transient global amnesia.

PMID- 20686165
TI  - Low-dose trazodone-related drug eruption.

PMID- 20686166
TI  - Comment on "Essential Role of IL-17A in the formation of a mycobacterial
      infection-induced granuloma in the lung".

PMID- 20686167
TI  - Much ado about adenosine: adenosine synthesis and function in regulatory T cell
      biology.
AB  - Recent studies have reported that adenosine is a significant mediator of
      regulatory T cell (Treg) function. Indeed, activation of the adenosine receptor
      subtypes expressed by a broad range of immune and inflammatory cells attenuates
      inflammation in several disease models. This anti-inflammatory response is
      associated with an increase in intracellular cAMP that inhibits cytokine
      responses of many immune/inflammatory cells, including T cells and APCs. Thus,
      adenosine produced by Tregs can provide a paracrine feedback that shapes the host
      response following an immunologic provocation. This review discusses the evidence
      that adenosine is an integral part of Treg biology and presents some of the
      mechanisms that may account for its contribution to the resolution of
      inflammation and the regulation of the immune/inflammatory cell phenotype.

PMID- 20686169
TI  - Gas exchange kinetics in obese adolescents. Inferences on exercise tolerance and
      prescription.
AB  - A functional evaluation of skeletal muscle oxidative metabolism was performed in
      a group of obese adolescents (OB). The various components of pulmonary O(2)
      uptake (Vo(2)) kinetics were evaluated during 10-min constant-load exercises
      (CLE) on a cycloergometer at different percentages of Vo(2max). The relationships
      of these components with the gas exchange threshold (GET) were determined.
      Fourteen male OB [age 16.5 +/- 1.0 (SD) yr, body mass index 34.5 +/- 3.1 kg.m(
      2)] and 13 normal-weight, age-matched nonathletic male volunteers (control group)
      were studied. The time-constant (tauf) of the fundamental component and the
      presence, pattern, and relative amplitude of the slow component of Vo(2) kinetics
      were determined at 40, 60, and 80% of Vo(2max), previously estimated during an
      incremental test. Vo(2max) (l/min) was similar in the two groups. GET was lower
      in OB (55.7 +/- 6.7% of Vo(2max)) than in control (65.1 +/- 5.2%) groups. The
      tauf was higher in OB subjects, indicating a slower fundamental component. At CLE
      60% (above GET in OB subjects, below GET in control subjects) a slow component
      was observed in nine out of fourteen OB subjects, but none in the control group.
      All subjects developed a slow component at CLE 80% (above GET in both OB and
      control). Twelve OB subjects did not complete the 10-min CLE 80% due to voluntary
      exhaustion. In nine OB subjects, the slow component was characterized by a linear
      increase in Vo(2) as a function of time. The slope of this increase was inversely
      related to the time to exhaustion. The above findings should negatively affect
      exercise tolerance in obese adolescents and suggest an impairment of skeletal
      muscle oxidative metabolism. Also in obese adolescents, exercise evaluation and
      prescription at submaximal loads should be done with respect to GET and not at a
      given percentage of Vo(2max).

PMID- 20686168
TI  - Energy expenditure in obesity-prone and obesity-resistant rats before and after
      the introduction of a high-fat diet.
AB  - While most rats gain weight when placed on a high-fat diet (HFD), some strains
      resist HFD-induced weight gain. To maintain weight, obesity-resistant (OR) rats
      must either eat less than obesity-prone (OP) rats or increase total energy
      expenditure (TEE). To determine if changes in TEE predispose to or protect from
      weight gain, energy expenditure, energy intake, and weight gain were measured in
      male and female OP and OR rats consuming a low-fat diet (LFD) and for 5 days
      after switching to a HFD. After 5 days on a HFD, OP rats gained significantly
      more weight (male: 42.8 +/- 6.9 g, female: 25.5 +/- 3.0 g) than their OR
      counterparts (male: 24.0 +/- 7.5 g, female: 13.7 +/- 1.4 g). Both male and female
      rats significantly increased their energy intake when transitioned to the HFD,
      and TEE increased modestly in all groups. Compared with female OP rats, female OR
      rats had a significantly greater increase in TEE on the HFD. This was due to an
      increase in both resting and nonresting energy expenditure. In contrast, the
      effect of the HFD in males was minor. TEE was also measured in female rats
      consuming a HFD, pair fed to LFD calories. The increase in TEE of pair-fed female
      OR rats was substantially less than what was seen in the HFD ad libitum
      condition. Physical activity was also measured in female rats. There was no
      evidence that increases in physical activity were the cause of the increased TEE
      seen in female OR rats consuming a HFD. These results suggest that resistance to
      HFD-induced weight gain in female OR rats may be due in part to an increase in
      TEE and a greater reliance on lipid as an energy source. Changes in TEE appear to
      be triggered by overconsumption of the HFD and not simply the diet composition.

PMID- 20686170
TI  - Increased renal alpha-epithelial sodium channel (ENAC) protein and increased ENAC
      activity in normal pregnancy.
AB  - Pregnancy-mediated sodium (Na) retention is required to provide an increase in
      plasma volume for the growing fetus. The mechanisms responsible for this Na
      retention are not clear. We first used a targeted proteomics approach and found
      that there were no changes in the protein abundance compared with virgin rats of
      the beta or gamma ENaC, type 3 Na(+)/H(+) exchanger (NHE3), bumetanide-sensitive
      cotransporter (NKCC2), or NaCl cotransporter (NCC) in mid- or late pregnancy. In
      contrast, we observed marked increases in the abundance of the alpha-ENaC
      subunit. The plasma volume increased progressively during pregnancy with the
      greatest plasma volume being evident in late pregnancy. ENaC inhibition abolished
      the difference in plasma volume status between virgin and pregnant rats. To
      determine the in vivo activity of ENaC, we conducted in vivo studies of rats in
      late pregnancy (days 18-20) and virgin rats to measure the natriuretic response
      to ENaC blockade (with benzamil). The in vivo activity of ENaC (U(Na)V
      postbenzamil-U(Na)V postvehicle) was markedly increased in late pregnancy, and
      this difference was abolished by pretreatment with the mineralocorticoid receptor
      antagonist, eplerenone. These findings demonstrate that the increased alpha-ENaC
      subunit of pregnancy is associated with an mineralocorticoid-dependent increase
      in ENaC activity. Further, we show that ENaC activity is a major contributor of
      plasma volume status in late pregnancy. These changes are likely to contribute to
      the renal sodium retention and plasma volume expansion required for an optimal
      pregnancy.

PMID- 20686171
TI  - Physiological characteristics of gastric contractions and circadian gastric
      motility in the free-moving conscious house musk shrew (Suncus murinus).
AB  - Although many studies have demonstrated the physiological action of motilin on
      the migrating motor complex, the precise mechanisms remain obscure. To obtain new
      insights into the mechanisms, we focused on the house musk shrew (Suncus murinus,
      suncus used as a laboratory name) as a small model animal for in vivo motilin
      study, and we studied the physiological characteristics of suncus
      gastrointestinal motility. Strain gauge transducers were implanted on the serosa
      of the gastric body and duodenum, and we recorded gastrointestinal contractions
      in the free-moving conscious suncus and also examined the effects of intravenous
      infusion of various agents on gastrointestinal motility. During the fasted state,
      the suncus stomach and duodenum showed clear migrating phase III contractions
      (intervals of 80-150 min) as found in humans and dogs. Motilin (bolus injection,
      100-300 ng/kg; continuous infusion, 10-100 ng.kg(-1).min(-1)) and erythromycin
      (80 MUg.kg(-1).min(-1)) induced gastric phase III contractions, and motilin
      injection also increased the gastric motility index in a dose-dependent manner (P
      < 0.05, vs. saline). Pretreatment with atropine completely abolished the motilin
      induced gastric phase III contractions. On the other hand, in the free-feeding
      condition, the suncus showed a relatively long fasting period in the light phase
      followed by spontaneous gastric phase III contractions. The results suggest that
      the suncus has almost the same gastrointestinal motility and motilin response as
      those found in humans and dogs, and we propose the suncus as a new small model
      animal for studying gastrointestinal motility and motilin in vivo.

PMID- 20686172
TI  - Murine vasa recta pericyte chloride conductance is controlled by calcium,
      depolarization, and kinase activity.
AB  - We used the whole cell patch-clamp technique to investigate the regulation of
      descending vasa recta (DVR) pericyte Ca(2+)-dependent Cl(-) currents (CaCC) by
      cytoplasmic Ca(2+) concentration ([Ca](CYT)), voltage, and kinase activity.
      Murine CaCC increased with voltage and electrode Ca(2+) concentration. The
      current saturated at [Ca](CYT) of ~1,000 nM and exhibited an EC(50) for Ca(2+) of
      ~500 nM, independent of depolarization potential. Activation time constants were
      between 100 and 200 ms, independent of electrode Ca(2+). Repolarization-related
      tail currents elicited by stepping from +100 mV to varying test potentials
      exhibited deactivation time constants of 50-200 ms that increased with voltage
      when electrode [Ca](CYT) was 1,000 nM. The calmodulin inhibitor N-(6-aminohexyl)
      5-chloro-1-naphthalenesulfonamide hydrochloride (W-7, 30 MUM) blocked CaCC. The
      myosin light chain kinase blockers 1-(5-iodonaphthalene-1-sulfonyl)-1H-hexahydro
      1,4-diazepine hydrochloride (ML-7, 1-50 MUM) and 1-(5-chloronaphthalene-1
      sulfonyl)-1H-hexahydro-1,4-diazepine hydrochloride (ML-9, 10 MUM) were similarly
      effective. Resting pericytes were hyperpolarized by ML-7. Pericytes exposed to
      ANG II (10 nM) depolarized from a baseline of -50 +/- 6 to -29 +/- 3 mV and were
      repolarized to -63 +/- 7 mV by exposure to 50 MUM ML-7. The Ca(2+)/calmodulin
      dependent kinase inhibitor KN-93 reduced pericyte CaCC only when it was present
      in the electrode and extracellular buffer from the time of membrane break-in. We
      conclude that murine DVR pericytes are modulated by [Ca](CYT), membrane
      potential, and phosphorylation events, suggesting that Ca(2+)-dependent Cl(-)
      conductance may be a target for regulation of vasoactivity and medullary blood
      flow in vivo.

PMID- 20686174
TI  - Dilute bird nectars: viscosity constrains food intake by licking in a sunbird.
AB  - Floral nectars of bird-pollinated plants are relatively dilute. One hypothesis
      proposed to explain this concerns the difficulty for birds of drinking nectar of
      high viscosity. We examined the effects of viscosity, separately from those of
      sugar concentration, on feeding by captive whitebellied sunbirds (Cinnyris
      talatala). Viscosities of artificial nectar (sucrose solutions ranging in
      concentration from 0.25 to 1.5 mol/l) were altered with Tylose, an inert
      polysaccharide. Food consumption was measured over 3 h, and lick frequency and
      duration were recorded using photodetection devices on feeding apertures too
      small for the bill but large enough for the extended tongue. Volumetric intake
      rates (ml/s) were inversely proportional to nectar viscosity, and were similar
      over the range of sucrose concentrations when viscosity was held constant.
      Sucrose intake rates (mg/s) remained the same on pure sucrose solutions, but they
      decreased with increasing viscosity at a constant sucrose concentration. Lick
      frequencies and tongue loads were reduced at high viscosities, and lick duration
      increased, which confirms that sunbirds take longer to ingest viscous solutions.
      Licking behavior was remarkably similar in birds feeding on different sucrose
      concentrations if viscosity was held constant. Nectar ingestion rate is
      determined by viscosity; however, total food intake is mainly modulated by sugar
      concentration. Similar effects of food viscosity have been observed in insects
      that suck nectar.

PMID- 20686173
TI  - Myocyte vascular endothelial growth factor is required for exercise-induced
      skeletal muscle angiogenesis.
AB  - We have previously shown, using a Cre-LoxP strategy, that vascular endothelial
      growth factor (VEGF) is required for the development and maintenance of skeletal
      muscle capillarity in sedentary adult mice. To determine whether VEGF expression
      is required for skeletal muscle capillary adaptation to exercise training,
      gastrocnemius muscle capillarity was measured in myocyte-specific VEGF gene
      deleted (mVEGF(-/-)) and wild-type (WT) littermate mice following 6 wk of
      treadmill running (1 h/day, 5 days/wk) at the same running speed. The effect of
      training on metabolic enzyme activity levels and whole body running performance
      was also evaluated in mVEGF(-/-) and WT mice. Posttraining capillary density was
      significantly increased by 59% (P < 0.05) in the deep muscle region of the
      gastrocnemius in WT mice but did not change in mVEGF(-/-) mice. Maximal running
      speed and time to exhaustion during submaximal running increased by 20 and 13% (P
      < 0.05), respectively, in WT mice after training but were unchanged in mVEGF(-/-)
      mice. Training led to increases in skeletal muscle citrate synthase (CS) and
      phosphofructokinase (PFK) activities in both WT and mVEGF(-/-) mice (P < 0.05),
      whereas beta-hydroxyacyl-CoA dehydrogenase (beta-HAD) activity was increased only
      in WT mice. These data demonstrate that skeletal muscle capillary adaptation to
      physical training does not occur in the absence of myocyte-expressed VEGF.
      However, skeletal muscle metabolic adaptation to exercise training takes place
      independent of myocyte VEGF expression.

PMID- 20686175
TI  - Cardiac hypertrophy, low blood pressure, and low aldosterone levels in mice
      devoid of the three circadian PAR bZip transcription factors DBP, HLF, and TEF.
AB  - The cardiovascular system is under the control of the circadian clock, and
      disturbed circadian rhythms can induce cardiovascular pathologies. This cyclic
      regulation is probably brought about by the circadian expression of genes
      encoding enzymes and regulators involved in cardiovascular functions. We have
      previously shown that the rhythmic transcription of output genes is, in part,
      regulated by the clock-controlled PAR bZip transcription factors DBP (albumin D
      site binding protein), HLF (hepatic leukemia factor), and TEF (thyrotroph
      embryonic factor). The simultaneous deletion of all three PAR bZip transcription
      factors leads to increased morbidity and shortened life span. In the present
      study, we demonstrate that Dbp/Tef/Hlf triple knockout mice develop cardiac
      hypertrophy and left ventricular dysfunction associated with a low blood
      pressure. These dysfunctions are exacerbated by an abnormal response to this low
      blood pressure characterized by low aldosterone levels. The phenotype of PAR bZip
      knockout mice highlights the importance of circadian regulators in the modulation
      of cardiovascular functions.

PMID- 20686176
TI  - PINing down the origin of prostate cancer.
AB  - The epithelium that lines the surface of prostate glands contains several cell
      types, including luminal secretory cells and basal cells of unclear function.
      Despite the fact that prostate tumors contain cells with a luminal phenotype and
      lack basal cells, a recent report indicates that the cell of origin for human
      prostate cancer is a basal cell and not a luminal cell. In contrast, another
      study indicates the reverse. It is possible that both basal and luminal
      stem/progenitor cells may independently give rise to prostate cancer; a
      comparison of the molecular signatures of the target cells of transformation with
      those of prostate tumors may aid in predicting the phenotypes of tumors with
      aggressive characteristics.

PMID- 20686177
TI  - A microbe-dependent viral key to Crohn's box.
AB  - Once Pandora unlocked her fateful box and liberated the evil forces within, it
      became impossible to put them back. Now, new work on Crohn's disease suggests the
      existence of a viral "key" that irreversibly renders a genetically susceptible
      mouse prone to pathogenesis. Indeed, dangerous liaisons among host genotype,
      viral infection, intestinal injury, and trillions of gut microbes may in part
      determine which individuals progress to a full-blown disease state. These
      findings suggest that viral and bacterial triggers may serve as therapeutic
      targets for Crohn's and prompt new hypotheses that relate inflammation, host
      immune status, microbial community structure, and human health.

PMID- 20686178
TI  - Pathway-based identification of biomarkers for targeted therapeutics:
      personalized oncology with PI3K pathway inhibitors.
AB  - Although we have made great progress in understanding the complex genetic
      alterations that underlie human cancer, it has proven difficult to identify which
      molecularly targeted therapeutics will benefit which patients. Drug-specific
      modulation of oncogenic signaling pathways in specific patient subpopulations can
      predict responsiveness to targeted therapy. Here, we report a pathway-based
      phosphoprofiling approach to identify and quantify clinically relevant, drug
      specific biomarkers for phosphatidylinositol 3-kinase (PI3K) pathway inhibitors
      that target AKT, phosphoinositide-dependent kinase 1 (PDK1), and PI3K-mammalian
      target of rapamycin (mTOR). We quantified 375 nonredundant PI3K pathway-relevant
      phosphopeptides, all containing AKT, PDK1, or mitogen-activated protein kinase
      substrate recognition motifs. Of these phosphopeptides, 71 were drug-regulated,
      11 of them by all three inhibitors. Drug-modulated phosphoproteins were enriched
      for involvement in cytoskeletal reorganization (filamin, stathmin, dynamin, PAK4,
      and PTPN14), vesicle transport (LARP1, VPS13D, and SLC20A1), and protein
      translation (S6RP and PRAS40). We then generated phosphospecific antibodies
      against selected, drug-regulated phosphorylation sites that would be suitable as
      biomarker tools for PI3K pathway inhibitors. As proof of concept, we show
      clinical translation feasibility for an antibody against phospho-PRAS40(Thr246).
      Evaluation of binding of this antibody in human cancer cell lines, a PTEN
      (phosphatase and tensin homolog deleted from chromosome 10)-deficient mouse
      prostate tumor model, and triple-negative breast tumor tissues showed that
      phospho-PRAS40(Thr246) positively correlates with PI3K pathway activation and
      predicts AKT inhibitor sensitivity. In contrast to phosphorylation of
      AKT(Thr308), the phospho-PRAS40(Thr246) epitope is highly stable in tissue
      samples and thus is ideal for immunohistochemistry. In summary, our study
      illustrates a rational approach for discovery of drug-specific biomarkers toward
      development of patient-tailored treatments.

PMID- 20686180
TI  - Beta-oxidation is essential for mouse oocyte developmental competence and early
      embryo development.
AB  - Oocyte and embryo metabolism are closely linked with their subsequent
      developmental capacity. Lipids are a potent source of cellular energy, yet little
      is known about lipid metabolism during oocyte maturation and early embryo
      development. Generation of ATP from lipids occurs within mitochondria via beta
      oxidation of fatty acids, with the rate-limiting step catalyzed by carnitine
      palmitoyl transferase I (CPT1B), a process also requiring carnitine. We sought to
      investigate the regulation and role of beta-oxidation during oocyte maturation
      and preimplantation development. Expression of Cpt1b mRNA, assessed by real-time
      RT-PCR in murine cumulus-oocyte complexes (COCs), increased following hormonal
      induction of oocyte maturation and ovulation in vivo with human chorionic
      gonadotropin (5 IU) and in embryos reaching the blastocyst stage. Beta-oxidation,
      measured by the production of (3)H(2)O from [(3)H]palmitic acid, was
      significantly increased over that in immature COCs following induction of
      maturation in vitro with epidermal growth factor (3 ng/ml) and follicle
      stimulating hormone (50 mIU/ml). The importance of lipid metabolism for oocyte
      developmental competence and early embryo development was demonstrated by
      assessing the rate of embryo development following inhibition or upregulation of
      beta-oxidation with etomoxir (an inhibitor of CPT1B) or L-carnitine,
      respectively. Inhibition of beta-oxidation during oocyte maturation or zygote
      cleavage impaired subsequent blastocyst development. In contrast, L-carnitine
      supplementation during oocyte maturation significantly increased beta-oxidation,
      improved developmental competence, and in the absence of a carbohydrate energy
      supply, significantly increased 2-cell cleavage. Thus, carnitine is an important
      cofactor for developing oocytes, and fatty acids are an important energy source
      for oocyte and embryo development.

PMID- 20686179
TI  - Ferroportin and iron regulation in breast cancer progression and prognosis.
AB  - Ferroportin and hepcidin are critical proteins for the regulation of systemic
      iron homeostasis. Ferroportin is the only known mechanism for export of
      intracellular non-heme-associated iron; its stability is regulated by the hormone
      hepcidin. Although ferroportin profoundly affects concentrations of intracellular
      iron in tissues important for systemic iron absorption and trafficking,
      ferroportin concentrations in breast cancer and their influence on growth and
      prognosis have not been examined. We demonstrate here that both ferroportin and
      hepcidin are expressed in cultured human breast epithelial cells and that
      hepcidin regulates ferroportin in these cells. Further, ferroportin protein is
      substantially reduced in breast cancer cells compared to nonmalignant breast
      epithelial cells; ferroportin protein abundance correlates with metabolically
      available iron. Ferroportin protein is also present in normal human mammary
      tissue and markedly decreased in breast cancer tissue, with the highest degree of
      anaplasia associated with lowest ferroportin expression. Transfection of breast
      cancer cells with ferroportin significantly reduces their growth after orthotopic
      implantation in the mouse mammary fat pad. Gene expression profiles in breast
      cancers from >800 women reveal that decreased ferroportin gene expression is
      associated with a significant reduction in metastasis-free and disease-specific
      survival that is independent of other breast cancer risk factors. High
      ferroportin and low hepcidin gene expression identifies an extremely favorable
      cohort of breast cancer patients who have a 10-year survival of >90%. Ferroportin
      is a pivotal protein in breast biology and a strong and independent predictor of
      prognosis in breast cancer.

PMID- 20686181
TI  - Adiponectin stimulates glucose uptake in rabbit blastocysts.
AB  - Since the discovery of adipokines, the adipose tissue is no longer considered to
      be an inactive fat storage. It secretes a variety of bioactive molecules, which
      regulate body metabolism and energy homeostasis. One of these molecules is the
      adipokine adiponectin. In different tissues, adiponectin triggers metabolic
      effects through the adenosine monophosphate-activated protein kinase (PRKA),
      which is a master regulator in glucose and lipid metabolism. Recent studies point
      to a role for adiponectin in reproduction. Adiponectin and its receptors are
      present in female reproductive tract during pregnancy, and the preimplantation
      embryo is fully equipped with adiponectin. Here, we show that both receptor
      isoforms, ADIPOR1 and ADIPOR2, are expressed in 6-day-old rabbit blastocysts. To
      investigate the signaling pathway of adiponectin in preimplantation embryos,
      rabbit blastocysts were cultured in vitro and stimulated with adiponectin.
      Supplementation of adiponectin (1 MUg/ml) enhanced PRKA alpha 1/2 (PRKAA1/2)
      phosphorylation and decreased expression of phosphoenolpyruvate carboxykinase 2
      (PCK2), a key regulator of gluconeogenesis. Inhibition of PRKAA1/2 by Compound C
      (10 MUM) restored PCK2 transcription. Adiponectin enhanced embryonic glucose
      uptake and led to a translocation of solute carrier family 2 (facilitated glucose
      transporter), member 4 (SLC2A4), previously known as GLUT4. We conclude that
      adiponectin influences the glucose metabolism of rabbit blastocysts via the
      phosphorylation of PRKAA1/2, which in turn results in a decrease of
      gluconeogenesis and an increase in glycolysis. The regulatory influence of
      adiponectin on glucose metabolism of blastocysts may be of specific interest in
      pathophysiological situations, such as obesity during pregnancy.

PMID- 20686182
TI  - Inhibition of class IIb histone deacetylase significantly improves cloning
      efficiency in mice.
AB  - Since the first mouse clone was produced by somatic cell nuclear transfer, the
      success rate of cloning in mice has been extremely low. Some histone deacetylase
      inhibitors, such as trichostatin A and scriptaid, have improved the full-term
      development of mouse clones significantly, but the mechanisms allowing for this
      are unclear. Here, we found that two other specific inhibitors, suberoylanilide
      hydroxamic acid and oxamflatin, could also reduce the rate of apoptosis in
      blastocysts, improve the full-term development of cloned mice, and increase
      establishment of nuclear transfer-generated embryonic stem cell lines
      significantly without leading to obvious abnormalities. However, another
      inhibitor, valproic acid, could not improve cloning efficiency. Suberoylanilide
      hydroxamic acid, oxamflatin, trichostatin A, and scriptaid are inhibitors for
      classes I and IIa/b histone deacetylase, whereas valproic acid is an inhibitor
      for classes I and IIa, suggesting that inhibiting class IIb histone deacetylase
      is an important step for reprogramming mouse cloning efficiency.

PMID- 20686183
TI  - Progesterone withdrawal, and not increased circulating relaxin, mediates the
      decrease in myometrial relaxin receptor (RXFP1) expression in late gestation in
      rats.
AB  - In pregnant rats, a significant decrease in myometrial relaxin family peptide
      receptor 1 (RXFP1) expression, indicative of a functional relaxin withdrawal for
      activation of myometrial contractions, occurs in late gestation and during
      spontaneous labor. This coincides with the highest level of circulating relaxin
      and a decrease in progesterone. We investigated the potential regulatory role of
      these two systemic factors on myometrial RXFP1 expression by examining the
      effects of the antiprogestin RU486 and a monoclonal antibody against rat relaxin
      (MCA1) in pregnant rats. Rats were injected with RU486 on Gestational Day (GD) 7,
      16, or 19 and were killed on GD 8, 17, or 20. RU486 caused a significant
      reduction in myometrial RXFP1. Plasma progesterone and 17beta-estradiol levels
      were increased in RU486-treated animals compared with controls. RU486 treatment
      also caused significant increases in myometrial Esr1 and Vegf and a decrease in
      Esr2. MCA1 was administered i.v. to rats from GD 17 to GD 19. On GD 20, no
      significant effect of MCA1 treatment on myometrial RXFP1 expression was observed
      compared with controls. Furthermore, there was no change in Esr1 or Esr2. A
      significant reduction in myometrial Vegf, however, was observed. We suggest that
      blocking progesterone action with RU486 increases plasma 17beta-estradiol and
      myometrial Esr1 and results in decreased RXFP1 expression. In summary, myometrial
      RXFP1 expression is mediated mainly by progesterone and not circulating relaxin
      in pregnant rats.

PMID- 20686184
TI  - Decreased expression of the rat myometrial relaxin receptor (RXFP1) in late
      pregnancy is partially mediated by the presence of the conceptus.
AB  - The actions of relaxin are mediated by relaxin family peptide receptor 1 (Rxfp1).
      In pregnant mice, myometrial Rxfp1 expression decreases at term, coinciding with
      the highest level of circulating relaxin. This down-regulation in Rxfp1 in
      reproductive tissues has not been investigated in other pregnant animals, nor are
      the regulatory mechanisms known. In the present study, we examined Rxfp1 gene and
      protein expression in the nonpregnant, pregnant, and postpartum rat uterus. The
      potential effects of local conceptus-derived factors on Rxfp1 expression were
      then examined in unilaterally pregnant rats. Immunoreactive RXFP1 was
      predominantly detected in the circular smooth muscle layer in the myometrium and
      in the decidualized endometrium. Rxfp1 was expressed in the rat myometrium from
      early to midgestation at levels similar to those in nonpregnant rat myometrium,
      with a significant reduction in expression at both the transcriptional and
      translational levels during late gestation. In unilaterally pregnant rats,
      myometrial Rxfp1 was higher in the nongravid compared to the gravid uterine horn,
      demonstrating a local negative influence of the fetal-placental unit on Rxfp1
      expression. In summary, the down-regulation in myometrial Rxfp1 expression at the
      end of gestation in the rat is partially mediated by the fetal-placental unit and
      is indicative of a functional withdrawal of relaxin. This may represent a novel
      mechanism for the activation of spontaneous uterine contractions at labor in this
      species.

PMID- 20686186
TI  - Social risk or genetic liability for psychosis? A study of children born in
      Sweden and reared by adoptive parents.
AB  - OBJECTIVE: Recent studies suggest a role for social factors during childhood in
      the later development of schizophrenia. Since social conditions in childhood are
      closely related to parental psychiatric illness, there is a need to disentangle
      how genes and social environmental factors interact. METHOD: A total of 13,163
      children born in Sweden between 1955 and 1984 and reared in Swedish adoptive
      families were linked to the National Patient Register until 2006 regarding
      admissions for non-affective psychoses, including schizophrenia. Hazard ratios
      for nonaffective psychoses were estimated in relation to three indicators of
      socioeconomic position in childhood (household data of the rearing family
      obtained via linkage to the National Censuses of 1960-1985) and in relation to
      indicator of genetic liability (biological parental inpatient care for
      psychosis). In addition, the total Swedish-born population was investigated.
      RESULTS: Increased risks for nonaffective psychosis were found among adoptees
      (without biological parental history of psychosis) reared in families with
      disadvantaged socioeconomic position, which consisted of adoptive parental
      unemployment (hazard ratio=2.0), single-parent household (hazard ratio=1.2), and
      living in apartments (hazard ratio=1.3). The risk was also increased among
      persons with genetic liability for psychosis alone (hazard ratio=4.7). Among
      those exposed to both genetic liability and a disadvantaged socioeconomic
      situation in childhood, the risk was considerably higher (hazard ratio=15.0,
      10.3, and 5.7 for parental unemployment, single-parent household, and apartment
      living, respectively). Analyses in the larger population supported these results.
      CONCLUSIONS: The results indicate that children reared in families with a
      disadvantaged socioeconomic position have an increased risk for psychosis. There
      was also some support for an interaction effect, suggesting that social
      disadvantage increases this risk more in children with genetic liability for
      psychosis.

PMID- 20686185
TI  - Family history of Alzheimer's disease and hippocampal structure in healthy
      people.
AB  - OBJECTIVE: Structural brain changes appear years before the onset of Alzheimer's
      disease, the leading cause of dementia late in life. Determining risk factors for
      such presymptomatic brain changes may assist in identifying candidates for future
      prevention treatment trials. In addition to the e4 allele of the apolipoprotein E
      gene (APOE-4), the major known genetic risk factor, a family history of
      Alzheimer's disease also increases the risk to develop the disease, reflecting
      yet unidentified genetic and, perhaps, nongenetic risks. The authors investigated
      the influence of APOE-4 genotype and family history risks on cortical thickness
      in medial temporal lobe subregions among volunteers without cognitive impairment.
      METHOD: High-resolution magnetic resonance imaging (MRI) and a cortical unfolding
      method were performed on 26 subjects (APOE-4 carriers: N=13; noncarriers: N=13)
      with at least one first-degree relative with Alzheimer's disease and 25 subjects
      (APOE-4 carriers: N=12; noncarriers: N=13) without this risk factor. All subjects
      (mean age: 62.3 years [SD=10.7]; range=38-86 years) were cognitively healthy.
      RESULTS: Family history of Alzheimer's disease and APOE-4 status were associated
      with a thinner cortex in the entorhinal region, subiculum, and adjacent medial
      temporal lobe subfields. Although these associations were additive, family
      history of Alzheimer's disease explained a greater proportion of the unique
      variance in cortical thickness than APOE-4 carrier status. CONCLUSIONS: APOE-4
      carrier status and family history of Alzheimer's disease are independently
      associated with and contribute additively to hippocampal cortical thinning.

PMID- 20686187
TI  - National trends in outpatient psychotherapy.
AB  - OBJECTIVE: The authors investigated recent trends in the use of outpatient
      psychotherapy in the United States. METHOD: Service use data from two
      representative surveys of the U.S. general population, the 1998 (N=22,953) and
      2007 (N=29,370) Medical Expenditure Panel Surveys, were analyzed, focusing on
      individuals who made more than one outpatient psychotherapy visit during that
      calendar year. The authors computed rates of any psychotherapy use; percentages
      of persons treated for mental health conditions with only psychotherapy, only
      psychotropic medication, or their combination; the mean number of psychotherapy
      visits of persons receiving psychotherapy; and psychotherapy expenditures.
      RESULTS: The percentage of persons using outpatient psychotherapy was 3.37% in
      1998 and 3.18% in 2007 (adjusted odds ratio=0.95, 95% CI=0.82-1.09). Among
      individuals receiving outpatient mental health care, use of only psychotherapy
      (15.9% and 10.5% in 1998 and 2007, respectively; adjusted odds ratio=0.66, 95%
      CI=0.48-0.90) as well as psychotherapy and psychotropic medication together
      (40.0% and 32.1%; adjusted odds ratio=0.73, 95% CI=0.59-0.90) declined while use
      of only psychotropic medication increased (44.1% and 57.4%; adjusted odds
      ratio=1.63, 95% CI=1.32-2.00). Declines occurred in annual psychotherapy visits
      per psychotherapy patient (mean values, 9.7 and 7.9; adjusted beta=-1.53,
      p<0.0001), mean expenditure per psychotherapy visit ($122.80 and $94.59;
      beta=28.21, p<0.0001), and total national psychotherapy expenditures ($10.94 and
      $7.17 billion; z=2.61, p=0.009). CONCLUSIONS: During the decade from 1998 to
      2007, the percentage of the general population who used psychotherapy remained
      stable. Over the same period, however, psychotherapy assumed a less prominent
      role in outpatient mental health care as a large and increasing proportion of
      mental health outpatients received psychotropic medication without psychotherapy.

PMID- 20686188
TI  - The genetics of autism spectrum disorders and related neuropsychiatric disorders
      in childhood.
AB  - OBJECTIVE: Autism spectrum disorders are considered to be among the most
      heritable mental disorders, a notion based on surprisingly sparse data from small
      clinical studies. Population-based studies of the heritability of other
      neuropsychiatric disorders and comorbidities among them have also been sparse.
      The authors sought to address both of these issues. METHOD: Parents of all
      Swedish 9- and 12-year-old twin pairs born between 1992 and 2000 (N=10,895) were
      interviewed regarding autism spectrum disorders and associated conditions
      (response rate, 80%). Concordance rates and structural equation modeling were
      used for evaluating causes for familial aggregation and overlap between
      conditions. RESULTS: Monozygotic twins had higher concordance rates than
      dizygotic twins for autism spectrum disorders, attention deficit hyperactivity
      disorder (ADHD), developmental coordination disorder, and tic disorder. Genetic
      effects accounted for 80% (95% CI=29-91) of the variation in liability for autism
      spectrum disorders, 79% (95% CI=61-88) for ADHD, 70% (95% CI=35-83) for
      developmental coordination disorder, and 56% (95% CI=37-68) for tic disorder.
      Among monozygotic co-twins of children with autism spectrum disorders, the
      probability of having a diagnosis of ADHD was 44%, compared with 15% for
      dizygotic co-twins. Differences in cross-disorder effects between monozygotic and
      dizygotic twins were observed for most other comorbidities, and substantial
      proportions of the genetic variance for autism spectrum disorders was shared with
      each of the other disorders. CONCLUSIONS: Different neuropsychiatric disorders
      seem to have a common genetic etiology, suggesting caution in the use of
      diagnostic entities and proband status in efforts to uncover genes predisposing
      to autism spectrum disorders.

PMID- 20686190
TI  - Resonant activation in polymer translocation: new insights into the escape
      dynamics of molecules driven by an oscillating field.
AB  - The translocation of molecules across cellular membranes or through synthetic
      nanopores is strongly affected by thermal fluctuations. In this work we study how
      the dynamics of a polymer in a noisy environment changes when the translocation
      process is driven by an oscillating electric field. An improved version of the
      Rouse model for a flexible polymer has been adopted to mimic the molecular
      dynamics, by taking into account the harmonic interactions between adjacent
      monomers and the excluded-volume effect by introducing a Lennard-Jones potential
      between all beads. A bending recoil torque has also been included in our model.
      The polymer dynamics is simulated in a two-dimensional domain by numerically
      solving the Langevin equations of motion. Thermal fluctuations are taken into
      account by introducing a Gaussian uncorrelated noise. The mean first
      translocation time of the polymer centre of inertia shows a minimum as a function
      of the frequency of the oscillating forcing field. This finding represents the
      first evidence of the resonant activation behaviour in the dynamics of polymer
      translocation.

PMID- 20686191
TI  - Surfing on a new wave of single-molecule fluorescence methods.
AB  - Single-molecule fluorescence microscopy is currently one of the most popular
      methods in the single-molecule toolbox. In this review, we discuss recent
      advances in fluorescence instrumentation and assays: these methods are
      characterized by a substantial increase in complexity of the instrumentation or
      biological samples involved. Specifically, we describe new multi-laser and multi
      colour fluorescence spectroscopy and imaging techniques, super-resolution
      microscopy imaging and the development of instruments that combine fluorescence
      detection with other single-molecule methods such as force spectroscopy. We also
      highlight two pivotal developments in basic and applied biosciences: the new
      information available from detection of single molecules in single biological
      cells and exciting developments in fluorescence-based single-molecule DNA
      sequencing.

PMID- 20686192
TI  - Nano-enhanced!

PMID- 20686194
TI  - Editorial: Etiological hypotheses of mental disorders at the molecular level.

PMID- 20686195
TI  - Glutamatergic theories of schizophrenia.
AB  - Schizophrenia is a serious mental disorder that affects up to 1% of the
      population worldwide. Traditional models of schizophrenia have emphasized
      dopaminergic dysfunction. Over the last 20 years, however, limitations of the
      dopamine model have become increasingly apparent, necessitating development of
      alternative models. Glutamatergic models are based upon the observation that the
      psychotomimetic agents such as phencyclidine (PCP) and ketamine induce psychotic
      symptoms and neurocognitive disturbances similar to those of schizophrenia by
      blocking neurotransmission at N-methyl-D-aspartate (NMDA)-type glutamate
      receptors. Because glutamate/NMDA receptors are located throughout the brain,
      glutamatergic models predict widespread cortical dysfunction with particular
      involvement of NMDA receptors throughout the brain. Further, NMDA receptors are
      located on brain circuits that regulate dopamine release, suggesting that
      dopaminergic deficits in schizophrenia may also be secondary to underlying
      glutamatergic dysfunction. Agents that stimulate NMDA receptor-mediated
      neurotransmission, including glycine-site agonists and glycine transport
      inhibitors, have shown encouraging results in preclinical studies and are
      currently undergoing clinical development. Encouraging results have been observed
      as well with agents such as metabotropic 2/3 agonists that decrease resting
      glutamate levels, reversing potential disruption in firing patterns within
      prefrontal cortex and possibly other brain regions. Overall, these findings
      suggest that glutamatergic theories may lead to new conceptualizations and
      treatment approaches that would not be possible based upon dopaminergic models
      alone.

PMID- 20686196
TI  - Regulation of intermittent oscillatory activity of pyramidal cell neurons by GABA
      inhibitory interneurons is impaired in schizophrenia: rationale for
      pharmacotherapeutic GABAergic interventions.
AB  - GABA, the major inhibitory neurotransmitter in the brain, is synthesized from L
      glutamate and packaged within a family of highly differentiated inhibitory
      interneurons. Individual GABA inhibitory interneurons in the frontal cortex can
      make terminal synaptic connections with more than 200 distinct pyramidal neurons,
      the principal output neuron. Moreover, the sites of these synaptic connections
      include shafts of dendritic spines, soma, dendritic branches, and initial axon
      segments. The phasic activity of GABAergic neurons regulate intermittent
      oscillations of assemblies of pyramidal cell neurons, which are critical for many
      higher cortical functions such as working memory. Potentially, there are several
      viable pharmacotherapeutic strategies for facilitating GABAergic
      neurotransmission. A major research question is whether tonically-administered,
      selective GABAergic therapeutic interventions can mimic and correct disruptions
      of the intermittent oscillatory activity of assemblies of cortical pyramidal cell
      neurons.

PMID- 20686197
TI  - Circadian rhythms and clock genes in psychotic disorders.
AB  - Numerous lines of evidence suggest that a disordered circadian system contributes
      to the etiology and symptomatology of major psychiatric disorders. Sleep
      disturbances, particularly rapid eye movement (REM) sleep, have been observed in
      bipolar affective disorder (BPD) and schizophrenia. Therapies aimed at altering
      the timing and duration of sleep and realigning circadian rhythms, including
      sleep scheduling, wake extension, light therapy and drug therapies that alter
      sleep and circadian rhythms appear beneficial for affective disorders.
      Interventional studies aiming to correct sleep and circadian disturbances in
      schizophrenia are scarce, although exogenous melatonin has been shown to improve
      both sleep structure and psychotic symptoms. The study of molecular clock
      mechanisms in psychiatric disorders is also gaining interest. Genetics studies
      have found associations with CLOCK, PERIOD1, PERIOD3, and TIMELESS in
      schizophrenia. Most research on BPD has focused on polymorphisms of CLOCK, but
      the lithium target GSK-3 may also be significant. New research examining the role
      of circadian rhythms and clock genes in major mental illness is likely to produce
      rapid advances in circadian-based therapeutics.

PMID- 20686198
TI  - Intrauterine factors as determinants of depressive disorder.
AB  - Although the etiology of major depressive disorder (MDD) is unknown, it is
      precipitated in susceptible individuals by adverse events. This review examines
      the role of intrauterine factors resulting from exposure to stress hormones in
      the increased vulnerability of the organism to MDD. Severe maternal stress or
      alcohol intake during the second and third trimesters causes excess release of
      corticotropin releasing hormone (CRH) and cortisol. These hormones reduce birth
      weight; impair the feedback regulation of the hypothalamic pituitary adrenal axis
      (HPA) axis and 5-HT1A and 5-HT2A signaling in key brain areas. Similar changes
      are seen in patients with MDD and in experimental animals after chronic
      inescapable stress, prenatal stress or alcohol, which also induce depressive-like
      behavior in rats, alterations in sleep and circadian rhythms reminiscent of those
      in humans with MDD. Clinical improvement of MDD by antidepressants is accompanied
      by normalization of the regulation of the HPA axis and of serotoninergic
      transmission.

PMID- 20686199
TI  - The biology of tryptophan depletion and mood disorders.
AB  - The involvement of the serotonergic system in the pathophysiology and treatment
      of affective disorders has been strongly implicated. The tryptophan depletion
      paradigm is widely used to study the effect of lowering serotonin levels.
      However, the effects observed in such studies are inconsistent and sometimes
      contradictory. The present review summarizes and discusses these discrepancies,
      emphasizing the importance of methodological details such as acute versus chronic
      tryptophan depletion, patients diagnosis and disease state: euthymic versus acute
      phase and previous drug treatment. Acute tryptophan depletion as a predictive
      test for personalized antidepressant treatment is suggested.

PMID- 20686201
TI  - Biochemical and anatomical substrates of depression and sickness behavior.
AB  - This paper reviews recent research on the contribution of the proinflammatory
      cytokine interleukin-1 (IL- 1) and the purine nucleoside adenosine in mediating
      behavioral depression and related symptoms of conservation-withdrawal in animal
      models of both major depression and illness. Activation of brain IL- 1 receptors
      appears to contribute to conservation withdrawal symptoms in animals treated with
      reserpine or lipopolysaccharide, suggesting a common underlying mechanism.
      Moreover, brain cytokine signaling is capable of recruiting adenosine signaling
      at adenosine A2A receptors, which directly mediate symptoms of behavioral
      depression. The adenosine receptors densely populate spiny GABAergic neurons in
      the striopallidal tract in the striatum and form part of an A2A/D2/mGLU receptor
      complex. Activation of these A2A receptors functionally uncouples dopamines
      excitatory motivation influence from ongoing behavior, leading to a state of
      conservation-withdrawal, and antagonism of the ventral medial striatum A2A
      receptors in reserpinated rats relieves symptoms of behavioral depression.

PMID- 20686200
TI  - Tryptophan kynurenine metabolism as a common mediator of genetic and
      environmental impacts in major depressive disorder: the serotonin hypothesis
      revisited 40 years later.
AB  - The original 1969 Lancet paper proposed in depression the activity of liver
      tryptophan-pyrrolase is stimulated by raised blood corticosteroids levels, and
      metabolism of tryptophan is shunted away from serotonin production, and towards
      kynurenine production. Discovery of neurotropic activity of kynurenines suggested
      that up-regulation of the tryptophan-kynurenine pathway not only augmented
      serotonin deficiency but also underlined depression-associated anxiety, psychosis
      and cognitive decline. The present review of genetic and hormonal factors
      regulating kynurenine pathway of tryptophan metabolism suggests that this pathway
      mediates both genetic and environmental mechanisms of depression. Rate-limiting
      enzymes of kynurenine formation, tryptophan 2,3-dioxygenase (TDO) and indoleamine
      2,3-dioxygenase (IDO) are activated by stress hormones (TDO) and/or by pro
      inflammatory cytokines (IDO). Simultaneous presence of high producers alleles of
      proinflammatory cytokines genes (e.g., interferon-gamma and tumor necrosis factor
      alpha) determines the genetic predisposition to depression via up-regulation of
      IDO while impact of environmental stresses is mediated via hormonal activation of
      TDO. Tryptophan-kynurenine pathway represents a major meeting point of gene
      environment interaction in depression and a new target for pharmacological
      intervention.

PMID- 20686202
TI  - Genetics of unipolar major depressive disorder.
AB  - Major depressive disorder (MDD) is a heterogeneous, highly prevalent, and
      moderately heritable disorder. A complex and diverse genetic-environmental
      interplay converges to set apart a significant minority that is susceptible to
      MDD, from among those who experience shorter lived and less recurrent intensive
      and incapacitating forms of sadness. The major technological advances of
      deciphering the human genome reference sequence and its common gene variations
      are beginning to allow cost effective genetic studies of unprecedented scale,
      applying increasingly denser genome wide mapping to increasingly larger case
      control samples. This effort is now at the initial stages of unraveling the
      genetic architecture of several complex phenotypes. Despite a tardy beginning,
      MDD genetic research is maturing from modest scale candidate gene association
      studies to include family-based linkage studies, and will soon allow genome wide
      case control association studies. Replicated risk conferring gene variants
      discovered so far exert a modest effect size that appears to contribute to overt
      phenotype expression in the context of a highly intricate concert of interrelated
      epigenetic and epistatic modifiers. The unraveling of additional previously
      unimplicated MDD risk conferring genes, that will throw light on molecular
      mechanisms mediating such susceptibilities, is necessary for progressing beyond
      current generation monoamine modulating antidepressant drugs. The review outlines
      basic concepts and current progress briefly overviews major replicated gene
      findings that to date mostly stem from hypotheses driven candidates, and ends
      with a discussion of current directives, including sample size and phenotype
      considerations and advancement of systematic studies of the functional
      significance of implicated gene variants, beyond their current exploratory stage.

PMID- 20686203
TI  - Commentary: Etiological hypotheses of mental disorders at the molecular level may
      not help psychiatry.

PMID- 20686204
TI  - [Development of analytical methods for residual N-methyl carbamate pesticides in
      foods].
AB  - One of the major roles of public health agencies is to ensure safe products for
      consumers through analysis of residual agricultural chemicals and veterinary
      drugs in foods. The use of agricultural chemicals and veterinary drugs in
      agriculture is necessary to improve the quality of the food produced. They play a
      beneficial role in providing a plentiful, low-cost supply of high-quality food.
      On the other hand, as a consequence of this use, the presence of residues in food
      that is a critical element of overall public health is unavoidable, and residues
      in food are of great importance in the evaluation of food quality. N-methyl
      carbamate pesticides have anticholinesterase activity and are used worldwide. The
      postcolumn HPLC method is widely used for the detection of N-methyl carbamate
      pesticides in food. However, this traditional method involves a time-consuming
      process that requires skillful techniques. Therefore we developed a new analysis
      method for N-methyl carbamate pesticides as described in detail in this paper.
      The new method, including sample preparation and determination, is simple and
      rapid and allows simultaneous determination of pesticides in food within a much
      shorter analysis time as compared with the traditional method. This should
      provide high-quality analysis and ensure safe products for consumers.

PMID- 20686205
TI  - [Development and application of practical synthetic methods of imidazolines].
AB  - This review describes the first method to prepare imidazolines from aldehydes and
      1,2-diamines by condensation and successive oxidation using NBS in one-pot
      operation. The reaction proceeds under mild conditions and can be applied to
      various aromatic and aliphatic aldehydes and 1,2-diamines. The utility of this
      method is also demonstrated in the total synthesis of spongotine A and the
      preparation of a newly designed organocatalyst, C3-symmetric trisimidazoline 7.

PMID- 20686206
TI  - [Study of the health food information for cancer patients on Japanese websites].
AB  - The aim of this paper is to evaluate the reliability of websites providing health
      food information for cancer patients and, to assess the status to get this
      information online. We used four common Japanese search engines (Yahoo!, Google,
      goo, and MSN) to look up websites on Dec. 2, 2008. The search keywords were
      "health food" and "cancer". The websites for the first 100 hits generated by each
      search engine were screened and extracted by three conditions. We extracted 64
      unique websites by the result of retrieval, of which 54 websites had information
      about health food factors. The two scales were used to evaluate the quality of
      the content on 54 websites. On the scale of reliability of information on the
      Web, the average score was 2.69+/-1.70 (maximum 6) and the median was 2.5. The
      other scale was matter need to check whether listed to use safely this
      information. On this scale, the average score was 0.72+/-1.22 (maximum 5) and the
      median was 0. Three engines showed poor correlation between the ranking and the
      latter score. But several websites on the top indicated 0 score. Fifty-four
      websites were extracted with one to four engines and the average number of search
      engines was 1.9. The two scales were positively correlated with the number of
      search engines, but these correlations were very poor. Ranking high and
      extraction by multiple search engines were of minor benefit to pick out more
      reliable information.

PMID- 20686207
TI  - [Method for the evaluation of the stability and usability after opening packages
      of orally disintegrating tablets: case of amlodipine besilate products].
AB  - Orally disintegrating (OD) tablets are widely used in clinical practice. However,
      drug information on the choice and dispensing based on their stability after
      opening packages and usability in patients and dispensaries is not sufficient.
      The aim of this study was to investigate possible evaluation methods of the
      stability and usability of amlodipine OD tablets. Additives of the brand were
      changed in April 2009, and therefore the previous and current forms and two
      generics, current and newly marketed (in November 2009) products of different
      firms, were used. OD tablets were stored at 25 degrees C and 75% relative
      humidity for 3 months after opening the packages, and their physicochemical
      properties were evaluated. Their weight, diameter, thickness, and color
      difference increased slightly from the initial state. The extent of the change in
      their hardness, disintegration time, and friability was different among products.
      These physicochemical changes were acceptable in dispensary practice. Storage
      after opening the packages did not affect their dissolution rate. The dissolution
      rate at the initial state of the current brand was slower than that of the
      previous one. All products used were able to be dispensed by an automatic tablet
      packing machine and applied to the so-called simple suspension method for
      intubational administration. Sensory evaluation tests revealed no major
      difference in the oral disintegration time, taste, impression, and preference
      among products. In conclusion, the stability and usability of amlodipine OD
      tablets used in this study were examined using several methods, and they can be
      used equivalently from the stability and usability viewpoints.

PMID- 20686208
TI  - [Tracking study to improve basic academic ability in chemistry for freshmen].
AB  - The aims of this study were to assess the basic academic ability of freshmen with
      regard to chemistry and implement suitable educational guidance measures. At
      Tohoku Pharmaceutical University, basic academic ability examinations are
      conducted in chemistry for freshmen immediately after entrance into the college.
      From 2003 to 2009, the examination was conducted using the same questions, and
      the secular changes in the mean percentage of correct response were statistically
      analyzed. An experience survey was also conducted on 2007 and 2009 freshmen
      regarding chemical experiments at senior high school. Analysis of the basic
      academic ability examinations revealed a significant decrease in the mean
      percentage of correct responses after 2007. With regard to the answers for each
      question, there was a significant decrease in the percentage of correct answers
      for approximately 80% of questions. In particular, a marked decrease was observed
      for calculation questions involving percentages. A significant decrease was also
      observed in the number of students who had experiences with chemical experiments
      in high school. However, notable results have been achieved through the
      implementation of practice incorporating calculation problems in order to improve
      calculation ability. Learning of chemistry and a lack of experimental experience
      in high school may be contributory factors in the decrease in chemistry academic
      ability. In consideration of the professional ability demanded of pharmacists,
      the decrease in calculation ability should be regarded as a serious issue and
      suitable measures for improving calculation ability are urgently required.

PMID- 20686209
TI  - Protective effect of sinomenine on cartilage degradation and chondrocytes
      apoptosis.
AB  - Sinomenine (SIN), an alkaloid extracted from the stem of the Chinese medicinal
      plant sinomenium acutum, has been used for treating rheumatoid arthritis. But
      little is known whether SIN has a protective effect on osteoarthritis (OA). In
      this study, we investigated the protective effect of SIN on IL-1beta-induced
      proteoglycan degradation and apoptosis in rabbit articular cartilage and
      chondrocytes. Treatment with 10 ng/ml IL-1beta increased the level of
      glycosaminoglycan (GAG) released into the culture media, and up-regulated the
      activity and mRNA expression of matrix metalloproteinase 13 (MMP-13) and down
      regulated the activity and mRNA expression of tissue inhibitor of
      metalloproteinase 1 (TIMP-1) in cartilage explants, as confirmed by the methods
      of GAG quantitation, MMP-13/TIMP-1 enzyme-linked immunosorbent assay (ELISA) and
      real-time quantitative RT-PCR. Treatment with 10 ng/ml IL-1beta resulted in
      marked apoptosis in chondrocytes, as demonstrated by decreased cell viability,
      occurrence of DNA laddering and increased caspase-3 activity and annexin V
      binding of phosphatidylserine. However, simultaneous treatment with SIN (10, 50
      or 250 microM) inhibited the GAG release and the activity and mRNA expression of
      MMP-13, and enhanced the activity and mRNA expression of TIMP-1 in a dose
      dependent manner in cartilage explants. Furthermore, DNA fragment, caspase-3
      activity and apoptosis rate were down-regulated, and cell viability was up
      regulated dose-dependently in chondrocytes. Thus, SIN has the protective capacity
      to antagonize cartilage degradation and chondrocyte apoptosis, which suggest that
      SIN may act as an agent for pharmacological intervention in the progress of OA.

PMID- 20686210
TI  - Simultaneous determination of ropivacaine, bupivacaine and dexamethasone in
      biodegradable PLGA microspheres by high performance liquid chromatography.
AB  - A simple and rapid high-performance liquid chromatography method coupled with UV
      detector was developed and validated for the simultaneous determination of
      ropivacaine, bupivacaine and dexamethasone in biodegradable poly(lactic-co
      glycolic acid) (PLGA) microspheres within 11 min. Chromatographic separation was
      performed on a XDB-C(18) column using a mobile phase comprised of acetonitrile
      NaH(2)PO(4) buffer (pH 3.5, 30 mM) (30:70, v/v) with a flow rate gradient
      program. The method was in good linearity (r>0.999) over the range of 0.025-40.0
      microg/ml for ropivacaine and bupivacaine, and 0.05-40 microg/ml for
      dexamethasone. The method was proved to be precise with intra- and inter-day
      precision less than 3.0% and 6.0% for all drugs and accurate with intra- and
      inter-day accuracy between -8.0% to 4.5% and between -5.0% to 5.5% for all drugs.
      The assay was rapid, simple and easy to apply. Therefore, it was very suitable
      for routine determination and quality control of ropivacaine, bupivacaine and
      dexamethasone in PLGA microspheres.

PMID- 20686211
TI  - [Development of alternative to animal experiment in evaluation of skin irritation
      caused by alcohol-based hand rubs].
AB  - Alcohol-based hand rubs are widely used for infection control in clinical
      practice. However, it is known that frequent use of the alcohol-based hand rubs
      may cause skin irritation. To predict the skin irritation in human, animal
      experiments are quite useful. Especially, the Draize Test using rabbits is
      suitable for this purpose because their skin is highly sensitive. On the other
      hand, the development of alternative to animal experiments is important not only
      from the viewpoint of ethical aspects but also from the efficient research and
      development. Reconstructed human epidermis (RhE) was developed as a human skin
      equivalent model in vitro, and has been applied to the evaluation of skin
      irritation. But the RhE has not been utilized for the evaluation of alcohol-based
      hand rubs because of the high skin permeability and cytotoxicity of alcohols. The
      aim of this study was to develop a new method using the RhE in evaluation of skin
      irritation caused by alcohol-based hand rubs. The authors propose an experimental
      technique named "Skin model blowing method (SMBM)" consisting of the sequential
      procedure as follows; applying small amount of testing sample on RhE, blow-dry,
      post incubation, and cell viability measurement. According to the SMBM, the skin
      irritation caused by alcohol-based hand rubs could be evaluated under the similar
      condition of their actual use. It was found that a high correlation existed
      between the cell viability obtained from SMBM and the skin irritation index in
      rabbit which had been reported previously.

PMID- 20686212
TI  - [Development of clinical trial education program for pharmaceutical science
      students through small group discussion and role-playing using protocol].
AB  - The acquirement of basic knowledge of clinical trials and professional attitude
      in their practices is a general instructional objective in the Model Core
      Curriculum for Pharmaceutical Education. Unfortunately, the previous program of
      clinical trial education was not effective in the acquirement of a professional
      attitude in their practices. Then, we developed the new clinical trial education
      program using protocol through small group discussion (SGD) and roll-playing. Our
      program consists of 7 steps of practical training. In step 1, the students find
      some problems after presentation of the protocol including case and prescription.
      In step 2, they analyse the extracted problems and share the information obtained
      in SGD. In steps 3 and 5, five clinical case scenarios are presented to the
      students and they discuss which case is suitable for entry to the clinical trial
      or which case corresponds to the discontinuance criteria in the present designed
      protocol. In steps 4 and 6, the roll-playing is performed by teachers and
      students as doctors and clinical research coordinators (CRC) respectively.
      Further, we conducted a trial practice based on this program for the students. In
      the student's self-evaluation into five grades, the average score of the skill
      acquisition level in each step was 3.8-4.7 grade. Our clinical trial education
      program could be effective in educating the candidates for CRC or clinical
      pharmacists.

PMID- 20686213
TI  - [Adhesion loss of syrups in a metering glass which consists of a low surface free
      energy material].
AB  - We previously reported a strong positive correlation between syrup viscosity and
      the rate of syrup loss due to adhesion to a glass metering device. In this study,
      we examined differences in the surface free energies of metering devices made of
      different polymeric materials, since reducing adhesion loss to metering devices
      could improve the efficiency of drug preparation involving highly viscous syrups.
      Among metering devices made of glass only, glass with a silicone coating (SLC),
      polypropylene (PP), and polymethylpentene (PMP) the surface free energy of the
      glass-only metering device was the highest (49.2 mN/m). The adhesion loss
      obtained for highly viscous syrups in the PP and PMP metering devices was
      significantly lower than that of the glass metering device. Measurements of syrup
      contact angles suggested that in metering devices made of PP and PMP, which have
      low surface free energies, a decrease in the spreading wetting of syrups was a
      factor in reducing the rate of adhesion loss. Thus irrespective of the syrup
      viscosity being measured, metering devices produced from materials with low
      surface free energies can reduce the time required to prepare prescriptions
      without compromising the accuracy of drug preparation.

PMID- 20686214
TI  - [Surveillance study in collaboration with a university-daycare center for elderly
      people and nursery school for children on the use of over-the-counter drugs and
      health food in Fukuyama].
AB  - To estimate the extent of use of over-the-counter (OTC) drugs and health food, we
      administered a questionnaire to the parents of children in a nursery school and
      to elderly people in a daycare center in Fukuyama city. The aim of the
      questionnaire was to determine the percentage of children and elderly people who
      use OTC drugs and health food, the purpose of using them, and the types of OTC
      drugs and health food used. Other questions concerned the person advising them on
      the use of OTC and health food, the side effects of OTC drugs and health food,
      and the awareness of children and elderly people regarding possible interactions
      between prescription drugs and OTC drugs. In children, the most frequently
      consumed OTC drugs were cold medicines (32.1%), followed by topical creams
      (22.6%) and eye lotion (14.3%). In elderly people, the most frequently consumed
      OTC products were eye lotion (18.0%), followed by laxatives (14.8%) and
      fomentation agents (13.1%). The purchase ratio of health food for children and
      elderly people were 4.8% and 11.5%, respectively. These results suggest that the
      need for OTC drugs and health food in children are very different from those in
      elderly people. In addition, in promoting self-medication, the demand for the
      opinion of a specialist occupied about 80% or 70% of the total specialist time
      among children and elderly people, respectively. Therefore, when providing
      information on health food and OTC drugs, the needs of each generation should be
      taken into account. The information obtained from the responses received will
      allow us to provide better pharmaceutical care for both children and elderly
      people in Fukuyama city.

PMID- 20686215
TI  - Impact of antimicrobial stewardship by infection control team in a Japanese
      teaching hospital.
AB  - The objective of this study is to investigate an effect on the antimicrobial
      appropriate use of the antimicrobial stewardship. We investigated the consumption
      of injectable antimicrobials from 2001 to 2007 and the administration period of
      specific antimicrobials (carbapenems, fourth-generation cephalosporins, anti
      methicillin-resistant Staphylococcus aureus (MRSA) agents) in the individual
      patient. Since September 2004, the infection control team at Osaka University
      Hospital has been promoting appropriate use of antimicrobials through
      consultation, education, and weekly surveillance of specific antimicrobial usage.
      We obtained the amount of all antimicrobial injections as titer from the medical
      information database of the electronic medical chart system retrospectively.
      Antimicrobial use densities (AUD) were evaluated by measuring the number of doses
      administered/1000 patient-days. Although the number of inpatient admissions and
      operations increased 1.53- and 1.39-fold, respectively, in the seven years from
      2001 to 2007, the expenditure on specific antimicrobials decreased markedly with
      AUD of specific antimicrobials decreasing from 39.6 to 29.2. The percentage of
      inpatients receiving specific antimicrobials decreased from 19.8% to 9.8%, and
      the ratio of the number of inpatients administered a specific antimicrobial
      within seven days to the number of inpatients administered each specific
      antimicrobial increased to over 60%. This led to reduction in the total
      expenditure of antimicrobials by about 100 million yen annually. The incidence of
      hospital-associated MRSA (HA-MRSA) infection decreased from 0.93% (2003) to 0.68%
      (2007). We can reduce the expenditure of antimicrobials without increasing
      incidence of the HA-MRSA by antimicrobial stewardship, and we think that
      appropriate use of antimicrobials is achieved progressively.

PMID- 20686216
TI  - Gemcitabine resistance induced by interaction between alternatively spliced
      segment of tenascin-C and annexin A2 in pancreatic cancer cells.
AB  - Pancreatic cancer is the fourth leading cause of cancer-related death in the
      western countries and it is resistant to almost all cytotoxic drugs. In the
      current study, we explored the gemcitabine resistance induced by the interaction
      between Annexin A2 (ANXA2) and alternatively spliced segment of tenascin-C (TNfnA
      D). In the pancreatic cancer cell culture system in vitro, it was proved that
      exogenous recombinant TNfnA-D combined with the cell surface ANXA2 specifically
      and their interaction suppressed gemcitabine-induced cytotoxicity on pancreatic
      cancer cells in a dose-dependent manner. Meanwhile, the TNfnA-D/ANXA2 interaction
      increased the phosphorylation of phosphatidylinositol 3-kinase (PI3K), Akt,
      inhibitory kappaB (IkappaB) kinase alpha/beta (IKKalpha/beta), IkappaBalpha, and
      p65 nuclear factor-kappaB (NF-kappaB) significantly. Inhibition of Akt and PI3K
      with their specific inhibitors partially reversed the suppression of gemcitabine
      induced cytotoxicity elicited by TNfnA-D/ANXA2 interaction. Activation of p65 NF
      kappaB was dependent on the phosphorylation of PI3K/Akt. The phosphorylated
      IKKalpha/beta induced the phosphorylation and degradation of IkappaBalpha, the
      sequential phosphorylation, nuclear translocation and activation of p65 NF
      kappaB. Pyrrolidine dithiocarbamate (PDTC) effectively blocked the activity of
      p65 NF-kappaB in response to TNfnA-D. Down-regulation of p65 NF-kappaB with its
      specific small interfering RNA (siRNA) restored the gemcitabine-induced
      cytotoxicity suppressed by TNfnA-D/ANXA2 interaction. For the first time, this
      study show that ANXA2/TNfnA-D interaction induced gemcitabine resistance via the
      canonical PI3K/Akt/NF-kappaB signaling pathways in pancreatic cancer cells.
      Therefore, therapy targeting ANXA2/TNfnA-D and/or p65 NF-kappaB may have
      potential clinical application for patients with pancreatic cancers.

PMID- 20686217
TI  - Isolation and characterization of chondroitin sulfates from sturgeon (Acipenser
      sinensis) and their effects on growth of fibroblasts.
AB  - Chondroitin sulfate (CS) is a glycosaminoglycan that composed of hexosamine (D
      galactosamine) and hexuronic acid (D-glucuronic acid) unit arranged in an
      alternating unbranched sequence. CS is an essential component of the
      extracellular matrix (ECM) of connective tissue. It is mainly covalently attached
      to core proteins in the form of proteoglycans so that it exhibits specific
      interactions with proteins for cell growth, differentiation, division and
      migration. In this study, CSs were purified from the cartilage and backbone of
      sturgeon (Acipenser sinensis). To characterize their biochemical properties, we
      performed disaccharide compositional analysis after chondroitinase ABC digestion,
      high performance size exclusion chromatography (HPSEC) and (1)H-NMR spectroscopy.
      We also investigated the effects of CSs on fibroblast proliferation and adhesion
      to determine whether wound healing was accelerated in vitro and proliferation of
      different mitogen-activated protein kinases (MAPK) signaling pathways was
      facilitated. The CS purified from sturgeon cartilage was primarily composed of 4
      sulfated CS (88.8%) and sturgeon backbone CS contains more than 60% 6-sulfated
      CS. The average molecular weights of CSs obtained from sturgeon cartilage and
      backbone were found to be 8 and 43 kDa, respectively. Our results showed that
      both CSs are able to increase cell adhesion, induce proliferation and migration
      on fibroblasts and may accelerate wound healing by inducing MAPK signaling
      pathways.

PMID- 20686218
TI  - Musca domestica larva lectin induces apoptosis in BEL-7402 cells through a
      mitochondria-mediated reactive oxygen species way.
AB  - A lectin from Musca domestica larva was purified by affinity chromatography on a
      glactose-Sepharose 4B column. Musca domestica larva lectin (MLL) inhibited the
      growth of BEL-7402 cells in a time and concentration-dependent way. The results
      of Hoechst 33258 staining indicated that MLL induce BEL-7402 cells apoptosis
      based on the typical apoptotic morphological changes. Subsequently, we found that
      MLL treatment abrogated glutathione antioxidant system and induced mitochondria
      to generate reactive oxygen species (ROS) accumulation, resulting in reduction of
      mitochondrial transmembrane potential. The induction of cell apoptosis was caused
      by the upregulation of Bax, the downregulation of Bcl-2, the cytochrome c release
      and the activation of the caspases pathways.

PMID- 20686219
TI  - Decursin prevents cisplatin-induced apoptosis via the enhancement of antioxidant
      enzymes in human renal epithelial cells.
AB  - Adverse effects, nephrotoxicity and hepatotoxicity, of anticancer drugs such as
      cisplatin have limited the usage for cancer therapy. Therefore, development or
      identification of supplement agents in anticancer drugs is attractive to reduce
      side effects and enhance antitumor activity. Here, we found that decursin
      isolated from Angelica gigas showed protective effects of cisplatin-induced
      damage in normal human primary renal epithelial cells (HRCs). We found that
      decursin significantly blocked cisplatin-induced cytotoxicity by 2,3-bis-(2
      methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assay in
      HRCs. Further, we found that decursin inhibited sub-G1 and cell death by
      suppression of cleavage of caspase-3, -9 and poly(ADP-ribose) polymerase (PARP)
      induced by cisplatin treatment in HRCs. Importantly, decursin effectively
      restored the activities of Cu/Zn superoxide dismutase (SOD), catalase and
      glutathione peroxidase in cisplatin-treated HRCs. Taken together, our findings
      demonstrate that decurcin prevents cisplatin-induced cytotoxicity and apoptosis
      through the activation of antioxidant enzymes in HRCs and suggest further that
      combination of decursin might suppressed adverse effects of anticancer drugs in
      cancer patients.

PMID- 20686220
TI  - The human lung cancer drug resistance-related gene BC006151 regulates
      chemosensitivity in H446/CDDP cells.
AB  - This study aimed to investigate the mechanism by which the human lung cancer drug
      resistance-related gene BC006151 regulates chemosensitivity by down-regulating
      BC006151 expression via antisense gene transfer in H446/(C)DDP cells. A
      retroviral vector containing the antisense BC006151 sequence was constructed and
      transfected into H446/(C)DDP cells. Transfection of the empty vector served as a
      negative control. The two groups of transfected cells were treated with various
      chemotherapeutic agents, after which morphological changes in cell ultrastructure
      were compared by transmission electron microscopy, cell proliferation and
      chemosensitivity to particular chemotherapeutic agents were compared by the 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method, the effects of
      chemotherapy on cell cycle and apoptosis were compared by flow cytometry, and Bcl
      2 was evaluated by immunohistochemistry and Western blot analysis. Results showed
      that apoptotic body-like structures were identified by transmission electron
      microscopy in the antisense gene-transfected cells. MTT founded that these cells
      exhibited a significantly lower level of proliferation than the control cells
      (p<0.01), together with a markedly increased sensitivity to various
      chemotherapeutic agents (p<0.01). Flow cytometry analysis revealed that a G1
      phase arrest accounted for the reduction in proliferation in the antisense gene
      transfected cells; increased apoptosis was also detected (p<0.01). Both
      immunohistochemistry and western blot analysis confirmed that Bcl-2 expression
      was significantly down-regulated in the antisense gene-transfected cells compared
      to controls. In a word, down-regulation of BC006151 can significantly inhibit
      proliferation and increase apoptosis of H446/(C)DDP cells after chemotherapy, and
      this gene may play an important role in the development of multidrug resistance
      in lung cancer.

PMID- 20686221
TI  - Apoptosis of human lung cancer cells by curcumin mediated through up-regulation
      of "growth arrest and DNA damage inducible genes 45 and 153".
AB  - The expression of "growth arrest and DNA damage inducible genes 45 and 153" is
      related to apoptotic induction of cells. GADD45 is an effector gene of the tumor
      suppressor p53, and GADD153 is associated with cellular function of cancer
      prevention. Curcumin, isolated from the plant Curcuma longa (LINN), has been
      investigated as a promising cancer preventive in food because curcumin, a
      phenolic and coloring compound, is widely ingested in the Indian subcontinent.
      However, the exact mechanisms of action of curcumin have not yet been clearly
      elucidated. Based on our successful results with green tea catechins as cancer
      preventive, we studied the relationship between the expression of GADD45 and 153
      and apoptotic induction in human lung cancer cell line PC-9. In our study
      curcumin increased the expression of GADD45 and 153 in a p53-independent manner.
      Curcumin also inhibited the growth of PC-9 cells and induced G(1)/S arrest of the
      cell-cycle followed by strong induction of apoptosis. Treatment with GADD45 and
      153 small interfering RNAs (siRNAs) inhibited the apoptotic induction in PC-9
      cells by curcumin. Moreover, curcumin induced the expression of cyclin dependent
      kinase inhibitor genes p21 and p27, while it inhibited the expression of numerous
      genes, including Bcl-2, cyclin D1, CDK2, CDK4 and CDK6. All the results with PC-9
      cells suggest that the up-regulation of GADD45 and 153 by curcumin is a prime
      mechanism in the anticancer activity of curcumin.

PMID- 20686222
TI  - Diversity and antimicrobial activity of endophytic fungi associated with the
      alpine plant Saussurea involucrata.
AB  - Endophytic fungi are rich in species diversity and may play an important role in
      the fitness of their host plants. This study investigated the diversity and
      antimicrobial potential of endophytic fungi obtained from Saussurea involucrata
      KAR. et KIR. A total of 49 endophytic fungi were isolated from S. involucrata and
      identified using morphological and molecular techniques. Extracts of fermentation
      broth from the 49 fungi were tested for antimicrobial activity against pathogenic
      microorganisms using the agar diffusion method. Forty-eight out of the 49
      endophytic fungi were identified and grouped into 14 taxa. Cylindrocarpon sp. was
      the dominant species isolated from S. involucrata, followed by Phoma sp. and
      Fusarium sp. Among the 49 endophytic fungi, 9 root isolates having darkly
      pigmented, septate hyphae were identified as dark septate endophytic (DSE)
      fungus, and 12 fungi inhibited at least one test microorganism. Moreover, 5
      strains showed a broader spectrum of antimicrobial activity and 4 strains
      displayed strong inhibition (+++) against pathogenic fungi. The results indicate
      that endophytic fungi isolated from S. involucrata are diverse in species and a
      potential source of antimicrobial agents.

PMID- 20686223
TI  - Icariin derivative inhibits inflammation through suppression of p38 mitogen
      activated protein kinase and nuclear factor-kappaB pathways.
AB  - In this study we investigated the anti-inflammatory effects of an icariin
      derivative (3,5-dihydroxy-4'-methoxy-6'',6''-dimethy1-4'',5''
      dihydropyrano[2'',3'':7,8]-flavone). We found that this icariin derivative
      inhibits tumor necrosis factor-alpha (TNF-alpha) production, inducible nitric
      oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) mRNA expression, and protein
      expression in lipopolysaccharide (LPS) stimulated RAW264.7 macrophages. It also
      alleviates paw edema induced by carrageenan in mice. To clarify the molecular
      mechanisms underlying these anti-inflammatory effects, we examined the effects of
      this compound on the phosphorylation of mitogen-activated protein kinase (MAPK),
      phosphorylation of inhibitory kappaBalpha (IkappaBalpha), and nuclear
      translocation of p65 subunit of nuclear factor (NF)-kappaB, and found it
      suppresses the activation of p38 MAPK and inhibits translocation of NF-kappaB p65
      to the nucleus through decreasing the phosphorylation of IkappaBalpha. As a
      result of these properties, this icariin derivative can be considered as a
      potential drug for inflammatory diseases.

PMID- 20686224
TI  - Inhibitory effects of cyclosporine a eye drops on symptoms in late phase and
      delayed-type reactions in allergic conjunctivitis models.
AB  - We investigated the efficacy of cyclosporine A (CyA) eye drops on ocular symptoms
      in late phase and delayed-type reactions in guinea pig allergic conjunctivitis
      models. An emulsion of ovalbumin (OVA) and Freund's complete adjuvant (FCA) was
      intraperitoneally injected into guinea pigs, and 15% OVA solution was applied
      topically to the eyes to elicit late phase reactions. Following the early phase
      reaction, increased scores for hyperemia, swelling, edema, and discharge were
      detected 6 h after antigen challenge, and CyA eye drops significantly inhibited
      the increase in scores for edema and discharge, the increase in the number of
      infiltrating inflammatory cells, and the percentage of eosinophils among
      polymorphonuclear leukocytes in conjunctival tissue. To induce delayed-type
      reactions, guinea pigs were sensitized by injecting FCA into the footpad,
      followed by injections of purified protein derivative into palpebral conjunctivae
      24 d later. Increased scores for hyperemia, swelling, and discharge were detected
      6 h after the induction of delayed-type allergy, and CyA eye drops significantly
      inhibited the increase in scores for hyperemia and swelling. In contrast,
      betamethasone sodium phosphate eye drops showed a tendency to inhibit the
      symptoms in both late phase and delayed-type reactions, or inflammatory cell
      infiltration in the late phase reaction, but the inhibition was not significant.
      These results suggest that CyA eye drops are useful for suppressing ocular
      symptoms in both late phase and delayed-type reactions in allergic conjunctivitis
      models.

PMID- 20686225
TI  - A bicarbonate-alkaline mineral water protects from ethanol-induced hemorrhagic
      gastric lesions in mice.
AB  - Ingestion of elevated amounts of ethanol in humans and rodents induces
      hemorrhagic gastric lesions, at least in part by increasing oxidative stress. The
      present study was undertaken in order to evaluate the influence of a bicarbonate
      alkaline mineral water (Uliveto on ethanol-induced hemorrhagic gastric lesions in
      mice. Lesions were evaluated by both macroscopic and microscopic analysis. In a
      first set of experiments, mice were allowed to drink Uliveto or reference water
      ad libitum until 3 h prior to intragastric (i.g.) ethanol (23 ml/kg)
      administration. Neither Uliveto nor reference water did afford any protection. In
      a second set of experiments, acute exposure to reference water (35 ml/kg, i.g.),
      given 30 min before ethanol, did not inhibit gastric lesions. However,
      administration of the same amount of Uliveto caused a remarkable reduction in
      ethanol-evoked gastric lesions. Ethanol administration increased 4-hydroxy-2
      nonenal levels, a byproduct of oxidative stress, in the luminal part of the
      gastric mucosa. This response was substantially reduced by about 70% by Uliveto,
      but not by reference water. Reference water, added with the bicarbonate content,
      present in the Uliveto water, protected against ethanol-induced lesions. Thus,
      acute pre-exposure to bicarbonate-alkaline mineral water (Uliveto) protects from
      both oxidative stress and hemorrhagic gastric lesions caused by ethanol. The
      elevated bicarbonate content of Uliveto likely accounts for the protection
      against ethanol-induced gastric injury.

PMID- 20686226
TI  - Panax notoginseng saponins attenuate atherogenesis accelerated by zymosan in
      rabbits.
AB  - Panax notoginseng saponins (PNS) are highly valued traditional Chinese medicine.
      The effects of PNS (120 mg/kg, once daily administrated intragastrically (i.g.))
      on atherosclerosis induced by a high-cholesterol diet and chronic inflammation,
      which was derived through zymosan (10 mg/kg, once every 2 d) administration
      intraperitoneally, were evaluated in rabbits for 8 weeks. A normal group, a
      simple high-fat diet group, and a zymosan plus high-cholesterol diet group (Zym)
      were used as controls. Typical pathologic changes associated with atherosclerosis
      in rabbits following induction by zymosan were alleviated by PNS treatment. After
      2, 4, 6, and 8 weeks of treatment, PNS decreased the serum levels of total
      cholesterol, triglyceride, low-density lipoprotein cholesterol, interleukin-6 and
      C-reactive protein as well as increased high-density lipoprotein cholesterol
      level significantly in comparison with those in the Zym group, except for
      triglycerides at week 2. In addition, PNS treatment significantly decreased the
      mRNA expression levels of monocyte chemoattactant protein-1 and nuclear factor
      kappaB/p65 in the aorta wall after 8 weeks of treatment compared with the Zym
      group. In conclusion, PNS attenuates atherogenesis through an antiinflammatory
      action and regulation of the blood lipid profile.

PMID- 20686227
TI  - Ameliorative potential of pralidoxime in tibial and sural nerve transection
      induced neuropathic pain in rats.
AB  - The present study was designed to investigate the ameliorative potential of
      pralidoxime in tibial and sural nerve transection-induced neuropathy in rats.
      Tibial and sural nerve transection was performed by sectioning tibial and sural
      nerve portions (2 mm) of the sciatic nerve, and leaving the common peroneal nerve
      intact. The pinprick, acetone, hot and cold tail immersion tests were performed
      to assess the degree of motor functions, mechanical hyperalgesia, cold allodynia,
      heat and cold hyperalgesia respectively. Biochemically, the tissue thio
      barbituric acid reactive species (TBARS), super-oxide anion contents (the markers
      of oxidative stress) and total calcium levels were measured. Tibial sural nerve
      transection resulted in the development of mechanical hyperalgesia, cold
      allodynia, heat and cold hyperalgesia along with the rise in oxidative stress and
      calcium levels. However, administration of pralidoxime (10, 20 mg/kg
      intraperitoneally (i.p.)) for 14 d attenuated tibial and sural nerve transection
      induced cold allodynia, mechanical, hot and cold hyperalgesia. Furthermore,
      pralidoxime also attenuated tibial and sural nerve transection induced increase
      in oxidative stress and calcium levels. It may be concluded that pralidoxime has
      ameliorative potential in attenuating the painful neuropathic state associated
      with tibial and sural nerve transection, which may possibly be attributed to
      decrease in oxidative stress and calcium levels.

PMID- 20686228
TI  - Salvianolic acid B protects SH-SY5Y neuroblastoma cells from 1-methyl-4
      phenylpyridinium-induced apoptosis.
AB  - Parkinson's disease (PD) is associated with mitochondrial dysfunction, oxidative
      stress, and activation of the apoptotic cascade. In the study, we investigated
      the effects of salvianolic acid B (Sal B) on 1-methyl-4-phenylpyridinium (MPP(+))
      treated SH-SY5Y cells, a classic in vitro model for PD. We found Sal B inhibited
      the loss of cell viability by the 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay. The underlying mechanisms of Sal B
      action were further studied. Treatment of SH-SY5Y cells with MPP(+) caused a loss
      of cell viability and mitochondrial membrane potential, condensation of nuclei,
      elevation in the level of reactive oxygen species (which was associated with
      cytochrome c release), an increase in the Bax/Bcl-2 mRNA ratio, and activation of
      caspase-3. Sal B ameliorated the MPP(+)-altered phenotypes. These results
      indicate that the Sal B protected SH-SY5Y cells against MPP(+)-induced apoptosis
      by relieving oxidative stress and modulating the apoptotic process. Our findings
      suggest that salvianolic acid B may be a promising agent to prevent PD.

PMID- 20686229
TI  - Genipin induced apoptosis associated with activation of the c-Jun NH2-terminal
      kinase and p53 protein in HeLa cells.
AB  - Genipin is a metabolite of geniposide isolated from an extract of Gardenia
      fructus. Some observations suggested that genipin could induce cell apoptosis in
      hepatoma cells and PC3 human prostate cancer cells. However, the effects of
      genipin on HeLa human cervical carcinoma cells are still unknown. In this study,
      we provided evidences that genipin induced the death of HeLa cells through
      apoptotic pathway in a dose-dependent manner. Genipin could remarkably induce
      cytotoxicity in HeLa cells and inhibit its proliferation. Induction of the
      apoptosis by genipin was confirmed by analysis of DNA fragmentation and induction
      of sub-G(1) peak through flow cytometry. The results also showed that genipin
      treated HeLa cells cycle was arrested at G(1) phase. Western blot analysis
      revealed that the phosphorylated c-Jun NH(2)-terminal kinase (JNK) protein,
      phospho-Jun protein, p53 protein and bax protein significantly increased in a
      dose-dependent manner after treatment of genipin for 24 h, and to our knowledge,
      the activation of JNK maybe result in the increase of the p53 protein level, and
      the increase of the p53 protein led to the accumulation of bax protein, bax
      protein further induced cell apoptotic death eventually. Taken all these
      together, it is possible to develop genipin as an anti-cancer drug.

PMID- 20686230
TI  - TJN-331 improves anti-glomerular basement membrane nephritis by inhibiting the
      production of intraglomerular transforming growth factor-beta1.
AB  - Transforming growth factor-beta1 (TGF-beta1) plays an important role in the
      development of glomerulonephritis. The study of experimental glomerulonephritis
      in rats was performed to examine the antinephritic effects of TJN-331, a new
      herbally-derived chemical compound. To clarify the action of TJN-331 ((E)-N-(3,4
      dimethoxyphenethyl)-N-methyl-3-(3-pyridyl)-2-propenamide) on TGF-beta1
      production, glomeruli were isolated from rats with antiglomerular basement
      membrane (GBM) nephritis and incubated for 48 h with test drugs in vitro. Next,
      we examined the effects of TJN-331 on rat anti-GBM nephritis induced by injection
      with anti-GBM serum. TJN-331 dose-dependently inhibited the increase in total and
      mature TGF-beta1 production from nephritic glomeruli, although it did not inhibit
      TGF-beta1 production from normal glomeruli. Administration of TJN-331, at a dose
      of 2 mg/kg/d, per os (p.o.), prevented proteinuria and increased crescent
      formation and adhesion of capillary walls to Bowman's capsule. The increases in
      mature TGF-beta1 protein production and TGF-beta1 staining score in nephritic
      rats were reversed by TJN-331 treatment. These results suggest that TJN-331
      inhibits proteinuria and histopathological changes in glomeruli via suppression
      of TGF-beta1 production from inflamed glomeruli.

PMID- 20686231
TI  - Novel phthalide compounds from Sparassis crispa (Hanabiratake), Hanabiratakelide
      A-C, exhibiting anti-cancer related activity.
AB  - Sparassis crispa (SC), known as Hanabiratake in Japanese, is an edible mushroom
      with various medicinal properties. We isolated 3 novel phthalides, designated
      hanabiratakelide A (1), B (2), and C (3), from the SC fruit body. In this
      investigation, 3 known phthalides (4-6), ubiquinone-9, and 2 known unsaturated
      fatty acids were also isolated. Their structures were elucidated primarily
      through extensive NMR experiments. The isolated compounds 1-6 were tested for
      their anti-oxidant activity. The in vitro superoxide dismutase-like activity of
      the 3 hanabiratakelides was stronger than that of vitamin C. The compounds also
      exerted inhibitory effects on lipopolysaccharide-stimulated nitric oxide and
      prostaglandin E2 production by a murine macrophage cell line, RAW264. In
      addition, the growth of the colon cancer cell lines Caco-2 and colon-26 was
      significantly inhibited by treatment with the 3 hanabiratakelides. In vivo, the
      frequency of azoxymethane-induced aberrant crypt foci was reduced in SC-fed
      F344/N rats compared to rats fed a standard diet. In conclusion, 3 novel
      phthalides, hanabiratakelides, derived from SC were shown to possess anti
      oxidant, anti-inflammatory, and anti-tumor activity.

PMID- 20686232
TI  - Endothelium-independent vasorelaxation by Ligusticum wallichii in isolated rat
      aorta: comparison of a butanolic fraction and tetramethylpyrazine, the main
      active component of Ligusticum wallichii.
AB  - Ligusticum wallichii is an herb widely used to treat vascular disorders in Asian
      countries, and tetramethylpyrazine (TMP) has been identified as one of its
      vasorelaxant active components. This study was performed to examine the
      endothelium-independent relaxation produced by the butanol-soluble fraction of L.
      wallichii extract (LwBt) and its possible mechanisms of action in isolated rat
      aortic rings. The effects were compared with those of TMP. LwBt produced
      vasorelaxation that increased gradually after 2-3 min of LwBt administration and
      reached a maximum within 30 min. LwBt-induced relaxation was significantly
      attenuated by pretreatment with 4-aminopyridine and apamin. Additionally, LwBt
      attenuated CaCl(2)-induced vasoconstriction in high-potassium depolarized medium.
      Thus, LwBt-induced vasorelaxation apparently involved inhibition of calcium
      influx, mediated by the opening of voltage-dependent and/or Ca(2+)-activated
      potassium channels. On the other hand, the effect of TMP was significantly
      attenuated by pretreatment with glibenclamide, and 4-aminopyridine had no effect.
      In conclusion, LwBt-induced endothelium-independent vasorelaxation was mediated
      by the opening of voltage-dependent potassium channels, while TMP-induced
      relaxation was mediated by the opening of ATP-dependent potassium channels. These
      effects of LwBt may be due to a substance other than TMP.

PMID- 20686233
TI  - Preparation and evaluation of taste-masked donepezil hydrochloride orally
      disintegrating tablets.
AB  - The purpose of this research was to prepare and evaluate a non-bitter donepezil
      hydrochloride (DH) orally disintegrating tablet (ODT) for enhanced patient
      compliance. Taste masking was done by preparing microspheres with different
      ratios of drug and Eudragit EPO using spray drying method. The entrapment of the
      drug into microspheres was confirmed by scanning electron microscope (SEM) and X
      ray powder diffraction. It was found that microspheres with a drug-polymer ratio
      of 1 : 2 could mask the taste obviously by inhibiting the release of DH in
      simulated salivary fluid. Microspheres-loaded tablets containing Polyplasdone NF
      and Low substituted Hydroxypropyl Cellulose (L-HPC) both at a 10% level showed
      rapid disintegration, in vitro (15.5 s) and in vivo (19.8 s), which were faster
      than that of marketed tablets (36.7, 41.3 s, respectively). Results from taste
      evaluation in human volunteers revealed that the ODTs with taste-masked
      microspheres had significantly enhanced palatability. Dissolution in vitro and
      pharmacokinetics in rats were evaluated for the tested ODTs compared to the
      donepezil hydrochloride commercial product (ARICEPT). Both tablets showed
      comparable dissolution patterns in vitro and similar area under curve from 0 to
      24 h (AUC(0-24)), C(max) and T(max) of DH in vivo to each other, suggesting that
      the tested ODTs might give the similar drug efficacy in rats compared to that of
      ARICEPT. Thus, it was concluded that DH ODTs with masked taste were obtained by
      Eudragit EPO-based microspheres, drug loaded microspheres neither decreased the
      bioavailability nor delayed the release of DH.

PMID- 20686234
TI  - Effect of poly(amidoamine) dendrimers on corneal penetration of puerarin.
AB  - The aim of this study was to investigate the effect of Poly(amidoamine) (PAMAM)
      dendrimers on corneal permeation of puerarin (PUE). Permeation studies were
      performed using excised cornea of rabbits by a Valia-Chien diffusion apparatus.
      Drug-treatment studies were carried out by measuring the penetration of puerarin
      on cornea in PAMAM-PUE physical mixture or PAMAM-PUE complex, and cornea
      treatment studies were carried out by measuring the penetration of puerarin on
      PAMAM dendrimer pretreated cornea in puerarin solution. The results showed that
      the permeability coefficient of puerarin in PAMAM-PUE physical mixture was
      enhanced by 2.48 (G3), 1.99 (G4) and 1.36 (G5) times on average, respectively
      compared to control. However, no significant permeability enhancement of puerarin
      in PAMAM-PUE complex was found compared to control. This may attribute to free
      drug concentration was lower in PAMAM-PUE complex which served as a depot and
      exhibited slow-released behavior of drug. Cornea-treatment studies showed that
      the lag time of puerarin was decreased, while the cumulative amount within 2.5 h
      (Q(2.5)) and the permeability coefficient of puerarin increased compared to
      control. The permeability coefficient of puerarin was linear correlated to the
      molecular weight of PAMAM dendrimer (r(2)=0.99). This indicates that higher
      generation of PAMAM dendrimer more easily interact with cornea or loosen the
      epithelium cell junctions than lower generation to increase the flux of puerarin.
      Overall, the study showed that PAMAM dendrimer increased the corneal permeation
      of puerarin mainly by altering the corneal barrier.

PMID- 20686235
TI  - Population pharmacokinetics of R- and S-carvedilol in Japanese patients with
      chronic heart failure.
AB  - Carvedilol is a beta-adrenoceptor antagonist used for treating chronic heart
      failure (CHF). Two clinical studies were conducted to evaluate the population
      pharmacokinetics and pharmacodynamics of R- and S-carvedilol, and associated
      covariates, in patients with CHF. Fifty-eight patients (male=45, female=13) with
      New York Heart Association class I-IV CHF were enrolled in two clinical studies.
      R- and S-carvedilol concentrations were measured using HPLC at steady-state after
      oral administration of carvedilol at 1.25-20 mg o.d. or b.i.d. The data from both
      studies were used to estimate the population pharmacokinetic parameters and
      covariates using the nonlinear mixed effects model program. For 40 patients
      evaluated in one clinical study, the cytochrome P450 (CYP)2D6 *1, *10, and *5
      genotypes were determined using allele-specific primer PCR, and individual
      patients' oral clearance (CL/F) of both enantiomers were estimated by the
      empirical Bayes method. A one-compartment model with a first-order absorption
      rate was established, in which body weight and alpha(1)-acid glycoprotein were
      significant covariates. Individual CL/F values for carvedilol were significantly
      lower in Japanese CHF patients with the CYP2D6 *1/*5, *5/*10 and *10/*10
      genotypes. Estimation of the population pharmacokinetic parameters and their
      covariates for each enantiomer in Japanese patients with CHF showed that the CL/F
      values for R- and S-carvedilol were dependent on body weight, alpha(1)-acid
      glycoprotein, and CYP2D6 genotype. Prediction of exposure to free plasma
      carvedilol is important for dosage adjustment of beta-blocker therapy in patients
      with CHF.

PMID- 20686236
TI  - Glycemic index and glucose utilization of rice vermicelli in healthy subjects.
AB  - Glycemic index (GI) is an indicator of glucose absorption into the systemic
      circulation after ingestion of foods. However, the plasma glucose level is
      determined by not only the absorption of glucose, but also the disappearance of
      glucose which is regulated by the insulin response. The aim of this study was to
      estimate the values of GI and glucose utilization including the absorption and
      the disappearance of glucose (U(GLU)) in the rice vermicelli (RV) using the
      resulting glucose clearance (CL(GLU)). Fifteen healthy subjects participated in
      this study. Alterations in plasma glucose and insulin levels were determined
      after ingestion of a reference food (12.5, 25, 50, 75 g glucose) and the test
      foods (white rice, long grain rice and six RV products; 50 g available
      carbohydrate). Time-course changes in plasma glucose levels were analyzed using a
      simple kinetic model. The values of CL(GLU) were calculated using the resulting
      kinetic parameters. A standard curve in which the incremental area under the
      curve of plasma insulin levels (AUC(INS(ref))) was plotted against the resulting
      CL(GLU(ref)) was generated using the reference food. The values of GI and U(GLU)
      in the RV products were calculated from the observed clearances (CL(GLU)), and
      the predicted clearances (CL(GLU(predict))) respectively, which were estimated
      using the standard curve of AUC(INS(ref)) vs. CL(GLU(ref)). It was clarified that
      the values of U(GLU) in the RV products (20-57%) were lower than those of GI (35
      62%).

PMID- 20686237
TI  - Permeation pathway of macromolecules and nanospheres through skin.
AB  - The permeation pathway of macromolecules and nanospheres through skin was
      evaluated using fluorescent isothiocyanate (FITC)-dextran (average MW, 4 kDa) (FD
      4) and nanospheres (500 nm in diameter) in hairless rat abdominal skin and
      porcine ear skin as well as a three-dimensional cultured human skin model
      (cultured skin model). A low molecular hydrophilic compound, sodium fluorescein
      (FL) (MW, 376 Da), was used for comparison. FL penetrated the stratum corneum and
      permeated the viable epidermis of hairless rat skin, whereas less permeation of
      FL was observed through the cultured skin model, suggesting that the primary
      permeation pathway for the hydrophilic material may be skin appendages through
      the rat skin. A macromolecular compound, FD-4, was distributed through the hair
      follicles of the rat skin. In addition, nanospheres were detected in the hair
      follicles of porcine skin, although no skin permeation was detected. These
      findings suggest that appendage routes such as hair follicles can be a
      penetration pathway of macromolecules and nanospheres through skin.

PMID- 20686238
TI  - Differential expression of ezrin and CLP36 in the two layers of
      syncytiotrophoblast in rats.
AB  - The syncytiotrophoblast, which regulates maternal-fetal transfer of drugs,
      consists of a single layer in humans, but two layers, i.e., SynI and SynII, in
      rodents. Polar distribution of transporters in the apical and basal plasma
      membranes of syncytiotrophoblast is important for placental function in terms of
      vectorial transport of substrates, but the mechanisms that control protein
      distribution in the syncytiotrophoblast remain unclear. We have previously
      established rat syncytiotrophoblast cell lines, TR-TBT 18d-1 and TR-TBT 18d-2,
      which retain characteristics of SynI and SynII, respectively. In this study, we
      aimed to characterize the gene expression profiles in the two layers by using
      these cell lines. DNA microarray analysis indicated that more than 25 mRNAs,
      including cytoskeleton binding proteins, ezrin and CLP36, are differentially
      expressed between TR-TBT 18d-1 and TR-TBT 18d-2. Quantitative real time
      polymerase chain reaction (PCR) analysis indicated that mRNA expression of ezrin,
      CLP36, CCN1, and CCN2 is higher in TR-TBT 18d-1 and mRNA expression of elf-1a,
      hsc70 and flot2 is higher in TR-TBT 18d-2, compared with their counterparts.
      Immunohistochemical analysis indicated that ezrin is expressed in rat placental
      villi in vivo, and is located on the apical membranes of TR-TBT 18d-1, while
      CLP36 is located in the apical and basal sides of TR-TBT 18d-1. The expression of
      ezrin was highest at gestational days 14 and 18 and was highest among the
      ezrin/radixin/moesin (ERM) family members. These results may help to clarify the
      mechanisms controlling polarization of the syncytiotrophoblast and the
      significance of the double epithelial layers in rat and mouse.

PMID- 20686239
TI  - Membrane transport mechanisms of quinidine and procainamide in renal LLC-PK1 and
      intestinal LS180 cells.
AB  - The aim of the present study was to compare the membrane transport mechanisms of
      procainamide with those of quinidine using renal epithelial LLC-PK(1) and
      intestinal epithelial LS180 cells. In LLC-PK(1) cells, the transcellular
      transport of 10 microM quinidine in the basolateral-to-apical direction was
      similar to that in the opposite direction, and 1 mM tetraethylammonium (TEA) did
      not affect the transcellular transport of the drug. On the other hand, the
      transcellular transport of 10 microM TEA and procainamide in LLC-PK(1) cells was
      directional from the basolateral side to the apical side. In addition, this
      directional transcellular transport of procainamide was diminished in the
      presence of 1 mM TEA. In LS180 cells, the temperature-dependent cellular uptake
      of 100 microM quinidine and procainamide was markedly increased by alkalization
      of the apical medium, and was inhibited significantly by 1 mM several hydrophobic
      cationic drugs, but not by TEA. The rank order of the inhibitory effects of
      hydrophobic cationic drugs on the uptake of procainamide in LS180 cells was
      imipramine>quinidine>diphenhydramine asymptotically equal
      topyrilamine>procainamide, which was consistent with that on the uptake of
      quinidine. These findings suggested that procainamide (but not quinidine) was
      transported by cation transport systems in renal epithelial cells, but that both
      procainamide and quinidine were taken up by another cation transport system in
      intestinal epithelial cells.

PMID- 20686240
TI  - Influence of pH on heat-induced aggregation and degradation of therapeutic
      monoclonal antibodies.
AB  - Monoclonal antibodies are widely used for the treatment of various diseases, and
      because therapeutic monoclonal antibodies are stored in an aqueous solution or in
      a lyophilized state, the preparation of a stabilizing formulation that prevents
      their deterioration (degradation and aggregation) is crucial. Given the
      structural similarities of the immunoglobulin G (IgG) framework regions and a
      diversity of only four subclasses, we aimed to find common conditions that
      stabilize many different antibodies. In this study, we analyzed the effect of pH
      (the most critical factor in establishing a stable formulation) on human
      monoclonal antibodies from subclasses IgG1, IgG2, and IgG4, all of which have
      been utilized in antibody therapeutics. We found that human IgGs are stable with
      minimal heat-induced degradation and aggregation at pH 5.0-5.5 irrespective of
      their subclass. We also found that IgG1 is more susceptible to fragmentation,
      whereas IgG4 is more susceptible to aggregation. This basic information
      emphasizing the influence of pH on IgG stability should facilitate the
      optimization of formulation conditions tailored to individual antibodies for
      specific uses.

PMID- 20686241
TI  - Immunoproteomic and two-dimensional difference gel electrophoresis analysis of
      Arabidopsis dehydration response element-binding protein 1A (DREB1A)-transgenic
      potato.
AB  - To produce crops that are more tolerant to stresses such as heat, cold, and salt,
      transgenic plants have been produced those express stress-associated proteins. In
      this study, we used immunoproteomic and two-dimensional difference gel
      electrophoresis (2D-DIGE) methods to investigate the allergenicity of transgenic
      potatoes expressing Arabidopsis DREB1A (dehydration responsive element-binding
      protein 1A), driven by the rd29A promoter or the 35S promoter. Immunoproteomic
      analysis using sera from potato-allergic patients revealed several immunoglobulin
      E (IgE)-binding protein spots. The patterns of protein binding were almost the
      same between transgenic and non-transgenic potatoes. The IgE-binding proteins in
      potato were identified as patatin precursors, a segment of serine protease
      inhibitor 2, and proteinase inhibitor II by matrix assisted laser
      desorption/ionization-time of flight (MALDI-TOF) MS/MS. 2D-DIGE analysis revealed
      several differences in protein expression between non-transgenic potato and
      transgenic potato; those showing increased expression in transgenic potatoes were
      identified as precursors of patatin, a major potato allergen, and those showing
      decreased expression in transgenic potatoes were identified as lipoxygenase and
      glycogen (starch) synthase. These results suggested that transgenic potatoes may
      express slightly higher levels of allergens, but their IgE-binding patterns were
      almost the same as those of control potatoes. Further research on changes in
      protein expressions in response to environmental factors is required to confirm
      whether the differences observed in this study are due to gene transfection,
      rather than environmental factors.

PMID- 20686242
TI  - High performance liquid chromatography using UV detection for the simultaneous
      quantification of the new non-nucleoside reverse transcriptase inhibitor
      etravirine (TMC-125), and 4 protease inhibitors in human plasma.
AB  - Etravirine (TMC-125, ETV) is a second-generation non-nucleoside reverse
      transcriptase inhibitor (NNRTI) that demonstrates potent activity against NNRTI
      resistant strains of human immunodeficiency virus type-1 (HIV-1). Thus, ETV has
      been used in combination with ritonavir-boosted protease inhibitor (PI) and
      integrase inhibitor for therapy-experienced HIV-1-infected patients. On the other
      hand, as ETV is a substrate and inducer of cytochrome P450 3A4 (CYP3A4), ETV may
      induce metabolism of PI and alter the concentrations of co-administered PIs. In
      order to ensure optimal drug efficacy and prevention of resistance, it is
      essential to monitor plasma concentrations of ETV and PIs. Here we describe the
      application of HPLC with UV detection for the simulataneous assay of ETV and 4
      PIs, darunavir (DRV), atazanavir (ATV), ritonavir (RTV) and lopinavir (LPV). In
      this study, the calibration curve of each drug was linear with the average
      accuracy ranging from 93.6 to 110.9%. Both intra- and interday coefficients of
      variation for each drug were less than 11.6%. The mean recovery of all drugs
      ranged from 88.0 to 97.5%. The limit of quantification was 0.04, 0.04, 0.04, 0.05
      and 0.07 microg/ml for ETV, DRV, ATV, RTV and LPV, respectively. These results
      demonstrate that our HPLC-UV method can be used for routine determination of
      plasma concentrations of ETV and 4 PIs in clinical settings.

PMID- 20686243
TI  - Purpurin as a specific inhibitor of spermidine-induced autoactivation of the
      protease plasma hyaluronan-binding protein.
AB  - Plasma hyaluronan-binding protein (PHBP), a serine protease that can activate
      coagulation factor VII and prourokinase, circulates as a single-chain form (pro
      PHBP), and is autoproteolytically converted to an active two-chain form with the
      aid of an effector such as spermidine and heparin. In this study, we screened
      natural sources for inhibitors of spermidine-induced pro-PHBP autoactivation. As
      an active agent, we purified bikaverin from a culture of a fungus. Bikaverin
      inhibited spermidine-induced autoactivation with an IC(50) of 0.45 microM, while
      it also inhibited the active form of PHBP (IC(50)=0.8 microM). Additional
      screening of related compounds led to the identification of purpurin, a plant
      anthraquinone, as a specific inhibitor: IC(50)=6.6 microM for spermidine-induced
      autoactivation; no inhibition of heparin-induced autoactivation and active PHBP.
      Alizarin and emodin, which structurally differed from purpurin in the position or
      the number of the hydroxyl groups, were less active and nonspecific. Thus, the
      position and/or the number of the hydroxyl group affect both the potency and
      selectivity of the anthraquinone inhibitors.

PMID- 20686244
TI  - Activation of the human transient receptor potential vanilloid subtype 1 by
      essential oils.
AB  - Transient receptor potential vanilloid subtype 1 (TRPV1) is a non-selective
      cation channel activated by capsaicin. TRPV1 is expressed not only on human
      sensory neurons but also on human epidermal and hair follicle keratinocytes.
      Therefore, TRPV1 could have the potential to be a therapeutic target for skin
      disorders. To search for novel TRPV1 agonists, we screened 31 essential oils by
      using human TRPV1-expressing HEK293 cells. TRPV1 was activated by 4 essential
      oils: rose, thyme geraniol, palmarosa, and tolu balsam. The dose-response curves
      for TRPV1 activation by the essential oils revealed a rank order potency [the
      half-maximal effective concentration (EC(50))] of rose>palmarosa>thyme
      geraniol>tolu balsam, and rank order efficiency (% activity in response to 1
      microM capsaicin) of tolu balsam>rose>palmarosa>thyme geraniol. Moreover, the
      dose-response curves for TRPV1 activation by citronellol (main constituent of
      rose oil) and geraniol (main constituent of thyme geraniol and palmarosa oils)
      were consistent with the potency and efficiency of each essential oil. In
      contrast, benzyl cinnamate and benzyl benzoate (main constituent of tolu balsam
      oil) and geranyl acetate (main constituent of thyme geraniol oil) did not show
      TRPV1 activity. In this first-of-its-kind study, we successfully investigated the
      role of some essential oils in promoting human TRPV1 activation, and also
      identified two monoterpenes, citronellol and geraniol, as new human TRPV1
      agonists.

PMID- 20686246
TI  - Human intestinal bacterium, strain END-2 is responsible for demethylation as well
      as lactonization during plant lignan metabolism.
AB  - A human intestinal bacterium, strain END-2, which enantioselectively oxidizes (+)
      enterodiol (END) to (+)-enterolactone (ENL) through enterolactol is also
      responsible for demethylation during plant lignan metabolism. A free hydroxyl
      group adjacent to the methoxy group is required for demethylation. The bacterium
      transformed (+)- and (-)-secoisolariciresinol to (+)-ENL and (-)-END,
      respectively, by co-incubation with strain ARC-1, which is responsible for
      dehydroxylation.

PMID- 20686245
TI  - The ethical Kampo formulation Sho-seiryu-to (TJ-19) prevents bleomycin-induced
      pulmonary fibrosis in rats.
AB  - The effects of Sho-seiryu-to (TJ-19), an ethical Kampo formulation, on bleomycin
      (BLM)-induced pulmonary fibrosis in rats was examined. Pulmonary fibrosis was
      induced by intratracheal instillation of a single dose of BLM (5 mg/kg). The TJ
      19 used consisted of at least 21 constituents, as determined by three-dimensional
      HPLC analysis, and was administered orally twice a day at a dose of 1.5 g/kg
      until the end of the study period. Changes in general appearance and body weight
      were monitored. Twenty-eight days after BLM instillation, the animals were
      sacrificed and the study parameters were measured. TJ-19 attenuated the loss in
      body weight, increase in lung/body weight ratio and concentration of
      hydroxyproline and malondialdehyde in the lung tissues induced by BLM
      administration. TJ-19 also prevented BLM-induced fibrotic changes in the lung
      histology. These protective effects of TJ-19 were observed when administration
      was started 1 week before and simultaneously with the instillation of BLM. These
      results suggest that TJ-19 has prophylactic potential against BLM-induced
      pulmonary fibrosis, and may therefore be a promising drug candidate and medicinal
      resource for preventing BLM-induced and idiopathic pulmonary fibrosis.

PMID- 20686247
TI  - Phenolic compounds from Artemisia iwayomogi and their effects on osteoblastic
      MC3T3-E1 cells.
AB  - One new (4) and twelve known phenolic compounds (1-3, 5-13) were isolated from a
      70% MeOH extract of the aerial parts of Artemisia iwayomogi. The new compound was
      identified as 7,8-dimethoxy-coumarin-9-O-(6'-O-(E)-coumaroyl)-beta-D
      glucopyranoside (4) and named iwayomin. The effects of compounds 1-13 on the
      function of osteoblastic MC3T3-E1 cells were examined by evaluating cell
      viability, alkaline phosphatase (ALP) activity, collagen synthesis, and
      mineralization in the presence of each compound. Compounds 3, 4, 7, and 9 showed
      potential in stimulating osteoblastic bone formation and may be useful for the
      prevention and/or treatment of osteoporosis.

PMID- 20686248
TI  - Feasibility of transdermal delivery of prochlorperazine.
AB  - Prochlorperazine (PCPZ) is used as a drug of first choice to treat opioid-induced
      nausea and vomiting. To examine the feasibility of the development of a
      transdermal drug delivery system for PCPZ, we performed an in vitro skin
      permeation study with hairless mouse skin. When the concentration of L-menthol in
      the hydrogel was 0-0.5%, the PCPZ flux was small; on the other hand, the flux was
      increased remarkably when the L-menthol concentration was higher than 1%. The
      optimal formulation of hydrogel would be contained 20% isopropanol (IPA), 10% N
      methyl-2-pyrrolidone (NMP), 2% L-menthol and 1% PCPZ. The strong inhibitory
      effects to stereotyped behavior were observed at 4 h after administration of PCPZ
      hydrogel, and the efficacy was sustained for at least 8 h after the
      administration in mice in vivo. Thus, it was considered that PCPZ was delivered
      to brain via systemic circulation by the administration of PCPZ hydrogel.

PMID- 20686250
TI  - Synthesis, characterization, cytotoxic activities, and DNA-binding studies of
      ternary copper(II) complexes with new coumarin derivatives.
AB  - In this study, two novel complexes [Cu(MCVH)phen(H(2)O)].ClO(4) (1) and
      [Cu(MCLH)phen(H(2)O)].ClO(4) (2) (here, MCVH(2)=(7-hydroxy-4-methyl-8-coumarinyl)
      valine, MCLH(2)=(7-hydroxy-4-methyl-8-coumarinyl) leucine) have been synthesized
      and characterized by elemental analyses, molar conductance, infrared spectra
      (IR), (1)H-NMR and UV-Vis measurements. The interactions of them with calf thymus
      DNA (ct DNA) have been investigated by absorption spectroscopy, fluorescence
      spectroscopy, circular dichroism spectroscopy and viscosity measurements.
      Experimental results reveal an intercalative interaction with DNA for the
      complexes, furthermore the binding affinity of 2 is higher than that of 1
      according to the calculated binding constant values. In addition, they were
      evaluated for their cytotoxic activities toward human prostate cancer cell (PC3),
      human liver cell (L02) and human myeloid leukemia cancer cell (HL-60) by acid
      phosphoatase assay. Both of them showed significant cytotoxic potency.

PMID- 20686251
TI  - A new method for evaluating the bitterness of medicines in development using a
      taste sensor and a disintegration testing apparatus.
AB  - The purpose of this study was to demonstrate the usefulness and wide
      applicability of a taste sensor and a new disintegration testing apparatus in the
      development and/or evaluation of orally disintegrating tablets (ODTs). In this
      paper, we described methods for the effective utilization of a taste sensor in
      the development of a new medicine. First we predicted the taste of propiverine
      hydrochloride, a model drug substance whose taste is unknown, using a taste
      sensor. Then we screened masking agents for their ability to suppress the
      bitterness of propiverine hydrochloride, and manufactured ODTs of propiverine
      hydrochloride with various masking agents. The tastes of these ODTs were then
      evaluated in chronological order by combining the taste sensor with the new
      disintegration testing apparatus, ODT-101, to resemble the oral cavity. As a
      result, we were able to evaluate the taste of propiverine hydrochloride and the
      effectiveness of various masking agents in ODTs. The result using this
      combination of taste sensor and ODT-101 shows good agreement with the results of
      human gustatory sensation testing, thus demonstrating the usefulness and
      applicability of the taste sensor and disintegration testing apparatus, ODT-101,
      in the development of new medicine.

PMID- 20686252
TI  - Preparation and the in vitro evaluation of nanoemulsion system for the
      transdermal delivery of granisetron hydrochloride.
AB  - The objective of this study was to develop and evaluate nanoemulsion system for
      transdermal delivery of granisetron hydrochloride. Pseudo-ternary phase diagram
      was constructed to ascertain the concentration range of components of
      nanoemulsion composed of isopropyl myristate (IPM) as an oil phase, tween 85 as
      surfactant, ethanol as cosurfactant, water as aqueous phase. The effects of the
      content of IPM as an oil phase and n-methyl pyrrolidone (NMP) as transdermal
      enhancer on rat skin permeation of granisetron hydrochloride nanoemulsion were
      studied in vitro. The results showed that the mean particle size of nanoemulsion
      ranged from 50.4+/-1.5 to 82.4+/-0.9 nm with homogeneous size distribution. The
      resulted optimum formulation composed of 2.5% granisetron hydrochloride, 4% IPM,
      40% tween 85/ethanol (1 : 1) and 10% NMP showed that the skin permeation rate was
      the highest (85.39+/-2.90 microg/cm(2)/h) and enhancement of drug permeability
      was 4.1-fold for transdermal delivery of granisetron hydrochloridein comparison
      with the control group (20% of tween 85 and 20% of ethanol micelle solution
      containing 2.5% of granisetron hydrochloride without IPM), and cumulative
      permeation amount was the highest (891.8+/-2.86 microg/cm(2)) with the shortest
      lag time (0.11+/-0.02 h) and was stable for at least 12 months. Therefore, the
      nanoemulsion system developed in this study offers a promising vehicle for the
      transdermal delivery system of granisetron hydrochloride, which may be as
      effective as oral or intravenous dosage forms and avoid some difficulties
      associated with these dosage forms.

PMID- 20686253
TI  - 1-(3'-[125I]Iodophenyl)-3-methy-2-pyrazolin-5-one: preparation, solution
      stability, and biodistribution in normal mice.
AB  - 3-Methyl-1-phenyl-2-pyrazolin-5-one (edaravone, 1), known as a potent free
      radical scavenger, has been developed as a medical drug for the treatment of
      acute cerebral infarction. With the aim of developing radiotracers for imaging
      free radicals in vivo, 1-(3'-[(125)I]iodophenyl)-3-methy-2-pyrazolin-5-one
      ((125)I-2) was synthesized by two methods, via isotopic exchange and interhalogen
      exchange under solvent-free conditions, in which iodo- and bromo-derivatives were
      used as labeling precursors, respectively. After HPLC purification, (125)I-2 was
      obtained in modest isolated radiochemical yields (ca. 20%) with high
      radiochemical purities by both methods. The former gave specific activities of
      0.2-0.6 kBq/micromol, whereas the latter approach achieved specific activities of
      more than 0.14 GBq/micromol. On attempting to prepare an injectable formulation
      for (125)I-2 with high specific activity, its radiochemical purities dropped to
      about 60-70%. Unlabeled analog 2 was found to have lipophilic and antioxidant
      properties similar to edaravone. Intravenous injection of (125)I-2 with low
      specific radioactivity into normal mice showed signs of distribution profiles
      similar to reported results for (14)C-labeled edaravone in normal rats.

PMID- 20686254
TI  - Crotalionosides A-C, three new megastigmane glucosides, two new pterocarpan
      glucosides and a chalcone C-glucoside from the whole plants of Crotalaria
      zanzibarica.
AB  - From a 1-BuOH-soluble fraction of the MeOH extract of the leaves of Crotalaria
      zanzibarica collected in the Okinawa Islands, three new megastigmane glucosides,
      named crotalionosides A-C, two new pterocarpan glucosides and a chalcone C
      glucoside were isolated together with two known flavonoid glycosides and one
      known megastigmane glucoside. The structures of the new compounds were elucidated
      by a combination of spectroscopic analyses. The absolute configurations of
      allenic megastigmane glucosides were determined by application of the modified
      Mosher's method. Those of the allenic moieties were determined by interpretation
      of the circular dichroism (CD) spectra of the reduction products derived from
      citrosides A and B. The aglycones of pterocarpan glucosides were found to be
      melilotocarpan B and the absolute structure of the chalcone C-glucoside was
      determined by comparison of the CD spectral behavior with the reported values.

PMID- 20686256
TI  - Development and in vitro evaluation of ibuprofen mouth dissolving tablets using
      solid dispersion technique.
AB  - The aim of present study was to prepare and evaluate mouth dissolving tablets of
      ibuprofen (IBU). Ternary solid dispersion (SD) of IBU was prepared using PEG 4000
      as carrier and Tween 80 as surfactant. The SD formulations were prepared by
      solvent evaporation and melt solvent method by varying ratio of PEG 4000.
      Different weight ratio of carrier, drug and surfactant 5 : 5 : 1, 10 : 5 : 1, 25
      : 5 : 1, 35 : 5 : 1 and 45 : 5 : 1 was taken. The prepared SD formulations were
      characterized by Fourier Transform Infra-Red (FT-IR) spectroscopy, differential
      scanning calorimetry (DSC), X-ray diffraction (XRD) and in vitro drug release.
      Mouth dissolving tablets of IBU were formulated using optimized SD formulation of
      carrier : drug : surfactant ratio, 10 : 5 : 1 along with super-disintegrants. The
      best developed formulation was compared with marketed tablet product of IBU. From
      IR and XRD studies, it may be concluded that there is change in crystalline form
      of drug into amorphous during formation of SD. From DSC studies, it was predicted
      that drug was completely dissolved in the carrier. Mouth dissolving tablets
      containing Ac-Di-Sol (12%) as super-disintegrant showed the fastest
      disintegration (202s) and in vitro drug release (84.57%). The release pattern of
      all developed formulations followed Peppas-Korsmeyer model as the plot between
      log cumulative % drug released versus log time showed good linearity (r>0.99)
      with a comparatively high slope (n) value within the range of 0.44-0.67. The
      tablets containing SD exhibited better dissolution profile than commercial
      tablets.

PMID- 20686255
TI  - Azaphilone and isocoumarin derivatives from the endophytic fungus Penicillium
      sclerotiorum PSU-A13.
AB  - Two new azaphilone derivatives, penicilazaphilones A (1) and B (2), and one new
      isocoumarin, penicilisorin (3), together with six known compounds were isolated
      from the endophytic fungus Penicillium sclerotiorum PSU-A13. Their structures
      were identified by analysis of spectroscopic data. The antimicrobial activity
      against Staphylococcus aureus, Candida albicans and Cryptococcus neoformans as
      well as the inhibitory effect on human immunodeficiency virus (HIV)-1 integrase
      and protease were examined.

PMID- 20686257
TI  - Dolabellane diterpene and three cycloartane glycosides from Thalictrum
      squarrosum.
AB  - A new dolabellane diterpene glycoside, named squoside A, and three new
      cycloartane glycosides, named squarrosides V, VI, and VII, have been isolated
      from the dried aerial parts of Thalictrum squarrosum (Ranunculaceae). Their
      structures were determined by two dimensional (2D) NMR spectroscopic analysis and
      chemical evidence.

PMID- 20686258
TI  - In vitro leishmanicidal activity of benzophenanthridine alkaloids from Bocconia
      pearcei and related compounds.
AB  - Leishmanicidal activities of benzophenanthridine alkaloids isolated from fruits
      of Bocconia pearcei and their derivatives were examined. Seven
      benzophenanthridine compounds were isolated from the methanolic extracts of B.
      pearcei. Among them, dihydrosanguinarine showed the most potent leishmanicidal
      activities (IC(50) value: 0.014 microg/ml, respectively). To examine the
      structure-activity relationship of the benzophenanthridine skeleton, the
      leishmanicidal activities for 32 synthetic samples were examined. The existence
      of bulky groups at the C(7)-C(8) position was found to enhance the activity. On
      the other hand, the bulkiness at the C(2)-C(3) position on the D-ring, a carbonyl
      group at C-6, substitution at C-6 and cleavage or saturation of the C(5)-C(6)
      bond reduced activity. A methyl group on nitrogen of the C-ring was thought to be
      necessary for significant activity.

PMID- 20686259
TI  - Evaluation of serum protein binding by using in vitro pharmacological activity
      for the effective pharmacokinetics profiling in drug discovery.
AB  - The establishment of a new index for the profile of serum protein binding was
      analyzed theoretically. The in vitro pharmacological activity ratio of the
      inhibition constant in the absence of serum protein to that in its presence
      (activity ratio), which represents the extent of specific binding to serum
      protein, was suggested as the new index. To clarify the usefulness of the
      activity ratio, theoretical analysis by the activity ratio for 3% human serum
      albumin was examined in comparison with conventional methods of equilibrium
      dialysis. In-house very late antigen-4 antagonists were used as model compounds,
      whose pharmacokinetics were strongly influenced by serum protein binding.
      Although the theoretical and actual unbound fractions were similar, the latter
      tended to be slightly lower than the former. This small difference was considered
      to correspond to nonspecific binding. These results suggested that the specific
      and nonspecific binding could be discriminated by comparing the activity ratio
      data with those of conventional methods. Moreover, the activity ratio was
      suggested to be useful in profiling the influence of protein binding on
      pharmacokinetics. In conclusion, it was considered that the activity ratio could
      avoid the risk of misleading interpretation by nonspecific binding in
      pharmacokinetics/pharmacological activity. Moreover, the activity ratio was
      considered to be valuable as one of the useful parameters in pharmacokinetics
      profiling and as a tool of rational drug design for drug discovery.

PMID- 20686260
TI  - Novel acyl-CoA: cholesterol acyltransferase inhibitor: indoline-based sulfamide
      derivatives with low lipophilicity and protein binding ratio.
AB  - To find a novel acyl-CoA: cholesterol acyltransferase inhibitor, a series of
      sulfamide derivatives were synthesized and evaluated. Compound 1d, in which
      carboxymethyl moiety at the 5-position of Pactimibe was replaced by a
      sulfamoylamino group, showed 150-fold more potent anti-foam cell formation
      activity (IC(50): 0.02 microM), 1.6-fold higher log D(7.0) (4.63), and a slightly
      lower protein binding ratio (93.2%) than Pactimibe. Compound 1i, in which the
      octyl chain at the 1-position in 1d was replaced by an ethoxyethyl, showed
      markedly low log D(7.0) (1.73) and maintained 3-fold higher anti-foam cell
      formation activity (IC(50): 1.0 microM), than Pactimibe. The plasma protein
      binding ratio (PBR) of 1i was much lower than that of Pactimibe (62.5% vs.
      98.1%), and its partition ratio to the rabbit atherosclerotic aorta after oral
      administration was higher than that of Pactimibe. Compound 1i at 10 microM
      markedly inhibited cholesterol esterification in atherosclerotic rabbit aortas
      even when incubated with serum, while Pactimibe had little effect probably due to
      its high PBR. In conclusion, compound 1i is expected to more efficiently inhibit
      the progression of atherosclerosis than Pactimibe.

PMID- 20686261
TI  - Novel tetrahydroisoquinoline derivatives with inhibitory activities against acyl
      CoA: cholesterol acyltransferase and lipid peroxidation.
AB  - To find a novel acyl-CoA: cholesterol acyltransferase (ACAT) inhibitor with anti
      lipid peroxidative activity, a series of tetrahydroisoquinoline derivatives were
      synthesized and evaluated. A compound with a N-(4-hydroxy-2,3,5
      trimethylphenyl)carbamoyl moiety at the 3-position and an octanoyl moiety at the
      2-position (7) was demonstrated to show anti-foam cell formation activity
      stronger than and anti-lipid peroxidative activity comparable to those of
      Pactimibe, while it was hardly absorbed orally. To increase its bioavailability,
      the acyl chain at the 2-position was shortened and various polar or basic
      moieties were introduced at the 7-position of 7. Among the synthesized
      derivatives, (S)-7-dimethylamino-N-(4-hydroxy-2,3,5-trimethylphenyl)-2-isobutyryl
      1,2,3,4-tetrahydroisoquinoline-3-carboxamide hydrochloride (21) showed about 16
      fold stronger anti-foam cell formation activity, 3-fold stronger hepatic ACAT
      inhibitory activity, similar anti-low density lipoprotein (LDL) oxidative
      activity and 2-fold more potent protective activity against macrophage cell death
      by oxidative stress in comparison with Pactimibe. Compound 21 was efficiently
      absorbed after oral administration at 10 mg/kg in rats and dogs and its C(max)
      values were higher than its IC(50) values for in vitro activities. In conclusion,
      a tetrahydroisoquinoline structure is a useful scaffold for designing a phenolic
      anti-oxidative ACAT inhibitor, and compound 21 is expected to effectively prevent
      atherosclerosis.

PMID- 20686262
TI  - Synthesis, crystal structure, antioxidant activity, and DNA-binding studies of a
      novel Ni(II) [2x2] grid complex with a rigid bistridentate Schiff base ligand.
AB  - With a bistridentate Schiff-base ligand, N',N'(3)-bis[(1E)-1-(2
      pyridinyl)ethylidene)] isophthalohydrazide (H(2)L), a [2x2]G grid complex,
      [Ni(4)(HL)(4)](ClO(4))(4).4H(2)O.0.5 CH(3)OH (1) has been synthesized and
      characterized spectroscopically and crystallographically. Spectrometric
      titrations, ethidium bromide displacement experiments, circular dichroism
      spectral analysis and viscosity measurements indicate that the compound 1
      strongly binds with calf-thymus DNA, presumably via intercalation mechanism.
      Furthermore, the antioxidant activity (superoxide and hydroxyl radical) of the
      ligand and its nickel(II) complex is determined by using spectrophotometer
      methods in vitro. Complex 1 is found to possess potent antioxidant activity and
      be better than standard antioxidants like mannitol.

PMID- 20686263
TI  - Synthesis and antibacterial activity of some novel 6-(1H-benz[d]imidazol-2-yl)-8
      (5-nitro-2-furyl)-3-(4-pyridyl)-7,8-dihydro[1,2,4]triazolo[3,4
      b][1,3,4]thiadiazepines.
AB  - A new series of novel 6-(1H-benz[d]imidazol-2-yl)-8-(5-nitro-2-furyl)-3-(4
      pyridyl)-7,8-dihydro[1,2,4]triazolo[3,4-b][1,3,4]thiadiazepines 8a-d has been
      synthesized. These compounds were evaluated for their efficiency as antibacterial
      agents against two Gram-positive and Gram-negative strains of bacteria along with
      antifungal activity against two fungal organisms. The antibacterial and
      antifungal activities of the present compounds were not comparable with those of
      the standard drugs employed. But, however, all the test compounds could exhibit
      notable activities only at higher concentrations (250, 500 microg/ml). The
      chemical structures of these compounds were confirmed on the basis of spectral
      data.

PMID- 20686264
TI  - Oppositinines A and B: new vasorelaxant beta-carboline alkaloids from Neisosperma
      oppositifolia.
AB  - A phytochemical study on the bark of Neisosperma oppositifolia (Apocynaceae)
      yielded two new beta-carboline indole alkaloids, oppositinines A (1) and B (2),
      together with five known alkaloids, isoreserpiline, isocarapanaubine, vobasine,
      10-methoxydihydrocorynantheol-N-oxide, and ochropposinine oxindole. Structural
      elucidation of 1 and 2 was performed using 2D NMR methods. Oppositinines A (1)
      and B (2) showed potent vasorelaxant effects on the rat aorta.

PMID- 20686265
TI  - Three new cardenolides from methanol extract of stems and twigs of Nerium
      oleander.
AB  - Two new cardenolide monoglycosides, cardenolides B-1 (1) and B-2 (2) were
      isolated from Nerium oleander, together with oleagenin (3) which is the first
      isolated compound from natural sources. The structure of compounds 1-3 were
      established on the basis of their spectroscopic data.

PMID- 20686266
TI  - Two new aristolochic acid derivatives from the roots of Aristolochia fangchi and
      their cytotoxicities.
AB  - Phytochemical investigation of 90% ethanol extracts of the roots of Aristolochia
      fangchi yielded two new aristolochic acid derivatives named Aristolochic Acid F
      and Aristolochic Acid G, together with three known compounds. Their structures
      were elucidated by spectral analysis. The cytotoxicity of the isolated compounds
      was also determined.

PMID- 20686267
TI  - Effect of particle size on skin permeation and retention of piroxicam in aqueous
      suspension.
AB  - The effects of particle size on the skin permeation and retention of piroxicam
      (PXC) in an aqueous suspension were investigated. PXC particles of about 23 nm,
      173 nm, and 2.1 microm in size were prepared by the cogrinding of
      PXC/polyvinylpyrrolidone (PVP) K12/sodium dodecyl sulfate physical mixture (mean
      particle size, 9.6 microm) using a vibrational rod and ball mills. Particles were
      stable after storage in 0.1 m acetate buffer (pH 4.5) for 24 h. The amount of PXC
      that permeated and was retained in hairless mouse skin increased with the
      reduction of particle size up to 23 nm. Amorphous PXC was formed when PXC was
      coground with PVP, though the amorphous formation did not affect the amount of
      PXC permeated. Reduction of particle size to less than 50 nm, and the subsequent
      increase in surface area of PXC nanocrystals appeared to affect skin permeation
      and retention behavior.

PMID- 20686268
TI  - Triterpenoid derivatives from Cylicodiscus gabunensis.
AB  - Three new olean-12-ene derivatives (1-3), together with known urs-12-ene-3beta,
      28-diol (4) were isolated from the stem root of Cylicodiscus gabunensis. The
      structures of the new compounds were established by chemical and spectroscopic
      means as beta-amyrin-n-nonyl ether (1), 22alpha-hydroxyolean-12-en-3beta-yl-beta
      D-galactopyranoside (2), and 24-hydroxyolean-12-en-3beta-yl-beta-D
      glucopyranoside (3).

PMID- 20686269
TI  - Chemical synthesis of (22E)-3alpha,6alpha,7alpha,12alpha-Tetrahydroxy-5beta-chol
      22-en-24-oic acid and its N-acylamidated conjugates with glycine or taurine:
      precursors of the [22,23-(3)H] labelled tracers.
AB  - (22E)-3alpha,6alpha,7alpha,12alpha-Tetrahydroxy-5beta-chol-22-en-24-oic acid and
      its N-acylamidated conjugates with glycine or taurine were synthesized from
      cholic acid. The key reactions employed are: 1) degradation of the side chain in
      intermediary C(24) 3alpha,6alpha,7alpha,12alpha-tetrahydroxylated bile acid to
      the corresponding C(22) 23,24-dinor-aldehyde, followed by Wittig reaction with
      methyl (triphenylphosphoranylidene)acetate and 2) N-acylamidation of the
      unconjugated tetrahydroxy-Delta(22)-5beta-cholenoic acid with glycine (or
      taurine) in the presence of diethylphosphorocyanide and triethylamine as coupling
      reagents.

PMID- 20686270
TI  - An effective synthesis of 5,4'-disubstituted flavones via a cesium enolate
      assisted intramolecular ipso-substitution reaction.
AB  - A variety of 5,4'-disubstituted flavones, which are anticipated to be androgen
      receptor antagonists to treat diseases mediated by the androgen receptor, were
      synthesized. It was found that an intramolecular ipso-substitution reaction via
      cesium enolate using 2-fluoro-6-hydroxyacetophenone and various benzoyl chlorides
      was effective in the preparation of 5-hydroxy-4'-alkylflavones.

PMID- 20686271
TI  - Steamed ginseng-leaf components enhance cytotoxic effects on human leukemia HL-60
      cells.
AB  - Three new dammarane-type glycosides, named ginsenosides SL(1)-SL(3) (1-3), and
      eleven known compounds (4-14) were isolated from the heat-processed leaves of
      Panax ginseng. Their structures were elucidated on the basis of extensive
      chemical and spectroscopic methods. Cytotoxic-activity testing of compounds 1-14
      against human leukemia HL-60 cells showed that ginsenosides Rh(3) (11) and Rk(2)
      (12) exhibited potent effects with IC(50) values of 0.8 and 0.9 microM. In
      addition, ginsenosides SL(3) (3), 20S-Rg(2) (7), F(4) (10), 20S-Rh(2) (13)
      displayed strong activity with IC(50) values of 9.0, 9.0, 7.5, and 8.2 microM,
      respectively. This is the first report on chemical components of the steamed
      ginseng leaves.

PMID- 20686272
TI  - Cucullamide, a new putrescine bisamide from Amoora cucullata.
AB  - A new putrescine bisamide derivative named cucullamide (1) was isolated from the
      leaves of Amoora cucullata, together with five known natural products,
      dasyclamide (2), ent-2beta-hydroxymanool (3), chrysin (4), apigenin (5), and
      kaempferol-3-O-beta-D-glucopyranoside (6). The structure of the new isolated
      compound was elucidated on the basis of 1D and 2D NMR as well as high resolution
      electrospray ionization (HR-ESI)-MS spectroscopic analysis.

PMID- 20686273
TI  - Structures of new Erythrinan alkaloids and nitric oxide production inhibitors
      from Erythrina crista-galli.
AB  - Two new Erythrinan alkaloids, cristanines A and B (1, 2), were isolated from the
      bark of Erythrina crista-galli L. together with nine known Erythrinan alkaloids
      (3-5, 7-12) and an indole alkaloid (13). The structures of the compounds,
      cristanines A (1) and B (2), were elucidated by spectroscopic methods. Three of
      the twelve compounds isolated showed significant inhibitory activity on
      lipopolysaccharide induced nitric oxide (NO) production.

PMID- 20686274
TI  - Antibacterial activity of 5-dialkylaminomethylhydantoins and related compounds.
AB  - To find new antibacterial leads in the class of hydantoin derivatives, we carried
      out synthetic investigation and biological evaluation of the title hydantoin
      derivatives and related compounds. Among the hydantoin derivatives described in
      this article, compound 3o, in which a 2,6-dichlorophenyl ring was introduced at
      the N-3 position of the hydantoin nucleus, showed the highest levels of
      antibacterial activity against both Escherichia coli NBRC14237 (NIHJ) and
      Staphylococcus aureus ATCC6538P (gram-negative and gram-positive bacteria,
      respectively) strains.

PMID- 20686275
TI  - Age-associated adaptations in murine adipose tissues.
AB  - Ageing is associated with an increase in visceral obesity in men and women.
      Although wild-type mice with a C57Bl/6 genetic background are extensively used in
      studies on obesity and metabolism, little information is available on age
      associated changes in their adipose tissues. We have evaluated development and
      composition of subcutaneous (SC) and gonadal (GON) adipose tissue in male C57Bl/6
      mice at the ages of 10 weeks, 12 months or 24 months, while kept on normal chow.
      Total body weight as well as SC and GON fat mass significantly increased between
      10 weeks and 12 months, but markedly decreased again up to 24 months of age.
      Adipocyte size in both fat depots and blood vessel size in GON fat followed this
      trend. Plasma leptin levels correlated positively with body weight and SC or GON
      fat mass. Both 12 and 24 months old mice displayed better insulin sensitivity as
      compared to 10 weeks old counterparts, reflected by significantly decreased
      plasma levels of insulin and/or glucose. Thus, ageing of C57Bl/6 male mice is
      associated with a biphasic pattern (increase up to 12 months followed by a
      decrease up to 24 months) of body weight, SC and GON fat mass, adipocyte and
      blood vessel size.

PMID- 20686276
TI  - Efficacy of the addition of prokinetics for proton pump inhibitor (PPI) resistant
      non-erosive reflux disease (NERD) patients: significance of frequency scale for
      the symptom of GERD (FSSG) on decision of treatment strategy.
AB  - BACKGROUND: Non-erosive reflux disease (NERD) is a more difficult to treat than
      reflux esophagitis (RE) due to the high prevalence of PPI resistance.
      Consequently, the treatment strategy for NERD is yet to be established. PATIENTS
      AND METHODS: Subjects were 467 GERD patients (NERD 349, RE 118, 47.4 +/- 16.7
      years) with reflux symptoms such as heartburn. PPI was administered for 2 weeks,
      and total score (TS) of symptoms, seven items of reflux symptoms e.g. heartburn
      (reflux score: RS), and five items of dyspeptic symptoms e.g. heavy stomach
      (dyspeptic score: DS) were assessed using the frequency scale for the symptoms of
      GERD (FSSG), a GERD-specific questionnaire developed in Japan. Improvement <50%
      in TS was defined as non-responder. Patients' background, and pretreatment TS,
      RS, DS, and 12 items of FSSG were assessed. Furthermore, the effect of additional
      prokinetics (4 weeks) for 117 PPI non-response NERD patients was also examined.
      RESULTS: Younger age, constipation, higher TS, DS, F2 (bloated stomach), 3 (heavy
      stomach), 5 (sick feeling after meal), 8 (satiety during meal) in FSSG were
      factors to be PPI non-responders in NERD. Significant improvement in TS were
      observed (pretreatment: 17.4 +/- 7.7 vs. 2 weeks 14.6 +/- 6.0 vs. 6 weeks 7.7 +/-
      5.2, p<0.0001) after the addition of prokinetics in PPI non-response NERD.
      CONCLUSION: Younger age, constipation, dysmotility were factors of PPI non
      response in NERD. As high DS is correlated with PPI non-response, it is indicated
      that patients with strong dysmotility and functional dyspepsia complication might
      be PPI resistant. The efficacy of additional prokinetics for PPI non-response
      NERD was observed.

PMID- 20686277
TI  - Comparison among body mass index (BMI), waist circumference (WC), and percent
      body fat (%BF) as anthropometric markers for the clustering of metabolic risk
      factors in Japanese.
AB  - OBJECTIVE: To compare body mass index (BMI), waist circumference (WC), and
      percent body fat (%BF) as markers for the clustering of metabolic risk factors in
      Japanese. METHODS: Age-adjusted correlation coefficients (Rs) were calculated
      between the three anthropometric markers of obesity and metabolic risk factors in
      2,444 men and 1,442 women among Japanese. Areas under receiver operating
      characteristic curves (AUCs) of BMI, WC, and %BF were calculated for diagnosing
      the clustering of 1 or more, 2 or more, 3 or more, and 4 risk factors among
      increased blood pressure, impaired fasting glucose, increased triglycerides, and
      decreased HDL cholesterol and for the clustering of 1 or more, 2 or more, 3 or
      more, 4 or more, 5 or more, and 6 risk factors among the upper four risk factors
      as well as increased high-sensitivity C-reactive protein and increased LDL
      cholesterol. RESULTS: The Rs were not significantly different among BMI, WC, and
      %BF except for the difference between the R of BMI (0.217) and that of %BF
      (0.283) with LDL cholesterol in men (p=0.014). The AUCs of BMI, WC, and %BF for
      diagnosing any of the risk factor clustering patterns defined above were not
      significantly different in both men and women. CONCLUSION: The AUCs for
      diagnosing the clustering of metabolic risk factors were not significantly
      different among BMI, WC, and %BF.

PMID- 20686278
TI  - Clustering of cardiovascular risk factors and blood pressure control status in
      hypertensive patients.
AB  - OBJECTIVE: Hypertensive patients have multiple risk factors such as chronic
      kidney disease (CKD) and hyperuricemia in addition to components of metabolic
      syndrome. The morbidity of cardiovascular diseases is expected to increase
      synergistically by clustering of them. In the present study, we assessed the
      clustering of cardiovascular risk factors and blood pressure (BP) control status
      in hypertensive patients. METHODS AND PATIENTS: Subjects were 699 treated
      hypertensive patients (mean age: 65 +/- 12 years; males 297, females 402) who had
      been followed at National Kyushu Medical Center, Fukuoka, Japan. We assessed the
      status of BP control and the presence of comorbidity including obesity, diabetes
      mellitus (DM), dyslipidemia, CKD and hyperuricemia. RESULTS: Average BP level and
      the number of antihypertensive drugs were 133 +/- 11/74 +/- 10 mmHg and 2.0 +/-
      1.1, respectively and the average number of cardiovascular risk factors was 1.5
      +/- 1.1. No comorbid risk factors were found in 18.7% of the patients. On the
      other hand, 34.2%, 28.9% and 18.2% of the patients had one, two or more than
      three risk factors, respectively. There were no significant differences in BP
      among these groups, while patients with three or more risk factors needed a
      greater number of antihypertensive drugs than those with other groups. Patients
      with three or more risk factors group showed significantly higher body mass
      index, serum LDL cholesterol, triglyceride, plasma glucose and serum uric acid
      levels compared to those with other groups (p<0.05, respectively). They also
      showed significantly lower serum HDL cholesterol and estimated GFR levels
      compared to those in other groups (p<0.05, respectively). CONCLUSION: These
      results suggest that the majority of the treated hypertensive patients are
      complicated with additional cardiovascular risk factors and the patients with
      clustering risk factors required a greater number of antihypertensive drugs.
      Integrative management of BP as well as comorbid risk factors should be
      encouraged.

PMID- 20686279
TI  - Relationship between habit of cigarette smoking and airflow limitation in healthy
      Japanese individuals: the Takahata study.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by
      chronic airflow limitation. The prevalence of airflow limitation in Japan is
      10.9% (16.4% of males and 5.0% of females). Cigarette smoking is well known as a
      major cause of COPD. However, few epidemiological studies have evaluated the
      effects of cigarette smoking on pulmonary function in healthy subjects. METHODS:
      Subjects aged 40 years or older (n=2,917), who had participated in a community
      based annual health check in Takahata, Japan, from 2004 through 2005, were
      enrolled in the study. The smoking histories of these subjects were investigated
      using a self-reported questionnaire. Forced vital capacity (FVC), forced
      expiratory volume in 1 second (FEV(1)), and forced expiratory flow at 25-75% of
      FVC (FEF(25-75)) were measured by standard procedures using spirometric machines.
      RESULTS: There were 554 current smokers (18.6%) and 403 former smokers (13.8%).
      The prevalence of airflow limitation defined by FEV(1)/FVC <0.7 in this
      population was 10.6%, and prevalence of airflow limitation defined by 5th
      percentile lower limit of normal was 6.4%. In smokers, percent predicted values
      of measured spirometric parameters (%FVC, %FEV(1) and %FEF(25-75)) decreased
      significantly with age, except for male %FVC. Also, percent predicted values of
      measured spirometric parameters decreased significantly with increasing pack
      years, except for female %FEF(25-75). CONCLUSION: Cigarette smoking increased the
      prevalence and severity of airflow limitation. It is concluded that cigarette
      smoking increases the risk of airflow limitation in a healthy Japanese
      population.

PMID- 20686280
TI  - Noninvasive ventilation improves the outcome of pulmonary complications after
      liver resection.
AB  - BACKGROUND: Pulmonary complications are associated with increased mortality after
      liver resection. Although noninvasive ventilation (NIV) has proved to be an
      effective treatment for respiratory failure after abdominal surgery, including
      organ transplantation, its efficacy for pulmonary complications following liver
      resection per se has not been reported. The aim of this retrospective study was
      to investigate the effects of NIV in patients with postoperative pulmonary
      complications after liver resection. METHODS: A retrospective single center
      study. Between April 2002 and March 2005, we used NIV in 16 patients who met the
      criteria for NIV after liver resection: respiratory failure and/or a massive
      atelectasis (NIV group). We also reviewed data on 10 patients who underwent liver
      resection from April 1999 to March 2002, and met the criteria for NIV after the
      operation and received conventional treatment (non-NIV group). RESULTS:
      Respiratory-cause mortality was significantly lower in NIV group than in non-NIV
      group (0.0% vs. 40.0%, p=0.007), and all-cause mortality tended to be lower in
      NIV group (18.8% vs. 50.0%, p=0.100). After NIV treatment for 24 hours, the
      PaO(2)/FiO(2) ratio and PaCO(2) were improved significantly but no significant
      improvement was noted in non-NIV group. Rate of reintubation was significantly
      lower in NIV group (12.5% vs. 50.0%, p=0.040). NIV was tolerated in all 16 NIV
      group patients, and no severe NIV-related complications were observed.
      CONCLUSION: NIV is effective in patients with respiratory failure and/or massive
      atelectasis after liver resection.

PMID- 20686281
TI  - Noninvasive ventilation in acute exacerbation of idiopathic pulmonary fibrosis.
AB  - BACKGROUND AND OBJECTIVE: The outcome of acute exacerbation of idiopathic
      pulmonary fibrosis (AE-IPF) is usually very poor, and it has been suggested that
      mechanical ventilation does not benefit AE-IPF patients. Noninvasive ventilation
      (NIV) has attracted attention as a means to avoid intubation in acute respiratory
      failure, including acute respiratory distress syndrome (ARDS). This study
      describes the outcome of patients with AE-IPF who were treated with NIV. METHODS:
      Patients included in the study were those who fulfilled the criteria for AE-IPF
      during the periods between April 1998 and June 2004 at Tosei General Hospital,
      and in whom NIV was introduced. Clinical data were obtained retrospectively from
      patient records. RESULTS: This study included 11 patients. The initial NIV
      settings were continuous positive airway pressure (CPAP) mode in 6 patients (mean
      10.1+/-2.5 cmH(2)O) and Spontaneous/Timed mode in 5 (mean inspiratory positive
      airway pressure/expiratory positive airway pressure; 15.0+/-3.3/10.2+/-2.9
      cmH(2)O). Five patients avoided intubation and survived more than 3 months after
      AE-IPF. Six patients who failed NIV died within 3 months. In these 6 patients, 4
      required intubation. The other 2 patients, who refused endotracheal intubation,
      died without intubation. Median survival time and 3-month survivals after acute
      exacerbation were 30 days, and 45.5%, respectively. CONCLUSION: Considering
      extremely poor prognosis of AE-IPF, our findings suggest that NIV is a viable
      option for the respiratory management in AE-IPF, and should be studied in a
      large, well-controlled trial.

PMID- 20686282
TI  - Peripheral arterial atherosclerosis in patients with extracranial, not
      intracranial, arterial stenosis.
AB  - BACKGROUND: It is not known whether stroke patients with intracranial stenosis
      often have lower extremity atherosclerosis. The aim of our study was to elucidate
      this issue. METHODS: Consecutive stroke patients who had cerebral angiography
      were prospectively enrolled in this study. Cerebral artery and lower extremity
      artery stenoses were evaluated simultaneously using conventional angiography. To
      investigate sub-clinical arteriosclerosis, duplex ultrasonography was performed
      to assess the maximal intima media thickness (IMT) of the common carotid artery
      (CCA) and the femoral artery, and the ankle brachial pressure index (ABI) was
      determined. The patients were classified into three groups based on the cerebral
      angiographic findings: 1) IS group, with a > or = 50% stenosis of the
      intracranial artery; 2) ES group, with a > or = 50% of the extracranial carotid
      artery; 3) NS group, with no stenosis. We compared the IMT of the CCA and the
      femoral artery, as well as the ABI, among the three groups. RESULTS: A total of
      81 patients (mean age 63 +/- 13 years old; 61 males) were enrolled. The
      prevalence of hypertension was greatest in the ES group. The maximal IMT of the
      femoral artery was highest in the ES group (ES group, 2.1 +/- 1.0 mm; IS group,
      1.5 +/- 0.7 mm; NS group, 1.7 +/- 0.9 mm; p=0.043). The ES group had the lowest
      ABI (ES group, 1.00 +/- 0.24; IS group, 1.11 +/- 0.17; NS group, 1.13 +/- 0.15,
      p=0.031). CONCLUSION: The presence of sub-clinical atherosclerosis of the lower
      extremity arteries differed between patients with intracranial and extracranial
      stenosis. The mechanism of atherosclerosis may differ between intracranial and
      extracranial internal carotid artery.

PMID- 20686283
TI  - Patients' preferences for doctors' attire in Japan.
AB  - OBJECTIVE: Physicians' attire is one important factor to enhance the physician
      patient relationship. However, there are few studies that examine patients'
      preferences for physicians' attire in Japan. We sought to assess patients'
      preference regarding doctors' attire and to assess the influence of doctors'
      attire on patients' confidence in their physician. Furthermore, we examined
      whether patients' preferences would change among various clinical situations.
      METHODS: Employing a cross-sectional design, Japanese outpatients chosen over one
      week in October 2008 from waiting rooms in various outpatient departments at St.
      Luke's International Hospital, Tokyo, were given a 10-item questionnaire. A 5
      point Likert scale was used to estimate patient preference for four types of
      attire in both male and female physicians, including semi-formal attire, white
      coat, surgical scrubs, and casual wear. In addition, a 4-point Likert Scale was
      used to measure the influence of doctors' attire on patient confidence. PATIENTS:
      Japanese outpatients consecutively chosen from waiting rooms at St. Luke's
      International Hospital in Tokyo for one week in October 2008. RESULTS: Of 2,272
      outpatients enrolled, 1483 (67.1%) of respondents were women. Mean age of
      subjects was 53.8 years (SD 16.2 years). Respondents most preferred the white
      coat (mean rank: 4.18, SD: 0.75) and preferred casual attire the least (mean
      rank: 2.32, SD: 0.81). For female physicians, 1.4% of respondents ranked the
      white coat little/least preferred while 64.7% of respondents ranked casual wear
      little/least preferred. Among respondents who most preferred the white coat for
      physician attire, perceived hygiene (62.7%) and inspiring confidence (59.3%) were
      important factors for doctor's attire. Around 70% of all respondents reported
      that physicians' attire has an influence on their confidence in their physician.
      CONCLUSION: This study confirms that Japanese outpatients prefer a white coat.
      Furthermore, this study strongly suggests that wearing a white coat could
      favorably influence patients' confidence in the relationship with their physician
      in all types of practice.

PMID- 20686284
TI  - Adenocarcinoma involving the whole pancreas with multiple pancreatic masses.
AB  - A 77-year-old man was referred to our hospital for further investigation of
      pancreatic masses. Imaging studies revealed hypovascular masses in the pancreatic
      head and body. Total pancreatectomy was performed under the diagnosis of double
      primary pancreatic carcinomas. Macroscopic examination revealed 3 nodules: one
      each in the pancreatic head, body, and tail. Microscopically, all 3 lesions
      showed similar carcinoma cells, which communicated with each other via the
      intraductal component, indicating a single large tumor. Incidentally, we also
      identified an adenocarcinoma of the common bile duct (CBD). The final diagnosis
      was synchronous double cancer involving the whole pancreas and the CBD.

PMID- 20686285
TI  - A case report of benign schwannoma of the liver.
AB  - Benign schwannoma is a very rare confronted entity in the liver. Only a very few
      cases have been reported in the medical literature. A 56-year-old woman was
      admitted to our hospital with epigastric pain. In the computed tomography scan a
      cystic mass was observed in the liver. The mass was resected with a prediagnosis
      of hydatid cyst; intraoperatively a 15x10x10 cm mass filled with hemorrhagic
      fluid was found. The histological examination confirmed the diagnosis of a benign
      schwannoma, proven by verocay bodies and a positive immunoreaction with the
      neurogenic marker S-100 protein.

PMID- 20686286
TI  - Toxic hepatitis induced by show-wu-pian, a Chinese herbal preparation.
AB  - Herbal preparations are widely available and often regarded by the public as
      harmless remedies for a variety of medical ailments. However, some of these
      products or their metabolites can cause adverse effects such as liver damage. In
      this case report a 53-year-old female taking shou-wu-pian for 8 months presented
      with acute hepatitis. Histopathological assessment of liver tissue obtained by
      biopsy was consistent with a toxic reaction. Clinical and biochemical resolution
      was brought about following cessation of the drug. It is important for clinicians
      to consider Chinese herbal preparations as a potential cause of abnormal liver
      function test results.

PMID- 20686287
TI  - Undiagnosed collecting duct carcinoma presenting as meningeal carcinomatosis and
      multiple bone metastases.
AB  - A 54-year-old woman presented with blepharoptosis, numbness in the lower lip,
      dysgeusia and pain in the extremities and back. MRI showed marked meningeal
      thickening and multiple bone lesions accompanying a prominent enhancing effect.
      CT scan of the chest and abdomen appeared to be unremarkable for primary cancer.
      She died 3 months after the admission, and postmortem autopsy showed a mass of
      about 2.5 cm in diameter in the renal medulla. Histological examination including
      immunohistochemistry confirmed the presence of a collecting duct carcinoma (CDC).
      This case is of particular interest because it emphasizes the possible fulminate
      clinical course of a small CDC.

PMID- 20686288
TI  - Pneumatosis cystoides intestinalis induced by the alpha-glucosidase inhibitor
      miglitol.
AB  - Pneumatosis cystoides intestinalis (PCI) is a rare condition in which pneumocysts
      develop in the submucosa or subserosa of the colon. We report herein a case of
      PCI induced by the alpha-glucosidase inhibitor (alphaGI) miglitol. There have
      been 9 recorded cases of PCI induced by other alphaGIs, but this is the first
      report of miglitol causing PCI. The PCI lesions in our case were smaller than
      those induced by voglibose or acarbose. The possibility of PCI should be
      considered in diabetic patients on alphaGI therapy who complain of
      gastrointestinal symptoms, and the gastrointestinal tract should be thoroughly
      investigated in these patients.

PMID- 20686289
TI  - Very late bare metal stent thrombosis presenting with acute myocardial
      infarction: 14 years after coronary stenting.
AB  - Fourteen years previously, a 67-year-old man underwent percutaneous coronary
      intervention (PCI) for proximal left anterior descending artery lesion with a
      bare metal stent (BMS) for acute myocardial infarction (AMI) and attained an
      excellent result. Ticlopidine (200 mg) was administered for one month and 100 mg
      of aspirin was daily has been continued. One year after PCI, coronary angiography
      showed no restenosis. However, 14 years after PCI, he suffered from AMI due to
      stent thrombosis. Intracoronary aspiration thrombectomy and implantation of a
      drug-eluting stent were successful. This report demonstrates evidence of a very
      late case of stent thrombosis with the use of BMS.

PMID- 20686291
TI  - Long-term suppressive effect of octreotide on progression of metastatic
      gastrinoma with multiple endocrine neoplasia type 1: seven-year follow up.
AB  - A 30-year-old woman had a history of prolactinoma and primary
      hyperparathyroidism. She was diagnosed as having multiple endocrine neoplasia
      type 1 with gastrinoma and liver metastases. Octreotide therapy was started and
      the serum gastrin level decreased immediately. Octreotide continued to suppress
      gastrin secretion over the next 7 years. The Ki67/MIB1 proliferation index of
      this tumor was only 0.5 % and somatostatin receptor (SSTR) 2 expression was very
      strong in both 2002 and 2009. This case suggests the importance of investigating
      the Ki67/MIB1 index and SSTR expression in patients with metastatic gastrinoma.

PMID- 20686290
TI  - Hypoglycemic coma in a patient with anorexia nervosa coincident with acute
      exacerbation of liver injury induced by oral intake of nutrients.
AB  - A 33-year-old woman with anorexia nervosa was admitted because of severe
      malnutrition. Acute liver injury was observed soon after the beginning of oral
      intake. She was prohibited from eating for 10 days and treated with parenteral
      nutrition until liver dysfunction was improved. One week after resuming oral
      intake, she presented severe hypoglycemic coma along with acute exacerbation of
      hepatocytic injury. Clinical laboratory data suggest that insufficient
      gluconeogenesis in acute liver injury was involved in severe hypoglycemia. We
      should be careful of severe hypoglycemia in patients with anorexia nervosa after
      resuming oral ingestion when signs of liver damage are detected, although
      hypoglycemic coma is uncommon in anorexia nervosa.

PMID- 20686292
TI  - Lymphocytic hypophysitis with a long latent period from onset of central diabetes
      insipidus to development of pituitary enlargement.
AB  - A 61-year-old man presented with central lymphocytic hypophysitis. Initial
      pituitary MRI imaging was normal, except for loss of the "bright spot" of the
      posterior lobe. A diagnosis of idiopathic diabetes insipidus was made. Two years
      later, pituitary gland enlargement with panhypopituitarism was detected. Eight
      months after commencing a replacement dose of corticosteroid, the pituitary
      enlargement was reduced in size. These findings resulted in a diagnosis of
      lymphocytic hypophysitis. In patients with idiopathic diabetes insipidus, it is
      important to suspect lymphocytic hypophysitis and to perform a long follow-up to
      repeat endocrinological examinations and pituitary imaging.

PMID- 20686293
TI  - Giant malignant insulinoma which developed from a non-functioning pancreatic
      tumor over a long period of time.
AB  - Insulinomas are the most common hormone-producing pancreatic neuroendocrine
      tumors (NETs), which are usually benign, solitary and small. We describe herein a
      patient with a giant insulinoma (>10 cm in diameter) with concomitant thyroid
      tumor as detected by Somatostatin receptor scintigraphy (SRS). A 50-year-old man
      presented hypoglycemic symptoms 20 years after the first detection of a
      pancreatic tumor, which was ameliorated by administration of a somatostatin
      analogue, octreotide. SRS showed abnormal uptake by the insulinoma as well as by
      the thyroid tumor. RT-PCR and immunohistochemical study revealed abundant
      expression of somatostatin receptor (SSTR)-1, -2, and -5 in his insulinoma and
      SSTR-1 and -2 in his thyroid follicular neoplasm. This is a rare case of a slow
      growing pancreatic well-differentiated neuroendocrine carcinoma over a long
      period of time to become a symptomatic giant insulinoma. Furthermore, SRS proves
      to be a useful tool for localization of insulinoma as well as concomitant thyroid
      neoplasm with predominant expression of SSTRs.

PMID- 20686294
TI  - Central diabetes insipidus and hypothalamic hypothyroidism associated with
      aceruloplasminemia.
AB  - Aceruloplasminemia is a rare autosomal recessive disease first reported by
      Miyajima et al. (Neurology 37: 761-767, 1987); it is clinically characterized by
      diabetes mellitus, retinal degeneration and neurological abnormalities, such as
      cerebellar ataxia, extrapyramidal signs and dementia. Aceruloplasminemia is
      caused by mutations in the ceruloplasmin gene, which results in the absence of
      serum ceruloplasmin and iron overload in the brain, liver, pancreas and other
      organ tissues. However, little is known about endocrine diseases associated with
      aceruloplasminemia. We report herein a case of aceruloplasminemia accompanied by
      central diabetes insipidus and hypothalamic hypothyroidism.

PMID- 20686295
TI  - Successful treatment with rituximab in a patient with TTP secondary to severe
      ANCA-associated vasculitis.
AB  - We report a case of thrombotic thrombocytopenic purpura (TTP) secondary to
      antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis treated by
      rituximab. TTP secondary to ANCA-associated vasculitis is very rare and has a
      high mortality rate. We employed rituximab and successfully treated TTP secondary
      to ANCA-associated vasculitis, because standard therapies, such as steroid
      therapy, intravenous pulse cyclophosphamide, and repeated plasma exchange (PE),
      did not suppress her disease activity. This is the first report to suggest that
      rituximab can achieve complete remission of TTP secondary to ANCA-associated
      vasculitis.

PMID- 20686296
TI  - IgG4-related chronic tubulointerstitial nephritis without autoimmune pancreatitis
      and the time course of renal function.
AB  - We report an elderly man with chronic tubulointerstitial nephritis (TIN) showing
      a high serum immunoglobulin G4 (IgG4) concentration. His serum creatinine (Scr)
      level had gradually increased from 0.9 mg/dL to 5.6 mg/dL over 18 months. Renal
      biopsy showed marked IgG4-positive plasma cell infiltration in the interstitium
      without glomerular abnormalities and IgG4-related TIN was diagnosed. Oral
      prednisolone reduced his Scr and IgG4 levels immediately. The present case
      indicates that IgG4-related TIN can not only progress rapidly but also
      chronically over a long period without significant urinary abnormalities, and we
      should consider hidden IgG4-related TIN in cases of chronic renal insufficiency.

PMID- 20686297
TI  - Pathological findings and pulmonary dysfunction after acute respiratory distress
      syndrome for 5 years.
AB  - We report the pathological findings of the lung after acute respiratory distress
      syndrome (ARDS), and pulmonary function tests during five years of follow-up. A
      39-year-old woman, treated for acute myelogenous leukemia, developed ARDS. She
      recovered from ARDS but suffered from pulmonary aspergillosis. Her aspergilloma
      was removed surgically. Her lung function tests and diffusing capacity of the
      lung for carbon monoxide (DL(CO)) improved but diffusion impairment remained five
      years after recovery. Pathological examination of the resected material showed
      sclerosis in lobular septa and scattered fibrosis in alveolar ducts except for
      the aspergillosis. These fibrotic changes may be causally associated with her
      loss of DL(CO).

PMID- 20686298
TI  - Organizing pneumonia with a positive result for anti-CCP antibodies as the first
      clinical presentation of rheumatoid arthritis.
AB  - We report an 86-year-old woman who presented with organizing pneumonia (OP) with
      a positive anti-cyclic citrullinated peptide (anti-CCP) antibodies as the first
      manifestation of rheumatoid arthritis (RA). She experienced dyspnea, chest X-ray
      showed diffuse alveolar exudates indicated OP histologically. Although she did
      not present with articular symptoms initially, anti-CCP antibodies measured for
      differentiation of RA were positive. Eight months later, she showed
      representative manifestations of RA. Even though OP following joint involvement
      is frequent in RA, in rare cases it could be the first manifestation. This is the
      first case showing OP with a positive result for anti-CCP antibodies as the first
      manifestation of RA.

PMID- 20686299
TI  - Sarcoidosis in a patient with systemic sclerosis and primary biliary cirrhosis.
AB  - A 73-year-old woman who had been diagnosed with systemic sclerosis was admitted
      for further examination of bilateral hilar lymphadenopathy. Sarcoidosis was
      confirmed based on elevated serum levels of angiotensin-converting enzyme, a high
      proportion of lymphocytes and a high CD4/CD8 ratio in bronchoalveolar lavage
      fluid, abnormal (67)Gallium uptake in the mediastinum and noncaseating granulomas
      in skin biopsy specimens. In addition, high levels of antimitochondrial M2
      antibodies and alkaline phosphatase indicated primary biliary cirrhosis (PBC).
      Here we describe a rare triplex of sarcoidosis, SSc and PBC. Although the
      etiology of this complex remains unknown, these three diseases might share some
      pathogenesis.

PMID- 20686300
TI  - Endobronchial metastasis from prostate cancer mimicking primary lung cancer.
AB  - Endobronchial metastasis from prostate cancer is a rare neoplasm which
      metastasizes to the proximal central or subsegmental bronchus, in a
      bronchoscopically visible range. We present a 72-year-old man with a left
      superior lobar bronchus mass, intrapulmonary metastases, and bone metastases,
      mimicking primary lung bronchogenic carcinoma. Increasing tPSA, decreasing
      fPSA/tPSA level, and prostatic puncture pathology proved prostate cancer.
      Pathomorphology and immunohistochemistry of the mucosa specimen with P504S, PSA
      revealed the diagnosis of pulmonary metastases from prostate cancer. The patient
      was treated by hormonal treatment and chemotherapy. He was in remission thirteen
      months after diagnosis.

PMID- 20686301
TI  - A case of pulmonary nodular lymphoid hyperplasia with a resected cavity, followed
      by spontaneous regression of the remaining lesions.
AB  - A 50-year-old man was admitted to our hospital for examination of an abnormal
      shadow on chest radiography. Computed tomography revealed multiple small nodular
      shadows in bilateral lung fields, with cavitation in a right S3 lesion that was
      resected by video-assisted thoracoscopic surgery. Histopathological examination
      revealed marked proliferation of lymphoid tissue, including many plasma cells
      that were polyclonal in nature. This case was considered to be pulmonary nodular
      lymphoid hyperplasia (PNLH). Several residual nodules spontaneously disappeared
      during the 6 years of follow-up. This was a rare case of PNLH with a resected
      cavity, followed by spontaneous regression of the remaining lesions.

PMID- 20686302
TI  - A case of McArdle disease: efficacy of vitamin B6 on fatigability and impaired
      glycogenolysis.
AB  - McArdle disease is a glycogenetic myopathy caused by a deficit of
      myophosphorylase inherited in an autosomal recessive pattern. Here, we report a
      case of McArdle disease in which fatigability was the only subjective complaint.
      Objective neurological findings were normal except for very mild muscle weakness
      in limbs and an elevated serum creatine kinase level. Ischemic forearm exercise
      test showed deficient glycogenolysis. In the muscle biopsy specimen, periodic
      acid Schiff (PAS) stained subsarcolemmal glycogen was increased and the muscle
      phosphorylase A activity was decreased. After administration of vitamin B6,
      fatigability was diminished and ischemic forearm exercise test showed improved
      glycogenolysis. Vitamin B6 may be beneficial for McArdle disease, especially for
      its easy fatigability.

PMID- 20686303
TI  - A case of atypical amyloid polyneuropathy with predominant upper-limb involvement
      with the diagnosis unexpectedly found at lung operation.
AB  - We present a patient of familial amyloid polyneuropathy (FAP) with predominant
      upper-limb involvement, the pattern of which resembled a mononeuropathy multiplex
      pattern. Sural nerve biopsy failed to diagnose the disorder, but lung partial
      resection performed later for other diagnostic purposes suggested FAP. A rare
      mutation in the transthyretin gene (S50R) was subsequently confirmed. Diagnostic
      challenges of FAP with atypical clinical presentations, including difficulties in
      pathological diagnosis, are discussed with a review of the literature.

PMID- 20686304
TI  - Isolated proximal leg paresis due to a small cortical infarction.
AB  - We describe two patients with small cortical infarcts, who presented with
      isolated proximal weakness in one of their legs. These lesions were located in
      the contralateral precentral gyrus, more medial than the precentral knob, but
      more lateral than the topmost part of the motor cortex. These clinical findings
      are consistent with the physiological findings of Penfield and Boldrey, and those
      of recent activation studies by functional MRI. It is clinically important to pay
      close attention to the contralateral top of the motor cortex when examining pure
      motor monoparesis of a proximal part of a lower extremity.

PMID- 20686305
TI  - Epigenetic inactivation of tumor suppressor SFRP2 and point mutation in KRAS
      proto-oncogene in fistula-associated mucinous type anal adenocarcinoma: report of
      two cases.
AB  - The secreted frizzled-related proteins (SFRPs) genes are unmethylated in normal
      colorectal mucosa tissue but aberrant methylation profiles can be detected in
      colorectal cancer (CRC), adenomas, and in aberrant crypt foci. The aim of the
      current study was to clarify whether SFRP2 methylation and K-ras structural
      mutation in fecal DNA can be found in stool and tumoral tissues of individuals
      with fistula-associated mucinous type anal adenocarcinomas (MTAA).Two man
      patients (68 and 56 years old) were treated for anorectal fistula in the surgical
      department. Patients were evaluated for clinical findings, tumoural tissue
      samples were examined histopathologically and DNA from fecal and tumoral tissue
      samples were isolated. K-ras mutation and promoter hypermethylation of SFRP2 gene
      in tumoral tissues were assessed by methylation-specific PCR based stripAssay
      hybridisation technique (Me-PCR) and compared to the healthy controls. Fecal and
      tumoural tissue samples from both patients were found to be fully hypermethylated
      profiles for SFRP2 gene and combined point mutations were detected in codon 12
      and 13 of K-ras proto-oncogene. The current results showed that the combined
      effects of somatic mutations in K-ras and epigenetic alterations in SFRP2 genes
      may play an active role in the development of mucinous type anal adenocarcinoma.

PMID- 20686306
TI  - Polymyalgia rheumatica as the first presentation of metastatic lymphoma.
AB  - A 48-year-old HIV-positive woman presented with progressive pain and stiffness of
      both shoulders and hips. She was given the diagnosis of polymyalgia rheumatica
      (PMR) due to high erythrocyte sedimentation rate. However, a 1-week course of
      prednisolone failed to improve her symptoms. She later discovered a breast lump
      of which histopathological tissue was consistent with a diffuse large B-cell
      lymphoma. Whole body bone scan revealed multiple bony metastases. The presence of
      atypical features of PMR and lack of dramatic response to steroids should prompt
      physicians to raise the probability of differential diagnoses other than PMR, and
      in particular, malignancy.

PMID- 20686307
TI  - Paragonimus westermani found in the tip of a little finger.
AB  - Paragonimiasis is the infestation of lung flukes of the trematode genus
      Paragonimus. Because the symptoms and radiologic findings of paragonimiasis mimic
      those of tuberculosis, some patients with paragonimiasis are initially treated
      for tuberculosis. Although Paragonimus may also reach ectopic sites such as the
      peritoneum or brain, infection in the skin is rare. To our knowledge,
      paragonimiasis has not been found in the tip of a finger. We report a case of 39
      year-old woman who was belatedly diagnosed as having paragonimiasis with a
      parasitic migration to the tip of the left little finger after initial
      misdiagnosis of tubercular serositis.

PMID- 20686308
TI  - Recurrent respiratory papillomatosis arising in trachea not affecting larynx.
AB  - Recurrent respiratory papillomatosis (RRP) is an infrequent benign neoplasm
      commonly involving the upper respiratory tract with laryngeal predilection. The
      diagnosis and treatment of this disease are challenging due to its nonspecific
      clinical presentations and recurrent nature. We report here a rare juvenile case
      of RRP arising in the trachea without laryngeal lesions. Our experiences indicate
      that a high awareness of RRP and proper consideration in the right clinical
      context are prerequisites for early diagnosis, and a combination of multiple
      treatment modalities should be considered as a feasible treatment regimen.

PMID- 20686309
TI  - Purulent pericarditis due to Streptococcus pneumoniae diagnosed by pneumococcal
      urinary antigen assay and 16S rDNA sequence of the pericardial fluid.
AB  - A 57-year old woman was admitted to our hospital with massive pericardial fluid.
      Culture of the pericardial fluid was negative, however, Binax NOW Streptococcus
      pneumoniae urinary antigen test was positive in pericardial fluid. 16S rDNA
      sequencing and PCR for lyt(A) gene of the pericardial fluid sample confirmed the
      microbiological diagnosis of S. pneumoniae. The patient was treated with surgical
      drainage and continuous intravenous infusion of penicillin G and its
      concentration in the serum and pericardial effusion was monitored. Incorporation
      of molecular methods such as antigen testing and nucleic acid sequencing would
      benefit the management of infectious diseases especially in culture negative
      cases.

PMID- 20686310
TI  - A rare case of group A streptococcal endocarditis with absence of valvular
      vegetation.
AB  - Group A streptococcal endocarditis has been described in intravenous drug
      misusers and as a post-varicella infection in children. We report a 64-year-old
      man with no prior risk factors who presented with a persistent fever, malaise,
      polyuria and cola-colored urine. On examination peripheral stigmata of
      endocarditis without a cardiac murmur and asymptomatic pharyngeal exudates were
      found. Blood and urine analysis revealed renal failure from suspected
      glomerulonephritis. Blood cultures revealed fully sensitive Group A streptococci.
      Transthoracic and transesophageal echocardiographies revealed no vegetation. The
      Modified Duke's Criteria aided in the diagnosis of definite infective
      endocarditis, despite the absence of valvular vegetation.

PMID- 20686311
TI  - Mantle cell lymphoma presenting with a tumor of the hard palate.
AB  - We report a 71-year-old man with a disseminated disease of mantle cell lymphoma
      (MCL). He initially noticed instability of the maxillary denture due to swelling
      of the hard palate. Combined positron-emission tomography and computed tomography
      demonstrated a marked accumulation of fluorodeoxyglucose in the palate. A biopsy
      of the palatine tumor disclosed diffuse infiltrates of lymphoid cells, which were
      positive for CD20 and cyclin D1. The peripheral blood contained lymphoma cells
      with the characteristic immunophenotype, and fluorescence in situ hybridization
      detected fusion signals indicative of t(11;14)(q13;q32). In a literature review
      we identified only three cases of MCL with palatine involvement to date.

PMID- 20686312
TI  - Severe pneumonia caused by a novel influenza A (H1N1) virus in an asymptomatic
      emphysematous smoker.
AB  - A 49-year-old female presented with diarrhea and a high fever followed by
      progressive dyspnea. Until this presentation, she had been healthy except for
      chronic dyspepsia and diarrhea. She had a smoking habit of 15 pack-years.
      Laboratory tests revealed lymphopenia, hypoalbuminemia and hypogammaglobulinemia.
      A rapid influenza test in combination with an RT-PCR assay revealed the presence
      of the novel influenza A (H1N1) virus. Chest computed tomography revealed
      centrilobular emphysema. This report suggests that regular smoking may become a
      risk for severe pneumonia in patients presenting with the novel influenza A
      (H1N1) virus, when accompanying asymptomatic emphysema is combined with other
      problems such as hypoalbuminemia and hypogammaglobulinemia.

PMID- 20686313
TI  - Augmentation of J wave following ventricular pause in "benign" early
      repolarization.

PMID- 20686314
TI  - A rare pericardial cyst resembling hydatid cyst on echocardiography.

PMID- 20686315
TI  - Cholesterol deposition around small joints of the hands in familial
      hypercholesterolemia mimicking "Bouchard's and Heberden's nodes" of
      osteoarthritis.

PMID- 20686316
TI  - Reversed halo sign associated with dermatomyositis.

PMID- 20686317
TI  - Extramedullary plasmacytoma as an uncommon cause of gastrorrhagia.

PMID- 20686318
TI  - Interstitial pulmonary hemorrhage along the pulmonary artery secondary to
      ruptured aortic dissection.

PMID- 20686319
TI  - Pulmonary sequestration diagnosed by three-dimensional reconstruction computed
      tomography.

PMID- 20686320
TI  - Susac syndrome.

PMID- 20686321
TI  - Retroperitoneal fibrosis secondary to pergolide therapy.

PMID- 20686322
TI  - Sleep complaints in hospitalized Italian patients with hematological
      malignancies.

PMID- 20686325
TI  - Beneficial effects of mild stress (hormetic effects): dietary restriction and
      health.
AB  - Hormesis is defined as a dose-response phenomenon characterized by low-dose
      stimulation and high-dose inhibition, and has been recognized as representing an
      overcompensation for mild environmental stress. The beneficial effects of mild
      stress on aging and longevity have been studied for many years. In experimental
      animals, mild dietary stress (dietary restriction, DR) without malnutrition
      delays most age-related physiological changes, and extends maximum and average
      lifespan. Animal studies have also demonstrated that DR can prevent or lessen the
      severity of cancer, stroke, coronary heart disease, autoimmune disease, allergy,
      Parkinson's disease and Alzheimer's disease. The effects of DR are considered to
      result from hormetic mechanisms. These effects were reported by means of various
      DR regimens, such as caloric restriction, total-nutrient restriction, alternate
      day fasting, and short-term fasting. Mild dietary stress, including restriction
      of amount or frequency of intake, is the essence of DR. For more than 99% of
      their history, humans lived as hunter-gatherers and adapted to restrictions in
      their food supply. On the other hand, an oversufficiency of food for many today
      has resulted in the current global epidemic of obesity and obesity-related
      diseases. DR may be used, therefore, as a novel approach for therapeutic
      intervention in several diseases, when detailed information about effects of mild
      dietary stress on human health is obtained from clinical trials.

PMID- 20686324
TI  - Long-term effects of pioglitazone on carotid atherosclerosis in Japanese patients
      with type 2 diabetes without a recent history of macrovascular morbidity.
AB  - AIM: No previous studies have evaluated the long-term anti-atherosclerotic
      effects of pioglitazone in Asian patients with type 2 diabetes. Therefore, the
      present study investigated the protective effects of pioglitazone on the
      progression of carotid intima-media thickness (IMT), an established surrogate
      marker of cardiovascular events in Japanese type 2 diabetic patients without a
      recent history of cardiovascular morbidity. METHODS: This 2.5-4-year, randomized,
      open-label, blinded endpoint study was conducted in 6 centers across Japan.
      Patients received pioglitazone with or without other oral glucose-lowering drugs
      (excluding another thiazolidinedione) (n=89) or oral glucose-lowering drugs,
      excluding thiazolidinediones (n=97). Treatment was adjusted to achieve HbA(1c)
      <6.5%. The primary endpoints of the study were the absolute changes from the
      baseline to final visit in max- and mean-IMT in the average of bilateral common
      carotid arteries. RESULTS: Pioglitazone induced carotid IMT regression compared
      to baseline measurements (from 1.060 +/- 0.2368 to 0.992 +/- 0.1921 mm; p=0.0042
      in max-IMT and from 0.839 +/- 0.1873 to 0.780 +/- 0.1571 mm; p=0.0019 in mean
      IMT). Although the between-group difference did not reach statistical
      significance, the regression of carotid IMT values was greater in the
      pioglitazone-treatment group than in the non-pioglitazone group, (max-IMT: -0.069
      +/- 0.2199 mm vs -0.031 +/- 0.2327 mm, respectively; p=NS, mean-IMT: -0.058 +/-
      0.1718 mm vs -0.043 +/- 0.1644 mm, respectively; p=NS). CONCLUSIONS: Pioglitazone
      induced and maintained the long-term regression of carotid IMT in Japanese type 2
      diabetic patients. This suggests that pioglitazone may inhibit the progression of
      atherosclerosis in this patient group. Further studies are required to verify
      these findings.

PMID- 20686326
TI  - The Trp64Arg polymorphism of the beta3-adrenergic receptor gene is associated
      with weight changes in obese Japanese men: a 4-year follow-up study.
AB  - The aim of this study was to investigate whether the Trp64Arg polymorphism of the
      beta(3)-adrenergic receptor gene (ADRB3) is associated with weight changes in
      obese Japanese men at 4-year follow-up. The participants were 145 obese Japanese
      men [age: 35.8+/-5.3 y; body mass index (BMI): 27.5+/-3.3 kg/m(2)]. The
      participants were divided into two groups according to the Trp64Arg genotype: (1)
      with the Arg64 allele of the ADRB3 (Trp64Arg and Arg64Arg genotypes, n=50); (2)
      without the Arg64 allele of the ADRB3 (Trp64Trp genotype, n=95). The ADRB3
      genotyping was performed by denaturing high performance liquid chromatography
      (DHPLC). Body weight, BMI, and blood pressure were determined at baseline and at
      4 years. After 4 years, the participants with the Arg allele of the ADRB3
      significantly increased their body weight (2.1+/-4.7 kg, p=0.002) and BMI (0.64+/
      1.6 kg/m(2), p=0.006) whereas the participants without the Arg allele of the
      ADRB3 did not significantly change in these parameters (body weight: -0.36+/-4.2
      kg, p=0.41; BMI: -0.24+/-1.5 kg/m(2), p=0.12). The results in this study showed
      that the Arg allele of the ADRB3 is associated with long-term changes in body
      weight in obese individuals. This polymorphism may become an indicator in
      personalized weight loss programs in obese men.

PMID- 20686327
TI  - Seasonal variation in amount of unabsorbed dietary carbohydrate from the
      intestine after breakfast in young female Thai subjects: comparison with that of
      Japanese subjects.
AB  - Previously, using the breath hydrogen test, we investigated seasonal variations
      in the amount of unabsorbed dietary carbohydrate from the intestine after
      breakfast in female Japanese university students and young Polish subjects. In
      the study we found that there were significant seasonal variations in both
      countries with the smallest unabsorbed dietary carbohydrate in autumn and the
      biggest in winter. Considering the theory of human adaptation to living
      environments, we suggested a hypothesis that this seasonal variation in the
      efficiency of carbohydrate absorption in the intestine may reflect human
      adaptation and/or a response to seasonal change in the living environment. In
      order to prove this hypothesis, we carried out the same examination in Chiang
      Mai, Thailand, where there is different seasonal change in the living environment
      from that of Japan and of Poland. In this examination, we measured the amount of
      unabsorbed dietary carbohydrate (UDC) from the intestine after breakfast and the
      oro-cecal transit time (OCTT) of the breakfast in female Thai university students
      using the same method and experimental protocol as previously carried out with
      Japanese subjects. We conducted the examination in April (the hot season), in
      August-September (the rainy season), and in November-December (the dry season) of
      2008, at the Medical School of Chiang Mai University, Chiang Mai. The results are
      summarized as follows: (1) there were no significant seasonal variations in the
      amounts of unabsorbed dietary carbohydrate from breakfast in Thai subjects; (2)
      there were no significant seasonal variations in the oro-cecal transit times of
      breakfast or a soluble indigestible trisaccharide (lactosucrose) solution in Thai
      subjects; (3) there were no significant differences in the oro-cecal transit
      times of breakfast between the two countries in any season; (4) the UDC of Thai
      subjects was significantly less than that of the Japanese subjects in the three
      seasons. These results suggest that differences in seasonal change in a living
      environment have different effects on seasonal variations in the efficiency of
      carbohydrate absorption in the intestine after breakfast.

PMID- 20686328
TI  - The correlation between CVR-R and carotid atherosclerosis in type 2 diabetes
      mellitus patients with diabetic neuropathy.
AB  - We examined the relationship between the coefficient of variation in the R-R
      intervals (CVR-R) using electrocardiograms and the ultrasonic intima-media
      thickness (IMT) of the carotid artery, an atherosclerotic parameter, in type 2
      diabetes mellitus (DM) patients with diabetic neuropathy (n=47, males/females:
      29/18; mean age: 62 years). In this study, the CVR-R-related indexes, including
      CVR-R at rest (CVR-R(rest)), CVR-R with deep breaths (CVR-R(breath)) and their
      difference (CVR-R(breath) minus CVR-R(rest): CVR-R(dif)), were defined. Data such
      as body mass index, smoking habits, hemoglobin A1c, blood pressure, and serum low
      density lipoprotein were collected. A significant inverse correlation was
      observed between max-IMT and CVR-R(dif) (beta=-0.34, p=0.042), but not CVR
      R(rest) or CVR-R(breath), in multivariate analyses adjusted for all the data.
      Therefore, the CVR-R(dif) may serve as a clinical index for the diabetic
      autonomic neuropathy-atherosclerosis relation in type 2 DM patients.

PMID- 20686329
TI  - Toxic effect onset and evaluations of medicinal drugs--horizon for Darwinian
      toxicological thought.
AB  - The theory of Darwinian Medicine linked to an extension of Darwin's evolutionary
      theory is based on the approach from the aspect of "why we become ill?".This
      theory enables us to understand the relationship between humans and diseases by
      thinking from evolutional perspective, shows an important help for preventive
      medicine, and is meaningful to consider the future human healthcare. Toxicology
      has been defined as a research of adverse effect of xenobiotic substances backed
      up by diverse-sciences. Toxic effects are basically responses to xenobiotic
      substances, and expressed as triggering or additional accelerating adverse
      effects toward abnormal condition. Toxic effects, biological adverse responses,
      are interpreted as protective responses of living body, and the adverse effects
      caused by drugs are also considered to be protective responses. This logic can be
      translated as "Darwinian Toxicology" corresponding to "Darwinian Medicine",
      replying to "why we get into toxic condition by xenobiotics exposure". This paper
      refers to the meaning of toxic effects based on mechanisms underlying and
      comprehensive drug safety evaluation from Darwinian Medicine perspectives.

PMID- 20686330
TI  - Effects of preparation methods for multi-wall carbon nanotube (MWCNT) suspensions
      on MWCNT induced rat pulmonary toxicity.
AB  - Since there is a possibility of inhaling the fibers of multi-wall carbon nanotube
      (MWCNT) without any agglomeration, it is important that the pulmonary toxicity is
      evaluated by intratracheal instillation without agglomeration. MWCNT suspended in
      an artificial lung surfactant (ALS) with or without grinding in an agate mortar
      was instilled once intratracheally to rats to determine whether differences of
      the effects to pulmonary toxicity by different amounts of agglomerated MWCNT
      particle. The MWCNT suspension preparation method with grinding was effective at
      reducing agglomerates and in increasing uniform dispersion of the fibers. The
      ground MWCNT induced higher LDH levels and neutrophil ratios in the
      bronchoalveolar lavage fluid (BALF). There were no remarkable responses in rats
      in the non-ground MWCNT group, with the exception of inflammatory responses in
      the early phase. Some histopathological findings varied between rats given the
      ground MWCNT and non-ground MWCNT. A major difference was an MWCNT-laden
      macrophage infiltration site in the lung, which were in the alveolus in the
      ground MWCNT group, and in the interstitium in non-ground MWCNT group.
      Accordingly, the preparation method with grinding is considered to be effective
      at reducing agglomerates and ensuring uniform dispersion of the fibers. These
      findings lead us to conclude that the amount of agglomerates in the suspension is
      an important factor affecting the pulmonary toxicity of MWCNT.

PMID- 20686331
TI  - Pharmacological assessment of ARTCEREB irrigation and perfusion solution for
      cerebrospinal surgery using primary cultures of rat brain cells.
AB  - ARTCEREB irrigation and perfusion solution (Artcereb), an ethical pharmaceutical,
      is typically applied inside the skull and spinal cavity as artificial fluid.
      Artcereb is composed of glucose and electrolytes (Na+, K+, Mg2+, Ca2+, Cl-, HCO3-
      and P) and has a pH of 7.3. An in vitro assessment of the effects of Artcereb on
      cell culture of rat fetal astrocytes or rat fetal brain cells was performed in
      comparison with normal saline and lactated Ringer's solutions. Furthermore, the
      effects of Artcereb on cell culture of rat fetal brain cells were also assessed
      in comparison with Krebs bicarbonate solution. Cell function after exposure to
      Artcereb was assessed based on 3H-thymidine incorporation activity. Cell function
      after exposure to Artcereb and lactated Ringer's solution in primary cultures of
      rat fetal astrocytes remained unaffected when compared to that after exposure to
      normal saline. Cell function after exposure to Artcereb in a primary culture of
      rat brain cells remained unaffected as compared to that after exposure to normal
      saline and lactated Ringer's solution. However, function decreased after exposure
      to a modified Artcereb formulation lacking bicarbonate, thus confirming that the
      presence of bicarbonate is essential for the Artcereb formulation.

PMID- 20686332
TI  - Pharmacokinetic study of sulbactomax.
AB  - We have evaluated pharmacokinetics of a fixed dose combination (FDC) of
      ceftriaxone and sulbactam (2:1) or sulbactomax in eight healthy volunteers. A 1.5
      g dose of sulbactomax, 1 g dose of ceftriaxone and 0.5 g sulbactam were given
      intravenously in a balanced two-ways cross-over study. Serially collected plasma
      sample was analyzed for ceftriaxone and sulbactam by high performance liquid
      chromatography (HPLC). The mean peaks of ceftriaxone and sulbactam concentrations
      in plasma were 152.06+/-6.65 microg/ml and 21.32+/-1.80 microg/ml, respectively
      and plasma half-lives for ceftriaxone and sulbactam were 5.2+/-0.35 hr and 0.94+/
      0.038 hr, respectively. The AUC0-24 for ceftriaxone and sulbactam was 760.16+/
      27.68 microg.hr/ml and 20.74+/-2.34 microg.hr/ml, respectively, with elimination
      rate constant of 0.133+/-0.009 hr(-1) and 0.732+/-0.029 hr(-1), respectively. The
      kinetics of ceftriaxone and sulbactum did not change in combination as compared
      to the alone treatment. Also, concentration of the ceftriaxone after 24 hr is
      higher than the minimum inhibitory concentration (MIC) of the most of the gram
      positive and gram negative bacteria indicating that one dose in a day is
      sufficient to treat the disease caused by these organisms.

PMID- 20686333
TI  - Differential sensitivity and responsiveness of three human cell lines HepG2,
      1321N1 and HEK 293 to cadmium.
AB  - Cadmium (Cd) is a toxic heavy metal with no uniform mechanism of toxicity. In
      this the present study, the toxic effect of 5, 10 and 50 microM of Cd chloride
      was compared in three human cell lines; a human hepatoma cell line HepG2, a human
      astrocytoma cell line 1321N1, and a human embryonic kidney cell HEK 293. The
      results indicate a decrease in the viability of all three cell lines following
      exposure to Cd with HepG2 cells (IC50=13.96 microM) showing the most sensitivity
      when measured using the MTT assay. There was significant increase in lactate
      dehydrogenase leakage, DNA damage, malondialdeyde and antioxidant enzymes
      activities in all three cell lines especially at 50 microM Cd. Significant
      decreases in ATP production were also observed at all Cd concentrations in HepG2
      and HEK 293 cell lines. ROS levels significantly increase and GSH/GSSG ratio
      significantly decrease in all the three cell lines after Cd exposure, but these
      effects were attenuated by the presence of N-acetylcysteine (NAC). The present
      study therefore shows that ROS production and glutathione (GSH) depletion may
      play a role in Cd-induced toxicity in all the three cell lines. The endogenous
      levels of protective enzymes as well as their responsiveness are likely to
      determine a cell's susceptibility to Cd.

PMID- 20686334
TI  - Sub-acute toxicity study of a new aminoglycoside etimicin sulphate in swiss
      albino mice.
AB  - Etimicin sulfate, an ethylization derivative of gentamicin, is a new soluble wide
      spectrum synthetic aminoglycoside drug. It has wide antibacterial spectrum with
      high effect and less cross resistance as compared to other aminoglycosides. In
      order to further explore its safety and tolerance, we have conducted a subactute
      toxicity study on swiss albino mice. Results from the present study have
      elucidated that treatment of etimicin sulfate exerts no significant signs of
      toxicity at any dose level used in the study. Physiological as well as
      hematological parameters were unaltered throughout the study. Biochemical
      examination and histopathology of all organs confirmed no significant alteration
      at any dose levels. The result of this study has suggested there was no obvious
      toxicity observed with the treatment of etimicin sulphate. It was found to be a
      safe alternative for various severe infections.

PMID- 20686335
TI  - Tissue accumulation and urinary excretion of chromium in rats fed diets
      containing graded levels of chromium chloride or chromium picolinate.
AB  - To attempt a risk assessment of the excess intake of trivalent chromium (Cr),
      tissue Cr accumulation and urinary Cr excretion were examined in weanling rats
      fed experimental diets containing graded levels of Cr chloride (CrCl3) or Cr
      picolinate (CrPic). Thirty-six male weanling 4-weeks-old Wistar rats were divided
      into six groups and fed a casein-based semi-purified diet (Cr content: <0.02
      microg/g) supplemented with 1, 10, or 100 microg Cr/g as CrCl3 or CrPic for 28
      days. Among the experimental groups, no significant difference was observed in
      body weight; however, supplementation of 100 microg Cr/g to the diets caused a
      significant low liver weight irrespective of the chemical species of Cr.
      Activities of serum aspartate aminotransferase and alanine aminotransferase were
      significantly elevated in rats given CrPic at 100 microg Cr/g. In the liver,
      kidney and femur, Cr accumulation increased with elevation of the dietary Cr
      level. No influence of the difference in the chemical species of supplemented Cr
      was observed in the liver and kidney, but CrCl3 caused significantly higher Cr
      accumulation than CrPic in the femur of rats given 100 microg Cr/g. Daily urinary
      Cr excretion elevated with the increase of the dietary Cr level. Rats given CrPic
      showed significantly higher daily urinary Cr excretion than those given CrCl3,
      particularly at a dietary Cr level of 100 microg/g. The rate of urinary Cr
      excretion in rats given CrPic was constant, irrespective of the dietary Cr level,
      but that of rats given CrCl3 fell with the increase of the dietary Cr level.
      These results indicate that the lowest adverse effect level of dietary Cr is less
      than 100 microg/g, irrespective of the chemical species of Cr.

PMID- 20686336
TI  - Ninety-day oral toxicity study of rhamsan gum, a natural food thickener produced
      from Sphingomonas ATCC 31961, in Crl:CD(SD)IGS rats.
AB  - This study was designed to evaluate and characterize any subchronic toxicity of
      rhamsan gum, a polysaccharide produced from Sphingomonas strain ATCC 31961, when
      administered to both sexes of Crl:CD(SD)IGS rats at dietary levels of 0
      (control), 0.5, 1.5, and 5.0% (10 rats/sex/group). During the study, the
      treatment had no adverse effects on clinical signs, survival, body weights and
      food and water consumption, or on findings of urinalysis, ophthalmology,
      hematology, or blood biochemistry. Examination of gross pathology and
      histopathology exhibited no differences of toxicological significance between
      control and treated rats. Increased relative cecum (filled) and cecum (empty)
      weights, evident in males of 1.5% group and both sexes of the 5.0% group, were
      considered to be a physiological adaptation. Thus, the results indicated the
      toxic level of rhamsan gum to be more than 5.0%, and the no-observed-adverse
      effect level (NOAEL) was concluded to be 5.0% (3,362 mg/kg body weights/day for
      males, and 4,304 mg/kg body weights/day for males) from the present study.

PMID- 20686337
TI  - Effects of erlotinib on lung injury induced by intratracheal administration of
      bleomycin (BLM) in rats.
AB  - Interstitial lung disease has been reported in cancer patients treated with
      epidermal growth factor receptor tyrosine kinase inhibitors, erlotinib and
      gefitinib. Preclinical safety studies with erlotinib did not show any evidence
      for an induction of injury on intact lungs in rats and dogs. In the present
      study, we investigated the effects of erlotinib on lung injury induced by
      intratracheal administration of bleomycin (BLM) in rats. In Experiment 1, we
      examined the effects of short-term (7- and 21-day) administration of erlotinib
      (10 mg/kg/day, p.o.; subtoxic dose) on the BLM (0.1 or 0.6 mg/rat)-induced lung
      injury of slight and moderate severity. In Experiment 2, we examined the effects
      of long term (up to 63-day) administration of higher-dose (up to 20 mg/kg/day;
      toxic dose; accompanied with decreased body weight gain and severe skin lesions)
      erlotinib on the BLM-induced lung injury. In rats receiving erlotinib alone, no
      lung lesions were noted. In rats receiving BLM alone, diffuse alveolar damage
      (DAD) and, subsequently, pulmonary fibrosis of slight or moderate severity was
      observed. The administration of erlotinib to BLM-treated rats showed no
      exacerbation of lung injuries in indices such as macroscopic findings, lung
      weights, histopathological scores (lung lesion density and lung fibrosis score),
      and pulmonary hydroxyproline (HyP) level. These results suggest that erlotinib
      does not have any exacerbating effects on lung injuries induced by BLM in rats.

PMID- 20686338
TI  - A consecutive three alanine residue insertion mutant of human CAR: a novel CAR
      ligand screening system in HepG2 cells.
AB  - The expression of the CAR gene is lost in most cultured cell lines, and
      exogenously expressed CAR accumulates spontaneously in the nuclear compartment,
      where CAR is constitutively active. Therefore, the assessment of CAR-dependent
      transcriptional activation has to be evaluated using either animal models or
      primary cultured hepatocytes. Furthermore, due to the species-specific response
      of CAR to individual compounds, the results obtained with animal models are not
      directly applicable to human cases. We established a novel screening system for
      hCAR ligands (including agonists and inverse agonists) by expressing GAL4/DBD
      fused hCAR/LBD, in which three consecutive alanine residues were inserted between
      helix 11 and helix 12 of LBD, and a commercially obtained plasmid consisting of
      the firefly luciferase gene downstream of the GAL4 responsive element in a
      cultured cell line. Androstenol (Andro) and clotrimazole (CLT), which are both
      inverse agonists of hCAR, were classified as an antagonist and weak agonist,
      respectively, in our novel assay system. Among DDT and its metabolites DDE and
      DDD, only DDT worked as an agonist of the hCAR mutant, although all of them were
      enrolled as agonists of SXR. Using this system, the screening for hCAR ligands
      can be conducted without sacrificing animals.

PMID- 20686339
TI  - Effects of perfluorooctanoic acid (PFOA) exposure to pregnant mice on
      reproduction.
AB  - Perfluorooctanoic acid (PFOA) has similar characteristics to perfluorooctane
      sulfonate (PFOS) in reproduction toxicity featured by neonatal death. We found
      that PFOS exposure to mice during pregnancy led to intracranial blood vessel
      dilatation of fetuses accompanied by severe lung collapse which caused neonatal
      mortality. Thus, we adopted the corresponding experimental design to PFOS in
      order to characterize the neonatal death by PFOA. Pregnant ICR mice were given 1,
      5 and 10 mg/kg PFOA daily by gavage from gestational day (GD) 0 to 17 and 18 for
      prenatal and postnatal evaluations, respectively. Five to nine dams per group
      were sacrificed on GD 18 for prenatal evaluation; other 10 dams were left to give
      birth. No maternal death was observed. The liver weight increased dose
      dependently, with hepatocellular hypertrophy, necrosis, increased mitosis and
      mild calcification at 10 mg/kg. PFOA at 10 mg/kg increased serum enzyme
      activities (GGT, ALT, AST and ALP) with hypoproteinemia and hypolipidemia. PFOA
      treatment reduced the fetal body weight at 5 and 10 mg/kg. Teratological
      evaluation showed delayed ossification of the sternum and phalanges and delayed
      eruption of incisors at 10 mg/kg, but did not show intracranial blood vessel
      dilatation. Postnatal evaluation revealed that PFOA reduced the neonatal survival
      rate at 5 and 10 mg/kg. At 5 mg/kg pups were born alive and active and 16% died
      within 4 days observation, while all died within 6 hr after birth at 10 mg/kg
      without showing intracranial blood vessel dilatation. The cause of neonatal death
      by PFOA may be different from PFOS.

PMID- 20686340
TI  - Evaluation of liver and thyroid toxicity in Sprague-Dawley rats after exposure to
      polybrominated diphenyl ether BDE-209.
AB  - Our goal in the present study was to evaluate whether decabromodiphenyl ether
      (BDE-209), which is the most abundant polybrominated diphenyl ether (PBDE) found
      in human samples, affects against target organs. Sprague-Dawley male rats were
      exposed to vehicle or BDE-209 (100, 300, or 600 mg/kg body weight, daily) from
      postnatal day (PND) 10 to PND 42. There was no significant difference in body and
      male reproductive organ weight changes compared with controls. However, liver,
      thyroid and adrenal gland weights were significantly increased in the high-dose
      of BDE-209 group. BDE-209 significantly induced the expression of cytochrome P450
      (CYP1A2, CYP3A1, and CYP2B1) enzymes in the liver. Furthermore, constitutive
      androstane receptor (CAR) and pregnane xenobiotic receptor (PXR) expression
      levels were also increased in a dose-dependent manner. Total serum
      triiodothyronine (T3) concentration was significantly reduced in a dose-dependent
      manner, whereas the level of thyroid-stimulating hormone was significantly
      increased with BDE-209 treatment. In the histological findings, multiple areas of
      degenerated follicular epithelium and slight attenuation of the follicular
      epithelium were observed in the thyroid glands by high doses (300 and 600 mg/kg)
      of BDE-209 treatment. The presence of hepatocytic fatty degeneration and
      inflammatory foci were also observed in the 300 and 600 mg/kg of BDE-209 group.
      These findings demonstrate that BDE-209 induces hyperthyroidism and
      hepatotoxicity. In the future, further research is needed to determine the
      relationship between target organ toxicity and blood concentrations of BDE-209.

PMID- 20686341
TI  - Differential colon DNA damage induced by azo food additives between rats and
      mice.
AB  - Azo dyes, amaranth, allura red and new coccine, which are currently used as food
      color additives in Japan, have been reported to cause colon specific DNA damage
      in mice. To examine species difference in the DNA damage between rats and mice,
      each of dyes was administered to male mice (1 and 10 mg/kg) and male rats (10,
      100 and 1,000 mg/kg) by gavage. Brain, lung, liver, kidney, glandular stomach,
      colon, urinary bladder and bone marrow were sampled 3 hr (for mice) and 3, 6, 12
      and 24 hr (for rats) after the treatment. The alkaline comet assay showed DNA
      damage in the mouse colon 3 hr after the administration of all of the dyes at 10
      mg/kg. In rats, however, none of the dyes damaged DNA. Azo dyes should undergo
      metabolic reduction in the colon to be adducted to DNA. To determine transit time
      of the dyes to the colon after their administration, gastric emptying and
      intestinal transport in mice and rats were examined using brilliant blue FCF (BB)
      as an indicator. The half times of gastric emptying were 70 and 80 min for mice
      and rats, respectively; and about 60% of the BB was removed from the stomach 1 hr
      after the gastric intubation in both mice and rats. BB reached the mouse and rat
      colon 1 and 3 hr after the administration, respectively. Considering the wide
      dose range and sampling times well covering the transit time to the colon, rats
      may be insensitive to these azo dye-induced DNA damage.

PMID- 20686342
TI  - Mutagenicity of octane and tetrasodium pyrophosphate in bacterial reverse
      mutation (Ames) test.
AB  - We investigated the genotoxicities or mutagenicities of 2 chemicals (octane and
      tetrasodium pyrophosphate) with limited toxicological data in spite of their
      common usage based on Ames reverse mutation test. In this test, treatment of 2
      chemicals at each five dose did not induce mutagenicity in Salmonella typhimurium
      TA98, TA100, TA1535, TA1537, and in Escherichia coli WP2uvrA with and without
      metabolic activation. These results indicate that 2 chemicals do not have
      mutagenic potentials under the conditions examined in each study. Despite these
      results, it can affect by inducing inhalation, skin or eye contact, ingestion,
      and have affected central nervous system as a target organ. It is thus necessary
      to prepare the local exhaust system and personal protective equipments. Based on
      this study, we suggest that future studies should be directed toward chronic
      inhalation, carcinogenic test and so on.

PMID- 20686343
TI  - Distribution of 14C-2,3,7,8-tetrachlorodibenzo-p-dioxin to the brain and
      peripheral tissues of fetal rats and its comparison with adults.
AB  - Some forms of reproductive and developmental toxicity by 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) occur via initial damage to the pituitary
      synthesis of gonadotropins followed by the reduced expression of gonadal
      steroidogenic proteins. Defects in gonadotropin synthesis are highly specific to
      the periods from late fetal to early newborn stages. The reason for this
      specificity remains unknown. To address this issue, we compared the tissue
      distribution of 14C-TCDD between fetal and adult rats. In adult male rats, the
      major portion of TCDD given orally (approximately 33-42% dose) accumulated in the
      liver during day 1 and 5 after treatment. Very little TCDD (approximately 0.01%
      of the dose) distributed into the brain. A similar picture was also observed in
      TCDD-treated pregnant rats. The amount of TCDD transferred from a dam to the
      fetuses was extremely low (around 0.02% of the maternal dose/fetus) after 1 day
      of treatment. Male and female fetuses showed the same pattern in the brain
      distribution of TCDD. The rate of TCDD distribution to fetal brain, which was
      calculated on the basis of body burden to a fetus, was 100 times or more than
      that in adults. However, the brain content of TCDD (ng/g tissue) was comparable
      in fetuses and their dams, and adult males exposed to TCDD. These results suggest
      that although TCDD easily translocates to fetal brain, this is not a major
      mechanism for a fetal age-specific reduction in gonadotropin synthesis.

PMID- 20686344
TI  - 5-aminoimidazole-4-carboxamide-1-beta-ribofuranoside (AICAR) prevents nuclear
      translocation of constitutive androstane receptor by AMP-activated protein kinase
      (AMPK) independent manner.
AB  - The nuclear receptor superfamily consists of ligand-dependent transcription
      factors. Among them, constitutive androstane receptor (CAR) plays a key role in
      the detoxification of xenobiotics, inducing various drug-metabolizing enzymes
      including human CYP2B6 and its homologues of other species. AMP-activated protein
      kinase (AMPK) acts as an important energy sensor, being activated by an increased
      AMP/ATP ratio. CAR is activated by phenobarbital (PB) treatment. It has been
      recently reported that AMPK is involved in PB-mediated CYP2B induction both in
      vitro and in vivo. We investigated the relationship between the functions of AMPK
      and CAR in rat primary hepatocyte. The AMPK-activator 5-aminoimidazole-4
      Carboxamide-1-beta-Ribofuranoside (AICAR) unexpectedly repressed PB-induced CYP2B
      mRNA expression as well as AMPK-inhibitor compound C. In contrast, both the AMPK
      activator metformin and the constitutive active form of AMPK enhanced PB-induced
      PB-responsive enhancer module-driven reporter gene expression. We demonstrated
      that AICAR prevented nuclear translocation of CAR in an AMPK-independent manner
      in rat primary hepatocytes. AICAR might be a convenient probe for studying the
      mechanisms of PB-induced activation, especially nuclear translocation, of CAR in
      rat primary hepatocytes.

PMID- 20686345
TI  - Effect of imidacloprid on antioxidant enzymes and lipid peroxidation in female
      rats to derive its No Observed Effect Level (NOEL).
AB  - Technical imidacloprid was evaluated for its effect on oxidative stress and Lipid
      peroxidation (LPO) in female rats for No Observed Effect Level (NOEL). Activities
      of Superoxide dismutase (SOD), Catalase (CAT), Glutathione peroxidase (GPx), and
      level of Glutathione (GSH) and LPO were estimated in liver, kidney and brain of
      rats after oral administration of imidacloprid (5, 10, 20 mg/kg/day) for 90 days.
      Imidacloprid at 5 and 10 mg/kg/day has not produced changes in SOD, CAT, GPx and
      level of GSH and LPO in liver, brain and kidney. However 20 mg/kg/day has
      produced significant changes in SOD, CAT, GPx, GSH, LPO in liver; SOD, CAT and
      GPx in brain and LPO in kidney. Therefore, it is concluded that imidacloprid has
      not generated oxidative stress at 5 and 10mg/kg/day but induced changes at 20
      mg/kg/day. Hence 10 mg/kg/day may be considered as NOEL through antioxidant
      enzymes and LPO in female rats.

PMID- 20686346
TI  - Allyl isothiocyanate-induced changes in the distribution of white blood cells in
      rats.
AB  - The main pungent component of wasabi (Eutrema japonica) is known to be
      isothiocyanate and its derivatives, volatile substances. Allyl isothiocyanate
      (AITC) accounts for more than half of isothiocyanate derivatives. However, there
      is a little information on the effects of AITC on the immune system by analyzing
      the number of white blood cells (WBCs) over the course of days of AITC
      administration. In the present study, we studied the effects of AITC (dose=20
      mg/kg body weight/day for 10 days, subcutaneous: s.c.) on the number of WBCs
      (total WBCs, lymphocytes, monocyte, neutrophil, basophil and eosinophil) and
      plasma corticosterone concentrations in adult male rats. Administration of AITC
      decreased significantly the number of total WBCs on days 1-4 post s.c. injection
      by 25-27%. Administration of AITC also decreased the number of lymphocytes on
      days 1-10 by 21-36% and monocyte on days 1-8 by 28-78%. However, administration
      of AITC increased the number of neutrophil on days 8-10 by 61-112%. AITC did not
      change the number of eosinophil and basophil. Plasma corticosterone
      concentrations during the experimental period were 4.7-8.4 times significantly
      higher in the AITC group than in the control group, indicating that AITC induced
      stress-responses. The relative weights of thymus and adrenals per body weight
      were significantly lower and clearly higher in the AITC group than in the control
      group, respectively. These results suggest that AITC-mediated stress-responses
      are at least in part attributable to changes in the number of circulating WBCs.

PMID- 20686347
TI  - Evaluation of the potential biological toxicities of aqueous extracts from red
      tide phytoplankton cultures in in vitro and in vivo systems.
AB  - The biological toxic potentials of aqueous extracts from the dinophycean
      flagellates Gymnodinium impudicum and Alexandrium affine and the raphidophycean
      flagellate Chattonella ovata were examined in both in vitro and in vivo systems.
      Interestingly, the extract from A. affine was the only one that showed potent
      cytotoxicities towards HeLa, Vero, and Neuro-2a cells in a concentration
      dependent manner. Mice given intraperitoneal injections of the extracts revealed
      that none of the extracts exhibited serious toxicities in mice. However, temporal
      body weight loss was observed in the mice injected with the extract from A.
      affine during the early stage, and the dramatic enlargement of spleens was also
      observed in the mice on the 7th day after injection. Since A. affine extract
      showed potent hemolytic activity in vitro towards mouse erythrocytes, hemolytic
      anemia may be a possible mechanism responsible for the splenomegaly in the mice
      injected with A. affine extract. Similar marginal effects were observed in the
      mice injected with the extract from C. ovata; however, no significant toxic or
      detrimental effects were detected in the mice injected with the extract from G.
      impudicum. These results suggest that the extract from G. impudicum may not be
      contaminated with detectable levels of biologically hazardous compounds and may
      be relatively safe compared with the other two extracts.

PMID- 20686348
TI  - siRNA-mediated AMPKalpha1 subunit gene PRKAA1 silencing enhances methylmercury
      toxicity in HEK293 cells.
AB  - The environmental pollutant methylmercury is a potent neurotoxin. The mechanisms
      of toxicity and biological defense remain largely unknown. We found that
      inhibiting the expression of PRKAA1 (AMPKalpha1), an activated subunit of AMP
      activated protein kinase (AMPK), increased susceptibility of HEK293 cells to
      methylmercury toxicity. Treatment of the cells with AICAR (5-aminoimidazole-4
      carboxamide-1-beta-D-ribofuranoside), an AMPK activator, reduced the
      methylmercury toxicity. Here, we suggest for the first time that the activation
      (phosphorylation) of AMPK may play an important role in reducing the toxicity of
      methylmercury.

PMID- 20686349
TI  - Estrogenic effects of o,p'-DDT exposure in Japanese medaka (Oryzias latipes).
AB  - The persistent pesticide 1,1,1-trichloro-2-(2-chlorophenyl)-2-(4
      chlorophenyl)ethane (o,p'-DDT) has been implicated as an endocrine-disrupting
      chemical. In this study, we performed DNA microarray analysis to assess hepatic
      gene expression in male Japanese medaka (Oryzias latipes) exposed to 1 ppb and
      100 ppb o,p'-DDT for 48 hr. Results showed that 1 ppb o,p'-DDT induced the
      expression of choriogenins (chgH, chgL, and chgH minor), and 100 ppb induced the
      expression of vitellogenins (vtgI and vtgII) and estrogen receptor alpha. These
      genes showed considerably high up-regulation among the genes assayed and showed
      good dose-dependency. Thus, in this study the female hormone-like endocrine
      disrupting effect of o,p'-DDT at gene expression level was clearly observed in
      Japanese medaka.

PMID- 20686350
TI  - Distribution of astroglial lineage cells in developing chicken telencephalon from
      embryo to young chick.
AB  - The largest area of the avian telencephalon (Tc) is the subpallium [basal ganglia
      (BG)], and the pallium (cortex) is a narrow area located at the surface of the
      Tc. However, recent studies have proposed that most of the area of the avian Tc
      is the pallium, which corresponds to the cerebral cortex of mammals. This theory
      is based on neuronal elements with little regard to glial cells, which play
      important roles in neurogenesis. In the present study, we observed the
      distribution of glial cells using immunohistochemistry during maturation and
      discuss the division of the Tc by glial elements. In the early stage, the
      distribution and morphology of vimentin-positive radial glial cells were
      different between dorsal and ventral areas when they began to spread their
      processes toward the pia matter. During the development stage, vimentin-positive
      long processes divide the pallium and BG by the lamina pallio-subpallialis.
      Moreover, the pallium was divided into four regions by vimentin and glial
      fibrillary acidic protein-positive elements in the later stage.

PMID- 20686351
TI  - Comparison of parental behavior and offspring's anxiety behavior using a
      reciprocal F1 hybrid model.
AB  - Emotional behavior can be characterized by interactions between genes and
      environments, especially in the developmental period. However, in mice, the
      effects of paternal care on offspring's emotional development are not well
      understood even in cases in which the male mice show stable paternal care to the
      pups. In this study, we used a reciprocal hybrid model of C57BL/6 and BALB/c
      mice, which show different parental behaviors and emotional responses, and
      compared the emotional responses in pups in their adulthood by using the elevated
      plus-maze test. It was found that inbred male mice showed intensive parental
      behavior toward their pups, especially as parental contact behavior, and that the
      licking/grooming behavior of males was dependent on the strain of the female they
      were paired with. Also, BALB/c pairs showed less parental contact behavior than
      C57BL/6 pairs. In the elevated plus-maze test, BALB/c males and females showed
      higher anxiety behavior, and reciprocal hybrid offspring showed intermediate
      values between C57BL/6 and BALB/c mice. Although no significant difference was
      found in the parental care that offspring received and anxiety-related behavior
      between the two reciprocal hybrid strains, BALB/c pairs showed less parental
      contact behavior toward the pups as compared to C57BL/6 pairs, which would be
      associated with the higher anxiety-related behavior exhibited in the adulthood of
      BALB/c strain.

PMID- 20686352
TI  - Proteasome activity and biological properties of normal prion protein: a
      comparison between young and aged cattle.
AB  - Atypical bovine spongiform encephalopathy (atypical BSE) has recently been
      identified in several countries including Japan. Most cases of atypical BSE have
      been reported in cattle older than 8 years of age. To clarify the association
      between age and occurrence of atypical BSE, we investigated both the
      physiological properties and amount of cellular prion protein (PrP(C)) in brain
      homogenates from young and aged cattle by enzyme-linked immunosorbent assay and
      immunoblotting. The amount of PrP(C) in the brain homogenates was not
      significantly different between young and aged cattle, but the amount in the
      detergent-insoluble fraction in the aged cattle was significantly higher than
      that of young cattle. Significant differences were observed in neither of the
      glycosylation forms nor in proteinase K sensitivity in young and aged cattle. Age
      related changes included deposition of lipofuscin pigment and a decrease of 33%
      in proteasome activity in the brains of aged cattle compared to that of young
      cattle.

PMID- 20686353
TI  - An epidemiological survey of feline hemoplasma infection in Japan.
AB  - Hemoplasma (hemotropic mycoplasma) often causes hemolytic anemia in infected
      cats, especially those with immune suppression. An updated nationwide
      epidemiological survey of feline hemoplasmosis was conducted in Japan. Blood
      samples were collected from 1,770 outdoor-accessing cats from March to October
      2008. The infections were molecularly detected by PCR analyses, which are able to
      distinguish Mycoplasma haemofelis (Mhf), 'Candidatus M. haemominutum' (CMhm), and
      'Candidatus M. turicensis' (CMt) infections. Of the 1,770 cats, 468 cases (26.4%)
      revealed a single- or co-infection of feline hemoplasmas [Mhf alone, 42 cases
      (2.4%); CMhm alone, 280 cases (15.8%); CMt alone, 48 cases (2.7%); Mhf+CMhm, 28
      cases (1.6%); Mhf+CMt, 6 cases (0.3%); CMhm+CMt, 50 cases (2.8%); Mhf+CMhm+CMt,
      14 cases (0.8%)]. In addition, male gender, middle to old age, history of fight
      wounds, and feline immunodeficiency virus infection were shown to be risk factors
      for hemoplasma infection. Close attention must be paid to the acute onset of
      disease in feline practice because a prevalence of hemoplasma infection was
      detected even in clinically healthy cats.

PMID- 20686354
TI  - Small interfering RNA (siRNA) against the survivin gene increases apoptosis in a
      canine melanoma cell line.
AB  - The effect of down-regulation of survivin expression by small interfering RNA
      (siRNA) against the canine survivin gene on apoptosis was investigated by
      transfecting MCM-N1 (a canine malignant oral melanoma cell line) cells with siRNA
      using cationic liposomes. The siRNA against the canine survivin gene induced an
      increase in the rate of apoptotic cells and a decrease in the number of viable
      cells. We also measured sequence-specific down-regulation of survivin expression
      by reverse transcription-PCR and western blot analysis. The siRNA directed
      against survivin reduced both mRNA and protein expression in MCM-N1 cells. These
      findings suggest the importance of survivin in canine melanoma tumors for
      inducing apoptosis, and reinforce the possibility of using survivin as a putative
      therapeutic target in canine malignant melanoma tumor.

PMID- 20686356
TI  - ORF57: Master regulator of KSHV mRNA biogenesis.

PMID- 20686355
TI  - Structural basis of Ets1 cooperative binding to palindromic sequences on
      stromelysin-1 promoter DNA.
AB  - Ets1 is a member of the Ets family of transcription factors. Ets1 is
      autoinhibited and its activation requires heterodimerization with a partner
      protein or DNA-mediated homodimerization for cooperative DNA binding. In the
      latter case, Ets1 molecules bind to palindromic sequences in which two Ets
      binding sites (EBS) are separated by four base pairs, for example in the
      promoters of stromelysin-1 and p53. Interestingly, counteraction of
      autoinhibition requires the autoinhibitory region encoded by exon VII of the
      gene. The structural basis for the requirement of autoinhibitory sequences for
      Ets1 binding to palindromic EBS still remains unresolved. Here we report the
      crystal structure of two Ets1 molecules bound to an EBS palindrome of the
      stromelysin-1 promoter DNA, providing a plausible explanation for the requirement
      of exon VII-encoded sequences for Ets1 cooperative DNA binding. The proposed
      mechanism was verified both in vitro by surface plasmon resonance and in vivo by
      transcription-based assays.

PMID- 20686357
TI  - Genome-based vaccine development: a short cut for the future.
AB  - Bacterial infectious diseases remain a major cause of deaths and disabilities in
      the world. Although conventional vaccinology approaches were successful in
      conferring protection against several diseases, they failed in providing
      efficient vaccines against many others. Together to the sequencing of the first
      genome, a new chapter in the vaccinology history started to be written. Reverse
      vaccinology changed the way to think about vaccine development, using the
      information provided by the microorganisms' genome against themselves. Since
      then, reverse vaccinology has evolved and helped researchers to overcome the
      limits of the conventional vaccinology approaches and led to the discovery and
      development of novel vaccines concerning emerging diseases, like Neisseria
      meningitidis B and Streptococcus agalactiae. A lot of work must be done, but
      deciphering the information provided by genome sequences and using it to better
      understand the host-pathogen interactions has proved to be the key for
      protection.

PMID- 20686358
TI  - Genetic immunization: bacteria as DNA vaccine delivery vehicles.
AB  - The so-called DNA vaccination represents one of the most notable tools under
      development in the field of vaccinology. The concept of administering the gene
      coding for any given protective antigen and make responsible vaccinee's own cells
      to produce the protein appeals as too simple to be true. Indeed, the
      implementation of this approach for mass vaccination should overcome several
      bottlenecks, such as need of high dosages and poor immunogenicity. In this
      context, the use of live attenuated bacteria as delivery system for plasmid DNA
      has emerged as a promising alternative to overcome many of those pitfalls. In
      addition, this approach is not only amenable for mucosal administration, but
      allows to specifically target professional antigen presenting cells. This results
      in their transfection, as well as in their activation and maturation, due to
      their built-in adjuvant properties resulting from the stimulation of pattern
      recognition receptors. This chapter discusses the specific features that should
      be taken into consideration when designing a plasmid vector, current candidate
      bacterial carriers for DNA delivery and main safety issues.

PMID- 20686359
TI  - Involvement of p38alpha in the mitotic progression of p53(-/-) tetraploid cells.
AB  - The tumor suppressor protein p53 plays a major role in preserving genomic
      stability. p53 suppresses a pathway leading from normal diploidy to neoplastic
      aneuploidy (via an intermediate metastable stage of tetraploidy) at two levels:
      first by preventing the generation/survival of tetraploid cells, and second by
      repressing their aberrant multipolar division. Here, we report the
      characterization of p53(-/-) tetraploid cells, which-at difference with both
      their p53(-/-) diploid and their p53(+/+) tetraploid counterparts-manifest a
      marked hyperphosporylation of the mitogen-activated protein kinase MAPK14 (best
      known as p38alpha) that is particularly strong during mitosis. In p53(-/-)
      tetraploid cells, phosphorylated p38alpha accumulated at centrosomes during the
      metaphase and at midbodies during the telophase. Selective knockdown or
      pharmacological inhibition of p38alpha had a dramatic effect on p53(-/-) (but not
      p53(+/+)) tetraploids, causing the activation of the spindle assembly checkpoint,
      an arrest during the metaphase, a major increase in abnormal bipolar and
      monopolar mitoses, as well as an increment in the generation of multinuclear
      cells. We conclude that the mitotic progression of p53(-/-) (but not p53(+/+))
      tetraploids heavily relies on p38alpha, revealing a novel function for this
      protein in the context of aneuploidizing cell divisions.

PMID- 20686360
TI  - Translational research in bladder cancer: from molecular pathogenesis to useful
      tissue biomarkers.
AB  - Current risk stratification using clinical and pathological parameters in
      patients with urothelial carcinoma of the bladder (UCB) is insufficient.
      Additional information on the tumor biology can be derived from molecular
      biomarkers assessed in surgical UCB specimens and the predictive accuracy of
      oncologic end points may be improved. Biomarkers may also be used to predict the
      response to novel multimodal therapeutic approaches. Insights from the molecular
      pathogenesis of UCB can help identify potential biomarkers. A variety of
      candidate markers for future clinical use have been identified. However, results
      from comprehensive validation trials and prospective studies are still lacking.
      This precludes an application of molecular biomarkers in clinical practice at the
      moment. In this article, we review a selection of tissue biomarkers that are
      linked to important steps in molecular pathogenesis of UCB. We focused on
      biomarkers already tested in patient populations with potential clinical utility.

PMID- 20686361
TI  - CXCR4 signaling identifies a role for IFT2 in ER-negative breast cancers.

PMID- 20686362
TI  - Overexpression of EZH2 contributes to acquired cisplatin resistance in ovarian
      cancer cells in vitro and in vivo.
AB  - Enhancer of Zeste Homologue 2 (EZH2), a specific histone 3 lysine 27 (H3K27)
      methyltransferase, plays a critical role in tumorigenesis and cancer progression
      through epigenetic gene silencing and chromatin remodeling. However, the role of
      EZH2 in chemotherapy resistance is unknown. In this study, we found that EZH2 was
      overexpressed in cisplatin-resistant ovarian cancer cells compared with cisplatin
      sensitive cells. Knockdown of EZH2 by RNA interference (RNAi) resensitized drug
      resistant ovarian cancer A2780/DDP cells to cisplatin and decreased the level of
      H3K27 trimethylation (H3K27me3). Moreover, EZH2 downregulation suppressed cell
      proliferation and caused G2/M cell cycle arrest in A2780/DDP cells. Loss of EZH2
      also enhanced sensibility of tumor xenografts to cisplatin and inhibited tumor
      growth in vivo. Our results indicate that EZH2 is essential for chemotherapy
      resistance in cisplatin-resistant cancer cells in vitro and in vivo, which is
      probably through H3K27 methylation as well as regulation of cell proliferation.
      EZH2 could be a potential novel epigenetic target to overcome drug resistance.

PMID- 20686363
TI  - Blockade of FGF signaling: therapeutic promise for ovarian cancer.

PMID- 20686365
TI  - Where's the passion?
AB  - With this issue of CB&T, we introduce the first in an occasional series of
      articles on topics that impact our work or shape our professional lives. Our aim
      is to provide a platform for points of view that are both insightful and thought
      provoking. Have a perspective you'd like to share or an issue you'd like to
      discuss? We're open to any relevant topic. Send your 500-word article for
      Insider's Insight to Kim Mitchell (kmitchell @landesbioscience.com), publications
      director. Scientific research was once considered a pinnacle profession where
      intellectual rigor was paired with a passion for novel discovery. Today, despite
      better equipment, more funding and online access to a growing reservoir of data,
      researchers in some of the largest cancer research centers in the country appear
      to be spending less time in the lab and, perhaps, less time worrying about how
      their work impacts people with cancer. In his article, Dr. Kern asks whether
      research is evolving into a predictable career rather than a creative frontier
      and what that might portend.

PMID- 20686364
TI  - SILAC-based quantitative proteomic approach to identify potential biomarkers from
      the esophageal squamous cell carcinoma secretome.
AB  - The identification of secreted proteins that are differentially expressed between
      non-neoplastic and esophageal squamous cell carcinoma (ESCC) cells can provide
      potential biomarkers of ESCC. We used a SILAC-based quantitative proteomic
      approach to compare the secretome of ESCC cells with that of non-neoplastic
      esophageal squamous epithelial cells. Proteins were resolved by SDS-PAGE, and
      tandem mass spectrometry analysis (LC-MS/MS) of in-gel trypsin-digested peptides
      was carried out on a high-accuracy qTOF mass spectrometer. In total, we
      identified 441 proteins in the combined secretomes, including 120 proteins with >
      2-fold upregulation in the ESCC secretome vs. that of non-neoplastic esophageal
      squamous epithelial cells. In this study, several potential protein biomarkers
      previously known to be increased in ESCC including matrix metalloproteinase 1,
      transferrin receptor, and transforming growth factor beta-induced 68 kDa were
      identified as overexpressed in the ESCC-derived secretome. In addition, we
      identified several novel proteins that have not been previously reported to be
      associated with ESCC. Among the novel candidate proteins identified, protein
      disulfide isomerase family a member 3 (PDIA3), GDP dissociation inhibitor 2
      (GDI2), and lectin galactoside binding soluble 3 binding protein (LGALS3BP) were
      further validated by immunoblot analysis and immunohistochemical labeling using
      tissue microarrays. This tissue microarray analysis showed overexpression of
      protein disulfide isomerase family a member 3, GDP dissociation inhibitor 2, and
      lectin galactoside binding soluble 3 binding protein in 93%, 93% and 87% of 137
      ESCC cases, respectively. Hence, we conclude that these potential biomarkers are
      excellent candidates for further evaluation to test their role and efficacy in
      the early detection of ESCC.

PMID- 20686366
TI  - The role of MNK proteins and eIF4E phosphorylation in breast cancer cell
      proliferation and survival.
AB  - eIF4E is over-expressed in many tumours, including a high proportion of breast
      cancers. eIF4E is an oncogene, and signalling pathways which promote eIF4E
      activity represent potential targets for therapeutic intervention in cancer. MNKs
      phosphorylate eIF4E on serine 209, a modification that can be required for eIF4E
      dependent cell transformation. There is therefore a clear requirement to
      determine the role of MNKs in the proliferation and survival of cells from the
      major human tumours, such as breast cancer. Phosphorylated eIF4E protein was
      readily detectable in some breast tumour samples, but was below the limits of
      detection in others. Of 6 breast cancer cell lines representing the major sub
      types of breast cancer, phosphorylated eIF4E was readily detectable in 5 of them,
      with MCF-7 cells displaying markedly lower levels. Long term colony forming
      assays demonstrated that all the five lines with high levels of phosphorylated
      eIF4E were highly sensitive to a MNK inhibitor. In short term assays, a range of
      responses was revealed. MCF-7 cells were insensitive in both assays. The anti
      proliferative effects of the MNK inhibitor in breast cancer cells are primarily
      cytostatic, rather than cytotoxic, and are potentially due to the inhibition of
      cyclin D1 synthesis. Our data provide evidence that the sensitivity of breast
      cancer cells to MNK inhibition may correlate with baseline levels of eIF4E
      phosphorylation, and suggest that a proportion of breast cancers could be
      sensitive to inhibiting MNK kinase activity, and that the presence of
      phosphorylated eIF4E could provide a biomarker for the identification of
      responsive tumours.

PMID- 20686367
TI  - SU11248, a selective tyrosine kinases inhibitor suppresses breast tumor
      angiogenesis and growth via targeting both tumor vasculature and breast cancer
      cells.
AB  - SU11248 is a selective inhibitor of certain protein kinases including VEGFR types
      1-3 that are expressed in human breast cancer. The present study determines
      whether the anti-tumor activity of SU11248 results from the inhibition of
      angiogenesis, as well as direct anti-proliferation and anti-migration effects on
      breast tumors. Eight-wk old female mice (C57BL/6) were given SU11248 at 20-40
      mg/kg/d in drinking (distilled) water for 4 wks. Control mice received drinking
      water only. In the 2nd wk, 10(6) E0771 (mouse breast cancer) cells were injected
      in the left fourth mammary gland. Tumor size was monitored using dial calipers.
      At the end, tumors were isolated for measuring tumor size and intratumoral
      microvessel density (IMD) using CD31 immunohistochemistry. SU11248 significantly
      reduced tumor weight over the control (1.22 +/- 0.28 vs. 3.28 +/- 0.31 g; n = 8;
      p < 0.01) and IMD (111 +/- 10 vs. 155 +/- 6 IM#/mm2; p < 0.01). RT-PCR indicated
      that VEGFR1 and R2 were expressed in cultured E0771 cells. VEGF (10 ng/ml) caused
      a 42% increase in proliferation of E0771 cells, compared to the control (p <
      0.01; n = 8), and there was a significant decrease in proliferation of E0771
      cells treated with VEGF plus SU11248 (10 MUmol/L) vs. the control (65%, p <
      0.01). VEGF caused a 2-fold increase in the proliferation of HUVEC vs. the
      control (p < 0.01; n = 8), but its action was completely eradicated by SU11248.
      Neither VEGF nor SU11248 had any effect on the proliferation of cultured HAS MC.
      Migration assay showed that SU11248 (10 MUmol/L) significantly inhibited the
      migration of cultured E0771 cells. SU11248 significantly inhibited the
      proliferation of MCF-7 and MDAMB-231 cells in a dose-related manner. These
      findings support the hypothesis that the antitumor activity of SU11248 on breast
      cancer is possibly mediated by targeting the paracrine and autocrine effects of
      VEGF on breast cancer to suppress tumor angiogenesis, proliferation and
      migration.

PMID- 20686368
TI  - Cervical, uterine corpus, and ovarian cancer mortality in Greece during 1980 to
      2005: a trend analysis.
AB  - INTRODUCTION: The aim of the present study was to analyze cervical, uterine
      corpus, and ovarian cancer mortality, between 1980 and 2005, in Greece. METHODS:
      Mortality data and population age distribution were provided by the National
      Statistical Service of Greece. Time trends of mortality were calculated for each
      tumor type per 100,000 women in the whole female population of Greece, and 2
      different age groups, that is, women aged 49 years and younger and those 50 years
      and older. Joinpoint regression was used for further analysis of mortality
      trends. RESULTS: Overall, cervical and uterine corpus cancer mortality in the
      whole female population of Greece had a slightly decreasing trend between 1980
      and 2005, whereas ovarian cancer mortality rates increased steadily throughout
      the period studied. Subgroup analyses according to age showed that cervical
      cancer mortality decreased very slightly only in women older than 50 years,
      whereas it remained steady in younger women. Uterine corpus cancer mortality
      decreased slightly in both age groups, but increased during the last years of the
      study period in the older age group. Ovarian cancer mortality increased in women
      older than 50 years, whereas it remained steady in the younger age group.
      Joinpoint regression analysis showed that only the increase after 1997 in the
      mortality trend for uterine corpus cancer in women 50 years and older was
      statistically significant (P = 0.0044). CONCLUSIONS: Although our findings
      regarding cervical cancer mortality in Greece are encouraging, still more efforts
      are needed, particularly in preventing cervical cancer in younger women. The
      increasing trend of uterine corpus and ovarian cancer mortality in older women
      suggests that development of well-organized tertiary centers for the
      implementation of modern therapeutic modalities is urgently needed.

PMID- 20686369
TI  - The British Gynaecological Cancer Society Delphi consultation exercise on
      expected standards of practice for doctors specializing in the area of
      gynecological oncology.
AB  - OBJECTIVE: To determine a set of auditable standards applicable to physicians
      working in the area of gynecological oncology, which could be implemented as
      accreditation criteria for the revalidation procedure. DESIGN: A 3-round Delphi
      consultation exercise. SETTING: British Gynaecological Cancer Society (BGCS)
      members and delegates at the 2006 and 2007 Annual BGCS conferences Population 35
      BGCS members, 72 delegates attending the 2006 BGCS conference and 120 delegates
      attending the 2007 conference. METHODS: A preliminary Delphi consultation of
      members was performed electronically to determine the contents of the final
      Delphi questionnaires. Prioritization was achieved by scoring each parameter on a
      5-point Likert scale. MAIN OUTCOME MEASURE: The mean score awarded to each
      benchmarking parameter and the identification of parameters scoring 4 or above
      75% or more of the respondents. RESULTS: The first round contained responses from
      68 participants in stage 1 and 72 in stage 2. The second round included 120
      participants. Nine of the auditable standards in first round and 10 in the second
      round achieved a score of 4 or above 75% or more of the participants and were
      therefore considered to be essential for revalidation. The selected criteria
      focused on an individual clinician's caseload and performance, multidisciplinary
      team working and continued professional development. CONCLUSIONS: This study has
      used the Delphi technique to identify auditable standards which could be used in
      the revalidation process of physicians working in the area of gynecological
      cancer.

PMID- 20686370
TI  - Alternative splicing-related factor YT521: an independent prognostic factor in
      endometrial cancer.
AB  - BACKGROUND: YT521 is a splicing factor involved in alternative splicing
      regulation of several tumor biological important genes. Two messenger RNA (mRNA)
      isoforms due to YT521 exon6 alternative splicing exist, with so far unknown
      functional consequences. Further evidence exists for a direct influence of YT521
      expression in tumorigenesis because its mRNA level is changed in tumors compared
      with physiological tissue. We investigated the potential impact of YT521
      expression on tumor biological parameters in endometrial cancer (EC). METHODS:
      Real-time reverse transcription-polymerase chain reaction specifically detecting
      YT521 exon6-retention and exon6-skipping mRNA isoforms and immunohistochemistry
      were performed in a cohort of 130 EC tissue samples. RESULTS: Whereas YT521 exon6
      retention mRNA was detectable in 86 (66.2%), the exon6-skipping isoform mRNA was
      expressed in only 8 (6.2%) of all EC samples. On the protein level, 104 (80%) of
      EC samples showed nuclear expression. The mRNA levels of exon6-skipping isoform
      were not correlated to any of the clinicopathological parameters of EC. In
      contrast, YT521 exon6-retention mRNA expression was positively correlated to
      metastasis (R = 0.196, P = 0.026) and inversely correlated to the protein
      expression levels (R = -0.205, P = 0.019). In univariate analyses, higher levels
      of YT521 exon6-retention mRNA were correlated to a poorer progression-free
      survival (P = 0.003), and this is confirmed by multivariate analyses (P = 0.019).
      The negative YT521 protein expression was correlated to poorer overall and
      disease-specific survival (P = 0.036 and P = 0.034), respectively, in univariate
      analyses. They are also confirmed by multivariate analyses (P = 0.021 and P =
      0.010, respectively). CONCLUSIONS: We characterized for the first time in a
      clinical setting a new but rare exon6-skipping mRNA splicing isoform of YT521.
      Furthermore, we identified YT521 as a potential new independent prognostic factor
      for patients with EC: the lack of YT521 protein in tumor cells was highly
      predictive for a poor overall and disease-specific survival and independent from
      the histological subtypes.

PMID- 20686371
TI  - Systematic lymphadenectomy for survival in epithelial ovarian cancer: a meta
      analysis.
AB  - BACKGROUND: The role of systematic lymphadenectomy (SL) remains unclear for
      improving overall survival (OS) in epithelial ovarian cancer (EOC). To evaluate
      the role of SL in EOC, we performed a meta-analysis for comparing the efficacy
      for OS between SL and unsystematic lymphadenectomy (USL). METHODS: After the
      extensive literature search between January 1995 and December 2008, we analyzed 9
      studies (2 randomized controlled trials [RCTs] and 7 observational studies) with
      21,919 patients with EOC who underwent staging laparotomy including SL or USL.
      RESULTS: Although SL was a favorable factor for OS compared with USL (hazard
      ratio [HR], 0.72; 95% confidence interval [CI], 0.68-0.76), the efficacy of SL on
      increased OS could not be determined in all-stage and early-stage EOC owing to
      the lack of RCTs and the deviation of weight by large-scale observational
      studies, whereas SL improved OS in advanced-stage EOC (HR, 0.70; 95% CI, 0.67
      0.75). Moreover, SL increased OS in patients with all-stage disease who underwent
      optimal debulking surgery (HR, 0.84; 95% CI, 0.69-0.99), whereas it could not
      improve OS statistically in early-stage and advanced-stage diseases. However, SL
      showed increased OS with marginal significance in advanced-stage EOC patients
      treated with optimal debulking surgery (HR, 0.82; 95% CI, 0.66-1.02).
      CONCLUSIONS: These findings suggest the possibility that SL can improve OS in
      advanced-stage EOC. However, the efficacy of SL on OS is still unknown because of
      the lack of RCTs, which requires more relevant studies for investigating the role
      of SL in EOC.

PMID- 20686372
TI  - Kallikrein-related peptidase 10 (KLK10) expression and single nucleotide
      polymorphisms in ovarian cancer survival.
AB  - INTRODUCTION: Kallikrein-related peptidase 10 (KLK10) overexpression is a
      predictor of poor disease outcome in women with late-stage ovarian cancer. We
      aimed to identify whether KLK10 overexpression could be attributed to genetic
      variants, in particular, in hormone response elements or transcription factor
      binding sites. METHODS: Cox regression analysis was used to assess the
      association between 2 tag and 1 exonic KLK10 single nucleotide polymorphisms
      (SNPs) and the survival of 319 patients with ovarian cancer. Four different
      ovarian cancer cell lines were investigated for KLK10 expression after hormone
      stimulation, and sequence variation in the 3.6-Kb upstream of the KLK10 start
      site. In silico analyses of SNPs in cell lines and from published databases were
      undertaken to identify further research novel and potentially functional SNPs
      that are not covered by tag SNPs. RESULTS: The KLK10 SNPs investigated were not
      associated with ovarian cancer survival. However, steroid hormone treatment of
      ovarian cell lines showed KLK10 up-regulation in response to estrogen and
      estrogen plus progesterone treatments in the aggressive cell line PEO1 and
      affirmed a role for KLK10 in aggressive ovarian cancer. Potentially functional
      KLK10 SNPs were identified by cell line sequencing and bioinformatic analysis.
      CONCLUSION: Potentially functional candidate KLK10 SNPs require investigation in
      future association studies of ovarian cancer risk and survival, including
      rs3760738 identified in aggressive ovarian cancer cell lines and predicted to
      affect transcription factor binding sites.

PMID- 20686373
TI  - The role of diaphragmatic surgery during interval debulking after neoadjuvant
      chemotherapy: an analysis of 74 patients with advanced epithelial ovarian cancer.
AB  - OBJECTIVES: The purpose of this retrospective study was to evaluate diaphragmatic
      surgery in achieving optimal cytoreductive results and its associated
      complications during interval debulking surgery in patients with advanced ovarian
      cancer. METHODS: After retrospective review of medical records, diaphragmatic
      surgery was performed in 74 of 128 consecutive patients with advanced epithelial
      ovarian cancer who underwent interval debulking, between September 1993 and
      December 2007. Four different approaches were performed: coagulation (group 1),
      stripping (group 2), combination of stripping with coagulation (group 3), and
      diaphragm full-thickness resection including muscle with pleura (group 4).
      Cytoreductive outcome, morbidity, overall survival, and disease-free survival
      were analyzed. RESULTS: Two patients (2.7%) had International Federation of
      Gynecology and Obstetrics stage IIIB disease; 46 (62.16%), stage IIIC; and 26
      (35.13%), stage IV. After 3 to 4 cycles of neoadjuvant platinum-based
      chemotherapy, the diaphragmatic disease was coagulated in 43 patients (58.10%)
      and was only stripped in 10 (13.51%); in 19 patients (25.67%), a combination of
      these techniques was applied; and in 2 (2.70%), the disease was resected, with
      the adjacent infiltrated part of the diaphragmatic muscle and the pleura above
      it. Debulking to no residual was achieved in 95%, 100%, 100%, and 50% for groups
      1, 2, 3, and 4, respectively. The median disease-free survival was 15, 14, and 14
      months, and the median overall survival was 34, 30, and 51 months for groups 1,
      2, and 3, respectively, and were not reached for group 4. Minor and major
      complications were comparable among the groups. Pleural effusions were the most
      frequent associated complication, and chest tube placement (1.3%) or
      thoracocentesis (4%) were necessary for the relief of respiratory distress. The
      perioperative mortality rate was 0%. CONCLUSIONS: Diaphragmatic surgery during
      interval debulking enhances optimal cytoreduction rates and improves survival
      with acceptable and manageable morbidity. In patients with thick (>4 mm) or large
      (>1 cm) lesions, stripping the diaphragm or full-thickness resection of the
      diaphragmatic muscle is preferred.

PMID- 20686374
TI  - Survival and disease relapse in surgical stage I endometrioid adenocarcinoma of
      the uterus after adjuvant vaginal vault brachytherapy.
AB  - INTRODUCTION: Advanced age, deep myoinvasion, whole cavity or lower uterine
      segment tumors, poor differentiation, and lymphovascular space invasion are known
      to increase recurrence risk and adversely affect survival in stage I endometrioid
      adenocarcinoma of the uterus. OBJECTIVES: To ascertain survival rates, failure
      patterns, and salvageability and to correlate adverse histopathologic effects to
      recurrences in these patients. METHODS: Data of 162 patients with surgical stage
      I endometrioid adenocarcinoma of the uterus with an increased risk of recurrence
      were reviewed from the year 1997 to 2008 at KK Gynaecological Cancer Centre,
      Singapore. Each patient underwent surgical staging and histopathologic evaluation
      and received high-dose rate vaginal vault brachytherapy. The data of all patients
      were discussed in a multidisciplinary meeting. RESULTS: The mean patient age was
      58.9 years. Most patients (54.3%) had surgical stage IC endometrioid
      adenocarcinoma, whereas the rest had stage IB. Grade 2 tumors were seen in 53.7%
      of the patients and grade 3 in 21.61%. The mean follow-up duration was 52.9
      months, with a maximum of 11.5 years. Five- and 10-year survival rates were 94%
      and 89%, respectively. There were 9 recurrences (5.56%). Stage IC had 77.78%
      recurrences, whereas stage IB had 22.22%, the median time being 19 months. The
      initial 3 years had 77.78% relapses. There was no recurrence in grade 3 tumors,
      with a 100% 5-year survival rate for stage IC grade 3. Age, lymphovascular space
      invasion, and tumor volume and location were not significant parameters in
      surgical stage I endometrioid adenocarcinoma patients who failed. One patient had
      isolated pelvic failure, whereas 5 had a pure distant relapse. Three patients
      failed at both locoregional and distant sites. Vault recurrence coupled with
      distant metastasis occurred in 1 patient. Three patients (33.33%) with
      recurrences, all with limited relapse sites, were salvaged, with a mean survival
      of 71.33 months. The median survival for recurrent endometrial cancer was 5
      years. CONCLUSIONS: This treatment has excellent survival rates with acceptable
      morbidity, and recurrence is mostly distant.

PMID- 20686375
TI  - Laparoscopically assisted vaginal hysterectomy (LAVH) versus total abdominal
      hysterectomy (TAH) in endometrial carcinoma: prospective cohort study.
AB  - OBJECTIVE: To determine the feasibility and safety of laparoscopically assisted
      vaginal hysterectomy in the treatment of presumed stage I endometrial cancer.
      STUDY DESIGN: This was a prospective cohort study without randomization of 182
      consecutive patients who underwent surgery for early endometrial cancer or
      atypical hyperplasia at the West Kent Gynaecological Oncology Centre, UK. Seventy
      four had laparoscopically assisted vaginal hysterectomy and bilateral salpingo
      oophorectomy (BSO), and 108 had a total abdominal hysterectomy and bilateral
      salpingo-oophorectomy. Lymphadenectomy was performed in 153 patients, and lymph
      node sampling was performed in 2 patients. Twenty-seven patients with serous
      papillary endometrial cancer in addition had an omentectomy. The groups were
      compared for epidemiological and clinical characteristics, surgical outcomes,
      hospital stay, lymph node harvest, and intraoperative and postoperative
      complications. RESULTS: The patients in the laparoscopy group had less blood
      loss, similar number of lymph nodes removed, less need for analgesia, and shorter
      hospital stay but longer operative time than those treated by laparotomy. In our
      study, we had 4 conversions (5.4%) from laparoscopy to laparotomy. Twenty-eight
      (41%) patients who had laparoscopic surgery were obese (body mass index [BMI] >30
      kg/m2). Postoperative complications were more common in the laparotomy group
      (34%) than in the laparoscopy group (6%). No major complications occurred in the
      laparoscopy group. Wound infection was the most common complication in laparotomy
      patients, and this invariably happened to obese patients (BMI >30 kg/m2). There
      were 6 readmissions, all from the laparotomy group. CONCLUSIONS: Laparoscopic
      surgery is a safe and reliable alternative to open surgery in the management of
      early endometrial cancer patients, with significantly reduced hospital stay and
      complications, especially in those patients with an elevated BMI.

PMID- 20686376
TI  - Selected immunohistochemical prognostic factors in endometrial cancer.
AB  - OBJECTIVE: The objectives of this study were to assess the immunohistochemical
      expression of p53, bcl-2, c-erbB-2, Ki-67, estrogen (ER) and progesterone (PR)
      receptors, matrix metalloproteinase-7 and -26 (MMP-7 and MMP-26) in endometrial
      cancer patients and to assess the relation between steroid receptor positivity
      and other markers. DESIGN: Experimental prospective study. SETTING: Department of
      Obstetrics and Gynecology, Department of Genetics, Department of Pathology,
      Palacky University Medical School and University Hospital Olomouc. METHODS: We
      studied 144 cases of primary untreated endometrial carcinoma in which the p53,
      bcl-2, c-erbB-2, Ki-67, ER, PR, MMP-7, and MMP-26 antigens were investigated with
      the use of immunohistochemical methods. We evaluated the correlations among
      immunohistochemical staining and the age, International Federation of Gynecology
      and Obstetrics stage, grading, depth of invasion, and metastatic spread to lymph
      nodes. RESULTS: Mean age was 65.7 years (range, 34-90 years). p53, bcl-2, c-erbB
      2, Ki-67, ER, and PR were positive in 35 (24.3%), 100 (69.4%), 41 (28.4%), 65
      (45.1%), 115 (79.8%), and 127 (88.1%) cases, respectively. Matrix
      metalloproteinases were evaluated in a group of 70 patients, wherein MMP-7 was
      positive in 33 patients (47.1%) and MMP-26 was positive in 40 patients (57.1%).
      The expression of MMP-7 decreased with higher patient age. p53 and Ki-67
      overexpression was found to be related to poor differentiation. Immunostaining
      for bcl-2 correlated with the positivity of steroid receptors status, whereas
      immunostaining for c-erbB-2 correlated inversely with ER-positive group of cases.
      CONCLUSIONS: The overexpression of p53 and Ki-67 seems to indicate a more
      malignant phenotype, whereas bcl-2 expression in dependence of steroid receptor
      positivity could contribute to the identification of high-risk tumors.

PMID- 20686377
TI  - Contribution of ultrasonography to endometrial cancer screening in patients with
      hereditary nonpolyposis colorectal cancer/Lynch syndrome.
AB  - OBJECTIVES: Screening for endometrial cancer is recommended in women at risk for
      hereditary nonpolyposis colorectal cancer/Lynch syndrome. No screening tool has
      been validated. The objective of this study was to assess the performance of
      ultrasonography used to screen for atypical hyperplasia and cancer in women at
      risk for hereditary nonpolyposis colorectal cancer/Lynch syndrome. Endometrial
      biopsy was the reference standard. MATERIALS AND METHODS: Of 85 women with
      mismatch repair gene mutations or Amsterdam II criteria who were studied
      prospectively at our institution, 58 had 96 paired ultrasound-biopsy evaluations
      and were included in the study. Transvaginal or transabdominal ultrasonographic
      finding was considered normal if no polyps or intrauterine abnormalities were
      seen and if the maximum endometrial thickness was less than 4 mm in
      postmenopausal women not receiving hormonal replacement therapy or less than 6 mm
      in other women. Endometrial biopsy results were categorized as not interpretable,
      normal, or showing atypical hyperplasia or cancer. Sensitivity, specificity,
      positive predictive value, negative predictive value, and likelihood ratio of
      ultrasonography were computed. RESULTS: The 58 patients had a mean age of 42.5
      years and a median follow-up duration of 51.4 months (range, 17-106 months; 246
      patient exposure years). Cancer was diagnosed in 2 patients. Ultrasonography had
      100% sensitivity and 100% negative predictive value, 2.2 positive likelihood
      ratio, and 0 negative likelihood ratio. No interval cancers occurred.
      CONCLUSIONS: Ultrasonography had high sensitivity and an excellent negative
      likelihood ratio in this study. Further studies are needed, and ultrasonography
      should be compared with clinical follow-up, diagnostic hysteroscopy, or
      endometrial biopsy alone.

PMID- 20686378
TI  - Clinical significance of serum CA-125 and soluble tumor necrosis factor receptor
      type I in cervical adenocarcinoma patients.
AB  - HYPOTHESIS: The purpose of this study was to answer the question whether the
      measurement of the pretreatment tumor markers and cytokine levels would be of
      clinical use in patients with cervical adenocarcinoma. METHODS: CA-125,
      carcinoembryonic antigen (CEA), and squamous cell carcinoma (SCC), as well as
      interleukin 6 (IL-6), IL-8, vascular endothelial growth factor, IL-1 receptor
      antagonist, soluble tumor necrosis factor receptor type I (sTNF RI), and sTNF
      RII, were assessed in the sera of 120 cervical adenocarcinoma patients. RESULTS:
      CA-125 presented a better diagnostic sensitivity than did CEA and SCC, whereas
      the concentration of most cytokines, except for sTNF RII, revealed higher
      sensitivity, than did the standard tumor markers. The highest sensitivity was
      found for sTNF RI. The concentrations of the examined parameters were found to be
      significantly higher in patients with advanced stage (IIB-IV) as compared with
      patients with I-IIA stage. [Float1]Serum concentration of IL-6 was the only one
      that differs significantly, depending on the histological grade. During the 3
      year follow-up, 25 patients relapsed, and 73 patients were disease-free.
      Significantly higher pretreatment serum concentrations of the examined parameters
      (except for SCC and IL-1 receptor antagonist) were found in patients who
      developed recurrences. Soluble tumor necrosis factor receptor type I and CA-125
      were found to present the highest sensitivity, with areas under the receiver
      operating characteristic curve of 0.833 and 0.809, respectively. As the result of
      univariate analysis, CA-125, CEA, sTNF RII, IL-6, sTNF RI, and clinical stage
      were considered factors of poor prognosis. Multivariate analysis has proven that
      CA-125 and clinical stage were the only significant independent prognostic
      factors of the disease-free survival. CONCLUSION: CA-125 is an independent
      prognostic factor for disease-free survival. Our results have also demonstrated
      that sTNF RI is probably the most useful marker in cervical adenocarcinoma
      patients, especially in the early stages of disease.

PMID- 20686379
TI  - Impact of different sectioning of excision biopsies of the cervical
      transformation zone for detection of invasive cervical cancer in 2 European
      centers related to national cervical screening programs.
AB  - BACKGROUND: The impact of the number of sections used in cervical excision
      biopsies of transformation zone on sensitivity of histological detection of
      cervical cancer is poorly documented. AIM: To assess whether different techniques
      of sectioning cervical excision biopsies in 2 European laboratories influence the
      finding of cervical cancer by histopathological examination. MATERIALS AND
      METHODS: The routine assessment at the Department of Histopathology and Cytology,
      Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK (Sheffield),
      encompassed sectioning a cone in 3-mm tissue blocks and cutting 3 levels per
      block. At the Institute of Pathology, Faculty of Medicine, University of
      Ljubljana, Slovenia (Ljubljana), cones were cut in a 3- to 4-mm-thick tissue
      block, and 10 levels were cut per block, spaced every 100 microm. The number of
      blocks and levels per block were assessed for each cone. Histopathological
      detection of cervical carcinoma between the laboratories was compared. RESULTS:
      Among 820 cones in the Sheffield laboratory, we detected 35 invasive carcinomas,
      whereas 6 invasive carcinomas were detected among 94 cones in the Ljubljana
      laboratory. Although the Slovenian laboratory examined a significantly larger
      number of levels per cone biopsy (64 vs 24 in Sheffield), this was not associated
      with a larger proportion of invasive cervical carcinoma, especially foci of stage
      IA1 or high-grade cervical intraepithelial neoplasia diagnosed on excision
      biopsies: 6.4% of invasive cervical carcinomas (5 [83.3%] of stage IA1) in
      Ljubljana and 4.3% (30 [85.7%] of stage IA1) in Sheffield laboratory (P > 0.05);
      71.2% of high-grade cervical intraepithelial neoplasia in Ljubljana and 75.5% in
      Sheffield (P > 0.05). CONCLUSIONS: Our assessment showed that a method with a
      large number of levels per cervical cone or large loop excision of the
      transformation zone biopsy did not increase sensitivity for the detection of
      cervical cancer. However, extensive sectioning substantially affects the
      pathologist's workload, and this may need to be reconsidered.

PMID- 20686380
TI  - Digital colposcopy for the diagnosis of cervical adenocarcinoma using a narrow
      band imaging system.
AB  - INTRODUCTION: Although the colposcopic features of cervical glandular disease and
      cervical adenocarcinoma are not widely well known, unique microvascular patterns
      are reportedly useful for identifying such diseases. The narrow band imaging
      (NBI) system used in endoscopy can be used to obtain high-contrast vascular
      images. Therefore, we examined the utility of NBI colposcopy and compared the
      results with those of conventional colposcopy. METHODS: Twenty-one patients with
      adenocarcinoma in situ or early invasive adenocarcinomas were examined using
      digital NBI colposcopy, and the photo records were compared with those of
      conventional colposcopy. The histological examination and immunohistochemistry
      with anti-CD31 antibody confirmed the microvascular pattern. RESULTS: Digital NBI
      colposcopy depicted the fine vascular texture on the surface of the cervix more
      clearly than conventional colposcopy. The vascular pattern was depicted in 86%
      (18/21) of glandular disease cases. The characteristic fine vascular patterns
      were critical for identifying cervical glandular diseases. CONCLUSIONS: Digital
      NBI colposcopy was useful for identifying early cervical adenocarcinoma as well
      as adenocarcinoma in situ. This system yields cervical glandular disease-related
      colposcopic findings that may be useful for both clinical and educational
      purposes.

PMID- 20686381
TI  - Neoadjuvant weekly carboplatin and paclitaxel followed by radical hysterectomy
      for locally advanced cervical cancer: long-term results.
AB  - INTRODUCTION: To determine the long-term effect of neoadjuvant chemotherapy with
      paclitaxel and carboplatin on a weekly schedule followed by radical surgery for
      patients with locally advanced cervical cancer. MATERIALS AND METHODS: Thirty
      patients with stage IB2 to IIIB uterine cervical cancer were treated with
      paclitaxel (60 mg/m) and carboplatin (area under the curve, 2-an area under the
      time-concentration curve of 2 mg x min/mL based on creatinine clearance) every
      week for 6 cycles. A radical hysterectomy was performed 6 days after the final
      administration of neoadjuvant chemotherapy. The patients were followed up, and 5
      year progression-free survival (PFS) and overall survival (OS) were evaluated.
      RESULTS: Of 30 patients, 28 were followed up. The median follow-up period was
      55.6 months (range, 26-83 months). An objective response (complete response +
      partial response) to the treatment was observed in 26 patients (87%; 95%
      confidence interval, 70%-95%). Two had complete response, 4 had stable disease,
      and the remaining patients had partial response; progressive disease was not seen
      in this study. A radical hysterectomy was performed in 28 patients without delay.
      Thirteen patients with high-risk factors received radiotherapy after surgery. The
      5-year PFS and OS rates were 78.6% and 81.8%, respectively. The 5-year PFS and OS
      for patients with stage IB2 to IIB cervical cancer were 79.2% and 83.1%,
      respectively, which were comparable with those in the concurrent chemoradiation
      therapy study previously reported. There was no significant correlation in
      survival between preoperative staging and cell type, whereas larger initial tumor
      size and lymph node metastasis tended to be negatively correlated with survival.
      CONCLUSIONS: Neoadjuvant chemotherapy with paclitaxel and carboplatin on a weekly
      schedule followed by radical surgery for patients with locally advanced cervical
      cancer is a promising mode of therapy that may improve the prognosis. It would be
      worthwhile to conduct larger-scale trials for comparison with the results of the
      chemoradiation therapy study.

PMID- 20686383
TI  - Cyclooxygenase-2 gene polymorphisms and risk of cervical cancer in a North Indian
      population.
AB  - INTRODUCTION: Single nucleotide polymorphisms in the cyclooxygenase-2 (COX-2)
      might contribute to differential COX-2 expression and subsequent interindividual
      variability in susceptibility to cancer. This study sought to evaluate the
      effects of COX-2 +8473T/C (rs5275) and -765G/C (rs20417) gene polymorphisms on
      the risk of cervical cancer in women of Northern India. METHODS: Peripheral blood
      samples were collected from 200 histopathologically confirmed patients with
      cervical cancer and 200 unrelated, healthy female controls of similar ethnicity.
      Questionnaire survey was conducted to comprehend the demographic data, smoking
      status, and cancer stage of patients. Polymerase chain reaction-based restriction
      fragment length polymorphism was used to detect the genotypes of the COX-2 gene.
      RESULTS: Cyclooxygenase-2 +8473CC genotype was associated with a significantly
      reduced risk of cervical cancer (P = 0.036; odds ratio, 0.4; 95% confidence
      interval, 0.1-0.9), whereas COX-2 -765G/C polymorphism demonstrated no
      association. In addition, no significant association with clinical stages of
      cervical cancer and modulation of risk due to tobacco usage was observed in our
      study. CONCLUSIONS: Cyclooxygenase-2 +8473T/C gene polymorphism demonstrated
      protective effect in North Indian women. Further studies evaluating the role of
      COX-2 gene polymorphisms in ethnically diverse populations and a larger cohort
      may help in understanding the etiopathogenesis of cervical cancer in women
      worldwide.

PMID- 20686382
TI  - Green tea compound in chemoprevention of cervical cancer.
AB  - OBJECTIVES: Human papillomavirus (HPV) infection is closely associated with the
      development of more than 95% of cervical cancer. Clinical trials using several
      chemopreventive agents are underway, but results are inconclusive. Most agents
      used in trials inhibited the growth of cancer cells in vitro, and about half of
      patients had some degree of clinical responses; however, the therapeutic effect
      was confounded by high rates of spontaneous regression and relapse. The selection
      of nontoxic agents especially food, beverage, and natural products that suppress
      oncogenic HPV, inhibit malignant transformation, and can additionally be used
      long term may be important for cervical cancer prevention. METHODS: We evaluated
      green tea compound (epigallocatechin gallate and polyphenols E) effects on
      immortalized cervical epithelial and cervical cancer cells. HPV-immortalized
      cervical epithelial cells, TCL1, and HPV-positive cervical cancer cells, Me180
      and HeLa, were used in the study. The effects of green tea compounds on cell
      growth, apoptosis, cell cycle, and gene expression were examined and
      characterized. RESULTS: Both epigallocatechin gallate and polyphenols E inhibited
      immortalized cervical epithelial and cancer cell growth. Apoptosis induction and
      cell cycle changes were observed in a dose-dependent manner. Western blot
      analysis of apoptosis-related proteins, p53 and p21, showed dose-dependent
      increase, whereas p27 was not affected. HPV-E7 protein expression was decreased
      by green tea compounds. CONCLUSIONS: This study provides information on the
      potential mechanisms of action of green tea compounds in suppression of HPV
      related cervical cells, and it will enable us to assess the feasibility of using
      these agents.

PMID- 20686384
TI  - Detection of human telomerase RNA gene in cervical cancer and precancerous
      lesions: comparison with cytological and human papillomavirus DNA test findings.
AB  - OBJECTIVES: The aims of this study were to compare the findings of fluorescence
      in situ hybridization (FISH) detection of human telomerase RNA gene (hTERC)
      amplification with that of cytological and human papillomavirus (HPV) DNA tests
      and explore the possibility to improve the accuracy of the diagnoses of high
      grade cervical intraepithelial neoplasia (CIN) and cervical cancer. METHODS: A
      total of 201 specimens of liquid-based thin-layer cytological examination
      findings were collected and detected by HPV DNA test and hTERC detected by FISH.
      All women underwent colposcopy and histological examination of biopsy specimen if
      needed. The 3 screening methods were compared based on histological examination
      of colposcopic biopsies. RESULTS: The amplification of hTERC showed 6.06% in
      normal or inflammation cases, 10.00% in CIN 1, 66.67% in CIN 2, 72.50% in CIN 3,
      and 100.00% in carcinoma, with significant difference between the low- (<or=CIN 1
      or <or=low-grade squamous intraepithelial lesion) and high-grade (>or=CIN 2 or
      >or=atypical squamous cells in which high-grade squamous intraepithelial lesion
      cannot be excluded) cervical lesions (P < 0.001). The hTERC amplification rate
      was consistent with abnormal rates of cytological and histological diagnoses. The
      detection of hTERC amplification had a much higher accuracy (87.56%) than the
      cytological (80.10%) and HPV DNA test (77.61%) findings. CONCLUSIONS: Using FISH
      to detect the amplification of hTERC had a much higher specificity and accuracy
      for the diagnoses of high-grade CIN and cervical cancer than cytological and HPV
      DNA test findings, suggesting that this detection might be a useful and specific
      screening method in cervical cancer and precancerous lesions.

PMID- 20686385
TI  - Vaginal and (uncommon) cervical cancers in the Netherlands, 1989-2003.
AB  - BACKGROUND: The clinical and prognostic evaluation of cervical and vaginal tumors
      other than squamous cell and adenocarcinomas is hampered by the low incidence,
      and clinical and epidemiological studies on these uncommon tumors are scarce.
      Having close affinity with the pathology laboratories, the Netherlands Cancer
      Registry offers a great opportunity to study frequency, stage, treatment, and
      survival of uncommon tumors in the cervix and vagina and separately, the clear
      cell adenocarcinoma of the vagina and cervix. METHODS: All invasive cervical
      tumors (n = 10,570) and all in situ and invasive vaginal tumors (n = 778)
      diagnosed in the Netherlands during 1989-2003 were selected from the Netherlands
      Cancer Registry. Age, stage at diagnosis, and treatment were described for each
      histological subgroup to find differences between common and uncommon tumors,
      including 5-year relative survival rates. RESULTS: Twenty-five patients (3%) with
      cervical cancer subsequently developed a vaginal tumor (during 1989-2003), and 19
      of these patients underwent hysterectomy for their cervical cancer. A
      significantly worse prognosis was found for patients with small cell
      neuroendocrine cervical tumors and for patients with vaginal melanomas. Patients
      with clear cell adenocarcinoma of the vagina and cervix were found across all age
      categories. CONCLUSIONS: The less common histological types of cervical and
      vaginal cancers were clearly different from squamous cell carcinomas, especially
      with respect to age at diagnosis and survival rates. Spreading population-based
      knowledge of effects of treatment of these uncommon tumors should help clinical
      decision making and therefore improve prognosis.

PMID- 20686386
TI  - Period prevalence and risk factors for postoperative short-term wound
      complications in vulvar cancer: a cross-sectional study.
AB  - INTRODUCTION: Although clinicians recognize that postoperative wound management
      in patients with vulvar cancer (VC) is challenging, the prevalence and risk
      factors for different types of short-term wound complications (WCs) remain
      unclear. The aims of this study were: (1) to determine the period prevalence of
      postoperative short-term WCs and (2) to identify risk factors associated with
      short-term WCs in patients with VC. METHOD: In a cross-sectional study in a Swiss
      University Hospital, a sample of 108 patients with VC treated surgically (and
      free of WCs at the time of admission) was included. Data were collected
      retrospectively from 2007 to 1997 from medical records using an investigator
      developed data collection instrument to assess risk factors preoperatively and
      perioperatively and WCs that occurred within the first 30 postoperative hospital
      days. The period prevalence of WCs was calculated, and logistic regression was
      used to identify risk factors for WCs. RESULTS: The median age was 69 years
      (interquartile range [IQR], 21 years). The period prevalence of WCs was 45.4%
      (49/108), showing at least 1 of 8 assessed WCs per patient within the median
      hospital duration of 11 days (IQR, 12 days). The period prevalence for each type
      of WC was 31.5% for dehiscence, 12% for hematoma, 6.5% for necrosis, 5.6% for
      infections, 4.6% for seroma, 1.9% for lymph cysts, 1.9% for malignant wounds, and
      0% for disturbed tissue formation. Two significant predictors of WCs were
      identified out of 14 risk factors examined (P < 0.05). The odds ratio (OR) for WC
      increased with the extent of surgical therapy, ie, from excision to
      hemivulvectomy and to radical vulvectomy, by a factor of 2.6 (OR, 2.6; 95%
      confidence interval [CI], 1.34-5.14), and, in the case of inguinofemoral
      lymphadenectomy, by a factor of 3 (OR, 3.0; 95% CI, 1.03-8.76). CONCLUSION: The
      high prevalence of short-term WCs (45.4%) indicates a need for systematic wound
      assessment and early risk management--especially after hemivulvectomy, radical
      vulvectomy, and inguinal lymphadenectomy.

PMID- 20686387
TI  - Bibliography current world literature.

PMID- 20686388
TI  - The effects of disease stage and acute-on-chronic liver failure on the profile of
      plasma dimethylarginines in cirrhosis.

PMID- 20686390
TI  - Another manager's problem?

PMID- 20686391
TI  - Emergency department utilization by insured users: a study of motivating factors.
AB  - Emergency departments (EDs) represent a critical entryway into America's health
      care delivery system and are under significant pressure. This study seeks to
      understand why insured patients use EDs rather than more appropriate medical
      alternatives available to reduce the strain they are placing on this critical
      portal of entry. This exploratory research study surveyed insured patients
      presenting to 1 of 4 Central Florida EDs. Factor analysis and cluster analysis
      were used to identify groups of insured ED users defined by motivating factors.
      This study found that there exists a disconnect between insured individuals and
      the primary care system.

PMID- 20686392
TI  - Your workers may be contingent but your liability for them is certain: Part III:
      other employment issues.
AB  - Hiring contingent workers can significantly help health care employers reduce
      labor costs while maintaining the staff required for quality patient care.
      However, a number of federal laws create legal land mines that await the
      unsuspecting employer. This article, the concluding part of a 3-part examination
      of contingent employment, addresses additional issues including benefits, tax
      implications, workers' compensation, contract considerations, and the screening
      of potential staffing partners.

PMID- 20686393
TI  - The future of retail clinics: in a volatile health care environment.
AB  - Recent estimates put the total number of retail clinics at more than 1000
      nationwide. Some forecasts estimate that explosive growth will continue in the
      future, whereas others suggest that the retail clinic boom might be ending. This
      article assesses the retail clinic trend and explores its future viability in the
      volatile health care environment. Eight administrative and clinical leaders in 7
      health systems that are affiliated with or own retail clinics were asked specific
      questions about the future evolution of retail clinics. Respondents offered mixed
      opinions about the future of retail clinics, and most were skeptical about their
      growth potential. Some of the respondents believed that health care reform will
      be supportive of retail clinics, but there was uncertainty about the specific
      effects of expansion in insurance coverage. Respondents reacted differently to
      the prospect of retail clinics expanding their scope of practice to include
      chronic conditions. Some of them welcomed the trend, but the majority was
      critical of it for various reasons. At this turning point for the health care
      system, it is not clear whether retail clinics will represent a significant value
      proposition for the system or whether they are a fad that will soon pass and
      disappear.

PMID- 20686395
TI  - Patients are not always rational: the leadership challenge to improve patient
      satisfaction scores.
AB  - Health care managers today are faced with the awesome challenge not only of
      meeting patient and guest expectations in health care but also in achieving
      competitive patient satisfaction scores. With the move toward increased
      transparency in health care quality along with regular reporting patient
      satisfaction scores, health care managers must confront the many challenges and
      expectations of patients and guests. Health care managers also need to know that
      patients and guests are not always rational in their expectations and perceptions
      of health care services and therefore may report invalid and unreliable
      experiences in a patient satisfaction survey. This article addresses these
      challenges and provides recommendations for improving patient satisfaction.

PMID- 20686396
TI  - Consumer-directed health plans: are medical and health savings accounts viable
      options for financing American health care?
AB  - When Americans voted in November 2008, many had the presidential candidates'
      positions on health care reform in mind. Health savings accounts, which are high
      deductible health plans coupled with a tax-protected savings account, are 1 type
      of consumer-directed health plan (CDHP) that gained strong support from the Bush
      administration. Despite evidence of the effectiveness of CDHPs in constraining
      costs in other countries, the Obama health plan contains no mention of their role
      in future US health reform. This article seeks to provide the reader with a
      better understanding of how CDHPs can help to improve the use of health resources
      and reduce national health care expenditures by exploring the history and
      previous research on several types of consumer-directed plans and by providing a
      comparative analysis of the use of CDHPs in other countries.

PMID- 20686397
TI  - Hospital chief executive officer perspective on professional development
      activities.
AB  - A study was undertaken to develop understanding of hospital chief executive
      officers' (CEOs') perspectives concerning importance and impact of professional
      development activities in US hospitals. It was also intended to reveal CEO
      preferences for various modalities of professional development including
      membership in professional societies, attainment of credentials, and coaching by
      mentors. A mail survey of 582 hospital CEOs made use of a pilot-tested
      questionnaire with 30 close ended multipart questions. Results showed that most
      CEOs assigned a high level of importance to professional development and favored
      conferences, seminars, and networking opportunities, but low priority assigned to
      online activities such as webinars. They reported lending support to senior
      managers for participation in these activities by providing financial resources
      and by allowing time off to engage in these activities. The respondents indicated
      that the importance of various modalities of professional development has either
      increased or remained high over the recent 5 years. Conclusions suggest that
      verifiable quantitative data are needed for understanding of the frequency of
      participation and resource commitment of health care organizations toward the
      professional development of CEOs and senior managers. The results of this
      perceptual study reveal a high level of importance accorded to various forms of
      professional development activities by the participating CEOs.

PMID- 20686398
TI  - Health care managers as educational evaluators and accreditation support
      personnel.
AB  - Although health care managers and administrators are often heralded as the
      foundational support for multifaceted health care institutions, few have been
      duly credited for their role in evaluating students that they train and precept
      in the clinical arena. Likewise, the uses and magnitude of the evaluations are
      often underestimated. This article presents an overview of the traditional role
      of health care managers, along with their expanded role as evaluators of students
      in clinical settings. This article also highlights the use of the evaluations
      from 35 health care managers in the professional development of students and as
      accreditation support for a university's business college.

PMID- 20686399
TI  - Exploring nurses' perceptions of organizational factors of collaborative
      relationships.
AB  - Collaborative relationships are influenced by the context of the organization in
      which health professionals work. There is limited knowledge concerning the
      influence that organizational factors have on this process. A descriptive study
      design using semistructured interviews was used to explore nurses' perceptions of
      the organizational factors that influence the development of collaborative
      relationships in health care teams. Eight nurses from a university-affiliated
      teaching hospital in Montreal participated in this study. Nurses described a
      variety of experiences where effective collaboration took place. One common theme
      emerged from the participants: Being Available for Collaboration. Nurses
      perceived that 2 particular organizational factors-time and workday scheduling
      influenced the development of collaborative relationships. This study supports
      the need for health care managers to promote and invest in alternative means of
      communication technology and to structure clinical care environments to help
      promote the development of collaborative relationships within health care teams.

PMID- 20686400
TI  - See your ideas in print: write for a professional journal.
AB  - Those who have sometimes thought about writing for a professional journal should
      be encouraged by the fact that most journal writers are the same as journal
      readers-practitioners and educators who have something of potential value to
      share with others. There are career-enhancing advantages in journal writing, and
      there can be a significant amount of personal satisfaction as well. Succeeding at
      writing and placing a journal article requires the following: selecting an
      appropriate topic; knowing the publication and its audience and framing the
      article in the appropriate style; working with the journal editor to create an
      acceptable manuscript, which includes responding positively to the editor's
      criticisms and suggestions; and observing all submission requirements and
      deadlines. One who follows this entire process to its positive conclusion will
      find that journal writing can be an exacting, demanding, frustrating, and
      immensely satisfying professional activity.

PMID- 20686401
TI  - Multidetector computed tomography follow-up of hypoattenuating small liver
      lesions in patients with rectal cancer.
AB  - OBJECTIVE: To study the behavior of hypoattenuating liver lesions, deemed too
      small to characterize at baseline scanning with multidetector computed tomography
      (CT), in patients with rectal cancer. METHODS: Retrospective review of locally
      advanced rectal cancer patients from a radiation oncology therapy database was
      conducted. Patients who presented before neoadjuvant chemoradiation without
      metastases at baseline CT and with follow-up scans for at least 1 year after
      therapy were evaluated. CT studies were reviewed for the presence and change in
      size of hypoattenuating liver lesions (<15 mm) at baseline and follow-up.
      RESULTS: A total of 616 consecutive patients from the radiotherapy database were
      reviewed. Of these, 70 patients with a total of 163 hepatic lesions met the
      selection criteria. The mean patient age was 62.4 years (range, 26-85 years). All
      patients subsequently underwent surgery and adjuvant chemotherapy. The mean time
      of radiographic imaging from baseline CT to most recent surveillance CT was 3.3
      years (range, 1.1-7.4 years). Two radiologists independently reviewed the CTs.
      The lesions were stable in 56 of 70 (80.0%, 95% confidence interval: 69%, 89%)
      patients. Of 163 lesions, 148 (90.8%) were stable, 8 (4.9%) regressed, and 7
      (4.3%) progressed in size. No significant difference in results was found for
      patients stratified according to T-stage (P = 0.41) and N-stage (P > 0.99).
      CONCLUSION: In patients with rectal cancer, majority of small hypoattenuating
      liver lesions remain stable and are treated as benign lesions, at multidetector
      CT follow-up of more than a year. Nevertheless, hepatic lesion stability during
      systemic therapy should still be interpreted with caution and closely followed
      for at least 1 year after completion of therapy.

PMID- 20686402
TI  - Clinical results of definitive chemoradiotherapy for patients with synchronous
      head and neck squamous cell carcinoma and esophageal cancer.
AB  - OBJECTIVES: To assess the efficacy and toxicity of radical chemoradiotherapy for
      patients with synchronous head and neck squamous cell carcinoma (HNSCC) and
      esophageal cancer (EC). METHODS: Thirty-four patients with synchronous HNSCC and
      EC were treated mainly with radical chemoradiotherapy at the same time. Median
      external radiation dose for HNSCC and EC was 70 Gy (range, 60-70.5 Gy), except
      for 2 patients with tongue cancer, who underwent brachytherapy and 60 Gy (range,
      45-70 Gy), respectively. Thirty-one patients were treated with concurrent
      chemoradiotherapy with cisplatin and/or 5-fluorouracil or TS-1 (oral anticancer
      agent that combines tegafur, a metabolically activated prodrug of 5-fluorouracil,
      with 5-chloro-2, 4-dihydoroxypyridine, and potassium oxonate). RESULTS: Thirty
      three patients completed the intended treatment. The response rate was 94%, with
      26 complete responses (76%) and 6 partial responses (18%). At a median follow-up
      of 17.3 months, 2-year rates of overall survival, cause-specific survival, and
      disease-free survival were 44%, 52%, and 33%, respectively. Initial failure
      patterns were local failure in 14 patients (63%), regional progression in 3
      patients (13%), and distant metastasis in 6 patients (27%). The most common acute
      toxicity was myelosuppression, with 8 patients experiencing grade 3-4 toxicity.
      Three patients experienced grade 3 mucositis and pharyngitis. No patients
      experienced late morbidity of grade 3 or higher. CONCLUSIONS: Definitive
      chemoradiotherapy for patients with synchronous HNSCC and EC is feasible with a
      low mortality rate and acceptable morbidity.

PMID- 20686403
TI  - Targeting mutated K-ras in pancreatic adenocarcinoma using an adjuvant vaccine.
AB  - PURPOSE: Codon 12 mutations of K-ras are frequent in pancreatic adenocarcinoma,
      and represent potential tumor-specific neoantigens. The objective of this study
      was to assess the safety and efficacy of immunizing patients with resected
      pancreatic cancer with a vaccine targeted against their tumor-specific K-ras
      mutation. METHODS: Patients with resected pancreatic cancer, with K-ras mutations
      at codon 12, were vaccinated once monthly for 3 months with a 21-mer peptide
      vaccine containing the corresponding K-ras mutation of the patient's tumor. About
      200 MUg of peptide vaccine was injected intradermally on day 7 of a 10-day course
      of intradermal granulocyte macrophage colony-stimulating factor. Toxicity was
      assessed by National Cancer Institute Common Toxicity Criteria v2.0. Immune
      responses were evaluated by delayed-type hypersensitivity (DTH) tests and the
      enzyme-linked immunosorbent spot assays. RESULTS: Of 62 screened patients, 24
      were vaccinated. There were no grade 3-5 vaccine-specific toxicities. The only
      National Cancer Institute grade 1 and 2 toxicity was erythema at the injection
      site (94%). Nine patients (25%) were evaluable for immunologic responses. One
      patient (11%) had a detectable immune response specific to the patient's K-ras
      mutation, as assessed by DTH. Three patients (13%) displayed a DTH response that
      was not specific. Median recurrence free survival time was 8.6 months (95%
      confidence interval, 2.96-19.2) and median overall survival time was 20.3 months
      (95% confidence interval, 11.6-45.3). CONCLUSIONS: K-ras vaccination for patients
      with resectable pancreatic adenocarcinoma proved to be safe and tolerable with
      however no elicitable immunogenicity and unproven efficacy. Future development of
      adjuvant vaccine therapies should use more immunogenic vaccines.

PMID- 20686404
TI  - Prospective evaluation of a 12-week walking exercise program and its effect on
      fatigue in prostate cancer patients undergoing radical external beam
      radiotherapy.
AB  - OBJECTIVE: To evaluate tolerability and compliance to a walking exercise program
      and its effect on fatigue during and after radical external beam radiation
      therapy (EBRT) for prostate cancer. METHODS: A total of 50 subjects with prostate
      cancer undergoing EBRT over 6 to 8 weeks were prospectively accrued to an
      exercise intervention group, matched for age and clinical characteristics to 30
      subjects in a historical control group who underwent EBRT with no specific
      exercise intervention. Starting 1 week before EBRT, exercise participants
      performed moderate-intensity walking targeting 60% to 70% age-predicted maximum
      heart rate, at least 20 min/d, 3 d/wk over 12 weeks. The Brief Fatigue Inventory
      was administered at baseline, mid-EBRT (week 3-4), end-EBRT (week 6-8), and 6
      months post-EBRT. RESULTS: Of 50, 42 (84%) of exercise participants completed the
      walking program. There were no cardiovascular complications, musculoskeletal
      injuries, or other adverse events. A total of 89% subjects reported "Good
      Excellent" satisfaction during and up to 6 months post-EBRT. Fatigue in control
      subjects escalated from baseline to end-EBRT, remaining high at 6 months post
      EBRT (P[r] = 0.03). In contrast, mean total fatigue scores in exercise subjects
      were stable from baseline up to 6 months post-EBRT (P = 0.52). Trends for higher
      fatigue interference with quality of life were observed in the control group as
      compared with the exercise group. CONCLUSIONS: Moderate-intensity walking
      exercise during radical EBRT is safe and feasible. The high convenience and
      satisfaction ratings, in conjunction with the observed fatigue trends, indicate
      that this activity has the potential to attenuate fatigue and improve quality of
      life for patients with localized prostate cancer undergoing curative therapy.

PMID- 20686405
TI  - Outcomes after trimodality therapy for esophageal cancer: the impact of histology
      on failure patterns.
AB  - OBJECTIVES: This retrospective analysis of patients undergoing neoadjuvant
      chemoradiation followed by surgical resection was performed to determine if
      histology or pathologic response affected local-regional control (LRC), survival
      outcomes or patterns of failure. METHODS: We performed a review of 164 patients
      who underwent neoadjuvant chemoradiation followed by surgical resection from 1992
      to 2006 for esophageal cancer. Information on patient characteristics, pathologic
      response, failure patterns, and survival was collected. Survival was estimated by
      the Kaplan-Meier method, and Cox multivariable Regression model was used to
      analyze trends. RESULTS: The median follow-up was 18 months and 27 months in
      surviving patients. The 3-year overall survival (OS) and LRC was 46% and 79%. The
      overall response for the entire cohort included a pathologic complete response
      (pCR) rate of 41.4%, 21.3% with microscopic residual disease (mRD) and 36.3% with
      gross residual disease (gRD). The 3-year OS of patients who achieved a pCR versus
      mRD versus gRD was 58%, 53%, and 29%. OS was significantly improved in patients
      with a pCR and mRD compared with gRD (P = 0.001). On multivariate analysis both
      pCR and mRD correlated with an improved OS. Squamous cell cancers (SCC) had a
      higher rate of pCR than adenocarcinomas (AC), 54% versus 34.8% (P = 0.01). The 3
      year LRC for patients with SCC and AC was 100% and 71% (P = 0.03). Among SCC with
      recurrence, there were no local failures and all failed distantly (P = 0.001).
      CONCLUSIONS: Patients with microscopic residual disease following trimodality
      therapy had similar outcomes to patients achieving a pCR. Patients with SCC were
      more likely to achieve a pCR, and had a higher propensity to fail distantly when
      compared with patients with AC. This data should be considered in the design of
      future clinical trials.

PMID- 20686406
TI  - Concurrent cetuximab with stereotactic body radiotherapy for recurrent squamous
      cell carcinoma of the head and neck: a single institution matched case-control
      study.
AB  - PURPOSE: Locally recurrent head and neck squamous cell carcinoma can be treated
      with curative intent by surgical salvage or reirradiation with or without
      chemotherapy. We have previously demonstrated the feasibility and safety of
      stereotactic body reirradiation at our institution; however, efficacy has been
      unsatisfactory. Based on the successful combination of cetuximab with
      radiotherapy in locally-advanced squamous cell carcinoma of the head and neck, we
      compared stereotactic body radiotherapy alone with combination therapy, using
      concomitant cetuximab with stereotactic body radiotherapy, to enhance clinical
      efficacy while minimizing toxicity. METHODS: In a retrospective-matched cohort
      study, we compared 2 groups of patients treated over a 6-year period with
      stereotactic body radiation therapy alone (n=35) or with weekly cetuximab
      infusion during stereotactic body radiotherapy (n=35), and evaluated clinical
      response, local control, overall survival, and toxicity. Cox proportional hazard
      models were used to assess independent prognostic factors. RESULTS: The median
      follow-ups for patients alive at last contact were 21.3 months and 24.8 months
      for stereotactic body radiotherapy only (n=13) and stereotactic body radiotherapy
      plus cetuximab (n=22), respectively. Our results indicate that cetuximab
      conferred an overall survival advantage (24.5 vs. 14.8 months) when compared with
      the stereotactic body radiotherapy alone arm, without a significant increase in
      grade 3/4 toxicities. This survival advantage was also observed in the subgroup
      that had received cetuximab therapy during their prior therapeutic regimen.
      CONCLUSIONS: Our results suggest an overall survival benefit of concomitant
      cetuximab with stereotactic body radiotherapy in locally recurrent head and neck
      squamous cell carcinoma, and suggest a role in this setting. Concomitant
      cetuximab with stereotactic body radiotherapy is a reasonable approach for
      unresectable recurrent squamous cell carcinoma of the head and neck, and should
      be tested in prospective randomized trials to validate its clinical efficacy.

PMID- 20686407
TI  - Role of androgen deprivation treatment in patients with castration-resistant
      prostate cancer, receiving docetaxel-based chemotherapy.
AB  - OBJECTIVES: To assess the impact of continued androgen deprivation therapy (ADT)
      in patients with castration-resistant prostate cancer (CRPC) receiving first-line
      docetaxel-based chemotherapy. METHODS: A retrospective review was performed on 78
      patients fulfilling the criteria for CRPC who were treated with docetaxel-based
      chemotherapy over 5 years. RESULTS: Thirty-nine patients received concurrent ADT
      (ADT group), whereas 39 patients discontinued ADT (No-ADT group). PSA response
      rates were 66.7% for ADT patients and 48.7% for No-ADT patients (P = 0.27). The
      median progression-free survival and overall survival were 5.0 months and 24.8
      months for ADT patients and 4.9 months and 22.1 months for No-ADT patients,
      respectively (P = 0.57, P = 0.94). Follow-up testosterone levels were available
      in 13 patients of the No-ADT group and none of them recovered a normal serum
      testosterone level over a median follow-up duration of 8.3 months from ADT
      discontinuation. ADT was recommenced in 21 of 39 patients in the No-ADT group
      and, of these, 6 (29%) achieved a PSA response. CONCLUSION: Clinical outcomes
      were not significantly different when patients with CRPC received concurrent ADT,
      or were not so treated, when receiving first-line docetaxel-based chemotherapy.
      Despite ADT withdrawal, serum testosterone level did not recover to the
      noncastrated level during the period of chemotherapy, and reinduction of hormone
      sensitivity occurred in about one-quarter of patients.

PMID- 20686408
TI  - An unusual cause of death in poisoning: a case report.
AB  - Arterioesophageal fistula is a rare cause of upper gastrointestinal tract
      bleeding. Arterioesophageal fistula and haematemesis are rare in poisoning,
      especially in noncorrosive poisoning. An arterioesophageal fistula can occur in
      patients with retroesophageal subclavian artery. This is usually associated with
      prolonged presence of nasogastric tube.

PMID- 20686409
TI  - Electrical compound action potentials recorded with automated neural response
      telemetry: threshold changes as a function of time and electrode position.
AB  - OBJECTIVE: Since the introduction of neural response telemetry (NRT) for the
      Nucleus 24 cochlear implant (CI24), researchers and clinicians have investigated
      the feasibility of using the electrically evoked compound action potential (ECAP)
      threshold to objectively predict psychophysical measurements that are used in the
      programming of the speech processor. The ability to substitute objective for
      behavioral measurements, particularly measurements made at the time of surgery,
      would greatly facilitate programming the MAP for young children and other
      individuals who are not able to provide reliable behavioral data required for MAP
      programming. There have been a number of studies that have examined
      characteristics of the ECAP measured at the time of surgery and postoperatively;
      however, all the available published data are based on the CI24. With the
      introduction of the Nucleus Freedom device, an automated NRT (AutoNRT) program
      became available, which was capable of measuring ECAP thresholds at lower levels
      than was previously possible with NRT software associated with the CI24 device.
      It was hypothesized that the enhancements to the NRT program may improve the
      predictability of postoperative measurements from intraoperatively recorded ECAP
      thresholds. The purpose of this study was to track ECAP thresholds obtained using
      AutoNRT as a function of time and electrode position. DESIGN: ECAP thresholds
      were recorded from 71 children and adults implanted with the Nucleus Freedom
      device using the AutoNRT test protocol. ECAP thresholds were obtained at the time
      of surgery, at initial stimulation, and 3 mos poststimulation. Five electrodes
      located at basal, middle, and apical positions in the cochlea were tested at each
      time interval and thresholds were compared. RESULTS: Significant differences were
      found in ECAP thresholds measured with AutoNRT as a function of both time and
      electrode position. Basal electrodes had higher ECAP thresholds than apical
      electrodes and that relationship was consistent for each time period. Thresholds
      for all electrodes decreased between surgery and initial stimulation and remained
      relatively stable at 3 mos poststimulation. ECAP thresholds were consistently
      lower for children compared with adults at each time point. Mid-array electrodes
      (11 and 16) showed the least amount of change over time. CONCLUSIONS: AutoNRT
      thresholds demonstrated significant change over time, limiting the ability to use
      intraoperatively recorded ECAP thresholds to predict postoperative measurements.
      In this study, electrodes 11 and 16 showed the least amount of change in ECAP
      threshold over time and therefore would be the best choices for estimating
      postoperative ECAP thresholds. Although not an ideal solution, mid-array ECAP
      thresholds obtained intraoperatively may prove to be helpful in creating a first
      MAP when no other behavioral or electrophysiological data are available.

PMID- 20686410
TI  - The NOSE study (nasal ointment for Staphylococcus aureus eradication): a
      randomized controlled trial of monthly mupirocin in HIV-infected individuals.
AB  - BACKGROUND: HIV-positive patients at HELP/PSI, Inc, an in-patient drug
      rehabilitation center, had a high baseline prevalence of Staphylococcus aureus
      colonization (49%) and incidence of infection (17%) in a previous year-long
      study. METHODS: A randomized, double-blinded, placebo-controlled study was
      conducted to determine whether repeated nasal application of mupirocin ointment
      would decrease the odds of S. aureus nasal colonization in 100 HELP/PSI patients
      over an 8-month period. A 5-day course of study drug was given monthly, and
      colonization was assessed at baseline and 1 month after each treatment. S. aureus
      infection was a secondary outcome. RESULTS: In repeated-measures analysis,
      mupirocin reduced the odds of monthly S. aureus nasal colonization by 83%
      compared with placebo [adjusted odds ratio (ORadj) = 0.17; P < 0.0001]. Subjects
      colonized at study entry had a 91% reduction in subsequent colonization (ORadj =
      0.09; P < 0.0001). Mupirocin also suppressed S. aureus colonization in subjects
      not colonized at baseline (ORadj = 0.23; P = 0.006). There was no difference in
      infection rates between the mupirocin and placebo groups (hazard ratio = 0.49, P
      = 0.29). CONCLUSIONS: Monthly application of nasal mupirocin significantly
      decreased S. aureus colonization in HIV patients in residential drug
      rehabilitation. Monthly mupirocin application has a potential role in long-term
      care settings or in HIV-positive patients with high rates of S. aureus
      colonization and infection.

PMID- 20686412
TI  - Ascaris-induced eosinophilic myocarditis presenting as acute ST elevation
      myocardial infarction and cardiogenic shock in a young woman.

PMID- 20686413
TI  - Hybrid repair of aortic arch aneurysm in high-risk patients.
AB  - OBJECTIVES: Morbidity and mortality after conventional surgery of aortic arch
      aneurysms remain high. Alternative techniques are the subject of this report.
      METHODS AND RESULTS: Open surgery requires cardiopulmonary bypass and hypothermic
      circulatory arrest. Thoracic endovascular aneurysm repair has a less invasive
      therapeutic alternative. The number of high-risk patients has considerably
      increased over the past decade. The proximity of the aneurysm to the supraaortic
      vessels makes it difficult to achieve a satisfactory proximal landing zone for
      endovascular stenting. Two methods have been proposed to address this issue:
      branched stent grafts and extraanatomic bypass, defined as a hybrid approach,
      which combines aortic debranching and endovascular procedures. Experience with
      hybrid repair is limited. Today there are no formal guidelines for the management
      of aortic arch aneurysm in high-risk patients. CONCLUSION: Hybrid repair of
      aortic arch aneurysm in high-risk patients is a feasible and safer option.

PMID- 20686414
TI  - Cardiovascular magnetic resonance of acute myocardial infarction following
      traumatic coronary artery dissection.
AB  - Traumatic coronary artery dissection is a very rare cause of myocardial
      infarction. Occurrence of this condition late in the posttraumatic period is
      extremely uncommon. We present a case of a young patient with acute myocardial
      infarction 4 weeks after blunt chest trauma. Coronary angiography showed left
      anterior descending artery dissection as well as thrombus formation, and multiple
      small infarctions were shown by cardiovascular magnetic resonance. 

PMID- 20686415
TI  - Inadvertent placement of left ventricular endocardial pacing lead.

PMID- 20686411
TI  - Evolution of drug resistance during 48 weeks of zidovudine/lamivudine/tenofovir
      in the absence of real-time viral load monitoring.
AB  - OBJECTIVES: To describe the resistance mutations selected by a first-line regimen
      of zidovudine/lamivudine/tenofovir in the absence of real-time viral load
      monitoring. DESIGN: A substudy of 300 participants from the Development of
      Antiretroviral Therapy in Africa trial in Uganda and Zimbabwe, which compared
      managing antiretroviral therapy with and without laboratory monitoring. METHODS:
      Stored plasma samples from selected time points were assayed retrospectively for
      HIV-1 RNA. The pol gene in all baseline samples and those with HIV RNA >1000
      copies per milliliter at weeks 24 and 48 were sequenced. RESULTS: The proportion
      with HIV RNA >1000 copies per milliliter increased from 15% at 24 weeks to 24% at
      48 weeks. Eighteen of 31 (58%) genotyped samples at 24 weeks had >= 1 major
      nucleoside reverse transcriptase inhibitor-associated mutations compared with 41
      of 47 (87%) at 48 weeks. Excluding 1 nonadherent patient, a mean of 2.0 (95%
      confidence interval: 1.3 to 2.8) thymidine analogue mutations (TAMs) developed
      between weeks 24 and 48 among 14 patients with HIV RNA >1000 copies per
      milliliter at both time points. K65R was detected in 8 of 63 (13%) patients and
      was negatively associated with number of TAMs (P = 0.01) but not viral subtype (P
      = 0.30). CONCLUSIONS: A high rate of acquisition of TAMs, but not of K65R, among
      patients with prolonged viraemia was observed. However, most patients were
      virologically suppressed at 48 weeks, and long-term clinical and immunological
      outcomes in the Development of Antiretroviral Therapy in Africa trial were
      favorable.

PMID- 20686416
TI  - Fracture of coronary artery sirolimus eluting stent with formation of four
      aneurysms.
AB  - Coronary stent fracture is a relatively rare but potentially serious complication
      of coronary artery stenting, in particular with sirolimus-eluting stents. It has
      been recognized as one possible cause of in-stent restenosis as well as acute
      stent thrombosis. The formation of coronary artery aneurysm is one of the
      critical complications after percutaneous coronary intervention and it has been
      described after a stent fracture too. We report here a case of formation of four
      coronary artery aneurysms associated with the fracture of a sirolimus-eluting
      stent. 

PMID- 20686417
TI  - What does the future hold for niacin as a treatment for hyperlipidaemia and
      cardiovascular disease?
AB  - Statin therapy is widely used in treatment and prevention of cardiovascular
      disease (CVD). It is well established that statin therapy is not associated with
      significant increase in high-density lipoprotein cholesterol (HDL-c) or
      significant decrease in triglyceride level. Importantly, emerging evidence has
      suggested that low HDL-c and high triglyceride are strong risk factors associated
      with CVD. Niacin is a unique lipid-lowering medication with a capacity to lower
      low-density lipoprotein cholesterol (LDL-c), triglyceride and increase HDL-c. In
      this context, there is considerable interest in trials involving niacin as
      monotherapy and in association with statins. Recent trials showed that the
      combination of statin and niacin is an effective treatment not only for
      dyslipidaemia (high LDL-c, high triglyceride and low HDL-c) but also for carotid
      intima-media thickness, one of the important features of atherosclerosis.
      Furthermore, niacin is distinguished by its unique capacity to effectively lower
      lipoprotein (a) [Lp(a)] levels. Flushing is the only factor that limits the wide
      use of niacin. The combination of statin and niacin has potential as a future
      treatment of atherogenic dyslipidemias; however, further evidence is needed.
      Importantly, the impact of niacin and statin on insulin sensitivity is not yet
      known. This article projects the potential benefits of current and possible
      future niacin clinical trials.

PMID- 20686418
TI  - Trileaflet pulmonary valve atresia.

PMID- 20686419
TI  - Successful use of therapeutic mild hypothermia after cardiac arrest.

PMID- 20686420
TI  - Atrioventricular 2:1 block as clinical presentation of a septal mass causing left
      ventricular outflow tract obstruction.
AB  - We report the case of a 56-year-old woman with effort angina, dyspnea and a
      septal mass causing atrioventricular block, treated with pacemaker implantation,
      and left ventricular outflow tract obstruction (induced by septal mass protrusion
      into left ventricular cavity). 

PMID- 20686421
TI  - Plasma glucose and not hemoglobin or renal function predicts mortality in
      patients with STEMI complicated with cardiogenic shock.
AB  - OBJECTIVE: To assess the predictive value of three biomarkers for mortality in ST
      segment elevation myocardial infarction (STEMI) with cardiogenic shock.
      BACKGROUND: STEMI complicated by cardiogenic shock accounts for the majority of
      STEMI related deaths. Patients with STEMI and hyperglycemia, anemia or kidney
      dysfunction on admission have a poor prognosis. As data on the combination of
      those three established predictors of mortality are sparse in STEMI with
      cardiogenic shock, the objective of the current study was to investigate their
      predictive value in STEMI patients with cardiogenic shock. METHODS AND RESULTS:
      Between 1997 and 2005, a total of 3038 patients presented with STEMI and were
      treated with percutaneous coronary intervention (PCI). On admission 292 patients
      presented with cardiogenic shock. Glucose, hemoglobin and creatinine clearance
      were available in 183 out of 292 patients. Overall 1-year mortality was 34%. In
      multivariate logistic regression analysis, only glucose remained a strong
      independent predictor for mortality. The odds for mortality increased by 11% for
      each 1 mmol/l increase in glucose (OR 1.11, 95% CI 1.02-1.21, P = 0.013).
      CONCLUSION: Hemoglobin and creatinine clearance bear no prognostic value. Only
      admission glucose levels strongly and independently predict 1-year mortality in
      STEMI patients with cardiogenic shock and treated with PCI.

PMID- 20686422
TI  - Pilot testing of function-focused care for acute care intervention.
AB  - The purpose of this study was to test the feasibility of a function-focused care
      for acute care intervention and explore the impact of this intervention on
      nurses' knowledge, beliefs, and behavior associated with engaging patients in
      functional and physical activities. Pre- and posttesting was performed with 23
      nurses, with posttesting at the end of the 6-month intervention period. Pilot
      testing provided some support for the feasibility of the study and showed a
      significant improvement in self-efficacy expectations but no change in the other
      study outcomes.

PMID- 20686423
TI  - Renal Fanconi syndrome secondary to deferasirox: where there is smoke there is
      fire.

PMID- 20686424
TI  - The role of angiogenesis in the transformation of plexiform neurofibroma into
      malignant peripheral nerve sheath tumors in children with neurofibromatosis type
      1.
AB  - PURPOSE: The role of angiogenesis in the transformation of peripheral
      neurofibroma (PNF) to malignant peripheral nerve sheath tumor (MPNST) in
      neurofibromatosis type 1 (NF1) remains elusive and forms the objective of this
      study. EXPERIMENTAL DESIGN: Archival tissue from 5 children with NF1 and PNF, who
      developed MPNST between the ages of 8 and 15 years were analyzed for differences
      in microvasculature. The role of proangiogenic growth factors such as Vascular
      Endothelial Growth Factor (VEGF), and its receptors Flk-1 and Flt-1, and vessel
      maturity, defined as von Willebrand factor (vWf), alpha-smooth muscle actin+
      (SMA+), were evaluated by immuno-histochemistry. RESULTS: A qualitative
      evaluation of the vasculature showed predominantly alpha-SMA+/vWf+ more stable
      vessels in PNF, and an irregular meshwork of alpha-SMA-/vWf+ endothelial cells
      structures in MPNST. In NF and PNF tumor cells were VEGF-, in contrast to VEGF+
      tumor cells in MPNST. If present, the VEGF stain was confined mainly to the
      perivascular spaces in PNF, unlike the mainly stromal VEGF stain in MPNST. VEGF
      receptors also manifested a tumor stage-specific pattern. Flk-1 and Flt-1 were
      restricted to the mature, well-formed vasculature in PNF, but exhibited a diffuse
      pattern in MPNST. CONCLUSION: Our study provides a rare opportunity to document
      consistent and histologically detectable differences in the vascular organization
      of PNF and MPNST. It permits a pair-wise evaluation of the malignant conversion
      of benign PNF into its malignant counterpart, in the same patients. The
      phenotypic variations and characteristics of the vessels in these tumors are
      consistent with the idea that a strong proangiogenic drive contributes to the
      progressive growth in MPNST.

PMID- 20686425
TI  - A family-based randomized controlled trial of pain intervention for adolescents
      with sickle cell disease.
AB  - The study had 2 aims---to determine the efficacy of a family-based cognitive
      behavioral pain management intervention for adolescents with sickle cell disease
      (SCD) in (1) reducing pain and improving health-related variables and (2)
      improving psychosocial outcomes. Each adolescent and a family support person were
      randomly assigned to receive a brief pain intervention (PAIN) (n=27) or a disease
      education attention control intervention (DISEASE ED) (n=26) delivered at home.
      Assessment of primary pain and health-related variables (health service use, pain
      coping, pain-related hindrance of goals) and secondary psychosocial outcomes
      (disease knowledge, disease self-efficacy, and family communication) occurred at
      baseline (before randomization), postintervention, and 1-year follow-up. Change
      on outcomes did not differ significantly by group at either time point. When
      groups were combined in exploratory analyses, there was evidence of small to
      medium effects of intervention on health-related and psychosocial variables.
      Efforts to address barriers to participation and improve feasibility of
      psychosocial interventions for pediatric SCD are critical to advancing
      development of effective treatments for pain. Sample size was insufficient to
      adequately test efficacy, and analyses did not support this focused cognitive
      behavioral pain management intervention in this sample of adolescents with SCD.
      Exploratory analyses suggest that comprehensive interventions, that address a
      broad range of skills related to disease management and adolescent health
      concerns, may be more effective in supporting teens during healthcare transition.

PMID- 20686426
TI  - Impact of clinical pathway on quality of care in sickle cell patients.
AB  - Clinical pathways are disease specific and are designed to standardize care. They
      are intended to serve the purpose of improving quality of care and decreasing
      healthcare and societal costs. A retrospective cross-sectional study was
      conducted comparing sickle cell patients admitted to Mercy Children's Hospital
      (MCH) from June 1999 to November 2001 before the implementation of the clinical
      care pathway (n=66), to a similar group of patients admitted from December 2001
      to July 2004 after pathway (n=121) implementation. The chi2 tests were used to
      compare categoric variables and independent t-tests for continuous variables. The
      results indicate improvement in compliance postpathway with specific care
      elements: incentive spirometry, pulse oximetry, ordering comfort measures, right
      dosage of pain medications, and achieving excellent nursing compliance in
      documenting pain scores. There was a significant decrease in the number of blood
      transfusions in postpathway patients. Though limited by sample size, the results
      suggest that clinical pathways are good tools for standardization of care in
      certain care elements and help to improve quality of care in sickle cell
      patients.

PMID- 20686427
TI  - Imbalance of plasminogen activator inhibitor type-1 (PAI-1) and tissue
      plasminogen activator (t-PA) activity in patients with Noonan syndrome.
AB  - BACKGROUND: Patients with Noonan syndrome have been reported to have an increased
      incidence of bleeding with trauma and surgery. Although various abnormalities of
      hemostasis have been described in reported series, there has been no consistent
      abnormality described and none have investigated fibrinolytic pathways. METHODS:
      Fibrinolytic parameters including tissue plasminogen activator (t-PA; activity
      and antigen), plasminogen activator inhibitor type-1 (PAI-1; activity and
      antigen), plasminogen (activity and antigen), thrombin-antithrombin complex,
      prothrombin time (PT), and activated partial thromboplastin time where studied in
      12 patients with Noonan syndrome (total of 15 data sets). PT and activated
      partial thromboplastin time were performed locally whereas the fibrinolytic
      parameters were performed in a single national reference laboratory. Individual
      results were compared with published age-appropriate norms and the mean values of
      the study patients were compared with the midpoint of normal range for each
      component measured. The ratio of PAI-1/t-PA activity was calculated for each set
      of results and compared with a "normal" value calculated from the midpoint normal
      range value for each component. RESULTS: Patients with Noonan syndrome
      consistently demonstrated an elevation of t-PA activity in relationship to PAI-1
      activity and a decreased PAI-1/t-PA ratio (P<0.01 for each comparison).
      CONCLUSIONS: Patients with Noonan syndrome seem to have an imbalance in
      fibrinolytic components favoring fibrinolysis. This may be an important
      contributor to the bleeding noted in these patients.

PMID- 20686428
TI  - Chemoradiotherapy and gefitinib in stage III non-small cell lung cancer with
      epidermal growth factor receptor and KRAS mutation analysis: cancer and leukemia
      group B (CALEB) 30106, a CALGB-stratified phase II trial.
AB  - INTRODUCTION: This study evaluated the addition of gefitinib to sequential or
      concurrent chemoradiotherapy (CRT) in unresectable stage III non-small cell lung
      cancer. METHODS: Between May 2002 and April 2005, 63 patients were entered before
      the study closing early. All received two cycles paclitaxel 200 mg/m and
      carboplatin area under the curve 6 intravenous plus gefitinib 250 mg daily. Poor
      risk stratum 1 (> or =5% weight loss and/or performance status 2) received
      radiotherapy 200 cGy for 33 fractions (6600 cGy) and gefitinib 250 mg daily. Good
      risk stratum 2 (performance status: 0-1 weight loss and <5%) received the same RT
      with gefitinib 250 mg daily and weekly paclitaxel 50 mg/m plus carboplatin AUC 2.
      Consolidation gefitinib until progression was started after all toxicities were
      grade < or =2. RESULTS: Acute high-grade infield toxicities were not clearly
      increased compared with historical CRT data. Poor-risk (N = 21) median
      progression-free survival was 13.4 months (95% confidence interval [CI]: 6.4
      25.2) and median overall survival 19.0 months (95% CI: 9.9-28.4). Good-risk (N =
      39) median progression-free survival was 9.2 months (95% CI: 6.7-12.2), and
      median overall survival was 13 months (95% CI: 8.5-17.2). Thirteen of 45 tumors
      analyzed had activating epidermal growth factor receptor (EGFR) mutations, and 2
      of 13 also had T790M mutations. Seven tumors of 45 had KRAS mutations. There was
      no apparent survival difference with EGFR-activating mutations versus wild type
      or KRAS mutation versus wild type. CONCLUSIONS: Survival of poor-risk patients
      with wild type or mutated EGFR receiving sequential CRT with gefitinib was
      promising. Survival for good-risk patients receiving concurrent CRT plus
      gefitinib was disappointing even for tumors with activating EGFR mutations.

PMID- 20686429
TI  - Treatment outcomes by tumor histology in Eastern Cooperative Group Study E4599 of
      bevacizumab with paclitaxel/carboplatin for advanced non-small cell lung cancer.
AB  - INTRODUCTION: The combination of paclitaxel/carboplatin (PC) and bevacizumab (B)
      was previously shown to extend overall survival (OS) in patients with advanced
      nonsquamous non-small cell lung cancer (NSCLC). An analysis of survival and
      safety outcomes based on histology is presented here. METHODS: Patients with
      cytologically or histologically confirmed metastatic NSCLC were treated with PC +
      B (PCB) or PC. Median OS for all patients was determined using Kaplan-Meier
      methodology. Hazard ratios (HRs) and 95% confidence intervals (CIs) were obtained
      using an unstratified Cox proportional hazards model. Histology-by-treatment
      interaction was tested with an unstratified multivariate Cox regression model.
      RESULTS: A total of 444 patients were randomized to PC, and 434 patients were
      randomized to PCB (the intent-to-treat population). Median OS times were 10.3 and
      12.3 months for PC and PCB, respectively, with an HR for PCB of 0.80 (95% CI:
      0.69-0.93). A total of 68.8% of patients had adenocarcinoma histology; 18.9% had
      "not otherwise specified"; 5.5% had large cell undifferentiated; 2.6% had
      bronchoalveolar carcinoma; and 3.9% "other." For adenocarcinoma, median OS was
      10.3 months for PC treatment (n = 302) and 14.2 months for PCB (n = 300), HR 0.69
      (95%CI: 0.58-0.83). Sample sizes for other specific histologic subtypes were too
      small for meaningful comparisons. Safety profiles among histologies were
      consistent with the overall safety profile, and there were no unexpected adverse
      event trends. CONCLUSIONS: Addition of B to PC is associated with increased
      survival in previously untreated patients with nonsquamous NSCLC. Adenocarcinoma
      was associated with an increased survival benefit of PCB treatment. Data for
      other histologies are inconclusive, primarily because of small patient sample
      sizes and large CIs.

PMID- 20686430
TI  - Effects of a just-in-time educational intervention placed on wound dressing
      packages: a multicenter randomized controlled trial.
AB  - PURPOSE: I compared the effects of a just-in-time educational intervention
      (educational materials for dressing application attached to the manufacturer's
      dressing package) to traditional wound care education on reported confidence and
      dressing application in a simulated model. SUBJECTS AND SETTINGS: Nurses from a
      variety of backgrounds were recruited for this study. The nurses possessed all
      levels of education ranging from licensed practical nurse to master of science in
      nursing. Both novice and seasoned nurses were included, with no stipulations
      regarding years of nursing experience. Exclusion criteria included nurses who
      spent less than 50% of their time in direct patient care and nurses with advanced
      wound care training and/or certification (CWOCN, CWON). Study settings included
      community-based acute care facilities, critical access hospitals, long-term care
      facilities, long-term acute care facilities, and home care agencies. No level 1
      trauma centers were included in the study for geographical reasons. METHODS:
      Participants were randomly allocated to control or intervention groups. Each
      participant completed the Kent Dressing Confidence Assessment tool. Subjects were
      then asked to apply the dressing to a wound model under the observation of either
      the principal investigator or a trained observer, who scored the accuracy of
      dressing application according to established criteria. RESULTS: None of the 139
      nurses who received traditional dressing packaging were able to apply the
      dressing to a wound model correctly. In contrast, 88% of the nurses who received
      the package with the educational guide attached to it were able to apply the
      dressing to a wound model correctly (chi2 = 107.22, df = 1, P = .0001). Nurses
      who received the dressing package with the attached educational guide agreed that
      this feature gave them confidence to correctly apply the dressing (88%), while no
      nurse agreed that the traditional package gave him or her the confidence to apply
      the dressing correctly (chi2 = 147.47, df = 4, P < .0001). CONCLUSIONS: A just-in
      time education intervention improved nurses' confidence when applying an
      unfamiliar dressing and accuracy of application when applying the dressing to a
      simulated model compared to traditional wound care education.

PMID- 20686431
TI  - The contribution of hospital nursing leadership styles to 30-day patient
      mortality.
AB  - BACKGROUND: Nursing work environment characteristics, in particular nurse and
      physician staffing, have been linked to patient outcomes (adverse events and
      patient mortality). Researchers have stressed the need for nursing leadership to
      advance change in healthcare organizations to create safer practice environments
      for patients. The relationship between styles of nursing leadership in hospitals
      and patient outcomes has not been well examined. OBJECTIVE: The purpose of this
      study was to examine the contribution of hospital nursing leadership styles to 30
      day mortality after controlling for patient demographics, comorbidities, and
      hospital factors. METHODS: Ninety acute care hospitals in Alberta, Canada, were
      categorized into five styles of nursing leadership: high resonant, moderately
      resonant, mixed, moderately dissonant, and high dissonant. In the secondary
      analysis, existing data from three sources (nurses, patients, and institutions)
      were used to test a hypothesis that the styles of nursing leadership at the
      hospital level contribute to patient mortality rates. RESULTS: Thirty-day
      mortality was 7.8% in the study sample of 21,570 medical patients; rates varied
      across hospital categories: high resonant (5.2%), moderately resonant (7.4%),
      mixed (8.1%), moderately dissonant (8.8%), and high dissonant (4.3%). After
      controlling for patient demographics, comorbidities, and institutional and
      hospital nursing characteristics, nursing leadership styles explained 5.1% of
      72.2% of total variance in mortality across hospitals, and high-resonant
      leadership was related significantly to lower mortality. CONCLUSIONS: Hospital
      nursing leadership styles may contribute to 30-day mortality of patients. This
      relationship may be moderated by homogeneity of leadership styles, clarity of
      communication among leaders and healthcare providers, and work environment
      characteristics.

PMID- 20686432
TI  - Late pregnancy screening for human immunodeficiency virus.
AB  - Three cases are presented of infants born to mothers who were screened and tested
      negative for HIV during their first trimesters. None of these pregnant women were
      retested late in their pregnancies, as they were not considered at high risk for
      HIV infection. All were found to be infected shortly after giving birth. Of the 3
      infants, 2 developed HIV infection. These cases support a recommendation for late
      pregnancy HIV screening of all women.

PMID- 20686433
TI  - Association between nasopharyngeal load of Streptococcus pneumoniae, viral
      coinfection, and radiologically confirmed pneumonia in Vietnamese children.
AB  - BACKGROUND: The interplay between nasopharyngeal bacterial carriage, viral
      coinfection, and lower respiratory tract infections (LRTIs) is poorly understood.
      We explored this association in Vietnamese children aged less than 5 years.
      METHODS: A hospital-based case-control study of pediatric LRTIs was conducted in
      Nha Trang, Vietnam. A total of 550 hospitalized children (274 radiologically
      confirmed pneumonia [RCP] and 276 other LRTIs) were enrolled and 350 healthy
      controls were randomly selected from the community. Polymerase chain reaction
      based methods were used to measure bacterial loads of Streptococcus pneumoniae
      (SP), Haemophilus influenzae, and Moraxella catarrhalis and to detect 13
      respiratory viruses and bacterial serotypes in nasopharyngeal samples of study
      participants. RESULTS: The median nasopharyngeal bacterial load of SP was
      substantially higher in children with RCP compared with healthy controls or
      children with other LRTIs (P < 0.001). SP load was 15-fold higher in pneumonia
      children with viral coinfection compared with those children without viral
      coinfection (1.4 x 107/mL vs. 9.1 x 105/mL; P 0.0001). SP load was over 200-fold
      higher in serotypeable SP compared with nontypeable SP (2.5 x 106/mL vs. 1 x
      104/mL; P < 0.0001). These associations were independent of potential confounders
      in multiple regression models. No clear association was found between
      nasopharyngeal load of Haemophilus influenzae or Moraxella catarrhalis and viral
      coinfection in either RCP or other LRTIs groups. CONCLUSIONS: An increased load
      of SP in the nasopharynx was associated with RCP, viral coinfection, and presence
      of pneumococcal capsule.

PMID- 20686434
TI  - Adverse neurologic reactions after both doses of pandemic H1N1 influenza vaccine
      with optic neuritis and demyelination.
AB  - When a neurologic condition develops after vaccination of a patient, the causal
      relationship is difficult to determine. We report an unusual case in which
      neurologic signs occurred in a previously healthy child after both doses of H1N1
      2009 influenza vaccine, culminating in bilateral optic neuritis and disseminated
      encephalomyelitis. A causal association is more likely with repeated injury
      following influenza vaccination.

PMID- 20686435
TI  - Three children with plastic bronchitis associated with 2009 H1N1 influenza virus
      infection.
AB  - We report the cases of 3 children with plastic bronchitis associated with 2009
      H1N1 influenza virus infection. These 3 children shared common clinical and
      radiologic features: rapid and progressive respiratory distress with whole lung
      atelectasis on chest radiograph. In children with severe respiratory symptoms
      accompanied by H1N1 influenza, plastic bronchitis should be considered.

PMID- 20686436
TI  - Timing of the availability and administration of influenza vaccine through the
      vaccines for children program.
AB  - BACKGROUND: influenza vaccine must be distributed and administered each year
      during a limited time interval. To our knowledge, no previous studies have
      simultaneously evaluated the delivery and administration of privately purchased
      vaccines and influenza vaccines acquired through the Vaccines for Children (VFC)
      program. METHODS: a prospective, observational study was conducted in US
      outpatient pediatric offices, tracking all influenza vaccinations during the
      season by age group, first or second vaccination, the child's need for 1 or 2
      doses, type of vaccine, and VFC status. RESULTS: a total of 42 and 84 practices
      completed the study in 2007 to 2008 and 2008 to 2009, respectively. In both
      seasons, initial shipments of VFC influenza vaccine generally arrived 4 to 5
      weeks later than non-VFC shipments; VFC vaccine administration also started 1
      month later than administration of privately purchased vaccine. Vaccine
      administration peaked in early November and late October in years 1 and 2,
      respectively, and declined rapidly thereafter. Overall, approximately one-half of
      all children who required 2 doses of vaccine were estimated to have received 2
      doses. In both years, 2-dose compliance rates in the VFC population were 17% to
      19% lower than those in the non-VFC population, possibly resulting from the VFC
      population's shorter time interval for second dose receipt. CONCLUSIONS: the VFC
      program is critical to ensuring financially vulnerable children have access to
      vaccination. Manufacturers, distributors, and public health officials should
      deliver VFC influenza vaccine to providers as quickly as possible. Pediatric
      healthcare providers should increase efforts to vaccinate all populations,
      especially the VFC population, in later months.

PMID- 20686438
TI  - Outbreak of vim-1-carbapenemase-producing Enterobacter cloacae in a pediatric
      intensive care unit.
AB  - Pediatric patients are rarely infected with metallo-beta-lactamase-producing
      Enterobacteriaceae. We describe 3 cases of children infected with VIM-1-producing
      clonal Enterobacter cloacae. Patients were treated with amikacin and
      cotrimoxazole. The blaVIM-1 gene was carried into a class 1 integron and an
      IncHI2 incompatibility group plasmid. Emergence of pediatric infections caused by
      carbapenemases-producing Enterobacteriaceae is a critical issue as they are
      resistant to most beta-lactam antibiotics.

PMID- 20686439
TI  - Molecular and clinical characterization of rotavirus from diarrheal infants
      admitted to pediatric emergency units in france.
AB  - BACKGROUND: rotaviruses are the major cause of acute gastroenteritis in young
      children worldwide, and require careful surveillance, especially in the context
      of vaccination programs. Prospective surveillance is required to monitor and
      characterize rotavirus infections, including viral and clinical data, and to
      detect the emergence of potentially epidemic strains. METHODS: between 2006 and
      2009, stool samples and clinical records were collected from 2044 children with
      acute diarrhea admitted to the pediatric emergency units of 13 French university
      hospitals. Rotaviruses were detected in stools, then genotyped by reverse
      transcription-polymerase chain reaction with regard to their outer capsid
      proteins VP4 and VP7. RESULTS: the genotyping of 1947 rotaviruses showed that G1
      (61.7%) and G9 (27.4%) strains were predominant and stable, followed by G2
      (6.5%), G3 (4.0%), and G4 (2.5%) strains. Most strains were associated with P[8]
      (92.9%). Overall, 31 uncommon strains and possible zoonotic reassortants were
      detected including G12 and G8 strains, some being closely related to bovine
      strains. No difference in clinical presentation and severity was found among
      genotypes. CONCLUSIONS: the relative stability of rotavirus genotypes currently
      cocirculating in France may ensure vaccine effectiveness in the short and medium
      term. However, the likely emergence of G12 and G8 strains should be monitored
      during ongoing and future vaccination programs, especially as all genotypes can
      cause severe infections. Special attention should be paid to the emergence of new
      rotavirus reassortants not included in current rotavirus vaccines.

PMID- 20686440
TI  - Respiratory syncytial virus and Staphylococcus aureus coinfection in children
      hospitalized with pneumonia.
AB  - Respiratory syncytial virus (RSV) infection might facilitate bacterial infection.
      We describe 5 patients with RSV among 30 children admitted to pediatric hospitals
      in Atlanta between October 1, 2006 and April 30, 2007 with community-onset
      Staphylococcus aureus pneumonia. RSV-S. aureus patients were younger and had less
      medical comorbidity than those without RSV.

PMID- 20686437
TI  - Community-acquired respiratory infections in young children with congenital heart
      diseases in the palivizumab era: the Spanish 4-season civic epidemiologic study.
AB  - INTRODUCTION: To investigate the epidemiology of acute respiratory tract
      infections (ARIs) in children younger than 24 months old with hemodynamically
      significant congenital heart diseases. Primary aim: incidence of hospital
      admission due to ARI. Secondary aims: risk factors, etiologic agents, clinical
      outcomes, and usefulness of preventive measures. PATIENTS AND METHODS:
      Prospective, multicenter, epidemiologic study conducted in 57 Spanish hospitals
      covering four 7-month seasons (2004-2008). RESULTS: A total of 2613 patients were
      eligible for the study. Three hundred fifty-four patients (13.5%) (95% confidence
      interval: 12.3-14.9) required a total of 453 hospital admissions. Clinical
      diagnoses: bronchiolitis (54.1%), upper respiratory tract infection (21%),
      pneumonia (19.9%), and others (17.4%). Median length of hospital stay: 7.0 days.
      No etiologic agent was identified in two-thirds of the patients. In the remaining
      patients either a single agent (26.8%) or polymicrobial infection (5%) was
      identified. Respiratory syncytial virus (RSV) was the agent that was most
      commonly found (3.8% specific hospitalization rate). Children receiving adequate
      RSV prophylaxis (90.5%) had a 58.2% (95% confidence interval: 37.6-78.3)
      reduction in RSV hospitalization. Risk factors for admission included
      malnourishment, infant age, male gender, chromosome alterations, wheezing,
      inadequate RSV prophylaxis fulfillment, and siblings <11 years of age. Pediatric
      intensive care unit care was required in 21.8% of the admissions and 9 patients
      (0.34%) died. CONCLUSIONS: Hospital admission rate and severity of ARI remain as
      important issues in hemodynamically significant congenital heart disease
      patients. The strict fulfillment of prophylactic recommendations against RSV is
      the only protective factor that can be modulated to decrease the ARI hospital
      admission rate.

PMID- 20686441
TI  - Study of the therapeutic effects of proximal intercessory prayer (STEPP) on
      auditory and visual impairments in rural Mozambique.
AB  - BACKGROUND: Proximal intercessory prayer (PIP) is a common complementary and
      alternative medicine (CAM) therapy, but clinical effects are poorly understood,
      partly because studies have focused on distant intercessory prayer (DIP).
      METHODS: This prospective study used an audiometer (Earscan(R) 3) and vision
      charts (40 cm, 6 m "Illiterate E") to evaluate 24 consecutive Mozambican subjects
      (19 males/5 females) reporting impaired hearing (14) and/or vision (11) who
      subsequently received PIP interventions. RESULTS: We measured significant
      improvements in auditory (P <0.003) and visual (P <0.02) function across both
      tested populations. CONCLUSIONS: Rural Mozambican subjects exhibited improved
      audition and/or visual acuity subsequent to PIP. The magnitude of measured
      effects exceeds that reported in previous suggestion and hypnosis studies. Future
      study seems warranted to assess whether PIP may be a useful adjunct to standard
      medical care for certain patients with auditory and/or visual impairments,
      especially in contexts where access to conventional treatment is limited.

PMID- 20686442
TI  - The metabolic syndrome and new-onset diabetes after transplantation: presumed
      guilty?

PMID- 20686443
TI  - Chronic kidney disease in kidney transplant recipients-is it different from
      chronic native kidney disease?
AB  - BACKGROUND: The rate of change in estimated glomerular filtration rate
      (DeltaeGFR), factors influencing DeltaeGFR, and its association with mortality
      has not been well studied in renal transplant recipients. METHODS.: Adult kidney
      only recipients between January 2001 and December 2004, with surviving grafts 1
      year after transplantation, from England and Wales were followed up till 31
      December 2006, graft failure or death. The four variable modification of diet in
      renal disease equation was used to estimate GFR and DeltaeGFR assessed using
      linear least square regression. DeltaeGFR of -1 mL/min/1.73m per year and above
      was considered to be stable or improving function. Linear regression and Cox
      regression analyses were used to examine factors influencing DeltaeGFR and its
      association with mortality, respectively. RESULTS: Of the 2, 927 patients
      included, DeltaeGFR was -1.3+/-6.0 mL/min/1.73 m per year and eGFR remained
      stable or improved in the majority (54.8%). Baseline graft function at 1 year or
      live donor status did not influence DeltaeGFR. Male donor to female recipient
      transplantation, younger recipients, diabetes, white race, and human leukocyte
      antigen mismatch were associated with faster decline in eGFR. DeltaeGFR was not
      associated with mortality when censored for graft failure. CONCLUSIONS: Majority
      of renal transplant recipients experienced stable or improved graft function.
      Specific donor and recipient characteristics influenced the rate of decline in
      eGFR. The lack of association of DeltaeGFR with mortality, the stability of eGFR
      in the majority, and influence of donor characteristics on DeltaeGFR suggest
      caution when applying prognosis knowledge from the native kidney disease to the
      kidney transplant population.

PMID- 20686444
TI  - The significance of non-T-cell pathways in graft rejection: implications for
      transplant tolerance.
AB  - Both innate and adaptive immune cells are actively involved in the initiation and
      destruction of allotransplants, and there is a true need now to look beyond T
      cells in the allograft response, examining various non-T-cell types in transplant
      models and how such cell types interact with T cells in determining the fate of
      an allograft. Studies in this area may lead to further improvement in transplant
      outcomes.

PMID- 20686445
TI  - CCR2 antagonism improves insulin resistance, lipid metabolism, and diabetic
      nephropathy in type 2 diabetic mice.
AB  - Chemokine ligand 2 (CCL2) binds to its receptor C-C chemokine receptor 2 (CCR2),
      initiating tissue inflammation, and recent studies have suggested a beneficial
      effect of a blockade of this pathway in diabetic nephropathy. To investigate the
      mechanism of protection, we studied the effect of RS504393, a CCR2 antagonist, on
      insulin resistance and diabetic nephropathy in db/db mice. Administering this
      antagonist improved insulin resistance as confirmed by various biomarkers,
      including homeostasis model assessment index levels, plasma insulin levels, and
      lipid abnormalities. Mice treated with the antagonist had a significant decrease
      in epididymal fat mass as well as phenotypic changes of adipocytes into small
      differentiated forms with decreased CCL2 expression and lipid hydroperoxide
      levels. In addition, treatment with the CCR2 antagonist markedly decreased
      urinary albumin excretion, mesangial expansion, and suppressed profibrotic and
      proinflammatory cytokine synthesis. Furthermore, the CCR2 antagonist improved
      lipid metabolism, lipid hydroperoxide, cholesterol, and triglyceride contents of
      the kidney, and decreased urinary 8-isoprostane levels. Hence, our findings
      suggest that CCR2 antagonists can improve insulin resistance by modulation of the
      adipose tissue and restore renal function through both metabolic and anti
      fibrotic effects in type 2 diabetic mice.

PMID- 20686446
TI  - The role of Tregs and CD11c(+) macrophages/dendritic cells in ischemic
      preconditioning of the kidney.
AB  - Dendritic cells have the potential to induce tolerance and here we attempted to
      identify their role in the tolerance seen in ischemic pre-conditioning. We
      induced bilateral renal ischemic preconditioning in mice and then challenged them
      with an ischemic insult 7 days later. Compared to sham-operated controls,
      preconditioned mice were found to have reduced injury with less inflammation, but
      had an increased number of regulatory T cells (Tregs) in their kidneys after the
      delayed insult. Splenocytes from these mice had more Tregs and mature CD11c(+)
      cells, but reduced proliferative and cytokine-secretory responses, suggesting a
      state of immunosuppression compared to control mice. Anti-CD25 depletion followed
      by adoptive transfer of Tregs partially mitigated and then restored the
      protective effect of preconditioning. Depletion of CD11c(+) cells with liposomes
      containing clodronate was associated with partial loss of preconditioning
      benefits. The increased numbers of Tregs or impaired immune response found in
      splenocytes from preconditioned mice were partially reversed in splenocytes from
      liposome clodronate-treated animals, suggesting that CD11c(+) cells contribute to
      immune cell-mediated ischemic preconditioning. Hence, our results show that
      ischemic preconditioning of the kidney provides a negative signal to the
      peripheral immune system, partially mediating the tissue-protective and anti
      inflammatory effects of this maneuver.

PMID- 20686447
TI  - Bilirubin and biliverdin protect rodents against diabetic nephropathy by
      downregulating NAD(P)H oxidase.
AB  - We recently found a markedly lower prevalence of vascular complications,
      including kidney disease, in diabetic patients with Gilbert syndrome, a
      congenital form of hyperbilirubinemia, suggesting a beneficial effect of
      bilirubin (BIL) on diabetic nephropathy. To directly examine this, we determined
      whether hereditary hyperbilirubinemic Gunn j/j rats and biliverdin (BVD)-treated
      diabetic db/db mice were resistant to the development of renal disease. Both
      rodent models had less albuminuria and complete protection against the
      progression of mesangial expansion accompanied by normalization of transforming
      growth factor-beta1 and fibronectin expression. Simultaneously, there was
      normalization of urinary and renal oxidative stress markers, and the expression
      of nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase subunits in the
      kidney. In cultured vascular endothelial and mesangial cells, BIL and BVD
      significantly inhibited NADPH-dependent superoxide production, and both high
      glucose- and angiotensin II-induced production of reactive oxygen species.
      Collectively, our findings suggest that BIL and BVD may protect against diabetic
      nephropathy and may lead to novel antioxidant therapies for diabetic nephropathy.

PMID- 20686448
TI  - Sirolimus attenuates disease progression in an orthologous mouse model of human
      autosomal dominant polycystic kidney disease.
AB  - In autosomal dominant polycystic kidney disease (ADPKD), abnormal proliferation
      of tubular cells drives cyst development and growth. Sirolimus, an inhibitor of
      the protein kinase mammalian target of rapamycin (mTOR) and a potent anti
      proliferative agent, decreases cyst growth in several genetically distinct rodent
      models of polycystic kidney disease (PKD). We determined here the effect of
      sirolimus on renal cyst growth in Pkd2WS25/- mice; an ortholog of human ADPKD
      involving mutation of the Pkd2 gene. In Pkd2WS25/- mice treated with sirolimus,
      both the two kidney/total body weight (2K/TBW) ratio and the cyst volume density
      (CVD) were significantly decreased by over half compared with untreated mice
      suffering with PKD. However, there was no effect on the increased blood urea
      nitrogen (BUN) levels as an index of kidney function. There are two distinct
      complexes containing mTOR depending on its binding partners: mTORC1 and mTORC2.
      Western blot analysis of whole kidney lysates and immunohistochemistry of the
      cysts found that phospho-S6 ribosomal protein, a marker of mTORC1 activity, was
      increased in Pkd2WS25/- mice and its phosphorylation was decreased by sirolimus
      treatment. Phospho-Akt at serine 473, a marker associated with mTORC2 activity,
      was not different between Pkd2WS25/- mice and normal littermate controls. Hence,
      our study found that inhibition of mTORC1 by sirolimus correlated with decreased
      renal cyst growth in this model of human ADPKD but had no effect on the decline
      in renal function.

PMID- 20686450
TI  - Comparison of three methods for isolation of urinary microvesicles to identify
      biomarkers of nephrotic syndrome.
AB  - Urinary microvesicles, such as 40-100 nm exosomes and 100-1000 nm microparticles,
      contain many proteins that may serve as biomarkers of renal disease.
      Microvesicles have been isolated by ultracentrifugation or nanomembrane
      ultrafiltration from normal urine; however, little is known about the efficiency
      of these methods in isolating microvesicles from patients with nephrotic-range
      proteinuria. Here we compared three techniques to isolate microvesicles from
      nephrotic urine: nanomembrane ultrafiltration, ultracentrifugation, and
      ultracentrifugation followed by size-exclusion chromatography (UC-SEC). Highly
      abundant urinary proteins were still present in sufficient quantity after
      ultrafiltration or ultracentrifugation to blunt detection of less abundant
      microvesicular proteins by MALDI-TOF-TOF mass spectrometry. The microvesicular
      markers neprilysin, aquaporin-2, and podocalyxin were highly enriched following
      UC-SEC compared with preparations by ultrafiltration or ultracentrifugation
      alone. Electron microscopy of the UC-SEC fractions found microvesicles of varying
      size, compatible with the presence of both exosomes and microparticles. Thus, UC
      SEC following ultracentrifugation to further enrich and purify microparticles
      facilitates the search for prognostic biomarkers that might be used to predict
      the clinical course of nephrotic syndrome.

PMID- 20686449
TI  - Selective deletion of Connexin 40 in renin-producing cells impairs renal
      baroreceptor function and is associated with arterial hypertension.
AB  - Renin-producing juxtaglomerular cells are connected to each other and to
      endothelial cells of afferent arterioles by gap junctions containing Connexin 40
      (Cx40), abundantly expressed by these two cell types. Here, we generated mice
      with cell-specific deletion of Cx40 in endothelial and in renin-producing cells,
      as its global deletion caused local dissociation of renin-producing cells from
      endothelial cells, renin hypersecretion, and hypertension. In mice lacking
      endothelial Cx40, the blood pressure, renin-producing cell distribution, and the
      control of renin secretion were similar to wild-type mice. In contrast, mice
      deficient for Cx40 in renin-producing cells were hypertensive and these cells
      were ectopically localized. Although plasma renin activity and kidney renin mRNA
      levels of these mice were not different from controls, the negative regulation of
      renin secretion by pressure was inverted to a positive feedback in kidneys
      lacking Cx40 in renin-producing cells. Thus, our findings show that endothelial
      Cx40 is not essential for the control of renin expression and/or release. Cx40 in
      renin-producing cells is required for their correct positioning in the
      juxtaglomerular area and the control of renin secretion by pressure.

PMID- 20686451
TI  - Parathyroid Klotho and FGF-receptor 1 expression decline with renal function in
      hyperparathyroid patients with chronic kidney disease and kidney transplant
      recipients.
AB  - Current studies suggest that short-term exposure of parathyroid glands to
      fibroblast growth factor 23 (FGF23) reduces parathyroid hormone secretion.
      However, patients with chronic kidney disease (CKD) develop secondary
      hyperparathyroidism despite high levels of serum FGF23, indicating a parathyroid
      FGF23 'resistance'. Here we analyzed the expression of the FGF23 receptors Klotho
      and FGF receptor 1 (FGFR1) in 88 hyperplastic parathyroid glands from 31 patients
      with CKD (including 21 renal allograft recipients), and their regulation in
      isolated bovine and human hyperplastic parathyroid cells. Glandular expression
      was variable, yet the Klotho and FGFR1 mRNA levels declined in parallel with the
      decreasing glomerular filtration rate, significantly decreasing over CKD stages.
      We found no association between the expression of Klotho, FGFR1, and the
      proliferation marker Ki67. In vitro treatment of bovine cells with FGF23 or
      calcium reduced the Klotho level, whereas active vitamin D(3) compounds increased
      its expression. Phosphate and parathyroid hormone had no effect. Treatment had
      less impact on Klotho in cultured human cells than in the bovine healthy cell
      model, whereas FGFR1 expression was induced in the hyperplastic cells. Thus
      parathyroid Klotho and FGFR1 decrease with declining renal function, possibly
      because of alterations in mineral metabolism related to the failing kidney. This
      could explain the observed parathyroid resistance to FGF23 in late CKD.

PMID- 20686452
TI  - The duration of postoperative acute kidney injury is an additional parameter
      predicting long-term survival in diabetic veterans.
AB  - Acute kidney injury (AKI) is primarily defined and staged according to the
      magnitude of the rise in serum creatinine. Here we sought to determine if the
      duration of AKI adds additional prognostic information above that from the
      magnitude of injury alone. We prospectively studied 35,302 diabetic patients from
      123 Veterans Affairs Medical Centers undergoing their first noncardiac surgery.
      The main outcome was long-term mortality in those who survived the index
      hospitalization. AKI was stratified by magnitude according to AKI Network stages
      and by the duration (short (less than 2 days), medium (3-6 days) or long (7 days
      or more)). Overall, 17.8% of patients experienced at least stage 1 AKI or greater
      following surgery. Both the magnitude and duration of AKI were significantly
      associated with long-term survival in a dose-dependent manner. Within each stage,
      longer duration of AKI was significantly associated with a graded higher rate of
      mortality. However, within each of the duration categories, the stage was not
      associated with mortality. When considered separately in multivariate analyses,
      both a higher stage and duration were independently associated with increased
      risk of long-term mortality. Hence, the duration of AKI adds additional
      information to predict long-term mortality.

PMID- 20686453
TI  - Acute kidney injury following coronary angiography is associated with a long-term
      decline in kidney function.
AB  - To determine whether acute kidney injury results in later long-term decline in
      kidney function we measured changes in kidney function over a 3-year period in
      adults undergoing coronary angiography who had serum creatinine measurements as
      part of their clinical care. Acute kidney injury was categorized by the magnitude
      of increase in serum creatinine (mild (50-99% or >or=0.3 mg/dl) and moderate or
      severe (>or=100%)) within 7 days of coronary angiography. Compared to patients
      without acute kidney injury, the adjusted odds of a sustained decline in kidney
      function at 3 months following angiography increased more than 4-fold for
      patients with mild to more than 17-fold for those with moderate or severe acute
      kidney injury. Among those with an estimated glomerular filtration rate after
      angiography less than 90 ml/min per 1.73 m(2), the subsequent adjusted mean rate
      of decline in estimated glomerular filtration rate during long-term follow-up
      (all normalized to 1.73 m(2) per year) was 0.2 ml/min in patients without acute
      kidney injury, 0.8 ml/min following mild injury, and 2.8 ml/min following
      moderate to severe acute kidney injury. Thus, acute kidney injury following
      coronary angiography is associated with a sustained loss and a larger rate of
      future decline in kidney function.

PMID- 20686454
TI  - Peripheral BDNF produces antidepressant-like effects in cellular and behavioral
      models.
AB  - Recent clinical studies demonstrate that serum levels of brain-derived
      neurotrophic factor (BDNF) are significantly decreased in patients with major
      depressive disorder (MDD) and that antidepressant treatments reverse this effect,
      indicating that serum BDNF is a biomarker of MDD. These findings raise the
      possibility that serum BDNF may also have effects on neuronal activity and
      behavior, but the functional significance of altered serum BDNF is unknown. To
      address this issue, we determined the influence of peripheral BDNF administration
      on depression- and anxiety-like behavior, including the forced swim test (FST),
      chronic unpredictable stress (CUS)/anhedonia, novelty-induced hypophagia (NIH)
      test, and elevated-plus maze (EPM). Furthermore, we examined adult hippocampal
      neurogenesis as well as hippocampal and striatal expression of BDNF,
      extracellular signal-regulated kinase (ERK) and cAMP response element-binding
      protein (CREB), in order to determine whether peripherally administered BDNF
      produces antidepressant-like cellular responses in the brain. Peripheral BDNF
      administration increased mobility in the FST, attenuated the effects of CUS on
      sucrose consumption, decreased latency in the NIH test, and increased time spent
      in the open arms of an EPM. Moreover, adult hippocampal neurogenesis was
      increased after chronic, peripheral BDNF administration. We also found that BDNF
      levels as well as expression of pCREB and pERK were elevated in the hippocampus
      of adult mice receiving peripheral BDNF. Taken together, these results indicate
      that peripheral/serum BDNF may not only represent a biomarker of MDD, but also
      have functional consequences on molecular signaling substrates, neurogenesis, and
      behavior.

PMID- 20686456
TI  - Relapse prevention in schizophrenia and schizoaffective disorder with risperidone
      long-acting injectable vs quetiapine: results of a long-term, open-label,
      randomized clinical trial.
AB  - Chronic management of schizophrenia and schizoaffective disorders is frequently
      complicated by symptomatic relapse. An open-label, randomized, active-controlled,
      2-year trial evaluated 710 patients with schizophrenia or related disorders who
      were switched from stable treatment with oral risperidone, olanzapine, or
      conventional neuroleptics to risperidone long-acting injectable (RLAI) or oral
      quetiapine. Primary effectiveness evaluation was time-to-relapse. Safety
      evaluations included adverse events (AEs) reported for the duration of the study,
      Extrapyramidal Symptom Rating Scale (ESRS), clinical laboratory tests, and vital
      signs. A total of 666 patients (n=329 RLAI, n=337 quetiapine) were evaluable for
      effectiveness measures. Baseline demographics were similar between treatment
      groups. Kaplan-Meier estimate of time-to-relapse was significantly longer with
      RLAI (p<0.0001). Relapse occurred in 16.5% of patients with RLAI and 31.3% with
      quetiapine. RLAI and quetiapine were both safe and well tolerated. Weight gain
      affected 7% of patients with RLAI and 6% with quetiapine, with mean end point
      increases of 1.25+/-6.61 and 0+/-6.55 kg, respectively. There were no significant
      between-group differences in weight gain. ESRS total scores decreased similarly
      after randomization to either RLAI or quetiapine. Extrapyramidal AEs occurred in
      10% of patients with RLAI and 6% with quetiapine. Treatment-emergent potentially
      prolactin-related AEs were reported in 15 (5%) patients with RLAI and 5 (2%)
      patients with quetiapine; hyperprolactinemia was reported in 43 (13.1%) patients
      with RLAI and 5 (1.5%) patients with quetiapine. Somnolence occurred in 2% of
      patients with RLAI and 11% with quetiapine. To our knowledge, this is the first
      report of a randomized clinical trial directly comparing relapse prevention with
      a second-generation long-acting injectable antipsychotic and oral therapy. Time
      to-relapse in stable patients with schizophrenia or schizoaffective disorder was
      significantly longer in patients randomized to RLAI compared with those
      randomized to oral quetiapine. Both antipsychotics were generally well tolerated.

PMID- 20686458
TI  - Measuring quality of care in patients with nonvariceal upper gastrointestinal
      hemorrhage: development of an explicit quality indicator set.
AB  - OBJECTIVES: With an increasing emphasis on quality in health care and recognition
      of inconsistencies in the management of patients with nonvariceal upper
      gastrointestinal hemorrhage (NVUGIH), it is critical to establish a set of
      explicit quality indicators (QIs) in NVUGIH. METHODS: We conducted a nine-member,
      multidisciplinary expert panel and followed modified Delphi methods to
      systematically identify a set of QIs for NVUGIH. The panel performed independent
      ratings of each candidate QI using a nine-point RAND appropriateness scale, then
      met in person and re-voted using an iterative process of discussion. The final
      set comprised QIs with a median RAND Appropriateness Score >or=7 and no
      disagreement among experts. RESULTS: Among 116 candidate QIs, the panel rated 26
      as valid measures of quality care. The selected QIs cover pre-endoscopy,
      endoscopy, and post-endoscopy care, including diagnosis, early resuscitation,
      risk stratification, endoscopic care, Helicobacter pylori management, and proton
      pump inhibitor therapy. CONCLUSIONS: We have developed an explicit set of
      evidence-based QIs in NVUGIH, providing physicians and institutions with a tool
      to identify processes amenable to quality improvement. This tool is intended to
      be applicable in all institutions providing care for NVUGIH patients.

PMID- 20686455
TI  - Ventral striatal noradrenergic mechanisms contribute to sensorimotor gating
      deficits induced by amphetamine.
AB  - The psychotomimetic drug D-amphetamine (AMPH), disrupts prepulse inhibition (PPI)
      of the startle response, an operational measure of sensorimotor gating that is
      deficient in schizophrenia patients. Historically, this effect has been
      attributed to dopaminergic substrates; however, AMPH also increases
      norepinephrine (NE) levels, and enhancement of central NE transmission has been
      shown recently to disrupt PPI. This study examined the extent to which NE might
      participate in AMPH-induced disruptions of PPI and increases in locomotor
      activity, another classic behavioral effect of AMPH, by determining whether
      antagonism of postsynaptic NE receptors blocked these effects. Separate groups of
      male Sprague-Dawley rats received either the alpha1 receptor antagonist, prazosin
      (0, 0.3, 1 mg/kg), or the beta receptor antagonist timolol (0, 3, 10 mg/kg)
      before administration of AMPH (0 or 1 mg/kg) before testing for PPI or locomotor
      activity. As an initial exploration of the anatomical substrates underlying
      possible alpha1 receptor-mediated effects on AMPH-induced PPI deficits, the
      alpha1 receptor antagonist terazosin (0 or 40 MUg/0.5 MUl) was microinfused into
      the nucleus accumbens shell (NAccSh) in conjunction with systemic AMPH
      administration before startle testing in a separate experiment. Prazosin, but not
      timolol, blocked AMPH-induced hyperactivity; both drugs reversed AMPH-induced PPI
      deficits without altering baseline startle responses. Interestingly, AMPH-induced
      PPI deficits also were partially blocked by terazosin in NAccSh. Thus, behavioral
      sequelae of AMPH (PPI disruption and hyperactivity) may be mediated in part by NE
      receptors, with alpha1 receptors in NAccSh possibly having an important role in
      the sensorimotor gating deficits induced by this psychotomimetic drug.

PMID- 20686459
TI  - Length of office visits for gastrointestinal disease: impact of physician
      specialty.
AB  - OBJECTIVES: Physician-visit length is an important determinant of patient
      satisfaction and outcomes. Our objective was to compare visit length for
      gastrointestinal disorders between gastroenterologists and primary-care providers
      (PCPs). METHODS: From the National Ambulatory Medical Care Survey, visits to
      office-based physician practices between 1993 and 2004 were identified and
      multivariate regression was used to identify predictors of visit duration.
      RESULTS: There were 3135, 3391, and 3964 office visits associated with
      gastrointestinal disease, corresponding to 71, 140, and 180 million visits
      nationwide in 1993-1996, 1997-2000, and 2001-2004 respectively. Visit duration to
      all physicians increased from 17.3 minutes in 1993-1996 to 20.2 minutes in 2001
      2004. Among gastroenterologists, visit length remained constant, from 21.0
      minutes in 1993-1996 to 22.3 minutes in 2001-2004. On multivariate regression,
      age >50 years (1.8 minutes), new-patient encounters (7.4 minutes), and visits in
      1997-2000 (2.7 minutes) and 2001-2004 (3.4 minutes) were associated with longer
      visit length. Encounters with gastroenterologists (3.3 minutes) were associated
      with longer visit duration than those with PCPs. The greatest adjusted difference
      in visit length between the two was seen for visits associated with constipation
      (5.7 minutes favoring gastroenterologists) and irritable bowel syndrome (2.4
      minutes). CONCLUSIONS: There has been an overall increase in length of physician
      visits associated with gastrointestinal disease. Both patient and provider
      factors predict visit length.

PMID- 20686460
TI  - Lactose intolerance and the role of the lactose breath test.

PMID- 20686463
TI  - Peginterferon therapy for HBeAg-negative chronic hepatitis B: less than meets the
      eye.
AB  - Pegylated interferon (PEG IFN) has been recommended as a first-line therapy for
      hepatitis B e antigen (HBeAg)-negative chronic hepatitis B; however, data
      supporting this recommendation are derived from a single randomized controlled
      trial. In this issue of the Journal, Rijckborst et al. report the results of a
      second randomized controlled PEG IFN trial in 138 HBeAg-negative patients. The
      trial was undertaken to test the efficacy of adding ribavirin to PEG IFN;
      however, the results were unequivocal in concluding that adding ribavirin was not
      effective. Moreover, the efficacy of PEG IFN for these HBeAg-negative subjects
      was disappointing; only 7.5% of the study cohort had undetectable hepatitis B
      virus DNA (<400 copies/ml) 24 weeks after a 48-week course of therapy, and none
      lost hepatitis B surface antigen. This study challenges the value and limits the
      appeal of PEG IFN therapy for HBeAg-negative chronic hepatitis B.

PMID- 20686466
TI  - Inflammatory bowel disease, irritable bowel syndrome, or what?: A challenge to
      the functional-organic dichotomy.
AB  - Many patients with inflammatory bowel disease (IBD) in clinical remission
      continue to have symptoms of pain and diarrhea despite minimal or no ongoing
      inflammation. These patients may be considered to have an overlap of IBD and
      irritable bowel syndrome (IBD-IBS). In this month's Journal, a proposal is made
      that continued symptoms in patients with elevated calprotectin, a marker of
      inflammation, is related to IBD. We propose an alternate biopsychosocial model
      whereby mutual effects of peripheral and central factors influence symptom
      generation in both IBD and IBS. Understanding this model has important
      implications for treatment of patients with IBD-IBS.

PMID- 20686467
TI  - Administrative database studies in IBD: a cautionary tale.
AB  - The inflammatory bowel diseases (IBDs) have been extensively studied with
      administrative databases. Ananthakrishnan et al. (this issue) used an
      administrative database to develop a risk score that predicted disease severity
      in hospitalized Crohn's disease patients. To understand the implication of this
      work, the concept of risk adjustment is reviewed and the advantages and
      disadvantages of using administrative databases to study hospitalization outcomes
      in IBD patients are discussed.

PMID- 20686469
TI  - Is lumping peer-reviewed case reports together with non-peer-reviewed comments
      for publication as letters to the editor appropriate?

PMID- 20686470
TI  - The sensitivity of combined IgG4 and IgG in autoimmune pancreatitis.

PMID- 20686471
TI  - Causes of mortality related to peptic ulcer bleeding in a prospective cohort of
      965 French patients: a plea for primary prevention.

PMID- 20686472
TI  - A case of hereditary hemorrhagic telangiectasia associated with Crohn's disease
      successfully treated with infliximab.

PMID- 20686473
TI  - Dacryoadenitis, an extra-intestinal manifestation of Crohn's disease.

PMID- 20686474
TI  - Ileoanal pouch inlet obstruction following cesarean section.

PMID- 20686476
TI  - Antidotes and treatments for chemical warfare/terrorism agents: an evidence-based
      review.
AB  - This article reviews the evidence supporting the efficacy of antidotes used or
      recommended for the potential chemical warfare agents of most concern. Chemical
      warfare agents considered include cyanide, vesicants, pulmonary irritants such as
      chlorine and phosgene, and nerve agents. The strength of evidence for most
      antidotes is weak, highlighting the need for additional research in this area.

PMID- 20686477
TI  - Quantification of apixaban's therapeutic utility in prevention of venous
      thromboembolism: selection of phase III trial dose.
AB  - A model-based approach was used to integrate data from a phase II study in order
      to provide a quantitative rationale for selecting the apixaban dosage regimen for
      a phase III trial. The exposure-response models demonstrated that an increase in
      daily steady-state area under the plasma concentration-vs.-time curve (AUC(ss))
      of 1 microg x h/ml would increase the odds ratio for major bleeding by 0.118 and
      decrease the odds ratio for venous thromboembolism (VTE) by 0.0499. The
      therapeutic utility index (TUI) was used to integrate the efficacy and safety
      predictions to quantify apixaban's efficacy/safety balance as a function of
      AUC(ss). Of the apixaban dosage regimens tested in phase II, the 2.5 mg twice
      daily (b.i.d.) dosage regimen had the highest TUI (86.2%). This was also higher
      than the TUI for either 30 mg b.i.d. enoxaparin (82.5%) or for warfarin (71.8%).
      Subjects with moderate renal impairment are expected to have a 43% increase in
      apixaban exposure; however, apixaban's TUI suggests that dose adjustment is not
      needed in these subjects with renal impairment.

PMID- 20686478
TI  - Prescription drug abuse: insight into the epidemic.
AB  - The emergence of clinically efficacious prescription drugs to treat pain,
      anxiety, and learning disorders is accompanied by the potential for nonmedical
      use. Prescription drug abuse has become a modern-day epidemic in the United
      States and is now second only to marijuana use across all age groups. This
      article reviews the various data collection, analysis, and reporting systems that
      have been developed in response to the growing concern for nonmedical
      prescription drug use. The terminology used to categorize prescription drugs that
      are abused and the various definitions for abuse, misuse, and nonmedical use are
      discussed. The epidemiology of nonmedical prescription drug use and an overview
      of each class of prescription drug that is at risk for nonmedical use are
      presented along with details of specific drugs that are associated with
      significant morbidity or mortality.

PMID- 20686479
TI  - Antidotes for alcohol and glycol toxicity: translating mechanisms into
      treatments.
AB  - Translational toxicology can be defined as the movement of potential antidotes
      for the treatment of poisonings from basic mechanistic research to the
      marketplace. Because poisonings are infrequent, the clinical development of
      antidotes is fraught with trials and tribulations. Academic scientists often
      conduct basic mechanistic work with antidotes but are infrequently involved in
      further drug development. This article presents the development of 4
      methylpyrazole (4MP) (fomepizole) as an antidote against toxic alcohol
      poisonings, particularly by methanol and ethylene glycol (EG).

PMID- 20686480
TI  - Increased risk of adverse pregnancy outcomes in women receiving zolpidem during
      pregnancy.
AB  - This nationwide population-based study was carried out in Taiwan with the aim of
      comparing the risk of adverse pregnancy outcomes in women who received zolpidem
      treatment for insomnia during pregnancy with that in women who did not. The
      adverse outcomes identified and assessed were delivery of low-birth-weight (LBW)
      infants, preterm deliveries, delivery of small-for-gestational-age (SGA) infants,
      delivery of infants with congenital anomalies, and cesarean delivery. The
      incidences of these were compared between the groups after adjusting for other
      characteristics of the mothers and infants. The study used the Taiwan National
      Health Insurance Research Dataset (NHIRD) and birth-certificate registry. In
      total, the data from 2,497 mothers who received zolpidem treatment during
      pregnancy and those from 12,485 randomly selected mothers who did not receive the
      drug were included in the analysis. The results show that the adjusted odds
      ratios (ORs) for adverse pregnancy outcomes--LBW infants, preterm deliveries, SGA
      infants, and cesarean delivery--were all higher in mothers who received zolpidem
      treatment during pregnancy, relative to the randomly selected controls (1.39 (95%
      confidence interval (CI) = 1.17-1.64), 1.49 (95% CI = 1.28-1.74), 1.34 (95% CI =
      1.20-1.49), and 1.74 (95% CI = 1.59-1.90), respectively). In conclusion, the risk
      of adverse pregnancy outcomes was higher in women who received zolpidem during
      pregnancy than in those who did not.

PMID- 20686481
TI  - Rb regulates fate choice and lineage commitment in vivo.
AB  - Mutation of the retinoblastoma gene (RB1) tumour suppressor occurs in one-third
      of all human tumours and is particularly associated with retinoblastoma and
      osteosarcoma. Numerous functions have been ascribed to the product of the human
      RB1 gene, the retinoblastoma protein (pRb). The best known is pRb's ability to
      promote cell-cycle exit through inhibition of the E2F transcription factors and
      the transcriptional repression of genes encoding cell-cycle regulators. In
      addition, pRb has been shown in vitro to regulate several transcription factors
      that are master differentiation inducers. Depending on the differentiation factor
      and cellular context, pRb can either suppress or promote their transcriptional
      activity. For example, pRb binds to Runx2 and potentiates its ability to promote
      osteogenic differentiation in vitro. In contrast, pRb acts with E2F to suppress
      peroxisome proliferator-activated receptor gamma subunit (PPAR-gamma), the master
      activator of adipogenesis. Because osteoblasts and adipocytes can both arise from
      mesenchymal stem cells, these observations suggest that pRb might play a role in
      the choice between these two fates. However, so far, there is no evidence for
      this in vivo. Here we use mouse models to address this hypothesis in mesenchymal
      tissue development and tumorigenesis. Our data show that Rb status plays a key
      role in establishing fate choice between bone and brown adipose tissue in vivo.

PMID- 20686484
TI  - Hypertension impairs myocardial blood perfusion reserve in subjects without
      regional myocardial ischemia.
AB  - Quantitative analysis of myocardial perfusion MRI can provide noninvasive
      assessments of myocardial perfusion reserve (MPR), which is associated with
      endothelial function. Endothelial function is influenced by various factors,
      including hypertension, diabetes, dyslipidemia, renal dysfunction and anemia. The
      purpose of this study was to evaluate which risk factor is the strongest effector
      of MPR in subjects without regional myocardial ischemia. We studied 110 patients
      (66 years +/-10, male 68%, hypertension 76%, diabetes mellitus (DM) 40% and
      dyslipidemia 65%) without regional myocardial ischemia. Adenosine triphosphate
      (ATP) stress and rest first-pass perfusion magnetic resonance (MR) images were
      acquired with a 1.5-T MR system, and MPR was calculated as the ratio of stress to
      rest myocardial blood flow (MBF). Average rest MBF in 110 patients was 1.07+/
      0.62 ml min-1 g-1, whereas stress MBF was 3.15+/-1.93 ml min-1 g-1 and the MPR
      was 3.33+/-1.82. Rest MBF correlated significantly with hematocrit, whereas
      stress MBF showed a strong correlation with estimated glomerular filtration rate
      (e-GFR). MPR was associated with hypertension, age, e-GFR, hematocrit and left
      ventricular mass index (LVMI). In multiple regression analysis, hypertension
      (P=0.003, beta=-0.274) showed the strongest correlation with MPR among other risk
      factors, such as diabetes (P=ns), dyslipidemia (P=ns), e-GFR (P=ns), LVMI
      (P=0.007, beta=-0.248) and hematocrit (P=ns) after adjusting age and gender.
      Hypertension is the most important effector of MPR in subjects without myocardial
      ischemia.

PMID- 20686482
TI  - Type IIA topoisomerase inhibition by a new class of antibacterial agents.
AB  - Despite the success of genomics in identifying new essential bacterial genes,
      there is a lack of sustainable leads in antibacterial drug discovery to address
      increasing multidrug resistance. Type IIA topoisomerases cleave and religate DNA
      to regulate DNA topology and are a major class of antibacterial and anticancer
      drug targets, yet there is no well developed structural basis for understanding
      drug action. Here we report the 2.1 A crystal structure of a potent, new class,
      broad-spectrum antibacterial agent in complex with Staphylococcus aureus DNA
      gyrase and DNA, showing a new mode of inhibition that circumvents fluoroquinolone
      resistance in this clinically important drug target. The inhibitor 'bridges' the
      DNA and a transient non-catalytic pocket on the two-fold axis at the GyrA dimer
      interface, and is close to the active sites and fluoroquinolone binding sites. In
      the inhibitor complex the active site seems poised to cleave the DNA, with a
      single metal ion observed between the TOPRIM (topoisomerase/primase) domain and
      the scissile phosphate. This work provides new insights into the mechanism of
      topoisomerase action and a platform for structure-based drug design of a new
      class of antibacterial agents against a clinically proven, but conformationally
      flexible, enzyme class.

PMID- 20686485
TI  - The role of renal microvascular disease and interstitial inflammation in salt
      sensitive hypertension.
AB  - Primary (essential) hypertension has been shown to be mediated by a relative
      impairment in sodium excretion by the kidney, but the mechanisms responsible for
      this defect are still being clarified. Increasing evidence suggests a role for
      subtle acquired renal injury in mediating this process. Microvascular injury is
      present in the majority of subjects with hypertension. The development of
      arteriolosclerosis, primarily of the afferent arteriole, may interfere with
      glomerular autoregulation, whereas the loss of peritubular capillaries may
      facilitate local ischemia. These changes favor the localization of T cells and
      macrophages into the interstitium, which, coupled with local oxidative stress and
      angiotensin II generation, may contribute to the impaired pressure natriuresis
      observed with salt-sensitive hypertension. Consistent with this hypothesis,
      therapies that are aimed at blocking the immune response, including thymectomy,
      genetic alterations in mice resulting in impaired immune responses, or the use of
      immunosuppressive agents, can protect against the development of hypertension in
      experimental models. Preliminary data in humans also suggest that the inhibition
      of the renal inflammatory response may reduce blood pressure. The present
      investigations are directed to gain insight in the role of the intrarenal T-cell
      reactivity and autoimmunity in driving the tubulointerstitial inflammation and
      its participation in the pathogenesis of salt-sensitive hypertension.

PMID- 20686486
TI  - Effectiveness and safety of high-dose valsartan monotherapy in hypertension
      treatment: the ValTop study.
AB  - Early combination therapy is increasingly recommended in hypertension management
      because of increased risk of adverse effects with high-dose monotherapy. However,
      this risk is not necessarily increased for high doses of angiotensin receptor
      blockers (ARB). ValTop study compared efficacy and safety of high vs.
      conventional dose of valsartan in hypertensive patients. ValTop was a controlled,
      randomized, double-blind trial. Of 6035 screened subjects, 4004 mild-to-moderate
      hypertensive patients (mean seated diastolic blood pressure (MSDBP) 90-109 mm Hg)
      started 4-week open-label treatment with valsartan 160 mg. Of them, 3776 were
      randomized to receive valsartan 160 mg (N=1900) or 320 mg (N=1876) o.d. for 4
      weeks. In 28-week open-label extension study, all participating patients (N=642)
      received valsartan 320 mg. Valsartan 160 mg reduced MSDBP by 10.0 mm Hg in the
      initial open-label phase. Further BP reductions in the double-blind phase were
      significantly (P<0.0001) greater in the 320 mg group than in the 160 mg group for
      MSDBP (1.6 +/- 0.18 mm Hg vs. 0.5 +/- 0.18 mm Hg) and mean seated systolic BP
      (3.3 +/- 0.31 mm Hg vs. 0.7 +/- 0.31 mm Hg). The size of the additional effect of
      the 320 mg dose on BP was similar in subjects controlled or not by the initial
      160 mg dose. Adverse event (AE) rates were similar in both treatment groups, drug
      related AEs occurring in <5% of subjects in each phase. High-dose valsartan is
      safe and effective in uncomplicated mild-to-moderate hypertension independently
      of the initial response to a moderate dose. High-dose ARB monotherapy may thus be
      a viable option in hypertension management.

PMID- 20686487
TI  - Asymmetric features of short-term blood pressure variability.
AB  - Prolongations of cardiac cycles have a significantly larger contribution to short
      term heart rate variability than shortenings--this is called heart rate
      asymmetry. Our aim is to establish the existence of blood pressure asymmetry
      phenomenon, which has not been done so far. We used 30-min resting continuous
      recordings of finger pressure waveforms from 227 healthy young volunteers (19-31
      years old; 97 female), and performed Poincare plot analysis of systolic blood
      pressure (SBP) to quantify the effect. Median contribution of SBP increases
      (C(i)) to short-term blood pressure variability was 52.8% (inter-quartile range:
      50.9-55.1%) and median number of SBP increases (N(i)) was 48.8% (inter-quartile
      range: 47.2-50.1%). The C(i)>50% was found in 82% (P<0.0001; binomial test) and
      N(i)<50% in 75% (P<0.0001) of the subjects. Although SBP increases are
      significantly less abundant than reductions, their contribution to short-term
      blood pressure variability is significantly larger, which means that short-term
      blood pressure variability is asymmetric. SBP increases and reductions have
      unequal contribution to short-term blood pressure variability at supine rest in
      young healthy people. As this asymmetric behavior of blood pressure variability
      is present in most of the healthy studied people at rest, it can be concluded
      that blood pressure asymmetry is a physiological phenomenon.

PMID- 20686488
TI  - Glomerular angiotensinogen is induced in mesangial cells in diabetic rats via
      reactive oxygen species--ERK/JNK pathways.
AB  - Whereas intra-renal angiotensinogen is predominantly localized in proximal
      tubular cells under basal conditions, it has been previously reported that
      angiotensinogen expression is induced in glomeruli under pathological conditions.
      However, there is no detailed information regarding the mechanism of the induced
      glomerular angiotensinogen. We used genetic pairs of Zucker diabetic fatty (ZDF)
      obese and lean rats to determine glomerular angiotensinogen expression. The
      levels of glomerular angiotensinogen immunoreactivity in ZDF obese rats were
      higher than those in ZDF lean rats. Double staining by IHC or IF with
      angiotensinogen and Thy1.1 antibodies showed that the majority of angiotensinogen
      in glomeruli was seen in mesangial cells. The levels of glomerular
      immunoreactivity for 4-HNE and urinary excretion of 8-isoprostane-markers of ROS
      in ZDF obese rats were higher than those in ZDF lean rats. To confirm this
      system, primary rat mesangial cells were treated with hydrogen peroxide (H2O2) to
      clarify the signal transduction pathway for glomerular angiotensinogen
      expression. H2O2 induced an increase in angiotensinogen expression in a dose- and
      time-dependent manner, and the H2O2-induced upregulation of angiotensinogen was
      suppressed by catalase. Furthermore, the H2O2-induced upregulation of
      angiotensinogen was inhibited by a mitogen-activated protein kinase (MAPK) kinase
      (MEK) inhibitor and a c-Jun N-terminal kinase (JNK) inhibitor, but not inhibited
      by a p38 MAPK inhibitor. These data suggest that the majority of angiotensinogen
      was induced in mesangial cells in glomeruli under pathological conditions such as
      diabetic nephropathy, and angiotensinogen expression in mesangial cells was
      mediated by H2O2 and the subsequent activation of extracellular-regulated kinase
      (ERK)/JNK pathways.

PMID- 20686489
TI  - Accuracy of a single rigid conical cuff with standard-size bladder coupled to an
      automatic oscillometric device over a wide range of arm circumferences.
AB  - Although the upper arm has the shape of a truncated cone, cylindrical cuffs and
      bladders are currently used for blood pressure (BP) measurement. The aims of this
      study were to describe upper arm characteristics and to test the accuracy of a
      standard adult-size conical cuff coupled to an oscillometric device over a wide
      range of arm circumferences. Arm characteristics were studied in 142 subjects
      with arm circumferences ranging from 22 to 45 cm (study 1). In a subset of 33
      subjects with the same range of arm circumferences, a rigid conical cuff with
      standard-size bladder (12.6 * 24.0 cm) and a rigid cylindrical cuff (13.3 * 24.0
      cm), both coupled to a Microlife BP A100 device, were tested according to the
      requirements of the protocol of the European Society of Hypertension (ESH; study
      2). Study 1. In all subjects, upper-arm shape was tronco-conical with slant
      angles ranging from 89.5 degrees  to 82.2 degrees . In a multiple linear
      regression analysis, only arm circumference was an independent predictor of
      conicity (P<0.001). Study 2. The rigid conical cuff passed all three phases of
      the ESH protocol for systolic and diastolic BPs. Mean device-observer BP
      differences obtained with the conical cuff were unrelated to arm circumference.
      When the rigid cylindrical cuff was used, ESH criteria were not satisfied, and
      the cuff overestimated systolic BPs in subjects with large arms. BP can be
      measured accurately with the use of a standard-size rigid conical cuff coupled to
      a BP A100 device for a wide range of arm circumferences.

PMID- 20686490
TI  - Comparison of strict- and mild-blood pressure control in elderly hypertensive
      patients: a per-protocol analysis of JATOS.
AB  - We performed a per-protocol analysis of the Japanese Trial to Assess Optimal
      Systolic Blood Pressure in Elderly Hypertensive Patients (JATOS) to evaluate the
      optimal target blood pressure (BP) in elderly hypertensive patients. In JATOS,
      conducted in elderly (65-85 years) hypertensive patients treated with efonidipine
      hydrochloride, there were no differences between the strict-treatment group
      (systolic BP maintained at <140 mm Hg) and the mild-treatment group (systolic BP
      maintained at >=140 mm Hg and <160 mm Hg) in the incidence of primary end points
      (cardiovascular disease and renal failure) for 2 years. The present study
      analyzed data in subgroups of JATOS in which the average systolic BP was within
      the range of target values. The average BP levels achieved in the strict-target
      BP achieved subgroup (n=1191) and the mild-target BP achieved subgroup (n=1531)
      were 132.3/74.0 mm Hg and 146.6/78.3 mm Hg, respectively. The incidences of
      primary end points were similar between these subgroups (11.1/1000 patients per
      year and 13.2/1000 patients per year, respectively, P=0.502), and there were also
      no differences in the incidences of adverse events. The incidences of
      cardiovascular events in patients who failed to achieve their respective
      treatment goals, on the other hand, were significantly higher than in patients
      who achieved them. These results indicate that strict treatment for elderly
      hypertensive patients may have little effect in enhancing the suppression of the
      onset of cardiovascular events as compared with mild treatment, although patients
      who have difficulties in achieving treatment goals should be given more
      aggressive treatment as a high-risk population.

PMID- 20686491
TI  - Glutathione-S-transferase gene polymorphisms (GSTM1, GSTT1, GSTP1) and idiopathic
      male infertility: novel perspectives versus facts.

PMID- 20686492
TI  - Combined microdeletions and CHD7 mutation causing severe CHARGE/DiGeorge
      syndrome: clinical presentation and molecular investigation by array-CGH.
AB  - Phenotypic variation in CHARGE syndrome remains unexplained. A subcategory of
      CHARGE patients show overlapping phenotypic characteristics with DiGeorge
      syndrome (thymic hypo/aplasia, hypocalcemia, T-cell immunodeficiency). Very few
      have been tested or reported to carry a mutation of the CHD7 (chromodomain
      helicase DNA-binding domain) gene detected in two-thirds of CHARGE patients. In
      an attempt to explore the genetic background of a severe CHARGE/DiGeorge
      phenotype, we performed comparative genomic array hybridization in an infant
      carrier of a CHD7 mutation. The high-resolution comparative genomic array
      hybridization revealed interesting findings, including a deletion distal to the
      DiGeorge region and disruptions in other chromosomal regions of genes implicated
      in immunological and other functions possibly contributing to the patient's
      severe phenotype and early death.

PMID- 20686493
TI  - Increased sensitivity of histidinemic mice to UVB radiation suggests a crucial
      role of endogenous urocanic acid in photoprotection.
AB  - Urocanic acid (UCA) is produced by the enzyme histidase and accumulates in the
      stratum corneum of the epidermis. In this study, we investigated the
      photoprotective role of endogenous UCA in the murine skin using histidinemic
      mice, in which the gene encoding histidase is mutated. Histidase was detected by
      immunohistochemistry in the stratum granulosum and stratum corneum of the normal
      murine skin but not in the histidinemic skin. The UCA content of the stratum
      corneum and the UVB absorption capacity of aqueous extracts from the stratum
      corneum were significantly reduced in histidinemic mice as compared with wild
      type mice. When the shaved back skin of adult mice was irradiated with 250 mJ cm(
      2) UVB, histidinemic mice accumulated significantly more DNA damage in the form
      of cyclobutane pyrimidine dimers than did wild-type mice. Furthermore, UVB
      irradiation induced significantly higher levels of markers of apoptosis in the
      epidermis of histidinemic mice. Topical application of UCA reversed the UVB
      photosensitive phenotype of histidinemic mice and increased UVB photoprotection
      of wild-type mice. Taken together, these results provide strong evidence for an
      important contribution of endogenous UCA to the protection of the epidermis
      against the damaging effects of UVB radiation.

PMID- 20686494
TI  - Overexpression of the transcription factor Yin-Yang-1 suppresses differentiation
      of HaCaT cells in three-dimensional cell culture.
AB  - Yin-Yang-1 (YY1) is a member of the GLI-Kruppel family of transcription factors,
      and both YY1 mRNA and protein expression have been identified in a number of
      different tissues and cell types suggesting that it is expressed both
      constitutively and ubiquitously. In epidermal tissue, however, we reported
      previously that YY1 protein is expressed at high levels in undifferentiated basal
      keratinocytes and is downregulated during differentiation toward the suprabasal
      layers. This differential expression pattern during keratinocyte differentiation
      suggests that YY1 may have an important role in regulating keratinocyte
      differentiation. In this study, we examined the role of YY1 in differentiation of
      the human keratinocyte cell line HaCaT using air-liquid interface three
      dimensional culture. The constitutive overexpression of YY1 in HaCaT cells during
      air exposure-induced differentiation resulted in an undifferentiated phenotype,
      thickening of the stratified layers, suppression of differentiation marker
      expression, and retention of proliferative activity. These findings suggested
      that YY1 may have an important role in maintenance of the undifferentiated
      phenotype of keratinocytes in the basal epidermal layer, and that reduction of
      YY1 expression in the suprabasal layers may allow keratinocytes to differentiate
      and move toward the upper layers of the epidermis.

PMID- 20686495
TI  - Targeted nanoparticles deliver siRNA to melanoma.
AB  - Melanoma is a severe skin cancer that often leads to death. To examine the
      potential of small interfering RNA (siRNA) therapy for melanoma, we have
      developed anisamide-targeted nanoparticles that can systemically deliver siRNA
      into the cytoplasm of B16F10 murine melanoma cells, which express the sigma
      receptor. A c-Myc siRNA delivered by the targeted nanoparticles effectively
      suppressed c-Myc expression in the tumor and partially inhibited tumor growth.
      More significant tumor growth inhibition was observed with nanoparticles composed
      of N,N-distearyl-N-methyl-N-2-(N'-arginyl) aminoethyl ammonium chloride (DSAA), a
      guanidinium-containing cationic lipid, than with a commonly used cationic lipid,
      1,2-dioleoyl-3-trimethylammonium-propane (DOTAP). Three daily injections of c-Myc
      siRNA formulated in the targeted nanoparticles containing DSAA could impair tumor
      growth, and the ED(50) of c-Myc siRNA was about 0.55  mg  kg(-1). The targeted
      DSAA nanoparticles containing c-Myc siRNA sensitized B16F10 cells to paclitaxel
      (Taxol), resulting in a complete inhibition of tumor growth for 1 week.
      Treatments of c-Myc siRNA in the targeted nanoparticles containing DSAA also
      showed significant inhibition on the growth of MDA-MB-435 tumor. The enhanced
      anti-melanoma activity is probably related to the fact that DSAA, but not DOTAP,
      induced reactive oxygen species, triggered apoptosis, and downregulated
      antiapoptotic protein Bcl-2 in B16F10 melanoma cells. Thus, the targeted
      nanoparticles containing c-Myc siRNA may serve as an effective therapeutic agent
      for melanoma.

PMID- 20686496
TI  - Genetic variants in the 53BP1 gene and skin cancer risk.

PMID- 20686497
TI  - Hypoxia impairs skin myofibroblast differentiation and function.
AB  - Ischemic wounds are characterized by oxygen levels lower than that of healthy
      skin (hypoxia) and poor healing. To better understand the pathophysiology of
      impaired wound healing, we investigated how switching from high (21%) to low (2%)
      oxygen levels directly affects cultured skin myofibroblasts, essential cells for
      the normal wound repair process. Myofibroblast differentiation and function were
      assessed by quantifying alpha-smooth muscle actin expression and cell contraction
      in collagen gels and on wrinkling silicone substrates. Culture for 5 days at 2%
      oxygen is perceived as hypoxia and significantly reduced myofibroblast
      differentiation and contraction despite high levels of the profibrotic
      transforming growth factor-beta1. Analysis of alpha-smooth muscle actin
      expression on wrinkling substrates over time showed that reduced myofibroblast
      contraction preceded alpha-smooth muscle actin disassembly from stress fibers
      after switching from 21 to 2% oxygen. These effects were reversible by restoring
      high oxygen conditions and by applying mechanical stress. We suggest that
      mechanical challenge is a clinical relevant strategy to improve ischemic and
      chronic wound healing by supporting myofibroblast formation.

PMID- 20686498
TI  - Japanese-specific filaggrin gene mutations in Japanese patients suffering from
      atopic eczema and asthma.

PMID- 20686499
TI  - Efficacy and safety of olmesartan medoxomil plus amlodipine in age, gender and
      hypertension severity defined subgroups of hypertensive patients.
AB  - Effective antihypertensive therapy is crucial for preventing cardiovascular
      events; however, blood pressure (BP) control rates remain poor. The objective of
      this analysis was to determine the efficacy of olmesartan/amlodipine in age,
      severity and gender-based subgroups of patients with moderate-to-severe
      hypertension uncontrolled by amlodipine monotherapy. Patients with uncontrolled
      BP after 8 weeks' amlodipine 5 mg monotherapy (n=755) were randomized to continue
      amlodipine 5 mg or receive olmesartan (10-40 mg) plus amlodipine 5 mg for 8
      weeks. Patients whose BP remained suboptimal were up-titrated to
      olmesartan/amlodipine 20/5, 40/5 or 40/10 mg. Changes in BP and numbers of
      controlled patients were calculated separately to assess efficacy in patients
      aged <65 or >=65 years, in those with moderate or severe hypertension, and in
      males and females. The antihypertensive effects of olmesartan/amlodipine were
      similar in patients aged <65 and >=65 years of age. Compared with patients with
      moderate hypertension at baseline, those with severe hypertension tended to show
      higher decreases in BP, but achieved lower goal rates despite this. Females
      showed larger mean reductions in diastolic (1.61 mm Hg; P=0.003) and systolic BP
      (1.72 mm Hg; P=0.053) than males, independent of age and dose. This gender
      difference appeared to be higher and more consistent across dose groups for
      patients <50 years of age, but the difference in the pattern between both age
      groups was not statistically significant (P=0.1526). These results suggest that
      olmesartan/amlodipine is effective and safe in a wide range of patients,
      regardless of age or hypertension severity. Small differences in responsiveness
      between females and males may exist, which require further investigation.

PMID- 20686500
TI  - Ambulatory pulse pressure as a novel predictor for long-term prognosis in
      essential hypertensive patients.
AB  - The prognostic value of ambulatory blood pressure (BP) monitoring for long-term
      prognosis varies in recent studies. The study aimed to investigate the role of
      ambulatory BP parameters in mortality and cardiovascular (CV) events in
      hypertensive patients. A series of 412 participants (59.3 +/- 4.0 years) who
      received ambulatory BP monitoring for their fluctuated BP, either untreated or
      treated since 1995, were enroled. The mortality and CV events were obtained by
      follow-up and linked to the National Death Registry in Taiwan. There were 233
      untreated and 179 treated patients. The latter were older with more comorbidity
      when compared with the former. After follow-up for 8.5 +/- 1.7 years, both
      ambulatory systolic BP and pulse pressure (PP) could predict all-cause mortality,
      non-CV mortality, CV disease and stroke after adjusting for baseline covariates.
      However, only ambulatory PP could predict CV mortality and coronary heart
      disease. Ambulatory PP is better than ambulatory systolic BP, particularly in
      prediction of all-cause mortality. There was no predictive value of office BP in
      any outcome. In conclusion, ambulatory PP is a good predictor for long-term
      outcomes in hypertensive patients. The parameters of ambulatory rather than
      office BP could be applied for risk stratification either before or under
      antihypertensive treatment.

PMID- 20686501
TI  - Plasma renin responses to mental stress and carotid intima-media thickness in
      black Africans: the SABPA study.
AB  - The renin-angiotensin-aldosterone system can be activated by sympathetic nervous
      input and is thought to have an important role in the prevalence of hypertension
      and cardiovascular risk in black Africans. We examined (1) the association
      between plasma renin responses to mental stress and a marker of sub-clinical
      atherosclerosis; and (2) associations between resting renin and 24-h ambulatory
      blood pressure. Participants were 143 urbanized black African men and women (43.1
      +/- 7.7 years) drawn from a study of Sympathetic Activity and Ambulatory Blood
      Pressure in Africans (SABPA). After an overnight fast, participants completed the
      Stroop mental stress task. Blood samples were drawn during baseline and 10 min
      after the task to assess the concentration of active renin in plasma. Blood
      pressure assessments included continuous Finometer measures during the stress
      testing and 24-h ambulatory monitoring. Carotid intima-media thickness (CIMT) was
      measured using high-resolution ultrasound. Approximately 50% of the sample
      responded to the task with an increase in renin concentration. Multiple linear
      regression analysis revealed an association between the renin stress response and
      CIMT (beta = 0.024, 95% confidence interval, 0.004-0.043), after adjustment for
      conventional risk factors, blood pressure stress responses and basal levels of
      renin activity (R(2) for model = 0.37). In addition, resting renin was inversely
      associated with ambulatory blood pressure. In summary, heightened release of
      renin during a laboratory mental stressor was associated with a marker of sub
      clinical atherosclerosis; thus, it may be a potential mechanism in explaining the
      increased burden of cardiovascular disease in urbanized black Africans.

PMID- 20686502
TI  - Sex difference in blood pressure among South Asian diaspora in Europe and North
      America and the role of BMI: a meta-analysis.
AB  - It is unclear whether the sex difference that is known to occur in blood pressure
      (BP) is similar in some South Asian populations. This study presents a meta
      analysis of the sex difference in BP, hypertension and the role of body mass
      index (BMI) in South Asian diaspora compared with populations of European
      descent. We systematically searched for studies that reported BP and hypertension
      among South Asian descent populations living in Europe and North America.
      Weighted mean differences in BP and risk ratios (RR) for hypertension were
      calculated for men and women. We included 11 studies in this meta-analysis. In
      general, men had a higher BP and prevalence of hypertension than women, for
      example, systolic BP was higher in men than in women among the Indian (7.21 mm
      Hg, 95% confidence interval (CI): 4.46-9.95) and European populations (6.12 mm
      Hg, 95% CI: 4.45-7.80). The difference was less in the Pakistani population (4.00
      mm Hg, 95% CI: 2.65-5.36). The Bangladeshi population showed a comparatively
      small sex difference in systolic (2.93 mm Hg, 95% CI: 1.20-4.66) and diastolic BP
      (0.68 mm Hg, 95% CI: -1.76 to 3.12) and prevalence of hypertension (RR 1.28, 95%
      CI: 0.66-2.46). Sex differences in BMI for the South Asian populations were
      greater than those in Europeans. The Indian population had similar sex
      differences in BP and hypertension compared with Europeans, but Pakistani and
      Bangladeshi had smaller sex differences. Sex differences in BMI might relate to
      the blunted sex differences in BP in Pakistani and Bangladeshi populations.
      Further research should focus on factors that underlie this intriguing sex
      difference among South Asian populations.

PMID- 20686503
TI  - AML xenograft efficiency is significantly improved in NOD/SCID-IL2RG mice
      constitutively expressing human SCF, GM-CSF and IL-3.

PMID- 20686504
TI  - Leukemic fusion genes MLL/AF4 and AML1/MTG8 support leukemic self-renewal by
      controlling expression of the telomerase subunit TERT.
AB  - MLL/AF4 and AML/MTG8 represent two leukemic fusion genes, which are most
      frequently found in infant acute lymphoblastic leukemia (ALL) and acute myeloid
      leukemia (AML), respectively. We examined the influence of MLL/AF4 and AML1/MTG8
      fusion genes on the expression of TERT coding for the telomerase protein subunit,
      and subsequently telomerase activity in t(4;11)-positive ALL and t(8;21)-positive
      cell lines, respectively. MLL/AF4 suppression diminished telomerase activity and
      expression of TERT. Blocking pro-apoptotic caspase activation in conjunction with
      MLL/AF4 knockdown enhanced the inhibition of TERT gene expression, which suggests
      that MLL/AF4 depletion does not reduce TERT expression levels by inducing
      apoptosis. Knockdown of HOXA7, a direct transcriptional target of MLL/AF4 fusion
      gene, caused a reduction of telomerase and TERT to an extent similar to that
      observed with MLL/AF4 suppression. Chromatin immunoprecipitation of SEM cells,
      using ectopically expressed FLAG-tagged Hoxa7, indicates HOXA7 binding site in
      the TERT promoter region. Furthermore, suppression of the AML1/MTG8 fusion gene
      was associated with severely reduced clonogenicity, induction of replicative
      senescence, impaired TERT expression and accelerated telomere shortening. We thus
      present findings that show a mechanistic link between leukemic fusion proteins,
      essential for development and maintenance of leukemia, and telomerase, a key
      element of both normal and malignant self-renewal.

PMID- 20686505
TI  - HDAC inhibitors augment cytotoxic activity of rituximab by upregulating CD20
      expression on lymphoma cells.
AB  - Anti-CD20 antibody rituximab is now essential for the treatment of CD20-positive
      B-cell lymphomas. Decreased expression of CD20 is one of the major mechanisms
      underlying both innate and acquired resistance to rituximab. In this study, we
      show that histone deacetylase (HDAC) inhibitors augment the cytotoxic activity of
      rituximab by enhancing the surface expression of CD20 antigen on lymphoma cells.
      HDAC inhibitors, valproic acid (VPA) and romidepsin, increased CD20 expression at
      protein and mRNA levels in B-cell lymphoma cell lines with relatively low CD20
      expression levels. The VPA-mediated increase in CD20 expression occurred at 1 m,
      which is clinically achievable and safe, but insufficient for inducing cell
      death. Chromatin immunoprecipitation assays revealed that HDAC inhibitors
      transactivated the CD20 gene through promoter hyperacetylation and Sp1
      recruitment. HDAC inhibitors potentiated the activity of rituximab in complement
      dependent cytotoxic assays. In mouse lymphoma models, HDAC inhibitors enhanced
      CD20 expression along with histone hyperacetylation in transplanted cells, and
      acted synergistically with rituximab to retard their growth. The combination with
      HDAC inhibitors may serve as an effective strategy to overcome rituximab
      resistance in B-cell lymphomas.

PMID- 20686506
TI  - Mantle cell lymphoma salvage regimen: synergy between a reprogrammed oncolytic
      virus and two chemotherapeutics.
AB  - Measles virus (MV)-PNP H(blind)antiCD20 is a CD20-targeted and prodrug convertase
      armed MV that temporarily controls growth of lymphoma xenografts in severe
      combined immunodeficiency (SCID) mice in combination with fludarabine phosphate
      (fludarabine). Herein, we examine the replication of this targeted virus and of a
      vaccine-lineage MV in disease bulks and circulating cells from mantle cell
      lymphoma (MCL) patients, and show that only the targeted virus is specific for
      CD20-expressing cells. We then assessed the efficacy of different regimens of
      administration of this virus in combination with fludarabine and cyclophosphamide
      (CPA) in an MCL xenograft model. We show that CPA administration before the
      beginning of virus treatment enhances oncolytic efficacy, likely through
      temporary immunosuppression. An interval of 1 week between intravenous virus
      administration and fludarabine treatment further enhanced oncolysis, by
      synchronizing maximum prodrug convertase expression with fludarabine
      availability. Finally, three 23-day courses of triple sequential treatment with
      CPA, virus and fludarabine treatment resulted in complete regression of the
      xenografts. Secondary disease symptoms interfered with survival, but average
      survival times increased from 22 to 77 days. These studies document a
      reprogrammed oncolytic virus, consolidating the effects of two chemotherapeutics,
      a concept well suited for a phase I clinical trial for MCL patients for whom
      conventional therapies have failed.

PMID- 20686507
TI  - Comparison of oncolytic adenoviruses for selective eradication of oral cancer and
      pre-cancerous lesions.
AB  - Oncolytic adenoviruses are being investigated as potential anti-cancer agents.
      Selective lytic replication in cancer cells is essential for an effective and
      safe treatment. In this study, we compared 11 oncolytic adenoviruses in relevant
      cell cultures to assess their use for treating oral cancer and pre-cancerous
      lesions. We determined the cytotoxicity of oncolytic adenovirus infection and
      calculated selectivity indices for cytotoxicity to cancer cells compared with
      normal oral keratinocytes and fibroblasts. Keratinocytes were very sensitive to
      wild-type adenovirus serotype 5 (Ad5); 1- to 3-log more than head and neck
      squamous cell carcinoma (HNSCC) cells. The potencies of oncolytic adenoviruses to
      kill HNSCC cells within 7 days after infection ranged from approximately 10 times
      less potent to approximately 10 times more potent than Ad5. The selectivity
      indices determined on fibroblasts and keratinocytes differed markedly. Two
      oncolytic adenoviruses were more selective than Ad5 for HNSCC cells compared with
      fibroblasts; and five viruses showed selective replication on HNSCC cells
      compared with keratinocytes. Overall, CRAd-S.RGD with E1A driven by the survivin
      promoter and an infectivity-enhancing capsid modification showed the most
      favourable cytotoxicity pattern; being very potent in killing HNSCC cells, only
      slightly less effective than Ad5 in killing pre-neoplastic keratinocytes and the
      least toxic to normal keratinocytes.

PMID- 20686508
TI  - Hydrostatic isolated limb perfusion with adeno-associated virus vectors enhances
      correction of skeletal muscle in Pompe disease.
AB  - Glycogen storage disease type II (Pompe disease; MIM 232300) stems from the
      inherited deficiency of acid-alpha-glucosidase (GAA; acid maltase; EC 3.2.1.20),
      which primarily involves cardiac and skeletal muscles. We hypothesized that
      hydrostatic isolated limb perfusion (ILP) administration of an adeno-associated
      virus (AAV) vector containing a muscle-specific promoter could achieve relatively
      higher transgene expression in the hindlimb muscles of GAA-knockout (GAA-KO)
      mice, in comparison with intravenous (IV) administration. ILP administration of
      AAV2/8 vectors encoding alkaline phosphatase or human GAA-transduced skeletal
      muscles of the hindlimb widely, despite the relatively low number of vector
      particles administered (1 * 1011), and IV administration of an equivalent vector
      dose failed to transduce skeletal muscle detectably. Similarly, ILP
      administration of fewer vector particles of the AAV2/9 vector encoding human GAA
      (3 * 1010) transduced skeletal muscles of the hindlimb widely and significantly
      reduced glycogen content to, in comparison with IV administration. The only
      advantage for IV administration was moderately high-level transduction of cardiac
      muscle, which demonstrated compellingly that ILP administration sequestered
      vector particles within the perfused limb. Reduction of glycogen storage in the
      extensor digitorum longus demonstrated the potential advantage of ILP-mediated
      delivery of AAV vectors in Pompe disease, because type II myofibers are resistant
      to enzyme replacement therapy. Thus, ILP will enhance AAV transduction of
      multiple skeletal muscles while reducing the required dosages in terms of vector
      particle numbers.

PMID- 20686509
TI  - Multiple syntrophic interactions in a terephthalate-degrading methanogenic
      consortium.
AB  - Terephthalate (TA) is one of the top 50 chemicals produced worldwide. Its
      production results in a TA-containing wastewater that is treated by anaerobic
      processes through a poorly understood methanogenic syntrophy. Using metagenomics,
      we characterized the methanogenic consortium inside a hyper-mesophilic (that is,
      between mesophilic and thermophilic), TA-degrading bioreactor. We identified
      genes belonging to dominant Pelotomaculum species presumably involved in TA
      degradation through decarboxylation, dearomatization, and modified beta-oxidation
      to H(2)/CO(2) and acetate. These intermediates are converted to CH(4)/CO(2) by
      three novel hyper-mesophilic methanogens. Additional secondary syntrophic
      interactions were predicted in Thermotogae, Syntrophus and candidate phyla OP5
      and WWE1 populations. The OP5 encodes genes capable of anaerobic autotrophic
      butyrate production and Thermotogae, Syntrophus and WWE1 have the genetic
      potential to oxidize butyrate to CO(2)/H(2) and acetate. These observations
      suggest that the TA-degrading consortium consists of additional syntrophic
      interactions beyond the standard H(2)-producing syntroph-methanogen partnership
      that may serve to improve community stability.

PMID- 20686510
TI  - Salmonella transcriptional signature in Tetrahymena phagosomes and role of acid
      tolerance in passage through the protist.
AB  - Salmonella enterica Typhimurium remains undigested in the food vacuoles of the
      common protist, Tetrahymena. Contrary to its interaction with Acanthamoeba spp.,
      S. Typhimurium is not cytotoxic to Tetrahymena and is egested as viable cells in
      its fecal pellets. Through microarray gene expression profiling we investigated
      the factors in S. Typhimurium that are involved in its resistance to digestion by
      Tetrahymena. The transcriptome of S. Typhimurium in Tetrahymena phagosomes showed
      that 989 and 1282 genes were altered in expression compared with that in water
      and in LB culture medium, respectively. A great proportion of the upregulated
      genes have a role in anaerobic metabolism and the use of alternate electron
      acceptors. Many genes required for survival and replication within macrophages
      and human epithelial cells also had increased expression in Tetrahymena,
      including mgtC, one of the most highly induced genes in all three cells types. A
      DeltamgtC mutant of S. Typhimurium did not show decreased viability in
      Tetrahymena, but paradoxically, was egested at a higher cell density than the
      wild type. The expression of adiA and adiY, which are involved in arginine
      dependent acid resistance, also was increased in the protozoan phagosome. A
      DeltaadiAY mutant had lower viability after passage through Tetrahymena, and a
      higher proportion of S. Typhimurium wild-type cells within pellets remained
      viable after exposure to pH 3.4 as compared with uningested cells. Our results
      provide evidence that acid resistance has a role in the resistance of Salmonella
      to digestion by Tetrahymena and that passage through the protist confers
      physiological advantages relevant to its contamination cycle.

PMID- 20686511
TI  - Function-specific response to depletion of microbial diversity.
AB  - Recent meta-analyses suggest that ecosystem functioning increases with
      biodiversity, but contradictory results have been presented for some microbial
      functions. Moreover, observations of only one function underestimate the
      functional role of diversity because of species-specific trade-offs in the
      ability to carry out different functions. We examined multiple functions in batch
      cultures of natural freshwater bacterial communities with different richness,
      achieved by a dilution-to-extinction approach. Community composition was assessed
      by molecular fingerprinting of 16S rRNA and chitinase genes, representing the
      total community and a trait characteristic for a functional group, respectively.
      Richness was positively related to abundance and biomass, negatively correlated
      to cell volumes and unrelated to maximum intrinsic growth rate. The response of
      chitin and cellulose degradation rates depended on the presence of a single
      phylotype. We suggest that species identity and community composition rather than
      richness matters for specific microbial processes.

PMID- 20686512
TI  - Analysis of human and animal fecal microbiota for microbial source tracking.
AB  - Microbial compositions of human and animal feces from South Korea were analyzed
      and characterized. In total, 38 fecal samples (14 healthy adult humans, 6
      chickens, 6 cows, 6 pigs and 6 geese) were analyzed by 454 pyrosequencing of the
      V2 region of the 16S rRNA gene. Four major phyla, Actinobacteria, Proteobacteria,
      Firmicutes and Bacteroidetes, were identified in the samples. Principal
      coordinate analysis suggested that microbiota from the same host species
      generally clustered, with the exception of those from humans, which exhibited
      sample-specific compositions. A network-based analysis revealed that several
      operational taxonomic units (OTUs), such as Lactobacillus sp., Clostridium sp.
      and Prevotella sp., were commonly identified in all fecal sources. Other OTUs
      were present only in fecal samples from a single organism. For example, Yania sp.
      and Bifidobacterium sp. were identified specifically in chicken and human fecal
      samples, respectively. These specific OTUs or their respective biological markers
      could be useful for identifying the sources of fecal contamination in water by
      microbial source tracking.

PMID- 20686513
TI  - Dominant and diet-responsive groups of bacteria within the human colonic
      microbiota.
AB  - The populations of dominant species within the human colonic microbiota can
      potentially be modified by dietary intake with consequences for health. Here we
      examined the influence of precisely controlled diets in 14 overweight men.
      Volunteers were provided successively with a control diet, diets high in
      resistant starch (RS) or non-starch polysaccharides (NSPs) and a reduced
      carbohydrate weight loss (WL) diet, over 10 weeks. Analysis of 16S rRNA sequences
      in stool samples of six volunteers detected 320 phylotypes (defined at >98%
      identity) of which 26, including 19 cultured species, each accounted for >1% of
      sequences. Although samples clustered more strongly by individual than by diet,
      time courses obtained by targeted qPCR revealed that 'blooms' in specific
      bacterial groups occurred rapidly after a dietary change. These were rapidly
      reversed by the subsequent diet. Relatives of Ruminococcus bromii (R-ruminococci)
      increased in most volunteers on the RS diet, accounting for a mean of 17% of
      total bacteria compared with 3.8% on the NSP diet, whereas the uncultured
      Oscillibacter group increased on the RS and WL diets. Relatives of Eubacterium
      rectale increased on RS (to mean 10.1%) but decreased, along with Collinsella
      aerofaciens, on WL. Inter-individual variation was marked, however, with >60% of
      RS remaining unfermented in two volunteers on the RS diet, compared to <4% in the
      other 12 volunteers; these two individuals also showed low numbers of R
      ruminococci (<1%). Dietary non-digestible carbohydrate can produce marked changes
      in the gut microbiota, but these depend on the initial composition of an
      individual's gut microbiota.

PMID- 20686514
TI  - Identity of epibiotic bacteria on symbiontid euglenozoans in O2-depleted marine
      sediments: evidence for symbiont and host co-evolution.
AB  - A distinct subgroup of euglenozoans, referred to as the 'Symbiontida,' has been
      described from oxygen-depleted and sulfidic marine environments. By definition,
      all members of this group carry epibionts that are intimately associated with
      underlying mitochondrion-derived organelles beneath the surface of the hosts. We
      have used molecular phylogenetic and ultrastructural evidence to identify the rod
      shaped epibionts of the two members of this group, Calkinsia aureus and B.bacati,
      hand-picked from the sediments of two separate oxygen-depleted, sulfidic
      environments. We identify their epibionts as closely related sulfur or sulfide
      oxidizing members of the epsilon proteobacteria. The epsilon proteobacteria
      generally have a significant role in deep-sea habitats as primary colonizers,
      primary producers and/or in symbiotic associations. The epibionts likely fulfill
      a role in detoxifying the immediate surrounding environment for these two
      different hosts. The nearly identical rod-shaped epibionts on these two
      symbiontid hosts provides evidence for a co-evolutionary history between these
      two sets of partners. This hypothesis is supported by congruent tree topologies
      inferred from 18S and 16S rDNA from the hosts and bacterial epibionts,
      respectively. The eukaryotic hosts likely serve as a motile substrate that
      delivers the epibionts to the ideal locations with respect to the oxic/anoxic
      interface, whereby their growth rates can be maximized, perhaps also allowing the
      host to cultivate a food source. Because symbiontid isolates and additional small
      subunit rDNA gene sequences from this clade have now been recovered from many
      locations worldwide, the Symbiontida are likely more widespread and diverse than
      presently known.

PMID- 20686515
TI  - Intracisternal or intrathecal glycine, taurine, or muscimol inhibit bicuculline
      induced allodynia and thermal hyperalgesia in mice.
AB  - AIM: To investigate the effects of GABA and glycine on analgesia in the central
      nervous system. METHODS: Glycine, taurine, or muscimol was injected with
      bicuculline into the cistern magna or the lumbar subarachnoidal space in ICR
      mice. The effects on bicuculline-induced allodynia in a touch-evoked agitation
      test and on pain threshold index in a hot-plate test were assessed. RESULTS: The
      dosages of the amino acids administered with bicuculline had no effect on motor
      behavior in conscious mice. Glycine or muscimol reduced bicuculline-induced
      allodynia regardless of the administration site, whereas intrathecal taurine
      reduced bicuculline-induced allodynia. Glycine, taurine, and muscimol all
      antagonized the effects induced by bicuculline in the hot-plate test, regardless
      of the administration site. CONCLUSION: Glycine, taurine, and muscimol were found
      to have anti-allodynic and anti-thermal hyperalgesic properties in vivo. These
      observations suggest an interaction between glycine and GABA receptors during the
      regulation of antinociception.

PMID- 20686516
TI  - State-dependent blockade of human ether-a-go-go-related gene (hERG) K(+) channels
      by changrolin in stably transfected HEK293 cells.
AB  - AIM: To study the effect of changrolin on the K(+) channels encoded by the human
      ether-a-go-go-related gene (hERG). METHODS: hERG channels were heterologously
      stably expressed in human embryonic kidney 293 cells, and the hERG K(+) currents
      were recorded using a standard whole-cell patch-clamp technique. RESULTS:
      Changrolin inhibited hERG channels in a concentration-dependent and reversible
      manner (IC(50)=18.23 mumol/L, 95% CI: 9.27-35.9 mumol/L; Hill coefficient=
      0.9446). In addition, changrolin shifted the activation curve of hERG channels by
      14.3+/-1.5 mV to more negative potentials (P<0.01, n=9) but did not significantly
      affect the steady-state inactivation of hERG (n=5, P>0.05). The relative block of
      hERG channels by changrolin was close to zero at the time point of channel
      opening by the depolarizing voltage step and quickly increased afterwards. The
      maximal block was achieved in the inactivated state, with no further development
      of the open channel block. In the "envelope of tails" experiments, the time
      constants of activation were found to be 287.8+/-46.2 ms and 174.2+/-18.4 ms,
      respectively, for the absence and presence of 30 mumol/L changrolin (P<0.05,
      n=7). The onset of inactivation was accelerated significantly by changrolin
      between -40 mV and +60 mV (P<0.05, n=7). CONCLUSION: The results demonstrate that
      changrolin is a potent hERG blocker that preferentially binds to hERG channels in
      the open and inactivated states.

PMID- 20686517
TI  - Magnesium lithospermate B extracted from Salvia miltiorrhiza elevates
      intracellular Ca(2+) level in SH-SY5Y cells.
AB  - AIM: To examine if magnesium lithospermate B (MLB), a potent inhibitor of
      Na(+)/K(+)-ATPase, leads to the elevation of intracellular Ca(2+) level as
      observed in cells treated with cardiac glycosides. METHODS: Viability of SH-SY5Y
      neuroblastoma cells treated with various concentrations of ouabain or MLB was
      measured. Intracellular Ca(2+) levels were visualized using Fluo4-AM (fluorescent
      dye) when cells were treated with ouabain or MLB in the presence or absence of KB
      R7943 (Na(+)/Ca(2+) exchanger inhibitor) and 2-APB (IP(3) receptor antagonist).
      Molecular modeling was conducted for the docking of ouabain or MLB to Na(+)/K(+)
      ATPase. Changes of cell body and dendrite morphology were monitored under a
      microscope. RESULTS: severe toxicity was observed in cells treated with ouabain
      of concentration higher than 1 micromol/L for 24 h while no apparent toxicity was
      observed in those treated with MLB. Intracellular Ca(2+) levels were
      substantially elevated by MLB (1 micromol/L) and ouabain (1 micromol/L) in
      similar patterns, and significantly reduced in the presence of KB-R7943 (10
      micromol/L) or 2-APB (100 micromol/L). Equivalent interaction with the binding
      cavity of Na(+)/K(+)-ATPase was simulated for ouabain and MLB by forming five
      hydrogen bonds, respectively. Treatment of ouabain (1 micromol/L), but not MLB (1
      mumol/L), induced dendritic shrink of SH-SY5Y cells. CONCLUSION: Comparable to
      ouabain, MLB leads to the elevation of intracellular Ca(2+) level presumably via
      the same mechanism by inhibiting Na(+)/K(+)-ATPase. The elevated Ca(2+) levels
      seem to be supplied by Ca(2+) influx through the reversed mode of the
      Na(+)/Ca(2+) exchanger and intracellular release from endoplasmic reticulum.

PMID- 20686518
TI  - Differential regulations of blood pressure and perturbed metabolism by total
      ginsenosides and conventional antihypertensive agents in spontaneously
      hypertensive rats.
AB  - AIM: To investigate the regulatory effects of total ginsenosides and the
      conventional antihypertensive agents (captopril, amlodipine, terazosin and
      hydrochlorothiazide) on the blood pressure and perturbed metabolism in
      spontaneously hypertensive rats (SHRs) and to analyze the cause-effect
      relationships between high blood pressure and the metabolic disorders of
      hypertension. METHODS: SHRs were administrated with total ginsenosides or the
      antihypertensive agents for eight weeks. Systolic blood pressure (SP) was
      measured every week and low-molecular-weight compounds in blood plasma were
      quantitatively analyzed using a nontargeted high-throughput metabolomic tool: gas
      chromatography/time of flight mass spectrometry (GC/TOFMS) . The metabolic
      patterns were evaluated using principal components analysis and potential markers
      of hypertension were identified. RESULTS: Total ginsenosides and the
      antihypertensive agents differentially regulated SP and the metabolic pattern in
      SHRs. Total ginsenosides caused a progressive and prolonged reduction of SP and
      markedly normalized the perturbed metabolism with 14 of 27 (51.8%) markers of
      hypertension which were regulated toward normal. Total ginsenosides also reduced
      free fatty acids' level toward normal levels. In contrast, captopril, amlodipine
      and terazosin efficiently depressed SP, but had little effect on metabolic
      perturbation with only 8 (29.6%), 4 (14.8%), and 4 (14.8%) markers, respectively,
      which were regulated. CONCLUSION: The metabolic changes persisted when the blood
      pressure was lowered by the conventional antihypertensive agents, suggesting that
      hypertension may not be the cause of the metabolic perturbation in SHRs.

PMID- 20686519
TI  - The features of reserpine-induced gastric mucosal lesions.
AB  - AIM: To reinvestigate the characteristics of reserpine-induced gastric mucosal
      lesions (GMLs). METHODS: The GML-inducing effect of reserpine and the time-course
      of recovery from reserpine-induced GMLs were examined in Sprague-Dawley (SD)
      rats. The GML-inducing and blood pressure-decreasing effects of Compound
      Hypotensive Tablets (CHTs) were investigated in spontaneously hypertensive rats
      (SHRs). Intracerebroventricular (icv) injection and vagotomy were performed to
      verify the central vagal mechanism in reserpine-induced GMLs. RESULTS: Single
      intraperitoneal (ip) injections of reserpine (0.25, 0.5, 1, 2, 4, and 6 mg/kg)
      dose-dependently induced GMLs in SD rats. Both single and repeated (2 weeks) oral
      administrations of reserpine led to slight GMLs at doses of 24 mg/kg and 10
      mg/kg, respectively. Blood pressure was significantly decreased in SHRs after 2
      months of CHT administration (0.01 and 0.03 mg/kg; doses were expressed as the
      amount of reserpine in the CHT). CHT doses of 0.3 mg/kg induced GMLs, but 0.1
      mg/kg did not. Examining the time course of recovery from GMLs, severe GMLs
      occurred 18 h after ip reserpine (4 mg/kg), obviously lessened at 1 week and
      healed spontaneously at 3 weeks. Intracerebroventricular injections of reserpine
      caused GMLs at much lower doses (0.08 and 0.4 mg/kg), and reserpine-induced GMLs
      were greatly inhibited by vagotomy, suggesting the involvement of a central vagal
      mechanism. CONCLUSION: Reserpine-induced GMLs were dose-dependent, and the
      lesions healed spontaneously within 3 weeks. Long-term treatment with CHT at
      doses adequate to decrease blood pressure will not induce GMLs. A central vagal
      mechanism was involved in reserpine-induced GMLs.

PMID- 20686520
TI  - Geniposide inhibits high glucose-induced cell adhesion through the NF-kappaB
      signaling pathway in human umbilical vein endothelial cells.
AB  - AIM: To investigate whether geniposide, an iridoid glucoside extracted from
      gardenia jasminoides ellis fruits, inhibits cell adhesion to human umbilical vein
      endothelial cells (HUVECs) induced by high glucose and its underlying mechanisms.
      METHODS: HUVECs were isolated from human umbilical cords and cultured. The
      adhesion of monocytes to HUVECs was determined using fluorescence-labeled
      monocytes. The mRNA and protein levels of vascular cell adhesion molecule-1 (VCAM
      1) and endothelial selectin (E-selectin) were measured using real-time RT-PCR and
      ELISA. Reactive oxygen species (ROS) production was measured using a fluorescent
      probe. The amounts of nuclear factor-kappa B (NF-kappaB) and inhibitory factor of
      NF-kappaB (IkappaB) were determined using Western blot analysis. The
      translocation of NF-kappaB from the cytoplasm to the nucleus was determined using
      immunofluorescence. RESULTS: Geniposide (10-20 mumol/L) inhibited high glucose
      (33 mmol/L)-induced adhesion of monocytes to HUVECs in a dose-dependent manner.
      This compound (5-40 mumol/L) also inhibited high glucose-induced expression of
      VCAM-1 and E-selectin at the gene and protein levels. Furthermore, geniposide (5
      20 micromol/L) decreased ROS production and prevented IkappaB degradation in the
      cytoplasm and NF-kappaB translocation from the cytoplasm to the nucleus in
      HUVECs. CONCLUSION: Geniposide inhibits the adhesion of monocytes to HUVECs and
      the expression of CAMs induced by high glucose, suggesting that the compound may
      represent a new treatment for diabetic vascular injury. The mechanism underlying
      this inhibitory effect may be related to the inhibition of ROS overproduction and
      NF-kappaB signaling pathway activation by geniposide.

PMID- 20686521
TI  - Inhibition of tumors cell growth in osteosarcoma-bearing SD rats through a
      combination of conventional and metronomic scheduling of neoadjuvant
      chemotherapy.
AB  - AIM: To investigate whether a combination of conventional and metronomic
      scheduling of chemotherapy could enhance and extend the effectiveness of
      chemotherapy against osteosarcoma. METHODS: A total of 110 osteosarcoma-bearing
      SD rats were randomly divided into four groups, three of which were given
      conventional, metronomic or combination scheduling of chemotherapy, and the
      remaining one served as a control. Tumor volumes were measured every week during
      the treatment period of 8 weeks. At the end of treatment, tumors were removed
      from the rats and weighed. Expression of VEGFA in tumors was determined using
      Western blot assays. RESULTS: As indicated by the tumor volume, conventional and
      metronomic schedules showed similar trends in tumor growth curves, and both of
      them lost their inhibitory effect in the sixth week, whereas the combination
      schedule maintained effectiveness until the end of treatment. Statistical
      significance with tumor volumes and weights was found among the groups (P<0.001),
      with combination scheduling being the most effective (P<0.001). Western blot
      indicated that all the therapy groups had significantly decreased expression of
      VEGFA (P<0.01), and the combination scheduling group had the lowest VEGFA
      expression. CONCLUSION: Combination of conventional and metronomic scheduling of
      chemotherapy could be a promising treatment for osteosarcoma. Antiangiogenesis
      contributed to the effect of combination scheduling.

PMID- 20686523
TI  - A sensitive indirect competitive enzyme-linked immunosorbent assay for the
      detection of sarsasapogenin in rat plasma.
AB  - AIM: To generate a polyclonal antibody against sarsasapogenin and to develop an
      indirect competitive enzyme-linked immunosorbent assay (IC-ELISA) method for the
      pharmacokinetic study of Sarsasapogenin in rats. METHODS: The antigen of
      sarsasapogenin was produced using an active ester method and subsequently used
      for raising polyclonal antibodies in rabbits. The specificity and sensitivity of
      the antibody were measured by IC-ELISA. Using the ELISA method, sarsasapogenin
      levels were measured in the serum of rats after an oral dose of 100 mg/kg.
      RESULTS: Polyclonal antibodies raised against sarsasapogenin-bovine serum albumin
      were generated and showed a high reactivity to sarsasapogenin. The antibodies
      exhibited minor cross-reactivity to ruscogenin (23%), diosgenin (22%), 25 (R, S)
      ruscogenin l-O-[beta-D-glucopyranosyl (1-->2)][beta-D-xylopyranosyl (1-->3)]-beta
      D-fucopyranoside (26%) and no cross-reactivity to diammonium glycyrrhizinate and
      notoginseng R1. The detection range of sarsasapogenin by this ELISA method was
      approximately 2.4-760 ng/mL. The recovery rates of 10 ng/mL, 100 ng/mL, and 500
      ng/mL were in the range of 91.0%-96.2% for intra-assay and 89.0%-92.0% for inter
      assay. The coefficients of variation (CV%) for intra- and inter-assays at the
      three different sarsasapogenin levels were 3.1%-8.3% (n=6) and 6.0%-14.1% (n=6),
      respectively. CONCLUSION: The IC-ELISA method is a sensitive test for the
      determination of sarsasapogenin concentration in rat plasma and for
      pharmacokinetic (PK) studies.

PMID- 20686522
TI  - Polymorphisms in the HOXD4 gene are not associated with peak bone mineral density
      in Chinese nuclear families.
AB  - AIM: To determine the associations between HOXD4 gene polymorphisms with peak
      bone mineral density (BMD) throughing measuring three tagging single nucleotide
      polymorphisms (tagSNPs), including rs1867863, rs13418078, and rs4972504, in
      HOXD4. METHODS: Four hundred Chinese nuclear families with male offspring (1215
      subjects) and 401 Chinese nuclear families with female offspring (1260 subjects)
      were recruited. BMD of the lumbar spine 1-4 (L1-4) and left proximal femur
      including total hip and femoral neck were measured by dual-energy X-ray
      absorptiometry. The quantitative transmission disequilibrium test (QTDT) was
      performed to investigate the association among the tagging SNPs, haplotypes and
      peak BMD. RESULTS: Only the CC genotype was identified in rs13418078 in the
      Chinese population, unlike other populations. We failed to find significant
      within-family association among these SNPs, haplotypes and peak BMD at any bone
      site in either male- or female-offspring nuclear families. CONCLUSION: The
      results suggest that genetic polymorphisms in HOXD4 may not be a major
      contributor to the observed variability in peak BMD in the lumbar spine and the
      hip in Chinese men and women.

PMID- 20686524
TI  - Novel vehicle based on cubosomes for ophthalmic delivery of flurbiprofen with low
      irritancy and high bioavailability.
AB  - AIM: To develop a novel vehicle based on cubosomes as an ophthalmic drug delivery
      system for flurbiprofen (FB) to reduce ocular irritancy and improve
      bioavailability. METHODS: FB-loaded cubosomes were prepared using hot and high
      pressure homogenization. Cubosomes were then characterized by particle size, zeta
      potential, encapsulation efficiency, particle morphology, inner cubic structure
      and in vitro release. Corneal permeation was evaluated using modified Franz-type
      cells. Ocular irritation was then evaluated using both the Draize method and
      histological examination. The ocular pharmacokinetics of FB was determined using
      microdialysis. RESULTS: The particle size of each cubosome formulation was about
      150 nm. A bicontinuous cubic phase of cubic P-type was determined using cryo
      transmission electron microscopy (cryo-TEM) observation and small angle X-ray
      scattering (SAXS) analysis. In vitro corneal permeation study revealed that FB
      formulated in cubosomes exhibited 2.5-fold (F1) and 2.0-fold (F2) increase in
      P(app) compared with FB PBS. In the ocular irritation test, irritation scores for
      each group were less than 2, indicating that all formulations exhibited excellent
      ocular tolerance. Histological examination revealed that neither the structure
      nor the integrity of the cornea was visibly affected after incubation with FB
      cubosomes. The AUC of FB administered as FB cubosome F2 was 486.36+/-38.93 ng.mL(
      1).min.microg(-1), which was significantly higher than that of FB Na eye drops
      (P<0.01). Compared with FB Na eye drops, the T(max) of FB cubosome F2 was about
      1.6-fold higher and the MRT was also significantly longer (P<0.001). CONCLUSION:
      This novel low-irritant vehicle based on cubosomes might be a promising system
      for effective ocular drug delivery.

PMID- 20686526
TI  - Slow progress.

PMID- 20686527
TI  - Domestic science.

PMID- 20686525
TI  - Discovery of novel PTP1B inhibitors with antihyperglycemic activity.
AB  - AIM: To discover and optimize a series of novel PTP1B inhibitors containing a
      thiazolidinone-substituted biphenyl scaffold and to further evaluate the
      inhibitory effects of these compounds in vitro and in vivo. METHODS: A total of
      36 thiazolidinone substituted biphenyl scaffold derivatives were prepared. An in
      vitro biological evaluation was done by Enzyme-based assay. The in vivo efficacy
      of 7Fb as an antihyperglycemic agent was evaluated in a BKS db/db diabetic mouse
      model with a dose of 50 mg.kg(-1).d(-1) for 4 weeks. RESULTS: The in vitro
      biological evaluation showed that compounds 7Fb and 7Fc could increase the
      insulin-induced tyrosine phosphorylation of IRbeta in CHO/hIR cells. In in vivo
      experiments, compound 7Fb significantly lowered the postprandial blood glucose,
      from 29.4+/-1.2 mmol/L with the vehicle to 24.7+/-0.6 mmol/L (P<0.01), and the
      fasting blood glucose from 27.3+/-1.5 mmol/L with the vehicle to 23.6+/-1.2
      mmol/L (P<0.05). CONCLUSION: A novel series of compounds were discovered to be
      PTP1B inhibitors. Among them, compound 7Fb significantly lowered the postprandial
      and fasting glucose levels, and the blood glucose level declined more rapidly
      than in metformin-treated mice. Thus, 7Fb may be a potential lead compound for
      developing new agents for the treatment of type II diabetes.

PMID- 20686533
TI  - Journal club. A conservation biologist considers the role of nature reserves in a
      warming world.

PMID- 20686540
TI  - Sponge genome goes deep.

PMID- 20686539
TI  - Demand for malaria drug soars.

PMID- 20686541
TI  - UK embryo agency faces the axe.

PMID- 20686542
TI  - 'Tough' chief to defend MRC.

PMID- 20686543
TI  - Salamander's egg surprise.

PMID- 20686544
TI  - Drug safety crackdown revs up.

PMID- 20686545
TI  - US report pins down future biosecurity.

PMID- 20686546
TI  - Deepwater Horizon: A scientist at the centre of the spill.

PMID- 20686547
TI  - Citizen science: People power.

PMID- 20686548
TI  - World view: Not by experts alone.

PMID- 20686550
TI  - UK coalition's funding plan accelerates trends Labour started.

PMID- 20686551
TI  - Harnessing telecoms cables for science.

PMID- 20686556
TI  - Earth science: An inner core slip-sliding away.

PMID- 20686557
TI  - Ecology: Close relatives are bad news.

PMID- 20686558
TI  - Crohn's disease: Genes, viruses and microbes.

PMID- 20686559
TI  - Spectroscopy: Attosecond prints of electrons.

PMID- 20686560
TI  - Neuroanatomy: From fin to forelimb.

PMID- 20686561
TI  - Metabolism: Malaria parasite stands out.

PMID- 20686562
TI  - Genomics: Variations in blood lipids.

PMID- 20686563
TI  - Inorganic chemistry: Cation o' nine tails.

PMID- 20686564
TI  - Obituary: Harry Whittington (1916-2010).

PMID- 20686566
TI  - From noncoding variant to phenotype via SORT1 at the 1p13 cholesterol locus.
AB  - Recent genome-wide association studies (GWASs) have identified a locus on
      chromosome 1p13 strongly associated with both plasma low-density lipoprotein
      cholesterol (LDL-C) and myocardial infarction (MI) in humans. Here we show
      through a series of studies in human cohorts and human-derived hepatocytes that a
      common noncoding polymorphism at the 1p13 locus, rs12740374, creates a C/EBP
      (CCAAT/enhancer binding protein) transcription factor binding site and alters the
      hepatic expression of the SORT1 gene. With small interfering RNA (siRNA)
      knockdown and viral overexpression in mouse liver, we demonstrate that Sort1
      alters plasma LDL-C and very low-density lipoprotein (VLDL) particle levels by
      modulating hepatic VLDL secretion. Thus, we provide functional evidence for a
      novel regulatory pathway for lipoprotein metabolism and suggest that modulation
      of this pathway may alter risk for MI in humans. We also demonstrate that common
      noncoding DNA variants identified by GWASs can directly contribute to clinical
      phenotypes.

PMID- 20686567
TI  - The Amphimedon queenslandica genome and the evolution of animal complexity.
AB  - Sponges are an ancient group of animals that diverged from other metazoans over
      600 million years ago. Here we present the draft genome sequence of Amphimedon
      queenslandica, a demosponge from the Great Barrier Reef, and show that it is
      remarkably similar to other animal genomes in content, structure and
      organization. Comparative analysis enabled by the sequencing of the sponge genome
      reveals genomic events linked to the origin and early evolution of animals,
      including the appearance, expansion and diversification of pan-metazoan
      transcription factor, signalling pathway and structural genes. This diverse
      'toolkit' of genes correlates with critical aspects of all metazoan body plans,
      and comprises cell cycle control and growth, development, somatic- and germ-cell
      specification, cell adhesion, innate immunity and allorecognition. Notably, many
      of the genes associated with the emergence of animals are also implicated in
      cancer, which arises from defects in basic processes associated with metazoan
      multicellularity.

PMID- 20686568
TI  - A ground-layer adaptive optics system with multiple laser guide stars.
AB  - To determine the influence of the environment on star formation, we need to study
      the process in the extreme conditions of massive young star clusters (
      approximately 10(4) solar masses) near the centre of our own Galaxy. Observations
      must be carried out in the near infrared because of very high extinction in
      visible light within the Galactic plane. We need high resolution to identify
      cluster members from their peculiar motions, and because most such clusters span
      more than 1', efficient observation demands a wide field of view. There is at
      present no space-based facility that meets all these criteria. Ground-based
      telescopes can in principle make such observations when fitted with ground-layer
      adaptive optics (GLAO), which removes the optical aberration caused by
      atmospheric turbulence up to an altitude of approximately 500 m (refs 7-10). A
      GLAO system that uses multiple laser guide stars has been developed at the 6.5-m
      MMT telescope, in Arizona. In previous tests, the system improved the resolution
      of the telescope by 30-50%, limited by wavefront error in the optics, but that
      was insufficient to allow rapid determination of cluster membership. Here we
      report observations of the core of the globular cluster M3 made after
      commissioning a sensor to monitor and remove slowly varying aberration in the
      optics. In natural seeing of 0.7'', the point spread function at 2.2-mum
      wavelength was sharpened uniformly to 0.3'' over a field of at least 2'. The wide
      field resolution was enhanced by a factor of two to three over previous work,
      with better uniformity, and extends to a wavelength of 1.2 mum. Entire stellar
      clusters may be examined in a single pointing, and cluster membership can be
      determined from two such observations separated by just one year.

PMID- 20686565
TI  - Biological, clinical and population relevance of 95 loci for blood lipids.
AB  - Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol,
      high-density lipoprotein cholesterol and triglycerides are among the most
      important risk factors for coronary artery disease (CAD) and are targets for
      therapeutic intervention. We screened the genome for common variants associated
      with plasma lipids in >100,000 individuals of European ancestry. Here we report
      95 significantly associated loci (P < 5 x 10(-8)), with 59 showing genome-wide
      significant association with lipid traits for the first time. The newly reported
      associations include single nucleotide polymorphisms (SNPs) near known lipid
      regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci
      not previously implicated in lipoprotein metabolism. The 95 loci contribute not
      only to normal variation in lipid traits but also to extreme lipid phenotypes and
      have an impact on lipid traits in three non-European populations (East Asians,
      South Asians and African Americans). Our results identify several novel loci
      associated with plasma lipids that are also associated with CAD. Finally, we
      validated three of the novel genes-GALNT2, PPP1R3B and TTC39B-with experiments in
      mouse models. Taken together, our findings provide the foundation to develop a
      broader biological understanding of lipoprotein metabolism and to identify new
      therapeutic opportunities for the prevention of CAD.

PMID- 20686569
TI  - Quantum entanglement between an optical photon and a solid-state spin qubit.
AB  - Quantum entanglement is among the most fascinating aspects of quantum theory.
      Entangled optical photons are now widely used for fundamental tests of quantum
      mechanics and applications such as quantum cryptography. Several recent
      experiments demonstrated entanglement of optical photons with trapped ions, atoms
      and atomic ensembles, which are then used to connect remote long-term memory
      nodes in distributed quantum networks. Here we realize quantum entanglement
      between the polarization of a single optical photon and a solid-state qubit
      associated with the single electronic spin of a nitrogen vacancy centre in
      diamond. Our experimental entanglement verification uses the quantum eraser
      technique, and demonstrates that a high degree of control over interactions
      between a solid-state qubit and the quantum light field can be achieved. The
      reported entanglement source can be used in studies of fundamental quantum
      phenomena and provides a key building block for the solid-state realization of
      quantum optical networks.

PMID- 20686570
TI  - Loss-free and active optical negative-index metamaterials.
AB  - The recently emerged fields of metamaterials and transformation optics promise a
      family of exciting applications such as invisibility, optical imaging with deeply
      subwavelength resolution and nanophotonics with the potential for much faster
      information processing. The possibility of creating optical negative-index
      metamaterials (NIMs) using nanostructured metal-dielectric composites has
      triggered intense basic and applied research over the past several years.
      However, the performance of all NIM applications is significantly limited by the
      inherent and strong energy dissipation in metals, especially in the near-infrared
      and visible wavelength ranges. Generally the losses are orders of magnitude too
      large for the proposed applications, and the reduction of losses with optimized
      designs seems to be out of reach. One way of addressing this issue is to
      incorporate gain media into NIM designs. However, whether NIMs with low loss can
      be achieved has been the subject of theoretical debate. Here we experimentally
      demonstrate that the incorporation of gain material in the high-local-field areas
      of a metamaterial makes it possible to fabricate an extremely low-loss and active
      optical NIM. The original loss-limited negative refractive index and the figure
      of merit (FOM) of the device have been drastically improved with loss
      compensation in the visible wavelength range between 722 and 738 nm. In this
      range, the NIM becomes active such that the sum of the light intensities in
      transmission and reflection exceeds the intensity of the incident beam. At a
      wavelength of 737 nm, the negative refractive index improves from -0.66 to -1.017
      and the FOM increases from 1 to 26. At 738 nm, the FOM is expected to become
      macroscopically large, of the order of 10(6). This study demonstrates the
      possibility of fabricating an optical negative-index metamaterial that is not
      limited by the inherent loss in its metal constituent.

PMID- 20686571
TI  - Real-time observation of valence electron motion.
AB  - The superposition of quantum states drives motion on the atomic and subatomic
      scales, with the energy spacing of the states dictating the speed of the motion.
      In the case of electrons residing in the outer (valence) shells of atoms and
      molecules which are separated by electronvolt energies, this means that valence
      electron motion occurs on a subfemtosecond to few-femtosecond timescale (1 fs =
      10(-15) s). In the absence of complete measurements, the motion can be
      characterized in terms of a complex quantity, the density matrix. Here we report
      an attosecond pump-probe measurement of the density matrix of valence electrons
      in atomic krypton ions. We generate the ions with a controlled few-cycle laser
      field and then probe them through the spectrally resolved absorption of an
      attosecond extreme-ultraviolet pulse, which allows us to observe in real time the
      subfemtosecond motion of valence electrons over a multifemtosecond time span. We
      are able to completely characterize the quantum mechanical electron motion and
      determine its degree of coherence in the specimen of the ensemble. Although the
      present study uses a simple, prototypical open system, attosecond transient
      absorption spectroscopy should be applicable to molecules and solid-state
      materials to reveal the elementary electron motions that control physical,
      chemical and biological properties and processes.

PMID- 20686572
TI  - Melting-induced stratification above the Earth's inner core due to convective
      translation.
AB  - In addition to its global North-South anisotropy, there are two other enigmatic
      seismological observations related to the Earth's inner core: asymmetry between
      its eastern and western hemispheres and the presence of a layer of reduced
      seismic velocity at the base of the outer core. This 250-km-thick layer has been
      interpreted as a stably stratified region of reduced composition in light
      elements. Here we show that this layer can be generated by simultaneous
      crystallization and melting at the surface of the inner core, and that a
      translational mode of thermal convection in the inner core can produce enough
      melting and crystallization on each hemisphere respectively for the dense layer
      to develop. The dynamical model we propose introduces a clear asymmetry between a
      melting and a crystallizing hemisphere which forms a basis for also explaining
      the East-West asymmetry. The present translation rate is found to be typically
      100 million years for the inner core to be entirely renewed, which is one to two
      orders of magnitude faster than the growth rate of the inner core's radius. The
      resulting strong asymmetry of buoyancy flux caused by light elements is
      anticipated to have an impact on the dynamics of the outer core and on the
      geodynamo.

PMID- 20686573
TI  - The evolution of mammal-like crocodyliforms in the Cretaceous Period of Gondwana.
AB  - Fossil crocodyliforms discovered in recent years have revealed a level of
      morphological and ecological diversity not exhibited by extant members of the
      group. This diversity is particularly notable among taxa of the Cretaceous Period
      (144-65 million years ago) recovered from former Gondwanan landmasses. Here we
      report the discovery of a new species of Cretaceous notosuchian crocodyliform
      from the Rukwa Rift Basin of southwestern Tanzania. This small-bodied form
      deviates significantly from more typical crocodyliform craniodental morphologies,
      having a short, broad skull, robust lower jaw, and a dentition with relatively
      few teeth that nonetheless show marked heterodonty. The presence of
      morphologically complex, complementary upper and lower molariform teeth suggests
      a degree of crown-crown contact during jaw adduction that is unmatched among
      known crocodyliforms, paralleling the level of occlusal complexity seen in
      mammals and their extinct relatives. The presence of another small-bodied mammal
      like crocodyliform in the Cretaceous of Gondwana indicates that notosuchians
      probably filled niches and inhabited ecomorphospace that were otherwise occupied
      by mammals on northern continents.

PMID- 20686574
TI  - Predicting protein structures with a multiplayer online game.
AB  - People exert large amounts of problem-solving effort playing computer games.
      Simple image- and text-recognition tasks have been successfully 'crowd-sourced'
      through games, but it is not clear if more complex scientific problems can be
      solved with human-directed computing. Protein structure prediction is one such
      problem: locating the biologically relevant native conformation of a protein is a
      formidable computational challenge given the very large size of the search space.
      Here we describe Foldit, a multiplayer online game that engages non-scientists in
      solving hard prediction problems. Foldit players interact with protein structures
      using direct manipulation tools and user-friendly versions of algorithms from the
      Rosetta structure prediction methodology, while they compete and collaborate to
      optimize the computed energy. We show that top-ranked Foldit players excel at
      solving challenging structure refinement problems in which substantial backbone
      rearrangements are necessary to achieve the burial of hydrophobic residues.
      Players working collaboratively develop a rich assortment of new strategies and
      algorithms; unlike computational approaches, they explore not only the
      conformational space but also the space of possible search strategies. The
      integration of human visual problem-solving and strategy development capabilities
      with traditional computational algorithms through interactive multiplayer games
      is a powerful new approach to solving computationally-limited scientific
      problems.

PMID- 20686578
TI  - Vectorial structure of an apertured Gaussian beam in the far field: an accurate
      method.
AB  - Based on the angular spectrum representation and the method of stationary phase,
      an analytical vectorial structure of an apertured Gaussian beam in the far field
      has been derived without any approximation that is concise and convenient to
      calculate. The analytical expressions of the energy flux of the transverse
      electric (TE) term, the transverse magnetic (TM) term, and the apertured Gaussian
      beam are also presented in the far field. The energy flux distributions of the TE
      term, the TM term, and the apertured Gaussian beam are numerically demonstrated
      in the far-field plane. The influences of the linearly polarized angle, the f
      parameter, and the truncation parameter on the energy flux distributions in the
      far field of the TE term, the TM term, and the apertured Gaussian beam are
      discussed in detail.

PMID- 20686575
TI  - Epigenetic silencing of engineered L1 retrotransposition events in human
      embryonic carcinoma cells.
AB  - Long interspersed element-1 (LINE-1 or L1) retrotransposition continues to affect
      human genome evolution. L1s can retrotranspose in the germline, during early
      development and in select somatic cells; however, the host response to L1
      retrotransposition remains largely unexplored. Here we show that reporter genes
      introduced into the genome of various human embryonic carcinoma-derived cell
      lines (ECs) by L1 retrotransposition are rapidly and efficiently silenced either
      during or immediately after their integration. Treating ECs with histone
      deacetylase inhibitors rapidly reverses this silencing, and chromatin
      immunoprecipitation experiments revealed that reactivation of the reporter gene
      was correlated with changes in chromatin status at the L1 integration site. Under
      our assay conditions, rapid silencing was also observed when reporter genes were
      delivered into ECs by mouse L1s and a zebrafish LINE-2 element, but not when
      similar reporter genes were delivered into ECs by Moloney murine leukaemia virus
      or human immunodeficiency virus, suggesting that these integration events are
      silenced by distinct mechanisms. Finally, we demonstrate that subjecting ECs to
      culture conditions that promote differentiation attenuates the silencing of
      reporter genes delivered by L1 retrotransposition, but that differentiation, in
      itself, is not sufficient to reactivate previously silenced reporter genes. Thus,
      our data indicate that ECs differ from many differentiated cells in their ability
      to silence reporter genes delivered by L1 retrotransposition.

PMID- 20686579
TI  - Geodesic distance on non-singular coherency matrix space in polarization optics.
AB  - We define a geodesic distance associated with the polarization space of non
      singular coherency matrices. Its introduction on HPD(2) (the manifold of
      Hermitian positive definite matrices of dimension 2) can be directly related to
      the Jones calculus. The expression of distance and related notion of mean value
      in this particular metric space are also presented. We investigate the properties
      of this geodesic distance and the classical Euclidean one and their
      appropriateness for interpixel comparisons in a context of imaging polarimetry.
      Finally, results are presented for a geodesic version of the classical K-means
      clustering algorithm with simulated data and real data. The results demonstrate
      the advantages of the geodesic approach.

PMID- 20686576
TI  - Branched tricarboxylic acid metabolism in Plasmodium falciparum.
AB  - A central hub of carbon metabolism is the tricarboxylic acid cycle, which serves
      to connect the processes of glycolysis, gluconeogenesis, respiration, amino acid
      synthesis and other biosynthetic pathways. The protozoan intracellular malaria
      parasites (Plasmodium spp.), however, have long been suspected of possessing a
      significantly streamlined carbon metabolic network in which tricarboxylic acid
      metabolism plays a minor role. Blood-stage Plasmodium parasites rely almost
      entirely on glucose fermentation for energy and consume minimal amounts of
      oxygen, yet the parasite genome encodes all of the enzymes necessary for a
      complete tricarboxylic acid cycle. Here, by tracing (13)C-labelled compounds
      using mass spectrometry we show that tricarboxylic acid metabolism in the human
      malaria parasite Plasmodium falciparum is largely disconnected from glycolysis
      and is organized along a fundamentally different architecture from the canonical
      textbook pathway. We find that this pathway is not cyclic, but rather is a
      branched structure in which the major carbon sources are the amino acids
      glutamate and glutamine. As a consequence of this branched architecture, several
      reactions must run in the reverse of the standard direction, thereby generating
      two-carbon units in the form of acetyl-coenzyme A. We further show that glutamine
      derived acetyl-coenzyme A is used for histone acetylation, whereas glucose
      derived acetyl-coenzyme A is used to acetylate amino sugars. Thus, the parasite
      has evolved two independent production mechanisms for acetyl-coenzyme A with
      different biological functions. These results significantly clarify our
      understanding of the Plasmodium metabolic network and highlight the ability of
      altered variants of central carbon metabolism to arise in response to unique
      environments.

PMID- 20686580
TI  - Coherence and visibility for vectorial light.
AB  - Two-path interference of transversal vectorial waves is embedded within a larger
      scheme: this is four-path interference between four scalar waves. This comprises
      previous approaches to coherence between vectorial waves and restores the
      equivalence between correlation-based coherence and visibility.

PMID- 20686581
TI  - Lateral superresolution using a posteriori phase shift estimation for a moving
      object: experimental results.
AB  - Structured illumination imaging uses multiple images of an object having
      different phase shifts in the sinusoidally patterned illumination to obtain
      lateral superresolution in stationary specimens in microscopy. In our recent work
      we have discussed a method to estimate these phase shifts a posteriori, allowing
      us to apply this technique to non-stationary objects such as in vivo tissue. Here
      we show experimental verification of our earlier simulations for phase shift
      estimation a posteriori. We estimated phase shifts in fluorescence microscopy
      images for an object having unknown, random translational motion and used them to
      obtain an artifact-free reconstruction having the expected superresolution.

PMID- 20686582
TI  - Optical properties of a nanomatch-like plasmonic structure.
AB  - The optical properties of a match-like plasmonic nanostructure are numerically
      investigated using full-wave finite-difference time-domain analysis in
      conjunction with dispersive material models. This work is mainly motivated by the
      developed technique enabling reproducible fabrication of nanomatch structures as
      well as the growing applications that utilize the localized field enhancement in
      plasmonic nanostructures. Our research revealed that due to the pronounced field
      enhancement and larger resonance tunabilities, some nanomatch topologies show
      potentials for various applications in the field of, e.g., sensing as well as a
      novel scheme for highly reproducible tips in scanning near field optical
      microscopy, among others. Despite the additional degrees of freedom that are
      offered by the composite nature of the proposed nanomatch topology, the paper
      also reflects on a fundamental complication intrinsic to the material interfaces
      especially in the nanoscale: stoichiometric mixing. We conclude that the
      specificity in material modeling will become a significant issue in future
      research on functionalized composite nanostructures.

PMID- 20686583
TI  - Analytic-domain lens design with proximate ray tracing.
AB  - We have developed an alternative approach to optical design which operates in the
      analytical domain so that an optical designer works directly with rays as
      analytical functions of system parameters rather than as discretely sampled
      polylines. This is made possible by a generalization of the proximate ray tracing
      technique which obtains the analytical dependence of the rays at the image
      surface (and ray path lengths at the exit pupil) on each system parameter. The
      resulting method provides an alternative direction from which to approach system
      optimization and supplies information which is not typically available to the
      system designer. In addition, we have further expanded the procedure to allow
      asymmetric systems and arbitrary order of approximation, and have illustrated the
      performance of the method through three lens design examples.

PMID- 20686584
TI  - Automated method for optimization of electric field distributions and optical
      parameters in thin-film polarizers.
AB  - An efficient method based on the modified needle optimization technique is
      proposed to design high-power laser thin-film polarizers. In order to minimize
      the influence of the standing-wave electric field on the laser-induced damage
      threshold of the polarizers, a crucial optimization parameter, the maximum
      electric field intensity in the high-refractive-index layers, is included in the
      proposed merit function. The electric field distribution and optical performance
      obtained by the proposed method are studied. Improved electric field and
      identical optical characteristics are observed in comparison with those of the
      designs obtained by optimizing the traditional merit function without a standing
      wave electric field term and by the analytical synthesis method.

PMID- 20686585
TI  - Speckle reduction mechanism in laser rear projection displays using a small
      moving diffuser.
AB  - Recently, a practical method of speckle reduction in laser rear projection
      displays that uses an optical system with a small moving diffuser has attracted
      much attention. In this paper, a model of the speckle generation and reduction
      mechanism in the system is presented. We investigated the speckle, focusing on
      the physical aspects of its generation, rather than treating it statistically. We
      found that the granularity of the speckle patterns generated by the small
      diffuser corresponded to the size of the coherent regions on the projection
      screen. This determined the efficiency of the speckle reduction when the small
      diffuser was rotated.

PMID- 20686586
TI  - Centroid displacement statistics of the eye aberration.
AB  - We discuss a method for the study of the spatial statistics of the ocular
      aberrations, based on the direct use of the Hartmann-Shack centroid
      displacements, avoiding the wavefront reconstruction step. Centroid diagrams are
      introduced as a helpful aid to visualize basic properties of the aberration
      datasets, and slope-related second-order statistical functions are applied to
      check the compatibility between the experimental data and different models for
      the aberration statistics. Preliminary results suggest that no single power-law
      spectrum (e.g., Kolmogorov's) is able to represent the whole range of spatial
      statistics of individual eye fluctuations and that more elaborated models,
      including at least the contribution of a relevant defocus fluctuation term, are
      required. This centroid-based approach allows for an easier intercomparison of
      results between laboratories and avoids the bias and information loss associated
      with the estimation of a reduced number of Zernike coefficients from a much wider
      slope data set.

PMID- 20686587
TI  - Bessel beam transformation by anisotropic crystals.
AB  - Transformation of Bessel beams by biaxial and uniaxial crystals is investigated
      experimentally and theoretically. Experimental observations show beam symmetry
      changing and formation of complex intensity patterns, depending on the
      orientation of the crystal. These patterns can appear as a regular system of peak
      intensities. Results of numerical calculations support the experimental findings.

PMID- 20686588
TI  - Annular beam scintillations in strong turbulence.
AB  - A scintillation index formulation for annular beams in strong turbulence is
      developed that is also valid in moderate and weak turbulence. In our derivation,
      a modified Rytov solution is employed to obtain the small-scale and large-scale
      scintillation indices of annular beams by utilizing the amplitude spatial
      filtering of the atmospheric spectrum. Our solution yields only the on-axis
      scintillation index for the annular beam and correctly reduces to the existing
      strong turbulence results for the Gaussian beam--thus plane and spherical wave
      scintillation indices--and also correctly yields the existing weak turbulence
      annular beam scintillations. Compared to collimated Gaussian beam, plane, and
      spherical wave scintillations, collimated annular beams seem to be advantageous
      in the weak regime but lose this advantage in strongly turbulent atmosphere. It
      is observed that the contribution of annular beam scintillations comes mainly
      from the small-scale effects. At a fixed primary beam size, the scintillations of
      thinner collimated annular beams compared to thicker collimated annular beams are
      smaller in moderate turbulence but larger in strong turbulence; however, thinner
      annular beams of finite focal length have a smaller scintillation index than the
      thicker annular beams in strong turbulence. Decrease in the focal length
      decreases the annular beam scintillations in strong turbulence. Examining
      constant area annular beams, smaller primary sized annular structures have larger
      scintillations in moderate but smaller scintillations in strong turbulence.

PMID- 20686589
TI  - Tilted Gaussian beam propagation in inhomogeneous media.
AB  - The present work is concerned with applying a ray-centered non-orthogonal
      coordinate system which is a priori matched to linearly-phased localized aperture
      field distributions. The resulting beam-waveobjects serve as the building blocks
      for beam-type spectral expansions of aperture fields in 2D inhomogeneous media
      that are characterized by a generic wave-velocity profile. By applying a rigorous
      paraxial-asymptotic analysis, a novel parabolic wave equation is obtained and
      termed "Non-orthogonal domain parabolic equation"--NoDope. Tilted Gaussian beams,
      which are exact solutions to this equation, match Gaussian aperture distributions
      over a plane that is tilted with respect to the beam-axes initial directions. A
      numerical example, which demonstrates the enhanced accuracy of the tilted
      Gaussian beams over the conventional ones, is presented as well.

PMID- 20686590
TI  - Multifractal zone plates.
AB  - We present multifractal zone plates (MFZPs) as what is to our knowledge a new
      family of diffractive lenses whose structure is based on the combination of
      fractal zone plates (FZPs) of different orders. The typical result is a composite
      of two FZPs with the central one having a first-order focal length f surrounded
      by outer zones with a third-order focal length f. The focusing properties of
      different members of this family are examined and compared with conventional
      composite Fresnel zone plates. It is shown that MFZPs improve the axial
      resolution and also give better performance under polychromatic illumination.

PMID- 20686591
TI  - On the single point resolution of on-axis digital holography.
AB  - On-axis digital holography (DH) is becoming widely used for its time-resolved
      three-dimensional (3D) imaging capabilities. A 3D volume can be reconstructed
      from a single hologram. DH is applied as a metrological tool in experimental
      mechanics, biology, and fluid dynamics, and therefore the estimation and the
      improvement of the resolution are current challenges. However, the resolution
      depends on experimental parameters such as the recording distance, the sensor
      definition, the pixel size, and also on the location of the object in the field
      of view. This paper derives resolution bounds in DH by using estimation theory.
      The single point resolution expresses the standard deviations on the estimation
      of the spatial coordinates of a point source from its hologram. Cramer-Rao lower
      bounds give a lower limit for the resolution. The closed-form expressions of the
      Cramer-Rao lower bounds are obtained for a point source located on and out of the
      optical axis. The influences of the 3D location of the source, the numerical
      aperture, and the signal-to-noise ratio are studied.

PMID- 20686592
TI  - Imaging of vibrating objects using speckle subtraction.
AB  - A simple method for imaging vibrational motion is proposed. The process consists
      of capturing two speckled images of a region illuminated by coherent radiation.
      One of the images is captured before the onset of motion and the other during
      motion. If the mean speckle intensity is below the threshold for detection or
      above the saturation intensity of the detector, subtracting the two images
      produces a high contrast image of the moving region. A theory is shown to agree
      well with experimental data.

PMID- 20686593
TI  - Reflectance spectra recovery from tristimulus values by adaptive estimation with
      metameric shape correction.
AB  - In this work a local optimization-based method that is able to recover the
      reflectance spectra with the desired tristimulus values, choosing the metamer
      with the most similar shape to the reflectances available in the training set, is
      proposed. Four different datasets of reflectance spectra and three different
      error metrics have been used in this study. According to all the error metrics
      considered, the proposed algorithm was able to recover the spectral reflectances
      with a higher accuracy than all the state of the art methods considered.

PMID- 20686594
TI  - Three-dimensional dispersive metallic photonic crystals with a bandgap and a high
      cutoff frequency.
AB  - The goal of this work is to analyze three-dimensional dispersive metallic
      photonic crystals (PCs) and to find a structure that can provide a bandgap and a
      high cutoff frequency. The determination of the band structure of a PC with
      dispersive materials is an expensive nonlinear eigenvalue problem; in this work
      we propose a rational-polynomial method to convert such a nonlinear eigenvalue
      problem into a linear eigenvalue problem. The spectral element method is extended
      to rapidly calculate the band structure of three-dimensional PCs consisting of
      realistic dispersive materials modeled by Drude and Drude-Lorentz models.
      Exponential convergence is observed in the numerical experiments. Numerical
      results show that, at the low frequency limit, metallic materials are similar to
      a perfect electric conductor, where the simulation results tend to be the same as
      perfect electric conductor PCs. Band structures of the scaffold structure and
      semi-woodpile structure metallic PCs are investigated. It is found that band
      structures of semi-woodpile PCs have a very high cutoff frequency as well as a
      bandgap between the lowest two bands and the higher bands.

PMID- 20686595
TI  - Equivalence of linear canonical transform domains to fractional Fourier domains
      and the bicanonical width product: a generalization of the space-bandwidth
      product.
AB  - Linear canonical transforms (LCTs) form a three-parameter family of integral
      transforms with wide application in optics. We show that LCT domains correspond
      to scaled fractional Fourier domains and thus to scaled oblique axes in the space
      frequency plane. This allows LCT domains to be labeled and ordered by the
      corresponding fractional order parameter and provides insight into the evolution
      of light through an optical system modeled by LCTs. If a set of signals is highly
      confined to finite intervals in two arbitrary LCT domains, the space-frequency
      (phase space) support is a parallelogram. The number of degrees of freedom of
      this set of signals is given by the area of this parallelogram, which is equal to
      the bicanonical width product but usually smaller than the conventional space
      bandwidth product. The bicanonical width product, which is a generalization of
      the space-bandwidth product, can provide a tighter measure of the actual number
      of degrees of freedom, and allows us to represent and process signals with fewer
      samples.

PMID- 20686597
TI  - People efficiently explore the solution space of the computationally intractable
      traveling salesman problem to find near-optimal tours.
AB  - Humans need to solve computationally intractable problems such as visual search,
      categorization, and simultaneous learning and acting, yet an increasing body of
      evidence suggests that their solutions to instantiations of these problems are
      near optimal. Computational complexity advances an explanation to this apparent
      paradox: (1) only a small portion of instances of such problems are actually
      hard, and (2) successful heuristics exploit structural properties of the typical
      instance to selectively improve parts that are likely to be sub-optimal. We
      hypothesize that these two ideas largely account for the good performance of
      humans on computationally hard problems. We tested part of this hypothesis by
      studying the solutions of 28 participants to 28 instances of the Euclidean
      Traveling Salesman Problem (TSP). Participants were provided feedback on the cost
      of their solutions and were allowed unlimited solution attempts (trials). We
      found a significant improvement between the first and last trials and that
      solutions are significantly different from random tours that follow the convex
      hull and do not have self-crossings. More importantly, we found that participants
      modified their current better solutions in such a way that edges belonging to the
      optimal solution ("good" edges) were significantly more likely to stay than other
      edges ("bad" edges), a hallmark of structural exploitation. We found, however,
      that more trials harmed the participants' ability to tell good from bad edges,
      suggesting that after too many trials the participants "ran out of ideas." In
      sum, we provide the first demonstration of significant performance improvement on
      the TSP under repetition and feedback and evidence that human problem-solving may
      exploit the structure of hard problems paralleling behavior of state-of-the-art
      heuristics.

PMID- 20686596
TI  - Memory consolidation in the cerebellar cortex.
AB  - Several forms of learning, including classical conditioning of the eyeblink,
      depend upon the cerebellum. In examining mechanisms of eyeblink conditioning in
      rabbits, reversible inactivations of the control circuitry have begun to
      dissociate aspects of cerebellar cortical and nuclear function in memory
      consolidation. It was previously shown that post-training cerebellar cortical,
      but not nuclear, inactivations with the GABAA agonist muscimol prevented
      consolidation but these findings left open the question as to how final memory
      storage was partitioned across cortical and nuclear levels. Memory consolidation
      might be essentially cortical and directly disturbed by actions of the muscimol,
      or it might be nuclear, and sensitive to the raised excitability of the nuclear
      neurons following the loss of cortical inhibition. To resolve this question, we
      simultaneously inactivated cerebellar cortical lobule HVI and the anterior
      interpositus nucleus of rabbits during the post-training period, so protecting
      the nuclei from disinhibitory effects of cortical inactivation. Consolidation was
      impaired by these simultaneous inactivations. Because direct application of
      muscimol to the nuclei alone has no impact upon consolidation, we can conclude
      that post-training, consolidation processes and memory storage for eyeblink
      conditioning have critical cerebellar cortical components. The findings are
      consistent with a recent model that suggests the distribution of learning-related
      plasticity across cortical and nuclear levels is task-dependent. There can be
      transfer to nuclear or brainstem levels for control of high-frequency responses
      but learning with lower frequency response components, such as in eyeblink
      conditioning, remains mainly dependent upon cortical memory storage.

PMID- 20686598
TI  - Exploring the genetic basis of variation in gene predictions with a synthetic
      association study.
AB  - Identifying DNA polymorphisms that affect molecular processes like transcription,
      splicing, or translation typically requires genotyping and experimentally
      characterizing tissue from large numbers of individuals, which remains expensive
      and time consuming. Here we introduce an alternative strategy: a "synthetic
      association study" in which we computationally predict molecular phenotypes on
      artificial genomes containing randomly sampled combinations of polymorphic
      alleles, and perform a classical association study to identify genotypes
      underlying variation in these computationally predicted annotations. We applied
      this method to characterize the effects on gene structure of 32,792 single
      nucleotide polymorphisms between two strains of the antibiotic producing fungus
      Penicilium chrysogenum. Although these SNPs represent only 0.1 percent of the
      nucleotides in the genome, they collectively altered 1.8 percent of predicted
      gene models between these strains. To determine which SNPs or combinations of
      SNPs were responsible for this variation, we predicted protein-coding genes in
      500 intermediate genomes, each identical except for randomly chosen alleles at
      each SNP position. Of 30,468 gene models in the genome, 557 varied across these
      500 genomes. 226 of these polymorphic gene models (40%) were perfectly correlated
      with individual SNPs, all of which were within or immediately proximal to the
      affected gene. The genetic architectures of the other 321 were more complex, with
      several examples of SNP epistasis that would have been difficult to predict a
      priori. We expect that many of the SNPs that affect computational gene structure
      reflect a biologically unrealistic sensitivity of the gene prediction algorithm
      to sequence changes, and we propose that genome annotation algorithms could be
      improved by minimizing their sensitivity to natural polymorphisms. However, many
      of the SNPs we identified are likely to affect transcript structure in vivo, and
      the synthetic association study approach can be easily generalized to any
      computed genome annotation to uncover relationships between genotype and
      important molecular phenotypes.

PMID- 20686599
TI  - Occupancy modeling, maximum contig size probabilities and designing metagenomics
      experiments.
AB  - Mathematical aspects of coverage and gaps in genome assembly have received
      substantial attention by bioinformaticians. Typical problems under consideration
      suppose that reads can be experimentally obtained from a single genome and that
      the number of reads will be set to cover a large percentage of that genome at a
      desired depth. In metagenomics experiments genomes from multiple species are
      simultaneously analyzed and obtaining large numbers of reads per genome is
      unlikely. We propose the probability of obtaining at least one contig of a
      desired minimum size from each novel genome in the pool without restriction based
      on depth of coverage as a metric for metagenomic experimental design. We derive
      an approximation to the distribution of maximum contig size for single genome
      assemblies using relatively few reads. This approximation is verified in
      simulation studies and applied to a number of different metagenomic experimental
      design problems, ranging in difficulty from detecting a single novel genome in a
      pool of known species to detecting each of a random number of novel genomes
      collectively sized and with abundances corresponding to given distributions in a
      single pool.

PMID- 20686600
TI  - Mutations of Francisella novicida that alter the mechanism of its phagocytosis by
      murine macrophages.
AB  - Infection with the bacterial pathogen Francisella tularensis tularensis (F.
      tularensis) causes tularemia, a serious and debilitating disease. Francisella
      tularensis novicida strain U112 (abbreviated F. novicida), which is closely
      related to F. tularensis, is pathogenic for mice but not for man, making it an
      ideal model system for tularemia. Intracellular pathogens like Francisella
      inhibit the innate immune response, thereby avoiding immune recognition and death
      of the infected cell. Because activation of inflammatory pathways may lead to
      cell death, we reasoned that we could identify bacterial genes involved in
      inhibiting inflammation by isolating mutants that killed infected cells faster
      than the wild-type parent. We screened a comprehensive transposon library of F.
      novicida for mutant strains that increased the rate of cell death following
      infection in J774 macrophage-like cells, as compared to wild-type F. novicida.
      Mutations in 28 genes were identified as being hypercytotoxic to both J774 and
      primary macrophages of which 12 were less virulent in a mouse infection model.
      Surprisingly, we found that F. novicida with mutations in four genes (lpcC, manB,
      manC and kdtA) were taken up by and killed macrophages at a much higher rate than
      the parent strain, even upon treatment with cytochalasin D (cytD), a classic
      inhibitor of macrophage phagocytosis. At least 10-fold more mutant bacteria were
      internalized by macrophages as compared to the parent strain if the bacteria were
      first fixed with formaldehyde, suggesting a surface structure is required for the
      high phagocytosis rate. However, bacteria were required to be viable for
      macrophage toxicity. The four mutant strains do not make a complete LPS but
      instead have an exposed lipid A. Interestingly, other mutations that result in an
      exposed LPS core were not taken up at increased frequency nor did they kill host
      cells more than the parent. These results suggest an alternative, more efficient
      macrophage uptake mechanism for Francisella that requires exposure of a specific
      bacterial surface structure(s) but results in increased cell death following
      internalization of live bacteria.

PMID- 20686601
TI  - Methicillin resistance transfer from Staphylocccus epidermidis to methicillin
      susceptible Staphylococcus aureus in a patient during antibiotic therapy.
AB  - BACKGROUND: The mecA gene, encoding methicillin resistance in staphylococci, is
      located on a mobile genetic element called Staphylococcal Cassette Chromosome mec
      (SCCmec). Horizontal, interspecies transfer of this element could be an important
      factor in the dissemination of methicillin-resistant S. aureus (MRSA).
      Previously, we reported the isolation of a closely related methicillin
      susceptible Staphylococcus aureus (MSSA), MRSA and potential SCCmec donor
      Staphylococcus epidermidis isolate from the same patient. Based on fingerprint
      techniques we hypothesized that the S. epidermidis had transferred SCCmec to the
      MSSA to become MRSA. The aim of this study was to show that these isolates form
      an isogenic pair and that interspecies horizontal SCCmec transfer occurred.
      METHODOLOGY/RESULTS: Whole genome sequencing of both isolates was performed and
      for the MSSA gaps were closed by conventional sequencing. The SCCmec of the S.
      epidermidis was also sequenced by conventional methods. The results show no
      difference in nucleotide sequence between the two isolates except for the
      presence of SCCmec in the MRSA. The SCCmec of the S. epidermidis and the MRSA are
      identical except for a single nucleotide in the ccrB gene, which results in a
      valine to alanine substitution. The main difference with the closely related
      EMRSA-16 is the presence of SaPI2 encoding toxic shock syndrome toxin and
      exfoliative toxin A in the MSSA-MRSA pair. No transfer of SCCmec from the S.
      epidermidis to the MSSA could be demonstrated in vitro. CONCLUSION: The MSSA and
      MRSA form an isogenic pair except for SCCmec. This strongly supports our
      hypothesis that the MRSA was derived from the MSSA by interspecies horizontal
      transfer of SCCmec from S. epidermidis O7.1.

PMID- 20686602
TI  - Establishment of protein delivery systems targeting podocytes.
AB  - BACKGROUND: Podocytes are uniquely structured cells that are critical to the
      kidney filtration barrier. Their anatomic location on the outer side of the
      glomerular capillaries expose podocytes to large quantities of both plasma and
      urinary components and thus are reachable for drug delivery. Recent years have
      made clear that interference with podocyte-specific disease pathways can modulate
      glomerular function and influence severity and progression of glomerular disease.
      METHODOLOGY/PRINCIPAL FINDINGS: Here, we describe studies that show efficient
      transport of proteins into the mammalian cells mouse 3T3 fibroblasts and
      podocytes, utilizing an approach termed profection. We are using synthetic lipid
      structures that allow the safe packing of proteins or antibodies resulting in the
      subsequent delivery of protein into the cell. The uptake of lipid coated protein
      is facilitated by the intrinsic characteristic of cells such as podocytes to
      engulf particles that are physiologically retained in the extracellular matrix.
      Profection of the restriction enzyme MunI in 3T3 mouse fibroblasts caused an
      increase in DNA degradation. Moreover, purified proteins such as beta
      galactosidase and the large GTPase dynamin could be profected into podocytes
      using two different profection reagents with the success rate of 95-100%. The
      delivered beta-galactosidase enzyme was properly folded and able to cleave its
      substrate X-gal in podocytes. Diseased podocytes are also potential recipients of
      protein cargo as we also delivered fluorophore labeled IgG into puromycin treated
      podocytes. We are currently optimizing our protocol for in vivo profection.
      CONCLUSIONS: Protein transfer is developing as an exciting tool to study and
      target highly differentiated cells such as podocytes.

PMID- 20686603
TI  - The 4q12 amplicon in malignant peripheral nerve sheath tumors: consequences on
      gene expression and implications for sunitinib treatment.
AB  - BACKGROUND: Malignant peripheral nerve sheath tumors (MPNST) are highly
      aggressive tumors which originate from Schwann cells and develop in about 10% of
      neurofibromatosis type 1 (NF1) patients. The five year survival rate is poor and
      more effective therapies are needed. Sunitinib is a drug targeting receptor
      tyrosine kinases (RTK) like PDGFRalpha, c-Kit and VEGFR-2. These genes are
      structurally related and cluster on chromosomal segment 4q12.
      METHODOLOGY/PRINCIPAL FINDINGS: Here we characterize this region by multiplex
      ligation-dependent probe amplification (MLPA) in MPNST. Our probe set encompasses
      the 3 adjacent RTK genes (PDGFRA, KIT, KDR) and 6 flanking genes. We found
      amplification of several genes within this region in a subset of MPNST and MPNST
      cell lines. Transcript and protein expression of PDGFRA matched well with its
      increased copy number suggesting a central role of PDGFRA within the amplicon.
      Studying the effect of sunitinib on 5 MPNST cell lines revealed that cell line
      S462 harboring the 4q12 amplicon was extremely sensitive to the drug with an IC50
      below 1.0 microM. Moreover, sunitinib induced apoptosis and prevented PDGF-AA
      induced signaling via PDGFRalpha as determined by western blotting. Co-expression
      of VEGF and its receptor VEGFR-2 (KDR) was present in MPNST cell lines suggesting
      an autocrine loop. We show that VEGF triggered signal transduction via the MAPK
      pathway, which could be blocked by sunitinib. CONCLUSIONS/SIGNIFICANCE: Since
      multiple receptors targeted by sunitinib are expressed or over-expressed by MPNST
      cells sunitinib appears as an attractive drug for treatment of MPNST patients.
      Presence of the 4q12 amplicon and subsequent over-expression of PDGFRA might
      serve as predictive markers for efficacy of sunitinib.

PMID- 20686604
TI  - Common ADRB2 haplotypes derived from 26 polymorphic sites direct beta2-adrenergic
      receptor expression and regulation phenotypes.
AB  - BACKGROUND: The beta2-adrenergic receptor (beta2AR) is expressed on numerous cell
      types including airway smooth muscle cells and cardiomyocytes. Drugs (agonists or
      antagonists) acting at these receptors for treatment of asthma, chronic
      obstructive pulmonary disease, and heart failure show substantial interindividual
      variability in response. The ADRB2 gene is polymorphic in noncoding and coding
      regions, but virtually all ADRB2 association studies have utilized the two common
      nonsynonymous coding SNPs, often reaching discrepant conclusions.
      METHODOLOGY/PRINCIPAL FINDINGS: We constructed the 8 common ADRB2 haplotypes
      derived from 26 polymorphisms in the promoter, 5'UTR, coding, and 3'UTR of the
      intronless ADRB2 gene. These were cloned into an expression construct lacking a
      vector-based promoter, so that beta2AR expression was driven by its promoter, and
      steady state expression could be modified by polymorphisms throughout ADRB2
      within a haplotype. "Whole-gene" transfections were performed with COS-7 cells
      and revealed 4 haplotypes with increased cell surface beta2AR protein expression
      compared to the others. Agonist-promoted downregulation of beta2AR protein
      expression was also haplotype-dependent, and was found to be increased for 2
      haplotypes. A phylogenetic tree of the haplotypes was derived and annotated by
      cellular phenotypes, revealing a pattern potentially driven by expression.
      CONCLUSIONS/SIGNIFICANCE: Thus for obstructive lung disease, the initial
      bronchodilator response from intermittent administration of beta-agonist may be
      influenced by certain beta2AR haplotypes (expression phenotypes), while other
      haplotypes may influence tachyphylaxis during the response to chronic therapy
      (downregulation phenotypes). An ideal clinical outcome of high expression and
      less downregulation was found for two haplotypes. Haplotypes may also affect
      heart failure antagonist therapy, where beta2AR increase inotropy and are anti
      apoptotic. The haplotype-specific expression and regulation phenotypes found in
      this transfection-based system suggest that the density of genetic information in
      the form of these haplotypes, or haplotype-clusters with similar phenotypes can
      potentially provide greater discrimination of phenotype in human disease and
      pharmacogenomic association studies.

PMID- 20686605
TI  - Calycosin promotes angiogenesis involving estrogen receptor and mitogen-activated
      protein kinase (MAPK) signaling pathway in zebrafish and HUVEC.
AB  - BACKGROUND: Angiogenesis plays an important role in a wide range of physiological
      processes, and many diseases are associated with the dysregulation of
      angiogenesis. Radix Astragali is a Chinese medicinal herb commonly used for
      treating cardiovascular disorders and has been shown to possess angiogenic effect
      in previous studies but its active constituent and underlying mechanism remain
      unclear. The present study investigates the angiogenic effects of calycosin, a
      major isoflavonoid isolated from Radix Astragali, in vitro and in vivo.
      METHODOLOGY: Tg(fli1:EGFP) and Tg(fli1:nEGFP) transgenic zebrafish embryos were
      treated with different concentrations of calycosin (10, 30, 100 microM) from 72
      hpf to 96 hpf prior morphological observation and angiogenesis phenotypes
      assessment. Zebrafish embryos were exposed to calycosin (10, 100 microM) from 72
      hpf to 78 hpf before gene-expression analysis. The effects of VEGFR tyrosine
      kinase inhibitor on calycosin-induced angiogenesis were studied using 72 hpf
      Tg(fli1:EGFP) and Tg(fli1:nEGFP) zebrafish embryos. The pro-angiogenic effects of
      calycosin were compared with raloxifene and tamoxifen in 72 hpf Tg(fli1:EGFP)
      zebrafish embryos. The binding affinities of calycosin to estrogen receptors
      (ERs) were evaluated by cell-free and cell-based estrogen receptor binding
      assays. Human umbilical vein endothelial cell cultures (HUVEC) were pretreated
      with different concentrations of calycosin (3, 10, 30, 100 microM) for 48 h then
      tested for cell viability and tube formation. The role of MAPK signaling in
      calycosin-induced angiogenesis was evaluated using western blotting. CONCLUSION:
      Calycosin was shown to induce angiogenesis in human umbilical vein endothelial
      cell cultures (HUVEC) in vitro and zebrafish embryos in vivo via the up
      regulation of vascular endothelial growth factor (VEGF), VEGFR1 and VEGFR2 mRNA
      expression. It was demonstrated that calycosin acted similar to other selective
      estrogen receptor modulators (SERMs), such as raloxifene and tamoxifen, by
      displaying selective potency and affinity to estrogen receptors ERalpha and
      ERbeta. Our results further indicated that calycosin promotes angiogenesis via
      activation of MAPK with the involvement of ERK1/2 and ER. Together, this study
      revealed, for the first time, that calycosin acts as a selective estrogen
      receptor modulator (SERM) to promote angiogenesis, at least in part through VEGF
      VEGFR2 and MAPK signaling pathways.

PMID- 20686606
TI  - Stat3 activates the receptor tyrosine kinase like orphan receptor-1 gene in
      chronic lymphocytic leukemia cells.
AB  - BACKGROUND: The receptor tyrosine kinase like orphan receptor (ROR)-1 gene is
      overexpressed in chronic lymphocytic leukemia (CLL). Because Stat3 is
      constitutively activated in CLL and sequence analysis revealed that the ROR1
      promoter harbors gamma-interferon activation sequence-like elements typically
      activated by Stat3, we hypothesized that Stat3 activates ROR1.
      METHODOLOGY/PRINCIPAL FINDINGS: Because IL-6 induced Stat3 phosphorylation and
      upregulated Ror1 protein levels in MM1 cells, we used these cells as a model. We
      transfected MM1 cells with truncated ROR1 promoter luciferase reporter constructs
      and found that IL-6 induced luciferase activity of ROR1-195 and upstream
      constructs. Co-transfection with Stat3 siRNA reduced the IL-6-induced luciferase
      activity, suggesting that IL-6 induced luciferase activity by activating Stat3.
      EMSA and the ChIP assay confirmed that Stat3 binds ROR1, and EMSA studies
      identified two Stat3 binding sites. In CLL cells, EMSA and ChIP studies
      determined that phosphorylated Stat3 bound to the ROR1 promoter at those two ROR1
      promoter sites, and ChIP analysis showed that Stat3 co-immunoprecipitated DNA of
      STAT3, ROR1, and several Stat3-regulated genes. Finally, like STAT3-siRNA in MM1
      cells, STAT3-shRNA downregulated STAT3, ROR1, and STAT3-regulated genes and Stat3
      and Ror1 protein levels in CLL cells. CONCLUSION/SIGNIFICANCE: Our data suggest
      that constitutively activated Stat3 binds to the ROR1 promoter and activates ROR1
      in CLL cells.

PMID- 20686607
TI  - The identification of protein kinase C iota as a regulator of the Mammalian heat
      shock response using functional genomic screens.
AB  - BACKGROUND: The heat shock response is widely used as a surrogate of the general
      protein quality control system within the cell. This system plays a significant
      role in aging and many protein folding diseases as well as the responses to other
      physical and chemical stressors. METHODS/PRINCIPAL FINDINGS: In this study, a
      broad-based functional genomics approach was taken to identify potential
      regulators of the mammalian heat shock response. In the primary screen, a total
      of 13724 full-length genes in mammalian expression vectors were individually co
      transfected into human embryonic kidney cells together with a human HSP70B
      promoter driving firefly luciferase. A subset of the full-length genes that
      showed significant activation in the primary screen were then evaluated for their
      ability to hyper-activate the HSP70B under heat shock conditions. Based on the
      results from the secondary assay and gene expression microarray analyses, eight
      genes were chosen for validation using siRNA knockdown. Of the eight genes, only
      PRKCI showed a statistically significant reduction in the heat shock response in
      two independent siRNA duplexes compared to scrambled controls. Knockdown of the
      PRKCI mRNA was confirmed using quantitative RT-PCR. Additional studies did not
      show a direct physical interaction between PRKCI and HSF1.
      CONCLUSIONS/SIGNIFICANCE: The results suggest that PRKCI is an indirect co
      regulator of HSF1 activity and the heat shock response. Given the underlying role
      of HSF1 in many human diseases and the response to environmental stressors, PRKCI
      represents a potentially new candidate for gene-environment interactions and
      therapeutic intervention.

PMID- 20686608
TI  - Genome-wide association study of pancreatic cancer in Japanese population.
AB  - Pancreatic cancer shows very poor prognosis and is the fifth leading cause of
      cancer death in Japan. Previous studies indicated some genetic factors
      contributing to the development and progression of pancreatic cancer; however,
      there are limited reports for common genetic variants to be associated with this
      disease, especially in the Asian population. We have conducted a genome-wide
      association study (GWAS) using 991 invasive pancreatic ductal adenocarcinoma
      cases and 5,209 controls, and identified three loci showing significant
      association (P-value<5x10(-7)) with susceptibility to pancreatic cancer. The SNPs
      that showed significant association carried estimated odds ratios of 1.29, 1.32,
      and 3.73 with 95% confidence intervals of 1.17-1.43, 1.19-1.47, and 2.24-6.21; P
      value of 3.30x10(-7), 3.30x10(-7), and 4.41x10(-7); located on chromosomes
      6p25.3, 12p11.21 and 7q36.2, respectively. These associated SNPs are located
      within linkage disequilibrium blocks containing genes that have been implicated
      some roles in the oncogenesis of pancreatic cancer.

PMID- 20686609
TI  - Comparative functional genomics analysis of NNK tobacco-carcinogen induced lung
      adenocarcinoma development in Gprc5a-knockout mice.
AB  - BACKGROUND: Improved understanding of lung cancer development and progression,
      including insights from studies of animal models, are needed to combat this fatal
      disease. Previously, we found that mice with a knockout (KO) of G-protein coupled
      receptor 5A (Gprc5a) develop lung tumors after a long latent period (12 to 24
      months). METHODOLOGY/PRINCIPAL FINDINGS: To determine whether a tobacco
      carcinogen will enhance tumorigenesis in this model, we administered 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) i.p. to 2-months old Gprc5a-KO
      mice and sacrificed groups (n=5) of mice at 6, 9, 12, and 18 months later.
      Compared to control Gprc5a-KO mice, NNK-treated mice developed lung tumors at
      least 6 months earlier, exhibited 2- to 4-fold increased tumor incidence and
      multiplicity, and showed a dramatic increase in lesion size. A gene expression
      signature, NNK-ADC, of differentially expressed genes derived by transcriptome
      analysis of epithelial cell lines from normal lungs of Gprc5a-KO mice and from
      NNK-induced adenocarcinoma was highly similar to differential expression patterns
      observed between normal and tumorigenic human lung cells. The NNK-ADC expression
      signature also separated both mouse and human adenocarcinomas from adjacent
      normal lung tissues based on publicly available microarray datasets. A key
      feature of the signature, up-regulation of Ube2c, Mcm2, and Fen1, was validated
      in mouse normal lung and adenocarcinoma tissues and cells by immunohistochemistry
      and western blotting, respectively. CONCLUSIONS/SIGNIFICANCE: Our findings
      demonstrate that lung tumorigenesis in the Gprc5a-KO mouse model is augmented by
      NNK and that gene expression changes induced by tobacco carcinogen(s) may be
      conserved between mouse and human lung epithelial cells. Further experimentation
      to prove the reliability of the Gprc5a knockout mouse model for the study of
      tobacco-induced lung carcinogenesis is warranted.

PMID- 20686610
TI  - Dendritic cells transduced to express interleukin 4 reduce diabetes onset in both
      normoglycemic and prediabetic nonobese diabetic mice.
AB  - BACKGROUND: We and others have previously demonstrated that treatment with bone
      marrow derived DC genetically modified to express IL-4 reduce disease pathology
      in mouse models of collagen-induced arthritis and delayed-type hypersensitivity.
      Moreover, treatment of normoglycemic NOD mice with bone marrow derived DC,
      genetically modified to express interleukin 4 (IL-4), reduces the onset of
      hyperglycemia in a significant number of animals. However, the mechanism(s)
      through which DC expressing IL-4 function to prevent autoimmune diabetes and
      whether this treatment can reverse disease in pre-diabetic NOD mice are unknown.
      METHODOLOGY/PRINCIPAL FINDINGS: DC were generated from the bone marrow of NOD
      mice and transduced with adenoviral vectors encoding soluble murine IL-4 (DC/sIL
      4), a membrane-bound IL-4 construct, or empty vector control. Female NOD mice
      were segregated into normoglycemic (<150 mg/dL) and prediabetic groups (between
      150 and 250 mg/dL) on the basis of blood glucose measurements, and randomized for
      adoptive transfer of 10(6) DC via a single i.v. injection. A single injection of
      DC/sIL-4, when administered to normoglycemic 12-week old NOD mice, significantly
      reduced the number of mice that developed diabetes. Furthermore, DC/sIL-4, but
      not control DC, decreased the number of mice progressing to diabetes when given
      to prediabetic NOD mice 12-16 weeks of age. DC/sIL-4 treatment also significantly
      reduced islet mononuclear infiltration and increased the expression of FoxP3 in
      the pancreatic lymph nodes of a subset of treated animals. Furthermore, DC/sIL-4
      treatment altered the antigen-specific Th2:Th1 cytokine profiles as determined by
      ELISPOT of splenocytes in treated animals. CONCLUSIONS: Adoptive transfer of DC
      transduced to express IL-4 into both normoglycemic and prediabetic NOD mice is an
      effective treatment for T1D.

PMID- 20686611
TI  - Alpha5beta1 integrin-fibronectin interactions specify liquid to solid phase
      transition of 3D cellular aggregates.
AB  - BACKGROUND: Tissue organization during embryonic development and wound healing
      depends on the ability of cells on the one hand to exchange adhesive bonds during
      active rearrangement and on the other to become fixed in place as tissue
      homeostasis is reached. Cells achieve these contradictory tasks by regulating
      either cell-cell adhesive bonds, mediated by cadherins, or cell-extracellular
      matrix (ECM) connections, regulated by integrins. Integrin alpha5beta1 and
      soluble fibronectin (sFN) are key players in cell-ECM force generation and in ECM
      polymerization. Here, we explore the interplay between integrin alpha5beta1 and
      sFN and its influence on tissue mechanical properties and cell sorting behavior.
      METHODOLOGY/PRINCIPAL FINDINGS: We generated a series of cell lines varying in
      alpha5beta1 receptor density. We then systematically explored the effects of
      different sFN concentrations on aggregate biomechanical properties using tissue
      surface tensiometry. We found previously unreported complex behaviors including
      the observation that interactions between fibronectin and integrin alpha5beta1
      generates biphasic tissue cohesion profiles. Specifically, we show that at
      constant sFn concentration, aggregate cohesion increases linearly as alpha5beta1
      receptor density is increased from low to moderate levels, producing a transition
      from viscoelastic-liquid to pseudo viscoelastic-solid behavior. However, further
      increase in receptor density causes an abrupt drop in tissue cohesion and a
      transition back to viscoelastic-liquid properties. We propose that this may be
      due to depletion of sFn below a critical value in the aggregate microenvironment
      at high alpha5beta1 levels. We also show that differential expression of
      alpha5beta1 integrin can promote phase-separation between cells.
      CONCLUSIONS/SIGNIFICANCE: The interplay between alpha5-integrin and sFn
      contributes significantly to tissue cohesion and, depending on their level of
      expression, can mediate a shift from liquid to elastic behavior. This interplay
      represents a tunable level of control between integrins and the ECM that can
      influence tissue cohesion and other mechanical properties, which may translate to
      the specification of tissue structure and function. These studies provide
      insights into important biological processes such as embryonic development, wound
      healing, and for tissue engineering applications.

PMID- 20686612
TI  - Mapping proprioception across a 2D horizontal workspace.
AB  - Relatively few studies have been reported that document how proprioception varies
      across the workspace of the human arm. Here we examined proprioceptive function
      across a horizontal planar workspace, using a new method that avoids active
      movement and interactions with other sensory modalities. We systematically mapped
      both proprioceptive acuity (sensitivity to hand position change) and bias
      (perceived location of the hand), across a horizontal-plane 2D workspace.
      Proprioception of both the left and right arms was tested at nine workspace
      locations and in 2 orthogonal directions (left-right and forwards-backwards).
      Subjects made repeated judgments about the position of their hand with respect to
      a remembered proprioceptive reference position, while grasping the handle of a
      robotic linkage that passively moved their hand to each judgement location. To
      rule out the possibility that the memory component of the proprioceptive testing
      procedure may have influenced our results, we repeated the procedure in a second
      experiment using a persistent visual reference position. Both methods resulted in
      qualitatively similar findings. Proprioception is not uniform across the
      workspace. Acuity was greater for limb configurations in which the hand was
      closer to the body, and was greater in a forward-backward direction than in a
      left-right direction. A robust difference in proprioceptive bias was observed
      across both experiments. At all workspace locations, the left hand was perceived
      to be to the left of its actual position, and the right hand was perceived to be
      to the right of its actual position. Finally, bias was smaller for hand positions
      closer to the body. The results of this study provide a systematic map of
      proprioceptive acuity and bias across the workspace of the limb that may be used
      to augment computational models of sensory-motor control, and to inform clinical
      assessment of sensory function in patients with sensory-motor deficits.

PMID- 20686614
TI  - Ecological meltdown in the Firth of Clyde, Scotland: two centuries of change in a
      coastal marine ecosystem.
AB  - BACKGROUND: The Firth of Clyde is a large inlet of the sea that extends over 100
      km into Scotland's west coast. METHODS: We compiled detailed fisheries landings
      data for this area and combined them with historical accounts to build a picture
      of change due to fishing activity over the last 200 years. FINDINGS: In the early
      19th century, prior to the onset of industrial fishing, the Firth of Clyde
      supported diverse and productive fisheries for species such as herring (Clupea
      harengus, Clupeidae), cod (Gadus morhua, Gadidae), haddock (Melanogrammus
      aeglefinus, Gadidae), turbot (Psetta maxima, Scophthalmidae) and flounder
      (Platichthys flesus, Pleuronectidae). The 19th century saw increased demand for
      fish, which encouraged more indiscriminate methods of fishing such as bottom
      trawling. During the 1880s, fish landings began to decline, and upon the
      recommendation of local fishers and scientists, the Firth of Clyde was closed to
      large trawling vessels in 1889. This closure remained in place until 1962 when
      bottom trawling for Norway lobster (Nephrops norvegicus, Nephropidae) was
      approved in areas more than three nautical miles from the coast. During the 1960s
      and 1970s, landings of bottomfish increased as trawling intensified. The trawl
      closure within three nautical miles of the coast was repealed in 1984 under
      pressure from the industry. Thereafter, bottomfish landings went into terminal
      decline, with all species collapsing to zero or near zero landings by the early
      21st century. Herring fisheries collapsed in the 1970s as more efficient mid
      water trawls and fish finders were introduced, while a fishery for mid-water
      saithe (Pollachius virens, Gadidae) underwent a boom and bust shortly after
      discovery in the late 1960s. The only commercial fisheries that remain today are
      for Nephrops and scallops (Pecten maximus, Pectinidae). SIGNIFICANCE: The Firth
      of Clyde is a marine ecosystem nearing the endpoint of overfishing, a time when
      no species remain that are capable of sustaining commercial catches. The evidence
      suggests that trawl closures helped maintain productive fisheries through the mid
      20th century, and their reopening precipitated collapse of bottomfish stocks. We
      argue that continued intensive bottom trawling for Nephrops with fine mesh nets
      will prevent the recovery of other species. This once diverse and highly
      productive environment will only be restored if trawl closures or other protected
      areas are re-introduced. The Firth of Clyde represents at a small scale a process
      that is occurring ocean-wide today, and its experience serves as a warning to
      others.

PMID- 20686613
TI  - Histological and functional benefit following transplantation of motor neuron
      progenitors to the injured rat spinal cord.
AB  - BACKGROUND: Motor neuron loss is characteristic of cervical spinal cord injury
      (SCI) and contributes to functional deficit. METHODOLOGY/PRINCIPAL FINDINGS: In
      order to investigate the amenability of the injured adult spinal cord to motor
      neuron differentiation, we transplanted spinal cord injured animals with a high
      purity population of human motor neuron progenitors (hMNP) derived from human
      embryonic stem cells (hESCs). In vitro, hMNPs displayed characteristic motor
      neuron-specific markers, a typical electrophysiological profile, functionally
      innervated human or rodent muscle, and secreted physiologically active growth
      factors that caused neurite branching and neuronal survival. hMNP transplantation
      into cervical SCI sites in adult rats resulted in suppression of intracellular
      signaling pathways associated with SCI pathogenesis, which correlated with
      greater endogenous neuronal survival and neurite branching. These neurotrophic
      effects were accompanied by significantly enhanced performance on all parameters
      of the balance beam task, as compared to controls. Interestingly, hMNP
      transplantation resulted in survival, differentiation, and site-specific
      integration of hMNPs distal to the SCI site within ventral horns, but hMNPs near
      the SCI site reverted to a neuronal progenitor state, suggesting an environmental
      deficiency for neuronal maturation associated with SCI. CONCLUSIONS/SIGNIFICANCE:
      These findings underscore the barriers imposed on neuronal differentiation of
      transplanted cells by the gliogenic nature of the injured spinal cord, and the
      physiological relevance of transplant-derived neurotrophic support to functional
      recovery.

PMID- 20686615
TI  - Specification of region-specific neurons including forebrain glutamatergic
      neurons from human induced pluripotent stem cells.
AB  - BACKGROUND: Directed differentiation of human induced pluripotent stem cells
      (hiPSC) into functional, region-specific neural cells is a key step to realizing
      their therapeutic promise to treat various neural disorders, which awaits
      detailed elucidation. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed neural
      differentiation from various hiPSC lines generated by others and ourselves.
      Although heterogeneity in efficiency of neuroepithelial (NE) cell differentiation
      was observed among different hiPSC lines, the NE differentiation process
      resembles that from human embryonic stem cells (hESC) in morphology, timing,
      transcriptional profile, and requirement for FGF signaling. NE cells
      differentiated from hiPSC, like those from hESC, can also form rostral phenotypes
      by default, and form the midbrain or spinal progenitors upon caudalization by
      morphogens. The rostrocaudal neural progenitors can further mature to develop
      forebrain glutamatergic projection neurons, midbrain dopaminergic neurons, and
      spinal motor neurons, respectively. Typical ion channels and action potentials
      were recorded in the hiPSC-derived neurons. CONCLUSIONS/SIGNIFICANCE: Our results
      demonstrate that hiPSC, regardless of how they were derived, can differentiate
      into a spectrum of rostrocaudal neurons with functionality, which supports the
      considerable value of hiPSC for study and treatment of patient-specific neural
      disorders.

PMID- 20686616
TI  - Rapid assessment of avoidable blindness in the Occupied Palestinian Territories.
AB  - BACKGROUND: There are no recent data on the prevalence and causes of blindness in
      the Occupied Palestinian Territories. The aim of our study was to estimate the
      prevalence and causes of blindness and visual impairment in the population aged
      50 years and above in the Occupied Palestinian Territories using the Rapid
      Assessment of Avoidable Blindness (RAAB) survey method. METHODS AND FINDINGS:
      Clusters of 40 people who were 50 years and above were selected with probability
      proportionate to size using a multistage cluster random sampling method.
      Participants received a comprehensive ophthalmic examination in their homes,
      including visual acuity testing by one of three experienced ophthalmologists. The
      principal cause for visual loss was determined by an experienced ophthalmologist
      using portable diagnostic instruments. Information about previous cataract
      surgery, satisfaction with surgery and barriers to cataract surgery were
      collected. The prevalence of self-reported diabetes was also determined. The
      prevalence of bilateral blindness (VA<3/60 in the better eye with available
      correction) was 3.4% (95% CI: 2.7-4.0), 2.0% (95% CI: 1.4-2.5) for severe visual
      impairment (VA>or=3/60 and <6/60), and 7.4% (95% CI: 6.4-8.3) for visual
      impairment (VA>or=6/60 and <6/18). Avoidable causes (i.e. cataract, refractive
      error, aphakia, surgical complications, corneal scarring and phthysis) accounted
      for 80.0% of bilateral blindness, severe visual impairment (70.7%) and visual
      impairment (86.2%). Cataract was the main cause of blindness (55.0%). The
      prevalence of blindness was higher in Gaza (4.9%, 95% CI: 3.7-6.1%) than in the
      West Bank (2.5%, 95% CI: 1.9-3.1%) and among women (4.3%,95% CI: 3.3-5.2%)
      compared to men (2.2%,95%CI:1.5-2.9%). Among people who had undergone cataract
      surgery in the past, only 54.5% of eyes obtained a good outcome (VA>or=6/18),
      23.2% had a borderline outcome (VA<6/18 and >or=6/60) and 22.3% had a poor
      outcome (VA<6/60) with available correction. The prevalence of self-reported
      diabetes mellitus in >or=50 year age group was 26.4% (95% CI: 24.9-27.9).
      CONCLUSIONS: The prevalence of blindness suggests that significant numbers of
      people in the Occupied Palestinian Territories exist who do not access eye care -
      predominantly women and those residing in Gaza. Programmes need to focus on
      maximizing the use of current services by these excluded groups.

PMID- 20686617
TI  - Gene flow between the Korean peninsula and its neighboring countries.
AB  - SNP markers provide the primary data for population structure analysis. In this
      study, we employed whole-genome autosomal SNPs as a marker set (54,836 SNP
      markers) and tested their possible effects on genetic ancestry using 320 subjects
      covering 24 regional groups including Northern (=16) and Southern (=3) Asians,
      Amerindians (=1), and four HapMap populations (YRI, CEU, JPT, and CHB).
      Additionally, we evaluated the effectiveness and robustness of 50K autosomal SNPs
      with various clustering methods, along with their dependencies on recombination
      hotspots (RH), linkage disequilibrium (LD), missing calls and regional specific
      markers. The RH- and LD-free multi-dimensional scaling (MDS) method showed a
      broad picture of human migration from Africa to North-East Asia on our genome
      map, supporting results from previous haploid DNA studies. Of the Asian groups,
      the East Asian group showed greater differentiation than the Northern and
      Southern Asian groups with respect to Fst statistics. By extension, the analysis
      of monomorphic markers implied that nine out of ten historical regions in South
      Korea, and Tokyo in Japan, showed signs of genetic drift caused by the later
      settlement of East Asia (South Korea, Japan and China), while Gyeongju in South
      East Korea showed signs of the earliest settlement in East Asia. In the genome
      map, the gene flow to the Korean Peninsula from its neighboring countries
      indicated that some genetic signals from Northern populations such as the
      Siberians and Mongolians still remain in the South East and West regions, while
      few signals remain from the early Southern lineages.

PMID- 20686618
TI  - A simple and sensitive method for measuring tumor-specific T cell cytotoxicity.
AB  - A simple and sensitive method to quantitatively measure the cytolytic effect of
      tumor-specific T killer cells is highly desirable for basic and clinical studies.
      Chromium (51Cr) release assay has been the "gold standard" for quantifying
      cytolytic activities of cytotoxic T lymphocytes (CTLs) against target cells and
      this method is still being used in many laboratories. However, a major drawback
      of this method is the use of radioactive materials, which is inconvenient to
      handle because of environmental safety concerns and expensive due to the short
      half-life of the isotope. Consequently, several nonradioactive methods have been
      reported recently. Here we report a new method that we recently developed for
      quantifying antigen-specific cytolytic activity of CTLs. This method fully
      exploits the high sensitivity and the relative simplicity of luciferase
      quantitative assay. We initially expected the released luciferase in the
      supernatant to be the adequate source for monitoring cell death. However, to our
      total surprise, incubation of these killer T cells with the tumor cell targets
      did not result in significant release of luciferase in the culture medium.
      Instead, we found that the remaining luciferase inside the cells could accurately
      reflect the overall cell viability.

PMID- 20686619
TI  - Axons amplify somatic incomplete spikes into uniform amplitudes in mouse cortical
      pyramidal neurons.
AB  - BACKGROUND: Action potentials are the essential unit of neuronal encoding.
      Somatic sequential spikes in the central nervous system appear various in
      amplitudes. To be effective neuronal codes, these spikes should be propagated to
      axonal terminals where they activate the synapses and drive postsynaptic neurons.
      It remains unclear whether these effective neuronal codes are based on spike
      timing orders and/or amplitudes. METHODOLOGY/PRINCIPAL FINDINGS: We investigated
      this fundamental issue by simultaneously recording the axon versus soma of
      identical neurons and presynaptic vs. postsynaptic neurons in the cortical
      slices. The axons enable somatic spikes in low amplitude be enlarged, which
      activate synaptic transmission in consistent patterns. This facilitation in the
      propagation of sequential spikes through the axons is mechanistically founded by
      the short refractory periods, large currents and high opening probability of
      axonal voltage-gated sodium channels. CONCLUSION/SIGNIFICANCE: An amplification
      of somatic incomplete spikes into axonal complete ones makes sequential spikes to
      activate consistent synaptic transmission. Therefore, neuronal encoding is likely
      based on spike timing order, instead of graded analogues.

PMID- 20686620
TI  - HDL interfere with the binding of T cell microparticles to human monocytes to
      inhibit pro-inflammatory cytokine production.
AB  - BACKGROUND: Direct cellular contact with stimulated T cells is a potent mechanism
      that induces cytokine production in human monocytes in the absence of an
      infectious agent. This mechanism is likely to be relevant to T cell-mediated
      inflammatory diseases such as rheumatoid arthritis and multiple sclerosis.
      Microparticles (MP) generated by stimulated T cells (MPT) display similar
      monocyte activating ability to whole T cells, isolated T cell membranes, or
      solubilized T cell membranes. We previously demonstrated that high-density
      lipoproteins (HDL) inhibited T cell contact- and MPT-induced production of IL
      1beta but not of its natural inhibitor, the secreted form of IL-1 receptor
      antagonist (sIL-1Ra). METHODOLOGY/PRINCIPAL FINDINGS: Labeled MPT were used to
      assess their interaction with monocytes and T lymphocytes by flow cytometry.
      Similarly, interactions of labeled HDL with monocytes and MPT were assessed by
      flow cytometry. In parallel, the MPT-induction of IL-1beta and sIL-1Ra production
      in human monocytes and the effect of HDL were assessed in cell cultures. The
      results show that MPT, but not MP generated by activated endothelial cells, bond
      monocytes to trigger cytokine production. MPT did not bind T cells. The
      inhibition of IL-1beta production by HDL correlated with the inhibition of MPT
      binding to monocytes. HDL interacted with MPT rather than with monocytes
      suggesting that they bound the activating factor(s) of T cell surface.
      Furthermore, prototypical pro-inflammatory cytokines and chemokines such as TNF,
      IL-6, IL-8, CCL3 and CCL4 displayed a pattern of production induced by MPT and
      inhibition by HDL similar to IL-1beta, whereas the production of CCL2, like that
      of sIL-1Ra, was not inhibited by HDL. CONCLUSIONS/SIGNIFICANCE: HDL inhibit both
      MPT binding to monocytes and the MPT-induced production of some but not all
      cytokines, shedding new light on the mechanism by which HDL display their anti
      inflammatory functions.

PMID- 20686621
TI  - Quantifying the proteolytic release of extracellular matrix-sequestered VEGF with
      a computational model.
AB  - BACKGROUND: VEGF proteolysis by plasmin or matrix metalloproteinases (MMPs) is
      believed to play an important role in regulating vascular patterning in vivo by
      releasing VEGF from the extracellular matrix (ECM). However, a quantitative
      understanding of the kinetics of VEGF cleavage and the efficiency of cell
      mediated VEGF release is currently lacking. To address these uncertainties, we
      develop a molecular-detailed quantitative model of VEGF proteolysis, used here in
      the context of an endothelial sprout. METHODOLOGY AND FINDINGS: To study a cell's
      ability to cleave VEGF, the model captures MMP secretion, VEGF-ECM binding, VEGF
      proteolysis from VEGF165 to VEGF114 (the expected MMP cleavage product of
      VEGF165) and VEGF receptor-mediated recapture. Using experimental data, we
      estimated the effective bimolecular rate constant of VEGF165 cleavage by plasmin
      to be 328 M(-1) s(-1) at 25 degrees C, which is relatively slow compared to
      typical MMP-ECM proteolysis reactions. While previous studies have implicated
      cellular proteolysis in growth factor processing, we show that single cells do
      not individually have the capacity to cleave VEGF to any appreciable extent (less
      than 0.1% conversion). In addition, we find that a tip cell's receptor system
      will not efficiently recapture the cleaved VEGF due to an inability of cleaved
      VEGF to associate with Neuropilin-1. CONCLUSIONS: Overall, VEGF165 cleavage in
      vivo is likely to be mediated by the combined effect of numerous cells, instead
      of behaving in a single-cell-directed, autocrine manner. We show that heparan
      sulfate proteoglycans (HSPGs) potentiate VEGF cleavage by increasing the VEGF
      clearance time in tissues. In addition, we find that the VEGF-HSPG complex is
      more sensitive to proteases than is soluble VEGF, which may imply its potential
      relevance in receptor signaling. Finally, according to our calculations,
      experimentally measured soluble protease levels are approximately two orders of
      magnitude lower than that needed to reconcile levels of VEGF cleavage seen in
      pathological situations.

PMID- 20686622
TI  - Transcriptional profiles of leukocyte populations provide a tool for interpreting
      gene expression patterns associated with high fat diet in mice.
AB  - BACKGROUND: Microarray experiments in mice have shown that high fat diet can lead
      to elevated expression of genes that are disproportionately associated with
      immune functions. These effects of high fat (atherogenic) diet may be due to
      infiltration of tissues by leukocytes in coordination with inflammatory
      processes. METHODOLOGY/PRINCIPAL FINDINGS: The Novartis strain-diet-sex
      microarray database (GSE10493) was used to evaluate the hepatic effects of high
      fat diet (4 weeks) in 12 mouse strains and both genders. We develop and apply an
      algorithm that identifies "signature transcripts" for many different leukocyte
      populations (e.g., T cells, B cells, macrophages) and uses this information to
      derive an in silico "inflammation profile". Inflammation profiles highlighted
      monocytes, macrophages and dendritic cells as key drivers of gene expression
      patterns associated with high fat diet in liver. In some strains (e.g., NZB/BINJ,
      B6), we estimate that 50-60% of transcripts elevated by high fat diet might be
      due to hepatic infiltration by these cell types. Interestingly, DBA mice appeared
      to exhibit resistance to localized hepatic inflammation associated with
      atherogenic diet. A common characteristic of infiltrating cell populations was
      elevated expression of genes encoding components of the toll-like receptor
      signaling pathway (e.g., Irf5 and Myd88). CONCLUSIONS/SIGNIFICANCE: High fat diet
      promotes infiltration of hepatic tissue by leukocytes, leading to elevated
      expression of immune-associated transcripts. The intensity of this effect is
      genetically controlled and sensitive to both strain and gender. The algorithm
      developed in this paper provides a framework for computational analysis of tissue
      remodeling processes and can be usefully applied to any in vivo setting in which
      inflammatory processes play a prominent role.

PMID- 20686623
TI  - Comparative genomic analyses identify the Vibrio harveyi genome sequenced strains
      BAA-1116 and HY01 as Vibrio campbellii.
AB  - Three notable members of the Harveyi clade, Vibrio harveyi, Vibrio alginolyticus
      and Vibrio parahaemolyticus, are best known as marine pathogens of commercial and
      medical import. In spite of this fact, the discrimination of Harveyi clade
      members remains difficult due to genetic and phenotypic similarities, and this
      has led to misidentifications and inaccurate estimations of a species'
      involvement in certain environments. To begin to understand the underlying
      genetics that complicate species level discrimination, we compared the genomes of
      Harveyi clade members isolated from different environments (seawater, shrimp,
      corals, oysters, finfish, humans) using microarray-based comparative genomic
      hybridization (CGH) and multilocus sequence analyses (MLSA). Surprisingly, we
      found that the only two V. harveyi strains that have had their genomes sequenced
      (strains BAA-1116 and HY01) have themselves been misidentified. Instead of
      belonging to the species harveyi, they are actually members of the species
      campbellii. In total, 28% of the strains tested were found to be misidentified
      and 42% of these appear to comprise a novel species. Taken together, our findings
      correct a number of species misidentifications while validating the ability of
      both CGH and MLSA to distinguish closely related members of the Harveyi clade.

PMID- 20686624
TI  - Bioequivalence of the 4-mg Oral Granules and Chewable Tablet Formulations of
      Montelukast.
AB  - PURPOSE: The primary objective of the studies was to demonstrate bioequivalence
      between the oral granules formulation and chewable tablet of montelukast in the
      fasted state. Effect of food on the pharmacokinetics of the oral granules was
      also evaluated. METHODS: The Formulation Biocomparison Study (Study 1) and the
      Final Market Image Study (Study 2) each used an open-label, randomized, 3-period
      crossover design where healthy adult subjects (N = 24 and 30, respectively)
      received montelukast as a single 4-mg dose of the oral granules formulation and a
      4-mg chewable tablet fasted, and a single 4-mg dose of the oral granules
      formulation with food (on 2 teaspoons of applesauce [Study 1] or after
      consumption of a high-fat breakfast [Study 2]). The formulations were to be
      considered bioequivalent if the 90% confidence intervals (CIs) for geometric mean
      ratios (GMRs) (oral granules/chewable tablet) for the AUC(0-infinity) and C(max)
      of montelukast were within the prespecified comparability bounds of (0.80, 1.25).
      For the food-effect assessment in Study 1, comparability bounds were prespecified
      as (0.50, 2.00) only for the 90% CI of the GMR (oral granules fed/oral granules
      fasted) for the AUC(0-infinity) of montelukast; the 90% CI of the GMR for the
      C(max) of montelukast, however, also was computed. In Study 2, 90% CIs of the
      GMRs (oral granules fed/oral granules fasted) for the AUC(0-infinity) and C(max)
      of montelukast were computed; comparability bounds were not prespecified.
      RESULTS: Comparing the exposure of the formulations, the 90% CIs of the GMRs for
      AUC(0-infinity) and C(max) were within the prespecified bound of (0.80, 1.25).
      For AUC(0-infinity), the GMRs (90% CI) for Study 1 and Study 2 were 1.01 (0.92,
      1.11) and 0.95 (0.91, 0.99), respectively. For C(max), respective values were
      0.99 (0.86, 1.13) and 0.92 (0.84, 1.01). When the oral granules formulation was
      administered with food, 90% CIs of the GMRs for both AUC(0-infinity) and C(max)
      in both studies were contained within the interval of (0.50, 2.00). CONCLUSIONS:
      The 4-mg oral granules and 4-mg chewable tablet formulations of montelukast
      administered in the fasted state are bioequivalent. Single 4-mg doses of the oral
      granules formulation and the chewable tablet of montelukast are generally well
      tolerated.

PMID- 20686625
TI  - COMPARING THE EFFECTIVENESS OF TWO FORMS OF TIME-SPACE SAMPLING TO IDENTIFY CLUB
      DRUG-USING YOUNG ADULTS.
AB  - Time-space sampling has been used to generate representative samples of both hard
      to-reach and location-based populations. Because of its emphasis on multi-tiered
      randomization (i.e., time, space, and individual), some have questioned the
      feasibility of time-space sampling as a cost-effective strategy. In an effort to
      better understand issues related to drug use among club-going young adults (ages
      18 to 29) in the New York City nightlife scene, two variations of time-space
      sampling methods were utilized and compared (Version 1: randomized venue, day,
      and individuals within venues: Version 2: randomized venue and day). A list of
      nightlife venues were randomized and survey teams approached potential
      participants as they entered or exited venues to conduct brief anonymous surveys.
      Over the course of 24 months, 18,169 approaches were conducted and 10,678
      consented to complete the brief questionnaire (V1 response rate = 46.0%, V2
      response rate = 62.5%). Drug use was fairly common, with nearly two-thirds of the
      sample reporting having ever tried an illegal drug and more than half of drug
      users specifically tried either MDMA/ecstasy and/or cocaine. There were few
      differences between young adults surveyed during Version 1 and Version 2. Time
      space sampling is an effective strategy to quickly detect and screen club drug
      users. Although caution is urged, elimination of the third tier of randomization
      (i.e., individual level counting) from time-space sampling may significantly
      improve response rates while only minimally impacting sample characteristics.

PMID- 20686626
TI  - Thick Silicon Double-Sided Strip Detectors for Low-Energy Small-Animal SPECT.
AB  - This work presents characterization studies of thick silicon double-sided strip
      detectors for a high-resolution small-animal SPECT. The dimension of these
      detectors is 60.4 mm * 60.4 mm * 1 mm. There are 1024 strips on each side that
      give the coordinates of the photon interaction, with each strip processed by a
      separate ASIC channel. Our measurement shows that intrinsic spatial resolution
      equivalent to the 59 MUm strip pitch is attainable. Good trigger uniformity can
      be achieved by proper setting of a 4-bit DAC in each ASIC channel to remove
      trigger threshold variations. This is particularly important for triggering at
      low energies. The thick silicon DSSD (Double-sided strip detector) shows high
      potential for small-animal SPECT.

PMID- 20686627
TI  - Cognitive Predictors of Medical Decision-Making Capacity in Traumatic Brain
      Injury.
AB  - OBJECTIVE: To identify cognitive predictors of medical decision-making capacity
      (MDC) in participants with traumatic brain injury (TBI) at time of acute injury
      (baseline) and at six-month follow-up. PARTICIPANTS: At baseline, participants
      were 34 adults with moderate to severe TBI and 20 healthy adults. At six-month
      follow-up, participants were 24 adults with moderate to severe TBI and 20 normal
      adults. MAIN OUTCOME MEASURES: Participants were administered a consent capacity
      instrument (Capacity to Consent to Treatment Instrument: CCTI) and
      neuropsychological test measures. In the TBI group, univariate and multivariate
      cognitive predictor models were developed at baseline and six-month follow-up for
      clinically relevant CCTI consent abilities/standards (S) of understanding (S5);
      reasoning (S4); and appreciation (S3). RESULTS: At baseline, measures of short
      term verbal memory and semantic fluency predicted TBI group performance on
      understanding (S5); short-term verbal memory and attention predicted performance
      on reasoning (S4); and working memory predicted performance on appreciation (S3).
      Regarding six-month follow-up models, measures of basic executive function,
      verbal processing speed, and working memory predicted TBI performance on
      understanding (S5); working memory and short-term memory predicted reasoning
      (S4); and basic executive functioning predicted appreciation (S3). CONCLUSIONS:
      Multiple cognitive functions are associated with acute impairment and partial
      recovery of MDC in patients with moderate to severe TBI. Short-term verbal memory
      was strongly associated with impairments in consent capacity in TBI participants
      at the time of acute inpatient hospitalization. As patients experience cognitive
      and functional recovery post-hospitalization, executive functioning and working
      memory abilities were associated with improved capacity at six-month follow-up.
      The results offer insight into the relationship between different standards of
      competency and cognitive changes and recovery following acute TBI.

PMID- 20686628
TI  - The Impact of Late-Life Parental Death on Adult Sibling Relationships: Do
      Parents' Advance Directives Help or Hurt?
AB  - The authors examined whether the effect of parental death on adults siblings'
      relationship quality varies on the basis of the presence and perceived
      effectiveness of a deceased parent's formal preparations for end-of-life care.
      The authors used data from the Wisconsin Longitudinal Study and focused on the
      relationship quality of a bereaved adult child and his or her randomly selected
      sibling. Parental death was associated with a decrease in sibling closeness. The
      parent's use of advance directives (living will and durable power of attorney for
      health care) did not have uniformly positive effects on adult siblings'
      relationship quality. Sibling relationships suffered when the living will was
      believed to "cause problems," but relationships improved when the deceased parent
      named someone other than his or her spouse or a child as durable power of
      attorney for health care. The authors discuss the implications for developing
      effective end-of-life preparations that benefit both the decedent and surviving
      kin.

PMID- 20686629
TI  - Self-Compassion, Stress, and Coping.
AB  - People who are high in self-compassion treat themselves with kindness and concern
      when they experience negative events. The present article examines the construct
      of self-compassion from the standpoint of research on coping in an effort to
      understand the ways in which people who are high in self-compassion cope with
      stressful events. Self-compassionate people tend to rely heavily on positive
      cognitive restructuring but do not appear to differ from less self-compassionate
      people in the degree to which they cope through problem-solving and distraction.
      Existing evidence does not show clear differences in the degree to which people
      who are low vs. high in self-compassion seek support as a coping strategy, but
      more research is needed.

PMID- 20686630
TI  - Community Ecology and Capacity: Keys to Progressing the Environmental
      Communication of Wicked Problems.
AB  - Wicked problems are multifactorial in nature and possess no clear resolution due
      to numerous community stakeholder involvement. We demonstrate childhood lead
      poisoning as a wicked problem and illustrate how understanding a community's
      ecology can build community capacity to affect local environmental management by
      (1) forming an academic-community partnership and (2) developing a place-specific
      strategy grounded in the cultural-experiential model of risk. We propose that
      practitioners need to consider a community's ecology and social context of risk
      as it pertains to wicked problems. These factors will determine how a diverse
      community interprets and responds to environmental communication and capacity
      building efforts.

PMID- 20686631
TI  - Estimating Risk: Stereotype Amplification and the Perceived Risk of Criminal
      Victimization.
AB  - This paper considers the process by which individuals estimate the risk of
      adverse events, with particular attention to the social context in which risk
      estimates are formed. We compare subjective probability estimates of crime
      victimization to actual victimization experiences among respondents from the 1994
      to 2002 waves of the Survey of Economic Expectations (Dominitz and Manski 2002).
      Using zip code identifiers, we then match these survey data to local area
      characteristics from the census. The results show that: (1) the risk of criminal
      victimization is significantly overestimated relative to actual rates of
      victimization or other negative events; (2) neighborhood racial composition is
      strongly associated with perceived risk of victimization, whereas actual
      victimization risk is driven by nonracial neighborhood characteristics; and (3)
      white respondents appear more strongly affected by racial composition than
      nonwhites in forming their estimates of risk. We argue these results support a
      model of stereotype amplification in the formation of risk estimates.
      Implications for persistent racial inequality are considered.

PMID- 20686632
TI  - Fluorous Mixture Synthesis of Four Stereoisomers of the C21-C40 Fragment of
      Tetrafibricin.
AB  - Four stereoisomers of the C21-C40 fragment are synthesized in a single exercise
      with the aid of fluorous tagging to encode configurations at C37 and C33. After
      demixing and detagging, the isomers were found to have substantially identical
      (1)H NMR spectra. However, there were some small but reliable differences in
      their (13)C NMR spectra.

PMID- 20686633
TI  - Bayesian Bigot? Statistical Discrimination, Stereotypes, and Employer Decision
      Making.
AB  - Much of the debate over the underlying causes of discrimination centers on the
      rationality of employer decision making. Economic models of statistical
      discrimination emphasize the cognitive utility of group estimates as a means of
      dealing with the problems of uncertainty. Sociological and social-psychological
      models, by contrast, question the accuracy of group-level attributions. Although
      mean differences may exist between groups on productivity-related
      characteristics, these differences are often inflated in their application,
      leading to much larger differences in individual evaluations than would be
      warranted by actual group-level trait distributions. In this study, the authors
      examine the nature of employer attitudes about black and white workers and the
      extent to which these views are calibrated against their direct experiences with
      workers from each group. They use data from fifty-five in-depth interviews with
      hiring managers to explore employers' group-level attributions and their direct
      observations to develop a model of attitude formation and employer learning.

PMID- 20686634
TI  - Deep Rationality: The Evolutionary Economics of Decision Making.
AB  - What is a "rational" decision? Economists traditionally viewed rationality as
      maximizing expected satisfaction. This view has been useful in modeling basic
      microeconomic concepts, but falls short in accounting for many everyday human
      decisions. It leaves unanswered why some things reliably make people more
      satisfied than others, and why people frequently act to make others happy at a
      cost to themselves. Drawing on an evolutionary perspective, we propose that
      people make decisions according to a set of principles that may not appear to
      make sense at the superficial level, but that demonstrate rationality at a deeper
      evolutionary level. By this, we mean that people use adaptive domain-specific
      decision-rules that, on average, would have resulted in fitness benefits. Using
      this framework, we re-examine several economic principles. We suggest that
      traditional psychological functions governing risk aversion, discounting of
      future benefits, and budget allocations to multiple goods, for example, vary in
      predictable ways as a function of the underlying motive of the decision-maker and
      individual differences linked to evolved life-history strategies. A deep
      rationality framework not only helps explain why people make the decisions they
      do, but also inspires multiple directions for future research.

PMID- 20686635
TI  - Confirmatory Factor Analysis and Test-Retest Reliability of the Alcohol and Drug
      Confrontation Scale (ADCS).
AB  - The addiction field lacks an accepted definition and reliable measure of
      confrontation. The Alcohol and Drug Confrontation Scale (ADCS) defines
      confrontation as warnings about the potential consequences of substance use. To
      assess psychometric properties, 323 individual entering recovery houses in U.S.
      urban and suburban areas were interviewed between 2003 and 2005 (20% women, 68%
      white). Analyses included test-retest reliability, confirmatory factor analysis,
      and measures of internal consistency. Findings support the ADCS as a reliable way
      of assessing two factors: Internal Support and External intensity. Confrontation
      was experienced as supportive, accurate and helpful. Additional studies should
      assess confrontation in different contexts.

PMID- 20686636
TI  - Validation of quantitative magnetic resonance (QMR) for determination of body
      composition in rats.
AB  - OBJECTIVE: To validate the use of quantitative magnetic resonance (QMR) to
      measure fat and lean mass in conscious rats. METHODS: Fifty Osborne-Mendel rats
      (249-770 g) were scanned using the Echo Medical 2 MHz body composition analyzer.
      Each rat was scanned under six settings (three acquisition times, with and
      without determination of total water). Precision was determined by the calculated
      coefficient of variation (CV) of three consecutive scans. Accuracy was determined
      by comparing the first scan to chemical carcass analysis and analyzed by paired t
      tests and least-squares regression analyses. Twenty-five rats were used in the
      validation study, and 25 in the cross-validation study. RESULTS: The precision
      for fat, lean and water at all settings was <1%. QMR significantly overestimated
      fat (~5%; P<0.0001), and underestimated both lean (~12.5%; P<0.0001) and total
      water (~5.5%; P<0.0001). All QMR measures were significantly correlated with
      carcass measures (r(2)>0.99; P<0.0001). Using prediction equations from the
      validation study with the cross-validation rats, there were no significant
      differences between QMR fat and carcass fat at any setting (P>0.400). For four of
      the six QMR settings, there were no significant differences between QMR and
      carcass lean (P>0.05). For total water, all QMR settings were significantly
      different than carcass (P<0.05), but only by ~1%. CONCLUSIONS: QMR showed
      excellent precision for the determination of fat, lean and water. Despite
      overestimating fat and underestimating lean and water, all were highly related to
      carcass values. When tested in the cross-validation group, QMR fat could be
      accurately predicted at all settings; however, lean mass (two settings) and water
      were still slightly different (less than 1%).

PMID- 20686638
TI  - Short exposure to light treatment improves depression scores in patients with
      seasonal affective disorder: A brief report.
AB  - Light therapy is an effective treatment of seasonal affective disorder (SAD),
      when administered daily for at least several weeks. We have previously reported a
      small improvement in mood in SAD patients following exposure to the first hour of
      treatment. We now reevaluate retrospectively mood changes during shorter
      exposures comparing depression ratings at baseline, 20, 40, and 60 minutes of
      light. Participants were 15 depressed patients with SAD, untreated, who were
      tested during the winter season. The treatment consisted of 10,000 lux of white
      cool fluorescent light. Depression was measured using the 24-item NIMH scale (24
      NIMH). The data were analyzed using ANOVA on ranks and Wilcoxon signed rank
      tests. Light resulted in significant improvement in mood at every interval when
      compared with baseline (p< .001). The 40 minute exposure resulted in a greater
      improvement than the 20 minute exposure (p < .001) but was not different from the
      60 minute exposure (p < = .068). We conclude that immediate improvement in mood
      can be detected after the first session of light with exposures as short as 20
      minutes, and that 40 minutes of exposure is not less effective than 60 minutes.

PMID- 20686639
TI  - HER2 specific delivery of methotrexate by dendrimer conjugated anti-HER2 mAb.
AB  - Herceptin, a humanized monoclonal antibody that binds to human growth factor
      receptor-2 (HER2), was covalently attached to a fifth-generation (G5)
      polyamidoamine dendrimer containing the cytotoxic drug methotrexate. The specific
      binding and internalization of this conjugate labeled with FITC was clearly
      demonstrated in cell lines overexpressing HER2 by flow cytometry as well as
      confocal microscopic analysis. In addition, binding and uptake of antibody
      conjugated dendrimers was completely blocked by excess non-conjugated herceptin.
      The dendrimer conjugate was also shown to inhibit the dihydrofolate reductase
      with similar activity to methotrexate. Co-localization experiments with
      lysotracker red indicate that antibody conjugate, although internalized
      efficiently into cells, has an unusually long residence time in the lysosome.
      Somewhat lower cytotoxicity of the conjugate in comparison to free methotrexate
      was attributed to the slow release of methotrexate from the conjugate and its
      long retention in the lysosomal pocket.

PMID- 20686640
TI  - Dielectrically Addressable Microspheres Engineered Using Self-Assembled
      Monolayers.
AB  - We have used self-assembled monolayer techniques to produce a new class of
      microspheres with specifically engineered dielectric properties to enable their
      dielectrophoretic manipulation and identification in microsystems.
      Dielectrophoresis is an electrokinetic phenomenon that exploits frequency
      dependent polarizability differences between a particle and its suspending medium
      to drive the movement of the particle toward or away from the high-field regions
      of an inhomogeneous electric field. While dielectrophoretic methods have been
      used extensively for cell manipulation, separation, and identification, we wished
      to extend the applicability of dielectrophoresis to molecular analysis by
      developing a panel of dielectric microspheres or "handles". Dielectric shell
      theory was used to model the dielectrophoretic response for a biomimetic particle
      composed of a thin insulating shell over a conductive interior. We specifically
      sought to modulate the specific capacitance, and thereby the dielectric
      properties, of the particle by controlling the thickness of the insulating layer.
      Such a structure was fabricated by covering a gold-coated polystyrene core
      particle with self-assembled monolayers of alkanethiol and phospholipid. To test
      the prediction that the carbon chain length of these layers should dictate the
      dielectric properties of the particles, we constructed a panel of six microsphere
      types with shell compositions ranging from a C(9) alkanethiol monolayer to a
      C(32) hybrid bilayer membrane. These microsphere populations were distinguishable
      and manipulatable by dielectrophoresis in a characteristic, frequency-dependent
      manner as predicted by theory. Experimentally derived specific membrane
      capacitance values were inversely related to the insulating shell thickness and
      agreed with published capacitance values for planar layers of similar
      thicknesses. These proof of principle studies are the first to demonstrate that
      the dielectric properties of particles can be specifically engineered to allow
      their dielectrophoretic manipulation and are a first step toward the development
      of bead-based dielectrophoretic microsystems for multiplexed molecular separation
      and analysis.

PMID- 20686641
TI  - Counterion adsorption on flexible polyelectrolytes: comparison of theories.
AB  - Counterion adsorption on a flexible polyelectrolyte chain in a spherical cavity
      is considered by taking a "permuted" charge distribution on the chain so that the
      "adsorbed" counterions are allowed to move along the backbone. We compute the
      degree of ionization by using self-consistent field theory (SCFT) and compare
      with the previously developed variational theory. Analysis of various
      contributions to the free energy in both theories reveals that the equilibrium
      degree of ionization is attained mainly as an interplay of the adsorption energy
      of counterions on the backbone, the translational entropy of the small ions, and
      their correlated density fluctuations. Degree of ionization computed from SCFT is
      significantly lower than that from the variational formalism. The difference is
      entirely due to the density fluctuations of the small ions in the system, which
      are accounted for in the variational procedure. When these fluctuations are
      deliberately suppressed in the truncated variational procedure, there emerges a
      remarkable quantitative agreement in the various contributing factors to the
      equilibrium degree of ionization, in spite of the fundamental differences in the
      approximations and computational procedures used in these two schemes.
      Furthermore, it is found that the total free energies from the truncated
      variational procedure and the SCFT are in quantitative agreement at low monomer
      densities and differ from each other at higher monomer densities. The
      disagreement at higher monomer densities is due to the inability of the
      variational calculation to accurately compute the solvent entropy at higher
      concentrations. A comparison of electrostatic energies (which are relatively
      small) reveals that the Debye-Huckel estimate used in the variational theory is
      an overestimation of electrostatic energy as compared to the Poisson-Boltzmann
      estimate. Nevertheless, since the significant effects from density fluctuations
      of small ions are not captured by the SCFT, and due to the close agreement
      between SCFT and the other contributing factors in the more transparent
      variational procedure, the latter is a better computational tool for obtaining
      the degree of ionization.

PMID- 20686642
TI  - Toward the Design of MR Agents for Imaging beta-Cell Function.
AB  - The chemistry of Gd(3+)-based MRI agents has advanced considerably during the
      past decade toward agents with higher relaxivity and agents that respond to
      physiology and/or metabolism. This review describes various approaches that have
      been taken toward the development of responsive contrast agents and discusses the
      importance of fast water exchange for advancement of targeted Gd(3+)-based agents
      with higher sensitivity. The recent discovery of Eu(3+) complexes having
      extraordinarily slow water exchange has opened a new avenue in contrast agent
      design based upon the chemical exchange saturation transfer (CEST) mechanism.
      These new paramagnetic complexes called PARACEST agents offer new possibilities
      of imaging biological functions such as tissue pH and metabolite levels. The
      lower detection limits that may apply to each class of contrast agent (Gd(3+)
      based versus PARACEST) are discussed and the extent to which they may be applied
      to the imaging of beta-cells is considered.

PMID- 20686643
TI  - Seroprevalence and HIV-associated factors among adults with severe mental illness
      - a vulnerable population.
AB  - BACKGROUND: Adults with severe mental illness (SMI) display an increased
      prevalence of HIV compared with the general population. Recommendations for
      provider-initiated testing in South Africa lack robust evidence because the
      studies - mainly from low-prevalence regions - overestimate the risk of HIV among
      adults with SMI. OBJECTIVE: We aimed to assess whether the mentally ill are a
      vulnerable population in South Africa. METHODS: All new admissions to an acute
      psychiatric ward from July to December 2000 were tested for HIV anonymously and
      the results linked with socio-demographic and clinical data. We did a restricted
      analysis of black females from a population-based survey of black females with
      SMI. RESULTS: There were 216 admissions, of whom 206 were included in the
      analysis. The seroprevalence of HIV-1 was 29.1% (confidence interval 27.8 -
      32.4); seroprevalence of HIV among the women was 40%. The following predicted HIV
      positivity: female (odds ratio (OR) 3.5 (1.7 - 6.9)), infections of the chest or
      central nervous system (OR 3.2 (1.4 - 7.5)), age group 30 - 39 years (OR 2.3 (1.1
      - 4.8)) and aggression on admission. The age and sex ratios among the SMI group
      were similar to the general population. Adults with SMI have an almost three
      times greater prevalence of HIV than the general population, after controlling
      for age and gender. CONCLUSIONS: Adults with SMI are a vulnerable population;
      therefore, provider-initiated HIV testing and other prevention and treatment
      programmes must be tailored to their needs.

PMID- 20686644
TI  - Enhanced Fluorescence from Fluorophores on Fractal Silver Surfaces.
AB  - Recent reports have shown enhanced fluorescence for fluorophores in close
      proximity to chemically deposited silver islands or colloids. To expand the
      usefulness of metal-enhanced fluorescence we tested fractal silver structures
      formed on, or near, silver electrodes by passage of electric currents. The
      emission intensity of fluorescein-labeled human serum albumin (FITC-HSA) was
      enhanced over 100-fold when adsorbed to the fractal silver structures as compared
      to glass. The amplitude-weighted lifetime is dramatically reduced to near 3 ps.
      Enhanced fluorescence was shown to result in selective observation of FITC-HSA
      over a fluorophore not attached to the silver surface. And finally,
      photostability measurements indicate 160-fold more photons are detectable from
      FITC-HSA on the fractal silver surface. These results suggest the use of in situ
      generated silver structures for metal-enhanced fluorescence.

PMID- 20686645
TI  - An Overview of Suicide Research in China.
AB  - Chinese suicide research did not start until the end of 1970s, when China opened
      its door to the West through reforming its economy. Although limited Chinese
      suicide research conducted overseas is published and known to the West, studies
      conducted by Chinese researchers and published in Chinese language, which may be
      of more significance, are rarely known or cited in the West. Further, researchers
      in China with direct observation of the suicidal environment may understand the
      suicide differently than scholars overseas with second hand information, and
      therefore derive different explanations of Chinese suicide. This current study
      overviews suicide research conducted in China and published in Chinese during the
      past two decades and compares the findings with what has been reported in Western
      publications. Six research books and 429 journal articles are reviewed. As units
      of analyses, all journal articles are quantified with 151 variables analyzed.
      Results support findings of previous studies in terms of the suicide rates by
      gender, age, and rural/urban location. A unique phenomenon in Chinese suicide
      noticed in the study is that married Chinese are at higher risk of suicide than
      the non-married. Hypotheses for future research are suggested based on the
      articles reviewed.

PMID- 20686646
TI  - Expression of transcription factor zinc-binding protein-89 (ZBP-89) is inhibited
      by inflammatory cytokines.
AB  - Zinc-binding protein-89 (ZBP-89; ZNF148, BERF-1, BFCOL-1) is a zinc-finger
      transcription factor of the Kruppel family. It has been shown to regulate the
      expression of a number of genes, acting as either an activator or repressor of
      gene expression, depending on the context. It is over-expressed in several
      cancers, but has been shown to be involved in apoptosis and to have a negative
      influence on cell growth in part by interactions with p53. Previously, ZBP-89 was
      shown to activate transcription of the matrix metalloproteinase-3 (MMP-3) gene by
      binding to a polymorphic promoter element in competition with nuclear factor
      kappaB (NF-kappaB). NF-kappaB is known to be a key regulator of the inflammatory
      response, but relatively little is known about regulation of ZBP-89. In order to
      ascertain whether ZBP-89 is regulated during inflammation, we designed
      experiments to determine whether and to what extent ZBP-89 levels are affected by
      inflammatory cytokines. Here we show that ZBP-89 mRNA and protein expression are
      significantly inhibited in human fibroblasts by the inflammatory cytokine
      interleukin-1beta. Since any change in the levels of ZBP-89 would presumably
      impact the regulation of MMP-3 and other ZBP-89 target genes, these results
      provide important insight into mechanisms involved in fine-tuning the immune
      response.

PMID- 20686647
TI  - NMR and Raman spectroscopic characterization of single walled carbon nanotube
      composites of polybutadiene.
AB  - Significant shifts of the frequency of the Raman spectra of the tangential mode
      of single walled carbon nanotubes (SWNTs) and fluorinated tubes (FSWNTs) in
      composites of polybutadiene (PB) were observed relative to the pristine SWNTs
      indicative of the interaction between the polymer and the SWNTs. Proton NMR line
      width measurements demonstrate partial suppression of polymer segmental motion
      for both types of nanotube composites and spin-lattice relaxation results
      indicate that short time-scale localized motions are also affected by SWNT
      inclusion, more so for FSWNTs. Hardness measurements as a function of wt% SWNTs
      and FSWNTs in the polymer show larger enhancements of hardness in the composite
      with the fluorinated tubes.

PMID- 20686648
TI  - Motivators and Barriers to Participation of Ethnic Minority Families in a Family
      Based HIV Prevention Program.
AB  - Involving low-income, ethnic minority families in lengthy HIV prevention programs
      can be challenging. Understanding the motivators and barriers to involvement may
      help researchers and practitioners design programs that can be used by
      populations most at risk for HIV exposure. The present study discusses motivators
      and barriers to involvement in the Collaborative HIV Prevention and Adolescent
      Mental Health Project (CHAMP), using data from a sample of 118 families that
      participated at varying levels in the twelve sessions of the program. Most
      participants chose motivators that reflect their perceptions of individual and/or
      family needs ("CHAMP might help me, mine, and other families"), and of
      characteristics of the program, such as CHAMP staff were friendly, CHAMP was fun.
      Among barriers to involvement, respondents expressed concerns about
      confidentiality, and about being judged by program staff. Respondents also
      reported experiencing many stressful events in their families (e.g., death and
      violence in the family) that may have been barriers to their involvement. Knowing
      these motivators and barriers, researchers and practitioners can enhance
      involvement in HIV prevention programs.

PMID- 20686649
TI  - Phthalates Biomarker Identification and Exposure Estimates in a Population of
      Pregnant Women.
AB  - Phthalates are known reproductive and developmental toxicants in experimental
      animals. However, in humans, there are few data on the exposure of pregnant women
      that can be used to assess the potential developmental exposure experienced by
      the fetus. We measured several phthalate metabolites in maternal urine, maternal
      serum, and cord serum samples collected at the time of delivery from 150 pregnant
      women from central New Jersey. The urinary concentrations of most metabolites
      were comparable to or less than among the U.S. general population, except for
      mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate
      (MEHHP), and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), three metabolites of
      di(2-ethylhexyl) phthalate (DEHP). The median urinary concentrations of MEHHP
      (109 mug/l) and MEOHP (95.1 mug/l) were more than 5 times their population-based
      concentrations, whereas the median urinary concentration of MEHP was more than 20
      times higher. High concentration of MEHP may indicate a recent exposure to the
      parent chemical DEHP in the hospital shortly before the collection of the
      samples. Calculation of daily intakes using the urinary biomarker data reveals
      that none of the pregnant women tested had integrated exposures to DEHP greater
      than the Agency for Toxic Substances and Disease Registry's minimal risk levels
      (MRLs chronic 60, intermediate 100 mug/kg/day). No abnormal birth outcomes (e
      .g., birth weight, Apgar Score, and gestational age) were noted in those newborns
      whose mothers had relatively greater exposure to DEHP during the perinatal period
      than others in this study. Significantly greater concentrations and detection
      frequencies in maternal urine than in maternal serum and cord serum suggest that
      the urinary concentrations of the phthalate metabolites may be more reliable
      biomarkers of exposure than their concentrations in other biological specimens.

PMID- 20686650
TI  - Electrical properties with relaxation through human blood.
AB  - The present work aims to study the effects of the blood-microstructure on the
      electrical conduction from two different but correlated properties: Electrical
      and mechanical (viscosity), and to derive useful parameters for the evaluation of
      electrical conduction as a function of the blood viscosity. ac-conductivity and
      dielectric constant of normal and diabetic blood are measured in the frequency
      range 10 kHz-1 MHz at the room temperature. An empirical relation relating the
      resistivity and viscosity of the blood has been presented. The results show that
      a microfluidic device is a viable and simple solution for determination of
      electrical and rheological behaviors of blood samples.

PMID- 20686651
TI  - Association of variants at UMOD with chronic kidney disease and kidney stones
      role of age and comorbid diseases.
AB  - Chronic kidney disease (CKD) is a worldwide public health problem that is
      associated with substantial morbidity and mortality. To search for sequence
      variants that associate with CKD, we conducted a genome-wide association study
      (GWAS) that included a total of 3,203 Icelandic cases and 38,782 controls. We
      observed an association between CKD and a variant with 80% population frequency,
      rs4293393-T, positioned next to the UMOD gene (GeneID: 7369) on chromosome 16p12
      (OR = 1.25, P = 4.1x10(-10)). This gene encodes uromodulin (Tamm-Horsfall
      protein), the most abundant protein in mammalian urine. The variant also
      associates significantly with serum creatinine concentration (SCr) in Icelandic
      subjects (N = 24,635, P = 1.3 x 10(-23)) but not in a smaller set of healthy
      Dutch controls (N = 1,819, P = 0.39). Our findings validate the association
      between the UMOD variant and both CKD and SCr recently discovered in a large
      GWAS. In the Icelandic dataset, we demonstrate that the effect on SCr increases
      substantially with both age (P = 3.0 x 10(-17)) and number of comorbid diseases
      (P = 0.008). The association with CKD is also stronger in the older age groups.
      These results suggest that the UMOD variant may influence the adaptation of the
      kidney to age-related risk factors of kidney disease such as hypertension and
      diabetes. The variant also associates with serum urea (P = 1.0 x 10(-6)), uric
      acid (P = 0.0064), and suggestively with gout. In contrast to CKD, the UMOD
      variant confers protection against kidney stones when studied in 3,617 Icelandic
      and Dutch kidney stone cases and 43,201 controls (OR = 0.88, P = 5.7 x 10(-5)).

PMID- 20686652
TI  - Plasmodium falciparum adhesion on human brain microvascular endothelial cells
      involves transmigration-like cup formation and induces opening of intercellular
      junctions.
AB  - Cerebral malaria, a major cause of death during malaria infection, is
      characterised by the sequestration of infected red blood cells (IRBC) in brain
      microvessels. Most of the molecules implicated in the adhesion of IRBC on
      endothelial cells (EC) are already described; however, the structure of the
      IRBC/EC junction and the impact of this adhesion on the EC are poorly understood.
      We analysed this interaction using human brain microvascular EC monolayers co
      cultured with IRBC. Our study demonstrates the transfer of material from the IRBC
      to the brain EC plasma membrane in a trogocytosis-like process, followed by a TNF
      enhanced IRBC engulfing process. Upon IRBC/EC binding, parasite antigens are
      transferred to early endosomes in the EC, in a cytoskeleton-dependent process.
      This is associated with the opening of the intercellular junctions. The transfer
      of IRBC antigens can thus transform EC into a target for the immune response and
      contribute to the profound EC alterations, including peri-vascular oedema,
      associated with cerebral malaria.

PMID- 20686653
TI  - Requirement of male-specific dosage compensation in Drosophila females-
      implications of early X chromosome gene expression.
AB  - Dosage compensation equates between the sexes the gene dose of sex chromosomes
      that carry substantially different gene content. In Drosophila, the single male X
      chromosome is hypertranscribed by approximately two-fold to effect this
      correction. The key genes are male lethal and appear not to be required in
      females, or affect their viability. Here, we show these male lethals do in fact
      have a role in females, and they participate in the very process which will
      eventually shut down their function--female determination. We find the male
      dosage compensation complex is required for upregulating transcription of the sex
      determination master switch, Sex-lethal, an X-linked gene which is specifically
      activated in females in response to their two X chromosomes. The levels of some X
      linked genes are also affected, and some of these genes are used in the process
      of counting the number of X chromosomes early in development. Our data suggest
      that before the female state is set, the ground state is male and female X
      chromosome expression is elevated. Females thus utilize the male dosage
      compensation process to amplify the signal which determines their fate.

PMID- 20686654
TI  - Oseltamivir-resistant pandemic H1N1/2009 influenza virus possesses lower
      transmissibility and fitness in ferrets.
AB  - The neuraminidase (NA) inhibitor oseltamivir offers an important immediate option
      for the control of influenza, and its clinical use has increased substantially
      during the recent H1N1 pandemic. In view of the high prevalence of oseltamivir
      resistant seasonal H1N1 influenza viruses in 2007-2008, there is an urgent need
      to characterize the transmissibility and fitness of oseltamivir-resistant
      H1N1/2009 viruses, although resistant variants have been isolated at a low rate.
      Here we studied the transmissibility of a closely matched pair of pandemic
      H1N1/2009 clinical isolates, one oseltamivir-sensitive and one resistant, in the
      ferret model. The resistant H275Y mutant was derived from a patient on
      oseltamivir prophylaxis and was the first oseltamivir-resistant isolate of the
      pandemic virus. Full genome sequencing revealed that the pair of viruses differed
      only at NA amino acid position 275. We found that the oseltamivir-resistant
      H1N1/2009 virus was not transmitted efficiently in ferrets via respiratory
      droplets (0/2), while it retained efficient transmission via direct contact
      (2/2). The sensitive H1N1/2009 virus was efficiently transmitted via both routes
      (2/2 and 1/2, respectively). The wild-type H1N1/2009 and the resistant mutant
      appeared to cause a similar disease course in ferrets without apparent
      attenuation of clinical signs. We compared viral fitness within the host by co
      infecting a ferret with oseltamivir-sensitive and -resistant H1N1/2009 viruses
      and found that the resistant virus showed less growth capability (fitness). The
      NA of the resistant virus showed reduced substrate-binding affinity and catalytic
      activity in vitro and delayed initial growth in MDCK and MDCK-SIAT1 cells. These
      findings may in part explain its less efficient transmission. The fact that the
      oseltamivir-resistant H1N1/2009 virus retained efficient transmission through
      direct contact underlines the necessity of continuous monitoring of drug
      resistance and characterization of possible evolving viral proteins during the
      pandemic.

PMID- 20686655
TI  - The role of chemokines during viral infection of the CNS.

PMID- 20686656
TI  - Bottlenecks and the maintenance of minor genotypes during the life cycle of
      Trypanosoma brucei.
AB  - African trypanosomes are digenetic parasites that undergo part of their
      developmental cycle in mammals and part in tsetse flies. We established a novel
      technique to monitor the population dynamics of Trypanosoma brucei throughout its
      life cycle while minimising the confounding factors of strain differences or
      variation in fitness. Clones derived from a single trypanosome were tagged with
      short synthetic DNA sequences in a non-transcribed region of the genome.
      Infections were initiated with mixtures of tagged parasites and a combination of
      polymerase chain reaction and deep sequencing were used to monitor the
      composition of populations throughout the life cycle. This revealed that a
      minimum of several hundred parasites survived transmission from a tsetse fly to a
      mouse, or vice versa, and contributed to the infection in the new host. In
      contrast, the parasites experienced a pronounced bottleneck during
      differentiation and migration from the midgut to the salivary glands of tsetse.
      In two cases a single tag accounted for > or =99% of the population in the
      glands, although minor tags could be also detected. Minor tags were transmitted
      to mice together with the dominant tag(s), persisted during a chronic infection,
      and survived transmission to a new insect host. An important outcome of the
      bottleneck within the tsetse is that rare variants can be amplified in individual
      flies and disseminated by them. This is compatible with the epidemic population
      structure of T. brucei, in which clonal expansion of a few genotypes in a region
      occurs against a background of frequent recombination between strains.

PMID- 20686657
TI  - Murine gamma-herpesvirus 68 hijacks MAVS and IKKbeta to initiate lytic
      replication.
AB  - Upon viral infection, the mitochondrial antiviral signaling (MAVS)-IKKbeta
      pathway is activated to restrict viral replication. Manipulation of immune
      signaling events by pathogens has been an outstanding theme of host-pathogen
      interaction. Here we report that the loss of MAVS or IKKbeta impaired the lytic
      replication of gamma-herpesvirus 68 (gammaHV68), a model herpesvirus for human
      Kaposi's sarcoma-associated herpesvirus and Epstein-Barr virus. gammaHV68
      infection activated IKKbeta in a MAVS-dependent manner; however, IKKbeta
      phosphorylated and promoted the transcriptional activation of the gammaHV68
      replication and transcription activator (RTA). Mutational analyses identified
      IKKbeta phosphorylation sites, through which RTA-mediated transcription was
      increased by IKKbeta, within the transactivation domain of RTA. Moreover, the
      lytic replication of recombinant gammaHV68 carrying mutations within the IKKbeta
      phosphorylation sites was greatly impaired. These findings support the conclusion
      that gammaHV68 hijacks the antiviral MAVS-IKKbeta pathway to promote viral
      transcription and lytic infection, representing an example whereby viral
      replication is coupled to host immune activation.

PMID- 20686658
TI  - The fitness landscapes of cis-acting binding sites in different promoter and
      environmental contexts.
AB  - The biophysical nature of the interaction between a transcription factor and its
      target sequences in vitro is sufficiently well understood to allow for the
      effects of DNA sequence alterations on affinity to be predicted. But even in
      relatively simple in vivo systems, the complexities of promoter organization and
      activity have made it difficult to predict how altering specific interactions
      between a transcription factor and DNA will affect promoter output. To better
      understand this, we measured the relative fitness of nearly all Escherichia coli
      sigma(70) -35 binding sites in different promoter and environmental contexts by
      competing four randomized -35 promoter libraries controlling the expression of
      the tetracycline resistance gene (tet)against each other in increasing
      concentrations of drug. We sequenced populations after competition to determine
      the relative enrichment of each -35 sequence. We observed a consistent
      relationship between the frequency of recovery of each -35 binding site and its
      predicted affinity for sigma(70) that varied depending on the sequence context of
      the promoter and drug concentration. Overall the relative fitness of each
      promoter could be predicted by a simple thermodynamic model of transcriptional
      regulation, in which the rate of transcriptional initiation (and hence fitness)
      is dependent upon the overall stability of the initiation complex, which in turn
      is dependent upon the energetic contributions of all sites within the complex. As
      implied by this model, a decrease in the free energy of association at one site
      could be compensated for by an increase in the binding energy at another to
      produce a similar output. Furthermore, these data show that a large and
      continuous range of transcriptional outputs can be accessed by merely changing
      the -35, suggesting that evolved or engineered mutations at this site could allow
      for subtle and precise control over gene expression.

PMID- 20686659
TI  - Discovery of a new human polyomavirus associated with trichodysplasia spinulosa
      in an immunocompromized patient.
AB  - The Polyomaviridae constitute a family of small DNA viruses infecting a variety
      of hosts. In humans, polyomaviruses can cause infections of the central nervous
      system, urinary tract, skin, and possibly the respiratory tract. Here we report
      the identification of a new human polyomavirus in plucked facial spines of a
      heart transplant patient with trichodysplasia spinulosa, a rare skin disease
      exclusively seen in immunocompromized patients. The trichodysplasia spinulosa
      associated polyomavirus (TSV) genome was amplified through rolling-circle
      amplification and consists of a 5232-nucleotide circular DNA organized similarly
      to known polyomaviruses. Two putative "early" (small and large T antigen) and
      three putative "late" (VP1, VP2, VP3) genes were identified. The TSV large T
      antigen contains several domains (e.g. J-domain) and motifs (e.g. HPDKGG, pRb
      family-binding, zinc finger) described for other polyomaviruses and potentially
      involved in cellular transformation. Phylogenetic analysis revealed a close
      relationship of TSV with the Bornean orangutan polyomavirus and, more distantly,
      the Merkel cell polyomavirus that is found integrated in Merkel cell carcinomas
      of the skin. The presence of TSV in the affected patient's skin was confirmed by
      newly designed quantitative TSV-specific PCR, indicative of a viral load of 10(5)
      copies per cell. After topical cidofovir treatment, the lesions largely resolved
      coinciding with a reduction in TSV load. PCR screening demonstrated a 4%
      prevalence of TSV in an unrelated group of immunosuppressed transplant recipients
      without apparent disease. In conclusion, a new human polyomavirus was discovered
      and identified as the possible cause of trichodysplasia spinulosa in
      immunocompromized patients. The presence of TSV also in clinically unaffected
      individuals suggests frequent virus transmission causing subclinical, probably
      latent infections. Further studies have to reveal the impact of TSV infection in
      relation to other populations and diseases.

PMID- 20686660
TI  - Breast cancer DNA methylation profiles are associated with tumor size and alcohol
      and folate intake.
AB  - Although tumor size and lymph node involvement are the current cornerstones of
      breast cancer prognosis, they have not been extensively explored in relation to
      tumor methylation attributes in conjunction with other tumor and patient dietary
      and hormonal characteristics. Using primary breast tumors from 162 (AJCC stage I
      IV) women from the Kaiser Division of Research Pathways Study and the Illumina
      GoldenGate methylation bead-array platform, we measured 1,413 autosomal CpG loci
      associated with 773 cancer-related genes and validated select CpG loci with
      Sequenom EpiTYPER. Tumor grade, size, estrogen and progesterone receptor status,
      and triple negative status were significantly (Q-values <0.05) associated with
      altered methylation of 209, 74, 183, 69, and 130 loci, respectively. Unsupervised
      clustering, using a recursively partitioned mixture model (RPMM), of all
      autosomal CpG loci revealed eight distinct methylation classes. Methylation class
      membership was significantly associated with patient race (P<0.02) and tumor size
      (P<0.001) in univariate tests. Using multinomial logistic regression to adjust
      for potential confounders, patient age and tumor size, as well as known disease
      risk factors of alcohol intake and total dietary folate, were all significantly
      (P<0.0001) associated with methylation class membership. Breast cancer prognostic
      characteristics and risk-related exposures appear to be associated with gene
      specific tumor methylation, as well as overall methylation patterns.

PMID- 20686661
TI  - Genome-wide analysis reveals novel genes essential for heme homeostasis in
      Caenorhabditis elegans.
AB  - Heme is a cofactor in proteins that function in almost all sub-cellular
      compartments and in many diverse biological processes. Heme is produced by a
      conserved biosynthetic pathway that is highly regulated to prevent the
      accumulation of heme--a cytotoxic, hydrophobic tetrapyrrole. Caenorhabditis
      elegans and related parasitic nematodes do not synthesize heme, but instead
      require environmental heme to grow and develop. Heme homeostasis in these
      auxotrophs is, therefore, regulated in accordance with available dietary heme. We
      have capitalized on this auxotrophy in C. elegans to study gene expression
      changes associated with precisely controlled dietary heme concentrations. RNA was
      isolated from cultures containing 4, 20, or 500 microM heme; derived cDNA probes
      were hybridized to Affymetrix C. elegans expression arrays. We identified 288
      heme-responsive genes (hrgs) that were differentially expressed under these
      conditions. Of these genes, 42% had putative homologs in humans, while genomes of
      medically relevant heme auxotrophs revealed homologs for 12% in both Trypanosoma
      and Leishmania and 24% in parasitic nematodes. Depletion of each of the 288 hrgs
      by RNA-mediated interference (RNAi) in a transgenic heme-sensor worm strain
      identified six genes that regulated heme homeostasis. In addition, seven membrane
      spanning transporters involved in heme uptake were identified by RNAi knockdown
      studies using a toxic heme analog. Comparison of genes that were positive in both
      of the RNAi screens resulted in the identification of three genes in common that
      were vital for organismal heme homeostasis in C. elegans. Collectively, our
      results provide a catalog of genes that are essential for metazoan heme
      homeostasis and demonstrate the power of C. elegans as a genetic animal model to
      dissect the regulatory circuits which mediate heme trafficking in both vertebrate
      hosts and their parasites, which depend on environmental heme for survival.

PMID- 20686662
TI  - DNA damage triggers genetic exchange in Helicobacter pylori.
AB  - Many organisms respond to DNA damage by inducing expression of DNA repair genes.
      We find that the human stomach pathogen Helicobacter pylori instead induces
      transcription and translation of natural competence genes, thus increasing
      transformation frequency. Transcription of a lysozyme-like protein that promotes
      DNA donation from intact cells is also induced. Exogenous DNA modulates the DNA
      damage response, as both recA and the ability to take up DNA are required for
      full induction of the response. This feedback loop is active during stomach
      colonization, indicating a role in the pathogenesis of the bacterium. As patients
      can be infected with multiple genetically distinct clones of H. pylori, DNA
      damage induced genetic exchange may facilitate spread of antibiotic resistance
      and selection of fitter variants through re-assortment of preexisting alleles in
      this important human pathogen.

PMID- 20686663
TI  - The meningococcal vaccine candidate neisserial surface protein A (NspA) binds to
      factor H and enhances meningococcal resistance to complement.
AB  - Complement forms an important arm of innate immunity against invasive
      meningococcal infections. Binding of the alternative complement pathway inhibitor
      factor H (fH) to fH-binding protein (fHbp) is one mechanism meningococci employ
      to limit complement activation on the bacterial surface. fHbp is a leading
      vaccine candidate against group B Neisseria meningitidis. Novel mechanisms that
      meningococci employ to bind fH could undermine the efficacy of fHbp-based
      vaccines. We observed that fHbp deletion mutants of some meningococcal strains
      showed residual fH binding suggesting the presence of a second receptor for fH.
      Ligand overlay immunoblotting using membrane fractions from one such strain
      showed that fH bound to a approximately 17 kD protein, identified by MALDI-TOF
      analysis as Neisserial surface protein A (NspA), a meningococcal vaccine
      candidate whose function has not been defined. Deleting nspA, in the background
      of fHbp deletion mutants, abrogated fH binding and mAbs against NspA blocked fH
      binding, confirming NspA as a fH binding molecule on intact bacteria. NspA
      expression levels vary among strains and expression correlated with the level of
      fH binding; over-expressing NspA enhanced fH binding to bacteria. Progressive
      truncation of the heptose (Hep) I chain of lipooligosaccharide (LOS), or
      sialylation of lacto-N-neotetraose LOS both increased fH binding to NspA
      expressing meningococci, while expression of capsule reduced fH binding to the
      strains tested. Similar to fHbp, binding of NspA to fH was human-specific and
      occurred through fH domains 6-7. Consistent with its ability to bind fH, deleting
      NspA increased C3 deposition and resulted in increased complement-dependent
      killing. Collectively, these data identify a key complement evasion mechanism
      with important implications for ongoing efforts to develop meningococcal vaccines
      that employ fHbp as one of its components.

PMID- 20686664
TI  - Transduction of human T cells with a novel T-cell receptor confers anti-HCV
      reactivity.
AB  - Hepatitis C Virus (HCV) is a major public health concern, with no effective
      vaccines currently available and 3% of the world's population being infected.
      Despite the existence of both B- and T-cell immunity in HCV-infected patients,
      chronic viral infection and HCV-related malignancies progress. Here we report the
      identification of a novel HCV TCR from an HLA-A2-restricted, HCV NS3:1073-1081
      reactive CTL clone isolated from a patient with chronic HCV infection. We
      characterized this HCV TCR by expressing it in human T cells and analyzed the
      function of the resulting HCV TCR-transduced cells. Our results indicate that
      both the HCV TCR-transduced CD4(+) and CD8(+) T cells recognized the HCV NS3:1073
      1081 peptide-loaded targets and HCV(+) hepatocellular carcinoma cells (HCC) in a
      polyfunctional manner with cytokine (IFN-gamma, IL-2, and TNF-alpha) production
      as well as cytotoxicity. Tumor cell recognition by HCV TCR transduced CD8(-)
      Jurkat cells and CD4(+) PBL-derived T cells indicated this TCR was CD8
      independent, a property consistent with other high affinity TCRs. HCV TCR
      transduced T cells may be promising for the treatment of patients with chronic
      HCV infections.

PMID- 20686665
TI  - Unexpected inheritance: multiple integrations of ancient bornavirus and
      ebolavirus/marburgvirus sequences in vertebrate genomes.
AB  - Vertebrate genomes contain numerous copies of retroviral sequences, acquired over
      the course of evolution. Until recently they were thought to be the only type of
      RNA viruses to be so represented, because integration of a DNA copy of their
      genome is required for their replication. In this study, an extensive sequence
      comparison was conducted in which 5,666 viral genes from all known non-retroviral
      families with single-stranded RNA genomes were matched against the germline
      genomes of 48 vertebrate species, to determine if such viruses could also
      contribute to the vertebrate genetic heritage. In 19 of the tested vertebrate
      species, we discovered as many as 80 high-confidence examples of genomic DNA
      sequences that appear to be derived, as long ago as 40 million years, from
      ancestral members of 4 currently circulating virus families with single strand
      RNA genomes. Surprisingly, almost all of the sequences are related to only two
      families in the Order Mononegavirales: the Bornaviruses and the Filoviruses,
      which cause lethal neurological disease and hemorrhagic fevers, respectively.
      Based on signature landmarks some, and perhaps all, of the endogenous virus-like
      DNA sequences appear to be LINE element-facilitated integrations derived from
      viral mRNAs. The integrations represent genes that encode viral nucleocapsid, RNA
      dependent-RNA-polymerase, matrix and, possibly, glycoproteins. Integrations are
      generally limited to one or very few copies of a related viral gene per species,
      suggesting that once the initial germline integration was obtained (or selected),
      later integrations failed or provided little advantage to the host. The
      conservation of relatively long open reading frames for several of the endogenous
      sequences, the virus-like protein regions represented, and a potential
      correlation between their presence and a species' resistance to the diseases
      caused by these pathogens, are consistent with the notion that their products
      provide some important biological advantage to the species. In addition, the
      viruses could also benefit, as some resistant species (e.g. bats) may serve as
      natural reservoirs for their persistence and transmission. Given the stringent
      limitations imposed in this informatics search, the examples described here
      should be considered a low estimate of the number of such integration events that
      have persisted over evolutionary time scales. Clearly, the sources of genetic
      information in vertebrate genomes are much more diverse than previously
      suspected.

PMID- 20686666
TI  - Biogenesis of the inner membrane complex is dependent on vesicular transport by
      the alveolate specific GTPase Rab11B.
AB  - Apicomplexan parasites belong to a recently recognised group of protozoa referred
      to as Alveolata. These protists contain membranous sacs (alveoli) beneath the
      plasma membrane, termed the Inner Membrane Complex (IMC) in the case of
      Apicomplexa. During parasite replication the IMC is formed de novo within the
      mother cell in a process described as internal budding. We hypothesized that an
      alveolate specific factor is involved in the specific transport of vesicles from
      the Golgi to the IMC and identified the small GTPase Rab11B as an alveolate
      specific Rab-GTPase that localises to the growing end of the IMC during
      replication of Toxoplasma gondii. Conditional interference with Rab11B function
      leads to a profound defect in IMC biogenesis, indicating that Rab11B is required
      for the transport of Golgi derived vesicles to the nascent IMC of the daughter
      cell. Curiously, a block in IMC biogenesis did not affect formation of sub
      pellicular microtubules, indicating that IMC biogenesis and formation of sub
      pellicular microtubules is not mechanistically linked. We propose a model where
      Rab11B specifically transports vesicles derived from the Golgi to the immature
      IMC of the growing daughter parasites.

PMID- 20686667
TI  - The role of coupled positive feedback in the expression of the SPI1 type three
      secretion system in Salmonella.
AB  - Salmonella enterica serovar Typhimurium is a common food-borne pathogen that
      induces inflammatory diarrhea and invades intestinal epithelial cells using a
      type three secretion system (T3SS) encoded within Salmonella pathogenicity island
      1 (SPI1). The genes encoding the SPI1 T3SS are tightly regulated by a network of
      interacting transcriptional regulators involving three coupled positive feedback
      loops. While the core architecture of the SPI1 gene circuit has been determined,
      the relative roles of these interacting regulators and associated feedback loops
      are still unknown. To determine the function of this circuit, we measured gene
      expression dynamics at both population and single-cell resolution in a number of
      SPI1 regulatory mutants. Using these data, we constructed a mathematical model of
      the SPI1 gene circuit. Analysis of the model predicted that the circuit serves
      two functions. The first is to place a threshold on SPI1 activation, ensuring
      that the genes encoding the T3SS are expressed only in response to the
      appropriate combination of environmental and cellular cues. The second is to
      amplify SPI1 gene expression. To experimentally test these predictions, we
      rewired the SPI1 genetic circuit by changing its regulatory architecture. This
      enabled us to directly test our predictions regarding the function of the circuit
      by varying the strength and dynamics of the activating signal. Collectively, our
      experimental and computational results enable us to deconstruct this complex
      circuit and determine the role of its individual components in regulating SPI1
      gene expression dynamics.

PMID- 20686669
TI  - COMBINING DIFFERENT SUBSTANCES IN THE DANCE SCENE: ENHANCING PLEASURE, MANAGING
      RISK AND TIMING EFFECTS.

PMID- 20686668
TI  - Patterns of HIV-1 protein interaction identify perturbed host-cellular
      subsystems.
AB  - Human immunodeficiency virus type 1 (HIV-1) exploits a diverse array of host cell
      functions in order to replicate. This is mediated through a network of virus-host
      interactions. A variety of recent studies have catalogued this information. In
      particular the HIV-1, Human Protein Interaction Database (HHPID) has provided a
      unique depth of protein interaction detail. However, as a map of HIV-1 infection,
      the HHPID is problematic, as it contains curation error and redundancy; in
      addition, it is based on a heterogeneous set of experimental methods. Based on
      identifying shared patterns of HIV-host interaction, we have developed a novel
      methodology to delimit the core set of host-cellular functions and their
      associated perturbation from the HHPID. Initially, using biclustering, we
      identify 279 significant sets of host proteins that undergo the same types of
      interaction. The functional cohesiveness of these protein sets was validated
      using a human protein-protein interaction network, gene ontology annotation and
      sequence similarity. Next, using a distance measure, we group host protein sets
      and identify 37 distinct higher-level subsystems. We further demonstrate the
      biological significance of these subsystems by cross-referencing with global
      siRNA screens that have been used to detect host factors necessary for HIV-1
      replication, and investigate the seemingly small intersect between these data
      sets. Our results highlight significant host-cell subsystems that are perturbed
      during the course of HIV-1 infection. Moreover, we characterise the patterns of
      interaction that contribute to these perturbations. Thus, our work disentangles
      the complex set of HIV-1-host protein interactions in the HHPID, reconciles these
      with siRNA screens and provides an accessible and interpretable map of infection.

PMID- 20686670
TI  - The Effects of Storage Conditions on the Preservation of Enzymatic Activity in
      Bone.
AB  - Alkaline phosphatase and acid phosphatase are two major enzymatic measures of
      osteoblastic and osteoclastic activity, respectively. As a result, the
      preservation of the enzymes in bone specimens to near in vivo accuracy is
      essential. Despite standardization of the staining process, several factors
      related to the storage of blocks and slides before sectioning and staining impact
      the level of enzymes detected in the tissue. Block condition (intact, faced, or
      unstained) as well as environment (temperature and length of time in storage)
      affect alkaline phosphatase preservation while the acid phosphatase enzyme
      remains unaffected. We conclude that to optimally preserve alkaline phosphatase
      enzyme, methacrylate-embedded undecalcified murine bones should be stored as
      intact blocks. After sectioning, the faced blocks should be stored at 4 degrees C
      for optimal enzyme staining of future sections. Furthermore, it is best to stain
      sections immediately after sectioning.

PMID- 20686671
TI  - Active Segmentation.
AB  - The human visual system observes and understands a scene/image by making a series
      of fixations. Every fixation point lies inside a particular region of arbitrary
      shape and size in the scene which can either be an object or just a part of it.
      We define as a basic segmentation problem the task of segmenting that region
      containing the fixation point. Segmenting the region containing the fixation is
      equivalent to finding the enclosing contour- a connected set of boundary edge
      fragments in the edge map of the scene - around the fixation. This enclosing
      contour should be a depth boundary.We present here a novel algorithm that finds
      this bounding contour and achieves the segmentation of one object, given the
      fixation. The proposed segmentation framework combines monocular cues
      (color/intensity/texture) with stereo and/or motion, in a cue independent manner.
      The semantic robots of the immediate future will be able to use this algorithm to
      automatically find objects in any environment. The capability of automatically
      segmenting objects in their visual field can bring the visual processing to the
      next level. Our approach is different from current approaches. While existing
      work attempts to segment the whole scene at once into many areas, we segment only
      one image region, specifically the one containing the fixation point. Experiments
      with real imagery collected by our active robot and from the known databases 1
      demonstrate the promise of the approach.

PMID- 20686672
TI  - Mitochondrial and Plasma Membrane Citrate Transporters: Discovery of Selective
      Inhibitors and Application to Structure/Function Analysis.
AB  - Cytoplasmic citrate is the prime carbon source for fatty acid, triacylglycerol,
      and cholesterol biosyntheses, and also regulates glucose metabolism via its
      allosteric inhibition of phosphofructokinase. It originates either via the efflux
      of citrate from the mitochondrial matrix on the inner membrane citrate transport
      protein (CTP) or via the influx of extracellular citrate on the plasma membrane
      citrate transporter (PMCT). Despite their common substrate, the two transport
      proteins share little sequence similarity and they transport citrate via
      fundamentally different mechanisms. We tested the ability of a set of previously
      identified CTP inhibitors, to inhibit the PMCT. We found that of the top 10 CTP
      inhibitors only one substantially inhibited the PMCT. Conversely, we identified
      two other inhibitors that inhibited the PMCT but had little effect on the CTP.
      All three identified PMCT inhibitors displayed a noncompetitive mechanism.
      Furthermore, models to explain inhibitor interactions with the CTP are proposed.
      As part of the present studies a PMCT homology model has been developed based on
      the crystal structure of the leucine transporter, and a possible citrate binding
      site has been identified and its composition compared with the two known citrate
      binding sites present within the CTP. The ability to selectively inhibit the PMCT
      may prove key to the pharmacologic amelioration of metabolic disorders resulting
      from the synthesis of excess lipid, cholesterol, and glucose, including human
      obesity, hyperlipidemia, hyper-cholesterolemia, and Type 2 diabetes.

PMID- 20686673
TI  - The "Two faces" of Tumor Suppressor p53-revisited.
AB  - About 15 years ago, several groups including ours had used matched pairs of cell
      lines carrying wild type or mutant p53 genes to ascertain a role for p53 in cell
      survival. These were isogenic cell lines differing only by p53 status. The trend
      at that time was to support p53-mediated apoptosis. Accordingly, p53-wildtype
      cells were sensitive to DNA damage compared to p53-mutant cells which were
      thought to evade apoptosis. However, this finding was not universal. In
      particular, after UV-radiation, p53-mutant cells were more sensitive than their
      wild type p53 counterparts in several studies. The finding that p53 controlled a
      major DNA repair pathway, nucleotide excision repair (NER) which repairs UV
      damage, provided a mechanism for the observations. We coined the term "the two
      faces of tumor suppressor p53" to illustrate that p53 can on one hand induce
      apoptosis leading to cell sensitivity, but p53 can also enhance the rate of DNA
      repair thereby protecting cells from DNA damage. This concept has gained
      acceptance and has been expanded to other DNA-damaging agents. New insights into
      how p53 is "switched" from a protective function to an apoptotic function are
      reviewed.

PMID- 20686674
TI  - Antimalarial Preclinical Drug Development: A Single Oral Dose of A 5-Carbon
      linked Trioxane Dimer Plus Mefloquine Cures Malaria-Infected Mice.
AB  - Three new 5-carbon-linked trioxane dimer carboxylate esters have been prepared
      from the natural trioxane, artemisinin in only 3-steps and 40-50% overall yields.
      Each one of these new chemical entities is at least as efficacious as the
      clinically used trioxane antimalarial drug artemether when combined with
      mefloquine hydrochloride in a low single oral dose cure.

PMID- 20686676
TI  - Reply to letter to the editor: "MEASURES OF OBESITY AND CARDIOVASCULAR RISK AMONG
      MEN AND WOMEN"

PMID- 20686675
TI  - Promoting HIV Vaccine Research in African American Communities: Does the Theory
      of Reasoned Action Explain Potential Outcomes of Involvement?
AB  - The HIV/AIDS pandemic continues to challenge the African American community with
      disproportionate rates of infection, particularly among young women ages 25 to 34
      years. Development of a preventive HIV vaccine may bring a substantial turning
      point in this health crisis. Engagement of the African American community is
      necessary to improve awareness of the effort and favorably influence attitudes
      and referent norms. The Theory of Reasoned Action (TRA) may be a useful framework
      for exploration of community engagement outcomes including future attendance,
      community mobilization, and study participation. Within the context of HIV
      vaccine outreach, we conducted a cross-sectional survey in early 2007 with 175
      African-American adults (>/= 18 years). Confirmatory factor analysis and
      structural equation modeling were performed and the findings support the
      potential of the model in understanding behavioral intentions toward HIV vaccine
      research.

PMID- 20686677
TI  - A Closer Look at Men Who Sustain Intimate Terrorism by Women.
AB  - Over 30 years of research has established that both men and women are capable of
      sustaining intimate partner violence (IPV) by their opposite-sex partners, yet
      little research has examined men's experiences in such relationships. Some
      experts in the field have forwarded assumptions about men who sustain IPV-for
      example, that the abuse they experience is trivial or humorous and of no
      consequence and that, if their abuse was severe enough, they have the financial
      and psychological resources to easily leave the relationship-but these
      assumptions have little data to support them. The present study is an in-depth,
      descriptive examination of 302 men who sustained severe IPV from their women
      partners within the previous year and sought help. We present information on
      their demographics, overall mental health, and the types and frequency of various
      forms of physical and psychological IPV they sustained. We also provide both
      quantitative and qualitative information about their last physical argument and
      their reasons for staying in the relationship. It is concluded that, contrary to
      many assumptions about these men, the IPV they sustain is quite severe and both
      mentally and physically damaging; their most frequent response to their partner's
      IPV is to get away from her; and they are often blocked in their efforts to
      leave, sometimes physically, but more often because of strong psychological and
      emotional ties to their partners and especially their children. These results are
      discussed in terms of their implications for policy and practice.

PMID- 20686679
TI  - Multiresolution Multiscale Active Mask Segmentation of Fluorescence Microscope
      Images.
AB  - We propose an active mask segmentation framework that combines the advantages of
      statistical modeling, smoothing, speed and flexibility offered by the traditional
      methods of region-growing, multiscale, multiresolution and active contours
      respectively. At the crux of this framework is a paradigm shift from evolving
      contours in the continuous domain to evolving multiple masks in the discrete
      domain. Thus, the active mask framework is particularly suited to segment digital
      images. We demonstrate the use of the framework in practice through the
      segmentation of punctate patterns in fluorescence microscope images. Experiments
      reveal that statistical modeling helps the multiple masks converge from a random
      initial configuration to a meaningful one. This obviates the need for an involved
      initialization procedure germane to most of the traditional methods used to
      segment fluorescence microscope images. While we provide the mathematical details
      of the functions used to segment fluorescence microscope images, this is only an
      instantiation of the active mask framework. We suggest some other instantiations
      of the framework to segment different types of images.

PMID- 20686680
TI  - G Protein-Coupled Receptor 87: a Promising Opportunity for Cancer Drug Discovery.
AB  - G protein-coupled receptors (GPRs) constitute one of the largest families of
      membrane proteins encoded by the human genome. Upon binding to various ligands,
      these seven-transmembrane receptors play an essential role in many physiological
      processes, including neurotransmission, immunity, inflammation, regulation of
      mood and behavior. In view of their important functions, aberrant expression and
      activity of GPRs have been implicated in a wide spectrum of diseases, including
      tumorigenesis. GPR87, a cell surface GPR related to the LPA receptor family, is
      overexpressed in diverse carcinomas and plays an essential role in tumor cell
      survival. In our recent work, we uncovered that GPR87 expression is regulated by
      the tumor suppressor p53 and by DNA damage in a p53-dependent manner. Moreover,
      we found that a lack of GPR87 triggers an increase in p53, concomitant with a
      decrease in Akt, which results in the sensitization of tumor cells to DNA damage
      induced apoptosis and growth suppression. Altogether, we uncovered an essential
      function for GPR87 in p53-dependent cell survival in response to stress signals.
      Due to their unique structure, localization and ligand binding ability, GPRs have
      been extensively used for drug development and are the most common targets of
      commercial drugs. Although studies are required to determine GPR87 natural
      ligand(s) and signaling pathways, GPR87 is undoubtedly a very promising novel
      target for cancer prevention and treatment.

PMID- 20686681
TI  - The effect of surface nanometre-scale morphology on protein adsorption.
AB  - BACKGROUND: Protein adsorption is the first of a complex series of events that
      regulates many phenomena at the nano-bio interface, e.g. cell adhesion and
      differentiation, in vivo inflammatory responses and protein crystallization. A
      quantitative understanding of how nanoscale morphology influences protein
      adsorption is strategic for providing insight into all of these processes,
      however this understanding has been lacking until now. METHODOLOGY/PRINCIPAL
      FINDINGS: Here we introduce novel methods for quantitative high-throughput
      characterization of protein-surface interaction and we apply them in an
      integrated experimental strategy, to study the adsorption of a panel of proteins
      on nanostructured surfaces. We show that the increase of nanoscale roughness
      (from 15 nm to 30 nm) induces a decrease of protein binding affinity (<or=90%)
      and a relevant increase in adsorbed proteins (<or=500%) beyond the corresponding
      increase of specific area. We demonstrate that these effects are caused by
      protein nucleation on the surface, which is promoted by surface nanoscale pores.
      CONCLUSIONS/SIGNIFICANCE: These results show that the adsorption of proteins
      depends significantly on surface nanostructure and that the relevant
      morphological parameter regulating the protein adsorption process is the
      nanometric pore shape. These new findings improve our understanding of the role
      of nanostructures as a biomaterial design parameter and they have important
      implications for the general understanding of cell behavior on nanostructured
      surfaces.

PMID- 20686682
TI  - The roots of bioinformatics in protein evolution.

PMID- 20686683
TI  - Knotted vs. unknotted proteins: evidence of knot-promoting loops.
AB  - Knotted proteins, because of their ability to fold reversibly in the same
      topologically entangled conformation, are the object of an increasing number of
      experimental and theoretical studies. The aim of the present investigation is to
      assess, on the basis of presently available structural data, the extent to which
      knotted proteins are isolated instances in sequence or structure space, and to
      use comparative schemes to understand whether specific protein segments can be
      associated to the occurrence of a knot in the native state. A significant
      sequence homology is found among a sizeable group of knotted and unknotted
      proteins. In this family, knotted members occupy a primary sub-branch of the
      phylogenetic tree and differ from unknotted ones only by additional loop
      segments. These "knot-promoting" loops, whose virtual bridging eliminates the
      knot, are found in various types of knotted proteins. Valuable insight into how
      knots form, or are encoded, in proteins could be obtained by targeting these
      regions in future computational studies or excision experiments.

PMID- 20686684
TI  - Astrocyte-derived vascular endothelial growth factor stabilizes vessels in the
      developing retinal vasculature.
AB  - Vascular endothelial growth factor (VEGF) plays a critical role in normal
      development as well as retinal vasculature disease. During retinal
      vascularization, VEGF is most strongly expressed by not yet vascularized retinal
      astrocytes, but also by retinal astrocytes within the developing vascular plexus,
      suggesting a role for retinal astrocyte-derived VEGF in angiogenesis and vessel
      network maturation. To test the role of astrocyte-derived VEGF, we used Cre-lox
      technology in mice to delete VEGF in retinal astrocytes during development.
      Surprisingly, this only had a minor impact on retinal vasculature development,
      with only small decreases in plexus spreading, endothelial cell proliferation and
      survival observed. In contrast, astrocyte VEGF deletion had more pronounced
      effects on hyperoxia-induced vaso-obliteration and led to the regression of
      smooth muscle cell-coated radial arteries and veins, which are usually resistant
      to the vessel-collapsing effects of hyperoxia. These results suggest that VEGF
      production from retinal astrocytes is relatively dispensable during development,
      but performs vessel stabilizing functions in the retinal vasculature and might be
      relevant for retinopathy of prematurity in humans.

PMID- 20686685
TI  - A comprehensive, quantitative, and genome-wide model of translation.
AB  - Translation is still poorly characterised at the level of individual proteins and
      its role in regulation of gene expression has been constantly underestimated. To
      better understand the process of protein synthesis we developed a comprehensive
      and quantitative model of translation, characterising protein synthesis
      separately for individual genes. The main advantage of the model is that basing
      it on only a few datasets and general assumptions allows the calculation of many
      important translational parameters, which are extremely difficult to measure
      experimentally. In the model, each gene is attributed with a set of translational
      parameters, namely the absolute number of transcripts, ribosome density, mean
      codon translation time, total transcript translation time, total time required
      for translation initiation and elongation, translation initiation rate, mean mRNA
      lifetime, and absolute number of proteins produced by gene transcripts. Most
      parameters were calculated based on only one experimental dataset of genome-wide
      ribosome profiling. The model was implemented in Saccharomyces cerevisiae, and
      its results were compared with available data, yielding reasonably good
      correlations. The calculated coefficients were used to perform a global analysis
      of translation in yeast, revealing some interesting aspects of the process. We
      have shown that two commonly used measures of translation efficiency - ribosome
      density and number of protein molecules produced - are affected by two distinct
      factors. High values of both measures are caused, i.a., by very short times of
      translation initiation, however, the origins of initiation time reduction are
      completely different in both cases. The model is universal and can be applied to
      any organism, if the necessary input data are available. The model allows us to
      better integrate transcriptomic and proteomic data. A few other possibilities of
      the model utilisation are discussed concerning the example of the yeast system.

PMID- 20686686
TI  - Time spent for activation of non-profit studies in oncology in Italy.
AB  - AIM: The aim of this paper is to describe the time spent to activate oncological
      non-profit clinical trials promoted in Italy by the National Cancer Institute of
      Naples, following the implementation of recent European laws. METHODOLOGY: Data
      about the process of activation of 5 non-profit multicentre clinical trials were
      prospectively collected through a web-based system. The impact of European
      guidelines was assessed by comparing the efficiency of the process between
      applications started before and after the decree introducing in Italy the
      Clinical Trial Application form (MD-CTA). Outcomes of the descriptive analyses
      were the time to EC opinion, the time to administrative agreement signature after
      a positive EC opinion, and the cumulative percentage of submissions that came to
      closure (either positive or negative) within four subsequent time cohorts.
      PRINCIPAL FINDINGS: From March 2007 to October 2009, 202 applications were
      submitted to 107 centres. Forty-four (59%) applications of those submitted before
      were successful, compared to 71 (55%) of those submitted after MD-CTA. Most of
      the failures were due to missing EC response (27% and 22%) or administrative
      reasons (10% and 16%, before and after, respectively); very few (4% and 7%) were
      due to EC refusal. The impact of the MD-CTA on time to EC opinion looked positive
      (median 4.1 vs 2.4 months, before and after, respectively) but a subgroup
      analysis revealed that the impact was limited to a comparison biased by the
      selection of EC. After a positive EC opinion, there was no difference before and
      after MD-CTA in the time to administrative agreement signature (median 3.6 and
      3.8 months, respectively). A trend to shortening time to closure of the whole
      submission process over the time was evident, with 58% of the applications coming
      to closure within 6 months from submission in the most recent cohort.
      CONCLUSIONS: In our experience there is reassuring evidence of a trend toward
      shortening the time spent to activate non-profit clinical trials in Italy, but
      the whole process still remains inefficient. Efforts should be made to improve
      the process, also focusing on administrative procedures.

PMID- 20686687
TI  - Mechanism of microRNA-target interaction: molecular dynamics simulations and
      thermodynamics analysis.
AB  - MicroRNAs (miRNAs) are endogenously produced approximately 21-nt riboregulators
      that associate with Argonaute (Ago) proteins to direct mRNA cleavage or repress
      the translation of complementary RNAs. Capturing the molecular mechanisms of
      miRNA interacting with its target will not only reinforce the understanding of
      underlying RNA interference but also fuel the design of more effective small
      interfering RNA strands. To address this, in the present work the RNA-bound (Ago
      miRNA, Ago-miRNA-target) and RNA-free Ago forms were analyzed by performing both
      molecular dynamics simulations and thermodynamic analysis. Based on the principal
      component analysis results of the simulation trajectories as well as the
      correlation analysis in fluctuations of residues, we discover that: 1) three
      important (PAZ, Mid and PIWI) domains exist in Argonaute which define the global
      dynamics of the protein; 2) the interdomain correlated movements are so crucial
      for the interaction of Ago-RNAs that they not only facilitate the relaxation of
      the interactions between residues surrounding the RNA binding channel but also
      induce certain conformational changes; and 3) it is just these conformational
      changes that expand the cavity of the active site and open putative pathways for
      both the substrate uptake and product release. In addition, by thermodynamic
      analysis we also discover that for both the guide RNA 5'-end recognition and the
      facilitated site-specific cleavage of the target, the presence of two metal ions
      (of Mg(2+)) plays a predominant role, and this conclusion is consistent with the
      observed enzyme catalytic cleavage activity in the ternary complex (Ago-miRNA
      mRNA). Our results find that it is the set of arginine amino acids concentrated
      in the nucleotide-binding channel in Ago, instead of the conventionally-deemed
      seed base-paring, that makes greater contributions in stabilizing the binding of
      the nucleic acids to Ago.

PMID- 20686688
TI  - Role of endoplasmic reticulum stress in alpha-TEA mediated TRAIL/DR5 death
      receptor dependent apoptosis.
AB  - BACKGROUND: Alpha-TEA (RRR-alpha-tocopherol ether-linked acetic acid analog), a
      derivative of RRR-alpha-tocopherol (vitamin E) exhibits anticancer actions in
      vitro and in vivo in variety of cancer types. The objective of this study was to
      obtain additional insights into the mechanisms involved in alpha-TEA induced
      apoptosis in human breast cancer cells. METHODOLOGY/PRINCIPAL FINDINGS: alpha-TEA
      induces endoplasmic reticulum (ER) stress as indicated by increased expression of
      CCAAT/enhancer binding protein homologous protein (CHOP) as well as by enhanced
      expression or activation of specific markers of ER stress such as glucose
      regulated protein (GRP78), phosphorylated alpha subunit of eukaryotic initiation
      factor 2 (peIF-2alpha), and spliced XBP-1 mRNA. Knockdown studies using siRNAs to
      TRAIL, DR5, JNK and CHOP as well as chemical inhibitors of ER stress and caspase
      8 showed that: i) alpha-TEA activation of DR5/caspase-8 induces an ER stress
      mediated JNK/CHOP/DR5 positive amplification loop; ii) alpha-TEA downregulation
      of c-FLIP (L) protein levels is mediated by JNK/CHOP/DR5 loop via a JNK dependent
      Itch E3 ligase ubiquitination that further serves to enhance the JNK/CHOP/DR5
      amplification loop by preventing c-FLIP's inhibition of caspase-8; and (iii)
      alpha-TEA downregulation of Bcl-2 is mediated by the ER stress dependent
      JNK/CHOP/DR5 signaling. CONCLUSION: Taken together, ER stress plays an important
      role in alpha-TEA induced apoptosis by enhancing DR5/caspase-8 pro-apoptotic
      signaling and suppressing anti-apoptotic factors c-FLIP and Bcl-2 via ER stress
      mediated JNK/CHOP/DR5/caspase-8 signaling.

PMID- 20686689
TI  - More than 1,001 problems with protein domain databases: transmembrane regions,
      signal peptides and the issue of sequence homology.
AB  - Large-scale genome sequencing gained general importance for life science because
      functional annotation of otherwise experimentally uncharacterized sequences is
      made possible by the theory of biomolecular sequence homology. Historically, the
      paradigm of similarity of protein sequences implying common structure, function
      and ancestry was generalized based on studies of globular domains. Having the
      same fold imposes strict conditions over the packing in the hydrophobic core
      requiring similarity of hydrophobic patterns. The implications of sequence
      similarity among non-globular protein segments have not been studied to the same
      extent; nevertheless, homology considerations are silently extended for them.
      This appears especially detrimental in the case of transmembrane helices (TMs)
      and signal peptides (SPs) where sequence similarity is necessarily a consequence
      of physical requirements rather than common ancestry. Thus, matching of SPs/TMs
      creates the illusion of matching hydrophobic cores. Therefore, inclusion of
      SPs/TMs into domain models can give rise to wrong annotations. More than 1001
      domains among the 10,340 models of Pfam release 23 and 18 domains of SMART
      version 6 (out of 809) contain SP/TM regions. As expected, fragment-mode HMM
      searches generate promiscuous hits limited to solely the SP/TM part among clearly
      unrelated proteins. More worryingly, we show explicit examples that the scores of
      clearly false-positive hits, even in global-mode searches, can be elevated into
      the significance range just by matching the hydrophobic runs. In the PIR
      iProClass database v3.74 using conservative criteria, we find that at least
      between 2.1% and 13.6% of its annotated Pfam hits appear unjustified for a set of
      validated domain models. Thus, false-positive domain hits enforced by SP/TM
      regions can lead to dramatic annotation errors where the hit has nothing in
      common with the problematic domain model except the SP/TM region itself. We
      suggest a workflow of flagging problematic hits arising from SP/TM-containing
      models for critical reconsideration by annotation users.

PMID- 20686690
TI  - Clioquinol inhibits zinc-triggered caspase activation in the hippocampal CA1
      region of a global ischemic gerbil model.
AB  - BACKGROUND: Excessive release of chelatable zinc from excitatory synaptic
      vesicles is involved in the pathogenesis of selective neuronal cell death
      following transient forebrain ischemia. The present study was designed to examine
      the neuroprotective effect of a membrane-permeable zinc chelator, clioquinol
      (CQ), in the CA1 region of the gerbil hippocampus after transient global
      ischemia. METHODOLOGY/PRINCIPAL FINDINGS: The common carotid arteries were
      occluded bilaterally, and CQ (10 mg/kg, i.p.) was injected into gerbils once a
      day. The zinc chelating effect of CQ was examined with TSQ fluorescence and
      autometallography. Neuronal death, the expression levels of caspases and
      apoptosis inducing factor (AIF) were evaluated using TUNEL, in situ hybridization
      and Western blotting, respectively. We were able to show for the first time that
      CQ treatment attenuates the ischemia-induced zinc accumulation in the CA1
      pyramidal neurons, accompanied by less neuronal loss in the CA1 field of the
      hippocampus after ischemia. Furthermore, the expression levels of caspase-3, -9,
      and AIF were significantly decreased in the hippocampus of CQ-treated gerbils.
      CONCLUSIONS/SIGNIFICANCE: The present study indicates that the neuroprotective
      effect of CQ is related to downregulation of zinc-triggered caspase activation in
      the hippocampal CA1 region of gerbils with global ischemia.

PMID- 20686692
TI  - Altered actin centripetal retrograde flow in physically restricted immunological
      synapses.
AB  - Antigen recognition by T cells involves large scale spatial reorganization of
      numerous receptor, adhesion, and costimulatory proteins within the T cell-antigen
      presenting cell (APC) junction. The resulting patterns can be distinctive, and
      are collectively known as the immunological synapse. Dynamical assembly of
      cytoskeletal network is believed to play an important role in driving these
      assembly processes. In one experimental strategy, the APC is replaced with a
      synthetic supported membrane. An advantage of this configuration is that solid
      structures patterned onto the underlying substrate can guide immunological
      synapse assembly into altered patterns. Here, we use mobile anti-CD3epsilon on
      the spatial-partitioned supported bilayer to ligate and trigger T cell receptor
      (TCR) in live Jurkat T cells. Simultaneous tracking of both TCR clusters and GFP
      actin speckles reveals their dynamic association and individual flow patterns.
      Actin retrograde flow directs the inward transport of TCR clusters. Flow-based
      particle tracking algorithms allow us to investigate the velocity distribution of
      actin flow field across the whole synapse, and centripetal velocity of actin flow
      decreases as it moves toward the center of synapse. Localized actin flow analysis
      reveals that, while there is no influence on actin motion from substrate patterns
      directly, velocity differences of actin are observed over physically trapped TCR
      clusters. Actin flow regains its velocity immediately after passing through
      confined TCR clusters. These observations are consistent with a dynamic and
      dissipative coupling between TCR clusters and viscoelastic actin network.

PMID- 20686691
TI  - Rad51 inhibits translocation formation by non-conservative homologous
      recombination in Saccharomyces cerevisiae.
AB  - Chromosomal translocations are a primary biological response to ionizing
      radiation (IR) exposure, and are likely to result from the inappropriate repair
      of the DNA double-strand breaks (DSBs) that are created. An abundance of
      repetitive sequences in eukaryotic genomes provides ample opportunity for such
      breaks to be repaired by homologous recombination (HR) between non-allelic
      repeats. Interestingly, in the budding yeast, Saccharomyces cerevisiae the
      central strand exchange protein, Rad51 that is required for DSB repair by gene
      conversion between unlinked repeats that conserves genomic structure also
      suppresses translocation formation by several HR mechanisms. In particular, Rad51
      suppresses translocation formation by single-strand annealing (SSA), perhaps the
      most efficient mechanism for translocation formation by HR in both yeast and
      mammalian cells. Further, the enhanced translocation formation that emerges in
      the absence of Rad51 displays a distinct pattern of genetic control, suggesting
      that this occurs by a separate mechanism. Since hypomorphic mutations in RAD51 in
      mammalian cells also reduce DSB repair by conservative gene conversion and
      stimulate non-conservative repair by SSA, this mechanism may also operate in
      humans and, perhaps contribute to the genome instability that propels the
      development of cancer.

PMID- 20686693
TI  - Plasticity of noddy parents and offspring to sea-surface temperature anomalies.
AB  - Behavioral and/or developmental plasticity is crucial for resisting the impacts
      of environmental stressors. We investigated the plasticity of adult foraging
      behavior and chick development in an offshore foraging seabird, the black noddy
      (Anous minutus), during two breeding seasons. The first season had anomalously
      high sea-surface temperatures and 'low' prey availability, while the second was a
      season of below average sea-surface temperatures and 'normal' food availability.
      During the second season, supplementary feeding of chicks was used to manipulate
      offspring nutritional status in order to mimic conditions of high prey
      availability. When sea-surface temperatures were hotter than average,
      provisioning rates were significantly and negatively impacted at the day-to-day
      scale. Adults fed chicks during this low-food season smaller meals but at the
      same rate as chicks in the unfed treatment the following season. Supplementary
      feeding of chicks during the second season also resulted in delivery of smaller
      meals by adults, but did not influence feeding rate. Chick begging and parental
      responses to cessation of food supplementation suggested smaller meals fed to
      artificially supplemented chicks resulted from a decrease in chick demands
      associated with satiation, rather than adult behavioral responses to chick
      condition. During periods of low prey abundance, chicks maintained structural
      growth while sacrificing body condition and were unable to take advantage of
      periods of high prey abundance by increasing growth rates. These results suggest
      that this species expresses limited plasticity in provisioning behavior and
      offspring development. Consequently, responses to future changes in sea-surface
      temperature and other environmental variation may be limited.

PMID- 20686694
TI  - Screening of in vivo activated genes in Enterococcus faecalis during insect and
      mouse infections and growth in urine.
AB  - Enterococcus faecalis is part of the commensal microbiota of humans and its main
      habitat is the gastrointestinal tract. Although harmless in healthy individuals,
      E. faecalis has emerged as a major cause of nosocomial infections. In order to
      better understand the transformation of a harmless commensal into a life
      threatening pathogen, we developed a Recombination-based In VivoExpression
      Technology for E. faecalis. Two R-IVET systems with different levels of
      sensitivity have been constructed in a E. faecalis V583 derivative strain and
      tested in the insect model Galleria mellonella, during growth in urine, in a
      mouse bacteremia and in a mouse peritonitis model. Our combined results led to
      the identification of 81 in vivo activated genes. Among them, the ef_3196/7
      operon was shown to be strongly induced in the insect host model. Deletion of
      this operonic structure demonstrated that this two-component system was essential
      to the E. faecalis pathogenic potential in Galleria. Gene ef_0377, induced in
      insect and mammalian models, has also been further analyzed and it has been
      demonstrated that this ankyrin-encoding gene was also involved in E. faecalis
      virulence. Thus these R-IVET screenings led to the identification of new E.
      faecalis factors implied in in vivo persistence and pathogenic potential of this
      opportunistic pathogen.

PMID- 20686695
TI  - Differential modulation of angiogenesis by erythropoiesis-stimulating agents in a
      mouse model of ischaemic retinopathy.
AB  - BACKGROUND: Erythropoiesis stimulating agents (ESAs) are widely used to treat
      anaemia but concerns exist about their potential to promote pathological
      angiogenesis in some clinical scenarios. In the current study we have assessed
      the angiogenic potential of three ESAs; epoetin delta, darbepoetin alfa and
      epoetin beta using in vitro and in vivo models. METHODOLOGY/PRINCIPAL FINDINGS:
      The epoetins induced angiogenesis in human microvascular endothelial cells at
      high doses, although darbepoetin alfa was pro-angiogenic at low-doses (1-20
      IU/ml). ESA-induced angiogenesis was VEGF-mediated. In a mouse model of ischaemia
      induced retinopathy, all ESAs induced generation of reticulocytes but only
      epoetin beta exacerbated pathological (pre-retinal) neovascularisation in
      comparison to controls (p<0.05). Only epoetin delta induced a significant
      revascularisation response which enhanced normality of the vasculature (p<0.05).
      This was associated with mobilisation of haematopoietic stem cells and their
      localisation to the retinal vasculature. Darbepoetin alfa also increased the
      number of active microglia in the ischaemic retina relative to other ESAs
      (p<0.05). Darbepoetin alfa induced retinal TNFalpha and VEGF mRNA expression
      which were up to 4 fold higher than with epoetin delta (p<0.001). CONCLUSIONS:
      This study has implications for treatment of patients as there are clear
      differences in the angiogenic potential of the different ESAs.

PMID- 20686696
TI  - TOR is a negative regulator of autophagy in Arabidopsis thaliana.
AB  - BACKGROUND: Autophagy is a protein degradation process by which cells recycle
      cytoplasmic contents under stress conditions or during senescence; a basal level
      of housekeeping autophagy also occurs under non-stressed conditions. Although a
      number of genes that function in autophagy (ATG genes) have been identified in
      plants, the upstream components that regulate the plant autophagy pathway are
      still obscure. Target of rapamycin (TOR) is a negative regulator of autophagy in
      both yeast and animals, and homologs of TOR in plants control plant growth and
      protein synthesis. However, a role for TOR in regulation of autophagy in plants
      has not been demonstrated previously. METHODOLOGY/PRINCIPAL FINDINGS: In this
      paper we used RNA interference (RNAi) to generate transgenic plants with reduced
      AtTOR transcript level. By observing monodansylcadaverine- (MDC) and GFP-AtATG8e
      labeled autophagosomes, these plants were demonstrated to have constitutive
      AtATG18a-dependent autophagy. Reverse transcriptase-PCR also showed increased
      expression of some AtATG genes in the RNAi-AtTOR plants. Unlike autophagy induced
      by starvation or salt stress, an NADPH oxidase inhibitor did not inhibit the
      constitutive autophagy in the RNAi-AtTOR lines, indicating that AtTOR is either
      downstream of or in a parallel pathway to NADPH oxidase.
      CONCLUSIONS/SIGNIFICANCE: Together, our results provide evidence that TOR is a
      negative regulator of autophagy in plants.

PMID- 20686697
TI  - Pyrethroid resistance in an Anopheles funestus population from Uganda.
AB  - BACKGROUND: The susceptibility status of Anopheles funestus to insecticides
      remains largely unknown in most parts of Africa because of the difficulty in
      rearing field-caught mosquitoes of this malaria vector. Here we report the
      susceptibility status of the An. funestus population from Tororo district in
      Uganda and a preliminary characterisation of the putative resistance mechanisms
      involved. METHODOLOGY/PRINCIPAL FINDINGS: A new forced egg laying technique used
      in this study significantly increased the numbers of field-caught females laying
      eggs and generated more than 4000 F1 adults. WHO bioassays indicated that An.
      funestus in Tororo is resistant to pyrethroids (62% mortality after 1 h exposure
      to 0.75% permethrin and 28% mortality to 0.05% deltamethrin). Suspected DDT
      resistance was also observed with 82% mortality. However this population is fully
      susceptible to bendiocarb (carbamate), malathion (organophosphate) and dieldrin
      with 100% mortality observed after exposure to each of these insecticides.
      Sequencing of a fragment of the sodium channel gene containing the 1014 codon
      conferring pyrethroid/DDT resistance in An. gambiae did not detect the L1014F kdr
      mutation but a correlation between haplotypes and resistance phenotype was
      observed indicating that mutations in other exons may be conferring the knockdown
      resistance in this species. Biochemical assays suggest that resistance in this
      population is mediated by metabolic resistance with elevated level of GSTs, P450s
      and pNPA compared to a susceptible strain of Anopheles gambiae. RT-PCR further
      confirmed the involvement of P450s with a 12-fold over-expression of CYP6P9b in
      the Tororo population compared to the fully susceptible laboratory colony FANG.
      CONCLUSION: This study represents the first report of pyrethroid/DDT resistance
      in An. funestus from East Africa. With resistance already reported in southern
      and West Africa, this indicates that resistance in An. funestus may be more
      widespread than previously assumed and therefore this should be taken into
      account for the implementation and management of vector control programs in
      Africa.

PMID- 20686698
TI  - Low-density lipoprotein receptor-related protein 1 (LRP1) mediates neuronal
      Abeta42 uptake and lysosomal trafficking.
AB  - BACKGROUND: Alzheimer's disease (AD) is characterized by the presence of early
      intraneuronal deposits of amyloid-beta 42 (Abeta42) that precede extracellular
      amyloid deposition in vulnerable brain regions. It has been hypothesized that
      endosomal/lysosomal dysfunction might be associated with the pathological
      accumulation of intracellular Abeta42 in the brain. Our previous findings suggest
      that the LDL receptor-related protein 1 (LRP1), a major receptor for
      apolipoprotein E, facilitates intraneuronal Abeta42 accumulation in mouse brain.
      However, direct evidence of neuronal endocytosis of Abeta42 through LRP1 is
      lacking. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that LRP1 endocytic
      function is required for neuronal Abeta42 uptake. Overexpression of a functional
      LRP1 minireceptor, mLRP4, increases Abeta42 uptake and accumulation in neuronal
      lysosomes. Conversely, knockdown of LRP1 expression significantly decreases
      neuronal Abeta42 uptake. Disruptions of LRP1 endocytic function by either
      clathrin knockdown or by removal of its cytoplasmic tail decreased both uptake
      and accumulation of Abeta42 in neurons. Finally, we show that LRP1-mediated
      neuronal accumulation of Abeta42 is associated with increased cellular toxicity.
      CONCLUSIONS/SIGNIFICANCE: These results demonstrate that LRP1 endocytic function
      plays an important role in the uptake and accumulation of Abeta42 in neuronal
      lysosomes. These findings emphasize the central function of LRP1 in neuronal
      Abeta metabolism.

PMID- 20686699
TI  - Telomere-mediated chromosomal instability triggers TLR4 induced inflammation and
      death in mice.
AB  - BACKGROUND: Telomeres are essential to maintain chromosomal stability. Cells
      derived from mice lacking telomerase RNA component (mTERC-/- mice) display
      elevated telomere-mediated chromosome instability. Age-dependent telomere
      shortening and associated chromosome instability reduce the capacity to respond
      to cellular stress occurring during inflammation and cancer. Inflammation is one
      of the important risk factors in cancer progression. Controlled innate immune
      responses mediated by Toll-like receptors (TLR) are required for host defense
      against infection. Our aim was to understand the role of chromosome/genome
      instability in the initiation and maintenance of inflammation.
      METHODOLOGY/PRINCIPAL FINDINGS: We examined the function of TLR4 in telomerase
      deficient mTERC-/- mice harbouring chromosome instability which did not develop
      any overt immunological disorder in pathogen-free condition or any form of
      cancers at this stage. Chromosome instability was measured in metaphase spreads
      prepared from wildtype (mTERC+/+), mTERC+/- and mTERC-/- mouse splenocytes.
      Peritoneal and/or bone marrow-derived macrophages were used to examine the
      responses of TLR4 by their ability to produce inflammatory mediators TNFalpha and
      IL6. Our results demonstrate that TLR4 is highly up-regulated in the immune cells
      derived from telomerase-null (mTERC-/-) mice and lipopolysaccharide, a natural
      ligand for TLR4 stabilises NF-kappaB binding to its promoter by down-regulating
      ATF-3 in mTERC-/- macrophages. CONCLUSIONS/SIGNIFICANCE: Our findings implied
      that background chromosome instability in the cellular level stabilises the
      action of TLR4-induced NF-kappaB action and sensitises cells to produce excess
      pro-inflammatory mediators. Chromosome/genomic instability data raises optimism
      for controlling inflammation by non-toxic TLR antagonists among high-risk groups.

PMID- 20686700
TI  - Sexual plasticity and self-fertilization in the sea anemone Aiptasia diaphana.
AB  - Traits that influence reproductive success and contribute to reproductive
      isolation in animal and plant populations are a central focus of evolutionary
      biology. In the present study we used an experimental approach to demonstrate the
      occurrence of environmental effects on sexual and asexual reproduction, and
      provide evidence for sexual plasticity and inter-clonal fertilization in
      laboratory-cultured lines of the sea anemone Aiptasia diaphana. We showed that in
      A. diaphana, both asexual reproduction by pedal laceration, and sexual
      reproduction have seasonal components. The rate of pedal laceration was ten-fold
      higher under summer photoperiod and water temperature conditions than under
      winter conditions. The onset of gametogenesis coincided with the rising water
      temperatures occurring in spring, and spawning occurred under parameters that
      emulated summer photoperiod and temperature conditions. In addition, we showed
      that under laboratory conditions, asexually produced clones derived from a single
      founder individual exhibit sexual plasticity, resulting in the development of
      both male and female individuals. Moreover, a single female founder produced not
      only males and females but also hermaphrodite individuals. We further
      demonstrated that A. diaphana can fertilize within and between clone lines,
      producing swimming planula larvae. These diverse reproductive strategies may
      explain the species success as invader of artificial marine substrates. We
      suggest that these diverse reproductive strategies, together with their unique
      evolutionary position, make Aiptasia diaphana an excellent model for studying the
      evolution of sex.

PMID- 20686701
TI  - sel-11 and cdc-42, two negative modulators of LIN-12/Notch activity in C.
      elegans.
AB  - BACKGROUND: LIN-12/Notch signaling is important for cell-cell interactions during
      development, and mutations resulting in constitutive LIN-12/Notch signaling can
      cause cancer. Loss of negative regulators of lin-12/Notch activity has the
      potential for influencing cell fate decisions during development and the genesis
      or aggressiveness of cancer. METHODOLOGY/PRINCIPAL FINDINGS: We describe two
      negative modulators of lin-12 activity in C. elegans. One gene, sel-11, was
      initially defined as a suppressor of a lin-12 hypomorphic allele; the other gene,
      cdc-42, is a well-studied Rho GTPase. Here, we show that SEL-11 corresponds to
      yeast Hrd1p and mammalian Synoviolin. We also show that cdc-42 has the genetic
      properties consistent with negative regulation of lin-12 activity during vulval
      precursor cell fate specification. CONCLUSIONS/SIGNIFICANCE: Our results
      underscore the multiplicity of negative regulatory mechanisms that impact on lin
      12/Notch activity and suggest novel mechanisms by which constitutive lin-12/Notch
      activity might be exacerbated in cancer.

PMID- 20686702
TI  - The prepared tau exon-specific antibodies revealed distinct profiles of tau in
      CSF of the patients with Creutzfeldt-Jakob disease.
AB  - BACKGROUND: The diagnostic value of CSF tau for Creutzfeldt-Jakob disease (CJD)
      has been widely evaluated, showing a markedly disease-relative manner. However,
      the profiles of tau isoforms in CSF of CJD patients remain unknown. Here, we
      prepared the exon-specific antibodies against the peptides encoded by exon-2,
      exon-3 and exon-10 of human tau protein and evaluated the reactive profiles of
      tau in CSF samples from the patients with probable CJD. METHODOLOGY/PRINCIPAL
      FINDINGS: Sequences encoding exon-2, exon-3 and exon-10 of human tau protein were
      cloned into a prokaryotic expression vector pGEX-2T. Using recombinant fusion
      proteins GST-E2, GST-E3 and GST-E10, three tau exon-specific antibodies were
      elicited. Reliable specificities of the prepared antibodies were obtained after a
      serial of purification processes, not only in recognizing the tau peptides
      encoded by exon-2, -3 and -10, but also in distinguishing six recombinant tau
      isoforms by Western blot and ELISA. Three predominant tau-specific bands were
      observed in CSF samples with the exon-specific and the commercial tau antibodies,
      respectively, showing different reactive profiles between the groups of probable
      CJD and non-CJD. A 65 KD band was detected only in the CSF samples from probable
      CJD patients, especially with the antibodies against exon-2 (Anti-tE2) and exon
      10 (Anit-tE10). The appearances of 65 KD band in CSF correlated well with
      positive 14-3-3 in CSF and typical abnormality in EEG. Such band was not observed
      in the CSF samples of six tested genetic CJD patients. CONCLUSIONS/SIGNIFICANCE:
      Three exon-specific polyclonal antibodies were successfully prepared. Based on
      these antibodies, different CSF tau profiles in Western blots were observed
      between the groups of probable CJD and non-CJD. A disease-specific tau band
      emerged in the CSF samples from probable sporadic CJD, which may supply a new
      biomarker for screening sporadic CJD.

PMID- 20686704
TI  - 9-genes reinforce the phylogeny of holometabola and yield alternate views on the
      phylogenetic placement of Strepsiptera.
AB  - BACKGROUND: The extraordinary morphology, reproductive and developmental biology,
      and behavioral ecology of twisted wing parasites (order Strepsiptera) have
      puzzled biologists for centuries. Even today, the phylogenetic position of these
      enigmatic "insects from outer space" [1] remains uncertain and contentious.
      Recent authors have argued for the placement of Strepsiptera within or as a close
      relative of beetles (order Coleoptera), as sister group of flies (order Diptera),
      or even outside of Holometabola. METHODOLOGY/PRINCIPAL FINDINGS: Here, we combine
      data from several recent studies with new data (for a total of 9 nuclear genes
      and approximately 13 kb of aligned data for 34 taxa), to help clarify the
      phylogenetic placement of Strepsiptera. Our results unequivocally support the
      monophyly of Neuropteroidea (=Neuropterida+Coleoptera)+Strepsiptera, but recover
      Strepsiptera either derived from within polyphagan beetles (order Coleoptera), or
      in a position sister to Neuropterida. All other supra-ordinal- and ordinal-level
      relationships recovered with strong nodal support were consistent with most other
      recent studies. CONCLUSIONS/SIGNIFICANCE: These results, coupled with the recent
      proposed placement of Strepsiptera sister to Coleoptera, suggest that while the
      phylogenetic neighborhood of Strepsiptera has been identified, unequivocal
      placement to a specific branch within Neuropteroidea will require additional
      study.

PMID- 20686703
TI  - Nuclear factor-kappa B family member RelB inhibits human immunodeficiency virus-1
      Tat-induced tumor necrosis factor-alpha production.
AB  - Human Immunodeficiency Virus-1 (HIV-1)-associated neurocognitive disorder (HAND)
      is likely neuroinflammatory in origin, believed to be triggered by inflammatory
      and oxidative stress responses to cytokines and HIV protein gene products such as
      the HIV transactivator of transcription (Tat). Here we demonstrate increased
      messenger RNA for nuclear factor-kappa B (NF-kappaB) family member, transcription
      factor RelB, in the brain of doxycycline-induced Tat transgenic mice, and
      increased RelB synthesis in Tat-exposed microglial cells. Since genetic ablation
      of RelB in mice leads to multi-organ inflammation, we hypothesized that Tat
      induced, newly synthesized RelB inhibits cytokine production by microglial cells,
      possibly through the formation of transcriptionally inactive RelB/RelA complexes.
      Indeed, tumor necrosis factor-alpha (TNFalpha) production in monocytes isolated
      from RelB deficient mice was significantly higher than in monocytes isolated from
      RelB expressing controls. Moreover, RelB overexpression in microglial cells
      inhibited Tat-induced TNFalpha synthesis in a manner that involved
      transcriptional repression of the TNFalpha promoter, and increased
      phosphorylation of RelA at serine 276, a prerequisite for increased RelB/RelA
      protein interactions. The Rel-homology-domain within RelB was necessary for this
      interaction. Overexpression of RelA itself, in turn, significantly increased
      TNFalpha promoter activity, an effect that was completely blocked by RelB
      overexpression. We conclude that RelB regulates TNFalpha cytokine synthesis by
      competitive interference binding with RelA, which leads to downregulation of
      TNFalpha production. Moreover, because Tat activates both RelB and TNFalpha in
      microglia, and because Tat induces inflammatory TNFalpha synthesis via NF-kappaB,
      we posit that RelB serves as a cryoprotective, anti-inflammatory, counter
      regulatory mechanism for pathogenic NF-kappaB activation. These findings identify
      a novel regulatory pathway for controlling HIV-induced microglial activation and
      cytokine production that may have important therapeutic implications for the
      management of HAND.

PMID- 20686705
TI  - The impact of phenocopy on the genetic analysis of complex traits.
AB  - A consistent debate is ongoing on genome-wide association studies (GWAs). A key
      point is the capability to identify low-penetrance variations across the human
      genome. Among the phenomena reducing the power of these analyses, phenocopy level
      (PE) hampers very seriously the investigation of complex diseases, as well known
      in neurological disorders, cancer, and likely of primary importance in human
      ageing. PE seems to be the norm, rather than the exception, especially when
      considering the role of epigenetics and environmental factors towards phenotype.
      Despite some attempts, no recognized solution has been proposed, particularly to
      estimate the effects of phenocopies on the study planning or its analysis design.
      We present a simulation, where we attempt to define more precisely how phenocopy
      impacts on different analytical methods under different scenarios. With our
      approach the critical role of phenocopy emerges, and the more the PE level
      increases the more the initial difficulty in detecting gene-gene interactions is
      amplified. In particular, our results show that strong main effects are not
      hampered by the presence of an increasing amount of phenocopy in the study
      sample, despite progressively reducing the significance of the association, if
      the study is sufficiently powered. On the opposite, when purely epistatic effects
      are simulated, the capability of identifying the association depends on several
      parameters, such as the strength of the interaction between the polymorphic
      variants, the penetrance of the polymorphism and the alleles (minor or major)
      which produce the combined effect and their frequency in the population. We
      conclude that the neglect of the possible presence of phenocopies in complex
      traits heavily affects the analysis of their genetic data.

PMID- 20686706
TI  - Quantitative and molecular genetic analyses of mutations increasing Drosophila
      life span.
AB  - Understanding the genetic and environmental factors that affect variation in life
      span and senescence is of major interest for human health and evolutionary
      biology. Multiple mechanisms affect longevity, many of which are conserved across
      species, but the genetic networks underlying each mechanism and cross-talk
      between networks are unknown. We report the results of a screen for mutations
      affecting Drosophila life span. One third of the 1,332 homozygous P-element
      insertion lines assessed had quantitative effects on life span; mutations
      reducing life span were twice as common as mutations increasing life span. We
      confirmed 58 mutations with increased longevity, only one of which is in a gene
      previously associated with life span. The effects of the mutations increasing
      life span were highly sex-specific, with a trend towards opposite effects in
      males and females. Mutations in the same gene were associated with both increased
      and decreased life span, depending on the location and orientation of the P
      element insertion, and genetic background. We observed substantial--and sex
      specific--epistasis among a sample of ten mutations with increased life span. All
      mutations increasing life span had at least one deleterious pleiotropic effect on
      stress resistance or general health, with different patterns of pleiotropy for
      males and females. Whole-genome transcript profiles of seven of the mutant lines
      and the wild type revealed 4,488 differentially expressed transcripts, 553 of
      which were common to four or more of the mutant lines, which include genes
      previously associated with life span and novel genes implicated by this study.
      Therefore longevity has a large mutational target size; genes affecting life span
      have variable allelic effects; alleles affecting life span exhibit antagonistic
      pleiotropy and form epistatic networks; and sex-specific mutational effects are
      ubiquitous. Comparison of transcript profiles of long-lived mutations and the
      control line reveals a transcriptional signature of increased life span.

PMID- 20686707
TI  - A genome-wide analysis reveals no nuclear dobzhansky-muller pairs of determinants
      of speciation between S. cerevisiae and S. paradoxus, but suggests more complex
      incompatibilities.
AB  - The Dobzhansky-Muller (D-M) model of speciation by genic incompatibility is
      widely accepted as the primary cause of interspecific postzygotic isolation.
      Since the introduction of this model, there have been theoretical and
      experimental data supporting the existence of such incompatibilities. However,
      speciation genes have been largely elusive, with only a handful of candidate
      genes identified in a few organisms. The Saccharomyces sensu stricto yeasts,
      which have small genomes and can mate interspecifically to produce sterile
      hybrids, are thus an ideal model for studying postzygotic isolation. Among them,
      only a single D-M pair, comprising a mitochondrially targeted product of a
      nuclear gene and a mitochondrially encoded locus, has been found. Thus far, no D
      M pair of nuclear genes has been identified between any sensu stricto yeasts. We
      report here the first detailed genome-wide analysis of rare meiotic products from
      an otherwise sterile hybrid and show that no classic D-M pairs of speciation
      genes exist between the nuclear genomes of the closely related yeasts S.
      cerevisiae and S. paradoxus. Instead, our analyses suggest that more complex
      interactions, likely involving multiple loci having weak effects, may be
      responsible for their post-zygotic separation. The lack of a nuclear encoded
      classic D-M pair between these two yeasts, yet the existence of multiple loci
      that may each exert a small effect through complex interactions suggests that
      initial speciation events might not always be mediated by D-M pairs. An
      alternative explanation may be that the accumulation of polymorphisms leads to
      gamete inviability due to the activities of anti-recombination mechanisms and/or
      incompatibilities between the species' transcriptional and metabolic networks,
      with no single pair at least initially being responsible for the incompatibility.
      After such a speciation event, it is possible that one or more D-M pairs might
      subsequently arise following isolation.

PMID- 20686709
TI  - Color photographic index of fall Chinook salmon embryonic development and
      accumulated thermal units.
AB  - BACKGROUND: Knowledge of the relationship between accumulated thermal units and
      developmental stages of Chinook salmon embryos can be used to determine the
      approximate date of egg fertilization in natural redds, thus providing insight
      into oviposition timing of wild salmonids. However, few studies have documented
      time to different developmental stages of embryonic Chinook salmon and no
      reference color photographs are available. The objectives of this study were to
      construct an index relating developmental stages of hatchery-reared fall Chinook
      salmon embryos to time and temperature (e.g., degree days) and provide high
      quality color photographs of each identified developmental stage.
      METHODOLOGY/PRINCIPAL FINDINGS: Fall Chinook salmon eggs were fertilized in a
      hatchery environment and sampled approximately every 72 h post-fertilization
      until 50% hatch. Known embryonic developmental features described for sockeye
      salmon were used to describe development of Chinook salmon embryos. A thermal
      sums model was used to describe the relationship between embryonic development
      rate and water temperature. Mean water temperature was 8.0 degrees C (range; 3.9
      11.7 degrees C) during the study period. Nineteen stages of embryonic development
      were identified for fall Chinook salmon; two stages in the cleavage phase, one
      stage in the gastrulation phase, and sixteen stages in the organogenesis phase.
      The thermal sums model used in this study provided similar estimates of fall
      Chinook salmon embryonic development rate in water temperatures varying from 3.9
      11.7 degrees C (mean=8 degrees C) to those from several other studies rearing
      embryos in constant 8 degrees C water temperature. CONCLUSIONS/SIGNIFICANCE: The
      developmental index provides a reasonable description of timing to known
      developmental stages of Chinook salmon embryos and was useful in determining
      developmental stages of wild fall Chinook salmon embryos excavated from redds in
      the Columbia River. This index should prove useful to other researchers who wish
      to approximate fertilization dates of Chinook salmon eggs from natural redds,
      assuming the thermal history of embryos is known.

PMID- 20686708
TI  - Interaction and modulation of two antagonistic cell wall enzymes of mycobacteria.
AB  - Bacterial cell growth and division require coordinated cell wall hydrolysis and
      synthesis, allowing for the removal and expansion of cell wall material. Without
      proper coordination, unchecked hydrolysis can result in cell lysis. How these
      opposing activities are simultaneously regulated is poorly understood. In
      Mycobacterium tuberculosis, the resuscitation-promoting factor B (RpfB), a lytic
      transglycosylase, interacts and synergizes with Rpf-interacting protein A (RipA),
      an endopeptidase, to hydrolyze peptidoglycan. However, it remains unclear what
      governs this synergy and how it is coordinated with cell wall synthesis. Here we
      identify the bifunctional peptidoglycan-synthesizing enzyme, penicillin binding
      protein 1 (PBP1), as a RipA-interacting protein. PBP1, like RipA, localizes both
      at the poles and septa of dividing cells. Depletion of the ponA1 gene, encoding
      PBP1 in M. smegmatis, results in a severe growth defect and abnormally shaped
      cells, indicating that PBP1 is necessary for viability and cell wall stability.
      Finally, PBP1 inhibits the synergistic hydrolysis of peptidoglycan by the RipA
      RpfB complex in vitro. These data reveal a post-translational mechanism for
      regulating cell wall hydrolysis and synthesis through protein-protein
      interactions between enzymes with antagonistic functions.

PMID- 20686710
TI  - Calpain 8/nCL-2 and calpain 9/nCL-4 constitute an active protease complex, G
      calpain, involved in gastric mucosal defense.
AB  - Calpains constitute a superfamily of Ca2+-dependent cysteine proteases,
      indispensable for various cellular processes. Among the 15 mammalian calpains,
      calpain 8/nCL-2 and calpain 9/nCL-4 are predominantly expressed in the
      gastrointestinal tract and are restricted to the gastric surface mucus (pit)
      cells in the stomach. Possible functions reported for calpain 8 are in vesicle
      trafficking between ER and Golgi, and calpain 9 are implicated in suppressing
      tumorigenesis. These highlight that calpains 8 and 9 are regulated differently
      from each other and from conventional calpains and, thus, have potentially
      important, specific functions in the gastrointestinal tract. However, there is no
      direct evidence implicating calpain 8 or 9 in human disease, and their properties
      and physiological functions are currently unknown. To address their physiological
      roles, we analyzed mice with mutations in the genes for these calpains, Capn8 and
      Capn9. Capn8(-/-) and Capn9(-/-) mice were fertile, and their gastric mucosae
      appeared normal. However, both mice were susceptible to gastric mucosal injury
      induced by ethanol administration. Moreover, the Capn8(-/-) stomach showed
      significant decreases in both calpains 9 and 8, and the same was true for Capn9(
      /-). Consistent with this finding, in the wild-type stomach, calpains 8 and 9
      formed a complex we termed "G-calpain," in which both were essential for
      activity. This is the first example of a "hybrid" calpain complex. To address the
      physiological relevance of the calpain 8 proteolytic activity, we generated
      calpain 8:C105S "knock-in" (Capn8(CS/CS)) mice, which expressed a proteolytically
      inactive, but structurally intact, calpain 8. Although, unlike the Capn8(-/-)
      stomach, that of the Capn8(CS/CS) mice expressed a stable and active calpain 9,
      the mice were susceptible to ethanol-induced gastric injury. These results
      provide the first evidence that both of the gastrointestinal-tract-specific
      calpains are essential for gastric mucosal defense, and they point to G-calpain
      as a potential target for gastropathies caused by external stresses.

PMID- 20686711
TI  - Massively parallel detection of gene expression in single cells using
      subnanolitre wells.
AB  - The relationship between the expression of particular genes in cells and their
      impact on phenotypic characteristics is important for understanding how cells
      regulate responses to their environment. We have developed a microwell-based
      method to detect copies of mRNA transcripts directly from individual cells by one
      step, single-cell, reverse transcription polymerase chain reaction (RT-PCR). Our
      approach permits the detection of mRNA transcripts of interest for more than 6000
      single cells in parallel per assay with high sensitivity and specificity for
      constitutively active genes. This simple method was also combined with
      microengraving and image-based cytometry to examine the relationships between
      gene expression and cellular secretion of antibodies in a clonal population. We
      observed that most individual human B cell hybridomas transcribed a requisite
      gene for their antibodies, but only a subset of those cells secreted the
      antibody. The technique should also allow the detection of replicating
      intracellular pathogens such as retroviruses.

PMID- 20686713
TI  - Water in biological systems.

PMID- 20686712
TI  - Effects of the nature and charge of the topmost layer in layer by layer self
      assembled amperometric enzyme electrodes.
AB  - Organized layer-by-layer nanostructured amperometric enzyme electrodes with self
      contained redox polyelectrolyte mediators have shown important effects depending
      on the nature and charge of the adsorbed topmost layer. Adsorption of PVS causes
      the drop of the catalytic responses to negligible values due to hindrance in
      electron hopping and enzyme wiring.

PMID- 20686714
TI  - A photoelectrochemical device for visible light driven water splitting by a
      molecular ruthenium catalyst assembled on dye-sensitized nanostructured TiO2.
AB  - A photoelectrochemical device with a molecular Ru catalyst assembled via pH
      modified Nafion on a dye-sensitized nanostructured TiO(2) film as anode and a Pt
      foil as cathode has been successfully demonstrated to split water into O(2) and
      H(2) driven by visible light.

PMID- 20686715
TI  - Inverted regioselectivity of C-H amination: Unexpected oxidation at beta- rather
      than gamma-C-H.
AB  - A rare example of beta- over gamma-C-H selectivity during Rh-catalysed sulfamate
      ester cyclisation is presented; from derivatives of 1,6-anhydro-beta-d
      mannopyranose, five-membered sulfamidates were formed in preference to the
      typical six-membered oxathiazinane intramolecular insertion products. A 3D
      structure of sulfamate 1 helps to rationalise this unusual selectivity and
      analyses suggest that n-->sigma*(CH) interactions may be a key controlling
      factor.

PMID- 20686720
TI  - pi-Conjugated disilenes stabilized by fused-ring bulky "Rind" groups.
AB  - Recent advances in the chemistry of pi-conjugated disilenes stabilized by the
      newly developed bulky groups based on a fused-ring octa-R-substituted s
      hydrindacene skeleton (Rind groups) are described. The synthesis and
      characterization of the disilenes with various aryl substituents on the silicon
      atoms are covered. The highly co-planar pi-frameworks stabilized by the
      perpendicularly-fixed Rind groups are demonstrated by the X-ray crystallographic
      analysis. The extension of the pi-conjugation over the diaryldisilene framework
      is visualized by the photophysical properties such as the UV-vis absorption
      spectra and the distinct emission both in solution and in the solid state at an
      ambient temperature.

PMID- 20686721
TI  - Diverse reactions of sterically-protected 1,3-diphosphacyclobutane-2,4-diyls with
      hydride.
AB  - Hydride-induced elimination of resonance stabilized substituents from a
      phosphorus center of 1,3-diphosphacyclobutane-2,4-diyls leads to the formation of
      versatile cyclic phosphaallyl anions that are useful for the construction of
      various electrophile-modified biradical species.

PMID- 20686722
TI  - Rovibrational levels of HD.
AB  - The dissociation energies of all rotation-vibrational states of the molecular HD
      in the ground electronic state are calculated to a high accuracy by including
      nonadiabatic, relativistic alpha(2), and quantum electrodynamic alpha(3) effects,
      with approximate treatment of small higher order alpha(4), and finite nuclear
      size corrections. The obtained result for the ground molecular state of 36
      405.7828(10) cm(-1) is in a small disagreement with the latest most precise
      experimental value.

PMID- 20686723
TI  - Complex patterns of gene expression in human T cells during in vivo aging.
AB  - Human aging is associated with complex alterations that contribute to remodelling
      of physiological processes and ultimately manifests in loss of tissue/organ
      function. Peripheral blood T cells do not escape this phenomenon and undergo
      profound remodelling with aging. Thus, investigating the effects of aging on T
      cells transcriptomics and identifying the underlying regulatory mechanisms can be
      of extreme importance to understand the aging process in the Immune System (IS).
      To this aim, we performed an analysis of gene expression data of T cells
      collected from peripheral blood of 25 healthy human donors of different age from
      25 to more than 95 years, in order to characterize changes that occur throughout
      the entire adult lifespan. By means of microarray analysis, we observed large
      groups of genes exhibiting non-monotonic expression patterns over time: such
      behaviour, that could not be observed in typical "two-group" experiments (e.g.
      young vs. old people) highlights similarities in gene expression profiles of
      young and "successfully aged" individuals. Genes whose expression profiles change
      during lifespan were grouped into three main patterns (eigenmodes) to which
      different biological functions were significantly associated. The analysis of
      KEGG pathways to which these genes belong indicated that the biological processes
      altered in T cell aging are not only those typically associated with immune cells
      (Jak-STAT signalling, T cell receptor signalling, cytokine-cytokine receptor
      interactions, etc.) but also some not specific of immune cells, such as long-term
      depression, PPAR and mTOR signalling, glucose and glutathione metabolism,
      suggesting that T cell aging may be representative of a more generalised aging
      phenomenon. Thus, the T cell may represent a useful cellular model to study
      organismal aging. We further searched for over-represented transcription factor
      binding sites (TFBSs) in the promoter regions of genes clustered by similarity of
      their age-related patterns to evidence possible co-regulation. A comparison
      between over-representation of TFBSs and the time course of the corresponding
      transcription factor (TF) expression levels revealed that a restricted group of
      TFs may play a central role in driving aging-specific changes in gene expression
      of T cells.

PMID- 20686724
TI  - Microscopic model of carbonaceous nanoporous molecular sieves--anomalous
      transport in molecularly confined spaces.
AB  - To model the equilibrium and transport properties of carbonaceous molecular
      sieves (CMS) (i.e., carbon membranes, coals, activated carbons with ink-bottle
      pore geometry, etc.) the new microscopic turbostratic carbon pore model (TCPM) is
      developed. Analysis of experimental Gibbs excess of methane adsorption on
      Shirasagi CMS 3K-161 at 298 K indicates that investigated CMS is structurally a
      heterogonous material (i.e., it is composed of slit-shaped and turbostratic
      carbon nanopores of different sizes). The predicted absolute methane isotherm,
      total pore volume of 0.22 cm(3) g(-1), enthalpy of methane adsorption of 17.5
      18.6 kJ mol(-1) on Shirasagi CMS 3K-161 at 298 K are in good agreement with
      existing experimental and theoretical data. Applying TCPM, we model the
      equilibrium and kinetic separation of hydrogen and methane mixtures adsorbed in
      CMS turbostratic carbon nanopores at infinite dilution and 194.7, 293.2, 313.2,
      423.2, and 573.2 K. We found that near ambient temperatures one can reach
      equilibrium selectivity of methane over hydrogen (CH(4)/H(2)) of 10(2) in the
      turbostratic carbon nanopores having effective cage sizes of ~5 A. Lowering an
      operating temperature down to the dry ice one increases the equilibrium
      CH(4)/H(2) selectivity in these nanopores up to 10(3). The kinetic selectivity of
      hydrogen over several investigated fluids, including: methane, argon, xenon,
      nitrogen, and carbon dioxide at studied operating conditions does not depend on
      the size of the carbon nanopore cage. This simply means that the kinetic
      separation factor is controlled by the size of the carbon nanopore constriction.
      Taking this into account, we predicted the effective size of the carbon nanopore
      constriction of real CMS from the experimentally measured kinetic H(2)/CH(4)
      selectivities at infinite dilution. The high kinetic H(2)/CH(4) selectivity of
      10(2)-10(3) corresponds to the effective size of the carbon nanopore constriction
      of <=2.958 A (i.e., lower or equal to the collision diameter of hydrogen
      molecule). However, decreasing/increasing of the effective size of the carbon
      nanopore constriction by ~0.1-0.2 A exponentially increases/decreases kinetic
      H(2)/CH(4) separation factor. Finally, we showed that the efficiency of kinetic
      separation at 298 K and infinite dilution depends on the sigma(H(2))/sigma(X) and
      not only on sigma(H(2)) (where sigma denotes the collision diameter of hydrogen
      and the mentioned above fluids, respectively).

PMID- 20686725
TI  - A theoretical study on the spectroscopy and the radiative and non-radiative
      relaxation rate constants of the S(0)(1)A(1)-S(1)(1)A(2) vibronic transitions of
      formaldehyde.
AB  - We have carried out a close examination on the mathematical treatments and the
      first-principle computations concerning the vibronic transitions between the
      S(0)(1)A(1) and the S(1)(1)A(2) states of formaldehyde. The simulation of
      absorption spectrum was presented with peak intensities calculated according to
      vibronic-coupled transition dipole moments and Franck-Condon factors. The
      radiative and non-radiative transition rate constants from the excited to the
      ground states were calculated with formulas based on Fermi's golden rule. It is
      concluded that our simulated absorption spectrum between 300 and 360 nm, as well
      as the estimated relaxation rate constants, showed good agreements with
      experimental reports.

PMID- 20686730
TI  - Intelligent clinical training systems.

PMID- 20686731
TI  - Closing the gap between NLP research and clinical practice.

PMID- 20686732
TI  - Supporting creativity and appreciation of uncertainty in exploring geo-coded
      public health data.
AB  - BACKGROUND AND OBJECTIVES: We present a prototype visualisation tool, ADVISES
      (Adaptive Visualization for e-Science), designed to support epidemiologists and
      public health practitioners in exploring geo-coded datasets and generating
      spatial epidemiological hypotheses. The tool is designed to support creative
      thinking while providing the means for the user to evaluate the validity of the
      visualization in terms of statistical uncertainty. We present an overview of the
      application and the results of an evaluation exploring public health researchers'
      responses to maps as a new way of viewing familiar data, in particular the use of
      thematic maps with adjoining descriptive statistics and forest plots to support
      the generation and evaluation of new hypotheses. METHODS: A series of qualitative
      evaluations involved one experienced researcher asking 21 volunteers to interact
      with the system to perform a series of relatively complex, realistic map-building
      and exploration tasks, using a 'think aloud' protocol, followed by a semi
      structured interview The volunteers were academic epidemiologists and UK National
      Health Service analysts. RESULTS: All users quickly and confidently created maps,
      and went on to spend substantial amounts of time exploring and interacting with
      system, generating hypotheses about their maps. CONCLUSIONS: Our findings suggest
      that the tool is able to support creativity and statistical appreciation among
      public health professionals and epidemiologists building thematic maps. Software
      such as this, introduced appropriately, could increase the capability of existing
      personnel for generating public health intelligence.

PMID- 20686733
TI  - Identifying prevalent cases of breast cancer in the French case-mix databases.
AB  - OBJECTIVES: Little is known about cancer prevalence due to a lack of systematic
      recording of cancer patient follow-up data. To estimate the annual hospital
      prevalence of breast cancer in the general population of the Isere department
      (1.1 million inhabitants) in the Rhone-Alpes region, the second largest region in
      France (6 million inhabitants), we used the inpatient case-mix data, available in
      most European countries, to develop a method of cancer case identification.
      METHODS: A selection process was applied to the acute care hospital datasets
      among women aged 18 years or older, living in the Isere department and treated
      for breast cancer between 2004 and 2007. The first step in case selection was
      based on the national anonymous unique patient identifier. The second step
      consisted of retrieving all hospital stays for each case. The third step was
      designed to detect inconsistencies in the coding of the primary localization. An
      algorithm based on ICD-10 code for the hospital admission diagnosis was used to
      rule out hospitalizations unrelated to breast cancer. Five possible models for
      estimating prevalence were created combining selection steps with the admission
      diagnosis algorithm. RESULTS: Hospital prevalence over the four-year period
      varied from 6073 breast cancer cases for the simplest model (first selection step
      without the admission diagnosis algorithm) to 4951 when the first selection step
      was associated with the breast cancer code as admission diagnosis. The model
      combining the third selection step with a breast cancer-specific admission reason
      provided 5275 prevalent cases. CONCLUSION: The last model seems more appropriate
      for case-mix-data coding. Selecting admission diagnosis improved specificity.
      Combining all hospital stays for each patient has improved diagnostic
      sensitivity.

PMID- 20686734
TI  - Long-term correlations and complexity analysis of the heart rate variability
      signal during sleep. Comparing normal and pathologic subjects.
AB  - BACKGROUND: Physiological sleep is characterized by different cyclic phenomena,
      such as REM, nonREM phases and the Cyclic Alternating Pattern (CAP), that are
      associated to characteristic patterns in the heart rate variability (HRV) signal.
      Disruption of such rhythms due to sleep disorders, for example insomnia or apnea
      syndrome, alters the normal sleep patterns and the dynamics of the HRV recorded
      during the night. OBJECTIVES: In this paper we analyze long-term and complexity
      dynamics of the HRV signal recorded during sleep in different groups of subjects.
      The aim is to investigate whether the calculated indices are able to capture the
      different characteristics and to discriminate among the groups of subjects,
      classified according sleep disorders or cardiovascular pathologies. METHODS:
      Parameters, able to detect the fractal-like behavior of a signal and to measure
      the regularity and complexity of a time series, are calculated on the HRV signal
      acquired during the night. Different groups of subjects were analyzed: healthy
      subjects with high sleep efficiency, healthy subjects with low sleep efficiency,
      subjects affected by insomnia, heart failure patients, subjects affected by
      obstructive sleep apnea. RESULTS: The evaluated parameters show significant
      differences in the groups of subjects considered in this work. In particular
      heart failure patients have significant lower entropy and complexity values,
      whereas apnea patients show an increased irregularity when compared with normal
      subjects with high sleep efficiency. CONCLUSIONS: This work proposes indices that
      can be used as global descriptors of the dynamics of the whole night and can
      discriminate among different groups of subjects.

PMID- 20686735
TI  - Blinded sample size reestimation with negative binomial counts in superiority and
      non-inferiority trials.
AB  - BACKGROUND: In the planning of clinical trials with count outcomes such as the
      number of exacerbations in chronic obstructive pulmonary disease (COPD) often
      considerable uncertainty exists with regard to the overall event rate and the
      level of overdispersion which are both crucial for sample size calculations.
      OBJECTIVES: To develop a sample size reestimation strategy that maintains the
      blinding of the trial, controls the type I error rate and is robust against
      misspecification of the nuisance parameters in the planning phase in that the
      actual power is close to the target. METHODS: The operation characteristics of
      the developed sample size reestimation procedure are investigated in a Monte
      Carlo simulation study. RESULTS: Estimators of the overall event rate and the
      overdispersion parameter that do not require unblinding can be used to
      effectively adjust the sample size without inflating the type I error rate while
      providing power values close to the target. CONCLUSIONS: If only little
      information is available regarding the size of the overall event rate and the
      overdispersion parameter in the design phase of a trial, we recommend the use of
      a design with sample size reestimation as the one suggested here. Trials in COPD
      are expected to benefit from the proposed sample size reestimation strategy.

PMID- 20686736
TI  - Evaluating strategies for marker ranking in genome-wide association studies of
      complex traits.
AB  - BACKGROUND: Genome-wide association studies (GWAS) were highly successful in
      identifying new susceptibility loci of complex traits. Such studies usually start
      with genotyping fixed arrays of genetic markers in an initial sample. Out of
      these markers, some are selected which will be further genotyped in independent
      samples. Due to the very low a priori probability of a true positive association,
      the vast majority of all marker signals will turn out to be false positive. Thus,
      several methods to sort marker data have been proposed which will be evaluated
      here. OBJECTIVES: We compared statistical properties of ranking by p-values, q
      values, the False Positive Report Probability (FPRP) and the Bayesian False
      Discovery Probability (BFDP). METHODS: We performed simulation studies for a
      genomic region derived from GWAS data sets and calculated descriptive statistics
      as well as mean square errors with regard to the true marker ranking.
      Additionally, we applied all measures to a GWAS for early onset extreme obesity
      superimposing a priori information on candidate genes. RESULTS: Despite the
      known, more extreme probability results for traditional p-values, we observed
      that both p-values and the BFDP were more precise in reconstructing the "true"
      order of the markers in a region. In addition, the BFDP was useful to attenuate
      unexpected effects at a genome-wide scale. CONCLUSIONS: For the purpose of
      selecting markers from an initial GWAS and within the limits of this study, we
      recommend either ranking by p-values or the application of a full Bayesian
      approach for which the BFDP is a first approximation.

PMID- 20686737
TI  - Physical activity and cardiovascular mortality--disentangling the roles of work,
      fitness, and leisure.

PMID- 20686738
TI  - Well-being at work--overview and perspective.
AB  - This paper provides an overview of and perspective on the concept of well-being
      at work. Well-being is a term that reflects not only on one's health but
      satisfaction with work and life. Well-being is a summative concept that
      characterizes the quality of working lives, including occupational safety and
      health (OSH) aspects, and it may be a major determinant of productivity at the
      individual, enterprise and societal levels. Based on a review of the literature
      and a recent conference, we suggest a model linking workforce well-being,
      productivity, and population well-being. To appraise the validity of the model,
      we consider five questions: (i) is there a robust and usable definition of
      workplace well-being? (ii) have the variables that influence well-being been
      aptly described and can they be measured and used in risk assessments? (iii) what
      is the nature of evidence that well-being is linked to productivity? (iv) what is
      the state of knowledge on the effectiveness of interventions to promote workplace
      well-being? and (v) should interventions aimed at improving well-being at work
      focus on more than work-related factors?

PMID- 20686739
TI  - Development of depressive symptoms and depression during organizational change--a
      two-year follow-up study of civil servants.
AB  - OBJECTIVE: On 1 January 2007, Denmark went through a major reorganization, where
      most of its 275 municipalities and 14 counties merged into larger units. Our
      study aimed to examine the development of depressive symptoms and incident
      depression among employees affected by this organizational change. METHODS: A
      total of 685 civil servants employed in the administration of 5 municipalities
      and 2 counties participated in the study. They answered a postal questionnaire, 8
      months prior to and 16 months after the reorganization, regarding working
      conditions, psychosocial work environment factors, and depressive symptoms, based
      on the Major Depression Inventory (MDI). During the follow-up period of 2006
      2008, 295 employees had experienced a merger with other workplaces (hereafter the
      merger group), 259 had got a new job (the new job group), and 131 who experienced
      no change in workplace served as the control group. The three groups were
      compared to each other for (i) mean score of MDI and (ii) incident cases of
      depression using general linear models and logistic regression analyses,
      separately by gender. RESULTS: After adjustment of the MDI for age, occupation,
      supervisor function, and department at baseline in 2006, no significant
      differences in increase in MDI were found between the groups. The incidence of
      depression in the merger group was not significantly higher than the control
      group [women: odds ratio (OR) 1.5 (95% confidence interval [95% CI] 0.6-3.9),
      men: OR 1.7 (95% CI 0.2-18.7)], after adjustment for confounders. CONCLUSION:
      This study showed no significantly increased risk of depression or increase in
      depressive symptoms among employees exposed to organizational change as a part of
      a major local government reform.

PMID- 20686740
TI  - No short-term respiratory effects among particle-exposed employees in the
      Stockholm subway.
AB  - OBJECTIVE: Exposure to traffic-related air pollution is associated with adverse
      respiratory effects, but it is not known whether the high exposure to particles
      prevailing in the subway system may affect the respiratory system. We
      investigated airway inflammation and lung function among particle-exposed subway
      employees. METHODS: We studied 81 workers. All participants were non-smokers,
      aged 25-50 years. Three exposure groups were formed according to particulate
      matter (PM) levels obtained during an occupational hygienic investigation: 30
      platform workers [average PM(2.5) 63 ug/m(3) and DataRAM (MIE Inc, Billerica,
      Waltham, MA, USA) 182 ug/m(3)], 30 subway drivers (19 ug/m(3) and 33 ug/m(3)),
      and 21 ticket sellers (10 ug/m(3) and 13 ug/m(3)). We measured the fractional
      exhaled nitric oxide (FENO) of all workers before and after a workday. We also
      measured the peak expiratory flow (PEF) and forced expiratory volume in one
      second (FEV(1)) of platform workers and ticket sellers five times a day over two
      weeks. We calculated the arithmetic means of PEF and FEV(1) during exposed and
      unexposed time for every individual. RESULTS: There was no significant increase
      in FENO after work among platform workers, subway drivers or ticket sellers (the
      means of percentual individual change were -7%, +2% and -4% respectively). The
      averages of the ratios (exposed to unexposed time) of PEF and FEV(1) were above
      1.0 for both ticket sellers (1.016 and 1.002 respectively) and platform workers
      (1.022 and 1.005). CONCLUSIONS: Our observations do not indicate any short-term
      respiratory effects of particle exposure in the subway among the employees, with
      respect to airway inflammation or lung function.

PMID- 20686741
TI  - Food for thought ... on alternative methods for nanoparticle safety testing.

PMID- 20686742
TI  - Investigation of bone allografts representing different steps of the bone bank
      procedure using the CAM-model.
AB  - Bone grafting is commonly used to treat large bone defects. Since autografts are
      limited and frequently associated with postoperative donor morbidity, allografts
      from bone banks are often used. However, vascularisation of the allograft is
      often impaired, resulting in inadequate bone healing and functional graft
      failure. In bone bank processing, tissue is stored at -80 degree Celsius and
      subsequently subjected to a harsh multi-step cleaning and sterilisation procedure
      to prevent immune rejection or transmission of diseases. To determine which step
      of this procedure diminishes the ability of allografts to induce or promote
      vascularisation, we used the chick chorioallantoic membrane (CAM) model to
      monitor the vascular reaction to sample bone chips representing the respective
      procedural steps. The CAM model monitors the angiogenic potency of xenogeneic
      and, hence, potentially immunogeneic materials (e.g. cells, tissues, tissue
      engineered matrices). Due to the chicken embryo's lack of a fully functional
      immune system, it provides test conditions that are analogous to immunologically
      incompetent mice and is a well-suited alternative to their use. Bone chips were
      placed onto the CAM, and vascular reactions were quantified by image analysis
      after 48 h incubation. The vascular reaction was most pronounced to fresh,
      untreated bone chips that had been kept at +2 degree Celsius prior to the
      experiment. Surprisingly, storage of bone samples at -80 degree Celsius was
      sufficient to drastically reduce the vascular reaction. Consistent with this,
      samples representing different stages of the subsequent procedure showed
      similarly low vascular indices.

PMID- 20686744
TI  - The botulinum neurotoxin LD50 test - problems and solutions.
AB  - Apart from the fact that the LD50 test is generally considered a procedure
      causing severe distress, which alone should result in its immediate deletion, it
      also conflicts with the EU wide ban on cosmetic testing in animals in the case of
      Botulinum Neurotoxin (BoNT) testing. The European Pharmacopoeia monograph allows
      for the use of three alternative methods provided they are validated. However
      these alternative assays are neither implemented by the manufactures of BoNT
      products nor are they enforced by the responsible authorities, e.g. by deleting
      the LD50 from the European Pharmacopoeia. The number of animals used for the
      testing of BoNT is not officially recorded. However, data from an undercover
      investigation allow the estimation that the number of mice used in LD50tests for
      BoNT products is greater than 600,000 per year worldwide.

PMID- 20686743
TI  - Pancreatic beta cell lines and their applications in diabetes mellitus research.
AB  - During the past 30 years great effort has been put into establishing an insulin
      secreting beta cell line that retains normal regulation of insulin secretion, but
      only few of these attempts have been successful. To overcome the limited
      availability of primary beta cells and to include the principles of the 3Rs into
      the field of diabetes mellitus research, numerous investigators used X-rays or
      viruses to induce insulinomas, in vitro transformation, derivation of cells from
      transgenic mice or even non-islet cells to produce immortalised beta cell lines.
      The most widely used insulin-secreting cell lines are RIN, HIT, MIN, INS-1 and TC
      cells. These cells produce insulin and small amounts of glucagon and
      somatostatin. Some of them are only poorly responsive to glucose, others respond
      to glucose well, but their concentration-dependence curve is markedly shifted to
      higher sensitivity. Despite problems associated with beta cell cultures, these
      cell lines have provided some valuable information about physiological processes.
      However, an urgent need to establish a "normal" beta cell line of human or pig
      origin remains.

PMID- 20686745
TI  - Bad mood--bad activation? : The influence of emotions on the BOLD signal during
      finger tapping.
AB  - PURPOSE: The aim of this study was to investigate the influence of the subject's
      emotional state on the BOLD signal during simple finger tapping. MATERIAL AND
      METHODS: Twenty-nine healthy subjects participated in three functional magnetic
      resonance imaging (fMRI) sessions each. The sessions differed regarding emotional
      states, which were induced by standardized pleasant (positive condition, POS),
      unpleasant (negative condition, NEG), or neutral (neutral condition, NEU)
      pictures taken from the International Affective Picture System (IAPS) while the
      subjects performed a finger-tapping task (right index-to-thumb opposition). After
      each session, the subjects had to rate their actual mood and the pleasantness of
      the presented pictures. Furthermore, their state anxiety was assessed. Behavioral
      data were evaluated with SPSS. Functional imaging data were processed using
      statistical parametric mapping (SPM2) and were analyzed for main effects of
      emotional stimulation using an analysis of variance (ANOVA). The local maximum of
      interest was analyzed by a signal change analysis. RESULTS: Compared to the
      neutral emotional state, the positive and the negative emotional states caused a
      reduction of signal intensity changes within the primary sensorimotor hand area
      during simple finger tapping. The behavioral data indicated that the unpleasant
      pictures had a stronger effect on the emotional state than the pleasant images.
      According to these data the decrease in signal intensity change was more
      pronounced (significant; p < 0.001) in the negative condition than in the
      positive condition. CONCLUSION: This study showed that the emotional state of a
      test person is indeed influencing fMRI results and that well-balanced subjects in
      a neutral mood achieve the best fMRI results.

PMID- 20686746
TI  - Genetic and correlation analysis of silique-traits in Brassica napus L. by
      quantitative trait locus mapping.
AB  - Rapeseed yield is directly and indirectly influenced by the silique-traits, such
      as silique length (SL), seeds per silique (SS), seed weight (SW), because the
      silique is an organ which produced yield and a major photosynthesis organ as
      well. In this study, a linkage map comprising 150 simple sequence repeat and 195
      amplified fragment length polymorphism markers covering 1,759.6 cM was
      constructed in a doubled haploid population from a cross between two genotypes of
      'HZ396' and 'Y106'. In field experiments across three seasons and two locations
      in China 140 doubled haploid lines and their corresponding parents were evaluated
      for silique-traits. In total, 26 quantitative trait loci (QTL) were detected, of
      which 15 were clustered and integrated into 5 pleiotropic unique QTL by meta
      analysis. These unique QTL, which in a certain sense reflected the significant
      positive correlation between SS and SL and the significant negative correlation
      between SW and SS by the genomic location and effects of QTL detected, were
      mapped on linkage groups N7, N8 and N13. A trait-by-trait meta-analysis revealed
      5, 2 and 3 consensus QTL for SL, SS and SW, respectively. Epistatic effects
      varied according to the specific traits performed. All the epistatic interactions
      showed significant additive by additive effects while no significant epistasis by
      environment effect was identified. These findings provided a better understanding
      of the genetic factors controlling silique-traits and gained insights into the
      gene networks affecting silique-traits at QTL level in rapeseed.

PMID- 20686747
TI  - Genetic and comparative genomics mapping reveals that a powdery mildew resistance
      gene Ml3D232 originating from wild emmer co-segregates with an NBS-LRR analog in
      common wheat (Triticum aestivum L.).
AB  - Powdery mildew caused by Blumeria graminis f. sp. tritici is one of the most
      important wheat diseases worldwide and breeding for resistance using diversified
      disease resistance genes is the most promising approach to prevent outbreaks of
      powdery mildew. A powdery mildew resistance gene, originating from wild emmer
      wheat (Triticum turgidum var. dicoccoides) accessions collected from Israel, has
      been transferred into the hexaploid wheat line 3D232 through crossing and
      backcrossing. Inoculation results with 21 B. graminis f. sp. tritici races
      indicated that 3D232 is resistant to all of the powdery mildew isolates tested.
      Genetic analyses of 3D232 using an F(2) segregating population and F(3) families
      indicated that a single dominant gene, Ml3D232, confers resistance in the host
      seedling stage. By applying molecular markers and bulked segregant analysis
      (BSA), we have identified polymorphic simple sequence repeats (SSR), expressed
      sequence tags (EST) and derived sequence tagged site (STS) markers to determine
      that the Ml3D232 is located on chromosome 5BL bin 0.59-0.76. Comparative genetic
      analyses using mapped EST markers and genome sequences of rice and Brachypodium
      established co-linearity of the Ml3D232 genomic region with a 1.4 Mb genomic
      region on Brachypodium distachyon chromosome 4, and a 1.2 Mb contig located on
      the Oryza sativa chromosome 9. Our comparative approach enabled us to develop new
      EST-STS markers and to delimit the genomic region carrying Ml3D232 to a 0.8 cM
      segment that is collinear with a 558 kb region on B. distachyon. Eight EST
      markers, including an NBS-LRR analog, co-segregated with Ml3D232 to provide a
      target site for fine genetic mapping, chromosome landing and map-based cloning of
      the powdery mildew resistance gene. This newly developed common wheat germplasm
      provides broad-spectrum resistance to powdery mildew and a valuable resource for
      wheat breeding programs.

PMID- 20686748
TI  - Intensified glucose lowering in type 2 diabetes: time for a reappraisal.

PMID- 20686749
TI  - Anaerobic biodegradability and inhibitory effects of some anionic and cationic
      surfactants.
AB  - The anaerobic biodegradability and inhibitory effects on the methane production
      of three different surfactants, two anionic: sodium lauryl sulfate (SLS) and
      sodium dodecylbenzene sulfonate (SDBS), and a cationic surfactant: trialkyl
      methylammonium chloride (TMAC), were evaluated with two different anaerobic
      sludges, granular and flocculent. Five different concentrations of the
      surfactants, 5, 50, 100, 250 and 500 mg/L, were tested. SLS was biodegraded at
      concentrations of 5, 50 and 100 mg/L with flocculent sludge and at 100 and 250
      mg/L with granular sludge. However an inhibitory effect on methane production was
      observed in both sludges at 500 mg/L. The results indicate that SDBS was not
      biodegradable under anoxic conditions. TMAC was slightly degraded 50 and 100 mg/L
      with the flocculent sludge, and from 100 to 500 mg/L with the granular sludge.

PMID- 20686750
TI  - Lead concentrations of white-winged doves, Zenaida asiatica L., collected in the
      Lower Rio Grande Valley of Texas, USA.
AB  - White-winged dove (Zenaida asiatica L.) exposure to environmentally accessible
      lead is a management concern. Detectable concentrations of lead were found in 142
      (66%) of 214 white-winged doves collected in 2002 and 2003 at two wildlife
      management units in South Texas. Mean +/- SD lead concentration was 0.70 +/- 1.10
      microg/g dry weight and ranged from ND to 11.01 microg/g dw. Lead concentrations
      were significantly lower in the 2002 samples, but similar between management
      units, age, and gender. White-winged doves in South Texas are being exposed to
      lead in the environment with some reaching subclinical to toxic levels.

PMID- 20686751
TI  - Tolerance to the impairing effects of alcohol on the inhibition and activation of
      behavior.
AB  - RATIONALE: Moderate doses of alcohol impair response inhibition and slow response
      activation, and some recent work has shown that during a single dose, response
      inhibition recovers from the impairing effects of alcohol more slowly than
      response activation. Evidence for a possible lag in tolerance development to
      inhibitory versus activational mechanisms suggests that as blood alcohol
      declines, drinkers' response inhibition might continue to be impaired despite
      having an unimpaired ability to activate responses; however, this effect has not
      been studied across repeated doses. OBJECTIVE: The present study examined how
      cross-session tolerance to the impairing effects of alcohol develops
      differentially between response activation and inhibition. METHODS: Thirty-two
      healthy adults performed a cued go/no-go task that measured response activation
      and inhibition. The study tested the degree to which response activation and
      inhibition developed acute and cross-session tolerances to a moderate dose of
      alcohol (0.65 g/kg) administered twice on separate days. RESULTS: Alcohol slowed
      response activation and decreased response inhibition during both
      administrations. Response activation displayed acute tolerance to alcohol
      impairment during both administrations and cross-session tolerance from the first
      to second administration. By contrast, response inhibition showed no acute or
      cross-session tolerance. CONCLUSION: Biased recovery of response activation over
      inhibition during a single dose and as doses are repeated could contribute to
      some of the impulsive behavior commonly observed under alcohol.

PMID- 20686752
TI  - Reinforcer-dependent enhancement of operant responding in opioid-withdrawn rats.
AB  - RATIONALE AND OBJECTIVE: Opioid withdrawal increases the reinforcing
      effectiveness of the MU-opioid agonist remifentanil in rodents. The current study
      explored the selectivity of this effect by assessing operant behavior maintained
      by drug and non-drug reinforcers, remifentanil, cocaine, a palatable liquid food,
      and standard food pellets, as a function of opioid dependence and withdrawal.
      MATERIALS AND METHODS: Operant responding exhibited by nondependent, morphine
      naive groups was compared with responding exhibited by morphine-dependent and
      withdrawn groups. Dependence was established using a noncontingent morphine
      dosing procedure that has been previously verified to maintain dependence while
      allowing for daily behavioral observation during a withdrawn state. Behavior
      maintained by remifentanil (0.10-10.0 MUg/kg/infusion), cocaine (0.032-1.0
      mg/kg/infusion), a palatable liquid food reinforcer (3.2-100.0% Vanilla Ensure(r)
      and water), or food pellets was assessed in dependent and nondependent groups.
      RESULTS: Morphine withdrawal enhanced remifentanil self-administration, resulting
      in an upward and rightward shift of the descending limb of the dose-response
      curve, and increased operant responding for both food reinforcers. However,
      opioid withdrawal did not affect cocaine self-administration, nor did it affect
      responding for water. CONCLUSIONS: Enhanced operant responding observed under
      opioid-dependent and withdrawn conditions, while selective, is generalized to
      some nonopioid reinforcers.

PMID- 20686753
TI  - Electrochemical heparin sensing at liquid/liquid interfaces and polymeric
      membranes.
AB  - The monitoring of heparin and its derivatives in blood samples is important for
      the safe usage of these anticoagulants and antithrombotics in many medical
      procedures. Such an analytical task is, however, highly challenging due to their
      low therapeutic levels in the complex blood matrix, and it still relies on
      classical, indirect, clot-based assays. Here we review recent progress in the
      direct electrochemical sensing of heparin and its analogs at liquid/liquid
      interfaces and polymeric membranes. This progress has been made by utilizing the
      principle of electrochemical ion transfer at the interface between two immiscible
      electrolyte solutions (ITIES) to voltammetrically drive the interfacial transfer
      of polyanionic heparin and monitoring the resulting ionic current as a direct
      measure of heparin concentration. The sensitivity, selectivity, and
      reproducibility of the ion-transfer voltammetry of heparin are dramatically
      enhanced compared to those of traditional potentiometry. This voltammetric
      principle was successfully applied for the detection of heparin in undiluted
      blood samples, and was used to develop highly sensitive ion-selective electrodes
      based on thin polymeric membranes that are intended for analytical applications
      beyond heparin detection. The mechanism of heparin recognition and transfer at
      liquid/liquid interfaces was assessed quantitatively via sophisticated micropipet
      techniques, which aided the development of a powerful ionophore that can extract
      large heparin molecules into nonpolar organic media. Moreover, the reversible
      potentiometric detection of a lethal heparin-like contaminant in commercial
      heparin preparations was achieved through the use of a PVC membrane doped with
      methyltridodecylammonium chloride, which enables charge density dependent
      polyanion selectivity.

PMID- 20686754
TI  - Metabolic footprinting of tumorigenic and nontumorigenic uroepithelial cells
      using two-dimensional gas chromatography time-of-flight mass spectrometry.
AB  - In this study, gas chromatography mass spectrometry (GC-MS) and two-dimensional
      gas chromatography time-of-flight mass spectrometry (GCxGC-TOFMS) were employed
      for the metabolic footprinting of a pair of immortalized human uroepithelial
      cells namely HUC-1 (nontumorigenic) and HUC T-2 (tumorigenic). Both HUC-1 and HUC
      T-2 cell lines were cultivated in 1 mL of Ham's F-12 media. Subsequent to 48 h of
      incubation, 200 microL of cell culture supernatant was protein-precipitated using
      1.7 mL of methanol and an aliquot of 1.5 mL of the mixture was separated, dried,
      trimethylsilyl-derivatized, and analyzed using GC-MS and GCxGC-TOFMS. Metabolic
      profiles were analyzed using multivariate data analysis techniques to evaluate
      the changes of the metabolomes. Both GC-MS and GCxGC-TOFMS analyses showed
      distinct differences in metabolic phenotypes of the normal and tumorigenic human
      bladder cells (partial least squares-discriminant analysis (PLS-DA) of GCxGC
      TOFMS data; two latent variables, R (2) X = 0.418, R (2) Y = 0.977 and Q (2)
      (cumulative) = 0.852). Twenty metabolites were identified as being statistically
      different between the two cell types. These metabolites revealed that several key
      metabolic pathways were perturbed in tumorigenic urothelial cells as compared to
      the normal cells. Application of GCxGC-TOFMS offered several advantages compared
      to classical one-dimensional GC-MS which include enhanced chromatographic
      resolution (without increase in analytical run time), increase in sensitivity,
      improved identification of metabolites, and also separation of reagent artifacts
      from the metabolite peaks. Our results reinforced the advantages of GCxGC-TOFMS
      and the role of metabolomics in characterizing bladder cancer biology using in
      vitro cell culture models.

PMID- 20686755
TI  - In situ evaluation of chromium-DNA damage using a DNA-electrochemical biosensor.
AB  - The in situ evaluation of the direct interaction of chromium species with double
      stranded DNA (dsDNA) was studied using differential pulse voltammetry at a glassy
      carbon electrode. The DNA damage was electrochemically detected following the
      changes in the oxidation peaks of guanosine and adenosine bases. The results
      obtained revealed the interaction with dsDNA of the Cr(IV) and Cr(V) reactive
      intermediates of Cr(III) oxidation by O(2) dissolved in the solution bound to
      dsDNA. This interaction leads to different modifications and causes oxidative
      damage in the B-DNA structure. Using polyhomonucleotides of guanine and adenine,
      it was shown that the interaction between reactive intermediates Cr(IV) and Cr(V)
      DNA causes oxidative damage and preferentially takes place at guanine-rich
      segments, leading to the formation of 8-oxoguanine, the oxidation product of
      guanine residues and a biomarker of DNA oxidative damage. The interaction of
      Cr(VI) with dsDNA causes breaking of hydrogen bonds, conformational changes, and
      unfolding of the double helix, which enables easier access of other oxidative
      agents to interact with DNA, and the occurrence of oxidative damage to DNA.

PMID- 20686756
TI  - Sensitive and selective determination of hydrazine using glassy carbon electrode
      modified with Pd nanoparticles decorated multiwalled carbon nanotubes.
AB  - A glassy carbon electrode modified with palladium nanoparticles decorated
      multiwalled carbon nanotubes (GCE/nanoPd-MWCNTs) was fabricated. Incorporation of
      palladium nanoparticles onto the carbon nantube surface by thermal decomposition
      of palladium acetate led to the fabrication of a sensor with a significant
      decrease in hydrazine electrooxidation potential. The sensor exhibited low
      detection limits, high sensitivity and selectivity, rapid response, and good
      stability toward hydrazine detection.

PMID- 20686758
TI  - Infrared and Raman studies on renal stones: the use of second derivative infrared
      spectra.
AB  - Urolithiasis is a very frequent illness found in Argentina; however, stone
      analysis is not routinely performed. In this work, 86 renal calculi (from cities
      of Lujan and San Antonio de Areco, State of Buenos Aires, Argentina) have been
      analyzed by infrared and Raman spectroscopies, and the results correlated with
      the main possible pathological conditions. Calcium oxalate monohydrate
      (whewellite) and mixtures of calcium oxalate monohydrate and carbonate apatite
      were the most frequent compounds found in our samples. In order to improve the
      identification of different phases present in calculi [particularly whewellite
      and weddellite (calcium oxalate dihydrate)], the second derivative spectra were
      used. The FTIR spectroscopy together with the second derivative analysis provides
      the urologist with a good method for calculi component determinations.

PMID- 20686757
TI  - Functional diversification and evolution of antifreeze proteins in the antarctic
      fish Lycodichthys dearborni.
AB  - Antifreeze proteins (AFPs) have independently evolved in many organisms. AFPs act
      by binding to ice crystals, effectively lowering the freezing point. AFPs are
      often at high copy number in a genome and diversity exists between copies. Type
      III antifreeze proteins are found in Arctic and Antarctic eel pouts, and have
      previously been shown to evolve under positive selection. Here we combine
      molecular and proteomic techniques to understand the molecular evolution and
      diversity of Type III antifreeze proteins in a single individual Antarctic fish
      Lycodichthys dearborni. Our expressed sequence tag (EST) screen reveals that at
      least seven different AFP variants are transcribed, which are ultimately
      translated into five different protein isoforms. The isoforms have identical 66
      base pair signal sequences and different numbers of subsequent ice-binding
      domains followed by a stop codon. Isoforms with one ice-binding unit (monomer),
      two units (dimer), and multiple units (multimer) were present in the EST library.
      We identify a previously uncharacterized protein dimer, providing further
      evidence that there is diversity between Type III AFP isoforms, perhaps driven by
      positive selection for greater thermal hysteresis. Proteomic analysis confirms
      that several of these isoforms are translated and present in the liver. Our
      molecular evolution study shows that paralogs have diverged under positive
      selection. We hypothesize that antifreeze protein diversity is an important
      contributor to depressing the serum freezing point.

PMID- 20686759
TI  - Electrical microcurrent to prevent conditioning film and bacterial adhesion to
      urological stents.
AB  - Long-term catheters remain a significant clinical problem in urology due to the
      high rate of bacterial colonization, infection, and encrustation. Minutes after
      insertion of a catheter, depositions of host urinary components onto the catheter
      surface form a conditioning film actively supporting the bacterial adhesion
      process. We investigated the possibility of reducing or avoiding the buildup of
      these naturally forming conditioning films and of preventing bacterial adhesion
      by applying different current densities to platinum electrodes as a possible
      catheter coating material. In this model we employed a defined environment using
      artificial urine and Proteus mirabilis. The film formation and desorption was
      analyzed by highly mass sensitive quartz crystal microbalance and surface
      sensitive atomic force microscopy. Further, we performed bacterial staining to
      assess adherence, growth, and survival on the electrodes with different current
      densities. By applying alternating microcurrent densities on platinum electrodes,
      we could produce a self regenerative surface which actively removed the
      conditioning film and significantly reduced bacterial adherence, growth, and
      survival. The results of this study could easily be adapted to a catheter design
      for clinical use.

PMID- 20686760
TI  - US as a primary tool in the work-up of malrotation.

PMID- 20686761
TI  - Decreasing the effective radiation dose in pediatric craniofacial CT by changing
      head position.
AB  - BACKGROUND: Children are exposed to ionizing radiation during pre- and post
      operative evaluation for craniofacial surgery. OBJECTIVE: The primary purpose of
      the study was to decrease effective radiation dose while preserving the
      diagnostic quality of the study. MATERIALS AND METHODS: In this prospective study
      49 children were positioned during craniofacial CT (CFCT) imaging with their neck
      fully extended into an exaggerated sniff position, parallel to the CT gantry, to
      eliminate the majority of the cervical spine and the thyroid gland from radiation
      exposure. Image-quality and effective radiation dose comparisons were made
      retrospectively in age-matched controls (n = 49). RESULTS: When compared to CT
      scans reviewed retrospectively, the prospective examinations showed a
      statistically significant decrease in z-axis length by 16% (P < 0.0001) and
      delivered a reduced effective radiation dose by 18% (P < 0.0001). The subjective
      diagnostic quality of the exams performed in the prospective arm was maintained
      despite a slight decrease in the quality of the brain windows. There was
      statistically significant improvement in the quality of the bone windows and
      three-dimensional reconstructed images. CONCLUSION: Altering the position of the
      head by extending the neck during pediatric craniofacial CT imaging statistically
      reduces the effective radiation dose while maintaining the diagnostic quality of
      the images.

PMID- 20686762
TI  - Imaging findings of pancreatoblastoma in 4 children including a case of ectopic
      pancreatoblastoma.
AB  - BACKGROUND: Pancreatoblastoma is a rare primary pancreatic neoplasm of children.
      The tumour may arise from any portion of the pancreas, but no tumour originating
      from ectopic pancreatic tissue has been reported in the English medical
      literature. OBJECTIVE: We report the radiological findings of pancreatoblastoma
      in four children, including one tumour originating from the mesentery, to our
      knowledge, reported for the first time. MATERIALS AND METHODS: Four children with
      pancreatoblastoma were identified at our hospital between 2000 and 2007. US and
      CT were performed in all children, with MR performed in two. Various CT and MRI
      features were evaluated including size, organ of origin, definition and quality
      of tumour margins, heterogeneity and attenuation of the mass, calcification,
      presence of ascites, adenopathy, metastases, and signal intensity on MR images.
      Complete excision was performed in all children. The diagnosis of
      pancreatoblastoma was confirmed with histopathological results. RESULTS: Our
      cases displayed some typical and atypical features of pancreatoblastoma. The
      findings of our series suggest that the majority of these tumours are large,
      heterogeneous and of low to intermediate signal intensity on T1-W images and high
      signal intensity on T2-W images. Calcifications were common on CT. All of the
      tumours had heterogeneous enhancement on CT and MR images. CONCLUSION:
      Pancreatoblastoma is a rare primary tumour of the pancreas. When a large mass is
      identified in the pancreas in children that is heterogeneous in nature with
      internal calcifications, the diagnosis should be considered.

PMID- 20686763
TI  - Imaging of round pneumonia and mimics in children.
AB  - Various diseases in the pediatric age group can present as an intrathoracic
      rounded opacity on a chest radiograph. The purpose of this pictorial essay is to
      emphasize the imaging appearance of round pneumonia, an entity that occurs
      especially in the pediatric population. Additional pathologies with similar chest
      radiographic appearances are also presented. The diagnosis of round pneumonia
      should be made in children who have the typical clinical presentation along with
      chest radiographs demonstrating the characteristic findings.

PMID- 20686764
TI  - Biophysical characterization of the fluorescent protein voltage probe VSFP2.3
      based on the voltage-sensing domain of Ci-VSP.
AB  - A voltage sensitive phosphatase was discovered in the ascidian Ciona
      intestinalis. The phosphatase, Ci-VSP, contains a voltage-sensing domain
      homologous to those known from voltage-gated ion channels, but unlike ion
      channels, the voltage-sensing domain of Ci-VSP can reside in the cell membrane as
      a monomer. We fused the voltage-sensing domain of Ci-VSP to a pair of fluorescent
      reporter proteins to generate a genetically encodable voltage-sensing fluorescent
      probe, VSFP2.3. VSFP2.3 is a fluorescent voltage probe that reports changes in
      membrane potential as a FRET (fluorescence resonance energy transfer) signal.
      Here we report sensing current measurements from VSFP2.3, and show that VSFP2.3
      carries 1.2 e sensing charges, which are displaced within 1.5 ms. The sensing
      currents become faster at higher temperatures, and the voltage dependence of the
      decay time constants is temperature dependent. Neutralization of an arginine in
      S4, previously suggested to be a sensing charge, and measuring associated sensing
      currents indicate that this charge is likely to reside at the membrane-aqueous
      interface rather than within the membrane electric field. The data presented give
      us insights into the voltage-sensing mechanism of Ci-VSP, which will allow us to
      further improve the sensitivity and kinetics of the family of VSFP proteins.

PMID- 20686765
TI  - Combination radiofrequency ablation and cementoplasty for palliative treatment of
      painful neoplastic bone metastasis: experience with 53 treated lesions in 36
      patients.
AB  - OBJECTIVE: We report the safety and efficacy of combined radiofrequency ablation
      and cementoplasty in treating painful neoplastic bone lesions. MATERIALS AND
      METHODS: Fifty-three combined radiofrequency ablation and cementoplasty
      procedures were completed in 36 patients. Thirty-four vertebrae (20 lumbar, 14
      thoracic), 14 acetabulae, 3 sacra, 1 pubic symphysis, and 1 humerus were treated.
      Patient age ranged from 34 to 81 years (mean 57.6 years, SD=12.6). Primary
      malignancies included: 12 breast, 5 lung, 6 multiple myeloma, 2 prostate, 2 renal
      cell carcinoma, 1 synovial sarcoma, 1 endometrial, 1 oral squamous cell
      carcinoma, 1 lymphoma, 1 colon, 1 transitional cell carcinoma, 1 colorectal, 1
      cholangiocarcinoma, and 1 pheochromocytoma. Primary neoplasm location, pain
      levels pre- and post-procedure (as assessed using the Visual Analog Scale),
      number of radiofrequency (RF) treatments and any extravasation were documented.
      RESULTS: Combined radiofrequency ablation (RFA) and cementoplasty procedures were
      performed with 100% technical success (53 out of 53). The mean pre-procedure and
      post-procedure pain, as measured by the Visual Analog Scale (VAS), was 7.2/10 and
      3.4/10 respectively. Symptomatic complications included one case of self
      resolving transient thermal sciatic neurapraxia following RFA and
      acetabuloplasty. Two cases of transient pain following epidural leaks during
      treatment of thoracic vertebrae and breast metastases also occurred. Non
      symptomatic complications, from a variety of cases, included cement emboli to the
      lung, incidental, non-symptomatic leaks into the needle track, spinal canal,
      draining veins, disc spaces, and an intra-articular leak into the hip joint.
      CONCLUSION: Combined RFA and cementoplasty appears to be safe, practical and
      effective in the palliative treatment of painful neoplastic lesions.

PMID- 20686766
TI  - A new lateral approach to the parasacral sciatic nerve block: an anatomical
      study.
AB  - BACKGROUND: Sciatic nerve block is a commonly used technique for providing
      anesthesia and analgesia to the lower extremity. At the parasacral level, the
      nerve block is classically performed via a posterior approach in lateral
      decubitus position causing patient's discomfort. Therefore, we aimed to conduct
      an anatomical study describing a new lateral approach to the parasacral sciatic
      nerve in supine position. METHODS: The skin entry point was located on the
      vertical line through the greater trochanter (GT) at the midpoint between the
      anterior superior iliac spine (ASIS) level and the GT. The angle to the skin was
      10 degrees  dorsally oriented. According to these palpable anatomical landmarks,
      the parasacral lateral approach was simulated bilaterally in four cadavers in
      supine position. Anatomical dissection allowed assessment of the needle tip
      position with regard to the sciatic nerve. Then, to refine the anatomical
      description of this new lateral approach, 40 pelvic computer tomography (CT)
      examinations were retrospectively selected and post-processed to bilaterally
      simulate the needle route to the sciatic nerve. The skin-nerve distance, the
      optimal angle to the skin, and the sciatic nerve anteroposterior diameter at
      parasacral and ischial tuberosity levels, respectively were recorded by two
      independent readers. RESULTS: Cadaver dissection showed that the needle tip was
      placed in the vicinity of the sciatic nerve in 8/8 cases. Then, CT-simulated
      lateral approach demonstrated a mean skin-nerve distance of 128 mm (81-173), and
      a 12 degrees  dorsally oriented (5-22) optimal angle to the skin. The sciatic
      nerve anteroposterior diameter was 10 mm (7-15) at the parasacral level, and 7 mm
      (5-10) more caudally at the ischial tuberosity level. No significant intra- or
      inter-observer variability was observed. CONCLUSION: This study describes a new
      lateral approach to the parasacral sciatic nerve block in supine position. These
      anatomical results should be confirmed by further clinical studies.

PMID- 20686767
TI  - Evolution in the concept of erection anatomy.
AB  - PURPOSE: To review and to summarize the literature on anatomy and physiology of
      erection in the past three decades, especially the work done in our institution.
      METHODS: A search of the PubMed database was performed using keywords erection,
      anatomy and erectile dysfunction (ED). Relevant articles were reviewed, analyzed
      and summarized. RESULTS: Penile vascularisation and innervation vary
      substantially. Internal pudendal artery is the major source of penile blood
      supply, but a supralevator accessory pudendal artery that may originate from
      inferior vesical or obturator or external iliac arteries is not uncommon. Section
      of this artery during radical prostatectomy (RP) may adversely affect
      postoperative potency. Anastomoses between the supra and the infralevator
      arterial pathways are frequent. The cavernous nerves (CNs) contain
      parasympathetic and sympathetic nerve fibers and these nerves lie within leaves
      of the lateral endopelvic fascia. Anastomoses between the CNs and the dorsal
      nerve of the penis are common. Nitric oxide released from noradrenergic,
      noncholinergic neurotransmission of the CN and from the endothelium is the
      principal neurotransmitter-mediating penile erection. Interactions between pro
      erectile and anti-erectile neurotransmitters are not completely defined. Finally,
      medial preoptic area and paraventricular nucleus are the key structures in the
      central control of sexual function and penile erection. CONCLUSIONS: The surgical
      and functional anatomy of erection is complex. Precise knowledge of penile
      vascularisation and innervation facilitates treatment of ED especially after RP.

PMID- 20686768
TI  - Comparative effect of chlorhexidine and some mouthrinses on bacterial biofilm
      formation on titanium surface.
AB  - The aim of the present study was to evaluate the effectiveness of chlorhexidine
      digluconate (CHX) and commonly used mouthrinses to single- and poly-species
      biofilms by S. mutans, S. aureus and P. aeruginosa, on titanium discs of grade
      IV. The formation of single- and poly-species biofilms at 16.5, 40.5 and 64.5-h
      incubation on titanium surface was evaluated by plate count (CFU ml-1) before and
      after exposure to CHX and four mouthrinses (Curasept, Listerine, Meridol and
      Buccagel) and expressed as percentage of Inhibitory Activity (IA%). The
      application of the different anti-plaque formulations on biofilm can reduce the
      adhesion of bacteria to titanium surface with different degrees. The higher
      efficacy was observed for Listerine that shows IA% = 100 on the biofilm formed by
      S. mutans at 16.5 h. Log count of CFU was dependent to culture time and four
      mouthrinses for S. mutans and S. aureus, whilst was not dependent to culture time
      but to mouthrinses for P. aeruginosa. In general, the efficacy was particularly
      lesser to poly-species biofilms; no statistical differences were evidenced
      between all the mouthrinses and CHX as control group. The tested mouthrinses,
      compared to reference CHX 0.2%, have demonstrated a significant lower
      antibacterial activity than Listerine towards the experimental biofilms. This "in
      vitro" biofilm model should prove extremely useful for pre-clinical testing of
      anti-plaque agents, which inhibit biofilm formation, can prevent subsequent
      implant failure.

PMID- 20686769
TI  - The novel responses of ethambutol against Mycobacterium smegmatis mc2155 Revealed
      by proteomics analysis.
AB  - Ethambutol (EMB), one of the effective anti-mycobacterial drugs, inhibits the
      biosynthesis of mycobacterium cell wall. To elucidate the molecular mechanism of
      EMB against tuberculosis (TB), Mycobacterium smegmatis mc2155 was employed as a
      model of mycobacterial system in this study. We compared the protein profiles on
      M. smegmatis mc2155 treated by EMB and untreated using fluorescence difference
      two-dimensional gel electrophoresis (2-D DIGE). A total of 40 differential
      protein spots were selected and 22 proteins were identified by HPLC-nano ESI
      MS/MS analysis, including 16 over-expressed proteins and 6 under-expressed
      proteins. These proteins mainly affected energy metabolism, as well as synthesis
      and modification of macromolecules. The expressions of correspondent genes were
      confirmed by RT-PCR. This investigation provided some clues for searching
      potential drug targets.

PMID- 20686770
TI  - Arthritic presentation of childhood malignancy: beware of normal blood counts.
AB  - Some children with malignancy (e.g. acute lymphoblastic leukemia) who initially
      present with musculoskeletal complaints may be misdiagnosed as having a
      rheumatological disorder. In the literature, importance has been given to subtle
      changes in blood counts, which may point toward an underlying malignancy. We
      report 3 children with malignancy, who had an arthritic presentation but had
      normal blood counts at presentation. Atypical clinical pattern, significant
      nocturnal pain, pain out of proportion to joint involvement and prominent
      systemic features in these children prompted us to do a bone marrow examination
      that revealed a malignancy. Pediatricians must be aware of the arthritic
      presentation of childhood malignancy. If the clinical features point toward a
      malignancy, bone marrow examination should always be performed even if the blood
      counts are normal.

PMID- 20686771
TI  - Improved liver lesion conspicuity by increasing the flip angle during hepatocyte
      phase MR imaging.
AB  - OBJECTIVE: One of the advantages of using hepatobiliary contrast agents in liver
      MRI is the ability to acquire a delayed, "hepatocyte phase" dataset. This phase
      highlights many types of lesions as hypointense compared with the liver, because
      of the accumulation of contrast material in functioning hepatocytes and non
      retention within most lesions. METHOD: Increasing the flip angle of the T1
      weighted pulse sequence used to acquire the hepatocyte phase is a simple
      parameter change that increases the contrast-to-noise ratio of focal lesions
      compared with the hepatic parenchyma. RESULT: This technique increases the
      sensitivity for detection and conspicuity of focal liver lesions. CONCLUSION:
      High flip angle delayed hepatocyte phase imaging is a useful adjunct to standard
      enhanced MRI of the liver. It allows for better sensitivity in focal lesion
      detection, particularly for small lesions. Secondarily, this technique increases
      the conspicuity of the biliary system, which is an additional benefit of delayed
      imaging with hepatobiliary contrast agents.

PMID- 20686772
TI  - COL9A2 and COL9A3 mutations in canine autosomal recessive oculoskeletal
      dysplasia.
AB  - Oculoskeletal dysplasia segregates as an autosomal recessive trait in the
      Labrador retriever and Samoyed canine breeds, in which the causative loci have
      been termed drd1 and drd2, respectively. Affected dogs exhibit short-limbed
      dwarfism and severe ocular defects. The disease phenotype resembles human
      hereditary arthro-ophthalmopathies such as Stickler and Marshall syndromes,
      although these disorders are usually dominant. Linkage studies mapped drd1 to
      canine chromosome 24 and drd2 to canine chromosome 15. Positional candidate gene
      analysis then led to the identification of a 1-base insertional mutation in exon
      1 of COL9A3 that cosegregates with drd1 and a 1,267-bp deletion mutation in the
      5' end of COL9A2 that cosegregates with drd2. Both mutations affect the COL3
      domain of the respective gene. Northern analysis showed that RNA expression of
      the respective genes was reduced in affected retinas. These models offer
      potential for studies such as protein-protein interactions between different
      members of the collagen gene family, regulation and expression of these genes in
      retina and cartilage, and even opportunities for gene therapy.

PMID- 20686773
TI  - A 1-bp deletion in the gammaC-crystallin leads to dominant cataracts in mice.
AB  - To date around 140 genetic alleles have been identified as being responsible for
      mouse cataract pathology, including Crya, Cryb, Cryg, Maf, Pax6, Pitx3, Sox,
      Connexins, MIP, and Lim-2. We obtained a dominant cataract mouse model from a
      spontaneous mutation in the F1 hybrids of outbred strain ICR mice crossed to the
      inbred strain BALB/cJ mice. Heterozygous and homozygous mutants expressed a
      nuclear cataract in both eyes. In 8-day-old mice, histological analysis showed
      that polygon epithelial cells were in the equatorial region and cortex
      underneath, and vacuole and sponge-like degeneration were in the cortical area
      underneath the posterior lens capsule. The nucleus of the lens was a deeply
      stained pink, with the shorter fibers losing their normal arrangement. For the
      entire eye, there was a blank zone in the equatorial region in 8-day-old mice;
      however, there was a certain degree of atrophy in cornea tension and retina in
      the lens in 3-month-old mice. The lens had been serious damaged in the homozygous
      mutants. For mutation mapping, heterozygous carriers were mated to wild-type
      C3H/HeJ mice, and offspring (F1 generation) with cataracts were backcrossed to
      the wild-type C3H/HeJ mice again. N2 mice with cataracts were used for
      genotyping. Using genome-wide linkage analysis, the mutation was mapped to
      chromosome 1 and the Cryg gene cluster between two markers was confirmed as the
      candidate gene. After direct sequencing the cDNA of the Cryg gene cluster, a 1-bp
      deletion was found in exon 3 of the Crygc gene, leading to a stop codon at the
      76th amino acid of exon 3 which results in production of a truncated protein in
      mutant mice (Leu160Stop). Bioinformatic analysis of the mutant gammaC-crystallin
      reveals that the COOH-terminal of the mutant protein deletes a beta-sheet, which
      affects the function of the lens proteins and leads to the development of
      cataracts.

PMID- 20686774
TI  - Signet-ring cell carcinoma of colorectum--current perspectives and molecular
      biology.
AB  - PURPOSE: Colorectal signet-ring cell carcinoma (SRCC) is rare, and very little
      detailed information on the molecular biology of the disease is available.
      METHODS: The literature on the clinical, pathological and, in particular, the
      molecular biology of this rare entity was critically reviewed. The reviewed
      articles take into account a total of 1,817 cases of SRCC, but only 143 cases
      have molecular data available. The characteristics of two patients with
      colorectal SRCC were also discussed. RESULTS: Colorectal SRCC mostly occurs in
      younger patients, is larger and has different site predilection compared with
      conventional colorectal adenocarcinoma. It can occur as one of the synchronous
      cancers in the colorectum. The cancer is usually diagnosed at advanced stages
      because of the late manifestation of symptoms, and aggressive treatment strategy
      is required. Limited reports in the literature have shown that the variant of
      colorectal cancer demonstrated a different pattern of genetic alterations of
      common growth kinase-related oncogenes (K-ras, BRAF), tumour suppressor genes
      (p53, p16), gene methylation and cell adhesion-related genes related to the
      Wingless signalling pathway (E-cadherin and beta-catenin) from conventional
      colorectal adenocarcinoma. Colorectal SRCC also showed high expression of mucin
      related genes and genes related to the gastrointestinal system. There was also a
      higher prevalence of microsatellite instability-high tumours and low Cox-2
      expression in colorectal SRCC as opposed to conventional adenocarcinoma.
      CONCLUSIONS: Colorectal SRCC has unique molecular pathological features. The
      unique molecular profiles in SRCC may provide molecular-based improvements to
      patient management in colorectal SRCC.

PMID- 20686775
TI  - Diverting stoma in rectal cancer surgery. A retrospective study of 329 patients
      from Japanese cancer centers.
AB  - BACKGROUND: A diverting stoma (DS) has been constructed for many patients with
      low anterior resection (LAR), but it is still controversial whether DS can
      prevent anastomotic leakages. The aim of this study was to investigate the risk
      factors of anastomotic leakage including DS construction, and to evaluate the
      clinical course affected by DS according to the necessity of urgent abdominal
      reoperation for anastomotic leakage. PATIENTS AND METHODS: This was a
      retrospective analysis of 329 middle or lower rectal cancer patients who
      underwent LAR with mechanical reconstruction using circular staplers. Clinical
      data were collected from five cancer centers in Japan. RESULTS: The overall
      anastomotic leakage rate was 10.0% (33 of 329). We experienced one mortality in
      this series (0.3%; 1/329). Clinical factors associated with DS construction
      included tumor location, operation time, intraoperative bleeding, lateral lymph
      node dissection, simultaneous resection of other organs, and the level of
      anastomosis, respectively. On univariate analysis, high ligation of the inferior
      mesenteric artery had a significantly high leakage rate, but not on multivariate
      analysis. DS construction had no connection with the overall leakage rate.
      Concerning the clinical course affected by DS, the frequency of urgent
      reoperation was significantly increased in patients without DS compared with
      those with DS, 11.1% and 54.2%, respectively (p = 0.04). CONCLUSIONS: LAR was the
      safe and preferred option for rectal cancer patients with very low mortality and
      an acceptable leakage rate. DS did not have a relationship with overall
      anastomotic leakage, but did seem to mitigate its consequences and reduce the
      requirement for urgent abdominal reoperation.

PMID- 20686776
TI  - Normal development of hindgut and anorectum in human embryo.
AB  - PURPOSE: The aim of the present analysis is to examine the morphological changes,
      the spatiotemporal distribution of apoptosis/proliferation in the human embryonic
      anorectum, to reveal the normal development of human anorectum, and investigate
      the possible roles of apoptosis/proliferation during anorectal development.
      MATERIALS AND METHODS: The embryos were sectioned serially and sagittally,
      stained with hematoxylin and eosin (H & E) between the third and eighth week of
      gestation, TdT-mediated dUTP-digoxigenin nick end-labeling (TUNEL) and
      proliferative cell-specific nuclear antigen (PCNA) immunohistochemical staining
      from the sixth to the eighth week. RESULTS: From the fourth to the seventh week,
      with the growth of the mesenchyme around the cloaca, the cloaca was remolded,
      subsequently, the cloacal membrane (CM) moved perpendicularly then horizontally.
      The dorsal cloaca gradually descended to the tail groove, the urorectal septum
      (URS) and the CM approximated; however, the fusion of URS with the dorsal CM was
      never observed. During the eighth week, the URS shifted ventrally and finally
      fused with the ventral CM. Moreover, from the sixth to the eighth week, the
      apoptotic cells were concentrated in the CM, the mesenchyme of terminal rectum,
      and the dorsal rectum. Meanwhile, the proliferative cells could be observed in
      the ventral mesenchyme around the cloaca, the CM, the fused tissue between the
      URS, and the ventral CM. CONCLUSIONS: During the development of human anorectum,
      it was intriguing to reveal that the URS never fused with the dorsal CM before
      dorsal CM disintegration, the normal anorectal development may depend on the
      dorsal cloaca and the dorsal CM; furthermore, the distribution of apoptosis and
      proliferation in the anorectum and ventral cloacal mesenchyme played a pivotal
      role in the formation of the anorectum.

PMID- 20686778
TI  - Endoscopic management of failed colonoscopy in clinical practice: to change
      endoscopist, instrument, or both?
AB  - BACKGROUND AND AIMS: Caecal intubation fails up to 20% of colonoscopy in clinical
      practice. We aimed to assess whether (1) in patients with a prior incomplete
      colonoscopy with a standard adult colonoscope, a subsequent caecal intubation may
      be achieved with the same instrument; (2) there are factors predicting a repeated
      unsuccessful colonoscopy; and (3) how frequently completion can be further
      achieved by shifting to a standard gastroscope. MATERIALS AND METHODS: Data of
      patients with a previously failed bowel examination referred to our community
      hospital for a further colonoscopy were reviewed. When caecal intubation still
      failed with standard colonoscope, complete colonoscopy was usually attempted by
      shifting to a gastroscope. RESULTS: Overall, 451 patients with a prior
      colonoscopy were considered. By using a standard colonoscope, caecal intubation
      rate was achieved in 285 out of 296 patients with prior complete examination and
      in 121 out of 155 patients with a prior failed colonoscopy (96.3% vs. 78.1%, p <
      .001). Caecum visualization was significantly lower when prior colonoscopy was
      stopped in the sigmoid tract as compared to any other proximal tract (65.1% vs.
      86.9%, p < .001). After a second failed examination, colonoscopy was completed in
      15 (51.7%) out of 29 cases by shifting to a standard gastroscope. No procedure
      related complications were observed in the study. CONCLUSIONS: After incomplete
      colonoscopy with a standard adult colonoscope, a further colonoscopy may be
      completed with same standard colonoscope or by using a gastroscope in the same
      session. A prior failed colonoscopy, particularly when stopped in the sigmoid
      tract, is significantly associated with a lower caecal intubation rate at second
      colonoscopy.

PMID- 20686777
TI  - Critical analysis of mucin and signet ring cell as prognostic factors in an Asian
      population of 2,764 sporadic colorectal cancers.
AB  - INTRODUCTION: Conflicting data on the clinicopathological characteristics as well
      as prognosis and survival of signet ring cell (SRC) and mucinous adenocarcinomas
      (MA) of the colorectum persist. METHODS: Consecutive patients (2,764) with
      sporadic colorectal cancer from 1999 to 2005 were evaluated. The
      clinicopathological characteristics of these patients were reviewed. Univariate
      analysis was performed, and survival curves were constructed using the Kaplan
      Meier method. Multivariate analysis assessed independent prognostic factors.
      RESULTS: The incidence of MA and SRC is 6% and 1.1%, respectively. MA and SRC
      tend to occur in patients aged <or=50 years (SRC 33%, MA 22%, ordinary
      adenocarcinomas (OA) 14%, p = 0.001) and are more commonly right-sided (MA 30%,
      SRC 27%, OA 19%, p = 0.001) than OA. SRC tend to be poorly differentiated (SRC
      77%, MA 26%, OA 6%, p < 0.0001) and have a higher risk of recurrence (SRC 40%, MA
      26%, OA 6%, p < 0.0001). SRC and MA are more likely to have locally advanced
      lesions (T3/T4; SRC 100%, MA 90%, OA 83%, p = 0.002) and lymph node metastases
      (SRC 89%, MA 61%, OA 52%, p < 0.0001) and present with an advanced stage at
      diagnosis (stage III/IV SRC 94%, MA 67%, OA 56%, p < 0.0001). SRC has poorer 5
      year cancer-specific survival (CSS; 11.1%, 95% confidence interval (CI) 0-22.9%)
      compared with MA (46.8%, 95% CI 38.6-55.0%) and OA (58.7%, 95% CI 56.5-60.9%, p <
      0.001). In a multivariate analysis, SRC is an independent poor prognostic factor
      (HR 1.9, 95% CI 1.1-3.0) but MA is not. CONCLUSION: SRC and MA demonstrate
      clinicopathologic characteristics suggestive of a different biology compared with
      OA. In our dataset, SRC has a significantly poorer CSS whereas survival rates for
      MA are similar to OA. These characteristics are similar in both Asian and Western
      studies reported. Asian reports however suggest a lower incidence of MA.

PMID- 20686779
TI  - Open dorsal vertebroplasty of the axis.
AB  - Vertebroplasty of the axis is always a challenging procedure. We report the case
      of a young, HIV-positive patient suffering from an osteolytic metastasis of the
      axis. An open dorsal vertebroplasty was performed. A leakage of the cement formed
      a new cortical bone of the massa lateralis of C2, and stabilized the C1-C2
      articulation by an arthrodesis-like effect. Durable pain relief and stabilization
      were obtained. The location of the cement, although atypical, had all desired
      effects of a conventional vertebroplasty. The intra-articular injection of cement
      into the facets for stabilization and pain relief could be considered in the
      future.

PMID- 20686780
TI  - Postmortem proteomic analysis in human amygdala of drug addicts: possible impact
      of tubulin on drug-abusing behavior.
AB  - Besides the ventral tegmental area and the nucleus accumbens as the most
      investigated brain reward structures, several reports about the relation between
      volume and activity of the amygdala and drug-seeking behavior have emphasized the
      central role of the amygdala in the etiology of addiction. Considering its
      proposed important role and the limited number of human protein expression
      studies with amygdala in drug addiction, we performed a human postmortem
      proteomic analysis of amygdala tissue obtained from 8 opiate addicts and 7
      control individuals. Results were validated by Western blot in an independent
      postmortem replication sample from 12 opiate addicts compared to 12 controls and
      12 suicide victims, as a second "control sample". Applying 2D-electrophoresis and
      MALDI-TOF-MS analysis, we detected alterations of beta-tubulin expression and
      decreased levels of the heat-shock protein HSP60 in drug addicts. Western blot
      analysis in the additional sample demonstrated significantly increased alpha- and
      beta-tubulin concentrations in the amygdala of drug abusers versus controls (P =
      0.021, 0.029) and to suicide victims (P = 0.006, 0.002). Our results suggest that
      cytoskeletal alterations in the amygdala determined by tubulin seem to be
      involved in the pathophysiology of drug addiction, probably via a relation to
      neurotransmission and cellular signaling. Moreover, the loss of neuroprotection
      against stressors by chaperons as HSP60 might also contribute to structural
      alteration in the brain of drug addicts. Although further studies have to confirm
      our results, this might be a possible pathway that may increase our understanding
      of drug addiction.

PMID- 20686781
TI  - Regulation of the initiation step of DNA replication by cyclin-dependent kinases.
AB  - Cyclin-dependent kinases (CDKs) play a central role in the regulation of cell
      cycle progression in eukaryotes. The onset of S phase, the initiation of
      chromosomal DNA replication, is a major cell cycle event that is regulated by
      CDKs. Eukaryotic chromosomal DNA replication is highly regulated and occurs as a
      two-step reaction. The first reaction, known as licensing, is essential for DNA
      replication by making cell replication competent and occurs in G1 phase. Once
      cells enter S phase, licensed chromosomes initiate DNA replication through the
      action of two conserved protein kinases, S phase-specific CDK and Cdc7-Dbf4 (or
      Dbf4-dependent kinase). Our understanding of the regulatory mechanisms of DNA
      replication in model eukaryotes has advanced considerably in the past decade. In
      this review, we overview the regulation of DNA replication in the eukaryotic cell
      cycle, focusing specifically on how CDKs regulate the initiation step of DNA
      replication.

PMID- 20686782
TI  - The prevalence and incidence of musculoskeletal symptoms among hospital
      physicians: a systematic review.
AB  - OBJECTIVE: Physicians are exposed to a range of work-related risk factors that
      may result in occupational diseases. This systematic review aims at shedding
      light on the prevalence and incidence of musculoskeletal complaints among
      hospital physicians. METHODS: A systematic literature search was performed in
      Pubmed and EMBASE (1990-2010), and methodological quality criteria were applied.
      A search was done for musculoskeletal complaints. RESULTS: Five medium-quality
      studies and three high-quality studies were included in this review. The
      definitions and assessment used in the studies for musculoskeletal complaints
      were different. In short, the frequently reported prevalence for hand and wrist
      pain was 8-33 and 0%, 17% for shoulder pain, and 9-28% for neck pain. Moreover,
      the annual prevalence of low back pain was between 33 and 68%. INTERPRETATION:
      The limited number of studies makes it difficult to draw conclusions, and the
      results should be intepreted with care. In conclusion, musculoskeletal complaints
      may be work-related complaints in hospital physicians, which need future
      attention.

PMID- 20686783
TI  - A comprehensive analysis of gene expression profiles in distal parts of the mouse
      renal tubule.
AB  - The distal parts of the renal tubule play a critical role in maintaining
      homeostasis of extracellular fluids. In this review, we present an in-depth
      analysis of microarray-based gene expression profiles available for
      microdissected mouse distal nephron segments, i.e., the distal convoluted tubule
      (DCT) and the connecting tubule (CNT), and for the cortical portion of the
      collecting duct (CCD; Zuber et al., Proc Natl Acad Sci USA 106:16523-16528,
      2009). Classification of expressed transcripts in 14 major functional gene
      categories demonstrated that all principal proteins involved in maintaining the
      salt and water balance are represented by highly abundant transcripts. However, a
      significant number of transcripts belonging, for instance, to categories of G
      protein-coupled receptors or serine/threonine kinases exhibit high expression
      levels but remain unassigned to a specific renal function. We also established a
      list of genes differentially expressed between the DCT/CNT and the CCD. This list
      is enriched by genes related to segment-specific transport functions and by
      transcription factors directing the development of the distal nephron or
      collecting ducts. Collectively, this in silico analysis provides comprehensive
      information about relative abundance and tissue specificity of the DCT/CNT and
      the CCD expressed transcripts and identifies new candidate genes for renal
      homeostasis.

PMID- 20686784
TI  - Position paper--HPV and the primary prevention of cancer; improving vaccine
      uptake by paediatricians.
AB  - A large proportion of sexually active adults are infected with the human
      papillomaviruses (HPVs). Although largely asymptomatic, some types of HPVs (HPV
      16, HPV-18) which infect the genitalia are known to cause cancers, including
      cervical cancer. Cervical cancer is an important public health concern and is the
      second most clinically important cancer to breast cancer in women aged 15-44
      years. Until recently, cervical cancer strategies focussed on screening. However,
      as adolescents become sexually active at a much younger age, the focus is on the
      use of vaccination as an effective measure to prevent progression of HPV
      infection to cancer. HPV is also involved in the aetiology of cancers of the
      anus, vagina, vulva and penis as well as genital warts and laryngeal
      papillomatosis in young children. Primary prevention through vaccination is now
      possible in Europe using either the quadrivalent HPV vaccine, Gardasil(r) (Sanofi
      Pasteur MSD), or the bivalent HPV vaccine, Cervarix(r) (GSK), which are both
      highly immunogenic, with their effects persisting for at least 5 years. HPV
      vaccines are well tolerated, with serious vaccine-related events occurring in
      less than 0.1% of patients for both vaccines. Here, we review the possibilities
      for utilising vaccination programmes alongside current cervical cancer screening
      in comprehensive cervical cancer prevention programmes. The European Academy of
      Paediatrics Scientific Working Group on Vaccination concluded that the use of HPV
      vaccines will have a significant impact in primary prevention of cancers and
      other HPV-related disease.

PMID- 20686785
TI  - Ultrastructural evidence for human mast cell-eosinophil interactions in vitro.
AB  - We have hypothesized that mast cells (MC) and eosinophils (Eos), the main
      effectors of allergy, can form an effector unit. These cells co-exist in the
      inflamed tissues during the late and chronic stages of allergy and have been
      shown to be capable of influencing each other's survival and activity via soluble
      mediators. We have recently described couples of receptor-ligands that are
      expressed on either/both of these cells and that imply a physical interaction. In
      this study, we have investigated the existence of short-term (60 min) in vitro
      interactions between human peripheral blood Eos and cord-blood-derived MC by
      transmission electron microscopy. We have found that MC and Eos adhere to each
      other; the lipid body content and the granule morphology of co-cultured MC and
      Eos, respectively, are altered, and the level of Eos peroxidase (EPO) released by
      co-cultured Eos is elevated. Moreover, the transfer of EPO from Eos to MC and
      tryptase from MC to Eos has been observed. Our results thus indicate that, when
      co-cultured, MC and Eos show signs of physical contact and of reciprocal
      activation. This is the first in vitro evidence of functional physical
      interactions between human MC and Eos, interactions that might also occur in vivo
      during allergic diseases.

PMID- 20686787
TI  - Regeneration niche differentiates functional strategies of desert woody plant
      species.
AB  - Plant communities vary dramatically in the number and relative abundance of
      species that exhibit facilitative interactions, which contributes substantially
      to variation in community structure and dynamics. Predicting species' responses
      to neighbors based on readily measurable functional traits would provide
      important insight into the factors that structure plant communities. We measured
      a suite of functional traits on seedlings of 20 species and mature plants of 54
      species of shrubs from three arid biogeographic regions. We hypothesized that
      species with different regeneration niches-those that require nurse plants for
      establishment (beneficiaries) versus those that do not (colonizers)-are
      functionally different. Indeed, seedlings of beneficiary species had lower
      relative growth rates, larger seeds and final biomass, allocated biomass toward
      roots and height at a cost to leaf mass fraction, and constructed costly, dense
      leaf and root tissues relative to colonizers. Likewise at maturity, beneficiaries
      had larger overall size and denser leaves coupled with greater water use
      efficiency than colonizers. In contrast to current hypotheses that suggest
      beneficiaries are less "stress-tolerant" than colonizers, beneficiaries exhibited
      conservative functional strategies suited to persistently dry, low light
      conditions beneath canopies, whereas colonizers exhibited opportunistic
      strategies that may be advantageous in fluctuating, open microenvironments. In
      addition, the signature of the regeneration niche at maturity indicates that
      facilitation expands the range of functional diversity within plant communities
      at all ontogenetic stages. This study demonstrates the utility of specific
      functional traits for predicting species' regeneration niches in hot deserts, and
      provides a framework for studying facilitation in other severe environments.

PMID- 20686788
TI  - Inherited fungal symbionts enhance establishment of an invasive annual grass
      across successional habitats.
AB  - Plants infected with vertically transmitted fungal endophytes carry their
      microbial symbionts with them during dispersal into new areas. Yet, whether seed
      borne endophytes enhance the host plant's ability to overcome colonisation
      barriers and to regenerate within invaded sites remains poorly understood. We
      examined how symbiosis with asexual endophytic fungi (Neotyphodium) affected
      establishment and seed loss to predators in the invasive annual grass Lolium
      multiflorum (Italian ryegrass) across contrasting successional plots. Italian
      ryegrass seeds with high and low endophyte incidence were sown into three
      communities: a 1-year-old fallow field, a 15-year-old grassland, and a 24-year
      old forest, which conformed to an old-field chronosequence in the eastern Inland
      Pampa, Argentina. We found that endophyte infection consistently increased host
      population recruitment and reproductive output. Endophyte presence also enhanced
      aerial biomass production of ryegrass in a low recruitment year but not in a high
      recruitment year, suggesting that symbiotic effects on growth performance are
      density dependent. Endophyte presence reduced seed removal by rodents, although
      differential predation may not account for the increased success of infected
      grass populations. Overall, there was no statistical evidence for an endophyte-by
      site interaction, indicating that the fungal endosymbiont benefitted host
      establishment regardless of large differences in biotic and abiotic environment
      among communities. Our results imply that hereditary endophytes may increase the
      chances for host grass species to pass various ecological filters associated with
      invasion resistance across a broad range of successional habitats.

PMID- 20686789
TI  - Ontogenetic changes in tolerance to herbivory in Arabidopsis.
AB  - Tolerance to herbivory-the ability of plants to maintain fitness despite
      herbivore damage-is expected to change during the life cycle of plants because
      the physiological mechanisms underlying tolerance to herbivory are linked to
      growth, and resource allocation to growth changes throughout ontogeny. We used
      the model plant Arabidopsis thaliana to test two hypotheses: that tolerance
      increases as plants grow, and that tolerance decreases at the onset of
      reproduction. We chose three accessions previously reported to vary for
      resistance to herbivory in order to explore whether tolerance and resistance are
      inversely related. Cabbage looper (Trichoplusia ni) larvae were allowed to feed
      on plants at either the four-leaf, six-leaf, or 1st-flower developmental stage
      until 50% of the leaf area was removed. Overall, we found a trend for increased
      tolerance with ontogenetic stage, but there were important differences among
      accessions in their response to herbivory at different stages. Tolerance did not
      decrease with the onset of flowering, nor did we find any correlation between
      resistance and tolerance levels. Three main plant traits correlated strongly with
      tolerance: stem mass, an earlier onset of reproduction and a longer fruiting
      period. This study suggests there may be considerable variation in ontogenetic
      patterns of tolerance in natural populations of A. thaliana, and warrants further
      investigations with more accessions or natural populations, and detailed
      measurements of traits purported to contribute to tolerance in our quest to
      understand the mechanisms of tolerance to herbivory.

PMID- 20686790
TI  - A validated subjective rating of display quality: the Maryland Visual Comfort
      Scale.
AB  - BACKGROUND: Minimally invasive surgery requires high-quality imaging to provide
      effective visual displays to surgeons. Whereas objective measures--pixels,
      resolution, display size, contrast ratio--are used to compare imaging systems,
      there are no tools for assessing the perceptual impact of these physical
      measures. We developed the "Maryland Visual Comfort Scale" (MVCS) to measure
      perceptual qualities in relation to an imaging system. We theorize that what the
      surgeon perceives as a high-quality image can be summarized by a scoring of seven
      characteristics related to human perception, and that image quality is not
      homogenous across a video display such that object location impacts perception
      and display quality. METHOD: We created a rating scale for seven dimensions of
      display characteristics (contrast, detail, brightness, lighting uniformity, focus
      uniformity, color, sharpness). For validation, 30 participants viewed test
      patterns and manipulated physiologic images, rating the image quality for all
      seven dimensions as well as giving an overall rating. Image ratings for contrast
      and detail dimensions were assessed across five locations on the video display.
      For ratings, two imaging systems were used, differing primarily in the 10-mm zero
      degree scope's quality: a standard scope and one taken from service for quality
      degradation. RESULTS: The rating scale was sensitive to differences in scope
      quality for all seven items in the MVCS (all p values<0.01). Significant
      differences existed between quality ratings at central and peripheral locations
      (p<0.05). CONCLUSIONS: This seven-item rating scale for assessing visual comfort
      is reliable and sensitive to scope quality differences. The scale is sensitive to
      degradation of image quality at video display edges. These seven dimensions of
      display characteristics can be refined to create a psychometric to serve as a
      composite of perceptual quality in laparoscopy.

PMID- 20686791
TI  - [Cancer pain therapy in palliative care patients: knowledge of prehospital
      emergency physicians in training. Prospective questionnaire-based investigation].
AB  - BACKGROUND: Cancer diseases are often associated with acute and chronic pain.
      Therefore, cancer pain is a symptom frequently reported by palliative care
      patients with cancer diseases. Prehospital emergency physicians may be confronted
      with exacerbation of pain in cancer patients. The aim of this study was to
      evaluate the knowledge of prehospital emergency physicians in training concerning
      cancer pain therapy. METHODS: A total of 471 prehospital emergency physicians
      received a questionnaire (period of time: 2007-2009). The questionnaire was
      prepared for the study ("mixed methods design"). Twenty-four questions concerning
      cancer pain therapy (response options: scaling, open) were designed. The
      evaluation was done descriptively according to professional experience, field
      name and experience in treating patients with cancer as well. RESULTS: A total of
      469 participants completed the questionnaire (response rate 99%). On average,
      10.8 (SD +5.7, range 2-24) questions were answered correctly. Resident physicians
      answered statistically significantly more questions correctly than consultants
      (p=0.02). Only physicians working in internal medicine achieved statistically
      significantly better results than other disciplines (e.g., surgery; p=0.01).
      Physicians with professional experience of less than 5 years answered
      statistically significantly more questions correctly (p=0.004). CONCLUSIONS: The
      results of this study verify that emergency physicians in training have
      insufficient knowledge of pain therapy and end-of-life decisions. The data of
      this investigation suggest that more attention should be paid to education on
      pain therapy and end-of-life care in medical curricula. Prehospital emergency
      physicians may thus be better prepared to provide quality care for palliative
      patients.

PMID- 20686792
TI  - A new classification for hepatocellular carcinoma with portal vein tumor
      thrombus.
AB  - BACKGROUND/PURPOSE: We aimed to correlate the survival of patients with
      hepatocellular carcinoma (HCC) with macroscopic portal vein tumor thrombus (PVTT)
      who underwent partial hepatectomy with or without portal thrombectomy with our
      PVTT classification. Currently, different staging systems for HCC are widely used
      in clinical practice. However, they lack the refinement in giving prognosis and
      guiding surgical treatment once macroscopic PVTT is present. METHODS: A
      retrospective study was carried out, in a single tertiary center, from January
      2001 to December 2004 on 441 patients who underwent partial hepatectomy with or
      without portal thrombectomy for HCC with macroscopic PVTT. Overall survival was
      examined to determine whether it was correlated with our PVTT classification, and
      with the TNM staging, Cancer of the Liver Italian Program (CLIP) scoring system,
      and the Japan Integrated Staging (JIS) scoring system. RESULTS: With our PVTT
      classification, the numbers (percentages) of patients with types I, II, III, and
      IV PVTT were 144 (32.7%), 189 (42.9%), 86 (19.5%), and 22 (5.0%), respectively.
      The corresponding 1-, 2-, and 3-year overall survival rates for types I to IV
      PVTT were 54.8, 33.9, and 26.7%; 36.4, 24.9, and 16.9%; 25.9, 12.9, and 3.7%; and
      11.1, 0, and 0%, respectively (log-rank of the survival curves P < 0.0001). Using
      the TNM system, the majority of patients were classified as stage III (n = 379 or
      85.9%). Similarly, the majority of patients (n = 388 or 88.0%) were classified as
      having CLIP scores of 2 (n = 143, or 32.4%), 3 (n = 171, or 38.8%), and 4 (n =
      74, or 16.8%). The 1-, 2-, and 3-year overall survivals for these 3 CLIP scores
      were very similar. Using the JIS score, the majority of patients (n = 372 or
      84.4%) were classified with a JIS score of 2. The 1-, 2-, and 3-year overall
      survivals of patients with a JIS score of 2 were worse than those of the patients
      with a JIS score of 1 (this was expected) as well as being worse than those with
      a JIS score of 3 (this was unexpected). Thus, the latter 3 systems of
      classification were not refined enough, and they were inadequate for stratifying
      HCC with macroscopic PVTT treated with partial hepatectomy with or without
      thrombectomy. CONCLUSIONS: In patients with HCC with macroscopic PVTT treated by
      partial hepatectomy with or without thrombectomy, our PVTT classification better
      stratified and predicted prognosis than the TNM staging, CLIP scoring system, and
      JIS scoring system, which were unrefined and inadequate for this group of
      patients.

PMID- 20686793
TI  - Volume matters: a review of procedural details of two randomised controlled
      vertebroplasty trials of 2009.
AB  - Two recent randomised controlled trials (RCT) published by the New England
      Journal of Medicine (NEJM) in 2009 comparing vertebroplasty to sham procedures
      have concluded that vertebroplasty is no more effective than injection of local
      anaesthetic at the pedicle entry point. This finding contradicts previously
      published clinical series on vertebroplasty which have shown clinical efficacy.
      The procedural details of the two RCTs are analysed specifically with regard to
      vertebral levels treated and injected polymethylmethacrylate (PMMA) volumes in an
      attempt to combine the data for assessment against the available basic science
      underpinning the effect of vertebral augmentation procedures. Neither
      investigation provides a breakdown of the vertebral levels treated in the
      original publication or in supplementary online material. Only one investigation
      provides information on fill volumes with an overall average fill volume of 2.8
      +/- 1.2 ml SD. The available basic science indicates a minimum fill volume of 13
      16% of the vertebral body volume to be necessary for a relevant biomechanical
      effect on restoration of vertebral strength. The most commonly treated vertebrae
      of the thoracolumbar junction have an anatomical vertebral body volume of ~30 ml.
      An effective fill would require a minimum of ~4 ml PMMA. Anatomical volumes and
      required fill volumes increase towards the lower lumbar spine. According to the
      available basic science, only vertebrae of the upper to mid thoracic spine could
      reasonably have received a biomechanically effective fill with the declared
      average volume of 2.8 +/- 1.2 ml SD. The available data of the NEJM publications
      strongly indicates that the treatment arm includes patients who were not treated
      in a reasonably effective manner. The technical information provided by the NEJM
      publications is insufficient to conclusively prove or disprove the clinical
      efficacy of vertebroplasty.

PMID- 20686794
TI  - An Egyptian case of congenital hyperinsulinism of infancy due to a novel mutation
      in KCNJ11 encoding Kir6.2 and response to octreotide.
AB  - Congenital hyperinsulinism of infancy (CHI) is a rare heterogeneous disease
      mostly attributable to mutations in the genes encoding the KATP channel subunits
      found in pancreatic beta-cells. Here, we report a child presenting at day 1 with
      persistent hyperinsulinemic hypoglycemia and who underwent open laparotomy and
      subtotal pancreatectomy with resection of tail and body of pancreas at 30 days of
      age. Normoglycemia was restored by Octreotide that was discontinued when the
      child was 7-month old. However, 3 months later Octreotide was re-administered as
      hypoglycemic attacks recurred. On follow-up, the child has adequate glycemic
      control and is thriving well with no neurodevelopmental morbidity. Genetic
      analysis revealed the novel mutation c.407G > A [p.R136H] in KCNJ11 encoding
      Kir6.2, confirming the diffuse form of CHI. This is to our knowledge the first
      reported Egyptian case of CHI due to a mutation in KCNJ11. 

PMID- 20686795
TI  - Primary yolk sac tumor of the paracavernous region.

PMID- 20686796
TI  - Time course of heme oxygenase-1 and oxidative stress after experimental
      intracerebral hemorrhage.
AB  - BACKGROUND: Heme oxygenase-1 (HO-1), the rate-limiting enzyme for heme catabolism
      and iron production, its role in intracerebral hemorrhage (ICH) is controversial.
      The study was to investigate correlations between brain oxidative injury and HO-1
      after experimental ICH. METHOD: Sprague-Dawley rats received intra-striatal
      infusions of 100 MUl autologous whole blood as ICH models. HO-1 were examined by
      immunohistochemical and reverse transcription polymerase chain reaction (RT-PCR)
      analysis. Brain oxidative stress was quantitated by malondialdehyde (MDA);
      antioxidation were measured by copper-zinc superoxide dismutase (Cu/Zn-SOD)
      activity using RT-PCR assay. RESULTS: The expression of the HO-1 upregulated and
      reached its peak at days 3 and 7 after ICH (P < 0.01). There was a significant
      increase of MDA and a top at 3-day post-ICH (P < 0.01); Cu/Zn-SOD was upregulated
      post-ICH and reached the top at day 7 (P < 0.001); HO-1 was correlated
      significantly with brain MDA content at days 7 and 14 following ICH (r = 0.435
      0.501, P < 0.001) but there is no definite correlation between them on 1 to 3
      days (P > 0.05); conversely, HO-1 was correlated significantly with Cu/Zn-SOD on
      1 to 3 days after ICH (r = 0.433-0.621, P < 0.001) but there is no definite
      correlation between them at days 7 and 14 (P > 0.05). CONCLUSIONS: HO-1 has both
      antioxidant and prooxidant properties in ICH. The early upregulation of HO-1
      possibly fit with the events and be protective against oxidative stress, whereas
      its overexpression in the late stages may result in its dysfunction and be toxic.
      So it should be prudent to intervene ICH with the inhibitor/activator of HO-1.

PMID- 20686797
TI  - Secondary insults following traumatic brain injury enhance complement activation
      in the human brain and release of the tissue damage marker S100B.
AB  - OBJECT: Complement activation has been suggested to play a role in the
      development of secondary injuries following traumatic brain injury (TBI). The
      present study was initiated in order to analyze complement activation in relation
      to the primary brain injury and to secondary insults, frequently occurring
      following TBI. METHODS: Twenty patients suffering from severe TBI (Glasgow coma
      score <= 8) were included in the study. The "membrane attack complex," C5b9,
      which is the cytolytic end product of the complement system was analyzed in
      cerebrospinal fluid (CSF). The degree of brain tissue damage was assessed using
      the release of S100B and neuron-specific enolase (NSE) to the CSF and blood. The
      blood-brain barrier was assessed using the CSF/serum quotient of albumin (Q (A)).
      RESULTS: Following impact, initial peaks (0-48 h) of C5b9, S100B, and NSE with a
      concomitant loss of integrity of the blood-brain barrier were observed. Secondary
      insults at the intensive care unit were monitored. Severe secondary insults were
      paralleled by a more pronounced complement activation (C5b9 in CSF) as well as
      increased levels of S100B (measured in CSF), but not with NSE. CONCLUSION: This
      human study indicates that complement activation in the brain is triggered not
      only by the impact of trauma per se but also by the amount of secondary insults
      that frequently occur at the scene of accident as well as during treatment in the
      neurointensive care unit. Complement activation and in particular the end product
      C5b9 may in turn contribute to additional secondary brain injuries by its
      membrane destructive properties.

PMID- 20686798
TI  - Determination and analysis of complete coding sequence regions of new discovered
      human bocavirus types 2 and 3.
AB  - In this study, two human bocaviruses (HBoV), HBoV2 and HBoV3, that were detected
      previously in enteric samples were characterized genetically. Nearly complete
      genome sequences of three HBoV2 variants and one HBoV3 variant originating from
      Thailand and the UK were compared to published HBoV sequences. HBoV2 showed
      divergence from HBoV1 throughout the genome, while the HBoV3 sequence grouped
      phylogenetically with HBoV1 in the non-structural region and with HBoV2 sequences
      in the structural gene, consistent with its proposed recombinant origin. Compared
      to HBoV1 and HBoV3, HBoV2 shows substantially greater intra-species diversity,
      consistent with a longer period of human circulation.

PMID- 20686799
TI  - Anti-herpes simplex virus effects of berberine from Coptidis rhizoma, a major
      component of a Chinese herbal medicine, Ching-Wei-San.
AB  - Berberine is an alkaloid extracted from Coptidis rhizome. Among the individual
      herbal components of a Chinese herb medicine, Ching-Wei-San, Coptidis Rhizoma has
      the most potent antimicrobial activity. By high-pressure liquid chromatography,
      the quantitative analysis of berberine from 6.25-mg/mL (w/v) Coptidis rhizome
      extract or 50.00-mg/mL (w/v) Ching-Wei-San was determined to be 0.26 mg/mL. To
      explore the potential use of Ching-Wei-San against herpes simplex virus (HSV)
      infection, the cytotoxicity, anti-HSV-1 and anti-HSV-2 activity in Vero cells
      were assayed. The selectivity index of berberine was about 1.2-1.5 times higher
      than that of Coptidis rhizome extract and Ching-Wei-San. Moreover, the antiviral
      activities correspond to the content of berberine in the aqueous solution.
      Berberine may interfere with the viral replication cycle after virus penetration
      and no later than the viral DNA synthesis step, and its activities were not
      affected by the preparation processes. Berberine, the natural plants that contain
      this component, including Coptidis rhizome, and Ching-Wei-San have all shown anti
      HSV effects.

PMID- 20686800
TI  - Characterization of calmodulin binding domains in TRPV2 and TRPV5 C-tails.
AB  - The transient receptor potential channels TRPV2 and TRPV5 belong to the vanilloid
      TRP subfamily. TRPV2 is highly similar to TRPV1 and shares many common properties
      with it. TRPV5 (and also its homolog TRPV6) is a rather distinct member of the
      TRPV subfamily. It is distant for being strictly Ca(2+)-selective and features
      quite different properties from the rest of the TRPV subfamily. It is known that
      TRP channels are regulated by calmodulin in a calcium-dependent manner. In our
      study we identified a calmodulin binding site on the C-termini of TRPV2 (654-683)
      and TRPV5 (587-616) corresponding to the consensus CaM binding motif 1-5-10. The
      R679 and K681 single mutants of TRPV2 caused a 50% decrease in binding affinity
      and a double mutation of K661/K664 of the same peptide lowered the binding
      affinity by up to 75%. A double mutation of R606/K607 and triple mutation of
      R594/R606/R610 in TRPV5 C-terminal peptide resulted in the total loss of binding
      affinity to calmodulin. These results demonstrate that the TRPV2 C-tail and TRPV5
      C-tail contain calmodulin binding sites and that the basic residues are strongly
      involved in TRP channel binding to calmodulin.

PMID- 20686801
TI  - Preliminary kinetic characterization of a copper amine oxidase from rat liver
      mitochondria matrix.
AB  - Kinetic measurements of a novel copper-dependent amine oxidase, purified from rat
      liver mitochondria matrix, were carried out using various substrates in a large
      pH (5.6-10.2) and ionic strength range (5-200 mM), in order to study the docking
      of substrates to the enzyme and, as a consequence, to verify the physicochemical
      characteristics of the active site. Relatively small changes of V(max) values
      (approx. 2.5-folds) over the substrates tested, suggest that the rate determining
      step of the catalysis is only slightly affected by amine chemical structure. In
      contrast, the strong change of K(M) and k(c)/K(M) values (approx. two orders of
      magnitude) indicates electrostatic control of the docking process, since the
      changes of K(M) and k(c)/K(M) values appear due to the presence of positively
      charged groups in the substrate molecules. These results suggest the presence in
      the enzyme active site of two negatively charged amino acid residues which seem
      to interact with positively charged groups of the substrate molecules. Analogies
      and differences with bovine serum amine oxidase are also described.

PMID- 20686802
TI  - Captopril improves osteopenia in ovariectomized rats and promotes bone formation
      in osteoblasts.
AB  - The present study was designed to investigate the effects of captopril, an
      angiotensin-converting enzyme inhibitor (ACEI), on bone loss in aged
      ovariectomized (OVX) rats and its impact on the differentiation of cultured
      primary osteoblasts. Ten-month-old female Sprague-Dawley rats were used for the
      study. After 2 months post ovariectomy (OVX), the rats were treated with
      captopril (1 or 5 mg/kg/day, respectively) for another 2 months. At endpoint,
      trabecular bone of the fourth lumbar vertebrae (L4) was undecalcified and
      examined by bone histomorphometry; the fifth lumbar vertebrae (L5) were examined
      by compression test. Primary osteoblasts were isolated from the calvaria of
      newborn rats and treated with different concentrations of captopril in a
      different durations. The content of secreted alkaline phosphatase (ALP) and mRNA
      expression of collagen I in osteoblasts were determined to demonstrate osteoblast
      bone formation. In aged rats with estrogen deficiency-induced osteopenia,
      captopril increased the trabecular area (%BV/TV) of L4 up to 33% and improved
      biomechanical properties by increasing L5 break stress and elastic modulus when
      compared to those in the OVX group (P < 0.01). Captopril showed dose-dependent
      effects on promoting the secretion of ALP and increased mRNA expression of
      collagen I in the cultured rat osteoblasts. In summary, captopril, one of the
      most widely used ACEIs, has the potential effects of improving lumbar vertebral
      bone strength in aged OVX rats and promoting osteoblast bone formation in vitro.

PMID- 20686803
TI  - Clinical risk factors for fracture among postmenopausal patients at risk for
      fracture: a historical cohort study using electronic medical record data.
AB  - Osteoporosis represents a growing health burden, but recognition and screening
      rates are low. Electronic reminders for osteoporosis have been beneficial but are
      not based on clinical risk factors. Available risk screening tools may contain
      useful constructs for creating risk-based electronic medical record (EMR)
      reminders. Using a cohort study design among women >=50 years with osteoporosis
      or osteoporosis risk, we searched the EMR for five World Health Organization
      (WHO) clinical risk factors including older age, lower body mass index (BMI), low
      bone mineral density (BMD), history of fracture since age 50, and maternal
      history of osteoporosis or fracture. Rates of reporting were lower than expected
      for BMD (6.8%), personal history of fracture (3.5%), and maternal history of
      fracture (0.3%). Despite the limitations, the EMR data were useful for
      identifying women at highest risk for fracture. Some evidence of bias in
      reporting rates was present. EMR data can be useful for identifying high fracture
      risk patients.

PMID- 20686804
TI  - Medical error in surgery.

PMID- 20686805
TI  - Antibodies against cyclic citrullinated peptides in infectious diseases--a
      systematic review.
AB  - Rheumatoid arthritis (RA) is a disease characterized by symmetrical polyarthritis
      of the large and small joints, and in the majority of patients, there is a
      presence of the rheumatoid factor and erosions in the X-ray of the joints. More
      recently, the presence of anti-cyclic citrullinated peptide antibodies (anti-CCP)
      in this disease has been described, with diagnostic and prognostic value.
      Nevertheless, these antibodies have also been described in infectious diseases.
      The aim of the present study was to make a systematic review of the presence of
      antibodies against citrullinated peptides in infectious diseases. Search was
      conducted in the MEDLINE (1966 to 2010), Cochrane, SCielo, and LILACS databases,
      using the terms: "anti-CCP, anti-MCV, and infectious diseases"; "anti-CCP, anti
      MCV, and virus"; "anti-CCP, anti-MCV, and mycobacteria"; "anti-CCP, anti-MCV, and
      tuberculosis"; "anti-CCP, anti-MCV, and leprosy"; "anti-CCP, anti-MCV, and
      leishmaniasis"; "anti-CCP, anti-MCV, and HIV"; "anti-CCP and HTLV"; "anti-CCP,
      anti-MCV, and Chagas disease"; "anti-CCP, anti-MCV, and Lyme disease", and the
      corresponding terms in Portuguese. Twenty-five publications were found, which
      dealt with anti-CCP and infection, and only one on anti-MCV and infection. Of
      these, 23 were cross-sectional and three cohort studies. Anti-CCP antibodies were
      found in various frequencies, reaching 37% in tuberculosis. In the other
      infections, it was a rare finding. In only one publication, anti-MCV was found in
      only one patient with hepatitis. Since infectious diseases are capable of running
      their course with osteoarticular symptoms, sometimes difficult to differentiate
      from RA, additional studies are necessary to define the performance of the test
      for the detection of anti-CCP antibodies in populations in which the frequency of
      such infections is high.

PMID- 20686806
TI  - Oncologic impact of anastomotic leakage after low anterior resection for rectal
      cancer.
AB  - Anastomotic leakage is a severe complication after rectal cancer surgery. This
      review article is focused in the incidence, the risk factors, the management and
      the oncologic impact of anastomotic leakage.

PMID- 20686807
TI  - Progress in rectal cancer staging and treatment.
AB  - Colorectal cancer poses a worldwide major health issue. Rectal cancer has
      somewhat distanced itself from colonic cancer as a different oncologic entity,
      due to differences in diagnosis and treatment. Several developments over the last
      years have improved screening, diagnostics, pre-operative therapy, surgical
      techniques and postoperative patient care. The multidisciplinary approach to
      rectal cancer, mainly through the co-operation of surgeons, oncologists and
      radiologists, seems to be one of the most important steps in the management of
      that disease.

PMID- 20686808
TI  - The role of hemorrhoidopexy in the management of 3rd degree hemorrhoids.
AB  - INTRODUCTION: Hemorrhoidopathy is a very common benign surgical pathology.
      Hemorrhoids are divided into 4 stages, depending on symptoms and degree of
      prolapse. Hemorrhoidopexy is a technique developed for the treatment of 3rd
      degree hemorrhoids, but its application has been extended to the treatment of 4th
      degree hemorrhoids as well. Nevertheless, recent studies identify weaknesses of
      the PPH in the treatment of 4th degree hemorrhoids. PATIENTS: One hundred and
      twenty-six consecutive patients with 3rd degree hemorrhoids underwent stapled
      hemorrhoidopexy. All procedures were performed under general anesthesia with the
      patient in lithotomy position. A phosphate enema was given to the patient 2 h
      before the procedure, and cephalosporine and metronidazole were administered at
      anesthesia induction. Most patients were discharged the day after the operation.
      All patients were reassessed at 1, 6 weeks, 6 and 12 months after the procedure.
      RESULTS: The mean operating time was 16.3 min. Of all patients, 5.8% complained
      of mild rectal pain for a post-operative period of 5-12 days, 5.8% developed post
      operative urinary retention, managed with catheterization, 13.3% experienced
      fecal urgency while 5.8% experienced gas incontinence, which subsided 2-8 weeks
      from surgery. The mean hospital stay was 1.2 days. Most patients returned to
      daily activities within 2-5 days. Ninety-five percent of patients returned for
      their follow-up visits. Recurrence of the disease occurred in 8 patients (6.6%).
      It was managed conservatively in 2 patients, 3 underwent redo hemorrhoidopexy and
      3 underwent classic hemorrhoidectomy. CONCLUSION: According to our results,
      stapled hemorrhoidopexy seems to be a safe, pain-free and, in the long-term,
      effective technique for the treatment of 3rd degree hemorrhoids.

PMID- 20686809
TI  - Th2 cells predominate in idiopathic steroid-sensitive nephrotic syndrome.
AB  - BACKGROUND: Various studies reported a higher incidence of allergic disorders,
      with an overreactivity of type 2 helper T-cell (Th2) immune mechanisms, in
      children with idiopathic steroid-sensitive nephrotic syndrome (ISSNS). However,
      Th2 predominance in ISSNS has not been definitively identified. To determine
      whether Th2 was predominant in children with ISSNS, we used paired samples to
      measure the type 1 helper T-cell (Th1)/Th2 ratios and serum cytokine levels
      secreted by Th1 and Th2. METHODS: We measured the Th1/Th2 ratios and levels of
      Th1- or Th2-secreted cytokines in paired samples. Fourteen children met the
      inclusion criteria: (1) ISSNS; (2) selectivity index < 0.1; (3) sera obtained in
      at least two disease phases; (4) no infection; (5) no immunosuppressants. Two
      control groups (group B, normal urinalysis; group C, nephrotic syndrome other
      than ISSNS) were included for cytokine level comparisons. Th1 and Th2 numbers
      were counted by three-color flow cytometry. Cytokine levels were measured by bead
      based assay. RESULTS: The Th1/Th2 ratio was lower in group A-1 [nephrotic-phase
      before steroid treatment (STx)] than in groups A-2 (remission-phase with STx) and
      A-3 (remission-phase without STx). Th2-secreted interleukin-5 (IL-5) levels were
      higher in group A-1 than in groups A-2 and A-3. There were no differences in IL-5
      levels between groups A-1 and C and between groups A-3 and B. CONCLUSION: Our
      results suggest that Th2 played a predominant role both in the Th1/Th2 ratio and
      in the serum IL-5 level in children with ISSNS in the nephrotic phase.

PMID- 20686810
TI  - A double-blind, randomized, multicenter, Italian study of frovatriptan versus
      rizatriptan for the acute treatment of migraine.
AB  - The objective of this study was to assess patient satisfaction with acute
      treatment of migraine with frovatriptan or rizatriptan by preference
      questionnaire. 148 subjects with a history of migraine with or without aura (IHS
      2004 criteria), with at least one migraine attack per month in the preceding 6
      months, were enrolled and randomized to frovatriptan 2.5 mg or rizatriptan 10 mg
      treating 1-3 attacks. The study had a multicenter, randomized, double-blind,
      cross-over design, with treatment periods lasting <3 months. At the end of the
      study, patients assigned preference to one of the treatments using a
      questionnaire with a score from 0 to 5 (primary endpoint). Secondary endpoints
      were pain-free and pain relief episodes at 2 h, and recurrent and sustained pain
      free episodes within 48 h. 104 of the 125 patients (83%, intention-to-treat
      population) expressed a preference for a triptan. The average preference score
      was not significantly different between frovatriptan (2.9+/-1.3) and rizatriptan
      (3.2+/-1.1). The rates of pain-free (33% frovatriptan vs. 39% rizatriptan) and
      pain relief (55 vs. 62%) episodes at 2 h were not significantly different between
      the two treatments. The rate of recurrent episodes was significantly (p<0.001)
      lower under frovatriptan (21 vs. 43% rizatriptan). No significant differences
      were observed in sustained pain-free episodes (26% frovatriptan vs. 22%
      rizatriptan). The number of patients with adverse events was not significantly
      different between rizatriptan (34) and frovatriptan (25, p=NS). The results
      suggest that frovatriptan has a similar efficacy to rizatriptan, but a more
      prolonged duration of action.

PMID- 20686811
TI  - Validation of an HR-pQCT-based homogenized finite element approach using
      mechanical testing of ultra-distal radius sections.
AB  - Osteoporotic (Colles' type) fractures of the distal radius occur relatively early
      in lifetime and could estimate risk of fracture of other, more endangered
      anatomical sites. High-resolution peripheral quantitative computed tomography (HR
      pQCT) based micro finite element (MUFE) analysis was shown to better predict
      fracture load of the distal radius than densitometry or histomorphometric
      measures. As an alternative to MUFE, homogenization-based FE (hFE) approach may
      provide at least equivalent predictive power with reduced computational needs.
      The aim of this study was to validate the hFE approach with compression tests of
      25 distal radius sections extracted at the location which is relevant in Colles'
      fractures. HR-pQCT-based input parameters of the hFE models were calibrated with
      respect to MUCT. HR-pQCT-based hFE models were then built and their ability to
      predict experimental stiffness and ultimate load was compared to those of the
      density-based parameters, histomorphometric indices and MUFE models assessed from
      the same input images. Bone mineral content was the best non-FE-based predictor
      (R (2) = 0.86) of ultimate force. Both FE methods were not only the strongest
      predictors, but provided quantitatively correct fracture loads. The calibrated
      hFE approach provided closely as strong prediction (R (2) = 0.94) as MUFE (R (2)
      = 0.95), but the former was computationally cheaper. The results of this
      validation study suggest that FE simulation could be used as an efficient and
      precise tool to predict Colles' fracture load.

PMID- 20686812
TI  - Establishment of airway eosinophilic bronchitis mouse model without
      hyperresponsiveness by ovalbumin.
AB  - Eosinophilic bronchitis (EB) is a useful tool for studying airway
      hyperresponsiveness (AHR), but an exact EB animal model is lacking. Our objective
      was to establish an EB mouse model using ovalbumin (OVA). Mice were divided into
      asthma, normal saline (NS) control and three model groups. Asthma mice were
      challenged intranasally with 200 MUg OVA. Model groups were challenged with one
      of the three OVA doses (10, 20 or 100 MUg), and NS control mice received normal
      saline. Changes in lung resistance (R(L)), serum OVA-specific immunoglobulin-E
      (IgE) and differential inflammatory cell counts in bronchoalveolar lavage fluid
      (BALF) were determined after exposure to increasing doses of methacholine (MCh).
      Lung histological sections were examined for inflammatory infiltration. R(L) in
      the 10-MUg OVA-challenged model group was not significantly different compared
      with the NS group at any MCh concentration but was significantly different
      compared with the asthma group (P < 0.01). R(L) in the other two model groups was
      intermediate between the asthma and NS groups. Serum OVA-specific IgE and
      eosinophils in BALF were increased significantly in all model and asthma groups
      compared with the NS group, but no significant differences were observed between
      model and asthma groups. Inflammatory cells were seen around bronchioles and
      capillaries in model and asthma groups but not the NS group. A mouse model of EB
      without AHR can be established by 10 MUg OVA challenge and provides a useful tool
      for studying AHR mechanisms.

PMID- 20686814
TI  - Two-year-old children copy more reliably and more often than nonhuman great apes
      in multiple observational learning tasks.
AB  - Individuals observing a proficient model can potentially benefit by copying at
      least one of the following three elements: motor movements (i.e., actions),
      goals, and results. Although several studies have investigated this issue in
      human infants, there are still very few studies that have systematically examined
      great apes' ability to spontaneously copy each of these three elements
      (particularly in comparison with human infants). We tested great apes and human
      children with eight two-target puzzle boxes-with varying levels of difficulty-to
      isolate the aspects that the various species may be more prone to copying. We
      found first trial evidence for observational learning of actions, goals, and
      results in children. Some copying was found for apes as well, but only if their
      performance was averaged across trials.

PMID- 20686813
TI  - Chlamydia trachomatis heat shock proteins 60 and 10 induce apoptosis in
      endocervical epithelial cells.
AB  - AIM AND OBJECTIVE: The potential role of chlamydial heat shock proteins (cHSP) 60
      and cHSP10 in apoptosis of primary cervical epithelial cells was investigated.
      METHODS: Primary cervical epithelial cells were stimulated with cHSP60 and cHSP10
      for 4 h. Quantitative measurements of apoptosis were made using cytofluorometry,
      and apoptosis-related genes were analyzed by microarray, real-time PCR and
      western blotting. Further, levels of proinflammatory cytokines (IL-18 and IL
      1beta) were determined by semi-quantitative RT-PCR. RESULTS: After a 4-h
      incubation in the presence of recombinant cHSP60 or cHSP10, the number of cells
      exhibiting annexin V binding activity increased 6- and 5-fold, respectively (P <
      0.05). A DNA microarray study showed significant (P < 0.05) upregulation of
      interleukin (IL)-1 beta-convertase, and caspase-3, -8 and -9 genes in cHSP60- and
      cHSP10-stimulated than in control cells as confirmed by real-time RT-PCR and
      western blotting. Transcript levels of IL-1beta and IL-18 in cells treated with
      cHSP60 and cHSP10 were found to be significantly (P < 0.05) higher in stimulated
      than in control cells. CONCLUSION: cHSP60- and cHSP10-induced caspase expression,
      proinflammatory cytokine production and apoptosis of primary cervical epithelial
      cells might play a role in the pathogenesis of infertility in women with
      persistent chlamydial infection.

PMID- 20686815
TI  - The cold European winter of 2005-2006 assisted the spread and persistence of H5N1
      influenza virus in wild birds.
AB  - In January 2006, a major cold spell affected Europe, coinciding with an increase
      of H5N1 influenza virus detected in wild birds, mostly dead mute swans, starting
      along the River Danube and the Mediterranean coast line. Subsequently H5N1
      detections in wild birds were concentrated in central and western parts of
      Europe, reaching a peak in mid February. We tested the hypothesis that the
      geographic distribution of these H5N1 infections was modulated by the long-term
      wintering line, the 0  degrees C isotherm marking the limit beyond which areas
      are largely unsuitable for wintering waterfowl. Given the particularly cold 2005
      2006 European winter, we also considered the satellite-derived contemporary frost
      conditions. This brought us to select the long-term maximum rather than the mean
      January 0  degrees C isotherm as the best approximation for the 2005-2006
      wintering line. Our analysis shows that H5N1 detection sites were closer to the
      wintering line than would be expected by chance, even when the geographic
      distribution of water bird wintering sites was accounted for. We argue that
      partial frost conditions in water bodies are conducive to bird congregation, and
      this may have enhanced H5N1 transmission and local spread. Because the
      environmental virus load also would build up in these hot spots, H5N1 virus may
      have readily persisted during the spring, at least in cooler areas. We conclude
      that H5N1 introduction, spread, and persistence in Europe may have been enhanced
      by the cold 2005-2006 winter.

PMID- 20686816
TI  - Nutlin-1 strengthened anti-proliferation and differentiation-inducing activity of
      ATRA in ATRA-treated p-glycoprotein deregulated human myelocytic leukemia cells.
AB  - Unlike its cytotoxicity in p53-functional cell lines, Nutlin-1, the small
      molecule inhibitor of murine double minute (MDM2), significantly enhanced the
      differentiation-inducing activity of all-trans retinoic acid (ATRA) in HL60 and
      NB4 cells (p53-nonfunctional) but not in U937 cells (p53 wild-type). Moreover, we
      demonstrated that the synergistic differentiation-inducing activity of Nutlin-1
      combined with ATRA appeared in a p53-independent manner. In the present study, we
      found that ATRA could selectively induce expression of p-glycoprotein (p-gp) in
      HL60 and NB4 cells but not in U937 cells. Investigation of p-gp-ATPase activity
      showed that Nutlin-1 and ATRA were likely to act as p-gp transport substrates.
      Furthermore, Nutlin-1 enhanced the ability of ATRA to induce expression of the
      myeloid differentiation-related transcription factor C/EBPbeta and to reduce
      expression of c-myc. Additionally, the expression of retinoic acid receptor alpha
      (RARalpha) was further reduced in cells treated with ATRA in combination with
      Nutlin-1. Taken together, the mechanisms of synergistic differentiation-inducing
      activity of Nutlin-1 combined with ATRA could be attributed to Nutlin-1
      competitive binding to p-gp, leading to ATRA efflux inhibition, and then the
      differentiation pathways involved were therefore further activated. Nutlin-1
      might be a useful adjuvant with ATRA for patients with retinoid-resistant
      leukemia induced by overexpression of p-gp.

PMID- 20686817
TI  - Phase I study of vorinostat (suberoylanilide hydroxamic acid, NSC 701852) in
      combination with docetaxel in patients with advanced and relapsed solid
      malignancies.
AB  - INTRODUCTION: Vorinostat is an inhibitor of histone deacetylase 6, which
      acetylates tubulin and stabilizes microtubules. Since taxanes also stabilize
      microtubules, we hypothesized that the administration of vorinostat followed by
      docetaxel should result in synergistic cytotoxicity. We conducted a phase I trial
      to determine the dose level of vorinostat plus docetaxel that would result in
      dose-limiting toxicity (DLT) in <=30% of patients. METHODS: Eligible patients had
      castration-resistant prostate cancer (CRPC) or relapsed urothelial or non-small
      cell lung cancer (NSCLC) after >=1 prior chemotherapy regimen not containing
      docetaxel, performance status of 0-2, and adequate organ function. Vorinostat was
      given orally for 14 days beginning on day 1 of a 21-day cycle, with docetaxel
      given intravenously over 1 h on day 4. The time-to-event continuous reassessment
      method (TITE-CRM) guided dose escalation. Dose levels (DL) -1, 0, 1 and 2
      corresponded to vorinostat 100, 100, 200 and 200 mg plus docetaxel 50, 60, 60,
      and 75 mg/m(2), respectively. Pharmacokinetic studies were performed on days 1
      and 4 of cycle 1. RESULTS: Twelve patients were enrolled: median age 65 years
      (range 49-74); 9 male, 3 female; 4 CRPC, 5 urothelial, 3 NSCLC. The median number
      of cycles administered was 2. Two patients were treated at DL -1, 4 at DL 0, 5 at
      DL 1 and 1 at DL 2. Five DLTs occurred in 5 patients: neutropenic fever/sepsis
      (2), anaphylactic reaction (1), myocardial infarction (1) and gastrointestinal
      bleed (1). Other toxicities included grade 3/4 neutropenia (4), peripheral
      neuropathy (1), and gastrointestinal bleed (n = 1). The estimated probability of
      DLT for DL -1 was 0.32 (90% posterior probability interval [PI], 0.11 to 0.53)
      for DL 0, 0.38 (90% PI, 0.16 to 0.58) and for DL 1, 0.43 (90% PI, 0.23 to 0.64).
      The trial was stopped due to excessive toxicity. No responses were noted.
      CONCLUSIONS: The combination of vorinostat and docetaxel was poorly tolerated
      with excessive DLTs that required early study termination. No responses were
      identified. Vorinostat and docetaxel pharmacokinetics were comparable to previous
      reports in the literature, without obvious drug-drug interactions.

PMID- 20686818
TI  - Protoapigenone, a natural derivative of apigenin, induces mitogen-activated
      protein kinase-dependent apoptosis in human breast cancer cells associated with
      induction of oxidative stress and inhibition of glutathione S-transferase pi.
AB  - Protoapigenone, a natural derivative of the flavonoid apigenin, has been shown to
      exhibit potent antitumor activity in vitro and in vivo; the precise mechanism of
      action, however, is not fully elucidated. In this study, we investigated and
      compared the mechanisms by which protoapigenone and apigenin caused cell death in
      the human breast cancer MDA-MB-231 cells. Flow cytometry analysis revealed that
      protoapigenone induced apoptosis with 10-fold greater potency than apigenin.
      Cancer cells treated with protoapigenone resulted in persistent activation of
      mitogen-activated protein kinase (MAPK) ERK, JNK, and p38, hyperphosphorylation
      of Bcl-2 and Bcl-xL, and loss of mitochondrial membrane potential (MMP). The MAPK
      inhibitors effectively prevented the loss of MMP and apoptosis induced by
      protoapigenone. Treatment of cells with protoapigenone led to increased levels of
      reactive oxygen species (ROS) and decreased levels of intracellular glutathione.
      The thiol-antioxidant N-acetylcysteine abolished protoapigenone-induced MAPK
      activation, mitochondrial dysfunction, and apoptosis. These results suggest that
      the induction of oxidative stress preceding the activation of MAPK is required to
      initiate the mitochondria-mediated apoptosis induced by protoapigenone.
      Additionally, protoapigenone-induced JNK activation was linked to thiol
      modification of glutathione S-transferase pi (GSTpi), which impeded GSTpi
      inhibition of JNK. In contrast to protoapigenone, apigenin-induced apoptosis was
      neither dependent on ROS nor on MAPK. Structure-activity relationship studies
      suggested that the thiol reacting effect of protoapigenone might be associated
      with an alpha, beta-unsaturated ketone moiety in the structure of ring B.

PMID- 20686819
TI  - Different sized somatic NF1 locus rearrangements in neurofibromatosis 1
      associated malignant peripheral nerve sheath tumors.
AB  - Neurofibromatosis type 1 (NF1) patients are at increased risk of developing both
      benign (neurofibromas) and malignant (malignant peripheral nerve sheath tumors,
      MPNST) tumors. Molecular data on tumor progression are scarce, and few studies
      have compared the NF1 locus copy number in these two tumor types. To further
      explore the role of such NF1 locus rearrangements in NF1 tumorigenesis, and the
      likely disruption to the associated genes, the NF1 gene region was analyzed in
      NF1-associated tumors. DNA from three MPNSTs and one neurofibroma, excised from
      three unrelated NF1 patients, were analyzed using an NF1 region customized array
      based comparative genomic hybridization. The somatic NF1 inactivation mutational
      mechanisms associated with MPNSTs appear to be different from those in benign
      neurofibromas. Interestingly, the MPNST-associated deletion breakpoints did not
      involve the paralogous repetitive sequences that are involved in most germline
      NF1 deletions. The somatic smallest common region of deletion overlap, however,
      was restricted to approximately the same ~2.2-Mb interval that encompassed most
      of the genes deleted in NF1 recurrent constitutional deletions. A number of genes
      in addition to NF1 on 17q (centromere to 17q24.2) may be involved in MPNST
      development. A larger study is warranted to confirm these findings. As NF1
      patients with such germline NF1 deletions do exhibit increased risk of developing
      MPNST, these present findings emphasize the likely role of at least some of these
      NF1 flanking genes in MPNST pathobiology.

PMID- 20686820
TI  - Correlation between O6-methylguanine-DNA methyltransferase and survival in
      elderly patients with glioblastoma treated with radiotherapy plus concomitant and
      adjuvant temozolomide.
AB  - Epigenetic silencing of the O(6)-methylguanine-DNA-methyltransferase (MGMT) gene
      by promoter methylation is correlated with improved progression-free survival
      (PFS) and overall survival (OS) in adult patients with newly diagnosed
      glioblastoma multiforme (GBM) who receive alkylating agents. The aim of this
      study is to determine the correlation between MGMT and survival in elderly
      patients with GBM treated with radiotherapy (RT) and temozolomide (TMZ). Eighty
      three patients aged 70 years or older with histologically confirmed GBM treated
      with RT plus TMZ between February 2005 and September 2009 were investigated in
      this study. The methylation status of the MGMT promoter was determined by
      polymerase chain reaction analysis. Median PFS and OS were 7.5 and 12.8 months,
      respectively. The MGMT promoter was methylated in 42 patients (50.6%) and
      unmethylated in 41 patients (49.4%). Median OS was 15.3 months in methylated
      patients and 10.2 months in unmethylated patients (P = 0.0001). Median PFS was
      10.5 months in methylated tumors and 5.5 months in unmethylated tumors (P =
      0.0001). On multivariate analysis MGMT methylation status emerged as the
      strongest independent prognostic factor for OS and PFS (P = 0.004 and P = 0.005,
      respectively). The results of the present study suggest that MGMT methylation
      status might be an important prognostic factor associated with better OS and PFS
      in elderly patients with GBM treated with RT and TMZ.

PMID- 20686822
TI  - Venous thromboembolism (VTE) in hospitalized cancer patients: prophylaxis failure
      or failure to prophylax!
AB  - Cancer patients are at higher risk for venous thromboembolism (VTE).
      Anticoagulants, when used for prophylaxis, had successfully reduced the incidence
      of VTE in high risk patients. Nevertheless, many registry studies have shown low
      compliance rate with published prophylaxis guidelines. From January 2004 through
      June 2008, hospital database was searched for all discharge diagnoses of cancer
      with deep vein thrombosis (DVT) and/or pulmonary embolism (PE). Prophylaxis rate
      for the whole group and for subgroups in relation to recent hospitalization,
      duration of cancer diagnosis and number of other coexisting risk factors were
      studied. Two hundred patients were identified; majority (91.8%) had advanced
      stage cancer at time of VTE diagnosis. In addition to cancer, many patients had
      multiple coexisting risk factors for VTE with 137 (68.5%) patients had at least
      three while 71 (35.5%) had four or more. Overall, 111(55.5%) patients developed
      lower-extremity DVT while 52 (26%) patients developed PE, other sites accounted
      for 18%. Majority of the patients (72%) had VTE diagnosed within the first 12
      months following cancer diagnosis. Almost three quarters of the patients (73.5%)
      had not received any antecedent prophylaxis. Prophylaxis rate was 23% among
      patients with >= 3 risk factors and 50% among the highest risk group with >= 5
      risk factors. Based on our findings, majority of VTE in cancer patients occurred
      due to failure to offer prophylaxis, minority were due to prophylaxis failure.
      Meticulous quality improvement programs should be established to emphasize the
      importance of implementing more intensive prophylaxis among high-risk cancer
      patients.

PMID- 20686821
TI  - Growth curve analysis of asymptomatic and symptomatic meningiomas.
AB  - Meningiomas sometimes appear to stop growing after attaining a large size.
      Commonly used exponential growth models do not reflect this phenomenon. We
      attempted to find the best curve to simulate their growth. Fifty-two patients
      with meningioma were followed up for 3.1-21.7 years (mean 7.5 years) with four or
      more imaging studies each. Thirty-one patients had asymptomatic tumors. The other
      21 patients with residual or recurrent tumor were followed up after surgery. Time
      volume curves for each tumor were plotted. Nonlinear regression analyses were
      performed against power, exponential, logistic, and Gompertzian curves. Time
      volume curves corresponded to the Gompertzian and logistic growth curves better
      than to power or exponential curves. When simulating time-volume curves with
      Gompertzian curves, the majority of benign meningiomas began to slow their growth
      before patient age of 80 years. Twenty-three of 31 asymptomatic meningiomas had
      already passed the inflection point before diagnosis. In contrast, this happened
      less frequently in symptomatic tumors. Especially, all six atypical meningiomas
      continued to grow quasi-exponentially. Sigmoid curves that approach a plateau
      were better descriptors of the growth of benign meningiomas than were curves of
      unlimited growth. However, atypical meningiomas were unlikely to slow their
      growth.

PMID- 20686823
TI  - The eighth American college of chest physicians guidelines on venous
      thromboembolism prevention: implications for hospital prophylaxis strategies.
AB  - Venous thromboembolism (VTE) is the most common potentially preventable form of
      hospital-related mortality. It presents as a major healthcare burden, affecting
      both medical and surgical patients. The prevention of VTE has been identified as
      one of the most important in-hospital safety practices in the US. VTE guideline
      recommendations provide a framework for clinical practice and guide VTE
      prophylaxis policies. Guidelines produced by the American College of Chest
      Physicians (ACCP) are considered to be the 'gold standard' in VTE prevention,
      diagnosis and management, and have been updated. A number of differences exist
      between the new 2008 ACCP guidelines on VTE prevention and the previous version
      published in 2004. There are variations regarding VTE prevention, including new
      and stronger evidence-based recommendations for several indications and agents.
      The updated guidelines give a strong recommendation that every hospital develop a
      VTE prevention policy, which is particularly important given the current
      international drive to reduce the incidence of VTE. A formal hospital policy
      should help improve compliance with appropriate VTE prophylaxis strategies. The
      ACCP guidelines form a basis for improving patient safety at a time of public
      reporting of quality of care, hospital accreditation, national standards of care,
      and pay for performance initiatives. In this review, changes in recommendations
      for VTE prevention in the 2008 ACCP guidelines compared with the previous edition
      in 2004 are outlined. In addition, outstanding areas of debate are discussed and
      the role of the 2008 ACCP guidelines in the context of the new VTE performance
      measures analyzed.

PMID- 20686824
TI  - Isolation and characterization of an Arthrobacter sp. strain HB-5 that transforms
      atrazine.
AB  - A bacterial strain (HB-5) capable of utilizing atrazine as sole carbon and
      nitrogen source for growth was isolated from an industrial wastewater sample by
      enrichment culture. The isolate was identified as Arthrobacter sp. according to
      its phenotypic features, physiologic and biochemical characteristics, and
      phylogenetic analysis. The strain exhibited faster atrazine degradation rates in
      atrazine-containing mineral media than the well-characterized atrazine-degrading
      bacteria Pseudomonas sp. ADP. The broad optimum pH and temperature ranges
      observed for strain HB-5 indicate that it has potential for remediation of
      atrazine-contaminated sites. Strain HB-5 first metabolizes atrazine to yield
      hydroxyatrazine. Then, the bacterium metabolizes hydroxyatrazine to cyanuric
      acid, but could not mineralize atrazine.

PMID- 20686825
TI  - Preparation and characterization of hybrid pH-sensitive hydrogels of chitosan-co
      acrylic acid for controlled release of verapamil.
AB  - In the present work crosslinked hydrogels based on chitosan (CS) and acrylic acid
      (AA) were prepared by free radical polymerization with various feed compositions
      using N,N methylenebisacrylamide (MBA) as crosslinking agent. Benzoyl peroxide
      was used as catalyst. Fourier transform infrared spectra (FTIR) confirmed the
      formation of the crosslinked hydrogels. This hydrogel is formed due to
      electrostatic interaction between cationic groups in CS and anionic groups in AA.
      Prepared hydrogels were used for dynamic and equilibrium swelling studies. For
      swelling behavior, effect of pH, polymeric and monomeric compositions and degree
      of crosslinking were investigated. Swelling studies were performed in USP
      phosphate buffer solutions of varying pH 1.2, 5.5, 6.5 and 7.5. Results showed
      that swelling increased by increasing AA contents in structure of hydrogels in
      solutions of higher pH values. This is due to the presence of more carboxylic
      groups available for ionization. On the other hand by increasing the chitosan
      content swelling increased in a solution of acidic pH, but this swelling was not
      significant and it is due to ionization of amine groups present in the structure
      of hydrogel. Swelling decreased with increase in crosslinking ratio owing to
      tighter hydrogel structure. Porosity and sol-gel fraction were also measured.
      With increase in CS and AA contents porosity and gel fraction increased, whereas
      by increasing MBA content porosity decreased and gel fraction increased.
      Furthermore, diffusion coefficient (D) and the network parameters i.e., the
      average molecular weight between crosslinks (M(c)), polymer volume fraction in
      swollen state (V(2s)), number of repeating units between crosslinks (M(r)) and
      crosslinking density (q) were calculated using Flory-Rehner theory. Selected
      samples were loaded with a model drug verapamil. Release of verapamil depends on
      the ratios of CS/AA, degree of crosslinking and pH of the medium. The release
      mechanisms were studied by fitting experimental data to model equations and
      calculating the corresponding parameters. The result showed that the kinetics of
      drug release from the hydrogels in both pH 1.2 and 7.5 buffer solutions was
      mainly non-Fickian diffusion.

PMID- 20686826
TI  - Intestinal absorption of HMG-CoA reductase inhibitor pravastatin mediated by
      organic anion transporting polypeptide.
AB  - PURPOSE: The purpose of this study is to clarify the impact of organic anion
      transporting polypeptide (Oatp) on intestinal absorption of the HMG-CoA reductase
      inhibitor, pravastatin. METHODS: OATP/Oatp-mediated pravastatin uptake was
      evaluated with Xenopus oocytes systems. Intestinal permeability was measured by
      an in situ closed loop method in rats. In vivo pravastatin absorption was
      kinetically assessed by measuring plasma concentration after oral administration
      in rats. RESULTS: Uptake of pravastatin by Oatp1a5, Oatp2b1, OATP1A2, and OATP2B1
      cRNA-injected Xenopus oocytes was significantly increased compared with that by
      water-injected oocytes. Naringin, a potent inhibitor of Oatps and Mdr1, decreased
      the Oatp1a5-mediated uptake of pravastatin with IC (50) value of 30.4 MUM. Rat
      intestinal permeability of pravastatin was significantly reduced in the presence
      of 1,000 MUM naringin. Similar results were obtained in in vivo absorption
      studies in rats. Furthermore, no significant change in the permeability was
      observed in the presence of elacridar, a potent inhibitor of both Mdr1 and Bcrp,
      though the permeability was significantly decreased in the presence of both
      elacridar and naringin, suggesting that Mdr1 and Bcrp are not involved in
      intestinal absorption of pravastatin. CONCLUSION: Oatp, but not by Mdr1 or Bcrp,
      contributes to the intestinal absorption of pravastatin in rats.

PMID- 20686827
TI  - Structures and connections of enkephalin- and gamma-aminobutyric acid
      immunoreactive profiles in the gustatory region of the nucleus tractus
      solitarius: a light and electron microscopic study.
AB  - GABA and enkephalin (ENK) are principle inhibitory transmitters in the rostral
      portion of the nucleus tractus solitarius (rNTS) for regulating the gustatory
      information. Although the existence of GABA- and ENK-immunoreactive (ir) profiles
      in the rNTS has been demonstrated, there are no morphological data revealing the
      connections between them. In the present study, using immunofluorescent and
      electron microscopic methods, we examined their relationship in the rNTS of rat.
      Results showed the following: (1) dense ENK-ir fibers and terminals and GABA-ir
      cell bodies, fibers, and terminals were observed in the rNTS; (2) ENK-ir
      terminals mainly make symmetric synapses with GABA-ir and immunonegative somas
      and dendrites; (3) co-existence of ENK/GABA-ir axon terminals and convergence of
      ENK- and GABA-ir terminals on one immunonegative soma or dendrite can also be
      observed. These results suggest that ENK should inhibit directly or excite
      indirectly (by blocking the inhibition of the GABAergic neurons) the gustatory
      neurons in the rNTS.

PMID- 20686828
TI  - Hyper-production and characterization of the iota-carrageenase useful for iota
      carrageenan oligosaccharide production from a deep-sea bacterium, Microbulbifer
      thermotolerans JAMB-A94T, and insight into the unusual catalytic mechanism.
AB  - A gene of unknown function from the genome of the agar-degrading deep-sea
      bacterium Microbulbifer thermotolerans JAMB-A94(T) was functionally identified as
      a iota-carrageenase gene. This gene, designated as cgiA, is located together with
      two beta-agarase genes, agaA and agaO in a cluster. The cgiA gene product is 569
      amino acids and shares 29% identity over 185 amino acids with the iota
      carrageenase from Zobellia galactanivorans Dsij DSM 12802. Recombinant, cgiA
      encoded iota-carrageenase (55 kDa) was hyper-produced in Bacillus subtilis. The
      recombinant enzyme shows maximal activity at 50 degrees C, the highest reported
      optimal temperature for a carrageenase. It cleaved beta-1,4 linkages in iota
      carrageenan to produce a high ratio of iota-carrageenan tetramer, more than 75%
      of the total product, and did not cleave the beta-1,4 linkages in kappa- or
      lambda-carrageenan. Therefore, this enzyme may be useful for industrial
      production of iota-carrageenan oligosaccharides, which have demonstrated
      antiviral potential against diverse viruses. Furthermore, we performed site
      directed mutagenesis on the gene to identify the catalytic amino acid residues.
      We demonstrated that a conserved Glu351 was essential for catalysis; however,
      this enzyme lacked a catalytic Asp residue, which is generally critical for the
      catalytic activity of most glycoside hydrolases.

PMID- 20686829
TI  - Does dehydroepiandrosterone influence the expression of urticaria?-a mini review.
AB  - Chronic urticaria is a challenging problem since the exact cause and mechanism
      involved in the disease development have still remained unknown. This disease is
      associated with mast cells activation and immunoinflammatory processes.
      Interestingly, dysfunctions of the neuroendocrine-immune system due to stress and
      other factors seem to appear as a very interesting theory for urticaria
      pathogenesis. Dehydroepiandrosterone and its sulfate derivative (DHEA-S) appear
      to have regulatory effects in immune homeostasis and are regulated by the nervous
      system, and it is suggested that they may be an integral element of
      neuroimmunomodulation. Our studies showed substantially decreased serum
      concentration of DHEA-S in patients with chronic urticaria. However, current
      knowledge prevents answering whether lower circulating DHEA-S concentration is a
      primary phenomenon or just an accompanying one which appears as a response of
      different systems to the course of the illness and may not be of any importance
      for the pathogenesis of urticaria whatsoever. This review is a summary of
      clinical research on the role of DHEA in chronic urticaria.

PMID- 20686830
TI  - Kakkalide and its metabolite irisolidone ameliorate carrageenan-induced
      inflammation in mice by inhibiting NF-kappaB pathway.
AB  - The anti-inflammatory activities of kakkalide, a major constituent of the flower
      of Pueraria thunbergiana, and irisolidone, a metabolite of kakkalide produced by
      intestinal microflora, against carrageenan-induced inflammation in air pouches on
      the backs of mice and in lipopolysaccharide (LPS)-stimulated peritoneal
      macrophages were investigated. Kakkalide and irisolidone down-regulated the gene
      expression of cytokines [tumor necrosis factor alpha (TNF-alpha) and interleukin
      1 beta (IL-1beta)] and cyclooxygenase-2 (COX-2) and the production of pro
      inflammatory cytokines, TNF-alpha and IL-1beta, and inflammatory mediators, NO
      and prostaglandin E(2) (PGE(2)), in LPS-stimulated peritoneal macrophages. These
      agents also inhibited the phosphorylation of IkappaB-alpha and the nuclear
      translocation of nuclear factor-kappa B (NF-kappaB). Orally administered
      kakkalide and irisolidone significantly reduced carrageenan-induced inflammatory
      markers, leukocyte number, and protein amount in the exudates of the air pouch.
      These constituents also inhibited PGE(2) production and COX-2 inducible nitric
      oxide synthase, IL-1beta, and TNF-alpha expression. These agents also inhibited
      NF-kappaB activation. The anti-inflammatory effects of irisolidone were more
      potent than those of kakkalide. Based on these findings, kakkalide and
      irisolidone may inhibit inflammatory reactions via NF-kappaB pathway, and
      irisolidone, a metabolite of kakkalide, may more potently inhibit these
      inflammatory reactions.

PMID- 20686831
TI  - IgE, COX-2, and IL-4 are expressed by DEHP through p38 MAPK and suppressed by
      plant glycoprotein (75 kDa) in ICR mice.
AB  - The aim of the present study was to evaluate the inhibitory effect of
      glycoprotein isolated from Cudrania tricuspidata Bureau (CTB glycoprotein) on
      di(2-ethylhexyl) phthalate (DEHP)-induced allergic inflammatory response in mice.
      We evaluated the activity of beta-hexosaminidase, expression of cyclooxygenase
      (COX)-2, p38 mitogen-activated protein kinase (MAPK), and activator protein (AP)
      1, and production of immunoglobulin (Ig)E and interleukin (IL)-4 in DEHP-treated
      RBL-2H3 cells and ICR mice. Our results revealed that the CTB glycoprotein
      inhibited the activity of beta-hexosaminidase and production of IgE and IL-4 in
      serum from DEHP-treated mice. We also found that the CTB glycoprotein reduced
      arachidonic acid release, COX-2 expression, and AP-1 transcriptional activation
      through p38 MAPK phosphorylation in DEHP-treated RBL-2H3 cells. The activation of
      AP-1 was completely blocked by treatment with p38 MAPK inhibitor (SKF86002). The
      results from these experiments indicate that CTB glycoprotein effectively
      protects against the allergic inflammation response, mainly through
      downregulation of MAPK/AP-1 in the mast cell degranulation stage. In conclusion,
      we suggest that the CTB glycoprotein may be one component of health supplements
      for the prevention of allergic inflammation.

PMID- 20686832
TI  - Information transfer during a transitive reasoning task.
AB  - For about two decades now, the localization of the brain regions involved in
      reasoning processes is being investigated through fMRI studies, and it is known
      that for a transitive form of reasoning the frontal and parietal regions are most
      active. In contrast, less is known about the information exchange during the
      performance of such complex tasks. In this study, the propagation of brain
      activity during a transitive reasoning task was investigated and compared to the
      propagation during a simple memory task. We studied EEG transmission patterns
      obtained for physiological indicators of brain activity and determined whether
      there are frequency bands specifically related to this type of cognitive
      operations. The analysis was performed by means of the directed transfer
      function. The transmission patterns were determined in the theta, alpha and gamma
      bands. The results show stronger transmissions in theta and alpha bands from
      frontal to parietal as well as within frontal regions in reasoning trials
      comparing to memory trials. The increase in theta and alpha transmissions was
      accompanied by flows in gamma band from right posterior to left posterior and
      anterior sites. These results are consistent with previous neuroimaging (fMRI)
      data concerning fronto-parietal regions involvement in reasoning and working
      memory processes and also provide new evidence for the executive role of frontal
      theta waves in organizing the cognition.

PMID- 20686833
TI  - Bone mineral density loss during adjuvant chemotherapy in pre-menopausal women
      with early breast cancer: is it dependent on oestrogen deficiency?
AB  - Pre-menopausal women given adjuvant chemotherapy for breast cancer experience
      both premature ovarian failure and loss of bone mineral density (BMD), and this
      study was designed to see if these observations are causally linked. Chemotherapy
      was administered to 41 pre-menopausal women with early breast cancer enrolled
      prospectively in a study of ovarian function and BMD in such women given systemic
      therapy. After giving written informed consent, all patients underwent baseline
      and regular on-treatment measurements of BMD by dual-energy X-ray absorptiometry
      (DXA) scan, bone turnover and ovarian function by analysis of serum hormone
      levels and self-reported menstrual diaries. Baseline lumbar spine BMD in the 41
      women given chemotherapy was higher than the normal population (Z score 0.28 +/-
      0.14 (mean +/- SEM), P = 0.047), and fell significantly over the first 6 months
      from a mean of 1.05-1.01 g/m(2), P < 0.0001, and similar but smaller changes were
      demonstrated in hip BMD. This fall was independent of age at diagnosis, type of
      chemotherapy, development of amenorrhoea or either baseline or on-treatment
      estradiol concentration. During the 6 months after completion of adjuvant
      chemotherapy, BMD fell further only in those women with low estradiol or
      experiencing amenorrhoea during the first 6 months, although all groups showed
      evidence of increased bone turnover. This study demonstrates loss of both spine
      and hip BMD in pre-menopausal women during 6 months' adjuvant systemic
      chemotherapy to be independent of changes in ovarian function. Ovarian function
      was, however, related to BMD changes after chemotherapy ceased.

PMID- 20686834
TI  - Does race modify the association between CYP1B1 Val432Leu polymorphism and breast
      cancer risk? A critical appraisal of a recent meta-analysis.

PMID- 20686835
TI  - Combined UGT1A1 and UGT1A6 genotypes together with a stressful life event
      increase breast cancer risk.

PMID- 20686836
TI  - Effects of breast cancer surgery and surgical side effects on body image over
      time.
AB  - We examined the impact of surgical treatments (breast-conserving surgery [BCS],
      mastectomy alone, mastectomy with reconstruction) and surgical side-effects
      severity on early stage (0-IIA) breast cancer patients' body image over time. We
      interviewed patients at 4-6 weeks (T1), six (T2), 12 (T3), and 24 months (T4)
      following definitive surgical treatment. We examined longitudinal relationships
      among body image problems, surgery type, and surgical side-effects severity using
      the Generalized Estimating Equation approach, controlling for demographic,
      clinical, and psychosocial factors. We compared regression coefficients of
      surgery type from two models, one with and one without surgical side-effects
      severity. Of 549 patients enrolled (mean age 58; 75% White; 65% BCS, 12%
      mastectomy, 23% mastectomy with reconstruction), 514 (94%) completed all four
      interviews. In the model without surgical side-effects severity, patients who
      underwent mastectomy with reconstruction reported poorer body image than patients
      who underwent BCS at T1-T3 (each P < 0.02), but not at T4. At T2, patients who
      underwent mastectomy with reconstruction also reported poorer body image than
      patients who underwent mastectomy alone (P = 0.0106). Adjusting for surgical side
      effects severity, body image scores did not differ significantly between patients
      with BCS and mastectomy with reconstruction at any interview; however, patients
      who underwent mastectomy alone had better body image at T2 than patients who
      underwent mastectomy with reconstruction (P = 0.011). The impact of surgery type
      on body image within the first year of definitive surgical treatment was
      explained by surgical side-effects severity. After 2 years, body image problems
      did not differ significantly by surgery type.

PMID- 20686837
TI  - Rapamycin synergizes cisplatin sensitivity in basal-like breast cancer cells
      through up-regulation of p73.
AB  - Recent gene expression profiling studies have identified five breast cancer
      subtypes, of which the basal-like subtype is the most aggressive. Basal-like
      breast cancer poses serious clinical challenges as there are currently no
      targeted therapies available to treat it. Although there is increasing evidence
      that these tumors possess specific sensitivity to cisplatin, its success is often
      compromised due to its dose-limiting nephrotoxicity and the development of drug
      resistance. To overcome this limitation, our goal was to maximize the benefits
      associated with cisplatin therapy through drug combination strategies. Using a
      validated kinase inhibitor library, we showed that inhibition of the mTOR,
      TGFbetaRI, NFkappaB, PI3K/AKT, and MAPK pathways sensitized basal-like MDA-MB-468
      cells to cisplatin treatment. Further analysis demonstrated that the combination
      of the mTOR inhibitor rapamycin and cisplatin generated significant drug
      synergism in basal-like MDA-MB-468, MDA-MB-231, and HCC1937 cells but not in
      luminal-like T47D or MCF-7 cells. We further showed that the synergistic effect
      of rapamycin plus cisplatin on basal-like breast cancer cells was mediated
      through the induction of p73. Depletion of endogenous p73 in basal-like cells
      abolished these synergistic effects. In conclusion, combination therapy with mTOR
      inhibitors and cisplatin may be a useful therapeutic strategy in the treatment of
      basal-like breast cancers.

PMID- 20686838
TI  - Use of three bivalve species for biomonitoring a polluted estuarine environment.
AB  - Estuaries are marine areas at great contamination risk due to their hydrodynamic
      features. PAH are wide and ubiquitous contaminants with a high presence in these
      marine environments. Chemical analysis of sediments can provide information,
      although it does not give a direct measure of the toxicological effect of such
      contaminants in the biota. Samples of Venerupis pullastra, Cerastoderma edule,
      and Mytilus galloprovincialis were collected from two locations in Corcubion
      estuary (Norhwest of Spain). The level of PAH in sediment and biota, and its
      possible origin were assessed. A moderate level of contamination was observed
      with a predominance of PAH of a pyrogenic origin. Genotoxic damage, measured as
      single-strand DNA breaks with the comet assay, was evaluated in gill tissue and
      in hemolymph. The values of DNA damage obtained showed a higher sensitivity of
      clams and cockles to the pollution load level. These differences among species
      make us suggest the use of some other species coupled with mussels as an optimal
      tool for biomonitoring estuarine environments.

PMID- 20686839
TI  - Impact of anthropogenic input on physicochemical parameters and trace metals in
      marine surface sediments of Bay of Bengal off Chennai, India.
AB  - The study of heavy metal distribution in coastal surface sediments is an
      important component in understanding the exogenic cycling as well as in assessing
      the effect of anthropogenic influences on the marine ecosystem. In this study,
      surface sediment samples were collected from five different traverses along the
      innershelf of Bay of Bengal, off Chennai, India during pre- and post-monsoon
      seasons. The results of Spearmen correlation matrix, factor and cluster analysis,
      enrichment and contamination factor analysis, and geoaccumulation index of the
      heavy metals analyzed in the collected surface sediment were discussed. The level
      of both enrichment and contamination factor are shown in following order Cd > Cu
      > Cr > Ni > Pb > Co > Zn > Mn > Fe > Hg. The geoaccumulation index suggests that
      Cd and Cu are strongly to extremely pollute the sediments in both seasons. The
      results strongly indict anthropogenic sources for moderate input of Cd and Cu in
      to the innershelf of Chennai coast.

PMID- 20686840
TI  - Indicator and probability kriging methods for delineating Cu, Fe, and Mn
      contamination in groundwater of Najafgarh Block, Delhi, India.
AB  - Two non-parametric kriging methods such as indicator kriging and probability
      kriging were compared and used to estimate the probability of concentrations of
      Cu, Fe, and Mn higher than a threshold value in groundwater. In indicator
      kriging, experimental semivariogram values were fitted well in spherical model
      for Fe and Mn. Exponential model was found to be best for all the metals in
      probability kriging and for Cu in indicator kriging. The probability maps of all
      the metals exhibited an increasing risk of pollution over the entire study area.
      Probability kriging estimator incorporates the information about order relations
      which the indicator kriging does not, has improved the accuracy of estimating the
      probability of metal concentrations in groundwater being higher than a threshold
      value. Evaluation of these two spatial interpolation methods through mean error
      (ME), mean square error (MSE), kriged reduced mean error (KRME), and kriged
      reduced mean square error (KRMSE) showed 3.52% better performance of probability
      kriging over indicator kriging. The combined result of these two kriging method
      indicated that on an average 26.34%, 65.36%, and 99.55% area for Cu, Fe, and Mn,
      respectively, are coming under the risk zone with probability of exceedance from
      a cutoff value is 0.6 or more. The groundwater quality map pictorially represents
      groundwater zones as "desirable" or "undesirable" for drinking. Thus the
      geostatistical approach is very much helpful for the planners and decision makers
      to devise policy guidelines for efficient management of the groundwater resources
      so as to enhance groundwater recharge and minimize the pollution level.

PMID- 20686841
TI  - Heart failure is an especially important problem in the elderly.

PMID- 20686843
TI  - The effect of kidney diseases on survival in liver transplant patients.
AB  - BACKGROUND: Liver transplantation (LTx) is a life-saving procedure for patients
      with chronic end-stage liver disease or acute liver failure. It is well known
      that kidney diseases such as acute kidney injury (AKI) and chronic kidney disease
      (CKD) are highly prevalent in LTx patients. We aimed to assess the effect of
      kidney disease on survival in LTx patients. MATERIALS AND METHODS: In this study,
      we included 85 patients (mean age 43.7 +/- 12.7, male/female 53/32) who underwent
      orthotopic liver transplantation between 2001 and 2009 and analyzed their medical
      records and laboratory results. The effect of renal dysfunction including CKD and
      AKI on survival in LTx patients was assessed by Kaplan-Meier survival analysis.
      RESULTS: Median duration of follow-up was 48.4 months (2.6-163 months). Before
      transplantation, eleven patients (12.9%) were diagnosed with CKD and nine (10.5%)
      with AKI. AKI developed in 17 patients (20%) in the early post-operative phase,
      among which five had pretransplant CKD. We found that the number of male patients
      and the number of red blood cell transfusions were statistically higher in LTx
      patients with AKI than in those without AKI (p < 0.05). Eight patients died in
      the follow-up period. Estimated survival rates of patients were 93.9, 92.7 and
      90.8% at 1st, 3rd and 5th years, respectively. The survival rate of patients with
      pre-LTx CKD was worse than that of patients with normal kidney function (70.7 vs.
      95.8% in the 3rd year, p = 0.043). We also found that the survival rate of
      patients with post-LTx AKI was lower than in patients with normal kidney function
      (66.7 vs. 96.6% in the 5th year, p < 0.001). CONCLUSION: Our results suggest that
      post-LTx AKI determined by age and pre-LTx CKD had a negative effect on survival
      of LTx patients. These patients should be followed up and carefully managed in
      the perioperative period with the aim of minimizing the kidney dysfunction.

PMID- 20686844
TI  - Drug-induced acute pancreatitis: underdiagnosis and overdiagnosis.

PMID- 20686845
TI  - Sucrose co-administration reduces the toxic effect of lectin on gut permeability
      and intestinal bacterial colonization.
AB  - INTRODUCTION: Legume lectins can have toxic effects when consumed without
      adequate cooking, occasionally leading to an acute gastroenteritis. Lectins are
      sugar binging proteins and may use this property to execute their toxic effects;
      these toxic effects may be secondary to increased gut bacteria and intestinal
      permeability. However, whether or not sucrose rescues these toxic effects by
      decreasing gut bacterial concentration and intestinal permeability is unknown.
      AIM: Our aim was to test the hypothesis that sucrose may reduce toxic effects of
      legume lectins by protecting barrier function, bacterial overgrowth and bacterial
      translocation. METHODS: Twenty-four rats were randomized to an ad libitum diet of
      either standard rat chow, a chow containing 26% crude red kidney beans or a chow
      containing 26% crude red kidney beans supplemented with 1 mM sucrose in drinking
      water for 24 h. After 12-h fast, rats were gavaged with sugar probes; breath gas
      and urine were collected for 5 h. Intestine and liver tissues were then
      collected. Mucosa-associated total bacterial count were measured by targeting the
      16s rRNA gene. Four groups of in vitro Caco-2 cell lines were treated with PBS,
      200 MUg/ml phytohemagglutinin (PHA), 1 mM sucrose and both 200 MUg/ml PHA and 1
      mM sucrose, respectively, and trans-epithelial resistance was measured. RESULTS:
      Rats fed crude red kidney beans for 24 h showed significant weight loss when
      compared to controls (P < 0.05), as well as increased intestinal permeability (P
      < 0.05), increased bacterial load (P < 0.05) and increased bacterial
      translocation to the liver (P < 0.05). Sucrose rescues the drop in trans
      epithelial resistance due to PHA in CaCO2-cells (P < 0.05). CONCLUSIONS: Sucrose
      reduced crude red kidney beans induced increase in intestinal permeability,
      bacterial load and translocation. Since red kidney beans are an important source
      of dietary protein in the world, their potential toxicity when inadequately
      cooked may be rescued by a suitable complementary diet.

PMID- 20686846
TI  - Functional consequence of the STK11 exon 7 duplication mutation identified in a
      Korean child with Peutz-Jeghers syndrome.

PMID- 20686847
TI  - Over-expression of Ephb4 is associated with carcinogenesis of gastric cancer.
AB  - BACKGROUND: Gastric cancer is one of the most frequently diagnosed malignancies
      in the world. The gene expression profile and molecular grouping of gastric
      cancer has been a challenging task due to its inherent complexity and variation
      among individuals. AIMS: To determine the molecular mechanism associated with
      gastric carcinogenesis. METHODS: We analyzed the gene expression profiles of 20
      cancerous tissues and their tumor-adjacent tissue from patients with gastric
      cancer by using a 14 K cDNA microarray. The differentially expressed genes and
      their products were verified by semiquantitative reverse transcription PCR (RT
      PCR), western blotting and immunohistochemistry of gastric cancer and normal
      tissue samples. RESULTS: A total of 69 genes were found to be differentially
      regulated in the cancerous tissue. Among them, genes such as CDH17, ETV4, S100A6,
      S100A11, Ephb4, and KLK10 were confirmed by RT-PCR to be up-regulated, while
      genes such as NK4 and PPP2R1B were down-regulated. Western blotting and
      immunohistochemistry indicated that Ephb4 was over-expressed and localized to the
      cytoplasm of gastric cancer cells. Moreover, Ephb4 protein was observed as being
      significantly related to tumor size and pN category (p = 0.001 and 0.007,
      respectively). CONCLUSIONS: These newly identified genes might provide a valuable
      resource for understanding the molecular mechanism associated with the
      carcinogenesis of gastric cancer and for finding potential diagnostic markers of
      gastric cancer.

PMID- 20686848
TI  - Acute renal failure when exenatide is co-administered with diuretics and
      angiotensin II blockers.
AB  - Case (description) the patient is a 20 years old male smoker, who was diagnosed
      with type 2 diabetes mellitus in 2006. Due to the inadequate response to the
      previously established treatment, the pharmacotherapy was modified by introducing
      exenatide (up to 10 MUg, twice daily) instead of insulin glargine, but
      maintaining the treatment with the diuretic and angiotensin II receptor
      antagonist drugs. Two months later, the patient exhibited a very important
      intolerance to exenatide (continuous nausea, vomiting, and dehydration), finally
      leading to ischemic acute renal failure. When the angiotensin II receptor
      antagonist and exenatide were suspended, a very rapid recovery of renal function
      was observed. Conclusion ischemic acute renal failure is supposed to be the
      consequence of the extracellular volume contraction caused by exenatide (the
      result of continuous nausea and vomiting). This adverse effect could be caused by
      the co-administration of diuretics and angiotensin II receptor antagonists.

PMID- 20686849
TI  - Investigating health and diabetes perceptions among Hmong American children, 9-18
      years of age.
AB  - After immigrating to the United States (US), obesity and diabetes have increased
      among the Hmong. Therefore, this study investigated how Hmong children perceive
      health and diabetes risk so that appropriate interventions may be planned. Hmong
      children (N = 335), ages 9-18 years participated in this study. A survey used
      Social Cognitive Theory (SCT) as the theoretical framework and silhouette drawing
      instrument. Heights and weights were measured and body mass indexes (BMIs) were
      calculated. About half of the children were either overweight (BMI >= 85th < 95th
      percentile) or obese (BMI >= 95th percentile). About 75% chose average sized
      silhouettes as healthiest and heaviest silhouettes as diabetic shape.
      Environmental influences including food availability, parents, and media
      influenced children's health perceptions. Results suggest a need for culturally
      appropriate interventions, aiming towards a child's environment and educating
      them about risks associated with obesity and diabetes.

PMID- 20686850
TI  - The size of an ethno-cultural community as a social determinant of health for
      Chinese seniors.
AB  - The present study investigated the link between the sizes of the Chinese
      community to the health of Chinese seniors in Canada. A secondary data analysis
      of survey data from a representative sample of 2,272 Chinese older adults aged 55
      and over was conducted. Hierarchical regression analyses were performed to assess
      the effects of the size of Chinese communities in Chinese seniors' health.
      Chinese seniors residing in the community with a small Chinese population
      reported better physical and mental health than the Chinese seniors residing in
      communities with a larger Chinese population. The findings were contrary to
      expectations that health of Chinese seniors should be higher in cities with large
      Chinese communities. These findings raise new questions for future investigations
      into the dynamics and impact of ethnic community size, and the importance of
      studying intragroup differences within ethno-cultural groups to better understand
      health disparities in ethnic groups.

PMID- 20686851
TI  - Disparities in access to HIV prevention among men of Mexican descent living in
      the Midwestern United States.
AB  - Men of Mexican descent (MMD) in the U.S. are disproportionately affected by HIV.
      Understanding MMD's access to HIV prevention is necessary to reduce their
      transmission rates. We explored disparities in access to HIV prevention among MMD
      of different assimilation status, healthcare access, and sexual risk behavior.
      322 Midwestern MMD completed a survey assessing their access to passive
      interventions (e.g., lectures), interactive interventions (e.g., counseling), HIV
      testing, media information, and information from the Internet. 64% MMD had
      received passive interventions, 36% interactive interventions, 42% HIV testing,
      41% information from media, and 12% from the Internet. MMD who were less
      assimilated to the U.S., had lower healthcare access, and were at risk for HIV,
      were less likely to have accessed prevention interventions but more likely to
      have received media information. Access to HIV prevention among Midwestern MMD is
      tied to their assimilation and healthcare access. Findings have implications for
      developing strategies of intervention delivery.

PMID- 20686852
TI  - Moving prevention research forward.

PMID- 20686853
TI  - Functional assessment of coronary artery flow using adenosine stress dual-energy
      CT: a preliminary study.
AB  - We attempted to assess coronary artery flow using adenosine-stress and dual
      energy mode with dual-source CT (DE-CT). Data of 18 patients with suspected
      coronary arteries disease who had undergone cardiac DE-CT were retrospectively
      analyzed. The patients were divided into two groups: 10 patients who performed
      adenosine stress CT, and 8 patients who performed rest CT as controls. We
      reconstructed an iodine map and composite images at 120 kV (120 kV images) using
      raw data with scan parameters of 100 and 140 kV. We measured mean attenuation in
      the coronary artery proximal to the distal portion on both the iodine map and 120
      kV images. Coronary enhancement ratio (CER) was calculated by dividing mean
      attenuation in the coronary artery by attenuation in the aortic root, and was
      used as an estimate of coronary enhancement. Coronary stenosis was identified as
      a reduction in diameter of >50% on CT angiogram, and myocardial ischemia was
      diagnosed by adenosine-stress myocardial perfusion scintigraphy. The iodine map
      showed that CER was significantly lower for ischemic territories (0.76 +/- 0.06)
      or stenosed coronary arteries (0.77 +/- 0.06) than for non-ischemic territories
      (0.95 +/- 0.21, P=0.02) or non-stenosed coronary arteries (1.07 +/- 0.33,
      P<0.001). The 120 kV images showed no difference in CER between these two groups.
      Use of CER on the iodine map separated ischemic territories from non-ischemic
      territories with a sensitivity of 86% and a specificity of 75%. Our
      quantification is the first non-invasive analytical technique for assessment of
      coronary artery flow using cardiac CT. CER on the iodine map is a candidate
      method for demonstration of alteration in coronary artery flow under adenosine
      stress, which is related to the physiological significance of coronary artery
      disease.

PMID- 20686854
TI  - MRI for detection of anomalous pulmonary venous drainage in patients with sinus
      venosus atrial septal defects.
AB  - Purpose of this survey was to estimate the value of MRI for the assessment of the
      anatomical and functional features of sinus venosus atrial septal defect (SVD).
      This prospective study included 13 surgically proven cases of SVD out of 81
      subjects submitted to MRI due to inconclusive transthoracic echocardiography
      (TTE) or suspicion of high intracardiac and/or extracardiac shunt volumes based
      on echocardiographic findings. MRI examination included cine SSFP sequences,
      contrast-enhanced 3D gradient-echo (GE) sequences for MR angiography (MRA) and
      phase-contrast flow-measurements. MRI revealed nine patients with a superior and
      four with an inferior SVD. Anomalous pulmonary venous drainage (APVD) was
      observed only in subjects with a superior SVD, and it was right-sided in all
      cases. All MRI and MRA results for the SVD patients were confirmed
      intraoperatively. The Correlation coefficient between MR flow measurements and
      cardiac catheterisation was 0.94 (P<0.0001). According to MRI the rest of the
      subjects (n=68) presented a secundum ASD, whereas in 18% an APVD coexisted. The
      latter MR outcomes concurred with the cardiac catheterisation (n=56) and
      operative (n=12) results. MRI provides a reliable, non-invasive method for
      evaluation of SVDs, APVDs and shunt quantification.

PMID- 20686855
TI  - The use of cellular magnetic resonance imaging to track the fate of iron-labeled
      multipotent stromal cells after direct transplantation in a mouse model of spinal
      cord injury.
AB  - PURPOSE: The objective of this study was to track the fate of iron-labeled,
      multipotent stromal cells (MSC) after their direct transplantation into mice with
      spinal cord injuries using magnetic resonance imaging (MRI). PROCEDURES: Mice
      with spinal cord injuries received a direct transplant of (1) live MSC labeled
      with micron-sized iron oxide particles (MPIO); (2) dead, MPIO-labeled MSC; (3)
      unlabeled MSC; or (4) free MPIO and were imaged at 3 T for 6 weeks after
      transplantation. RESULTS: Live, iron-labeled MSC appeared as a well-defined
      region of signal loss in the mouse spinal cord at the site of transplant.
      However, the MR appearance of dead, iron-labeled MSC and free iron particles was
      similar and persisted for the 6 weeks of the study. CONCLUSIONS: Iron-labeled
      stem cells can be detected and monitored in vivo after direct transplantation
      into the injured spinal cord of mice. However, the fate of the iron label is not
      clear. Our investigation indicates that caution should be taken when interpreting
      MR images after direct transplantation of iron-labeled cells.

PMID- 20686857
TI  - Functional phenotyping of the maternal albumin turnover in the mouse placenta by
      dynamic contrast-enhanced MRI.
AB  - PURPOSE: The purpose of this study was to develop a tool for functional
      phenotyping of the maternal circulation in the mouse placenta. PROCEDURES: In
      utero macromolecular dynamic contrast-enhanced magnetic resonance imaging (DCE
      MRI) was performed on embryonic day 10.5 (E10.5), E13.5, and E18.5. Fluorescence
      analysis was also used for validation of the results. RESULTS: The initial rate
      of contrast enhancement revealed an increased maternal blood volume fraction as
      the pregnancy progressed. Serial imaging of E10.5 and E13.5 placentas revealed a
      loss of contrast enhancement due to phagocytic uptake. A key application of
      macromolecular DCE-MRI would be to follow mouse pregnancies during fetal and
      placental manipulation including embryo transfer, tetraploid complementation, and
      fetal resorptions. We were able to resolve strain differences in ICR outbred mice
      carrying both ICR and C57Bl/6J embryos and to differentiate in utero resorptions
      from functional placentas. CONCLUSIONS: Our results highlight the importance of
      the functional in utero analysis of placental vascularization in physiological
      phenotyping of transgenic mice and suggest MRI, particularly macromolecular DCE
      MRI, as a non-invasive tool for the analysis of the placenta.

PMID- 20686856
TI  - Biodistribution, pharmacokinetics, and nuclear imaging studies of 111In-labeled
      rGel/BLyS fusion toxin in SCID mice bearing B cell lymphoma.
AB  - PURPOSE: We examined the biodistribution and pharmacokinetics of (111)In-labeled
      rGel/BLyS, a gelonin toxin (rGel)-B lymphocyte stimulator (BLyS) fusion protein.
      MATERIALS AND METHODS: rGel/BLyS was labeled with In-111 through DTPA with a
      labeling efficiency >95%. Biodistribution/imaging studies were obtained in severe
      combined immunodeficiency mice bearing diffuse large B cell lymphoma OCI-Ly10.
      Pharmacokinetic studies were performed in BALB/c mice. RESULTS: In vitro, DTPA
      conjugated rGel/BLyS displayed selective cytotoxicity against OCI-Ly10 cells and
      mantle cell lymphoma JeKo cells. In vivo, rGel/BLyS exhibited a tri-exponential
      disposition with a rapid initial mean distribution followed by an extensive mean
      distribution and a long terminal elimination phase. At 48 h after injection,
      uptake of the radiotracer in tumors was 1.25 %ID/g, with a tumor-to-blood ratio
      of 13. Tumors were clearly visualized at 24-72 h post-injection. Micro-SPECT-CT
      images and ex vivo analyses confirmed the accumulation of rGel/BLyS in OCI-Ly10
      tumors. CONCLUSIONS: (111)In-DTPA-rGel/BLyS are distributed to B cell tumors and
      induce apoptosis in tumors. Preclinical antitumor studies using rGel/BLyS should
      use a twice-per-week treatment schedule.

PMID- 20686858
TI  - Localization of deoxyglucose and annexin A5 in experimental atheroma correlates
      with macrophage infiltration but not lipid deposition in the lesion.
AB  - PURPOSE: The aim of this study was to understand the relationship of lipid
      deposition to the macrophage content, macrophage metabolism, and apoptosis in
      plaque. We compared the uptake of 2-deoxy-2-fluoro-D-[(14)C]glucose ([(14)C]FDG)
      and [(99m)Tc]HYNIC-annexin V ([(99m)Tc]annexin A5) with the lesion histology in
      apolipoprotein E knockout (apoE(-/-)) mice. PROCEDURES: Male apoE(-/-) mice (n =
      9) were injected with [(14)C]FDG and [(99m)Tc]annexin A5. Cryostat sections of
      aorta samples (n = 49) were used for dual-tracer autoradiography, and regional
      tracer uptake levels were evaluated. Lesions were identified histologically with
      Movat's pentachrome (AHA lesion phenotypes), Mac-2 staining (macrophage
      infiltration) and Oil Red O staining (lipid deposition). RESULTS: The highest
      uptakes of [(14)C]FDG (3.10 +/- 1.50 %ID * kilogram per square millimeter) and
      [(99m)Tc]annexin A5 (0.49 +/- 0.20 %ID * kilogram per square millimeter) were
      shown in atheromatous lesions (types III and IV). Each tracer uptake showed
      better correlation with macrophage infiltration than lipid deposition
      ([(14)C]FDG, r = 0.44 vs. r = 0.14; [(99m)Tc]annexin A5, r = 0.65 vs. r = 0.48).
      CONCLUSIONS: Both tracers were concentrated in type III and IV atheromatous
      lesions which corresponded to macrophage infiltration rather than lipid
      deposition.

PMID- 20686859
TI  - Quantitation in bioluminescence imaging by correction of tissue absorption for
      experimental oncology.
AB  - PURPOSE: We have developed a method of quantitation for correcting tissue
      absorption in in vivo bioluminescence imaging (BLI). PROCEDURES: Variations of
      luciferin emission spectrum were determined and were related to photon absorption
      to determine a correction curve. This was validated by combining BLI with
      tomoscintigraphy and tomodensitometry, which were applied to a lymphoma model.
      RESULTS: Tissue absorption affects luciferin emission spectrum, mainly for
      wavelengths less than 620 nm. So, we have selected two filters bordering 620 nm
      to quantify spectral modifications. A significant correlation was obtained
      between the spectral analysis and the percentage of transmitted light through
      tissues (R(2) = 0.97). On a disseminated tumour model, we have shown that such a
      methodology is of great interest to compare bioluminescent signals and to get
      more accurate quantitative data about tumour proliferation. CONCLUSIONS: Spectral
      analysis allows improved quantitation of BLI and could be of value to perform
      pharmacological studies and to follow tumour progression in models with tumours
      evolving in different locations.

PMID- 20686861
TI  - [Not Available].

PMID- 20686860
TI  - Visual analogical well-being scale for sleep apnea patients: validity and
      responsiveness : a test for clinical practice.
AB  - INTRODUCTION: Health-related quality-of-life (HRQL) tests used in sleep apnea
      hypopnea syndrome (SAHS) are time-consuming, complicating their application in
      clinical practice. The objective was to examine the validity and responsiveness
      of a simple visual analogical well-being scale (VAWS) for the clinical use.
      METHOD: The subjects proceed from a cohort of SAHS patients treated with CPAP for
      12 weeks. We correlated the VAWS with other HRQL tests, related clinical and
      polysomnographic measures to concurrent and construct validities. Responsiveness
      by: (1) comparison of HRQL tests between before and after treatment and effect
      size. (2) Association of the change with treatment between VAWS with other HRQL
      tests and between VAWS with clinical parameters. RESULTS: At baseline, VAWS
      correlated with all HRQL tests but better with functional outcomes in sleep
      questionnaires (FOSQ) and European quality-of-life questionnaire (EuroQol)
      thermometer. VAWS and FOSQ correlated better with clinical variables than other
      HRQL tests. VAWS captures the magnitude change with treatment similarly to FOSQ
      but better than other HRQL tests. CONCLUSION: VAWS is a very simple test which
      measures HRQL in SAHS. It could be a useful tool in clinical practice, primarily
      for the responsiveness of treatment.

PMID- 20686862
TI  - A Bayesian approach to probabilistic ecological risk assessment: risk comparison
      of nine toxic substances in Tokyo surface waters.
AB  - BACKGROUND, AIM, AND SCOPE: Quantitative risk comparison of toxic substances is
      necessary to decide which substances should be prioritized to achieve effective
      risk management. This study compared the ecological risk among nine major toxic
      substances (ammonia, bisphenol-A, chloroform, copper, hexavalent chromium, lead,
      manganese, nickel, and zinc) in Tokyo surface waters by adopting an integrated
      risk analysis procedure using Bayesian statistics. METHODS: Species sensitivity
      distributions of these substances were derived by using four Bayesian models.
      Environmental concentration distributions were derived by a hierarchical Bayesian
      model that explicitly considered the differences between within-site and between
      site variations in environmental concentrations. Medians and confidence intervals
      of the expected potentially affected fraction (EPAF) of species were then
      computed by the Monte Carlo method. RESULTS: The estimated EPAF values suggested
      that risk from nickel was highest and risk from zinc and ammonia were also high
      relative to other substances. The risk from copper was highest if bioavailability
      was not considered, although toxicity correction by a biotic ligand model greatly
      reduced the estimated risk. The risk from manganese was highest if a conservative
      risk index estimate (90% upper EPAF confidence limit) was selected. CONCLUSION:
      It is suggested that zinc is not a predominant risk factor in Tokyo surface
      waters and strategic efforts are required to reduce the total ecological risk
      from multiple substances. The presented risk analysis procedure using EPAF and
      Bayesian statistics is expected to advance methodologies and practices in
      quantitative ecological risk comparison.

PMID- 20686863
TI  - The use of olive tree (Olea europaea L.) leaves as a bioindicator for
      environmental pollution in the Province of Aydin, Turkey.
AB  - INTRODUCTION: In this study, olive tree leaves, collected from 50 sampling sites
      throughout the Province of Aydin, Turkey, were used to estimate level of
      pollution by measuring Al, As, B, Ba, Ca, Co, Cr, Cu, Fe, K, Li, Mg, Mn, Na, Ni,
      Pb, Sr, and Zn concentrations and calculating pollution factor (PF) values.
      MATERIALS AND METHODS: After sample preparation, collected leaves were microwave
      digested, and extracts were analyzed by an inductively coupled plasma-mass
      spectrometer. RESULTS AND DISCUSSION: The maximum PF values were >=10 for a
      number of elements ranging from 11-13 (Al, As, Cr, Fe, Mn, Ni) to >100 for Cu,
      Li, and Na. Urban-rural and roadside-nonroadside concentration comparisons showed
      that some of the elements (As, Cu, and Pb) were at significantly higher levels on
      urban and/or roadside sampling sites. SUMMARY AND CONCLUSION: Correlations and
      factor analysis showed that there may be common sources for some elements, which
      included several soil types and anthropogenic activities. Based on the results of
      the statistical source apportionment, possible sources were narrowed down with
      help of the constructed elemental concentration maps. In conclusion, utilization
      of olive tree leaves for biomonitoring and assessment of environmental pollution
      was shown to be possible in the Mediterranean region where they are indigenous
      and cultivated.

PMID- 20686864
TI  - Methyl jasmonate-induced enhancement of expression activity of Am-FaPS-1, a
      putative farnesyl diphosphate synthase gene from Aquilaria microcarpa.
AB  - A cDNA clone, designated Am-FaPS-1 (1310 bp), was isolated from callus culture
      derived from the leaf tissues of Aquilaria microcarpa. This gene contains an open
      reading frame encoding the protein of 342 amino acid residues with high homology
      to farnesyl diphosphate synthase from various plant sources. An appreciable
      increase in the transcriptional level of Am-FaPS-1 was reproducibly observed by
      the exposure of the cell culture to methyl jasmonate. The expression activity of
      the gene was also elevated when the cells were treated with yeast extract and
      Ca(2+)-ionophore A23187. These results suggest that Am-FaPS-1 and its translate
      play roles in methyl jasmonate- and yeast extract-induced responses of A.
      microcarpa, and Ca(2+) functions as an important messenger molecule in these
      processes. This set of the results would support our hypothesis that the
      activation of Ca(2+)-cascade evoked by the elevation of cytoplasmic Ca(2+)
      concentration is an essential early event in methyl jasmonate-induced responses
      of higher plant cells.

PMID- 20686865
TI  - Aromatic compounds and their antioxidant activity of Acer saccharum.
AB  - A new lignan glycoside, 5-(3",4"-dimethoxy-phenyl)-3-hydroxy-3-(4'-hydroxy-3'
      methoxybenzyl)-4-hydroxymethyl-dihydrofuran-2-one 4'-O-alpha-L: -rhamnopyranoside
      (1), with seven known compounds, compound 2, koaburside, icariside E(4),
      cleomiscosin C, cleomiscosin D, scopoletin, and 5'-demethylaquillochin, were
      isolated from the EtOH extract of the wood of Acer saccharum (Aceraceae). Their
      structures were determined by 1D and 2D nuclear magnetic resonance (NMR) and mass
      spectroscopy analysis. All of the isolated compounds, 1-8, were tested for their
      antioxidant activity in superoxide dismutase (SOD)-like assay.

PMID- 20686866
TI  - Polymorphisms in the genes encoding TGF-beta1, TNF-alpha, and IL-6 show
      association with type 1 diabetes mellitus in the Slovak population.
AB  - Numerous cytokines have been shown to participate in the pathogenesis of type 1
      diabetes (T1D). As gene polymorphisms can influence cytokine production or
      function, they may potentially contribute to genetic predisposition to the
      disease. The aim of this study was therefore to investigate the role of 22 single
      nucleotide polymorphisms (SNPs) in 13 cytokine and cytokine receptor genes in
      genetic susceptibility to T1D. Polymerase chain reaction with sequence-specific
      primers was used to genotype cytokine SNPs and HLA-DRB1 alleles in 151 diabetics
      and 140 healthy individuals of Slovak origin. Univariate analysis showed that
      transforming growth factor (TGF)-beta1 codon 10 TT homozygotes were significantly
      more susceptible to developing T1D than C allele carriers (P (c) = 0.0066, OR =
      2.46). Furthermore, tumor necrosis factor (TNF)-alpha -308 A allele carriers were
      also significantly overrepresented among the diabetics (P (c) = 0.0031, OR =
      2.62); however, the association of the -308 A allele with T1D might be due to its
      strong linkage disequilibrium with the susceptibility allele HLA-DRB1*0301. An
      association was also found with interleukin (IL)-6 -174 G/C and nt565 G/A SNPs;
      however, its significance was lost when statistical correction was applied. These
      data suggest that the TGF-beta1 codon 10 SNP is among numerous genetic variations
      with small individual effects on T1D development. Moreover, a possible role of
      TNF-alpha and IL-6 SNPs cannot be ruled out, although their association with T1D
      was due to strong LD with the HLA class II susceptibility allele or did not
      withstand statistical correction, respectively.

PMID- 20686868
TI  - Isomerization of 9c11t/10t12c CLA in triacylglycerols.
AB  - Isomers of conjugated linoleic acid from 7t9c through 12t14t can be induced by
      thermal treatment of triacylglycerol samples of 9c11t or 10t12c fatty acids in
      glass tubes. The formation of conjugated linoleic acids (CLAs) has been observed
      during thermal induction of the above-mentioned triacylglycerols at 250, 280 and
      320 degrees C. The concentrations of isomers formed in the mixture varied
      depending on the temperature and duration of the heating experiments. The
      objective of this study was to find a suitable thermal induction temperature and
      time that can produce most of the isomers of CLAs from the above-mentioned
      triacylglycerols. Such a mixture would give researchers a reference standard that
      can be used in the identification of CLAs in GC analyses of relevant samples.
      Fifteen-microlitre portions of the triacylglycerol samples containing
      9c11t/10t12c fatty acid were placed in micro-glass ampoules, sealed under
      nitrogen and then subjected to thermal treatment. The glass ampoules were removed
      at regular time intervals, cut open, and part of the samples was analysed by
      infrared spectroscopy using attenuated internal reflectance technique. The
      remainder of the samples was subjected to derivatisation into their methyl
      esters. The methyl esters of the isomerised fatty acids were then analysed by gas
      chromatography after appropriate dilution in heptane. The results show that the
      thermally induced glyceride samples of 9c11t/10t12c fatty acids gave CLA profiles
      containing isomers ranging from 7t9c to 12t14t. However, the concentrations of
      the isomers are different depending on the duration of the thermal induction. It
      appears that [1,5] sigmatropic rearrangements and positional isomerisations take
      place in the heated mixtures. The rearrangements and positional isomerisations
      are accelerated by increasing temperature. The glyceride samples heated to 325
      degrees C form isomers within 30 min and provide a mixture of CLA isomers that
      can be used as reference sample containing the methyl esters of CLAs.

PMID- 20686867
TI  - Enhanced aortic macrophage lipid accumulation and inflammatory response in LDL
      receptor null mice fed an atherogenic diet.
AB  - The effect of an atherogenic diet on inflammatory response and elicited
      peritoneal macrophage (Mphi) cholesterol accumulation in relation to aortic
      lesion formation was assessed in LDL receptor null (LDLr-/-) mice. Mice were fed
      an atherogenic or control diet for 32 weeks. The atherogenic relative to control
      diet resulted in significantly higher plasma monocyte chemoattractant protein-1
      (MCP-1), tumor necrosis factor alpha (TNFalpha) and interleukin-6 (IL-6)
      concentrations, more aortic wall Mphi deposition, higher serum non HDL
      cholesterol concentrations and total cholesterol to HDL-cholesterol ratios, and
      greater accumulation of both aortic free and esterified cholesterol. Elicited
      peritoneal Mphi selectively accumulated longer chain unsaturated fatty acids in
      their membrane, independent of the dietary fatty acid profile. Elicited
      peritoneal Mphi isolated from mice fed the atherogenic relative to control diet
      had significantly less arachidonic acid levels, accumulated significantly higher
      esterified cholesterol, had significantly higher mRNA levels and secretion of MCP
      1, and mRNA and protein levels of ATP-binding cassette A1. Diet treatment had no
      significant effect in elicited peritoneal Mphi on TNFalpha and IL-6 mRNA levels
      and secretion. These data suggest that the atherogenic relative to control diet
      resulted in higher plasma inflammatory factor concentrations, less favorable
      lipoprotein profile, higher elicited peritoneal Mphi cholesterol accumulation and
      inflammatory factor secretion, and more aortic wall Mphi deposition, which in
      turn were associated with greater aortic cholesterol accumulation.

PMID- 20686869
TI  - "Ain't no one here but us social forces": constructing the professional
      responsibility of engineers.
AB  - There are many ways to avoid responsibility, for example, explaining what happens
      as the work of the gods, fate, society, or the system. For engineers,
      "technology" or "the organization" will serve this purpose quite well. We may
      distinguish at least nine (related) senses of "responsibility", the most
      important of which are: (a) responsibility-as-causation (the storm is responsible
      for flooding), (b) responsibility-as-liability (he is the person responsible and
      will have to pay), (c) responsibility-as-competency (he's a responsible person,
      that is, he's rational), (d) responsibility-as-office (he's the responsible
      person, that is, the person in charge), and (e) a responsibility-as-domain-of
      tasks (these are her responsibilities, that is, the things she is supposed to
      do). For all but the causal sense of responsibility, responsibility may be taken
      (in a relatively straightforward sense)-and generally is. Why then would anyone
      want to claim that certain technologies make it impossible to attribute
      responsibility to engineers (or anyone else)? In this paper, I identify seven
      arguments for that claim and explain why each is fallacious. The most important
      are: (1) the argument from "many hands", (2) the argument from individual
      ignorance, and (3) the argument from blind forces. Each of these arguments makes
      the same fundamental mistake, the assumption that a certain factual situation,
      being fixed, settles responsibility, that is, that individuals, either
      individually or by some group decision, cannot take responsibility. I conclude by
      pointing out the sort of decisions (and consequences) engineers have explicitly
      taken responsibility for and why taking responsibility for them is rational, all
      things considered. There is no technological bar to such responsibility.

PMID- 20686870
TI  - Evaluation of status of zinc, copper, and iron levels in biological samples of
      normal children and children with night blindness with age groups of 3-7 and 8-12
      years.
AB  - The causes of night blindness in children are multifactorial, and particular
      consideration has been given to childhood nutritional deficiency, which is the
      most common problem found in underdeveloped countries. Such deficiency can result
      in physiological and pathological processes that in turn influence hair
      composition. This study was designed to compare the levels of zinc (Zn), copper
      (Cu), and iron (Fe) in scalp hair, blood, and urine of both genders of children
      with night blindness with age range of 3-7 and 8-12 years, comparing them to sex-
      and age-matched controls. A microwave-assisted wet acid digestion procedure was
      developed as a sample pretreatment, for the determination of zinc, copper, and
      iron in biological samples of children with night blindness. The proposed method
      was validated by using conventional wet digestion and certified reference samples
      of hair, blood, and urine. The digests of all biological samples were analyzed
      for Cu, Fe, and Zn by flame atomic absorption spectrometry using an air/acetylene
      flame. The results indicated significantly lower levels of Fe, Cu, and Zn in the
      biological samples (blood and scalp hair) of male and female children with night
      blindness, compared with control subjects of both genders. These data present
      guidance to clinicians and other professionals investigating the deficiency of
      essential trace metals in biological samples (scalp hair and blood) of children
      with night blindness.

PMID- 20686871
TI  - High-level production of MSH2 from Arabidopsis thaliana: a DNA mismatch repair
      system key subunit.
AB  - Biochemical and immunological information concerning DNA mismatch repair proteins
      from higher plants is currently limited, probably due to their low abundance in
      vivo. An initial analysis of AtMSH2 gene expression by quantitative real-time RT
      PCR indicates that calli and seedlings contain 96.7 and 1.4 cDNA copies per ng
      RNA, respectively, confirming that this gene is predominantly expressed in
      rapidly dividing tissues. In order to obtain large quantities of AtMSH2, the
      protein was efficiently expressed in an Escherichia coli system. The expressed
      gene product has an in-frame N-terminal Trx-His(6)-S-tag. The fusion protein
      represents about 11% of the soluble protein from IPTG-induced E. coli cells.
      After a two-step purification procedure the final yield accounts for 0.7 mg/g
      cells. Digestion of this electrophoretically homogeneous recombinant protein with
      enterokinase results in an intact protein with only one extra amino acid
      introduced at the N-terminal end. Purified intact protein was used to induce
      polyclonal antibodies in rabbits. These antibodies cross-react with a 110-kDa
      protein from cauliflower inflorescences. Together, our data describe the
      transcript level, cloning, expression, purification, and polyclonal antibody
      preparation of AtMSH2. This work will surely be useful for carrying out plant
      mismatch repair assays in vitro and analyzing protein expression after the
      exposure of plants to various stresses.

PMID- 20686872
TI  - A 2010 evidence-based algorithm for the pharmacotherapy of social anxiety
      disorder.
AB  - A growing evidence base on the management of social anxiety disorder has yielded
      many meta-analyses and guidelines on the pharmacotherapy of this clinically
      important condition. We aimed to update a pharmacotherapy algorithm for the
      treatment of social anxiety disorder that was developed to be concise and user
      friendly and that was addressed to the primary care practitioner in particular.
      The updated algorithm attempts to summarize succinctly the recent literature in
      this area, as well as to include the views of an international panel of experts
      with diverse experience. The algorithm comprises eight sequential steps,
      beginning with those focused on diagnosis and initiating treatment and ending
      with the management of the treatment-refractory patient.

PMID- 20686873
TI  - Age-related changes in the corpus callosum in early-onset bipolar disorder
      assessed using volumetric and cross-sectional measurements.
AB  - Corpus callosum (CC) area abnormalities have been reported in magnetic resonance
      imaging (MRI) studies of adults and youths with bipolar disorder (BPD),
      suggesting interhemispheric communication may be abnormal in BPD and may be
      present early in the course of illness and affect normal neuromaturation of this
      structure throughout the lifecycle. Neuroimaging scans from 44 youths with DSM-IV
      BPD and 22 healthy controls (HC) were analyzed using cross-sectional area
      measurements and a novel method of volumetric parcellation. Univariate analyses
      of variance were conducted on CC subregions using both volume and traditional
      area measurements. Youths with BPD had smaller middle and posterior callosal
      regions, and reduced typical age-related increases in CC size. The cross
      sectional area and novel volumetric methodologies resulted in similar findings.
      Future longitudinal assessments of CC development would track the evolution of
      callosal abnormalities in youths with BPD and allow exploration of the functional
      significance of these findings.

PMID- 20686874
TI  - Clinical trial report-real-time in vivo polyp histology diagnosis: implications
      for the practice of colonoscopy.

PMID- 20686875
TI  - Deception within adolescent sexual conduct.
AB  - Deception is presented as a "design to defeat a design" (Thompson 1986, p 64)
      where one actor purposefully changes the environment with the intention on
      generating a less adaptive response from another actor. The shared context
      combined with the indeterminacy of meanings makes deception not only possible,
      but also an important strategy for adaptation. In this regard not all deception
      temporarily causes individuals to reorganize their meaning making hierarchy
      around the changes made by the other party. Different uses of deceptions are
      explored with regards to adolescent sexual conduct, as their complex and quickly
      changing representations necessitate social recognition and adaptation.

PMID- 20686876
TI  - Reactivation of hepatitis D virus after chemotherapy for diffuse large B cell
      lymphoma despite lamivudine prophylaxis.
AB  - We describe a case of reactivation of hepatitis D virus (HDV) in a patient
      treated with chemotherapy for a diffuse large B cell lymphoma despite lamivudine
      prophylaxis. This case suggests that previously cleared HDV should be considered
      when administering chemotherapy to patients with lymphoma.

PMID- 20686877
TI  - Successful treatment of cryoglobulinemic glomerulonephritis derived from
      Waldenstrom's macroglobulinemia by rituximab-CHOP and tandem high-dose
      chemotherapy with autologous peripheral blood stem cell transplantation.
AB  - Waldenstrom's macroglobulinemia (WM) is a slowly progressive, low-grade B cell
      lymphoproliferative disorder. In contrast to the indolent progression, the
      development of cryoglobulinemic glomerulonephritis associated with WM is a rare,
      aggressive, and life-threatening complication. We describe the case of a 53-year
      old man who suffered from WM, which was accompanied by cryoglobulinemic
      glomerulonephritis. WM was diagnosed on the basis of an increase in monoclonal
      IgM kappa and infiltration of abnormal lymphoplasmacytic cells in the bone
      marrow. Moreover, the case was complicated by increase in the levels of urinary
      protein, serum creatinine, and serum cryoglobulin. Histological findings showed
      endocapillary glomerulonephritis with hyaline plugs. Electron microscopy
      demonstrated the accumulation of electron-dense deposits in the subepithelial,
      subendothelial, intramembranous, and mesangial areas, which revealed
      cryoglobulinemic proliferative glomerulonephritis. The patient received four
      courses of rituximab therapy followed by four courses of R-CHOP therapy
      (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) in
      combination with cryofiltration. Subsequently, the patient underwent high-dose
      chemotherapy (melphalan [L-PAM]) followed by tandem autologous peripheral blood
      stem cell transplantation. After these treatments, the patient remained disease
      free for 26 months. Histological findings of cryoglobulinemic glomerulonephritis
      were markedly improved after these treatments. Our case suggests that these
      treatments may be a feasible, safe, and effective strategy for critical
      cryoglobulinemic glomerulonephritis derived from WM.

PMID- 20686878
TI  - [Epidemiology of human schistosomiasis in Mauritania. The right bank of the
      Senegal River as model].
AB  - A study was performed to determine the transmission and prevalence of human
      schistosomiasis in the Mauritanian side of the Senegal River basin.
      Parasitological investigations by Kato-Katz and urine filtration conducted on
      1,259 school children indicated a mean prevalence of S. haematobium--29.0%, 25.9%
      and 34.3%, respectively, in the children of the lower, middle and high valley.
      Only the school children of the lower delta valley were infected by S. mansoni
      with a mean prevalence rate of 21.5%. The malacological investigations carried
      out in the water points of each visited village highlighted the presence of B.
      pfeifferi, B. senegalensis, B. globosus, B. umbilicatus, B. truncatus and B.
      forskalii. The last three species are announced for the first time in the
      Mauritanian side of the Senegal River. The laboratory snail infection experiments
      indicate that B. senegalensis and B. globosus are the most important intermediate
      hosts for S. haematobium in the Mauritanian side of the Senegal River basin.
      However, an incompatibility between the oasis strains of S. haematobium and the
      snails of the lower valley was noted. In the middle valley and high valley, the
      infection of the school children takes place during the rainy season, because of
      the creation of the temporary water points, in the lower valley; the transmission
      seems to be continuous.

PMID- 20686879
TI  - The CRP 1846T/T genotype is associated with a poor prognosis in patients with non
      small cell lung cancer.
AB  - C-reactive protein (CRP) is one of the acute-phase proteins produced
      predominantly by hepatocytes in response to inflammation, and it has been widely
      reported that CRP genetic polymorphism is a risk factor for cardiovascular
      disease and ischemic stroke. In addition, we previously showed that the CRP
      1846T/T genotype is related to lymph node metastasis in patients with esophageal
      cancer. In the present study, we investigated the correlation between CRP 1846C>T
      polymorphism and the clinicopathological characteristics of non-small cell lung
      cancer (NSCLC). The study participants were 146 Japanese patients who underwent
      curative surgery for NSCLC. DNA was extracted from tumor samples, and CRP1846C>T
      polymorphism was investigated using the polymerase chain reaction-restriction
      fragment length polymorphism method. We then correlated genotype with known
      clinicopathological factors. Five-year overall survival among patients with the
      CRP 1846T/T genotype was significantly lower than among those with the 1846C/C or
      C/T genotype (p = 0.002, p = 0.001; log-rank test). Multivariate Cox proportional
      hazard analysis revealed age, sex, pathological stage III, and 1846T/T (hazard
      ratio, 1.76; 95% confidence interval, 1.003-3.16; p = 0.049) to be independent
      factors affecting 5-year overall survival. These findings suggest the CRP 1846T/T
      genotype is an independent predictor of a poor prognosis in patients with NSCLC.

PMID- 20686880
TI  - Evaluation of polymer mucoadhesiveness by the use of acoustic spectroscopy.
AB  - An innovative and simple methodology has been developed and used for the
      evaluation of mucoadhesive properties of several polymers by means of sound speed
      measurements using high-resolution acoustic spectroscopy. In systems made of
      polymers in water, variations in hydration shell of polymeric chains determine
      changes of dispersions compressibility, and this phenomenon can be monitored by
      sound speed measurements. Four different polymers have been selected, namely PEG
      6000, Carbopol 974, HPMC K4M, and Pectin 200/USP, all characterised by very
      different mucoadhesive properties. Samples made of each polymer alone (0.3-1.0%
      w/w) or in mixture with mucin (mucin fixed at 1.0% w/w) in water were
      investigated while using high-resolution ultrasonic spectrometer at two different
      frequencies (5.2 and 8.2 MHz). Polymer-mucin interaction was evaluated comparing
      experimental sound speed values of polymer-mucin samples with their theoretical
      values derived from the addition of sound speeds obtained while analysing each
      component alone. Results demonstrated the ability of the acoustic method to
      discriminate between mucoadhesive and no mucoadhesive polymer-mucin dispersions
      and allowed also the comparison between their mucoadhesive strengths. The study
      has therefore demonstrated the potential of using high-resolution ultrasonic
      spectroscopy to evaluate the polymers' mucoadhesiveness, with the great advantage
      of testing small amount of samples even if opaque.

PMID- 20686881
TI  - Development of pH-sensitive insulin nanoparticles using Eudragit L100-55 and
      chitosan with different molecular weights.
AB  - Insulin is a polypeptide hormone and usually administered for treatment of
      diabetic patients subcutaneously. The aim of this study was to investigate the
      efficiency of enteric nanoparticles for oral delivery of insulin. Nanoparticles
      were formed by complex coacervation method using chitosan of various molecular
      weights. Nanoparticles were characterized by drug loading efficiency
      determination, particle size analysis, Scanning Electron Microscopy (SEM), Zeta
      potential and CD spectroscopy (Circular Dichrosim). The in vitro release studies
      were performed at pH 1.2 and 7.4. The drug loaded nanoparticles showed 3.38% of
      entrapment, loading efficiency of 30.56% and mean particle size of 199 nm. SEM
      studies showed that the nanoparticles are non-spherical. Zeta potential increased
      with increasing molecular weight of chitosan. The CD spectroscopy profiles
      indicated that the nano-encapsulation process did not significantly disrupt the
      internal structure of insulin; additionally, pH-sensitivity of nanoparticles was
      preserved and the insulin release was pH-dependent. These results suggest that
      the complex coacervation process using chitosan and Eudragit L100-55 polymers may
      provide a useful approach for entrapment of hydrophilic polypeptides without
      affecting their conformation.

PMID- 20686882
TI  - Molecular dynamics simulation using weak-coupling NOE distance restraining.
AB  - Application of the weak-coupling scheme to restrain the configurations of a
      molecular system to a set of NOE distance restraints is investigated using two
      test systems: (i) a 15-atom chain molecule with one distance restraint; and (ii)
      a protein molecule with hundreds of NOE distance restraints. Atom-atom distance
      restraining by the weak-coupling technique is possible, but this method does not
      produce as good results as the penalty function method normally used to maintain
      NOE distance restraints.

PMID- 20686883
TI  - Treatment of NOE constraints involving equivalent or nonstereoassigned protons in
      calculations of biomacromolecular structures.
AB  - Two modifications to the commonly used protocols for calculating NMR structures
      are developed, relating to the treatment of NOE constraints involving groups of
      equivalent protons or nonstereoassigned diastereotopic protons. Firstly, a
      modified method is investigated for correcting for multiplicity, which is
      applicable whenever all NOE intensities are calibrated as a single set and
      categorised in broad intensity ranges. Secondly, a new set of values for
      'pseudoatom corrections' is proposed for use with calculations employing 'centre
      averaging'. The effect of these protocols on structure calculations is
      demonstrated using two proteins, one of which is well defined by the NOE data,
      the other less so. It is shown that failure to correct for multiplicity when
      using 'r(-6) averaging' results in overly precise structures, higher NOE energies
      and deviations from geometric ideality, while failure to correct for multiplicity
      when using 'r(-6) summation' can cause an avoidable degradation of precision if
      the NOE data are sparse. Conversely, when multiplicities are treated correctly,
      r(-6) averaging, r(-6) summation and centre averaging all give closely comparable
      results when the structure is well defined by the data. When the NOE data contain
      less information, r(-6) averaging or r(-6) summation offer a significant
      advantage over centre averaging, both in terms of precision and in terms of the
      proportion of calculations that converge on a consisten result.

PMID- 20686884
TI  - Doubly sensitivity-enhanced 3D TOCSY-HSQC.
AB  - Recently, strategies for double sensitivity enhancement in heteronuclear three
      dimensional NMR experiments were introduced (Krishnamurthy, V.V. (1995) J. Magn.
      Reson., B106, 170-177; Sattler et al. (1995) J. Biomol. NMR, 6, 11-22; Sattler et
      al. (1995) J. Magn. Reson., B108, 235-242). Since a sensitivity enhancement of a
      factor 2(1/2) can be achieved for each indirect dimension, nD spectra can
      theoretically be enhanced up to a factor of 2(((n-1)/2)). We propose and analyze
      a doubly enhanced three-dimensional TOCSY-HSQC sequence. The application of the
      doubly enhanced three-dimensional {(15)N, (1)H} TOCSY-HSQC sequence is shown for
      uniformly (13)C-/(15)N- and (15)N-labeled samples of the relatively large
      Azotobacter vinelandii flavodoxin II (179 amino acids). The main factors that
      contribute to the final signal-to-noise enhancement have been systematically
      investigated. The sensitivity enhancement obtained for the doubly enhanced TOCSY
      HSQC pulse sequence as compared to the standard (unenhanced) version is close to
      the theoretically expected factor of two.

PMID- 20686885
TI  - An (H)C(CO)NH-TOCSY pulse scheme for sequential assignment of protonated methyl
      groups in otherwise deuterated (15)N, (13)C-labeled proteins.
AB  - A biosynthetic strategy has recently been developed for the production of (15)N,
      (13)C, (2)H-labeled proteins using (1)H(3)C-pyruvate as the sole carbon source
      and D(2)O as the solvent. The methyl groups of Ala, Val, Leu and Ile (gamma2
      only) remain highly protonated, while the remaining positions in the molecule are
      largely deuterated. An (H)C(CO)NH-TOCSY experiment is presented for the
      sequential assignment of the protonated methyl groups. A high-sensitivity
      spectrum is recorded on a (15)N, (13)C, (2)H, (1)H(3)C-labeled SH2 domain at 3
      degrees C (correlation time 18.8 ns), demonstrating the utility of the method for
      proteins in the 30-40 kDa molecular weight range.

PMID- 20686886
TI  - An approach to global fold determination using limited NMR data from larger
      proteins selectively protonated at specific residue types.
AB  - A combination of calculation and experiment is used to demonstrate that the
      global fold of larger proteins can be rapidly determined using limited NMR data.
      The approach involves a combination of heteronuclear triple resonance NMR
      experiments with protonation of selected residue types in an otherwise completely
      deuterated protein. This method of labelling produces proteins with alpha
      specific deuteration in the protonated residues, and the results suggest that
      this will improve the sensitivity of experiments involving correlation of side
      chain ((1)H and (13)C) and backbone ((1)H and (15)N) amide resonances. It will
      allow the rapid assignment of backbone resonances with high sensitivity and the
      determination of a reasonable structural model of a protein based on limited NOE
      restraints, an application that is of increasing importance as data from the
      large number of genome sequencing projects accumulates. The method that we
      propose should also be of utility in extending the use of NMR spectroscopy to
      determine the structures of larger proteins.

PMID- 20686888
TI  - Unilateral contractions modulate interhemispheric inhibition most strongly and
      most adaptively in the homologous muscle of the contralateral limb.
AB  - We investigated how volitional contractions affect interhemispheric inhibition
      (IHI) from the active to the passive hemisphere. Younger and older adults
      isometrically contracted their dominant thumb (abductor pollicis brevis, APB) to
      various force targets. In ballistic contraction trials, transcranial magnetic
      stimulation (TMS) was administered very shortly after the onset of APB activity.
      In tonic contraction trials, TMS was delivered while the target force was
      maintained. In control trials both thumbs remained quiescent. In all trials, a
      test stimulus (TS) was directed to the APB hotspot in the non-dominant hemisphere
      (130% left APB resting motor threshold, RMT). In half the trials, a conditioning
      stimulus (130% right APB RMT) was applied to the APB hotspot in the dominant
      hemisphere 10 ms prior to the TS. Targeted ballistic contractions of the right
      APB were found to modulate (increase) IHI measured in the left APB, as previously
      reported for tonic contractions. Furthermore, the extent of the IHI increase was
      found to scale with the strength of the contralateral ballistic or tonic
      contraction. Less pronounced, but statistically significant, IHI increases were
      also observed in the left abductor digiti minimi and extensor carpi radialis
      during right APB contraction. For these muscles, however, the extent of the IHI
      modulation was independent of APB contraction strength. The capacity to modulate
      inhibition during contractions was unaffected by advancing age. During volitional
      actions, the ability to modulate IHI most adaptively in the homologous muscle of
      the resting limb may contribute to the prevention of mirror movements.

PMID- 20686887
TI  - Perceived need for mental health care and barriers to care in the Netherlands and
      Australia.
AB  - PURPOSE: This study of Australian and Dutch people with anxiety or depressive
      disorder aims to examine people's perceived needs and barriers to care, and to
      identify possible similarities and differences. METHODS: Data from the Australian
      National Survey of Mental Health and Well-Being and the Netherlands Study of
      Depression and Anxiety were combined into one data set. The Perceived Need for
      Care Questionnaire was taken in both studies. Logistic regression analyses were
      performed to check if similarities or differences between Australia and the
      Netherlands could be observed. RESULTS: In both countries, a large proportion had
      unfulfilled needs and self-reliance was the most frequently named barrier to
      receive care. People from the Australian sample (N = 372) were more likely to
      perceive a need for medication (OR 1.8; 95% CI 1.3-2.5), counselling (OR 1.4; 95%
      CI 1.0-2.0) and practical support (OR 1.8; 95% CI 1.2-2.7), and people's overall
      needs in Australia were more often fully met compared with those of the Dutch
      sample (N = 610). Australians were more often pessimistic about the helpfulness
      of medication (OR 3.8; 95% CI 1.4-10.7) and skills training (OR 3.0; 95% CI 1.1
      8.2) and reported more often financial barriers for not having received (enough)
      information (OR 2.4; 95% CI 1.1-5.5) or counselling (OR 5.9; 95% CI 2.9-11.9).
      CONCLUSIONS: In both countries, the vast majority of mental health care needs are
      not fulfilled. Solutions could be found in improving professionals' skills or
      better collaboration. Possible explanations for the found differences in
      perceived need and barriers to care are discussed; these illustrate the value of
      examining perceived need across nations and suggest substantial commonalities of
      experience across the two countries.

PMID- 20686889
TI  - Differential effects of exogenous and endogenous cueing in multi-stream RSVP:
      implications for theories of attentional blink.
AB  - The attentional blink (AB) refers to the finding that performance on the second
      of two targets (T1 and T2) in a rapid serial visual presentation (RSVP) stream is
      impaired when the targets are presented within 200-500 ms. To explore the
      possible interaction between spatial attentional orienting and temporary
      attentional deficits, this study used central (endogenous) and peripheral
      (exogenous) cues in a multi-stream RSVP task and compared the endogenous and
      exogenous cueing effects inside and outside of the AB period. While the
      endogenous cueing effect was constant in magnitude over time, the exogenous
      cueing effect was significantly larger inside than outside of the AB period.
      Theoretical implications of these findings for the interaction between attention
      mechanisms in spatial and temporal domains are discussed.

PMID- 20686890
TI  - Muscimol inactivation caudal to the interstitial nucleus of Cajal induces hemi
      seesaw nystagmus.
AB  - Hemi-seesaw nystagmus (hemi-SSN) is a jerk-waveform nystagmus with conjugate
      torsional and disjunctive vertical components. Halmagyi et al. in Brain 117(Pt
      4):789-803 (1994), reported hemi-SSN in patients with unilateral lesions in the
      vicinity of the Interstitial Nucleus of Cajal (INC) and suggested that an
      imbalance in projections from the vestibular nuclei to the INC was the source of
      the nystagmus. However, this hypothesis was called into question by Helmchen et
      al. in Exp Brain Res 119(4):436-452 (1998), who inactivated INC in monkeys with
      muscimol (a GABA(A) agonist) and induced failure of vertical gaze-holding (neural
      integrator) function but not hemi-SSN. We injected 0.1-0.2 microl of 2% muscimol
      into the supraoculomotor area, 1-2 mm dorso-lateral to the right oculomotor
      nucleus and caudal to the right INC. A total of seven injections in two juvenile
      rhesus monkeys were performed. Hemi-SSN was noted within 5-10 min after injection
      for six of the injections. Around the time the hemi-SSN began, a small skew
      deviation also developed. However, there was no limitation of horizontal or
      vertical eye movements, suggesting that the nearby oculomotor nucleus was not
      initially compromised. Limitations in eye movement range developed about (1/2)-1
      h following the injections. Clinical signs that were observed after the animal
      was released to his cage included a moderate to marked head tilt toward the left
      (contralesional) side, consistent with an ocular tilt reaction. We conclude that
      hemi-SSN can be caused by lesions just caudal to the INC, whereas lesions of the
      INC itself cause down-beat nystagmus and vertical gaze-holding failure, as
      demonstrated by Helmchen et al. Combined deficits may be encountered with lesions
      that involve several midbrain structures.

PMID- 20686892
TI  - Two-phase uptake of nickel in the ground beetle Pterostichus oblongopunctatus
      (Coleoptera: Carabidae): implications for invertebrate metal kinetics.
AB  - We studied nickel (Ni) kinetics in the ground beetle Pterostichus
      oblongopunctatus exposed to different, potentially stressful, temperatures. We
      found unexpected Ni kinetics in metal-exposed adult and larval beetles. Instead
      of the pattern observed commonly for other metals, i.e., an increase in metal
      concentration followed by stabilisation in the uptake phase and a decrease after
      transfer to uncontaminated food, the Ni-fed beetles apparently switched to
      decontamination soon after the start of Ni exposure while they were still being
      fed Ni-spiked food. In addition, internal body Ni concentrations showed high
      variance. The traditional first-order, one-compartment model with the switch to
      decontamination set to the last day of the uptake phase appeared inadequate and
      in most cases was nonsignificant. Instead, the model with a regression-estimated
      point of switching to decontamination fit the data better, explaining 57.2-91.5%
      of the temporal variability of mean Ni body concentrations (weighted regression)
      in adult beetles and 44.1-62.3% in larvae. Temperature did not affect Ni
      toxicokinetics in adults, but in larvae there were some temperature-dependent
      differences in kinetic parameters.

PMID- 20686891
TI  - Eye-head coordination in the guinea pig I. Responses to passive whole-body
      rotations.
AB  - Vestibular reflexes act to stabilize the head and eyes in space during
      locomotion. Head stability is essential for postural control, whereas retinal
      image stability enhances visual acuity and may be essential for an animal to
      distinguish self-motion from that of an object in the environment. Guinea pig eye
      and head movements were measured during passive whole-body rotation in order to
      assess the efficacy of vestibular reflexes. The vestibulo-ocular reflex (VOR)
      produced compensatory eye movements with a latency of approximately 7 ms that
      compensated for 46% of head movement in the dark and only slightly more in the
      light (54%). Head movements, in response to abrupt body rotations, also
      contributed to retinal stability (21% in the dark; 25% in the light) but
      exhibited significant variability. Although compensatory eye velocity produced by
      the VOR was well correlated with head-in-space velocity, compensatory head-on
      body speed and direction were variable and poorly correlated with body speed. The
      compensatory head movements appeared to be determined by passive biomechanical
      (e.g., inertial effects, initial tonus) and active mechanisms (the vestibulo
      collic reflex or VCR). Chemically induced, bilateral lesions of the peripheral
      vestibular system abolished both compensatory head and eye movement responses.

PMID- 20686893
TI  - Optimal bearing surfaces for total hip replacement in the young patient: a meta
      analysis.
AB  - Although there is general consensus about the efficacy of total hip replacement
      (THR) in young patients, the most appropriate bearings in young patients remain
      highly debated. The three most popular bearings in use include metal-on
      polyethylene (MOP), metal-on-metal (MOM) and ceramic-on-ceramic (COC). We
      conducted a systematic review and meta-analysis of literature to summarise the
      best available evidence on relative success of the three most popular bearings
      used in THR in young active patients. Our findings support the use of MOM
      bearings in the management of the young arthritic hip. These findings, largely
      based upon observational studies, should be taken in the context of the
      limitations of such non-randomised study designs.

PMID- 20686895
TI  - The communicative potential of bat echolocation pulses.
AB  - Ecological constraints often shape the echolocation pulses emitted by bat
      species. Consequently some (but not all) bats emit species-specific echolocation
      pulses. Because echolocation pulses are often intense and emitted at high rates,
      they are potential targets for eavesdropping by other bats. Echolocation pulses
      can also vary within species according to sex, body size, age, social group and
      geographic location. Whether these features can be recognised by other bats can
      only be determined reliably by playback experiments, which have shown that
      echolocation pulses do provide sufficient information for the identification of
      sex and individual in one species. Playbacks also show that bats can locate
      conspecifics and heterospecifics at foraging and roost sites by eavesdropping on
      echolocation pulses. Guilds of echolocating bat species often partition their use
      of pulse frequencies. Ecology, allometric scaling and phylogeny play roles here,
      but are not sufficient to explain this partitioning. Evidence is accumulating to
      support the hypothesis that frequency partitioning evolved to facilitate
      intraspecific communication. Acoustic character displacement occurs in at least
      one instance. Future research can relate genetic population structure to regional
      variation in echolocation pulse features and elucidate those acoustic features
      that most contribute to discrimination of individuals.

PMID- 20686896
TI  - NF-kappaB related abnormal hyper-expression of iNOS and NO correlates with the
      inflammation procedure in biliary atresia livers.
AB  - OBJECTIVE: To study the expression of inducible nitric oxide synthase (iNOS) and
      its related regulators in biliary atresia (BA) livers and exlpore their
      relationships with the inflammation pathway in BA livers. METHOD: The iNOS
      expression in livers of 38 cases of BA children, 15 cases of neonatal cholestasis
      (NC) children, and 18 cases of normal control were, respectively, examined and
      total nitric oxide (NO) metabolites concentration of all samples were calculated
      by a colorimetric method based on Griess reaction. The TdT-mediated dupt biotin
      nick end labeling (TUNEL) method was used to label the apoptotic bile duct
      epithelial cells and hepatocytes. The western blotting and immunohistochemistry
      methods to semi-quantitatively analyze the nuclear factor-kappaB (NF-kappaB)
      expression of each group were also used. RESULTS: The iNOS expression intensity
      and total NO metabolites concentration of BA group (0.30 +/- 0.08, 90.40 +/-
      12.46 micromol/L) were significantly higher than those of NC and normal control
      groups, P < 0.01. Correlation analysis showed a strong positive correlation
      between the serum AST level (152.76 +/- 29.59 U/L) and total NO metabolites
      concentration in BA group. Compared with the NC (32.47 +/- 5.55) and normal
      control (20.72 +/- 5.63) groups, a significantly higher apoptosis rate of
      intrahepatic bile duct epithelial cells was found in BA group (54.00 +/- 11.67)
      that tightly correlated with the iNOS intensity (r = 0.99, P < 0.01). The NF
      kappaB intensity of BA group was also significantly higher than that of NC and
      normal control groups and had a strong positive correlation with the iNOS
      intensity (r = 0.97, P < 0.01). CONCLUSION: The abnormal hyper-expression of iNOS
      may play an important role in mediating the inflammation procedure in BA livers.
      This change perhaps has some relationship with the high expression of NF-kappaB
      and NO. These regulators can up-regulate the apoptosis of bile duct epithelial
      cells in BA livers and cause the damage to liver tissues.

PMID- 20686897
TI  - Malignant gastric teratoma: report of two cases from a single center.
AB  - Gastric teratomas (GT) are rare, accounting for less than 1% of all teratomas. GT
      usually presents with an abdominal mass, but rarely does it present with
      gastrointestinal bleeding also. Gastric teratomas are rarely malignant and only
      two cases are reported in the literature. We treated two cases of malignant GT
      (endodermal sinus tumor) in infants. Both the patients were male. Surgical
      excision was done in both the cases. One patient received adjuvant chemotherapy.
      Both the patients are surviving without recurrence after 5 and 6 years of
      surgical excision, respectively. Prognosis of GT is excellent even when it is
      malignant.

PMID- 20686899
TI  - Temperature-controlled radiofrequency tonsil ablation for the treatment of
      halitosis.
AB  - The objective of the study was to evaluate the efficacy and safety of temperature
      controlled radiofrequency (RF) tonsil ablation in the treatment of halitosis
      caused by chronic tonsillitis with caseum. The study method was retrospective.
      The medical records of 58 patients undergoing temperature-controlled RF tonsil
      ablation due to chronic tonsillitis with caseum between November 1, 2005 and
      November 30, 2008 were reviewed. Forty-nine (84.4%) of 58 patients reported
      complete disappearance of bad breath after the first treatment; five patients
      (8.6%) reported as having insufficient improvement and four (6.9%) patients had
      no change. Two patients from "insufficient group" and all four patients from "no
      change" group agreed to a repeat treatment. After the second session, four (6.9%)
      patients reported complete disappearance of halitosis with the disappearance of
      caseum formation. But two patients still suffered from halitosis. One of these
      patients underwent tonsillectomy, other patient is under our follow-up. Overall,
      complete elimination of halitosis was accomplished with one session in 49 (84.4%)
      patients, two sessions in four (6.9%) patients, making a total of 53 (91.3%)
      patients. Postoperative morbidities included one transient mild bleeding, one
      secondary bleeding and one mild edema. Temperature-controlled RF tonsil ablation
      is an effective method for treating halitosis which derived from chronic
      tonsillitis with caseum. This well-tolerated technique avoids the post-procedure
      morbidities and discomfort of more invasive surgical modalities currently used.

PMID- 20686898
TI  - Gastroschisis: an update.
AB  - Gastroschisis (GS) continues to increase in frequency, with several studies now
      reported an incidence of between 4 and 5 per 10,000 live births. The main risk
      factor would seem to be young maternal age, and it is in this group that the
      greatest increase has occurred. Whilst various geographical regions confer a
      higher risk, the impact of several other putative risk factors, including smoking
      and illicit drug use, may be less important than when first identified in early
      epidemiological studies. Over 90% of cases of GS will now be diagnosed on
      antenatal ultrasound, but its value in determining the need for early delivery
      remains unclear. There would appear no clear evidence for either routine early
      delivery or elective caesarean section for infants with antenatally diagnosed GS.
      Delivery at a centre with paediatric surgical facilities reduces the risk of
      subsequent morbidity and should represent the standard of care. The relative
      roles of primary closure, staged closure and ward reduction, with or without
      general anaesthesia, appear less clear with considerable variation between
      centres in both the use of these techniques and subsequent surgical outcomes.
      Survival rates continue to improve, with rates well in excess of 90% now routine.
      The limited long-term developmental data available would suggest that normal or
      near-normal outcomes may be expected although there remains a need for further
      studies.

PMID- 20686900
TI  - The effects of whole body vibration and exercise on fibrinolysis in men.
AB  - Whole body vibration (WBV) is a novel modality that has been demonstrated to
      enhance muscular and cardiovascular functions reported to increase fibrinolytic
      activity. The purpose of this study was to examine the fibrinolytic response to
      WBV and exercise in men. Twenty healthy males (23.8 +/- 0.9 years, 25.6 +/- 0.2
      kg m(-2)) participated in the study. Each subject performed three trials in
      randomized order separated by 1 week: exercise (X), vibration (V) and vibration +
      exercise (VX). Exercise sessions consisted of 15 min of unloaded squatting at a
      rate of 20 per minute. Vibration sessions were conducted on a WBV platform
      vibrating for 15 min. Tissue plasminogen activator (tPA) and plasminogen
      activator inhibitor (PAI-1) were assessed at baseline and immediately after each
      condition. The increase in tPA activity was significantly greater in VX (0.87 +/-
      0.35 to 3.21 +/- 1.06 IU ml(-1)) compared to X (0.71 +/- 0.36 to 2.4 +/- 1.13 IU
      ml(-1)) or V (0.83 +/- 0.25 to 1.00 +/- 0.37 IU ml(-1)) conditions, and greater
      in the X condition compared to the V condition. PAI-1 activity decreased
      significantly more in the VX (6.54 +/- 5.53 to 4.89 +/- 4.13 IU ml(-1)) and X
      (9.76 +/- 8.19 to 7.48 +/- 7.11 IU ml(-1)) conditions compared to the V (5.68 +/-
      3.53 to 5.84 +/- 3.52 IU ml(-1)) condition. WBV does not augment fibrinolytic
      activity in healthy men. However, WBV combined with squatting exercise increases
      fibrinolytic activity more than exercise alone.

PMID- 20686901
TI  - Does the number of sclerotised structures used for the systematics of monogeneans
      change with age? A study of the monocotylid Dendromonocotyle pipinna.
AB  - Although monogenean systematics is often based on the morphological analysis of
      sclerotised structures, their variation with size or age is rarely investigated.
      Two hundred specimens of the monocotylid Dendromonocotyle pipinna Chisholm and
      Whittington 2004 were studied. In the haptor, the numbers of marginal papillae,
      of sclerites in the marginal papillae and of sclerites in the septa did not
      change according to the size; however, the mean interval between the sclerites in
      the septa increased linearly with body length. This suggests that, at least in
      certain cases, valuable systematic descriptions can be made on incompletely grown
      monogeneans.

PMID- 20686902
TI  - Voiding urosonography with second-generation contrast agent versus voiding
      cystourethrography.
AB  - Contrast-enhanced voiding urosonography (VUS) is becoming more widely used for
      the diagnosis of vesicoureteric reflux (VUR). The purpose of this study was to
      evaluate the sensitivity of VUS using a second-generation ultrasound (US)
      contrast agent and compare it with standard fluoroscopic voiding
      cystourethrography (VCUG). A total of 183 children with 366 kidney-ureter units
      (KUUs) underwent VUS and VCUG in the same session with the same catheterization.
      VUS was performed after intravesical administration of 1 ml of a second
      generation ultrasound contrast agent (UCA; SonoVue, Bracco, Italy). VUR was
      detected in 140 out of 366 cases (38%); in 89 (24.3%) by both methods, in 37
      (10.1%) by VUS only, and in 14 (3.8%) by VCUG only. Although there was
      considerable agreement in the diagnosis of VUR by VUS and VCUG (kappa=0.68,
      standard error [kappa]=0.04), the difference in the detection rate of reflux
      between VUS and VCUG was significant (p<0.00001). The grade of VUR detected with
      VUS showed moderate agreement with grading by VCUG. Our findings suggest that
      contrast-enhanced harmonic VUS using a second-generation contrast agent is
      superior to VCUG in the detection and grading of VUR, and it should be the method
      of choice for this clinical indication.

PMID- 20686903
TI  - Liver transplantation in oxalosis prior to advanced chronic kidney disease.
AB  - While curative of the disease, combined kidney and liver transplantation (K/LTx)
      for primary hyperoxaluria type 1 (PH1) continues to carry with it a risk for
      patient death of 15-25%, which over time may not differ from that of kidney
      transplantation alone (KTx). In this editorial, survival data are reviewed as
      well as the limited data available for kidney graft function, which may favor
      K/LTx in the short term but is more uncertain in the longer term. The window of
      opportunity that favors preemptive K/LTx is relatively narrow and is likely even
      narrower for preemptive isolated LTx. Capability and experience in the medical
      management of such patients, and the opportunities available, as well as likely
      patient compliance, so far without supporting data, may be the most important
      determination of the best strategy for management.

PMID- 20686904
TI  - A Japanese case series of 12 patients with esophageal eosinophilia.
AB  - BACKGROUND: Eosinophilic esophagitis (EoE) has been a rarely recognized condition
      in Asian populations, and its clinical manifestation is rarely documented. Our
      aim was to describe clinically, endoscopically, and pathologically the features
      of patients with esophageal eosinophilia, including EoE. METHODS: Twelve patients
      histologically proven to have esophageal eosinophilia were investigated. The
      histological diagnostic cutoff value was defined as a peak of >=15
      eosinophils/high-power field (HPF) in esophageal biopsies. Symptoms, endoscopic
      and pathological findings, and treatment outcome were evaluated. RESULTS: Nine of
      the 12 patients were male and the 12 patients had a mean age of 47.7 years.
      Allergic conditions were concurrent in a total of 3 patients. Mild peripheral
      eosinophilia was observed in only 2 patients. The predominant symptom was solid
      food dysphagia, but some patients complained of heartburn, or chest, epigastric,
      or back pain. Three asymptomatic subjects were also incidentally diagnosed during
      endoscopic screening. Linear furrows, concentric rings, and white exudates in the
      esophagus were frequently observed. In 4 of 5 patients who were administered a
      proton pump inhibitor (PPI), esophageal eosinophilia was histologically decreased
      or disappeared with symptom relief and endoscopic improvement. In 2 patients
      unresponsive to PPI, topical steroid therapy, administered by the swallowing of
      fluticasone propionate, led to symptomatic and histological remission.
      CONCLUSIONS: The endoscopic recognition of linear furrows, concentric rings, and
      white exudates is important in the diagnosis of eosinophilic esophageal
      inflammation. In a subset of patients this condition improves
      clinicopathologically with PPI treatment, and typical EoE, as strictly defined by
      unresponsiveness to PPI, appears to be a rather rare condition.

PMID- 20686905
TI  - Effects of atypical antipsychotics and haloperidol on PC12 cells: only
      aripiprazole phosphorylates AMP-activated protein kinase.
AB  - By converting changes in intracellular energy status to changes in cell membrane
      polarization, ATP-sensitive K(+) (K(ATP)) channels in hypothalamic appetite
      regulating neurons play a critical role in linking neuronal electrochemical
      function, metabolic and energy status, and feeding behavior. Most atypical
      antipsychotics (AAPs) increase the appetite of patients with schizophrenia and
      thus cause obesity. This study aimed to explain the mechanism underlying AAP
      induced appetite stimulation, based on the fact that the efficiency of fatty acid
      uptake into mitochondria generating ATP through beta-oxidation is determined by
      the rate of fatty acid synthesis. Using PC12 cells exposed to clozapine,
      olanzapine, risperidone, quetiapine, ziprasidone, aripiprazole, and haloperidol,
      we measured intracellular ATP and mRNA and protein expression of enzymes and
      related substances involved in fatty acid synthesis and K(ATP) channel function.
      Forty-eight-hour treatment of cells with 50 MUM aripiprazole in 5.6 mM glucose
      decreased intracellular ATP. Only 50 MUM aripiprazole phosphorylated AMP
      activated protein kinase (AMPK); none of the other antipsychotics did so to a
      detectable level. Expression of carnitine palmitoyltransferase 1a, uncoupling
      protein 2, and sulfonylurea receptor 1 was unaffected by the antipsychotics,
      although expression of their mRNA was affected by AAPs. Pyrilamine (H(1) receptor
      antagonist), ketanserin (5HT(2) receptor antagonist), and raclopride (D(2)
      receptor antagonist) alone or in combination had no effect on expression of the
      aforementioned proteins. Therefore, although this study did not differentiate
      orexigenic and non-orexigenic AAPs, it suggests that aripiprazole is unique in
      its ability to activate AMPK.

PMID- 20686906
TI  - Chronic administration of harmine elicits antidepressant-like effects and
      increases BDNF levels in rat hippocampus.
AB  - A growing body of evidence has pointed to the beta-carboline harmine as a
      potential therapeutic target for the treatment of major depression. The present
      study was aimed to evaluate behavioural and molecular effects of the chronic
      treatment with harmine and imipramine in rats. To this aim, rats were treated for
      14 days once a day with harmine (5, 10 and 15 mg/kg) and imipramine (10, 20 and
      30 mg/kg) and then subjected to the forced swimming and open-field tests. Harmine
      and imipramine, at all doses tested, reduced immobility time of rats compared
      with the saline group. Imipramine increased the swimming time at 20 and 30 mg/kg
      and harmine increased swimming time at all doses. The climbing time increased in
      rats treated with imipramine (10 and 30 mg/kg) and harmine (5 and 10 mg/kg),
      without affecting spontaneous locomotor activity. Brain-derived neurotrophic
      factor (BDNF) hippocampal levels were assessed in imipramine and harmine-treated
      rats by ELISA sandwich assay. Interestingly, chronic administration of harmine at
      the higher doses (10 and 15 mg/kg), but not imipramine, increased BDNF protein
      levels in rat hippocampus. Finally, these findings further support the hypothesis
      that harmine could bring about behavior and molecular effects, similar to
      antidepressants drugs.

PMID- 20686907
TI  - Chronic variable stress induces oxidative stress and decreases
      butyrylcholinesterase activity in blood of rats.
AB  - Depressive disorders, including major depression, are serious and disabling,
      whose mechanisms are not clearly understood. Since life stressors contribute in
      some fashion to depression, chronic variable stress (CVS) has been used as an
      animal model of depression. In the present study we evaluated some parameters of
      oxidative stress [thiobarbituric acid reactive substances (TBARS), catalase
      (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx)], and
      inflammatory markers (interleukin 6, C reactive protein, tumor necrosis factor
      alpha and nitrites), as well as the activity of butyrylcholinesterase in blood of
      rats subjected to chronic stress. Homocysteine and folate levels also were
      measured. Stressed animals were submitted to different mild stressors for 40
      days. After CVS, a reduction in weight gain was observed in the stressed group,
      as well as an increase in immobility time in the forced swimming test as compared
      with controls. Stressed animals presented a significant increase on TBARS and
      SOD/CAT ratio, but stress did not alter GPx activity and any inflammatory
      parameters studied. CVS caused a significant inhibition on serum
      butyrylcholinesterase activity. Stressed rats had higher plasmatic levels of
      homocysteine without differences in folate levels. Although it is difficult to
      extrapolate our findings to the human condition, the alterations observed in this
      work may be useful to help to understand, at least in part, the pathophysiology
      of depressive disorders.

PMID- 20686909
TI  - Molecular dynamics simulation of drug uptake by polymer.
AB  - Drug uptake by polymer was modeled using a molecular dynamics (MD) simulation
      technique. Three drugs--doxorubicin (water soluble), silymarin (sparingly water
      soluble) and gliclazide (water insoluble)--and six polymers with varied
      functional groups--alginic acid, sodium alginate, chitosan, Gantrez AN119 (methyl
      vinyl-ether-co-malic acid based), Eudragit L100 and Eudragit RSPO (both acrylic
      acid based)--were selected for the study. The structures were modeled and
      minimized using molecular mechanics force field (MM+). MD simulation (Gromacs
      forcefield, 300 ps, 300 K) of the drug in the vicinity of the polymer molecule in
      the presence of water molecules was performed, and the interaction energy (IE)
      between them was calculated. This energy was evaluated with respect to electric
      dipole, van der Waals and hydrogen bond forces. A good linear correlation was
      observed between IE and our own previous data on drug uptake(*) [R2 = 0.65, R2adj
      = 0:65; R2pre = 0:56 and a F ratio of 30.25, P < 0.001; Devarajan et al. (2005) J
      Biomed Nanotechnol 1:1-9]. Maximum drug uptake by the polymeric nanoparticles
      (NP) was achieved in water as the solvent environment. Hydrophilic interaction
      between NP and water was inversely correlated with drug uptake. The MD simulation
      method provides a reasonable approximation of drug uptake that will be useful in
      developing polymer-based drug delivery systems.

PMID- 20686908
TI  - Docking and 3D-QSAR modeling of cyclin-dependent kinase 5/p25 inhibitors.
AB  - Structure-based 3D-QSAR approaches (CoMFA and CoMSIA) were applied to understand
      the structural requirements of the Cyclin-dependent kinase 5/p25 inhibitors.
      Cyclin-dependent kinase 5 (CDK5) is believed to play an important role in the
      development of the central nervous system during the process of mammalian
      embryogenesis. Genetic algorithm based docking program (GOLD) was successfully
      utilized to orient the compounds inside the binding pocket of the CDK5/p25
      structure. The adapted alignment method with the suitable parameters resulted in
      a reliable model. Furthermore, the final model was robust enough to forecast the
      activities of test compounds, satisfactorily. The contour maps were produced
      around the functional groups to understand the SAR requirements. Moreover, we
      also investigate the structural attributes of the inhibitors which make them
      selective toward CDK5/p25 over its close counterpart, i.e., CDK2. The study could
      be helpful to rationalize the new compounds with better inhibition and
      selectivity profiles against CDK5/p25.

PMID- 20686910
TI  - Metastatic collecting duct carcinoma of the kidney responded to sunitinib.
AB  - Collecting duct carcinoma (CDC) of the kidney is a rare and aggressive malignant
      tumor arising from the distal collecting tubules which has been shown to have a
      poor response to several kinds of systemic therapy. We present a case of
      metastatic CDC that responded favorably to a multiple tyrosine kinase inhibitor,
      sunitinib, achieving a partial response in both lung and skeletal metastases. To
      our knowledge, this is the first report showing therapeutic activity of sunitinib
      against CDC. Considering these findings, it would be worthwhile prospectively
      investigating the role of multiple tyrosine kinase inhibitors, particularly
      sunitinib, in the management of metastatic CDC.

PMID- 20686911
TI  - Successful long-term [corrected] remission following repeated salvage surgery in
      a patient with chemotherapy-resistant metastatic non-seminomatous [corrected]
      germ cell tumor: an additional report to Int J Clin Oncol 2007; 12:485-487.

PMID- 20686913
TI  - Symbiotic Streptomyces sp. TN119 GH 11 xylanase: a new pH-stable, protease- and
      SDS-resistant xylanase.
AB  - A pH-stable and protease-resistant xylanase (XynB119) was identified from
      Streptomyces sp. TN119, a strain isolated from the gut luminal contents of
      longhorned beetle (Batocera horsfieldi) larvae. Using the GC TAIL-PCR method, the
      1,026-bp coding gene (xynB119) with 67.3% GC content was successfully cloned and
      expressed in Escherichia coli. It encodes a 341-residue polypeptide with a
      calculated molecular mass of 35.9 kDa, including a putative 41-residue signal
      peptide, a catalytic domain of glycosyl hydrolase (GH) family 11, a short Gly/Pro
      rich linker, and a family 2 cellulose-binding domain (CBM 2). The deduced amino
      acid sequence is most similar to (61.9% identity) an endo-1,4-beta-xylanase from
      Streptomyces thermoviolaceus OPC-520. Purified recombinant XynB119 exhibited peak
      activity at 50  degrees C and pH 7.0, remained stable over a broad pH range
      (retaining >70% activity after incubation at pH 1.0-11.0 for 1 h at 37  degrees C
      without substrate), had strong protease resistance (retaining >90% activity after
      proteolytic treatment at 37  degrees C for 1 h) and SDS resistance (at 100 mM).
      These properties make XynB119 promising for application in the feed industry and
      valuable for basic research. Compared to r-XynB119, the r-XynB119 derivative
      without CBM 2 and linker region (r-XynB119d) exhibited a decreased pH stability
      of >25% at extreme pHs (pH 1.0-3.0 and pH 11.0-12.0).

PMID- 20686914
TI  - Isolation and characterization of alkalotolerant Pseudomonas sp. strain ISTDF1
      for degradation of dibenzofuran.
AB  - An alkalotolerant Pseudomonas strain was enriched and isolated from effluent of
      the pulp and paper industry. This strain was able to degrade dibenzofuran and
      utilize it as a sole source of energy and carbon. The GC-MS based detection of
      various intermediary metabolites of biodegradation suggested the involvement of
      angular as well as lateral pathway of dibenzofuran biodegradation. The GC-MS
      based detection of various intermediary metabolites of biodegradation suggested
      the involvement of angular as well as lateral pathway of dibenzofuran
      biodegradation. This diverse dioxygenation property of the strain allowed it to
      utilize various recalcitrant chlorinated xenobiotics and PAHs compounds. This
      strain showed optimum utilization (~85%) of dibenzofuran (200 mg l-1) within 36 h
      at pH 10 at 40  degrees C. The growth of the strain was supported by a wide range
      of environmental conditions such as temperature, pH, and concentration of
      dibenzofuran, suggesting that it can be used for in situ bioremediation of dioxin
      like compound.

PMID- 20686912
TI  - Proteases in cutaneous malignant melanoma: relevance as biomarker and therapeutic
      target.
AB  - Cutaneous malignant melanoma is the most aggressive skin cancer. It is also the
      most rapidly spreading cancer in terms of worldwide incidence. Although it is
      detected by simple inspection and can be relatively easily removed or treated,
      differential diagnosis to other melanocytic lesions, lack of prognostic markers,
      and no efficient treatment of advanced melanoma pose problems. Detection and
      targeting of proteases may represent a useful tool since they play a role in
      tumor cell metabolism, invasion, angiogenesis and metastasis. This review gives
      an overview of the role of proteases in development and progression of cutaneous
      malignant melanoma. In addition, regulation, activation, and interaction of
      proteases and their inhibitors are explained for tumors in general. The potential
      use of proteases as differential markers for melanoma mimicking melanocytic
      lesions, as biomarkers in tissues, and as prognostic serum markers is discussed.
      Current and future possibilities to target tumor proteases in therapy are
      presented.

PMID- 20686915
TI  - Genetic and biochemical characterization of a protease-resistant mesophilic beta
      mannanase from Streptomyces sp. S27.
AB  - A beta-mannanase gene, designated as man5S27, was cloned from Streptomyces sp.
      S27 using the colony polymerase chain reaction (PCR) method and expressed in
      Escherichia coli BL21 (DE3). The open reading frame consisted of 1,161 bp and
      encoded a 386-amino-acid polypeptide (Man5S27) with calculated molecular mass of
      37.2 kDa. The encoded protein comprised a putative 38-residue signal peptide, a
      family 5 glycoside hydrolase domain, and a family 10 carbohydrate-binding module.
      Purified recombinant Man5S27 had high specific activity of 2,107 U mg-1 and
      showed optimal activity at pH 7.0 and 65  degrees C. The enzyme remained stable
      at pH 5.0-9.0 and had good thermostability at 50 degrees C. The K (m) values for
      locust bean gum and konjac flour were 0.16 and 0.41 mg ml-1, with V(max) values
      of 3,739 and 1,653 MUmol min-1 mg-1, respectively. Divalent metal ions such as
      Mn2+, Zn2+, Ca2+, Pb2+, and Fe2+ enhanced the enzyme activity, but Ag+ and Hg2+
      strongly inhibited the activity. Man5S27 also showed resistance to various
      neutral proteases (retaining >95% activity after proteolytic treatment for 2 h).

PMID- 20686916
TI  - Sensitivity of laser flare photometry compared to slit-lamp cell evaluation in
      monitoring anterior chamber inflammation in uveitis.
AB  - To study the sensitivity of laser flare photometry (LFP) in monitoring anterior
      chamber inflammation by correlating LFP measurements with slit-lamp evaluation of
      aqueous cells in HLA-B27-related uveitis in a prospective trial. Slit-lamp cell
      evaluation was correlated with LFP-measured flare in a masked fashion in HLA-B27
      related uveitis patients receiving standard topical therapy. At the time of 50
      and 90% LFP flare reduction, the corresponding reduction of cells was recorded
      and statistically compared using the sign test. Forty-three episodes (in 43
      patients) of acute anterior HLA-B27-related uveitis were included. LFP flare
      reduction and slit-lamp cell reduction were strongly correlated. LFP was
      significantly more sensitive for both 50% (P = 0.001) and 90% (P = 0.02) LFP
      flare reduction in assessing the decrease of anterior chamber inflammation. LFP
      was superior to slit-lamp cell evaluation in monitoring anterior chamber
      inflammation in uveitis. Flare, becoming a quantitative parameter when measured
      by LFP, rather than cells, should be considered the gold standard to measure
      anterior chamber inflammation in uveitis.

PMID- 20686917
TI  - Neuroprotective role of lipoic acid against acute toxicity of N-acetylaspartic
      acid.
AB  - N-Acetylaspartic acid (NAA) accumulates in Canavan disease, a severe inherited
      neurometabolic disorder clinically characterized by mental retardation,
      hypotonia, macrocephaly, and seizures. The mechanisms of brain damage in this
      disease remain poorly understood. Recent studies developed by our research group
      showed that NAA induces oxidative stress in vitro and in vivo in cerebral cortex
      of rats. Lipoic acid is considered as an efficient antioxidant which can easily
      cross the blood-brain barrier. Considering the absence of specific treatment to
      Canavan disease, this study evaluates the possible prevention of the oxidative
      stress promoted by NAA in vivo by the antioxidant lipoic acid to preliminarily
      evaluate lipoic acid efficacy against pro-oxidative effects of NAA. Fourteen-day
      old Wistar rats received an acute administration of 0.6 mmol NAA/g body weight
      with or without lipoic acid (40 mg/kg body weight). Catalase (CAT), glutathione
      peroxidase (GPx), and glucose 6-phosphate dehydrogenase activities, hydrogen
      peroxide content, thiobarbituric acid-reactive substances (TBA-RS), spontaneous
      chemiluminescence, protein carbonyl content, total antioxidant potential, and DNA
      protein cross-links were assayed in the cerebral cortex of rats. CAT, GPx
      activities, and total antioxidant potential were significantly reduced, while
      hydrogen peroxide content, TBA-RS, spontaneous chemiluminescence, and protein
      carbonyl content were significantly enhanced by acute administration of NAA.
      Those effects were all prevented by lipoic acid pretreatment. Our results clearly
      show that lipoic acid may protect against the oxidative stress promoted by NAA.
      This could represent a new therapeutic approach to the patients affected by
      Canavan disease.

PMID- 20686918
TI  - Identification and characterization of uncoupling protein in heart and muscle
      mitochondria of canary birds.
AB  - An uncoupling protein (cUCP) was identified in heart and skeletal muscle
      mitochondria of canary birds. cUCP was immunodetected using polyclonal antibodies
      raised against murine UCP2. Its molecular mass was similar to those of mammalian
      UCPs (32 kDa). The activity of cUCP was stimulated by palmitic acid (PA) and
      inhibited by GTP mainly in state 3 respiration. Additions of PA augmented state 4
      respiration and lowered the ADP/O ratio. Thus, the activity of cUCP diverted
      energy from oxidative phosphorylation in state 3 respiration. cUCP in heart and
      skeletal muscles of canary birds might have implications in thermogenesis as well
      as protection against free radical production.

PMID- 20686919
TI  - The effects of different laser pulse lengths on the embryo biopsy procedure and
      embryo development to the blastocyst stage.
AB  - PURPOSE: a laser is commonly used to remove a blastomere from an embryo for
      genetic testing. The laser uses intense heat which could possibly disrupt embryo
      development. It is the goal of this study to test the effects of different laser
      pulse lengths (and consequently heat) on the embryo biopsy procedure and embryo
      development. METHODS: each embryo biopsy was performed randomly utilizing laser
      pulse lengths of 0.604mS (group I), 0.708mS (group II), and 1.010mS (group III).
      RESULTS: for groups I, II, and III, 83, 86, and 71 embryos were biopsied,
      respectively. There was no difference in day 5 embryo quality or lysed
      blastomeres between groups. Average number of blastomeres biopsied between group
      I (1.0 +/- 0.0), II (1.0 +/- 0.2), and III (1.1 +/- 0.2) was significant
      (0.0001). CONCLUSION: our data demonstrates that laser pulse length does not
      influence the embryo biopsy procedure or embryo development.

PMID- 20686920
TI  - Linking behavioural alterations with biomarkers responses in the European seabass
      Dicentrarchus labrax L. exposed to the organophosphate pesticide fenitrothion.
AB  - The acute effects of the organophosphate insecticide fenitrothion on
      Dicentrarchus labrax juveniles were investigated through a bioassay using
      biomarkers and swimming behaviour as effect criteria. After 96 h of exposure to
      sub-lethal concentrations of fenitrothion, the swimming velocity and several
      biomarkers were individually determined, namely: brain acetylcholinesterase
      (AChE) activity; muscle cholinesterases (ChE), lactate dehydrogenase and
      isocitrate dehydrogenase activities; liver ethoxyresorufin-O-deethylase (EROD),
      glutathione S-transferases, glutathione peroxidase, glutathione reductase,
      catalase and superoxide dismutase (SOD) activities and lipid peroxidation levels
      (LPO). A significant decrease of the swimming velocity (LOEC = 2 mg l(-1)), an
      inhibition of both AChE (LOEC = 0.06 mg l(-1)) and ChE activities (LOEC = 0.03 mg
      l(-1)), and a positive and significant correlation between the swimming velocity
      and AChE were found in exposed fish, suggesting an influence of the inhibition of
      these enzymes in the swimming velocity decrease. An increase of EROD activity
      (LOEC = 1 mg l(-1)), indicating the involvement of this enzyme in fenitrothion
      biotransformation, and a negative and significant correlation between EROD
      activity and swimming velocity were also found, suggesting that the two findings
      may somehow be related. Furthermore, results show a significant induction of SOD
      (LOEC = 0.13 mg l(-1)) without LPO increase, suggesting that the enzyme is
      preventing oxidative stress damage. No significant alterations were found in any
      of the other parameters tested. Thus, exposure of seabass to fenitrothion in the
      wild at concentrations similar to those tested here may have adverse consequences
      at population level as neurotransmission and swimming ability are essential for
      fish performance and survival.

PMID- 20686921
TI  - Examining the psychological sense of community for individuals with serious
      mental illness residing in supported housing environments.
AB  - The psychological sense of community is an important aspect of community life;
      yet, it remains largely unexamined among individuals with serious mental illness
      (SMI). Sense of community represents the strength of bonding among community
      members; and this social phenomenon likely impacts the process by which
      individuals with SMI integrate into community life. The current study examined
      sense of community (SOC) for individuals with SMI by assessing the relationships
      between neighborhood experiences, unique factors related to SMI (e.g., mental
      illness diagnosis), and sense of community in the neighborhood. Participants were
      402 residents of supported housing programs who used mental health services in
      South Carolina. Hierarchical linear regression was utilized to determine which
      components of community life helped to explain variability in sense of community.
      In total, 214 participants reported that it is very important for them to feel a
      sense of community in their neighborhoods. Neighbor relations, neighborhood
      safety, neighborhood satisfaction, neighborhood tolerance for mental illness, and
      housing site type emerged as significant explanatory variables of sense of
      community. These findings have implications for interventions aimed at enhancing
      SOC and community integration for individuals with SMI.

PMID- 20686922
TI  - Simultaneous measurement of anisotropic solute diffusivity and binding reaction
      rates in biological tissues by FRAP.
AB  - Several solutes (e.g., growth factors, cationic solutes, etc.) can reversibly
      bind to the extracellular matrix (ECM) of biological tissues. Binding
      interactions have significant implications on transport of such solutes through
      the ECM. In order to fully delineate transport phenomena in biological tissues,
      knowledge of binding kinetics is crucial. In this study, a new method for the
      simultaneous determination of solute anisotropic diffusivity and binding reaction
      rates was presented. The new technique was solely based on Fourier analysis of
      fluorescence recovery after photobleaching (FRAP) images. Computer-simulated FRAP
      tests were used to assess the sensitivity and the robustness of the method to
      experimental parameters, such as anisotropic solute diffusivity and rates of
      binding reaction. The new method was applied to the determination of diffusivity
      and binding rates of 5-dodecanoylaminofluorescein (DAF) in bovine coccygeal
      annulus fibrosus (AF). Our findings indicate that DAF reversibly binds to the ECM
      of AF. In addition, it was found that DAF diffusion in AF is anisotropic. The
      results were in agreement with those reported in previous studies. This study
      provides a new tool for the simultaneous determination of solute anisotropic
      diffusion tensor and rates of binding reaction that can be used to investigate
      diffusive-reactive transport in biological tissues and tissue engineered
      constructs.

PMID- 20686923
TI  - Characterizing the dynamics of postural sway in humans using smoothness and
      regularity measures.
AB  - We investigate human postural sway velocity time series by computing two
      dynamical statistics quantifying the smoothness (the central tendency measure or
      CTM) and the regularity (the sample entropy or SampEn) of their underlying
      dynamics. The purpose of the study is to investigate the effect of aging and
      vision on the selected measures and to explore the nature of postural dynamics by
      performing surrogate data tests. A group of 14 young subjects was compared to a
      group of 11 older healthy subjects in two visual conditions: with eyes open (EO)
      and with eyes closed (EC). The results suggest that vision and age do not
      influence the two statistics of the velocity data in the same way. More
      specifically, the smoothness statistic is able to detect the aging effect. The
      regularity measure is sensitive to the visual feedback removal. In contrast with
      some findings in the literature, the results of the surrogate data tests indicate
      that the center of pressure velocity dynamics are stochastic and are not produced
      by a purely deterministic behavior. Finally, we discuss some potential
      implications of our results in terms of postural control mechanisms.

PMID- 20686924
TI  - Health-related quality of life of Iranian children with attention
      deficit/hyperactivity disorder.
AB  - BACKGROUND: The present study aimed to examine the psychometric properties of the
      Persian version of the 23-item PedsQLTM 4.0 Generic Core Scales in Iranian
      children with attention deficit hyperactivity disorder (ADHD). METHODS: A
      clinical sample of seventy-two children aged 8-17 years with ADHD and their
      parents completed the questionnaire. The control group consisted of 140 children
      matched for age and gender selected from schools by cluster sampling method. The
      English language version of the PedsQLTM 4.0 was translated into Persian. Factor
      analysis was conducted. RESULTS: Reliability analysis for the total scale score
      was 0.85 for the child report and it was 0.80 for parent report version. Factor
      loading for items of the questionnaire was very similar to its original version.
      The quality of life of children with ADHD was statistically lower than that of
      the control group. CONCLUSION: The Persian version of the scales has adequate
      reliability and validity. The HRQOL of children with ADHD is lower than that of
      the control group. It is lower than that of the community sample of ADHD children
      from USA or children with cancer.

PMID- 20686925
TI  - Development of sense of coherence in adulthood: a person-centered approach. The
      population-based HeSSup cohort study.
AB  - OBJECTIVE: We sought to identify the most typical patterns of change in sense of
      coherence (SOC) in adulthood. METHODS: This prospective population-based Health
      and Social Support (HeSSup) study was based on four age cohorts including men and
      women initially aged 20-24 years (n = 4,682), 30-34 years (n = 4,248), 40-44
      years (n = 4,598), and 50-54 years (n = 4,997). SOC was assessed at baseline and
      at the 5-year follow-up point. Factor Mixture Modeling was used to identify the
      latent classes of persons whose mean changes in SOC were similar over time.
      RESULTS: Three development classes were supported by the data. In all age
      cohorts, the largest class consisted of those people whose SOC was high at
      baseline and increased thereafter (46-58% of participants depending on the age
      group). A class of high SOC with a decreasing trend and that of low SOC with an
      increasing trend were also found. In all age groups, the rank-order stability was
      high in the first development class (0.84-0.98) but low in other classes (0.35
      0.44). CONCLUSION: This analysis shows continuous increase in the level of SOC
      over time to be common in adulthood, irrespective of age. High SOC, rather than
      higher age, seems to determine a stable development of the SOC.

PMID- 20686926
TI  - Racemisation and human cataract. D-Ser, D-Asp/Asn and D-Thr are higher in the
      lifelong proteins of cataract lenses than in age-matched normal lenses.
AB  - ASTRACT: Several amino acids were found to undergo progressive age-dependent
      racemisation in the lifelong proteins of normal human lenses. The two most highly
      racemised were Ser and Asx. By age 70, 4.5% of all Ser residues had been
      racemised, along with >9% of Asx residues. Such a high level of inversion,
      equivalent to between 2 and 3 D- amino acids per polypeptide chain, is likely to
      induce significant denaturation of the crystallins in aged lenses. Thr, Glx and
      Phe underwent age-dependent racemisation to a smaller degree. In model
      experiments, D- amino acid content could be increased simply by exposing intact
      lenses to elevated temperature. In cataract lenses, the extent of racemisation of
      Ser, Asx and Thr residues was significantly greater than for age-matched normal
      lenses. This was true, even for cataract lenses removed from patients at the
      earliest ages where age-related cataract is observed clinically. Racemisation of
      amino acids in crystallins may arise due to prolonged exposure of these proteins
      to ocular temperatures and increased levels of racemisation may play a
      significant role in the opacification of human lenses.

PMID- 20686927
TI  - Automatic breast parenchymal density classification integrated into a CADe
      system.
AB  - PURPOSE: Breast parenchymal density is an important risk factor for breast
      cancer. It is known that mammogram interpretation is more difficult where dense
      tissue is involved. Therefore, automated breast density classification may aid in
      breast lesion detection and analysis. METHODS: Several image pattern
      classification techniques for screen-film (SFM) mammography datasets were tested
      and classified according to BIRADS categories using known cases. A hierarchical
      classification procedure based on k-NN, SVM and LBN combined with principal
      component analysis on texture features uses the breast density features. The
      classification techniques have been incorporated into a CADe system to drive the
      detection algorithms. RESULTS: The results obtained on 322 mammograms demonstrate
      that up to 84% of samples were correctly classified. The results of the lesion
      detection algorithms were obtained from modules integrated within the CADe system
      developed by the authors. CONCLUSIONS: The ability to detect suspicious lesions
      on dense and heterogeneous tissue has been tested. The tools enhance the
      detectability of lesions and they are able to distinguish their local attenuation
      without local tissue density constraints.

PMID- 20686928
TI  - Expression profile in omental and subcutaneous adipose tissue from lean and obese
      subjects. Repression of lipolytic and lipogenic genes.
AB  - The adipose tissue is a highly regulated endocrine and paracrine organ that
      secretes a wide variety of biologically active molecules involved in the control
      of energy balance and the regulation of body weight. Our work aimed to analyze
      the dysregulation of the adipocyte metabolism and compare the gene expression
      patterns between omental (OM) and subcutaneous (SC) adipose tissue from obese and
      lean subjects by using whole-genome DNA microarrays. OM and SC adipose tissues
      were obtained from 43 obese subjects undergoing bariatric surgery and from six
      lean individuals. Gene expression analysis was performed by whole-genome
      microarrays and Taqman RT-PCR. The analysis of microarrays showed upregulation of
      545 genes in OM and 47 in SC adipose tissue, whereas 723 and 27 genes were
      downregulated in OM and SC tissue, respectively, in obese patients. Significantly
      altered genes showed at least a twofold change of p < 0.05. Validation of the
      arrays with 28 genes was carried out by using low density microfluidic cards
      which confirmed the changes found in most genes. We focused on the altered
      expression of gene coding for enzymes and transcription factors involved in lipid
      metabolism. Interestingly, some of these genes have not been previously described
      in obesity. Our results show that adipose tissue from obese subjects entails
      defense mechanisms against an excessive expansion and fat accumulation,
      repressing both lipogenesis and lipolysis.

PMID- 20686929
TI  - Initial experience with robotic sleeve gastrectomy for morbid obesity.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is used with increasing
      frequency for the treatment of morbid obesity. The application of robotic
      techniques has been reported for bariatric operations like laparoscopic Roux-en-Y
      gastric bypass and laparoscopic adjustable gastric banding, but not for LSG. We
      report herein our initial experience with LSG performed with the use of the Da
      Vinci surgical system. METHODS: Nineteen consecutive patients underwent LSG with
      the use of the Da Vinci surgical system by the same surgical team. Surgical
      techniques followed the principles of standard LSG. Preparation of the stomach
      was performed by the console surgeon and its division with the staplers by the
      patient-side surgeon. RESULTS: Seventeen women and two men with a mean age of
      39.4 years and a mean body mass index (BMI) of 48.2 kg/m(2) were operated. Mean
      operative time was 95.5 +/- 11.5 min. Docking time was 16 +/- 4.2 min. There were
      no conversions. Peri-operative morbidity and mortality was zero. Time to BMI
      ratio for robotic LSG was 2 +/- 0.3 min/kg/m(2) and it was equal to the
      respective of our standard LSGs. When the docking time was excluded, the same
      ratio was 1.7 +/- 0.2, significantly shorter than the respective 2.0 +/- 0.5 of
      our conventional LSGs (p = 0.018). Mean excess body weight loss 1 year post
      operatively was 65.5 +/- 25.6%. CONCLUSIONS: Robotic laparoscopic sleeve
      gastrectomy is a feasible, safe, and efficient surgical technique for the
      treatment of morbid obesity and it does not add to the operating time of the
      procedure.

PMID- 20686930
TI  - Is the presence of microalbuminuria a relevant marker of kidney disease?
AB  - Levels of urinary albumin excretion that are below the usual limit of detection
      by qualitative testing, but are above normal levels (microalbuminuria; MA), can
      be readily identified by simple measures, such as the urinary albumin to
      creatinine ratio in untimed urine samples. Such measurements, particularly when
      combined with assessment of estimated glomerular filtration rate (eGFR), have
      utility as biomarkers for enhanced risk of all-cause mortality, cardiovascular
      events, progressive chronic kidney disease, and end-stage renal disease in
      diabetic and nondiabetic subjects. However, it is controversial whether
      "isolated" MA (MA in the absence of a clear reduction in eGFR, urine sediment
      abnormalities, or structural renal disease) should be regarded as kidney disease.
      Such MA could also be regarded as a manifestation of a diffuse endothelial
      (microvascular) injury and thereby collateral kidney damage. This article reviews
      the current evidence concerning MA as a marker of kidney disease or kidney
      damage.

PMID- 20686931
TI  - Are preservice teachers prepared to teach struggling readers?
AB  - Reading disabilities such as dyslexia, a specific learning disability that
      affects an individual's ability to process written language, are estimated to
      affect 15-20% of the general population. Consequently, elementary school teachers
      encounter students who struggle with inaccurate or slow reading, poor spelling,
      poor writing, and other language processing difficulties. However, recent
      evidence may suggest that teacher preparation programs are not providing
      preservice teachers with information about basic language constructs and other
      components related to scientifically based reading instruction. As a consequence
      preservice teachers have not exhibited explicit knowledge of such concepts in
      previous studies. Few studies have sought to assess preservice teachers'
      knowledge about dyslexia in conjunction with knowledge of basic language
      concepts. The purpose of the present study was to examine elementary school
      preservice teachers' knowledge of basic language constructs and their perceptions
      and knowledge about dyslexia. Findings from the present study suggest that
      preservice teachers, on average, are able to display implicit skills related to
      certain basic language constructs (i.e., syllable counting), but fail to
      demonstrate explicit knowledge of others (i.e., phonics principles). Also,
      preservice teachers seem to hold the common misconception that dyslexia is a
      visual perception deficit rather than a problem with phonological processing.
      Implications for future research as well as teacher preparation are discussed.

PMID- 20686932
TI  - In brief: Statistics in brief: study designs in orthopaedic clinical research.

PMID- 20686933
TI  - Management of intraoperative medial collateral ligament injury during TKA.
AB  - BACKGROUND: Intraoperative injuries to the medial collateral ligament are often
      unrecognized and failure to appropriately manage ligament loss may result in knee
      instability and loosening. QUESTIONS/PURPOSES: We compared the functional scores
      in patients with iatrogenic injury to the medial collateral ligament (MCL)
      treated with additional constraint to those without. METHODS: We retrospectively
      reviewed the records of all 1478 patients (1650 knees) who underwent primary TKA
      between 1998 and 2004. Thirty-seven patients (2.2%) had recognized intraoperative
      injury to the MCL; the remaining 1441 patients (1613 knees) served as controls.
      We attempted to repair the ligament in 14 patients; increased prosthetic
      constraint over that planned was used in 30 of the 37 patients. We determined
      Knee Society scores (KSS) in all patients. Three patients were lost to followup.
      The minimum followup was 36 months (average, 54 months; range, 36-120 months).
      RESULTS: The mean KSS for all MCL injury knees for pain and function averaged 81
      and 74 points, respectively, compared with 91 and 87 for the control group.
      However, in the 30 knees in which the MCL insufficiency was treated with
      increased constraint, the mean scores for pain and function increased to 88 and
      83 points, respectively. Four of the seven patients treated without increased
      prosthetic constraint were revised for instability; no revisions for instability
      were performed in the 37 patients treated with additional constraint.
      CONCLUSIONS: Recognition of MCL injury during TKA is crucial, since using
      nonstabilizing inserts was associated with residual instability requiring
      revision. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for
      Authors for a complete description of levels of evidence.

PMID- 20686935
TI  - Letter to the editor: pelvic fractures in women of childbearing age.

PMID- 20686936
TI  - 50 Years AGo in CORR: Dupuytren's contracture: a guide for management L. D.
      Howard MD CORR 1959;15:118-126.

PMID- 20686937
TI  - Parosteal osteogenic sarcoma: treatment by block resection. Everett J. Gordon MD
      CORR 1959;14:171-178.

PMID- 20686939
TI  - RNAi in stem cells: current status and future perspectives.
AB  - RNAi is a mechanism displayed by most eukaryotic cells to rid themselves of
      foreign double-strand RNA molecules. In the 11 years since the initial report,
      RNAi has now been demonstrated to function in mammalian cells to alter gene
      expression and used as a means for genetic discovery as well as a possible
      strategy for genetic correction and genetic therapy in cancer and other diseases.
      The aim of this review is to provide a general overview of how RNAi suppresses
      gene expression, examine some published RNAi approaches that have resulted in
      changes in stem cell function, and suggest the possible clinical relevance of
      this work in cancer therapy through targeting cancer stem cells.

PMID- 20686940
TI  - A brief introduction to RNAi and microRNAs in stem cells.
AB  - Recently, RNAi, including microRNAs (miRNAs), has become an important tool to
      investigate the regulatory mechanism of stem cell maintenance and
      differentiation. In this short chapter, we will give a brief overview of the
      discovery history, functions, and mechanisms of RNAi and miRNAs. We will also
      discuss RNAi as a tool to study stem cell function and the potential future
      practical applications.

PMID- 20686941
TI  - Forward RNAi screens in human stem cells.
AB  - Identifying the genes and pathways that regulate self-renewal and differentiation
      in somatic stem cells is a central goal in stem cell and cancer biology. Here, we
      describe a method for RNAi-based screens in primary human hematopoietic stem and
      progenitor cells. These cells are suitable targets for complex, selection-based
      screens using pooled lentiviral shRNA libraries. The screening approach is a
      promising new tool to dissect regulatory mechanisms in hematopoietic and somatic
      stem cells, in general, and may be particularly useful to identify gene targets
      and modifiers that can be further exploited in strategies for ex vivo stem cell
      expansion.

PMID- 20686942
TI  - A recessive genetic screen for components of the RNA interference pathway in
      mouse embryonic stem cells.
AB  - Several key components of the RNA interference (RNAi) pathway were identified in
      genetic screens performed in nonmammalian model organisms. To identify components
      of the mammalian RNAi pathway, we developed a recessive genetic screen in mouse
      embryonic stem (ES) cells. Recessive genetic screens are feasible in ES cells
      that are Bloom-syndrome protein (Blm-) deficient. Therefore, we constructed a
      reporter cell line in Blm-deficient ES cells to isolate RNAi mutants through a
      simple drug-selection scheme. This chapter describes how we used retroviral gene
      traps to mutagenize the reporter cell line and select for RNAi mutants. Putative
      RNAi mutants were confirmed using a separate functional assay. The location of
      the gene trap was then identified using molecular techniques such as Splinkerette
      PCR. Our screening strategy successfully isolated several mutant clones of
      Argonaute2, a vital component of the RNAi pathway.

PMID- 20686943
TI  - Construction and application of random dsRNA interference library for functional
      genetic screens in embryonic stem cells.
AB  - RNA interference (RNAi) libraries have been proven to be a powerful tool for
      large-scale functional genetic screens. To facilitate high-throughput functional
      genetic screens in embryonic stem cells, a system for construction of random
      dsRNA expressing RNAi libraries was developed. Previous studies have demonstrated
      that sequence-specific gene silencing could be induced by long dsRNA in mouse
      embryos, mouse oocytes, embryonic stem cells, and some other mammalian cells. Our
      study demonstrated that the dsRNA interference library can be used for functional
      genetic screens of genes involved in self-renewal of embryonic stem cells (ES
      cells). The random RNAi library is easy to construct and provides a useful tool
      for investigation of molecular mechanisms of cellular development and
      differentiation.

PMID- 20686944
TI  - Establishing efficient siRNA knockdown in stem cells using fluorescent
      oligonucleotides.
AB  - The following protocols provide a rapid approach for establishing good working
      conditions for transfecting siRNAs for specific gene knockdown. By first using
      microscopy to evaluate efficient transfection of an inexpensive, fluorescent
      oligonucleotide, the researcher can later proceed with more expensive Western
      blot or quantitative real-time PCR (qRT-PCR) methods. Thus, the main culprit of
      ineffective knockdown, poor transfection, can be eliminated before engaging in
      tedious and time-consuming approaches for troubleshooting siRNA knockdown
      experiments.

PMID- 20686945
TI  - Loss-of-function studies in mouse embryonic stem cells using the pHYPER shRNA
      plasmid vector.
AB  - RNA interference is widely used for loss-of-function studies in mammalian cells.
      As an alternative to the transfection of small RNAs, plasmid vectors have been
      developed to express short hairpin RNAs (shRNAs). We engineered the pHYPER shRNA
      vector, which is based on a 2.5-kb mouse genomic fragment encompassing the H1
      gene. We have previously shown that this shRNA vector is highly efficient for
      both transient transfection studies in embryonic stem (ES) cells and generation
      of stable ES cell lines. Following ES cell transfection, the H1 promoter of
      pHYPER is recognized by the RNA polymerase III machinery, which directs the
      transcription of the shRNA. We provide here detailed protocols that explain how
      to optimize the use of pHYPER in ES cells.

PMID- 20686946
TI  - Regulation and/or repression of cholinergic differentiation of murine embryonic
      stem cells using RNAi directed against transcription factor L3/Lhx8.
AB  - Techniques for controlling the expression of a specific gene in embryonic stem
      cells are effective and important for clarifying the functions of the gene.
      Regarding differentiation of cells into nervous system components, these
      techniques would play key roles in elucidating, not only the differentiation
      mechanisms of neuronal and glial cells, but also how neuronal phenotypes are
      determined. In this chapter, we describe an RNA interference method for
      suppressing cholinergic differentiation in murine embryonic stem cells by
      knockdown of expression of the transcription factor L3/Lhx8, a Lim homeobox gene
      family protein. This method will greatly facilitate functional analyses of the
      factors involved in neuronal differentiation and regeneration and contribute to
      cell transplantation studies.

PMID- 20686947
TI  - Silencing of Rho-GDIgamma by RNAi promotes the differentiation of neural stem
      cells.
AB  - RNA interference (RNAi) technology is one of the main means in the study of stem
      cell differentiation. This study describes Rho-GDIgamma function during the
      differentiation of neural stem cells by using RNAi. Rho-GDIgamma belongs to the
      Rho-GDI protein family, which is expressed at high level throughout the brain.
      Although it exists in neuronal population, its physiological function is poorly
      understood. By using RNAi technology to downregulate expression of Rho-GDIgamma,
      we found distinct morphological changes in neural stem cell line C17.2. More
      important, RT-PCR confirmed that RNAi-mediated downregulation of Rho-GDIgamma
      decreased expression of Rho-GDIgamma-regulated genes RhoA and slightly increased
      expression of Rac1. Further, immunochemical staining indicated that
      downregulation of Rho-GDIgamma increased the tendency of C17.2 cells to
      differentiate. These data strongly suggest that Rho-GDIgamma plays a key role in
      the differentiation of neural stem cells.

PMID- 20686948
TI  - RNAi knockdown of redox signaling protein Ape1 in the differentiation of mouse
      embryonic stem cells.
AB  - Murine embryonic stem cells (ES) are pluripotent cells and have the potential to
      become a wide variety of specialized cell types. Mouse ES cell differentiation
      can be regarded as a valuable biological tool that has led to major advances in
      our understanding of cell and developmental biology. In vitro differentiation of
      mouse ES cells can be directed to a specific lineage formation, such as
      hematopoietic lineage, by appropriate cytokine and/or growth factor stimulation.
      To study specific gene function in early developmental events, gene knockout
      approaches have been traditionally used; however, this is a time-consuming and
      expensive approach. Recently, we have shown that siRNA is an effective strategy
      to knockdown target gene expression, such as Ape1, during ES cell
      differentiation, and consequently, one can alter cell fates in ES-derived
      differentiated cells. This approach will be applicable to test the function of a
      wide variety of gene products using the ES cell differentiation system.

PMID- 20686949
TI  - Proteins involved in cell migration from glioblastoma neurospheres analyzed by
      overexpression and siRNA-mediated knock-down.
AB  - Glioblastoma multiforme (GBM) are the most common malignant brain tumours in
      adults, characterized by short survival periods of patients. Their aggressive
      local growth pattern and increased invasiveness, due to a high motility of the
      tumour cells, hamper treatment. However, the molecular mechanisms regulating
      glioblastoma cell migration are still elusive. Here, we describe the combination
      of a highly efficient cell transfection by nucleofection technology and the
      generation of spheroids from these transfected glioblastoma cell lines.
      Nucleofection allows the manipulation of protein expression by overexpression and
      siRNA-mediated protein knock-down. Transfection efficiencies >80% can be achieved
      with some GBM cell lines. Transfected neurospheres then can be used for migration
      assays (as described here in detail) and a multitude of other functional assays.
      In comparison to monolayer cultures, the advantage of spheroids is their
      resemblance to organized tissue in combination with the accuracy of in vitro
      methodology and marked experimental flexibility.

PMID- 20686950
TI  - An efficient transfection method for mouse embryonic stem cells.
AB  - Embryonic stem (ES) cells are an important source of stem cells in tissue
      engineering and regenerative medicine because of their high self-renewal
      capacities and differentiation potentials. However, the detailed molecular
      mechanisms controlling the differentiation and renewal programs in ES cells
      remained unclear. One of the difficulties in understanding these mechanisms
      substantially results from the low efficacies of gene manipulation by delivering
      exogenous gene expression or knockdown of endogenous gene expression with small
      interfering RNA (siRNA) in ES cells. Here we describe an optimized protocol for
      efficiently transfecting mouse ES cells by Effectene, a liposome-based method.
      The high transfection efficiency in mouse ES cells is demonstrated in this
      chapter by (1) achieving a percentage of enhanced green fluorescence protein
      (EGFP) expression in >98% embryoid bodies after introducing plasmids encoding the
      protein and (2) decreased SOX-2 and Oct-3/4 expression and subsequent
      morphological evidence of cell differentiation after introducing siRNA expression
      for suppressing SOX-2 and Oct-3/4, which are known to be essential for
      maintenance of stem cell properties in mouse ES cells.

PMID- 20686951
TI  - Semi-quantitative analysis of transient single-cell gene expression in embryonic
      stem cells by femtoinjection.
AB  - Single-cell manipulation supporting robot (SMSR) has enabled femtoinjection, a
      high-throughput and semi-quantitative microinjection in the range of femtogram
      (fg) DNA and other molecules. An enhanced green fluorescent protein (EGFP) gene
      expression vector can be introduced directly into mouse embryonic stem cells at
      100 cells/h with a 10% success rate. The intensity of EGFP fluorescence in single
      ES cells or single colonies of ES cells increases as the concentration of an EGFP
      gene expression vector in the injection capillary increases from 1 to 50 ng/muL.
      On the other hand, the knockdown of EGFP gene expression can be demonstrated by
      femtoinjection of siRNA against EGFP or an shRNA expression vector using an EGFP
      expressing ES cell line. Femotoinjection can provide a useful method for
      quantitative analysis of transient gene expression in single cells using RNAi.

PMID- 20686952
TI  - Preparation and analysis of microRNA libraries using the Illumina massively
      parallel sequencing technology.
AB  - MicroRNAs are key regulators of gene expression in diverse biological processes
      and their importance in embryonic stem cells is indisputable. New 'next
      generation' technologies such as Illumina massively parallel sequencing offer
      vast improvements, in both scale and sensitivity, to microRNA profiling studies.
      We describe a detailed procedure for the preparation of small RNA libraries for
      Illumina sequencing. We further comment on approaches for analyzing the resultant
      sequence data for measuring microRNA abundance.

PMID- 20686953
TI  - Assessing in vivo microRNA function in the germline stem cells of the Drosophila
      ovary.
AB  - A more complete understanding of the biology of adult stem cells could yield
      important insights toward devising effective cell-based regenerative therapies to
      treat disease. The germline stem cells (GSCs) in the fruit fly Drosophila
      melanogaster are an excellent in vivo model for the study of adult stem cell
      biology. There is increasing evidence from a growing field that microRNAs
      (miRNAs) play important roles in controlling many aspects of stem-cell biology.
      Using straightforward genetic manipulations combined with well-established cell
      biological analysis techniques, we and others have found that the miRNA pathway
      regulates the cell division rate of Drosophila GSCs as well as the maintenance of
      the GSCs in their niche. In this chapter, we offer a detailed, self-contained
      description of a general method to assess the in vivo functions of miRNAs in the
      GSCs of the Drosophila ovary.

PMID- 20686954
TI  - Monitoring microRNA expression during embryonic stem-cell differentiation using
      quantitative real-time PCR (qRT-PCR).
AB  - Quantitative real-time PCR (qRT-PCR) is a reliable method to determine and
      monitor microRNA (miRNA) expression profiles in different cells, tissues, and
      organisms. Although there are several different strategies for performing qRT-PCR
      to determine miRNA expression, all of them have two steps in common: reverse
      transcription for obtaining cDNA from mature miRNA sequence and standard real
      time PCR for amplification of cDNA. This chapter demonstrates the application of
      TaqMan-based real-time PCR for determining miRNA expression profiles during mouse
      embryonic stem-cell differentiation. In this method, a mature miRNA sequence is
      first reverse transcribed into a long cDNA with a 40- to 50-nt miRNA-specific
      stem-loop primer; then, a standard real-time PCR reaction is performed for
      determining miRNA expression using a forward miRNA-specific primer, a universal
      reverse primer, and FAM dye-labeled TaqMan probes.

PMID- 20686955
TI  - Engineering human mesenchymal stem cells to release adenosine using miRNA
      technology.
AB  - Adenosine is an important modulator of metabolic activity with powerful tissue-
      and cell-protective functions. Adenosine kinase (ADK), the major adenosine
      regulating enzyme, is critical to adapt its intra- and extra-cellular levels in
      response to environmental changes. Lentiviral RNAi-mediated down-regulation of
      ADK in human mesenchymal stem cells (hMSCs) has therefore been considered an
      effective tool for engineering therapeutically effective adenosine-releasing cell
      grafts that could constitute patient-identical autologous implants for clinical
      application. We constructed lentiviral vectors that coexpress miRNA directed
      against ADK and an emerald green fluorescent protein (EmGFP) reporter gene.
      Following lentiviral transduction of hMSCs, we demonstrated up to 80% down
      regulation of ADK and 98% transduction efficiency. Transduced hMSCs continued to
      express EmGFP after 4-6 consecutive passages and EmGFP-positive hMSC grafts
      survived in the hippocampal fissure of mouse brains and provided efficient
      adenosine-dependent neuroprotection in a mouse model of seizure-induced cell
      loss.

PMID- 20686956
TI  - Efficient gene knockdowns in mouse embryonic stem cells using microRNA-based
      shRNAs.
AB  - RNA interference (RNAi) is a powerful gene-knockdown technology that has been
      applied for functional genetic loss-of-function studies in many model eukaryotic
      systems, including embryonic stem cells (ESCs). Application of RNAi in ESCs
      allows for dissection of mechanisms by which ESCs self-renew and maintain
      pluripotency, and also specifying particular cell types needed for cell
      replacement therapies. Potent RNAi response can be induced by expression of an
      microRNA-embedded short-hairpin RNA (shRNA(mir)) cassette that is integrated in
      the genome by virus infection or site-specific recombination at a defined locus.
      In this chapter, I will provide detailed protocols to perform shRNA(mir)-mediated
      RNAi studies in mouse ESCs using retrovirus infection and loxP site-directed
      recombination for efficient constitutive and inducible gene knockdown,
      respectively.

PMID- 20686957
TI  - Hypoxic tumors and their effect on immune cells and cancer therapy.
AB  - The abnormal decrease or the lack of oxygen supply to cells and tissues is called
      hypoxia. This condition is commonly seen in various diseases such as rheumatoid
      arthritis and atherosclerosis, also in solid cancers. Pre-clinical and clinical
      studies have shown that hypoxic cancers are extremely aggressive, resistant to
      standard therapies (chemotherapy and radiotherapy), and thus very difficult to
      eradicate. Hypoxia affects both the tumor and the immune cells via various
      pathways. This review summarizes the most common effects of hypoxia on immune
      cells that play a key role in the anti-tumor response, the limitation of current
      therapies, and the potential solutions that were developed for hypoxic
      malignancies.

PMID- 20686958
TI  - Characterization of regulatory T cells in tumor suppressive microenvironments.
AB  - Increasing evidence suggests that immunotherapy is a promising strategy for
      treating patients with invasive and metastatic cancers, but clinical trails are
      discouraging so far. Recent studies showed that several subsets of regulatory
      tumor-infiltrating lymphocytes (TILs), such as naturally occurring CD4(+)CD25(+)
      regulatory T cells (Treg), and adaptively induced Treg cells of Tr1, Th3, CD8(+),
      as well as gammadelta Treg cells, have been identified in human cancers. These
      Treg-cell subsets form a tumor suppressive microenvironment that presents a major
      barrier to successful anti-tumor immunotherapy. Thus, how to modulate the Treg
      cell function in tumor microenvironments is essential for cancer treatment and
      elimination. To date, there is no unique and selective marker for all subsets of
      Treg cells, and a combination of assays for Treg-associated markers and
      suppressive activity is still the most common way used to define these tumor
      associated Treg cells. In this chapter, we describe protocols to purify and
      characterize tumor-associated Treg cells from peripheral blood and TILs of cancer
      patients, which is critical for predicting clinical outcomes and monitoring the
      effects of tumor immunotherapy.

PMID- 20686959
TI  - Generation of cytotoxic T lymphocytes for immunotherapy of EBV-associated
      malignancies.
AB  - Current approaches for the treatment of tumours typically employ broad acting
      radiotherapeutic and chemotherapeutic approaches, which have led to high success
      rates but can be associated with unwanted side-effects. Cytotoxic T cell (CTL)
      based immunotherapy offers an alternative approach that is designed to
      specifically target protein antigens expressed in malignant cells and is thus
      likely to limit any adverse side-effects. Defining tumour-specific antigens is
      therefore critical for the successful application of CTL-based therapy. Epstein
      Barr virus (EBV)-associated malignancies offer an attractive target for CTL-based
      immunotherapy due to presence of virally encoded antigens in the malignant cells.
      Recent success in treating Epstein-Barr virus (EBV)-associated post-transplant
      lymphoproliferative disorder (PTLD) using cytotoxic T cell (CTL)-based
      immunotherapy has led to interest in the development of CTL-based immunotherapy
      to treat other EBV-associated malignancies in which antigen expression patterns
      are well defined but limited to a restricted number of proteins.

PMID- 20686960
TI  - Acquisition, preparation, and functional assessment of human NK cells for
      adoptive immunotherapy.
AB  - Human natural killer (NK) cells, a subset of peripheral blood lymphocytes that
      lack a T- or B-cell receptor, play a crucial role in the innate immune response
      to viruses and malignant cells. NK cells differentiate infected or malignant
      cells from normal cells by a complex balance between activating and inhibitory
      receptor-ligand interactions. Unlike T cells, NK cells do not proliferate in
      vitro in response to simple crosslinking of a single activating receptor. While
      many methods to study T-cell function and phenotype can also be applied to NK
      cells, this chapter addresses methods that are unique to the preparation and
      assessment of human NK cells for immunotherapy.

PMID- 20686961
TI  - Enhanced migration of human dendritic cells expressing inducible CD40.
AB  - Dendritic cells (DC) are the most potent antigen-presenting cells for priming and
      activating naive CD4(+) and CD8(+) T lymphocytes. This property has led to their
      use as a cellular vaccine in a number of clinical trials with promising results.
      However, the clinical efficacy of DC vaccines in patients has been
      unsatisfactory, probably because of a number of key deficiencies, including
      limited migration of ex vivo generated DCs to the secondary lymphoid tissues. To
      enhance human DC-based vaccines, we used the combination of an inducible CD40
      receptor (iCD40) along with TLR-4 ligation. The iCD40 receptor permits targeted,
      reversible activation of CD40. Using iCD40 in combination with
      lipopolysaccharides (LPS), we enhanced DCs migration in vitro upon escalation of
      the AP1903 dimerizer drug doses. This result suggests that the use of iCD40
      modified and LPS-stimulated DCs is a potent strategy in DC-based cancer
      immunotherapies.

PMID- 20686962
TI  - Differentiation of human embryonic stem cells into hematopoietic cells in vitro.
AB  - The ability of embryonic stem cells (ES) cells to form cells and tissues from all
      three germ layers can be exploited to generate cells that can be used to treat
      diseases. In particular, successful generation of hematopoietic cells from ES
      cells could provide safer and less immunogenic cells than bone cells, obviating
      the need for severe host preconditioning when transplanted across major
      histocompatibility complex barriers. To generate hematopoietic stem cells,
      protocols utilizing embryoid body (EB)-induced differentiation of human ES (hES)
      cells have been applied in the authors' laboratory. While this protocol results
      in targeted differentiation into hematopoietic cells, much remains to be done to
      improve these methods and make them more efficient.

PMID- 20686963
TI  - Gene therapy to improve migration of T cells to the tumor site.
AB  - One requirement for anti-tumor T cells to be effective is their successful
      traffic to tumor sites. Trafficking of T cells to lymphoid organs and peripheral
      tissues is a multistage process. Soluble and tissue-bonded chemokines interacting
      with chemokine receptors expressed by T lymphocytes certainly play a pivotal role
      in determining migration under physiologic conditions and during inflammation.
      Therefore a match between the chemokines the tumor produces and the chemokine
      receptors the effector T cells express is required. Since chemokine produced by
      the targeted tumor may not match the subset of chemokine receptors expressed by T
      cells, gene therapy can be used to force the expression of the specific chemokine
      receptor by effector T cells so that the anti-tumor activity of adoptively
      transferred anti-tumor T cells is maximized.

PMID- 20686964
TI  - Gene therapy to improve function of T cells for adoptive immunotherapy.
AB  - Adoptive immunotherapy with cytotoxic T cells has shown promising clinical
      results in patients with metastatic melanoma and post-transplant-associated viral
      infections. However, the antitumor effect of adoptively transferred tumor
      specific cytotoxic T lymphocytes (CTLs) is impaired by the limited capacity of
      these cells to expand within the tumor microenvironment. Administration of
      interleukin 2 (IL-2) has been used to overcome this limitation, but the systemic
      toxicity and the expansion of unwanted cells, including regulatory T cells, limit
      the clinical value of this strategy. To discover whether transgenic expression of
      lymphokines by the CTLs themselves might overcome these limitations, we evaluated
      the effects of transgenic expression of IL-2 and IL-15 in our model of Epstein
      Barr Virus-specific CTLs (EBV-CTLs). We found that transgenic expression of IL-2
      or IL-15 increased the expansion of EBV-CTLs in vitro and that these gene
      modified EBV-CTL had enhanced antitumor activity, while maintaining their antigen
      specificity. Although the proliferation of these cytokine gene transduced CTLs
      remained strictly antigen dependent, clinical application of this approach likely
      requires the inclusion of a suicide gene to deal with the potential development
      of T-cell mutants with autonomous growth. We found that the incorporation of an
      inducible caspase-9 suicide gene allowed efficient elimination of transgenic CTLs
      after exposure to a chemical inducer of dimerization, thereby increasing the
      safety and feasibility of the approach.

PMID- 20686965
TI  - Cytokine-FC fusion genes as molecular adjuvants for DNA vaccines.
AB  - The use of gene constructs for DNA immunization offers several potential
      advantages over other commonly used vaccine approaches: (1) full-length cDNA
      provides multiple potential class I and class II epitopes, thus bypassing
      limitations of MHC restriction; (2) bacterial plasmid DNA contains immunogenic
      unmethylated CpG motifs (immunostimulatory sequences) that may act as a potent
      immunological adjuvant; and (3) DNA is relatively simple to purify in large
      quantities. The cDNA encoding the antigen of interest is cloned into a bacterial
      expression plasmid with a constitutively active promoter and this plasmid is
      injected into the skin or muscle where it is taken up by professional antigen
      presenting cells, particularly dendritic cells, either through direct
      transfection or cross-priming. One can further enhance or modulate the immune
      response through co-delivery of DNA encoding cytokines or chemokines, including
      cytokine-Fc fusion molecules. The latter use molecular techniques to fuse a
      cytokine to the Fc portion of IgG1, creating a chimeric molecule with functional
      activity. In the present chapter, we will outline the approach to develop
      cytokine-Fc fusion genes as molecular adjuvants and will use GM-CSF as an
      example.

PMID- 20686966
TI  - Pharmacology of anti-CD3 diphtheria immunotoxin in CD3 positive T-cell lymphoma
      trials.
AB  - Anti-CD3 recombinant diphtheria immunotoxin, A-dmDT(390)-bisFv(UCHT1), consists
      of the catalytic and translocation domains of diphtheria toxin fused to two
      single chain Fv fragments of an anti-CD3epsilon monoclonal antibody (UCHT1). A
      dmDT(390)-bisFv(UCHT1) is capable of killing CD3(+) T-lymphoma cells and normal T
      cells specifically in the femtomolar concentration range. To study pharmacology
      of A-dmDT(390)-bisFv(UCHT1) in patients with CD3(+) T-cell lymphoma in a phase I
      clinical trial, (1) highly sensitive bioassay using Jurkat cells for measuring
      drug levels, (2) ELISA for measuring anti-DT antibody titer, and (3) 5-color FACS
      analysis method for measuring changes of subtype T-cell population were
      developed. In addition to evaluating drug efficacy and pharmacokinetics in
      patients, it is important to correlate pre-existing anti-DT antibody levels with
      maximum drug concentration in serum and extent of T-cell depletion because pre
      existing anti-DT antibodies due to DPT (Diphtheria, Pertussis, and Tetanus)
      immunization can neutralize diphtheria immunotoxin. We observed that at the
      lowest treatment dose (2.5 microg/kg: twice daily for 4 days) A-dmDT(390)
      bisFv(UCHT1) depletes greater than 99.0% of normal T cells in all six patients
      for a short period of time (2-3 days) and that there is no association of C (max)
      and extent of T-cell depletion with the pre-existing anti-DT antibody titer.

PMID- 20686967
TI  - Construction of human antibody gene libraries and selection of antibodies by
      phage display.
AB  - Recombinant antibodies as therapeutics offer new opportunities for the treatment
      of many tumor diseases. To date, 18 antibody-based drugs are approved for cancer
      treatment and hundreds of anti-tumor antibodies are under development. The first
      clinically approved antibodies were of murine origin or human-mouse chimeric.
      However, since murine antibody domains are immunogenic in human patients and
      could result in human anti-mouse antibody (HAMA) responses, currently mainly
      humanized and fully human antibodies are developed for therapeutic
      applications.Here, in vitro antibody selection technologies directly allow the
      selection of human antibodies and the corresponding genes from human antibody
      gene libraries. Antibody phage display is the most common way to generate human
      antibodies and has already yielded thousands of recombinant antibodies for
      research, diagnostics and therapy. Here, we describe methods for the construction
      of human scFv gene libraries and the antibody selection.

PMID- 20686968
TI  - Identification of immunogenic peptides of the self-tumor antigen: our experience
      with telomerase reverse transcriptase.
AB  - The general approach, termed reverse immunology, to predict and identify
      immunogenic peptides from the sequence of a gene product of interest has been
      postulated to be a particularly efficient, high-throughput approach to discover
      tumor antigens. This laboratory has successfully identified immunogenic peptides
      of the human telomerase reverse transcriptase (hTERT), a self-tumor antigen, by
      using a multi-step approach. These steps include the following: the use of
      predictive bioinformatics algorithms, molecular methods to identify tumor
      specific transcripts, prediction of proteasomal cleavage sites, peptide-binding
      prediction to HLA molecules and experimental validation, assessment of the in
      vitro and in vivo immunogenic potential of selected peptide antigens, isolation
      of specific cytolytic T lymphocyte clones, and final validation in functional
      assays of tumor cell recognition. This laboratory, and others have used similar
      methods to identify immunogenic peptides of self-tumor antigens, and many of
      those peptides are included in vaccines currently tested in clinical trials.

PMID- 20686969
TI  - Rescue, amplification, purification, and PEGylation of replication defective
      first-generation adenoviral vectors.
AB  - Adenoviral gene therapy vectors have been widely studied and used. Their
      extremely high transduction efficiency and gene delivery in vivo make them
      attractive for cancer gene therapy approaches. While they are robust, they are
      also very immunogenic. One approach to mitigate the immunogenicity of
      adenoviruses and to evade neutralizing antibodies is to coat the virus with the
      hydrophilic polymer polyethylene glycol (PEG) (1). This chapter details the steps
      involved when going from recombinant adenoviral vector plasmid all the way to
      validated PEGylated adenovirus product.

PMID- 20686970
TI  - Adenovirus-mediated interleukin (IL)-24 immunotherapy for cancer.
AB  - Interleukin-24 (IL-24) is a member of the IL-10 cytokine family. IL-24, also
      known as melanoma differentiation associated gene 7 (mda-7), is a unique cytokine
      in that it has cytokine properties and functions as a novel tumor suppressor
      gene. Studies by us and other investigators using viral and non-viral vectors
      have demonstrated IL-24 overexpression in human cancer cells inhibited tumor
      growth both in vitro and in vivo. A majority of these studies using
      immunodeficient animal models have focused on demonstrating the direct anticancer
      properties of IL-24. Very few studies have focused on studying the
      immunotherapeutic properties of IL-24 despite it being reported to function as a
      Th1 cytokine. A phase I clinical trial using an adenovirus vector expressing IL
      24 (Ad-IL24/INGN241) reported Ad-IL24 treatment of cancer patients resulted in
      changes in cytokines and T cells. However, well-designed and detailed preclinical
      studies to support the clinical findings are warranted. Demonstrating immune
      modulation by IL-24 will provide a rationale for developing IL-24-based
      immunotherapeutic approaches for cancer treatment.In the present chapter, we
      provide experimental details for conducting IL-24-based immunotherapy studies. As
      it is not possible for the authors to cover all of the information the authors
      recommend reading other immunology-based literature and procedures for a better
      understanding of conducting preclinical studies.

PMID- 20686971
TI  - Liposomes for gene transfer in cancer therapy.
AB  - We developed improved liposomes that produce efficacy for the treatment of
      cancer, cardiovascular diseases, and HIV-1-related diseases in small and large
      animal models. Because our processes are reproducible, we have standard operating
      procedures (SOPs) for the cGMP manufacture of these reagents that have been
      approved by the Food and Drug Administration for use in phase I/II clinical
      trials.

PMID- 20686972
TI  - Oncolytic HSV as a vector in cancer immunotherapy.
AB  - It is well documented that immunotherapy has a great potential for cancer
      treatment. The ideal cancer immunotherapeutic strategies should be relatively
      simple, but able to trick the host's immune system to elicit a robust immune
      response to the tumor target. Herpes Simplex Virus (HSV) has been engineered for
      the purpose of oncolysis. These so-called oncolytic HSVs can selectively
      replicate within tumor cells, resulting in their destruction and in the
      production of progeny virions that can spread to adjacent tumor cells. In
      addition to their direct oncolytic effect, tumor lysis by oncolytic viruses
      releases tumor antigens in their native form and configuration in an
      individualized way. Immune responses thus generated would be more likely to
      recognize the original tumor than would tumor vaccines produced by other methods,
      most of which require extensive in vitro modification and manipulation. Several
      recently published studies have shown that HSV-elicited antitumor immune
      responses are an essential part of the overall antitumor effect produced by
      oncolytic HSVs, not only for controlling primary tumor growth, but also for
      preventing long distance metastases. In this chapter several key methods will be
      illustrated to monitor the immune response elicited by oncolytic HSVs.

PMID- 20686973
TI  - Generation of chimeric T-cell receptor transgenes and their efficient transfer in
      primary mouse T lymphocytes.
AB  - Gene modification of T cells with chimeric T-cell receptor (TCR) transgenes
      offers a novel way to generate tumor-specific T cells for cancer immunotherapy.
      Retroviruses have been utilized as the most common means of efficiently
      transducing primary T lymphocytes with these transgenes. In this section we
      describe methods for generation of chimeric TCR's and utilization of retroviral
      vectors for efficient transduction of these transgenes in primary mouse T
      lymphocytes.

PMID- 20686974
TI  - Multi-walled carbon nanotube (MWCNT) synthesis, preparation, labeling, and
      functionalization.
AB  - Nanomedicine is a growing field with a great potential for introducing new
      generation of targeted and personalized drug. Amongst new generation of nano
      vectors are carbon nanotubes (CNTs), which can be produced as single or multi
      walled. Multi-walled carbon nanotubes (MWCNTs) can be fabricated as biocompatible
      nanostructures (cylindrical bulky tubes). These structures are currently under
      investigation for their application in nanomedicine as viable and safe
      nanovectors for gene and drug delivery. In this chapter, we will provide you with
      the necessary information to understand the synthesis of MWCNTs,
      functionalization, PKH26 labeling, RNAi, and DNA loading for in vitro
      experimentation and in vivo implantation of labeled MWCNT in mice as well as
      materials used in this experimentation. We used this technique to manipulate
      microglia as part of a novel application for the brain cancer immunotherapy. Our
      published data show this is a promising technique for labeling, and gene and drug
      delivery into microglia.

PMID- 20686975
TI  - Cellular immunotherapy of cancer.
AB  - Standard therapies for many common cancers remain toxic and are often
      ineffective. Cellular immunotherapy has the potential to be a highly targeted
      alternative, with low toxicity to normal tissues but a high capacity to eradicate
      tumor. In this chapter we describe approaches that generate cellular therapies
      using active immunization with cells, proteins, peptides, or nucleic acids, as
      well as efforts that use adoptive transfer of effector cells that directly target
      antigens on malignant cells. Many of these approaches are proving successful in
      hematologic malignancy and in melanoma. In this chapter we discuss the advantages
      and limitations of each and how over the next decade investigators will attempt
      to broaden their reach, increase their efficacy, and simplify their application.

PMID- 20686976
TI  - Management of depression in older people with osteoarthritis: A systematic
      review.
AB  - OBJECTIVES: Osteoarthritis (OA) is the most common form of arthritis, and
      depressive symptoms are common in older people with arthritic pain. However,
      relatively little attention has been given to the efficacy of interventions that
      may be beneficial for older people with OA with concomitant depressive symptoms.
      METHODS: The aim of this review was to evaluate data from clinical trials testing
      the effectiveness of various interventions for older patients suffering from OA
      and depression. Systematic searches were conducted on MEDLINE, CINAHL, Scopus,
      PsychInfo, Web of Knowledge and Pubmed (January 1990-July 2009). RESULTS:
      Fourteen studies were identified and examined. Interventions highlighted in these
      studies were: patient education programmes (N = 3); cognitive behavioural therapy
      (CBT) (N = 2); depression care and pharmacological intervention (N = 2); and
      exercise therapy (N = 7). 11 out of 14 interventions showed some improvement in
      patients' depressive symptoms in the short term. Three of the interventions did
      not affect depressive symptoms on patients with OA. CONCLUSIONS: There was some
      evidence to suggest that the intervention of CBT, integrated depression care
      management and exercise therapy were associated with reduced depressive symptoms
      in the short term. However, the long-term benefits of depression management in
      patients with OA with co-morbid depression are unknown. Future well-controlled
      clinical trials are needed.

PMID- 20686977
TI  - Is exercise effective in promoting mental well-being in older age? A systematic
      review.
AB  - BACKGROUND: Promoting the mental well-being of older people has been neglected.
      AIM: To examine the clinical and cost-effectiveness of exercise and physical
      activity interventions on mental well-being in people aged 65+. DESIGN:
      Systematic review, meta-analysis, economic model. METHODS: Reports published in
      English, identified by searching 25 databases, 11 websites and references lists
      of systematic reviews. Eligible studies were those with a comparison or control
      group or offering qualitative evidence; exercise and physical activity
      interventions for people aged 65 and above living at home, in the community, in
      supported housing or in residential care homes; including outcome measures of
      mental well-being, not simply measures of depression or anxiety. Low-quality
      studies were excluded from the data synthesis. RESULTS: An overall effect of
      exercise on mental well-being was found (standardised effect size = 0.27; CI =
      0.14-0.40). The included interventions were designed for older people, targeted
      those who are sedentary and delivered in a community setting, primarily through a
      group-based approach led by trained leaders. As a minimum, the evidence would
      suggest two exercise sessions per week, each of 45 min duration. There is some
      indication that exercise can also improve the mental well-being of frail elders.
      Economic evidence indicated incremental cost-effectiveness ratios (compared with
      minimal intervention) of pound 7300 and pound 12,100 per quality adjusted life
      year gained for community-based walking and exercise programmes, respectively.
      CONCLUSIONS: Mental well-being in later life is modifiable through exercise and
      physical activity. To generalise the findings, there is a need for more evidence
      of effectiveness from older people in the UK.

PMID- 20686978
TI  - PTSD in older bereaved people.
AB  - Late life bereavement has been associated with psychological problems, mainly
      depression. A few studies indicated that posttraumatic stress disorder (PTSD) was
      an important issue in late life bereavement reactions. This study aimed to assess
      the prevalence of PTSD in recently bereaved older people compared with married
      controls and to investigate whether the loss of a spouse in old age, in contrast
      with earlier assumptions, could lead to PTSD. Two hundred and ninety-six Danish
      older bereaved people (mean age 73 years, 113 males) were chosen from national
      registers and assessed two months postbereavement. They were compared with a
      control group of 276 married older people. The prevalence of PTSD and depression
      were measured through a self-report questionnaire. Results showed that 16% of the
      bereaved and 4% of the control group had a PTSD diagnosis (ES = 0.35; Cohen's d =
      0.74). Additionally, 37% of the bereaved and 22% of the control group had mild to
      severe depression (ES = 0.19; Cohen's d = 0.37). The results suggested that late
      life spousal bereavement result in PTSD with equal frequency to general samples
      of bereaved persons. Furthermore, the prevalence of PTSD in the first months
      after bereavement was more elevated than the level of depression. This makes PTSD
      an important factor when studying late life bereavement reactions.

PMID- 20686979
TI  - APOE epsilon4 allele carriers: Biological, psychological, and social variables
      associated with cognitive impairment.
AB  - OBJECTIVE: The apolipoprotein (APOE) epsilon4 allele genotype is a risk factor
      for dementia, but not all people with the APOE epsilon4 allele develop cognitive
      impairment (CI). Among participants with the APOE epsilon4 allele (N = 664), we
      identified biological, psychological, and social variables that discriminate
      between participants who develop CI from those who do not. We then determined if
      these variables predicted CI in noncarriers (N = 1421). In the sample as a whole
      we then determined if each of these identified variables moderate the
      relationship between the APOE epsilon4 allele and CI. METHODS: We used data from
      a biracial community-dwelling sample of older adults. Data were collected at four
      time points over a 10-year period. Cognitive functioning was assessed at each
      wave, using the Short Portable Mental Status Questionnaire (SPMSQ). APOE
      genotyping was performed at Wave 3. RESULTS: Among APOE epsilon4 allele carriers,
      but not noncarriers, variables associated with CI included white race, female
      gender, low BMI, number of negative life events, and health problems (high blood
      pressure, heart disease, and stroke). In analyses testing for moderate effects
      and including the entire sample, significant interactions with APOE epsilon4
      allele and predictor variables revealed that white race, low BMI, stroke, heart
      disease, and negative life events had a greater effect on CI among those with the
      APOE epsilon4 allele compared to those without the allele. CONCLUSION: There are
      biological, psychological, and social variables associated with increased risk
      for CI among individuals with the APOE epsilon4 allele.

PMID- 20686980
TI  - The conversational mini-mental state examination: Estimating cognitive
      impairment.
AB  - Formal cognitive testing is an integral part of the mental state examination, and
      we aimed to test whether clinicians were able to predict the score on the mini
      mental state examination (MMSE) by watching a conversation between a person and
      the interviewer about their memory. A total of 41 professionals rated 30 patients
      generally the scores on the MMSE were underestimated and experienced
      professionals did worse than less experienced practitioners. The results
      underscore the need for formal cognitive assessment and the requirements for
      training in the administration of cognitive tests.

PMID- 20686981
TI  - Depressive symptoms and health problems among Chinese immigrant elders in the US
      and Chinese elders in China.
AB  - OBJECTIVES: Researchers speculate that depression tends to be more prevalent
      among immigrant elders due to their lack of resources, acculturation stress,
      language problems, and social isolation. However, other characteristics of
      elderly immigrants, such as the healthy immigrant effect, may counteract these
      potential risk factors. This study examined whether depressive symptoms differed
      between Chinese immigrant elders and their counterparts in China and whether
      health conditions were similarly associated with depressive symptoms in these two
      samples. METHODS: Depression and health information was collected from 177
      Chinese immigrant elders in Boston, the US in 2000 and from 428 education and
      gender-matched elders in Shanghai, China in 2003. RESULTS: Chinese immigrants had
      a significantly lower score on the modified Center for Epidemiologic Studies
      Depression Scale (CES-D) and its subscales: somatic symptoms and depressive
      affect. The association remained for the subscale depressive affect in
      multivariate analyses. Arthritis and back or neck problems were associated with a
      higher level of depressive symptoms among Chinese immigrants, while problems in
      walking were associated with depression among their counterparts in China. Pain
      was an underlying contributor to the association between depression and these
      health problems in both the groups. CONCLUSIONS: This study suggests that Chinese
      immigrant elders might be more resilient than their counterparts despite many
      challenges they face after moving abroad. With the growing number of older
      Chinese immigrants in the US, a better understanding of depressive symptoms is
      essential to provide culturally competent services to better serve this
      population.

PMID- 20686982
TI  - Need fulfillment in caring relationships: Its relation with well-being of
      residents in somatic nursing homes.
AB  - OBJECTIVES: Quality of life and well-being in nursing homes are becoming more
      important in research and practice. Based on self-determination theory, the
      objective of this study is to examine the contribution of need fulfillment in the
      caring relationship to residents' subjective well-being. It was expected that the
      relation of need fulfillment in the caring relationship with well-being is
      mediated by need fulfillment in general. METHOD: During interviews with 88
      residents of somatic nursing homes (age 50-97, mean age 78.6), perceptions of
      need fulfillment in the caring relationship, need fulfillment in general, and two
      components of subjective well-being, i.e., depressive feelings and life
      satisfaction, were measured. The hypotheses were tested using hierarchical
      multiple regression analyses and mediational analysis. RESULTS: As expected, the
      results indicated that need fulfillment in the caring relationship was related to
      lower levels of depressive feelings and more life satisfaction. Need fulfillment
      in general mediated the relation of need fulfillment in the caring relationship
      with depressive feelings. CONCLUSION: As suggested by the results, it can be
      concluded that high-quality caring relationships contribute to the need
      fulfillment of residents and their well-being. The quality of caring
      relationships is thus an important topic for further research. The field may
      especially benefit from longitudinal studies and studies that use observations of
      the caring relationship in addition to self-reports.

PMID- 20686983
TI  - 'Just helping': Children living with a parent with young onset dementia.
AB  - OBJECTIVES: While the consequences of caring for younger people with dementia
      have been a growing area of research, little is known about the children of these
      individuals. This study aimed to discover whether children of younger people with
      dementia can be compared to other young carers, the impact of their caring on
      mood, burden and resilience and what could promote coping. METHOD: In-depth
      interviews were carried out with 12 participants aged 11-18. A grounded theory
      methodology was used, supplemented with three quantitative measures. RESULTS:
      Four higher order categories were identified focusing on: discovering dementia;
      developing a new relationship; learning to live with it and going through it
      together. Few participants showed depressive symptomatology, but more than half
      showed high levels of burden and most showed moderate levels of resilience. A
      three-stage process model of adapting to dementia is proposed, with children
      moving through grief to emotional detachment and increased maturity. CONCLUSION:
      This study has implications for service development in light of the National
      Dementia Strategy and proposals for whole family approaches for young carers.
      Whole family working by both dementia and children's services could reduce the
      burden on children of people with young onset dementia.

PMID- 20686984
TI  - Enhanced measurement sensitivity of hopeless ideation among older adults at risk
      of self-harm: Reliability and validity of Likert-type responses to the Beck
      Hopelessness Scale.
AB  - OBJECTIVE: Responses to the Beck Hopelessness Scale (BHS) have been identified as
      a significant predictor of suicide-related ideation and self-harm, of note, to a
      greater degree than severity of depressive symptoms. The BHS is the most widely
      used instrument to assess this construct, yet concern has been expressed about
      the traditional true/false response format of this instrument. For this study, we
      obtained responses from older adults to a revised four-point Likert-type BHS
      response format. METHOD: A national sample of 117 older Canadians at risk of self
      harm was recruited from multiple sources for this study over a one-year period.
      Most participants were women (65%) with an average age of 68.47 years (SD = 9.02,
      range 50-92). RESULTS: Exploratory factor analysis suggests the existence of two
      factors labeled Powerlessness/Disappointment and Negative Future Expectancies.
      Concurrent validity of this two-factor model of BHS responses is provided vis-a
      vis suicide-related ideation subsequent to statistical control for socio
      demographic factors, physical health, and depressive symptomatology. Of note, the
      relative contribution to the measurement of BHS factors is proportionately equal
      and greater than all other independent variables. CONCLUSION: We contend that
      this revised BHS response format may be appropriate for use in clinical and
      research applications though replication with other samples and populations is
      warranted.

PMID- 20686985
TI  - Depression in relation to purpose in life among a very old population: A five
      year follow-up study.
AB  - OBJECTIVES: To investigate the relationship between purpose in life and
      depression and, in a five-year follow-up investigate whether purpose in life,
      adjusted for different background characteristics, can prevent very old men and
      women from developing depression. METHODS: A cross-sectional study included 189
      participants (120 women and 69 men) 85-103 years of age living in a county in
      northern Sweden. Those who had not been diagnosed as depressed at baseline were
      included in the five-year follow-up study (n = 78). Depression was assessed using
      the Geriatric Depression Scale-15, the Organic Brain Syndrome scale, the
      Montgomery-Asberg Depression Rating Scale, and Diagnostic and Statistical Manual
      of Mental Disorders-IV criteria. Purpose in life was assessed with the Purpose in
      Life (PIL) scale. RESULTS: In the cross-sectional study, 40 participants out of
      189 (21.2%) were depressed, and those with depression had significantly lower PIL
      scores (mean score 107 vs. 99, p = 0.014). In the follow-up study, 78 persons
      were available for the assessment of depression. Of those, 21 (26.9%) were
      diagnosed as depressed and their mean PIL score at baseline was 106 (SD = 17.4)
      versus 108 (SD = 16.0, p = 0.750) among those not depressed. Using multivariate
      logistic regression analysis controlling for possible confounders, we found no
      association between purpose in life and the risk of developing depression after
      five years (OR = 1.0, 95% CI 0.97-1.03). CONCLUSIONS: The results show a
      significant inverse relationship between purpose in life and depression in the
      cross-sectional study; however, a high PIL score does not seem to serve very old
      people as a protection against the risk of developing depression.

PMID- 20686986
TI  - Statement of retraction.

PMID- 20686987
TI  - Medical decisional capacity among children with HIV.
AB  - Medical decisional capacity (DC) refers to the ability to understand, appreciate,
      and make meaningful decisions about one's health. This is an important construct
      for children living with HIV whose involvement in their medical care has
      important implications for disease management. In this study, we assessed the
      relationship among DC, developmental stage, intellectual ability, and social
      emotional functioning of children with and without HIV infection (n=50). We
      hypothesized a positive correlation between variables, but did not expect to find
      a difference in DC between groups. Results provided partial support for our
      hypotheses. There was a positive relationship between developmental stage and
      understanding, which is but one dimension of DC. Children with HIV infection
      obtained significantly lower scores on measures of intellectual and adaptive
      functioning, but there was no significant difference in DC between groups.
      Findings suggest that children living with HIV have the capacity to meaningfully
      participate in their healthcare despite lower intellectual and adaptive
      functioning.

PMID- 20686988
TI  - Reliable data and indicators in safety research.

PMID- 20686989
TI  - Addressing the worst cases.

PMID- 20686990
TI  - Determination of carbon isotope ratios of methanol and acetaldehyde in air
      samples by gas chromatography-isotope ratio mass spectrometry combined with
      headspace solid-phase microextraction.
AB  - Isotopic signatures of atmospheric methanol and acetaldehyde have the potential
      to improve our ability to quantitatively assess their importance in atmospheric
      chemistry. However, isotopic measurements of atmospheric methanol and
      acetaldehyde and their individual source and sink processes have been limited. In
      this study, we examined gas chromatography-isotope ratio mass spectrometry
      combined with headspace solid-phase microextraction to measure the carbon isotope
      ratios of methanol and acetaldehyde in air samples. The method enabled us to
      determine carbon isotope ratios with a precision (1 standard deviation) of +/-
      0.6 0/00 for 20 ml of air sample containing more than 3 ppm of methanol and +/-
      0.7 0/00 for 20 ml of air sample containing more than 2 ppm of acetaldehyde.
      Moreover, the applicability of this method to determine isotope ratios of
      methanol and acetaldehyde emitted from detached plant leaves was demonstrated.

PMID- 20686991
TI  - Performance factors in the new combined event of modern pentathlon.
AB  - The aims of this study were to determine (1) the individual tactics employed by
      elite modern pentathletes within each discipline of the new combined running
      shooting event, and (2) the consequences of these strategies on overall
      performance. For 36 male pentathletes competing in a World Cup event, we measured
      running velocity, transition time, shooting time, shooting accuracy, and delay
      per shot. Performances of the top third of athletes, middle third of athletes,
      and the bottom third of athletes in the combined event were compared. The
      difference in overall performance between the top third and middle/bottom thirds
      was predominately associated with better shooting accuracy (79 +/- 13%, 68 +/-
      12%, and 64 +/- 10% success rate for top, middle, and bottom third, respectively)
      and faster shooting time (86 +/- 16 s, 109 +/- 19 s, and 117 +/- 23 s for top,
      middle, and bottom third, respectively). No significant differences in running
      velocity, transition time or delay per shot were observed among the three groups.
      All the competitors started significantly faster over the first 200 m of each of
      the three 1-km running stages. The last third of the approximately 3-km race was
      completed significantly faster by all athletes (P < 0.05). The main finding was
      that the best performers of the combined event distinguished themselves due to
      their greater shooting accuracy.

PMID- 20686992
TI  - Development and validation of the Decision-Specific Reinvestment Scale.
AB  - Items from the Reinvestment Scale were modified to create a decision-specific
      version of the scale. Principal components analysis of responses from 165
      participants revealed one-, two-, three-, and four-factor solutions for the
      Decision-Specific Reinvestment Scale. Confirmatory factor analysis of responses
      from a second sample of 111 participants revealed that a 13-item two-factor
      solution showed the best fit. The first factor comprised six items referring to
      conscious monitoring of the process involved in making a decision, and was termed
      decision reinvestment. The second factor, decision rumination, comprised seven
      items related to focus on negative evaluations of previous poor decisions. In an
      initial assessment of predictive validity, Decision-Specific Reinvestment Scale
      scores of 59 skilled team sport players were found to be highly correlated with
      coaches' ratings of players' tendency to choke under pressure (r = 0.74), with
      high Decision-Specific Reinvestment Scale scores indicating greater
      susceptibility to poor decision-making under pressure. It was concluded that the
      Decision-Specific Reinvestment Scale highlights a performer's predisposition to
      engage in behaviours detrimental to performance under pressure, namely decision
      reinvestment and decision rumination.

PMID- 20686993
TI  - Antioxidant defence and inflammatory response in professional road cyclists
      during a 4-day competition.
AB  - Cycling competitions represent an important physical overload even for well
      trained individuals. In six professional cyclists, we studied the adaptive
      oxidative and anti-inflammatory response to a 4-day road cycling competition and
      its relationship with melatonin, an antioxidant and anti-inflammatory stress
      hormone. Blood and urine samples were collected before and after the competition.
      Plasma lipid peroxidation, cytokines (interleukin-1beta, interleukin-6, and
      tumour necrosis factor-alpha), creatine kinase and other metabolic markers,
      melatonin, erythrocyte glutathione, and glutathione peroxidase and reductase
      activities were measured. Urinary excretion of 6-sulphatoxymelatonin was
      analysed. Lipid peroxidation increased after the competition, but the erythrocyte
      glutathione pool remained unchanged. Changes in both glutathione peroxidase and
      reductase activities probably account for the recycling of glutathione after
      exercise. Interleukin-6 (216%) and tumour necrosis factor-alpha (159%) but not
      interleukin-1beta increased after exercise. A parallel increase in plasma
      melatonin concentrations was detected, whereas metabolic markers, including
      creatine kinase, showed minor modifications. Thus, professional cyclists display
      an adaptative response to the physical overloads in the competitions for which
      they are trained. Consequently, they seem to be able to regulate efficiently the
      intracellular oxidative stress, and prevent an exaggerated pro-inflammatory
      cytokines induction. A modulator role of melatonin in these adaptive responses is
      also supported.

PMID- 20686994
TI  - Evaluating attentional and affective changes following an acute exercise bout
      using a modified dot-probe protocol.
AB  - A large body of literature advocates exercise as a successful intervention for
      increasing positive affect while also reducing negative affect and anxiety.
      Questions concerning the mechanisms driving these effects remain unanswered,
      particularly considering theorized attentional adaptations that may be elicited
      by acute exercise bouts. We investigated pre- and post-exercise attentional bias
      to examine possible attentional explanations that may account for these reported
      changes in affect. On separate visits to the laboratory, 30 high trait anxious
      participants completed 30 min of exercise on a cycle ergometer at 70% of their
      heart rate reserve, or completed a 30-min quiet rest protocol. During each
      intervention, pre-test and post-test modified dot-probe assessments of
      attentional bias were completed, as were a series of self-report anxiety and
      affect questionnaires. Attentional bias scores and reaction times were
      calculated. Post-exercise dot probe performance did not vary significantly as a
      function of the affective valence of presented stimuli. As hypothesized, however,
      positive affect and reaction time improved significantly following exercise
      compared with the pre- and post-rest conditions and the pre-exercise condition,
      suggesting that exercise facilitates a broadening of attentional scope.
      Implications of these findings and future directions are discussed within the
      context of traditional and contemporary theories of dispositional affect and
      state-specific emotional responses.

PMID- 20686995
TI  - The effect of breast support on the kinematics of the breast during the running
      gait cycle.
AB  - Although breast pain has been related to vertical breast displacement and
      velocity, the influence of breast support on multi-planar breast kinematics and
      breast comfort has yet to be ascertained. The aims of this study were to
      investigate multi-planar breast displacement, velocity, and acceleration with and
      without breast support during running and to establish the correlation with
      breast comfort. Fifteen females ran at 2.8 m x s(-1) in no bra, an everyday bra,
      and a sports bra. Three-dimensional coordinates of breast and body markers were
      tracked during ten gait cycles and following each trial the participants rated
      their breast comfort. Relative breast displacement was calculated and derived for
      velocity and acceleration. Vertical breast displacement, velocity, and
      acceleration peaked at, before, and after mid-stance, respectively. The patterns
      of displacement and velocity trajectories were unaffected by increasing breast
      support, though the magnitudes were significantly reduced. The magnitude and
      trajectory of breast acceleration was unaffected by increasing breast support and
      showed no correlation with comfort. Breast velocity displayed the strongest
      relationship to comfort (r = 0.61). Considerable mediolateral and anteroposterior
      breast kinematics were identified, suggesting that future studies and bra design
      may benefit from three-dimensional analysis. In conclusion, improvements in
      breast support may be defined by reductions in breast velocity and displacement.

PMID- 20686996
TI  - Offside decision making in the 2002 and 2006 FIFA World Cups.
AB  - The first objective of the present study was to examine the accuracy of offside
      judgements of assistant referees during the 2006 World Cup and to compare overall
      results with performances of assistant referees during the 2002 World Cup.
      Second, we also examined underlying mechanisms leading to incorrect decisions.
      According to the definition used for the 2002 World Cup, the results revealed a
      decrease in the number of incorrect flag signals during the 2006 (24/240 or
      10.0%) compared with the 2002 World Cup (58/222 or 26.1%) (P < 0.001). For
      accuracy of all potential offside situations, according to a new definition (with
      the attacker 2 m in front or behind the second-last defender), the error
      percentage was 7.6% (17 flag errors and 9 non-flag errors out of 342 situations).
      Overall, quality of offside decisions was not influenced by the position of the
      assistant referee relative to the offside line. In addition, flag errors can best
      be explained by the perceptual illusion induced by the flash-lag effect.

PMID- 20686997
TI  - A new method to measure rolling resistance in treadmill cycling.
AB  - The purpose of this study was to evaluate a new method of measuring rolling
      resistance in treadmill cycling and to establish its sensitivity and
      reproducibility. One participant was asked to keep a bicycle in equilibrium on a
      treadmill without pedalling at a constant speed of 5.56 m x s(-1), which was held
      in place in the front by a dynamometer. For each condition, the method consisted
      of 11 measurements of the force required to hold the cycle at different treadmill
      slopes (0-10%, increment 1%). The coefficient of rolling resistance was
      calculated based on the forces applied to the bicycle in equilibrium. To test the
      sensitivity of the method, the bicycle was successively equipped with three tyre
      types (700 x 28, 700 x 23, 700 x 22) and inflation pressure was set at 150, 300,
      600, 900, and 1100 kPa. To test the reproducibility of the method, a second
      experimenter repeated all measurements done with the 700 x 23 tyres. The method
      was sensitive enough to detect an effect of both tyre type and inflation pressure
      (P < 0.001: two-way ANOVA). The measurement of the coefficient of rolling
      resistance by two separate experimenters resulted in a small bias of 0.00029 (95%
      CI, -0.00011 to 0.00068). In conclusion, the new method is sensitive and
      reliable, as well as being simple and affordable.

PMID- 20686998
TI  - Oxygenation and EMG in the proximal and distal vastus lateralis during submaximal
      isometric knee extension.
AB  - Muscle oxygenation responses are reportedly greater in the distal muscle region
      than in the proximal muscle region. We combined near infrared spectroscopy and
      electromyography (EMG) to determine whether regional differences in oxygenation
      are associated with differences in (1) muscle activation and/or (2) fatigue
      development. Nine males performed 2-min sustained isometric knee extensions at
      15% and 30% maximum voluntary contraction during which oxygenation and EMG were
      recorded simultaneously from proximal and distal locations of the vastus
      lateralis muscle. Near infrared spectroscopy variables for oxygen saturation
      (StO(2)%) were initial slope at contraction onset, peak drop, and recovery slope
      at contraction end. Electromyography produced the root mean square to indicate
      muscle activation and mean power frequency changes over time (decreasing slope)
      to indicate fatigue development. For StO(2)%, significantly greater peak drop and
      steeper recovery slope were found for the distal muscle region than for the
      proximal muscle region. Root mean square, however, was not different between
      locations. Mean power frequency decreased throughout the contractions but changes
      were not different between locations. Our results indicate that for modest
      submaximal contractions, regional differences in oxygenation are not associated
      with differences in muscle activation or with fatigue development (as interpreted
      by changes in mean power frequency over time).

PMID- 20686999
TI  - The effects of training on performance and performance-related states in
      individual elite athletes: a dynamic approach.
AB  - There are difficulties undertaking controlled training studies with elite
      athletes. Thus, data from non-elite performers are often presented in scientific
      journals and subsequently used to guide general training principles. This
      information may not be transferable or specific enough to inform training
      practices in an individual elite athlete. However, the nature of athletic
      participation at elite levels provides the opportunity to collect training data,
      performance-related variables, and performance data of elite athletes over long
      periods. In this paper, we describe how dynamic linear models provide an
      opportunity to use these data to inform training. Data from an elite female
      triathlete collected over a 111-day training period were used to model the
      relationship between training and self-reported fatigue. The dynamic linear model
      analysis showed the independent effects of the three modes of triathlon training
      on fatigue, how these can change across time, and the possible influence of other
      unmeasured variables. This paper shows the potential for the use of dynamic
      linear models as an aid to planning training in elite athletes.

PMID- 20687000
TI  - A negative semantic similarity effect on short-term order memory: evidence from
      recency judgements.
AB  - Speeded recency judgements were used to examine whether judgements concerning the
      relative temporal order in which two items were presented on a short eight-item,
      study list would be facilitated or hindered when the two items were from the same
      semantic category (related, R, items), relative to when they were from different
      categories (unrelated, U, items). Semantic similarity led to slower and less
      accurate recency judgements. To evaluate the extent that item memory contributes
      to recency judgement performance, I used speeded pair recognition and speeded two
      alternative forced-choice (2AFC) recognition trials, in which the stimuli and
      designs were the same as in the recency judgement test. The type of test trial
      was manipulated between subjects (recency judgement vs pair recognition) or
      within participants (recency judgement and 2AFC recognition). Regardless of the
      between- or within-participants manipulation of recognition vs order memory
      tests, the pattern of recognition performance was very different from the pattern
      of recency judgement performance, indicating that semantic similarity had a
      negative effect on order memory per se. The explanation of the current findings
      offered by position-based order memory theories is discussed.

PMID- 20687001
TI  - Diffusion of contingency management and attitudes regarding its effectiveness and
      acceptability.
AB  - Substance abuse counselors are critical as the key arbiters of clients'
      acceptance and use of innovative treatment techniques, with their potential
      support embedded in their knowledge of and attitudes towards particular
      innovations. In this analysis the authors examine the role of substance abuse
      counselors in the adoption of a psychosocial treatment innovation, contingency
      management (CM). Using data collected from 1140 counselors employed in a national
      sample of 318 public treatment centers, the authors examine theoretical
      predictors of counselors' knowledge of CM, and their attitudes regarding CM's
      effectiveness and acceptability. Findings suggest that lack of exposure to CM
      through program use and innovation-specific training is the most salient barrier
      to CM adoption and diffusion. The study also highlights the importance of social
      networks in the diffusion and acceptance of treatment innovations.

PMID- 20687002
TI  - Spiritual change in drug treatment: utility of the Christian Inventory of
      Spirituality.
AB  - The current study used data from reliability testing of the Christian Inventory
      of Spirituality (CIS) to (1) assess the utility of CIS in detecting differences
      in level of spirituality in residents of residential Christian faith-based
      substance abuse programs (RCFBSAPs); (2) test the hypothesis that residents who
      have been in the program for longer periods of time will have significantly
      higher levels of spirituality after controlling for relevant demographic
      characteristics; and (3) test the hypothesis that residents of programs that only
      use unlicensed staff and place higher importance on spirituality will have
      significantly higher levels of spirituality. A purposive sample of the cross
      sectional data from the reliability testing of the CIS was used (n = 253).
      Analysis supported the hypothesis. Demographic characteristics were not
      associated with level of spirituality. The CIS proved to be useful in
      discriminating levels of spirituality. Further research is needed to examine
      spiritual change using randomized pre-post test designs.

PMID- 20687003
TI  - Modified therapeutic community for co-occurring disorders: single investigator
      meta analysis.
AB  - This paper presents the results of a meta-analysis for a single investigator
      examining the effectiveness of the modified therapeutic community (MTC) for
      clients with co-occurring substance use and mental disorders (COD). The
      flexibility and utility of meta-analytic tools are described, although their
      application in this context is atypical. The analysis includes 4 comparisons from
      3 studies (retrieved N = 569) for various groups of clients with COD (homeless
      persons, offenders, and outpatients) in substance abuse treatment, comparing
      clients assigned either to an MTC or a control condition of standard services. An
      additional study is included in a series of sensitivity tests. The overall
      findings increase the research base of support for the MTC program for clients
      with COD, as results of the meta-analysis indicate significant MTC treatment
      effects for 5 of the 6 outcome domains across the 4 comparisons. Limitations of
      the approach are discussed. Independent replications, clinical trials, multiple
      outcome domains, and additional meta-analyses should be emphasized in future
      research. Given the need for research-based approaches, program and policy
      planners should consider the MTC when designing programs for co-occurring
      disorders.

PMID- 20687004
TI  - Effect of comorbid depression on substance use disorders.
AB  - The aim of the study was to investigate the effect of depression on pattern of
      substance use disorders (SUDs). Consecutive samples of (200) Egyptian male SUD
      inpatients were examined over 1-year period. Study and control samples were
      chosen. Study group consisted of 30 patients with comorbid substance dependence
      and depression. Control group consisted of 30 substance-dependent patients
      without depression. Semistructured interviews, Addiction Severity Index (ASI) and
      Hamilton Rating Scale for Depression (HDRS), were applied. Comparison between
      both groups showed significant differences for prescribed opioid use (100% versus
      86%), polysubstance use (73% versus 43%), frequency of suicidal attempts (86%
      versus 43%), mean of admissions to substance use treatment (SUT) units (5 versus
      2.2), mean of abstinence periods (3.8 versus 1.2); study group showed greater
      medical status impairment (P = .05), social and psychiatric impairment (P = .01).
      It was concluded that depression might affect SUD as regards type of substance
      used, pattern of use, suicide rate, duration of hospitalization, rate of
      rehospitalization, and finally medical, social, and psychiatric status
      impairment.

PMID- 20687005
TI  - Drug use in a rural secondary school in Kenya.
AB  - Alcohol abuse and alcohol-related use problems among adolescents are highly
      prevalent and are a major concern worldwide. This study estimated the prevalence
      of drug abuse, knowledge about drug abuse and its effect on psychosocial well
      being and induced behavioral problems among students of a public rural secondary
      school that admitted both girls and boys which offered both boarding and day
      school facilities. The students filled out a self-reporting substance use tool
      which measures the prevalence, frequency, and general patterns of substance use.
      Alcohol, tobacco, khat (catha edulis) and bhang (cannabis) were the most commonly
      reported substance of use, with user prevalence rates of 5.2%, 3.8%, 3.2%, and
      1.7%, respectively. Tobacco use was initiated at 10 years, while cannabis, hard
      drugs, khat, and alcohol were initiated at 11, 12, 13, and 15 years of age,
      respectively. Among the students 71% were aware that their schoolmates were on
      drugs and it was known by 49.8%, 41.7%, 37.6%, 44.3%, and 32.4% of these students
      that using alcohol, tobacco, khat, cannabis, and hard drugs, respectively was a
      behavioral problem in the school. Three quarters of the students were aware that
      use of drugs was harmful to their health, with majority (78.6%) indicating that
      drug users need help to stop the drug use behavior. However most (73.6%) of the
      students suggested drug users in school should be punished. The drug use
      behavioral problems included school dropout, poor scholastic attainment, drunken
      driving, delinquency, and adolescence pregnancy which threaten the stability of
      the education system, family as an institution (family difficulties) and society
      at large. Therefore, teachers have an added burden of playing an active role in
      guidance and counselling the survivors of drug abuse, a pandemic facing teaching
      institutions apart from instilling knowledge.

PMID- 20687006
TI  - Media exposure and tobacco, illicit drugs, and alcohol use among children and
      adolescents: a systematic review.
AB  - The authors systematically reviewed 42 quantitative studies on the relationship
      between media exposure and tobacco, illicit drug, and alcohol use among children
      and adolescents. Overall, 83% of studies reported that media was associated with
      increased risk of smoking initiation, use of illicit drugs, and alcohol
      consumption. Of 30 studies examining media content, 95% found a statistically
      significant association between increased media exposure and negative outcomes.
      Similarly, of the 12 studies evaluating the quantity of media exposure, 67%
      reported an association with a negative outcome. Overall, all 17 of the
      identified longitudinal studies supported a causal association between media
      exposure and negative outcomes over time. The evidence was strongest for links
      between media exposure and tobacco use; it was moderate for illicit drug use and
      alcohol use. Substantial variability in methodological rigor across studies and
      expanding definitions of media exposure contribute to persistent gaps in the
      knowledge base.

PMID- 20687010
TI  - Electrophysiological correlates of face distortion after-effects.
AB  - When observers are exposed to a distorted face the perceived configuration of a
      subsequently presented face is altered, a phenomenon called face distortion after
      effect (FDAE). We compared the face-related components of the event-related
      potential (ERP) after adaptation to noise images--veridical and distorted faces.
      We found large bilateral adaptation effects on the P100 and N170 components that
      are related to face detection. Moreover, we found smaller adaptation effects on
      the N170, recorded over the right hemisphere, which can be related to the
      behavioural distortion after-effect and to face configurations. Our results
      suggest that the observed ERP adaptation effects are general for various steps of
      face processing and that the FDAEs similarly to gender after-effects are related
      to the early face-specific ERP components.

PMID- 20687009
TI  - Aversive conditioning under conditions of restricted awareness: effects on
      spatial cueing.
AB  - In the literature on aversive conditioning there is still debate on the role of
      awareness. According to some authors, affective learning can occur with or
      without contingency learning (dual-process model), whereas others argue that a
      single process produces both affective responses and contingency knowledge.
      Although many studies have investigated these models, the results to date are
      inconclusive. Based on a review of the literature, a new series of experiments
      was designed to examine aversive conditioning in the absence of contingency
      awareness. In the present study we examined the effects of subliminal aversive
      conditioning on a spatial cueing task. Awareness was stringently tested after
      conditioning. Three kinds of awareness were distinguished: contingency awareness
      (awareness of the CS-US contingencies, where CS is the conditioned stimulus, and
      US is the unconditioned stimulus), perceptual awareness (awareness of the
      perceptual differences between the CSs), and US expectancy (awareness of a threat
      feeling when confronted with the CS+, but not when confronted with the CS-). The
      results of three experiments demonstrated that responses on the spatial cueing
      task were modulated by subliminal aversive conditioning. Importantly, none of the
      participants was contingency aware or able to perceptually discriminate between
      the conditioned stimuli. However, in Experiment 3, only those participants
      showing some level of postconditioning expectancy awareness exhibited
      conditioning effects. These experiments suggest that subliminal aversive
      conditioning produces small but significant effects, which may be modulated by
      expectancy awareness.

PMID- 20687011
TI  - [Pathological gambling--what do we know?].
AB  - According to epidemiological studies, there are 103 000-290 000 people in Germany
      afflicted by pathological gambling. In many cases the disorder remains hidden for
      a long time with only a few of the problematic or pathological gamblers seeking
      help in the professional helping network. Focussing on the relevant results for
      Germany, this review summarizes the recent research concerning "pathological
      gambling". The main topics are diagnosis, nosological status, epidemiology,
      gender-related differences and common screening instruments. Furthermore, the
      increasing probability for the development of pathological gambling upon existing
      other psychiatric disorders, e. g. personality disorder, mood and anxiety
      disorders, substance-related disorders or ADHD, is discussed as well as the
      current approaches in treatment.

PMID- 20687013
TI  - [Future psychotherapists? Vocational plans and motivation for choosing
      psychotherapy as a career in german psychology students].
AB  - BACKGROUND: in Germany psychology students can be seen as the major personal
      resource in psychotherapy. Nevertheless there are few studies on their vocational
      plans and their interest in psychotherapeutic training. METHOD: 480 psychology
      students completed a self-developed questionnaire on their career expectations.
      RESULTS: 90% of respondents report interest in clinical work and
      psychotherapeutic training. Most frequently they mention improving therapeutic
      competencies and career options as pros and current training requirements as
      cons. Their theoretical orientation (38% behaviour therapy, 19% psychodynamic
      therapy) is associated with their psychotherapeutic knowledge, study conditions
      and respondent's characteristics. CONCLUSIONS: psychology students consider
      working and training conditions for psychologists and psychotherapists, when
      thinking about their future career.

PMID- 20687012
TI  - [Depression, social support and compliance in patients with chronic heart
      failure].
AB  - Depressive patients with chronic heart failure (CHF) show less social integration
      and greater physical impairment as well as poorer compliance than non depressive
      CHF patients. Using multiple regression analyses, this study (n=84) investigated
      a potential mediating effect of depression on the relationship between compliance
      and both social support and physical functioning. Results did not support the
      hypothesized mediating effect of depression. However, the variables age,
      depression, left ventricular ejection fraction (LVEF) and social support were
      associated with self-reported compliance. Therefore, a lack of social support and
      depression should be considered as possible reasons, if patients are noncompliant
      during the treatment process.

PMID- 20687014
TI  - [Gender-specific predictors of institutionalisation in the elderly--results of
      the Leipzig longitudinal study of the aged (LEILA 75+)].
AB  - OBJECTIVE: Especially given the different socialization and life conditions of
      men and women, it could not be assumed that factors leading to nursing home
      admission (NHA) can be equally applied to both genders. We aimed to determine
      gender-specific predictors of NHA. METHODS: Data were derived from the Leipzig
      Longitudinal Study of the Aged, a population-based study of individuals aged 75
      years and older. 1,058 older adults were interviewed six times on average every
      1.4 years. Sociodemographic, clinical, and psychometric variables were obtained.
      Cox proportional hazards regression was used to determine predictors of NHA.
      RESULTS: 10.3 % of men and 19.5 % of women (p < 0.001) were admitted to nursing
      home during the study period. The mean time to nursing home was 7.2 years for men
      and 6.8 years for women. Characteristics associated with a shorter time to NHA
      were increased age for men and women; cognitive impairment, poor self-rated
      health status, and less than two specialist's visits in the preceding 12 months
      for women, and being unmarried, moderate educational status, and hospitalization
      in the preceding 12 months were predictors of NHA for men. CONCLUSIONS: Gender
      differences in prediction of NHA do actually exist. The inclusion of gender
      specific factors in design and application of interventions to support
      individuals at home and delay or prevent NHA appears to be warranted.

PMID- 20687015
TI  - [Increased anxiety and depression as long-term consequences of political
      imprisonment].
AB  - OBJECTIVE: By recent estimates, 200,000 persons were imprisoned for political
      reasons in the German Democratic Republic (GDR) between 1949 and 1989. Former
      political prisoners suffer from the experience of political persecution also in a
      long-term. The aim of this study was to assess long-term effects on anxiety and
      depression. METHODS: Anxiety and depression were assessed by using the Hospital
      Anxiety and Depression Scale, German version (HADS). RESULTS: The anxiety of the
      former political detainees is significantly increased in comparison to an age-
      and gender matched subsample of the general population (10 vs. 4,8; p < 0,001,
      effect size d = 1,33). The same applies to the depression (9.7 vs. 5,6; p <
      0,001; effect size d = 0,92). CONCLUSIONS: Even many years after the political
      detention people report highly increased anxiety and depression.

PMID- 20687016
TI  - Retrospective analysis of chronic hepatitis D in a West German University Clinic
      over two decades: migratory pattern, prevalence and clinical outcome.
AB  - BACKGROUND/AIMS: Epidemiology, clinical features and long term-course of chronic
      hepatitis D were addressed in a non-endemic Central European area. METHODS: Sixty
      seven patients with chronic hepatitis D were identified among 1307 HBsAg carriers
      at the university hospital Dusseldorf during two decades (1989 - 2008) and
      followed for a mean of 7 +/- 6 years. Forty-one of these were treated with IFN
      alfa for at least six months. RESULTS: Hepatitis D prevalence increased from 4.1
      to 6.2 % among HBsAg carriers during the two decades (p < 0.06). Patients
      originating from the former Soviet Union (32.1 vs. 46.2 %) and Africa (0 vs. 17.9
      %) became more frequent whereas the prevalence of patients from Southern Europe
      declined (46.5 vs.17.9 % p < 0.03). The time span between the diagnosis of
      hepatitis B and D was 4.8 +/- 7 years (p < 0.0001). A sustained virological
      response to interferon-alfa was achieved in 19.5 % of the patients. The yearly
      incidence rates for death, HCC and complications were 3.2 %, 2.7 % and 8 % among
      patients with liver cirrhosis. Estimated survival and complication-free survival
      during 12 years were 72 % and 45 % in cirrhotic compared to 100 % in non
      cirrhotic patients (p < 0.008 and p < 0.0001, respectively). CONCLUSION:
      Hepatitis D in western Germany appears to be on the increase and has a migration
      background that should be considered in clinical practice. Clinical outcome and
      response to IFN are as poor as in endemic regions, indicating the need to improve
      early diagnosis.

PMID- 20687017
TI  - Krefeld CONTRA study: conventional peroral Esophago-Gastro-Duodenoscopy (EGD) vs.
      transnasal EGD--a prospective and randomised study with independent evaluation of
      conscious sedation, endoscope diameter, and access path.
AB  - BACKGROUND: The guidelines of the German Gastroenterology Society (Deutsche
      Gesellschaft fur Verdauungs- und Stoffwechselkrankheiten, DGVS) demand the
      presence of an additional qualified person solely responsible for patient
      monitoring during sedated endoscopy. Transnasal esophagogastroduodenoscopy (EGD)
      allows easy access to the upper gastrointestinal tract and may avoid the
      complications induced by conscious sedation and reduce medical costs. PATIENT AND
      METHOD: 120 patients referred to diagnostic EGD were assigned to six groups:
      group 1, unsedated peroral EGD with normal-caliber endoscope; group 2, unsedated
      peroral EGD with small-caliber endoscope; group 3, sedated peroral EGD with
      normal-caliber endoscope; group 4, sedated peroral EGD with small-caliber
      endoscope; group 5, unsedated transnasal EGD with small-caliber endoscope; group
      6, sedated transnasal EGD with small-caliber endoscope. Outcome parameters
      included objective (duration, oxygen saturation) and subjective measures
      (standardised visual analogue scales) of the endoscopy staff (handling,
      insertion, retroflexion, tolerability, overall assessment) and patients (pain,
      unpleasantness, sore throat, choking, gagging, meteorism, anxiety,
      acceptability). RESULTS: The patients were comparable according to age, sex,
      anxiety, and respiratory function before EGD. Sedoanalgesia was without effect on
      EGD handling and duration, patient tolerability and overall assessment by
      endoscopists and assistants. Negative effects of sedoanalgesia (decreased oxygen
      saturation, patient acceptability) were much lower and without significance for
      transnasal compared to peroral EGD. Patient tolerability and acceptability of the
      endoscopic staff (handling, insertion, retroflexion) were significantly better
      for the small-caliber endoscope. Duration of unsedated transnasal EGD was
      slightly but significantly longer, pain, unpleasantness, and anxiety slightly but
      significantly higher compared to sedated peroral EGD. However, these differences
      could no loner be detected seven days after endoscopy. Cost analysis revealed
      major advantage for transnasal EGD. CONCLUSION: Unsedated transnasal EGD may
      replace diagnostic peroral EGD, reduces costs with acceptable patient discomfort
      and has advantagous acceptability of the endoscopic staff.

PMID- 20687018
TI  - [Severe aplastic anaemia in six children after non-A-E hepatitis without hepatic
      failure].
AB  - Aplastic anaemia can coincide with non-A-E hepatitis. Treatment follows a
      standardised study protocol of the German Society of Paediatric Oncology and
      Haematology (GPOH). Patients receive immunosuppression and/or bone marrow
      transplantation. We present six cases of aplastic anaemia after non-A-E hepatitis
      with different courses. In four of these children illness first presented with
      acute gastroenteritis. Five out of six children fully recovered, two of these
      with immunosuppression alone, three after bone marrow transplantation. One
      patient died due to complications of the bone marrow transplantation. In two
      patients steroid therapy was carried out to treat the hepatitis. This did not
      have any effect on the course of their aplastic anemia. We emphasise this common
      combination of aplastic anemia following non-A-E hepatitis. This overview
      underlines the necessity of regular blood testing after non-A-E hepatitis. Often
      gastroenteritis seems to precede illness thus perhaps indicating an infectious
      trigger.

PMID- 20687019
TI  - [Lambliasis as differential diagnosis of MARSH type 3b].
AB  - Giardia lamblia is the most common human parasite with a worldwide distribution
      and fecal-oral way of transmission. Diagnostic procedures include stool
      examination and gastroduodenoscopy with biopsy or secret aspiration. In most
      cases histology reveals a dense accumulation of the parasites on the surface of
      the duodenal mucosa with no or only slight inflammation. In rare cases, a dense
      inflammatory infiltrate with severe mucosal atrophy and increased count of
      intraepithelial lymphocytes may be seen. If in such cases the amount of parasites
      is low, the histological picture may mimic celiac disease. The two presented
      cases demonstrate the close morphological relationship and show the importance of
      considering giardiasis in the differential diagnosis in patients with suspected
      celiac disease.

PMID- 20687020
TI  - [Current aspects of the pathology and differentiation of extranodal marginal zone
      B-cell lymphoma, MALT-Type, and gastrointestinal diffuse large B-cell lymphoma].
AB  - The marginal zone B-cell lymphoma, MALT-type (MZBL, MT) is a low-grade B-cell
      lymphoma which is predominantly localised in the stomach with a typical
      morphology and cytogenetic pattern. The coexistence of a diffuse large B-cell
      lymphoma (DLBCL) with an MZBL, MT in the gastrointestinal tract is defined as a
      composite lymphoma (ComL) and represents a fascinating model of lymphoma
      progression. In this review we focus on current aspects regarding the molecular
      characterisation of MZBL, MT and gastrointestinal DLBCL and their mutual
      relationships.

PMID- 20687021
TI  - [Endoscopic-retrograde cholangiopancreatography in patients with surgical
      modification of anatomy].
AB  - Endoscopic retrograde cholangiopancreatography (ERCP) is an essential element in
      treating disease of the bilio-pancreatic system. In some patients, access to the
      bile ducts is limited due to operatively altered anatomy. The aim of this review
      is to illustrate the endoscopic procedure in these patients. We present the
      available evidence and comment on our approach to ERCP in patients with surgical
      modification of anatomy. In conclusion, conventional side-viewing or forward
      viewing endoscopes allow one to access the biliary system in most patients with
      Billroth-II or partial pancreaticoduodenectomy. By use of balloon enteroscopy,
      biliary intervention in spite of surgical reconstruction with a long limb - such
      as Roux-en-Y gastrojejunostomy or hepaticojejunostomy and gastric bypass for
      obesity - has become feasible in many cases. Adaption of accessory devices to
      balloon-assisted enteroscopes permits therapeutic interventions in these
      patients.

PMID- 20687022
TI  - [First standard chemotherapy for cholangiocellular carcinoma].

PMID- 20687023
TI  - [Irritable bowel syndrome: to scope or not to scope?].

PMID- 20687024
TI  - The US Army Public Health Command initiative: transforming public health services
      for the army.

PMID- 20687025
TI  - Entomological terrorism: a tactic in assymmetrical warfare.
AB  - The current operational environment presents military forces with enemies that
      use unconventional warfare to achieve their goals. Although the US government has
      dedicated significant resources to address threats of bioterrorism, the adaptive
      nature of our adversaries necessitates additional emphasis on bioterrorism
      awareness amongst military health professionals. This article provides an
      overview of three categories of entomological terrorism and examples from each
      category with a risk assessment.

PMID- 20687026
TI  - Issues related to burn pits in deployed settings.

PMID- 20687027
TI  - Using geographic information systems to maximize environmental surveillance
      efforts and impact.
AB  - There has been tremendous advancement in geographic information systems (GIS)
      software and hardware over the last 2 decades. This article illustrates how these
      advancements can be used to greatly increase the ease and efficiency of
      collecting environmental samples and demonstrate how environmental data collected
      within a GIS is more valuable because of the visualization, analysis, and
      historical capabilities of GIS. This article reviews 6 actual field surveys
      conducted using desktop GIS and field GIS by entomologists with the US Army
      Public Health Command (Provisional). While these examples entail entomological
      data, the techniques and procedures are applicable to any type of environmental
      data.

PMID- 20687028
TI  - Mystery of the x-ray overexposure: an innovative risk and media communication
      mentoring workshop.

PMID- 20687029
TI  - The impact of peer-based training on reducing radiation doses from x-ray
      operations in an interventional pain management clinic.
AB  - The purpose of this paper is to describe the measurement and characterization of
      the radiation exposure to the staff, patients, and the general public as a result
      of the operation of an interventional pain management (IPM) clinic, as well as
      the effectiveness of a peer-based fluoroscopy training program to keep doses as
      low as reasonably achievable (ALARA). During the last decade, pain management has
      evolved into an essential part of patient care. IPM, a subfield of pain
      management, uses fluoroscopic imaging in its procedures. As a result, there are 3
      separate populations who could possibly receive exposure to ionizing radiation as
      a result of an IPM radiographic procedure: staff, patients, and the general
      public. Staff doses, as well as doses to the general public, are easily measured
      with radiation dosimetry. Conversely, it is very difficult to characterize the
      radiation dose to a patient during a fluoroscopic procedure and realistically it
      is not possible to measure patient dose directly. However, it is plausible to
      infer relative patient exposure from direct measurement of the physician s dose.
      The most common and practical way to measure the dose to members of the general
      public is to monitor the ambient radiation levels within a medical treatment
      facility and extrapolate these measurements to the general public. Ultimately,
      the goal is to maintain all doses (patient, physician, and the general public)
      using the ALARA principle. Using a Panasonic thermoluminescent dosimetry system,
      it was determined that a peer-based fluoroscopy training program effectively
      reduced the cumulative dose to clinic staff by approximately 50 percent. It was
      also determined that the standard building materials used in our facility provide
      enough shielding to keep doses to members of the general public below acceptable
      limits.

PMID- 20687030
TI  - Resiliency training for medical professionals.
AB  - For the past 10 years, the military medical system costs have increased by an
      estimated 167 percent. Behavioral health issues and physical ailments are major
      contributors to the increased costs. As a result, fatigue and burnout of medical
      professionals are growing concerns. The Army Medical Department (AMEDD)
      recognizes that physical and psychological stressors adversely impact personal
      well-being and organizational goals. Thus, an emphasis on enhancing the
      individual s resiliency framework is essential to the stamina and long-term
      endurance to sustain the continued provision of high quality medical care. To
      that end, the Army Medical Command (MEDCOM) has instituted the Provider
      Resiliency Program. The Professional Provider Resiliency Training (PPRT)
      conducted by the AMEDD Center and School should be a key element of the MEDCOM
      Provider Resiliency Program. The PPRT provides medical professionals the
      opportunity to significantly develop and enhance their resiliency skills. This
      article includes outcome data from 172 medical professionals who attended the
      PPRT. Specific focus is on their perspective about resiliency training. The
      findings in this article revealed that the doctors (100 percent), nurses (98
      percent), behavioral health providers (90 percent) and other professionals (100
      percent) who attended the PPRT course valued the training and indicated that they
      will use the learned mind-body resiliency techniques.

PMID- 20687031
TI  - Observed noncompliance with implementation of vector-borne disease preventive
      measures among deployed forces.
AB  - Failure by individual service members and units to implement preventive measures
      to mitigate environmental health threats have always resulted in reduced
      efficiency of the Warfighter, with the attendant reduction in combat capability.
      This article describes observations at 2 sites in northern Iraq from July 2007 to
      September 2009 of deficiencies in the use of preventive and protective measures
      to reduce incidences of vector-borne diseases. Observations included individual
      service member s indifference or negative attitude toward use of personal
      protective equipment and unit leaders failure to provide required resources and
      enforce use of personal protective measures. Implications of these actions and
      recommendation for enhancing compliance are discussed.

PMID- 20687032
TI  - Evolution of the army hearing program in a deployed environment.

PMID- 20687033
TI  - Battling body fat.

PMID- 20687034
TI  - Aguardiente at the Alamo: alcohol abuse and the Texas war for independence, 1835
      1836.

PMID- 20687035
TI  - [Interventions and their effects on informal caregivers of people with dementia:
      a systematic literature review].
AB  - In home-care situations, the caring family members of people suffering from
      dementia are exposed to a great number of physical, mental and social burdens,
      and restrictions, putting themselves at risk of falling ill. Caring family
      members need adequate forms of relief in order to be able to care for the family
      member at home for as long as possible, and with the best possible physical and
      psychological status. In the present paper, interventions of relief and promotion
      and their effects on family members caring for dementia patients have been
      investigated and described on the basis of a systematic literature review. The
      presentation of the results shows that psycho-educational, relieving, supportive,
      psychotherapeutic and multimodal offers as well as counselling and case/care
      management among caring family members have significant effects on parameters
      such as burdens, level of depression, subjective well-being, skills/knowledge as
      well as symptoms and institutionalisation of the person in need of care. None of
      the interventions investigated, however, covers the entire range of parameters.
      In order to be able to ensure the individual support of caring family members, a
      superordinate organisational concept (case/care management, family health
      nursing) which meets the needs of the caring family members, combines and
      interlinks tailor-made offers for caring family members is required. Registered
      nurses could play a central role as care managers or family health nurses in
      ensuring home-based care for people with dementia. Further investigations on
      multimodal offers and case/care management are needed. In this context, it is
      essential to take well-considered decisions on study design, sample size, and
      result parameters (assessment instruments) in order to gain significant results
      and homogeneous data.

PMID- 20687036
TI  - [Autonomy in the nursing home--conceptual considerations regarding self
      determination and capacity to act on the basis of a model].
AB  - Autonomy is an exceptionally complex philosophical concept which is present in
      ethical considerations in health care settings. Currently, no consistent
      definition of autonomy exists. From the perspective of the authors, self
      determination and capacity to act independently are essential aspects of
      autonomy. While there are limited general results regarding autonomy in old age,
      autonomy of nursing home residents and the corresponding critical influence
      factors still lack in-depth examination. The aim of this article is to contribute
      to a more thorough understanding of autonomy of nursing home residents. Due to
      the high percentage of residents with cognitive impairment, this population plays
      a crucial role regarding the conceptualisation of autonomy. Various approaches
      combined with the perspectives developed by the interdisciplinary PAiN-Project
      team (Pain and Autonomy in the Nursing Home), led to the formulation of a novel
      conceptualisation of autonomy. Based on theoretical and discursive
      considerations, the model "Determination Factors of Autonomy" focuses on the
      residents' self-determination and ability to perform activities of daily living
      in the nursing home context. According to the author's conceptualisation,
      autonomy occurs in various ranges in regard to self-awareness as well as the
      appreciation of autonomy by others.

PMID- 20687037
TI  - [Perceptions and interpretations of nurse-patient interactions--a qualitative
      study].
AB  - This study analyses the interaction between nurses and paraplegic patients who
      are indicative of chronically ill persons in their pursuit of self-determination
      and autonomy, concerning all aspects of life. The study aims at closing a gap in
      the research about nurse-patient interaction. Data were collected in two German
      hospitals. We used problem-focussed interviews with nurses and patients, and
      participant observation at three points of time during the process of
      mobilisation. Data were analysed by hermeneutic case-reconstruction. The focus of
      analysis was on themes that were important for patients while receiving care and
      on how nurses perceive and interpret these themes. In several steps of analysis
      the categories were derived from the data, then the corresponding ones were
      linked together in order to establish key categories. This allowed identifying
      themes of concern for patients during the nursing process. In the next step, the
      patients' perspective was contrasted with the nurses' perspective. Central themes
      identified by this comparison were finally documented in a case description.
      Results show that communication during the nursing process and active
      participation are of central concern for patients.

PMID- 20687038
TI  - [Shaping the interaction between nurses and patients in the rehabilitation
      process--the example of hospital care for paraplegic persons].
AB  - This study analyses the interaction between nurses and paraplegic patients. The
      way how nurses perceived, interpreted and dealt with important themes for
      patients during the process of care determines the quality of interaction. Based
      on these findings we developed a model for interaction in the nursing process
      that is characterised by its orientation towards a mutual understanding. This
      model enables nurses to systematise nursing negotiation processes, from
      identifying problems to determining options for interventions to decision-making.

PMID- 20687039
TI  - ["Who is glossary?"--Focus-group evaluation of an evidence-based consumer
      information brochure on risk of falling and fall prevention in the elderly].
AB  - Evidence-based patient and consumer health information (EBPI) implies unbiased
      presentation of the scientific evidence aimed at consumers' informed decision
      making. A number of consumer information brochures on fall prevention in the
      elderly have been developed. However, none of these fulfil the criteria of EBPI.
      It is almost unknown how elderly people respond to EBPI. We performed three focus
      group interviews including 19 senior citizens to explore the comprehensibility
      and acceptance of an EBPI on risk of falling and fall prevention strategies. The
      analysis of the interviews revealed that the majority of participants did not
      understand the aim of the brochure, although it was explicitly stated. Most of
      them had expected concrete instructions on fall-risk management. The numerical
      and graphical figures and tables displaying fall-risk factors, fall and fracture
      incidence, and efficacy of the interventions were predominantly judged as
      confusing and unfamiliar. Beside negative emotional reactions, devaluation, and
      selective information seeking, a relevant number of participants also appreciated
      the objective and non-indoctrinating character of the EBPI. Our investigation
      confirms limited acceptance of EBPI which might predominately be caused by
      unsatisfied expectations and unfamiliarity with this kind of information.

PMID- 20687040
TI  - [Smoking history worldwide--cigarette smoking, passive smoking and smoke free
      environment in Switzerland].
AB  - After the invention of the cigarette 1881 the health consequences of active
      smoking were fully known only in 1964. Since 1986 research findings allow
      increasingly stronger conclusions about the impact of passive smoking on health,
      especially for lung cancer, cardiovascular and respiratory disease in adults and
      children and the sudden infant death syndrome. On the basis of current
      consumption patterns, approximately 450 million adults will be killed by smoking
      between 2000 and 2050. At least half of these adults will die between age 30 and
      69. Cancer and total deaths due to smoking have fallen so far only in men in high
      income countries but will rise globally unless current smokers stop smoking
      before or during middle age. Higher taxes, regulations on smoking, including 100
      % smoke free indoor spaces, and information for consumers could avoid smoking
      associated deaths. Irland was 2004 the first country worldwide introducing smoke
      free bars and restaurants with positive effects on compliance, health of
      employees and business. In the first year after the introduction these policies
      have resulted in a 10 - 20 % reduction of acute coronary events. In Switzerland
      smoke free regulations have been accepted by popular vote first in the canton of
      Ticino in 2006 and since then in 15 more cantons. The smoking rate dropped from
      33 to 27 % since 2001.

PMID- 20687041
TI  - [Why do not all smokers stop smoking?].
AB  - In spite of knowing the dangers of smoking, most smokers do not stop smoking
      timely before the development of smoking-related disease. The reasons why they do
      not consider stopping are multiple. The expectations and fears of the smokers
      must be known to the family doctor so that he or she can offer an individualized
      counseling.

PMID- 20687042
TI  - [The management of patients with nicotine dependence - the role of the general
      practitioners].
AB  - The gatekeeper needs a disease management of his patients who smoke.
      Questionnaires will help to define the diagnosis and grade of nicotine dependence
      as well as the fingerprint of the patients smoking career. The ICD-10 Code and
      the Fagerstrom Nicotine Dependence Test are used. There is no therapy indicated
      without the optimal motivation of the patient. The transtheoretical model of
      Prochaska and DiClemente ist widely accepted to separate the stadium of
      motivation into precontemplation, contemplation, preparation and action. Many
      other factors like earlier experiences, catastrophe scenaries, self-efficacy and
      selection of therapeutic modality are important for the best outcome. 90 % of the
      work of a gatekeeper is minimal intervention. This means individually tailored
      argumentations to shift the motivation of the patient to smoking cessation. The
      concept is defined in the rules of the five R's with relevance, risks, rewards,
      roadblocks and repetition. Following these criterias, the gatekeeper gets a
      positive shift of his motivation in up to 60 % with only one minimal
      intervention. The smoking cessation guidelines through the world are very similar
      and show a level A grade for a synergy of behavioural therapy and medication by
      either nicotine replacement, bupropion or vareniclin. The selection of any other
      regimen is either less efficient or anecdotally and leads to a further loss of
      life expectancy of the smoker. The gatekeeper has the infrastructure, the know
      how and the confidence of his patient to act as disease manager. A successful
      therapy is possible over six months with about seven consultations, the success
      rate is expected to be even higher than the values in the medication studies.
      Smokers should be informed by the health organizations to avoid self therapies
      and look for specialists help. The gatekeeper is an ideal candidate.

PMID- 20687043
TI  - [Smoking cessation training for physicians and other health professionals in
      Switzerland].
AB  - Almost one third of the Swiss population smokes. Of these persons a large
      percentage would like to quit smoking each year. It is well known that the odds
      to quit successfully are improved by professional counseling and medication
      support. In order to counsel the numerous smokers interested in quitting a
      sufficient number of professionals needs to be trained in smoking cessation. For
      this training a short and extended course in smoking cessation for physicians is
      available (Frei von Tabak project). For non-physician health professionals there
      is a postgraduate course in tobacco prevention and smoking cessation and for both
      groups of professionals there is the Hospital QuitSupport workshop, which aims to
      support and promote hospital-based smoking cessation counseling. Smoking
      cessation counseling by physicians is remunerated in the outpatient setting. For
      non-physician smoking cessation counselling, however, there is no such tarif for
      remuneration. This drawback presents a considerable obstacle for the
      establishment of a large-scale smoking cessation counseling network in
      Switzerland.

PMID- 20687044
TI  - [Motivating discussions, change of attitude and handling with stress - nursing
      aspects of smoking cessation].
AB  - Smoking cessation is a hard process. Encouragement and assistance are necessary!
      As a specialist for smoking cessation, you have to provide a good advisory
      service. That means, you have to solve the expected problems and to give the
      patient useful tips so he can spend this painful time with success. It is
      important to motivate the patient again and again, to give him a concept helping
      to change his habits and be able to cope with this stressful situation.

PMID- 20687046
TI  - [Cannabis and the lung - chill or kill?].
AB  - Cannabis is the most widely consumed illicit drug in the western world. Cannabis
      and tobacco smoke contain a similar mix of irritant and toxic chemicals.
      Therefore, there are reasons to suspect, that cannabis and tobacco have similar
      side effects. However, the pulmonary effects of smoking cannabis have not been
      extensively researched and the few findings are contradictory. Among the reasons
      for this uncertainty are its illegal status and the common practice of combining
      cannabis with tobacco. Separating the effects of the two substances is therefore
      difficult.

PMID- 20687045
TI  - [Medical therapy for smoking cessation].
AB  - Tobacco smoking is the leading cause of preventable morbidity and premature
      death. Physicians are in the unique position to promote smoking cessation and to
      support patients in quitting smoking is a key task for every single health care
      provider. Counselling smoking cessation is clearly shown to be both efficient and
      cost-effective in terms of years of live saved. Nicotine is highly addictive and
      to achieve long-term abstinence pharmacotherapy is frequently inevitable.
      Nicotine replacement therapy is efficacious and doubles the odds of permanently
      abstain from smoking. Further, strong evidence supports the use of buproprion, an
      atypical antidepressive agent, for quit smoking. Varenicline is the first
      medication specifically developed for smoking cessation. Varenicline is a partial
      agonist and antagonist at the nicotinic receptor that reduces craving, withdrawal
      symptoms and the reinforcing effect of smoking. This review summarises the
      current clinical data on the pharmacotherapy for smoking cessation and provides
      practical advice for daily clinical practice.

PMID- 20687047
TI  - [Preventive relapse treatment for tobacco cessation - is it worthwhile?].
AB  - Though different treatment modalities currently exist for tobacco cessation, many
      smokers still relapse following an initially successful quitting attempt. We
      herein provide a selected overview of tobacco relapse prevention strategies
      evaluated in different trials and in a recent meta-analysis. Most studies were
      characterised by an inadequate study design and insufficient numbers of
      participants. Randomised studies, both in selected (hospitalisation, pregnancy,
      military conscripts) and in unselected smoker groups showed no advantage of
      psychological interventions, mainly behavioural skills-based approaches. This was
      independent of whether smokers had been enrolled prior or after quitting tobacco.
      Pharmacological trials identified no benefit of preventive interventions with
      nicotine replacement treatments or Bupropion, but one study with prolonged
      Varenicline treatment significantly reduced the rate of relapse. Currently there
      is insufficient evidence to recommend systematic preventive relapse treatment for
      tobacco addiction with psychological or pharmacological interventions. Extended
      treatment with Varenicline may reduce relapse rates following tobacco cessation.
      Further meticulously designed and appropriately powered trials will be necessary
      to clarify the role of alternative psychological and pharmacological strategies
      for the prevention of relapse after tobacco cessation.

PMID- 20687049
TI  - Dermal fibroblast behaviour on micropatterned substrates with different pattern
      geometries.
AB  - A major objective of scaffold fabrication for tissue-engineering applications in
      wound healing is to understand the relationship between scaffold topography and
      cell behaviour. Recently, researchers have focused on arrays of cell adhesion
      protein styled in linear-grid micropatterns; however, these linear-grid patterns
      hardly reflect the topographical features of a natural extracellular matrix
      (ECM). In order to clarify the relationship between substrate adhesion points and
      cell behaviour, changes of dermal fibroblasts cultured on triangular microdot
      arrays were investigated. Micropatterns were micro-printed by silicone substrate
      stamps with collagen, while regions outside of the microdots were functionalized
      to block cellular adhesion. Cell morphology, expression of alpha-SMA, cell
      viability and hydroxyproline levels were examined for dermal fibroblasts cultured
      on the microdot substrates and on non-patterned control substrates. On patterned
      substrates, the expression of alpha-SMA significantly decreased, cell vitality
      increased and hydroxyproline content decreased with increasing vertex angles of
      the triangular array. Significantly more hydroxyproline was observed in all
      experimental groups in comparison to the control group. The results indicate that
      small vertex angles of the triangular array were detrimental to cell survival,
      likely due to constraint of the cell to a small adhesion area. We hypothesize
      that cells actively adapt to this situation by attempting to remodel their
      microenvironments with secretion of hydroxyproline. This illustrates the
      existence of feedback between cells and their microenvironments, such that when
      surroundings are unfavourably altered, the cells attempt to reconstruct the
      environment with secretion of ECM.

PMID- 20687048
TI  - Identifying targets to improve treatment in type 2 diabetes; the Groningen
      Initiative to aNalyse Type 2 diabetes Treatment (GIANTT) observational study.
AB  - PURPOSE: Assessment of quality of cardiometabolic risk management in diabetes in
      primary care. METHODS: In a descriptive cohort study including 95 Dutch general
      practices, we assessed medication treatment in relation to the level of control
      for HbA1c, systolic blood pressure (SBP) and LDL-cholesterol (LDL-c) in 2007. We
      also applied a prospective measure of treatment quality by assessing treatment
      modifications in not well-controlled patients. In a subpopulation of 23
      practices, we studied trends in these quality indicators from 2004 (2059
      patients) to 2007 (2929 patients). RESULTS: In 2007, averages for HbA1c, SBP and
      LDL-c were 6.9%, 142 mmHg and 2.3 mmol/l, respectively. Of the patients with an
      HbA1c >  8.5%, 16% were treated with one oral drug class and 50% used insulin. In
      27% of these patients, therapy modification occurred subsequently. During the 4
      year period, a slight decrease in average HbA1c was observed, but no changes in
      treatment level. In 2007, 56% of the patients had an SBP >= 140 mmHg, 19% of whom
      were not using antihypertensives. In the 13% with an SBP > 160 mmHg, 23% received
      a therapy modification. During the 4-year period, the average SBP decreased with
      6 mmHg but the treatment level showed no substantial increase. In 2007, 39% had
      an LDL-c level >= 2.5 mmol/l, 49% of whom were not using statins. Of the patients
      with an LDL-c > 3.5 mmol/l, only 9% received a therapy modification. CONCLUSIONS:
      The decreasing population averages of HbA1c, SBP and LDL-c values suggest
      improvement in quality of care. However, the relatively few therapy modifications
      observed in insufficiently controlled patients show room for improvement.

PMID- 20687050
TI  - Robotic-assisted minimally invasive surgery; a useful tool in resident training-
      the Peoria experience, 2002-2009.
AB  - BACKGROUND: The purpose of this study was to review the use of robotic-assisted
      general surgery at our institution. We evaluated the 8 year experience of one
      minimally invasive surgery (MIS) fellowship-trained surgeon in Peoria, IL,
      performing 240 cases of foregut, colon, solid organ and biliary surgery using the
      da Vinci system, with resident assistance. Foregut and colon procedures are the
      fifth and sixth most commonly performed procedures of the senior author annually.
      METHODS: An IRB-approved retrospective review of prospectively collected data
      representing 124 foregut and 102 colon operations was performed. Data analysed
      were procedure performed and indications for surgery, gender, age, body mass
      index (BMI), estimated blood loss (EBL), port set-up time (PST), robot operating
      time (ROT), total case time (TCT), length of stay (LOS), complications,
      conversions and resident involvement were recorded. Fourteen cases were excluded
      from the data review. Statistical analysis using the ANOVA test was applied. A
      specific review of resident participation was performed. RESULTS: Times for 226
      foregut and colon cases were: PST 31.2 +/- 9.4 (range 10-64) min, ROT 119.3 +/-
      41.5 (range 12-306) min, and TCT 194.8 +/- 50.3 (range 50-380) min. The EBL was
      48.6 +/- 55.0 (range 5-500) ml, BMI 28.5 +/- 4.7 (range 15.4-46.8) kg/m(2) , and
      median LOS 2.0 (range 0-27) days. The overall complication rate was 13.3%. No
      deaths occurred. Over the 8 year study period the number of cases participated in
      by residents was 0, 16, 22, 15, 29, 26, 28 and 10 (as of June 2009),
      respectively. CONCLUSION: This series demonstrates the technical feasibility and
      safety of robotic surgery for the foregut and colon in a clinical setting where
      the surgeon does far more of other types of MIS. This series compares favorably
      with the literature. Incorporation of robotic training in the curriculum has
      allowed residents to learn robotic techniques in an effective manner.

PMID- 20687051
TI  - The effects of burial on drug detection in skeletal tissues.
AB  - Skeletal tissues have recently been investigated for use in post-mortem
      toxicology. Variables affecting drug concentration in these tissues, however, are
      still poorly characterized. In this work, the relative effects of burial on the
      response of enzyme-linked immunosorbent assay (ELISA) and gas chromatography-mass
      spectrometry (GC-MS) assays were examined. Rats were acutely exposed to ketamine
      or diazepam, euthanized and buried outdoors. After one month, the remains were
      exhumed and skeletal tissue drug levels were compared those of non-buried rats. A
      climate-controlled burial was also undertaken using defleshed bones to
      approximate an extended decomposition. Long bones (femora, tibiae) were isolated
      and separated into tissue type (diaphyseal bone, epiphyseal bone, and marrow),
      and according to treatment (i.e. buried or non-buried). Following methanolic
      extraction (bone) or simple homogenization (marrow), samples were analyzed with
      ELISA. Samples were then pooled according to treatment, extracted by solid phase
      extraction (SPE) and confirmed with GC-MS. Under the conditions examined, the
      effects of burial appear to be drug and tissue dependent. Ketamine-exposed
      tissues demonstrated the greatest differences, especially in bone marrow. In
      diazepam-exposed tissues, burial did not seem to greatly affect drug response and
      some gave greater assay response compared to the non-buried set. Overall, the
      data suggest that fresh tissue samples may not be representative of decomposed
      samples in terms of skeletal tissue drug levels.

PMID- 20687052
TI  - Precision control of cellular pathways with light.

PMID- 20687053
TI  - The immobility of CO(2) in marine sediments beneath 1500 meters of water.
AB  - Injecting liquid CO(2) into deep-sea sediments below ca. 3 km of seawater has
      been suggested for the permanent storage of anthropogenic CO(2). At the pressures
      and temperature found below 3 km of seawater, CO(2) becomes denser than seawater
      and so is likely to remain permanently sequestered in the sediment. Deepwater
      engineering, however, is expensive and seawater depths of greater than 3 km are
      often only reached far from shore. Here, we consider the less expensive
      alternative of injecting CO(2) into marine sediments at depths shallower than
      required for denser-than-seawater CO(2) storage. We compare the mobility of
      liquid CO(2) that has been injected into deep-sea reservoirs with the mobility of
      supercritical CO(2) that has been injected into geologically equivalent (i.e.,
      identical porosity, permeability, and effective stress) reservoirs with
      terrestrial pressure and temperature conditions. We demonstrate that buoyant
      liquid CO(2) with a density of about 90 % that of seawater is sufficiently
      immobile that it can be considered trapped by gravity and capillarity. In
      contrast, supercritical CO(2) under typical terrestrial conditions is highly
      mobile and only trapped by the appropriate confining layer in either a structural
      or stratigraphic trap. As a result of its very high mobility under terrestrial
      conditions, CO(2) injected in an unconfined formation would spread beneath the
      confining layer to produce a large flat cylindrical-shaped plume of pure-phase
      CO(2). In contrast, the less mobile CO(2) in a typical deep-sea reservoir
      produces a spherical-shaped plume, resulting in a pure-phase-CO(2) footprint that
      is much smaller than the pure-phase-CO(2) footprint formed in the confined
      terrestrial reservoir.

PMID- 20687054
TI  - Single-stage production of highly concentrated hydrogen from biomass-derived
      syngas.

PMID- 20687055
TI  - Luminescent carbon nanodots: emergent nanolights.
AB  - Similar to its popular older cousins the fullerene, the carbon nanotube, and
      graphene, the latest form of nanocarbon, the carbon nanodot, is inspiring
      intensive research efforts in its own right. These surface-passivated
      carbonaceous quantum dots, so-called C-dots, combine several favorable attributes
      of traditional semiconductor-based quantum dots (namely, size- and wavelength
      dependent luminescence emission, resistance to photobleaching, ease of
      bioconjugation) without incurring the burden of intrinsic toxicity or elemental
      scarcity and without the need for stringent, intricate, tedious, costly, or
      inefficient preparation steps. C-dots can be produced inexpensively and on a
      large scale (frequently using a one-step pathway and potentially from biomass
      waste-derived sources) by many approaches, ranging from simple candle burning to
      in situ dehydration reactions to laser ablation methods. In this Review, we
      summarize recent advances in the synthesis and characterization of C-dots. We
      also speculate on their future and discuss potential developments for their use
      in energy conversion/storage, bioimaging, drug delivery, sensors, diagnostics,
      and composites.

PMID- 20687056
TI  - Nanometer-range communication of stereochemical information by reversible
      switching of molecular helicity.

PMID- 20687057
TI  - Gold(I)-catalyzed addition of diphenyl phosphate to alkynes: isomerization of
      kinetic enol phosphates to the thermodynamically favored isomers.

PMID- 20687058
TI  - Highly efficient mesoscopic dye-sensitized solar cells based on donor-acceptor
      substituted porphyrins.

PMID- 20687059
TI  - 1,2,3-trisubstituted indanes by highly diastereoselective palladium-catalyzed
      oxyarylation of indenes with arylboronic acids and nitroxides.

PMID- 20687060
TI  - Biomimetic photocycloaddition of 3-hydroxyflavones: synthesis and evaluation of
      rocaglate derivatives as inhibitors of eukaryotic translation.

PMID- 20687061
TI  - Large pore gels to separate mega protein complexes larger than 10 MDa by blue
      native electrophoresis: isolation of putative respiratory strings or patches.
AB  - Here, we expand the application of blue native electrophoresis to the separation
      of mega protein complexes larger than 10 MDa by introducing novel large pore
      acrylamide gels. We tailored the bis-acrylamide cross-linker amounts relative to
      the acrylamide monomer to enlarge the pore size of acrylamide gels and to obtain
      elastic and sufficiently stable gels. The novel gel types were then used to
      search for suprastructures of mitochondrial respiratory supercomplexes, the
      hypothetical respiratory strings, or patches. We identified 4-8 MDa assemblies
      that contain respiratory complexes I, III, and IV and most likely represent
      dimers, trimers, and tetramers of respiratory supercomplexes. We also isolated
      multimeric respiratory supercomplexes with apparent masses of 35-45 MDa, the
      presumed core pieces of respiratory strings or patches. Electron microscopic
      investigations will be required to clarify whether the isolated assemblies of
      complexes are ordered and specific, as predicted for respiratory strings and
      patches in the mitochondrial membrane.

PMID- 20687062
TI  - Vaccines for preventing cholera: killed whole cell or other subunit vaccines
      (injected).
AB  - BACKGROUND: Injected cholera vaccines are rarely used today, although they may
      have some benefit. It is valuable to summarize the evidence for effectiveness of
      injected cholera vaccines for comparison with newer oral vaccines (subject of a
      separate Cochrane Review). OBJECTIVES: To evaluate killed whole cell (KWC)
      cholera vaccines and other inactive subunit vaccines (administered by injection)
      for preventing cholera and death, and to evaluate the adverse effects. SEARCH
      STRATEGY: In September 2008, we searched the Cochrane Infectious Diseases Group
      Specialized Register, CENTRAL (The Cochrane Library 2008, Issue 3), EMBASE, and
      LILACS. We also searched reference lists and handsearched the journal Vaccine up
      to 1997. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials
      comparing injected cholera vaccines (KWC or other inactive subunit) with placebo,
      control vaccines, or no intervention in adults and children irrespective of
      immune status or special risk category. DATA COLLECTION AND ANALYSIS: Two authors
      extracted data and assessed trial methodological quality independently.
      Dichotomous data were reported using the risk ratio (RR) with 95% confidence
      intervals (CI). Vaccine efficacies were also calculated (% vaccine efficacy = (1
      RR) x 100%). MAIN RESULTS: Sixteen trials, involving over one million adults,
      children and infants, fulfilled the inclusion criteria. Twenty-four comparisons
      reported on vaccine efficacy (cholera cases and/or deaths) and 11 comparisons
      considered adverse effects (nine reported on both). Compared to placebo,
      vaccinees had a reduced risk of death from cholera (RR 0.49, 95% CI 0.25 to 0.93;
      837,442 participants) and a reduced risk of contracting cholera at 12 months (RR
      0.52, 95% CI 0.42 to 0.65, random-effects model; 1,512,573 participants). This
      translates to an efficacy of 48%, 95% confidence interval 35% to 58%. Significant
      protection lasted for two years, even after only a single dose, and for three
      years with an annual booster. Children over five years and adults were protected
      for up to three years, while children under five years were protected for up to a
      year. Injected cholera vaccines were associated with more systemic and local
      adverse effects compared to placebo, but these were not severe or life
      threatening. AUTHORS' CONCLUSIONS: Injected cholera vaccines appear to be safe
      and relatively more effective than usually realized. Protection against cholera
      persists for up to two years following a single dose of vaccine, and for three
      years with an annual booster. However, they have been superseded by oral
      vaccines.

PMID- 20687063
TI  - Antibiotics for preterm rupture of membranes.
AB  - BACKGROUND: Premature birth carries substantial neonatal morbidity and mortality.
      Subclinical infection is associated with preterm rupture of membranes (PROM).
      Prophylactic maternal antibiotic therapy might lessen infectious morbidity and
      delay labour, but could suppress labour without treating underlying infection.
      OBJECTIVES: To evaluate the immediate and long-term effects of administering
      antibiotics to women with PROM before 37 weeks, on maternal infectious morbidity,
      neonatal morbidity and mortality, and longer-term childhood development. SEARCH
      STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials
      Register (29 April 2010). SELECTION CRITERIA: Randomised controlled trials
      comparing antibiotic administration with placebo that reported clinically
      relevant outcomes were included as were trials of different antibiotics. Trials
      in which no placebo was used were included for the outcome of perinatal death
      alone. DATA COLLECTION AND ANALYSIS: We extracted data from each report without
      blinding of either the results or the treatments that women received. We sought
      unpublished data from a number of authors. MAIN RESULTS: We included 22 trials,
      involving 6800 women and babies.The use of antibiotics following PROM is
      associated with statistically significant reductions in chorioamnionitis (average
      risk ratio (RR) 0.66, 95% confidence interval (CI) 0.46 to 0.96, and a reduction
      in the numbers of babies born within 48 hours (average RR 0.71, 95% CI 0.58 to
      0.87) and seven days of randomisation (average RR 0.79, 95% CI 0.71 to 0.89). The
      following markers of neonatal morbidity were reduced: neonatal infection (RR
      0.67, 95% CI 0.52 to 0.85), use of surfactant (RR 0.83, 95% CI 0.72 to 0.96),
      oxygen therapy (RR 0.88, 95% CI 0.81 to 0.96), and abnormal cerebral ultrasound
      scan prior to discharge from hospital (RR 0.81, 95% CI 0.68 to 0.98). Co
      amoxiclav was associated with an increased risk of neonatal necrotising
      enterocolitis (RR 4.72, 95% CI 1.57 to 14.23).One study evaluated the children's
      health at seven years of age (ORACLE Children Study) and found antibiotics seemed
      to have little effect on the health of children. AUTHORS' CONCLUSIONS: The
      decision to prescribe antibiotics for women with PROM is not clearcut. Benefits
      in some short-term outcomes (prolongation of pregnancy, infection, less abnormal
      cerebral ultrasound before discharge from hospital) should be balanced against a
      lack of evidence of benefit for others, including perinatal mortality, and longer
      term outcomes. If antibiotics are prescribed it is unclear which would be the
      antibiotic of choice.Co-amoxiclav should be avoided in women at risk of preterm
      delivery due to increased risk of neonatal necrotising enterocolitis.

PMID- 20687064
TI  - Calcium supplementation during pregnancy for preventing hypertensive disorders
      and related problems.
AB  - BACKGROUND: Pre-eclampsia and eclampsia are common causes of serious morbidity
      and death. Calcium supplementation may reduce the risk of pre-eclampsia through a
      number of mechanisms, and may help to prevent preterm birth. OBJECTIVES: To
      assess the effects of calcium supplementation during pregnancy on hypertensive
      disorders of pregnancy and related maternal and child outcomes. SEARCH STRATEGY:
      We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (May
      2010) and contacted study authors. SELECTION CRITERIA: Randomised trials
      comparing at least 1 g daily of calcium during pregnancy with placebo. DATA
      COLLECTION AND ANALYSIS: We assessed eligibility and trial quality, extracted and
      double-entered data. MAIN RESULTS: We included 13 studies of good quality
      (involving 15,730 women). The average risk of high blood pressure was reduced
      with calcium supplementation rather than placebo (12 trials, 15,470 women: risk
      ratio (RR) 0.65, 95% confidence interval (CI) 0.53 to 0.81). There was also a
      reduction in the average risk of pre-eclampsia associated with calcium
      supplementation (13 trials, 15,730 women: RR 0.45, 95% CI 0.31 to 0.65). The
      effect was greatest for high-risk women (five trials, 587 women: RR 0.22, 95% CI
      0.12 to 0.42), and those with low baseline calcium intake (eight trials, 10,678
      women: RR 0.36, 95% CI 0.20 to 0.65).The average risk of preterm birth was
      reduced in the calcium group overall (11 trials, 15,275 women: RR 0.76, 95% CI
      0.60 to 0.97) and amongst women at high risk of developing pre-eclampsia
      recruited to four small trials (568 women: RR 0.45, 95% CI 0.24 to 0.83).There
      was no overall effect on the risk of stillbirth or death before discharge from
      hospital (11 trials 15,665 babies; RR 0.90, 95% CI 0.74 to 1.09). The composite
      outcome maternal death or serious morbidity was reduced (four trials, 9732 women;
      RR 0.80, 95% CI 0.65 to 0.97). Most of the women in these trials were low risk
      and had a low calcium diet. Maternal deaths were reported in only one trial. One
      death occurred in the calcium group and six in the placebo group, a difference
      which was not statistically significant (RR 0.17, 95% CI 0.02 to 1.39).Blood
      pressure in childhood has been assessed in two studies, only one of which is
      currently included: childhood systolic blood pressure greater than 95th
      percentile was reduced (514 children: RR 0.59, 95% CI 0.39 to 0.91). AUTHORS'
      CONCLUSIONS: Calcium supplementation appears to approximately halve the risk of
      pre-eclampsia, to reduce the risk of preterm birth and to reduce the rare
      occurrence of the composite outcome 'death or serious morbidity'. There were no
      other clear benefits, or harms.

PMID- 20687065
TI  - Injection allergen immunotherapy for asthma.
AB  - BACKGROUND: Allergen specific immunotherapy has long been a controversial
      treatment for asthma. Although beneficial effects upon clinically relevant
      outcomes have been demonstrated in randomised controlled trials, there remains a
      risk of severe and sometimes fatal anaphylaxis. The recommendations of
      professional bodies have ranged from cautious acceptance to outright dismissal.
      With increasing interest in new allergen preparations and methods of delivery, we
      updated the systematic review of allergen specific immunotherapy for asthma.
      OBJECTIVES: The objective of this review was to assess the effects of allergen
      specific immunotherapy for asthma. SEARCH STRATEGY: We searched the Cochrane
      Airways Group Trials Register up to 2005, Dissertation Abstracts and Current
      Contents. SELECTION CRITERIA: Randomised controlled trials using various forms of
      allergen specific immunotherapy to treat asthma and reporting at least one
      clinical outcome. DATA COLLECTION AND ANALYSIS: Three authors independently
      assessed eligibility of studies for inclusion. Two authors independently
      performed quality assessment of studies. MAIN RESULTS: Eighty-eight trials were
      included (13 new trials). There were 42 trials of immunotherapy for house mite
      allergy; 27 pollen allergy trials; 10 animal dander allergy trials; two
      Cladosporium mould allergy, two latex and six trials looking at multiple
      allergens. Concealment of allocation was assessed as clearly adequate in only 16
      of these trials. Significant heterogeneity was present in a number of
      comparisons. Overall, there was a significant reduction in asthma symptoms and
      medication, and improvement in bronchial hyper-reactivity following
      immunotherapy. There was a significant improvement in asthma symptom scores
      (standardised mean difference -0.59, 95% confidence interval -0.83 to -0.35) and
      it would have been necessary to treat three patients (95% CI 3 to 5) with
      immunotherapy to avoid one deterioration in asthma symptoms. Overall it would
      have been necessary to treat four patients (95% CI 3 to 6) with immunotherapy to
      avoid one requiring increased medication. Allergen immunotherapy significantly
      reduced allergen specific bronchial hyper-reactivity, with some reduction in non
      specific bronchial hyper-reactivity as well. There was no consistent effect on
      lung function. If 16 patients were treated with immunotherapy, one would be
      expected to develop a local adverse reaction. If nine patients were treated with
      immunotherapy, one would be expected to develop a systemic reaction (of any
      severity). AUTHORS' CONCLUSIONS: Immunotherapy reduces asthma symptoms and use of
      asthma medications and improves bronchial hyper-reactivity. One trial found that
      the size of the benefit is possibly comparable to inhaled steroids. The
      possibility of local or systemic adverse effects (such as anaphylaxis) must be
      considered.

PMID- 20687066
TI  - Fetal and umbilical Doppler ultrasound in normal pregnancy.
AB  - BACKGROUND: One of the main aims of routine antenatal care is to identify the 'at
      risk' fetus in order to apply clinical interventions which could result in
      reduced perinatal morbidity and mortality. Doppler ultrasound study of umbilical
      artery waveforms helps to identify the compromised fetus in 'high-risk'
      pregnancies and, therefore, deserves assessment as a screening test in 'low-risk'
      pregnancies. OBJECTIVES: To assess the effects on obstetric practice and
      pregnancy outcome of routine fetal and umbilical Doppler ultrasound in unselected
      and low-risk pregnancies. SEARCH STRATEGY: We searched the Cochrane Pregnancy and
      Childbirth Group Trials Register (May 2010). SELECTION CRITERIA: Randomised and
      quasi-randomised controlled trials of Doppler ultrasound for the investigation of
      umbilical and fetal vessels waveforms in unselected pregnancies compared to no
      Doppler ultrasound. Studies where uterine vessels have been assessed together
      with fetal and umbilical vessels have been included. DATA COLLECTION AND
      ANALYSIS: Two authors independently assessed the studies for inclusion, assessed
      risk of bias and carried out data extraction. MAIN RESULTS: We included five
      trials involving 14,185 women. The methodological quality of the trials was
      generally unclear because of insufficient data included in the reports.Routine
      fetal and umbilical Doppler ultrasound examination in low-risk or unselected
      populations did not result in increased antenatal, obstetric and neonatal
      interventions, and no overall differences were detected for substantive short
      term clinical outcomes such as perinatal mortality. There is no available
      evidence to assess the effect on substantive long term outcomes such as childhood
      neurodevelopment and no data to assess maternal outcomes, particularly
      psychological effects. AUTHORS' CONCLUSIONS: Existing evidence does not provide
      conclusive evidence that the use of routine umbilical artery Doppler ultrasound,
      or combination of umbilical and uterine artery Doppler ultrasound in low-risk or
      unselected populations benefits either mother or baby. Future studies should be
      designed to address small changes in perinatal outcome, and should focus on
      potentially preventable deaths.

PMID- 20687067
TI  - Tyrosine supplementation for phenylketonuria.
AB  - BACKGROUND: Phenylketonuria is an inherited disease for which the main treatment
      is the dietary restriction of the amino acid phenylalanine. The diet has to be
      initiated in the neonatal period to prevent or reduce mental handicap. However,
      the diet is very restrictive and unpalatable and can be difficult to follow. A
      deficiency of the amino acid tyrosine has been suggested as a cause of some of
      the neuropsychological problems exhibited in phenylketonuria. Therefore, this
      review aims to assess the efficacy of tyrosine supplementation for
      phenylketonuria. OBJECTIVES: To assess the effects of tyrosine supplementation
      alongside or instead of a phenylalanine-restricted diet for people with
      phenylketonuria, who commenced on diet at diagnosis and either continued on the
      diet or relaxed the diet later in life. To assess the evidence that tyrosine
      supplementation alongside, or instead of a phenylalanine-restricted diet improves
      intelligence, neuropsychological performance, growth and nutritional status,
      mortality rate and quality of life. SEARCH STRATEGY: We searched the Cochrane
      Cystic Fibrosis and Genetic Disorders Group's Trials Register which is comprised
      of references identified from comprehensive electronic database searches,
      handsearches of relevant journals and abstract books of conference proceedings.
      Additional studies were identified from handsearches of the Journal of Inherited
      Metabolic Disease (from inception in 1978 to 1998). The manufacturers of
      prescribable dietary products used in the treatment of phenylketonuria were also
      contacted for further references.Date of the most recent search of the Group's
      Inborn Errors of Metabolism Trials Register: 09 June 2010. SELECTION CRITERIA:
      All randomised or quasi-randomised trials investigating the use of tyrosine
      supplementation versus placebo in people with phenylketonuria in addition to, or
      instead of, a phenylalanine-restricted diet. People treated for maternal
      phenylketonuria were excluded. DATA COLLECTION AND ANALYSIS: Two authors
      independently assessed the trial eligibility, methodological quality and
      extracted the data. MAIN RESULTS: Six trials were found, of which three trials
      reporting the results of a total of 56 participants, were suitable for inclusion
      in the review. The blood tyrosine concentrations were significantly higher in the
      participants receiving tyrosine supplements than those in the placebo group, mean
      difference 23.46 (95% confidence interval 12.87 to 34.05). No significant
      differences were found between any of the other outcomes measured. AUTHORS'
      CONCLUSIONS: From the available evidence no recommendations can be made about
      whether tyrosine supplementation should be introduced into routine clinical
      practice. Further randomised controlled studies are required to provide more
      evidence.

PMID- 20687068
TI  - Aerobic exercise interventions for adults living with HIV/AIDS.
AB  - BACKGROUND: Access to combination antiretroviral therapy has turned HIV into a
      chronic and manageable disease for many. This increased chronicity has been
      mirrored by increased prevalence of health-related challenges experienced by
      people living with HIV (Rusch 2004). Exercise is a key strategy for people living
      with HIV and by rehabilitation professionals to address these disablements;
      however, knowledge about the effects of exercise among adults living with HIV
      still is emerging. OBJECTIVES: To examine the safety and effectiveness of aerobic
      exercise interventions on immunologic and virologic, cardiopulmonary, psychologic
      outcomes and strength, weight, and body composition in adults living with HIV.
      SEARCH STRATEGY: Searches of MEDLINE, EMBASE, SCIENCE CITATION INDEX, CINAHL,
      HEALTHSTAR, PsycINFO, SPORTDISCUS and Cochrane Review Group Databases were
      conducted between 1980 and June 2009. Searches of published and unpublished
      abstracts and proceedings from major international and national HIV/AIDS
      conferences were conducted, as well as a handsearch of reference lists and tables
      of contents of relevant journals and books. SELECTION CRITERIA: We included
      studies of randomised controlled trials (RCTs) comparing aerobic exercise
      interventions with no aerobic exercise interventions or another exercise or
      treatment modality, performed at least three times per week for at least four
      weeks among adults (18 years of age or older) living with HIV. DATA COLLECTION
      AND ANALYSIS: Data on study design, participants, interventions, outcomes, and
      methodological quality were abstracted from included studies by two reviewers.
      Meta-analyses, using RevMan 5 computer software, were performed on outcomes when
      possible. MAIN RESULTS: A total of 14 studies met inclusion criteria for this
      review and 30 meta-analyses over several updates were performed. Main results
      indicated that performing constant or interval aerobic exercise, or a combination
      of constant aerobic exercise and progressive resistive exercise for at least 20
      minutes at least three times per week for at least five weeks appears to be safe
      and may lead to significant improvements in selected outcomes of cardiopulmonary
      fitness (maximum oxygen consumption), body composition (leg muscle area, percent
      body fat), and psychological status (depression-dejection symptoms). These
      findings are limited to participants who continued to exercise and for whom there
      were adequate follow-up data. AUTHORS' CONCLUSIONS: Aerobic exercise appears to
      be safe and may be beneficial for adults living with HIV. These findings are
      limited by the small sample sizes and large withdrawal rates described in the
      studies. Future research would benefit from participant follow-up and intention
      to-treat analysis. Further research is required to determine the optimal
      parameters in which aerobic exercise may be most beneficial for adults living
      with HIV.

PMID- 20687069
TI  - Physical methods for preventing deep vein thrombosis in stroke.
AB  - BACKGROUND: Deep vein thrombosis (DVT) and resulting pulmonary embolism (PE) are
      important complications of stroke. Physical methods to reduce the risk of DVT and
      PE, such as graduated compression stockings (GCS) or intermittent pneumatic
      compression (IPC) applied to the legs, do not appear to be associated with any
      bleeding risk and reduce the risk of DVT in some categories of surgical patients.
      We sought to assess their effects in stroke patients. OBJECTIVES: To assess the
      effectiveness and safety of physical methods of reducing the risk of DVT, fatal
      or non-fatal PE and death in patients with recent stroke. SEARCH STRATEGY: We
      searched the Cochrane Stroke Group Trials Register (last searched November 2009),
      the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane
      Library Issue 4, 2009), MEDLINE (1966 to November 2009), EMBASE (1980 to November
      2009), CINAHL (1982 to November 2009) and The British Nursing Index (1985 to
      November 2009). We screened reference lists of all relevant papers, searched
      ongoing trials registers (November 2009) and contacted experts in the field.
      SELECTION CRITERIA: Unconfounded randomised controlled trials comparing physical
      methods for reducing the risk of DVT with control and in which prophylaxis was
      started within seven days of the onset of stroke. DATA COLLECTION AND ANALYSIS:
      Two review authors searched for trials and extracted data. MAIN RESULTS: We
      identified two trials of GCS that included 2615 patients and two small studies of
      IPC that included 177 patients. Overall, physical methods were not associated
      with a significant reduction in DVTs during the treatment period (odds ratio (OR)
      0.85, 95% confidence interval (CI) 0.70 to 1.04) or deaths (OR 1.12, 95% CI 0.87
      to 1.45). Use of GCS was not associated with any significant reduction in risk of
      DVT (OR 0.88, 95% CI 0.72 to 1.08) or death (OR 1.13, 95% CI 0.87 to 1.47) at the
      end of follow up. IPC was associated with a non-significant trend towards a lower
      risk of DVTs (OR 0.45, 95% CI 0.19 to 1.10) with no evidence of an effect on
      deaths (OR 1.04, 95% CI 0.37 to 2.89). AUTHORS' CONCLUSIONS: Evidence from
      randomised trials does not support the routine use of GCS to reduce the risk of
      DVT after acute stroke. There is insufficient evidence to support the routine use
      of IPC to reduce the risk of DVT in acute stroke and further larger randomised
      studies of IPC are needed to reliably assess the balance of risks and benefits of
      this intervention.

PMID- 20687070
TI  - Interventions for treating oral mucositis for patients with cancer receiving
      treatment.
AB  - BACKGROUND: Treatment of cancer is increasingly effective but associated with
      short and long term side effects. Oral side effects, including oral mucositis
      (mouth ulceration), remain a major source of illness despite the use of a variety
      of agents to treat them. OBJECTIVES: To assess the effectiveness of interventions
      for treating oral mucositis or its associated pain in patients with cancer
      receiving chemotherapy or radiotherapy or both. SEARCH STRATEGY: Electronic
      searches of Cochrane Oral Health Group and PaPaS Trials Registers (to 1 June
      2010), CENTRAL via The Cochrane Library (to Issue 2, 2010), MEDLINE via OVID
      (1950 to 1 June 2010), EMBASE via OVID (1980 to 1 June 2010), CINAHL via EBSCO
      (1980 to 1 June 2010), CANCERLIT via PubMed (1950 to 1 June 2010), OpenSIGLE
      (1980 to 1 June 2010) and LILACS via the Virtual Health Library (1980 to 1 June
      2010) were undertaken. Reference lists from relevant articles were searched and
      the authors of eligible trials were contacted to identify trials and obtain
      additional information. SELECTION CRITERIA: All randomised controlled trials
      comparing agents prescribed to treat oral mucositis in people receiving
      chemotherapy or radiotherapy or both. Outcomes were oral mucositis, time to heal
      mucositis, oral pain, duration of pain control, dysphagia, systemic infection,
      amount of analgesia, length of hospitalisation, cost and quality of life. DATA
      COLLECTION AND ANALYSIS: Data were independently extracted, in duplicate, by two
      review authors. Authors were contacted for details of randomisation, blindness
      and withdrawals. Risk of bias assessment was carried out on six domains. The
      Cochrane Collaboration statistical guidelines were followed and risk ratio (RR)
      values calculated using fixed-effect models (less than 3 trials in each meta
      analysis). MAIN RESULTS: Thirty-two trials involving 1505 patients satisfied the
      inclusion criteria. Three comparisons for mucositis treatment including two or
      more trials were: benzydamine HCl versus placebo, sucralfate versus placebo and
      low level laser versus sham procedure. Only the low level laser showed a
      reduction in severe mucositis when compared with the sham procedure, RR 5.28 (95%
      confidence interval (CI) 2.30 to 12.13).Only 3 comparisons included more than one
      trial for pain control: patient controlled analgesia (PCA) compared to the
      continuous infusion method, therapist versus control, cognitive behaviour therapy
      versus control. There was no evidence of a difference in mean pain score between
      PCA and continuous infusion, however, less opiate was used per hour for PCA, mean
      difference 0.65 mg/hour (95% CI 0.09 to 1.20), and the duration of pain was less
      1.9 days (95% CI 0.3 to 3.5). AUTHORS' CONCLUSIONS: There is weak and unreliable
      evidence that low level laser treatment reduces the severity of the mucositis.
      Less opiate is used for PCA versus continuous infusion. Further, well designed,
      placebo or no treatment controlled trials assessing the effectiveness of
      interventions investigated in this review and new interventions for treating
      mucositis are needed.

PMID- 20687071
TI  - Acupuncture for Bell's palsy.
AB  - BACKGROUND: Bell's palsy or idiopathic facial palsy is an acute facial paralysis
      due to inflammation of the facial nerve. A number of studies published in China
      have suggested acupuncture is beneficial for facial palsy. OBJECTIVES: The
      objective of this review was to examine the efficacy of acupuncture in hastening
      recovery and reducing long-term morbidity from Bell's palsy. SEARCH STRATEGY: We
      updated the searches of the Cochrane Neuromuscular Disease Group Trials
      Specialized Register (24 May 2010), The Cochrane Central Register of Controlled
      Trials (CENTRAL) (Issue 2, 2010), MEDLINE (January 1966 to May 2010), EMBASE
      (January 1980 to May 2010), AMED (January 1985 to May 2010), LILACS (from January
      1982 to May 2010) and the Chinese Biomedical Retrieval System (January 1978 to
      May 2010) for randomised controlled trials using 'Bell's palsy' and its synonyms,
      'idiopathic facial paralysis' or 'facial palsy' as well as search terms including
      'acupuncture'. Chinese journals in which we thought we might find randomised
      controlled trials relevant to our study were handsearched. We reviewed the
      bibliographies of the randomised trials and contacted the authors and known
      experts in the field to identify additional published or unpublished data.
      SELECTION CRITERIA: We included all randomised controlled trials involving
      acupuncture by needle insertion in the treatment of Bell's palsy irrespective of
      any language restrictions. DATA COLLECTION AND ANALYSIS: Two review authors
      identified potential articles from the literature search, extracted data and
      assessed quality of each trial independently. All disagreements were resolved by
      discussion between the review authors. MAIN RESULTS: The literature search and
      handsearching identified 49 potentially relevant articles. Of these, six RCTs
      were included involving 537 participants with Bell's palsy. Two more possible
      trials were identified in the update than the previous version of this systematic
      review, but both were excluded because they were not real RCTs. Of the six
      included trials, five used acupuncture while the other one used acupuncture
      combined with drugs. No trial reported on the outcomes specified for this review.
      Harmful side effects were not reported in any of the trials. Poor quality caused
      by flaws in study design or reporting (including uncertain method of
      randomisation, allocation concealment and blinding) and clinical differences
      between trials prevented reliable conclusions about the efficacy of acupuncture.
      AUTHORS' CONCLUSIONS: The quality of the included trials was inadequate to allow
      any conclusion about the efficacy of acupuncture. More research with high quality
      trials is needed.

PMID- 20687072
TI  - Interventions for replacing missing teeth: maintaining and recovering soft tissue
      health around dental implants.
AB  - BACKGROUND: It is important to institute an effective supportive therapy to
      maintain or recover soft tissue health around dental implants. Different
      maintenance regimens have been suggested, however it is unclear which are the
      most effective. OBJECTIVES: To assess the effects of different interventions for
      1) maintaining and 2) recovering soft tissue health around osseointegrated dental
      implants. SEARCH STRATEGY: We searched the Cochrane Oral Health Group's Trials
      Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE
      and EMBASE. Handsearching included several dental journals. We checked the
      bibliographies of the identified randomised controlled trials (RCTs) and relevant
      review articles for studies outside the handsearched journals. We wrote to
      authors of all identified RCTs, to more than 55 oral implant manufacturers and to
      an Internet discussion group to find unpublished or ongoing RCTs. No language
      restrictions were applied. The last electronic search was conducted on 2 June
      2010. SELECTION CRITERIA: All randomised controlled trials comparing agents or
      interventions for maintaining or recovering healthy tissues around dental
      implants. DATA COLLECTION AND ANALYSIS: Screening of eligible studies, assessment
      of the methodological quality of the trials and data extraction were conducted in
      duplicate and independently by two review authors. Results were expressed as
      random-effects models using standardised mean differences for continuous data and
      risk ratios for dichotomous data with 95% confidence intervals. MAIN RESULTS:
      Five trials compared interventions for maintaining soft tissue health around
      implants and a further six trials compared interventions to recover soft tissue
      health where there was evidence of peri-implant mucositis. No statistically
      significant differences were found between the effectiveness of powered versus
      manual toothbrushes for either maintaining or recovering soft tissue health.
      There was no statistically significant difference found between different types
      of self administered antimicrobials for maintaining soft tissue health
      (hyaluronic acid gel compared to chlorhexidine gel, amine fluoride/stannous
      fluoride mouthwash compared to chlorhexidine mouthwash) and triclosan dentifrice
      compared to sodium fluoride dentifrice showed no statistically significant
      difference in recovering soft tissue health. However chlorhexidine irrigation was
      more effective in reducing plaque and marginal bleeding scores compared to
      chlorhexidine mouthwash and Listerine mouthwash was found to be statistically
      significantly better than placebo with regard to reducing mean plaque scores and
      marginal bleeding scores. When interventions administered by dental professional
      were compared there was no statistically significant difference found between
      chlorhexidine and physiologic solutions as irrigants at second stage surgery to
      maintain health of soft tissues. In patients with peri-implant mucositis two
      trials evaluated interventions performed by dental professionals. There was no
      statistically significant difference between mechanical debridement followed by
      either minocycline or chlorhexidine gel, or between debridement with a titanium
      curette compared to an ultrasonic debridement tool. AUTHORS' CONCLUSIONS: There
      was only low quality evidence for which are the most effective interventions for
      maintaining or recovering health of peri-implant soft tissues. The included RCTs
      had short follow-up periods and few subjects and although overall the risk of
      bias of the studies was either low or unclear, only single trials were available
      for each outcome. There was no reliable evidence as to which regimens are most
      effective for long term maintenance. This should not be interpreted as meaning
      that current maintenance regimens are ineffective. There was weak evidence that
      antibacterial mouthrinses are effective in reducing plaque and marginal bleeding
      around implants. More RCTs should be conducted in this area. In particular, there
      is a definite need for trials powered to find possible differences, using primary
      outcome measures and with much longer follow up. Such trials should be reported
      according to the CONSORT guidelines (www.consort-statement.org/).

PMID- 20687073
TI  - Heroin maintenance for chronic heroin-dependent individuals.
AB  - BACKGROUND: Several types of medications have been used for stabilizing heroin
      users: Methadone, Buprenorphine and levo-alpha-acetyl-methadol (LAAM.) The
      present review focuses on the prescription of heroin to heroin-dependent
      individuals. OBJECTIVES: To compare heroin maintenance to methadone or other
      substitution treatments for opioid dependence regarding: efficacy and
      acceptability, retaining patients in treatment, reducing the use of illicit
      substances, and improving health and social functioning. SEARCH STRATEGY: A
      review of the Cochrane Central Register of Trials (The Cochrane Library Issue 1,
      2005), MEDLINE (1966 to 2008), EMBASE (1980 to 2005) and CINAHL until 2005 (on
      OVID) was conducted. Personal communication with researchers in the field of
      heroin prescription identified other ongoing trials. SELECTION CRITERIA:
      Randomised controlled trials of heroin maintenance treatment (alone or combined
      with methadone) were compared with any other pharmacological treatment for heroin
      dependent individuals. DATA COLLECTION AND ANALYSIS: Two reviewers independently
      assessed trial quality and extracted data. MAIN RESULTS: Eight studies involving
      2007 patients were included. Results show marginal significance in favour of
      heroin for remaining in treatment until the end of the study (8 studies, N= 2007,
      RR=1.23, 95%CI=0.96-1.57; heterogeneity P < 0.01). Adverse events are
      significantly more frequent in the heroin group. Heroin plus methadone
      prescription for maintenance treatment in adult chronic opioid users who failed
      previous methadone treatment attempts decreases the use of other illicit
      substances (3 Studies, N=1289, RR=0.63, 95%CI=0.49, 0.81, heterogeneity P=0.21),
      and reduces the risk of being incarcerated (2 studies, N=1103, RR=0.64,
      95%CI=0.51-0.79, heterogeneity P=0.31). In addition, we also found a marginally
      significant protective effect of heroin prescription plus methadone for the use
      of street heroin (3 studies, N=1512, RR=0.70, 95%CI=0.49-1.00, heterogeneity P <
      0.01) and for criminal activity (4 studies, N=1377, RR=0.80, 95%CI=0.61-1.04,
      heterogeneity P=0.31). There was not enough power to detect statistically
      significant results for the risk of death (5 studies, N=1817, RR=0.77, 95%CI=0.32
      1.87, heterogeneity P=0.79). AUTHORS' CONCLUSIONS: The available evidence
      suggests a small added value of heroin prescribed alongside flexible doses of
      methadone for long-term, treatment-refractory opioid users, considering a
      decrease in the use of street heroin and other illicit substances, and in the
      probability of being imprisoned; and an increase in retention in treatment. Due
      to the higher rate of serious adverse events, heroin prescription should remain a
      treatment of last resort for people who are currently or have in the past failed
      maintenance treatment.

PMID- 20687074
TI  - Calcium channel blockers versus other classes of drugs for hypertension.
AB  - BACKGROUND: Calcium channel blockers (CCBs) are a relatively new antihypertensive
      class. The effect of first-line CCBs on the prevention of cardiovascular events,
      as compared with other antihypertensive drug classes, is unknown. OBJECTIVES: To
      determine whether CCBs used as first-line therapy for hypertension are different
      from other first-line drug classes in reducing the incidence of major adverse
      cardiovascular events. SEARCH STRATEGY: Electronic searches of the Cochrane
      Central Register of Controlled Trials, MEDLINE, EMBASEand the WHO-ISH
      Collaboration Register (up to May 2009) were performed. We also checked the
      references of published studies to identify additional trials. SELECTION
      CRITERIA: Randomized controlled trial (RCT) comparing first-line CCBs with other
      antihypertensive classes, with at least 100 randomized hypertensive participants
      and with a follow-up of at least two years. DATA COLLECTION AND ANALYSIS: Two
      authors independently selected the included trials, evaluated the risk of bias
      and entered the data for analysis. MAIN RESULTS: Eighteen RCTs (14
      dihydropyridines, 4 non-dihydropyridines) with a total of 141,807 participants
      were included. All-cause mortality was not different between first-line CCBs and
      any other first-line antihypertensive classes. CCBs reduced the following
      outcomes as compared to beta-blockers: total cardiovascular events (RR 0.84, 95%
      CI [0.77, 0.92]), stroke (RR 0.77, 95% CI [0.67, 0.88]) and cardiovascular
      mortality (RR 0.90, 95% CI [0.81, 0.99]). CCBs increased total cardiovascular
      events (RR 1.05 , 95% CI [1.00, 1.09], p = 0.03) and congestive heart failure
      events (RR 1.37, 95% CI [1.25, 1.51]) as compared to diuretics. CCBs reduced
      stroke (RR 0.89, 95% CI [0.80, 0.98]) as compared to ACE inhibitors and reduced
      stroke (RR 0.85, 95% CI [0.73, 0.99]) and MI (RR 0.83, 95% CI [0.72, 0.96]) as
      compared to ARBs. CCBs also increased congestive heart failure events as compared
      to ACE inhibitors (RR 1.16, 95% CI [1.06, 1.27]) and ARBs (RR 1.20, 95% CI [1.06,
      1.36]). The other evaluated outcomes were not significantly different. AUTHORS'
      CONCLUSIONS: Diuretics are preferred first-line over CCBs to optimize reduction
      of cardiovascular events. The review does not distinguish between CCBs, ACE
      inhibitors or ARBs, but does provide evidence supporting the use of CCBs over
      beta-blockers. Many of the differences found in the current review are not robust
      and further trials might change the conclusions. More well-designed RCTs studying
      the mortality and morbidity of patients taking CCBs as compared with other
      antihypertensive drug classes are needed for patients with different stages of
      hypertension, different ages, and with different co-morbidities such as diabetes.

PMID- 20687075
TI  - Noninvasive positive pressure ventilation as a weaning strategy for intubated
      adults with respiratory failure.
AB  - BACKGROUND: Noninvasive positive pressure ventilation (NPPV) provides ventilatory
      support without the need for an invasive airway approach. Interest has emerged in
      using NPPV to facilitate earlier removal of an endotracheal tube and decrease
      complications associated with prolonged intubation. OBJECTIVES: To summarize the
      evidence comparing NPPV and invasive positive pressure ventilation (IPPV) weaning
      on clinical outcomes in intubated adults with respiratory failure. SEARCH
      STRATEGY: We searched the Cochrane Central Register of Controlled Trials (The
      Cochrane Library, Issue 2, 2008), MEDLINE (January 1966 to April 2008), EMBASE
      (January 1980 to April 2008), proceedings from four conferences, and personal
      files; and contacted authors to identify randomized controlled trials comparing
      NPPV and IPPV weaning. SELECTION CRITERIA: Randomized and quasi-randomized
      studies comparing early extubation with immediate application of NPPV to IPPV
      weaning in intubated adults with respiratory failure. DATA COLLECTION AND
      ANALYSIS: Two review authors independently assessed trial quality and abstracted
      data according to prespecified criteria. Sensitivity and subgroup analyses were
      planned to assess the impact of (i) excluding quasi-randomized trials, and (ii)
      the etiology of respiratory failure on selected outcomes. MAIN RESULTS: We
      identified 12 trials of moderate to good quality that involved 530 participants
      with predominantly chronic obstructive pulmonary disease (COPD). Compared to the
      IPPV strategy, NPPV significantly decreased mortality (relative risk (RR) 0.55,
      95% confidence Interval (CI) 0.38 to 0.79), ventilator associated pneumonia (RR
      0.29, 95% CI 0.19 to 0.45), length of stay in an intensive care unit (weighted
      mean difference (WMD) -6.27 days, 95% CI -8.77 to -3.78) and hospital (WMD -7.19
      days, 95% CI -10.80 to -3.58), total duration of ventilation (WVD) -5.64 days
      (95% CI -9.50 to -1.77) and duration of endotracheal mechanical ventilation (WMD 
      7.81 days, 95% CI -11.31 to -4.31). Noninvasive weaning had no effect on weaning
      failures or the duration of ventilation related to weaning. Excluding a single
      quasi-randomized trial maintained the significant reduction in mortality and
      ventilator associated pneumonia. Subgroup analyses suggested that the benefits on
      mortality and weaning failures were nonsignificantly greater in trials enrolling
      exclusively COPD patients versus mixed populations. AUTHORS' CONCLUSIONS: Summary
      estimates from 12 small studies of moderate to good quality that included
      predominantly COPD patients demonstrated a consistent, positive effect on
      mortality and ventilator associated pneumonia. The net clinical benefits
      associated with noninvasive weaning remain to be fully elucidated.

PMID- 20687076
TI  - Recombinant Factor VIIa concentrate versus plasma derived concentrates for the
      treatment of acute bleeding episodes in people with haemophilia and inhibitors.
AB  - BACKGROUND: In people with haemophilia, therapeutic clotting agents might be
      recognised as a foreign protein and induce anti-FVIII antibodies, known as
      'inhibitors'. Drugs insensitive to such antibodies, either recombinant or plasma
      derived, are called factor VIII "by-passing" agents and used for treatment of
      bleeding in people with inhibitors. OBJECTIVES: To determine the clinical
      effectiveness of recombinant FVIIa concentrate in comparison to plasma-derived
      concentrates for the treatment of acute bleeding episodes in people with
      haemophilia and inhibitors. SEARCH STRATEGY: We searched the Cochrane Cystic
      Fibrosis and Genetic Disorders Group Coagulopathies Trials Register which
      comprises references identified from comprehensive electronic database searches
      and handsearches of relevant journals and abstract books of conference
      proceedings.Date of the most recent search of the Group's Trials Register: 07
      July 2010. SELECTION CRITERIA: Randomised (RCTs) and quasi-randomised controlled
      clinical trials comparing recombinant FVIIa concentrate (rFVIIa) to human plasma
      derived concentrates (high-dose human or recombinant FVIII or FIX concentrate;
      prothrombin complex concentrates (PCCs); activated prothrombin complex
      concentrate (aPCC)) in persons with haemophilia. Comparisons with animal derived
      products were excluded. DATA COLLECTION AND ANALYSIS: Two authors independently
      assessed trials (eligibility and risk of bias) and extracted data. No meta
      analysis was performed due to unavailability of outcomes and comparisons common
      to the included studies. MAIN RESULTS: A total of ten trials were identified, two
      of which (total of 69 participants) were eligible for analysis. Both trials
      showed methodological flaws and did not show superiority of one treatment over
      the other. Both the treatments showed that (rFVIIa and aPCC appeared to have a
      similar haemostatic effect in both studies, without increasing thromboembolic
      risk. AUTHORS' CONCLUSIONS: Although the main conclusion should be the need for
      further randomised controlled trials, we conclude that both rFVIIa and aPCC can
      be used to treat bleeding in haemophiliacs with inhibitors.

PMID- 20687077
TI  - Selective serotonin reuptake inhibitors (SSRIs) for autism spectrum disorders
      (ASD).
AB  - BACKGROUND: Autism spectrum disorders (ASD) are characterised by abnormalities in
      social interaction and communication skills, as well as stereotypic behaviours
      and restricted activities and interests. Selective serotonin reuptake inhibitors
      (SSRIs) are prescribed for the treatment of co-morbidity associated with ASD such
      as depression, anxiety and obsessive-compulsive behaviours. OBJECTIVES: To
      determine if treatment with an SSRI: 1. improves the core features of autism
      (social interaction, communication and behavioural problems); 2. improves other
      non-core aspects of behaviour or function such as self-injurious behaviour; 3.
      improves the quality of life of children and their carers; 4. has short and long
      term effects on outcome; 5. causes harms. SEARCH STRATEGY: We searched the
      Cochrane Central Register of Controlled Trials (The Cochrane Library 2009, Issue
      4), MEDLINE ( December 2009), EMBASE (December 2009), CINAHL (December 2009),
      PsycINFO (December 2009) and ERIC (December 2009), without language restrictions.
      SELECTION CRITERIA: Randomised controlled trials (RCTs) of any dose of oral SSRI
      compared with placebo, in participants with autism spectrum disorders. Trials
      must have included at least one standardised outcome measure. DATA COLLECTION AND
      ANALYSIS: Two authors independently selected and appraised studies for inclusion
      and risk of bias. All data were continuous. Meta-analysis, where possible, used a
      random-effects model. MAIN RESULTS: Seven RCTs with a total of 271 participants
      were included. Four SSRIs were evaluated: fluoxetine (two studies), fluvoxamine
      (two studies), fenfluramine (two studies) and citalopram (one study). Five
      studies included only children and two studies included only adults. Varying
      inclusion criteria were used with regard to diagnostic criteria and intelligence
      of participants. Seventeen different outcome measures were reported. Although
      more than one study reported data for Clinical Global Impression (CGI) and
      obsessive-compulsive behaviour (OCB), different tool types or components of these
      outcomes were used in each study. As such, data were unsuitable for meta
      analysis. One large, high quality study in children showed no evidence of
      positive effect of citalopram. Two small studies in adults showed positive
      outcomes for CGI and OCB; one study showed improvements in aggression and another
      in anxiety. AUTHORS' CONCLUSIONS: There is no evidence of effect of SSRIs in
      children and emerging evidence of harm. There is limited evidence of the
      effectiveness of SSRIs in adults from small studies in which risk of bias is
      unclear.

PMID- 20687078
TI  - Hydralazine for essential hypertension.
AB  - BACKGROUND: Hypertension is associated with an increased risk of stroke,
      myocardial infarction and congestive heart failure. Hydralazine is a direct
      acting vasodilator which has been used for the treatment of hypertension since
      the 1950's. Although it has largely been replaced by newer antihypertensive drugs
      with more acceptable tolerability profiles, hydralazine is still widely used in
      developing countries due to its lower cost. A review of its relative
      effectiveness compared to placebo on surrogate and clinical outcomes is
      justified. OBJECTIVES: To quantify the effect of hydralazine compared to placebo
      in randomized controlled trials (RCTs) on all cause mortality, cardiovascular
      mortality, serious adverse events, myocardial infarctions, strokes, withdrawals
      due to adverse effects and blood pressure in patients with primary hypertension.
      SEARCH STRATEGY: We searched the following databases: Cochrane Central Register
      of Controlled Trials (to Second Quarter 2009), MEDLINE (2005-June 2009),
      International Pharmaceutical Abstracts (1970-June 2009) and EMBASE (2007-June
      2009). Bibliographic citations from retrieved studies were also reviewed. No
      language restrictions were applied. SELECTION CRITERIA: We selected RCTs studying
      the effect of oral hydralazine compared to oral placebo in patients with primary
      hypertension. We excluded studies of patients with secondary hypertension or
      gestational hypertension. DATA COLLECTION AND ANALYSIS: Two reviewers
      independently extracted data and assessed trial quality using the risk of bias
      tool. Data synthesis and analysis was performed using RevMan 5. MAIN RESULTS: The
      search strategy did not yield any randomized controlled trials comparing
      hydralazine to placebo for inclusion in this review. There is insufficient
      evidence to conclude on the effects of hydralazine versus placebo on mortality,
      morbidity, withdrawals due to adverse effects, serious adverse events, or
      systolic and diastolic blood pressure. Some of the adverse effects related to
      hydralazine that have been reported in the literature include reflex tachycardia,
      hemolytic anemia, vasculitis, glomerulonephritis, and a lupus-like syndrome.
      AUTHORS' CONCLUSIONS: Hydralazine may reduce blood pressure when compared to
      placebo in patients with primary hypertension, however this data is based on
      before and after studies, not RCTs. Furthermore, its effect on clinical outcomes
      remains uncertain.

PMID- 20687079
TI  - Timing of prophylactic uterotonics for the third stage of labour after vaginal
      birth.
AB  - BACKGROUND: Administration of the uterotonic drugs is one of the main components
      of the active management of the third stage of labour. The timing of uterotonics
      varies considerably across the globe and it may have significant implications on
      the well-being of the mothers and their babies. OBJECTIVES: To assess the effect
      of the timing of administration of prophylactic uterotonics (before compared to
      after placental delivery) on the outcomes related to the third stage of labour.
      SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials
      Register (September 2009). SELECTION CRITERIA: Randomised controlled trials
      examining the timing of prophylactic uterotonic drugs in the third stage of
      labour. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the
      studies for inclusion, assessed risk of bias and carried out data extraction.
      Data entry was checked MAIN RESULTS: We included three trials involving 1671
      participants; oxytocin was the only uterotonic drug that was used. The dose and
      route of administration of oxytocin varied among the included studies.
      Administration of oxytocin before and after the expulsion of placenta does not
      significantly influence the incidence of postpartum haemorrhage (blood loss
      greater than 500 ml) (risk ratio (RR) 0.81, 95% confidence interval (CI) 0.62 to
      1.04; n = 1667, three trials); retained placenta (RR 1.54, 95% CI 0.76 to 3.11; n
      = 1667, three trials); length of third stage of labour (minutes) (mean difference
      (MD) -0.30, 95% CI -0.95 to 0.36; n = 1667, three trials); postpartum blood loss
      (ml) (MD 22.32, 95% CI -58.21 to 102.86; n = 181, two trials); changes in
      haemoglobin (g/dL) (MD 0.06, 95% CI -0.60 to 0.72; n = 51, one trial); blood
      transfusion (RR 0.79, 95% CI 0.23 to 2.73; n = 1667, three trials); the use of
      additional uterotonics (RR 1.10, 95% CI 0.80 to 1.52; n = 1667, three trials);
      the incidence of maternal hypotension (RR 2.48, 95% CI 0.23 to 26.70; n = 130,
      one trial) and the incidence of severe postpartum haemorrhage (blood loss 1000 ml
      or more) (RR 0.98, 95% CI 0.48 to 1.98; n = 130, one trial). No data on other
      maternal or neonatal outcome measures were available. AUTHORS' CONCLUSIONS:
      Administration of oxytocin before and after the expulsion of placenta did not
      have any significant influence on many clinically important outcomes such as the
      incidence of postpartum haemorrhage, rate of placental retention and the length
      of the third stage of labour. However, the number of available studies were
      limited. The only uterotonic drug used was oxytocin, mainly through intravenous
      infusion, therefore its extrapolation to other routes of administration should be
      interpreted cautiously. More studies are required to examine other maternal and
      neonatal outcomes using consistent approaches.

PMID- 20687080
TI  - Chemotherapy for second-stage Human African trypanosomiasis.
AB  - BACKGROUND: Human African trypanosomiasis, or sleeping sickness, is a painful and
      protracted disease affecting people in the poorest parts of Africa and is fatal
      without treatment. Few drugs are currently available for second-stage sleeping
      sickness, with considerable adverse events and variable efficacy. OBJECTIVES: To
      evaluate the effectiveness and safety of drugs for treating second-stage human
      African trypanosomiasis. SEARCH STRATEGY: We searched the Cochrane Infectious
      Diseases Group Specialized Register (May 2010), CENTRAL (The Cochrane Library
      Issue 3 2010) , MEDLINE (1966 to May 2010), EMBASE (1974 to May 2010), LILACS
      (1982 to May 2010 ), BIOSIS (1926-May 2010), mRCT (May 2010) and reference lists.
      We contacted researchers working in the field and organizations. SELECTION
      CRITERIA: Randomized and quasi-randomized controlled trials. DATA COLLECTION AND
      ANALYSIS: Two authors (VL and AK) extracted data and assessed methodological
      quality; a third author (JS) acted as an arbitrator. Included trials only
      reported dichotomous outcomes, and we present these as risk ratio (RR) with 95%
      confidence intervals (CI). MAIN RESULTS: Nine trials with 2577 participants, all
      with Trypansoma brucei gambiense HAT, were included. Seven trials tested
      currently available drugs: melarsoprol, eflornithine, nifurtimox, alone or in
      combination; one trial tested pentamidine, and one trial assessed the addition of
      prednisolone to melarsoprol. Fixed 10-day regimens of melarsoprol were found to
      be as effective as those of 26 days, with similar numbers of adverse events.
      Melarsoprol monotherapy gave fewer relapses than pentamidine or nifurtimox, but
      resulted in more adverse events.Later trials evaluate nifurtimox combined with
      eflornithine (NECT), showing this gives few relapses and is well tolerated. It
      also has practical advantages in reducing the burden on health personnel and
      patients, when compared to eflornithine monotherapy. AUTHORS' CONCLUSIONS: Choice
      of therapy for second stage Gambiense HAT will continue to be determined by what
      is locally available, but eflornithine and NECT are likely to replace
      melarsoprol, with careful parasite resistance monitoring. We need research on
      reducing adverse effects of currently used drugs, testing different regimens, and
      experimental and clinical studies of new compounds, effective for both stages of
      the disease.

PMID- 20687081
TI  - Antibiotic therapy for Shigella dysentery.
AB  - BACKGROUND: Shigella dysentery is a relatively common illness and occasionally
      causes death, worldwide. Mild symptoms are self-limiting but in more severe
      cases, antibiotics are recommended for cure and preventing relapse. The
      antibiotics recommended are diverse, have regional differences in sensitivity,
      and have side effects. OBJECTIVES: To evaluate the efficacy and safety of
      antibiotics for treating Shigella dysentery. SEARCH STRATEGY: In June 2009 we
      identified all relevant trials from the following databases: Cochrane Infectious
      Diseases Group Specialized Register; Cochrane Central Register of Controlled
      Trials (CENTRAL) (The Cochrane Library 2008, issue 4), MEDLINE, EMBASE, LILACS
      and the metaRegister of Controlled Trials (mRCT). We also checked conference
      proceedings for relevant abstracts, and contacted researchers, organizations, and
      pharmaceutical companies. SELECTION CRITERIA: Randomized controlled trials of
      antibiotics for Shigella dysentery. DATA COLLECTION AND ANALYSIS: Four authors,
      working in pairs, independently assessed trial eligibility, methodological
      quality, and extracted data. We calculated risk ratios (RR) with 95% confidence
      intervals (CI) for dichotomous data, and used the random-effects model for
      significant heterogeneity. We explored possible sources of heterogeneity, when
      present, in subgroup analyses of participant age and percentage of participants
      with confirmed Shigella infection. MAIN RESULTS: Sixteen trials (1748
      participants), spanning four decades and with differing sensitivity to Shigella
      isolates, met the inclusion criteria. Seven were judged to be at risk of bias due
      to inadequate allocation concealment or blinding, and 12 due to incomplete
      reporting of outcome data. Limited data from one three-armed trial of people with
      moderately severe illness suggest that antibiotics reduce the episodes of
      diarrhoea at follow-up (furazolidone versus no drug RR 0.21, 95% CI 0.09 to 0.48,
      73 participants; cotrimoxazole versus no drug RR 0.30, 95% CI 0.15 to 0.59, 76
      participants).There was insufficient evidence to consider any class of antibiotic
      superior in efficacy in treating Shigella dysentery, but heterogeneity for some
      comparisons limits confidence in the results. All the antibiotics studied were
      safe. There was inadequate evidence regarding the role of antibiotics in
      preventing relapses. AUTHORS' CONCLUSIONS: Antibiotics reduce the duration of
      Shigella dysentery.Regularly updated local or regional antibiotic sensitivity
      patterns to different species and strains of Shigella are required to guide
      empiric therapy. More trials adhering to standard guidelines are required to
      evaluate the role of antibiotics in the treatment of severe forms of Shigella
      dysentery and in groups who are at high risk of complications.

PMID- 20687082
TI  - Hypnosis for children undergoing dental treatment.
AB  - BACKGROUND: Managing children is a challenge that many dentists face. Many non
      pharmacological techniques have been developed to manage anxiety and behavioural
      problems in children, such us: 'tell, show & do', positive reinforcement,
      modelling and hypnosis. The use of hypnosis is generally an overlooked area,
      hence the need for this review. OBJECTIVES: This systematic review attempted to
      answer the question: What is the effectiveness of hypnosis (with or without
      sedation) for behaviour management of children who are receiving dental care in
      order to allow successful completion of treatment? NULL HYPOTHESIS: Hypnosis has
      no effect on the outcome of dental treatment of children. SEARCH STRATEGY: We
      searched the Cochrane Oral Health Group's Trials Register, CENTRAL, MEDLINE
      (OVID), EMBASE (OVID), and PsycINFO. Electronic and manual searches were
      performed using controlled vocabulary and free text terms with no language
      restrictions. Date of last search: 11th June 2010. SELECTION CRITERIA: All
      children and adolescents aged up to 16 years of age. Children having any dental
      treatment, such as: simple restorative treatment with or without local
      anaesthetic, simple extractions or management of dental trauma. DATA COLLECTION
      AND ANALYSIS: Information regarding methods, participants, interventions, outcome
      measures and results were independently extracted, in duplicate, by two review
      authors. Authors of trials were contacted for details of randomisation and
      withdrawals and a quality assessment was carried out. The methodological quality
      of randomised controlled trials (RCTs) was assessed using the criteria described
      in the Cochrane Handbook for Systematic Reviews of Interventions 5.0.2. MAIN
      RESULTS: Only three RCTs (with 69 participants) fulfilled the inclusion criteria.
      Statistical analysis and meta-analysis were not possible due to insufficient
      number of studies. AUTHORS' CONCLUSIONS: Although there are a considerable number
      of anecdotal accounts indicating the benefits of using hypnosis in paediatric
      dentistry, on the basis of the three studies meeting the inclusion criteria for
      this review there is not yet enough evidence to suggest its beneficial effects.

PMID- 20687083
TI  - Structured telephone support or telemonitoring programmes for patients with
      chronic heart failure.
AB  - BACKGROUND: Specialised disease management programmes for chronic heart failure
      (CHF) improve survival, quality of life and reduce healthcare utilisation. The
      overall efficacy of structured telephone support or telemonitoring as an
      individual component of a CHF disease management strategy remains inconclusive.
      OBJECTIVES: To review randomised controlled trials (RCTs) of structured telephone
      support or telemonitoring compared to standard practice for patients with CHF in
      order to quantify the effects of these interventions over and above usual care
      for these patients. SEARCH STRATEGY: Databases (the Cochrane Central Register of
      Controlled Trials (CENTRAL), Database of Abstracts of Reviews of Effects (DARE)
      and Health Technology Assessment Database (HTA) on The Cochrane Library, MEDLINE,
      EMBASE, CINAHL, AMED and Science Citation Index Expanded and Conference Citation
      Index on ISI Web of Knowledge) and various search engines were searched from 2006
      to November 2008 to update a previously published non-Cochrane review.
      Bibliographies of relevant studies and systematic reviews and abstract conference
      proceedings were handsearched. No language limits were applied. SELECTION
      CRITERIA: Only peer reviewed, published RCTs comparing structured telephone
      support or telemonitoring to usual care of CHF patients were included.
      Unpublished abstract data was included in sensitivity analyses. The intervention
      or usual care could not include a home visit or more than the usual (four to six
      weeks) clinic follow-up. DATA COLLECTION AND ANALYSIS: Data were presented as
      risk ratio (RR) with 95% confidence intervals (CI). Primary outcomes included all
      cause mortality, all-cause and CHF-related hospitalisations which were meta
      analysed using fixed effects models. Other outcomes included length of stay,
      quality of life, acceptability and cost and these were described and tabulated.
      MAIN RESULTS: Twenty-five studies and five published abstracts were included. Of
      the 25 full peer-reviewed studies meta-analysed, 16 evaluated structured
      telephone support (5613 participants), 11 evaluated telemonitoring (2710
      participants), and two tested both interventions (included in counts).
      Telemonitoring reduced all-cause mortality (RR 0.66, 95% CI 0.54 to 0.81, P <
      0.0001) with structured telephone support demonstrating a non-significant
      positive effect (RR 0.88, 95% CI 0.76 to 1.01, P = 0.08). Both structured
      telephone support (RR 0.77, 95% CI 0.68 to 0.87, P < 0.0001) and telemonitoring
      (RR 0.79, 95% CI 0.67 to 0.94, P = 0.008) reduced CHF-related hospitalisations.
      For both interventions, several studies improved quality of life, reduced
      healthcare costs and were acceptable to patients. Improvements in prescribing,
      patient knowledge and self-care, and New York Heart Association (NYHA) functional
      class were observed. AUTHORS' CONCLUSIONS: Structured telephone support and
      telemonitoring are effective in reducing the risk of all-cause mortality and CHF
      related hospitalisations in patients with CHF; they improve quality of life,
      reduce costs, and evidence-based prescribing.

PMID- 20687084
TI  - Interventions for preventing mastitis after childbirth.
AB  - BACKGROUND: Despite the health benefits of breastfeeding, initiation and duration
      rates continue to fall short of international guidelines. Many factors influence
      a woman's decision to wean; the main reason cited for weaning is associated with
      lactation complications, such as mastitis. OBJECTIVES: To assess the effects of
      preventive strategies for mastitis and the subsequent effect on breastfeeding
      duration. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth
      Group's Trials Register (November 2009), CENTRAL (The Cochrane Library 2009,
      Issue 4), MEDLINE (1950 to November 2009), EMBASE (1974 to November 2009), CINAHL
      (1981 to November 2009), MIDIRS (1971 to November 2009), IPA (1970 to November
      2009), AMED (1985 to November 2009) and LILACS (1982 to November 2009). SELECTION
      CRITERIA: We included randomised controlled trials of interventions for
      preventing mastitis in postpartum breastfeeding women. DATA COLLECTION AND
      ANALYSIS: We independently identified relevant studies and assessed the trial
      quality. We contacted trial authors for missing data and information as
      appropriate. MAIN RESULTS: We included five trials (involving 960 women). In
      three trials of 471 women, we found no significant differences in the incidence
      of mastitis between use of antibiotics and no antibiotics (risk ratio (RR) 0.43;
      95% confidence interval (CI) 0.11 to 1.61; or in one trial of 99 women comparing
      two doses (RR 0.38; 95% CI 0.02 to 9.18). We found no significant differences for
      mastitis in three trials of specialist breastfeeding education with usual care
      (one trial); anti-secretory factor cereal (one trial); and mupirocin, fusidic
      acid ointment or breastfeeding advice (one trial).Generally we found no
      differences in any of the trials for breastfeeding initiation or duration; or
      symptoms of mastitis. AUTHORS' CONCLUSIONS: There was insufficient evidence to
      show effectiveness of any of the interventions, including breastfeeding
      education, pharmacological treatments and alternative therapies, regarding the
      occurrence of mastitis or breastfeeding exclusivity and duration. While studies
      reported the incidence of mastitis, they all used different interventions.
      Caution needs to be applied when considering the findings of this review as the
      conclusion is based on studies, often with small sample sizes. An urgent need for
      further adequately powered research is needed into this area to conclusively
      determine the effectiveness of these interventions.

PMID- 20687085
TI  - Cervical preparation for second trimester dilation and evacuation.
AB  - BACKGROUND: Abortion during the second trimester of pregnancy accounts for 10-15%
      of abortions performed worldwide. Dilation and evacuation (D&E) is the preferred
      method of second-trimester abortion in most parts of the developed world.
      Cervical preparation is recommended for dilation and curettage (D&C) after 12
      weeks gestation and is standard practice for D&E beyond 14 weeks gestation.
      Prostaglandins, osmotic dilators, and Foley balloon catheters have been used and
      studied as cervical preparation prior to second-trimester D&E. However, no
      consensus exists as to which cervical preparation method is superior with regards
      to safety, procedure time, need for additional dilation, ability to perform the
      procedure, or patient and provider acceptability. Despite the fact that the
      advent of osmotic dilation has improved the safety of the D&E procedure during
      the second trimester, it is unclear whether a certain type of osmotic dilator is
      superior to another or whether osmotic dilation with adjuvant prostaglandin is
      superior to osmotic dilation alone or to prostaglandins alone. OBJECTIVES: This
      review evaluates cervical preparation methods for second-trimester surgical
      abortion with respect to differences in procedure time, dilation achieved, need
      for additional dilation, complications, ability to complete the procedure,
      patient pain scores, and patient and provider acceptability and satisfaction.
      SEARCH STRATEGY: We searched for trials of cervical preparation prior to second
      trimester D&E. SELECTION CRITERIA: We included all randomized controlled trials
      that compared osmotic, mechanical, antiprogesterone, prostaglandin, or other
      medical agents of cervical preparation for second-trimester surgical abortion
      from 14-24 weeks of gestation. DATA COLLECTION AND ANALYSIS: Data were abstracted
      by two authors and data entry was verified by a third author. Mean difference and
      Peto Odds Ratio were calculated. MAIN RESULTS: Osmotic dilators were found to be
      superior to prostaglandins with respect to cervical dilation throughout the
      second trimester and with respect to procedure time within the early second
      trimester. Addition of prostaglandins to osmotic dilators was not found to
      increase cervical dilation, except after 19 weeks gestation, however, no impact
      was seen on procedure time. Addition of Mifepristone to misoprostol was found to
      improve cervical dilation, yet increase procedure time and frequency of pre
      procedural expulsions. Two-day cervical preparation was found to produce greater
      cervical preparation than one-day, but had no impact on procedure time. Serious
      complication rates or ability to complete the procedure did not differ
      significantly between any of the preparation methods reviewed. AUTHORS'
      CONCLUSIONS: Cervical preparation with osmotic dilators and/or misoprostol before
      second-trimester D&E is safe and effective. Osmotic dilators appear to provide
      superior cervical dilation when compared to prostaglandins alone or when combined
      with prostaglandins, however this difference in cervical dilation does not appear
      to result in differences in procedure time or complication rates. There does not
      appear to be clear clinical benefit from two days of cervical preparation
      compared to one-day prior to second-trimester D&E below 19 weeks gestational
      duration. Mifepristone plus misoprostol was associated with high rates of pre
      procedural expulsions and does not appear to be a useful method of cervical
      preparation before second-trimester dilation and evacuation. Same-day procedures
      appear to be a safe and reasonable option in the early second trimester, however,
      more research is needed to assess the effectiveness and safety of same-day
      procedures in the later second trimester.

PMID- 20687086
TI  - Alternative magnesium sulphate regimens for women with pre-eclampsia and
      eclampsia.
AB  - BACKGROUND: Magnesium sulphate remains the drug of choice for both prevention and
      treatment of women with eclampsia. Regimens for administration of this drug have
      evolved over the years, but have not yet been formally evaluated. OBJECTIVES: To
      assess the comparative effects of alternative regimens for the administration of
      magnesium sulphate when used for the care of women with pre-eclampsia or
      eclampsia, or both. SEARCH STRATEGY: We searched the Cochrane Pregnancy and
      Childbirth Group's Trials Register (June 2010). SELECTION CRITERIA: Randomised
      trials comparing different regimens for administration of magnesium sulphate used
      for the care of women with pre-eclampsia or eclampsia, or both. DATA COLLECTION
      AND ANALYSIS: All four review authors assessed trial quality and extracted data
      independently. MAIN RESULTS: We identified 17 studies of which six (866 women)
      met the inclusion criteria: two trials (451 women) compared regimens for women
      with eclampsia and four (415 women) for women with pre-eclampsia.Treatment of
      eclampsia: one trial compared loading dose alone with loading dose plus
      maintenance therapy for 24 hours (401 women). There was no clear difference
      between the groups in the risk ratio (RR) of recurrence of convulsions (RR 1.13,
      95% confidence interval (CI) 0.42 to 3.05) or stillbirth (RR 1.13, 95% CI 0.66 to
      1.92), and the CIs are wide. One trial compared a low dose regimen with a
      standard dose regimen over 24 hours (50 women). This study was too small for any
      reliable conclusions about the comparative effects.Prevention of eclampsia: one
      trial compared intravenous with intramuscular maintenance regimen for 24 hours
      (17 women). This trial was too small for any reliable conclusions. Three trials
      compared short maintenance regimens postpartum with continuing for 24 hours after
      the birth (398 women), even taken together these trials were too small for any
      reliable conclusions. AUTHORS' CONCLUSIONS: Although strong evidence supports the
      use of magnesium sulphate for prevention and treatment of eclampsia, trials
      comparing alternative treatment regimens are too small for reliable conclusions.

PMID- 20687087
TI  - Surgical versus conservative interventions for treating acromioclavicular
      dislocation of the shoulder in adults.
AB  - BACKGROUND: Dislocation of the acromioclavicular joint is one of the most common
      shoulder problems in general orthopaedic practice. The question of whether
      surgery should be used remains controversial. OBJECTIVES: To assess the relative
      effects of surgical versus conservative (non-surgical) interventions for treating
      acromioclavicular dislocations in adults. SEARCH STRATEGY: We searched the
      Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (to February
      2009), the Cochrane Central Register of Controlled Trials (The Cochrane Library
      2009, Issue 1), MEDLINE (1966 to February 2009), EMBASE (1988 to February 2009),
      and LILACS (1982 to February 2009), trial registries and reference lists of
      articles. There were no restrictions based on language or publication status.
      SELECTION CRITERIA: All randomised and quasi-randomised trials that compared
      surgical with conservative treatment of acromioclavicular dislocation in adults
      were included. DATA COLLECTION AND ANALYSIS: All review authors independently
      performed study selection. Two authors independently assessed the included trials
      and performed data extraction. MAIN RESULTS: Three trials were included in this
      review. These involved a total of 174 mainly male participants. Two trials were
      randomised and one was quasi-randomised. None used validated measures for
      assessing functional outcome.Fixation of the acromioclavicular joint using
      coracoclavicular screws, acromioclavicular pins or, usually threaded, wires was
      compared with supporting the arm in a sling or similar device. There were no
      significant differences between the two groups in unsatisfactory longer-term (one
      year) shoulder function based on a composite measure including pain, movement and
      strength or function (risk ratio 1.49, 95% confidence interval 0.75 to 2.95), nor
      in treatment failure that generally required an operation (risk ratio 1.72, 95%
      confidence interval 0.72 to 4.12). However, there were fixation failures in all
      three trials. Particularly, the trial using wires reported a high incidence of
      wire breakage (16/39 (41%)). Two trials reported that surgery significantly
      delayed the return to work. The methods used in the three trials also meant a
      routine second operation for implant removal was necessary. AUTHORS' CONCLUSIONS:
      There is insufficient evidence from randomised controlled trials to determine
      when surgical treatment is indicated for acromioclavicular dislocation in adults
      in current practice. Sufficiently powered, good quality, well-reported randomised
      trials of currently-used surgical interventions versus conservative treatment for
      well-defined injuries are required.

PMID- 20687088
TI  - Deferasirox for managing transfusional iron overload in people with sickle cell
      disease.
AB  - BACKGROUND: Sickle cell disease (SCD) is a group of genetic haemoglobin
      disorders. Increasingly, some people with SCD develop secondary iron overload due
      to occasional red blood cell transfusions or are on long-term transfusion
      programmes for e.g. secondary stroke prevention. Iron chelation therapy can
      prevent long-term complications.Deferoxamine and deferiprone have been found to
      be efficacious. However, questions exist about the effectiveness and safety of
      the new oral chelator deferasirox. OBJECTIVES: To assess the effectiveness and
      safety of oral deferasirox in people with SCD and secondary iron overload. SEARCH
      STRATEGY: We searched the Cystic Fibrosis & Genetic Disorders Group's
      Haemoglobinopathies Trials Register (06 April 2010).We searched MEDLINE, EMBASE,
      EBMR, Biosis Previews, Web of Science, Derwent Drug File, XTOXLINE and three
      trial registries: www.controlled-trials.com; www.clinicaltrials.gov;
      www.who.int./ictrp/en/. Most recent searches: 22 June 2009. SELECTION CRITERIA:
      Randomised controlled trials comparing deferasirox with no therapy or placebo or
      with another iron chelating treatment schedule. DATA COLLECTION AND ANALYSIS: Two
      authors independently assessed study quality and extracted data. We contacted the
      study author for additional information. MAIN RESULTS: One study (203 people) was
      included comparing the efficacy and safety of deferasirox and deferoxamine after
      12 months. Data were not available on mortality or end-organ damage. Using a pre
      specified dosing algorithm serum ferritin reduction was similar in both groups,
      mean difference (MD) 375.00 microg/l in favour of deferoxamine; (95% confidence
      interval (CI) -106.08 to 856.08). Liver iron concentration measured by
      superconduction quantum interference device showed no difference for the overall
      group of patients adjusted for transfusion category, MD -0.20 mg Fe/g dry weight
      (95% CI -3.15 to 2.75).Mild stable increases in creatine were observed more often
      in people treated with deferasirox, risk ratio 1.64 (95% CI 0.98 to 2.74).
      Abdominal pain and diarrhoea occurred significantly more often in people treated
      with deferasirox. Rare adverse events (less than 5% increase) were not reported;
      long-term adverse events could not be measured in the included study (follow-up
      52 weeks). Patient satisfaction with, and convenience of treatment were
      significantly better with deferasirox. AUTHORS' CONCLUSIONS: Deferasirox appears
      to be as effective as deferoxamine. However, only limited evidence is available
      assessing the efficacy regarding patient-important outcomes. The short-term
      safety of deferasirox seems to be acceptable, however, follow-up was too short to
      exclude long-term side effects and thus treatment with deferasirox cannot be
      judged completely safe. Future studies should assess long-term outcomes for
      safety and efficacy, and also evaluate rarer adverse effects.

PMID- 20687089
TI  - Statins for the treatment of dementia.
AB  - BACKGROUND: The use of statin therapy in established Alzheimer's disease (AD) or
      vascular dementia (VaD) is a relatively unexplored area. In AD ss-amyloid protein
      (Ass) is deposited in the form of extracellular plaques and previous studies have
      determined Ass generation is cholesterol dependent. Hypercholesterolaemia has
      also been implicated in the pathogenesis of VaD. Due to the role of statins in
      cholesterol reduction it is biologically plausible they may be efficacious in the
      treatment of AD and dementia. OBJECTIVES: To assess the clinical efficacy and
      tolerability of statins in the treatment of dementia. SEARCH STRATEGY: We
      searched the Specialized Register of the Cochrane Dementia and Cognitive
      Improvement Group, The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL and
      LILACS, as well as many trials registries and grey literature sources (27 October
      2008). SELECTION CRITERIA: Double-blind, randomized controlled trials of statins
      given for at least six months in people with a diagnosis of dementia. DATA
      COLLECTION AND ANALYSIS: Two independent authors extracted and assessed data
      independently against the inclusion criteria. Data were pooled where appropriate
      and entered into a meta-analysis. MAIN RESULTS: Three studies were identified
      (748 participants, age range 50-90 years). All patients had a diagnosis of
      probable or possible AD according to standard criteria and most patients were
      established on a cholinesterase inhibitor. Treatment in ADCLT 2005 consisted of
      80mg atorvastatin compared to placebo for 52 weeks, serum low density lipoprotein
      (LDL) cholesterol was reduced by 54% in the atorvastatin group. Treatment in
      Simons 2002 consisted of 40mg simvastatin compared to placebo for 26 weeks, serum
      LDL cholesterol was reduced by 52% in the simvastatin group. Treatment in LEADe
      2010 consisted of 80mg atorvastatin compared to placebo for 72 weeks, LDL
      cholesterol was reduced by 50.2% by month 3 and remained constant through month
      18. Change in Alzheimer's Disease Assessment Scale- cognitive subscale (ADAS-Cog)
      from baseline was a primary outcome in 3 studies; when data were pooled there was
      considerable heterogeneity so the random effects model was used, statins did not
      provide any beneficial effect in this cognitive measure [mean difference -1.12,
      95% CI -3.99, 1.75, p = 0.44]. All studies provided change in Mini Mental State
      Examination (MMSE) from baseline; again random effects model was used due to
      considerable heterogeneity: there was no significant benefit from statins in this
      cognitive measure when the data were pooled [mean difference -1.53, 95% CI -3.28,
      0.21, p = 0.08]. There was some evidence that patients on statins in ADCLT 2005
      maintained better cognitive function if serum cholesterol was high at baseline,
      MMSE was higher at baseline or if they had an apolipoprotein E4 allele present.
      This would need to be confirmed in larger studies however. Treatment related
      adverse effects were available from two studies, LEADe 2010 and Simons 2002; when
      data were pooled there was no significant difference between statins and placebo
      [odds ratio 2.45, 95% CI 0.69, 8.62, p = 0.16]. There was no significant
      difference in global function, behaviour or activities of daily living in the
      statin and placebo groups. One large randomised controlled trial (RCT) ( CLASP
      2008) has not yet published its results. There were no studies identified
      assessing role of statins in treatment of VaD. There was no evidence that statins
      were detrimental to cognition. AUTHORS' CONCLUSIONS: There is insufficient
      evidence to recommend statins for the treatment of dementia. Analysis from the
      studies available, including one large RCT, indicate statins have no benefit on
      the outcome measures ADAS-Cog or MMSE. We need to await full results from CLASP
      2008 before we can be certain. This Cochrane review will be updated as these
      results become available.

PMID- 20687090
TI  - Gene therapy for sickle cell disease.
AB  - BACKGROUND: Sickle cell disease encompasses a group of genetic disorders
      characterized by the presence of at least one hemoglobin S (Hb S) allele, and a
      second abnormal allele that could allow abnormal hemoglobin polymerisation
      leading to a symptomatic disorder.Autosomal recessive disorders (such as sickle
      cell disease) are good candidates for gene therapy because a normal phenotype can
      be restored in diseased cells with only a single normal copy of the mutant gene.
      OBJECTIVES: The objectives of this review are:- to determine whether gene therapy
      can improve survival and prevent symptoms and complications associated with
      sickle cell disease;- to examine the risks of gene therapy against the potential
      long-term gain for people with sickle cell disease. SEARCH STRATEGY: We searched
      the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies
      Trials Register, which comprises of references identified from comprehensive
      electronic database searches and searching relevant journals and abstract books
      of conference proceedings.Date of the most recent search of the Group's
      Haemoglobinopathies Trials Register: 05 March 2010. SELECTION CRITERIA: All
      randomised or quasi-randomised clinical trials (including any relevant phase 1, 2
      or 3 trials) of gene therapy for all individuals with sickle cell disease,
      regardless of age or setting. DATA COLLECTION AND ANALYSIS: No trials of gene
      therapy for sickle cell disease were found. MAIN RESULTS: No trials of gene
      therapy for sickle cell disease were reported. AUTHORS' CONCLUSIONS: No
      randomised or quasi-randomised clinical trials of gene therapy for sickle cell
      disease were reported. Thus, no objective conclusions or recommendations in
      practice can be made on gene therapy for sickle cell disease. This systematic
      review has identified the need for well-designed, randomised controlled trials to
      assess the benefits and risks of gene therapy for sickle cell disease.

PMID- 20687091
TI  - Pharmacological interventions for antisocial personality disorder.
AB  - BACKGROUND: Antisocial personality disorder (AsPD) is associated with a wide
      range of disturbance including persistent rule-breaking, criminality, substance
      misuse, unemployment, homelessness and relationship difficulties. OBJECTIVES: To
      evaluate the potential beneficial and adverse effects of pharmacological
      interventions for people with AsPD. SEARCH STRATEGY: We searched the Cochrane
      Central Register of Controlled Trials (The Cochrane Library 2009, Issue 3),
      MEDLINE (1950 to September 2009), EMBASE (1980 to 2009, week 37), CINAHL (1982 to
      September 2009), PsycINFO (1872 to September 2009) , ASSIA (1987 to September
      2009) , BIOSIS (1985 to September 2009), COPAC (September 2009), National
      Criminal Justice Reference Service Abstracts (1970 to July 2008), Sociological
      Abstracts (1963 to September 2009), ISI-Proceedings (1981 to September 2009),
      Science Citation Index (1981 to September 2009), Social Science Citation Index
      (1981 to September 2009), SIGLE (1980 to April 2006), Dissertation Abstracts
      (September 2009), ZETOC (September 2009) and the metaRegister of Controlled
      Trials (September 2009). SELECTION CRITERIA: Controlled trials in which
      participants with AsPD were randomly allocated to a pharmacological intervention
      and a placebo control condition. Two trials comparing one drug against another
      without a placebo control are reported separately. DATA COLLECTION AND ANALYSIS:
      Three review authors independently selected studies. Two review authors
      independently extracted data. We calculated mean differences, with odds ratios
      for dichotomous data. MAIN RESULTS: Eight studies met the inclusion criteria
      involving 394 participants with AsPD. Data were available from four studies
      involving 274 participants with AsPD. No study set out to recruit participants
      solely on the basis of having AsPD, and in only one study was the sample entirely
      of AsPD participants. Eight different drugs were examined in eight studies. Study
      quality was relatively poor. Inadequate reporting meant the data available were
      generally insufficient to allow any independent statistical analysis. The
      findings are limited to descriptive summaries based on analyses carried out and
      reported by the trial investigators. All the available data were derived from
      unreplicated single reports. Only three drugs (nortriptyline, bromocriptine,
      phenytoin) were effective compared to placebo in terms of improvement in at least
      one outcome. Nortriptyline was reported in one study as superior for men with
      alcohol dependency on mean number of drinking days and on alcohol dependence, but
      not for severity of alcohol misuse or on the patient's or clinician's rating of
      drinking. In the same study, both nortriptyline and bromocriptine were reported
      as superior to placebo on anxiety on one scale but not on another. In one study,
      phenytoin was reported as superior to placebo on the frequency and intensity of
      aggressive acts in male prisoners with impulsive (but not premeditated)
      aggression. In the remaining two studies, both amantadine and desipramine were
      not superior to placebo for adults with opioid and cocaine dependence, and
      desipramine was not superior to placebo for men with cocaine dependence. AUTHORS'
      CONCLUSIONS: The body of evidence summarised in this review is insufficient to
      allow any conclusion to be drawn about the use of pharmacological interventions
      in the treatment of antisocial personality disorder.

PMID- 20687093
TI  - Aerosolized prostacyclin for acute lung injury (ALI) and acute respiratory
      distress syndrome (ARDS).
AB  - BACKGROUND: Acute lung injury (ALI) and acute respiratory distress syndrome
      (ARDS) are critical conditions that are associated with high mortality and
      morbidity. Aerosolized prostacyclin has been used to improve oxygenation despite
      the limited evidence available so far. OBJECTIVES: To systematically assess the
      benefits and harms of aerosolized prostacyclin in critically ill patients with
      ALI and ARDS. SEARCH STRATEGY: We identified randomized clinical trials (RCTs)
      from electronic databases: the Cochrane Central Register of Controlled Trials
      (CENTRAL) (The Cochrane Library 2010, Issue 1); MEDLINE; EMBASE; Science Citation
      Index Expanded; International Web of Science; CINAHL; LILACS; and the Chinese
      Biomedical Literature Database (to 31st January 2010). We contacted trial authors
      and manufacturers in the field. SELECTION CRITERIA: We included all RCTs,
      irrespective of blinding or language, that compared aerosolized prostacyclin with
      no intervention or placebo in either children or adults with ALI or ARDS. DATA
      COLLECTION AND ANALYSIS: Two authors independently abstracted data and resolved
      any disagreements by discussion. We presented pooled estimates of the
      intervention effects as relative risks (RR) with 95% confidence intervals (CI)
      for dichotomous outcomes. Our primary outcome measure was all cause mortality. We
      planned to perform subgroup and sensitivity analyses to assess the effect of
      aerosolized prostacyclin in adults and children, and on various clinical and
      physiological outcomes. We assessed the risk of bias through assessment of
      methodological trial components and the risk of random error through trial
      sequential analysis. MAIN RESULTS: We included one paediatric RCT with low risk
      of bias and involving a total of 14 critically ill children with ALI or ARDS.
      Aersosolized prostacyclin over less than 24 hours did not reduce overall
      mortality at 28 days (RR 1.50, 95% CI 0.17 to 12.94) compared with aerosolized
      saline (a total of three deaths). The authors did not encounter any adverse
      events such as bleeding or organ dysfunction. We were unable to perform the
      prespecified subgroups and sensitivity analyses or trial sequential analysis due
      to the limited number of RCTs. We were also not able to assess the safety and
      efficacy of aerosolized prostacyclin for ALI and ARDS. We found two ongoing
      trials, one involving adults and the other paediatric participants. The adult
      trial has been finalized but the data are not yet available. AUTHORS'
      CONCLUSIONS: There is no current evidence to support or refute the routine use of
      aerosolized prostacyclin for patients with ALI and ARDS. There is an urgent need
      for more randomized clinical trials.

PMID- 20687092
TI  - Different methods for the induction of labour in outpatient settings.
AB  - BACKGROUND: Induction of labour is carried out for a variety of indications and
      using a range of pharmacological, mechanical and other methods. For women at low
      risk, some methods of induction of labour may be suitable for use in outpatient
      settings. OBJECTIVES: To examine pharmacological and mechanical interventions to
      induce labour in outpatient settings in terms of feasibility, effectiveness,
      maternal satisfaction, healthcare costs and, where information is available,
      safety. The review complements existing reviews on labour induction examining
      effectiveness and safety. SEARCH STRATEGY: We searched the Cochrane Pregnancy and
      Childbirth Group's Trials Register (December 2009) and reference lists of
      retrieved studies. SELECTION CRITERIA: We included randomised controlled trials
      examining outpatient cervical ripening or induction of labour with
      pharmacological agents or mechanical methods. DATA COLLECTION AND ANALYSIS: Two
      authors independently extracted data and assessed eligible papers for risk of
      bias. We checked all data after entry into review manager software. MAIN RESULTS:
      We included 28 studies with 2616 women examining different methods of induction
      of labour where women received treatment at home or were sent home after initial
      treatment and monitoring in hospital.Studies examined vaginal and intracervical
      PGE(2), vaginal and oral misoprostol, isosorbide mononitrate, mifepristone,
      oestrogens, and acupuncture. Overall, the results demonstrate that outpatient
      induction of labour is feasible and that important adverse events are rare. There
      was no strong evidence that agents used to induce labour in outpatient settings
      had an impact (positive or negative) on maternal or neonatal health. There was
      some evidence that, compared to placebo or no treatment, induction agents reduced
      the need for further interventions to induce labour, and shortened the interval
      from intervention to birth. We were unable to pool results on outcomes relating
      to progress in labour as studies tended to measure a very broad range of
      outcomes.There was no evidence that induction agents increased interventions in
      labour such as operative deliveries. Only two studies provided information on
      women's views about the induction process, and overall there was very little
      information on the costs to health service providers of different methods of
      labour induction in outpatient settings. AUTHORS' CONCLUSIONS: Induction of
      labour in outpatient settings appears feasible. We do not have sufficient
      evidence to know which induction methods are preferred by women, or the
      interventions that are most effective and safe to use in outpatient settings.

PMID- 20687094
TI  - Interventions for treating osteochondral defects of the talus in adults.
AB  - BACKGROUND: Osteochondral defects of the talus are usually a consequence of
      trauma. They can cause chronic pain and serious disability. Various
      interventions, non-surgical and surgical, have been used for treating these
      defects. OBJECTIVES: The objective of this review is to determine the benefits
      and harms of the interventions used for treating osteochondral defects of the
      talus in adults. SEARCH STRATEGY: We searched the Cochrane Bone, Joint and Muscle
      Trauma Group Specialised Register, the Cochrane Central Register of Controlled
      Trials, MEDLINE, MEDLINE In-Process, EMBASE, Current Controlled Trials, the WHO
      International Clinical Trials Registry Platform and reference lists of articles.
      Date of last search: December 2009. SELECTION CRITERIA: Eligible for inclusion
      were any randomised or quasi-randomised controlled clinical trials evaluating
      interventions for treating osteochondral defects of the talus in adults. Our
      primary outcomes included pain, ankle function, treatment failure (unresolved
      symptoms or reoperation) and health-related quality of life. Preference was given
      to validated, patient-reported outcome measures. DATA COLLECTION AND ANALYSIS:
      Two review authors independently evaluated trials for inclusion and, for the
      included trial, independently assessed the risk of bias and extracted data. MAIN
      RESULTS: One small trial with 15 participants and six months follow-up was
      included. This trial was published only as a conference abstract, which provided
      inadequate information to judge the trial's methods and no numerical results. The
      trial reported that a series of three intra-articular hyaluronan injections
      started three weeks after arthroscopic microfracture did not to improve pain but
      may have improved one aspect of mobility. There were no available data to check
      this claim. AUTHORS' CONCLUSIONS: There is insufficient evidence from randomised
      trials to determine which interventions are best for osteochondral defects of the
      talus in adults. High quality randomised trials are required to guide non
      surgical and surgical treatment decisions for these injuries.

PMID- 20687095
TI  - Spironolactone for hypertension.
AB  - BACKGROUND: Spironolactone is an aldosterone antagonist, considered fourth line
      therapy for hypertension in patients already treated with multiple medications.
      OBJECTIVES: Primary: to determine the effect of spironolactone on patient
      mortality, morbidity, and to quantify the magnitude of blood pressure lowering
      effect of spironolactone monotherapy.Secondary: to determine the prevalence of
      adverse reactions observed with spironolactone monotherapy and to determine if
      there is a blood-pressure lowering dose response with spironolactone. SEARCH
      STRATEGY: We searched the following databases: Cochrane Central Register of
      Controlled Trials (3rd Quarter 2009), MEDLINE (2005 - Sept. 2009), and EMBASE
      (2007 - Sept. 2009). References from retrieved studies were reviewed to identify
      any studies missed in the initial search. No language restrictions were applied.
      SELECTION CRITERIA: We selected RCTs studying patients with primary hypertension.
      We excluded studies of patients with secondary or gestational hypertension, and
      studies where patients were receiving multiple antihypertensives. DATA COLLECTION
      AND ANALYSIS: Two reviewers independently reviewed the search results for studies
      meeting our criteria. Three reviewers extracted data and assessed trial quality
      using a standardized data extraction form. Data synthesis and analysis was
      performed using RevMan 5. MAIN RESULTS: Meta-analysis of the 5 cross-over studies
      found a reduction in SBP of 20.09 mmHg (95%CI:16.58-23.06,p<0.00001) and a 6.75
      mmHg (95%CI:4.8-8.69,p<0.00001) reduction in DBP. These results were
      statistically significant and there was no evidence of heterogeneity between the
      studies. There may be a dose response effect with spironolactone up to 50 mg/day,
      but the confidence intervals around the mean end-of-study blood pressure for
      doses ranging 25-500 mg/day all overlapped. In other words, it appears that doses
      >50mg/day do not produce further reductions in either SBP or DBP. One cross-over
      study found that spironolactone 25 mg/day did not statistically significantly
      change SBP or DBP compared to placebo, SBP: -9.9 (95%CI:-21.15,1.35); DBP -2.34
      (95%CI:-7.92,3.06). AUTHORS' CONCLUSIONS: From the limited available evidence,
      spironolactone appears to lower blood pressure compared to placebo to a similar
      degree in patients with primary (essential) hypertension when doses of 100-500
      mg/day are given. A dose of 25 mg/day did not statistically significantly reduce
      systolic or diastolic blood pressure, compared to placebo. Given the lack of a
      dose-response, coupled with a possible increased risk in adverse events with
      higher doses, doses of 25 to 100 mg/day are reasonable. There is no evidence of
      the effect of spironolactone on clinical outcomes in hypertensive patients.

PMID- 20687096
TI  - Outreach strategies for expanding health insurance coverage in children.
AB  - BACKGROUND: Health insurance has the potential to improve access to health care
      and protect people from healthcare costs when they are ill. However, coverage is
      often low, particularly in people most in need of protection. OBJECTIVES: To
      assess the effectiveness of outreach strategies for expanding insurance coverage
      of children who are eligible for health insurance schemes. SEARCH STRATEGY: We
      searched the Cochrane Effective Practice and Organisation of Care Group (EPOC)
      Specialised Register (The Cochrane Library 2009, Issue 2), PubMed (January 1951
      to January 2010), EMBASE (January 1966 to April 2009), PsycINFO (January 1967 to
      April 2009) and other relevant databases and websites. In addition, we searched
      the reference lists of included studies and relevant reviews, and carried out a
      citation search for included studies to find more potentially relevant studies.
      SELECTION CRITERIA: Randomised controlled trials, controlled clinical trials,
      controlled before-after studies and interrupted time series which evaluated the
      effects of outreach strategies on increasing health insurance coverage for
      children. We defined outreach strategies as measures to improve the
      implementation of existing health insurance to enrol more eligible populations.
      This included increasing awareness of schemes, modifying enrolment, improving
      management and organis ation of insurance schemes, and mixed strategies. DATA
      COLLECTION AND ANALYSIS: Two review authors independently extracted data and
      assessed the risk of bias . We narratively summari sed the data. MAIN RESULTS: We
      included two studies, both from the United States. One randomised controlled
      trial study with a low risk of bias showed that community- based case managers
      who provided health insurance information, application support, and negotiated
      with the insurer were effective in enrolling and maintaining enrolment of Latino
      American children into health insurance schemes (n = 257). The second quasi
      randomised controlled trial, with an unclear risk of bias (n = 223), indicated
      that handing out insurance application materials in hospital emergenc y
      departments can increase enrolment of children into health insurance. AUTHORS'
      CONCLUSIONS: The two studies included in this review provide evidence that in the
      US providing health insurance information and application assistance, and handing
      out application materials in hospital emergency departments can probably both
      improve insurance coverage of children. Further studies evaluating the
      effectiveness of different outreach strategies for expanding health insurance
      coverage of children in different countries are needed, with careful attention
      given to study design.

PMID- 20687097
TI  - Stavudine or zidovudine in three-drug combination therapy for initial treatment
      of HIV infection in antiretroviral-naive individuals.
AB  - BACKGROUND: The introduction of highly active antiretroviral therapy (ART) as
      treatment for HIV infection has greatly improved mortality and morbidity for
      adults and children living with HIV around the world. Two common medications
      given in first-line antiretroviral therapy are the nucleoside reverse
      transcriptase inhibitors (NRTI) stavudine (d4T) or zidovudine (AZT). OBJECTIVES:
      To assess the efficacy of d4T compared to AZT in combination with one NRTI and
      one non-nucleoside reverse transcriptase inhibitor (NNRTI), two additional
      NNRTIs, or one NRTI and one protease inhibitor (PI), as part of first-line ART
      for HIV-infected people in low-resource settings. SEARCH STRATEGY: Standard
      Cochrane methods were used to search electronic databases and conference
      proceedings with relevant search terms without limits to language. SELECTION
      CRITERIA: Randomised controlled trials of HIV-infected patients 5 years of age
      and older were included. Primary outcomes of interest included mortality, severe
      adverse events, virologic response to ART, and adherence/tolerance/retention.
      Secondary outcomes included immunologic response to ART, development of ART drug
      resistance, and prevention of sexual transmission of HIV. DATA COLLECTION AND
      ANALYSIS: Two authors assessed each reference for inclusion and exclusion
      criteria established a priori. Data were abstracted independently using a
      standardised abstraction form. MAIN RESULTS: Nine randomised controlled trials
      were identified as meeting the inclusion criteria. The nine trials enrolled 2,159
      participants but looked at a multiplicity of drug combinations. Despite this, a
      reasonably robust literature suggests no statistically significant difference
      between the two drug combinations, including severe adverse events and
      adherence/tolerance/retention. The quality of the literature was found overall to
      be low to very low for all key outcomes. Only one study reported on drug
      resistance, and no studies reported on sexual transmission of HIV. The length of
      follow-up time and study settings varied greatly. AUTHORS' CONCLUSIONS: While
      ideally future research would focus on direct comparison of standard therapeutic
      combinations of d4T+3TC+an NNRTI and AZT+3TC+an NNRTI to compare these regimens
      more directly, it is unlikely that additional trials will be mounted.
      Observational studies should focus on understanding outcomes, including toxicity
      and tolerability, in low- and middle-income countries.

PMID- 20687098
TI  - Pharmaceutical policies: effects of restrictions on reimbursement.
AB  - BACKGROUND: Public policy makers and benefit plan managers need to restrain
      rising pharmaceutical drug costs while preserving access and optimizing health
      benefits. OBJECTIVES: To determine the effects of a pharmaceutical policy
      restricting the reimbursement of selected medications on drug use, health care
      utilization, health outcomes and costs (expenditures). SEARCH STRATEGY: We
      searched the 14 major bibliographic databases and websites (to January 2009).
      SELECTION CRITERIA: Included were studies of pharmaceutical policies that
      restrict coverage and reimbursement of selected drugs or drug classes, often
      using additional patient specific information related to health status or need.
      We included randomised controlled trials, non-randomised controlled trials,
      interrupted time series (ITS) analyses, repeated measures studies and controlled
      before-after studies set in large care systems or jurisdictions. DATA COLLECTION
      AND ANALYSIS: Two authors independently extracted data and assessed study
      limitations. Quantitative re-analysis of time series data was undertaken for
      studies with sufficient data. MAIN RESULTS: We included 29 ITS analyses (12 were
      controlled) investigating policies targeting 11 drug classes for restriction.
      Participants were most often senior citizens or low income adult populations, or
      both, in publically subsidized or administered pharmaceutical benefit plans.
      Impact of policies varied by drug class and whether restrictions were implemented
      or relaxed. When policies targeted gastric-acid suppressant and non-steroidal
      anti-inflammatory drug classes, decreased drug use and substantial savings on
      drugs occurred immediately and for up to two years afterwards, with no increase
      in the use of other health services (6 studies). Targeting second generation
      antipsychotic drugs increased treatment discontinuity and the use of other health
      services without reducing overall drug expenditures (2 studies). Relaxing
      restrictions for reimbursement of antihypertensives and statins increased
      appropriate use and decreased overall drug expenditures. Two studies which
      measured health outcomes directly were inconclusive. AUTHORS' CONCLUSIONS:
      Implementing restrictions to coverage and reimbursement of selected medications
      can decrease third-party drug spending without increasing the use of other health
      services (6 studies). Relaxing reimbursement rules for drugs used for secondary
      prevention can also remove barriers to access. Policy design, however, needs to
      be based on research quantifying the harm and benefit profiles of target and
      alternative drugs to avoid unwanted health system and health effects. Health
      impact evaluation should be conducted where drugs are not interchangeable.
      Impacts on health equity, relating to the fair and just distribution of health
      benefits in society (sustainable access to publically financed drug benefits for
      seniors and low income populations, for example), also require explicit
      measurement.

PMID- 20687099
TI  - A rapid and simple RP-HPLC method for quantification of kirenol in rat plasma
      after oral administration and its application to pharmacokinetic study.
AB  - A rapid and simple reverse-phase high-performance liquid chromatography (RP-HPLC)
      was developed and validated for the quantification of kirenol in rat plasma after
      oral administration. Kirenol and darutoside (internal standard, IS) were
      extracted from rat plasma using CleanertTM C(18) solid-phase extraction (SPE)
      cartridge. Analysis of the extraction was performed on a Thermo ODS-2 Hypersil
      C(18) reversed-phase column with a gradient eluent composed of acetonitrile and
      0.1% phosphoric acid. The flow rate was 1.0 mL/min and the detection wavelength
      was set at 215 nm. The calibration curve was linear over the range of 9.756
      133.333 ug/mL (r(2) = 0.9991) in rat plasma. The lower limits of detection and
      quantification were 2.857 and 9.756 ug/mL, respectively. The intra- and inter-day
      precisions (relative standard deviation, RSD) were between 2.24 and 4.46%, with
      accuracies ranging from 91.80 to 102.74%. The extraction recovery ranged from
      98.16 to 107.62% with RSD less than 4.81%. Stability studies showed that kirenol
      was stable in preparation and analytical process. The present method was
      successfully applied to the pharmacokinetic study of kirenol in male Sprague
      Dawley rats after oral administration at a dose of 50 mg/kg.

PMID- 20687100
TI  - On the relative safety of intravenous iron formulations: new answers, new
      questions.

PMID- 20687101
TI  - Acute leukemia presenting with extramedullary diseases and completely normal
      hemogram: an extremely unusual manifestation unique to pre-B ALL.
AB  - Acute lymphoblastic leukemia (ALL) is a clonal hematological disease
      characterized by inadequate normal hematopoiesis secondary to excessive
      proliferation of leukemic blasts and their impaired differentiation. As a result,
      patients usually manifest symptoms related to bone marrow failure. It's very
      uncommon for ALL patients to present with normal hemogram. Herein, we describe
      two patients who presented with excruciating bone pain at orthopedic clinics.
      Osteopathy involving multiple bones was noted initially, but acute leukemia was
      never considered as one of the differential diagnoses because of the completely
      normal hemogram in both cases. Consequently, the diagnosis of leukemia was
      slightly delayed. Upon literature review, we found that ALL patients with solely
      extramedullary diseases and nearly normal hemogram had exclusively pre-B disease.
      We also propose a putative hypothesis for this interesting finding.

PMID- 20687102
TI  - Alteration of cohesin genes in myeloid diseases.
AB  - New genes involved in leukemogenesis, such as ASXL1 and TET2, have been
      identified recently using genomic analyses of DNA from patient samples. We have
      studied by array-comparative genomic hybridization (aCGH) a series of 167 samples
      including myelodysplastic syndromes, chronic myelomonocytic leukemias, and acute
      myeloid leukemias. We found a deletion of the RAD21 and STAG2 genes, which encode
      two components of the cohesin complex. We propose that these alterations may
      compromise the cohesin complex and its regulation of the transcription of genes.

PMID- 20687103
TI  - Immature Plasmodium falciparum gametocytes in bone marrow.

PMID- 20687104
TI  - Megakaryocyte dysplasia in primary myelofibrosis.

PMID- 20687105
TI  - Differential effects of stress on [11C]raclopride and [11C]MNPA binding to
      striatal D2/D3 dopamine receptors: a PET study in conscious monkeys.
AB  - It has been reported that stress and facilitation of dopamine neuronal system are
      closely related. In the present study, the effects of stress on the binding of
      antagonist-based [11C]raclopride and agonist-based (R)-2-CH3O-N-n-
      propylnorapomorphine ([11C]MNPA) to D2/D3 receptors were evaluated in the
      striatum of conscious monkey brain. The stress state assessed from plasma
      cortisol level was negatively correlated with [11C]raclopride binding as
      expected. It was noteworthy that [11C]MNPA binding exhibited a positive
      correlation with stress state; thus, the animals with higher cortisol levels
      showed higher binding to D2/D3 receptors.

PMID- 20687106
TI  - Differential developmental trajectories for CB1 cannabinoid receptor expression
      in limbic/associative and sensorimotor cortical areas.
AB  - Cannabis use during adolescence is associated with an increased risk for
      schizophrenia and other disorders. The neuronal basis is unclear, but prefrontal
      cortical mechanisms have been implicated. Here, we investigated developmental
      changes in the endocannabinoid system by assessing expression and function of the
      CB1 cannabinoid receptor in prefrontal and other cortical areas in juvenile
      (postnatal day 25, P25), adolescent (P40), and adult (P70) rats. Overall, the
      expression of CB1 receptors in the cortex is highest in juveniles and drops
      thereafter toward adult levels. However, CB1 receptor expression follows distinct
      developmental trajectories in different cortical areas. The most pronounced and
      progressive decrease in CB1 expression was observed in medial prefrontal and
      other limbic/associative regions. In contrast, major changes in sensorimotor
      cortices occurred only after P40. We also assessed electrophysiological measures
      of CB1 receptor function and found that CB1-dependent inhibition of synaptic
      transmission in the prefrontal cortex follows the same developmental trajectory
      as observed for receptor expression. Together, these findings indicate that CB1
      receptor-mediated signaling decreases during development but is differentially
      regulated in limbic/associative vs. sensorimotor systems. Therefore, cannabis use
      during adolescence likely differentially affects limbic/associative and
      sensorimotor cortical circuits.

PMID- 20687107
TI  - Prefrontal cell firing in male rats during approach towards sexually receptive
      female: interactions with cocaine.
AB  - The medial prefrontal cortex (mPFC) plays a role in anticipation of rewards and
      goal orientation, properties that are influenced by cocaine administration.
      Single-unit firing was measured in the mPFC of seven male rats during the
      expression of approach responses toward a sexually receptive female. Nose-poking
      in male rats was used as a measure of approach behavior during the following
      periods: a baseline, first exposure to a female, a second baseline 2 h later and
      a second exposure to female 10 min after cocaine (15 mg kg-1 i.p.). Two types of
      excitatory responses were identified. First, a subset of cells (23%) showed
      increased firing activity during nose-poke behavior upon presentation of the
      female, but not before. Another subset of cells (12%) showed increased firing in
      the presence of the female only after cocaine was administered. The present
      results provide preliminary evidence for neurons in the mPFC that are involved in
      sexually motivated approach behavior and that are modulated by cocaine.

PMID- 20687108
TI  - The synthesis and preclinical evaluation in rhesus monkey of [18F]MK-6577 and
      [11C]CMPyPB glycine transporter 1 positron emission tomography radiotracers.
AB  - Two positron emission tomography radiotracers for the glycine transporter 1
      (GlyT1) are reported here. Each radiotracer is a propylsulfonamide-containing
      benzamide and was labeled with either carbon-11 or fluorine-18. [11C]CMPyPB was
      synthesized by the alkylation of a 3-hydroxypyridine precursor using [11C]MeI,
      and [18F]MK-6577 was synthesized by a nucleophilic aromatic substitution reaction
      using a 2-chloropyridine precursor. Each tracer shows good uptake into rhesus
      monkey brain with the expected distribution of highest uptake in the pons,
      thalamus, and cerebellum and lower uptake in the striatum and gray matter of the
      frontal cortex. In vivo blockade and chase studies of [18F]MK-6577 showed a large
      specific signal and reversible binding. In vitro autoradiographic studies with
      [18F]MK-6577 showed a large specific signal in both rhesus monkey and human brain
      slices and a distribution consistent with the in vivo results and those reported
      in the literature. In vivo metabolism studies in rhesus monkeys demonstrated that
      only more-polar metabolites are formed for each tracer. Of these two tracers,
      [18F]MK-6577 was more extensively characterized and is a promising clinical
      positron emission tomography tracer for imaging GlyT1 and for measuring GlyT1
      occupancy of therapeutic compounds.

PMID- 20687109
TI  - The microtubule cytoskeleton acts as a key downstream effector of
      neurotransmitter signaling.
AB  - Microtubules are well known to play a key role in the trafficking of
      neurotransmitters to the synapse. However, less attention has been paid to their
      role as downstream effectors of neurotransmitter signaling in the target neuron.
      Here, we show that neurotransmitter-based signaling to the microtubule
      cytoskeleton regulates downstream microtubule function through several
      mechanisms. These include tubulin posttranslational modification, binding of
      microtubule-associated proteins, release of microtubule-interacting second
      messenger molecules, and regulation of tubulin expression levels. We review the
      evidence for neurotransmitter regulation of the microtubule cytoskeleton,
      focusing on the neurotransmitters serotonin, melatonin, dopamine, glutamate,
      glycine, and acetylcholine. Some evidence suggests that microtubules may even
      play a more direct role in propagating action potentials through conductance of
      electric current. In turn, there is evidence for the regulation of
      neurotransmission by the microtubule cytoskeleton.

PMID- 20687110
TI  - Prenatal exposure to perfluorooctanesulfonate in rat resulted in long-lasting
      changes of expression of synapsins and synaptophysin.
AB  - Both animal and human studies have demonstrated that exposure to chemical
      pollutants during critical developmental period causes adverse consequences later
      in life. In uterus, perfluorooctanesulfonate (PFOS) exposure has been known to
      cause developmental neurotoxicity, such as increased motor activity, reduced
      habitation and impaired cognitive function. The possible mechanism of the
      impaired cognitive function induced by prenatal PFOS exposure was evaluated in
      this study. Pregnant Sprague Dawley (SD) rats were given 0.1, 0.6, and 2.0 mg kg(
      1) birth weight (bw) d(-1) by gavage from gestation day (GD) 0 to GD20. Control
      received 0.5% Tween-20 vehicle (4 ml kg(-1) bw d(-1)). PFOS concentration in
      hippocampus of offspring was observed on postnatal day (PND) 0 and PND21. The
      ultrastructure of hippocampus and the gene expression of synaptic vesicle
      associated proteins in offspring hippocampus, which were important for the
      neurotransmitter release, were investigated. The transmission electron
      photomicrographs of the offspring hippocampus from PFOS-treated maternal groups
      showed the ultrastructure of synapses was negatively affected. The offspring from
      PFOS-treated maternal groups also differed significantly from controls with
      respect to the expression of synaptic vesicle associated proteins. The mRNA
      levels of synapsin1 (Syn1), synapsin2 (Syn2), and synaptophysin (Syp) were
      decreased in treated groups either on PND0 or on PND21. However, the mRNA level
      of synapsin3 (Syn3) decreased in 0.6- and 2.0-mg kg(-1) group on PND0, and showed
      no significant difference among control group and all treated groups on PND21.
      These results indicate that the impairment of cognitive function induced by PFOS
      may be attributed to the lower mRNA levels of synaptic vesicle associated
      proteins and the change of synaptic ultrastructure in hippocampus.

PMID- 20687112
TI  - Developmental changes of cell adhesion molecule expression in the fetal mouse
      liver.
AB  - Developmental changes of cell adhesion molecule expression, especially in
      nonparenchymal cells, have hardly ever been analyzed in the murine liver. The
      present study was undertaken to immunohistochemically examine the expression of
      NCAM, ICAM, VCAM, and N-cadherin during mouse liver development and in fetal
      liver cell cultures. NCAM was transiently expressed in mesenchymal cells of the
      septum transversum and sinusoidal cells in liver development. In vitro studies
      demonstrated that desmin-positive stellate cells expressed this cell adhesion
      molecule. NCAM expression in periportal biliary epithelial cells and connective
      tissue cells also coincided well with bile duct remodeling processes in the
      perinatal periods. Expression of ICAM and VCAM was transiently restricted to
      hepatoblasts, hepatocytes and hemopoietic cells in fetal stages. N-cadherin was
      expressed not only in hepatoblasts and hepatocytes, but also in nonparenchymal
      cells such as endothelial cells, stellate cells and connective tissue cells,
      however the expression was weak. These results suggest that each cell adhesion
      molecule may play an important role during development in hepatic histogenesis,
      including hepatoblast/hepatocyte-stellate cell interactions, hemopoiesis, and
      bile duct morphogenesis.

PMID- 20687111
TI  - Genetic and pharmacological evidence for schizophrenia-related Disc1 interaction
      with GSK-3.
AB  - Recent studies have identified disrupted-in-schizophrenia-1 (DISC1) as a strong
      genetic risk factor associated with schizophrenia. Previously, we have reported
      that a mutation in the second exon of the DISC1 gene [leucine to proline at amino
      acid position 100, L100P] leads to the development of schizophrenia-related
      behaviors in mice. Glycogen synthase kinase-3 (GSK-3) is a serine/threonine
      protein kinase that interacts with the N-terminal region of DISC1 (aa 1-220) and
      has been implicated as an important downstream component in the etiology of
      schizophrenia. Here, for the first time, we show that pharmacological and genetic
      inactivation of GSK-3 reverse prepulse inhibition and latent inhibition deficits
      as well as normalizing the hyperactivity of Disc1-L100P mutants. In parallel to
      these observations, interaction between DISC1 and GSK-3alpha and beta is reduced
      in Disc1-L100P mutants. Our data provide genetic, biochemical, and behavioral
      evidence for a molecular link between DISC1 and GSK-3 in relation to
      psychopathology and highlights the value of missense mutations in dissecting the
      underlying and complex molecular mechanisms of neurological disorders.

PMID- 20687113
TI  - RP-HPLC-DAD method for the estimation of embelin as marker in Embelia ribes and
      its polyherbal formulations.
AB  - Evidence-based herbal products with assured quality are assuming importance for
      complementary and alternative medicine. Traditional medicines by and large are
      not standardized and validated to meet the new requirements. In the present
      study, marker (embelin)-based standardization of a major medicinal plant, Embelia
      ribes and its polyherbal formulations was attempted. Conditions for the
      quantitative extraction of the marker compound embelin from E. ribes fruits and
      herbal formulations were also optimized. Reversed-phase high-performance liquid
      chromatography, coupled with diode array detection (RP-HPLC-DAD) for the
      quantification of embelin was developed and validated. Satisfactory results were
      obtained with respect to linearity (15-250 ug/mL), LOD (3.97 ug/mL), LOQ (13.2
      ug/mL), recovery (99.4-103.8%) and precision (1.43-2.87%). The applicability of
      the method was demonstrated with selected phytopharmaceuticals. The present
      method was sensitive, accurate, simple and reproducible and therefore can be
      recommended for marker-based standardization, and quality assurance of E. ribes
      herbal formulations.

PMID- 20687115
TI  - Blood cells RNA biomarkers as a first long-term detection strategy for EPO abuse
      in horseracing.
AB  - Recombinant human erythropoietins (rHuEPOs) are glycoproteins drugs, produced by
      the pharmaceutical industry to restore production of red blood cells by
      stimulating human bone marrow for which this pathology has been diagnosed. It is
      suspected that these molecules are diverted as doping agents in horseracing to
      enhance oxygen transport and aerobic power in racehorses. Although indirect
      double-blotting or direct liquid chromatography-mass spectrometry (LC-MS) methods
      have been developed to confirm the presence of rHuEPO in a sample, the short
      detection time (48 h) is still a problem for doping control. In this context,
      gene profiling investigation through Serial Analysis of Gene Expression (SAGE)
      has been conducted on seven thoroughbreds treated with Eprex. This functional
      genomic method has been performed from total blood cells collected from each
      animal to assess the mRNA expression consecutive to rHuEPO injections. Sample
      pooling was chosen as a powerful, cost-effective, and rapid means of identifying
      the most common and specific changes in terms of gene expression profile and to
      eliminate individual variation. Consequently, three SAGE libraries were
      constructed, before, during, and after Eprex treatment. More than 71 440 mRNA
      signatures were observed and subjected to statistical analysis; 49 differentially
      expressed genes were identified and analyzed by qPCR. From the selected gene
      list, were defined as potential biomarkers in terms of their low inter-individual
      variation and capacity as strong markers of rHuEPO administration up to 60 days
      after the beginning of the doping period. In this paper, a new strategy is
      proposed to the horseracing industry to prevent rHuEPO abuse.

PMID- 20687116
TI  - Increased frontoparietal integration after stroke and cognitive recovery.
AB  - The neural mechanism by which patients spontaneously recover cognitive function
      after brain injury is not understood. Here we demonstrate for the first time that
      aphasic patients, who have largely recovered language function, show increased
      frontoparietal integration. A similar change in functional connectivity is also
      observed when normal subjects are exposed to adverse listening conditions. Thus,
      compensation for inefficient language processing is associated with increased
      integration between parts of the language network critical to language control.
      This change reflects greater top-down control of speech comprehension and
      provides a mechanism by which language impairments after stroke may be
      compensated for.

PMID- 20687117
TI  - Lack of shunt response in suspected idiopathic normal pressure hydrocephalus with
      Alzheimer disease pathology.
AB  - To determine the impact of cortical Alzheimer disease pathology on shunt
      responsiveness in individuals treated for idiopathic normal pressure
      hydrocephalus (iNPH), 37 patients clinically diagnosed with iNPH participated in
      a prospective study in which performance on neurologic, psychometric, and gait
      measures before and 4 months after shunting was correlated with amyloid beta
      plaques, neuritic plaques, and neurofibrillary tangles observed in cortical
      biopsies obtained during shunt insertion. No complications resulted from biopsy
      acquisition. Moderate to severe pathology was associated with worse baseline
      cognitive performance and diminished postoperative improvement on NPH symptom
      severity scales, gait measures, and cognitive instruments compared to patients
      lacking pathology.

PMID- 20687118
TI  - Removal of thallium by deferasirox in rats as biological model.
AB  - The present research aimed to characterize the potential efficiency of
      deferasirox in removing thallium after its administration for 30 days following
      two dose levels of 20 and 160 MUm of thallium (III) chloride to male Wistar rats
      every day. After thallium administration some abnormal clinical signs such as red
      staining around the eyes, greenish mottling on the liver, weakness, loss of hair
      and weight, were observed in animals. Deferasirox was given orally to different
      groups of rats for a period of one week immediately after thallium
      administration. After chelation therapy, animals were killed by exsanguination
      from the abdominal aorta, and then thallium and iron concentrations in various
      tissues were determined by standard addition method. The chelation therapy
      results showed that deferasirox was able to remove thallium ions from the body
      and clinical symptoms were also reduced.

PMID- 20687119
TI  - Adrenocortical hypertrophy: establishing cause and toxicological significance.
AB  - The primary cause of adrenocortical hypertrophy is increased adrenocorticotrophic
      hormone (ACTH) stimulation. In toxicology studies, such a condition can arise as
      a result of the stress response, but it may also occur due to deficient
      glucocorticoid feedback regulation of ACTH due to toxicity to the adrenal cortex.
      This latter condition is defined as adrenocortical insufficiency and represents a
      serious adverse toxic effect on the function of the adrenal cortex.
      Adrenocortical hypertrophy may occur in the absence of other adrenocortical
      lesions such that a toxicopathological mechanism is not obvious, for example by
      pharmacological inhibition of steroidogenesis at the biochemical level. This
      review discusses the different aetiological factors and mechanisms producing
      adrenocortical hypertrophy. The need for further evidence in ascribing findings
      to stress is discussed, as is a protocol for establishing differential diagnoses
      between stress-induced and toxicity-induced adrenocortical hypertrophy, which is
      useful in cases where there are no other histopathological lesions in the adrenal
      cortex. It is concluded that all cases of adrenocortical hypertrophy require
      further investigation or evidence to ascribe such findings to either stress or
      adrenocortical inhibition/insufficiency, and that all cases of adrenocortical
      insufficiency (whether due to a histopathological lesion or reversible
      pharmacological enzyme inhibition) represent a serious adverse effect that must
      be properly considered in toxicological risk assessment.

PMID- 20687120
TI  - Feigning in adjudicative competence evaluations.
AB  - Competence to stand trial (adjudicative competence) is the most requested
      forensic psychiatric evaluation, with an estimated 60,000 referrals annually. The
      challenge of detecting feigned incompetence has not been systematically studied
      until the past decade. Estimates of feigned adjudicative incompetence vary from 8
      to 21%. This article reviews techniques for detecting malingered psychosis and
      malingered cognitive impairment during competence evaluations. Specific
      techniques for assessing feigned adjudicative incompetence and estimating the
      malingerer's genuine abilities are discussed. A stepwise approach to suspected
      feigned adjudicative incompetence is proffered.

PMID- 20687121
TI  - Pathological gambling in Parkinson disease is reduced by amantadine.
AB  - To investigate the possible efficacy of amantadine in the control of pathological
      gambling (PG) associated with Parkinson disease (PD), 17 PD patients with PG were
      randomly selected for a double-blind crossover study with amantadine 200mg/day
      versus placebo and an open follow-up. Assessments included PG-specific scales
      (Yale-Brown Obsessive-Compulsive Scale for PG, Gambling-Symptom Assessment Scale,
      South Oaks Gambling Screen) and assessment of expenditures and time spent
      gambling. Amantadine abolished or reduced PG in all treated patients, as
      confirmed by scale score and daily expenditure reduction. Amantadine might be
      useful to treat PG. The effect of amantadine, acting as an antiglutamatergic
      agent, also opens new insights into the pathogenesis of PG.

PMID- 20687123
TI  - A re-evaluation of the influence of maternal insulin-dependent diabetes on fetal
      nuchal translucency thickness and first-trimester maternal serum biochemical
      markers of aneuploidy.
AB  - OBJECTIVE: To evaluate the influence of maternal insulin-dependent diabetes
      mellitus (IDDM) on maternal serum free beta-hCG, pregnancy-associated plasma
      protein-A (PAPP-A) and fetal nuchal translucency (NT) thickness from 11 weeks to
      13 weeks 6 days of gestation in a large cohort of women screened prospectively
      for chromosomal anomalies. METHODS: Information on maternal IDDM status, maternal
      serum biochemical marker levels and fetal NT were collected from the prenatal
      screening computer records. On total, the control group included 83,972 and the
      IDDM group included 489 pregnancies. The median-corrected free beta-hCG and PAPP
      A, expressed as MoM, and fetal NT, expressed as delta values, in the IDDM and non
      IDDM groups were compared. RESULTS: There were no significant differences between
      the IDDM and non-IDDM groups in median-corrected free beta-hCG (IDDM 1.01 MoM,
      non-IDDM 1.01 MoM; p = 0.970), or mean delta NT (IDDM 0.00 mm, non-IDDM 0.02 mm;
      p = 0.412). However, the median-corrected PAPP-A was significantly lower (IDDM
      0.88 MoM, non-IDDM 1.03 MoM; p < 0.0001). CONCLUSIONS: In pregnancies with
      maternal IDDM, first-trimester screening for chromosomal defects does not require
      adjustments for the measured fetal NT and maternal serum free beta-hCG. However,
      for PAPP-A the 15% reduction is large enough to require correction in the
      calculation of risks for chromosomal defects.

PMID- 20687122
TI  - In vitro cardiomyogenic potential of human amniotic fluid stem cells.
AB  - Stem cell therapy for damaged cardiac tissue is currently limited by a number of
      factors, including inability to obtain sufficient cell numbers, the potential
      tumorigenicity of certain types of stem cells and the possible link between stem
      cell therapy and the development of malignant arrhythmias. In this study, we
      investigated whether human amniotic fluid-derived stem (hAFS) cells could be a
      potential source of cells for cardiac cell therapy, by testing the in vitro
      differentiation capabilities. Undifferentiated hAFS cells express several cardiac
      genes, including the transcription factor mef2, the gap junction connexin43, and
      H- and N-cadherin. A 24 h incubation with 5-aza-2'-deoxycytidine (5-AZA-dC)
      induced hAFS cell differentiation along the cardiac lineage. Evidence for this
      differentiation included morphological changes, upregulation of cardiac-specific
      genes (cardiac troponin I and cardiac troponin T) and redistribution of
      connexin43, as well as downregulation of the stem cell marker SRY-box 2 (sox2).
      When co-cultured with neonatal rat cardiomyocytes (NRCs), hAFS cells formed both
      mechanical and electrical connections with the NRCs. Dye transfer experiments
      showed that calcein dye could be transferred from NRCs to hAFS cells through
      cellular connections. The gap junction connexin43 likely involved in the
      communication between the two cell types, because 12-O-tetradecanoylphorbol 13
      acetate (TPA) could partially block cellular crosstalk. We conclude that hAFS
      cells can be differentiated into a cardiomyocyte-like phenotype and can establish
      functional communication with NRCs. Thus, hAFS cells may potentially be used for
      cardiac cell therapy.

PMID- 20687124
TI  - Progenitor-derived endothelial cell response, platelet reactivity and
      haemocompatibility parameters indicate the potential of NaOH-treated
      polycaprolactone for vascular tissue engineering.
AB  - The haemocompatibility of NaOH-treated poly(epsilon-caprolactone) (PCL) has been
      evaluated in vitro by analysing several parameters, including plasma
      recalcification time, whole blood clotting time and platelet adhesion/activation.
      NaOH-treated PCL films showed a significant decrease in the clot formation speed
      and a reduced number of adhered platelets, which mainly exhibited non-activated
      morphologies. Furthermore, mature endothelial cells derived from peripheral
      endothelial progenitor cells were cultured on the polymer to investigate the
      effects of the endothelial lining on polymer haemocompatibility. Interestingly,
      cells cultured on NaOH-treated PCL films showed a significant stimulation of NO
      production. Although further research is required, NaOH treatment could be an
      interesting and simple strategy to modify PCL-based materials in order to enhance
      endothelial NO production, where compromised, and provide a better interaction of
      the scaffold with the blood components. In conclusion, these results reinforce
      the use of NaOH-treated PCL as a haemocompatible polymer for vascular tissue
      engineering applications.

PMID- 20687125
TI  - A new approach to heart valve tissue engineering: mimicking the heart ventricle
      with a ventricular assist device in a novel bioreactor.
AB  - The 'biomimetic' approach to tissue engineering usually involves the use of a
      bioreactor mimicking physiological parameters whilst supplying nutrients to the
      developing tissue. Here we present a new heart valve bioreactor, having as its
      centrepiece a ventricular assist device (VAD), which exposes the cell-scaffold
      constructs to a wider array of mechanical forces. The pump of the VAD has two
      chambers: a blood and a pneumatic chamber, separated by an elastic membrane.
      Pulsatile air-pressure is generated by a piston-type actuator and delivered to
      the pneumatic chamber, ejecting the fluid in the blood chamber. Subsequently,
      applied vacuum to the pneumatic chamber causes the blood chamber to fill. A
      mechanical heart valve was placed in the VAD's inflow position. The tissue
      engineered (TE) valve was placed in the outflow position. The VAD was coupled in
      series with a Windkessel compliance chamber, variable throttle and reservoir,
      connected by silicone tubings. The reservoir sat on an elevated platform,
      allowing adjustment of ventricular preload between 0 and 11 mmHg. To allow for
      sterile gaseous exchange between the circuit interior and exterior, a 0.2 um
      filter was placed at the reservoir. Pressure and flow were registered downstream
      of the TE valve. The circuit was filled with culture medium and fitted in a
      standard 5% CO(2) incubator set at 37  degrees C. Pressure and flow waveforms
      were similar to those obtained under physiological conditions for the pulmonary
      circulation. The 'cardiomimetic' approach presented here represents a new
      perspective to conventional biomimetic approaches in TE, with potential
      advantages.

PMID- 20687126
TI  - Traditional coating techniques in scanning electron microscopy compared to
      uncoated charge compensator technology: looking at human blood fibrin networks
      with the ZEISS ULTRA Plus FEG-SEM.
AB  - Scanning electron microscopy (SEM) studies surface morphology. Biological
      material needs to be coated to render the material conductive, and gold coating
      is traditionally used, although other coating material like carbon and ruthenium
      vapors may also be used. With modern SEM technology (e.g., ZEISS ULTRA Plus FEG
      SEM), we are able to work at very low kilovolts and also view fine surface
      structure in much better detail than with previous older technology. Some
      machines also allow for the study of uncoated material, although this is usually
      not done with biological material. This study focuses on surface clarity by
      comparing gold, ruthenium vapor, and carbon coating techniques for biological
      material. Human fibrin networks are used as example. Uncoated specimens are also
      viewed with a ZEISS ULTRA Plus FEG-SEM because of its unique nitrogen charge
      compensator, and here, the first micrographs for uncoated human fibrin networks
      versus carbon, gold, and ruthenium coating are shown. We conclude that gold
      coating for biological material is not preferable with the latest SEM machines,
      as this method forms gold islands on top of the biological material and therefore
      produces a false surface morphology.

PMID- 20687127
TI  - Ultrastructural localization of fructose-1,6-bisphosphatase in mouse brain.
AB  - Fructose-1,6-bisphosphatase has been studied in adult mouse brain of different
      ages using an antibody directed against the liver isoform. The presence of liver
      fructose-1,6-bisphosphatase in cerebellum, cerebral cortex, and hippocampus was
      assayed using Western blot and different immunocytochemical techniques.
      Immunocytochemistry with peroxidase reaction product was used to locate fructose
      1,6-bisphosphatase in both neurons and astrocytes in the same areas, as well as
      in the rest of the brain, at light and electron microscope levels. Double
      immunofluorescence with neuronal or astrocytic markers confirmed the neuronal and
      astrocytic location of fructose-1,6-bisphosphatase in confocal microscope images.
      At the subcellular level, fructose-1,6-bisphosphatase was located in the nuclear
      and cytoplasmic compartments of both neurons and astrocytes, at all ages studied.
      Ultrastructurally, immunostaining appeared as small patches in the nucleus and
      the cytosol. In addition, immunostaining was present over the outer mitochondrial
      membrane, the plasma membrane, and the membranes of the rough endoplasmic
      reticulum and nuclear envelope, but not over Golgi membranes. In the neuropil
      fructose-1,6-bisphosphatase was located in dendritic spines, as well as in
      abundant astrocytic processes that, in some cases, surrounded immunopositive
      synapses. The possible role of fructose-1,6-bisphosphatase in neurons and
      astrocytes is discussed.

PMID- 20687128
TI  - Authentication of Chinese Materia Medica decoction dregs, part 1: comparison of
      morphological and microscopic features of four Chinese Materia Medica before and
      after decoction.
AB  - Chinese Materia Medica (CMM) decoction dregs are the residues of medicinal
      materials after decoction. Accurate identification of CMM in decoction dregs will
      be helpful for exploring the causes of poisoning or other medical incidents
      arising after the ingestion of CMM decoctions. To determine how decoction affects
      the characteristics used to authenticate specific CMM, a systematic study was
      carried out. In this study, two pairs of Materia Medica that are commonly
      confused-namely, Baizhu (Atractylodis Macrocephalae Rhizoma) and Cangzhu
      (Atractylodis Rhizoma), Baishao (Paeoniae Alba Radix) and Chishao (Paeoniae Rubra
      Radix)-were chosen for investigation. Each pair of Materia Medica has similar
      morphology in appearance, but they have different functions in Chinese clinic.
      After decoction, with regard to gross morphological characters, the results
      showed that bark and wood could be easily distinguished. The striation of vessels
      and fibers became more prominent because of the contraction of parenchymatous
      cells, but the lignified cells did not. As for the microscopic characteristics,
      the cells with thickened walls, such as stone cells and fibers, were basically
      stable. Most of the parenchymatous cells were broken. Crystals of calcium oxalate
      showed no changes as they were insoluble in water. Starch granules were
      gelatinized and aggregated in parenchymatous cells. Inulins were substantially
      reduced in number as they dissolved in water during decoction. According to these
      changes in morphological and microscopic characteristics after decoction, the
      dregs of two pairs of Materia Medica could be distinguished.

PMID- 20687129
TI  - 1, 2 di-substituted idopyranose from Vitex negundo L. protects against
      streptozotocin-induced diabetes by inhibiting nuclear factor-kappa B and
      inducible nitric oxide synthase expression.
AB  - The aim of this study is to investigate the mechanism of an action of compound
      isolated from Vitex negundo in streptozotocin-induced diabetic mice. Light
      microscopic examination of liver, kidney and pancreatic sections of
      streptozotocin-induced diabetic mice showed changes like coarsening of acinar
      cells of endoplasmic reticulum, destruction of beta-cells, and alteration in
      their secretory function were observed in the pancreas. Changes like dilation of
      vein, unusual concentric arrangement of hepatocytes, and liver fibrosis were
      observed in the liver. Thickening of tubules and expansion of glomerulus were
      observed in kidneys. All these altered parameters were reversed close to normal
      condition upon treatment using idopyranose. The results show the antidiabetic
      potential of idopyranose. Interestingly, liver, kidney, and pancreatic sections
      of diabetic mice fed with the isolated 1, 2 di-substituted idopyranose showed
      regeneration of hepatocytes, nephrocytes, as well as beta-cells and acinar region
      appeared normal with increased numbers of beta-cells. To understand the probable
      mechanism of action of 1, 2 di-substituted idopyranose, we analyzed
      proinflammatory inducible nitric oxide synthase (iNOS) and nuclear factor-kappa B
      (NF-kappaB) expression by immunohistochemistry and the results showed an
      increased iNOS and NF-kappaB levels in streptozotocin-induced diabetic liver,
      kidney and pancreas. Such high iNOS and NF-kappaB levels were inhibited in 1, 2
      di-substituted idopyranose treated mice. The results suggest that 1, 2 di
      substituted idopyranose helps in the protection of hepatocytes, nephrocytes and
      pancreatic beta-cells probably by its action against NF-kappaB and iNOS mediated
      inflammation in streptozotocin-induced diabetes.

PMID- 20687130
TI  - Deposition of lead and cadmium released by cigarette smoke in dental structures
      and resin composite.
AB  - Cigarette smoke is a significant source of cadmium, lead, and toxic elements,
      which are absorbed into the human organism. In this context, the aim of this
      study was to investigate in vitro the presence of toxic elements, cadmium, and
      lead deriving from cigarette smoke in the resin composite, dentine, and dental
      enamel. Eight cylindrical specimens were fabricated from resin composite, bovine
      enamel, and root dentin fragments that were wet ground and polished with abrasive
      paper to obtain sections with 6-mm diameter and 2-mm thickness. All specimens
      were exposed to the smoke of 10 cigarettes/day during 8 days. After the
      simulation of the cigarette smoke, the specimens were examined with scanning
      electron microscopy (SEM) and the energy-dispersive X-ray analysis. In the
      photomicrographic analysis in SEM, no morphological alterations were found;
      however, the microanalysis identified the presence of cadmium, arsenic, and lead
      in the different specimens. These findings suggest that the deposition of these
      elements derived from cigarette smoke could be favored by dental structures and
      resin composite.

PMID- 20687131
TI  - Morphological changes in vero cells postinfection with dengue virus type-2.
AB  - Although no specific antiviral tablets or injections that can kill the dengue
      virus are currently available, adequate care and treatment could control its
      morbidity. Interaction of dengue virus to target cells could be an important
      feature for virus propagation. Ultrastructural analysis of this interaction was
      studied with vero cells. Vero cells were treated with Dengue virus type-2 at
      different time intervals at multiplicity of infection (m.o.i) < 10, m.o.i > 10,
      and m.o.i = 100. It was found that m.o.i < 10 is best to study morphological
      changes. At an m.o.i > 10 apoptosis occurs and at m.o.i. = 100, cell necrosis
      occurs. While studying morphological changes, it was found that at 30 min
      postinfection cells have morphology very similar to that of the control cells
      although some have irregular outline and show cytoplasmic projections and intense
      cytoplasmic vacuolization. After 1-12 hours postinfection (h.p.i), the nuclei ran
      from normal looking to diffuse. Nuclear membrane begins to disintegrate. Some
      nucleoli are difficult to be seen. The cytoplasm appears as a mottled, lumps
      diffuse mass distributed throughout the cytosol, with dense lysosomes and myelin
      figures, also in the mitochondria. In later hours (24 h.p.i), the intranuclear
      euchromatin is dispersed and heterochromatin forms peripheral clumps. The
      cytoplasmic processes are short and few in numbers. A proportion of damaged
      mitochondria with disrupted cristae appear, suggesting that dengue virus may
      induce mitochondrial dysfunction and nucleus and mitochondria may be the primary
      organelles helping in dissemination of virus.

PMID- 20687132
TI  - Improvement in cytoarchitectonic mapping by combining electrodynamic modeling
      with local orientation in high-resolution images of the cerebral cortex.
AB  - To detect changes of cortical cytoarchitectonics, digital images of cortical
      laminations are analyzed. Cortical regions are transformed into a rectangular
      grid for subsequent evaluations. Transformations are realized by stepwise
      scanning using perpendicular testlines. 3D cytoarchitectonic data of the human
      brain at a histological resolution are not available and 2D sections deliver
      partial information only. The problem is to find an optimal scanning-technique
      that introduces a minimum of distortions and noise by the transformation of the
      curvilinear cortex to a rectangular presentation. In the past this was solved by
      constructing testlines dependent on the outlined cortical contours only. An
      advanced approach was to model the contours as electrically charged surfaces and
      to use the resulting field lines as testlines. However, local information of cell
      distributions were not considered. Hence a novel hybrid approach was developed
      which is able to construct significantly better testlines in cortical images with
      mixtures of columnar rich (local orientation rich) and orientation poor parts of
      strongly curved and large regions of the cerebral cortex. The novel hybrid
      approach is based on the computer vision methods such as the structure tensor and
      constrained anisotropic diffusion. In addition, the introduction of projective
      transformations yields a significant improvement of cortical fingerprints,
      thereby offering the possibility for detecting weakly pronounced regions of
      cytoarchitectonic transitions. The statistical evaluation of the novel hybrid
      approach confirms robustness. This technique can be generalized and applied to
      different types of cerebral cortex with any kind and amount of local orientation
      information.

PMID- 20687133
TI  - Thermal unfolding studies show the disease causing F508del mutation in CFTR
      thermodynamically destabilizes nucleotide-binding domain 1.
AB  - Misfolding and degradation of CFTR is the cause of disease in patients with the
      most prevalent CFTR mutation, an in-frame deletion of phenylalanine (F508del),
      located in the first nucleotide-binding domain of human CFTR (hNBD1). Studies of
      (F508del)CFTR cellular folding suggest that both intra- and inter-domain folding
      is impaired. (F508del)CFTR is a temperature-sensitive mutant, that is, lowering
      growth temperature, improves both export, and plasma membrane residence times.
      Yet, paradoxically, F508del does not alter the fold of isolated hNBD1 nor did it
      seem to perturb its unfolding transition in previous isothermal chemical
      denaturation studies. We therefore studied the in vitro thermal unfolding of
      matched hNBD1 constructs +/-F508del to shed light on the defective folding
      mechanism and the basis for the thermal instability of (F508del)CFTR. Using
      primarily differential scanning calorimetry (DSC) and circular dichroism, we show
      for all hNBD1 pairs studied, that F508del lowers the unfolding transition
      temperature (T(m)) by 6-7 degrees C and that unfolding occurs via a kinetically
      controlled, irreversible transition in isolated monomers. A thermal unfolding
      mechanism is derived from nonlinear least squares fitting of comprehensive DSC
      data sets. All data are consistent with a simple three-state thermal unfolding
      mechanism for hNBD1 +/- F508del: N(+/-MgATP) <==> I(T)(+/-MgATP) -> A(T) ->
      (A(T))(n). The equilibrium unfolding to intermediate, I(T), is followed by the
      rate-determining, irreversible formation of a partially folded, aggregation
      prone, monomeric state, A(T), for which aggregation to (A(T))(n) and further
      unfolding occur with no detectable heat change. Fitted parameters indicate that
      F508del thermodynamically destabilizes the native state, N, and accelerates the
      formation of A(T).

PMID- 20687134
TI  - Mutagenicity and genotoxicity of PM2.5 issued from an urbano-industrialized area
      of Dunkerque (France).
AB  - Epidemiological studies have demonstrated the link between chronic exposure to
      particulate matter (PM), especially particles with an aerodynamic diameter lesser
      than 2.5 um (PM(2.5) ), and lung cancer. Mechanistic investigations focus on the
      contribution of the various genotoxicants adsorbed onto the particles, and more
      particularly on polycyclic aromatic hydrocarbons or nitroaromatics. Most of the
      previous studies dealing with genotoxic and/or mutagenic measurements were
      performed on organic extracts obtained from PM(2.5) collected in polluted areas.
      In contrast, we have evaluated genotoxic and mutagenic properties of urbano
      industrial PM(2.5) (PM) collected in Dunkerque (France). Thermally desorbed
      PM(2.5) (dPM) was also comparatively studied. Suspensions of PM and dPM (5-50 ug
      per plate) were tested in Salmonella tester strains TA98, TA102 and YG1041 +/-
      S9mix. Significant mutagenicity was observed for PM in YG1041 +/- S9 mix. In
      strain TA102 - S9mix, a slight, but not significant dose-response increase was
      observed, for both PM and dPM. Genotoxic properties of PM and dPM were evaluated
      by the measurement of (1) 8-OHdG in A549 cells and (2) bulky DNA adducts on A549
      cells and on human alveolar macrophages (AMs) in primary culture. A dose
      dependant formation of 8-OHdG adducts was observed on A549 cells for PM and dPM,
      probably mainly attributed to the core of the particles. Bulky DNA adducts were
      observed only in AMs after exposure to PM and dPM. In conclusion, using relevant
      exposure models, suspension of PM(2.5) induces a combination of DNA-interaction
      mechanisms, which could contribute to the induction of lung cancer in exposed
      populations.

PMID- 20687135
TI  - Efficacy of mulberry leaf tablets in patients with mild dyslipidemia.
AB  - Mulberry leaf is well known for its several biological effects. The purpose of
      this study was to evaluate the hypolipidemic effect of mulberry leaf in non
      diabetic patients with mild dyslipidemia. A within-subjects research design was
      conducted at the out-patient clinic in Thailand. Twenty-three patients who met
      the NCEP ATP III criteria guideline for dyslipidemia and failed a 4 week diet
      therapy were enrolled and assigned to receive three tablets of 280 mg mulberry
      leaf tablet three times a day before meals for a period of 12 weeks. Routine
      blood analyses including lipid parameters and liver function tests were performed
      every 4 weeks. At 4 and 8 weeks of mulberry leaf tablet therapy, triglyceride was
      significantly decreased by 10.2% (p < 0.05) and 12.5% (p < 0.05), respectively,
      from baseline. At the end of the study, total cholesterol, triglyceride and LDL
      were significantly decreased by 4.9% (p < 0.05), 14.1% (p < 0.05) and 5.6% (p <
      0.05), respectively, from baseline, whereas HDL was significantly increased by
      19.7% (p < 0.05). Even though some patients experienced side effects such as mild
      diarrhea (26%), dizziness (8.7%) or constipation and bloating (4.3%), mulberry
      leaf tablet therapy is still capable and safe in reducing cholesterol levels and
      enhancing HDL in patients with mild dyslipidemia.

PMID- 20687136
TI  - Comparative evaluation of two different Opuntia ficus-indica extracts for blood
      sugar lowering effects in rats.
AB  - Stems of Opuntia ficus-indica (L.) Mill. (OFI) are traditionally used in Mexico
      to treat diabetes mellitus. Less research data are available for combinations of
      stem and fruit preparations. The present study was designed to investigate the
      effects of an aqueous extract prepared from the cladodes and a proprietary
      stem/fruit skin-blend (stem/fruit skin ratio 75/25) of OFI on blood glucose and
      plasma insulin in normal rats. A dose finding study with the traditional cladode
      OFI extract revealed that maximum effects on blood glucose and insulin were
      observed after oral administration in a dose range of 6-176 mg/kg. The
      proprietary OFI blend significantly lowered blood glucose levels in the glucose
      tolerance test to a similar extent (p < 0.05 vs control) as the traditional
      aqueous cladode extract when administered in a dose of 6 mg/kg. In contrast to
      the aqueous extract, the proprietary blend significantly increased basal plasma
      insulin levels (p < 0.01 vs control) indicating a direct action on pancreatic
      beta cells. The results suggest that both OFI extracts exert hypoglycemic
      activities in rats in doses as low as 6 mg/kg but that the effects of the
      proprietary stem/fruit blend were more pronounced in our model.

PMID- 20687137
TI  - Regulation of adhesion molecules expression in TNF-alpha-stimulated brain
      microvascular endothelial cells by tanshinone IIA: involvement of NF-kappaB and
      ROS generation.
AB  - Pro-inflammatory cytokine-mediated expression of cell surface adhesion molecules
      plays a key role in endothelial cell injury, leading to vascular inflammation and
      the development of many cerebrovascular diseases. Thus, antiinflammatory agents
      targeting these adhesion molecules may represent potential drugs for the
      prevention and treatment of cerebrovascular diseases. The present study explored
      the effects of tanshinone IIA (Tan IIA), an active ingredient present in the
      Salvia miltiorrhiza root, on the expression of cellular adhesion molecules in TNF
      alpha-stimulated brain microvascular endothelial cells (BMVECs). Treatment with
      Tan IIA was found to suppress the expression of vascular cell adhesion molecule-1
      (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), resulting in inhibition
      of TNF-alpha-induced adhesion of neutrophils to BMVECs in a dose-dependent
      manner. In addition, Tan IIA significantly inhibited TNF-alpha-induced production
      of reactive oxygen species (ROS), which was accompanied by decreased
      malondialdehyde (MDA) levels. Treatment with Tan IIA also inhibited nuclear
      factor-kappa B (NF-kappaB) activation. Together, these results suggest that Tan
      IIA regulates TNF-alpha-induced expression of VCAM-1 and ICAM-1 through
      inhibition of NF-kappaB activation and ROS generation in BMVECs.

PMID- 20687138
TI  - Cued platform training reveals early development of directional responding among
      preweanling rats in the Morris water task.
AB  - Previous studies on the ontogeny of spatial learning report that rats younger
      than 19-21 days of age are incapable of learning the location of a platform
      relative to distal cues in the Morris water task. Here, we manipulated the
      spatial relationship of a cued platform to the pool and the distal visual room
      cues to investigate whether distal cues can control navigation among 16- to 24
      day-old rats. Rats were trained to navigate to a cued platform in a rich distal
      cue environment. During critical test trials, the pool was shifted to a
      different, overlapping position and the cued platform was placed either in the
      same absolute location in the room or the same relative location in the pool as
      during training. Rats aged 17 days and older exhibited a disruption in
      performance when the cued platform was in the absolute location but not the
      relative location, indicating that rats had learned the direction of the cued
      platform within the distal cue environment. These observations indicate that (1)
      information acquired from distal room cues influences navigation as early as 17
      days of age, (2) this distal cue information is preferentially used to guide
      navigation in a particular direction rather than to a precise place in the room,
      and (3) the directional nature of the influence of distal cues on navigation is
      invariant across development.

PMID- 20687139
TI  - EGR3 as a potential susceptibility gene for schizophrenia in Korea.
AB  - Early growth response (EGR) genes play critical roles in signal transduction in
      the brain, which is involved in neuronal activation, brain development, and
      synaptic plasticity. EGR genes, including EGR2, EGR3, and EGR4, showed
      significant association with schizophrenia in Japanese schizophrenic pedigrees.
      In particular, EGR3, which resides at the chromosomal location 8p21.3, was
      suggested to be a potential susceptibility gene in schizophrenia based on a study
      of Japanese cases. However, this requires further replication with an independent
      sample set. We investigated the association of the EGR3 and EGR2 genes, which
      were suggested as potential susceptibility genes for schizophrenia supported by
      both genetic association and postmortem brain expression studies, with
      schizophrenia in Korean patients. Along with 350 healthy individuals, 244
      schizophrenic patients were analyzed. Among the four examined single-nucleotide
      polymorphisms (SNPs) of EGR3 (rs1008949, rs7009708, rs35201266, and rs3750192),
      SNP rs35201266 in intron 1 of the EGR3 gene showed a significant association with
      schizophrenia (P = 0.0008, chi(2) = 11.156, OR = 1.493), which withstands
      multiple testing correction. In addition, the "T-G-C-G" haplotype of EGR3 was
      under-represented in the patients with schizophrenia (P = 0.0073, chi(2) = 7.188,
      OR = 0.697). However, an association between the SNPs of EGR2 (rs2295814 and
      rs2297488) and schizophrenia was not found. These findings are consistent with
      the previous genetic association of the EGR3 gene in Japanese cohorts, which is
      the first replication concerning the association of EGR3 with schizophrenia in an
      independent cohort. Taken together, EGR3 could be suggested as a compelling
      susceptibility gene in schizophrenia.

PMID- 20687140
TI  - Biomass production of hairy roots of Artemisia annua and Arachis hypogaea in a
      scaled-up mist bioreactor.
AB  - Hairy roots have the potential to produce a variety of valuable small and large
      molecules. The mist reactor is a gas phase bioreactor that has shown promise for
      low-cost culture of hairy roots. Using a newer, disposable culture bag, mist
      reactor performance was studied with two species, Artemisia annua L. and Arachis
      hypogaea (peanut), at scales from 1 to 20 L. Both species of hairy roots when
      grown at 1 L in the mist reactor showed growth rates that surpassed that in shake
      flasks. From the information gleaned at 1 L, Arachis was scaled further to 4 and
      then 20 L. Misting duty cycle, culture medium flow rate, and timing of when flow
      rate was increased were varied. In a mist reactor increasing the misting cycle or
      increasing the medium flow rate are the two alternatives for increased delivery
      of liquid nutrients to the root bed. Longer misting cycles beyond 2-3 min were
      generally deemed detrimental to growth. On the other hand, increasing the medium
      flow rate to the sonic nozzle especially during the exponential phase of root
      growth (weeks 2-3) was the most important factor for increasing growth rates and
      biomass yields in the 20 L reactors. A. hypogaea growth in 1 L reactors was u =
      0.173 day(-1) with biomass yield of 12.75 g DW L(-1). This exceeded that in shake
      flasks at u = 0.166 day(-1) and 11.10 g DW L(-1). Best growth rate and biomass
      yield at 20 L was u = 0.147 and 7.77 g DW L(-1), which was mainly achieved when
      medium flow rate delivery was increased. The mist deposition model was further
      evaluated using this newer reactor design and when the apparent thickness of
      roots (+hairs) was taken into account, the empirical data correlated with model
      predictions. Together these results establish the most important conditions to
      explore for future optimization of the mist bioreactor for culture of hairy
      roots.

PMID- 20687141
TI  - Tailor-made nanometer-scale patterns of photo-switchable Prussian blue analogues.

PMID- 20687142
TI  - Monolithic complementary inverters based on organic single crystals.

PMID- 20687143
TI  - Water stable Zr-benzenedicarboxylate metal-organic frameworks as photocatalysts
      for hydrogen generation.
AB  - The Zr-containing metal-organic frameworks (MOFs) formed by terephthalate (UiO
      66) and 2-aminoterephthalate ligands [UiO-66(NH(2))] are two notably water
      resistant MOFs that exhibit photocatalytic activity for hydrogen generation in
      methanol or water/methanol upon irradiation at wavelength longer than 300 nm. The
      apparent quantum yield for H(2) generation using monochromatic light at 370 nm in
      water/methanol 3:1 was of 3.5% for UiO-66(NH(2)). Laser-flash photolysis has
      allowed detecting for UiO-66 and UiO-66(NH(2)) the photochemical generation of a
      long lived charge separated state whose decay is not complete 300 MUs after the
      laser flash. Our finding and particularly the influence of the amino group
      producing a bathochromic shift in the optical spectrum without altering the
      photochemistry shows promises for the development of more efficient MOFs for
      water splitting.

PMID- 20687144
TI  - A carbon nanohorn-porphyrin supramolecular assembly for photoinduced electron
      transfer processes.
AB  - A supramolecular assembly of zinc porphyrin-carbon nanohorns (CNHs) was
      constructed in a polar solvent. An ammonium cation was covalently connected to
      the CNH through a spacer (sp) (CNH-sp-NH(3)(+)) and bound to a crown ether linked
      to a zinc porphyrin (Crown-ZnP). Nanohybrids CNH-sp-NH(3)(+);Crown-ZnP and CNH-sp
      NH(3)(+) were characterized by several techniques, such as high-resolution
      transmission electron microscopy, thermogravimetric analysis, X-ray photoelectron
      spectroscopy, and Raman spectroscopy. The photoinduced electron-transfer
      processes of the nanohybrids have been confirmed by using time-resolved
      absorption and fluorescence measurements by combining the steady-state spectral
      data. Fluorescence quenching of the ZnP unit by CNH-sp-NH(3)(+) has been
      observed, therefore, photoinduced charge separation through the excited singlet
      state of the ZnP unit is suggested for the hybrid material, CNH-sp-NH(3)(+);Crown
      ZnP. As transient absorption spectral experiments reveal the formation of the
      radical cation of the ZnP unit, electron generation is suggested as a counterpart
      of the charge-separation on the CNHs; such an electron on the CNHs is further
      confirmed by migrating to the hexylviologen dication (HV(2+)). Accumulation of
      the electron captured from HV(*+) is observed as electron pooling in solution in
      the presence of a hole-shifting reagent. Photovoltaic performance with moderate
      efficiency is confirmed for CNH-sp-NH(3)(+);Crown-ZnP deposited onto
      nanostructured SnO(2) films.

PMID- 20687145
TI  - Pt-NiCo nanostructures with facilitated electrocatalytic activities for sensitive
      determination of intracellular thiols with long-term stability.
AB  - A Pt-NiCo nanomaterial has been synthesized for developing the sensitive
      electrochemical determination of biological thiols that include L-cysteine
      (CySH), homocysteine (HCySH), and gluthione (GSH) with high sensitivity and long
      term stability, in which the Pt nanoparticles are well supported on amorphous
      NiCo nanofilms. The electrochemical oxidation of thiols has been successfully
      facilitated on the optimized Pt-NiCo nanostructures, that is, two oxidation peaks
      of CySH have been clearly observed at potentials of +0.06 and +0.45 V. The
      experimental results demonstrate that the first peak for CySH oxidation may be
      attributed to a direct oxidation from CySH to L-cystine (CySSCy), whereas the
      second peak possibly results from a sequential oxidation from CySSCy to cysteic
      acid (CySO(3)H), together with a direct oxidation of CySH into CySO(3)H. The
      enhanced electrocatalytic activities at the Pt(23)-NiCo nanostructures have
      provided a methodology to determine thiols at a very low potential of 0.0 V with
      relatively high sensitivity (637 nA MUM cm(-2)), a low detection limit (20 nM),
      and a broad linear range. The striking analytical performance, together with the
      characteristic properties of the Pt-NiCo nanomaterial itself, including long-term
      stability and strong antipoisoning ability, has established a reliable and
      durable approach for the detection of thiols in liver cancer cells, Hep G2.

PMID- 20687146
TI  - Synthesis and conformational characterisation of hexameric beta-peptide foldamers
      by using double POAC spin labelling and cw-EPR.
AB  - A selected set of terminally protected beta-hexapeptides, each containing two
      nitroxide-based (3R,4R)-4-amino-1-oxyl-2,2,5,5-tetramethylpyrrolidine-3
      carboxylic acid (POAC) residues combined with four (1S,2S)-2-aminocyclopentane-1
      carboxylic acid (ACPC) residues, was synthesised by using solution methods and
      was fully characterised. The two POAC residues are separated in the sequences by
      different numbers of intervening ACPC residues. The conformational features of
      the doubly spin-labelled beta-hexapeptides were examined in chloroform by FTIR
      absorption and continuous-wave electron paramagnetic resonance spectroscopic
      techniques. In particular, the biradical exchange coupling (J) between two POAC
      residues within each peptide indicates unambiguously that the secondary structure
      overwhelmingly adopted is the 12-helix. Taken together, these results support the
      view that POAC is an excellent beta-amino acid for exploring this type of helical
      conformation in doubly labelled beta-peptides.

PMID- 20687147
TI  - Copper-catalysed domino silylative aldol reaction leading to stereocontrolled
      chiral quaternary carbons.

PMID- 20687148
TI  - New chiral calixsalen chromium complexes: recyclable asymmetric catalysts.
AB  - A chiral N,N'-bis(salicylidene)ethylenediamine (salen) polymer has been prepared
      by a condensation reaction between a thiophenedisalicyladehyde derivative and
      (S,S)-cyclohexane-1,2-diamine. This polymeric compound was demonstrated to
      possess a cyclic structure with two to five repetitive units. The addition of
      chromium(II) salts led to the generation of a chiral catalyst that could be
      recovered as an insoluble powder. The performance of this new calixsalen-type
      catalyst was examined in various transformations, particularly in its ability to
      promote nucleophilic epoxide ring opening under heterogeneous conditions. The
      target products were obtained in high yields and with improved selectivity
      compared with those obtained by using analogous linear polymers. The arrangement
      of the catalytic sites in the cyclic structure is probably more suitable for the
      necessary cooperative bimetallic pathway of this demanding reaction. The catalyst
      could be successfully recycled. This approach represents the first use of
      calixsalen complexes under heterogeneous catalytic conditions.

PMID- 20687149
TI  - Oxidative degradation of zinc porphyrin in comparison with its iron analogue.

PMID- 20687150
TI  - Neutral and anionic transition-metal-base-stabilized metalloborylene complexes.

PMID- 20687151
TI  - Tunable diastereoselection of biased rigid systems by Lewis acid induced
      conformational effects: a rationalization of the vinylation of cyclic nitrones en
      route to polyhydroxylated pyrrolidines.
AB  - The diastereofacial selection in addition reactions to biased rigid systems can
      be modulated by the action of Lewis acids. As an example, the stereoselectivity
      of the nucleophilic addition of vinyl magnesium bromide (VMB) to cyclic nitrones
      in the presence of diethylaluminum chloride (DEAC) shows a strong dependence on
      the temperature and the carbon substituent adjacent at the reaction center; it is
      remarkable that whereas a high selectivity is obtained at higher temperatures, in
      the presence of DEAC, a trend to invert the stereochemical course of the reaction
      is observed at lower temperatures, provided the substituent at C3 of the
      pyrrolidine ring allows delivery of the vinyl moiety. This behavior and
      difference in selectivity is to be attributed to the high conformational barriers
      of the intermediate nitrone-DEAC-VMB complex. A clear inversion of the
      selectivity is observed at -78 degrees C for the reaction of the nitrone
      protected as an O-methyl derivative. The present study provides a rationalization
      for the stereocontrolled addition of nucleophiles to rigid systems (cyclic
      nitrones).

PMID- 20687152
TI  - Evaluation of the chemical reactions from two electrogenerated species in
      picoliter volumes by scanning electrochemical microscopy.
AB  - The volume created by the positioning of two scanning electrochemical microscope
      (SECM) probes (tip and substrate) at a micrometric distance defines a "picoliter
      beaker" where homogeneous electron-transfer reactions are studied. The SECM is
      used to concurrently electrogenerate in situ two reactive species and to evaluate
      the possibility of detecting their reactivity. Two reaction cases are studied:
      the first, called the "reversible case", occurs when the electrochemically
      generated species at the substrate electrode can also react at the tip to yield
      the same product as the reaction in the gap. The second case, named the
      "irreversible case", occurs when the electrochemically generated species at the
      substrate are not able to react at the tip. Digital simulations are performed and
      compared to experimental studies. These show that an unusual compensation between
      collection and feedback effects render the analysis inapplicable in the
      "reversible case". The "irreversible case" is shown experimentally.

PMID- 20687153
TI  - Effects of the combination treatment of raloxifene and alendronate on the
      biomechanical properties of vertebral bone.
AB  - Raloxifene (RAL) and alendronate (ALN) improve the biomechanical properties of
      bone by different mechanisms. The goal here was to investigate the effects of
      combination treatment of RAL and ALN on the biomechanical properties of vertebral
      bone. Six-month-old Sprague-Dawley rats (n = 80) were randomized into five
      experimental groups (sham, OVX, OVX + RAL, OVX + ALN, and OVX + RAL + ALN; n =
      16/group). Following euthanization, structural and derived material biomechanical
      properties of vertebral bodies were assessed. Density and dynamic
      histomorphometric measurements were made on cancellous bone. The results
      demonstrate that the structural biomechanical properties of vertebral bone are
      improved with the combination treatment. Stiffness and ultimate load of the OVX +
      RAL and OVX + ALN groups were significantly lower than those of sham animals, but
      the combination treatment with RAL + ALN was not significantly different from
      sham. Furthermore, the OVX + RAL + ALN group was the only agent-treated group in
      which the ultimate load was significantly higher than that in OVX animals (p <
      .05). Cancellous bone fractional volume (BV/TV(canc)) and bone mineral density
      (aBMD) also were improved with the combination treatment. BV/TV(canc) of the OVX
      + RAL + ALN group was 6.7% and 8.7% greater than that of the OVX + RAL (p < .05)
      and OVX + ALN (p < .05) groups, respectively. Areal BMD of the OVX + RAL or OVX +
      ALN groups was not significantly different from that in OVX animals, but the
      value in animals undergoing combination treatment was significantly higher than
      that in OVX or OVX + RAL animals alone and not significantly different from that
      in sham-operated animals. Turnover rates of both the RAL + ALN and ALN alone
      groups were lower than in the RAL-treated alone group (p < .05). We conclude that
      the combination treatment of raloxifene and alendronate has beneficial effects on
      bone volume, resulting in improvement in the structural properties of vertebral
      bone.

PMID- 20687154
TI  - BMD regulation on mouse distal chromosome 1, candidate genes, and response to
      ovariectomy or dietary fat.
AB  - The distal end of mouse chromosome 1 (Chr 1) harbors quantitative trait loci
      (QTLs) that regulate bone mineral density (BMD) and share conserved synteny with
      human chromosome 1q. The objective of this article was to map this mouse distal
      Chr 1 region and identify gene(s) responsible for BMD regulation in females. We
      used X-ray densitometry [ie, dual-energy X-ray Absorptiometry (DXA), micro
      computed tomography (uCT), and peripheral quantitative computed tomography
      (pQCT)] to phenotype a set of nested congenic strains constructed from C57BL/6BmJ
      (B6/Bm) and C3H/HeJ (C3H) mice to map the region associated with the BMD QTL. The
      critical region has been reduced to an interval of 0.152 Mb that contributes to
      increased BMD when C3H alleles are present. Histomorphometry and osteoblast
      cultures indicated that increased osteoblast activity was associated with
      increased BMD in mouse strains with C3H alleles in this critical region. This
      region contains two genes, Aim2, which binds with cytoplasmic dsDNA and results
      in apoptosis, and AC084073.22, a predicted gene of unknown function. Ovariectomy
      induced bone loss in the B6/Bm progenitor and the three congenic strains
      regardless of the alleles present in the critical BMD region. High dietary fat
      treatment (thought to suppress distal Chr 1 QTL for BMD in mice) did not induce
      bone loss in the congenics carrying C3H alleles in the critical 0.152 Mb carrying
      the AIM2 and AC084073.22 genes. Gene expression studies in whole bone of key
      congenics showed differential expression of AC084073.22 for strains carrying
      B6/Bm versus C3H alleles but not for Aim2. In conclusion, our data suggest that
      osteoblasts are the cellular target of gene action and that AC084073.22 is the
      best candidate for female BMD regulation in the distal region of mouse Chr 1.

PMID- 20687155
TI  - Vitamin C promotes widespread yet specific DNA demethylation of the epigenome in
      human embryonic stem cells.
AB  - Vitamin C (ascorbate) is a widely used medium supplement in embryonic stem cell
      culture. Here, we show that ascorbate causes widespread, consistent, and
      remarkably specific DNA demethylation of 1,847 genes in human embryonic stem
      cells (hESCs), including important stem cell genes, with a clear bias toward
      demethylation at CpG island boundaries. We show that a subset of these DNA
      demethylated genes displays concomitant gene expression changes and that the
      position of the demethylated CpGs relative to the transcription start site is
      correlated to such changes. We further show that the ascorbate-demethylated gene
      set not only overlaps with gene sets that have bivalent marks, but also with the
      gene sets that are demethylated during differentiation of hESCs and during
      reprogramming of fibroblasts to induced pluritotent stem cells (iPSCs). Our data
      thus identify a novel link between ascorbate-mediated signaling and specific
      epigenetic changes in hESCs that might impact on pluripotency and reprogramming
      pathways.

PMID- 20687157
TI  - Sigma receptors and their ligands in cancer biology: overview and new
      perspectives for cancer therapy.
AB  - A large number of drugs are known to bind with high affinity to sigma receptors
      (sigma-Rs) and have been used in the clinic to treat mental disorders for many
      years. However, recent publications highlighting sigma-R overexpression in many
      cancer tissues suggest potential applications for sigma-R ligands in cancer
      diagnosis and therapy. The present review focuses on the involvement of sigma-Rs
      in cancer biology and the potential therapeutic contributions of their
      pharmacologic ligands in oncology. After summarizing the current and general
      knowledge regarding sigma-Rs, we detail data reported in the particular context
      of oncology. We then investigate the potential and specific signal transduction
      pathways and mechanisms involved in the actions of sigma-R ligands in cancer
      biology. These processes include modulations of (1) the plasma membrane and lipid
      raft components, (2) intracellular calcium levels, (3) cytoskeletal protein
      functions, and (4) endoplasmic reticulum stress. Finally, we conclude by
      speculating on the roles of sigma-R overexpression and sigma-R ligands in cancer
      biology and offer perspectives on cancer therapy.

PMID- 20687156
TI  - Proteomic analysis of Sox2-associated proteins during early stages of mouse
      embryonic stem cell differentiation identifies Sox21 as a novel regulator of stem
      cell fate.
AB  - Small increases in the levels of master regulators, such as Sox2, in embryonic
      stem cells (ESC) have been shown to promote their differentiation. However, the
      mechanism by which Sox2 controls the fate of ESC is poorly understood. In this
      study, we employed multidimensional protein identification technology and
      identified >60 nuclear proteins that associate with Sox2 early during ESC
      differentiation. Gene ontology analysis of Sox2-associated proteins indicates
      that they participate in a wide range of processes. Equally important, a
      significant number of the Sox2-associated proteins identified in this study have
      been shown previously to interact with Oct4, Nanog, Sall4, and Essrb. Moreover,
      we examined the impact of manipulating the expression of a Sox2-associated
      protein on the fate of ESC. Using ESC engineered for inducible expression of
      Sox21, we show that ectopic expression of Sox21 in ESC induces their
      differentiation into specific cell types, including those that express markers
      representative of neurectoderm and heart development. Collectively, these studies
      provide new insights into the range of molecular processes through which Sox2 is
      likely to influence the fate of ESC and provide further support for the
      conclusion that the expression of Sox proteins in ESC must be precisely
      regulated. Importantly, our studies also argue that Sox2, along with other
      pluripotency-associated transcription factors, is woven into highly
      interconnected regulatory networks that function at several levels to control the
      fate of ESC.

PMID- 20687158
TI  - ROS receptor tyrosine kinase: a new potential target for anticancer drugs.
AB  - ROS kinase is one of the last two remaining orphan receptor tyrosine kinases with
      an as yet unidentified ligand. The normal functions of human ROS kinase in
      different body tissues have not been fully identified so far. However, the
      ectopic expression, as well as the production of variable mutant forms of ROS
      kinase has been reported in a number of cancers, such as glioblastoma multiforme,
      and non-small cell lung cancer, suggesting a role for ROS kinase in deriving such
      tumors. It is thought also that c-ROS gene may have a role in some cardiovascular
      diseases, and the fact that homozygous male mice targeted against c-ROS gene are
      healthy but infertile, has inspired researchers to think about ROS inhibition as
      a method for development of new male contraceptives. The recent discovery of new
      selective and potent inhibitors for ROS kinase, along with the development of new
      specific diagnostic methods for the detection of ROS fusion proteins, raises the
      importance of using these selective inhibitors for targeting ROS mutations as a
      new method for treatment of cancers harboring such genes. This review focuses on
      the ectopic expression of ROS and its fusion proteins in different cancer types
      and highlights the importance of targeting these proteins for treatment of
      substantial cancers. It describes also the recent advances in the field of ROS
      kinase inhibition, and the potential clinical applications of ROS kinase
      inhibitors.

PMID- 20687159
TI  - Prolonged survival and phenotypic correction of Akp2(-/-) hypophosphatasia mice
      by lentiviral gene therapy.
AB  - Hypophosphatasia (HPP) is an inherited systemic skeletal disease caused by
      mutations in the gene encoding the tissue-nonspecific alkaline phosphatase
      (TNALP) isozyme. The clinical severity of HPP varies widely, with symptoms
      including rickets and osteomalacia. TNALP knockout (Akp2(-/-)) mice
      phenotypically mimic the severe infantile form of HPP; that is, TNALP-deficient
      mice are born with a normal appearance but die by 20 days of age owing to growth
      failure, hypomineralization, and epileptic seizures. In this study, a lentiviral
      vector expressing a bone-targeted form of TNALP was injected into the jugular
      vein of newborn Akp2(-/-) mice. We found that alkaline phosphatase activity in
      the plasma of treated Akp2(-/-) mice increased and remained at high levels
      throughout the life of the animals. The treated Akp2(-/-) mice survived for more
      than 10 months and demonstrated normal physical activity and a healthy
      appearance. Epileptic seizures were completely inhibited in the treated Akp2(-/-)
      mice, and X-ray examination of the skeleton showed that mineralization was
      significantly improved by the gene therapy. These results show that severe
      infantile HPP in TNALP knockout mice can be treated with a single injection of
      lentiviral vector during the neonatal period.

PMID- 20687160
TI  - Reproductive system of female scorpion: a partial review.
AB  - The female scorpion ovariuterus was examined in 10 scorpion species belonging to
      five families: Buthidae, Vaejovidae, Scorpionidae, Urodacidae, and
      Diplocentridae. Two main patterns of development are known in scorpions: (1) The
      apoikogenic type with an ovariuterus containing yolk-rich eggs housed in
      follicles. This type is found in many scorpion taxa (largely buthids). A peculiar
      case of apoikogenic ovariuterus is a "beaded" ovariuterus where most of the ova's
      embryogenesis takes place inside the ovariuterus rather than on pedicels situated
      on the external wall of the ovariuterus as in most buthids. This type is found in
      a few scorpion species. (2) The katoikogenic type with an ovariuterus where the
      embryo develops in a diverticulum composed of four parts: a stalk (pedicel), a
      thickened collar, a conical portion containing the ovum, and an appendix
      containing the oral feeding apparatus where the embryos' chelicerae grip a "teat"
      like structure, described in four families: Hemiscorpiidae, Scorpionidae,
      Urodacidae, and Diplocentridae. There are three kinds of diverticulae: small
      rudimentary finger-like diverticulae, embryonic (ED) large projections, and
      postpartum diverticulae (PPD) empty diverticulae, which are remnants after
      parturition. The subject is reviewed and its bearing on reproduction in scorpions
      are discussed.

PMID- 20687161
TI  - Astacin proteases cleave dentin sialophosphoprotein (Dspp) to generate dentin
      phosphoprotein (Dpp).
AB  - Dentin sialophosphoprotein (Dspp) is critical for proper dentin biomineralization
      because genetic defects in DSPP cause dentin dysplasia type II and dentinogenesis
      imperfecta types II and III. Dspp is processed by proteases into smaller
      subunits; the initial cleavage releases dentin phosphoprotein (Dpp). We incubated
      fluorescence resonance energy transfer (FRET) peptides containing the amino acid
      context of the Dpp cleavage site (YEFDGKSMQGDDPN, designated Dspp-FRET) or a
      mutant version of that context (YEFDGKSIEGDDPN, designated mutDspp-FRET) with BMP
      1, MEP1A, MEP1B, MMP-2, MMP-8, MMP-9, MT1-MMP, MT3-MMP, Klk4, MMP-20, plasmin, or
      porcine Dpp and characterized the peptide cleavage products. Only BMP-1, MEP1A,
      and MEP1B cleaved Dspp-FRET at the G-D peptide bond that releases Dpp from Dspp
      in vivo. We isolated Dspp proteoglycan from dentin power and incubated it with
      the three enzymes that cleaved Dspp-FRET at the G-D bond. In each case, the
      released Dpp domain was isolated, and its N-terminus was characterized by Edman
      degradation. BMP-1 and MEP1A both cleaved native Dspp at the correct site to
      generate Dpp, making both these enzymes prime candidates for the protease that
      cleaves Dspp in vivo. MEP1B was able to degrade Dpp when the Dpp was at
      sufficiently high concentration to deplete free calcium ion concentration.
      Immunohistochemistry of developing porcine molars demonstrated that astacins are
      expressed by odontoblasts, a result that is consistent with RT-PCR analyses. We
      conclude that during odontogenesis, astacins in the predentin matrix cleave Dspp
      before the DDPN sequence at the N-terminus of Dpp to release Dpp from the parent
      Dspp protein.

PMID- 20687162
TI  - Sample size determination in clinical trials with multiple co-primary binary
      endpoints.
AB  - Clinical trials often employ two or more primary efficacy endpoints. One of the
      major problems in such trials is how to determine a sample size suitable for
      multiple co-primary correlated endpoints. We provide fundamental formulae for the
      calculation of power and sample size in order to achieve statistical significance
      for all the multiple primary endpoints given as binary variables. On the basis of
      three association measures among primary endpoints, we discuss five methods of
      power and sample size calculation: the asymptotic normal method with and without
      continuity correction, the arcsine method with and without continuity correction,
      and Fisher's exact method. For all five methods, the achieved sample size
      decreases as the value of association measure increases when the effect sizes
      among endpoints are approximately equal. In particular, a high positive
      association has a greater effect on the decrease in the sample size. On the other
      hand, such a relationship is not very strong when the effect sizes are different.

PMID- 20687164
TI  - Elective radiotherapy or neck dissection for CT-staged T1-2N0 oral tongue cancer.

PMID- 20687163
TI  - Integrated biophysical studies implicate partial unfolding of NBD1 of CFTR in the
      molecular pathogenesis of F508del cystic fibrosis.
AB  - The lethal genetic disease cystic fibrosis is caused predominantly by in-frame
      deletion of phenylalanine 508 in the cystic fibrosis transmembrane conductance
      regulator (CFTR). F508 is located in the first nucleotide-binding domain (NBD1)
      of CFTR, which functions as an ATP-gated chloride channel on the cell surface.
      The F508del mutation blocks CFTR export to the surface due to aberrant retention
      in the endoplasmic reticulum. While it was assumed that F508del interferes with
      NBD1 folding, biophysical studies of purified NBD1 have given conflicting results
      concerning the mutation's influence on domain folding and stability. We have
      conducted isothermal (this paper) and thermal (accompanying paper) denaturation
      studies of human NBD1 using a variety of biophysical techniques, including
      simultaneous circular dichroism, intrinsic fluorescence, and static light
      scattering measurements. These studies show that, in the absence of ATP, NBD1
      unfolds via two sequential conformational transitions. The first, which is
      strongly influenced by F508del, involves partial unfolding and leads to
      aggregation accompanied by an increase in tryptophan fluorescence. The second,
      which is not significantly influenced by F508del, involves full unfolding of
      NBD1. Mg-ATP binding delays the first transition, thereby offsetting the effect
      of F508del on domain stability. Evidence suggests that the initial partial
      unfolding transition is partially responsible for the poor in vitro solubility of
      human NBD1. Second-site mutations that increase the solubility of isolated
      F508del-NBD1 in vitro and suppress the trafficking defect of intact F508del-CFTR
      in vivo also stabilize the protein against this transition, supporting the
      hypothesize that it is responsible for the pathological trafficking of F508del
      CFTR.

PMID- 20687166
TI  - Open organ preservation surgery of the larynx: Experience of Istituto Nazionale
      Tumori of Milan.
AB  - BACKGROUND: The purpose of the present study was to report the oncological and
      functional results of our experience in open organ preservation surgery of the
      larynx. METHODS: Between 1978 and 2006, 140 patients were treated with organ
      preservation surgery of the larynx. Feeding tube and tracheotomy duration,
      surgical infection, fistulae, and pneumonia were recorded. RESULTS: Most patients
      were treated with supraglottic laryngectomies. Thirteen patients (9%) experienced
      a faringo-cutaneous fistula, 23 (16%) presented with a surgical site infection,
      and 6 (4%) developed pneumonia. Tracheotomy was maintained for a median period of
      47 days in patients who did not receive postoperative radiotherapy (RT) and 140
      days in patients who did. Eight (6%) total laryngectomies were performed because
      of oncological and functional reasons. Tube feeding continued for an average
      period of 34 days. Patients with squamous cell carcinoma (SCC) had 5-year disease
      free survival (DFS) of 83.6%. CONCLUSION: Open organ preservation surgery proved
      oncologically effective with good functional outcome and acceptable
      complications.

PMID- 20687167
TI  - Could teriparatide be the treatment for osteonecrosis of the jaws?

PMID- 20687168
TI  - Overall and cause-specific survival for patients undergoing lobectomy, near
      total, or total thyroidectomy for differentiated thyroid cancer.
AB  - BACKGROUND: The extent of surgery for well-differentiated thyroid cancer remains
      controversial. The purpose of this study was to evaluate the type of resection,
      age, T classification, nodal status, tumor size, and year of diagnosis for
      overall survival (OS) and cause-specific survival (CSS) using a large database.
      METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database,
      23,605 subjects were identified with papillary or follicular thyroid cancer
      between 1983 and 2002. OS and CSS were estimated, and outcomes for local
      excision, lobectomy, near-total thyroidectomy, or total thyroidectomy were
      compared. RESULTS: Ten-year OS and CSS by surgery were: total thyroidectomy,
      90.4% and 96.8%, respectively; near-total thyroidectomy, 89.5% and 96.6%,
      respectively; and lobectomy, 90.8% and 98.6%, respectively. Controlling for risk
      factors, near-total thyroidectomy was inferior to total thyroidectomy for OS
      (hazard ratio [HR] 1.21; p = .019) and CSS (HR 1.39; p = .019). Age, T3/T4
      disease, positive nodes, and tumor size were associated with poorer outcomes.
      CONCLUSION: Total thyroidectomy resulted in improved survival. Therapy should be
      individualized, accounting for potential complications and recurrence patterns.

PMID- 20687170
TI  - Salivary stress biomarker levels during speech in patients with maxillectomy
      defect.
AB  - BACKGROUND: After resection of maxillofacial tumors, severe functional problems
      related to mastication, deglutition, and speech are observed in addition to the
      changes in appearance and psychosocial functioning. Although speech outcome is
      recovered with prosthetic treatments, patients sometimes complain of continued
      dissatisfaction with their speech. The purpose of this study was to evaluate the
      potential dissatisfaction of patients with maxillectomy defects during speech.
      METHODS: Sixteen patients with maxillary obturator were compared with a matched
      control group. Functional improvement by the maxillofacial prosthesis was
      confirmed using a speech intelligibility test, a chewing function score, and
      visual analogue scale on subjective satisfaction. Cortisol and chromogranin A
      (CgA) were evaluated after prescribed speech tasks. RESULTS: CgA in patients with
      maxillectomy defects was significantly higher than that in the control group (p <
      .05), even after the functional improvement by maxillofacial prosthesis.
      CONCLUSION: It was revealed that patients with maxillectomy defects have
      significant psychological stresses during speech, even when their maxillofacial
      prosthesis resulted in successful functional improvement.

PMID- 20687171
TI  - Predictive value of high Ki-67 expression in stage I oral squamous cell carcinoma
      specimens after primary surgery.
AB  - BACKGROUND: Until now prognostic evaluation for patients with oral squamous cell
      carcinoma (OSCC) remains difficult. Thus, the aim of the present study was to
      ascertain the value of Ki-67 expression in predicting locoregional recurrence in
      OSCC. METHODS: In a large, homogeneous study population consisting of 166
      patients with OSCC exclusively treated with primary surgery, expression of Ki-67
      was investigated by immunohistochemistry. RESULTS: We report that high
      proliferation significantly correlated to a higher risk of locoregional
      recurrence in stage I OSCC patients (p = .029). Carcinomas with a Ki-67 labeling
      index above the median showed a mean time to recurrence of 42 months, whereas
      mean time to recurrence was 55 months for those tumors below the median (p =
      .017). CONCLUSIONS: This study provides the evidence of a predictive value of Ki
      67 expression in stage I OSCC. Therefore, Ki-67 expression level could be used to
      identify a subgroup of surgically treated patients with stage I OSCC who might
      benefit from treatment intensification.

PMID- 20687172
TI  - Evaluating novel agent effects in multiple-treatments meta-regression.
AB  - Multiple-treatments meta-analyses are increasingly used to evaluate the relative
      effectiveness of several competing regimens. In some fields which evolve with the
      continuous introduction of new agents over time, it is possible that in trials
      comparing older with newer regimens the effectiveness of the latter is
      exaggerated. Optimism bias, conflicts of interest and other forces may be
      responsible for this exaggeration, but its magnitude and impact, if any, needs to
      be formally assessed in each case. Whereas such novelty bias is not identifiable
      in a pair-wise meta-analysis, it is possible to explore it in a network of trials
      involving several treatments. To evaluate the hypothesis of novel agent effects
      and adjust for them, we developed a multiple-treatments meta-regression model
      fitted within a Bayesian framework. When there are several multiple-treatments
      meta-analyses for diverse conditions within the same field/specialty with similar
      agents involved, one may consider either different novel agent effects in each
      meta-analysis or may consider the effects to be exchangeable across the different
      conditions and outcomes. As an application, we evaluate the impact of modelling
      and adjusting for novel agent effects for chemotherapy and other non-hormonal
      systemic treatments for three malignancies. We present the results and the impact
      of different model assumptions to the relative ranking of the various regimens in
      each network. We established that multiple-treatments meta-regression is a good
      method for examining whether novel agent effects are present and estimation of
      their magnitude in the three worked examples suggests an exaggeration of the
      hazard ratio by 6 per cent (2-11 per cent).

PMID- 20687173
TI  - Toward a concept of stretch coupling in smooth muscle: a thesis by Lars Thuneberg
      on contractile activity in neonatal interstitial cells of Cajal.
AB  - The hypothesis was put forward by Thuneberg that rhythmically contracting
      interstitial cells of Cajal (ICC) were sensing stretch of the musculature and
      that this information was transmitted to smooth muscle cells via peg and socket
      contacts. The present study provides the evidence for the contractile nature of
      ICC as perceived by Thuneberg. The contractile activity is shown by video frame
      subtraction and by tracking areas of interest in sequential video frames.
      Thuneberg used neonatal ICC in culture maintained between two coverslips thereby
      allowing growth factors to quickly reach optimal concentrations. Contractions of
      ICC were seen to precede smooth muscle contractions. In addition, strong
      contractions were observed solely in branches of ICC. It is hoped that this
      communication will stimulate discussion about the contractile nature of ICC and
      that this phenomenon will eventually find its place amongst the physiological
      properties of the ICC networks of the gut musculature.

PMID- 20687174
TI  - The cutaneous microvascular architecture of human diabetic toe studied by
      corrosion casting and scanning electron microscopy analysis.
AB  - In this morphological study, we report on the three-dimensional microvascular
      architecture constituting the toes of a patient affected by diabetic
      microangiopathy. We applied corrosion casting (CC) technique to the toes of a
      patient affected by Type 2 diabetes, who underwent surgery for explantation of
      inferior left limb due to necrotic processes of soft tissues. The toes of a foot
      traumatically explanted in a motorcycle accident were kept as controls. According
      to technical protocols, toes were injected with a low-viscosity acrylic resin
      (Mercox) through the major digital artery, tissues were corroded in KOH solution
      (8%), and resulting casts processed for SEM observations. Already at low
      magnification, in diabetic toes, we found an impairment of the linear track-like
      disposition of the vessels of plantar side, with signs of vascular disruption and
      obliterations, stopped resin, and leakages. Capillaries under the nail and a lot
      of vascular villi in eponychium and nail borders were damaged, and vascular
      regression phenomena acting on them were clearly visible. Resin leakages and
      impairment of normal vascular architecture were also observed in the root of the
      nail. This preliminary report represents only the first step for further
      investigations regarding morphological three-dimensional appearance of diabetic
      microangiopathy. CC and scanning electron microscopy technique well documented
      these morphological modifications, highlighting on both structural and
      ultrastructural features of diabetic toes microvessels. In conclusion, our
      qualitative data try to better focus on the pathophysiological mechanisms
      involved in diabetic dermopathy and microangiopathy, proposing CC as useful
      method to investigate on them.

PMID- 20687176
TI  - Drug discovery in academic settings.

PMID- 20687175
TI  - Plasma selenium is positively related to performance in neurological tasks
      assessing coordination and motor speed.
AB  - Parkinson's disease (PD) is a degenerative process affecting the striato nigral
      system (SN). Its etiology, although obscure, may involve oxidative damage.
      Selenium, an antioxidant, was shown to protect the SN in animal models. In the
      current study, we investigate the association between plasma selenium
      concentrations and the presence of "soft" neurological signs related to the SN.
      Plasma selenium concentration was assessed in participants of age >=65 years in
      the InCHIANTI study, a population-based cohort study in Tuscany, Italy. PD was
      defined based on standard criteria. "Soft" neurological signs were ascertained by
      physical examination. A total of 1,012 participants were included. No association
      was found between the presence of PD and plasma selenium. There was, however, a
      strong association between plasma selenium and timed performance-based
      assessments. Lower levels of selenium were significantly associated withdecreased
      performance in neurological tests of coordination among older adults. Prospective
      studies are needed to further investigate the effects of selenium on SN
      dysfunction.

PMID- 20687177
TI  - Perestroika in pharma: evolution or revolution in drug development?
AB  - New-drug approvals have remained roughly constant since 1950, while the cost of
      drug development has soared. It seems likely that a more modular approach to drug
      discovery and development will evolve, deriving some features from the not-for
      profit sector. For this to occur, we must address the deficit in human capital
      with expertise in both translational medicine and therapeutics and also in
      regulatory science; utilize regulatory reform to incentivize innovation and the
      expansion of the precompetitive space; and develop an informatics infrastructure
      that permits the global, secure, and compliant sharing of heterogeneous data
      across academic and industry sectors. These developments, likely prompted by the
      perception of crisis rather than opportunity, will require linked initiatives
      among academia, the pharmaceutical industry, the US National Institutes of
      Health, and the US Food and Drug Administration, along with a more adventurous
      role for venture capital. A failure to respond threatens the United States' lead
      in biomedical science and in the development and regulation of novel
      therapeutics.

PMID- 20687178
TI  - Systems pharmacology.
AB  - We examine how physiology and pathophysiology are studied from a systems
      perspective, using high-throughput experiments and computational analysis of
      regulatory networks. We describe the integration of these analyses with
      pharmacology, which leads to new understanding of drug action and enables drug
      discovery for complex diseases. Network studies of drug-target relationships can
      serve as an indication on the general trends in the approved drugs and the drug
      discovery progress. There is a growing number of targeted therapies approved and
      in the pipeline, which meets a new set of problems with efficacy and adverse
      effects. The pitfalls of these mechanistically based drugs are described, along
      with how a systems view of drug action is increasingly important to uncover
      intricate signaling mechanisms that play an important part in drug action,
      resistance mechanisms, and off-target effects. Computational methodologies enable
      the classification of drugs according to their structures and to which proteins
      they bind. Recent studies have combined the structural analyses with analysis of
      regulatory networks to make predictions about the therapeutic effects of drugs
      for complex diseases and possible off-target effects.

PMID- 20687179
TI  - Protein kinase target discovery from genome-wide messenger RNA expression
      profiling.
AB  - Genome-wide messenger RNA profiling provides a snapshot of the global state of
      the cell under different experimental conditions such as diseased versus normal
      cellular states. However, because measurements are in the form of quantitative
      changes in messenger RNA levels, such experimental data does not provide direct
      understanding of the regulatory molecular mechanisms responsible for the observed
      changes. Identifying potential cell signaling regulatory mechanisms responsible
      for changes in gene expression under different experimental conditions or in
      different tissues has been the focus of many computational systems biology
      studies. Most popular approaches include promoter analysis, gene ontology, or
      pathway enrichment analysis, as well as reverse engineering of networks from
      messenger RNA expression data. Here we present a rational approach for
      identifying and ranking protein kinases that are likely responsible for observed
      changes in gene expression. By combining promoter analysis; data from various
      chromatin immunoprecipitation studies such as chromatin immunoprecipitation
      sequencing, chromatin immunoprecipitation coupled with paired-end ditag, and
      chromatin immunoprecipitation-on-chip; protein-protein interactions; and kinase
      protein phosphorylation reactions collected from the literature, we can identify
      and rank candidate protein kinases for knock-down, or other types of functional
      validations, based on genome-wide changes in gene expression. We describe how
      protein kinase candidate identification and ranking can be made robust by cross
      validation with phosphoproteomics data as well as through a literature-based text
      mining approach. In conclusion, data integration can produce robust candidate
      rankings for understanding cell regulation through identification of protein
      kinases responsible for gene expression changes, and thus rapidly advancing drug
      target discovery and unraveling drug mechanisms of action.

PMID- 20687180
TI  - Integration of small-molecule discovery in academic biomedical research.
AB  - Rapid advances in biomedical sciences in recent years have drastically
      accelerated the discovery of the molecular basis of human diseases. The great
      challenge is how to translate the newly acquired knowledge into new medicine for
      disease prevention and treatment. Drug discovery is a long and expensive process,
      and the pharmaceutical industry has not been very successful at it, despite its
      enormous resources and spending on the process. It is increasingly realized that
      academic biomedical research institutions ought to be engaged in early-stage drug
      discovery, especially when it can be coupled to their basic research. To leverage
      the productivity of new-drug development, a substantial acceleration in
      validation of new therapeutic targets is required, which would require small
      molecules that can precisely control target functions in complex biological
      systems in a temporal and dose-dependent manner. In this review, we describe a
      process of integration of small-molecule discovery and chemistry in academic
      biomedical research that will ideally bring together the elements of innovative
      approaches to new molecular targets, existing basic and clinical research,
      screening infrastructure, and synthetic and medicinal chemistry to follow up on
      small-molecule hits. Such integration of multidisciplinary resources and
      expertise will enable academic investigators to discover novel small molecules
      that are expected to facilitate their efforts in both mechanistic research and
      new-drug target validation. More broadly academic drug discovery should
      contribute new entities to therapy for intractable human diseases, especially for
      orphan diseases, and hopefully stimulate and synergize with the commercial
      sector.

PMID- 20687181
TI  - Pursuit of personalized anticancer therapy: leveraging collaboration between
      academia and the biotech/pharmaceutical industry.
AB  - Over the past 2 decades, our increased understanding of tumor biology has
      resulted in the delivery of a new generation of molecularly targeted cancer drugs
      with greater efficacy and less toxicity. This understanding has also provided
      pharmaceutical and academic institutions with a greater appreciation for the
      complexities and challenges associated with discovering and developing
      molecularly targeted drugs. To deal with the complexities of tumor biology and
      the associated technologies needed to develop molecularly targeted drugs, there
      has been increased cooperation and collaboration between academic and
      pharmaceutical-industry researchers in a broader number of aspects of the drug
      discovery and development continuum, including structural biology and
      translational research. This collaborative effort has played a role in
      molecularly targeted drugs such as cetuximab, trastuzumab, imatinib, and new
      promising drug candidates such as OSI-906. Cooperative efforts by industry and
      academia have also provided important insights to optimize the use of such agents
      in the clinic. This review aims to emphasize the need for academic/industrial
      collaborations for success and efficiency through the drug discovery and
      development continuum, and will highlight several examples of collaborations
      between academic and industrial scientists that facilitated the development of
      molecularly targeted antitumor agents into the clinic.

PMID- 20687182
TI  - Drug-based therapies for vascular disease in Marfan syndrome: from mouse models
      to human patients.
AB  - Marfan syndrome is a congenital disorder of the connective tissue with a long
      history of clinical and basic science breakthroughs that have forged our
      understanding of vascular-disease pathogenesis. The biomedical importance of
      Marfan syndrome was recently underscored by the discovery that the underlying
      genetic lesion impairs both tissue integrity and transforming growth factor-beta
      regulation of cell behavior. This discovery has led to the successful
      implementation of the first pharmacological intervention in a connective-tissue
      disorder otherwise incurable by either gene-based or stem cell-based therapeutic
      strategies. More generally, information gathered from the study of Marfan
      syndrome pathogenesis has the potential to improve the clinical management of
      common acquired disorders of connective-tissue degeneration.

PMID- 20687183
TI  - Role of antibodies in developing drugs that target G-protein-coupled receptor
      dimers.
AB  - G-protein-coupled receptors are important molecular targets in drug discovery.
      These receptors play a pivotal role in physiological signaling pathways and are
      targeted by nearly 50% of currently available drugs. Mounting evidence suggests
      that G-protein-coupled receptors form dimers, and various studies have shown that
      dimerization is necessary for receptor maturation, signaling, and trafficking.
      However, the physiological implications of dimerization in vivo have not been
      well explored because detection of GPCR dimers in endogenous systems has been a
      challenging task. One exciting new approach to this challenge is the generation
      of antibodies against specific G-protein-coupled receptor dimers. Such antibodies
      could be used as tools for characterization of heteromer-specific function; as
      reagents for their purification, tissue localization, and regulation in vivo; and
      as probes for mapping their functional domains. In addition, such antibodies
      could serve as alternative ligands for G-protein-coupled receptor heteromers.
      Thus, heteromer-specific antibodies represent novel tools for the exploration and
      manipulation of G-protein-coupled receptor-dimer pharmacology.

PMID- 20687184
TI  - Pharmacokinetic/ pharmacodynamic-driven drug development.
AB  - The drug discovery and development enterprise, traditionally an industrial
      juggernaut, has spanned into the academic arena that is partially motivated by
      the National Institutes of Health Roadmap highlighting translational science and
      medicine. Because drug discovery and development represents a pipeline of basic
      to clinical investigations, it meshes well with the "bench to the bedside" prime
      directive of translational medicine. The renewed interest in drug discovery and
      development in academia provides an opportunity to rethink the hiearchary of
      studies with the hope of improving the staid approaches that have been criticized
      for lacking innovation. One area that has received limited attention concerns the
      use of pharmacokinetic and pharmacodynamic studies in the drug-development
      process. Using anticancer drug development as a focus, this review will address
      past and current deficencies in how pharmacokinetic/pharmacodynamic studies are
      conducted and offer new strategies that might bridge the gap between preclinical
      and clinical trials.

PMID- 20687185
TI  - That I won't translate! Experiences of a family medical interpreter in a
      multicultural environment.
AB  - Family members used as patients' interpreters are a common occurrence in the
      medical environments of multicultural societies. It is recognized that the use of
      the family-member interpreter may have some benefits. However, studies show that
      this option also has substantial disadvantages and therefore suggest that the use
      of professional medical interpreters is the preferable option for effective
      quality care. The purpose of the current study is to present the narrative of a
      family-member interpreter in Israel, a diverse immigrant society. While numerous
      studies have been done on the challenges in the doctor-interpreter-patient
      medical encounter, these studies tend to focus on the experiences of the
      physicians or the patients, and the perspective of the interpreter is often
      sidelined. After discussing the various interpreting options, we suggest that the
      perspective of the family-member interpreter strengthens assertions that
      professional interpretation is the best option for multilingual medical
      environments.

PMID- 20687186
TI  - Joseph's wishes: ethical decision-making in Duchenne muscular dystrophy.
AB  - The death of a child is an uncommon occurrence and can be difficult for families
      to accept. Attempts by the healthcare team to discuss end-of-life issues can be
      so upsetting to families that they refuse to participate in the discussion. Even
      with diseases where an early death can be anticipated, such as Duchenne muscular
      dystrophy, the family is often reluctant to discuss end-of-life issues when the
      patient is relatively healthy, preferring to focus on the current health issues.
      In this article we discuss what happens when there are disagreements between the
      patient and family and the needs of both must be taken into consideration.

PMID- 20687187
TI  - Mammographic screening for breast cancer: 2010.
AB  - Recently, the US Preventive Services Task Force (USPSTF) guidelines concerning
      analog screening mammography were revised. Despite the breast cancer death rate
      falling by 30% since 1990 and mammography receiving the lion's share of credit
      for the decrease, the USPSTF no longer advises routine screening mammography for
      women aged 40-49. Biennial screening is advised for those aged 50-74. The USPSTF
      did not make a recommendation regarding screening those aged > or = 75. The
      recommendations do not cover digital mammography. It is necessary for primary
      care providers to understand the data so they can assist patients making
      decisions about breast cancer screening.

PMID- 20687188
TI  - Synchrotron-based micro-CT imaging of the human lung acinus.
AB  - Structural data about the human lung fine structure are mainly based on
      stereological methods applied to serial sections. As these methods utilize 2D
      images, which are often not contiguous, they suffer from inaccuracies which are
      overcome by analysis of 3D micro-CT images of the never-sectioned specimen. The
      purpose of our study was to generate a complete data set of the intact three
      dimensional architecture of the human acinus using high-resolution synchrotron
      based micro-CT (synMCT). A human lung was inflation-fixed by formaldehyde
      ventilation and then scanned in a 64-slice CT over its apex to base extent. Lung
      samples (8-mm diameter, 10-mm height, N = 12) were punched out, stained with
      osmium tetroxide, and scanned using synMCT at (4 MUm)(3) voxel size. The lung
      functional unit (acinus, N = 8) was segmented from the 3D tomographic image using
      an automated tree-analysis software program. Morphometric data of the lung were
      analyzed by ANOVA. Intra-acinar airways branching occurred over 11 generations.
      The mean acinar volume was 131.3 +/- 29.2 mm(3) (range, 92.5-171.3 mm(3)) and the
      mean acinar surface was calculated with 1012 +/- 26 cm(2). The airway internal
      diameter (starting from the bronchiolus terminalis) decreases distally from 0.66
      +/- 0.04 mm to 0.34 +/- 0.06 mm (P < 0.001) and remains constant after the
      seventh generation (P < 0.5). The length of each generation ranges between 0.52
      and 0.93 mm and did not show significant differences between the second and
      eleventh generation. The branching angle between daughter branches varies between
      113-degree and 134-degree without significant differences between the generations
      (P < 0.3). This study demonstrates the feasibility of quantitating the 3D
      structure of the human acinus at the spatial resolution readily achievable using
      synMCT.

PMID- 20687189
TI  - Pet findings in reversible improvement of olfactory dysfunction after STN
      stimulation in a Parkinson's disease patient.

PMID- 20687190
TI  - Exercise dependence induced by pramipexole in Parkinson's Disease-a case report.

PMID- 20687191
TI  - DYT6 dystonia: mutation screening, phenotype, and response to deep brain
      stimulation.
AB  - Mutations in THAP1, a gene encoding a nuclear pro-apoptotic protein, have been
      associated with DYT6 dystonia. First reports on the phenotype of DYT6 dystonia
      show an early onset dystonia with predominant cranio-cervical and laryngeal
      involvement. Here we assessed the frequency and phenotype of THAP1 mutation
      carriers in a large Dutch cohort of adult-onset (>=26 years) dystonia (n = 388)
      and early-onset dystonia (n = 67) patients. We describe the phenotype of DYT6
      dystonia patients and their response on GPi DBS. Overall, 3 nonsynonymous
      heterozygous mutations were detected in the early-onset group (4.5%). Two DYT6
      families were identified, showing a heterozygous phenotype. All patients had
      segmental or generalized dystonia, often associated with profound oromandibular
      and laryngeal involvement. No nonsynonymous mutations were found in patients with
      adult-onset focal dystonia. Rare synonymous variants were identified in conserved
      regions of THAP1, two in the adult-onset cervical dystonia group and one in the
      control group. Four DYT6 dystonia patients were treated with GPi DBS with
      moderate to good response on motor function but marginal benefit on speech.

PMID- 20687193
TI  - Clinical neuroimaging and electrophysiological assessment of three DYT6 dystonia
      families.
AB  - The purpose of the study was to delineate clinical and electrophysiological
      characteristics as well as laryngoscopical and transcranial ultrasound (TCS)
      findings in THAP1 mutation carriers (MutC). According to recent genetic studies,
      DYT6 (THAP1) gene mutations are an important cause of primary early-onset
      dystonia. In contrast to DYT1 mutations, THAP1 mutations are associated with
      primary early-onset segmental or generalised dystonia frequently involving the
      craniocervical region and the larynx. Blood samples from twelve individuals of
      three German families with DYT6 positive index cases were obtained to test for
      THAP1 mutations. Eight THAP1 MutC were identified. Of these, six (three
      symptomatic and three asymptomatic) THAP1 MutC could be clinically evaluated.
      Laryngoscopy was performed to evaluate laryngeal dysfunction in patients.
      Brainstem echogenicity was investigated in all MutC using TCS. Two of the
      patients had undergone bilateral pallidal DBS. In all three symptomatic MutC,
      early-onset laryngeal dystonia was a prominent feature. Laryngeal assessment
      demonstrated adductor-type dystonia in all of them. On clinical examination, the
      three asymptomatic MutC also showed subtle signs of focal or segmental dystonia.
      TCS revealed increased substantia nigra (SN) hyperechogenicity in all MutC.
      Intraoperative microelectrode recordings under general anesthesia in two of the
      patients showed no difference between THAP1 and previously operated DYT1 MutC.
      The presence of spasmodic dysphonia in patients with young-onset segmental or
      generalised dystonia is a hallmark of DYT6 dystonia. SN hyperechogenicity on TCS
      may represent an endophenotype in these patients. Pallidal DBS in two patients
      was unsatisfactory.

PMID- 20687192
TI  - Colonic transcriptional profiling in resistance and susceptibility to
      trichuriasis: phenotyping a chronic colitis and lessons for iatrogenic
      helminthosis.
AB  - BACKGROUND: Helminth therapy is advocated to restore and maintain control of
      inflammatory responses, particularly chronic colitis. However, helminths can
      induce chronic colitis in susceptible individuals. Susceptibility has an
      immunogenetic basis: defining this is essential if nematode therapy is to be
      successfully and safely targeted in inflammatory bowel disease (IBD). To validate
      a preclinical mouse model we phenotyped the response to Trichuris muris in mice.
      We determined colonic transcriptional activity in naive and infected mice and
      linked differential gene expression to mechanistic pathways. METHODS: T. muris
      infected resistant (BALB/c) and susceptible (AKR) mice were studied to a chronic
      colitic timepoint (day 35). Colonic genome-wide expression was performed by
      microarray. Significant transcriptional changes were analyzed by cluster and gene
      ontology filtering and KEGG pathway mapping. RESULTS: Day 35 infected AKR
      displayed chronic diarrhea, weight loss, and transmural colonic inflammation;
      BALB/c remained asymptomatic, cleared the infection, and demonstrated normal
      histology. Compared to BALB/c mice, infected AKR upregulated gene expression
      clusters were overrepresented by immune response, chemotaxis, and apoptosis
      pathways. Cellular/tissue homeostasis and tight junction pathways dominated
      downregulated AKR expression clusters. Infected AKR T-helper cell
      development/polarization markers demonstrated predominant T(H) 1/T(H) 17
      transcriptional activity. Colitic AKR data mirrored established murine models and
      human colitis. CONCLUSIONS: T. muris infection in the mouse shows striking
      phenotypic and transcriptional similarities to widely used models of IBD and
      human IBD. This preclinical mouse model presents a platform to examine biological
      commonalities among chronic colitides. However, these data urge caution in
      untargeted therapeutic helminth use until risk/benefit in susceptible individuals
      is more fully understood.

PMID- 20687194
TI  - Combined therapy versus usual care for the treatment of depression in oncologic
      patients: a randomized controlled trial.
AB  - OBJECTIVE: To compare narrative therapy (NT) plus escitalopram versus
      escitalopram plus usual care on quality of life and depressive symptomatology of
      depressed patients with oncologic disease. METHODS: A total of 72 subjects (mean
      age 54.6 years), predominantly female with non-metastatic breast, lung and colon
      cancer and depressive disorder (DSM-IV-TR) were randomized to receive treatment
      with NT plus escitalopram (n=39) or escitalopram (10-20 mg QD) plus usual care
      (n=33). Main endpoints were improvement in dimensions of quality of life measured
      by the European Organization for Research and Treatment of Cancer Quality of Life
      Questionnaire C-30 and reduction of depressive symptoms using the Hospital
      Anxiety and Depression Scale at weeks 12 and 24. RESULTS: The combined therapy
      group showed significantly greater improvement in all the functioning dimensions
      (p<0.01), pain scale (p=0.02), global health (p=0.02), and global quality of life
      (p=0.007) at weeks 12 and 24. There were no statistically significant differences
      in depressive symptomatology between the groups. From week 12 to week 24 study
      retention was higher in the combined treatment group (p=0.01). CONCLUSIONS: Brief
      NT in combination with escitalopram was superior to usual care and escitalopram
      in improving functioning dimensions of quality life.

PMID- 20687195
TI  - Identification of patient-reported distress by clinical nurse specialists in
      routine oncology practice: a multicentre UK study.
AB  - BACKGROUND: There is uncertainty regarding how well clinical nurse specialists
      are able to identify distress in cancer settings. METHODS: We examined
      recognition of patient-reported distress by nurse specialists across three sites
      in the East Midlands (UK). Clinicians were asked to report on their clinical
      opinion regarding the presence of distress or any mental health complication
      after routine assessment of 401 mixed cancer patients. Patient-reported distress
      was defined by the distress thermometer at a cut-off of 4 or higher. RESULTS: We
      found that the prevalence of patient-reported distress was 45.4%. The rates for
      mild, moderate and severe distress were: 23.4, 13.7 and 8.2, respectively. When
      looking for distress (or any mental health complication) nurse practitioners had
      a detection sensitivity of 50.5% and specificity 80.0%. Cohen's kappa suggested
      fair agreement between staff and patients. Examining predictors of distress,
      clinicians were better able to recognise higher severities of distress (adjusted
      R(2) =0.87 P=0.001). There was lower sensitivity in palliative stages but no
      differences according to the type of cancer. There was also higher sensitivity
      but lower specificity in those clinicians with high self-rated confidence.
      CONCLUSIONS: Nurses working in cancer settings have difficulty identifying
      distress using their routine clinical judgement and tend to make more false
      negative than false-positive errors. Evidence-based strategies that improve
      detection of mild and moderate distress are required in routine cancer care.

PMID- 20687196
TI  - Can health beliefs help in explaining attendance to follow-up care? The Swiss
      childhood cancer survivor study.
AB  - OBJECTIVE: Improved treatment has increased the survival of childhood cancer
      patients in recent decades, but follow-up care is recommended to detect and treat
      late effects. We investigated relationships between health beliefs and follow-up
      attendance in adult childhood cancer survivors. METHODS: Childhood cancer
      survivors aged younger than 16 years when diagnosed between 1976 and 2003, who
      had survived for more than 5 years and were currently aged 20+ years, received a
      postal questionnaire. We asked survivors whether they attended follow-up in the
      past year. Concepts from the Health Belief Model (perceived susceptibility and
      severity of future late effects, potential benefits and barriers to follow-up,
      general health value and cues to action) were assessed. Medical information was
      extracted from the Swiss Childhood Cancer Registry. RESULTS: Of 1075 survivors
      (response rate 72.3%), 250 (23.3%) still attended regular follow-up care. In
      unadjusted analyses, all health belief concepts were significantly associated
      with follow-up (p<0.05). Adjusting for other health beliefs, demographic, and
      medical variables, only barriers (OR=0.59; 95%CI: 0.43-0.82) remained
      significant. Younger survivors, those with lower educational background,
      diagnosed at an older age, treated with chemotherapy, radiotherapy, or bone
      marrow transplantation and with a relapse were more likely to attend follow-up
      care. CONCLUSIONS: Our study showed that more survivors at high risk of cancer-
      and treatment-related late effects attend follow-up care in Switzerland. Patient
      perceived barriers hinder attendance even after accounting for medical variables.
      Information about the potential effectiveness and value of follow-up needs to be
      available to increase the attendance among childhood cancer survivors.

PMID- 20687197
TI  - Analyses of second-generation 'legal highs' in the UK: initial findings.
AB  - In the UK, mephedrone and other so-called 'legal high' derivatives have recently
      been classified as Class B, Schedule I under the Misuse of Drugs Act 1971. Since
      then, alternative products have been advertised on a number of websites. In order
      to obtain an immediate snapshot of the situation, 24 products were purchased
      online from 18 UK-based websites over a period of 6 weeks following the ban in
      April 2010. Qualitative analyses were carried out by gas chromatography ion trap
      mass spectrometry using electron- and chemical ionization modes, nuclear magnetic
      resonance spectroscopy, and comparison with reference standards. Overall, the
      purchased products consisted of single cathinones or cathinone mixtures including
      mephedrone, butylone, 4-methyl-N-ethylcathinone, flephedrone (4
      fluoromethcathinone) and MDPV (3,4-methylenedioxypyrovalerone), respectively.
      Benzocaine, caffeine, lidocaine, and procaine were also detected. The emphasis
      was placed on 'Energy 1' (NRG-1), a product advertised as a legal replacement for
      mephedrone-type derivatives usually claiming to contain naphyrone
      (naphthylpyrovalerone, O-2482). It was found that 70% of NRG-1 and NRG-2 products
      appeared to contain a mixture of cathinones banned in April 2010 and rebranded as
      'new' legal highs, rather than legal chemicals such as naphyrone as claimed by
      the retailers. Only one out of 13 NRG-1 samples appeared to show analytical data
      consistent with naphyrone. These findings also suggest that both consumers and
      online sellers (unlike manufacturers and wholesalers) are, most likely
      unknowingly, confronted with the risk of criminalization and potential harm.

PMID- 20687198
TI  - Simple tools for teaching gross anatomy to undergraduate medical students.

PMID- 20687199
TI  - Cytogenetic abnormalities in reactive lymphoid hyperplasia: byproducts of the
      germinal centre reaction or indicators of lymphoma?
AB  - Non-random karyotypic abnormalities associated with non-Hodgkin lymphomas (NHLs)
      have been described in cases of reactive lymphoid hyperplasia (RLH). However, the
      frequency and types of cytogenetic aberrations detected and their clinical
      relevance are unknown. To address these questions, we undertook a retrospective
      analysis of a large series of RLH diagnosed at our institute over 8 years.
      Cytogenetic abnormalities were identified in 20 of 116 (17%) cases with
      informative karyotypes, comprising 14 (70%) structural and 11 (55%) numerical
      changes. Clonal (n  =  14, 70%) and non-clonal (n  =  6, 30%) abnormalities were
      observed. Aberrations of chromosome 14 were the most frequent (n = 8, 42%, 7
      represented IgH translocations), followed by chromosome 3 (n  =  4, 3 represented
      BCL6 translocations), and chromosome 12 (n = 4). Abnormal karyotypes were most
      often associated with florid follicular hyperplasia. Isolated lymphoid organ
      (lymph node, tonsil or spleen) enlargement (12/20, 60%) was more common, no
      specific etiology was identified in 10/20 (50%) cases and only 1 of 18 patients
      with clinical follow-up (range 2-107 months, median 60 months) developed
      lymphoma. In our experience, cytogenetic abnormalities involving loci associated
      with B-cell NHL are not infrequently detected in RLH. Their occurrence portends
      low risk for lymphomagenesis, however longer follow-up is prudent to further
      evaluate the natural history of such cases.

PMID- 20687200
TI  - Automated Sholl analysis of digitized neuronal morphology at multiple scales:
      Whole cell Sholl analysis versus Sholl analysis of arbor subregions.
AB  - The morphology of dendrites and the axon determines how a neuron processes and
      transmits information. Neurite morphology is frequently analyzed by Sholl
      analysis or by counting the total number of neurites and branch tips. However,
      the time and resources required to perform such analysis by hand is prohibitive
      for the processing of large data sets and introduces problems with data auditing
      and reproducibility. Furthermore, analyses performed by hand or using course
      grained morphometric data extraction tools can obscure subtle differences in data
      sets because they do not store the data in a form that facilitates the
      application of multiple analytical tools. To address these shortcomings, we have
      developed a program (titled "Bonfire") to facilitate digitization of neurite
      morphology and subsequent Sholl analysis. Our program builds upon other available
      open-source morphological analysis tools by performing Sholl analysis on
      subregions of the neuritic arbor, enabling the detection of local level changes
      in dendrite and axon branching behavior. To validate this new tool, we applied
      Bonfire analysis to images of hippocampal neurons treated with 25 ng/ml brain
      derived neurotrophic factor (BDNF) and untreated control neurons. Consistent with
      prior findings, conventional Sholl analysis revealed that global exposure to BDNF
      increases the number of neuritic intersections proximal to the soma. Bonfire
      analysis additionally uncovers that BDNF treatment affects both root processes
      and terminal processes with no effect on intermediate neurites. Taken together,
      our data suggest that global exposure of hippocampal neurons to BDNF results in a
      reorganization of neuritic segments within their arbors, but not necessarily a
      change in their number or length. These findings were only made possible by the
      neurite-specific Sholl data returned by Bonfire analysis.

PMID- 20687201
TI  - Variables in the quantification of CD4 in normals and hairy cell leukemia
      patients.
AB  - BACKGROUND: Quantitative flow cytometry (QFCM) is being applied in the clinical
      flow cytometry laboratory. Quantitative normal T-cell CD4 expression represents a
      biologic standard and quality control agent. However, low levels of CD4
      expression were detected in normal T-cells in Hairy Cell Leukemia (HCL) samples.
      METHODS: The QuantiBrite System(r) was used to determine the level of CD4
      expression (mean antibody bound per cell, ABC) in fresh and shipped HCL blood and
      fresh normal donor blood (NDB). The effects of shipping, lysing reagent, cell
      preparation method, and antibody lot were evaluated. RESULTS: Shipped HCL
      specimens (n = 69) had a significantly lower mean CD4 ABC of 38,788 (CV = 9.1%)
      compared to fresh specimens (n = 105) CD4 value of 40,330 (CV = 8.4%) (P < 0.05).
      In NDB, significant differences were seen for fresh versus shipped specimens
      using the stain/lyse method but not for lyse/stain method. Consistent differences
      in CD4 ABC based upon antibody lot were observed in fresh HCL and NDB samples.
      Stain/lyse and lyse/stain methods using NH(4) Cl lyse were compared in NDB using
      identical samples and antibodies. The NDB CD4 ABC values obtained with the lyse
      (NH(4) Cl)/stain method (45,562, 3.7% CV) were lower than those obtained with the
      stain/lyse (NH(4) Cl) method (49,955, 3.3% CV) with P < 0.001. CONCLUSIONS: CD4
      expression in HCL patient samples is not inherently different from that observed
      in NDB and therefore may serve as a biological control in clinical QFCM.
      Technical variables impact significantly on QFCM of CD4.

PMID- 20687202
TI  - Evaluation of degranulation and cytokine production in natural killer cells from
      spondyloarthritis patients at single-cell level.
AB  - BACKGROUND: A pathogenetic role of natural killer (NK) cells has been
      hypothesized in spondyloarthritides (SpA), but still conflicting data exist. Aim
      of this study was to investigate, in a cohort of SpA patients, the peripheral
      blood NK cell number, the cytokine production (IFNgamma and TNFalpha), and the
      cytotoxic activity on target cell stimulation. Moreover, we aimed to evaluate the
      expression of KIR3DL1, an inhibitory receptor binding HLA class I alleles,
      including HLA-B27 strongly associated with SpA, between different NK cell
      subsets. METHODS: We enrolled 21 SpA patients and 21 healthy controls. Multicolor
      flow cytometry was used to analyze the cytokine levels triggered by activating
      receptors, the degranulation as CD107a surface expression on target cell
      stimulation, the number and KIR3DL1 expression on peripheral blood NK cells.
      RESULTS: When stimulated with P815 cells preincubated with antibodies against
      activating receptors, NK cells produced IFNgamma to a lesser extent respect to
      healthy controls (P = 0.0012). No differences were found in TNFalpha production
      and NK cell degranulation in patients and controls. We observed a higher
      frequency of KIR3DL1-positive NK cells from SpA patients than in controls (P =
      0.02). Similar results were obtained in NK cell subsets. CONCLUSIONS: In our SpA
      patients, we observed a reduced IFNgamma production, which may be explained by
      the elevated frequency of KIR3DL1-expressing NK cells, while the other parameters
      were similar to those of healthy controls. These results may support the role of
      NK cells in the pathogenesis of SpA, although more data are needed to
      substantiate these observations.

PMID- 20687203
TI  - Flow cytometric analysis of peripheral blood dendritic cells in patients with
      severe sepsis.
AB  - BACKGROUND: Dendritic cells (DC) play a key role in cell-mediated immunity. We
      aimed to analyse the number and function of peripheral blood (PB) myeloid and
      plasmacytoid DC (mDC/pDC) in patients with severe sepsis. METHODS: Twenty-six
      septic patients, 20 surgical patients (abdominal aortic aneurysm) and 20 healthy
      controls were enrolled in this prospective study. RESULTS: At day 1 (enrollment
      in the study), septic patients showed in comparison with healthy controls,
      decreased mDC (P < 0.001) and increased pDC (P = 0.03), resulting in a reduction
      of the mDC/pDC ratio (P < 0.001). Surgery induced a decrease in both mDCs and
      pDCs level, without modification of mDC/pDC ratio. Septic patients included 15
      survivors and 11 nonsurvivors. At day 1 no significant difference was found in
      mDC between the two groups, while pDCs were significantly higher in nonsurvivors
      (P = 0.03). At the outcome, mDC were selectively increased with respect to day 1
      in survivors (P = 0.001), while no significant differences were observed as far
      as pDC count is concerned in both groups. Sorted DC from septic patients showed
      in comparison with healthy controls, reduced levels of HLA DR (P < 0.001), CD11c
      (P < 0.001), CD83 (P = 0.006) and of costimulatory molecule CD86 (P = 0.003); an
      up-regulation of chemokine receptor CXCR4 (P = 0.031) and increased apoptosis (P
      < 0.001). CONCLUSIONS: Sepsis has a profound effect on PB DC compartment. These
      alterations appear to be sepsis-specific. Increased apoptosis and alteration of
      migration and trafficking mechanism may be involved in DC compartment
      modification. DC alterations could contribute to sepsis-mediated immunoparalysis.

PMID- 20687204
TI  - Etiologies of spontaneous pneumomediastinum in children in middle Taiwan.
AB  - SUMMARY INTRODUCTION: Spontaneous pneumomediastinum (SPM), while rare, is
      probably underestimated in children. Treatment targets on the underlying disease
      and trigger factors. The study aimed in analysis different etiology in different
      age groups. PATIENTS AND METHODS: Total 37 children with SPM were analyzed from
      two medical centers in middle Taiwan from 1994 to 2007. RESULTS: Incidence of SPM
      in children was 1:11,726 patients at Department of Pediatric Emergency in middle
      Taiwan. Bimodal peak in incidence occurred in those under 7 and in those aged 15
      18 years old. The Characteristic symptoms were dyspnea (64.9%), followed by chest
      pain (62.2%) and neck pain (40.5%); common specific physical signs were
      subcutaneous emphysema (SCE) (67.6%) and Hammer's sign (13.5%). Trigger factors
      were infection (43.2%), asthma (21.0%), esophageal rupture (5.4%), foreign body
      aspiration (2.7%), and diabetic ketoacidosis (2.7%). Idiopathic SPM accounted for
      35.1% of patients with mean age 14.1 years. In age distribution, preschoolers (<7
      years old) got SPM mostly due to lower respiratory tract infection. In
      adolescents, the most common etiologies were asthma and upper respiratory tract
      infection. Mean hospitalization was 6.4 days. Although 17 (46.0%) patients needed
      intensive care, nearly all had complete resolution in chest radiography before
      discharge. CONCLUSION: Clinician should keep alert to incidence of SPM from these
      symptoms. Etiologies varied with age and treatment must target on factors and
      underlying disease.

PMID- 20687205
TI  - Successful diagnosis and treatment of congenital tracheal web using a fiberoptic
      bronchoscope.
AB  - SUMMARY: Congenital tracheal web is a very rare abnormality that often manifests
      as wheezing, dyspnea, and respiratory failure. Misdiagnosis is common. Here we
      describe the case of a 47-day-old female infant who presented after severe,
      extended coughing. The diagnosis of congenital tracheal web was made following
      coronal computer tomography (CT) reconstruction and bronchoscopy. The
      bronchoscope was used to facilitate tracheal expansion. This is the youngest case
      reported to date to highlight the diagnosis and treatment of a 47 days infant
      with congenital tracheal web. An infant with tracheal web, a very rare congenital
      anomaly can be clearly diagnosed by coronal CT reconstruction combined with
      bronchoscopy. If diagnosed early, the bronchoscope may be used to facilitate
      tracheal expansion.

PMID- 20687206
TI  - A phase I trial of deep brain stimulation of memory circuits in Alzheimer's
      disease.
AB  - OBJECTIVE: Alzheimer disease (AD) is characterized by functional impairment in
      the neural elements and circuits underlying cognitive and memory functions. We
      hypothesized that fornix/hypothalamus deep brain stimulation (DBS) could modulate
      neurophysiological activity in these pathological circuits and possibly produce
      clinical benefits. METHODS: We conducted a phase I trial in 6 patients with mild
      AD receiving ongoing medication treatment. Patients received continuous
      stimulation for 12 months. Three main lines of investigation were pursued
      including: (1) mapping the brain areas whose physiological function was modulated
      by stimulation using standardized low-resolution electromagnetic tomography, (2)
      assessing whether DBS could correct the regional alterations in cerebral glucose
      metabolism in AD using positron emission tomography (PET), and 3) measuring the
      effects of DBS on cognitive function over time using clinical scales and
      instruments. RESULTS: DBS drove neural activity in the memory circuit, including
      the entorhinal, and hippocampal areas and activated the brain's default mode
      network. PET scans showed an early and striking reversal of the impaired glucose
      utilization in the temporal and parietal lobes that was maintained after 12
      months of continuous stimulation. Evaluation of the Alzheimer's Disease
      Assessment Scale cognitive subscale and the Mini Mental State Examination
      suggested possible improvements and/or slowing in the rate of cognitive decline
      at 6 and 12 months in some patients. There were no serious adverse events.
      INTERPRETATION: There is an urgent need for novel therapeutic approaches for AD.
      Modulating pathological brain activity in this illness with DBS merits further
      investigation.

PMID- 20687207
TI  - Glut1 deficiency: inheritance pattern determined by haploinsufficiency.
AB  - Two families manifesting Glut1 deficiency syndrome (DS) as an autosomal recessive
      trait are described. In 1 family, a severely affected boy inherited a mutated
      allele from his asymptomatic heterozygous mother. A de novo mutation developed in
      the paternal allele, producing compound heterozygosity. In another family, 2
      mildly affected sisters inherited mutations from their asymptomatic heterozygous
      consanguineous parents. Red blood cell glucose uptake residual activity, a
      surrogate of haploinsufficiency, correlated with the clinical severity. These
      cases demonstrate that Glut1 DS may present as an autosomal recessive trait. The
      clinical pattern of inheritance is determined by the relative pathogenicity of
      the mutation and the resulting degree of haploinsufficiency.

PMID- 20687208
TI  - Meningeal T cells associate with diffuse axonal loss in multiple sclerosis spinal
      cords.
AB  - OBJECTIVE: A link between diffuse axonal loss and diffuse inflammation has been
      established in the brain of patients with progressive multiple sclerosis (MS). In
      the present paper, we sought to determine whether such a link could be similarly
      demonstrated in the spinal cord of patients with progressive MS. METHODS: A
      neuropathological quantitative assessment of inflammation and axonal loss was
      performed in the cervical spinal cord of 18 patients with progressive MS and 5
      control subjects. RESULTS: As previously reported, we found a mean 25% decrease
      of axonal density in the normal-appearing white matter (NAWM) of MS versus
      control spinal cords. T-cell perivascular infiltrates were rare, but a robust
      diffuse inflammation was observed in both the normal-appearing parenchyma and the
      meninges. The extent of diffuse axonal loss in the NAWM correlated with both the
      density of major histocompatibility complex (MHC) class II(+) microglia in the
      NAWM and, surprisingly, the density of CD3(+) T cells in the meninges.
      Interestingly, close interactions between T cells and MHC class II(+) macrophages
      were observed in the meninges of spinal cords from MS patients. INTERPRETATION:
      Recent studies assigned a major role to meningeal B-cell follicles in the
      pathophysiology of secondary progressive MS. The present work also emphasizes the
      link between meningeal inflammation and parenchymal lesions and points to a
      specific role exerted by both meningeal T cells and activated microglia in
      diffuse axonal loss in the spinal cord.

PMID- 20687209
TI  - 18F-flutemetamol amyloid imaging in Alzheimer disease and mild cognitive
      impairment: a phase 2 trial.
AB  - OBJECTIVE: The most widely studied positron emission tomography ligand for in
      vivo beta-amyloid imaging is (11)C-Pittsburgh compound B ((11)C-PIB). Its
      availability, however, is limited by the need for an on-site cyclotron.
      Validation of the (18)F-labeled PIB derivative (18)F-flutemetamol could
      significantly enhance access to this novel technology. METHODS: Twenty-seven
      patients with early-stage clinically probable Alzheimer disease (AD), 20 with
      amnestic mild cognitive impairment (MCI), and 15 cognitively intact healthy
      volunteers (HVs) above and 10 HVs below 55 years of age participated. The primary
      endpoint was the efficacy of blinded visual assessments of (18)F-flutemetamol
      scans in assigning subjects to a raised versus normal uptake category, with
      clinical diagnosis as the standard of truth (SOT). As secondary objectives, we
      determined the correlation between the regional standardized uptake value ratios
      (SUVRs) for (18)F-flutemetamol and its parent molecule (11)C-PIB in 20 of the AD
      subjects and 20 of the MCI patients. We also determined test-retest variability
      of (18)F-flutemetamol SUVRs in 5 of the AD subjects. RESULTS: Blinded visual
      assessments of (18)F-flutemetamol scans assigned 25 of 27 scans from AD subjects
      and 1 of 15 scans from the elderly HVs to the raised category, corresponding to a
      sensitivity of 93.1% and a specificity of 93.3% against the SOT. Correlation
      coefficients between cortical (18)F-flutemetamol SUVRs and (11)C-PIB SUVRs ranged
      from 0.89 to 0.92. Test-retest variabilities of regional SUVRs were 1 to 4%.
      INTERPRETATION: (18)F-Flutemetamol performs similarly to the (11)C-PIB parent
      molecule within the same subjects and provides high test-retest replicability and
      potentially much wider accessibility for clinical and research use.

PMID- 20687210
TI  - A novel in vitro assay of tumor-initiating cells in xenograft prostate tumors.
AB  - BACKGROUND: The field of prostate cancer has been stymied by the difficulty of
      cultivating patient-derived samples in the laboratory. In order to help
      circumvent this challenge, we sought to develop an in vitro assay of human
      prostate cancer initiation employing a prostate-associated mesenchymal feeder
      layer. METHODS: Rat seminal vesicle mesenchyme (rSVM) harvested from male
      neonatal rats was plated in 12-well plates and then irradiated with 30 Gy after
      approximately 75% confluence. Single-cell suspensions of two human non-adherent
      prostate cancer xenograft lines (TRPC and LAPC9) were then plated on irradiated
      rSVM. At 3-4 weeks, three-dimensional solid structures, termed glandoids, were
      harvested and analyzed or transplanted singly into the renal capsule of
      immunodeficient mice. Animals were assessed for tumor formation 8-12 weeks after
      engraftment. Finally, clonality assays were performed to determine whether
      glandoids usually arise from a single cell and are therefore clonal in origin.
      RESULTS: Glandoids form with reliable frequency (1/ approximately 300 plated
      cells), are constituted by relevant cell types (CK8+, CK5-, PSA+) and after
      implantation into immunocompromised mice, give rise to tumors that recapitulate
      original xenograft histology and cell composition; defining a glandoid as a tumor
      initiating unit. In addition, assessment of red fluorescent protein (RFP)-labeled
      glandoids revealed either all red or non-red structures, with few areas of
      fusion, suggesting glandoids are clonal in origin. CONCLUSIONS: The above assay
      describes an adjunct technique to readily cultivate cells from prostate cancer
      xenografts in vitro and as such provides a platform on which tumor-initiating
      cell studies and high-throughput drug discovery may be performed.

PMID- 20687211
TI  - Targeting tumor metabolism with 2-deoxyglucose in patients with castrate
      resistant prostate cancer and advanced malignancies.
AB  - BACKGROUND: A profound difference between cancer and normal tissues is the
      preferential utilization of glycolysis by cancer cells. To translate this
      paradigm in the clinic, we completed a phase I study of 2-deoxyglucose (2DG), and
      assessed 2DG uptake with fluorodeoxyglucose (FDG) positron emission tomography
      (PET) and the autophagy substrate p62 as a marker of 2DG resistance. METHODS:
      Patients received 2DG orally on days 1-14 of a 21-day cycle in cohorts of three
      in a dose-escalating manner. Correlative assessments included PET scans at
      baseline and day 2 and p62 protein in peripheral blood mononuclear cells as a
      potential marker of 2DG resistance. RESULTS: The dose of 45 mg/kg was defined as
      the recommended phase II dose, secondary to dose-limiting toxicity of grade 3
      asymptomatic QTc prolongation at a dose of 60 mg/kg. PK evaluation of 2DG
      revealed linear pharmacokinetics with C(max) 45 microg/ml (277 microM), 73.7
      microg/ml (449 microM), and 122 microg/ml (744 microM) in dose levels 30, 45, and
      60 mg/kg, respectively. Five of eight patients assessed with FDG-PET scanning
      demonstrated decreased FDG uptake by day 2 of therapy, suggesting competition of
      2DG with FDG. Five of six patients assessed for p62 had a decrease in p62 at 24
      hr. CONCLUSIONS: These data support the safety of 2DG, defined 2DG PK,
      demonstrated the effect of 2DG on FDG-PET imaging, and demonstrated the
      feasibility of assessment of p62 as an autophagic resistance marker. These data
      support future studies of 2DG alone or in combination with approaches to abrogate
      autophagy.

PMID- 20687212
TI  - Serum prostate-specific antigen levels reflect the androgen milieu in patients
      with localized prostate cancer receiving androgen deprivation therapy: Tumor
      malignant potential and androgen milieu.
AB  - BACKGROUND: Although androgen deprivation therapy (ADT) has a marked impact on
      the androgen milieu in vivo and outcomes of prostate cancer (PCa), it remains
      unclear which parameters reflect the androgen milieu during ADT or whether the
      milieu is associated with PCa aggressiveness. METHODS: Seventy-two patients with
      localized PCa were prospectively studied based on their blood samples before and
      after ADT for 6 months. Serum androgens and related values were measured.
      RESULTS: Before ADT, there was no correlation between the serum prostate-specific
      antigen (PSA) and androgen levels. After ADT, the serum PSA levels were
      correlated with each level of serum testosterone, dihydrotestosterone,
      androstenedione, dehydroepiandrosterone-sulfate (DHEA-S), and 3alpha-diol G (P <
      0.010 in all). Before ADT, patients with Gleason score of > or = 8 were likely to
      have lower serum testosterone levels than those with Gleason score of < or = 6 (P
      = 0.058). After ADT, conversely, the testosterone levels in patients with Gleason
      score of > or = 8 appeared to be higher than in those with Gleason score of < or
      = 6 (P = 0.060). The serum DHEA-S level was correlated with Gleason score before
      and after ADT (P = 0.050 and P = 0.040, respectively). CONCLUSIONS: The serum PSA
      levels well reflect the androgen milieu in localized PCa patients receiving ADT,
      which can be explained by the Saturation Model and disease control. The androgen
      milieu in men with high Gleason score PCa is probably less affected by
      conventional ADT than that in men with low score cancer, which was suggested to
      be associated with adrenal androgen levels.

PMID- 20687213
TI  - A transcriptional signature associated with the onset of benign prostate
      hyperplasia in a canine model.
AB  - BACKGROUND: Benign prostatic hyperplasia (BPH) represents the most frequent
      proliferative abnormality of the human prostate. In spite of the well
      characterized architectural development of BPH, little is known about the
      cellular and molecular events that contribute to it. METHODS: We have developed
      an animal model to evaluate the follow-up of hormone-induced BPH and the analysis
      of the gene expression associated with BPH. Immunohistochemistry on human patient
      samples validated the BPH-related molecular alterations. RESULTS: Canine specific
      Affymetrix microarray analysis performed on sequential biopsies obtained from a
      beagle dog dynamic model characterized a number of genes altered during the onset
      of BPH. In addition to the genes involved in calcification, matrix remodeling,
      detoxification, cell movement, and mucosa protection (MGP, MMP2, TIMP2, ITIH3,
      GST, MT2A, SULT1A1, FKBP1B, MUC1, STRBP, TFF3), the up-regulation of TGFB3 and
      CLU indicated a complete adjustment of the transdifferentiation, senescence and
      apoptosis programs. The up-regulation of Clusterin was validated by RT-qPCR and
      immunohistochemistry, both in the dog dynamic model and in human samples, further
      confirming the suitability of the animal model for the study of the molecular
      alterations associated with BPH. CONCLUSIONS: Transcriptome analysis performed on
      a dynamic animal model that accurately mimicked the human clinic, allowed us to
      characterize a gene expression pattern associated with the onset of BPH.

PMID- 20687214
TI  - High-resolution animal PET imaging of prostate cancer xenografts with three
      different 64Cu-labeled antibodies against native cell-adherent PSMA.
AB  - BACKGROUND: The prostate specific membrane antigen (PSMA) is expressed by
      virtually all prostate cancers and represents an ideal target for diagnostic and
      therapeutic strategies. This article compares the in vivo behavior and tumor
      uptake of three different radiolabeled anti-PSMA monoclonal antibodies (mAbs) and
      corresponding F(ab)(2) and Fab fragments thereof. METHODS: The mAbs 3/A12, 3/F11,
      and 3/E7 and fragments of 3/A12 were conjugated with the chelating agent DOTA and
      radiolabeled with 64Cu. For the microPET imaging studies, SCID mice bearing PSMA
      positive C4-2 and PSMA-negative DU 145 prostate cancer xenografts were used. Each
      animal received 20-30 microg radiolabeled mAb or fragment corresponding to an
      activity of 8-14 MBq. Imaging was performed 3, 24, and 48 hr post-injection.
      After the last scan, mice were sacrificed and tracer in vivo biodistribution was
      measured by gamma-counting. RESULTS: Static microPET images of mice with PSMA
      positive tumors revealed a high uptake of the mAbs in the C4-2 tumors at 24 and
      48 hr after tracer injection and only a minimal distribution in the DU 145 tumors
      and other organs. In contrast, the F(ab)(2) and Fab fragments of 3/A12 were
      detected at a high extend in the kidney but not in the C4-2 tumors. These results
      were confirmed by gamma counting of dissected organs after the final imaging.
      CONCLUSIONS: Due to the high and specific uptake of the 64Cu-labeled mAbs in PSMA
      positive tumors, these antibodies represent excellent tools for prostate cancer
      imaging.

PMID- 20687215
TI  - Loss of the matriptase inhibitor HAI-2 during prostate cancer progression.
AB  - BACKGROUND: Prostate cancer progression is accompanied by increased levels of
      extracellular proteases that are capable of remodeling the extracellular matrix
      as well as cleaving and activating growth factors and their receptors that are
      critically involved in pro-cancerous signaling pathways. The membrane anchored
      serine protease matriptase (also known as MT-SP1, epithin, and TADG15) has been
      implicated in prostate cancer. Several studies have demonstrated that the
      expression of this protease, both on the RNA and protein level is significantly
      increased during prostate cancer progression. Hepatocyte activator growth factor
      inhibitor-2 (HAI-2) has recently been identified as a physiological inhibitor of
      matriptase. It has been proposed that the increase of matriptase with a
      concomitant loss of its inhibitors may play a critical role in cancer
      progression. METHODS: In this study, we used immunohistochemistry to determine
      the expression of HAI-2 protein in 136 prostate cancer samples, 20 prostate
      benign prostatic hyperplasia (BPH) samples, and 31 normal or tumor-adjacent
      prostate samples. Specificity of detection was ensured by using two unrelated HAI
      2 antibodies and corresponding non-immune IgG antibodies. RESULTS: We demonstrate
      that HAI-2 protein is significantly decreased in malignant lesions as compared to
      normal and BPH lesions, and that the most poorly differentiated tumors (Gleason
      score 8-10) have the lowest level of HAI-2 expression. CONCLUSION: These data
      suggest that the loss of HAI-2 may be actively involved in prostate cancer
      progression by causing a reduced inhibitory capacity of proteolysis possibly of
      the physiological target for HAI-2 matriptase.

PMID- 20687216
TI  - Immunohistochemical examination of the mTORC1 pathway in high grade prostatic
      intraepithelial neoplasia (HGPIN) and prostatic adenocarcinomas (PCa): a tissue
      microarray study (TMA).
AB  - BACKGROUND: The mammalian target of rapamycin (mTOR) is a serine/threonine
      protein kinase and a key regulator of protein synthesis and growth and is
      upregulated in many cancers. mTOR is activated by AKT phosphorylation (p-mTOR). p
      mTOR associates with regulatory-associated protein of TOR (RAPTOR), forming the
      mTORC1 complex. mTORC1 promotes the activation of p70 ribosomal protein s6 kinase
      1 (p70(S6K1)) and ribosomal protein s6 (RPS6). Upregulation of this pathway can
      lead to an aberrant increase in cell growth and metabolism characteristic of
      malignant transformation. METHODS: This study presents the immunohistochemical
      (IHC) expression of the mTORC1 pathway in prostate neoplasia. The expression of p
      mTOR and RAPTOR and p-p70(S6K1) and p-RPS6 were examined in HGPIN and PCa using
      tissue microarrays (TMA). Since each case in our TMAs was represented by three
      tissue cores, we quantified the IHC intratumoral heterogeneity of mTOR
      expression. This extensive analysis is the first detailed assessment documenting
      the IHC heterogeneity of mTOR expression in HGPIN and prostate cancer and
      represents the first IHC description of the mTORC1 pathway in HGPIN and PCa.
      RESULTS: A Cochran-Armitage analysis demonstrated decreasing p-mTOR activity
      progressing from PIN through GL6 and GL7 to HG PCa. There was considerable
      intratumoral IHC heterogeneity within an individual patient. However, a
      statistically significant correlation was observed between p-mTOR, p-p70(S6K1),
      and p-RPS6 in each representative core. CONCLUSION: mTOR inhibitors may be an
      effective treatment for HGPIN and PCa. The extent of mTOR expression in an
      individual patient would determine the effective use of mTOR inhibitors as a
      potential therapeutic strategy.

PMID- 20687217
TI  - Rh2 or its aglycone aPPD in combination with docetaxel for treatment of prostate
      cancer.
AB  - BACKGROUND: Docetaxel is one of the few chemotherapeutic drugs that are
      considered highly effective when used to treat prostate cancer patients that have
      relapsed and/or metastatic disease, it is therefore reasonable to expect further
      improvements in treatment outcomes when it is combined with other therapeutic
      agents active in prostate cancer. This study assesses the combination of well
      tolerated and orally bioavailable formulations of ginsenoside Rh2 or its aglycone
      aPPD with docetaxel. METHODS: The in vitro activity of Rh2, aPPD, and docetaxel
      was determined in four prostate cancer cell lines: PC-3, LNCaP, DU145, and C4-2.
      Combinations of Rh2 or aPPD with docetaxel were assessed using the constant ratio
      combination design. Combination Indices (CI) and Dose Reduction Indices (DRI)
      were subsequently estimated using Calcusyn. In vivo efficacy studies and
      Immunohistochemical analyses (PC-3 model) were also evaluated. RESULTS: In PC-3,
      DU145 and C4-2 prostate cancer cells combinations of Rh2 or aPPD with docetaxel
      were predominantly additive or synergistic. Combinations of Rh2 + docetaxel and
      aPPD + docetaxel caused established PC-3 tumors to regress from their initial
      size by 15% and 27%, respectively. Tumor cell proliferation rate (measured by Ki
      67 positive cells) was significantly lower for combinations of Rh2 + docetaxel
      and aPPD + docetaxel, compared to animals treated with docetaxel alone.
      CONCLUSIONS: Rh2 and aPPD can be combined with docetaxel to yield additive or
      synergistic activity in vitro and in vivo. Pending further assessment of toxicity
      and pharmacodynamic behavior, this study supports testing of combinations of
      ginsenoside Rh2 or its aglycone aPPD with docetaxel in a clinical setting.

PMID- 20687218
TI  - Vitamin D pathway gene variants and prostate cancer prognosis.
AB  - BACKGROUND: Observational studies linking vitamin D deficiency with increased
      prostate cancer (PCa) mortality and the pleiotropic anticancer effects of vitamin
      D in malignant prostate cell lines have initiated trials examining potential
      therapeutic benefits of vitamin D metabolites. There have been some successes but
      efforts have been hindered by risk of inducing hypercalcemia. A limited number of
      studies have investigated associations between variants in vitamin D pathway
      genes with aggressive forms of PCa. Increased understanding of relevant germline
      genetic variation with disease outcome could aid in the development of vitamin-D
      based therapies. METHODS: We undertook a comprehensive analysis of 48 tagging
      single-nucleotide polymorphisms (tagSNPs) in genes encoding for vitamin D
      receptor (VDR), vitamin D activating enzyme 1-alpha-hydroxylase (CYP27B1), and
      deactivating enzyme 24-hydroxylase (CYP24A1) in a cohort of 1,294 Caucasian cases
      with an average of 8 years of follow-up. Disease recurrence/progression and PCa
      specific mortality risks were estimated using adjusted Cox proportional hazards
      regression. RESULTS: There were 139 cases with recurrence/progression events and
      57 cases who died of PCa. Significantly altered risks of recurrence/progression
      were observed in relation to genotype for two VDR tagSNPs (rs6823 and rs2071358)
      and two CYP24A1 tagSNPs (rs927650 and rs2762939). Three VDR tagSNPs (rs3782905,
      rs7299460, and rs11168314), one CYP27B1 tagSNP (rs3782130), and five CYP24A1
      tagSNPs (rs3787557, rs4809960, rs2296241, rs2585428, and rs6022999) significantly
      altered risks of PCa death. CONCLUSIONS: Genetic variations in vitamin D pathway
      genes were found to alter both risk of recurrence/progression and PCa-specific
      mortality.

PMID- 20687219
TI  - Indoleamine 2,3-dioxygenase (IDO) activity influence tumor growth in the TRAMP
      prostate cancer model.
AB  - BACKGROUND: Indoleamine 2,3-dioxygenase (IDO) activity has been shown to be
      expressed in local lymph nodes and induce immune suppression of tumor immunity.
      Here we analyze the effect of IDO expression on prostate tumor growth using the
      transgenic adenocarcinoma of mouse prostate (TRAMP) animal model. METHODS: Mice
      deficient in IDO expression were crossed to TRAMP mice and the time to the
      appearance of palpable tumors were measured. Immune histology was used to analyze
      the IDO expressing cells in tumors and in local lymph nodes. The levels of the
      substrate for IDO (tryptophane) and its product (kynurenine) was measured by
      HPLC. RESULTS: We found that systemic IDO activity, determined as the
      kynurenine/tryptophan ratio in serum, correlated with the presence of palpable
      tumor. Immunohistological analysis showed increased numbers of IDO expressing
      cells in local lymph nodes. In tumors, IDO expression could be detected in the
      tumor stroma by both CD31+ and CD31(-) cells. Essentially no CD45+, IDO
      expressing cells could be detected in the tumors. The influence of IDO activity
      on tumor progression was analyzed by back-crossing TRAMP mice with IDO(-/-)
      animals and J-chain negative (J(-/-)) mice that have perturbed IDO activity. In
      both crosses a delayed tumor incidence was observed. CONCLUSION: Our results
      argue for a role for IDO mediated immune suppression in the early stages of
      prostate cancer progression. However, since the intra-tumor IDO expression in J(
      /-) mice was indistinguishable from that of C57BL/6 animals the IDO expression in
      the tumor tissue appears to be irrelevant for TRAMP tumor incidence.

PMID- 20687220
TI  - Organ-wide telomeric status in diseased and disease-free prostatic tissues.
AB  - BACKGROUND: Telomere attrition occurs early in the development of prostatic
      adenocarcinoma. However, little is known about either telomere status in benign
      prostatic hyperplasia (BPH), or the spatial and organ-wide distribution of
      potential telomere aberrations throughout all areas of prostatic glands affected
      by cancer or BPH. METHODS: Slot blot titration assay was used to determine
      telomere DNA content (TC), a proxy for telomere length, in macrodissected tissue
      consisting of 54 normal samples from 5 disease-free prostates, 128 BPH samples
      from 4 non-cancerous prostates, and 45 tumor, 73 BPH, and 4 prostatic
      intraepithelial neoplasia (PIN) samples from 5 cancerous prostates. RESULTS:
      Compared to TC in normal prostate samples (n = 54; TC mean = 0.98), tumor samples
      displayed telomere attrition (n = 45; TC mean = 0.67). TC in PIN samples was
      similar to tumors. TC in BPH samples from cancerous prostates was similar to TC
      in tumors and also displayed telomere shortening (n = 73; TC mean = 0.76),
      whereas BPH samples from non-cancerous prostates displayed longer telomeres (n =
      128; TC mean = 1.06). In prostates affected by adenocarcinoma, areas of potential
      telomere attrition occurred in histologically normal tissues through the entire
      gland. However, three-dimensional zoning revealed a pattern of increasing TC as a
      function of distance from the primary (index) tumor. CONCLUSIONS: Spatial
      distributions of TC in prostate specimens indicate a complex "field effect" with
      varying contributions from both cancer and BPH. The observation that telomere
      length variations occur in fields of histologically normal tissues surrounding
      the tumor is of clinical importance, as it may have implications for the
      diagnosis and focal therapy of prostate cancer.

PMID- 20687221
TI  - Fatigue in prostate cancer survivors treated with definitive radiotherapy and
      LHRH analogs.
AB  - BACKGROUND: Few studies have dealt with chronic fatigue (CF) in definitive
      radiotherapy (RAD) patients during and after (neo-)adjuvant androgen deprivation
      therapy (ADT) for prostate cancer. METHODS: CF was the primary outcome in this
      population-based cross-sectional study as evaluated by the Fatigue Questionnaire.
      We compared the post-RAD levels of fatigue in two groups of > or = 1 year
      prostate cancer survivors; those with ongoing medical castration (HTcont) and
      those who had used a luteinizing hormone-releasing hormone analog (LHRHa), but
      had discontinued the therapy at the time of the survey (HTdis). The prevalence of
      CF and the levels of total fatigue were compared to comparable parameters in men
      with prostatic RAD who never had had ADT (Control group) and to men > 60 years
      old from the general population. RESULTS: After an observation time of median 18
      months since start of radiotherapy about 40% of our > or = 1 year prostate cancer
      survivors from the HTcont group reported CF, as compared to approximately a
      quarter of men from the HTdis group and, the prevalence of CF in the latter group
      being similar to that of hormone-naive RAD controls and males from the general
      population. After discontinuation of ADT, age 65 years or below was associated
      with increased risk of CF. CONCLUSIONS: Pre-counseling of prostate cancer
      patients starting (neo-)adjuvant LHRHa therapy must include fatigue, mainly
      physical fatigue, in particular in men aged 65 years or younger. Future studies
      of testosterone recovery after ADT discontinuation should also include measures
      of CF.

PMID- 20687222
TI  - Role of the protein tyrosine phosphatase SHP-1 in Interleukin-6 regulation of
      prostate cancer cells.
AB  - BACKGROUND: Interleukin-6 (IL-6) is a multifunctional cytokine that has been
      implicated in the modulation of growth and progression of prostate cancer.
      Decreased expression of the tyrosine phosphatase SHP-1, involved in regulation of
      cytokine and tyrosine kinase receptor signaling, has been shown to be associated
      with less favorable outcome among prostate cancer patients. METHODS: Parental
      LNCaP cells and an LNCaP-IL6+ subline, derived from parental LNCaP cells by
      continuous culture of the cells in the presence of recombinant IL-6 were used in
      the study. Expression of STAT3, pSTAT3, ERK, pERK, AKT, pAKT, PTEN, and SHP-1 was
      analyzed by immunohistochemistry, Western blots, cDNA microarray, quantitative
      PCRs, and reverse transcriptase PCRs. Proliferation and apoptosis of transfected
      cells were analyzed by caspase3/7 assay and flow cytometry. RESULTS:
      Phosphorylation of ERK and STAT3 was increased in the LNCaP-IL6+ subline compared
      with LNCaP cells, whereas pAKT was decreased. Overexpression and inhibition
      experiments with SHP-1 siRNA showed that SHP-1 reduced proliferation and
      increased apoptosis in both cell lines. Microarray analysis revealed 80 up
      regulated and 87 down-regulated SHP-1-related genes in the LNCaP-IL6+ cell line
      compared with LNCaP cells. CONCLUSIONS: SHP-1 suppresses growth and increases
      apoptosis in both LNCaP and LNCaP-IL6+ cells, which suggests that SHP-1 could be
      a therapeutic target in prostate cancer, even when there is an IL-6-related
      growth advantage.

PMID- 20687223
TI  - MiR-34a attenuates paclitaxel-resistance of hormone-refractory prostate cancer
      PC3 cells through direct and indirect mechanisms.
AB  - BACKGROUND: Patients with hormone-refractory prostate cancer are treated with
      taxane drugs, but eventually become drug resistant. We aimed to elucidate the
      molecular mechanisms underlying paclitaxel resistance of hormone-refractory
      prostate cancer with a special focus on the roles of miR-34a and SIRT1. METHODS:
      Paclitaxel-resistant cells (PC3PR) were generated from hormone-refractory PC3
      cells. The expression levels of mRNA and miRNA were determined by reverse
      transcriptase PCR and those of protein were by Western blot analysis.
      Transfection of miRNA precursor or siRNA was performed using the liposome
      mediated method. RESULTS: MiR-34a over-expression and SIRT1 knockdown attenuated
      paclitaxel resistance of PC3PR cells. MiR-34a expression was reduced in PC3PR
      cells compared with PC3 cells, while the expression levels of HuR and Bcl2 as
      well as SIRT1 were elevated in PC3PR cells. Luciferase reporter assays revealed
      that both SIRT1 3'-UTR and promoter activities were higher in PC3PR cells than in
      PC3 cells. Introduction of miR-34a precursor into PC3PR cells resulted in
      decreases in HuR, Bcl2, and SIRT1 expression and inhibition of the SIRT1 3'-UTR
      activity. HuR knockdown reduced SIRT1 and Bcl2 expression. These results suggest
      that miR-34a not only directly but also indirectly via regulating HuR expression
      acts on the 3'-UTR of SIRT1 and Bcl2 mRNAs, thereby controlling their expression.
      Thus, in PC3PR cells, reduced expression of miR-34a confers paclitaxel resistance
      via up-regulating SIRT1 and Bcl2 expression. CONCLUSIONS: MiR-34a and its
      downstream targets SIRT1 and Bcl2 play important roles in the development of
      paclitaxel resistance, all of which can be useful biomarkers and promising
      therapeutic targets for the drug resistance in hormone-refractory prostate
      cancer.

PMID- 20687224
TI  - Apoptosis regulators Fau and Bcl-G are down-regulated in prostate cancer.
AB  - BACKGROUND: The molecular control of cell death through apoptosis is compromised
      in prostate cancer cells, resulting in inappropriate cell survival and resistance
      to cytotoxic therapy. Reduced expression of the functionally connected apoptosis
      regulators and candidate tumor suppressors Fau and Bcl-G has recently been
      implicated in oncogenesis in other tissues. The present study examines the
      hypothesis that reduced expression of these genes may be involved in prostate
      cancer. METHODS: Fau and Bcl-G mRNA levels were determined by real time RT-PCR in
      two independent prostate tissue collections. In experiments in vitro, Fau and Bcl
      G levels in prostate cancer cell lines were reduced using RNA interference and
      the effects on sensitivity to UVC irradiation were determined. RESULTS: Fau and
      Bcl-G mRNA levels were both lower in prostate cancer tissue than in normal
      prostate and Benign Prostate Hyperplasia. Active down-regulation of Fau and Bcl-G
      expression in vitro resulted in decreased sensitivity to UVC-induced
      cytotoxicity. Simultaneous down-regulation of Fau and Bcl-G produced a decrease
      in sensitivity which was similar to either gene alone. CONCLUSIONS: Fau and Bcl-G
      mRNA levels are both decreased in prostate cancer. In prostate cancer cell lines
      in vitro such down-regulation results in reduced sensitivity to UVC-induced
      cytotoxicity, consistent with the putative roles of these genes as candidate
      prostate tumor suppressors. The absence of an additive effect when Fau and Bcl-G
      were down-regulated simultaneously is consistent with the two genes acting in the
      same apoptosis pathway, for example, with the pro-apoptotic effects of Fau being
      mediated through modulation of Bcl-G.

PMID- 20687225
TI  - An in vitro model for preclinical testing of endocrine therapy combinations for
      prostate cancer.
AB  - BACKGROUND: Even though patients with prostate cancer commonly respond to
      endocrine treatment, in most cases the disease progresses to castration resistant
      prostate cancer (CRPC). Our objective was to generate a novel cell line model
      representing the endocrine treatment naive prostate cancer for testing treatments
      that target the androgen receptor (AR) and androgen metabolism. METHODS: After
      culturing DuCaP cells 20 passages with additional 1 nM R1881, DuCaP-N(aive) cell
      line was developed and validated for testing endocrine therapy combinations. Cell
      viability, apoptosis and cell cycle distribution were assessed in DuCaP and DuCaP
      N when interfering with the hormonal content. RESULTS: Addition of 1 nM R1881 to
      DuCaP reduces cell viability and induces cell cycle inhibition and apoptosis.
      Eventually, an androgen accustomed DuCaP-N cell line developed. An antiandrogen
      (bicalutamide), a histone deacetylase (HDAC) inhibitor (trichostatin A) and a
      5alpha-reductase (SRD5A) inhibitor (finasteride) reduce cell viability, and their
      combinations give a synergistic response in inducing apoptosis. CONCLUSIONS: The
      TMPRSS2-ERG expressing DuCaP-N cell line represents human prostate cancer prior
      to endocrine treatment, and its parental DuCaP cell line is a model for CRPC.
      These cell lines can be used for preclinical evaluation of compounds that target
      the androgenic pathway.

PMID- 20687226
TI  - Muscarinic receptors and their mRNAs in type 2 Goto-Kakizaki diabetic rat
      prostate.
AB  - BACKGROUND: As increasing evidence is pointing towards the relationship between
      diabetes and benign prostatic hyperplasia/lower urinary tract symptoms, we
      investigated the pharmacological properties and gene expressions of the
      muscarinic receptors in type 2 diabetes rat prostate. METHODS: Twelve- and 70
      week-old male Goto-Kakizaki (GK) rats and age-matched male Wistar rats were used
      in this study. The densities of muscarinic receptors (B(max) values) were
      determined by saturation studies with [(3)H]NMS ([N-methyl-(3)H] scopolamine
      methyl chloride) in the prostatic membrane particulates. The participation levels
      of M(1), M(2), and M(3) receptor protein and mRNA levels in the prostate were
      investigated by immunoblot analysis and real-time polymerase chain reaction
      (PCR), respectively. RESULTS: The B(max) values in 12-week-old Wistar and GK, and
      in 70-week-old Wistar and GK rat prostates were 36.0 +/- 2.8, 49.4 +/- 11.4, 22.0
      +/- 2.2, and 47.0 +/- 4.1 fmol/mg protein, respectively. However, there were no
      significant differences in the affinity constants between any groups. Immunoblot
      analysis showed the existence of significant amounts of M(1), M(2), and M(3)
      receptor subtypes in each rat prostate. According to real-time PCR studies the
      rank order of expression levels of muscarinic receptors mRNA subtypes in the
      prostate were M(3) > M(2) > M(1). In each receptor subtype in each group,
      diabetes induced up-regulation of mRNAs while the advanced age of the rats was
      related with down-regulation of mRNAs. CONCLUSIONS: Our data indicated that type
      2 diabetes induced up-regulation and age-related down-regulation of the
      expressions of muscarinic receptors and their mRNAs in the rat prostate.

PMID- 20687227
TI  - Chemoprevention of prostate cancer with lycopene in the TRAMP model.
AB  - BACKGROUND: Dietary lycopene combined with other constituents from whole tomatoes
      was previously found to have greater chemopreventive effects against prostate
      cancer as compared to pure lycopene provided in a beadlet formulation. We
      hypothesized that tomato paste would have greater chemopreventive effects in
      transgenic adenocarcinoma of the mouse prostate (TRAMP) mice relative to
      equivalent lycopene doses provided from lycopene beadlets. METHODS: Fifty-nine
      TRAMP mice were randomized to a control diet or to diets providing 28 mg lycopene
      per kg diet from tomato paste (TP) or from lycopene beadlet (LB), and sacrificed
      at 20 weeks. Prostate histopathology, prostate weight and serum levels of IGF-I
      and IGF binding protein-3 were evaluated. RESULTS: The incidence of prostate
      cancer was significantly decreased in the LB group relative to the control group
      (60% vs. 95%, respectively, P = 0.0197) whereas the difference between the TP and
      control groups was not statistically significant (80% vs. 95%, P = 0.34). There
      was no difference in prostate weights between the groups. Total lycopene levels
      in the serum and prostate tissue were similarly elevated in the LB and TP groups
      relative to the control group. The ratio of 5-cis-lycopene to trans-lycopene in
      the serum was significantly greater in the LB group relative to the TP group (P =
      0.0001). Oxidative DNA damage was significantly reduced in the livers of mice fed
      LB and TP diets relative to the control group. CONCLUSIONS: This preclinical
      trial suggests significant chemopreventive activity with a lycopene beadlet
      enriched diet. The chemopreventive effects of lycopene from beadlets versus whole
      tomato products requires further testing in preclinical and clinical models of
      prostate cancer.

PMID- 20687228
TI  - Glycemic control and prostate cancer progression: results from the SEARCH
      database.
AB  - PURPOSE: Several studies have examined the association between diabetes mellitus
      (DM) and prostate cancer (PCa) risk and progression, however nearly all of these
      studies have compared diabetic versus non-diabetic men. We sought to investigate
      the role of glycemic control, as measured by HbA1c, on PCa aggressiveness and
      prognosis in men with DM and PCa from the Shared Equal Access Regional Cancer
      Hospital (SEARCH) database. METHODS: We identified 247 men in SEARCH with DM and
      a recorded HbA1c value within the 12 months prior to radical prostatectomy
      between 1988 and 2009. We divided these men into tertiles by HbA1c level. The
      associations between HbA1c tertiles and risk of adverse pathology and biochemical
      recurrence were tested using multivariate logistic regression and Cox
      proportional hazards models, respectively. RESULTS: Median HbA1c level was 6.9.
      On multivariate analysis, HbA1c tertiles were predictive of pathological Gleason
      score (P-trend = 0.001). Relative to the first tertile, men in the second (OR
      4.68, P = 0.003) and third tertile (OR 6.60, P < 0.001) were more likely to have
      Gleason score > or = 4 + 3. HbA1c tertiles were not associated with margin
      status, node status, extracapsular extension or seminal vesicle invasion (all P
      trend > 0.2). In the multivariate Cox proportional hazards model, increasing
      HbA1c tertiles were not significantly related to risk of biochemical recurrence
      (P-trend = 0.56). CONCLUSION: Men with higher HbA1c levels presented with more
      biologically aggressive prostate tumors at radical prostatectomy. Although risk
      of recurrence was unrelated to HbA1c levels, further studies are needed to better
      explore the importance of glycemic control on long-term outcomes in diabetic men
      with PCa.

PMID- 20687229
TI  - The effect of estrogen supplementation on cell proliferation and expression of c
      kit positive cells in the rat prostate.
AB  - BACKGROUND: Benign prostatic hyperplasia (BPH) is associated with the
      proliferation of prostate tissue and an increase in smooth muscle tone. However,
      the way in which the hormonal environment affects cell proliferation and
      prostatic interstitial cells (PIC) responsible for the maintenance of the smooth
      muscle tone is not clear. The present study investigated the effect of estrogen
      supplementation on cell proliferation, androgen/estrogen ratio, and expression
      and/or distribution of PIC. METHODS: Male Sprague-Dawley rats were anesthetized
      with isoflurane/oxygen breathing mixture and subcutaneously implanted with
      silastic capsules. These capsules were either empty or filled with a 10 or 20 mg
      of crystalline estrogen. RESULTS: Estrogen exerted a potent effect on ventral
      prostate weight, which was manifested as a significant decrease between controls
      and the E(10)- and E(20)-treated rats. Active cell proliferation detected as Ki67
      positive nuclei was observed in the stromal and epithelial cells of the ventral
      prostatic lobes from estrogen-treated rats and controls. Estrogen supplementation
      caused a significant and dose-dependent increase in prostatic estradiol and
      5alpha-dihydrotestosterone (DHT) concentration but the ratios of either DHT/E(2)
      or E(2)/DHT were not significantly affected. PIC were observed in the region
      between the fibromuscular stroma and the glandular epithelium in all three
      experimental groups. E(20)-treated rats showed a higher expression of PIC than
      controls and E(10)-treated rats. CONCLUSIONS: The present study provides novel
      information regarding the synergistic role of estrogens and androgens in the
      prostate: estrogen may prevent prostatic hyperplasia via mechanisms other than
      affecting cell proliferation or DHT/estrogen ratio.

PMID- 20687230
TI  - Expression and function of ATIP/MTUS1 in human prostate cancer cell lines.
AB  - BACKGROUND: We have previously demonstrated Ang II type 2 (AT(2)-) receptor
      mediated inhibition of EGF-induced prostate cancer cell growth in androgen
      dependent (LNCaP) and independent (PC3) prostate cancer cell lines. METHODS: To
      explore the signaling pathways involved in this inhibitory effect, we examined
      the interaction of the AT(2)-receptor with its novel regulatory partner ATIP
      using real time PCR, over-expression, siRNA and [(3)H]thymidine incorporation
      assays. RESULTS: The results in human prostate cancer cell lines demonstrate the
      presence of ATIP in both cell lines examined, and suggest that (i) the AT(2)
      receptor through an interaction with ATIP mediates an anti-growth factor effect
      in both androgen-dependent and androgen-independent cell lines; (ii) ATIP
      expression decreases as the rate of cell growth and androgen-independence
      increase; and (iii) EGF may act on cell growth in part by reducing the content of
      ATIP present in the cells. CONCLUSIONS: The results support our earlier proposal
      in normal cell lines that ATIP is an important component of the cellular response
      to AT(2)-receptor activation. The results further suggest that a critical level
      of ATIP is required to mediate the effect of AT(2)-receptor activation to inhibit
      EGF mediated increases in cell growth. They also suggest that EGF may in part
      induce cell growth by suppressing the level of ATIP expression.

PMID- 20687231
TI  - Constitutive expression of bioactivating enzymes in normal human prostate
      suggests a capability to activate pro-carcinogens to DNA-damaging metabolites.
AB  - BACKGROUND: The constitutive bioactivating capacity of human prostate may play a
      role in determining risk of adenocarcinoma developing in this tissue. Expression
      of candidate enzymes that convert exogenous and/or endogenous agents into
      reactive DNA-damaging species would suggest the potential to generate initiating
      events in prostate cancer (CaP). METHODS: Normal prostate tissues from UK
      resident Caucasians (n = 10) were collected following either radical retropubic
      prostatectomy (RRP) or cystaprostatectomy (CyP). An analysis of gene and protein
      expression of candidate metabolizing enzymes, including cytochrome P450 (CYP)1A1,
      CYP1A2, CYP1B1, N-acetyltransferase 1 (NAT1), sulfotransferase (SULT)1A1,
      SULT1A3, NAD(P)H:quinone oxidoreductase (NQO1), prostaglandin H synthase 1
      (cyclooxygenase 1; COX1), and CYP oxidoreductase (POR) was carried out.
      Quantitative real-time reverse transcriptase polymerase chain reaction, Western
      blot, and immunohistochemical analysis were conducted. RESULTS: Except for CYP1A1
      and CYP1A2, the metabolizing enzymes examined appeared to be expressed with
      minimal inter-individual variation (in general, approximately two- to fivefold)
      in the expression levels. Enzymes such as CYP1B1 and NQO1 that are capable of
      bioactivating pro-carcinogens to reactive metabolites were readily identifiable
      in human prostate. Immunohistochemical analysis showed that although some
      expression is located in the stroma, the majority is localized to epithelial
      cells lining the glandular elements of the tissue; these are the cells from which
      CaP might arise. CONCLUSION: Constitutive expression of bioactivating enzymes
      confers the potential to convert a range of exogenous and/or endogenous agents to
      reactive species capable of inducing DNA damaging events. These findings suggest
      an organ capability for pro-carcinogen activation that could play an important
      role in the etiology of human CaP.

PMID- 20687232
TI  - Tissue expression of IL16 in prostate cancer and its association with recurrence
      after radical prostatectomy.
AB  - BACKGROUND: Genetic polymorphism located within the IL16 gene has been reported
      to be associated with aggressive prostate cancer (PCa). Our aim was to establish
      whether the tissue expression of IL16 is a prognostic factor of survival in PCa.
      METHODS: The files of patients who underwent radical prostatectomy (RP) between
      1995 and 2001 were reviewed. The cases were selected and classified according to
      the D'Amico classification for risk of recurrence (intermediate or high). The
      value of IL16 and its receptor CCR5 (chemokine (C-C motif) receptor 5) expression
      levels were determined as witness of aggressiveness patterns and markers of
      biological relapse in patients with PCa treated by RP. A tissue microarray of 304
      cases was constructed. IL16 and CCR5 expression levels were characterized by
      immunohistochemistry. RESULTS: IL16 expression was correlated with high Gleason
      score (i.e., >7) (P < 0.01). It was not significant for CCR5. IL16 and CCR5 were
      not associated with prostate-specific antigen (PSA) or capsular extension of the
      disease. The accurate prediction of disease outcome, using stratification of
      cases, according to negative margins and D'Amico classification was significantly
      enhanced by status of IL16 expression (P <= 0.01). In univariate analyses,
      Gleason score, PSA level, stage and loss of IL16 expression were related to
      better biological-free survival (P < 0.05) but not CCR5. In a multivariate
      analysis, IL16 expression, Gleason score, and tumor stage were independent
      factors for biochemical-free survival (P = 0.001). CONCLUSIONS: IL16 appears to
      be a useful prognostic factor in PCa. Its expression in PCa tissue was correlated
      to tumor aggressiveness and biochemical relapse of the disease.

PMID- 20687233
TI  - A thermodynamic characterization of the interaction of 8-anilino-1
      naphthalenesulfonic acid with native globular proteins: the effect of the ligand
      dimerization in the analysis of the binding isotherms.
AB  - 8-Anilino-1-naphthalenesulfonic acid (ANS) is a popular fluorescence probe,
      broadly used for the analysis of proteins, but the nature of its interaction with
      proteins and the high increase in the fluorescence intensity that takes place
      upon such process are still unclear. In the last few years, isothermal titration
      calorimetry has been used to characterize the nature of the interaction of this
      dye with proteins. The analysis of the binding isotherms of these studies has not
      considered the dimerization equilibrium of ANS, which is pH dependent, and it can
      result in serious errors in the data analysis. In the present work we have
      developed a suitable data analysis by which this process is taken into account.
      To study the binding of the dye to proteins at different pH values, we have used
      the Abl-SH3 domain. Our results suggest that at pH 3 and 5, where the
      dimerization of the ANS is important, electrostatic interactions are significant
      for the binding of ANS to the Abl-SH3 domain. However, at pH 7, ANS behaves
      mostly as monomer and the interaction with the protein is mainly hydrophobic. The
      pH dependent behavior of the ANS binding to proteins can be explained in terms of
      ionization states of both, the protein and the ANS.

PMID- 20687234
TI  - Release of phenolic acids from defatted rice bran by subcritical water treatment.
AB  - BACKGROUND: Oil production from rice bran, an undervalued by-product of rice
      milling, produces defatted rice bran (DRB) as a waste material. Although it is
      considered a less valuable product, DRB still contains useful substances such as
      phenolic compounds with antioxidant, UV-B-protecting and anti-tumour activities.
      In this study the phenolic acids in DRB were extracted with subcritical water at
      temperatures of 125, 150, 175 and 200  degrees C. RESULTS: Analysis of total
      phenolics using Folin-Ciocalteu reagent showed about 2-20 g gallic acid
      equivalent kg(-1) bran in the extracts. High-performance liquid chromatography
      analysis showed low contents of phenolic acids (about 0.4-2 g kg(-1) bran).
      Ferulic, p-coumaric, gallic and caffeic acids were the major phenolic acids
      identified in the extracts. Thermal analysis of the phenolic acids was also done.
      The thermogravimetric curves showed that p-coumaric, caffeic and ferulic acids
      started to decompose at about 170  degrees C, while gallic acid did not start to
      decompose until about 200  degrees C. CONCLUSION: Subcritical water can be used
      to hydrolyse rice bran and release phenolic compounds, but the high temperatures
      used in the extraction can also cause the decomposition of phenolic acids.

PMID- 20687235
TI  - Relationships between disease control, green leaf duration, grain quality and the
      production of alcohol from winter wheat.
AB  - BACKGROUND: Since demand for distilling wheat is expected to increase rapidly as
      a result of the development of the bioethanol industry, efficient production will
      become of increasing importance. Achieving this will require an understanding of
      the agronomic factors that influence both grain yield and alcohol yield.
      Therefore five field experiments using the winter distilling wheat variety
      Glasgow were conducted over three seasons (2006-2007, 2007-2008 and 2008-2009) to
      study the relationships between foliar disease and alcohol yield. RESULTS: There
      was a significant relationship between alcohol yield and the severity of the
      disease septoria leaf blotch (Septoria tritici), which was present in the
      experiments from natural infection. Retention of green flag leaf area as affected
      by disease control following fungicide application was also shown to be important
      for achieving high alcohol yields. Measurements of grain quality showed that high
      thousand-grain weight and low grain protein concentration were significantly
      related to increased alcohol yield. CONCLUSION: The experiments showed the
      importance of disease management to protect alcohol yields in the distilling
      wheat crop. Fungicides that provide greater disease control and improved green
      leaf retention are likely to be beneficial to alcohol yield.

PMID- 20687236
TI  - Factors affecting ANKOMTM fiber analysis of forage and browse varying in
      condensed tannin concentration.
AB  - BACKGROUND: Browse species containing condensed tannins (CTs) are an important
      source of nutrition for grazing/browsing livestock and wildlife in many parts of
      the world, but information on fiber concentration and CT-fiber interactions for
      these plants is lacking. RESULTS: Ten forage or browse species with a range of CT
      concentrations were oven dried and freeze dried and then analyzed for ash
      corrected neutral detergent fiber (NDFom) and corrected acid detergent fiber
      (ADFom) using separate samples (ADFSEP) and sequential NDF-ADF analysis (ADFSEQ)
      with the ANKOMTM fiber analysis system. The ADFSEP and ADFSEQ residues were then
      analyzed for nitrogen (N) concentration. Oven drying increased (P < 0.05) fiber
      concentrations with some species, but not with others. For high-CT forage and
      browse species, ADFSEP concentrations were greater (P < 0.05) than NDFom values
      and approximately double the ADFSEQ values. Nitrogen concentration was greater (P
      < 0.05) in ADFSEP than ADFSEQ residues, likely due to precipitation with CTs.
      CONCLUSION: Sequential NDF-ADF analysis gave more realistic values and appeared
      to remove most of the fiber residue contaminants in CT forage samples. Freeze
      drying samples with sequential NDF-ADF analysis is recommended in the ANKOMTM
      fiber analysis system with CT-containing forage and browse species.

PMID- 20687238
TI  - Home phototherapy for psoriasis is cost-effective.

PMID- 20687237
TI  - By the way, doctor.  Last August you wrote about platelet-rich plasma therapy for
      chronic tendon problems.  Has there been any news since then?  I ask because I'm
      thinking about it for my tennis elbow.

PMID- 20687239
TI  - The DDAH-ADMA pathway. Proceedings of the 4th International Symposium on ADMA.
      August 28-30, 2008. Bregenz, Austria.

PMID- 20687241
TI  - Proceedings of the Ninth Symposium on Mass Spectrometry in the Health & Life
      Sciences: Molecular & Cellular Proteomics. August 23-27, 2010. San Francisco,
      California, USA.

PMID- 20687240
TI  - Proceedings of the 10th International Conference on Alzheimer's Drug Discovery.
      September 14-15, 2009. Jersey City, New Jersey, USA.

PMID- 20687242
TI  - Editorial note on the processing, storage, transmission, acquisition, and
      retrieval (P-STAR) of bio, medical, and health information.

PMID- 20687243
TI  - A rigorous mind meets her yielding body: intellectual life and meaning-making in
      Wit.

PMID- 20687244
TI  - Enlisting investigators.
AB  - Few scientists realize that the enormous budget of the US Department of Defense
      includes sizeable funds for basic research. Eric Hand provides a guide for the
      uninitiated.

PMID- 20687245
TI  - Climate change and faunal dynamics in  the uttermost part of the earth.
AB  - To use the 'lessons of the Pleistocene' to forecast the biotic effects of climate
      change, we must parse the effects of history and ecology in the Quaternary
      record. The preponderance of Northern Hemisphere studies of biotic responses to
      climate change provides a limited set of players and environmental circumstances
      with which to decouple these drivers. In this issue Lessa et al. (2010) examine
      population structure in 14 species of mice distributed across Patagonia and
      Tierra del Fuego in southern South America. In the Southern Cone, glacial ice was
      alpine, not polar; major habitats were (and are) oriented N-S, not E-W; and
      habitable land area actually increased, not decreased, at the height of the last
      glacial maximum (LGM). Despite these differences, there is evidence for poleward
      demographic expansion in 10 of the 14 species, and phylogeographic breaks in
      these are likewise stepped by latitude (and presumably history) rather than by
      biome. Nevertheless, high latitude endemism and the antiquity of these lineages
      point to an extended presence in the region that very likely predates the
      Pleistocene.

PMID- 20687246
TI  - Xmrks the spot: life history tradeoffs,  sexual selection and the evolutionary 
      ecology of oncogenesis.
AB  - In a classic paper, George Williams (1957) argued that alleles promoting
      reproductive success early in life may be favoured by selection, even if they
      reduce the lifespan of individuals that bear the allele. A variety of evidence
      supports the theory that such 'antagonistic pleiotropy' is a major factor
      contributing to the evolution of senescence (Ljubuncic & Reznick 2009), but
      examples of specific alleles known to fulfil Williams' criteria remain rare, in
      both humans and other animals (e.g. Alexander et al. 2007; Kulminski et al.
      2010). An intriguing example in this issue of Molecular Ecology (Fernandez &
      Bowser 2010) demonstrates that both natural and sexual selection may favour
      melanoma-promoting oncogene alleles in the fish genus Xiphophorus.

PMID- 20687247
TI  - ACCF/ACR/AHA/NASCI/SAIP/SCAI/SCCT 2010 expert consensus document on coronary
      computed tomographic angiography: a report of the American College of Cardiology
      Foundation Task Force on Expert Consensus Documents.

PMID- 20687248
TI  - Establishment of control site baseline data for erosion studies using
      radionuclides: a case study in East Slovenia.
AB  - The aim of the present study was to establish a reference site and its soil
      characteristics for use of fallout radionuclides in erosion studies in Slovenia.
      Prior to this study, no reference site and baseline data existed for Slovenia for
      this purpose. In the agricultural area of Goricko in East Slovenia, an
      undisturbed forest situated in Salamenci (46 degrees 44'N, 16 degrees 7'E), was
      selected to establish the inventory value of fallout 137Cs and to establish a
      baseline level of multi-elemental fingerprint (major, minor, trace elements
      including heavy metals) and naturally occurring radionuclides in soils. A total
      of 20 soil profiles were collected at four 10 cm depth increments for evaluation
      of baseline level of 137Cs inventory. An exponential distribution for 137Cs was
      found and the baseline level inventory was established at 7300 +/- 2500 Bq m-2
      with a coefficient of variation of 34%. Of this mean present-day inventory,
      approximately 45% is due to the Chernobyl contribution. The physical degradation
      of soils through erosion is linked with biochemical degradation. This study
      introduces an approach to establishment of the naturally occurring radionuclide
      and elemental fingerprints baseline levels at a reference site which can provide
      comparative data to those from neighbouring agricultural fields for assessment of
      soil redistribution magnitude using fallout radionuclides. In addition, this
      information will be used to determine the impact of soil erosion processes and
      agricultural practices on soil quality and redistribution within agricultural
      landscapes in Slovenia.

PMID- 20687249
TI  - 2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM guidelines for the diagnosis and
      management of patients with thoracic aortic disease: executive summary. A report
      of the American College of Cardiology Foundation/American Heart Association Task
      Force on Practice Guidelines, American Association for Thoracic Surgery, American
      College of Radiology, American Stroke Association, Society of Cardiovascular
      Anesthesiologists, Society for Cardiovascular Angiography and Interventions,
      Society of Interventional Radiology, Society of Thoracic Surgeons, and Society
      for Vascular Medicine.

PMID- 20687250
TI  - [Mandatory accident insurance, the accident and the initial medical report].

PMID- 20687252
TI  - Special issue dedicated to Robert F. Furchgott.

PMID- 20687253
TI  - Enhanced QT shortening and persistent tachycardia after generalized seizures.

PMID- 20687256
TI  - The elders.

PMID- 20687258
TI  - [Dr. Kinyoun, a pioneer of plague study in America].
AB  - Joseph James Kinyoun (1860-1919), an American bacteriologist, was the first
      director of NIH (National Institute of Health). His interest in bacteriology and
      the work of isolation of the cholera organism laid the groundwork for the present
      health research program of NIH. In 1900, Kinyoun identified and confirmed the
      diagnosis in an outbreak of plague in San Francisco. In addition, Kinyoun
      contributed a lot in the prevention and antisepsis of diphtheria, the spread of
      knowledge of bacteriology, and research of public health.

PMID- 20687259
TI  - International concern in scientific, industrial, and governmental communities
      over traces of xenobiotics in foods and in both abiotic and biotic environments
      has justified the present triumvirate of specialized publications in the field.
      Forword.

PMID- 20687260
TI  - Reviews of environmental contamination and toxicology. Preface.

PMID- 20687261
TI  - Specialized versus conventional treatment of infertility in Africa: time for a
      pragmatic approach.

PMID- 20687262
TI  - Female genital mutilation among Edo people: the complications and pattern of
      presentation at a pediatric surgery unit, Benin City.
AB  - This prospective study on female genital mutilation among Edo people was based on
      female children and parents who presented on account of it at the University of
      Benin Teaching Hospital, Benin City, Nigeria, between January 2002 and December
      2007. During the period, 51 female children aged 10 days and 18 years presented
      with complications following genital mutilation. Twenty-nine were brought by
      their parents for mutilation while 67 parents interviewed believed strongly on
      female genital mutilation with 47 mothers mutilated. Religio-cultural and
      superstitious beliefs were the main indications and the type of mutilation ranged
      from excision of clitoridal tip in 10 (19.6%) children to complete excision of
      the clitoris, labia minora and inner layer of majora in 7 (13.7%). Complications
      ranged from clitoridal cyst formation in 21 (41.2%) to life threatening
      infections with one mortality due to tetanus infection.

PMID- 20687263
TI  - Experiences of HIV positive mothers who chose not to breastfeed their babies in
      Nigeria.
AB  - HIV positive mothers, who choose not to breastfeed their babies in a
      predominantly breastfeeding community would face a number of barriers. This study
      looked at the experiences of HIV positive mothers who chose the no breastfeeding
      option. Consecutive HIV positive mothers who opted not to breastfeed their
      infants after infant feeding counselling and whose infants were attending the HIV
      programme at the University of Benin Teaching Hospital, Benin City, Nigeria were
      recruited for the study. Disclosure of HIV serostatus and adherence to no
      breastfeeding options were evaluated using an interviewer administered structured
      questionnaire. Of the 62 mothers recruited for the study, 57 (91.94 %) had
      disclosed their serostatus to at least their partners. Most partners 42 (93.33%)
      were supportive while three mothers were divorced following disclosure. Thirteen
      (20.97%) mothers could not comply with no breastfeeding. Non disclosure of
      serostatus, pressure from extended family and token breastfeeding mitigate
      against adhering to no breastfeeding by HIV positive mothers.

PMID- 20687264
TI  - Genital tract abnormalities among female sex workers who douche with lemon/lime
      juice in Nigeria.
AB  - Vaginal douche products have been associated with cervical cancer. We examined
      female sex workers (FSWs) in Nigeria who douche with lemon or lime juice and
      compared the findings with that of nonusers. We obtained Pap smears and performed
      colposcopy of the vulva, vagina and cervix. A total of 374 FSWs comprising 81
      Lemon users (LUs) and 293 non lemon users (NLUs) were examined. Their mean age
      was 27.8 +/- 6.7 (range 16-63) years. At colposcopy, 17 (4.5%) had genital warts
      [LUs 5 (6.2%); NLUs 12 (4.1%); p=0.43], 61 (16.3%) had suspected squamous
      intraepithelial lesions (SILs) [LUs 17 (21.0%); NLUs 44 (15.0%); p=0.20] and 65
      (17.4%) had other findings. Pap smear cytology showed that 87 (24.6%) had SILs
      [LUs 26 (33.3%); NLUs 61 (22.1%); p=0.03]. Lemon/lime use was associated with
      cervical dysplasia after controlling for HIV status (Adjusted OR=1.8; 95% CI, 1.0
      3.0). Our data suggests an association between the practice of douching with
      citrus juice and cervical dysplasia.

PMID- 20687265
TI  - Faced with a double-edged risk: Ugandan university students' perception of the
      emergency contraceptive pill in Uganda.
AB  - Whereas in high-income countries potential users of Emergency Contraception (EC)
      have information and access to emergency contraceptive pills (ECPs), it has
      remained secretive in low-income countries like Uganda. Although several studies
      have been conducted in relation to EC, few have addressed users' perceptions. The
      objective of our study was to explore perceptions of EC by university students in
      Kampala, Uganda. Seven focus group discussions and four key informant interviews
      were conducted at Makerere University, Kampala. The transcribed data was analyzed
      for content and recurrent themes. Participants expressed ambivalence about ECPs.
      The method was generally recommended but only to the "right people", in this
      context being those aged eighteen years and more. There were reservations
      surrounding provision of ECPs like similarity with abortion and fear of side
      effects. Users' and potential-users' perceptions are crucial in the accessibility
      and utilization of ECPs.

PMID- 20687266
TI  - Coping strategies of young mothers at risk of HIV/AIDS in the Kassena-Nankana
      district of Northern Ghana.
AB  - This qualitative study draws on interpretative principles with emphasis on
      understanding young mothers' vulnerability to HIV/AIDS and explores coping
      strategies used to mitigate risk of infection in a poor rural setting of Ghana.
      Young mothers in their mid-twenties to early thirties and their male partners
      were purposively selected with the assistance of key informants for repeated semi
      structured interviews. Respondents included those in monogamous and polygynous
      marriages with two or more living children, and those with and without formal
      education. Young mothers in this study setting are confronted with complex
      realities as childbearing obligations make protective sex less optional. However,
      more assertive women insist their husbands use condoms when they perceive
      themselves at risk. We conclude that the advent of HIV may advance the cause of
      women's reproductive health empowerment by providing women with very strong
      reasons to minimize HIV risk within marriage.

PMID- 20687267
TI  - Acceptability of child adoption as management option for infertility in Nigeria:
      evidence from focus group discussions.
AB  - Infertility remains a global health challenge with devastating psycho-social
      consequences in many African communities. Adoption that may serve as an
      alternative strategy for the affected couples is not widely practiced. This study
      was conceptualized to assess the acceptability of child adoption as a management
      option by Nigerians. Twelve focus group discussions were held involving three
      communities stratified into inner core, transitory and peripheral, within Ibadan
      metropolis, South-Western Nigeria from May to July 2008. The participants were
      purposively selected based on gender and age group. The barriers mentioned were
      cultural practices, stigmatization, financial implications, and procedural bottle
      necks. Measures suggested to curb these negative attitudes were advocacy,
      community mobilization and enactment of supportive law that will protect all
      parties involved.

PMID- 20687268
TI  - Level and differentials of fertility in Awassa town, Southern Ethiopia.
AB  - A cross-sectional, descriptive study with internal comparison was conducted among
      1376 women of reproductive age with the objective of assessing the level and
      determinants of fertility in Awassa town, Ethiopia. Total Fertility Rate (TFR)
      was 3.4 and the mean Child Ever Born (CEB) was 1.72 and 3.02 among all women and
      married women. Regarding proximate determinants of fertility, the mean age at
      first marriage and duration of postpartum infecundability were 17.75 years and
      12.3 months, respectively. Further, Contraceptive Prevalence Rate among married
      women was 41.2% and Total Abortion Rate was 0.02. Sociodemographic
      characteristics of mothers like poor educational status, absence of income, rural
      place of birth, early marriage, and other variables like history of child death,
      negative husbands' attitude towards contraceptive use, poor educational status of
      husbands, need for additional children, were found to have significant
      association with high fertility; accordingly, these variables need to addressed
      in activities against high fertility.

PMID- 20687269
TI  - The effect of endometrial thickness on in vitro fertilization (IVF)-embryo
      transfer/intracytoplasmic sperm injection (ICSI) outcome.
AB  - The value of measuring the endometrial thickness and studying the endometrial
      receptivity in the context of assisted conception remains a contentious issue. A
      prospective analysis was carried out to determine the effect of endometrial
      thickness on IVF - embryo transfer/ICSI outcome in dedicated Assisted
      Reproductive Technology (ART) units in Abuja and Rivers State, Nigeria. Two
      hundred and fifty one patients who met the inclusion criteria were analysed. They
      were grouped on the basis of endometrial thickness into 3 groups; <7 mm, 7 - 14
      mm and >14 mm. The main outcome measure was clinical pregnancy. There were
      significantly more pregnancies in the 7 - 14 mm endometrial thickness group
      compared to the <7 mm and >14 mm groups, p=0.004 and p<0.0001 respectively. The
      findings suggest that following IVF/ICSI, significantly more pregnancies occurred
      when the endometrial thickness was between 7 and 14 mm.

PMID- 20687270
TI  - Contraceptive use by women in Accra, Ghana: results from the 2003 Accra Women's
      Health Survey.
AB  - The study was to determine the predictors of use of modern contraception among
      women in Accra, Ghana. Data were collected by trained interviewers using
      questionnaires. Complete data for 2199 women were analysed using Stata 8.2. The
      study showed that educational status was the most significant predictor of
      contraceptive use. Women with no formal education had a 48% reduction in the odds
      of having ever used contraception and a 66% reduction in the odds of currently
      using contraception. Regular use of health facilities did not affect
      contraceptive use. Female education should continue to be a priority of the
      Ghanaian government. Education about family planning and the effects of having
      large families should be integrated into the school curriculum. Ghanaian health
      workers need to be active in promoting the use of modern contraceptive methods.

PMID- 20687271
TI  - Risky sexual behaviours among adolescents in Owerri Municipal: predictors of
      unmet family health needs.
AB  - This study examined the risky sexual behaviours (RSBs) of adolescents in Owerri
      Municipal in Imo State. Adopting the descriptive Survey research design, a
      stratified sampling technique was used to enroll 1008 adolescents aged 10 - 19
      from 4 secondary schools into the study. A structured questionnaire was used for
      data collection. Result shown that majority of the adolescent (47.4%) have had
      sex and many have engaged in one form of RSBs or another. Peer group seem to be
      major source of the sexuality information (55.6%) and influencing factor (52.3%).
      Significant association was found to exist between adolescents RSBs and age at
      first sexual experience or adolescent perception of parental rearing pattern
      (p<.05). The study challenged the stake holders involved in the inculcation of
      values, curriculum design or policy formulation to provide appropriate, time
      sensitive and scientifically sound sexuality information for adolescents.

PMID- 20687272
TI  - Bride price and sexual risk taking in Uganda.
AB  - This study assessed the relationship of bride price to sexual risk taking based
      on a large, population-based survey. Data were collected on bride prices for 592
      married women in 12 districts in Uganda in 2001. Controlling for covariates, we
      found that having had a bride price significantly lowered the wife's odds of
      sexual intercourse with a partner other than the spouse (OR= 0.222; 95% CI=
      0.067, 0.737). Controlling for covariates, bride price increased the husband's
      odds of non-spousal sexual intercourse (OR=1.489; 95% CI= 0.746, 2.972), although
      this finding is not statistically significant. Bride price payment is
      statistically significantly associated with lower rates of non-spousal sexual
      contact in women, but is not statistically significantly associated with higher
      rates in men.

PMID- 20687273
TI  - Fertility and occupational hazards: review of the literature.
AB  - Workplace exposures and hazards have detrimental effects on many organ systems in
      the body including the reproductive system. The evidence of the reproductive
      effects of occupational hazards is obtained through a synthesis of the available
      literature. These effects vary and overlap due to the multiple nature of
      exposures in the workplace. Hazardous agents include pesticides, solvents and
      heavy metals. The reproductive effects include reduced fecundity, abnormal sperm
      quality, increased risk of low birth weight, miscarriages and permanent
      sterility. These problems are not readily identified as having occupational
      causes in developing countries such as Nigeria where infertility has a high
      family and social consequence. Epidemiological studies in Nigeria are needed to
      evaluate the reproductive effects of workplace exposures. Protective measures
      such as proper house keeping, education and the use of personal protectives at
      the workplace are advocated.

PMID- 20687274
TI  - Advanced alveolar rhabdomyosarcoma of the uterus: a case report.
AB  - Alveolar rhabdomyosarcoma is an uncommon malignant soft tissue tumour rarely
      found in the female genital tract and carries a very poor prognosis especially in
      adults. A 44 year old premenopausal woman was evaluated for a lower abdominal
      mass, intermittent unprovoked vaginal bleeding and weight loss. Examination
      showed a huge abdomino-pelvic mass, and an irregular cauliflower mass protruding
      from the cervix, from which a biopsy was taken. Exploratory laparotomy revealed a
      widespread disseminated uterine tumour with an "omental cake" and involving
      virtually all the abdominal viscera. Debulking surgery was found to be non
      beneficial and uterine and omental biopsies were taken. The cervical, uterine and
      omental biopsies were all diagnosed alveolar rhabdomyosarcoma. Neither
      chemotherapy nor radiotherapy could be started before the client died of
      fulminant neoplastic dissemination 17 days postoperatively. While the optimal
      management of this rare tumour is unknown, early recognition and diagnosis, and a
      prompt multimodality treatment approach of surgery, chemotherapy and radiotherapy
      offers the best chance of cure.

PMID- 20687275
TI  - Minimization of displacement estimation bias due to high amplitude-reflections
      using envelope-weighted normalization.
AB  - In elastography, displacement estimation is often performed using cross
      correlation-based techniques, assuming fully-developed, homogeneous speckle. In
      the presence of a local, large variation in echo amplitude, such as a reflection
      from a vessel wall, this assumption does not hold true, resulting in a biased
      displacement estimate. Normalizing the echo by its envelope before displacement
      estimation reduces this effect at the cost of larger jitter errors. An algorithm
      is proposed to reduce amplitude-dependent bias in displacement estimates while
      avoiding a large increase in the jitter error magnitude. The algorithm involves
      'Envelope-Weighted Normalization' (EWN) of echo data before displacement
      estimation. A parametric analysis was conducted to find the optimum parameters
      with which this technique could be implemented. The EWN technique was found to
      significantly reduce the rms error of the displacement estimates, showing the
      greatest improvements when utilizing longer window lengths and higher ultrasonic
      frequencies.

PMID- 20687276
TI  - Effects of ultrasound-induced inertial cavitation on enzymatic thrombolysis.
AB  - Cavitation induced by ultrasound enhances enzymatic fibrinolysis by increasing
      the transport of reactants. However, the effects of cavitation need to be fully
      understood before sonothrombolysis can be applied clinically. In order to
      understand the underlying mechanisms, we examined the effects of combining
      ultrasound, microbubbles and thrombolytic enzymes on thrombolysis. First, we
      evaluated the relations between inertial cavitation and the reduction in the
      weight of a blood clot. Inertial cavitation was varied by changing the amplitude
      and duration of the transmitted acoustic wave as well as the concentration of
      microbubbles used to induce cavitation. Second, we studied the combined effects
      of streptokinase and inertial cavitation on thrombolysis. The results show that
      inertial cavitation increases the weight reduction of a blood clot by up to
      33.9%. With linear regression fitting, the measured differential inertial
      cavitation dose and the weight reduction had a correlation coefficient of 0.66.
      Microscopically, enzymatic thrombolysis effects manifest as multiple large
      cavities within the clot that are uniformly distributed on the side exposed to
      ultrasound. This suggests that inertial cavitation plays an important role in
      producing cavities, while microjetting of the microbubbles induces pits on the
      clot surface. These observations preliminarily demonstrate the clinical potential
      of sonothrombolysis. The use of the differential inertial cavitation dose as an
      indicator of blood clot weight loss for controlled sonothrombolysis is also
      possible and will be further explored.

PMID- 20687277
TI  - Novel spline-based approach for robust strain estimation in elastography.
AB  - Robust strain estimation is important in elastography. However, a high signal-to
      noise ratio (SNR) and contrast-to-noise ratio (CNR) are sometimes attained by
      sacrificing resolution. We propose a least-squares-based smoothing-spline strain
      estimator that can produce elastograms with high SNR and CNR without significant
      loss of resolution. The proposed method improves strain-estimation quality by
      deemphasing displacements with lower correlation in computing strains. Results
      from finite-element simulation and phantom-experiment data demonstrate that the
      described strain estimator provides good SNR and CNR without degrading
      resolution.

PMID- 20687278
TI  - Elastography using harmonic ultrasonic imaging: a feasibility study.
AB  - Tissue Harmonic Imaging (THI) is a relatively new modality that has had a
      significant impact in the ultrasound field. In the recent past, imaging the
      mechanical properties of tissues using elastography has also gained great
      interest. In this paper, we investigate the feasibility of combining these two
      state-of-the-art ultrasound-imaging modalities. The performance of elastograms
      obtained using harmonic ultrasonic signals is studied with simulations and
      compared to the performance of conventional elastograms using standard
      statistical methods. Experiments are used as a proof of the technical feasibility
      of generating tissue-harmonic elastograms using experimental harmonic signals.
      The results of our simulation study indicate that all image quality factors
      considered in this study (elastographic signal-to-noise ratio, elastographic
      contrast-to-noise ratio and spatial resolution) may be improved when using
      harmonic ultrasonic signals, provided that the ultrasound system is characterized
      by high bandwidth, high sampling frequency and large lateral sampling.
      Preliminary experimental results suggest that it is technically feasible to
      generate experimental elastograms using harmonic signals, provided that the
      sonographic signal-to-noise ratio of the pre- and postcompression harmonic frames
      is sufficiently high to guarantee reliable values of correlation.

PMID- 20687279
TI  - Simulation of autonomous robotic multiple-core biopsy by 3D ultrasound guidance.
AB  - An autonomous multiple-core biopsy system guided by real-time 3D ultrasound and
      operated by a robotic arm with 6+1 degrees of freedom has been developed. Using a
      specimen of turkey breast as a tissue phantom, our system was able to first
      autonomously locate the phantom in the image volume and then perform needle
      sticks in each of eight sectors in the phantom in a single session, with no human
      intervention required. Based on the fraction of eight sectors successfully
      sampled in an experiment of five trials, a success rate of 93% was recorded. This
      system could have relevance in clinical procedures that involve multiple needle
      core sampling such as prostate or breast biopsy.

PMID- 20687280
TI  - Cuts that will cost lives.

PMID- 20687281
TI  - RCN aims to save jobs and protect services in the face of cuts.

PMID- 20687282
TI  - Ready for Ramadan.
AB  - As the Islamic holy month of Ramadan approaches, one cancer nurse is alerting
      Muslim patients to the risks of discontinuing treatment.

PMID- 20687283
TI  - For Queen and community.
AB  - Since the reintroduction of the title Queen's Nurse in 2007, more than 100
      professionals have received the accolade.

PMID- 20687284
TI  - Charity began at home.
AB  - As a result of her nursing work, Patricia Leathem set up the charity Against
      Breast Cancer, which now has its own research team.

PMID- 20687285
TI  - Reject demonisation.

PMID- 20687286
TI  - Why did baby die?

PMID- 20687287
TI  - Simple strategy helped patient handle short-term memory loss.

PMID- 20687288
TI  - Medicines management: where do I stand if patients have no drug chart?

PMID- 20687289
TI  - Providing contact cards for relatives following bereavement.
AB  - This article describes the implementation of a Welsh Assembly Government policy
      to improve customer service and provide an opportunity for relatives to seek
      further information about the death of a loved one in an acute hospital setting.
      A new relative-centred pathway has been developed. It offers a single point of
      contact for recently bereaved relatives and provides an opportunity to discuss
      any concerns or anxieties in relation to the care and/or treatment in the final
      hours of their loved one's life. The pathway includes a contact card with the
      name and number of a designated person and is a more informal, empathetic and
      person-centred service than the formal complaint process.

PMID- 20687290
TI  - A patient-centred approach to day surgery nursing.
AB  - The pursuit of greater efficiency in modern day surgery has led to the adoption
      and development of many new and extended nursing roles. Such roles often focus on
      physiological measurement to ensure patient safety before and during surgery.
      However, studies suggest that patients require considerable care in relation to
      the social and psychological effect of hospital admission, general anaesthesia,
      surgery and discharge. This article discusses the effect of modern day surgery on
      nurses' practice and concludes by outlining the psychological care need of
      patients undergoing elective day and short stay surgery.

PMID- 20687291
TI  - Effective psychological care for physically ill patients in hospital.
AB  - This article introduces the concept of psychological care as part of a holistic
      approach to nursing practice. Its primary focus is on the psychological care
      needs of general medical and surgical patients in hospital, but the principles
      introduced and discussed are broadly relevant to a wide range of nursing and
      healthcare settings and contexts.

PMID- 20687293
TI  - Right on the button.

PMID- 20687292
TI  - Plaster casting.

PMID- 20687294
TI  - Safety in numbers.

PMID- 20687295
TI  - A grand opportunity.

PMID- 20687296
TI  - Oral microbiology: past, present and future.
AB  - Since the initial observations of oral bacteria within dental plaque by van
      Leeuwenhoek using his primitive microscopes in 1680, an event that is generally
      recognized as the advent of oral microbiological investigation, oral microbiology
      has gone through phases of "reductionism" and "holism". From the small beginnings
      of the Miller and Black period, in which microbiologists followed Koch's
      postulates, took the reductionist approach to try to study the complex oral
      microbial community by analyzing individual species; to the modern era when oral
      researchers embrace "holism" or "system thinking", adopt new concepts such as
      interspecies interaction, microbial community, biofilms, poly-microbial diseases,
      oral microbiological knowledge has burgeoned and our ability to identify the
      resident organisms in dental plaque and decipher the interactions between key
      components has rapidly increased, such knowledge has greatly changed our view of
      the oral microbial flora, provided invaluable insight into the etiology of dental
      and periodontal diseases, opened the door to new approaches and techniques for
      developing new therapeutic and preventive tools for combating oral polymicrobial
      diseases.

PMID- 20687297
TI  - Osteocyte remodeling of the perilacunar and pericanalicular matrix.
AB  - With additional functions of osteocytes being identified, the concept that
      osteocytes are just "static lacunar-dwelling cells" is no longer accepted. We
      reviewed most of the relevant literature on osteocyte's function in the direct
      remodeling of the perilucunar matrix, discussing the advantages and
      disadvantages. Special attention was paid to how the negative researchers argue
      about the "osteocytic osteolysis" principle, and how the positive side addressed
      the arguments. We also discussed the newly found data of osteocytic remodeling
      function from our group. With more biotechnology in hand, there is increased
      excitement in the prospect of now being able to answer the two important
      questions: do osteocytes have the capability to remove mineral from the
      perilacunar matrix and if so what are the molecular and cellular mechanisms? do
      osteocytes have the capability to deposit new mineral on the perilacunar matrix
      and if so what are the cellular and molecular mechanisms?

PMID- 20687298
TI  - Preparing health professionals to provide care to individuals with disabilities.
AB  - AIM: To review the perceptions of dental/medical educators and their students in
      the United States on the adequacy of didactic and clinical preparation to provide
      service for individuals with disabilities. METHODOLOGY: An e-mailed questionnaire
      with follow-up was sent to 198 deans of dental/medical schools, 1,628 directors
      of residency programs in nine medical/dental residency programs, 427 medical
      students in 12 medical schools, and 368 health related organizations, facilities
      and programs. RESULTS: More than half (58%) of the responding deans of reported
      that a curriculum for patients with disabilities was not a high priority at their
      school. A majority (61%) of deans of medical schools, and 47% of the deans of
      dental schools, reported that their graduates were competent to treat patients
      with disabilities. However, majorities of dental/medical school seniors and
      graduates expressed inadequate competency in the care of these patients. A
      majority of the directors of medical/dental residencies indicated a need for
      additional training for their residents. CONCLUSION: There is need for increased
      didactic and clinical preparation of dental/medical school graduates in the care
      of individuals with special health needs. The interest expressed by health
      profession educators in an effort to develop appropriate curriculum modules
      provides an opportunity to prepare new graduates for the care of an increasing
      population of individuals with disabilities.

PMID- 20687299
TI  - HSP25 affects the proliferation and differentiation of rat dental follicle cells.
AB  - AIM: To detect the expression of HSP25 in rat dental follicles both in vivo and
      vitro, and explore the underlying mechanism of HSP25 on the proliferation and
      differentiation of rat dental follicle cells (DFCs). METHODOLOGY:
      Immunohistochemistry was performed to detect the expression of HSP25 in mandibles
      of postnatal rats on days 1, 3, 5, 7, 9 and 11 in vivo. In vitro, the expression
      of HSP25 in DFCs was detected by an indirect immunofluorescence assay. Thiazolyl
      blue tetrazolium bromide (MTT) assay, flow cytometry and alkaline phosphatase
      (ALP) assay were used to identify the time-course effect mediated by different
      concentrations of recombinant murine HSP25 of 0, 1, 10, 50 and 100 ng/mL on rat
      DFCs. RESULTS: Expression of HSP25 was not detected in dental follicles of the
      rats until day 5 after birth, but became up-regulated in a time-dependent manner
      till day 11. HSP25 was detected in the cytoplasm of cultured rat DFCs. No
      significant difference could be observed in the proliferation of DFCs after
      stimulation with different concentrations of HSP25 on days 1, 2 and 3 (P > 0.05).
      HSP25 at concentrations of 50 ng/mL and 100 ng/mL up-regulated the ALP activity
      of DFCs on day 9 (P < 0.05). CONCLUSION: HSP25-immunoreactivity increased
      chronologically during the development of dental follicles. The protein had no
      significant effect on cell proliferation but may play a role in
      cementoblast/osteoblast differentiation of DFCs.

PMID- 20687300
TI  - DAPT enhances the apoptosis of human tongue carcinoma cells.
AB  - AIM: To investigate the effect of DAPT (gamma-secretase inhibitor) on the growth
      of human tongue carcinoma cells and to determine the molecular mechanism to
      enable the potential application of DAPT to the treatment of tongue carcinoma.
      METHODOLOGY: Human tongue carcinoma Tca8113 cells were cultured with DAPT. Cell
      growth was determined using Indigotic Reduction method. The cell cycle and
      apoptosis were analyzed by flow cytometry. Real-time PCR and Immuno-Fluorescence
      (IF) were employed to determine the intracellular expression levels. RESULTS:
      DAPT inhibited the growth of human tongue carcinoma Tca8113 cells by inducing G0
      G1 cell cycle arrest and apoptosis. The mRNA levels of Hairy/Enhancer of Split-1
      (Hes-1), a target of Notch activation, were reduced by DAPT in a dose-dependent
      manner. Coincident with this observation, DAPT induced a dose-dependent promotion
      of constitutive Caspase-3 in Tca8113 cells. CONCLUSION: DAPT may have a
      therapeutic value for human tongue carcinoma. Moreover, the effects of DAPT in
      tumor inhibition may arise partly via the modulation of Notch-1 and Caspase-3.

PMID- 20687302
TI  - Manufacture and cytotoxicity of a lead-free piezoelectric ceramic as a bone
      substitute-consolidation of porous lithium sodium potassium niobate by cold
      isostatic pressing.
AB  - AIM: The piezoelectric properties and cytotoxicity of a porous lead-free
      piezoelectric ceramic for use as a direct bone substitute were investigated.
      METHODOLOGY: Cold isostatic pressing (CIP) was applied to fabricate porous
      lithium sodium potassium niobate (Li0.06Na0.5K0.44) NbO3 specimens using a pore
      forming method. The morphologies of the CIP-processed specimens were
      characterized and compared to those of specimens made by from conventional
      pressing procedures. The effects of the ceramic on the attachment and
      proliferation of osteoblasts isolated from the cranium of 1-day-old Sprague
      Dawley rats were examined by a scanning electron microscopy (SEM) and
      methylthiazol tetrazolium (MTT) assay. RESULTS: The results showed that CIP
      enhanced piezoelectricity and biological performance of the niobate specimen, and
      also promoted an extracellular matrix-like topography of it. In vitro studies
      showed that the CIP-enhanced material had positive effects on the attachment and
      proliferation of osteoblasts. CONCLUSION: Niobate ceramic generated by CIP shows
      a promise for being a piezoelectric composite bone substitute.

PMID- 20687301
TI  - The effect of simvastatin on mRNA expression of transforming growth factor-beta1,
      bone morphogenetic protein-2 and vascular endothelial growth factor in tooth
      extraction socket.
AB  - AIM: To determine the effect of local simvastatin application on the mRNA
      expression level of transforming growth factor-beta1 (TGF-beta1), bone
      morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF) in
      the tooth sockets of rat. METHODOLOGY: Forty-eight male Wistar rats were randomly
      divided into experimental and control groups (n = 24). Polylactic
      acid/polyglycolic acid copolymer carriers, with or without simvastatin, were
      implanted into extraction sockets of right mandibular incisors. The expression of
      TGF-beta1, BMP-2 and VEGF mRNA was determined by in situ hybridization in the
      tooth extraction socket at five days, one week, two weeks and four weeks after
      implantation. RESULTS: The fusiform stroma cells in the tooth extraction socket
      began to express TGF-beta1, BMP-2 and VEGF mRNA in both experimental and control
      groups from one week after tooth extraction until the end of experiment. The
      expression of TGF-beta1 and BMP-2 mRNA in the experimental group was
      significantly up-regulated after one, two and four weeks, and expression of VEGF
      mRNA was significantly increased after one and two weeks compared with that in
      the control group. CONCLUSION: The findings indicate that local administration of
      simvastatin can influence alveolar bone remodeling by regulating the expression
      of a school of growth factors which are crucial to osteogenesis in the tooth
      extraction socket.

PMID- 20687303
TI  - Sharing a commitment on the world stage: the International Year of the Nurse.

PMID- 20687304
TI  - Determinants of premature infant pain responses to heel sticks.
AB  - The exposure of premature infants to stressors, such as pain intended to ensure
      their survival, may instead alter their brain development and contribute to
      several learning and behavioral difficulties observed in later childhood. The
      objective of this descriptive, cross-sectional study was to compare the pain
      responses of 72 preterm infants to a heel stick procedure taking into
      consideration a variety of factors, including the use of opioids and sedatives.
      The pain scores assessed on the Preterm Infant Pain Profile (PIPP) scale were
      highest for the lowest gestational age (GA) group. Multiple linear regression
      analysis with the four predictor variables noted to be correlated with the PIPP
      scores (GA, type of needle, severity of illness, and behavioral state) indicated
      a significant overall relationship (F [5/66] = 5.62, p < 0.01) and accounted for
      44% of the variance. All but severity of illness did not add significantly to the
      variance. Gender, postnatal age, amount, opioids, and sedatives used were not
      correlated to the PIPP scores. It was concluded that sick premature infants and
      those who have been exposed to a variety of painful procedures may not manifest
      behavioral or physiological signs of pain, but may be the most to benefit from
      precise pain assessment and prudent management.

PMID- 20687305
TI  - The effect of music reinforcement for non-nutritive sucking on nipple feeding of
      premature infants.
AB  - In this randomized, controlled multi-site study, the pacifier-activated-lullaby
      system (PAL) was used with 68 premature infants. Dependent variables were (a)
      total number of days prior to nipple feeding, (b) days of nipple feeding, (c)
      discharge weight, and (d) overall weight gain. Independent variables included
      contingent music reinforcement for non-nutritive sucking for PAL intervention at
      32 vs. 34 vs. 36 weeks adjusted gestational age (AGA), with each age group
      subdivided into three trial conditions: control consisting of no PAL used vs. one
      15-minute PAL trial vs. three 15-minute PAL trials. At 34 weeks, PAL trials
      significantly shortened gavage feeding length, and three trials were
      significantly better than one trial. At 32 weeks, PAL trials lengthened gavage
      feeding. Female infants learned to nipple feed significantly faster than male
      infants. It was noted that PAL babies went home sooner after beginning to nipple
      feed, a trend that was not statistically significant.

PMID- 20687306
TI  - Parental satisfaction with nurse's communication and pain management in a
      pediatric unit.

PMID- 20687308
TI  - The developmental origins of health and disease hypothesis.

PMID- 20687307
TI  - Parental influences on adolescent decision making and contraceptive use.
AB  - This article reviews the literature in the area of parental and maternal
      influences on contraceptive decision making, thus determining future directions
      of research and potential interventions. A review of published literature using
      PubMed, CINAHL, Infotrak, Science and Technology, and Medline spanning 1980-2007
      was used to gather information. Results from 35 research studies and 15 scholarly
      articles were included. The search terms adolescent decision making, maternal
      influences on adolescent contraceptive decision making, adolescent contraceptive
      decision making, paternal influences on adolescent decision making, and
      contraception were used to gather data. The literature reveals there is an
      association between parental communication, parenting style, and adolescent
      sexual activity and contraception use. Maternal communication has been shown to
      delay sexual intercourse and increase contraceptive use. Maternal communication
      has rich potential as an intervention to impact positive adolescent sexual
      decision making and contraception use. Gaps in the research identified were the
      lack of studies on the influences on parenting style and the father/adolescent
      influences on sexual initiation and contraceptive decision making.

PMID- 20687309
TI  - Strengthening patient- and family-centered care: learning through webinars.

PMID- 20687310
TI  - Uncomplicated treatment of ankylosed maxillary permanent canine: a case report.
AB  - This report describes the treatment of a young male patient with an ankylosed
      canine which had a high buccal position and during the fixed orthodontic therapy
      it was attempted to bring it into occlusion. This was finally accomplished by
      surgical luxation and extrusion of the tooth.

PMID- 20687311
TI  - Retrospective evaluation of facial soft tissue cephalometric parameters in
      adolescents with normal occlusion.
AB  - Facial soft tissue cephalometric parameters are specific to each society. These
      measurements should be considered during planning treatment for orthodontic
      patients. We establish lateral cephalometric facial soft tissue norms in
      adolescent boys and girls with normal occlusion in Mashhad in the northeast of
      Iran, and compare them with those of other societies.

PMID- 20687312
TI  - Craniofacial changes in patients with Class III malocclusion treated with the
      RAMPA system.
AB  - OBJECTIVE: The underlying etiology of Class III malocclusion may be associated
      with cranial base morphology. The aim of this study is to test the efficacy of a
      Right-Angled Maxillary Protraction Appliance (RAMPA) System in Asian subjects
      with Class III malocclusions. MATERIALS AND METHODS: 27 homologous landmarks were
      digitized from lateral cephalographs for 10 pre-pubertal Japanese children (mean
      age 95 months) with skeletal Class III malocclusion prior to and after RAMPA
      treatment. The mean, pre- and post-treatment craniofacial configurations were
      computed using Procrustes superimposition, and subjected to principal components
      analysis (PCA), and finite-element analysis (FEA). RESULTS: The mean treatment
      time was 22.5 months. All patients showed significant craniofacial change with
      correction of anterior and/or posterior crossbite. The mean, pre- and post
      treatment craniofacial configurations were statistically different when tested
      using PCA (p < 0.001), with the first two principal components accounting for 97%
      of the total shape change. Using FEA, the anterior cranial base showed a relative
      12-32% increase in size. The midfacial and mandibular regions, as well as the
      oropharyngeal airway showed large relative size-changes. CONCLUSION: This study
      suggests that the anterior cranial base may be targeted in the correction Class
      III malocclusions.

PMID- 20687313
TI  - A novel approach in treatment of maxillary deficiency by reverse chin cup.
AB  - The aim of this study was to evaluate the effectiveness of a newly designed small
      sized extraoral appliance on Class III malocclusion and maxillary deficiency in
      growing patients. The case series included 10 patients (4 males, 6 females) with
      a mean age of 8.9 +/- 1.72 years who suffered from maxillary deficiency. All the
      patients were treated with an extra oral appliance which was named as reverse
      chin cup. This appliance consisted of a high pull cap, a chin cup with two
      vertical hooks, a removable appliance on the upper jaw, and two elastics which
      connected the hooks of the cup to the hooks of the removable appliance. The mean
      treatment time was 24 +/- 9 months. Mean SNA and ANB were significantly increased
      by 3.1 degrees +/- 1.6 degrees and 3.5 degrees +/- 1.7 degrees, respectively
      (p<0.001). The level of significance was set at P<0.05. The increase of SNA angle
      and ANS-PNS distance (p<0.001) and the decrease of nasolabial angle (P<0.004)
      indicated that the reverse chin cup was effective in moving the maxilla in a
      forward position. Moreover, the smaller size of this appliance makes it more
      favorable for patients.

PMID- 20687314
TI  - The miracle of "forced eruption".

PMID- 20687315
TI  - Team tips.

PMID- 20687316
TI  - Recent events illustrate the importance of organized medicine.

PMID- 20687317
TI  - Dependent coverage under federal health reform--more than what meets the eye.

PMID- 20687318
TI  - The flawed SGR formula--why are we still fighting about this?

PMID- 20687319
TI  - Curricula of medical schools must keep up with changes in health care.

PMID- 20687320
TI  - Protecting the right to express an opinion without fear of a libel suit.

PMID- 20687321
TI  - The perils of being a scientist.

PMID- 20687322
TI  - Biological factors and brain imaging.

PMID- 20687323
TI  - Accelerated mental decline after head injury.

PMID- 20687324
TI  - Fact or fraud?

PMID- 20687325
TI  - Jackson civil litigation costs review--impact on the personal injury market.

PMID- 20687326
TI  - The Kansas City, Missouri, ground-level ozone (GLO) project: a community-based
      air pollution field experiment.
AB  - Tropospheric ozone concentrations for Kansas City are well known on a regional
      scale. The Kansas City, Missouri, ground-level ozone (GLO) project measured
      outdoor ozone concentrations using passive sensing devices (PSDs) on a
      neighborhood scale. Highly resolved exposure maps were made based on the detailed
      air quality observations collected during the seven week sampling study during
      the summer of 2005. Data analysis demonstated that ozone concentration levels
      were higher in urban core neighborhoods compared to the surrounding surbuban
      areas. The results have negative implications for the respiratory health of
      residents of urban Kansas City.

PMID- 20687327
TI  - Reduced PM2.5 in Trujillo, Peru, on El Dia Sin Autos ("The Day Without Cars").
AB  - Street-level and rooftop (three-story building) concentrations of particulate
      matter < or = 2.5 microm in diameter (PM2.5) were measured in downtown Trujillo,
      Peru, in July and August 2003 to determine the PM2.5 concentration reduction on
      days with normal traffic conditions (32 days) versus a day when motor vehicles
      were temporarily banned from the downtown district (8:00 a.m. to 6:00 p.m., July
      15) known as El Dia Sin Autos ("The Day Without Cars"). The mean 8:00 a.m. to
      6:00 p.m. street-level PM2.5 concentration during the motor vehicle ban (21.4
      microg/m3; one day) was 49% lower than when vehicles were not impeded (42.2 +/-
      7.8 microg/m3--mean +/- 1 standard deviation; 20 days). The rooftop monitoring
      station indicated a 20% decrease in PM2.5 concentrations (24.8 +/- 2.6 microg/m3
      vs. 19.9 +/- 6.0 microg/m3) when motor vehicles were not present within historic
      downtown Trujillo. Temperature, relative humidity, and wind speed during the
      motor vehicle ban and during normal traffic were not significantly different (p >
      .05).

PMID- 20687328
TI  - Does cosmic weather affect infant mortality rate?
AB  - In this article, the author proposes to consider a link between infant mortality
      rate (IMR) and galactic cosmic radiation (CR) density. The periodical increase in
      solar activity increases the effect of the magnetic field of the sun, and
      therefore weakens galactic cosmic rays hitting the Earth's surface. As a result,
      embryos in their early stages of development may be less exposed to high-energy
      ionizing cosmic rays when the solar activity peaks. In the study discussed here,
      cosmic ray density data were correlated with the U.S. infant mortality rate in
      the following year. Statistical analysis shows that in the past 30 years, Pearson
      correlation between the change in galactic CR flux and IMR decrease in the
      following year was -0.36 (p < .05).

PMID- 20687329
TI  - Communication as an essential component of environmental health science.

PMID- 20687330
TI  - State legislatures prepare to address environmental public health issues in 2010
      legislative sessions.

PMID- 20687331
TI  - The quest to be relevant and the results of our efforts. Part 1--The background
      to why relevance is the central driver to the NEHA story.

PMID- 20687332
TI  - [OSMAC (one strain many compounds) approach in the research of microbial
      metabolites--a review].
AB  - Microbial secondary metabolites have a wide range of biological activities due to
      their structural diversity and have been proved a major source for drug lead
      compounds. However,the traditional method of a single culture restricts the
      metabolic pathways of microorganisms and as a result many metabolites cannot be
      formed. Recently,it has attracted much attention to use various techniques to
      activate those metabolic pathways restricted by the traditional method to get
      metabolic products with rich variety of structures. "One strain many compounds"
      (OSMAC) is a simple and effective approach for activating metabolic pathways and
      has been successfully applied. This review summarizes the common strategies of
      the OSMAC approach (altering cultivation parameters, co-cultivation, addition of
      enzyme inhibitors, etc) and the recent advances of OSMAC combined with genomics
      scanning. This review also introduces the research of our studies using the OSMAC
      approach on a fungus Spicaria elegans KLA03 which yielded a series of
      cytochalasins.

PMID- 20687333
TI  - [Biodiversity of phosphate-dissolving and plant growth--promoting endophytic
      bacteria of two crops].
AB  - OBJECTIVE: We isolated and characterized phosphate-dissolving endophytic bacteria
      from two commonly cultivated crops. METHODS: Phosphate-dissolving endophytic
      bacteria were isolated by plating and screening from interior tissues of rape and
      maize plants on NBRIP medium with tricalcium phosphate as sole phosphate source.
      Bacteria were characterized regarding characteristics that may be relevant for a
      beneficial plant-microbe interaction-indoleacetic acid, siderophore and 1
      aminocyclopropane-1-carboxylic acid deaminase production,and further classified
      by restriction analysis of 16S rDNA. Eleven typical strains were identified by
      16S rDNA sequence analysis. RESULTS: Thirty-two phosphate-dissolving endophytic
      bacteria were isolated from maize and rape plants and classified by restriction
      analysis of 16S rDNA in 8 different taxonomic groups at the similarity level of
      76%. All the isolates could release phosphate from tricalcium phosphate and
      decrease the pH of the medium. The maximum phosphate content (537.6 mg/L) in the
      solution was obtained with strain M1L5. Thirteen isolates isolated from rape
      produced indoleacetic acid and siderophore, 68.4% and 63.2% of the strains
      isolated from maize produced indoleacetic acid and siderophore,respectively.
      63.2% of the strains isolated from maize were able to grow on 1-aminocyclopropane
      1-carboxylic acid as the sole nitrogen source. The eleven strains belonged to
      five different genera including Pantoea, Pseudomonas, Burkholderia, Acinetobacter
      and Ralstonia. CONCLUSIONS: Phosphate-dissolving endophytic bacteria isolated
      from rape and maize plants have abundant characteristics relative to promoting
      plant growth and genetic diversity.

PMID- 20687334
TI  - [Diffusible signal factor production and virulence expression in deltarpfFxoo,
      deltarpfCxoo and deltarpfGxoo, the gene deletion mutants of DSF/Rpf signaling
      proteins of Xanthomonas oryzae pv. oryzae].
AB  - OBJECTIVE: To better elucidate the functions of RpfFxoo, RpfCxoo and RpfGxoo, 3
      proteins of diffusible signal factor (DSF)-dependent cell-cell signaling system
      in regulation of virulence expression of Xanthomonas oryzae pv. oryzae (Xoo).
      METHOD: Deltarpfxoo, the gene deletion mutants were generated from PXO99(A), the
      wild-type strain of Xoo via marker-exchanging and DSF biosynthesis and
      extracellular polysaccharide production and virulence to rice of the mutants were
      assayed. RESULT: rpfFxoo,rpfCxoo and rpfGxoo were cloned from the genomic DNA of
      PXO99(A) and the relative single or double mutants were constructed. Compared to
      PXO99(A), DSF production was deficient in deltarpfFxoo, deltarpfFCxoo and
      deltarpfFGxoo, while DSF was overproduced in deltarpfCxoo and reduced in
      deltarpfGxoo. DSF production of deltarpfFxcc, deltarpfCxcc and deltarpfGxcc, the
      mutants of X. campestris pv. campestris can be restored as XC1, the wild-type
      strain by in trans complementation of rpfFxoo, rpfCxoo and rpfGxoo. All the
      mutants except deltarpfFxoo were remarkably deficient in production All the
      mutants significantly exhibited the reduced bacterial virulence to rice. of
      extracellular polysaccharide. CONCLUSION: DSF signaling proteins RpfFxoo, RpfCxoo
      and RpfGxoo might function in regulation of DSF biogenesis and EPS production and
      bacterial virulence.

PMID- 20687335
TI  - [Cloning and expression of the osmotic tolerance gene Bbmpd of Beauveria
      bassiana].
AB  - OBJECTIVE: We isolate the gene involved in osmotolerance of Beauveria bassiana
      for investigation the adaptation mechanism of the fungus to adversity. METHODS: T
      DNA tagging and genomic DNA walking were carried out by using Y-shaped adaptor
      dependent extension (YADE) method. RT-PCR was used to analyze the transcription
      profile of Bbmpd. RESULTS: A gene (Bbmpd) encoding mannitol 1-phosphate
      dehydrogenase in B. bassiana was identified. The transcription of Bbmpd was
      induced by osmostress (0.8 mol/L NaCl) in wild type strain, while significantly
      decreased in Bbhog1 mutant, indicating that the transcription of Bbmpd was
      regulated by Hog1 pathway in B. bassiana. Bbmpd-disrupted mutants showed
      sensitive to osmostress on Czapek's medium containing 0.8 mol/L NaC1. However,
      the growth and sporulation of the Bbmpd-disrupted mutants in vitro were not
      significantly different from that of wild type strain. CONCLUSION: Mannitol 1
      phosphate dehydrogenase gene was isolated by T-DNA tagging,and was found to be
      involved in the osmostress of B. bassiana. The transcription of Bbmpd was induced
      by osmostress and regulated by Hog1 pathway.

PMID- 20687336
TI  - [Removal of microcystin-LR by lactic acid bacteria].
AB  - OBJECTIVE: The performance of Lactobacillus salivarius BBE09-18, L. fermentum
      BBE09-29 and L. casei Zhang to remove the cyanobacterial toxin microcystin-LR (
      MC-LR) were determined in this study, and the key factors related to the removal
      efficiency were investigated to analyze the specific mechanism and provide a
      novel way to deal with the MC-LR contaminated foods. METHODS: Investigate the
      microcystin-removing capability of cells in different physiological status, e. g.
      viable and nonviable cells, and compare their removing effects with different
      biomass, toxin concentration and glucose supplement. RESULTS: Among these
      strains, L. casei Zhang removed the microcystin-LR most effectively. After a
      removal treatment with L. casei Zhang for 24 h (10(9)) CFU/mL, pH7, 37 degrees
      C), the MC-LR concentration deduced from 150 microg/L to 85. 5 microg/L. Results
      also showed that the viable cells were more effective for MC-LR removal than the
      nonviable ones. Moreover, the removal performance can be improved significantly
      when glucose was added, and the maximum removal of 92% was observed for L. casei
      Zhang ( toxin initial concentration 1800 microg/L,10(10) CFU/mL, pH 7.0, 37
      degrees C, 24h) with 5% glucose supplement. CONCLUSION: All of the three LAB used
      in this study can remove MC-LR. It can be confirmed that some factors, such as
      biomass, toxin concentration and energy supplement of cells play important roles
      on the removal efficiency. These results suggest further that the mechanism of MC
      LR removal in LAB may be related to their metabolic activity.

PMID- 20687337
TI  - [Cloning of Enterobacter aerogenes fh1A gene and overexpression of hydrogen
      production].
AB  - OBJECTIVE: We amplified and overexpressed the FHL activator (fh1A) in E.
      aerogenes ATCC13408 to enhance hydrogen production. METHODS: By using universal
      primers and genome walking, we cloned the full open reading frame (ORF) of fh1A
      gene. We inserted it into the glutathion S-transferase (GST) fusion expression
      vector pGEX4T-2-Cat, and transformed the recombinant plasmid into E. aerogenes
      ATCC13408 via electroporation for expression. Then we measured the hydrogen
      production of the recombinant strain in a batch culture. RESULTS: We found that
      the ORF of fh1A was 2073 base pair in length, potential to encode a 690 amino
      acid peptide (GenBank accession GU188474). The Fh1A protein from E. aerogenes
      ATCC13408 shared high amino acid identities with those from other bacterial
      species. By using SDS-PAGE and Western blot analysis, we confirmed that the fh1A
      gene had successfully expressed in the strain. The hydrogen yield of the
      recombinant strain was increased from 1.23 to 1.48 mol H2/mol glucose. [
      Conclusion ] Enhancement of hydrogen productivity was attained under anaerobic
      conditions with the recombinant strain.

PMID- 20687338
TI  - [The interaction between chromosome-encoded toxin Slr0664 and antitoxin Slr1114
      of cyanobacteria Synechocystis sp. PCC6803].
AB  - OBJECTIVE: We identified the interaction between toxin Slr0664 and antitoxin
      Slr1114, encoded by ssr114/ slr0664 system in the chromosome of cyanobacteria
      Synechocystis sp. PCC6803. METHODS: We constructed a recombinant plasmid in which
      only H6-Ssr1114 was induced to express, and another plasmid in which both H6
      Ssr1114 and Slr0664 was co-expressed in E. coli B121(DE3). After induction, we
      used affinity capture technique to purify H,-Ssr1114 and copurified H6-Ssr1114
      and Slr0664 under different conditions. We confirmed the co-purified H,-Ssrl 114
      and S1l0664 by using mass spectrographic analysis. RESULTS: When induced to
      express, Slr0664 showed cell toxicity leading to cell growth suppression or
      death. However, cells could grow normally if both H6-Ssr1114 and Slr0664 were
      induced to co-express. We could purify both H6-Ssr1114 and Slr0664 by His-Bind
      under native conditions, but only H4-Ssr1114 could be purified under denature
      conditions. The results of mass spectrometric analysis showed that the copurified
      proteins were H,-Ssrlll4 and Slr0664. CONCLUSION: The antitoxin Slr1114 and toxin
      Slr0664 in ssr1114/slr0664 TA system was interacted with each other.

PMID- 20687339
TI  - [Heterogeneous expression of chitinase gene from Bcillus licheniformis MY75 and
      the characterization of expressed ChiMY].
AB  - OBJECTIVE: To heterogeneously express the chitinase gene of Bacillus
      licheniformis strain MY75 in E. coli, and to characterize the recombinant
      chitinase ChiMY. METHODS: The extracelluar crude protein from B. licheniformis
      MY75 was analyzed by zymogram analysis. The partial amino acid sequence of the
      protein owned chitinase activity was given by time-of-flight mass spectrometry
      (TOF-MS). Then the corresponding chitinase gene chiMY was cloned and
      heterogeneously expressed in E. coli. The optimum temperature and pH of the
      ChiMY, and the effect of various metal ions on chitinase activity were studied.
      The antifungal activity and the synergistic effect on insecticidal activity were
      demonstrated by bioassays. RESULTS: A 55 kDa extracelluar protein produced by B.
      licheniformis MY75 exhibited chitinase activity in zymogram analysis. The chiMY
      gene was 1797 bp long and encoded a 599 amino acid protein. The molecular weight
      of the recombinant protein ChiMY over-expressed in E. coli was 67 kDa. The amino
      acid sequence of the 55 kDa extracelluar protein was proved identical to the 67
      kDa ChiMY by the TOF-MS. The optimum temperature and pH were 50 degrees C and
      7.0, respectively. The enzyme activity was improved by Li+, Na+ and Mg2+ and
      inhibited by Mn2+, Cr3+, Zn2+, and Ag+. Cu2+ and Fe3+ can inactivate the enzyme.
      The bioassays demonstrated the heterogeneously expressed ChiMY could inhibit the
      sporangia germination of G. saubinetii and A. niger, and reduce the LC50 (50%
      lethal concentration) of the crystal protein of Bacillus thuringiensis against S.
      exigua by approximately 27%. CONCLUSIONS: The B. licheniformis MY75 could produce
      a 55 kDa chitinase. The corresponding chitinase gene was over-expressed in E.
      coli. The molecular weight of heterogeneously expressed ChiMY showed significant
      different to the wild-type chitinase protein. This implicated the the protein
      processing of chitinase in the B. licheniformis MY75. The ChiMY also owned the
      antifungal activity and could improve the insecticidal activity of the Bacillus
      thuringiensis crystal protein against S. exigua. This is the first report about
      the chitinase from B. licheniformis in China.

PMID- 20687340
TI  - [Cloning and expression of non-position-specific lipase gene from Proteus
      vulgaris].
AB  - OBJECTIVE: To produce Proteus vulgaris lipase (PVL) in large quantities, we
      cloned and expressed the lipase gene in Escherichia coli. METHODS: We cloned PVL
      gene by PCR method and then inserted the open reading frame of PVL gene into pET
      DsbA and pMBP-P vectors. PVL gene was expressed in E. coli with the introduction
      of isopropyl beta-D-1-thiogalactopyranoside (IPTG). We also studied the optimal
      culture conditions, including the concentrations of glucose, IPTG and ampicillin,
      induction temperature, and pH value of the medium. The characteristics of
      recombinant lipase were examined after affinitive purification by His-chelating
      affinity chromatography. RESULTS: The open reading frame of PVL gene consisted of
      864 base pairs, encoding a protein of 287 amino acids. The sequence was deposited
      to GenBank with the accession number FJ643627. The gene was expressed in E. coli
      and active lipase was obtained from E. coli BL21 cells by the induction of IPTG,
      and the lipase production reached 192. 2 U/mL in BL21 [pET-PVL] after culture for
      15 h at 15 degrees C. The maximum production was obtained by culturing BL21 cells
      in LB medium (pH 8.5) with 15 mg/mL glucose and 200 mg/L ampicillin, as well as
      adding 100 mg/L IPTG at OD600 of 1.2. A single protein band of 31 kDa was
      displayed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE)
      after affinitive purification. The properties of lipase expressed in E. coli were
      similar to the native one, which could hydrolyze all three esters of
      triglyceride. CONCLUSION: We have succeeded in over-expressing the lipase gene
      from P. vulgaris in E. coli, and this research has laid a foundation for
      improvement and industrial application of this lipase.

PMID- 20687341
TI  - [Construction of integrative vector for xylulokinase gene and its overexpression
      in Saccharomyces cerevisiae].
AB  - OBJECTIVE: An integrative vector of Saccharomyces cerevisiae for xylulokinase
      gene expression was constructed to overexpress xylulokinase activity. METHODS: On
      the basis of plasmid p406ADH1, 4 components were integrated, which were KanR gene
      as G418 resistant marker, ADH1 terminator fragment, xylulokinase gene from
      Saccharomyces cerevisiae W5 and 18S rDNA sequence for homologous recombination.
      After enzyme digestion and ligation, high copy recombinant expression vector pCXS
      RKTr was constructed. pCXS-RKTr was linearized and transferred into Saccharomyces
      cerevisiae W5 , then xylulokinase activity was detected to determine the
      expression of pCXS-RKTr. RESULTS: Xylulokinase gene located on pCXS-RKTr was
      highly expressed in W5. The xylulokinase activity was 2. 87 times of the original
      strain. CONCLUSION: An integrative vector of industry strain Saccharomyces
      cerevisiae is successfully constructed and xylulokinase gene of Saccharomyces
      cerevisiae itself was over expressed by this vector. This intergrative vector can
      efficiently raise the xylulokinase activity of Saccharomyces cerevisiae. This
      system laid a foundation for the construction of gene engineering Saccharomyces
      cerevisiae strain which can ferment xylose to ethanol.

PMID- 20687342
TI  - [Effect of Mortierlla isabellina delta5-desaturases gene on arachidonic acid
      synthesis].
AB  - OBJECTIVE: To study the relation between mRNA expression of delta5-desaturase
      gene and arachidonic acid production. METHODS: Using fluorescence quantitative
      PCR, we determined the mRNA expression levels of delta5-desaturase gene of five
      Mortierlla isabellina strains cultured for the same time and strain YZ-124
      cultured for different time. Simultaneously, we measured the contents of
      arachidonic acid by gas chromatography. RESULTS: The results showed that delta5
      desaturase gene mRNA expression level of distinct strains was different.
      Expression level of the original strain As3. 3410 was the lowest, whereas that of
      the mutant strain YZ-124 was the highest. The mRNA expression of delta5
      desaturases gene decreased gradually with fermentation time. CONCLUSION:
      According to arachidonic acid yield, mRNA expression quantity of delta5
      desaturase gene presented a positive correlation with arachidonic acid content in
      cultured oil.

PMID- 20687343
TI  - [Contributions of putative lipoate-protein ligase to the virulence of
      Streptococcus pneumoniae].
AB  - OBJECTIVE: To investigate the effect of putative lipoate-protein ligase (LPL) on
      the virulence of Streptococcus pneumoniae. METHODS: lpl gene deficient strain was
      constructed by LFH-PCR and identified by PCR and sequencing. The cell adherence
      assay and mice challenge assay were used to observe the differences between wild
      strain and the mutant in the pathopoiesis of Streptococcus pneumoniae. RESULTS:
      Mice virulence experiments showed that the median lethal time of wide type and
      the lpl mutant are both 12 h, no statistics difference. The ability of adherence
      of the mutant was greater than the wild strain (P < 0.01); The capsule stain in
      vivo showed that the wild strain and the mutant both had the capsule. CONCLUSION:
      lpl gene inhibits the adherence to host, but no affect on the ability to
      infection mice by

PMID- 20687344
TI  - [Effect of lignite humic acid on soil ammonia oxidizing archaea community].
AB  - OBJECTIVE: To illuminate the impact of humic acid (HA) on soil ammonia oxidizing
      archaea and then reveal the effect of HA on soil nitrogen cycle. METHODS: Two
      humic acids (cHA and bHA) were added into the soil amended with urea. Community
      changes of ammonia oxidizing archaea (AOA) and total archaea were studied with
      terminal restricted fragment length polymorphism (T-RFLP) and real time PCR in
      the microcosm experiment. RESULTS: We found that the AOA population size
      increased significantly and AOA community changed greatly in the urea only
      treatment. However, HA could inhibit the increase of AOA population, moreover, HA
      could buffer the change in AOA community showed by canonical correspondence
      analysis (CCA) result. On the other hand, the total archaeal population decreased
      significantly in the urea only treatment, but stabilized in the urea with HA
      treatments, which indicated HA could eliminate the toxicity of urea to total
      archaea. CCA results showed that incubation time was the most important factor
      for the total archaeal community, and partial CCA (pCCA, when time as a
      covariable) result demonstrated that cHA was the most important environmental
      variable for total archaeal community. CONCLUSION: These results showed that HA
      diminished ammonia loss by inhibiting the increase of AOA competing with plant
      for ammonia, thus HA can increase the urea efficiency.

PMID- 20687345
TI  - [Antimicrobial susceptibility and related genes of Salmonella serovars from
      retail food in Shaanxi province].
AB  - OBJECTIVE: Salmonella isolates from retail food were examined for antimicrobial
      susceptibility and further characterized to better understand the development and
      dissemination of antimicrobial resistance among foodborne Salmonella in China.
      METHODS: Antimicrobial susceptibility of 359 Salmonella isolates was determined
      by using agar dilution methods recommended by the Clinical and Laboratory
      Standards Institute. Antimicrobial resistance integrons and resistance genes were
      identified using PCR. Mutations in gyrase and Topoisomerase genes related to
      fluoroquinolones resistance were also determined using PCR and gene sequencing
      analysis. RESULTS: Among the 359 Salmonellae isolates, 67% were resistant to
      Sulfamethoxazole, followed by resistant to trimethoprim/Sulfamethoxazole (58%),
      tetracycline (56%), kanamycin (37%), nalidixic acid (35%), ampicillin (33%),
      amoxicillin/clavulanic acid (32%), streptomycin (29%), chloramphenicol and
      gentamicin (26%), ciprofloxacin (21%), ceftriaxone (16%), cefoxitin (9%) and
      cefoperazone (8%). Among the 284 resistant isolates, 79% were resistant to at
      least one antimicrobial, 25.9% to 10 or more than 10 antimicrobials, and 2.5% to
      14 antibiotic agents. Integrons were detected in some of sulfamethoxazole
      ressitant Salmonella, and the most common integron was 1.4 kb, Antimicrobial
      resistance genes carried by integrons included aadA1, aadA2, aadA5, tetR,
      blaPSE1, blaDHA1, blaVEB-1, dhfr I, dhfr V, dhfrVl and dhfr17. The blaTEM gene
      was also detected in 51.6% of 62 ceftriaxone and/or cefoperazone resistant
      isolates, and blacMY-2 was detected in 56.5% of the isolates. 13.6% of the
      Salmonella isolates carried Salmonella Gene Island. Sixty-eight point mutations
      were detected in gyrA, parC and parE of 35 fluoroquinolone-resistant Salmonella
      isolates. The common mutations in gyrA gene were Ser83Phe, Ser83Tyr, Asp87Gly and
      Asp87Asn, whereas ser80Arg was detected in parC. Mutations including Lys441 Ile,
      Lys428Gln, Asp494Asn, Lys428Gln and Gly442Ser were detected in parE, which was
      first reported in Salmonella. CONCLUSION: Antimicrobial resistance of Salmonella
      recovered from food in Shaanxi province was common. Several genetic elements
      including integron, Salmonella Gene Island, beta-lactamase genes and mutations in
      gyrase and topoisomerase genes played an important role in antimicrobial
      resistance of Salmonella.

PMID- 20687346
TI  - [Isolation of a bacterial strain capable of bezafibrate-degrading and
      biodegradation characteristics].
AB  - OBJECTIVE: Bezafibrate is one of the most frequently detected pharmaceuticals at
      relatively high concentration in surface water and even in drinking water.
      Biodegradation is an important way to solve the problem. This study aimed to
      isolate, identify and characterize a bezafibrate-degrading bacterium. METHODS:
      Strain B31 capable of degrading bezafibrate by cometabolism was isolated from
      activated sludge of sewage treatment plant in Shanghai, China, and identified
      based on its morphology, physiology and phylogenetic analysis of 16S rRNA
      sequence. To evaluate the ability of degradation, the concentration of
      bezafibrate was detected by high performance liquid chromatography. RESULTS:
      Strain B31 was identified to be closely related to Pseudomonas putida. The
      optimum condition of degrading bezafibrate was at 30 degrees C, pH 7. After 5
      days, Strain B31 could degrade 30 mg/L bezafibrate by 48% in liquid mineral salt
      medium with 1% methanol as primary substrate. And the rate of degradation could
      enhance to 61%, 72.6%, 76.67%, when 5 g/L glucose, peptone and yeast extract as
      primary substrate, respectively. CONCLUSION: The strain has the potential for
      bezafibrate biodegradation.

PMID- 20687347
TI  - [Isolation, identification and characterization of a high-efficient heterotrophic
      nitrifier].
AB  - OBJECTIVE: In order to improve the rate of the heterotrophic nitrification, we
      screened and identified a high-efficient heterotrophic nitrifier, as well as
      studied its nitrification characteristics and nitrification conditions. METHODS:
      We obtained activated sludge samples from sewage and chemical fertilizer
      factories and farmland. We then utilized sodium citrate and ammonium chloride as
      carbon and nitrogen source. We used methods including domestication, gradient
      dilution of domestication liquid, isolation from streaking plate and color
      indicator as rapid nitrification detection. Finally a high-efficient
      heterotrophic nitrifier was obtained. We identified this strain according to its
      physiological, biochemical properties and the sequence analysis of 16S rDNA.
      After inoculating the strain into artificial ammonia-nitrogen wastewater, changes
      of nitrogen compounds were measured in order to understand the nitrification
      characteristics. Nitrification condition was also optimized by changing the
      carbon source, dissolved oxygen, C/N ratio, temperature and pH of the medium.
      RESULTS: The heterotrophic nitrifier was a gram-negative bacilli. It neither
      fermented glucose, nor produced indole. Oxidase and catalase tests were positive.
      It could produce alkali if organic salt was provided. The strain shared 99.7%
      sequence identity of its 16S rDNA with ES-SDK-3 of Alcaligenes sp. In the
      artificial wastewater with 182.30 mg/L ammonia nitrogen as initial concentration,
      the removal efficiency by the strain was 99. 8% after 30h cultivation. The
      average nitrogen removal rate was 9. 61 mg-N/L/h in its exponential phase. It
      produced almost no NO(2-)-N and NO(3-)-N in the entire nitrification process. The
      optimal carbon source is sodium citrate. Higher dissolved oxygen and C/N ratio
      favor its nitrification. When temperature is ranged from 30 degrees C to 35
      degrees C and pH is ranged from 5.0 to 9.0, it can completely remove ammonia
      nitrogen. CONCLUSIONS: The strain was identified as Alcaligenes genus, and named
      as Alcaligenes sp. HN-S. Our research confirmed that the Alcaligenes sp. HN-S had
      significant advantages over heterotrophic nitrifiers that were screened
      previously with aspect of ammonia nitrogen removal rate. The research of its
      nitrification condition definitely provided necessary theory support for a new
      biology process to remove nitrogen with high efficiency.

PMID- 20687348
TI  - [Construction of recombinant adenovirus expressing Ag85B of Mycobacterium bovis
      and its cellular immunoproperties in mice].
AB  - OBJECTIVE: We constructed recombinant adenovirus rAd-Ag85B expressing antigen 85B
      of Mycobacterium bovis and analyzed cellular immune responses after mice
      immunization. METHODS: We amplified the fbpB gene from genomic DNA of BCG by PCR
      and cloned into pMD18-T vector for sequence analysis. Then we constructed pDC516
      Ag85B and co-transfected with plasmid pBHGfrtdeltaE1, 3FLP into Ad293 cells by
      lipofectamine 2000. Then we identified the recombinant Ad-Ag85B virus by RT-PCR,
      Western blot assay and TEM observation after negative staining. BALB/c mice were
      subcutaneously immunized with the dose of 10(8) TCID50 rAd-Ag85B or rAd. Two
      weeks after immunization, CD69 expression, T lymphocyte proliferation and ELISPOT
      were detected in spleen cells of immunized mice. RESULTS: We obtained the correct
      recombinant adenovirus rAd-Ag85B expressed Ag85B antigen. The level of both
      splenic CD69+ CD4+ T and CD69+ CD8+ T cells of rAd-Ag85B group were significantly
      higher than those of rAd control. The SI index of rAd-Ag85B was much higher than
      rAd. In ELISPOT assay more IFN-gamma specific secreting cell spots other than IL
      4 were detected in rAd-Ag85B group. CONCLUSION: The recombinant adenovirus rAd
      Ag85B can induce specific Th1 cell immune responses in mice.

PMID- 20687349
TI  - [Influence of native bacterial magnetic particles on mouse immune response].
AB  - OBJECTIVE: To study the influence of native bacterial magnetic particles on mouse
      immune response. METHODS: Ovalbumin was used as an antigen, mixed with complete
      Freund's adjuvant, bacterial magnetic particles (BMP) and phosphate buffer
      solution, to immunize BALB/C mouse. After 14 days later, we detected the titers
      of the antiovalbumin (IgG) and subtype (IgG1, IgG2a) , the proliferation ability
      of T lymphocyte, and the expression of IL-2, IL4, IL-10 and IFN-gamma. RESULTS:
      Compared to the negative control group, the BMP group had the similar level in
      the titer of specific antibody, the proliferation ability of T lymphocyte and the
      expression of cytokines (IL-2, IL-4, IL-10 and IFN-gamma). CONCLUSION: Native
      BMPs has no significantly influence on mouse immune response.

PMID- 20687350
TI  - [Construction of in-frame deletion streptococcal hemoprotein receptor gene mutant
      in Streptococcus equi subsp. zooepidemicus].
AB  - OBJECTIVE: To construct the in-frame deletion gene mutants in streptococcus equi
      subsp. zooepidemicusby (S. zooepidemicus) by pJR700 plasmid, a thermosensitive
      delivery vector system. METHOD: With PCR we amplified a 4017-bp DNA fragment of
      streptococcal hemoprotein receptor gene from chromatosome DNA. This DNA fragment
      was subcloned into the pJR700 plasmid to create pXL28. Using pXL28 as the
      template we got the DNA fragment deleted 1831 bp in streptococcal hemoprotein
      receptor gene by inverse PCR amplification and ligated the in-frame deletion DNA
      fragment by T4DNase to create pXL30. Then pXL30 was transformed into S.
      Zooepidemicus by electroperation. The kanamycin( kan)-resistant clones were
      selected at 37 degrees C in the presence of kan for three rounds. To induce
      excision of the plasmid vector sequence, the culture was shifted to 30 degrees C
      and grown without antibiotics for four rounds. Colonies with kan sensitivity,
      which indicated that the plasmid had been excised, were selected by plating on
      THY agar at 37 degrees C. S. Zooepidemicus mutants were identified through PCR
      with primers homologous to the flanking regions and the streptonigrin sensitive
      test. RESULT: The in-frame deletion streptococcal hemoprotein receptor mutants
      were successfully built in S. Zooepidemicus. CONCLUSION: The thermosensitive
      delivery vector system of pJR700 could be utilized to construct the in-frame
      deletion gene mutant strains of S. Zooepidemicus.

PMID- 20687351
TI  - [Comparison of midgut bacterial community between Bt-resistant and sensitive
      Helicoverpa armigera].
AB  - OBJECTIVE: To investigate the midgut bacterial community of sensitive and
      resistant Helicoverpa armigera for the emergence of resistance to Bacillus
      thuringiensis. METHODS: Two culture-independent techniques (16S rDNA library and
      DGGE) were introduced. The genomic DNA of midgut bacteria was extracted. The full
      length gene of 16S rDNA was amplified by PCR and then cloned. The 16S rDNA
      library was analyzed with Alu I and Sac I. The V3 region of 16S rDNA was
      amplified by PCR. The intrapopulation variation and variation between resistant
      and sensitive Helicoverpa armigera were assayed by DGGE. RESULTS: Analysis of 16S
      rDNA library showed similar patterns of midgut bacterial structure and diversity
      in terms of the dominant bacteria, but the inferior bacteria were significant
      different. The resistant population harbored abundant phylotypes belonging to
      uncultured bacterium (56.4%), Enterococcus gallinarum (17.0%) and Enterococcus
      casseliflavus (17.0%). For the sensitive population, the dominant bacteria were
      uncultured bacterium (60.2%), Enterococcus casseliflavus (14.7%) and Enterococcus
      gallinarum (19.3%). The divergence of midgut bacteria community between resistant
      and sensitive populations detected by 16S rDNA library analysis was verified by
      PCR with specific primers, and the result showed that all those inferior bacteria
      presented in both varieties. DGGE profile revealed that the similarity of the two
      varieties was 92.3%. CONCLUSION: The midgut bacterial community of resistant and
      sensitive H. armigera was similar, which had no direct effect on Bt-resistance of
      H. armigera.

PMID- 20687352
TI  - [The diagnostics of dementia using MR proton spectroscopy].
AB  - OBJECTIVE: The objective of this study was to find the determinants of
      degenerative processes in the ageing brain, with the particular emphasis on
      Alzheimer-type dementia, using MR proton spectroscopy (1HMRS). MATERIAL/METHODS:
      The sample consisted of 155 persons investigated who were divided into four
      groups: the control group Y (44 persons, the mean age of 64.6 years) and 3 groups
      of patients diagnosed with dementia. Group A (47 persons, the mean age of 65.6
      years) with Alzheimer-type dementia, group N (46 patients, the mean age of 64.8
      years) with vascular dementia and Group M (15 patients, the mean age of 65.3
      years) with mixed type dementia. Imaging (MRI) and spectroscopic (1HMRS)
      examinations were performed using MR Signa Horizon 1.5 T system (GEMS) with the
      use of a standard volume head coil. A single voxel spectroscopy (SVS) was used,
      with VOI located in the following areas: frontal, paraventricular,
      parietooccipital and the hippocampus). Qualitative analysis of the spectrum was
      made (the profile analysis) as well as quantitative analysis and the relative
      concentration ratios (RCR) were calculated for selected metabolites (NAA, Cho,
      ml, Cr); the Cr concentration was assumed as the internal standard. Detailed
      analysis of each group was made followed by the comparison with Group Y. RESULTS:
      1HMRS spectra in the patients with Alzheimer-type dementia reveal characteristic
      changes: the increase in ml/Cr RCR and the decrease in NAA/Cr and NAA/ ml RCRs,
      which were statistically significant almost for all the locations. There is a
      clear change in the spectrum profile: the lowered NAA peak and elevated ml. In
      the RCRs of the patients with angiogenic dementia no characteristic changes were
      found either in the quantitative or qualitative spectrum analyses. On the other
      hand, the appearance of Lip and Lac peaks allows coming to the conclusion
      indicating the angiogenic character of dementia. the quantitative analysis.
      However, in the qualitative analysis in the patients in that group an elevated ml
      peak always occurred. The appearance of Lip and Lac peaks with elevated ml peak
      allows coming to the conclusion indicating the mixed character of dementia.
      CONCLUSIONS: On the base of the results obtainedit may be concluded that both the
      data of the analysis of the RCRs for selected metabolites (NAA, Cho, Cr, ml) and
      spectra allow the diagnosis of Alzheimer-type dementia.

PMID- 20687353
TI  - [Usefulness of proton MR spectroscopy for determining diagnosis and treatment
      outcome in unipolar depressive disorder].
AB  - PURPOSE: The aim of the study was to evaluate the usefulness of proton MR
      spectroscopy for determining the biochemical abnormalities in acute episode of
      depression and after regression of the disease in course of unipolar depressive
      disorder. MATERIAL AND METHODS: Forty one patients (age 18-55 years) with known
      unipolar depressive disorder (a Hamilton Depression Rating Scale of 16 or
      greater) were evaluated by the means of HMRS during acute episode of depression
      and after positive therapeutic response (at least 50% reduced Hamilton score for
      at least 4 consecutive weeks). All patients underwent single-volume 1H MRS
      (TR=1500 ms, TE=35 ms) using a 1.5T scanner. Four brain areas were analyzed: both
      frontal lobes and both hippocampi. RESULTS: In the acute fase of the disease
      patients had statistically significant increases in Cho/Cr levels in right
      hippocampus area and increases in ml/Cr levels in left frontal lobes relative to
      controls. After positive therapeutic response no significant abnormalities were
      found. CONCLUSION: These results suggest that abnormal increased brain
      metabolites should reverse after treatment. In the time of new imaging technics
      we hope that in the future 1H MRS may be helpful for determining the accuracy of
      the diagnosis and can improved prediction of therapeutic response in unipolar
      depression.

PMID- 20687354
TI  - [Myoinositol trends in HMRS brain spectrum of patients with hepatic
      encephalopathy].
AB  - Hepatic encephalopathy (HE) comprises a complex set of neuropsychiatric
      abnormalities upon primary hepatic dysfunction. Ammonia and other nitrogen-based
      compounds are thought to be essential etiological factors when dysmetabolized in
      the liver, they provoke highly undesirable neuroglial transmission in the central
      nervous system (CNS). Proton MR spectroscopy (HMRS) is a noninvasive in vivo
      method of analyzing the metabolic spectrum of neuronal tissue and its
      pathological changes even before overt clinical symptoms occur and can be seen in
      morphological MR examination. Myoinositol (ml) is one of the metabolites that can
      be identified with HMRS. It is considered a glial marker, directly involved in
      compensation processes to overcome toxic effects of hepatic metabolites which had
      crossed the brain-blood barrier. Thus, ml may be a crucial prognostic factor for
      patients with HE. The goal of the present paper was to selectively investigate ml
      trends upon the MR brain spectrum. 36 male participants were enrolled in the
      study: 20 patients (mean age 58.2 years) with clinical symptoms suggestive of HE
      in the course of either chronic viral hepatitis or post-viral liver cirrhosis,
      and 16 men (mean age 51.3 years) with normal liver function (control group).
      Brain MR examinations were performed in all participants, followed by HMRS in
      single voxel spectroscopy (SVS) technique from occipital gray matter of right
      (Voxel 1) and left (Voxel 2) cerebral hemispheres. MR data were acquired with a
      1.5 T GE Signa Excite scanner. ml peak height was normalized with respect to
      creatine. A statistically significant decrease in ml/Cr ratio has been
      appreciated in the MR spectra of HE patients. The mean ml/Cr ratio for HE
      patients was 0.75, and was 0.93 for the control group, and, for alpha = 0.05, the
      observed differences between ml/Cr ratio mean values appeared to be statistically
      significant.

PMID- 20687355
TI  - [Magnetic resonance spectroscopy (HMRS) in migraine].
AB  - INTRODUCTION: There are 4 million people suffering from migraine in Poland, which
      account; for 10% of national population. Pathomechanism of migraine is not fully
      understood. In the recent years multiple studies in migraine patients revealed
      occurrence of metabolic disorders in nervous system tissue. MATERIAL AND METHODS:
      In 30 subjects with migraine diagnosis magnetic resonance spectroscopy
      examination was performed. Relative concentration ratio (WSS) of metabolites
      level to creatinine (Cr) level was measured. The obtained values were compared to
      findings in control groups. RESULTS: Linear correlation between increase in both
      WSS Lac/Cr value in left temporal lobe and WSS ml/Cr value in right frontal lobe
      and a number of migraine attacks per year in migraine patients was observed. It
      also turned out that WSS ml/Cr vox3 value depends on a total number of migraine
      attacks in life. A lactic acid level in left temporal lobe normalizes along with
      the elongation of interattack interval. There is a statistically significant
      difference of WSS ml/Cr value measured in left temporal lobe and right frontal
      lobe between migraine patients and control group. There is a statistically
      significant difference of WSS Cho/Cr value measured in left temporal lobe and
      right frontal lobe between migraine subjects and control groups.

PMID- 20687356
TI  - [Optimalisation of lymph node assessment in patients undergoing therapy for
      lymphoma using a multi-row CT].
AB  - PURPOSE: Aim of the study was evaluation the accuracy of routinely performed
      helical computed tomography (CT) compared to modern multidetector row CT (MDCT)
      in staging and assessing response to treatment of patients with lymphoma,
      especially in cranio-caudal dimention. MATERIAL AND METHODS: 60 patients with
      known Hodgkin's disease localised in chest were evaluated by the means of two
      methods: axial reconstruction of 5-6 mm thick slices--typical set for helical CT
      and 2-mm thin slices with coronal and sagital reconstruction--typical set for
      MSCT. Each of 120 obtained examinations (240 images reconstructions) were
      evaluated by 2 blinded readers. RESULTS: Accuracy of measurements was greater at
      MSCT in all dimentions of evaluated lymph nodes (p<<0.0001). MSCT revealed in 15%
      of patients presence of lymph nodes enlarged only in craniocaudal length. Such
      nodes in conventional CT could be interpreted as "normal". Application of third
      dimention in lymph nodes assessment caused the change in clinical classification
      in 15% of patients in the study. Only in 40% of cases grade of response to
      treatment was the same in both CT ant MSCT techniques. CONCLUSIONS: MSCT improves
      the detection rate of enlarge lymph nodes, especially in cranio-caudal dimention
      and shoud replece conventional spiral CT in assessment patients with lymphoma. In
      the time of new imaging technics we propose to modify the clinical staging of
      limphoma.

PMID- 20687357
TI  - [The influence of MRI examination on prenatal guidance and therapeutic decisions
      in fetuses with central nervous system defects].
AB  - PURPOSE: The aim of this study was the evaluation of diagnostic and prognostic
      value of prenatal US and MRI in fetuses with central nervous system
      abnormalities, and of the influence of incorporating MRI to diagnostic algorithm
      on the therapeutic decisions. MATERIALS AND METHODS: 123 pregnant women (16-40
      weeks' gestation) underwent MRI due to abnormal appearance of fetal central
      nervous system in US (using Voluson-Kretz 730PRO). MRI has been performed on a
      1.5-T Excite (GE), using a phased-array body coil, with T2-weighted sequences
      (SSFSET2) and orthogonal scans. The MRI findings have been compared to those from
      prenatal US. The influence of MRI examination in prenatal diagnostic on decisions
      concerning termination of pregnancy, method of delivery and neurosurgical
      intervention after birth was assessed. RESULTS: Among 123 fetuses with central
      nervous system abnormalities, 11 neonates died after birth (in 6 cases pathologic
      examination was performed), in 67 cases the MR findings were correlated with the
      results of the neonatal evaluation, all other cases have not been verified.
      Almost in 70% of the cases, MRI findings complemented the US diagnosis, in 22
      cases changed it with respect to central nervous system defects, and in 18 cases-
      with respect to other system/organ abnormalities. In a few cases US failed to
      provide a correct diagnosis. In 3 cases, the MRI findings have not been confirmed
      with postnatal evaluation. CONCLUSIONS: Prenatal MRI in congenital central
      nervous system defects allows to obtain much more important therapeutic data and
      complement or correct the fetal sonographic diagnosis. Prenatal MRI allows to
      plan gynaecological, neonatal, neurosurgical treatment, and to predict
      neurological defects. It also improves prenatal guidance.

PMID- 20687358
TI  - [Assessment of degree and extent of resorption of incisor roots adjacent to
      impacted maxillary canines].
AB  - The object of the study was to assess the degree and extent of root resorption of
      incisors adjacent to impacted maxillary canines on the basis of CT examination,
      as well as presenting the effect of patient's age and localisation of the
      impacted canines upon the resorption process. MATERIAL AND METHOD: The study
      comprised 65 patients with suspected impaction of permanent maxillary canine. In
      all of the subjects pantomographic x-rays were performed. 44 patients aged 13-31
      (average 17.1 +/- 4.5) were found to present with an overlap of the crown of
      impacted canine over the incisor roots, in which case a CT scan was performed.
      The patients under study were divided into three smaller groups according to age:
      group I (13-15 years of age) comprising 18 persons (40.9%) with 23 impacted
      canines (42.6%); group II (16-18 years of age) with 14 persons (31.8%) and 18
      impacted canines (33.3%), and group III (19-31 years of age): 12 persons (27.3%)
      and 13 impacted canines (24.1%). The CT scans (including multiplanar and 3D
      reconstructions) were used to localise the impacted canines as buccal, palatal
      and horizontal. Also, the condition of the roots of lateral and/or central
      incisors was assessed. Moreover, the effect of impacted canine position and of
      the patient's age on occurrence and extent of incisor root resorption was
      analysed. RESULTS: Of the total of 54 impacted permanent maxillary canines, 41
      (75.9%) were positioned palatally, 10 (18.5%) buccaly, and 3 (5.6%) horizontally.
      There were 31 cases (64.6%) of lateral incisor root resorption, of which in 18
      (58.1%) resorption was deep, and in 13 (41.9%) it was light. The most damage
      (86.9) was found in the youngest group. There were also 8 cases (44.4%) of
      central incisor root resorption found primarily in the second age group.
      Statistically significant association between the position of the impacted
      CONCLUSIONS: A CT scan allows assessment of degree and extent of the resorption
      of lateral incisor roots adjacent to impacted maxillary canines. Age of patients
      is a significant factor which has an effect on occurrence of damage to incisor
      roots. Also the position of impacted canines has an effect on the process of
      resorption of incisor roots. Computed tomography still remains the method of
      choice in assessment of root resorption in teeth adjacent to impacted teeth.

PMID- 20687359
TI  - [Baloon dilatation of benign ureteroileal anastomotic strictures].
AB  - The study is presenting own experience with the use of percutaneous balloon
      angioplasty in the patients with the strictures of ureteroenteric anastomoses. A
      study group consisted of 11 patients with urinary bladder cancer in whom
      ureteroenteric anastomosis was performed. All patients developed in the
      postoperative period ureter strictures or the stenosis at the junction point of
      ureteroenterostomy resulting in retention of urea in the ureter and pyelocalyceal
      system requiring percutaneous nephrostomy. High-pressure balloon catheter
      inserted through the nephrostomy was placed centrally in the point of stenosis.
      The catheter was insufflated with physiological saline solution and contrast
      agent until ballon waisting disappeared. Subsequently temporary double-J catheter
      with diameter of 9 F or 12F was inserted and remained in place for the period of
      1-6 months. All patients were followed-up for 2 years, and underwent control USG
      and CT examinations. Fourteen urethral dilatations of bilateral strictures were
      performed in 3 patients and in 9 patients with unilateral strictures. In 10 (71%)
      cases the symptoms of stenosis disappeared for the period of 1 year. Procedure of
      ballon dilatation follow by introduction of the double-J catheter should be
      method of first choice in all cases of benign ureteroileal anastomotic
      strictures.

PMID- 20687360
TI  - [Anatomic variations of the septation within the sphenoid sinus on CT scan images
      -an initial report].
AB  - AIM: The aim of this study was to assess the septation of the sphenoid sinuses
      and relationship between the number and position of septa in the adult Polish
      subpopulation. METHODS: A retrospective study of the CT examination of the
      paranasal sinuses 207 patients (101 male, 106 female) were performed using spiral
      multirow CT scanner (Siemens Somatom Sensation 10) with the following parameters:
      the extent fully covering all paranasal sinuses, detector configuration 10 x 0.75
      mm, feed 4.1 mm, reconstruction thickness 1 mm, reconstruction increment 0.7 mm,
      kernel H60s for bone structures, or reconstruction thickness 4 mm, reconstruction
      increment 4 mm, kernel H31s for soft tissue structures. Secondary coronal and
      sagittal MPR's (multiplanar reconstructions) were then generated from original
      axial slices. No intravenous contrast media was required. Siemens CARE Dose 4D
      option was used to maximally reduce the X-ray dose. Since the aim of this study
      was to evaluate anatomical variations of sphenoidal sinuses septation only
      patients with no diseases within sphenoidal sinuses were included. All the
      subjects were Polish, with a mean age of 44 years, ranging from 18 to 84 years.
      RESULTS: In our study there was only one septum in 41%, two septa in 33%, three
      septa in 22% and four septa in 4%. The total amount of sinuses depending on total
      amount of septa (including accessory septa) and it can be different in the
      anterior and posterior part of the sphenoidal sinus. We also notice that the
      highest and the broadest septum (main septum) was completely bony in 57% whilst
      in 47% it was partially membranous. CONCLUSIONS: Performing CT of paranasal
      sinuses before surgery is essential to avoid potential complications resulting
      from anatomical variations.

PMID- 20687361
TI  - [Results of thrombolyses procedures in acute ischemic cerebral stroke realized in
      Krakow 2004-2007--Grant Ministry of Science and Information].
AB  - To lower the number of complications of acute cerebral ischemic stroke and to
      reduce the time of rehabilitation in these patients it is necessary to induce
      treatment within the first 3 hours of the onset of the stroke. Early intervention
      however, is possible only in cases with the confirm localized ischemic focus
      visualized in one of the diagnostic imaging methods. The most widespread is CT,
      hovewer the first symptoms of ischemic stroke can be seen not beforel2 hours of
      the onset. The study evaluated the effectiveness of early diagnostics of ischemic
      stroke using perfusion CT (pCT) with subsequent intravenous or intra-arterial
      thrombolysis. The patients with ischemic stroke confirmed by pCT and qualified to
      thrombolysis in the first 3 hours of the onset of the stroke were randomly
      selected to intravenous or intra-arterial thrmobolysis. Those, who were 3 to 6
      hours of the onset of the stroke were qualified to intra-arterial thrombolysis. A
      study group consisted of 377 patients hospitalized due to ischemic stroke. Of
      these pCT was performed in 76 cases, intravenous thrombolysis in 4 and intra
      arterial thrombolysis in 2. Clinical condition substantially improved in 3
      patients. Obtained results indicate the necessity to introduce pCT to the routine
      diagnostics of the acute ischemic stroke. A small number of patients eligible for
      thrombolysis does not allow to compare the effectiveness of intra-arterial and
      intravenous thrombolysis, however the project allowed to work out the efficient
      system of diagnostics and treatment of the acute ischemic stroke in the area of
      Krakow based on the standards used in the European countries.

PMID- 20687362
TI  - [Fibrous dysplasia of the scull discovered accidently on CT from different
      indication].
AB  - Fibrous dysplasia (dysplasia fibrosa -DF) is a local disorder of spongy bone
      structure caused by local pathological metabolism. Transformation of trabecular
      bony structure into connective tissue takes place. Inside the transformed bone
      scattered connective tissue elements, cartilaginous elements and pathological
      density are found. The disease proliferates either in the medullary bone or in
      subperiosteal region, and the development of fibrous tissue causes bone expansion
      with thinning of overlying cortex. The radiological appearance depends on the
      stage of the disease. The margins of the lesions are usually obscured and
      gradually turn into pathological tissue of trabeculated appearance. AIM OF THE
      STUDY: The aim of the study is to demonstrate fibrous dysplasia that is
      accidentally found during radiological diagnostics of facial skeleton and
      stomatological disease, and to describe radiological appearance of the
      pathological lesions. MATERIAL AND METHOD: The material included 23 patients (9
      males, 14 females), of 24 to 64 years of age, that were directed for the
      diagnostics of facial skeleton and stomatological disease with the use of
      multislice computer tomography, because of clinically diagnosed pathologies in
      the nasal sinuses, temporomandibular joints, pathologies of the mandible and
      maxillary, and before treatment with prosthetic implants. All the presented
      fibrous dysplasia cases were diagnosed during the performance of the above
      examinations. The examinations were performed by the use of spiral CT (Siemens
      Somatom Sensation 10) with standard parameters. The range of the examination
      included the nasal sinuses, facial skeleton or the whole scull-configuration of
      the detectors 10 x 0.75 mm, slice thickness 1 mm, reconstruction gap 0.7 mm,
      kernel H60s for osseous structure evaluation, and slice thickness 1, 4 do 4 mm,
      reconstruction gap 4 mm, kernel H31s for soft tissue evaluation. The obtained
      results were presented sented in the form of figures. RESULTS: In the analyzed
      material 23 cases of scull fibrous dysplasia were found. The disease involved 9
      males (39.14%) and 14 females (60.86%) from 24 to 64 years of age. Mean age for
      the whole group was 46.6 years, for males was 50,5 years and for females was 44.4
      years. Females with fibrous dysplasia were more numerous (60.86%) than males
      (39.14%). Monoostotic dysplasia was found in 18 cases (78,89%), polyostotic
      dysplasia was found in 4 cases (13.05%), the skull-face dysplasia was found in 9
      cases (14.07%). The radiological appearance is characterized by lesions that
      unclearly and gradually turn into pathological tissue with different densities,
      trabeculated appearance, and sclerotic, lytic or mixed structure. Early lesions
      usually have lower density than the normal surrounding bone, giving the
      appearance of translucency. CONCLUSIONS: Fibrous dysplasia of the facial skeleton
      is most commonly incidentally found on CT examinations of the head, mandible and
      nasal sinuses. Diagnosis of fibrous dysplasia is important because of unfavorable
      influence of the disease on stomatognathic system, laryngological disease,
      ophthalmic and neurological disease.

PMID- 20687363
TI  - [Accuracy analysis of computer tomography imaging for medical modeling purposes
      on the example of Siemens Sensation 10 scanner].
AB  - Medical model is a material model of human body part, used for better
      visualization or surgery planning. It may be produced by Rapid Prototyping
      method, based on data obtained during medical imaging (computer tomography--CT,
      magnetic resonance--MR). Important problem is to provide proper spatial accuracy
      of the model, influenced by imaging accuracy of CT and MR scanners. The aim of
      the study is the accuracy analysis of CT imaging for medical modeling purposes on
      the example of Siemens Sensation 10 scanner. Using stereolithography technique a
      physical pattern--phantom in the form of grating was produced. The phantom was
      measured by a Coordinate Measuring Machine Leitz PMM 12106 to consider production
      process inaccuracy. Then the phantom was examined using CT scanner Siemens
      Sensation 10. Phantom measurement error distribution was determined, based on the
      data obtained. Maximal measurement error, considering both phantom production
      inaccuracy and CT imaging inaccuracy was +/- 0.87 mm, while considering only CT
      imaging inaccuracy was not exceeding 0.28 mm. CT acquisition process is by itself
      the source of measurement errors. So to provide high quality of medical models
      produced by Rapid Prototyping methods, it is necessary to perform accuracy
      measurements for every CT scanner used for obtaing data serving as the base for
      model production.

PMID- 20687364
TI  - [Application 3D DSA and angiographic CT in interventional neuroradiology].
AB  - AIM: Modern angiographs used in interventional neuroradiology are equipped with
      advanced imaging techniques like three-dimensional angiography (3D DSA) and
      Angiographic CT. The aim of this paper is presentation of application these
      methods based on our experience. METHOD: Both method--Angiographic CT and 3D DSA-
      use "C" arm rotation technique around the patient. Obtained data are processed to
      three-dimensional images (in 3D DSA) or (in Angiographic CT) to computer
      tomography (CT)--like reconstruction: multiplanar (MPR), maximum intensity (MIP)
      and volume rendering (VR). DISCUSSION: Angiography 3D DSA is nowadays a basic
      method in diagnostics of cerebral aneurysms. Three-dimensional images allow for
      precise evaluation of the aneurysm, qualification for treatment, facilitate
      embolisation procedures and evaluation of efficiency of the treatment.
      Angiographic CT (like CT) allows for evaluation of the most important brain
      structures like: ventricular system, subarachnoid cisterns and less brain tissue.
      The main application of this technique is evaluation of endo-vascular procedures
      in respect of hemorrhagic complications. Possibility of quick imaging of the
      brain and detection of intracranial hematoma, intraventricular hemorrhage with
      developing hydrocephalus, brain edema, allows for immediately reaction.
      CONCLUSION: 3D DSA and Angiographic CT are methods which in interventional
      neuroradiology make easier preparing the diagnosis of vascular pathologies and
      performing intravascular treatment. Angiographic CT allows for quick evaluation
      of potential complications after endovascular procedures without transfer patient
      outside angiographic room.

PMID- 20687365
TI  - [The role of MRI in the assessment of the cardiac anatomy and function].
AB  - This paper discusses the role of MRI in the assessment of the cardiac anatomy and
      function. Cardiac MRI offers the possibility of precise quantitative heart
      evaluation (also in measuring the volume and mass of the heart ventricles). It is
      characterised by high reproducibility compared with that of echocardiography. For
      the assessment of the heart and the great vessels the Spin Echo and Fast Spin
      Echo sequences are used. The observation of the heart function is possible in
      Gradient Echo sequences, in the cine mode. Contrast enhancement sequences allow
      the assessment of the heart perfusion, the detection and scope of ischaemic area
      and post-infarction scar as well as the differentiation between necrotic tissue
      from stunned muscle. In many cardiac conditions MRI may play an important role.
      They include ischaemic heart disease, cardiomyopathies, cardiac defects and less
      common pathologies such as tumours, sarcoidosis, amyloidosis and
      haemochromatosis. The use of cardiac MRI in the diagnostics of those conditions
      is discussed.

PMID- 20687366
TI  - [Fusion SPECT/CT in clinical practice].
AB  - Fusion consists in a combination of images obtained using different diagnostic
      techniques, usually functional (SPECT, PET) and structural (CT, MR) imaging. It
      may be performed as a software fusion of images obtained not the same time by
      different devices or as a hardware fusion of images obtained the same time using
      as a hybrid system enabling both the functional and structural imaging (SPECT/CT,
      PET/CT). Fusion enables precise anatomical location of lesions detected by SPECT,
      functional verification of lesions found by CT. It is a useful tool in the
      assessment of effectiveness and dosimetry for radioisotopic therapy. Additionally
      fusion of functional and structural examinations reduces diagnostic difficulties
      appearing in independent interpretation. In spite of inconveniences resulting
      from technical aspects of software fusion (positioning differences, spontaneous
      movements of internal organs) it is more and more commonly used in clinical
      practice in centers not possessing hybrid systems.

PMID- 20687367
TI  - [Standardisation of the MRI and US images evaluation in the diagnostics of
      rheumatoid arthritis within the wrist and metacarpophalangeal joints].
AB  - In Rheumatoid arthritis (RA) it is very important to recognize pathologic
      condition and to start proper treatment as early as possible to lessen its
      consequences. Currently, magnetic resonance imaging and ultrasonography are the
      best imaging modalities because they depict early stages of this disease and
      allows to control response to treatment. MRI depicts also bone oedema, which is a
      strong predictor of further progression. The process of standardization is needed
      in assessing both MR and US pictures. Standardization allows to compared both
      examinations of the same patient in different time and examinations of different
      patients. An aim of this article is to present: MR protocols of hand and wrist MR
      examinations for rheumatologic demand and standards of results, according to
      worldwide OMERAC RAMRIS 2002 and supplemented by tenosynovitis system; proposals
      for US examination of hands in rheumatoid patients.

PMID- 20687368
TI  - [Presurgical functional brain examination MR (fMRI)].
AB  - Neurosurgery in functionally relevant brain structures carries a high risk for
      surgery induced post-operative neurological deficits. Functional magnetic
      resonance imaging (fMRI) is one of the most commonly used functional neuroimaging
      techniques for pre-surgical brain mapping. Preoperative fMRI is optimal method to
      localize specific functions of the human brain that govern motor, sensory or
      language functions. fMRI facilitates the selection of the safest treatment and is
      very helpful to plane and to perform function preserving surgery in patients with
      brain tumors. This kind of examination is feasible for clinical routine
      neuroimaging and provides important diagnostic information noninvasively that is
      otherwise unavailable. fMRI examinations require also advanced software for data
      analysis.

PMID- 20687369
TI  - [Three-dimentiolanl moving-table MR angiography in diagnostic of peripheral
      arteria diseases].
AB  - PURPOSE: The aim of this study was to present the method of three-dimentional
      contrast-enhanced moving-table MR angiography, on the basis of own experience.
      METHOD: The 1,5T MR system with moving-table option was used to examin pelvic and
      peripheral arteries of lower extremities. The body coil was used. The large
      region of interest was divided into three segments: TOP--pelvis, MID--thight and
      BOT--leg. MR aquisitions were performed in coronal plane after injection of
      contrast, given by the automatic two-chamber syringe. Programm IVI were used to
      obtain 3D reconstructions. CONCLUSION: Three-dimentional contrast-enhanced moving
      table MR angiography is accurate, noninvasive diagnostic method for evaluation of
      peripheral arterial diseases of lower extremities and allows to choose an
      adequate method of treatment.

PMID- 20687370
TI  - [Walery Jaworski--the founder of the Cracovian school of radiology].
AB  - Diagnostic imaging is one of the most evolving branch of medicine. Its
      development was started by X-ray invention (W. K. Roengen in 1895). Among Polish
      and worldwide pioneers of radiology there was prof. Walery Jaworski, who is known
      mainly as a "father" of Polish gastrology and a discoverer of Helicobacter
      pylori. The aim of this article is to remind Professor's merits to Polish and
      worldwide radiology.

PMID- 20687371
TI  - [Radiographic examinations of flowers].
AB  - The aim of the study is to present utility of the mammography to obtain flowers'
      radiograms.

PMID- 20687372
TI  - [Electrophysiological diagnosis of severe carpal tunnel syndrome in patients on
      maintenance hemodialysis with created arterio-venous fistula and concomitant
      polyneuropathy].
AB  - Carpal tunnel syndrome (CTS) is the most frequent neuropathy observed in
      maintenance haemodialysis patients. In spite of the established diagnostic
      guidelines and many different methods of nerve conduction testing, sometimes
      difficult to distinguish very advanced CTS (absent median motor and sensory
      responses) from uremic neuropathy. In the last few years the 2LI-DML test has
      been accepted as a reliable method for the diagnosis for very advanced stage of
      CTS. The aim of this study was to evaluate the usefulness of nerve conduction
      testing based on the interlatency difference (2LI-DML) between the second
      lumbrical (2L) and second dorsal interosseous (21) muscles in the diagnosis of
      severe forms of carpal tunnel syndrome in long-term hemodialysis patients with
      superimposed polyneuropathy. From the group of 40 patients with CTS the 2LI-DML
      test was used in five cases of long-term hemodialysis with severe damage of the
      median nerves (absent median motor and sensory responses) and with forearm
      arteriovenous fistulas and concomitant uremic polyneuropathy. The presence of
      forearm arteriovenous fistulas makes needle electrode test impossible to apply.
      The performed 2LI-DML test allowed for a confirmation of clinical diagnosis of
      CTS in all the patients. A mean difference of motor latency between the second
      lumbrical and the second interosseous muscles was significantly prolonged and
      amounted to 10.91+2.36 ms. CONCLUSIONS: The 2LI-DML test is the only test that
      may be used to diagnose CTS in patients with severe damage of the median nerves
      and with forearm arterio-venous fistulas and superimposed polyneuropathy. The
      test is fast, simple to perform and well-tolerated by such patients.

PMID- 20687373
TI  - [Neurological complications among patients with zoster hospitalized in Department
      of Infectious Diseases in Cracow in 2001-2006].
AB  - BACKGROUND: Herpes zoster is an infectious disease caused by varicella zoster
      virus (VZV). After replication at the place of entry, VZV spreads via the blood
      into the skin and mucosa, causing the varicella. From these regions VZV migrates
      into the sensory ganglia where it establishes a latent infection. The aim of our
      study was to analyze the localization of the skin changes and correlations of
      neurological complications among patient with zoster. MATERIAL AND METHODS: We
      have reviewed medical documentation of the 67 patients with herpes zoster,
      hospitalized in our Department during the years 2001-2006. We have studied
      localization of the herpes zoster changes and frequency of neurological
      complications among these patients. RESULTS: Neuralgia was less intensive and
      last shorter time, when antiviral treatment had been started earlier. Neuralgia,
      meningitis, encephalitis and complications of the eye zoster were present more
      often among patients over 65 years old.

PMID- 20687374
TI  - [Role of the M235T (c.704c>T) polymorphism of angiotensynogen gene as well as
      A724A (c.2171G>A) polymorphism of SERCA2a gene in ethiopathogenesis of left
      ventricular hypertrophy in essential hypertension].
AB  - Left ventricle hypertrophy (LVH) is main organ complication developing in the
      course of primary hypertension. Among 'candidates genes' related with development
      of hypertension as well as LVH; the promoting, but not crucial, influence of
      (c.704C>T) angiotensinogen (AGT) gene was found. The elevated calcium ions
      concentration in the cytosol of muscle cells, might be one of the element in the
      ethiopatomechanism of essential hypertension development. The ATP-related ions
      pomp--SERCA2A regulates the intracellular calcium concentration. Mutations in the
      ATP2A2 gene coding the SERCA2A protein, has been associated with elevated calcium
      level in cardiomyocytes. The aim of the study was to analyze frequency of the
      M235T (c.704C>T) AGT gene polymorphism. The new mutations in the ATP2A2 gene was
      searched for in hypertensive patients, independently to the LVH presence in
      compare to the control group. 157 people participated in the study. Based on the
      echo-cardiographic examination participants were divided into subgroups: patients
      with essential hypertension (NT) and patients with NT and LVH. 50 healthy
      volunteers served as the control group. The frequency of the CC homozygotes, of
      the M235T (c.704C>T) AGT gene polymorphism, was the highest in the patients with
      essential hypertension and LVH in compare with patients without LVH (p = 0.67)
      and control group (p = 0.64). The value of the LVMI was the highest in CC
      carriers in compare to homozygotes TT (p = 0.33) and CT group (p = 0.66). In
      homozygotes TT as well as in the carriers of allel T, the elevated blood
      pressures value was detected. In the exon 15 of ATPA2A gene the new polymorphism
      A724A (C.2171G>A) was found. only the presence of GG and heterozygotes GA was
      detected in analyzed group. The frequency of GA genotype was significantly higher
      in control group vs patients with essential hypertension with (p = 0.05)/or
      without LVH (p = 0.04). The GA carriers had lower blood pressures values measured
      in doctor office as well as using ABPM method. The LVM as well as LVMI values
      were lower in group with mutated genotype GA in compare to GG group (p = 0.107
      for LVM; p = 0.154 for LVMI). Results suggest a protective role of the c.2171G>A
      polymorphism of the ATP2A2 gene against the hypertension as well as LVH
      development. It seems also that c.704C>T polymorphism of AGT gene does not play
      crucial role in the essential hypertension development.

PMID- 20687375
TI  - [Risk of the first degree atrioventricular block during atrial pacing in patients
      with sick sinus syndrome].
AB  - BACKGROUND: Permanent cardiac pacing is applied in symptomatic cases of sick
      sinus syndrome (SSS). The aim of our research was to characterize a group of
      patients suffering from SSS with low risk of developing into the first degree
      atrioventricular block (AVB), who are able to have the atrial pacemaker (AAI)
      implanted. METHODS: 243 patients (mean aged 61.8 years, 22.7-90.3) with implanted
      AAI pacemaker due to SSS were qualified. The PQ interval was compared in the
      earliest found (1-119 months from implantation, SD +/- 2.7 m) and the last
      control examination of each patient. Mean follow-up time was 88,8 months. We took
      into consideration the age at the moment of implantation, basic rhythm rate,
      polarity of the stimulating electrode (unipolar/bipolar), and presence or absence
      of "rate response" option. RESULTS: During the follow-up the PQ interval
      prolonged in 40.4% of patients, on average by 36 ms, did not change in 42.1%, and
      in 17.5% contracted, on average by 30 ms. The age differences of these groups
      were not statistically significant. Prolongation of PQ in atrial pacing was
      rather sudden than linear, below the certain age changes of PQ are slight and
      after going beyond this age it increases visibly. In our patients this crucial
      age is 60-70. Presence of "rate response", polarity of the stimulating electrode,
      basic rhythm rate did not have any influence on PQ changes. The 1st degree AVB
      has been developed almost in a half of our group of patients. They had longer,
      almost border PQ in the first examination (mean 196 ms, SD +/- 29 vs. 166 ms, SD
      +/- 24; p < 0.001). During on average 63 months long observation the PQ interval
      became longer on average by next 23 ms. In the rest of patients, during the
      comparable time period PQ did not change. The differences of PQ changes between
      these groups were strongly statistically significant (p < 0.001). The 1st degree
      AVB occurred in 20% of patients with initial PQ < or = 160 ms and in 53% of
      patients with longer PQ. CONCLUSIONS: 1. The 1st degree AVB in the group of
      patients in 7th-8th decade of their lives, regardless of patients' sex, treated
      with permanent AAI pacing, develops usually when PQ reaches the upper borderline
      of standard range in the examination at the starting point. 2. In people with
      initially short PQ interval (< or = 160 ms) there is low risk of the 1st degree
      AVB.

PMID- 20687376
TI  - [One year observation of natural course of aortic valve stenosis in patients with
      normal and abnormal lipoprotein (a) plasma level].
AB  - AIM: The observation of natural course of aortic valvae stenosis (AVS) in
      patients with high lipoprotein (a) [Lp(a)]. PATIENTS: 60 AVS patients who did not
      agree for operational treatment were divided into group A (n = 19) with high
      serum Lp(a) level and into group B (n = 41) with normal plasma Lp(a) level.
      METHODS: Plasma Lp(a), total cholesterol, HDL-cholesterol, LDL-cholesterol,
      triglycerides and C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis
      factor (TNF-alpha) as well as titers of immunoglobulin (Ig) class G, A, M against
      chlamydia pneumoniae were measured every 12 months. Echocardiographic evaluation
      of aortic valve was also done every 12 months. RESULTS: Means serum CRP at 12
      month was higher in group A. Mean serum TNF-alpha level was also higher at visit
      I and at 12 month (visit II) in group A. Mean serum IL-6 level did not differ
      between groups. IgG titer was higher in group A at visit I and visit II. At 12
      month of observation HDL-cholesterol plasma level was lower in group A. HDL/total
      cholesterol ratio as well as HDL/LDL-cholesterol ratio was laso lower in group A
      at 12 month of observation. No statistically significant differences in
      echocardiographic parameters were founf between groups. CONCLUSION: The results
      may suggest risk factors similarity of AVS and atherosclerosis.

PMID- 20687377
TI  - [Serum iron level in the patients with inflammatory abdominal diseases].
AB  - In our study we investigated serum iron levels in the patients with localized or
      generalized peritonitis. These values were compared in group of 52 patients with
      acute peritonitis against group of 39 patients without inflammation within
      peritoneal cavity. The serum iron levels and Total Iron Binding Capacity (TIBC)
      was indicated in both group. Acute intraabdominal inflammation induced in all
      patients a state of hypoferremia. However, medium decline of iron level in
      patients with acute appendicitis or cholecystitis was smaller compare with that
      observed among the patients with generalized peritonitis caused by perforation of
      duodenal ulcer, perforation of large bowel diverticula or perforation of small
      bowel. It has been suggested that decline in iron serum level observed in those
      patients can be an element of metabolic response to trauma and represents a part
      of the innate immune system and thus constitutes the first line defence against
      infection. However, based on presently available knowledge we can not yet finally
      evaluate the clinical implication of serum iron monitoring in diagnosis and
      prognosis of the patients with peritonitis.

PMID- 20687378
TI  - [Retrospective assessment of health and locomotor efficiency in elderly patients
      in the period directly preceding femoral trochanter fracture].
AB  - This paper presents a group of patients which had femoral trochanter fracture.
      The study group was assessed in terms of age, sex, concomitant diseases and pre
      traumatic motor efficiency. The author of the paper highlights the fact that the
      majority (42%) of patients is over 80 years of age, and frequently suffer from
      two or more concomitant diseases impeding the surgical procedure in the emergency
      mode. Moreover almost every second person had significant problems with movement
      before the fracture.

PMID- 20687379
TI  - [Analysis of annual mortality rate in elderly patients with femoral trochanter
      fractures treated surgically].
AB  - A higher mortality rate is observed in patients with femoral trochanter fractures
      than in patients with femoral cervix fractures. Moreover, a statistically higher
      incidence of chronic diseases has also been observed in this group. Multifactor
      analysis of annual mortality rate after fracture and connection of the femoral
      trochanter area in elderly patients was carried out by the author of this paper
      on the basis of the regressive model. The analysis has shown that the mortality
      rate is significantly influenced by unstable type of fracture, improper pre
      traumatic activity and the presence of circulatory diseases. The observed
      mortality rate has not been related to the patients' age or to the type of the
      implant used for fracture connection.

PMID- 20687380
TI  - [Hiperbilirubinemia- one of the high risk factor influence on hearing level in
      infants].
AB  - Hiperbilirubinemia is one of the high risk factor of hearing loss of infants.
      Hearing loss is present in 60 per cent children with high level of bilirubina in
      blood serum. The aim of the article is to see how the level of bilirubina,
      influence on hearing loss. The level of bilirubina in blood serum was marked in
      children after born and while next hospitalisation. Audiologic diagnosis and
      otolaryngological examination were done as well. Hiperbilirubinemia was the only
      one factor of high risk of hearing loss in this group. The analysis of 53
      patients showed that separate high level of bilirubina does not influence on
      hearing loss in children.

PMID- 20687381
TI  - [The analysis of epidemiology, clinical symptoms, serological tests in the course
      of borreliosis].
AB  - BACKGROUND: Lyme disease is an animal-borne disease, caused by spirochetes of the
      Borrelia burgdorferi (Bb). The infection is transmitted by ticks of the Ixodes
      ricinus species. Humans are infected through a tick bite to the skin. The aim of
      the study was evaluation of epidemiology, symptoms and serologic factors in Lyme
      disease. MATERIAL AND METHODS: We have enrolled 39 patients from Malopolska
      region in the study treated for Lyme borreliosis. History of tick biting,
      clinical signs and symptoms and serological tests were evaluated. RESULTS: The
      most common symptoms were headaches and pain of the large joints. Patients with
      untreated erithema migrans (EM) more often developed symptoms from nervous system
      (83%) than joints (54%). We found abnormalities which confirmed inflammation in
      CSF in 24.3% of patients. Patients with positive IgG antibodies against Bb in CSF
      and confirmed their intrathecal synthesis had never had EM in the past.
      CONCLUSIONS: There is low percentage of the patients who were treated due to EM.
      Patients with untreated EM more often developed symptoms from nervous system than
      joints. The most common symptoms among our patients were headaches and pain of
      large joints.

PMID- 20687382
TI  - [The plasma level of sL-selectin, myeloperoxidase (MPO) and granulocyte-colony
      stimulating factor (G-CSF) in gynecological cancer patients].
AB  - It is known that G-CSF not only stimulates the granulopoiesis but also regulates
      the functions of mature neutrophils. Indirect evidence of this might be the
      increase of the activity of granulocyte enzymes participating in phagocytosis and
      killing tumor cells. The purpose of this investigation was to evaluate in the
      plasma of breast cancer patients the level of adhesion molecule--sL-selectin, as
      a measure of maturate granulocyte activity and MPO--enzyme of granulocyte,
      responsible for the cytotoxicity. Additionally we have investigated the plasma
      level of G-CSF which can increase in the cancers. We tested 17 patients with I
      stage endometrial cancer and 19 patients with I stage cervical cancer. Plasma
      samples were drawn before operation. The control group consisted of 20 healthy
      women. The plasma levels of sL-selectin, myeloperoxidase and G-CSF were measured
      using a sensitive sandwich ELISA system. In gynecological cancer patients sL
      selectin concentration was decreased, but myeloperoxidase concentration increased
      in comparison to the control group. G-CSF level in group with endometrial cancer
      was similar to the control group, but in group with cervical cancer was
      significantly lower. These results suggest that ability of granulocyte binding to
      cancer cells is decreased but cytotoxicity is increased, at lack of stimulation
      by of G-CSF.

PMID- 20687383
TI  - [Pure red cell aplasia (PRCA) induced by anti-EPO antibodies: epidemiology,
      diagnosis and treatment].
AB  - Pure red-cell aplasia (PRCA) is a serious, life threatening rare condition of
      multifactorial causes manifested as severe anemia with absence of erythroid
      precursors in the bone marrow. PRCA may be a consequence of antibody production
      against applied recombinant human erythropoietin (EPO). The first description of
      PRCA in the course of EPO therapy was performed in a patient receiving
      subcutaneously Eprex and in the next years after therapy with other
      erythropoiesis stimulating agents like erythropoietin beta, omega or darbepoetin.
      In the paper we describe epidemiology and diagnostic criteria of PRCA. The
      current treatment possibilities of this complication were described with special
      attention dedicated to different immunosuppressive agents and effectiveness of
      kidney transplantation with subsequent immunosuppression.

PMID- 20687384
TI  - [Pituitary disorders in pregnancy and after delivery].
AB  - Pregnancy is associated with a number of changes in endocrine physiology that
      substantially alter hormone levels and affect a number of disease processes.
      Consequently, both pregnancy and the postpartum period may influence the course
      of pre-existing pituitary disorders and lead to the development of those that are
      found exclusively or almost exclusively during these periods. Overlapping
      clinical and biochemical features of pregnancy sometimes cause that the diagnosis
      of pituitary disorders during pregnancy may be missed. Moreover, their clinical
      picture may range from non-specific symptoms to even life-threatening conditions,
      and the manifestation of the same pituitary disease often change from one patient
      to another. If not evaluated and managed appropriately, these disorders may
      negatively affect both mother and fetus. The purpose of this review is to provide
      an update on the pathophysiology, clinical picture, diagnosis and treatment of
      different pituitary disorders during pregnancy and after delivery. The reader is
      also provided with some practical recommendations on dealing with pregnant and
      nursing women suffering from these disorders.

PMID- 20687385
TI  - [Use of magnetic resonance in the diagnostics of ischemic heart disease].
AB  - The role of magnetic resonance imaging (MRI) as a diagnostic tool of coronary
      arteries disease has increased over the last years. Cardiac magnetic resonance
      (CMR) is a preferable tool in assessment of ventricular mass and function,
      presence and size of post infarct scaring and anomalies of coronary arteries. CMR
      becomes also a useful method in evaluation of myocardial viability. Examination
      with gadolinium dye allows for evaluation of myocardial perfusion and viability.
      The extent of the post infarct late enhancement zone has an important prognostic
      value in the recovery of the left ventricle function. Dobutamine, adenosine or
      dypirydamol stress CMR becomes a promising noninvasive diagnostic modality in
      detection of coronary artery disease. At present coronary arteries magnetic
      resonance angiography is being developed as well as CMR spectroscopy.

PMID- 20687386
TI  - [Anticonvulsant and neuroprotective effects of the ketogenic diet].
AB  - Ketogenic diet has been used in treating epilepsy for more than 80 years. It is
      based on a drastic change of proportions in the consumption of carbohydrates,
      proteins and fats. In everyday diet we consume approximately 34 per cent of fats,
      50 per cent of carbohydrates and 14 per cent of proteins. While ketogenic diet
      consists in 80-90 per cent of fats and in 10-20 per cents of carbohydrates and
      proteins together. Despite its indisputable effectiveness, the functioning of the
      ketogenic diet has not been explained. It seems that its functioning mechanism is
      unique and results from a number of chronic metabolic changes as well as the
      adaptation in the cenral nervous system that occurs during its long-term
      application. The most recent clinical and experimental data suggest that the
      ketogenic diet also has neuroprotective properties, which makes it a useful
      alternative therapeutic method in the modification of the natural history of the
      diseases related with neurodegeneration processes.

PMID- 20687387
TI  - [Evaluation of chosen salivary periodontal disease markers].
AB  - There are articles showing promise on diagnostic use of pro-inflammatory markers
      in certain body fluids. Research on pathogenesis of periodontal diseases concerns
      evaluation of biochemical and immunological factors in context of their influence
      on severity, progress and prognosis of the disease. The methods comprised of
      saliva, gingival sulcus fluid and traditionally serum. THE AIM OF THE STUDY:
      Contemporary view on possibilities of evaluation of some salivary factors in
      aspect of making periodontal diagnosis and monitoring of this disease was
      presented, on the basis of chosen literature. Authors evaluated factors such as:
      host proteins, phenotypic markers, host cells, hormones, bacteria and bacterial
      products, ions and volatile compounds. Factors in neutrophils, free radicals and
      significance of oxidative stress, platelet-activating factor (PAF), vascular
      endothelial growth factor (VEGF), neopterin and immunoglobulins activity, also
      their role in periodontal pathogenesis, were described. It was concluded, that
      longer-term, well controlled clinical studies in bigger population should be
      performed, to confirm significance of specific saliva markers for diagnosis and
      monitoring of periodontitis and other lesions in oral cavity.

PMID- 20687388
TI  - [Thrombotic complications of central venous catheters in hematooncological
      patients].
AB  - Central venous catheters (CVC) are frequently used in patients with a
      hematological disorders in order to administer drugs, stem cell infusions, blood
      products, parenteral alimentation as well as for blood sampling. There are known
      mechanical, infectious and thrombotic complications of central venous catheters
      in hematological patients. Infectious and thrombotic complications have been
      considered as separate entities so far, but there are theory and accumulating
      evidence that they are interrelated. Since data on central venous catheters
      related thrombosis in hematological patients have been obtained mainly from
      retrospective studies of small size, prospective randomized studies are
      warranted. In this review we present current opinions about epidemiology,
      pathogenesis, diagnosis of CVC-related thrombosis and also its correlations with
      infectious CVC-related complications.

PMID- 20687389
TI  - [Pseudo-Bartter syndrome--2 cases].
AB  - Bartter syndrome represents the group of renal disturbances characterized by
      hypokaliemia and metabolic alkalosis. Some diseases could display hypokalemic
      metabolic alkalosis without primary tubular dysfunction. These disorders are
      called pseudo-Bartter syndrome. In this paper we present 2 cases of pseudo
      Bartter syndrome related among to other things to overuse of diuretic drugs.

PMID- 20687390
TI  - [Possibilities of orthopaedic treatment of patients with renal failure and its
      meaning in the continuation of haemodialysis and quality of life improvement].
AB  - Good cooperation between the fields of orthopaedic surgery and nephrology creates
      a possibility of multidirectional surgical treatment of the patients with
      terminal renal failure despite massive general burden and existing risk. Taking a
      very difficult decision concerning the multidirectional surgical treatment of
      these patients may to a very great extent improve their locomotor functions and
      their life comfort. An example of such a situation is the described case of elbow
      replacement, vascular surgery procedure, total hip replacement and carpal tunnel
      release surgery.

PMID- 20687391
TI  - [Breaking bad news--information for doctors].
AB  - The article broaches the subject of breaking bad news. Medical doctors deal with
      such a problem frequently, not always well-prepared for their role. Obviously,
      each patient should be treated individually, not only because every disease is a
      unique case, but also because patients have their own hopes and expectations. In
      order to conduct a discussion containing bad news, it is worth to base on the
      scheme presented in the article. Preparation for the meeting is crucial. Besides
      the fact that it facilitates the dialogue, it also enables presenting information
      in the right way. Firstly, it is important to listen to the patient carefully,
      clarify his concerns and then answer all his questions and doubt. Next, if the
      patient is willing, the doctor should discuss the state of health, possible
      therapies and prognosis. The end of the talk should consist of appropriate
      summary and the date of the next meeting. The article emphasize that truth and
      reliability are extremely significant in contact with a patient. Moreover, it
      presents the area of information which can be talked about with the family. The
      authors try to approach the dialogue which contains bad news, reveal various
      possibility of conducting the discussion and dealing with problems.

PMID- 20687392
TI  - [Opinion by Professor J. Olbrycht and Dr Marian Kusiak after examination of the
      skull of St. Stanislaus --a criminalistic and forensic interpretation].
AB  - In June 1963 the Bishop of Cracow Karol Wojtyla approached Professor Jan Olbrycht
      (Chair of the Department of Forensic Medicine, Cracow Medical Academy) with the
      request to examine the reliquary and skull of St. Stanislaus. The examination was
      carried out by J. Olbrycht and M. Kusiak and the results published. Included in
      this article are the interpretations of these opinions by a criminologist and two
      forensic physicians. One of the forensic physicians (Z. Marek) acknowledged that
      there was a case of unauthorized misinterpretation of Professor Olbrycht's
      statement.

PMID- 20687393
TI  - Increasing world incidence of thyroid cancer: increased detection or higher
      radiation exposure?

PMID- 20687394
TI  - Autoimmunity in differentiated thyroid cancer: significance and related clinical
      problems.
AB  - Coexistence of differentiated thyroid cancer (DTC) and thyroid autoimmune
      diseases could represent a mere coincidence due to the frequent occurrence of
      autoimmunity, but there may also be a pathological and causative link between the
      two conditions. The coincidence of DTC with Hashimoto's disease has been variably
      reported at between 0.5 and 22.5% and of DTC with Graves' disease between 0 and
      9.8%. In this review available evidence for thyroid autoimmunity in DTC is
      summarized and it is concluded that thyroid cancer does coexist with thyroid
      autoimmunity, implying that patients treated for autoimmune thyroid diseases
      should have a careful follow-up. Furthermore, the presence of thyroglobulin
      antibodies (TgAb) in patients with DTC may limit the use of serum thyroglobulin
      as a tumor marker due to methodological problems in the determination of serum
      thyroglobulin. However, in such cases serial TgAb measurements may be used as a
      surrogate marker for recurrence of thyroid cancer during the long-term monitoring
      of DTC patients.

PMID- 20687395
TI  - Bisphenol-A: a new diabetogenic factor?
AB  - The aim of this review was to analyze the potential effects of environmental
      chemicals on homeostatic control related to glycemia and energy balance. Many of
      the environmental chemicals can mimic or interfere with the action of hormones
      and are generally referred to as "endocrine disruptors". Among these compounds,
      polychlorinated biphenyls, dioxins, phthalates and bisphenol-A have been
      correlated with alterations in blood glucose homeostasis in humans. In rodents it
      has been demonstrated that small doses of bisphenol-A have profound effects on
      glucose metabolism. Therefore, this altered blood glucose homeostasis may enhance
      the development of type 2 diabetes.

PMID- 20687396
TI  - Hormone therapy and asymmetrical dimethylarginine in postmenopausal women.
AB  - Women present an estradiol-dependent cardiovascular risk profile. Based on
      various studies, it was considered that estrogen therapy (ET) in postmenopausal
      women could probably reduce the higher cardiovascular risk in this group.
      Assymetric dimethylarginine (ADMA) is an endogenous methylated arginine which
      inhibits nitric oxide (NO) synthesis by competing with the substrate of NO, L
      arginine, leading to endothelial dysfunction and, consequently, to
      atherosclerosis. Moreover, ADMA has been considered as an independent risk factor
      for cardiovascular disease. It has also been found that hormone therapy (HT), and
      mainly oral estrogen therapy, lowers ADMA concentrations in healthy
      postmenopausal women. The effect of estrogens on ADMA levels, although small, is
      considered important, as physiological variation of ADMA is limited.
      Nevertheless, larger randomized trials are necessary to establish that estrogens
      substantially lower ADMA levels and that these changes really reflect improved
      cardiovascular prognosis in postmenopausal women.

PMID- 20687397
TI  - The interrelationship of serum 1,25-dihydroxyvitamin D, 25-hydroxyvitamin D and
      24,25-dihydroxyvitamin D in pregnancy at term: a meta-analysis.
AB  - OBJECTIVE: To assess the relationship between circulating 25(OH)D, 1,25(OH)2D,
      and 24,25(OH)2D in pregnancy at term, and to test the hypothesis that serum
      25(OH)D and 24,25(OH)2D are repressed by high serum 1,25(OH)2D levels. DESIGN:
      Twenty studies in pregnant women at term and 14 studies in young non-pregnant
      women were selected from the electronic literature. From these studies the mean
      serum concentrations of 25(OH)D, 1,25(OH)2D, and 24,25(OH)2D from 26 groups of
      pregnant and 14 groups of non-pregnant young women were analyzed. The grand mean
      (mean of the means) of serum 25(OH)D, serum 1,25(OH)2D, and of the ratio
      1,25(OH)2D/25(OH)D were compared between pregnant and non-pregnant women. Also,
      the means of serum 1,25(OH)2D were regressed on the means of serum 25(OH)D. The
      relationship between 25(OH)D and 24,25(OH)2D was also evaluated using similar
      methods. RESULTS: The grand mean of 1,25(OH)2D was two-fold higher, and the grand
      mean of the ratio 1,25(OH)2D/25(OH)D was 2.5-fold higher in pregnant than in non
      pregnant women with comparable serum 25(OH)D. Regression showed no significant
      relationship between 1,25(OH)2D and 25(OH)D in pregnant and non-pregnant women.
      The ratio 24,25(OH)2D/25(OH)D was not different in pregnant and non-pregnanat
      women. Regression showed significant relationship between 24,25(OH)2D and 25(OH)D
      in both pregnant and nonpregnant women. CONCLUSIONS: Serum 1,25(OH)2D is not,
      whereas serum 24,25(OH)2D is significantly related to serum 25(OH)D in pregnant
      women. Serum 24,25(OH)2D seems not to be repressed by the high 1,25(OH)2D levels
      during pregnancy, whereas a similar conclusion for 25(OH)D is less clear.

PMID- 20687398
TI  - Subcutaneous glucose monitoring with GlucoDay: comparison of the results to those
      obtained with the endocrine artificial pancreas.
AB  - OBJECTIVE: This study was undertaken to assess the accuracy of GlucoDay- a
      portable detector of subcutaneous glucose--by comparing the results to those
      obtained by Biostator an established and reliable method for continuous glucose
      measurement in whole blood. DESIGN: Subjects with type 1 diabetes (n:6), subjects
      with type 2 diabetes (n:6), and six healthy controls were studied for 24 hours;
      they consumed three main meals. The GlucoDay was connected to the subjects by
      inserting a microfibre probe into the periumbilical subcutaneous area, whilst the
      Biostator was inserted by a double-lumen catheter into an antecubital vein. A
      third catheter was inserted into a separate vein for blood withdrawal to measure
      glucose by the hexokinase method. RESULTS: The three methods (GlucoDay-Biostator
      hexokinase) were equally accurate in measuring glucose levels (p = 0.233,
      Kruskall-Wallis test). The glucose measurements performed with GlucoDay and
      Biostator were significantly correlated with those performed with hexokinase (p <
      0.001, r2 = 66.65% and p < 0.001, r2 = 64.4%, respectively, using simple
      regression analysis). CONCLUSIONS: Measurements of glucose fluctuations in the
      subcutaneous tissue with the GlucoDay were close to those in blood determined by
      the Biostator. GlucoDay is therefore a reliable method for continuous glucose
      monitoring and may prove useful for optimizating treatment in patients with type
      1 or type 2 diabetes.

PMID- 20687399
TI  - Iodine content of thyroglobulin in Nod.H2h4 mice developing iodine-accelerated
      autoimmune thyroiditis.
AB  - OBJECTIVE: In NOD.H2h4 mice, high dietary iodine intake has been known to cause
      iodine-accelerated spontaneous autoimmune thyroiditis (ISAT) via an unknown
      mechanism. The aim of the study was to examine whether the NOD.H2h4 genetic
      background predisposes to enhanced iodine organification in thyroglobulin (Tg), a
      target autoantigen in ISAT. DESIGN: To avoid issues associated with an ongoing
      anti-Tg antibody response, we assessed Tg iodination levels in iodine-fed, B-cell
      deficient NOD.H2h4 mice. Additionally, we tested whether humoral or cellular
      immune responses of iodine-fed NOD.H2h4 mice are preferentially directed to Tg
      with increased iodine content (I-Tg) or known pathogenic Tg peptides that
      contained iodine. RESULTS: The iodine content of Tg was not significantly
      different between control (9.0 +/- 2.7 I atoms per monomer) and iodine-fed mice
      (10.9 +/- 0.3 I atoms per monomer). Furthermore, in iodine-fed NOD.H2h4 mice
      developing ISAT, strong but equivalent serum IgG responses were detected to both
      Tg or I-Tg, whereas their lymphoid cells were stimulated weakly but equally well
      by Tg or I-Tg in vitro and did not show reactivity against a panel of five
      pathogenic Tg peptides that contained iodine. CONCLUSIONS: The results suggest
      that development of ISAT in NOD.H2h4 mice is not associated with enhanced iodine
      organification or differential B- or T-cell responses to iodinated determinants
      in Tg.

PMID- 20687400
TI  - Low-dose metformin improves pregnancy rate in in vitro fertilization repeaters
      without polycystic ovary syndrome: prediction of effectiveness by multiple
      parameters related to insulin resistance.
AB  - OBJECTIVE: Insulin resistance is associated with aging and stress, both common
      among patients repeatedly failing to conceive with in vitro fertilization (IVF
      repeaters). In the present study we examined whether low-dose metformin could
      improve the outcome in IVF repeaters without polycystic ovary syndrome (PCOS).
      DESIGN: Study I was a preliminary clinical trial aiming at defining indications
      for therapy; study II was a prospective randomized study. The studies involved a
      university hospital and a private infertility clinic. We studied 232 women
      without PCOS who had failed at least twice to conceive by previous IVF. Metformin
      (500 mg/ day) was administered for 8 to 12 weeks before and during ovarian
      stimulation (metformin IVF). In study I, IVF outcomes with metformin (n = 33)
      were compared to outcomes without metformin of previous IVF in the same subjects.
      A discriminant score (DS) was determined from nine parameters assessed before
      metformin administration to predict achievement of ongoing pregnancy by metformin
      IVF. In study II (n = 199), ongoing pregnancy rates were compared prospectively
      between groups with/without metformin and with DS above/below 0.6647. RESULTS:
      Study I. Ongoing pregnancy rate improved significantly with metformin compared
      with previous IVF, and pregnancy correlated significantly with a DS at an optimal
      threshold of 0.6647 (sensitivity, 0.90; specificity, 0.91). Study II. Ongoing
      pregnancy and implantation rates were significantly higher in women with a DS
      above 0.6647 who received metformin (56% and 33%) compared with those having a DS
      below 0.6647 with metformin (14% and 11%) and those having a DS above/below
      0.6647 without metformin (20% and 7.1%/15% and 11%, respectively). CONCLUSIONS:
      Low-dose metformin improved pregnancy rate in IVF repeaters without PCOS,
      probably by decreasing insulin resistance. Indication can be determined from
      insulin-resistance-related multiple parameters assessed before metformin
      administration.

PMID- 20687401
TI  - Parental involvement does not augment the effectiveness of an intense behavioral
      program for the treatment of childhood obesity.
AB  - OBJECTIVE: To evaluate the effectiveness of active parental involvement in a
      lifestyle intervention for the management of childhood obesity. DESIGN: Forty-two
      overweight children (32 girls and 10 boys), aged 9.2 +/- 0.2 years and with
      percent overweight 39.8 +/- 2.7%, were randomly allocated either to a child-and
      parent group (N = 23) or a child-alone group (N = 19). Both groups attended a 3
      month multidisciplinary program extended by booster sessions during follow-up,
      which involved many cognitive behavioral therapy principles and assigned high
      self-regulation to the children, but differed in parental involvement. Percent
      overweight was evaluated at baseline, and at 3, 6, and 18 months thereafter.
      RESULTS: There was no significant interaction between time and group or a
      significant difference between groups. Percent overweight decreased by 4.9 +/-
      1.4 at 18 months (p < 0.001); the reduction occurred during the active phase of
      the treatment (0-3 months) and was maintained thereafter. CONCLUSION: In the
      setting of the present study, the active parental involvement did not
      significantly modify the results of lifestyle interventions for children's
      overweight management.

PMID- 20687402
TI  - Isolated idiopathic central hypothyroidism in an adult, possibly caused by
      thyrotropin releasing hormone (TRH) deficiency.
AB  - Central hypothyroidism (Central H) is mainly due to acquired lesions, either in
      the pituitary, the hypothalamus or both, and in such cases it is usually
      associated with deficient secretion of ther pituitary hormones. Isolated central
      hypothyroidism (I Central H) remains a very rare disease. By the use of the serum
      thyroid stimulating hormone (TSH) assay as an initial screening test for thyroid
      disease, the diagnosis of I, Central H can be missed or delayed, since most of
      these patients have normal or even slightly high serum TSH concentrations. We
      present a 54-year-old woman with intense tiredness, in whom hypothyroidism was
      initially and persistently excluded because of normal TSH levels. Further
      investigations showed again a normal TSH with slightly low free thyroxine (FT4),
      and Central H was suspected. A thyrotropin releasing hormone (TRH) stimulation
      test confirmed the diagnosis. No lesion was found by magnetic resonance imaging
      (MRI). No other pituitary hormone insufficiency was detected. Finally, after
      excluding, the intake of any drug affecting the hypothalamo-pituitary-thyroid
      axis and the presence of critical systemic illness, the unusual diagnosis of
      idiopathic isolated Central H was made. When suspecting Central H, both FT4 and
      TSH should be measured and if these values are low, TSH response to TRH is
      recommended to reach specific diagnosis.

PMID- 20687404
TI  - Precursor to kindness.

PMID- 20687403
TI  - Hypoglycaemia: possible mediation by chromium salt medication.

PMID- 20687405
TI  - Itty bitty boxes...and the big headaches they can bring.

PMID- 20687406
TI  - Put in her place. A dislocated patella and a plane to catch--can this be fixed in
      the field?

PMID- 20687407
TI  - Bryan Bledsoe, DO, FACEP. Keeping a wary eye; hands off hypertension. Interview
      by John Erich.

PMID- 20687408
TI  - PART 7: Accountability for ourselves and our colleagues.

PMID- 20687409
TI  - The spitting image of a heart attack.

PMID- 20687410
TI  - Collar me bad. Study prompts worries that cervical devices may harm some
      patients.

PMID- 20687411
TI  - Managing the acutely agitated patient. Why Denver brought back the forgotten
      agent droperidol.

PMID- 20687412
TI  - Beyond the box. Moving from protocols to treatment guidelines in British
      Columbia.

PMID- 20687413
TI  - As cool as us. How EMS can help drive the care patients get in hospitals.

PMID- 20687414
TI  - Hypothermia for SCI.

PMID- 20687415
TI  - The Resuscitation Academy: System leaders from around the world come to
      Seattle/King County to learn the secrets of the region's survival rates.

PMID- 20687416
TI  - Quality improvement. Part 1: retrospective review: EMS agencies must embrace
      continous quality improvement as part of their daily operation.

PMID- 20687417
TI  - Seizure control.

PMID- 20687418
TI  - Geriatric abuse.

PMID- 20687419
TI  - Medication considerations.
AB  - Because geriatric patients have a slowed metabolism and delayed ability to
      eliminate drugs from their body, they become more sensitive to drug doses and may
      benefit from decreased drug quantities at increased intervals. When administering
      drugs to pregnant women, remember that every drug you give them will also be
      given to their fetus. Refer to FDA drug categorization prior to administering any
      drug to pregnant women. If you are unsure, contact a physician prior to
      administration.

PMID- 20687420
TI  - Alphabetical disorder.

PMID- 20687421
TI  - [Physicians' administrative work is increasing more and more].

PMID- 20687422
TI  - [Fewer and fewer drownings among children--in Sweden and internationally. Global
      trend is connected to economical development and welfare].

PMID- 20687423
TI  - [Children with a single parent are a risk group for drowning. Also immigrant
      children from the Middle East and Iran are at risk according to a descriptive
      study].

PMID- 20687424
TI  - [Mortality statistics--a vital challenge. "Verbal autopsy" can help poor
      countries develop better health care].

PMID- 20687425
TI  - [Ghrelin--new promising treatment in anorexia and catabolic conditions].

PMID- 20687426
TI  - [Well-functioning strategy for the A/H1N1 pandemic in Varmland. A preliminary
      summary].

PMID- 20687427
TI  - [Physical activity in mental illness strongly recommended in new guidelines].

PMID- 20687428
TI  - [The cholesterol myth kept alive by artificial breathing].

PMID- 20687429
TI  - ["Who was calling "I" through my mouth?" Bertil Malmberg's poetry renewed by
      alcohol abuse and stroke].

PMID- 20687430
TI  - Lead in laboratory-fabricated dental restoration.

PMID- 20687431
TI  - Nerve injury following a mandibular block: a case report.

PMID- 20687432
TI  - Adjunctive periodontal therapy: a review of current techniques.
AB  - This paper has reviewed the different types of adjunctive therapeutic approaches
      used in the control of periodontitis. While there are many avenues of current
      clinical use and research, it is generally agreed that all of the modalities
      reviewed are adjunctive to basic mechanical control of the root surface
      environment in the form of SRP.

PMID- 20687433
TI  - Periodontal treatment of benign mucous membrane pemphigoid.

PMID- 20687434
TI  - The 30th anniversary of the triple tray! Interview by Damon Adams.

PMID- 20687435
TI  - Phase format treatment for endodontic therapy.
AB  - This paper has shown that modern endodontics has progressed significantly in
      describing and treating pulpal and periradicular pathology. Current knowledge
      indicates that endodontic therapy should be evaluated as a complete unit and that
      each phase of treatment is completed to provide a foundation for rehabilitation.
      The phase format assessment of endodontic therapy success provides an outline for
      clinicians to objectively provide treatment in effort to conserve natural
      dentition.

PMID- 20687436
TI  - Minimally invasive solutions for pediatric and adult patients.

PMID- 20687437
TI  - Denture stabilization with small-diameter implants.

PMID- 20687438
TI  - Doctor-technician teams connecting via the Internet.

PMID- 20687439
TI  - Aesthetic efficiency in a post-and-core system.

PMID- 20687440
TI  - Nanocomposites provide reliability and aesthetics.

PMID- 20687441
TI  - [A practical example of the application of the "Belgian geriatric evaluation and
      management program" within a general hospital].
AB  - A concrete realisation of the "Geriatric assessment and management program" as
      described in the arrete royal within a general hospital: definition of the
      geriatric patient, his detection, his follow-up and the transmission of patient
      information. The analysis of the first results indicates the importance of the
      biographic and socio-economics factors. The optimisation of an early screening
      and the communication between caregivers are key aspects to enhance the care of
      this patients.

PMID- 20687442
TI  - [Assessment of the spatial memory in patients suffering from generalized
      epilepsy].
AB  - This study aimed to assess eventual disturbances of spatial memory in patients
      suffering from generalized epilepsy in order to better grasp these patients'
      attitudes so as to keep track their neuropsychological accompaniments. 70
      patients presenting generalized epilepsy have taken part in spatial memory test.
      The test consists in studying the arrangement, the designation and the evocation
      of images in the course of spatial disposition learning test. Over the 70
      patients, 51% of the cases passed the test with performances similar to
      witnesses, 29% passed the test with late learning. Eventually 20% of patients
      failed to the test.

PMID- 20687443
TI  - [Cardiovascular disease prevention and health promotion in the French speaking
      community of Belgium].
AB  - Cardiovascular diseases remain the first cause of mortality in Belgium and are a
      priority for the Five-year program of health promotion in the French speaking
      Community. It is declined in operational programs by priority thematics,
      including the heart health. With this framework, it appeared necessary to
      operationalize cardiovascular priorities. A process of systemic and participative
      planning was set up in order to seek operational strategies and actions, and to
      cover the whole population and actors concerned with these health problems. The
      various cardiovascular risk factors, which potentiate one another, are approached
      together and in a global way. Upstream to the risk factors, social health
      determinants play an important role in cardiovascular diseases and others
      diseases like cancers. Tracking cardiovascular risk factors among people 30 to 75
      years is also proposed. It makes it possible to identify people at risk and to
      put forward individual and adapted measures. The plan integrates actions of
      health promotion (acting on the health determinants and factors which influence
      them) as well as actions aiming at improving tracking and the accompaniment of
      the patients in secondary and tertiary prevention. Actions on health determinants
      and the factors influencing them present moreover the advantage of being often
      common to many chronic diseases.

PMID- 20687444
TI  - [New data about lipoprotein(a): a curious molecule or a causal cardiovascular
      risk factor?].
AB  - Lipoprotein(a) is of interest to both basic researchers as well as to clinicians
      who are involved in the contribution of Lp(a) to cardiovascular risk profiles.
      The Lp(a) particle is a hybrid molecule consisting of a half part indistinguable
      from circulating LDL linked to the unique glycoprotein component
      apolipoprotein(a). Many epidemiological data indicate that elevated Lp(a) levels
      are an independent risk factor for vascular disease. Apo(a) is highly homologous
      to the fibrinolytic plasminogen containing many repeated kringle motifs similar
      to several of those found in the plasminogen molecule. The size of the kringle
      domain in apo(a) gives rise to Lp(a) isoforms heterogeneity which is a hallmark
      of this lipoprotein. The similarity between Lp(a) and plasminogen led to
      speculation of a bridging role for Lp(a) in atherosclerosis and thrombosis
      mechanisms based on the double structure of this lipoprotein. Moreover, there are
      specific properties that apo(a) confers to Lp(a) : this include the ability of
      Lp(a) to affect platelet function and to contribute to endothelial dysfunction.
      Recently, new data have revealed a potential role for Lp(a) in the elimination of
      oxidized phospholipids. Future areas of development in this field include the
      role of apo(a) isoform size as a risk factor, the possible physiological roles of
      Lp(a), as well as recommendations for the best treatment of elevated Lp(a) in
      clinical practice.

PMID- 20687445
TI  - [Coronary artery aneurysm associated with fistula: two anatomically similar cases
      with different clinical presentation].
AB  - Coronary artery fistulas are rare anomalies and their association with a coronary
      aneurysm even more infrequent. We report two cases which are illustrative because
      of their different clinical presentations. In the first case the diagnosis was
      made after discovering fortuitously a heart murmur. In contrast in the second
      case the coronary artery fistula was demonstrated during a check-up for thoracic
      pain. In both cases the right coronary artery gave a fistulous communication to
      the right atrium.

PMID- 20687446
TI  - [Meckel's diverticulum and obstruction of the small intestine in adult patients:
      report of two cases].
AB  - Meckel's Diverticulum (MD) is the most frequent congenital anomaly of the ileum.
      However, its clinical manifestations in adult patients are rare. In this paper,
      we report cases with two different mechanisms of small intestine obstruction due
      to MD and we discuss diagnosis and management of these symptomatic lesions in
      adult patients.

PMID- 20687447
TI  - [Blood coagulation disorder due to Vitamin K supplement: case report].

PMID- 20687448
TI  - [A Belgian medical board during World War II or the bad outcome of the law
      concerning the "Board of Medical Doctors " from 1938 (first part)].
AB  - The medical profession regulation has always been a delicate subject to deal
      with. The need for one arose as early as the 17th century. Multiple attempts to
      create such a regulation occurred during the 19th and the 20th century, which led
      to the 1938 "Board of Medical Doctors" law. This law could not be applied then
      because of the Second World War. After the Belgian capitulation of May 28th 1940,
      the Germans and some members of professional or political movements wished to
      create a Medical Board that was totally different from the one proposed by the
      1938 law. The background to this "33 Months Board" is analysed in this paper
      along with its functioning during the conflict. Among others this is based on the
      file dealing with the 1947 trial of this so called "Medical Board".

PMID- 20687449
TI  - [Do not resuscitate orders in the intensive care setting].
AB  - Even if Belgium (2002), The Netherlands (2002) and Luxemburg (2009) are the first
      three countries in the world to have legalized active euthanasia, there still is
      not a law on the do not resuscitate concept (NTBR or DNR). Nevertheless, numerous
      royal decrees and some consensus as well as advice given by the Belgian Medical
      Council, hold as jurisprudence. These rules remain amenable to change so as to
      suite the daily practice in intensive care units. This article describes the
      actual Belgian legal environment surrounding the intensive care specialist when
      he has to take such decisions.

PMID- 20687450
TI  - [Conflicts of interest: a concept often (voluntary) ignored by physicians].
AB  - A conflict of interest is a delicate situation where a person with a confidence
      role like a physician has professional or personal interests competing with the
      mission he/she has received, making him difficult to perform his/her duty with
      impartiality. Commercial or financial conflicts of interest of a physician can be
      personal and direct (gifts, travels, honoraries, consultant fees, etc.) or
      indirect (in relationship with those of the family or of the institution). There
      are also non financial conflicts of interest such as the anonymous peer review of
      the work performed by a friend or a competitor. An abundant literature mainly
      deals with the links to the pharmaceutical industry. Those links may lead to
      restrictions for publication and access to the data obtained by the research. The
      physicians have difficulties for accepting disclosing their conflict of interest.
      In this article, the literature published on the topic is reviewed as well as the
      main biases they can induce and the mistakes made by the physicians who do not
      declare their conflicts. Measures that can be taken to reduce their impact such
      as the declaration of conflicts of interest are discussed.

PMID- 20687451
TI  - Increased efficiency using the encapsulation-dehydration cryopreservation
      technique for Arabidopsis thaliana.
AB  - Arabidopsis thaliana shoot tips were successfully cryopreserved using
      encapsulation-dehydration cryopreservation methods. Between one and seven shoot
      tips were encapsulated within 4 mm calcium-alginate beads. Beads were formed in
      the presence of 2 M glycerol + 0.4 M sucrose. The time required to make 10 beads,
      each containing five shoot tips (4 min), was less than the time required to make
      50 beads containing one shoot tip (12 min). Shoot tip regrowth after cryoexposure
      was between 60 and 68%, with one to seven shoot tips per bead. Using five
      Arabidopsis shoot tips per bead, alginate beads were formed either in the
      presence of 2 M glycerol + 0.4 M sucrose or 0.5 M sucrose. Beads formed in the
      presence of glycerol were immediately air-dried to moisture contents between 0.21
      to 0.26 g H2O/g FW (0.27 to 0.38 g H2O/g DW). Alginate beads formed in 0.5 M
      sucrose were incubated in solutions of 0.5, 0.75, and 1 M sucrose for one day
      each prior to air-dehydration, achieving moisture contents of 0.19 to 0.21 g
      H2O/g FW (0.23 to 0.27 g H2O/g DW). Shoot tip regrowth after cryoexposure was
      between 42 and 65%, with no significant differences among treatments. We
      successfully reduced the amount of time needed for shoot tip processing for
      Arabidopsis by encapsulating five shoot tips per alginate bead and by using a
      glycerol-encapsulation method, without lowering shoot tip regrowth levels after
      cryopreservation.

PMID- 20687452
TI  - Cryoprotective effect of low-molecular-weight hyaluronan on human dermal
      fibroblast monolayers.
AB  - The purpose of this study was to assess the availability of low-molecular-weight
      (low-MW) hyaluronan (HA) as a cryoprotectant for cellular cryopreservation. To
      clarify whether low-MW HA is cryoprotective, we evaluated the effect of HA
      concentration (0-5% w/w) in a cryoprotectant solution on cell membrane integrity
      after freeze-thaw. A test sample was created using human dermal fibroblast
      monolayers incubated in a culture dish for 24 h (37 degrees C, 5% CO2). Sodium
      hyaluronate (MW 3 x 10(4)-5 x 10(4)) dissolved in medium served as the
      cryoprotectant solution. Samples were immersed in the solution for 2 h at 0-4
      degrees C. They were frozen at a cooling rate of 3 degrees C/min from 4 to -80
      degrees C, cooled further to below -185 degrees C, and then thawed. Cell membrane
      integrity after thawing was evaluated using a trypan blue exclusion assay. The
      sample and freezing procedures were repeated in subsequent experiments, while the
      conditions of the solution immersion with respect to the sample varied. Next, to
      clarify whether the cryoprotective action of HA is intra- or extracellular, we
      performed three experiments. The first studied the dependence of membrane
      integrity after freeze-thaw on preliminary incubation time (0.75-24 h at 37
      degrees C) with a sample immersed in the solution (5% w/w HA). In the second,
      membrane integrity of thawed samples that were initially frozen in a medium
      instead of solution, by removing extracellular HA following a preliminary 6-h
      incubation period, were evaluated. Thirdly, we investigated cellular uptake of
      fluorescein isothiocyanate-labeled HA (MW 10(5), 1% w/w) after a preliminary 6-h
      incubation period under fluorescent microscopy (without freeze-thaw). The results
      show that HA had a cryoprotective effect, and that this cryoprotective action was
      intracellular. Therefore, low- MW HA proves to be a promising cellular
      cryoprotectant.

PMID- 20687453
TI  - Cryopreservation of the human ovarian tissue induces the expression of Fas system
      in morphologically normal primordial follicles.
AB  - The aim of this study was to investigate whether the Fas system was involved in
      cryopreservation process of the human ovarian tissue. Human ovarian cortical
      tissues were cryopreserved using slow freezing method. Terminal deoxynucleotidyl
      transferase-mediated dUTP nick end labeling (TUNEL) was used to investigate
      apoptosis of primordial follicle. Fas, Fas ligand and active caspase-3 expression
      were detected by means of immunohistochemistry. The results showed that
      immunostaining for Fas, Fas ligand and active caspase-3 were not detected in
      morphologically normal primordial follicles in fresh ovarian tissue. After
      cryopreservation, Fas, Fas ligand and active caspase-3 immunostaining were
      present in morphologically normal primordial follicles. The study showed that
      cryopreservation of the human ovarian tissue induced the expression of Fas system
      in morphologically normal primordial follicles.

PMID- 20687454
TI  - Theoretical prediction of the effect of heat transfer parameters on cooling rates
      of liquid-filled plastic straws used for cryopreservation of spermatozoa.
AB  - Heat transfer plays a key role in cryopreservation of liquid semen in plastic
      straws. The effect of several parameters on the cooling rate of a liquid-filled
      polypropylene straw when plunged into liquid nitrogen was investigated using a
      theoretical model. The geometry of the straw containing the liquid was
      assimilated as two concentric finite cylinders of different materials: the fluid
      and the straw; the unsteady-state heat conduction equation for concentric
      cylinders was numerically solved. Parameters studied include external
      (convection) heat transfer coefficient (h), the thermal properties of straw
      manufacturing material and wall thickness. It was concluded that the single most
      important parameter affecting the cooling rate of a liquid column contained in a
      straw is the external heat transfer coefficient in LN2. Consequently, in order to
      attain maximum cooling rates, conditions have to be designed to obtain the
      highest possible heat transfer coefficient when the plastic straw is plunged in
      liquid nitrogen.

PMID- 20687455
TI  - Establishment and cryopreservation of a fibroblast cell line derived from Bengal
      tiger (Panthera tigris tigris).
AB  - The Bengal tiger ear marginal tissue fibroblasts cell line (BTF22), containing
      157 tubes of frozen cells, was successfully established by using primary explants
      technique and cell cryoconservation technology. Biological analysis showed that
      the population doubling time (PDT) for revival cells was approximately 28 h.
      Measurement of LDH and MDH isoenzymes showed no cross-contamination among the
      cells. Karyotyping showed that the frequency of cells with chromosome number 2n =
      38 was 90.6-92.2%. Tests for bacteria, fungi, viruses and mycoplasma were
      negative. Plasmids encoding the fluorescent proteins pEGFP-N3, pEGFP-C1, pECFP
      N1, pECFP-mito, pDsRed1-N1, and pEYFP-N1 were transfected into cells to study
      exogenous gene expression in the cells. The plasmid transfection efficiency was
      between 4.4% and 31.9%. Every index of the BTF22 cell line meets all the standard
      quality controls of American type Culture Collection (ATCC). Not only has the
      germline of this important Bengal tiger species been preserved at the cell level,
      but also valuable material had been provided for genome, postgenome and
      somacloning research. Moreover, the establishment of this technical platform
      would provide both technical and theoretical support for storing the genetic
      resources of other animals and poultry at the cell level.

PMID- 20687456
TI  - Cryopreservation of orthodox seeds of Alnus glutinosa.
AB  - We evaluated the sensitivity of orthodox seeds of black alder (Alnus glutinosa
      (L.) Gaertn.) to extreme desiccation and/or to the ultra-low temperature of
      liquid nitrogen (LN; -196 degrees C). The critical water content (WC) of
      desiccated seeds and the high-moisture freezing limit of seeds desiccated or
      imbibed to various WCs and frozen for 24 h or up to two years in LN was
      determined. Germination tests revealed that desiccation to 0.03 g H20.g(-1) dry
      mass was not detrimental to these seeds. Seeds tolerated LN freezing when the WC
      was 0.03-0.18 g H2O g(-1) dm (nuts). Seeds desiccated to this WC and stored in LN
      for two years showed similar germination as seeds stored at -3 degrees C for two
      years. Therefore, long-term cryopreservation of A. glutinosa seeds in genebanks
      is feasible.

PMID- 20687457
TI  - Loading trehalose into red blood cells by electroporation and its application in
      freeze-drying.
AB  - Freeze-drying is one potentially ideal method for long-term storage of red blood
      cells (RBCs). Intracellular trehalose is believed to be an effective protectant
      to stabilize cells during freezing and drying. In this study, we adopted
      electroporation to load trehalose into human RBCs first. The effects of
      electroporation parameters (extracellular trehalose concentration, field
      strength, pulse length and frequency) on loading efficiency were studied. The
      results show that RBCs can be loaded with 63.7 mM trehalose at 800 mM
      extracellular trehalose concentration, 1.5 kV/cm,field strength, 1 ms pulse
      length, 4 pulses in one minute. Then, RBCs loaded with different amount of
      trehalose by electroporation were freeze-dried and rehydrated. Recovery rates of
      trehalose-loaded and freeze-dried RBCs increased with intracellular trehalose
      concentration. The recovery rate of RBCs loaded with 63.7 mM trehalose reached
      70.9%. In conclusion, electroporation is an effective method for loading of
      nonpermeating trehalose into RBCs and therefore benefit freeze-drying of RBCs.

PMID- 20687458
TI  - Cryopreservation of organotypical cultures based on 3D scaffolds.
AB  - An integral component of the manufacture of a skin substitute is the
      cryopreservation of the complete skin construct. Under this demand,
      investigations were carried out in the present work in the case of
      cryopreservation of human fibroblasts and keratinocytes composed to organotypical
      skin substitutes (OTS). Two scaffolds made up of gelatine and collagen/elastin
      were seeded with human fibroblasts via centrifugation method. Subsequent human
      keratinocytes were applied on the preceded scaffolds and cultivated under air
      exposed conditions. For the investigation of the cryopreservation, OTS were
      frozen after 10 days cultivation via computer-controlled CryoMed included defined
      freezing conditions. After 24 hours storage in fluid nitrogen the OTSs were
      thawed and recultivated under airlift conditions. After that metabolic activity
      and immunfluorescent staining was analyzed in comparison with conventionally
      produced OTSs on basis of collagengel and/or OTSs based on scaffolds without
      cryopreservation. It could be assessed that cryopreservation has no negative
      influence on vitality and differentiation capacity of the cultivated constructs.
      The determination of OTS vitality after 14 days airlift culture delivered
      persistent higher metabolic activities of the scaffold based constructs in
      comparison with the corresponding controls. This could be confirmed by
      investigation of OTSs with and without cryopreservation. All expression patterns
      of differentiation marker could be detected after cryopreservation and subsequent
      recultivation. The results from cryopreservation of OTSs introduced here prove
      the possibility of temporally independent tailor-made applications by means of a
      complete skin substitute for example in the area pharmascreening.

PMID- 20687459
TI  - [Aspects of early MS treatment].

PMID- 20687460
TI  - [Roflumilast: a new approach to therapy of chronic obstructive pulmonary
      disease].
AB  - Roflumilast, a new inhibitor of phosphodiesterase 4, showed moderate efficacy in
      clinical trials with patients suffering from chonic obstructive pulmonary disease
      (COPD). Improvement of pulmonary function is predominantly attributed to
      antiinflammatory effects with decrease in mucus secretion and less exacerbations.
      Diarrhoea, headache and nausea are typical adverse events.

PMID- 20687461
TI  - [Pain therapy in proctology].
AB  - Pain in the anorectal region can be quite considerable. They can be treated
      effectively however. Before treatment the correct diagnosis is important. In each
      pain regimen it is important that patients have a normally sized stool (Bristol
      stool form scale type 4). Diclofenac (3 dd 50 mg) should be routinely used in
      anorectal pain. If diclofenac does not sufficiently relieve the pain, one should
      add metamizole or tramadole. Topically relaxing or analgetic agents (glyceryl
      trinitrate, botulinum toxin A, diltiazem, nifedipin, metronidazole, cincho- or
      lignocaine) might be used in selected cases. If edema exists topical steroids
      might have an analgetic effect.

PMID- 20687462
TI  - [Intestinal helminthiases].
AB  - Intestinal helminthiases are infections in which adult helminths (nematodes,
      trematodes, cestodes) parasitize the intestine. In Central Europe intestinal
      helminthiases are usually acquired during travel or are imported by migrants. In
      contrast, in developing countries, intestinal helminthiases are highly prevalent.
      The mode of transmission and the clinical picture depend on the helminth species.
      Special laboratory methods are needed to diagnose the different intestinal
      helminthiases. Nematodes are usually treated with the benzimidazoles mebendazole
      and albendazole. Ivermectin, a macrocyclic lactone, is an alternative.
      Praziquanel is the drug of choice for the treatment of intestinal cestodes.

PMID- 20687463
TI  - [Hepatitis A vaccination three days before departure to Eastern Europe?].
AB  - Vaccination against hepatitis A is indicated for travellers who visit areas with
      a high exposure to this type of virus. Beside tropical areas an active
      vaccination is indicated for the whole Mediterranean Area and Eastern Europe.
      This active vaccination is effective even short before departure due to the long
      incubation period of hepatitis A.

PMID- 20687464
TI  - The impact of healthcare reform on medical device companies.

PMID- 20687465
TI  - Polyploidization and cancer. Preface.

PMID- 20687466
TI  - Polyploidy, aneuploidy and the evolution of cancer.
AB  - Aneuploidy is a ubiquitous feature of cancer and pre-cancerous lesions, yet its
      significance is poorly characterized. In this chapter, we review the role
      oftetraploidy and aneuploidy in progression. We examine how aneuploidy may
      contribute to the evolutionary dynamics prevalent in neoplastic progression,
      considering whether aneuploidy itself is selectively neutral or advantageous or
      if it simply acts as a mechanism for the more rapid accumulation of mutations
      increasing survival and reproduction of cancer cells. We also review evidence
      from Barrett's esophagus, a pre-malignant condition, demonstrating that
      tetraploidy and aneuploidy are correlated with an increased risk of progression
      to cancer. Ultimately, we aim provide testable hypotheses and methods for
      understanding the role of aneuploidy in cancer.

PMID- 20687467
TI  - Molecular mechanisms and function of the spindle checkpoint, a guardian of the
      chromosome stability.
AB  - For equal segregation, chromosomes, which are distributed randomly in the nucleus
      of interphase, must be aligned at the spindle equator in mitosis before the onset
      of sister chromatid separation. The spindle checkpoint is a surveillance
      mechanism that delays the onset of sister chromatid separation while each
      chromosome is on the way to the spindle equator. Failure in the function of the
      checkpoint results in aneuploidy/polyploidy, which would be a cause of cancer.
      Here, we review chromosome dynamics in mitosis, molecular mechanisms of the
      spindle checkpoint and finally tumorigenesis triggered by missegregation of
      chromosomes.

PMID- 20687469
TI  - DNA damage and polyploidization.
AB  - A growing body of evidence indicates that polyploidization triggers chromosomal
      instability and contributes to tumorigenesis. DNA damage is increasingly being
      recognized for its roles in promoting polyploidization. Although elegant
      mechanisms known as the DNA damage checkpoints are responsible for halting the
      cell cycle after DNA damage, agents that uncouple the checkpoints can induce
      unscheduled entry into mitosis. Likewise, defects of the checkpoints in several
      disorders permit mitotic entry even in the presence of DNA damage. Forcing cells
      with damaged DNA into mitosis causes severe chromosome segregation defects,
      including lagging chromosomes, chromosomal fragments and chromosomal bridges. The
      presence of these lesions in the cleavage plane is believed to abort cytokinesis.
      It is postulated that if cytokinesis failure is coupled with defects of the p53
      dependent postmitotic checkpoint pathway, cells can enter S phase and become
      polyploids. Progress in the past several years has unraveled some of the
      underlying principles of these pathways and underscored the important role of DNA
      damage in polyploidization. Furthermore, polyploidization per se may also be an
      important determinant of sensitivity to DNA damage, thereby may offer an
      opportunity for novel therapies.

PMID- 20687470
TI  - Role of the p53 family in stabilizing the genome and preventing polyploidization.
AB  - Cellular defects resulting in chromosomal instability and aneuploidy are the most
      common features of human cancers. As a major tumor suppressor and intrinsic part
      of several cellular checkpoints, p53 contributes to maintenance of the stability
      of the genetic material, both in quality (ensures faithful replication) and
      quantity (preservation of diploidy). Although the exact trigger of p53 in case of
      numerical chromosomal aberrations is unknown, the absence of p53 allows polyploid
      cells to proliferate and generate unstable aneuploid progeny. A more recent
      addition to the p53 family, p73, emerged as an important contributor to genomic
      integrity when p53 is inactivated. p73 loss in p53-null background leads to a
      rapid increase in polyploidy and aneuploidy, markedly exceeding that caused by
      p53 loss alone. Constitutive deregulation of Cyclin-Cdk and p27/Kip1 activities
      and excess failure of the G2/M DNA damage checkpoint are important deficiencies
      associated with p73 loss.

PMID- 20687471
TI  - Centrosomes, polyploidy and cancer.
AB  - Cancer cells are frequently characterized by ploidy changes including tetra-,
      poly- or aneuploidy. At the same time, malignant cells often contain
      supernumerary centrosomes. Aneuploidy and centrosome alterations are both
      hallmarks of tumor aggressiveness and increase with malignant progression. It has
      been proposed that aneuploidy results from a sequence of events in which failed
      mitoses produce tetra-/polyploid cells that enter a subsequent cell division with
      an increased number of centrosomes and hence with an increased risk for
      multipolar spindle formation and chromosome missegregation. Although this model
      attempts to integrate several common findings in cancer cells, it has been
      difficult to prove. Findings that centrosome aberrations can arise in diploid
      cells and the uncertain proliferative potential of polyploid cells suggest that
      alternative routes to chromosomal instability may exist. We discuss here recent
      results on centrosome biogenesis and the possible link between ploidy changes,
      centrosome aberrations and cancer.

PMID- 20687472
TI  - Polyploidy: mechanisms and cancer promotion in hematopoietic and other cells.
AB  - Polyploidy, the state of having greater than a diploid content of DNA (e.g.,
      tetraploid, octaploid, etc) has been recognized in a large variety of both, plant
      and animal cells. Human and murine megakaryocytes, hepatocytes, arterial smooth
      muscle cells and cardiac myocytes, all develop a certain degree of polyploidy
      during their normal lifespan. In addition, polyploid cells may be found in some
      tissues under conditions of stress, including uterine smooth muscle during
      pregnancy, aortic vascular smooth muscle cells during aging and hypertension,
      beta-cells in diabetic human or mouse thyroid cells in hyperthyroidism and cells
      in seminal vesicles with aging. Polyploid cells are also found in malignant
      tissues in which they are believed to contribute to the development of cells with
      intermediate DNA content values (e.g., 3n, 4.5n, etc.). With the use of micro
      array, researchers have demonstrated that genetically identical yeast strains
      (Saccharomyces cerevisiae) with differences only in ploidy status (from haploid
      to tetraploid) display a substantial difference in gene expression, including of
      the G1 cyclins. This finding has suggested that DNA content per se might affect
      cellular functions.

PMID- 20687473
TI  - Polyploidization of liver cells.
AB  - Eukaryotic organisms usually contain a diploid complement of chromosomes.
      However, there are a number of exceptions. Organisms containing an increase in
      DNA content by whole number multiples of the entire set of chromosomes are
      defined as polyploid. Cells that contain more than two sets of chromosomes were
      first observed in plants about a century ago and it is now recognized that
      polyploidy cells form in many eukaryotes under a wide variety of circumstance.
      Although it is less common in mammals, some tissues, including the liver, show a
      high percentage of polyploid cells. Thus, during postnatal growth, the liver
      parenchyma undergoes dramatic changes characterized by gradual polyploidization
      during which hepatocytes of several ploidy classes emerge as a result of modified
      cell-division cycles. This process generates the successive appearance of
      tetraploid and octoploid cell classes with one or two nuclei (mononucleated or
      binucleated). Liver cells polyploidy is generally considered to indicate terminal
      differentiation and senescence and to lead both to the progressive loss of cell
      pluripotency and a markedly decreased replication capacity. In adults, liver
      polyploidization is differentially regulated upon loss of liver mass and liver
      damage. Interestingly, partial hepatectomy induces marked cell proliferation
      followed by an increase in liver ploidy. In contrast, during hepatocarcinoma
      (HCC), growth shifts to a nonpolyploidizing pattern and expansion of the diploid
      hepatocytes population is observed in neoplastic nodules. Here we review the
      current state of understanding about how polyploidization is regulated during
      normal and pathological liver growth and detail by which mechanisms hepatocytes
      become polyploid.

PMID- 20687468
TI  - Understanding cytokinesis failure.
AB  - Cytokinesis is the final step in cell division. The process begins during
      chromosome segregation, when the ingressing cleavage furrow begins to partition
      the cytoplasm between the nascent daughter cells. The process is not completed
      until much later, however, when the final cytoplasmic bridge connecting the two
      daughter cells is severed. Cytokinesis is a highly ordered process, requiring an
      intricate interplay between cytoskeletal, chromosomal and cell cycle regulatory
      pathways. A surprisingly broad range of additional cellular processes are also
      important for cytokinesis, including protein and membrane trafficking, lipid
      metabolism, protein synthesis and signaling pathways. As a highly regulated,
      complex process, it is not surprising that cytokinesis can sometimes fail.
      Cytokinesis failure leads to both centrosome amplification and production of
      tetraploid cells, which may set the stage for the development of tumor cells.
      However, tetraploid cells are abundant components of some normal tissues
      including liver and heart, indicating that cytokinesis is physiologically
      regulated. In this chapter, we summarize our current understanding of the
      mechanisms of cytokinesis, emphasizing steps in the pathway that may be regulated
      or prone to failure. Our discussion emphasizes findings in vertebrate cells
      although we have attempted to highlight important contributions from other model
      systems.

PMID- 20687474
TI  - Analysis of cellular DNA content by flow and laser scanning cytometry.
AB  - This chapter covers several aspects of methodology of DNA content analysis in
      individual cells that is most commonly used for assessment of DNA ploidy and for
      enumeration of cells in particular phases of the cell cycle. Briefly presented
      are general principles of instrumentation and cell analysis by flow- and laser
      scanning- cytometry. Described are major methods designed to stain DNA with
      fluorochromes in live cells, in detergent-permeabilized cells, in cells fixed
      prior to DNA staining as well as in nuclei of cells isolated from paraffin
      embedded tissues. Briefly addressed are approaches to estimate cellular DNA
      content in conjunction with cellular immunophenotype. Discussed are factors that
      affect accuracy of DNA content measurement such as: (i) differences in chromatin
      structure of the analyzed cells that restrict DNA accessibility to fluorochromes,
      (ii) stoichiometry of interaction between fluorochromes and DNA in chromatin and
      (iii) chemical mass action law defining dependency of fluorochrome binding to DNA
      in relation to fluorochrome concentration and number of potential binding sites
      in a sample. Described also are controls used to ensure accuracy of DNA ploidy
      determination, the principles in ploidy assessment and possible pitfalls in
      analysis.

PMID- 20687475
TI  - Proteins: membrane binding and pore formation. Preface.

PMID- 20687476
TI  - Proteins: membrane binding and pore formation. Introduction.
AB  - Pore-forming proteins (PFPs) possess the intriguing property that they can exist
      either in a stable water-soluble state or as an integral membrane pore. These
      molecules can undergo large conformational changes in converting between these
      two states. Much of what we know about how these proteins change their shape
      comes from work on bacterial toxins and increasingly, in more recent years, on
      toxins from other organisms. Surprisingly, a number of pore-forming proteins have
      recently been characterised that appear to have adopted similar stratagies to
      toxins for binding and inserting into biological membranes.

PMID- 20687477
TI  - Energetics of peptide and protein binding to lipid membranes.
AB  - In every living cell, the lipid bilayer membrane is the ultimate boundary between
      the contents of the cell and the rest of universe. A single breach in this
      critical barrier is lethal. For this reason, the bilayer's permeability barrier
      is the point of attack of many offensive and defensive molecules, including
      peptides and proteins. Depending on one's perspective, these pore-forming
      molecules might be called toxins, venoms, antibiotics or host defense molecules
      and they can function by many different mechanisms, but they share one feature in
      common: they must bind to membranes to exert their effects. The thermodynamic and
      structural principles of polypeptide-membrane interactions are described in this
      chapter.

PMID- 20687478
TI  - Membrane association and pore formation by alpha-helical peptides.
AB  - Membrane-active peptides exhibit antimicrobial, channel-forming and transport
      activities and have therefore early on been interesting targets for biophysical
      investigations. When the peptide-lipid interactions are studied a dynamic view
      emerges in which the peptides change conformation upon membrane insertion, can
      adopt a variety of topologies and change the macroscopic phase properties of the
      membrane locally or globally. Interestingly several proteins have been identified
      that also interact with the membrane in a dynamic fashion and where the lessons
      learned from peptides may add to our understanding of the ways these proteins
      function.

PMID- 20687479
TI  - Role of membrane lipids for the activity of pore forming peptides and proteins.
AB  - Bilayer lipids, far from being passive elements, have multiple roles in
      polypeptide-dependent pore formation. Lipids participate at all stages of the
      formation of pores by providing the binding site for proteins and peptides,
      conditioning their active structure and modulating the molecular reorganization
      of the membrane complex. Such general functions of lipids superimpose to other
      particular roles, from electrostatic and curvature effects to more specific
      actions in cases like cholesterol, sphingolipids or cardiolipin. Pores are
      natural phenomena in lipid membranes. Driven by membrane fluctuations and packing
      defects, transient water pores are related to spontaneous lipid flip-flop and non
      assisted ion permeation. In the absence ofproteins or peptides, these are rare
      short living events, with properties dependent on the lipid composition of the
      membrane. Their frequency increases under conditions of internal membrane
      disturbance of the lipid packing, like in the presence of membrane-bound proteins
      or peptides. These latter molecules, in fact, form dynamic supramolecular
      assemblies together with the lipids and transmembrane pores are one of the
      possible structures of the complex. Active peptides and proteins can thus be
      considered inducers or enhancers of pores which increase their probability and
      lifetime by modifying the thermodynamic membrane balance. This includes
      destabilizing the membrane lamellar structure, lowering the activation energy for
      pore formation and stabilizing the open pore structure.

PMID- 20687480
TI  - Cholesterol-dependent cytolysins.
AB  - The cholesterol-dependent cytolysins (CDCs) are part of a large family of pore
      forming proteins that include the human proteins perforin and the complement
      membrane attack complex. The activity of all family members is focused on
      membranes, but the proteins are themselves involved in a diverse range of
      phenomena. An overview of some of these phenomena is provided here, along with an
      historical perspective of CDCs themselves and how our understanding of their
      mechanism of action has developed over the years. The way in which pore formation
      depends on specific characteristics of the membrane under attack as well as of
      the protein doing the attacking is emphasised. The cholesterol-dependent
      cytolysins (CDCs) have been the focus of a renewed keen research interest for
      over ten years now. Their importance has been even further enhanced by the
      homology now identified between them and the membrane attack complex/perforin
      (MACPF) family of proteins, which includes several components of the complement
      cascade as well as perforin itself. In this chapter I aim to provide an overview
      of our understanding of the interaction between CDCs and other members of what is
      now called the MACPF/CDC superfamily, with their target membranes. CDCs (also in
      the past known as thiol-activated toxins or cholesterol-binding toxins) were
      originally identified from four Gram-positive bacterial genera (Clostridium,
      Listeria, Bacillus and Streptococcus). Well-known examples include listeriolysin,
      perfringolysin, streptolysin and pneumoysin. Listeriolysin from L. monocytogenes
      is responsible for the escape of bacteria from the phagosome to colonise the
      cytoplasm and has been applied as a protein adjuvant in the development of
      vaccines against cancer and tuberculosis, for example. Perfringolysin from C.
      perfringens (Fig. 1A) has become perhaps the most studied CDC4 and has an
      important role in pathology associated with infection (gangrene). Streptolysin
      from S. pyogenes is another intensely studied CDC and has been applied widely in
      experimental permeabilisation of biological membranes. Pneumolysin is a major
      virulence determinant for S. pneumoniae, allowing bacterial invasion of tissues
      and mediating inflammation and the activation of the complement cascade. However,
      CDCs have now, for example, been identified in the bacteria Arcanobacterium
      pyogenes and Gardnerella vaginalis and there also appear to be homologues outside
      prokaryotes such as the sea anemone Metridium senile pore-forming toxin
      metridiolysin. The homology with the MACPF family was unknown until the first
      structures of the canonical fold of that family were solved, revealing the now
      characteristic MACPF/CDC fold of a twisted 3-sheet around which helices are
      clustered (Fig. 1A and D). Without any significant other sequence homology, the
      fold of this superfamily of pore-forming and membrane-binding proteins has been
      conserved by compensatory mutation around a handful of key conserved glycines.
      The glycines presumably act as critical hinges during the dramatic refolding that
      CDCs are known to undergo and which is presumably the selective advantage of this
      specific structure that has caused it to be conserved over such a vast
      evolutionary timescale. While not all MACPF domains are involved in pore
      formation-for example, C6 and C8beta--they are all apparently involved in action
      on membranes. The dramatic refolding undergone by CDCs is tightly coupled to
      their oligomerisation and results in the conversion of the helices hemming the
      core 3-sheet of the MACPF/CDC domain into a pair of beta-hairpins which in tandem
      and alongside those from other subunits within the oligomer insert into the
      membrane to create a pore (Fig. 1A-C). It is obviously the basic assumption that
      where nonCDC members of the superfamily-such as complement proteins and perforin
      act on membranes they do so by a mechanism involving similar refolding.58 Even
      where a member of the MACPF/CDC superfamily is not known to form a pore, or has
      been shown not to-at least alone-the same conformational change could have other
      adaptive functions during activity on or at membranes. However, the bicomponent
      nature of some pore-forming toxins alerts us that showing an absence of activity
      for one pure protein does not mean that they do not contribute to pore formation
      quite directly, since that may require the presence of another MACPF/CDC family
      member or members from the same specific system. Complement acts by a combination
      of the C5b-8 complex of proteins preassembled on a target membrane recruiting C9
      to form a lesion, which may be a complete ring of C9 associated with the C5b-8 or
      an arc-electron microscopy images show both possibilities.Perforin acts in
      concert with granzymes, to trigger apoptosis when delivered by cytotoxic cells at
      their targets (damaged, transformed and infected host cells). Incomplete rings
      are visible for perforin also and there are many unresolved issues concerning its
      mechanism and the dependence ofgranzymes on it for their delivery.

PMID- 20687481
TI  - Laetiporus sulphureus lectin and aerolysin protein family.
AB  - The parasitic mushroom Laetiporus sulphureus produces a family of lectins (LSL's)
      sharing 80-90% sequence identity that possesses a low but significant sequence
      similarity to the bacterial pore-forming toxins mosquitocidal toxin Mtx-2 from
      Bacillus sphaericus and a toxin from Clostridium septicum. The crystal structure
      of one member of the L. sulphureus lectins family (LSLa) reveals unexpected
      structural similarities to the 1-pore-forming toxins from the aerolysin family,
      namely, aerolysin from the Gram-negative bacterium Aeromonas hydrophila, epsilon
      toxin from Clostridium perfringens and parasporin from B. thuringiensis. This
      similarity presumably indicates that the hemolytic activity of LSLa proceeds
      through a molecular mechanism that involves the formation of oligomeric
      transmembrane beta-barrels. Comparison of the crystal structures of the above
      mentioned proteins reveals common pore-forming modules, which are then
      distributed both in bacteria and fungi. Currently, it can be stated that the
      above three dimensional structures have been key in revealing structural
      similarities that were elusive at the sequence level. A potential corollary from
      this is that structural studies aimed at determining high resolution structures
      of aerolysin-like pore-forming toxins, whose biological activity involves large
      conformational changes, are mandatory to define protein domains or structural
      motifs with membrane-binding properties.

PMID- 20687482
TI  - Interfacial interactions of pore-forming colicins.
AB  - Colicins are water soluble toxins secreted by E. coli cells to kill other E. coli
      and related species. To do this they need to cross the outer membrane, periplasm
      and inner membrane. Pore forming colicins, as their name suggests form a voltage
      dependent pore in the inner membrane. This chapter deals with the interfaces,
      both lipid and protein, that the colicins experience as they make the short but
      complex journey that brings them to the point of pore formation. The succession
      of molecular interactions with lipid and protein receptors causes a series of
      conformational changes which allow these large > 40 kDa proteins to outwit the
      normally tight defensive shield of the target cell. This is done by combining
      general physico-chemical interfacial interactions, such as the use of amphipathic
      helical peptides, with precisely targeted protein-protein interactions involving
      both rigid and natively disordered protein domains.

PMID- 20687483
TI  - Permeabilization of the outer mitochondrial membrane by Bcl-2 proteins.
AB  - The proteins of the Bcl-2 family regulate the release of the apoptotic factors
      from mitochondria during apoptosis, a key event in physiological cell death.
      Although their molecular mechanisms remain unclear, the Bcl-2 proteins have been
      proposed to directly control the permeability of the outer mitochondrial membrane
      by pore formation. Indeed, they share structural features with the pore forming
      domains of some bacterial toxins and they can give rise to proteolipidic pores in
      model membranes. The complex level of regulation needed to decide the fate of the
      cell is achieved by an intricate interaction network between different members of
      the family. Current models consider multiple parallel equilibria of activation
      and inhibition that determine whether the permeabilization of the mitochondrial
      outer membrane is induced or not.

PMID- 20687484
TI  - Molecular mechanism of sphingomyelin-specific membrane binding and pore formation
      by actinoporins.
AB  - Actinoporins are potent pore-forming toxins produced by sea anemones. They
      readily form pores in membranes that contain sphingomyelin. Molecular mechanism
      of pore formation involves recognition of membrane sphingomyelin, firm binding to
      the membrane accompanied by the transfer of the N-terminal region to the lipid
      water interface and oligomerization of three to four monomers with accompanying
      pore formation. Actinoporins are an important example of alpha-helical pore
      forming toxins, since the final conductive pathway is formed by amphipathic alpha
      helices. Recent structural data indicates that actinoporins are not restricted to
      sea anemones, but are present also in other organisms. They are becoming an
      important tool and model system, due to their potency, specificity and similarity
      to other proteins.

PMID- 20687485
TI  - Hemolysin E (HlyE, ClyA, SheA) and related toxins.
AB  - Certain strains of Escherichia coli, Salmonella enterica and Shigella flexneri
      produce a pore-forming toxin hemolysin E (HlyE), also known as cytolysin A (ClyA)
      and silent hemolysin, locus A (SheA). HlyE lyses erythrocytes and mammalian
      cells, forming transmembrane pores with a minimum internal diameter of-25 A. We
      review the current knowledge of HlyE structure and function in its solution and
      pore forms, models for membrane insertion, its potential use in biotechnology
      applications and its relationship to a wider superfamily of toxins.

PMID- 20687486
TI  - Pore formation by Cry toxins.
AB  - Bacillus thuringiensis (Bt) bacteria produce insecticidal Cry and Cyt proteins
      used in the biological control of different insect pests. In this review, we will
      focus on the 3d-Cry toxins that represent the biggest group of Cry proteins and
      also on Cyt toxins. The 3d-Cry toxins are pore-forming toxins that induce cell
      death by forming ionic pores into the membrane of the midgut epithelial cells in
      their target insect. The initial steps in the mode of action include ingestion of
      the protoxin, activation by midgut proteases to produce the toxin fragment and
      the interaction with the primary cadherin receptor. The interaction of the
      monomeric CrylA toxin with the cadherin receptor promotes an extra proteolytic
      cleavage, where helix alpha-1 of domain I is eliminated and the toxin
      oligomerization is induced, forming a structure of 250 kDa. The oligomeric
      structure binds to a secondary receptor, aminopeptidase N or alkaline
      phosphatase. The secondary receptor drives the toxin into detergent resistant
      membrane microdomains formingpores that cause osmotic shock, burst of the midgut
      cells and insect death. Regarding to Cyt toxins, these proteins have a
      synergistic effect on the toxicity of some Cry toxins. Cyt proteins are also
      proteolytic activated in the midgut lumen of their target, they bind to some
      phospholipids present in the mosquito midgut cells. The proposed mechanism of
      synergism between Cry and Cyt toxins is that Cyt1Aa function as a receptor for
      Cry toxins. The Cyt1A inserts into midgut epithelium membrane and exposes protein
      regions that are recognized by Cry11Aa. It was demonstrated that this interaction
      facilitates the oligomerization of Cry11Aa and also its pore formation activity.

PMID- 20687487
TI  - Role of heparan sulfates and glycosphingolipids in the pore formation of basic
      polypeptides of cobra cardiotoxin.
AB  - Cobra venom contains cardiotoxins (CTXs) that induce tissue necrosis and systolic
      heart arrest in bitten victims. CTX-induced membrane pore formation is one of the
      major mechanisms responsible for the venom's designated cytotoxicity. This
      chapter examines how glycoconjugates such as heparan sulfates (HS) and
      glycosphingolipids, located respectively in the extracellular matrix and lipid
      bilayers of the cell membranes, facilitate CTX pore formation. Evidences for HS
      facilitated cell surface retention and glycosphingolipid-facilitated membrane
      bilayer insertion of CTX are reviewed. We suggest that similar physical steps
      could play a role in the mediation of other pore forming toxins (PFT). The
      membrane pores formed by PFT are expected to have limited lifetime on biological
      cell surface as a result of membrane dynamics during endocytosis and/or
      rearrangement of lipid rafts.

PMID- 20687488
TI  - Amyloid peptide pores and the beta sheet conformation.
AB  - Over 20 clinical syndromes have been described as amyloid diseases.
      Pathologically, these illnesses are characterized by the deposition in various
      tissues of amorphous, Congo red stainingdeposits, referred to as amyloid. Under
      polarizing light microscopy, these deposits exhibit characteristic green
      birefringence. X-ray diffraction reveals cross-beta structure of extended amyloid
      fibrils. Although there is always a major protein in amyloid deposits, the
      predominant protein differs in each ofthe clinical syndromes. All the proteins
      exhibit the characteristic nonnative beta-sheet state. These proteins aggregate
      spontaneously into extended fibrils and precipitate out of solution. At least a
      dozen of these peptides have been demonstrated to be capable of channel formation
      in lipid bilayers and it has been proposed that this represents a pathogenic
      mechanism. Remarkably, the channels formed by these various peptides exhibit a
      number of common properties including irreversible, spontaneous insertion into
      membranes, production oflarge, heterogeneous single-channel conductances,
      relatively poor ion selectivity, inhibition of channel formation by Congo red and
      related dyes and blockade of inserted channels by zinc. In vivo amyloid peptides
      have been shown to disrupt intracellular calcium regulation, plasma membrane
      potential, mitochondrial membrane potential and function and long-term
      potentiation in neurons. Amyloid peptides also cause cytotoxicity. Formation of
      the beta sheet conformation from native protein structures can be induced by high
      protein concentrations, metal binding, acidic pH, amino acid mutation and
      interaction with lipid membranes. Most amyloid peptides interact strongly with
      membranes and this interaction is enhanced by conditions which favor beta-sheet
      formation. Formation of pores in these illnesses appears to be a spontaneous
      process and available evidence suggests several steps are critical. First,
      destabilization of the native structure and formation of the beta-sheet
      conformation must occur. This may occur in solution or may be facilitated by
      contact with lipid membranes. Oligomerization of the amyloid protein is then
      mediated by the beta strands. Amyloid monomers and extended fibrils appear to
      have little potential for toxicity whereas there is much evidence implicating
      amyloid oligomers of intermediate size in the pathogenesis of amyloid disease.
      Insertion of the oligomer appears to take place spontaneously although there may
      be a contribution of acidic pH and/or membrane potential. Very little is known
      about the structure of amyloid pores, but given that the amyloid peptides must
      acquire beta-sheet conformation to aggregate and polymerize, it has been
      hypothesized that amyloid pores may in fact be beta-sheet barrels similar to the
      pores formed by alpha-latrotoxin, Staphylococcal alpha-hemolysin, anthrax toxin
      and clostridial perfringolysin.

PMID- 20687489
TI  - Diseases of DNA repair. Preface.

PMID- 20687490
TI  - Triple-A syndrome.
AB  - Triple-A syndrome is characterized by triad of adrenocorticotrophic hormone
      (ACTH)-resistant adrenal insufficiency, alacrimia and achalasia cardia. It is a
      rare disease and inherited by autosomal recessive pattern. Allgrove syndrome is
      characterized by mutation(s) in AAAS gene, located on chromosome 12q13, that
      codes for ALADIN protein. Most mutations produce a truncated protein, although
      missense and point-mutations have also been reported. Some patients with Triple-A
      syndrome may not have mutations in AAAS gene; in those there is no specific
      genotype-phenotype correlation. Although alacrimia is not the usual presenting
      manifestation, probably it is the earliest and most consistent feature. Achalasia
      cardia and adrenal insufficiency are the early and usual presenting
      manifestations. Neurological features appear at later age and autonomic
      manifestations are the most common neurological disorder. Polyneuropathy,
      amyotrophy, optic atrophy are the other common neurological problems. Alacrimia
      is diagnosed by Schirmer's test while ahalasia cardia and adrenal insufficiency
      are best diagnosed by esophageal monometry and ACTH stimulated cortisol levels
      respectively. Alacrimia is treated with artificial tears while achalasia cardia
      with either pneumatic dilatation or Heller's myotomy. Adrenal insufficiency is
      treated with glucocorticoid and if necessary mineralocorticoid replacement.

PMID- 20687491
TI  - Amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a common neurological disorder that
      results in loss of motor neurons, leading to a rapidly progressive form of muscle
      paralysis that is fatal. There is no available cure and current therapies only
      provide minimal benefit at best. The disease is predominantly sporadic and until
      very recently only the Cu,Zn superoxide dismutase (Cu,ZnSOD), which is involved
      in a small number of sporadic cases and a larger component of familial ones, have
      been analyzed in any detail. Here we describe the clinical aspects of ALS and
      highlight the genetics and molecular mechanisms behind the disease. We discuss
      the current understanding and controversies of how mutations in Cu,ZnSOD may
      cause the disease. We also focus on the recent discovery that mutations in either
      TDP-43 or FUS/TLS, which are both involved in DNA/RNA synthesis, are likely the
      cause behind many cases of ALS that are not linked to Cu,ZnSOD.

PMID- 20687492
TI  - Early-onset ataxia with ocular motor apraxia and hypoalbuminemia/ataxia with
      oculomotor apraxia 1.
AB  - DNA single-strand breaks (SSBs) are non-overlapping discontinuities in strands
      ofa DNA duplex. Significant attention has been given on the DNA SSB repair (SSBR)
      system in neurons, because the impairment of the SSBR causes human
      neurodegenerative disorders, including early-onset ataxia with ocular motor
      apraxia and hypoalbuminemia (EAOH), also known as ataxia-oculomotor apraxia Type
      1 (AOA1). EAOH/AOA1 is characterized by early-onset slowly progressive ataxia,
      ocular motor apraxia, peripheral neuropathy and hypoalbuminemia.
      Neuropathological examination reveals severe loss of Purkinje cells and moderate
      neuronal loss in the anterior horn and dorsal root ganglia. EAOH/AOA1 is caused
      by the mutation in the APTX gene encoding the aprataxin (APTX) protein. APTX
      interacts with X-ray repair cross-complementing group 1 protein, which is a
      scaffold protein in SSBR. In addition, APTX-defective cells show increased
      sensitivity to genotoxic agents, which result in SSBs. These results indicate an
      important role ofAPTX in SSBR. SSBs are usually accompanied by modified or
      damaged 5'- and 3'-ends at the break site. Because these modified or damaged ends
      are not suitable for DNA ligation, they need to be restored to conventional ends
      prior to subsequent repair processes. APTX restores the 5'-adenylate
      monophosphate, 3'-phosphates and 3'-phosphoglycolate ends. The loss of function
      of APTX results in the accumulation of SSBs, consequently leading to neuronal
      cell dysfunction and death.

PMID- 20687493
TI  - Clinical features and pathogenesis of Alzheimer's disease: involvement of
      mitochondria and mitochondrial DNA.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder which results in the
      irreversible loss of cortical neurons, particularly in the associative neocortex
      and hippocampus. AD is the most common form of dementia in the elderly people.
      Apart from the neuronal loss, the pathological hallmarks are extracellular senile
      plaques containing the peptide beta-amyloid (AP) and neurofibrillary tangles. The
      Af cascade hypothesis remains the main pathogenetic model, as suggested by
      familiar AD, mainly associated to mutation in amyloid precursor protein and
      presenilin genes. The remaining 95% of AD patients are mostly sporadic late-onset
      cases, with a complex aetiology due to interactions between environmental
      conditions and genetic features of the individual. Mitochondria play a central
      role in the bioenergetics of the cell and apoptotic cell death. Morphological,
      biochemical and genetic abnormalities of the mitochondria in several AD tissues
      have been reported. Impaired mitochondrial respiration, particularly COX
      deficiency, has been observed in brain, platelets and fibroblasts of AD patients.
      Somatic mutations in mitochondrial DNA (mtDNA) could cause energy failure and
      increased oxidative stress. No causative mutations in the mtDNA have been
      detected and studies on mtDNA polymorphisms are controversial, but the
      "mitochondrial cascade hypothesis" here revised, could explain many of the
      biochemical, genetic and pathological features of sporadic AD.

PMID- 20687494
TI  - Huntington's disease.
AB  - Huntington's disease (HD) is one of the most frequently found neurodegenerative
      disorders. Its main clinical manifestations are chorea, cognitive impairment and
      psychiatric disorders. It is an autosomal-dominant disorder with almost complete
      penetrance. The mutation responsible for HD, unstable expansion of a CAG repeat,
      is located in the 5' terminal section of the gene (IT15) that encodes huntingtin
      protein (Htt). The pathophysiology of HD is not entirely clear. One intriguing
      characteristic of HD is the special vulnerability of the striatum tomutated Htt,
      despite similar expression of the mutated protein in other brain regions.
      Aggregation of mutated Htt, transcriptional dysregulation, altered energy
      metabolism, excitotoxicity, impaired axonal transport and altered synaptic
      transmission culminate in neuronal dysfunction and death. There is currently no
      way of preventing or slowing down the disease progression and death usually
      occurs at about 20 years after diagnosis.

PMID- 20687495
TI  - Clinical features and molecular mechanisms of spinal and bulbar muscular atrophy
      (SBMA).
AB  - Spinal and bulbar muscular atrophy (SBMA) is an adult-onset neurodegenerative
      disease characterized by slowly progressive muscle weakness and atrophy. The
      cause of this disease is the expansion of a trinucleotide CAG repeat, which
      encodes the polyglutamine tract, within the first exon of the androgen receptor
      (AR) gene. SBMA exclusively occurs in adult males, whereas both heterozygous and
      homozygous females are usually asymptomatic. Lower motor neurons in the anterior
      horn of the spinal cord and those in the brainstem motor nuclei are predominantly
      affected in SBMA, and other neuronal and nonneuronal tissues are also widely
      involved to some extent. Testosterone-dependent nuclear accumulation of the
      pathogenic AR protein has been considered to be a fundamental step of
      neurodegenerative process, which is followed by several molecular events such as
      transcriptional dysregulation, axonal transport disruption and mitochondrial
      dysfunction. Results of animal studies suggest that androgen deprivation and
      activation of protein quality control systems are potential therapies for SBMA.

PMID- 20687496
TI  - Spinocerebellar ataxia with axonal neuropathy.
AB  - Spinocerebellar ataxia with axonal neuropathy (SCAN 1) is an autosomal recessive
      disorder caused by a specific point mutation (c.1478A>G, p.H493R) in the tyrosyl
      DNA phosphodiesterase (TDP1) gene. Functional and genetic studies suggest that
      this mutation, which disrupts the active site of the Tdp1 enzyme, causes disease
      by a combination of decreased catalytic activity and stabilization of the
      normally transient covalent Tdp1-DNA intermediate. This covalent reaction
      intermediate can form during the repair of stalled topoisomerase I-DNA adducts or
      oxidatively damaged bases at the 3' end of the DNA at a strand break. However,
      our current understanding of the biology of Tdp1 function in humans is limited
      and does not allow us to fully elucidate the disease mechanism.

PMID- 20687497
TI  - Tuberous sclerosis complex and DNA repair.
AB  - Tuberous sclerosis complex (TSC) is an autosomal dominant disorder in humans
      characterized by the development of hamartomas in several organs, including renal
      angiomyolipomas, cardiac rhabdomyomas and subependymal giant cell astrocytomas.
      TSC causes disabling neurologic disorders, including epilepsy, mental retardation
      and autism. Brain lesions, including subependymal and subcortical hamartomas,
      have also been reported in TSC patients. TSC is associated with hamartomas and
      renal cell carcinoma (RCC) as well as sporadic tumors in TSC patient. Renal
      angiomyolipomas associated with TSC tend to be larger, bilateral, multifocal and
      present at a younger age compared with sporadic forms. Tuberous sclerosis complex
      of 2 genes, TSC2 encodes a protein called tuberin that normally exists in an
      active state and forms a heterodimeric complex with hamartin, the protein encoded
      by the TSC1. Deficiency ofTSC2 in Eker rat is associated with the development of
      tumors in several organs including kidney. The majority of renal cell tumors
      observed in the Eker rat originates from renal proximal tubules and are
      histologically similar to renal cell carcinoma in humans. On the other hand,
      mutations in DNA repair enzyme 8-oxoG-DNA glycosylase (OGG1) are associated with
      cancer. OGG1 gene is found somatically mutated in some cancer cells and is highly
      polymorphic among human cancers. Moreover, knockout mice in OGG1 developed
      spontaneously adenoma and carcinoma. We recently show that the constitutive
      expression of OGG1 in heterozygous (TSC2+/-) Eker rat and in angiomyolipomas
      kidney tissue from human is 2-3fold less than in kidney from wild-type rats and
      control human subjects. In addition, we show that loss of TSC2 in kidney tumor of
      Eker rat is associated with loss of OGG1 and accumulation significant levels of
      oxidative DNA damage 8-oxo-deoxyguanine suggesting that TSC2 and OGG1 play a
      major role in renal tumorigenesis.

PMID- 20687498
TI  - Hereditary photodermatoses.
AB  - Photodermatoses are defined as the abnormal reactions of the skin to photons,
      usually those of wavelengths found in sunlight. These reactions can be caused by
      a wide variety of reasons, including defects in repair oflight-induced DNA
      lesions, the interaction of certain chemicals or medications with sunlight to
      produce toxic mediators and photo-induced immune reactions. In this chapter we
      will describe photodermatoses that are associated with hereditary conditions.
      These can be subdivided into several groups: dermatoses caused by abnormal
      metabolic conditions, idiopathic photodermatoses, defects in cancer suppressor
      genes not directly involved in DNA repair but that predispose to photodistributed
      tumors and photosensitivity due to abnormalities in DNA repair pathways. Special
      emphasis will be placed on the relatively recently described UV-sensitive
      syndrome.

PMID- 20687499
TI  - Trichothiodystrophy: Photosensitive, TTD-P, TTD, Tay syndrome.
AB  - Although the term, "trichothiodystrophy" (TTD) refers to the hair anomalies in
      this group of patients, this is a heterogeneous, multisystem disease in which any
      or every organ in the body may be affected. Neuroectodermal derived tissues are
      particularly likely to be involved. This term was introduced by Price et alin
      1980 to designate patients with sulfur-deficient brittle hair, which they
      recognized as a marker for this complex disease and designated it as a
      "neuroectodermal symptom complex". Patients with TTD have brittle hair and nails
      (associated with reduced content ofcysteine-rich matrix proteins), ichthyotic
      skin and physical and mental growth retardation. Ichthyosis is usually apparent
      at birth but much less so after the first few weeks of life. Other frequently
      associated features include ocular cataracts, infections and maternal
      complications related to pregnancy. Atrophy of subcutaneous fat may also be
      present. TTD occurs in a pattern of inheritance consistent with an autosomal
      recessive condition. The disease is extremely heterogeneous in severity and
      extent, with some patients showing no neurological deficiency. Others show
      severe, multisystem disease. Many patients die at a young age, most commonly due
      to infectious disease. TTD is part of a more broadly defined group of diseases
      identified as IBIDS (ichthyosis, brittle hair, impaired intelligence, decreased
      fertility and short stature). Photosensitive cases are also identified as PIBIDS
      (photosensitivity with IBIDS). Cases without manifest ichthyosis are also
      identified as PBIDS. These syndromes defy rigorous definition because of clinical
      variation between patients. The original two cases were described by Tay in
      oriental siblings, whose parents were first cousins; thus the disease is also
      known as Tay syndrome. The hairs in patients with TTD have a distinctive,
      diagnostically useful appearance on polarized light microscopy consisting of
      alternating light and dark bands known as the "tiger tail" anomaly. Diagnosis may
      be confirmed by sulfur content analysis ofhair shafts, which shows decreased
      sulfur and cysteine content. Approximately half of patients with TTD have
      photosensitivity, which correlates with a nudeotide excision repair (NER) defect.
      These patients are designated as having trichothiodystrophy-photosensitive
      (TTDP). Non-photosensitivepatients are designated as having trichothiodystrophy
      nonphotosensitive (TTDN). Skin cancer is very rare in sun-sensitive TTD.

PMID- 20687500
TI  - Cornelia de Lange syndrome.
AB  - Cornelia de Lange syndrome (CdLS) (OMIM # 122470, #300590 and #610759) is an
      autosomal dominant disorder that is classically characterized by typical facial
      features, growth and mental retardation, upper limb defects, hirsutism,
      gastrointestinal and other visceral system involvement. Heterozygous mutations in
      the cohesin regulator, NIPBL, or the cohesin structural components SMC1A and
      SMC3, have been identified in approximately 65% of individuals with CdLS. Cohesin
      regulates sister chromatid cohesion during the mitotis and meiosis. In addition,
      cohesin has been demonstrated to play a critical role in the regulation of gene
      expression. Furthermore, multiple proteins in the cohesin pathway are also
      involved in additional fundamental biological events such as double strand DNA
      break repair, chromatin remodeling and maintaining genomic stability. Here, we
      will discuss the biology ofcohesin and its associated factors, with emphasis on
      the clinical manifestations of CdLS and mechanistic studies of the CdLS related
      proteins.

PMID- 20687501
TI  - Rectal cancer and importance of chemoradiation in the treatment.
AB  - Neoadjuvant chemoradiation is used as a preoperative standard treatment for the
      majority of patients with Stage II/III rectal cancers and, in attempt to
      facilitate surgical intervention, reduce the rate of local recurrence and improve
      overall outcomes in patients suffering from this malignancy. However, this
      modality results in a wide range of clinical responses. In many cases, a
      pathological complete response is achieved, while in others, receiving the same
      form of treatment, the tumor continues to grow. The specific phenotype of the
      tumor plays a major role in rendering tumor cells a survival advantage to the
      cytotoxic effects of chemoradiation. Several factors participating in
      proliferation, cell cycle, apoptosis and hypoxiahave been investigated under a
      variety of conditions in pre-irradiated tissues and post-irradiated tumors.
      Mutations in the genes of these pathways have shown to lead to resistance to
      chemoradiation. This chapter describes colon cancer with emphasis on the
      molecular mechanisms that may lead to chemoradio-resistance of cells with
      cytotoxically induced DNA injury in rectal cancer.

PMID- 20687502
TI  - Familial cutaneous melanoma.
AB  - Approximately 5-10 % of all cutaneous melanomas occur in families with hereditary
      melanoma predisposition. Worldwide, approximately 20-40% of kindreds with
      familial elanoma harbor germline mutations in the CDKN2A gene, located on
      chromosome 9p21, which encodes two different proteins, p16INK4 and p14ARF, both
      involved in regulation of cell cycle progression and induction of senescence. In
      different populations several recurring CDKN2A founder mutations have been
      described. The risk of melanoma in CDKN2A mutations carriers varies between
      populations and is higher in regions with high sun exposure and high incidence of
      melanoma in the general population. Some CDKN2A mutations have been associated
      not only with melanoma but also with increased risk of other malignancies--most
      notably pancreatic carcinoma. A much smaller number of families have germline
      mutations in the CDK4 gene on chromosome 12q14, encoding a cyclin dependent
      kinase which normally interacts with p16INK4A. The management of families with
      hereditary melanoma is discussed.

PMID- 20687503
TI  - Primary immunodeficiency syndromes.
AB  - Several DNA repair pathways have evolved to recognise and repair DNA damaged by
      exogenous and endogenous agents, in order to maintain genomic integrity. Defects
      in these pathways can lead to replication errors, loss or rearrangement ofgenomic
      material, mutation or cancer and eventual death. The creation of many diverse
      lymphocyte receptors to identify potential pathogens has evolved by breaking and
      randomly resorting the gene segments coding for antigen receptors. Subsequent
      steps utilise the ubiquitous repair proteins. Individuals with defective repair
      pathways are increasingly recognised with immunodeficiency, many of whom exhibit
      radiosensitivity. Our understanding of the role of repair proteins in the
      development of adaptive immunity by VDJ recombination, antibody isotype class
      switching and affinity maturation by somatic hyper-mutation has made significant
      progress over the last few years, partly by the identification of new genes
      involved in human disease. We describe the mechanisms involved in the development
      of adaptive immunity relating to DNA repair and describe the clinical
      consequences and treatment developments of primary immunodeficiency resulting
      from such defects.

PMID- 20687504
TI  - Inherited defects of immunoglobulin class switch recombination.
AB  - The investigation of an inherited primary immunodeficiency, the immunoglobulin
      class switch recombination deficiency, has allowed the delineation of complex
      molecular events that underlie antibody maturation in humans. The Activation
      induced cytidine deaminase (AID)-deficiency, characterized by a defect in Class
      Switch Recombination (CSR) and somatic hypermutation, has revealed the master
      role of this molecule in the induction of DNA damage, the first step required for
      these two processes. The description that mutations in the gene encoding the
      Uracil-DNA glycosylase (UNG) lead to defective CSR has been essential for
      defining the DNA-editing activity of AID. Analysis of post meiotic segregation 2
      (PMS2)-deficient patients gave evidence for the role of this mismatch repair
      enzyme in the generation of the DNA breaks that are required for CSR. Novel
      findings are awaited from the study ofyet-genetically undefined CSR-deficiencies,
      probably leading to the identification of AID cofactor(s) and/or proteins
      involved in CSR-induced DNA repair.

PMID- 20687505
TI  - Ligase IV syndrome.
AB  - Ligase IV (LIG4) syndrome belongs to the group of hereditary disorders associated
      with impaired DNA damage response mechanisms. Clinically and morphologically,
      patients affected with this syndrome are characterized by microcephaly, unusual
      facial features, growth retardation, developmental delay, skin anomalies and are
      typically pancytopenic. The disease leads to acute radiosensitivity,
      immunodeficiency and bone marrow abnormalities. LIG4 syndrome arises from
      hypomorphic mutations in the LIG4 gene encoding DNA ligase IV; a component of the
      nonhomologous end-joining machinery, which represents a major mechanism of repair
      of double strand DNA breaks in mammals. The hypomorphic mutations do not
      completely abolish but significantly reduce enzyme function. This results in
      impaired V(D)J recombination, the essential rejoining process in T- and B-cell
      development, in whose ligase IV plays the key role. As a consequence, patients
      with LIG4 syndrome frequently develop multiple immune abnormalities, clinically
      overlapping with severe combined immunodeficiency syndrome.

PMID- 20687506
TI  - Muir-Torre syndrome.
AB  - Muir-Torre syndrome (MTS) is an autosomal dominant genodermatosis that consists
      of unusual cutaneous sebaceous neoplasm, with or without kerathoacantomas and one
      or more low-grade visceral malignancies, with or without colonic polyps, in the
      absence of other predisposing factors. This chapter presents a review of the
      principal clinical and genetic findings in this syndrome and discusses its
      relation with Lynch syndrome.

PMID- 20687507
TI  - Wilms' tumor.
AB  - Wilms' tumor or nephroblastoma is the most frequent renal tumor in children and
      is associated with different congenital anomalies and syndromes. A significant
      number of studies in genetics and molecular biology have improved our
      understanding of this malignancy discovering as well how different genes play a
      critical role in the organogenesis process. Derived from these studies promising
      markers have emerged relating translational medicine with clinical prognosis,
      which has been traditionally defined by the histopathological changes and the
      tumoral stage. During the last 40 years the therapeutic outcomes have improved
      after multi-centric and multidisciplinary efforts represented mainly by The
      National Wilms' Tumor Study Group (currently the Renal Tumor Committee of the
      Children's Oncology Group) from North America and the International Society of
      Paediatric Oncology from Europe and this has served as a role model for
      establishing similar trials for other pediatric tumors. Our aim with this chapter
      of Wilms' tumor is to present the state of knowledge in translational and
      clinical areas in a balanced perspective.

PMID- 20687508
TI  - Cerebro-oculo-facio-skeletal syndrome.
AB  - Cerebro-oculo-facio-skeletal (COFS) syndrome is an autosomal recessive inherited
      disorder characterized by congenital microcephaly, congenital cataracts and/or
      microphthalmia, arthrogryposis, severe developmental delay, severe postnatal
      growth failure and facial dysmorphism with prominent nasal root and/or
      overhanging upper lip. This syndrome is now recognized as a disorder belonging to
      the spectrum of inherited defects in Nucleotide Excision Repair (NER) resulting
      in profound photosensitivity. In COFS syndrome, as in Cockayne syndrome, DNA
      repair is impaired in the transcription-coupled NER pathway, but not in the
      global genome NER pathway. Fourteen cases so far described as COFS syndrome have
      been studied at the molecular levels. All mutations have been found in Cockayne
      syndrome gene, CSB, xeroderma pigmentosum genes, XPD and XPG and ERCC1 gene
      involved in the transcription-coupled NER pathway.

PMID- 20687509
TI  - Dyskeratosis congenita.
AB  - Dyskeratosis congenita (DC) is an inheritable bone marrow failure syndrome
      characterized by reticulated hyperpigmentation, dystrophic nails and oral
      leukoplakia. Another name for the condition is Zinsser-Cole-Engman syndrome.
      Hematologic manifestations usually do not appear in childhood but later in early
      adulthood. Patients are also prone to carcinomas, particularly of the head and
      neck. The disease has X-linked or autosomal dominant/recessive inheritance. Early
      childhood variants (Hoyeraal-Hreidarsson syndrome) are associated with
      immunological abnormalities in the form of low T- and B-cell numbers. Four genes,
      namely DKC1 (codes for dyskerin), TERC and TERT (code for telomerase) and NOP10,
      have been implicated in the pathogenesis; the short telomeres provide a marker
      for genetic linkage studies. Androgens, with or without granulocyte colony
      stimulating factor, have been tried in the treatment of the conditions with
      variable results. Stem cell transplantation from matched sibling donor is
      currently the treatment of choice. It requires modified nonmyeloablative
      conditioning protocols, since the patients with DC are prone to pulmonary and
      hepatic complications.

PMID- 20687510
TI  - Retinoblastoma.
AB  - Retinoblastoma (Rb) is a malignant tumor that originates from developing retina.
      Diagnosis based on clinical signs and symptoms and is usually made in children
      under the age of five years. Mutations in both alleles of the RB1 gene are a
      prerequisite for this tumor to develop. In most patients with sporadic unilateral
      Rb, both RB1 gene mutations occur in somatic cells and are not passed over to
      offspring (nonhereditary Rb). Almost all patients with sporadic bilateral and
      virtually all patients with familial Rb are heterozygous for RB1 gene mutations
      that cause predisposition to Rb (hereditary Rb). In families, Rb predisposition
      is transmitted as an autosomal dominant trait (familial Rb). In addition to Rb,
      patients with hereditary disease also have an increased risk of tumors outside
      the eye (second cancer). This risk is enhanced in patients who have received
      external beam radiotherapy. Analysis of genotype-phenotype associations has shown
      that the mean number of tumor foci that develop in carriers of mutant RB1 alleles
      is variable depending on which functions of the normal allele are retained and to
      what extent. Moreover, phenotypic expression of hereditary retinoblastoma is
      subject to genetic modification. Identification of the genetic factors that
      underlie these effects will not only help to arrive at a more precise prognosis
      but may also point to mechanisms that can be used to reduce the risk of tumor
      development.

PMID- 20687511
TI  - Von Hippel Lindau syndrome.
AB  - Von Hippel-Lindau syndrome (VHLS) is an autosomal dominant familial cancer
      syndrome arising from germ-line inactivation of the VHL gene on the short arm of
      chromosome 3. VHLS manifests in a myriad of hyper-vascular tumors of both benign
      and malignant nature. Incidence of VHLS is roughly 1 in 36,000 live births and
      has over 90% penetrance by the age of 65. Improved understanding of the natural
      history and biology of VHLS has led to the introduction of screening protocols,
      early interventions and improved treatments, all of which resulted in a
      substantially improved prognosis for this disease. Further details
      regardingvariegated molecular pathways and mechanisms ofVHLS are emerging with
      the subsequent advent of novel treatment protocols that are currently in clinical
      trials.

PMID- 20687512
TI  - Interview with Ann Newman, APRN, DSN, CNE candidate for NC House of
      Representatives.

PMID- 20687513
TI  - Health care reform: key provisions related to nursing.

PMID- 20687514
TI  - Why should I get a BSN?

PMID- 20687515
TI  - Tyrosine 112 is essential for organic cation transport by the plasma membrane
      monoamine transporter.
AB  - Plasma membrane monoamine transporter (PMAT) is a polyspecific organic cation
      transporter in the solute carrier 29 (SLC29) family. Previous studies suggested
      that the major substrate recognition sites are located within transmembrane
      domains (TM) 1-6, and interaction of PMAT with organic cations may involve
      aromatic residues. In this study, we analyzed the roles of tyrosine and
      tryptophan residues located within TM1-6 with a goal of identifying potential
      residues involved in substrate recognition and translocation. The six tyrosines
      and one tryptophan in this region were each mutated to alanine followed by
      analysis of the mutant's membrane localization and transport activity toward 1
      methyl-4-phenylpyridinium (MPP(+)), serotonin (5-HT), and dopamine. Two mutants,
      Y85A and Y112A, exhibited normal cell surface expressions but lost their
      transport activities toward organic cations. At position Y85, aromatic
      substitution with phenylalanine or tryptophan fully restored organic cation
      transport activity. Interestingly, at position Y112, phenylalanine substitution
      was not allowed. Tryptophan substitution at Y112 partially restored transport
      activity toward 5-HT and dopamine but severely impaired MPP(+) transport.
      Detailed kinetic analyses revealed that tryptophan substitution at Y85 and Y112
      affected the apparent binding affinity (K(m)) and maximal transport velocity
      (V(max)) in a substrate-dependent manner. Together, our data suggest that Y85 and
      Y112 are important molecular determinants for PMAT function, and Y112 is
      indispensable for optimal interaction with organic cation substrates. Our
      analyses also suggest the involvement of transmembrane domains 1 and 2 in forming
      the substrate permeation pathway of PMAT.

PMID- 20687516
TI  - Enhanced DNA accessibility and increased DNA damage induced by the absence of
      poly(ADP-ribose) hydrolysis.
AB  - Poly(ADP-ribose) (PAR) is a therapeutic target primarily identified through
      inhibiting its synthesis by PAR polymerase-1 (PARP-1). However, inhibiting its
      hydrolysis by PAR glycohydrolase (PARG) has therapeutic potential in cancer.
      Unknown is the effect of elevated PAR levels on cellular processes and if this
      effect can enhance the therapeutic value of PARG. Here, we demonstrate in PARG
      null embryonic trophoblast stem (TS) cells that the absence of PAR hydrolysis led
      to PAR-modified histones H1, H2A, and H2B. To determine if this led to the
      differential vulnerability of DNA to modification, TS cells were treated with DNA
      modifying agents. The results demonstrate increased DNA laddering by micrococcal
      nuclease and an increased amount of DNA intercalation by acridine orange in PARG
      null-TS cells. This increased access to PARG null-TS cell DNA was further
      verified by the detection of increased DNA damage following treatment with UV
      radiation and a minimal dose of the DNA-alkylating agent N-methyl-N'-nitro-N
      nitrosoguanidine. Further, this DNA damage was predominantly unrepaired 12 h
      after treatment in PARG null-TS cells. Finally, TS cells were treated with DNA
      modifying chemotherapeutic agents. The results demonstrate up to 4-fold increases
      in cell death in PARG null-TS cells after treatment with epirubicin or sub-IC(50)
      doses of cisplatin and cyclophosphamide. Taken together, we provide compelling
      evidence that increased DNA access induced by the absence of PARG enhances the
      efficacy of DNA-modifying agents. Thus, this study demonstrates that greater DNA
      accessibility, increased DNA damage, and increased cell death all contribute to
      the PARG null cell phenotype in response to genotoxic stress.

PMID- 20687518
TI  - Nature and strength of M-S bonds (m = Au, Ag, and Cu) in binary alloy gold
      clusters.
AB  - The interactions of pure (Au(k), Ag(k), and Cu(k); k = 1-3) and binary alloy
      (Au(n)Ag(m) and Au(n)Cu(m); m + n = k <or= 3) metal clusters with hydrogen
      sulfide (H(2)S) have been investigated by using density functional theory (BP86,
      B3LYP, and CAM-B3LYP) and ab initio methods (MP2 and CCSD(T)), with a focus on
      the nature of metal-sulfur bonds. Binding energy calculations indicate that for
      pure metal clusters, the tendency of metal to interact with H(2)S has the order
      of Au > Cu > Ag. In binary alloy clusters, alloying Au(k) with copper and silver
      decreases the attraction of Au toward H(2)S, while alloying Ag(k) and Cu(k) by
      gold increases the attraction of Ag and Cu toward H(2)S, significantly.
      Dissociation energy values for isolated metal clusters specify the more favorable
      formation of binary alloy clusters (Au(n)Ag(m) and Au(n)Cu(m)) over pure ones.
      The nature of M-S bonds (M = Au, Ag, and Cu) is also interpreted by means of the
      quantum theory of atoms in molecules (QTAIM), natural bond orbital (NBO), and
      energy decomposition analysis (EDA). According to these theories, the M-S bonds
      are found to be partially electrostatic and partially covalent. EDA results
      identify that these bonds have less than 35% covalent character and more than 65%
      electrostatic, and the covalent character increases in different metals in the
      order Au > Cu > Ag.

PMID- 20687517
TI  - Nonadditive empirical force fields for short-chain linear alcohols: methanol to
      butanol. Hydration free energetics and Kirkwood-Buff analysis using charge
      equilibration models.
AB  - Building upon the nonadditive electrostatic force field for alcohols based on the
      CHARMM charge equilibration (CHEQ) formalism, we introduce atom-pair specific
      solute-solvent Lennard-Jones (LJ) parameters for alcohol-water interaction force
      fields targeting improved agreement with experimental hydration free energies of
      a series of small molecule linear alcohols as well as ab initio water-alcohol
      geometries and energetics. We consider short-chain, linear alcohols from methanol
      to butanol as they are canonical small-molecule organic model compounds to
      represent the hydroxyl chemical functionality for parametrizing biomolecular
      force fields for proteins. We discuss molecular dynamics simulations of dilute
      aqueous solutions of methanol and ethanol in TIP4P-FQ water, with particular
      discussion of solution densities, structure defined in radial distribution
      functions, electrostatic properties (dipole moment distributions), hydrogen
      bonding patterns of water, as well as a Kirkwood-Buff (KB) integral analysis.
      Calculation of the latter provides an assessment of how well classical force
      fields parametrized to at least semiquantitatively match experimental hydration
      free energies capture the microscopic structures of dilute alcohol solutions; the
      latter translate into macroscopic thermodynamic properties through the
      application of KB analysis. We find that the CHEQ alcohol force fields of this
      work semiquantitatively match experimental KB integrals for methanol and ethanol
      mole fractions of 0.1 and 0.2. The force field combination qualitatively captures
      the concentration dependence of the alcohol-alcohol and water-water KB integrals,
      but due to inadequacies in the representation of the microscopic structures in
      such systems (which cannot be parametrized in any systematic fashion), a priori
      quantitative description of alcohol-water KB integrals remains elusive.

PMID- 20687519
TI  - Electric field controlled magnetic anisotropy in a single molecule.
AB  - We have measured quantum transport through an individual Fe(4) single-molecule
      magnet embedded in a three-terminal device geometry. The characteristic zero
      field splittings of adjacent charge states and their magnetic field evolution are
      observed in inelastic tunneling spectroscopy. We demonstrate that the molecule
      retains its magnetic properties and, moreover, that the magnetic anisotropy is
      significantly enhanced by reversible electron addition/subtraction controlled
      with the gate voltage. Single-molecule magnetism can thus be electrically
      controlled.

PMID- 20687520
TI  - Identifying the specific nanostructures responsible for the high thermoelectric
      performance of (Bi,Sb)2Te3 nanocomposites.
AB  - Herein, we report the synthesis of multiscale nanostructured p-type
      (Bi,Sb)(2)Te(3) bulk materials by melt-spinning single elements of Bi, Sb, and Te
      followed by a spark plasma sintering process. The samples that were most
      optimized with the resulting composition (Bi(0.48)Sb(1.52)Te(3)) and specific
      nanostructures showed an increase of approximately 50% or more in the figure of
      merit, ZT, over that of the commercial bulk material between 280 and 475 K,
      making it suitable for commercial applications related to both power generation
      and refrigeration. The results of high-resolution electron microscopy and small
      angle and inelastic neutron scattering along with corresponding thermoelectric
      property measurements corroborate that the 10-20 nm nanocrystalline domains with
      coherent boundaries are the key constituent that accounts for the resulting
      exceptionally low lattice thermal conductivity and significant improvement of ZT.

PMID- 20687521
TI  - Nanomembrane-based mesoscopic superconducting hybrid junctions.
AB  - A new method for combining top-down and bottom-up approaches to create
      superconductor-normal metal-superconductor niobium-based Josephson junctions is
      presented. Using a rolled-up semiconductor nanomembrane as scaffolding, we are
      able to create mesoscopic gold filament proximity junctions. These are created by
      electromigration of gold filaments after inducing an electric field mediated
      breakdown in the semiconductor nanomembrane, which can generate nanometer sized
      structures merely using conventional optical lithography techniques. We find that
      the created point contact junctions exhibit large critical currents of a few
      milliamps at 4.2 K and an I(c)R(n) product placing their characteristic frequency
      in the terahertz region. These nanometer-sized filament devices can be further
      optimized and integrated on a chip for their use in superconductor hybrid
      electronics circuits.

PMID- 20687522
TI  - Sub-10-nm nanochannels by self-sealing and self-limiting atomic layer deposition.
AB  - We report on a novel fabrication method of a nanochannel ionic field effect
      transistor (IFET) structure with sub-10-nm dimensions. A self-sealing and self
      limiting atomic layer deposition (ALD) facilitates the fabrication of lateral
      type nanochannels smaller than the e-beam or optical lithographic limits. Using
      highly conformal ALD film structures, including TiO(2), TiO(2)/TiN, and
      Al(2)O(3)/Ru, we have fabricated lateral sub-10-nm nanochannels with good control
      over channel diameter. Nanochannels surrounded by core/shell (high-k
      dielectric/metal) layers give rise to all-around-gating IFETs, an important
      functional element in an electrofluidic-based circuit system.

PMID- 20687523
TI  - Off-pathway status for the alkali molten globule of horse ferricytochrome C.
AB  - The Na(+)-stabilized alkali molten globule (B-state) of horse ferricytochrome c
      produced at pH 12.9 in 2 M NaCl has been studied to find out its relevance to the
      kinetic folding pathway of the protein. Details of stopped-flow kinetics indicate
      that the B-state when driven to fold at pH 11.5 goes through a submillisecond
      burst expansion to a state B' which must unfold to the base-denatured U(B)-state
      before folding to the alkaline native state, N(B). This folding hallmark suggests
      that the B-state is a dead-end or off-pathway species, playing apparently an
      unclear role in the folding kinetics. Interestingly, the folding kinetics of the
      B-state at a final pH of 7 is very similar to that observed for the guanidinium
      unfolded ferricytochrome c (U) at pH 7. Both B and U exhibit a submillisecond
      burst phase followed by three observable phases, fast, medium, and slow, with
      matching rate constants for the fast phase, suggesting that B- and U-states share
      a common folding mechanism. Even the minima in the folding chevrons for the B-
      and U-states appear at the same denaturant concentration, but the former is
      shifted vertically upward and has shallower limbs, suggesting that the transition
      state relevant for the B-state folding is relatively more compact with greater
      surface burial allaying large-scale diffusive migration of chain segments. It is
      concluded that the B-state is not a good model for the kinetic molten globule of
      cytochrome c. Part of the reason for such atypical response of a typical molten
      globule may possibly be related to misligation of the ferric heme with lysyl side
      chains at the extreme alkaline pH required to produce the B-state. To eliminate
      this possibility, the companion paper [Bhuyan, A. K. (2010) Biochemistry (DOI
      10.1021/bi100881n )] studies the B-state of ferrocytochrome c where ligation of
      the heme with any intrapolypeptide side chain is completely suppressed. The study
      concludes that the B-state is kinetically an abortive species.

PMID- 20687524
TI  - The off-pathway status of the alkali molten globule is unrelated to heme
      misligation and trans-pH effects: experiments with ferrocytochrome c.
AB  - The relevance of the alkali molten globule (B-state) to the folding pathway of
      cytochrome c has been studied further with the reduced state of the protein for
      which the B-state is prepared by ligating the ferrous heme iron with extrinsic CO
      under 1 mM gas concentration in the presence of NaCl. The CO derivative of
      ferrocytochrome c is desirable not only because it abrogates the interference of
      non-native heme ligands but the GdnHCl-unfolded protein refolds fast without
      deviating from the intrinsic folding pathway of the protein. Interstate folding
      unfolding kinetics at alkaline and neutral pH conditions reveal that the B-state
      chain initially expands in the submillisecond regime in order to fold correctly
      to the native state. In this sense, it is an off-pathway nonproductive species
      which must dissipate some non-native elements before proceeding to fold. It is
      concluded that the alkali molten globule does not correspond to any possible
      transient structure in the folding pathway of cytochrome c.

PMID- 20687525
TI  - Effect of the protonation state of the titratable residues on the inhibitor
      affinity to BACE-1.
AB  - BACE-1 is one of the aspartic proteases involved in the cleavage of beta amyloid
      peptide, an initial step in the formation of amyloid plaques whose toxicity
      induces neuron death in Alzheimer's disease patients. One of the central issues
      in the search of novel BACE-1 inhibitors is the optimum pH for the binding of
      inhibitors to the enzyme. It is known that the enzyme has optimal catalytic
      activity at acidic pH, while cell active inhibitors may bind optimally at higher
      pH. In this work we determine the effect of the pH on the affinities of a set of
      inhibitors, with a variety of chemical motifs, for the ectodomain region of BACE
      1 by a surface plasmon resonance (SPR) biosensor based assay. In order to
      understand the molecular interactions that underlie the diverse optimum pH for
      the binding of the various inhibitors as observed experimentally, we have
      calculated the titration curves for a set of BACE-1 ligand complexes. The results
      indicate that the pK(a) values of the titratable residues of the protein depend
      on the nature of the ligand involved, in disagreement with previous work. The
      enzyme-inhibitor structures with the resulting protonation states at pH values
      4.5 and 7.4 served as the starting point for the prediction of the pH-dependent
      binding ranking. Our calculations reproduced the entire affinity ranking observed
      upon pH increase and most of the binding trends among inhibitors, especially at
      low pH. Finally, our cell-based assays indicate a possible correlation between
      high inhibitor affinity at both acidic and neutral pH values, with optimal cell
      response, a result that may open new venues for the search of potent BACE-1
      inhibitors that are active at the cellular level.

PMID- 20687526
TI  - Thermodynamics of peptide-RNA recognition: the binding of a Tat peptide to TAR
      RNA.
AB  - RNA-peptide interactions have been intensively studied at the structural level;
      however, in the absence of thermodynamic studies, the molecular forces that
      dictate the binding specificities and affinities remain elusive. Here we evaluate
      the thermodynamics (DeltaG, DeltaH, DeltaS) of HIV-1 TAR RNA hairpin and Tat
      peptide interaction as well as the hydration changes that accompany these
      interactions, through a series of calorimetric, spectroscopic, and osmotic stress
      studies. Tat peptide binding enhances the thermal stability of the TAR RNA
      hairpin; however, the thermal enhancement decreases with increasing Na(+)
      concentration. The equilibrium association constant (K(a)) is determined by
      fluorescence titrations and examined as a function of Na(+) concentration and
      temperature. The binding constant (K(a)) decreases with increasing Na(+)
      concentration. The binding free energy (DeltaG) is found to have a large
      nonpolyelectrolyte component with release of a single counterion upon binding.
      The ITC profiles showed two independent sites binding, indicating specific as
      well as nonspecific interactions. The enthalpy changes associated with both the
      binding sites are found to be more negative for the binding process at lower salt
      concentration of 20 mM Na(+). Our binding studies under osmotic stress conditions
      show that there is a release of 28 (+/-4) and 21 (+/-3) water molecules upon
      complex formation at 20 and 80 mM Na(+) concentration supporting the observed
      positive entropy contributions and accounting for discrepancies between
      DeltaH(cal) and DeltaH(vH). In aggregate, our results suggest that the hydrogen
      bonding of arginine to TAR RNA dictates the binding interaction.

PMID- 20687527
TI  - Driving forces for adsorption of amphiphilic peptides to the air-water interface.
AB  - We have studied the partitioning of amphiphilic peptides at the air-water
      interface. The free energy of adsorption from bulk to interface was calculated by
      determining the potential of mean force via atomistic molecular dynamics
      simulations. To this end a method is introduced to restrain or constrain the
      center of mass of a group of molecules in a periodic system. The model
      amphiphilic peptides are composed of alternating valine and asparagine residues.
      The decomposition of the free energy difference between the bulk and interface is
      studied for different peptide block lengths. Our analysis revealed that for short
      amphiphilic peptides the surface driving force dominantly stems from the
      dehydration of hydrophobic side chains. The only opposing force is associated
      with the loss of orientational freedom of the peptide at the interface. For the
      peptides studied, the free energy difference scales linearly with the size of the
      molecule, since the peptides mainly adopt extended conformations both in bulk and
      at the interface. The free energy difference depends strongly on the water model,
      which can be rationalized through the hydration thermodynamics of hydrophobic
      solutes. Finally, we measured the reduction of the surface tension associated
      with complete coverage of the interface with peptides.

PMID- 20687528
TI  - Coarse-grained time-dependent density functional simulation of charge transfer in
      complex systems: application to hole transfer in DNA.
AB  - We present a coarse-grained tight-binding method based on density functional
      theory (DFT) for the simulation of charge transfer in complex materials. The
      charge-transfer parameters are computed using a fragment-orbital approach
      combined with the approximative DFT method self-consistent charge density
      functional tight binding (SCC-DFTB), which allows to follow the dynamics of
      excess charge along nanosecond MD trajectories, still accounting for the
      important impact of structural fluctuations and solvent effects. Since DFT
      suffers from the self-interaction error, which would lead to a delocalization of
      the hole charge over the entire system, we study the effect of an empirical self
      interaction correction in detail. The wave function of the excess charge is
      propagated within the framework of time-dependent DFT, where the electron (hole)
      and the atomic system are propagated simultaneously according to the derived
      coupled equations of motion. In the case of DNA, the solvent polarization effects
      are a dominant factor affecting the hole transport. The hole charge polarizes the
      surrounding water, which in turn supports a localization of the hole charge--a
      water polaron is formed, extended dynamically over several nucleobases. As this
      polarization of water accompanies the migrating hole, the motion of hole is
      significantly slowed down due to the solvent reorganization energy involved. The
      estimated hopping rate between neighboring adenines in poly(A)-DNA is in the
      order of 100 ns(-1), and our simulations clearly show that the charge transfer
      occurs in a nonadiabatic fashion, due to the small average electronic coupling of
      around 0.06 eV.

PMID- 20687529
TI  - Noncovalent interaction of alpha(2)-antiplasmin with fibrin(ogen): localization
      of alpha(2)-antiplasmin-binding sites.
AB  - Covalent incorporation (cross-linking) of plasmin inhibitor alpha(2)-antiplasmin
      (alpha(2)-AP) into fibrin clots increases their resistance to fibrinolysis. We
      hypothesized that alpha(2)-AP may also interact noncovalently with fibrin prior
      to its covalent cross-linking. To test this hypothesis, we studied binding of
      alpha(2)-AP to fibrin(ogen) and its fragments by an enzyme-linked immunosorbent
      assay (ELISA) and surface plasmon resonance. The experiments revealed that
      alpha(2)-AP binds to polymeric fibrin and surface-adsorbed fibrin(ogen), while no
      binding was observed with fibrinogen in solution. To localize the alpha(2)-AP
      binding sites, we studied the interaction of alpha(2)-AP with the fibrin(ogen)
      derived D(1), D-D, and E(3) fragments, and the recombinant alphaC region and its
      constituents, alphaC connector and alphaC domain and its subdomains, which
      together encompass practically the whole fibrin(ogen) molecule. In the ELISA,
      alpha(2)-AP bound to immobilized D(1), D-D, alphaC region, alphaC domain, and its
      C-terminal subdomain. The binding was Lys-independent and was not inhibited by
      plasminogen or tPA. Furthermore, the affinity of alpha(2)-AP for D-D was
      significantly increased in the presence of plasminogen, while that to the alphaC
      domain remained unaffected. Altogether, these results indicate that the
      fibrin(ogen) D region and the C-terminal subdomain of the alphaC domain contain
      high-affinity alpha(2)-AP-binding sites that are cryptic in fibrinogen and
      exposed in fibrin or adsorbed fibrinogen, and the presence of plasminogen
      facilitates interaction of alpha(2)-AP with the D regions. The discovered
      noncovalent interaction of alpha(2)-AP with fibrin may contribute to regulation
      of the initial stage of fibrinolysis and provide proper orientation of the cross
      linking sites to facilitate covalent cross-linking of alpha(2)-AP to the fibrin
      clot.

PMID- 20687530
TI  - Ligand influence on metal aggregation: a unique bonding mode for
      pyridylpyrrolides.
AB  - The synthesis and characterization of a Cu(I) complex with a cis-bidentate
      monoanionic nitrogenous ligand, 2-pyridylpyrrolide, L, is reported. This shows
      binding of one base B = MeCN or CO per copper in a species LCu(B), but this
      readily releases the volatile ligand under vacuum with aggregation of transient
      LCu to a mixture of two enantiomers of a chiral trimer: a zwitterion containing
      inequivalent Cu(I) centers, possible via a new bonding mode of pyridylpyrrolide,
      and one with nitrogen lone pairs donating to two different metals. Density
      functional theory calculations show the energetics of both ligand binding and
      aggregation (including dimer and monomer alternatives), as well as the ability of
      this ligand to rotate away from planarity to accommodate a bridging structural
      role. The trimer serves as a synthon for the simple fragment LCu.

PMID- 20687531
TI  - New members of the {Fe(NO)2}10 dinitrosyliron complexes bound with [thiolate,
      thiolate] and [amide, amide] ligations.
AB  - The first dianionic {Fe(NO)(2)}(10) dinitrosyliron complexes (DNICs)
      [Fe(SC(7)H(4)SN)(2)(NO)(2)](2-) (1) and [Fe(OC(7)H(4)SN)(2)(NO)(2)](2-) (2),
      coordinated with thiolates and amides, were prepared by the reaction of
      Fe(TMEDA)(NO)(2) with 2 equiv of ligands [SC(7)H(4)SN](-) and [OC(7)H(4)SN](-),
      respectively. The reversible interconversion between the dianionic
      {Fe(NO)(2)}(10) DNICs 1/2 and the anionic
      {Fe(NO)(2)}(9)[Fe(SC(7)H(4)SN)(2)(NO)(2)](-) (3)/[Fe(OC(7)H(4)SN)(2)(NO)(2)](-)
      (4), respectively, was demonstrated. The transformation of DNICs 2 and 3 into the
      thermally stable DNICs 1 and 4, respectively, via the ligand-exchange reaction
      reveals that [OC(7)H(4)SN](-) shows a high binding affinity toward the
      {Fe(NO)(2)}(9) motif and [SC(7)H(4)SN](-) prefers the {Fe(NO)(2)}(10) motif. This
      result rationalizes that the intermolecular electron transfer from DNIC 2 to DNIC
      3 occurs to lead to the formation of the more thermally stable DNICs 1 and 4 upon
      the reaction of DNICs 2 and 3 in tetrahydrofuran.

PMID- 20687532
TI  - Differences of pH-dependent mechanisms on generation of hydride donors using
      Ru(II) complexes containing geometric isomers of NAD+ model ligands: NMR and
      radiolysis studies in aqueous solution.
AB  - The pH-dependent mechanism of the reduction of the nicotinamide adenine
      dinucleotide (NADH) model complex [Ru(bpy)(2)(5)](2+) (5 = 3-(pyrid-2'-yl)-4
      azaacridine) was compared to the mechanism of the previously studied geometric
      isomer [Ru(bpy)(2)(pbn)](2+) (pbn = 2-(pyrid-2'-yl)-1-azaacridine, previously
      referred to as 2-(pyrid-2'-yl)-benzo[b]-1,5-naphthyridine) in aqueous media. The
      exposure of [Ru(bpy)(2)(5)](2+) to CO(2)(*-) leads to the formation of the one
      electron reduced species (k = 4.4 x 10(9) M(-1) s(-1)). At pH < 11.2, the one
      electron reduced species can be protonated, k = 2.6 x 10(4) s(-1) in D(2)O.
      Formation of a C-C bonded dimer is observed across the pH range of 5-13 (k = 4.5
      x 10(8) M(-1) s(-1)). At pH < 11, two protonated radical species react to form a
      stable C-C bonded dimer. At pH > 11, dimerization of two one-electron reduced
      species is followed by disproportionation to one equivalent starting complex
      [Ru(bpy)(2)(5)](2+) and one equivalent [Ru(bpy)(2)(5HH)](2+). The structural
      difference between [Ru(bpy)(2)(pbn)](2+) and [Ru(bpy)(2)(5)](2+) dictates the
      mechanism and product formation in aqueous medium. The exchange of the nitrogen
      and carbon atoms on the azaacridine ligands alters the accessibility of the
      dimerization reactive site, thereby changing the mechanism and the product
      formation for the reduction of the [Ru(bpy)(2)(5)](2+) compound.

PMID- 20687533
TI  - Conformation and intermolecular interactions of SA2 peptides self-assembled into
      vesicles.
AB  - Previously we have shown that the recombinantly produced SA2 amphiphilic
      oligopeptide (Ac-Ala-Ala-Val-Val-Leu-Leu-Leu-Trp-Glu-Glu-COOH) self-assembles
      into nanovesicles (van Hell et al. 2007). In this study, the intermolecular
      interactions that contribute to the formation of such peptide vesicles are
      examined. First, analysis of a 3-hydroxyflavone fluorescent probe inserted into
      the peptide assemblies demonstrated that the peptide self-assembly is based on
      hydrophobic clustering. The polarity of this hydrophobic microenvironment was
      comparable to that of negatively charged lipid bilayers. A substantial level of
      hydration at the hydrophilic-hydrophobic interface was detected, as was further
      confirmed by tryptophan fluorescence analysis. However, organic solvents such as
      acetonitrile, tetrahydrofuran, or ethanol could not disrupt SA2 oligopeptide
      vesicles, whereas these solvents fully disintegrated lipid vesicles. Instead, the
      SA2 assembly immediately disintegrated in hydrogen breaking solvents such
      dimethylsulfoxide and dimethylformamide, suggesting the involvement of additional
      intermolecular interactions via hydrogen bonding. Circular dichroism and Fourier
      transform infrared spectroscopy excluded well-defined patterns of intramolecular
      hydrogen bonding and indicated the polyproline type II as the dominant SA2
      peptide conformation, which enables intermolecular hydrogen bonding. All-atom
      computational simulations were used to confirm the presence of such
      intermolecular hydrogen bonds and degrees of hydration. On the basis of the
      experimental and computational data presented, we propose a model of an
      interdigitated peptide assembly that involves intermolecular hydrogen bonding in
      addition to hydrophobic interactions that stabilize SA2 oligopeptide vesicles.

PMID- 20687534
TI  - The hoiamides, structurally intriguing neurotoxic lipopeptides from Papua New
      Guinea marine cyanobacteria.
AB  - Two related peptide metabolites, one a cyclic depsipeptide, hoiamide B (2), and
      the other a linear lipopeptide, hoiamide C (3), were isolated from two different
      collections of marine cyanobacteria obtained in Papua New Guinea. Their
      structures were elucidated by combining various techniques in spectroscopy,
      chromatography, and synthetic chemistry. Both metabolites belong to the unique
      hoiamide structural class, characterized by possessing an acetate extended and S
      adenosyl methionine modified isoleucine unit, a central triheterocyclic system
      comprised of two alpha-methylated thiazolines and one thiazole, and a highly
      oxygenated and methylated C-15 polyketide unit. In neocortical neurons, the
      cyclic depsipeptide 2 stimulated sodium influx and suppressed spontaneous Ca(2+)
      oscillations with EC(50) values of 3.9 microM and 79.8 nM, respectively, while 3
      had no significant effects in these assays.

PMID- 20687535
TI  - Synthesis and properties of oligonucleotides carrying isoquinoline imidazo[1,2
      a]azine fluorescent units.
AB  - Oligonucleotides carrying novel fluorescent compounds with a dipolar isoquinoline
      imidazo[1,2-a]azine core were prepared. Analysis of the melting curves
      demonstrates that DNA duplexes carrying these fluorescent labels at their ends
      have a slight increase in DNA duplex stability. The UV absorption and fluorescent
      properties of the oligonucleotide conjugates were analyzed. The fluorescent label
      is sensitive to duplex formation, as cooperative melting curves are also observed
      at 366 nm and fluorescence has a large increase upon denaturation. Cell uptake
      studies allow observation of these fluorescently labeled oligonucleotides
      internalized into HeLa cells.

PMID- 20687536
TI  - Quantitative analysis of localized surface plasmons based on molecular probing.
AB  - We report on the quantitative characterization of the plasmonic optical near
      field of a single silver nanoparticle. Our approach relies on nanoscale molecular
      molding of the confined electromagnetic field by photoactivated molecules. We
      were able to directly image the dipolar profile of the near-field distribution
      with a resolution better than 10 nm and to quantify the near-field depth and its
      enhancement factor. A single nanoparticle spectral signature was also assessed.
      This quantitative characterization constitutes a prerequisite for developing
      nanophotonic applications.

PMID- 20687537
TI  - A gigaseal obtained with a self-assembled long-lifetime lipid bilayer on a single
      polyelectrolyte multilayer-filled nanopore.
AB  - A lipid bilayer with gigaohm resistance was fabricated over a single 800 nm pore
      in a Si3N4 chip using 50 nm liposomes. The nanopore was prefilled with a
      polyelectrolyte multilayer (PEM) that triggered the spontaneous fusion of the
      lipid vesicles. Pore-forming peptide melittin was incorporated in the bilayer,
      and single channel activities were monitored for a period of 2.5 weeks. The long
      lifetime of the system enabled the observation of the time-dependent
      stabilization effect of the melittin open state upon bias application.

PMID- 20687538
TI  - Polycationic nanodrug covered with hyaluronic acid for treatment of P
      glycoprotein overexpressing cancer cells.
AB  - To treat cancer cells overexpressing P-glycoprotein (P-gp), we propose a new
      concept using a nanodrug. The nanodrug was prepared from polyethyleneimine
      (PEI)/all-trans retinoic acid (ATRA) conjugates (PRA) and covered with hyaluronic
      acid (HA) to control the cytotoxicity of PRA (yielding PRA-H). The size
      distribution of PRA-H was narrow, with an average particle size of approximately
      143 nm. Its superior stability in phosphate-buffered saline (PBS) was verified by
      monitoring changes in particle size and zeta potential for 24 h, which were
      negligible. In contrast, PEI-H (not conjugated with ATRA) exhibited a significant
      change in particle size and zeta potential. Although PRA was highly cytotoxic
      against HCT-8 and SNU-484 cancer cells, both of which overexpress P-gp, the
      cytotoxicity was significantly reduced by shielding with HA. The cytotoxicity of
      PRA-H was recovered by treatment with hyaluronidase (HAase), which degrades HA
      and is present in tumors at high concentrations. These results were confirmed by
      optical microscopy, fluorescence-activated cell sorting (FACs) analysis, and
      confocal microscopy. The cytotoxic mechanism of PRA was revealed as a type of
      necrotic lysis by FACs analysis with propidium iodide (PI) staining. Furthermore,
      PRA increased HCT-8 cell (colon cancer) permeability to doxorubicin (DOX).
      Therefore, we concluded that PRA-H is a promising new candidate for the treatment
      of cells with multidrug resistance (MDR) induced by overexpression of P-gp and
      cancer stem cells.

PMID- 20687539
TI  - Atmospheric oxidation of trichloroethylene: an ab initio study.
AB  - The atmospheric oxidation of trichloroethylene has previously been studied
      experimentally. Phosgene is thought to be the dominant product, although the
      mechanism of production is not well understood. Additionally, studies omitting a
      chlorine scavenger show the production of dichloroacetyl chloride. This influence
      of the chlorine atom on the trichloroethylene oxidation is not well understood.
      Using ab initio methods, this study presents a comprehensive computational study
      of both the hydroxyl radical and chlorine atom initiated atmospheric oxidation
      mechanisms of trichloroethylene (C(2)HCl(3)). Potential energy surfaces,
      including activation energies and enthalpies, are determined. The results from
      this study, in connection with experimental work, confirm the influence of the Cl
      initiated oxidation in determining the product profile of the trichloroethylene
      oxidation. These products include dichloroacetyl chloride [Cl(2)CHC(O)Cl], formyl
      chloride [CH(O)Cl], phosgene [C(O)Cl(2)], and regeneration of the chlorine atom.

PMID- 20687540
TI  - Cobalt-porphyrin catalyzed electrochemical reduction of carbon dioxide in water.
      1. A density functional study of intermediates.
AB  - The reduction of carbon dioxide by cobalt porphyrins is thought to be a multistep
      reaction with several possible intermediates and reaction pathways. We here
      investigate a number of possible intermediates in this reaction using density
      functional theory, including both hybrid (B3LYP) and pure (PBE and BP86)
      functionals. Optimum structures are located, and harmonic vibrational frequencies
      and thermal corrections are computed for the low-lying electronic states for all
      intermediates. Free energies of solvation are predicted for all species,
      providing a reaction profile in the aqueous phase, which enables identification
      of likely pathways. Finally, the reaction energy for the binding of carbon
      dioxide to the cobalt porphine cation is determined in the gas phase and in
      solution.

PMID- 20687541
TI  - Primary and embedded steel imports to the U.S.: implications for the design of
      border tax adjustments.
AB  - Carbon Border Tax Adjustments (BTAs) are a politically popular strategy for
      avoiding competitive disadvantage problems when a country implements a unilateral
      climate change policy. A BTA taxes carbon embodied in imported goods in order to
      protect domestic industry and motivate other countries to implement climate
      change policy. To estimate the effectiveness of a BTA, is it is necessary to know
      which products are covered, where they were originally produced and ultimately
      exported from, and how the covered amount compares to total production in foreign
      countries. Using a scrap-adjusted, mixed-unit input-output model in conjunction
      with a multiregional input-output model, this analysis evaluates the
      effectiveness of BTAs for the case study of U.S. steel imports. Most imported
      steel by mass is embedded in finished products (60%), and 30% of that steel is
      produced in a different country than the one from which the final good is
      exported. Given the magnitudes involved and complexities of global supply chains,
      a BTA that protects domestic industry will be a challenge to implement. We
      propose a logistically feasible BTA structure that minimizes the information
      burden while still accounting for these complexities. However, the amount of
      steel imported to the U.S. is negligible (5%) compared to foreign production in
      BTA-eligible countries and is unlikely to motivate affected countries to impose
      an emissions reduction policy.

PMID- 20687542
TI  - Coastal loading and transport of Escherichia coli at an embayed beach in Lake
      Michigan.
AB  - A Chicago beach in southwest Lake Michigan was revisited to determine the
      influence of nearshore hydrodynamic effects on the variability of Escherichia
      coli (E. coli) concentration in both knee-deep and offshore waters. Explanatory
      variables that could be used for identifying potential bacteria loading
      mechanisms, such as bed shear stress due to a combined wave-current boundary
      layer and wave runup on the beach surface, were derived from an existing wave and
      current database. The derived hydrodynamic variables, along with the actual
      observed E. coli concentrations in the submerged and foreshore sands, were
      expected to reveal bacteria loading through nearshore sediment resuspension and
      swash on the beach surface, respectively. Based on the observation that onshore
      waves tend to result in a more active hydrodynamic system at this embayed beach,
      multiple linear regression analysis of onshore-wave cases further indicated the
      significance of sediment resuspension and the interaction of swash with gull
      droppings in explaining the variability of E. coli concentration in the knee-deep
      water. For cases with longshore currents, numerical simulations using the
      Princeton Ocean Model revealed current circulation patterns inside the embayment,
      which can effectively entrain bacteria from the swash zone into the central area
      of the embayed beach water and eventually release them out of the embayment. The
      embayed circulation patterns are consistent with the statistical results that
      identified that 1) the submerged sediment was an additional net source of E. coli
      to the offshore water and 2) variability of E. coli concentration in the knee
      deep water contributed adversely to that in the offshore water for longshore
      current cases. The embayed beach setting and the statistical and numerical
      methods used in the present study have wide applicability for analyzing
      recreational water quality at similar marine and freshwater sites.

PMID- 20687543
TI  - Photoreactivity of carboxylated single-walled carbon nanotubes in sunlight:
      reactive oxygen species production in water.
AB  - Very limited information exists on transformation processes of carbon nanotubes
      in the natural aquatic environment. Because the conjugated pi-bond structure of
      these materials is efficient in absorbing sunlight, photochemical transformations
      are a potential fate process with reactivity predicted to vary with their
      diameter, chirality, number and type of defects, functionalization, residual
      metal catalyst and amorphous carbon content, and with the composition of the
      water, including the type and composition of materials that act to disperse them
      into the aqueous environment. In this study, the photochemical reactions
      involving colloidal dispersions of carboxylated single-walled carbon nanotubes
      (SWNT-COOH) in sunlight were examined. Production of reactive oxygen species
      (ROS) during irradiation occurs and is evidence for potential further
      phototransformation and may be significant in assessing their overall
      environmental impacts. In aerated samples exposed to sunlight or to lamps that
      emit light only within the solar spectrum, the probe compounds, furfuryl alcohol
      (FFA), tetrazolium salts (NBT2+ and XTT), and p-chlorobenzoic acid (pCBA), were
      used to indicate production of 1O2, O2.-, and .OH, respectively. All three ROS
      were produced in the presence of SWNT-COOH and molecular oxygen (3O2). 1O2
      production was confirmed by observing enhanced FFA decay in deuterium oxide,
      attenuated decay of FFA in the presence of azide ion, and the lack of decay of
      FFA in deoxygenated solutions. Photogeneration of O2.- and .OH was confirmed by
      applying superoxide dismutase (SOD) and tert-butanol assays, respectively. In air
      equilibrated suspensions, the loss of 0.2 mM FFA in 10 mg/L SWNT-COOH was
      approximately 85% after 74 h. Production of 1O2 was not dependent on pH from 7 to
      11; however photoinduced aggregation was observed at pH 3.

PMID- 20687544
TI  - Synthesis and in vitro evaluation of defined HPMA folate conjugates: influence of
      aggregation on folate receptor (FR) mediated cellular uptake.
AB  - In this article we report the synthesis and in vitro evaluation of well-defined,
      folate functionalized and fluorescently labeled polymers based on the clinically
      approved N-(2-hydroxypropyl)-methacrylamide (HPMA). The polymers were prepared
      applying the RAFT polymerization method as well as the reactive ester approach.
      The molecular weights of the polymers synthesized were around 15 and 30 kDa. The
      total content of conjugated folate varied from 0, 5, and 10 mol %. The cellular
      uptake of these polymers was investigated in the folate receptor (FR)-positive
      human nasopharyngeal epidermal carcinoma (KB-3-1) and FR-negative human lung
      epithelial carcinoma (A549) cancer cell lines. In FR-positive cells, the cellular
      uptake of polymers depended strongly on the folate content. The conjugates with
      the highest folate content led to the highest level of cell-associated
      fluorescence. Regarding influence of molecular weight, nonsignificant differences
      were observed when total cell uptake was analyzed. The cellular uptake is related
      to the aggregate formation of the polymer conjugates, which were studied by
      fluorescence correlation spectroscopy (FCS). For the conjugates, we found
      aggregates with a diameter ranging from 11-18 nm. Much to our surprise, we found
      aggregates of the same size for the 30 kDa polymer bearing 5 mol % folate and for
      the 15 and 30 kDa conjugates with a folate content of 10 mol %. Consequently, a
      different conformation in solution for the different conjugates was expected. By
      live cell confocal fluorescence microscopy the receptor-mediated endocytosis
      process was observed, as colocalization with lysosomal markers was achieved. In
      addition, cellular uptake was not observed in FR-negative cells (A549) and can be
      dramatically reduced by blocking the FR with free folic acid. Our findings
      clearly underline the need for a minimum amount of accessible folate units to
      target the FR that triggers specific cellular uptake. Furthermore, it has been
      demonstrated that the targeting vector itself strongly influences the aggregation
      behavior in solution and thus determines the interaction with cells regarding
      cellular uptake as well as intracellular localization.

PMID- 20687545
TI  - Impacts of an anti-androgen and an androgen/anti-androgen mixture on the
      metabolite profile of male fathead minnow urine.
AB  - Male and female fathead minnows (Pimephales promelas, FHM) were exposed via water
      to 20 or 200 microg/L of cyproterone acetate (CA), a model androgen receptor (AR)
      antagonist. FHM were also exposed to 500 ng/L of 17beta-trenbolone (TB), a model
      AR agonist, and to mixtures of TB with both concentrations of CA. The urine
      metabolite profile (as measured by 1H NMR spectroscopy) of male FHM exposed to
      the high concentration of CA was markedly different from that of controls, and
      this difference was less for males coexposed to the associated TB+CA mixture. The
      exposure to TB alone had almost no impact on the male urine profile. These
      results suggest that male FHM urinary metabolite profiling may be useful for
      directly detecting effects of anti-androgens. In contrast, the urinary profile of
      male FHM exposed to the lower concentration of CA was not very different from
      that of controls, but, unexpectedly, this difference was increased when coexposed
      to the associated TB+CA mixture. This suggests that TB with CA at the lower
      concentration impacts male FHM through an interactive effect possibly unrelated,
      or in addition, to AR antagonism. The relative occurrence of male-like nuptial
      tubercles in female FHM exposed to TB and to the mixtures of TB and CA supported
      the metabolomics data.

PMID- 20687546
TI  - Potassium(I) amidotrihydroborate: structure and hydrogen release.
AB  - Potassium(I) amidotrihydroborate (KNH(2)BH(3)) is a newly developed potential
      hydrogen storage material representing a completely different structural motif
      within the alkali metal amidotrihydroborate group. Evolution of 6.5 wt % hydrogen
      starting at temperatures as low as 80 degrees C is observed and shows a
      significant change in the hydrogen release profile, as compared to the
      corresponding lithium and sodium compounds. Here we describe the synthesis,
      structure, and hydrogen release characteristics of KNH(2)BH(3).

PMID- 20687547
TI  - Impact of micronization on rapidly digestible, slowly digestible, and resistant
      starch concentrations in normal, high-amylose, and waxy barley.
AB  - This study determined the effect of micronization (high intensity infrared
      heating) on the concentrations of rapidly digestible starch (RDS), slowly
      digestible starch (SDS), and resistant starch (RS) in normal barley (NB), high
      amylose barley (HAB), and waxy barley (WB). The gelatinized starch contents and
      the thermal properties of the micronized samples also were determined. Samples of
      each barley type were tempered to each of three moisture contents (approximately
      17, 31, or 41%), and then each tempered sample was micronized to each of three
      surface temperatures (100, 120, or 140 degrees C). Micronized barley samples were
      substantially lower in RS and in SDS and, therefore, higher in RDS than
      corresponding unprocessed samples. In general, higher concentrations of RDS and
      of gelatinized starch were associated with higher initial moisture contents and
      higher surface temperatures. The lowest concentrations of RS were observed in
      micronized WB samples. Similar concentrations of RS were observed in
      corresponding NB and HAB samples. Micronization resulted in slight increases in
      the onset (To), peak (Tp), and completion (Tc) gelatinization temperatures and in
      substantial reductions in the gelatinization enthalpy (DeltaH), the latter
      reflecting the levels of gelatinized starch in micronized samples, particularly
      in samples micronized at higher moisture contents and to higher surface
      temperatures. Endothermic transitions were evident only in samples tempered to
      17% moisture or 31% moisture (surface temperature of 100 degrees C only).

PMID- 20687548
TI  - Visible light sensitized inactivation of MS-2 bacteriophage by a cationic amine
      functionalized C60 derivative.
AB  - Recently, we reported the successful synthesis of various hexakis C60 derivatives
      (i.e., C60 with six functional groups containing NH3+-, CO2H-, or OH-terminals)
      with enhanced stability in water for aqueous phase application (Lee et al.,
      Environ. Sci. Technol. 2009, 43, pp 6604-6610). Among these newly synthesized C60
      derivatives, the cationic hexakis C60 derivative with amine functionality,
      C60(CR2)6 (R=CO2(CH2)2NH3+CF3CO2-), was found to exhibit remarkable efficiency to
      inactivate Escherichia coli and MS-2 bacteriophage under UVA irradiation. Herein,
      we report that this amine-functionalized C60 derivative is also photoactive in
      response to visible light from both commercial fluorescence lamps and sunlight.
      Efficient production of 1O2, facile reaction of 1O2 with proteins in MS-2 phage
      capsid and electrostatic attraction between positively charged C60 derivative and
      negatively charged MS-2 phage collectively contributed to high efficiency of MS-2
      phage inactivation in this photocatalytic disinfection system. The rate of 1O2
      production was evaluated using a probe compound, furfuryl alcohol, and 1O2 CT
      (the product of 1O2 concentration and exposure time) required to achieve a target
      level of virus inactivation was quantitatively analyzed. The unique visible-light
      sensitized virucidal property makes this C60 derivative highly desirable for the
      development of sustainable disinfection strategies that do not require continuous
      chemical addition nor an external energy source other than ambient light.

PMID- 20687549
TI  - Fabrication, mechanical properties, and biocompatibility of graphene-reinforced
      chitosan composites.
AB  - Few-layered graphene sheets, synthesized by direct current arc-discharge method
      using NH(3) as one of the buffer gases, were dispersed in chitosan/acetic acid
      solutions. FTIR and X-ray photoelectron spectroscopy showed the presence of
      oxygen-containing functional groups on the surface of graphene sheets that may
      assist the good dispersion of graphene in chitosan solution. Graphene/chitosan
      films were produced by solution casting method. The mechanical properties of
      composite films were tested by nanoindentation method. With the addition of a
      small amount of graphene in chitosan (0.1-0.3 wt %), the elastic modulus of
      chitosan increased over ~ 200%. The biocompatibility of graphene/chitosan
      composite films was checked by tetrazolium-based colorimetric assays in vitro.
      The cell adhesion result showed that the L929 cell can adhere to and develop on
      the graphene/chitosan composite films as well as on pure chitosan film,
      indicating that graphene/chitosan composites have good biocompatibility. Because
      there is no metallic impurity in graphene raw materials, the time-consuming
      purification process for removing metal nanoparticles entrapped in carbon
      nanotubes is thus avoided when graphene is used to prepare biomedical materials.
      Graphene/chitosan composites are potential candidates as scaffold materials in
      tissue engineering.

PMID- 20687550
TI  - Multiphase electrode microbial fuel cell system that simultaneously converts
      organics coexisting in water and sediment phases into electricity.
AB  - Our challenge in this study was to harvest electricity from organics coexisting
      in two different phases (water and sediment) in an organics-contaminated benthic
      environment and to obtain increased current using a multiphase electrode
      microbial fuel cell (multiphase MFC). The multiphase MFC consisted of a floating
      electrode (FE), a midelectrode (ME), and a sediment electrode (SE) with no other
      components. The SE was embedded in sediment; the FE and ME were then overlaid in
      the water surface layer and in the middle of the water column of an aquarium,
      respectively. During continuous supply of organics at a COD loading rate of 94 mg
      of COD L(-1) day(-1) and after the cessation of organics being supplied at COD
      loading rates of 330 and 188 mg of COD L(-1) day(-1), the multiphase MFC showed
      the highest current production, as compared to the control MFCs [a floating-type
      MFC (FT-MFC) and two types of sediment MFCs (SMFC-A and SMFC-B)]. The total
      charges (in coulombs) of the multiphase MFC integrated from the currents,
      obtained under the three operating conditions mentioned above, were comparable to
      the sums of charges for the FT-MFC and SMFC. As a result, this study found that
      the multiphase MFC can (1) utilize organics in the sediment similarly to SMFCs,
      (2) use organics in the water phase similarly to FT-MFCs, and (3) obtain
      increased current analogous to the sum of an SMFC and a FT-MFC. Thus, it is
      thought that the multiphase MFC developed in this work could be suitable for use
      in water bodies being continuously or frequently contaminated with organic waste.

PMID- 20687551
TI  - Synthesis of quaternary carbon centers via hydroformylation.
AB  - The application of hydroformylation to the synthesis of quaternary carbon centers
      is reported. The synthesis of the highly substituted carbon is achieved by
      applying a catalytic amount of 1. Ligand 1 serves as a catalytic directing group
      by covalently and reversibly binding to both the substrate and catalyst. The
      intramolecular nature of the directing group strategy accelerates the
      hydroformylation reaction such that the reaction is performed at mild
      temperatures (35-55 degrees C) and with excellent regioselectivity (b:l > 94:6).

PMID- 20687553
TI  - Medicinal mushroom Ganoderma lucidum as a potent elicitor in production of t
      resveratrol and t-piceatannol in peanut calluses.
AB  - Phytoalexins t-resveratrol and t-piceatannol, the well-known health-promoting
      active components in plants, are secondary metabolites generated upon biotic or
      abiotic stresses. We have reported UV-irradiated peanut callus is a potent means
      to produce these compounds (J. Agric. Food Chem. 2005, 53, 3877). In this work,
      the effects of fungi and chemical elicitors on induction of t-resveratrol and t
      piceatannol were examined. Results showed the investigated fungi Botryodiplodia
      theobromae and Reishi Ganoderma lucidum were generally more effective than
      chemical stress methyl jasmonate, salicylic acid, and sucrose. As high as 15.46+/
      9.85 microg of t-resveratrol and 6.93+/-2.03 microg of t-piceatannol could be
      elicited in each gram of callus by sterilized G. lucidum mycelium (80 mg).
      Although much more sterilized G. ludicum mycelia was required to induce similar
      level of t-resveratrol and t-piceatannol in comparison to the sterilized B.
      theobromae mycelia (1 mg), uptake of the G. ludicum mycelium may provide a
      variety of health-promoting effects. Our findings suggest G. ludicum mycelium
      treated peanut callus is a good source of bioactive components.

PMID- 20687552
TI  - Enzymatic synthesis and characterization of hydroquinone galactoside using
      Kluyveromyces lactis lactase.
AB  - Hydroquinone galactoside (HQ-Gal) as a potential skin whitening agent was
      synthesized by the reaction of lactase (beta-galactosidase) from Kluyveromyces
      lactis, Aspergillus oryzae, Bacillus circulans, and Thermus sp. with lactose as a
      donor and HQ as an acceptor. Among these lactases, the acceptor reaction
      involving HQ and lactose with K. lactis lactase showed a higher conversion ratio
      to HQ-Gal (60.27%). HQ-Gal was purified using butanol partitioning and silica gel
      column chromatography. The structure of the purified HQ-Gal was determined by
      nuclear magnetic resonance, and the ionic product was observed at m/z 295
      (C12H16O7Na)+ using matrix assisted laser desorption ionization time-of-flight
      mass spectrometry. HQ-Gal was identified as 4-hydroxyphenyl-beta-d
      galactopyranoside. The optimum conditions for HQ-Gal synthesis by K. lactis
      determined using response surface methodology were 50 mM HQ, 60 mM lactose, and
      20 U mL(-1) lactase. These conditions produced a yield of 2.01 g L(-1) HQ-Gal.
      The half maximal inhibitory concentration (IC50) of diphenylpicrylhydrazyl
      scavenging activity was 3.31 mM, indicating a similar antioxidant activity
      compared to beta-arbutin (IC50=3.95 mM). The Ki value of HQ-Gal (0.75 mM) against
      tyrosinase was smaller than that of beta-arbutin (Ki=1.97 mM), indicating its
      superiority as an inhibitor. HQ-Gal inhibited (23%) melanin synthesis without
      being significantly toxic to the cells, while beta-arbutin exhibited only 8%
      reduction of melanin synthesis in B16 melanoma cells compared with the control.
      These results indicate that HQ-Gal may be a suitable functional component in the
      cosmetics industry.

PMID- 20687554
TI  - Catalytic asymmetric Claisen rearrangement of unactivated allyl vinyl ethers.
AB  - Nearly a century after their original discovery, catalyzed enantioselective
      variants of the venerable Claisen rearrangement remain relatively rare. We have
      discovered a cooperative transition metal-Lewis acid cocatalyst system that
      affects highly enantio- and diastereoselective examples of archetypical Claisen
      rearrangements. The catalyzed rearrangements proceed using an easily prepared
      enantioenriched transition metal catalyst and a commercially available Lewis acid
      cocatalyst at ambient temperature in common solvents.

PMID- 20687555
TI  - Experimental and computational study of a direct O2-coupled Wacker oxidation:
      water dependence in the absence of Cu salts.
AB  - The kinetics of the Pd[(-)-sparteine]Cl(2) catalyzed oxidation of decene using
      oxygen as the sole oxidant have been studied in the absence of copper salts and
      high [Cl(-)]. Saturation kinetics are observed for [decene] as well as a third
      order dependence on [water]. A mechanism is proposed involving the dissociation
      of two chlorides and rate-limiting formation of a three-water hydrogen bridged
      network and subsequent oxypalladation as supported by computational studies.

PMID- 20687556
TI  - Formic acid acting as an efficient oxygen scavenger in four-electron reduction of
      oxygen catalyzed by a heterodinuclear iridium-ruthenium complex in water.
AB  - A heterodinuclear iridium-ruthenium complex
      [Ir(III)(Cp*)(H(2)O)(bpm)Ru(II)(bpy)(2)](SO(4))(2) (Cp* = eta(5)-pentamethyl
      cyclopentadienyl, bpm = 2,2'-bipyrimidine, bpy = 2,2'-bipyridine) acts as an
      effective catalyst for removal of dissolved O(2) by the four-electron reduction
      of O(2) with formic acid in water at an ambient temperature.

PMID- 20687557
TI  - An opportunity for Mg-catalyzed Grignard-type reactions: direct coupling of
      benzylic halides with pinacolborane with 10 mol % of magnesium.
AB  - Mg in catalytic amounts as the only metal permits the reductive coupling between
      benzyl halides and pinacolborane. HBpin acts both as an electrophile and as a
      reducing agent to regenerate an organomagnesium species in situ. An hydride
      oxidation mechanism is proposed on the basis of DFT calculations.

PMID- 20687558
TI  - Automatic assignment of the intrinsically disordered protein Tau with 441
      residues.
AB  - Intrinsically disordered proteins carry out many important functions in the cell.
      However, the lack of an ordered structure causes dramatic signal overlap and
      complicates the NMR-based characterization of their structure and dynamics. Here
      we demonstrate that the resonance assignment of 441-residue Tau and its smaller
      isoforms, htau24 (383 residues) and htau23 (352 residues), three prototypes of
      intrinsically disordered proteins, which bind to microtubules and play a key role
      in Alzheimer disease, can be obtained within 5 days by a combination of seven
      dimensional NMR spectra with optimized methods for automatic assignment. Chemical
      shift differences between the three isoforms provide evidence for the global
      folding of Tau in solution.

PMID- 20687559
TI  - Characterization of volatile constituents in commercial oak wood chips.
AB  - The volatile composition of the different oak wood pieces (chips of Quercus spp.)
      that can be found on the market to be used as alternatives to barrels for aging
      wines, as well as of chips of Quercus pyrenaica which are being introduced, was
      studied, evaluating the contents of volatile phenols, lactones, furanic
      compounds, pyranones, phenolic aldehydes, phenolic ketones, and others. In regard
      to the overall results, the volatile composition of these products varies widely
      and has not been clearly laid out according to either the oak species or the wood
      toasting intensity. Taking into account that the different characteristics of
      alternatives to barrel products are reflected in the wine treated with them and
      that an oenological profile based on these variables (origin and toasting level)
      cannot be defined, only an appropriate chemical analysis would reveal the quality
      of alternative-to-barrel products and allow us to attempt to foresee its effects
      on the chemical and organoleptic characteristics of the wines treated with them.
      On the other hand, the Q. pyrenaica alternative products are very similar to
      those of other species, with some aromatic particularities, such as their high
      levels of furanic compounds, eugenol, Furaneol, and cis-whiskylactone, and low
      levels of vanillin.

PMID- 20687560
TI  - Degradation of the Alternaria mycotoxins alternariol, alternariol monomethyl
      ether, and altenuene upon bread baking.
AB  - The stability of the Alternaria mycotoxins alternariol, alternariol monomethyl
      ether, and altenuene upon bread baking was investigated by model experiments
      using a spiked wholemeal wheat flour matrix. For alternariol and alternariol
      monomethyl ether, but not for altenuene, degradation products, formed through a
      sequence of hydrolysis and decarboxylation, could be identified in pilot studies.
      The simultaneous quantification of alternariol, alternariol monomethyl ether,
      altenuene, and the degradation products was achieved by a newly developed high
      performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS)
      multimethod. The obtained quantitative data indicate that the Alternaria
      mycotoxins are barely degraded during wet baking, while significant degradation
      occurs upon dry baking, with the stability decreasing in the order alternariol
      monomethyl ether>alternariol>altenuene. The novel degradation products could be
      detected after the wet baking of flour spiked with alternariol and in a sample
      survey of 24 commercial cereal based baking products.

PMID- 20687561
TI  - Fluxionality of [(Ph3P)3M(X)] (M = Rh, Ir). The red and orange forms of
      [(Ph3P)3Ir(Cl)]. Which phosphine dissociates faster from Wilkinson's catalyst?
AB  - NMR studies of intramolecular exchange in [(Ph(3)P)(3)Rh(X)] (X = CF(3), CH(3),
      H, Ph, Cl) have produced full sets of activation parameters for X = CH(3) (E(a) =
      16.4 +/- 0.6 kcal mol(-1), DeltaH(double dagger) = 16.0 +/- 0.6 kcal mol(-1), and
      DeltaS(double dagger) = 12.7 +/- 2.5 eu), H (E(a) = 10.7 +/- 0.2 kcal mol(-1),
      DeltaH(double dagger) = 10.3 +/- 0.2 kcal mol(-1), and DeltaS(double dagger) = 
      7.2 +/- 0.8 eu), and Cl (E(a) = 16.3 +/- 0.2 kcal mol(-1), DeltaH(double dagger)
      = 15.7 +/- 0.2 kcal mol(-1), and DeltaS(double dagger) = -0.8 +/- 0.8 eu).
      Computational studies have shown that for strong trans influence ligands (X = H,
      Me, Ph, CF(3)), the rearrangement occurs via a near-trigonal transition state
      that is made more accessible by bulkier ligands and strongly donating X. The
      exceedingly fast exchange in novel [(Ph(3)P)(3)Rh(CF(3))] (12.1 s(-1) at -100
      degrees C) is due to strong electron donation from the CF(3) ligand to Rh, as
      demonstrated by computed charge distributions. For weaker donors X, this
      transition state is insufficiently stabilized, and hence intramolecular exchange
      in [(Ph(3)P)(3)Rh(Cl)] proceeds via a different, spin-crossover mechanism
      involving triplet, distorted-tetrahedral [(Ph(3)P)(3)Rh(Cl)] as an intermediate.
      Simultaneous intermolecular exchange of [(Ph(3)P)(3)Rh(Cl)] with free PPh(3)
      (THF) via a dissociative mechanism occurs exclusively from the sites cis to Cl
      (E(a) = 19.0 +/- 0.3 kcal mol(-1), DeltaH(double dagger) = 18.5 +/- 0.3 kcal mol(
      1), and DeltaS(double dagger) = 4.4 +/- 0.9 eu). Similar exchange processes are
      much slower for [(Ph(3)P)(3)Ir(Cl)] which has been found to exist in orange and
      red crystallographic forms isostructural with those of [(Ph(3)P)(3)Rh(Cl)].

PMID- 20687562
TI  - Isolation of cellulase-producing bacteria and characterization of the cellulase
      from the isolated bacterium Cellulomonas sp. YJ5.
AB  - A cellulase-producing bacterium was isolated from soil and identified as
      Cellulomonas sp. YJ5. Maximal cellulase activity was obtained after 48 h of
      incubation at 30 degrees C in a medium containing 1.0% carboxymethyl cellulose
      (CMC), 1.0% algae powder, 1.0% peptone, 0.24% (NH4)2SO4, 0.20% K2HPO4, and 0.03%
      MgSO(4).7H2O. The cellulase was purified after Sephacryl S-100 chromatography
      twice with a recovery of 27.9% and purification fold of 17.5. It was, with N
      terminal amino acids of AGTKTPVAK, stable at pH 7.5-10.5 and 20-50 degrees C with
      optimal pH and temperature of 7.0 and 60 degrees C, respectively. Cu2+, Fe2+,
      Hg2+, Cr3+, and SDS highly inhibited, but cysteine and beta-mercaptoethanol
      activated, its activity. Substrate specificity indicated it to be an endo-beta
      1,4-glucanase.

PMID- 20687563
TI  - Linear and branched poly(omega-hydroxyacid) esters in plant cutins.
AB  - Poly(omega-hydroxyacid) ester oligomers were obtained from the cutin of four
      plant cuticles by partial depolymerization methanolysis. The structure of these
      oligomers was determined by electrospray ionization coupled to tandem mass
      spectrometry (ESI-MS/MS) analysis of their lithium-adducts, showing which
      monomers were present and their relative position. Dimers up to heptamers were
      identified, in a total yield of oligomers of up to 50% of the total cutin
      content. Two main structural types of poly(omega-hydroxyacid) ester oligomers
      were found. Poly(10,16-dihydroxyhexadecanoic acid) esters were the main oligomers
      in the cutin of Lycopersicum esculentum fruit, with a predominantly branched
      structure. The 1D and 2D NMR analysis of these oligomers showed that inter
      monomer linkages were mostly in secondary midchain hydroxyls, in a ratio of 4.5
      to 1, compared with esterification in the primary omega-hydroxyls. In Hedera
      helix leaves cutin, poly(9-epoxy-18-hydroxyoctadecanoic acid) esters were the
      dominant oligomers, composed of monomers linearly linked head-to-tail. It is
      proposed that the cutin polyesters have different poly(omega-hydroxyacid)ester
      domains, either built of linear chains, where the C18-epoxy omega-hydroxyacids
      are dominant, or forming a highly branched network, where the C16-dihydroxy omega
      hydroxyacids predominate. It is hypothesized that the C18 linear polyester can
      account for the ordered lamellae seen at ultrastructural level in H. helix
      cuticle, and that the C16 mostly branched polyester will be the basis of the
      reticulate structure seen in L. esculentum cuticle.

PMID- 20687564
TI  - Phenolic compounds in chestnut (Castanea sativa Mill.) heartwood. Effect of
      toasting at cooperage.
AB  - The phenolic and tannic composition of heartwood extracts from Castanea sativa
      Mill., before and after toasting in cooperage, were studied using HPLC-DAD and
      HPLC-DAD/ESI-MS, and some low molecular weight phenolic compounds and
      hydrolyzable tannins were found. The low molecular weight phenolic compounds were
      lignin constituents as the acids gallic, protocatechuic, vanillic, syringic,
      ferulic, and ellagic, the aldehydes protocatechuic, vanillic, syringic,
      coniferylic, and sinapic, and the coumarin scopoletin. Their patterns were
      somewhat different those of oak because oak does not contain compounds such
      protocatechuic acid and aldehyde and is composed of much lower amounts of gallic
      acid than chestnut. Vescalagin and castalagin were the main ellagitannins, and
      acutissimin was tentatively identified for the first time in this wood. Moreover,
      some gallotannins were tentatively identified, including different isomers of di,
      tri, tetra, and pentagalloyl glucopyranose, and di and trigalloyl
      hexahydroxydiphenoyl glucopyranose, comprising 20 different compounds, as well as
      some ellagic derivatives such as ellagic acid deoxyhexose, ellagic acid dimer
      dehydrated, and valoneic acid dilactone. These ellagic derivatives as well as
      some galloyl and hexahydroxydiphenoyl derivatives were tentatively identified for
      the first time in this wood. The profile of tannins was therefore different from
      that of oak wood because oak only contains tannins of the ellagitannins type.
      Seasoned and toasted chestnut wood showed a very different balance between lignin
      derivatives and tannins because toasting resulted in the degradation of tannins
      and the formation of low molecular weight phenolic compounds from lignin
      degradation. Moreover, the different toasting levels provoked different balances
      between tannins and lignin constituents because the intensity of lignin and
      tannin degradation was in relation to the intensity of toasting.

PMID- 20687565
TI  - Proteomic evaluation of chicken brush-border membrane during the early posthatch
      period.
AB  - The chicken small intestine undergoes structural and functional changes during
      the early posthatch period to accommodate the transition from a lipid-rich diet
      inside the egg to a carbohydrate- and protein-based diet. Many of the enterocyte
      brush-border membrane-associated proteins responsible for mediating changes in
      nutrient utilization are unknown. The objective of this study was to conduct a
      proteomic analysis of chicken small intestine during the early posthatch period.
      We isolated brush-border membrane at day of hatch and days 1, 3, 7, and 14
      posthatch from the small intestine of 2 genetic lines of broilers that differ in
      growth performance, and performed 2D gel-electrophoresis. A total of 1693 spots
      were analyzed by matrix-assisted laser desorption/ionization-tandem time-of
      flight mass spectrometry (MALDI-TOF/TOF). In total, 132 different proteins were
      identified and grouped according to biological function. Of these, there were 10
      nutrient transporters, 9 digestive enzymes, and 17 proteins associated with
      cytoskeletal structure and microvilli organization. The remaining proteins were
      classified as basolateral membrane (3), endosomal/membrane trafficking (8),
      signaling (14), metabolic (33), degradative (5), stress-related (5), protein
      synthesis machinery/mitochondria/nucleus (19), immunologic (1), or unknown (8).
      Of the spots in which proteins were identified, there were 10 that showed an
      effect of broiler genetic line on protein spot density (P<0.001) and 19 spots
      showing a correlation of broiler genetic line x age (P<0.001). Identification of
      brush-border membrane-associated proteins is an important step in furthering our
      understanding of digestion and absorption in the chicken.

PMID- 20687566
TI  - Tunable photocatalytic selectivity of hollow TiO2 microspheres composed of
      anatase polyhedra with exposed {001} facets.
AB  - A fluoride mediated self-transformation method is proposed for the synthesis of
      hollow TiO(2) microspheres (HTS) composed of anatase polyhedra with exposed ca.
      20% {001} facets. Importantly, HTS exhibit tunable photocatalytic selectivity in
      decomposing azo dyes in water. The fluorinated HTS show preferential
      decomposition of methyl orange (MO) in comparison to methylene blue (MB). In
      contrast, the surface-modified HTS by either NaOH washing or calcinations at 600
      degrees C favor decomposition of MB over MO. The surface chemistry and the
      surface structure at the atomic level are key factors in tuning the adsorption
      selectivity and, consequently, photocatalytic selectivity of HTS toward azo dyes.

PMID- 20687567
TI  - Secretome analysis of multiple pancreatic cancer cell lines reveals perturbations
      of key functional networks.
AB  - The cancer secretome is a rich repository in which to mine useful information for
      both cancer biology and clinical oncology. To help understand the mechanisms
      underlying the progression of pancreatic cancer, we characterized the secretomes
      of four human pancreatic ductal adenocarcinoma (PDAC) cell lines versus a normal
      counterpart. To this end, we used a proteomic workflow based on high-confidence
      protein identification by mass spectrometry, semiquantitation by a label-free
      approach, and network enrichment analysis by a system biology tool. Functional
      networks significantly enriched with PDAC-dysregulated proteins included not only
      expected alterations within key mechanisms known to be relevant for tumor
      progression (e.g., cell-cell/cell-matrix adhesion, extracellular matrix
      remodeling, and cytoskeleton rearrangement), but also other extensive,
      coordinated perturbations never observed in pancreatic cancer. In particular, we
      highlighted perturbations possibly favoring tumor progression through immune
      escape (i.e., inhibition of the complement system, deficiency of selected
      proteasome components within the antigen-presentation machinery, and inhibition
      of T cell cytoxicity), and a defective protein folding machinery. Among the
      proteins found concordantly oversecreted in all of our PDAC cell lines, many are
      reportedly overexpressed in pancreatic cancer (e.g., CD9 and Vimentin), while
      others (PLOD3, SH3L3, PCBP1, and SFRS1) represent novel PDAC-secreted proteins
      that may be worth investigating.

PMID- 20687568
TI  - Photoinduced kinetics of SERS in bioinorganic hybrid systems. a case study:
      dopamine-TiO2.
AB  - The reported observation of SERS on semiconductors has confirmed the feasibility
      of distinguishing the charge-transfer mechanism from the electromagnetic one
      responsible for the enhancement of the signal in metal nanoparticles.
      Experimental investigation of the well characterized dopamine-TiO(2) system
      revealed an unexpected dependence on coverage and size. We propose here a
      theoretical model applicable to SERS on semiconducting substrates that explains
      this remarkable behavior. The model is based on a competition mechanism arising
      from the formation of an electron gas in the conduction band of the semiconductor
      due to the photoexcitation of a charge-transfer complex. Taking into account the
      two competing effects, a linear increase in the Raman intensity arising from
      increasing coverage and a quenching effect due to the photon absorption by the
      electron gas, provides excellent agreement between our model and the experiment
      for 5 nm nanoparticles. Discrepancies for the case of 2 nm nanoparticles are
      attributed to quantum confinement, an effect that is investigated elsewhere.

PMID- 20687569
TI  - Adsorption of nonionic surfactant on silica nanoparticles: structure and
      resultant interparticle interactions.
AB  - Addition of nonionic surfactant, C(12)E(9), to an aqueous dispersion of charge
      stabilized silica nanoparticles renders particle aggregation reversible. In
      contrast, aggregation of the same silica particles in aqueous solutions is
      irreversible. We use a combination of small-angle X-ray scattering (SAXS) and
      contrast matching small-angle neutron scattering (SANS) to investigate
      interparticle interactions and microstructure in dispersions of silica particles
      in aqueous nonionic surfactant solutions. We show that the silica particles
      interact through a screened Coulombic interaction in aqueous dispersions;
      interestingly, this interparticle interaction is hard-sphere-like in surfactant
      solutions. In surfactant solutions, we show that the final surfactant-particle
      structure can be modeled as 14 micelles adsorbed (on average) on the surface of
      each silica particle. This gives rise to the short-range interparticle repulsion
      that makes particle aggregation reversible, and results in the hard sphere
      interparticle interaction potential. Finally, we show that adsorption of
      polyethylene imine on the surface of the silica particles prevents adsorption of
      surfactant micelles on the particle surface.

PMID- 20687570
TI  - Hexagonal close-packed structure of au nanocatalysts solidified after ge nanowire
      vapor-liquid-solid growth.
AB  - We report that approximately 10% of the Au catalysts that crystallize at the tips
      of Ge nanowires following growth have the close-packed hexagonal crystal
      structure rather than the equilibrium face-centered-cubic structure. Transmission
      electron microscopy results using aberration-corrected imaging, and diffraction
      and compositional analyses, confirm the hexagonal phase in these 40-50 nm
      particles. Reports of hexagonal close packing in Au, even in nanoparticle form,
      are rare, and the observations suggest metastable pathways for the
      crystallization process. These results bring new considerations to the
      stabilization of the liquid eutectic alloy at low temperatures that allows for
      vapor-liquid-solid growth of high quality, epitaxial Ge nanowires below the
      eutectic temperature.

PMID- 20687571
TI  - Influence of disulfide connectivity, electrostatics, and hydrophobicity on the
      conformational variations of alpha-conotoxin GI single-disulfide analogues:
      simulations with polarizable force field.
AB  - The roles of the disulfide bridge, electrostatics, and hydrophobic/hydrophilic
      effects in the structural stability and conformational changes of six single
      disulfide analogues of alpha-conotoxin GI(2-7;3-13) in aqueous solution are
      investigated by using molecular dynamics simulations with a fragment-based
      polarization model (J. Phys. Chem. A 2008, 112, 9854.). It is found that the
      relative stabilities are largely determined by the dipole-dipole interactions
      between secondary structure-based fragments, revealing the favorable effect of
      polar residues on conformational stabilities. The loop size closely correlates to
      not only the thermodynamic stability but also the local geometry of disulfide
      bridge. The disulfide loops with no more than five residues [GI(2-7), GI(3-7),
      and GI(7-13)] choose the left-handed disulfide conformation, while the larger
      loops [with nine and 10 residues in GI(3-13) and GI(2-13)] and a smaller
      disulfide loop [GI(2-3) without intercysteine residue] prefer the right-handed
      configuration. In the left-handed analogues, the dihedral angles concerning
      disulfide bonds decrease subtly along with the enlargement of disulfide loops. A
      converse dihedral angle and loop size relationship is found in the right-handed
      isomers. These results are rationalized by the strain energy of the disulfide
      bond as well as the electrostatic and van der Waals interactions between cysteine
      pairs. The single-disulfide analogues also exhibit much higher conformational
      diversity than the native GI. The important role of the size of hydrophobic core
      in the conformational evolution is also demonstrated in terms of the radius of
      gyration of the hydrophobic region. The radial distribution functions show the
      significant solvent-solute hydrogen bonding, implying that the interplay between
      the intermolecular and the intramolecular interactions control the dynamic
      process of GI single-disulfide analogues.

PMID- 20687572
TI  - Molecular dynamics simulations of CO2 at an ionic liquid interface: adsorption,
      ordering, and interfacial crossing.
AB  - The ionic liquid-CO(2) system is of interest because ionic liquids have potential
      to be used for CO(2) capture. Using classical molecular dynamics simulations, the
      vacuum-liquid and CO(2) gas-liquid interfaces of the ionic liquid 1-n-butyl-3
      methylimidazolium bis(trifluoromethylsulfonyl)imide ([bmim][Tf(2)N]) have been
      studied at a range of temperatures and pressures. Interfacial ordering and
      orientational tendencies of the ionic liquid at the vacuum interface generally
      agree with previous experimental and simulation studies. The interfacial
      structure of the IL remains relatively unperturbed when the liquid is in contact
      with CO(2). CO(2) adsorbs rapidly onto the liquid interface, forming a dense
      layer. Diffusion into the bulk occurs on a much slower time scale. Interfacial
      fluxes and diffusivities were determined. The potential of mean force for
      interfacial crossing and corresponding residence time distributions of
      interfacial crossing events of CO(2) were also calculated. CO(2) desorption from
      the liquid was also simulated. A high density CO(2) layer forms for desorption
      with CO(2) present but not for desorption into a vacuum. The interfacial behavior
      and transport dynamics have been characterized by studying these properties.

PMID- 20687573
TI  - Domino carbopalladation-carbonylation: generating quaternary stereocenters while
      controlling beta-hydride elimination.
AB  - A domino carbopalladation-carbonylation sequence for substrates possessing beta
      hydrogens is explored. This allows for the construction of complex architectures
      with vicinal stereocenters in a concise and rapid fashion via the
      stereocontrolled formation of two carbon-carbon bonds. An integral aspect of this
      domino reaction is the ability to control beta-hydride elimination of the
      organopalladium intermediate and instead form the carbonylation product.

PMID- 20687574
TI  - Pd-catalyzed carbonylative conjugate addition of dialkylzinc reagents to
      unsaturated carbonyls.
AB  - The Pd-catalyzed addition of organozinc reagents to unsaturated carbonyls in the
      presence of carbon monoxide provides 1,4-diketones in good yield. The reaction
      was studied with a number of substituted cyclic and acyclic ketones as well as
      alpha,beta-unsaturated aldehydes.

PMID- 20687575
TI  - Bovine serum albumin-catalyzed deprotonation of [1-(13)C]glycolaldehyde: protein
      reactivity toward deprotonation of the alpha-hydroxy alpha-carbonyl carbon.
AB  - Bovine serum albumin (BSA) in D(2)O at 25 degrees C and pD 7.0 was found to
      catalyze the deuterium exchange reactions of [1-(13)C]glycolaldehyde ([1
      (13)C]GA) to form [1-(13)C,2-(2)H]GA and [1-(13)C,2,2-di-(2)H]GA. The formation
      of [1-(13)C,2-(2)H]GA and [1-(13)C,2,2-di-(2)H]GA in a total yield of 51 +/- 3%
      was observed at early reaction times, and at later times, [1-(13)C,2-(2)H]GA was
      found to undergo BSA-catalyzed conversion to [1-(13)C,2,2-di-(2)H]GA. The overall
      second-order rate constant for these deuterium exchange reactions [(k(E))(P)]
      equals 0.25 M(-1) s(-1). By comparison, (k(E))(P) values of 0.04 M(-1) s(-1) [Go,
      M. K., Amyes, T. L., and Richard, J. P. (2009) Biochemistry 48, 5769-5778] and
      0.06 M(-1) s(-1) [Go, M. K., Koudelka, A., Amyes, T. L., and Richard, J. P.
      (2010) Biochemistry 49, 5377-5389] have been determined for the wild-type- and
      K12G mutant TIM-catalyzed deuterium exchange reactions of [1-(13)C]GA,
      respectively, to form [1-(13)C,2,2-di-(2)H]GA. These data show that TIM and BSA
      exhibit a modest catalytic activity toward deprotonation of the alpha-hydroxy
      alpha-carbonyl carbon. We suggest that this activity is intrinsic to many
      globular proteins, and that it must be enhanced to demonstrate meaningful de novo
      design of protein catalysts of proton transfer at alpha-carbonyl carbon.

PMID- 20687576
TI  - Universal surfactant for water, oils, and CO2.
AB  - A trichain anionic surfactant sodium 1,4-bis(neopentyloxy)-3
      (neopentyloxycarbonyl)-1,4-dioxobutane-2-sulfonate (TC14) is shown to aggregate
      in three different types of solvent: water, heptane, and liquid CO(2). Small
      angle neutron scattering (SANS) has been used to characterize the surfactant
      aggregates in water, heptane, and dense CO(2). Surface tension measurements, and
      analyses, show that the addition of a third branched chain to the surfactant
      structural template is critical for sufficiently lowering the surface energy,
      tipping the balance between a CO(2)-incompatible surfactant (AOT) and CO(2)
      philic compounds that will aggregate to form micelles in dense CO(2) (TC14).
      These results highlight TC14 as one of the most adaptable and useful surfactants
      discovered to date, being compatible with a wide range of solvent types from high
      dielectric polar solvent water to alkanes with low dielectrics and even being
      active in the uncooperative and challenging solvent environment of liquid CO(2).

PMID- 20687577
TI  - Cobalt nanoparticle Langmuir-Schaefer films on ethylene glycol subphase.
AB  - The Langmuir-Schaefer (LS) technique was applied to prepare two-dimensional films
      of tridodecylamine (TDA)-stabilized Co nanoparticles. Ethylene glycol was used as
      the subphase because the Co nanoparticles spread better on it than on water.
      Surface pressure-area isotherms provided very little information on the floating
      films, and Brewster angle microscopy (BAM) was needed to characterize the film
      formation in situ. In addition to the subphase, various other experimental
      factors were tested in the LS film preparation, including solvent and presence of
      free TDA ligands and poly(styrene-b-ethylene oxide) (PS-b-PEO) in the
      nanoparticle dispersion. LS films deposited from dispersions from which the
      excess TDA ligands had been removed by washing the Co nanoparticles with 2
      propanol consisted of hexagonally organized particles in rafts that were
      organized in necklace structures. The addition of PS-b-PEO to the deposition
      dispersion resulted in small nanoparticle rafts evenly distributed over the
      substrate surface. The best Co-nanoparticle-PS-b-PEO films were obtained with a
      mass ratio of 20:1 between Co (9 nm) and block copolymer (38 200 g/mol, PEO
      content 22 mass %). These films were successfully transferred onto Formvar-coated
      TEM grids and characterized by transmission electron microscopy (TEM) and a
      superconducting quantum interference device (SQUID) magnetometer. At room
      temperature the films showed superparamagnetic behavior with a saturation
      magnetization M(s) of 100 emu/g (Co). Our work indicates that it is possible to
      obtain thin superparamagnetic LS films of TDA-stabilized Co nanoparticles. This
      is an important result as the TDA-stabilized Co nanoparticles show a very good
      resistance to corrosion.

PMID- 20687579
TI  - Adsorption of poly(ethylene oxide) at the free water surface. A computer
      simulation study.
AB  - Molecular dynamics simulation of poly(ethylene oxide) (PEO) adsorbed at the free
      water surface are reported on the canonical ensemble at 298 K. The obtained
      results are analyzed in terms of the novel Identification of the Truly
      Interfacial Molecules (ITIM) method. To obtain a deep, molecular level insight
      into the origin of the adsorption process, structural, dynamical, and energetic
      aspects have been investigated. It is found that the vast majority, i.e., 82%, of
      the monomer units of PEO are immersed into the bulk liquid phase, 17% of them are
      anchored right at the liquid-vapor interface, while 1% of them penetrate into the
      vapor phase. Although the presence of a few monomer units in the vapor phase is
      clearly demonstrated, the average lifetime of these monomer units is found to be
      rather small, i.e., 3.1 ps, and they are found not to move far from the surface
      as their interaction energy with the water molecules is still not negligible. The
      partition of the monomer units between the bulk liquid phase, interface, and
      vapor phase is determined by the delicate interplay of entropic and energetic
      factors, mostly by the requirements of maximizing the configurational entropy of
      the polymeric chain and minimizing the interfacial energy surplus.

PMID- 20687578
TI  - Allylation of nitrosobenzene with pinacol allylboronates. A regioselective
      complement to peroxide oxidation.
AB  - Addition of nitrosobenzene to pinacol allylboronates leads to oxidation of the
      organoboron with concomitant rearrangement of the substrate alkene. This reaction
      appears to proceed by allylboration of the nitroso group in analogy to carbonyl
      and imine allylation reactions. Remarkably, the N-O bond is cleaved during the
      reaction such that simple alcohols are the final reaction product.

PMID- 20687580
TI  - Precision patterning with luminescent nanocrystal-functionalized beads.
AB  - A reliable strategy is presented to combine the preparation of functional
      building blocks based on polymer beads decorated with luminescent nanocrystals
      (NCs) and their precise positioning onto suitable patterns by capillary assembly
      technique. In particular, a layer-by-layer (LbL) polyelectrolyte (PE) deposition
      procedure has been implemented to provide uniform NC coverage on PS beads, thus
      conveying the optical properties of luminescent nanocrystals to highly
      processable PS beads. The latter have then been integrated into patterned stamps
      by means of template-driven capillary assembly. Their selective positioning has
      been directed by means of pattern geometry. The use of luminescent (CdSe)ZnS NCs
      offers a direct optical probe to evaluate the efficiency of the positioning
      procedure on the substrate, enabling the extension of the method to a wide range
      of materials, i.e., NCs with different compositions and specific geometry
      dependent properties. Moreover, the precise control over the pattern geometry and
      the micrometer accuracy in positioning achieved by capillary assembly make such
      functional patterned structures excellent candidates for integration into devices
      exploiting specific size-dependent NC properties.

PMID- 20687581
TI  - Differentiating mechanistic possibilities for the thermal, intramolecular [2 + 2]
      cycloaddition of allene-ynes.
AB  - Intramolecular [2 + 2] cycloaddition reactions of allene-ynes offer a quick and
      efficient route to fused bicyclic ring structures. Insights into the mechanism
      and regiochemical preferences of this reaction are provided herein on the basis
      of the results of quantum chemical calculations (B3LYP/6-31+G(d,p)) and select
      experiments; both indicate that the reaction likely proceeds through a stepwise
      diradical pathway where one radical center is stabilized through allylic
      delocalization. The influences of the length of the tether connecting the alkyne
      and allene and substituent effects are also discussed.

PMID- 20687582
TI  - Site-specific proteomics approach for study protein S-nitrosylation.
AB  - Here we present a novel and robust method for the identification of protein S
      nitrosylation sites in complex protein mixtures. The approach utilizes the
      cysteinyl affinity resin to selectively enrich S-nitrosylated peptides reduced by
      ascorbate followed by nanoscale liquid chromatography tandem mass spectrometry.
      Two alkylation agents with different added masses were employed to differentiate
      the S-nitrosylation sites from the non-S-nitrosylation sites. We applied this
      approach to MDA-MB-231 cells treated with Angeli's salt, a nitric oxide donor
      that has been shown to inhibit breast tumor growth and angiogenesis. A total of
      162 S-nitrosylation sites were identified and an S-nitrosylation motif was
      revealed in our study. The 162 sites are significantly more than the number
      reported by previous methods, demonstrating the efficiency of our approach. Our
      approach will further facilitate the functional study of protein S-nitrosylation
      in cellular processes and may reveal new therapeutic targets.

PMID- 20687583
TI  - Binding kinetics of antiricin single domain antibodies and improved detection
      using a B chain specific binder.
AB  - Single domain antibodies are the recombinantly expressed binding fragments
      derived from heavy chain antibodies found in camels and llamas. These unique
      binding elements offer many desirable properties such as their small size (
      approximately 15 kDa) and thermal stability, which makes them attractive
      alternatives to conventional monoclonal antibodies. We created a phage display
      library from llamas immunized with ricin toxoid and selected a number of single
      domain antibodies. Phage selected on ricin were found to bind to either ricin A
      chain or the intact molecule; no ricin B chain binders were identified. By
      panning on B chain, we identified binders and have characterized their binding to
      the ricin B chain. While they have a poorer affinity than the previously
      described A chain binders, it was found that they performed dramatically better
      as capture reagents for the detection of ricin, providing a limit of detection in
      enzyme linked immunosorbent assay (ELISA) below 100 pg/mL and excellent
      specificity for ricin versus the highly related RCA 120 (1 to 10 000). We also
      reevaluated the previously isolated antiricin single domain antibody binding
      kinetics using surface plasmon resonance and found their K(d)s matched closely to
      those previously obtained under equilibrium binding conditions measured using the
      Luminex flow cytometer.

PMID- 20687584
TI  - Pulse-voltammetric glucose detection at gold junction electrodes.
AB  - A novel glucose sensing concept based on the localized change or "modulation" in
      pH within a symmetric gold-gold junction electrode is proposed. A paired gold
      gold junction electrode (average gap size ca. 500 nm) is prepared by simultaneous
      bipotentiostatic electrodeposition of gold onto two closely spaced platinum disk
      electrodes. For glucose detection in neutral aqueous solution, the potential of
      the "pH-modulator" electrode is set to -1.5 V vs saturated calomel reference
      electrode (SCE) to locally increase the pH, and simultaneously, either cyclic
      voltammetry or square wave voltammetry experiments are conducted at the sensor
      electrode. A considerable improvement in the sensor electrode response is
      observed when a normal pulse voltammetry sequence is applied to the modulator
      electrode (to generate "hydroxide pulses") and the glucose sensor electrode is
      operated with fixed bias at +0.5 V vs SCE (to eliminate capacitive charging
      currents). Preliminary data suggest good linearity for the glucose response in
      the medically relevant 1-10 mM concentration range (corresponding to 0.18-1.8 g
      L(-1)). Future electroanalytical applications of multidimensional pulse
      voltammetry in junction electrodes are discussed.

PMID- 20687586
TI  - Fabrication and chromatographic performance of porous-shell pillar-array columns.
AB  - We report on a new approach to obtain highly homogeneous silica-monolithic
      columns, applying a sol-gel fabrication process inside a rectangular pillar-array
      column (1 mm in width, 29 microm in height and 33.75 mm in length) having a cross
      sectional area comparable to that of a 200 microm diameter circular capillary.
      Starting from a silicon-based pillar array and working under high phase
      separation-tendency conditions (low poly(ethylene glycol) (PEG)-concentration),
      highly regular silica-based chromatographic systems with an external porosity in
      the order of 66-68% were obtained. The pillars, 2.4 microm in diameter, were
      typically clad with a 0.5 microm shell layer of silica, thus creating a 3.4
      microm total outer pillar diameter and leaving a minimal through-pore size of 2.2
      microm. After mesopore creation by hydrothermal treatment and column
      derivatization with octyldimethylchlorosilane, the monolithic column was used for
      chip-based liquid-chromatographic separations of coumarin dyes. Minimal plate
      heights ranging between 3.9 microm (nonretaining conditions) and 6 mum (for a
      retention factor of 6.5) were obtained, corresponding to domain-size-reduced
      plate heights ranging between 0.7 and 1.2. The column permeability was in the
      order of 1.3 x 10(13) m(2), lower than theoretically expected, but this is
      probably due to obstructions induced by the sol-gel process in the supply
      channels.

PMID- 20687585
TI  - Total synthesis of fostriecin: via a regio- and stereoselective polyene
      hydration, oxidation, and hydroboration sequence.
AB  - A total synthesis of the fostriecin has been achieved in 24 steps from enyne 11.
      The lactone moiety was installed by a Leighton allylation and Grubbs ring-closing
      metathesis reaction. The highly reactive Z,Z,E-triene moiety was installed via a
      late-stage Suzuki-Miyaura cross-coupling of a remarkably stable Z-vinyl boronate.
      The relative and absolute stereocenters of the C-8,9,11 triol were generated with
      a regio- and stereoselective asymmetric hydration/oxidation sequence.

PMID- 20687587
TI  - Reagentless measurement of aminoglycoside antibiotics in blood serum via an
      electrochemical, ribonucleic acid aptamer-based biosensor.
AB  - Biosensors built using ribonucleic acid (RNA) aptamers show promise as tools for
      point-of-care medical diagnostics, but they remain vulnerable to nuclease
      degradation when deployed in clinical samples. To explore methods for protecting
      RNA-based biosensors from such degradation we have constructed and characterized
      an electrochemical, aptamer-based sensor for the detection of aminoglycosidic
      antibiotics. We find that while this sensor achieves low micromolar detection
      limits and subminute equilibration times when challenged in buffer, it
      deteriorates rapidly when immersed directly in blood serum. In order to
      circumvent this problem, we have developed and tested sensors employing modified
      versions of the same aptamer. Our first effort to this end entailed the
      methylation of all of the 2'-hydroxyl groups outside of the aptamer's antibiotic
      binding pocket. However, while devices employing this modified aptamer are as
      sensitive as those employing an unmodified parent, the modification fails to
      confer greater stability when the sensor is challenged directly in blood serum.
      As a second potentially naive alternative, we replaced the RNA bases in the
      aptamer with their more degradation-resistant deoxyribonucleic acid (DNA)
      equivalents. Surprisingly and unlike control DNA-stem loops employing other
      sequences, this DNA aptamer retains the ability to bind aminoglycosides, albeit
      with poorer affinity than the parent RNA aptamer. Unfortunately, however, while
      sensors fabricated using this DNA aptamer are stable in blood serum, its lower
      affinity pushes their detection limits above the therapeutically relevant range.
      Finally, we find that ultrafiltration through a low-molecular-weight-cutoff spin
      column rapidly and efficiently removes the relevant nucleases from serum samples
      spiked with gentamicin, allowing the convenient detection of this aminoglycoside
      at clinically relevant concentrations using the original RNA-based sensor.

PMID- 20687588
TI  - Formation and growth of oxide layers at platinum and gold nano- and
      microelectrodes.
AB  - The construction and characterization of platinum and gold disk electrodes with
      minimum radii of 7 nm (platinum) and 500 nm (gold) is reported. The electrodes
      were prepared with a micropipet puller using a two step procedure and have been
      characterized using scanning electron microscopy, scanning electrochemical
      microscopy, high speed chronoamperometry, and cyclic voltammetry. The formation
      and growth of platinum and gold oxide layers, on the electrodes at time scales
      from microseconds to seconds, is reported. Significantly, the apparent
      microscopic area as determined by forming and subsequently reducing an oxide
      layer in acidic electrolyte using cyclic voltammetry depends dramatically on the
      scan rate. While conventional roughness factors between 1.8 and 3 are observed on
      average for scan rates above 5 V s(-1), the apparent roughness can exceed 30 for
      scan rates less than 0.5 V s(-1). Chronoamperometry, conducted on the microsecond
      to millisecond time scale, is used to probe the dynamics of monolayer and
      multilayer oxide formation as well as the reversibility of the oxide formation
      and removal. The latter study suggests that (at least for platinum) the growth of
      the oxide layer proceeds with a lower constant rate after an oxide monolayer is
      formed.

PMID- 20687590
TI  - A Pd6 molecular cage via multicomponent self-assembly incorporating both neutral
      and anionic linkers.
AB  - A Pd(6) molecular cage [{(tmen)Pd}(6)(bpy)(3)(tma)(2)](NO(3))(6) [1; where tmen =
      N,N,N',N'-tetramethylethylene diamine, bpy = 4,4'-bipyridyl, and H(3)tma =
      trimesic acid] was prepared via the template-free three-component self-assembly
      of a cis-blocked palladium(II) acceptor in combination with a tricarboxylate and
      a dipyridyl donor. Complex 1 represents the first example of a 3D palladium(II)
      cage of defined shape incorporating anionic and neutral linkers. Guest-induced
      exclusive formation of this cage was also monitored by an NMR study.

PMID- 20687589
TI  - Congruency between biophysical data from multiple platforms and molecular
      dynamics simulation of the double-super helix model of nascent high-density
      lipoprotein.
AB  - The predicted structure and molecular trajectories from >80 ns molecular dynamics
      simulation of the solvated Double-Super Helix (DSH) model of nascent high-density
      lipoprotein (HDL) were determined and compared with experimental data on
      reconstituted nascent HDL obtained from multiple biophysical platforms, including
      small angle neutron scattering (SANS) with contrast variation, hydrogen-deuterium
      exchange tandem mass spectrometry (H/D-MS/MS), nuclear magnetic resonance
      spectroscopy (NMR), cross-linking tandem mass spectrometry (MS/MS), fluorescence
      resonance energy transfer (FRET), electron spin resonance spectroscopy (ESR), and
      electron microscopy. In general, biophysical constraints experimentally derived
      from the multiple platforms agree with the same quantities evaluated using the
      simulation trajectory. Notably, key structural features postulated for the recent
      DSH model of nascent HDL are retained during the simulation, including (1) the
      superhelical conformation of the antiparallel apolipoprotein A1 (apoA1) chains,
      (2) the lipid micellar-pseudolamellar organization, and (3) the solvent-exposed
      Solar Flare loops, proposed sites of interaction with LCAT (lecithin cholesteryl
      acyltransferase). Analysis of salt bridge persistence during simulation provides
      insights into structural features of apoA1 that forms the backbone of the
      lipoprotein. The combination of molecular dynamics simulation and experimental
      data from a broad range of biophysical platforms serves as a powerful approach to
      studying large macromolecular assemblies such as lipoproteins. This application
      to nascent HDL validates the DSH model proposed earlier and suggests new
      structural details of nascent HDL.

PMID- 20687591
TI  - Comparative kinetics of cofactor association and dissociation for the human and
      trypanosomal S-adenosylhomocysteine hydrolases. 3. Role of lysyl and tyrosyl
      residues of the C-terminal extension.
AB  - On the basis of the available X-ray structures of S-adenosylhomocysteine
      hydrolases (SAHHs), free energy simulations employing the MM-GBSA approach were
      applied to predict residues important to the differential cofactor binding
      properties of human and trypanosomal SAHHs (Hs-SAHH and Tc-SAHH), within 5 A of
      the cofactor NAD(+)/NADH binding site. Among the 38 residues in this region, only
      four are different between the two enzymes. Surprisingly, the four nonidentical
      residues make no major contribution to differential cofactor binding between Hs
      SAHH and Tc-SAHH. On the other hand, four pairs of identical residues are shown
      by free energy simulations to differentiate cofactor binding between Hs-SAHH and
      Tc-SAHH. Experimental mutagenesis was performed to test these predictions for a
      lysine residue and a tyrosine residue of the C-terminal extension that penetrates
      a partner subunit to form part of the cofactor binding site. The K431A mutant of
      Tc-SAHH (TcK431A) loses its cofactor binding affinity but retains the wild type's
      tetrameric structure, while the corresponding mutant of Hs-SAHH (HsK426A) loses
      both cofactor affinity and tetrameric structure [Ault-Riche, D. B., et al. (1994)
      J. Biol. Chem. 269, 31472-31478]. The tyrosine mutants HsY430A and TcY435A alter
      the NAD(+) association and dissociation kinetics, with HsY430A increasing the
      cofactor equilibrium dissociation constant from approximately 10 nM (Hs-SAHH) to
      ~800 nM and TcY435A increasing the cofactor equilibrium dissociation constant
      from approximately 100 nM (Tc-SAHH) to ~1 mM. Both changes result from larger
      increases in the off rate combined with smaller decreases in the on rate. These
      investigations demonstrate that computational free energy decomposition may be
      used to guide experimental studies by suggesting sensitive sites for mutagenesis.
      Our finding that identical residues in two orthologous proteins may give
      significantly different binding free energy contributions strongly suggests that
      comparative studies of homologous proteins should investigate not only different
      residues but also identical residues in these proteins.

PMID- 20687592
TI  - Naphthalimide modified rhodamine derivative: ratiometric and selective
      fluorescent sensor for Cu2+ based on two different approaches.
AB  - A new rhodamine-based derivative bearing a 1,8-naphthalimide group (1) was
      synthesized as a dual-mode Cu(2+)-selective sensor via the rhodamine ring-opening
      approach and ratiometric displacement. A colorimetric and "off-on" signal for
      Cu(2+) through rhodamine ring opening in 1 and ratiometric fluorescent signal
      output when Cu(2+) displaces the bound Zn(2+) in the 1-Zn(2+) complex can be
      observed.

PMID- 20687593
TI  - A Pd-catalyzed approach to (1-->6)-linked C-glycosides.
AB  - A flexible and robust method for the assembly of (1-->6)-linked C-glycosidic
      disaccharides is presented. The key reaction is a Pd-catalyzed coupling of 1-iodo
      or 1-triflato-glycals with alkynyl glycosides. Reinstallation of the native
      hydroxyl group pattern is achieved after selective hydrogenation of the triple
      bond using Raney-nickel. Epoxidation with DMDO and reductive epoxide opening
      gives access to either the alpha- or the beta-derivative, depending on the
      hydride source.

PMID- 20687594
TI  - Pd-catalyzed assembly of spirooxindole natural products: a short synthesis of
      horsfiline.
AB  - The Pd-catalyzed intramolecular alpha-arylation of amides is applied to the
      synthesis of functionalized spirooxindoles. The substrate scope is evaluated, and
      the reaction is demonstrated to be useful for the assembly of spirooxindole
      natural products and derivatives thereof. As an application, a new synthesis of
      horsfiline 1 is presented, giving the natural product in only 4 steps from
      commercially available amino acid 12.

PMID- 20687595
TI  - Bacteria pattern spontaneously on periodic nanostructure arrays.
AB  - Surface-associated bacteria typically form self-organizing communities called
      biofilms. Spatial segregation is important for various bacterial processes
      associated with cellular and community development. Here, we demonstrate
      bacterial ordering and oriented attachment on the single-cell level induced by
      nanometer-scale periodic surface features. These surfaces cause spontaneous and
      distinct patterning phases, depending on their periodicity, which is observed for
      several strains, both gram positive and negative. This patterning is a general
      phenomenon that can control natural biofilm organization on the cellular level.

PMID- 20687596
TI  - Programmable soft lithography: solvent-assisted nanoscale embossing.
AB  - This paper reports an all-moldable nanofabrication platform that can generate,
      from a single master, large-area nanoscale patterns with programmable densities,
      fill factors, and lattice symmetries. Solvent-assisted nanoscale embossing (SANE)
      could increase the spacing of patterns up to 100% as well as decrease them down
      to 50% in a single step by stretching or heating a polymer substrate. Also, SANE
      could reduce critical feature sizes as small as 45% compared to the master by
      controlled swelling of patterned molds with different solvents. These
      capabilities were applied to generate plasmonic nanoparticle arrays with
      continuously variable separations and hence different optical properties on the
      same substrate.

PMID- 20687597
TI  - Multi-perspective analysis and spatiotemporal mapping of air pollution monitoring
      data.
AB  - Space-time data analysis and assimilation techniques in atmospheric sciences
      typically consider input from monitoring measurements. The input is often
      processed in a manner that acknowledges characteristics of the measurements
      (e.g., underlying patterns, fluctuation features) under conditions of
      uncertainty; it also leads to the derivation of secondary information that serves
      study-oriented goals, and provides input to space-time prediction techniques. We
      present a novel approach that blends a rigorous space-time prediction model
      (Bayesian maximum entropy, BME) with a cognitively informed visualization of high
      dimensional data (spatialization). The combined BME and spatialization approach
      (BME-S) is used to study monthly averaged NO2 and mean annual SO4 measurements in
      California over the 15-year period 1988-2002. Using the original scattered
      measurements of these two pollutants BME generates spatiotemporal predictions on
      a regular grid across the state. Subsequently, the prediction network undergoes
      the spatialization transformation into a lower-dimensional geometric
      representation, aimed at revealing patterns and relationships that exist within
      the input data. The proposed BME-S provides a powerful spatiotemporal framework
      to study a variety of air pollution data sources.

PMID- 20687598
TI  - OH reactivity measurements within a boreal forest: evidence for unknown reactive
      emissions.
AB  - Boreal forests emit large amounts of volatile organic compounds (VOCs) which
      react with the hydroxyl radical (OH) to influence regional ozone levels and form
      secondary organic aerosol. Using OH reactivity measurements within a boreal
      forest in Finland, we investigated the budget of reactive VOCs. OH reactivity was
      measured using the comparative reactivity method, whereas 30 individual VOCs were
      measured using proton transfer reaction mass spectrometry, thermal-desorption gas
      chromatography mass spectrometry, and liquid chromatography mass spectrometry, in
      August 2008. The measured OH reactivity ranged from below detection limit (3.5 s(
      1)), to approximately 60 s(-1) in a single pollution event. The average OH
      reactivity was approximately 9 s(-1) and no diel variation was observed in the
      profiles. The measured OH sinks (approximately 30 species) accounted for only 50%
      of the total measured OH reactivity, implying unknown reactive VOCs within the
      forest. The five highest measured OH sinks were: monoterpenes (1 s(-1)), CO (0.7
      s(-1)), isoprene (0.5 s(-1)), propanal and acetone (0.3 s(-1)), and methane (0.3
      s(-1)). We suggest that models be constrained by direct OH reactivity
      measurements to accurately assess the impact of boreal forest emissions on
      regional atmospheric chemistry and climate.

PMID- 20687599
TI  - Enhancement of anion recognition exhibited by a halogen-bonding rotaxane host
      system.
AB  - We report the first use of solution-phase halogen bonding to control and
      facilitate the assembly of an interlocked structure through the bromide anion
      templated formation of a rotaxane based upon an iodotriazolium axle. The
      incorporation of a halogen atom into the rotaxane host cavity dramatically
      improves the anion-recognition capabilities of the interlocked receptor, giving
      unusual iodide selectivity in a competitive aqueous medium.

PMID- 20687600
TI  - Decaplex and real-time PCR based detection of MON531 and MON15985 Bt cotton
      events.
AB  - The genetically modified (GM) Bt crops expressing delta-endotoxins from Bacillus
      thuringiensis provide protection against a wide range of lepidopteron insect
      pests throughout the growing season of the plant. Bt cotton is the only
      commercialized crop in India that is planted on an area of 7.6 million hectares.
      With the increase in development and commercialization of transgenic crops, it is
      necessary to develop appropriate qualitative and quantitative methods for
      detection of different transgenic events. The present study reports on the
      development of a decaplex polymerase chain reaction (PCR) assay for simultaneous
      detection of transgene sequences, specific transgene constructs, and endogenous
      stearoyl acyl desaturase (Sad1) gene in two events of Bt cotton, i.e., MON531 and
      MON15985. The decaplex PCR assay is an efficient tool to identify and
      discriminate the two major commercialized events of Bt cotton, i.e., MON531 and
      MON15985, in India. Real-time PCR assays were also developed for quantification
      of cry1Ac and cry2Ab genes being employed in these two events. The quantitative
      method was developed using seven serial dilutions containing different levels of
      Bt cotton DNA mixed with a non-Bt counterpart ranging from 0.01 to 100%. The
      results revealed that the biases from the true value and the relative standard
      deviations were all within the range of +/-20%. The limit of quantification (LOQ)
      of the developed real-time PCR method has also been established up to 0.01%.

PMID- 20687601
TI  - Gas-phase folding of a two-residue model peptide chain: on the importance of an
      interplay between experiment and theory.
AB  - In order to assess the ability of theory to describe properly the dispersive
      interactions that are ubiquitous in peptide and protein systems, an isolated
      short peptide chain has been studied using both gas-phase laser spectroscopy and
      quantum chemistry. The experimentally observed coexistence of an extended form
      and a folded form in the supersonic expansion was found to result from comparable
      Gibbs free energies for the two species under the high-temperature conditions (<
      or = 320 K) resulting from the laser desorption technique used to vaporize the
      molecules. These data have been compared to results obtained using a series of
      quantum chemistry methods, including DFT, DFT-D, and post-Hartree-Fock methods,
      which give rise to a wide range of relative stabilities predicted for these two
      forms. The experimental observation was best reproduced by an empirically
      dispersion-corrected functional (B97-D) and a hybrid functional with a
      significant Hartree-Fock exchange term (M06-2X). In contrast, the popular post
      Hartree-Fock method MP2, which is often used for benchmarking these systems, had
      to be discarded because of a very large basis-set superposition error. The
      applicability of the atomic counterpoise correction (ACP) is also discussed. This
      work also introduces the mandatory theoretical examination of experimental
      abundances. DeltaH(0 K) predictions are clearly not sufficient for discussion of
      folding, as the conformation inversion temperature is crucial to the conformation
      determination and requires taking into account thermodynamical corrections
      (DeltaG) in order to computationally isolate the most stable conformation.

PMID- 20687602
TI  - Aggregation and deposition of engineered nanomaterials in aquatic environments:
      role of physicochemical interactions.
AB  - The ever-increasing use of engineered nanomaterials will lead to heightened
      levels of these materials in the environment. The present review aims to provide
      a comprehensive overview of current knowledge regarding nanoparticle transport
      and aggregation in aquatic environments. Nanoparticle aggregation and deposition
      behavior will dictate particle transport potential and thus the environmental
      fate and potential ecotoxicological impacts of these materials. In this review,
      colloidal forces governing nanoparticle deposition and aggregation are outlined.
      Essential equations used to assess particle-particle and particle-surface
      interactions, along with Hamaker constants for specific nanoparticles and the
      attributes exclusive to nanoscale particle interactions, are described.
      Theoretical and experimental approaches for evaluating nanoparticle aggregation
      and deposition are presented, and the major findings of laboratory studies
      examining these processes are also summarized. Finally, we describe some of the
      challenges encountered when attempting to quantify the transport of nanoparticles
      in aquatic environments.

PMID- 20687603
TI  - Synthesis of 3-trifluoromethylbenzo[b]furans from phenols via direct ortho
      functionalization by extended Pummerer reaction.
AB  - A concise and diversity-oriented route to trifluoromethylbenzo[b]furans has been
      devised. A variety of phenols are directly converted to the corresponding 2
      methylthio-3-trifluoromethylbenzo[b]furans by new triflic-anhydride-mediated
      extended Pummerer annulation reactions with trifluoromethylketene dithioacetal
      monoxide. The methylthio group of the products undergoes further transformations,
      which increase the diversity of available trifluoromethylbenzo[b]furans.

PMID- 20687604
TI  - Catalytic enantioselective radical cyclization via regiodivergent epoxide
      opening.
AB  - A catalytic enantio- and diastereoselective radical cyclization using a
      regiodivergent epoxide opening (REO) for radical generation is described. It is
      demonstrated for the first time that the diastereoselectivity of cyclizations of
      acyclic radicals can be controlled catalytically. Building blocks for important
      applications in stereoselective synthesis are readily accessed.

PMID- 20687605
TI  - Preparation of translationally competent tRNA by direct chemical acylation.
AB  - Nonsense codon suppression for unnatural amino acid incorporation requires the
      preparation of a suppressor aminoacyl-tRNA. Chemical acylation strategies are
      general but inefficient and arduous. A recent report (J. Am. Chem. Soc. 2007,
      129, 15848) showed acylation of RNA mediated by lanthanum(III) using amino acid
      phosphate esters. The successful implementation of this methodology to full
      length suppressor tRNA is described, and it is shown that the derived aminoacyl
      tRNA is translationally competent in Xenopus oocytes.

PMID- 20687606
TI  - Self-doped Ti3+ enhanced photocatalyst for hydrogen production under visible
      light.
AB  - Through a facile one-step combustion method, partially reduced TiO(2) has been
      synthesized. Electron paramagnetic resonance (EPR) spectra confirm the presence
      of Ti(3+) in the bulk of an as-prepared sample. The UV-vis spectra show that the
      Ti(3+) here extends the photoresponse of TiO(2) from the UV to the visible light
      region, which leads to high visible-light photocatalytic activity for the
      generation of hydrogen gas from water. It is worth noting that the Ti(3+) sites
      in the sample are highly stable in air or water under irradiation and the
      photocatalyst can be repeatedly used without degradation in the activity.

PMID- 20687607
TI  - Silver-based nanodisk codes.
AB  - We report a novel method for synthesizing silver-based nanodisk code (NDC)
      structures using on-wire lithography, where we employ milder synthetic and
      etching conditions than those used to synthesize the analogous gold structures.
      The silver structures exhibit stronger surface-enhanced Raman scattering signals
      than their Au counterparts at 633 and 532 nm excitation and, therefore, lead to
      lower limits of detection when used in the context of DNA-based detection assays.
      Finally, use of two enhancing nanostructured materials in one disk code
      dramatically increases the information storage density for encoding. For example,
      a disk code consisting of 5 gold disk pairs has 13 unique combinations of
      enhancing patterns, while one with 5 disk pairs that can be either gold or silver
      has 98.

PMID- 20687608
TI  - Ganoderma lucidum polysaccharides attenuate endotoxin-induced intercellular cell
      adhesion molecule-1 expression in cultured smooth muscle cells and in the
      neointima in mice.
AB  - The expression of adhesion molecules on vessels and subsequent leukocyte
      recruitment are critical events in vascular diseases and inflammation. The aim of
      the present study was to examine the effects of an extract of Ganoderma lucidum
      (Reishi) polysaccharides (EORP), which is effective against cancer and
      immunological disorders, on adhesion molecule expression by human aortic smooth
      muscle cells (HASMCs) and the underlying mechanism. EORP significantly suppressed
      lipopolysaccharide (LPS)-induced intercellular cell adhesion molecule-1 (ICAM-1)
      mRNA and protein expression and reduced the binding of human monocytes to LPS
      stimulated HASMCs. Immunoprecipitation and real-time polymerase chain reaction
      demonstrated that EORP markedly reduced the interaction of human antigen R
      protein (HuR) with the 3'-UTR of ICAM-1 mRNA in LPS-stimulated HASMCs. EORP
      treatment also suppressed extracellular signal-regulated kinase (ERK)
      phosphorylation and reduced the density of the shifted bands of nuclear factor
      (NF)-kappaB after LPS-induced activation. In an endothelial-denuded artery model
      in LPS-treated mice, daily oral administration of EORP for 2 weeks decreased
      neointimal hyperplasia and ICAM-1 expression in the plasma and neointima. These
      results provide evidence that EORP attenuates LPS-induced adhesion molecule
      expression and monocyte adherence and that this protective effect is mediated by
      decreased ERK phosphorylation and NF-kappaB activation. These findings suggest
      that EORP has anti-inflammatory properties and could prove useful in the
      prevention of vascular diseases and inflammatory responses.

PMID- 20687609
TI  - Alpha,beta-unsaturated N-acylpyrrole peptidyl derivatives: new proteasome
      inhibitors.
AB  - Because of the encouraging results obtained using vinyl ester derivatives, we
      synthesized and tested a novel series of peptide-based proteasome inhibitors
      bearing a new pharmacophore unit at the C-terminal. N-Acylpyrrole moiety is a
      potential substrate for Michael addition by catalytic threonine. Several
      analogues have demonstrated a selective inhibition of the multicatalytic complex
      beta1 subunits, the capacity to permeate cellular membrane, and good
      pharmacokinetics properties.

PMID- 20687610
TI  - Development of potent glucagon-like peptide-1 agonists with high enzyme stability
      via introduction of multiple lactam bridges.
AB  - Glucagon-like peptide-1 (GLP-1) has the ability to lower the blood glucose level,
      and its regulatory functions make it an attractive therapeutic agent for the
      treatment of type 2 diabetes. However, its rapid degradation by enzymes like
      dipeptidyl peptidase-IV (DPP-IV) and neutral endopeptidase (NEP) 24.11 severely
      compromises its effective clinical use. Whereas specific DPP-IV inhibitors have
      been developed, NEP 24.11 targets multiple sites in the GLP-1 sequence, which
      makes it difficult to block. To address this drawback, we have designed and
      synthesized conformationally constrained GLP-1 analogues by introducing multiple
      lactam bridges that stabilized both alpha-helices in the N- and C-terminal
      regions simultaneously. In addition to improving the receptor activation
      capability (up to 5-fold) by fixing the alpha-helical conformations required for
      optimal receptor interaction, the introduced lactam bridges provided outstanding
      shielding over NEP 24.11 (half-life of >96 h). These highly constrained peptides
      are the first examples of NEP 24.11-resistant GLP-1 analogues.

PMID- 20687611
TI  - Identification of the position of mono-O-glucuronide of flavones and flavonols by
      analyzing shift in online UV spectrum (lambdamax) generated from an online diode
      array detector.
AB  - The beneficial pharmacological effects of flavonoids such as chemoprevention
      against cancer, aging, and heart diseases are severely limited due to their
      extensive in vivo glucuronidation by UDP-glucuronosyltransferases (UGTs). UGTs
      showed regiospecificity (i.e., position preference) in the glucuronidation of the
      flavonoids based on the substrate's chemical structure. In this paper,
      glucuronide(s) of 36 flavones and flavonols were generated using an in vitro
      glucuronidation reaction. UPLC/MS/MS was used to confirm the degree (mono- or di
      ) of glucuronidation in flavonoids with up to four hydroxyl groups. UV spectra of
      flavonoids and their respective mono-O-glucuronides were generated using UPLC
      with an online diode array detector. Analysis of the extent of shift in spectra
      of glucuronides in band I (300-385 nm) and band II (240-280 nm) regions as
      reflected by changes in lambdamax value was used to identify the position of
      glucuronidation. The data showed that glucuronidation of the 3- and 4'-hydroxyls
      resulted in band I lambdamax hypsochromic shifts (or blue shift) of 13-30 and 5
      10 nm, respectively. Glucuronidation of the 5-hydroxyl group caused a band II
      lambdamax hypsochromic shift of 5-10 nm. In contrast, glucuronidation of the 7
      hydroxyl group did not cause any lambdamax change in band I or II lambdamax,
      whereas glucuronidation of the 6-hydroxyl group did not cause predictable changes
      in lambdamax values. The paper demonstrated for the first time that a rapid and
      robust analysis method using lambdamax changes in online UV spectra can be used
      to pinpoint region-specific glucuronidation of flavones and flavonols with
      hydroxyl groups at the 4'-, 3-, 5-, and/or 7-position(s).

PMID- 20687612
TI  - Antioxidant activity of resveratrol in several fish lipid matrices: effect of
      acylation and glucosylation.
AB  - The antioxidant activity of resveratrol (1) and several acylated and glycosylated
      derivatives on fish oil enriched systems has been studied. Two long-chain
      acylated derivatives, 3-stearoylresveratrol (2) and 4'-stearoylresveratrol (3),
      and three glucosyl derivatives, resveratrol-3-beta-d-glucopyranoside (piceid, 4),
      resveratrol-3,5-di-beta-d-glucopyranoside (5), and resveratrol-3,4'-di-beta-d
      glucopyranoside (6), have been prepared and tested. The results have shown a
      notable antioxidant capacity of resveratrol and piceid in fish oil-in-water
      emulsions, similar to that of the potent antioxidant hydroxytyrosol.
      Lipophilization of resveratrol did not improve its antioxidant activity, either
      in emulsions or in bulk fish oil. Further glucosylation of piceid yielding
      compounds 5 and 6 did not improve either resveratrol or piceid antioxidant
      efficiency in emulsions or in bulk oil. In all of the examples, the hydroxyl
      group at the 4'-position seems to be relevant for the antioxidant efficiency of
      resveratrol, and it should be maintained to keep the antiradical activity.
      Finally, resveratrol has shown to be a very good antioxidant for fish muscle, as
      good as the potent antioxidant hydroxytyrosol.

PMID- 20687614
TI  - Profiling the outer membrane proteome during growth and development of the social
      bacterium Myxococcus xanthus by selective biotinylation and analyses of outer
      membrane vesicles.
AB  - Social behavior in the bacterium Myxococcus xanthus relies on contact-dependent
      activities involving cell-cell and cell-substratum interactions. To identify
      outer membrane proteins that have a role in these activities, we profiled the
      outer membrane proteome of growing and starving cells using two strategies.
      First, outer membrane proteins were enriched by biotinylation of intact cells
      using the reagent NHS (N-hydroxysuccinimide)-PEO(12) (polyethylene oxide)-biotin
      with subsequent membrane solubilization and affinity chromatography. Second, the
      proteome of outer membrane vesicles (OMV) was determined. Comparisons of detected
      proteins show that these methods have different detection profiles and together
      provide a comprehensive view of the outer membrane proteome. From 362 proteins
      identified, 274 (76%) were cell envelope proteins including 64 integral outer
      membrane proteins and 85 lipoproteins. The majority of these proteins were of
      unknown function. Among integral outer membrane proteins with homologues of known
      function, TonB-dependent transporters comprise the largest group. Our data
      suggest novel functions for these transporters. Among lipoproteins with
      homologues of known function, proteins with hydrolytic functions comprise the
      largest group. The luminal load of OMV was enriched for proteins with hydrolytic
      functions. Our data suggest that OMV have functions in predation and possibly in
      transfer of intercellular signaling molecules between cells.

PMID- 20687613
TI  - Single turnover kinetics of tryptophan hydroxylase: evidence for a new
      intermediate in the reaction of the aromatic amino acid hydroxylases.
AB  - Tryptophan hydroxylase (TrpH) uses a non-heme mononuclear iron center to catalyze
      the tetrahydropterin-dependent hydroxylation of tryptophan to 5
      hydroxytryptophan. The reactions of the TrpH.Fe(II), TrpH.Fe(II).tryptophan,
      TrpH.Fe(II).6MePH(4).tryptophan, and TrpH.Fe(II).6MePH(4).phenylalanine complexes
      with O(2) were monitored by stopped-flow absorbance spectroscopy and rapid quench
      methods. The second-order rate constant for the oxidation of TrpH.Fe(II) has a
      value of 104 M(-1) s(-1) irrespective of the presence of tryptophan. Stopped-flow
      absorbance analyses of the reaction of the TrpH.Fe(II).6MePH(4).tryptophan
      complex with oxygen are consistent with the initial step being reversible binding
      of oxygen, followed by the formation with a rate constant of 65 s(-1) of an
      intermediate I that has maximal absorbance at 420 nm. The rate constant for decay
      of I, 4.4 s(-1), matches that for formation of the 4a-hydroxypterin product
      monitored at 248 nm. Chemical-quench analyses show that 5-hydroxytryptophan forms
      with a rate constant of 1.3 s(-1) and that overall turnover is limited by a
      subsequent slow step, presumably product release, with a rate constant of 0.2 s(
      1). All of the data with tryptophan as substrate can be described by a five-step
      mechanism. In contrast, with phenylalanine as substrate, the reaction can be
      described by three steps: a second-order reaction with oxygen to form I, decay of
      I as tyrosine forms, and slow product release.

PMID- 20687615
TI  - Identification of novel proteins involved in plant cell-wall synthesis based on
      protein-protein interaction data.
AB  - The plant cell wall is mainly composed of polysaccharides, representing the
      richest source of biomass for future biofuel production. Currently, the majority
      of the cell-wall synthesis-related (CWSR) proteins are unknown even for model
      plant Arabidopsis thaliana. We report a computational framework for predicting
      CWSR proteins based on protein-protein interaction (PPI) data and known CWSR
      proteins. We predict a protein to be a CWSR protein if it interacts with known
      CWSR proteins (seeds) with high statistical significance. Using this technique,
      we predicted 100 candidate CWSR proteins in Arabidopsis thaliana, 8 of which were
      experimentally confirmed by previous reports. Forty-two candidates have either
      independent supporting evidence or strong functional relevance to cell-wall
      synthesis and, hence, are considered as the most reliable predictions. For 33 of
      the predicted CWSR proteins, we have predicted their detailed functional roles in
      CWS, based on analyses of their domain architectures, phylogeny, and current
      functional annotation in conjunction with a literature search. We present the
      constructed PPIs covering all the known and predicted CWSR proteins at
      http://csbl.bmb.uga.edu/~zhouchan/CellWallProtein/. The 42 most reliable
      candidates provide useful targets to experimentalists for further investigation,
      and the PPI data constructed in this work provides new information for cell-wall
      research.

PMID- 20687616
TI  - Drug or vaccine?: selecting the appropriate treatment for malignant glioma
      patients.
AB  - Malignant gliomas are the most common and aggressive form of brain tumour.
      Current combinations of aggressive surgical resection, radiation therapy and
      chemotherapy regimens do not significantly improve long-term patient survival for
      these cancers. Therefore, investigative therapies including tumour vaccines have
      targeted this devastating condition. This article reviews evidence and data on
      chemotherapy and immunotherapy for a personalized medicine approach in order to
      enable physicians to select the appropriate treatment for glioma patients.
      Dendritic cell- and peptide-based therapy for gliomas seems to be safe and
      without major adverse effects. Gene-modified vaccines have also shown promise in
      the treatment of malignant gliomas. The concept of 'personalized medicine' is
      currently important in oncology treatment development. Using a personalized
      medicine approach, it may be necessary to evaluate the molecular genetic
      abnormalities in individual patient tumours, and such findings should be the
      mainstay of immunotherapeutic strategies designed for the individual patient.

PMID- 20687617
TI  - Laxative abuse: epidemiology, diagnosis and management.
AB  - Laxatives have been used for health purposes for over 2000 years, and for much of
      that time abuse or misuse of laxatives has occurred. Individuals who abuse
      laxatives can generally be categorized as falling into one of four groups. By far
      the largest group is made up of individuals suffering from an eating disorder
      such as anorexia or bulimia nervosa. The prevalence of laxative abuse has been
      reported to range from approximately 10% to 60% of individuals in this group. The
      second group consists of individuals who are generally middle aged or older who
      begin using laxatives when constipated but continue to overuse them. This pattern
      may be promulgated on certain beliefs that daily bowel movements are necessary
      for good health. The third group includes individuals engaged in certain types of
      athletic training, including sports with set weight limits. The fourth group
      contains surreptitious laxative abusers who use the drugs to cause factitious
      diarrhoea and may have a factitious disorder. Normal bowel function consists of
      the absorption of nutrients, electrolytes and water from the gut. Most nutrients
      are absorbed in the small intestine, while the large bowel absorbs primarily
      water. There are several types of laxatives available, including stimulant
      agents, saline and osmotic products, bulking agents and surfactants. The most
      frequently abused group of laxatives are of the stimulant class. This may be
      related to the quick action of stimulants, particularly in individuals with
      eating disorders as they may erroneously believe that they can avoid the
      absorption of calories via the resulting diarrhoea. Medical problems associated
      with laxative abuse include electrolyte and acid/base changes that can involve
      the renal and cardiovascular systems and may become life threatening. The renin
      aldosterone system becomes activated due to the loss of fluid, which leads to
      oedema and acute weight gain when the laxative is discontinued. This can result
      in reinforcing further laxative abuse when a patient feels bloated and has gained
      weight. Treatment begins with a high level of suspicion, particularly when a
      patient presents with alternating diarrhoea and constipation as well as other
      gastrointestinal complaints. Checking serum electrolytes and the acid/base status
      can identify individuals who may need medical stabilization and confirm the
      severity of the abuse. The first step in treating laxative misuse once it is
      identified is to determine what may be promoting the behaviour, such as an eating
      disorder or use based on misinformation regarding what constitutes a healthy
      bowel habit. The first intervention would be to stop the stimulant laxatives and
      replace them with fibre/osmotic supplements utilized to establish normal bowel
      movements. Education and further treatment may be required to maintain a healthy
      bowel programme. In the case of an eating disorder, referral for psychiatric
      treatment is essential to lessen the reliance on laxatives as a method to alter
      weight and shape.

PMID- 20687618
TI  - Triptans for the management of migraine.
AB  - Migraine is a chronic, recurrent, disabling condition that affects millions of
      people in the US and worldwide. Proper acute care treatment for migraineurs is
      essential for a full return of function and productivity. Triptans are serotonin
      (5-HT)(1B/1D) receptor agonists that are generally effective, well tolerated and
      safe. Seven triptans are available worldwide, although not all are available in
      every country, with multiple routes of administration, giving doctors and
      patients a wide choice. Despite the similarities of the available triptans,
      pharmacological heterogeneity offers slightly different efficacy profiles. All
      triptans are superior to placebo in clinical trials, and some, such as
      rizatriptan 10 mg, eletriptan 40 mg, almotriptan 12.5 mg, and zolmitriptan 2.5
      and 5 mg are very similar to each other and to the prototype triptan, sumatriptan
      100 mg. These five are known as the fast-acting triptans. Increased dosing can
      offer increased efficacy but may confer a higher risk of adverse events, which
      are usually mild to moderate and transient in nature. This paper critically
      reviews efficacy, safety and tolerability for the different formulations of
      sumatriptan, zolmitriptan, rizatriptan, naratriptan, almotriptan, eletriptan and
      frovatriptan.

PMID- 20687619
TI  - Inactivated split-virion seasonal influenza vaccine (Fluarix): a review of its
      use in the prevention of seasonal influenza in adults and the elderly.
AB  - Fluarix is a trivalent, inactivated, split-virion influenza vaccine containing 15
      microg haemagglutinin from each of the three influenza virus strains (including
      an H1N1 influenza A virus subtype, an H3N2 influenza A virus subtype and an
      influenza B virus) that are expected to be circulating in the up-coming influenza
      season. Fluarix is highly immunogenic in healthy adults and elderly, and exceeds
      the criteria that make it acceptable for licensure in various regions (including
      the US and Europe). In a large, phase III, placebo-controlled, double-blind trial
      conducted in the US (2004/2005) in subjects aged 18-64 years, postvaccination
      seroconversion rates against the H1N1, H3N2 and B antigens were 60-78% and
      respective postvaccination seroprotection rates were 97-99% in Fluarix
      recipients. Another phase III trial conducted in the US (2005/2006) established
      the noninferiority of Fluarix versus another trivalent inactivated influenza
      virus vaccine in subjects aged >or=18 years, including a subgroup of elderly
      subjects. In annual European registration trials, Fluarix has consistently
      exceeded the immunogenicity criteria set by the EU Committee for Medicinal
      Products for Human Use for adults and the elderly. Fluarix demonstrated
      immunogenicity in small, open-label studies in at-risk subjects. During a year
      when the vaccine was well matched to the circulating strain, Fluarix demonstrated
      efficacy against culture-confirmed influenza A and/or B in a placebo-controlled
      trial in adults aged 18-64 years. In addition, Fluarix vaccination of pregnant
      women demonstrated efficacy in reducing the rate of laboratory-confirmed
      influenza in the infants and reducing febrile respiratory illnesses in the
      mothers and their new-born infants in a randomized trial. Fluarix was generally
      well tolerated in adults and the elderly in well designed clinical trials and in
      the annual European registration trials, with most local and general adverse
      events being transient and mild to moderate in intensity. The most common adverse
      reactions in recipients of Fluarix were pain, redness or swelling at the
      injection site, muscle aches, fatigue, headache and arthralgia. In conclusion,
      Fluarix is an important means of decreasing the impact of seasonal influenza
      viruses on adults and the elderly.

PMID- 20687621
TI  - Oral bepotastine: in allergic disorders.
AB  - Oral bepotastine is a second-generation histamine H(1) receptor antagonist that
      also suppresses some allergic inflammatory processes. Numerous short- and long
      term clinical trials and surveillance studies have shown that twice-daily
      bepotastine is an effective and generally well tolerated antihistamine in the
      treatment of patients with allergic rhinitis, chronic urticaria or pruritus
      associated with skin conditions (eczema/dermatitis, prurigo or pruritus
      cutaneus). Bepotastine 20 mg/day was significantly more effective than
      terfenadine 120 mg/day in patients with perennial allergic rhinitis, as evaluated
      by the final global improvement rating and several other endpoints in a phase III
      trial. In phase III trials in patients with chronic urticaria, bepotastine 20
      mg/day was more effective than placebo in improving levels of itching and
      eruption, and as effective as terfenadine 120 mg/day with regard to the final
      global improvement rating and other endpoints. In a noncomparative trial in
      patients with pruritus associated with skin diseases, the majority of bepotastine
      recipients in the overall population, as well as in the specific skin disease
      subgroups (eczema/dermatitis, prurigo or pruritus cutaneus), had a final global
      improvement rating of moderate or greater. Bepotastine was generally well
      tolerated in adult and paediatric patients with allergic conditions.

PMID- 20687620
TI  - Glatiramer acetate: a review of its use in relapsing-remitting multiple sclerosis
      and in delaying the onset of clinically definite multiple sclerosis.
AB  - Glatiramer acetate is a synthetic analogue of the multiple sclerosis (MS)
      associated antigen, myelin basic protein. It is indicated in the EU, US and many
      other countries to reduce the frequency of relapses in patients with relapsing
      remitting MS (RRMS), and for the treatment of patients who have experienced a
      well defined first clinical episode and are at high risk of developing clinically
      definite MS or have features of MS on MRI. The efficacy of glatiramer acetate in
      patients with RRMS has been shown in two randomized, double-blind, multicentre
      phase III trials. In one trial, glatiramer acetate was associated with a
      significantly lower mean relapse rate than placebo after 24 months' treatment
      (primary endpoint). In an ongoing open-label extension to this trial, glatiramer
      acetate was associated with a sustained reduction in the relapse rate at the 6-,
      8- and 15-year follow-ups. In the other trial, the mean cumulative number of
      gadolinium-enhancing lesions on T1-weighted MRI images was significantly lower in
      glatiramer acetate versus placebo recipients after 9 months' treatment (primary
      endpoint). Glatiramer acetate also had generally similar efficacy to subcutaneous
      interferon (IFN)-beta-1a or IFNbeta-1b in two large randomized, open-label,
      multicentre phase III trials conducted over 96 weeks or >or=2 years. These data
      were supported by those from a smaller randomized, open-label phase IV trial that
      utilized a unique imaging protocol to evaluate the efficacy of glatiramer acetate
      versus that of IFNbeta-1b over >or=2 years. In these trials, there was no
      significant difference between glatiramer acetate and IFNbeta recipients in any
      of the clinical endpoints at study end (e.g. time to first relapse [primary
      endpoint of the REGARD trial] or risk of relapse [primary endpoint of the BEYOND
      trial]). Moreover, there was no significant difference between glatiramer acetate
      and IFNbeta-1b recipients in the median number of combined active lesions per
      patient per monthly MRI scan during the first 12 months of treatment (primary
      endpoint of the BECOME trial). In general, there was no significant between-group
      difference in the majority of other MRI-assessed endpoints in any of the trials.
      The efficacy of glatiramer acetate in patients with clinically isolated syndrome
      (CIS) was established in a randomized, double-blind, double-dummy, multicentre
      phase III trial (the PreCISe trial). In this study, glatiramer acetate was
      associated with a significantly longer time to conversion to clinically definite
      MS than placebo (primary endpoint). Glatiramer acetate was generally well
      tolerated in clinical trials, with most adverse events being mild to moderate in
      severity. Injection site-related reactions and immediate post-injection systemic
      reactions were the most frequently observed adverse events associated with
      glatiramer acetate in clinical studies. In conclusion, glatiramer acetate is a
      valuable first-line option in the treatment of RRMS, as well as being an option
      in the treatment of CIS.

PMID- 20687622
TI  - Dexlansoprazole modified release: in erosive oesophagitis and non-erosive reflux
      disease.
AB  - Dexlansoprazole modified release (dexlansoprazole MR) is an orally administered
      delayed-release formulation of the R-enantiomer of the proton pump inhibitor
      lansoprazole that is effective in improving the healing of all grades of erosive
      oesophagitis, maintaining the healing of erosive oesophagitis and in the
      treatment of symptomatic non-erosive reflux disease (NERD). In two large,
      identical, 8-week, randomized, double-blind, multicentre phase III trials,
      dexlansoprazole MR 60 mg once daily achieved complete healing in >or=92% of
      patients with all grades of erosive oesophagitis (primary endpoint) and was
      noninferior to lansoprazole 30 mg once daily using life-table analysis. Moreover,
      in a randomized, double-blind, multicentre phase III trial in patients with
      healed erosive oesophagitis, dexlansoprazole MR 30 mg once daily was
      significantly more effective than placebo in maintaining healing following 6
      months' treatment (primary endpoint). In addition, the proportion of 24-hour
      heartburn-free days (primary endpoint) was significantly greater in recipients of
      dexlansoprazole MR 30 mg once daily than in recipients of placebo following 4
      weeks' treatment in a large, randomized, double-blind, multicentre phase III
      trial in patients with NERD. Dexlansoprazole MR 30 or 60 mg once daily was
      generally well tolerated in a pooled analysis of clinical trials of up to 12
      months' duration.

PMID- 20687623
TI  - Oral colchicine (Colcrys): in the treatment and prophylaxis of gout.
AB  - Oral colchicine (Colcrys) is approved in the US for the treatment of acute gout
      flares in adult patients and the prophylaxis of gout flares in patients aged >16
      years. Colchicine is a tricyclic alkaloid that interrupts multiple inflammatory
      response pathways. Its principal mechanism of action in gout is thought to be
      inhibition of cytoskeletal microtubule polymerization, an important process in
      neutrophil functioning. In a phase III, randomized, double-blind, placebo
      controlled, multicentre trial, the recommended dosage of Colcrys (1.2 mg at the
      first sign of the flare, followed by 0.6 mg in 1 hour) was significantly more
      effective than placebo in treating acute gout flare, as assessed by the
      proportion of patients experiencing a >or=50% reduction in pain within 24 hours
      of initiating treatment. In a randomized, double-blind, placebo-controlled,
      single-centre trial, non-approved colchicine 0.6 mg once or twice daily (up to 6
      months) was more effective than placebo in preventing gout flares in patients
      receiving allopurinol as urate-lowering therapy. At the recommended dosage for
      the treatment of acute gout flares, Colcrys was as well tolerated as placebo in
      patients with gout. The incidence of the most common adverse events was similar
      between recipients of the recommended dosage of Colcrys and placebo.

PMID- 20687625
TI  - Communication: High-frequency acoustic excitations and boson peak in glasses: A
      study of their temperature dependence.
AB  - The results of a combined experimental study of the high-frequency acoustic
      dynamics and of the vibrational density of states (VDOS) as a function of
      temperature in a glass of sorbitol are reported here. The excess in the VDOS at
      approximately 4.5 meV over the Debye, elastic continuum prediction (boson peak)
      is found to be clearly related to anomalies observed in the acoustic dispersion
      curve in the mesoscopic wavenumber range of few nm(-1). The quasiharmonic
      temperature dependence of the acoustic dispersion curves offers a natural
      explanation for the observed scaling of the boson peak with the elastic medium
      properties.

PMID- 20687624
TI  - Roflumilast: in chronic obstructive pulmonary disease.
AB  - Roflumilast is an orally administered, selective phosphodiesterase 4 inhibitor
      that is a novel treatment for patients with severe chronic obstructive pulmonary
      disease (COPD). Across four randomized, double-blind, multinational trials in
      patients with moderate to severe or severe COPD, roflumilast 500 microg/day
      produced significantly greater improvements from baseline than placebo in pre-
      and post-bronchodilator forced expiratory volume in 1 second (FEV(1)). While mean
      increases in FEV(1) in roflumilast groups were small, they were in marked
      contrast to the decreases or negligible increase in FEV(1) in the placebo groups.
      In three of four trials, roflumilast significantly reduced the COPD exacerbation
      rate; in a pooled analysis of two 52-week trials, roflumilast was associated with
      a 17% reduction over placebo. Further randomized, double-blind, multinational
      trials compared roflumilast 500 microg plus salmeterol with placebo plus
      salmeterol and roflumilast 500 microg plus tiotropium bromide with placebo plus
      tiotropium bromide. In both trials, roflumilast plus long-acting bronchodilator
      produced significantly greater increases in pre- and post-bronchodilator FEV(1)
      than placebo plus long-acting bronchodilator. Roflumilast had an acceptable
      tolerability profile. In a pooled analysis of two trials, 19% and 22% of
      roflumilast and placebo recipients had serious adverse events; in the
      corresponding groups, 14% and 11% discontinued medications because of adverse
      events.

PMID- 20687626
TI  - Communication: Electric properties of the ThO(X (1)Sigma(+)) molecule.
AB  - To assist the proposed search for the electric dipole moment of the electron with
      the thorium oxide, converged ab initio coupled cluster calculations are performed
      on the interaction energy, dipole moment, anisotropic static dipole
      polarizability, and quadrupole moment of the ThO(X (1)Sigma(+)) molecule as
      functions of internuclear distance. The rovibrational energy levels and wave
      functions are computed to derive the spectroscopic constants and matrix elements
      of electric properties. Ab initio calculations provide good agreement with the
      measured spectroscopic constants but call for a revision of the dissociation
      energy estimates from mass-spectrometric measurements and previous calculations.

PMID- 20687627
TI  - Insights into the orbital invariance problem in state-specific multireference
      coupled cluster theory.
AB  - In this communication we report the results of our studies on the orbital
      invariance properties of the state-specific multireference coupled cluster
      approach suggested by Mukherjee and co-workers (Mk-MRCC). In particular, we have
      gathered numerical evidence to show that even when the linear excitation manifold
      is modified in order to span the same space for each reference, the resulting
      method is not orbital invariant. In order to test this conjecture we have
      proposed a new truncation scheme (Mk-MRCCSDtq) which, in addition to full single
      and double excitations, contains partial triple and quadruple excitations. For a
      reference space generated by all possible combinations of two electrons in two
      orbitals, the linear excitation manifold of Mk-MRCCSDtq spans the same set for
      each reference determinant. Mk-MRCCSDtq is found to lack energy invariance for
      rotations among active molecular orbitals but it is less sensitive to orbital
      rotations than the conventional scheme which includes only singles and doubles
      (Mk-MRCCSD). Nevertheless, Mk-MRCCSDtq is a very accurate method, superior with
      respect to multireference configuration interaction approaches, and competitive
      with the active-space coupled cluster method and the MRexpT ansatz.

PMID- 20687628
TI  - An efficient density-functional-theory force evaluation for large molecular
      systems.
AB  - An efficient, linear-scaling implementation of Kohn-Sham density-functional
      theory for the calculation of molecular forces for systems containing hundreds of
      atoms is presented. The density-fitted Coulomb force contribution is calculated
      in linear time by combining atomic integral screening with the continuous fast
      multipole method. For higher efficiency and greater simplicity, the near-field
      Coulomb force contribution is calculated by expanding the solid-harmonic Gaussian
      basis functions in Hermite rather than Cartesian Gaussians. The efficiency and
      linear complexity of the molecular-force evaluation is demonstrated by sample
      calculations and applied to the geometry optimization of a few selected large
      systems.

PMID- 20687629
TI  - Ab initio statistical mechanics of surface adsorption and desorption. II. Nuclear
      quantum effects.
AB  - We show how the path-integral formulation of quantum statistical mechanics can be
      used to construct practical ab initio techniques for computing the chemical
      potential of molecules adsorbed on surfaces, with full inclusion of quantum
      nuclear effects. The techniques we describe are based on the computation of the
      potential of mean force on a chosen molecule and generalize the techniques
      developed recently for classical nuclei. We present practical calculations based
      on density functional theory with a generalized-gradient exchange-correlation
      functional for the case of H(2)O on the MgO (001) surface at low coverage. We
      note that the very high vibrational frequencies of the H(2)O molecule would
      normally require very large numbers of time slices (beads) in path-integral
      calculations, but we show that this requirement can be dramatically reduced by
      employing the idea of thermodynamic integration with respect to the number of
      beads. The validity and correctness of our path-integral calculations on the
      H(2)O/MgO(001) system are demonstrated by supporting calculations on a set of
      simple model systems for which quantum contributions to the free energy are known
      exactly from analytic arguments.

PMID- 20687630
TI  - Accurate calculations of the hydration free energies of druglike molecules using
      the reference interaction site model.
AB  - We report on the results of testing the reference interaction site model (RISM)
      for the estimation of the hydration free energy of druglike molecules. The
      optimum model was selected after testing of different RISM free energy
      expressions combined with different quantum mechanics and empirical force-field
      methods of structure optimization and atomic partial charge calculation. The
      final model gave a systematic error with a standard deviation of 2.6 kcal/mol for
      a test set of 31 molecules selected from the SAMPL1 blind challenge set [J. P.
      Guthrie, J. Phys. Chem. B 113, 4501 (2009)]. After parametrization of this model
      to include terms for the excluded volume and the number of atoms of different
      types in the molecule, the root mean squared error for a test set of 19 molecules
      was less than 1.2 kcal/mol.

PMID- 20687631
TI  - A multistage ab initio quantum wavepacket dynamics formalism for electronic
      structure and dynamics in open systems.
AB  - We propose a multistage quantum wavepacket dynamical treatment for the study of
      delocalized electronic systems as well as electron transport through donor-bridge
      acceptor systems such as those found in molecular-wire/electrode networks. The
      full donor-bridge-acceptor system is treated through a rigorous partitioning
      scheme that utilizes judiciously placed offsetting absorbing and emitting
      boundary conditions. These facilitate a computationally efficient and potentially
      accurate treatment of the long-range coupling interactions between the bridge and
      donor/acceptor systems and the associated open system boundary conditions. Time
      independent forms of the associated, partitioned equations are also derived. In
      the time-independent form corresponding to the bridge system, coupling to donor
      and acceptor, that is long-range interactions, is completely accounted. For the
      time-dependent study, the quantum dynamics of the electronic flux through the
      bridge-donor/acceptor interface is constructed using an accurate and efficient
      representation of the discretized quantum-mechanical free-propagator. A model for
      an electrode-molecular wire-electrode system is used to test the accuracy of the
      scheme proposed. Transmission probability is obtained directly from the
      probability density of the electronic flux in the acceptor region. Conductivity
      through the molecular wire is computed using a wavepacket flux correlation
      function.

PMID- 20687632
TI  - Determination of spin Hamiltonians from projected single reference configuration
      interaction calculations. I. Spin 1/2 systems.
AB  - The most reliable wave-function based treatments of magnetic systems usually
      start from a complete active space self-consistent field calculation of the
      magnetic electrons in the magnetic orbitals, followed by extensive and expensive
      configuration interaction (CI) calculations. This second step, which introduces
      crucial spin polarization and dynamic correlation effects, is necessary to reach
      reliable values of the magnetic coupling constants. The computational cost of
      these approaches increases exponentially with the number of unpaired electrons.
      The single-determinantal unrestricted density functional Kohn-Sham calculations
      are computationally much simpler, and may provide reasonable estimates of these
      quantities, but their results are strongly dependent on the chosen exchange
      correlation potential. The present work, which may be seen as an ab initio
      transcription of the unrestricted density functional theory technique, returns to
      the perturbative definition of the Heisenberg Hamiltonian as an effective
      Hamiltonian, and proposes a direct estimate of its diagonal energies through
      single reference CI calculations. The differences between these diagonal terms
      actually determine the entire Heisenberg Hamiltonian. The reference determinants
      must be vectors of the model space and the components on the other vectors of the
      model space are cancelled along the iterative process. The method is successfully
      tested on a series of bicentric and multicentric spin 12 systems. The projected
      single reference difference dedicated CI treatment is both accurate and of
      moderate cost. It opens the way to parameter-free calculations of large spin
      assemblies.

PMID- 20687633
TI  - Embedding theory for excited states.
AB  - Using the technique of Perdew and Levy [Phys. Rev. B 31, 6264 (1985)], it is
      shown that both the density function theory (DFT)-in-DFT and wave function theory
      (WFT)-in-DFT embedding approaches are formally correct in studying not only the
      ground state but also a subset of the excited states of the total system. Without
      further approximations, the DFT-in-DFT embedding approach results in a pair of
      coupled Euler-Lagrange equations. In contrast to DFT-in-DFT, the WFT-in-DFT
      approach is shown to ensure a systematic description of excited states if such
      states are mainly related to excitations within the embedded subsystem. Possible
      ways for the practical realization of the WFT-in-DFT approach for studying
      excited states are briefly discussed.

PMID- 20687634
TI  - A computational study of ultrafast acid dissociation and acid-base neutralization
      reactions. I. The model.
AB  - Ultrafast, time-resolved investigations of acid-base neutralization reactions
      have recently been performed using systems containing the photoacid 8
      hydroxypyrene-1,3,6-trisulfonic acid trisodium salt (HPTS) and various Bronsted
      bases. Two conflicting neutralization mechanisms have been formulated by Mohammed
      et al. [Science 310, 83 (2005)] and Siwick et al. [J. Am. Chem. Soc. 129, 13412
      (2007)] for the same acid-base system. Herein an ab initio molecular dynamics
      based computational model is formulated, which is able to investigate the
      validity of the proposed mechanisms in the general context of ground-state acid
      base neutralization reactions. Our approach consists of using 2,4,6
      tricyanophenol (exp. pKa congruent with 1) as a model for excited-state HPTS( *)
      (pKa congruent with 1.4) and carboxylate ions for the accepting base. We employ
      our recently proposed dipole-field/quantum mechanics (QM) treatment [P. Maurer
      and R. Iftimie, J. Chem. Phys. 132, 074112 (2010)] of the proton donor and
      acceptor molecules. This approach allows one to tune the free energy of
      neutralization to any desired value as well as model initial nonequilibrium
      hydration effects caused by a sudden increase in acidity, making it possible to
      achieve a more realistic comparison with experimental data than could be obtained
      via a full-QM treatment of the entire system. It is demonstrated that the dipole
      field/QM model reproduces correctly key properties of the 2,4,6-tricyanophenol
      acid molecule including gas-phase proton dissociation energies and dipole
      moments, and condensed-phase hydration structure and pKa values.

PMID- 20687635
TI  - Analyzing molecular static linear response properties with perturbed localized
      orbitals.
AB  - Perturbed localized molecular orbitals (LMOs), correct to first order in an
      applied static perturbation and consistent with a chosen localization functional,
      are calculated using analytic derivative techniques. The formalism is outlined
      for a general static perturbation and variational localization functionals.
      Iterative and (formally) single-step approaches are compared. The implementation
      employs an iterative sequence of 2x2 orbital rotations. The procedure is verified
      by calculations of molecular electric-field perturbations. Boys LMO contributions
      to the electronic static polarizability and the electric-field perturbation of
      the r(2) expectation value are calculated and analyzed for ethene, ethyne, and
      fluoroethene (H(2)C=CHF). For ethene, a comparison is made with results from a
      Pipek-Mezey localization. The calculations show that a chemically intuitive
      decomposition of the calculated properties is possible with the help of the LMO
      contributions and that the polarizability contributions in similar molecules are
      approximately transferable.

PMID- 20687636
TI  - Solid-liquid surface free energy of Lennard-Jones liquid on smooth and rough
      surfaces computed by molecular dynamics using the phantom-wall method.
AB  - Different model Lennard-Jones solid-liquid interfaces have been considered. In
      the systems, either the interaction strength between solid and liquid was varied,
      or the topography of the solid surface was modified. In all situations, the solid
      liquid interfacial free energy variations with respect to a reference solid
      liquid interface were quantified by means of a thermodynamic integration method
      [F. Leroy et al., Macromol. Rapid Commun. 30, 864 (2009)], referred to as the
      phantom-wall method. Additionally, the liquid-vapor surface free energy was
      determined. This result was combined with Young's equation for contact angle
      calculations of cylindrical liquid droplets. It allowed us to show that the
      change in contact angle of a droplet placed on smooth solid surfaces with respect
      to solid-liquid interaction strength could be obtained by neglecting the solid
      vapor surface free energy contribution when the solid-liquid interaction was
      weak. We also showed that the implementation of roughness by means of parallel
      grooves whose the density was varied could yield either higher or lower solid
      liquid surface free energy, depending on the solid-liquid surface free energy of
      the smooth interface. Roughness led to lower surface free energy when the smooth
      surface had favorable interaction with the liquid, while it led to a higher
      surface free energy when the smooth surface had loose interactions with the
      liquid, though the effect was found to be weak. The consistency of the whole set
      of results, as well as agreement with the existing results on similar systems,
      shows the ability of the thermodynamic integration method employed here to
      capture the variation of interfacial thermodynamic quantities when modifying
      either the chemical nature or the topography of a solid surface in contact with a
      given liquid phase.

PMID- 20687637
TI  - Multi-Jastrow trial wavefunctions for electronic structure calculations with
      quantum Monte Carlo.
AB  - A new type of electronic trial wavefunction suitable for quantum Monte Carlo
      calculations of molecular systems is presented. In contrast with the standard
      Jastrow-Slater form built with a unique global Jastrow term, it is proposed to
      introduce individual Jastrow factors attached to molecular orbitals. Such a form
      is expected to be more physical since it allows to describe differently the local
      electronic correlations associated with various molecular environments (1s-core
      orbitals, 3d-magnetic orbitals, localized two-center sigma-orbitals, delocalized
      pi-orbitals, atomic lone pairs, etc.). In contrast with the standard form,
      introducing different Jastrow terms allows us to change the nodal structure of
      the wavefunction, a point which is important in the context of building better
      nodes for more accurate fixed-node diffusion Monte Carlo (FN-DMC) calculations.
      Another important aspect resulting from the use of local Jastrow terms is the
      possibility of defining and preoptimizing local and transferable correlated units
      for building complex trial wavefunctions from simple parts. The practical aspects
      associated with the computation of the intricate derivatives of the multi-Jastrow
      trial function are presented in detail. Some first illustrative applications for
      atoms of increasing size (O, S, and Cu) and for the potential energy curve and
      spectroscopic constants of the FH molecule are presented. In the case of the
      copper atom, the use of the multi-Jastrow form at the variational Monte Carlo
      level has allowed us to improve significantly the value of the total ground-state
      energy (about 75% of the correlation energy with only one determinant and three
      atomic orbital Jastrow factors). In the case of the FH molecule (fluorine
      hydride), it has been found that the multi-Jastrow nodes lead to an almost exact
      FN-DMC value of the dissociation energy [D(0)=-140.7(4) kcal/mol instead of the
      estimated nonrelativistic Born-Oppenheimer exact value of -141.1], which is not
      the case with standard nodes, D(0)=-138.3(4) kcal/mol.

PMID- 20687638
TI  - Fluctuating dynamics of nematic liquid crystals using the stochastic method of
      lines.
AB  - We construct Langevin equations describing the fluctuations of the tensor order
      parameter Q(alphabeta) in nematic liquid crystals by adding noise terms to time
      dependent variational equations that follow from the Ginzburg-Landau-de Gennes
      free energy. The noise is required to preserve the symmetry and tracelessness of
      the tensor order parameter and must satisfy a fluctuation-dissipation relation at
      thermal equilibrium. We construct a noise with these properties in a basis of
      symmetric traceless matrices and show that the Langevin equations can be solved
      numerically in this basis using a stochastic version of the method of lines. The
      numerical method is validated by comparing equilibrium probability distributions,
      structure factors, and dynamic correlations obtained from these numerical
      solutions with analytic predictions. We demonstrate excellent agreement between
      numerics and theory. This methodology can be applied to the study of phenomena
      where fluctuations in both the magnitude and direction of nematic order are
      important, as for instance, in the nematic swarms which produce enhanced
      opalescence near the isotropic-nematic transition or the problem of nucleation of
      the nematic from the isotropic phase.

PMID- 20687639
TI  - Electronic excitation energy calculation by the fragment molecular orbital method
      with three-body effects.
AB  - A scheme for full quantum electronic excited state calculation is proposed that
      is based on the fragment molecular orbital (FMO) method with three-body effects.
      The accuracy and efficiency of this scheme is checked by calculating the
      excitation energy of hydrated formaldehyde and hydrated phenol. In all cases,
      three-body effects improved the excitation energy by the one- and two-body FMO
      methods with small computational cost, and the excitation energy approached more
      closely the full calculation value. The results also show that the three-body
      effects were relatively large and cannot be neglected.

PMID- 20687640
TI  - Free energy calculation using molecular dynamics simulation combined with the
      three dimensional reference interaction site model theory. I. Free energy
      perturbation and thermodynamic integration along a coupling parameter.
AB  - This article proposes a free energy calculation method based on the molecular
      dynamics simulation combined with the three dimensional reference interaction
      site model theory. This study employs the free energy perturbation (FEP) and the
      thermodynamic integration (TDI) along the coupling parameters to control the
      interaction potential. To illustrate the method, we applied it to a complex
      formation process in aqueous solutions between a crown ether molecule 18-Crown-6
      (18C6) and a potassium ion as one of the simplest model systems. Two coupling
      parameters were introduced to switch the Lennard-Jones potential and the Coulomb
      potential separately. We tested two coupling procedures: one is a "sequential
      coupling" to couple the Lennard-Jones interaction followed by the Coulomb
      coupling, and the other is a "mixed-coupling" to couple both the Lennard-Jones
      and the Coulomb interactions together as much as possible. The sequential
      coupling both for FEP and TDI turned out to be accurate and easily handled since
      it was numerically well-behaved. Furthermore, it was found that the sequential
      coupling had relatively small statistical errors. TDI along the mixed-coupling
      integral path was to be carried out carefully, paying attention to a numerical
      behavior of the integrand. The present model system exhibited a nonmonotonic
      behavior in the integrands for TDI along the mixed-coupling integral path and
      also showed a relatively large statistical error. A coincidence within a
      statistical error was obtained among the results of the free energy differences
      evaluated by FEP, TDI with the sequential-coupling, and TDI with the mixed
      coupling. The last one is most attractive in terms of the computer power and is
      accurate enough if one uses a proper set of windows, taking the numerical
      behavior of the integrands into account. TDI along the sequential-coupling
      integral path would be the most convenient among the methods we tested, since it
      seemed to be well-balanced between the computational load and the accuracy. The
      numerical results reported in this article qualitatively agree with the
      experimental data for the potassium ion recognition by the 18C6 in aqueous
      solution.

PMID- 20687641
TI  - An efficient umbrella potential for the accurate calculation of free energies by
      molecular simulation.
AB  - Umbrella sampling has been widely used to calculate free energies in many
      chemical and biological applications because it can effectively bridge the
      systems of interest and sample in the united phase space that is essential to
      yield accurate results. Many algorithms have implemented the idea of umbrella
      sampling that greatly improves the calculation of free energies. An efficient
      umbrella potential not only can connect the systems of interest, but also can
      lower the energetic barriers and facilitate the sampling over the relevant phase
      spaces. Here we present such an umbrella potential that is built on the equations
      of the weighted histogram analysis method. The proposed umbrella potential can
      facilitate the sampling of the important phase spaces of the systems of interest,
      which ensures the accurate calculation of free energies. We test this umbrella
      potential using a harmonic-model system, a water system, and a Lennard-Jones
      system. We demonstrate that this umbrella potential is effective in the
      circumstances when the systems of interest do not exhibit overlap in their phase
      spaces.

PMID- 20687642
TI  - Hartree-Fock perturbative corrections for total and reaction energies.
AB  - We have performed an assessment of the Hartree-Fock perturbative correction
      (HFPC) on a large and diverse set of molecules and reactions. Errors in both
      absolute and reaction energies with respect to converged secondary basis Hartree
      Fock results are reported for a wide spectrum of primary/secondary basis set
      combinations. These results show that using an adequate primary basis, HFPC can
      accurately reproduce secondary basis energies at a substantially reduced cost.
      Comparisons of HFPC with the related dual basis Hartree-Fock (DBHF) scheme are
      also made for several molecules and target secondary basis sets. Our results
      indicate that HFPC is faster and more accurate than DBHF for approaching triple
      zeta basis sets. For quadruple-zeta secondary basis sets, HFPC is capable of
      yielding more accurate energies at a marginally increased cost over DBHF.

PMID- 20687643
TI  - Transferability of anharmonic force fields in simulations of molecular
      vibrations.
AB  - Accurate simulations of vibrational molecular spectra require precise molecular
      force fields, at least with cubic and quartic anharmonic corrections beyond the
      harmonic limits. Generation of such force field terms becomes computationally
      prohibitive for larger molecules. In this work, an alternate possibility is
      explored, where approximate anharmonic force field components are obtained from
      molecular fragments. Transferability properties of the cubic and incomplete
      quartic fields are discussed and tested on model oligoproline molecules.
      Automatic transfer schemes including cubic, two and three atomic quartic force
      constants are developed and implemented. The results indicate that the main
      vibrational interactions in molecules are local and the anharmonic constants are
      mostly well amendable to the transfer. Exact anharmonic normal mode force fields
      of larger molecules compared very well to those obtained from smaller molecular
      parts. The most important changes in vibrational spectra caused by the anharmonic
      interactions could be reproduced with two and three atomic force field terms. The
      transfer scheme thus provides molecular anharmonic force fields without a
      significant loss of accuracy and brings significant savings of computer time and
      memory needed to generate molecular vibrational energies and spectra.

PMID- 20687644
TI  - Dissociation energy of the ground state of NaH.
AB  - The dissociation energy of the ground state of NaH was determined by analyzing
      the observed near dissociation rovibrational levels. These levels were reached by
      stimulated emission pumping and fluorescence depletion spectroscopy. A total of
      114 rovibrational levels in the ranges 9<or=v(")<or=21 and 1<or=J(")<or=14 were
      assigned to the X (1)Sigma(+) state of NaH. The highest vibrational level
      observed was only about 40 cm(-1) from the dissociation limit in the ground
      state. One quasibound state, above the dissociation limit and confined by the
      centrifugal barrier, was observed. Determining the vibrational quantum number at
      dissociation v(D) from the highest four vibrational levels yielded the
      dissociation energy D(e)=15 815+/-5 cm(-1). Based on new observations and
      available data, a set of Dunham coefficients and the rotationless Rydberg-Klein
      Rees curve were constructed. The effective potential curve and the quasibound
      states were discussed.

PMID- 20687645
TI  - Fivefold differential cross sections for ground-state ionization of aligned H(2)
      by electron impact.
AB  - We discuss the ionization of aligned hydrogen molecules into their ionic ground
      state by 200 eV electrons. Using a reaction microscope, the complete electron
      scattering kinematics is imaged over a large solid angle. Simultaneously, the
      molecular alignment is derived from postcollision dissociation of the residual
      ion. It is found that the ionization cross section is maximized for small angles
      between the internuclear axis and the momentum transfer. Fivefold differential
      cross sections (5DCSs) reveal subtle differences in the scattering process for
      the distinct alignments. We compare our observations with theoretical 5DCSs
      obtained with an adapted molecular three-body distorted wave model that
      reproduces most of the results, although discrepancies remain.

PMID- 20687646
TI  - Vibrationally resolved photoelectron imaging of gold hydride cluster anions: AuH(
      ) and Au(2)H(-).
AB  - Photoelectron spectra and angular distributions in photodetachment of gold
      hydride anions AuH(-) and Au(2)H(-) have been obtained using photoelectron
      velocity-map imaging. Both the images exhibit vibrationally resolved ground state
      transitions. The adiabatic electron affinities of AuH and Au(2)H are measured to
      be 0.758(20) and 3.437(3) eV, respectively. Franck-Condon analyses of the AuH
      spectra determined that the equilibrium bond length of the ground state of AuH(-)
      is 1.597(6) A. The photoelectron images of Au(2)H(-) show a vibrational
      progression of 148(4) cm(-1) assigned to the Au-Au stretching mode at the ground
      state. Ab initio calculation results are in excellent agreement with the
      experimental results. For the ground state of Au(2)H, a new bent Au-Au-H
      structure with the angle of 131 degrees is suggested. Moreover, energy-dependent
      photoelectron anisotropy parameters are also reported and discussed.

PMID- 20687647
TI  - Sound-driven fluid dynamics in pressurized carbon dioxide.
AB  - Using high-speed visualization we demonstrate that ultrasound irradiation of
      pressurized carbon dioxide (CO(2)) induces phenomena that do not occur in
      ordinary liquids at ambient conditions. For a near-critical mixture of CO(2) and
      argon, sonication leads to extremely fast local phase separation, in which the
      system enters and leaves the two-phase region with the frequency of the imposed
      sound field. This phase transition can propagate with the speed of sound, but can
      also be located at fixed positions in the case of a standing sound wave.
      Sonication of a vapor-liquid interface creates a fine dispersion of liquid and
      vapor, irrespective whether the ultrasound horn is placed in the liquid or the
      vapor phase. In the absence of an interface, sonication of the liquid leads to
      ejection of a macroscopic vapor phase from the ultrasound horn with a velocity of
      several meters per second in the direction of wave propagation. The findings
      reported here potentially provide a tunable and noninvasive means for enhancing
      mass and heat transfer in high-pressure fluids.

PMID- 20687648
TI  - Use of complex configuration interaction calculations and the stationary
      principle for the description of metastable electronic states of HCl(-).
AB  - The complex multireference single- and double-excitation configuration
      interaction method has been employed to compute potential curves for the anion of
      the hydrogen chloride molecule. First, conventional CI calculations with real
      basis functions have been carried out to determine the potential curves of both
      HCl and its anion over a large range of internuclear distance. It is shown that
      adding basis functions with very small exponents leads to sharply avoided
      crossings for the HCl(-) potentials that greatly complicate the search for
      resonance states thought to be responsible for features observed in electron
      collision experiments. By limiting the number of such diffuse-type functions it
      is possible to describe resonance states at a highly correlated level and still
      account for their interaction with the continuum in which they are embedded. In
      the present study of the HCl(-) anion the complex basis function technique of
      Moiseyev-Corcoran and McCurdy-Resigno is employed to calculate the energy
      positions and line-widths of the resonance states. Two states of (2)Sigma(+)
      symmetry are calculated which have potentials that have significantly different
      shapes than that of the neutral ground state and thus contribute to the cross
      section for vibrational excitation of the neutral HCl molecule induced by low
      energy electron collisions. The lower of these (1 (2)Sigma(+)) correlates
      smoothly with the bound anionic ground state at large internuclear distances and
      is seen to be responsible for the sharp peaks observed in the low-energy region
      of the spectrum. The upper state (3 (2)Sigma(+)) has a much larger bond length
      and is assigned to the broad bands observed with a maximum in the 2.5-3.0 eV
      range. The present calculations thus stand in contradiction to earlier claims
      that the above peaks are caused by so-called virtual states without a definite
      autoionization lifetime.

PMID- 20687649
TI  - Structure and spectroscopy of ground and excited states of LiYb.
AB  - Multireference configuration interaction and coupled cluster calculations have
      been carried out to determine the potential energy curves for the ground and low
      lying excited states of the LiYb molecule. The scalar relativistic effects have
      been included by means of the Douglas-Kroll Hamiltonian and effective core
      potential and the spin-orbit couplings have been evaluated by the full
      microscopic Breit-Pauli operator. The LiYb permanent dipole moment, static dipole
      polarizability, and Franck-Condon factors have been determined. Perturbations of
      the vibrational spectrum due to nonadiabatic interactions are discussed.

PMID- 20687650
TI  - IR spectra of protonated benzaldehyde clusters, C(7)H(7)O(+)-L(n)
      (L=Ar,N(2);n<or=2): Ion-ligand binding motifs of the cis and trans oxonium
      isomers.
AB  - Infrared photodissociation (IRPD) spectra of mass-selected protonated
      benzaldehyde (C(7)H(7)O(+),BZH(+)) and its weakly bound clusters with Ar and N(2)
      produced in an electron impact source are recorded in the C-H and O-H stretch
      ranges. The experimental results are supported by ab initio and density
      functional calculations. Analysis of the IRPD spectrum of the BZH(+) monomer is
      consistent with the presence of the cis and trans isomers of the oxonium ions,
      which is confirmed by the cluster spectra. No signature of the less stable
      carbenium ions is detected. Frequency shifts in the IRPD spectra of dimers and
      trimers provide information about the preferred intermolecular ligand binding
      site (pi-bonding versus H-bonding) and the corresponding interaction strength. H
      bonding to the OH group of the oxonium ions of BZH(+) is found to be favored over
      pi-bonding to the aromatic ring for both Ar and N(2). There are significant
      differences in the microsolvation structure and energetics of the cis and trans
      oxonium isomers of BZH(+) due to the rather different acidities of their OH
      groups and isomer-dependent effects arising from steric hindrance. The large
      positive partial charge of the protonated formyl group implies that the cluster
      growth of the larger clusters continues by further solvation of the protonated
      substituent rather than the aromatic ring.

PMID- 20687651
TI  - Cavity-enhanced resonant photoacoustic spectroscopy with optical feedback cw
      diode lasers: A novel technique for ultratrace gas analysis and high-resolution
      spectroscopy.
AB  - Cavity-enhanced resonant photoacoustic spectroscopy with optical feedback cw
      diode lasers (OF-CERPAS) is introduced as a novel technique for ultratrace gas
      analysis and high-resolution spectroscopy. In the scheme, a single-mode cw diode
      laser (3 mW, 635 nm) is coupled into a high-finesse linear cavity and stabilized
      to the cavity by optical feedback. Inside the cavity, a build-up of laser power
      to at least 2.5 W occurs. Absorbing gas phase species inside the cavity are
      detected with high sensitivity by the photoacoustic effect using a microphone
      embedded in the cavity. To increase sensitivity further, coupling into the cavity
      is modulated at a frequency corresponding to a longitudinal resonance of an organ
      pipe acoustic resonator (f=1.35 kHz and Q approximately 10). The technique has
      been characterized by measuring very weak water overtone transitions near 635 nm.
      Normalized noise-equivalent absorption coefficients are determined as alpha
      approximately 4.4x10(-9) cm(-1) s(1/2) (1 s integration time) and 2.6x10(-11) cm(
      1) s(1/2) W (1 s integration time and 1 W laser power). These sensitivities
      compare favorably with existing state-of-the-art techniques. As an advantage, OF
      CERPAS is a "zero-background" method which increases selectivity and sensitivity,
      and its sensitivity scales with laser power.

PMID- 20687652
TI  - Ligand effect on uranium isotope fractionations caused by nuclear volume effects:
      An ab initio relativistic molecular orbital study.
AB  - We have calculated the nuclear volume term (ln K(nv)) of the isotope
      fractionation coefficient (epsilon) between (235)U-(238)U isotope pairs by
      considering the effect of ligand coordination in a U(IV)-U(VI) reaction system.
      The reactants were modeled as [UO(2)Cl(3)](-) and [UO(2)Cl(4)](2-) for U(VI), and
      UCl(4) for U(IV). We adopted the Dirac-Coulomb Hartree-Fock method with the
      Gaussian-type finite nucleus model. The result obtained was ln K(nv)=0.001 90 at
      308 K, while the experimentally estimated value of ln K(nv) is 0.002 24. We also
      discuss how the ligand affects the value of ln K(nv), especially for the various
      structures of different compounds, and different ligands within the halogen ion
      series (F, Cl, and Br).

PMID- 20687653
TI  - Spectroscopic study of CHBrF(2) up to 9500 cm(-1): Vibrational analysis,
      integrated band intensities, and ab initio calculations.
AB  - The gas-phase infrared spectra of bromodifluoromethane, CHBrF(2), have been
      examined at medium resolution in the range of 200-9500 cm(-1). The assignment of
      the absorptions in terms of fundamental, overtone, combination, and hot bands,
      assisted by quantum chemical calculations is consistent all over the region
      investigated. Accurate values of integrated band intensities have also been
      determined for the first time in the range of 500-6000 cm(-1). Structural and
      molecular spectroscopic properties have been calculated at high level of theory.
      The coupled cluster CCSD(T) method in conjunction with a hierarchical series of
      correlation consistent basis sets has been employed and extrapolation to complete
      basis set has been considered for the equilibrium geometry. Vibrational analysis
      based on the second order perturbation theory has been carried out with the ab
      initio anharmonic force constants calculated using the second order Moller
      Plesset perturbation as well as coupled cluster [CCSD(T)] theory. A good
      agreement between the computed and the experimental data also including the
      integrated infrared band intensities has been obtained.

PMID- 20687654
TI  - Cross sections for rotational decoherence of perturbed nitrogen measured via
      decay of laser-induced alignment.
AB  - We quantitatively determine cross sections for rotational decoherence from the
      decay of nonadiabatic laser-induced alignment in nitrogen and nitrogen-foreign
      gas mixtures in a temperature range between 80 K and room temperature. The cross
      section for rotational decoherence in pure nitrogen decreases from 102 A(2) at 80
      K to 48 A(2) at 295 K, leading to long-lived coherences even at high
      temperatures. Comparison with the broadening of the transition lines of the Raman
      Q-branch reported in the literature shows that the decay of rotational coherence
      proceeds at the same rate as rotational depopulation. This is verified also for
      mixtures of nitrogen with hydrogen, helium, argon, and krypton. We discuss limits
      posed by a possible J-dependence of the cross sections and strategies for state
      resolved determination from the time-dependent alignment signal.

PMID- 20687655
TI  - Finite temperature quantum statistics of H(3) (+) molecular ion.
AB  - Full quantum statistical NVT simulation of the five-particle system H(3) (+) has
      been carried out using the path integral Monte Carlo method. Structure and
      energetics are evaluated as a function of temperature up to the thermal
      dissociation limit. The weakly density dependent dissociation temperature is
      found to be around 4000 K. Contributions from the quantum dynamics and thermal
      motion are sorted out by comparing differences between simulations with quantum
      and classical nuclei. The essential role of the quantum description of the
      protons is established.

PMID- 20687656
TI  - Comparisons of classical and Wigner sampling of transition state energy levels
      for quasiclassical trajectory chemical dynamics simulations.
AB  - Quasiclassical trajectory calculations are compared, with classical and Wigner
      sampling of transition state (TS) energy levels, for C(2)H(5)F( not equal)-
      >HF+C(2)H(4) product energy partitioning and [Cl...CH(3)...Cl](-) central barrier
      dynamics. The calculations with Wigner sampling are reported here for comparison
      with the previously reported calculations with classical sampling [Y. J. Cho et
      al., J. Chem. Phys. 96, 8275 (1992); L. Sun and W. L. Hase, J. Chem. Phys. 121,
      8831 (2004)]. The C(2)H(5)F( not equal) calculations were performed with direct
      dynamics at the MP2/6-31G( *) level of theory. Classical and Wigner sampling give
      post-transition state dynamics, for these two chemical systems, which are the
      same within statistical uncertainties. This is a result of important equivalences
      in these two sampling methods for selecting initial conditions at a TS. In
      contrast, classical and Wigner sampling often give different photodissociation
      dynamics [R. Schinke, J. Phys. Chem. 92, 3195 (1988)]. Here the sampling is
      performed for a vibrational state of the ground electronic state potential energy
      surface (PES), which is then projected onto the excited electronic state's PES.
      Differences between the ground and the excited PESs may give rise to
      substantially different excitations of the vibrational and dissociative
      coordinates on the excited state PES by classical and Wigner sampling, resulting
      in different photodissociation dynamics.

PMID- 20687657
TI  - Microscopic dynamics of supercooled low weight alcohols.
AB  - Dynamical properties of low weight alcohols have been analyzed both in the liquid
      and the supercooled states. Realistic interatomic potential models for methanol
      and ethanol have been used. The influence of temperature on the hydrogen-bonded
      structure has been undertaken. Remarkable similarities have been obtained in both
      systems. Velocity autocorrelation functions have been evaluated for molecules
      participating in zero, one, and two hydrogen bonds at a wide range of
      temperatures. A backscattering area preceded by a shoulder has been identified as
      a signature of this function when evaluated for the subset of molecules that
      participate in two hydrogen bonds. Memory functions have also been evaluated.
      Their initial decay depends only slightly upon temperature. A more marked
      temperature dependence is observed for the nonassociated molecules. For them,
      reasonable agreement with the mode-coupling approach predictions has been
      encountered.

PMID- 20687658
TI  - Resummed thermodynamic perturbation theory for central force associating
      potential: One-patch model.
AB  - A resummed thermodynamic perturbation theory for associating fluids with multiply
      bondable central force associating potential is proposed. We consider a simple
      one-patch model for associating fluids. The model is represented by the hard
      sphere system with a circular attractive patch on the surface of each hard
      sphere. Resummation is carried out to account for the blocking effects, i.e.,
      when the bonding of a particle restricts (blocks) its ability to bond with other
      particles. Closed form analytical expressions for thermodynamical properties
      (Helmholtz free energy, pressure, internal energy, and chemical potential) of the
      model with a doubly bondable patch at all degrees of the blockage are presented.
      In the limiting case of total blockage, when the particles become only singly
      bondable, our theory reduces to Wertheim's thermodynamic perturbation theory for
      dimerizing fluids. To validate the accuracy of the theory we compare to exact
      values, for the thermodynamical properties of the system, as determined by Monte
      Carlo computer simulations. In addition we compare the fraction of multiply
      bonded particles at different values of the density and temperature. Very good
      agreement between predictions of the theory, corrected for ring formation, and
      Monte Carlo computer simulation values was found in all cases studied. Less
      accurate are the original versions of the theory and Wertheim's thermodynamic
      perturbation theory for dimerization, especially at lower temperatures and larger
      sizes of the attractive patch.

PMID- 20687659
TI  - Brillouin scattering study of liquid methane under high pressures and high
      temperatures.
AB  - Brillouin scattering measurements were performed on liquid methane using diamond
      anvil cell along five isotherms and at the pressures up to solidification points.
      Sound velocity, refractive index, and adiabatic bulk modulus of liquid methane as
      function of pressure were determined with the measurements from the platelet and
      backscattering geometries. The maximum pressure and temperature reached up to
      5.12 GPa and 539 K. The sound velocity, refractive index, and adiabatic bulk
      modulus increased with pressure along each isotherm. The equation of state of
      liquid methane was determined from the present Brillouin results.

PMID- 20687660
TI  - Exciton localization in disordered poly(3-hexylthiophene).
AB  - Singlet exciton localization in conformationally disordered poly(3
      hexylthiophene) (P3HT) is investigated via configuration interaction (singles)
      calculations of the Pariser-Parr-Pople model. The P3HT structures are generated
      by molecular dynamics simulations. The lowest-lying excitons are spatially
      localized, space filling, and nonoverlapping. These define spectroscopic segments
      or chromophores. The strong conformational disorder in P3HT causes breaks in the
      pi-conjugation. Depending on the relative values of the disorder-induced
      localization length and the distances between the pi-conjugation breaks, these
      breaks sometimes serve to pin the low-lying localized excitons. The exciton
      confinement also causes a local spectrum of low-lying exciton states. Coulomb
      induced intra- or interchain interactions between spectroscopic segments in close
      spatial proximity can delocalize an exciton across these segments, in principle
      causing phase coherent transition dipole moments.

PMID- 20687661
TI  - Effect of state-selective reactive decay on the evolution of quantum systems.
AB  - The effect of state-selective reactive decay on the relaxation kinetics of
      quantum multistate systems is studied in detail in the Bloch-Redfield approach
      (BRA). The results are applied to the analysis of this effect in radical pair
      recombination kinetics. The BRA is shown to be able to describe quantitatively
      most important specific features of the recombination kinetics including those
      predicted by phenomenological treatment and by recently proposed approaches based
      on quantum measurement theories.

PMID- 20687662
TI  - Spatial averaging for small molecule diffusion in condensed phase environments.
AB  - Spatial averaging is a new approach for sampling rare-event problems. The
      approach modifies the importance function which improves the sampling efficiency
      while keeping a defined relation to the original statistical distribution. In
      this work, spatial averaging is applied to multidimensional systems for typical
      problems arising in physical chemistry. They include (I) a CO molecule diffusing
      on an amorphous ice surface, (II) a hydrogen molecule probing favorable positions
      in amorphous ice, and (III) CO migration in myoglobin. The systems encompass a
      wide range of energy barriers and for all of them spatial averaging is found to
      outperform conventional Metropolis Monte Carlo. It is also found that optimal
      simulation parameters are surprisingly similar for the different systems studied,
      in particular, the radius of the point cloud over which the potential energy
      function is averaged. For H(2) diffusing in amorphous ice it is found that facile
      migration is possible which is in agreement with previous suggestions from
      experiment. The free energy barriers involved are typically lower than 1
      kcal/mol. Spatial averaging simulations for CO in myoglobin are able to locate
      all currently characterized metastable states. Overall, it is found that spatial
      averaging considerably improves the sampling of configurational space.

PMID- 20687663
TI  - An analysis of the NEXAFS spectra of a molecular crystal: alpha-glycine.
AB  - The nitrogen K-edge near edge x-ray absorption fine structure spectrum of alpha
      crystalline glycine has been calculated for temperatures ranging from 0 to 450 K.
      Significant temperature dependent spectral changes are predicted. The calculated
      room temperature spectrum is in good agreement with the experiment. At high
      temperatures, molecular motions strongly influence the spectrum, as any unique
      spectrum from an individual instantaneous configuration does not resemble the
      experimental result or the average calculated spectrum; complex coupled motions
      in this prototypical molecular crystal underlie the observed spectral changes.

PMID- 20687664
TI  - Study of the sticking of a hydrogen atom on a graphite surface using a mixed
      classical-quantum dynamics method.
AB  - The sticking of one hydrogen atom chemisorbed on the (0001) graphite surface is
      investigated using a mixed classical-quantum method. The phonon modes of the
      system in the collinear scattering approach are included in the dynamics
      calculations. The vibrational degrees of freedom of the surface (phonons) are
      treated classically, while the H-surface motion is treated using a one
      dimensional quantum wave packet propagation method. The sticking probabilities
      are calculated and the individual contributions of the phonon bands to the
      collision dynamics are analyzed for surface temperatures of 10, 150, and 300 K
      and hydrogen kinetic energies ranging from 0.13 to 1.08 eV. An analytical form of
      the sticking probability as a function of the surface temperature is also
      proposed.

PMID- 20687665
TI  - Density functional theory based molecular dynamics study of hydration and
      electronic properties of aqueous La(3+).
AB  - Structural and electronic properties of La(3+) immersed in bulk water have been
      assessed by means of density functional theory (DFT)-based Car-Parrinello
      molecular dynamics (CPMD) simulations. Correct structural properties, i.e.,
      La(III)-water distances and La(III) coordination number, can be obtained within
      the framework of Car-Parrinello simulations providing that both the La
      pseudopotential and conditions of the dynamics (fictitious mass and time step)
      are carefully set up. DFT-MD explicitly treats electronic densities and is shown
      here to provide a theoretical justification to the necessity of including
      polarization when studying highly charged cations such as lanthanoids(III) with
      classical MD. La(3+) was found to strongly polarize the water molecules located
      in the first shell, giving rise to dipole moments about 0.5 D larger than those
      of bulk water molecules. Finally, analyzing Kohn-Sham orbitals, we found La(3+)
      empty 4f orbitals extremely compact and to a great extent uncoupled from the
      water conduction band, while the 5d empty orbitals exhibit mixing with unoccupied
      states of water.

PMID- 20687666
TI  - The boson peak of silicate glasses: the role of Si-O, Al-O, and Si-N bonds.
AB  - The role of Si-O, Al-O, and Si-N bonds on the boson peak of silicate glasses has
      been investigated from a study of amorphous Si, SiO(2), and two calcium
      aluminosilicates with 0 (Ca28-O) and 4.4 (Ca28-N) mol % Si(3)N(4). The low
      frequency part of the vibrational density of states g(omega) has been calculated
      from inversion of literature data and new heat capacity measurements. As defined
      by g(omega)/omega(2), the boson peak correlates with the excess heat capacity
      observed with respect to Debye T(3) limiting law. That libration of SiO(4)
      tetrahedra represents the main source of low-frequency excitations in silica
      glass is illustrated by the strong difference between the anomalies of amorphous
      Si and SiO(2) glass and the marked decrease observed for SiO(2) phases of
      increasing density. When Al substitutes for Si, libration of AlO(4) tetrahedra
      appears hampered by the presence of a charge-compensating cation. Rigidification
      of the silicate network resulting from substitution of N for O causes the boson
      peak of Ca28-N to be smaller than that of Ca28-O and shifted toward higher
      frequencies as increased cross-linking hinders libration of SiO(4) or AlO(4)
      tetrahedra. In agreement with their universal phenomenology, the calorimetric
      boson anomalies of Ca28-O and Ca28-N plot on the master curve defined previously
      by SiO(2) and alkali silicate glasses.

PMID- 20687667
TI  - Multi-time density correlation functions in glass-forming liquids: Probing
      dynamical heterogeneity and its lifetime.
AB  - A multi-time extension of a density correlation function is introduced to reveal
      temporal information about dynamical heterogeneity in glass-forming liquids. We
      utilize a multi-time correlation function that is analogous to the higher-order
      response function analyzed in multidimensional nonlinear spectroscopy. Here, we
      provide comprehensive numerical results of the four-point, three-time density
      correlation function from longtime trajectories generated by molecular dynamics
      simulations of glass-forming binary soft-sphere mixtures. We confirm that the two
      dimensional representations in both time and frequency domains are sensitive to
      the dynamical heterogeneity and that these reveal the couplings of correlated
      motions, which exist over a wide range of time scales. The correlated motions
      detected by the three-time correlation function are divided into mobile and
      immobile contributions that are determined from the particle displacement during
      the first time interval. We show that the peak positions of the correlations are
      in accord with the information on the non-Gaussian parameters of the van Hove
      self-correlation function. Furthermore, it is demonstrated that the progressive
      changes in the second time interval in the three-time correlation function enable
      us to analyze how correlations in dynamics evolve in time. From this analysis, we
      evaluated the lifetime of the dynamical heterogeneity and its temperature
      dependence systematically. Our results show that the lifetime of the dynamical
      heterogeneity becomes much slower than the alpha-relaxation time that is
      determined from the two-point density correlation function when the system is
      highly supercooled.

PMID- 20687668
TI  - Cubic gauche-CN: A superhard metallic compound predicted via first-principles
      calculations.
AB  - In this paper, we suggest a novel potential superhard material, a new carbon
      nitride phase consisted of sp(3) hybridized bonds, possessing a cubic P2(1)3
      symmetry (8 atoms/cell, labeled by cg-CN) which is similar to cubic gauche
      nitrogen (cg-N) by first-principles calculations. It is a metallic compound,
      while most of other superhard materials are insulators or semiconductors. The
      Vickers hardness of cg-CN is 82.56 GPa, and if we considered the negative effect
      of metallic component on hardness, it is 54.7 GPa, which is much harder than any
      other metallic materials. It is found that a three-dimensional C-N network is
      mainly responsible for the high hardness. Both elastic constant and phonon
      dispersion calculations show that this structure remains mechanically and
      dynamically stable in the pressure ranges from 0 to 100 GPa. Furthermore, we
      compared our results with many other proposed structures of carbon nitride with
      1:1 stoichiometry and found that only cg-CN is the most favorable stable crystal
      structure. Formation enthalpies calculations demonstrate that this material can
      be synthesizable at high pressure (12.7-36.4 GPa).

PMID- 20687669
TI  - Evolution of the isotropic to nematic phase transition in binary mixtures of
      octylcyanobiphenyl and n-hexane.
AB  - High-resolution calorimetry has been performed to study the effect of dilution by
      a nonmesogenic, low-molecular weight solvent (linear n-hexane) on the isotropic
      nematic (I-N) phase transition in the liquid crystal (LC) octylcyanobiphenyl
      (8CB) as a function of n-hexane concentration. Numerous temperature scans were
      performed without continuous mixing for pure 8CB and all mixture samples of n
      hexane mole fraction ranging from x(hex)=0.02 to 0.12. The I-N specific heat peak
      remains first-order for all samples and shifts toward lower temperature
      nonlinearly while the two-phase I+N coexistence width broadens linearly with
      increasing x(hex). Multiple heating and cooling scans are reproducible and
      indicate phase separation, if it occurs, must be on very short length scales and
      is reversible. These results may be a consequence of a competition between random
      dilution effects and the tendency to phase separate. It is shown that solvent
      dilution of a LC, if miscible and depending on solvent structure, can lead to a
      controlled altering of the intermolecular potentials and softening of the LC
      viscoelastic properties.

PMID- 20687670
TI  - Stress-strain relation in the collapse of Langmuir monolayer of a dimer of disk
      shaped moiety.
AB  - Langmuir monolayer of a novel molecule containing dimer of disk shaped moiety,
      viz., terephtalic acid bis-[6-(3,6,7,10,11-pentahexyloxy-triphenylen-2-yloxyl)
      hexyl] ester (tp-dimer), was studied at air-water interface. The monolayer of the
      tp-dimer at air-water interface exhibited the coexistence of condensed and gas
      phases at large area per molecule which on compression transformed to a uniform
      condensed phase at lower area per molecule (1.80 nm(2)) and then collapsed at
      1.67 nm(2). The monolayer film transferred by Langmuir-Blodgett technique onto a
      hydrophilic silicon substrate was studied using an atomic force microscope. The
      topography image showed the film to be of height of about 1.5 nm corresponding to
      the edge-on configuration of the triphenylene moieties. We have studied the
      collapse of monolayer at air-water interface as a function of compression rate
      and temperature. We find that the collapse pressure increased with increase in
      the compression rate. The surface pressure of the monolayer is considered as
      stress and compression as strain. The strain rate is related to the collapse
      pressure by a power law similar to that found in the dendrimers. Our studies on
      the effect of temperature on the collapse pressure of tp-dimer monolayer showed
      that the collapse pressure decreased with increase in temperature. We have
      considered the Arrhenius temperature dependence of the strain rate and calculated
      the activation energy for the collapse of monolayer. Our analysis of the relative
      area loss as a function of time in the collapse region suggests that the
      monolayer collapses by the formation of nuclei of three-dimensional crystallites.

PMID- 20687671
TI  - Observation of surface structure of 1-alkyl-3-methylimidazolium
      bis(trifluoromethanesulfonyl)imide using high-resolution Rutherford
      backscattering spectroscopy.
AB  - The surface structures of 1-alkyl-3-methylimidazolium
      bis(trifluoromethanesulfonyl)imide ([C(n)MIM][TFSI], n=2,4,6) are studied by high
      resolution Rutherford backscattering spectroscopy. The average composition of the
      surface molecular layer is very close to the stoichiometric composition, showing
      that neither ion is enriched in the surface layer. A detailed analysis indicates
      that both cations and anions have preferential molecular orientations at the
      surface. The alkyl chains of the [C(n)MIM] cations protrude to the vacuum and the
      CF(3) groups of the [TFSI] anions are also pointing toward the vacuum. While the
      orientation of the [TFSI] anion becomes weaker with increasing alkyl-chain
      length, the protrusion of the alkyl chain occurs irrespective of the chain
      length. It was also found that the N(SO(2))(2) moiety is located nearly at the
      same depth as the imidazolium ring, suggesting that one of oxygen atoms in [TFSI]
      is bonded to the hydrogen of the C(2) carbon atom of the imidazolium ring.

PMID- 20687672
TI  - Hysteresis reversion in graphene field-effect transistors.
AB  - To enhance performances of graphene/SiO(2) based field-effect transistors (FETs),
      understanding of the transfer of carriers through the graphene/SiO(2) interface
      is crucial. In this paper, we have studied the temperature dependent transfer
      characters of graphene FETs. Hysteresis loop is shown to be dominated by
      trapping/detrapping carriers through the graphene/SiO(2) interface.

PMID- 20687673
TI  - A thermodynamically consistent determination of surface tension of small Lennard
      Jones clusters from simulation and theory.
AB  - We have determined the surface tension of small Lennard-Jones clusters using
      molecular dynamics and Monte Carlo simulation methods as well as density
      functional theory calculations. For the two simulation methods the surface
      tension is calculated via a rigorous thermodynamic route using simulation data as
      input. The capillary approximation of the classical nucleation theory, where the
      surface tension of a planar surface is used for cluster surface, is found to be
      quite reasonable even when the cluster size is as small as 100-150 atoms. For
      smaller cluster sizes the cluster surface tension is considerably lower than the
      planar value. We have also obtained an approximative value for the Tolman length
      by extrapolating to the planar limit the difference between the equimolar radius
      and the radius of the surface of tension. A negative Tolman length is suggested
      by all the methods used.

PMID- 20687675
TI  - Stability of critical bubble in stretched fluid of square-gradient density
      functional model with triple-parabolic free energy.
AB  - The square-gradient density-functional model with triple-parabolic free energy,
      which was used previously to study the homogeneous bubble nucleation [M.
      Iwamatsu, J. Chem. Phys. 129, 104508 (2008)], is used to study the stability of
      the critical bubble nucleated within the bulk undersaturated stretched fluid. The
      stability of the bubble is studied by solving the Schrodinger equation for the
      fluctuation. The negative eigenvalue corresponds to the unstable growing mode of
      the fluctuation. Our results show that there is only one negative eigenvalue
      whose eigenfunction represents the fluctuation that corresponds to the
      isotropically growing or shrinking nucleus. In particular, this negative
      eigenvalue survives up to the spinodal point. Therefore, the critical bubble is
      not fractal or ramified near the spinodal.

PMID- 20687674
TI  - Noninvasive bipolar double-pulsed-field-gradient NMR reveals signatures for pore
      size and shape in polydisperse, randomly oriented, inhomogeneous porous media.
AB  - Noninvasive characterization of pore size and shape in opaque porous media is a
      formidable challenge. NMR diffusion-diffraction patterns were found to be
      exceptionally useful for obtaining such morphological features, but only when
      pores are monodisperse and coherently placed. When locally anisotropic pores are
      randomly oriented, conventional diffusion NMR methods fail. Here, we present a
      simple, direct, and general approach to obtain both compartment size and shape
      even in such settings and even when pores are characterized by internal field
      gradients. Using controlled porous media, we show that the bipolar-double-pulsed
      field-gradient (bp-d-PFG) methodology yields diffusion-diffraction patterns from
      which pore size can be directly obtained. Moreover, we show that pore shape,
      which cannot be obtained by conventional methods, can be directly inferred from
      the modulation of the signal in angular bp-d-PFG experiments. This new
      methodology significantly broadens the types of porous media that can be studied
      using noninvasive diffusion-diffraction NMR.

PMID- 20687676
TI  - Adsorption and switching properties of a N-benzylideneaniline based molecular
      switch on a Au(111) surface.
AB  - High resolution electron energy loss spectroscopy has been employed to analyze
      the adsorption geometry and the photoisomerization ability of the molecular
      switch carboxy-benzylideneaniline (CBA) adsorbed on Au(111). CBA on Au(111)
      adopts a planar (trans) configuration in the first monolayer (ML) as well as for
      higher coverages (up to 6 ML), in contrast to the strongly nonplanar geometry of
      the molecule in solution. Illumination with UV light of CBA in direct contact
      with the Au(111) surface (<or=1 ML) caused no changes in the vibrational
      structure, whereas at higher coverages (>1 ML) pronounced modifications of
      vibrational features were observed, which we assign to a trans-->cis
      isomerization. Thermal activation induced the back reaction to trans-CBA. We
      propose that the photoisomerization is driven by a direct (intramolecular)
      electronic excitation of the adsorbed CBA molecules in the second ML (and above)
      analogous to CBA in the liquid phase.

PMID- 20687677
TI  - Edge versus interior in the chemical bonding and magnetism of zigzag edged
      triangular graphene molecules.
AB  - Ab initio density functional theory calculations show that the CC bond lengths
      fall into three distinct groups: core, apex, and edge, irrespective of whether
      the molecular center is a single atom or a C(6)-ring. The core, with a geometry
      that approximates infinite graphene, extends to the penultimate triangular row of
      carbon atoms, except in the vicinity of an apex. Impressed on the core bonds
      starting at the center is a small increasing length oscillation. The perimeter CC
      bonds joined at the apex are the shortest in the molecule. The edge carbon atoms
      are separated from interior atoms by the longest bonds in the molecule. The spin
      density localized primarily on edge (not apex) carbons with attached hydrogen (A
      sublattice) is likely the highest attainable in any graphene molecule. The CC
      bonds in the high spin section of the edges are uniform in length and longer than
      perimeter CC bonds in the zigzag edged linear acenes, hexangulenes, annulenes,
      and benzene. This is attributed to the large number of edge localized nonbonding
      molecular orbitals (NBMOs) that sequestered pi-charge making it unavailable for
      bonding.

PMID- 20687678
TI  - Energy barrier of proton transfer at ice surfaces.
AB  - We estimated the energy barrier of proton transfer on ice film surfaces through
      the measurement of the H/D exchange kinetics of H(2)O and D(2)O molecules. The
      isotopomeric populations of water molecules and hydronium ions on the surface
      were monitored by using the techniques of reactive ion scattering and low energy
      sputtering, respectively, along the progress of the H/D reaction. When hydronium
      ions were externally added onto an ice film at a temperature of 70 K, a proton
      was transferred from the hydronium ion mostly to an adjacent water molecule. The
      proton transfer distance and the H/D exchange rate increased as the temperature
      increased for 90-110 K. The activation energy of the proton transfer was
      estimated to be 10+/-3 kJ mol(-1) on a polycrystalline ice film grown at 135 K.
      The existence of a substantial energy barrier for proton transfer on the ice
      surface agreed with proton stabilization at the surface. We also examined the H/D
      exchange reaction on a pure ice film surface at temperatures of 110-130 K. The
      activation energy of the reaction was estimated to be 17+/-4 kJ mol(-1), which
      was contributed from the ion pair formation and proton transfer processes on the
      surface.

PMID- 20687679
TI  - Kinetic Monte Carlo simulations of anisotropic Si(100) etching: Modeling the
      chemical origins of characteristic etch morphologies.
AB  - An atomistic, chemically realistic, kinetic Monte Carlo simulator of anisotropic
      Si(100) etching was developed. Surface silicon atoms were classified on the basis
      of their local structure, and all atoms of each class were etched with the same
      rate. A wide variety of morphologies, including rough, striped, and hillocked,
      was observed. General reactivity trends were correlated with specific
      morphological features. The production of long rows of unstrained dihydride
      species, recently observed in NH(4)F (aq) etching of Si(100), could only be
      explained by the rapid etching of dihydrides that are adjacent to (strained)
      monohydrides-so-called "alpha-dihydrides." Some etch kinetics promoted the
      formation of {111}-microfaceted pyramidal hillocks, similar in structure to those
      observed experimentally during Si(100) etching. Pyramid formation was intrinsic
      to the etch kinetics. In contrast with previously postulated mechanisms of
      pyramid formation, no masking agent (e.g., impurity, gas bubble) was required.
      Pyramid formation was explained in terms of the slow etch rate of the {111}
      sides, {110} edges, and the dihydride species that terminated the apex of the
      pyramid. As a result, slow etching of Si(111) surfaces was a necessary, but
      insufficient, criterion for microfacet formation on Si(100) surfaces.

PMID- 20687680
TI  - Second-harmonic generation in conjugated polymer films: A sensitive probe of how
      bulk polymer crystallinity changes with spin speed.
AB  - In this paper, we examine the second-harmonic generation (SHG) from spin-cast
      films of the conjugated polymer poly(2-methoxy-5-(2(')-ethylhexyloxy)para
      phenylenevinylene) (MEH-PPV). We find that the SHG intensity depends strongly on
      the speed used to spin cast the films. Two-dimensional grazing incidence x-ray
      diffraction (XRD) experiments show that the bulk crystallinity of the MEH-PPV
      films varies in the same way with spin speed as the SHG intensity. This strongly
      suggests that instead of being interface specific, the second-harmonic signal
      from conjugated polymer films is dominated by the crystalline domains in the
      bulk. The nonmonotonic dependence of both the SHG intensity and the degree of MEH
      PPV crystallinity results from a competition between the shear forces and the
      solvent evaporation rate during spin coating, which produces a maximum degree of
      crystallinity for MEH-PPV films spin cast at around 1400 rpm. We also use XRD to
      show that thermal annealing produces MEH-PPV films with a single degree of bulk
      crystallinity, independent of how they were originally cast. This allows us to
      model the angle- and thickness-dependent SHG from annealed MEH-PPV films with a
      single polarizability tensor. We find that the SHG from MEH-PPV films fits best
      to a bulk-allowed electric quadrupole mechanism, consistent with the bulk SHG
      seen in other pi-stacked aromatic molecules. Thus, rather than providing
      information about conjugated polymer interfaces, SHG can be used as a sensitive
      probe of the local degree of crystallinity in the bulk of conjugated polymer
      films.

PMID- 20687681
TI  - Isomerization-induced surface relief gratings formation: A comparison between the
      probe and the matrix dynamics.
AB  - We report molecular dynamics simulations of the effect of the photoisomerization
      of probe molecules on the nonequilibrium dynamics of a bulk amorphous matrix. Is
      it the matrix or the probe that drives the dynamics in SRG formation? In the
      first picture, the probe isomerization induces the motion of the probe inside the
      matrix. The motion of the probe then induces molecular motions inside the matrix.
      In the second picture, the probe isomerization induces a modification of the
      matrix diffusion mechanism. The diffusion of the matrix then induces the motion
      of the embedded probe. To answer this question, we compare the motion of the
      probe molecules and the motion of the matrix molecules in various thermodynamic
      conditions. We show that when the isomerization is switched on, the matrix
      molecules surrounding the probe move faster than the probe. Around the probe, the
      structural relaxation time of the matrix molecules is shorter than the probe
      relaxation time and the diffusion of the matrix molecules is larger than the
      probe diffusion. These results show that the matrix motions drive the dynamics.

PMID- 20687682
TI  - Properties of knotted ring polymers. I. Equilibrium dimensions.
AB  - We report calculations on three classes of knotted ring polymers: (1) simple
      cubic lattice self-avoiding rings (SARs), (2) "true" theta-state rings, i.e.,
      SARs generated on the simple-cubic lattice with an attractive nearest-neighbor
      contact potential (theta-SARs), and (3) ideal, Gaussian rings. Extrapolations to
      large polymerization index N imply knot localization in all three classes of
      chains. Extrapolations of our data are also consistent with conjectures found in
      the literature which state that (1) R(g)-->AN(nu) asymptotically for ensembles of
      random knots restricted to any particular knot state, including the unknot; (2) A
      is universal across knot types for any given class of flexible chains; and (3) nu
      is equal to the standard self-avoiding walk (SAW) exponent (congruent with 0.588)
      for all three classes of chains (SARs, theta-SARs, and ideal rings). However,
      current computer technology is inadequate to directly sample the asymptotic
      domain, so that we remain in a crossover scaling regime for all accessible values
      of N. We also observe that R(g) approximately p(-0.27), where p is the "rope
      length" of the maximally inflated knot. This scaling relation holds in the
      crossover regime, but we argue that it is unlikely to extend into the asymptotic
      scaling regime where knots become localized.

PMID- 20687683
TI  - Properties of knotted ring polymers. II. Transport properties.
AB  - We have calculated the hydrodynamic radius R(h) and intrinsic viscosity [eta] of
      both lattice self-avoiding rings and lattice theta-state rings that are confined
      to specific knot states by our path-integration technique. We observe that naive
      scaling arguments based on the equilibrium polymer size fail for both the
      hydrodynamic radius and the intrinsic viscosity, at least over accessible chain
      lengths. (However, we do conjecture that scaling laws will nevertheless prevail
      at sufficiently large N.) This failure is attributed to a "double" cross-over.
      One cross-over effect is the transition from delocalized to localized knotting:
      in short chains, the knot is distributed throughout the chain, while in long
      chains it becomes localized in only a portion of the chain. This transition
      occurs slowly with increasing N. The other cross-over, superimposed upon the
      first, is the so-called "draining" effect, in which transport properties maintain
      dependence on local structure out to very large N. The hydrodynamic mobility of
      knotted rings of the same length and backbone structure is correlated with the
      average crossing number X of the knots. The same correlation between mobility and
      knot complexity X has been observed for the gel-electrophoretic mobility of
      cyclic DNA molecules.

PMID- 20687684
TI  - Effect of residual attractive interactions in size asymmetric colloidal mixtures:
      Theoretical analysis and predictions.
AB  - We analyze the influence of residual attractions on the static and some dynamic
      properties of size asymmetric mixtures of "hard-sphere-like" colloids. These
      attractions, usually neglected in the theoretical analysis, are characterized by
      a very short range and a moderate strength reflecting the underlying microscopic
      structure of the colloidal particles. Their effect on the potentials of mean
      force is analyzed from analytical expressions obtained from low density
      expansions. The effective potential of the big particle fluid is next considered.
      An analytical expression is proposed for estimating the deviation with respect to
      the hard sphere depletion potential. This case is compared to that of mixtures
      with noninteracting depletants. The important consequences on the binodals and
      the glass transition lines of the effective fluid are discussed in both cases.
      This study is next extended to other properties-the specific heat and the low
      shear viscosity-which incorporate contributions from the two components of the
      binary mixture.

PMID- 20687685
TI  - Electrostatic origins of polyelectrolyte adsorption: Theory and Monte Carlo
      simulations.
AB  - Electrostatic interactions may promote or abate polyelectrolyte adsorption onto a
      charged surface depending on a number of interrelated factors including the
      surface and polymer charge densities, the salt concentration, and
      nonelectrostatic interactions such as van der Waals and hydrophobic forces. Even
      without the nonelectrostatic interactions, the electrostatic behavior of
      polyelectrolyte systems is often counterintuitive and cannot be explained with
      conventional theories of polymers or simple electrolytes. In this work, a
      nonlocal density functional theory (NLDFT) and Monte Carlo simulations are used
      together to investigate polyelectrolyte adsorption at both oppositely charged and
      like-charged surfaces (one due to the direct electrostatic attraction and the
      other due to counterion correlations). The simulation results provide a stringent
      test of the numerical performance of the NLDFT, in particular for systems
      containing multivalent counterions where electrostatic correlations are
      important. A systematic study of the effects of ion valence, salt concentration,
      and polyion chain length reveals that polyelectrolyte attraction to an oppositely
      charged surface is nearly a neutralization effect, little influenced by the
      polyion chain length and counterion valence. Neither the surface mean
      electrostatic potential nor the integrated local charge density shows no
      significant sign of charge inversion. Both theory and simulation predict
      polyelectrolyte adsorption onto a like-charged surface when the system contains
      multivalent counterions. In that case, the surface excess is sensitive to the
      surface charge density, the counterion valence, and the salt concentration. The
      surface mean electrostatic potential shows a clear evidence of charge inversion
      when two layers of like charges are mediated by multivalent counterions. The
      theoretical investigations indicate that most likely, the electrostatic
      correlation mediated by multivalent counterions is responsible for the layer-by
      layer assembly of oppositely charged polyelectrolyte films.

PMID- 20687686
TI  - Linear viscoelasticity of a single semiflexible polymer with internal friction.
AB  - The linear viscoelastic behaviors of single semiflexible chains with internal
      friction are studied based on the wormlike-chain model. It is shown that the
      frequency dependence of the complex compliance in the high frequency limit is the
      same as that of the Voigt model. This asymptotic behavior appears also for the
      Rouse model with internal friction. We derive the characteristic times for both
      the high frequency limit and the low frequency limit and compare the results with
      those obtained by Khatri et al.

PMID- 20687687
TI  - Reptation of a semiflexible polymer through porous media.
AB  - We study the motion of a single stiff semiflexible filament of length S through
      an array of topological obstacles. By means of scaling arguments and two
      dimensional computer simulations, we show that the stiff chain kinetics follows
      the reptation picture, albeit with kinetic exponents (for the central monomer)
      different from those for flexible chain reptation. At early times when
      topological constraints are irrelevant, the chain kinetics is the anisotropic
      dynamics of a free filament. After the entanglement time tau(e) transverse modes
      are equilibrated under the topological constraints, but the chain is not yet
      correlated over its whole length. During the relaxation of longitudinal modes,
      both the longitudinal fluctuation of the central monomer and the longitudinal
      correlation length grow as approximately sqrt t. After time tau(r) approximately
      S(2) chain ends are correlated, the chain then diffuses globally along the tube
      and tube renewal takes place. In the reptation regime, the longitudinal
      fluctuation of the central monomer grows like approximately t(1). The opening of
      the intermediate approximately sqrt t regime, absent for a free filament, is a
      signature of the reptation process. Although the underlying physics is quite
      different, the intermediate regime is reminiscent of the internal Rouse mode
      relaxation found for reptating flexible chains. In most cases asymptotic power
      laws from scaling could be complemented by prefactors calculated analytically.
      Our results are supported by two-dimensional Langevin simulations with fixed
      obstacles via evaluation of the mean squared displacement of the central monomer.
      The scaling theory can be extended to long semiflexible polymers adopting random
      walk equilibrium configurations and should also apply in three dimensions for
      porous media with pore diameter smaller than the persistence length of the
      filament.

PMID- 20687688
TI  - Defect mediated turbulence in a locally quasiperiodic chemical medium.
AB  - Under a change of conditions, spiral waves in oscillatory reaction-diffusion
      media can become unstable and give rise to a multitude of emergent patterns. For
      example, in bounded domains spiral waves can undergo a resonant Hopf bifurcation
      leading to period-2 spirals which emit wave trains with doubled wavelength and
      temporal period and have a characteristic synchronization defect line. Here, we
      analyze the emergent patterns due to nonresonant Hopf bifurcations in the local
      dynamics giving rise to quasiperiodicity as reported in systems such as the
      peroxidase-oxidase and the Belousov-Zhabotinsky reaction. For a conceptual model
      of the peroxidase-oxidase reaction in a spatially extended medium, we find
      numerically that the additional frequency leads to defect-mediated turbulence.
      This proves that defect-mediated turbulence can indeed exist in media where the
      underlying local dynamics is quasiperiodic. While many statistical features of
      this turbulent dynamics are similar to those observed for other systems, we show
      that there are clear differences if higher-order statistics are considered. In
      particular, we find that the space-time dynamics of the topological defects as
      characterized by the statistics of defect loops is closely related to the
      underlying local dynamics.

PMID- 20687689
TI  - Polymer translocation through alpha-hemolysin pore with tunable polymer-pore
      electrostatic interaction.
AB  - We have measured the ionic current blockages produced by single molecules of
      sodium poly(styrene sulfonate) passing through an alpha-hemolysin protein pore
      under an electric field. Most of the blockage events were composed of one or two
      blockage levels of ionic current. By analyzing the statistics of different event
      types for different polymer lengths, applied voltages, and pH conditions, we have
      identified the molecular mechanism behind the two-level blockages. Our analysis
      of the data shows that not all blockages are successful translocation events and
      the propensity of successful translocation can be tuned by pH gradients across
      the protein pore. We interpret our results as the change in protein-polymer
      interaction via protonation of charged amino acid residues of alpha-hemolysin
      pore. In addition, we have constructed a stochastic theory for polymer
      translocation through alpha-hemolysin pore with tunable polymer-pore
      interactions. The theoretical calculations capture many features observed in our
      experiments.

PMID- 20687690
TI  - Finite-width bundle is most stable in a solution with salt.
AB  - We applied the mean-field approach to a columnar bundle assembled by the parallel
      arrangement of stiff polyelectrolyte rods in a salt bath. The electrostatic
      potential can be divided into two regions: inside the bundle for condensed
      counterions and outside the bundle for free small ions. To determine the
      distribution of condensed counterions inside the bundle, we use a local self
      consistent condition that depends on the charge density, the electrostatic
      potential, and the net polarization. The results showed that, upon bundle
      formation, the electric charge of polyelectrolytes, even those inside the bundle,
      tends to survive in an inhomogeneous manner, and thus their width remains finite
      under thermal equilibrium because of the long-range effect of charge instability.

PMID- 20687691
TI  - Entropic potential field formed for a linear-motor protein near a filament:
      Statistical-mechanical analyses using simple models.
AB  - We report a new progress in elucidating the mechanism of the unidirectional
      movement of a linear-motor protein (e.g., myosin) along a filament (e.g., F
      actin). The basic concept emphasized here is that a potential field is
      entropically formed for the protein on the filament immersed in solvent due to
      the effect of the translational displacement of solvent molecules. The entropic
      potential field is strongly dependent on geometric features of the protein and
      the filament, their overall shapes as well as details of the polyatomic
      structures. The features and the corresponding field are judiciously adjusted by
      the binding of adenosine triphosphate (ATP) to the protein, hydrolysis of ATP
      into adenosine diphosphate (ADP)+Pi, and release of Pi and ADP. As the first
      step, we propose the following physical picture: The potential field formed along
      the filament for the protein without the binding of ATP or ADP+Pi to it is
      largely different from that for the protein with the binding, and the directed
      movement is realized by repeated switches from one of the fields to the other. To
      illustrate the picture, we analyze the spatial distribution of the entropic
      potential between a large solute and a large body using the three-dimensional
      integral equation theory. The solute is modeled as a large hard sphere. Two model
      filaments are considered as the body: model 1 is a set of one-dimensionally
      connected large hard spheres and model 2 is a double helical structure formed by
      two sets of connected large hard spheres. The solute and the filament are
      immersed in small hard spheres forming the solvent. The major findings are as
      follows. The solute is strongly confined within a narrow space in contact with
      the filament. Within the space there are locations with sharply deep local
      potential minima along the filament, and the distance between two adjacent
      locations is equal to the diameter of the large spheres constituting the
      filament. The potential minima form a ringlike domain in model 1 while they form
      a pointlike one in model 2. We then examine the effects of geometric features of
      the solute on the amplitudes and asymmetry of the entropic potential field acting
      on the solute along the filament. A large aspherical solute with a cleft near the
      solute-filament interface, which mimics the myosin motor domain, is considered in
      the examination. Thus, the two fields in our physical picture described above are
      qualitatively reproduced. The factors to be taken into account in further studies
      are also discussed.

PMID- 20687692
TI  - Dominant reaction pathways in protein folding: A direct validation against
      molecular dynamics simulations.
AB  - The dominant reaction pathway (DRP) is an algorithm to microscopically compute
      the most probable reaction pathways in the overdamped Langevin dynamics without
      investing computational time in simulating the local thermal motion in the
      metastable configurations. In order to test the accuracy of such a method, we
      investigate the dynamics of the folding of a beta hairpin within a model that
      accounts for both native and non-native interactions. We compare the most
      probable folding pathways calculated with the DRP method with the folding
      trajectories obtained directly from molecular dynamics simulations. We find that
      the two approaches give consistent results.

PMID- 20687693
TI  - Comment on "Evaluation of surface tension and Tolman length as a function of
      droplet radius from experimental nucleation rate and supersaturation ratio: Metal
      vapor homogeneous nucleation" [J. Chem. Phys. 124, 014506 (2006)].

PMID- 20687695
TI  - Comment on "Ab initio molecular dynamics calculation of ion hydration free
      energies" [J. Chem. Phys. 130, 204507 (2009)].

PMID- 20687699
TI  - Multicomponent wavefield characterization with a novel scanning laser
      interferometer.
AB  - The in-plane component of the wavefield provides valuable information about media
      properties from seismology to nondestructive testing. A new compact scanning
      laser ultrasonic interferometer collects light scattered away from the angle of
      incidence to provide the absolute ultrasonic displacement for both the out-of
      plane and an in-plane components. This new system is tested by measuring the
      radial and vertical polarization of a Rayleigh wave in an aluminum half-space.
      The estimated amplitude ratio of the horizontal and vertical displacement agrees
      well with the theoretical value. The phase difference exhibits a small bias
      between the two components due to a slightly different frequency response between
      the two processing channels of the prototype electronic circuitry.

PMID- 20687700
TI  - Thermoelastic analysis of a silicon surface under x-ray free-electron-laser
      irradiation.
AB  - We present an analysis of the time evolution of a highly excited silicon
      substrate after partial absorption of a femtosecond soft x-ray pulse. The
      detailed time-dependent thermoelastic behavior of the substrate in terms of the
      displacements u(r,t) is derived for time delays for which the usual local
      thermodynamic variables, temperature T(r,t) and density n(r,t), become well
      defined, namely, a few hundred femtoseconds after x-ray pulse absorption. For
      practical optical components under present conditions of operation with trains of
      pulses, we find that in a worst case scenario, already the 50th pulse in the
      train could be adversely affected by dynamic distortion induced by the preceding
      pulses [corrected]

PMID- 20687701
TI  - Stoichiometric analysis of compositionally graded combinatorial amorphous thin
      film oxides using laser-induced breakdown spectroscopy.
AB  - Laser-induced breakdown spectroscopy (LIBS) is a recently developed locally
      destructive elemental analysis technique that can be used to analyze solid,
      liquid, and gaseous samples. In the system explored here, a neodymium-doped
      yttrium aluminum garnet laser ablates a small amount of the sample and spectral
      emission from the plume is analyzed using a set of synchronized spectrometers. We
      explore the use of LIBS to map the stoichiometry of compositionally graded
      amorphous indium zinc oxide thin-film libraries. After optimization of the
      experimental parameters (distance between lens and samples, spot size on the
      samples, etc.), the LIBS system was calibrated against inductively coupled plasma
      atomic emission spectroscopy which resulted in a very consistent LIBS-based
      elemental analysis. Various parameters that need to be watched closely in order
      to produce consistent results are discussed. We also compare LIBS and x-ray
      fluorescence as techniques for the compositional mapping of libraries.

PMID- 20687702
TI  - A simple, compact, and efficient diode-side-pumped linear intracavity frequency
      doubled Nd:YAG rod laser with 50 ns pulse width and 124 W green output power.
AB  - We have developed an efficient and high power repetitively Q-switched diode
      pumped intracavity frequency doubled Nd:YAG/LiB(3)O(5) based green laser capable
      of generating 124 W of average green power with 50 ns pulse duration in a highly
      compact and robust linear cavity configuration. The pump to green beam conversion
      efficiency is 16.8% and the overall wall-plug efficiency is 8.3%. The long term
      power stability is excellent with +/-0.4 W variation at the maximum output power
      and +/-2% amplitude fluctuation with +/-2.9 ns timing jitter. The M(2) parameter
      of the green beam was measured to be approximately 27. This, combined with the
      short pulse duration and the high average power, makes this laser ideal for
      pumping ultrafast Ti:sapphire laser amplifier systems and for micromachining
      applications.

PMID- 20687704
TI  - Short vertical tube furnace for the fabrication of doped glass microsphere
      lasers.
AB  - We report on the design of an electric tube furnace that can be used for the
      fabrication of doped glass microsphere lasers. The tube furnace has a short hot
      zone of length 133 mm and is based on a quartz tube design. Doped laser glass
      particles, specifically Er:Yb phosphate glass (IOG-2), of approximately 1 microm
      diameter are blown into the furnace using a 60 ml syringe and microspheres
      ranging in size from 10 to 400 microm are collected at the output of the tube
      furnace in a Petri dish. The furnace operates at a wall temperature of
      approximately 900 degrees C and is capable of making microspheres from glasses
      with glass transition temperatures of at least 375 degrees C. High quality (Q
      approximately 10(5)) whispering gallery modes have been excited within the
      microspheres by optically pumping at 978 nm via a tapered optical fiber.

PMID- 20687703
TI  - Wideband and high-gain frequency stabilization of a 100-W injection-locked Nd:YAG
      laser for second-generation gravitational wave detectors.
AB  - Second-generation gravitational wave detectors require a highly stable laser with
      an output power greater than 100 W to attain their target sensitivity. We have
      developed a frequency stabilization system for a 100-W injection-locked Nd:YAG
      (yttrium aluminum garnet) laser. By placing an external wideband electro-optic
      modulator used as a fast-frequency actuator in the optical path of the slave
      output, we can circumvent a phase delay in the frequency control loop originating
      from the pole of an injection-locked slave cavity. Thus, we have developed an
      electro-optic modulator made of a MgO-doped stoichiometric LiNbO(3) crystal.
      Using this modulator, we achieve a frequency control bandwidth of 800 kHz and a
      control gain of 180 dB at 1 kHz. These values satisfy the requirement for a laser
      frequency control loop in second-generation gravitational wave detectors.

PMID- 20687705
TI  - A new tandem mass spectrometer for photofragment spectroscopy of cold, gas-phase
      molecular ions.
AB  - We present here the design of a new tandem mass spectrometer that combines an
      electrospray ion source with a cryogenically cooled ion trap for spectroscopic
      studies of cold, gas-phase ions. The ability to generate large ions in the gas
      phase without fragmentation, cool them to approximately 10 K in an ion trap, and
      perform photofragment spectroscopy opens up new possibilities for spectroscopic
      characterization of large biomolecular ions. The incorporation of an ion funnel,
      together with a number of small enhancements, significantly improves the
      sensitivity, signal stability, and ease of use compared with the previous
      instrument built in our laboratory.

PMID- 20687706
TI  - Tunable ultrafast extreme ultraviolet source for time- and angle-resolved
      photoemission spectroscopy.
AB  - We present a laser-based apparatus suitable for visible pump/extreme UV (XUV)
      probe time-, energy-, and angle-resolved photoemission spectroscopy utilizing
      high-harmonic generation from a noble gas. Tunability in a wide range of energies
      (currently 20-36 eV) is achieved by using a time-delay compensated monochromator,
      which also preserves the ultrashort duration of the XUV pulses. Using an
      amplified laser system at 10 kHz repetition rate, approximately 10(9)-10(10)
      photons/s per harmonic are made available for photoelectron spectroscopy.
      Parallel energy and momentum detection is carried out in a hemispherical electron
      analyzer coupled with an imaging detector. First applications demonstrate the
      capabilities of the instrument to easily select the probe wavelength of choice,
      to obtain angle-resolved photoemission maps (GaAs and URu(2)Si(2)), and to trace
      ultrafast electron dynamics in an optically excited semiconductor (Ge).

PMID- 20687707
TI  - A new flexible monochromator setup for quick scanning x-ray absorption
      spectroscopy.
AB  - A new monochromator setup for quick scanning x-ray absorption spectroscopy in the
      subsecond time regime is presented. Novel driving mechanics allow changing the
      energy range of the acquired spectra by remote control during data acquisition
      for the first time, thus dramatically increasing the flexibility and convenience
      of this method. Completely new experiments are feasible due to the fact that time
      resolution, edge energy, and energy range of the acquired spectra can be changed
      continuously within seconds without breaking the vacuum of the monochromator
      vessel and even without interrupting the measurements. The advanced mechanics are
      explained in detail and the performance is characterized with x-ray absorption
      spectra of pure metal foils. The energy scale was determined by a fast and
      accurate angular encoder system measuring the Bragg angle of the monochromator
      crystal with subarcsecond resolution. The Bragg angle range covered by the
      oscillating crystal can currently be changed from 0 degrees to 3.0 degrees within
      20 s, while the mechanics are capable to move with frequencies of up to ca. 35
      Hz, leading to ca. 14 ms/spectrum time resolution. A new software package allows
      performing programmed scan sequences, which enable the user to measure stepwise
      with alternating parameters in predefined time segments. Thus, e.g., switching
      between edges scanned with the same energy range is possible within one in situ
      experiment, while also the time resolution can be varied simultaneously. This
      progress makes the new system extremely user friendly and efficient to use for
      time resolved x-ray absorption spectroscopy at synchrotron radiation beamlines.

PMID- 20687708
TI  - Axicon based conical resonators with high power copper vapor laser.
AB  - We report for the first time the performance of axicon based conical resonators
      (ABCRs) in a copper vapor laser, with novel results. The unstable conical
      resonator comprising of conical mirror (reflecting axicon) with axicon angle
      approximately pi/18, cone angle approximately 160 degrees, and a convex mirror of
      60 cm radius of curvature was effective in reducing the average beam divergence
      to approximately 0.15 mrad (approximately 25 fold reduction compared to standard
      multimode plane-plane cavity) with output power of approximately 31 W. Extraction
      efficiency of approximately 50%-60% and beam divergence of <1 mrad was achieved
      in other stable ABCR configurations using flat and concave mirrors with the
      axicon. This is a significant improvement compared to 4-5 mrad normally observed
      in conventional stable resonators in copper vapor lasers. The conical resonators
      with copper vapor laser provide high misalignment tolerance beta approximately 4
      5 mrad where beta is the tilt angle of the conical mirror from optimum position
      responsible for approximately 20% decline in laser power. The depth of focus d
      was approximately three times larger in case of conical resonator as compared to
      that of standard spherical unstable resonator under similar beam divergence and
      focusing conditions.

PMID- 20687709
TI  - Kilohertz dye laser system for high resolution laser spectroscopy.
AB  - We have electro-optically sliced the output light of a commercial Coherent
      Evolution Nd:YLF laser to pump a kilohertz repetition rate nanosecond dye laser
      system. Simple and highly adjustable, this laser system can easily be used for
      initial state preparation for ultrafast systems as well as high resolution
      spectroscopy.

PMID- 20687710
TI  - Determining time resolution of microchannel plate detectors for electron time-of
      flight spectrometers.
AB  - The temporal resolution of a 40 mm diameter chevron microchannel plate (MCP)
      detector followed by a constant fraction discriminator and a time-to-digital
      converter was determined by using the third order harmonic of 25 fs Ti:sapphire
      laser pulses. The resolution was found to deteriorate from 200 to 300 ps as the
      total voltage applied on the two MCPs increased from 1600 to 2000 V. This was
      likely due to a partial saturation of the MCP and/or the constant fraction
      discriminator working with signals beyond its optimum range of pulse width and
      shape.

PMID- 20687711
TI  - Design and construction of pulsed neutron diagnostic system for plasma focus
      device (SBUPF1).
AB  - In this paper, two designs of pulsed neutron counter structure are introduced. To
      increase the activation counter efficiency, BC-400 plastic scintillator plates
      along with silver foils are utilized. Rectangular cubic and cylindrical
      geometries for activation counter cell are modeled using MCNP4C code. Eventually,
      an optimum length of 14 cm is calculated for the detector cell and optimum
      numbers of 20 silver foils for rectangular cubic geometry and ten foils for
      cylindrical geometry have been acquired. Due to the high cost of cutting,
      polishing of plastics, and etc., the rectangular cubic design is found to be more
      economical than the other design. In order to examine the functionality and
      ensure the detector output and corresponding designing, neutron yield of a 2.48
      kJ plasma focus device (SBUPF1) in 8 mbar pressure with removal source method for
      calibration was measured (3.71+/-0.32)x10(7) neutrons per shot.

PMID- 20687712
TI  - An open-walled ionization chamber appropriate to tritium monitoring for glovebox.
AB  - An open-walled ionization chamber is developed to monitor the tritium
      concentration in gloveboxes in tritium processing systems. Two open walls are
      used to replace the sealed wall in common ionization chambers, through which the
      tritium gas can diffuse into the chamber without the aid of pumps and pipelines.
      Some basic properties of the chamber are examined to evaluate its performance.
      Results turn out that an open-walled chamber of 1 l in volume shows a
      considerably flat plateau over 700 V for a range of tritium concentration. The
      chamber also gives a good linear response to gamma fields over 4 decades under a
      pressure condition of 1 atm. The pressure dependence characteristics show that
      the ionization current is only sensitive at low pressures. The pressure influence
      becomes weaker as the pressure increases mainly due to the decrease in the mean
      free path of beta particles produced by tritium decay. The minimum detection
      limit of the chamber is 3.7x10(5) Bq/m(3).

PMID- 20687713
TI  - Spatially uniform calibration of a liquid xenon detector at low energies using
      (83m)Kr.
AB  - A difficult task with many particle detectors focusing on interactions below
      approximately 100 keV is to perform a calibration in the appropriate energy range
      that adequately probes all regions of the detector. Because detector response can
      vary greatly in various locations within the device, a spatially uniform
      calibration is important. We present a new method for calibration of liquid xenon
      (LXe) detectors, using the short-lived (83m)Kr. This source has transitions at
      9.4 and 32.1 keV, and as a noble gas like Xe, it disperses uniformly in all
      regions of the detector. Even for low source activities, the existence of the two
      transitions provides a method of identifying the decays that is free of
      background. We find that at decreasing energies, the LXe light yield increases,
      while the amount of electric field quenching is diminished. Additionally, we show
      that if any long-lived radioactive backgrounds are introduced by this method,
      they will present less than 67x10(-6) events kg(-1) day(-1) keV(-1) in the next
      generation of LXe dark matter direct detection searches.

PMID- 20687714
TI  - A high resolution, broad energy acceptance spectrometer for laser wakefield
      acceleration experiments.
AB  - Laser wakefield experiments present a unique challenge in measuring the resulting
      electron energy properties due to the large energy range of interest, typically
      several 100 MeV, and the large electron beam divergence and pointing jitter >1
      mrad. In many experiments the energy resolution and accuracy are limited by the
      convolved transverse spot size and pointing jitter of the beam. In this paper we
      present an electron energy spectrometer consisting of two magnets designed
      specifically for laser wakefield experiments. In the primary magnet the field is
      produced by permanent magnets. A second optional electromagnet can be used to
      obtain better resolution for electron energies above 75 MeV. The spectrometer has
      an acceptance of 2.5-400 MeV (E(max)/E(min)>100) with a resolution of better than
      1% rms for electron energies above 25 MeV. This high resolution is achieved by
      refocusing electrons in the energy plane and without any postprocessing image
      deconvolution. Finally, the spectrometer employs two complimentary detection
      mechanisms: (1) absolutely calibrated scintillation screens imaged by cameras
      outside the vacuum chamber and (2) an array of scintillating fibers coupled to a
      low-noise charge-coupled device.

PMID- 20687715
TI  - A system for measuring bubble voidage and frequency around tubes immersed in a
      fluidized bed of particles.
AB  - Gas-solid fluidized beds are common in chemical processing and energy production
      industries. These types of reactors frequently have banks of tubes immersed
      within the bed to provide heating or cooling, and it is important that the fluid
      dynamics within these bundles is efficient and uniform. This paper presents a
      simple, low-cost method for quantitatively analyzing the behavior of gas bubbles
      within banks of tubes in a fluidized bed cold flow model. Two probes, one
      containing an infrared emitter and one containing an infrared (IR) detector, are
      placed into adjacent glass tubes such that the emitter and detector face each
      other. As bubbles pass through the IR beam, the detector signal increases due to
      less solid material blocking the path between the emitter and detector. By
      calibrating the signal response to known voidage of the material, one can measure
      the bubble voidage at various locations within the tube bundle. The rate and size
      of bubbles passing through the beam can also be determined by high frequency data
      collection and subsequent analysis. This technique allows one to develop a map of
      bubble voidage within a fluidized bed, which can be useful for model validation
      and system optimization.

PMID- 20687716
TI  - A new all-digital time differential gamma-gamma angular correlation spectrometer.
AB  - A new digital time differential perturbed angular correlation spectrometer,
      designed to measure the energy of and coincidence time between correlated
      detector signals, here correlated gamma photons, is presented. The system
      overcomes limitations of earlier digital approaches and features improved
      performance and handling. By consequently separating the data recording and
      evaluation, it permits the simultaneous measurement of decays with several gamma
      ray cascades at once and avoids the necessity of premeasurement configuration.
      Tests showed that the spectrometer reaches a time resolution of 460 ps [using a
      (60)Co sample and Lu(1.8)Y(0.2)SiO(5):Ce (LYSO) scintillators, otherwise better
      than 100 ps], an energy resolution that is equivalent to the limit of the used
      scintillation material, and a processing capability of more than 200,000 gamma
      quanta per detector and second. Other possible applications of the presented
      methods include nuclear spectroscopy, positron emission tomography, time of
      flight studies, lidar, and radar.

PMID- 20687717
TI  - Tangential soft-x ray imaging for three-dimensional structural studies in a
      reversed field pinch.
AB  - Tangential soft-x ray (SXR) imaging diagnostic has been developed and three
      dimensional (3D) structure of the internal magnetic surface has been deduced by
      comparing the experimental and calculated two-dimensional SXR images in a
      reversed field pinch. The SXR imaging system, consisting of a MCP, a fluorescent
      plate, and an intensified charge coupled device camera, has been installed in
      REversed field pinch of Low-Aspect-ratio eXperiment (RELAX) machine. Major
      characteristics of an experimental SXR image could be reproduced by numerical
      calculations of the image using a single island model, suggesting a helical hot
      core in RELAX. The SXR imaging system could be useful for 3D structural studies
      when tangential and vertical simultaneous imaging systems would be installed,
      with appropriate numerical modeling of 3D structure of the magnetic surfaces.

PMID- 20687718
TI  - High-speed dual Langmuir probe.
AB  - In an effort to temporally resolve the electron density, electron temperature,
      and plasma potential for turbulent plasma discharges, a unique high-speed dual
      Langmuir probe (HDLP) has been developed. A traditional single Langmuir probe of
      cylindrical geometry (exposed to the plasma) is swept simultaneously with a
      nearby capacitance and noise compensating null probe (fully insulated from the
      plasma) to enable bias sweep rates on a microsecond timescale. Traditional thin
      sheath Langmuir probe theory is applied for interpretation of the collected probe
      data. Data at a sweep rate of 100 kHz are presented; however the developed system
      is capable of running at 1 MHz-near the upper limit of the applied electrostatic
      Langmuir probe theory for the investigated plasma conditions. Large sets (100,000
      sweeps at each of 352 spatial locations) of contiguous turbulent plasma
      properties are collected using simple electronics for probe bias driving and
      current measurement attaining 80 dB signal-to-noise measurements with dc to 1 MHz
      bandwidth. Near- and far-field plume measurements with the HDLP system are
      performed downstream from a modern Hall effect thruster where the time-averaged
      plasma properties exhibit the approximate ranges: electron density n(e) from
      (1x10(15))-(5x10(16)) m(-3), electron temperature T(e) from 1 to 3.5 eV, and
      plasma potential V(p) from 5 to 15 V. The thruster discharge of 200 V (constant
      anode potential) and 2 A (average discharge current) displays strong, 2.2 A peak
      to-peak, current oscillations at 19 kHz, characteristic of the thruster
      "breathing mode" ionization instability. Large amplitude discharge current
      fluctuations are typical for most Hall thrusters, yet the HDLP system reveals the
      presence of the same 19 kHz fluctuations in n(e)(t), T(e)(t), and V(p)(t)
      throughout the entire plume with peak-to-peak divided by mean plasma properties
      that average 94%. The propagation delays between the discharge current
      fluctuations and the corresponding plasma density fluctuations agree well with
      expected ion transit-times observed with distinct plasma waves traveling away
      from the thruster at velocities >10 km/s.

PMID- 20687719
TI  - A novel flat-response x-ray detector in the photon energy range of 0.1-4 keV.
AB  - A novel flat-response x-ray detector has been developed for the measurement of
      radiation flux from a hohlraum. In order to obtain a flat response in the photon
      energy range of 0.1-4 keV, it is found that both the cathode and the filter of
      the detector can be made of gold. A further improvement on the compound filter
      can then largely relax the requirement of the calibration x-ray beam. The
      calibration of the detector, which is carried out on Beijing Synchrotron
      Radiation Facility at Institute of High Energy Physics, shows that the detector
      has a desired flat response in the photon energy range of 0.1-4 keV, with a
      response flatness smaller than 13%. The detector has been successfully applied in
      the hohlraum experiment on Shenguang-III prototype laser facility. The radiation
      temperatures inferred from the detector agree well with those from the diagnostic
      instrument Dante installed at the same azimuth angle from the hohlraum axis,
      demonstrating the feasibility of the detector.

PMID- 20687720
TI  - A uniformly redundant imaging array of penumbral apertures coupled with a
      heuristic reconstruction for hard x-ray and neutron imaging.
AB  - A coded imaging and decoding (image reconstruction) scheme was developed for
      diagnosing a hot and dense region emitting hard x-rays and neutrons in laser
      fusion plasmas. Because the imager was a uniformly redundant array of penumbral
      aperture (URPA) arranged in an M-matrix, URPA leads to N times (N: the total
      number of apertures) enhancement of signal intensity in comparison with a single
      penumbral aperture. A recorded penumbral image was reconstructed by a computer
      based heuristic method to reduce artifacts caused by noises contained in a
      penumbral image. Applicability of this technique was investigated by imaging x
      rays emitted from laser-produced plasmas, demonstrating a spatial resolution of
      16 microm. Under the present conditions, the spatial resolution was determined
      dominantly by a detector resolution (10.5 microm) and a signal-to-noise ratio of
      the obtained penumbral image.

PMID- 20687721
TI  - Electron cyclotron emission reconstruction image and m/n = 3/2 mode in HT-7
      tokamak.
AB  - Electron cyclotron emission reconstruction image has been used for flux surface
      reconstruction. The reconstruction image is based on plasma rigid rotation which
      is obtained from Mirnov diagnostic. From the reconstructed two-dimensional flux
      surface, the classical m/n = 3/2 mode is visualized, which is of similar spatial
      structure as neoclassical 3/2 mode observed in some other tokamaks [B. Esposito
      et al., Phys. Rev. Lett. 100, 045006 (2008)].

PMID- 20687722
TI  - The MaPLE device of Saha Institute of Nuclear Physics: construction and its
      plasma aspects.
AB  - The Magnetized Plasma Linear Experimental (MaPLE) device is a low cost laboratory
      plasma device at Saha Institute of Nuclear Physics fabricated in-house with the
      primary aim of studying basic plasma physics phenomena such as plasma
      instabilities, wave propagation, and their nonlinear behavior in magnetized
      plasma regime in a controlled manner. The machine is specially designed to be a
      versatile laboratory device that can provide a number of magnetic and electric
      scenario to facilitate such studies. A total of 36 number of 20-turn magnet
      coils, designed such as to allow easy handling, is capable of producing a
      uniform, dc magnetic field of about 0.35 T inside the plasma chamber of diameter
      0.30 m. Support structure of the coils is planned in an innovative way
      facilitating straightforward fabrication and easy positioning of the coils.
      Further special feature lies in the arrangement of the spacers between the coils
      that can be maneuvered rather easily to create different magnetic configurations.
      Various methods of plasma production can be suitably utilized according to the
      experimental needs at either end of the vacuum vessel. In the present paper,
      characteristics of a steady state plasma generated by electron cyclotron
      resonance method using 2.45 GHz microwave power are presented. Scans using simple
      probe drives revealed that a uniform and long plasma column having electron
      density approximately 3-5x10(10) cm(-3) and temperature approximately 7-10 eV, is
      formed in the center of the plasma chamber which is suitable for wave launching
      experiments.

PMID- 20687723
TI  - Quantum-dot-array diffraction grating with single order diffraction property for
      soft x-ray region.
AB  - A gold transmission grating is used routinely to disperse the x-ray spectrum at
      the Z soft x-ray facility to measure the spectrum and temporal history of the
      absolute soft x-ray power emitted from z-pinch and hohlraum radiation sources. A
      quantum-dot-array diffraction grating (QDADG) of 250 lines/mm for soft x-ray is
      designed and fabricated for the first time according to the principle of binary
      sinusoidal transmission grating. The diffraction efficiencies of the grating are
      measured in the 150-300 eV photon energy range on the Beamline 3W1B of Beijing
      Synchrotron Radiation Facility. This article describes the basic concept and
      calibration techniques and presents calibration results. It is shown that the 250
      lines/mm QDADG can be used to disperse light without higher-order diffractions in
      soft x-ray range, and the diffraction efficiencies of this grating are nearly
      constant (about 25%), which is beneficial in the spectrum analysis.

PMID- 20687724
TI  - A new absolute extreme ultraviolet image system designed for studying the
      radiated power of the Joint Texas Experimental Tokamak discharges.
AB  - A bolometer imaging system mounted on different toroidal and poloidal locations
      used for radiation observation has been developed in the Joint Texas Experimental
      Tokamak (J-TEXT tokamak). Three miniature pinhole AXUV16ELG (16 elements absolute
      extreme ultraviolet silicon photodiodes) array cameras, which are settled down in
      the same toroidal position but in three different poloidal places, can provide a
      broad viewing angle that covers the whole plasma cross-section, and hence can
      measure the total radiated power and provide the radiated emissive profile, while
      nine AXUV10EL (10 elements absolute extreme ultraviolet silicon photodiodes)
      array cameras are divided into three groups and will be mounted on different
      toroidal locations to observe the toroidal radiated power distribution. Among
      these detectors, one element of the AXUV16ELG array is absolutely calibrated by
      the synchrotron radiation source to verify the system reliability. Although there
      are some discrepancies between the typical responsivity given by IRD Co. and the
      calibrated results, it is confirmed that the discrepancies have no major effect
      on the final result after the simulation. The details of the system as well as
      observations are presented in the paper.

PMID- 20687725
TI  - Thermal exchange radius measurement: application to nanowire thermal imaging.
AB  - In scanning thermal microscopy (SThM) techniques, the thermal exchange radius
      between tip and sample is a crucial parameter. Indeed, it limits the lateral
      spatial resolution but, in addition, an accurate value of this parameter is
      necessary for a precise identification of thermal properties. But until now, the
      thermal exchange radius is usually estimated but not measured. This paper
      presents an experimental procedure, based on the 3omega-SThM method, to measure
      its value. We apply this procedure to evaluate the thermal exchange radius of two
      commercial probes: the well-known Wollaston one and a new probe constituted of a
      palladium film on a SiO(2) substrate. Finally, presenting silicon nanowire
      images, we clearly demonstrate that this new probe can reach a spatial resolution
      better than 100 nm whereas the Wollaston probe hardly reaches a submicronic
      spatial resolution.

PMID- 20687726
TI  - A simple hard x-ray "nanoslit" for measuring wavefront intensity.
AB  - A new method is proposed for nanoscale hard x-ray measurements. This method uses
      a reflection on a heavy-metal wire that functions as a single slit with a
      nanoscale aperture for a parallel x-ray beam. This "nanoslit" can be used to
      perform high-spatial-resolution measurements of the intensity distribution of a
      wavefront that diverges from an aperture. In experiments, Fresnel fringes
      generated by a rectangular aperture were measured using a 300-microm-diameter
      platinum wire as the nanoslit. In these experiments, the finest fringes with a
      period of 26 nm could be successfully resolved.

PMID- 20687727
TI  - Quality analysis of selective microparticle deposition on electrically
      programmable surfaces.
AB  - Image processing and pattern analysis can evaluate the deposition quality of
      triboelectrically charged microparticles on charged surfaces. The image
      processing method presented in this paper aims at controlling the quality of
      peptide arrays generated by particle based solid phase Merrifield combinatorial
      peptide synthesis. Incorrectly deposited particles are detected before the amino
      acids therein are coupled to the growing peptide. The calibration of the image
      acquisition is performed in a supervised training step in which all parameters of
      the quality analyzing algorithm are learnt given one representative image. Then,
      the correct deposition pattern is determined by a linear support vector machine.
      Knowing the pattern, contaminated areas can be detected by comparing the pattern
      with the actual deposition. Taking into account the resolution of the image
      acquisition system and its magnification factor, the number and size of
      contaminating particles can be calculated out of the number of connected
      foreground pixels.

PMID- 20687728
TI  - Digitally tunable, wide-band amplitude, phase, and frequency detection for atomic
      resolution scanning force microscopy.
AB  - Frequency-modulation atomic force microscopy (FM-AFM) relies on an accurate
      tracking of the resonance frequency of a scanning probe. It is now used in
      environments ranging from ultrahigh vacuum to aqueous solutions, for slow and for
      fast imaging, with probes resonating from a few kilohertz up to several
      megahertz. Here we present a versatile experimental setup that detects amplitude,
      phase, and frequency of AFM probes for resonance frequencies up to 15 MHz and
      with >70 kHz maximum bandwidth for amplitude/phase detection. We provide generic
      parameter settings for variable-bandwidth frequency detection and test these
      using our setup. The signal-to-noise ratio of the frequency detector is
      sufficiently high to record atomic-resolution images of mica by FM-AFM in aqueous
      solution.

PMID- 20687729
TI  - Self-manifestation and universal correction of image distortion in scanning
      tunneling microscopy with spiral scan.
AB  - We demonstrate that severe distortions may occur but hard to identify in a
      standard line-by-line scanned scanning tunneling microscope image, deforming the
      atomic lattice into a completely different structure type and leading to a wrong
      interpretation of the data. We also show that a spiral scan image can reveal the
      details of the drifting by causing the atomic rows to bend with the curvatures
      being closely related to the extent and direction of the drifting. By
      straightening the curved atomic rows, the true atomic arrangement can thus be
      precisely recovered.

PMID- 20687730
TI  - Multiple-scanning-probe tunneling microscope with nanoscale positional
      recognition function.
AB  - Over the past decade, multiple-scanning-probe microscope systems with
      independently controlled probes have been developed for nanoscale electrical
      measurements. We developed a quadruple-scanning-probe tunneling microscope
      (QSPTM) that can determine and control the probe position through scanning-probe
      imaging. The difficulty of operating multiple probes with submicrometer precision
      drastically increases with the number of probes. To solve problems such as
      determining the relative positions of the probes and avoiding of contact between
      the probes, we adopted sample-scanning methods to obtain four images
      simultaneously and developed an original control system for QSPTM operation with
      a function of automatic positional recognition. These improvements make the QSPTM
      a more practical and useful instrument since four images can now be reliably
      produced, and consequently the positioning of the four probes becomes easier
      owing to the reduced chance of accidental contact between the probes.

PMID- 20687731
TI  - Intermittent contact hydration scanning probe microscopy.
AB  - Hydration scanning probe microscopy is a technique similar to scanning tunneling
      microscopy, in which the probe current, sustained by the slight surface
      conduction of a thin hydration layer covering an insulating support surface, is
      essentially electrochemical in nature instead of electronic tunneling. Such a
      technique allows the imaging of a great variety of samples, including insulators,
      provided that they are hydrophilic, as well as the study of molecular samples of
      biological interest (such as DNA) fixed on a suitable supporting surface. The
      main problem to obtain stable and reproducible images comes from the very
      critical determination of the operating conditions under which the probe
      hydration layer interaction does not lead to the formation of a relatively large
      water meniscus. It has been suggested that this issue can be removed by adding a
      high frequency oscillation to the probe movement, as in tapping atomic force
      microscopy. Meniscus formation and breakup have been investigated in order to
      determine the best values for the amplitude and the frequency of the oscillation.
      Results obtained in this mode are discussed in comparison with the usual
      continuous contact mode.

PMID- 20687732
TI  - Real-time optical system for observing crystallization in levitated silicate melt
      droplets.
AB  - In this study, a real-time optical system was developed to observe
      crystallization in a small spherical melt droplet (few millimeters in diameter)
      by containerless processing. This system can be used to simultaneously observe
      the inside and the surface of a transparent melt droplet, as well as its ambient
      gas atmosphere at high temperatures. A silicate melt with a diameter of
      approximately 2 mm and a composition of MgO:SiO(2)=48:52 was levitated using a
      gas-jet levitation system, and its crystallization process was successfully
      observed from 2385 K in real time with good contrast using the developed optical
      setup.

PMID- 20687733
TI  - Noise analysis of grating-based x-ray differential phase contrast imaging.
AB  - The sensitivity of x-ray radiographic images, meaning the minimal detectable
      change in the thickness or in the index of refraction of a sample, is directly
      related to the uncertainty of the measurement method. In the following work, we
      report on the recent development of quantitative descriptions for the stochastic
      error of grating-based differential phase contrast imaging (DPCi). Our model
      includes the noise transfer characteristics of the x-ray detector and the jitter
      of the phase steps. We find that the noise in DPCi depends strongly on the phase
      stepping visibility and the sample properties. The results are supported by
      experimental evidence acquired with our new instrument with a field of view of
      50x70 mm(2). Our conclusions provide general guidelines to optimize grating
      interferometers for specific applications and problems.

PMID- 20687734
TI  - Fabrication of multilayer Laue lenses by a combination of pulsed laser deposition
      and focused ion beam.
AB  - X-ray diffractive techniques using Fresnel zone plate lenses of various forms are
      of great technical interest because of their ability to form images at very high
      spatial resolution, but the zone plates are unfortunately very hard to produce by
      lithography. Alternatively, multilayer Laue lenses (MLLs) and multilayer zone
      plates are used due to the higher and easily adjustable aspect ratio necessary
      for different wavelengths. In this paper, the fabrication of a MLL by a
      combination of pulsed laser deposition and focused ion beam machining is
      described. All steps of the production of a Ti/ZrO(2) microlens test structure
      with focal length of 220 microm (for a wavelength of 2.88 nm in the "water
      window" regime) are explained in detail. It is shown that this combination of two
      powerful techniques is very effective for the fabrication of MLL. All steps can
      be done in a very precise and controlled way without introducing damage to the
      grown multilayer structures.

PMID- 20687735
TI  - An alternative method to determining optical lever sensitivity in atomic force
      microscopy without tip-sample contact.
AB  - Force studies using atomic force microscopy generally require knowledge of the
      cantilever spring constants and the optical lever sensitivity. The traditional
      method of evaluating the optical lever sensitivity by pressing the tip against a
      hard surface can damage the tip, especially sharp ones. Here a method is shown to
      calculate the sensitivity without having to bring the tip into contact. Instead a
      sharpened tungsten wire is used to cause a point contact directly onto the
      cantilever and cause cantilever bending. Using beam theory, the sensitivity thus
      found can be converted to the equivalent sensitivity that would be obtained using
      the tip location. A comparison is presented between sensitivity values obtained
      from the conventional tip contact method and those derived from the wire-based
      technique for a range of cantilevers in air. It was found that the difference
      between the calculated sensitivity from the wire-based technique and the
      sensitivity obtained conventionally was less than 12%. These measurements
      indicate the presented method offers a simple alternative approach to obtain
      optical lever sensitivity without compromising the tip shape.

PMID- 20687736
TI  - Hot nanoindentation in inert environments.
AB  - An instrument capable of performing nanoindentation at temperatures up to 500
      degrees C in inert atmospheres, including partial vacuum and gas near atmospheric
      pressures, is described. Technical issues associated with the technique (such as
      drift and noise) and the instrument (such as tip erosion and radiative heating of
      the transducer) are identified and addressed. Based on these considerations,
      preferred operation conditions are identified for testing on various materials.
      As a proof-of-concept demonstration, the hardness and elastic modulus of three
      materials are measured: fused silica (nonoxidizing), aluminum, and copper (both
      oxidizing). In all cases, the properties match reasonably well with published
      data acquired by more conventional test methods.

PMID- 20687737
TI  - Wide-range wavevector selectivity of magnon gases in Brillouin light scattering
      spectroscopy.
AB  - Brillouin light scattering spectroscopy is a powerful technique for the study of
      fast magnetization dynamics with both frequency and wavevector resolutions. Here,
      we report on a distinct improvement of this spectroscopic technique toward two
      dimensional wide-range wavevector selectivity in a backward scattering geometry.
      Spin-wave wavevectors oriented perpendicularly to the bias magnetic field are
      investigated by tilting the sample within the magnet gap. Wavevectors which are
      oriented parallel to the applied magnetic field are analyzed by turning the
      entire setup, including the magnet system. The setup features a wide selectivity
      of wavevectors up to 2.04x10(5) rad/cm for both orientations, and allows
      selecting and measuring wavevectors of dipole- and exchange-dominated spin waves
      of any orientation to the magnetization simultaneously.

PMID- 20687738
TI  - Simplified manual fabrication of cubic-zirconia gem anvils for extended energy
      range spectroscopic studies to routine high pressures of 100-150 kbar (10-15
      GPa).
AB  - Methodology has been developed so as to attain routine extreme conditions as high
      as 10-15 GPa in a gem anvil optical pressure cell using hand (manual) processed
      gem anvils. The anvils polished by a simplified hand held tool are inexpensive
      single crystal cubic zirconia (CZ) gems that have various optical advantages over
      diamond anvils. Appreciable pressures are attained with culet and corresponding
      sample cavity dimensions that are relatively convenient to load with sample
      material. Some technical details are provided as regards the simplified manual
      fabrication process, thus emphasizing the relative ease and cost effectiveness of
      the hand polishing technique for fabricating such high pressure anvils. Raman
      spectroscopy measurements, in triple subtractive mode with a confocal pinhole
      geometry, are used to exemplify the usefulness of the CZ gem anvil cell
      methodology in pressure tuning experiments. This is particularly convenient for
      conventional low wave-number (lattice mode regime) Raman high pressure studies,
      which have not been reported previously in this context. Various other
      applications of such anvils are suggested.

PMID- 20687739
TI  - RASOR: an advanced instrument for soft x-ray reflectivity and diffraction.
AB  - We report the design and construction of a novel soft x-ray diffractometer
      installed at Diamond Light Source. The beamline endstation RASOR is constructed
      for general users and designed primarily for the study of single crystal
      diffraction and thin film reflectivity. The instrument is comprised of a limited
      three circle (theta, 2theta, and chi) diffractometer with an additional removable
      rotation (phi) stage. It is equipped with a liquid helium cryostat, and post
      scatter polarization analysis. Motorized motions are provided for the precise
      positioning of the sample onto the diffractometer center of rotation, and for
      positioning the center of rotation onto the x-ray beam. The functions of the
      instrument have been tested at Diamond Light Source, and initial test
      measurements are provided, demonstrating the potential of the instrument.

PMID- 20687740
TI  - Turnbuckle diamond anvil cell for high-pressure measurements in a superconducting
      quantum interference device magnetometer.
AB  - We have developed a miniature diamond anvil cell for magnetization measurements
      in a widely used magnetic property measurement system commercial magnetometer
      built around a superconducting quantum interference device. The design of the
      pressure cell is based on the turnbuckle principle in which force can be created
      and maintained by rotating the body of the device while restricting the
      counterthreaded end-nuts to translational movement. The load on the opposed
      diamond anvils and the sample between them is generated using a hydraulic press.
      The load is then locked by rotating the body of the cell with respect to the end
      nuts. The dimensions of the pressure cell have been optimized by use of finite
      element analysis. The cell is approximately a cylinder 7 mm long and 7 mm in
      diameter and weighs only 1.5 g. Due to its small size the cell thermalizes
      rapidly. It is capable of achieving pressures in excess of 10 GPa while allowing
      measurements to be performed with the maximum sensitivity of the magnetometer.
      The performance of the pressure cell is illustrated by a high pressure magnetic
      study of Mn(3)[Cr(CN)(6)](2) x xH(2)O Prussian blue analog up to 10.3 GPa.

PMID- 20687741
TI  - Deconvolution of charged particle spectra from neutron depth profiling using
      Simplex method.
AB  - Neutron depth profiling (NDP), based on neutron induced nuclear reactions, is a
      well known, nondestructive technique for the determination of the concentration
      depth profiles of some isotopes in the surface layers of solids. The profile
      determination consists of deconvolution of a relevant part of the energy spectra
      of the charged reaction products. Several solutions have been suggested for this
      problem. In this work, an alternative computer code (LIBOR), which makes use of
      the Simplex minimization technique for the deconvolution of the NDP spectra, is
      described and its performance is documented on several examples.

PMID- 20687742
TI  - Electrochemical cell for neutron reflectometry studies of the structure of ionic
      liquids at electrified interface.
AB  - We describe the design and use of a closed three-electrode electrochemical cell
      for neutron reflectometry studies of the structure of the electrical double-layer
      in ionic liquids. A transparent glass counter electrode was incorporated to allow
      easy monitoring of any gas bubbles trapped in the cell. A 100 mm diameter silicon
      wafer polished to 0.1 nm rms roughness coated with gold over a chromium adhesion
      layer was used as the working electrode. The utility of the cell was demonstrated
      during neutron reflectometry measurements of the ultrahigh purity ionic liquid 1
      butyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide
      ([C(4)mpyr][NTf(2)]) at two different applied potentials.

PMID- 20687743
TI  - Experimental study of pancreaticojejunostomy completed using anastomotic chains.
AB  - The most difficult, time-consuming, and complication-prone step in
      pancreaticoduodenectomy is the pancreaticojejunostomy step. The largest
      disadvantage of this kind of anastomosis is the high incidence of postoperative
      anastomotic leakage. Once pancreatic leakage occurs, the patient death rate can
      be very high. The aim of this study was to design a pancreaticojejunostomy
      procedure using anastomotic chains, which results in the cut end of the jejunum
      being attached to the pancreatic stump without suturing, and to evaluate the
      safety and efficacy of this procedure in domestic pigs. The pancreaticojejunal
      anastomotic chains had the following structures: the chains consisted of two
      braceletlike chains made of titanium, named chain A and chain B. The function of
      chain A was to attach the free jejunal end onto the pancreatic stump, whereas the
      function of chain B was to tighten the contact between the jejunal wall and the
      surface of the pancreatic stump to eliminate gaps between the two structures and
      ensure tightness that is sufficient to guarantee that there is no leakage of
      jejunal fluid or pancreatic juice. The following procedure was used to assess the
      safety and efficacy of the procedure: pancreaticojejunostomies were performed on
      ten domestic pigs using anastomotic chains. The time required to complete the
      pancreaticojejunal anastomoses, the pressure tolerance of the pancreaticojejunal
      anastomoses, the pig death rate, and the histopathological examinations of the
      pancreaticojejunostomy tissues were recorded. The average time required to
      complete the pancreaticojejunal anastomosis procedure was 13+/-2 min. The
      observed tolerance pressure of the pancreaticojejunal anastomoses was more than
      90 mm H(2)O. All ten domestic pigs that underwent operations were still alive
      four weeks after the operations. Pathological examinations showed that the
      anastomotic surfaces were completely healed, and the pancreatic cutting surfaces
      were primarily epithelialized. In conclusion, the use of anastomotic chains in
      pancreaticojejunostomy procedures results in a decrease in or elimination of
      pancreatic leakage. In addition, the procedure is simple to perform, is not time
      intensive, and appears to be safe in a pig model.

PMID- 20687744
TI  - Development of a multitarget tracking system for paramecia.
AB  - This investigation develops a multitarget tracking system for the motile
      protozoa, paramecium. The system can recognize, track, and record the orbit of
      swimming paramecia within a 4 mm diameter of a circular experimental pool. The
      proposed system is implemented using an optical microscope, a charge-coupled
      device camera, and a software tool, Laboratory Virtual Instrumentation
      Engineering Workbench (LABVIEW). An algorithm for processing the images and
      analyzing the traces of the paramecia is developed in LABVIEW. It focuses on
      extracting meaningful data in an experiment and recording them to elucidate the
      behavior of paramecia. The algorithm can also continue to track paramecia even if
      they are transposed or collide with each other. The experiment demonstrates that
      this multitarget tracking design can really track more than five paramecia and
      simultaneously yield meaningful data from the moving paramecia at a maximum speed
      of 1.7 mm/s.

PMID- 20687745
TI  - Magnet polepiece design for uniform magnetic force on superparamagnetic beads.
AB  - Here we report construction of a simple electromagnet with novel polepieces which
      apply a spatially uniform force to superparamagnetic beads in an optical
      microscope. The wedge-shaped gap was designed to keep partial differential B(x)/
      partial differential y constant and B large enough to saturate the bead. We
      achieved fields of 300-600 mT and constant gradients of 67 T/m over a sample
      space of 0.5x4 mm(2) in the focal plane of the microscope and 0.05 mm along the
      microscope optic axis. Within this space the maximum force on a 2.8 microm
      diameter Dynabead was 12 pN with a spatial variation of approximately 10%. Use of
      the magnet in a biophysical experiment is illustrated by showing that gliding
      microtubules propelled by the molecular motor kinesin can be stopped by the force
      of an attached magnetic bead.

PMID- 20687746
TI  - Quartz tube extensometer for observation of Earth tides and local tectonic
      deformations at the Sopronbanfalva Geodynamic Observatory, Hungary.
AB  - In May 1990, a quartz tube extensometer was installed in the Sopronbanfalva
      Geodynamic Observatory of the Geodetic and Geophysical Research Institute (GGRI)
      of the Hungarian Academy of Sciences for recording Earth tides and recent
      tectonic movements. The paper describes the construction of the extensometer and
      a portable calibrator used for the in situ calibration of the instrument. The
      extensometer is very sensitive. Its scale factor is 2.093+/-0.032 nm/mV according
      to the highly precise calibration method developed at the GGRI. Since the
      stability of extensometers is strongly influenced by the geological structure and
      properties of the rocks in the vicinity of the recording site, the observatory
      instrument system was tested by coherence analysis between theoretical (as the
      input signal) and measured tidal data series (as the output signal). In the
      semidiurnal tidal frequency band the coherence is better than 0.95, while in the
      diurnal band it is about 0.8. Probably this is due to the fact that the noise is
      higher in the diurnal band (0.4-0.5 nstr) than in the semidiurnal band (0.19-0.22
      nstr). Coherence analysis between theoretical and measured data corrected for
      barometric changes yielded a small improvement of coherence in both frequency
      bands, while using temperature data correction, no observable improvement was
      obtained. Results of the tidal analysis also show that the observatory instrument
      system is suitable for recording very small tectonic movements. The 18 years of
      continuous data series measured by the extensometer prove the high quality of the
      extensometer. On the basis of investigations, it was pointed out that further
      efforts should be done to improve the barometric correction method and that
      correction for ocean load, as well as considering topographic and cavity effects
      are necessary to increase the accuracy of determining tidal parameters.

PMID- 20687747
TI  - Adapting TESLA technology for future cw light sources using HoBiCaT.
AB  - The HoBiCaT facility has been set up and operated at the Helmholtz-Zentrum-Berlin
      and BESSY since 2005. Its purpose is testing superconducting cavities in cw mode
      of operation and it was successfully demonstrated that TESLA pulsed technology
      can be used for cw mode of operation with only minor changes. Issues that were
      addressed comprise of elevated dynamic thermal losses in the cavity walls,
      necessary modifications in the cryogenics and the cavity processing, the optimum
      choice of operational parameters such as cavity temperature or bandwidth, the
      characterization of higher order modes in the cavity, and the usability of
      existing tuners and couplers for cw.

PMID- 20687748
TI  - Calorimetric method of ac loss measurement in a rotating magnetic field.
AB  - A method is described for calorimetric ac-loss measurements of high-T(c)
      superconductors (HTS) at 80 K. It is based on a technique used at 4.2 K for
      conventional superconducting wires that allows an easy loss measurement in
      parallel or perpendicular external field orientation. This paper focuses on ac
      loss measurement setup and calibration in a rotating magnetic field. This
      experimental setup is to demonstrate measuring loss using a temperature rise
      method under the influence of a rotating magnetic field. The slight temperature
      increase of the sample in an ac-field is used as a measure of losses. The aim is
      to simulate the loss in rotating machines using HTS. This is a unique technique
      to measure total ac loss in HTS at power frequencies. The sample is mounted on to
      a cold finger extended from a liquid nitrogen heat exchanger (HEX). The thermal
      insulation between the HEX and sample is provided by a material of low thermal
      conductivity, and low eddy current heating sample holder in vacuum vessel. A
      temperature sensor and noninductive heater have been incorporated in the sample
      holder allowing a rapid sample change. The main part of the data is obtained in
      the calorimetric measurement is used for calibration. The focus is on the
      accuracy and calibrations required to predict the actual ac losses in HTS. This
      setup has the advantage of being able to measure the total ac loss under the
      influence of a continuous moving field as experienced by any rotating machines.

PMID- 20687749
TI  - Solid-state Marx based two-switch voltage modulator for the On-Line Isotope Mass
      Separator accelerator at the European Organization for Nuclear Research.
AB  - A new circuit topology is proposed to replace the actual pulse transformer and
      thyratron based resonant modulator that supplies the 60 kV target potential for
      the ion acceleration of the On-Line Isotope Mass Separator accelerator, the
      stability of which is critical for the mass resolution downstream separator, at
      the European Organization for Nuclear Research. The improved modulator uses two
      solid-state switches working together, each one based on the Marx generator
      concept, operating as series and parallel switches, reducing the stress on the
      series stacked semiconductors, and also as auxiliary pulse generator in order to
      fulfill the target requirements. Preliminary results of a 10 kV prototype, using
      1200 V insulated gate bipolar transistors and capacitors in the solid-state Marx
      circuits, ten stages each, with an electrical equivalent circuit of the target,
      are presented, demonstrating both the improved voltage stability and pulse
      flexibility potential wanted for this new modulator.

PMID- 20687750
TI  - Simple nonlinearity evaluation and modeling of low-noise amplifiers with
      application to radio astronomy receivers.
AB  - This paper describes a comparative nonlinear analysis of low-noise amplifiers
      (LNAs) under different stimuli for use in astronomical applications. Wide-band
      Gaussian-noise input signals, together with the high values of gain required,
      make that figures of merit, such as the 1 dB compression (1 dBc) point of
      amplifiers, become crucial in the design process of radiometric receivers in
      order to guarantee the linearity in their nominal operation. The typical method
      to obtain the 1 dBc point is by using single-tone excitation signals to get the
      nonlinear amplitude to amplitude (AM-AM) characteristic but, as will be shown in
      the paper, in radiometers, the nature of the wide-band Gaussian-noise excitation
      signals makes the amplifiers present higher nonlinearity than when using single
      tone excitation signals. Therefore, in order to analyze the suitability of the
      LNA's nominal operation, the 1 dBc point has to be obtained, but using realistic
      excitation signals. In this work, an analytical study of compression effects in
      amplifiers due to excitation signals composed of several tones is reported.
      Moreover, LNA nonlinear characteristics, as AM-AM, total distortion, and power to
      distortion ratio, have been obtained by simulation and measurement with wide-band
      Gaussian-noise excitation signals. This kind of signal can be considered as a
      limit case of a multitone signal, when the number of tones is very high. The work
      is illustrated by means of the extraction of realistic nonlinear characteristics,
      through simulation and measurement, of a 31 GHz back-end module LNA used in the
      radiometer of the QUIJOTE (Q U I JOint TEnerife) CMB experiment.

PMID- 20687751
TI  - The effect of volume fraction concentration on the thermal conductivity and
      thermal diffusivity of nanofluids: numerical and experimental.
AB  - This article reports on the effect of aluminum (Al) volume fraction concentration
      on the thermal conductivity and thermal diffusivity of Al nanoparticles suspended
      in water, ethylene glycol, and ethanol based fluids prepared by the one step
      method. The Al nanoparticles were independently produced and then mixed with a
      base fluid to produce the nanoparticles suspension. The thermal conductivity and
      thermal diffusivity of the nanofluids were measured using the hot wire-laser beam
      displacement technique. The thermal conductivity and thermal diffusivity were
      obtained by fitting the experimental data to the numerical data simulated for Al
      in distilled water, ethylene glycol, and ethanol. The thermal conductivity and
      thermal diffusivity of the nanofluids increase with an increase in the volume
      fraction concentration.

PMID- 20687752
TI  - Time-resolved ellipsometry for studies of heat transfer at liquid/solid and
      gas/solid interfaces.
AB  - We describe a sensitive method for measuring time-dependent changes in refractive
      index within approximately 5 microm of an interface using off-null time-resolved
      ellipsometry and a dual-cavity femtosecond laser. The sensitivity to changes in
      refractive index is two orders of magnitude higher than conventional picosecond
      interferometry. A thin metal film on a sapphire substrate is heated by
      approximately 10 K using an ultrafast optical pump pulse; the subsequent changes
      of the phase difference deltaDelta between p and s polarized reflectivity are
      tracked using off-null ellipsometry using a time-delayed probe pulse. We
      demonstrate a sensitivity of deltaDelta approximately = 3x10(-7) deg/square
      root(Hz) using interfaces between Au and water, and Au and various gases
      including R134a, a common refrigerant. Our data for the damping rate of
      approximately 200 MHz frequency acoustic waves in O(2), N(2), and Ar at
      atmospheric pressure agree well with prior results obtained at much lower
      pressures and frequencies.

PMID- 20687753
TI  - A simple air system for temperature stabilization in the range -10 to +80 degrees
      C for use in NMR spectroscopy.
AB  - This paper proposes a design for a system of temperature stabilization within the
      range from -10 to +80+/-0.5 degrees C for NMR spectrometers which is simple and
      affordable to fabricate in a laboratory. The design utilizes a closed system of
      circulation of an air heat carrier, twofold flow around the thermostabilized
      system, cooling element on Peltier thermal modules, and a proportional-integral
      derivative regulator.

PMID- 20687754
TI  - Inductive conductivity tensor measurement for flowline or material samples.
AB  - Present-day galvanic-based electrical conductivity measurements are hampered by
      limitations and necessary corrections, especially in the domain of geological
      core analysis. Low-accuracy techniques such as crucible, two-electrode, and four
      electrode are constricted by current-path requirements, while high-accuracy
      techniques are time consuming and have limited domains of applicability. We
      present a novel apparatus capable of electrical conductivity tensor measurements
      in a noninvasive, noncontact, inductive manner with resolution from 5 mS/m.
      Inspired by the triaxial induction logging technology appearing in the oil patch
      today, our apparatus is naturally applicable in a novel way not only to
      anisotropic geological core analysis but also to arbitrary material samples and
      flowline systems.

PMID- 20687755
TI  - Power spectrum analysis with least-squares fitting: amplitude bias and its
      elimination, with application to optical tweezers and atomic force microscope
      cantilevers.
AB  - Optical tweezers and atomic force microscope (AFM) cantilevers are often
      calibrated by fitting their experimental power spectra of Brownian motion. We
      demonstrate here that if this is done with typical weighted least-squares
      methods, the result is a bias of relative size between -2/n and +1/n on the value
      of the fitted diffusion coefficient. Here, n is the number of power spectra
      averaged over, so typical calibrations contain 10%-20% bias. Both the sign and
      the size of the bias depend on the weighting scheme applied. Hence, so do length
      scale calibrations based on the diffusion coefficient. The fitted value for the
      characteristic frequency is not affected by this bias. For the AFM then, force
      measurements are not affected provided an independent length-scale calibration is
      available. For optical tweezers there is no such luck, since the spring constant
      is found as the ratio of the characteristic frequency and the diffusion
      coefficient. We give analytical results for the weight-dependent bias for the
      wide class of systems whose dynamics is described by a linear
      (integro)differential equation with additive noise, white or colored. Examples
      are optical tweezers with hydrodynamic self-interaction and aliasing, calibration
      of Ornstein-Uhlenbeck models in finance, models for cell migration in biology,
      etc. Because the bias takes the form of a simple multiplicative factor on the
      fitted amplitude (e.g. the diffusion coefficient), it is straightforward to
      remove and the user will need minimal modifications to his or her favorite least
      squares fitting programs. Results are demonstrated and illustrated using
      synthetic data, so we can compare fits with known true values. We also fit some
      commonly occurring power spectra once-and-for-all in the sense that we give their
      parameter values and associated error bars as explicit functions of experimental
      power-spectral values.

PMID- 20687756
TI  - Frequency-feature based antistrong-disturbance signal processing method and
      system for vortex flowmeter with single sensor.
AB  - Digital signal processing methods have been applied to vortex flowmeter for
      extracting the useful information from noisy output of the vortex flow sensor.
      But these approaches are unavailable when the power of the mechanical vibration
      noise is larger than that of the vortex flow signal. In order to solve this
      problem, an antistrong-disturbance signal processing method is proposed based on
      frequency features of the vortex flow signal and mechanical vibration noise for
      the vortex flowmeter with single sensor. The frequency bandwidth of the vortex
      flow signal is different from that of the mechanical vibration noise. The
      autocorrelation function can represent bandwidth features of the signal and
      noise. The output of the vortex flow sensor is processed by the spectrum
      analysis, filtered by bandpass filters, and calculated by autocorrelation
      function at the fixed delaying time and at tau=0 to obtain ratios. The frequency
      corresponding to the minimal ratio is regarded as the vortex flow frequency. With
      an ultralow-power microcontroller, a digital signal processing system is
      developed to implement the antistrong-disturbance algorithm, and at the same time
      to ensure low-power and two-wire mode for meeting the requirement of process
      instrumentation. The water flow-rate calibration and vibration test experiments
      are conducted, and the experimental results show that both the algorithm and
      system are effective.

PMID- 20687757
TI  - A high-temperature high-pressure calorimeter for determining heats of solution up
      to 623 K.
AB  - A high-temperature high-pressure isoperibol calorimeter for determining the heats
      of solution and reaction of very dilute substances in water (10(-4) m) at
      temperatures up to 623 K is described. The energies of vaporization of water at
      steam saturation pressure were measured as a function of temperature and the
      results agree with the corresponding values from steam tables to better than
      0.08+/-0.18%. The novelties of the present instrument relative to flow type heat
      capacity calorimeters are that measurements can be made at orders of magnitude
      lower concentrations and that measurement of heat of reaction involving solids or
      gases or in the presence of high concentrations of supporting electrolytes,
      acids, and bases is possible. Furthermore, the advantage of using enthalpy data
      over heat capacity data for calculations of the standard state Gibbs free
      energies of electrolytes is that the experimental heat data of this research need
      only be integrated once to derive higher temperature free energy data from lower
      temperatures. The derived heat capacities can be used mathematically to obtain
      free energies by double integration. However, the resulting errors are much
      smaller than if experimental aqueous heat capacities were used for the
      integrations.

PMID- 20687758
TI  - rf power system for thrust measurements of a helicon plasma source.
AB  - A rf power system has been developed, which allows the use of rf plasma devices
      in an electric propulsion test facility without excessive noise pollution in
      thruster diagnostics. Of particular importance are thrust stand measurements,
      which were previously impossible due to noise. Three major changes were made to
      the rf power system: first, the cable connection was changed from a balanced
      transmission line to an unbalanced coaxial line. Second, the rf power cabinet was
      placed remotely in order to reduce vibration-induced noise in the thrust stand.
      Finally, a relationship between transmission line length and rf was developed,
      which allows good transmission of rf power from the matching network to the
      helicon antenna. The modified system was tested on a thrust measurement stand and
      showed that rf power has no statistically significant contribution to the thrust
      stand measurement.

PMID- 20687759
TI  - Temperature dependent thermoelectric material power factor measurement system.
AB  - Thermoelectric materials can be used for cooling/heating applications, or
      converting waste heat into electricity. Novel thermoelectric materials have been
      discovered in recent years. Characterization of an electrical conductivity and
      thermopower of a sample from room temperature to > or = 900 K is often necessary
      for thermoelectric materials. This paper describes a system built for measurement
      of the power factor of thermoelectric materials from 300 to 1273 K.
      Characterization results of the system are also presented.

PMID- 20687760
TI  - Two-dimensional dielectric spectroscopy: implementation and validation of a
      scanning open-ended coaxial probe.
AB  - Dielectric spectroscopy is a powerful tool for characterizing and classifying
      materials based on their electrical properties. In order to perform dielectric
      measurements on a sample with spatially varying properties, the measuring probe
      typically is repositioned manually on the surface of the sample for each
      measurement. In this paper, we present a novel technique, based on a
      reconfigurable multielectrode array, which facilitates the recording of
      measurements at various different spatial locations without physically moving the
      measuring electrodes. By electronically selecting one of the electrodes as the
      inner line and connecting the remainder of the electrodes together to form the
      outer line, an open-ended coaxial probe is created, which can be repositioned by
      simply selecting different electrode combinations; hence the name of a
      "traveling" coaxial probe. The geometric factor, or the cell constant, of each
      coaxial probe in the array was estimated from measurements on saline solutions
      with known electrical characteristics. In order to validate the setup for
      measurement of dielectric properties of biological cells, the plasma membrane
      capacitance and cytoplasm conductivity of yeast cells suspended in aqueous
      solutions were measured and compared to results from published reports.
      Dielectric spectroscopy imaging was carried out on tissue phantoms made of an
      agar gel with inclusions consisting of concentrated yeast cell suspensions.
      Measurements were performed on the phantoms, and the dielectric data were
      spatially mapped with respect to electrode location. The spatial electrical data
      correlated precisely with locations of yeast cell inclusions within the phantoms.

PMID- 20687761
TI  - Fast scanning cavity offset lock for laser frequency drift stabilization.
AB  - We have implemented a compact setup for long-term laser frequency stabilization.
      Light from a stable reference laser and several slave lasers is coupled into a
      confocal Fabry-Perot resonator. By stabilizing the position of the transmission
      peaks of the slave lasers relative to successive peaks of the master laser as the
      length of the cavity is scanned over one free spectral range, the long-term
      stability of the master laser is transferred to the slave lasers. By using fast
      analog peak detection and low-latency microcontroller-based digital feedback,
      with a scanning frequency of 3 kHz, we obtain a feedback bandwidth of 380 Hz and
      a relative stability of better than 10 kHz at timescales longer than 1 s, a
      significant improvement on previous scanning-cavity stabilization systems.

PMID- 20687762
TI  - A new magnetron based gas aggregation source of metal nanoclusters coupled to a
      double time-of-flight mass spectrometer system.
AB  - A new magnetron based gas-aggregation source for continuous production of metal
      nanoclusters has been built and coupled to a double time-of-flight mass
      spectrometer system. The capability of the source to produce neutral, positive,
      and negative nanoclusters within one production cycle, particularly under the
      same optimized experimental conditions, has been tested. The source performs
      steadily for continuous long operations and has high beam intensity that would be
      preferable for size selective measurements in gas phase on individual
      nanoclusters. This paper describes on the instrumentation of the integrated
      complete experimental setup for gas-phase measurement on nanoclusters including
      the source. It reports on the production of copper nanoclusters using the source.
      Mass abundances of neutral and charged clusters have been investigated and the
      results are discussed with respect to reported results using various other types
      of sources. The experimental isotopic distributions of (63)Cu versus (65)Cu
      within individual cluster mass peaks have been derived and compared to
      corresponding theoretical profiles.

PMID- 20687763
TI  - Stand alone experimental setup for dc transport measurements.
AB  - Described is a system consisted of Keithley's current source Model 6221 and
      nanovoltmeter Model 2182A pairs. That pair was developed by Keithley for precise
      measurements of a sample's one electrical parameter by the dc current-reversal
      transport technique. Nonstandard synchronization method employed in the presented
      setup allows assembling several pairs together for low level electrical
      measurements of a sample's several parameters associated with the same current,
      thus expanding the applications of these devices. The equipment was tested by
      simultaneous measurements of such two parameters as transverse magnetoresistance
      and Hall voltage on the following materials: Si/SiGe, Ge:Mn; HgTe/HgCdTe, and
      InMnSb.

PMID- 20687764
TI  - Symmetric miniaturized heating system for active microelectronic devices.
AB  - To qualify interconnect technologies such as microelectronic fine wire bonds for
      mass production of integrated circuit (IC) packages, it is necessary to perform
      accelerated aging tests, e.g., to age a device at an elevated temperature or to
      subject the device to thermal cycling and measure the decrease of interconnect
      quality. There are downsides to using conventional ovens for this as they are
      relatively large and have relatively slow temperature change rates, and if
      electrical connections are required between monitoring equipment and the device
      being heated, they must be located inside the oven and may be aged by the high
      temperatures. Addressing these downsides, a miniaturized heating system
      (minioven) is presented, which can heat individual IC packages containing the
      interconnects to be tested. The core of this system is a piece of copper cut from
      a square shaped tube with high resistance heating wire looped around it. Ceramic
      dual in-line packages are clamped against either open end of the core. One
      package contains a Pt100 temperature sensor and the other package contains the
      device to be aged placed in symmetry to the temperature sensor. According to the
      temperature detected by the Pt100, a proportional-integral-derivative controller
      adjusts the power supplied to the heating wire. The system maintains a dynamic
      temperature balance with the core hot and the two symmetric sides with electrical
      connections to the device under test at a cooler temperature. Only the face of
      the package containing the device is heated, while the socket holding it remains
      below 75 degrees C when the oven operates at 200 degrees C. The minioven can heat
      packages from room temperature up to 200 degrees C in less than 5 min and
      maintain this temperature at 28 W power. During long term aging, a temperature of
      200 degrees C was maintained for 1120 h with negligible resistance change of the
      heating wires after 900 h (heating wire resistance increased 0.2% over the final
      220 h). The device is also subjected to 5700 thermal cycles between 55 and 195
      degrees C, demonstrating reliability under thermal cycling.

PMID- 20687765
TI  - A test cassette for x-ray-exposure experiments at the National Ignition Facility.
AB  - We present the design and operation of a test cassette for exposure of samples to
      radiation environments at the National Ignition Facility. The cassette provides
      options for square and round samples and exposure areas; the cassette provides
      for multiple levels of filtration on a single sample, which allows dynamic range
      in experiments. The samples had normal lines of sight to the x-ray source in
      order to have uniform x-ray illumination. The incident x-radiation onto the
      samples was determined by the choice of filter thicknesses and materials. The
      samples were held at precise locations, accurate to within a few hundred microns,
      in the target chamber in order to have a known fluence incident. In the cassette,
      the samples were held in place in such a way that a minimal "line contact" allows
      them to have the maximal mechanical response to the x-ray load. We present
      postshot images of the debris found on films used for filters, and pre- and
      postexposure specimens.

PMID- 20687766
TI  - Global Event-identifier Module: a distributed digital approach to event-of
      interest identification logic for physics experiments.
AB  - The demands from current data acquisition systems are to acquire data from a
      large number of detectors (or signals) while providing a high throughput. This
      can be achieved by having some preprocessing capability in the data acquisition
      system so that it can identify the events of interest. Precise selection of
      events with minimal time for identification and preprocessing is an experimental
      challenge. To address this challenge, we have developed a "Global Event
      identifier Module" (GEM) on the CAMAC platform, which can flexibly adapt to the
      experimental requirements and validate an event with minimal time. GEM is a
      single width CAMAC module capable of operating in a "distributed" data
      acquisition environment where multiple CAMAC crates (each with one GEM module)
      can be used to collect synchronized data from all the crates. Event-of-interest
      decision can be made on signals connected to different crates. Inter-GEM
      communication is via the ubiquitous ethernet (unshielded twisted pair, CAT5)
      cable. The event of interest is decided within 32 ns (excluding cable delay).
      Implementation is accomplished using field programmable gate array which enables
      greater flexibility for algorithm modifications and updates without hardware
      changes. GEM supports unified, distributed, and multi-strobe data acquisition,
      enabling higher throughput, with data collection from a large number of signals
      by selective reads of events of interest as determined by the experimenter while
      providing timestamped data of each event.

PMID- 20687767
TI  - Note: Supplements and corrections to the generalized conic flexure hinge model.
AB  - Some supplementary equations have been provided for the generalized model for
      conic flexure hinges [G. Chen et al., Rev. Sci. Instrum. 80, 055106 (2009)] for
      the purpose of avoiding division-by-zero issues (having zeros in their
      denominators) in programming languages such as MATLAB, C, and FORTRAN. Some typos
      have been corrected as well. In comparison, these equations are more concise and
      effective.

PMID- 20687768
TI  - Note: New design of a cryogenic linear radio frequency multipole trap.
AB  - A new design of a cryogenic linear 22-pole ion trap has been constructed and
      tested. It is essentially a copper housing to which opposite inner walls two
      electrode sets are attached via sapphire insulators. These stainless steel
      electrodes are electroformed in one piece to guarantee good heat conduction.
      Connected to an external coil, they form an LC-circuit of about 19 MHz resonance
      frequency. This circuit is excited with a rf power supply made of a commercial
      digital synthesizer followed by a 10 W amplifier. Buffer gas-cooled H(2)D(+) ions
      have been stored in this trap at a nominal trap temperature of 14 K. Spectroscopy
      of the ions confirmed that the kinetic (Doppler) temperature is in reasonable
      agreement with this value.

PMID- 20687769
TI  - Note: Microelectromechanical systems Coulter counter for cell monitoring and
      counting.
AB  - This note describes the design, fabrication, and testing of a novel
      microelectromechanical systems Coulter counter. The Coulter counter will be used
      to detect and monitor impedance changes of cells as a function of time in
      response to different experimental extracellular environments. The device
      consists of SU-8 (negative photoresist) microchannels, vertical electroplated
      electrodes, polydimethylsiloxane cover, and is divided into a passive mixing
      region, a focusing region using negative dielectrophoretic forces, and a
      measuring region defined by multiple electroplated electrode pairs. The devices
      were tested using both microbeads in saline water and fibroblast cells in
      phosphate buffered saline solution. The results show that the proposed
      microsystem is capable of monitoring impedance of cells at different positions
      along the Coulter microchannel.

PMID- 20687770
TI  - Note: A thermally stable tension meter for atmospheric soundings using kites.
AB  - Kites offer considerable potential as wind speed sensors--a role distinct from
      their traditional use as instrument-carrying platforms. In the sensor role, wind
      speed is measured by kite-line tension. A kite tether line tension meter is
      described here, using strain gauges mounted on an aluminum ring in a Wheatstone
      bridge electronic circuit. It exhibits a linear response to tension (19.5 mV N(
      1)) with good thermal stability (mean drift of -0.18 N degrees C(-1) over 5-45
      degrees C temperature range) and a rapid time response (0.2 s or better). Field
      comparisons of tether line tension for a Rokkaku kite with a fixed tower sonic
      anemometer show an approximately linear tension-wind speed relationship over the
      range 1-6 ms(-1).

PMID- 20687771
TI  - Note: Thermal properties of magnesium in the 60-150 mK range.
AB  - Refrigerators for space and other applications working around 100 mK require
      lightweight components with good thermal properties. We have measured the thermal
      properties of high-purity (99.95%) magnesium, which is five times lighter than
      copper, over the 60-150 mK range and found that it is well-behaved down to these
      temperatures. Both conductivity and heat capacity are in good agreement with
      extrapolations from measurements at higher temperatures. The heat capacity per
      unit volume is about the same as copper and the thermal conductivity about 2.7
      times lower than copper of similar residual resistivity ratio, as expected from
      magnesium's higher room-temperature resistivity.

PMID- 20687773
TI  - Effects of nitrous acid exposure on pulmonary tissues in guinea pigs.
AB  - Many epidemiological studies on the effects of nitrogen dioxide (NO(2)) on
      respiratory function may have included nitrous acid (HONO) exposures in their
      measures, because conventional NO(2) assays detect HONO as NO(2). A few
      epidemiological studies and human HONO inhalation experiments have associated
      HONO with decrements in lung functions. However, there have been few HONO
      exposure experiments in animals. This study aims to develop a HONO generation
      system for the animal exposure experiments, and to assess the association of HONO
      exposure with histopathologic alterations in the respiratory tract of guinea
      pigs. We exposed the guinea pigs to 3.6 ppm HONO with secondary products of 0.3
      ppm NO(2) and 1.6 ppm nitric oxide (NO) for 4 weeks (24 h/day). We conducted
      histopathologic analyses and measured specific airway resistance (sRaw) from 7 h
      40 min to 8 h 30 min after the end of HONO exposure. We found pulmonary emphysema
      like alterations in the alveolar duct centriacinar regions, distortion of the
      centriacinar regions of alveolar ducts with extension of the bronchial epithelial
      cells and smooth muscle cells, and expansion of bronchial epithelial cells, in
      the HONO exposure. These histopathologic results suggest that a high
      concentration of HONO with some NO(2) and NO may associate with decrements in
      lung functions and some respiratory symptoms. Although the increased tendency of
      the sRaw value was observed in the HONO exposure group, no statistically
      significant difference was found between the sRaw values from the HONO exposure
      group and the filtered air group (p = 0.06, student's t-test).

PMID- 20687774
TI  - Comparison between nuclear magnetic resonance profiling and the source/sink
      approach for characterizing drug diffusion in hydrogel matrices.
AB  - In controlled drug delivery, the drug diffusion coefficient in a given matrix is
      a key factor for predicting its release rate. In this work, we compare (31)P
      nuclear magnetic resonance (NMR) profiling for obtaining the mutual-diffusion
      coefficient (D(m)(gel)) of a drug in hydrogel with results obtained from
      conventional source/sink experiments. Despite the fact that NMR profiling is a
      powerful approach for measuring transport properties, it is rarely used for
      characterizing drug diffusion in gel matrices in pharmaceutical sciences. This
      work provides an illustration of the applicability of this technique and
      highlights its advantages for studying drug release systems. The comparison with
      results obtained from the source/sink experiment clearly establishes the validity
      of the NMR profiling approach. Alendronate was used as a model drug while
      curdlan, a gel-forming bacterial polysaccharide, served as a model biomaterial.
      The determined (D(m)(gel)) value (5.6 +/- 0.3 * 10(-10) m(2)/s) agrees with the
      one obtained from a conventional source/sink experiment (5.4 +/- 0.5 * 10(-10)
      m(2)/s). In addition, the alendronate self-diffusion coefficients in solution
      (D(s)(sln)) and in the hydrogel (D(s)(gel)) were measured on the same system
      using pulse-field gradient (PFG) (31)P NMR. These supplementary parameters
      provided a more detailed characterization of the drug transport properties in the
      gel matrix.

PMID- 20687776
TI  - Drastic effects of cryoglobulin on blood cell counts, erythrocyte morphology and
      M-protein analysis.

PMID- 20687775
TI  - Modeling tissue growth within nonwoven scaffolds pores.
AB  - In this study we present a novel approach for predicting tissue growth within the
      pores of fibrous tissue engineering scaffolds. Thin nonwoven polyethylene
      terephthalate scaffolds were prepared to characterize tissue growth within
      scaffold pores, by mouse NR6 fibroblast cells. On the basis of measurements of
      tissue lengths at fiber crossovers and along fiber segments, mathematical models
      were determined during the proliferative phase of cell growth. Tissue growth at
      fiber crossovers decreased with increasing interfiber angle, with exponential
      relationships determined on day 6 and 10 of culture. Analysis of tissue growth
      along fiber segments determined two growth profiles, one with enhanced growth as
      a result of increased tissue lengths near the fiber crossover, achieved in the
      latter stage of culture. Derived mathematical models were used in the development
      of a software program to visualize predicted tissue growth within a pore. This
      study identifies key pore parameters that contribute toward tissue growth, and
      suggests models for predicting this growth, based on fibroblast cells. Such
      models may be used in aiding scaffold design, for optimum pore infiltration
      during the tissue engineering process.

PMID- 20687777
TI  - Assessment of new application system in Portuguese patients with relapsing
      remitting multiple sclerosis.
AB  - OBJECTIVE: To evaluate the satisfaction level of multiple sclerosis (MS) patients
      treated with interferon beta-1b (IFNbeta-1b, Betaferon*) using a newly developed
      application system compared to their currently used application system. METHODS:
      A survey was conducted in Portugal in patients treated with IFNbeta-1b for
      relapsing-remitting MS with the Betaject or Betaject Lite autoinjector. Nurses
      demonstrated the new application system and supervised the first injection.
      Patients rated their overall satisfaction retrospectively with their current
      application system and prospectively after the first, the seventh and the 15th
      injection with the newly developed application system. Additionally, the ease of
      use was evaluated for both application systems using a questionnaire consisting
      of 13 questions. Responses were compiled and descriptive analyses performed.
      RESULTS: A total of 249 patients evaluated the current and the new system after
      the first, 235 after the seventh and 174 after the 15th injection. The
      satisfaction level was high with the current system (70.3%, 'satisfied' or 'very
      satisfied'). However, compared with the current system, more patients were either
      'satisfied' or 'very satisfied' (98%) with the new system after first injection.
      Only a minority of patients rated 'somewhat satisfied': 2.0% after the first,
      8.6% after the seventh, and 4.4% after the 15th injection. Increased overall
      satisfaction level ('satisfied' or 'very satisfied') with the newly developed
      system was maintained over time (98% - first, 90.5% - seventh, 93.8% - 15th
      injection). The thinner, pre-attached 30-gauge needle and the visual signalling
      of injection completion were among the changes considered as strong improvements
      to the new system by up to 80.3% of patients. LIMITATION: Retrospective analysis
      of current system. CONCLUSIONS: This survey documented patient satisfaction with
      different application systems of IFNbeta-1b. The increased satisfaction with the
      new application system indicates an improvement to the currently used injection
      system, which may contribute to further advancement in adherence and consequently
      higher clinical efficacy of treatment.

PMID- 20687778
TI  - Therapeutic management of premenstrual syndrome.
AB  - IMPORTANCE OF THE FIELD: Premenstrual syndrome (PMS) is among the most common
      health problems reported by reproductive-age women. Estimates indicate that up to
      25% of women may warrant treatment for the distress or impaired functioning
      associated with the symptoms. AREAS COVERED IN THIS REVIEW: The primary focus of
      this review is the clinical condition of PMS and randomized, placebo-controlled
      trials of PMS treatment. A literature search in PubMed was conducted for these
      topics. The most recent reports of specific treatments in controlled treatment
      studies and all meta-analyses were selected. WHAT THE READER WILL GAIN: Reports
      consistently indicate that serotonergic antidepressants reduce PMS symptoms
      compared to a placebo. Hormonal treatments are the most widely prescribed medical
      treatment. Some oral contraceptives and gonadotropin-releasing hormone analogs
      have demonstrated efficacy, particularly for women who want contraception and PMS
      symptom control. Numerous non-pharmacologic treatments are utilized, but efficacy
      is reported only for calcium supplements, Vitex agnus castus (chasteberry), and
      cognitive-behavioral therapies. Further research to develop new therapies for the
      40% of women with PMS who do not respond to the currently available treatments is
      needed. TAKE HOME MESSAGE: There are treatments with demonstrated efficacy for
      PMS, and the majority of women can be helped.

PMID- 20687779
TI  - Approaches to neuroprotective strategies in multiple sclerosis.
AB  - IMPORTANCE OF THE FIELD: Multiple sclerosis (MS) is a neurologic disease that is
      the most common nontraumatic cause of serious disability in young adults. AREAS
      COVERED IN THIS REVIEW: We discuss the natural history of the disease, methods of
      measuring disease activity and burden, and cellular and molecular mechanisms of
      damage, in particular recent advances. These imply new therapeutic targets, which
      are beginning to be tested in animal models of MS as well as in patients. WHAT
      THE READER WILL GAIN: The reader will learn about some recent advances in
      understanding MS, especially the evolution from an inflammatory phase to a
      neurodegenerative phase, which have different therapeutic approaches. TAKE HOME
      MESSAGE: MS has a long-term course of accumulating deficit in which
      neuroinflammation evolves into neurodegeneration, which require different
      treatment strategies - immune modulation and neuroprotection. Neuroprotective
      strategies are still under development.

PMID- 20687780
TI  - Prevalence of angiotensin-converting enzyme, methylenetetrahydrofolate reductase,
      Factor V Leiden, prothrombin and apolipoprotein E gene polymorphisms in Morocco.
AB  - BACKGROUND: Evidence of the influence of genetic risk factors on cardiovascular
      diseases is more or less established. These genetic factors are involved in
      several pathways affecting blood pressure regulation, blood coagulation,
      homocysteine and lipid metabolisms. AIM: We evaluated frequencies of five genetic
      polymorphisms to assess their informativeness as markers for prospective clinical
      studies. SUBJECTS AND METHODS: 182 healthy Moroccan subjects were genotyped for
      ACE I/D by amplification alone and by amplification followed by enzymatic
      digestion for other polymorphisms. RESULTS: Allele frequencies of ACE ID, MTHFR
      C677T were 76.6%, 26.9% for D and T alleles, respectively. APOE polymorphism
      showed 11.3%, 78.6% and 10.2% for the alleles E2, E3 and E4, respectively. The
      frequency for FII G20210A polymorphism was around 2.7% for A allele. Our data
      showed an absence of FVL mutation. Using allele frequencies, genetic distances
      between Moroccan and other populations revealed an independent variability of
      these polymorphisms. CONCLUSION: These values appear to be influenced by findings
      in European and African peoples, and may be considered in assessing the clinical
      significance of a predisposition to cardiovascular disease.

PMID- 20687782
TI  - Overview perspective of bacterial resistance.
AB  - The rapidly escalating prevalence of antimicrobial resistance is a global
      concern. This reduced susceptibility to currently available antimicrobial agents
      coupled with the progressive shortage of newly approved compounds is a worrisome
      situation. Major problems are encountered for a growing number of Gram-positive
      (i.e., Staphylococcus aureus, Streptococcus pneumoniae, Enterococcus spp.) and
      Gram-negative pathogens (i.e., Pseudomonas aeruginosa, Acinetobacter baumannii,
      Klebsiella pneumoniae). We provide an overview of bacterial resistance focusing
      on the most common pathogens responsible for infection in both the community and
      healthcare settings. In addition, several strategies to curb antimicrobial
      resistance are also discussed. It is increasingly evident that without the
      introduction of novel antimicrobial agents, a return to the clinical outcomes
      associated with the pre-antibiotic era are inevitable.

PMID- 20687781
TI  - Stem cell therapy for ischemic heart disease.
AB  - Stem cell transplantation has emerged as a novel treatment option for ischemic
      heart disease. Different cell types have been utilized and the recent development
      of induced pluripotent stem cells has generated tremendous excitement in the
      regenerative field. Bone marrow-derived multipotent progenitor cell
      transplantation in preclinical large animal models of postinfarction left
      ventricular remodeling has demonstrated long-term functional and bioenergetic
      improvement. These beneficial effects are observed despite no significant
      engraftment of bone marrow cells in the myocardium and even lower differentiation
      of these cells into cardiomyocytes. It is thought to be related to the paracrine
      effect of these stem cells, which secrete factors that lead to long-term gene
      expression changes in the host myocardium, thereby promoting neovascularization,
      inhibiting apoptosis, and stimulating resident cardiac progenitor cells. Future
      studies are warranted to examine the changes in the recipient myocardium after
      stem cell transplantation and to investigate the signaling pathways involved in
      these effects.

PMID- 20687784
TI  - Molecular targeted therapy for patients with melanoma: the promise of MAPK
      pathway inhibition and beyond.
AB  - IMPORTANCE OF THE FIELD: Recent discoveries have expanded the understanding of
      the molecular signaling events critical to melanomagenesis and led to the
      development of targeted therapeutic agents that are revolutionizing the treatment
      of patients with advanced melanoma. AREAS COVERED IN THIS REVIEW: This article
      reviews current therapy and its limitations, describes the key pathogenic
      mechanisms in melanoma for which inhibitors have been tested, and summarizes the
      results of clinical trials involving molecularly targeted agents in this disease.
      WHAT THE READER WILL GAIN: There has been an explosion of preclinical and
      clinical research aimed at targeting the key molecular alterations in melanoma
      for therapeutic benefit. These findings will be presented and placed in the
      proper clinical context, affording information regarding the current molecular
      targets in the melanoma and the activity and limitations of therapeutic agents
      directed against them. TAKE HOME MESSAGE: Greater understanding of the pathogenic
      mechanisms underlying melanoma development has prompted the development of new
      therapeutic approaches aimed at counteracting these processes. While progress
      made over the past few years has generated considerable excitement, the benefits
      of these new therapies are still limited by incomplete and transient tumor
      regressions. It is hoped that with further investigation, particularly into
      mechanisms of treatment de novo and acquired treatment resistance, these
      limitations can be overcome.

PMID- 20687785
TI  - Lacosamide for pain.
AB  - IMPORTANCE OF THE FIELD: Neuropathic pain remains a condition that is difficult
      to treat and with which therapeutic failure is not uncommon. The need for new and
      effective drugs to treat neuropathic pain remains strong. AREAS COVERED IN THIS
      REVIEW: The available preclinical and clinical data for the pain relieving effect
      of lacosamide have been examined using the papers published and referenced on
      Medline between 1990 and present. WHAT THE READER WILL GAIN: It is hoped that
      readers will gain an insight into the use of this novel analgesic agent in human
      clinical pain. TAKE HOME MESSAGE: The data relating to the pain relieving effect
      of lacosamide are sparse. The majority of the published human data relate to the
      use of lacosamide for the treatment of painful diabetic neuropathy where the
      extent of pain relief produced has not been deemed sufficient to warrant an
      application for a product license for this indication. That said, it is suggested
      that there remains merit in further investigation of this drug for other
      neuropathic pain conditions.

PMID- 20687783
TI  - The clinical development of histone deacetylase inhibitors as targeted anticancer
      drugs.
AB  - IMPORTANCE OF THE FIELD: Histone deacetylase (HDAC) inhibitors are being
      developed as a new, targeted class of anticancer drugs. AREA COVERED IN THIS
      REVIEW: This review focuses on the mechanisms of action of the HDAC inhibitors,
      which selectively induce cancer cell death. WHAT THE READER WILL GAIN: There are
      11 zinc-dependent HDACs in humans and the biological roles of these lysine
      deacetylases are not completely understood. It is clear that these different
      HDACs are not redundant in their activity. This review focuses on the mechanisms
      by which HDAC inhibitors can induce transformed cell growth arrest and cell
      death, inhibit cell mobility and have antiangiogenesis activity. There are more
      than a dozen HDAC inhibitors, including hydroxamates, cyclic peptides, benzamides
      and fatty acids, in various stages of clinical trials and many more compounds in
      preclinical development. The chemically different HDAC inhibitors may target
      different HDACs. TAKE HOME MESSAGE: There are extensive preclinical studies with
      transformed cells in culture and tumor-bearing animal models, as well as limited
      clinical studies reported to date, which indicate that HDAC inhibitors will be
      most useful when used in combination with cytotoxic or other targeted anticancer
      agents.

PMID- 20687786
TI  - Antidiabetic effect of Raphanus sativus root juice.
AB  - CONTEXT: Many plants have been explored scientifically and systematically and
      claimed to be useful for the treatment of diabetes mellitus by various research
      groups worldwide. The present study is a further effort in the direction of
      developing a novel oral antidiabetic agent of high potential with minimal or no
      side effects. OBJECTIVE: This study screened the glycemic attributes of Raphanus
      sativus L. (Brassicaceae) root juice in normal as well as sub- and mild-diabetic
      models. MATERIALS AND METHODS: The variable doses of 100, 200, 300, and 400 mg
      kg(-1) body weight (bw) of the extract were administered orally to normal and
      streptozotocin (STZ)-induced sub- and mild-diabetic rats in order to define its
      glycemic potential. Glibenclamide was used as a reference drug. RESULTS: The dose
      of 300 mg kg(-1)bw was identified as the most effective dose which lowers the
      blood glucose level (BGL) by 33.4% (p < 0.001) at 6 h during fasting blood
      glucose (FBG) studies in normal rats. However, the glucose tolerance test (GTT)
      revealed the maximum reduction of 15.9% (p < 0.001) in BGL at 3 h in normal rats
      with the same dose, whereas the reduction observed was by 23.8 and 28.3% (p <
      0.001) in sub- and mild-diabetic rats, respectively, at the same interval of
      time. DISCUSSION AND CONCLUSION: This evidence clearly indicates that Raphanus
      sativus root juice possesses good hypoglycemic potential coupled with
      antidiabetic efficacy.

PMID- 20687787
TI  - Protective effects of baicalin on carbon tetrachloride induced liver injury by
      activating PPARgamma and inhibiting TGFbeta1.
AB  - CONTEXT: Traditional Chinese herbal medicines have attracted considerable
      attention in many countries with treatment of several end-stage liver diseases.
      OBJECTIVE: The present study investigated the protective effects of baicalin on
      hepatotoxicity and hepatic fibrosis and explored the role of transforming growth
      factor beta1 (TGFbeta1) and peroxisome proliferator activated receptors gamma
      (PPARgamma) on the rat liver injury model. MATERIALS AND METHODS: The rat liver
      injury model was introduced by subcutaneous injection of carbon tetrachloride
      (CCl(4)) for 8 weeks. At week 5, rats were treated with baicalin of different
      doses or silymarin. Detection of biochemical indicators, histological analysis,
      and enzyme-linked immunosorbent assays were employed to evaluate severity of
      liver inflammation, and western blotting and RT-PCR assay were performed to
      evaluate TGFbeta1 and PPARgamma pathway related proteins and gene expression.
      RESULTS: The administration of baicalin could significantly improve histological
      changes of CCl(4) treated rat livers and return biochemical indicators for liver
      injury to nearly baseline level. In addition, the increased expression of
      TGFbeta1 was markedly suppressed by baicalin, and decreased expression of
      PPARgamma was also dramatically elevated by baicalin as well. The
      hepatoprotective effects of baicalin may be conferred by elevating the level of
      PPARgamma contributing to down-regulation of TGFbeta1 signaling pathway and
      suppression of hepatic stellate cell activation. CONCLUSIONS: The studies
      demonstrated that baicalin is a potent and promising antifibrotic drug in the
      treatment of hepatic fibrosis.

PMID- 20687788
TI  - Plasmodesmata: gateways to local and systemic virus infection.
AB  - As channels that provide cell-to-cell connectivity, plasmodesmata are central to
      the local and systemic spread of viruses in plants. This review discusses the
      current state of knowledge of the structure and function of these channels and
      the ways in which viruses bring about functional changes that allow
      macromolecular trafficking to occur. Despite the passing of two decades since the
      first identification of a viral movement protein that mediates these changes, our
      understanding of the relevant molecular mechanisms remains in its infancy.
      However, viral movement proteins provide valuable tools for the modification of
      plasmodesmata and will continue to assist in the dissection of plasmodesmal
      properties in relation to their core roles in cell-to-cell communication.

PMID- 20687789
TI  - Immunomodulatory activity of Aegle marmelos in freshwater fish (Catla catla) by
      non-specific protection.
AB  - CONTEXT: The production of fish is limited by infectious diseases; when a fish
      grows in an immunosuppressed condition, it becomes highly susceptible to disease.
      OBJECTIVE: The present research work investigates immunomodulatory action of
      Aegle marmelos (Linn.) Corr. Serr. (Rutaceae) in Catla catla Hamilton
      (Cyprinidae) for enhancing immune protection of the fish against bacterial
      infections. MATERIAL AND METHODS: Doses of 0, 5, 10, 15, 20, 25 and 30 g aqueous
      plant leaf extract/kg feed were administered orally to the freshwater fish, Catla
      catla for a period of 30 days to investigate its efficiency to enhance the non
      specific immune responses against the fish pathogen Pseudomonas aeruginosa
      (Schroter) Migula (Pseudomonadaceae). RESULTS AND DISCUSSION: The fish were
      challenged with pathogens through water medium for 30 days and the
      immunomodulatory effect of the Aegle marmelos was evaluated on the blood samples
      every 5 days until 15 days after infection. The results obtained from the study
      shows that the 25 g leaf extract/kg of feed was found to be competent to enhance
      optimum immune response. The effectiveness of the immunostimulant action was
      found to be best for the first 5 days after challenging with pathogen and
      subsequently, the immune response was found to decline in all the concentrations
      of plant extract. CONCLUSION: The results of the study will be helpful for
      further investigation in the field to improve the immunocompetence of fish
      against bacterial pathogens.

PMID- 20687790
TI  - Activated fly ash catalyzed facile synthesis of novel spiro imidazolidine
      derivatives as potential antibacterial and antifungal agents.
AB  - An array of novel spiro imidazolidine derivatives was synthesized in dry media
      and was screened for their anti-microbial activities. Structure-activity
      relationship results revealed that compounds 22, 23 against P.aeruginosa, 24
      against S.aureus, 24, 25 against K.pneumonia, 27 against S.aureus, beta
      H.streptococcus, 29 against M.luteus, K.pneumonia, 29, 30 against P.vulgaris
      exhibited excellent antibacterial activity at a minimum inhibitory concentration
      (MIC) value of 6.25 ug/mL. Compound 23 against M.gypseum, 25, 29 against Candida
      6 and 29, 30 against C.albicans revealed excellent antifungal activity at a MIC
      value of 6.25 ug/mL.

PMID- 20687791
TI  - Synthesis and antidiabetic activity of some new chromonyl-2,4-thiazolidinediones.
AB  - A series of chromonyl-2,4-thiazolidinediones/imidazolidinediones/2-thioxo
      imidazolidine-4-ones (IIIa-i, IVa-i) was prepared by Knoevenagel reaction of 2,4
      thiazolidinedione/2,4-imidazolidinedione/2-thioxo-imidazolidine-4-one (IIa-c)
      with 2/3-formyl chromone (Ia-b) and then alkylation with methyl/ethyl iodide. The
      prepared compounds were tested for their insulinotropic activities in INS-1
      cells. Compounds iVb and iVc (at lower concentration, 1 MUg/mL) were able to
      increase insulin release in the presence of 5.6 mmol/L glucose." should be
      written as "Compounds IVb and IVc (at lower concentration, 1 ug/mL) and also IIId
      and IIIg (at higher concentration) were able to increase insulin release in the
      presence of 5.6 mmol/L glucose. Compounds iVb and iVc (at lower concentration, 1
      MUg/mL) were able to increase insulin release in the presence of 5.6 mmol/L
      glucose.

PMID- 20687792
TI  - Honey, pollen, and propolis extracts show potent inhibitory activity against the
      zinc metalloenzyme carbonic anhydrase.
AB  - Three different honey extracts from the endemic plant in the Black Sea region
      Rhododendron ponticum, were investigated for their inhibitory effects against the
      metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1), more precisely the human (h)
      isoforms hCA I and hCA II. Hexane, methanol, ethanol, and water solid-phase
      extractions (SPEs) showed inhibitory activity towards the two CA isozymes which
      were related to the total phenolic content. The highest inhibitory effects (0.036
      0.039 mg/mL) were those of propolis methanolic extract. Among the three different
      samples investigated here, the aqueous extracts showed lower inhibitory effects
      compared to the organic solvent SPE extracts (in the range of 1.150- 5.144
      mg/mL). The studied honey extracts constitute an interesting source of phenolic
      derivatives that might serve to identify lead compounds, targeting the
      physiologically relevant enzymes CA I and CA II.

PMID- 20687793
TI  - The chemical constituents of Piper kadsura and their cytotoxic and anti
      neuroinflammtaory activities.
AB  - The n-hexane and CHCl3 soluble fractions of the MeOH extract of the aerial parts
      of Piper kadsura were found to potently inhibit nitric oxide (NO) production in
      LPS-activated BV-2 cells, a microglial cell line. From the active fractions, a
      new stereoisomer of guaiane sesquiterpene, 1alpha,5beta-guai-4(15)-ene
      6beta,10beta-diol, kadsuguain A (1) and a new cyclohexadienone, kadsuketanone A
      (2), together with twelve known compounds (3-14) were isolated. The structures of
      these compounds were elucidated by extensive NMR spectral studies. The absolute
      configuration of 2 was determined by circular dichroism (CD) spectra. Compounds
      2, 6, and 11-14 significantly inhibited both nitric oxide (NO) and prostaglandin
      E2 (PGE2) production in the LPS-activated microglia cells. In addition, compounds
      4, 6, and 11-14 exhibited cytotoxicity against the A549, SK-OV-3, SK-MEL-2, and
      HCT15 human tumour cells.

PMID- 20687794
TI  - How the microenvironment shapes chronic lymphocytic leukemia: the cytoskeleton
      connection.
AB  - Chronic lymphocytic leukemia (CLL) is characterized by the accumulation in
      primary and secondary lymphoid tissues of CD5+ B cells that have the same B cell
      receptor (BCR) rearrangement. Genetic alterations and different stimuli
      originating from the microenvironment cooperate in the selection and expansion of
      the malignant clone. Molecular and functional analyses suggest that stimulation
      through the BCR affects the destiny of leukemic cells in terms of life or death.
      Microenvironmental signals are crucial for this process, inducing proliferation
      and leading to the survival and accumulation of leukemic cells within lymphoid
      organs. Nevertheless, a number of major biological issues still remain to be
      solved, including the relationships between cell proliferation and cell
      accumulation within lymphoid organs as well as the mechanisms that regulate CLL
      cell migration and recirculation between peripheral blood and lymphoid tissues.
      We focused on the role played by the cytoskeleton, given its relevance in
      controlling cellular shape, mobility, and homing. We hypothesize that
      hematopoietic cell-specific Lyn substrate 1 (HS1), a putative prognostic marker
      in CLL that interacts with distinct cytoskeleton adapters in leukemic B
      lymphocytes, could regulate the CLL cell cytoskeleton.

PMID- 20687795
TI  - Pharmacologic interception in T-cell leukemia 1A associated pathways as a
      treatment rationale for chronic lymphocytic leukemia.
AB  - Recent therapeutic advances in chronic lymphocytic leukemia (CLL) are reflected
      by high response rates in most subsets of patients. However, refractory disease
      remains a problem, and virtually all of even the most sensitive tumors eventually
      recur. Therefore, ongoing efforts aim at the development of optimized
      interventional designs that more specifically target the strong pro-survival
      signature of the transformed B cell. Stimuli from the CLL microenvironment are
      considered the predominant force that sets this high anti-apoptotic threshold. We
      introduce here our concept that the oncogene T-cell leukemia 1A (TCL1A), which
      induces CLL-like disease in transgenic mice, significantly enhances such milieu
      derived signaling, propagates associated resistance, and therefore represents a
      targetable pathway in CLL. We discuss inhibitory strategies that are based on
      TCL1A's activation of the growth modulating kinase AKT and on influences that
      regulate TCL1A expression. Respective preliminary data indicate that differential
      response categories of CLL exist. Future studies will test TCL1A's inherent
      predictive information.

PMID- 20687796
TI  - Critical role of microRNAs in chronic lymphocytic leukemia: overexpression of the
      oncogene PLAG1 by deregulated miRNAs.
AB  - MicroRNAs (miRNAs) are small, gene encoded RNAs which are able to influence gene
      expression in binding to the 3'UTR of mRNAs. Compared to healthy tissues, the
      global expression of miRNAs in cancerous tissue is frequently down-regulated.
      Likewise in chronic lymphocytic leukemia (CLL), down-regulation of several miRNAs
      has been reported. Analysis of miRNA promoters for epigenetic modifications
      revealed a stronger methylation of down-regulated miRNAs in CLL. To date, several
      target genes affected by deregulated miRNAs have been identified that have impact
      on CLL pathogenesis. The best-described consequence of miRNA deregulation is for
      miRNA-15/16 cluster deletion, which is frequently down-regulated in a subgroup of
      patients with CLL carrying 13q14 deletion. So far, models for miRNA deregulation
      have addressed just single miRNAs. For assessment of complete miRNA deregulation,
      further evaluation of the results from microarray studies is needed. Previously
      we identified the oncogene PLAG1, whose expression is affected by various miRNAs
      deregulated in CLL. The involvement of miRNAs in PLAG1 expression was shown to be
      relevant in pleomorphic adenomas of the salivary gland, too. As PLAG1 is highly
      overexpressed, and its target genes appear to be deregulated in CLL, e.g. BCL-2,
      PLAG1 is a putative new relevant oncogene involved in the pathogenesis of CLL.

PMID- 20687797
TI  - Peripherally inserted central catheter in leukemia: insertion site determines
      clotting risk.

PMID- 20687798
TI  - Toxoplasmosis and allogeneic stem cell transplantation: can we do better?

PMID- 20687799
TI  - Cell cycle characteristics and Epstein-Barr virus are differentially associated
      with aggressive and non-aggressive subsets of Hodgkin lymphoma in pediatric
      patients.
AB  - We investigated the correlation of tumor characteristics with clinico-biological
      markers of aggressive disease, evaluated by Ann Arbor stage, risk group, B
      symptoms, number of involved anatomic areas, mediastinal mass, nodular sclerosis
      (NS) grade, and risk, in pediatric Hodgkin lymphoma (HL). Leukopenia and
      extranodal disease influenced event-free survival (p = 0.032 and p = 0.041). In
      multivariate analysis, extranodal disease was associated with high number of
      tumor-infiltrating eosinophils (p = 0.035) and Ki67 < 50% (p = 0.024); B-symptoms
      with Ki67 > or =75% (p = 0.027) and high LDH levels (p = 0.001); and mediastinal
      mass with leukopenia (p = 0.048), NS grade II (p = 0.025), and high-risk (p =
      0.046). Furthermore, low stages correlated with Ki67 > or =50% (p = 0.005) and
      Epstein-Barr virus (EBV) (p = 0.065). Low-risk NS was associated with EBV (p =
      0.014). Hierarchical cluster analysis identified two clusters, one composed of
      high-risk patients and cell cycle and apoptosis features, and the other including
      low-risk patients, EBV, and low-risk NS. Our results show the association of
      biological markers with disease aggressiveness in pediatric HL.

PMID- 20687801
TI  - Host and nonhost resistance in Medicago-Colletotrichum interactions.
AB  - Medicago truncatula lines resistant (A17) or susceptible (F83005.5) to the
      alfalfa pathogen Colletotrichum trifolii were used to compare defense reactions
      induced upon inoculation with C. trifolii or with the nonadapted pathogens C.
      lindemuthianum and C. higginsianum. Nonadapted Colletotrichum spp. induced a
      hypersensitive response (HR)-like reaction similar to the one induced during the
      host-incompatible interaction. Molecular analyses indicated an induction of PR10
      and chalcone synthase genes in host and nonhost interactions but delayed
      responses were observed in the F83005.5 line. The clste12 penetration-deficient
      C. lindemuthianum mutant induced an HR and defense gene expression, showing that
      perception of nonadapted strains occurs before penetration of epidermal cells.
      Cytological and transcriptomic analyses performed upon inoculation of near
      isogenic M. truncatula lines, differing only at the C. trifolii resistance locus,
      Ct1, with the nonadapted Colletotrichum strain, showed that nonhost responses are
      similar in the two lines. These included a localized oxidative burst,
      accumulation of fluorescent compounds, and transient expression of a small number
      of genes. Host interactions were characterized by a group of defense and
      signaling-related genes induced at 3 days postinoculation, associated with an
      accumulation of salicylic acid. Together, these results show that M. truncatula
      displays a rapid and transient response to nonadapted Colletotrichum strains and
      that this response is not linked to the C. trifolii resistance locus.

PMID- 20687802
TI  - The Ustilago maydis forkhead transcription factor Fox1 is involved in the
      regulation of genes required for the attenuation of plant defenses during
      pathogenic development.
AB  - Ustilago maydis is a plant-pathogenic fungus that establishes a biotrophic
      relationship with its host plant, Zea mays. The pathogenic stage of U. maydis is
      initiated by the fusion of two haploid cells, resulting in the formation of a
      dikaryotic hypha that invades the plant cell. The switch from saprophytic, yeast
      like cells to the biotrophic hyphae requires the complex regulation of a
      multitude of biological processes to constitute the compatible host-fungus
      interaction. Transcriptional regulators involved in the establishment of the
      infectious dikaryon and penetration of the host tissue have been identified;
      however, regulators required during the post-penetration stages remained to be
      elucidated. In this study, we report the identification of a U. maydis forkhead
      transcription factor, Fox1, which is exclusively expressed during biotrophic
      development. Deletion of fox1 results in reduced virulence and impaired tumor
      development. The Deltafox1 hyphae induce the accumulation of H(2)O(2) in and
      around infected cells and a maize defense response phenotypically represented by
      the encasement of proliferating hyphae in a cellulose-containing matrix. The
      phenotype can be attributed to the fox1-dependent deregulation of several
      effector genes that are linked to pathogenic development and host defense
      suppression.

PMID- 20687803
TI  - Age-related resistance of Nicotiana benthamiana against hemibiotrophic pathogen
      Phytophthora infestans requires both ethylene- and salicylic acid-mediated
      signaling pathways.
AB  - Phytophthora infestans, the agent of late blight disease of potato, is a
      hemibiotrophic pathogen with biotrophic action during early infection and
      necrotrophic in the later stage of colonization. Mature Nicotiana benthamiana was
      resistant to P. infestans, whereas relatively young plants were susceptible to
      this pathogen. Young plants became resistant following a pretreatment with
      acibenzolar-S-methyl, a functional analog of salicylic acid (SA), indicating that
      susceptibility of young plants is due to a lack of induction of SA signaling.
      Further analysis with virus-induced gene silencing indicated that NbICS1 and
      NbEIN2, the genes for SA biosynthesis and ethylene (ET) signaling, respectively,
      are required for the resistance of mature N. benthamiana against P. infestans.
      Furthermore, these genes are required for the production of reactive oxygen
      species (ROS) induced by treatment of the INF1 elicitor. In NbICS1-silenced
      plants, cell death induced by either INF1 or necrosis-inducing protein NPP1.1 was
      significantly accelerated. Expression of genes for phytoalexin (capsidiol)
      biosynthesis, NbEAS and NbEAH, were regulated by ET, and gene silencing of either
      of them compromised resistance of N. benthamiana to P. infestans. Together, these
      results suggest that resistance of N. benthamiana against hemibiotrophic P.
      infestans requires both SA-regulated appropriate induction of cell death and ET
      induced production of phytoalexin.

PMID- 20687804
TI  - RBOHF2 of barley is required for normal development of penetration resistance to
      the parasitic fungus Blumeria graminis f. sp. hordei.
AB  - Plant respiratory burst oxidase homologs are prominent sources of reactive oxygen
      species (ROS) in signal transduction and in interaction with microbes. However,
      the function of respiratory burst oxidase homologue (RBOH) genes in interaction
      with microbes might differ for certain plant and pathogen species. We produced
      transgenic barley knock down (KD) for the HvRBOHF2 isoform of NADPH oxidases.
      Young HvRBOHF2 KD shoots did not show obvious morphological alterations from the
      wild type but adult HvRBOHF2 KD plants developed fewer tillers, were less
      fertile, and showed spontaneous cell death in leaf mesophyll. Additionally,
      HvRBOHF2 KD plants were unable to contain wound-induced cell death. Before
      developmental failure became obvious, young HvRBOHF2 KD seedlings were much more
      susceptible to penetration by the biotrophic powdery mildew fungus Blumeria
      graminis f. sp. hordei. Strikingly, the B. graminis f. sp. hordei-induced cell
      wall-associated oxidative burst was not substantially attenuated in HvRBOHF2 KD
      plants but enhanced susceptibility apparently influenced the subcellular site of
      hydrogen peroxide accumulation. Taken together, misexpression of HvRBOHF2 caused
      failure of barley to normally develop penetration resistance to B. graminis f.
      sp. hordei and to control leaf cell death.

PMID- 20687805
TI  - Methyl esterase 1 (StMES1) is required for systemic acquired resistance in
      potato.
AB  - Whether salicylic acid (SA) plays a role in systemic acquired resistance (SAR)
      signaling in potato is currently unclear because potato, unlike tobacco and
      Arabidopsis, contains highly elevated levels of endogenous SA. Recent studies
      have indicated that the SA derivative methyl salicylate (MeSA) serves as a long
      distance phloem-mobile SAR signal in tobacco and Arabidopsis. Once in the distal,
      uninfected tissue of these plant species, MeSA must be converted into
      biologically active SA by the esterase activity of SA-binding protein 2 (SABP2)
      in tobacco or members of the AtMES family in Arabidopsis. In this study, we have
      identified the potato ortholog of tobacco SABP2 (StMES1) and shown that the
      recombinant protein converts MeSA to SA; this MeSA esterase activity is feedback
      inhibited by SA or its synthetic analog, 2, 2, 2, 2'-tetra-fluoroacetophenone
      (tetraFA). Potato plants (cv. Desiree) in which StMES1 activity was suppressed,
      due to either tetraFA treatment or silencing of StMES1 expression, were
      compromised for arachidonic acid (AA)-induced SAR development against
      Phytophthora infestans. Presumably due to the inability of these plants to
      convert MeSA to SA, the SAR-defective phenotype correlated with elevated levels
      of MeSA and reduced expression of pathogenesis-related (PR) genes in the
      untreated distal tissue. Together, these results strongly suggest that SAR
      signaling in potato requires StMES1, its corresponding MeSA esterase activity,
      and MeSA. Furthermore, the similarities between SAR signaling in potato, tobacco,
      and Arabidopsis suggest that at least certain SAR signaling components are
      conserved among plants, regardless of endogenous SA levels.

PMID- 20687806
TI  - Rhodococcus fascians impacts plant development through the dynamic fas-mediated
      production of a cytokinin mix.
AB  - The phytopathogenic actinomycete Rhodococcus fascians D188 relies mainly on the
      linear plasmid-encoded fas operon for its virulence. The bacteria secrete six
      cytokinin bases that synergistically redirect the developmental program of the
      plant to stimulate proliferation of young shoot tissue, thus establishing a leafy
      gall as a niche. A yeast-based cytokinin bioassay combined with cytokinin
      profiling of bacterial mutants revealed that the fas operon is essential for the
      enhanced production of isopentenyladenine, trans-zeatin, cis-zeatin, and the 2
      methylthio derivatives of the zeatins. Cytokinin metabolite data and the
      demonstration of the enzymatic activities of FasD (isopentenyltransferase), FasE
      (cytokinin oxidase/dehydrogenase), and FasF (phosphoribohydrolase) led us to
      propose a pathway for the production of the cytokinin spectrum. Further
      evaluation of the pathogenicity of different fas mutants and of fas gene
      expression and cytokinin signal transduction upon infection implied that the
      secretion of the cytokinin mix is a highly dynamic process, with the consecutive
      production of a tom initiation wave followed by a maintenance flow.

PMID- 20687807
TI  - Transcription of two blue copper-binding protein isogenes is highly correlated
      with arbuscular mycorrhizal development in Medicago truncatula.
AB  - Expression profiling of two paralogous arbuscular mycorrhizal (AM)-specific blue
      copper-binding gene (MtBcp1a and MtBcp1b) isoforms was performed by real-time
      quantitative polymerase chain reaction in wild-type Medicago truncatula Jemalong
      5 (J5) during the mycorrhizal development with Glomus intraradices for up to 7
      weeks. Time-course analysis in J5 showed that expression of both MtBcp1 genes
      increased continuously and correlated strongly with the colonization intensity
      and arbuscule content. MtPT4, selected as a reference gene of the functional
      plant-fungus association, showed a weaker correlation to mycorrhizal development.
      In a second experiment, a range of mycorrhizal mutants of the wild-type J5 was
      assessed. Strictly AM-penetration-defective TRV25-C and TRV25-D (dmi3, Mtsym13),
      hypomycorrhizal TR25 and TR89 (dmi2, Mtsym2) mutants, and a hypermycorrhizal
      mutant TRV17 (sunn, Mtsym12) were compared with J5 3 and 7 weeks after
      inoculation. No MtBcp1 transcripts were detected in the mutants blocked at the
      appressoria stage. Conversely, TR25, TR89, and J5 showed a gradual increase of
      the expression of both MtBcp1 genes in 3- and 7-week-old plants, similar to the
      increase in colonization intensity and arbuscule abundance. The strong
      correlation between the expression level of AM-specific blue copper-binding
      protein-encoding genes and AM colonization may imply a basic role in symbiotic
      functioning for these genes, which may serve as new molecular markers of
      arbuscule development in M. truncatula.

PMID- 20687808
TI  - Effects of galU mutation on Pseudomonas syringae-plant interactions.
AB  - Bacterial galU coding for a uridine diphosphate-glucose pyrophosphorylase plays
      an important role in carbohydrates biosynthesis, including synthesis of
      lipopolysaccharides (LPS), membrane-derived oligosaccharides, and capsular
      polysaccharides. In this study, we characterized the galU mutant of Pseudomonas
      syringae pv. syringae 61 (Psy61), a necrotizing plant pathogen whose
      pathogenicity depends on a functional type III secretion system (T3SS), and
      showed that the Psy61 galU mutant had reduced biofilm formation ability, was
      nonmotile, and had an assembled T3SS structure but failed to elicit
      hypersensitive response in resistant plants and necrotic lesions in susceptible
      plants. Moreover, the defective LPS and other pathogen-associated molecular
      patterns (PAMPs) on the surface of the Psy61 galU mutant were capable of inducing
      PAMP-triggered immunity, which severely compromised the ability of the Psy61 galU
      mutant to survive in planta. Our results demonstrated that the complete LPS
      protected plant-pathogenic bacteria from host innate immunity, similar to what
      was found in animal pathogens, prior to the translocation of T3S effectors and
      bacterial multiplication.

PMID- 20687809
TI  - A competitive index assay identifies several Ralstonia solanacearum type III
      effector mutant strains with reduced fitness in host plants.
AB  - Ralstonia solanacearum, the causal agent of bacterial wilt, is a soil bacterium
      which can naturally infect a wide range of host plants through the root system.
      Pathogenicity relies on a type III secretion system which delivers a large set of
      approximately 75 type III effectors (T3E) into plant cells. On several plants,
      pathogenicity assays based on quantification of wilting symptoms failed to detect
      a significant contribution of R. solanacearum T3E in this process, thus revealing
      the collective effect of T3E in pathogenesis. We developed a mixed infection
      based method with R. solanacearum to monitor bacterial fitness in plant leaf
      tissues as a virulence assay. This accurate and sensitive assay provides evidence
      that growth defects can be detected for T3E mutants: we identified 12 genes
      contributing to bacterial fitness in eggplant leaves and 3 of them were also
      implicated in bacterial fitness on two other hosts, tomato and bean. Contribution
      to fitness of several T3E appears to be host specific, and we show that some
      known avirulence determinants such as popP2 or avrA do provide competitive
      advantages on some susceptible host plants. In addition, this assay revealed that
      the efe gene, which directs the production of ethylene by bacteria in plant
      tissues, and hdfB, involved in the biosynthesis of the secondary metabolite 3
      hydroxy-oxindole, are also required for optimal growth in plant leaf tissues.

PMID- 20687810
TI  - Diversity, distribution, and evolution of Solanum bulbocastanum late blight
      resistance genes.
AB  - Knowledge on the evolution and distribution of late blight resistance genes is
      important for a better understanding of the dynamics of these genes in nature. We
      analyzed the presence and allelic diversity of the late blight resistance genes
      Rpi-blb1, Rpi-blb2, and Rpi-blb3, originating from Solanum bulbocastanum, in a
      set of tuber-bearing Solanum species comprising 196 different taxa. The three
      genes were only present in some Mexican diploid as well as polyploid species
      closely related to S. bulbocastanum. Sequence analysis of the fragments obtained
      from the Rpi-blb1 and Rpi-blb3 genes suggests an evolution through recombinations
      and point mutations. For Rpi-blb2, only sequences identical to the cloned gene
      were found in S. bulbocastanum accessions, suggesting that it has emerged
      recently. The three resistance genes occurred in different combinations and
      frequencies in S. bulbocastanum accessions and their spread is confined to
      Central America. A selected set of genotypes was tested for their response to the
      avirulence effectors IPIO-2, Avr-blb2, and Pi-Avr2, which interact with Rpi-blb1,
      Rpi-blb2, and Rpi-blb3, respectively, as well as by disease assays with a diverse
      set of isolates. Using this approach, some accessions could be identified that
      contain novel, as yet unknown, late blight resistance factors in addition to the
      Rpi-blb1, Rpi-blb2, and Rpi-blb3 genes.

PMID- 20687812
TI  - Abstracts of bone-tec 2009, International Bone-Tissue-Engineering Congress.
      October 8-11, 2009. Hannover, Germany.

PMID- 20687811
TI  - BAX INHIBITOR-1 is required for full susceptibility of barley to powdery mildew.
AB  - BAX INHIBITOR-1 (BI-1) is one of the few proteins known to have cross-kingdom
      conserved functions in negative control of programmed cell death. Additionally,
      barley BI-1 (HvBI-1) suppresses defense responses and basal resistance to the
      powdery mildew fungus Blumeria graminis f. sp. hordei and enhances resistance to
      cell death-provoking fungi when overexpressed in barley. Downregulation of HvBI-1
      by transient-induced gene silencing or virus-induced gene silencing limited
      susceptibility to B. graminis f. sp. hordei, suggesting that HvBI-1 is a
      susceptibility factor toward powdery mildew. Transient silencing of BI-1 did not
      limit supersusceptibility induced by overexpression of MLO. Transgenic barley
      plants harboring an HvBI-1 RNA interference (RNAi) construct displayed lower
      levels of HvBI-1 transcripts and were less susceptible to powdery mildew than
      wild-type plants. At the cellular level, HvBI-1 RNAi plants had enhanced
      resistance to penetration by B. graminis f. sp. hordei. These data support a
      function of BI-1 in modulating cell-wall-associated defense and in establishing
      full compatibility of B. graminis f. sp. hordei with barley.

PMID- 20687813
TI  - Effect of micro- and macroporosity of bone tissue three-dimensional-poly(epsilon
      caprolactone) scaffold on human mesenchymal stem cells invasion, proliferation,
      and differentiation in vitro.
AB  - The design of porous scaffolds able to promote and guide cell proliferation,
      colonization, and biosynthesis in three dimensions is key determinant in bone
      tissue engineering (bTE). The aim of this study was to assess the role of the
      micro-architecture of poly(epsilon-caprolactone) scaffolds in affecting human
      mesenchymal stem cells' (hMSCs) spatial organization, proliferation, and
      osteogenic differentiation in vitro. Poly(epsilon-caprolactone) scaffolds for bTE
      and characterized by mono-modal and bi-modal pore size distributions were
      prepared by the combination of gas foaming and selective polymer extraction from
      co-continuous blends. The topological properties of the pore structure of the
      scaffolds were analyzed and the results correlated with the ability of hMSCs to
      proliferate, infiltrate, and differentiate in vitro in three dimensions. Results
      showed that the micro-architecture of the pore structure of the scaffolds plays a
      crucial role in defining cell seeding efficiency as well as hMSCs' three
      dimensional colonization, proliferation, and osteogenic differentiation. Taken
      all together, our results indicated that process technologies able to allow a
      fine-tune of the topological properties of biodegradable porous scaffolds are
      essential for bTE strategies.

PMID- 20687814
TI  - SILS and NOTES cholecystectomy: a tailored approach.
AB  - BACKGROUND: Natural orifice transluminal endoscopic surgery (NOTES) and single
      incision laparoscopic surgery (SILS) have been proposed as different solutions to
      further minimize the invasiveness of laparoscopy. In this article, we present our
      experience with NOTES and SILS over the last few years, trying to focus on
      identifying which technique should be offered to which patients at the beginning
      of 2010. PATIENTS AND METHODS: Between January 2009 and January 2010, 100
      patients were diagnosed with symptomatic cholelithiasis at our department.
      Considering our positive previous experiences with NOTES and SILS, we offered the
      hybrid NOTES approach to women over 40 years with no previous pelvic surgery or
      history of inflammatory pelvic disease and SILS to male patients and women
      excluded from the hybrid NOTES approach, with previous surgery in the upper right
      quadrant and gallbladder empyema being the main contraindications. RESULTS:
      Twenty-six patients accepted the SILS or NOTES approach instead of standard
      laparoscopic cholecystectomy (LC). Seventy-four patients underwent standard LC
      via four trocars. In the hybrid NOTES transvaginal cholecystectomy, there were no
      problems or complications related to the culdotomy, trocar, or stay suture
      placement. There were no conversions, and all the procedures were performed as
      planned without complications. In the SILS cholecystectomy, there were no
      problems or complications related to the trocar or stay sutures placement. All
      the procedure were completed without complications. CONCLUSIONS: NOTES and SILS
      are promising techniques that need new, dedicated instrumentations to reduce
      technical limitations. Randomized studies comparing SILS/NOTES and traditional
      laparoscopy are necessary to evaluate safety, efficacy, and potential benefits.

PMID- 20687815
TI  - Laparoscopic treatment for small intestinal bleeding: a report of 77 cases.
AB  - BACKGROUND: Morbidity of small intestinal disease is rare and the associated
      lesion is hard to be detected due to lack of specific manifestations and
      effective diagnostic approaches. Hematochezia and melena are the most common
      symptoms in small intestinal diseases. Hence, small intestinal disease is an
      important differential diagnosis when hematochezia or melena occurs, especially
      when gastric and colonic diseases are excluded. As the small intestinal lesion is
      hard to be located preoperatively, laparotomy used to be performed without a
      preoperative location. This might lead to related postoperative complications.
      With the development of laparoscopic technique, laparoscopic operations are more
      frequently applied to surgical disease, despite their benign or malignant nature.
      Generally, almost all kinds of small intestinal disease can be treated with
      laparoscopic surgery. METHODS: Clinical data of 77 patients with small intestinal
      bleeding undergoing laparoscopic or laparoscopy-assisted operations from April
      2003 to December 2008 were included, and their clinical information were analyzed
      retrospectively. RESULTS: No intraoperative complication or conversion was
      observed in all cases. The mean operative time, mean estimated blood loss, and
      mean size of incision were 78.3 +/- 30.5 minutes, 17.5 +/- 9.8 mL, and 3.3 +/-
      1.9 cm, respectively. Postoperative complications occurred in 4 patients,
      including 2 cases of adhesive ileus, 1 case of gastric retention, and 1 case of
      anastomotic bleeding. All of them were cured by nonoperative management. The mean
      flatus time was 2 days after operation and the mean postoperative hospital stay
      was 7 days. There was 1 case of gastrointestinal stromal tumor with local
      recurrence and hepatic metastasis. Four patients died from metastasis of
      malignant tumors during the follow-up from 2 to 70 months after operations. No
      trocar site or wound recurrences were noted. CONCLUSIONS: Laparoscopic treatment
      in small intestinal bleeding is feasible, safe, and minimally invasive. It may be
      widely used in the future for its good therapeutic outcomes and improved
      diagnostic chance in small intestinal bleeding diseases.

PMID- 20687816
TI  - Emergency laparoscopic surgery for right colonic diseases with peritonitis.
AB  - BACKGROUND: Laparoscopic bowel resection for right colonic diseases with
      peritonitis is technically difficult and time-consuming, particularly in the
      presence of hard adhesion and dense inflammation. Moreover, peritonitis
      frequently leads to an emergency operation. Therefore, we evaluated the
      feasibility and effectiveness of emergency laparoscopic bowel resection in
      patients with these diseases. METHODS: During 3 years (November 2006 to October
      2009), we enrolled 31 consecutive patients who underwent an emergency
      laparoscopic bowel resection for right colonic disease with peritonitis. In 2
      patients, perforated malignancy was suspected preoperatively, but there was no
      patient with malignancy at pathologic finding. We analyzed the clinical outcomes,
      including complications. RESULTS: The mean operating time was 140 minutes, and
      the mean hospital stay was 10 days. There was 1 conversion (3%), and the other
      intraoperative procedures were uneventful. Four complications (13%) occurred
      after treatment (1 intra-abdominal abscess, 2 wound abscesses, and 1 adhesive
      ileus). The intra-abdominal abscess was treated by subsequent percutaneous
      drainage; the wound abscesses were treated conservatively. One patient with an
      adhesive ileus 12 months after treatment was managed with a bowel resection.
      After a median follow-up of 16 months, the other patients had no complications.
      CONCLUSIONS: Emergency laparoscopic bowel resection may be a feasible, effective
      method for the treatment of right colonic diseases with peritonitis.

PMID- 20687817
TI  - Increasing the realism of a laparoscopic box trainer: a simple, inexpensive
      method.
AB  - BACKGROUND AND PURPOSE: Simulation-based training in medical education is
      increasing. Realism is an integral element of creating an engaging, effective
      training environment. Although physical trainers offer a low-cost alternative to
      expensive virtual reality (VR) simulators, many lack in realism. The aim of this
      research was to enhance the realism of a laparoscopic box trainer by using a
      simple, inexpensive method. MATERIALS AND METHODS: Digital images of the
      abdominal cavity were captured from a VR simulator. The images were printed onto
      a laminated card that lined the bottom and sides of the box-trainer cavity. The
      standard black neoprene material that encloses the abdominal cavity was replaced
      with a skin-colored silicon model. RESULTS AND CONCLUSIONS: The realism of the
      modified box trainer was assessed by surgeons, using quantitative and qualitative
      methodologies. Results suggest that the modified box trainer was more realistic
      than a standard box trainer alone. Incorporating this technique in the training
      of laparoscopic skills is an inexpensive means of emulating surgical reality that
      may enhance the engagement of the learner in simulation.

PMID- 20687818
TI  - Palmar staining following methylene blue leak test during laparoscopic Roux-en-Y
      gastric bypass.
AB  - A morbidly obese female with a body mass index of 39 and without a past medical
      history of skin or connective tissue disorders was taken to the operating room
      for a laparoscopic Roux-en-Y gastric bypass, utilizing the methylene blue leak
      test. On the following day, she developed significant blancheable bluish skin
      discoloration on her bilateral fingers and palms without sensory changes. The
      rest of her postoperative course was otherwise uneventful. In this article, we
      describe an unusual dermatologic change related to the use of methylene blue
      during bariatric surgery.

PMID- 20687819
TI  - Nonoperative closure of persistent gastrocutaneous fistulas in children with 2
      octylcyanoacrylate.
AB  - A persistent gastrocutaneous fistula (pGCF) is an all-too-common complication
      following removal of a gastrostomy tube (GT) in a child and is associated with
      significant morbidity. The most common initial methods to manage pGCF include
      local would care and occlusion techniques. Failure of this approach is followed
      by surgical excision of the fistula tract and closure of the gastrostomy under
      general anesthesia. We report the first use of a tissue adhesive, 2
      octylcyanoacrylate (2OC) (Dermabond; Ethicon, Sommerville, NJ) as a non-surgical
      method to close pGCF in children. METHODS: The families of children presenting to
      the pediatric surgical division for management of a pGCF were offered the option
      of 2OC closure. Children not receiving or who failed to achieve closure with 2OC
      therapy underwent surgery for excision of the pGCF with primary closure of the
      stomach and soft tissues. RESULTS: Seven children underwent 2OC therapy. 57% (4
      of 7) of the children had complete closure of the pGCF with 2OC therapy. Three
      children underwent operative closure without complication. CONCLUSIONS: The
      tissue adhesive 2OC can successfully close a pGCF in children after GT removal.
      This therapy is cost-effective, non-invasive, does not require general
      anesthesia, and can be performed in an outpatient setting.

PMID- 20687820
TI  - A middle fidelity model is effective in teaching and retaining skill set needed
      to perform a laparoscopic pyloromyotomy.
AB  - INTRODUCTION: An inanimate technical skills trainer for laparoscopic
      pyloromyotomy (LP) has not been described. A middle fidelity model, reproducing
      the three consistent steps in LP, was developed as a component of a teaching
      module for surgical residents, and tested on medical students, residents, and
      pediatric surgeons. MATERIALS AND METHODS: In the first phase of the study, a
      cohort of 29 pediatric surgeons used the LP model and completed questionnaires
      about the model's realism and accuracy. Descriptive statistics were used to
      analyze questionnaire responses. Chi-square tests were performed to determine if
      level of experience influenced responses. For the second phase of the study,
      medical students and surgical residents individually participated in the training
      of cognitive knowledge about hypertrophic pyloric stenosis and skills acquisition
      for LP. Subject testing consisted of simulator task performance and multiple
      choice quiz administration immediately after training and repeated at 8 weeks
      after training. Data were analyzed by using paired sample t-tests and one-way
      analyses of variance (ANOVA). RESULTS: The pediatric surgeons agreed that the
      model accurately simulated essential components of the pyloromyotomy, and that
      the model would be an excellent tool to introduce surgeons to LP. A total of 26
      students and early surgical residents completed the training and testing.
      Knowledge-based test performance improved from pre- to postinstruction by 17.45
      [standard error of the mean (SEM) + 3.5] (P < 0.001) and from preinstruction to 8
      weeks by 4.54 (SEM = 3.2) (P = 0.17). Mean improvement in time of simulator task
      performance was 85.2 +/- 75.4 seconds. Based on a one-way ANOVA, higher level of
      training was associated with decreased mean times (P = 0.04). CONCLUSIONS: Face
      and content validities of the simulation were demonstrated by the pediatric
      surgeons. An effective training experience was demonstrated with medical students
      and residents. At 2 months, simulator task-completion rates and task-performance
      times showed technical skills were retained, whereas, based on test scores,
      cognitive knowledge was not as well retained.

PMID- 20687821
TI  - Introduction to special section on evidence-based practices for persons with
      intellectual and developmental disabilities.

PMID- 20687822
TI  - Twenty years of communication intervention research with individuals who have
      severe intellectual and developmental disabilities.
AB  - This literature review was conducted to evaluate the current state of evidence
      supporting communication interventions for individuals with severe intellectual
      and developmental disabilities. We reviewed 116 articles published between 1987
      and 2007 in refereed journals meeting three criteria: (a) described a
      communication intervention, (b) involved one or more participants with severe
      intellectual and developmental disabilities, and (c) addressed one or more areas
      of communication performance. Many researchers failed to report treatment
      fidelity or to assess basic aspects of intervention effects, including
      generalization, maintenance, and social validity. The evidence reviewed indicates
      that 96% of the studies reported positive changes in some aspects of
      communication. These findings support the provision of communication intervention
      to persons with severe intellectual and developmental disabilities. Gaps in the
      research were reported as were recommendations for future research.

PMID- 20687823
TI  - Using participant data to extend the evidence base for intensive behavioral
      intervention for children with autism.
AB  - We gathered individual participant data from 16 group design studies on
      behavioral intervention for children with autism. In these studies, 309 children
      received behavioral intervention, 39 received comparison interventions, and 105
      were in a control group. More children who underwent behavioral intervention
      achieved reliable change in IQ (29.8%) compared with 2.6% and 8.7% for comparison
      and control groups, respectively, and reliable change in adaptive behavior was
      achieved for 20.6% versus 5.7% and 5.1%, respectively. These results equated to a
      number needed to treat of 5 for IQ and 7 for adaptive behavior and absolute risk
      reduction of 23% and 16%, respectively. Within the behavioral intervention
      sample, IQ and adaptive behavior at intake predicted gains in adaptive behavior.
      Intensity of intervention predicted gains in both IQ and adaptive behavior.

PMID- 20687824
TI  - Caring, employment, and quality of life: comparison of employed and nonemployed
      mothers of adults with intellectual disability.
AB  - The effects of caregiving on mothers of adults with intellectual disability was
      examined by determining whether there are differences in quality of life and
      related factors between mothers with different employment status. Study
      participants were 302 working-age mothers who had adult children with
      intellectual disability based on the 2008 census survey on intellectual
      disability carried out in Hsinchu, City, Taiwan. Results revealed that
      nonemployed mothers are more likely to have a lower level of health status,
      including the WHOQOL Physical Health domain, than are mothers employed fulltime.
      Multiple regression analysis showed that mothers' quality of life was
      significantly determined by the availability of a person with whom they could
      share care work, family income, social support, and employment status.

PMID- 20687825
TI  - Use of special education services among children with and without congenital
      gastrointestinal anomalies.
AB  - Our objective was to evaluate the relationship between congenital
      gastrointestinal anomalies requiring neonatal surgery and neurodevelopmental
      outcome. Among the children born in metropolitan Atlanta during 1982-2001 who
      survived to age 1 year (N = 762,824), we identified children with congenital
      gastrointestinal anomalies via linkage with the Metropolitan Atlanta Congenital
      Defects Program and children who received special education services via linkage
      with the Special Education Database of Metropolitan Atlanta. Several modest
      increases in special education service use were observed among children with
      isolated congenital gastrointestinal anomalies; no association was statistically
      significant. Among children with Hirschsprung disease, gastroschisis, esophageal
      atresia, intestinal malrotation, bowel atresia, or imperforate anus who had
      multiple anomalies, we observed statistically significant increases in special
      education service use.

PMID- 20687828
TI  - Quantifying dysphonia severity using a spectral/cepstral-based acoustic index:
      Comparisons with auditory-perceptual judgements from the CAPE-V.
AB  - This study investigated the relationship between acoustic spectral/cepstral
      measures and listener severity ratings in normal and disordered voice samples.
      CAPE-V sentence samples and the vowel /a/were elicited from eight normal speakers
      and 24 patients with varying degrees of dysphonia severity. Samples were analysed
      for measures of the cepstral peak prominence (CPP), the ratio of low-to-high
      spectral energy, and their respective standard deviations. Perceptual ratings of
      overall severity were also obtained for all samples. Results showed that all
      acoustic variables combined in a four-factor model which correlated with
      perceived severity with R = 0.81 (R(2) = 0.65). For the vowel /a/, a five-factor
      model incorporating all acoustic variables and gender correlated with perceived
      severity with R = 0.96 (R(2) = 0.91). Results indicate that a strong relationship
      between perceptual and acoustic estimates of dysphonia severity can be achieved
      in both continuous speech and vowel contexts using a model incorporating
      spectral/cepstral measures.

PMID- 20687826
TI  - Side effects of minocycline treatment in patients with fragile X syndrome and
      exploration of outcome measures.
AB  - Minocycline can rescue the dendritic spine and synaptic structural abnormalities
      in the fragile X knock-out mouse. This is a review and preliminary survey to
      document side effects and potential outcome measures for minocycline use in the
      treatment of individuals with fragile X syndrome. We surveyed 50 patients with
      fragile X syndrome who received minocycline for at least 2 weeks and found that
      the most common reported side effect is gastrointestinal difficulty, including
      loss of appetite. The families reported an improvement in language and behavioral
      areas. Outcome measures in the design of future randomized clinical trials should
      include both behavioral and language measures. As with any other treatments, we
      emphasize that randomized clinical trials are needed to determine the efficacy of
      minocycline in fragile X syndrome.

PMID- 20687829
TI  - The cocoon of the fossorial frog Cyclorana australis functions primarily as a
      barrier to water exchange with the substrate.
AB  - Studies of evaporative water loss using streams of dry air in the laboratory have
      demonstrated reduced rates in various taxa of cocooned frogs. However, because
      the cocoon is formed in subterranean burrows with humid microclimates and no air
      flow, loss of water by evaporation is likely to be negligible. In contrast,
      although potentially important, the influence of the cocoon on water exchange
      with the soil surface has not been characterized. In dry soils, there is a
      sizable water potential gradient between the frog and the soil; hence, we
      hypothesized that cocoons would play a role in reducing liquid water loss to dry
      substrates. Individuals of the burrowing frog Cyclorana australis (Hylidae:
      Pelodryadinae) were induced to form cocoons in the laboratory. On semisolid agar
      solute substrates across a range of water potentials, the hygroscopic cocoon
      absorbed small but similar amounts of moisture. With the cocoon removed, the
      frogs gained or lost water, depending on the direction of the frog-substrate
      water potential difference. Plasma osmolality of cocooned frogs was significantly
      higher than in hydrated frogs. Because cocooned frogs did not exchange
      significant amounts of water at either high (wet) or low (dry) substrate water
      potentials, we conclude that the cocoon of fossorial frogs acts as a physical
      barrier that breaks the continuity between frog and substrate. We contend that
      the primary function of the cocoon is to prevent liquid water loss to drying clay
      and loam soils, rather than to prevent subterranean evaporative water loss.

PMID- 20687830
TI  - Functional plasticity of the developing cardiovascular system: examples from
      different vertebrates.
AB  - Technical advances that have made it possible to perform physiological
      measurements on very small organisms, including those in embryonic and larval
      stages, have resulted in the formation of the discipline of developmental
      physiology. The transparency and size of developing organisms in some areas
      permit insights into physiological processes that cannot be obtained with opaque,
      adult organisms. On the other hand, it is widely accepted that without eggs,
      there are no chickens, so physiological adaptations during early life are just as
      important to species survival as those manifested by adults. Physiological
      adaptations of early developmental stages, however, are not always the same as
      patterns known in adults; they often follow their own rules. The adaptability of
      early developmental stages demonstrates that development is not stereotyped and a
      phenotype is not just the result of genetic information and the expression of a
      certain series of genes. Environmental factors influence phenotype production,
      and this in turn results in flexibility and plasticity in physiological
      processes. This article comprises exemplary studies presented at the Fourth
      International Conference in Africa for Comparative Physiology and Biochemistry
      (Maasai Mara, Kenya, 2008). It includes a brief introduction into technical
      advances, discusses the developing cardiovascular system of various vertebrates,
      and demonstrates the flexibility and plasticity of early developmental stages.
      Fluid forces, oxygen availability, ionic homeostasis, and the chemical
      environment (including, e.g., hormone concentrations or cholesterol levels) all
      contribute to the shaping and performance of the cardiovascular system.

PMID- 20687831
TI  - The strigolactone story.
AB  - Strigolactones (SLs) were originally isolated from plant root exudates as
      germination stimulants for root parasitic plants of the family Orobanchaceae,
      including witchweeds (Striga spp.), broomrapes (Orobanche and Phelipanche spp.),
      and Alectra spp., and so were regarded as detrimental to the producing plants.
      Their role as indispensable chemical signals for root colonization by symbiotic
      arbuscular mycorrhizal fungi was subsequently unveiled, and SLs then became
      recognized as beneficial plant metabolites. In addition to these functions in the
      rhizosphere, it has been recently shown that SLs or their metabolites are a novel
      class of plant hormones that inhibit shoot branching. Furthermore, SLs are
      suggested to have other biological functions in rhizosphere communications and in
      plant growth and development.

PMID- 20687833
TI  - Engineering pathogen resistance in crop plants: current trends and future
      prospects.
AB  - Transgenic crops are now grown commercially in 25 countries worldwide. Although
      pathogens represent major constraints for the growth of many crops, only a tiny
      proportion of these transgenic crops carry disease resistance traits.
      Nevertheless, transgenic disease-resistant plants represent approximately 10% of
      the total number of approved field trials in North America, a proportion that has
      remained constant for 15 years. In this review, we explore the socioeconomic and
      biological reasons for the paradox that although technically useful solutions now
      exist for providing transgenic disease resistance, very few new crops have been
      introduced to the global market. For bacteria and fungi, the majority of
      transgenic crops in trials express antimicrobial proteins. For viruses, three
      quarters of the transgenics express coat protein (CP) genes. There is a notable
      trend toward more biologically sophisticated solutions involving components of
      signal transduction pathways regulating plant defenses. For viruses, RNA
      interference is increasingly being used.

PMID- 20687834
TI  - Studying plant-pathogen interactions in the genomics era: beyond molecular Koch's
      postulates to systems biology.
AB  - Molecular factors enabling microbial pathogens to cause plant diseases have been
      sought with increasing efficacy over three research eras that successively
      introduced the tools of disease physiology, single-gene molecular genetics, and
      genomics. From this work emerged a unified model of the interactions of
      biotrophic and hemibiotrophic pathogens, which posits that successful pathogens
      typically defeat two levels of plant defense by translocating cytoplasmic
      effectors that suppress the first defense (surface arrayed against microbial
      signatures) while evading the second defense (internally arrayed against
      effectors). As is predicted from this model and confirmed by sequence pattern
      driven discovery of large repertoires of cytoplasmic effectors in the genomes of
      many pathogens, the coevolution of (hemi)biotrophic pathogens and their hosts has
      generated pathosystems featuring extreme complexity and apparent robustness.
      These findings highlight the need for a fourth research era of systems biology in
      which virulence factors are studied as pathosystem components, and pathosystems
      are studied for their emergent properties.

PMID- 20687832
TI  - Role of small RNAs in host-microbe interactions.
AB  - Plant defense responses against pathogens are mediated by activation and
      repression of a large array of genes. Host endogenous small RNAs are essential in
      this gene expression reprogramming process. Here, we discuss recent findings on
      pathogen-regulated host microRNAs (miRNAs) and small interfering RNAs (siRNAs)
      and their roles in plant-microbe interaction. We further introduce small RNA
      pathway components, including Dicer-like proteins (DCLs), double-stranded RNA
      (dsRNA) binding protein, RNA-dependent RNA polymerases (RDRs), small RNA
      methyltransferase HEN1, and Argonaute (AGO) proteins, that contribute to plant
      immune responses. The strategies that pathogens have evolved to suppress host
      small RNA pathways are also discussed. Collectively, host small RNAs and RNA
      silencing machinery constitute a critical layer of defense in regulating the
      interaction of pathogens with plants.

PMID- 20687835
TI  - Recurrence after treatment for pulmonary multidrug-resistant tuberculosis.
AB  - We estimated the proportion of recurrence within 2 years among adults cured by
      individualized multidrug-resistant tuberculosis regimens in Peru. Among 310
      individuals with at least 24 months of follow-up, 16 experienced an episode of
      recurrent tuberculosis. If we assume the worst for treatment effectiveness-that
      all 16 episodes were caused by the original tuberculosis strain-then 5.2% (95%
      confidence interval, 3.0%-8.2%) experienced true relapse. This is an upper-bound
      estimate of relapse on which new regimens must improve.

PMID- 20687836
TI  - Brill-Zinsser disease in a patient following infection with sylvatic epidemic
      typhus associated with flying squirrels.
AB  - Recrudescent Rickettsia prowazekii infection, also known as Brill-Zinsser
      disease, can manifest decades after untreated primary infection but is rare in
      contemporary settings. We report the first known case of Brill-Zinsser disease in
      a patient originally infected with a zoonotic strain of R. prowazekii acquired
      from flying squirrels.

PMID- 20687837
TI  - Arterolane, a new synthetic trioxolane for treatment of uncomplicated Plasmodium
      falciparum malaria: a phase II, multicenter, randomized, dose-finding clinical
      trial.
AB  - BACKGROUND: Drug-resistant Plasmodium falciparum malaria necessitates development
      of novel drugs for treatment.The present study assessed the efficacy and safety
      of 3 dose levels of arterolane (RBx 11160), a synthetic trioxolane, for treatment
      of acute uncomplicated falciparum malaria. METHODS: In this randomized, double
      blind, multicenter, parallel-group, dose-finding, phase II trial, 230 patients
      from 4 centers in Thailand, India, and Tanzania (mainland and Zanzibar) received
      either 50 mg (n=78), 100mg (n=76), or 200 mg (n=76) of arterolane once daily for
      7 days. Patients (aged 13-65 years) with asexual parasite density of 1000-100,000
      parasites/microL were included and were followed up for 28 days. The median time
      to 90% parasite clearance (PC90) was evaluated. RESULTS: The median PC90 was
      longer in the group receiving the 50-mg dose (19.4 h), compared with the groups
      receiving the 100-mg dose (12.8 h) and 200-mg dose (12.6 h) (P < .01). The
      polymerase chain reaction-corrected adequate clinical and parasitological
      responses on day 28 were 63%, 71%, and 72% for the groups receiving the 50-mg,
      100-mg, and 200-mg doses, respectively, by intention-to-treat analysis (odds
      ratio, 1.55; 95%confidence interval, 0.78-3.06, for comparison of the 200-mg and
      50-mg dose groups). Treatment was generally well tolerated. No patient died or
      experienced any serious adverse event. Mild complaints were reported in <10%of
      the patients and were similar in the 3 groups. Biochemistry and hematological
      analyses did not show any signof drug toxicity in any patient. CONCLUSION:
      Arterolane at daily doses of 100 and 200 mg is a rapidly acting, effective, and
      safe synthetic antimalarial drug, which may potentially represent an alternative
      to artemisinin derivatives in antimalarial combination therapy. TRIAL
      REGISTRATION: ClinicalTrials.gov identifier NCT00362050.

PMID- 20687838
TI  - AS03(A)-Adjuvanted influenza A (H1N1) 2009 vaccine for adults up to 85 years of
      age.
AB  - BACKGROUND: Vaccination of high-risk groups was started shortly after the
      emergence of the influenza A (H1N1)2009 pandemic virus. METHODS: Healthy adults
      were enrolled into 2 age strata: 18-60 years and 160 years, and received
      monovalent influenza vaccine containing 3.75 microg of A/California/2009 (H1N1)
      hemagglutinin antigen, adjuvanted with AS03A. Hemagglutination inhibition assay
      based antibody titers against H1N1 vaccine were assessed after 1 vaccine
      dose(primary endpoint), after which subjects were randomized 1:1 to receive no
      further vaccination or a second dose.Immunogenicity endpoints were European
      licensure criteria for influenza vaccines. Exploratory analyses assessed the
      effect of previous seasonal influenza vaccination on responses to the H1N1
      vaccine. RESULTS: Licensure criteria for immunogenicity were fulfilled after 1
      dose of H1N1 vaccine (N=240). For subjects 18-60 years of age, previous
      vaccination against seasonal influenza within the preceding 2 seasons resulted in
      significantly lower geometric mean titers (adjusted for baseline antibody titer)
      after 1 or 2 doses of H1N1 vaccine (P <.001 and P=.003, respectively). Transient
      mild or moderate injection-site pain was reported by 87.5%and 65.0% of subjects
      18-60 years of age and >60 years of age, respectively, after the first dose, and
      in 63% of subjects overall after the second dose. CONCLUSIONS: A single dose of
      3.75 microg hemagglutinin antigen, AS03A-adjuvanted H1N1 2009 vaccine was
      immunogenic and well tolerated in adults. In exploratory analyses (of subjects 18
      60 years of age), postvaccination antibody titers were lower in subjects who had
      previously received seasonal influenza vaccination, compared with those who had
      not. This phenomenon warrants further investigation. CLINICAL TRIALS
      REGISTRATION: NCT00968526.

PMID- 20687839
TI  - Not all patients with vancomycin-resistant enterococci need to be isolated.
AB  - BACKGROUND: Vancomycin-resistant enterococci (VRE) have triggered multiple
      outbreaks. However, VRE of genotype vanC appear not to be associated with
      outbreaks. The goal of this study was to estimate the risk of bloodstream
      infections in patients colonized with VRE of genotype vanC who received care from
      a bone marrow transplant unit for patients with leukemia, where only standard
      precautions were implemented for VRE of genotype vanC during the last 9 years.
      METHODS: Since 2000, all patients in the bone marrow transplant unit underwent
      routine VRE rectal screening, data were prospectively entered in a database, and
      isolates were molecularly characterized. Infection control policy required
      contact isolation for patients infected with VRE of genotype vanA or vanB but
      only standard precautions for patients infected with VRE of genotype vanC.
      RESULTS: From January 2000 to July 2008, 290 isolates of VRE of genotype vanC
      obtained from 273 different patients were identified, with an incidence of 25-43
      isolates/year. Of 290 isolates, 285 (98%) were identified in rectal screening
      swabs, 5 were from other body sites, and none required specific treatment. During
      the entire study period, only 1 case of bloodstream infection was detected,
      reflecting an incidence of 1 (0.4%) of the 273 patients, or <0.2 cases per 1000
      patient-days. No outbreaks were recorded. CONCLUSIONS: These data provide strong
      evidence that carriers of VRE of genotype vanC do not require contact isolation,
      thereby saving resources and potentially improving patient care. The genotype
      should be routinely determined in areas with a high prevalence of VRE of genotype
      vanC.

PMID- 20687840
TI  - Novel Treponema pallidum serologic tests: a paradigm shift in syphilis screening
      for the 21st century.
AB  - The mainstay of diagnosis for Treponema pallidum infections is based on
      nontreponemal and treponemal serologic tests. Many new diagnostic methods for
      syphilis have been developed, using specific treponemal antigens and novel
      formats, including rapid point-of-care tests, enzyme immunoassays, and
      chemiluminescence assays. Although most of these newer tests are not yet cleared
      for use in the United States by the Food and Drug Administration, their
      performance and ease of automation have promoted their application for syphilis
      screening. Both sensitive and specific, new screening tests detect antitreponemal
      IgM and IgG antibodies by use of wild-type or recombinant T. pallidum antigens.
      However, these tests cannot distinguish between recent and remote or treated
      versus untreated infections. In addition, the screening tests require
      confirmation with nontreponemal tests. This use of treponemal tests for screening
      and nontreponemal serologic tests as confirmatory tests is a reversal of long
      held practice. Clinicians need to understand the science behind these tests to
      use them properly in syphilis management.

PMID- 20687841
TI  - Remission of severe CD8(+) cytotoxic T cell skin infiltrative disease in human
      immunodeficiency virus-infected patients receiving highly active antiretroviral
      therapy.
AB  - BACKGROUND: A CD8 cutaneous lymphoinfiltrative disease has been described in
      human immunodeficiency virus (HIV)-infected patients presenting with a severe
      erythroderma. The true nature of this severe skin infiltrative disorder is still
      elusive. Although some clinical features of this syndrome have raised the
      hypothesis of its malignant nature in initial observations, several studies have
      provided stronger support to the hypothesis that it is a reactive pseudotumoral
      process. METHODS: From 1995 through 2008, 8 HIV type 1 (HIV-1)-infected patients
      presenting with a chronic skin eruption, diagnosed as CD8 T cell infiltration of
      the skin, were studied. RESULTS: All patients showed diffuse infiltrated skin
      with superficial lymphadenopathy. A profound CD4(+) lymphocytopenia and
      eosinophilia were other major features. Histological and immunostaining analysis
      revealed a predominant dermal and epidermal infiltration by CD8(+) T cells
      belonging to the cytotoxic lineage, without evidence for a monoclonal status by
      polymerase chain reaction-based molecular analysis of lesional skin. A remission
      of skin symptoms occurred in all cases following highly active antiretroviral
      therapy, which paralleled the decrease of HIV-1 RNA load and the increase of
      CD4(+) peripheral blood absolute count. CONCLUSIONS: Altogether, these results
      emphasize the reactive, nonmalignant nature of this syndrome and strongly support
      the coupling between HIV-induced immune deficiency and uncontrolled CD8
      activation.

PMID- 20687842
TI  - The complexity, relative value, and financial worth of curbside consultations in
      an academic infectious diseases unit.
AB  - BACKGROUND: Curbside consultations are common in clinical practice. The
      complexity, relative value, and revenue loss associated with curbside
      consultations are not well defined. METHODS: Curbside consultations performed
      during a 1-year period were studied. Each curbside consultation was assigned a
      Current Procedural Terminology (CPT) code on the basis of the inpatient versus
      outpatient status of the patient, initial versus subsequent care, and clinical
      complexity. On the basis of the CPT code, the physician work component of the
      relative value unit (wRVU) was assigned for each curbside consultation. The 2005
      Centers for Medicaid and Medicare Services conversion factor of $37.89 per wRVU
      was used for cost estimates. Comparisons were made with formal consultations
      performed during the same time period. RESULTS: A total of 1001 curbside
      consultations were fielded: 66% involved outpatients, and 97% were coded as
      initial consultations. A total of 78% of curbside consultations were considered
      complex in nature, being assigned a CPT code of level 4-5, including 84% of the
      inpatient and 75% of the outpatient curbside consultations. These curbside
      consultations would have generated 2480 wRVUs. During the same period, formal
      consultations generated 12,121 wRVUs. Thus, curbside consultations represented
      17% (2480/14,601) of the clinical work value of the infectious diseases unit. If
      the infectious diseases unit had performed these curbside consultations as formal
      consultations, an additional $93,979 in revenue would have been generated.
      CONCLUSIONS: Curbside consultations are common and complex. The curbside
      consultation should be incorporated into measures of infectious diseases
      providers' productivity and compensation.

PMID- 20687843
TI  - Recent advances into understanding some aspects of the structure and function of
      mammalian and avian lungs.
AB  - Recent findings are reported about certain aspects of the structure and function
      of the mammalian and avian lungs that include (a) the architecture of the air
      capillaries (ACs) and the blood capillaries (BCs); (b) the pulmonary blood
      capillary circulatory dynamics; (c) the adaptive molecular, cellular,
      biochemical, compositional, and developmental characteristics of the surfactant
      system; (d) the mechanisms of the translocation of fine and ultrafine particles
      across the airway epithelial barrier; and (e) the particle-cell interactions in
      the pulmonary airways. In the lung of the Muscovy duck Cairina moschata, at
      least, the ACs are rotund structures that are interconnected by narrow
      cylindrical sections, while the BCs comprise segments that are almost as long as
      they are wide. In contrast to the mammalian pulmonary BCs, which are highly
      compliant, those of birds practically behave like rigid tubes. Diving pressure
      has been a very powerful directional selection force that has influenced
      phenotypic changes in surfactant composition and function in lungs of marine
      mammals. After nanosized particulates are deposited on the respiratory tract of
      healthy human subjects, some reach organs such as the brain with potentially
      serious health implications. Finally, in the mammalian lung, dendritic cells of
      the pulmonary airways are powerful agents in engulfing deposited particles, and
      in birds, macrophages and erythrocytes are ardent phagocytizing cellular agents.
      The morphology of the lung that allows it to perform different functions
      including gas exchange, ventilation of the lung by being compliant, defense, and
      secretion of important pharmacological factors-is reflected in its "compromise
      design."

PMID- 20687844
TI  - Energetics of lizard embryos at fluctuating temperatures.
AB  - Most animals experience fluctuations in temperature during development, but
      studies of energetics have ignored the potential influence of these thermal
      fluctuations. We measured the energetics of Sceloporus undulatus lizard embryos
      under two conditions that differ realistically in the mean and variance of
      temperature (diel cycles of 20 degrees -30 degrees and 20 degrees -34 degrees C).
      Our goal was to determine whether embryos in warm nests would expend more energy
      to develop than embryos in cool nests. We quantified metabolic rates during
      development, durations of incubation, and sizes at hatching. To describe changes
      in metabolic rate during incubation, we used the Akaike Information Criterion to
      determine the best statistical model among a set of six candidates. Once the best
      model was determined, the energetic cost of development was estimated by
      integrating metabolic rates over the period of incubation. We found that some
      form of sigmoidal model provided the best fit to the data for the majority of
      embryos (75%). Although embryos in the warmer treatment hatched earlier, the cost
      of development ( approximately 1.6 kJ) did not differ significantly between
      embryos in the two treatments. This estimate of energy expenditure at fluctuating
      temperatures accords with previous estimates of energy expenditure at constant
      temperatures, suggesting that embryonic metabolism under realistic thermal
      conditions does not differ substantially from that under constant conditions.

PMID- 20687845
TI  - Effect of a new moisturizing lotion on immediate and cumulative skin hydration:
      Two randomized, intra-individual, vehicle- and comparator-controlled studies.
AB  - Moisturizers increase skin hydration and can serve as adjunctive care in
      dermatologic conditions such as xerosis, psoriasis vulgaris, atopic dermatitis
      and ichthyosis, in which dry skin is implicated. A non-irritating hydrating
      lotion (CDA lotion) was recently developed. We assessed the effect of CDA lotion
      on skin hydration in two randomized, evaluator-blind and intra-individual
      comparison studies. After a single application, CDA lotion induced significantly
      greater hydration than the non-treated control for at least 24 hours (p < 0.001).
      After 4 days of twice-daily application, compared with the non-treated control,
      CDA lotion induced significantly greater skin hydration up to 3 days after
      treatment cessation (p < 0.05) and significant improvement in the clinical skin
      dryness score up to 7 days after treatment cessation (p < 0.05). The immediate
      and cumulative hydration effects of CDA lotion were also compared to those of
      several currently available moisturizing products. In summary, application of CDA
      lotion increases skin hydration and alleviates the condition of skin dryness.

PMID- 20687846
TI  - Pustulosis palmoplantaris is a disease distinct from psoriasis.
AB  - Pustulosis palmoplantaris (PPP) is a chronic inflammatory skin disease with a
      considerable impairment of quality of life and is characterized by sterile
      pustules and red, scaly skin on the palms and soles. The position of PPP in
      relation to psoriasis is unclear. Some authors regard PPP as a distinct disease
      entity, whereas others categorize PPP as a manifestation of psoriasis. Related to
      this discussion is the question on the treatment of PPP. Should the treatment of
      PPP follow the guidelines for psoriasis or is it a disease that has to be treated
      in a different way? The purpose of this editorial is to review the differences
      between PPP and psoriasis and to understand these differences with respect to the
      pathogenesis and treatment.

PMID- 20687847
TI  - Laparoscopy-assisted distal gastrectomy combined with laparoscopic spleen
      preserving distal pancreatectomy for the treatment of early gastric cancer with
      pancreatic cystic neoplasm.
AB  - The use of laparoscopy-assisted distal gastrectomy (LADG) for early gastric
      cancer (EGC) and laparoscopic distal pancreatectomy (LDP) for lesions of benign
      or borderline malignancy have gained worldwide acceptance because they are viewed
      as safe and feasible. A 59-year-old man was diagnosed with EGC and intraductal
      papillary mucinous neoplasm (IPMN) simultaneously during cancer screening. LDP
      was performed prior to LADG due to the possibility of splenectomy. After
      completing LDP, LADG was performed in the usual manner. LADG combined with spleen
      preserving LDP was performed safely. The operating time was 561 minutes, and
      there was no intraoperative complication. The patient was discharged on
      postoperative 10 without any complications. No recurrence or distant metastasis
      occurred during the subsequent 40 months. LADG combined with spleen-preserving
      LDP for EGC and IPMN was found to be feasible and less invasive than open
      surgery.

PMID- 20687849
TI  - Laparoscopic anterior y-v pyeloplasty: a valuable treatment option in patients
      with small or intrarenal pelvis.
AB  - The aim of the study was to describe the technique of modified laparoscopic Foley
      Y-V pyeloplasty-anterior Y-V plasty and the results of the operation in the
      authors' material. In the modified operation, a V-shaped flap is created from the
      anterior wall of the renal pelvis. Thus two lines of sutures are located on the
      anterior, easily accessible wall of the renal pelvis. Thirty-six patients were
      operated on using this technique from May 2005 to January 2009. One patient did
      not turn up for the follow-up. Complete success was observed in 34 of 35 patients
      (97.1%). The mean follow-up time was 24 (4-43) months. The mean operative time
      was 160 minutes. We did not observe any serious complications in the
      postoperative period. Our results seem to indicate that the anterior Y-V plasty
      may constitute a reasonable treatment option for patients with small or
      intrarenal pelvis and no dorsally crossing vessels.

PMID- 20687848
TI  - Fetal immune activation to malaria antigens enhances susceptibility to in vitro
      HIV infection in cord blood mononuclear cells.
AB  - Mother-to-child-transmission (MTCT) of human immunodeficiency virus (HIV) remains
      a significant cause of new HIV infections in many countries. To examine whether
      fetal immune activation as a consequence of prenatal exposure to parasitic
      antigens increases the risk of MTCT, cord blood mononuclear cells (CBMCs) from
      Kenyan and North American newborns were examined for relative susceptibility to
      HIV infection in vitro. Kenyan CBMCs were 3-fold more likely to be infected with
      HIV than were North American CBMCs (P=.03). Kenyan CBMCs with recall responses to
      malaria antigens demonstrated enhanced susceptibility to HIV when compared with
      Kenyan CBMCs lacking recall responses to malaria (P=.03). CD4(+) T cells from
      malaria-sensitized newborns expressed higher levels of CD25 and human leukocyte
      antigen DR ex vivo, which is consistent with increased immune activation. CD4(+)
      T cells were the primary reservoir of infection at day 4 after virus exposure.
      Thus, prenatal exposure and in utero priming to malaria may increase the risk of
      MTCT.

PMID- 20687850
TI  - Gastrotomy closure with the lock-it system and the Padlock-G clip: a survival
      study in a porcine model.
AB  - BACKGROUND AND STUDY AIMS: The success of natural orifice surgery depends on
      secure closure of the transmural gut opening, so a rapid, secure, and easy-to
      place closure method is desirable. Our aim was to determine whether a gastrotomy
      can be closed safely and effectively from within the stomach in a survival model
      by using a novel, endoscopically placed device: the Padlock-G system. PATIENTS
      AND METHODS: This was a pilot study of 4 survival animals in an animal laboratory
      setting. Gastrotomies were made in the stomachs of laboratory swine, and the
      abdomen was explored by using a standard gastroscope. Gastrotomies were then
      closed by using the Padlock-G system. Survival for 2 or 6 weeks was the primary
      outcome measurement. Secondary outcomes included ease of use, visual assessment
      of closure integrity immediately and at necropsy, presence of adhesions, evidence
      of infection, and histologic appearance at the closure sites. RESULTS: All
      animals thrived, ate normally, and gained weight. None developed fever,
      tachycardia, or signs of peritoneal irritation. Closure-site inspection at
      necropsy revealed excellent healing, with epithelial growth over the Padlock-G.
      There were no ulcers, serosal surfaces were tightly closed, and no defects could
      be seen. There were no signs of peritoneal inflammation, intra-abdominal
      adhesions, or gastric spillage. Histologic evaluation showed organizing
      granulation tissue with fibrosis, vascular proliferation, and mild chronic
      inflammatory infiltrate (i.e., scar). CONCLUSIONS: The Padlock-G is easy to
      place, provides a durable closure, and allows survival animals to thrive without
      adverse sequellae. This device provides a suitable closure system for
      transgastric NOTES.

PMID- 20687851
TI  - Simultaneous laparoscopic resection of primary colorectal cancer and metastatic
      liver tumor: initial experience of single institute.
AB  - BACKGROUND: Approximately 20%-25% of patients with colorectal cancer have
      synchronous liver metastasis at the time of diagnosis. Simultaneous resection of
      primary colorectal cancer and metastatic liver tumor is the treatment option in
      colorectal cancer with liver metastasis. The aim of this study was to report our
      initial experiences of simultaneous laparoscopic resection of colorectal cancer
      and liver metastasis. METHODS: A single-center, retrospective study of 10 cases
      of laparoscopic simultaneous resection of colorectal cancer and liver metastasis
      was carried out. RESULTS: The patients' average age was 63.7 years (range, 48-75
      years) and average body mass index was 23.5 kg/m2(range, 20-27.4 kg/m2). The
      primary cancer was right-sided colon cancer in 4 cases, left-sided colon cancer
      in 3 cases, and rectal cancer in 3 cases. Single-lesion liver metastasis was
      found in 6 cases and two or more lesion liver metastasis was found in 4 cases.
      The mean operating time was 401 minutes (range, 230-620 minutes) and blood loss
      was 500 mL (range, 60-1000 mL). The mean hospital stay was 10 days (range, 7-15
      days). One case was converted to open surgery and anastomotic leakage was
      encountered in the converted case. CONCLUSIONS: This study shows that
      simultaneous laparoscopic resection of primary colorectal cancer and liver
      metastasis is safe and technically feasible in selected patients.

PMID- 20687852
TI  - Laparoendoscopic single-site surgery using a 2-mm miniport: initial gynecologic
      experience performed by a standard trocar and instruments.
AB  - OBJECTIVES: To evaluate the feasibility, safety, and patients' satisfaction of
      laparoendoscopic single-site surgery (LESS) with a 2-mm miniport using a standard
      trocar and instruments. METHODS: Between November 2008 and October 2009, we
      performed LESS for benign gynecologic conditions with a 2-mm miniport in 61
      patients. Only 1 case was converted to conventional laparoscopic surgery using
      three ports to perform an appendectomy. The level of satisfaction of the patients
      was surveyed with five scales ("very satisfied," "satisfied," "not sure,"
      "unsatisfied," and "very unsatisfied"). RESULTS: The mean operative time was 46.6
      +/- 20.7 minutes, and the mean blood loss was 8.9 +/- 7.4 mL. The length of the
      hospital stay postoperatively averaged 1.8 +/- 0.9 days. No complications that
      required treatment occurred. Among 60 patients, 52 patients (87%) responded to
      the survey. Thirteen patients (25%) were "very satisfied," 29 patients (56%) were
      "satisfied," 8 patients (15%) were "not sure," and 2 patients (4%) were
      "unsatisfied." Forty-two patients (81%) had a positive perception of the surgery.
      Forty-nine patients (94%) responded that they were satisfied with the cosmetic
      outcome. CONCLUSION: LESS with a 2-mm miniport is a feasible and safe treatment
      modality for benign gynecologic diseases without incurring additional costs.
      Moreover, the cosmetic results were excellent.

PMID- 20687853
TI  - The cold knife: a new laparoscopic instrument for ureteropelvic junction
      incision.
AB  - OBJECTIVE: The use of laparoscopic scissors or blades in laparoscopic
      nondismembered pyeloplasty is quite common; however, the incision made using
      these tools may cause difficulties for the surgeon. We developed an efficient,
      safe, reusable, and inexpensive instrument to incise the pelvis and ureter during
      laparoscopic pyeloplasty. The aim of the present study was to evaluate the new
      laparoscopic instrument designed for pelvic and ureteric incisions. MATERIALS AND
      METHODS: The cold knife consists of an internal urethrotome that is transformed
      into an endoscopic instrument that can be inserted easily through a 5-mm-diameter
      trocar. It has a manual retraction system that enables a stand-by position for
      added protection when no incisions are being made. The new tool was trialed in
      laparoscopic Y-V pyeloplasty. Data regarding perioperative parameters and
      outcomes were collected and analyzed. RESULTS: Eight patients participated in the
      present study. All patients underwent Y-V pyeloplasty using a three-port
      retroperitoneal access. Mean operative time was 166.2 minutes (range: 100-300).
      There were no complications during the procedures. CONCLUSIONS: Laparoscopic cold
      knife for laparoscopic pyeloplasty is a simple, safe, reusable, and inexpensive
      instrument with a low maintenance cost.

PMID- 20687854
TI  - Current status of en bloc stapling of the renal hilum during laparoscopic
      nephrectomy.
AB  - INTRODUCTION: Increasing literature has been published lately addressing the
      safety and efficacy of en bloc stapling of the renal hilum during laparoscopic
      nephrectomy and nephroureterectomy. The aim of this review was to analyze the
      available literature on en bloc stapling of the renal hilum and to complement it
      with technical issues that are required, according to our vast experience in en
      bloc and separate stapling, to safely control the hilum with this technique.
      MATERIALS AND METHODS: A PubMed search using the terms "en bloc," "nephrectomy,"
      and "laparoscopy" was conducted. We identified seven publications that have
      looked into hilar stapling technique. RESULTS: Seven publications were found,
      which included a total of 434 patients who underwent en bloc stapling of the
      renal hilum. No complications specifically ascribable to this type of hilar
      control were encountered. No cases of postoperative arteriovenous fistula have
      been reported. CONCLUSIONS: En bloc stapling has become an established method to
      secure the renal hilum during laparoscopic nephrectomy and laparoscopic
      nephroureterectomy. Although no cases of postoperative arteriovenous fistula
      formation have been reported with the use of modern titanium staplers, longer
      follow-up is necessary to ascertain that it does not occur in the late
      postoperative period. We believe that well-trained laparoscopic surgeons should
      master this technique in both emergency and elective situations.

PMID- 20687855
TI  - A simple way to mesh insertion during transabdominal preperitoneal laparoscopic
      inguinal hernia repair.

PMID- 20687856
TI  - Laparoscopic training in urology: critical analysis of current evidence.
AB  - AIM: To provide an evidence-based analysis on the status and perspectives of
      laparoscopic training in urologic surgery. METHODS: A thorough review of the
      current literature was performed as of January 31, 2009, using the Medline
      database through a PubMed search. The search protocol included a free-text query
      using the following terms: "training," "urologic laparoscopy," "urology," and
      "laparoscopy." Suitable articles were selected on the basis of the study content.
      The following issues were addressed: prediction of laparoscopic skills and
      transfer of training in clinical practice; homemade and commercially available
      laparoscopic trainers and simulators; training models for specific laparoscopic
      procedures; mentored training programs; formal training programs; and the impact
      of robotics in laparoscopic training. RESULTS: Currently available tools
      predicting laparoscopic skills lack adequate validation to justify their
      widespread adoption. There still is not enough evidence to show definite transfer
      of skills from currently available simulators to the operating theater. Learning
      opportunities continue to evolve. Specific models have been developed for complex
      procedures. Various informal training programs exist, yet most urologists will
      not be able to complete a formal fellowship. Postgraduate urologists may possibly
      be more rapidly and efficiently trained using a structured mentoring program.
      Robotics is likely to have an increasing role in teaching urological laparoscopy.
      CONCLUSIONS: Despite progress in recent years and an extensive amount of data
      from the urological literature, the ideal training program in urological
      laparoscopy remains a goal to be determined objectively.

PMID- 20687857
TI  - Minimally invasive management of postoperative bleeding after radical
      prostatectomy: transarterial embolization.
AB  - BACKGROUND AND PURPOSE: Severe postoperative bleeding after radical prostatectomy
      is a rare, but serious, complication. Massive postoperative bleeding causing
      hemodynamic instability necessitates open surgical exploration and can be
      associated with considerable morbidity. We report our experience with minimally
      invasive management of postprostatectomy hemorrhage via transarterial
      embolization (TAE). PATIENTS AND METHODS: From July 2006 to April 2009, men with
      severe immediate postoperative bleeding that caused hemodynamic instability after
      radical prostatectomy were enrolled. We performed emergency angiography and
      superselective TAE instead of surgical exploration as the initial management. TAE
      was performed using an enbucrilate:ethiodized poppy seed oil 1:3 mixture. We
      determined treatment success rate, efficacy, and safety. RESULTS: A total of 4
      among 563 (0.7%) patients had postoperative bleeding that fit the inclusion
      criteria in this period. CT angiography revealed active bleeding in all cases.
      All patients were successfully treated with TAE without any additional treatment,
      such as surgical exploration, and there was no treatment-related adverse event.
      Three (75%) patients regained continence within 6 months. Two (50%) patients were
      potent at 12-month follow-up. CONCLUSION: During a 3-year period, we successfully
      treated all patients who had severe immediate postoperative bleeding after
      radical prostatectomy with TAE. We concluded that rapid diagnosis by CT
      angiography and early TAE could replace surgical exploration in this situation.
      In addition, this could minimize the morbidity associated with severe bleeding,
      transfusion, and open surgical exploration.

PMID- 20687858
TI  - Totally ultrasound versus fluoroscopically guided complete supine percutaneous
      nephrolithotripsy: a first report.
AB  - PURPOSE: As endourologists are highly exposed to X-ray irradiation during
      endourologic surgeries, the use of alternative methods for entrance into the
      collective system and dilatation of tract could be safe and less expensive.
      MATERIALS AND METHODS: Percutaneous access was created under ultrasonographic
      guidance in the complete supine position without flank elevation in 14 patients
      (group A) and under fluoroscopic guidance in the complete supine position without
      flank elevation in 14 patients (group B). We performed all steps of the complete
      supine percutaneous nephrolithotripsy (PCNL) with ultrasonographic guidance in
      group A. RESULTS: In group A, mean age of patients was 46.5 +/- 15.54 years and
      in group B 45.21 +/- 10.72 years. The mean stone burden was 51.07 and 41.92 mm in
      groups A and B, respectively (p = 0.54). Mean operative time in group A was 88.93
      +/- 33.29 minutes and in group B it was 79.29 +/- 16.74 minutes (p = 0.34). Stone
      free rate was 78.6% in group A and 71.4% in group B (p = 0.66). Hospital stay was
      85.88 +/- 17.25 and 80.20 +/- 17.71 hours in groups A and B, respectively (p =
      0.12). Transfusion was done in 1 (7.14%) patient in group A and in 3 (21.43%)
      patients in group B (p = 0.28). Fever was detected in 2 (14.28%) patients in
      group A and in 1 (7.14%) patient in group B (p = 0.54). In our study, there were
      no pleural effusion, postoperative hematoma, renal pelvis perforation, and
      visceral organ trauma in any groups. CONCLUSION: We showed that totally
      ultrasound-guided complete supine PCNL is safe and feasible even in reoperative
      patients. It has certain advantages such as elimination of X-ray exposure to the
      surgeon and staff of the operating room, avoidance of contrast material
      administration, identification of all the tissue between the skin and kidney, and
      the energy expenditure of the surgeon and other staff of the operating room is
      decreased as it is not necessary to wear a lead shield.

PMID- 20687859
TI  - Geographical range of Rio Mamore virus (family Bunyaviridae, genus Hantavirus) in
      association with the small-eared pygmy rice rat (Oligoryzomys microtis).
AB  - Hantavirus HTN.007 was originally isolated from a small-eared pygmy rice rat
      (Oligoryzomys microtis) captured in northeastern Peru. The results of analyses of
      nucleotide and amino acid sequence data in this study indicated that HTN.007 is a
      strain of Rio Mamore virus (RIOMV) which is enzootic in small-eared pygmy rice
      rat populations in Bolivia. As such, the results of this study extend our
      knowledge of the geographical range of RIOMV and support the notion that the
      small-eared pygmy rice rat is the principal host of RIOMV.

PMID- 20687860
TI  - Primary causes of death in reported cases of fatal West Nile Fever, United
      States, 2002-2006.
AB  - Morbidity and mortality associated with human West Nile virus (WNV) infection is
      generally attributable to severe neurologic disease; most illness with WNV,
      however, is characterized by febrile illness. Although generally considered to be
      a benign, self-limited syndrome, some cases of West Nile Fever (WNF) have been
      reported as resulting in fatal outcome. We reviewed cause-of-death information
      for 35 cases of WNF reported as fatal to the Centers for Disease Control and
      Prevention between 2002 and 2006, to determine underlying primary causes of death
      and identify groups at highest risk for fatal WNF. Fifteen were determined to be
      misclassified neuroinvasive disease cases; one death was medically unrelated to
      WNV infection. Among the remaining 23 cases, the median age was 78 years (range:
      54-92), and 78% were >70 years old; the median age for all 13,482 reported cases
      of WNF during this time period was 47 years (range: 1 month-97 years). Cardiac (8
      cases, 35%) and pulmonary complications (6 cases, 25%) were the most common
      primary causes of death. Underlying medical conditions among fatal WNF cases
      included cardiovascular disease (13; 76%), hypertension (8; 47%), and diabetes
      mellitus (6; 35%). Our study suggests that in some individuals, especially
      persons of advanced age and those with underlying medical conditions, WNF may
      precipitate death. The elderly are at increased risk of death from both West Nile
      neuroinvasive disease and WNF, which emphasizes the importance of primary
      prevention of WNV infection and close monitoring for cardiac and pulmonary
      complications in elderly patients hospitalized for WNV disease.

PMID- 20687862
TI  - The pediatric diabetes consortium: improving care of children with type 1
      diabetes through collaborative research.
AB  - Although there are some interactions between the major pediatric diabetes
      programs in the United States, there has been no formal, independent structure
      for collaboration, the sharing of information, and the development of joint
      research projects that utilize common outcome measures. To fill this unmet
      clinical and research need, a consortium of seven pediatric diabetes centers in
      the United States has formed the Pediatric Diabetes Consortium (PDC) through an
      unrestricted grant from Novo Nordisk, Inc. (Princeton, NJ). This article
      describes the organizational structure of the PDC and the design of a study of
      important clinical outcomes in children and adolescents with new-onset, type 1
      diabetes mellitus (T1DM). The outcomes study will describe the changes in A1c
      levels, the frequency of adverse events (diabetic ketoacidosis/severe
      hypoglycemia), and the frequency and timing of the "honeymoon" phase in newly
      diagnosed patients with T1DM over the first 12-24 months of the disease and
      examine the relationship between these clinical outcomes and demographic,
      socioeconomic, and treatment factors. This project will also allow the Consortium
      to develop a cohort of youth with T1DM whose clinical course has been well
      characterized and who wish to participate in future clinical trials and/or
      contribute to a repository of biological samples.

PMID- 20687863
TI  - Basal insulin substitution with glargine or continuous subcutaneous insulin
      infusion in adult type 1 diabetes patients-a randomized controlled trial.
AB  - BACKGROUND: It is generally held that basal insulin substitution with continuous
      subcutaneous insulin infusion (CSII) provides less variable glucose levels than
      with long-acting insulin analogs, e.g., glargine, in patients with type 1
      diabetes, although this has not been convincingly demonstrated by continuous
      glucose monitoring. METHODS: To compare glucose control assessed by a continuous
      glucose monitoring system (CGMS) during basal insulin substitution with glargine
      versus CSII, we conducted a non-blinded, randomized, crossover trial in 15 type 1
      diabetes patients experienced with CSII. All subjects were randomly assigned to
      receive either a morning dose of insulin glargine, comprising their average 24-h
      basal insulin requirement, minus 2.4 U, which was delivered by the pump, or to
      continue as before for 4 weeks followed by a 1-week washout period and a
      crossover. All mealtime doses of insulin were given by the pump as before. CGMS
      data were blinded until the end of the study. RESULTS: The mean blood glucose was
      lower in the non-glargine arm according to self-monitoring of plasma glucose (9.2
      vs. 10.6 mmol/L; P = 0.010) and CGMS (9.1 vs. 10.3 mmol/L; P = 0.002), and
      hemoglobin A1c was 6.5% without glargine versus 6.8% with (P = 0.018). There were
      no significant differences in glucose variability measured as SD of plasma
      glucose (SDPG) or mean amplitude of glycemic excursions (MAGE), although
      significantly longer periods of glucose values spent within the target of 4.5
      10.0 mmol/L were demonstrated in the non-glargine arm using CGMS (P = 0.034).
      More episodes below 3.5 mmol/L were seen during the CSII period (P = 0.053).
      CONCLUSIONS: CSII provided improved glucose control compared to glargine with a
      lower mean plasma glucose and longer periods of glucose values within target on a
      somewhat lower insulin dose. There was a tendency with more episodes below 3.5
      mmol/L during CSII. No difference with respect to glucose variability was found
      when calculated as SDPG or MAGE.

PMID- 20687864
TI  - Dermanyssus gallinae infestation: an unusual cause of scalp pruritus treated with
      permethrin shampoo.
AB  - Dermanyssus gallinae is a blood parasite of wild birds, but it is also a pest in
      the poultry industry. It occasionally bites mammals and thus rarely creates skin
      problems such as itching, papules, vesicles, and dermatitis. A 92-year-old man
      presented with severe itch on his head, particularly at night. He had been
      misdiagnosed with senile pruritus and treated with antihistamines and topical
      corticosteroids with temporary relief of the symptoms. On the basis of clinical
      and parasitological findings, D. gallinae dermatitis was diagnosed.
      Decontamination of the patient's immediate environment was not helpful. The
      patient was successfully treated using a 1% permethrin shampoo once a week for 2
      weeks. During 3 months of follow-up he was free of symptoms. The case is of
      significance because most dermatologists have difficulty identifying
      ectoparasitoses, such as those that arise within new or atypical conditions.

PMID- 20687865
TI  - The prevalence of self-monitoring of blood glucose and costs of glucometer strips
      in a nationwide cohort.
AB  - OBJECTIVE: This study used nationwide data to determine the prevalence of self
      monitoring of blood glucose (SMBG) among all non-institutionalized persons living
      in Norway and to estimate the prevalence of SMBG among diabetes patients, the
      frequency and cost of SMBG, and the use of different glucometers. METHODS: This
      retrospective, descriptive study is based on data of sales of glucometer strips
      to non-institutionalized persons in Norway in 2008. The data included gender, age
      group, month of purchase, sales place, type of strips, number of packages
      dispensed, and cost of strips. Additionally, statistics on sales of insulin and
      oral antidiabetes medications were obtained from the Norwegian Prescription
      Database. RESULTS: A total of 96,999 persons purchased strips, a prevalence of
      2%. Approximately 70% of diabetes patients practiced SMBG. An average patient
      used 1.7 strips per day, and younger patients purchased more strips than older
      patients. Fewer than 50% of patients performed glucose measurements daily. One
      percent of patients used more than 10 strips daily and was accountable for 8% of
      total costs. Most patients used only one type of strips, but the number of strips
      purchased increased with the number of different strips. The average annual cost
      of strips was 446 euro per person. CONCLUSIONS: Two percent of all non
      institutionalized inhabitants and an estimated 70% of patients using diabetes
      medication purchased SMBG strips. A small percentage of the patients incurred a
      substantial proportion of the costs. This, along with the fact that over half of
      the patients monitor less than once per day, calls for tighter follow-up of
      diabetes patients.

PMID- 20687866
TI  - Diabetic ketoacidosis caused by exposure of insulin to low temperature.

PMID- 20687867
TI  - Glycemic variability in inadequately controlled type 1 diabetes and type 2
      diabetes on intensive insulin therapy: a cross-sectional, observational study.
AB  - BACKGROUND: Glycemic variability is suggested to be a predictor for the risk of
      complications of diabetes. A multitude of parameters to express glycemic
      variability have been described, but no gold standard exists. The easy measurable
      parameter SD has been shown to be strongly related to other parameters in a group
      of patients with mostly well-controlled type 1 and type 2 diabetes mellitus (T1DM
      and T2DM, respectively). Glycemic variability is higher in T1DM compared with
      T2DM in mixed populations with different treatments, but studies in patients on
      intensive insulin treatment are lacking. Therefore in this study we investigate
      different parameters of glycemic variability and differences between T1DM and
      T2DM in inadequately controlled patients on intensive insulin treatment. METHODS:
      In this cross-sectional, observational study we describe glycemic variability,
      measured as SD, coefficient of variation, continuous overall net glycemic action,
      and mean of daily differences in a cohort of inadequately controlled T1DM (n =
      166) and T2DM (n = 58) patients on intensive insulin treatment. RESULTS: SD of 48
      h (SD(total)) was highly correlated to all other measured parameters of glycemic
      variability (r = 0.66-0.88). All parameters of glycemic variability were
      significantly higher in T1DM compared to T2DM (P < 0.001), although hemoglobin
      A1c and mean glucose were comparable and treatment regimen was the same. In the
      cohort of T2DM patients but not T1DM, a longer duration of insulin therapy was
      associated with higher glycemic variability. CONCLUSIONS: SD(total) is a
      conveniently measurable parameter to express glycemic variability in patients
      with inadequate control with intensive insulin therapy. Patients with T1DM and
      long-lasting T2DM have the highest glycemic variability.

PMID- 20687868
TI  - A device to measure heat flow through the skin in people with diabetes.
AB  - INTRODUCTION: As people age, and especially for older people with diabetes, there
      is increased susceptibility to burns. However, this is not true for all older
      people or all people with diabetes. The factors that predict burn susceptibility
      in specific members of the population with diabetes have not been elucidated. To
      understand the heat transfer properties of the skin in different parts of the
      body and how it is altered by skin blood flow, age, and glycemic control, a new
      device was developed. METHODS: The device was a Plexiglas (Arkema, Colombes,
      France) capsule (thermode) that has a footprint on the skin of 20 cm(2), with the
      side contacting the skin made of thin brass. The thermode was machined to allow
      the free flow of water through the interior with the exception of a small hole
      for a laser Doppler flow meter to assess blood flow under the capsule. Flow
      directors kept the water flow even on the under surface of the capsule and
      minimized turbulent flow until high water flow rates are forced through the
      capsule. RESULTS: When tested, the device provided even heat on the brass surface
      and could show the movement of heat into the skin and the corresponding changes
      in skin blood flow and temperature. In limited testing, clear differences were
      seen in heat flux in people with diabetes versus controls. CONCLUSION: This
      device might be very useful in determining the early onset of diabetes-related
      skin damage. Future studies should include examining different regions of the
      body and variables such as hemoglobin A1c.

PMID- 20687869
TI  - Scope of information communications technology in the health of diabetes patients
      in poor rural zones of panama through holistic, interactive, and persuasive model
      to facilitate self-care of diabetes patients.
AB  - BACKGROUND: In Latin America, public health systems that manage and warrant the
      health of the population lack mechanisms and technological capabilities that
      enable them to accept and adopt initiatives focused to guide, look after, and
      improve the quality of life of millions of patients with diabetes who need
      attention and special care. However, the proposal presented here for a holistic,
      interactive, and persuasive model to facilitate self-care of diabetes patients
      (hiPAPD) is the first proposal in Panama, Central America, and the Caribbean
      Region to develop and implement information communications technology (ICT)
      platforms for the care of patients with chronic diseases such as diabetes.
      METHODS: The process of experimentation was initiated with an agreement with all
      the staff of the project to comply with the international biomedical studies
      stipulations, having as reference the Declaration of Helsinki of the World
      Medical Association (Recommendations to Guide to Doctors in Biomedical Research
      on People). RESULTS: After several months of evaluation and ongoing work the
      study obtained successful validation of the hiPAPD model. The project had the
      support of 107 patients with diabetes, their families, friends, doctors, nurses
      and nursing assistants, and social groups in rural communities. Finally, the
      project contributed to society with a highly innovative ICT environment that
      facilitates self-care of diabetes patients without financial resources and
      health. CONCLUSIONS: A timely health treatment at a decisive moment may be the
      difference in care for patients. Through the validation process conducted in this
      research initiative, it was demonstrated that the hiPAPD model, from the
      perspective of the patient with diabetes, relatives, friends, health workforce
      (nurses and nursing assistants), doctors, and societal contexts, allowed the
      improvement of the quality of life of patients with diabetes in poor rural zones
      of Panama.

PMID- 20687870
TI  - Therapeutic potential of peptide motifs--Part IV.

PMID- 20687871
TI  - Mitochondria-targeted antioxidant peptides.
AB  - Overproduction of reactive oxygen species (ROS) under pathophysiologic conditions
      is part of the disease process. These ROS are released from different sources,
      and in particular from mitochondria. Although the molecular mechanisms
      responsible for mitochondria-mediated disease processes are unclear, oxidative
      stress seems to play an important role. ROS are essential to cell function, but
      adequate levels of antioxidant defenses are required in order to avoid the
      harmful effects that excessive ROS production can produce. Mitochondrial
      oxidative stress damage and dysfunction contribute to a number of cell
      pathologies that manifest themselves through a range of conditions. The
      antioxidants available until now have not proved to be particularly effective
      against many of these disorders. It is possible that these antioxidants do not
      reach the sites of free radical generation, especially when mitochondria are the
      primary source of ROS. Recent developments in mitochondria-targeted antioxidants
      have moved closer to providing protection against mitochondrial oxidative damage.
      The SS (Szeto-Schiller) peptide antioxidants represent a novel approach that
      employs the targeted delivery of antioxidants to the inner mitochondrial
      membrane. These SS peptides scavenge hydrogen peroxide and peroxynitrite and
      inhibit lipid peroxidation. By reducing mitochondrial ROS, they inhibit
      mitochondrial permeability transition and cytochrome c release, thus preventing
      oxidant-induced cell death. Preclinical studies support the use of these peptides
      for ischemia-reperfusion injury and neurodegenerative disorders. Although
      peptides have often been considered to be poor drug candidates, the few that have
      been studied are promising agents for the treatment of diseases.

PMID- 20687872
TI  - Peptidomimetic competitive inhibitors of protein tyrosine phosphatases.
AB  - This review discusses the development of the active site-directed protein
      tyrosine phosphatase (PTP) inhibitors based on peptides and some closely related
      nonpeptidic scaffolds. A straightforward approach is to substitute various
      nonhydrolyzable analogs for the phosphotyrosine (pTyr) of optimal or
      physiological phosphopeptide substrates of PTPs. The advances in small molecule
      peptidic PTP inhibitors and their nonpeptidic derivatives have been greatly aided
      by X-ray crystallographic and NMR spectrometric studies. Given the importance of
      PTPs in disease-associated signal transduction and the continuing progress in PTP
      drug discovery, some clinically useful PTP inhibitors may emerge in the near
      future.

PMID- 20687873
TI  - Epitope discovery and their use in peptide based vaccines.
AB  - With recent advances in the design and delivery of peptide-based therapeutics
      there has been a growing interest on the use of peptides in vaccine design.
      Moreover, functional dissection and proteomic analysis of the immunogenic
      epitopes of proteins from pathogenic micro-organisms, cancers and self-tissues
      targeted by autoimmune responses, have broadened the range of target epitopes and
      given clues to enhancing peptide immunogenicity. Consistent with these
      observations; peptides can be synthesised with defined chemical modifications to
      mimic natural epitopes and/or deliberately introduce protease resistant peptide
      bonds to regulate their processing independent of tissue specific proteolysis and
      to stabilize these compounds in vivo. We discuss the potential of peptide-based
      vaccines for the treatment of chronic viral diseases and cancer and review recent
      developments in the field of epitope discovery and peptide-based vaccines.

PMID- 20687874
TI  - Gene targeting and expression modulation by peptide nucleic acids (PNA).
AB  - Peptide nucleic acids (PNA) are artificial structural mimics of nucleic acids
      capable of sequence specific hybridization to both RNA and DNA. Thus they have
      obvious potential as gene targeting agents for drug discovery approaches. An
      overview with emphasis on recent progress on RNA "interference" (antisense),
      targeting of duplex DNA and gene targeted repair and transcription interference
      using PNA, as well as on PNA delivery and potential PNA anti-infectives is given.

PMID- 20687875
TI  - Synthetic peptides derived from the C-terminal region of Lys49 phospholipase A2
      homologues from viperidae snake venoms: biomimetic activities and potential
      applications.
AB  - Lys49-phospholipase A(2) homologues constitute a large family of toxins present
      in the venoms of viperid snake species, which despite lacking catalytic activity,
      cause significant skeletal muscle necrosis. The main structural determinants of
      this toxic effect have been experimentally mapped to a region near their C
      terminus (115-129), which combines cationic and hydrophobic/aromatic amino acid
      residues. Short (13-mer) synthetic peptides representing this C-terminal region
      can mimick several of the effects of Lys49 PLA(2) homologues. In addition to
      their ability to damage muscle cells, these peptides display antibacterial,
      antiendotoxic, antifungal, antiparasite, and antitumor activities, as well as
      VEGF-receptor 2 (KDR)-binding and heparin-binding properties. Modifications of
      their sequences have shown possibilities to enhance their effects upon
      prokaryotic cells, while decreasing toxicity for eukaryotic cells. This review
      presents an updated summary on the biomimetic actions exerted by such peptides,
      and highlights their potential value as molecular tools or as drug leads in
      diverse biomedical areas.

PMID- 20687876
TI  - Peptides targeting gap junctional structures.
AB  - Cells of multicellular organisms need to communicate and have evolved different
      mechanisms of intercellular communication, the most direct and quickest of which
      is through channels that directly link the cytoplasms of adjacent cells. In
      metazoans, intercellular channels result from the docking of two hemichannels,
      hexameric torus of junctional proteins (connexins being the most known) around an
      aqueous pore. Junctional channels and hemichannels are not passive conduits as
      they had been regarded for a long time but their permeability is finely tuned by
      complex mechanisms that have just begun to be identified, the delay being partly
      due to limited availability of specific pharmacological tools. Peptides have a
      number of advantages over other molecules in terms of specificity and affinity
      for targets. Some of them interact with membrane receptors, activating a
      signaling transduction cascade leading to modifications in the expression of gap
      junctional proteins or the functional state of channels. A second approach is
      based on the use of so-called mimetic peptides (also known as gap peptides) that
      mimic a short sequence of gap junction proteins and have been shown to attenuate
      processes downstream of the putative channel activity. They also represent very
      useful tools to investigate the structure of domains of gap junction proteins.
      This review presents an overview of the literature on peptides targeting gap
      junctional structures.

PMID- 20687877
TI  - HDL apolipoprotein-related peptides in the treatment of atherosclerosis and other
      inflammatory disorders.
AB  - Elevations of HDL levels or modifying the inflammatory properties of HDL are
      being evaluated as possible treatment of atherosclerosis, the underlying
      mechanism responsible for most cardiovascular diseases. A promising approach is
      the use of small HDL apoprotein-related mimetic peptides. A number of peptides
      mimicking the repeating amphipathic alpha-helical structure in apoA-I, the major
      apoprotein in HDL, have been examined in vitro and in animal models. Several
      peptides have been shown to reduce early atherosclerotic lesions, but not more
      mature lesions unless coadministered with statins. These peptides also influence
      the vascular biology of the vessel wall and protect against other acute and
      chronic inflammatory diseases. The biologically active peptides are capable of
      reducing the pro-inflammatory properties of LDL and HDL, likely due to their high
      affinity for oxidized lipids. They are also capable of influencing other
      processes, including ABCA1 mediated activation of JAK-2 in macrophages, which may
      contribute to their anti-atherogenic function. The initial studies involved
      monomeric 18 amino acid peptides, but tandem peptides are being investigated for
      their anti-atherogenic and anti-inflammatory properties as they more closely
      resemble the repeating structure of apoA-I. Peptides based on other HDL
      associated proteins such as apoE, apoJ and SAA have also been studied. Their
      mechanism of action appears to be distinct from the apoA-I based mimetics.

PMID- 20687878
TI  - Chemical modifications designed to improve peptide stability: incorporation of
      non-natural amino acids, pseudo-peptide bonds, and cyclization.
AB  - Functions and properties of native peptides vary from highly specific antibiotics
      or cytotoxic antitumor drugs, to hormones, neurotransmitters, immunomodulators,
      etc. Despite their potential utility as therapeutic agents, there are problems
      connected with the use of natural peptides, due to the low stability against
      proteolysis, resulting in a short duration of in vivo activity, and in a low
      bioavailability. One way to overcome these disadvantages is the use of modified
      peptides, the so called peptidomimetics. Overall, the less peptide character in a
      drug candidate, the more stable it is towards protease cleavage. A huge number of
      non-peptidic scaffolds have been reported in the literature; nevertheless,
      several cases have failed to reproduce the activity of the precursor peptide when
      the scaffold itself contains relevant pharmacophore elements. Therefore, quasi
      peptides still maintain their appeal for applications in medicinal chemistry. For
      the large number of different unnatural amino acids and peptidomimetics, the
      overview cannot be all-inclusive. This review focuses on modified peptides in
      which the peptide character is still preponderant, with particular emphasis on
      the chemical methodologies utilized to introduce the modifications.

PMID- 20687880
TI  - Antimicrobial peptides and peptaibols, substitutes for conventional antibiotics.
AB  - In this review, the antimicrobial properties of a number of peptides are
      described. We first deal with helical linear peptides such as the well-known
      gramicidin, magainins, melittin, and other less well-known or more recently
      discovered peptides. Then, beta-sheet peptides (defensins isolated from insects
      and also from mammalian tissues) and cyclic peptides like amphotericin B are
      described before the properties of peptaibols (containing the non-coded amino
      acid Aib) are discussed. Alamethicin remains the prototype of this class and its
      biophysical properties (mostly focussing on channel- or pore-formation in planar
      lipid bilayers) were and are still intensively studied. On the whole, we show how
      biophysical studies can explain the antimicrobial action of this ever expanding
      family of peptides.

PMID- 20687881
TI  - Neuropeptides as therapeutic approach to autoimmune diseases.
AB  - Because there are no particular molecular signatures of self, autoimmunity is the
      inevitable evolutionary price of being able to make effective responses against a
      wide variety of pathogens by the immune system. Without the various phenomena
      referred to as immune tolerance, the organism would surely self-destruct.
      Considerable evidence suggests that various endogenous neuropeptides play a major
      role in the education of our immune system to be self-tolerant. The fact that
      neuropeptides regulate various layers involved in maintenance of tolerance,
      including regulation of the balance between pro-inflammatory and anti
      inflammatory responses and between self-reactive Th1/Th17 cells and regulatory T
      cells, makes them attractive candidates for the development of new therapies for
      the treatment of autoimmune disorders. Here we use the vasoactive intestinal
      peptide of a prototype of immunomodulatory neuropeptide to review the most
      relevant data found for other neuropeptides with similar characteristics,
      including melanocyte-stimulating hormone, urocortin, adrenomedullin, neuropeptide
      Y, cortistatin and ghrelin. We also evaluate the challenges that must be overcome
      before achieving their clinical application and offer our opinion on how a
      physiologically functional neuropeptide system contributes to general health.

PMID- 20687879
TI  - Ligand-based peptide design and combinatorial peptide libraries to target G
      protein-coupled receptors.
AB  - G protein-coupled receptors (GPCRs) are considered to represent the most
      promising drug targets; it has been repeatedly said that a large fraction of the
      currently marketed drugs elicit their actions by binding to GPCRs (with cited
      numbers varying from 30-50%). Closer scrutiny, however, shows that only a modest
      fraction of (~60) GPCRs are, in fact, exploited as drug targets, only ~20 of
      which are peptide-binding receptors. The vast majority of receptors in the humane
      genome have not yet been explored as sites of action for drugs. Given the
      drugability of this receptor class, it appears that opportunities for drug
      discovery abound. In addition, GPCRs provide for binding sites other than the
      ligand binding sites (referred to as the "orthosteric site"). These additional
      sites include (i) binding sites for ligands (referred to as "allosteric ligands")
      that modulate the affinity and efficacy of orthosteric ligands, (ii) the
      interaction surface that recruits G proteins and arrestins, (iii) the interaction
      sites of additional proteins (GIPs, GPCR interacting proteins that regulate G
      protein signaling or give rise to G protein-independent signals). These sites can
      also be targeted by peptides. Combinatorial and natural peptide libraries are
      therefore likely to play a major role in identifying new GPCR ligands at each of
      these sites. In particular the diverse natural peptide libraries such as the
      venom peptides from marine cone-snails and plant cyclotides have been established
      as a rich source of drug leads. High-throughput screening and combinatorial
      chemistry approaches allow for progressing from these starting points to
      potential drug candidates. This will be illustrated by focusing on the ligand
      based drug design of oxytocin (OT) and vasopressin (AVP) receptor ligands using
      natural peptide leads as starting points.

PMID- 20687882
TI  - Bcl-2 family proteins as therapeutic targets.
AB  - The mitochondrion provides the stage for the interplay of molecular interactions
      that regulate apoptosis via the intrinsic pathway. The release of apoptogenic
      factors from this compartment constitutes a critical juncture in this apoptotic
      pathway. Regulation of the integrity of the outer mitochondrial membrane (OMM) is
      the task of the Bcl-2 family of proteins. A network of interactions between the
      various subgroups of the family decides the apoptotic fate of a cell and, as
      such, an imbalance within this network can lead to a variety of disease states.
      In particular, over-expression of pro-survival Bcl-2 family proteins is a
      hallmark of many cancers. Here we discuss recent advances in targeting the Bcl-2
      family with both peptides and small molecules.

PMID- 20687883
TI  - Orexins/hypocretins: pain regulation and cellular actions.
AB  - Orexin A and B (also named hypocretin 1 and 2) are 33 and 28 amino acid
      containing neuropeptides, respectively, derived from prepro-orexin (prepro
      hypocretin) which is localized in the the lateral and perifonical areas of the
      hypothalamus. Two G-protein coupled receptor subtypes, OX1 and OX2, were
      identified. Orexin-containing fibers and OX receptors are widely distributed in
      the central nervous system. Orexins have been implicated in the arousal,
      rewarding, energy homeostasis, autonomic central control and antinociceptive
      systems. Subtype-selective peptide agonists and antagonists and non-peptide
      antagonists, but not non-peptide agonists, have been developed. This review
      summarizes the studies investigating the antinociceptive effects of orexins in
      various animal models of pain, including trigeminovascular pain, and their
      cellular mechanisms. Orexins are antinociceptive at both spinal and supraspinal
      levels. The antinociceptive effect of orexin A is comparable to opioids but
      orexin B is less or not effective. This effect is opioid-independent and mainly
      mediated through OX1 receptors. Some animal studies suggest that endogenous
      orexins may be released during postoperative and inflammatory, but not acute,
      pain states, or during some stress conditions, which may contribute to stress
      induced analgesia. Purinergic P(2X) and glycine receptors are proposed to be
      involved in orexin-induced spinal antinociception. The supraspinal sites of
      actions might involve the posterior hypothalamus, which contributes to the
      trigeminovascular nociception, and the ventrolateral periaqueductal gray, which
      mediates descending pain inhibition. Endocannobinoids and nociceptin/orphanin FQ
      were found to interplay with orexins in nocicpetive processing. Further studies
      are required to elucidate the receptor subtype-specific mechanism(s) and clinical
      implications of orexin-induced antinociception.

PMID- 20687884
TI  - Optimization and high-throughput screening of antimicrobial peptides.
AB  - While a well-established process for lead compound discovery in for-profit
      companies, high-throughput screening is becoming more popular in basic and
      applied research settings in academia. The development of combinatorial libraries
      combined with easy and less expensive access to new technologies have greatly
      contributed to the implementation of high-throughput screening in academic
      laboratories. While such techniques were earlier applied to simple assays
      involving single targets or based on binding affinity, they have now been
      extended to more complex systems such as whole cell-based assays. In particular,
      the urgent need for new antimicrobial compounds that would overcome the rapid
      rise of drug-resistant microorganisms, where multiple target assays or cell-based
      assays are often required, has forced scientists to focus onto high-throughput
      technologies. Based on their existence in natural host defense systems and their
      different mode of action relative to commercial antibiotics, antimicrobial
      peptides represent a new hope in discovering novel antibiotics against multi
      resistant bacteria. The ease of generating peptide libraries in different formats
      has allowed a rapid adaptation of high-throughput assays to the search for novel
      antimicrobial peptides. Similarly, the availability nowadays of high-quantity and
      high-quality antimicrobial peptide data has permitted the development of
      predictive algorithms to facilitate the optimization process. This review
      summarizes the various library formats that lead to de novo antimicrobial peptide
      sequences as well as the latest structural knowledge and optimization processes
      aimed at improving the peptides selectivity.

PMID- 20687885
TI  - Targets of metabolic toxicity of HIV antiretroviral drugs: the multiple roads to
      lipodystrophy and metabolic syndrome.

PMID- 20687886
TI  - Adipose tissue as a target of HIV-1 antiretroviral drugs. Potential consequences
      on metabolic regulations.
AB  - Adipose tissue redistribution occurred at first in HIV-infected patients about 15
      years ago after initiation of combination antiretroviral treatment (ART) and the
      responsibility of drugs was rapidly considered. This lipodystrophic syndrome can
      associate lipoatrophy, affecting subcutaneous adipose tissue in priority with fat
      hypertrophy, in particular in the upper part of the body, and metabolic
      alterations, dyslipidemia and altered glucose tolerance with insulin resistance.
      The primary role of thymidine analogue reverse transcriptase inhibitors (tNRTI)
      in peripheral lipoatrophy has been clearly shown in vitro and in vivo, these
      drugs inducing a severe mitochondrial dysfunction and an increased oxidative
      stress together with fat inflammation leading to fat loss. In vitro and in vivo
      studies suggest that some protease inhibitors (PI) or non-NRTIs also exert
      adverse effects on adipocytes and could act in synergy to amplify the effect of
      tNRTI. While severe lipoatrophy is now less prevalent in HIV-infected patients,
      fat hypertrophy is frequently observed: a role for drugs from the different
      classes acting in synergy to induce fat hyperplasia and hypertrophy is suggested,
      with milder mitochondrial dysfunction but increased inflammation and activation
      of the cortisol system. In addition, it is now considered that long-term viral
      infection, even if controlled, could induce low-grade inflammation and prepare
      fat to the deleterious effect of ART. Both lipoatrophy and lipohypertrophy are
      involved in metabolic disorders and increased cardio-metabolic risk that likely
      participate to early aging reported in these patients. ART can also be directly
      responsible for metabolic alterations. Strategies to revert or reduce
      lipodystrophy are important to consider in these patients in addition to the
      required control of the metabolic disorders.

PMID- 20687887
TI  - Pharmacogenetics of the metabolic disturbances and atherosclerosis associated
      with antiretroviral therapy in HIV-infected patients.
AB  - The availability of highly active antiretroviral therapy has markedly improved
      the survival rate and quality of life in patients infected with HIV. At present,
      however, there is still no cure for HIV and those undergoing treatment have to do
      so for life. The use of antiretroviral drugs has been associated with several
      toxicities that limit their success. Some acute and chronic toxicities associated
      with these drugs include hypersensitivity reactions, neurotoxicity, nephropathy,
      liver damage, the appearance of body fat redistribution syndrome and the
      different metabolic alterations that accompany it. Some of these toxicities are
      family- or even drug-specific. Since not all patients that take a particular
      antiretroviral medication develop the adverse effect that has been attributed to
      that drug, it has therefore been postulated that there must be a genetically
      conditioned individual predisposition to developing the adverse effect.
      Pharmacogenetics is the science that studies interindividual variations in the
      response to and toxicity of drugs due to variations in the genetic composition of
      individuals. Sufficient advances have been made in this discipline to allow this
      fertile field of research to move out of the basic science laboratory and into
      clinical applications. The present article reviews the investigations that have
      been published regarding the association between the genetic determinants of
      persons infected with HIV and the metabolic toxicity and chronic vascular
      consequences resulting from antiretroviral drugs. The influence of host genetic
      variants on dyslipidemia, hyperglycemia and insulin resistance, lipodystrophy and
      atherosclerosis are presented and discussed.

PMID- 20687888
TI  - Lipotoxicity on the basis of metabolic syndrome and lipodystrophy in HIV-1
      infected patients under antiretroviral treatment.
AB  - The development of efficacious antiretroviral drugs that minimize adverse effects
      is a current challenge in HIV-1 therapy. Metabolic alterations reminiscent of the
      metabolic syndrome and overt lipodystrophy appear often in HIV-1-infected
      patients undergoing antiretroviral treatment. The etiopathogenesis of these
      alterations is complex, but lipotoxicity has recently emerged as a key concept
      for explaining the metabolic syndrome in HIV-1-infected patients, similarly to
      what has been observed in diseases such as obesity and genetic lipodystrophies.
      Antiretroviral drugs from distinct drug families may directly elicit such
      lipotoxic phenomena, via increased lipolysis, enhanced adipocyte apoptosis and
      impaired adipogenesis, which collectively lead to a reduced capacity of
      subcutaneous adipose tissue to enlarge to meet fat storage requirements. Thus,
      fatty acids that cannot be properly stored as triglycerides in subcutaneous
      adipose tissue are expected to accumulate in visceral fat as well as in organs
      and tissues, such as the pancreas, muscle and liver, leading to the pattern of
      metabolic alterations associated with abnormal ectopic fat accumulation, mainly
      insulin resistance. Inflammatory responses, evoked by the combined effects of
      antiretroviral drugs and the underlying HIV-1 infection, also contribute to
      lipotoxicity, reflecting the action of pro-inflammatory cytokines that enhance
      lipolytic activity in adipose tissue and impair adipogenesis. Minimizing the
      lipotoxic action of antiretroviral drugs is ultimately essential in reducing
      metabolic alterations in treated patients. Moreover, pharmacological strategies
      that reduce lipotoxicity and promote adipose tissue expandability can be expected
      to ameliorate the overall metabolic abnormalities in HIV-1-infected,
      antiretroviral-treated patients.

PMID- 20687889
TI  - Contribution of inflammation to fat redistribution and metabolic disturbances in
      HIV-1 infected patients.
AB  - Antiretroviral therapy (ART) has significantly reduced the morbidity and
      mortality of patients infected with the human immunodeficiency virus 1 (HIV-1).
      In a significant number of patients, ART is associated with fat redistribution
      and metabolic alterations such as dyslipidemia, insulin resistance (IR) and type
      2 diabetes, summarized under the term HIV-associated lipodystrophy syndrome (HIV
      LS). The pathogenesis of HIV-LS is complex and involves a number of factors
      including ART, HIV-1, abnormal fat redistribution, metabolic abnormalities and
      chronic inflammation. In view of a novel understanding on how chronic
      inflammation contributes to the pathogenesis of HIV-1 infection, this review
      focuses on the interaction of the immune system and metabolic pathways and the
      potential consequences for the HIV-LS. Based on the current literature, we
      suggest a central role of systemic inflammation in triggering and deteriorating
      various components of the HIV-LS.

PMID- 20687890
TI  - Impact of mitochondrial toxicity of HIV-1 antiretroviral drugs on lipodystrophy
      and metabolic dysregulation.
AB  - Nucleoside reverse transcriptase inhibitors (NRTIs) are components of most
      current antiretroviral (ARV) regimens. Side effects arising from mitochondrial
      toxicity (MtT) induced by these drugs is a common reason why patients treated
      with NRTI change or discontinue therapy. These toxicities can be difficult to
      reverse, and on occasion can be life-threatening. The exact pathogenesis
      underlying NRTI-induced mitochondrial toxicity remains unclear, and likely
      differs for specific NRTI drugs. We review mitochondrial physiology, what is
      known about how NRTI cause MtT, and what areas of pathophysiology remain unclear.
      Using the example of HIV-associated lipodystrophy (HIVLD) as a model of clinical
      MtT we discuss management strategies and the potential for these toxicities to
      impact on future ARV development.

PMID- 20687891
TI  - Lactobacillus rhamnosus cell lysate in the management of resistant childhood
      atopic eczema.
AB  - The number of children suffering from atopic eczema has increased over the past
      30 years especially in children between the ages of 2 and 5 years. These is a
      significant group of eczematous children that are resistant to standard therapy.
      Babies and children with eczema suffer pain, irritation and disfigurement from
      the dermatitis. In this study, we have followed 14 cases of pediatric patients
      (ages of 8 months to 64 months) with a history of resistant eczema for a period
      of at least six months. All of these children received 300 mg to 500 mg
      standardized Lactobacillus rhamnosus cell lysate daily as an immunobiotic
      supplement. The results of this open label non-randomized clinical observation
      showed a substantial improvement in quality of life, skin symptoms and day- and
      nighttime irritation scores in children with the supplementation of Lactobacillus
      rhamnosus lysate. There were no intolerance or adverse reactions observed in
      these children. Lactobacillus rhamnosus cell lysate may thus be used as a safe
      and effective immunobiotic for the treatment and prevention of childhood eczema
      and possible other types of atopy (allergic diseases).

PMID- 20687892
TI  - The role of nuclear factor-kappaB in inflammatory lung disease.
AB  - Nuclear factor-kappaB (NF-kappaB) is one of the most important transcription
      factors; it has a key role in inflammatory and immune responses, cell adhesion,
      developmental signals, and anti-apoptosis process. Inflammatory lung diseases
      such as asthma and chronic obstructive pulmonary disease (COPD) are major causes
      of morbidity and mortality worldwide. In this review, we highlight the role of NF
      kappaB in inflammatory lung disease, the strategies which block the activation of
      NF-kappaB, and the therapeutic approaches to treating inflammatory lung disease.

PMID- 20687893
TI  - Seeing is believing: molecular imaging in living subjects.

PMID- 20687894
TI  - Comparative analysis of stage specific gene regulation of apicomplexan parasites:
      Plasmodium falciparum and Toxoplasma gondii.

PMID- 20687895
TI  - Bivalirudin in patients with coronary artery disease.
AB  - Bivalirudin, a DTI, has evolved from relative obscurity as an anticoagulation
      option in patients resistant to or allergic to either LMWH or UFH to a commonly
      used, safe alternative. Most of the early studies comparing bivalirudin to UFH
      with or without a GP IIb/IIIa agent had composite endpoints (death, MI, bleeding)
      whose statistical significance were driven exclusively by a significant reduction
      in bleeding. Newer studies now demonstrate reductions in mortality, which has led
      to a paradigm shift in anticoagulant choice both in elective and emergent
      coronary procedures. We present the major studies that have brought bivalirudin
      to the forefront of coronary artery disease, specifically coronary interventional
      procedures.

PMID- 20687896
TI  - Amoxicillin-bearing microparticles: potential in the treatment of Listeria
      monocytogenes infection in Swiss albino mice.
AB  - The present study was aimed at evaluating the effectiveness of amoxicillin
      bearing HSA (human serum albumin) and PLGA [poly(lactic-co-glycolic acid)]
      microparticles in combating Listeria monocytogenes infection in Swiss albino
      mice. Amoxicillin-bearing HSA microspheres were prepared by chemical cross
      linking of a drug/albumin mixture with glutaraldehyde, and PLGA microspheres were
      prepared by the W/O/W (water-in-oil-in-water) emulsion technique. The
      microspheres were characterized for their size, zeta potential and entrapment
      efficiency using SEM (scanning electron microscopy) and a Zetasizer. Release
      kinetics was performed in a phosphate buffer (pH 7.4) at 37 degrees C simulating
      physiological conditions. Bacterial burden in various vital organs and survival
      data established enhanced efficacy of PLGA and HSA microspheres as compared with
      free drug. Among the two delivery systems, PLGA microspheres, when compared with
      HSA microspheres, imparted better efficacy in terms of reduction in bacterial
      load as well as increase in survival. The results of the present study clearly
      demonstrate that microparticles successfully target the infected macrophages and
      the approach could be well exploited for targeting the intracellular pathogens as
      well.

PMID- 20687897
TI  - Human INO80 chromatin-remodelling complex contributes to DNA double-strand break
      repair via the expression of Rad54B and XRCC3 genes.
AB  - Recent studies have shown that the SWI/SNF family of ATP-dependent chromatin
      remodelling complexes play important roles in DNA repair as well as in
      transcription. The INO80 complex, the most recently described member of this
      family, has been shown in yeast to play direct role in DNA DSB (double-strand
      break) repair without affecting the expression of the genes involved in this
      process. However, whether this function of the INO80 complex is conserved in
      higher eukaryotes has not been investigated. In the present study, we found that
      knockdown of hINO80 (human INO80) confers DNA-damage hypersensitivity and
      inefficient DSB repair. Microarray analysis and other experiments have identified
      the Rad54B and XRCC3 (X-ray repair complementing defective repair in Chinese
      hamster cells 3) genes, implicated in DSB repair, to be repressed by hINO80
      deficiency. Chromatin immunoprecipitation studies have shown that hINO80 binds to
      the promoters of the Rad54B and XRCC3 genes. Re-expression of the Rad54B and
      XRCC3 genes rescues the DSB repair defect in hINO80-deficient cells. These
      results suggest that hINO80 assists DSB repair by positively regulating the
      expression of the Rad54B and XRCC3 genes. Therefore, unlike yeast INO80, hINO80
      can contribute to DSB repair indirectly via gene expression, suggesting that the
      mechanistic role of this chromatin remodeller in DSB repair is evolutionarily
      diversified.

PMID- 20687898
TI  - Heart 6-phosphofructo-2-kinase activation by insulin requires PKB (protein kinase
      B), but not SGK3 (serum- and glucocorticoid-induced protein kinase 3).
AB  - On the basis of transfection experiments using a dominant-negative approach, our
      previous studies suggested that PKB (protein kinase B) was not involved in heart
      PFK-2 (6-phosphofructo2-kinase) activation by insulin. Therefore we first tested
      whether SGK3 (serum- and glucocorticoid-induced protein kinase 3) might be
      involved in this effect. Treatment of recombinant heart PFK-2 with [gamma-32P]ATP
      and SGK3 in vitro led to PFK-2 activation and phosphorylation at Ser466 and
      Ser483. However, in HEK-293T cells [HEK (human embryonic kidney)-293 cells
      expressing the large T-antigen of SV40 (simian virus 40)] co-transfected with
      SGK3 siRNA (small interfering RNA) and heart PFK-2, insulin-induced heart PFK-2
      activation was unaffected. The involvement of PKB in heart PFK-2 activation by
      insulin was re-evaluated using different models: (i) hearts from transgenic mice
      with a muscle/heart-specific mutation in the PDK1 (phosphoinositide-dependent
      protein kinase 1)-substrate-docking site injected with insulin; (ii) hearts from
      PKBbeta-deficient mice injected with insulin; (iii) freshly isolated rat
      cardiomyocytes and perfused hearts treated with the selective Akti-1/2 PKB
      inhibitor prior to insulin treatment; and (iv) HEK-293T cells co-transfected with
      heart PFK-2, and PKBalpha/beta siRNA or PKBalpha siRNA, incubated with insulin.
      Together, the results indicated that SGK3 is not required for insulin-induced PFK
      2 activation and that this effect is likely mediated by PKBalpha.

PMID- 20687899
TI  - Exercise-induced changes in interleukin-10 in patients with knee osteoarthritis:
      new perspectives?
AB  - Osteoarthritis (OA) of the knee is a common chronic disease leading to increased
      morbidity and reduced quality of life. Although exercise therapy has been shown
      to be beneficial for both pain and physical functioning, its underlying mechanism
      is not fully understood. However, a recent study found an exercise-induced
      increase in interleukin-10 levels, to which anti-inflammatory and
      chondroprotective properties are ascribed, in the (peri-)synovial fluid of
      patients with knee OA. These interesting results provide more insight into the
      effects of exercise in OA and need to be validated and confirmed. Hopefully, the
      study offers a promising basis for further research.

PMID- 20687900
TI  - Prenatal diagnosis of fetal aneuploidies: post-genomic developments.
AB  - Prenatal diagnosis of fetal aneuploidies and chromosomal anomalies is likely to
      undergo a profound change in the near future. On the one hand this is mediated by
      new technical developments, such as chromosomal microarrays, which allow a much
      more precise delineation of minute sub-microscopic chromosomal aberrancies than
      the classical G-band karyotype. This will be of particular interest when
      investigating pregnancies at risk of unexplained development delay, intellectual
      disability or certain forms of autism. On the other hand, great strides have been
      made in the non-invasive determination of fetal genetic traits, largely through
      the analysis of cell-free fetal nucleic acids. It is hoped that, with the
      assistance of cutting-edge tools such as digital PCR or next generation
      sequencing, the long elusive goal of non-invasive prenatal diagnosis for fetal
      aneuploidies can finally be attained.

PMID- 20687901
TI  - Bcl-xL affects the development of functional CD4 Tregs.

PMID- 20687902
TI  - Quality of life in patients aged 80 or over after intensive care unit discharge.

PMID- 20687903
TI  - Is routine autopsy in the intensive care unit viable? Authors' response.

PMID- 20687904
TI  - Osseous metaplasia of the endometrium associated with infertility: a case report
      and review of the literature.
AB  - INTRODUCTION: Endometrial ossification is an uncommon disease related to
      secondary infertility and its etiology and pathogenesis are controversial. More
      than 80% of reported cases occur after pregnancy. CASE PRESENTATION: A 33-year
      old Caucasian woman was admitted with a history of secondary infertility and with
      a regular menstrual cycle. She reported a miscarriage at 12 weeks of gestation 7
      years previously and subsequent dilatation and curettage in another medical
      facility. Vaginal ultrasound was performed and showed an intrauterine structure
      described as a hyperechogenic image suggesting calcification related to chronic
      endometritis. Office hysteroscopy revealed a wide endometrial cavity and
      proliferative endometrium, with a coral-like white plaque 1.5 cm in length on the
      right horn and posterior wall of the uterus. The lesion was treated by
      hysteroscopy without complications. Microscopic examination showed endometrial
      tissue with osseous metaplasia in the stroma. Nine months after the procedure,
      the patient became pregnant spontaneously. CONCLUSION: In our patient,
      hysteroscopy was effective in the diagnosis and treatment of osseous metaplasia
      of the endometrium associated with infertility.

PMID- 20687905
TI  - A little bit is better than nothing: the incomplete parthenogenesis of
      salamanders, frogs and fish.
AB  - A re-examination of the mitochondrial genomes of unisexual salamander lineages,
      published in BMC Evolutionary Biology, shows them to be the oldest unisexual
      vertebrates known, having been around for 5 million years. This presents a
      challenge to the prediction that lack of genetic recombination is a fast track to
      extinction. See research article http://www.biomedcentral.com/1471-2148/10/238.

PMID- 20687906
TI  - Losing the desire: selection can promote obligate asexuality.
AB  - Whilst parthenogenesis has evolved multiple times from sexual invertebrate and
      vertebrate lineages, the drivers and consequences of the sex-asex transition
      remain mostly uncertain. A model by Stouthamer et al. recently published in BMC
      Evolutionary Biology shows a pathway by which obligate asexuality could be
      selected for following endosymbiont infection. See research article
      http://www.biomedcentral.com/1471-2148/10/229.

PMID- 20687907
TI  - Vertebrate Hedgehog signaling: cilia rule.
AB  - The Hedgehog (Hh) signaling pathway differentially utilizes the primary cilium in
      mammals and fruit flies. Recent work, including a study in BMC Biology,
      demonstrates that Hh signals through the cilium in zebrafish, clarifying the
      evolution of Hh signal transduction. See research article:
      http://www.biomedcentral.com/1741-7007/8/65.

PMID- 20687908
TI  - Insulators and imprinting from flies to mammals.
AB  - The nuclear factor CTCF has been shown to be necessary for the maintenance of
      genetic imprinting at the mammalian H19/Igf2 locus. MacDonald and colleagues now
      report in BMC Biology that the mechanisms responsible for maintaining the
      imprinted state in Drosophila may be evolutionarily conserved and that CTCF may
      also play a critical role in this process. See research article
      http://www.biomedcentral.com/1741-7007/8/105.

PMID- 20687909
TI  - The impact of attrition on the representativeness of cohort studies of older
      people.
AB  - BACKGROUND: There are well-established risk factors, such as lower education, for
      attrition of study participants. Consequently, the representativeness of the
      cohort in a longitudinal study may deteriorate over time. Death is a common form
      of attrition in cohort studies of older people. The aim of this paper is to
      examine the effects of death and other forms of attrition on risk factor
      prevalence in the study cohort and the target population over time. METHODS:
      Differential associations between a risk factor and death and non-death attrition
      are considered under various hypothetical conditions. Empirical data from the
      Australian Longitudinal Study on Women's Health (ALSWH) for participants born in
      1921-26 are used to identify associations which occur in practice, and national
      cross-sectional data from Australian Censuses and National Health Surveys are
      used to illustrate the evolution of bias over approximately ten years. RESULTS:
      The hypothetical situations illustrate how death and other attrition can
      theoretically affect changes in bias over time. Between 1996 and 2008, 28.4% of
      ALSWH participants died, 16.5% withdrew and 10.4% were lost to follow up. There
      were differential associations with various risk factors, for example, non
      English speaking country of birth was associated with non-death attrition but not
      death whereas being underweight (body mass index < 18.5) was associated with
      death but not other forms of attrition. Compared to national data,
      underrepresentation of women with non-English speaking country of birth increased
      from 3.9% to 7.2% and over-representation of current and ex-smoking increased
      from 2.6% to 5.8%. CONCLUSIONS: Deaths occur in both the target population and
      study cohort, while other forms of attrition occur only in the study cohort.
      Therefore non-death attrition may cause greater bias than death in longitudinal
      studies. However although more than a quarter of the oldest participants in the
      ALSWH died in the 12 years following recruitment, differences from the national
      population changed only slightly.

PMID- 20687910
TI  - Tumor cell-derived PDGF-B potentiates mouse mesenchymal stem cells-pericytes
      transition and recruitment through an interaction with NRP-1.
AB  - BACKGROUND: New blood vessel formation, or angiogenic switch, is an essential
      event in the development of solid tumors and their metastatic growth. Tumor blood
      vessel formation and remodeling is a complex and multi-step processes. The
      differentiation and recruitment of mural cells including vascular smooth muscle
      cells and pericytes are essential steps in tumor angiogenesis. However, the role
      of tumor cells in differentiation and recruitment of mural cells has not yet been
      fully elucidated. This study focuses on the role of human tumor cells in
      governing the differentiation of mouse mesenchymal stem cells (MSCs) to pericytes
      and their recruitment in the tumor angiogenesis process. RESULTS: We show that
      C3H/10T1/2 mouse embryonic mesenchymal stem cells, under the influence of
      different tumor cell-derived conditioned media, differentiate into mature
      pericytes. These differentiated pericytes, in turn, are recruited to bind with
      capillary-like networks formed by endothelial cells on the matrigel under in
      vitro conditions and recruited to bind with blood vessels on gel-foam under in
      vivo conditions. The degree of recruitment of pericytes into in vitro neo
      angiogenesis is tumor cell phenotype specific. Interestingly, invasive cells
      recruit less pericytes as compared to non-invasive cells. We identified tumor
      cell-secreted platelet-derived growth factor-B (PDGF-B) as a crucial factor
      controlling the differentiation and recruitment processes through an interaction
      with neuropilin-1 (NRP-1) in mesenchymal stem cells. CONCLUSION: These new
      insights into the roles of tumor cell-secreted PDGF-B-NRP-1 signaling in MSCs
      fate determination may help to develop new antiangiogenic strategies to prevent
      the tumor growth and metastasis and result in more effective cancer therapies.

PMID- 20687911
TI  - Spread of a highly mucoid Streptococcus pyogenes emm3/ST15 clone.
AB  - BACKGROUND: Hyaluronic acid capsule plays a key role in Streptococcus pyogenes
      virulence. Circulation of mucoid or highly encapsulated strains has been related
      to rheumatic fever epidemics and invasive disease in several countries. In 2009,
      an outbreak of mucoid S. pyogenes isolates was detected in northern Spain. The
      aim of the study was to describe clinical and molecular characteristics of mucoid
      strains causing this outbreak and to compare them with a sample of non-mucoid S.
      pyogenes isolates obtained during the same period of time. METHODS: All S.
      pyogenes isolates with a mucoid colony morphology (n = 132), 10% of non-mucoid (n
      = 144) and all invasive S. pyogenes isolates (n = 7) obtained in 2009 were
      included. Characterization was performed by T-agglutination, emm typing, pulsed
      field gel electrophoresis and multilocus sequence typing. RESULTS: One clone
      characterized as emm3.1/ST15 comprised 98.5% (n = 130) of all mucoid isolates.
      Subjects of all ages were affected. Main clinical manifestations were pharyngitis
      and scarlet fever, but this clone also caused invasive disease: two cases of
      streptococcal toxic shock syndrome, one arthritis, and one celullitis with a
      fatal outcome. Mucoid isolates were more prone to cause invasive disease than non
      mucoid isolates (p = 0.001). CONCLUSIONS: Although no acute rheumatic fever cases
      were detected, the most worrisome characteristics of this clone were the success
      for causing invasive disease and the merge of two virulent features: the
      serotype, emm3, and capsule hyper-production, expressed as a mucoid morphology.

PMID- 20687912
TI  - Resource utilization and outcomes of intoxicated drivers.
AB  - BACKGROUND: The high risk behavior of intoxicated drivers, impaired reaction
      time, lack of seat belt use, and increased incidence of head injury raises
      questions of whether pre-hospital use of alcohol leads to a higher injury
      severity score and worse clinical outcomes. We therefore compared intoxicated and
      non-intoxicated drivers of motor vehicle crashes with respect to outcome
      measurements and also describe the resources utilized to achieve those outcomes
      at our Level 1 trauma center. METHODS: Retrospective descriptive study (Jan 2002
      June 2007) of our trauma registry and financial database comparing intoxicated
      drivers with blood alcohol levels (BAC) > 80 mg/dl (ETOH > 80) with drivers who
      had a BAC of 0 mg/dl (ETOH = 0). Drivers without a BAC drawn or who had levels
      ranging from 1 mg/dL to 80 mg/dL were excluded. Data was collected on demographic
      information (age, gender, injury severity score or ISS), outcome variables
      (mortality, complications, ICU and hospital LOS, ventilator days) and resource
      utilization (ED LOS, insurance, charges, costs, payments). STATISTICAL ANALYSIS:
      p < 0.05 vs. ETOH > 80; stratified chi square. RESULTS: Out of 1732 drivers, the
      combined study group (n = 987) of 623 ETOH = 0 and 364 ETOH > 80 had a mean age
      of 38.8 +/- 17.9, ISS of 18.0 +/- 12.1, and 69.8%% male. There was no difference
      in ISS (p = 0.67) or complications (p = 0.38). There was a trend towards
      decreased mortality (p = 0.06). The ETOH = 0 group had more patients with a
      prolonged ICU LOS (>/= 5 days), ventilator days (>/= 8 days), and hospital LOS (>
      14 days) when compared to the ETOH > 80 group (p < 0.05). The ETOH > 80 group
      tended to be self pay (4.9% vs. 0.7%, p < 0.5) and less likely to generate
      payment for hospital charges (p < 0.5). Hospital charges and costs were higher in
      the ETOH = 0 group (p < 0.5). CONCLUSIONS: The data suggests that intoxicated
      drivers may have better outcomes and a trend towards reduced mortality. They
      appeared to be less likely to have prolonged hospital LOS, ICU LOS, and
      ventilator days. We also observed that intoxicated drivers were more likely to be
      self-pay, less likely to have charges > $50K, and less likely to pay >/= 90% of
      the charges. Further research using multivariable analysis is needed to determine
      if these apparent outcomes differences are driven by acute intoxication, and the
      tendency for endotracheal intubation and ICU admission, rather than injury
      severity.

PMID- 20687913
TI  - Editorial Commentary: Resource utilization and outcomes of intoxicated drivers:
      does evidence of alcohol-impaired driving affect road traffic crash injury
      outcomes?

PMID- 20687914
TI  - A kinetic model of TBP auto-regulation exhibits bistability.
AB  - BACKGROUND: TATA Binding Protein (TBP) is required for transcription initiation
      by all three eukaryotic RNA polymerases. It participates in transcriptional
      initiation at the majority of eukaryotic gene promoters, either by direct
      association to the TATA box upstream of the transcription start site or by
      indirectly localizing to the promoter through other proteins. TBP exists in
      solution in a dimeric form but binds to DNA as a monomer. Here, we present the
      first mathematical model for auto-catalytic TBP expression and use it to study
      the role of dimerization in maintaining the steady state TBP level. RESULTS: We
      show that the autogenous regulation of TBP results in a system that is capable of
      exhibiting three steady states: an unstable low TBP state, one stable state
      corresponding to a physiological TBP concentration, and another stable steady
      state corresponding to unviable cells where no TBP is expressed. Our model
      predicts that a basal level of TBP is required to establish the transcription of
      the TBP gene, and hence for cell viability. It also predicts that, for the
      condition corresponding to a typical mammalian cell, the high-TBP state and cell
      viability is sensitive to variation in DNA binding strength. We use the model to
      explore the effect of the dimer in buffering the response to changes in TBP
      levels, and show that for some physiological conditions the dimer is not
      important in buffering against perturbations. CONCLUSIONS: Results on the
      necessity of a minimum basal TBP level support the in vivo observations that TBP
      is maternally inherited, providing the small amount of TBP required to establish
      its ubiquitous expression. The model shows that the system is sensitive to
      variations in parameters indicating that it is vulnerable to mutations in TBP. A
      reduction in TBP-DNA binding constant can lead the system to a regime where the
      unviable state is the only steady state. Contrary to the current hypotheses, we
      show that under some physiological conditions the dimer is not very important in
      restoring the system to steady state. This model demonstrates the use of
      mathematical modelling to investigate system behaviour and generate hypotheses
      governing the dynamics of such nonlinear biological systems.

PMID- 20687915
TI  - An economic appraisal of the Australian Medical Sheepskin for the prevention of
      sacral pressure ulcers from a nursing home perspective.
AB  - BACKGROUND: Many devices are in use to prevent pressure ulcers, but from most
      little is known about their effects and costs. One such preventive device is the
      Australian Medical Sheepskin that has been proven effective in three randomized
      trials. In this study the costs and savings from the use of the Australian
      Medical Sheepskin were investigated from the perspective of a nursing home.
      METHODS: An economic model was developed in which monetary costs and monetary
      savings in respect of the sheepskin were balanced against each other. The model
      was applied to a fictional (Dutch) nursing home with 100 beds for rehabilitation
      patients and a time horizon of one year. Input variables for the model consisted
      of investment costs for using the sheepskin (purchase and laundry), and savings
      through the prevented cases of pressure ulcers. The input values for the
      investment costs and for the effectiveness were empirically based on a trial with
      newly admitted rehabilitation patients from eight nursing homes. The input values
      for the costs of pressure ulcer treatment were estimated by means of four
      different approaches. RESULTS: Investment costs for using the Australian Medical
      Sheepskin were larger than the monetary savings obtained by preventing pressure
      ulcers. Use of the Australian Medical Sheepskin involves an additional cost of
      approximately 2 euro per patient per day. Preventing one case of a sacral
      pressure ulcer by means of the Australian Medical Sheepskin involves an
      investment of 2,974 euro when the sheepskin is given to all patients. When the
      sheepskin is selectively used for more critical patients only, the investment to
      prevent one case of sacral pressure ulcers decreases to 2,479 euro (pressure
      ulcer risk patients) or 1,847 euro (ADL-severely impaired patients). The factors
      with the strongest influence on the balance are the frequency of changing the
      sheepskin and the costs of washing related to this. The economic model was
      hampered by considerable uncertainty in the estimations of the costs of pressure
      ulcer treatment. CONCLUSIONS: From a nursing home perspective, the investment
      costs for use of the Australian Medical Sheepskin in newly admitted
      rehabilitation patients are larger than the monetary savings obtained by
      preventing pressure ulcers.

PMID- 20687916
TI  - mab-31 and the TGF-beta pathway act in the ray lineage to pattern C. elegans male
      sensory rays.
AB  - BACKGROUND: C. elegans TGF-beta-like Sma/Mab signaling pathway regulates both
      body size and sensory ray patterning. Most of the components in this pathway were
      initially identified by genetic screens based on the small body phenotype, and
      many of these mutants display sensory ray patterning defect. At the cellular
      level, little is known about how and where these components work although ray
      structural cell has been implicated as one of the targets. Based on the specific
      ray patterning abnormality, we aim to identify by RNAi approach additional
      components that function specifically in the ray lineage to elucidate the
      regulatory role of TGF-beta signaling in ray differentiation. RESULT: We report
      here the characterization of a new member of the Sma/Mab pathway, mab-31,
      recovered from a genome-wide RNAi screen. mab-31 mutants showed ray cell cluster
      patterning defect and mis-specification of the ray identity. mab-31 encodes a
      nuclear protein expressed in descendants of ray precursor cells impacting on the
      ray cell's clustering properties, orientation of cell division plane, and fusion
      of structural cells. Genetic experiments also establish its relationship with
      other Sma/Mab pathway components and transcription factors acting upstream and
      downstream of the signaling event. CONCLUSION: mab-31 function is indispensable
      in Sma/Mab signal recipient cells during sensory rays specification. Both mab-31
      and sma-6 are required in ray lineage at the late larval stages. They act
      upstream of C. elegans Pax-6 homolog and repress its function. These findings
      suggested mab-31 is a key factor that can integrate TFG-beta signals in male
      sensory ray lineage to define organ identity.

PMID- 20687917
TI  - Protocol for the adolescent hayfever trial: cluster randomised controlled trial
      of an educational intervention for healthcare professionals for the management of
      school-age children with hayfever.
AB  - BACKGROUND: Seasonal allergic rhinitis (hayfever) is common and can contribute to
      a considerable reduction in the quality of life of adolescents. This study aims
      to examine the effectiveness of standardised allergy training for healthcare
      professionals in improving disease-specific quality of life in adolescents with
      hayfever. METHODS/DESIGN: Adolescents with a history of hayfever registered in
      general practices in Scotland and England were invited to participate in a
      cluster randomised controlled trial. The unit of randomisation is general
      practices.The educational intervention for healthcare professionals consists of a
      short standardised educational course, which focuses on the management of
      allergic rhinitis. Patients in the intervention arm of this cluster randomised
      controlled trial will have a clinic appointment with their healthcare
      professional who has attended the training course. Patients in the control arm
      will have a clinic appointment with their healthcare professional and will
      receive usual care. The primary outcome measure is the change in the
      Rhinoconjunctivitis Quality of Life Questionnaire with Standardised Activities
      (RQLQ(S)) score between baseline and six weeks post-intervention in the patient
      intervention and control groups. Secondary outcome measures relate to healthcare
      professionals' understanding and confidence in managing allergic rhinitis,
      changes in clinical practice, numbers of consultations for hayfever and
      adolescent exam performance.A minimum of 11 practices in each arm of the trial
      (10 patients per cluster) will provide at least 80% power to demonstrate a
      minimal clinically important difference of 0.5 in RQLQ(S) score at a significance
      level of 5% based on an Intraclass Correlation Coefficient (ICC) of 0.02.
      DISCUSSION: At the time of submission, 24 general practices have been recruited
      (12 in each arm of the trial) and the interventions have been delivered. Follow
      up data collection is complete. 230 children consented to take part in the trial;
      however complete primary outcome data are only available for 160. Further
      recruitment of general practices and patients will therefore take place in the
      summer of 2010. TRIAL REGISTRATION: Current Controlled Trials ISRCTN95538067.

PMID- 20687918
TI  - Testing the interaction between analytical modules: an example with Roundup Ready
      soybean line GTS 40-3-2.
AB  - BACKGROUND: The modular approach to analysis of genetically modified organisms
      (GMOs) relies on the independence of the modules combined (i.e. DNA extraction
      and GM quantification). The validity of this assumption has to be proved on the
      basis of specific performance criteria. RESULTS: An experiment was conducted
      using, as a reference, the validated quantitative real-time polymerase chain
      reaction (PCR) module for detection of glyphosate-tolerant Roundup Ready(R) GM
      soybean (RRS). Different DNA extraction modules (CTAB, Wizard and Dellaporta),
      were used to extract DNA from different food/feed matrices (feed, biscuit and
      certified reference material [CRM 1%]) containing the target of the real-time PCR
      module used for validation. Purity and structural integrity (absence of
      inhibition) were used as basic criteria that a DNA extraction module must satisfy
      in order to provide suitable template DNA for quantitative real-time (RT) PCR
      based GMO analysis. When performance criteria were applied (removal of non
      compliant DNA extracts), the independence of GMO quantification from the
      extraction method and matrix was statistically proved, except in the case of
      Wizard applied to biscuit. A fuzzy logic-based procedure also confirmed the
      relatively poor performance of the Wizard/biscuit combination. CONCLUSIONS: For
      RRS, this study recognises that modularity can be generally accepted, with the
      limitation of avoiding combining highly processed material (i.e. biscuit) with a
      magnetic-beads system (i.e. Wizard).

PMID- 20687919
TI  - Parotid fistula secondary to suppurative parotitis in a 13-year-old girl: a case
      report.
AB  - INTRODUCTION: The most common cause of parotid fistula is trauma, followed by
      malignancy, operative complications (parotidectomy or rhytidectomy) and
      infection. Acute suppurative parotitis can rarely produce parotid fistula. There
      are various treatment options available, however it is necessary to standardize
      the treatment according to the duration of history and the patient's general
      condition. CASE REPORT: A 13-year-old Indo-Caucasian girl presented to us with a
      two-year history of clear watery discharge from a wound just above and behind the
      angle of her right jaw. A diagnosis of salivary (parotid) fistula was made based
      on clinical examination and investigations. The parotid fistula was successfully
      managed. CONCLUSION: Parotid fistula secondary to suppurative parotitis is rare
      and difficult to manage successfully. Meticulous dissection, complete excision of
      the fistulous tract with closure of the parotid fascia and layered closure of the
      incision followed by application of a post-operative pressure bandage,
      anticholinergic agents and antibiotics contribute significantly to the successful
      management of this difficult clinical condition.

PMID- 20687920
TI  - A systematic review of randomized controlled trials exploring the effect of
      immunomodulative interventions on infection, organ failure, and mortality in
      trauma patients.
AB  - INTRODUCTION: Following trauma, patients may suffer an overwhelming pro
      inflammatory response and immune paralysis resulting in infection and multiple
      organ failure (MOF). Various potentially immunomodulative interventions have been
      tested. The objective of this study is to systematically review the randomized
      controlled trials (RCTs) that investigate the effect of potentially
      immunomodulative interventions in comparison to a placebo or standard therapy on
      infection, MOF, and mortality in trauma patients. METHODS: A computerized search
      of MEDLINE, the Cochrane CENTRAL Register of Controlled Trials, and EMBASE
      yielded 502 studies, of which 18 unique RCTs were deemed relevant for this study.
      The methodological quality of these RCTs was assessed using a critical appraisal
      checklist for therapy articles from the Centre for Evidence Based Medicine. The
      effects of the test interventions on infection, MOF, and mortality rates and
      inflammatory parameters relative to the controls were recorded. RESULTS: In most
      studies, the inflammatory parameters differed significantly between the test and
      control groups. However, significant changes in infection, MOF, and mortality
      rates were only measured in studies testing immunoglobulin, IFN-gamma, and
      glucan. CONCLUSIONS: Based on level 1b and 2b studies, administration of
      immunoglobulin, IFN-gamma, or glucan have shown the most promising results to
      improve the outcome of trauma patients.

PMID- 20687921
TI  - Extraction of user's navigation commands from upper body force interaction in
      walker assisted gait.
AB  - BACKGROUND: The advances in technology make possible the incorporation of sensors
      and actuators in rollators, building safer robots and extending the use of
      walkers to a more diverse population. This paper presents a new method for the
      extraction of navigation related components from upper-body force interaction
      data in walker assisted gait. A filtering architecture is designed to cancel: (i)
      the high-frequency noise caused by vibrations on the walker's structure due to
      irregularities on the terrain or walker's wheels and (ii) the cadence related
      force components caused by user's trunk oscillations during gait. As a result, a
      third component related to user's navigation commands is distinguished. RESULTS:
      For the cancelation of high-frequency noise, a Benedict-Bordner g-h filter was
      designed presenting very low values for Kinematic Tracking Error ((2.035 +/-
      0.358).10(-2) kgf) and delay ((1.897 +/- 0.3697).10(1)ms). A Fourier Linear
      Combiner filtering architecture was implemented for the adaptive attenuation of
      about 80% of the cadence related components' energy from force data. This was
      done without compromising the information contained in the frequencies close to
      such notch filters. CONCLUSIONS: The presented methodology offers an effective
      cancelation of the undesired components from force data, allowing the system to
      extract in real-time voluntary user's navigation commands. Based on this real
      time identification of voluntary user's commands, a classical approach to the
      control architecture of the robotic walker is being developed, in order to obtain
      stable and safe user assisted locomotion.

PMID- 20687923
TI  - Murine leukemia virus RNA dimerization is coupled to transcription and splicing
      processes.
AB  - Most of the cell biological aspects of retroviral genome dimerization remain
      unknown. Murine leukemia virus (MLV) constitutes a useful model to study when and
      where dimerization occurs within the cell. For instance, MLV produces a
      subgenomic RNA (called SD') that is co-packaged with the genomic RNA
      predominantly as FLSD' heterodimers. This SD' RNA is generated by splicing of the
      genomic RNA and also by direct transcription of a splice-associated retroelement
      of MLV (SDARE). We took advantage of these two SD' origins to study the effects
      of transcription and splicing events on RNA dimerization. Using genetic
      approaches coupled to capture of RNA heterodimer in virions, we determined
      heterodimerization frequencies in different cellular contexts. Several cell lines
      were stably established in which SD' RNA was produced by either splicing or
      transcription from SDARE. Moreover, SDARE was integrated into the host chromosome
      either concomitantly or sequentially with the genomic provirus. Our results
      showed that transcribed genomic and SD' RNAs preferentially formed heterodimers
      when their respective proviruses were integrated together. In contrast,
      heterodimerization was strongly affected when the two proviruses were integrated
      independently. Finally, dimerization was enhanced when the transcription sites
      were expected to be physically close. For the first time, we report that splicing
      and RNA dimerization appear to be coupled. Indeed, when the RNAs underwent
      splicing, the FLSD' dimerization reached a frequency similar to co
      transcriptional heterodimerization. Altogether, our results indicate that
      randomness of heterodimerization increases when RNAs are co-expressed during
      either transcription or splicing. Our results strongly support the notion that
      dimerization occurs in the nucleus, at or near the transcription and splicing
      sites, at areas of high viral RNA concentration.

PMID- 20687922
TI  - Angiogenesis and chronic kidney disease.
AB  - The number of patients requiring renal replacement therapy due to end-stage
      renal disease (ESRD) is increasing worldwide. The prevalence of chronic kidney
      disease (CKD), and the importance of CKD as a risk factor in development of ESRD
      and in complicating cardiovascular disease (CVD) have been confirmed. In recent
      years, the involvement of angiogenesis-related factors in the progression of CKD
      has been studied, and the potential therapeutic effects on CKD of modulating
      these factors have been identified. Vascular endothelial growth factor (VEGF)-A,
      a potent pro-angiogenic factor, is involved in the development of the kidney, in
      maintenance of the glomerular capillary structure and filtration barrier, and in
      the renal repair process after injury. VEGF-A is also involved in the development
      of early diabetic nephropathy, demonstrated by the therapeutic effects of anti
      VEGF-A antibody. Angiopoietin (Ang)-1 induces the maturation of newly formed
      blood vessels, and the therapeutic effects of Ang-1 in diabetic nephropathy have
      been described. In experimental models of diabetic nephropathy, the therapeutic
      effects of angiogenesis inhibitors, including angiostatin, endostatin and
      tumstatin peptides, the isocoumarin NM-3, and vasohibin-1, have been
      reported.Further analysis of the involvement of angiogenesis-related factors in
      the development of CKD is required. Determining the disease stage at which
      therapy is most effective and developing an effective drug delivery system
      targeting the kidney will be essential for pro-or anti-angiogenic strategies for
      patients with CKD.

PMID- 20687924
TI  - The @RISK Study: Risk communication for patients with type 2 diabetes: design of
      a randomised controlled trial.
AB  - BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) have an increased risk
      to develop severe diabetes related complications, especially cardiovascular
      disease (CVD). The risk to develop CVD can be estimated by means of risk
      formulas. However, patients have difficulties to understand the outcomes of these
      formulas. As a result, they may not recognize the importance of changing
      lifestyle and taking medication in time. Therefore, it is important to develop
      risk communication methods, that will improve the patients' understanding of
      risks associated with having diabetes, which enables them to make informed
      choices about their diabetes care.The aim of this study is to investigate the
      effects of an intervention focussed on the communication of the absolute 10-year
      risk to develop CVD on risk perception, attitude and intention to change
      lifestyle behaviour in patients with T2DM. The conceptual framework of the
      intervention is based on the Theory of Planned Behaviour and the Self-regulation
      Theory. METHODS: A randomised controlled trial will be performed in the Diabetes
      Care System West-Friesland (DCS), a managed care system. Newly referred T2DM
      patients of the DCS, younger than 75 years will be eligible for the study. The
      intervention group will be exposed to risk communication on CVD, on top of
      standard managed care of the DCS. This intervention consists of a simple
      explanation on the causes and consequences of CVD, and possibilities for
      prevention. The probabilities of CVD in 10 year will be explained in natural
      frequencies and visualised by a population diagram. The control group will
      receive standard managed care. The primary outcome is appropriateness of risk
      perception. Secondary outcomes are attitude and intention to change lifestyle
      behaviour and illness perception. Differences between baseline and follow-up (2
      and 12 weeks) between groups will be analysed according to the intention-to-treat
      principle. The study was powered on 120 patients in each group. DISCUSSION: This
      innovative risk communication method based on two behavioural theories might
      improve patient's appropriateness of risk perception and attitude concerning
      lifestyle change. With a better understanding of their CVD risk, patients will be
      able to make informed choices concerning diabetes care. TRIAL REGISTRATION: The
      trial is registered as NTR1556 in the Dutch Trial Register.

PMID- 20687926
TI  - Locked volar plating for complex distal radius fractures: Patient reported
      outcomes and satisfaction.
AB  - BACKGROUND: Distal radius fractures are common. The increasing prevalence of
      osteoporosis contributes to frequently complex articular injuries sustained even
      after low energy falls. The best method of treating complex type C distal radius
      fractures is debated. Locked volar plating and external fixation are both widely
      used with good reported results. Measures of success are traditionally based on
      technical measurements or the perception of the surgeon. Patient reported
      measures of outcome are increasingly recognised as important markers of surgical
      success. We report our experience using locked volar plating for complex type C
      distal radius fractures as well as patient reported measures of success and
      satisfaction. METHODS: Over a 12 month period we treated 21 patients with type C
      distal radius fractures using locked volar plating. These patients were followed
      up for at least 12 months and the outcome was assessed using clinical
      examination, grip strength measurements, radiographs and Patient Rated Wrist
      Evaluation (PRWE) scoring. RESULTS: The 21 patients studied had an average age of
      48 years. There were 8 men and 13 women. All of the fractures had united by 3
      months. There were no cases of wound infection or tendon injury/irritation.
      Patients reported low pain scores, good patient rated wrist evaluation scores and
      high levels of satisfaction. CONCLUSIONS: Locked volar plating for complex distal
      radius fractures produces good results when assessed using patient reported
      measures of outcome. Further work should address whether locked volar plating
      offers superior outcomes and patient satisfaction compared to external fixation.

PMID- 20687925
TI  - Octamer-binding factor 6 (Oct-6/Pou3f1) is induced by interferon and contributes
      to dsRNA-mediated transcriptional responses.
AB  - BACKGROUND: Octamer-binding factor 6 (Oct-6, Pou3f1, SCIP, Tst-1) is a
      transcription factor of the Pit-Oct-Unc (POU) family. POU proteins regulate key
      developmental processes and have been identified from a diverse range of species.
      Oct-6 expression is described to be confined to the developing brain, Schwann
      cells, oligodendrocyte precursors, testes, and skin. Its function is primarily
      characterised in Schwann cells, where it is required for correctly timed
      transition to the myelinating state. In the present study, we report that Oct-6
      is an interferon (IFN)-inducible protein and show for the first time expression
      in murine fibroblasts and macrophages. RESULTS: Oct-6 was induced by type I and
      type II IFN, but not by interleukin-6. Induction of Oct-6 after IFNbeta treatment
      was mainly dependent on signal transducer and activator of transcription 1
      (Stat1) and partially on tyrosine kinase 2 (Tyk2). Chromatin immunopreciptitation
      experiments revealed binding of Stat1 to the Oct-6 promoter in a region around
      500 bp upstream of the transcription start site, a region different from the
      downstream regulatory element involved in Schwann cell-specific Oct-6 expression.
      Oct-6 was also induced by dsRNA treatment and during viral infections, in both
      cases via autocrine/paracrine actions of IFNalpha/beta. Using microarray and RT
      qPCR, we furthermore show that Oct-6 is involved in the regulation of
      transcriptional responses to dsRNA, in particular in the gene regulation of
      serine/threonine protein kinase 40 (Stk40) and U7 snRNA-associated Sm-like
      protein Lsm10 (Lsm10). CONCLUSION: Our data show that Oct-6 expression is not as
      restricted as previously assumed. Induction of Oct-6 by IFNs and viruses in at
      least two different cell types, and involvement of Oct-6 in gene regulation after
      dsRNA treatment, suggest novel functions of Oct-6 in innate immune responses.

PMID- 20687927
TI  - Prevalence of peripheral arterial disease in patients at non-high cardiovascular
      risk. Rationale and design of the PANDORA study.
AB  - BACKGROUND: Lower extremity peripheral arterial disease (PAD) is a marker of
      widespread atherosclerosis. Individuals with PAD, most of whom do not show
      typical PAD symptoms ('asymptomatic' patients), are at increased risk of
      cardiovascular ischaemic events. American College of Cardiology/American Heart
      Association guidelines recommend that individuals with asymptomatic lower
      extremity PAD should be identified by measurement of ankle-brachial index (ABI).
      However, despite its associated risk, PAD remains under-recognised by clinicians
      and the general population and office-based ABI detection is still poorly-known
      and under-used in clinical practice. The Prevalence of peripheral Arterial
      disease in patients with a non-high cardiovascular disease risk, with No overt
      vascular Diseases nOR diAbetes mellitus (PANDORA) study has a primary aim of
      assessing the prevalence of lower extremity PAD through ABI measurement, in
      patients at non-high cardiovascular risk, with no overt cardiovascular diseases
      (including symptomatic PAD), or diabetes mellitus. Secondary objectives include
      documenting the prevalence and treatment of cardiovascular risk factors and the
      characteristics of both patients and physicians as possible determinants for PAD
      under-diagnosis. METHODS/DESIGN: PANDORA is a non-interventional, cross
      sectional, pan-European study. It includes approximately 1,000 primary care
      participating sites, across six European countries (Belgium, France, Greece,
      Italy, The Netherlands, Switzerland). Investigator and patient questionnaires
      will be used to collect both right and left ABI values at rest, presence of
      cardiovascular disease risk factors, current pharmacological treatment, and
      determinants for PAD under-diagnosis. DISCUSSION: The PANDORA study will provide
      important data to estimate the prevalence of asymptomatic PAD in a population
      otherwise classified at low or intermediate risk on the basis of current risk
      scores in a primary care setting. TRIAL REGISTRATION NUMBER: Clinical Trials.gov
      Identifier: NCT00689377.

PMID- 20687928
TI  - Monozygotic twins with Neurofibromatosis type 1, concordant phenotype and
      synchronous development of MPNST and metastasis.
AB  - BACKGROUND: Neurofibromatosis type 1 is a common autosomal dominant disorder with
      full penetrance and variable expression. The condition predisposes individuals to
      the development of malignant nervous system tumours, most frequently Malignant
      Peripheral Nerve Sheath Tumours (MPNSTs). Previous studies indicate that genetic
      factors other than mutations in NF1 may be responsible for the condition's
      variable expression. CASE REPORT: Here we present data from a pair of monozygotic
      twins affected by Neurofibromatosis type 1 resulting from a de novo mutation.
      Both twins developed a left sciatic plexiform neurofibroma that evolved into
      MPNST at a similar age and they also developed pulmonary metastasis at the same
      age. Other concordant traits between the twins were: macrocephaly, psychomotor
      delay, cafe-au-lait spots, cutaneous neurofibromas, retroperitoneal, pleural and
      paraspinal neurofibromas. The main discordant features observed were tibial
      pseudoarthrosis, pectus carinatum, osteoporosis and thymus hyperplasia.
      CONCLUSIONS: This is the first report of monozygotic twins with Neurofibromatosis
      type 1 that develop MPNSTs, the localization and chronological evolution of
      which, and its metastasis, is concordant in both twins. These cases suggest that
      the events involved in the transformation of benign plexiform neurofibromas to
      MPNSTs in Neurofibromatosis type 1, follow a spatiotemporally programme that is
      influenced by heritable factors other than NF1 mutations.

PMID- 20687929
TI  - A proteogenomic update to Yersinia: enhancing genome annotation.
AB  - BACKGROUND: Modern biomedical research depends on a complete and accurate
      proteome. With the widespread adoption of new sequencing technologies, genome
      sequences are generated at a near exponential rate, diminishing the time and
      effort that can be invested in genome annotation. The resulting gene set contains
      numerous errors in even the most basic form of annotation: the primary structure
      of the proteins. RESULTS: The application of experimental proteomics data to
      genome annotation, called proteogenomics, can quickly and efficiently discover
      misannotations, yielding a more accurate and complete genome annotation. We
      present a comprehensive proteogenomic analysis of the plague bacterium, Yersinia
      pestis KIM. We discover non-annotated genes, correct protein boundaries, remove
      spuriously annotated ORFs, and make major advances towards accurate
      identification of signal peptides. Finally, we apply our data to 21 other
      Yersinia genomes, correcting and enhancing their annotations. CONCLUSIONS: In
      total, 141 gene models were altered and have been updated in RefSeq and Genbank,
      which can be accessed seamlessly through any NCBI tool (e.g. blast) or downloaded
      directly. Along with the improved gene models we discover new, more accurate
      means of identifying signal peptides in proteomics data.

PMID- 20687930
TI  - Breast tumor kinase and extracellular signal-regulated kinase 5 mediate Met
      receptor signaling to cell migration in breast cancer cells.
AB  - INTRODUCTION: Breast tumor kinase (Brk/protein tyrosine kinase 6 (PTK6)) is a
      nonreceptor, soluble tyrosine kinase overexpressed in the majority of breast
      tumors. Previous work has placed Brk downstream of epidermal growth factor
      receptor (ErbB) activation and upstream of extracellular signal-regulated kinase
      5 (ERK5) and p38 mitogen-activated protein (MAP) kinases. Herein we investigate
      the regulation of Brk kinase activity and cell migration in response to treatment
      of keratinocytes (HaCaT cells) and breast cancer cell lines (MDA-MB-231 and T47D
      cells) with hepatocyte growth factor (HGF) and macrophage stimulating protein
      (MSP), peptide ligands for Met and Ron receptors, respectively. METHODS: In vitro
      kinase assays were performed to directly measure Brk kinase activity in response
      to MET and RON ligands. Transfection of Brk-targeted RNAi was used to knock down
      endogenous Brk or ERK5 in multiple cell lines. Kinase activities (downstream of
      MET signaling) were assayed by Western blotting using total and phospho-specific
      antibodies. Boyden chamber assays were used to measure cell migration in response
      to manipulation of Brk and downstream MET effectors. Rescue experiments were
      performed by knock down of endogenous Brk using RNAi (targeting the untranslated
      region (3'-UTR)) and transient transfection (re-expression) of either wild-type
      or kinase-inactive Brk. RESULTS: Brk gene silencing revealed that HGF, but not
      MSP, induced robust Brk-dependent cell migration. Brk and ERK5 copurified in HGF
      induced protein complexes, and Brk/ERK5 complexes formed independently of Brk
      kinase activity. ERK5 was required for breast cancer cell but not keratinocyte
      cell migration, which became ERK1/2-dependent upon ERK5 knockdown. Notably,
      rescue experiments indicated that the kinase activity of Brk was not required for
      HGF-induced cell migration. Further, expression of either wild-type or kinase
      inactive Brk in Brk-null MDA-MB-435 cells activated ERK5 and conferred increased
      HGF-induced cell migration. CONCLUSIONS: These results have identified Brk and
      ERK5 as important downstream effectors of Met signaling to cell migration.
      Targeting ERK5 kinase activity or inhibiting the formation of Brk/ERK5 complexes
      may provide an additional means of blocking cell migration associated with breast
      cancer progression to metastasis.

PMID- 20687932
TI  - Reorganizing pediatric rehabilitation services to improve accessibility: do we
      sacrifice quality?
AB  - BACKGROUND: The impact of a pediatric rehabilitation service delivery
      reorganization to improve access to services on parents' and service providers'
      perception of service quality was evaluated. Child-, family-, service- and
      service provider-related characteristics possibly associated with these
      perceptions were explored. METHODS: Perceptions were measured using the Measure
      of Processes of Care tools and open ended questions before (2007), during (2008)
      and following (2009) service reorganization. Child and family characteristics,
      services received and service provider data were documented. Mean MPOC scores
      were compared over time (ANOVAs and Generalized Estimating Equations) and t
      tests, correlations and ANOVAs determined whether the characteristics influenced
      scores. RESULTS: Families' (n = 222) and service providers' (n = 129) perceptions
      of quality were high in 2007 (3.67 to 6.31/7) and remained high over the next 2
      years (p >or= 0.16). Two MPOC domain scores (Respectful care and Providing
      general information) were consistently scored the highest (mean >or= 5.66/7) and
      the lowest (mean <or= 4.75/7), respectively. Families with more education and
      those with children 12-21 years old tended to attribute lower MPOC scores.
      Participants were generally satisfied with the new service model and
      recommendations included improving information exchange. CONCLUSIONS: Results
      suggest that it is possible to reorganize pediatric rehabilitation services while
      maintaining quality.

PMID- 20687933
TI  - Prevalence of mood and anxiety disorder in self reported irritable bowel syndrome
      (IBS). An epidemiological population based study of women.
AB  - BACKGROUND: Irritable bowel syndrome (IBS) is commonly regarded as a functional
      disorder, and is hypothesized to be associated with anxiety and depression. This
      evidence mainly rests on population-based studies utilising self-report screening
      instruments for psychopathology. Other studies applying structured clinical
      interviews are generally based on small clinical samples, which are vulnerable to
      biases. The extant evidence base for an association between IBS and
      psychopathology is hence not conclusive. The aim of this study was therefore to
      re-examine the hypothesis using population-based data and psychiatric morbidity
      established with a structured clinical interview. METHODS: Data were derived from
      a population-based epidemiological study (n = 1077). Anxiety and mood disorders
      were established using the Structured Clinical Interview for DSM-IV-TR (SCID
      I/NP) and the General Health Questionnaire (GHQ-12). Current and lifetime IBS was
      self-reported. Hypertension and diabetes were employed as comparison groups as
      they are expected to be unrelated to mental health. RESULTS: Current IBS (n = 69,
      6.4%) was associated with an increased likelihood of current mood and/or anxiety
      disorders (OR = 2.62, 95%CI 1.49 - 4.60). Half the population reporting a
      lifetime IBS diagnosis also had a lifetime mood or anxiety disorder. Exploratory
      analyses demonstrated an increased prevalence of IBS across most common anxiety
      and mood disorders, the exception being bipolar disorder. The association with
      IBS and symptoms load (GHQ-12) followed a curved dose response pattern. In
      contrast, hypertension and diabetes were consistently unrelated to psychiatric
      morbidity. CONCLUSIONS: IBS is significantly associated with anxiety and mood
      disorders. This study provides indicative evidence for IBS as a disorder with a
      psychosomatic aspect.

PMID- 20687931
TI  - Rationale and design of the Kanyini guidelines adherence with the polypill
      (Kanyini-GAP) study: a randomised controlled trial of a polypill-based strategy
      amongst indigenous and non indigenous people at high cardiovascular risk.
AB  - BACKGROUND: The Kanyini Guidelines Adherence with the Polypill (Kanyini-GAP)
      Study aims to examine whether a polypill-based strategy (using a single capsule
      containing aspirin, a statin and two blood pressure-lowering agents) amongst
      Indigenous and non-Indigenous people at high risk of experiencing a
      cardiovascular event will improve adherence to guideline-indicated therapies, and
      lower blood pressure and cholesterol levels. METHODS/DESIGN: The study is an
      open, randomised, controlled, multi-centre trial involving 1000 participants at
      high risk of cardiovascular events recruited from mainstream general practices
      and Aboriginal Medical Services, followed for an average of 18 months. The
      participants will be randomised to one of two versions of the polypill, the
      version chosen by the treating health professional according to clinical features
      of the patient, or to usual care. The primary study outcomes will be changes,
      from baseline measures, in serum cholesterol and systolic blood pressure and self
      reported current use of aspirin, a statin and at least two blood pressure
      lowering agents. Secondary study outcomes include cardiovascular events, renal
      outcomes, self-reported barriers to indicated therapy, prescription of indicated
      therapy, occurrence of serious adverse events and changes in quality-of-life. The
      trial will be supplemented by formal economic and process evaluations.
      DISCUSSION: The Kanyini-GAP trial will provide new evidence as to whether or not
      a polypill-based strategy improves adherence to effective cardiovascular
      medications amongst individuals in whom these treatments are indicated. TRIAL
      REGISTRATION: This trial is registered with the Australian New Zealand Clinical
      Trial Registry ACTRN126080005833347.

PMID- 20687934
TI  - Adrenocortical carcinosarcoma: a case report and review of the literature.
AB  - Adrenocortical carcinosarcoma is an extremely rare and aggressive variant of
      adrenocortical carcinoma characterized by the presence of both carcinomatous and
      sarcomatous components, with the latter often showing heterologous
      differentiation. Due to the rarity and unusual histology, it may pose a
      diagnostic challenge. In order to increase awareness and identify potential
      diagnostic pitfalls, we report the ninth case of non-functioning adrenocortical
      carcinosarcoma in a 45-year-old man who presented with worsening epigastric pain
      and a left large retroperitoneal mass in close proximity to the body/tail of
      pancreas and third portion of the duodenum with displacement of the kidney
      without parenchymal invasion and multiple liver nodules detected by computed
      tomographic scan. On en bloc resection, the tumor grossly did not involve the
      pancreas, kidney or colon. Histologically, the tumor was composed of two distinct
      components - an epithelioid component with granular cytoplasm that stained for
      synaptophysin, Melan-A, calretinin, and vimentin compatible with adrenocortical
      differentiation, and a pleomorphic to spindled component that was positive for
      desmin and myogenin, compatible with rhabdomyosarcomatous differentiation. A
      wedge biopsy of a liver nodule showed morphologic features similar to the
      epithelial component of the primary tumor. The patient died three months after
      surgery due to locoregional and distant recurrence. Adrenocortical carcinosarcoma
      is a rare malignancy that adds to the differential diagnostic considerations for
      a retroperitoneal epithelioid malignancy. Awareness of this as a possibility will
      help in distinguishing this tumor from other carcinomas, melanomas, and true
      sarcomas.

PMID- 20687935
TI  - Are adolescents with high socioeconomic status more likely to engage in alcohol
      and illicit drug use in early adulthood?
AB  - BACKGROUND: Previous literature has shown a divergence by age in the relationship
      between socioeconomic status (SES) and substance use: adolescents with low SES
      are more likely to engage in substance use, as are adults with high SES. However,
      there is growing evidence that adolescents with high SES are also at high risk
      for substance abuse. The objective of this study is to examine this relationship
      longitudinally, that is, whether wealthier adolescents are more likely than those
      with lower SES to engage in substance use in early adulthood. METHODS: The study
      analyzed data from the National Longitudinal Survey of Adolescent Health
      (AddHealth), a longitudinal, nationally-representative survey of secondary school
      students in the United States. Logistic regression models were analyzed examining
      the relationship between adolescent SES (measured by parental education and
      income) and substance use in adulthood, controlling for substance use in
      adolescence and other covariates. RESULTS: Higher parental education is
      associated with higher rates of binge drinking, marijuana and cocaine use in
      early adulthood. Higher parental income is associated with higher rates of binge
      drinking and marijuana use. No statistically significant results are found for
      crystal methamphetamine or other drug use. Results are not sensitive to the
      inclusion of college attendance by young adulthood as a sensitivity analysis.
      However, when stratifying by race, results are consistent for white non
      Hispanics, but no statistically significant results are found for non-whites.
      This may be a reflection of the smaller sample size of non-whites, but may also
      reflect that these trends are driven primarily by white non-Hispanics.
      CONCLUSIONS: Previous research shows numerous problems associated with substance
      use in young adults, including problems in school, decreased employment,
      increases in convictions of driving under the influence (DUI) and accidental
      deaths. Much of the previous literature is focused on lower SES populations.
      Therefore, it is possible that teachers, parents and school administrators in
      wealthier schools may not perceive as great to address substance abuse treatment
      in their schools. This study can inform teachers, parents, school administrators
      and program officials of the need for addressing drug abuse prevention activities
      to this population of students.

PMID- 20687936
TI  - Structural features in the Rous sarcoma virus RNA stability element are necessary
      for sensing the correct termination codon.
AB  - BACKGROUND: Nonsense-mediated mRNA decay (NMD) is an mRNA quality control
      mechanism that selectively recognizes and targets for degradation mRNAs
      containing premature termination codons. Retroviral full-length RNA is presented
      to the host translation machinery with characteristics rarely observed among host
      cell mRNAs: a long 3' UTR, retained introns, and multiple open reading frames. As
      a result, the viral RNA is predicted to be recognized by the host NMD machinery
      and degraded. In the case of the Rous sarcoma virus (RSV), we identified a
      stability element (RSE), which resides immediately downstream of the gag
      termination codon and facilitates NMD evasion. RESULTS: We defined key RNA
      features of the RSE through directed mutagenesis of the virus. These data suggest
      that the minimal RSE is 155 nucleotides (nts) and functions independently of the
      nucleotide sequence of the stop codon or the first nucleotide following the stop
      codon. Further data suggested that the 3'UTRs of the RSV pol and src may also
      function as stability elements. CONCLUSIONS: We propose that these stability
      elements in RSV may be acting as NMD insulators to mask the preceding stop codon
      from the NMD machinery.

PMID- 20687937
TI  - Genome-wide DNA methylation analysis for diabetic nephropathy in type 1 diabetes
      mellitus.
AB  - BACKGROUND: Diabetic nephropathy is a serious complication of diabetes mellitus
      and is associated with considerable morbidity and high mortality. There is
      increasing evidence to suggest that dysregulation of the epigenome is involved in
      diabetic nephropathy. We assessed whether epigenetic modification of DNA
      methylation is associated with diabetic nephropathy in a case-control study of
      192 Irish patients with type 1 diabetes mellitus (T1D). Cases had T1D and
      nephropathy whereas controls had T1D but no evidence of renal disease. METHODS:
      We performed DNA methylation profiling in bisulphite converted DNA from cases and
      controls using the recently developed Illumina Infinium HumanMethylation27
      BeadChip, that enables the direct investigation of 27,578 individual cytosines at
      CpG loci throughout the genome, which are focused on the promoter regions of
      14,495 genes. RESULTS: Singular Value Decomposition (SVD) analysis indicated that
      significant components of DNA methylation variation correlated with patient age,
      time to onset of diabetic nephropathy, and sex. Adjusting for confounding factors
      using multivariate Cox-regression analyses, and with a false discovery rate (FDR)
      of 0.05, we observed 19 CpG sites that demonstrated correlations with time to
      development of diabetic nephropathy. Of note, this included one CpG site located
      18 bp upstream of the transcription start site of UNC13B, a gene in which the
      first intronic SNP rs13293564 has recently been reported to be associated with
      diabetic nephropathy. CONCLUSION: This high throughput platform was able to
      successfully interrogate the methylation state of individual cytosines and
      identified 19 prospective CpG sites associated with risk of diabetic nephropathy.
      These differences in DNA methylation are worthy of further follow-up in
      replication studies using larger cohorts of diabetic patients with and without
      nephropathy.

PMID- 20687938
TI  - Validation study of a web-based assessment of functional recovery after radical
      prostatectomy.
AB  - BACKGROUND: Good clinical care of prostate cancer patients after radical
      prostatectomy depends on careful assessment of post-operative morbidities, yet
      physicians do not always judge patient symptoms accurately. Logistical problems
      associated with using paper questionnaire limit their use in the clinic. We have
      implemented a web-interface ("STAR") for patient-reported outcomes after radical
      prostatectomy. METHODS: We analyzed data on the first 9 months of clinical
      implementation to evaluate the validity of the STAR questionnaire to assess
      functional outcomes following radical prostatectomy. We assessed response rate,
      internal consistency within domains, and the association between survey responses
      and known predictors of sexual and urinary function, including age, time from
      surgery, nerve sparing status and co-morbidities. RESULTS: Of 1581 men sent an
      invitation to complete the instrument online, 1235 responded for a response rate
      of 78%. Cronbach's alpha was 0.84, 0.86 and 0.97 for bowel, urinary and sexual
      function respectively. All known predictors of sexual and urinary function were
      significantly associated with survey responses in the hypothesized direction.
      CONCLUSIONS: We have found that web-based assessment of functional recovery after
      radical prostatectomy is practical and feasible. The instrument demonstrated
      excellent psychometric properties, suggested that validity is maintained when
      questions are transferred from paper to electronic format and when patients give
      responses that they know will be seen by their doctor and added to their clinic
      record. As such, our system allows ready implementation of patient-reported
      outcomes into routine clinical practice.

PMID- 20687939
TI  - Co-expressed immune and metabolic genes in visceral and subcutaneous adipose
      tissue from severely obese individuals are associated with plasma HDL and glucose
      levels: a microarray study.
AB  - BACKGROUND: Excessive accumulation of body fat, in particular in the visceral fat
      depot, is a major risk factor to develop a variety of diseases such as type 2
      diabetes. The mechanisms underlying the increased risk of obese individuals to
      develop co-morbid diseases are largely unclear.We aimed to identify genes
      expressed in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT)
      that are related to blood parameters involved in obesity co-morbidity, such as
      plasma lipid and glucose levels, and to compare gene expression between the fat
      depots. METHODS: Whole-transcriptome SAT and VAT gene expression levels were
      determined in 75 individuals with a BMI >35 kg/m2. Modules of co-expressed genes
      likely to be functionally related were identified and correlated with BMI, plasma
      levels of glucose, insulin, HbA1c, triglycerides, non-esterified fatty acids,
      ALAT, ASAT, C-reactive protein, and LDL- and HDL cholesterol. RESULTS: Of the
      approximately 70 modules identified in SAT and VAT, three SAT modules were
      inversely associated with plasma HDL-cholesterol levels, and a fourth module was
      inversely associated with both plasma glucose and plasma triglyceride levels (p <
      5.33 x 10(-5)). These modules were markedly enriched in immune and metabolic
      genes. In VAT, one module was associated with both BMI and insulin, and another
      with plasma glucose (p < 4.64 x 10(-5)). This module was also enriched in
      inflammatory genes and showed a marked overlap in gene content with the SAT
      modules related to HDL. Several genes differentially expressed in SAT and VAT
      were identified. CONCLUSIONS: In obese subjects, groups of co-expressed genes
      were identified that correlated with lipid and glucose metabolism parameters;
      they were enriched with immune genes. A number of genes were identified of which
      the expression in SAT correlated with plasma HDL cholesterol, while their
      expression in VAT correlated with plasma glucose. This underlines both the
      singular importance of these genes for lipid and glucose metabolism and the
      specific roles of these two fat depots in this respect.

PMID- 20687941
TI  - Free radicals produced by the oxidation of gallic acid: An electron paramagnetic
      resonance study.
AB  - BACKGROUND: Gallic acid (3,4,5-trihydroxybenzoic acid) is found in a wide variety
      of plants; it is extensively used in tanning, ink dyes, as well as in the
      manufacturing of paper. The gallate moiety is a key component of many functional
      phytochemicals. In this work electron paramagnetic spectroscopy (EPR) was used to
      detect the free radicals generated by the air-oxidation of gallic acid. RESULTS:
      We found that gallic acid produces two different radicals as a function of pH. In
      the pH range between 7-10, the spectrum of the gallate free radical is a doublet
      of triplets (aH = 1.00 G, aH = 0.23 G, aH = 0.28 G). This is consistent with
      three hydrogens providing hyperfine splitting. However, in a more alkaline
      environment, pH >10, the hyperfine splitting pattern transforms into a 1:2:1
      pattern (aH (2) = 1.07 G). Using D2O as a solvent, we demonstrate that the third
      hydrogen (i.e. aH = 0.28 G) at lower pH is a slowly exchanging hydron,
      participating in hydrogen bonding with two oxygens in ortho position on the
      gallate ring. The pKa of this proton has been determined to be 10. CONCLUSIONS:
      This simple and novel approach permitted the understanding of the prototropic
      equilibrium of the semiquinone radicals generated by gallic acid, a ubiquitous
      compound, allowing new insights into its oxidation and subsequent reactions.

PMID- 20687940
TI  - Protocol for work place adjusted intelligent physical exercise reducing
      musculoskeletal pain in shoulder and neck (VIMS): a cluster randomized controlled
      trial.
AB  - BACKGROUND: Neck and shoulder complaints are common among employees in sedentary
      occupations characterized by intensive computer use. Specific strength training
      is a promising type of physical exercise for relieving neck and shoulder pain in
      office workers. However, the optimal combination of frequency and exercise
      duration, as well as the importance of exercise supervision, is unknown. The VIMS
      study investigates in a cluster randomized controlled design the effectiveness of
      different time wise combinations of specific strength training with identical
      accumulated volume, and the relevance of training supervision for safe and
      effective training. METHODS/DESIGN: A cluster randomized controlled trial of 20
      weeks duration where employed office workers are randomized to 1 x 60 min, 3 x 20
      min, 9 x 7 min per week of specific strength training with training supervision,
      to 3 x 20 min per week of specific strength training with a minimal amount of
      training supervision, or to a reference group without training. A questionnaire
      will be sent to 2000 employees in jobs characterized by intensive computer work.
      Employees with cardiovascular disease, trauma, hypertension, or serious chronic
      disease will be excluded. The main outcome measure is pain in the neck and
      shoulders at week 20. TRIAL REGISTRATION: The trial is registered at
      ClinicalTrials.gov, number NCT01027390.

PMID- 20687942
TI  - Model-based extension of high-throughput to high-content data.
AB  - BACKGROUND: High-quality quantitative data is a major limitation in systems
      biology. The experimental data used in systems biology can be assigned to one of
      the following categories: assays yielding average data of a cell population, high
      content single cell measurements and high-throughput techniques generating single
      cell data for large cell populations. For modeling purposes, a combination of
      data from different categories is highly desirable in order to increase the
      number of observable species and processes and thereby maximize the
      identifiability of parameters. RESULTS: In this article we present a method that
      combines the power of high-content single cell measurements with the efficiency
      of high-throughput techniques. A calibration on the basis of identical cell
      populations measured by both approaches connects the two techniques. We develop a
      mathematical model to relate quantities exclusively observable by high-content
      single cell techniques to those measurable with high-content as well as high
      throughput methods. The latter are defined as free variables, while the variables
      measurable with only one technique are described in dependence of those. It is
      the combination of data calibration and model into a single method that makes it
      possible to determine quantities only accessible by single cell assays but using
      high-throughput techniques. As an example, we apply our approach to the
      nucleocytoplasmic transport of STAT5B in eukaryotic cells. CONCLUSIONS: The
      presented procedure can be generally applied to systems that allow for dividing
      observables into sets of free quantities, which are easily measurable, and
      variables dependent on those. Hence, it extends the information content of high
      throughput methods by incorporating data from high-content measurements.

PMID- 20687943
TI  - RNA-Seq Atlas of Glycine max: a guide to the soybean transcriptome.
AB  - BACKGROUND: Next generation sequencing is transforming our understanding of
      transcriptomes. It can determine the expression level of transcripts with a
      dynamic range of over six orders of magnitude from multiple tissues,
      developmental stages or conditions. Patterns of gene expression provide insight
      into functions of genes with unknown annotation. RESULTS: The RNA Seq-Atlas
      presented here provides a record of high-resolution gene expression in a set of
      fourteen diverse tissues. Hierarchical clustering of transcriptional profiles for
      these tissues suggests three clades with similar profiles: aerial, underground
      and seed tissues. We also investigate the relationship between gene structure and
      gene expression and find a correlation between gene length and expression.
      Additionally, we find dramatic tissue-specific gene expression of both the most
      highly-expressed genes and the genes specific to legumes in seed development and
      nodule tissues. Analysis of the gene expression profiles of over 2,000 genes with
      preferential gene expression in seed suggests there are more than 177 genes with
      functional roles that are involved in the economically important seed filling
      process. Finally, the Seq-atlas also provides a means of evaluating existing gene
      model annotations for the Glycine max genome. CONCLUSIONS: This RNA-Seq atlas
      extends the analyses of previous gene expression atlases performed using
      Affymetrix GeneChip technology and provides an example of new methods to
      accommodate the increase in transcriptome data obtained from next generation
      sequencing. Data contained within this RNA-Seq atlas of Glycine max can be
      explored at http://www.soybase.org/soyseq.

PMID- 20687944
TI  - Validating an infrared thermal switch as a novel access technology.
AB  - BACKGROUND: Recently, a novel single-switch access technology based on infrared
      thermography was proposed. The technology exploits the temperature differences
      between the inside and surrounding areas of the mouth as a switch trigger,
      thereby allowing voluntary switch activation upon mouth opening. However, for
      this technology to be clinically viable, it must be validated against a gold
      standard switch, such as a chin switch, that taps into the same voluntary motion.
      METHODS: In this study, we report an experiment designed to gauge the concurrent
      validity of the infrared thermal switch. Ten able-bodied adults participated in a
      series of 3 test sessions where they simultaneously used both an infrared thermal
      and conventional chin switch to perform multiple trials of a number
      identification task with visual, auditory and audiovisual stimuli. Participants
      also provided qualitative feedback about switch use. User performance with the
      two switches was quantified using an efficiency measure based on mutual
      information. RESULTS: User performance (p = 0.16) and response time (p = 0.25)
      with the infrared thermal switch were comparable to those of the gold standard.
      Users reported preference for the infrared thermal switch given its non-contact
      nature and robustness to changes in user posture. CONCLUSIONS: Thermal infrared
      access technology appears to be a valid single switch alternative for individuals
      with disabilities who retain voluntary mouth opening and closing.

PMID- 20687945
TI  - Simplifying the detection of MUTYH mutations by high resolution melting analysis.
AB  - BACKGROUND: MUTYH-associated polyposis (MAP) is a disorder caused by bi-allelic
      germline MUTYH mutation, characterized by multiple colorectal adenomas. In order
      to identify mutations in MUTYH gene we applied High Resolution Melting (HRM)
      genotyping. HRM analysis is extensively employed as a scanning method for the
      detection of heterozygous mutations. Therefore, we applied HRM to show
      effectiveness in detecting homozygous mutations for these clinically important
      and frequent patients. METHODS: In this study, we analyzed phenotype and genotype
      data from 82 patients, with multiple (> or = 10) synchronous (19/82) or
      metachronous (63/82) adenomas and negative APC study (except one case). Analysis
      was performed by HRM-PCR and direct sequencing, in order to identify mutations in
      MUTYH exons 7, 12 and 13, where the most prevalent mutations are located. In
      monoallelic mutation carriers, we evaluated entire MUTYH gene in search of
      another possible alteration. HRM-PCR was performed with strict conditions in
      several rounds: the first one to discriminate the heteroduplex patterns and
      homoduplex patterns and the next ones, in order to refine and confirm parameters.
      The genotypes obtained were correlated to phenotypic features (number of adenomas
      (synchronous or metachronous), colorectal cancer (CRC) and family history).
      RESULTS: MUTYH germline mutations were found in 15.8% (13/82) of patients. The
      hot spots, Y179C (exon 7) and G396D (exon 13), were readily identified and other
      mutations were also detected. Each mutation had a reproducible melting profile by
      HRM, both heterozygous mutations and homozygous mutations. In our study of 82
      patients, biallelic mutation is associated with being a carrier of >/=10
      synchronous polyps (p = 0.05) and there is no association between biallelic
      mutation and CRC (p = 0.39) nor family history (p = 0.63). G338H non-pathogenic
      polymorphism (exon 12) was found in 23.1% (19/82) of patients. In all cases there
      was concordance between HRM (first and subsequent rounds) and sequencing data.
      CONCLUSIONS: Here, we describe a screening method, HRM, for the detection of both
      heterozygous and homozygous mutations in the gene encoding MUTYH in selected
      samples of patients with phenotype of MAP. We refine the capabilities of HRM-PCR
      and apply it to a gene not yet analyzed by this tool. As clinical decisions will
      increasingly rely on molecular medicine, the power of identifying germline
      mutations must be continuously evaluated and improved.

PMID- 20687946
TI  - Health in the 'hidden population' of people with low literacy. A systematic
      review of the literature.
AB  - BACKGROUND: Much of the evidence of an association between low functional or
      health literacy and poor health comes from studies that include people who have
      various cognitive difficulties or who do not speak the dominant language of their
      society. Low functional or health literacy among these people is likely to be
      evident in spoken conversation. However, many other people can talk readily about
      health and other issues but have problems using written information.
      Consequently, their difficulties may be far less evident to healthcare
      professionals, creating a 'hidden population' whose functional or health literacy
      problems have different implications because they are less likely to be
      recognised and addressed.We aimed to review published research to investigate
      relationships between low functional or health literacy and health in working age
      adults who can converse in the dominant language but have difficulty with written
      language. METHODS: We searched reviews and electronic databases for studies that
      examined health-related outcomes among the population of interest. We
      systematically extracted data relating to relationships between low functional or
      health literacy and both health status and various possible mediators or
      moderators of the implications of literacy for health. We developed a narrative
      review. RESULTS: Twenty-four studies met our inclusion criteria. Lower functional
      or health literacy in this population was found to be associated with worse
      health status. This may be mediated by difficulties accessing healthcare, and
      poorer self-management of health problems. It is currently unclear whether, how
      or to what extent these difficulties are mediated by poorer knowledge stemming
      from low functional or health literacy. The variation in functional or health
      literacy measures and comparisons make it difficult to compare study findings and
      to establish the implications of different literacy issues for health outcomes.
      CONCLUSIONS: There is evidence in the literature that low functional or health
      literacy is associated with poor health in the 'hidden population' of adults
      whose literacy difficulties may not be evident to health care providers. Further
      research is needed to help understand the particular disadvantages faced by this
      population and to establish appropriate responses.

PMID- 20687947
TI  - Continuing or adding IL-2 in patients treated with antiretroviral therapy (ACTG
      Protocol A5051, a rollover trial of ACTG Protocol A328).
AB  - BACKGROUND: Effective antiretroviral therapy reduces HIV-1 RNA levels, improves
      CD4 T-cell counts, and lowers the risk of opportunistic infections and
      malignancies. Interleukin-2 (IL-2) has been shown to increase CD4 T-cell numbers
      mainly by expanding CD4 cells and by prolonging their half-lives. HIV-infected
      patients previously enrolled into A328 had been randomized to antiretroviral
      therapy (ART) alone or ART followed by IL-2. In A5051, 53 patients from A328 who
      had previously received IL-2 were allowed to continue IL-2 for an additional 80
      weeks; 27 patients who had received ART alone received IL-2 for 80 weeks.
      RESULTS: The patients previously receiving IL-2 continued to have elevated CD4
      levels with extended use of IL-2. The prior ART-alone recipients had increases in
      CD4 levels to comparable levels as the prior IL-2 recipients (median 804 versus
      847 cells/mm3 at week 72; 60% versus 9% had >50% increase in A5051 to week 72, p
      < 0.001). Those who had previously received IL-2 required fewer IL-2 cycles to
      maintain their CD4 T-cell counts compared to those newly initiating IL-2. The
      treatments were well tolerated with no significant differences in toxicity or
      discontinuations between those newly versus previously receiving IL-2. There were
      few clinical events observed. CONCLUSIONS: Although sustained CD4 T-cell count
      increases were seen with IL-2 administration as in other studies, the absence of
      clinical benefit in two recent randomized trials has demonstrated no apparent
      role for IL-2 as a therapy in HIV disease. TRIAL REGISTRATION: A5051
      ClinicalTrials.gov Identifier: NCT00000923.

PMID- 20687948
TI  - Effects of moxibustion for constipation treatment: a systematic review of
      randomized controlled trials.
AB  - Several studies reported that moxibustion was effective in treating
      constipation. This systematic review assesses the clinical evidence for or
      against moxibustion for treating constipation. Twelve databases were searched
      from their inception to March 2010. Only randomized clinical trials (RCTs) were
      included if they compared moxibustion with placebo, sham treatment, drug therapy
      or no treatment. The methodological quality of these RCTs was assessed with the
      Cochrane risk of bias analysis. All three RCTs included in the study had a high
      risk of bias. Two included studies found favorable effects of moxibustion. The
      third RCT showed significant effects in the moxibustion group. Given that the
      methodological quality of all RCTs was poor, the results from the present review
      are insufficient to suggest that moxibustion is an effective treatment for
      constipation. More rigorous studies are warranted.

PMID- 20687949
TI  - Bilateral somatosensory evoked potentials following intermittent theta-burst
      repetitive transcranial magnetic stimulation.
AB  - BACKGROUND: Intermittent theta-burst stimulation (iTBS) is a form of repetitive
      transcranial magnetic stimulation that may alter cortical excitability in the
      primary somatosensory cortex (SI). The present study investigated the effects of
      iTBS on subcortical and early cortical somatosensory evoked potentials (SEPs)
      recorded over left, iTBS stimulated SI and the right-hemisphere non-stimulated
      SI. SEPs were recorded before and at 5, 15, and 25 minutes following iTBS.
      RESULTS: Compared to pre-iTBS, the amplitude of cortical potential N20/P25 was
      significantly increased for 5 minutes from non-stimulated SI and for 15 to 25
      minutes from stimulated SI. Subcortical potentials recorded bilaterally remained
      unaltered following iTBS. CONCLUSION: We conclude that iTBS increases the
      cortical excitability of SI bilaterally and does not alter thalamocortical
      afferent input to SI. ITBS may provide one avenue to induce cortical plasticity
      in the somatosensory cortex.

PMID- 20687950
TI  - MLTreeMap--accurate Maximum Likelihood placement of environmental DNA sequences
      into taxonomic and functional reference phylogenies.
AB  - BACKGROUND: Shotgun sequencing of environmental DNA is an essential technique for
      characterizing uncultivated microbes in situ. However, the taxonomic and
      functional assignment of the obtained sequence fragments remains a pressing
      problem. RESULTS: Existing algorithms are largely optimized for speed and
      coverage; in contrast, we present here a software framework that focuses on a
      restricted set of informative gene families, using Maximum Likelihood to assign
      these with the best possible accuracy. This framework ('MLTreeMap';
      http://mltreemap.org/) uses raw nucleotide sequences as input, and includes hand
      curated, extensible reference information. CONCLUSIONS: We discuss how we
      validated our pipeline using complete genomes as well as simulated and actual
      environmental sequences.

PMID- 20687951
TI  - Excessive recreational computer use and food consumption behaviour among
      adolescents.
AB  - INTRODUCTION: Using the 2005 California Health Interview Survey (CHIS) data, we
      explore the association between excessive recreational computer use and specific
      food consumption behavior among California's adolescents aged 12-17. METHOD: The
      adolescent component of CHIS 2005 measured the respondents' average number of
      hours spent on viewing TV on a weekday, the average number of hours spent on
      viewing TV on a weekend day, the average number of hours spent on playing with a
      computer on a weekday, and the average number of hours spent on playing with
      computers on a weekend day. We recode these four continuous variables into four
      variables of "excessive media use," and define more than three hours of using a
      medium per day as "excessive." These four variables are then used in logistic
      regressions to predict different food consumption behaviors on the previous day:
      having fast food, eating sugary food more than once, drinking sugary drinks more
      than once, and eating more than five servings of fruits and vegetables. We use
      the following variables as covariates in the logistic regressions: age, gender,
      race/ethnicity, parental education, household poverty status, whether born in the
      U.S., and whether living with two parents. RESULTS: Having fast food on the
      previous day is associated with excessive weekday TV viewing (O.R.=1.38, p<0.01).
      Having sugary food more than once is associated with excessive weekend TV viewing
      (O.R.=1.50, p<0.001). Having sugary drinks more than once is associated with
      excessive weekday TV viewing (O.R.=1.41, p<0.01), excessive weekday recreational
      computer use (O.R.=1.38, p<0.05), and excessive weekend TV viewing (O.R.=1.43,
      p<0.001). Finally, having more than five servings of fruits and vegetables on the
      previous day is negatively associated with all four media use variables:
      excessive weekday TV viewing (O.R.=0.64, p<0.001), excessive weekday recreational
      computer use (O.R.=0.68, p<0.01), excessive weekend TV viewing (O.R.=0.80,
      p<0.05), and excessive weekend recreational computer use (O.R.=0.78, p<0.05).
      CONCLUSION: Excessive recreational computer use independently predicts
      undesirable eating behaviors that could lead to overweight and obesity.
      Preventive measures ranging from parental/youth counseling to content regulations
      might be addressing the potential undesirable influence from excessive computer
      use on eating behaviors among children and adolescents.

PMID- 20687952
TI  - Public views on a wait time management initiative: a matter of communication.
AB  - BACKGROUND: Many countries have tried to reduce waiting times for health care
      through formal wait time reduction strategies. Our paper describes views of
      members of the public about a wait time management initiative--the Ontario Wait
      Time Strategy (OWTS) (Canada). Scholars and governmental reports have advocated
      for increased public involvement in wait time management. We provide empirically
      derived recommendations for public engagement in a wait time management
      initiative. METHODS: Two qualitative studies: 1) an analysis of all emails sent
      by the public to the (OWTS) email address; and 2) in-depth interviews with
      members of the Ontario public. RESULTS: Email correspondents and interview
      participants supported the intent of the OWTS. However they wanted more
      information about the Strategy and its actions. Interview participants did not
      feel they were sufficiently made aware of the Strategy and email correspondents
      requested additional information beyond what was offered on the Strategy's
      website. Moreover, the email correspondents believed that some of the information
      that was provided on the Strategy's website and through the media was inaccurate,
      misleading, and even dishonest. Interview participants strongly supported public
      involvement in the OWTS priority setting. CONCLUSIONS: Findings suggest the
      public wanted increased communication from and with the OWTS. Effective
      communication can facilitate successful public engagement, and in turn fair and
      legitimate priority setting. Based on the study's findings we developed concrete
      recommendations for improving public involvement in wait time management.

PMID- 20687953
TI  - Lotus leaf extract and L-carnitine influence different processes during the
      adipocyte life cycle.
AB  - BACKGROUND: The cellular and molecular mechanisms of adipose tissue biology have
      been studied extensively over the last two decades. Adipose tissue growth
      involves both an increase in fat cell size and the formation of mature adipocytes
      from precursor cells. To investigate how natural substances influence these two
      processes, we examined the effects of lotus leaf extract (Nelumbo nucifera
      extract solution obtained from Silab, France) and L-carnitine on human
      preadipocytes and adipocytes. METHODS: For our in vitro studies, we used a lotus
      leaf extract solution alone or in combination with L-carnitine. Utilizing
      cultured human preadipocytes, we investigated lotus leaf extract solution-induced
      inhibition of triglyceride incorporation during adipogenesis and possible effects
      on cell viability. Studies on human adipocytes were performed aiming to elucidate
      the efficacy of lotus leaf extract solution to stimulate lipolytic activity. To
      further characterize lotus leaf extract solution-mediated effects, we determined
      the expression of the transcription factor adipocyte determination and
      differentiation factor 1 (ADD1/SREBP-1c) on the RNA- and protein level utilizing
      qRT-PCR and immunofluorescence analysis. Additionally, the effect of L-carnitine
      on beta-oxidation was analyzed using human preadipocytes and mature adipocytes.
      Finally, we investigated additive effects of a combination of lotus leaf extract
      solution and L-carnitine on triglyceride accumulation during
      preadipocyte/adipocyte differentiation. RESULTS: Our data showed that incubation
      of preadipocytes with lotus leaf extract solution significantly decreased
      triglyceride accumulation during adipogenesis without affecting cell viability.
      Compared to controls, adipocytes incubated with lotus leaf extract solution
      exhibited a significant increase in lipolysis-activity. Moreover, cell
      populations cultivated in the presence of lotus leaf extract solution showed a
      decrease in adipocyte differentiation capacity as indicated by a decrease in the
      ADD1/SREBP-1c signal. Importantly, our results demonstrated that a combination of
      lotus leaf extract solution and L-carnitine reduced triglyceride accumulation to
      a greater extent compared to incubation with either substance alone. CONCLUSIONS:
      Overall, our data demonstrate that a combination of lotus leaf extract and L
      carnitine reduced triglyceride accumulation in human (pre)adipocytes by affecting
      different processes during the adipocyte life cycle. For this reason, this
      combination might represent a treatment option for obesity-related diseases.

PMID- 20687954
TI  - An acceptability and safety study of the Duet cervical barrier and gel delivery
      system in Zimbabwe.
AB  - BACKGROUND: Adherence problems with coitally dependent, female-initiated HIV
      prevention methods have contributed to several trials' failure to establish
      efficacy. Continuous use of a cervical barrier with once-daily cleaning and
      immediate reinsertion may simplify use for women and improve adherence. We
      assessed the acceptability and safety of precoital and continuous use of the
      Duet, a cervical barrier and gel delivery system, in Zimbabwean women. METHODS:
      Using a two-arm crossover design with a parallel observation group, we randomized
      103 women in a 2:2:1 ratio: (1) to use the Duet continuously for 14 days,
      followed by a minimum of seven days of washout and then 14 days of precoital use;
      (2) to use the same Duet regimens in reverse order; or (3) for observation only.
      Women were aged 18 to 40 years; half were recruited from a pool of previous
      diaphragm study participants and the other half from the general community.
      Acceptability and adherence were assessed through an interviewer-administered
      questionnaire at each of two follow-up visits. Safety was monitored through
      pelvic speculum exams and report of adverse events. RESULTS: The proportion of
      women who reported consistent Duet use during sex was virtually identical during
      continuous and precoital regimens (88.6% vs. 88.9%). Partner refusal was the most
      common reason cited for non-use during sex in both use regimens. Not having the
      device handy was the most common reason cited for non-daily use (in the
      continuous regimen). Most women were "very comfortable" using it continuously
      (86.3%) and inserting it precoitally (92.8%). The most favoured Duet attribute
      was that it did not interfere with "natural" sex (55%). The least favoured Duet
      attribute was the concern that it might come out during sex (71.3%). No serious
      adverse events were reported during the study; 57 participants reported 90
      adverse events classified as mild or moderate. There were no statistically
      significant differences in: (1) the proportion of women reporting adverse events;
      (2) the severity of events among those using the Duet and observational controls;
      or (3) event severity reported during each regimen use period. CONCLUSIONS: In
      this study, the Duet was found to be acceptable and safe when inserted
      precoitally or used continuously for 14 days. Assignment to use of the Duet
      continuously did not increase adherence to the Duet during sex. Future HIV
      prevention trials should evaluate use of the Duet (precoitally and continuously)
      with promising microbicide candidates.

PMID- 20687955
TI  - Nurse led, primary care based antiretroviral treatment versus hospital care: a
      controlled prospective study in Swaziland.
AB  - BACKGROUND: Antiretroviral treatment services delivered in hospital settings in
      Africa increasingly lack capacity to meet demand and are difficult to access by
      patients. We evaluate the effectiveness of nurse led primary care based
      antiretroviral treatment by comparison with usual hospital care in a typical
      rural sub Saharan African setting. METHODS: We undertook a prospective,
      controlled evaluation of planned service change in Lubombo, Swaziland. Clinically
      stable adults with a CD4 count > 100 and on antiretroviral treatment for at least
      four weeks at the district hospital were assigned to either nurse led primary
      care based antiretroviral treatment care or usual hospital care. Assignment
      depended on the location of the nearest primary care clinic. The main outcome
      measures were clinic attendance and patient experience. RESULTS: Those receiving
      primary care based treatment were less likely to miss an appointment compared
      with those continuing to receive hospital care (RR 0.37, p < 0.0001). Average
      travel cost was half that of those receiving hospital care (p = 0.001). Those
      receiving primary care based, nurse led care were more likely to be satisfied in
      the ability of staff to manage their condition (RR 1.23, p = 0.003). There was no
      significant difference in loss to follow-up or other health related outcomes in
      modified intention to treat analysis. Multilevel, multivariable regression
      identified little inter-cluster variation. CONCLUSIONS: Clinic attendance and
      patient experience are better with nurse led primary care based antiretroviral
      treatment care than with hospital care; health related outcomes appear equally
      good. This evidence supports efforts of the WHO to scale-up universal access to
      antiretroviral treatment in sub Saharan Africa.

PMID- 20687956
TI  - Health improvement and prevention study (HIPS) - evaluation of an intervention to
      prevent vascular disease in general practice.
AB  - BACKGROUND: The Health Improvement and Prevention Study (HIPS) study aims to
      evaluate the capacity of general practice to identify patients at high risk for
      developing vascular disease and to reduce their risk of vascular disease and
      diabetes through behavioural interventions delivered in general practice and by
      the local primary care organization. METHODS/DESIGN: HIPS is a stratified
      randomized controlled trial involving 30 general practices in NSW, Australia.
      Practices are randomly allocated to an 'intervention' or 'control' group. General
      practitioners (GPs) and practice nurses (PNs) are offered training in lifestyle
      counselling and motivational interviewing as well as practice visits and patient
      educational resources. Patients enrolled in the trial present for a health check
      in which the GP and PN provide brief lifestyle counselling based on the 5As model
      (ask, assess, advise, assist, and arrange) and refer high risk patients to a diet
      education and physical activity program. The program consists of two individual
      visits with a dietician or exercise physiologist and four group sessions, after
      which patients are followed up by the GP or PN. In each practice 160 eligible
      patients aged between 40 and 64 years are invited to participate in the study,
      with the expectation that 40 will be eligible and willing to participate.
      Evaluation data collection consists of (1) a practice questionnaire, (2) GP and
      PN questionnaires to assess preventive care attitudes and practices, (3) patient
      questionnaire to assess self-reported lifestyle behaviours and readiness to
      change, (4) physical assessment including weight, height, body mass index (BMI),
      waist circumference and blood pressure, (5) a fasting blood test for glucose and
      lipids, (6) a clinical record audit, and (7) qualitative data collection. All
      measures are collected at baseline and 12 months except the patient questionnaire
      which is also collected at 6 months. Study outcomes before and after the
      intervention is compared between intervention and control groups after adjusting
      for baseline differences and clustering at the level of the practice. DISCUSSION:
      This study will provide evidence of the effectiveness of a primary care
      intervention to reduce the risk of cardiovascular disease and diabetes in general
      practice patients. It will inform current policies and programs designed to
      prevent these conditions in Australian primary health care. TRIAL REGISTRATION:
      ACTRN12607000423415.

PMID- 20687957
TI  - Women's constructions of the 'right time' to consider decisions about risk
      reducing mastectomy and risk-reducing oophorectomy.
AB  - BACKGROUND: Women who are notified they carry a BRCA1/2 mutation are presented
      with surgical options to reduce their risk of breast and ovarian cancer,
      including risk-reducing mastectomy (RRM) and risk-reducing oophorectomy (RRO).
      Growing evidence suggests that a sub-group of women do not make decisions about
      RRM and RRO immediately following genetic testing, but rather, consider these
      decisions years later. Women's perspectives on the timing of these decisions are
      not well understood. Accordingly, the purpose of this research was to describe
      how women construct the 'right time' to consider decisions about RRM and RRO.
      METHODS: In-depth interviews were conducted with 22 BRCA1/2 carrier women and
      analyzed using qualitative, constant comparative methods. RESULTS: The time that
      lapsed between receipt of genetic test results and receipt of RRM or RRO ranged
      from three months to nine years. The findings highlighted the importance of
      considering decisions about RRM and RRO one at a time. The women constructed the
      'right time' to consider these decisions to be when: (1) decisions fit into their
      lives, (2) they had enough time to think about decisions, (3) they were ready
      emotionally to deal with the decisions and the consequences, (4) all the issues
      and conflicts were sorted out, (5) there were better options available, and (6)
      the health care system was ready for them. CONCLUSIONS: These findings offer
      novel insights relevant to health care professionals who provide decision support
      to women considering RRM and RRO.

PMID- 20687958
TI  - Brg-1 mediates the constitutive and fenretinide-induced expression of SPARC in
      mammary carcinoma cells via its interaction with transcription factor Sp1.
AB  - BACKGROUND: Secreted protein, acidic and rich in cysteine (SPARC) is a
      matricellular protein that mediates cell-matrix interactions. It has been shown,
      depending on the type of cancer, to possess either pro- or anti-tumorigenic
      properties. The transcriptional regulation of the SPARC gene expression has not
      been fully elucidated and the effects of anti-cancer drugs on this process have
      not been explored. RESULTS: In the present study, we demonstrated that chromatin
      remodeling factor Brg-1 is recruited to the proximal SPARC promoter region (-130/
      56) through an interaction with transcription factor Sp1. We identified Brg-1 as
      a critical regulator for the constitutive expression levels of SPARC mRNA and
      protein in mammary carcinoma cell lines and for SPARC secretion into culture
      media. Furthermore, we found that Brg-1 cooperates with Sp1 to enhance SPARC
      promoter activity. Interestingly, fenretinide [N-4(hydroxyphenyl) retinamide, 4
      HPR], a synthetic retinoid with anti-cancer properties, was found to up-regulate
      the transcription, expression and secretion of SPARC via induction of the Brg-1
      in a dose-dependent manner. Finally, our results demonstrated that fenretinide
      induced expression of SPARC contributes significantly to a decreased invasion of
      mammary carcinoma cells. CONCLUSIONS: Overall, our results reveal a novel
      cooperative role of Brg-1 and Sp1 in mediating the constitutive and fenretinide
      induced expression of SPARC, and provide new insights for the understanding of
      the anti-cancer effects of fenretinide.

PMID- 20687959
TI  - Analysis of Thisbe and Pyramus functional domains reveals evidence for cleavage
      of Drosophila FGFs.
AB  - BACKGROUND: As important regulators of developmental and adult processes in
      metazoans, Fibroblast Growth Factor (FGF) proteins are potent signaling molecules
      whose activities must be tightly regulated. FGFs are known to play diverse roles
      in many processes, including mesoderm induction, branching morphogenesis, organ
      formation, wound healing and malignant transformation; yet much more remains to
      be learned about the mechanisms of regulation used to control FGF activity.
      RESULTS: In this work, we conducted an analysis of the functional domains of two
      Drosophila proteins, Thisbe (Ths) and Pyramus (Pyr), which share homology with
      the FGF8 subfamily of ligands in vertebrates. Ths and Pyr proteins are secreted
      from Drosophila Schneider cells (S2) as smaller N-terminal fragments presumably
      as a result of intracellular proteolytic cleavage. Cleaved forms of Ths and Pyr
      can be detected in embryonic extracts as well. The FGF-domain is contained within
      the secreted ligand portion, and this domain alone is capable of functioning in
      the embryo when ectopically expressed. Through targeted ectopic expression
      experiments in which we assay the ability of full-length, truncated, and chimeric
      proteins to support cell differentiation, we find evidence that (1) the C
      terminal domain of Pyr is retained inside the cell and does not seem to be
      required for receptor activation and (2) the C-terminal domain of Ths is secreted
      and, while also not required for receptor activation, this domain does plays a
      role in limiting the activity of Ths when present. CONCLUSIONS: We propose that
      differential protein processing may account for the previously observed
      inequalities in signaling capabilities between Ths and Pyr. While the regulatory
      mechanisms are likely complex, studies such as ours conducted in a tractable
      model system may be able to provide insights into how ligand processing regulates
      growth factor activity.

PMID- 20687960
TI  - A systematic review of psychosocial interventions for family carers of palliative
      care patients.
AB  - BACKGROUND: Being a family carer to a patient nearing the end of their life is a
      challenging and confronting experience. Studies show that caregiving can have
      negative consequences on the health of family carers including fatigue, sleep
      problems, depression, anxiety and burnout. One of the goals of palliative care is
      to provide psychosocial support to patients and families facing terminal illness.
      A systematic review of interventions for family carers of cancer and palliative
      care patients conducted at the start of this millennium demonstrated that there
      was a dearth of rigorous inquiry on this topic and consequently limited knowledge
      regarding the types of interventions likely to be effective in meeting the
      complex needs of family carers. We wanted to discern whether or not the evidence
      base to support family carers has improved. Furthermore, undertaking this review
      was acknowledged as one of the priorities for the International Palliative Care
      Family Carer Research Collaboration http://www.centreforpallcare.org. METHODS: A
      systematic review was undertaken in order to identify developments in family
      carer support that have occurred over the last decade. The focus of the review
      was on interventions that targeted improvements in the psychosocial support of
      family carers of palliative care patients. Studies were graded to assess their
      quality. RESULTS: A total of fourteen studies met the inclusion criteria. The
      focus of interventions included psycho-education, psychosocial support, carer
      coping, symptom management, sleep promotion and family meetings. Five studies
      were randomised controlled trials, three of which met the criteria for the
      highest quality evidence. There were two prospective studies, five pre-test/post
      test projects and two qualitative studies. CONCLUSIONS: The systematic review
      identified a slight increase in the quality and quantity of psychosocial
      interventions conducted for family carers in the last decade. More rigorous
      intervention research is required in order to meet the supportive care needs of
      family carers of palliative care patients.

PMID- 20687961
TI  - Left hepatic trisectionectomy for hilar cholangiocarcinoma presenting with an
      aberrant biliary duct of segment 5: a case report.
AB  - INTRODUCTION: Management of the biliary ducts during liver resection is one of
      the most important challenges for hepatobiliary surgeons. Here, we report the
      case of a left hepatic trisectionectomy for hilar cholangiocarcinoma with a rare
      aberrant biliary duct of segment 5, which, to the best of our knowledge, has
      never been reported in previous literature. CASE PRESENTATION: A 56-year-old
      Asian female initially presented with intrahepatic bile duct dilatation in the
      left lateral sector, left paramedian sector, and right paramedian sector.
      Simultaneous cholangiography from a percutaneous transhepatic biliary drainage
      tube in biliary duct of segment 8 and endoscopic nasobiliary drainage tube in
      biliary duct of segment 3 revealed drainage of the right lateral sectoral branch
      into the common hepatic duct and the aberrant drainage of segment 5 into the
      right lateral sectoral branch. The left hepatic duct, right paramedian sectoral
      duct, and the confluence of the right lateral sectoral duct were narrowed. Left
      hepatic trisectionectomy was successfully performed with careful dissection and
      division of the aberrant biliary duct of segment 5. CONCLUSION: For safe liver
      resection, it is important to perform a detailed anatomic evaluation of the
      intrahepatic ducts, both preoperatively and intraoperatively.

PMID- 20687962
TI  - Embedding effective depression care: using theory for primary care organisational
      and systems change.
AB  - BACKGROUND: Depression and related disorders represent a significant part of
      general practitioners (GPs) daily work. Implementing the evidence about what
      works for depression care into routine practice presents a challenge for
      researchers and service designers. The emerging consensus is that the transfer of
      efficacious interventions into routine practice is strongly linked to how well
      the interventions are based upon theory and take into account the contextual
      factors of the setting into which they are to be transferred. We set out to
      develop a conceptual framework to guide change and the implementation of best
      practice depression care in the primary care setting. METHODS: We used a mixed
      method, observational approach to gather data about routine depression care in a
      range of primary care settings via: audit of electronic health records;
      observation of routine clinical care; and structured, facilitated whole of
      organisation meetings. Audit data were summarised using simple descriptive
      statistics. Observational data were collected using field notes. Organisational
      meetings were audio taped and transcribed. All the data sets were grouped, by
      organisation, and considered as a whole case. Normalisation Process Theory (NPT)
      was identified as an analytical theory to guide the conceptual framework
      development. RESULTS: Five privately owned primary care organisations (general
      practices) and one community health centre took part over the course of 18
      months. We successfully developed a conceptual framework for implementing an
      effective model of depression care based on the four constructs of NPT:
      coherence, which proposes that depression work requires the conceptualisation of
      boundaries of who is depressed and who is not depressed and techniques for
      dealing with diffuseness; cognitive participation, which proposes that depression
      work requires engagement with a shared set of techniques that deal with
      depression as a health problem; collective action, which proposes that agreement
      is reached about how care is organised; and reflexive monitoring, which proposes
      that depression work requires agreement about how depression work will be
      monitored at the patient and practice level. We describe how these constructs can
      be used to guide the design and implementation of effective depression care in a
      way that can take account of contextual differences. CONCLUSIONS: Ideas about
      what is required for an effective model and system of depression care in primary
      care need to be accompanied by theoretically informed frameworks that consider
      how these can be implemented. The conceptual framework we have presented can be
      used to guide organisational and system change to develop common language around
      each construct between policy makers, service users, professionals, and
      researchers. This shared understanding across groups is fundamental to the
      effective implementation of change in primary care for depression.

PMID- 20687963
TI  - "I know I have arthritis but I don't know what type". Understanding and knowledge
      of this chronic condition.
AB  - BACKGROUND: "Arthritis" is a common musculoskeletal condition but the knowledge
      of what type of arthritis people have, may be limited but may have changed over
      time in response to campaigns, increased awareness and improved health literacy.
      This paper describes people who did not know what type of arthritis they had, by
      a range of relevant demographic and socioeconomic variables, and assesses changes
      over time in the proportion of people who report having arthritis but do not know
      what type, using representative population surveillance data. METHODS: Data were
      collected using the South Australian Monitoring and Surveillance System (SAMSS),
      a risk factor surveillance system where each month, a representative random
      sample of South Australians is selected from the Electronic White Pages, with
      interviews conducted using computer assisted telephone interviewing (CATI). Data
      were used for the period January 2006 to December 2008 (n = 16465) for
      respondents aged 18 years and over. RESULTS: Overall, the proportion of
      respondents who did not know what type of arthritis they had, among people aged
      18 years and over, for 2006 to 2008 was 6.5% (95% CI 6.1-6.9). When considering
      only those respondents reporting that they had been told by a doctor that they
      had arthritis, 30.1% did not know what type of arthritis they had. Multivariate
      analysis indicated that males, those with have a trade, certificate or diploma or
      secondary level of education, who spoke a language other than English at home,
      were widowed and earned $20,001 to $60,000, more than $80,000 or did not state
      their income were more likely to maintain that they did not know what type of
      arthritis they had. CONCLUSIONS: Population ageing and an increase in arthritis
      prevalence in the future will further increase the burden of arthritis. These
      increases in prevalence are not inevitable, especially if investments are made in
      public health prevention programs, particularly those addressing cultural and
      linguistic diversity and differences in socio-economic status and health
      literacy.

PMID- 20687964
TI  - High throughput generation of promoter reporter (GFP) transgenic lines of low
      expressing genes in Arabidopsis and analysis of their expression patterns.
AB  - BACKGROUND: Although the complete genome sequence and annotation of Arabidopsis
      were released at the end of year 2000, it is still a great challenge to
      understand the function of each gene in the Arabidopsis genome. One way to
      understand the function of genes on a genome-wide scale is expression profiling
      by microarrays. However, the expression level of many genes in Arabidopsis genome
      cannot be detected by microarray experiments. In addition, there are many more
      novel genes that have been discovered by experiments or predicted by new gene
      prediction programs. Another way to understand the function of individual genes
      is to investigate their in vivo expression patterns by reporter constructs in
      transgenic plants which can provide basic information on the patterns of gene
      expression. RESULTS: A high throughput pipeline was developed to generate
      promoter-reporter (GFP) transgenic lines for Arabidopsis genes expressed at very
      low levels and to examine their expression patterns in vivo. The promoter region
      from a total of 627 non- or low-expressed genes in Arabidopsis based on
      Arabidopsis annotation release 5 were amplified and cloned into a Gateway vector.
      A total of 353 promoter-reporter (GFP) constructs were successfully transferred
      into Agrobacterium (GV3101) by triparental mating and subsequently used for
      Arabidopsis transformation. Kanamycin-resistant transgenic lines were obtained
      from 266 constructs and among them positive GFP expression was detected from 150
      constructs. Of these 150 constructs, multiple transgenic lines exhibiting
      consistent expression patterns were obtained for 112 constructs. A total 81
      different regions of expression were discovered during our screening of positive
      transgenic plants and assigned Plant Ontology (PO) codes. CONCLUSIONS: Many of
      the genes tested for which expression data were lacking previously are indeed
      expressed in Arabidopsis during the developmental stages screened. More
      importantly, our study provides plant researchers with another resource of gene
      expression information in Arabidopsis. The results of this study are captured in
      a MySQL database and can be searched at
      http://www.jcvi.org/arabidopsis/qpcr/index.shtml. Transgenic seeds and constructs
      are also available for the research community.

PMID- 20687965
TI  - MiR-145, a new regulator of the DNA fragmentation factor-45 (DFF45)-mediated
      apoptotic network.
AB  - BACKGROUND: MicroRNA-145 (miR-145) is considered to play key roles in many
      cellular processes, such as proliferation, differentiation and apoptosis, by
      inhibiting target gene expression. DNA Fragmentation Factor-45 (DFF45) has been
      found to be the substrate of Caspase-3, and the cleavage of DFF45 by caspase-3
      during apoptosis releases DFF40 that degrades chromosomal DNA into nucleosomal
      fragments. There are currently no in-depth studies on the relationship between
      miR-145 and the DFF45 gene. RESULTS: In this study, we identified DFF45 as a
      novel target of miR-145. We demonstrated that miR-145 targets a putative binding
      site in the coding sequence (CDS) of DFF45, and its abundance is inversely
      associated with DFF45 expression in colon cancer cells. Using a luciferase
      reporter system, we found that miR-145 suppresses the expression of the
      luciferase reporter gene fused to the putative binding site of DFF45. The level
      of DFF45 protein, but not DFF45 mRNA, was decreased by miR-145, suggesting a
      mechanism of translational regulation. Furthermore, we demonstrate that this
      specific silencing of DFF45 by miR-145 accounts, at least in part, for the
      staurosporine-induced tumor cell apoptosis in vitro. CONCLUSIONS: Our study
      reveals a previously unrecognized function of miR-145 in DFF45 processing, which
      may underlie crucial aspects of cancer biology.

PMID- 20687966
TI  - Risk factors and obstetric complications of large for gestational age births with
      adjustments for community effects: results from a new cohort study.
AB  - BACKGROUND: High birth weight has serious adverse impacts on chronic health
      conditions and development in children. This study identifies the social
      determinants and obstetric complications of high birth weight adjusted for
      gestational age and baby gender. METHODS: Pregnant women were recruited from
      three maternity hospitals in South-East Queensland in Australia during antenatal
      clinic visits. A questionnaire was completed by each participant to elicit
      information on eco-epidemiological exposures. Perinatal information was extracted
      from hospital birth records. A hierarchical mixture regression model was used in
      the analysis to account for the heterogeneity of birth weights and identify risk
      factors and obstetric complications of births that were large for gestational
      age. A generalized linear mixed model was used to adjust for (random) "community"
      effects. RESULTS: Pre-pregnancy obesity (adjusted OR = 2.73, 95% CI = 1.49-5.01),
      previous pregnancy (adjusted OR = 2.03, 95% CI = 1.08-3.81), and married mothers
      (adjusted OR = 1.85, 95% CI = 1.00-3.42) were significantly associated with large
      for gestational age babies. Subsequent complications included the increased need
      for delivery by caesarean sections or instrumental procedures (adjusted OR =
      1.98, 95% CI = 1.10-3.55), resuscitation (adjusted OR = 2.52, 95% CI = 1.33
      4.79), and transfer to intensive/special care nursery (adjusted OR = 3.76, 95% CI
      = 1.89-7.49). Communities associated with a higher proportion of large for
      gestational age births were identified. CONCLUSIONS: Pre pregnancy obesity is the
      principal modifiable risk factor for large for gestational age births. Large for
      gestational age is an important risk factor for the subsequent obstetric
      complications. The findings improve the evidence-base on which to base preventive
      interventions to reduce the impact of high birth weight on maternal and child
      health.

PMID- 20687967
TI  - The effect of external beam radiotherapy volume on locoregional control in
      patients with locoregionally advanced or recurrent nonanaplastic thyroid cancer.
AB  - PURPOSE: We evaluated outcomes of patients treated with external beam
      radiotherapy (EBRT) for locoregionally advanced or recurrent nonanaplastic
      thyroid cancer and analyzed the effect of EBRT volume on locoregional control.
      METHODS: This study included 23 patients with locoregionally advanced or
      recurrent nonanaplastic thyroid cancer who were treated with EBRT. Two different
      EBRT target volumes were executed as follows: 1) limited field (LF, n = 11)
      included the primary (involved lobe) or recurrent tumor bed and the positive
      nodal area; 2) elective field (EF, n = 12) included the primary (involved lobe)
      or recurrent tumor bed and the regional nodal areas in the cervical neck and
      upper mediastinum. Clinical parameters, such as gender, age, histologic type,
      recurrence, stage, thyroglobulin level, postoperative residuum, radioiodine
      treatment, and EBRT volume were analyzed to identify prognostic factors
      associated with locoregional control. RESULTS: There were no significant
      differences in the clinical parameter distributions between the LF and EF groups.
      In the LF group, six (55%) patients developed locoregional recurrence and three
      (27%) developed distant metastasis. In the EF group, one (8%) patient developed
      locoregional recurrence and one (8%) developed a distant metastasis. There was a
      significant difference in locoregional control rate at 5 years in the LF and EF
      groups (40% vs. 89%, p = 0.041). There were no significant differences in
      incidences of acute and late toxicities between two groups (p >0.05).
      CONCLUSIONS: EBRT with EF provided significantly better locoregional control than
      that of LF; however, further larger scaled studies are warranted.

PMID- 20687968
TI  - Genotoxic and carcinogenic risks associated with the dietary consumption of
      repeatedly heated coconut oil.
AB  - Repeated heating of vegetable oils at high temperatures during cooking is a very
      common cooking practice. Repeated heating of edible oils can generate a number of
      compounds, including polycyclic aromatic hydrocarbons (PAH), some of which have
      been reported to have carcinogenic potential. Consumption of these repeatedly
      heated oils can pose a serious health hazard. The objectives of the present study
      were to evaluate the genotoxic and carcinogenic risks associated with the
      consumption of repeatedly heated coconut oil (RCO), which is one of the commonly
      consumed cooking and frying medium. The PAH were analysed using HPLC in fresh CO,
      single-heated CO (SCO) and RCO. Results revealed the presence of certain PAH,
      known to possess carcinogenic potential, in RCO when compared with SCO. Oral
      intake of RCO in Wistar rats resulted in a significant induction of aberrant
      cells (P<0.05) and micronuclei (P<0.05) in a dose-dependent manner. Oxidative
      stress analysis showed a significant (P<0.05) decrease in the levels of
      antioxidant enzymes such as superoxide dismutase and catalase with a concurrent
      increase in reactive oxygen species and lipid peroxidation in the liver. In
      addition, RCO given alone and along with diethylnitrosamine for 12 weeks induced
      altered hepatic foci as noticed by alteration in positive (gamma-glutamyl
      transpeptidase and glutathione-S-transferase) and negative (adenosine
      triphosphatase, alkaline phosphatase and glucose-6-phosphatase) hepatospecific
      biomarkers. A significant decrease in the relative and absolute hepatic weight of
      RCO-supplemented rats was recorded (P<0.05). In conclusion, dietary consumption
      of RCO can cause a genotoxic and preneoplastic change in the liver.

PMID- 20687969
TI  - The inhibitory effect of genistein on hepatic steatosis is linked to visceral
      adipocyte metabolism in mice with diet-induced non-alcoholic fatty liver disease.
AB  - Non-alcoholic fatty liver disease (NAFLD) has been deeply associated with
      visceral adiposity, adipose tissue inflammation and a variety of adipocytokines.
      We reported previously that genistein inhibited NAFLD by enhancing fatty acid
      catabolism. However, this molecular approach focused on hepatic metabolism. Thus,
      we have attempted to determine whether this anti-steatotic effect of genistein is
      linked to visceral adipocyte metabolism. C57BL/6J mice were fed on normal-fat
      (NF) diet, high-fat (HF) diet and HF diet supplemented with genistein (1, 2 and 4
      g/kg diet) for 12 weeks. Mice fed on the HF diet gained body weight, exhibited
      increased visceral fat mass and elevated levels of serum and liver lipids, and
      developed NAFLD, unlike what was observed in mice fed on the NF diet. However,
      genistein supplementation (2 and 4 g/kg diet) normalised these alternations. In
      the linear regression analysis, visceral fat (R 0.77) and TNFalpha (R 0.62) were
      strongly correlated with NAFLD among other NAFLD-related parameters. Genistein
      supplementation suppressed the hypertrophy of adipocytes via the up-regulation of
      genes involved in fatty acid beta-oxidation, including PPARalpha, 5'-AMP
      activated protein kinase and very long-chain acyl CoA dehydrogenase, as well as
      through the down-regulation of genes associated with adipogenesis or lipogenesis,
      including liver X receptor-alpha, sterol-regulatory element-binding protein-1c,
      PPARgamma, retinoid X receptor-alpha and acetyl CoA carboxylase 2. Moreover,
      genistein supplementation augmented an anti-steatohepatitic adiponectin TNF and
      reduced a steatohepatitic TNFalpha. Collectively, these findings show that
      genistein may prevent NAFLD via the regulation of visceral adipocyte metabolism
      and adipocytokines.

PMID- 20687970
TI  - Effect of multifibre mixture with prebiotic components on bifidobacteria and
      stool pH in tube-fed children.
AB  - The objective of the present study was to evaluate the effect of a paediatric
      tube feed supplemented with a multifibre mixture on the gut microbiota and
      nutritional and micronutrient status of children on long-term enteral nutrition
      (EN). A randomised, controlled, double-blind, cross-over trial (2 * 3 months)
      with a washout period of 1 month was carried out. Twenty-seven children (80%
      neurologically impaired) aged 11.9 (SD 3.9) years, on long-term EN (4.8 (SD 3.9)
      years) were recruited. The analyses of the children's faecal pH, microbiota along
      with anthropometric measures, bowel movements and markers of blood micronutrient
      status were made. Twenty children completed the study. A significant increase in
      the proportion of stool bifidobacteria (+16.6%, P < 0.05) was observed during the
      multifibre period than during the fibre-free period, together with a significant
      reduction in stool pH (P < 0.001). Stool frequency and consistency as well as
      growth did not differ between the two periods. There was a significant increase
      (P < 0.05) in plasma ferritin at the end of the fibre-free period, but plasma
      ferritin levels remained within normal ranges during both periods. No diet
      effects on other blood parameters were observed. In conclusion, addition of a
      multifibre mixture with prebiotic components to paediatric EN is well tolerated,
      promotes bifidobacteria and reduces stool pH, indicating an improved gut health.

PMID- 20687971
TI  - Effect of dietary fibre mixture on growth and intestinal iron absorption in rats
      recovering from iron-deficiency anaemia.
AB  - There is concern regarding the possible negative effects of ingestion of dietary
      fibre on growth and intestinal Fe absorption in infants. The aim of the present
      study was to compare the effect of a fibre mixture on the growth and the
      intestinal absorption of Fe in rats with Fe-deficiency anaemia with that of a
      diet without fibres. Faecal weight and caecal pH were also evaluated. According
      to the Hb depletion-repletion model, twenty-two male weaned Wistar rats were fed
      the AIN93-G diet without Fe until Fe-deficiency anaemia was induced with Hb < 70
      g/l. The anaemic rats were divided into two groups: (1) fibre mixture group--fed
      100 g of fibre mixture/kg of diet (soya polysaccharide, inulin, resistant starch,
      Arabic gum, fructo-oligossaccharide and cellulose) (n 11); (2) control group--fed
      without fibres (n 11). All diets had 157 mg of ferric citrate (30 mg of elemental
      Fe) added to lead to recovery from anaemia. Fe intestinal absorption was measured
      by Hb repletion efficiency (HRE) and apparent Fe intestinal absorption. The HRE
      was 44.8 (SD 9.5) % in the fibre mixture group and 43.0 (SD 9.5) % in the control
      group (P = 0.664). The apparent Fe absorption was 46.2 (SD 16.5) and 47.2 (SD
      10.2) % (P = 0.861) in the fibre mixture and control groups, respectively. The
      faecal weight median was 6.17 g in the fibre mixture group and 2.11 g in the
      control group (P < 0.001). The caecal pH was in the same order: 6.11 (SD 0.59)
      and 7.07 (SD 0.34) (P < 0.001). Both the groups consumed similar quantities of
      diet, and growth was similar in both the groups. The fibre mixture had no
      influence either on growth or on Fe intestinal absorption in rats recovering from
      anaemia. This mixture favoured an increase in faecal weight and a decrease in
      caecal pH.

PMID- 20687972
TI  - The private cost of long-term care in Canada: where you live matters.
AB  - Canadians expect the same access to health care whether they are rich or poor,
      and wherever they live, often without direct charge at the point of service.
      However, we find that the private cost of long-term care differs greatly across
      the country, and within provinces, we find substantial variation, depending on
      income level, marital status, and, in Quebec alone, on assets owned. A non
      married person with average income would pay more than twice as much in the
      Atlantic provinces as in Quebec, while a couple with one in care would pay almost
      four times as much in Newfoundland as in Alberta.

PMID- 20687973
TI  - 'It is nice to see someone coming in': exploring the social objectives of Meals
      on-Wheels.
AB  - Despite the fact that Meals-on-Wheels have both nutritional and social aspects,
      research on the social objectives of the service is lacking. This study set out
      to develop an understanding of the social objectives of Meals-on-Wheels and to
      explore the extent to which they are met by Ireland's Meals-on-Wheels services. A
      literature review suggested that Meals-on-Wheels services can potentially meet
      three social objectives: (a) providing meals recipients with social contact, (b)
      helping to restimulate an interest in meals and regularising mealtimes, and (c)
      helping to develop acceptance of the service. Interviews were conducted with 66
      meals recipients to explore these themes and augment them as necessary. Study
      results show that meals recipients derive limited social contact from the
      service; regularising mealtimes was not important to most recipients; and many
      were reluctant to accept the service. The three objectives are therefore
      minimally met within the Irish system at present.

PMID- 20687974
TI  - Life around ... : staff's perceptions of residents' adjustment into long-term
      care.
AB  - The move to a long-term care facility can be particularly traumatic for new
      residents. Staff can make this transition easier in a number of ways. However,
      the staff's perceptions of the transition process and residents' experiences will
      play a significant part in determining the type of support that is given
      residents during the transition. The purpose of this research was to examine the
      staff's perceptions of a person's coming to live in a long-term care environment.
      Using in-depth interviews with staff from one long-term care facility, three main
      themes emerged that encompassed descriptions of residents' lives. Essentially,
      the staff described how residents learned to live a life involving various
      factors in three main categories--life around losses, life around the
      institution, and life around the body.

PMID- 20687983
TI  - [Scientific production in international journals by Acta Medica Portuguesa
      authors].
AB  - Local and national scientific journals have been widely criticized by some
      authors. Additionally, they are quite rarely indexed at international databases,
      which results in a reduced visibility of their articles. OBJECTIVE: To analyze
      international scientific productions of authors publishing in Acta Medica
      Portuguesa during 2008. METHODS: A database with all the authors publishing in
      Acta Medica Portuguesa in 2008 was built. In July 2009, production of all those
      authors from the previous five years (2003-2007) was retrieved from Science
      Citation Index. Journals where they published, Impact Factors of those journals,
      articles' references, and times cited were analyzed. RESULTS: The 78 articles
      published by Acta Medica Portuguesa in 2008 were produced by 259 different
      authors. Ninety four (36.3%) of those authors wrote 420 articles from 2003 to
      2007 indexed at Science Citation Index. These articles were published in 249
      different journals, with an average Impact Factor of 2.973 (SD = 2.92). Journal
      with highest Impact Factor was The Lancet (IF2008 = 28.409) with two papers
      published. Eighty seven of those authors received some citation to their
      articles, with a total amount of 5001 cites. Out of the 14035 references on those
      420 articles, only 10 cited any article published in Acta Medica Portuguesa.
      CONCLUSION: Authors publishing in Acta Medica Portuguesa produce a good amount of
      international publications in journals with an acceptable Impact Factor and they
      receive quite a good number of citations. Conversely, these authors when
      publishing in international journals have an extremely low citation of articles
      published in Acta Medica Portuguesa.

PMID- 20687984
TI  - [Sugary drinks and glycemia].
AB  - Obesity prevalence is increasing all over the world. Most affected are people
      changing from a traditional lifestyle to an environment with both availability of
      high energy diet and less physical activity. Glycemic index (GI) is a measure of
      dietary glycemic carbohydrates, representing their ability to raise blood glucose
      concentrations. It refers to the postprandial blood glucose response expressed as
      a percentage of the response to a reference food (glucose or white bread)
      containing the same carbohydrate content. Given the present high consumption of
      sugary drinks, the putative contribution of these products to obesity deserves
      investigation. The aim of this study was to determine the GI of some drinks from
      the Portuguese market. Postprandial glycemia after ingestion of apple Frutis,
      peach Frutis, Green tea Frutea, green tea, black tea, lupin infusion, rooibos
      infusion, raftilose solution or bran solution has been determined for two hours
      in a caucasian population of young adults of any sex, 17 to 24 years of age.
      Apple Frutis GI was found to be 54.3, i.e., a low GI; Frutea Green tea had a GI
      of 64.7, considered as a moderate GI; peach Frutis showed a high GI, 86.6. Green
      and Black teas as well as rooibos and lupin infusions, all with added glucose (25
      g), did not change glycemic response in comparison with the reference solution
      (water with 25 g glucose). No differences were seen after raftilose and bran
      solutions by comparison with the reference solution. GI information may help the
      choice of carbohydrates to include in a healthy diet. Formerly considered as a
      parameter of interest to diabetic patients, it may actually interest anybody
      concerned with a healthy diet. This study has been performed by medical and
      nutritional science students, who observed glycemic excursions in themselves,
      after drink ingestion. This experiment allowed them to see the impressive rise of
      glycemia after ingestion of a sugary drink, by comparison with basal levels which
      would not rise if plain water or other nonsugary drink had been ingested.

PMID- 20687982
TI  - Twelve-week efficacy and safety study of mometasone furoate/formoterol 200/10
      microg and 400/10 microg combination treatments in patients with persistent
      asthma previously receiving high-dose inhaled corticosteroids.
AB  - A significant unmet medical need exists in patients with uncontrolled asthma. The
      purpose of this study was to evaluate the efficacy and safety of mometasone
      furoate/formoterol (MF/F) 400/10 microg versus MF 400 microg administered twice
      daily (b.i.d.) via metered-dose inhaler in patients with asthma uncontrolled on
      high-dose inhaled corticosteroids (ICS). In a 12-week, randomized, multicenter,
      double-blind, parallel-group study, patients (>or=12 years of age) were
      randomized to MF/F 200/10 microg, MF/F 400/10 microg, or MF 400 microg, b.i.d.
      after a 2- to 3-week open-label run in with MF 400 microg b.i.d. The primary end
      point was mean change in area under the curve from 0 to 12 hours in forced
      expiratory volume in 1 second (FEV(1) AUC(0-12h)) from baseline to week 12 for
      MF/F 400/10 microg versus MF 400 microg. Effects of MF/F on asthma control and
      symptoms were evaluated and adverse events recorded. Seven hundred twenty-eight
      patients were randomized. Significant improvement from baseline to week 12
      occurred for mean change in FEV(1) AUC(0-12h) with MF/F 400/10 microg (4.19 L x
      hour) versus MF 400 microg (2.04 L x hour; p < 0.001). Both MF/F doses resulted
      in rapid (5 minutes) and sustained improvement in lung function throughout 12
      weeks. Both MF/F doses were superior to MF in improving asthma control and
      reducing nocturnal awakenings due to asthma requiring short-acting beta(2)
      agonist use. All treatments were well tolerated. Asthma patients who were poorly
      controlled on high-dose ICS experienced significant improvement in asthma
      control, lung function, and symptoms when treated with MF/F compared with MF.

PMID- 20687985
TI  - [Association of gamma glutamyltransferase, metabolic syndrome and cardiovascular
      risk].
AB  - Serum gamma-glutamyl transferase (GGT) has been used as a marker of alcohol
      induced liver disease. Recent epidemiology and pathology studies have suggested
      its independent role in the pathogenesis and clinical evolution of cardiovascular
      diseases (CVD) promoting atherosclerosis through an oxidative process leading,
      within the atherosclerotic plaque, to LDL oxidation, metalloproteinase
      activation, cell proliferation and apoptosis. Besides it is known that GGT levels
      rise even in the normal range, with obesity and hepatic steatosis occurs, it is
      thought, which originates insulin resistance (IR). Being sure that IR is
      important in the development of type 2 diabetes and CVD, both very prevalent in
      Portugal, the authors considered as relevant to study the association of GGT with
      markers of multiple metabolic derangements: insulin-resistance (hyperinsulinemia,
      hyperglicemia, IR-HOMA = 3), obesity and dyslipidemia. So, a Portuguese sample
      population, consisted of 123 subjects (52 male and 71 female) was organized. As
      results were observed: elevation of GGT serum levels with the increasing risk of
      every marker and the same happened with metabolic syndrome and its components;
      compared with non obese the group of obese subjects exhibited elevated prevalence
      of risk factors, though in non obese subjects the percentages of insulin
      resistance and dyslipidemias were high (hypercholesterolemia in both sexes,
      hypertriglyceridemia and low concentrations of HDL-c in men); association of
      serum GGT levels with every risk factor and metabolic syndrome. Though, as the
      association with the insulin-resistance state was particularly strong, it is
      thought that a high prevalence of non-alcoholic fatty liver disease (NAFLD) was
      present in the studied population. As serum determination of GGT activity is a
      low-cost, highly sensitive, accurate and frequently used laboratory test and
      there is association of this enzyme with the most important risk factors of
      diabetes type 2 and CVD, its serum levels should be considered as a marker of
      insulin-resistance when NAFLD is supposed to be present or there is obesity.

PMID- 20687986
TI  - [Transobturator tapes for stress urinary incontinence treatment: middle-term
      results].
AB  - INTRODUCTION: Minimal invasive surgical treatment of female stress urinary
      incontinence with suburethral transobturator tapes is completely accepted
      nowadays. The purpose of this study is to evaluate the efficacy and security of
      these suburethral tapes, comparing the outside-in to the inside-out approach.
      MATERIAL AND METHODS: We performed a retrospective study of 298 patients with
      stress urinary incontinence diagnosis that were submitted to transobturator
      surgery between 2003 and 2006. From these patients 113 women underwent outside-in
      approach and 185 patients had inside-out approach. RESULTS: The mean-age of the
      patients was 57.2 +/- 10.3 years-old and 69.1% were in the post-menopausal
      period. Mean parity was 2.2 +/- 1.1. The outside-in approach was performed more
      frequently in association with other(s) pelvic floor surgery(ies) (83.2% versus
      37.8% for the inside-out technique). The mean follow-up duration was of 14.35 +/-
      13.75 months in those patients who had a transobturator outside-in technique and
      of 11.79 +/- 10.39 months in the inside-out group. In respect to the efficacy,
      results were identical in the two groups with cure and cure or improvement rates
      respectively of 76.9% and 92.9% in the outside-in group and of 82.7% and 93.5% in
      the inside-out group (differences not significative). Regarding mean procedure
      duration, when it was performed isolated, we had a significant lower duration in
      patients submitted to inside-out technique (14.77 +/- 5.37 minutes versus 21.21
      +/- 7.48 minutes, p < 0.05). The post-operative rates of de novo urge
      incontinence and mesh erosions were identical in the two groups, however
      microporous tapes had more erosions than macroporous ones (p < 0.05). DISCUSSION
      AND CONCLUSIONS: The transobturator suburethral tapes are effective and safe for
      the stress urinary incontinence treatment. We had elevated cure and improvement
      rates with no significant differences in regard to performed procedure. The
      inside-out technique is significantly associated to a lower operative duration.

PMID- 20687988
TI  - [Pertussis hospitalisations: Northern Region of Portugal, 2000-2006].
AB  - Pertussis is an acute bacterial disease involving the respiratory tract. The
      causal agent is Bordetella pertussis. Among all age groups, infants (aged < 12
      months) have had the highest incidence of pertussis in the vaccine era. The
      majority of hospitalisations, complications and deaths occurred in that age
      group. The aim of this study was to describe and characterize the epidemiological
      pattern of hospitalized pertussis cases during the period of 2000-2006 in the
      hospitals of Northern Portugal. We conducted a retrospective observational study
      based on hospitalisations in the Northern region of Portugal between 2000 and
      2006. Descriptive summary statistics for all variables were calculated at region,
      district and municipality levels. The average rates of hospitalisation were
      calculated per 100,000 population for the region, district and municipality,
      according to sex and age group. The severity of disease was evaluated on the
      basis of the average length of hospitalisation, the proportion of patients
      treated in intensive care units, and the case fatality rate. Three hundred and
      twenty two cases were identified between 2000 and 2006 in the Northern region of
      Portugal. Viana do Castelo and Braga districts were those who had the highest
      hospitalisations rate. In the district of Braganca there were no cases of
      hospitalisation with the diagnosis of pertussis. Fifty six per cent of the cases
      were male. The proportion of infants hospitalized under one year was 91.0 %.
      Cases among infants younger than two months accounted for 43.5 % of all cases.
      The mean annual hospitalisation incidence rate for infants under one year was 114
      per 100,000. The mean length of hospital stay was eight days. The proportion of
      patients treated in intensive care units was 11.0 %, and case fatality rate was
      0.3 %. This hospital-based study indicates that pertussis continues to be an
      important cause of morbidity and mortality in infants. Pertussis incidence
      remains high among infants, most of whom are under one year of age. Immunization
      strategies in the adult population must be reviewed and updated in order to
      attain higher protection of the more vulnerable paediatric population.

PMID- 20687987
TI  - [Hemogram reference values for Lisbon metropolitan area population].
AB  - The haemogram is, probably, one of the most requested analysis for laboratorial
      evaluation not only for ill patients but also in periodic evaluation of healthy
      subjects, allowing us to foil the presence of eventual illness, since there is an
      enormous variety of pathologies that can induce haemogram changes. The
      haematological parameters of healthy subjects are influenced by numerous factors.
      The ideal would be each laboratory should determine and establish his own
      reference values for each parameter, having in account all the variables. Since
      the available data for haematological parameters in the Portuguese population is
      very insufficient, it becomes necessary to report to exterior data based in
      populations with different characteristics from ours, which makes reference
      values' reliability questionable. To overcome this problem, we felt the necessity
      to evaluate our own population (healthy adults from metropolitan Lisbon area)
      concerning haemogram reference values, comparing the obtained results with those
      from the bibliography. We analyzed 363 blood samples from blood-donors that
      fulfilled the previously established protocol. The samples were collected before
      blood donation and the haemograms were done on the same day. We proceeded to the
      informatic registration of haemogram results, to the gathering of important data,
      to the characterization of the target population and to the statistical analysis
      of the obtained results. The sample population was globally analyzed and several
      groups were compared, according to sex, age group and possible history of smoking
      habits. Although we did not find in the bibliography data concerning the
      quantitative analysis of similar groups compared to ours, globally we concluded
      that the obtained results are similar to those described by other authors, both
      in qualitative and quantitative terms. The obtained results can only be of
      reference for this population and created subgroups. The definition of reference
      values for the Portuguese population requires the study of a much larger sample,
      due to the populational diversity that characterizes our country.

PMID- 20687989
TI  - [Healthcare associated infection: emerging problem in a neurology department].
AB  - BACKGROUND: Healthcare-associated infection (HAI) is, nowadays, a serious
      problem, contributing a lot to the burden of the hospital stays. Its impact is
      really huge and the study of these matters is taking a growing interest. AIMS: To
      compare, in terms of HAI, the current Neurology Department (localized inside the
      building of Hospital Geral) and the oldest one, which was far away from the
      institutional campus. To identify difficulties regarding the management of HAI,
      trying to propose measures for quality improvement. METHODS: We revised the
      clinical files of the patients with HAI documented by culture, on a homologue
      period of 6 months. Variables like more frequently isolated microorganisms,
      antibiotics sensibilities, patients' comorbidities, treatment adequacy and
      duration of hospitalization were analyzed. RESULTS: In the oldest Department, 23
      patients were identified, 8 men (mean +/- 2SD: 80.4 +/- 9.04 years old) and 15
      women (77.3 +/- 21.28 years old), with positive microbiological studies (51).
      Ischemic stroke caused 73.9% of these hospitalizations. Escherichia coli - EC -
      (27%), methicillin-resistant Staphylococcus aureus - MRSA - (22%) and Klebsiella
      pneumoniae - KP - (10%) were the most frequently identified microorganisms in the
      biological samples studied (sputum, urine, blood, urethral exudate and eschar).
      Amoxicillin/clavulanic acid was the most empirically used antibiotic (only
      effective on 37% of the cases, according to the sensibility tests).
      Hospitalizations had an average of 22 days and 1.3 antibiotics per patient were
      used. At discharge, Rankin had a mode of 5. In the current Department, 46
      patients were studied, 22 men (76.4 +/- 22.6 years old) and 24 women (74.1 +/-
      32.6 years old), having 119 positive cultures. Again, ischemic stroke caused the
      majority of the admissions (52.2%). MRSA (26%), Pseudomonas aeruginosa - PA -
      (17%) and EC (17%) were the most prevalent pathogens (the same biological
      products were studied, plus lingual exudates and central venous catheter tips).
      Ciprofloxacin was the most used antibiotic (suitable on 75% of the cases).
      Internments had an average of 24.3 days and, this time, 2.5 antibiotics were used
      per patient, by mean. At discharge, Rankin evaluation had again a mode of 5.
      DISCUSSION: Despite the taken measures and change in facilities, HAI had really
      increased in the Neurology Department. Since human resources are the same, we
      think are important, as possible aggravating conditions, space restriction and
      ward sharing with patients of other medical specialities, as it happens in the
      current Department. CONCLUSIONS: More aggressive pathogens require a rapid and
      comprehensive intervention, in order to minimize its impact on daily clinical
      practice and in the management of hospital stays.

PMID- 20687990
TI  - [Clinical predictors of infectious pulmonary tuberculosis.].
AB  - INTRODUCTION: The immediate identification of infectious tuberculosis and
      implementation of effective isolation measures, are a priority of the national
      policies for disease control. OBJECTIVES: To identify clinical predictor's
      factors related with sputum smear-positive, in patients with pulmonary
      tuberculosis diagnosis. POPULATION AND METHODS: This was a retrospective study
      involving 289 patients admitted consecutively with the diagnosis of tuberculosis
      (ICD-9-CM: 010-018) through the emergency department of a Central Hospital. The
      study was conducted from January 1999 to December 2005. RESULTS: 216 patients
      (74.7%) were identified with pulmonary tuberculosis: mean age 40.3 (SD 16.1);
      77.8% males. Of these 179 (82%) were smear-positive and 157 (54.5%) had human
      immunodeficiency virus (HIV) co-infection. Of the 37 patients with sputum
      smearnegative 18 (48.6%) had culture positive. The clinical factors that were
      better related with sputum smear-positive were: cough with sputum (p = 0.031) and
      classic chest radiograph patterns, parenchymal consolidation (p < 0.001) and
      cavitation (p = 0.002). HIV co-infection wasn't associated with a higher risk of
      infectious tuberculosis. CONCLUSIONS: Respiratory symptoms and classic patterns
      on chest radiograph, were clinical factors better related with a higher
      probability of sputum smear-positive. In these patients it is a good clinical
      practice to propose immediate isolation measures even before the results of
      sputum smear.

PMID- 20687991
TI  - [Multiple sclerosis: social and economic implications].
AB  - Multiple Sclerosis (MS) is the most common demyelinating disease of the Central
      Nervous System. It is more frequently diagnosed in young individuals between 20
      and 40 years old. MS is the leading non-traumatic cause for disability in young
      adults in western countries. Portuguese prevalence of the disease is about 50 per
      100,000 inhabitants, which means that there are around 5,000 people with MS in
      Portugal. Our goal was to determine social and economic implications of MS
      through the description of patient's quality of life and economic difficulties,
      and to assess the dividend spent by the National Health System (NHS) with this
      disease. The studied population consisted of 50 individuals with MS in any stage
      of the disease to whom no exclusion criteria were used. The following
      questionnaires were applied: Multiple Sclerosis: Socio-Economic Implications and
      MS and Quality of Life (MSQoL-54). For data processing purposes we used SPSS v.16
      and Microsoft Excel 2003. The confidence interval was 95%. In addition we based
      the cost calculations on K and C constants (official values from 2002). The
      results obtained were similar to those described in literature in what concerns
      the clinical presentation and the onset of the disease. Social implications
      evaluated by MSQoL revealed the majority of the inquiries had a score above 50 (n
      = 31). In what concerns economic implications the value of 40 843 250 euro was
      obtained as the minimum spent by NHS. This number probably represents an under
      valorization of the real value since only the direct costs were analyzed. It is
      necessary that new studies especially with bigger study populations can determine
      precisely the economic impact of MS in the Portuguese society.

PMID- 20687992
TI  - [Evaluation of the antimicrobial susceptibility profile of microorganisms
      isolated from urine in the region of Vale do Sousa and Tamega].
AB  - The urinary tract is one of the more common sites of bacterial infections,
      especially in women. Urinary infection can be defined as an infection of urinary
      tract structures which occurs, generally, as a consequence of the presence or
      colonization by urine bacteria. The aim of this study was to determine the
      etiology of urinary tract infections and their susceptibility to antimicrobial
      agents in the region of Vale do Sousa and Tamega. From February 2008 to January
      2009, 18653 urine cultures were analyzed. From these cultures 1037 were positive.
      From this total of positive cultures, 18,3% were from males and 81.7% were from
      females. In bacteriological positive tests, 23 different strains of
      microorganisms were found. It was verified that the most frequent microorganism
      was Escherichia coli, followed by Proteus mirabilis, Klebsiella pneumoniae,
      Enterococcus faecalis and Pseudomonas aeruginosa. For antimicrobial
      susceptibility it was verified that Escherichia coli showed low susceptibility to
      amoxicillin and cotrimoxazole. Proteus mirabilis showed good susceptibility to
      cefotaxime and low to cotrimoxazole, amoxicillin and ciprofloxacin. For
      Klebsiella pneumoniae was found only a reasonable susceptibility to gentamicin
      and Enterococcus faecalis showed amoxicillin susceptibility. Pseudomonas
      aeruginosa showed low susceptibility to all antibiotics analyzed with the
      exception of the combination piperacillin/tazobactam. In conclusion, this study
      shows that Escherichia coli, Proteus mirabilis and Klebsiella pneumoniae are the
      three main microorganisms that causes urinary infections in the region of Vale do
      Sousa and Tamega. Therefore, the antimicrobial empirically used must have a
      spectrum against enterobacteria, because they are the most likely to be present
      in urinary tract infections acquired in the community. A periodic analysis of the
      susceptibility profile should be performed over time for each region in order to
      help in the beginning of the empirical antimicrobial treatment.

PMID- 20687993
TI  - [Radiosurgery in the treatment of cerebral arteriovenous malformations].
AB  - Stereotactic radiosurgery is one of the principle treatment options for small
      cerebral arteriovenous malformations, even in eloquent locations. Complete
      obliteration mainly depends on the applied single dose and treatment volume,
      although other potential factors may interfere. The risk of intracranial
      hemorrhage after radiosurgery is related to the obliteration status and depends
      on the size and volume of cerebral arteriovenous malformations. Radiosurgery has
      shown to be effective with minimum morbidity. According to appropriate criteria
      as far as characteristics of cerebral arteriovenous malformations are concerned,
      and, balancing dose prescription and optimum planning, radiosurgery results are
      undeniably encouraging.

PMID- 20687994
TI  - [Personality and transplantation].
AB  - The association between personality and medical health has been subject of
      several studies. The most accepted theoretical models of personality, in this
      context, are of two kinds: Three factor model (neuroticism, extraversion
      epsicoticism) and five factor model (neuroticism, extraversion, consciousness,
      agreeableness, and openess to experience). There are three ways which can explain
      the interaction between personality and medical illness: Hyperactivity induced by
      personality, personality and illness independent predisposition, non-healthy
      behaviours induced by personality. There are several ways of assessing
      personality in medical illness: taxonomic vs dimensional approaches; Auto vs
      hetero evaluation; Specific vs non-specific methods. We analyse the arguments
      against and favourable to any of these approaches. Some of the most used
      instruments to assess personality in medical context are the NEOPI versions
      (original NEO-PI, NEO-PI-R, NEO-FFI-60). NEO-PI-R and NEO-FFI-60 are validated to
      the Portuguese population. According to the few published studies assessing
      personality in transplanted patients we concluded that neuroticism was associated
      to a poor quality of life (physical, mental, social) in post-transplantation
      period; extraversion to a better quality of life (physical, mental, social); type
      D personality to a worse quality of life and a increased mortality and rejection
      after transplantation. We also concluded that personality disorders were not
      associated to an increase of alcohol consumption in alcohol liver disease
      transplanted patients.

PMID- 20687995
TI  - [Immunology of dental caries].
AB  - Dental carie is the most common infectious disease in humans. In the past
      decades, it has been described as a multifactorial condition, where diet and the
      immune response are main factors for the establishment of the disease. The
      authors approach the formation of the bacterian biofilm, the host's immune
      response, according to its maturation and deficiencies, and the current research
      to find a preventive intervention for this disease.

PMID- 20687996
TI  - [Cardiovascular risk in HIV infected patients].
AB  - The increased cardiovascular risk has been implicated in both HIV infection and
      antirretroviral therapy. The endothelial dysfunction triggered by the infection
      and the metabolic abnormalities associated with therapy predispose to premature
      atherosclerosis. The recognition of the increased cardiovascular risk in these
      patients will allow more appropriate prevention strategies, as well as therapy
      optimization with lipid-lowering agents and antirretroviral therapy modification.

PMID- 20687997
TI  - [Renin-angiotensin-aldosterone system (RAAS) and its pharmacologic modulation].
AB  - The renin-angiotensin-aldosterone system (RAAS) is a neuroendocrine complex
      system that regulates the modulation of salt and water homeostasis, and
      regulation of blood pressure. Through its multiple interactions it protects the
      endothelium, heart, brain and kidney. In addition, the RAAS regulates the
      vascular response to injury and inflammation. Chronic activation/dysregulation of
      the RAAS leads to hypertension and perpetuates a cascade of proinflammatory,
      prothrombotic and atherogenic effects associated with endorgan damage (heart,
      brain, kidney, endothelium). Consequently, the RAAS is an important therapeutic
      target in these situations. This article presents an overview of physiology,
      pathophysiology and pharmacologic modulation of the RAAS.

PMID- 20687998
TI  - [Attention deficit hyperactivity disorder (ADHD) in children: neurobiological
      aspects, diagnosis and therapeutic approach].
AB  - INTRODUCTION: The attention deficit hyperactivity disorder (ADHD) is usually
      associated to child development, presenting a strong neurobiological influence
      and being, thus, mostly common in childhood. This disorder is characterized by a
      persistent pattern of lack of attention and/or by hyperactivity and impulsivity.
      OBJECTIVE: To conduct a systematic literature review on ADHD in children,
      focusing neurobiological aspects, diagnosis and therapeutic approaches.
      METHODOLOGY: This is a literature review about ADHD in childhood, from 1994
      through 2008. The neurobiological mechanisms that participate in ADHD are
      complex, involving the dopaminergic, noradrenergic and serotonergic systems. The
      diagnosis of ADHD must be based on the clinical behavior, since there is no
      biological marker defined. Metilfenidate is the main drug used for children's
      treatment. CONCLUSION: The search for relief of ADHD symptoms ought to be based
      on organic treatments, other specific treatments using medications or
      neurofeedbacks, as well as behavior therapies.

PMID- 20687999
TI  - [Fetopathy associated with exposure to angiotensin converting enzyme inhibitors].
AB  - Angiotensin Converting Enzyme Inhibitors (ACEI) are commonly used
      antihypertensive drugs, although contraindicated during pregnancy by fetopathy
      association such as renal dysgenesis, oligohydramnios, hipocalvaria, pulmonary
      hypoplasia, intrauterine growth restriction, and neonatal anuric renal failure.
      The authors present a clinical report of a child that developed neonatal anuric
      renal failure with peritoneal dialysis support by an in uterus exposure to ACEI
      with very good recovery. This case and literature review states the need to avoid
      ACEI prescription to Young women and it's suspension as soon as possible during
      pregnancy.

PMID- 20688000
TI  - [Hepatic granulomas in a feverish patient].
AB  - Fever of unknown origin is a diagnostic challenge. When the diagnosis remains
      elusive despite extensive non-invasive diagnostic studies, it can be necessary to
      conduct more invasive procedures, such as liver biopsy. We report a male with
      fever of unknown origin who had tender enlarged liver and raised liver enzymes
      whose hepatic biopsy disclosed epithelioid granulomas, with the etiological
      diagnosis made by the positivity of Coxiella burnetii serology.

PMID- 20688001
TI  - [Ulcerative colitis initial presentation with multiple extra-intestinal
      manifestations].
AB  - Multiple extraintestinal diseases are present in 0.3- 4.5 % of inflammatory bowel
      disease patients. A 39-year-old woman was admitted with a 3 months history of
      cervicalgia with functional incapacity, asthenia, tibio-tarsal bilateral
      arthritis and bloody diarrhoea. She had ferropenic anemia, SR-120 mm, creatinine
      clearance-42 mL/min, proteinuria-1.2 g/24h. Colonoscopy with biopsy showed active
      ulcerative rectossigmoiditis. She had bilateral sacroileitis more pronounced at
      the right side which was suggestive of ankylosing spondylitis. HLA B27 was
      positive. Because of colestasis, colangio-MRI and CPRE were done and were
      suggestive of primary sclerosing colangitis. Renal disease was interpreted as an
      analgesic nephropathy versus glomerulonephritis associated with ulcerative
      colitis. Cardiac ecodoppler showed pericardial thickening with a thin pericardial
      effusion. Full improvement of gastrointestinal complaints was observed with 5-ASA
      topic enemas, sulfassalazine, corticosteroids and azathioprine and full remission
      of ankylosing spondylitis with adalimumab. This case illustrates extraintestinal
      wide involvement as the initial presentation of ulcerative colitis, remarking its
      systemic nature.

PMID- 20688002
TI  - [Pontine and extrapontine myelinolysis].
AB  - INTRODUCTION: Myelinolysis is defined as acute demyelinating disorder, associated
      with flaccid quadriplegia, speech and swallowing impairment. The pathogenesis is
      usually related to hydroelectrolytic imbalance, particularly with severe
      hyponatremia and its rapid correction. The imagiologic diagnostic is commonly
      done by magnetic resonance imaging. AIM: The authors present a clinical case
      focusing on the follow up, rehabilitation program, and giving importance to
      functionality gains. The main clinical intercurrences related to the late
      diagnosis are also reported. CLINICAL CASE: A female patient with documented past
      psychiatric history and polidipsia was admitted with repeated seizures
      unsuccessfully controlled by drugs. Hyponatremia was identified and corrected.
      After the correction, a quadriplegia and a generalized hypotonia were noticed and
      the patient underwent magnetic resonance imaging. The imaging findings were
      consistent with the diagnosis of central pontine and extrapontine myelinolysis.

PMID- 20688003
TI  - [Anticonvulsant hypersensitivity syndrome in children].
AB  - Anticonvulsant hypersensitivity syndrome, or DRESS (Drug Rash with Eosinophilia
      and Systemic Symptoms), is a rare multisystem disorder, potentially fatal, that
      occurs after exposure to antiepileptic drugs, mainly aromatic ones. Clinically,
      this condition is recognized by the classic triad of fever, rash and internal
      organ involvement that usually develops 1 to 12 weeks after initiation of
      therapy. We report a case of a child treated with sodium valproate for epilepsy
      that showed a febrile rash 4 weeks after being medicated with phenobarbital.
      Laboratory testing revealed leukocytosis with eosinophilia elevated C-reactive
      protein and liver enzymes. Phenobarbital was suspended, with slow full recovery.
      This syndrome may mimic infectious, immunologic and neoplastic conditions, which
      may delay the correct diagnosis, but must be excluded in the presence of
      characteristic clinical features and drug exposition.

PMID- 20688004
TI  - [Successful caspofungin treatment of invasive refractory candidiasis in the
      extremely low birthweight neonate].
AB  - INTRODUCTION: Multiresistant Candida septicaemia is an increasing problem in
      Neonatal Intensive Care Units worldwide. Caspofungin is a new antifungal drug
      licensed in Portugal for use in children since September 2008, with limited
      experience in newborns. CASE REPORT: Preterm female, 26 weeks gestational age,
      born by vaginal delivery, with 780g birthweight and Apgar score 8/9. The newborn
      developed a mucocutaneous candidiasis at day 8 of life which was treated with
      oral nystatin and topic clotrimazol. Clinical and laboratory deterioration
      occurred at day 15 of life with Candida albicans sepsis being diagnosed. Therapy
      with amphotericin B liposome was started but the clinical condition and
      candidemia persisted. Treatment with caspofungin was initiated at day 28 of life
      and continued for 28 days. There was an improvement of the clinical condition and
      the blood cultures became negative. The child was discharged at the 80th of life
      with no evident clinical problems. The long term follow-up revealed bilateral
      deafness. COMMENT: This case reveals that caspofungin may be a useful choice for
      invasive refractory candidiasis in the neonate, especially in the extremely low
      birthweight neonate and in life-threatening situations. Long term follow-up is of
      great importance in order to document adverse effects not apparent at the
      neonatal period.

PMID- 20688005
TI  - [Genital tuberculosis: a rare cause of postmenopausal bleeding].
AB  - BACKGROUND: Tuberculosis remains a global health problem, being the genitourinary
      tract the second most common site for tuberculosis infection after the lungs.
      Genital tuberculosis is now undergoing a worrying recrudescence. CASE REPORT: We
      report two cases of postmenopausal women who presented with vaginal bleeding.
      General physical and gynecological examination detected no abnormality.
      Transvaginal pelvic ultrasound showed fluid in the endometrial cavity in both
      cases. The office hysteroscopy was suggestive of focal endometrial thickness and
      an endometrial biopsy was performed. The histopathologic examination of biopsies
      found epithelioid cell granulomas without malignant cells. Culture of the
      endometrium was positive for Mycobacterium tuberculosis. Involvement of other
      systems was not detected. The patients started receiving antituberculosis
      treatment. CONCLUSION: Genital tuberculosis is rare in postmenopausal women and
      responsible for only approximately 1% of postmenopausal bleeding. However it is a
      curable disease and an early diagnosis is important and may prevent unnecessary
      invasive procedures for the patient.

PMID- 20688006
TI  - [Warfarin hipersensitivity: how to deal with it?].
AB  - The authors report a clinical case of warfarin hypersensitivity noticed when a
      patient, with thromboembolic risk, was submitted to warfarin. She was found to be
      heterozigotic to -1639G>A (gene VKORC1) and homozygotic to 1075A>C (genotype
      CYP2C9*3/*3). In this article the warfarin pharmacodinamics and its role over
      Vitamin K is revisited. It includes some suggested indications for investigating
      genetic polymorphisms, in order to avoid complications associated with warfarin.

PMID- 20688007
TI  - [Metastatic calcification detected on bone scintigraphy].
AB  - PURPOSE: To show the value of bone scintigraphy in the diagnosis of metastatic
      calcification in end-stage renal insufficiency. MATERIAL AND METHODS: The authors
      present a fifty-one-year-old male with terminal renal insufficiency of
      hypertensive renovascular etiology, on hemodialysis for the last 10 years,
      referred for a bone scan because of osteoarticular complaints, and no other
      associated symptoms or findings on physical examination. RESULTS: Whole body bone
      scintigraphy images (HMDP-99mTc, 925MBq), showed increased uptake in the lower
      half of both lungs, the stomach and renal parenchyma, compatible with metastatic
      calcification. CONCLUSIONS: Bone scintigraphy, due to its high sensitivity, even
      in the detection of early changes, might be a useful instrument in the initial
      evaluation and follow-up of patients with high risk of developing metastatic
      calcification.

PMID- 20688008
TI  - [Haemophilus influenzae meningitis in adolescence].
AB  - A 13-year-old girl presented with a one-day history of severe and persistent
      headache, high fever, vomiting and nuchal rigidity. Previous history of cranial
      traumatism when she was six and hypoacusis since she was an infant. Cerebrospinal
      fluid (CSF) culture revealed Haemophilus influenzae non typable. Clinical course
      was positive. Investigation of immunologic cause was negative. Imaging
      investigation (cranial computed tomography scan and magnetic resonance imaging)
      revealed traumatic frontal cranial deformity and meningocele. Non typable
      Haemophilus infuenzae is a rare cause of meningitis, unless predisposing factor
      is present.

PMID- 20688009
TI  - Sugammadex for the reversal of muscle relaxation in general anaesthesia: a
      systematic review and economic assessment.
AB  - BACKGROUND: Sugammadex (Bridion) is a newly developed agent for the reversal of
      neuromuscular blockade (NMB) induced by rocuronium or vecuronium. Sugammadex can
      reverse profound blockade and can be given for immediate reversal and its use
      would avoid the potentially serious adverse effects of the currently used agent,
      succinylcholine. Also, sugammadex can reverse NMB more quickly and predictably
      than existing agents. OBJECTIVES: To determine the clinical effectiveness and
      cost-effectiveness of sugammadex for the reversal of muscle relaxation after
      general anaesthesia in UK practice following routine or rapid induction of NMB.
      DATA SOURCES: Medical databases [including MEDLINE, EMBASE, CINAHL, Science
      Citation Index, BIOSIS and Cochrane Central Register of Controlled Trials
      (CENTRAL), conference proceedings, internet sites and clinical trials registers]
      were searched to identify published and unpublished studies. The main searches
      were carried out in May 2008 and supplemented by current awareness updates up
      until November 2008. REVIEW METHODS: For the clinical effectiveness review,
      randomised controlled trials of sugammadex against placebo or an active
      comparator (neostigmine + glycopyrrolate) for the reversal of moderate or
      profound NMB and for immediate reversal (spontaneous recovery from
      succinylcholine-induced blockade) were included. The primary effectiveness
      outcome was speed of recovery from NMB, as measured by objective monitoring of
      neuromuscular function. For the cost-effectiveness review, a de novo economic
      assessment considered the routine induction of NMB and the rapid induction and/or
      reversal of NMB, and threshold analyses were carried out on a series of pairwise
      comparisons to establish how effective sugammadex needs to be to justify its
      cost. RESULTS: The review of clinical effectiveness included four randomised
      active-control trials of sugammadex, nine randomised placebo-controlled trials
      and five studies in special populations. A total of 2132 titles and abstracts and
      265 full-text publications were screened. The included trials indicated that
      sugammadex produces more rapid recovery from moderate or profound NMB than
      placebo or neostigmine. Median time to recovery from moderate blockade was 1.3
      1.7 minutes for rocuronium + sugammadex, 21-86 minutes for rocuronium + placebo
      and 17.6 minutes for rocuronium + neostigmine. In profound blockade, median time
      to recovery was 2.7 minutes for rocuronium + sugammadex, 30 to > 90 minutes for
      rocuronium + placebo, and 49 minutes for rocuronium + neostigmine. Results for
      vecuronium were similar. In addition, recovery from NMB was faster with
      rocuronium reversed by sugammadex 16 mg/kg after 3 minutes (immediate reversal)
      than with succinylcholine followed by spontaneous recovery (median time to
      primary outcome 4.2 versus 7.1 minutes). The evidence base for modelling cost
      effectiveness is very limited. However, assuming that the reductions in recovery
      times seen in the trials can be achieved in routine practice and can be used
      productively, sugammadex [2 mg/kg (4 mg/kg)] is potentially cost-effective at its
      current list price for the routine reversal of rocuronium-induced moderate
      (profound) blockade, if each minute of recovery time saved can be valued at
      approximately 2.40 pounds (1.75 pounds) or more. This is more likely to be
      achieved if any reductions in recovery time are in the operating room (estimated
      value of 4.44 pounds per minute saved) rather than the recovery room (estimated
      value of 0.33 pounds per minute saved). The results were broadly similar for
      rocuronium- and vecuronium-induced blockade. For rapid reversal of NMB it
      appeared that any reduction in morbidity from adopting sugammadex is unlikely to
      result in significant cost savings. LIMITATIONS: The evidence base was not large
      and many of the published trials were dose-finding and safety studies with very
      small sample sizes. Also, some relevant outcomes, in particular patient
      experience/quality of life and resources/costs used, were either not investigated
      or not reported. In addition, it is likely that the patients included in the
      efficacy trials were relatively young and in good general health compared with
      the overall surgical population. Regarding the economic evaluation, there appears
      to be no evidence linking measures of clinical efficacy to patients' health
      related quality of life and mortality risks. CONCLUSIONS: Sugammadex may be a
      cost-effective option compared with neostigmine + glycopyrrolate for reversal of
      moderate NMB and also provides the facility to recover patients from profound
      blockade. Rocuronium + sugammadex could be considered as a replacement for
      succinylcholine for rapid induction (and reversal) of NMB, although this may not
      be a cost-effective option in some types of patient at current list prices for
      sugammadex. Considerable uncertainties remain about whether the full benefits of
      sugammadex can be realised in clinical practice.

PMID- 20688010
TI  - Dental education in Pakistan: current trends and practices.

PMID- 20688011
TI  - Comparison of the impaired fasting blood glucose in young healthy individuals
      with diabetic and non-diabetic first degree relatives.
AB  - OBJECTIVE: To compare the fasting blood glucose (FBG) level in the healthy young
      individuals with diabetic first degree relatives considered as high risk and non
      diabetic first degree relative considered as low risk. STUDY DESIGN: Cross
      sectional, comparative study. PLACE AND DURATION OF STUDY: Department of
      Medicine, Liaquat University of Medical and Health Sciences Hospital,
      Hyderabad/Jamshoro, from January to November 2008. METHODOLOGY: Individuals aged
      between 20-40 years were selected and divided into two groups. Group A was
      considered as high risk included non-diabetic young offspring's of type-2
      diabetic parents. Group B was considered as low risk nondiabetic offsprings of
      non-diabetic family (control group), of same age and gender. Fasting blood
      glucose levels were measured in each individual. Exclusion criteria were known
      diabetes and pregnancy. Mean glucose levels were compared using t-test.
      Proportions of impaired glucose level versus positive family history were
      compared using chi-square test. Significance was considered at p<0.05. RESULTS:
      There were a total of 500 subjects including 250 in each group with equal gender
      distribution in each group. The mean age was 27.46+/-5.71 years. Mean FBG was
      87.4+/-13.82 mg/dl in group A and 77.7+/-15.18 mg/dl in group B (p=0.001). Twenty
      five (10%) in group A and five (2%) in group B individuals showed impaired
      fasting blood glucose (p=0.001). CONCLUSION: Impairment of fasting blood glucose
      was with family history of type-2 Diabetes mellitus in comparison to those
      without type-2 Diabetes mellitus.

PMID- 20688012
TI  - Self expandable metallic stent endoscopic insertion in esophageal cancer.
AB  - OBJECTIVE: To determine the safety of self expandable metallic stent (SEMS)
      placement under endoscopic guidance without fluoroscopy. STUDY DESIGN: Quasi
      experimental study. PLACE AND DURATION OF STUDY: Section of Gastroenterology and
      Hepatology, Departments of Medicine, Isra University Hospital and Liaquat
      University of Medical and Health Sciences (LUMHS), Hyderabad, from April 2006 to
      March 2009. METHODOLOGY: In 80 patients with inoperable carcinoma of esophagus,
      SEMS made-up of nickel titanium alloy and mesh shaped with distal release system
      were placed without the use of fluoroscope under endoscopic guidance. Patients
      with proximal location of tumour in esophagus were excluded. They were followed
      at one week after deployment. All the complications were recorded. Dysphagia
      score was assessed before and after stent placement. Mean pre- and poststenting
      scores were compared using t-test. RESULTS: Fluoroscopy was needed in only 2
      patients. In 75 patients the stent was successfully placed with endoscope control
      only, without fluoroscope. Dysphagia score improved significantly from 4.26+/
      1.07 before stenting to 1.02+/-0.57 later, (p<0.001). Minor complications like
      retrosternal pain occurred in 30 (37.5%) patients and major complications in 8
      (10.0%) patients amongst which 4 (5.0%) developed upper gastrointestinal bleeding
      and 4 patients (5.0%) had aspiration. CONCLUSION: Insertion of self expandable
      metallic stent in esophageal carcinoma without fluoroscope was safe and effective
      in relieving dysphagia at short term follow-up.

PMID- 20688013
TI  - Influence of ASA score and Charlson Comorbidity Index on the surgical site
      infection rates.
AB  - OBJECTIVE: To compare the frequencies of surgical site infections (SSI) in ASA
      class-I (American Society of Anaesthesiologists-I) with ASA class II-III and CCI
      0 (Charlson Co-morbidity Index-0) with CCI 1-6 in clean (C) and clean
      contaminated (CC) surgeries. STUDY DESIGN: Analytical study. PLACE AND DURATION
      OF STUDY: This study was conducted in a General Surgical Unit of Khyber Teaching
      Hospital, Peshawar, from December 2008 to April 2009. METHODOLOGY: A total of 310
      clean and clean contaminated general surgical interventions with pre-operative
      ASA score of I-III, were included in the study, excluding anal and cystoscopic
      procedures. On the basis of past medical record, patients were grouped into ASA-I
      (patients without any co-morbidity) and ASA II-III (patients with co-morbidities)
      on the basis of their ASA score pre-operatively. In the same way patients were
      divided into CCI-0 (patients without co-morbidities) and CC 1-6 (patients with co
      morbidities) according to CCI score. All the patients were operated in the same
      environment by the same set of surgeons. Postoperatively the surgical wounds were
      observed for SSI by using ASEPSIS daily scoring system for one month
      prospectively. SSI rates in ASA-I was compared with SSI rates in ASA II-III.
      Similar comparison of SSI rates was performed in CCI-0 and CCI 1-6. Data was
      tested by using the Fisher's exact test with confidence interval of 95%. RESULTS:
      The overall SSI rate was 6.1% (n=19) with 4.23% (n=5) in clean cases (C) and
      7.29% (n=14) in clean contaminated cases (CC). There were significantly higher
      surgical site infection rates among patients in ASA II-III than those with ASA-I
      in clean contaminated surgeries (p=0.003). There were also significantly higher
      surgical site infection rates among patients with CCI score 1-6 than those with
      CCI-0 in clean (p=0.024) and clean contaminated (p=0.002). CONCLUSION: American
      Society of Anaesthesiologists (ASA) score and Charlson comorbidity index (CCI)
      has strong influence on SSI rates in clean and clean contaminated cases.
      Patients' with co-morbidities undergoing clean and clean contaminated general
      surgical procedures have greater SSI rates than those without any co-morbidity.

PMID- 20688014
TI  - Hepatocellular carcinoma: a clinicopathological study.
AB  - OBJECTIVE: To describe the clinico-pathological and radiological profile of
      hepatocellular carcinoma. STUDY DESIGN: A case series. PLACE AND DURATION OF
      STUDY: Medical Unit-III Ward-7, Jinnah Postgraduate Medical Centre, Karachi, from
      January to December 2008. METHODOLOGY: All consecutive patients suspected of
      having hepatocellular carcinoma (HCC), were admitted and included in this study.
      Diagnosis of HCC was established by clinical, biochemical, ultrasonographic and
      histopathologic findings. Patients with primary carcinoma elsewhere in the body,
      metastatic in the liver, fibrolamellar carcinoma and benign tumours were excluded
      from the study. At ultrasonography, the details of tumour size and number, portal
      vein thrombosis and presence of ascites were recorded. Patients were staged
      according to Okuda staging system. Results were described in mean and percentage
      values. RESULTS: There were 82 patients with hepatocellular carcinoma including
      58 males and 24 females, with male to female ratio of 2.8:1. The mean age of
      patients was 56.24+/-13.65 years. Right hypochondrial pain was the main symptom
      in 52 (63.4%) patients. The duration of symptoms varied from 1 month to 2 years.
      Tumour size was larger than 50% of liver size in 42 (51.2%) with portal vein
      thrombosis in 10 (12.19%). Anti HCV was positive in 44 (53.7%), HBsAg in 26
      (31.7%) and both were found positive in 2 (2.44%) patients. Ten patients (12.2/%)
      found negative both for anti-HCV and HBsAg. According to Okuda staging system 18
      patients had stage 1, 50 had stage 2 and 14 had stage 3 hepatocellular carcinoma.
      CONCLUSION: The mean age of presentation of hepatocellular carcinoma was younger
      as compared to western countries with potentially large non-resectable lesions.
      Chronic hepatitis C and B was found to be the major known factors. Patients with
      chronic hepatitis C and B should undergo vigorous HCC surveillance to detect
      early, potentially respectable HCC.

PMID- 20688015
TI  - Precipitating factors and the outcome of hepatic encephalopathy in liver
      cirrhosis.
AB  - OBJECTIVE: To determine precipitants of hepatic encephalopathy (HE) and their
      impact on hospital stay and mortality. STUDY DESIGN: Cross-sectional, analytical
      study. PLACE AND DURATION OF STUDY: The Aga Khan University Hospital, from
      January 2005 to December 2007. METHODOLOGY: Consecutive patients admitted with
      different grades of HE were evaluated between January 2005 and December 2007. The
      precipitants of HE were correlated with the different grades of HE, and length of
      hospital stay and mortality. Chi-square test was used to compare the proportion
      of precipitating factors versus hospital stay and grade with significance at
      p<0.05. RESULTS: Of the 404 patients 252 (62%) were males. Hepatitis C virus was
      the cause of cirrhosis in 283 (70%); Child Turcotte Pugh (CTP) class C was
      present in 317 (78%) patients. On presentation, 17% patients had grade 1 HE while
      44%, 29% and 10% had grades 2, 3 and 4 respectively. The most common precipitant
      of HE was spontaneous bacterial peritonitis in 83 (20.5%), constipation in 74
      (18.3%) and urinary tract infection in 62 (15.3%). One hundred and forty (35%)
      patients had (3) 2 precipitating factors while no precipitant was noted in 50
      (12%) patients. Mean hospital stay was 4+/-3 days. The lesser the number of
      precipitants, shorter was the length of stay (p<0.01) and lesser was the grade of
      HE (p=0.025). Complete reversal of HE was noted in 366 patients (91%) while the
      remaining had grade 1 HE on discharge. Nine (2.2%) patients died during the
      hospital stay. No mortality was noted in patients without precipitants.
      CONCLUSION: Patients presenting with (3) 2 precipitating factors and advanced
      grade of HE had a prolonged hospital stay. Moreover, patients without
      precipitants had better outcomes.

PMID- 20688016
TI  - Comparison of heat induced antigen retrieval techniques for immune-histochemical
      estrogen receptor expression in ductal carcinoma of breast in females.
AB  - OBJECTIVE: To compare immunohistochemical estrogen receptor expression on
      formalin-fixed, paraffin-embedded breast carcinoma tissue sections by using
      regular, extended microwave heating and pressure cooker technique for heat
      induced antigen retrieval. STUDY DESIGN: Quasi experimental study. PLACE AND
      DURATION OF STUDY: Department of Histopathology, Armed Forces Institute of
      Pathology, Rawalpindi, from August 2006 to July 2007. METHODOLOGY: The study was
      conducted on 40 cases of breast carcinoma diagnosed on histopathology and
      selected by convenience sampling. One section each of the tumour was separately
      subjected to regular microwave heating (10 minutes), extended microwave heating
      (20 minutes) and pressure cooker (heating for 2 minutes after reaching full
      pressure). A nuclear staining of >10% cells with moderate intensity was
      considered positive and frequency of ER expression by each technique was compared
      statistically. Sensitivity and specificity of the techniques was determined using
      pressure cooker technique as the gold standard for this study. RESULTS: Out of 40
      cases, ER expression in 24 (60%) cases was seen by microwave regular heating
      (MRH) and in 30 (75%) cases by microwave extending heating (MEH) technique.
      Pressure cooker (PC) technique for antigen retrieval demonstrated 34 (85%) cases
      with ER expression. Out of 16 which were negative by MRH technique, 6 became
      positive by MEH while 10 became positive by PC. Statistically significant
      difference in ER expression by PC and MEH technique was seen in comparison to MRH
      with a p-value of <0.05. Moreover, 4 cases which were negative by MEH technique
      turned positive for ER expression by PC. MRH and MEH had 100% specificity but
      sensitivity was 70.6% and 88.2% respectively taking PC technique as gold standard
      with diagnostic accuracy of MEH as 90% and MRH as 75%. CONCLUSION: Pressure
      cooker antigen retrieval technique is a better method than microwave heating. The
      increase in duration of heating improves the percentage of positive cells as well
      as intensity of ER immuno-staining which entitles breast cancer patient to
      benefit from ER positive treatment protocols which have better prognosis.

PMID- 20688017
TI  - Association of raised intraocular pressure and its correlation to the energy used
      with raised versus normal intraocular pressure following Nd: YAG laser posterior
      capsulotomy in pseudophakes.
AB  - OBJECTIVE: To determine the frequency of raised intraocular pressure (IOP) after
      Nd: YAG laser posterior capsulotomy and its association with the energy used with
      raised versus normal intraocular pressure in pseudophakes. STUDY DESIGN:
      Comparative, cross-sectional study. PLACE AND DURATION OF STUDY: Ophthalmology
      Department, PNS Shifa Hospital, Karachi, from August 2008 to February 2009.
      METHODOLOGY: Pseudophakes having poor vision due to posterior capsular
      opacification (PCO) in an otherwise normal looking eye and intraocular pressure
      between 10-20 mmHg were included in the study. Patients with diabetic
      retinopathy, corneal diseases, inflammatory eye diseases, posterior segment
      surgery, glaucoma, trabeculectomy, maculopathy and any systemic disease were
      excluded from the study. Particulars of the eligible patients and pre-laser
      intraocular pressure were entered in specially designed proforma. Nd: YAG laser
      posterior capsulotomy was done. Laser energy used was noted and then their post
      laser intraocular pressure was checked after 4 hours. Unpaired t-test was used
      for comparison of means of IOP and energy levels. Chi-square test was applied to
      compare the proportions of patients with raised and the normal IOP with YAG laser
      energy used during posterior capsulotomy. RESULTS: Raised intraocular pressure
      (IOP>or=5 mmHg from the baseline) after Nd: YAG laser posterior capsulotomy was
      noted in both the 'low energy' and the 'high energy' groups but it was more
      common in the 'high energy' group (p<0.001, r=0.512). CONCLUSION: Higher YAG
      laser energy has significantly higher chances of raising IOP. Hence, it was
      recommended that each patient undergoing Nd: YAG laser capsulotomy should receive
      minimum possible laser energy and must be followed up for raised intraocular
      pressure.

PMID- 20688018
TI  - Prevalence of type-II diabetes mellitus and diabetic retinopathy: the Gaddap
      study.
AB  - OBJECTIVE: To determine the frequency of type-II Diabetes mellitus (DM) in the
      endogenous population of Gaddap town and also to evaluate the status of Diabetic
      retinopathy (DR) in this group. STUDY DESIGN: Descriptive study. PLACE AND
      DURATION OF STUDY: Isra Postgraduate Institute of Ophthalmology, Al-Ibrahim Eye
      Hospital, Karachi, from January 2006 till December 2008. METHODOLOGY: This
      community based study of subjects of either gender was carried out in the Gaddap
      town. Three primary eye care centres were established in the existing primary
      health care (PHC) facilities, to screen the target Population aged 30 years and
      above, and who met other inclusion criteria for DM and DR respectively. Patients
      requiring intervention were managed accordingly. Data was entered and analyzed
      using Microsoft Visual Basic 6 and Microsoft Access. RESULTS: Out of the cohort
      of 19211 subjects, 1677 patients were found Diabetic, giving the prevalence of DM
      in Gaddap town at 8.73%, with 1258 (6.55%) known and 419 (2.18%) newly diagnosed
      cases. DR was seen in 460 (27.43%) of the Diabetic cases with 126 (7.51%)
      patients requiring urgent intervention for vision threatening complications.
      CONCLUSION: The result validates the importance of early screening of DR in
      people suffering from DM for possible management and prevention of sight
      threatening complications in the early stage of the disease and advocates the
      inclusion of primary eye care as a part of PHC system.

PMID- 20688019
TI  - Comparison of three mixed dentition analysis methods in orthodontic patients at
      AKUH.
AB  - OBJECTIVE: To compare the actual sum of canine and premolars and that predicted
      from three mixed dentition prediction methods in orthodontic patients at the Aga
      Khan University Hospital (AKUH), Karachi. STUDY DESIGN: Cross-sectional
      comparative study. PLACE AND DURATION OF STUDY: Orthodontic clinic at the Aga
      Khan University Hospital from June 2002 to December 2007. METHODOLOGY: Data were
      collected using pretreatment records including orthodontic files and plaster
      casts of 121 orthodontic patients. Digital caliper was used to measure the
      mesiodistal widths of permanent teeth from 1st molar to 1st molar in mandibular
      arch, and central incisors and 1st molars in maxillary arch. The methods of
      Tanaka and Johnston, Moyers, and Bernabe and Flores-Mir were used to predict the
      mesiodistal widths of the canine and premolars. Comparison between the actual and
      predicted sum of the mesiodistal widths of canine and premolars was made for each
      prediction method, using paired sample t-test. RESULTS: There were 45 males and
      76 females with average ages of 13.3+/-1.3 and 13.4+/-0.8 years respectively. For
      males statistically significant differences were found for Moyers at the 75th
      percentile and Bernabe and Flores-Mir method whereas for females only the Bernabe
      and Flores-Mir's method showed significant results. However, no significant
      difference was found in both genders for Tanaka and Johnston method. CONCLUSION:
      In the studied orthodontic patients for males Moyers 50th percentile and Tanaka
      and Johnston methods could be used; while for females Moyers 75th percentile and
      Tanaka and Johnston methods were applicable for mixed dentition analysis.

PMID- 20688020
TI  - Post-tonsillectomy pain and bupivacaine, an intra individual design study.
AB  - OBJECTIVE: To compare whether an individual could appreciate the pain relief, if
      any, in either one of his/her tonsillar fossa topically suffused with a local
      anaesthetic (bupivacaine). STUDY DESIGN: Randomized controlled trial. PLACE AND
      DURATION OF STUDY: Department of ENT/Head and Neck Surgery, Combined Military
      Hospital, Peshawar, from January to June 2007. METHODOLOGY: Forty-six patients of
      either gender, aged 10-42 years undergoing tonsillectomy for recurrent
      tonsillitis were enrolled for this study. At the end of surgery, having secured
      haemostasis, one tonsillar fossa was randomly packed with a gauze piece soaked in
      3 ml of 0.5% bupivacaine for 5 minutes, while the other was not. Effects of
      postoperative analgesia were assessed using visual analogue scale (VAS) up to 8
      hours. RESULTS: Majority of the patients (85%, n=39) failed to experience an
      appreciable pain relief on the side of local anaesthetic (bupivacaine)
      application (p=0.006). CONCLUSION: Topical application of local anaesthetic
      (bupivacaine) confers no appreciable pain control in post-tonsillectomy patients.

PMID- 20688022
TI  - Single lung ventilation in a young child for repair of coarctation of aorta.
AB  - Single lung ventilation in small children is extremely challenging. In this case,
      a paediatric bronchial blocker was successfully inserted in a 19-month-old child
      to provide single lung ventilation using a modified insertion technique. It
      provided excellent working conditions during thoracotomy and our method of
      insertion may help in reducing the cost.

PMID- 20688021
TI  - Post-tuberculous chronic obstructive pulmonary disease.
AB  - OBJECTIVE: To determine the frequency of chronic obstructive pulmonary disease
      (COPD) as a sequel of treated pulmonary tuberculosis. STUDY DESIGN: A case
      series. PLACE AND DURATION OF STUDY: Department of Pulmonology, Military
      Hospital, Rawalpindi, from April to November 2007. METHODOLOGY: Forty seven
      adults, previously treated for pulmonary tuberculosis and presenting subsequently
      with chronic exertional dyspnoea for which no other alternate cause was found
      were included. Those having a probability of re-activated TB, having history of
      current or previous smoking or occupational exposure, asthmatics and cases of
      interstitial lung disease and ischemic heart disease were excluded. Pre- and post
      dilator FVC, FEV1 and FEV1/FVC were recorded in each case through simple
      spirometry on Spirolab-II-MIR S/N 507213. Stage and pattern of COPD was recorded.
      RESULTS: There were 76.5% (n=36) males. Mean age was 56.4 and 44.2 years in males
      and females respectively. Twenty six (55.3%) were found to have an obstructive
      ventilatory defect of different degrees: severe/stage III in 69.2% (n=18),
      moderate/stage II in 23.0 % (n=6) and mild/stage I in 5.9% (n=2). Fourteen
      (29.7%) were found to have a restrictive pattern and 7 (14.8%) revealed a mixed
      obstructive and restrictive pattern. CONCLUSION: Chronic obstructive pulmonary
      disease can occur as one of the chronic complications of pulmonary tuberculosis
      and the obstructive ventilatory defect appears more common among various
      pulmonary function derangements.

PMID- 20688023
TI  - Cutaneous CD30 positive anaplastic large cell lymphoma.
AB  - An adult Caucasian male presented with a solitary abscess-like lesion on his left
      thigh. The lesion later on ulcerated and developed a central eschar. The initial
      differential diagnoses included deep mycosis, insect bite reaction or atypical
      mycobacterial infection. Histology confirmed it to be a CD30 positive anaplastic
      large cell lymphoma. Haematologyoncology screen was carried out and the patient
      started on local field radiotherapy. Localized lymphomatous lesions can be
      treated with surgical excision or local radiotherapy. Systemic treatments are
      reserved for generalized disease. The prognosis depends on the extent of
      involvement.

PMID- 20688024
TI  - Quebec platelet disorder.
AB  - A case of Quebec platelet disorder is hereby reported. A 33 years old woman
      presented with history of epistaxis and gum bleeding since childhood and
      menorrhagia and bleeding per vaginum after puberty, also had history of excessive
      blood loss after birth of child. Her coagulation profile was normal but platelet
      function testing by platelet aggregation assay showed abnormal aggregation of
      platelet with epinephrine. This type of response is seen in "Quebec platelet
      disorder" which is a rare autosomal dominant disorder of platelet function
      characterized by increased bleeding after any injury or trauma.

PMID- 20688025
TI  - Deferasirox induced liver injury in haemochromatosis.
AB  - Durg-induced liver injury is a common side-effect of many medicines. It is
      particularly problem when the original condition under treatment is already
      causing liver damage. This report describes the hepatotoxicity induced by
      Deferasirox in a patient with haemochromatosis with a discussion of possible
      pathogenetic mechanism.

PMID- 20688026
TI  - Omental caking: a rare manifestation of malignant peripheral nerve sheath tumour.
AB  - Malignant peripheral nerve sheath tumour (MPNST) is a very rare tumour with an
      incidence of one per 100,000 and constitutes between 3 to 10% of all soft tissue
      sarcomas. Most of the sarcoma involve the extremities and retroperitoneal
      regions. However, this case presented with mass in left inguinal region and then
      spread rapidly to omentum, assuming the appearance of an omental cake. Mass
      responded well to chemotherapy comprising of Ifosfamide and Doxorubicin.

PMID- 20688027
TI  - Cervicofacial emphysema.
AB  - The case describes a young girl developing cervicofacial emphysema after fall.
      She presented in emergency with gradually worsening upper body swelling without
      any sign of distress. Swelling was found on the right side of the face, all
      around the neck and right arm with crepitus in all these areas. CT scanning of
      head, neck and chest were performed and a small area of communication between
      nasopharynx and the trapped air of subcutaneous emphysema was seen. Video
      endoscopy of the pharynx showed a tear in the nasopharyngeal mucosa acting as a
      one way valve leading to the development of cervicofacial emphysema.

PMID- 20688028
TI  - Characterization of a vancomycin intermediate-resistant Staphylococcus aureus
      isolated from a hospital.
AB  - A Vancomycin intermediate resistant strain of Staphylococcus aureus (S. aureus)
      labeled as CP2 (MIC 16 microg/ml) was isolated from an in-patient of local
      Cardiac Hospital of Karachi. CP2 showed typical characters of Vancomycin
      intermediate resistant S. aureus (VISA) i.e. high level of oxacillin resistance,
      thickened cell wall with rough surface and reduced autolytic activities
      associated with murein hydrolase (MH) enzyme. This strain may have acquired
      vancomycin resistance due to long term exposure to antibiotic during the
      treatment of the patient. Therefore, it implicates the importance of monitoring
      the usage and also to control of the abuse of antibiotics for prevention of any
      further proliferation of this type of notorious bugs.

PMID- 20688029
TI  - Research in radiology.

PMID- 20688030
TI  - Facilitating research through comprehensive cardiology clinical research
      database.

PMID- 20688031
TI  - Neuroscience in Pakistan: a neglected avenue.

PMID- 20688032
TI  - Prognostic significance of myocardial fibrosis in hypertrophic cardiomyopathy.
AB  - OBJECTIVES: We investigated the significance of fibrosis detected by late
      gadolinium enhancement cardiovascular magnetic resonance for the prediction of
      major clinical events in hypertrophic cardiomyopathy (HCM). BACKGROUND: The role
      of myocardial fibrosis in the prediction of sudden death and heart failure in HCM
      is unclear with a lack of prospective data. METHODS: We assessed the presence and
      amount of myocardial fibrosis in HCM patients and prospectively followed them for
      the development of morbidity and mortality in patients over 3.1 +/- 1.7 years.
      RESULTS: Of 217 consecutive HCM patients, 136 (63%) showed fibrosis. Thirty-four
      of the 136 patients (25%) in the fibrosis group but only 6 of 81 (7.4%) patients
      without fibrosis reached the combined primary end point of cardiovascular death,
      unplanned cardiovascular admission, sustained ventricular tachycardia or
      ventricular fibrillation, or appropriate implantable cardioverter-defibrillator
      discharge (hazard ratio [HR]: 3.4, p = 0.006). In the fibrosis group, overall
      risk increased with the extent of fibrosis (HR: 1.18/5% increase, p = 0.008). The
      risk of unplanned heart failure admissions, deterioration to New York Heart
      Association functional class III or IV, or heart failure-related death was
      greater in the fibrosis group (HR: 2.5, p = 0.021), and this risk increased as
      the extent of fibrosis increased (HR: 1.16/5% increase, p = 0.017). All
      relationships remained significant after multivariate analysis. The extent of
      fibrosis and nonsustained ventricular tachycardia were univariate predictors for
      arrhythmic end points (sustained ventricular tachycardia or ventricular
      fibrillation, appropriate implantable cardioverter-defibrillator discharge,
      sudden cardiac death) (HR: 1.30, p = 0.014). Nonsustained ventricular tachycardia
      remained an independent predictor of arrhythmic end points after multivariate
      analysis, but the extent of fibrosis did not. CONCLUSIONS: In patients with HCM,
      myocardial fibrosis as measured by late gadolinium enhancement cardiovascular
      magnetic resonance is an independent predictor of adverse outcome. (The
      Prognostic Significance of Fibrosis Detection in Cardiomyopathy; NCT00930735).

PMID- 20688033
TI  - Long-term outcome after drug-eluting versus bare-metal stent implantation in
      patients with ST-segment elevation myocardial infarction: 3-year follow-up of the
      randomized DEDICATION (Drug Elution and Distal Protection in Acute Myocardial
      Infarction) Trial.
AB  - OBJECTIVES: The purpose of this study was to compare long-term clinical outcomes
      after implantation of drug-eluting stents (DES) and bare-metal stents (BMS) in
      patients with ST-segment elevation myocardial infarction (STEMI). BACKGROUND: The
      evidence of long-term efficacy and safety after implantation of DES in patients
      with complex lesions is scarce. METHODS: We randomly assigned 626 patients with
      STEMI referred within 12 h to have a DES or a BMS implanted in the infarct
      related lesion with or without distal protection during primary percutaneous
      coronary intervention. RESULTS: At 3 years, target lesion revascularization was
      6.1% in the DES group compared with 16.3% in the BMS group (p<0.001), and the
      rate of major adverse cardiac events was 11.5% versus 18.2%, respectively
      (p=0.02). Whereas all-cause mortality did not differ significantly, the rate of
      cardiac death was higher in the DES group, 6.1% versus 1.9% for the BMS group
      (p=0.01). The occurrence of reinfarction, stroke, and stent thrombosis was
      similar. CONCLUSIONS: Implantation of DES in patients with STEMI reduces the long
      term rate of major adverse cardiac events compared with BMS, but patients with
      DES had a higher risk of cardiac death not attributed to myocardial infarction or
      stent thrombosis. (Drug Elution and Distal Protection During Percutaneous
      Coronary Intervention in ST Elevation Myocardial Infarction [DEDICATION];
      NCT00192868)

PMID- 20688034
TI  - Pediatric measles vaccine expressing a dengue tetravalent antigen elicits
      neutralizing antibodies against all four dengue viruses.
AB  - Dengue disease is an increasing global health problem that threatens one-third of
      the world's population. To control this emerging arbovirus, an efficient
      preventive vaccine is still needed. Because four serotypes of dengue virus (DV)
      coexist and antibody-dependent enhanced infection may occur, most strategies
      developed so far rely on the administration of tetravalent formulations of four
      live attenuated or chimeric viruses. Here, we evaluated a new strategy based on
      the expression of a single minimal tetravalent DV antigen by a single replicating
      viral vector derived from pediatric live-attenuated measles vaccine (MV). We
      generated a recombinant MV vector expressing a DV construct composed of the four
      envelope domain III (EDIII) from the four DV serotypes fused with the ectodomain
      of the membrane protein (ectoM). After two injections in mice susceptible to MV
      infection, the recombinant vector induced neutralizing antibodies against the
      four serotypes of dengue virus. When immunized mice were further inoculated with
      live DV from each serotype, a strong memory neutralizing response was raised
      against all four serotypes. A combined measles-dengue vaccine might be attractive
      to immunize infants against both diseases where they co-exist.

PMID- 20688035
TI  - Development of novel lipidated analogs of picroside as vaccine adjuvants:
      acylated analogs of picroside-II elicit strong Th1 and Th2 response to ovalbumin
      in mice.
AB  - The acylated analogs of picroside-II were synthesized and tested for immune
      adjuvant activity in the presence of weak antigen ovalbumin found to stimulate
      anti-OVA IgG titer, neutralizing antibody (IgG1 and IgG2a) titer as well as the
      production of soluble mediators of a Th1 response (IL-2 and IFN-gamma) and Th2
      response (IL-4) and proliferation of T lymphocytes sub-sets (CD4/CD8).
      Furthermore, these modified analogs of picroside-II were able to elicit a
      substantial increase in anti-OVA IgG when compared with OVA alone. These results
      support the use of acylated analogs particularly PK-II-3 and PK-II-4 as potent
      enhancer of antigen-specific Th1 and Th2 immune responses and thus are promising
      immune-adjuvant candidate for vaccines.

PMID- 20688036
TI  - High-throughput automated image analysis of neuroinflammation and
      neurodegeneration enables quantitative assessment of virus neurovirulence.
AB  - Historically, the safety of live attenuated vaccine candidates against
      neurotropic viruses was assessed by semi-quantitative analysis of virus-induced
      histopathology in the central nervous system of monkeys. We have developed a high
      throughput automated image analysis (AIA) for the quantitative assessment of
      virus-induced neuroinflammation and neurodegeneration. Evaluation of the results
      generated by AIA showed that quantitative estimates of lymphocytic infiltration,
      microglial activation, and neurodegeneration strongly and significantly
      correlated with results of traditional histopathological scoring. In addition, we
      show that AIA is a targeted, objective, accurate, and time-efficient approach
      that provides reliable differentiation of virus neurovirulence. As such, it may
      become a useful tool in establishing consistent analytical standards across
      research and development laboratories and regulatory agencies, and may improve
      the safety evaluation of live virus vaccines. The implementation of this high
      throughput AIA will markedly advance many fields of research including virology,
      neuroinflammation, neuroscience, and vaccinology.

PMID- 20688037
TI  - Heterosubtypic immunity to influenza mediated by liposome adjuvanted H5N1
      recombinant protein vaccines.
AB  - A non-egg, non-culture based influenza vaccine that intervenes large influenza
      outbreaks and protects against heterosubtypic infections is needed. Candidates of
      such vaccine are likely to be conserved influenza virus proteins or their coding
      DNA. The vaccine must be conveniently produced at reasonable cost, safe, highly
      immunogenic and should be able to recall rapidly the immunological memory upon
      the antigenic re-exposure. In this study vaccines made of full length recombinant
      NP and M2 of the H5N1 influenza A virus were entrapped either alone or together
      into liposome (L) made of phosphatidylcholine and cholesterol. The vaccines (L
      NP, L-M2 or L-NP+M2) and mocks (L or PBS) were safe without causing any adverse
      reaction in the intramuscularly injected mice. They were readily immunogenic at a
      single dose and a recalled response could be detected within one day post
      booster. Cytokine and antibody data indicated that the vaccines induced a Th1
      bias immune response. NP containing vaccines stimulated a marked increase of
      cytotoxic lymphocytes, i.e., CD8(+), intracellular IFNgamma(+) cells, while M2
      containing vaccines elicited good antibody response which neutralized infectivity
      of heterologous influenza viruses. Although the three vaccines elicited different
      immunological defense factors; nevertheless, they similarly and readily abrogated
      lung histopathology mediated by viruses belonging to different H5N1
      clade/subclade and heterosubtypes including swine H1N1 and human H1N1/2009
      viruses. They protected the vaccinated mice against lethal challenges with mouse
      adapted avian H5N1 virus. The liposome adjuvanted vaccines which demonstrated
      high protective efficacy in mice warrant testing further in a non-rodent model as
      well as in humans.

PMID- 20688038
TI  - Seasonal influenza vaccine supply and target vaccinated population in China, 2004
      2009.
AB  - To better understand the gap between limited influenza vaccine supply and the
      target population for vaccination in China, we conducted a retrospective survey
      to quantify the production capacity, supply and sale of seasonal trivalent
      inactive vaccine (TIV) from the 2004-2005 through the 2008-2009 season, and
      estimated the target population who should receive annual influenza vaccine. The
      maximum domestic capacity to produce TIV was 126 million doses in 2009. A total
      of 32.5 million doses of TIV were supplied in 2008-2009, with an average annual
      increase rate of 18% from 16.9 million in 2004-2005. This represents an amount
      sufficient to vaccinate 1.9% of Chinese population. The average number of doses
      of TIV for sale by province ranged from <5 to 108 per 1000 people. The
      differences are explained in part by level of economic development but also
      influenced by local reimbursement policies in some provinces. Based on national
      recommendations, we estimated a target population of 570.6 million or 43% of the
      total population. Supply and domestic production capacity for influenza vaccine
      is currently insufficient to vaccinate the estimated target population in China.
      The Government of China should consider measures to improve domestic production
      capacity of influenza vaccine, expand successful promotional campaigns, and add
      cost subsidies in high risk groups to further encourage influenza vaccine usage.

PMID- 20688039
TI  - Low measles seropositivity rate among children and young adults: a sero
      epidemiological study in southern China in 2008.
AB  - To obtain sero-epidemiological profile and develop optimal strategies to promote
      measles elimination, we conducted a measles seroprevalence study using stratified
      sampling method in Guangzhou, southern China in 2008. 4036 samples were analyzed
      by the enzyme-linked immunosorbent assay method and the overall sero-positive
      rate of measles antibody was 70.6% (95% CI 69.2-72.0%). Positive seroprevalences
      differed among age groups (P=0.000) and a W-curve distribution was observed. The
      15-29 years group had the low positive rate of 58.8% (95% CI 54.9-62.7%). Catch
      up vaccination campaigns should be promoted among susceptible population of <= 29
      year olds including women of childbearing age.

PMID- 20688040
TI  - A clinical trial to evaluate the safety and immunogenicity of the LEISH-F1+MPL-SE
      vaccine when used in combination with meglumine antimoniate for the treatment of
      cutaneous leishmaniasis.
AB  - Forty-four adult patients with cutaneous leishmaniasis (CL) were enrolled in a
      randomized, double-blind, controlled, dose-escalating clinical trial and were
      randomly assigned to receive three injections of either the LEISH-F1+MPL-SE
      vaccine (consisting of 5, 10, or 20 MUg recombinant Leishmania polyprotein LEISH
      F1 antigen+25 MUg MPL-SE adjuvant) (n=27), adjuvant alone (n=8), or saline
      placebo (n=9). The study injections were given subcutaneously on Days 0, 28, and
      56, and the patients were followed through Day 336 for safety, immunological, and
      clinical evolution endpoints. All patients received chemotherapy with meglumine
      antimoniate starting on Day 0. The vaccine was safe and well tolerated. Nearly
      all vaccine recipients and no adjuvant-alone or placebo recipients demonstrated
      an IgG antibody response to LEISH-F1 at Day 84. Also at Day 84, 80% of vaccine
      recipients were clinically cured, compared to 50% and 38% of adjuvant-alone and
      placebo recipients. The LEISH-F1+MPL-SE vaccine was safe and immunogenic in CL
      patients and appeared to shorten their time to cure when used in combination with
      meglumine antimoniate chemotherapy.

PMID- 20688041
TI  - Control of hepatitis A by universal vaccination of children and adolescents: an
      achieved goal or a deferred appointment?
AB  - Temporal trends of Hepatitis A cases and vaccination coverage data against
      Hepatitis A Virus have been investigated to analyse the impact of the universal
      routine vaccination strategy more than 10 years from its introduction in Puglia
      (region of Southern Italy). The basic reproductive number (R(0)) before
      vaccination introduction and the effective reproductive number (R(e)) after
      introduction have been calculated. A progressive decrease in incidence has been
      recorded in Puglia during last 10 years. Vaccination coverage is actually 64.8%
      (95% CI: 52.7-76.9%) for children aged 12-24 months and of 67.6% (95% CI: 58.4
      76.8%) for 12-year-old adolescents. R(0) estimated in 1996 was 2.01; actually
      R(e) is 0.651. Theoretical age at infection is 31.82 years. Universal routine
      vaccination aimed at the control of direct transmission remains the milestone in
      the strategy for the containment of the disease in settings at an intermediate
      level of endemicity.

PMID- 20688043
TI  - The regulation of carotenoid pigmentation in flowers.
AB  - Carotenoids fulfill many processes that are essential for normal growth and
      development in plants, but they are also responsible for the breathtaking variety
      of red-to-yellow colors we see in flowers and fruits. Although such visual
      diversity helps to attract pollinators and encourages herbivores to distribute
      seeds, humans also benefit from the aesthetic properties of flowers and an entire
      floriculture industry has developed on the basis that new and attractive
      varieties can be produced. Over the last decade, much has been learned about the
      impact of carotenoid metabolism on flower color development and the molecular
      basis of flower color. A number of different regulatory mechanisms have been
      described ranging from the transcriptional regulation of genes involved in
      carotenoid synthesis to the control of carotenoid storage in sink organs. This
      means we can now explain many of the natural colorful varieties we see around us
      and also engineer plants to produce flowers with novel and exciting varieties
      that are not provided by nature.

PMID- 20688042
TI  - Long lived protection against pneumonic tularemia is correlated with cellular
      immunity in peripheral, not pulmonary, organs.
AB  - Protection against the intracellular bacterium Francisella tularensis within
      weeks of vaccination is thought to involve both cellular and humoral immune
      responses. However, the relative roles for cellular and humoral immunity in long
      lived protection against virulent F. tularensis are not well established. Here,
      we dissected the correlates of immunity to pulmonary infection with virulent F.
      tularensis strain SchuS4 in mice challenged 30 and 90 days after subcutaneous
      vaccination with LVS. Regardless of the time of challenge, LVS vaccination
      protected approximately 90% of SchuS4 infected animals. Surprisingly, control of
      bacterial replication in the lung during the first 7 days of infection was not
      required for survival of SchuS4 infection in vaccinated mice. Control and
      survival of virulent F. tularensis strain SchuS4 infection within 30 days of
      vaccination was associated with high titers of SchuS4 agglutinating antibodies,
      and IFN-gamma production by multiple cell types in both the lung and spleen. In
      contrast, survival of SchuS4 infection 90 days after vaccination was correlated
      only with IFN-gamma producing splenocytes and activated T cells in the spleen.
      Together these data demonstrate that functional agglutinating antibodies and
      strong mucosal immunity are correlated with early control of pulmonary infections
      with virulent F. tularensis. However, early mucosal immunity may not be required
      to survive F. tularensis infection. Instead, survival of SchuS4 infection at
      extended time points after immunization was only associated with production of
      IFN-gamma and activation of T cells in peripheral organs.

PMID- 20688044
TI  - The HPV-16 E5 protein represses expression of stress pathway genes XBP-1 and COX
      2 in genital keratinocytes.
AB  - The HPV-16 E5 protein resides in membranes of the endoplasmic reticulum (ER) and
      modulates cell growth and viral replication. In order to help define its
      biological activities, we analyzed E5-induced changes in human keratinocyte gene
      expression. Our studies identified the downregulation of spliced XBP-1
      transcripts, a key player in the ER stress response, as a biochemical marker of
      E5 expression. IRE1alpha, the endoribonuclease responsible for XBP-1 RNA
      splicing, was also downregulated. Furthermore, cDNA microarray analysis revealed
      the repression of COX-2, another member of the ER stress pathway. In contrast,
      these genes were not altered either by the low-risk HPV-6b E5, or a C-terminal
      HPV-16 E5 mutant, in which the histidine and alanine residues (conserved in high
      risk HPVs) were replaced with tyrosine and isoleucine (conserved in low-risk
      HPVs). HPV-16 E5 was also able to lower COX-2 mRNA levels in cells co-expressing
      E6/E7, suggesting that it might exert similar activity during viral replication.
      Interestingly, the E6/E7 genes were independently able to lower COX-2 transcripts
      compared to vector cells, indicating that multiple pathways of COX-2 repression
      exist. COX-2 downregulation by E5 could be overcome by thapsigargin or
      tunicamycin treatments, which initiate ER stress via calcium fluxes and abnormal
      protein glycosylation respectively, making it unlikely that E5 specifically
      tempers these pathways. Overall, our data indicate that E5 represses the cellular
      ER stress response and suggest a potential role for E5 during productive HPV
      infection.

PMID- 20688045
TI  - Heat shock augments angiotensin II-induced vascular contraction through increased
      production of reactive oxygen species.
AB  - A temporal increase in temperature triggers a series of stress responses and
      alters vascular smooth muscle (VSM) contraction induced by agonist stimulation.
      Here we examined the role of reactive oxygen species (ROS) in heat shock
      dependent augmentation of angiotensin II (AngII)-induced VSM contraction.
      Endothelium-denuded rat aortic rings were treated with heat shock for 45 min at
      42 degrees C and then subjected to assays for the production of force, ROS, and
      the expression of ROS-related enzymes. AngII-induced contraction was enhanced in
      heat shock-treated aorta. AngII-induced production of hydrogen peroxide and
      superoxide were elevated in response to the heat shock treatment. Pre-treatment
      with superoxide dismutases (SOD) mimetic and inhibitors for glutathione
      peroxidase and NADPH oxidase but not for xanthine oxidase eliminated an increase
      in the AngII-induced contraction in the heat shock-treated aorta. Heat shock
      increased the expression of p47phox, a cytosolic subunit of NADPH oxidase, but
      not Cu-Zn-SOD and Mn-SOD. In addition, heat shock increased contraction that was
      evoked by hydrogen peroxide and pyrogallol. These results suggest that heat shock
      causes an elevation of ROS as well as a sensitization of ROS signal resulting in
      an augmentation of VSM contraction in response to agonist.

PMID- 20688046
TI  - Dimethylcelecoxib inhibits mPGES-1 promoter activity by influencing EGR1 and NF
      kappaB.
AB  - DMC (dimethylcelecoxib={4-[5-(2,5-dimethylphenyl)-3(trifluoromethyl)-1H-pyrazol-1
      yl]benzenesulfonamide}) is a close derivative of celecoxib, without
      cyclooxygenase inhibiting properties up to very high concentrations.
      Nevertheless, after stimulation of various human cell lines with IL
      1beta/TNFalpha and simultaneous treatment with DMC PGE(2) synthesis is inhibited
      [1]. Here we investigated the effect of DMC on mPGES-1 promoter activity, using a
      reporter gene assay. Our data demonstrate that DMC inhibits mPGES-1 promoter
      activity by blocking nuclear EGR1 expression and repressing NF-kappaB
      transcriptional activity. Other putative transcription factors, known to regulate
      mPGES-1 expression, such as SP1 or CREB are not affected by DMC. Over-expression
      of EGR1 completely prevents the inhibitory effect of DMC on mPGES-1 promoter
      activity, indicating that the repressing effect of DMC on mPGES-1 expression is
      mainly dependent on blocking EGR1 expression. mPGES-1, EGR1 and NF-kappaB are
      important proteins involved in many pathological conditions such as inflammation
      and cancer. Therefore, DMC seems to be a promising substance to treat
      inflammatory and carcinogenic processes, although it does not inhibit
      cyclooxygenases.

PMID- 20688047
TI  - Nature or nurture: let food be your epigenetic medicine in chronic inflammatory
      disorders.
AB  - Numerous clinical, physiopathological and epidemiological studies have underlined
      the detrimental or beneficial role of nutritional factors in complex inflammation
      related disorders such as allergy, asthma, obesity, type 2 diabetes,
      cardiovascular disease, rheumatoid arthritis and cancer. Today, nutritional
      research has shifted from alleviating nutrient deficiencies to chronic disease
      prevention. It is known that lifestyle, environmental conditions and nutritional
      compounds influence gene expression. Gene expression states are set by
      transcriptional activators and repressors and are often locked in by cell
      heritable chromatin states. Only recently, it has been observed that the
      environmental conditions and daily diet can affect transgenerational gene
      expression via "reversible" heritable epigenetic mechanisms. Epigenetic changes
      in DNA methylation patterns at CpG sites (epimutations) or corrupt chromatin
      states of key inflammatory genes and noncoding RNAs, recently emerged as major
      governing factors in cancer, chronic inflammatory and metabolic disorders.
      Reciprocally, inflammation, metabolic stress and diet composition can also change
      activities of the epigenetic machinery and indirectly or directly change
      chromatin marks. This has recently launched re-exploration of anti-inflammatory
      bioactive food components for characterization of their effects on epigenome
      modifying enzymatic activities (acetylation, methylation, phosphorylation,
      ribosylation, oxidation, ubiquitination, sumoylation). This may allow to improve
      healthy aging by reversing disease prone epimutations involved in chronic
      inflammatory and metabolic disorders.

PMID- 20688048
TI  - Newly synthetic ceramide-1-phosphate analogs; their uptake, intracellular
      localization, and roles as an inhibitor of cytosolic phospholipase A(2)alpha and
      inducer of cell toxicity.
AB  - Ceramide-1-phosphate (C1P) regulates cellular functions including arachidonic
      acid (AA) metabolism and modulates cell fate. The mechanism by which C1P is taken
      up is unclear, and the development of lipophilic analogs may be useful for
      regulating C1P's actions. We synthesized new mono- and di-methyl-ester (MM and
      DM, respectively) analogs of C1P with N-acyl chains of different lengths, and
      examined their effects on AA release and cell toxicity. Short-N-acyl-DM-C1P
      analogs including C5- and C6-DM-C1P, but not long-N-acyl-DM-C1P analogs,
      inhibited the release of AA mediated by alpha type cytosolic phospholipase A(2)
      (cPLA(2)alpha) in Chinese hamster ovary (CHO) cells and the enzymatic activity.
      Short-N-acyl-DM-C1P analogs including C6-DM-C1P caused morphological changes with
      cell toxicity 24h after the treatment in three cells lines (CHO, L929, and RLC-18
      cells), although the role of AA in the toxicity was not clear. Neither long-N
      acyl-DM-C1P analogs nor MM-C1P analogs including C6-MM-C1P affected cPLA(2)alpha
      activity and cell toxicity. Similar to C6-ceramide having a 4-nitrobenzo-2-oxa
      1,3-diazole (NBD) group on a C6-N-acyl chain (NBD-C6-ceramide), NBD-C6-DM-C1P and
      C6-DM-C1P-NBD (with a C6-N-acyl chain and an NBD-labeled C14-alkyl chain) were
      accumulated in the Golgi complex, although less C6-DM-C1P-NBD than NBD-C6-DM-C1P
      was taken up. NBD-C6-ceramide was converted to various metabolites including NBD
      C6-sphingomyelin, but both NBD-C6-DM-C1P and C6-DM-C1P-NBD were stable in cells
      within 2h. The short-N-acyl-DM-C1P analogs acted directly as an inhibitor of
      cPLA(2)alpha and an inducer of cell toxicity, and may be useful for the
      regulation of ceramide/C1P-regulated responses.

PMID- 20688049
TI  - Comparison of the pharmacological properties of human and rat histamine H(3)
      receptors.
AB  - Ligand pharmacology of histamine H(3)-receptors is species-dependent. In previous
      studies, two amino acids in transmembrane domain 3 (TM III) were shown to play a
      significant role. In this study, we characterized human and rat histamine H(3)
      receptors (hH(3)R and rH(3)R, respectively), co-expressed with mammalian G
      proteins in Sf9 insect cell membranes. We compared a series of imidazole
      containing H(3)R ligands in radioligand binding and steady-state GTPase assays.
      H(3)Rs similarly coupled to Galpha(i/o)-proteins. Affinities and potencies of the
      agonists histamine, N(alpha)-methylhistamine and R-(alpha)-methylhistamine were
      in the same range. Imetit was only a partial agonist. The pharmacology of imetit
      and proxifan was similar at both species. However, impentamine was more potent
      and efficacious at rH(3)R. The inverse agonists ciproxifan and thioperamide
      showed higher potency but lower efficacy at rH(3)R. Clobenpropit was not species
      selective. Strikingly, imoproxifan was almost full agonist at hH(3)R, but an
      inverse agonist at rH(3)R. Imoproxifan was docked into the binding pocket of
      inactive and active hH(3)R- and rH(3)R-models and molecular dynamic simulations
      were performed. Imoproxifan bound to hH(3)R and rH(3)R in E-configuration, which
      represents the trans-isomer of the oxime-moiety as determined in crystallization
      studies, and stabilized active hH(3)R-, but inactive rH(3)R-conformations. Large
      differences in electrostatic surfaces between TM III and TM V cause differential
      orientation of the oxime-moiety of imoproxifan, which then differently interacts
      with the rotamer toggle switch Trp(6.48) in TM VI. Collectively, the substantial
      species differences at H(3)Rs are explained at a molecular level by the use of
      novel H(3)R active-state models.

PMID- 20688050
TI  - Modulation of cell sensitivity to antitumor agents by targeting survival
      pathways.
AB  - The advent of drugs targeting tumor-associated prosurvival alterations of cancer
      cells has changed the interest of antitumor drug development from cytotoxic drugs
      to target-specific agents. Although single-agent therapy with molecularly
      targeted agents has shown limited success in tumor growth control, a promising
      strategy is represented by the development of rational combinations of target
      specific agents and conventional antitumor drugs. Activation of
      survival/antiapoptotic pathways is a common feature of cancer cells that converge
      in the development of cellular resistance to cytotoxic agents. The survival
      pathways implicated in cellular response to drug treatment are primarily PI3K/Akt
      and Ras/MAPK, which also mediate the signalling activated by growth factors and
      play a role in the regulation of critical processes including cell proliferation,
      metabolism, apoptosis and angiogenesis. Inhibitors of PI3K, Akt and mTOR have
      been shown to sensitize selected tumor cells to cytotoxic drugs through multiple
      downstream effects. Moreover, the MAPK pathway, also implicated in the regulation
      of gene expression in response to stress stimuli, can interfere with the
      chemotherapy-induced proapoptotic signals. Targeting Hsp90, which acts as a
      molecular chaperone for survival factors including Akt, may have the potential
      advantage to simultaneously block multiple oncogenic pathways. Overall, the
      available evidence supports the interest of rationally designed approaches to
      enhance the efficacy of conventional antitumor treatments through the inhibition
      of survival pathways and the notion that the concomitant targeting of multiple
      pathways may be a successful strategy to deal with tumor heterogeneity and to
      overcome drug resistance of tumor cells.

PMID- 20688051
TI  - Comparison of low-density lipoprotein cholesterol concentrations measured by a
      direct homogeneous assay and by the Friedewald formula in a large community
      population.
AB  - BACKGROUND: We compare the direct homogeneous low-density lipoprotein cholesterol
      (LDL-C) assay with the Friedewald formula (FF) for determination of LDL-C in a
      large community-dwelling population. METHODS: A total of 21,194 apparently
      healthy subjects aged 40 to 79 years with triglyceride (TG) concentrations <4.52
      mmol/l were enrolled. LDL-C were directly measured by the enzymatic homogeneous
      assay (LDL-C (D)) and also estimated by the FF (LDL-C (F)). Paired t-test,
      Pearson's correlation coefficient and linear regression analysis were performed
      and the concordances of the National Cholesterol Education Program (NCEP) risk
      category were estimated. RESULTS: Both in fasting (n=3270) and nonfasting samples
      (n=17,924), LDL-C (D) highly correlated with LDL-C (F): r=0.971 and 0.955,
      respectively. Concordant results for NCEP categories were 84.8% for fasting
      samples and 80.1% for nonfasting samples. However, the bias between the 2
      measurements increased in samples with TG concentrations >1.69 mmol/l, especially
      in nonfasting samples. CONCLUSIONS: The results showing less variability of the
      direct LDL-C assay than that of the FF in nonfasting samples suggest that
      epidemiological studies can use LDL-C measured by the direct assay both in
      fasting and nonfasting samples.

PMID- 20688052
TI  - Biological variability of glycated hemoglobin.
AB  - BACKGROUND: The measurement of glycated hemoglobin (HbA(1c)) has a pivotal role
      in monitoring glycemic state in diabetic patients. Furthermore, the American
      Diabetes Association has recently recommended the use of HbA(1c) for diabetes
      diagnosis, but a clear definition of the clinically allowable measurement error
      is still lacking. Information on biological variability of the analyte can be
      used to achieve this goal. METHODS: We systematically reviewed the published
      studies on the biological variation of HbA(1c) to check consistency of available
      data in order to accurately define analytical goals. RESULTS: The nine recruited
      studies were limited by choice of analytic methodology, population selection,
      protocol application and statistical analyses. CONCLUSIONS: There is an urgent
      need to determine biological variability of HbA(1c) using a specific and
      traceable assay, appropriate protocol and appropriate statistical evaluation of
      data.

PMID- 20688053
TI  - Cell-free DNA in the blood as a solid tumor biomarker--a critical appraisal of
      the literature.
AB  - Circulating cell-free DNA (cfDNA) has been suggested as a cancer biomarker.
      Several studies assessed the usefulness of quantitative and qualitative tumor
      specific alterations of cfDNA, such as DNA strand integrity, frequency of
      mutations, abnormalities of microsatellites, and methylation of genes, as
      diagnostic, prognostic, and monitoring markers in cancer patients. Most of the
      papers that could be evaluated in this review resulted in a positive conclusion.
      However, methodical diversity without the traceability of data and differently
      designed and often underpowered studies resulted in divergent results between
      studies. In addition, the limited diagnostic sensitivity and specificity of cfDNA
      alterations temper the effusive hope of novel tumor markers, raising similar
      issues as those for other tumor markers. To validate the actual clinical validity
      of various cfDNA alterations as potential cancer biomarkers in practice for
      individual tumor types, the main problems of the observed uncertainties must be
      considered in future studies. These include methodical harmonization concerning
      sample collection, processing, and analysis with the traceability of measurement
      results as well as the realization of well-designed prospective studies based on
      power analysis and sample size calculations.

PMID- 20688054
TI  - Serum adipocyte fatty acid binding proteins and adiponectin in patients with
      coronary artery disease: the significance of A-FABP/adiponectin ratio.
AB  - BACKGROUND: Adipocyte fatty acid binding protein (A-FABP) and adiponectin have
      been shown to play important roles in atherosclerosis. We investigated serum A
      FABP, adiponectin and A-FABP/adiponectin ratio in patients with coronary artery
      disease (CAD). METHODS: A total of 340 subjects who underwent coronary
      angiography (CAG) were classified into CAD group (n=211) and non-CAD group
      (n=129) according to the CAG. Serum A-FABP and adiponectin concentrations were
      determined by enzyme-linked immunosorbent assays. RESULTS: CAD patients tend to
      have higher A-FABP concentrations than non-CAD subjects, the difference is
      significant only between female CAD patients and controls [22.8 (18.6-25.7) ng/ml
      vs 18.1 (15.6-21.8) ng/ml, P=0.008]. Serum A-FABP concentration was independently
      associated with Gensini scores in female subjects (P=0.018). CAD patients have
      significant higher serum A-FABP/adiponectin ratio [1.51 +/- 0.05 vs 0.89 +/- 0.03
      ng/MUg, P<0.01] than controls in both genders. CONCLUSIONS: Serum A-FABP is
      associated with CAD more closely in female than in male. The A-FABP/adiponectin
      ratio may be a more useful indicator for CAD than A-FABP or adiponectin alone.

PMID- 20688055
TI  - Subcellular localization of leukotriene receptors in human endothelial cells.
AB  - Leukotriene B(4) (LTB(4)), a potent chemotactic and immune-modulating mediator,
      signals via two receptors, BLT(1) and BLT(2). Recently, we reported that BLT(1)
      is the predominating BLT expressed on human umbilical vein endothelial cells
      (HUVEC), and that BLT(1) mediated functions are enhanced by LTB(4) and
      lipopolysaccharide (LPS), but not by TNFalpha. Here, we demonstrate that BLT(1)
      is found on the outer cell membrane of HUVECs but also in intracellular granules,
      co-localized with monocyte chemotactic protein-1 and P-selectin, but not with
      interleukin-8 and von Willebrand factor. Upon stimulation with LTB(4) or LPS,
      more BLT(1) protein is found, now evenly distributed over the cytoplasm and in
      the cell nucleus, but less on the cell surface. An MAP kinase inhibitor prevented
      this enhancement and translocation, suggesting this signaling pathway to be
      crucial. Thus, BLT(1), a G-protein-coupled 7-transmembrane receptor, is located
      in various subcellular compartments in endothelial cells, which may have
      implications for cellular LT dependent responses and target accessibility for
      BLT(1) antagonists.

PMID- 20688056
TI  - Increased cellular apoptosis susceptibility (CSE1L/CAS) protein expression
      promotes protrusion extension and enhances migration of MCF-7 breast cancer
      cells.
AB  - Microtubules are part of cell structures that play a role in regulating the
      migration of cancer cells. The cellular apoptosis susceptibility (CSE1L/CAS)
      protein is a microtubule-associated protein that is highly expressed in cancer.
      We report here that CSE1L regulates the association of alpha-tubulin with beta
      tubulin and promotes the migration of MCF-7 breast cancer cells. CSE1L was
      associated with alpha-tubulin and beta-tubulin in GST (glutathione S-transferase)
      pull-down and immunoprecipitation assays. CSE1L-GFP (green fluorescence protein)
      fusion protein experiments showed that the N-terminal of CSE1L interacted with
      microtubules. Increased CSE1L expression resulted in decreased tyrosine
      phosphorylation of alpha-tubulin and beta-tubulin, increased alpha-tubulin and
      beta-tubulin association, and enhanced assembly of microtubules. Cell protrusions
      or pseudopodia are temporary extensions of the plasma membrane and are implicated
      in cancer cell migration and invasion. Increased CSE1L expression increased the
      extension of MCF-7 cell protrusions. In vitro migration assay showed that
      enhanced CSE1L expression increased the migration of MCF-7 cells. Our results
      indicate that CSE1L plays a role in regulating the extension of cell protrusions
      and promotes the migration of cancer cells.

PMID- 20688057
TI  - Dynamin-like protein 1 at the Golgi complex: a novel component of the
      sorting/targeting machinery en route to the plasma membrane.
AB  - The final step in the liberation of secretory vesicles from the trans-Golgi
      network (TGN) involves the mechanical action of the large GTPase dynamin as well
      as conserved dynamin-independent fission mechanisms, e.g. mediated by Brefeldin A
      dependent ADP-ribosylated substrate (BARS). Another member of the dynamin family
      is the mammalian dynamin-like protein 1 (DLP1/Drp1) that is known to constrict
      and tubulate membranes, and to divide mitochondria and peroxisomes. Here, we
      examined a potential role for DLP1 at the Golgi complex. DLP1 localized to the
      Golgi complex in some but not all cell lines tested, thus explaining
      controversial reports on its cellular distribution. After silencing of DLP1, an
      accumulation of the apical reporter protein YFP-GL-GPI, but not the basolateral
      reporter VSVG-SP-GFP at the Golgi complex was observed. A reduction in the
      transport of YFP-GL-GPI to the plasma membrane was confirmed by surface
      immunoprecipitation and TGN-exit assays. In contrast, YFP-GL-GPI trafficking was
      not disturbed in cells silenced for BARS, which is involved in basolateral
      sorting and trafficking of VSVG-SP-GFP in COS-7 cells. Our data indicate a new
      role for DLP1 at the Golgi complex and thus a role for DLP1 as a novel component
      of the apical sorting machinery at the TGN is discussed.

PMID- 20688058
TI  - Plasmodium falciparum: differential merozoite dose requirements for maximal
      production of various inflammatory cytokines.
AB  - The ligand specificity of TLRs and the details of signaling pathways that are
      activated by ligand-receptor engagements have been studied extensively. However,
      it is not known whether the signaling events initiated by defined doses of ligand
      are uniformly effective in producing various cytokines. In this study, we
      investigated the dose requirement for the saturated production of representative
      inflammatory cytokines, TNF-alpha, IL-6 and IL-12, by DCs stimulated with
      Plasmodium falciparum merozoites/protein-DNA complex or a CpG ODN TLR9 ligand.
      The data demonstrate that the ligand doses required for the maximal expression of
      TNF-alpha and IL-6 are substantially higher than those required for the maximal
      production of IL-12. The data also demonstrate that the uptake capacity of
      malaria parasite by plasmacytoid DCs is markedly lower than that of myeloid DCs,
      and that, like myeloid DCs, plasmacytoid DCs produce significant levels of TNF
      alpha and IL-12 when the uptake of malarial DNA is facilitated by carrier
      molecules such as polylysine or cationic lipids. These results have implications
      for enhancing the effectiveness of vaccine against malaria by modulating the
      innate immune responses of plasmacytoid DCs to malaria parasites.

PMID- 20688059
TI  - Vaccination of chickens with DNA vaccine encoding Eimeria acervulina 3-1E and
      chicken IL-15 offers protection against homologous challenge.
AB  - Eimeria acervulina 3-1E antigen gene and mature chicken interleukin 15 (mChIL-15)
      gene were cloned into expression vector pcDNA3.1(+) in different forms, produced
      DNA vaccine pcDNA3.1-3-1E, and pcDNA3.1-3-1E-linker-mChIL-15 co-expressing E.
      acervulina 3-1E gene and mChIL-15 gene, respectively. The expression of objective
      gene in vitro was detected by indirect fluorescent antibody technique and
      immunohistochemistry. The two DNA vaccines were administered by intramuscular leg
      injection. An animal challenge experiment was carried out to evaluate the immune
      protective efficacy of the vaccines. The results indicated that DNA vaccines were
      successfully constructed and the expression of objective gene could be detected
      in vitro. The animal experimental results showed that both DNA vaccines could
      provide partial protection against homologous challenge in chickens. The chimeric
      DNA vaccine, pcDNA3.1-3-1E-linker-mChIL-15, could significantly increase oocyst
      decrease ratio, reduce the average lesion score in the duodenum, improve body
      weight gain, and increase anti-coccidial index (ACI) compared to the DNA vaccine
      pcDNA3.1-3-1E. Taken together, these results demonstrate ChIL-15 enhance the
      immunogenicity of 3-1E DNA vaccine, and co-expression of cytokine and optimized
      surface antigen of Eimeria may be a promising method to enhance immunogenicity of
      DNA vaccines in poultry.

PMID- 20688060
TI  - Changes in plasma hormone levels correlate with fledging in nestling Leach's
      storm-petrels.
AB  - Leach's storm-petrels accumulate large amounts of body mass throughout the
      nestling period. Approximately 4days before fledging, nestlings weigh 50-100%
      more than adults. In order to shed this excess mass, nestlings engage in
      behavioral anorexia, and leave the burrow when they are light enough to fly.
      During this prefledging period, we measured several plasma hormones
      (corticosterone, thyroxine, and testosterone) to determine whether the behavioral
      changes associated with fledging are correlated with endocrine changes. In
      several species, including petrels, corticosterone levels are known to increase
      near fledging. Reduced food consumption has been shown to elevate corticosterone
      levels and decrease thyroxine levels in nestling birds. In nestling storm
      petrels, levels of both corticosterone and thyroxine increased. Storm-petrels
      were found to secrete measurable levels of testosterone, but levels did not
      change during the prefledging period. Increased corticosterone levels might be
      part of an endocrine signal that initiates changes in feeding behavior, or may
      result from reduced food intake. Elevated thyroxine levels may be related to
      metabolic changes involved in mass loss. Future experimental work is needed to
      ascertain whether the described endocrine changes are responsible for, or result
      from, prefledging changes in petrel feeding behavior.

PMID- 20688061
TI  - Stress and the timing of breeding: glucocorticoid-luteinizing hormones
      relationships in an arctic seabird.
AB  - In birds, stressful environmental conditions delay the timing of breeding but the
      underlying mechanisms are poorly understood. The stress hormone corticosterone
      appears to be a good candidate for mediating the decision to breed and when to
      start egg-laying, via a possible inhibition of luteinizing hormone (LH) and sex
      steroids production. We used luteinizing hormone releasing hormone (LHRH)
      challenge in pre-laying male and female Black-legged kittiwakes (Rissa
      tridactyla) to test whether LH and testosterone secretion were depressed by
      elevated corticosterone levels. Females bearing high baseline corticosterone
      levels showed reduced baseline LH levels and a low ability to release LH,
      following LHRH challenge. Further, females bearing low baseline LH levels and
      elevated baseline corticosterone levels were more likely to skip breeding.
      However, non-breeding females were physiologically primed for breeding, since
      they mounted high LHRH-induced LH release. Egg-laying date was advanced in good
      body condition females but was unaffected by hormones secretion. In males,
      corticosterone levels had no effect on LH and/or testosterone secretion and did
      not affect their decision to breed. Interestingly, males with high LHRH-induced
      testosterone release bred early. Our study highlights clear sex-differences in
      the HPG sensitivity to stress hormones in pre-laying kittiwakes. Because females
      have to store body reserves and to build up the clutch, they would be more
      sensitive to stress than males. Moreover, intrasexual competition could force
      male kittiwakes to acquire reproductive readiness earlier in the season than
      females and to better resist environmental perturbations. We suggest that high
      testosterone releasing ability would mediate behavioural adjustments such as
      courtship feeding, which would stimulate early egg-laying in females.

PMID- 20688062
TI  - Progesterone and reproduction in marsupials: a review.
AB  - Progesterone (P4) profiles throughout pregnancy and the oestrous cycle are
      reviewed in a wide range of marsupial species, representing 12 Families, and
      focus on the corpus luteum (CL) and its functioning, compared with its eutherian
      counterpart. Physiologically, P4 subtends the same fundamental processes
      supporting gestation in marsupials as it does in eutherian mammals, from its role
      in stimulating the secretory endometrium, effecting nutritional transfer across
      the placenta and establishing lactogenesis. Before the formation of the CL,
      however, secretion of P4 is widespread throughout many Families and the dual
      roles of P4 in the induction of sexual behaviour and ovulation are exposed. In
      Dasyuridae, raised levels of P4 are linked with the induction of sexual
      receptivity and are also present around the time of mating in Burramyidae,
      Petauridae and Tarsipedidae, but their function is unknown. Only in Didelphidae
      has research established that the pheromonally-induced levels of pro-oestrous P4
      trigger ovulation. This is principally the role of oestradiol in the eutherian
      and may be an important difference between the marsupial and the eutherian. The
      deposition of the shell coat around the early marsupial embryo is also a function
      of P4, but perhaps the most striking difference is seen in the time taken to form
      the CL. This is not always immediate and the maximum secretion of P4 from the
      granulosa cells may not occur until some 2 weeks after ovulation. The slower
      development of the CL in some species is linked with delays in the development of
      the embryo during its unattached phase and results in relatively long gestation
      periods. A common feature of these, in monovular species, is a short pulse of P4
      from the newly-luteinised CL, which is all that is needed for the subsequent
      development of the embryo to term. Maternal recognition of pregnancy occurs soon
      after the formation of the blastocyst, with embryo-induced changes in ovarian
      production of P4 and the uterine endometrium. The embryo, similar to the
      eutherian, determines the length of the gestation period and initiates its own
      birth, but in direct contrast, the embryo of some marsupial species shortens the
      life-span of the CL. The evidence points to a different strategy; one of a
      reduction, rather than an expansion of the potential ovarian and placental
      support available during pregnancy. The marsupial mode of reproduction, where all
      species produce highly altricial young, receiving complex and extensive maternal
      care, has facilitated the adaptive radiation of this group and avoided the need
      for precociality.

PMID- 20688063
TI  - Social status regulates kisspeptin receptor mRNA in the brain of Astatotilapia
      burtoni.
AB  - The brain controls reproduction in response to relevant external and internal
      cues. Central to this process in vertebrates is gonadotropin-releasing hormone
      (GnRH1) produced in neurons of the hypothalamic-preoptic area (POA). GnRH1
      released from the POA stimulates pituitary release of gonadotropins, which in
      males causes sperm production and concomitant steroid hormone release from the
      testes. Kisspeptin, a neuropeptide acting via the kisspeptin receptor (Kiss1r),
      increases GnRH1 release and is linked to development of the reproductive system
      in mammals and other vertebrates. In both fish and mammals, kiss1r mRNA levels
      increase in the brain around the time of puberty but the environmental and other
      stimuli regulating kisspeptin signaling to GnRH1 neurons remain unknown. To
      understand where kiss1r is expressed and how it is regulated in the brain of a
      cichlid fish, Astatotilapia burtoni, we measured expression of a kiss1r homolog
      mRNA by in situ hybridization and quantitative reverse transcription-PCR (qRT
      PCR). We found kiss1r mRNA localized in the olfactory bulb, specific nuclei in
      the telencephalon, diencephalon, mesencephalon, and rhombencephalon, as well as
      in GnRH1 and GnRH3 neurons. Since males' sexual physiology and behavior depend on
      social status in A. burtoni, we also tested how status influenced kiss1r mRNA
      levels. We found higher kiss1r mRNA levels in whole brains of high status
      territorial males and lower levels in low status non-territorial males. Our
      results are consistent with the hypothesis that Kiss1r regulates many functions
      in the brain, making it a strong candidate for mediating differences in
      reproductive physiology between territorial and non-territorial phenotypes.

PMID- 20688064
TI  - The endocrinology of stress in fish: an environmental perspective.
AB  - Much of the understanding of the endocrine basis of stress in fish comes from
      studies of cultured stocks of teleosts; there is comparatively little information
      on stress responses in wild stock, and less still on chondrosteans and
      elasmobranchs. This understanding is being refined through increasing
      understanding of molecular processes underlying endocrine events, with molecular
      tools offering ready examination of parts of the endocrine pathway that have been
      resistant to easy measurement of hormone products. An assessment of the
      timecourse of activation of the hypothalamic-pituitary-interrenal axis shows
      generally strong independence of temperature, with most teleosts showing
      measurable increase in plasma cortisol within 10 min of stress. Chondrostean and
      elasmobranch responses are less well described, but in chondrosteans at least,
      the response pattern appears to be similar to teleosts. The short latency for
      increases in corticosteroids following exposure to a stressor means that sampling
      of wild fish needs to occur rapidly after encounter. Several techniques including
      underwater sampling and rapid line capture are suitable for this, as is
      measurement of steroid release to the water by undisturbed fish, albeit possibly
      with a reduced range of applications. Basal cortisol values in wild teleosts are
      typically <10 ng mL(-1), but a number of species show values orders of magnitude
      higher in unstressed fish. Variability in corticosteroid levels arises from a
      range of factors in addition to stress including, sex and maturity, time of day
      or since feeding, and season. These factors need to be understood for the
      sensible assessment of stress responses in wild fish. Studies on free-living
      birds suggest that environmental stress resides mainly around unpredictable
      change, and the limited data available for fish support this view. The effect of
      unpredictable event such as floods or storms are difficult to assess in wild fish
      due to the difficulty in sampling at these times, and would be predicted to
      impose environmental stress as in terrestrial systems; however, this has yet to
      be demonstrated. There is scope for use of stress responses to be used as a
      measure of environmental quality but only if the basic response to environmental
      stress is well understood first. Development of this understanding remains a
      priority for this field of research.

PMID- 20688065
TI  - Maternal care effects on the development of a sexually dimorphic motor system:
      the role of spinal oxytocin.
AB  - Maternal licking in rats affects the development of the spinal nucleus of the
      bulbocavernosus (SNB), a sexually dimorphic motor nucleus that controls penile
      reflexes involved with copulation. Reduced maternal licking results in decreased
      motoneuron number, size, and dendritic length in the adult SNB, as well as
      deficits in adult male copulatory behavior. Our previous findings that licking
      like tactile stimulation influences SNB dendritic development and upregulates Fos
      expression in the lumbosacral spinal cord suggest that afferent signaling is
      changed by differences in maternal stimulation. Oxytocin afferents from the
      hypothalamus are a possible candidate, given previous research that has shown
      oxytocin is released following sensory stimulation, oxytocin modulates
      excitability in the spinal cord, and is a pro-erectile modulator of male sex
      behavior. In this experiment, we used immunofluorescence and immediate early gene
      analysis to assess whether licking-like tactile stimulation of the perineum
      activated parvocellular oxytocinergic neurons in the hypothalamus in neonates. We
      also used enzyme immunoassay to determine whether this same stroking stimulation
      produced an increase in spinal oxytocin levels. We found that stroking increased
      Fos immunolabeling in small oxytocin-positive cells in the paraventricular
      nucleus of the hypothalamus, in comparison to unstroked or handled control pups.
      In addition, 60s of licking-like perineal stimulation produced a transient 89%
      increase in oxytocin levels in the lumbosacral spinal cord. Together, these
      results suggest that oxytocin afferent activity may contribute to the effects of
      early maternal care on the masculinization of the SNB and resultant male
      copulatory behavior.

PMID- 20688067
TI  - Stress, social behaviour, and secondary sexual traits in a male primate.
AB  - We examined variation in glucocorticoid levels in the mandrill, a brightly
      coloured primate species, to identify major social influences on stress hormones,
      and investigate relationships among glucocorticoid levels, testosterone and
      secondary sexual ornamentation. We collected a total of 317 fecal samples for 16
      adult male mandrills over 13 months, including mating and non-mating periods and
      periods of both dominance rank stability and instability, and compared fecal
      glucocorticoid levels with dominance rank, rank stability, presence of receptive
      females, gastro-intestinal parasite infection, fecal testosterone and facial red
      coloration. Glucocorticoid levels did not vary systematically with dominance
      rank, but increased when the dominance hierarchy was unstable, and increased in
      the presence of receptive females. The relationship between dominance rank and
      glucocorticoid levels changed direction according to the stability of the
      dominance hierarchy: glucocorticoid levels were higher in subordinate males under
      stable conditions, but under conditions of instability higher ranking males had
      higher glucocorticoid levels. The influence of dominance rank also interacted
      with the presence of receptive females: glucocorticoids were higher in dominant
      males than in subordinates, but only during mating periods, suggesting that
      dominant males are more stressed than subordinates during such periods. These
      findings support previous studies showing that the relationship between
      glucocorticoids and dominance rank in male baboons is dependent on the social
      environment. We also found that males with higher glucocorticoids suffered a
      higher diversity of gastrointestinal parasite infection, in line with evidence
      that glucocorticoids suppress the immune system in other species. However, we
      found no support for the stress-mediated immunocompetence handicap hypothesis for
      the evolution of condition-dependent ornaments: glucocorticoid and testosterone
      levels were positively related, rather than the negative relationship predicted
      by the hypothesis, and we found no relationship between red colour and
      glucocorticoid levels, suggesting that glucocorticoids do not play a role in
      translating social conditions or physical health into ornament expression in this
      species.

PMID- 20688066
TI  - Corticotrophin-releasing factor mediates hypophagia after adrenalectomy,
      increasing meal-related satiety responses.
AB  - Adrenalectomy-induced hypophagia is associated with increased satiety-related
      responses, which involve neuronal activation of the nucleus of the solitary tract
      (NTS). Besides its effects on the pituitary-adrenal axis, corticotrophin
      releasing factor (CRF) has been shown to play an important role in feeding
      behaviour, as it possesses anorexigenic effects. We evaluated feeding-induced CRF
      mRNA expression in the paraventricular nucleus (PVN) and the effects of
      pretreatment with CRF(2) receptor antagonist (Antisauvagine-30, AS30) on food
      intake and activation of NTS neurons in response to feeding in adrenalectomised
      (ADX) rats. Compared to the sham group, ADX increased CRF mRNA levels in the PVN
      of fasted animals, which was further augmented by refeeding. AS30 treatment did
      not affect food intake in the sham and ADX+corticosterone (B) groups; however, it
      reversed hypophagia in the ADX group. In vehicle-pretreated animals, refeeding
      increased the number of Fos and Fos/TH-immunoreactive neurons in the NTS in the
      sham, ADX and ADX+B groups, with the highest number of neurons in the ADX
      animals. Similarly to its effect on food intake, pretreatment with AS30 in the
      ADX group also reversed the increased activation of NTS neurons induced by
      refeeding while having no effect in the sham and ADX+B animals. The present
      results show that adrenalectomy induces an increase in CRF mRNA expression in the
      PVN potentiated by feeding and that CRF(2) receptor antagonist abolishes the
      anorexigenic effect and the increased activation of NTS induced by feeding in the
      ADX animals. These data indicate that increased activity of PVN CRF neurons
      modulates brainstem satiety-related responses, contributing to hypophagia after
      adrenalectomy.

PMID- 20688068
TI  - Estradiol does not influence strategy choice but place strategy choice is
      associated with increased cell proliferation in the hippocampus of female rats.
AB  - Adult neurogenesis occurs in the hippocampus of most mammals. While the function
      of adult hippocampal neurogenesis is not known, there is a relationship between
      neurogenesis and hippocampus-dependent learning and memory. Ovarian hormones can
      influence learning and memory and strategy choice. In competitive memory tasks,
      higher levels of estradiol shift female rats towards the use of the place
      strategy. Previous studies using a cue-competition paradigm find that 36% of male
      rats will use a hippocampus-dependent place strategy and place strategy users had
      lower levels of cell proliferation in the hippocampus. Here, we used the same
      paradigm to test whether endogenous or exogenous ovarian hormones influence
      strategy choice in the cue-competition paradigm and whether cell proliferation
      was related to strategy choice. We tested ovariectomized estradiol-treated (10
      microg of estradiol benzoate) or sham-operated female rats on alternating blocks
      of hippocampus-dependent and hippocampus-independent versions of the Morris water
      task. Rats were then given a probe session with the platform visible and in a
      novel location. Preferred strategy was classified as place strategy (hippocampus
      dependent) if they swam to the old platform location or cue strategy (hippocampus
      independent) if they swam to the visible platform. All groups showed a preference
      for the cue strategy. However, proestrous rats were more likely to be place
      strategy users than rats not in proestrus. Female place strategy users had
      increased cell proliferation in the dentate gyrus compared to cue strategy users.
      Our study suggests that 78% of female rats chose the cue strategy instead of the
      place strategy. In summary the present results suggest that estradiol does not
      shift strategy use in this paradigm and that cell proliferation is related to
      strategy use with greater cell proliferation seen in place strategy users in
      female rats.

PMID- 20688069
TI  - Relevance of mating-associated stimuli, ovulation, and the progesterone receptor
      for the post-coital inhibition of estrous behavior in the female rabbit.
AB  - Estrous female domestic rabbits (Oryctolagus cuniculus) display scent marking
      ("chinning") and sexual receptivity. Mating induces ovulation, which occurs
      approximately 12h later, and also decreases chinning and receptivity. In the
      present study, we explored the participation of mating-associated stimuli,
      ovulation, and the progesterone receptor (PR) in mediating such behavioral
      effects. We found that copulatory stimuli were not necessary, and that ovulation
      alone was sufficient, as these behavioral changes were replicated in unmated
      females by intravenous administration of human chorionic gonadotropin (hCG). The
      post-mating administration (s.c.) of 5MUg/day estradiol benzoate (EB), prevented
      the decline in chinning and receptivity. A lower dose of EB (1MUg/day) had no
      effect, nor did the antiprogestin RU486 (20mg, s.c., administered 3h before
      mating). However, the combination of a single pre-mating administration of RU486
      plus the post-mating administration of 1MUg/day EB completely blocked the decline
      in estrous behavior. We propose that PR activation around the time of mating and
      a post-mating decline in ovarian estradiol secretion and/or estradiol
      responsiveness act in parallel to terminate estrus in this species.

PMID- 20688070
TI  - Chronic corticosterone during pregnancy and postpartum affects maternal care,
      cell proliferation and depressive-like behavior in the dam.
AB  - Stress during pregnancy and the postpartum can influence the well-being of both
      the mother and her offspring. Prolonged elevated levels of glucocorticoids are
      associated with depression and we developed an animal model of postpartum
      depression/stress based on high levels of corticosterone (CORT) during the
      postpartum. Gestational stress is a risk factor for postpartum depression and
      prenatal and/or postnatal high levels of CORT may have differential effects on
      the mother. Thus the present study was conducted to investigate the effects of
      low (10mg/kg) or high levels of CORT (40mg/kg) given to dams either during
      gestation, postpartum or across both gestation and postpartum on maternal care,
      depressive-like behavior and hippocampal cell proliferation in the dam. Only the
      high dose of CORT administered during the postpartum increased depressive-like
      behavior in the dam. Furthermore the high dose of CORT altered maternal care
      (reduced time spent on the nest and nursing) regardless of whether administration
      of CORT was during gestation or postpartum. Gestational and/or postpartum
      treatment with high CORT and postpartum low CORT reduced cell proliferation in
      the dentate gyrus of postpartum dams compared to oil-treated controls. Thus
      prolonged treatment with high levels of CORT postpartum reduced maternal care,
      hippocampal cell proliferation and induced depressive-like behavior in the dam
      and therefore might be considered an animal model of postpartum depression. More
      research is needed to understand the effects of stress hormones during different
      phases of reproduction and how they affect the brain and behavior of the mother
      and her offspring.

PMID- 20688071
TI  - Brain androgen receptor expression correlates with seasonal changes in the
      behavior of a weakly electric fish, Brachyhypopomus gauderio.
AB  - Seasonal breeders are superb models for understanding natural relationships
      between reproductive behavior and its neural bases. We investigated the cellular
      bases of hormone effects in a weakly pulse-type electric fish with well-defined
      hormone-sensitive communication signals. Brachyhypopomus gauderio males emit
      social electric signals (SESs) consisting of rate modulations of the electric
      organ discharge during the breeding season. This discharge is commanded by a
      medullary pacemaker nucleus (PN), composed of pacemaker and relay neurons. We
      analyzed the contribution of androgen receptor (AR) expression to the seasonal
      generation of SESs, by examining the presence of ARs in the PN in different
      experimental groups: breeding, non-breeding, and testosterone (T)-implanted non
      breeding males. AR presence and distribution in the CNS was assessed through
      western blotting and immunohistochemistry using the PG-21 antibody, which was
      raised against the human AR. We found AR immunoreactivity, for the first time in
      a pulse-type Gymnotiform, in several regions throughout the brain. In particular,
      this is the first report to reveal the presence of AR in both pacemaker and relay
      neurons within the Gymnotiform PN. The AR immunoreactivity was present in
      breeding males and could be induced in T-implanted non-breeding males. This
      seasonal and T-induced AR expression in the PN suggests that androgens may play
      an important role in the generation of SESs by modulating intrinsic
      electrophysiological properties of pacemaker and relay neurons.

PMID- 20688072
TI  - Improved detection of cell surface proteins using an electrochemiluminescent cell
      binding assay.
AB  - Cell surface protein profiling is a generic tool to determine the quality of
      cultured mammalian cell lines. Flow cytometry is commonly employed as the
      screening technique of choice, but it consumes a large quantity of cells. We have
      evaluated an electrochemiluminescent (ECL)-based platform, the Meso Scale
      Discovery (MSD) Sector 6000 Imager, for cell surface protein detection with fewer
      than 100 cells per well. The detection of CD13 on human foreskin fibroblast (HFF)
      cells was evaluated using indirect detection of the reverse-phase immunoassays in
      96-well and 384-well plate formats. The study has shown robust cell surface
      detection of CD13 on HFF cells using the 384-well plate format, with a LOD of
      15.3 +/- 6.5 cells (n=3). The 96-well plate format exhibited far greater
      variability between experiments, such that the best LOD obtained was 42.5 cells
      per well. We have demonstrated, with our model system, the feasibility to perform
      cell-binding assays with as few as 15 cells per well of a 384-well microplate
      using the MSD platform.

PMID- 20688073
TI  - Identification of helper T cell master regulator candidates using the polar score
      method.
AB  - The T helper paradigm is currently being revised from the Th1-Th2 dichotomy to a
      multi-state paradigm involving a number of different cell phenotypes.
      Transcriptional profiling using microarrays has been used to study the
      development of these phenotypes. There is however no clear consensus on how to
      approach the analysis of this data, especially in the context of cells that are
      triggered to expand rapidly, and massively change their gene expression pattern.
      We develop a method we call 'polar score' to identify genes that are related to T
      helper cell polarization. This method is designed to identify polarizing genes in
      a set where many genes change expression. To illustrate the use of this
      technique, we apply it to published T cell microarray data and compare it to
      conventional analysis methods. With the new method, we find evidence for the
      existence of IL9 producing T cells ('Th9 cells') that are induced by a
      combination of TGFbeta and IL4. We identify several candidate master regulator
      genes for this phenotype. Furthermore, treatment with TGFbeta and IL12 results in
      a Treg and Th17 hybrid cell phenotype.

PMID- 20688074
TI  - Surgically increased ovarian mass in the honey bee confirms link between
      reproductive physiology and worker behavior.
AB  - Honey bee (Apis mellifera L.) workers are essentially sterile females that are
      used to study how complex social behavior develops. Workers perform nest tasks,
      like nursing larvae, prior to field tasks, like foraging. Despite worker
      sterility, this behavioral progression correlates with ovary size: workers with
      larger ovaries (many ovary filaments) start foraging at younger ages on average.
      It is untested, however, whether the correlation confers a causal relationship
      between ovary size and behavioral development. Here, we successfully grafted
      supernumerary ovaries into worker bees to produce an artificial increase in the
      amount of ovary tissue. We next measured fat body mRNA levels for the yolk
      precursor gene vitellogenin, which influences honey bee behavioral development
      and can correlate with ovary size. Vitellogenin was equally expressed in surgical
      controls and bees with supernumerary ovaries, leading us to predict that these
      groups would be characterized by equal behavior. Contrary to our prediction, bees
      with supernumerary ovaries showed accelerated behavioral development compared to
      surgical controls, which behaved like reference bees that were not treated
      surgically. To explore this result we monitored fat body expression levels of a
      putative ecdysteroid-response gene, HR46, which is genetically linked to ovary
      size in workers. Our data establish that social insect worker behavior can be
      directly influenced by ovaries, and that HR46 expression changes with ovary size
      independent of vitellogenin.

PMID- 20688075
TI  - Diet-specific salivary gene expression and glucose oxidase activity in Spodoptera
      exigua (Lepidoptera: Noctuidae) larvae.
AB  - Saliva secreted during caterpillar feeding contains enzymes to initiate digestion
      or detoxify noxious plant compounds. Activity of some salivary enzymes is diet
      dependent and may be transcriptionally regulated. In this study, cDNA-amplified
      fragment length polymorphism was used to identify beet armyworm, Spodoptera
      exigua Hubner, labial salivary genes that are differentially expressed in
      response to diet. In addition, SeGOX was sequenced based on homology and
      characterized to confirm that the transcript encodes a functional enzyme. Three
      labial salivary transcripts, encoding glucose oxidase (GOX) and two proteins of
      unknown function (Se1H and Se2J), were expressed in a diet-specific manner. Since
      diet, particularly the protein to digestible carbohydrate levels and ratio, may
      affect labial salivary enzyme activity, the influence of nutritional quality on
      gene expression was determined. Transcript levels of the labial salivary genes
      Se1H, Se2J and SeGOX increased with dietary carbohydrate levels, regardless of
      protein concentrations. In contrast GOX enzymatic activity increased with
      increasing dietary carbohydrates when caterpillars were fed protein-rich diets,
      but not when caterpillars were fed protein-poor diets. Our results suggest that
      dietary carbohydrates affect SeGOX, Se1H and Se2J transcription, but dietary
      protein or amino acid levels affect translational and/or post-translational
      regulation of the enzyme GOX.

PMID- 20688076
TI  - Total body nitrogen and total body carbon as indicators of body protein and body
      lipids in the melon fly Bactrocera cucurbitae: effects of methoprene, a juvenile
      hormone analogue, and of diet supplementation with hydrolyzed yeast.
AB  - The application of methoprene, and providing access to diet including hydrolyzed
      yeast, are treatments known to enhance mating success in the male melon fly
      Bactrocera cucurbitae Coquillett (Diptera: Tephritidae), supporting their use in
      mass rearing protocols for sterile males in the context of sterile insect
      technique (SIT) programmes. The objective of the present laboratory study was to
      investigate the effect of methoprene application and diet supplementation with
      hydrolyzed yeast (protein) on the turnover of body lipids and protein to confirm
      the feasibility of their application in melon fly SIT mass-rearing programmes.
      While females had access to a diet that included hydrolyzed yeast (protein),
      males were exposed to one of the following treatments: (1) topical application of
      methoprene and access to diet including protein (M+P+); (2) only diet including
      protein (M-P+); (3) only methoprene (M+P-) and (4) untreated, only sugar-fed,
      control males (M-P-). Total body carbon (TBC) and total body nitrogen (TBN) of
      flies were measured at regular intervals from emergence to 35 days of age for
      each of the different treatments. Nitrogen assimilation and turnover in the flies
      were measured using stable isotope ((15)N) dilution techniques. Hydrolyzed yeast
      incorporation into the diet significantly increased male body weight, TBC and TBN
      as compared to sugar-fed males. Females had significantly higher body weight, TBC
      and TBN as compared to all males. TBC and TBN showed age-dependent changes,
      increasing until the age of sexual maturity and decreasing afterwards in both
      sexes. Methoprene treatment did not significantly affect TBC or TBN. The
      progressive increase with age of TBC suggests that lipogenesis occurs in adult
      male B. cucurbitae, as is the case in other tephritids. Stable isotope dilution
      was shown to be an effective method for determining N uptake in B. cucurbitae.
      This technique was used to show that sugar-fed males rely solely on larval N
      reserves and that the N uptake rate in males with access to diet including
      hydrolyzed yeast was higher shortly after emergence and then stabilized. The
      implications of the results for SIT applications are discussed.

PMID- 20688077
TI  - Phylogenetic position of Octosporea muscaedomesticae (Microsporidia) and its
      relationship to Octosporea bayeri based on small subunit rDNA analysis.
AB  - Comparative phylogenetic analysis of the small subunit rDNA sequence of
      Octosporea muscaedomesticae (Flu, 1911) (type species) (Microsporidia) isolated
      from the blowfly Phormia regina (Diptera:Calliphoridae) is presented. Neighbor
      Joining bootstrap, Maximum Parsimony and Maximum Likelihood analyses with 38
      microsporidian taxa representing five major clades of Microsporidia placed O.
      muscaedomesticae on a separate branch within a clade containing parasites of
      freshwater hosts. O. muscaedomesticae differed from Octosporea bayeri, a parasite
      of the microcrustacean, Daphnia magna (Cladocera:Daphniidae) by 29% demonstrating
      that the latter microsporidium is not closely related to the type species at the
      generic level, and should not be placed within the genus Octosporea, a conclusion
      that is further supported by morphological and developmental differences.
      Considering the number of disparately related hosts from which Octosporea species
      have been previously described based mostly on developmental and morphological
      characters it is likely that many will not fit the current definition of the
      genus, and it is possible that molecular analysis of these species will show that
      this genus as defined represents a polyphyletic grouping of unrelated taxa.

PMID- 20688078
TI  - Qo site of mitochondrial complex III is the source of increased superoxide after
      transient exposure to hydrogen peroxide.
AB  - Transient exposure of cardiac myocytes to hydrogen peroxide (H(2)O(2)) results in
      further production of superoxide by the mitochondria as a result of increased
      influx of calcium through the L-type Ca(2+) channel and increased calcium uptake
      by the mitochondria. The response persists as a result of positive feedback on
      the channel and induces alterations in protein synthesis and cell size consistent
      with the development of myocyte hypertrophy. The aim of this study was to
      investigate the site of increased superoxide production within the mitochondria.
      Exposure of myocytes to 30 MUM H(2)O(2) (5 min) then 10 U/mL catalase (5 min)
      increased dihydroethidium (DHE) signal by 58.7 +/- 12.0% (n=4) compared to
      myocytes exposed to 0 MUM H(2)O(2) for 5 min followed by 10 U/mL catalase (n=9).
      Complex I inhibitors DPI (n=5) and rotenone (n=7) attenuated the increase in DHE
      signal due to H(2)O(2). Complex III inhibitors myxothiazol (n=16) and
      stigmatellin (n=5) also attenuated the increase in DHE signal due to H(2)O(2).
      However, antimycin A (inhibitor of Q(i) site of complex III) had no effect. We
      "isolated" complex III in the intact cell by applying succinate in the patch
      pipette and exposing the cell to rotenone and antimycin A. Myxothiazol and TCA
      cycle inhibitors alpha-keto-beta-methyl-n-valeric acid (KMV) and 4-hydroxynonenal
      (4-HNE) completely attenuated the increase in DHE signal. Direct activation of
      the L-type Ca(2+) channel by voltage-step mimicked the increase in DHE signal
      after transient exposure to H(2)O(2) (47.6 +/- 17.8%, n=6) while intracellular
      application of catalase attenuated the increase in DHE signal due to H(2)O(2)
      (n=6). We propose that elevated superoxide production after transient exposure to
      H(2)O(2) occurs at the Q(o) superoxide generation site of complex III in cardiac
      myocytes and that an increase in TCA cycle activity plays a significant role in
      mediating the response.

PMID- 20688079
TI  - Chloroplast import signals: the length requirement for translocation in vitro and
      in vivo.
AB  - Protein translocation of cytosolically synthesized proteins requires signals for
      both targeting of precursor proteins to the surface of the respective compartment
      and their transfer across its membrane. In contrast to signals for peroxisomal
      and endoplasmic reticulum translocation, the signals for mitochondrial and
      chloroplast transport are less well defined with respect to length and amino acid
      requirements. To study the properties of signals required for translocation into
      chloroplasts in vitro and in vivo, we used fusion proteins composed of transit
      peptides and the Ig-like module of the muscle protein titin as passenger. We
      observed that about 60 amino acids-longer than the transit peptide length of many
      experimentally confirmed chloroplast proteins-are required for efficient
      translocation. However, within native chloroplast precursor proteins with transit
      peptides shorter than 60 amino acids, extension appears to be present as they are
      efficiently imported into organelles. In addition, the interaction of an unfolded
      polypeptide stretch of 60 or more amino acids with receptors at the chloroplast
      surface results in the unidirectionality of protein translocation into
      chloroplasts even in the presence of a competing C-terminal peroxisomal targeting
      signal. These findings prove the existing ideas that initial targeting is defined
      by the N-terminal signal and that the C-terminal signal is sensed only
      subsequently.

PMID- 20688080
TI  - Considerations for using integral feedback control to construct a perfectly
      adapting synthetic gene network.
AB  - It has long been known to control theorists and engineers that integral feedback
      control leads to, and is necessary for, "perfect" adaptation to step input
      perturbations in most systems. Consequently, implementation of this robust
      control strategy in a synthetic gene network is an attractive prospect. However,
      the nature of genetic regulatory networks (density-dependent kinetics and
      molecular signals that easily reach saturation) implies that the design and
      construction of such a device is not straightforward. In this study, we propose a
      generic two-promoter genetic regulatory network for the purpose of exhibiting
      perfect adaptation; our treatment highlights the challenges inherent in the
      implementation of a genetic integral controller. We also present a numerical case
      study for a specific realization of this two-promoter network, "constructed"
      using commonly available parts from the bacterium Escherichia coli. We illustrate
      the possibility of optimizing this network's transient response via analogy to a
      linear, free-damped harmonic oscillator. Finally, we discuss extensions of this
      two-promoter network to a proportional-integral controller and to a three
      promoter network capable of perfect adaptation under conditions where first-order
      protein removal effects would otherwise disrupt the adaptation.

PMID- 20688081
TI  - A stochastic model of neuronal growth cone guidance regulated by multiple
      sensors.
AB  - Neuronal growth cones migrate directionally under the control of axon guidance
      molecules, thereby forming synapses in the developing brain. The signal
      transduction system by which a growth cone detects surrounding guidance
      molecules, analyzes the detected signals, and then determines the overall
      behavior remains undetermined. In this study, we describe a novel stochastic
      model of this behavior that utilizes multiple sensors on filopodia to respond to
      guidance molecules. Overall growth cone behavior is determined by using only the
      concentration gradients of guidance molecules in the immediate vicinity of each
      sensor. The detected signal at each sensor, which is treated as a vector
      quantity, is sent to the growth cone center and then integrated to determine
      axonal growth in the next step by means of a simple vector operation. We compared
      the results of computer simulations of axonal growth with observations of actual
      axonal growth from co-culture experiments using olfactory bulb and septum. The
      probabilistic distributions of axonal growth generated by the computer simulation
      were consistent with those obtained from the culture experiments, indicating that
      our model accurately simulates growth cone behavior. We believe that this model
      will be useful for elucidating the as yet unknown mechanisms responsible for
      axonal growth in vivo.

PMID- 20688082
TI  - New method for comparing DNA primary sequences based on a discrimination measure.
AB  - We introduce a new approach to compare DNA primary sequences. The core of our
      method is a new measure of pairwise distances among sequences. Using the
      primitive discrimination substrings of sequence S and Q, a discrimination measure
      DM(S, Q) is defined for the similarity analysis of them. The proposed method does
      not require multiple alignments and is fully automatic. To illustrate its
      utility, we construct phylogenetic trees on two independent data sets. The
      results indicate that the method is efficient and powerful.

PMID- 20688083
TI  - The option to leave: conditional dissociation in the evolution of cooperation.
AB  - Conditional dissociation, i.e. the option to leave an interacting partner in
      response to his behaviour, is a mechanism that has been shown to promote
      cooperation in several settings, but the fundamental features that make
      conditional dissociation work in this way are not yet fully understood. This
      paper identifies some of the key conditions that make conditional dissociation
      lead to high levels of cooperation, explains how this mechanism can support the
      evolutionary coexistence of cooperative and non-cooperative behaviour typically
      observed in nature, and provides an analytical formula to estimate the expected
      degree of cooperation thus achieved. Our model involves a population of
      individuals who are paired to play an iterated prisoner's dilemma. All
      individuals share the same capacity to react to the action previously chosen by
      their partner and, without any other a priori constraint or exclusion, they may
      use any behavioural rule that is compatible with this capacity. The dynamic
      evolution of the population eventually enters either a non-cooperative or a
      partially cooperative regime, depending mainly on the expected lifetime of
      individuals. Whenever the partially cooperative regime materializes, the
      cornerstone of its long-run stability is the coexistence of defectors and "Out
      for-Tat" strategists, the latter being those who start cooperating and respond to
      defection by merely leaving. We find, therefore, that conditional dissociation is
      the essential disciplinary device supporting cooperation, whilst other
      conditional strategies (such as Tit-for-Tat) remain present only in small
      population shares. These conclusions are obtained both by extensive numerical
      simulations and through analytical mean-field methods that approximate the
      stochastic simulation dynamics and deliver accurate predictions for general
      parameter configurations.

PMID- 20688084
TI  - Defence, intrusion and the evolutionary stability of territoriality.
AB  - Territorial behaviour can only be adaptive if its costs are outweighed by its
      benefits. Territorial individuals incur costs by defending their territories
      against intruders. Usually these intruders are assumed to be non-territorial
      floaters attempting to take over the whole territory or neighbours trying to
      extend the borders of their own territory. We instead investigate how costs and
      benefits of territorial behaviour are affected by neighbours which invade to
      steal resources on a territory. We show analytically that in the absence of
      defence intrusion into neighbouring territories always pays and that even if
      territories are defended intrusion levels can still be high. Using a more
      detailed simulation model we find that territory defence usually disappears from
      the population even if owners have a strong advantage over intruders in terms of
      fighting costs or foraging efficiency. Defence and thus territoriality can only
      be evolutionarily stable if fighting costs for the intruder relative to the
      productivity of the territory are very high or if crossing the borders between
      territories carries additional costs. Our results show that stealing of resources
      by neighbours can have a considerable effect on the evolutionary stability of
      territory defence and thus territoriality itself. A more mechanistic model of
      territorial behaviour is needed to incorporate these kinds of mechanisms into a
      general theory on the evolution of territoriality.

PMID- 20688085
TI  - Cox-2 inhibition attenuates cardiovascular and inflammatory aspects in monosodium
      glutamate-induced obese rats.
AB  - AIMS: the purpose of the present work was to investigate the effect of
      cyclooxygenase-2 (COX-2) inhibition on the cardiovascular and inflammatory
      aspects promoted by monosodium glutamate (MSG)-induced obesity in rats. MAIN
      METHODS: Neonatal Wistar male rats were injected with MSG (4 mg/g body weight ID)
      or equimolar saline (control). Treatment with celecoxib (50 mg/kg ip) or saline
      (0.9% NaCl ip) began at 60 days of age. At 90 days, all rats were anesthetized
      for catheterization of the femoral artery, and the mean arterial pressure (MAP)
      and heart rate (HR) were recorded once consciousness was regained. KEY FINDINGS:
      MSG obese rats were hypertensive (MAP=138+/-4 mm Hg) compared with controls
      (MAP=118+/-2 mm Hg). After treatment with celecoxib, the hypertension was
      attenuated (MAP=126+/-2 mm Hg) in obese rats without changes in HR. The
      retroperitoneal and periepididymal fat weighed more in obese rats (Obese:
      Retro=7.08+/-0.51, Peri=6.36+/-0.81, CONTROL: Retro=3.60+/-0.46; Peri=3.24+/
      0.42), but celecoxib did not alter these parameters. Plasma nitric oxide levels
      were not different between groups. However, the level of plasma prostaglandins,
      the immunohistochemical staining of COX-2 in cardiac tissue and plasma
      lipoperoxidation were higher in obese rats, and celecoxib attenuated these
      parameters. MSG produced liver steatosis that was also attenuated following
      celecoxib treatment. SIGNIFICANCE: Our data demonstrate an association between
      increased blood pressure and products of COX-2 in obese rats, suggesting a role
      for prostaglandins in the hypertensive and inflammatory aspects of MSG-induced
      obesity.

PMID- 20688086
TI  - Vector representations and related matrices of DNA primary sequence based on L
      tuple.
AB  - We consider to construct 4(L)-components vectors for a DNA primary sequence based
      on the L-tuple. For two DNA sequences, using the corresponding vectors, we
      construct a set of L x L matrices called related matrix. The mathematical
      characterization from the constructed matrices have been selected to characterize
      the degree of similarity between the two DNA sequences. The search for similar
      sequences of a query sequence from a database of 39 library sequences and the
      construction of phylogenetic tree of H5N1 avian influenza virus illustrate the
      utility of the matrices for DNA sequences.

PMID- 20688087
TI  - fMRI studies of successful emotional memory encoding: A quantitative meta
      analysis.
AB  - Over the past decade, fMRI techniques have been increasingly used to interrogate
      the neural correlates of successful emotional memory encoding. These
      investigations have typically aimed to either characterize the contributions of
      the amygdala and medial temporal lobe (MTL) memory system, replicating results in
      animals, or delineate the neural correlates of specific behavioral phenomena. It
      has remained difficult, however, to synthesize these findings into a systems
      neuroscience account of how networks across the whole-brain support the enhancing
      effects of emotion on memory encoding. To this end, the present study employed a
      meta-analytic approach using activation likelihood estimates to assess the
      anatomical specificity and reliability of event-related fMRI activations related
      to successful memory encoding for emotional versus neutral information. The meta
      analysis revealed consistent clusters within bilateral amygdala, anterior
      hippocampus, anterior and posterior parahippocampal gyrus, the ventral visual
      stream, left lateral prefrontal cortex and right ventral parietal cortex. The
      results within the amygdala and MTL support a wealth of findings from the animal
      literature linking these regions to arousal-mediated memory effects. The
      consistency of findings in cortical targets, including the visual, prefrontal,
      and parietal cortices, underscores the importance of generating hypotheses
      regarding their participation in emotional memory formation. In particular, we
      propose that the amygdala interacts with these structures to promote enhancements
      in perceptual processing, semantic elaboration, and attention, which serve to
      benefit subsequent memory for emotional material. These findings may motivate
      future research on emotional modulation of widespread neural systems and the
      implications of this modulation for cognition.

PMID- 20688088
TI  - Early fitness consequences and hormonal correlates of parental behaviour in the
      social rodent, Octodon degus.
AB  - Males are expected to assist their mates whenever this behaviour raises survival
      of offspring with little expense in terms of mating opportunities. At a more
      proximate level, cortisol and testosterone hormones seem involved in the
      expression of parental care in mammals. We examined the consequences to postnatal
      offspring development and survival of the males' presence in the social rodent,
      Octodon degus. Offspring quality and quantity, and maternal condition of females
      were contrasted among females rearing their litters in the presence of the sire,
      females breeding in the presence of a non-breeding female, and females breeding
      solitarily. We related these differences to variation in parental behaviour and
      plasma levels of testosterone and cortisol. Twenty two females and their litters
      were studied under constant conditions of adult density, nest availability, food
      availability, and breeding experience. Males huddled over and groomed offspring.
      However, neither the number nor the mass of pups from dams that nested with the
      sire differed from those recorded to breeding females that nested with a non
      breeding female and females that nested solitarily. Body weight loss and
      associated levels of plasma cortisol in dams nesting with the sire were similar
      to those of solitary females, but higher than mothers nesting with a non-breeding
      female. Thus, male care had no consequences to offspring, and seemed detrimental
      to breeding females. Circulating levels of cortisol and total testosterone were
      either poor (mothers) or no (fathers, non-breeding females) predictors of
      parental care.

PMID- 20688089
TI  - Stress alters food intake and glucosensing response in hypothalamus, hindbrain,
      liver, and Brockmann bodies of rainbow trout.
AB  - In fish food intake is altered under stress conditions, and in a fish teleost
      model like rainbow trout food intake is associated with the activity of the
      glucosensor systems. Thus, we aimed to evaluate the possible interaction of
      stress with the response of glucosensor mechanisms in rainbow trout. Thus, we
      subjected rainbow trout (via intraperitoneal injections) to normoglycaemic
      (control), hypoglycaemic (4 mg.kg(-1) bovine insulin) or hyperglycaemic (500
      mg.kg(-1) glucose body mass) conditions for 5 days under normal stocking density
      (NSD, 10 kg fish mass.m(-3)) or stress conditions induced by high stocking
      density (HSD, 70 kg fish mass.m(-3)). The experimental design was appropriate
      since hypoglycemia and hyperglycemia were observed in fish under NSD whereas in
      normoglycaemic fish HSD induced changes in stress-related parameters similar to
      those reported in fish literature, such as increased levels of cortisol and
      glucose in plasma and decreased levels of glycogen in liver. Food intake did not
      respond to changes in plasma glucose levels in fish under HSD conditions, in
      contrast with the decreased food intake observed when glucose levels increased in
      fish under NSD conditions. Moreover, the changes with the increase in plasma
      glucose levels in parameters involved in glucosensing in liver, Brockmann bodies
      (BB), hypothalamus, and hindbrain of fish in NSD either disappeared (DHAP and GAP
      levels, and GK, PK, and GPase activities in liver; glucose, DHAP and GAP levels
      in BB; glucose and DHAP levels, and GK and PK activities in hypothalamus;
      glycogen and DHAP levels, and GSase activity in hindbrain) or changed (cortisol
      levels in plasma; glycogen and GAP levels, and GSase and FBPase activities in
      liver; GK and PK activities in BB; GK and PK activities in hindbrain) in fish
      under HSD. Those changes suggest for the first time in fish the existence of an
      interaction between glucosensing capacity and stress. The readjustment in the
      activity of glucosensor systems is also associated with changes in food intake
      resulting in an inability of the fish to compensate with changes in food intake
      those of circulating glucose levels as observed in fish under non-stressed
      conditions.

PMID- 20688090
TI  - Long-term physiological and behavioral effects of exposure to a highly palatable
      diet during the perinatal and post-weaning periods.
AB  - Environmental conditions promote weight gain in children and adults, with early
      nutritional states and the availability of energy condensed/high-fat palatable
      diets appearing to facilitate the development of obesity. Little is known about
      the extent to which prenatal and postnatal dietary manipulations alter the
      response of the adult offspring to high-fat, highly palatable diets. Here we
      exposed rat dams to highly palatable diet (supplemental diet, SD), rich in fat
      and sugars, during pregnancy and lactation, and assessed the potential
      interactions with the effects of a similar diet offered post-weaning on a range
      of physiological and behavioral parameters in the adult male offspring. Post
      weaning exposure to SD increased body weight, body fat, and plasma leptin levels,
      as well as the plasma glucose response to glucose challenge, compared to chow-fed
      rats. Combining perinatal SD with post-weaning exposure (SD/SD group) elevated
      fasting plasma glucose levels, and induced leptin resistance in the adult rats.
      The same treatment also resulted in sensitized locomotor response to an acute
      injection of amphetamine. The glucocorticoid response to stress was not affected
      by the dietary treatments. We conclude that exposure of mother and young to a
      highly palatable diet with high-fat and high sugar content during the critical
      perinatal period, increases the risk of developing an obesity-like condition in
      rats exposed to the same palatable diet post-weaning, and this effect may be
      accompanied by adaptations in the reward-related mesostriatal dopaminergic
      system.

PMID- 20688091
TI  - Role of caloric homeostasis and reward in alcohol intake in Syrian golden
      hamsters.
AB  - The Syrian golden hamster drinks alcohol readily, but only achieves moderate
      blood alcohol levels, and does not go through withdrawal from alcohol. Because
      the hamster is a model of caloric homeostasis, both caloric content and reward
      value may contribute to the hamster's alcohol consumption. The current study
      examines alcohol consumption in the hamster when a caloric or non-caloric sweet
      solution is concurrently available and caloric intake in the hamster before,
      during, and after exposure to either: alcohol, sucrose or saccharin. In
      Experiments 1 and 2, hamsters were given access to alcohol (15% v/v) and water;
      once alcohol consumption steadied, a bottle containing an ascending concentration
      of sucrose (99-614 mM) or saccharin (2-10 mM), or water was added. In Experiment
      3, hamsters were given access to alcohol (15% v/v), sucrose (614 mM), saccharin
      (4 mM), or a second water bottle for 14 days. After the second bottle was
      removed, measurements continued for 14days. Sucrose exposure suppressed alcohol
      consumption at concentrations lower in calories than the alcohol solution.
      Saccharin exposure failed to suppress alcohol consumption. Exposure to sucrose
      and alcohol but not saccharin decreased food intake. Decreased alcohol
      consumption in response to a caloric sweetener and decreased food intake during
      alcohol exposure support that alcohol consumption by the hamster is mediated by
      caloric content. However, suppression of alcohol intake by a sucrose solution of
      lower caloric content and the equivalent intake of individual alcohol, sucrose
      and saccharin solutions support a role for reward value in alcohol consumption.

PMID- 20688093
TI  - Testosterone treatment of pregnant rabbits affects sexual development of their
      daughters.
AB  - The intrauterine position (IUP) may affect the sexual development of a female
      fetus in litter-bearing mammals. Females gestating between two males (2M) develop
      into masculinized adults compared to females without contiguous males (0M).
      Fetuses are known to secrete different types and amounts of steroid hormones
      during the prenatal period, and diffusing steroids may affect sexual
      differentiation of their neighbors, too. Exposure of elevated testosterone (T)
      levels generally results in masculinized anatomy and behavior in females of
      several rodent species. Our recent study showed that IUP-dependent
      masculinization is also present in the domestic rabbit, which shows large
      variation in sex related traits as adults. The aim of the present study was to
      test if the IUP effect in rabbits can be induced by exogenous testosterone
      treatment. By administering different doses of testosterone propionate (TP) to
      pregnant rabbits, and following anatomical and behavioral development of their
      female offspring, we obtained dose-dependent increase both in the anogenital
      distance (AGD) and chin-marking behavior of prenatal T exposed females. The
      effects of treatment corresponded to the variation due to intrauterine position
      in our previous study, namely, exposure to T of known external origin resulted in
      similar tendencies of masculinization in rabbit females as the in utero proximity
      to male siblings. Our results suggest that the IUP effects may have similar
      physiological bases across different mammalian taxa including Lagomorphs.

PMID- 20688092
TI  - Delayed alternation performance in rats following recovery from early iron
      deficiency.
AB  - Early iron deficiency (ID) is one of the most common nutrient deficiencies in
      both developed and developing countries. This condition has been linked to
      perturbations in myelin formation, alterations of monoamine neurotransmitter
      systems particularly in the striatum, and deficits in energy metabolism
      particularly in the hippocampus (HP) and prefrontal cortex (PFC) in rats. Early
      ID has also been traced to long-term behavioral consequences in children in
      domains linked to these neuropathologies. The current experiment assesses
      formerly iron deficient (FID) adult rats on a delayed alternation (DA) task - a
      procedure thought to be sensitive to PFC dysfunction. Rat dams were started on an
      iron deficient chow at gestational day (G) 2 and maintained on this diet until
      postnatal day (P) 7; behavioral training began at P 65 when animals were iron
      replete. FID animals exhibited accelerated acquisition (p=0.002) and fewer errors
      (p=0.003) on the DA task compared to controls. These findings may reflect an
      imbalance between hippocampal and prefrontal modulation of this behavior most
      likely emanating from long-term hippocampal disinhibition by early ID that
      persists in spite of early iron treatment from P 7.

PMID- 20688094
TI  - Selective inhibition of the cellular sodium pump by emicymarin and 14beta
      anhydroxy bufadienolides.
AB  - Partial inhibition of the sodium pump (Na/K-ATP-ase) by a circulating inhibitor
      is known to occur in humans. The objectives of this study were to determine the
      effects of novel bufadienolides lacking an oxygen at C14 on sodium pumps in human
      erythrocytes and leucocytes, dog kidney and pig brain and to document the
      importance of the stereochemistry at C17 on the ability to inhibit these sodium
      pumps. 14alpha bufadienolides were weak inhibitors of all preparations studied.
      3beta-OH,5beta,14beta bufadienolide produced near-total inhibition of dog kidney
      and pig brain Na/K-ATP-ase. Over the same concentration range, it maximally
      inhibited the sodium pump of erythrocytes by 70% and leucocytes by 47%. The
      inhibition profile induced in the leucocyte sodium pump deviated significantly
      from the simple sigmoidal relationship present in the other preparations over the
      3*10(-5) to 1*10(-7) mol/l concentration range. Allo-emicymarin (17alpha) was
      confirmed to be a weak inhibitor of the sodium pump/ATP-ase compared with
      emicymarin (17beta) but both were weaker inhibitors of the leucocyte sodium pump
      than that of the other preparations. Molecules with the C14 in the beta
      configuration are more efficacious than in the alpha configuration. In the case
      of emicymarin, the attachment of the furone at C17 in the alpha configuration
      results in substantially weaker inhibitory activity than in the beta
      configuration, seen in most cardenolides and bufadienolides. Unlike ouabain and
      bufalin that show no specificity of action in these preparations, 3beta-
      OH,5beta,14beta bufadienolide selectively inhibits the activity of at least one
      low-prevalence subset of the leucocyte Na/K-ATP-ase.

PMID- 20688095
TI  - Population based evaluation of a multi-parametric steroid profiling on
      administered endogenous steroids in single low dose.
AB  - Steroid profiling provides valuable information to detect doping with endogenous
      steroids. Apart from the traditionally monitored steroids, minor metabolites can
      play an important role to increase the specificity and efficiency of current
      detection methods. The applicability of several minor steroid metabolites was
      tested on administration studies with low doses of oral testosterone (T), T gel,
      dihydrotestosterone (DHT) gel and oral dehydroepiandrosterone (DHEA). The
      collected data for all monitored parameters were evaluated with the respective
      population based reference ranges. Besides the traditional markers T/E, T and
      DHT, minor metabolites 4-OH-Adion and 6alpha-OH-Adion were found as most
      sensitive metabolites to detect oral T administration. The most sensitive
      metabolites for the detection of DHEA were identified as 16alpha-OH-DHEA and
      7beta-OH-DHEA but longest detection up to three days (after oral administration
      of 50 mg) was obtained with non-specific 5beta-steroids and its ratios. Steroids
      applied as a gel had longer effects on the metabolism but were generally not
      detectable with universal decision criteria. It can be concluded that population
      based reference ranges show limited overall performance in detecting misuse of
      small doses of natural androgens. Although some minor metabolites provide
      additional information for the oral testosterone and DHEA formulations, the
      topical administered steroids could not be detected for all volunteers using
      universal reference limits. Application of other population based threshold
      limits did not lead to longer detection times.

PMID- 20688097
TI  - Domoic acid induced seizures progress to a chronic state of epilepsy in rats.
AB  - The emergence of an epilepsy syndrome in sea lions poisoned by domoic acid (DA)
      draws striking parallels to the single case study of temporal lobe epilepsy (TLE)
      that developed in an 84 yr old man one year after being poisoned by DA. To
      establish a basis for understanding this disease in sea lions and humans that
      appears to progress from DA poisoning, we have investigated the potential for a
      single incident of DA poisoning in rats to progress to spontaneous recurrent
      seizures (SRS), the hallmark of epilepsy. We have developed a DA administration
      protocol to induce a nonlethal status epilepticus (SE) and monitored the animals
      for SRS by 6 h/week of video recording. We demonstrate that a single episode of
      SE leads to SRS in 94% of rats (n = 23) in 6 months. These findings indicate that
      DA induced SE can efficiently translate to epileptic disease.

PMID- 20688098
TI  - Mitochondrial dysfunction in Caenorhabditis elegans causes metabolic
      restructuring, but this is not linked to longevity.
AB  - Lifespan in Caenorhabditis elegans, Drosophila, and mice can be extended by a
      decrease in mitochondrial electron transport chain (ETC) function, but the
      mechanism behind this extension is unknown. In the present study, we combine
      detailed metabolic analysis with lifespan determination following suppression of
      individual genes encoding respiratory complexes I-IV. We report that reduced
      complexes I, III, and IV activity extend lifespan but that complex II disruption
      does not. However, disruption to all four complexes affected metabolism in a
      similar manner suggesting that metabolic effects induced by ETC disruption are
      separable from lifespan extension. We found that suppression of ETC components
      induces a starvation-like metabolic response via the nuclear hormone receptor NHR
      49. This includes induction of genes for mitochondrial fatty-acid beta-oxidation
      (acs-2), the glyoxylate cycle (gei-7), gluconeogensis (PEPCK), and glycolysis
      (gpd-3). Interestingly, a null mutation of nhr-49 attenuated induction of these
      metabolic pathways, but did not affect the lifespan extension associated with
      decreases in complexes I, III, and IV function. Together, our results suggest
      that restructuring of metabolism via NHR-49 in C. elegans with mitochondrial
      dysfunction does not cause lifespan extension.

PMID- 20688100
TI  - New approaches to the pharmacological treatment of obesity: can they break
      through the efficacy barrier?
AB  - In this review we assess the range of centrally active anorectics that are either
      in human clinical trials, or are likely to be so in the near future. We describe
      their weight loss efficacy, mode of action at both pharmacological and
      behavioural levels, where understood, together with the range of side effects
      that might be expected in clinical use. We have however evaluated these compounds
      against the considerably more rigorous criteria that are now being used by the
      Federal Drugs Agency and European Medicines Agency to decide approvals and market
      withdrawals. Several trends are evident. Recent advances in the understanding of
      energy balance control have resulted in the exploitation of a number of new
      targets, some of which have yielded promising data in clinical trials for weight
      loss. A second major trend is derived from the hypothesis that improved weight
      loss efficacy over current therapy is most likely to emerge from treatments
      targeting multiple mechanisms of energy balance control. This reasoning has led
      to the development of a number of new treatments for obesity where multiple
      mechanisms are targeted, either by a single molecule, such as tesofensine, or
      through drug combinations such as qnexa, contrave, empatic, and
      pramlintide+metreleptin. Many of these approaches also utilise advances in
      formulation technology to widen safety margins. Finally, the practicality of
      peptide therapies for obesity has become better validated in recent studies and
      this may allow more rapid exploitation of novel targets, rather than awaiting the
      development of orally available small molecules. We conclude that novel, more
      efficacious and better tolerated treatments for obesity may become available in
      the near future.

PMID- 20688101
TI  - Electrospinning of silk fibroin and collagen for vascular tissue engineering.
AB  - Tubular scaffolds of silk fibroin (SF)/collagen (Col) were prepared by
      electrospinning with the aim to develop a new scaffold for vascular tissue
      engineering. The effects of the solvent, solution concentration and collagen
      content on the morphology of the scaffolds were investigated by SEM. FTIR and XRD
      were used to investigate their structural changes. Although there were
      morphological and structural differences, the water uptake and the tensile
      strength of the scaffolds with different collagen content showed no significant
      difference. This study confirmed the feasibility of the fabrication of SF/Col
      tubular scaffold by electrospinning from aqueous solution and provided promising
      tubular scaffold for vascular tissue engineering.

PMID- 20688099
TI  - The neurobiology of pair bonding: insights from a socially monogamous rodent.
AB  - The formation of enduring relationships between adult mates (i.e., pair bonds) is
      an integral aspect of human social behavior and has been implicated in both
      physical and psychological health. However, due to the inherent complexity of
      these bonds and the relative rarity with which they are formed in other mammalian
      species, we know surprisingly little about their underlying neurobiology. Over
      the past few decades, the prairie vole (Microtus ochrogaster) has emerged as an
      animal model of pair bonding. Research in this socially monogamous rodent has
      provided valuable insight into the neurobiological mechanisms that regulate pair
      bonding behaviors. Here, we review these studies and discuss the neural
      regulation of three behaviors inherent to pair bonding: the formation of partner
      preferences, the subsequent development of selective aggression toward unfamiliar
      conspecifics, and the bi-parental care of young. We focus on the role of
      vasopressin, oxytocin, and dopamine in the regulation of these behaviors, but
      also discuss the involvement of other neuropeptides, neurotransmitters, and
      hormones. These studies may not only contribute to the understanding of pair
      bonding in our own species, but may also offer insight into the underlying causes
      of social deficits noted in several mental health disorders.

PMID- 20688102
TI  - Delayed akinetic catatonic mutism following methadone overdose.
AB  - A 49-year-old woman developed a catatonic mute state a few weeks after methadone
      overdose. Clinical, radiological and histological findings were consistent with
      toxic spongiform leukoencephalopathy, which adds a potentially deadly side-effect
      to a generally considered safe substitution for heroin.

PMID- 20688103
TI  - An implicit measure of olfactory performance for non-human primates reveals
      aversive and pleasant odor conditioning.
AB  - We have little understanding of how odorants are processed in neural networks of
      the primate brain. Because chemo-stimuli are harder to control than physical
      stimuli (e.g. vision, audition), such research was limited by the temporal
      resolution, accuracy, and reliability of olfactometers (odor producing machines).
      Recent advances were able to create olfactometers that overcome these
      limitations, allowing their use together with neuroimaging techniques in humans.
      From the behavioral point of view, olfaction research requires a behavioral
      measure that can be used to quantify olfactory performance. This becomes a real
      problem when working with animals, where, unlike humans, explicit measures are
      harder to obtain. Furthermore, because odorants are powerful primitive
      reinforcers, such implicit measures can be beneficial to use in learning
      paradigms. Here we describe an olfactometer suitable for use in non-human
      primates, and an end-port design that allows the accurate measure of real-time
      respiratory modulations that are elicited in response to odor presentation. We
      demonstrate that this implicit measure is differentially modulated when
      experiencing pleasant or aversive odors. We then present an experimental paradigm
      in which monkeys learn to associate tones with odors, and show that the time
      delay from the conditioned stimuli to the next breath can be used to measure
      learning and memory expression in this paradigm. Using this construct, we reveal
      olfactory performance during acquisition and extinction of odor conditioning.
      These techniques can be used in electrophysiological recordings from relevant
      brain areas to shed light on neural networks involved in odor processing and
      reinforcement-learning.

PMID- 20688104
TI  - Fully exploratory network ICA (FENICA) on resting-state fMRI data.
AB  - Independent component analysis (ICA) is one of the most valuable explorative
      methods for analyzing resting-state networks (RSNs) in fMRI, representing a data
      driven approach that enables decomposition of high-dimensional data into discrete
      components. Extensions to a group-level suffer from the drawback of evaluating
      single-subject resting-state components of interest either using a predefined
      spatial template or via visual inspection. FENICA introduced in the context of
      group ICA methods is based solely on spatially consistency across subjects
      directly reflecting similar networks. Therefore, group data can be processed
      without further visual inspection of the single-subject components or the
      definition of a template (Schopf et al., 2009). In this study FENICA was applied
      to fMRI resting-state data from 28 healthy subjects resulting in eight group
      RSNs. These RSNs resemble the spatial patterns of the following previously
      described networks: (1) visual network, (2) default mode network, (3)
      sensorimotor network, (4) dorsolateral prefrontal network, (5) temporal
      prefrontal network, (6) basal ganglia network, (7) auditory processing network,
      and (8) working memory network. This novel analysis approach for identifying
      spatially consistent networks across a group of subjects does not require manual
      or template-based selection of single-subject components and, therefore, offers a
      truly explorative procedure of assessing RSNs.

PMID- 20688105
TI  - Characterization of a 3-vessel occlusion model for the induction of complete
      global cerebral ischemia in mice.
AB  - Existing murine models of global cerebral ischemia are technically challenging
      thereby hampering the use of genetically engineered mice to study cardiac arrest
      induced brain damage. We therefore investigated, if disconnecting the cerebral
      circulation from vertebral collateral blood flow by proximal occlusion of the
      basilar artery together with temporary bilateral common carotid artery occlusion
      (BCCAo) may be a more feasible approach. C57/Bl6 mice were anesthetized and the
      basilar artery was occluded through a ventral approach. Ten days later BCCAo was
      performed for 8-14min. Increasing durations of ischemia resulted in enhanced
      neuronal cell death in cortex, striatum, and hippocampus (22-63%) and increased
      neurological dysfunction and mortality (0-36%). Following 10min of BCCAo, the
      duration of global ischemia with the most favorable mortality/neuronal cell death
      ratio, hippocampal damage started 6h after the insult while cortical and striatal
      damage was delayed by at least 24h. No further loss of neuronal cells was
      observed later than 3 days. The proposed two-step approach resulted in complete
      cerebral ischemia and caused neuronal damage with high reproducibility and small
      variability. In combination with transgenic and knock-out mice this technically
      feasible model may help to extend our knowledge on the pathophysiology of cardiac
      arrest-induced brain damage.

PMID- 20688106
TI  - Acute but not chronic administration of pioglitazone promoted behavioral and
      neurochemical protective effects in the MPTP model of Parkinson's disease.
AB  - The present study investigated the neurochemical, motor and cognitive effects of
      pioglitazone in a rat model of Parkinson's disease induced by 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine (MPTP). In the first experiment, we administered MPTP,
      and 1h later administered a single oral dose of pioglitazone (5, 15 and 30
      mg/kg). The following day, we performed the open-field test and neurochemical
      dose response curve. We demonstrated that 30 mg/kg of pioglitazone was capable of
      restoring striatal dopamine (DA) concentrations and motor behaviors. A second
      experiment was conducted to test the effects of two protocols (acute and chronic)
      of pioglitazone (30 mg/kg) administration in the open-field test, two-way active
      avoidance task and in the DA and metabolites levels. The acute protocol consisted
      of a single oral administration 1 h after MPTP, whereas the chronic protocol was
      performed with daily administrations starting 1 h after MPTP and ending 22 days
      after that. Results showed that neither protocol was able to reverse the
      cognitive impairment promoted by MPTP. We also demonstrated that acute treatment
      generated some level of neuroprotection, as confirmed by the absence of DA
      reduction in the group treated with pioglitazone in comparison to the sham group.
      By contrast, chronic treatment leaded to a reduction of striatal DA, close to
      MPTP administration alone. These findings suggest that acute administration of
      pioglitazone (30 mg/kg) was more efficient in generating beneficial effects on
      motor behaviors and in striatal DA levels. Nevertheless, we failed to demonstrate
      that pioglitazone administration improved performance on a dopamine-related
      cognitive task after MPTP.

PMID- 20688107
TI  - Expression of orexin receptors 1 (OX1R) and 2 (OX2R) in the porcine ovary during
      the oestrous cycle.
AB  - Orexins A and B are neuropeptides which are synthesized mainly in the lateral
      hypothalamus and are associated with a variety of physiological functions such as
      energy homeostasis, sleep and wakefulness, feeding behavior, as well as the
      reproductive system. The orexins activate two G-protein-coupled receptors termed
      orexin receptor 1 (OX1R) and orexin receptor 2 (OX2R). The present study analyses
      OX1R and OX2R mRNAs and proteins' expression in the porcine ovary on days 2-3, 10
      12, 14-16 and 17-19 of the oestrous cycle. Using real-time PCR, higher OX1R mRNA
      expression was detected in porcine CLs (p<0.01) than in granulosa and theca
      cells. The expression peak of the OX2R gene occurred in granulosa cells (p<0.05
      in comparison with CLs on days 2-3 and 10-12 of the oestrous cycle). The OX1R
      protein content was higher (p<0.01) in CLs isolated during the luteal phase in
      comparison with follicular cells. The OX2R protein level was more pronounced
      (p<0.05) in CLs on days 10-12 and 14-16 than in the remaining periods of the
      cycle. In conclusion, we demonstrated the presence of OX1R and OX2R genes and
      proteins in the ovary of the pig and the impact of the hormonal milieu on the
      expression of both receptors. Our results suggest that orexins may affect
      reproductive functions.

PMID- 20688108
TI  - Circulating ghrelin and ghrelin to obestatin ratio are low in patients with
      untreated mild-to-moderate hypertension.
AB  - Obestatin, encoded by the same gene as ghrelin, was first described as a
      physiological opponent of ghrelin. We investigated fasting plasma ghrelin and
      obestatin levels and ratio of ghrelin to obestatin in humans with untreated mild
      to-moderate hypertension and humans with normal blood pressure. We found that the
      plasma concentration of ghrelin and the ratio of ghrelin to obestatin were
      significantly lower in hypertension group compared with control group (236.3+/
      12.3 pg/ml vs 381.4+/-25.6 pg/ml, P<0.01; 0.89+/-0.06 vs 1.2+/-0.06, P<0.01). The
      plasma concentration of obestatin was lower in hypertension group compared with
      control group, but the difference between the two groups was not significant
      (276.2+/-15.1 pg/ml vs 325.4+/-25.8 pg/ml, P>0.05). In a multiple regression
      model, systolic blood pressure, triglyceride and obestatin were independent
      predictors of ghrelin (standardized coefficient=-0.332; P=0.019; standardized
      coefficient=-0.302; P=0.030; standardized coefficient=0.630; P<0.0005,
      respectively). In another multiple regression model, only ghrelin was an
      independent predictor of obestatin (standardized coefficient=0.861; P<0.0005).
      Both systolic blood pressure and triglyceride were independent predictors of
      ratio of ghrelin to obestatin (standardized coefficient=-0.385; P=0.033;
      standardized coefficient=-0.430; P=0.018, respectively). Our data suggests that
      there are disturbances of ghrelin and obestatin in the circulating plasma of
      humans and the ghrelin/obestatin system might play a role in blood pressure
      regulation.

PMID- 20688109
TI  - Methods for building an inexpensive computer-controlled olfactometer for
      temporally-precise experiments.
AB  - Many human olfactory experiments call for fast and stable stimulus-rise times as
      well as exact and stable stimulus-onset times. Due to these temporal demands, an
      olfactometer is often needed. However, an olfactometer is a piece of equipment
      that either comes with a high price tag or requires a high degree of technical
      expertise to build and/or to run. Here, we detail the construction of an
      olfactometer that is constructed almost exclusively with "off-the-shelf" parts,
      requires little technical knowledge to build, has relatively low price tags, and
      is controlled by E-Prime, a turnkey-ready and easily-programmable software
      commonly used in psychological experiments. The olfactometer can present either
      solid or liquid odor sources, and it exhibits a fast stimulus-rise time and a
      fast and stable stimulus-onset time. We provide a detailed description of the
      olfactometer construction, a list of its individual parts and prices, as well as
      potential modifications to the design. In addition, we present odor onset and
      concentration curves as measured with a photo-ionization detector, together with
      corresponding GC/MS analyses of signal-intensity drop (5.9%) over a longer period
      of use. Finally, we present data from behavioral and psychophysiological
      recordings demonstrating that the olfactometer is suitable for use during event
      related EEG experiments.

PMID- 20688110
TI  - Differential effects of active attention and age on event-related potentials to
      visual and olfactory stimuli.
AB  - Normal aging impairs olfactory functioning both centrally and peripherally. The
      P3 peak of the event-related potential (ERP), evoked by active response to a
      target stimulus, is considered a reflection of central cognitive processing. It
      can also be evoked in a passive task to both auditory and visual stimuli. Our
      goal was to investigate whether age influences amplitude and latency of the ERP
      differentially in active and passive tasks to olfactory stimuli. Olfactory and
      visual event-related potentials were elicited with a single stimulus paradigm in
      separate active and passive task response conditions. Participants included 30
      healthy individuals from three age groups, young, middle age, and older adults.
      Results indicated that P3 ERP latency increased with age in both sensory
      modalities. P3 latencies for active versus passive tasks were similar across age
      groups for visual ERPs, but in the olfactory modality, older adults demonstrated
      significantly longer latencies in the passive task compared to the active task.
      Future directions should include research on specific clinical populations
      utilizing active versus passive task conditions.

PMID- 20688111
TI  - Ageing, depression, anxiety, social support and the diurnal rhythm and awakening
      response of salivary cortisol.
AB  - The present study compared the cortisol awakening response and diurnal rhythm in
      24 young healthy students and 48 community-dwelling older adults. The
      associations with diurnal cortisol and depression, anxiety and social support
      were also examined in relation to age. Salivary cortisol was measured over the
      course of one day: immediately upon awakening, 30 min later, and then 3h, 6h, 9h
      and 12h post-awakening. Participants completed a questionnaire measuring symptoms
      of anxiety and depression and social support was assessed. Older adults exhibited
      a significantly reduced awakening response, overall cortisol levels, area under
      the curve (AUC) and diurnal slopes than younger adults, resulting in a flatter
      diurnal rhythm. Younger adults with higher depression scores had significantly
      higher overall cortisol and higher levels upon awakening and 30 min post
      awakening. In the younger adults, anxiety and depression correlated positively
      with AUC and the cortisol awakening response (CAR). Older adults with lower
      social support had a reduced AUC where younger adults with lower social support
      displayed a larger AUC. These findings suggest that the diurnal rhythm and
      awakening response of salivary cortisol are significantly reduced in older adults
      and the associations between anxiety, depression and social support and diurnal
      cortisol vary with age.

PMID- 20688112
TI  - Right frontopolar cortex activity correlates with reliability of retrospective
      rating of confidence in short-term recognition memory performance.
AB  - Human memory systems contain self-monitoring mechanisms for evaluating their
      progress. People can change their learning strategy on the basis of confidence in
      their performance at that time. However, it has not been fully understood how the
      brain is engaged in reliable rating of confidence in past recognition memory
      performance. We measured the brain activity by fMRI while healthy subjects
      performed a visual short-term recognition memory test and then rated their
      confidence in their answers as high, middle, or low. As shown previously, their
      behavioral performance in the confidence rating widely varied; some showed a
      positive confidence-recognition correlation (i.e., "rate reliably") while others
      did not. Among brain regions showing greater activity during rating their
      confidence relative to during a control, non-metamemory task (discriminating
      brightness of words), only a posterior-dorsal part of the right frontopolar
      cortex exhibited higher activity as the confidence level better correlated with
      actual recognition memory performance. These results suggest that activation in
      the right frontopolar cortex is key to a reliable, retrospective rating of
      confidence in short-term recognition memory performance.

PMID- 20688113
TI  - A DNA transposon-based approach to functional screening in neural stem cells.
AB  - We describe the use of DNA transposons as tools for carrying out functional
      screenings in murine embryonic stem (ES) cell-derived neural stem (NS) cells. NS
      cells are a new type of stem cells featuring radial glial properties, that
      undergoes symmetric cell division for an indefinite number of passages, expanding
      as a monolayer. In this model, the previously unreported Sleeping Beauty
      transposase M3A achieves an optimal blend of clone generation efficiency and low
      redundancy of integrations per clone, compared to the SB100X Sleeping Beauty
      variant and to the piggyBac transposon. The technology described here makes it
      possible to randomly trap genes in the NS cell genome and modify their expression
      or tag them with fluorescent markers and selectable genes, allowing recombinant
      cells to be isolated and expanded clonally. This approach will facilitate the
      identification of novel determinants of stem cell biology and neural cell fate
      specification in NS cells.

PMID- 20688114
TI  - Intracellular delivery and anti-cancer effect of self-assembled heparin-Pluronic
      nanogels with RNase A.
AB  - A novel self-assembled nanogel was prepared for the intracellular delivery of
      ribonuclease A (RNase A) and the anti-cancer efficacy of RNase A delivery was
      investigated. The physical properties of self-assembled heparin-Pluronic (HP)
      nanogels incorporating RNase A (HPR nanogels) were characterized by dynamic light
      scattering (DLS), xi-potential, and transmission electron microscopy (TEM). RNase
      A showed a strong affinity for the HP nanogel, resulting in a high loading
      efficiency (>78%) and significantly decreased hydrodynamic size (from 89 to ~29).
      HPR nanogels were efficiently internalized into HeLa cells and localized in the
      cytosol as well as the nucleus. In the mechanism study of cellular uptake,
      treating with methoxy beta-cyclodextrin (Mbeta-CD) decreased the uptake
      efficiency of HP nanogel, indicating that internalization occurs via
      caveolae/lipid-raft mediated endocytosis. Localization in the nucleus most likely
      occurred because the conjugated heparin facilitated nucleus penetration. The
      cytotoxicity of HPR nanogels was significantly increased when the RNase A
      concentration was increased, which resulted from the degradation of single
      stranded RNAs in the cytosol and the nucleus due to the intracellular
      localization of the HPR nanogels. These results demonstrate that self-assembled
      HP nanogels are a remarkable vehicle for intracellular protein delivery and hold
      promise for use as cancer chemotherapeutics.

PMID- 20688115
TI  - Towards graft-specific immune suppression: Gene therapy of the transplanted
      kidney.
AB  - Kidney transplantation remains the best therapeutic option for patients with end
      stage renal disease. Immunosuppressive therapy has largely resolved the issue of
      acute transplant rejection. However, because of its systemic nature,
      immunosuppressive therapy trades off efficacy against side-effects and its
      chronic use has been associated with severe infections and malignancy. Moreover,
      long-term survival of renal grafts did not change over the past twenty years.
      This situation may be improved by using gene therapy as an alternative or add-on
      strategy to the classic, systemic immune suppression. This review discusses gene
      therapy approaches in kidney transplantation by addressing the essentials of
      delivery vectors and by outlining strategies to achieve local immunosupression
      and allograft-specific tolerance, both in acute rejection and chronic transplant
      dysfunction. Employing such strategies, local suppression of the immune response
      and induction of transplantation-specific tolerance have been accomplished in
      experimental gene therapy. If successful in the clinical setting, gene therapy
      may (partially) substitute systemic, non-selective immunosuppressive medication,
      with a major impact on the quality of life and survival of the transplanted
      patients as well as on the waiting time for receiving a renal graft.

PMID- 20688116
TI  - A simple approach for the preparation of mature human relaxin-3.
AB  - Relaxin-3 (also known as INSL7) is the most recently identified member of the
      insulin-like family. It is predominantly expressed in the nucleus incertus of the
      brain and involved in the control of stress response, food intake, and
      reproduction. In the present work, we have established a simple approach for the
      preparation of the mature human relaxin-3 peptide. We first designed and
      recombinantly expressed a single-chain relaxin-3 precursor in E. coli cells.
      After purification by immobilized metal ion affinity chromatography, refolding in
      vitro through disulfide reshuffling, and digestion by endoproteinase Asp-N,
      mature human relaxin-3 was obtained in high yield and at low cost. Peptide
      mapping and circular dichroism spectroscopy studies suggested that the
      recombinant relaxin-3 adopted an insulin-like fold with the expected disulfide
      linkages. The recombinant mature relaxin-3 was fully active in both RXFP3 binding
      and activation assays. The activity of the single-chain precursor was very low,
      suggesting that a free C-terminus of the B-chain is necessary for receptor
      binding and activation of relaxin-3. Our present work provides a highly efficient
      approach for the preparation of relaxin-3 as well as its analogues for functional
      and structural analyses.

PMID- 20688118
TI  - The anorexigenic effect of cholecystokinin octapeptide in a goldfish model is
      mediated by the vagal afferent and subsequently through the melanocortin- and
      corticotropin-releasing hormone-signaling pathways.
AB  - We have been extensively investigating the mechanisms by which neuropeptides
      regulate feeding behavior by using a goldfish (Carassius auratus) model. In this
      species, the anorexigenic action of melanocortin peptide is centrally mediated
      via the corticotropin-releasing hormone (CRH)/CRH receptor neuronal system,
      whereas sulfated cholecystokinin octapeptide (CCK-8s) is involved in the appetite
      regulation as a peripheral anorexigenic factor. The aim of the present study was
      to identify the mechanism of the anorexigenic effect of peripherally injected CCK
      8s, which has not yet been identified in goldfish. Co-administration of
      capsaicin, a neurotoxin that destroys primary sensory afferents, at 100 nmol/g
      BW, blocked the anorexigenic action of intraperitoneally injected CCK-8s (100
      pmol/g BW), whereas the anorexigenic action of intracerebroventricularly injected
      CCK-8s (5 pmol/g BW) was not blocked by co-administration of capsaicin. Pre
      treatment with a specific CRH receptor antagonist, alpha-helical CRH((9-41)),
      attenuated the anorexigenic action of CCK-8s. The expression level of CRH mRNA in
      the diencephalic tissue of the CCK-8s-injected group was not changed, but the
      level of proopiomelanocortin mRNA was significantly increased at 1h after
      treatment. Therefore, we have identified for the first time that the reduction of
      appetite induced by peripherally injected CCK-8s in goldfish appears to be
      mediated by the vagal afferent and subsequently through the melanocortin- and
      corticotropin-releasing hormone-signaling pathways.

PMID- 20688119
TI  - Serotonin has kinin-like activity in stimulating secretion by Malpighian tubules
      of the house cricket Acheta domesticus.
AB  - Serotonin stimulates secretion by Malpighian tubules (MT) of a number of insects,
      and functions as a diuretic hormone in Rhodnius prolixus and in larval Aedes
      aegypti. Serotonin is here shown to be a potent stimulant of secretion by MT of
      the house cricket, Acheta domesticus, with an apparent EC(50) of 9.4 nmol L(-1),
      although its diuretic activity is just 25% of the maximum achievable with either
      the native CRF-related peptide, Achdo-DH, or a crude extract of the corpora
      cardiaca. In this respect, the diuretic activity of serotonin is similar to that
      of the cricket kinin Achdo-KI, and when tested together their actions are not
      additive, which suggests they target the same transport process. Consistent with
      this suggestion, the activity of serotonin is chloride-dependent and is
      associated with a non-selective stimulation of NaCl and KCl transport. In common
      with Achdo-KI, serotonin has no effect on cAMP production by isolated MT, and
      both act synergistically with exogenous 8bromo-cAMP in stimulating fluid
      secretion, most likely by promoting the release of Ca(2+) from intracellular
      stores. A number of serotonin agonists and antagonists were tested to determine
      the pharmacological profile of receptors on cricket MT. The results are
      consistent with the diuretic activity of serotonin being mediated through a 5
      HT(2)-like receptor.

PMID- 20688117
TI  - Solid-phase peptide head-to-side chain cyclodimerization: discovery of C(2)
      symmetric cyclic lactam hybrid alpha-melanocyte-stimulating hormone (MSH)/agouti
      signaling protein (ASIP) analogues with potent activities at the human
      melanocortin receptors.
AB  - A novel hybrid melanocortin pharmacophore was designed based on the
      pharmacophores of the agouti-signaling protein (ASIP), an endogenous melanocortin
      antagonist, and alpha-melanocyte-stimulating hormone (alpha-MSH), an endogenous
      melanocortin agonist. The designed hybrid ASIP/MSH pharmacophore was explored in
      monomeric cyclic, and cyclodimeric templates. The monomeric cyclic disulfide
      series yielded peptides with hMC3R-selective non-competitive binding affinities.
      The direct on-resin peptide lactam cyclodimerization yielded nanomolar range (25
      120 nM) hMC1R-selective full and partial agonists in the cyclodimeric lactam
      series which demonstrates an improvement over the previous attempts at
      hybridization of MSH and agouti protein sequences. The secondary structure
      oriented pharmacophore hybridization strategy will prove useful in development of
      unique allosteric and orthosteric melanocortin receptor modulators. This report
      also illustrates the utility of peptide cyclodimerization for the development of
      novel GPCR peptide ligands.

PMID- 20688120
TI  - alpha-Melanocyte-stimulating hormone (alpha-MSH) reverses impairment of memory
      reconsolidation induced by interleukin-1 beta (IL-1 beta) hippocampal infusions.
AB  - Interleukin-1 beta (IL-1beta) significantly influences cognitive processes.
      Treatments which raise the level of IL-1beta in the brain impair memory
      consolidation in contextual fear conditioning. However, the effect of IL-1beta on
      memory reconsolidation has not yet been established. The melanocortin alpha
      melanocyte-stimulating hormone (alpha-MSH) exerts potent anti-inflammatory
      actions by antagonizing the effect of proinflammatory cytokines. Five subtypes of
      melanocortin receptors (MC1R-MC5R) have been identified, of which MC3R and MC4R
      are predominant in the central nervous system. The present experiments show that
      the injection of IL-1beta (5 ng/0.25 MUl) in dorsal hippocampus up to 30 min
      after re-exposition to the context decreases freezing during the contextual fear
      test. Impairment of memory reconsolidation was reversed by treatment with alpha
      MSH (0.05 MUg/0.25 MUl). Administration of the MC4 receptor antagonist HS014 (0.5
      MUg/0.25 MUl) blocked the effect of alpha-MSH. These results suggest that IL
      1beta may influence memory reconsolidation and that activation of central MC4R
      could lead to improve cognitive performance.

PMID- 20688121
TI  - Vasoactive intestinal peptide induces surfactant protein A expression in ATII
      cells through activation of PKC/c-Fos pathway.
AB  - Vasoactive intestinal peptide (VIP) is a major neurotransmitter in the lungs and
      regulates many aspects of pulmonary functions. Pulmonary surfactant (PS), a
      complex mixture of lipids and proteins, produced by the alveolar type II (ATII)
      cells maintains alveolar integrity and plays important roles in the control of
      host defense and inflammation in the lungs. Surfactants deficiency or dysfunction
      is associated with occurrence and development of many pulmonary diseases. We
      reported previously that VIP enhanced the synthesis of pulmonary surfactants
      phospholipid in ATII cells. In this study, the effect of VIP on the expression of
      pulmonary surfactant protein A (SP-A) in lung explants was investigated. Firstly,
      we found that VIP elevated SP-A expression in ATII cells which was mediated by
      enhanced sp-a gene transcription. Furthermore, we identified that c-Fos protein
      was essential for VIP induced SP-A expression in ATII cells. Finally, we provided
      evidence to show that activation of c-Fos expression by PKC was required for VIP
      induced SP-A expression. Altogether, our work showed that VIP regulated the
      function of pulmonary surfactant system in the lungs and further investigation of
      the underlying mechanism would provide important clues for better therapeutic
      strategy design for pulmonary disorders caused by surfactant deficiency.

PMID- 20688122
TI  - Trp-His, a vasorelaxant di-peptide, can inhibit extracellular Ca2+ entry to rat
      vascular smooth muscle cells through blockade of dihydropyridine-like L-type Ca2+
      channels.
AB  - Our previous findings regarding the biological activities of small peptides
      revealed that a di-peptide, Trp-His (WH), could play a role in the prevention of
      vascular lesions, including cell proliferation and atherosclerosis. Its
      vasoprotective effects could be associated with suppression of the
      vasocontraction signaling cascade, but the underlying mechanism(s) remains
      obscure. In this study, we attempted to elucidate the vasoprotective mechanism of
      WH, in opposing the proliferation of rat vascular smooth muscle cells (VSMCs). In
      VSMCs from 8 week-old male Wistar rat thoracic aortae, WH evoked a significant
      dose-dependent anti-proliferation effect, without cytotoxicity. In mitogen
      stimulated cell experiments, 300 MUM WH inhibited cytosolic Ca(2+) elevation in
      VSMCs induced by 10 MUM angiotensin II (Ang II). Furthermore, WH suppressed
      extracellular Ca(2+) entry into CaCl(2)-stimulated VSMCs. The biological capacity
      of WH as an intracellular Ca(2+) ([Ca(2+)](i)) suppressor was also proven when 50
      MUM Bay K8644 was used to enhance Ca(2+) entry via a voltage-dependent l-type
      Ca(2+) channel (VDCC) and 300 MUM WH elicited a 23% reduction in [Ca(2+)](i). The
      absence of a reduction of the [Ca(2+)](i) by the mixture of tryptophan and
      histidine revealed the importance of the peptide backbone in the [Ca(2+)](i)
      reduction effect. Furthermore, the WH-induced [Ca(2+)](i) reduction was abolished
      by verapamil, but not by nifedipine, indicating that WH likely binds to an
      extracellular site of the VDCC at a site similar to that of the dihydropyridine
      type-Ca(2+) channel blockers.

PMID- 20688123
TI  - Nisin inhibits dental caries-associated microorganism in vitro.
AB  - Nisin, produced by Lactococcus lactis, is an antibiotic peptide to effectively
      antagonize a broad spectrum of Gram-positive bacteria, and is widely used as a
      safe food antimicrobial agent. In the present study, we investigated whether
      nisin could be used as an effective antibiotic peptide against the nine common
      cariogenic microorganisms, and its antimicrobial activity could be affected by
      the ingredients of saliva in oral cavity. In the minimal inhibitory concentration
      (MIC) and minimal bactericide concentration (MBC) and spot-on-lawn assay, nisin
      displayed different MIC, MBC and antimicrobial activity against the nine tested
      strains. There was statistical difference between the inhibitory zone diameters
      of nisin against the different tested bacteria (p<0.05), but no statistical
      difference between the inhibitory zone diameters of nisin dissolved in PBS and
      saliva (p>0.05). Furthermore, morphology and membranes of Streptococcus
      sanguinis, Streptococcus mutans, Lactobacillus fermenti and Lactobacillus
      acidophilus with nisin treatment were observed and showed different degrees of
      variation by a Field Emission Scanning Electron Microscope (FE-SEM). Our findings
      suggested that nisin has considerable potential for prevention and treatment of
      dental caries.

PMID- 20688124
TI  - TTC-based risk assessment of tetrachlorobutadienes and pentachlorobutadienes--the
      in vitro genotoxic contaminants in ground and drinking water.
AB  - Tetrachlorinated butadienes (TetraCBDs), pentachlorinated butadienes (PentaCBDs)
      and hexachlorobutadiene (HexaCBD) were detected in groundwater wells of drinking
      water supplier near Basel up to maximally 157 ng/L (sum value), 15 ng/L (sum
      value), and <50 ng/L, in 2006. HexaCBD is toxicologically well characterized and
      the WHO has derived a TDI of 0.2 MUg/kg body weight (bw)/day and a drinking-water
      guideline value of 600 ng/L. However, due to insufficient toxicity data, neither
      health-based guideline values nor maximum contaminant levels have been
      established for the TetraCBDs and PentaCBDs yet. Since TetraCBDs and PentaCBDs
      show structural alerts for potential genotoxicity, the genotoxicity of TetraCBDs
      and PentaCBDs was examined in vitro. All the TetraCBDs and PentaCBDs as well as
      HexaCBD were clastogenic in the chromosome aberration test. In addition, 1,1,3,4
      TetraCBD and 1,2,3,4-TetraCBD were positive in the Ames test while the other
      polychlorinated butadienes including HexaCBD were negative. Using the threshold
      of toxicological concern (TTC) concept, the target value for TetraCBDs and
      PentaCBDs in drinking water was set at 75 ng/L (sum value of both substance
      groups). For the main component 1,1,4,4-TetraCBD, which is negative in the Ames,
      it is recommended to perform a third in vitro genotoxicity test, the HPRT test,
      before it can be decided whether to refer to the guideline value of HexaCBD at
      600 ng/L or still to use the conservative TTC-based target value of 75 ng/L.

PMID- 20688125
TI  - Mother-offspring dialogue in early pregnancy: impact of adverse environment on
      pregnancy maintenance and neurobiology.
AB  - The mother-offspring dialogue begins even before implantation and is essential to
      signal pregnancy, establish robust contact, and maintain embryo growth and
      development. Any circumstance that disrupts the dialogue risks pregnancy
      problems. A new look at how stress impacts on pregnancy involves its adverse
      effects on the key pregnancy hormones of progesterone and prolactin. These
      effects have far-reaching consequences on pregnancy maintenance, maternal anxiety
      and embryo programming. This review focuses on early pregnancy and how stress
      might compromise the multi-layer, two-way communication between mother and
      embryo.

PMID- 20688126
TI  - Schneiderian first rank symptoms and inferior parietal lobule cortical thickness
      in antipsychotic-naive schizophrenia.
AB  - Inferior parietal lobule (IPL) is implicated in the pathogenesis of first rank
      symptoms (FRS) in schizophrenia by functional neuroimaging studies. However, the
      relationship between IPL cortical thickness and FRS is yet to be explored. In
      this study, cortical thickness of IPL was analyzed in antipsychotic-naive
      schizophrenia patients (total number = 51) with [FRS(+); N = 25] and those
      without FRS [FRS(-); N = 26] in comparison with group-matched healthy controls (N
      = 47). FRS(+) patients showed significant cortical thickness deficit in right IPL
      (specifically angular gyrus) in comparison with both FRS(-) patients (p = 0.005)
      and healthy controls (p = 0.0002); lack of difference on the left side might
      possibly be related to larger variance in healthy controls. Deficient cortical
      thickness involving IPL in FRS(+) schizophrenia patients adds further support to
      the role of internal monitoring system in the pathogenesis of FRS in
      schizophrenia.

PMID- 20688127
TI  - Selective toxicity of dihydroartemisinin on human CD34+ erythroid cell
      differentiation.
AB  - Artemisinins are safely used in the combination therapy for uncomplicated
      malaria, but their employment during pregnancy is still controversial. In fact,
      animal studies reported that the active metabolite, dihydroartemisinin (DHA),
      causes embryonic erythrocytes depletion, when the treatment is performed during a
      critical period of time. The present study investigates the effect of DHA on
      human developmental erythropoiesis in order to characterize the target erythroid
      stage and to predict the window of susceptibility in human pregnancy. As a model
      for human developmental erythropoiesis, peripheral blood purified, CD34+ cells
      were committed towards erythrocytes and DHA (0.5 or 2 MUM) was added to different
      erythroid stages during 14 days culture. Erythroid differentiation was
      investigated by cytofluorimetric analysis of Glycophorin A expression, by
      morphological analysis and erythroid globin gene expression analysis with real
      time PCR. It was found that the effect of DHA was dependent on the maturation
      stage of erythroid cells. In fact when DHA was added to the pro- and basophilic
      erythroblasts caused a significant dose-dependent inhibition of cell
      proliferation and a significant delay of erythroid differentiation, as measured
      by morphological analysis, expression of Glycophorin A by immunofluorescence and
      of erythroid globin genes by real-time PCR. In contrast, the inhibition of stem
      cells and of early progenitors was transient and masked by the subsequent
      exponential cell growth. No effect was observed on mature erythroid stages. This
      is the first demonstration that DHA affects human erythropoiesis in vitro, in a
      dose- and time-dependent manner; the target population seems to be the pro
      erythroblast and basophilic erythroblast stage, suggesting that DHA toxicity is
      limited to primitive human erythropoiesis. These findings outline the relevance
      of DHA dosage and timing to prevent embryotoxicity and support current WHO
      recommendations of avoiding malaria treatment with artemisinins during the first
      trimester of pregnancy.

PMID- 20688128
TI  - Chondrotoxicity and toxicokinetics of novel quinolone antibacterial agents DC
      159a and DX-619 in juvenile rats.
AB  - Quinolone antibacterial agents are extensively utilized in antimicrobial
      chemotherapy. However, they have been reported to induce arthropathy in juvenile
      animals, and the mechanism has not been clarified. Recently, we have demonstrated
      that Dusp1, Tnfrsf12a, Ptgs2, Fos, Mt1a, Plaur, Mmp3, Sstr1 and Has2 genes change
      in the articular cartilage of juvenile rats with a single oral administration of
      ofloxacin (OFLX), suggesting that these genes are involved in the induction of
      OFLX-induced chondrotoxicity. In the present study, to compare the chondrotoxic
      potential between new synthesized quinolones DC-159a and DX-619, and OFLX, they
      were orally administered by gavage at a dose level of 300 or 900 mg/kg/day to
      male juvenile Sprague-Dawley (SD) rats, 3 weeks of age, for 7 days. Then the
      distal humerus and femur were subjected to microscopic examination. Moreover,
      concentrations of these quinolones in the femoral articular cartilage were
      measured in male juvenile SD rats following a single oral administration at 100,
      300 or 900 mg/kg. Furthermore, gene expression of Dusp1, Tnfrsf12a, Ptgs2, Fos,
      Mt1a, Plaur, Mmp3, Sstr1 and Has2 was investigated in the articular cartilage of
      the distal femur in male juvenile SD rats treated with 900 mg/kg of DC-159a or DX
      619 by quantitative real-time reverse transcription-polymerase chain reaction
      (qRT-PCR) analysis. In a microscopic examination, no changes in the articular
      cartilage were observed in any animal administered DC-159a or DX-619. On the
      contrary, cavity formation and chondrocyte cluster in the cartilage of distal
      humerus and femur were noted in animals receiving OFLX at 300 mg/kg/day or more.
      In toxicokinetic analysis, the maximum concentration (C(max)) value in the
      articular cartilage (cartilage C(max)) of DC-159a or DX-619 at 900 mg/kg was
      lower than that of OFLX at 300 mg/kg. However, the area under the cartilage
      concentration-time curve (cartilage AUC)(0-24h) value of DC-159a or DX-619 at 900
      mg/kg was higher than that of OFLX at 300 mg/kg. In qRT-PCR analysis, up
      regulated Dusp1, Fos and Mt1a, and down-regulated Sstr1 and Has2 genes were seen
      in the femoral articular cartilage of rats given DX-619 or DC-159a at 900 mg/kg.
      However, Tnfrsf12a, Ptgs2, Plaur and Mmp3 genes, which were up-regulated in the
      distal femoral articular cartilage exposed to OFLX, did not increase or slightly
      increased. In conclusion, the penetration of DC-159a or DX-619 into the cartilage
      was low compared with that of OFLX, and no obvious changes in Tnfrsf12a, Ptgs2,
      Plaur and Mmp3 genes were observed in the articular cartilage of juvenile rats
      treated with DC-159a or DX-619, which was likely to be responsible for non
      chondrotoxic potentials of DC-159a and DX-619.

PMID- 20688129
TI  - Enantioselective cytotoxicity of isocarbophos is mediated by oxidative stress
      induced JNK activation in human hepatocytes.
AB  - Recent studies have shown the enantioselectivity of chiral pesticides in
      environmental fate, aquatic toxicity, endocrine disruption and cytotoxicity. Thus
      it is of significance to investigate the molecular mechanisms of chiral
      pesticides enantioselectivity in cytotoxicity. In the present study, we used Hep
      G2 cells as in vitro model to assay cytotoxicity of enantiomers of isocarbophos
      (ICP), a widely used chiral organophosphorus pesticide. The results of cell
      viability assay and cytoflow assay indicated an obvious enantioselective
      hepatocyte toxicity of ICP: (-)-ICP was about two times more toxic than (+)-ICP
      in Hep G2 cells. We found that (-)-ICP, but not (+)-ICP, up-regulated Bax protein
      expression and down-regulated Bcl-2 expression levels, which resulted in an
      increase in Bax/Bcl-2 ratio with the apoptosis co-ordination. Although (-)-ICP
      enantioselectively activated both ERK and JNK, only the specific inhibitor for
      JNK could completely reverse (-)-ICP-induced apoptosis of Hep G2 cells. It
      suggests that (-)-ICP-induced hepatocyte toxicity was more dominantly through the
      sustained activation of JNK pathway, but only partially via ERK cascade.
      Furthermore, (-)-ICP induced ROS production, while (+)-ICP had no effect on ROS
      generation. The antioxidant MnTBAP attenuated (-)-ICP-induced activation of JNK
      and ERK, indicating that the outcome from challenge with (-)-ICP enantiomer
      depends on the oxidative stress-induced activation of a series of signaling
      cascades that promote hepatocyte apoptosis. In conclusion, (-)-ICP
      enantioselectively causes the change of Bax/Bcl-2 ratio, triggers the generation
      of intracellular ROS and sequentially induces sustainable activation of JNK,
      which in turn, results in a decrease in cell viability and an increase in cell
      apoptosis. Our observations provide further insight into enantiomers toxicity
      pathway which is able to differentiate between enantiomer activities at molecular
      level.

PMID- 20688130
TI  - Filters for optimal smoothing of acoustic and electric blink reflex EMG responses
      to determine blink response magnitude.
AB  - The functional (i.e., kinematic) aspects of the blink reflex depend on the size
      of the integrated orbicularis oculi EMG response. Peak amplitude of smoothed
      rectified EMG is often used as an approximation of integrated EMG. A comparison
      was made between the outputs of 24 different smoothing filters, correlating peak
      amplitude of acoustic or electric blink reflexes with integrated EMG. The
      coefficient of determination (R2) was largest (i.e., >=.95 for acoustic and >=.90
      for electric blink reflexes) when using either (1) a first-order resistor
      capacitor filter with a time constant of 50 or 100 ms, (2) a boxcar filter
      averaging 51 or 101 data points, or (3) an unequal-weight finite impulse response
      filter with a cutoff frequency of 5 or 10 Hz. These filters are thus recommended
      when determining peak amplitude. Applying a baseline correction on peak amplitude
      and integrated EMG produced slightly smaller values of R2 compared with
      uncorrected measures.

PMID- 20688131
TI  - Motor imagery beyond the joint limits: a transcranial magnetic stimulation study.
AB  - The processes and neural bases used for motor imagery are also used for the
      actual execution of correspondent movements. Humans, however, can imagine
      movements they cannot perform. Here we explored whether plausibility of movements
      is mapped on the corticospinal motor system and whether the process is influenced
      by visuomotor vs. kinesthetic-motor first person imagery strategy. Healthy
      subjects imagined performing possible or biomechanically impossible right index
      finger movements during single pulse TMS of the left motor cortex. We found an
      increase of corticospinal excitability during motor imagery which was higher for
      impossible than possible movements and specific for the muscle involved in the
      actual execution of the imagined movement. We expand our previous action
      observation studies, suggesting that the plausibility of a movement is computed
      in regions upstream the primary motor cortex, and that motor imagery is a higher
      order process not fully constrained by the rules that govern motor execution.

PMID- 20688132
TI  - Genetic effects on anger control and their interaction with alcohol intoxication:
      a self-report study.
AB  - Individual differences in anger control are important to consider when trying to
      understand intoxicated aggression (Parrott and Giancola, 2004). We explored,
      first, genetic and environmental effects on anger control both in self-reported
      sober and alcohol intoxicated states, and whether the same genetic and
      environmental effects influence it in both these states, and second, a possible
      interaction between genetic effects and alcohol in the control of anger. In the
      population based sample (N=8964) of Finnish twins (18-33 years) and their
      siblings (18 years or older), genetic effects on anger control were found both
      for the self-reported sober (27% for men, 34% for women) and alcohol intoxicated
      states (29% for men, 37% for women), with high genetic correlations (from .77 to
      .85) between these states. Genetic effects (26% for men, 29% for women) were also
      found for the difference in anger control between the self-reported sober and
      alcohol intoxicated states, suggesting the effect of alcohol on anger control
      depends on the genotype of the individual.

PMID- 20688133
TI  - Statistical evidence for power law temporal correlations in exploratory behaviour
      of rats.
AB  - Dynamics of exploratory behaviour of rats and home base establishment is
      investigated. Time series of instantaneous speed of rats was computed from their
      position during exploration. The probability distribution function (PDF) of the
      speed obeys a power law distribution with exponents ranging from 2.1 to 2.32. The
      PDF of the recurrence time of large speed also exhibits a power law, P(tau) ~
      tau(-beta) with beta from 1.56 to 2.30. The power spectrum of the speed is in
      general agreement with the 1/f spectrum reported earlier. These observations
      indicate that the acquisition of spatial information during exploration is self
      organized with power law temporal correlations. This provides a possible
      explanation for the home base behaviour of rats during exploration. The
      exploratory behaviour of rats resembles other systems exhibiting self-organized
      criticality, e.g., earthquakes, solar flares etc.

PMID- 20688134
TI  - Using automated imaging to interrogate gonadotrophin-releasing hormone receptor
      trafficking and function.
AB  - Gonadotrophin-releasing hormone (GnRH) acts via seven transmembrane receptors on
      gonadotrophs to stimulate gonadotrophin synthesis and secretion, and thereby
      mediates central control of reproduction. Type I mammalian GnRHR are unique, in
      that they lack C-terminal tails. This is thought to underlie their resistance to
      rapid homologous desensitisation as well as their slow rate of internalisation
      and inability to provoke G-protein-independent (arrestin-mediated) signalling.
      More recently it has been discovered that the vast majority of human GnRHR are
      actually intracellular, in spite of the fact that they are activated at the cell
      surface by a membrane impermeant peptide hormone. This apparently reflects
      inefficient exit from the endoplasmic reticulum and again, the absence of the C
      tail likely contributes to their intracellular localisation. This review is
      intended to cover some of these novel aspects of GnRHR biology, focusing on ways
      that we have used automated fluorescence microscopy (high content imaging) to
      explore GnRHR localisation and trafficking as well as spatial and temporal
      aspects of GnRH signalling via the Ca(2+)/calmodulin/calcineurin/NFAT and
      Raf/MEK/ERK pathways.

PMID- 20688135
TI  - Specific determinants of conantokins that dictate their selectivity for the NR2B
      subunit of N-methyl-D-aspartate receptors.
AB  - Conantokins are naturally-occurring small peptide antagonists of ion flow through
      NMDA/glycine activated-N-methyl-d-aspartate receptor (NMDAR) ion channels. One
      member of the conantokin family, conantokin (con)-G, a 17-residue peptide, is
      selective for NMDARs containing the N-methyl-d-aspartate receptor subunit 2 B
      (NR2B), whereas the homologous peptides, con-T and con-R, show broader
      selectivity for NR2 subunits. In this study, con-G, con-R, and con-T variants
      were chemically synthesized and employed to investigate their subunit
      selectivities as inhibitors of agonist-evoked ion currents in human embryonic
      kidney-293 (HEK-293) cells expressing various combinations of NMDAR subunits that
      contain NR1a or NR1b combined with NR2A or NR2B. Using truncation and point
      mutants, as well as chimeric conantokins, we determined that the N-terminus of
      con-G contains all the determinants for NR2B selectivity. With this information,
      a large number of (con) variants were synthesized and used to establish minimal
      sequence determinants for selectivity. Tyr at position 5 broadens the NR2
      selectivity, and recovery of NR2B selectivity in Tyr5 peptides was achieved by
      incorporating Ala or Gly at position 8. NR2B selectivity in con-R can be
      conferred through deletion of the Ala at position 10, thereby shifting the gamma
      carboxyglutamate (Gla) from position 11 to position 10, where a Gla naturally
      occurs in con-G and con-T. The nature of the amino acid at position 6 is also
      linked to subunit selectivity. Our studies suggest that the molecular
      determinants of conantokins that dictate NMDAR subunit selectivity are housed in
      specific residues of the N-termini of these peptides. Thus, it is possible to
      engineer desired NMDAR functional properties into conantokin-based peptides.

PMID- 20688136
TI  - Prenatal ethanol exposure attenuates GABAergic inhibition in basolateral amygdala
      leading to neuronal hyperexcitability and anxiety-like behavior of adult rat
      offspring.
AB  - Prenatal exposure to a relatively high-dose ethanol (EtOH) caused anxiety-like
      behavior of adult male rat offspring. Previous studies have demonstrated that
      GABA system in the basolateral amygdala complex (BLA) is involved in the
      pathogensis of anxiety-related disorders. The role of GABAergic system in the BLA
      was investigated in anxiety-like behavior evoked by prenatal EtOH exposure. The
      infusion of midazolam (MDZ), a positive modulator of GABA(A) receptor, into the
      BLA prevented anxiety-like behavior in EtOH-offspring without affecting the
      corresponding behavior of control offspring. The data suggest that anxiety-like
      behavior could be causally related to increased neuronal excitability
      attributable to depressed GABAergic inhibition in the BLA. To test this
      hypothesis, evoked potential was studied using brain slices from EtOH-offspring.
      Potential evoked in the BLA by single stimuli applied to external capsule showed
      multispike responses, indicative of GABAergic disinhibition. These multiple
      responses were no longer evident after the perfusion with MDZ. In the slices from
      EtOH-offspring, paired-pulse inhibition (GABA(A)-dependent) was suppressed. Also,
      in EtOH-offspring, long-term potentiation (LTP) was induced by a single train of
      high frequency stimulation, which did not induce LTP in control rats. Moreover,
      MDZ pretreatment prevented the facilitating effect of EtOH on LTP induction. The
      data provide the functional evidence that prenatal EtOH exposure attenuates
      GABAergic inhibition in the BLA resulting in neuronal hyperexcitability and
      anxiety-like behavior of adult rat offspring.

PMID- 20688138
TI  - Proteomic analysis of diaminochlorotriazine (DACT) adducts in three brain regions
      of Wistar rats.
AB  - Atrazine (ATRA) is the most commonly applied herbicide in the United States and
      is detected frequently in drinking water at significant levels. Following oral
      exposure, metabolism of ATRA generates diaminochlorotriazine (DACT), an
      electrophilic molecule capable of forming covalent protein adducts. At high
      doses, both ATRA and DACT can disrupt the preovulatory luteinizing hormone (LH)
      surge in rats, thereby altering normal reproductive function. This research was
      designed to identify DACT protein adducts formed in three distinct brain regions
      of ATRA-exposed rats, including the preoptic area (POA), medial basal
      hypothalamus (MBH), and cortex (CTX). Proteins with DACT adducts were identified
      following 2-dimensional electrophoresis (2-DE), immunodetection, and MALDI-TOF
      mass spectrometry analysis. Western blots from exposed animals revealed over 30
      DACT-modified spots that were absent in controls. Protein spots were matched to
      concurrently run 2-DE gels stained with Sypro Ruby, excised, and in-gel digested
      with trypsin.

PMID- 20688137
TI  - The neuregulin signaling pathway and schizophrenia: from genes to synapses and
      neural circuits.
AB  - Numerous genetic linkage and association studies implicate members of the
      Neuregulin-ErbB receptor (NRG-ErbB) signaling pathway as schizophrenia "at risk"
      genes. An emphasis of this review is to propose plausible neurobiological
      mechanisms, regulated by the Neuregulin-ErbB signaling network, that may be
      altered in schizophrenia and contribute to its etiology. To this end, the
      distinct neurotransmitter pathways, neuronal subtypes and neural network systems
      altered in schizophrenia are initially discussed. Next, the review focuses on the
      possible significance of genetic studies associating NRG1 and ErbB4 with
      schizophrenia, in light of the functional role of this signaling pathway in
      regulating glutamatergic, GABAergic and dopaminergic neurotransmission, as well
      as modulating synaptic plasticity and gamma oscillations. The importance of
      restricted ErbB4 receptor expression in GABAergic interneurons is emphasized,
      particularly their expression at glutamatergic synapses of parvalbumin-positive
      fast-spiking interneurons where modulation of inhibitory drive could account for
      the dramatic effects of NRG-ErbB signaling on gamma oscillations and pyramidal
      neuron output. A case is made for reasons that the NRG-ErbB signaling pathway
      constitutes a "biologically plausible" system for understanding the pathogenic
      mechanisms that may underlie the complex array of positive, negative and
      cognitive deficits associated with schizophrenia during development.

PMID- 20688139
TI  - 1H NMR-based metabonomic investigation of tributyl phosphate exposure in rats.
AB  - Tributyl phosphate (TBP) is a toxic organophosphorous compound widely used in
      many industrial applications, including significant usage in nuclear processing.
      The industrial application of this chemical is responsible for occupational
      exposure and environmental pollution. In this study, (1)H NMR-based metabonomics
      has been applied to investigate the metabolic response to TBP exposure. Male
      Sprague-Dawley rats were given a TBP-dose of 15 mg/kg body weight, followed by
      24h urine collection, as was previously demonstrated for finding most of the
      intermediates of TBP. High-resolution (1)H NMR spectroscopy of urine samples in
      conjunction with statistical pattern recognition and compound identification
      allowed for the metabolic changes associated with TBP treatment to be identified.
      Discerning NMR spectral regions corresponding to three TBP metabolites, dibutyl
      phosphate (DBP), N-acetyl-(S-3-hydroxybutyl)-L-cysteine and N-acetyl-(S-3
      oxobutyl)-L-cysteine, were identified in TBP-treated rats. In addition, the (1)H
      NMR spectra revealed TBP-induced variations of endogenous urinary metabolites
      including benzoate, urea, and trigonelline along with metabolites involved in the
      Krebs cycle including citrate, cis-aconitate, trans-aconitate, 2-oxoglutarate,
      succinate, and fumarate. These findings indicate that TBP induces a disturbance
      to the Krebs cycle energy metabolism and provides a biomarker signature of TBP
      exposure. We show that three metabolites of TBP, dibutylphosphate, N-acetyl-(S-3
      hydroxybutyl)-L-cysteine and N-acetyl-(S-3-oxobutyl)-L-cysteine, which are not
      present in the control groups, are the most important factors in separating the
      TBP and control groups (p<0.0023), while the endogenous compounds 2-oxoglutarate,
      benzoate, fumarate, trigonelline, and cis-aconetate were also important (p<0.01).

PMID- 20688140
TI  - Evaluation of ISCOM matrices clearance from rabbit nasal cavity by gamma
      scintigraphy.
AB  - Immune stimulating complexes and/or ISCOM matrices (adjuvant nanoparticles
      without antigen as a structural component) found potential applications as nasal
      vaccine adjuvant/delivery system owing to virus like particulate structure and
      saponin as potent Th1 adjuvant. One of important limiting factor for nasal
      vaccine delivery is the limited time available for absorption within the nasal
      cavity due to mucociliary clearance. In this report the clearance rate of ISCOM
      matrices from nasal cavity of rabbit was determined by gamma scintigraphy. ISCOM
      matrices were radiolabelled with (99m)Tc by direct labelling method using
      stannous chloride as a reducing agent. (99m)Tc labelled ISCOM matrices were
      administered into the nostril of female New Zealand rabbits and 1 min static
      views were repeated each 15 min until 4h. Clearance rate of ISCOM matrices from
      nasal cavity was calculated after applying the physical decay corrections. The
      mean labelling efficiency for ISCOM matrices were calculated as approximately
      58.4%. ISCOM matrices showed slower clearance rate compared to sodium
      pertechnetate control solution (p<0.005) from nasal cavity that may be due to
      particulate and hydrophobic characters of ISCOM particles even though it was also
      cleared within 4h from nasal cavity. Mucoadhesive ISCOM formulations that retain
      in nasal cavity for longer duration of time may reduce the dose/frequency of
      vaccine for nasal immunization.

PMID- 20688141
TI  - Preparation of pingyangmycin PLGA microspheres and related in vitro/in vivo
      studies.
AB  - Using a multiple emulsion solvent evaporation method, pingyangmycin was entrapped
      in poly(lactic-co-glycolic acid) (PLGA) to prepare a long-acting pingyangmycin
      PLGA microsphere formulation that can be sustainably released with high
      entrapment efficiency. Meanwhile, the effects of stirring speed during the
      multiple emulsion solvent evaporation process were also taken into consideration.
      Investigation of the in vitro release properties showed that the microsphere
      formulations could sustainably release the drug over nearly 28 d, and, moreover,
      it could stably control pingyangmycin release over nearly 24 d when
      intramuscularly injected into dogs. No serious toxic effect was observed in an
      acute toxicity test in mice. A subcutaneous xenotransplant model of hepatoma
      H(22) in mice was established for pharmacodynamic studies and the results showed
      that the process of preparing pingyangmycin PLGA microsphere formulations was
      feasible and that intramuscular injection of this microsphere formulation
      resulted in anti-tumor activity in vivo.

PMID- 20688142
TI  - Effect of Emblica officinalis (fruit) against UVB-induced photo-aging in human
      skin fibroblasts.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Emblica officinalis fruit (EO), commonly known as
      Amla is a reputed traditional medicine and functional food used in Indian
      subcontinent. It has long been used in Indian folk medicine to treat liver
      diseases, stomach ulcers, inflammatory diseases, metabolic disorders, geriatric
      complaints, skin disorders and beauty care. AIM OF THE STUDY: Recently, it has
      been shown to promote pro-collagen content and inhibit matrix metalloproteinase
      levels in skin fibroblast. The aim of the present study was to investigate the
      efficacy of EO to inhibit UVB-induced photo-aging in human skin fibroblasts.
      MATERIALS AND METHODS: Mitochondrial activity of human skin fibroblasts was
      measured by MTT-assay. Quantifications of pro-collagen 1 and matrix
      metalloproteinase 1 (MMP-1) release were performed by immunoassay techniques.
      Hyaluronidase inhibition assay was studied in vitro using bovine testicular
      hyaluronidase and human umbilical cord hyaluronic acid. Cell cycle analysis was
      performed by flowcytometry using propidium iodide. RESULTS: EO stimulated, the
      otherwise UVB inhibited cellular proliferation and protected pro-collagen 1
      against UVB-induced depletion via inhibition of UVB-induced MMP-1 in skin
      fibroblasts (10-40 MUg/mL, p>0.001). EO exhibited inhibitory activity of
      hyaluronidase (10-40 MUg/mL, p>0.001). Treatment with EO also prevented UVB
      disturbed cell cycle to normal phase. CONCLUSION: The results of the present
      study suggests that EO effectively inhibits UVB-induced photo-aging in human skin
      fibroblast via its strong ROS scavenging ability and its therapeutic and cosmetic
      applications remain to be explored.

PMID- 20688143
TI  - Sera from young and older humans equally sustain proliferation and
      differentiation of human myoblasts.
AB  - Using a human primary muscle cell culture model the behaviour of myoblasts
      (satellite cells) cultured in human serum obtained from either young or elderly
      individuals was studied. Serum was obtained from a total of 13 young (7 males and
      6 females aged, 23-36 years) and 9 elderly (4 males and 5 females aged 69-84
      years) subjects and used in a number of experiments. Myoblasts were extracted
      from human muscle biopsy samples taken from the vastus lateralis. In the first
      experiment myoblasts were isolated immediately after extraction from the biopsy
      in media containing human sera to examine its effects on the onset and
      progression of Ki67 and desmin expression. No effect of the age of the serum was
      observed at 3, 5 or 7 days of culture. In addition, cells were studied that had
      been expanded initially in optimum myoblast growth medium (GM, containing foetal
      calf serum and additional growth factors) prior to culture in medium containing
      15% human serum. The proportion of proliferating muscle cells coexpressing desmin
      and Ki67 antigens after 46 h was again similar in the young and old serum
      conditions. Culturing these myoblasts in media containing 2% human serum to study
      their fusion and differentiation also resulted in no difference between young and
      old serum conditions in terms of the percentage of nuclei inside myosin heavy
      chain positive myotubes. Despite the variability of different samples of
      myoblasts, the age of the serum donor has no effect on the expression of any
      measured index.

PMID- 20688144
TI  - Sustainable wastewater treatment: how might microbial fuel cells contribute.
AB  - The need for cost-effective low-energy wastewater treatment has never been
      greater. Clean water for our expanding and predominantly urban global population
      will be expensive to deliver, eats into our diminishing carbon-based energy
      reserves and consequently contributes to green house gases in the atmosphere and
      climate change. Thus every potential cost and energy cutting measure for
      wastewater treatment should be explored. Microbial fuel cells (MFCs) could
      potentially yield such savings but, to achieve this, requires significant
      advances in our understanding in a few critical areas and in our designs of the
      overall systems. Here we review the research which might accelerate our progress
      towards sustainable wastewater treatment using MFCs: system control and modelling
      and the understanding of the ecology of the microbial communities that catalyse
      the generation of electricity.

PMID- 20688145
TI  - Metabolic engineering of Escherichia coli and Corynebacterium glutamicum for the
      production of L-threonine.
AB  - L-threonine is an essential amino acid for mammals and as such has a wide and
      expanding application in industry with a fast growing market demand. The major
      method of production of l-threonine is microbial fermentation. To optimize L
      threonine production the fundamental solution is to develop robust microbial
      strains with high productivity and stability. Metabolic engineering provides an
      effective alternative to the random mutation for strain development. In this
      review, the updated information on genetics and molecular mechanisms for
      regulation of L-threonine pathways in Escherichia coli and Corynebacterium
      glutamicum are summarized, including L-threonine biosynthesis, intracellular
      consumption and trans-membrane export. Upon such knowledge, genetically defined L
      threonine producing strains have been successfully constructed, some of which
      have already achieved the productivity of industrial producing strains.
      Furthermore, strategies for strain construction are proposed and potential
      problems are identified and discussed. Finally, the outlook for future strategies
      to construct industrially advantageous strains with respect to recent advances in
      biology has been considered.

PMID- 20688146
TI  - Potentiating effect of morphine on oral Salmonella enterica serovar Typhimurium
      infection is MU-opioid receptor-dependent.
AB  - Previous studies from our laboratory demonstrated that mice treated with morphine
      pellets are sensitized to Salmonella enterica, serovar Typhimurium infection.
      However, the opioid receptor antagonist, naltrexone, only partially blocked the
      effect of morphine, raising the possibility that the opioid might have some of
      its effects through a nonopioid receptor. To further clarify whether
      sensitization to infection is an opioid receptor-dependent phenomenon, MU-opioid
      receptor knockout (MORKO) mice were used in the present study. Wild-type (WT) and
      MORKO mice were treated with morphine and their sensitivity to oral Salmonella
      infection was assessed by mortality, bacterial burdens in gut associated lymphoid
      tissue and in blood and peritoneal fluid, and by levels of pro-inflammatory
      cytokines in plasma. MORKO animals treated with morphine were refractory to a
      sublethal dose of Salmonella, while similar treatment of WT animals resulted in
      100% mortality. WT animals treated with morphine had high bacterial loads in all
      organs tested, while morphine-treated MORKO animals had no culturable Salmonella
      in any organs. Pro-inflammatory cytokine levels were elevated in morphine-treated
      WT but not MORKO mice infected with Salmonella. These results provide definitive
      evidence that the morphine-mediated enhancement of oral Salmonella infection is
      dependent on the MU-opioid receptor.

PMID- 20688147
TI  - Phototoxicity of essential oils intended for cosmetic use.
AB  - The aim of this study, linked-up with a previous study on bergamot oils, was the
      evaluation of phototoxic potential of essential oils (orange, lemon and Litsea
      cubeba), used as cosmetic ingredients. The applied tiered testing strategy
      included chemical analysis of the substances (by means of capillary gas
      chromatography/mass spectrometry), in vitro 3T3 NRU phototoxicity test and
      EpiDermTM skin phototoxicity test. In order to clarify the situation in man, the
      highest non-phototoxic/non-cytotoxic concentrations and concentrations 10 x lower
      (safety factor 10) were tested xin vivo by means of human skin photopatch test in
      a limited group of human volunteers. The study revealed, that phototoxicity of
      the essential oils was dependent on the content of photoactive components and the
      solvent used. The highest non-phototoxic concentrations obtained by the skin
      model assay proved to be a useful starting point for subsequent confirmatory
      human photopatch test aimed to identify safe concentration for human use.
      However, the highest non-phototoxic concentration obtained in the skin model
      assay cannot be applied directly for human practice (3 of 8 tested oils evoked a
      phototoxic reaction). A safety factor of 10 should be applied for extrapolation
      of experimental data from the skin model assay to man.

PMID- 20688148
TI  - In vitro reactivation of sarin-inhibited human acetylcholinesterase (AChE) by bis
      pyridinium oximes connected by xylene linkers.
AB  - A series of bis-pyridinium oximes connected by xylene linkers were synthesized
      and their in vitro reactivation potential was evaluated against human
      acetylcholinesterase (hAChE) inhibited by nerve agent sarin and the data were
      compared with 2-PAM and obidoxime. Among the synthesized compounds, N,N'-p-xylene
      bis-[(2,2'-hydroxyiminomethyl)pyridinium] dibromide (3c) was found to be the most
      potent reactivator for hAChE inhibited by sarin. The oxime 3c exhibited 45%
      regeneration of inhibited hAChE, in comparison to 34% and 24% regeneration by 2
      PAM and obidoxime, respectively, at a concentration of 10(-3) M within 10 min.
      The higher reactivation efficacies of these oximes were attributed to their acid
      dissociation constants (pKa). The pKa values of all the oximes were determined
      spectrophotometrically and correlated with their observed reactivation potential.
      This method involving the in vitro reactivation of inhibited hAChE may be useful
      for the screening of new oximes as reactivators.

PMID- 20688149
TI  - Riboflavin and photoproducts in MC3T3-E1 differentiation.
AB  - Photoderivatives of riboflavin can modulate the proliferation and survival of
      cancer cells. In this work, we examined the influence of riboflavin and
      photoderivatives on osteoblast differentiation induced by ascorbic acid and beta
      glycerophosphate. These compounds decreased the osteoblast proliferation,
      increased the alkaline phosphatase activity, promoted a reduction in matrix
      metalloproteinase-2 activity and the decreased in the OPG/RANKL ratio. The
      effects of flavins on osteoblasts were unrelated to the antioxidant activity of
      these compounds. The biological activity of osteogenic medium containing
      riboflavin and its photoderivatives involved the activation of different
      signaling pathways (AKT, FAK, CaMKII), caspases-3, -8 and -9, and up-regulation
      of the expression and/or stabilization of osteoblastic transcription factors
      (Runx2 and beta-catenin). These findings suggest a potential use of flavins as
      adjuvants to improve bone metabolism.

PMID- 20688150
TI  - The StrataTest(r) human skin model, a consistent in vitro alternative for
      toxicological testing.
AB  - Three-dimensional in vitro skin models provide an alternative to animal testing
      for assessing tissue damage caused by chemical or physical agents and for the
      identification and characterization of agents formulated to mitigate this damage.
      The StrataTest(r) human skin model made with pathogen-free NIKS(r) keratinocyte
      progenitors is a fully-stratified tissue containing epidermal and dermal
      components that possesses barrier function as determined by measurements of
      electrical impedance. Independent batches of skin tissues responded consistently
      to known chemical irritants even after refrigerated storage for up to 7 days.
      Reactive oxygen species (ROS) were detected after exposure of skin tissues to
      ozone, cigarette smoke or ultraviolet (UV) irradiation. Pretreatment with the
      antioxidant parthenolide-depleted (PD)-Feverfew extract prevented cigarette smoke
      induced or UV irradiation-mediated increases in ROS. Interleukin (IL)-1alpha and
      IL-1 receptor antagonist (IL-1RA) secretion increased in a dose dependent manner
      following UV irradiation but cytokine release was abrogated by pretreatment with
      a UVA/UVB sunscreen. Similarly, immunohistochemical detection showed increased
      thymidine dimer formation in UV-irradiated skin tissue that was prevented with
      sunscreen pretreatment. These results demonstrate that the StrataTest(r) human
      skin model is broadly applicable to a wide range of in vitro toxicological
      assays.

PMID- 20688151
TI  - Development of a versatile, target-oriented tiling microarray assay for measuring
      allele-specific gene expression.
AB  - In the study of gene expression, it is often desirable to distinguish transcript
      pools derived from different alleles present in the same organism. We report here
      an oligonucleotide tiling microarray designed to specifically target 518 single
      nucleotide polymorphisms (SNPs) between the two sequenced rice (Oryza sativa)
      subspecies indica and japonica. The tiling array included all 25-mer probes
      interrogating each SNP by placing the polymorphic site at all 25 possible
      positions within the probe. Through hybridization to a titration series in which
      the japonica- and indica-derived cDNA templates were mixed with altering
      proportions, a regression model was used to screen for diagnostic probe sets for
      each SNP. Our result indicates that 284 (55%) SNPs have at least one diagnostic
      probe pair suitable for distinguishing and quantifying the relative abundance of
      allele-specific transcripts. As a proof-of-concept, we analyzed allele-specific
      expression in reciprocal indica*japonica F(1) hybrids and detected imbalanced
      expression at approximately one third of the SNPs. These results were validated
      by RNA-sequencing and allele-specific real-time PCR experiments. Together, our
      work demonstrates the utility and advantages of the tiling array method in
      interrogating large numbers of SNPs for quantifying allele-specific gene
      expression.

PMID- 20688152
TI  - A comparison between ribo-minus RNA-sequencing and polyA-selected RNA-sequencing.
AB  - To compare the two RNA-sequencing protocols, ribo-minus RNA-sequencing (rmRNA
      seq) and polyA-selected RNA-sequencing (mRNA-seq), we acquired transcriptomic
      data-52 and 32 million alignable reads of 35 bases in length-from the mouse
      cerebrum, respectively. We found that a higher proportion, 44% and 25%, of the
      uniquely alignable rmRNA-seq reads, is in intergenic and intronic regions,
      respectively, as compared to 23% and 15% from the mRNA-seq dataset. Further
      analysis made an additional discovery of transcripts of protein-coding genes
      (such as Histone, Heg1, and Dux), ncRNAs, snoRNAs, snRNAs, and novel ncRNAs as
      well as repeat elements in rmRNA-seq dataset. This result suggests that rmRNA-seq
      method should detect more polyA- or bimorphic transcripts. Finally, through
      comparative analyses of gene expression profiles among multiple datasets, we
      demonstrated that different RNA sample preparations may result in significant
      variations in gene expression profiles.

PMID- 20688153
TI  - Transcriptional profiling of the injured sciatic nerve of mice carrying the
      Wld(S) mutant gene: identification of genes involved in neuroprotection,
      neuroinflammation, and nerve regeneration.
AB  - Wallerian degeneration (WD) involves the fragmentation of axonal segments
      disconnected from their cell bodies, segmentation of the myelin sheath, and
      removal of debris by Schwann cells and immune cells. The removal and
      downregulation of myelin-associated inhibitors of axonal regeneration and
      synthesis of growth factors by these two cell types are critical responses to
      successful nerve repair. Here, we analyzed the transcriptome of the sciatic nerve
      of mice carrying the Wallerian degeneration slow (Wld(S)) mutant gene, a gene
      that confers axonal protection in the distal stump after injury, therefore
      causing significant delays in WD, neuroinflammation, and axonal regeneration. Of
      the thousands of genes analyzed by microarray, 719 transcripts were
      differentially expressed between Wld(S) and wild-type (wt) mice. Notably, the
      Nmnat1, a transcript contained within the sequence of the Wld(S) gene, was
      upregulated by five to eightfold in the sciatic nerve of naive Wld(S) mice
      compared with wt. The injured sciatic nerve of wt could be further distinguished
      from the one of Wld(S) mice by the preferential upregulation of genes involved in
      axonal processes and plasticity (Chl1, Epha5, Gadd45b, Jun, Nav2, Nptx1, Nrcam,
      Ntm, Sema4f), inflammation and immunity (Arg1, Lgals3, Megf10, Panx1), growth
      factors/cytokines and their receptors (Clcf1, Fgf5, Gdnf, Gfralpha1, Il7r, Lif,
      Ngfr/p75(NTR), Shh), and cell adhesion and extracellular matrix (Adam8, Gpc1,
      Mmp9, Tnc). These results will help understand how the nervous and immune systems
      interact to modulate nerve repair, and identify the molecules that drive these
      responses.

PMID- 20688154
TI  - Comparison of phenotypic and genotypic antimicrobial profiles in Escherichia coli
      and Salmonella enterica from the same dairy cattle farms.
AB  - Transmission of antimicrobial drug resistance from resistant bacteria to non
      resistant strains is an important public health issue. In this study, we have
      examined the possibility of multiple resistance gene transfer between Escherichia
      coli and Salmonella in the natural setting. Bacteria isolated from calves
      concurrently shedding E. coli and Salmonella showed similar antimicrobial drug
      resistance patterns as measured by a broth dilution method. However, microarray
      analysis of the antibiotic resistance at the gene level revealed several
      differences in resistance gene profile. Resistance profiles of E. coli isolated
      from different farms were closer than the profile of E. coli and Salmonella
      isolated from the same farm. This shows that the chance of multiple resistance
      gene transfers between these species is unlikely.

PMID- 20688156
TI  - Pannexin channels in ATP release and beyond: an unexpected rendezvous at the
      endoplasmic reticulum.
AB  - The pannexin (Panx) family of proteins, which is co-expressed with connexins
      (Cxs) in vertebrates, was found to be a new GJ-forming protein family related to
      invertebrate innexins. During the past ten years, different studies showed that
      Panxs mainly form hemichannels in the plasma membrane and mediate paracrine
      signalling by providing a flux pathway for ions such as Ca2(+), for ATP and
      perhaps for other compounds, in response to physiological and pathological
      stimuli. Although the physiological role of Panxs as a hemichannel was
      questioned, there is increasing evidence that Panx play a role in vasodilatation,
      initiation of inflammatory responses, ischemic death of neurons, epilepsy and in
      tumor suppression. Moreover, it is intriguing that Panxs may also function at the
      endoplasmic reticulum (ER) as intracellular Ca2(+)-leak channel and may be
      involved in ER-related functions. Although the physiological significance and
      meaning of such Panx-regulated intracellular Ca2(+) leak requires further
      exploration, this functional property places Panx at the centre of many
      physiological and pathophysiological processes, given the fundamental role of
      intracellular Ca2(+) homeostasis and dynamics in a plethora of physiological
      processes. In this review, we therefore want to focus on Panx as channels at the
      plasma membrane and at the ER membranes with a particular emphasis on the
      potential implications of the latter in intracellular Ca2(+) signalling.

PMID- 20688155
TI  - Pulmonary vascular and cardiac effects of peroxynitrite decomposition in newborn
      rats.
AB  - Evidence implicates oxidative stress as playing a prominent role in the
      pathogenesis of pulmonary hypertension, to which peroxynitrite anion (ONOO(-))
      may make a major contribution. Hypothesizing that removal of ONOO(-) would
      attenuate chronic neonatal pulmonary hypertension, we examined the effects of a
      ONOO(-) decomposition catalyst (FeTPPS) on pulmonary arteries in vitro, on
      primary cultured pulmonary artery smooth muscle cell (PASMC) and cardiomyocyte
      survival and growth, and on central hemodynamics in rat pups exposed to hypoxia
      (13% O(2)) for 7 days from birth. Daily FeTPPS (30 mg/kg ip) reduced lung
      nitrotyrosine content, attenuated vascular remodeling, and normalized pulmonary
      vascular resistance in hypoxia-exposed animals. FeTPPS attenuated proliferation
      and increased apoptosis of neonatal PASMCs in vitro. Isolated neonatal pulmonary
      arteries treated with FeTPPS showed reduced agonist-induced force development and
      enhanced endothelium-dependent and -independent relaxation, possibly via
      increased nitrate. However, we observed endothelial dysfunction, enhanced lung
      tissue phosphodiesterase 5 activity, and biventricular cardiac hypertrophy in air
      exposed animals receiving FeTPPS. Further, in contrast to PASMCs, FeTPPS enhanced
      survival of newborn cardiomyocytes. We conclude that decomposition of ONOO(-)
      with FeTPPS attenuates chronic hypoxia-induced pulmonary hypertension; however,
      it may negatively influence the modulation of normal pulmonary arterial
      relaxation function, cell survival, and growth.

PMID- 20688157
TI  - Protein phosphatase 2A carboxymethylation and regulatory B subunits
      differentially regulate mast cell degranulation.
AB  - Asthma is characterised by antigen-mediated mast cell degranulation resulting in
      secretion of inflammatory mediators. Protein phosphatase 2A (PP2A) is a
      serine/threonine protein phosphatase composed of a catalytic (PP2A-C) subunit
      together with a core scaffold (PP2A-A) subunit and a variable, regulatory (PP2A
      B) subunit. Previous studies utilising pharmacological inhibition of protein
      phosphatases have suggested a positive regulatory role for PP2A in mast cell
      degranulation. In support of this we find that a high okadaic acid concentration
      (1MUM) inhibits mast cell degranulation. Strikingly, we now show that a low
      concentration of okadaic acid (0.1MUM) has the opposite effect, resulting in
      enhanced degranulation. Selective downregulation of the PP2A-Calpha subunit by
      short hairpin RNA also enhanced degranulation of RBL-2H3 mast cells, suggesting
      that the primary role of PP2A is to negatively regulate degranulation. PP2A-B
      subunits are responsible for substrate specificity, and carboxymethylation of the
      PP2A-C subunit alters B subunit binding. We show here that carboxymethylation of
      PP2A-C is dynamically altered during degranulation and inhibition of methylation
      decreases degranulation. Moreover downregulation of the PP2A-Balpha subunit
      resulted in decreased MK2 phosphorylation and degranulation, whilst
      downregulation of the PP2A-B'delta subunit enhanced p38 MAPK phosphorylation and
      degranulation. Taken together these data show that PP2A is both a positive and
      negative regulator of mast cell degranulation, and this differential role is
      regulated by carboxymethylation and specific PP2A-B subunit binding.

PMID- 20688158
TI  - Interaction between AR signalling and CRKL bypasses casodex inhibition in
      prostate cancer.
AB  - The underlying mechanism of failed androgen ablation therapy is unknown. It is
      recognised that under therapeutic conditions the androgen receptor (AR) remains
      functionally active independent of hormone stimulation and may function through
      an alternative pathway. We report a novel cooperative interaction between CRKL
      (an intracellular signalling adaptor protein) and the AR. We demonstrate by
      biochemical and genetic approaches that CRKL is associated with the AR complex
      and is localised in the nucleus of prostate cancer cells and patient tissue
      biopsies. The interaction between CRKL and the AR is functionally relevant as
      demonstrated by its presence on the enhancer region of an androgen regulated gene
      (human Kallikrein-2), its upregulation of PSA, and reduction in AR
      transactivation following its disruption by siRNA knockdown. In the presence of
      the AR inhibitor casodex, the expression of CRKL co-stimulated by growth factors
      is able to rescue AR activity independent of hormone. Our data provides insight
      on how a non-nuclear factor such as CRKL may interact with the AR complex to
      bypass hormone dependency by using an alternative growth factor signalling
      pathway in advanced prostate cancer.

PMID- 20688159
TI  - Akt isoform-specific inhibition of MDA-MB-231 cell proliferation.
AB  - To dissect the isoform-specific roles of Akt in breast cancer cells,
      constitutively active Akt isoforms were introduced into MDA-MB-231 cells. Both
      Akt1 and Akt2 efficiently inhibited the growth of MDA-MB-231 cells.
      Overexpression of Akt1 down-regulated ERK activity inhibiting Ser 259
      phosphorylation of c-Raf and subsequent downstream signaling. Akt2 overexpression
      up-regulated the cell cycle inhibitor p27. Cycloheximide decay assays showed that
      Akt2 increased the stability and nuclear localization of p27, thus inhibiting the
      cyclin E/CDK2 complex. These results suggest that the inhibition of cell
      proliferation by Akt1 and Akt2 is mediated by isoform-specific mechanisms.

PMID- 20688160
TI  - Pharmacokinetic evaluation of doxorubicin plasma levels in normal and overweight
      patients with breast cancer and simulation of dose adjustment by different
      indexes of body mass.
AB  - Although being used for decades in the treatment of several types of cancer,
      either alone or in association, only a few data about the pharmacokinetics of
      doxorubicin (DOX) in humans are available. DOX is frequently used in association
      with other anticancer drugs in the management of breast cancer. Pharmacokinetic
      data available in the literature show that after i.v. administration DOX follows
      a two-compartment open model, with a fast distribution phase followed by a very
      slow elimination phase. The objective of this work is to perform a pilot study in
      order to verify if the usual dose adjustment based on body surface area (BSA)
      would be producing the same plasma concentration-time profiles in patients with
      normal (<25) and above normal (>25) body mass index (BMI). In order to assess the
      pharmacokinetics of DOX after a short-term i.v. infusion of 60mg/m(2) of BSA, an
      experimental design using only five plasma samples of each patient was applied.
      Samples were collected at 0.00, 0.66 (right after the end of infusion), 1.66,
      8.66, and 24.66h. DOX pharmacokinetic profiles were evaluated after
      quantification of DOX using a new HPLC method developed and validated.
      Pharmacokinetic parameters (AUC(0-24.66) and C(max)) were analyzed by non
      compartmental and compartmental approaches. Significant differences (alpha=0.05)
      between overweight and normal weight groups were found with respect to AUC and
      C(max). After adjustment of dose by weight and by BMI, the compartmental model
      was used to simulate plasma concentrations and new values for C(max) and AUC(0
      24.66) were calculated. The new values obtained using both body weight (BW) and
      BMI were closer to the normal group than those obtained with BSA. According to
      the simulation, the differences of AUC and C(max) between the overweight group
      and the group of patients with normal weight were lower when the dose was
      adjusted by BW and BMI. These results suggest that more studies must be
      conducted, with more patients, in order to evaluate the best dose adjustment for
      DOX in women with breast cancer and overweight.

PMID- 20688161
TI  - Nano-structure of the laminin gamma-1 short arm reveals an extended and curved
      multidomain assembly.
AB  - Laminins are multidomain glycoproteins that play important roles in development
      and maintenance of the extracellular matrix via their numerous interactions with
      other proteins. Several receptors for the laminin short arms revealed their
      importance in network formation and intercellular signaling. However, both the
      detailed structure of the laminin gamma-1 short arm and its organization within
      the complexes is poorly understood due to the complexity of the molecule and the
      lack of a high-resolution structure. The presented data provide the first
      subatomic resolution structure for the laminin gamma-1 short arm in solution.
      This was achieved using an integrated approach that combined a number of
      complementary biophysical techniques such as small angle X-ray scattering (SAXS),
      analytical ultracentrifugation, dynamic light scattering and electron microscopy.
      As a result of this study, we have obtained a significantly improved model for
      the laminin gamma-1 short arm that represents a major step forward in molecular
      understanding of laminin-mediated complex formations.

PMID- 20688162
TI  - Leureptin: a soluble, extracellular leucine-rich repeat protein from Manduca
      sexta that binds lipopolysaccharide.
AB  - Leucine-rich repeat containing proteins are involved in immune response in many
      capacities. In insects, these include Toll-like receptors and the Anopheles
      gambiae proteins APL1 and LRIM1. Here we describe the identification and
      characterization of leureptin, a novel extracellular protein with 13 leucine-rich
      repeats from hemolymph of the insect Manduca sexta. After injection of bacteria,
      leureptin mRNA level increased in fat body, but protein levels in plasma
      decreased, an indication that leureptin is consumed during the immune response.
      Leureptin bound to bacterial lipopolysaccharide (LPS). Microscopy using leureptin
      antiserum showed that leureptin associates with hemocytes after injection of
      bacteria, an indication that leureptin is involved in hemocyte responses to
      bacterial infection. Sequence database searches suggest similar proteins are
      present in other Lepidopteran species.

PMID- 20688163
TI  - Arsenic trioxide combined with co-stimulatory molecule blockade prolongs survival
      of cardiac allografts in alloantigen-primed mice.
AB  - Various memory cell populations existing before organ transplantation are
      believed to be important barriers to extending the graft survival time. Here, we
      report that arsenic trioxide (As(2)O(3)), a common component of some Chinese
      traditional preparations, could obviously reduce the proliferation of splenic T
      cells in alloantigen-primed mice in vitro. Furthermore, we evaluated As(2)O(3)
      treatment alone or in combination with blocking monoclonal antibodies (mAb)
      against co-stimulatory molecules (LFA-1 and CD154) in the prevention of heart
      transplant rejection in alloantigen-primed mice. Alloantigen-primed mice were
      randomly divided into 4 groups of 6 animals each. The control group was given
      normal saline; the As(2)O(3) group received As(2)O(3) (5 mg/kg/d) (i.p.) on days
      0-10 post-transplantation; the Ab group received 100 MUg anti-LFA-1 mAb+250 MUg
      anti-CD154 mAb (i.p.) on the day of transplantation and 3 more times every
      alternate day and the As(2)O(3)+Ab group received a combined As(2)O(3) and Ab
      treatment protocol. The survival of the allografts was almost doubled among the
      As(2)O(3) group and Ab group compared with the control group (5, 5.6 vs 3.3
      days). A marked prolongation (16 days) of graft survival was achieved by the
      combination protocol compared with the control group (3.3 days; P<0.05). None of
      the treatment group showed side effects. Five days after transplantation, cardiac
      allografts, splenic T cells and serum were harvested for analysis. Compared with
      the control group, most of the treatment groups showed: (i) alleviation of
      allograft rejection in different levels; (ii) IFN-gamma expression was reduced
      and TGF-beta expression increased in both peripheral blood and within the grafts;
      (iii) the proportions of CD4(+) or CD8(+) memory T cells in the spleen of the
      recipients were significantly reduced while the expression of regulatory T cells
      (Tregs) was enhanced; (iv) the alloresponses of memory T cells were inhibited,
      and levels of alloantibodies in recipients' sera were also decreased. Among all
      these changes, the As(2)O(3)+Ab group showed the most significant changes. Our
      study highlights an obvious synergistic action of As(2)O(3) when combined with co
      stimulatory molecules blockade in prolonging the survival of cardiac allografts
      in alloantigen-primed mice.

PMID- 20688165
TI  - The dopamine transporter is differentially regulated after dopaminergic lesion.
AB  - The dopamine transporter (DAT) is a transmembrane glycoprotein responsible for
      dopamine (DA) uptake, which has been shown to be involved in DA-cell degeneration
      in Parkinson's disease (PD). At the same time, some studies suggest that DAT may
      be regulated in response to dopaminergic injury. We have investigated the
      mechanisms underlying DAT regulation after different degrees of dopaminergic
      lesion. DAT is persistently down-regulated in surviving midbrain DA-neurons after
      substantial (62%) loss of striatal DA-terminals, and transiently after slight
      (11%) loss of DA-terminals in rats. Transient DAT down-regulation consisted of a
      decrease of glycosylated (mature) DAT in the plasma membrane with accumulation of
      non-glycosylated (immature) DAT in the endoplasmic reticulum-Golgi (ERG)
      compartment, and recovery of the normal expression pattern 5 days after lesion.
      DAT redistribution to the ERG was also observed in HEK cells expressing rat DAT
      exposed to MPP(+), but not after exposure to DAT-unrelated neurotoxins. In
      contrast to other midbrain DA-cells, those in the ventrolateral region of the
      substantia nigra do not regulate DAT and degenerate shortly after slight DA
      lesion. These data suggest that DAT down-regulation is a post-translational event
      induced by DA-analogue toxins, consisting of a stop in its glycosylation and
      trafficking to the plasma membrane. Its persistence after substantial DA-lesion
      may act as a compensatory mechanism helping maintain striatal DA levels. The fact
      that neurons which do not regulate DAT die shortly after lesion suggests a
      relationship between DAT down-regulation and neuroprotection.

PMID- 20688166
TI  - Production of soluble, active acetyl serotonin methyl transferase in Leishmania
      tarentolae.
AB  - N-acetyl serotonin methyl transferase (ASMT) is the last enzyme in the melatonin
      synthesis pathway. Evidence linking autism-related disorders with disorders of
      melatonin metabolism, and, more specifically, with mutations of the gene encoding
      ASMT, prompted us to investigate the properties and localization of this enzyme.
      As a first step, we undertook to overproduce the protein in a recombinant host.
      Early attempts to produce ASMT in recombinant Escherichia coli yielded only
      insoluble and heavily degraded material. However, recombinant ASMT (rASMT) could
      be produced in soluble, active form and purified in milligram amounts when the
      gene was cloned and expressed in Leishmania tarentolae.

PMID- 20688168
TI  - ADP/ATP mitochondrial carrier MD simulations to shed light on the structural
      dynamical events that, after an additional mutation, restore the function in a
      pathological single mutant.
AB  - Molecular dynamics simulations of the wild type bovine ADP/ATP mitochondrial
      carrier, and of the single Ala113Pro and double Ala113Pro/Val180Met mutants,
      embedded in a lipid bilayer, have been carried out for 30ns to shed light on the
      structural-dynamical changes induced by the Val180Met mutation restoring the
      carrier function in the Ala113Pro pathologic mutant. Principal component analysis
      indicates that, for the three systems, the protein dynamics is mainly
      characterized by the motion of the matrix loops and of the odd-numbered helices
      having a conserved proline in their central region. Analysis of the motions shows
      a different behaviour of single pathological mutant with respect of the other two
      systems. The single mutation induces a regularization and rigidity of the H3
      helix, lost upon the introduction of the second mutation. This is directly
      correlated to the salt bridge distribution involving residues Arg79, Asp134 and
      Arg234, hypothesized to interact with the substrate. In fact, in the wild type
      simulation two stable inter-helices salt bridges, crucial for substrate binding,
      are present almost over all the simulation time. In line with the impaired ADP
      transport, one salt interaction is lost in the single mutant trajectory but
      reappears in the double mutant simulation, where a salt bridge network matching
      the wild type is restored. Other important structural-dynamical properties, such
      as the trans-membrane helices mobility, analyzed via the principal component
      analysis, are similar for the wild type and double mutant while are different for
      the single mutant, providing a mechanistic explanation for their different
      functional properties.

PMID- 20688167
TI  - The high-throughput protein sample production platform of the Northeast
      Structural Genomics Consortium.
AB  - We describe the core Protein Production Platform of the Northeast Structural
      Genomics Consortium (NESG) and outline the strategies used for producing high
      quality protein samples. The platform is centered on the cloning, expression and
      purification of 6X-His-tagged proteins using T7-based Escherichia coli systems.
      The 6X-His tag allows for similar purification procedures for most targets and
      implementation of high-throughput (HTP) parallel methods. In most cases, the 6X
      His-tagged proteins are sufficiently purified (>97% homogeneity) using a HTP two
      step purification protocol for most structural studies. Using this platform, the
      open reading frames of over 16,000 different targeted proteins (or domains) have
      been cloned as>26,000 constructs. Over the past 10 years, more than 16,000 of
      these expressed protein, and more than 4400 proteins (or domains) have been
      purified to homogeneity in tens of milligram quantities (see Summary Statistics,
      http://nesg.org/statistics.html). Using these samples, the NESG has deposited
      more than 900 new protein structures to the Protein Data Bank (PDB). The methods
      described here are effective in producing eukaryotic and prokaryotic protein
      samples in E. coli. This paper summarizes some of the updates made to the protein
      production pipeline in the last 5 years, corresponding to phase 2 of the NIGMS
      Protein Structure Initiative (PSI-2) project. The NESG Protein Production
      Platform is suitable for implementation in a large individual laboratory or by a
      small group of collaborating investigators. These advanced automated and/or
      parallel cloning, expression, purification, and biophysical screening
      technologies are of broad value to the structural biology, functional proteomics,
      and structural genomics communities.

PMID- 20688164
TI  - Cerebral cortex structure in prodromal Huntington disease.
AB  - Neuroimaging studies of subjects who are gene-expanded for Huntington Disease,
      but not yet diagnosed (termed prodromal HD), report that the cortex is "spared,"
      despite the decrement in striatal and cerebral white-matter volume. Measurement
      of whole-cortex volume can mask more subtle, but potentially clinically relevant
      regional changes in volume, thinning, or surface area. The current study
      addressed this limitation by evaluating cortical morphology of 523 prodromal HD
      subjects. Participants included 693 individuals enrolled in the PREDICT-HD
      protocol. Of these participants, 523 carried the HD gene mutation (prodromal HD
      group); the remaining 170 were non gene-expanded and served as the comparison
      group. Based on age and CAG repeat length, gene-expanded subjects were
      categorized as "Far from onset," "Midway to onset," "Near onset," and "already
      diagnosed." MRI scans were processed using FreeSurfer. Cortical volume,
      thickness, and surface area were not significantly different between the Far from
      onset group and controls. However, beginning in the Midway to onset group, the
      cortex showed significant volume decrement, affecting most the posterior and
      superior cerebral regions. This pattern progressed when evaluating the groups
      further into the disease process. Areas that remained mostly unaffected included
      ventral and medial regions of the frontal and temporal cortex. Morphologic
      changes were mostly in thinning as surface area did not substantially change in
      most regions. Early in the course of HD, the cortex shows changes that are
      manifest as cortical thinning and are most robust in the posterior and superior
      regions of the cerebrum.

PMID- 20688169
TI  - cDNA cloning of the immunoglobulin heavy chain genes in banded houndshark Triakis
      scyllium.
AB  - In this study, cDNAs encoding the secreted forms of the immunoglobulin (Ig) heavy
      chains of IgM, IgNAR, and IgW were cloned from the banded houndshark Triakis
      scyllium. Two clones for the IgM heavy chains encoded 569 and 570 amino acids,
      whose conserved (C) region showed 47-70% amino acid identities to those reported
      in other cartilaginous fish. Four clones for the IgNAR encoded 673-670 amino
      acids with conserved Ig-superfamily domains. The IgNAR C region showed 56-69%
      amino acid identities to those so far reported. High-throughput sequencing
      revealed that in most of the IgNAR sequences, the two variable regions (CDR1 and
      CDR3) each possess a cysteine residue. Three types of IgW were identified; one
      contained Ig-superfamily domains that are in other cartilaginous fish, one lacks
      the 3rd domain in the constant region, and one lacks the 3rd to 5th domains.
      Despite these differences, the IgW isoforms clustered with IgWs of other
      cartilaginous fishes and the C regions showed 47-89% amino acid identities. mRNAs
      for IgM and IgNAR were detected in various tissues, while IgW mRNA was mainly
      detected in pancreas. The banded hounded shark also has IgM, IgW and IgNAR as
      well as the other cartilaginous fish with unique IgW isoform.

PMID- 20688170
TI  - Effect of probiotics enriched diet on Paralichthys olivaceus infected with
      lymphocystis disease virus (LCDV).
AB  - We report the effect of two probiotics, Lactobacil and Sporolac as separate or
      mixed diets on innate immune mechanisms, such as phagocytosis activity,
      superoxide anion production of blood leukocytes, complement activity and plasma
      lysozyme activity, and disease resistance in lymphocystis disease virus (LCDV)
      infected olive flounder, Paralichthys olivaceus (523.5 +/- 18.3 g) on week 1, 2,
      and 4. In infected fish, administration of diet supplemented with Lactobacil
      individually or mixed with Sporolac significantly enhanced the immune parameters
      like phagocytic activity superoxide anion production, complement activity, and
      plasma lysozyme. However administration of supplemented diet with Sporolac alone,
      all the chosen immune parameters did not enhance when compared to control group;
      this diets resulted in lower mortality (30% and 25%) than Sporolac diet group
      (45%) in 30 days. We conclude that Lactobacil individually or mixed with Sporolac
      act as immunostimulants that enhance the innate immune response and disease
      resistance in lymphocystis disease virus (LCDV) infected olive flounder.

PMID- 20688171
TI  - Immune enhancement of chemotherapeutants on lymphocystis disease virus (LDV)
      infected Paralichthys olivaceus.
AB  - In olive flounder, Paralichthys olivaceus infected with lymphocystis disease
      virus (LDV) bath treatment with formalin, hydrogen peroxide or Jenoclean at 50,
      100, and 200 ppm daily 10 min for 60 days enhanced the innate immune response and
      disease resistance. Jenoclean enhanced the immune parameters at the lowest
      concentration of 50 ppm; on the other hand, hydrogen peroxide bath treatment
      enhanced the immunity level at 100 ppm, while formalin was effective only at 200
      ppm. A low cumulative mortality and high relative percent survival was noted in
      Jenoclean treated group followed by formalin and hydrogen peroxide treated
      groups. In olive flounder at low concentrations of 50 ppm or 100 ppm hydrogen
      peroxide and Jenoclean effectively prevent LDV infection.

PMID- 20688172
TI  - Differential gene expression profile of the hepatopancreas of white spot syndrome
      virus infected Fenneropenaeus indicus by suppression subtractive hybridization.
AB  - Suppression Subtractive Hybridization was employed in order to identify the
      differentially expressed genes in the hepatopancreas of white spot syndrome virus
      infected Fenneropenaeus indicus. A forward subtracted cDNA library generated 356
      clones following a white spot syndrome virus infection. A total of 345 clones
      with more than 100 nucleotides were selected for further analysis using
      bioinformatics tools after vector screening. Twenty-three contigs and 111
      singletons were generated from a total of 134 consensuses. The consensuses, on a
      sequence homology search using BLASTX (NCBI), revealed that 74 (55%) of them had
      no significant match to reported sequences in the database, suggesting that they
      were found for the first time and are probably associated with shrimp immune
      function. Out of the remaining 60 (45%) consensuses, 43 had significant homology
      to known protein sequences in the database while 17 consensuses are homologous to
      unknown proteins in the database which are considered novel. The most abundant
      genes in the subtracted library were antimicrobial peptides accounting for 56
      clones; among which one is a member of SNF2 family of proteins and another
      belonged to PfP1 family of proteins on analysis using Antimicrobial peptide
      predictor software. The other predicted genes in the subtracted library include
      signal transduction molecules (GTPase, Serine threonine kinase, Armadillo repeats
      etc), antioxidant enzymes (Cytochrome oxidase, Monomeric sarcosine oxidase and
      Catalase), active transporters (Nuclear Localization Signal [NLS], calcium
      ATPase, sodium glutamate symporter, Store-Operated Calcium Entry [SOCE] and
      ribonucleoprotein [RNP]) contributing to 19, 14 and 5 clones respectively. Three
      clones are homologous to reverse transcriptase; a first time report in shrimp and
      one each belong to cell adhesion molecule and Proteinase. InterProScan at EMBL,
      when used for an integrated search at PROSITE predicted; signal sequences and
      transmembrane regions for 13 clones. This is the first report on the differential
      gene expression in WSSV-infected F. indicus. The high expression of immune
      related genes in response to virus infection in shrimp will provide a new insight
      into the crustacean innate immunity. Further work on the functionality of the
      unknown genes in shrimps will give an overview on the role of the differentially
      expressed genes during viral infection and increase our understanding for
      developing antiviral measures by making use of the shrimp defense mechanism.

PMID- 20688173
TI  - BRICHOS domain-containing leukocyte cell-derived chemotaxin 1-like cDNA from disk
      abalone Haliotis discus discus.
AB  - A BRICHOS domain-containing leukocyte cell-derived chemotaxin 1-like cDNA was
      cloned from the disk abalone (Haliotis discus discus) and designated as AbLECT-1.
      A full-length (705 bp) of AbLECT-1 cDNA was composed of a 576 bp open reading
      frame that translates into a putative peptide of 192 amino acids. Deduced amino
      acid sequence of AbLECT-1 had 15.5- and 27.8% identity and similarity to human
      LECT-1, respectively. Quantitative real-time PCR analysis results showed that the
      mRNA of AbLECT-1 was constitutively expressed in abalone hemocytes, gills,
      mantle, muscle, digestive tract and hepatopancreas in a tissue-specific manner.
      Moreover, the AbLECT-1 transcription level was induced in hemocytes after
      challenge with Vibrio alginolyticus, Vibrio parahemolyticus, and Listeria
      monocytogenes suggesting that it may be involved in immune response reactions in
      abalone.

PMID- 20688174
TI  - Potential fMRI correlates of 40-Hz phase locking in primary auditory cortex,
      thalamus and midbrain.
AB  - MEG and BOLD fMRI are both related to post-synaptic activity, but not all
      components of the MEG appear to be equally reflected by the BOLD response. To
      evaluate potential BOLD correlates of the auditory 40-Hz steady-state response
      (SSR), 40-Hz amplitude-modulated (AM) tones and pure-tones with 1000-Hz tone
      frequency and 32-s tone duration were presented to 12 listeners in fMRI and MEG.
      The SSR evoked by AM-tones is readily separated from the onset, offset and
      sustained fields in MEG by a high-pass filter. For fMRI, a contrast of AM- versus
      pure-tones was used to estimate activity related more specifically to the 40-Hz
      SSR, but excluding other activity that is evoked by AM and pure-tones alike. This
      contrast showed sustained BOLD activation confined to the medial part of Heschl's
      gyrus, the location of the primary auditory cortex, as well as activity in the
      medial geniculate body (MGB) and the inferior colliculus (IC). Transient BOLD
      onset and offset responses were prominent throughout the auditory cortex. In
      contrast, sustained BOLD activity for pure-tones was weak and did not match well
      with the time course of the sustained field, suggesting that there is no reliable
      BOLD correlate of the sustained field in MEG. The sustained BOLD activity in
      primary auditory cortex is therefore more likely linked to the phase-locked SSR.
      Enhanced BOLD for AM compared to pure-tones in the IC and MGB may similarly be
      related to phase locking.

PMID- 20688175
TI  - How to test for dual-task-specific effects in brain imaging studies--an
      evaluation of potential analysis methods.
AB  - The study of the concurrent performance of two tasks allows deep insights into
      the human cognitive system and, accordingly, an increasing number of brain
      imaging studies are conducted to identify the neuroanatomical correlates of such
      dual-task performance. In this overview we present currently used approaches to
      identify dual-task-specific activations in fMRI and PET studies. A comparison is
      made in order to identify the approaches which have the potential to validly
      detect dual-task-specific activation patterns, i.e. activation which cannot be
      explained by the individual performance of the component tasks alone. We
      demonstrate that while all approaches suffer from at least some drawbacks, the
      best (although potentially over-conservative) approach is to compare the dual
      task with the sum of the single tasks, the second-best is an interaction
      contrast, and the third-best a conjunction analysis. Comparisons of the dual task
      with the mean of single-task activity or with only one single task should be
      avoided except for a few specific situations. We generalize our conclusions to
      related research areas, such as multisensory integration or divided attention.

PMID- 20688176
TI  - Anatomical differences and network characteristics underlying smoking cue
      reactivity.
AB  - A distributed network of brain regions is linked to drug-related cue responding.
      However, the relationships between smoking cue-induced phasic activity and
      possible underlying differences in brain structure, tonic neuronal activity and
      connectivity between these brain areas are as yet unclear. Twenty-two smokers and
      22 controls viewed smoking-related and neutral pictures during a functional
      arterial spin labeling scanning session. T1, resting functional, and diffusion
      tensor imaging data were also collected. Six brain areas, dorsal lateral
      prefrontal cortex (dlPFC), dorsal medial prefrontal cortex (dmPFC), dorsal
      anterior cingulate cortex/cingulate cortex, rostral anterior cingulate cortex
      (rACC), occipital cortex, and insula/operculum, showed significant smoking cue
      elicited activity in smokers when compared with controls and were subjected to
      secondary analysis for resting state functional connectivity (rsFC), structural,
      and tonic neuronal activity. rsFC strength between rACC and dlPFC was positively
      correlated with the cue-elicited activity in dlPFC. Similarly, rsFC strength
      between dlPFC and dmPFC was positively correlated with the cue-elicited activity
      in dmPFC while rsFC strength between dmPFC and insula/operculum was negatively
      correlated with the cue-elicited activity in both dmPFC and insula/operculum,
      suggesting these brain circuits may facilitate the response to the salient
      smoking cues. Further, the gray matter density in dlPFC was decreased in smokers
      and correlated with cue-elicited activity in the same brain area, suggesting a
      neurobiological mechanism for the impaired cognitive control associated with drug
      use. Taken together, these results begin to address the underlying neurobiology
      of smoking cue salience, and may speak to novel treatment strategies and targets
      for therapeutic interventions.

PMID- 20688177
TI  - Hemisphere- and gender-related differences in small-world brain networks: a
      resting-state functional MRI study.
AB  - We employed resting-state functional MRI (R-fMRI) to investigate hemisphere- and
      gender-related differences in the topological organization of human brain
      functional networks. Brain networks were first constructed by measuring inter
      regional temporal correlations of R-fMRI data within each hemisphere in 86 young,
      healthy, right-handed adults (38 males and 48 females) followed by a graph-theory
      analysis. The hemispheric networks exhibit small-world attributes (high
      clustering and short paths) that are compatible with previous results in the
      whole-brain functional networks. Furthermore, we found that compared with
      females, males have a higher normalized clustering coefficient in the right
      hemispheric network but a lower clustering coefficient in the left hemispheric
      network, suggesting a gender-hemisphere interaction. Moreover, we observed
      significant hemisphere-related differences in the regional nodal characteristics
      in various brain regions, such as the frontal and occipital regions (leftward
      asymmetry) and the temporal regions (rightward asymmetry), findings that are
      consistent with previous studies of brain structural and functional asymmetries.
      Together, our results suggest that the topological organization of human brain
      functional networks is associated with gender and hemispheres, and they provide
      insights into the understanding of functional substrates underlying individual
      differences in behaviors and cognition.

PMID- 20688179
TI  - Effects of selection and mutation on mitochondrial variation and inferences of
      historical population expansion in a Caribbean reef fish.
AB  - Mitochondrial sequence data has contributed to the understanding of historical
      demography through the application of neutrality tests and coalescent estimators
      of population growth rates. Characteristics of the mitochondrial genome, such as
      high mutation rate and lack of recombination, render it particularly suitable for
      these types of studies. However, selection can also affect patterns of
      mitochondrial variation. Furthermore, conclusions based on single mitochondrial
      loci can be sensitive to differences among mitochondrial genes in mutation rate
      and pattern and levels of homoplasy. We tested the contributions of these factors
      to patterns of mitochondrial variation in the Caribbean reef fish Halichoeres
      bivittatus using a multilocus sequence-based approach. Mitochondrial protein
      coding loci deviated strongly from a neutral model of evolution and indicated
      high rates of estimated population growth. In contrast, the mitochondrial control
      region and a nuclear intron showed little or no deviation from neutrality and low
      estimated growth rates. The level of variation among loci is inconsistent with a
      demographic explanation and likely stems from the influence of mutation and
      selection on the mitochondrial genome. In H. bivittatus, a finding of high rates
      of population growth is likely an artifact of selection on mitochondrial
      proteins. This result suggests caution in the interpretation of variation at
      single mitochondrial loci, and highlights the importance of the use of unlinked
      nuclear loci to test demographic inferences made from mitochondrial DNA.

PMID- 20688180
TI  - Does dispersal across an aquatic geographic barrier obscure phylogeographic
      structure in the diamond-backed watersnake (Nerodia rhombifer)?
AB  - The impact of barriers to dispersal and gene flow is often inferred to be the
      primary cause of lineage divergence and phylogeographic structure in terrestrial
      organisms. In particular, the Mississippi River has been implicated as a barrier
      to gene flow in many species, including aquatic taxa. However, if barriers are
      permeable to organisms, then phylogeographic structure may be difficult to detect
      due to gene flow between lineages. Using time-calibrated Bayesian phylogenetic
      analyses of mtDNA, and phylogeographic coalescent simulations, we determine if
      the Mississippi River operates as a barrier to gene flow in the aquatic diamond
      backed watersnake (Nerodia rhombifer). The phylogenetic analyses support a basal
      division within N. rhombifer mtDNA lineages that coincides with populations
      generally east and west of the Mississippi River. These results, and that of the
      divergence dating analyses, therefore suggest that the river was a significant
      barrier to gene flow in the Pleistocene ~ 1.4 million years ago, presumably
      during an interglacial period when the river was much wider. However, we also
      detect western haplotypes in the eastern clade, and vice versa, thereby
      indicating that this barrier has not been complete. Nonetheless, the coalescent
      simulations that account for limited migration suggest that the Mississippi River
      was an important feature that shaped the phylogeographic history of this aquatic
      snake in the USA despite limited gene flow.

PMID- 20688181
TI  - Donor serostatus has an impact on cytomegalovirus-specific immunity,
      cytomegaloviral disease incidence, and survival in seropositive hematopoietic
      cell transplant recipients.
AB  - More cytomegalovirus (CMV)-specific T cells are transferred with grafts from CMV
      seropositive than seronegative donors. We hypothesized that seropositive
      recipients of grafts from seropositive donors (D+R+) have higher counts of CMV
      specific T cells than seropositive recipients of grafts from seronegative donors
      (D-R+), and that this is clinically relevant in the setting of in vivo T cell
      depletion using rabbit-antihuman thymocyte globulin (ATG). We reviewed charts of
      298 ATG-conditioned, seropositive recipients for CMV reactivation (pp65
      antigenemia or CMV DNAemia above institutional threshold for preemptive therapy),
      recurrent CMV reactivation, CMV disease, and death. In 77 of these patients, we
      enumerated CMV-specific T cells. Median follow-up was 564 days. CMV-specific CD4+
      and, to a lesser degree, CD8+ T cell counts were higher in D+R+ than D-R+
      patients. D+R+ patients had lower cumulative incidence of CMV reactivation (21%
      versus 48%, P < .001), recurrent reactivation (4% versus 15%, P = .003), CMV
      disease (3% versus 13%, P = .005) and mortality (42% versus 56%, P = .006). We
      conclude that in the setting of in vivo T cell depletion using ATG, seropositive
      donors should be used for seropositive recipients. For scenarios where only
      seronegative donors are available, strategies to improve CMV-specific immunity
      (e.g., donor vaccination) should be explored.

PMID- 20688182
TI  - D-index and Prediction of Infection.

PMID- 20688183
TI  - Lissencephaly: mechanistic insights from animal models and potential therapeutic
      strategies.
AB  - Lissencephaly is a severe human neuronal migration defect characterized by a
      smooth cerebral surface, mental retardation and seizures. The two most common
      genes mutated in patients with lissencephaly are LIS1 and DCX. LIS1 was the first
      gene cloned that was important for neuronal migration in any organism, and
      heterozygous mutations or deletions of LIS1 are found in the majority of patients
      with lissencephaly, while DCX mutations were found in males with X-linked
      lissencephaly. In this review, we will discuss how an understanding of the
      molecular and cellular pathways disrupted in model organisms with Lis1 and Dcx
      mutations or knock-down not only provide insights into the normal processes of
      neuronal migration, including neurogenesis, but they also may lead to potential
      novel therapeutic strategies for these severe cortical malformations.

PMID- 20688185
TI  - Glutamine protects ischemia-reperfusion induced acute lung injury in isolated rat
      lungs.
AB  - Glutamine has been used to treat a number of diseases via modulating the
      inflammatory response. The purpose of this study is to investigate whether
      glutamine has a beneficial effect in ischemia-reperfusion (IR) induced acute lung
      injury in an isolated rat lung model. Typical acute lung injury in rats was
      successfully induced by 60 min of ischemia and 60 min of reperfusion. At the end
      of experiment, bronchoalveolar lavage fluid (BALF), perfusate and lung tissues
      were collected to evaluate the degree of lung injury. Glutamine (20 mM) was
      administrated before ischemia or after ischemia. IR caused a significant increase
      in the capillary filtration coefficient; lung weight gain; lung weight to body
      weight ratio; wet to dry weight ratio; pulmonary arterial pressure; and protein
      concentration and lactate dehydrogenase level in BALF. Tumor necrosis factor
      alpha and cytokine induced neutrophil chemoattractant-1 in perfusate, and
      malondialdehyde levels, carbonyl content and myeloperoxidase activities in lung
      tissue were also significantly increased. In addition, the lung tissues showed
      increased septal thickness and neutrophil infiltration. Furthermore, NF-kappaB
      activity and degradation of IkappaB-alpha were significantly increased in the
      lungs. Treatment with glutamine before ischemia or after ischemia significantly
      decreased the increase in these parameters. Our study showed that glutamine
      treatment decreased IR-induced acute lung injury. The protective mechanism may be
      due to the inhibition of NF-kappaB activation and the attenuation of oxidative
      stress.

PMID- 20688184
TI  - Pancreatic beta-cells: from generation to regeneration.
AB  - The pancreas is composed of two main compartments consisting of endocrine and
      exocrine tissues. The majority of the organ is exocrine and responsible for the
      synthesis of digestive enzymes and for their transport via an intricate ductal
      system into the duodenum. The endocrine tissue represents less than 2% of the
      organ and is organized into functional units called islets of Langerhans,
      comprising alpha-, beta-, delta-, epsilon- and PP-cells, producing the hormones
      glucagon, insulin, somatostatin, ghrelin and pancreatic polypeptide (PP),
      respectively. Insulin-producing beta-cells play a central role in the control of
      the glucose homeostasis. Accordingly, absolute or relative deficiency in beta
      cells may ultimately lead to type 1 and/or type 2 diabetes, respectively. One
      major goal of diabetes research is therefore to understand the molecular
      mechanisms controlling the development of beta-cells during pancreas
      morphogenesis, but also those underlying the regeneration of adult injured
      pancreas, and assess their significance for future cell-based therapy. In this
      review, we will therefore present new insights into beta-cell development with
      focus on beta-cell regeneration.

PMID- 20688186
TI  - Engineering of biotin-prototrophy in Pichia pastoris for robust production
      processes.
AB  - Biotin plays an essential role as cofactor for biotin-dependent carboxylases
      involved in essential metabolic pathways. The cultivation of Pichia pastoris, a
      methylotrophic yeast that is successfully used as host for the production of
      recombinant proteins, requires addition of high dosage of biotin. As biotin is
      the only non-salt media component used during P. pastoris fermentation (apart
      from the carbon source), nonconformities during protein production processes are
      usually attributed to poor quality of the added biotin. In order to avoid
      dismissed production runs due to biotin quality issues, we engineered the biotin
      requiring yeast P. pastoris to become a biotin-prototrophic yeast. Integration of
      four genes involved in the biotin biosynthesis from brewing yeast into the P.
      pastoris genome rendered P. pastoris biotin-prototrophic. The engineered strain
      has successfully been used as production host for both intracellular and secreted
      heterologous proteins in fed-batch processes, employing mineral media without
      vitamins. Another field of application for these truly prototrophic hosts is the
      production of biochemicals and small metabolites, where defined mineral media
      leads to easier purification procedures.

PMID- 20688187
TI  - Cardiac arrhythmia and thyroid dysfunction: a novel genetic link.
AB  - Inherited Long QT Syndrome (LQTS), a cardiac arrhythmia that predisposes to the
      often lethal ventricular fibrillation, is commonly linked to mutations in KCNQ1.
      The KCNQ1 voltage-gated K(+) channel alpha subunit passes ventricular myocyte
      K(+) current that helps bring a timely end to each heart-beat. KCNQ1, like many
      K(+) channel alpha subunits, is regulated by KCNE beta subunits, inherited
      mutations in which also associate with LQTS. KCNQ1 and KCNE mutations are also
      associated with atrial fibrillation. It has long been known that thyroid status
      strongly influences cardiac function, and that thyroid dysfunction causes
      abnormal cardiac structure and rhythm. We recently discovered that KCNQ1 and
      KCNE2 form a thyroid-stimulating hormone-stimulated K(+) channel in the thyroid
      that is required for normal thyroid hormone biosynthesis. Here, we review this
      novel genetic link between cardiac and thyroid physiology and pathology, and its
      potential influence upon future therapeutic strategies in cardiac and thyroid
      disease.

PMID- 20688188
TI  - Trypanosome alternative oxidase, a potential therapeutic target for sleeping
      sickness, is conserved among Trypanosoma brucei subspecies.
AB  - Trypanosoma brucei rhodesiense and T. b. gambiense are known causes of human
      African trypanosomiasis (HAT), or "sleeping sickness," which is deadly if
      untreated. We previously reported that a specific inhibitor of trypanosome
      alternative oxidase (TAO), ascofuranone, quickly kills African trypanosomes in
      vitro and cures mice infected with another subspecies, non-human infective T. b.
      brucei, in in vivo trials. As an essential factor for trypanosome survival, TAO
      is a promising drug target due to the absence of alternative oxidases in the
      mammalian host. This study found TAO expression in HAT-causing trypanosomes; its
      amino acid sequence was identical to that in non-human infective T. b. brucei.
      The biochemical understanding of the TAO including its 3 dimensional structure
      and inhibitory compounds against TAO could therefore be applied to all three T.
      brucei subspecies in search of a cure for HAT. Our in vitro study using T. b.
      rhodesiense confirmed the effectiveness of ascofuranone (IC(50) value: 1 nM) to
      eliminate trypanosomes in human infective strain cultures.

PMID- 20688190
TI  - Facilitating pre-operative assessment guidelines representation using SNOMED CT.
AB  - OBJECTIVE: To investigate whether SNOMED CT covers the terms used in pre
      operative assessment guidelines, and if necessary, how the measured content
      coverage can be improved. METHODS: Pre-operative assessment guidelines were
      retrieved from the websites of (inter)national anesthesia-related societies. The
      recommendations in the guidelines were rewritten to "IF condition THEN action"
      statements to facilitate data extraction. Terms were extracted from the IF-THEN
      statements and mapped to SNOMED CT. Content coverage was measured by using three
      scores: no match, partial match and complete match. Non-covered concepts were
      evaluated against the SNOMED CT editorial documentation. RESULTS: From 6
      guidelines, 133 terms were extracted, of which 71% (n=94) completely matched with
      SNOMED CT concepts. Disregarding the vague concepts in the included guidelines
      SNOMED CT's content coverage was 89%. Of the 39 non-completely covered concepts,
      69% violated at least one of SNOMED CT's editorial principles or rules. These
      concepts were categorized based on four categories: non-reproducibility,
      classification-derived phrases, numeric ranges, and procedures categorized by
      complexity. CONCLUSION: Guidelines include vague terms that cannot be well
      supported by terminological systems thereby hampering guideline-based decision
      support systems. This vagueness reduces the content coverage of SNOMED CT in
      representing concepts used in the pre-operative assessment guidelines.
      Formalization of the guidelines using SNOMED CT is feasible but to optimize this,
      first the vagueness of some guideline concepts should be resolved and a few
      currently missing but relevant concepts should be added to SNOMED CT.

PMID- 20688189
TI  - High-content imaging for automated determination of host-cell infection rate by
      the intracellular parasite Trypanosoma cruzi.
AB  - Chagas disease affects 8-11 million people, mostly in Latin America. Sequelae
      include cardiac, peripheral nervous and/or gastrointestinal disorders, thus
      placing a large economic and social burden on endemic countries. The pathogenesis
      and the evolutive pattern of the disease are not fully clarified. Moreover,
      available drugs are partially effective and toxic, and there is no vaccine.
      Therefore, there is an urgent need to speed up basic and translational research
      in the field. Here, we applied automated high-content imaging to generate
      multiparametric data on a cell-by-cell basis to precisely and quickly determine
      several parameters associated with in vitro infection of host cell by Trypanosoma
      cruzi, the causative agent of Chagas disease. Automated and manual
      quantifications were used to determine the percentage of T. cruzi-infected cells
      in a 96-well microplate format and the data generated was statistically
      evaluated. Most importantly, this automated approach can be widely applied for
      discovery of potential drugs as well as molecular pathway elucidation not only in
      T. cruzi but also in other human intracellular pathogens.

PMID- 20688191
TI  - An analytical approach to characterize morbidity profile dissimilarity between
      distinct cohorts using electronic medical records.
AB  - We describe a two-stage analytical approach for characterizing morbidity profile
      dissimilarity among patient cohorts using electronic medical records. We capture
      morbidities using the International Statistical Classification of Diseases and
      Related Health Problems (ICD-9) codes. In the first stage of the approach
      separate logistic regression analyses for ICD-9 sections (e.g., "hypertensive
      disease" or "appendicitis") are conducted, and the odds ratios that describe
      adjusted differences in prevalence between two cohorts are displayed graphically.
      In the second stage, the results from ICD-9 section analyses are combined into a
      general morbidity dissimilarity index (MDI). For illustration, we examine nine
      cohorts of patients representing six phenotypes (or controls) derived from five
      institutions, each a participant in the electronic MEdical REcords and GEnomics
      (eMERGE) network. The phenotypes studied include type II diabetes and type II
      diabetes controls, peripheral arterial disease and peripheral arterial disease
      controls, normal cardiac conduction as measured by electrocardiography, and
      senile cataracts.

PMID- 20688192
TI  - A comparison of machine learning techniques for detection of drug target
      articles.
AB  - Important progress in treating diseases has been possible thanks to the
      identification of drug targets. Drug targets are the molecular structures whose
      abnormal activity, associated to a disease, can be modified by drugs, improving
      the health of patients. Pharmaceutical industry needs to give priority to their
      identification and validation in order to reduce the long and costly drug
      development times. In the last two decades, our knowledge about drugs, their
      mechanisms of action and drug targets has rapidly increased. Nevertheless, most
      of this knowledge is hidden in millions of medical articles and textbooks.
      Extracting knowledge from this large amount of unstructured information is a
      laborious job, even for human experts. Drug target articles identification, a
      crucial first step toward the automatic extraction of information from texts,
      constitutes the aim of this paper. A comparison of several machine learning
      techniques has been performed in order to obtain a satisfactory classifier for
      detecting drug target articles using semantic information from biomedical
      resources such as the Unified Medical Language System. The best result has been
      achieved by a Fuzzy Lattice Reasoning classifier, which reaches 98% of ROC area
      measure.

PMID- 20688193
TI  - To the Editor--PVCs and left ventricular function.

PMID- 20688196
TI  - Bone substitutes in the Netherlands - a systematic literature review.
AB  - Autologous bone grafting is currently considered as the gold standard to restore
      bone defects. However, clinical benefit is not guaranteed and there is an
      associated 8-39% complication rate. This has resulted in the development of
      alternative (synthetic) bone substitutes. The aim of this systematic literature
      review was to provide a comprehensive overview of literature data of bone
      substitutes registered in the Netherlands for use in trauma and orthopedic
      surgery. Brand names of selected products were used as search terms in three
      available databases: Embase, PubMed and Cochrane. Manuscripts written in English,
      German or Dutch that reported on structural, biological or biomechanical
      properties of the pure product or on its use in trauma and orthopedic surgery
      were included. The primary search resulted in 475 manuscripts from PubMed, 653
      from Embase and 10 from Cochrane. Of these, 218 met the final inclusion criteria.
      Of each product, structural, biological and biomechanical characteristics as well
      as their clinical indications in trauma and orthopedic surgery are provided. All
      included products possess osteoconductive properties but differ in resorption
      time and biomechanical properties. They have been used for a wide range of
      clinical applications; however, the overall level of clinical evidence is low.
      The requirements of an optimal bone substitute are related to the size and
      location of the defect. Calcium phosphate grafts have been used for most trauma
      and orthopedic surgery procedures. Calcium sulphates were mainly used to restore
      bone defects after tumour resection surgery but offer minimal structural support.
      Bioactive glass remains a potential alternative; however, its use has only been
      studied to a limited extent.

PMID- 20688195
TI  - Avoiding deep inspirations increases the maximal response to methacholine without
      altering sensitivity in non-asthmatics.
AB  - Airway hyperresponsiveness is characterised by a leftward shift of the dose
      response curve (DRC) and an increase in the maximal response. Deep inspiration
      (DI) avoidance increases responsiveness in non-asthmatic, but not asthmatic,
      subjects. The aim was to determine the effect of DI avoidance on the sensitivity
      and maximal response of the FEV(1) DRC to methacholine. Thirteen non-asthmatic
      and ten asthmatic subjects underwent a standard cumulative high-dose methacholine
      challenge (0.1-200MUmol). Subsequently, on separate days, increasing single doses
      of methacholine were administered after 10min of DI avoidance. A sigmoidal
      equation was fitted to the data to obtain values for alpha, the position
      constant, as a measure of sensitivity. The fall in FEV(1) at the highest common
      dose was used as a measure of the maximal response. The change in flow at 40%
      control vital capacity on the maximal (V40m) and partial (V40p) curves were
      calculated from the first manoeuvre after methacholine and the ratio of the
      values for V40m and V40p was calculated as a measure of the bronchodilator effect
      of DI (BD(DI)). In non-asthmatic subjects, avoiding DI increased the maximum fall
      in FEV(1) at the highest common dose (p=0.0001) but did not alter alpha (p=0.75).
      Avoiding DI before challenge did not alter BD(DI) (p=0.13). DI avoidance had no
      effect on airway responsiveness in asthmatic subjects. In non-asthmatic subjects,
      DI avoidance increases airway responsiveness by increasing the maximal response,
      but does not alter the sensitivity, suggesting that the loss of the effect of DI
      in asthma contributes to excessive bronchoconstriction.

PMID- 20688197
TI  - Synthesis, characterization and in vitro cell compatibility study of a poly(amic
      acid) graft/cross-linked poly(vinyl alcohol) hydrogel.
AB  - Although physically cross-linked poly(vinyl alcohol) (PVA) hydrogels have tunable
      mechanical properties to match that of soft tissues, such as vascular tissue,
      their hydrophilic nature is not conducive to cell adhesion and spreading. For
      applications such as small diameter vascular grafts for coronary bypass both
      mechanical matching and hemocompatibility are important. Poly(amic acid) (PAA),
      derived from ethylene diamine tetraacetic dianhydride, is a cell-compatible
      polymer. It was grafted/cross-linked onto physically cross-linked PVA to provide
      cell compatibility. Functionalization was achieved via a one-step esterification
      reaction using 1,3-dicyclohexylcarbodiimide as the coupling agent and 4
      dimethylaminopyridine as the catalyst. The success of the grafting reaction was
      verified using Fourier transform infrared spectroscopy, solid-state nuclear
      magnetic resonance spectroscopy and X-ray photoelectron spectroscopy. The
      mechanical properties of the starting PVA hydrogel were largely preserved after
      the grafting reaction within the physiological strain range of vascular tissue.
      In vitro cell culture studies using primary porcine endothelial cells confirmed
      cell compatibility of the PAA graft PVA hydrogel, making it an attractive
      candidate for small diameter vascular graft development.

PMID- 20688198
TI  - The effect of immobilized RGD peptide in alginate scaffolds on cardiac tissue
      engineering.
AB  - Cardiac tissue engineering aims to regenerate damaged myocardial tissues by
      applying heart patches created in vitro. The present study was undertaken to
      explore the possible role of matrix-attached RGD peptide in the engineering of
      cardiac tissue within macroporous scaffolds. Neonatal rat cardiac cells were
      seeded into RGD-immobilized or unmodified alginate scaffolds. The immobilized RGD
      peptide promoted cell adherence to the matrix, prevented cell apoptosis and
      accelerated cardiac tissue regeneration. Within 6 days, the cardiomyocytes
      reorganized their myofibrils and reconstructed myofibers composed of multiple
      cardiomyocytes in a typical myofiber bundle. The nonmyocyte cell population,
      mainly cardiofibroblasts, benefited greatly from adhering to the RGD-alginate
      matrix and consequently supported the cardiomyocytes. They often surrounded
      bundles of cardiac myofibers in a manner similar to that of native cardiac
      tissue. The benefits of culturing the cardiac cells in RGD-immobilized alginate
      scaffolds were further substantiated by Western blotting, revealing that the
      relative expression levels of alpha-actinin, N-cadherin and connexin-43 were
      better maintained in cells cultured within these scaffolds. Collectively, the
      immobilization of RGD peptide into macroporous alginate scaffolds proved to be a
      key parameter in cardiac tissue engineering, contributing to the formation of
      functional cardiac muscle tissue and to a better preservation of the regenerated
      tissue in culture.

PMID- 20688199
TI  - Culture media for the differentiation of mesenchymal stromal cells.
AB  - Mesenchymal stromal cells (MSCs) can be isolated from various tissues such as
      bone marrow aspirates, fat or umbilical cord blood. These cells have the ability
      to proliferate in vitro and differentiate into a series of mesoderm-type
      lineages, including osteoblasts, chondrocytes, adipocytes, myocytes and vascular
      cells. Due to this ability, MSCs provide an appealing source of progenitor cells
      which may be used in the field of tissue regeneration for both research and
      clinical purposes. The key factors for successful MSC proliferation and
      differentiation in vitro are the culture conditions. Hence, we here summarize the
      culture media and their compositions currently available for the differentiation
      of MSCs towards osteogenic, chondrogenic, adipogenic, endothelial and vascular
      smooth muscle phenotypes. However, optimal combination of growth factors,
      cytokines and serum supplements and their concentration within the media is
      essential for the in vitro culture and differentiation of MSCs and thereby for
      their application in advanced tissue engineering.

PMID- 20688200
TI  - Immobilization of a phosphonated analog of matrix phosphoproteins within cross
      linked collagen as a templating mechanism for biomimetic mineralization.
AB  - Immobilization of phosphoproteins on a collagen matrix is important for the
      induction of intrafibrillar apatite mineralization. Unlike phosphate esters,
      polyphosphonic acid has no reactive sites for covalent binding to collagen amine
      groups. Binding of poly(vinyl phosphonic acid) (PVPA), a biomimetic templating
      analog of matrix phosphoproteins, to collagen was found to be electrostatic in
      nature. Thus, an alternative retention mechanism was designed for immobilization
      of PVPA on collagen by cross-linking the latter with carbodiimide (EDC). This
      mechanism is based on the principle of size exclusion entrapment of PVPA
      molecules within the internal water compartments of collagen. By cross-linking
      collagen with EDC, a zero length cross-linking agent, the sieving property of
      collagen is increased, enabling the PVPA to be immobilized within the collagen.
      The absence of covalent cross-linking between PVPA and collagen was confirmed by
      Fourier transform infrared spectroscopy. Based on these results, a concentration
      range for immobilized PVPA to template intrafibrillar apatite deposition was
      established and validated using a single layer reconstituted type I collagen
      mineralization model. In the presence of a polyacrylic acid-containing
      mineralization medium optimal intrafibrillar mineralization of the EDC-cross
      linked collagen was achieved using 500 and 1000 MUg ml-1 PVPA. The mineralized
      fibrils exhibited a hierarchical order of intrafibrillar mineral infiltration, as
      manifested by the appearance of electron-dense periodicity within unstained
      fibrils. Understanding the basic processes in intrafibrillar mineralization of
      reconstituted collagen creates opportunities for the design of tissue engineering
      materials for hard tissue repair and regeneration.

PMID- 20688201
TI  - Perspectives - August 2010.

PMID- 20688202
TI  - An emerging phenotype of proximal 11q deletions.
AB  - Few reports of small interstitial chromosome 11q deletions are reported in the
      literature and no clear genotype-phenotype correlation has been demonstrated. We
      describe a five years old boy who was referred to our attention because of the
      presence of ptosis of the left eyelid, iris coloboma and developmental delay.
      Clinical examination also revealed the presence of dysmorphic features including:
      low frontal hairline, flat profile, round face, full cheeks, periorbital
      fullness, hypertelorism, broad nasal bridge, down-turned corners of the mouth.
      Cytogenetic analysis, performed by array-CGH (resolution 1 Mb), revealed a
      deletion of chromosome 11q13.5q14.2. The present case represents a further
      patient described in the literature with a small interstitial deletion of
      chromosome 11q. Our patient shares the dysmorphic features and the presence of
      developmental delay with the previously reported patients with overlapping
      proximal 11q deletion. Considering these clinical and cytogenetic similarities,
      we suggest the existence of an emerging syndrome associated to proximal 11q
      deletions.

PMID- 20688203
TI  - Optical advances in skeletal imaging applied to bone metastases.
AB  - Optical Imaging has evolved into one of the standard molecular imaging modalities
      used in pre-clinical cancer research. Bone research however, strongly depends on
      other imaging modalities such as SPECT, PET, x-ray and MUCT. Each imaging
      modality has its own specific strengths and weaknesses concerning spatial
      resolution, sensitivity and the possibility to quantify the signal. An increasing
      number of bone specific optical imaging models and probes have been developed
      over the past years. This review gives an overview of optical imaging modalities,
      models and probes that can be used to study skeletal complications of cancer in
      small laboratory animals.

PMID- 20688204
TI  - Long-term studies of the natural history of asthma in childhood.
AB  - Segmentation of children with asthma and other wheezy disorders remains the main
      research challenge today, as it was when described 2 centuries ago. Early
      childhood wheezy disorders follow different temporal trajectories, probably
      representing different underlying mechanisms (endophenotypes). Prospective
      identification of endophenotypes allowing accurate prediction of the clinical
      course is currently not possible. The variability of the clinical course remains
      an enigma and difficult to predict. Three of 4 school-aged children with asthma
      have outgrown disease by midadulthood. The risk of persistence increases with
      severity, sensitization, smoking, and female sex. Genetic risk variants might
      help disentangle the heterogeneity of asthma and other wheezy disorders. At early
      school age, children with asthma have reduced lung function. It is an important
      and unresolved question whether the airflow limitation associated with asthma
      already existed at birth or developed along with symptoms. Likewise, the
      association between the infant's bronchial responsiveness and development of
      asthma and other wheezy disorders is unclear. Neither primary prevention through
      manipulation of environmental factors nor secondary prevention through the use of
      inhaled corticosteroids can effectively halt the long-term disease progression in
      childhood. In conclusion, the natural history of asthma and the associated airway
      changes is still poorly understood, and we have not managed to translate findings
      from long-term studies into a deeper understanding of the underlying
      endophenotypes or improved disease management. We propose the need for a
      translational research approach based on long-term clinical studies of birth
      cohorts with comprehensive and objective assessments of intermediate phenotypes
      and environmental exposures combined with interdisciplinary basic research and a
      systems biology approach.

PMID- 20688205
TI  - Using genetics to predict the natural history of asthma?
AB  - Clinical practice reminds us that there is considerable variability in the course
      of asthma over time. Treatment of patients with asthma would be considerably
      improved if one could accurately predict the likely course of disease over the
      life course. Recently, with the advent of the era of genome-wide association
      studies, there has been a monumental shift in our understanding of the genetic
      factors that underlie inherited susceptibility to asthma. Genes have been
      identified that modulate many aspects of the natural history of asthma, such as
      susceptibility to atopy, altered lung development, and susceptibility to more
      severe disease. Heritability studies have even suggested a role for genetic
      factors in remission of asthma. However, although the discovery of novel genetic
      factors underlying disease susceptibility has undoubtedly improved our
      understanding of disease pathogenesis, whether these advances have improved the
      ability to predict the natural history in individual patients is questionable,
      and the application of genetic testing to clinical practice remains some way off.

PMID- 20688207
TI  - An hourglass-type supravalvular aortic stenosis.

PMID- 20688208
TI  - Cirrhotic cardiomyopathy.
AB  - Cirrhotic cardiomyopathy is a clinical syndrome in patients with liver cirrhosis
      characterized by an abnormal and blunted response to physiologic, pathologic, or
      pharmacologic stress but normal to increased cardiac output and contractility at
      rest. As many as 50% of cirrhotic patients undergoing liver transplantation show
      signs of cardiac dysfunction, and 7% to 21% of deaths after orthotopic liver
      transplantation result from overt heart failure. In this review, we critically
      evaluate the existing literature on the pathophysiology and clinical implications
      of cirrhotic cardiomyopathy.

PMID- 20688209
TI  - Effectiveness of in-laboratory high-dose clopidogrel loading versus routine pre
      load in patients undergoing percutaneous coronary intervention: results of the
      ARMYDA-5 PRELOAD (Antiplatelet therapy for Reduction of MYocardial Damage during
      Angioplasty) randomized trial.
AB  - OBJECTIVES: This study sought to evaluate safety and effectiveness of in
      laboratory (in-lab) 600-mg clopidogrel loading pre-percutaneous coronary
      intervention (PCI) versus routine 6-h pre-load. BACKGROUND: Clopidogrel pre
      treatment significantly improves outcome in patients undergoing PCI; however,
      efficacy of an in-lab loading strategy before PCI after coronary angiography
      versus routine pre-load has not been fully characterized. METHODS: A total of 409
      patients (39% with acute coronary syndrome) were randomized to receive a 600-mg
      clopidogrel loading dose 4 to 8 h before PCI (pre-load group, n = 204) or a 600
      mg loading dose given in the catheterization lab after coronary angiography, but
      prior to PCI (in-lab group, n = 205). Primary end point was 30-day incidence of
      major adverse cardiac events: cardiac death, myocardial infarction (MI), or
      unplanned target vessel revascularization. RESULTS: There was no significant
      difference in primary end point between the 2 randomization arms (8.8% in-lab vs.
      10.3% pre-load; p = 0.72); this was mainly driven by periprocedural MI (8.8% vs.
      9.3%, p = 0.99). No increased risk of bleeding or vascular complications was
      observed in the pre-load arm (5.4% vs. 7.8%; p = 0.42). As determined by the
      VerifyNow assay (Accumetrics, San Diego, California), patients in the in-lab
      group showed higher platelet reactivity during PCI and 2 h after intervention
      versus those in the pre-load arm (p < or = 0.043). CONCLUSIONS: ARMYDA-5 PRELOAD
      (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty)
      trial indicates that a strategy of 600-mg in-lab clopidogrel load pre-PCI may
      have similar clinical outcomes as routine 4- to 8-h pre-load. Thus, when
      indicated, in-lab clopidogrel administration can be a safe alternative to routine
      pre-treatment given before knowing patients' coronary anatomy.

PMID- 20688210
TI  - In-laboratory high-dose clopidogrel loading: do we need a mirror of diamond for
      "Armida's garden"?

PMID- 20688211
TI  - Assessment of advanced coronary artery disease: advantages of quantitative
      cardiac magnetic resonance perfusion analysis.
AB  - OBJECTIVES: The purpose of this paper was to compare quantitative cardiac
      magnetic resonance (CMR) first-pass contrast-enhanced perfusion imaging to
      qualitative interpretation for determining the presence and severity of coronary
      artery disease (CAD). BACKGROUND: Adenosine CMR can detect CAD by measuring
      perfusion reserve (PR) or by qualitative interpretation (QI). METHODS: Forty-one
      patients with an abnormal nuclear stress scheduled for X-ray angiography
      underwent dual-bolus adenosine CMR. Segmental myocardial perfusion analyzed using
      both QI and PR by Fermi function deconvolution was compared to quantitative
      coronary angiography. RESULTS: In the 30 patients with complete quantitative
      data, PR (mean +/- SD) decreased stepwise as coronary artery stenosis (CAS)
      severity increased: 2.42 +/- 0.94 for <50%, 2.14 +/- 0.87 for 50% to 70%, and
      1.85 +/- 0.77 for >70% (p < 0.001). The PR and QI had similar diagnostic
      accuracies for detection of CAS >50% (83% vs. 80%), and CAS >70% (77% vs. 67%).
      Agreement between observers was higher for quantitative analysis than for
      qualitative analysis. Using PR, patients with triple-vessel CAD had a higher
      burden of detectable ischemia than patients with single-vessel CAD (60% vs. 25%;
      p = 0.02), whereas no difference was detected by QI (31% vs. 21%; p = 0.26). In
      segments with myocardial scar (n = 64), PR was 3.10 +/- 1.34 for patients with
      CAS <50% (n = 18) and 1.91 +/- 0.96 for CAS >50% (p < 0.0001). CONCLUSIONS:
      Quantitative PR by CMR differentiates moderate from severe stenoses in patients
      with known or suspected CAD. The PR analysis differentiates triple- from single
      vessel CAD, whereas QI does not, and determines the severity of CAS subtending
      myocardial scar. This has important implications for assessment of prognosis and
      therapeutic decision making.

PMID- 20688212
TI  - Impact of left atrial volume on clinical outcome in organic mitral regurgitation.
AB  - OBJECTIVES: The purpose of this paper was to assess the link between left atrial
      (LA) volume at diagnosis and outcome of patients with mitral regurgitation (MR).
      BACKGROUND: Left atrial enlargement is a consequence of organic MR, but its
      association with clinical outcome independently of MR severity is uncertain.
      METHODS: We prospectively enrolled 492 patients (age 63 +/- 15 years, 60% men) in
      sinus rhythm with organic MR (regurgitant volume 68 +/- 42 ml/beat) and performed
      at baseline triple echocardiographic quantitation (MR severity, LA volume, and
      left ventricular characteristics). Outcome with medical and surgical management
      was analyzed. RESULTS: Left atrial volume indexed to body surface area (LA index)
      was 55 +/- 26 ml/m(2) (<40 ml/m(2) in 158 patients, 40 to 59 ml/m(2) in 160
      patients, and > or =60 ml/m(2) in 174 patients). Under medical management, 5-year
      survival was 80 +/- 2.9% and cardiac events 28 +/- 3%. Adjusting for established
      predictors of outcome, LA index was independently associated with survival after
      diagnosis (hazard ratio [HR]: 1.3 [95% confidence interval (CI): 1.1 to 1.5] per
      10 ml/m(2) increment, p = 0.001). Patients with LA index > or =60 ml/m(2) had
      lower 5-year survival than those with no or mild LA enlargement (p < 0.0001) and
      than the rates of survival expected in the U.S. population (53 +/- 8.6% vs. 76%,
      p = 0.017). Compared with patients with LA index <40 ml/m(2), those with LA index
      > or =60 ml/m(2) had increased mortality (HR: 2.8 [95% CI: 1.2 to 6.5], p =
      0.016) and cardiac events (HR: 5.2 [95% CI: 2.6 to 10.9], p < 0.0001) with
      medical management. Mitral surgery was associated with decreased mortality (HR:
      0.46 [95% CI: 0.26 to 0.84], p = 0.01) and cardiac events (HR: 0.38 [95% CI: 0.23
      to 0.62], p = 0.0001) and after surgery patients with LA index > or =60 ml/m(2)
      versus <60 ml/m(2) did not incur excess mortality or cardiac events (both p >
      0.30). CONCLUSIONS: In organic MR, LA index at diagnosis predicts long-term
      outcome, incrementally to known predictors of outcome. This marker of risk is
      particularly important because mitral surgery in these patients markedly improves
      outcome and restores life expectancy. LA index should be measured in routine
      clinical practice for risk-stratification and for clinical decision making in
      patients with organic MR.

PMID- 20688213
TI  - Looking into the left atrial crystal ball: a ray of hope for patients with
      organic mitral regurgitation.

PMID- 20688214
TI  - Viral endomyocardial infection is an independent predictor and potentially
      treatable risk factor for graft loss and coronary vasculopathy in pediatric
      cardiac transplant recipients.
AB  - OBJECTIVES: This study sought to evaluate the outcome and prevalence of viral
      endomyocardial infection after cardiac transplantation. BACKGROUND: Viral
      myocardial infection causes heart failure, but its role after cardiac
      transplantation is unclear. We hypothesized that viral infection of the cardiac
      allograft reduces graft survival. METHODS: Between June 1999 and November 2004,
      94 pediatric cardiac transplant patients were screened for the presence of viral
      genome in serial endomyocardial biopsies (EMBs) using polymerase chain reaction
      (PCR) assays. Graft loss, advanced transplant coronary artery disease (TCAD), and
      acute rejection (AR) were compared in the PCR-positive (n = 37) and PCR-negative
      (n = 57) groups, using time-dependent Kaplan-Meier and Cox regression analyses.
      From November 2002 to November 2004, intravenous immunoglobulin therapy (IVIG)
      was administered to patients with PCR-positive EMBs. The outcomes of the IVIG
      treated, PCR-positive patients (n = 20) were compared with IVIG-untreated, PCR
      positive patients (n = 17). RESULTS: Viral genomes were detected in EMBs from 37
      (39%) patients; parvovirus B19, adenovirus, and Epstein-Barr virus (EBV) were the
      most common. The PCR-positive group (n = 37, 25% graft loss at 2.4 years) had
      decreased graft survival (p < 0.001) compared with the PCR-negative group (n =
      57, 25% graft loss at 8.7 years) and developed advanced TCAD prematurely (p =
      0.001). The number of AR episodes was similar in both groups. On multivariate
      analysis, presence of viral genome was an independent risk factor for graft loss
      (relative risk: 4.2, p = 0.015). The time to advanced TCAD after becoming PCR
      positive was longer in the IVIG-treated patients (p = 0.03) with a trend toward
      improved graft survival (p = 0.06). CONCLUSIONS: Viral endomyocardial infection
      is an independent predictor of graft loss in pediatric cardiac transplant
      recipients. This effect appears to be mediated through premature development of
      advanced TCAD. IVIG therapy in this subgroup may improve survival and merits
      further investigation.

PMID- 20688215
TI  - Human peripheral blood-derived CD31+ cells have robust angiogenic and
      vasculogenic properties and are effective for treating ischemic vascular disease.
AB  - OBJECTIVES: This study aimed to determine if CD31 is a novel marker of a
      circulating angio-vasculogenic cell population and to establish the cells'
      therapeutic effects on experimental ischemia. BACKGROUND: Emerging evidence
      suggested that therapeutic mechanisms underlying various bone marrow-derived
      cells are due to paracrine effects. Furthermore, the vasculogenic potential of
      these cells is under debate. CD31 is a well-known marker for endothelial cells
      but is also expressed in a fraction of peripheral blood (PB) mononuclear cells.
      METHODS: CD31(+) cells were isolated from human PB by magnetic-activated cell
      sorting. The gene expression profile was examined by deoxyribonucleic acid
      microarray and real-time reverse transcriptase polymerase chain reaction. Various
      in vitro endothelial differentiation or vasculogenic assays were conducted.
      Finally, cells were directly implanted into a mouse hind limb ischemia model to
      test angiogenic-vasculogenic and therapeutic effects. RESULTS: Fluorescent
      activated cell sorter analysis revealed that PB-CD31(+) cells exhibited
      endothelial and hematopoietic stem/progenitor markers. CD31(+) cells had higher
      levels of expression of proangiogenic genes on microarray and real-time reverse
      transcriptase polymerase chain reaction and generated higher numbers of
      endothelial progenitor cells than CD31(-) cells did. CD31(+) cells spontaneously
      formed vascular tubelike structures and exhibited an endothelial cell phenotype
      in vitro. In a hind limb ischemia model, CD31(+) cell transplantation augmented
      blood perfusion and prevented limb loss. Both angiogenic cytokines and capillary
      density were increased, suggesting CD31(+) cells augmented neovascularization.
      CONCLUSIONS: CD31 is a novel marker that designates circulating angiogenic and
      vasculogenic cells. These cells are easily isolated from human PB and thus are a
      novel candidate for treatment of ischemic cardiovascular disease.

PMID- 20688216
TI  - Peripheral blood CD31+ cells for the treatment of ischemic vascular disease.

PMID- 20688217
TI  - An unusual cause of anterior mediastinal mass.

PMID- 20688218
TI  - Zero coronary calcium and Bayes' theorem.

PMID- 20688219
TI  - What is the real negative predictive value of a zero calcium score?

PMID- 20688220
TI  - What is the prognostic value of a zero calcium score? Ask Bayes!

PMID- 20688221
TI  - Coronary calcification and coronary artery disease.

PMID- 20688222
TI  - Coronary calcium remains an effective filter for invasive angiography.

PMID- 20688225
TI  - Evaluation of pulsed electric fields technology for liquid whole egg
      pasteurization.
AB  - This investigation evaluated the lethal efficiency of pulsed electric fields
      (PEFs) to pasteurize liquid whole egg (LWE). To achieve this aim, we describe the
      inactivation of Salmonella Enteritidis and the heat resistant Salmonella
      Senftenberg 775 W in terms of treatment time and specific energy at electric
      field strengths ranging from 20 to 45 kV/cm. Based on our results, the target
      microorganism for this technology in LWE varied with intensity of the PEF
      treatment. For electric field strengths greater than 25 kV/cm, Salmonella
      Enteritidis was the most PEF-resistant strain. For this Salmonella serovar the
      level of inactivation depended only on the specific energy applied: i.e., 106,
      272, and 472 kJ/kg for 1, 2, and 3 Log(10) reductions, respectively. The
      developed mathematical equations based on the Weibull distribution permit
      estimations of maximum inactivation level of 1.9 Log(10) cycles of the target
      Salmonella serovar in the best-case scenario: 250 kJ/kg and 25 kV/cm. This level
      of inactivation indicates that PEF technology by itself cannot guarantee the
      security of LWE based on USDA and European regulations. The occurrence of cell
      damage due to PEF in the Salmonella population opens the possibility of designing
      combined processes enabling increased microbial lethality in LWE.

PMID- 20688226
TI  - Profile of volatile compounds during papaya juice fermentation by a mixed culture
      of Saccharomyces cerevisiae and Williopsis saturnus.
AB  - This study investigated the formation and utilization of volatile compounds
      during papaya juice fermentation by a mixed culture of Saccharomyces cerevisiae
      and Williopsis saturnus. Time-course papaya juice fermentations were carried out
      using pure cultures of S. cerevisiae var. bayanus R2 and W. saturnus var. mrakii
      NCYC2251 and a mixed culture of the two yeasts at a ratio of 1:1000
      (R2:NCYC2251). Changes in S. cerevisiae cell population, Brix, sugar consumption
      and pH were similar in the mixed culture and in the S. cerevisiae monoculture.
      There was an early growth arrest of W. saturnus in the mixed culture
      fermentation. A range of volatile compounds were produced during fermentation
      including fatty acids, alcohols, aldehydes and esters and some volatile compounds
      including those initially present in the juice were utilized. The mixed culture
      fermentation of S. cerevisiae and W. saturnus benefited from the presence of both
      yeasts, with more esters being produced than the S. cerevisiae monoculture and
      more alcohols being formed than the W. saturnus monoculture. The study suggests
      that papaya juice fermentation with a mixed culture of S. cerevisiae and W.
      saturnus may be able to result in the formation of more complex aroma compounds
      and higher ethanol level than those using single yeasts.

PMID- 20688227
TI  - Fate of Escherichia coli O157:H7, Salmonella and Listeria innocua on minimally
      processed peaches under different storage conditions.
AB  - Consumption of fresh-cut produce has sharply increased recently causing an
      increase of foodborne illnesses associated with these products. As generally,
      acidic fruits are considered 'safe' from a microbiological point of view, the aim
      of this work was to study the growth and survival of Escherichia coli O157:H7,
      Salmonella and Listeria innocua on minimally-processed peaches. The three
      foodborne pathogens population increased more than 2 log(10)units on fresh-cut
      peach when stored at 20 and 25 degrees C after 48 h. At 10 degrees C only L.
      innocua grew more than 1 log(10)unit and it was the only pathogen able to grow at
      5 degrees C. Differences in growth occurred between different peach varieties
      tested, with higher population increases in those varieties with higher pH
      ('Royal Glory' 4.73+/-0.25 and 'Diana' 4.12+/-0.18). The use of common strategies
      on extending shelf life of fresh-cut produce, as modified atmosphere packaging
      and the use of the antioxidant substance, ascorbic acid (2%w/v), did not affect
      pathogens' growth at any of the temperatures tested (5 and 25 degrees C).
      Minimally-processed peaches have shown to be a good substrate for foodborne
      pathogens' growth regardless use of modified atmosphere and ascorbic acid.
      Therefore, maintaining cold chain and avoiding contamination is highly necessary.

PMID- 20688228
TI  - Characterisation of an antiviral pediocin-like bacteriocin produced by
      Enterococcus faecium.
AB  - The bacteriocin-producing strain Enterococcus faecium ST5Ha was isolated from
      smoked salmon and identified by biomolecular techniques. Ent. faecium ST5Ha
      produces a pediocin-like bacteriocin with activity against several lactic acid
      bacteria, Listeria spp. and some other human and food pathogens, and remarkably
      against HSV-1 virus. Bacteriocin ST5Ha was produced at high levels in MRS broth
      at 30 degrees C and 37 degrees C, reaching a maximum production of 1.0 x 10(9)
      AU/ml, checked against Listeria ivanovii ATCC19119 as target strain and surrogate
      of pathogenic strain Listeria monocytogenes. The molecular weight of bacteriocin
      ST5Ha was estimated to be 4.5 kDa according to tricine-SDS-PAGE data. Ent.
      faecium ST5Ha harbors a 1.044 kb chromosomal DNA fragment fitting in size to that
      of pediocin PA-1/AcH. In addition, the sequencing of bacteriocin ST5Ha gene
      indicated 99% of DNA homology to pediocin PA-1/AcH. The combined application of
      low levels (below MIC) of ciprofloxacin and bacteriocin ST5Ha resulted in a
      synergetic effect in the inhibition of target strain L. ivanovii ATCC19119.
      Bacteriocin ST5Ha displayed antiviral activity against HSV-1, an important human
      pathogen, with a selectivity index of 173. To the best of our knowledge, this is
      the first report on Ent. faecium as a potential producer of pediocin-like
      bacteriocin with antiviral activity.

PMID- 20688229
TI  - The effect of ripening and storage conditions on the distribution of tyramine,
      putrescine and cadaverine in Edam-cheese.
AB  - The aim of the work was to describe the development of selected biogenic amines
      (histamine, tyramine, putrescine and cadaverine) in 4 layers of Dutch-type cheese
      (Edam-cheese) depending on 3 ripening/storage regimes during a 98-day period.
      Biogenic amines were analysed by means of ion-exchange chromatography. A further
      goal was to identify microbial sources of biogenic amines in the material
      analysed. Phenotype characterization and repetitive sequence-based PCR
      fingerprinting were used to identify the isolated bacteria. The highest content
      of tyramine, putrescine and cadaverine was determined in cheeses stored in a
      ripening cellar at a temperature of 10 degrees C during the whole observation
      period. Lower biogenic amines content was determined in samples which were moved
      into a cold storage device (5 degrees C) after 38 days of storage in a ripening
      cellar (10 degrees C). The lowest concentrations of biogenic amines were detected
      in cheeses which were moved into a cold storage device (5 degrees C) after 23
      days of storage in a ripening cellar (10 degrees C). During the 98-day period,
      histamine was not detected in any of the regimes. Within the cheeses analysed,
      non-starter lactic acid bacteria Lactobacillus curvatus, Lactobacillus
      casei/paracasei and Lactobacillus plantarum were detected as the main producers
      of the biogenic amines tested. In starter bacteria Lactococcus lactis subsp.
      lactis and Lactococcus lactis subsp. cremoris the decarboxylase activity tested
      was not detected.

PMID- 20688230
TI  - Biodegradable gelatin-chitosan films incorporated with essential oils as
      antimicrobial agents for fish preservation.
AB  - Essential oils of clove (Syzygium aromaticum L.), fennel (Foeniculum vulgare
      Miller), cypress (Cupressus sempervirens L.), lavender (Lavandula angustifolia),
      thyme (Thymus vulgaris L.), herb-of-the-cross (Verbena officinalis L.), pine
      (Pinus sylvestris) and rosemary (Rosmarinus officinalis) were tested for their
      antimicrobial activity on 18 genera of bacteria, which included some important
      food pathogen and spoilage bacteria. Clove essential oil showed the highest
      inhibitory effect, followed by rosemary and lavender. In an attempt to evaluate
      the usefulness of these essential oils as food preservatives, they were also
      tested on an extract made of fish, where clove and thyme essential oils were the
      most effective. Then, gelatin-chitosan-based edible films incorporated with clove
      essential oil were elaborated and their antimicrobial activity tested against six
      selected microorganisms: Pseudomonas fluorescens, Shewanella putrefaciens,
      Photobacterium phosphoreum, Listeria innocua, Escherichia coli and Lactobacillus
      acidophilus. The clove-containing films inhibited all these microorganisms
      irrespectively of the film matrix or type of microorganism. In a further
      experiment, when the complex gelatin-chitosan film incorporating clove essential
      oil was applied to fish during chilled storage, the growth of microorganisms was
      drastically reduced in gram-negative bacteria, especially enterobacteria, while
      lactic acid bacteria remained practically constant for much of the storage
      period. The effect on the microorganisms during this period was in accordance
      with biochemical indexes of quality, indicating the viability of these films for
      fish preservation.

PMID- 20688231
TI  - Robustness of Lactobacillus plantarum starters during daily propagation of wheat
      flour sourdough type I.
AB  - This study aimed at investigating the robustness of selected sourdough strains of
      Lactobacillus plantarum. Seven strains were singly used as sourdough type I
      starters under daily back-slopping propagation (ten days) using wheat flour. Cell
      numbers of presumptive lactic acid bacteria varied slightly (median values of
      9.13-9.46 log cfu g(-1)) between and within started sourdoughs, as well as the
      acidifying activity (median values of 1.24-1.33). After three days also the
      control sourdough (unstarted) had the same values. As shown by RAPD-PCR analysis,
      five (DB200, 3DM, G10C3, 12H1 and LP20) out of seven strains maintained elevated
      cell numbers (ca. 9 log cfu g(-1)) throughout ten days. The other two strains
      progressively decreased to less than 5 log cfu g(-1). As identified by partial
      sequencing of 16S rRNA and recA genes, L. plantarum (11 isolates), pediococci
      (7), Lactobacillus casei (3) and Lactobacillus rossiae (2) dominated the flour
      microbiota. Monitoring of lactic acid bacteria during sourdough propagation was
      carried out by culture dependent approach and using PCR-DGGE (Denaturing Gradient
      Gel Electrophoresis). Except for the sourdough started with L. plantarum LP20, in
      all other sourdoughs at least one autochthonous strain of L. plantarum emerged.
      All emerging strains of L. plantarum showed different RAPD-PCR profiles. L.
      rossiae and Pediococcus pentosaceus were only found in the control and sourdough
      started with strain 12H1. The characterization of the catabolic profiles of
      sourdoughs (Biolog System) showed that sourdoughs containing persistent starters
      behaved similarly and their profiles were clearly differentiated from the others.
      One persistent strain (DB200) of L. plantarum and Lactobacillus sanfranciscensis
      LS44, previously shown to be persistent (Siragusa et al., 2009), were used as the
      mixed starter to produce a wheat flour sourdough. Both strains cohabited and
      dominated during ten days of propagation.

PMID- 20688232
TI  - Modelling mould growth under suboptimal environmental conditions and inoculum
      size.
AB  - Predictive models can be a tool to develop strategies to prevent mould
      development and consequently mycotoxin production. The aims of this work were to
      assess the impact of a) high/low levels of inoculum and b) optimal/suboptimal
      environmental conditions on fungal responses based on both kinetic and
      probabilistic models. Different levels of spore suspensions of Aspergillus
      carbonarius and Penicillium expansum were prepared and inoculated centrally with
      a needlepoint load on malt extract agar (MEA) with 50 replicates. While optimum
      conditions led to a colony diameter increase which followed Baranyi's function,
      suboptimal conditions led to different grow functions. In general, growth rate
      (mu) and lag phase (lambda) were normally distributed. Specifically, the growth
      rate (mu) showed similar distributions under optimal growth conditions,
      regardless of the inoculum level, while suboptimal a(w) and temperature
      conditions led to higher kurtosis distributions, mainly when the inoculum levels
      were low. Regarding lambda, more skewed distributions were observed, mainly when
      the inoculum levels were low. Probability models were not much affected by the
      inoculum size. Lower probabilities of growth were in general predicted under
      marginal conditions at a given time for both strains. The slopes of the
      probability curves were smaller under suboptimal growth conditions due to wider
      distributions. Results showed that a low inoculum level and suboptimal conditions
      lead to high variability of the estimated growth parameters and growth
      probability.

PMID- 20688233
TI  - Fermentation with Bacillus spp. as a bioprocess to enhance anthocyanin content,
      the angiotensin converting enzyme inhibitory effect, and the reducing activity of
      black soybeans.
AB  - Food possessing anthocyanins, angiotensin converting enzyme (ACE) inhibitory
      activity or reducing activity show beneficial effect on human health. To develop
      healthy food, black soybeans were fermented with either Bacillus subtilis BCRC
      14715 or Bacillus sp. CN11, or a mixture of both Bacillus spp. in the present
      study. The anthocyanin content, the ACE inhibitory activity and the reducing
      power of the fermented black soybean were then examined. It was found that the
      ACE inhibitory activity of the extracts of bean and viscous material from the
      fermented black soybeans varied with extraction solvents and starter organism,
      yet increased as the fermentation period was extended, regardless of starter
      organism. After 18 h of fermentation, the water extract of bean showed less ACE
      inhibitory activity than did the respective 80% ethanol extract. While the water
      extract of viscous material showed a higher ACE inhibitory activity than the
      respective ethanol extract. With respect to extraction yield, it was found that
      the ACE inhibitor in the fermented black soybean could be extracted more
      efficiently with water than 80% ethanol. Fermentation with B. subtilis BCRC 14715
      was also found to increase the anthocyanin content of black soybean and the
      reducing activity of the extracts. Finally, the 80% ethanol extract showed a
      higher reducing activity than the water extract.

PMID- 20688234
TI  - Contribution of hydrogen peroxide to the inhibition of Staphylococcus aureus by
      Lactococcus garvieae in interaction with raw milk microbial community.
AB  - The response of Staphylococcus aureus growth inhibition by Lactococcus garvieae
      to catalase and milk lactoperoxidase, and its efficiency in raw milk cheese were
      evaluated. S. aureus and L. garvieae were co-cultivated in broth buffered at pH
      6.8, and in raw, pasteurized and microfiltered milk, in presence and absence of
      catalase. Although H2O2 production by L. garvieae was detected only in agitated
      broth, the inhibition of S. aureus by L. garvieae was reduced by catalase both in
      static and shaking cultures by 2.7 log, pasteurized milk (approximately 0.7 log),
      microfiltered milk (approximately 0.6 log) and raw milk (approximately 0.2 log).
      The growth of S. aureus alone in microfiltered milk was delayed compared with
      that in pasteurized milk and inhibition of S. aureus by L. garvieae was stronger
      in microfiltered milk. The inhibition of coagulase-positive staphylococci (CPS)
      by L. garvieae in raw milk cheese was similar to that in raw milk (approximately
      0.8 log), but weaker than that in pasteurized and microfiltered milks. L.
      garvieae also had an early antagonistic effect on the growth of several other
      microbial groups, which lastingly affected populations levels and balance during
      cheese ripening.

PMID- 20688235
TI  - Quantitative detection and identification of tyramine-producing enterococci and
      lactobacilli in cheese by multiplex qPCR.
AB  - Tyramine is the most abundant biogenic amine in fermented dairy products, in
      which it is produced through the microbial enzymatic decarboxylation of tyrosine.
      This activity has been detected in a variety of lactic acid bacteria mainly
      belonging to the genera Enterococcus and Lactobacillus. This paper describes a
      culture-independent qPCR method, based on the specific amplification of the tdc
      gene, for the detection, quantification and identification of bacteria with the
      ability to produce tyramine. This method was found to be specific and to show a
      wide dynamic range, thus allowing the quantification of these tdc+ bacterial
      groups among the complex microbiota of cheese. tdc qPCR was used to follow the
      development of tdc+ microbiota during the manufacture of a blue-veined cheese
      (Cabrales) made from raw milk. In this type of cheese, tdc+ enterococci seem to
      be responsible for the high concentrations of tyramine detected. The method was
      also used to identify and quantify tdc+ enterococci and lactobacilli in 18
      commercially available cheeses. Different types and numbers of these
      microorganisms were found. Their relationships with the concentration of tyramine
      and technological factors are discussed.

PMID- 20688236
TI  - Potential of nisin-incorporated sodium caseinate films to control Listeria in
      artificially contaminated cheese.
AB  - A sodium caseinate film containing nisin (1000 IU/cm(2)) was produced and used to
      control Listeria innocua in an artificially contaminated cheese. Mini red Babybel
      cheese was chosen as a model semi-soft cheese. L. innocua was both surface- and
      in-depth inoculated to investigate the effectiveness of the antimicrobial film as
      a function of the distance from the surface in contact with the film. The
      presence of the active film resulted in a 1.1 log CFU/g reduction in L. innocua
      counts in surface-inoculated cheese samples after one week of storage at 4
      degrees C as compared to control samples. With regard to in-depth inoculated
      cheese samples, antimicrobial efficiency was found to be dependent on the
      distance from the surface in contact with the active films to the cheese matrix.
      The inactivation rates obtained were 1.1, 0.9 and 0.25 log CFU/g for distances
      from the contact surface of 1 mm, 2 mm and 3 mm, respectively. Our study
      demonstrates the potential application of sodium caseinate films containing nisin
      as a promising method to overcome problems associated with post-process
      contamination, thereby extending the shelf life and possibly enhancing the
      microbial safety of cheeses.

PMID- 20688237
TI  - The application of staphylococci with flavour-generating potential is affected by
      acidification in fermented dry sausages.
AB  - Differences in the production of bacterial metabolites with potential impact on
      fermented sausage flavour were found in meat simulation medium when comparing
      different strains of Staphylococcus xylosus and Staphylococcus carnosus as
      starter cultures. Overall, higher levels of 3-methyl-1-butanol and acetoin were
      found for S. xylosus, with some intraspecies variability. In addition, sausage
      fermentation parameters affected staphylococcal growth and metabolism. Strong
      acidification, as in Northern-European types of fermented dry sausage, inhibited
      S. xylosus 3PA6 but not S. carnosus 833. During a milder, Southern-European type
      of acidification, both strains displayed survival over time. During in situ
      sausage trials, variations in the degree of acidification and the choice of
      starter microorganisms were of importance, whereas modifications in fat and salt
      contents had no effects. Staphylococcus sciuri alphaSg2, Staphylococcus succinus
      4PB1, and S. xylosus 3PA6 were unable to survive the fermentation of a Northern
      European type of fermented dry sausage, characterized by low or no 3-methyl-1
      butanol and acetoin production. Inoculation with S. sciuri alphaSg2, S. succinus
      4PB1, or S. xylosus 3PA6 led to 3-methyl-1-butanol and acetoin production in
      Southern-European type of fermented dry sausages, which was not observed with S.
      carnosus 833.

PMID- 20688238
TI  - Isolation and identification of Enterococcus faecium from seafoods: antimicrobial
      resistance and production of bacteriocin-like substances.
AB  - A collection of isolates from uncooked seafoods (molluscs, fish, and fish
      fillets) were identified as Enterococcus faecium species and studied in further
      detail. Isolates were clustered in well-defined genomic groups according to food
      origin after ERIC-PCR analysis. Four isolates (FR 1-2, FB 1-3-B, FB 3-1, FTA 1-2)
      decarboxylated lysine, ornithine, and tyrosine. Isolate FR 1-2 also
      decarboxylated histidine. Most isolates were sensitive to antibiotics of clinical
      use, but resistance was detected more frequently towards nitrofurantoin (50%),
      erythromycin (33.33%) or rifampicin (33.33%) to quinupristin/dalfopristin
      (12.5%). Resistance to beta-lactams or vancomycin was not detected. The
      enterococcal antigen A was the presumed virulence trait detected most frequently.
      None of isolates carried haemolysin/cytolysin genes. Twelve isolates produced
      anti-listerial activity. Among them, seven isolates also produced bacteriocin
      like inhibitory substances against other enterococci, and one isolate was also
      able to inhibit Staphylococcus aureus. Three isolates only were active against
      Listeria monocytogenes, and two only were active against enterococci. One
      bacteriocinogenic isolate carried the enterocin A structural gene, but genes
      corresponding to other enterocins (EntB, EntP, EntQ, Ent1071, EntL50A/EntL50B,
      and Ent31) were not detected. Bacteriocin-producing enterococci lacking
      undesirable traits (such as antibiotic resistance or biogenic amine production)
      or their produced bacteriocins could be potential candidates to aid in
      preservation of seafoods and other food products as well.

PMID- 20688239
TI  - A predictive microbiology approach for thermal inactivation of Hepatitis A virus
      in acidified berries.
AB  - Hepatitis A virus (HAV) is a food-borne enteric virus responsible for outbreaks
      of hepatitis associated with consumption of raw vegetables. Soft fruits, such as
      red berries, exposed to faecal contamination are increasingly responsible for
      collective food-borne illnesses associated with HAV, when eaten raw or used in
      unprocessed foods. Heat is the most effective measure for the inactivation of
      HAV. Thermal treatments are used on fruits as a decontamination method, but they
      have to be adapted to product characteristics; indeed, factors such as sugar or
      pH may have an impact on the viral sensitivity to thermal treatments. A model was
      developed for the inactivation of HAV in red berries without supplemented sugar
      and with different pH values. Nonlinear inactivation curves in acidified
      raspberries were modelled using an integrated model, with a single equation
      nesting secondary models of temperature and pH in the primary model. Model
      predictions were then confronted to experimental results obtained in another
      laboratory on other berries with different pH values. Excellent predictions were
      obtained in most cases, while failed predictions provided safe results, with the
      model predicting higher residual virus titres than what was observed.

PMID- 20688240
TI  - Effect of fermentation by pure and mixed cultures of Streptococcus thermophilus
      and Lactobacillus helveticus on isoflavone and B-vitamin content of a fermented
      soy beverage.
AB  - Enhancement of nutritional or vitamin content of foods is commonly touted as a
      major benefit of probiotics. In this paper, we examined the ability of three
      probiotic bacteria either alone or in combination to enhance nutritional content.
      Pure and mixed cultures of Streptococcus thermophilus ST5 and Lactobacillus
      helveticus R0052 or Bifidobacterium longum R0175 were used to prepare fermented
      soy beverages. The effects of strain, acidification and mixed cultures on the
      deconjugation of soy isoflavones were examined. Acidification to pH 4.7 alone
      resulted in a 7% drop in isoflavone levels. Deconjugation levels varied between
      the different glucosides. Fermentation by L. helveticus R0052 resulted in the 50%
      reduction in total glucosides with O-malonyl glucosides being reduced 64%.
      Fermentation by S. thermophilus ST5 or B. longum R0175 had no significant effect
      on isoflavone levels. Combining a S. thermophilus strain with a L. helveticus
      culture reduced the effectiveness of the latter. Fermentation did not
      significantly modify vitamin B1 or B6 levels.

PMID- 20688241
TI  - ANCA-associated vasculitis. Preface.

PMID- 20688242
TI  - The history of ANCA-associated vasculitis.
AB  - An essential early step toward understanding vasculitis was recognition in 1948
      of the differences between the small artery disease of polyarteritis, essentially
      sparing the glomerulus and lungs, and disease of glomerular vessels and small
      veins, often involving the lungs. By 1951, Churg and Strauss drew on their
      knowledge of vasculitis literature and renal pathology to provide an
      authoritative description of the syndrome bearing their names. One year later a
      paper from Australia described a syndrome of febrile systemic illness with
      myalgias, arthralgias, microscopic hematuria, and a serum antibody reacting with
      neutrophil cytoplasm antigens. Within 30 years, nephrologists and immunologists
      in northern Europe linked antineutrophil cytoplasm antibodies to a specific
      vasculitis, Wegener's granulomatosis. Falk and Jennette later determined that
      pANCA reacted with cytoplasmic myeloperoxidase, and that cANCA did not; the
      antigen with which cANCA reacted was soon identified as a novel serine
      proteinase. New and better treatments of AAV will follow progress in
      understanding their pathogenesis.

PMID- 20688243
TI  - Epidemiology of ANCA-associated vasculitis.
AB  - The epidemiology of the antineutrophil cytoplasm antibody (ANCA)-associated
      vasculitides (AAV), comprising Wegener's granulomatosis, microscopic
      polyangiitis, and Churg-Strauss syndrome, poses considerable challenges to
      epidemiologists. These challenges include the difficulty of defining a case with
      a lack of clear distinction between the different disorders, case capture, and
      case ascertainment. The AAV are rare and therefore a large population is required
      to determine the incidence and prevalence, and this poses questions of
      feasibility. Despite these difficulties a considerable body of data on the
      epidemiology of the AAV has been built in the past 20 years with an interesting
      age, geographic, and ethnic tropism gradually being revealed. Most of the data
      come from White populations of European descent, and the overall annual incidence
      is estimated at approximately 10-20/million with a peak age of onset in those
      aged 65 to 74 years.

PMID- 20688245
TI  - Autoantibodies in ANCA-associated vasculitis.
AB  - Antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides are
      systemic or more limited conditions characterized by necrotizing destruction of
      small and medium-sized vessels (eg, capillaries, venules, and arterioles). ANCAs
      are the most predominant autoantibodies in patients affected by vasculitis, but
      other autoantibodies may also occur, probably reflecting pathogenetic events in
      affected tissue. These autoantibodies are assumed to play a role in the
      initiation and propagation of chronic inflammation. ANCAs are valuable for
      clinical diagnosis, follow-up, and guidance in therapy.

PMID- 20688246
TI  - Diagnostic approach to ANCA-associated vasculitides.
AB  - Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) include
      Wegener's granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome.
      Given their rarity, protean clinical manifestations, imperfect diagnostic tests,
      and wide differential diagnosis, they pose a diagnostic challenge even to
      experienced clinicians. This article describes diagnostic approaches for patients
      suspected of having one of the ANCA-associated vasculitides. The clinical
      findings at presentation, the role of laboratory and imaging tests, and the
      importance of tissue diagnosis are presented. In each section, issues relevant to
      the differential diagnosis of AAV are discussed.

PMID- 20688244
TI  - Pathogenesis of ANCA-associated vasculitis.
AB  - Antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) comprises a
      group of systemic inflammatory vasculitides associated with circulating
      autoantibodies directed against the neutrophil granule components proteinase 3
      and myeloperoxidase. ANCA interact with their target antigens on cytokine primed
      neutrophils, causing neutrophil activation via several signaling pathways that
      culminates in endothelial interaction, degranulation, cytokine production, and
      endothelial and tissue damage. The presence of autoantibodies implies the
      assistance of autoreactive T-helper cells and B cells, and a failure of
      regulatory mechanisms. This article reviews the current evidence for the
      pathogenic mechanisms culminating in autoantibody production, the effects of ANCA
      neutrophil and neutrophil-endothelial interactions, and the mechanisms of tissue
      damage.

PMID- 20688247
TI  - Clinical manifestations and treatment of Wegener's granulomatosis.
AB  - Wegener's granulomatosis (WG) is characterized by granulomatous lesions and
      vasculitic disease manifestations. Granulomatous lesions are found in the upper
      and lower respiratory tract (eg, granulomatous sinusitis, orbital masses, and
      pulmonary granuloma), whereas vasculitic manifestations occur frequently in lung
      (alveolar hemorrhage) and kidney (glomerulonephritis). Vasculitis is typically
      associated with antineutrophil cytoplasmic antibodies (ANCA) directed against
      proteinase 3. WG has been traditionally associated with a poor outcome and
      increased mortality as documented by numerous studies; however, recent cohort
      studies report an improved outcome, probably a consequence of increased awareness
      leading to an earlier diagnosis, and to improved treatment strategies derived
      from evidence from controlled trials. Treatment regimens for WG, adapted to
      disease stage and activity, are reviewed and discussed in this article.

PMID- 20688248
TI  - Clinical manifestations and treatment of Churg-Strauss syndrome.
AB  - Churg-Strauss syndrome (CSS) is a systemic necrotizing vasculitis affecting small
      to medium-sized vessels, and characterized by asthma, blood hypereosinophilia,
      and eosinophil-rich granulomatous inflammation of the respiratory tract. In the
      past few years the pathogenesis of the disease and its clinical manifestations
      have been clarified, fostering important advances in the treatment of CSS.
      Systemic corticosteroids are still considered the cornerstone of treatment. Many
      issues need to be addressed, such as how to maintain remission, prevent disease
      relapses, and treat refractory disease. This review provides a clinical overview
      of CSS and a summary of the current treatments and novel therapies.

PMID- 20688250
TI  - Pauci-immune necrotizing glomerulonephritis.
AB  - Pauci-immune necrotizing glomerulonephritis is the most frequent cause of rapidly
      progressive glomerulonephritis and, in most cases, is associated with
      antineutrophil cytoplasmic antibodies (ANCA). It is either the renal
      manifestation of Wegener's granulomatosis, microscopic polyangiitis of Churg
      Strauss syndrome, or a renal-limited vasculitis. In this review, the
      histopathologic changes seen in renal biopsies of patients with pauci-immune
      glomerulonephritis are described. The authors also describe why the disease is
      sometimes limited to the kidneys, the clinical course of renal disease, treatment
      issues, how to deal with disease relapses, and how to prevent them from
      occurring. Furthermore, the necessity of renal biopsy and rebiopsy, the
      usefulness of rapid ANCA detection at diagnosis, and serial measurement of ANCA
      during follow-up are discussed. The effect of dialysis on the disease process and
      the possibility of renal transplantation after disease remission are also
      debated.

PMID- 20688249
TI  - Microscopic polyangiitis.
AB  - In 1923, Friedrich Wohlwill described two patients with a "microscopic form of
      periarteritis nodosa," which was distinct from the classical form. This disease,
      now known as microscopic polyangiitis (MPA), is a primary systemic vasculitis
      characterized by inflammation of the small-caliber blood vessels and the presence
      of circulating antineutrophil cytoplasmic antibodies. Typically, microscopic
      polyangiitis presents with glomerulonephritis and pulmonary capillaritis,
      although involvement of the skin, nerves, and gastrointestinal tract is not
      uncommon. Treatment of MPA generally requires use of a cytotoxic agent (such as
      cyclophosphamide) in addition to high-dose glucocorticoids. Recent research has
      focused on identifying alternate treatment strategies that minimize or eliminate
      exposure to cytotoxic agents. This article reviews the history, pathogenesis,
      clinical manifestations, and treatment of MPA.

PMID- 20688251
TI  - Ocular manifestations of ANCA-associated vasculitis.
AB  - The antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides-Wegener's
      granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome-can present
      with various ophthalmic manifestations. In a subset of patients, these findings
      may be the earliest indicators of systemic disease. Orbital and anterior segment
      findings are most common, whereas posterior segment complications such as retinal
      vasculitis and optic neuropathy occur much less frequently. This article
      describes the distinguishing features of associated ophthalmic disease, focusing
      on the manifestations clinicians are most likely to encounter and those with the
      most significant ocular morbidity. Although the ANCA-associated vasculitides
      require systemic workup and treatment, this article discusses diagnostic and
      therapeutic modalities often used concurrently for ophthalmic disease.

PMID- 20688252
TI  - Outcome measures in ANCA-associated vasculitis.
AB  - The outcome in patients with antineutrophil cytoplasm antibody (ANCA)-associated
      vasculitis has considerably improved with the use of potent immunosuppression. In
      the most severe cases, mortality remains an important risk despite aggressive
      intervention. However, for most patients who survive, quality of survival is
      affected by morbidity due to low-grade disease activity, episodes of relapse,
      damage from the effects of disease and its treatment, development of associated
      comorbidity, and the social and psychological problems of chronic disease. A
      rational approach to management of patients with ANCA-associated vasculitis
      requires careful measurement of these different facets of disease, so that
      treatment is appropriate. This article reviews the development of assessment
      tools used to quantify disease in vasculitis, which have been extensively used in
      clinical trials and are also appropriate for use in individual patient care.

PMID- 20688253
TI  - The future of ANCA-associated vasculitis.
AB  - The introduction of cyclophosphamide for treatment and the detection of
      antineutrophil cytoplasmatic antibodies (ANCA) as a seromarker for ANCA
      associated vasculitis (AAV) have been the most important milestones in the
      history of AAV. Nevertheless, there are still many issues to resolve to fully
      understand the pathogenesis of AAV and to improve patient outcomes. There is a
      need for diagnostic criteria; treatment strategies need further improvement to
      reduce the toxicity of conventional immunosuppressants such as cyclophosphamide.
      The elucidation of the genetic background in patients with AAV and the role of
      granulomatous lesions found in Wegener's granulomatosis are required to fully
      understand the pathophysiology of AAV.

PMID- 20688255
TI  - Armadillo-repeat protein functions: questions for little creatures.
AB  - Armadillo (ARM)-repeat proteins form a large family with diverse and fundamental
      functions in many eukaryotes. ARM-repeat proteins have largely been characterised
      in multicellular organisms and much is known about how a subset of these proteins
      function. The structure of ARM-repeats allows proteins containing them to be
      functionally very versatile. Are the ARM-repeat proteins in 'little creatures' as
      multifunctional as their better-studied relatives? The time is now right to start
      analysing ARM-repeat proteins in these new systems to better understand their
      cell biology. Here, we review recent advances in understanding the many cellular
      roles of both well-known and novel ARM-repeat proteins.

PMID- 20688254
TI  - Maternal dietary fat intake during gestation and lactation alters tissue fatty
      acid composition in the adult offspring of C57Bl/6 mice.
AB  - We investigated the effects of maternal dietary fat intake during gestation and
      lactation on the tissue fatty acid composition of the adult offspring. Female
      C57Bl/6 mice were fed high fat diets enriched with lard or safflower oil or chow
      during mating, gestation and lactation. The offspring obtained from each group of
      mothers were continued on diets rich in lard, safflower oil or chow post-weaning
      until 11 weeks of age. Livers and hearts were collected for fatty acid analysis.
      A maternal diet rich in safflower oil was associated with enrichment of hepatic
      tissue with n-3 polyunsaturated fatty acids in the offspring fed chow post
      weaning compared to the offspring fed chow throughout. However, a continuous
      exposure to a safflower oil- as well as lard-rich diet during the pre- and post
      weaning time periods was associated with reduced content of docosahexaenoic acid
      in both liver and heart tissues compared to the offspring fed chow throughout. In
      conclusion, this study demonstrated lasting effects of maternal dietary fat
      intake, as well as an interaction between pre- and post-weaning diets, on the
      tissue fatty composition in adult offspring.

PMID- 20688256
TI  - Effectiveness of subcutaneous injections of a cartilage preparation in
      osteoarthritis of the knee--a randomized, placebo controlled phase II study.
AB  - OBJECTIVES AND METHODS: Articulatio Genus D5 (AG5), a cartilage preparation, is
      widely used within anthroposophic medicine to treat osteoarthritis of the knee
      (OA). To evaluate its efficacy 91 OA patients were randomized to receive either
      AG5 (46) or placebo (45) following a fully sequential study design. For a period
      of 4 weeks AG5 or placebo were injected subcutaneously 3 times a week in the
      predominantly affected knee. Outcome parameters were the Western Ontario and Mc.
      Masters University Arthritis Index (WOMAC) scores and the use of concomitant pain
      medication during a follow up period of 2 months. RESULTS: 89 patients completed
      the study. After 4 weeks of treatment WOMAC pain scores were significantly
      reduced compared to baseline (mean from 5.1+/-1.8 to 3.2+/-2.2 with AG5 and from
      4.3+/-1.5 to 3.0+/-1.8 with placebo, p<0.001) in both groups. This effect was
      maintained until follow up (mean 3.3+/-2.6 with AG5 and 3.2+/-2.4 with placebo).
      WOMAC function- and stiffness scores and use of concomitant pain medication were
      also significantly reduced. There was, however, no significant difference between
      AG5 and placebo (group difference after 4 weeks: -3.3, CI: -11.8 to 5.3, p=0.46,
      triangular test). After follow up, WOMAC scores were also not different between
      AG5 and placebo but the use of pain medication dropped significantly more in the
      AG5 group (p=0.036). Severe side effects did not occur, minor side effects in 2
      patients (1 in each group) were related to the subcutaneous injection.
      CONCLUSIONS: For the primary outcome parameter pain AG5 was not superior to
      placebo after 4 weeks of treatment but the equal reduction of pain in combination
      with higher reduction of pain medication suggests an effect of the preparation.
      The long term effect of AG5 on sparing pain medication should be further
      investigated.

PMID- 20688257
TI  - Participating in and delivering the ATEAM trial (Alexander technique lessons,
      exercise, and massage) interventions for chronic back pain: A qualitative study
      of professional perspectives.
AB  - OBJECTIVES: To outline professionals' experiences of participation, perceived
      benefits and acceptability of the interventions delivered in the ATEAM trial
      (Alexander technique lessons, exercise, and massage), for patients with chronic
      or recurrent back pain. DESIGN: Qualitative study using in-depth interviews was
      conducted with a purposeful sample of twenty professionals (general practitioners
      (GPs), nurses, Alexander technique teachers, and massage therapists). Data were
      recorded, transcribed, and analysed thematically using the constant comparison
      method. RESULTS: Evidence of effectiveness GPs wanted an evidence base for the
      interventions, whilst nurses, Alexander technique teachers and massage therapists
      perceived patient reports of benefit as evidence. Professionals' perception of
      the acceptability of the intervention: professional perspectives differed, with
      GPs and nurses viewing the structured nature of exercise prescription and
      Alexander technique lessons as more beneficial and acceptable than massage in
      alleviating patients' back pain. Economic cost: the cost to patients pursuing
      Alexander technique lessons and massage was perceived to be a barrier outside the
      trial. Inter-professional communication: there was little communication between
      the professionals groups within the trial. CONCLUSIONS: Valuable insights have
      been gained into the perceived benefits and acceptability of exercise, Alexander
      technique lessons and massage as interventions for chronic back pain. Lessons in
      the Alexander technique with or without exercise, was perceived as more
      beneficial and acceptable than massage by professionals who participated and
      delivered the ATEAM trial interventions.

PMID- 20688258
TI  - The use of complementary and alternative medicine by patients attending a UK
      headache clinic.
AB  - OBJECTIVES: This study was undertaken in order to determine the extent of the use
      of CAM in a UK headache clinic. DESIGN: Ninety-two patients attending a headache
      clinic were given a questionnaire containing questions regarding their headaches
      and their use of CAM for headaches. SETTING: Outpatient headache clinic,
      Birmingham, UK. Main outcome measures. The use of complementary and alternative
      therapies and predictive factors. RESULTS: 32% of respondents had used a median
      of 3 different CAM therapies for their headache. The commonest source of
      recommendation of CAM use was a friend or relative (72%) and the commonest reason
      given for using CAM was as a last resort after trying all conventional therapies
      offered (48%). CAM therapies were perceived as beneficial by 60% of CAM users and
      no users perceived the CAM therapy to worsen their headache. 42% of CAM users had
      not disclosed it to their doctor or nurse, 80% of these giving the reason that
      the doctor or nurse never asked, rather than fear of discouragement or lack of
      understanding. Individuals who were in employment were more likely to have used
      CAM than those who were not. Binary logistic regression revealed Headache Impact
      Test (HIT-6) score to be a significant predictor of CAM use (Odds Ratio=1.38 [95%
      CI 1.05-1.81]). CONCLUSIONS: As a matter of desperation, headache clinic patients
      try CAM therapies. Health care professionals involved in the management of
      headache should be aware of this. There is a need for evaluation of the benefits
      and safety of CAM therapies for headache.

PMID- 20688259
TI  - Barriers to patient referral for Complementary and Alternative Medicines and its
      implications on interventions.
AB  - AIM: To study the perceptions of Complementary and Alternative Medicine (CAM)
      among healthcare professionals and identify factors associated with referral for
      CAM treatment. METHODS: An anonymous, self-administered survey was conducted in
      April 2008. All doctors, registered nurses, physiotherapists and occupational
      therapists in Tan Tock Seng Hospital were invited to participate. Data were
      analysed using SPSS v15. RESULTS: The overall response rate was 61.9%. Most
      respondents perceived their knowledge of CAM to be limited and had little
      personal experiences with CAM. Few had referred a small percentage of their
      patients for CAM therapies. Nonetheless, 62.2% of respondents believed that CAM
      would be safe when practiced by trained professionals and only 6.5% agreed that
      physicians should warn patients against CAM. Respondents who did not refer
      patients for CAM therapy cited lack of personal knowledge on the subject (53.4%);
      not knowing a suitable CAM practitioner (29.0%); and not thinking it was
      necessary (14.6%). The key reasons for referring were patients' preferences
      (58.0%); efficacy of CAM for specific conditions (39.1%); and when other
      treatment modalities were unsuccessful (21.9%). Most respondents (82.7%) had
      favourable attitudes and expressed interest in attending CAM seminars.
      CONCLUSION: The majority of western-trained healthcare professionals perceived
      their knowledge of CAM to be low. Most referrals to CAM were made because their
      patients believed in CAM. Limited personal knowledge and experiences were
      associated with lower referrals. However, they were interested to know about the
      common CAM modalities. This suggests the need for more CAM education
      interventions for healthcare professionals.

PMID- 20688260
TI  - Is acupuncture an acceptable option in stroke rehabilitation? A survey of stroke
      patients.
AB  - OBJECTIVE: Stroke is a leading cause of morbidity and mortality and stroke
      survivors make up the largest group of patients in rehabilitation. These
      individuals also have one of the longest lengths of stay in rehabilitation. It
      has been suggested that acupuncture may be beneficial in post-stroke
      rehabilitation and in this study we examine how stroke patients value acupuncture
      and their perceptions of acupuncture as a rehabilitation treatment option. DESIGN
      AND SETTING: A questionnaire was distributed to individuals undergoing post
      stroke rehabilitation at three rehabilitation centers attached to hospitals in
      Toronto, Canada. RESULTS: Two hundred and seventy-three individuals completed the
      questionnaire with the respondent group comprising mainly males (62%) over 65
      years of age (68%). Overall 29% had used acupuncture with 16% receiving
      acupuncture treatment for stroke related conditions. Almost all respondents (98%)
      wanted to know more about acupuncture in stroke rehabilitation and 87% would
      consider acupuncture as a treatment option. Few (8%) reported that they had
      advanced level knowledge about acupuncture, with most reporting a basic (48%) or
      intermediate (33%) level which recognized that acupuncture used fine needles to
      produce a therapeutic response. Those with prior acupuncture experience expected
      to pay more for treatment. The main factors influencing decisions to use
      acupuncture were practitioner competency (84%), cost (65%) and sterilization
      concerns (40%). CONCLUSION: This study demonstrates that there is willingness by
      patients attending conventional hospital-based rehabilitation centers to consider
      acupuncture in stroke rehabilitation and that lack of knowledge about this
      treatment is not a barrier to use.

PMID- 20688261
TI  - Effects of music on depression and sleep quality in elderly people: A randomised
      controlled trial.
AB  - OBJECTIVES: To determine the effect of music on sleep quality in elderly people.
      In addition, we aimed to examine if there were effects on vital signs and
      depression levels. BACKGROUND: Sleep disturbances and depression are common in
      older people, and their impacts on this group, along with its conventional
      treatment, merit our attention as our population ages. Conventional
      pharmacological methods might result dependence and impairment in psychomotor and
      cognitive functioning. Listening to music, which is a non-pharmacological method,
      might reduce depression and promote sleep quality. DESIGN: A randomised
      controlled study was conducted during the period December 2006 to January 2007.
      SETTING: At participants' homes in Hong Kong. PARTICIPANTS: In total, 42 elderly
      people (21 using music and 21 controls) completed the study after being recruited
      in one community services centre. INTERVENTION: Participants listened to their
      choice of music for 30min per week, for 4 weeks. MAIN OUTCOME MEASURES: Blood
      pressure, heart rate, depression levels and sleep quality variables were
      collected once a week for 4 weeks. RESULTS: In the experimental group, there were
      statistically significant reductions in geriatric depression scores and sleep
      quality at week 4. In the control group, there were no statistically significant
      reductions in depression and improvement of sleep quality over the 4 weeks.
      However, for all the outcome measures, no significant differences were found
      between groups over the 4 weeks. CONCLUSIONS: The findings contribute to
      knowledge about the effectiveness of soft slow music used as an intervention to
      improve depression and sleep quality in elderly people. Whilst there were no
      statistical differences between groups, there was some indication that music
      yielder higher improvement on some of the parameters, which are worthy of further
      investigation in larger trials.

PMID- 20688262
TI  - An overview of art therapy interventions for cancer patients and the results of
      research.
AB  - OBJECTIVES: Over the last few years several offers in- and outpatient creative
      therapy interventions for cancer patients have been developed, implemented and
      researched. This article describes the content, concept and structure of art
      therapy interventions based on painting or drawing as well as some further
      methodical procedures and research results of art therapy in the field of psycho
      oncology. METHODS: We searched electronic databases for papers published between
      1987 and March 2009 on painting or drawing based art therapy interventions in
      oncology. The papers were selected using the inclusion criteria detailed below.
      RESULTS: Of 56 retrieved manuscripts, 17 papers reporting 12 research projects
      were included. The art therapy interventions differ from each other considerably
      in their content and structure. The variance in the study design of the papers
      was also high. More females than males participated in the interventions. The
      papers dealt with a variety of questions. A total of seven quantitative papers
      focused on mental health. A decrease in anxiety and depression was noted in six
      of these. Three papers documented an increase in quality of life. Moreover, four
      qualitative papers indicated positive effects on personal growth, coping, the
      development of new form of self-expression, and social interaction. Three papers
      with qualitative methods investigated participants' mechanisms for coping with
      their disease. CONCLUSION: Published papers show that art therapy benefits cancer
      patients in various ways including improving their mental health. Nevertheless,
      more studies with an evidence-based design are necessary for reaching further
      conclusions on efficacy of art therapy. This research should include a focus on
      gender differences, and controlling possible influencing factors.

PMID- 20688263
TI  - Fish oil supplementation increases the cyclooxygenase inhibitory activity of
      paracetamol in rheumatoid arthritis patients.
AB  - OBJECTIVE: To examine interactions between fish oil and paracetamol for
      inhibition of prostaglandin synthesis in patients with rheumatoid arthritis (RA).
      METHODS: Patients from an early RA clinic who were treated with a standardized
      combination DMARD regimen were enrolled. They were advised to consume an anti
      inflammatory dose of fish oil containing the n-3 fatty acid, eicosapentaenoic
      acid (EPA), or a comparator oil. High EPA and Low EPA groups were defined by
      blood EPA levels >3.5% or <2%, respectively, of plasma phospholipid fatty acids.
      Participants provided a blood sample before, and 1h after ingestion of 1g
      paracetamol. The blood was incubated in different ways to allow measurement of
      COX-2 generated prostaglandin E(2) (PGE(2)) and COX-1 generated thromboxane A(2)
      (TXA(2)). RESULTS: Paracetamol suppressed the eicosanoid measures of COX-1 and
      COX-2 activities and the suppression was greater in the High EPA group. The
      results indicate that the combination of fish oil and paracetamol suppresses
      PGE(2) synthesis by an amount equivalent to that from maximum therapeutic doses
      of NSAIDs. CONCLUSION: Paracetamol is recommended for first-line use ahead of
      NSAIDs for symptom relief in RA or OA. Combining paracetamol with fish oil will
      enhance suppression of nociceptive PGE(2) synthesis and thereby may provide
      additive symptomatic benefits.

PMID- 20688265
TI  - [XXXVI National congress of the SEEIUC, Malaga 2010].

PMID- 20688264
TI  - Astrocytes derived from fetal neural progenitor cells as a novel source for
      therapeutic adenosine delivery.
AB  - PURPOSE: Intracerebral delivery of anti-epileptic compounds represents a novel
      strategy for the treatment of refractory epilepsy. Adenosine is a possible
      candidate for local delivery based on its proven anti-epileptic effects. Neural
      stem cells constitute an ideal cell source for intracerebral transplantation and
      long-term drug delivery. In order to develop a cell-based system for the long
      term delivery of adenosine, we isolated neural progenitor cells from adenosine
      kinase deficient mice (Adk(-/-)) and compared their differentiation potential and
      adenosine release properties with corresponding wild-type cells. METHODS: Fetal
      neural progenitor cells were isolated from the brains of Adk(-/-) and C57BL/6
      mice fetuses and expanded in vitro. Before and after neural differentiation,
      supernatants were collected and assayed for adenosine release using liquid
      chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: Adk(-/-) cells
      secreted significantly more adenosine compared to wild-type cells at any time
      point of differentiation. Undifferentiated Adk(-/-) cells secreted 137+/-5 ng
      adenosine per 10(5) cells during 24 h in culture, compared to 11+/-1 ng released
      from corresponding wild-type cells. Adenosine release was maintained after
      differentiation as differentiated Adk(-/-) cells continued to release
      significantly more adenosine per 24 h (47+/-1 ng per 10(5) cells) compared to
      wild-type cells (3+/-0.2 ng per 10(5) cells). CONCLUSIONS: Fetal neural
      progenitor cells isolated from Adk(-/-) mice--but not those from C57BL/6 mice-
      release amounts of adenosine considered to be of therapeutic relevance.

PMID- 20688266
TI  - [Identity of gender and intensive care: influence of masculinity and femininity
      in the perception of nursing care].
AB  - INTRODUCTION: Nursing has essentially been the work of women. The increase in men
      incorporating into nursing makes us think about whether there are different ways
      of expressing and practicing a profession in relationship to gender. OBJECTIVE:
      To describe if there are different ways of perceiving and assessing ICU work from
      a gender perspective. METHODOLOGY: A qualitative phenomenological study. SAMPLE:
      6 male nurses and 6 female nurses from the ICU of the Hospital Universitario de
      Bellvitge (HUB). DATA COLLECTION: In-depth semi-constructed interview. Content
      analysis. RESULTS: Male nurses describe ICU work in terms of autonomy in making
      decisions and professional competence. They claim responsibility for their
      identity as nurses and stress the low social recognition of the profession. They
      prioritize the responsibility of decision making over the final outcome and
      evaluate family satisfaction in terms of prestige and competence. They are more
      practical. Female nurses describe the work in terms of control and follow-up of
      the patient's evolution. They emphasize the final care outcome and evaluate
      satisfaction in terms of a relationship of confidence and warm patient care. They
      are more meticulous. CONCLUSIONS: There are differences in how they classify
      their ICU work, in the self-evaluation of professional identity, behavior in the
      development of the nursing care and in perception of family satisfaction. No
      differences are observed regarding problem solving with the technology.

PMID- 20688267
TI  - Bad month for cancer care in the UK.

PMID- 20688268
TI  - How can we tell if PET imaging for cancer is cost effective?

PMID- 20688269
TI  - Building research capacity and clinical trials in developing countries.

PMID- 20688270
TI  - GPC5 rs2352028 variant and risk of lung cancer in never smokers.

PMID- 20688271
TI  - GPC5 and lung cancer in multiple sclerosis.

PMID- 20688273
TI  - The importance of platform annotation in interpreting microarray data.

PMID- 20688274
TI  - Clinical implementation of the intrinsic subtypes of breast cancer.

PMID- 20688275
TI  - The importance of gene-centring microarray data.

PMID- 20688277
TI  - Evolutionary genomics of C4 photosynthesis in grasses requires a large species
      sampling.
AB  - Recent advances in genomics open promising opportunities to investigate adaptive
      trait evolution at the molecular level. However, the accuracy of comparative
      genomic studies strongly relies on the taxonomic coverage, which can be
      insufficient when based solely on a few completely sequenced genomes. In
      particular, when distantly-related genomes are compared, orthology of some genes
      can be misidentified and long branches of the phylogenetic reconstructions make
      inappropriate positive selection tests, as recently exemplified with
      investigations on the evolution of the C(4) photosynthetic pathway in grasses.
      Complementary studies addressing the diversification of multigene families in a
      broad taxonomic sample can help circumvent these issues.

PMID- 20688278
TI  - In vitro interactions between bone marrow stromal cells and hippocampal slice
      cultures.
AB  - Bone marrow stromal cells (BMSCs) are capable of differentiating into various
      cell types including brain cells. Several groups have also demonstrated trophic
      effects of MSC grafts in experimental ischemia models. However, the underlying
      molecular mechanisms of these effects are not fully understood. We developed an
      "in vitro graft model" which consisted in a coculture of GFP-expressing BMSCs and
      hippocampal organotypic slice cultures. Total marrow cells (MCs) or BMSCs after
      one (BMSC(1P)) or five passages (BMSC(5P)) were transplanted on hippocampal
      slices. During the 10 days of our experiments, MCs and BMSC(1P) migrated toward
      the tissue, but their total number remained constant. Conversely, the number of
      BMSC(5P) decreased over the 10 days of the experiment, and no migration could be
      detected. Using immunohistochemistry, we observed that the hippocampal slices
      induced the expression of neural antigens in very few grafted cells, but MCs and
      BMSC(1P) improved the conservation of the hippocampal slice culture. Similar
      experiments using BMSC(5P) did not produce any significant change. We conclude
      that the number of passages greatly influence BMSCs survival rate, migration and
      neuroprotective capacities.

PMID- 20688279
TI  - [Evaluation of androstenedione adrenal content and effects of castration on the
      domestic rabbit (Oryctolagus cuniculus)].
AB  - DHEA, DHEA sulphate and androstenedione are C19 steroids secreted by the adrenal
      cortex. These hormones with a weak androgen activity are precursors of estrogens
      and androgens. In human and other primates these hormones are produced in
      important quantities, even though, in domestic and laboratory animals, a few
      secretion is measured. In this survey, the androstenedione is quantified both in
      plasma and adrenal gland of young, prepubertal and adult rabbits and the
      castration effects on adrenal cortex histology are noted too. The absolute weight
      (AW) of the left adrenal gland is slightly higher than the right (p>0.05) for all
      animals and the gland absolute weight (AW) for the adult rabbit is superior to
      the young and prepubertal rabitts (p<0.05). The castration effect in adult
      increases the adrenal weight (p<0.001). A zonation of adrenal cortex for young
      rabbits is observed. The zona fasciculata is important for young and prepubertal
      rabbits whereas, the zona reticularis is thicker for the adults. Thickness of
      glomerulosa, fasciculata and reticularis zonas increased with 6.55% (p>0.05),
      15.9% (p<0.01) and 79.21% (p<0.001) for the castred adult rabbits and
      histological modifications were observed in the zona reticularis. The plasma
      androstenedione is negligible for the young (0.060+/-0.01 ng/mL), weak for the
      prepubertal (0.152+/-0.03 ng/mL) and reaches (0.263+/-0.03 ng/mL) for the adult.
      The androstenedione relative content (ng/100 mg of adrenal weight) is 2.90+/
      0.30; 4.54+/-0.82 and 1.34+/-0.36 for the young, prepubertal and adult rabbits.
      In this work, an increase of the androstenedione adrenal content is observed for
      the prepubertal rabbits, which could intervene in the process of puberty.

PMID- 20688280
TI  - Chromium stress in paddy: (i) nutrient status of paddy under chromium stress;
      (ii) phytoremediation of chromium by aquatic and terrestrial weeds.
AB  - A field experiment was conducted with paddy (Oryza sativa L.) irrigated with
      different concentrations (Control, 2.5, 5, 10, 25, 50, 75, 100 and 200 mg/l) of
      chromium. The changes in growth, yield, nutrient content and chromium
      accumulation in the paddy are reported. The growth of shoot, root, total leaf
      area, fresh weight, dry weight and yield of the paddy gradually decreased with
      increasing Cr concentration. Similarly, the uptake of macronutrients (N, P, K)
      and micronutrients (Mn, Cu, Zn, Fe) were also gradually decreased. However, the
      chromium accumulation gradually increased with the increasing concentrations of
      chromium. Among the aquatic plants tested, Eicchornia crassipes showed better
      performance in accumulating higher amount of chromium. Similarly, certain grasses
      and weeds such as Cyperus rotundus, Cyperus kylinga, Marselia quadrifolia and
      Ludwigia parvifloria were used for the phytoremediation of chromium polluted
      soil. Among them, Cyperus rotundus accumulated higher amount of chromium than the
      other plants tested.

PMID- 20688281
TI  - HIV-1 infection: functional competition between gp41 and interleukin-2.
AB  - To determine whether the gp41 of HIV-1 could adhere to the interleukin (IL)-2
      receptor at the surface of target cells in vitro, we analysed in vitro the
      possible functional competition between various forms of the HIV-1 gp41 molecule
      (i.e. peptides, trimeric or primary structures) and IL-2. This competition has
      been analysed in a test involving the proliferation of an IL-2-dependent cell
      line (CTLL2). The putative interaction between the IL-2 molecule and HIV-1 has
      also been assayed on MT4 cells (CD4(+) T lymphocytes) in culture. The gp41
      trimeric molecule and an HIV-1 gp41 peptide (578-590 aminoacid sequence)
      dramatically inhibited CTLL2 cell proliferation, despite the presence of IL-2.
      The addition of serum, containing anti-gp41 antibodies, from HIV-1 patients
      resulted in a significant abolition of this inhibition. The concomitant
      incubation of IL-2 and HIV-1 with MT4 cells resulted in a strong decrease (70%)
      in HIV-1 p24 release. These data suggest that the gp41 of HIV-1 can use the IL-2
      receptor during the process of HIV-1 infection and that there is some functional
      mimesis between gp41 and IL-2.

PMID- 20688282
TI  - Biological influences on inter- and intraspecific isotopic variability among
      paired chondrostome fishes.
AB  - This study aimed at examining resource partitioning both at the inter- and
      intraspecific levels between paired chondrostome fishes: Chondrostoma nasus, the
      nase, C. toxostoma, the sofie, and their hybrid. The study was performed in the
      south of France and concerned a main river (the Durance River) and a tributary
      (the Buech River). In these rivers, C. nasus was an introduced species,
      originating in central Europe, and C. toxostoma was an endemic congener, in the
      south of France. Stable isotope analysis was used to analyse trophic and spatial
      niches. Isotopic differences indicated that individuals from the three taxa (C.
      nasus, C. toxostoma and their hybrid) have different spatial origins. At the
      interspecific level, the different chondrostomes originating from the Buech River
      showed a high level of trophic niche overlap. At the intraspecific level, nase
      individuals originating from the different spatial origins showed a resource
      polymorphism; differences in morphology were associated with variation in
      behaviour and life history traits. Their coexistence was a likely outcome of
      resource polymorphism. This study provides an example of the importance of
      considering the link between intra- and interspecific interactions to gain an
      understanding of the mechanisms driving the coexistence of species-pairs.

PMID- 20688283
TI  - Cedrus libani (A. Rich) distribution in Lebanon: past, present and future.
AB  - Long-term vegetation studies are needed to better predict the impact of future
      climate change on vegetation structure and distribution. According to the IPCC
      scenario, the Mediterranean region is expected to undergo significant climatic
      variability over the course of this century. Cedrus libani (A. Rich), in
      particular, is currently distributed in limited areas in the Eastern
      Mediterranean region, which are expected to be affected by such climate change.
      In order to predict the impact of future global warming, we have used fossil
      pollen data and model simulations. Palaeobotanical data show that C. libani has
      been affected by both climate change and human activities. Populations of C.
      libani survived in refugial zones when climatic conditions were less favourable
      and its range extended during periods of more suitable climate conditions.
      Simulations of its future geographical distribution for the year 2100 using a
      dynamic vegetation model show that only three areas from Mount Lebanon may allow
      its survival. These results extrapolated for cedar forests for the entire Eastern
      Mediterranean region show that forests in Syria are also threatened by future
      global warming. In southern Turkey, cedar forests seem to be less threatened.
      These results are expected to help in the long-term conservation of cedar forests
      in the Near East.

PMID- 20688284
TI  - Buthid scorpions found in caves; a new species of Isometrus Ehrenberg, 1828
      (Scorpiones, Buthidae) from southern Vietnam.
AB  - A new species, Isometrus (Reddyanus) deharvengi sp. n., is described from caves
      of the region of Hon Chong, Kien Giang in southern Vietnam. Comments are also
      added about the scorpion fauna of Southeast Asia and cave dwelling buthid
      scorpions.

PMID- 20688285
TI  - Immunopotentiation of hepatitis B vaccine using biodegradable polymers as an
      adjuvant.
AB  - BACKGROUND/PURPOSE: The purpose of this research was to develop an alternative
      adjuvant for hepatitis B vaccine (HBsAg) that elicits a long-lasting immune
      response after a single administration. In this study, the suitability of Poly
      (D, L)-lactide-co-glycolic acid (PLGA), Poly lactic acid (PLA) and Chitosan
      polymers as adjuvants for HBsAg were investigated. METHODS: We used solvent
      evaporation and emulsion cross-linking techniques to encapsulate HBsAg into the
      different polymeric systems. The newly developed microparticles were evaluated
      for vaccine content, particle size distribution, in vitro release and
      immunogenicity. RESULTS: HBsAg-encapsulated PLGA and PLA microparticles were
      smooth and spherical. However, Chitosan microparticles were homogeneous, and
      almost spherical, with rough surfaces. The vaccine loading and release patterns
      varied with the type of polymer used. In this study, Chitosan polymeric
      microparticles released antigen until day 63 post-injection; however, the release
      period of the PLGA and PLA systems was shorter. A significant increase in the
      level of antibodies to HBsAg was induced by all the polymeric microparticles.
      CONCLUSION: The results indicate that Chitosan microparticles are a more
      efficient adjuvant for HBsAg than PLGA and PLA polymeric microparticles.

PMID- 20688286
TI  - An outbreak of coxsackievirus A16 infection: comparison with other enteroviruses
      in a preschool in Taipei.
AB  - BACKGROUND/PURPOSE: The transmission rate of enteroviruses in young children
      remains unclear. Therefore, we carried out active surveillance in preschool
      children to investigate the transmission rate and clinical manifestation of
      enteroviruses. METHODS: From September 2006 to December 2008, we monitored
      infectious diseases in children 2(-3 years of age) in a preschool in Taipei. If
      any child had a febrile illness or symptoms/signs of enteroviral infection [e.g.
      herpangina or hand-foot-and-mouth disease (HFMD)], we performed viral isolation
      and enterovirus polymerase chain reaction. VP1 sequencing was performed to define
      their serotypes. We also collected clinical data and analyzed transmission rates.
      RESULTS: There were eight episodes of enterovirus infection during the study
      period. The serotypes included coxsackievirus A4 (CA4), CA2 and CA16. The
      transmission rates of CA4 and CA2 among children in same class were 26% and 35%,
      respectively. Between November 28 and December 12, 2008, 13/21 (61.9%) children
      contracted herpangina and/or HFMD. The average age was 2.82 (range, 2.43-3.39)
      years. CA16 was detected in 10/13 (76.9%) of the throat swabs by polymerase chain
      reaction VP1 genotyping. Compared with previous CA2 and CA4 outbreaks, CA16 had a
      significantly higher transmission rate (p = 0.035) and resulted in more cases of
      HFMD (p < 0.001). The transmission duration of coxsackie A viruses within the
      same class ranged from 12 to 40 days. CONCLUSION: Compared with CA2 and CA4, CA16
      infections resulted in more cases of HFMD and had significantly higher
      transmission rates in preschoolers.

PMID- 20688287
TI  - Non-Hodgkin's lymphoma in patients with human immunodeficiency virus infection in
      Taiwan.
AB  - BACKGROUND/PURPOSE: Non-Hodgkin's lymphoma (NHL) is the second most common
      acquired immunodeficiency syndrome-defining malignancy with a high mortality
      rate. This study aimed to describe changes in the incidence and clinical
      characteristics of NHL in human immunodeficiency virus (HIV)-infected patients in
      a referral hospital for HIV care. METHODS: The medical records of HIV-infected
      patients diagnosed with NHL between June 1994 and December 2006 were
      retrospectively reviewed. Risk stratification of each patient was evaluated using
      the International Prognostic Index (IPI). Case patients were followed at least
      for 2 years to assess the 2-year survival rates. RESULTS: During the 12-year
      period, 38 HIV-infected patients were diagnosed with NHL. Their median cluster of
      differentiation 4 count was 82 cells/microL (range, 2-477 cells/microL) at
      diagnosis. Before the introduction of highly active antiretroviral therapy
      (HAART) in April 1997, 9/175 HIV-infected patients (5.1%) developed NHL compared
      with 29/1,386 patients (2.1%) in the HAART era (p < 0.05). Although the 2-year
      survival rate did not differ significantly between patients diagnosed in the pre
      HAART era (22.2%) and those diagnosed in the HAART era (24.1%), patients
      receiving HAART for more than 6 months had better survival rates (p < 0.05). A
      low IPI score was a good prognostic factor predictive of a patient's outcome.
      CONCLUSION: The incidence of NHL in HIV-infected patients declined significantly
      in the HAART era. Despite the introduction of HAART, the short-term survival of
      the patients with NHL remained poor. The IPI was a good predictor for survival.

PMID- 20688288
TI  - Drug resistance pattern of mycobacterium tuberculosis complex at a medical center
      in central Taiwan, 2003-2007.
AB  - BACKGROUND/PURPOSE: Drug-resistant tuberculosis (TB) is an important issue for
      public health. This study was conducted to evaluate the prevalence of drug
      resistance to Mycobacterium tuberculosis complex at Changhua Christian Hospital
      in central Taiwan. METHODS: We retrospectively reviewed 1,961 non-duplicate
      isolates of M. tuberculosis complex from 2003 to 2007. The following data were
      collected: demographic characteristics, previous anti-TB therapy and drug
      susceptibility testing. Antimicrobial drug susceptibility testing was performed
      using the BACTEC MGIT 960 System from January 2003 to February 2005. Starting in
      March 2005, the agar proportion method was used for antimicrobial drug
      susceptibility testing. RESULTS: A total of the 1,961 patients were analyzed. The
      majority (66.5%) of cases were >/= 65 years of age. A total of 151 patients had
      undergone previous anti-TB treatment. Individual drug resistance was as follows:
      229 isolates (11.7%) were resistant to isoniazid, 55 (2.8%) to rifampin, 49
      (2.5%) to ethambutol, and 218 (11.1%) to streptomycin. The overall resistance to
      any drug was 19.1%, while 39 isolates (2.0%) were resistant at least to isoniazid
      and rifampin (multidrug-resistant). A significant decreasing trend in resistance
      rates to the four first-line anti-TB drugs, and any other drug, was observed
      during the 5-year period. Drug resistance was associated with a history of
      previous anti-TB treatment (p = 0.017). CONCLUSION: The study found a significant
      decrease in drug resistance from 2003 to 2007. The multidrug resistance also
      decreased, although this was not statistically significant. This decreasing
      resistance rate may be due to the effect of the direct observed treatment, short
      course strategy which was enhanced in Taiwan after 2006.

PMID- 20688289
TI  - Clinical features and outcomes of spinal tuberculosis in southern Taiwan.
AB  - BACKGROUND/PURPOSE: The early diagnosis and appropriate management of spinal
      tuberculosis (TB) is challenging for clinicians. This study aimed to characterize
      the clinical features and factors affecting treatment outcomes. METHODS: A
      retrospective study of patients with spinal TB over a 7-year period at a medical
      center in southern Taiwan was conducted. Clinical features, underlying diseases,
      laboratory results, imaging findings, therapy, treatment duration and outcomes
      were analyzed. RESULTS: Forty-eight patients (24 men and 24 women) were diagnosed
      with spinal TB. Their mean age was 64.3 years. The most common presenting
      symptoms were backache, neurological deficits, and fever. The most common
      vertebral area involved was lumbar spine (41.7%). The mean number of vertebra
      involved was 2.46. Surgery was carried out on 30 patients (62.5%). Patients who
      had a longer duration of symptoms prior to diagnosis were more likely to have
      surgery (p = 0.03), and patients who received surgery had a more favorable
      outcome (p = 0.063). The mean treatment course was 11.4 +/- 3.7 months. A long
      course treatment did not contribute to favorable outcomes. Twenty-six patients
      had a favorable outcome and 11 had an unfavorable outcome. Factors associated
      with an unfavorable outcome included older age, limb weakness, incontinence,
      spinal kyphotic deformity, and spinal cord compression. CONCLUSION: For elderly
      patients with chronic back pain in Taiwan, the differential diagnosis of spinal
      TB should be considered. Image studies and computed tomography-guided aspiration
      are helpful for early detection. Combined surgical intervention tended to have a
      more favorable outcome and longer treatment periods had no additional benefit.

PMID- 20688290
TI  - Influence of third-generation cephalosporin resistance on adult in-hospital
      mortality from post-neurosurgical bacterial meningitis.
AB  - BACKGROUND/PURPOSE: To investigate the clinical features, etiology and predictors
      of in-hospital mortality in adults with post-neurosurgical bacterial meningitis.
      METHODS: This retrospective analysis included 60 adult patients with culture
      proven post-neurosurgical bacterial meningitis hospitalized between September
      2006 and August 2008. RESULTS: Of the 60 patients, 88.3% had monomicrobial
      infection and 11.7% had mixed infection. The mean duration from the first
      neurosurgical procedure to the diagnosis of meningitis was 21 days (range, 1-134
      days). The median frequency of neurosurgical procedure before meningitis was 1
      (range, 1-5). A total of 69 isolates were identified from the cerebrospinal
      fluid, the most common pathogens were Gram-negative bacilli (43, 62.3%), followed
      by Gram-positive bacteria (24, 34.8%). The three most common Gram-negative
      bacilli were Serratia marcescens (7, 10.1%), Klebsiella pneumoniae (6, 8.7%), and
      Enterobacter cloacae (4, 5.8%). Pseudomonas aeruginosa and Acinetobacter
      baumannii isolates comprised less than 3%. Notably, glucose non-fermenting Gram
      negative bacilli other than Acinetobacter and Pseudomonas spp. accounted for
      11.6% of the total. Of the Gram-negative bacilli, resistance rates to the third
      generation cephalosporins, ceftriaxone and ceftazidime, were 58.1% and 34.9%,
      respectively. The two most common Gram-positive pathogens were Staphylococcus
      aureus (10, 14.5%) and coagulase-negative staphylococci (including S.
      epidermidis) (10, 14.5%). The in-hospital mortality rate was 15.0%, which was
      significantly related to Gram-negative bacilli resistant to third-generation
      cephalosporins in multivariate analysis (adjusted odds ratio = 33.65; p = 0.047).
      CONCLUSION: These findings may portend the spread of serious resistance to third
      generation cephalosporins in nosocomial Gram-negative bacilli throughout the
      neurosurgical units, suggestive of the need to reassess the empirical use of
      third-generation cephalosporins in post-neurosurgical bacterial meningitis.

PMID- 20688291
TI  - Risk factors for bloodstream infections due to extended-spectrum beta-lactamase
      producing Escherichia coli.
AB  - BACKGROUND/PURPOSE: The risk factors for production of extended-spectrum beta
      lactamases (ESBLs) have rarely been studied for bloodstream infections of
      Escherichia coli alone. A case-control study was undertaken to identify the risk
      factors associated with bloodstream infections caused by ESBL producing E. coli.
      METHODS: From January 1, 2005 to June 30, 2007, all patients with a confirmed
      diagnosis of bloodstream infection caused by ESBL-producing E. coli were
      reviewed. Each patient was matched with one control subject who experienced ESBL
      negative E. coli bacteremia during the same study period. RESULTS: Of the 97
      patients diagnosed with ESBL-producing E. coli bacteremia, six were excluded
      owing to incomplete follow-up and missing data. Comparisons were made between 91
      patients and their controls. Multivariate analysis identified urinary
      catheterization [odds ratio (OR) = 6.21, 95% confidence interval (CI) = 1.91
      20.25; p = 0.003], prior exposure to antibiotics (OR = 2.93, 95% CI = 1.18-7.30;
      p = 0.021) and previous treatment with oxyimino-cephalosporins (OR = 5.16, 95% CI
      = 1.03-25.79; p = 0.046) as independent predictors for bloodstream infection by
      ESBL-producing E. coli. Conversely, patients classified as having a community
      acquired infection were less likely to acquire bacteremia caused by ESBL
      producing E. coli than those caused by non-ESBL-producing E. coli (OR = 0.22, 95%
      CI = 0.09-0.57; p = 0.002). CONCLUSION: More judicious use of antimicrobial
      agents, especially oxyimino-cephalosporins, and avoidance of urinary
      catheterization may decrease the possibility of ESBL-producing E. coli bacteremia
      in hospitalized patients.

PMID- 20688292
TI  - In vitro synergistic antimicrobial effect of imipenem and colistin against an
      isolate of multidrug-resistant Enterobacter cloacae.
AB  - BACKGROUND/PURPOSE: Enterobacter cloacae is an important nosocomial pathogen
      responsible for various infections. Little is known about the synergistic effects
      of imipenem and colistin against multidrug-resistant E. cloacae. Therefore, we
      investigated the in vitro effects of imipenem and colistin against a clinical
      isolate of multidrug-resistant E. cloacae. METHODS: A strain of E. cloacae,
      designed Ent 831, was isolated from the sputum of a woman who developed severe
      pneumonia in a medical intensive care unit. Minimal inhibitory concentrations
      (MICs) of imipenem and colistin were determined by the agar dilution method. The
      synergistic effects were investigated using the time-kill method. RESULTS: MICs
      of imipenem and colistin for E. cloacae strain Ent 831 were 0.5 microg/mL and 1.0
      microg/mL, respectively. Using a standard inoculum (5 x 10(5)) CFU/mL), synergism
      was shown with a concentration of two times the MICs of imipenem and colistin.
      Furthermore, four times the MIC of imipenem completely inhibited bacterial growth
      for more than 48 hours, but four times the MICs of colistin resulted in re-growth
      after 4 hours. There was no synergism between imipenem and colistin at two times
      the MICs against a high concentration inoculum (6.24 x 10(6)) CFU/mL).
      Nevertheless, imipenem, with or without colistin, at a concentration of four
      times MICs could inhibit the growth of bacteria for more than 48 hours.
      CONCLUSION: High-dose imipenem, alone or in combination with colistin, is
      effective against multidrug-resistant E. cloacae. Colistin alone, even at a high
      dose, is not effective. However, in vitro susceptibility to antimicrobial
      compounds does not always correlate with clinical success. Thus further testing
      of these antibiotic combinations in animal models is needed in order to predict
      their suitability for clinical use.

PMID- 20688293
TI  - Aerosolized colistin for the treatment of multidrug-resistant Acinetobacter
      baumannii pneumonia: experience in a tertiary care hospital in northern Taiwan.
AB  - BACKGROUND/PURPOSE: Ventilator-associated pneumonia (VAP) due to multidrug
      resistant (MDR) Acinetobacter baumannii in critically ill patients presents an
      emerging challenge to clinicians. Administration of aerosolized colistin as an
      adjunctive therapy is one therapeutic option mentioned in limited evidence-based
      studies. This study aimed to evaluate the effectiveness of adjunctive aerosolized
      colistin treatment for VAP due to MDR pathogens. METHODS: We retrospectively
      reviewed the medical records of patients who had received aerosolized colistin
      for treatment of VAP due to MDR A. baumannii in our hospital from August to
      December 2008. RESULTS: Forty-five patients were enrolled in our study. The mean
      age was 71 +/- 15 years. The mean Acute Physiological and Chronic Health
      Evaluation II (APACHE II) scores on the day of intensive care unit admission and
      on the first day of aerosolized colistin administration were 22.5 +/- 6.7 and
      18.9 +/- 5.7, respectively. The mean duration of intensive care unit stay was 34
      +/- 16 days. The mean daily dosage of aerosolized colistin was 4.29 +/- 0.82
      million IU, and the mean duration of administration was 10.29 days. Seventeen
      patients (37.8%) had a favorable microbiological outcome and 26 (57.8%) showed a
      clinical response. Mortality due to all causes was 42.2%. No adverse effects
      related to inhaled colistin were recorded. CONCLUSION: Aerosolized colistin may
      be considered as an adjunct to intravenous treatments in patients with VAP due to
      colistin-susceptible MDR A. baumannii in critically ill patients.

PMID- 20688294
TI  - Acute community-acquired osteoarticular infections in children: high incidence of
      concomitant bone and joint involvement.
AB  - BACKGROUND/PURPOSE: Pediatric acute osteoarticular infections remain a
      challenging clinical issue for physicians. This paper provides recent clinical
      experiences on acute community-acquired osteoarticular infections in children in
      Taiwan. METHODS: Children with acute community-acquired osteoarticular infections
      admitted to hospital were retrospectively reviewed and the findings compared with
      related infections in Taiwan published during the past 10 years. RESULTS: We
      enrolled 27 children in our study, and reviewed 692 patients reported from six
      major studies in Taiwan. Of the 27 patients, 15 (55.6%) had concomitant bone and
      joint involvement. Blood cultures were positive in 44.4% of the children in this
      study and 48-52% in the other studies. Pathogens could be identified in 66.7% of
      our children and 63-76% in the other studies, when surgical specimens were
      available for culture. Staphylococcus aureus was consistently the most common
      pathogen found in all studies. Of the S. aureus isolates, methicillin-resistant
      S. aureus accounted for 13.3% in our study and 22-24% in the others. CONCLUSION:
      Concomitant osteomyelitis and septic arthritis occurred in over half of our
      patients. The long-term effect of combined bone and joint infection on bone
      growth remains to be determined. Surgical intervention remains an important
      component of management of osteoarticular infections. Our findings are consistent
      with current recommendations of aggressive microbiology diagnosis and initiation
      of empirical monotherapy with oxacillin or oxacillin plus an agent effective
      against Gram-negative bacteria in most cases of community-acquired osteoarticular
      infections.

PMID- 20688295
TI  - Granulocyte colony stimulating factor-induced exacerbation of fungus-related
      immune restoration inflammatory syndrome: a case of chronic disseminated
      candidiasis exacerbation.
AB  - Chronic disseminated candidiasis is a complication of the intensive therapies of
      hematological malignancies revealed during hematopoietic recovery, a context
      reminiscent of the immune restoration inflammatory syndrome in human
      immunodeficiency virus patients receiving antiretroviral therapy. We report a
      case of severe exacerbation of chronic disseminated candidiasis after pegylated
      granulocyte-colony stimulating factor administration. We emphasize the major
      inflammatory substrate of the disease and suggest that immune-modulating
      strategies such as hematopoietic growth factors, should be used cautiously in
      such patients.

PMID- 20688296
TI  - Plesiomonas shigelloides sepsis and meningoencephalitis in a surviving neonate.
AB  - In this study, we report the case of a 2.5-day-old neonate with septicemia and
      meningitis due to Plesiomonas shigelloides. Culture of the cerebrospinal fluid
      showed Gram-negative rods, although the glucose, protein and leukocyte counts
      were normal. The patient was treated with meropenem and survived without any
      sequelae, although we were not able to identify the source of the infection. In
      addition, ten previously reported cases of this infection are reviewed.

PMID- 20688297
TI  - Guidelines on blood cultures.
AB  - Just over one-third of sepsis patients have positive blood cultures, mainly due
      to inadequate sampling volumes (50% of adults have < 1.0 CFU/mL blood) and the
      prior use of antibiotics. However, 20-30% of sepsis patients are given
      inappropriate empirical antibiotics. The Clinical and Laboratory Standards
      Institute guidelines recommend paired culture sets to help discriminate between
      contaminant organisms and true pathogens; four 10-mL bottles (2 sets) should be
      used for the initial evaluation to detect about 90-95% of bacteremias and six 10
      mL bottles (3 sets) should be used to detect about 95-99% of bacteremias. It has
      also been shown that the positivity rate increased by 15-35% with resin-based
      media in patients on antibiotics. For diagnosing catheter-related bloodstream
      infections, differential time-to-positivity is one method recommended to help
      determine whether the catheter is truly the source of infection. The proper
      training of personnel with regard to drawing an appropriate blood volume and the
      importance of clear labeling of culture bottles is also of critical importance.
      Furthermore, if the contamination rate is relatively high, hiring dedicated staff
      who are well-trained in order to get a lower blood culture contamination rate may
      be cost-effective. It is because high false-positive blood culture rates due to
      contamination are associated with significantly increased hospital and laboratory
      charges.

PMID- 20688298
TI  - Evidence-based treatment for advanced germ cell tumor of the testis with a case
      illustration.
AB  - Testicular germ cell tumor is rare in the Asian population. Nevertheless, it is a
      prototypic cancer of young adults because it can be highly malignant but is also
      highly curable, even at an advanced stage. We present a case with far-advanced
      embryonal carcinoma, treated with bleomycin, etoposide and platinum (BEP) x 4
      cycles. This case has shown very good results from the treatment. This is the
      standard therapy for poor- and intermediate-risk patients with germ cell tumors
      in the advanced stage, supported by current evidence-based literature. BEP x 3
      cycles or EP x 4 cycles is the standard therapy for good-risk patients with
      advanced germ cell tumors. Using these treatments, we can achieve durable
      remissions of approximately 90%, 75%, and 45% in good-, intermediate-, and poor
      risk patients, respectively. However, the physical and psychological long-term
      outcomes should be carefully monitored.

PMID- 20688299
TI  - The inverse relationship between body mass index and the presence of a
      varicocele: an interesting epidemiological finding.

PMID- 20688300
TI  - Immunoglobulin G antibody against Helicobacter pylori is an accurate test for
      atrophic gastritis.
AB  - BACKGROUND: Enzyme-linked immunosorbent assay (ELISA) is the most commonly used
      serologic test for Helicobacter pylori. This study aimed to investigate the
      effects of age and atrophic gastritis on the diagnostic accuracy of an
      immunoglobulin G (IgG) antibody test against H. pylori in adults. METHODS: One
      hundred and seventy dyspeptic patients (age range, 20-70 years) were evaluated.
      H. pylori infection was diagnosed when culture or both urease and histological
      tests were positive. Serum pepsinogen-I (P-I) and pepsinogen-II (P-II) levels
      were measured. Atrophic gastritis was defined when P-I < or = 70 microg/L and P
      I/P-II < or = 3. A quantitative ELISA test (HEL-pTEST II) was used for IgG
      antibodies against H. pylori. RESULTS: The H. pylori prevalence rate was 62.1%.
      The sensitivity, specificity, positive predictive value, negative predictive
      value, and accuracy of ELISA were 93.5%, 94.4%, 95.6%, 91.9%, and 93.9% in
      patients aged < 45 years, and 100%, 81.3%, 94.3%, 100%, and 95.6% in patients
      aged > or = 45 years, respectively. Twenty-six patients had atrophic gastritis.
      There was 100% sensitivity and 86.7% specificity in atrophic gastritis and 96.5%
      sensitivity and 91.9% specificity in non-atrophic gastritis. CONCLUSION: The
      quantitative ELISA test is a good noninvasive test even in older age groups and
      is a suitable test in patients with atrophic gastritis due to its excellent
      sensitivity.

PMID- 20688301
TI  - Emergency peripartum hysterectomy: 16-year experience of a medical hospital.
AB  - BACKGROUND: We conducted this retrospective study to evaluate the outcomes and
      indications of emergency peripartum hysterectomy (EPH) as a life-saving
      procedure. METHODS: We analyzed a series of 140 cases of EPH, between January
      1993 and December 2008 in our clinic, retrospectively. The data were collected
      from the patients' files. The incidence, demographic characteristics, risk
      factors, indications and outcomes of hysterectomy, peripartum complications, the
      operation types, maternal morbidity and mortality and fetal mortality were
      evaluated. RESULTS: A total of 26,015 of women were delivered. The incidence of
      EPH was 5.38 per 1,000 deliveries. The mean age was 34.19 +/- 6.04 years (range,
      21-49 years), gravidity was 6.84 +/- 3.38 (1-17) and parity was 5.58 +/- 3.04 (0
      15). Of the 140 cases, 90 were delivered by cesarean section [29 (20.71%) of
      these had had a previous cesarean section] and 50 were vaginally delivered. One
      hundred and five cases had subtotal hysterectomy and 35 had total abdominal
      hysterectomy. The most common indications for EPH were uterine atony followed by
      uterine rupture and abnormal placentation. Mean operation time was 142.23 +/-
      43.70 minutes. The average blood transfusion was 4.79 +/- 3.36 (1-14) units.
      Relaparotomy was performed in 23 cases. Maternal mortality was seen in 13 cases.
      Seventy-nine of the cases delivered at an outside center and were referred to our
      clinic for the intensive care unit. Sixty-one of the cases delivered at our
      clinic and 31 had stillbirths. CONCLUSION: This study suggests that the most
      common indications for EPH are uterine atony, uterine rupture and abnormal
      placentation. This is probably due to the advanced age of pregnancies and
      multiparity in our region. Therefore, we believe that the risk of EPH may be
      decreased with appropriate and closer prenatal care as well as education of the
      pregnant women.

PMID- 20688302
TI  - Laparoscopic partial nephrectomy: Taipei veterans general hospital experience.
AB  - BACKGROUND: Laparoscopic partial nephrectomy (LPN) is a definitive therapy in
      patients with a small renal tumor. The aim of this study was to present our
      interim results of LPN with its complications and outcomes. METHODS: We conducted
      a retrospective chart review of 46 LPNs in 45 patients at Taipei Veterans General
      Hospital from April 2004 to September 2008. The perioperative data were
      prospectively collected. The follow-up data, including local recurrence, distant
      metastasis, and renal function, were recorded. RESULTS: The mean age of these 45
      patients was 54.8 years (range, 26-85 years). Three (6.5%) LPNs were converted to
      laparoscopic radical nephrectomy. The mean tumor diameter was 3.81 cm (range, 2.0
      7.5 cm). The mean operative time was 319 minutes (range, 180-660 minutes). The
      mean blood loss was 501 mL (range, 20-3,300 mL). Pedicle clamping was performed
      in 37 (80.4%) cases and the mean warm ischemic time was 56 minutes (range, 24-100
      minutes). There were 17 (40.0%) benign cases and 26 (56.5%) renal cell
      carcinomas, which were stage pT1a in 19 (73.1%) cases, pT1b in 5 (19.2%) cases,
      pT2 in 1 (3.8%) case, and pT3a in 1 (3.8%) case. The major complication rate was
      4.3% (delayed bleeding in 1 case and urine leakage in 1 case). All margins were
      free for the malignant cases. Neither distant metastasis nor mortality was found.
      Local recurrence was found in 1 patient. The mean preoperative creatinine was
      1.04 mg/dL (range, 0.6-2.4 mg/dL) and the mean elevated creatinine level was 0.10
      mg/dL at 3 months (p < 0.05) and 0.13 mg/dL at 6 months (p < 0.05)
      postoperatively. The function of the operated kidney was reduced by a mean of
      21.9% at 3 months (p < 0.05) and 27.7% at 6 months (p < 0.05) postoperatively.
      CONCLUSION: Although our warm ischemic time and operative time were longer than
      those of other LPN studies, the interim results of our oncologic and renal
      functional outcomes were encouraging. Further refinement of the procedure is
      needed to shorten the warm ischemic time and improve the hemostatic technique. In
      addition, based on postoperative renal function, LPN does not significantly
      influence long-term renal function.

PMID- 20688303
TI  - Increasing humidity blocks continuous positive airflow-induced apnea responses in
      rats.
AB  - BACKGROUND: The aim of this study was to investigate the role of temperature and
      humidity in positive continuous pressure flow-induced apnea. METHODS: Forty-two
      adult male Sprague-Dawley rats were used in a functionally isolated laryngeal
      animal model. In study 1, animals were challenged with laryngeal stimulation for
      1 minute to detect the possibility of adaptation. In study 2, different airflow
      conditions (25 degrees C dry-25 degrees C dry, 25 degrees C dry-25 degrees C wet,
      25 degrees C dry-37 degrees C dry and 25 degrees C dry-37 degrees C wet) were
      delivered to determine the role of temperature and humidity in the flow-induced
      apneic response of the larynx. The apneic index was calculated by prolonged
      expiratory time/baseline expiratory time. RESULTS: Laryngeal dry room temperature
      air exposure induced an apneic response, and this response was reproducible and
      could be eliminated by humidification. In contrast, this apneic response could
      not be inhibited by increasing temperature alone. In addition, prolonged cold dry
      air stimulation did not evoke a tachyphylactic effect to normalize the breathing
      pattern. CONCLUSION: Laryngeal cold dry air stimulation triggered an apneic
      response, which could be eliminated by humidification but not by the heating of
      air. These results suggest that using continuous positive airway pressure (CPAP)
      with humidified air decreases CPAP-induced apnea.

PMID- 20688304
TI  - Prescriptions of Chinese herbal medicine for constipation under the national
      health insurance in Taiwan.
AB  - BACKGROUND: Constipation is a common gastrointestinal problem worldwide. The aim
      of this study was to determine the frequency of use and prescriptive patterns of
      Chinese herbal medicine (CHM) in treating constipation by analyzing the claims
      data of traditional Chinese medicine (TCM) from the National Health Insurance
      (NHI) in Taiwan. METHODS: The computerized claims dataset of the TCM office
      visits and the corresponding prescription files in 2004 compiled by the NHI
      Research Institute in Taiwan were linked and processed. Visit files with the
      single diagnostic coding of constipation (ICD-9-CM code 564.0) were extracted to
      analyze the frequency and pattern of corresponding CHM prescriptions. The
      association rule was applied to analyze the co-prescription of CHM in treating
      constipation. RESULTS: There were 152,564 subjects who visited TCM clinics only
      for constipation in Taiwan during 2004 and received a total of 387,268 CHM
      prescriptions. Subjects between 20 and 29 years of age comprised the largest
      number of those treated (25.5%). Female subjects used CHM for constipation more
      frequently than male subjects (female:male = 3.31:1). There was an average of 4.6
      items of single Chinese herbs or formula in a single prescription for
      constipation. Ma-zi-renwan was the most commonly prescribed herbal formula, while
      Da-huang (Rheum palmatum) was the most commonly used single Chinese herb.
      According to the association rule, the most common prescribed pattern of 2-drug
      combination of CHM for treating constipation was Ban-xia-xie-xin-tang plus Ma-zi
      ren-wan, while the 3-drug combination of CHM was Fang-feng-tong-sheng-san, Rheum
      palmatum and Ma-zi-ren-wan. CONCLUSION: This study showed the pattern of single
      Chinese herbs or herbal formulae used in treating constipation in Taiwan. Further
      clinical trials are needed to evaluate the efficacy and safety of these CHMs in
      treating constipation.

PMID- 20688305
TI  - Scoliosis and syringomyelia with Chiari malformation after lumbar shunting.
AB  - Unsteady gait was noted in a 2-year-old boy with a lumboperitoneal (LP) shunt
      that had been inserted 1 year earlier for increased head circumference caused by
      communicating hydrocephalus. Scoliosis was also noted during postoperative follow
      up. Magnetic resonance imaging revealed new hindbrain tonsillar herniation and an
      extensive syrinx from C3 to L1. The malfunctioning LP shunt was removed and
      posterior fossa decompression with ventriculoperitoneal shunt insertion was
      performed. The unsteady gait recovered completely and scoliosis improved.
      Magnetic resonance imaging demonstrated resolution of the syrinx and tonsillar
      herniation. Acquired Chiari I malformation after LP shunt is well documented;
      usually, patients have no symptoms. This is the first report to have all the
      cause and effect mechanisms among syringomyelia, scoliosis and Chiari I
      malformation in 1 patient. We review the literature and discuss the possible
      mechanisms.

PMID- 20688306
TI  - Hepatic failure-induced hypogonadism in a prostate cancer patient.
AB  - Hypogonadism owing to systemic diseases in prostate cancer is rare. Here, we
      present a patient with metastatic prostate cancer to the pericardium who had low
      serum testosterone level due to hepatic failure. The patient had cardiac
      tamponade, and pericardiocentesis revealed sanguineous exudate. Cytology revealed
      adenocarcinoma. High serum prostate-specific antigen level of 244 ng/mL was
      detected. The patient experienced complications of stress gastric and duodenal
      ulcer perforation and underwent subtotal gastrectomy. Perioperative intra
      abdominal inflammatory process caused subsequent cholestasis and hepatic
      dysfunction. Transrectal ultrasound-guided prostate biopsy confirmed prostate
      cancer. Hypogonadism and a gradual decline in prostate-specific antigen were
      detected without any hormone therapy. The patient died due to hepatic failure in
      the 12(th) postoperative week.

PMID- 20688307
TI  - Sonographic and computed tomography findings of intra-abdominal desmoid tumor.
AB  - Intra-abdominal desmoid tumor is rare and seldom reported in the literature. It
      can grow large before causing symptoms, such as obstructing bowel loops or
      urinary system. Here, we present a 29-year-old male who suffered from intra
      abdominal desmoid tumor, and describe its imaging findings on ultrasound and
      abdominal computed tomography. This tumor usually presents as a large homogeneous
      hypodense solid mass on computed tomography, and demonstrates mild enhancement
      after contrast medium administration. Although rare, it should be included in the
      differential diagnosis when a patient presents with a large abdominal mass.

PMID- 20688308
TI  - Subtle solar retinopathy detected by fourier-domain optical coherence tomography.
AB  - Solar retinopathy is a retinal injury caused by direct or indirect sun-gazing and
      solar eclipse observation without protection. Subtle changes in the retinal
      damage might not be evident on fundus photography and fluorescein angiography. A
      40-year-old veteran suffered from paracentral scotoma in his left eye shortly
      after unprotected solar eclipse observation about 1 month earlier. His visual
      acuity was 6/5 in the right eye and 6/6 in the left. Anterior segments were
      normal bilaterally. Dilated fundus examination, fluorescein angiography, and
      central visual field testing did not reveal any abnormal findings. Fourier-domain
      optical coherence tomography was used for evaluation, and a focal defect in the
      inner and outer segments of the photoreceptor layer band was noted in the
      paracentral region of the fovea in the left eye, with central foveal thickness of
      198 microm. Solar retinopathy is preventable with adequate eye protection.
      Education should be reinforced to the public. In mildly affected individuals with
      subtle retinal damage, Fourier-domain optical coherence tomography could be a
      useful imaging tool to detect the disease.

PMID- 20688309
TI  - [Occipital sinus pericranii associated with giant cervical hemangioma].

PMID- 20688310
TI  - Role of electrostatic interactions during protein ultrafiltration.
AB  - A number of studies over the last decade have clearly demonstrated the importance
      of electrostatic interactions on the transport of charged proteins through
      semipermeable ultrafiltration membranes. This paper provides a review of recent
      developments in this field with a focus on the role of both protein and membrane
      charge on the rate of protein transport. Experimental results are analyzed using
      available theoretical models developed from the solution of the Poisson-Boltzmann
      equation for the partitioning of a charged particle into a charged pore. The
      potential of exploiting these electrostatic interactions for selective protein
      separations and for the development of ultrafiltration membranes with enhanced
      performance characteristics is also examined.

PMID- 20688311
TI  - Ophthalmomyiasis with a singular subretinal track.
AB  - PURPOSE: To report 3 cases of myiasis with a singular subretinal track in the
      Northeastern part of United States. DESIGN: Noninterventional case series.
      METHODS: Three patients from Pennsylvania were referred for evaluation of a
      linear and serpiginous retinal scar. Funduscopic examination and fluorescein
      angiography were performed to assess the referred retinal lesion. RESULTS:
      Funduscopic examination showed a singular subretinal track from the superior
      periphery to either the posterior pole or inferior midperiphery in the study
      cases. Fluorescein angiography showed exudative retinal detachment in all 3
      cases. Laser photocoagulation of the subretinal worm was performed in all
      reported cases. CONCLUSIONS: Our case series represents a report of singular
      subretinal tracks presumably caused by the warble fly larva in the Northeastern
      part of United States.

PMID- 20688312
TI  - Educational levels in patients with stargardt disease.
AB  - PURPOSE: To assess the highest educational level attained by patients with
      Stargardt disease and clinically significant visual impairment. DESIGN: Cross
      sectional assessment. METHODS: Patients with Stargardt disease and clinically
      significant visual impairment (documented best-corrected visual acuity of 20/70
      or worse in each eye either before or up to the age of 22 years) were included in
      the study. Information concerning the highest level of education attained was
      obtained for all participants by an interview. RESULTS: Of the 33 participants,
      32 completed high school. Either an associate's or bachelor's degree was attained
      by 21 patients (63.6%), whereas 3 patients (9.1%) were enrolled in college at the
      time of the interview. Further, a postgraduate degree (master's or doctorate) was
      attained by 7 patients (21.2%). CONCLUSIONS: Our findings document that the
      potential for attaining a higher degree of academic education beyond high school
      does not seem to be precluded by clinically significant visual impairment in
      Stargardt patients. This information can be useful for visual practitioners when
      counseling these patients and their families.

PMID- 20688313
TI  - Inflammatory disorders of the orbit in childhood: a case series.
AB  - PURPOSE: To describe a series of cases of orbital inflammatory disorders in
      children. DESIGN: Retrospective case series. METHODS: The medical records of
      pediatric patients diagnosed with orbital inflammation between September 1, 2002,
      and December 31, 2008, at Texas Children's Hospital were reviewed. Data collected
      included age at presentation, final diagnosis, treatment, workup and evaluation,
      need for biopsy and biopsy results, and involvement of lacrimal gland and
      muscles. RESULTS: Twelve cases were identified. Six cases were males and 6 were
      females with age at presentation ranging from 1.3 to 16.2 years (mean, 11.9
      years). The most common presentation was lacrimal gland enlargement, which was
      bilateral in 3 cases. Other common presenting signs were proptosis, extraocular
      motility limitation, and pain on eye movement. Half of our patients had systemic
      complaints at presentation, the most common of which was fever. Four patients
      were diagnosed as having a systemic cause and 2 of these patients had systemic
      symptoms. CONCLUSIONS: Idiopathic orbital inflammatory conditions in children are
      uncommon, but can be associated with systemic conditions. Patients typically have
      lacrimal gland involvement, pain with eye movement, proptosis, and motility
      deficits at presentation. Bilateral cases may have a higher incidence of systemic
      disease.

PMID- 20688314
TI  - Comparison of Travoprost and Bimatoprost plus timolol fixed combinations in open
      angle glaucoma patients previously treated with latanoprost plus timolol fixed
      combination.
AB  - PURPOSE: To compare the ocular hypotensive effect of bimatoprost plus timolol and
      travoprost plus timolol fixed combinations in glaucoma patients whose disease was
      controlled but had not reached their target intraocular pressure (IOP) with the
      fixed combination of latanoprost plus timolol. DESIGN: A 2 * 3-month,
      multicenter, prospective, randomized, double-masked, cross-over clinical trial.
      METHODS: Eighty-nine open-angle glaucoma (OAG) patients were included. After a 6
      week run-in period with latanoprost plus timolol, patients were randomized to
      either travoprost plus timolol or bimatoprost plus timolol for 3 months. Patients
      then switched to the opposite therapy for 3 additional months. The primary end
      point was the comparison of mean daily IOP after 3 months of each treatment.
      RESULTS: At baseline, mean IOP was 16.5 mm Hg (95% confidence interval, 16.0 to
      17.0 mm Hg) with treatment with latanoprost plus timolol. Both bimatoprost plus
      timolol and travoprost plus timolol statistically significantly reduced the mean
      IOP from baseline (P < .0001). Mean IOP at month 3 was statistically
      significantly lower in the bimatoprost plus timolol group compared with the
      travoprost plus timolol group (14.7 mm Hg [95% confidence interval, 14.3 to 15.3
      mm Hg] vs 15.4 mm Hg [95% confidence interval, 15.0 to 15.9 mm Hg]; P = .0041).
      IOP was lower during bimatoprost plus timolol treatment at all time points and
      statistical significance was reached at 8 am, 11 am, and 5 pm, but not at 2 pm
      and 8 pm. Both treatments showed similar tolerability profile. CONCLUSIONS:
      Bimatoprost plus timolol and travoprost plus timolol can provide additional IOP
      lowering effect in patients not fully controlled with latanoprost plus timolol.
      The observed additional IOP reduction was greater with bimatoprost plus timolol
      with a similar tolerability profile.

PMID- 20688315
TI  - Long-term changes in axial length in adult eyes with pathologic myopia.
AB  - OBJECTIVE: To examine the long-term changes of the axial length in adults with
      high myopia. DESIGN: Open-label, consecutive, retrospective case series. METHODS:
      The medical records of 101 patients (184 eyes) with high myopia (myopia >=-6
      diopters or axial length >=26.5 mm) were studied. The axial length of the eye was
      measured by A-scan ultrasonography. The significance of the changes in the axial
      length during follow-up was determined. The effects of the age, axial length, and
      the presence of a posterior staphyloma at the initial examination on the axial
      length elongation were determined. RESULTS: The mean follow-up period was 8.2
      years. The median axial length increased significantly from 28.6 mm at the
      initial examination to 29.4 mm at the final examination in the 184 eyes. The
      axial length remained stable (<=1-mm difference) in 69%, whereas the axial length
      increased by more than 1 mm in 31% of the eyes. For these 31%, the median axial
      length increased by 1.55 mm. An increase of the axial length per year was
      significantly greater in older patients than their younger cohorts, and the
      increase in eyes with a posterior staphyloma was significantly greater than in
      eyes without a staphyloma. Multiple regression analyses showed that the axial
      length elongation was positively and significantly correlated with patient age at
      the initial examination. CONCLUSIONS: In highly myopic adult patients, the axial
      length continued to increase. Older individuals with posterior staphyloma were
      more susceptible to having a larger increase in the axial length. A progression
      of posterior staphyloma with increasing age is considered a key factor for the
      continuous increase of axial length in adults with high myopia.

PMID- 20688316
TI  - Ischemic diabetic retinopathy may protect against nuclear sclerotic cataract.
AB  - PURPOSE: To determine whether diabetes mellitus is protective for nuclear
      sclerotic cataract at baseline and 6 and 12 months after vitrectomy surgery.
      DESIGN: Prospective, interventional cohort study. METHODS: Phakic diabetic and
      nondiabetic patients undergoing vitrectomy surgery for a variety of retinal
      conditions underwent Scheimpflug lens photography in the operated and fellow eye
      at baseline and at 6 and 12 months after vitrectomy surgery. RESULTS: Of 52 eyes
      included in the analysis, 23 eyes were from diabetic patients, 14 of which had
      surgery for ischemic retinopathy. At baseline, eyes with ischemic diabetic
      retinopathy had less nuclear sclerotic cataract than nonischemic diabetic and
      nondiabetic eyes. This was true for eyes undergoing vitrectomy surgery (P =
      .0001) and for fellow eyes (P = .003). Nuclear sclerotic cataract developed after
      vitrectomy surgery in nonischemic diabetic eyes and nondiabetic eyes at the same
      rate. Diabetic eyes with ischemic retinopathy showed no significant progression
      of nuclear opacification, and therefore had significantly less postvitrectomy
      nuclear cataract at 6 months (P < 1 * 10(-6)) and at 12 months (P < .001) than
      nondiabetic or nonischemic diabetic eyes. Normalizing to baseline opacity and
      adjusting for age and other comorbidities did not alter this result. CONCLUSIONS:
      Ischemic diabetic retinopathy, not just systemic diabetes mellitus, protected
      against nuclear sclerotic cataract at baseline and after vitrectomy surgery.
      These findings are consistent with the hypothesis that increased exposure to
      oxygen is responsible for nuclear cataract formation.

PMID- 20688317
TI  - Host and graft thickness after Descemet stripping endothelial keratoplasty for
      Fuchs endothelial dystrophy.
AB  - PURPOSE: To determine relationships between vision, forward scatter, and total
      corneal and graft thicknesses after Descemet stripping endothelial keratoplasty
      (DSEK). DESIGN: Prospective, cohort study. METHODS: Forty-four eyes with Fuchs
      endothelial dystrophy were examined before and at 1, 3, 6, and 12 months after
      DSEK; all eyes were pseudophakic after surgery. Central total corneal and graft
      thicknesses were measured using confocal microscopy. Best-corrected high-contrast
      visual acuity (BCVA) was measured using the electronic Early Treatment Diabetic
      Retinopathy Study protocol, and forward light scatter was measured using a
      straylight meter. RESULTS: Total corneal thickness was 610 +/- 50 MUm (mean +/-
      standard deviation) before DSEK, increased to 680 +/- 74 MUm by 1 month after
      DSEK (P < .001), and stabilized at 660 +/- 68 MUm by 3 months after DSEK (P = .03
      vs 1 month). Graft thickness was 170 +/- 57 MUm at 1 month, decreased to 157 +/-
      49 MUm by 3 months (P = .004), and then remained stable through 12 months (156 +/
      51 MUm; P = .99 vs 3 months). BCVA was 0.44 +/- 0.21 logarithm of the minimal
      angle of resolution (logMAR) units (Snellen equivalent, 20/55) before DSEK,
      improved to 0.26 +/- 0.20 logMAR units (Snellen equivalent, 20/36) by 3 months (P
      < .001), and improved to 0.16 +/- 0.16 logMAR units (Snellen equivalent, 20/29)
      at 12 months (P < .001 vs 3 months). BCVA and forward light scatter did not
      correlate with corneal or graft thickness after DSEK. CONCLUSIONS: Stromal edema
      resolves by 3 months after DSEK for Fuchs dystrophy, whereas visual acuity
      continues to improve through 12 months. Thicker corneas and grafts are not
      associated with worse visual acuity or increased forward scatter.

PMID- 20688318
TI  - Evaluation of the multivariate accommodation performance of the grid method.
AB  - The present study examined the multivariate accommodation performance (MAP) of
      the grid method, a distributed representative human models (RHM) generation
      method, in the context of men's pants sizing system design. Using the 1988 US
      Army male anthropometric data and +/- 2.5 cm of fitting tolerance, the grid
      method selected two key dimensions (waist girth and crotch height) out of 12
      anthropometric dimensions and identified 25 RHMs to accommodate 95% of the
      population. The average MAP of the RHMs decreased dramatically as the number of
      anthropometric dimensions considered increased (99% for single dimension and 14%
      for 12 dimensions). A standardized regression model was established which
      explains the effects of two factors (sum of anthropometric dimension ranges;
      adjusted R(2) between key dimensions and other anthropometric dimensions) on the
      MAP of RHMs. This regression model can be used to prioritize anthropometric
      dimensions for efficient MAP improvement of men's pants design.

PMID- 20688319
TI  - Evaluating the cognitive avoidance model of generalised anxiety disorder: impact
      of worry on threat appraisal, perceived control and anxious arousal.
AB  - Generalised anxiety disorder (GAD) is characterised by persistent and
      uncontrollable worry. According to the cognitive avoidance theory of GAD, worry
      may function as an affective dampening strategy motivated by intolerance of
      negative emotional states. By facilitating avoidance of more distressing
      cognitions and associated affect, worry is said to preclude modification of the
      fear representation in memory, maintaining threat associations and perpetuating
      further anxiety and worry. The present study evaluated these assumptions in a
      treatment-seeking GAD sample. Sixty-one participants were randomly allocated to
      conditions in which they were instructed to worry, imaginally process or relax in
      response to an anxiety trigger. Results supported the detrimental impact of
      worry, showing maintained threat expectancies and decreased control perceptions
      compared to other modes of processing. However, skin conductance level increased
      as a function of worry and there was no suggestion that worry suppressed
      affective responding. These findings highlight the need for clarification of the
      mechanisms involved in the maintenance of threat associations and worry in GAD.

PMID- 20688320
TI  - Regioselective facile one-pot Friedlander synthesis of sugar-based heterocyclic
      biomolecules.
AB  - Regioselective facile one-pot synthesis of 16 different sugar-based quinoline,
      naphthyridine, and xanthone derivatives is reported. The compounds are
      characterized by NMR spectroscopy and elemental analysis. The beta-Anomeric form
      of the sugar moiety was identified from (1)H NMR studies. Antimicrobial studies
      of these sugar-heterocyclic derivatives, 3a, 3b, 3f, 5c, 7a, 7b, and 7c show
      excellent activity against different microbes.

PMID- 20688322
TI  - Spelling impairments in Italian dyslexic children: phenomenological changes in
      primary school.
AB  - INTRODUCTION: Although spelling difficulties are constantly associated with
      developmental dyslexia, they have been largely neglected by the majority of
      studies in this area. This study analyzes spelling impairments in developmental
      dyslexia across school grades in Italian, a language with high grapheme-to
      phoneme correspondence. METHODS: The performances of 33 Italian dyslexic children
      attending Grades 3 and 5 were compared with those of age-matched control
      participants. Writing abilities were investigated through a spelling test that
      included regular words with one-sound-to-one-letter correspondence, regular words
      requiring the application of context-sensitive conversion rules, words with
      unpredictable transcription and nonwords with one-sound-to-one-letter
      correspondence. RESULTS: Both accuracy and error analyses indicate that the
      spelling impairment assumes different characteristics at different grades: Grade
      3 children showed an undifferentiated spelling deficit (involving regular words,
      regular nonwords and words with unpredictable spelling), whereas the fifth
      graders were prevalently impaired in writing words with unpredictable
      transcription. The error analysis confirms these results, with third graders
      producing a high rate of all types of errors (i.e., phonologically plausible,
      simple and context-sensitive conversion errors), whereas most errors committed by
      fifth graders were phonologically plausible. CONCLUSIONS: Results are coherent
      with the hypothesis that dyslexic children learning a shallow orthography suffer
      from delayed acquisition and some fragility of the sub-word level routine,
      together with a severe and long-lasting deficit of orthographic lexical
      acquisition.

PMID- 20688323
TI  - [Ecstasy: A disturbing old success].

PMID- 20688325
TI  - Luteal phase oocyte retrieval and in vitro maturation is an optional procedure
      for urgent fertility preservation.
AB  - OBJECTIVE: To compare the results of in vitro maturation (IVM) of oocytes for
      fertility preservation performed during the luteal phase of the cycle with those
      of IVM performed during the follicular phase. DESIGN: Retrospective chart review
      (August 2007 to June 2009). SETTING: Academic tertiary referral fertility center.
      PATIENT(S): Cancer patients who underwent treatment for fertility preservation.
      INTERVENTION(S): IVM treatment during either luteal or follicular phase. MAIN
      OUTCOME MEASURE(S): Number of oocytes, maturation and fertilization rates, and
      number of oocytes and embryos that were frozen. RESULT(S): Eighteen cancer
      patients underwent IVM fertility preservation, five in their luteal phase and 13
      in their follicular phase. The baseline characteristics of both groups were
      similar. There were no significant differences in the number of retrieved
      oocytes, maturation rates, fertilization rates, or the total number of oocytes
      and embryos that were cryopreserved. CONCLUSION(S): These results suggest that
      IVM during the luteal phase can be offered to patients as an optional treatment
      for urgent fertility preservation when there is insufficient time for
      conventional follicular phase oocyte retrieval before chemotherapy must be
      initiated.

PMID- 20688324
TI  - Stress reduces conception probabilities across the fertile window: evidence in
      support of relaxation.
AB  - OBJECTIVE: To assess salivary stress biomarkers (cortisol and alpha-amylase) and
      female fecundity. DESIGN: Prospective cohort design. SETTING: United Kingdom.
      PATIENT(S): 274 women aged 18 to 40 years who were attempting pregnancy.
      INTERVENTION(S): Observation for six cycles or until pregnancy: women collected
      basal saliva samples on day 6 of each cycle, and used fertility monitors to
      identify ovulation and pregnancy test kits for pregnancy detection. MAIN OUTCOME
      MEASURE(S): Salivary cortisol (MUg/dL) and alpha-amylase (U/mL) concentration
      measurements; fecundity measured by time-to-pregnancy and the probability of
      pregnancy during the fertile window as estimated from discrete-time survival and
      Bayesian modeling techniques, respectively. RESULT(S): Alpha-amylase but not
      cortisol concentrations were negatively associated with fecundity in the first
      cycle (fecundity odds ratio=0.85; 95% confidence interval 0.67, 1.09) after
      adjusting for the couples' ages, intercourse frequency, and alcohol consumption.
      Statistically significant reductions in the probability of conception across the
      fertile window during the first cycle attempting pregnancy were observed for
      women whose salivary concentrations of alpha-amylase were in the upper quartiles
      in comparison with women in the lower quartiles (highest posterior density: 
      0.284; 95% interval -0.540, -0.029). CONCLUSION(S): Stress significantly reduced
      the probability of conception each day during the fertile window, possibly
      exerting its effect through the sympathetic medullar pathway.

PMID- 20688326
TI  - Influence of embryo sex on development to the blastocyst stage and euploidy.
AB  - OBJECTIVE: To compare the prevalence of blastocyst development and euploidy in XX
      versus XY embryos. DESIGN: Retrospective cohort study. SETTING: Boston IVF, a
      large university-affiliated reproductive medicine practice. PATIENT(S): All
      patients who underwent their first preimplantation genetic screening cycle
      between January 1, 2006, and December 31, 2007. INTERVENTION(S): In vitro
      fertilization and preimplantation genetic screening. MAIN OUTCOME MEASURE(S):
      Proportion of embryos that developed to the blastocyst stage by day 5 and
      prevalence of euploidy for chromosomes 8, 13, 14, 15, 16, 17, 18, 20, 21, and 22
      in XX versus XY embryos. RESULT(S): Seven hundred fifty-eight embryos from 138
      cycles in 138 patients were analyzed. Three hundred sixty-six (48%) were XX, and
      392 (52%) were XY. XX and XY embryos were equally likely to develop to the
      blastocyst stage by day 5 and were equally likely to be euploid for the analyzed
      chromosomes. CONCLUSION(S): Our data suggest that extending embryo culture to day
      5 does not lead to sex selection and that euploidy and aneuploidy are not sex
      dependent.

PMID- 20688327
TI  - Insurance coverage and in vitro fertilization outcomes: a U.S. perspective.
AB  - OBJECTIVE: To compare the impact of mandated IVF insurance coverage on ET
      practices and resulting multiple pregnancy rates. DESIGN: Retrospective analysis
      of all fresh, nondonor IVF cycles performed in the United States in 2006.
      SETTING: United States. PATIENT(S): A total of 91,753 fresh, nondonor IVF cycles
      in the United States. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Pregnancy
      rate, live-birth rate, embryos transferred, multiple pregnancy rate. RESULT(S):
      Overall, nonmandated states had a significantly higher pregnancy rate (38.8% vs.
      35%) and live-birth rate (32.2% vs. 29.1%) than mandated states. Nonmandated
      states also had a significantly higher twin rate (28.1% vs. 26%) and triplet rate
      (3.9% vs. 3.4%). The average number of embryos transferred was also significantly
      higher in nonmandated states (2.6 vs. 2.2). These findings were more pronounced
      in the <35 and 35-37 age groups. CONCLUSION(S): In the last 8 years, despite a
      reduction in the average number of embryos transferred and multiple pregnancy
      rates, there is a continued association between mandated IVF coverage, the
      transfer of fewer embryos, and lower rates of multiple pregnancies and births,
      particularly in the younger age groups.

PMID- 20688328
TI  - Effect of the interval between onset of sustained fetal bradycardia and cesarean
      delivery on long-term neonatal neurologic prognosis.
AB  - OBJECTIVE: To examine the effect of the interval between onset of sustained fetal
      bradycardia and cesarean delivery on long-term neonatal neurologic prognosis.
      METHOD: A retrospective observational case-series performed with patients who had
      sudden-onset and sustained (<100 beats per minute) fetal bradycardia during
      labor. Fetal heart rate was monitored closely until cesarean delivery. The effect
      of the interval between the onset of bradycardia and delivery on neonatal
      neurologic prognosis was examined. RESULTS: Among 2267 deliveries in 2002-2003 at
      Kitasato University Hospital, 19 pregnancies met the inclusion criteria. Episodes
      of fetal bradycardia were due to umbilical cord prolapse (n=5), placental
      abruption (n=4), uterine rupture (n=3), maternal respiratory failure (n=1), and
      other causes (n=6). Mean onset of fetal bradycardia to delivery interval (BDI)
      was 20.5+/-8.9 minutes. Mean decision-to-cesarean delivery interval was 11.4+/
      3.9 minutes. BDI was negatively correlated with umbilical arterial pH at
      delivery. There were 3 postnatal deaths. Neurologic assessment at the age of 2
      years revealed that 15 of 16 children were neurologically normal. When the BDI
      was less than 25 minutes, all term pregnancies led to normal neonatal neurologic
      development. CONCLUSION: In the event of sustained intrapartum fetal bradycardia,
      delivery by emergency cesarean within 25 minutes improved long-term neonatal
      neurologic outcome.

PMID- 20688329
TI  - The apolipoprotein A5 (APOA5) gene predisposes Caucasian children to elevated
      triglycerides and vitamin E (Four Provinces Study).
AB  - OBJECTIVE: Apolipoprotein A-V plays an important role in lipid metabolism
      regulation, particularly modulating triglyceride levels, as has been shown by
      many association studies in adults. The aim of this study was to analyse the
      effect of APOA5 on lipid profiles and fat-soluble vitamins (due to its strong
      relationship with triglyceride metabolism) in children. METHODS: We determined
      polymorphisms -1131T>C and S19W in the APOA5 gene in 964 6-8-year-old
      participants of the 4P study and analysed the influence of the APOA5 gene on
      plasma lipid levels (total cholesterol, LDL cholesterol, HDL cholesterol and
      triglycerides), apolipolipoproteins (apo A-I and apo B) and fat-soluble
      antioxidant vitamin (alpha-tocopherol, gamma-tocopherol, lycopene, alpha
      carotene, beta-carotene and retinol) levels. RESULTS: The allele frequencies of
      both polymorphisms were comparable to those described in adult Caucasian
      populations (0.08 and 0.07 for -1131T>C and S19W, respectively). Boys carrying
      the -1131C allele have a 12% increase in circulating triglyceride levels
      (p=0.016) and a 7% decrease in HDL phospholipid levels (p=0.016). Linked to its
      effect on triglycerides, boys with the -1131C allele also have a 5% increase in
      plasma alpha-tocopherol levels (p=0.032). This effect was not observed in female
      participants. Boys carrying the rare allele for the S19W polymorphism have a 4%
      increase in circulating cholesterol levels (p=0.045), whereas girls have a 9%
      increase in circulating triglyceride levels (p=0.029). Linked to its effect on
      triglycerides, female carriers of the rare allele for S19W also have a 6%
      increase in alpha-tocopherol levels (p=0.009). CONCLUSION: In children, the
      effect of APOA5 gene variants on triglyceride levels is related to gender, and
      because of the strong relationship between lipid metabolism and fat-soluble
      antioxidant vitamins, it also involves a significant elevation in alpha
      tocopherol concentrations.

PMID- 20688330
TI  - Sulforaphane inhibits endothelial lipase expression through NF-kappaB in
      endothelial cells.
AB  - OBJECTIVE: Endothelial lipase (EL) is a new member of triacylglycerol lipase
      family that has been shown to decrease high-density lipoprotein (HDL) cholesterol
      levels leading to increased risk of atherosclerosis. Its expression is increased
      during inflammation and by inflammatory cytokines. Sulforaphane (SFN) is a
      naturally occurring isothiocyanate present in cruciferous vegetables that has
      antioxidant and anti-inflammatory effects. Nuclear factor (NF)-kappaB is one of
      the molecular targets for SFN-mediated protective effects. Our aim was therefore
      to assess whether SFN could impact on EL expression via modulation of NF-kappaB
      pathway. METHODS AND RESULTS: Quantitative PCR and Western blot results
      demonstrated that SFN inhibited tumor necrosis factor (TNF)-alpha-mediated
      induction of EL in human umbilical vein endothelial cells (HUVEC). Lentiviral
      transduction of HUVEC with mutated form of IkappaB-alpha (IkappaBM) as well as
      silencing of NF-kappaB subunit p65 using RNA interference revealed that TNF-alpha
      mediated induction of EL is mediated through NF-kappaB pathway. In addition, a
      total of five NF-kappaB binding sites were found in LIPG gene, which encodes EL.
      SFN inhibited binding of NF-kappaB to these sites analyzed by chromatin
      immunoprecipitation (ChIP) and electrophoretic mobility shift assay (EMSA). SFN
      also inhibited TNF-alpha mediated phosphorylation of IkappaB kinase (IKK) 1/2 and
      IkappaB-alpha. CONCLUSIONS: Collectively, these results indicate that SFN
      inhibits EL expression via inhibition of NF-kappaB which may have a beneficial
      effect on HDL cholesterol levels.

PMID- 20688331
TI  - Characterization of racemization of chiral pesticides in organic solvents and
      water.
AB  - Eight chiral pesticides, which were selected to cover different pesticide species
      and origins of chirality, were investigated to explore their chiral stability in
      organic solvents and water. Profenophos, fenamiphos, quizalofop-ethyl,
      dichlorprop-methyl (DCPP-methyl) and acetochlor were showed stable under all test
      conditions. However, significant racemization was observed for malathion,
      phenthoate and fenpropathrin in methanol, ethanol and water, but not in n-hexane,
      isopropanol, acetone or methylene chloride. The kinetic parameters (rate constant
      k and half-life T(1/2)) of the abiotic racemization were calculated through a
      mathematical model of the first-order reaction. Furthermore, the extent of
      racemization varied among the solvents and was also affected by temperature
      dependence. The racemization of malathion, phenthoate and fenpropathrin in water
      was documented to be pH-dependent and took place more rapidly at pH 7.0 than at
      pH 5.8. The observed racemization was deduced to occur via a proton exchange
      process at the chiral center, and the relationship between the abiotic
      racemization and pesticide structure was further explored. Findings from this
      study are useful for better understanding enantioselectivity of chiral pesticides
      in environment and also for proper analysis, formulating or handling of
      enantiopure products.

PMID- 20688332
TI  - Comparison of high-performance liquid chromatography separation of red wine
      anthocyanins on a mixed-mode ion-exchange reversed-phase and on a reversed-phase
      column.
AB  - Anthocyanins, which confer the characteristic color to red wine, can be used as
      markers to classify wines according to the grape variety. It is a complex
      separation that requires very high chromatographic efficiency, especially in the
      case of aged red wines, due to the formation of pyranoanthocyanins. A coelution
      between these kinds of compounds can affect the R(ac/coum) ratio of aged wines,
      and might lead to false results when classifying the wine variety. In 2007, the
      use of a novel mixed-mode ion-exchange reversed-phase column was reported to
      separate anthocyanins extracted from grapes of Vitis labrusca with different
      selectivity than C-18 columns. In the present work, the separation of
      anthocyanins including pyranoanthocyanins in young and aged Cabernet Sauvignon
      wines and other varieties is evaluated. The most interesting contributions of
      this research are the different elution order and selectivity obtained for
      anthocyanins and pyranoanthocyanins (only formed in wine), compared with those
      observed in C-18 stationary phases. Also interesting is the separation of the
      polymeric fraction, which elutes as a clearly separated peak at the
      chromatogram's end. However, a comparison with a high efficiency C-18 column with
      the same dimensions and particle size demonstrated that the tested mixed-mode
      column shows broader peaks with a theoretical plate number below 8000, for
      malvidin-3-glucoside peak, while it can be up to 10 times higher for a high
      efficiency C-18 column, depending on the column manufacturer. Under the tested
      conditions, in mixed-mode phase, the analysis time is almost twice that of a C-18
      column with the same dimensions and particle size. A mixed-mode phase with
      increased efficiency should provide an interesting perspective for separation of
      anthocyanins in wine, due to its improved selectivity, combined with a useful
      role in a second-dimension separation in preparative anthocyanin chromatography.

PMID- 20688333
TI  - A new concept of hollow fiber liquid-liquid-liquid microextraction compatible
      with gas chromatography based on two immiscible organic solvents.
AB  - A new concept of liquid-liquid-liquid microextraction (LLLME) was introduced
      based on applying two immiscible organic solvents in lumen and wall pores of
      hollow fiber (HF). With this methodology, analytes of interest can be extracted
      from aqueous sample, into a thin layer of organic solvent (dodecane) sustained in
      the pores of a porous hollow fiber, and further into a muL volume of organic
      acceptor (acetonitrile or methanol) located inside the lumen of the hollow fiber.
      Some chlorophenols (CPs) were selected as model compounds for developing and
      evaluating of the method performance. The analysis was performed by gas
      chromatography-electron capture detection (GC-ECD) without derivatization. The
      factors affecting the HF-LLLME of target compounds were investigated and the
      optimal extraction conditions were established. Under the optimum conditions,
      preconcentration factors in a range of 208-895 were obtained. The performance of
      the proposed method was studied in terms of linear dynamic ranges (LDRs from 0.02
      to 100ngmL(-1)), linearity (R(2)> or =0.995), precision (RSD %< or =8.1) and
      limits of detection (LODs in the range of 0.006-0.2ngmL(-1)). In addition to
      preconcentration, HF-LLLME also served as a technique for sample clean-up.

PMID- 20688334
TI  - Preparative separation of six antimycin A components from antimycin fermentation
      broth by high-speed counter-current chromatography.
AB  - A method of using high-speed counter-current chromatography (HSCCC) was
      established for preparative isolation and purification of antimycin A components
      from antimycin fermentation broth. Six antimycin A components were successfully
      purified for the first time by HSCCC with a two-phase solvent system composed of
      n-hexane-ethyl acetate-methanol-water (5:2:4:1, by volume). Total of 20mg
      antimycin A(4)(a or b), 25mg antimycin A(3)(a or b), 21mg antimycin A(8)(a or b),
      34mg antimycin A(2)(a or b), 26mg antimycin A(1)(a or b) and 34mg antimycin
      A(1)(a or b) with the purities of 93.2, 98.6, 96.2, 94.1, 94.9 and 96.7%,
      respectively, determined by high-performance liquid chromatography (HPLC), were
      yielded from 200mg crude sample only in one HSCCC run.

PMID- 20688335
TI  - Phosphate removal by hydrothermally modified fumed silica and pulverized oyster
      shell.
AB  - A calcined and hydrothermally annealed material for phosphate removal was
      prepared in a hollow cylindrical shape from fumed silica generated by a
      ferroalloy factory, and pulverized oyster shell. Phosphorus removal from
      wastewater by this material calcined at a range of temperatures (700-900 degrees
      C) and hydrothermally annealed at temperatures from 130 to 180 degrees C, for 8
      16 h, was investigated and the most suitable physicochemical conditions were
      determined. XRD, SEM, EDS, and XRF techniques were used to characterize the
      microstructures and compositions of the materials produced, and UV-Vis
      spectrophotometry using the ammonium phosphomolybdate blue method was used to
      determine the phosphate concentration in the wastewater. The results indicate
      that calcium carbonate in oyster shell reacted with SiO(2) in fumed silica and
      formed hydrated calcium silicate after hydrothermal treatment, and the hydrated
      calcium silicate reacted with phosphate ions in wastewaters to form
      hydroxyapatite precipitate. The optimal conditions for material production were
      calcination at 800 degrees C, and hydrothermal annealing at 150 degrees C for 12
      h. Materials made under these conditions showed 74% or 92% phosphate removal
      after 2 or 4 h, respectively.

PMID- 20688336
TI  - A theoretical analysis of the surface tension profiles of strongly interacting
      polymer-surfactant systems.
AB  - Measurements of the surface tension of static polymer-surfactant mixtures as the
      concentrations of polymer and surfactant are varied produce interesting and
      surprising profiles. It is well known how the critical points in the surface
      tension profile of a weakly interacting system relate to the formation of
      complexes in the bulk. However the critical points in the profiles of strongly
      interacting systems are much less well understood, and an important open question
      is what conditions are required for the formation of a peak. Here, using a model
      for the surface tension developed in a previous article (Bell et al., Langmuir 23
      (2007) 6042), we apply asymptotic techniques to show explicitly how the structure
      of the surface tension profile and the critical concentrations depend on the
      relative stability of the underlying polymer-surfactant complexes. We derive the
      interesting result that none of the critical concentrations is at the critical
      aggregation concentration (CAC). We also identify a criterion for the appearance
      of a peak in the surface tension profile, expressed in terms of the physical and
      chemical parameters of the system.

PMID- 20688337
TI  - The role of intelligence and feedback in children's strategy competence.
AB  - A test-intervention-test study was conducted investigating the role of
      intelligence on four parameters of strategy competence in the context of a
      numerosity judgment task. Moreover, the effectiveness of two feedback types on
      these four parameters was tested. In the two test sessions, the choice/no-choice
      method was used to assess the strategy repertoire, frequency, efficiency, and
      adaptivity of a group of low-, average-, and high-intelligence children. During
      the intervention, half of the participants from each intelligence group were
      given outcome feedback (OFB), whereas the other half received strategy feedback
      (SFB). The pretest data showed large differences among the three intelligence
      groups on all four strategy parameters. These differences had disappeared at the
      posttest due to a particularly strong improvement on all strategy parameters in
      the low-intelligence group. Furthermore, it was found that SFB was more
      beneficial than OFB for all parameters involving strategy selection. These
      results indicate that intelligence plays an important role in children's strategy
      use and suggest that strategy feedback can be a powerful instructional tool,
      especially for low-intelligence children.

PMID- 20688338
TI  - Predictors of parental quality of life after child open heart surgery: a 6-month
      prospective study.
AB  - OBJECTIVE: To prospectively assess parental health-related quality of life
      (HRQoL) and its predictors after child open heart surgery. STUDY DESIGN: Mothers
      (n = 135) and fathers (n = 97) of 138 children were assessed at discharge from
      hospital and 6 months after open heart surgery of their child. Parental HRQoL was
      compared with population norms. Medical, demographic, and psychosocial predictors
      of HRQoL were examined. RESULTS: In both parents, several domains of HRQoL were
      decreased at their child's hospital discharge with mothers showing lower HRQoL
      than fathers. Mental domains were more affected than physical domains. At 6
      months, parental HRQoL was within or above population norms. At discharge,
      symptoms of post-traumatic stress and at 6 months a high impact of the child's
      disease on family life were associated with low mental HRQoL in both parents. In
      mothers, lower socioeconomic status and foreign nationality were also associated
      with a higher risk for low mental HRQoL at discharge. CONCLUSIONS: Parents'
      mental HRQoL is low in the immediate period after their child's open heart
      surgery but normalizes after 6 months. However, parents in whom the child's
      disease has a high impact on their family life are at increased risk for
      persistent low mental HRQoL.

PMID- 20688340
TI  - Surfactant proteins and respiratory syncytial virus.

PMID- 20688341
TI  - Bias in self-reported height and weight in preadolescents.
AB  - OBJECTIVES: To examine the validity of self-reported height and weight and
      factors related to misreporting in preadolescents. The accuracy of screening for
      underweight (thinness), overweight, and obesity using self-reported data was also
      tested. STUDY DESIGN: Self-reported height and weight was administered and then
      measured in 798 fourth graders age 8 to 11 years. Body mass index (BMI) was
      calculated from self-reported and measured data and BMI categories were
      determined using international age- and sex-specific BMI criteria. RESULTS:
      Preadolescents overestimated their height by 0.54 +/- 5.17 cm and underreported
      their weight by 0.80 +/- 3.09 kg. BMI derived from self-reported data was
      underestimated by 0.47 +/- 1.79 kg/m2. Measured BMI category was an important
      independent predictor of bias in self-reported weight and BMI. Children who were
      overweight or obese underestimated their weight and BMI to a greater degree
      compared with normal weight/underweight children. The influence of
      sociodemographic factors on bias in self-reported values was relatively small.
      Approximately 15% of children were misclassified in BMI categories when self
      reported data were used, especially in the underweight (thinness) and obese
      category. CONCLUSIONS: Children age 8 to 11 years were not able to accurately
      estimate their actual height and weight, leading to erroneous estimating rates of
      their weight status.

PMID- 20688343
TI  - Intra-arterial thrombolytic therapy for acute intracranial large artery occlusive
      disease in patients selected by magnetic resonance image.
AB  - BACKGROUND AND PURPOSE: We reported an experience of intra-arterial thrombolysis
      (IAT) study triaged by emergent MRI. METHODS: Patients were recruited if vascular
      occlusions were identified by emergent MRA. Urokinase was infused
      hyperselectively within 6h after onset to a maximum dose of 900,000IU or
      recanalization achieved with mechanical thrombus disruption. Heparin infusion was
      discontinued after 2 hemorrhage in the first 7 patients. TIMI grade 2 and 3
      recanalization was recognized as successful. Favorable outcomes were mRS 0-3 at
      3months. RESULTS: Among 4225 ischemic stroke patients during the 29months study
      period, 52 patients met the inclusion criteria with 49 screened by MRA and 3
      screened by CT, 30 patients were enrolled and 25 were treated. Three patients
      (10%) were unable for the MRI examination due to time or equipment limit. There
      were 5 ICA, 13 MCA, and 7 VBA occlusions. Among 27 patients screened from MRA, 25
      patients had the same occluded vessels and 2 patients had compatible occluded
      vessels confirmed by cerebral angiography. The median NIHSS was 26 and median
      time from symptom onset to IAT was 283min. Successful recanalization was achieved
      in 68% (17/25). Intracerebral hemorrhage was recognized as symptomatic in 3 (12%)
      and asymptomatic in 8 (32%) at 3months. Mortality was 32%. 36% patients had a mRS
      of 0-3 at 3months. Patients with lower initial NIHSS score (20.9 vs. 28.4,
      P=0.02) and MCA occlusions (69.3%, 9/13, P<0.001) tend to have favorable
      outcomes. CONCLUSIONS: Though the incidence was low, IAT triage with emergent MRI
      appeared to be feasible. MRI screening might be incorporated in the future IAT
      studies. Mechanical thrombus disruption and heparin infusion in IAT might need
      further investigation in this area.

PMID- 20688344
TI  - Inherent optical properties and satellite retrieval of chlorophyll concentration
      in the lagoon and open ocean waters of New Caledonia.
AB  - The retrieval of chlorophyll-a concentration from remote sensing reflectance
      (Rrs) data was tested with the NASA OC4v4 algorithm on the inner New Caledonian
      lagoon (Case 2) and adjacent open ocean (Case 1) waters. The input to OC4v4 was
      Rrs measured in situ or modeled from water's inherent optical properties (2001
      2007). At open ocean stations, backscattering and absorption coefficients were
      correlated with chlorophyll (R(2)=0.31-0.51, respectively), in agreement with
      models for Case 1 waters. Taking spectrofluorometric measurement as reference,
      the OC4v4 model leads to an average underestimation of 33% of the chlorophyll
      concentration. For the lagoon waters, OC4v4 performed inadequately because the
      backscattering coefficient, highly correlated with turbidity and suspended matter
      (R(2)=0.98), was poorly correlated to chlorophyll (R(2)=0.42). The OC4v4
      performance was better in deep lagoon waters for stations with a TDT index (Tchla
      x depth/turbidity) higher than 19 mg m(-2) NTU(-1) (R(2)=0.974, bias=10.2%).
      Global Imager Rrs provided a good estimate of Tchla (R(2)=0.79, N=28) in the
      deeper part of the lagoon.

PMID- 20688345
TI  - [Plexiform neurofibroma of the ileum and mesentery: an uncommon manifestation of
      neurofibromatosis type I].
AB  - Plexiform neurofibroma is a tumor of the nerve trunks and their branches; it is
      considered virtually pathognomic of neurofibromatosis type 1. We present the case
      of a patient with neurofibromatosis type 1 and a plexiform neurofibroma involving
      the ileum and mesentery. This case is interesting because intestinal involvement
      by neurofibroma is rare and because the patient presented with symptomatic
      intestinal involvement that required surgery.

PMID- 20688346
TI  - [Radiological approach to cardiac tamponade].
AB  - Cardiac tamponade is a life-threatening medical emergency. The radiologist's role
      in the clinical management of patients with cardiac tamponade is usually minor
      and nearly always limited to the diagnostic process, and the condition is
      normally treated by other specialists. In this review, we aim to provide readers
      with the essential information to enable a complete diagnostic and therapeutic
      radiological approach. We emphasize US-guided percutaneous pericardial drainage;
      when performed correctly, this technique improves patients' symptoms immediately
      with minimal discomfort and a very low rate of complications.

PMID- 20688347
TI  - [Criminal court expert reports].
AB  - In relation with the structured pattern of crime today, and owing to the
      evolution observed among sciences and techniques, the legal system more and more
      frequently requires expert advice in numerous criminal cases with increasing
      technicality. The expert and the investigating officer appear to be of equal
      importance regarding the advices on which the judge bases both his evidence
      appreciation and his judgement when giving a ruling on a suspect's potential
      culpability.

PMID- 20688348
TI  - How to live at very low substrate concentration.
AB  - Availability of carbon/energy sources and temperature are the two environmental
      factors that severely restrict heterotrophic growth in most ecosystems. DOC
      concentrations in ground, drinking and surface waters are typically in the range
      of 0.5-5 mg/L, but most of this is present in a polymeric, inaccessible form for
      microbes. Concentrations of microbiologically available carbon compounds (so
      called assimilable organic carbon, AOC) are usually in the range of 10-100 MUg/L,
      those of individual sugars or amino acids are not higher than a few MUg/L. Until
      recently microbiologists assumed that such nutrient-poor (oligotrophic)
      environments are "deserts" for life, and that the majority of bacterial cells
      seen in the microscope are dead, dormant or at least severely starved.
      Nevertheless, despite the low concentrations of available carbon compounds,
      bacterial cell numbers recorded in these environments typically are in the range
      of 10(5)-10(6) per mL. Over the last years, we have learnt that most of these
      microbes are perfectly alive, metabolizing and ready to grow when given the
      chance. Hence, microbes have adapted and developed strategies to cope with this
      situation. Laboratory studies with pure cultures suggest that bacterial cells
      have developed two strategies to live under such conditions. The first strategy
      is to perform a "multivorous" way of life by taking up and metabolizing dozens of
      different carbon substrates simultaneously (i.e., they are NOT specializing on a
      particular substrate, which they can take up with very high affinity). This
      "mixed substrate growth" equips the cell with a kinetic advantage and metabolic
      flexibility. Simultaneous utilization of a multitude of carbon substrates allows
      fast growth at minute concentrations of individual substrates. The second
      strategy is to minimize maintenance requirements (unfortunately we still know
      little about how this is achieved). Recently, flow cytometry has been employed to
      study microbial growth in very dilute, nutrient-poor environments. The technique
      allows fast and easy quantification of microbial growth of natural bacterial
      communities, including "uncultivable" members, under environmental conditions.
      When combined with strain-specific fluorescent immunoprobes, this technique
      allows investigation of the growth and competition of pathogens with the
      indigenous microbial flora. This method is particularly suited for studying
      questions concerning microbial growth and survival in drinking water systems.

PMID- 20688349
TI  - Cytogenetic and developmental toxicity of cerium and lanthanum to sea urchin
      embryos.
AB  - The aim of this study was to evaluate the toxicity of two rare earth elements
      (REE), cerium and lanthanum on sea urchin embryos and sperm. Sea urchin
      (Paracentrotus lividus) embryos were reared for 72 h in Ce(IV)- or La(III)
      contaminated seawater at concentrations ranging from 10(-8) to 10(-5) M. Cleaving
      embryos (5h post-fertilization) were submitted to cytogenetic analysis, scoring
      mitotic activity and a set of mitotic aberrations. Embryological analysis was
      carried out to determine percent developmental anomalies and/or embryonic
      mortality. P. lividus sperm were suspended in Ce(IV) or La(III) (10(-8)-10(-5)M)
      for 1h, and percent fertilized eggs were scored in cleaving embryos that were
      cultured up to pluteus stage to score any developmental defects. Embryos reared
      in 10(-5)M Ce(IV) resulted in 100% embryonic mortality, whereas 10(-5)M La(III)
      induced 100% developmental defects, without causing any embryonic mortality. A
      significant concentration-related mitotoxic effect and induction of mitotic
      aberrations were observed in Ce(IV)-exposed, but not in La(III)-exposed embryos,
      at concentrations ranging from 10(-7)M to 3 x 10(-6)M. Following sperm exposure,
      both Ce(IV) and La(III) induced a decrease in sperm fertilization success at the
      highest tested concentration (10(-5)M). The offspring of Ce(IV)-exposed, but not
      of La(III)-exposed sperm displayed a significant concentration-related increase
      in developmental defects. The results may suggest adverse impacts in REE-exposed
      biota and warrant further studies of a more extended REE series.

PMID- 20688350
TI  - Polysulfide as a novel chemical agent to solidify/stabilize lead in fly ash from
      municipal solid waste incineration.
AB  - Polysulfide was produced and tested for use as an inexpensive chemical agent for
      the solidification/stabilization of lead in fly ash, generating little hydrogen
      sulfide gas. According to the equations S(n)(2-)-->S+S(n-1)(2-) and S(n)(2-)+H(+)
      ->HS(-)+S(n-1), this agent was expected to achieve long-term stability of
      disposed Pb. The leachate concentration of Pb in fly ash after sulfide treatment
      showed a decrease-increase-decrease trend. We also compared Pb leaching behavior
      from an aging/weathering experiment to thermodynamic modeling using the database
      from the Geochemist's Workbench software. Thermodynamic modeling indicated the
      tendency that when the precipitate was formed in the order of PbO, PbCO(3).PbO,
      and PbCO(3), the total concentration of soluble Pb will be lowered. The leaching
      curve of Pb in fly ash without a lime slurry injection system was close to PbO,
      whose activity was initially near 1, but when leaching time increased, it shifted
      to that of PbCO(3).PbO, before finally ending at that of PbCO(3). However,
      Ca(OH)(2) sprayed on fly ash interfered with the carbonation process of Pb.

PMID- 20688351
TI  - Activation of the transcription factor c-Jun in acute cellular and antibody
      mediated rejection after kidney transplantation.
AB  - c-Jun is a transcription factor that belongs to the activator protein-1 family of
      proteins. In human kidney disease, c-Jun is activated in glomerular and tubular
      cells and plays a major role in renal pathophysiology. However, the contribution
      of this pathway to renal allograft rejection has not been determined. We
      investigated whether c-Jun is activated in acute allograft rejection. c-Jun
      activation was assessed with immunohistochemistry using phospho-specific c-Jun
      antibodies in control human renal tissue and renal tissue from patients with
      acute cellular rejection, acute antibody-mediated rejection, and no rejection in
      the month after transplantation. In patients with acute cellular rejection, c-Jun
      activation was observed primarily in infiltrated T cells associated with
      tubulitis, interstitial cell infiltration, and endarteritis. The number of
      infiltrated phosphorylated c-Jun-positive cells in the tubules and interstitium
      was correlated with the Banff classification "t" and "i" scores. In patients with
      acute antibody-mediated rejection, c-Jun activation was observed in injured
      endothelial cells as well as in infiltrated cells, including macrophages, in the
      glomerular and peritubular capillaries. Furthermore, the serum creatinine levels
      and changes in serum creatinine from the previous year were significantly
      correlated with the total tubulointerstitial phosphorylated c-Jun-positive score
      (representing the number of positive nuclei in the tubules, interstitium, and
      peritubular capillaries). In conclusion, c-Jun was activated in acute antibody
      mediated rejection and acute cellular rejection and was associated with reduced
      graft function. These findings suggest that c-Jun plays a key role in
      pathological events and may represent a novel therapeutic target in acute renal
      allograft rejection.

PMID- 20688352
TI  - Core needle biopsy in benign lung lesions: pathologic findings in 159 cases.
AB  - Although core needle biopsy has been shown to be an accurate means of diagnosing
      lung malignancies, there is relatively little information in the literature about
      its utility in diagnosing specific non-malignant conditions. We reviewed the
      pathologic findings in 159 core needle biopsies showing benign changes in order
      to determine the types of processes that can be diagnosed by this technique and
      the factors that influence accuracy and specificity. There were 155 patients
      ranging in age from 3 to 86 years (mean 58). Nodules or masses were present
      radiologically in most. They ranged from 0.5 to 8.0 cm (mean 1.65 cm) in size and
      80% measured 2.0 cm or less. Twenty percent were spiculated, and positron
      emission tomography scans were positive in 48 of 56 cases tested (30% of total).
      Specific diagnoses were established in 122 (77%) of 159 core needle biopsies,
      while 24 (15%) were nonspecific and 13 (8%) were nonrepresentative. The most
      common specific diagnoses were necrotizing granulomatous inflammation (45), scar
      (28), organizing pneumonia (13), and benign neoplasms (11). A mixture of
      interstitial fibrosis and chronic inflammation (16) was the most common
      nonspecific diagnosis. A specific diagnosis was significantly more likely in
      biopsies with 3 or more cores or with a core length of more than 1 cm. Malignancy
      was diagnosed on a subsequent biopsy in only one case, and the initial biopsy in
      that case showed non-specific chronic inflammation and fibrosis. Our findings
      confirm that core needle biopsy is an accurate method of diagnosing benign lung
      lesions, yielding specific diagnoses in the majority.

PMID- 20688353
TI  - Reduced expression of Raf-1 kinase inhibitory protein is a significant prognostic
      marker in patients with gallbladder carcinoma.
AB  - Gallbladder carcinoma is one of the most aggressive malignancies. It is usually
      diagnosed at an advanced stage, and the prognosis remains poor despite advances
      in imaging techniques and aggressive surgical treatment. Because of the lack of
      reliable prognostic markers, the aim of this study was to investigate the
      prognostic significance of Raf-1 kinase inhibitory protein expression in
      gallbladder carcinomas. Immunostaining for Raf-1 kinase inhibitory protein was
      performed on chronic cholecystitis, adenoma, carcinoma in situ, and primary and
      nodal metastatic gallbladder carcinoma. Raf-1 kinase inhibitory protein
      expression was reduced in 68.8% (11/16) and 42.3% (44/104) of nodal metastatic
      and primary gallbladder carcinoma cases, respectively, but in no case of
      carcinoma in situ, adenoma, or chronic cholecystitis. The differences in Raf-1
      kinase inhibitory protein expression in gallbladder carcinoma versus
      nongallbladder carcinoma tissues (P < .001), and in nodal metastatic gallbladder
      carcinoma versus primary gallbladder carcinoma (P = .009), were statistically
      significant. Kaplan-Meier curves showed that patients with Raf-1 kinase
      inhibitory protein-negative or weakly positive gallbladder carcinoma had a
      significantly shorter overall survival than did patients with Raf-1 kinase
      inhibitory protein-positive gallbladder carcinoma (median, 14 versus 120 months;
      P = .011). Multivariate survival analysis showed that reduced Raf-1 kinase
      inhibitory protein expression was an independent prognostic predictor for overall
      survival (P = .020). Our results suggest that reduction in Raf-1 kinase
      inhibitory protein expression in gallbladder carcinoma contributes to invasion
      and metastasis and is a significant prognostic marker in patients with
      gallbladder carcinoma.

PMID- 20688354
TI  - Differential expression of CKS-1B in typical and blastoid variants of mantle cell
      lymphoma.
AB  - Mantle cell lymphoma is a distinct type of B-cell lymphoma characterized by the
      t(11;14)(q13;q32). Mantle cell lymphomas exhibit a spectrum of morphologic
      findings, of which a subset of tumors is clinically aggressive with a high
      proliferation rate. These neoplasms are known as aggressive variants of which
      there are blastoid and pleomorphic subsets. CKS-1B (CDC28 protein kinase
      regulatory subunit 1B) is essential for the ubiquitination and degradation of p27
      and cell cycle progression. We analyzed CKS-1B expression in mantle cell lymphoma
      cell lines and tumors by Western blot and immunohistochemical analysis. In 4
      mantle cell lymphoma cell lines, CKS-1B was expressed at variable levels and
      correlated inversely with p27 expression. In mantle cell lymphoma tumors, CKS-1B
      was positive in 10 (28.6%) of 35 typical versus 14 (87.5%) of 16
      blastoid/pleomorphic cases (Fisher exact test, P = .0002). Analyzed as a
      continuous variable, the percentage of CKS-1B-positive cells significantly
      correlated with blastoid/pleomorphic morphology (Mann-Whitney U test, P = .001).
      Twelve (23.5%) of 51 mantle cell lymphoma tumors expressed p27. Proliferation
      rate (Ki-67) was higher in blastoid/pleomorphic variants than in typical mantle
      cell lymphoma tumors and was inversely associated with p27 levels in typical
      mantle cell lymphoma. However, CKS-1B expression did not correlate with p27
      expression, proliferation rate, or prognosis in the entire study group.
      Fluorescence in situ hybridization analysis of 10 CKS-1B-positive mantle cell
      lymphoma tumors showed no evidence of CKS-1B gene amplification. We conclude that
      CKS-1B is commonly expressed in mantle cell lymphoma, particularly in aggressive
      histologic variants, and may be involved in pathogenesis.

PMID- 20688355
TI  - Adenoid cystic carcinomas of the breast have low Topo IIalpha expression but
      frequently overexpress EGFR protein without EGFR gene amplification.
AB  - Adenoid cystic carcinoma of the breast is a rare subtype of breast cancer with
      basal-like features. Published studies on breast adenoid cystic carcinoma are
      limited, resulting in relatively scarce information on the value of predictive
      tumor markers. We studied 20 primary cases of adenoid cystic carcinoma of the
      breast for expression of estrogen receptor, progesterone receptor, androgen
      receptor, epidermal growth factor receptor, HER-2/neu, and topoisomerase IIalpha
      using immunohistochemistry and fluorescent in situ hybridization methods.
      Estrogen and progesterone receptor expression were detected in 1 case each. All
      tumors were uniformly negative for Her-2/neu expression. Androgen receptor and
      topoisomerase IIalpha expression were weakly positive in three cases and 7 cases,
      respectively. Epidermal growth factor receptor overexpression was detected in 13
      cases (65% of all cases). Amplification of TOP2A or HER-2/neu gene was not
      detected in any of the cases. Our study shows that the majority of adenoid cystic
      carcinomas of the breast do not overexpress Her-2/neu, topoisomerase IIalpha, or
      estrogen receptor, and thus, they are unlikely to respond to therapies targeting
      these proteins. However, these tumors frequently over-express epidermal growth
      factor receptor, indicating a potential benefit from anti-epidermal growth factor
      receptor therapy for patients with advanced adenoid cystic carcinomas of the
      breast.

PMID- 20688357
TI  - 'Putting flesh back onto the bones?' Can we predict soft tissue properties from
      skeletal and fossil remains?
AB  - Estimates of muscle and other soft tissue properties derived from hominin
      skeletal and fossil remains would greatly enhance descriptions of body size and
      shape, and prior physical and metabolic capabilities. Presently, the utility of
      this approach is uncertain given the complex nature of the relationship between
      muscle and bone. To address various principal issues, peripheral quantitative
      computed tomography (pQCT) imaging was used to quantify these relationships at
      the midshaft of the arm, forearm, and lower leg of modern human athletes
      (runners, field hockey players, swimmers, and cricketers) and control subjects.
      Given the presumed behavior patterns of prehistoric hominins, the inclusion of
      highly active human participants was required. Soft tissue and muscle area was
      compared with bone area, diaphyseal shape, and torsional rigidity. Relationships
      were found between muscle area and bone area in the arm, and muscle area and
      torsional rigidity in the forearm. However, the high standard error and
      prediction error that define these relationships indicate that muscle or other
      soft tissue predictions derived from hominin fossil or skeletal remains would be
      untenable. In the tibia, the relationship between soft tissue properties and bone
      properties were primarily explained by covariation with body size. While the
      strength of the muscle-bone relationships in the arm and forearm vary among
      athletes and control subgroups, it appears that habitual upper limb loading
      performed throughout adolescence neither strengthens nor weakens this
      relationship. Future attempts to estimate soft tissue properties from osseous
      tissue may be improved through the use of medical CT or MRI to image complete
      limb segments and isolate individual muscles.

PMID- 20688356
TI  - High-definition characterization of cerebral beta-amyloid angiopathy in
      Alzheimer's disease.
AB  - The occurrence and progression of cerebral beta-amyloid angiopathy and beta
      amyloid plaques in sporadic Alzheimer's disease may be attributed to aging
      related deficiencies in beta-amyloid drainage along cerebral perivascular
      pathways. To elucidate high-definition characteristics of cerebral beta-amyloid
      deposition, we performed immunogold silver staining for beta-amyloid-40 and beta
      amyloid-42 on semithin LR White-embedded tissue sections from 7 Alzheimer's
      disease/severe cerebral beta-amyloid angiopathy, 9 Alzheimer's disease/mild
      cerebral beta-amyloid angiopathy, 5 old control, and 4 young control autopsy
      brains. In vessel walls, beta-amyloid-40 and beta-amyloid-42 deposits were
      unevenly distributed along the adventitia and among the medial smooth muscle
      cells. beta-Amyloid-40 immunoreactivity appeared greater than that of beta
      amyloid-42 in vessel walls, with beta-amyloid-42 being preferentially located on
      their abluminal regions. In capillary walls, either beta-amyloid-40 or beta
      amyloid-42 deposits or both were present in 6 of 7 severe cerebral beta-amyloid
      angiopathy and in 1 of 9 mild cerebral beta-amyloid angiopathy cases, with a
      marked variation in thickness and focally abluminal excrescences. In 5 of 7
      severe cerebral beta-amyloid angiopathy cases, a subset of beta-amyloid-laden
      capillaries revealed either beta-amyloid-40 or beta-amyloid-42 deposits or both
      radiating from their walls into the surrounding neuropil ("pericapillary
      deposits"). No vascular beta-amyloid-40 or beta-amyloid-42 deposits were observed
      in any of the controls. In conclusion, the patterns of beta-amyloid-42 and beta
      amyloid-40 immunoreactivity in vessel walls suggest that beta-amyloid deposits
      occur in the vascular basement membranes along cerebral perivascular drainage
      pathways, extending from cortical capillaries to leptomeningeal arteries. The
      presence of pericapillary beta-amyloid deposits suggests that a subset of beta
      amyloid plaques originate from beta-amyloid-laden capillaries, particularly in
      Alzheimer's disease brains that exhibit preferential capillary involvement by
      cerebral beta-amyloid angiopathy.

PMID- 20688358
TI  - Subclinical entheseal involvement in patients with psoriasis: an ultrasound
      study.
AB  - OBJECTIVES: The main aim of the present study was to determine the prevalence of
      subclinical entheseal involvement at lower limbs by ultrasound (US) in patients
      with psoriasis. The secondary aim was to determine the interobserver reliability
      of the Glasgow Ultrasound Enthesitis Scoring System (GUESS) and power Doppler
      (PD) technique in the assessment of enthesopathy. METHODS: The study was
      conducted on 45 patients with psoriasis and 45 healthy sex- and age-matched
      controls. All patients with no clinical evidence of arthritis or enthesitis
      underwent an US examination. All US findings were identified according to GUESS.
      The interobserver reliability was calculated in 15 patients with psoriasis.
      RESULTS: A total of 450 entheses in 45 patients with psoriasis were evaluated by
      US. In 148 of 450 (32.9%) entheses, grayscale US found signs indicative of
      enthesopathy. In 4/450 (0.9%) entheses PD signal was detected. In the healthy
      population, US found signs of enthesopathy in 38 of 450 (8.4%) entheses and no PD
      signal was detected. The GUESS score was significantly higher in patients with
      psoriasis than in healthy controls (P < 0.0001). Both concordance correlation
      coefficient and unweighted kappa values for US findings showed an excellent
      agreement (0.906 and 0.890, respectively). CONCLUSIONS: Our results indicate that
      both grayscale US and PD findings indicative of enthesopathy were more frequent
      in patients with psoriasis. The US ability to detect signs of subclinical
      enthesopathy should be the object of longitudinal investigations to define its
      value in predicting the clinical onset of psoriatic arthritis.

PMID- 20688359
TI  - Venous thromboembolism risk assessment and thromboprophylaxis among hospitalized
      acute medical patients in China--the RAMP study.
AB  - BACKGROUND: In developed countries, hospitalized patients with acute medical
      conditions are at significant risk for venous thromboembolism (VTE). Little is
      known about VTE risk and prophylaxis practices in China. OBJECTIVE: To determine
      the VTE risk and the frequency of recommended VTE prophylaxis in hospitalized
      Chinese patients with acute medical conditions. METHODS: Multi-center, cross
      sectional, observational study. ELIGIBILITY CRITERIA: >=30 years, admitted to an
      intensive care unit (ICU)/coronary care unit (CCU) for acute medical illness, had
      >=1 VTE risk factor/1 disease that predisposes to VTE, and provided informed
      consent. We used 2004 American College of Chest Physicians (ACCP) evidence-based
      consensus guidelines to assess VTE risk and the frequency of recommended VTE
      prophylaxis. RESULTS: 1247 patients from 19 hospitals in 11 cities across 11
      provinces of China were enrolled from July 2007 to June 2008. 57.3% patients had
      >2 VTE risk factors. Only 20.2% received ACCP-recommended VTE prophylaxis (CCU
      patients: 22.7%, ICU patients: 16.9%, p=0.0117). LIMITATIONS: Excluding some
      patients with VTE risk factors did not allow assessment of the prevalence of VTE
      risk in the acute hospital-care setting. We could not determine whether the
      duration of prophylaxis complied with the ACCP recommendations. Our results may
      not be representative of hospitals in small cities/rural areas in China.
      CONCLUSIONS: The prevalence of VTE risk factors in Chinese patients was similar
      to that in developed countries; however, only a small proportion of eligible
      patients received the recommended VTE prophylaxis. Our findings highlight the
      need for dissemination and implementation of appropriate VTE prophylaxis
      guidelines in China.

PMID- 20688360
TI  - Biological distinctions between juvenile nasopharyngeal angiofibroma and vascular
      malformation: an immunohistochemical study.
AB  - The exact nature of juvenile nasopharyngeal angiofibroma (JNA) is still in
      dispute. In recent years, the main controversy of its nature has focused on
      hemangioma and vascular malformation. In this study, the immunolocalization of
      vascular endothelial growth factor (VEGF), VEGF receptor-1/fms-like tyrosine
      kinase-1 (VEGFR-1/Flt-1), VEGF receptor-2/fetal liver kinase-1 (VEGFR-2/Flk-1),
      proliferating cell nuclear antigen (PCNA), and CD34 was investigated in 28 cases
      of JNA and 20 cases of orbital cavernous hemangiomas (OCH). The immunostaining
      levels of VEGF, Flt-1, and Flk-1 were higher and more frequent in vascular
      endothelial cells of JNA than those of OCH (p<0.05). The average microvessel
      density (MVD) marked by CD34 in JNA was (49.3 +/- 9.1)/HPF (high power field),
      which was higher than OCH (29.1 +/- 6.7)/HPF (p<0.05). Immunoreactivity of PCNA
      was localized in both endothelial and stromal cell components of JNA, but was
      predominantly seen in the stromal cells. However, no PCNA immunoreactivity was
      identified in any of the stromal and endothelial cells in cases of OCH. The
      immunostaining levels of CD34, VEGF, Flt-1, Flk-1, and PCNA in JNA were higher
      than those in OCH. These data support the view that JNA has biological
      characteristics of an angiogenic histogenetic tumor. In the future, anti
      angiogenic therapy may represent a novel treatment strategy for JNA.

PMID- 20688361
TI  - Progress in ovarian cancer trials: the GCIG consensus model--is bigger, better?

PMID- 20688362
TI  - Periostin promotes ovarian cancer angiogenesis and metastasis.
AB  - OBJECTIVE: Perostin (PN) has been found to be overexpressed in a variety of human
      malignancies including ovarian cancer. In the present study, we investigated PN
      expression status in a large cohort of ovarian tumors with the focus on
      biological influence of PN related on ovarian tumor angiogenesis and metastasis.
      METHODS: PN expression was determined by cDNA microarray, PN northern blot and PN
      IHC tissue array analyses. Exogenous PN expression in ovarian cancer cells OVCAR
      3 and OV2008 were achieved through retroviral transfection and confirmed by PN
      western blot and ELISA. The effects of exogenous PN expression on tumor
      angiogenesis and metastatic growth were accessed in orthotopic mouse models. The
      in vitro cell adhesion, migration and invasion assays were performed to
      investigate the potential mechanisms involved in PN's in vivo effects. RESULTS:
      PN was frequently overexpressed in ovarian tumors. Higher PN levels significantly
      correlated with clinical late stages (III/IV) and cancer recurrence. PN was
      produced by engineered PN-overexpressing cells at levels comparable to that of
      A2780 cells, an ovarian carcinoma cell line with endogenous PN expression. PN
      overexpression did not change cell growth rates in vitro; however it
      significantly promoted intraperitoneal tumor metastatic growth in immunodeficient
      mice, which was associated with increased tumor angiogenesis and decreased tumor
      cell apoptosis. In vitro purified PN promoted cell adhesion, migration, and
      invasion of both human umbilical endothelial cells (HUVECs) and/or ovarian cancer
      cells. CONCLUSIONS: Our data indicate PN plays a critical role in both ovarian
      tumor angiogenesis and metastasis. Thus PN may represent a clinically effective
      new target for therapy of ovarian cancer.

PMID- 20688363
TI  - Long-term outcome and natural history of uterine adenosarcomas.
AB  - OBJECTIVE: Adenosarcomas are rare tumors composed of a benign epithelium in
      combination with a malignant mesenchymal component. We examined the natural
      history of uterine adenosarcomas and compared the outcome of uterine adenosarcoma
      and carcinosarcoma. METHODS: Patients with uterine adenosarcomas and
      carcinosarcomas registered in the Surveillance, Epidemiology, and End Results
      database between 1988 and 2006 were examined. Survival was analyzed using Cox
      proportional hazards model and the Kaplan-Meier method. RESULTS: A total of 5496
      patients including 544 (10%) with adenosarcomas were identified. Patients with
      adenosarcomas tended to be younger and were more likely to have early-stage
      tumors (p<0.0001) In a multivariate model patients with adenosarcomas were 65%
      (HR=0.35; 95% CI, 0.28-0.45) less likely to die from their tumors than women with
      carcinosarcomas. Five-year survival was 79% (95% CI, 75-84%) for stage I
      adenosarcomas and 51% (95% CI, 49-54%) for carcinosarcomas. For stage III
      disease, 5-year survival for adenosarcomas was 48% (95% CI, 29-65%) vs. 24% (95%
      CI, 20-27%) for carcinosarcomas. CONCLUSION: The majority of women with uterine
      adenosarcoma present with early-stage tumors and have a favorable outcome.
      Despite the overall favorable prognosis for most patients, survival is only 63
      69% for women whose tumors invade into the wall of the uterus and lower than 50%
      for disease spread beyond the uterus.

PMID- 20688364
TI  - Symptom research in gynecologic oncology: a review of available measurement
      tools.
AB  - OBJECTIVE: Cancer and its treatment produce multiple symptoms that significantly
      distress patients and impair function. Effective symptom management requires
      effective symptom assessment. A variety of measurement instruments have been
      created to identify symptoms in oncology practice. Here we review symptom
      assessment measures available for gynecologic cancers. METHODS: A systematic
      literature search was performed to identify articles on symptom assessment and
      quality-of-life instruments in gynecologic oncology. Articles were accessed
      through searches performed in PubMed, MEDLINE, CINAHL Plus, and the Cochrane
      Library. Studies were selected if they described development of symptom
      assessment tools for diagnosis and measurement of symptoms of gynecologic cancers
      and treatments. We also included studies using quality-of-life measurement tools
      that contained symptom items. RESULTS: Nine studies examined symptom assessment,
      quality-of-life assessment, or symptom indexes for various gynecologic cancers.
      Studies varied in design, patient profiles, symptoms assessed, and outcomes
      measured. Meta-analysis was not performed due to heterogeneity in the studies.
      CONCLUSION: Although pain is well-studied and well-characterized, other disease
      specific and general systemic symptoms of gynecologic cancers need better
      understanding and assessment. Accordingly, assessment of symptoms throughout the
      course of disease is crucial for treatment decisions and outcomes monitoring for
      patients with gynecologic cancer. This is especially true for survivors of
      gynecologic cancer, for patients whose treatment was unsuccessful, or for
      choosing between treatments with comparable survival outcomes. However,
      measurement and assessment of cancer-related symptoms is challenging because of
      the complex interaction between disease progression, multi-modality treatments,
      and symptoms. In this review, we evaluate the currently available symptom
      assessment tools for gynecologic cancers, along with quality-of-life assessment
      tools that include symptom items, and we give recommendations for further
      research.

PMID- 20688365
TI  - Prognostic significance of preoperative plasma fibrinogen in endometrial cancer.
AB  - OBJECTIVE: To investigate the prognostic significance of preoperative plasma
      fibrinogen concentration, with particular focus on tumor dissemination and nodal
      involvement, in a substantial cohort of patients with endometrial cancer.
      METHODS: The study population comprised 336 women with endometrial cancer who
      underwent surgical staging at two tertiary institutions, from 2000 to 2009.
      Pretreatment plasma samples from the study cohort were assayed for fibrinogen by
      the Clauss assay. Information on demographics, laboratory testing, histopathology
      and follow-up was gathered from databases of prospectively collected data.
      Factors associated with survival were identified in a Cox proportional hazards
      model. Univariate and multivariate analyses were used to evaluate predictors of
      extrauterine disease and nodal metastasis. RESULTS: One-hundred-thirty-seven
      (40.8%) patients exhibited preoperative hyperfibrinogenemia. Univariate analysis
      demonstrated that histological type, tumor grade, depth of myometrial invasion,
      surgical stage, patient age, and hyperfibrinogenemia affect disease-free (DFS)
      and overall survival rates significantly. When these variables were entered
      simultaneously into a Cox regression model, raised preoperative levels of plasma
      fibrinogen retained significance as poor prognosticator of DFS (HR 2.0, 95%CI 1.1
      3.6) and overall survival (HR 2.7, 95%CI 1.3-5.5). Preoperative
      hyperfibrinogenemia was an independent determinant of extrauterine disease (OR
      2.7, 95%CI 1.3-5.6). In the subcohort of women with endometrioid histology,
      increased fibrinogen concentration at presentation was predictive of pelvic nodal
      involvement (OR 3.6, 95%CI 1.1-11.7). CONCLUSION: Plasma fibrinogen level may be
      of value in the prediction of outcome, improve the stratification of endometrial
      cancer patient, at diagnosis, based on their risk of recurrence, and possibly
      alter their treatment accordingly.

PMID- 20688366
TI  - Methods of estrus detection and correlates of the reproductive cycle in the sun
      bear (Helarctos malayanus).
AB  - The objective was to explore multiple methods for detecting and characterizing
      the reproductive cycle of the sun bear (Helarctos malayanus). Thirteen H. m.
      euryspilus females, loaned from the Malaysian government to US zoos, were used.
      Fecal metabolite concentrations of estrogen and progesterone were compared to
      vaginal cytology, changes in genital appearance, and behavior (videotapes and
      zookeeper observations). Cytology and video behavior were characterized during
      five hormonally defined states: high, low, and baseline progesterone, estrus, and
      high estrogen. Among states, there were significant differences in cytology and
      behavior. Sexual, affiliative, and stereotypic behaviors were highest during
      estrus, whereas affiliative and social behaviors were lowest during high
      progesterone. In this captive breeding population, 30.8% of females cycled two or
      three times a year, 30.8% cycled once a year, and 38.5% did not cycle during this
      study. Inter-estrus intervals were (mean +/- SEM) 115.7 +/- 6.3 d (range, 101
      131). Spearman rank correlations were significant between both ordinal sexual and
      affiliative behaviors and vulva swelling and color. Sexual behavior was
      significantly positively correlated with superficial and keratinized cells, but
      negatively correlated with parabasal and basophilic cells in cycling females
      (opposite pattern for appetitive behavior). In conclusion, data for cytology,
      vulva changes and behavior were consistent with, and complementary to, hormonal
      data; collectively, they delineated estrus and identified specific reproductive
      types.

PMID- 20688367
TI  - Effect of increasing zinc sulphate concentration during in vitro maturation of
      bovine oocytes.
AB  - The objective was to investigate the effects of supplementary zinc (Zn) during in
      vitro maturation (IVM) of bovine oocytes. The DNA damage in cumulus cells was low
      with supplemental Zn concentrations of 1.1 and 1.5 MUg/mL in the IVM medium (mean
      +/- SEM index of DNA damage was 67.52 +/- 9.32, 68.52 +/- 13.34, 33.80 +/- 4.89,
      and 34.65 +/- 7.92 for supplementation with 0, 0.7, 1.1, and 1.5 MUg/mL Zn,
      respectively; P < 0.01). Total glutathione concentrations did not differ
      following Zn supplementation of 1.1 and 1.5 MUg/mL (3.7 +/- 0.4 vs. 4.0 +/- 0.5
      pmol, respectively, in oocytes; and in cumulus cells, 0.5 +/- 0.04 nmol/10(6)
      cells, combined for both treatments), but were greater (P < 0.01) than
      supplementation with 0.7 MUg/mL (1.8 +/- 0.5 pmol in oocytes and 0.2 +/- 0.02
      nmol/10(6) cumulus cells). Cleavage rate increased (P < 0.05) when Zn was added
      to the IVM medium at any concentration (67.16 +/- 1.17, 73.15 +/- 1.15, 74.05 +/-
      1.23, and 72.76 +/- 0.74 for 0, 0.7, 1.1, and 1.5 MUg/mL Zn). For these
      concentrations, subsequent embryo development to the blastocyst stage was 17.83
      +/- 2.15, 21.95 +/- 0.95, 27.65 +/- 1.61, and 30.33 +/- 2.78%, highest (P < 0.01)
      in oocytes matured with 1.5 MUg/mL Zn. There was an increase (P < 0.05) in mean
      cell number per blastocyst obtained from oocytes matured with 1.1 and 1.5 MUg/mL
      Zn relative to 0 Zn (IVM alone) and 0.7 MUg/mL Zn. In conclusion, Zn during
      oocytes maturation significantly affected intracellular GSH content and DNA
      integrity of cumulus cells, and improved preimplantational embryo development. We
      inferred that optimal embryo development to the blastocyst stage was partially
      dependent on the presence of adequate Zn concentrations.

PMID- 20688368
TI  - Bluetongue virus serotype 8 (BTV-8) infection reduces fertility of Dutch dairy
      cattle and is vertically transmitted to offspring.
AB  - In 2007, BTV-8 re-emerged for the second year in the Netherlands and caused
      morbidity and increased mortality in cattle herds. In addition, cattle farmers
      reported reduced fertility in their cows. For this study, fifteen herds that were
      not vaccinated were selected. These were matched to 10 vaccinated herds by
      geographic region. At the start of the study, in July 2008, all cattle in the non
      vaccinated herds >1 year old were sampled. All seronegative cows entered the
      study program and blood samples from these cows were tested for antibodies
      against BTV-8 in an ELISA. Cows were sampled at intervals of three weeks and
      sampling was stopped once a cow tested seropositive. Sampling ceased in all
      remaining cows in December 2008. Newborn calves originating from infected dams or
      from vaccinated dams were tested by PCR for BTV-8. Fertility data were obtained
      from the Royal Dutch Cattle Syndicate (CRV). Multi-level generalized latent and
      linear models were used for analyses. In 2008, 185 (17.2%) out of 1,074 initially
      seronegative non-vaccinated cattle seroconverted and were assumed to be infected
      with BTV-8. Infected cows were 5 (95% CI: 1.9-14.3) times more likely to return
      for insemination within 56 days after first insemination. In addition, these cows
      needed 1.7 (95% CI: 1.4-2.0) times more inseminations for an assumed pregnancy,
      and needed 2.5 (95% CI: 2.4-2.6) times more days between first and last
      insemination compared to the period prior to seroconversion and compared to cows
      not infected by BTV-8 in 2008. No association between BTV-8 infection and the
      chance to abort between 100 and 260 days after last insemination was found. In
      total, 48 calves originating from infected cows were tested by PCR for the
      presence of BTV-8. Ten (20.8%) out of these 48 calves were born PCR-positive.
      None of 256 calves from vaccinated dams tested PCR-positive. Further, cows
      infected during the second half of gestation had a 15.5 times (95% CI: 1.3-190.4)
      higher chance of a PCR-positive newborn calf compared to cows infected in the
      first half of gestation. This study showed that BTV-8 has a negative effect on
      fertility of dairy cattle.

PMID- 20688369
TI  - Sperm treatment affects capacitation parameters and penetration ability of
      ejaculated and epididymal boar spermatozoa.
AB  - This work was designed to study how this ability is affected by different sperm
      treatments routinely used for in vitro fertilization (IVF) assay. In this study,
      boar sperm samples from epididymal or ejaculated origin were processed by three
      different methods: left unwashed (NW group), washed in Dulbecco's phosphate
      buffered saline supplemented with 0.1% BSA (BSA group), and washed on a
      Percoll((r)) gradient (PERCOLL group). After preparation of semen samples,
      changes in motility patterns were studied by CASA, calcium uptake by
      spectrofluorimetry, and ROS generation, spontaneous acrosome reaction, and lipid
      disorder by means of flow cytometry. Finally IVF assays were also performed with
      the different semen samples and penetrability results evaluated at 2 and 4 h post
      insemination (hpi). Independently of the sperm treatment, epididymal spermatozoa
      showed higher values of progressive motility, percentage of live cells with low
      lipid disorder, and penetration ability at 4 hpi than the corresponding
      ejaculated spermatozoa. Ejaculated spermatozoa showed higher levels of calcium
      uptake, ROS generation and percentage of spontaneous acrosome reaction than
      epididymal sperm. Regarding sperm treatments, PERCOLL group showed the highest
      values for some motility parameters (linearity of the curvilinear trajectory,
      straightness, and average path velocity/curvilinear velocity), ROS generation and
      penetration ability at 2 and 4 hpi; however this same group showed the lowest
      values for sperm curvilinear velocity and lateral head displacement. From all
      experimental groups, ejaculated-PERCOLL-treated spermatozoa showed the highest
      fertilization ability after 2 hpi. Results suggest that capacitation pathways can
      be regulated by suitable treatments making the ejaculated sperm able to reach
      capacitation and fertilize oocytes in similar levels than epididymal spermatozoa,
      although most of the studied capacitation-associated changes do not correlate
      with this ability.

PMID- 20688370
TI  - Fragmentation dynamics of frozen-thawed ram sperm DNA is modulated by sperm
      concentration.
AB  - This study investigated the hypothesis that post-thaw incubation of ram sperm at
      high concentrations results in a faster rate of DNA fragmentation than when sperm
      are incubated at a lower concentration. Ejaculates from 10 rams were frozen
      thawed, prepared in sperm concentrations of 100, 50, 25, 12, and 6 * 106
      sperm/mL, and incubated for 6 h at 37  degrees C. Sperm DNA fragmentation was
      assessed using the sperm chromatin dispersion test (Sperm-Halomax(r)) at 1, 3, 4,
      and 6 h of incubation at 37  degrees C. On fitting a binary logistic regression
      with a cubic over time and treating ram and dilution levels as factors, there
      were significant effects with respect to the ram, dilution and time (all P-values
      were very much smaller than 0.001). Therefore, DNA fragmentation dynamics of
      incubated frozen-thawed ram sperm were not only dependent on the inherent sperm
      DNA fragmentation expressed immediately after thawing, but also on the
      concentration of sperm incubated in the sample. Although there was evidence of
      individual ram variation in SDF during the incubation period, the general finding
      of the current study was that lower sperm concentrations resulted in a slower
      rate of DNA fragmentation These findings have important implications for the post
      thaw manipulation of ram sperm used for AI and advanced reproductive procedures
      that use sperm at low concentrations. Our data also emphasised the highly dynamic
      nature of sperm DNA fragmentation and the importance of conducting the procedure
      in a standardised manner.

PMID- 20688371
TI  - Pregnancies and piglets from large white sow recipients after two transfer
      methods of cloned and transgenic embryos of different pig breeds.
AB  - The aim of this study was to report from a larger study with pregnancy and
      delivery results after transfer of cloned transgenic/non-transgenic Large White
      or minipig embryos to Large White sow recipients. The effect of both total
      numbers of transferred embryos as well as site of their deposition (uni- vs. bi
      lateral) was studied. Four to five days after natural heat, 85 Large White (LW)
      sows received Day 5 or 6 handmade cloned embryos. Large White embryos were non
      transgenic and were transferred to 36 recipients, while 49 recipients each
      received Minipig embryos, either non-transgenic or with 1 of 4 types of
      transgenes. Furthermore, the number of embryos transferred was in two categories,
      as 46 recipients received 40-60 embryos while 39 received 60-120 embryos.
      Finally, in 59 of the recipients embryos were transferred to one of the uterine
      horns (unicornual) while 26 other recipients had embryos transferred to both
      uterine horns (bicornual). The overall pregnancy rate was 55% with an abortion
      rate of 26% resulting in 41% deliveries with no difference between LW and Minipig
      embryos and no difference between transgenic and non-transgenic Minipig embryos.
      Transfer of 60-120 embryos resulted in more pregnancies and deliveries (62%) than
      <60 embryos (24%). The mean litter size was 5.1 +/- 0.5 and after transfer of 60
      120 embryos significantly higher (6.0 +/- 0.5) than after transfer of <60 embryos
      (3.5 +/- 0.8). Also, the bicornual transfer resulted in significantly higher
      delivery rate (74% vs. 44%) and mean litter size (6.1 +/- 0.7 vs. 4.2 +/- 0.6)
      than the unicornual. The mean rate of piglets/transferred embryos was 7.3 +/-
      0.6% while the mean rate of piglets/reconstructed embryos was 179/18,000 = 1%
      with no difference between breeds or number of embryos transferred. The overall
      perinatal mortality rate was 49%, and it was significantly lower in LW piglets
      (20/59 = 34%) than in Minipiglets (67/120 = 56%) (vs. 10-15% in normal piglets at
      the farm) and the total rate of piglets with one or more malformation was 22%,
      and lower in LW (12%) than in Minipiglets (28%). This study demonstrate that
      although the perinatal mortality was rather high, an acceptable birth rate can be
      achieved after transfer to LW recipients of cloned LW embryos as well as cloned,
      transgenic/non-transgenic Minipig embryos. Furthermore, the pregnancy rate and
      litter size were correlated to the number of embryos transferred and to bicornual
      transfer.

PMID- 20688372
TI  - Expression of messenger RNAs for insulin-like growth factors and their receptors
      in bovine fetuses at early gestation from embryos produced in vivo or in vitro.
AB  - The objective of this study was to determine the effects of in vitro embryo
      production on physical development and levels of expression of mRNAs for insulin
      like growth factor (IGF) ligands (IGF1, IGF2), their receptors (IGF1R, IGF2R),
      and IGF binding protein-2 (IGFBP2) in bovine fetuses during early gestation. In
      vivo embryos were recovered from superovulated Holstein cows. For production of
      embryos in vitro, Holstein oocytes were matured, fertilized, and subsequently
      cultured in M199 with 10% serum to 168 hpi. On Day 70 of gestation, fetuses (in
      vivo, n = 14; in vitro, n = 13) were recovered, serum samples collected, and
      physical measurements recorded. Semi-quantitative RT-PCR assays were used to
      determine the levels of expression of mRNAs for IGF1, IGF2, IGF1R, and IGF2R in
      fetal liver and skeletal muscle. Western blots were used to assess levels of
      IGFBP2 in fetal serum. Fetal body weight did not differ with treatment; however,
      production of embryos in vitro was associated with decreased crown-nose length
      and a tendency for increased paired kidney weight, which became significant when
      expressed on a per bodyweight basis. There was no effect of treatment on levels
      of IGFBP2 in fetal serum. Levels of IGF1 mRNA in fetal liver were decreased (P <
      0.001) in the in vitro group. Levels of IGF2R mRNA in both liver and skeletal
      muscle were also decreased (P < 0.01) in fetuses from the in vitro group. In
      summary, fetuses at Day 70 of gestation from embryos produced in vitro had
      shortened crown-nose length and increased kidney weight on a per bodyweight
      basis, as well as decreased expression of mRNAs for IGF1 in liver and IGF2R in
      both liver and skeletal muscle, compared with fetuses from embryos produced in
      vivo. In conclusion, in vitro embryo culture was associated with subtle changes
      in fetal development as well as altered expression of both imprinted and non
      imprinted genes.

PMID- 20688373
TI  - Effect of the addition of insulin-transferrin-selenium and/or L-ascorbic acid to
      the in vitro maturation of prepubertal bovine oocytes on cytoplasmic maturation
      and embryo development.
AB  - This study examines the effects of adding insulin-transferrin-selenium (ITS)
      and/or L-ascorbic acid (ASC) to a conventional medium for maturing prepubertal
      calf oocytes on chromosome organization, cortical granule (CG) distribution, and
      embryo development to the blastocyst stage. Cumulus-oocyte complexes (COCs) were
      matured in medium TCM 199 containing PVA and EGF (control), and supplemented with
      ITS and/or ASC for 12 or 24 h at 38.5  degrees C in a 5% CO(2) atmosphere. Calf
      oocytes matured with ITS + ASC or ASC for 12 h showed significantly higher
      percentages of peripherally distributed CG (83.3% and 86.2% respectively) than
      control oocytes (71.4%) or those matured with ITS alone (71.4%). No effects on
      chromosome organization were detected. Conversely, 24 h of supplementation did
      not affect CG distribution patterns, while the addition of ASC gave rise to
      significantly higher percentages of oocytes showing a normal alignment of their
      chromosomes (72.9%) compared to controls (58.7%). At 48 hpi, similar cleavage
      rates were observed among treatments regardless of the treatment time. However,
      the presence of ITS + ASC for 12 h rendered significantly higher blastocyst rates
      than those recorded in the remaining groups. Supplementation for 24 h with ITS or
      ITS + ASC had no significant effects on the percentage of blastocysts obtained,
      while the presence of ASC significantly reduced the proportions of embryos
      developing to the blastocyst stage. Our data suggest that ITS plus L-ascorbic
      acid supplementation during the first 12 h of in vitro maturation improves
      cytoplasm maturation and the developmental competence of embryos produced from
      prepubertal calf oocytes.

PMID- 20688374
TI  - Apoptotic and developmental effects of bovine Herpesvirus type-5 infection on in
      vitro-produced bovine embryos.
AB  - Bovine Herpesvirus type-5 (BoHV-5), which is potentially neuropathogenic, was
      recently described to be related with reproductive disorders in cows. The
      objective was to elucidate mechanisms involved in propagation of BoHV-5 in
      embryonic cells. For this purpose, bovine embryos produced in vitro were assayed
      for apoptotic markers after experimental infection of oocytes, in vitro
      fertilization, and development. Host DNA fragmentation was detected with a TUNEL
      assay, expression of annexin-V was measured with indirect immunofluorescence, and
      viral DNA was detected with in situ hybridization. Infective BoHV-5 virus was
      recovered from embryos derived from exposed oocytes after two consecutive
      passages on Madin-Darby bovine kidney (MDBK) cells. The viral DNA corresponding
      to US9 gene, localized between nucleotides 126243 to 126493, was detected in situ
      and amplified. There was no significant difference between the ratio of TUNEL
      stained nuclei and total cells in good quality blastocysts (0.87 +/- 0.05, mean
      +/- SD), but there were differences (P < 0.05) between infected (0.18 +/- 0.05)
      and uninfected blastocysts (0.73 +/- 0.07). The Annexin-V label was more intense
      in uninfected embryos (0.79 +/- 0.04; P < 0.05). The quality of infected and
      uninfected embryos was considered equal, with no significant effect on embryonic
      development. In conclusion, we inferred that BoHV-5 infected bovine oocytes,
      replicated, and suppressed some apoptotic pathways, without significantly
      affecting embryonic development.

PMID- 20688376
TI  - A behavioural scale to measure ease of farrowing in sows.
AB  - Farrowing is one of the most critical phases in pig production, as it has an
      impact on neonatal pig survival. Assessing the ease of farrowing can improve the
      management of sows and thus increase litter survival. The aims of this study
      were: 1) to develop an ease of farrowing score (EFS) in sows based on the
      behaviour of the sows and their piglets, and 2) to determine the relationship
      between the EFS and productive, physiological, and subjective parameters. Eighty
      hybrid (Large White * Landrace) sows from first to seventh parity housed in
      individual crates were used. An EFS was constructed using the total duration of
      farrowing, the birth interval, the total time standing or sitting, the number of
      position changes during the day before and the day of farrowing, the sow posture
      at birth, the viability and the position of the piglets at birth (head or back
      born). Moreover, rectal temperature at 90 min after farrowing, a four categorical
      subjective visual assessment (VA) of farrowing and litter size (piglets born
      alive, stillborn and mummified foetus) were recorded. A common factor analysis
      model yielded five factors with an eigenvalue higher than 0.95 that accounted for
      75.05% of the total variation between individuals. The three main factors were
      "farrowing duration", "sow posture", and "sow activity" of sows and explained
      23.44%, 15.67%, and 14.23% of the variance, respectively. Primiparous sows had
      higher values for factor 3 (sow activity) than multiparous sows (P = 0.02). Sows
      without stillborn or mummification foetus showed higher values of EFS than sows
      with at least one stillborn or mummification foetus (P = 0.06 and 0.01,
      respectively). Sows that received a visual assessment of 3 and 4 showed higher
      values of EFS than sows that received a VA of 1 and 2 (P = 0.0017). The EFS
      appears to be a good behavioural scale to measure ease of farrowing in sows kept
      in individual farrowing crates. Duration of farrowing, sow position, and presence
      of stillborn piglets and mummified foetuses appear to be important ease of
      farrowing indicators.

PMID- 20688375
TI  - The multi-potentiality of skin-derived stem cells in pigs.
AB  - Multipotent skin-derived stem cells represent neural-crest derived precursors
      which have neural and mesodermal potency and can generate neurons, glias, smooth
      muscle cells, and adipocytes. Transcriptional profiling studies show that both
      intrinsic programs and extrinsic signaling pathways mediate their neural and
      mesodermal potency. In addition, recent progress implies that skin-derived stem
      cells may have a broader developmental potency than previously expected, of which
      is their potential to generate germline cells in vitro. In this review, we
      discuss the transcriptional profiling of multipotency and neural crest-derived
      characteristics of skin-derived stem cells, and argue for their potential germ
      line competency in the view of nuclear and cellular reprogramming.

PMID- 20688377
TI  - Current status and applications of somatic cell nuclear transfer in dogs.
AB  - Although somatic cell nuclear transfer (SCNT) technology and applications are
      well developed in most domesticated and laboratory animals, their use in dogs has
      advanced only slowly. Many technical difficulties had to be overcome before
      preliminary experiments could be conducted. First, due to the very low efficiency
      of dog oocyte maturation in vitro, in vivo matured oocytes were generally used.
      The nucleus of an in vivo matured oocyte was removed and a donor cell (from fetal
      or adult fibroblasts) was injected into the oocyte. Secondly, fusion of the
      reconstructed oocytes was problematic, and it was found that a higher electrical
      voltage was necessary, in comparison to other mammalian species. By transferring
      the resulting fused oocytes into surrogate females, several cloned offspring were
      born. SCNT was also used for producing cloned wolves, validating reproductive
      technologies for aiding conservation of endangered or extinct breeds. Although
      examples of transgenesis in canine species are very sparse, SCNT studies are
      increasing, and together with the new field of gene targeting technology, they
      have been applied in many fields of veterinary or bio-medical science. This
      review summarizes the current status of SCNT in dogs and evaluates its potential
      future applications.

PMID- 20688378
TI  - Percoll gradient separation of cryopreserved common carp spermatozoa to obtain a
      fraction with higher motility, velocity and membrane integrity.
AB  - We attempted to select a fraction of common carp, Cyprinus carpio spermatozoa
      that best survived a conventional freeze/thaw procedure, by centrifugation of
      frozen/thawed sperm through a Percoll gradient (45% and 90%). The proportion of
      motile spermatozoa (65.81 +/- 5.19%), their velocity (77.58 +/- 31.07 MUm/sec),
      and membrane integrity (83.66 +/- 4.38% intact) were significantly higher in
      separated sperm than in whole samples (motility 23.36 +/- 2.98%, velocity 55.55
      +/- 19.03 MUm/sec, and membrane integrity 57.92 +/- 4.65%). Our results
      demonstrated that Percoll gradient centrifugation shows promise as a technique
      for selecting high quality cryopreserved fish spermatozoa, which could be useful
      for cryobiological research. Further studies are needed to evaluate the
      potentially higher fertilizing ability of the separated spermatozoa.

PMID- 20688379
TI  - Variation in instrument-based color coordinates of esthetic restorative materials
      by measurement method-A review.
AB  - OBJECTIVES: Optical properties of an object are determined visually or
      instrumentally. Although instrumental measurement provides objective and
      quantitative color coordinates, these values vary by the measurement method such
      as specimen and background conditions, instrument settings and illuminant. The
      objective of this study was to review the influence of the measurement method on
      the instrumental color coordinates of esthetic dental restorative materials.
      METHODS: Published reports on the measurement method dependent color variations
      of esthetic restorative materials were reviewed. RESULTS: Surface roughness
      influences the color coordinates differently by the surface roughness range and
      the measurement geometry. Specimen thickness and the kind of illuminant influence
      the color coordinates, and the influence of background varied by specimen
      thickness. Therefore, the specular component excluded (SCE) geometry that
      reflects the surface condition of specimens is suggested as the correct
      measurement geometry. Surface roughness, thickness and layering of specimens, and
      the kind of illuminant should be stipulated in each measurement. There should be
      a standard for the color and gloss of the background. SIGNIFICANCE: Variables in
      instrumental color measurements should be stipulated to obtain consistent and
      comparable color coordinates, and a general guideline for instrumental color
      measurement of dental materials should be established.

PMID- 20688380
TI  - The requirement of zinc and calcium ions for functional MMP activity in
      demineralized dentin matrices.
AB  - The progressive degradation of resin-dentin bonds is due, in part, to the slow
      degradation of collagen fibrils in the hybrid layer by endogenous matrix
      metalloproteinases (MMPs) of the dentin matrix. In in vitro durability studies,
      the storage medium composition might be important because the optimum activity of
      MMPs requires both zinc and calcium. OBJECTIVE: This study evaluated the effect
      of different storage media on changes in matrix stiffness, loss of dry weight or
      solubilization of collagen from demineralized dentin beams incubated in vitro for
      up to 60 days. METHODS: Dentin beams (1mm*2mm*6mm) were completely demineralized
      in 10% phosphoric acid. After baseline measurements of dry mass and elastic
      modulus (E) (3-point bending, 15% strain) the beams were divided into 5 groups
      (n=11/group) and incubated at 37 degrees C in either media containing both zinc
      and calcium designated as complete medium (CM), calcium-free medium, zinc-free
      medium, a doubled-zinc medium or water. Beams were retested at 3, 7, 14, 30, and
      60 days of incubation. The incubation media was hydrolyzed with HCl for the
      quantitation of hydroxyproline (HOP) as an index of solubilization of collagen by
      MMPs. Data were analyzed using repeated measures of ANOVA. RESULTS: Both the
      storage medium and the storage time showed significant effects on E, mass loss
      and HOP release (p<0.05). The incubation in CM resulted in relatively rapid and
      significant (p<0.05) decreases in stiffness, and increasing amounts of mass loss.
      The HOP content of the experimental media also increased with incubation time but
      was significantly lower (p<0.05) than in the control CM medium, the recommended
      storage medium. CONCLUSIONS: The storage solutions used to age resin-dentin bonds
      should be buffered solutions that contain both calcium and zinc. The common use
      of water as an aging medium may underestimate the hydrolytic activity of
      endogenous dentin MMPs.

PMID- 20688382
TI  - Potential rates and environmental controls of denitrification and nitrous oxide
      production in a temperate urbanized estuary.
AB  - Denitrification may play a major role in inorganic nitrogen removal from
      estuarine ecosystems, particularly in those subjected to increased nitrate and
      organic matter loads. The Douro estuary (NW Portugal) suffers from both problems:
      freshwater input of nitrate and organic load from untreated wastewater
      discharges. To assess how these factors might control sediment denitrification, a
      12-month survey was designed. Denitrification potential and nitrous oxide (N(2)O)
      production were measured at different locations using the slurry acetylene
      blockage technique. Denitrification rate ranged from 0.4 to 38 nmol N g-1 h-1,
      increasing towards the river mouth following an urban pollution gradient. N(2)O
      production, a powerful greenhouse gas implicated on the destruction of the ozone
      layer, was significantly related with sediment organic matter and accounted for
      0.5-47% of the N gases produced. Additional enrichment experiments were
      consistent with the results found in the environment, showing that sediments from
      the upper less urban stretch of the estuary, mostly sandy, respond positively to
      carbon and, inversely, in organic rich sediments from the lower estuary, the
      denitrification potential was limited by nitrate availability. The obtained
      results confirmed denitrification as an important process for the removal of
      nitrate in estuaries. The presence of wastewater discharges appears to stimulate
      nitrogen removal but also the production of N(2)O, a powerful greenhouse gas,
      exacerbating the N(2)O:N(2) ratio and thus should be controlled.

PMID- 20688381
TI  - A chemical phosphorylation-inspired design for Type I collagen biomimetic
      remineralization.
AB  - OBJECTIVES: Type I collagen alone cannot initiate tissue mineralization. Sodium
      trimetaphosphate (STMP) is frequently employed as a chemical phosphorylating
      reagent in the food industry. This study examined the feasibility of using STMP
      as a functional analog of matrix phosphoproteins for biomimetic remineralization
      of resin-bonded dentin. METHODS: Equilibrium adsorption and desorption studies of
      STMP were performed using demineralized dentin powder (DDP). Interaction between
      STMP and DDP was examined using Fourier transform-infrared spectroscopy. Based on
      those results, a bio-inspired mineralization scheme was developed for chemical
      phosphorylation of acid-etched dentin with STMP, followed by infiltration of the
      STMP-treated collagen matrix with two etch-and-rinse adhesives. Resin-dentin
      interfaces were remineralized in a Portland cement-simulated body fluid system,
      with or without the use of polyacrylic acid (PAA) as a dual biomimetic analog.
      Remineralized resin-dentin interfaces were examined unstained using transmission
      electron microscopy. RESULTS: Analysis of saturation binding curves revealed the
      presence of irreversible phosphate group binding sites on the surface of the DDP.
      FT-IR provided additional evidence of chemical interaction between STMP and DDP,
      with increased in the peak intensities of the PO and P-O-C stretching modes.
      Those peaks returned to their original intensities after alkaline phosphatase
      treatment. Evidence of intrafibrillar apatite formation could be seen in
      incompletely resin-infiltrated, STMP-phosphorylated collagen matrices only when
      PAA was present in the SBF. SIGNIFICANCE: These results reinforce the importance
      of PAA for sequestration of amorphous calcium phosphate nanoprecursors in the
      biomimetic remineralization scheme. They also highlight the role of STMP as a
      templating analog of dentin matrix phosphoproteins for inducing intrafibrillar
      remineralization of apatite nanocrystals within the collagen matrix of
      incompletely resin-infiltrated dentin.

PMID- 20688383
TI  - A constitutive model for the warp-weft coupled non-linear behavior of knitted
      biomedical textiles.
AB  - Knitted textiles have been used in medical applications due to their high
      flexibility and low tendency to fray. Their mechanics have, however, received
      limited attention. A constitutive model for soft tissue using a strain energy
      function was extended, by including shear and increasing the number and order of
      coefficients, to represent the non-linear warp-weft coupled mechanics of coarse
      textile knits under uniaxial tension. The constitutive relationship was
      implemented in a commercial finite element package. The model and its
      implementation were verified and validated for uniaxial tension and simple shear
      using patch tests and physical test data of uniaxial tensile tests of four very
      different knitted fabric structures. A genetic algorithm with step-wise increase
      in resolution and linear reduction in range of the search space was developed for
      the optimization of the fabric model coefficients. The numerically predicted
      stress-strain curves exhibited non-linear stiffening characteristic for fabrics.
      For three fabrics, the predicted mechanics correlated well with physical data, at
      least in one principal direction (warp or weft), and moderately in the other
      direction. The model exhibited limitations in approximating the linear elastic
      behavior of the fourth fabric. With proposals to address this limitation and to
      incorporate time-dependent changes in the fabric mechanics associated with tissue
      ingrowth, the constitutive model offers a tool for the design of tissue
      regenerative knit textile implants.

PMID- 20688384
TI  - Mineralized human primary osteoblast matrices as a model system to analyse
      interactions of prostate cancer cells with the bone microenvironment.
AB  - Prostate cancer metastasis is reliant on the reciprocal interactions between
      cancer cells and the bone niche/micro-environment. The production of suitable
      matrices to study metastasis, carcinogenesis and in particular prostate
      cancer/bone micro-environment interaction has been limited to specific protein
      matrices or matrix secreted by immortalised cell lines that may have undergone
      transformation processes altering signaling pathways and modifying gene or
      receptor expression. We hypothesize that matrices produced by primary human
      osteoblasts are a suitable means to develop an in vitro model system for bone
      metastasis research mimicking in vivo conditions. We have used a decellularized
      matrix secreted from primary human osteoblasts as a model for prostate cancer
      function in the bone micro-environment. We show that this collagen I rich matrix
      is of fibrillar appearance, highly mineralized, and contains proteins, such as
      osteocalcin, osteonectin and osteopontin, and growth factors characteristic of
      bone extracellular matrix (ECM). LNCaP and PC3 cells grown on this matrix, adhere
      strongly, proliferate, and express markers consistent with a loss of epithelial
      phenotype. Moreover, growth of these cells on the matrix is accompanied by the
      induction of genes associated with attachment, migration, increased invasive
      potential, Ca(2+) signaling and osteolysis. In summary, we show that growth of
      prostate cancer cells on matrices produced by primary human osteoblasts mimics
      key features of prostate cancer bone metastases and thus is a suitable model
      system to study the tumor/bone micro-environment interaction in this disease.

PMID- 20688385
TI  - Contribution of physicochemical characteristics of nano-oxides to cytotoxicity.
AB  - To identify the key physicochemical properties of nano-oxides governing
      cytotoxicity, we investigate the contribution of the size, shape, morphology, and
      electronic properties of ten types of insulator (SiO(2), CeO(2) and Al(2)O(3))
      and semiconductor (ZnO and CuO) nano-oxides to cytotoxicity using the NIH3T3 and
      A549 cell lines as models. We find that the shape of the Al(2)O(3) (nanoparticle
      versus nanowhisker) and the morphology of the SiO(2) (porous versus non-porous
      nanoparticles) did not have obvious effect on the observed cytotoxicity, and the
      size of the nano-oxides cannot be regarded as an indicator of cytotoxicity. By
      contrast, we find that the cell viability exposed to the semiconductor nano
      oxides was much lower than that exposed to the insulator nano-oxides. Moreover,
      the Al-doped ZnO nanoparticle (NP) was more toxic than the non-doped ZnO NP,
      whereas the Al-doped CuO NP was less toxic than the non-doped CuO NP but more
      toxic than the Al(2)O(3) NP. Correspondingly, the valence band X-ray
      photoelectron spectra of the nano-oxides show the density of states of the Al
      doped ZnO NP (the Al-doped CuO NP) is higher (lower) than that of the non-doped
      ZnO NP (the non-doped CuO NP). These results suggest that the electronic
      properties of nano-oxides may play an important role in the observed
      cytotoxicity. The results have implications for selectively tailoring the toxic
      effect and establishing predictive models for the design of various types of
      nanomaterials with unique properties and for the understanding of interactions
      between nanomaterials with biological system.

PMID- 20688386
TI  - A synthetic elastomer based on acrylated polypropylene glycol triol with tunable
      modulus for tissue engineering applications.
AB  - As strategies for manipulating cellular behaviour in vitro and in vivo become
      more sophisticated, synthetic biomaterial substrates capable of reproducing
      critical biochemical and biophysical properties (or cues) of tissue micro
      environments will be required. Cytoskeletal tension has been shown to be highly
      deterministic of cell fate decisions, yet few synthetic biomaterials are capable
      of modulating cytoskeletal tension of adhered cells through variations in
      stiffness, at least in the ranges applicable to tissue properties (e.g., 1-100
      kPa), whilst also possessing other required properties, such as biodegradability,
      biocompatibility and processability. In this paper we describe a non-cytotoxic
      polymer system based on acrylated polypropylene glycol triol (aPPGT). This new
      elastomer system has tunable elastic moduli, is degradable, can be easily surface
      modified and can be manufactured into porous three dimensional scaffolds or
      micropatterned substrates. We demonstrate that the PPGT substrates can modulate
      hMSC morphology, growth, and differentiation, and that they can produce similar
      outcomes as observed for a non-degradable polyacrylamide substrate, confirming
      their utility as a degradable elastomer for tissue engineering and other
      biomedical applications.

PMID- 20688387
TI  - The role of biomaterials in the direction of mesenchymal stem cell properties and
      extracellular matrix remodelling in dermal tissue engineering.
AB  - Recently, a new generation of dermal equivalents (DE) was presented which are
      solely generated on a human fibroblast-derived dermal matrix. Since human
      mesenchymal stem cells from bone marrow (BM-MSC) and Wharton's Jelly of the
      umbilical cord (UC-MSC) are characterised by a distinct biosynthetic and
      paracrine activity, they are an appealing alternative approach for generating
      cell-based DE. This study compares the epithelial-mesenchymal interaction and
      extracellular matrix (ECM) remodelling of cell-based and collagen-based DE using
      fibroblasts, BM-MSC or UC-MSC, respectively, in co-culture with the keratinocyte
      cell line HaCaT. While fibroblast-based DE exhibit normal matrix synthesis,
      proliferation and differentiation of keratinocytes, mesenchymal stem cell-based
      DE resulted in excessive production of inhomogenous matrix aggregates, loss of
      polarisation of the epidermal cell layer and an inconstant paracrine activity. In
      contrast, collagen-embedded MSC revealed a homogenous growth pattern as well as a
      constant expression of growth factors and ECM proteins without a negative
      influence on the epidermal layer as shown by histology, electron microscopy,
      immunohistochemistry and realtime-RT-PCR. These results indicate the necessity of
      an instructive biomaterial-based scaffold to direct stem cell differentiation,
      proliferation, paracrine activity as well as regulation of ECM deposition.

PMID- 20688388
TI  - Differences between in vitro viability and differentiation and in vivo bone
      forming efficacy of human mesenchymal stem cells cultured on PCL-TCP scaffolds.
AB  - Human mesenchymal stem cells (hMSCs) possess great therapeutic potential for the
      treatment of bone disease and fracture non-union. Too often however, in vitro
      evidence alone of the interaction between hMSCs and the biomaterial of choice is
      used as justification for continued development of the material into the clinic.
      Clearly for hMSC-based regenerative medicine to be successful for the treatment
      of orthopaedic trauma, it is crucial to transplant hMSCs with a suitable carrier
      that facilitates their survival, optimal proliferation and osteogenic
      differentiation in vitro and in vivo. This motivated us to evaluate the use of
      polycaprolactone-20% tricalcium phosphate (PCL-TCP) scaffolds produced by fused
      deposition modeling for the delivery of hMSCs. When hMSCs were cultured on the
      PCL-TCP scaffolds and imaged by a combination of phase contrast, scanning
      electron and confocal laser microscopy, we observed five distinct stages of
      colonization over a 21-day period that were characterized by cell attachment,
      spreading, cellular bridging, the formation of a dense cellular mass and the
      accumulation of a mineralized extracellular matrix when induced with osteogenic
      stimulants. Having established that PCL-TCP scaffolds are able to support hMSC
      proliferation and osteogenic differentiation, we next tested the in vivo efficacy
      of hMSC-loaded PCL-TCP scaffolds in nude rat critical-sized femoral defects. We
      found that fluorescently labeled hMSCs survived in the defect site for up to 3
      weeks post-transplantation. However, only 50% of the femoral defects treated with
      hMSCs responded favorably as determined by new bone volume. As such, we show that
      verification of hMSC viability and differentiation in vitro is not sufficient to
      predict the efficacy of transplanted stem cells to consistently promote bone
      formation in orthotopic defects in vivo.

PMID- 20688389
TI  - Protease degradable tethers for controlled and cell-mediated release of
      nanoparticles in 2- and 3-dimensions.
AB  - Strategies to control the release rate of bioactive signals from tissue
      engineering scaffolds are essential for tissue regeneration and tissue
      engineering applications. Here we report on a strategy to achieve temporal
      control over nanoparticle release from biomaterials using cell-secreted
      proteases. This cell-triggered release approach utilizes peptides that are
      degraded by matrix metalloproteinases (MMPs) at different rates to immobilize
      nanoparticles directly to the biomaterial surface. Thus, the peptide-immobilized
      nanoparticles are released with temporal control through the action of cell
      released MMPs. We found that release rates of peptide-immobilized nanoparticles
      were a function of peptide sensitivity to proteases, the number of tethers
      between the nanoparticle and the surface and the concentration of proteases used
      to induce release. Cellular internalization of the peptide-immobilized
      nanoparticles was also a function of the peptide sensitivity to proteases, the
      number of tethers between the nanoparticle and the surface and MMP expression
      profile of the cells. Similar trends were observed for peptide-immobilized
      nanoparticles inside micro-porous hydrogels, indicating protease sensitive
      tethers are effective in controlling release rate and internalization of
      nanoparticles. Such a temporal delivery strategy of nanoparticles loaded with
      therapeutic payloads (e.g. protein, DNA, siRNA) can be an ideal means to guide
      tissue formation.

PMID- 20688390
TI  - A silk platform that enables electrophysiology and targeted drug delivery in
      brain astroglial cells.
AB  - Astroglial cell survival and ion channel activity are relevant molecular targets
      for the mechanistic study of neural cell interactions with biomaterials and/or
      electronic interfaces. Astrogliosis is the most typical reaction to in vivo brain
      implants and needs to be avoided by developing biomaterials that preserve
      astroglial cell physiological function. This cellular phenomenon is characterized
      by a proliferative state and altered expression of astroglial potassium (K(+))
      channels. Silk is a natural polymer with potential for new biomedical
      applications due to its ability to support in vitro growth and differentiation of
      many cell types. We report on silk interactions with cultured neocortical
      astroglial cells. Astrocytes survival is similar when plated on silk-coated glass
      and on poly-D-lysine (PDL), a well known polyionic substrate used to promote
      astroglial cell adhesion to glass surfaces. Comparative analyses of whole-cell
      patch-clamp experiments reveal that silk- and PDL-coated cells display
      depolarized resting membrane potentials (-40 mV), very high input resistance, and
      low specific conductance, with values similar to those of undifferentiated glial
      cells. Analysis of K(+) channel conductance reveals that silk-astrocytes express
      large outwardly delayed rectifying K(+) current (K(DR)). The magnitude of K(DR)
      in PDL- and silk-coated astrocytes is similar, indicating that silk does not
      alter the resting K(+) current. We also demonstrate that guanosine- (GUO)
      embedded silk enables the direct modulation of astroglial K(+) conductance in
      vitro. Astrocytes plated on GUO-embedded silk are more hyperpolarized and express
      inward rectifying K(+) conductance (K(ir)). The K(+) inward current increases and
      this is paralleled by upregulation and membrane polarization of K(ir)4.1 protein
      signal. Collectively these results indicate that silk is a suitable biomaterial
      platform for the in vitro studies of astroglial ion channel responses and related
      physiology.

PMID- 20688391
TI  - Mesenchymal stem cells as cellular vehicles for delivery of nanoparticles to
      brain tumors.
AB  - The prognosis of patients with malignant glioma remains extremely poor, despite
      surgery and improvements in radio- and chemo-therapies. Nanotechnologies
      represent great promise in glioma therapy as they protect therapeutic agent and
      allow its sustained release. However, new paradigms allowing tumor specific
      targeting and extensive intratumoral distribution must be developed to
      efficiently deliver nanoparticles (NPs). Knowing the tropism of mesenchymal stem
      cells (MSCs) for brain tumors, the aim of this study was to obtain the proof of
      concept that these cells can be used as NP delivery vehicles. Two types of NPs
      loaded with coumarin-6 were investigated: poly-lactic acid NPs (PLA-NPs) and
      lipid nanocapsules (LNCs). The results show that these NPs can be efficiently
      internalized into MSCs while cell viability and differentiation are not affected.
      Furthermore, these NP-loaded cells were able to migrate toward an experimental
      human glioma model. These data suggest that MSCs can serve as cellular carriers
      for NPs in brain tumors.

PMID- 20688392
TI  - Novel adenosine and cAMP signalling pathways in migrating glial cells.
AB  - This study was aimed at characterizing the effect of purinergic transmission on
      migration of embryonic ciliary ganglion satellite glial cells. Application of
      adenosine significantly decreased the rate of migration of glial cells whereas no
      differences were observed in the presence of ATP. The A(2B) receptor antagonist
      reverted this action, but application of an A(2A) receptor antagonist or a cAMP
      protein kinase inhibitor had no effect on the agonist's stimulation. Forskolin,
      which stimulates adenylate cyclase activity, and the cAMP analogue 8-CPT-2'-O-Me
      cAMP, which selectively activates the guanine exchange factor Epac1, mimicked the
      effect of adenosine. In addition, intracellular calcium measurements studies
      revealed that application of either adenosine or ATP induced an increase in
      [Ca(2+)]i and that the adenosine-induced [Ca(2+)]i response was due to Ca(2+)
      entry and was blocked by an A(2A) receptor antagonist, SCH 58261, or by high
      Gd(3+) concentrations. Furthermore, forskolin, but not 8-CPT-2'-O-Me-cAMP,
      activated the Ca(2+) entry which was blocked by Gd(3+) and was independent of
      cAMP-protein kinase activity. These results demonstrate the involvement of
      purinergic P1 signalling in the regulation of cellular migration, and point to
      the importance of adenosine as a negative modulator of migration of peripheral
      developing glial cells and as an activator of Ca(2+) entry.

PMID- 20688394
TI  - Effect of the nonpeptide thrombopoietin receptor agonist eltrombopag on
      megakaryopoiesis of patients with lower risk myelodysplastic syndrome.
AB  - Eltrombopag is a nonpeptidyl thrombopoietin receptor agonist. We evaluated the ex
      vivo effect of eltrombopag on megakaryopoiesis of patients with lower risk
      myelodysplastic syndromes (MDSs). At a concentration of 0.1MUg/mL, eltrombopag
      resulted in a significant increase in the number of megakaryocytic colonies in
      MDS patients and healthy controls compared to baseline. This dose of eltrombopag
      did not exert any significant change in the proliferation rate or the survival
      characteristics of patient CD34(+) cells that might clinically imply an
      unfavorable effect on patients' outcome. These encouraging preclinical data
      support the rationale of using eltrombopag in the clinic for alleviation of
      thrombocytopenia in lower risk MDS patients.

PMID- 20688393
TI  - High dose cytarabine plus gemtuzumab ozogamicin for patients with relapsed or
      refractory acute myeloid leukemia: Cancer and Leukemia Group B study 19902.
AB  - Gemtuzumab ozogamicin (GO), an anti-CD33 immunoconjugate, was combined with high
      dose cytarabine (HiDAC; cytarabine 3g/m(2) over 3h daily for 5 days) for adults
      with relapsed or refractory AML. HiDAC plus GO 9mg/m(2) on day 7 and 4.5mg/m(2)
      on day 14 was not tolerated, but HiDAC followed by GO 9mg/m(2) on day 7 was safe:
      12/37 (32%) patients with relapsed AML achieved complete remission. Median
      overall survival was 8.9 months. No grade 4 hepatic veno-occlusive disease was
      observed. This regimen merits further study, both in this setting and as a
      remission consolidation therapy.

PMID- 20688395
TI  - Relationship of serum imatinib trough level and response in CML patients: long
      term follow-up.
AB  - One hundred and three patients with Philadelphia chromosome or BCR-ABL positive
      chronic myeloid leukemia (CML) in chronic phase who were on oral imatinib were
      included in this study. The study aimed to assess the relationship between
      imatinib trough serum levels and clinical outcome (as determined by molecular
      response) in Jordanian CML patients who have been on imatinib therapy for at
      least 12 months. The mean trough imatinib serum level in the group with complete
      molecular response (CMR) was 2891+/-856 ng/ml, the group with major molecular
      response (MMR) was 2337+/-434 ng/ml, the group with complete cytogenetic response
      (CCyR) was 1817+/-563 ng/ml, and the group without CCyR was 1723+/-673 ng/ml. A
      receiver operating characteristic (ROC) curve was constructed after dividing
      patient sample into two groups, those with MMR or better and those without MMR,
      in order to estimate a threshold for imatinib level that correlates with a
      favorable response (the former group), and analysis yielded a value of 2158
      ng/ml.

PMID- 20688397
TI  - A primary objective of the 2008 workshop was to bring these scientists together
      in one location to facilitate interactions and the exchange of information.
      Preface.

PMID- 20688396
TI  - Effects of Cd- and Zn-enriched sewage sludge on soil bacterial and fungal
      communities.
AB  - The effects of sewage sludge selectively enriched with Cd and Zn, both singly and
      in combination, on the bacterial, fungal, Alphaproteobacteria and Actinobacteria
      communities of a soil under arable or grassland management were studied with a
      PCR-DGGE approach. The effects of Cd and Zn were evaluated after a short time (7
      d) when the Cd and Zn solubility were low and the C availability was high, and
      again after 180 d when the labile sludge C was mineralized and the effects of
      heavy metals predominated. In the arable soil all treatments induced significant
      short-term changes in the studied microbial groups, and long-term changes were
      observed in Actinobacteria and fungal communities. In the grassland soil, all
      treatments induced significant short-term changes in the studied microbial groups
      except for Alphaproteobacteria and fungi, and long-term effects on the
      actinobacteria and fungal communities. It was concluded that incorporation of Cd-
      and Zn-rich sludge into soils may have both short- and long-term effects on
      various bacterial phylogenetic groups whereas the metals may be better tolerated
      by the dominant soil fungi. In this study the impact was greater in arable than
      in grassland soil.

PMID- 20688398
TI  - Characterisation of Foxp3 splice variants in human CD4+ and CD8+ T cells-
      identification of Foxp3Delta7 in human regulatory T cells.
AB  - Foxp3 is proposed to play a critical role in the development and function of
      regulatory T cells. Functional and transgenic studies in mice propose Foxp3 as a
      "regulatory T cell lineage specification factor" but conflicting data exist in
      humans. Expression of multiple Foxp3 splice variants in humans represents an
      additional layer of complexity for this transcription factor and acts as a
      possible mechanism of regulating protein diversity. We report the identification
      of a novel splice variant of Foxp3, called Foxp3Delta7, in ex vivo CD4+CD25+ T
      cells and CD8+ regulatory T cell clones. Foxp3Delta7 lacks the 81bp region that
      encodes exon 7 of Foxp3, which is a part of the leucine zipper domain of the
      protein. The three splice variants of Foxp3 namely Foxp3FL, Foxp3Delta2 and
      Foxp3Delta7 are co-expressed in ex vivo human CD4+CD25+ T cells and CD8+ Treg
      clones. Stimulation of freshly isolated CD4+CD25+ T cells with anti-CD3 and anti
      CD28 antibodies leads to a 140-fold upregulation of Foxp3Delta7 within 24h of
      stimulation, which is ~10-fold greater than that observed in stimulated CD4+CD25-
      T cells. In addition, resting CD8+ Treg cells have decreased expression of
      Foxp3FL and Foxp3Delta2; however they have a 10-fold higher expression of
      Foxp3Delta7, in comparison to ex vivo CD4+CD25+ T cells. In order to assess the
      functional effects of these Foxp3 isoforms, we carried out lentivirus expression
      studies. All three isoforms were capable of inducing increased levels of CD25
      expression in primary human CD4+ T cells, along with a tendency to decreased
      levels of CD127. Further investigation into pathways that alter the relative
      proportions of Foxp3 isoforms, and hence their interaction with other
      transcriptional co-regulators, will help to define the role of Foxp3 isoforms in
      immune regulation.

PMID- 20688399
TI  - Intravaginal infection with herpes simplex virus type-2 (HSV-2) generates a
      functional effector memory T cell population that persists in the murine genital
      tract.
AB  - Although the female genital tract is the main portal of entry for sexually
      transmitted infections in women, we still have limited understanding of the
      generation, maintenance and characteristics of memory T cells in the local
      tissue. Here, we utilized a mouse model of intravaginal HSV-2 infection and
      tetramers against the immunodominant HSV glycoprotein B epitope recognized by
      CD8+ T cells to examine the generation, maintenance and characteristics of anti
      HSV memory T cells in the genital tract following acute infection. Our results
      show that the highest percentage of HSVgB-specific CD8+ T cells was found in the
      genital tract compared to the spleen or iliac lymphnode. Indeed, although the
      actual number of CD8+ T cells contracted following viral clearance, approximately
      one quarter of the CD8+ population that remained in the genital tissue was HSVgB
      specific. Memory gB-tetramer+CD8 T cells in the genital tract were positive for
      CD127 and KLRG1 and negative for CD62L and CCR7, thus confirming that HSV
      specific CD8 cells were effector memory T cells that lack the capacity for homing
      to lymphoid tissues. Functionally, both memory CD8+ and CD4+ HSV-specific
      populations in the genital tract produced IFNgamma when stimulated in vitro and
      CD4+ cells also produced TNFalpha. Genital HSVgB-specific memory T cells
      expressed tissue-homing integrins CD103 (alphaE integrin) and CD49a (VLA-1 or
      alpha1 integrin). Our findings suggest that HSV-specific memory T cells are
      retained in the genital tract, poised to act as an early line of defense against
      future virus encounter.

PMID- 20688400
TI  - Specificity of depression following an acute coronary syndrome to an adverse
      outcome extends over five years.
AB  - Many studies have demonstrated that depression is associated with a worse
      cardiovascular outcome and increased risk of death in those experiencing an acute
      coronary syndrome (ACS). Recent studies have suggested, however, that any
      association is strongly influenced by the timing of the depression, with post-ACS
      depression providing the greatest risk. Establishing any timing impact should
      assist etiological clarification. We initially recruited 489 subjects
      hospitalized for an ACS, assessed lifetime and current depression, and then - at
      1 and 12 months - assessed subsequent depression. Subjects were followed for up
      to 5 years to assess cardiovascular outcome and the impact of depression at
      differing time points, with three defined poor outcome categories (i.e. cardiac
      admission and/or cardiac rehospitalization). While outcome was associated with a
      number of non-depression variables, a poor outcome was most clearly associated
      with depressive episodes emerging at the time of the ACS but with some risk
      affected by episodes that commenced prior to the ACS and being persistent.
      Neither lifetime depressive episodes nor transient depressive episodes occurring
      around the baseline ACS event appeared to provide any risk. Study findings
      indicate that any differential deleterious impact of post-ACS depression has both
      short-term and longer-term outcomes, and, by implicating the centrality of post
      ACS depression, should assist studies seeking to identify causal explanations.

PMID- 20688401
TI  - Partial characterization and distribution of the chemokines CCL25 and CCL28 in
      the bovine system.
AB  - Chemokines have been shown to play a major role in the efficient accumulation and
      localization of leukocytes to tissues via interactions with their cognate
      receptors. The chemokine/chemokine receptor pairs CCL25/CCR9 and CCL28/CCR10 have
      been shown to play a vital role in the trafficking of antibody secreting cells to
      mucosal tissues. Although the importance of these chemokines in mediating
      effective immune responses is well described, the distribution of these molecules
      has not been previously characterized in the cow. In this report we describe the
      mRNA expression patterns of these chemokine/chemokine receptor pairs in the
      bovine system. Quantitative mRNA analysis shows that these molecules exhibit
      unique expression patterns and suggest that these chemokines play a major role in
      the accumulation of receptor bearing cells to specific mucosal tissues.

PMID- 20688402
TI  - Hearing assessment in high-risk congenital diaphragmatic hernia survivors.
AB  - OBJECTIVE: To report results of audiometric evaluations in high-risk congenital
      diaphragmatic hernia survivors and their exposure to audiological risk factors
      (mechanical ventilation, high frequency oscillation, aminoglycoside therapy and
      neuromuscular blocking agents). DESIGN: All newborns with high-risk congenital
      diaphragmatic hernia born between January 2003 and June 2009 were treated
      consecutively at the Neonatal Intensive Care Unit, Pediatric Hospital, University
      of Padova. Thirty-two survived and 26 of them underwent formal audiological
      evaluation (tonal and speech audiometry, otoacoustic emission, and immitance
      measurements) and follow up. RESULTS: Twenty-one children had normal hearing; 4
      had conductive hearing loss, which was successfully treated; and 1 had severe
      sensorineural hearing loss and suffers from Turner syndrome. CONCLUSIONS: Our
      series revealed a lower prevalence of sensorineural hearing loss in high-risk
      congenital diaphragmatic hernia survivors than in other studies, suggesting that
      the association between hearing loss and congenital diaphragmatic hernia has yet
      to be accurately defined and fully elucidated.

PMID- 20688403
TI  - Evaluation of auditory development in infants and toddlers who received cochlear
      implants under the age of 24 months with the LittlEARS) Auditory Questionnaire.
AB  - BACKGROUND AND AIMS: Newborn hearing screening and early intervention for
      congenital hearing loss have created a need for tools assessing the hearing
      development of very young children. A multidisciplinary evaluation of children's
      development is now becoming standard in clinical practice, though not many
      reliable diagnostic instruments exist. For this reason, the LittlEARS Auditory
      Questionnaire (LEAQ) was created to assess the auditory skills of a growing
      population of infants and toddlers who receive hearing instruments. The LEAQ
      relies on parent report, which has been shown to be a reliable way of assessing
      child development. Results with this tool in a group of children who received
      very early cochlear implantation are presented. METHODS: The LEAQ is the first
      module of the LittlEARS comprehensive test battery for children under the age of
      two who have normal hearing (NH), cochlear implants (CIs) or hearing aids (HAs).
      The LEAQ is a parent questionnaire comprised of 35 "yes/no" questions which can
      be completed by parents in less than 10 min. Sixty-three children who received
      unilateral CIs at a young age were assessed longitudinally and their performance
      was compared to that of a NH group. RESULTS: All CI children reached the maximum
      possible score on the LEAQ on average by 22 months of hearing age, i.e. 38 months
      of chronological age. In comparison, the NH group reached the maximum score by 24
      months of age demonstrating that auditory skills of CI children often develop
      quicker than those of NH children. In the two comparison groups of children aged
      (a) younger and older than 12 months, and (b) between 6-9 and 21-24 months at
      first fitting, the early implanted children reached the highest scores faster
      than the later implanted children. Furthermore, three children with additional
      needs were tested. They showed slower growth over time but also received benefits
      from early implantation. CONCLUSIONS: The LEAQ is a quick and effective tool for
      assessing auditory skills of very young children with or without hearing loss. In
      our study, the auditory skills of children with CI progressed very quickly after
      implantation and were comparable with those of NH peers.

PMID- 20688404
TI  - Outcome of first-ever acute ischemic stroke in the elderly.
AB  - Our purpose was to evaluate the outcome of patients aged 70 years or older with a
      first-ever acute ischemic stroke and to identify the factors which determine poor
      outcome. Data from 115 patients, non-disabled prior to stroke, consecutively
      admitted to a medical department of a teaching hospital over a 30-month period,
      were prospectively collected at stroke onset and 6-month follow-up. Clinical and
      brain imaging findings and functional status were recorded. Predictors of
      unfavorable outcome at 6 months, defined as a modified Rankin Scale score >2,
      were analyzed by multiple logistic regression. The mean age of this cohort was
      78.6 years (SD, 5.7) and 66.1% were women, 73.9% had hypertension, 25.2%
      diabetes, 36.0% atrial fibrillation (AF), 33.9% heart failure (HF), 15.8%
      previous transient ischemic attack (TIA), 47.8% a Charlson comorbidity index
      (CCI) score >1 and 52.2% a baseline National Institute of Health stroke scale
      (NIHSS) score >= 6. At 6 months, 54 patients (47%) had unfavorable outcome and
      the independent predictors of poor outcome were the initial systolic blood
      pressure and the NIHSS score on admission. In conclusion, near 50% of these old
      patients were dependent or dead 6 months after stroke onset and the main
      predictor of poor outcome was the neurological severity of stroke.

PMID- 20688405
TI  - Health, aging and childhood socio-economic conditions in Mexico.
AB  - We investigate the long-term effect of childhood socio-economic conditions on the
      health of the elderly in Mexico. We utilize a panel of individuals aged 50 and
      above from the Mexican Health and Aging Survey and find that the conditions under
      which the individual lived at the age of 10 affect health in old age, even
      accounting for education and income. This paper contributes to the literature of
      the long-term effects of childhood socio-economic status by being the first, to
      our knowledge, to consider exclusively the case of the elderly in a developing
      country.

PMID- 20688406
TI  - Removal of Salmonella Enteritidis from commercial unpasteurized liquid egg white
      using pilot scale cross flow tangential microfiltration.
AB  - Effectiveness of a cross flow microfiltration (MF) process for removal of a
      cocktail of Salmonella enterica serovar Enteritidis species from commercial
      unpasteurized liquid egg white (LEW) from a local egg breaking plant, while
      maintaining its functional properties was evaluated. To facilitate MF, LEW was
      wedge screened, homogenized and then diluted (1:2 w/w) with distilled water
      containing 0.5% sodium chloride. Diluted unpasteurized LEW was inoculated with
      five strains of S. Enteritidis (ATCC 4931, ATCC BAA-708, ATCC 49215, ATCC 49218,
      and ATCC BAA-1045) to a level of approximately 10(7)CFU/mL of LEW and
      microfiltered using a ceramic membrane. Process parameters influencing egg white
      functional properties and pathogen removal efficiency were evaluated. Average
      permeates flux increased by almost 126% when pH of LEW was adjusted from pH 8 to
      pH 7 at 25 degrees C. Microbial removal efficiency was at least, on average,
      6.8Log(10)CFU/mL (limit of detection < or =0.5Log(10)CFU/mL). Functional property
      analysis indicated that the MF process did not alter the foaming power of LEW.

PMID- 20688407
TI  - Detection and differentiation of Vibrio spp. in seafood and fish samples with
      cultural and molecular methods.
AB  - Vibrio spp. as natural inhabitants of sea- and brackwater of both tropical and
      temperate regions of the world are commonly found in different kinds of seafood.
      Even among the three main human pathogenic species Vibrio parahaemolyticus,
      Vibrio cholerae and Vibrio vulnificus most of the isolates from seafood do not
      carry the different virulence factors responsible for foodborne infections.
      Therefore, the risk assessment of Vibrio spp. in seafood is currently based
      mainly on the knowledge of the genetic setting of foodborne strains. For the
      detection and differentiation of Vibrio spp. (V. parahaemolyticus, V. cholerae
      and V. vulnificus) three probe-based multiplex real-time PCR systems were
      developed and validated. One real-time PCR system simultaneously detects V.
      parahaemolyticus, V. cholerae and V. vulnificus on genus level combined with an
      Internal Amplification Control. The detection limit for the system was between
      1cfu/mL and 10cfu/mL in pure culture and in different artificially contaminated
      sample material, e. g. prawns or Alaska Pollock. The other two PCR systems were
      implemented for the detection of different virulence genes of V. parahaemolyticus
      and V. cholerae isolates. The molecular detection systems were applied for the
      investigation of 338 raw and cooked seafood and fish samples for the presence of
      the different Vibrio spp. The collected data indicate that the PCR systems can be
      useful for rapid detection and differentiation of Vibrio spp. in different food
      matrices as basis for a preventive consumer protection policy.

PMID- 20688408
TI  - Water activity and temperature effects on mycotoxin production by Alternaria
      alternata on a synthetic tomato medium.
AB  - Alternaria spp. have been reported to be the most frequent fungal species
      invading tomatoes. Certain species, in particular the most common one, A.
      alternata, are capable of producing several mycotoxins in infected plants and in
      agricultural commodities. Alternariol (AOH), alternariol monomethyl ether (AME),
      and tenuazonic acid (TA) are some of the main Alternaria mycotoxins that can be
      found as contaminants of food. The objective of this study was to determine the
      effect of water activity (a(w), 0.904, 0.922, 0.954, and 0.982) and temperature
      (6, 15, 21 and 35 degrees C) on mycotoxin production on a synthetic tomato medium
      of a cocktail inoculum of five strains of A. alternata isolated from tomato
      fruits affected by Blackmould. The optimum AOH production occurred at 0.954 a(w)
      after 28days of incubation at 21 degrees C. A temperature of 21 degrees C was the
      most favourable for AOH synthesis at all a(w) levels. The maximum concentration
      of AME was determined at 0.954 a(w) and 35 degrees C. The optimum conditions for
      TA accumulation were 0.982 a(w) and 21 degrees C. At the 0.904 a(w) no growth or
      germination was registered at 6 degrees C and 15 degrees C over the whole
      incubation period. At 21 degrees C and 35 degrees C growth occurred slowly but
      none of the toxins were detected at this a(w) level. In general, high a(w) levels
      were favourable for mycotoxin production. None of the other toxins was detected
      at quantifiable levels at 6 degrees C after the whole incubation period. A
      storage temperature of 6 degrees C or below could be considered as safe for
      tomato fruits and high moisture tomato products (a(w)>0.95), in relation with
      Alternaria toxins. The results obtained here could be extrapolated to evaluate
      the risk of spoilage in tomato fruits and tomato products caused by this
      pathogen.

PMID- 20688409
TI  - DNA microarray for tracing Salmonella in the feed chain.
AB  - In the present study we investigated if the microarray platforms Premi(r)Test
      Salmonella (PTS) and Salmonella array (SA) could be applied for the
      identification and typing of Salmonella in artificially contaminated animal feed
      materials. The results were compared to the culture-based MSRV method and
      serotyping according to Kauffman-White. The SA platform showed a specificity of
      100% for the identification of Salmonella compared to 93% with the PTS platform
      and a sensitivity of 99% or 100%, respectively. Among all identified Salmonella
      serotypes, 56% with the SA platform and 81% with the PTS platform were correctly
      identified. The difference in probe signal intensity for each probe was higher
      between duplicates analyzed with the SA platform than with the PTS platform.
      Attempts to use the microarray platforms from BPW resulted in many false negative
      samples and incorrect typing results. The microarray platforms tested were simple
      to use and might have a potential in tracing studies for Salmonella in the feed
      chain particularly when rapid information about serotypes are important.

PMID- 20688410
TI  - Comparisons of water activity and temperature impacts on growth of Fusarium
      langsethiae strains from northern Europe on oat-based media.
AB  - This study has examined the effect of water activity (a(w), 0.995-0.90) and
      temperature (10-37 degrees C) on the lag phases prior to growth, growth rates and
      used models to develop two dimensional profiles for optimum and marginal
      conditions for two strains of Fusarium langsethiae from four northern European
      countries (UK, Norway, Sweden, and Finland) on an oat-based medium. Results
      showed that the optimum a(w) for growth was at 0.98-0.995 and 25 degrees C. The
      limit for growth of the strains was at 0.92-0.93 a(w) with minima of 10 degrees
      C. No growth occurred at 37 degrees C. The lag phases prior to growth were lowest
      under optimum conditions and extended to >10days at marginal conditions.
      Statistical analyses of intra and inter-strain differences in terms of both lag
      phases prior to growth and growth rates were not statistically significant.
      However, a(w) and temperature were statistically significant factors. Two
      dimensional profiles for strains from each country of origin were built to
      identify optimum and marginal conditions for F. langsethiae for the first time.
      These environmental profiles will be beneficial for improving the ecological
      knowledge of this species which is able to produce trichothecene mycotoxins in a
      range of temperate cereals.

PMID- 20688411
TI  - Microorganisms associated with Maari, a Baobab seed fermented product.
AB  - A microbiological study was carried out on Baobab fermented seeds (Maari)
      obtained from 4 different production sites in Burkina Faso (Mansila, Toulfe,
      Ouagadougou and Gorgadji). A total of 390 representative isolates comprising 251
      aerobic mesophilic bacteria (AMB) and 139 lactic acid bacteria (LAB) were
      isolated and identified to species level using a combination of pheno- and
      genotypic methods including conventional morphological analysis, carbohydrate
      fermentation profiling, rep-PCR ((GTG)(5)-fingerprinting) and 16S rRNA gene
      sequencing. The fermentation of Baobab seeds was initiated by the AMB identified
      as Bacillus subtilis (82% of AMB isolates) and Staphylococcus sciuri (18% of AMB
      isolates). No lactic acid bacteria were isolated at the beginning of the process.
      After 24h fermentation time, Enterococcus faecium appeared in the fermenting
      seeds and remained until the end of the fermentation, as the predominant LAB. In
      Maari collected from retail outlets the AMB count ranged from 6.7log10CFU/g to
      10log10CFU/g while the LAB load ranged from 4.4log10CFU/g to 9.9log10CFU/g. The
      AMB were identified as belonging to genus Bacillus (12 species), Staphylococcus
      (3 species) and one species of Aerococcus, Macrococcus, Leifsonia, Kurthia,
      Proteus, Acinetobacter and Globicatella, respectively. A putatively novel,
      previously undescribed Corynebacterium sp. was also found. E. faecium was the
      dominant LAB in all investigated retail samples except one sample dominated by
      Pediococcus acidilactici.

PMID- 20688412
TI  - Increased degranulation of natural killer cells during acute HCV correlates with
      the magnitude of virus-specific T cell responses.
AB  - BACKGROUND & AIMS: Natural killer (NK) cells provide early defense against viral
      infections by killing infected cells and producing cytokines that inhibit viral
      replication. NK cells also interact with dendritic cells (DCs) and this
      reciprocal interaction regulates both innate and adaptive immunity. Genetic
      studies have suggested that NK cell activity is a determinant of HCV infectious
      outcome but a functional correlation has not been established. We hypothesized
      that increased NK cell activity during acute HCV infection correlates with
      spontaneous viral clearance. METHODS: We used multiparametric flow cytometry to
      monitor longitudinally the phenotype and the activity of NK cells in a cohort of
      intravenous drug users following HCV exposure. Three groups were studied: acute
      HCV with chronic evolution (n = 13), acute resolving HCV (n = 11), and exposed un
      infected individuals (n = 10). We examined the expression of several NK cell
      activating and -inhibiting receptors, IFN-gamma production and CD107a
      degranulation upon stimulation, and the kinetics of NK cell responses relative to
      T cell responses. RESULTS: We observed decreased expression of the inhibitory
      NKG2A receptor in NK cells following spontaneous HCV clearance. In addition, we
      observed increased NK cell degranulation during acute HCV irrespective of
      infectious outcome. NK cell peak responses preceded or coincided with peak T cell
      responses. Furthermore, NK cell degranulation correlated with the magnitude of
      HCV-specific T cells. CONCLUSIONS: Our results demonstrate that NK cells are
      activated during acute HCV regardless of infection outcome and may play an
      indirect role through induction and priming of T cell responses.

PMID- 20688413
TI  - Lung cancer in England: information from the National Lung Cancer Audit (LUCADA).
AB  - AIMS: Our aims were to determine whether the information in the National Lung
      Cancer Audit database (LUCADA) is influenced by the completeness of reporting and
      to describe the current socio-demographics and survival of people with lung
      cancer in England. METHODS: Using national registry data as a gold standard we
      stratified NHS Trusts into quartiles on the basis of their patient ascertainment.
      We assessed the distribution of patient features across these quartiles using Cox
      and logistic regression. We then examined overall survival and access to
      treatment. RESULTS: We analysed data for 60,059 patients whose data were entered
      between 2004 and 2008. There was little variation in key patient features,
      treatment and median survival across quartiles of data completeness. Socio
      economic disadvantage did not influence survival or access to surgery but was
      related to a decreased use of chemotherapy. CONCLUSION: Our findings suggest that
      LUCADA accurately describes people in England who are diagnosed with lung cancer
      and can therefore be used to drive health care improvements. Individual patient
      socio-economic status does not affect survival and has only a limited impact on
      access to treatment and so NHS Trust level factors should be studied to explain
      the previously published regional variations in these outcomes.

PMID- 20688414
TI  - Compromising genetic diversity in the wild: unmonitored large-scale release of
      plants and animals.
AB  - Large-scale exploitation of wild animals and plants through fishing, hunting and
      logging often depends on augmentation through releases of translocated or
      captively raised individuals. Such releases are performed worldwide in vast
      numbers. Augmentation can be demographically and economically beneficial but can
      also cause four types of adverse genetic change to wild populations: (1) loss of
      genetic variation, (2) loss of adaptations, (3) change of population composition,
      and (4) change of population structure. While adverse genetic impacts are
      recognized and documented in fisheries, little effort is devoted to actually
      monitoring them. In forestry and wildlife management, genetic risks associated
      with releases are largely neglected. We outline key features of programs to
      effectively monitor consequences of such releases on natural populations.

PMID- 20688415
TI  - Antigen-specific regulatory T cells are detected in Peyer's patches after the
      interaction between T cells and dendritic cells loaded with orally administered
      antigen.
AB  - Systemic immune tolerance is induced for orally administered antigen, and this
      phenomenon is called oral tolerance. However, the mechanism of oral tolerance has
      not been completely elucidated. It has been suggested that antigen presentation
      and generation of regulatory T cells in Peyer's patches (PPs) are important for
      induction of oral tolerance. Hence, we orally administered fluorescence-labelled
      antigen to mice and examined kinetics of the antigen and interaction between
      antigen-loaded dendritic cells and T cells. It was visualized that dendritic
      cells in PP rapidly take up antigen. We next transferred antigen-specific naive T
      cells from T cell receptor transgenic mice and administered the antigen orally.
      Antigen-specific T cells accumulated in IFR in PP and DCs that have ingested
      antigen come in contact with antigen-specific T cells in IFR. The accumulated T
      cells were then collected and analyzed for the pattern of gene expression by real
      time PCR, which revealed a gene expression pattern similar to that of FoxP3
      positive regulatory T (T(reg)) cells. CCR9, an intestinal homing marker, was also
      strongly expressed. These results suggest that DCs that have captured oral
      antigens in PPs locally induce antigen-specific naive T cells to differentiate
      into T(reg) cells with the intestinal homing phenotype.

PMID- 20688416
TI  - The complex interactions between host immunity and non-biotrophic fungal
      pathogens of wheat leaves.
AB  - Significant progress has been made in elucidating the mechanisms used by plants
      to recognize pathogens and activate "immune" responses. A "first line" of defense
      can be triggered through recognition of conserved Pathogen or Microbe Associated
      Molecular Patterns (PAMPs or MAMPs), resulting in activation of basal (or non
      host) plant defenses, referred to as PAMP-triggered immunity (PTI). Disease
      resistance responses can also subsequently be triggered via gene-for-gene type
      interactions between pathogen avirulence effector genes and plant disease
      resistance genes (Avr-R), giving rise to effector triggered immunity (ETI). The
      majority of the conceptual advances in understanding these systems have been made
      using model systems, such as Arabidopsis, tobacco, or tomato in combination with
      biotrophic pathogens that colonize living plant tissues. In contrast, how these
      disease resistance mechanisms interact with non-biotrophic (hemibiotrophic or
      necrotrophic) fungal pathogens that thrive on dying host tissue during successful
      infection, is less clear. Several lines of recent evidence have begun to suggest
      that these organisms may actually exploit components of plant immunity in order
      to infect, successfully colonize and reproduce within host tissues. One
      underlying mechanism for this strategy has been proposed, which has been referred
      to as effector triggered susceptibility (ETS). This review aims to highlight the
      complexity of interactions between plant recognition and defense activation
      towards non-biotrophic pathogens, with particular emphasis on three important
      fungal diseases of wheat (Triticum aestivum) leaves.

PMID- 20688418
TI  - An interactive approach to reducing blood culture contamination.

PMID- 20688417
TI  - Improved UV-B screening capacity does not prevent negative effects of ambient UV
      irradiance on PSII performance in High Arctic plants. Results from a six year UV
      exclusion study.
AB  - Long-term responses of ambient solar ultraviolet (UV) radiation were investigated
      on Salix arctica and Vaccinium uliginosum in a High Arctic heath ecosystem in
      Zackenberg, northeast Greenland. Over a period of six years, UV exclusion was
      conducted in the growing season by means of filters: 60% UV-B reduction, 90% UV
      B+UV-A reduction, UV transparent filter control, and an open control without
      filter. Plant responses were evaluated using specific leaf area, leaf content of
      UV-B absorbing compounds and PSII performance parameters derived from chlorophyll
      a fluorescence induction curves. Based on the JIP-test, we calculated the total
      performance index PI(total), which includes the integrating antennae, the PSII
      reaction center, intersystem electron transport and reduction of PSI end
      acceptors-dependent parameters. In both species, UV exclusion significantly
      decreased the content of UV-B-absorbing compounds. Salix increased its specific
      leaf area, while Vaccinium decreased it. UV exclusion increased the PI(total) in
      both species during all six years of experimentation. This response was governed
      by a significantly decreased RC/ABS, a marginally non-significant increased
      ET(o)/TR(o) and a significantly increased TR(o)/ABS=F(V)/F(M) and RE(o)/ET(o).
      These results demonstrate the current level of ambient UV-B to decrease PSII
      performance significantly in these High Arctic plants. It appears that the two
      plant species both have improved their UV-screening capacity, but through
      different strategies, although this did not sufficiently prevent negative effects
      of the ambient UV radiation. We argue the decreased PSII performance to be part
      of a response decreasing plant carbon uptake. We speculate the negative effects
      on PSII performance mediated by ambient UV irradiance to be present in years
      where warming induces early snowmelt, exposing the vegetation to high spring UV
      B, and to be present in the future to the degree the ozone layer is not fully
      recovered.

PMID- 20688419
TI  - Corynebacterium striatum as an emerging pathogen.

PMID- 20688420
TI  - Dynamic changes in PET amyloid and FDG imaging at different stages of Alzheimer's
      disease.
AB  - In this study 5 patients with mild cognitive impairment (MCI) and 9 Alzheimer's
      disease (AD) patients underwent respectively 3- and 5-year follow-up positron
      emission tomography (PET) studies with N-methyl [(11)C] 2-(4-methylaminophenyl)-6
      hydroxy-benzothiazole ((11)C-PIB) and (18)F-fluorodeoxyglucose ((18)F-FDG) to
      understand the time courses in AD disease processes. Significant increase in PIB
      retention as well as decrease in regional cerebral metabolic rate of glucose
      (rCMRglc) was observed at group level in the MCI patients while no significant
      change was observed in cognitive function. At group level the AD patients showed
      unchanged high PIB retention at 5-year follow-up compared with baseline. At the
      individual level, increased, stable, and decreased PIB retention were observed
      while disease progression was reflected in significant decrease in rCMRglc and
      cognition. In conclusion, after a long-term follow-up with PET, we observed an
      increase in fibrillar amyloid load in MCI patients followed by more stable level
      in clinical AD patients. The rCMRglc starts to decline in MCI patients and became
      more pronounced in clinical stage which related to continuous decline in
      cognition.

PMID- 20688421
TI  - [Gastric schwannoma].

PMID- 20688422
TI  - Hemispheric asymmetries in auditory distraction.
AB  - Serial-verbal short-term memory is impaired by irrelevant sound, particularly
      when the sound changes acoustically (the changing-state effect). In contrast,
      short-term recall of semantic information is impaired only by the semanticity of
      irrelevant speech, particularly when it is semantically related to the target
      memory items (the between-sequence semantic similarity effect). Previous research
      indicates that the changing-state effect is larger when the sound is presented to
      the left ear in comparison to the right ear, the left ear disadvantage. In this
      paper, we report a novel finding whereby the between-sequence semantic similarity
      effect is larger when the irrelevant speech is presented to the right ear in
      comparison to the left ear, but this right ear disadvantage is found only when
      meaning is the basis of recall (Experiments 1 and 3), not when order is the basis
      of recall (Experiment 2). Our results complement previous research on hemispheric
      asymmetry effects in cross-modal auditory distraction by demonstrating a role for
      the left hemisphere in semantic auditory distraction.

PMID- 20688423
TI  - Antepartum and postpartum maternal plasma levels of E-selectin in pre-eclampsia,
      gestational proteinuria and gestational hypertension.

PMID- 20688425
TI  - Favourable pregnancy outcome in a pregnant woman with partial hypoplasia of
      inferior vena cava and homozygous for methylenetetrahydrofolate reductase
      mutation.

PMID- 20688424
TI  - Clinical practice guidelines on menorrhagia: management of abnormal uterine
      bleeding before menopause.
AB  - BACKGROUND: Normal menstrual periods last 3-6 days and involve blood loss of up
      to 80ml. Menorrhagia is defined as menstrual periods lasting more than 7 days
      and/or involving blood loss greater than 80ml. The prevalence of abnormal uterine
      bleeding (AUB) is estimated at 11-13% in the general population and increases
      with age, reaching 24% in those aged 36-40 years. INVESTIGATION: A blood count
      for red cells+platelets to test for anemia is recommended on a first-line basis
      for women consulting for AUB whose history and/or bleeding score justify it. A
      pregnancy test by an hCG assay should be ordered. A speculum examination and Pap
      smear, according to the French High Health Authority guidelines should be
      performed early on to rule out any cervical disease. Pelvic ultrasound, both
      abdominal (suprapubic) and transvaginal, is recommended as a first-line procedure
      for the etiological diagnosis of AUB. Hysteroscopy or hysterosonography can be
      suggested as a second-line procedure. MRI is not recommended as a first-line
      procedure. TREATMENT: In idiopathic AUB, the first-line treatment is medical,
      with efficacy ranked as follows: levonorgestrel IUD, tranexamic acid, oral
      contraceptives, either estrogens and progestins or synthetic progestins only, 21
      days a month, or NSAIDs. When hormone treatment is contraindicated or immediate
      pregnancy is desired, tranexamic acid is indicated. Iron must be included for
      patients with iron-deficiency anemia. For women who do not wish to become
      pregnant in the future and who have idiopathic AUB, the long-term efficacy of
      conservative surgical treatment is greater than that of oral medical treatment.
      Placement of a levonorgestrel IUD (or administration of tranexamic acid by
      default) is recommended for women with idiopathic AUB. If this fails, a
      conservative surgical technique must be proposed; the choices include second
      generation endometrial ablation techniques (thermal balloon, microwave,
      radiofrequency), or, if necessary, first-generation techniques (endometrectomy,
      roller-ball). A first-line hysterectomy is not recommended in this context.
      Should a hysterectomy be selected for functional bleeding, it should be performed
      by the vaginal or laparoscopic routes.

PMID- 20688426
TI  - The role of tryptophan in staphylococcal nuclease stability.
AB  - Staphylococcal nuclease (SNase) has a single Trp residue at position 140.
      Circular dichroism, intrinsic and ANS-binding fluorescence, chemical titrations
      and enzymatic assays were used to measure the changes of its structure, stability
      and activities as the Trp was mutated or replaced to other positions. The results
      show that W140 is critical to SNase structure, stability, and function. Mutants
      such as W140A, F61W/W140A, and Y93W/W140A have unfolding, corrupted secondary and
      tertiary structures, diminished structural stability and attenuated catalytic
      activity as compared to the wild type. The deleterious effects of W140
      substitution cannot be compensated by concurrent changes at topographical
      locations of position 61 or 93. Local hydrophobicity defined as a sum of
      hydrophobicity around a given residue within a distance is found to be a relevant
      property to SNase folding and stability.

PMID- 20688427
TI  - Determination of effects of turbulence flow in a cathode environment on
      electricity generation using a tidal mud-based cylindrical-type sediment
      microbial fuel cell.
AB  - We examined the possibility of harvesting electricity from the surface of a tidal
      mud flat using a cylindrical-type sediment microbial fuel cell (SMFC), a marine
      mud battery (MMB), which can be applied in a sea environment where the ebb and
      flow occur due to tidal difference. In addition, we indirectly investigated the
      influence of ebb and flow in a lab, using aeration, argon gassing, and by
      agitating the cathodic solution. The MMBs consisted of cylindrical acrylic
      compartments containing a nylon membrane, an anode, and a cathode in a single
      body. The MMBs were stuck vertically into an artificial tidal mud flat such that
      the anode electrode was in direct contact with the tidal mud surface. As a
      result, the maximum current and power density generated were 35 mA/m(2) and 9
      mW/m(2), respectively, thus verifying that it is possible to harvest electricity
      from the surface of a tidal mud flat using an MMB without burying the anode
      electrode in the tidal mud. Furthermore, the results of tests using an artificial
      turbulence flow showed the flow induced by the tidal ebb and flow could allow the
      performance of MMBs to be enhanced.

PMID- 20688428
TI  - Bacteriophage hyaluronidase effectively inhibits growth, migration and invasion
      by disrupting hyaluronan-mediated Erk1/2 activation and RhoA expression in human
      breast carcinoma cells.
AB  - Aberrant hyaluronan production has been implicated in many types of tumor. In
      this context, hyaluronidase has been explored as a viable therapeutic approach to
      reduce tumoral hyaluronan. However, elevated levels of hyaluronan in tumors are
      often associated with high expression levels of cellular hyaluronidases, which
      consequently produce various sizes of saturated hyaluronan fragments with
      divergent pro-tumoral activities. The current study shows that different
      hyaluronan metabolisms of mammalian and microbial hyaluronidases could elicit
      distinct alterations in cancer cell behavior. Unlike saturated hyaluronan
      metabolites, unsaturated hyaluronan oligosaccharides produced by bacteriophage
      hyaluronidase, HylP, had no biological effect on growth of breast carcinoma
      cells. More importantly, HylP's metabolic process of hyaluronan into non
      detrimental oligosaccharides significantly decreased breast cancer cell
      proliferation, migration and invasion by disrupting Erk1/2 activation and RhoA
      expression. Our results suggest that it may be possible to exploit HylP's unique
      enzymatic activity in suppressing hyaluronan-mediated tumor growth and
      progression.

PMID- 20688429
TI  - The effect of carbon type on arsenic and trichloroethylene removal capabilities
      of iron (hydr)oxide nanoparticle-impregnated granulated activated carbons.
AB  - This study investigates the impact of the type of virgin granular activated
      carbon (GAC) media used to synthesize iron (hydr)oxide nanoparticle-impregnated
      granular activated carbon (Fe-GAC) on its properties and its ability to remove
      arsenate and organic trichloroethylene (TCE) from water. Two Fe-GAC media were
      synthesized via a permanganate/ferrous ion synthesis method using bituminous and
      lignite-based virgin GAC. Data obtained from an array of characterization
      techniques (pore size distribution, surface charge, etc.) in correlation with
      batch equilibrium tests, and continuous flow modeling suggested that GAC type and
      pore size distribution control the iron (nanoparticle) contents, Fe-GAC synthesis
      mechanisms, and contaminant removal performances. Pore surface diffusion model
      calculations predicted that lignite Fe-GAC could remove ~6.3 L g(-1) dry media
      and ~4 L g(-1) dry media of water contaminated with 30 MUg L(-1) TCE and arsenic,
      respectively. In contrast, the bituminous Fe-GAC could remove only ~0.2 L/g dry
      media for TCE and ~2.8 L/g dry media for As of the same contaminated water. The
      results show that arsenic removal capability is increased while TCE removal is
      decreased as a result of Fe nanoparticle impregnation. This tradeoff is related
      to several factors, of which changes in surface properties and pore size
      distributions appeared to be the most dominant.

PMID- 20688430
TI  - Ecofriendly synthesis and solar photocatalytic activity of S-doped ZnO.
AB  - The S-doped ZnO was prepared by new ecofriendly method, which involves simple
      mechanochemical synthesis followed by thermal decomposition of bisthiourea zinc
      oxalate (BTZO) powders. The BTZO was characterized by FTIR and TG-DTA analysis
      while S-doped ZnO crystallite was characterized by XRD, XPS, SEM, EDXS, and
      photoluminescence (PL) spectra. X-ray diffraction data suggest the single phase
      wurtzite structure for S-doped ZnO and the incorporation of sulfur expand the
      lattice constants of ZnO. Room temperature PL spectra show more number of oxygen
      vacancies in S-doped ZnO as compare to that of pure ZnO. Photocatalytic activity
      of S-doped ZnO was checked by means of solar photocatalytic degradation (PCD) of
      resorcinol, using a batch photoreactor. The PCD efficiency of S-doped ZnO was
      found to be 2 times greater than that of pure ZnO. The inherent relationship
      between PL intensity and photocatalytic activity of S-doped ZnO was discussed.

PMID- 20688431
TI  - Synthesis and characterization of hydrophobic zeolite for the treatment of
      hydrocarbon contaminated ground water.
AB  - Hydrophobic zeolite was synthesized, modified and characterized for its
      suitability as a permeable reactive barrier (PRB) material for treatment of
      hydrocarbons in groundwater. Batch sorption tests were performed along with a
      number of standard characterization techniques. High and low ionic strength and
      pH tests were also conducted to determine their impact on hydrocarbon uptake.
      Further ion exchange tests were conducted to determine the potential for the
      zeolite to act as both a hydrocarbon capture material and nutrient a delivery
      system for bioremediation. The zeolite was coated with octadecyltrichlorosilane
      (C18) to change its surface properties. The results of the surface
      characterization tests showed that the underlying zeolite structure was largely
      unaffected by the coating. TGA measurements showed a reactive carbon content of 1
      2%. Hydrocarbon (o-xylene and naphthalene) sorption isotherms results compared
      well with the behaviour of similar materials investigated by other researchers.
      Ionic strength and pH had little effect on hydrocarbon sorption and the treated
      zeolite had an ion exchange capacity of 0.3 mequiv./g, indicating it could be
      utilised as a nutrient source in PRBs. Recycle tests indicated that the zeolite
      could be used cleaned and reused at least three times without significant
      reduction in treatment effectiveness.

PMID- 20688432
TI  - Frictional properties of single crystals HMX, RDX and PETN explosives.
AB  - The frictional properties of single crystals of cyclotetramethylene
      tetranitramine (HMX), cyclotrimethylene trinitramine (RDX) and pentaerythritol
      tetranitrate (PETN) secondary explosives are examined using a sensitive friction
      machine. The explosive crystals used for the measurements are at least 3.5 mm
      wide. The friction coefficients between crystals of the same explosive (i.e., HMX
      on HMX, etc.), crystals of different explosives (i.e., HMX on RDX, etc.), and
      each explosive and a well-polished gauge steel surface are determined. The
      frictional surfaces are also studied under an environmental scanning electron
      microscope (ESEM) to analyze surface microstructural changes under increasing
      loading forces. The friction coefficients vary considerably with increasing
      normal loading forces and are particularly sensitive to slider shapes, crystal
      roughness and the mechanical properties of both the slider and the sample. With
      increasing loading forces, most friction experiments show surface damage,
      consisting of grooves, debris, and nano-particles, on both the slider and sample.
      In some cases, a strong evidence of a localized molten state is found in the
      central region of the friction track. Possible mechanisms that affect the
      friction coefficient are discussed based on microscopic observations.

PMID- 20688433
TI  - Changes in expression of NMDA-NR1 receptor subunits in the rostral ventromedial
      medulla modulate pain behaviors.
AB  - NMDA receptors have an important role in pain facilitation in rostral
      ventromedial medulla (RVM) and the NR1 subunit is essential for its function.
      Studies suggest that the NMDA receptors in RVM are critical to modulate both
      cutaneous and muscle hypersensitivity induced by repeated intramuscular acid
      injections. We propose that increased expression of the NR1 subunit in the RVM is
      critical for the full development of hypersensitivity. To test this we used
      recombinant lentiviruses to over-express the NR1 subunit in the RVM and measured
      nociceptive sensitivity to cutaneous and muscle stimuli. We also downregulated
      the expression of NR1 in the RVM and measured the hyperalgesia produced by
      repeated-acid injections. Increasing the expression of NR1 in the RVM reduces
      cutaneous and muscle withdrawal threshold, and decreasing the expression of NR1
      in the RVM increases the muscle withdrawal threshold and prevents the development
      of hyperalgesia in an animal model of muscle pain. These results suggest that the
      NR1 subunits in the RVM are critical for modulating NMDA receptor function, which
      in turn sets the 'tone' of the nervous system's response to noxious stimuli and
      tissue injury.

PMID- 20688434
TI  - Diagnoses of fipronil resistance in Brazilian cattle ticks (Rhipicephalus
      (Boophilus) microplus) using in vitro larval bioassays.
AB  - Fipronil is a phenylpyrazolic insecticide that is widely used in agriculture and
      has been recently used to control the cattle tick, Rhipicephalus (Boophilus)
      microplus. Because of the serious problems associated with resistance to the
      available acaricides, this product has been used as an important alternative to
      control acaricide-resistant ticks. The objective of this work was to analyse the
      fipronil sensitivity of ticks that were collected from farms with a history of
      fipronil use by larval bioassays. A total of 11 Brazilian tick populations were
      studied: one population from Rio Grande do Sul, one population from Mato Grosso
      do Sul and nine populations from Sao Paulo. To validate the assays, susceptible
      reference strains, POA (Porto Alegre, Brazil) and Mozo (Dilave, Uruguay), and
      ticks from six different farms that never used fipronil were tested. The
      resistance of various tick populations to technical grade fipronil (95.3%) was
      primarily evaluated using the larvae immersion test (LIT) and the larval packet
      test (LPT), when a sufficient number of larvae was collected. Using the LIT, the
      resistance ratios (RR(50)) of the tick populations from Rio Grande do Sul and
      Mato Grosso do Sul were 14.9 and 2.6, respectively, and the populations derived
      from Sao Paulo had RR(50)s ranging from 2.5 to 6.9. Four populations were
      evaluated with the LPT, and two populations displayed lower RR(50), while other
      populations displayed higher RR(50) than those determined by the LIT. This
      article reports the first cases of fipronil resistance in Brazil and highlights
      the LIT as a more sensitive technique for the evaluation of fipronil resistance
      in R. (B) microplus ticks. We suggest the use of the LIT as an evaluation tool
      for monitoring fipronil resistance in the control programmes of R. (B) microplus.

PMID- 20688435
TI  - Epidemiology and risk factors for exposure to gastrointestinal nematodes in dairy
      herds in northwestern Europe.
AB  - In this survey, the epidemiology of gastrointestinal (GI) nematodes in dairy
      herds in five northwestern European countries was studied using a standardized
      Ostertagia ostertagi ELISA applied on bulk-tank milk, and a common questionnaire.
      The levels of exposure to GI nematodes were high in Belgium, the UK and Ireland,
      intermediate in Germany and low in Sweden, with a mean (95% confidence interval)
      ELISA result (ODR) of 0.83 (0.82-0.84) in Belgium, 0.82 (0.79-0.84) in the UK and
      0.80 (0.78-0.83) in Ireland; significantly higher than the mean ODR of 0.66 (0.65
      0.68) in Germany and 0.52 (0.51-0.53) in Sweden. Taking into account previous
      literature, these regional differences are likely to be systematic. Regional
      variations in exposure were significantly explained by differences in management
      (grazing time per day, mowing, the months of turnout, housing and anthelmintic
      treatment). However, after controlling for these factors, significant regional
      differences in levels of exposure remained, suggesting an importance for climate
      (temperature, rainfall) and unmeasured management factors. This study emphasizes
      that GI nematode-induced production losses should be considered on a large
      percentage of northwest European dairy herds. Proposals are made for the
      development of region-specific monitoring and control strategies. Further
      advances in this area are likely to come from intervention studies that
      investigate the feasibility of control measures and from studies on the potential
      effects of climatic conditions on shifts in levels of exposure between years and
      regions.

PMID- 20688436
TI  - Retrospective analysis of photographic evaluation of burn depth.
AB  - PURPOSE OF THE STUDY: Evaluation of burn depth is an essential and difficult step
      that conditions surgical or non-surgical treatment. The purpose of the study is
      to evaluate the opportunity to diagnose burn depth only with initial photography
      of the burn. METHOD: For all patients admitted to our burn unit between January
      2002 and March 2008, we performed a retrospective analysis of burn depth based on
      a photographic evaluation. Blinded photos were submitted to three experienced
      surgeons who were asked if the burns required a graft or not. The diagnosis done
      by photography evaluation was then compared to initial diagnosis and treatment.
      MAIN FINDINGS: Out of 911 patients photography analysed, the photographic
      evaluation was equivalent to clinical evaluation in 76% of the cases. The
      sensitivity and specificity of the photographic evaluation were, respectively,
      0.77 and 0.75. The main evaluation errors were in intermediate burns (29.6% of
      errors) and were more often due to overestimation of the depth. In 75% of cases,
      there was a full agreement between 3 surgeons (683/911). A secondary analysis
      excluding electrical and chemical injuries showed an improvement of
      predictability. CONCLUSION: Even though a photographic analysis cannot replace
      clinical examination, photographic evaluation may be one option to consider for
      an early distance diagnosis.

PMID- 20688437
TI  - Oxytocin indexes relational distress following interpersonal harms in women.
AB  - The hypothalamic neuropeptide oxytocin, known for its involvement in social
      affiliation and bonding in animals, has recently been associated with a host of
      prosocial behaviors that are beneficial for maintaining positive social
      relationships in humans. Paradoxically, however, people with high endogenous
      levels of oxytocin also tend to report relational distress and interpersonal
      difficulties in their everyday lives. To address these contradictory findings,
      oxytocin reactivity was measured in response to a well-defined laboratory task in
      young adult women following recent interpersonal harms. Elevated mean peripheral
      oxytocin reactivity (but not baseline levels of oxytocin or cortisol reactivity)
      was associated with increased post-conflict anxiety and decreased levels of
      forgiveness. These results corroborate previous research implicating oxytocin as
      a neuroendocrine marker of relational distress, but not general stress, and
      demonstrate the utility of studying oxytocin in response to naturally occurring
      relational events.

PMID- 20688438
TI  - Cortisol reactivity to social stress in adolescents: role of depression severity
      and child maltreatment.
AB  - This study examined the hypothesis that depressed adolescents with a history of
      childhood maltreatment will show greater cortisol reactivity to psychological
      stress challenge than those without, and this relation will be moderated by level
      of depression severity. Seventy-one adolescents were exposed to the Trier Social
      Stress Test. Salivary cortisol was assessed at baseline, immediately before the
      challenge, after the challenge, and during an extended recovery period. Childhood
      maltreatment was assessed with a rigorous contextual interview and rating system.
      Adolescents with a history of maltreatment produced higher and more prolonged
      levels of cortisol in response to the challenge than did adolescents with no
      maltreatment, but only among those with a mild/moderate level of depression
      severity. Those with moderate/severe depression exhibited a blunted cortisol
      response regardless of child maltreatment history. These findings indicate that
      depression is a heterogeneous syndrome, and that both depression severity and
      child maltreatment history should be considered in studies examining biological
      stress reactivity.

PMID- 20688439
TI  - Preventing disruptive boys from becoming heavy substance users during
      adolescence: a longitudinal study of familial and peer-related protective
      factors.
AB  - Childhood disruptiveness is one of the most important antecedents of heavy
      substance use in adolescence, especially among boys. The first aim of the present
      study is to verify whether parental monitoring and friend conventionality protect
      disruptive boys from engaging in heavy substance-use in adolescence. The second
      purpose is to examine whether these protective effects are strengthened by
      attachment to parents or friends respectively. Finally, the third objective is to
      verify whether the expected protective effect of parental monitoring could be
      mediated through exposure to conventional friends. A sample of 1037 boys from low
      socioeconomic neighbourhoods was followed from childhood (age 6) to adolescence
      (age 15). Parent, teacher, and self-reported measures were used to measure
      disruptiveness, parental monitoring, family attachment, friend conventionality,
      and attachment to friends. Results suggest that parental monitoring and friends'
      conventionality mitigated the relationship between childhood disruptiveness and
      adolescence heavy substance use. Exposure to conventional friends further
      mediated the protective effect of parent monitoring. The postulated enhancement
      of attachment quality on the protective effect of parents or peer behaviors was
      not confirmed, but low attachment was related to heavier substance use in highly
      monitored disruptive boys. Parental monitoring, family attachment, and peer
      conventionality are factors amenable to intervention, and thus represent
      promising targets for future prevention strategies aimed at-risk boys. Our
      results underscore the importance of simultaneously addressing the behavioral and
      the affective dimensions in interventions with parents.

PMID- 20688440
TI  - Antimicrobial resistance and virulence gene profiles in multi-drug resistant
      enterotoxigenic Escherichia coli isolated from pigs with post-weaning diarrhoea.
AB  - This study aimed to characterize antimicrobial resistance and virulence genes in
      multi-drug resistant enterotoxigenic Escherichia coli (ETEC) isolates (n=117)
      collected from porcine post-weaning diarrhoea cases in Australia (1999-2005).
      Isolates were serotyped, antibiogram-phenotyped for 12 antimicrobial agents and
      genotyped by PCR for 30 plasmid-mediated antimicrobial resistance genes (ARGs),
      22 intestinal and 38 extraintestinal E. coli virulence genes (VGs). Nine
      serogroups were identified, the most prevalent being O149 (46.2%), O141 (11.2%)
      and Ont (31.6%). None of the isolates showed resistance to ceftiofur or
      enrofloxacin and 9.4% were resistant to florfenicol. No corresponding extended
      spectrum/AmpC beta-lactamase, fluoroquinolone or floR ARGs were detected. An
      antimicrobial resistance index (ARI) was calculated from the combined data with a
      weighting for each antimicrobial agent dependent upon its significance to human
      health. Serogroup O141 isolates had a significantly higher ARI due to an elevated
      prevalence of aminoglycoside ARGs and possession of more virulence genes (VGs),
      including ExPEC or EHEC adhesins (bmaE, sfa/focDE, fimH, ihA) in toxin-producing
      strains that lacked the normally associated F4 and F18 fimbriae. Few associations
      between ARGs and VGs were apparent, apart from tetC, sfa/focDE and ompT which,
      for a sub-set of O141 isolates, suggest possible plasmid acquisition from ExPEC.
      The multi-drug resistant ETEC ARG/VG profiles indicate a high probability of
      considerable strain and plasmid diversity, reflecting various selection pressures
      at the individual farm level rather than emergence and lateral spread of MDR
      resistant/virulent clones.

PMID- 20688442
TI  - Oral ultra-low dose continuous combined hormone replacement therapy with 0.5 mg
      17beta-oestradiol and 2.5 mg dydrogesterone for the treatment of vasomotor
      symptoms: results from a double-blind, controlled study.
AB  - OBJECTIVES: Guidelines recommend using the lowest effective dose of oestrogen for
      the management of vasomotor symptoms in postmenopausal women. The primary aim of
      this double-blind, multi-centre, randomised study was to assess the efficacy of
      oral ultra-low dose continuous combined hormone replacement therapy with 17beta
      oestradiol and dydrogesterone. STUDY DESIGN: 313 women with >=50 moderate to
      severe hot flushes during the previous week were randomised to 0.5 mg 17beta
      oestradiol/2.5 mg dydrogesterone (E 0.5 mg/D 2.5 mg), 1mg 17beta-oestradiol/5mg
      dydrogesterone (E 1mg/D 5 mg) or placebo for 13 weeks. The placebo group then
      switched to E 0.5 mg/D 2.5 mg for a further 39 weeks, whilst the other groups
      continued on the same treatment. RESULTS: After 13 weeks, the reduction in the
      number of moderate to severe hot flushes/day in the E 0.5 mg/D 2.5 mg group was
      greater than in the placebo group (-6.4 vs. -4.9, p<0.001) and comparable to that
      in the 1/5 mg group (-6.3). E 0.5 mg/D 2.5 mg and E 1mg/D 5 mg significantly
      improved the total Menopause Rating Scale score. The number of bleeding/spotting
      days was lower with E 0.5 mg/D 2.5 mg than with E 1 mg/D 5 mg. The overall
      amenorrhoea rate with E 0.5 mg/D 2.5 mg was 81%; this increased to 91% in months
      10-12. CONCLUSIONS: Continuous combined 0.5 mg 17beta-oestradiol and 2.5mg
      dydrogesterone was effective in alleviating vasomotor symptoms and improving
      quality of life, and was associated with a high amenorrhoea rate and a good
      tolerability profile.

PMID- 20688441
TI  - Cognitive changes associated with endocrine therapy for breast cancer.
AB  - Endocrine therapy in the setting of breast cancer has undoubtedly advanced
      clinical outcomes in this disease, but treatment with endocrine therapy is
      accompanied by a wide spectrum of side effects. It is of prime importance to
      understand and characterize these toxicities to facilitate clinical decision
      making. Somewhat surprisingly, there is a relative paucity of data pertaining to
      cognitive changes associated with endocrine therapy. In this article we review
      cognitive associated with two classes of endocrine therapy: (1) selective
      estrogen receptor modulators (SERMs; tamoxifen and raloxifene) and (2) aromatase
      inhibitors (AIs; anastrozole, letrozole, and exemestane). Companion studies to
      the Multiple Outcome of Raloxifene Evaluation (MORE), the Study of Tamoxifen and
      Raloxifene (STAR) and National Surgical Adjuvant Breast and Bowel Project (NSABP)
      P-1 trials provide relevant data to understand the effect of SERMs on cognition.
      In contrast, substudies of the Arimidex, Tamoxifen Alone or in Combination
      (ATAC), Tamoxifen and Exemestane Adjuvant Multinational (TEAM) and Breast
      International Group (BIG) 1-98 trials juxtapose cognitive effects of AIs against
      those of tamoxifen. These and other studies are examined herein to provide a
      comprehensive overview of the effect of endocrine therapy on cognition.

PMID- 20688443
TI  - Probabilistic evidential assessment of gunshot residue particle evidence (Part
      II): Bayesian parameter estimation for experimental count data.
AB  - Part I of this series of articles focused on the construction of graphical
      probabilistic inference procedures, at various levels of detail, for assessing
      the evidential value of gunshot residue (GSR) particle evidence. The proposed
      models--in the form of Bayesian networks--address the issues of background
      presence of GSR particles, analytical performance (i.e., the efficiency of
      evidence searching and analysis procedures) and contamination. The use and
      practical implementation of Bayesian networks for case pre-assessment is also
      discussed. This paper, Part II, concentrates on Bayesian parameter estimation.
      This topic complements Part I in that it offers means for producing estimates
      usable for the numerical specification of the proposed probabilistic graphical
      models. Bayesian estimation procedures are given a primary focus of attention
      because they allow the scientist to combine (his/her) prior knowledge about the
      problem of interest with newly acquired experimental data. The present paper also
      considers further topics such as the sensitivity of the likelihood ratio due to
      uncertainty in parameters and the study of likelihood ratio values obtained for
      members of particular populations (e.g., individuals with or without exposure to
      GSR).

PMID- 20688444
TI  - Role and limitations of 18F-FDG positron emission tomography (PET) in the
      management of patients with pancreatic lesions.
AB  - The 18-fluorine-18-fluoro-2-deoxyglucose Positron Emission Tomography coupled
      with computed tomography is a non invasive exploration. Several studies have
      shown that PET-CT has superior efficacy over conventional imaging techniques in
      distinguishing a benign pancreatic tumor from a malignant one. It contributes to
      the diagnosis of cancer in patients with a doubtful mass, much more in case of
      chronic pancreatitis. PET-CT is also an important help for the diagnosis of
      cystic tumors of the pancreas; the results can affect the management strategy. It
      is interesting for the endocrine tumors, particularly since the emergence of new
      markers. The aim of this paper is to summarize the role and limitations of 18-F
      FDG PET-CT in the management of patients with pancreatic lesions (adenocarcinoma,
      cystic tumors, endocrine tumors, etc...) concerning the malignancy diagnosis, the
      detection of metastases, the monitoring after non surgical treatments and to
      evaluate interpretation difficulties, particularly in case of diabetes or chronic
      pancreatitis.

PMID- 20688445
TI  - Carbon fibre and nitinol needles for MRI-guided interventions: first in vitro and
      in vivo application.
AB  - OBJECTIVE: To assess the artefact properties of a MR-compatible carbon fibre
      needle with a nitinol mandrin in vitro and to report first clinical experiences.
      MATERIALS AND METHODS: In vitro, the carbon fibre/nitinol needle was imaged at
      different angles against the main magnetic field (1.5T open bore magnet). A
      gradient echo MR fluoroscopy sequence (GRE: TR 9.3 ms, TE 3.12 ms, bandwidth 200
      Hz/pixel, flip-angle 12 degrees ) and a fast turbo spin echo sequence (FSE: TR
      412 ms, TE 9.7 ms, bandwidth 200 Hz/pixel, flip-angle 150 degrees ) were used.
      Artefact width, needle intensity contrast and needle tip location errors were
      assessed. In vivo, lumbar periradicular corticosteroid injections and one
      sclerotherapy were performed with carbon fibre needles (10 procedures) and with
      titanium alloy needles (2 procedures). The artefact sizes and contrasts were
      measured. RESULTS: In vitro, artefact diameters of the carbon fibre needle ranged
      from 3.3 to 4.6 mm, contrasts from 0.11 to 0.52, with larger artefact contrasts
      and widths with the GRE sequence. Needle tip location errors of -2.1 to -2.8 mm
      were observed. Decreasing angles to the main field lead to smaller artefacts. In
      vivo, the carbon fibre/nitinol needle produced smaller artefacts (mean width
      FSE/GRE: 2.8mm/4.6mm) with lower contrast (0.30-0.42) than the titanium alloy
      needle (mean width FSE/GRE: 4.1 mm/7.5 mm, contrast 0.60-0.73). CONCLUSIONS: The
      carbon fibre/nitinol needle is useful for performing MR-guided interventions at
      1.5T, producing more subtle artefacts than a titanium alloy needle, but with an
      incomplete depiction and thus inaccurate localization of the needle tip.

PMID- 20688446
TI  - FDG-PET/CT in advanced ovarian cancer staging: value and pitfalls in detecting
      lesions in different abdominal and pelvic quadrants compared with laparoscopy.
AB  - INTRODUCTION AND AIM: Ovarian carcinoma (OC) is a common cancer in the Western
      Countries, and an important cause of death in patients suffering with
      gynaecologic malignancies. The majority of patients present with advanced disease
      at the time of diagnosis. Treatment with debulking surgery followed by
      chemotherapy is the standard approach while chemotherapy is contemplated when
      surgery is not possible. A correct pre-operative staging is important to ensure a
      most appropriate management. Laparoscopy (LPS) is the standard diagnostic tool
      for the assessment of intraperitoneal infiltration but is invasive and requires
      general anaesthesia. FDG-PET/CT is increasingly used for staging different types
      of cancer, and the aim of this study is to assess the value of FDG-PET/CT in
      staging advanced OC and its sensitivity to detect lesions in different quadrants
      of the abdominal-pelvic area compared to laparoscopy. MATERIALS AND METHODS: From
      September 2004 till April 2008, 40 patients with high suspicion of OC were
      referred to our hospital for diagnostic LPS to explore the possibility of optimal
      debulking surgery. Those who were not suitable for surgery were referred for
      chemotherapy. Before chemotherapy, the patients underwent an FDG-PET/CT scan. The
      findings in 9 quadrants of abdominal-pelvic area (total 360 quadrants) for PET/CT
      and LPS were recorded and compared. RESULTS: In 14/360 areas (3.8%), surgical
      evaluation was not possible because of presence of adhesions, thus the number of
      areas explored by laparoscopy was 346. Tumour was found in 308 quadrants (38
      quadrants free of disease). PET/CT was positive in all 40 patients with true
      negative results in 26/346 quadrants (7.5%), and true positives results in
      243/346 quadrants (70.2%). False positive and negative PET/CT results were found
      in 12/346 and 65/346 quadrants, respectively. False positive PET/CT findings were
      evenly present in all quadrants. False negative PET/CT findings were present in
      31/109 (28.4%) upper abdominal quadrants (epigastrium and diaphragmatic areas).
      Final analysis showed a sensitivity and specificity for PET/TC of 78.9 and 68.4%
      respectively with a positive predictive value of 95.3%. A significant difference
      was noted between mean SUVmax associated with lesions smaller or larger than 0.5
      cm (p=0.006). CONCLUSION: Our results suggest that PET/CT may prove a useful tool
      for pre-surgical staging of ovarian cancer with a sensitivity and specificity of
      78 and 68%, respectively. However, it may be used in combination with laparoscopy
      for better results. PET/CT showed an adequate correlation between SUVmax values
      and laparoscopy findings of lesions>5mm, but a high rate of false negative
      results in lesions<5mm such as in carcinomatosis. PET/CT should be used carefully
      in early stage disease, with low risk of peritoneal infiltration, because of high
      rate of false positive results, to avoid unnecessary therapy procedures.

PMID- 20688447
TI  - The extremely halophilic bacterium Salicola marasensis IC10 accumulates the
      compatible solute betaine.
AB  - The extremely halophilic bacterium strain IC10 was isolated from a solar saltern
      on Isla Cristina (southern Spain). Phylogenetic, genotypic and phenotypic data
      supported the inclusion of this strain in the species Salicola marasensis. An
      analysis of intracellular organic osmotic solutes showed glycine betaine to be
      present, contributing to the overall osmotic balance, and this was the only
      compatible solute accumulated when S. marasensis IC10 was grown over a wide range
      of external NaCl concentrations (10-25%, w/v).

PMID- 20688448
TI  - Unambiguous identification of superparamagnetic iron oxide particles through
      quantitative susceptibility mapping of the nonlinear response to magnetic fields.
AB  - Superparamagnetic iron oxide (SPIO) particles generate signal void regions on
      gradient echo images due to their strong magnetization. In practice, the signal
      void region might be indistinguishable from that generated by air. However, the
      response of SPIO to an externally applied magnetic field is nonlinear.
      Magnetization of SPIO saturates at around 1 T while magnetization of water and
      air increase linearly with field strength. Phantom experiment and mice
      experiments demonstrated the feasibility of a nonambiguous identification of
      superparamagnetic contrast agents.

PMID- 20688449
TI  - Brain metabolism and cognitive impairment in HIV infection: a 3-T magnetic
      resonance spectroscopy study.
AB  - BACKGROUND AND PURPOSE: Human immunodeficiency virus (HIV)-associated dementia
      (HAD) has been extensively studied using magnetic resonance spectroscopy (MRS) at
      field strengths of 1.5 T. Higher magnetic field strengths (such as 3 T) allow for
      more reliable determination of certain compounds, such as glutamate (Glu) and
      glutamine (Gln). The current study was undertaken to investigate the utility of 3
      T MRS for evaluating HIV+ patients with different levels of cognitive impairment
      with emphasis on the measurement of Glu and Glx (the sum of Glu and Gln).
      METHODS: Eighty-six HIV+ subjects were evaluated at 3 T using quantitative short
      echo time single-voxel MRS of frontal white matter (FWM) and basal ganglia (BG).
      Subjects were divided into three groups according to the Memorial Sloan Kettering
      (MSK) HIV dementia stage: 21 had normal cognition (NC) (MSK 0), 31 had mild
      cognitive impairment (MCI) without dementia (clinical MSK stage=0.5), and 34 had
      dementia (HAD) (MSK>=1). HIV+ subjects had also undergone standardized cognitive
      testing covering the domains of executive function, verbal memory, attention,
      information processing speed and motor and psychomotor speed. Between-group
      differences in metabolite levels in FWM and BG were evaluated using ANOVA.
      Pearson correlation coefficients were used to explore the associations between
      the Glu and Glx metabolites and neurocognitive results. RESULTS: FWM Glx was
      lower in HAD (8.1 +/- 2.1 mM) compared to both the MCI (9.17 +/- 2.1 mM) and NC
      groups (10.0 +/- 1.6 mM) (P=.006). FWM myo-inositol (mI) was higher in HAD (4.15
      +/- 0.75 mM) compared to both MCI (3.86 +/- 0.85 mM) and NC status (3.4 +/- 0.67
      mM) (P=.006). FWM Glx/creatine (Cr) was lower and FWM mI/Cr was significantly
      higher in the HAD compared to the MCI and NC groups (P=.01 and P=.004,
      respectively). BG N-acetyl aspartate (NAA) was lower in the HAD group (6.79 +/-
      1.53 mM), compared to the MCI (7.5 +/- 1.06 mM) and NC (7.6 +/- 1.01 mM) groups
      (P=.036). Significant negative correlations were observed between Glu, Glx and
      NAA concentrations with Trail-Making Test B (P=.006, P=.0001 and P=.007,
      respectively), and significant positive correlation was found with the Digit
      symbol test (P=.02, P=.002 and P=.008, respectively). FWM Glx and NAA
      concentrations showed negative correlation with Grooved Pegboard nondominant hand
      (P=.02 and P=.04, respectively). CONCLUSION: Patients with HAD have lower levels
      of Glx concentrations and Glx/Cr ratio in FWM, which was associated with impaired
      performance in specific cognitive domains, including executive functioning, fine
      motor, attention and working memory performance. Three-Tesla MRS measurements of
      Glx may be a useful indicator of neuronal loss/dysfunction in patients with HIV
      infection.

PMID- 20688450
TI  - MR Imaging of total hip arthroplasty: comparison among sequences to study the
      sciatic nerve at 1.5 T.
AB  - PURPOSE: This study was done to test a series of MR sequences for evaluating the
      sciatic nerve after total hip arthroplasty (THA). MATERIAL AND METHODS: The study
      protocol was approved by the institutional review board. Informed consent was
      obtained from all patients. Twenty-five patients (11 men and 14 women mean age:
      62.3+/-5.7 years) with THA were included in this prospective study. MRI protocol
      included sequences that were preliminarily tailored for nerve imaging in patients
      with THA: proton density (PD)-weighted turbo SE, T1-weighted turbo SE (TSE) 3 mm
      thickness, T1-weighted turbo SE (TSE) 6 mm thickness, T1-weighted turbo SE with
      high bandwidth (TSE hBW), T2- weighted TSE, T2-weighted with fat saturation and
      short-tau inversion recovery (STIR). For each sequence, we evaluated the
      visibility of the sciatic nerve using a semiquantitative score (0=total masking;
      1=insufficient visibility; 2=sufficient visibility; 3=optimal visibility). The
      sum of the scores given to each sequence was divided by the maximal sum,
      obtaining a percentage visibility index. Friedman and sign tests were used for
      statistical analysis. RESULTS: MR examination time was approximately 40 min. No
      patients reported pain, heat or symptoms related to nerve stimulation. The
      visibility index ranged between 88% and 70% for the first four sequences. The T1
      weighted TSE hBW sequence had the best visibility index (P<.05). The visibility
      indexes of the first four sequences were significantly higher (P<.004, sign test)
      than those of the remaining three sequences. CONCLUSION: The sciatic nerve could
      be studied at 1.5 T in patients following THA. The nerve is better visualized
      with T1-weighted TSE hBW sequences. On T2-weighted sequences and STIR, the
      visibility of the nerve is low.

PMID- 20688451
TI  - An online coupled cell membrane chromatography with LC/MS method for screening
      compounds from Aconitum carmichaeli Debx. acting on VEGFR-2.
AB  - An online analytical method coupling high expression vascular endothelial growth
      factor receptor (VEGFR) cell membrane chromatography (VEGFR-CMC) with high
      performance liquid chromatography mass spectrometry (LC/MS) for screening and
      identification of active component from traditional Chinese herb Aconitum
      carmichaeli Debx. acting on VEGFR-2 was established. Through a 10-port column
      switcher, factions separated by VEGFR-CMC column (first dimension) were
      transferred and were adsorbed on an enrichment column. Then, these fractions were
      sent into LC/MS system (second dimension) immediately and directly for separation
      and preliminary identification, respectively. Sunitinib malate (SN) was used as
      positive control, while nifedipine (NF), dexamethasone acetate (DX), methoxyamine
      hydrochloride (MT) and atenolol (AT) as negative controls. The specification of
      this VEGFR-CMC-online-LC/MS method was validated by competitive displacement
      test. As a result, mesaconitine (MSC), aconitine (AC), and hypaconitine (HPC)
      were identified as the active constituents acting on VEGFR-2. The in vitro
      inhibition activity of starting extract of Aconitum carmichaeli Debx., MSC, AC,
      and HPC on HEK293/VEGFR cell viability by MTT test, separately. The in vitro
      inhibition activity of MSC, AC, and HPC on vascular endothelial growth factor
      (VEGF) secretion of HEK293/VEGFR cell was tested by VEGF-ELISA assay. The
      screening results given by the system offered additional exemplification
      supporting this online coupling method and gave new evidence to the development
      of anti-tumor drug from natural products.

PMID- 20688452
TI  - Validation of a fast gas chromatographic method for the study of semiochemical
      slow release formulations.
AB  - The validation of a fast GC-FID analytical method for the quantitative
      determination of semiochemical sesquiterpenes (E-beta-farnesene and beta
      caryophyllene) to be used in an integrated pest management approach is described.
      Accuracy profiles using total error as decision criteria for validation were used
      to verify the overall accuracy of the method results within a well defined range
      of concentrations and to determine the lowest limit of quantification for each
      analyte. Furthermore it allowed to select a very simple and reliable regression
      model for calibration curve for the quantification of both analytes as well as to
      provide measurement uncertainty without any additional experiments. Finally, this
      validated method was used for the quantification of semiochemicals in slow
      release formulations. The goal was to verify the protection efficiency of
      alginate gel beads formulations against oxidation and degradation of
      sesquiterpenes. The results showed that the alginate beads are adequate slow
      release devices which protect the bio-active molecules during at least twenty
      days.

PMID- 20688453
TI  - Rapid analysis of trace levels of flavins by pressurized capillary
      electrochromatography-laser induced fluorescence detection with sulfonated N
      octadecyl methacrylate monolith.
AB  - In this paper, pressurized capillary electrochromatography (pCEC) with laser
      induced fluorescence detection (LIF) was demonstrated as a viable approach for
      the separation and determination of trace flavins in human plasma, where flavins
      tend to be degraded ex vivo. Using a sulfonated N-octadecyl methacrylate
      monolithic column in isocratic pCEC separation, symmetrical peak shapes and rapid
      separation could be obtained in a weakly acidic mobile phase. Baseline separation
      of riboflavin, flavin mononucleotide and flavin adenine dinucleotide could be
      achieved within 4.5 min in a mobile phase containing 60% (v/v) acetonitrile and
      40% (v/v) of 20 mmol L(-1) phosphate buffer (pH 4.0), with -22 kV of applied
      voltage and 290 psi of supplementary pressure and 0.02 mL min(-1) of flow rate.
      Based on a 473 nm laser diode double pumped solid state source, flavins could be
      determined by LIF with the detection limit (LOD) as low as 0.5 nmol L(-1)
      (S/N=3). The concentration ranges were 0.005-2 micromol L(-1) for RF and FMN, and
      0.02-40 micromol L(-1) for FAD. Owing to the weakly acidic condition selected in
      this experiment, the high fluorescence quantum yields and good stability of
      flavins contributed to a preferable analysis. Combined with a simple clean-up
      procedure, this method has been proved to be effective for the rapid and
      selective analysis of trace levels of flavins in human plasma without sample
      preconcentration.

PMID- 20688454
TI  - Media and memory: the efficacy of video and print materials for promoting patient
      education about asthma.
AB  - OBJECTIVE: We examined the effects of presentation medium on immediate and
      delayed recall of information and assessed the effect of giving patients take
      home materials after initial presentations. METHODS: Primary-care patients
      received video-based, print-based or no asthma education about asthma symptoms
      and triggers and then answered knowledge-based questions. Print participants and
      half the video participants received take-home print materials. A week later,
      available participants completed the knowledge assessment again. RESULTS:
      Participants receiving either intervention outperformed controls on immediate and
      delayed assessments (p<0.001). For symptom-related information, immediate
      performance did not significantly differ between print and video participants. A
      week later, receiving take-home print predicted better performance (p<0.05), as
      did self-reported review among recipients of take-home print (p<0.01). For
      content about inhaler usage, although video watchers outperformed print
      participants immediately after seeing the materials (p<0.001), a week later these
      two groups' performance did not significantly differ. Among participants given
      take-home materials, review predicted marginally better recall (p=0.06).
      CONCLUSION: Video and print interventions can promote recall of health-related
      information. Additionally, reviewable materials, if they are utilized, may
      improve retention. PRACTICE IMPLICATIONS: When creating educational tools,
      providers should consider how long information must be retained, its content, and
      the feasibility of providing tangible supporting materials.

PMID- 20688455
TI  - The path to safe and reliable healthcare.
AB  - The ability to deliver safe and reliable healthcare is the goal of all healthcare
      delivery systems. To bridge the current performance gaps in quality and safety,
      organizations need to apply a systematic model that effectively addresses both
      culture and reliable processes of care. The model described in this article
      provides a comprehensive approach to improving the quality of care in any
      clinical domain. It also provides a roadmap for people working in clinical
      improvement to assess the strengths and current needs within their care systems,
      so they can be strategic and systematic in their work, essential elements for
      success. The concepts and tools provided can be readily applied to improve the
      quality and safety of care delivered.

PMID- 20688456
TI  - Teaching residents to communicate: the use of a telephone triage system in an
      academic ambulatory clinic.
AB  - OBJECTIVE: This study evaluated the use of a telephone triage system in an
      academic primary care clinic and its impact on communication, patient management
      and satisfaction. METHODS: A "telephone clinic" was created using a triage nurse
      to answer patients' calls to an academic primary care clinic, staffed by house
      staff physicians. Chart reviews were conducted of all medical records of patients
      who called and were referred to the telephone clinic during a six month period. A
      total of 1135 patient calls were monitored. Using a random selection process, 366
      patient calls were studied and 42% of these patients were called back two weeks
      after the initial call and were interviewed. RESULTS: Of the 336 calls, 68% of
      the calls were serious enough to be referred to a house staff physician. Symptom
      complaints accounted for 64% of the telephone calls; 4% of patients were sent to
      the emergency room or admitted to the hospital directly based on the information
      from the call. Telephone calls enhanced patients' access to specialty care
      consultative services and 14% of patients who called received a new medication
      prescription. Patients' satisfaction with the communication and the overall care
      provided by the "telephone clinic" was highly rated. CONCLUSION: The telephone
      contact initiated by the patients resulted in expedited access for patients whose
      symptoms were serious enough to require immediate referral to the emergency room
      or direct hospital admission. PRACTICE IMPLICATIONS: In a primary care practice,
      the telephone can be a major source of communication for practitioners, office
      staff and patients. The creation of a "telephone clinic" which utilizes nurses
      and house staff physicians trained and dedicated to telephone communication
      directly with patients resulted in more efficient management and greater
      satisfaction for patients.

PMID- 20688457
TI  - An exploration of patient decision-making for autologous breast reconstructive
      surgery following a mastectomy.
AB  - OBJECTIVE: The aim of this study was to examine patients' experiences of the
      decision to undergo breast reconstructive surgery following mastectomy. METHOD:
      21 Women, who had undergone reconstruction, took part in a semi-structured
      qualitative interview, which examined the participants' experience of the
      decision-making process. The recorded interviews were transcribed verbatim and
      analyzed using "framework analysis". RESULTS: Women who underwent immediate
      reconstruction spoke of the convenience of undergoing only one operation with
      regards to juggling work and childcare arrangements. For women who underwent
      delayed reconstructive surgery the reasons centre on dissatisfaction with wearing
      prosthesis. Others spoke of no choice, as immediate reconstruction was not
      offered as an option. However both groups did report similar influential factors
      and received and used similar informational content and informational sources in
      order to make their decision. CONCLUSION: The study outlines the different
      motivations for undergoing immediate or delayed breast reconstruction and
      highlights that there is not always a choice offered to patients. PRACTICE
      IMPLICATIONS: Future patients who are considering breast reconstruction should be
      provided with the relevant information to make a well informed decision and may
      benefit from different methods of information delivery that could include
      decision aids such as informational booklets, photographs, and videos.

PMID- 20688458
TI  - SACA: Software Assisted Call Analysis--an interactive tool supporting content
      exploration, online guidance and quality improvement of counseling dialogues.
AB  - OBJECTIVE: Nearly 30,000 individual inquiries are answered annually by the
      telephone cancer information service (CIS, KID) of the German Cancer Research
      Center (DKFZ). The aim was to develop a tool for evaluating these calls, and to
      support the complete counseling process interactively. METHODS: A novel software
      tool is introduced, based on a structure similar to a music score. Treating the
      interaction as a "duet", guided by the CIS counselor, the essential contents of
      the dialogue are extracted automatically. For this, "trained speech recognition"
      is applied to the (known) counselor's part, and "keyword spotting" is used on the
      (unknown) client's part to pick out specific items from the "word streams". The
      outcomes fill an abstract score representing the dialogue. RESULTS: Pilot tests
      performed on a prototype of SACA (Software Assisted Call Analysis) resulted in a
      basic proof of concept: Demographic data as well as information regarding the
      situation of the caller could be identified. CONCLUSION: The study encourages
      following up on the vision of an integrated SACA tool for supporting calls online
      and performing statistics on its knowledge database offline. PRACTICE
      IMPLICATIONS: Further research perspectives are to check SACA's potential in
      comparison with established interaction analysis systems like RIAS.

PMID- 20688459
TI  - Basal measures of insulin sensitivity and insulin secretion and simplified
      glucose tolerance tests in dogs.
AB  - There is need for simple, inexpensive measures of glucose tolerance, insulin
      sensitivity, and insulin secretion in dogs. The aim of this study was to estimate
      the closeness of correlation between fasting and dynamic measures of insulin
      sensitivity and insulin secretion, the precision of fasting measures, and the
      agreement between results of standard and simplified glucose tolerance tests in
      dogs. A retrospective descriptive study using 6 naturally occurring obese and 6
      lean dogs was conducted. Data from frequently sampled intravenous glucose
      tolerance tests (FSIGTTs) in 6 obese and 6 lean client-owned dogs were used to
      calculate HOMA, QUICKI, fasting glucose and insulin concentrations. Fasting
      measures of insulin sensitivity and secretion were compared with MINMOD analysis
      of FSIGTTs using Pearson correlation coefficients, and they were evaluated for
      precision by the discriminant ratio. Simplified sampling protocols were compared
      with standard FSIGTTs using Lin's concordance correlation coefficients, limits of
      agreement, and Pearson correlation coefficients. All fasting measures except
      fasting plasma glucose concentration were moderately correlated with MINMOD
      estimated insulin sensitivity (|r| = 0.62-0.80; P < 0.03), and those that
      combined fasting insulin and glucose were moderately closely correlated with
      MINMOD-estimated insulin secretion (r = 0.60-0.79; P < 0.04). HOMA calculated
      using the nonlinear formulae had the closest estimated correlation (r = 0.77 and
      0.74) and the best discrimination for insulin sensitivity and insulin secretion
      (discriminant ratio 4.4 and 3.4, respectively). Simplified sampling protocols
      with half as many samples collected over 3 h had close agreement with the full
      sampling protocol. Fasting measures and simplified intravenous glucose tolerance
      tests reflect insulin sensitivity and insulin secretion derived from frequently
      sampled glucose tolerance tests with MINMOD analysis in dogs.

PMID- 20688460
TI  - Effect of hyperlipidemia on 11beta-hydroxysteroid-dehydrogenase, glucocorticoid
      receptor, and leptin expression in insulin-sensitive tissues of cats.
AB  - Glucocorticoid (GC) action depends on GC plasma concentration, cellular GC
      receptor expression, and the pre-receptor hormone metabolism catalyzed by 11beta
      hydroxysteroid dehydrogenase (11beta-HSD). 11beta-Hydroxysteroid dehydrogenase
      exists in 2 isoforms; 11beta-HSD1 converts inactive cortisone to cortisol, and
      11beta-HSD2 converts cortisol to cortisone. Increasing evidence in humans and
      experimental animals suggests that altered tissue cortisol metabolism may
      predispose to diabetes mellitus (DM). Once DM is established, hyperglycemia and
      hyperlipidemia may further maintain the abnormal metabolism of cortisol. To gain
      further insight in this regard, healthy cats were infused for 10 d with lipids (n
      = 6) or saline (n = 5). At the end of the infusion period, tissue samples from
      adipose tissue (visceral, subcutaneous), liver, and muscle were collected to
      determine mRNA expression of 11beta-HSD1, 11beta-HSD2, and GC receptor by real
      time reverse-transcriptase polymerase chain reaction; blood samples were
      collected to determine plasma cortisol and leptin concentrations. Lipid infusion
      resulted in greater 11beta-HSD1 expression and lower GC receptor expression in
      visceral and subcutaneous adipose tissue, and lower 11beta-HSD2 expression in
      visceral adipose tissue and liver. Plasma cortisol did not differ. Leptin and
      body weight increased in lipid-infused cats. In spite of comparable circulating
      cortisol levels, up-regulation of 11beta-HSD1 and down-regulation of 11beta-HSD2
      expression may result in increased tissue cortisol concentrations in fat depots
      of hyperlipidemic cats. Down-regulation of GC receptor may represent a self
      protective mechanism against increased tissue cortisol levels. In conclusion,
      hyperlipidemia has a profound effect on 11beta-HSD expression and supports the
      connection between high lipid concentrations and tissue cortisol metabolism.

PMID- 20688461
TI  - Expression of mRNA for proglucagon and glucagon-like peptide-2 (GLP-2) receptor
      in the ruminant gastrointestinal tract and the influence of energy intake.
AB  - Glucagon-like peptide-2 (GLP-2) is a potent trophic gut hormone, yet its function
      in ruminants is relatively unknown. Experiment 1 was conducted as a pilot study
      to establish the presence of GLP-2 in ruminants and to ascertain whether it was
      responsive to increased nutrition, as in non-ruminants. Concentrations of intact
      GLP-2 in the blood and gut epithelial mRNA expression of proglucagon (GCG) and
      the GLP-2 receptor (GLP2R) were measured in 4 ruminally, duodenally, and ileally
      cannulated steers. Steers were fed to meet 0.75 x NE(M) for 21 d, and then
      increased to 1.75 x NE(M) requirement for another 29 d. Blood samples and
      ruminal, duodenal, and ileal epithelium biopsies were collected at low intake
      (Days -6 and -3), acute high intake (Days 1 and 3), and chronic high intake (Days
      7 and 29) periods. Experiment 2 investigated the mRNA expression pattern of GCG
      and GLP2R in epithelial tissue obtained from the forestomachs (rumen, omasum, and
      abomasum) and intestines (duodenum, jejunum, ileum, and colon) of 18 forage-fed
      Angus steers (260 kg BW). In Experiments 1 and 2, real-time polymerase chain
      reaction showed that expression of GCG and GLP2R mRNA was detectable in
      forestomach tissues, but expression was greater (P < 0.001) in small intestinal
      and colon tissue. High energy intake tended (P = 0.07) to increase plasma GLP-2
      during the acute period and was paralleled by a 78% increase (P = 0.07) in ileal
      GCG mRNA expression. After this initial adaptation, duodenal GCG mRNA expression
      increased (P = 0.08) during the chronic high intake period. Duodenal GLP2R mRNA
      expression was not affected by energy intake, but ileal GLP2R expression was
      increased after 29 d of high energy intake compared to both the low and acute
      high intake periods (P = 0.001 and P = 0.01, respectively). These data
      demonstrate that cattle express GCG and GLP2R mRNA primarily in small intestinal
      and colon tissues. Increased nutrient intake increases ileal GCG mRNA and plasma
      GLP-2, suggesting that GLP-2 may play a role in the trophic response of the
      ruminant gastrointestinal tract to increased feed intake.

PMID- 20688462
TI  - Effect of recombinant human TSH on the uptake of radioactive iodine ((123)I) by
      the thyroid gland in healthy beagles.
AB  - In human medicine, recombinant human thyroid-stimulating hormone (rhTSH)
      increases thyroid radioactive iodine uptake (RAIU), allowing radioiodine-131
      ((131)I) dose reduction and greater efficacy in the treatment of differentiated
      thyroid cancer and multinodular goiter. The goal of this study was to evaluate
      the effect of rhTSH, administered 24 h and 48 h before radioiodine-123 ((123)I),
      on the thyroid RAIU in healthy dogs. Seven healthy euthyroid beagles were
      randomly allocated to 3 groups (2 groups of 2 dogs and 1 group of 3 dogs) in a
      prospective, blinded, crossover study. At Week 1, 1 group received (123)I for a
      baseline RAIU; 1 group received 100 MUg of rhTSH IV 24 h before (123)I, and 1
      group received 100 MUg of rhTSH IV 48 h before (123)I. All dogs received 37 MBq
      of radioactive (123)I IV, and thyroid RAIU was determined 8 h, 24 h, and 48 h
      thereafter. The study was designed in such a manner that each dog received the 3
      treatments and a wash-out period of 3 wk was respected in between. Blood samples
      were taken for measurement of serum total thyroxine (TT4) and thyrotropin (TSH)
      concentrations at baseline and 6 h, 12 h, 24 h, and 48 h after rhTSH
      administration. Recombinant human TSH caused no significant change on thyroid
      RAIU. The overall mean thyroid RAIU significantly decreased during the study
      independent of the treatment. Recombinant human TSH significantly increased serum
      TT4 concentration, which peaked 6 h after rhTSH administration. Compared to
      baseline, serum TSH concentration remained higher at 6 h, 12 h, 24 h, and 48 h.
      However, a statistically significant difference was reached only at 6 h and 12 h
      after rhTSH administration. No adverse effects of rhTSH were observed during the
      study. Further studies are needed to determine the best timing and dosage of
      administration of rhTSH in healthy and thyroid carcinoma dogs.

PMID- 20688463
TI  - Cortisol release, heart rate, and heart rate variability in transport-naive
      horses during repeated road transport.
AB  - Domestic animals are often repeatedly exposed to the same anthropogenic
      stressors. Based on cortisol secretion and heart rate, it has been demonstrated
      that transport is stressful for horses, but so far, changes in this stress
      response with repeated road transport have not been reported. We determined
      salivary cortisol concentrations, fecal cortisol metabolites, cardiac beat-to
      beat (RR) interval, and heart rate variability (HRV) in transport-naive horses (N
      = 8) transported 4 times over a standardized course of 200 km. Immunoreactive
      salivary cortisol concentrations always increased in response to transport (P <
      0.001), but cortisol release decreased stepwise with each transport (P < 0.05).
      Concentrations of fecal cortisol metabolites increased from 55.1 +/- 4.6 ng/g
      before the first transport to 161 +/- 17 ng/g the morning after (P < 0.001).
      Subsequent transport did not cause further increases in fecal cortisol
      metabolites. In response to the first transport, mean RR interval decreased with
      loading of the horses and further with the onset of transport (1551 +/- 23, 1304
      +/- 166, and 1101 +/- 123 msec 1 d before, immediately preceding, and after 60-90
      min of transport, respectively; P < 0.05). Decreases in RR interval during
      subsequent transports became less pronounced (P < 0.001). Transport was
      associated with a short rise in the HRV variable standard deviation 2 (P < 0.001
      except transport 1), indicating sympathetic activation. No consistent changes
      were found for other HRV variables. In conclusion, a transport-induced stress
      response in horses decreased with repeated transport, indicating that animals
      habituated to the situation, but an increased cortisol secretion remained
      detectable.

PMID- 20688465
TI  - Clinical characteristics and outcomes of patients with 2009 influenza A(H1N1)
      virus infection with respiratory failure requiring mechanical ventilation.
AB  - PURPOSE: The purpose of the study was to describe the clinical characteristics
      and outcomes of critically ill patients with 2009 influenza A(H1N1). METHODS: An
      observational study of patients with confirmed or probable 2009 influenza A(H1N1)
      and respiratory failure requiring mechanical ventilation was performed. RESULTS:
      We studied 96 patients (mean age, 45 [14] years [mean, SD]; 44% female). Shock
      and acute respiratory distress syndrome were diagnosed during the first 72 hours
      of admission in 43% and 72% of patients, respectively. Noninvasive positive
      pressure ventilation was used in 45% of the patients, but failed in 77% of them.
      Bacterial pneumonia was diagnosed in 33% of cases, 8% during the first week (due
      to community-acquired microorganisms) and 25% after the first week (due to gram
      negative bacilli and resistant gram-positive cocci). Intensive care unit
      mortality was 50%. Nonsurvivors differed from survivors in the prevalence of
      cardiovascular, respiratory, and hematologic failure on admission and late
      pneumonia. Reported causes of death were refractory hypoxia, multiorgan failure,
      and shock (50%, 38%, and 12% of all causes of death, respectively). CONCLUSIONS:
      Patients with 2009 influenza A(H1N1) and respiratory failure requiring mechanical
      ventilation often present with clinical criteria of acute respiratory distress
      syndrome and shock. Bacterial pneumonia is a frequent complication. Mortality is
      high and is primarily due to refractory hypoxia.

PMID- 20688464
TI  - Alveolar fluid clearance is faster in women with acute lung injury compared to
      men.
AB  - PURPOSE: Studies suggest that there is a sex difference in the development and
      outcomes of acute lung injury (ALI). Few studies have directly addressed the
      association of sex and alveolar fluid clearance (AFC), a process that is critical
      to ALI resolution. MATERIALS AND METHODS: To test the hypothesis that female sex
      is associated with an increased AFC rate, we measured AFC rates in 150
      mechanically ventilated patients with acute pulmonary edema and a pulmonary edema
      fluid-to-plasma protein ratio (EF/PL) diagnostic of low permeability (EF/PL
      <0.65, n = 69) or high permeability (EF/PL >=0.65, n = 81) edema. We measured
      protein concentration in serial samples of undiluted EF collected within 6 hours
      of intubation and calculated net rate of AFC. In addition, plasma levels of
      receptor for advanced glycation end products were measured as a surrogate marker
      for alveolar epithelial injury. RESULTS: In patients with ALI, women had higher
      rates of net AFC at 4 hours compared to men (11.9% per hour vs 4.3% per hour, P =
      .017) and more women had maximal rates of AFC. There were no differences in
      circulating levels of receptor for advanced glycation end products between men
      and women. CONCLUSIONS: These findings may have significant implications for
      future ALI studies and potential therapies.

PMID- 20688466
TI  - A Good War? Exploring British veterans' moral evaluation of deployment.
AB  - Historically, war trauma research has concentrated on the relationship between
      level of exposure and development of post-traumatic symptoms. More recently, it
      has been recognized that intra- and interpersonal differences can mediate how
      service personnel are affected by their experiences. This paper is a qualitative
      study exploring moral evaluations of 30 British male veterans towards their
      deployment in conflicts from WWII to the most recent Iraq War (2003-2009).
      Retrospective thematic analysis is used to explore moral evaluation and societal
      support. Four categories emerged based on veterans' moral evaluation of
      deployment: justifiable, implicitly justifiable, unclear, and unjustifiable.
      Analysis revealed broad differences between these groups. Veterans able to
      justify their experiences reported more positive aspects of both deployment and
      societal support than those unable to justify their deployment. These findings
      make clear the importance of future research exploring the interactions between
      civilians and service personnel, and the impact this has on mental health.

PMID- 20688467
TI  - Japanese version of school form of the ADHD-RS: an evaluation of its reliability
      and validity.
AB  - Using the Japanese version of school form of the ADHD-RS, this survey attempted
      to compare the scores between the US and Japan and examined the correlates of
      ADHD-RS. The classroom teachers of 7414 children (3842 males and 3572 females)
      evaluated all the children's behaviors. A confirmed factor analysis of ADHD-RS
      confirmed the two-factor solution (Inattentive and Hyperactive-Impulsive) same as
      previous studies. ADHD-RS scores were not related to IQ, but were associated with
      standardized achievement test scores. Males showed stronger ADHD tendencies than
      did the females, and the males tended to score lower as they grew older. Our
      comparison of the scores between the US and Japan found the Japanese children
      scored lower than did their US children. Japanese version of school form of the
      ADHD-RS with good reliability and validity was developed. More researches of ADHD
      in Japanese children are required.

PMID- 20688468
TI  - A computational model of a global neuronal workspace with stochastic connections.
AB  - This paper presents a model of long-range cortical communication by means of a
      global neuronal workspace similar to that proposed by Dehaene and Naccache
      (2001). The model resembles that of Shanahan (2008), which was based on
      reverberating circuits of one-to-one connections, but uses a stochastic wiring
      regime in place of the highly regular scheme used there. The paper offers a
      systematic analysis of the influence of certain parameters on the dynamics of
      networks built according to this regime. Armed with a fuller understanding of the
      origins of the observed behaviour in the model, the qualitative behaviour of the
      previous model is replicated, and further unexplored choices are examined for
      ongoing work.

PMID- 20688469
TI  - Myocardial tissue Doppler velocity imaging in children: comparative study between
      two ultrasound systems.
AB  - BACKGROUND: The investigators compared pulsed-wave tissue Doppler (PWTD) and
      color tissue Doppler (CTD) ventricular tissue velocities obtained using Vivid 7
      (GE) and iE33 (Philips) ultrasound systems within a 30-minute time frame and
      examined interobserver and intraobserver variability. METHODS: Longitudinal PWTD
      and CTD images were prospectively acquired in 49 children from the base of the
      right and left ventricular free wall and septum and stored for offline analysis.
      RESULTS: Intraobserver and interobserver coefficients of variation for PWTD
      velocities ranged from 4% to 6% and 5% to 10% for GE and from 1% to 10% and 2% to
      14% for Philips, respectively. Intraobserver and interobserver coefficients of
      variation for CTD velocities ranged from 4% to 15% and 6% to 24% for GE and from
      6% to 19% and 7% to 25% for Philips, respectively. Mean biases between the two
      systems for PWTD velocities, expressed as percentage differences, were around 0%,
      with the narrowest limits of agreement for systolic velocities at the septal
      annulus and the widest limits of agreement for early diastolic velocities at the
      lateral tricuspid valve annulus, respectively. Peak CTD-derived velocities were
      significantly and consistently lower for Philips compared with GE. CONCLUSIONS:
      Agreement between GE-derived and Philips-derived PWTD velocities was reasonable,
      whereas CTD-derived velocities differed substantially.

PMID- 20688470
TI  - Effects of prolonged exercise on left ventricular mechanical synchrony in long
      distance runners: importance of previous exposure to endurance races.
AB  - BACKGROUND: Prolonged exercise has been shown to lead to elevated levels of
      cardiac troponin and altered cardiac function on echocardiography. It is not
      known if cardiac synchrony is altered by prolonged exercise. The aims of this
      study were to assess changes in intra-left ventricular mechanical synchrony and
      circulating levels of cardiac troponin following prolonged exercise and to
      evaluate the importance of prior exposure to endurance racing. METHODS: Forty
      three male participants in a 30-km cross-country race (20 new participants at
      this event [median, 3 previous endurance races] age matched against 23 repeat
      participants [median, 31 previous endurance events]) were assessed prospectively
      1 to 2 days before and 24 hours after the race using troponin T and Doppler
      tissue imaging analyzing the standard deviation of time to peak myocardial
      systolic velocity (T(s)-SD) in a six-basal, six-midventricular segment model
      measuring myocardial synchrony. The insertion/deletion (I/D) polymorphism of the
      angiotensin-converting enzyme (ACE) gene was also analyzed, as I allele carriers
      reportedly have superior endurance performance, while the D allele predisposes to
      renin-angiotensin system-induced cardiac remodeling. RESULTS: Prerace troponin T
      was undetectable in all runners, and postrace levels were higher in new runners
      (median, 0.03 microg/L; interquartile range [IQR], 0.01-0.04 microg/L) than in
      repeat runners (median, 0.01 microg/L; IQR, 0.01-0.02 microg/L) (P = .03).
      Although new and repeat runners had similar T(s)-SD at baseline (32 msec [IQR, 22
      43 msec] vs 34 msec [IQR, 29-45 msec], P = .13), dyssynchrony increased only in
      new runners (40 msec [IQR, 31-47 msec], P < .001; in repeat runners, median, 38
      msec [IQR, 29-43 msec], P = .30; median relative difference, +13% vs +5%, P =
      .02). ACE genotype distribution was similar in both groups. Multivariate analysis
      showed that (1) a lack of prior endurance exposure; (2) more copies of the ACE D
      allele; and (3) lower peak systolic velocity were independent predictors of
      postrace dyssynchrony (P < .05 for all). CONCLUSION: Prolonged exertion increased
      ventricular mechanical dyssynchrony in new endurance participants and in ACE D
      allele carriers. The long-term impact of such changes warrants future study.

PMID- 20688471
TI  - Relative to the general US population, chronic diseases are associated with
      poorer health-related quality of life as measured by the Patient-Reported
      Outcomes Measurement Information System (PROMIS).
AB  - OBJECTIVES: The Patient-Reported Outcomes Measurement Information System (PROMIS)
      allows assessment of the impact of chronic conditions on health-related quality
      of life (HRQL) across diseases. We report on the HRQL impact of individual and
      comorbid conditions as well as conditions that are described as limiting
      activity. STUDY DESIGN AND SETTING: Data were collected through online and clinic
      recruitment as part of the PROMIS item calibration sample (n=21,133).
      Participants reported the presence or absence of 24 chronic health conditions and
      whether their activity was limited by each condition. RESULTS: Across health
      status domains, the presence of a chronic condition was associated with poorer
      scores than those without a diagnosis, particularly for those individuals who
      reported that their condition was disabling. The magnitude of detriment in HRQL
      was more pronounced for individuals with two or more chronic conditions and could
      not be explained by sociodemographic factors. Patterns of HRQL deficits varied
      across disease and comorbidity status. CONCLUSION: The impact of chronic
      conditions, particularly when experienced with comorbid disease, is associated
      with detriments in HRQL. The negative impact on HRQL varies across symptoms and
      functional areas within a given condition.

PMID- 20688472
TI  - Graphical methods and numerical summaries for presenting results from multiple
      treatment meta-analysis: an overview and tutorial.
AB  - OBJECTIVE: To present some simple graphical and quantitative ways to assist
      interpretation and improve presentation of results from multiple-treatment meta
      analysis (MTM). STUDY DESIGN AND SETTING: We reanalyze a published network of
      trials comparing various antiplatelet interventions regarding the incidence of
      serious vascular events using Bayesian approaches for random effects MTM, and we
      explore the advantages and drawbacks of various traditional and new forms of
      quantitative displays and graphical presentations of results. RESULTS: We present
      the results under various forms, conventionally based on the mean of the
      distribution of the effect sizes; based on predictions; based on ranking
      probabilities; and finally, based on probabilities to be within an acceptable
      range from a reference. We show how to obtain and present results on ranking of
      all treatments and how to appraise the overall ranks. CONCLUSIONS: Bayesian
      methodology offers a multitude of ways to present results from MTM models, as it
      enables a natural and easy estimation of all measures based on probabilities,
      ranks, or predictions.

PMID- 20688473
TI  - Representativeness of the Patient-Reported Outcomes Measurement Information
      System Internet panel.
AB  - OBJECTIVES: To evaluate the Patient-Reported Outcomes Measurement Information
      System (PROMIS), which collected data from an Internet polling panel, and to
      compare PROMIS with national norms. STUDY DESIGN AND SETTING: We compared
      demographics and self-rated health of the PROMIS general Internet sample
      (N=11,796) and one of its subsamples (n=2,196) selected to approximate the joint
      distribution of demographics from the 2000 U.S. Census, with three national
      surveys and U.S. Census data. The comparisons were conducted using equivalence
      testing with weights created for PROMIS by raking. RESULTS: The weighted PROMIS
      population and subsample had similar demographics compared with the 2000 U.S.
      Census, except that the subsample had a higher percentage of people with higher
      education than high school. Equivalence testing shows similarity between PROMIS
      general population and national norms with regard to body mass index, EQ-5D
      health index (EuroQol group defined descriptive system of health-related quality
      of life states consisting of five dimensions including mobility, self-care, usual
      activities, pain/discomfort, anxiety/depression), and self-rating of general
      health. CONCLUSION: Self-rated health of the PROMIS general population is similar
      to that of existing samples from the general U.S. population. The weighted PROMIS
      general population is more comparable to national norms than the unweighted
      population with regard to subject characteristics. The findings suggest that the
      representativeness of the Internet data is comparable to those from probability
      based general population samples.

PMID- 20688474
TI  - Vitamin C provision improves mood in acutely hospitalized patients.
AB  - OBJECTIVE: Hypovitaminosis C and D are highly prevalent in acutely hospitalized
      patients, but the clinical significance of these biochemical abnormalities is not
      known. Because deficiencies of vitamin C and D have been linked to psychologic
      abnormalities, vitamin C or D provision could improve the mood state of acutely
      hospitalized patients. METHODS: Double-blind clinical trial of the effect of
      vitamin C (500 mg twice daily) or vitamin D (1000 IU twice daily) on mood, as
      assessed with a validated instrument, the Profile of Mood States. RESULTS:
      Vitamin C therapy increased plasma (P < 0.0001) and mononuclear leukocyte (P =
      0.014) vitamin C concentrations and was associated with a 34% reduction in mood
      disturbance (P = 0.013). Vitamin D therapy increased plasma 25-hydroxyvitamin D
      concentrations (P = 0.0004), but had no significant effect on mood. CONCLUSIONS:
      Treatment of hypovitaminosis C improves the mood state of acutely hospitalized
      patients.

PMID- 20688475
TI  - Dietary diversity and adequacy of women caregivers in a peri-urban informal
      settlement in South Africa.
AB  - OBJECTIVE: Simple measures reflecting dietary quality are preferred for
      assessment of dietary intakes in low-income communities, e.g. dietary diversity
      that reflects a healthy, varied, nutritious diet, associated with nutrient
      adequacy. A strong association between household income and food access suggests
      dietary diversity assessment as one of the indicators of household food security.
      The aim of this study was to assess the food security situation of black women in
      an informal settlement by exploring their food access capabilities through
      dietary diversity measures and the coping strategies they employ to cope with
      poverty and hunger. METHODS: A randomly selected sample of black women living in
      an informal settlement completed a pretested socio-demographic questionnaire
      (socio-economic circumstances) and validated questionnaires (1-wk quantified food
      frequency questionnaire: diversity measures; 24-h recall: nutrient intake;
      Cornell Hunger Scale: coping strategies). Food variety scores and food group
      diversity scores were calculated from frequency analyses for all foods and food
      groups. Nutrient adequacy ratios for various nutrients and the mean adequacy
      ratio for their diet were calculated. Relationships between dietary diversity and
      nutritional adequacy were investigated with Pearson correlations. Food variety
      score cut points were tested for sensitivity and specificity against nutritional
      adequacy. RESULTS: Intakes were deficient for all nutrients except carbohydrates.
      Individual mean +/- SD nutrient adequacy ratios ranging between 0.15 +/- 0.18 and
      0.95 +/- 0.19 confirmed the poor dietary quality. Zero to 40 individual foods
      were consumed, but the mean +/- SD food variety score was only 3.17 +/- 1.21,
      indicating low food diversity, as did the low dietary diversity score (2.82 +/-
      0.99) using 0 to 6 food groups. CONCLUSIONS: Limited food access and food variety
      in poor households resulted in inadequate nutrient intakes (low nutrient adequacy
      ratios), confirmed by poor dietary diversity (food variety score and food group
      diversity score). Dietary diversity assessment can successfully replace
      traditional dietary assessment tools in poverty-stricken or low-income
      communities where quick assessments are often required to assess the greatest
      need.

PMID- 20688476
TI  - Iron intake, red cell indicators of iron status, and DNA damage in young
      subjects.
AB  - OBJECTIVE: This study evaluated the association between primary DNA damage and
      chromosomal damage with iron intake and red blood cell parameters of iron status
      in a sample of healthy children and adolescents from a low-socioeconomic
      community. METHODS: The level of primary DNA damage was assessed using an
      alkaline comet assay and the level of chromosomal damage was assessed using the
      cytokinesis-block micronucleus assay. A automated complete blood count was used
      to evaluate red blood cell status. The intake of iron was measured using a food
      recall questionnaire. RESULTS: According to hemoglobin levels, only 1 of the 30
      subjects evaluated was anemic. Nevertheless, 43% of the sampled subjects showed
      decreased mean corpuscular volume in addition to an increased amount of primary
      DNA damage (P < 0.05). Mean corpuscular volume was negatively correlated with
      primary DNA damage (r = -0.429, P = 0.020) but not with chromosomal damage. The
      association between iron and primary DNA damage showed a U-shaped curve,
      indicating that an intake of approximately 15 mg of iron per day (up to two-fold
      of the dietary recommended intake) could minimize primary DNA damage in this age
      group. The frequency of micronuclei and nucleoplasmic bridges, indicators of
      chromosomal breakage/loss and chromosomal end-fusions, respectively, showed a
      negative correlation with iron intake. These results indicate that an intake of
      iron >15 mg/d could increase genomic stability in binucleated lymphocytes of the
      same group. CONCLUSION: An intake of iron >= 15 mg/d can decrease DNA damage in
      young subjects.

PMID- 20688477
TI  - Wedge subcoronoid ostectomy: an alternative to coronoidotomy.
AB  - While coronoidotomy and coronoidectomy remain established procedures in
      maxillofacial surgery, exceptionally enlarged coronoids pose a special challenge,
      as their intraoral retrieval may be difficult or impossible. Classical
      coronoidotomy alone in such situations may risk reattachment and recurrence of
      trismus. The technique described allows creation of sufficient gap and
      interpositioning at the coronoid base, allowing achievement of satisfactory mouth
      opening while minimising the risk for reattachment and relapse.

PMID- 20688478
TI  - WITHDRAWN: Cell alterations and molecular mechanisms in oral carcinogenesis.
AB  - This article has been withdrawn at the request of the author(s) and/or 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- 20688479
TI  - Spatial working memory in individuals at high risk for psychosis: longitudinal
      fMRI study.
AB  - BACKGROUND: Neurocognitive impairments in executive and mnemonic domains are
      already evident in the pre-psychotic phases. The longitudinal dynamic course of
      the neurofunctional abnormalities underlying liability to psychosis and their
      relation to clinical outcomes is unknown. METHODS: In this study we used
      functional magnetic resonance imaging (fMRI) in a cohort of subjects at ultra
      high clinical risk for psychosis (with an "At Risk Mental State", ARMS) and in
      healthy controls. Images were acquired at baseline and again after one year on a
      1.5 Tesla Signa, while patients were performing a visuospatial working memory
      task. Psychopathological assessment of the prodromal symptoms was conducted at
      the same time points by using the CAARMS and the PANSS instruments. RESULTS:
      There were no significant differences between the ARMS and control groups with
      respect to age or IQ. Although both groups performed the PAL task with a high
      degree of accuracy, the ARMS showed an increased latency in answers during the
      most demanding level of the task. At baseline, such cognitive impairment was
      associated with reduced activation in the left precuneus, left superior parietal
      lobule, right middle temporal gyrus in the ARMS as compared to controls. In
      addition, the ARMS failed to activate parietal areas with increasing difficulty
      of the task. Between presentation and follow-up the overall clinical status of
      the ARMS sample improved, despite 2 out of the 15 subjects having developed a
      full-blown psychosis: the CAARMS (perceptual disorder and thought disorder
      subscales) and the PANNS general scores decreased, while the GAF score increased.
      Such clinical amelioration was associated with a longitudinal compensatory
      increase in occipitoparietal regions. CONCLUSIONS: The prodromal phase of
      psychosis is associated with functional alterations in parietal and temporal
      networks subserving visuospatial working memory which are more evident under high
      cognitive loads. The clinical improvement at one year is associated with a
      compensatory increase in occipitoparietal regions.

PMID- 20688481
TI  - Long-acting injectable risperidone in treatment refractory patients: a 14-week
      open-label pilot study.

PMID- 20688482
TI  - A novel mutation in the kinase domain of KIT in an Indian family with a mild
      piebaldism phenotype.

PMID- 20688483
TI  - Epimorphin-derived peptide antagonists remedy epidermal parakeratosis triggered
      by unsaturated fatty acid.
AB  - BACKGROUND: Unsaturated fatty acid from accumulated sebum disrupts calcium influx
      in keratinocytes and triggers epidermal hyperplasia, leading to comedone
      formation in the skin. Oleic acid, a representative unsaturated fatty acid, has
      been shown to be a useful reagent to induce these cellular alternations, however,
      the detailed mechanism still remains to be elucidated. OBJECTIVES: This study
      aimed at the identification of the mediator of unsaturated fatty acid-caused
      epidermal hyperplasia so as to generate the effective therapeutic agents.
      METHODS: The downstream mediator of oleic acid-treatment was identified in the
      epidermal keratinocyte and the effect of its antagonistic peptides on the
      epidermal behaviors was investigated in culture and in vivo. RESULTS: In culture,
      treatment with oleic acid augmented extracellular secretion of epimorphin in
      HaCaT keratinocytes and prevented the epidermal terminal differentiation
      including programmed cell death and cornified envelope formation. The
      antagonistic peptide of epimorphin (EPn1: a circular compound composed of
      CGSIEQSC), which was newly generated in this study, restored normal keratinocyte
      behaviors. In hairless mice, topical application of oleic acid to the dorsal skin
      caused epidermal hyperplasia with decreased enucleation in the horny layer, which
      was dramatically hampered by the administration of EPn1. CONCLUSIONS: The effects
      of unsaturated fatty acid are attributed to the overstimulation of epimorphin
      signaling and suggest the epimorphin antagonist as a possible therapeutic agent
      for acne and hyperkeratotic skin disease.

PMID- 20688484
TI  - Estimating the burden of human leptospirosis.
AB  - Leptospirosis, a disease that is often under- or misdiagnosed, significantly
      impacts human health in many parts of the world and generally affects the most
      vulnerable communities. Obtaining reliable and comparable information about the
      occurrence of leptospirosis in populations, and detecting changing trends, are
      critical for setting policy and public health priorities. Traditional sources of
      information about the descriptive epidemiology, the disability attributed to
      leptospirosis infection, and associated risk factors are generally incomplete,
      fragmented and of uncertain reliability and comparability. Therefore, the global
      burden of disease concept and methodological framework will be used by the World
      Health Organization's (WHO) initiative to estimate the global burden of human
      leptospirosis. The aim of the initiative is to quantify and compare the health of
      populations by a summary measure of both mortality and disability, the disability
      adjusted life year (DALY). WHO has established the Leptospirosis Burden
      Epidemiology Reference Group (LERG) to coordinate the assessment. The burden
      estimates provided by the LERG will guide public health policy on leptospirosis
      disease control and prevention, with the aim of reducing the impact on human
      health.

PMID- 20688485
TI  - Genotypic analysis of plasmid-mediated beta-lactamases amongst Enterobacteriaceae
      other than Escherichia spp. and Klebsiella spp. that are non-susceptible to a
      broad-spectrum cephalosporin.
AB  - Enterobacteriaceae other than Escherichia spp. and Klebsiella spp. are
      recognisable for their increasing resistance. Plasmid-mediated beta-lactamases,
      including extended-spectrum beta-lactamases (ESBLs), plasmid-mediated AmpC beta
      lactamases (pAmpCs) and the newly emerged KPC, play an important role in beta
      lactam resistance. In this study, we investigated the genetic characteristics of
      plasmid-mediated beta-lactamases amongst non-Escherichia, non-Klebsiella
      Enterobacteriaceae that were non-susceptible to at least a broad-spectrum
      cephalosporin. A total of 143 (23.9%) of 598 isolates during the 6-month study
      period met the screening criteria, amongst which 142 (99.3%) and 99 (69.2%)
      isolates carried ESBL and pAmpC genes, respectively. Resistance genotypes were
      described. bla(KPC) was not detected in isolates with reduced susceptibility to
      carbapenems. This study provides an insight into plasmid-mediated resistance
      determinants amongst cephalosporin-non-susceptible Enterobacteriaceae other than
      Escherichia spp. and Klebsiella spp.

PMID- 20688486
TI  - Impact of restricted amoxicillin/clavulanic acid use on Escherichia coli
      resistance--antibiotic DU90% profiles with bacterial resistance rates: a visual
      presentation.
AB  - High use of amoxicillin/clavulanic acid (AMC) at the University Hospital Osijek
      (Croatia) contributed to high rates of resistance in Enterobacteriaceae, in
      particular Escherichia coli (50%). Thus, in order to decrease bacterial
      resistance, AMC use was restricted. We present results of the restriction on
      resistance amongst antibiotics accounting for 90% of antibiotic use [drug
      utilisation 90% (DU90%)]. Data were analysed on antibiotic use and
      microbiological susceptibility of E. coli during two 9-month periods, before and
      after the restriction of AMC use. Drug use was presented as numbers of defined
      daily doses (DDDs) and DDDs/100 bed-days. Resistance of E. coli to antibiotics
      was presented as percentages of isolated strains in the DU90% segment. Use of AMC
      was 16 DDDs/100 bed-days or 30% of all antibiotics before the intervention. Use
      of AMC fell to 2 DDDs/100 bed-days or 4% after the intervention, and resistance
      of E. coli fell from 37% to 11%. In conclusion, restricted use of AMC resulted in
      a significant decrease of E. coli resistance. DU90% resistance profiles are
      simple and useful tools in highlighting problems in antibiotic use and resistance
      but may also be useful in long-term follow-up of antibiotic policy.

PMID- 20688487
TI  - Physiological characterisation of the efflux pump system of antibiotic
      susceptible and multidrug-resistant Enterobacter aerogenes.
AB  - Enterobacter aerogenes predominates amongst Enterobacteriaceae species that are
      increasingly reported as producers of extended-spectrum beta-lactamases. Although
      this mechanism of resistance to beta-lactams is important, other mechanisms
      bestowing a multidrug-resistant (MDR) phenotype in this species are now well
      documented. Amongst these mechanisms is the overexpression of efflux pumps that
      extrude structurally unrelated antibiotics prior to their reaching their targets.
      Interestingly, although knowledge of the genetic background behind efflux pumps
      is rapidly advancing, few studies assess the physiological nature of the overall
      efflux pump system of this, or for that matter any other, bacterium. The study
      reported here evaluates physiologically the efflux pump system of an E. aerogenes
      ATCC reference as well as two strains whose MDR phenotypes are mediated by
      overexpressed efflux pumps. The activities of the efflux pumps in these strains
      are modulated by pH and glucose, although the effects of the latter are
      essentially restricted to pH 8, suggesting the presence of two general efflux
      pump systems, i.e. proton-motive force-dependent and ABC transporter types,
      respectively.

PMID- 20688488
TI  - Preserved subcortical volumes and cortical thickness in women with sexual abuse
      related PTSD.
AB  - Posttraumatic stress disorder (PTSD) has been frequently associated with
      volumetric reductions of grey matter structures (e.g. hippocampus and anterior
      cingulate), but these results remain controversial, especially in female non
      combat-related samples. The present study aimed at exploring whole-brain
      structures in women with sexual abuse-related PTSD on the basis of cortical and
      subcortical structure comparisons to a matched pair sample that was well
      controlled. Seventeen young women who had experienced sexual abuse and who had a
      diagnosis of chronic PTSD based on the Clinician Administered PTSD Scale for DSM
      IV and 17 healthy controls individually matched for age and years of education
      were consecutively recruited. Both groups underwent structural magnetic resonance
      imaging and psychiatric assessment of the main disorders according to Axis I of
      DSM-IV. The resulting scans were analyzed using automated cortical and
      subcortical volumetric quantifications. Compared with controls, PTSD subjects
      displayed normal global and regional brain volumes and cortical thicknesses. Our
      results indicate preserved subcortical volumes and cortical thickness in a sample
      of female survivors of sexual abuse with PTSD. The authors discuss potential
      differences between neural mechanisms of sexual abuse-related PTSD and war
      related PTSD.

PMID- 20688489
TI  - Desktop fast-field cycling nuclear magnetic resonance relaxometer.
AB  - In this paper a new type of Fast Field Cycling (FFC) Nuclear Magnetic Resonance
      (NMR) relaxometer with low power consumption (200W) and cycle to cycle field
      stability better than 10(-4) is described. The new high-permeability magnet was
      designed to allow for good magnetic field homogeneity and allows for the sample
      rotation around an axis perpendicular to magnetic field, operating with magnetic
      fields between 0 and 0.21T. The power supply of the new relaxometer was specially
      developed in order to have steady state accurate currents and allow for magnetic
      field switching times less than 3ms. Additional control circuits were developed
      and included to compensate the Earth magnetic field component parallel to the
      field axis and to compensate for parasitic currents. The main aspects of the
      developed circuits together with some calibrating experimental results using the
      liquid crystal compounds 5CB and 8CB are presented and discussed.

PMID- 20688490
TI  - Rhamnolipid mediated disruption of marine Bacillus pumilus biofilms.
AB  - Removal of detrimental biofilms from surfaces exposed in the marine environment
      remains a challenge. A strain of Bacillus pumilus was isolated from the surface
      of titanium coupons immersed in seawater in the vicinity of Madras Atomic Power
      Station (MAPS) on the East coast of India. The bacterium formed extensive
      biofilms when compared to species such as Bacillus licheniformis, Pseudomonas
      aeruginosa PAO1 and Pseudomonas aureofaciens. A commercially available
      rhamnolipid was assessed for its ability to inhibit adhesion and disrupt pre
      formed B. pumilus biofilms. The planktonic growth of B. pumilus cells was
      inhibited by concentrations >1.6mM. We studied the effect of various
      concentrations (0.05-100mM) of the rhamnolipid on adhesion of B. pumilus cells to
      polystyrene microtitre plates, wherein the effectiveness varied from 46 to 99%.
      Biofilms of B. pumilus were dislodged efficiently at sub-MIC concentrations,
      suggesting the role of surfactant activity in removing pre-formed biofilms.
      Scanning electron microscopy (SEM) confirmed the removal of biofilm-matrix
      components and disruption of biofilms by treatment with the rhamnolipid. The
      results suggest the possible use of rhamnolipids as efficient anti-adhesive and
      biofilm-disrupting agents with potential applications in controlling biofilms on
      surfaces.

PMID- 20688491
TI  - Microcapsules of alginate/chitosan containing magnetic nanoparticles for
      controlled release of insulin.
AB  - The challenge of this work was to investigate the potential of alginate/chitosan
      beads containing magnetite nanoparticles as a drug delivery system. The insulin
      beads were prepared by dripping a solution of sodium alginate containing insulin
      into a CaCl(2) solution. Magnetite nanoparticles of 5 nm mean size were
      synthesized inside the alginate egg-box structure by co-precipitation of Fe(III)
      and Fe(II) in the presence of NH(4)OH. Quantitative analysis revealed that
      insulin encapsulation depends on the initial protein content and 35% of insulin
      was entrapped by alginate beads for a protein concentration of 10 wt%. It was
      verified that approximately 50% of the insulin was released to Milli-Q water in
      800 h release experiments. The application of oscillating magnetic field
      increased three fold the insulin release. The results suggest that the
      alginate/chitosan system containing magnetite nanoparticles is a promising system
      for clinical applications of controlled release of insulin in the presence of an
      oscillating magnetic field in a subcutaneous implant approach.

PMID- 20688492
TI  - Preparation of 2-mercaptobenzothiazole-labeled immuno-Au aggregates for SERS
      based immunoassay.
AB  - A detailed method for preparation of 2-mercaptobenzothiazole (MBT)-labeled immuno
      Au aggregates as a novel Raman probe for SERS-based immunoassay has been proposed
      in this paper. The formation kinetics of gold aggregates induced by MBT and the
      impact of the amount of labeled reporter on the aggregation, as well as the
      fabrication of MBT-labeled immuno-Au aggregates were characterized
      comprehensively by UV-vis spectrophotometer. Meanwhile, a chain-like morphology
      of aggregates was monitored by TEM images. Experimental results show that this
      Raman tag can act as an efficient label and an enhanced Raman signal of SERS
      based immunoassay can be obtained successfully with this novel probe. This work
      shows the method for the preparation of immune probe for SERS-based immunoassay
      using MBT as reporter and provides a reference for the preparation of immune
      probe with other Raman markers for multi-channel SERS-based immunoassay.

PMID- 20688494
TI  - Clinical application of image-guided radiotherapy in bladder and prostate cancer.
AB  - Advances in radiotherapy planning reduced the volumes of irradiated normal tissue
      and allowed safe dose escalation in prostate cancer. Image-guided radiotherapy
      solutions to prostate and bladder cancer offer further improvements. The initial
      process is understanding the causes and extent of internal organ motion, followed
      by development of equipment and protocols to minimise geographical miss. Further
      refinements may allow margin reduction and further dose escalation. This paper
      reviews these issues for bladder and prostate cancer.

PMID- 20688493
TI  - Curcuminoids-loaded lipid nanoparticles: novel approach towards malaria
      treatment.
AB  - In the present work, curcuminoids-loaded lipid nanoparticles for parenteral
      administration were successfully prepared by a nanoemulsion technique employing
      high-speed homogenizer and ultrasonic probe. For the production of nanoparticles,
      trimyristin, tristerin and glyceryl monostearate were selected as solid lipids
      and medium chain triglyceride (MCT) as liquid lipid. Scanning electron microscopy
      (SEM) revealed the spherical nature of the particles with sizes ranging between
      120 and 250 nm measured by photon correlation spectroscopy (PCS). The zeta
      potential of the particles ranged between -28 and -45 mV depending on the nature
      of the lipid matrix produced, which also influenced the entrapment efficiency
      (EE) and drug loading capacity (LC) found to be in the range of 80-94% and 1.62
      3.27%, respectively. The LC increased reciprocally on increasing the amount of
      MCT as confirmed by differential scanning calorimetry (DSC). DSC analyses
      revealed that increasing imperfections within the lipid matrix allowed for
      increasing encapsulation parameters. Nanoparticles were further sterilized by
      filtration process which was found to be superior over autoclaving in preventing
      thermal degradation of thermo-sensitive curcuminoids. The in vivo pharmacodynamic
      activity revealed 2-fold increase in antimalarial activity of curcuminoids
      entrapped in lipid nanoparticles when compared to free curcuminoids at the tested
      dosage level.

PMID- 20688495
TI  - Therapeutic potential of N-acetyl cysteine with antioxidants (Zn and Se)
      supplementation against dimethylmercury toxicity in male albino rats.
AB  - Mercury (Hg) is currently one of the most prevalent pollutants in the
      environment. Many studies have examined its effects on the health of both humans
      and animals. Experimental studies have shown that sulfur-containing nutrients
      play an important role as detoxification and protecting cell against the
      detrimental properties of mercury. The present study was undertaken to elucidate
      the toxicity induced by dimethylmercury in male rats through the activities of
      transaminases, alkaline phosphatase, lactate dehydrogenase in serum and oxidative
      damage as acetyl cholinesterase activity in different regions of brain and lipid
      peroxidation, reduced glutathione content, mean DNA damage in liver, kidney and
      brain of rats given dimethylmercury (10 mg/kg, p.o., once only) along with
      combination therapy of N-acetyl cysteine (2 mM/kg, i.p.), zinc (2 mM/kg, p.o.)
      and selenium (0.5 mg/kg, p.o.) for 3 days. In the dimethylmercury group,
      activities of transaminases, alkaline phosphatase, lactate dehydrogenase in
      serum, level of lipid peroxidation, mean DNA damage and mercury ion concentration
      were significantly higher whereas reduced glutathione content and the activity of
      acetyl cholinesterase were significantly lower compared to controls (P<=0.05).
      Combined treatment of zinc and selenium with N-acetyl cysteine to dimethylmercury
      exposed rats showed a substantial reduction in the levels of DMM-induced
      oxidative damage and comet tail length. In conclusion, the results of this study
      support that the supplementation of zinc and selenium with N-acetyl cysteine can
      improve the DMM induced blood and tissue biochemical oxidative stress and
      molecular alterations by recoupment in mean DNA damage.

PMID- 20688496
TI  - Histopathological features of the brain, liver, kidney and spleen following an
      innovative polytrauma model of the mouse.
AB  - OBJECT: Among the various introduced experimental traumatic brain injury models,
      there is a clear paucity of proper experimental polytrauma models. To overcome
      this experimental gap we introduced such a polytrauma model in the mouse
      including traumatic brain injury. Here, we report on the histopathological
      features of the brain, lung, kidney, spleen and liver. MATERIALS AND METHODS: 20
      male C57BL mice with a mean weight of 23 g were anesthetized with ketamine and
      xylazine. The anaesthetized animals were subjected to a controlled cortical
      impact (CCI) over the left parieto-temporal cortex using rounded-tip impounder
      for application of a standardized brain injury. Following fracture of the right
      femur using a guillotine, a volume-controlled hemorrhagic shock was induced. The
      control groups included animals with CCI only (n=20) and animals with femur
      fracture plus hemorrhagic shock without CCI (n=20). Subjects were sacrified at 96
      h following trauma. Brain, lung, kidney, spleen and liver of the animals
      underwent histopathological examinations. RESULTS: The mortality rate at 96 h was
      25% in the polytrauma group versus 10% in the control groups. Within the
      histopathological investigations, polytraumatized animals differ from those with
      a single trauma (traumatic brain injury or femur fracture with hemorrhagic shock)
      with various severity. CONCLUSION: The findings of this study show that such a
      polytrauma model can be standardized resulting in a reproducible damage. This
      model fulfills the requirements of a standardized animal model. It allows
      adequate analogies and inferences to the clinical situation of a polytrauma in
      humans.

PMID- 20688497
TI  - Enhancement of antibody synthesis in rats by feeding cis-9,trans-11 conjugated
      linoleic acid during early life.
AB  - Previous studies have demonstrated that the intake of a 1% conjugated linoleic
      acid (CLA) diet in an 80:20 mixture of cis-9,trans-11 and trans-10,cis-12 exerts
      age-specific effects on the immune system: immunoglobulin enhancement and
      proliferative down-modulation in neonatal and adult rats, respectively. The
      present study evaluates the influence of the same diet on antibody synthesis of
      early infant Wistar rats during suckling and/or after weaning. Dietary
      supplementation was performed during suckling and early infancy (4 weeks), only
      during suckling (3 weeks), or only in early infancy (1 week). CLA content in
      plasma and serum immunoglobulin (Ig) G, IgM and IgA concentration were
      determined. Proliferation, cytokines and Ig production were evaluated on isolated
      splenocytes. Cis-9,trans-11- and trans-10,cis-12-CLA isomers were detected in the
      plasma of all CLA-supplemented animals, and the highest content was quantified in
      those rats supplemented over the longest period. These rats also exhibited higher
      concentrations of serum IgG, IgM and IgA. Moreover, splenocytes from CLA
      supplemented rats showed the highest IgM and IgG synthesis and interleukin (IL)-6
      production, whereas their proliferative ability was lower. In summary, in infant
      rats, we observed both the enhance antibody synthesis previously reported in
      neonates, and the reduced lymphoproliferation previously reported in adults.

PMID- 20688498
TI  - Saturated fat intake and alcohol consumption modulate the association between the
      APOE polymorphism and risk of future coronary heart disease: a nested case
      control study in the Spanish EPIC cohort.
AB  - The association is still not clear between the common APOE polymorphism and
      coronary heart disease (CHD) risk, nor its modulation by diet. Thus, our aim was
      to study the association between the APOE genotypes and incident CHD and how
      dietary fat and alcohol consumption modify these effects. We performed a nested
      case-control study in the Spanish European Prospective Investigation into Cancer
      and Nutrition cohort. Healthy men and women (41,440, 30-69 years) were followed
      up over a 10-year period, with the incident CHD cases being identified. We
      analyzed 534 incident CHD cases and 1123 controls. APOE, dietary intake and
      plasma lipids were determined at baseline. The APOE polymorphism was
      significantly associated with low-density lipoprotein cholesterol (LDL-C), and
      gene-alcohol interactions in determining LDL-C were detected. In the whole
      population, the E2 allele was significantly associated with a lower CHD risk than
      E3/E3 subjects [odds ratio (OR), 0.58; 95% confidence interval (CI), 0.38-0.89].
      The E4 allele did not reach statistical significance vs. E3/E3 (OR, 1.17; 95% CI,
      0.88-1.58). However, saturated fat intake modified the effect of the APOE
      polymorphism in determining CHD risk. When saturated fat intake was low (<10% of
      energy), no statistically significant association between the APOE polymorphism
      and CHD risk was observed (P=.682). However, with higher intake (>=10%), the
      polymorphism was significant (P=.005), and the differences between E2 and E4
      carriers were magnified (OR for E4 vs. E2, 3.33; 95% CI, 1.61-6.90). Alcohol
      consumption also modified the effect of the APOE on CHD risk. In conclusion, in
      this Mediterranean population, the E2 allele is associated with lower CHD risk,
      and this association is modulated by saturated fat and alcohol consumption.

PMID- 20688499
TI  - Clock genes regulate the feeding schedule-dependent diurnal rhythm changes in
      hexose transporter gene expressions through the binding of BMAL1 to the
      promoter/enhancer and transcribed regions.
AB  - The expression of hexose transporter genes (SGLT1, GLUT5 and GLUT2) in mice with
      ad libitum feeding under light (7:00-19:00)-dark (19:00-7:00) cycle gradually
      increased from a basal level at 7:00 and reached a maximum at 19:00, coinciding
      with the start of dark phase feeding. The peaks of these gene expressions were
      shifted to 7:00 in mice that were subjected to a restricted feeding schedule from
      9:00 to 17:00. The expression of BMAL1, a transcription factor driving the
      central feedback loop of the clock genes, was followed by the increase of hexose
      transporter gene expressions. The expressions of Per1-3, genes related to
      negative regulation of BMAL1, were the highest at or just after the time of
      maximal expression of the hexose transporter genes in both the group fed ad
      libitum and the restricted feeding group. Furthermore, chromatin
      immunoprecipitation assays revealed that the binding of BMAL1 to the promoter
      and/or transcribed regions of hexose transporters and Per 2 genes was associated
      with changes in their expressions. These results suggest that diurnal changes in
      expression of hexose transporter genes depend on the feeding schedule and are
      directly regulated by a feedback loop of clock genes.

PMID- 20688500
TI  - Holocarboxylase synthetase is a chromatin protein and interacts directly with
      histone H3 to mediate biotinylation of K9 and K18.
AB  - Holocarboxylase synthetase (HCS) mediates the binding of biotin to lysine (K)
      residues in histones H2A, H3 and H4; HCS knockdown disturbs gene regulation and
      decreases stress resistance and lifespan in eukaryotes. We tested the hypothesis
      that HCS interacts physically with histone H3 for subsequent biotinylation. Co
      immunoprecipitation experiments were conducted and provided evidence that HCS co
      localizes with histone H3 in human cells; physical interactions between HCS and
      H3 were confirmed using limited proteolysis assays. Yeast two-hybrid (Y2H)
      studies revealed that the N-terminal and C-terminal domains in HCS participate in
      H3 binding. Recombinant human HCS was produced and exhibited biological activity,
      as evidenced by biotinylation of its known substrate, recombinant p67.
      Recombinant histone H3.2 and synthetic H3-based peptides were also good targets
      for biotinylation by recombinant HCS (rHCS) in vitro, based on tracing histone
      bound biotin with [(3)H]biotin, streptavidin and anti-biotin antibody.
      Biotinylation site-specific antibodies were generated and revealed that both K9
      and K18 in H3 were biotinylated by HCS. Collectively, these studies provide
      conclusive evidence that HCS interacts directly with histone H3, causing
      biotinylation of K9 and K18. We speculate that the targeting of HCS to distinct
      regions in human chromatin is mediated by DNA sequence, biotin, RNA, epigenetic
      marks or chromatin proteins.

PMID- 20688501
TI  - 4-O-methylhonokiol attenuated beta-amyloid-induced memory impairment through
      reduction of oxidative damages via inactivation of p38 MAP kinase.
AB  - Oxidative stress induced neuronal cell death by accumulation of beta-amyloid
      (Abeta) is a critical pathological mechanism of Alzheimer's disease (AD).
      Intracerebroventrical infusion of Abeta(1-42) (300 pmol/day per mouse) for 14
      days induced neuronal cell death and memory impairment, but pre-treatment of 4-O
      methylhonokiol (4-O-MH), a novel compound extracted from Magnolia officinalis for
      3 weeks (0.2, 0.5 and 1.0 mg/kg) prior to the infusion of Abeta(1-42) and during
      the infusion dose dependently improved Abeta(1-42)-induced memory impairment and
      prevented neuronal cell death. Additionally, 4-O-MH reduced Abeta(1-42) infusion
      induced oxidative damages of protein and lipid but reduced glutathione levels in
      the cortex and hippocampus. Abeta(1-42) infusion-induced activation of astrocytes
      and p38 mitogenic activated protein (MAP) kinase was also prevented by 4-O-MH in
      mice brains. In further study using culture cortical neurons, p38 MAP kinase
      inhibitor abolished the inhibitory effect of 4-O-MH (10 MUM) on the Abeta(1-42)
      (5 MUM)-induced reactive oxidative species generation and neuronal cell death.
      These results suggest that 4-O-MH might prevent the development and progression
      of AD through the reduction of oxidative stress and neuronal cell death via
      inactivation of p38 MAP kinase pathway.

PMID- 20688502
TI  - Critical care management of patients before liver transplantation.
AB  - The critical care management of patients before liver transplantation is aimed at
      optimizing hepatic and extrahepatic organ function before the transplant
      operation, with a goal to favorably influence perioperative and postoperative
      graft and patient outcomes. Critical illness in liver disease can present in the
      context of acute liver failure or acute on chronic liver failure. The differing
      pathophysiologic processes underlying these 2 types of liver failure necessitate
      specific approaches to their intensive care management. In their extreme
      presentations, both types of liver failure present as multiorgan system failure;
      and therefore, the critical care management of these entities requires a
      systematic multiorgan system approach to address hepatic and extrahepatic organ
      dysfunction. This review provides a multiorgan system-based description of
      critical care management of acute liver failure and acute on chronic liver
      failure before liver transplantation.

PMID- 20688503
TI  - Influence of pine wood shavings on the pyrolysis of poultry litter.
AB  - Poultry litter from broilers and turkeys are a mixture of manure, feathers, feed
      and wood shavings, thus pyrolysis oils produced from this material are influenced
      by the individual components. In order to determine the influence of wood
      shavings that are used as bedding material, we investigated the pyrolysis of pine
      wood shavings and poultry manure. Because manure from layer chickens are usually
      not contaminated with wood shavings, we made mixtures of layer manure and pine
      wood shavings in the following manure to wood ratios, 100:0, 75:25, 50:50, 25:75,
      and 0:100 w/w and pyrolyzed them in a fluidized bed reactor at 450  degrees C.
      The total liquid yield ranged from 43.3 to 62.7 wt.%. The layer manure oil had a
      HHV of 29.7 MJ/kg and pH of 5.89 compared to pine wood oil which had HHV of 25.6
      MJ/kg and pH of 3.04. The addition of wood shavings to manure clearly influenced
      the physical properties of the oil, resulting in a decrease in pH and HHV and an
      increase in density. The oils had relatively high nitrogen content ranging from
      1.36 to 5.88 wt.%. The ash (<0.07 wt.%) and sulfur (<0.28 wt.%) contents were
      very low. FTIR, (13)C NMR and (1)H NMR spectrometric analysis of the oils showed
      that manure oil was rich in hydrocarbons and nitrogenous compounds such as
      primary, secondary amides, aromatic amines and N-heterocyclic. The properties of
      the oils were strongly influenced by the amount of wood in the mixture.

PMID- 20688504
TI  - Future trends in computer waste generation in India.
AB  - The objective of this paper is to estimate the future projection of computer
      waste in India and to subsequently analyze their flow at the end of their useful
      phase. For this purpose, the study utilizes the logistic model-based approach
      proposed by Yang and Williams to forecast future trends in computer waste. The
      model estimates future projection of computer penetration rate utilizing their
      first lifespan distribution and historical sales data. A bounding analysis on the
      future carrying capacity was simulated using the three parameter logistic curve.
      The observed obsolete generation quantities from the extrapolated penetration
      rates are then used to model the disposal phase. The results of the bounding
      analysis indicate that in the year 2020, around 41-152 million units of computers
      will become obsolete. The obsolete computer generation quantities are then used
      to estimate the End-of-Life outflows by utilizing a time-series multiple lifespan
      model. Even a conservative estimate of the future recycling capacity of PCs will
      reach upwards of 30 million units during 2025. Apparently, more than 150 million
      units could be potentially recycled in the upper bound case. However, considering
      significant future investment in the e-waste recycling sector from all
      stakeholders in India, we propose a logistic growth in the recycling rate and
      estimate the requirement of recycling capacity between 60 and 400 million units
      for the lower and upper bound case during 2025. Finally, we compare the future
      obsolete PC generation amount of the US and India.

PMID- 20688505
TI  - Direct detection of Salmonella typhimurium on fresh produce using phage-based
      magnetoelastic biosensors.
AB  - Current bacterial detection methods require the collection of samples followed by
      preparation and analysis in the laboratory, both time and labour consuming steps.
      More importantly, because of cost, only a limited number of samples can be taken
      and analyzed. This paper presents the results of an investigation to directly
      detect Salmonella typhimurium on fresh tomato surfaces using phage-based
      magnetoelastic (ME) biosensors. The biosensor is composed of a ME resonator
      platform coated with filamentous E2 phage, engineered to bind with S.
      typhimurium. The ME biosensors are wireless sensors, whose resonance oscillation
      and resonance frequency are actuated and detected through magnetic fields. The
      sensors used in this study were 0.028 mm*0.2 mm*1 mm in size. In this study, the
      tomato surface was spiked with S. typhimurium suspensions with concentrations
      ranging from 5*10(1) to 5*10(8)CFU/ml and then allowed to dry in air. The
      detection was conducted by directly placing ME measurement biosensors and control
      sensors on the spiked surface for 30 min in a humid environment. The control
      sensors were identical to the measurement biosensors, but without phage. Both
      measurement and control sensors were blocked with BSA to reduce non-specific
      binding. The resonance frequencies of both measurement and control sensors were
      measured prior to and after the placement of the sensors on the tomato. Shifts in
      the resonance frequency of the measurement biosensors were observed, while the
      control sensors showed negligible change. Scanning electron microscopy (SEM) was
      used to verify the specific binding of S. typhimurium to the biosensor. Results
      of multiple biosensor detection and corresponding analyzes showed statistically
      different responses between the measurement and control sensors for tomatoes
      spiked with S. typhimurium suspensions with concentrations of 5*10(2)CFU/ml and
      greater. This study demonstrates the direct detection of food-borne bacteria on
      fresh produce.

PMID- 20688506
TI  - Carbon nanotubes-based chemiresistive immunosensor for small molecules: detection
      of nitroaromatic explosives.
AB  - In recent years, there has been a growing focus on use of one-dimensional (1-D)
      nanostructures, such as carbon nanotubes and nanowires, as transducer elements
      for label-free chemiresistive/field-effect transistor biosensors as they provide
      label-free and high sensitivity detection. While research to-date has elucidated
      the power of carbon nanotubes- and other 1-D nanostructure-based field effect
      transistors immunosensors for large charged macromolecules such as proteins and
      viruses, their application to small uncharged or charged molecules has not been
      demonstrated. In this paper we report a single-walled carbon nanotubes (SWNTs)
      based chemiresistive immunosensor for label-free, rapid, sensitive and selective
      detection of 2,4,6-trinitrotoluene (TNT), a small molecule. The newly developed
      immunosensor employed a displacement mode/format in which SWNTs network forming
      conduction channel of the sensor was first modified with trinitrophenyl (TNP), an
      analog of TNT, and then ligated with the anti-TNP single chain antibody. Upon
      exposure to TNT or its derivatives the bound antibodies were displaced producing
      a large change, several folds higher than the noise, in the
      resistance/conductance of SWNTs giving excellent limit of detection, sensitivity
      and selectivity. The sensor detected between 0.5 ppb and 5000 ppb TNT with good
      selectivity to other nitroaromatic explosives and demonstrated good accuracy for
      monitoring TNT in untreated environmental water matrix. We believe this new
      displacement format can be easily generalized to other one-dimensional
      nanostructure-based chemiresistive immuno/affinity-sensors for detecting small
      and/or uncharged molecules of interest in environmental monitoring and health
      care.

PMID- 20688507
TI  - Man-tailored biomimetic sensor of molecularly imprinted materials for the
      potentiometric measurement of oxytetracycline.
AB  - A novel biomimetic sensor for the potentiometric transduction of oxytetracycline
      is presented. The artificial host was imprinted in methacrylic acid and/or
      acrylamide based polymers. Different amounts of molecularly imprinted and non
      imprinted polymers were dispersed in different plasticizing solvents and
      entrapped in a poly(vinyl chloride) matrix. Only molecularly imprinted based
      sensors allowed a potentiometric transduction, suggesting the existence of host
      guest interactions. These sensors exhibited a near-Nernstian response in steady
      state evaluations; slopes and detection limits ranged 42-63 mV/decade and 2.5
      31.3 MUg/mL, respectively. Sensors were independent from the pH of test solutions
      within 2-5. Good selectivity was observed towards glycine, ciprofloxacin,
      creatinine, acid nalidixic, sulfadiazine, cysteine, hydroxylamine and lactose. In
      flowing media, the biomimetic sensors presented good reproducibility (RSD of +/
      0.7%), fast response, good sensitivity (65 mV/decade), wide linear range (5.0*10(
      5) to 1.0*10(-2) mol/L), low detection limit (19.8 MUg/mL), and a stable baseline
      for a 5*10(-3) M citrate buffer (pH 2.5) carrier. The sensors were successfully
      applied to the analysis of drugs and urine. This work confirms the possibility of
      using molecularly imprinted polymers as ionophores for organic ion recognition in
      potentiometric transduction.

PMID- 20688508
TI  - Biocompatible molecularly imprinted polymers for the voltage regulated uptake and
      release of L-glutamate in neutral pH solutions.
AB  - A biocompatible device for the voltage dependent uptake and release of the neural
      transmitter L-glutamate in neutral pH solutions is demonstrated. The device
      consists of a gold electrode coated with molecularly imprinted, overoxidised
      polypyrrole (oPPy). It is shown here that oPPy can behave as an anion exchanger
      in neutral pH. The voltage dependent uptake and release of glutamate from the
      oPPy as well as the enantioselectivity of the polymer layer for L-glutamate over
      D-glutamate are investigated in neutral pH solutions using electrochemical quartz
      crystal microbalance techniques. The biocompatibility of the oPPy layer is
      demonstrated using retinae from young rats. The retinae were isolated and the
      dissociated cells were kept in culture for up to 1-week. The cells were exposed
      to the oPPy layers for 3 days, and there is no significant difference in the
      survival rate between the cells cultured on the oPPy layers and the control
      samples. Additionally the cell-polymer interface from cells grown directly on the
      oPPy layers is investigated using electron microscopy.

PMID- 20688509
TI  - Ultrasensitive immunosensor for the detection of cancer biomarker based on
      graphene sheet.
AB  - An ultrasensitive electrochemical immunosensor based on graphene sheet (GS) has
      been developed. GS was used to immobilize mediator thionine (TH), horseradish
      peroxidase (HRP) and secondary anti-prostate-specific antigen (PSA) antibody
      (Ab2) and the resulting nanostructure (GS-TH-HRP-Ab2) was used as the label for
      the immunosensor. With primary anti-PSA antibody (Ab1) also immobilized onto the
      GS, the immunosensor displayed a wide range of linear response (0.002-10 ng/mL),
      low detection limit (1 pg/mL), good reproducibility, selectivity and stability.
      The good performance of the immunosensor is attributed to the graphene sheet's
      high surface-to-volume ratio which allows the immobilization of a high-level of
      Ab1, Ab2, TH and HRP and its good electrical conductivity which can improve the
      electron transfer among TH, HRP, H2O2 and electrode. The immunosensor was used to
      detect the PSA contents in serum samples from patients and satisfactory test
      results were obtained in comparison with the ELISA test results. Thus, graphene
      based labels may provide many potential applications for the detection of
      different cancer biomarkers.

PMID- 20688510
TI  - Molecularly imprinted polymers for corticosteroids: analysis of binding
      selectivity.
AB  - In this work we prepared a library of cortisol-imprinted polymers via a
      sequential approach by combining 10 different functional monomers, 7 cross
      linkers and 5 porogen solvents. The best combinations of functional monomers,
      cross-linkers and porogen solvents in terms of cortisol binding were used to
      prepare three imprinted polymers--polyacrylamide-co-ethylene dimethacrylate
      (porogen: chloroform), poly-4-vinylpyridine-co-ethylene dimethacrylate (porogen:
      chloroform) and polyacrylamide-co-ethylene dimethacrylate (porogen: acetonitrile)
      -whose selectivity towards 10 synthetic corticosteroids and 4 natural steroidal
      hormones was tested. The experimental results obtained show how different
      combinations of functional monomers, cross-linkers and porogen solvents produce
      cortisol-imprinted polymers with very different selectivity patterns, and that a
      careful optimization of the pre-polymerization mixtures makes it possible to
      increase the number of target steroids recognized by the resulting imprinted
      polymer. Moreover, through the use of a Free-Wilson analysis of the binding
      selectivity, it has been possible to obtain insights on the steroidal structural
      motifs able to increase or decrease the molecular recognition of corticosteroids
      by the imprinted polymers.

PMID- 20688511
TI  - Virus hybrids as nanomaterials for biotechnology.
AB  - The current review describes advances in the field of bionanotechnology in which
      viruses are used to fabricate nanomaterials. Viruses are introduced as protein
      cages, scaffolds, and templates for the production of biohybrid nanostructured
      materials where organic and inorganic molecules are incorporated in a precise and
      a controlled fashion. Genetic engineering enables the insertion or replacement of
      selected amino acids on virus capsids for uses from bioconjugation to crystal
      growth. The variety of nanomaterials generated in rod-like and spherical viruses
      is highlighted for tobacco mosaic virus (TMV), M13 bacteriophage, cowpea
      chlorotic mottle virus (CCMV), and cowpea mosaic virus (CPMV). Functional
      biohybrid nanomaterials find applications in biosensing, memory devices,
      nanocircuits, light-harvesting systems, and nanobatteries.

PMID- 20688512
TI  - Performance of a sulfidogenic bioreactor and bacterial community shifts under
      different alkalinity levels.
AB  - The performance of a sulfidogenic bioreactor and the response of bacterial
      populations to influent alkalinity changes were investigated. The bioreactor
      reached 40% of sulfate removal efficiency (SRE) with 0 mg l(-1) of alkalinity,
      and single-stranded conformation polymorphism profiles showed that some members
      of Bacteroides, Dysgonomonas, Sporobacter, Quinella, and Citrobacter became
      dominant populations. 16S rRNA gene library analysis indicated that the
      Actinobacteria group increased from 0% in seed to 23% in sludge. An increase in
      alkalinity to 1300 mg l(-1) led to a rapid increase of SRE to 65% and changes in
      the bacterial community. Sequences representing Dysgonomonas, Raoultella,
      Kluyvera, and Phascolarctobacterium were now found. When alkalinity was deceased
      to 0 mg l(-1), SRE dropped and the bands representing Raoultella, Kluyvera, and
      Phascolarctobacterium disappeared, while bands representing Clostridium appeared.
      A second cycle of low/high alkalinity did not result in obvious changes to the
      bacterial community. These results indicate that the sulfidogenic bioreactor
      favored higher influent alkalinity and that the different functional microbial
      populations responded well to the alkalinity changes.

PMID- 20688513
TI  - Innovative biorefinery concept for sugar-based ethanol industries: production of
      protein-rich fungal biomass on vinasse as an aquaculture feed ingredient.
AB  - This study examined the potential of producing a protein-rich fungus, Rhizopus
      microsporus (var. oligosporus), as an aquaculture feed ingredient on vinasse
      generated during sugar-based ethanol fermentation. Optimization studies showed
      prolific fungal growth at pH 5.0 and 30 degrees C on vinasse with nutrient
      (nitrogen and phosphorus) supplementation. The molasses-vinasse resulted in the
      highest specific fungal biomass yield of 0.21 (g biomass increase/(g initial
      biomassxg soluble chemical oxygen demand (SCOD) removed)). Organic and inorganic
      matters were significantly reduced, e.g., 42.02% SCOD and 24.41% total dissolved
      solids. Thus, the treated effluent could be recycled as process water or used for
      land applications. The fungal biomass was found to have 45.55% crude protein with
      significantly high amino acids, arginine and threonine. The integration of
      innovative fungal technology with sugar-based ethanol production could provide an
      opportunity for producing food-grade fungal protein for animal feed application
      with simultaneous water reclamation.

PMID- 20688514
TI  - The acid tolerant L-arabinose isomerase from the food grade Lactobacillus sakei
      23K is an attractive D-tagatose producer.
AB  - The araA gene encoding an L-arabinose isomerase (L-AI) from the psychrotrophic
      and food grade Lactobacillus sakei 23K was cloned, sequenced and over-expressed
      in Escherichia coli. The recombinant enzyme has an apparent molecular weight of
      nearly 220 kDa, suggesting it is a tetramer of four 54 kDa monomers. The enzyme
      is distinguishable from previously reported L-AIs by its high activity and
      stability at temperatures from 4 to 40 degrees C, and pH from 3 to 8, and by its
      low metal requirement of only 0.8 mM Mn(2+) and 0.8 mM Mg(2+) for its maximal
      activity and thermostability. Enzyme kinetic studies showed that this enzyme
      displays a high catalytic efficiency allowing D-galactose bioconversion rates of
      20% and 36% at 10 and 45 degrees C, respectively, which are useful for commercial
      production of D-tagatose.

PMID- 20688515
TI  - Cathodes as electron donors for microbial metabolism: which extracellular
      electron transfer mechanisms are involved?
AB  - This review illuminates extracellular electron transfer mechanisms that may be
      involved in microbial bioelectrochemical systems with biocathodes. Microbially
      catalyzed cathodes are evolving for new bioprocessing applications for
      waste(water) treatment, carbon dioxide fixation, chemical product formation, or
      bioremediation. Extracellular electron transfer processes in biological anodes,
      were the electrode serves as electron acceptor, have been widely studied.
      However, for biological cathodes the question remains: what are the biochemical
      mechanisms for the extracellular electron transfer from a cathode (electron
      donor) to a microorganism? This question was approached by not only analysing the
      literature on biocathodes, but also by investigating known extracellular
      microbial oxidation reactions in environmental processes. Here, it is predicted
      that in direct electron transfer reactions, c-type cytochromes often together
      with hydrogenases play a critical role and that, in mediated electron transfer
      reactions, natural redox mediators, such as PQQ, will be involved in the
      bioelectrochemical reaction. These mechanisms are very similar to processes at
      the bioanode, but the components operate at different redox potentials. The
      biocatalyzed cathode reactions, thereby, are not necessarily energy conserving
      for the microorganism.

PMID- 20688516
TI  - Synthesis of new oxathiazinane dioxides and their in vitro cancer cell growth
      inhibitory activity.
AB  - New oxathiazinane dioxides have been derived from D- and L-serine and tested for
      their in vitro cell growth inhibitory activity toward SKBR3 breast cancer cells.
      (5R)-5-(4-(4'-Bromomethyl)phenyl)benzyloxymethyl-[1,3,4]-oxathiazinane-3,3
      dioxide showed a cytotoxicity of IC(50) approximately 10 microM.

PMID- 20688517
TI  - Crystal structure of the C183S/C217S mutant of human CA VII in complex with
      acetazolamide.
AB  - Human carbonic anhydrase VII (hCA VII) is a cytosolic member of the alpha-CA
      family. This enzyme is mainly localized in a number of brain tissues such as the
      cortex, hippocampus and thalamus and has been noted for its contribution in
      generating neuronal excitation and seizures. Recently, it has been also proposed
      that hCA VII may be involved in the control of neuropathic pain, thus its
      inhibition may offer a new approach in designing pain killers useful for
      combating neuropathic pain. We report here the X-ray crystallographic structure
      of a mutated form of human CA VII in complex with acetazolamide, a classical
      sulfonamide inhibitor. These crystallographic studies provide important
      implications for the rational drug design of selective CA inhibitors with
      clinical applications.

PMID- 20688518
TI  - S-benzylisothiourea derivatives as small-molecule inhibitors of indoleamine-2,3
      dioxygenase.
AB  - S-benzylisothiourea 3a was discovered by its ability to inhibit indoleamine-2,3
      dioxygenase (IDO) in our screening program. Subsequent optimization of the
      initial hit 3a lead to the identification of sub-muM inhibitors 3r and 10h, both
      of which suppressed kynurenine production in A431 cells. Synthesis and structure
      activity relationship of S-benzylisothiourea analogues as small-molecule
      inhibitors of IDO are described.

PMID- 20688519
TI  - Two distinct classes of novel pyrazolinecarboxamides as potent cannabinoid CB1
      receptor agonists.
AB  - The synthesis and SAR of 3-alkyl-4-aryl-4,5-dihydropyrazole-1-carboxamides 1-23
      and 1-alkyl-5-aryl-4,5-dihydropyrazole-3-carboxamides 24-27 as two novel
      cannabinoid CB(1) receptor agonist classes were described. The target compounds
      elicited high affinities to the CB(1) as well as the CB(2) receptor and were
      found to act as CB(1) receptor agonists. The key compound 19 elicited potent
      CB(1) agonistic and CB(2) inverse agonistic properties in vitro and showed in
      vivo activity in a rodent model for multiple sclerosis after oral administration.

PMID- 20688521
TI  - Evaluation of implant position and knee alignment after patient-specific
      unicompartmental knee arthroplasty.
AB  - Implant positioning and knee alignment are two primary goals of successful
      unicompartmental knee arthroplasty. This prospective study outlines the
      radiographic results following 32 patient-specific unicompartmental medial
      resurfacing knee arthroplasties. By means of standardized pre- and postoperative
      radiographs of the knee in strictly AP and lateral view, AP weight bearing long
      leg images as well as preoperative CT-based planning drawings an analysis of
      implant positioning and leg axis correction was performed.The mean preoperative
      coronal femoro-tibial angle was corrected from 7 degrees  to 1 degrees 
      (p<0.001). The preoperative medial proximal tibial angle of 87 degrees  was
      corrected to 89 degrees  (p<0.001). The preoperative tibial slope of 5 degrees 
      could be maintained. The extent of the dorsal femoral cut was equivalent to the
      desired value of 5mm given by the CT-based planning guide. The mean accuracy of
      the tibial component fit was 0mm in antero-posterior and +1mm in medio-lateral
      projection. Patient-specific fixed bearing unicompartmental knee arthroplasty can
      restore leg axis reliably, obtain a medial proximal tibial angle of 90 degrees ,
      avoid an implant mal-positioning and ensure maximal tibial coverage.

PMID- 20688522
TI  - Synthesis and biological evaluation of vitamin K derivatives as angiogenesis
      inhibitor.
AB  - Ten vitamin K(3) derivatives were synthesized and screened for anti-angiogenic
      activity. Results indicated that amine derivatives (1a-d) exerted a stronger
      inhibition effect on angiogenesis compared to alkyl derivatives (2a-d). In
      addition to being the most potent inhibitor, 1b also suppressed human umbilical
      vein endothelial cell tube formation and proliferation. These results suggest
      that vitamin K(3) amine derivatives with shorter alkyl chains, such as 1b, could
      be useful for developing anti-angiogenic agents.

PMID- 20688520
TI  - BST-2/tetherin: a new component of the innate immune response to enveloped
      viruses.
AB  - The interferon-inducible, transmembrane protein BST-2 (CD317, tetherin) directly
      holds fully formed enveloped virus particles to the cells that produce them,
      inhibiting their spread. BST-2 inhibits members of the retrovirus, filovirus,
      arenavirus and herpesvirus families. These viruses encode a variety of proteins
      to degrade BST-2 and/or direct it away from its site of action at the cell
      surface. Viral antagonism has subjected BST-2 to positive selection, leading to
      species-specific differences that presented a barrier to the transmission of
      simian immunodeficiency viruses (SIVs) to humans. This barrier was crossed by HIV
      1 when its Vpu protein acquired activity as a BST-2 antagonist. Here, we review
      this new host-pathogen relationship and discuss its impact on the evolution of
      primate lentiviruses and the origins of the HIV pandemic.

PMID- 20688523
TI  - N(G)-Acyl-argininamides as NPY Y(1) receptor antagonists: Influence of
      structurally diverse acyl substituents on stability and affinity.
AB  - N(G)-Acylated argininamides, covering a broad range of lipophilicity (calculated
      logD values: -1.8-12.5), were synthesized and investigated for NPY Y(1) receptor
      (Y(1)R) antagonism, Y(1)R affinity and stability in buffer (N(G)-deacylation,
      yielding BIBP 3226). Broad structural variation of substituents was tolerated.
      The K(i) (binding) and K(b) values (Y(1)R antagonism) varied from low nM to one
      digit muM. Most of the compounds proved to be sufficiently stable at pH 7.4 over
      90min to determine reliable pharmacological data in vitro. Exceptionally high
      instability was detected when a succinyl moiety was attached to the guanidine,
      probably, due to an intramolecular cleavage mechanism.

PMID- 20688524
TI  - Synthesis and properties of macrolones characterized by two ether bonds in the
      linker.
AB  - In this paper synthesis of macrolones 1-18 starting from azithromycin is
      reported. Two key steps in the construction of the linker between macrolide and
      quinolone moiety, are formation of central ether bond by alkylation of
      unactivated OH group, and formation of terminal C-C bond at 6-position of the
      quinolone unit. Due to the difficulty in formation of these two bonds the study
      of alternative synthetic methodologies and optimization of the conditions for the
      selected routes was required. Formation of C-4''-O-ether bond was completed by
      modified Michael addition, whereas O-alkylation via diazonium cation proved to be
      the most effective in formation of the central allylic or propargylic ether bond.
      Comparison of Heck and Sonogashira reaction revealed the former as preferred
      route to the C-C bond formation at C(6) position of the quinolone unit. Most of
      the target compounds exhibited highly favorable antibacterial activity against
      common respiratory pathogens, without significant cytotoxicity profile when
      tested in vitro on eukaryotic cell lines.

PMID- 20688525
TI  - Ultrastructure of the compound eyes in the hangingfly Bittacus planus Cheng
      (Mecoptera: Bittacidae).
AB  - The ultrastructure of the apposition eyes in the hangingfly Bittacus planus Cheng
      was investigated using transmission electron microscopy. The compound eyes are
      composed of approximately 1000 contiguous ommatidia, each of which consists of a
      biconvex cornea, a crystalline cone, eight retinula cells, two primary pigment
      cells, and 12 secondary pigment cells. The rhabdom is of fused-type and formed by
      the rhabdomeres from eight retinula cells that run from the cone to the basal
      lamina, although the rhabdomere from the basal retinula cell (R8) only
      contributed to the lowest part of the rhabdom. The pigment granules are spread
      evenly in the primary pigment cells but are concentrated at the proximal and
      distal ends in the secondary pigment cells, and close to the rhabdom in retinula
      cells. The rhabdom is peculiar for the presence of gaps at the outer corner of
      each two adjoining rhabdomeres in different levels of retinula cell except for
      the proximal zone.

PMID- 20688526
TI  - Structural and mechanistic Information on c(1) ion formation in collision-induced
      fragmentation of peptides.
AB  - The formation of c(1) ions during collision-induced fragmentation of peptides
      with asparagine, ornithine, or glutamine at the N-terminal position 2 has been
      studied. For this purpose, the corresponding fragment ion spectra of a large set
      of synthetic peptides were investigated. It is demonstrated that the c(1) ion
      intensity depends on the nature of the second residue in the N-terminal dipeptide
      motif as well as on the peptide length. It is shown that the formation of c(1)
      ions proceeds by two competing mechanisms. One mechanism is the secondary
      fragmentation of the b(2) ion, the efficiency of which shows only a minor
      dependency on the complete peptide sequence. The other mechanism is the direct
      formation from the molecular ion, which is identified to be connected with
      sequence-specific c(1) ion intensities. A model for this latter mechanism is
      proposed based on the analysis of the formation and secondary fragmentation of
      the z(max-1) ion, which is the complementary ion to the c(1) ion. Additional
      evidence is obtained by investigation of peptides with ornithine in N-terminal
      position 2, which in general exhibit c(1) ion intensities intermediate between
      the asparagine- and glutamine-containing species. The data presented support the
      reliable assignment of N-terminal dipeptide motifs using collision-induced
      dissociation.

PMID- 20688527
TI  - The relative charge ratio between C and N atoms in amide bond acts as a key
      factor to determine peptide fragment efficiency in different charge states.
AB  - The influence of charge state on the peptide dissociation behavior in tandem mass
      spectrometry (MS/MS) is worthy of discussion. Comparative studies of singly- and
      doubly-protonated peptide molecules are performed to explore the effect and
      mechanism of charge state on peptide fragmentation. In view of the charge
      directed cleavage of protonated peptides described in the mobile proton model,
      radiolytic oxidation was applied to change the charge distribution of peptides
      but retain the sequence. Experimental studies of collision energy-dependent
      fragmentation efficiencies coupled with quantum chemical calculations indicated
      that the cleavage of ARRA and its side-chain oxidation products with oxygen atoms
      added followed a trend that doubly-protonated peptides fragment more easily than
      singly-protonated forms, while the oxidation product with the guanidine group
      deleted showed the opposite trend. By analyzing the charge distribution around
      the amide bonds, we found that the relative charge ratios between C and N atoms
      (Q(C)/Q(N)) in the amide bonds provided a reasonable explanation for peptide
      fragmentation efficiencies. An increase of the Q(C)/Q(N) value of the amide bond
      means that a peptide fragments more easily, and vice versa. The results described
      in this paper provide an experimental and calculation strategy for predicting
      peptide fragmentation efficiency.

PMID- 20688529
TI  - Test-retest reliability of quadriceps muscle function outcomes in patients with
      knee osteoarthritis.
AB  - Quadriceps muscle weakness and the underlying neuromuscular deficits have been
      increasingly studied over the last few years in patients with knee
      osteoarthritis, but the applied methodologies have never been validated for this
      specific population. The aim of this study was to investigate test-retest
      reliability of several quadriceps muscle function outcomes in patients with knee
      osteoarthritis both before and after knee arthroplasty surgery. Ten preoperative
      and 20 postoperative patients participated in two identical testing sessions. A
      series of voluntary and/or electrically stimulated contractions of the involved
      quadriceps with concomitant torque and electromyographic recordings were used to
      characterize muscle strength, muscle activation and muscle contraction
      properties. Vastus lateralis morphology (thickness and fascicle pennation angle)
      was also assessed using ultrasonography. Overall, good reliability scores were
      observed for the majority of the 13 assessed variables (nine variables with
      intraclass correlation coefficients >0.75, 12 variables with coefficients of
      variation <15%). The most reliable testing protocol for patients with knee
      osteoarthritis would entail the assessment of (1) isometric maximal voluntary
      torque for evaluating muscle strength, with (2) simultaneous vastus lateralis
      electromyographic activity for evaluating muscle activation, (3) potentiated
      (resting) doublet peak torque for evaluating muscle contractility, and (4) vastus
      lateralis thickness for evaluating muscle size.

PMID- 20688528
TI  - Living in the context of poverty and trajectories of breast cancer worry,
      knowledge, and perceived risk after a breast cancer risk education session.
AB  - OBJECTIVES: The purpose of this paper was to demonstrate how living in
      neighborhoods with high levels of poverty (while controlling for personal income)
      impacts personal characteristics, which in turn impacts retention of breast
      cancer risk knowledge and changes in worry and perceived risk. METHODS: The data
      from this project come from a larger, National Cancer Institute-funded study that
      included a pretest, a breast cancer risk education session, a posttest, the
      option of an individualized risk assessment via the Gail Model and three follow
      up phone calls over the next 9 months. RESULTS: The percent of individuals living
      below poverty in the community in which the participant resided was predictive of
      the personal characteristics assessed, and these characteristics were predictive
      of changes in breast cancer worry and knowledge across time. CONCLUSION:
      Differentiation of self and monitoring, two of the individual characteristics
      that seem to allow people to process and use information to make "rational"
      decisions about health care, seem to be impacted by the necessity for adaptation
      to a culture of poverty. Thus, as a health care community, we need to tailor our
      messages and our recommendations with an understanding of the complex
      intersection of poverty and health care decision making.

PMID- 20688530
TI  - Activation level of extensor carpi ulnaris affects wrist and elbow acceleration
      responses following simulated forward falls.
AB  - The main objective of this study was to measure the acceleration response at the
      wrist and elbow as a function of different levels of isometric forearm muscle
      activation during the impact phase of a simulated forward fall. A seated human
      pendulum was designed to impact the hands of 28 participants while maintaining
      one of four levels of isometric muscle activation (12%, 24%, 36% and 48% maximal
      voluntary exertion (MVE)) in the extensor carpi ulnaris muscles. The acceleration
      responses including peak acceleration (PA), acceleration slope (AS) and time to
      peak acceleration (TPA) were measured at the wrist and elbow along two axes
      (axial and off-axis) with two low mass surface mounted accelerometers. At the
      wrist, significant muscle activation effects were found for PA(off), AS(axial),
      AS(off), such that they increased as muscle activation increased from baseline to
      48% MVE. At the elbow, a similar response was noted, with the acceleration
      variables increasing as muscle activation level increased, except for AS(off).
      The results suggest that increases in muscle activation from 12% to 48% MVE
      stiffen the forearm complex and increase the transmissibility of the impact
      reaction force shock waves through the forearm.

PMID- 20688531
TI  - Development of new hepaticoenteric collateral pathways after hepatic arterial
      skeletonization in preparation for yttrium-90 radioembolization.
AB  - PURPOSE: Development of new hepaticoenteric anastomotic vessels may occur after
      endovascular skeletonization of the hepatic artery. Left untreated, they can
      serve as pathways for nontarget radioembolization. The authors reviewed the
      incidence, anatomy, management, and significance of collateral vessel formation
      in patients undergoing radioembolization. MATERIALS AND METHODS: One hundred
      thirty-eight treatments performed on 122 patients were reviewed. Each patient
      underwent a preparatory digital subtraction angiogram (DSA) and embolization of
      all hepaticoenteric vessels in preparation for yttrium-90 ((90)Y) administration.
      Successful skeletonization was verified by C-arm computed tomography (CACT) and
      technetium-99m macroaggregated albumin ((99m)TcMAA) scintigraphy. During the
      subsequent treatment session, DSA and CACT were repeated before administration of
      (90)Y, and the detection of extrahepatic perfusion prompted additional
      embolization. RESULTS: Forty-two patients (34.4%) undergoing 43 treatments
      (31.2%) required adjunctive embolization of hepaticoenteric vessels immediately
      before (90)Y administration. Previous scintigraphy findings showed extrahepatic
      perfusion in only three cases (7.1%). Vessels were identified by DSA in 54.1%, by
      CACT in 4.9%, or required both in 41.0%. The time interval between angiograms did
      not correlate with risk of requiring reembolization (P = .297). A total of 19.7%
      of vessels were new collateral vessels not visible during the initial
      angiography. Despite reembolization, three patients (7.1%) had gastric or
      duodenal ulceration, compared with 1.3% who never had visible collateral vessels,
      all of whom underwent whole-liver treatment with resin microspheres (P = .038).
      CONCLUSIONS: Development of collateral hepaticoenteric anastomoses occurs after
      endovascular skeletonization of the hepatic artery. Identified vessels may be
      managed by adjunctive embolization, but patients appear to remain at increased
      risk for gastrointestinal complications.

PMID- 20688532
TI  - Temperature isotherms during pulmonary cryoablation and their correlation with
      the zone of ablation.
AB  - PURPOSE: To determine the expected ablation zone size and associated isotherms
      when using clinically available percutaneous cryoprobes for pulmonary
      cryoablation in a porcine lung model. MATERIALS AND METHODS: Seven ablations were
      performed in the lungs of three adult pigs using clinically available 2.4-mm
      cryoprobes (Endocare, Inc, Irvine, California) and a 10-minute double-freeze
      protocol. Five 18-gauge thermocouples were positioned at 5-mm increments (ie, 5,
      10, 15, 20, and 25 mm) from the cryoprobe. Real-time tissue temperatures were
      recorded during the cryoablation. The isotherms obtained during the ablation and
      the pathological ablation zones were measured. RESULTS: The pathologic zone of
      complete necrosis had a mean diameter of 2.4 + or - 0.2 cm, with a mean area of
      4.6 + or - 0.6 cm(2) and a circularity of 0.95 + or - 0.04. In comparison, the
      mean diameter (+ or - standard deviation) of the 0 degrees C, -20 degrees C, and 
      40 degrees C isotherms were 3.1 + or - 0.2 cm, 2.3 + or - 0.3 cm, and 1.8 + or -
      0.4 cm, respectively. The -20 degrees C isotherm was most closely related to the
      pathologic zone of ablation. CONCLUSIONS: This study establishes the temperature
      isotherms and associated ablation zone size that can be expected with modern
      percutaneous cryoprobes in an in vivo porcine lung model.

PMID- 20688533
TI  - Intraarterial thrombolysis and stent placement for acute basilar artery
      occlusion.
AB  - PURPOSE: To study retrospectively the prognostic factors for acute basilar artery
      occlusion treated with intraarterial thrombolysis and stent placement. MATERIALS
      AND METHODS: Within 3-48 hours of disease onset, 52 patients with basilar artery
      occlusion were treated with emergency intraarterial thrombolysis with recombinant
      tissue plasminogen activator (rtPA) or urokinase (UK) or intraarterial
      thrombolysis combined with stent placement. Sixteen patients simultaneously
      received stent placement for the partial recanalization of basilar artery
      occlusion after intraarterial thrombolysis. The National Institutes of Health
      Stroke Scale (NIHSS) scores and the modified Rankin Scale (mRS) scores of the
      patients were estimated. RESULTS: A favorable clinical outcome occurred in 22
      patients (42.3%), and 20 patients (38.5%) died. The survival rate was 61.5% (32
      patients). Successful recanalization of basilar artery occlusion was achieved in
      24 patients (46.2%), and partial recanalization was achieved in 16 patients
      (30.7%). The rate of recanalization was 76.9%. NIHSS scores less than 14,
      treatment time window less than 24 hours, and a good recanalization were markedly
      correlated with good clinical prognosis. NIHSS scores less than 14 and treatment
      time window less than 24 hours were significantly correlated with recanalization.
      NIHSS scores less than 14 and good recanalization could act as independent
      predictors for clinical prognosis. CONCLUSIONS: NIHSS scores less than 14 on
      admission and successful recanalization can predict favorable outcome for
      patients with basilar artery occlusion. This study shows that intraarterial
      thrombolysis and stent placement may be a useful treatment for acute basilar
      artery occlusion.

PMID- 20688534
TI  - Chemoembolization follow-up of hepatocellular carcinoma with MR imaging:
      usefulness of evaluating enhancement features on one-month posttherapy MR imaging
      for predicting residual disease.
AB  - PURPOSE: To determine the sensitivity, specificity, and accuracy of contrast
      enhanced magnetic resonance (MR) imaging performed 1 month after localized
      chemotherapy as a measure of tumor response, before detectable changes in size.
      MATERIALS AND METHODS: This trial was approved by the authors' institutional
      review board and was compliant with the Health Insurance Portability and
      Accountability Act (HIPAA). Inclusion criteria selected patients receiving
      chemoembolization for hepatocellular carcinoma (HCC) with MR imaging within 2
      months before treatment, in addition to MR imaging after treatment at 1 month and
      6 months. Pathology was used as a surrogate for 6-month follow-up if the patient
      underwent interval transplantation. The final population consisted of 23 tumors
      (occurring within 21 patients). MR imaging studies were evaluated separately by
      two radiologists. Tumors were scored as showing complete loss of enhancement or
      as showing some residual tissue enhancement. Changes in T1 and T2 signal and
      perilesional enhancement were tabulated and recorded. Lesion size was also
      measured on all MR imaging studies by using a one-dimensional measure of the
      longest dimension. Increase in tumor size from 1-6 months of 20% or greater was
      used as confirmation of residual disease. In 5 of 23 tumors, review of pathology
      served as the surrogate standard. Sensitivity, specificity and accuracy were
      computed for each rater. RESULTS: The sensitivity, specificity, and accuracy of 1
      month follow-up MR imaging were 71.4-85.7%, 100%, and 91.3-95.7%. There was a
      high degree of agreement between the two readers for both the 1-month (kappa =
      0.88) and 6-month (kappa = 1.0) MR imaging studies. CONCLUSIONS: This
      investigation shows high accuracy for using tumor enhancement features on 1-month
      posttherapy MR imaging to predict residual disease after chemoembolization of
      HCC.

PMID- 20688535
TI  - Temporary placement of a covered, retrievable, barbed stent for the treatment of
      hormone-induced benign prostatic hyperplasia: technical feasibility and
      histologic changes in canine prostates.
AB  - PURPOSE: To evaluate the technical feasibility of a covered, retrievable, barbed
      prostatic stent and to determine stent-induced histologic changes of the prostate
      in canine benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: BPH was
      induced in 8 male beagles by administration of dihydrotestosterone and beta
      estradiol. Under fluoroscopy guidance, covered, retrievable, barbed stents were
      placed in the prostatic urethras. Urethrograms were obtained every three to 4
      weeks until sacrifice. The stents were removed 8 weeks after placement. The dogs
      were sacrificed immediately (group A, n = 4) and 8 weeks after stent removal
      (group B, n = 4). Histologic changes of prostates were microscopically evaluated.
      RESULTS: Stent placement was technically successful in all dogs. The diameters of
      the prostatic urethra were 14.1 mm + or - 0.5 and 13.7 mm + or - 0.5 on
      urethrograms obtained immediately after and 8 weeks after stent removal (P =
      .268). Stent removal was successful in all dogs except one, in which the stent
      was obstructed by stone formation. Small sandy stones were identified attached to
      the removed stents of two dogs. Histologic examination revealed extensive
      prostatic glandular atrophy involving 95.1% + or - 2.2 (group A) and 94.5% + or -
      2.4 (group B) of entire prostate (P = .773). CONCLUSIONS: A covered, retrievable,
      barbed prostatic stent seems to be feasible for use in hormone-induced canine
      BPH. The stent induced prostatic urethral dilatation, and extensive prostatic
      glandular atrophy persisted up to 8 weeks after stent removal.

PMID- 20688536
TI  - Spinal cord protection with a cerebrospinal fluid drain in a patient undergoing
      thoracic endovascular aortic repair.
AB  - Paralysis and paraparesis are dreaded complications of thoracic endovascular
      aortic repair (TEVAR) that occur with an incidence of 2%-6%. Risks factors
      include the type of thoracic aortic pathology treated, coverage of the left
      subclavian artery origin without revascularization, concomitant infrarenal
      abdominal aortic aneurysm repair, extent of stent graft coverage of the thoracic
      aorta, and renal failure. Cerebral spinal fluid (CSF) drains have been advocated
      as one of several protective strategies to prevent spinal cord ischemia. This
      case discussion briefly addresses the evidence supporting the use of CSF drains
      in patients undergoing TEVAR and offers an algorithm for managing CSF drains.

PMID- 20688537
TI  - Technetium-99m-methyl diphosphonate bone scintigraphy may be helpful in
      preoperative planning for vertebroplasty in multiple myeloma: two cases.
AB  - Favorable vertebroplasty outcomes reflect accurate preoperative identification of
      vertebral fracture targets, operator proficiency, and assiduous fracture
      aftercare. Conventional teaching is that nuclear bone scintigraphy is not helpful
      in the management of osteolytic myeloma bone disease. Nuclear bone scintigraphy
      in two patients with multiple myeloma and vertebral fracture pain convincingly
      identified the fracturing vertebral level and provided confidence that
      synchronous vertebral fractures were not missed, whereas neither had been
      appreciated by either radiography or magnetic resonance imaging.

PMID- 20688538
TI  - Interaction between spinal opioid and adenosine receptors in remote cardiac
      preconditioning: effect of intrathecal morphine.
AB  - OBJECTIVES: Intrathecal morphine is cardioprotective and also triggers spinal
      adenosine release. This study investigated the role of spinal and peripheral
      adenosine receptors in intrathecal morphine cardioprotection. DESIGN: A
      randomized, prospective study. SETTING: A university research laboratory.
      PARTICIPANTS: Seventy-two male Sprague-Dawley rats. INTERVENTIONS: Anesthetized,
      open-chest, male Sprague-Dawley rats were assigned to 1 of 10 treatment groups 3
      days after intrathecal catheter placement. Intrathecal morphine cardioprotection
      was induced with 3 MUg/kg of morphine. Intrathecal normal saline was used as the
      control. The adenosine-receptor antagonist 8-(p-sulfophenyl) theophylline (50
      MUg/kg or 7.5 mg/kg) was given via intrathecal or intravenous routes,
      respectively, either 10 minutes before or immediately after morphine or saline.
      Ischemia reperfusion injury then was induced by 30 minutes of left coronary
      artery occlusion followed by 120 minutes of reperfusion. MEASUREMENTS AND MAIN
      RESULTS: Infarct size, as a percentage of the area at risk, was determined by
      2,3,5-triphenyltetrazolium chloride staining. This was reduced significantly in
      the morphine group (25% +/- 5%) compared with the control (58% +/- 3%, p < 0.05).
      The addition of intravenous 8-SPT either before or after morphine significantly
      attenuated the cardioprotective effect. In comparison, intrathecal administration
      of 8-(p-sulfophenyl) theophylline before but not after morphine attenuated the
      cardioprotective effects of intrathecal morphine. CONCLUSIONS: Both central and
      peripheral adenosine receptors are involved in the signaling of intrathecal
      morphine preconditioning. Central receptors are important in the initiation of
      the process, whereas peripheral receptors have a role in ongoing mediation of the
      protective effect.

PMID- 20688539
TI  - Dose-dependent systolic contribution of differentiated stem cells in post-infarct
      ventricular function.
AB  - BACKGROUND: Differentiation of bone marrow stem cells toward cardiomyocytes has
      been widely reported in vitro. However, optimum cell types and mechanisms leading
      to functional improvement in cardiac cell therapy remain unresolved. There is
      limited evidence showing a dose-dependent effect of transplanted cells in
      contributing to functional recovery. This study showed that cell transplantation
      of differentiated cardiomyocyte-like cells (CLCs) and undifferentiated
      mesenchymal stem cells (MSCs) dose-dependently improved left ventricular function
      in a rat myocardial infarction model. METHODS: At 1 week after infarction in
      Wistar rats, 1 * 10(6) MSCs (n = 9) or CLCs (n = 9) and 5 * 10(6) MSCs (n = 18)
      or CLCs (n = 15) were injected into peri-infarcted myocardium to study their
      effect after 6 weeks. RESULTS: High-dose CLCs exhibited a dose-response that was
      significantly more effective than MSCs in recovering cardiac contractility.
      Superiority of CLCs over MSCs was demonstrated in load-independent measurement of
      the end-systolic pressure-volume relationship and pre-load recruitable stroke
      work, but not in the end-diastolic pressure-volume relationship. These findings
      showed a unique systolic role of CLCs in contractility recovery. Functional
      improvement mediated by MSCs was mainly derived from preservation of endogenous
      myocyte function and restriction of chamber dilatation by enhancing
      intramyocardial angiogenesis during post-infarct ventricular remodeling.
      Engrafted CLCs showed better survival, were strategically integrated into
      myofiber-associated collagen V matrix, and exhibited mature sarcomeric cross
      striations. Vascular differentiation, but not cardiac, was observed with MSCs.
      CONCLUSION: These cell type-specific effects suggest that committing stem cells
      to a cardiac phenotype ex vivo promoted mechanical and functional integration of
      CLCs into the myofibrillar syncytium of infarcted myocardium.

PMID- 20688540
TI  - Echocardiographic assessment of flow across continuous-flow ventricular assist
      devices at low speeds.
AB  - BACKGROUND: Testing of native myocardial function in patients with continuous
      flow pumps is challenging as reduction/cessation of the pump could result in
      regurgitation, although the amount and significance of this regurgitation remains
      unknown. The aim of this study was to determine the optimal speed at which to
      assess the native left ventricular (LV) function and the physiologic response to
      speed reduction. METHODS: Fifteen male patients with a HeartMate II (HMII) device
      were studied prospectively on 46 occasions. Measurements were performed serially
      at three device speed settings: baseline speed; 6,000 rpm; and either 5,000 rpm
      (Group A) or 4,000 rpm (Group B). The device's forward and reverse velocity
      (Vmax(f), Vmax(r)), forward and reverse velocity time integral (VTI(f), VTI(r))
      and blood volume (BV) were also measured using Doppler with LV echocardiographic
      parameters and peripheral hemodynamics. RESULTS: No adverse incidents were
      reported. Speed reduction to 6,000 rpm resulted in a significant decrease in
      Vmax(f), VTI(f) and BV. There was no significant difference in either forward or
      reverse flow with further speed reduction in either group. Speed reduction to
      <6,000 rpm did not have a significant effect on LV loading. CONCLUSIONS: Speed
      reduction in patients with the HMII device is safe. There was no difference
      between 6,000 rpm and lower speeds, suggesting that 6,000 rpm is sufficient to
      assess native myocardial function. The absence of significant retrograde filling
      suggests that LV loading is a physiologic response to speed reduction at 6,000
      rpm.

PMID- 20688541
TI  - Barriers and facilitators to engagement in HIV clinical care in the Deep South:
      results from semi-structured patient interviews.
AB  - Delayed entry into HIV clinical care and poor retention during care has been
      associated with increased morbidity and mortality. To characterize the reasons
      for patients who eventually did enter HIV care after a delay and/or returned to
      care after a gap of 6 months or more, 130 semi-structured interviews about
      barriers to and facilitators for prompt entry into and sustained HIV clinical
      care were conducted in a clinic setting in the Deep South; responses were coded
      and analyzed quantitatively. Barriers or facilitators were positioned within
      superordinate categories of personal and structural barriers or facilitators and
      denial. Personal barriers for entry into care outweighed structural barriers,
      with denial being reported by 74% of the sample. Barriers to retention in care
      were more evenly distributed between personal and structural barriers, with
      denial being a barrier for 24%. Because of the high incidence of denial-based
      barriers, the role of this barrier and its resolution should be explored further.

PMID- 20688542
TI  - Acute, avulsion fractures of the medial epicondyle while throwing in youth
      baseball players: a variant of Little League elbow.
AB  - HYPOTHESIS: The young throwing athlete is susceptible to medial elbow injury due
      to valgus overload. We hypothesized that this injury can occur during the
      throwing motion with an acute episode of medial elbow pain resulting in an
      inability to effectively participate in throwing activities. In addition,
      appropriate treatment of acute, medial epicondyle avulsion fractures in baseball
      players can result in an asymptomatic elbow with subsequent return to play within
      a year of injury. MATERIALS AND METHODS: A case series of all youth baseball
      players with medial epicondyle avulsion fractures that occurred while throwing
      were identified. We studied several variables, including demographics, adherence
      to USA Baseball youth pitching recommendations, clinical history, radiographic
      findings, treatment, and outcome. RESULTS: Eight skeletally immature baseball
      players, who were a mean age of 13 years (range, 11-15 years), presented with
      medial epicondyle fractures that occurred while throwing. All 8 players
      experienced sudden pain during throwing, and all 5 players with appropriate age
      and position qualifications did not conform to the USA Baseball youth pitching
      recommendations. Anteroposterior radiographs documented average fracture
      displacement of 5.1 mm (range, 2.5-10 mm). Five of 8 players had 5 mm or less of
      displacement and were selected for nonoperative treatment. Three of 8 players had
      more than 5 mm of displacement and underwent open reduction and internal
      fixation. All players were able to return to play at an average of 7.6 months
      (range, 4-10 months). DISCUSSION: Medial epicondyle avulsion fractures can occur
      with a characteristic acute presentation while throwing in youth baseball
      players. Prevention may be possible when conforming to established USA Baseball
      youth pitching recommendations. Once an acute medial epicondyle avulsion fracture
      occurs, these injuries may be managed using published treatment algorithms, with
      successful return to play in less than 1 year.

PMID- 20688543
TI  - Cardiac changes in epilepsy.
AB  - Epilepsy and seizures can have a dramatic effect on the autonomic nervous system
      by involvement of the central autonomic control centers. The peri-ictal changes
      can lead to short-term alteration of cardiac functions in patients with seizures,
      and are partially hemispheric specific. Changes in heart rhythm, conduction and
      even subtle signs of ischemia have been reported. Ictal asystole and the lock
      step phenomenon during seizures play an important role in the pathophysiology of
      SUDEP. In patients with longlasting epilepsy and multiple seizures, there are now
      convincing arguments for a chronic dysfunction of the autonomic nervous system.
      In this sense, heart rate variability can be considered as a biomarker of
      autonomic dysfunction in epilepsy. Early recognition of these short- and long
      term cardiac effects will become useful in predicting seizures and in guiding
      more individualized treatment in the near future.

PMID- 20688544
TI  - Long term outcome of benign childhood epilepsy with centrotemporal spikes: Dutch
      Study of Epilepsy in Childhood.
AB  - PURPOSE: To determine long-term outcome in a cohort of children with newly
      diagnosed benign childhood epilepsy with centrotemporal spikes (BECTS). METHODS:
      29 children with BECTS were included in the Dutch Study of Epilepsy in Childhood.
      Each child was followed for 5 years, and subsequently contacted 12-17 years after
      enrolment to complete a structured questionnaire. Twenty children had typical
      BECTS, nine had atypical BECTS (age at onset <4 years, developmental delay or
      learning difficulties at inclusion, other seizure types, atypical EEG
      abnormalities). RESULTS: Mean age at onset of epilepsy was 8.0 years with slight
      male preponderance. Most common seizure-types before enrolment were generalized
      tonic-clonic seizures (GTCS) and simple partial seizures; in 86% of the children
      seizures occurred during sleep. After 12-17 years, 96% had a terminal remission
      (TR(F)) of more than 5 years and 89% of more than 10 years. Mean duration of
      epilepsy was 2.7 years; mean age at reaching TR(F) was 10.6 years. Many children
      (63%) had experienced one or more (secondary) GTCS. Antiepileptic drugs were used
      by 79% of the children with a mean duration of 3.0 years. None of the children
      seemed to have developed learning problems or an arrest of cognitive development
      during follow-up. No significant differences were observed in patient
      characteristics or outcome between children with typical BECTS and children with
      atypical BECTS. CONCLUSIONS: All children in our cohort, both those with typical
      and atypical BECTS, had a very good prognosis with high remission rates after 12
      17 years. None of the predictive factors for disease course and outcome observed
      in earlier studies (other seizure types, age at onset, multiple seizures at
      onset) were prognostic in our cohort.

PMID- 20688545
TI  - Multi-voxel magnetic resonance spectroscopy at 3 T in patients with idiopathic
      generalised epilepsy.
AB  - PURPOSE: The objective of our study was to gain further insight into the extent
      of local metabolic alterations in patients with idiopathic generalised epilepsy
      (IGE), respectively, the subgroup with generalised tonic-clonic seizures (GTCS).
      The extent of regional metabolic involvement perhaps indicates the key structures
      in generation of seizures and involvement of specific network of dysfunction.
      METHODS: Using the multi-voxel technique at a 3 T MRI Scanner metabolite levels
      of 25 age-matched healthy controls and 18 patients with GTCS were obtained from
      the basal ganglia, insular cortex, cingulum, hippocampus and along both
      hemispheres in the fronto-parietal white and grey matter. RESULTS: Group analysis
      of GTCS patients versus healthy controls revealed significant (p < 0.05) decrease
      of tNAA in the cortex of the central region and cingulum, but also in the
      thalami. Glx was elevated broadly in both hemispheres, in particular in central
      region, cingulum, insular cortex and left putamen, yet also in the right
      thalamus. Cho and mI demonstrated a significant coincidental decrease pronounced
      in the grey and white matter of the central region. Significant metabolic
      correlation (p <= 0.05) based on tNAA, respectively, Glx occurred between the
      thalamus and the central region, cingulum, putamen and medial frontal cortex. In
      patients with > 2 tonic-clonic seizures in the last 12 months a trend towards
      higher Glx and lower tNAA levels was observed. DISCUSSION: Our results
      demonstrate the altered metabolic interconnection of cerebral anatomic regions in
      patients with GTCS, in particular the major role of basal ganglia-central region
      relay in seizure generation.

PMID- 20688546
TI  - Use of noninvasive interactive neurostimulation to improve short-term recovery in
      patients with surgically repaired bimalleolar ankle fractures: a prospective,
      randomized clinical trial.
AB  - We undertook a trial with 60 patients who had undergone operative reduction and
      internal fixation of bimalleolar, AO type B2 ankle fractures with comminution.
      Patients were randomized into 2 groups, one of which received postoperative
      treatment using a noninvasive interactive neurostimulation device (InterX) and
      the other with a sham device. The trial was designed to test the hypothesis that
      incorporation of noninvasive interactive neurostimulation into the rehabilitation
      protocol would result in reduced pain, increased range of motion, reduced edema,
      and reduced consumption of pain medication, in comparison with the sham therapy
      group. Outcome measurements included the patient's subjective assessment of level
      of pain, range of motion, and the extent of edema in the involved ankle, and the
      use of ketorolac for postoperative control of pain. The results showed
      significantly better results in the patients receiving treatment with active
      neurostimulation (repeated measures analysis of variance, P < .001).

PMID- 20688547
TI  - Backtracking RAS mutations in high hyperdiploid childhood acute lymphoblastic
      leukemia.
AB  - High hyperdiploidy is the single largest subtype of childhood acute lymphoblastic
      leukemia (ALL) and is defined by the presence of 51-68 chromosomes in a
      karyotype. The 5 or more extra chromosomes characterizing this subtype are known
      to occur in a single mitotic event, prenatally. We screened for RAS mutations
      among 517 acute childhood leukemias (including 437 lymphocytic, of which 393 were
      B-cell subtypes) and found mutations in 30% of high hyperdiploids compared to
      only 10% of leukemias of other subtypes (P<0.0001). We assessed whether KRAS
      mutations occurred before birth using a PCR-restriction enzyme-mediated Taqman
      quantitative PCR reaction, and found no evidence for prenatal KRAS mutations in
      14 patients tested. While RAS mutations were previously associated with prior
      chemical exposures in childhood and adult leukemias, in this study RAS-mutated
      cases were not significantly associated with parental smoking when compared to
      study controls. IGH rearrangements were backtracked in three RAS-positive
      patients (which were negative for KRAS mutation at birth) and found to be evident
      before birth, confirming a prenatal origin for the leukemia clone. We posit a
      natural history for hyperdiploid leukemia in which prenatal mitotic catastrophe
      is followed by a postnatal RAS mutation to produce the leukemic cell phenotype.

PMID- 20688548
TI  - A new cryptic ins(11;1)(q23;q21q31) detected in a t(1;8;11)(q21;p21;q23) in a
      baby with acute myeloid leukemia FAB AML-M5.

PMID- 20688549
TI  - AnalyzeNNLS: magnetic resonance multiexponential decay image analysis.
AB  - Exponential decays are fundamental to magnetic resonance imaging, yet adequately
      sampling and analyzing multiexponential decays is rarely attempted. The advantage
      of multiexponential analysis is the quantification of sub-voxel structure caused
      by water compartmentalization, with application as a non-invasive imaging
      biomarker for myelin. We have developed AnalyzeNNLS, software designed
      specifically for multiexponential decay image analysis that has a user-friendly
      graphical user interface and can analyze data from many MR manufacturers.
      AnalyzeNNLS is a simple, platform independent analysis tool that was created
      using the extensive mathematical and visualization libraries in Matlab, and
      released as open source code allowing scientists to evaluate, scrutinize,
      improve, and expand.

PMID- 20688551
TI  - Vitamin D and diabetes: much ado about nothing?

PMID- 20688550
TI  - Evolution of the spectrin-based membrane skeleton.
AB  - A group of four proteins - spectrin, ankyrin, 4.1 and adducin - evolved with the
      metazoa. These membrane-cytoskeletal proteins cross-link actin on the cytoplasmic
      face of plasma membranes and link a variety of transmembrane proteins to the
      cytoskeleton. In this paper, the evolution of these proteins is analysed.
      Genomics indicate that spectrin was the first to appear, since the genome of the
      choanoflagellate Monosiga brevicolis contains genes for alpha, beta and betaH
      spectrin. This organism represents a lineage of free-living and colonial protists
      from which the metazoa are considered to have diverged. This indicates that
      spectrin emerged in evolution before the animals. Simple animals such as the
      placozoan Trichoplax adherens also contain recognizable precursors of 4.1,
      ankyrin and adducin, but these could probably not bind spectrin. Ankyrin and
      adducin seem to have acquired spectrin-binding activity with the appearance of
      tissues since they appear to have largely the same domain structure in all
      eumetazoa. 4.1 was adapted more recently, with the emergence of the vertebrates,
      to bind spectrin and promote its interaction with actin. A simple hypothesis is
      that spectrin was prerequisite (but not sufficient) for animal life; that
      spectrin interaction with ankyrin and adducin was required for evolution of major
      tissues; and that 4.1 acquired a spectrin-actin binding activity as animal size
      increased with the appearance of vertebrates. The spectrin/ankyrin/adducin/4.1
      complex represents a remarkable system that underpins animal life; it has been
      adapted to many different functions at different times during animal evolution.

PMID- 20688552
TI  - Neighbouring relations of the posterior ethmoid studied by axial computed
      tomography.
AB  - The anatomy of the paranasal sinuses is variable and it is important to
      appreciate their clinical and surgical significance. During both posterior
      ethmoid and sphenoid sinus surgery, but also for endoscopic approach of
      pituitary, a good knowledge of the anatomy is essential for understanding the
      pathological process and to prevent surgical complications (optic nerve, internal
      carotid artery injury during surgery). Although coronal Computerized Tomography
      (CT) is the routine procedure performed for functional endoscopic sinus surgery
      (FESS), axial CT is most useful in demonstrating the anatomy of the posterior
      ethmoid and the sphenoid sinus. The authors comment the posterior ethmoid cells
      and its variable relationship with the sphenoid sinus and its intimate
      association with the optic nerve, for using a pictorial axial CT by studying 50
      CT head region.

PMID- 20688553
TI  - ST shape classification in ECG by constructing reference ST set.
AB  - Abnormal changes in the ST segment of an electrocardiogram (ECG) are very
      important diagnostic parameters for detecting myocardial ischemia. ST segment
      analysis requires a long-term ECG recording because of the transient change of
      the ST segment. Deviations of the ST segment are generally related to myocardial
      abnormality. In this study, we classify the ST segments by their morphology.
      First, a set of reference ST shapes is given. The ECG analysis algorithm
      developed in this study consists of feature point detection and ST shape
      classification. S wave and J-point detection are performed during the process of
      feature point detection, and the proposed algorithm classifies the STs into
      reference ST shapes. To improve the performance of ST shape classification, the
      rules for the trend of previous beats and the shape type of previous beats are
      used. The results from the proposed algorithm can provide information on the
      change in the ST shape. In our evaluation for classification of STs by their
      morphology using the test ECG data, the global correct rate was 83.14%. The best
      accuracy of existing ST level detection algorithms are 90% and over. However,
      considering that ST level detection algorithms cannot show the change of ST
      morphology; and that there are no studies about the classification of STs by
      their morphology using a reference ST set, the proposed algorithm is worthy of
      note.

PMID- 20688554
TI  - Continuous monitoring of electromyography (EMG), mechanomyography (MMG),
      sonomyography (SMG) and torque output during ramp and step isometric
      contractions.
AB  - In this study we simultaneously collected ultrasound images, EMG, MMG from the
      rectus femoris (RF) muscle and torque signal from the leg extensor muscle group
      of nine male subjects (mean+/-SD, age=30.7+/-.4.9 years; body weight=67.0+/
      8.4kg; height=170.4+/-6.9cm) during step, ramp increasing, and decreasing at
      three different rates (50%, 25% and 17% MVC/s). The muscle architectural
      parameters extracted from ultrasound imaging, which reflect muscle contractions,
      were defined as sonomyography (SMG) in this study. The cross-sectional area (CSA)
      and aspect ratio between muscle width and thickness (width/thickness) were
      extracted from ultrasound images. The results showed that the CSA of RF muscles
      decreased by 7.25+/-4.07% when muscle torque output changed from 0% to 90% MVC,
      and the aspect ratio decreased by 41.66+/-7.96%. The muscle contraction level and
      SMG data were strongly correlated (R(2)=0.961, P=0.003, for CSA and R(2)=0.999,
      P<0.001, for width/thickness ratio). The data indicated a significant difference
      (P<0.05) in percentage changes for CSA and aspect ratio among step, ramp
      increasing, and decreasing contractions. The normalized EMG RMS in ramp
      increasing was 8.25+/-4.00% higher than step (P=0.002). The normalized MMG RMS of
      step contraction was significantly lower than ramp increasing and decreasing,
      with averaged differences of 12.22+/-3.37% (P=0.001) and 12.06+/-3.37% (P=0.001),
      respectively. The results of this study demonstrated that the CSA and aspect
      ratio, i.e., SMG signals, can provide useful information about muscle
      contractions. They may therefore complement EMG and MMG for studying muscle
      activation strategies under different conditions.

PMID- 20688555
TI  - More than health: the added value of health services in remote Scotland and
      Australia.
AB  - Health services are suggested to contribute to remote communities in the ways
      that extend beyond healthcare delivery. This international multiple case-study
      research provides qualitative evidence of the social, economic and human
      contributions (the 'added-value') that may be lost should remote communities lose
      in-situ health provision. We present a typology of added-value contributions that
      differentiates institutional aspects (residing in buildings, or embodied in the
      specific status, capabilities and skills of health professionals) and individual
      aspects (attributable to health professionals' unique personalities and choices).
      This typology has relevance for communities, policymakers and managers when
      considering the impacts of potential service changes.

PMID- 20688556
TI  - Reduced endurance of the cervical flexor muscles in patients with concurrent
      temporomandibular disorders and neck disability.
AB  - Subjects with temporomandibular disorders (TMDs) have been found to have clinical
      signs and symptoms of cervical dysfunction. Although many studies have
      investigated the relationship between the cervical spine and TMD, no study has
      evaluated the endurance capacity of the cervical muscles in patients with TMD.
      Thus the objective of this study was to determine whether patients with TMD had a
      reduced endurance of the cervical flexor muscles at any level of muscular
      contraction when compared with healthy subjects. One hundred and forty-nine
      participants provided data for this study (49 subjects were healthy, 54 had
      myogenous TMD, and 46 had mixed TMD). There was a significant difference in
      holding time at 25% MVC between subjects with mixed TMD when compared to subjects
      with myogenous TMD and healthy subjects. This implies that subjects with mixed
      TMD had less endurance capacity at a lower level of contraction (25% MVC) than
      healthy subjects and subjects with myogenous TMD. No significant associations
      between neck disability, jaw disability, clinical variables and neck flexor
      endurance test were found.

PMID- 20688557
TI  - The Yin and Yang of bone morphogenetic proteins in cancer.
AB  - Bone morphogenetic proteins (BMPs) were first studied as growth factors or
      morphogens of the transforming growth factor-beta superfamily. These growth
      molecules, originally associated with bone and cartilage development, are now
      known to play an important role in morphogenesis and homeostasis in many other
      tissues. More recently, significant contributions from BMPs, their receptors, and
      interacting molecules have been linked to carcinogenesis and tumor progression.
      On the other hand, BMPs can sometimes function as a tumor suppressor. Our report
      highlights these new roles in the pathogenesis of cancer that may suggest novel
      targets for therapeutic intervention.

PMID- 20688558
TI  - Redox extends its regulatory reach to chloroplast protein import.
AB  - The import of chloroplast proteins synthesized in the cytosol of a plant cell is
      mediated by two multiprotein complexes or translocons located at the outer and
      inner membranes of the chloroplast envelope, respectively, TOC and TIC. These
      complexes integrate different signals to assure the timely transport of proteins
      into the chloroplast in accordance with the metabolic and developmental needs of
      the cell. The past few years have witnessed the emergence of redox as a regulator
      of the protein transport process. Here, we discuss evidence that the metabolic
      redox state of the chloroplast regulates the import of preproteins by altering
      either the activity or composition of participating transport components. It
      appears that, through these redox changes, chloroplasts communicate with other
      compartments of the plant cell.

PMID- 20688559
TI  - DRAMMS: Deformable registration via attribute matching and mutual-saliency
      weighting.
AB  - A general-purpose deformable registration algorithm referred to as "DRAMMS" is
      presented in this paper. DRAMMS bridges the gap between the traditional voxel
      wise methods and landmark/feature-based methods with primarily two contributions.
      First, DRAMMS renders each voxel relatively distinctively identifiable by a rich
      set of attributes, therefore largely reducing matching ambiguities. In
      particular, a set of multi-scale and multi-orientation Gabor attributes are
      extracted and the optimal components are selected, so that they form a highly
      distinctive morphological signature reflecting the anatomical and geometric
      context around each voxel. Moreover, the way in which the optimal Gabor
      attributes are constructed is independent of the underlying image modalities or
      contents, which renders DRAMMS generally applicable to diverse registration
      tasks. A second contribution of DRAMMS is that it modulates the registration by
      assigning higher weights to those voxels having higher ability to establish
      unique (hence reliable) correspondences across images, therefore reducing the
      negative impact of those regions that are less capable of finding correspondences
      (such as outlier regions). A continuously-valued weighting function named "mutual
      saliency" is developed to reflect the matching uniqueness between a pair of
      voxels implied by the tentative transformation. As a result, voxels do not
      contribute equally as in most voxel-wise methods, nor in isolation as in
      landmark/feature-based methods. Instead, they contribute according to the
      continuously-valued mutual-saliency map, which dynamically evolves during the
      registration process. Experiments in simulated images, inter-subject images,
      single-/multi-modality images, from brain, heart, and prostate have demonstrated
      the general applicability and the accuracy of DRAMMS.

PMID- 20688560
TI  - Pattern-based sensing with simple metal-dye complexes.
AB  - Different strategies for the creation of optical sensors with metal-dye complexes
      are discussed. The focus is on sensors, which are used in conjunction with
      pattern recognition protocols. It is shown that remarkably powerful sensors can
      be obtained by combining commercially available dyes with simple transition metal
      complexes.

PMID- 20688561
TI  - Spectroscopic, solvent influence and thermal studies of ternary copper(II)
      complexes of diester and dinitrogen base ligands.
AB  - New mixed-ligand copper(II) complexes containing the bidentate dinitrogen ligands
      [N,N,N',N'-tetramethylethylenediamine (tmen), 2,2'-bipyridine (bipy) and 1,10
      phenanthroline (phen)] and the bidentate dioxygen ligands [diethylmalonate (DEM),
      ethylacetoacetate (EAA) and ethylbenzoylacetate (EBA)] were prepared. The
      complexes were characterized by elemental analysis, infrared, mass and ESR
      spectral data, magnetic and molar conductance measurements and thermal
      gravimetric analysis. From the investigation, the geometries of the complexes are
      square planar for perchlorate complexes and a square pyramid or octahedral for
      the nitrate complexes. Solvatochromic behavior of the Cu(II) complexes indicates
      strong solvatochromism of their solutions in polar and non-polar solvents. The
      observed solvatochromism is due to the solute-solvent interaction between the
      chelate cation and the solvent molecules.

PMID- 20688562
TI  - Time-variant analysis of phase couplings and amplitude-frequency dependencies of
      and between frequency components of EEG burst patterns in full-term newborns.
AB  - OBJECTIVE: Burst activity of the 'trace alternant' (TA) EEG pattern in the quiet
      sleep of full-term newborns is investigated to explore the timing and the time
      variant coupling characteristics of and between a burst's oscillatory components.
      The working hypothesis is that signal properties provide information about the
      neuronal initiation processes of the burst, and about the coupling and
      interrelation dynamics between cortical low-frequency oscillations and high
      frequency spindles in thalamic structures which substantially contribute to the
      burst pattern. METHODS: For time-variant phase-locking index (PLI), phase
      synchronization index (PSI), quadratic phase coupling (QPC) measures, and
      amplitude-frequency dependency analyses the Gabor and the Hilbert transformation,
      both implemented as fast Fourier transformation-based approaches, were used.
      Additionally, models of mutually coupled Duffing oscillators were adapted to the
      burst data derived from the neonates ('measured bursts'), and the corresponding
      'modeled burst' simulations were analyzed in comparison to the measured bursts.
      RESULTS: A strong phase-locking of the high-frequency oscillations and
      synchronization between low- and high-frequency oscillatory activity at burst
      onset can be observed. The QPC courses and the amplitude of all oscillations rise
      slightly before or at the burst onset and reach their maximum within the
      following 1-3 s after onset. Additionally, correlative envelope-envelope and
      envelope-frequency couplings within and between the burst oscillations can be
      demonstrated. All theses time-variant signal properties can be simulated by the
      model. CONCLUSIONS: The amplitude-independent phase measures point to a phase
      stabilization of high-frequency oscillatory activity which occurs before the
      initiation of the low-frequency oscillation. This finding points to a trigger
      process in which the thalamus is initially involved. After burst onset the
      cortical low-frequency oscillation modulates the high-frequency oscillatory
      activities, where modulation and additional coupling effects can be explained by
      three mutually coupled oscillators. SIGNIFICANCE: The model-based analysis
      strategy offers an up-to-date methodological guideline and sets a new standard of
      analysis for the investigation of EEG patterns and event-related potentials.

PMID- 20688563
TI  - Rapid and multiple in situ identification and analyses of physiological status of
      specific bacteria based on fluorescent in situ hybridization.
AB  - Quantitative analysis of the target microorganism in microbial communities is
      important for the assessment of bacterial activity in environment. Here we
      present a method of a combination of fluorescent in situ hybridization (FISH)
      method and live/dead staining which allows in situ identification and analysis of
      physiological status of specific bacteria.

PMID- 20688564
TI  - Hepatitis B virus infection and risk of non-Hodgkin lymphoma in South Korea: a
      cohort study.
AB  - BACKGROUND: Hepatitis B virus (HBV) infection is common throughout Asia and
      Africa. Whether chronic HBV infection increases risk of non-Hodgkin lymphoma
      (NHL) is unclear. We aimed to assess the association between chronic HBV
      infection and subsequent development of NHL in a South Korean cohort. METHODS:
      The Korean Cancer Prevention Study is a cohort study of South Korean workers and
      their dependants enrolled during 1992-95. From this cohort, we excluded
      individuals who died before Jan 1, 1993, who had cancer at or before the initial
      visit, who had missing information about weight, height, alanine aminotransferase
      or aspartate aminotransferase concentrations, or alcohol use, or who had evidence
      of HIV or HCV infection. Of 1,284,586 eligible participants, 603,585 had baseline
      data for serum hepatitis B surface antigen (HBsAg) status and were included in
      our study. We regarded HBsAg positivity at baseline as evidence of chronic HBV
      infection. Participants were followed up from baseline until Dec 31, 2006. We
      used national databases of inpatient and outpatient diagnoses and mortality
      records to ascertain occurrence of haematological malignancies. We assessed
      incidence of NHL overall and of NHL subtypes, malignant immunoproliferation,
      Hodgkin's lymphoma, multiple myeloma, and various leukaemias. We used Cox
      regression to evaluate associations with HBsAg status, adjusting for sex, age,
      and enrolment year. FINDINGS: 53,045 (9%) of 603,585 participants tested positive
      for HBsAg at baseline. Subsequently, 133 HBsAg-positive and 905 HBsAg-negative
      individuals developed NHL. HBsAg-positive participants had an increased risk of
      NHL overall compared with those who were HBsAg-negative (incidence 19.4 vs 12.3
      per 100,000 person-years; hazard ratio [HR] 1.74, 95% CI 1.45-2.09, adjusted for
      sex, age at baseline, and enrolment year). Among NHL subtypes, HBsAg positivity
      was associated with increased risk of diffuse large B-cell lymphoma (n=325,
      incidence 6.86 vs 3.79 per 100,000 person-years; adjusted HR 2.01, 1.48-2.75) and
      other or unknown subtypes (n=591, incidence 10.5 vs 7.07 per 100,000 person
      years; adjusted HR 1.65, 1.29-2.11), compared with HBsAg negativity. Increased
      risk was also recorded for malignant immunoproliferation (n=14, incidence 0.44 vs
      0.15 per 100,000 person-years; adjusted HR 3.79, 1.05-13.7). Risk of these
      malignancies was consistently raised in HBsAg-positive participants throughout 14
      years of follow-up. HBsAg positivity was not associated with follicular or T-cell
      NHL, Hodgkin's lymphoma, multiple myeloma, or various leukaemias. INTERPRETATION:
      During extended follow-up, HBsAg-positive individuals had an increased risk of
      NHL, suggesting that chronic HBV infection promotes lymphomagenesis. FUNDING:
      Korean Seoul City Research and the National Research and Development Program for
      Cancer Control, Ministry for Health, Welfare and Family Affairs, Republic of
      Korea; US National Cancer Institute.

PMID- 20688565
TI  - HBV infection as a risk factor for non-Hodgkin lymphoma.

PMID- 20688567
TI  - Embryo aneuploidy and the role of morphological and genetic screening.
AB  - Chromosome abnormalities are common among human oocytes and are usually lethal to
      any embryos they produce. It therefore seems logical that a reliable technique
      for distinguishing between normal and aneuploid embryos would be a useful tool
      for physicians and embryologists, assisting the choice of which embryo(s) to
      prioritize for uterine transfer. This concept has led to the development of a
      variety of methods for the detection of chromosome abnormalities in oocytes and
      embryos, most often referred to as preimplantation genetic screening (PGS).
      However, several well-controlled studies have been unable to show an advantage of
      chromosome screening in terms of pregnancy and birth rates. Some investigators
      have suggested that damage to embryos, sustained during cleavage-stage biopsy,
      might explain why PGS has not always provided the anticipated benefits. This
      paper asks whether there is evidence that a non-invasive, morphological analysis
      could allow chromosomally normal embryos to be accurately identified and reviews
      data from the most recent publication concerning IVF outcome following PGS.

PMID- 20688566
TI  - The Norrin/Frizzled4 signaling pathway in retinal vascular development and
      disease.
AB  - Disorders of retinal vascular growth and function are responsible for vision loss
      in a variety of diseases, including diabetic retinopathy, age-related macular
      degeneration, retinopathy of prematurity and retinal artery or vein occlusion.
      Over the past decade, a new signaling pathway that controls retinal vascular
      development has emerged from the study of inherited disorders - in both humans
      and mice - that are characterized by retinal hypovascularization. This pathway
      utilizes a glial-derived extracellular ligand, Norrin, that acts on a
      transmembrane receptor, Frizzled4, a coreceptor, Lrp5, and an auxiliary membrane
      protein, Tspan12, on the surface of developing endothelial cells. The resulting
      signal controls a transcriptional program that regulates endothelial growth and
      maturation. It will be of great interest to determine whether modulating this
      pathway could represent a therapeutic approach to human retinal vascular disease.

PMID- 20688568
TI  - Management of endometrioma prior to IVF: compliance with ESHRE guidelines.
AB  - Management of endometrioma before IVF remains controversial. As well as some
      measurable benefits from surgical treatment, there are also potential risks that
      should be discussed with the patients to help them make an informed decision.
      When surgery is compared with expectant management, there appear to be no
      statistically significant differences in pregnancy rate and ovarian response to
      exogenous stimulation. The objectives of this European Society of Human
      Reproduction and Embryology (ESHRE)-sponsored survey were to acquire knowledge of
      current strategies for the management of endometrioma (>3 cm) prior to IVF and to
      explore adherence to ESHRE guidelines. A validated, peer-reviewed online
      questionnaire made of 14 questions was sent to 396 members of the ESHRE Special
      Interest Groups (Reproductive Surgery and Endometriosis/Endometrium), with a
      response rate of 27%. Surgical management is the most common treatment (82.2%),
      with drainage and excision of the cyst wall being the preferred surgical approach
      (78.5%). Monthly depot gonadotrophin-releasing hormone analogues are the
      preferred choice of medical treatment of endometriomas before IVF, with an
      average duration of treatment of 3 months. The findings demonstrate that surgery
      remains the commonest treatment offered for women with endometrioma before IVF.
      This is in line with the recommendations of the ESHRE guidelines.

PMID- 20688570
TI  - Prevention of intra-peritoneal adhesions in gynaecological surgery: theory and
      evidence.
AB  - Post-operative adhesions are a significant complication of all abdominal surgical
      procedures. The major strategies for adhesion prevention in gynaecological
      surgery are focused on the optimization of surgical technique and use of anti
      adhesive agents, which fall into two main categories: pharmacological agents and
      barriers. Surgical technique that minimizes peritoneal trauma can reduce, but
      cannot prevent post-operative adhesion formation. Various local and systemic
      drugs that can alter the local inflammatory response, inhibit the coagulation
      cascade and promote fibrinolysis have been evaluated. Limited data support the
      administration of post-operative corticosteroids in addition to systemic intra
      operative corticosteroids for the prevention of adhesions after gynaecological
      surgery. None of the remaining pharmacological agents have been found effective
      for the reduction of post-operative adhesions. Barriers are currently considered
      the most useful adjuncts, which may reduce adhesion formation. They act by
      separating the traumatized peritoneal surfaces during the healing period. The
      separation can be achieved by solid barriers or fluids. There is limited evidence
      from randomized clinical trials that support the beneficial effect of most of
      these barrier agents in the prevention of intra-peritoneal adhesions after
      gynaecological surgery. However, the evidence is not adequate for definite
      conclusions to be drawn and further research in this field is warranted.

PMID- 20688571
TI  - High serum oestradiol concentrations in IVF cycles increase the risk of pregnancy
      complications related to abnormal placentation.
AB  - The study was designed to evaluate the isolated effect of high serum oestradiol
      concentration on human chorionic gonadotrophin (HCG) day in IVF cycles on
      endometrial receptivity and placentation. A retrospective cohort included all
      women attending the IVF unit in 2006 and 2007, with the best prognosis to achieve
      pregnancy: age (<38 years), less than three IVF cycles, transfer of two highest
      grade embryos and no evidence of factors known to impair implantation or that are
      associated with increased risk of pregnancy complications. The total included 280
      patients were categorized into three groups according to their serum oestradiol
      concentration on HCG day: group 1, oestradiol <5000 pmol/l, group 2, oestradiol
      in the range 5000-10,000 pmol/l and group 3, oestradiol in the range of 10,000
      15,000 pmol/l. No significant differences were found between the groups in
      implantation, pregnancy and abortion rates. The high oestradiol group was
      characterized by high rate (20.8%) of pregnancy complications related to abnormal
      placentation--fetal growth restriction, pregnancy-induced hypertension and
      abnormal implantation of the placenta. Hence, the decision to perform embryo
      transfer in high-responder patients should take into consideration both possible
      risks of ovarian hyperstimulation syndrome and pregnancy complications related to
      abnormal placentation.

PMID- 20688572
TI  - Knowledge deficits regarding Chagas disease may place Mexico's blood supply at
      risk.
AB  - Prevention of transfusion-related Chagas disease in Mexico City depends on
      targeted questionnaire-based screening of donors by nurses at blood banks. To
      assess potential problems with this strategy, surveys were distributed to the
      nurses who screen donors in a random sampling of nine blood banks in Mexico City,
      to measure appropriate knowledge about Chagas disease. We found that 80% (95% CI
      68-92%) of nurses answered at least one of the three donor risk factor questions
      incorrectly, which may fail to trigger confirmatory laboratory testing of
      potentially infected units. If this knowledge deficit is widespread, up to
      680,000 units (95% CI 578,000-782,000 units) of donated blood could be
      potentially contaminated with Chagas disease in Mexico. In place of targeted
      screening, routine laboratory testing of all donated blood would be a cost
      effective method to safeguard blood recipients from iatrogenic Chagas disease.

PMID- 20688573
TI  - Vitamin B supplements for prevention of stroke.

PMID- 20688575
TI  - Recertification and continuing professional development: The way ahead.
AB  - The arguments in favour of recertification have been made cogently. Doctors in
      the UK on the whole continue to enjoy the trust and respect of their patients and
      the general public, but the Shipman enquiry led by Dame Janet Smith questioned
      the validity of the existing system. Following a lengthy discussion, the Chief
      Medical Officer of England published his proposal for professional regulation:
      Trust, assurance and safety - the regulation of health professionals in the 21st
      century1 was published in February 2007. This document laid out the principles of
      revalidation for all doctors practising in the United Kingdom. The purpose of
      revalidation is principally to ensure that doctors update their knowledge and
      skills, and that they are fit to practise. This mechanism of revalidation will
      ensure that health professionals will be able to demonstrate their continued
      fitness to practise by collecting supporting data. The medical revalidation has
      two components: relicensure and specialist recertification. From 16 November 2009
      all doctors are expected to have a licence to practise to enable them to remain
      on the Medical Register, and this licence must be renewed every year. This
      process will be managed by the General Medical Council (GMC). Recertification
      will apply to all specialist doctors, including general practitioners, requiring
      them to demonstrate that they meet the standards that apply to their particular
      medical specialty. The Royal Colleges have been delegated to set these standards,
      and approved by the GMC. Recertification will take place every five years.
      Recertification will be underpinned by enhanced appraisal, multi source feedback,
      and a robust continuing professional development programme.

PMID- 20688576
TI  - Catechol O-methyltransferase haplotype predicts immediate musculoskeletal neck
      pain and psychological symptoms after motor vehicle collision.
AB  - Genetic variations in the catechol-O-methyltransferase (COMT) gene have been
      associated with experimental pain and risk of chronic pain development, but no
      studies have examined genetic predictors of neck pain intensity and other patient
      characteristics after motor vehicle collision (MVC). We evaluated the association
      between COMT genotype and acute neck pain intensity and other patient
      characteristics in 89 Caucasian individuals presenting to the emergency
      department (ED) after MVC. In the ED in the hours after MVC, individuals with a
      COMT pain vulnerable genotype were more likely to report moderate-to-severe
      musculoskeletal neck pain (76 versus 41%, RR = 2.11 (1.33-3.37)), moderate or
      severe headache (61 versus 33%, RR = 3.15 (1.05-9.42)), and moderate or severe
      dizziness (26 versus 12%, RR = 1.97 (1.19-3.21)). Individuals with a pain
      vulnerable genotype also experienced more dissociative symptoms in the ED, and
      estimated a longer time to physical recovery (median 14 versus 7 days, P = .002)
      and emotional recovery (median 8.5 versus 7 days, P = .038). These findings
      suggest that genetic variations affecting stress response system function
      influence the somatic and psychological response to MVC, and provide the first
      evidence of genetic risk for clinical symptoms after MVC. PERSPECTIVE: The
      association of COMT genotype with pain symptoms, psychological symptoms, and
      recovery beliefs exemplifies the pleiotropic effects of stress-related genes,
      which may provide the biological substrate for the biopsychosocial model of post
      MVC pain. The identification of genes associated with post-MVC symptoms may also
      provide new insights into pathophysiology.

PMID- 20688577
TI  - Definitive 125I prostate brachytherapy implant for low-risk prostate cancer in a
      patient with an ileal pouch-anal anastomosis: a case report.
AB  - PURPOSE: To report on the safe and effective use of a prostate brachytherapy
      implant for clinically low-risk prostate cancer in a patient with previous ileal
      pouch-anal anastomosis. METHODS AND MATERIALS: A patient with a previous history
      of total proctocolectomy with ileal pouch-anal anastomosis was diagnosed with low
      risk prostate cancer. He underwent prostate brachytherapy implant and his
      urinary, bowel, and sexual function were monitored preoperatively and regularly
      after his implant. RESULTS: Approximately 1-year postimplant, the patient's serum
      prostate-specific antigen continued to decrease and urinary obstructive symptoms
      measured via a standardized patient-reported instrument increased transiently but
      returned to baseline. His sexual function remains slightly diminished. His self
      reported bowel function has been essentially unchanged, and he specifically
      denies increased stool frequency, urgency, incontinence, tenesmus, or
      hematochezia. CONCLUSIONS: Prostate brachytherapy appears to be both safe and
      effective for treating low-risk prostate cancer in patients with a pre-existing
      ileal pouch-anal anastomosis. Although there is a potential for significant late
      injury to the neorectum, a previous small series indicated that this had not been
      seen. Models currently used to predict normal tissue complication probabilities
      do not seem well applied to this case. The developments of algorithms that more
      correctly model this condition are encouraged.

PMID- 20688578
TI  - Predictors of remission of type 2 diabetes mellitus after laparoscopic gastric
      banding and bypass.
AB  - BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with obesity and
      results in considerable morbidity and mortality. Our objectives were to evaluate
      the effect of laparoscopic bariatric surgery on the control of T2DM in morbidly
      obese patients in a U.K. population and to determine the predictors of T2DM
      remission after bariatric surgery. The study was performed at teaching university
      hospitals and affiliated private hospitals. METHODS: Of 487 patients who
      underwent laparoscopic bariatric procedures from 2002 to 2007, 74 patients
      (15.2%) had established T2DM. The results are presented as the mean values.
      Multivariate analysis was used to identify the factors predictive of remission of
      T2DM after bariatric surgery. RESULTS: The body mass index before laparoscopic
      gastric bypass (LGB; n = 48) and laparoscopic adjustable gastric banding (LAGB; n
      = 26) were comparable (52 versus 51 kg/m(2), P = .508). At a mean follow-up of
      16.9 months, 41% had remission and 59% had experienced improvement in T2DM.
      Although the duration of follow-up was significantly longer for the patients who
      had undergone LAGB than for those who had undergone LGB (23 versus 13.4 months, P
      = .001), the percentage of excess weight loss (%EWL) was significantly greater
      after LGB than after LAGB (59.4% versus 48.8%, P = .031), with an associated
      greater remission rate of T2DM (50% versus 24%, P = .034). Multivariate analysis
      revealed a greater %EWL and younger age to be independent predictors of
      postoperative remission of T2DM, and LGB, longer follow-up, and female gender
      were independent predictors of a greater %EWL. CONCLUSION: The %EWL was the only
      predictor of remission of T2DM that was influenced by the choice of bariatric
      procedure. In our study, LGB offered greater weight loss and a chance of
      remission of T2DM compared with LAGB and within 2 years of surgery.

PMID- 20688579
TI  - Creating a credential for bariatric behavioral health professionals: potential
      benefits, pitfalls, and provider opinion.
AB  - BACKGROUND: Since the 1991 recommendation by the National Institutes of Health
      sponsored consensus development conference, preoperative psychosocial evaluation
      of weight loss surgery patients has been adopted by >80% of weight loss surgery
      programs. Although some published suggestions for conducting evaluations exist,
      no formal guidelines have been published specifying the qualifications, content
      knowledge, or clinical experience for the behavioral health professionals who
      conduct them. As a result, the backgrounds of behavioral health professionals
      working with bariatric surgery patients are varied, and no mechanism exists to
      ensure consistent quality of care. To obtain expert opinion on this issue, a
      survey of the American Society for Metabolic and Bariatric Surgery membership was
      conducted using an Internet-based survey. METHODS: American Society for Metabolic
      and Bariatric Surgery members of all disciplines were invited by electronic mail
      to complete an Internet-based survey. Separate forms were created for behavioral
      health providers and for members of other disciplines. RESULTS: A total of 409
      American Society for Metabolic and Bariatric Surgery members responded (60
      behavioral health and 349 nonbehavioral health). Of the 409 respondents, 95%
      indicated a belief that it is important for behavioral health providers to have
      specialty knowledge; 87% indicated a belief that specialty experience is
      important; and 70.6% favored the development of a specialty credential for
      bariatric behavioral health providers to regulate the quality of patient care.
      However, the respondents also reported concerns about creating such a credential.
      CONCLUSION: Our results reflect widespread opinion that the provision of
      bariatric behavioral health services requires specialty knowledge and experience
      and that a credentialing system would help regulate the standard of care in the
      field. However, some concerns about credential development remain.

PMID- 20688580
TI  - Tumor growth factor expression in obesity and changes in expression with weight
      loss: another cause of increased virulence and incidence of cancer in obesity.
AB  - BACKGROUND: Obesity is associated with increased tumorigenesis. Previously, we
      demonstrated that inflammation in obesity caused cancer fighting cells to display
      greater surface receptor levels, predisposing them to early cell death. We
      measured the inflammatory tumor growth factor levels to determine whether
      inflammation in obesity increases expression of these factors, potentially
      predisposing these patients to greater rates of neoplasia. METHODS: A total of 24
      patients undergoing weight loss surgery had samples collected preoperatively and
      at 6 and 12 months after surgery. The growth factors analyzed included tumor
      necrosis factor (TNF)-alpha, granulocyte-macrophage colony-stimulating factor,
      interferon-gamma, interleukin (IL)-1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10,
      vascular endothelial growth factor, hepatocyte growth factor, TNF-receptor I (TNF
      RI), TNF-RII, death receptor 5, leptin, and adiponectin. Control samples were
      obtained from 10 healthy, normal weight volunteers. RESULTS: The tumor growth
      factors TNF-alpha, TNF-RI, TNF-RII, vascular endothelial growth factor,
      hepatocyte growth factor, interferon-gamma, IL-2, IL-5, and IL-6 all decreased
      significantly (P <.05) compared with the preoperative values. The IL-4, IL-8,
      leptin, death receptor 5, adiponectin, and granulocyte-macrophage colony
      stimulating factor levels did not change significantly over time. The IL-1b and
      IL-10 levels were less than the detection limit at all points. When obese patient
      serum was compared with healthy volunteer pooled serum, we found that the leptin,
      death receptor 5, hepatocyte growth factor, vascular endothelial growth factor,
      TNF-RI, TNF-RII, TNF-alpha, IFN-gamma, granulocyte-macrophage colony-stimulating
      factor, IL-4, IL-5, IL-6, and IL-8 levels were all 2-37 times greater than the
      levels in the controls at baseline. The concentrations of these same growth
      factors had decreased levels only 1-3.5 times greater than those of the controls
      at 12 months postoperatively. CONCLUSION: Many inflammatory tumor growth factors
      are present in greater concentrations in obese individuals. This could explain
      the greater prevalence of neoplasia in the morbidly obese population.

PMID- 20688574
TI  - B vitamins in patients with recent transient ischaemic attack or stroke in the
      VITAmins TO Prevent Stroke (VITATOPS) trial: a randomised, double-blind,
      parallel, placebo-controlled trial.
AB  - BACKGROUND: Epidemiological studies suggest that raised plasma concentrations of
      total homocysteine might be a risk factor for major vascular events. Whether
      lowering total homocysteine with B vitamins prevents major vascular events in
      patients with previous stroke or transient ischaemic attack is unknown. We aimed
      to assess whether the addition of once-daily supplements of B vitamins to usual
      medical care would lower total homocysteine and reduce the combined incidence of
      non-fatal stroke, non-fatal myocardial infarction, and death attributable to
      vascular causes in patients with recent stroke or transient ischaemic attack of
      the brain or eye. METHODS: In this randomised, double-blind, parallel, placebo
      controlled trial, we assigned patients with recent stroke or transient ischaemic
      attack (within the past 7 months) from 123 medical centres in 20 countries to
      receive one tablet daily of placebo or B vitamins (2 mg folic acid, 25 mg vitamin
      B6, and 0.5 mg vitamin B12). Patients were randomly allocated by means of a
      central 24-h telephone service or an interactive website, and allocation was by
      use of random permuted blocks stratified by hospital. Participants, clinicians,
      carers, and investigators who assessed outcomes were masked to the assigned
      intervention. The primary endpoint was the composite of stroke, myocardial
      infarction, or vascular death. All patients randomly allocated to a group were
      included in the analysis of the primary endpoint. This trial is registered with
      ClinicalTrials.gov, NCT00097669, and Current Controlled Trials, ISRCTN74743444.
      FINDINGS: Between Nov 19, 1998, and Dec 31, 2008, 8164 patients were randomly
      assigned to receive B vitamins (n=4089) or placebo (n=4075). Patients were
      followed up for a median duration of 3.4 years (IQR 2.0-5.5). 616 (15%) patients
      assigned to B vitamins and 678 (17%) assigned to placebo reached the primary
      endpoint (risk ratio [RR] 0.91, 95% CI 0.82 to 1.00, p=0.05; absolute risk
      reduction 1.56%, -0.01 to 3.16). There were no unexpected serious adverse
      reactions and no significant differences in common adverse effects between the
      treatment groups. INTERPRETATION: Daily administration of folic acid, vitamin B6,
      and vitamin B12 to patients with recent stroke or transient ischaemic attack was
      safe but did not seem to be more effective than placebo in reducing the incidence
      of major vascular events. These results do not support the use of B vitamins to
      prevent recurrent stroke. The results of ongoing trials and an individual patient
      data meta-analysis will add statistical power and precision to present estimates
      of the effect of B vitamins. FUNDING: Australia National Health and Medical
      Research Council, UK Medical Research Council, Singapore Biomedical Research
      Council, Singapore National Medical Research Council, Australia National Heart
      Foundation, Royal Perth Hospital Medical Research Foundation, and Health
      Department of Western Australia.

PMID- 20688581
TI  - Total gastrectomy for failed treatment with endotherapy of chronic
      gastrocutaneous fistula after sleeve gastrectomy.

PMID- 20688582
TI  - Acute postgastric reduction surgery neuropathy and severe malnutrition after
      sleeve gastrectomy for morbid obesity.

PMID- 20688583
TI  - Determination of ticagrelor and two metabolites in plasma samples by liquid
      chromatography and mass spectrometry.
AB  - Rapid and sensitive analytical methods using liquid chromatography with tandem
      mass spectrometry (LC/MS/MS) were developed for the determination of ticagrelor,
      the first reversible oral platelet P2Y(12) receptor inhibitor, and its
      metabolites AR-C124910XX and AR-C133913XX in human plasma. Ticagrelor and its
      metabolites were extracted using protein precipitation with acetonitrile.
      Chromatographic separations were performed on reversed phase columns and
      detection using atmospheric pressure chemical ionization (APCI). Ticagrelor and
      AR-C124910XX were analyzed in the same assay, with the internal standard, d7
      ZD6140, on a C18 column using negative ionization; AR-C133913XX analyzed
      separately on a phenyl column using positive ionization. Full validation of the
      methods was performed including selectivity, lower limit of quantification,
      accuracy, precision stability and incurred sample reproducibility and incurred
      sample stability. Total analytical run time was short (2 min). Calibration curves
      were established in the range 5-5000ng/mL for ticagrelor, 2.5-2500 ng/mL for AR
      C124910XX and 2-1000 ng/mL for AR-C133913XX. Lower limits of quantification for
      ticagrelor, AR-C124910XX and AR-C133913XX were determined to be 5, 2.5 and 2.0
      ng/mL, respectively from 100 microL of human plasma. For ticagrelor, AR-C124910XX
      and AR-C133913XX, mean intra-batch accuracy was 91.9-109.0%, 86.8-109.2% and
      100.5-112.0%, respectively; intra-batch precision was 4.0-8.4%, 5.2-16.9% and 3.9
      12.3%, respectively. The methods were also applied to quantification of
      ticagrelor, AR-C124910XX and AR-C133913XX in rabbit, rat, mouse and marmoset,
      using 25 microL of animal plasma. A modified methodology was developed to
      quantify ticagrelor and AR-C124910XX in plasma from dog and cynomolgus monkey.
      Human incurred samples were found to generate consistent reproducibility and
      stability results. This method was successfully applied to determine plasma
      concentrations following administration of ticagrelor in human volunteers and
      patients, and animal safety evaluation studies. This validated methods has the
      advantages of being straightforward, robust and allows a fast throughput of
      samples.

PMID- 20688585
TI  - [Should the treatment of diabetic dyslipidemia be modified after the Action to
      Control Cardiovascular Risk in Diabetes Lipid study?].

PMID- 20688584
TI  - Primitive origins of prostate cancer: in vivo evidence for prostate-regenerating
      cells and prostate cancer-initiating cells.
AB  - Tissue stem cells have been linked to cancers of epithelial origin including the
      prostate. There are three relevant issues concerning stem cells and cancer that
      rely solely on functional studies: 1. Are there tissue-regenerating stem cells in
      the adult organ? 2. Can tissue-regenerating cells serve as targets for
      transformation? 3. Do primary tumors contain tumor-propagating (cancer stem)
      cells? We will review the recent literature with respect to these critical issues
      to provide a direct link between primitive cells and prostate cancer.

PMID- 20688586
TI  - The intelligent, painless, "germ-free" colonoscopy: A Columbus' egg for
      increasing population adherence to colorectal cancer screening?
AB  - Colorectal cancer (CRC) represents a major cause of morbidity and mortality.
      Although it is widely accepted that CRC screening in average risk populations
      lowers CRC incidence and mortality, a disappointedly low adherence rate to both
      faecal occult blood testing and colonoscopy-based screening programs has been
      observed in Italy and in other European countries. Main reasons for the low
      acceptance of colonoscopy-based CRC screening has been ascribed to lack of
      recommendations given by general practitioners, fear of discomfort or
      complications, embarrassment, and avoidance of unpleasant preparation. New
      advances in endoscopic technology such as colon capsule and robotic colonoscopy
      might represent the ideal tool for CRC screening since they reduce or eliminate
      procedure-related pain and discomfort. Moreover, no disinfection between
      procedures is required. Motion of the new probes along the gastrointestinal tract
      is achieved either in passive modality by utilizing the gut peristalsis (colon
      capsule) or in active "intelligent" modality by means of computer-assisted
      propulsion (robotic colonoscopy). In this review, the preliminary clinical
      results obtained with the new devices are summarized. It is expected that the new
      instruments will be soon available in clinical practice with the hope of
      increasing adherence to CRC screening programs.

PMID- 20688587
TI  - CD133+ stem cell mobilization after partial hepatectomy depends on resection
      extent and underlying disease.
AB  - BACKGROUND: Bone marrow stem cells (BMSC) can participate to liver regeneration.
      However, conflicting results have been reported on this topic in patients
      undergoing liver resection. AIMS: To assess the impact of liver resection extent
      and presence of underlying liver disease in modulating BMSC mobilization.
      METHODS: We enrolled 29 patients undergoing liver resection of different extents,
      5 surgical controls and 10 blood donors. Circulating CD133+ BMSC were measured by
      flow cytometry at different time-points after surgery. The hepatic commitment of
      mobilized BMSC was investigated by polymerase chain reaction. Liver specimens
      were collected during surgery for histopathological analysis. Hepatocyte growth
      factor and granulocyte-colony stimulating factor serum levels were measured by
      enzyme-linked immunosorbent assay. RESULTS: BMSC mobilization was found in
      patients undergoing major liver resection, especially in the presence of
      underlying disease. Ductular reactions were noted in patients with chronic
      hepatopathy and the hepatic progenitor-like cells expressed CD133, NCAM,
      cytokeratin-19, and alpha-fetoprotein. Hepatocyte growth factor and granulocyte
      colony stimulating factor levels increased following liver resection and the
      contemporaneous presence of liver disease was associated with their highest
      raise. CONCLUSIONS: Liver repair is mainly an endogenous process. BMSC become
      important in case of extensive resection, especially in the presence of
      underlying hepatopathy and hepatic progenitor-like cells activation. Hepatocyte
      growth factor and granulocyte-colony stimulating factor seem to be involved in
      the dynamics underlying hepatic regeneration and BMSC recruitment.

PMID- 20688588
TI  - [Importance of anamnesis in the diagnosis of urinary schistosomiasis].

PMID- 20688589
TI  - [Social disparities in the prevalence of overweight and obesity in adolescents].
AB  - INTRODUCTION: Many social factors have a role in determining the risk of
      overweight/obesity in children and adolescents, and are the main barriers in
      their management. This study tries to define the effect that some familial and
      social factors have on the risk of overweight/obesity in children and
      adolescents. METHOD: Population sample of 11- and 14-years old children recruited
      in three Primary Care Centres in Palencia. Their weight, height and skin folds
      were measured, and information gathered about sport activities, TV watching, and
      parental data (weight, height, educational status and occupation). Multivariate
      models were used to analyse the effect of these variables on the weight status
      and on the body fat. RESULTS: Three hundred and twenty-two children were
      included. Prevalence of obesity was 5.6% and that of any degree of overweight was
      28.9%. Overweight was not related to educational status or occupation, but it was
      more often found in males (OR 2.07; 95% CI; 1.12-3.83), in children whose father
      (OR 2.18; 95% CI; 1.14-4.15) or mother (OR 2.17; 95% CI; 1.18-3.98) were
      overweight, and in those who spent >=2 h daily watching TV (OR 2.72; 95% CI; 1.43
      5.19), and it was less frequent in 14 than in 11-year old children (OR 0.42; 95%
      CI; 0.23-0.78). Obesity was only related to a low educational level (OR 19.45;
      95% CI; 1.95-193.82). CONCLUSIONS: Overweight is related with genetic
      environmental factors and the modern society way of life, and occurs across the
      whole social spectrum. But obesity is strongly related to a low educational
      status of the family, and it still is a marker for health disparities.

PMID- 20688590
TI  - Evaluation of the Goldman tip procedure and suture technique in tip rhinoplasty.
AB  - BACKGROUND: The nasal tip is one of the most important features of facial
      aesthetics and its modification is still a great challenge in rhinoplasty. The
      aim of this study was to evaluate outcomes of the Goldman tip procedure and
      suture technique on the shape of the nasal tip. PATIENTS AND METHODS: In a
      randomised clinical trial, 100 primary rhinoplasty patients were enrolled in two
      groups. One group underwent tip rhinoplasty by the Goldman tip procedure and the
      other one by suturing of cartilages. Rhinoplasty outcomes were evaluated after 12
      months. RESULTS: On a 0-100 scale, postoperative patient satisfaction in the
      Goldman and suture groups improved, on average, by 49.16 and 23.12, respectively
      (P < 0.001). In objective assessments on a -8 to +8 scale, the mean of changes
      for the Goldman technique was +3.30 and for the suture technique, +1.18 (P <
      0.001). There was no difference between the two techniques in terms of
      complications. There was a correlation between subjective and objective
      assessments in the suture technique group (P < 0.001, rho = 0.519). CONCLUSION:
      This study has shown that despite the efficacy of both techniques, the Goldman
      tip technique was associated with better results in terms of patient satisfaction
      and objective evaluations.

PMID- 20688591
TI  - Genetic polymorphisms of glutathione S-transferase genes and susceptibility to
      colorectal cancer: a case-control study in an Indian population.
AB  - BACKGROUND: Susceptibility to sporadic colorectal cancer is multifactorial and
      arises from interactive combinations of allelic variants in low-penetrance genes
      and relevant environmental risk factors. Genetic polymorphisms in metabolic
      enzymes as gene susceptibility factors may modify colorectal cancer risk. We
      evaluated the risk of colorectal cancer associated with respective or combined
      glutathione S-transferase (GST) polymorphisms and assessed the interactions
      between genes and environmental factors in a case-control study in an Indian
      population. METHODS: The study included 59 colon and 243 rectal cancer cases, and
      291 cancer-free healthy controls. GST genotypes were detected by multiplex PCR
      based and PCR-RFLP methods. The risk of cancer associated with GST polymorphisms
      was estimated by calculation of odds ratios (ORs) and confidence intervals (95%
      CIs) using unconditional logistic regression. RESULTS: The GSTM1 null genotype
      was found to be associated with a significantly increased rectal cancer risk
      (OR=1.55; 95% CI, 1.05-2.30), while the GSTT1 null genotype with a greater risk
      of colon cancer (OR=2.15; 95% CI, 1.04-4.32). A substantial increase of both
      colon (OR=10.81; 95% CI, 1.11-107.22) and rectal (OR=4.80; 95% CI, 0.94-35.91)
      cancer risk was shown for the combination of GSTM1 null, GSTT1 null and GSTP1
      105Val allele. The combined GSTM1 null and GSTP1 114Val allele also revealed an
      increased risk for either colon cancer (OR=4.69; 95% CI, 0.84-23.87) or rectal
      cancer (OR=5.68; 95% CI, 1.79-22.16). Furthermore, the combination of GSTM1 null,
      GSTT1 null and GSTP1 114Val allele was found in 2 rectal cancer cases.
      CONCLUSION: Our results suggest that co-exist of GSTM1 null, GSTT1 null and the
      variant GSTP1 105Val or 114Val allele may be predisposing risk factors for
      colorectal cancer in Indian population.

PMID- 20688592
TI  - Determinants of adequate follow-up of an abnormal Papanicolaou result among
      Jamaican women in Portland, Jamaica.
AB  - BACKGROUND: Among Jamaican women, cervical cancer is the second leading cause of
      cancer mortality but factors that facilitate follow-up of women receiving
      abnormal Pap smear results are not known. We examined whether socio-demographic
      factors, factors reported by the women, and assistance received for follow-up
      facilitate adequate follow-up of abnormal Pap smears. METHODS: One hundred and
      twenty-one women who had abnormal Pap results during June 1998-September 2005 in
      Portland, Jamaica were interviewed to identify determinants of adequate follow
      up. Chi-square, t-test and multivariable logistic regression analysis were used
      to identify determinants. RESULTS: Only half of the women in this sample sought
      adequate follow-up. These women had a lower number of surviving children, higher
      monthly income, and perceived the cost of services to be inexpensive. Advice
      about the timing of the follow-up activity and the next step to take by the
      healthcare workers were significant determinants of adequate follow-up. Women who
      received advice on the timing of follow-up were almost six times (adjusted OR:
      5.99, 95% CI: 1.17, 30.66, p<0.05) more likely to seek adequate follow-up after
      adjusting for other factors. CONCLUSIONS: Perceived low cost of services as well
      as assistance provided by healthcare workers regarding follow-up action helps to
      facilitate adequate follow-up of abnormal Pap smear results.

PMID- 20688593
TI  - Comparison of breast density measured by dual energy X-ray absorptiometry with
      mammographic density among adult women in Hawaii.
AB  - BACKGROUND: While use of mammography is limited, due to concerns related to
      radiation exposure, dual energy X-ray absorptiometry (DXA), commonly available in
      medical care settings, is characterized by low radiation exposure. METHODS: In
      the current paper, we compared breast density measured by DXA with mammographic
      density in 101 adult women who had a screening mammogram during the last 2 years.
      DXA scans of both breasts were taken using a clinical DXA system calibrated to
      measure breast density. The total projected breast area was manually delineated
      on each image and percent fibroglandular volume density (%FGV), absolute
      fibroglandular volume, total breast area and volume were computed. After
      digitizing mammographic films, total breast area, dense area, and percent density
      (PD) were estimated using computer-assisted mammographic density assessment.
      RESULTS: Both DXA and mammographic measures showed high correlations between left
      and right breasts ranging from 0.85 to 0.98 (p<0.0001). Mean %FGV was 38.8+/
      14.3%, and mean percent density was 31.9+/-18.2% for craniocaudal views and
      28.3+/-16.2% for mediolateral views. The correlation between the two measures was
      0.76 for both views (p<0.0001). Associations with common risk factors showed
      similar patterns for DXA and mammographic densities; in particular, the inverse
      associations with BMI and age at menarche were evident for both methods.
      Multilinear regression with stepwise selection indicated an explained variance of
      0.56 for %FGV alone and of 0.58 for %FGV plus number of children. CONCLUSION:
      Despite some differences in methodology, the current comparison suggests that DXA
      may provide a low-radiation option in evaluating breast density.

PMID- 20688594
TI  - Association between bone turnover, micronutrient intake, and blood lead levels in
      pre- and postmenopausal women, NHANES 1999-2002.
AB  - BACKGROUND: Blood lead levels (BLLs) have been shown to increase during periods
      of high bone turnover such as pregnancy and menopause. OBJECTIVES: We examined
      the associations between bone turnover and micronutrient intake with BLLs in
      women 20-85 years of age (n = 2,671) participating in the National Health and
      Nutrition Examination Survey, 1999-2002. METHODS: Serum bone-specific alkaline
      phosphatase (BAP) and urinary cross-linked N-telopeptides (NTx) were measured as
      markers of bone formation and resorption, respectively. Lead was quantified in
      whole blood. The association between tertiles of BAP and NTx, and BLLs was
      examined using linear regression with natural log transformed BLLs as the
      dependent variable and interpreted as the percent difference in geometric mean
      BLLs. RESULTS: In adjusted analyses, mean BLLs among postmenopausal women in the
      upper tertiles of NTx and BAP were 34% [95% confidence interval (CI), 23%-45%]
      and 30% (95% CI, 17%-43%) higher than BLLs among women in the lowest tertiles of
      NTx and BAP, respectively. These associations were weaker, but remained
      statistically significant, among premenopausal women (NTx: 10%; 95% CI, 0.60%
      19%; BAP: 14%; 95% CI, 6%-22%). Within tertiles of NTx and BAP, calcium intake
      above the Dietary Reference Intake (DRI), compared with below the DRI, was
      associated with lower mean BLLs among postmenopausal women but not premenopausal
      women, although most of the associations were not statistically significant. We
      observed similar associations for vitamin D supplement use. CONCLUSIONS: Bone
      resorption and bone formation were associated with a significant increase in BLLs
      among pre- and postmenopausal women.

PMID- 20688595
TI  - [Exploration of post-menopausal uterine bleeding. Hysteroscopy-histology
      correlation in 94 cases].
AB  - INTRODUCTION: Post-menopausal uterine bleeding is the reason for nearly 70% of
      gynaecological consultations. Because the cause may be a malignant disease, a
      thorough work-up is necessary to attempt to identify an organic cause. PATIENTS
      AND METHODS: This retrospective study examined 94 cases of post-menopausal
      bleeding in which both a hysteroscopic and a histological examination were
      performed in the gynaecology and obstetrics department of the Hedi Chaker
      University of Sfax from 1 January 2004 to 28 February 2005. We examined
      correlations between the hysteroscopy and histology findings as well as the
      causes determined. RESULTS: By hysteroscopy, we observed atrophic uterine linings
      in 53 patients (56%), endometrial polyps in 43 patients (45%), endometrial
      hyperplasia in 23 patients (24%) and myomas in 24 patients (25.5%). This
      examination suggested malignancy in 12 patients, among 6 of whom endometrial
      cancer was confirmed histologically. The sensitivity and specificity of
      hysteroscopy were relatively poor for the diagnosis of endometrial atrophy (about
      48.7% and 68.5%), acceptable for endometrial polyps (75% and 86.6%), endometrial
      hyperplasia (64.7% and 85.5%), and endometrial cancer (60% and 92.7%).
      CONCLUSION: Hysteroscopy is the most reliable technique for exploration, offering
      a direct view of the uterine cavity and allowing direct biopsy. Its sensitivity
      varies according to the indication and diagnosis and is sometimes very good.
      However, histology remains the reference examination for diagnosis of the cause
      of post-menopausal uterine bleeding.

PMID- 20688596
TI  - Outcomes and mechanisms of ischemic preconditioning in liver transplantation.
AB  - BACKGROUND: Liver transplantation is so far the most effective therapeutic
      modality for end-stage liver diseases, but ischemia/reperfusion (I/R) injury
      represents a critical barrier to liver transplantation. Primary graft dysfunction
      and small-for-size syndrome are closely associated with I/R injury. Ischemic
      preconditioning (IPC) is defined as a brief period of liver ischemia followed by
      reperfusion, and has demonstrated protections against a prolonged I/R injury and
      improved the capacity of regeneration. The article aimed to review IPC
      literatures for the understanding of the effects of IPC on I/R injury involving
      in the procurement of donor liver and protective mechanisms. DATA SOURCES: A
      literature search of MEDLINE and Web of Science databases using "liver
      transplantation", "liver regeneration", "hepatectomy", "ischemia/reperfusion" and
      "ischemic preconditioning" was performed, and then a large amount of related data
      was collected. RESULTS: The literature search provided a huge amount of evidence
      for the protective effects of IPC on I/R injury in liver transplantation,
      including reduction of blood loss in hepatectomy, intraoperative hemodynamic
      stability and its significant role in liver regeneration. The mechanism involves
      in balancing inflammatory cytokines, enhancing energy status and mitigating
      microcirculatory disturbance. CONCLUSION: IPC plays an essential role in
      hepatectomy before and after harvest of living donor liver and implantation of
      liver graft.

PMID- 20688597
TI  - Progress in investigating the pathogenesis of hepatopulmonary syndrome.
AB  - BACKGROUND: The pathogenesis of hepatopulmonary syndrome is complicated and
      remains unknown. This review aims to provide an updated knowledge about the
      pathogenesis of the syndrome. DATA SOURCES: Five medical databases, MEDLINE,
      ScienceDirect, OVID, Springer Link, and Wiley InterScience were searched for
      articles on "hepatopulmonary syndrome", "cirrhosis", "angiogenesis", "intestinal
      endotoxemia", "nitric oxide", "carbon monoxide", and other related subjects.
      RESULTS: Currently, imbalance between vasodilation and vasoconstriction,
      intestinal bacterial translocation, intestinal endotoxemia, and activation of the
      lung monocyte/macrophage system may play important roles in the pathogenesis of
      hepatopulmonary syndrome. Recent studies found that angiogenesis is also an
      important factor in the pathogenesis of experimental hepatopulmonary syndrome.
      CONCLUSION: Angiogenesis inhibition may be a potential approach for the treatment
      of hepatopulmonary syndrome in the future.

PMID- 20688598
TI  - Radiofrequency ablation, heat shock protein 70 and potential anti-tumor immunity
      in hepatic and pancreatic cancers: a minireview.
AB  - BACKGROUND: Radiofrequency ablation (RFA) is a minimally invasive surgical
      procedure which has widespread popularity in the treatment of hepatic and
      pancreatic cancers. Increased evidence indicates that RFA stimulates anti-tumor
      immunity, possibly through the induction heat shock protein 70 (HSP70)
      expression. HSP70 has the capacity to affect the immunogenicity of tumor cells,
      to chaperone antigenic peptides and deliver these into antigen presentation
      pathways within antigen-presenting cells, and to activate and regulate innate and
      adaptive immunity, which makes it useful in immunotherapeutic strategies for the
      treatment of cancers. DATA SOURCES: An English-language literature search was
      conducted using MEDLINE (1991-2010) on anti-tumor immunity, heat shock protein
      70, radiofrequency ablation, hepatic cancer, pancreatic cancer, and other related
      subjects. RESULTS: RFA has an increasing application in the surgical treatment of
      hepatic and pancreatic cancers. Increased evidence indicates that RFA can induce
      the expression of HSP70 which possesses properties that enable it to influence a
      variety of immunological processes. Tumor-derived HSP70 is regarded as a potent
      adjuvant facilitating presentation of tumor antigens and induction of anti-tumor
      immunity. CONCLUSIONS: This review addresses the potential association of RFA,
      HSP70, and anti-tumor immunity in treatment of hepatic and pancreatic cancers. To
      establish direct evidence of a potential association of RFA, HSP70, and anti
      tumor immunity in hepatic and pancreatic cancers, further investigations should
      be conducted.

PMID- 20688599
TI  - Outcome of hepatocellular carcinoma treated by liver transplantation: comparison
      of living donor and deceased donor transplantation.
AB  - BACKGROUND: Liver transplantation (LT) has been widely accepted as the treatment
      of choice for end-stage liver diseases. Due to the scarcity of cadaveric donors,
      adult-to-adult living donor liver transplantation (LDLT) is advocated as a
      practical alternative to deceased donor liver transplantation (DDLT). However,
      some reports suggest that the long-term and recurrence-free survival rates of
      LDLT are poorer than those of DDLT for hepatocellular carcinoma (HCC). This study
      aimed to compare the long-term and recurrence-free survival rates of HCC between
      LDLT and DDLT. METHODS: We retrospectively analyzed the clinical data of 150
      patients with HCC from January 2005 to March 2009. Eleven patients who died of
      complications during the perioperative period were excluded. The remaining 139
      eligible patients (101 DDLT and 38 LDLT) were regularly followed up to October
      2009. The Chi-square test or Fisher's exact test were used to compare the
      characteristics of LDLT and DDLT. The long-term and recurrence-free survival
      curves of both groups were determined using the Kaplan-Meier method with
      comparisons performed using the log-rank test. One-way analysis of variance was
      performed to compare the waiting time of the two groups. RESULTS: Survival rates
      at 1, 2, 3, and 4 years for LDLT were 81%, 62%, 53%, and 45% and for DDLT were
      86%, 60%, 50%, and 38%, respectively. The overall 1-, 2-, 3-, and 4-year
      recurrence-free rates for LDLT were 71%, 49%, 42%, and 38%, and for DDLT were
      76%, 52%, 41%, and 37%, respectively. No significant differences were found by
      the log-rank test on both long-term and recurrence-free survival rates.
      CONCLUSIONS: The role of LDLT is reinforced by our study. It may expand the donor
      pool and achieve the same long-term and recurrence-free survival rates of DDLT.

PMID- 20688600
TI  - Application of a medical image processing system in liver transplantation.
AB  - BACKGROUND: At present, imaging is used not only to show the form of images, but
      also to make three-dimensional (3D) reconstructions and visual simulations based
      on original data to guide clinical surgery. This study aimed to assess the use of
      a medical image-processing system in liver transplantation surgery. METHODS: The
      data of abdominal 64-slice spiral CT scan were collected from 200 healthy
      volunteers and 37 liver cancer patients in terms of hepatic arterial phase,
      portal phase, and hepatic venous phase. A 3D model of abdominal blood vessels
      including the abdominal aorta system, portal vein system, and inferior vena cava
      system was reconstructed by an abdominal image processing system to identify
      vascular variations. Then, a 3D model of the liver was reconstructed in terms of
      hepatic segmentation and liver volume was calculated. The FreeForm modeling
      system with a PHANTOM force feedback device was used to simulate the real liver
      transplantation environment, in which the total process of liver transplantation
      was completed. RESULTS: The reconstructed model of the abdominal blood vessels
      and the liver was clearly demonstrated to be three-dimensionally consistent with
      the anatomy of the liver, in which the variations of abdominal blood vessels were
      identified and liver segmentation was performed digitally. In the model, liver
      transplantation was simulated subsequently, and different modus operandi were
      selected successfully. CONCLUSION: The digitized medical image processing system
      may be valuable for liver transplantation.

PMID- 20688601
TI  - Methylprednisolone inhibits activated CD4+ T cell survival promoted by toll-like
      receptor ligands.
AB  - BACKGROUND: Methylprednisolone (MP) can affect the survival of CD4+ T lymphocytes
      and plays an important role in adaptive immune responses; however, its mechanism
      of action is not clear. Recent studies have shown that toll-like receptors (TLRs)
      on CD4+ T cells can directly modulate adaptive immune responses by affecting the
      survival and proliferation of activated CD4+ T cells. This study aimed to
      investigate the relationship between MP, TLRs and activated CD4+ T cells.
      METHODS: We separated and purified CD4+ T cells from mice, activated them in
      vitro, and co-cultured them with TLR ligands, MP or inhibitors of nuclear factor
      kappa B (NF-kappaB) and activator protein 1 (AP-1). We then assessed CD4+ T cell
      survival and proliferation and the expression of NF-kappaB and AP-1. RESULTS:
      Activated CD4+ T cells showed increased TLR-3 and TLR-9 mRNA expression, but
      polyinosinic-polycytidylic acid (poly I:C) and MP had no effect on the expression
      of these mRNAs. Still, poly I:C and CpG oligodeoxynucleotides (CpG DNA) increased
      the survival of activated CD4+ T cells, whereas MP reduced the survival of
      activated CD4+ T cells and could inhibit the survival effects of poly I:C and CpG
      DNA. The NF-kappaB essential modifier-binding domain (NBD) inhibited the survival
      of activated CD4+ T cells induced by poly I:C and CpG DNA, but the AP-1 inhibitor
      crucumin did not have the same effect. The increased expression of NF-kappaB
      induced by poly I:C and CpG DNA in activated CD4+ T cells could be inhibited by
      MP, but the same was not true for the increased expression of AP-1 induced by
      poly I:C and CpG DNA. Finally, the proliferation of activated CD4+ T cells was
      not affected by poly I:C or MP. CONCLUSION: The survival of activated CD4+ T
      cells is promoted by TLR ligands, but this effect is inhibited by MP.

PMID- 20688602
TI  - Magnetic resonance imaging-guided percutaneous cryoablation of hepatocellular
      carcinoma in special regions.
AB  - BACKGROUND: Local cryoablation guided by CT or ultrasound has been widely applied
      in the treatment of hepatocellular carcinoma. However, it is still difficult to
      apply this technique in certain regions such as the diaphragm dome, the first
      hepatic hilum, and regions adjacent to the gallbladder. This study aimed to
      evaluate the safety and efficacy of using magnetic resonance imaging (MRI)-guided
      percutaneous cryoablation as well as the effect of using an open MRI system in
      guiding and monitoring the treatment of hepatocellular carcinoma in these
      regions. METHODS: Cryoablation, guided by an open 0.35T MRI scanner and with the
      assistance of an MRI-compatible optical navigation system, was performed on 32
      patients with hepatocellular carcinoma at the diaphragm dome, the first hepatic
      hilum, and regions adjacent to the gallbladder. Each patient had one or two
      tumors. The total number of tumors treated was 36. The tumor diameters ranged
      from 2.5 to 10.0 cm (mean 4.7+/-1.8 cm). The cryosurgical system was MRI
      compatible and equipped with cryoprobes 1.47 mm in outside diameter. Under the
      guidance of MRI in combination with the optical navigation system, the cryoprobes
      were introduced percutaneously into a tumor at the planned targeting points while
      critical organs or tissues were avoided. Each cryoablation procedure included two
      freezing-thawing cycles, and MRI images were acquired dynamically to monitor the
      ablation of the tumor from time to time during the operation. In order to
      investigate the therapeutic effects of a cryoablation procedure, AFP measurements
      and liver-enhanced MRI or CT-enhanced scans were performed at regular times.
      RESULTS: MRI and optical navigation system-guided cryoablation procedures were
      successfully performed on all 32 patients (36 tumor sites) and no serious
      complications occurred. The follow-up period ranged from 5 to 12 months. The 6-
      and 12-month overall survival rates were 96.8% and 90.6%, respectively. According
      to the diagnosis of liver-enhanced MRI scans, 10 patients (31.3%) had complete
      ablation, 18 (56.3%) partial ablation (>80%), 3 (9.4%) stable disease (>50%
      ablation), and 1 (3.1%) progressive disease (a new tumor site in the liver). The
      overall efficacy was 87.5%. CONCLUSIONS: MR-guided percutaneous cryoablation
      using optical navigation is a safe and effective minimally invasive procedure for
      the treatment of hepatocellular carcinoma at certain special regions, which is
      difficult to treat with other imaging guidance approaches. With its unique and
      superb imaging functions, MRI plays an important role in the display, guidance,
      and monitoring of the cryoablation procedure in treating hepatocellular carcinoma
      at these special regions. Equipped with an MRI-compatible optical navigation
      system, MRI-guided therapy makes the cryoablation procedure more precise and
      safe.

PMID- 20688603
TI  - Efficacy of Shanvac-B recombinant DNA hepatitis B vaccine in health care workers
      of Northern India.
AB  - BACKGROUND: Health care workers (HCWs) constitute a high-risk population of HBV
      infection. There are limited data on the efficacy of vaccination in HCWs in
      India. This study was to evaluate the efficacy of indigenous recombinant
      hepatitis B vaccine, Shanvac-B, in HCWs. METHODS: In 597 HCWs screened before the
      vaccination, 216 (36.2%) showed the presence of at least one of the markers of
      HBV/HCV infection. Of the remaining 381 (63.8%) HCWs who were considered for
      vaccination, only 153 (age 18-45 years; 48 males and 105 females) were available
      for final assessment. These HCWs received 20 microg of vaccine at 0, 1 and 6
      months. They were asked for the reactogenicity and monitored for the
      seroprotective efficacy of the vaccination. Anti-HBs titres were measured after
      vaccination at 1, 2 and 7 months. The presence of anti-HBs titers equal to 1
      MIU/ml was considered as seroconversion and that of titres greater than 10 MIU/ml
      as seroprotection. RESULTS: After vaccination, 32 males (67%) and 76 females
      (72%) showed seroconvertion; finally 12 (25%) of the males and 47 (45%) of the
      females were seroprotected. Seroprotection at 2 and 7 months was more dominant in
      the females than in the males (96% vs. 56%, P=0.001, 100% vs. 85%, P=0.0001),
      respectively. Geometric mean titres of anti-HBs after vaccination were also
      higher in the females than in the males (257+/-19.7 vs. 29+/-1.88 MIU/ml, P=0.01,
      1802+/-35.2 vs. 306+/-13.6 MIU/ml, P< or =0.05, 6465+/-72 vs. 2142+/-73.6 MIU/ml,
      P<0.05). Seven male HCWs showed unsatisfactory response, non-response (n=3, 6%)
      and hypo-response (< or =10 MIU/ml, n=4, 8%) at the end of vaccination. Smoking
      and alcoholism were significantly correlated with unsatisfactory response. No
      significant adverse effects of vaccination were observed in any HCW. CONCLUSIONS:
      The presence of HBsAg in HCWs indicates that a high proportion of HCWs are
      infected with HBV and HCV in India. Recombinant indigenous vaccine Shanvac-B is
      highly efficacious in HCWs, and its immunogenicity is significantly higher in
      females than in males. However, pre-vaccination screening of HCWs is strongly
      recommended in India.

PMID- 20688604
TI  - Inflammatory bowel diseases and hepatitis C virus infection.
AB  - BACKGROUND: Data on the prevalence of hepatitis C in patients with inflammatory
      bowel diseases (IBD) are limited and conflicting. This study was to assess the
      prevalence of hepatitis C virus (HCV) infection in IBD patients and to define the
      clinical and immunologic profile of IBD associated with HCV infection. METHODS:
      Ten patients (seven females and three males) with IBD and HCV infection were
      consecutively recruited in our department between June 2005 and May 2010. We
      analyzed the clinical and serologic description of all patients. RESULTS: The
      mean age of the 10 patients was 41 years and the median disease duration was 7
      years. With present and/or past HCV infection, the patients had clinical
      manifestations and were positive for endoscopic study or histological test.
      Compared with the HCV-negative IBD group, the HCV-positive IBD group have a
      higher positive rate of autoantibodies (antinuclear antibodies, antieutrophil
      cytoplasmic antibody, and anti-SSa/SSb). In the HCV-positive group, 8 patients
      were positive for p-antieutrophil cytoplasmic antibody, 4 positive for
      antinuclear antibodies, and 3 positive for anti-SSa/SSb. Four patients had an
      elevated level of transaminase (alanine transminase, and aspartate transminase).
      CONCLUSIONS: HCV positive in IBD may induce autoanti-bodies (antinuclear
      antibodies, antieutrophil cytoplasmic antibody, anti-SSa/SSb) and damage of liver
      function. In managing IBD patients, physicians should be aware of screening of
      HCV and prescribe antiviral treatment.

PMID- 20688605
TI  - Percutaneous injection of hemostatic agents for active liver hemorrhage.
AB  - BACKGROUND: Active hemorrhage arising from hepatic injury can be life-threatening
      and require immediate attention. At present, nonoperative management of abdominal
      solid organ injuries has become the usual method of care. The purpose of this
      study was to determine whether hemocoagulase injection alone guided by contrast
      enhanced ultrasonography (CEUS) could control active bleeding in rabbit liver.
      METHODS: The livers of 30 rabbits were punctured with an 18-gauge semiautomatic
      biopsy needle to create an active bleeding liver model, which was confirmed with
      CEUS. The animals were randomly divided into two groups: a treatment group (n=15)
      and a control group (n=15). In the treatment group, hemocoagulase was injected
      into the bleeding site under CEUS guidance. In the control group, the active
      bleeding site was treated with normal saline. When these treatment procedures had
      been performed, lactated Ringer's solution was given to both groups to maintain
      the mean arterial pressure at 70 mmHg for 1 hour. The intraperitoneal blood loss,
      hematocrit, mean heart rate, and macroscopic and microscopic examinations were
      analyzed at the end of the study. RESULTS: CEUS showed hypoechoic and anechoic
      perfusion defects in active bleeding liver models. Macroscopic and microscopic
      examinations also supported the results. After the hemocoagulase injection, the
      former bleeding site appeared on CEUS as an area devoid of contrast. The blood
      loss was lower in the treatment group than in the control group (38.0+/-16.6 ml
      versus 107.9+/-20.8 ml; t=10.172, P<0.05). The mean hematocrit value and the
      heart rate were higher in the treatment group than in the control group
      (hematocrit: 23.9+/-3.8% versus 18.8+/-4.1%; t=3.541, P<0.05; heart rate: 250+/
      18 versus 223+/-15; t=4.551, P<0.01). CONCLUSION: Hemocoagulase injection alone
      under the guidance of CEUS is a simple and quick method to control blood loss in
      active liver bleeding.

PMID- 20688606
TI  - Endoscopic management of postcholecystectomy biliary leakage.
AB  - BACKGROUND: Biliary leak is an uncommon but significant complication following
      cholecystectomy. Endotherapy is an established method of treatment. However, the
      optimal intervention is not known. METHOD: Eighty-five patients with
      postcholecystectomy biliary leaks from July 2000 to March 2009 were
      retrospectively evaluated. RESULTS: The study population was 20 males and 65
      females with a mean age of 42.47 years. Patients presented with abdominal pain
      (46), jaundice (23), fever (23), abdominal distension (42), or bilious abdominal
      drain (67). Endoscopic retrograde cholangiopancreatography detected a leak at the
      cystic duct stump in 45 patients, stricture with middle common bile duct leak in
      4, leak from the right hepatic duct in 3, and a ligated common bile duct in 32.
      Twelve also had bile duct stones. One had a broken T-tube with stones.
      Endotherapy was possible in 53 patients. Three patients with stones, one with a
      broken T-tube with stones, and 4 with stricture of the common bile duct with a
      leak were managed with sphincterotomy and stenting. Eight patients with a cystic
      duct stump leak with stones were managed with sphincterotomy and stone
      extraction. Three outpatients and 12 inpatients with a cystic duct stump leak
      were managed with sphincterotomy and stent and sphincterotomy and nasobiliary
      drain, respectively. Five patients with a cystic duct stump leak were managed
      with stenting. Sixteen with coagulopathy were managed with only nasobiliary drain
      (9) or stent (7). Leak closure was achieved in 100% patients. Four developed mild
      pancreatitis which improved with conservative treatment. CONCLUSIONS: Endoscopic
      intervention is a safe and effective method of treatment of postcholecystectomy
      biliary leaks. However, management should be individualized based on factors such
      as outpatients or inpatients, presence of stone, stricture, ligature, or
      coagulopathy.

PMID- 20688607
TI  - Norcantharidin inhibits growth of human gallbladder carcinoma xenografted tumors
      in nude mice by inducing apoptosis and blocking the cell cycle in vivo.
AB  - BACKGROUND: Gallbladder carcinoma, a lethal malignant neoplasm with poor
      prognosis, has dismal results of surgical resection and chemoradiotherapy. We
      previously reported that norcantharidin (NCTD) is useful against growth,
      proliferation, and invasion of human gallbladder carcinoma GBC-SD cells in vitro.
      In this study, we further studied the inhibitory effect of NCTD on the growth of
      xenografted tumors of human gallbladder carcinoma in nude mice in vivo and the
      underlying mechanisms. METHODS: The tumor xenograft model of human gallbladder
      carcinoma in nude mice in vivo was established with subcutaneous GBC-SD cells.
      The experimental mice were randomly divided into control, 5-FU, NCTD, and NCTD+5
      FU groups which were given different treatments. Tumor growth in terms of size,
      growth curve, and inhibitory rate was evaluated. Cell cycle, apoptosis, and
      morphological changes of the xenografted tumors were assessed by flow cytometry
      and light/electron microscopy. The expression of the cell cycle-related proteins
      cyclin-D1 and p27 as well as the apoptosis-related proteins Bcl-2, Bax, and
      survivin were determined by the streptavidin-biotin complex (SABC) method and RT
      PCR. RESULTS: NCTD inhibited the growth of the xenografted tumors in a dose- and
      time-dependent manner. Tumor volume decreased (5.61+/-0.39 vs. 9.78+/-0.61 cm3,
      P=0.000) with an increased tumor inhibitory rate (42.63% vs. 0%, P=0.012) in the
      NTCD group compared with the control group. The apoptosis rate increased (15.08+/
      1.49% vs. 5.49+/-0.59%, P=0.0001) along with a decreased percentage of cells in S
      phase (43.47+/-2.83% vs. 69.85+/-1.96%, P=0.0001) in the NTCD group compared with
      the control group. The morphological changes of apoptosis such as nuclear
      shrinkage, chromatin aggregation, chromosome condensation, and typical apoptosis
      bodies in the xenografted tumor cells induced by NCTD were observed by light and
      electron microscopy. The expression of cyclin-D1, Bcl-2 and survivin
      proteins/mRNAs decreased significantly, with increased expression of p27 and Bax
      proteins/mRNAs in the NCTD group compared with the control group. CONCLUSION:
      NCTD inhibits the growth of xenografted tumors of human gallbladder carcinoma in
      nude mice by inducing apoptosis and blocking the cell cycle in vivo.

PMID- 20688608
TI  - Pancreatic duct stones in patients with chronic pancreatitis: surgical outcomes.
AB  - BACKGROUND: Pancreatic duct stone (PDS) is a common complication of chronic
      pancreatitis. Surgery is a common therapeutic option for PDS. In this study we
      assessed the surgical procedures for PDS in patients with chronic pancreatitis at
      our hospital. METHOD: Between January 2004 and September 2009, medical records
      from 35 patients diagnosed with PDS associated with chronic pancreatitis were
      retrospectively reviewed and the patients were followed up for up to 67 months.
      RESULTS: The 35 patients underwent ultrasonography, computed tomography, or both,
      with an overall accuracy rate of 85.7%. Of these patients, 31 underwent the
      modified Puestow procedure, 2 underwent the Whipple procedure, 1 underwent simple
      stone removal by duct incision, and 1 underwent pancreatic abscess drainage. Of
      the 35 patients, 28 were followed up for 4-67 months. There was no postoperative
      death before discharge or during follow-up. After the modified Puestow procedure,
      abdominal pain was reduced in patients with complete or incomplete stone
      clearance (P>0.05). Steatorrhea and diabetes mellitus developed in several
      patients during a long-term follow-up. CONCLUSIONS: Surgery, especially the
      modified Puestow procedure, is effective and safe for patients with PDS
      associated with chronic pancreatitis. Decompression of intraductal pressure
      rather than complete clearance of all stones predicts postoperative outcome.

PMID- 20688609
TI  - Endoscopic retrograde cholangiopancreatography outcome from a single referral
      center in Iran.
AB  - BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is the first
      choice for diagnostic evaluation of the pancreatic and biliary tree and can be
      accompanied by a high diagnostic sensitivity and a poor therapeutic outcome. In
      the current study, we described our experiences in the indications, findings, and
      technical success of ERCP in a sample of the Iranian population admitted to a
      referral center in Iran. METHODS: In a retrospective review database-based study,
      780 patients (393 males and 387 females; mean age 57.5 years) who had undergone
      diagnostic and therapeutic ERCP with the primary diagnosis of hepatobiliary
      disorder between 2006 and 2008 at Taleghani Hospital in Tehran were reviewed. The
      key data were demographic characteristics, clinical information, laboratory
      parameters, as well as post-ERCP complications. RESULTS: A history of
      cholecystectomy was found in about one-third (36.3%) of participants and 80
      (10.3%) out of 780 patients had a previous history of biliary stone. A minority
      (1.4%) of the patients suffered from hepatobiliary carcinomas, and 11 patients
      had cirrhosis. The most common clinical manifestations in the patients undergoing
      diagnostic ERCP were icterus (47.3%), weight loss (31.2%), and dark urine
      (26.9%). Selective biliary cannulation was technically successful in 87.0% of the
      patients; however, cannulation failed in 13.0%. The most frequent final diagnosis
      of ERCP was common bile duct stone that was detected in 40.1% of the patients.
      The ERCP results in 11.0% of the patients were normal. Regarding appropriate
      treatment, successful stenting was performed in 43 patients (15.2%). Among post
      ERCP complications, pancreatitis was the most adverse event with an incidence
      rate of 3.3%. Other complications including local bleeding, cholangitis and
      gastrointestinal perforation, rarely occurred. Post-ERCP pancreatitis was
      reported in 1.8% of men and 3.6% of women (P=0.120). Pancreatitis was more common
      in women below 70 years than in those who were older than 70 years (3.6% versus
      0.5%; OR: 8.216, P=0.015). This might be due to the more functionally active
      pancreas in younger women than in the older ones. However, other complications
      were similar in the two age groups. CONCLUSIONS: Based on our experience, ERCP
      indications, final diagnosis and related complications are comparatively
      consistent with those reported in other countries. The most common post-ERCP
      complication is pancreatitis that is more often observed in younger patients.

PMID- 20688610
TI  - Giant cell tumor of the pancreas: a pathological diagnosis with poor prognosis.
AB  - BACKGROUND: Giant cell tumors are rare and highly malignant tumors of the
      pancreas. Based on two distinct cell populations, they have been divided into two
      subtypes corresponding to the osteoclast-like giant cell tumor and the
      pleomorphic giant cell carcinoma of the pancreas. Distinctive imaging features of
      the tumors remain uncharacterized. Surgical removal is the only appropriate
      treatment for them, but responses to chemotherapy or radiotherapy remain
      undocumented. METHODS: Clinical, radiological, histopathologic, and
      immunohistochemical features of two cases of giant cell tumor of the pancreas are
      presented along with a brief review of the literature. RESULTS: En-bloc resection
      was done successfully in both cases. The patient with an osteoclast-like giant
      cell tumor remained disease-free with no clinical or radiological evidence of
      recurrence at 6 months after surgery. However, the patient with the pleomorphic
      type died 4 months later due to diffuse pulmonary metastasis. CONCLUSIONS: En
      bloc surgical resection is the only appropriate treatment for giant cell tumors.
      The overall prognosis of these tumors is poorer than that of pancreatic ductal
      adenocarcinoma, especially the pleomorphic type. More studies are required to
      document the management and outcomes of the tumors.

PMID- 20688611
TI  - Total laparoscopic hysterectomy after liver transplantation.
AB  - BACKGROUND: The number of females who undergo liver transplantation is growing
      and sometimes gynecologic operations are needed to control gynecologic diseases
      after liver transplantation. METHOD: Total laparoscopic hysterectomy was
      performed in 2 patients who had undergone liver transplantation, one for
      adenomyosis and the other for hysteromyoma. RESULTS: It was safe to create a
      pneumoperitoneum through the umbilical skinfold even though mild adhesion in the
      pelvic cavity occurred in one patient. The operative times were 95 and 90
      minutes, with blood loss of about 100 and 60 ml, respectively. Oral intake,
      flatus passage, and ambulation recovered within a day, after the operation. No
      significant changes in liver function were observed except complication of
      diarrhea caused by Candida albicans in one patient. CONCLUSIONS: The result of
      the two patients suggest that total laparoscopic hysterectomy is a safe and
      effective surgical approach for patients who have undergone liver
      transplantation.

PMID- 20688612
TI  - Primary pancreatic hydatid disease associated with acute pancreatitis.

PMID- 20688613
TI  - Sitagliptin in treatment of diabetes complicated by chronic hepatitis C.

PMID- 20688614
TI  - Liver injury associated with Malva grandifolia.

PMID- 20688615
TI  - Risk factors for cerebral palsy in term birth infants.
AB  - PURPOSE: The aim of this study was to identify the antenatal, intrapartum and
      neonatal risk factors in term birth infants for cerebral palsy (CP) among babies
      in a hospital-based study. MATERIALS AND METHODS: The medical records of children
      with cerebral palsy referred to our Pediatric Rehabilitation Department in
      Bialystok were reviewed. Antenatal, intrapartum, and neonatal events were
      compared among 213 children with CP and 280 controls in a retrospective study. We
      studied live births >36 weeks gestation born between January 1, 1990, and
      December 31, 2005. RESULTS: Fifty-seven percent of the infants with CP were male.
      Spastic tetraplegia 78 (36.61%) and spastic hemiplegia 65 (30.51%) were the
      dominant types of CP. Factors associated with an increased risk of CP identified
      as antenatal and intrapartum risk factors were pre-eclampsia, abruptio placenta,
      and placenta previa. Birth asphyxia occurred significantly more often (p<0.001)
      in children with CP compared to controls. In the neonatal period, respiratory
      distress syndrome, meningitis and neonatal seizures were associated with an
      increased incidence of CP. CONCLUSION: Our findings confirm that several
      antenatal, intrapartum and neonatal risk factors for CP in term birth infants
      contribute to the etiology of CP.

PMID- 20688616
TI  - The retrospective evaluation of pneumonia and bronchitis cases in infants and
      small children with atopic dermatitis in the practice of a family doctor -
      personal observations.
AB  - PURPOSE: The purpose of the work is to estimate the occurrence of lower
      respiratory tract infections in infants and small children with atopic dermatitis
      and to compare them with a group of children at the same age without features of
      allergy. MATERIAL AND METHODS: The study has been conducted on the basis of the
      retrospective analysis of medical documentation of individual history of disease
      among children born in 2005 - 2008 treated in an outpatient clinic. RESULTS:
      Children suffering from atopic dermatitis are more prone to pneumonia and
      bronchitis. They are also more often hospitalized due to these reasons. Also,
      this group of patients is more liable to wheezing in the time of infection.
      CONCLUSIONS: Infants and small children with atopic dermatitis are more prone to
      lower respiratory tract infections. Recurrence of infections within the
      respiratory system may be an important risk factor for asthma.

PMID- 20688618
TI  - Impact of environmental endocrine disrupting chemicals on the development of
      obesity.
AB  - Environmental chemicals with hormone-like activity can disrupt programming of
      endocrine signaling pathways during development and result in adverse effects,
      some of which may not be apparent until much later in life. Recent reports link
      exposure to environmental endocrine disrupting chemicals during development with
      adverse health consequences, including obesity and diabetes. These particular
      diseases are quickly becoming significant public health problems and are fast
      reaching epidemic proportions worldwide. This review summarizes data from
      experimental animals and humans which support an association of endocrine
      disrupting chemicals, such as diethylstilbestrol, bisphenol A, phytoestrogens,
      phthalates, and organotins, with the development of obesity. Potential mechanisms
      are summarized and future research needs are discussed.

PMID- 20688617
TI  - Physiological effects and mechanisms of action of endocrine disrupting chemicals
      that alter estrogen signaling.

PMID- 20688619
TI  - Sex determination and disorders of sex development according to the revised
      nomenclature and classification in 46,XX individuals.
AB  - There have been considerable advances concerning understanding of the early and
      later stages of ovarian development; a number of genes have been implicated and
      their mutations have been associated with developmental abnormalities. The most
      important genes controlling the initial phase of gonadal development, identical
      in females and males, are Wilms' tumor suppressor 1 (WT1) and steroidogenic
      factor 1 (SF1). Four genes are likely to be involved in the subsequent stages of
      ovarian development (WNT4, DAX1, FOXL2 and RSPO1), but none is yet proven to be
      the ovarian determining factor. Changes in nomenclature and classification were
      recently proposed in order to incorporate genetic advances and substitute gender
      based diagnostic labels in terminology. The term "disorders of sex development"
      (DSD) is proposed to substitute the previous term "intersex disorders". Three
      main categories have been used to describe DSD in the 46,XX individual: 1)
      disorders of gonadal (ovarian) development: ovotesticular DSD, previously named
      true hermaphroditism, testicular DSD, previously named XX males, and gonadal
      dysgenesis; 2) disorders related to androgen excess (congenital adrenal
      hyperplasia, aromatase deficiency and P450 oxidoreductase deficiency); and 3)
      other rare disorders. In this mini-review, recent advances concerning development
      of the genital system in 46,XX individuals and related abnormalities are
      discussed. Basic embryology of the ovary and molecular pathways determining
      ovarian development are reviewed, focusing on mutations disrupting normal ovarian
      development. Disorders of sex development according to the revised nomenclature
      and classification in 46,XX individuals are summarized, including genetic
      progress in the field.

PMID- 20688620
TI  - The differential impact of volatile and intravenous anaesthetics in humans.

PMID- 20688621
TI  - Neuroendocrine dysfunction in patients recovering from subarachnoid hemorrhage.
AB  - OBJECTIVE: Subarachnoid hemorrhage (SAH) is a recently identified risk factor for
      hypopituitarism, particularly growth hormone (GH) and corticotrophins
      deficiencies. The aim of our study was to identify possible predictor(s) for
      neuroendocrine dysfunction in SAH survivors. DESIGN: Pituitary function was
      evaluated in 93 patients (30 males, 63 females), aged 48.0+/-1.1 years (mean+/
      SE), and with a Glasgow Outcome Scale score of 4.6+/-0.6 (mean+/-SE) more than
      one year following SAH. In the acute phase, SAH was complicated by vasospasm (VS)
      in 18 and by hydrocephalus (HDC) in 9 patients. Baseline serum values of insulin
      growth factor 1 (IGF-I), cortisol, thyroxine (T4), thyroid stimulating hormone
      (TSH), follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone
      (in males), estradiol (in females) and prolactin were determined. RESULTS:
      According to the results of baseline hormonal evaluation, 47 patients (50.5%) had
      no hormonal abnormalities. Seven patients (7.5%) had multiple pituitary hormone
      deficiencies: Four patients (4.3%) had two (GH and cortisol), one patient had
      three (gonadal, adrenal and GH) and two patients had deficiency of all pituitary
      axes. Thirty-nine patients (42%) had one abnormal axis (13 adrenal, 2 thyroid, 4
      gonadal and 20 GH). None of the subjects was treated with desmopressin or
      exhibited symptomatic polyuria. The VS and HDC during the acute phase of SAH were
      related to abnormal pituitary status (VS with low IGF-I levels and HDC with low
      cortisol levels). CONCLUSION: Through a screening procedure, neuroendocrine
      dysfunction was identified in a substantial number of asymptomatic patients with
      previous SAH. Cerebral VS and HDC at the time of SAH emerged as risk factors
      possibly predicting development of pituitary dysfunction. Low basal levels of IGF
      1 and cortisol may help in selecting patients requiring further evaluation of
      pituitary function.

PMID- 20688622
TI  - Combined therapy with L-thyroxine and L-triiodothyronine compared to L-thyroxine
      alone in the treatment of primary hypothyroidism.
AB  - OBJECTIVE: The objective of this study was to compare various parameters in
      patients with hypothyroidism receiving either monotherapy with L-thyroxine (L-T4)
      or combination therapy with L-T4 and L-triiodothyronine (L-T3). DESIGN: We
      conducted a randomized, controlled trial in 36 premenopausal women with
      hypothyroidism. The patients were divided into two groups: Group A (n=20)
      received only L-T4, while Group B received the combination L-T4 and L-T3. The
      treatment period lasted for 6 months. RESULTS: At baseline, the various
      parameters examined did not differ in the two groups. No significant difference
      between monotherapy and combined therapy was demonstrated on TSH level, ECG
      monitoring, densitometry, or thyroid symptoms score. The lipid profile was better
      during combined treatment compared to L-T4 alone; in Group A during treatment
      with L-T4 the levels of cholesterol and low density lipoprotein (LDL) cholesterol
      were unchanged, while in group B total cholesterol and LDL decreased (p<0.05).
      The changes in osteocalcin levels did not differ in the two groups, whereas the
      levels of urine deoxypyridinoline at the end of therapy were higher in the group
      with combination therapy, compared to monotherapy. CONCLUSION: Compared with L-T4
      alone, replacement therapy with the combination of L-T4+L-T3 shows favourable
      changes in serum lipid profile, but higher activation of bone resorption.

PMID- 20688623
TI  - High rates of obesity prevalence in adults living in central Greece: data from
      the ARGOS study.
AB  - OBJECTIVE: To investigate the prevalence of obesity in adults of a large region
      of Central Greece. DESIGN: The target group was adults aged 18 to 79 years who
      were residents of the region of Thessaly for at least one year. A sample of 852
      individuals stratified for sex and age were included. Each subject underwent a
      thorough physical examination and body mass index (BMI) was calculated from body
      weight and height. Waist and hip circumferences as well as body fat content were
      additionally measured. RESULTS: Mean (SD) BMI for the total population was 27.5+/
      5.5 and was significantly higher in males than in females (28.2+/-4.4 vs. 26.9+/
      6.2, p<0.001). The overall prevalence of obesity was 26.6% distributed equally
      between men (27.8%) and women (25.6%), whereas prevalence of overweight was 39.4%
      with male predominance (50.8% vs. 29.3%, p<0.001). Morbid obesity (MO) was found
      in 3.5% with female predominance. The prevalence of central obesity, using waist
      circumference cut-off points (>102cm for men, >88cm for women), was comparable in
      males (40.4%) and females (35.3%). There was a positive association between
      obesity, central obesity, and age. The prevalence of overweight (19.5%) and
      obesity (9.4%) in the age-range of 18-29 years almost doubled in the next decade
      of age and attained the highest value, respectively, in the age-range of 50 to 59
      (48.2%), and of 60 to 70 years group (38.9%). CONCLUSIONS: The rates of
      overweight and obesity in the population of Thessaly are relatively high with
      overweight being more prominent in males than in females, whereas MO was higher
      in females compared to males.

PMID- 20688624
TI  - Relationship between serum zinc levels, thyroid hormones and thyroid volume
      following successful iodine supplementation.
AB  - OBJECTIVE: Zinc is essential for many biochemical processes and also for cell
      proliferation. Thyroid hormones influence zinc metabolism by affecting zinc
      absorption and excretion. Additionally, zinc deficiency affects thyroid function.
      The aim of the present study was to evaluate a possible association of zinc
      levels with thyroid volume, thyroid hormones and thyroid autoantibody levels in
      healthy subjects, patients with autoimmune thyroid disease (AITD) and patients
      with nodular goitre following successful iodine supplementation. This is a cross
      sectional study in which 201 subjects who were not under medical treatment and
      did not have previous thyroid surgery or radio-iodine treatment were evaluated.
      Seventy patients had nodular goitre, 67 AITD and 64 had normal thyroid. Thyroid
      volume was calculated by ultrasonographic measurements. Serum free T4, T3, TSH,
      anti-thyroglobulin and anti-thyroid peroxidase levels were determined by
      appropriate methodology. RESULTS: In patients with normal thyroid, zinc levels
      were significantly positively correlated with free T3 levels (p<0.001). In the
      nodular goitre group, thyroid volume was negatively correlated with TSH and
      circulating zinc levels (p=0.014 and p=0.045, respectively). In the AITD group,
      thyroid autoantibodies and zinc were significantly positively correlated.
      Multiple regression analysis revealed a significant relationship between thyroid
      volume and zinc only in the patients with nodular goitre (p=0.043). CONCLUSION:
      There was significant correlation of serum zinc levels with thyroid volume in
      nodular goitre patients, with thyroid autoantibodies in AITD and with free T3 in
      patients with normal thyroid.

PMID- 20688625
TI  - Optic neuropathy following radiotherapy for Cushing's disease: case report and
      literature review.
AB  - Radiation-induced optic neuropathy is a rare adverse effect of radiotherapy
      applied for the treatment of pituitary adenomas. We report a patient with a
      recurrent adrenocorticotrophin secreting pituitary adenoma who received external
      beam irradiation after failing surgical and medical therapy. Sixteen months after
      radiotherapy, the patient was presented with declining visual acuity, and
      radiation-induced optic neuropathy was diagnosed. Despite treatment with
      glucocorticoids and hyperbaric oxygen, her vision did not improve. The
      pathophysiology, prevention and treatment of radiation-induced optic neuropathy,
      including the efficacy of hyperbaric oxygen therapy are reviewed.

PMID- 20688626
TI  - Cinacalcet in hyperparathyroidism secondary to X-linked hypophosphatemic rickets:
      case report and brief literature review.
AB  - X-linked dominant hypophosphatemic rickets (XLH) is the most prevalent genetic
      form of hypophosphatemic rickets. Standard treatment of XLH patients includes
      long-term administration of phosphate and calcitriol. Treated patients usually
      respond well to the conventional therapy and demonstrate amelioration of rachitic
      symptoms and improved growth. However, long-term administration of phosphate and
      vitamin D preparations is sometimes complicated with nephrocalcinosis, secondary
      or tertiary hyperparathyroidism and arterial hypertension. We describe a patient
      with XLH, caused by a rare missense mutation of the PHEX gene. The patient, while
      under treatment with alphacalcidol and oral phosphate, developed hypercalciuria,
      nephrocalcinosis, secondary hyperparathyroidism and arterial hypertension.
      Cinacalcet was added to the therapeutic regimen and the long-term effects on
      calciotropic parameters and FGF23 levels are herein reported.

PMID- 20688627
TI  - Pathogen dynamics and morbidity of striped skunks in the absence of rabies.
AB  - Parasites have the potential to influence the population dynamics of mammalian
      hosts, either as a single devastating pathogen or as a community effect. Striped
      skunks (Mephitis mephitis) are typically host to rabies, which often regulates
      population numbers. We assessed micro- and macroparasite dynamics in striped
      skunk populations in the absence of rabies, to determine if a single pathogen, or
      community, was responsible for a majority of skunk deaths. We monitored mortality
      due to pathogens, and prevalence of pathogens via serology and necropsy, in two
      populations of striped skunks in northern Illinois during 1998-2004.
      Transmissible pathogens requiring direct transmission (i.e., canine distemper
      virus, canine parvovirus) exhibited high annual variability in prevalence. In
      contrast, those pathogens employing a more indirect, environmental route of
      transmission (i.e., Leptospira interrogans and Toxoplasma gondii) appeared to
      exhibit relatively less annual variability in prevalence. Skunks were diagnosed
      with infections from an average of 4.08 (SD=2.52, n=32) species of endoparasites,
      with a range of 1-11. Macroparasite prevalence and intensity did not vary among
      seasons, or sex or age of host. Severe infections occurred with multiple parasite
      species, and patterns of aggregation suggested some parasite species, or more
      likely the parasite community, act as a limiting mechanism in skunk populations.

PMID- 20688628
TI  - Neospora caninum and Toxoplasma gondii antibody prevalence in Alaska wildlife.
AB  - Free-ranging caribou and moose populations in some regions of Alaska undergo
      periodic declines in numbers. Caribou and moose are managed by the state as
      valuable resources for not only sustenance and subsistence, but also for cultural
      heritage. Incidence and prevalence of diseases that may impact herd health and
      recruitment from year to year are relevant to management decisions aimed to
      protect the long-term viability of these herds. Neospora caninum and Toxoplasma
      gondii are two apicomplexan parasites that can cause neurologic disease and
      abortions in their intermediate hosts and less frequently cause disease in their
      definitive hosts. The definitive hosts of N. caninum and T. gondii are canids and
      felids, respectively, and prevalence in the environment is in part dependent on
      maintenance of the life cycle through the definitive hosts. Serum samples from
      caribou (Rangifer tarandus, n=453), wolf (Canis lupus, n=324), moose (Alces
      alces, n=201), black-tailed deer (Odocoileus hemionus, n=55), coyote (Canis
      latrans, n=12), and fox (Vulpes vulpes, n=9) collected in Alaska were assayed for
      N. caninum- and T. gondii-reactive antibodies with an immunofluorescent antibody
      test (IFAT) and a modified agglutination test (MAT), respectively. Seroprevalence
      of N. caninum was greater in caribou (11.5%) than in wolves (9.0%), moose (0.5%),
      or black-tailed deer (0%). Seroprevalence of T. gondii was greater in wolves
      (17.8%) than in caribou (0.4%), moose (0%), or black-tailed deer (0%).
      Seroprevalence of N. caninum and T. gondii were 16.7% and 0.0% in coyotes and
      0.0% and 12.5% in fox, but small sample sizes prevented further analysis.
      Antibodies to N. caninum in young caribou compared to adult caribou suggest that
      vertical transmission may be an important component of new infections in Alaskan
      caribou. The spatial distribution of antibody-positive individuals across Alaska
      may reflect differences in frequency of definitive hosts and alteration of
      predation patterns among regions.

PMID- 20688629
TI  - Flea abundance, diversity, and plague in Gunnison's prairie dogs (Cynomys
      gunnisoni) and their burrows in montane grasslands in northern New Mexico.
AB  - Plague, a flea-transmitted infectious disease caused by the bacterium Yersinia
      pestis, is a primary threat to the persistence of prairie dog populations
      (Cynomys spp.). We conducted a 3-yr survey (2004-2006) of fleas from Gunnison's
      prairie dogs (Cynomys gunnisoni) and their burrows in montane grasslands in
      Valles Caldera National Preserve in New Mexico. Our objectives were to describe
      flea communities and identify flea and rodent species important to the
      maintenance of plague. We live-trapped prairie dogs and conducted burrow sweeps
      at three colonies in spring and summer of each year. One hundred thirty prairie
      dogs and 51 golden-mantled ground squirrels (Spermophilus lateralis) were
      captured over 3,640 trap nights and 320 burrows were swabbed for fleas. Five flea
      species were identified from prairie dogs and ground squirrels and four were
      identified from burrow samples. Oropsylla hirsuta was the most abundant species
      found on prairie dogs and in burrows. Oropsylla idahoensis was most common on
      ground squirrels. Two colonies experienced plague epizootics in fall 2004. Plague
      positive fleas were recovered from burrows (O. hirsuta and Oropsylla tuberculata
      tuberculata) and a prairie dog (O. hirsuta) in spring 2005 and summer 2006. Three
      prairie dogs collected in summer 2005 and 2006 had plague antibody. We found a
      significant surge in flea abundance and prevalence, particularly within burrows,
      following plague exposure. We noted an increased tendency for flea exchange
      opportunities in the spring before O. hirsuta reached its peak population. We
      hypothesize that the role of burrows as a site of flea exchange, particularly
      between prairie dogs and ground squirrels, may be as important as summer
      conditions that lead to buildup in O. hirsuta populations for determining plague
      outbreaks.

PMID- 20688630
TI  - Epizootiologic survey of Mycobacterium bovis in wildlife and farm environments in
      northern Michigan.
AB  - Bovine tuberculosis (bovine TB), caused by Mycobacterium bovis, has reemerged in
      northern Michigan, USA, with detections in white-tailed deer (Odocoileus
      virginianus) in 1994 and in cattle in 1998. Since then, significant efforts have
      been directed toward reducing deer densities in the area in the hopes of reducing
      the bovine TB prevalence rate in deer and eliminating spillover of the disease
      into cattle. Despite the success of the efforts to reduce deer densities,
      additional cattle herds have become infected. Other mammals can be infected with
      M. bovis, and some carnivores and omnivores had been found to be infected with
      the disease in northern Michigan, USA. We conducted a multiyear surveillance
      effort to detect bovine TB in wild species of mammals in the Michigan, USA,
      outbreak area. From 2002 to 2004, tissue samples from 1,031 individual animals of
      32 species were collected, processed, and cultured for M. bovis. Only 10 (1.0%)
      were culture-positive for M. bovis (five raccoons [Procyon lotor], four opossums
      [Didelphis virginiana], and one grey fox [Urocyon cinereoargenteus]). We also
      found two raccoons and four opossums to be positive for Mycobacterium avium. We
      collected 503 environmental samples from cattle farms recently identified as
      bovine TB positive; none yielded positive M. bovis culture results. Finally, we
      used infrared cameras to document wildlife use of four barns in the area. Many
      avian and mammalian species of wildlife were observed, with raccoons being the
      most commonly observed species. This surveillance study identified no new
      wildlife species that should be considered significant reservoirs of bovine TB in
      the outbreak area in northern Michigan, USA. However, the relatively high,
      apparent bovine TB prevalence rates in some carnivorous and omnivorous species,
      their relatively long life spans, and their frequent use of barns, suggests that
      removal of raccoons, opossums, foxes, and coyotes (Canis latrans) should be
      considered when a newly infected farm is depopulated of cattle.

PMID- 20688631
TI  - Salmonella enterica subsp. Enterica in Cattle Egret (Bubulcus ibis) chicks from
      central Texas: prevalence, serotypes, pathogenicity, and epizootic potential.
AB  - Cattle Egrets have a worldwide distribution, feed in proximity to cattle and
      other domestic animals, and often nest in large colonies in urban woodlots. Over
      a 3-yr period, nestlings from five Cattle Egret colonies from Central Texas, USA,
      were surveyed for salmonellosis. Prevalence of infection ranged from 29% to 95%.
      Seventeen Salmonella enterica subsp. enterica serotypes were isolated, of which
      the 4,5,12:i-monophasic serotype predominated in cultures of both the digestive
      tract and pooled spleen and liver. Of 11 4,5,12:i-monophasic isolates phage
      typed, eight were determinate type 193. The 4,5,12:i-monophasic isolates were
      susceptible to all antibiotics tested and were highly invasive in the day-old
      chick infection model. Microscopic lesions were found in the livers of Cattle
      Egrets with systemic infections with the 4,5,12:i-monophasic serotype, suggesting
      that infections with this serotype may often be fatal. Twenty-nine serotypes were
      identified in 179 S. enterica subsp. enterica isolates from horses admitted to
      the Texas A&M University Veterinary Teaching Hospital in 2 yr following the
      Cattle Egret study. The 4,5,12:i-monophasic serotype was not isolated from
      horses, but 12 serotypes were isolated from both horses and Cattle Egrets. The
      temporal distribution of the horse cases suggested that Cattle Egrets and horses
      may be exposed to similar sources of Salmonella, but provided no evidence of
      transmission between these two species. Similar conclusions were drawn when
      Cattle Egret isolates were compared to isolates from feedlot and dairy cattle
      from Texas and surrounding states. Given that the Cattle Egret 4,5,12:i
      monophasic serotype was highly invasive and other isolates of this serotype have
      been associated with food poisoning, it is likely that Cattle Egret colonies pose
      a health risk to humans living near them.

PMID- 20688632
TI  - Hematology and blood chemistry reference values and age-related changes in wild
      Bearded Vultures (Gypaetus barbatus).
AB  - Normal hematologic and blood chemistry values for clinical use and age-related
      changes are reported as reference values for the endangered Bearded Vulture
      (Gypaetus barbatus). Blood samples were obtained from 21 nestlings and 26 free
      living subadults and adults. No significant differences were found between
      subadults and adults or between sexes for any of the studied parameters.
      Reference ranges have been established for Bearded Vulture nestlings (less than 3
      mo of age) and for free-living Bearded Vultures, with subadult and adult data
      combined without affecting clinical interpretation. Some reference values for the
      parameters reported in this study are similar to those previously described for
      vultures and other raptor species, although creatine phosphokinase and lactate
      dehydrogenase activities were higher than those reported for birds of prey.
      Significant age-related differences were identified in urea, uric acid,
      triglycerides, total serum protein, inorganic phosphorus, and magnesium
      concentrations, as well as aspartate aminotransferase, creatine phosphokinase,
      lactate dehydrogenase, alkaline phosphatase, amylase, and lipase activities
      (P<0.05). Additionally, significant age-related differences were noted in red and
      white blood cell counts, packed cell volume, hemoglobin concentration, mean
      corpuscular volume, mean corpuscular hemoglobin concentration, fibrinogen level,
      and heterophils, lymphocytes, and eosinophils (P<0.005). The results obtained
      from this study provide reference ranges that will be useful for evaluating the
      pathologic conditions and general health of Bearded Vulture populations and
      reveal the existence of important age-related differences in the species.

PMID- 20688633
TI  - Pathology associated with West Nile virus infections in the yellow-billed magpie
      (Pica nuttalli): a California endemic bird.
AB  - Yellow-billed Magpies (Pica nuttalli, Corvidae) are found exclusively in central
      California and have experienced alarming West Nile virus (WNV)-associated
      mortality since 2004. The first reported case of WNV in the species was reported
      in July 2004. Subsequently, 81% (304/374) of dead magpies submitted that year to
      the California Department of Health Services Dead Bird Surveillance Program were
      WNV positive by polymerase chain reaction (PCR) test. We studied 43 magpie
      carcasses collected in 2004 and observed distinctive lesions in 24 birds that
      tested positive for WNV. Lesions included vasculitis and necrosis, and organs
      affected included brain, heart, liver, and gastrointestinal tract. From the
      severity of lesions observed, we suspect that a rapid onset of morbidity and
      mortality occurs with the Yellow-billed Magpie. Examination of bird survey data
      indicates that Yellow-billed Magpie abundance declined coincidentally with the
      onset of WNV in California. The home range and habitat of the species are nested
      within known areas of WNV transmission. Yellow-billed Magpies may be at risk of a
      decline and population bottleneck. Observations and experience with the Yellow
      billed Magpie and WNV may provide insights for other endangered corvids that have
      not yet been exposed to WNV, including the Hawaiian Crow (Corvus hawaiiensis) and
      Island Scrub Jay (Aphelocoma insularis).

PMID- 20688634
TI  - Bronchoalveolar lavage and pulmonary histopathology in harp seals (Phoca
      groenlandica) experimentally infected with Otostrongylus circumlitus.
AB  - The objective of this study was to characterize pathologic changes associated
      with experimental infection of harp seals (Phoca groenlandica) with the lungworm
      Otostrongylus circumlitus (Metastrongyloidea: Crenosomatidae). The leukocyte
      differential cell count in samples obtained by unguided bronchoalveolar lavage
      (BAL) and the intensity of the histologic lesions in the lungs were assessed in
      seven harp seals experimentally exposed to 300 infective, third-stage O.
      circumlitus larvae. Seven unexposed harp seals were used as controls. First-stage
      larvae were observed in the feces of three of the seven exposed seals at 38, 42,
      and 45 days postexposure (dpe). Adult nematodes were found in the right primary
      bronchi of two of these three seals at necropsy 53 dpe. Fifty-six BALs were
      performed on the 14 seals. No statistical difference was observed between the
      exposed and control seals and among the four sampling times in percentage of
      neutrophils and macrophages in the BAL fluid. A significant difference was
      observed between the exposed and control seal groups in the percentage of
      eosinophils (P<0.0001), the count of eosinophils having increased by a factor of
      70.4 in exposed seals. Significant statistical differences were observed between
      exposed and control seals in intensity of interstitial inflammation (P=0.001),
      bronchitis (P=0.02), bronchiolitis (P=0.04), alveolitis (P=0.03), and
      interstitial granulomatous inflammation (P=0.04). Our findings showed that harp
      seals are susceptible to infection with O. circumlitus. However, parasitic
      infections were transient and of low intensity, at least under our experimental
      conditions.

PMID- 20688635
TI  - Pathology and distribution of sea turtles landed as bycatch in the Hawaii-based
      North Pacific pelagic longline fishery.
AB  - We examined the gross and microscopic pathology and distribution of sea turtles
      that were landed as bycatch from the Hawaii, USA-based pelagic longline fishery
      and known to be forced submerged. Olive ridley turtles (Lepidochelys olivacea)
      composed the majority of animals examined, and hook-induced perforation of the
      esophagus was the most common gross lesion followed by perforation of oral
      structures (tongue, canthus) and of flippers. Gross pathology in the lungs
      suggestive of drowning was seen in 23 of 71 turtles. Considering only the
      external gross findings, the pathologist and the observer on board the longline
      vessel agreed on hook-induced lesions only 60% of the time thereby illustrating
      the limitations of depending on external examination alone to implicate hooking
      interactions or drowning as potential cause of sea turtle mortality. When
      comparing histology of drowned turtles to a control group of nondrowned turtles,
      the former had significantly more pulmonary edema, hemorrhage, and sloughed
      columnar epithelium. These microscopic changes may prove useful to diagnose
      suspected drowning in sea turtles where history of hooking or netting
      interactions is unknown.

PMID- 20688636
TI  - Natural history of Sin Nombre virus infection in deer mice in urban parks in
      Oregon.
AB  - Sin Nombre virus (SNV), one of at least 45 hantaviruses described worldwide, is
      hosted by the deer mouse, Peromyscus maniculatus, a common species throughout
      most of North America. Herein, we describe general life-history characteristics
      of deer mice and the ways in which these factors relate to the incidence of SNV
      infections among populations of this host species in and around Portland, Oregon.
      In total, 3,175 deer mice were captured from October 2002 to September 2005.
      Transmission of SNV appears to be associated with male breeding behaviors, as
      more males and adults were infected than expected by capture rate; spring and
      summer had the highest infection prevalence, as well as scrotal male captures.
      Wounding rates between infected and uninfected deer mice were not different in
      any age or sex class. Capture rates were significantly and positively related to
      the interaction of temperature departure from normal, total precipitation, and
      number of clear days from two seasons previous (P=0.029), while infection
      prevalence was significantly and negatively related to the capture rate of
      juveniles from two seasons previous (P=0.029).

PMID- 20688637
TI  - Status of brucellosis in free-ranging elk and bison in Wyoming.
AB  - Brucella abortus is the causative agent of brucellosis, a disease enzootic in
      populations of free-ranging elk (Cervus elaphus) and bison (Bison bison) in the
      Greater Yellowstone Ecosystem, USA. We define the distribution of the disease in
      elk throughout Wyoming, USA, using three epidemiologic/geographic classifications
      based on winter-foraging opportunity. Antibody prevalence for >3,300 yearling and
      adult, female elk, sampled from supplemental feedgrounds in western Wyoming, USA,
      since 1985, was 21.9%. Surveillance of nearly 3,800 winter free-ranging, adult,
      female elk, sampled from herd units adjacent to feedgrounds from 1991 to 2008,
      indicated a total antibody prevalence of 3.7%. In contrast, none of the 1,930
      male and female elk sampled from 1991 to 2008 in herd units distant from
      feedgrounds in Wyoming, USA, demonstrated exposure to B. abortus. In comparison
      to elk, bison had a higher incidence of brucellosis. Surveillance of 321 cow
      bison harvested within the Absaroka and Jackson bison herds in western Wyoming,
      USA, from 1992 to 2008 yielded an antibody prevalence of 63.9%.

PMID- 20688638
TI  - Causes of mortality in northern fur seals (Callorhinus ursinus), St. Paul Island,
      Pribilof Islands, Alaska, 1986-2006.
AB  - To determine whether infectious diseases might have contributed to the present
      day decline of northern fur seals (Callorhinus ursinus), preweaned pups
      (n=2,735), subadult males (n=98), and adults (n=179) were examined postmortem
      from 1986 to 2006 on St. Paul Island, Alaska. Gross necropsy findings and
      histologic lesions were used to determine causes of death. Five general
      categories of mortality were identified for pups: emaciation (1,454 pups, 53%),
      trauma (497 pups, 18%), perinatal mortality (516 pups, 19%), infectious diseases
      (82 pups, 3%), and miscellaneous causes (186 pups, 7%). A condition of unknown
      etiology characterized by multifocal necrotizing myopathy and cardiomyopathy was
      found in 92 pups. Thirty-three congenital anomalies were identified in 49 pups,
      including a rare multicentric ganglioneuroblastoma. General linear models were
      used to examine change in pup mortality and condition (i.e., pup mass) over time.
      The prevalence of perinatal mortality appeared to increase during the study and
      relative to past reports. Trauma and infectious conditions appeared to decrease
      slightly from 1986 to 2006. Although relatively stable during this investigation,
      emaciation was greater than that reported for past studies. Emaciated pups
      weighed less than expected during 1988, 1996, and 2004 and more than expected
      during 1987, 1989, 1990, and 1994 (P</=0.003). Average annual weights for all
      other categories of mortality did not change significantly from 1986 to 2006.
      Fatal conditions for subadult males included hyperthermia, blunt trauma,
      entanglement, and bite wounds; nonfatal conditions included seizures, orange
      discoloration of the blubber, neoplasia, and parasitism. Causes of mortality for
      most adults included bite wounds with cellulitis and secondary infections,
      pulmonary edema, dystocia, blunt trauma, and neoplasia. We found no evidence to
      implicate infectious diseases as a cause in the recent decline of northern fur
      seals.

PMID- 20688639
TI  - Serosurvey for canine distemper virus, canine adenovirus, Leptospira interrogans,
      and Toxoplasma gondii in free-ranging canids in Scandinavia and Svalbard.
AB  - Prevalence of antibodies reactive to canine distemper virus (CDV), canine
      adenovirus type 1 (CAV-1), Leptospira interrogans serovars Canicola and
      Icterohaemorrhagiae, and Toxoplasma gondii were examined in free-ranging
      Scandinavian canids. Sampling included 275 red foxes (Vulpes vulpes) from
      mainland Norway, 60 arctic foxes (Vulpes lagopus) from the high-arctic islands of
      Svalbard, and 98 wolves (Canis lupus) from the joint Swedish-Norwegian
      population. Methods used included virus neutralization tests for CDV and CAV-1, a
      microscopic agglutination test for L. interrogans, and a direct agglutination
      test for T. gondii. High prevalence of antibody to CAV-1 was identified in red
      foxes (59.6%), wolves (67.7%), and arctic foxes (37.8%). The prevalence of
      antibody to CDV varied between 9.6% and 12.3% in the three species. Antibodies to
      L. interrogans serovar Icterohaemorrhagiae were found in 9.9% of the red foxes
      and 8.4% of the wolves sampled, whereas no antibody-positive arctic foxes were
      found. All animals were antibody-negative for L. interrogans serovar Canicola.
      Antibodies to T. gondii were found in 66.9, 51.7, and 18.6% of red foxes, arctic
      foxes and wolves, respectively. Significantly more adults than juveniles were
      antibody-positive for CDV in red foxes and arctic foxes, for CAV-1 in wolves, and
      for T. gondii in red foxes and wolves. There was a general tendency for adult
      female red foxes to have a higher prevalence of antibodies for CDV than adult
      males; this difference was statistically significant. The results indicate that
      CDV and CAV-1 are endemic in red foxes and wolves on the Scandinavian mainland
      and in arctic foxes on Svalbard. Although infection with L. interrogans serovar
      Icterohaemorrhagiae was relatively common in wild canids on mainland Norway, it
      was not found on Svalbard, where the maintenance host (Rattus norvegicus) is
      absent. All three species are commonly exposed to T. gondii through predation on
      infected intermediate hosts.

PMID- 20688640
TI  - Avian paramyxoviruses in shorebirds and gulls.
AB  - There are nine serotypes of avian paramyxovirus (APMV), including APMV-1, or
      Newcastle disease virus. Although free-flying ducks and geese have been
      extensively monitored for APMV, limited information is available for species in
      the order Charadriiformes. From 2000 to 2005 we tested cloacal swabs from 9,128
      shorebirds and gulls (33 species, five families) captured in 10 states within the
      USA and in three countries in the Caribbean and South America. Avian
      paramyxoviruses were isolated from 60 (0.7%) samples by inoculation of
      embryonating chicken eggs; isolates only included APMV-1 and APMV-2. Two isolates
      (APMV-2) were made from gulls and 58 isolates (APMV-1 [41 isolates] and APMV-2
      [17 isolates]) were made from shorebirds. All of the positive shorebirds were
      sampled at Delaware Bay (Delaware and New Jersey) and 45 (78%) of these isolates
      came from Ruddy Turnstones (Arenaria interpres). The APMV-1 infection rate was
      higher among Ruddy Turnstones compared with other shorebird species and varied by
      year. Avian paramyxovirus-2 was isolated from two of 394 (0.5%) Ruddy Turnstones
      at Delaware Bay in 2001 and from 13 of 735 (1.8%) Ruddy Turnstones during 2002.
      For both APMV-1 and APMV-2, infection rates were higher among Ruddy Turnstones
      sampled on the south shore of Delaware Bay compared to north shore populations.
      This spatial variation may be related to local movements of Ruddy Turnstones
      within this ecosystem. The higher prevalence of APMV in Ruddy Turnstones mirrors
      results observed for avian influenza viruses in shorebirds and may suggest
      similar modes of transmission.

PMID- 20688641
TI  - Eighteen-year study of South Australian dolphins shows variation in lung
      nematodes by season, year, age class, and location.
AB  - Between 1990 and 2007, carcasses of opportunistically collected short-beaked
      common dolphins (Delphinus delphis; n=238), Indo-Pacific bottlenose dolphins
      (Tursiops aduncus; n=167), and common bottlenose dolphins (Tursiops truncatus;
      n=15) were examined for parasites and life history data. Three species of lung
      nematodes (Halocercus lagenorhynchi, Stenurus ovatus, Pharurus alatus) were
      identified in surface nodules, subsurface lesions, or airways. Nematode burdens
      were light to heavy and, in many cases, would have compromised the dolphins'
      health. The number of dolphins infected was related to species, year, season, age
      class, and geographic region. Nematodes were found in all three species but were
      more prevalent in short-beaked common dolphins (mean annual prevalence=26%) than
      in bottlenose dolphins (12%). There was a significant increase in prevalence of
      nematodes in short-beaked common dolphins in 2005-06 (63%) compared to 1990-2004
      (14%), with a peak in April-June. More young short-beaked common dolphins were
      infected than subadults and adults and, during the unusual infection event, there
      were more dependent calves (<130 cm) than juveniles. There were also more
      infections in dependent bottlenose dolphin (Tursiops spp.) calves but no increase
      in overall prevalence was detected during 2005-06. Because neonates of both short
      beaked common dolphins and bottlenose dolphins were infected, mother-to-calf
      transmission is suspected for these species in South Australia. Numbers of
      infections in short-beaked common dolphins were higher in Gulf St Vincent than
      elsewhere in South Australia, particularly in 2005-06. The cause of the unusual
      infection event in short-beaked common dolphins is unknown. We discuss the
      influence of dolphin diet, life history, and external factors.

PMID- 20688642
TI  - Avian botulism: a case study in translocated endangered Laysan Ducks (Anas
      laysanensis) on Midway Atoll.
AB  - Laysan Ducks are endemic to the Hawaiian archipelago and are one of the world's
      most endangered waterfowl. For 150 yr, Laysan Ducks were restricted to an
      estimated 4 km(2) of land on Laysan Island in the northwestern Hawaiian Islands.
      In 2004 and 2005, 42 Laysan Ducks were translocated to Midway Atoll, and the
      population increased to approximately 200 by 2007. In August 2008, mortality due
      to botulism type C was identified, and 181 adult, fledgling, and duckling
      carcasses were collected from August to October. Diseased birds were found on two
      islands within Midway Atoll at multiple wetlands; however, one wetland
      contributed most carcasses. The epidemic was discovered approximately 14-21 days
      after the mortality started and lasted for 50 additional days. The details of
      this epidemic highlight the disease risk to birds restricted to small island
      populations and the challenges associated with managing newly translocated
      endangered species. Frequent population monitoring for early disease detection
      and comprehensive wetland monitoring and management will be needed to manage
      avian botulism in endangered Laysan Ducks. Vaccination may also be beneficial to
      reduce mortality in this small, geographically closed population.

PMID- 20688643
TI  - Relationships between local carcass density and risk of mortality in molting
      mallards during avian botulism outbreaks.
AB  - Removal of bird carcasses has been advocated for management of Clostridium
      botulinum outbreaks on lakes in North America because a reduction in density of
      toxin-laden maggots produced within bird carcasses is assumed to enhance survival
      of healthy birds. This inverse relationship between carcass density and survival
      has been reported in controlled studies with Mallards (Anas platyrhynchos) but
      has not been verified in wild ducks during naturally occurring botulism
      outbreaks. Therefore, we radio-marked 204 molting Mallards on seven lakes in
      western Canada during July-August 1999-2000, and monitored their survival daily
      for 30 days. Carcass searches were conducted simultaneously at 90 matched
      locations for freshly dead and randomly selected live radio-marked Mallards.
      Carcass density (carcasses/ha) averaged about two times greater at dead than at
      live duck locations (x = 12.4, SE= 1.2 vs. x= 5.0, SE= 0.7). Predicted risk of
      mortality increased rapidly with carcass density (case-control logistic
      regression: model-averaged beta(density)= 0.167, unconditional SE= 0.062).
      Mallards exposed to 5-11 and >11 carcasses/ ha were 3.5 and 13 times more likely
      to die, respectively, than were Mallards inhabiting carcass-free areas. Mortality
      risk was more closely related to density of maggot-laden carcasses than to maggot
      free carcass densities. Our results are consistent with the assumption that
      reducing carcass density could enhance survival. However, we caution that
      survival rates may remain low on lakes in which areas with high carcass densities
      persist due to incomplete carcass removal.

PMID- 20688644
TI  - Effects of serotonin agonists and doxapram on respiratory depression and
      hypoxemia in etorphine-immobilized impala (Aepyceros melampus).
AB  - Respiratory depression is a common side effect when opioids are used to
      immobilize wildlife. Serotonergic ligands have the potential to reverse opioid
      induced respiratory depression. We examined whether any of three serotonergic
      ligands could reverse this depression in etorphine-immobilized (0.07 mg/kg)
      impala (Aepyceros melampus). The study took place in September-December 2007.
      Impala received intravenous injections of metoclopramide (10 mg/kg, n=6),
      buspirone (0.05 mg/kg, n=8), pimozide (1 mg/kg, n=8), doxapram (1 mg/kg, n=6),
      and control solutions on separate occasions. During the immobilization, partial
      pressures of oxygen (PaO(2), mmHg) and carbon dioxide (PaCO(2), mmHg),
      respiratory rate (breaths/min), ventilation (l/min), peripheral O(2) saturation
      (%), tidal volume (l), and respiratory exchange ratio were measured before and
      after injection of the experimental drugs. Etorphine immobilization caused
      respiratory depression and hypoxia (mean+/-SD, PaCO(2)=51+/-2 mmHg, PaO(2)=40+/-3
      mmHg). Metoclopramide and buspirone, but not pimozide, attenuated the hypoxic
      effects of etorphine; 3 min after injection, metoclopramide increased the PaO(2)
      by 7.5+/-6.3 mmHg and buspirone by 6+/-6.6 mmHg (F=3.9, P=0.02). These effects
      were similar to those of doxapram (8+/-7 mmHg, F=3.9; P>0.05). Neither
      metoclopramide nor buspirone significantly increased ventilation, but they
      increased PaO(2) by significantly improving the alveolar-arterial oxygen partial
      pressure gradient (A-a gradient, F=1.4, P<0.05), indicating improved oxygen
      diffusion. Metoclopramide and buspirone transiently improved blood oxygenation of
      opioid-immobilized impala, probably by improving ventilation-perfusion ratios,
      without reversing catatonic immobilization.

PMID- 20688645
TI  - Hepatic mineral values of white-tailed deer (Odocoileus virginianus) from
      Virginia.
AB  - There is a lack of information on mineral requirements of free-ranging white
      tailed deer (Odocoileus virginianus). In addition, mineral deficiencies or
      excesses may play a role in the development of parasitism/malnutrition syndrome.
      We measured hepatic mineral values in apparently healthy white-tailed deer from
      two sites in Virginia, USA, as well as in deer with presumptive
      parasitism/malnutrition syndrome during 2005-2007. Deer with presumptive
      parasitism/malnutrition syndrome that were displaying signs of emaciation and
      chronic diarrhea had significantly higher mean hepatic levels of magnesium (Mg)
      and zinc (Zn) compared with healthy deer. Healthy deer in our study from northern
      Virginia, USA (i.e., Fairfax, Fauquier, Loudoun, and Prince William counties) had
      significantly lower mean hepatic selenium (Se) levels compared with deer from
      Nottoway County, Virginia, USA, which is 200 km distant. Healthy deer from
      northern Virginia, USA, also had significantly lower mean hepatic cobalt (Co),
      copper (Cu), and molybdenum (Mo) levels. Adult deer had significantly higher mean
      levels of hepatic iron (Fe) compared with fawns. In addition, male deer had
      significantly higher mean hepatic Co levels compared with female deer. The
      significantly higher mean (+/-SD) level of Zn in sick deer from northern
      Virginia, USA (78.7+/-54.9 microg/g versus 35.8+/-7.4 microg/g in healthy deer)
      is potentially clinically significant, although no signs consistent with Zn
      poisoning were observed. All deer in our study from northern Virginia, USA, had
      marginal or deficient levels of Cu (mean+/-SD=27.4+/-18.3 microg/g) and Se
      (mean=0.08+/-0.03 microg/g), which may be predisposing this population to the
      development of parasitism/malnutrition syndrome.

PMID- 20688646
TI  - Evidence of lead exposure in a free-ranging population of Kea (Nestor notabilis).
AB  - Kea (Nestor notabilis) are high country parrots endemic to New Zealand. The
      foraging behavior and inquisitive nature of Kea have led to incidences of foreign
      substance ingestion, including lead. Between April 2006 and November 2007, 38 Kea
      in Aoraki/Mount Cook National Park, New Zealand, were captured, and blood was
      sampled for blood lead analysis. All birds sampled had detectable blood lead with
      concentrations ranging from 0.028 mg/l to 3.43 mg/l (mean+/-SE, 0.428+/-0.581
      mg/l). A retrospective analysis of necropsy reports and archived samples from 15
      wild Kea from various South Island locations also was carried out. Seven of these
      birds (five from the Aoraki/Mount Cook area) died with clinical signs consistent
      with lead toxicosis and had liver and/or kidney lead levels reported to cause
      lead toxicity in other avian species. All seven of these birds also had lead
      inclusions (Ziehl-Neelson positive intranuclear inclusion bodies) in the renal
      tubular epithelial cells. These are considered diagnostic of lead toxicity in
      other species. This study showed that lead exposure is ubiquitous in the sampled
      population and may be an important contributing factor in Kea morbidity and
      mortality. As a result of these findings, lead abatement in areas frequented by
      Kea is being initiated.

PMID- 20688647
TI  - Immunomodulatory effects upon in vitro exposure of California sea lion and
      southern sea otter peripheral blood leukocytes to domoic acid.
AB  - During red tide bloom events, the marine diatom Pseudo-nitzschia produces the
      toxin domoic acid (DA), which has been associated with stranding and mortality
      events involving California sea lions (Zalophus californianus) and southern sea
      otters (Enhydra lutris). In addition to these well-documented DA-induced
      neurotoxic events, there is increasing concern that DA may exert chronic effects,
      such as immunomodulation, which may potentially increase an individual's
      susceptibility to a number of opportunistic infections following nonlethal
      exposure. We investigated the effects of DA on innate (phagocytosis and
      respiratory burst) and adaptive (mitogen-induced lymphocyte proliferation) immune
      functions with the use of peripheral blood leukocytes collected from healthy
      California sea lions and southern sea otters upon in vitro exposure to 0
      (unexposed control), 0.0001, 0.001, 0.01, 0.1, 1.0, 10, and 100 microM DA. Domoic
      acid did not significantly modulate phagocytosis or respiratory burst in either
      species. For California sea lions, DA significantly increased ConA-induced T
      lymphocyte proliferation upon exposure to DA concentrations ranging from 0.0001
      to 10 microM, resulting in a nonlinear dose-response curve. There was no effect
      on lymphocyte proliferation at the highest concentration of DA tested. No effects
      on lymphocyte proliferation were observed in southern sea otters. Importantly,
      the in vitro DA concentrations affecting T-cell proliferation were within or
      below the range of DA in serum measured in free-ranging California sea lions
      following natural exposure, suggesting a risk for immunomodulation in free
      ranging animals. Understanding the risk for immunomodulation upon DA exposure
      will contribute in the health assessment and management of California sea lions
      and southern sea otters, as well as guide veterinarians and wildlife
      rehabilitators in caring for and treating afflicted animals.

PMID- 20688648
TI  - Prevalence of Actinobacillus pleuropneumoniae infection in hunted wild boars (Sus
      scrofa) in Germany.
AB  - Actinobacillus pleuropneumoniae is an important pathogen of the porcine
      respiratory tract. Subclinically and chronically infected pigs may enter a
      permanent carrier state, harboring A. pleuropneumoniae in lungs or tonsils.
      Despite the enormous role of A. pleuropneumoniae in domestic swine production, no
      published data about prevalence and distribution of A. pleuropneumoniae
      infections in wild boars (Sus scrofa) are available. Antibodies against A.
      pleuropneumoniae have been detected in serum of wild boars from Slovenia. The aim
      of the present study was to evaluate A. pleuropneumoniae infection status in wild
      boars in Germany. Tissue samples from lungs and tonsils of 531 wild boars from 52
      hunts during the hunting seasons 2004-05 to 2006-07 were examined for A.
      pleuropneumoniae by polymerase chain reaction (PCR). Although gross pathologic
      lesions typical for pleuropneumonia were not detected, 35.8% of the wild boars
      were PCR-positive. Tonsils were involved in 94.3% and lungs in 15.5%.
      Actinobacillus pleuropneumoniae infection prevalence increased with age and body
      weight. Further research is needed to understand the involvement of different A.
      pleuropneumoniae serotypes and to understand the interrelationship of A.
      pleuropneumoniae infection between wild boars and domestic pigs.

PMID- 20688649
TI  - A dermal melanoma in a young common seal (Phoca vitulina).
AB  - A subcutaneous melanocytic tumor was diagnosed during the rehabilitation period
      of a stranded 7-mo-old common seal (Phoca vitulina) suffering from parasitic
      bronchopneumonia. The clinical signs of the seal as well as the histopathology of
      the tumor are described. This is the first time a melanocytic tumor has been
      diagnosed in a common seal. The mass was identified as a low-grade dermal
      melanoma.

PMID- 20688650
TI  - Studies of "unsteady gait disease" of the Tibetan gazelle (Procapra
      picticaudata).
AB  - Clinical signs of a disease locally referred to as "unsteady gait disease" for
      the Tibetan gazelle (Procapra picticaudata) were observed in the Qinghai Lake
      watershed area, China. The objective of this study was to determine if there was
      a relationship between the disease and copper (Cu) deficiency. Chemical
      examinations showed that Cu concentrations in soil and forage samples were
      similar from areas where gazelles were affected and unaffected. However,
      concentrations of sulfur (S) and molybdenum (Mo) in the soil and forage samples
      from the affected area were significantly higher than those from the unaffected
      areas (P<0.01). Copper concentrations in samples of blood, hair, and liver from
      the affected gazelles were significantly lower than those in unaffected animals
      (P<0.01). Supplementation of CuSO(4) in affected gazelles improved their appetite
      and vigor. We conclude that the disorder of Tibetan gazelles was caused by Cu
      deficiency, attributable to the high S and Mo content in forage.

PMID- 20688651
TI  - Serologic-based investigation of leptospirosis in a population of free-ranging
      eastern grey kangaroos (Macropus giganteus) indicating the presence of Leptospira
      weilii serovar Topaz.
AB  - Eastern grey kangaroos (Macropus giganteus) are one of the most abundant large
      macropodids sharing the landscape with humans. Despite this, little is known
      about the prevalence of Leptospira carriage within this species and the role that
      they may partake in the transmission of this disease in Australia. The sera of 87
      free-ranging eastern grey kangaroos, captured in the Warragamba Catchment Area,
      Sydney, Australia, from June 2004 to November 2006, were screened against a
      reference panel of 22 Leptospira serovars using the microscopic agglutination
      test (MAT). Leptospiral antibodies were detected in 47% (41 of 87) of serum
      samples collected. Leptospira weilii Topaz, a newly emergent serovar in
      Australia, was detected in all seropositive kangaroos (41 of 41; 100%). The sex
      and tail-fat body condition index of kangaroos appeared to have no significant
      effect on the exposure to the disease. This serologic-based study is the first
      reported for L. weilii serovar Topaz in New South Wales, to our knowledge, having
      previously been isolated only in humans and two other animal species (bovine and
      long-nosed bandicoot [Perameles nasuta]) in Western Australia and Queensland. The
      potential role of eastern grey kangaroos in the maintenance and zoonotic spread
      of the disease to livestock and humans is discussed.

PMID- 20688652
TI  - First report of Acanthocheilonema spirocauda in the Mediterranean monk seal
      (Monachus monachus).
AB  - The Mediterranean monk seal (Monachus monachus) is one of the world's most
      endangered marine mammals. The largest population is located mainly throughout
      the Aegean and Ionian islands and along the coastline of southern continental
      Greece. We report the findings of a necropsy and discuss their potential
      importance to the conservation of the species. The adult female monk seal
      appeared to be in a good nutritional state. The main necropsy findings were
      injuries consistent with a violent and sudden death, including three round wounds
      on the ventral surface of the body and several hematomas, as well as a
      decomposing male fetus in the uterus. Two nematodes were found in the right
      ventricle of the heart; no abnormalities were observed in the lungs, pulmonary
      vessels, or heart. The nematodes were identified as Acanthocheilonema spirocauda.
      This is the first report of infection of the Mediterranean monk seal with A.
      spirocauda, even though this is the most common heartworm found in most pinnipeds
      worldwide. This parasite should be considered in health care monitoring projects
      of this endangered species.

PMID- 20688653
TI  - No evidence of blood parasites in Little Auks (Alle alle) breeding on Svalbard.
AB  - Absence of blood parasites in birds occurring in polar regions is believed to be
      a common phenomenon but only few surveys have been conducted on truly polar bird
      species. We examined blood parasites in a seabird with an exclusively high-Arctic
      breeding distribution, the Little Auk (Alle alle). Polymerase chain reaction was
      used to detect haemosporidians and traditional optical microscopy was used to
      detect a wider range of haematozoans in birds breeding on Svalbard (Norway). No
      blood parasites were found among 100 birds examined. This finding confirms
      scarcity of haematozoa in polar regions and provides baseline data for the Little
      Auk.

PMID- 20688654
TI  - Scoliosis in a tiger salamander (Ambystoma tigrinum) associated with encysted
      digenetic trematodes of the genus Clinostomum.
AB  - A group of 202 tiger salamanders (Ambystoma tigrinum) was brought into captivity
      due to habitat destruction. Half of these animals died, over two mo, showing
      generalized hemorrhages compatible with an infectious disease, but an etiologic
      agent was not determined. Encysted metacercarial stages of trematodes within the
      skeletal musculature, coelomic cavity, and subcutaneous space were additional
      necropsy findings. One salamander had scoliosis and multiple skin nodules. A
      radiograph showed no skeletal abnormality to explain the scoliosis; however,
      numerous round nodules were more radiodense than the surrounding tissue. A
      presumptive diagnosis of generalized trematodiasis was made, yet the salamander
      did not improve after a course of praziquantel and subsequently died. Necropsy
      revealed massive, encysted trematode infection. Histologic examination revealed
      marked multifocal intramuscular, subcutaneous, and coelomic trematodiasis with
      associated necrosis and inflammation. Based on gross morphology, the trematode
      was identified as a member of the genus Clinostomum.

PMID- 20688655
TI  - New records of hair follicle mites (Demodecidae) from North American Cervidae.
AB  - Individuals of three species of cervids, with varying degrees of alopecia, were
      examined for ectoparasites: Rocky Mountain elk (Cervus elaphus nelsoni) and mule
      deer (Odocoileus hemionus hemionus) in Colorado and white-tailed deer (Odocoileus
      virginianus) in South Dakota. Hair follicle mites were recovered and identified
      as Demodex kutzeri, a species originally described from the European red deer
      (Cervus elaphus, from Austria) and the sika deer (Cervus nippon pseudaxis,
      captive in Germany). These findings expand the geographic range of D. kutzeri to
      North America and extend its host range to include the genus Odocoileus. Thus,
      the host range for D. kutzeri spans two subfamilies of cervids. Additionally, D.
      kutzeri was identified in material from a white-tailed deer collected in South
      Carolina in 1971, indicating this parasite has been present, but unrecognized, on
      US cervids for some time.

PMID- 20688656
TI  - Blood chemistry of wild Brazilian Coscoroba Swans during molt.
AB  - The Coscoroba Swan (Coscoroba coscoroba) is an unusual member of the Anatidae
      found in South America, from the Falkland Islands and Tierra del Fuego through
      Chile and Argentina, Uruguay, and Paraguay as far north as Mato Grosso do Sul in
      Brazil. The species is not threatened globally, but some local populations have
      declined and the status of others is unknown. The objective of this study was to
      quantify the plasma chemistry of a wild population of Coscoroba Swans in southern
      Brazil during their molting period. We captured 12 chicks, 14 juveniles, and 31
      mature birds. The following blood parameters were measured: glucose, cholesterol,
      triglycerides, HDL cholesterol, uric acid, creatine-kinase, aspartate amino
      transferase, alanine-aminotransferase, alkaline phosphatase, amylase, and
      pancreatic amylase. Significant differences between males and females were not
      observed for any of the parameters, and only the levels of alkaline phosphatase
      differed significantly among age groups.

PMID- 20688657
TI  - Experimental xylazine-ketamine anesthesia in the common carp (Cyprinus carpio).
AB  - The potential anesthetic effect of ketamine in combination with xylazine was
      examined in the common carp (Cyprinus carpio). Anesthesia (indicated by cessation
      of voluntary swimming and loss of responses to pinching the skin with forceps and
      pricking the tail with a needle) was induced by mixing 14.4 ml of ketamine (5%
      solution), or 11.4 ml of xylazine (2% solution), or both, in 10 l of water
      containing 10 fish/group. Xylazine alone induced sedation and anesthesia in 5
      12.3 min with a mean duration of 7.3 min. Ketamine alone induced similar effects
      in 7.2-9.7 min for an average of 24.2 min. Combined xylazine and ketamine took
      longer (14-22.8 min) to induce sedation and anesthesia, but the duration was
      longer (42.7 min). The respiratory rates of anesthetized fish significantly
      decreased in all treatments when compared to controls. In conclusion, the
      combination of xylazine-ketamine was found to induce smooth anesthesia in the
      common carp for a time sufficient for common clinical and surgical interventions.

PMID- 20688658
TI  - Helminths of Sotalia guianensis (Cetacea: Delphinidae) from the south and
      southeastern coasts of Brazil.
AB  - From May 1997 to October 2000, 49 Sotalia guianensis (tucuxi dolphin)
      incidentally caught in fishing nets or stranded in Sao Paulo (SP) and Parana (PR)
      states in Brazil were necropsied. In total, 17 lungs, 35 stomachs, and 30
      intestines were analyzed. Contents were washed through a sieve (mesh, 150 mm) and
      examined under a stereoscopic microscope for parasites. Histopathologic analyses
      were performed in the lungs of five infected dolphins. The nematode Halocercus
      brasiliensis was found in 88% of all lungs examined, inducing moderate-to-severe
      pneumonia. Braunina cordiformis, Anisakis sp., and acanthocephalans were found in
      the stomachs. The trematode Synthesium tursionis was the only parasite found in
      the intestines, and it was identified in 73% of the animals necropsied. No
      macroscopic lesions were seen due to parasites in the stomachs and intestines
      analyzed.

PMID- 20688659
TI  - Prevalence of West Nile virus in wild American Kestrels (Falco sparverius) of
      southern Quebec, Canada.
AB  - We assessed West Nile virus (WNV) antibody prevalence in American Kestrels (Falco
      sparverius) in southern Quebec by sampling 152 birds during the 2003-05 breeding
      seasons. We analyzed the dependence of antibody prevalence on age group, year,
      and gender; a significant relationship was detected only between age (adults vs.
      nestlings) and antibody prevalence. Furthermore, reproductive success did not
      appear to be linked with the prevalence of anti-WNV antibodies in this
      population.

PMID- 20688660
TI  - Antibodies to pathogenic livestock viruses in a wild vicuna (Vicugna vicugna)
      population in the Argentinean Andean altiplano.
AB  - Serum samples from 128 wild vicunas (Vicugna vicugna) were tested for antibodies
      (Ab) to rotavirus (RV), bovine parainfluenza virus 3 (BPIV-3), bovine herpesvirus
      1 (BHV-1), bovine viral diarrhea virus (BVDV-1), foot-and-mouth disease virus
      (FMDV), bluetongue virus (BTV), equine herpesvirus-1 (EHV-1), and influenza A
      virus equine (EIV). Samples were collected in Cieneguillas Province of Jujuy, in
      northern Argentina. Feces from 44 vicunas were also collected to investigate RV
      shedding. Llamas (Lama glama) and domestic cattle (Bos taurus) from the area
      studied also were tested for antibodies to these viruses. Antibodies against RV
      (100%) and BPIV-3 (37%) were detected in the vicunas sampled. No RV antigen was
      detected in any of the fecal samples tested. One vicuna was positive for Ab to
      BHV-1 (0.8%) and another for BVDV-1 (0.8%). The Ab prevalences detected in llamas
      were: 100% (16/16) for RV, 47% (8/17) for BPIV-3, 17.6% (3/17) for BHV-1, and
      5.9% (1/17) for BVDV-1. However, domestic cattle had high antibody prevalences
      for RV and BPIV-3, 100% (13/13) and 73% (11/15), respectively, but were negative
      for Ab to BHV-1 and BVDV. No antibodies against FMDV, BTV, EHV-1, or EIV were
      detected in wild vicunas or domestic species. Because no data of viral
      circulation on wild vicunas are available, this report represents the first
      evidence of viral infection in wild vicunas from the Argentinean Andean Puna.

PMID- 20688661
TI  - Babesia (Theileria) annae in a red fox (Vulpes vulpes) from Prince Edward Island,
      Canada.
AB  - A 4-6-mo-old female red fox (Vulpes vulpes) was presented to the Atlantic
      Veterinary College (AVC) Teaching Hospital, Prince Edward Island, Canada. On
      presentation, the fox was weak and had pale mucous membranes. A complete blood
      count and a serum biochemistry profile were performed. Blood smear examination
      revealed low numbers of erythrocytes containing centrally to paracentrally
      located, single, rarely multiple, approximately 1 x 2 microm, oval to round
      organisms with morphology similar to Babesia microti. Polymerase chain reaction
      testing and DNA sequencing of the Babesia species 18S rRNA gene were performed on
      DNA extracted from whole blood. Results were positive for a Babesia microti-like
      parasite genetically identical to Babesia (Theileria) annae. The fox was
      euthanized due to poor prognosis for recovery. Necropsy examination revealed
      multifocal to locally extensive subacute nonsuppurative meningoencephalitis, an
      eosinophilic broncho-pneumonia, a moderate diffuse vacuolar hepatopathy, and
      lesions associated with blunt trauma to the left abdominal region. This is the
      first reported case of a red fox in Canada infected with a piroplasm. It remains
      uncertain whether the presence of this hemoparasite in this fox was pathogenic or
      an incidental finding. The potential for competent vectors of Babesia species on
      Prince Edward Island, the potential for this Babesia microti-like parasite to
      infect other wild and domestic canids, and the significance of this parasite to
      the health of infected individuals are yet to be determined.

PMID- 20688662
TI  - Detection of Helicobacter in the digestive tract of an Atlantic spotted dolphin
      (Stenella frontalis).
AB  - Helicobacter spp. occur in the digestive system of a broad range of animal taxa,
      including marine mammals. Only one formally recognized species, Helicobacter
      cetorum, has been described in marine mammals. Helicobacter has not been reported
      in the Atlantic spotted dolphin (Stenella frontalis). The purpose of our study
      was to examine the digestive tract of a stranded spotted dolphin for
      Helicobacter. Tissue and content samples were collected at necropsy and examined
      by histopathology and molecular analyses using Helicobacter genus-specific 16S
      rDNA polymerase chain reaction (PCR) and DNA sequencing. Helicobacter was
      detected in all stomach divisions and the duodenal ampulla. A sequence type of
      the 16S rRNA gene shared a 98-99% identity to sequences from H. cetorum. This
      study reports for the first time Helicobacter in S. frontalis.

PMID- 20688663
TI  - Bovine tuberculosis in livestock and wild boar on the Mediterranean island,
      Corsica.
AB  - The zoonotic agent of bovine tuberculosis (bTB), Mycobacterium bovis, can be
      transmitted between domestic and wild animals, threatening wildlife populations
      and control programs for bTB in cattle. In Corsica, a French Mediterranean island
      where domestic and wild species have close interactions, bTB cases have been
      reported in cattle, pigs, and wild boar. Moreover, genotypes of M. bovis found in
      wild and domestic animals from the same area were identical. These data strongly
      suggest that wild and domestic animals are associated in an epidemiologic bTB
      transmission cycle. More investigations are needed, not only to understand the
      role played by each species in order to implement appropriate control measures,
      but also to assess the risk of transmission to humans.

PMID- 20688664
TI  - Asymptomatic Babesia microti-like parasite infection in wild raccoon dogs
      (Nyctereutes procyonoides) in South Korea.
AB  - We describe asymptomatic piroplasmosis caused by a Babesia microti-like parasite
      in wild raccoon dogs (Nyctereutes procyonoides) diagnosed by blood smear and DNA
      analysis. This is the first description of natural B. microti-like parasite
      infection in raccoon dogs and suggests that the wild raccoon dog can be a source
      for B. microti-like parasite infection of domestic dogs and humans.

PMID- 20688665
TI  - Detection of Yersinia pestis DNA in prairie dog-associated fleas by polymerase
      chain reaction assay of purified DNA.
AB  - We evaluated, refined, and applied well-established polymerase chain reaction
      (PCR) techniques for detecting Yersinia pestis DNA in fleas (mainly Oropsylla
      spp.) collected from prairie dog (Cynomys spp.) burrows. Based on results from
      PCR of avirulent Y. pestis strain A1122 DNA, we used DNA purification and primers
      for the plasminogen activator gene to screen field-collected fleas. We detected
      Y. pestis DNA in flea pools from two black-tailed prairie dog (Cynomys
      ludovicianus) colonies with evidence of recent plague epizootics, and from one of
      four white-tailed prairie dog (Cynomys leucurus) colony complexes (Wolf Creek)
      where evidence of epizootic plague was lacking. Relative flea abundance and
      occurrence of Y. pestis DNA among flea pools appeared to vary over time at Wolf
      Creek. Both DNA purification and primer sequences appeared to influence the
      likelihood of detecting Y. pestis DNA by PCR in fleas collected from prairie dog
      burrows in the absence of observed epizootic plague. Presence of Y. pestis
      plasmid DNA in fleas collected from prairie dog burrows at Wolf Creek may
      represent evidence that infected fleas were somehow being maintained in that
      system between epizootics, consistent with the hypothesized enzootic maintenance
      of plague in prairie dog colony complexes elsewhere.

PMID- 20688666
TI  - Hematologic and plasma biochemistry values for endangered red knots (Calidris
      canutus rufa) at wintering and migratory sites in Argentina.
AB  - We obtained hematologic and plasma biochemistry values for adult, long-distance
      migrant Red Knots at their southernmost wintering site in Rio Grande (Tierra del
      Fuego, Argentina) and at the first stopover site in San Antonio Oeste (Rio Negro,
      Argentina). Lymphocytes (L) followed by heterophils (H) were the most abundant
      leukocytes. H/L ratio and glucose levels were significantly higher at Rio Grande,
      possibly because of the stress of migration and molting. Packed cell volume
      results ranged widely, probably in response to increased oxygen demand for
      migration. Protein profiles and lipids were higher at the stopover site and
      attributable to birds storing reserves for subsequent flights.

PMID- 20688667
TI  - DNA barcoding techniques for avian influenza virus surveillance in migratory bird
      habitats.
AB  - Avian influenza virus (AIV) circulates among free-ranging, wild birds. We
      optimized and validated a DNA barcoding technique for AIV isolation and host
      species identification using fecal samples from wild birds. DNA barcoding was
      optimized using tissue and fecal samples from known bird species, and the method
      was shown to distinguish 26 bird species. Subsequently, fecal samples (n=743)
      collected from wild waterfowl habitats confirmed the findings from the laboratory
      tests. All identified AIV-positive hosts (n=35) were members of the order
      Anseriformes. We successfully applied the DNA barcoding technique to AIV
      surveillance and examined AIV epidemiology and host ecology in these wild
      waterfowl populations. This methodology may be useful in the design of AIV
      surveillance strategies.

PMID- 20688668
TI  - Skin microbial flora and effectiveness of aseptic technique for deep muscle
      biopsies in Weddell seals (Leptonychotes weddellii ) in McMurdo Sound,
      Antarctica.
AB  - Deep muscle biopsies were collected from the pectoralis and longissimus dorsi of
      wild Weddell seals (Leptonychotes weddellii) in McMurdo Sound, Antarctica, during
      October-December 2007. Sterile swabs were collected from the surface of each skin
      site before biopsy and from the deep-needle path after biopsy. No growth occurred
      in two of six pectoralis and three of six longissimus skin sites, or in four of
      10 pectoralis deep biopsy and eight of 12 longissimus deep-biopsy sites. Positive
      skin culture was not predictive of deep-biopsy contamination, nor did
      contamination at one body location correlate with contamination at the second
      site. Psychrobacter species were most common in one or more samples from each of
      the four sample types. Only one of the eight documented bacteria exhibited
      resistance to commonly used antibiotics.

PMID- 20688669
TI  - Serosurveillance for Japanese encephalitis and West Nile viruses in resident
      birds in Hawai'i.
AB  - Japanese encephalitis virus (JEV) and West Nile virus (WNV) are emerging zoonotic
      arboviruses that have recently undergone intercontinental expansion. Both JEV and
      WNV are naturally transmitted between mosquito vectors and vertebrate reservoir
      hosts, including birds. A potential route of JEV introduction from Asia to
      western North America is via the Hawaiian archipelago, while the spread of WNV
      from mainland North America to Hawai'i is also considered an impending threat. We
      surveyed resident, non-native bird sera for antibodies to JEV and WNV on two
      Hawaiian Islands from 2004-2005. Three of 1,835 birds (0.16%) had evidence of
      antiflavivirus antibodies, demonstrating neutralizing activity to JEV and St.
      Louis encephalitis virus (SLEV). These detections could represent a limited
      transmission focus of either, or both, JEV and SLEV, or cross-reactive antibodies
      due to primary infection with an alternate flavivirus. Frequent air traffic from
      both Asia and North America to Hawai'i, along with the presence of probable
      competent vectors and amplifying vertebrate hosts in Hawai'i, increases the
      likelihood of introduction and maintenance of novel flaviviruses. Therefore, it
      is important to monitor for the presence of these viruses.

PMID- 20688670
TI  - Systemic Staphylococcus aureus infection in a free-ranging raccoon (Procyon
      lotor).
AB  - Gross and histopathologic findings are described in an adult male raccoon
      (Procyon lotor) with Staphylococcus aureus infection affecting several organs. At
      the time of necropsy the carcass was jaundiced and in poor nutritional state. A
      large, raised, irregular necrotic mass was present in the spleen. The liver had
      small multifocal, pale yellow, randomly distributed foci throughout the
      parenchyma. Coagulase-positive Staphylococcus aureus was cultured from both the
      liver and the spleen. Microscopic lesions were present in spleen, liver, kidney,
      and heart, which suggested systemic infection. Although S. aureus has been
      cultured from raccoons previously, the bacterium did not appear to have been
      associated with pathology. In this case, S. aureus was obtained as a pure
      culture, but microscopic examination did not show large numbers of bacterial
      colonies as seen in other species with such lesions.

PMID- 20688671
TI  - Polycystic liver disease in senile chamois (Rupicaprae rupicaprae).
AB  - A polycystic disease of the liver was diagnosed in 12 adult, free-living chamois
      (Rupicaprae rupicaprae) from alpine regions in the Western part of Austria. The
      animals (eight female, four male), all in advanced age (average 13 yr old), were
      killed by local hunters, most because of emaciation or abnormal behavior. The
      livers of the animals were enlarged and contained multiple, thin-walled cysts of
      various sizes filled with serous, amber fluid. No evidence for parasites was
      found in the cysts. There were no cysts present in other organs. The cysts were
      lined by a single layer of flattened or low, cubical epithelium indicating
      biliary origin. Except in one case, no fibrosis was found in the adjacent liver
      tissue. In six cases, mild eosinophilic inflammation in the surrounding hepatic
      parenchyma suggested that the cysts could result from previous parasitic
      migration. Although nothing is known regarding heredity, these morphologic
      findings may also indicate an adult type of polycystic disease. To our knowledge,
      this is the first report describing polycystic liver disease in this species.

PMID- 20688672
TI  - Seroprevalance of peste des petits ruminants (PPR) in goitered gazelle (Gazella
      subgutturosa subgutturosa) in Turkey.
AB  - Gazella subgutturosa subgutturosa (goitered gazelle) is a native species of
      Anatolia. Because of the risk of extinction, captured gazelles have been taken
      under protection in a restricted area at the Ceylanpinar state farm, Southeast
      Anatolia, Turkey. Peste des petits ruminants virus (PPRV) infection had been
      detected previously in domestic ruminant species in this region, like in many
      other parts of Turkey. In this study, serum samples from 82 goitered gazelle were
      tested using competitive enzyme-linked immunosorbent assay (c-ELISA). Based on
      the test results, PPRV-specific antibodies were detected in 10 gazelles (12%).
      All c-ELISA-positive sera were confirmed by virus neutralization test.

PMID- 20688673
TI  - Pulmonary lesions caused by the nematode Rhabdias fuscovenosa in a grass snake,
      Natrix natrix.
AB  - In June 2005, a free-ranging grass snake, Natrix natrix infected with Rhabdias
      fuscovenosa was collected for histologic examination of the lungs. Gross lesions
      were not noted; however, histologic examination revealed vacuolar degeneration of
      the respiratory epithelium, hemorrhage, smooth muscle degeneration, faveolae
      necrosis and obstruction, and intralesional nematodes. Eosinophils were the most
      common inflammatory cell observed in the areas of necrosis and interstitium.
      Herein we describe histopathologic changes due to R. fuscovenosa in a free
      ranging grass snake.

PMID- 20688674
TI  - Brucella species survey in polar bears (ursus maritimus) of northern Alaska.
AB  - We report on the presence of specific antibodies to Brucella spp. and Yersinia
      enterocolitica in polar bears (Ursus maritimus) from northern Alaska (southern
      Beaufort Sea) during 2003-2006. Based on numerous known stressors (e.g., climate
      change and loss of sea ice habitat, contaminants), there is increased concern
      regarding the status of polar bears. Considering these changes, it is important
      to assess exposure to potentially pathogenic organisms and to improve
      understanding of transmission pathways. Brucella or specific antibodies to
      Brucella spp. has been reported in marine mammals. Various assays were used to
      elucidate the pathway or source of exposure (e.g., "marine" vs. "terrestrial"
      Brucella spp.) of northern Alaska polar bears to Brucella spp. The standard plate
      test (SPT) and the buffered Brucella antigen card test (BBA) were used for
      initial screening for antibodies specific to Brucella. We then evaluated positive
      reactors (presence of serum antibody specific for Brucella spp.) using
      immunoblots and competitive enzyme-linked immunosorbent assay (cELISA; based on
      pinniped-derived Brucella spp. antigen). Annual prevalence of antibody (BBA and
      SPT) for Brucella spp. ranged from 6.8% to 18.5% over 2003-2006, with an overall
      prevalence of 10.2%. Prevalence of Brucella spp. antibody did vary by age class.
      Western blot analyses indicated 17 samples were positive for Brucella spp.
      antibody; of these, 13 were negative by marine (pinniped) derived Brucella
      antigen cELISA and four were positive by marine cELISA. Of the four samples
      positive for Brucella antibody by marine cELISA, three cross-reacted with Y.
      enterocolitica and Brucella spp. (one sample was Brucella negative and Y.
      enterocolitica positive). It appears the polar bear antibody does not react with
      the antigens used on the marine cELISA assay, potentially indicating a
      terrestrial (nonpinniped) source of Brucella spp.

PMID- 20688675
TI  - Effects of mycoplasmal upper respiratory tract disease on morbidity and mortality
      of gopher tortoises in northern and central Florida.
AB  - Gopher tortoise (Gopherus polyphemus) populations on four tracts of public lands
      in northern and central Florida were studied from 1998 to 2001 to assess the
      effects of mycoplasmal upper respiratory tract disease (URTD). Adult gopher
      tortoises (n=205) were marked for identification, serum and nasal flush samples
      were obtained for mycoplasmal diagnostic assays, and clinical signs of URTD
      (nasal discharge, ocular discharge, palpebral edema, and conjunctivitis) were
      evaluated. A subset of tortoises (n=68) was radio-instrumented to facilitate
      repeated sampling and document potential mortality. Presence of serum antibody to
      Mycoplasma agassizii was determined by enzyme-linked immunosorbent assay (ELISA),
      and mollicutes species were detected in nasal flushes by polymerase chain
      reaction (PCR). Antibody prevalence varied among sites and years but was highest
      in 1998, exceeding 70% at two sites. Only 11 tortoises (5%) were positive by PCR,
      and three species (M. agassizii, M. testudineum, and a nonpathogenic
      Acholeplasma) were identified in nasal flush specimens. Nasal discharge, though
      rare (6% of tortoises), was significantly correlated with higher ELISA ratios,
      study site, and positive PCR status. Mortality events (n=11) occurred on two of
      the three M. agassizii-positive sites; no mortality was observed on the M.
      agassizii-negative control site. However, none of the tested variables (ELISA
      result, study site, year, sex, presence of clinical signs, or carapace length)
      showed significant ability to predict the odds of death. Mycoplasmal URTD is
      believed to be a chronic disease with high morbidity but low mortality, and
      follow-up studies are needed to detect long-term effects.

PMID- 20688676
TI  - Transmission of Mannheimia haemolytica from domestic sheep (Ovis aries) to
      bighorn sheep (Ovis canadensis): unequivocal demonstration with green fluorescent
      protein-tagged organisms.
AB  - Previous studies demonstrated that bighorn sheep (Ovis canadensis) died of
      pneumonia when commingled with domestic sheep (Ovis aries) but did not
      conclusively prove that the responsible pathogens were transmitted from domestic
      to bighorn sheep. The objective of this study was to determine, unambiguously,
      whether Mannheimia haemolytica can be transmitted from domestic to bighorn sheep
      when they commingle. Four isolates of M. haemolytica were obtained from the
      pharynx of two of four domestic sheep and tagged with a plasmid carrying the
      genes for green fluorescent protein (GFP) and ampicillin resistance (AP(R)). Four
      domestic sheep, colonized with the tagged bacteria, were kept about 10 m apart
      from four bighorn sheep for 1 mo with no clinical signs of pneumonia observed in
      the bighorn sheep during that period. The domestic and bighorn sheep were then
      allowed to have fence-line contact for 2 mo. During that period, three bighorn
      sheep acquired the tagged bacteria from the domestic sheep. At the end of the 2
      mo of fence-line contact, the animals were allowed to commingle. All four bighorn
      sheep died 2 days to 9 days following commingling. The lungs from all four
      bighorn sheep showed gross and histopathologic lesions characteristic of M.
      haemolytica pneumonia. Tagged M. haemolytica were isolated from all four bighorn
      sheep, as confirmed by growth in ampicillin-containing culture medium, PCR
      amplification of genes encoding GFP and Ap(R), and immunofluorescent staining of
      GFP. These results unequivocally demonstrate transmission of M. haemolytica from
      domestic to bighorn sheep, resulting in pneumonia and death of bighorn sheep.

PMID- 20688677
TI  - Testing for salmonella spp. In released parrots, wild parrots, and domestic fowl
      in lowland peru.
AB  - Wild animal populations face threats from pathogens from both intentionally
      released captive animals and domestic animals that accompany human settlements.
      From December 2004 through August 2005, we studied free living macaws and parrots
      in the Tambopata National Reserve in the Peruvian Amazon and semicaptive domestic
      fowl in human settlements adjacent to the reserve. In 1992-1993, large macaws
      (Aras spp.) that were serologically positive for Salmonella Pullorum were
      released into this reserve, which hosts dense populations of free-living parrots
      and macaws. We collected cloacal swabs from 64 birds and cultured for Salmonella
      spp. via standard laboratory methods. All 35 psittacines tested were culture
      negative for Salmonella spp., while 31% of 29 domestic fowl were culture
      positive. Our findings suggest that the domestic fowl that accompany human
      settlement in this region carry and shed Salmonella spp. that could threaten wild
      bird populations in and around the reserve.

PMID- 20688678
TI  - Baseline normal values and phylogenetic class of the electrocardiogram of
      anesthetized free-ranging brown bears (Ursus arctos).
AB  - Electrocardiographic (ECG) variables were measured in 22 healthy, free-ranging
      brown bears (Ursus arctos) anesthetized with a combination of medetomidine,
      tiletamine, and zolazepam during research and management operations in south
      central Sweden. Six-limb lead ECGs and the base-apex lead were recorded.
      Morphologies, amplitudes, rhythms, and durations of P waves, PQ intervals, QRS
      complexes, T waves, QT intervals, and QT intervals corrected for heart rate (QTc)
      were calculated from the base-apex lead. The mean electrical axis (MEA) for each
      individual was approximated in the frontal plane from the heights of R waves in
      leads I (X axis) and aVF (Y axis). All 22 bears had sinus rhythms and 10 of them
      had respiratory sinus arrhythmia. Heart rates ranged from 43 to 103 beats per
      minute and were independent of body mass. The MEA was 78.6 (+ or - 5.5) degrees.
      Some bears had strikingly peaked T waves, and many had pronounced notching (high
      frequency components) to the QRS complex. This information contributes to the
      limited data base of electrocardiography for brown bears and elucidates ECG
      similarities with other species in the order Carnivora.

PMID- 20688679
TI  - Reference intervals for plasma biochemical and hematologic measures in loggerhead
      sea turtles (Caretta caretta) from Moreton Bay, Australia.
AB  - Biochemical and hematologic reference intervals have been reported for loggerhead
      sea turtles (Caretta caretta, Linnaeus 1758), but low sample numbers and simple
      statistical analyses have constrained their diagnostic usefulness. During June
      2007-May 2008, 101 loggerhead sea turtles in Moreton Bay, Queensland, Australia,
      were captured by hand from boats; clinically assessed to determine health status;
      blood was sampled; and biochemical and hematologic variables were measured. Of
      these turtles, 66 were classified as clinically healthy and 23 as unhealthy.
      Reference intervals were calculated using data from clinically healthy turtles.
      Of the clinically unhealthy turtles, 82 and 45% had at least one biochemical and
      hematologic result, respectively, outside of at least one of the calculated
      intervals. However, only low proportions of unhealthy loggerhead sea turtles had
      abnormal results for each variable. The highest percentage of unhealthy turtles
      that were outside at least one estimated reference interval was 35%, for
      thrombocyte counts. Neither sex nor maturity category (mature versus large
      immature) influenced the risk of being clinically unhealthy. These are the first
      plasma biochemical and hematologic reference intervals reported for loggerhead
      sea turtles from the southwestern Pacific Ocean. We conclude that, for loggerhead
      sea turtles in Moreton Bay, separate reference intervals are required for mature
      and immature turtles for thrombocyte counts and for male and female turtles for
      lymphocyte, heterophil, and total white cell counts; otherwise, a single
      reference interval can be used regardless of age or sex. When estimating
      reference intervals in loggerhead sea turtles, it is desirable to use both
      methods for calculating reference intervals used in this study because intervals
      can differ substantially between methods for some variables. Joint interpretation
      using reference intervals from both methods allows the categorization of results
      as "normal," "suspect," or "abnormal."

PMID- 20688680
TI  - Survey for antibodies to infectious bursal disease virus serotype 2 in wild
      turkeys and Sandhill Cranes of Florida, USA.
AB  - Captive-reared Whooping Cranes (Grus americana) released into Florida for the
      resident reintroduction project experienced unusually high mortality and
      morbidity during the 1997-98 and 2001-02 release seasons. Exposure to infectious
      bursal disease virus (IBDV) serotype 2 as evidenced by seroconversion was
      suspected to be the factor that precipitated these mortality events. Very little
      is known about the incidence of IBD in wild bird populations. Before this study,
      natural exposure had not been documented in wild birds of North America having no
      contact with captive-reared cranes, and the prevalence and transmission
      mechanisms of the virus in wild birds were unknown. Sentinel chickens (Gallus
      gallus) monitored on two Whooping Crane release sites in central Florida, USA,
      during the 2003-04 and 2004-05 release seasons seroconverted, demonstrating
      natural exposure to IBDV serotype 2. Blood samples collected from Wild Turkeys
      (Meleagris gallopavo) and Sandhill Cranes (Grus canadensis) in eight of 21
      counties in Florida, USA, and one of two counties in southern Georgia, USA, were
      antibody-positive for IBDV serotype 2, indicating that exposure from wild birds
      sharing habitat with Whooping Cranes is possible. The presence of this virus in
      wild birds in these areas is a concern for the resident flock of Whooping Cranes
      because they nest and raise their chicks in Florida, USA. However, passively
      transferred antibodies may protect them at this otherwise vulnerable period in
      their lives.

PMID- 20688681
TI  - Bovine tuberculosis in Ethiopian wildlife.
AB  - Bovine tuberculosis (BTB) is endemic in Ethiopian cattle. However, the status of
      the disease in wildlife populations that often share habitat with livestock is
      unknown. We screened for BTB in wildlife in five regions in Ethiopia. Blood and
      tissue samples from 133 mammals of 28 species were collected from 2006 to 2008.
      We used a rapid serology test (RT) based on lateral flow technology, and
      performed culture of lymph node specimens inoculated onto Lowenstein-Jensen and
      Middlebrook 7H11 media. Acid-fast colonies were further analyzed by molecular
      typing. Sera from 20 of 87 animals (23%) were positive for BTB by RT; acid-fast
      bacilli were cultured from 29 of 89 animals (32.5%). None of the positive
      cultures yielded mycobacteria from the Mycobacterium tuberculosis complex but
      many environmental mycobacteria were isolated. Among these, Mycobacterium terrae
      was the most common. We demonstrated a high prevalence of environmental
      mycobacteria in wildlife, the role of which is unknown. Flagship rare endemic
      species such as the mountain nyala (Tragelaphus buxtoni) and the Ethiopian wolf
      (Canis simensis) may be at risk for BTB. We also assessed the utility of RT for
      field purposes.

PMID- 20688682
TI  - Mortality during epizootics in bighorn sheep: effects of initial population size
      and cause.
AB  - One of the most severe threats to bighorn sheep (Ovis canadensis) populations is
      disease. With the objective of projecting possible epizootic consequences to
      bighorn sheep population dynamics, we examined 23 epizootic mortality episodes
      from presumably known causes that occurred in the United States and Canada from
      1942 to 2005. These outbreaks were correlated with population size using
      regression models. Epizootic origins were documented by considering contact with
      a "new" pathogen for the bighorn sheep population or pneumonic processes,
      presumably triggered by stress. We suggest mortality rates are negatively related
      to population size in a logarithmic function, and offer a model to estimate the
      percentage of disease-related mortalities for a given population size of bighorn
      sheep. From a disease dynamics perspective, we suggest a minimum population of
      188 bighorn sheep would be required to insure long-term persistence in the
      presence of epizootic disease.

PMID- 20688683
TI  - Health assessment of American Oystercatchers (Haematopus palliatus palliatus) in
      Georgia and South Carolina.
AB  - The American Oystercatcher (Haematopus palliatus palliatus) is the only species
      of oystercatcher native to the Atlantic coast of North America and is restricted
      in distribution to intertidal shellfish beds in coastal areas. Currently, the
      American Oystercatcher population in South Carolina and Georgia is threatened by
      widespread habitat loss, resulting in low reproductive success and small
      population size. Oystercatchers could be an important indicator of ecosystem
      health because they depend on quality coastal breeding habitat and prey on
      bivalves, which can accumulate toxins and pathogens from the local environment.
      Data were collected from American Oystercatchers (n=171) captured at five sites
      in South Carolina and Georgia between 2001 and 2006. Iridial depigmentation was
      frequently noted during physical examination and was more prevalent in female
      birds. Female birds were larger than males on average, but ranges for weight and
      morphometric measurements had considerable overlap. Mean values were calculated
      for hematology, plasma biochemistry, and hormone levels, and prevalence of
      exposure to select pathogens was determined. Mercury was the only trace metal
      detected in blood samples. These data provide baseline health information needed
      for longitudinal monitoring and conservation efforts for American Oystercatchers.
      In addition, this study illustrates the potential use of this species as an
      indicator for the health of the southeastern US coastal nearshore ecosystem.

PMID- 20688684
TI  - Seasonal prevalence of serum antibodies to whole cell and recombinant antigens of
      Borrelia burgdorferi and Anaplasma phagocytophilum in white-tailed deer in
      Connecticut.
AB  - Whole-blood samples were obtained from 214 white-tailed deer (Odocoileus
      virginianus) representing 44 sites in Connecticut (USA) during 1992, 1993, 1996,
      1999, and 2000 through 2006. Sera were analyzed for total antibodies to whole
      cell or recombinant antigens of Borrelia burgdorferi sensu stricto and Anaplasma
      phagocytophilum, the respective causative agents of Lyme borreliosis and human
      granulocytic anaplasmosis. Deer sera contained antibodies to both bacteria during
      different seasons and throughout the 11-yr study. Of the 224 sera tested, 141
      (63%) contained antibodies to whole-cell B. burgdorferi in a polyvalent enzyme
      linked immunosorbent assay, whereas 124 (55%) were positive to whole-cell A.
      phagocytophilum by indirect fluorescent antibody staining. Use of highly specific
      recombinant antigens (VlsE of B. burgdorferi and protein 44 of A.
      phagocytophilum) provided strong confirmatory results of past or current
      infections. There was coexistence of antibodies to whole-cell or recombinant
      antigens of both agents in 72 (32%) sera. Analyses of 18 sera from eight deer
      that were marked, released, and recaptured, showed minimal changes in antibody
      titer over sampling time intervals ranging from 17 days to 5.1 yr. Relatively
      high antibody prevalences for both bacterial agents in different seasons and
      years reaffirm that there are well-established foci for both tick-borne
      infections and probably reflect frequent exposure of deer to infected Ixodes
      scapularis ticks. November and December is a suitable period to obtain blood
      samples from deer to conduct serosurveillance for both bacteria.

PMID- 20688685
TI  - Real-time PCR detection of Campylobacter spp. In free-ranging mountain gorillas
      (Gorilla beringei beringei).
AB  - Health monitoring of wildlife populations can greatly benefit from rapid, local,
      noninvasive molecular assays for pathogen detection. Fecal samples collected from
      free-living Virunga mountain gorillas (Gorilla beringei beringei) between August
      2002 and February 2003 were tested for Campylobacter spp. DNA using a portable,
      real-time polymerase chain reaction (PCR) instrument. A high prevalence of
      Campylobacter spp. was detected in both individually identified (22/26=85%) and
      nest-collected samples (68/114=59.6%), with no statistically significant
      differences among different gorilla sexes or age classes or between tourist
      visited versus research gorilla groups. The PCR instrument was able to
      discriminate two distinct groups of Campylobacter spp. in positive gorilla
      samples based on the PCR product fluorescent-probe melting profiles. The rare
      type (6/90 positives, 7%, including three mixed cases) matched DNA sequences of
      Campylobacter jejuni and was significantly associated with abnormally soft
      stools. The more common type of positive gorilla samples (87/90 positives, 97%)
      were normally formed and contained a Campylobacter sp. with DNA matching no
      published sequences. We speculate that the high prevalence of Campylobacter spp.
      detected in gorilla fecal samples in this survey mostly reflects previously
      uncharacterized and nonpathogenic intestinal flora. The real-time PCR assay was
      more sensitive than bacterial culture with Campylobacter-specific media and
      commercially available, enzyme immunoassay tests for detecting Campylobacter spp.
      in human samples.

PMID- 20688686
TI  - Experimental infection in lambs with a red deer (Cervus elaphus) isolate of
      Anaplasma phagocytophilum.
AB  - Anaplasma phagocytophilum transmitted by Ixodes spp. ticks is the causative agent
      of tick-borne fever (TBF) in domestic ruminants. TBF is widespread along the
      coast of southern Norway and may cause a severe problem for the sheep industry.
      Red deer (Cervus elaphus) are important hosts for ticks and have been found to be
      infected naturally with A. phagocytophilum. However, it is unclear whether red
      deer could serve as reservoir hosts for A. phagocytophilum infections in sheep.
      We infected lambs experimentally with a red deer and a sheep isolate,
      respectively. The 497 base pairs of the partial 16S rRNA gene sequences of both
      isolates were 100% identical to GenBank accession number M73220; the 3.8
      kilobases of the total ank gene sequences were 99% identical. Sixteen lambs were
      used, four lambs in each group. Two groups were inoculated with the red deer
      isolate on day 0, and then challenged on day 42 with the ovine or the red deer
      isolate, respectively. The third group was inoculated with the sheep isolate on
      day 0 and challenged with the red deer strain on day 42. Four lambs were used as
      uninfected controls. Blood samples for hematology, bacteriology, and serology
      were collected regularly for 12 wk. Presence of A. phagocytophilum in blood was
      determined using blood smears. Serologic response was measured by indirect
      immunofluorescence. Although animals inoculated with the ovine strain showed more
      severe clinical manifestations, lambs infected with the red deer isolate reacted
      with typical signs of TBF such as fever, bacteremia, and neutropenia. We conclude
      that A. phagocytophilum strains causing TBF in sheep might circulate in the red
      deer population in Norway.

PMID- 20688687
TI  - The dusky-footed woodrat (Neotoma fuscipes) is susceptible to infection by
      Anaplasma phagocytophilum originating from woodrats, horses, and dogs.
AB  - The dusky-footed woodrat (Neotoma fuscipes) is the putative reservoir for
      Anaplasma phagocytophilum in the western United States based on high prevalence
      of A. phagocytophilum genetic material detected by polymerase chain reaction
      (PCR), high antibody prevalence, and infestation with the vector tick Ixodes
      pacificus. Following inoculation of nine wild-caught woodrats with woodrat-,
      canine-, or equine-origin A. phagocytophilum, all became PCR-positive and
      seroconverted. However, when PCR-positive woodrat blood was delivered as inoculum
      to three horses, the horses never became clinically ill, PCR-positive, or
      antibody-positive. Each horse was subsequently infected with either the equine-
      or chipmunk-origin A. phagocytophilum, resulting in clinical anaplasmosis. Our
      data show that woodrats are permissive to several strains of A. phagocytophilum,
      but strains originating from woodrats did not cause clinical disease in horses.

PMID- 20688688
TI  - Field evaluation of an inactivated vaccine to control raccoon rabies in Ontario,
      Canada.
AB  - Since raccoon rabies first appeared in Ontario in 1999, >90,000 raccoons (Procyon
      lotor) have received IMRAB3 inactivated rabies vaccine via intramuscular (IM)
      injection and were released at the point of capture as part of a multiyear rabies
      control program, trap-vaccinate-release (TVR). Of the 132 confirmed cases
      infected with raccoon-variant rabies virus in Ontario between 1999 and 2005, two
      were from that vaccinated group, as indicated by the presence of identifying ear
      tags. During ongoing rabies control programs in 2003, sera were collected from
      172 wild raccoons that had received IMRAB3 and tested for rabies-virus
      antibodies. Raccoons had one of three histories: 1) vaccinated in the current
      year only (to examine the response to primary vaccination), 2) vaccinated in the
      previous year only (to determine the duration of the primary antibody response),
      and 3) vaccinated in the previous year and current year (to examine antibody
      response to booster vaccination). Seroconversion in primary vaccinates could be
      detected as early as 1 wk postvaccination when sera were measured with the use of
      a competitive enzyme-linked immunosorbent assay (C-ELISA) with a cutoff value
      established to correspond to a neutralizing titer of 0.5 IU/ml. During weeks
      three and four postvaccination, 94% of sampled raccoons had detectable antibodies
      to rabies virus and 31% were still antibody positive the following year.
      Differences in the kinetics of the immune response were found in raccoons sampled
      from the two different TVR areas of the province. A strong anamnestic response
      was detected after booster vaccinations. IMRAB3 by IM injection was found to be
      an efficacious vaccine for rabies control in raccoons.

PMID- 20688689
TI  - Identification of Euryhelmis costaricensis metacercariae in the skin of Tohoku
      hynobiid salamanders (Hynobius lichenatus), northeastern Honshu, Japan.
AB  - Since 2000, cutaneous nodular lesions were observed in Tohoku hynobiid
      salamanders (Hynobius lichenatus) in the northern Abukuma Mountains, northeastern
      Honshu, Japan. The distribution of diseased salamanders has expanded, along with
      the increasing severity of the disease. Samples (foreleg, hindleg, and tail) from
      five diseased salamanders caught in the spring of 2009 contained 11 to 383
      metacercarial cysts (0.43-0.48 mm in diameter) per individual. Experimental
      inoculations of the metacercariae into rats (Rattus norvegicus) resulted in the
      development of pentagonal adults with intrauterine eggs that were collected at 3
      days, 2 wk, and 5 wk postinoculation. Although adults obtained from rats were
      smaller, the flukes were morphologically similar to Euryhelmis costaricensis,
      recorded from Japanese martens (Martes melampus) in northeastern Honshu. The
      ribosomal RNA gene sequences of the metacercariae collected from salamanders and
      the E. costaricensis collected from a Japanese marten were identical, confirming
      the morphology-based species identification. Environmental changes responsible
      for the increased frequency of diseased salamanders and the increased parasite
      load are unknown, although increases in feral populations of introduced raccoons
      (Procyon lotor) and American minks (Neovison vison) may be associated.

PMID- 20688690
TI  - Baylisascaris procyonis in raccoons in Texas and its relationship to habitat
      characteristics.
AB  - Raccoons (n=590) were collected from October 1999 to August 2003 from 35 counties
      across Texas, USA, and gastrointestinal tracts were examined for Baylisascaris
      procyonis. We documented B. procyonis in central and eastern Texas. Baylisascaris
      procyonis occurred in 5.4% raccoons in Texas with an overall mean abundance and
      mean intensity of 0.4+/-0.1 and 7.4+/-2.3, respectively. Prevalence was higher in
      central Texas ecoregions and on clayey soil texture than other regions or soil
      textures of Texas. Mean parasite abundance was highest in the Postoak Savanna
      ecoregion located in central Texas. Our findings expanded the range of B.
      procyonis in Texas and confirmed that areas of Texas with clayey soil texture are
      more vulnerable to B. procyonis transmission. This study gives a better
      understanding of where B. procyonis may occur in Texas and which environmental
      characteristics are better suited for B. procyonis occurrence and transmission,
      especially in areas where likelihood of frequent human contact with raccoons and
      their feces increases.

PMID- 20688691
TI  - Lead toxicity in captive and wild Mallards (Anas platyrhynchos) in Spain.
AB  - Forty captive Mallards (Anas platyrhynchos), of both sexes, were separated into
      five groups and dosed with lead shot via oral intubation; one group was used as a
      control. Lead dosage differed in terms of shot number and size, as well as
      administration time. One hundred and thirty-five wild mallards were trapped
      between 1998 and 2001 in the Boada and Nava lagoons near the Canal de Castilla,
      in the Spanish province of Palencia. Radiologic techniques (ventrodorsal and
      lateral views) were used to detect lead shot in the gizzard and to determine
      degradation in dosed birds over time. Heparinized blood samples were taken from
      wild and captive mallards and blood lead levels were determined using anodic
      stripping voltammetry with a dropping mercury electrode. Clinical signs,
      injuries, and body weight were recorded. In approximately 90% of the
      experimentally dosed mallards, administered shot stayed in their gizzard until it
      degraded; this took approximately 30 days. Peak lead levels in blood were
      observed between days 10 and 20, and 10 days following a repeat dosage; males
      were more sensitive than females to a repeat dosage. During the experimental
      phase, 34% of birds died, and those that survived had varying degrees of
      anorexia, lethargy, and a decreased response to external stimulus. Of 135 tested
      wild mallards, 41% had a blood lead concentration higher than 0.200 microg/g.
      Lead shot was found embedded in 3.6% of the wild birds and 1.2% had a lead shot
      pellet in their gizzard.

PMID- 20688692
TI  - Survival of radio-marked mallards in relation to management of avian botulism.
AB  - Avian botulism outbreaks are frequently perpetuated by type C toxin produced by
      Clostridium botulinum proliferating in decomposing bird carcasses and consumption
      of toxic maggots from these carcasses by healthy birds. Therefore, removing bird
      carcasses has been advocated for disease management because availability of toxic
      maggots should be reduced, increasing duck survival. However, this management is
      expensive, and its effect on waterfowl mortality under field conditions is
      unknown. We radio-marked 419 molting mallards on 11 lakes in western Canada
      during July-August 1999-2001 and monitored them for 30 days, testing whether
      survival was higher on lakes with carcass removal. Botulism occurred on 10 lakes.
      On five carcass removal lakes, greater-than-normal effort was made to conduct
      early, thorough surveillance and immediately remove carcasses; on six nonremoval
      lakes, no carcasses were removed. In 1999, estimated 30-day survival
      probabilities ranged from 0.149 (95% CI=0.065-0.304) on one large lake with
      carcass removal to 0.466 (95% CI=0.270-0.674) and 0.618 (95% CI=0.443-0.767) on
      two nonremoval lakes. As a result, we conducted work on smaller wetlands
      thereafter, reasoning that any management benefit would be easier to detect. In
      2000, estimated 30-day survival probabilities were 0.313 (95% CI=0.143-0.556) and
      0.794 (95% CI=0.609-0.905) on two carcass removal lakes versus 0.525 (95%
      CI=0.362-0.682) and 0.743 (95% CI=0.564-0.866) on two nonremoval lakes. In 2001,
      botulism was detected on two nonremoval lakes where survival probabilities were
      0.845 (95% CI=0.630-0.946) and 0.942 (95% CI=0.778-0.987), and on one removal
      lake where survival probability was 1.0 (95% CI=0.99-1.0), but not detected on
      the other removal lake where no marked birds died from botulism (1.0, 95% CI=0.99
      1.0). Survival tended to be higher on lakes with lower carcass density, but when
      data were organized by carcass removal versus nonremoval, mallard survival was
      not consistently greater on lakes where carcasses were removed.

PMID- 20688693
TI  - Surveillance of avian influenza virus in wild bird fecal samples from South
      Korea, 2003-2008.
AB  - We analyzed the results from nationwide surveillance of avian influenza (AI) from
      birds in South Korea's major wild bird habitats and the demilitarized zone of
      South Korea, 2003-2008. Of 28,214 fecal samples analyzed, 225 yielded influenza
      viruses, for a prevalence of 0.8%. Hemagglutinin (HA) subtypes H1-H12 and all
      nine neuraminidase (NA) subtypes were detected. The dominant HA subtypes were H6,
      H1, and H4, and the most common NA subtypes were N2, N1, and N6. Among the 38
      HA/NA subtype combinations, the most common were H4N6, H6N1, and H5N2. Thirty
      seven low-pathogenic AI (LPAI) viruses of the H5 and H7 subtype were detected.
      Among them, we identified bird species for 16 H5- and H7-positive fecal samples
      using a DNA bar-coding system instituted in 2007; all birds were identified as
      Anseriformes. The HA gene of the H5 wild bird isolates belonged to the Eurasian
      avian lineage, and could be clearly distinguished from the sublineage H5N1 highly
      pathogenic AI (HPAI) of the Eurasian and American avian lineages. Whereas H7 LPAI
      viruses did not group as a separate sublineage with H7 HPAI viruses, H7 isolates
      were closely related with the Eurasian avian lineage.

PMID- 20688694
TI  - Occurrence of west nile virus infection in raptors at the Salton Sea, California.
AB  - We investigated the prevalence of West Nile virus (WNV)-neutralizing antibodies
      and infectious virus, and the occurrence of overwinter transmission in two raptor
      species during January and March 2006 at the Salton Sea, Imperial County,
      California. We captured 208 American Kestrels (Falco sparverius) (January, n=100;
      March, n=108) and 116 Burrowing Owls (Athene cunicularia) (January, n=52; March,
      n=64). Laboratory analysis revealed that 83% of American Kestrels and 31% of
      Burrowing Owls were positive for WNV-neutralizing antibodies. Additionally, two
      seroconversions were detected in Burrowing Owls between January and March.
      Infectious WNV, consistent with acute infection, was not detected in any bird.

PMID- 20688695
TI  - Prevalence of antibodies to type a influenza virus in wild avian species using
      two serologic assays.
AB  - Serologic testing to detect antibodies to avian influenza (AI) virus has been an
      underused tool for the study of these viruses in wild bird populations, which
      traditionally has relied on virus isolation and reverse transcriptase-polymerase
      chain reaction (RT-PCR). In a preliminary study, a recently developed commercial
      blocking enzyme-linked immunosorbent assay (bELISA) had sensitivity and
      specificity estimates of 82% and 100%, respectively, for detection of antibodies
      to AI virus in multiple wild bird species after experimental infection. To
      further evaluate the efficacy of this commercial bELISA and the agar gel
      immunodiffusion (AGID) test for AI virus antibody detection in wild birds, we
      tested 2,249 serum samples collected from 62 wild bird species, representing 10
      taxonomic orders. Overall, the bELISA detected 25.4% positive samples, whereas
      the AGID test detected 14.8%. At the species level, the bELISA detected as many
      or more positive serum samples than the AGID in all 62 avian species. The
      majority of positive samples, detected by both assays, were from species that use
      aquatic habitats, with the highest prevalence from species in the orders
      Anseriformes and Charadriiformes. Conversely, antibodies to AI virus were rarely
      detected in the terrestrial species. The serologic data yielded by both assays
      are consistent with the known epidemiology of AI virus in wild birds and
      published reports of host range based on virus isolation and RT-PCR. The results
      of this research are also consistent with the aforementioned study, which
      evaluated the performance of the bELISA and AGID test on experimental samples.
      Collectively, the data from these two studies indicate that the bELISA is a more
      sensitive serologic assay than the AGID test for detecting prior exposure to AI
      virus in wild birds. Based on these results, the bELISA is a reliable species
      independent assay with potentially valuable applications for wild bird AI
      surveillance.

PMID- 20688697
TI  - Confirmation of Bacillus anthracis from flesh-eating flies collected during a
      West Texas anthrax season.
AB  - This case study confirms the interaction between necrophilic flies and white
      tailed deer, Odocoileus virginianus, during an anthrax outbreak in West Texas
      (summer 2005). Bacillus anthracis was identified by culture and PCR from one of
      eight pooled fly collections from deer carcasses on a deer ranch with a well
      documented history of anthrax. These results provide the first known isolation of
      B. anthracis from flesh-eating flies associated with a wildlife anthrax outbreak
      in North America and are discussed in the context of wildlife ecology and anthrax
      epizootics.

PMID- 20688696
TI  - An outbreak of type C botulism in waterbirds: Incheon, Korea.
AB  - Five outbreaks of botulism in waterbirds were encountered over a 5-yr period from
      2004 to 2008 in Korea. In October 2008, an outbreak of avian type C botulism
      affected approximately 2,000 wild waterbirds in the Namdong flood control basin,
      Incheon, South Korea. Ecologic conditions, clinical signs exhibited by moribund
      birds, and lack of gross pathology and microbial evidence of infectious disease,
      suggested botulinum intoxication. Type C botulinum toxin was demonstrated in duck
      sera, liquid culture of intestinal tissue, and an extract of maggots taken from
      the carcasses. Additionally, 34 of 40 (85.0%) sediment samples from the same area
      were positive for botulinum toxin by mouse bioassay using multivalent (types A-F)
      antiserum, indicating that toxigenic Clostridium botulinum was present in the
      environment. This is the most severe case of avian botulism documented in Korea.

PMID- 20688698
TI  - Haloperidol and azaperone in drive-net captured Southern chamois (Rupicapra
      pyrenaica).
AB  - We investigated the effect of haloperidol and azaperone in drive-net captured
      Southern chamois (Rupicapra pyrenaica). Both tranquilizers have been successfully
      used in a wide range of wild species for reducing postcapture stress response.
      During 2005, 39 free-ranging chamois were captured, randomly injected
      intramuscularly with haloperidol (0.29 +/- 0.12 mg/kg; n=24), azaperone (1.1 +/-
      0.82 mg/kg; n=6), or saline (0.5 ml; n=9), and restrained for 3 hr. Heart rate
      was higher in the treated chamois; erythrocyte parameters and total protein
      concentration decreased over time owing to splenic sequestration, hemodilution,
      vasodilation, and reflex tachycardia. Creatinine, sodium, and chloride remained
      stable only in the haloperidol-treated group, suggesting an improvement in renal
      perfusion. Nevertheless, the azaperone-treated chamois displayed higher body
      temperature, and both treated groups had higher serum muscular enzymes than the
      control group, suggesting higher muscle stress. These results lead us not to
      recommend the use of these tranquilizers-especially azaperone-as first-choice
      neuroleptics in chamois.

PMID- 20688699
TI  - Optimization of Raccoon latrine surveys for quantifying exposure to Baylisascaris
      procyonis.
AB  - Raccoon (Procyon lotor) latrine surveys are an efficient and cost-effective
      method to quantify Baylisascaris procyonis exposure risk for intermediate hosts.
      Nevertheless, current methodologies may introduce bias by homogenizing scats
      collected within latrines and estimating exposure risk at the latrine scale. The
      objective of this study was to examine the potential for raccoon latrine size to
      bias estimates of risk of exposure when utilizing current methodologies that pool
      scats prior to analysis. We accomplished this by evaluating correlation of the
      presence of B. procyonis eggs among scats collected within latrines. Specimens
      were collected in southern Indiana during November and December of 2006. Raccoon
      scats collected within latrines exhibited no correlation with the presence of B.
      procyonis eggs. Accordingly, to eliminate the bias introduced by pooling scats
      within latrines, scats rather than latrines should be treated as the sampling
      unit for estimating risk of exposure for intermediate hosts. Further, evaluation
      of exposure risk based on individual scats has the potential to greatly reduce
      the time and expense associated with obtaining precise estimates of B. procyonis
      exposure risk.

PMID- 20688700
TI  - Detection of Hypoderma actaeon infestation in Cervus elaphus with ELISA and
      western blotting.
AB  - We used enzyme-linked immunosorbent assay (ELISA) and western blotting (WB) to
      evaluate the reactivity of first-stage larval extracts of Hypoderma lineatum with
      antibodies in sera from 76 red deer from an endemic area for Hypoderma actaeon.
      Antibodies in sera from deer infested with H. actaeon recognized hypodermin C
      from H. lineatum in both ELISA and WB assays. ELISA values were correlated with
      the epidemiology of the fly infestation in the area where the deer sera were
      collected. There was no clear relationship between anti-hypodermin C antibody
      levels and the age of the animals or the number of Hypoderma grubs found at
      necropsy in the hides of the deer. Our results suggest that first-instar antigens
      of H. lineatum can be used to diagnose natural infestations by H. actaeon by
      indicating the presence of first-stage larvae, which can help to accurately
      describe H. actaeon epidemiology.

PMID- 20688701
TI  - Survey for foot-and-mouth disease in the endangered marsh deer (Blastocerus
      dichotomus) from marshlands of the Parana River Basin, Brazil.
AB  - Habitat fragmentation and diseases have resulted in a decline of the marsh deer
      (Blastocerus dichotomus) throughout its South American range. Our objectives were
      to determine whether marsh deer intended for translocation from a region of the
      Rio Parana Basin had been infected previously by foot-and-mouth disease virus
      (FMDV) and whether they were carrying virus. We captured marsh deer from June to
      October 1998 and collected blood from 108 animals and esophageal-pharyngeal fluid
      from 53. Serum was tested for antibodies against three FMDV serotypes (O, A, and
      C) by liquid-phase-blocking sandwich enzyme-linked immunosorbent assay (ELISA).
      Esophageal-pharyngeal fluid was tested for FMDV RNA by reverse transcription
      polymerase chain reaction (RT-PCR) and inoculation into three successive baby
      hamster kidney (BHK-21) cell subcultures, followed by RT-PCR of cultures. We
      detected low log(10) titers (range 1.0-1.5) to FMDV subtype A(24) Cruzeiro in 19
      of 108 sampled marsh deer, but failed to isolate FMDV or detect FMDV RNA in any
      samples. We conclude that marsh deer from our study site were unlikely to carry
      FMDV; however, as a preventive measure, the 19 animals with titers for FMDV were
      not sent to FMDV-free Brazilian states.

PMID- 20688702
TI  - Survey of Escherichia coli O157 in captive frogs.
AB  - To evaluate the presence of Escherichia coli O157, cloacal swabs were collected
      from 60 adult frogs kept as pets and analyzed by culture methods and multiplex
      polymerase chain reaction for stx1, stx2, and E. coli attaching and effacing
      (eae) and hly genes. The pathogen was isolated from two samples and both carried
      stx2 gene. This is believed to be the first report of natural E. coli O157
      infection in living frogs.

PMID- 20688703
TI  - Prevalence of selected vector-borne organisms and identification of Bartonella
      species DNA in North American river otters (Lontra canadensis).
AB  - Trapper-killed North American river otters (Lontra canadensis) in North Carolina,
      USA, were screened for multiple vector-borne bacteria known to be pathogenic to
      mammals. Blood was collected from 30 carcasses in 2006, from 35 in 2007, and from
      one live otter in 2008. Samples were screened using conventional polymerase chain
      reaction (PCR) tests for DNA from Bartonella spp., Ehrlichia spp., and spotted
      fever group Rickettsia spp. All samples were negative for Rickettsia spp. Twelve
      of 30 samples from 2006 produced amplicons using the assay designed to detect
      Ehrlichia spp., but sequencing revealed that the amplified DNA fragment was from
      a novel Wolbachia sp., thought to be an endosymbiote of a Dirofilaria sp. Between
      2006 and 2007, DNA from a novel Bartonella sp. was detected in 19 of 65 animals
      (29%). Blood from one live otter captured in 2008 was found positive for this
      Bartonella sp. by both PCR and culture. The pathogenicity of this Bartonella
      species in river otters or other mammals is unknown.

PMID- 20688704
TI  - Outbreak of botulism (Clostridium botulinum type C) in wild waterfowl: Seoul,
      Korea.
AB  - Over a 6-day period beginning on 15 October 2008, 93 dead or sick wild waterfowl,
      including Mallards, Spotbills, and teal species, were found along the shore of a
      branch stream of the Hangang River, which flows through Seoul, Korea, and were
      submitted to the National Veterinary Research and Quarantine Service (NVRQS) for
      diagnosis. Clinically, the affected birds showed flaccid paralysis of the legs
      and wings and paralysis of the neck. Grossly, no bird showed any lesions, but all
      had almost empty stomachs. Histopathologic findings included mild lymphocytic
      hepatitis and mild lymphocytic interstitial nephritis. Clostridium botulinum type
      C toxin was identified in sera collected from the birds using a mouse bioassay
      for botulinum toxins; however, no bacteria were isolated from any of the affected
      birds. In addition, a low-pathogenic avian influenza virus was isolated from two
      Spotbills, and pesticides such as diazinon and phorate, were detected in seven
      Mallards. The cause of this outbreak is not clear, but an increase in organic
      materials from sewage due to drought, increased temperatures, and an increased
      number of aquatic carcasses resulting from pesticide contamination may have
      increased the replication of C. botulinum, contributing to the release of
      botulinum toxins into the waterfowl food chain.

PMID- 20688705
TI  - First report of Hepatozoon sp. in the Oregon spotted frog, Rana pretiosa.
AB  - From 2005 through 2008, we screened 650 Oregon spotted frogs (Rana pretiosa) from
      three populations in central Oregon, USA, for hemoparasites. A Hepatozoon sp.,
      not previously reported in R. pretiosa, was found in one population of frogs,
      mostly as intracellular gamonts at a prevalence of 10.5% with parasitemias
      ranging from 0.02% to greater than 42% of erythrocytes within individual frogs.
      Intra-and extracellular merozoites were present, but rare. A potential vector,
      the mosquito Culex boharti, was common throughout the habitat of the population
      carrying Hepatozoon sp.

PMID- 20688706
TI  - Bilateral complex microphthalmia with intraocular dermoid cyst in a neonate red
      deer (Cervus elaphus).
AB  - A 3-day-old, male red deer (Cervus elaphus) with bilateral microphthalmia was
      found dead in the Western Alps in northern Italy. No other gross alterations were
      present. Ocular globes were formalin fixed and processed for histology. In both
      eyes, a large cyst, filled with keratin and lined by squamous epithelium admixed
      with sebaceous glands and hair follicles, expanded the anterior chamber. A mass
      composed of spindle cells and small tubules, embedded in myxoid ground substance,
      filled the vitreal chamber. No lens tissue was found, leading to the speculation
      that the dermoid cystic structures originated from abnormal differentiation of
      the primitive ectodermal lens vesicle. Immunohistochemistry with a panel of
      antibodies against cytoskeletal proteins revealed neural and mesenchymal elements
      within the vitreal mass. A complex bilateral ocular dysgenesis, with
      microphthalmia, aphakia, and dermoid metaplasia of primitive lens vesicle was
      diagnosed. The latter finding was unusual and was previously documented only in
      Texel sheep (Ovis ammon), in which it was related to specific gene mutation on
      chromosome 23.

PMID- 20688707
TI  - Effectiveness of rapid diagnostic tests to assess pathogens of fishers (Martes
      pennanti) and gray foxes (Urocyon cinereoargenteus).
AB  - Wildlife managers often need to assess the current health status of wildlife
      communities before implementation of management actions involving surveillance,
      reintroductions, or translocations. We estimated the sensitivity and specificity
      of a commercially available domestic canine rapid diagnostic antigen test for
      canine parvovirus and a rapid enzyme-linked immunosorbent assay for the detection
      of antibodies toward Anaplasma phagocytophilum on populations of fishers (Martes
      pennanti) and sympatric gray foxes (Urocyon cinereoargenteus). Eighty-two fecal
      samples from 66 fishers and 16 gray foxes were tested with both SNAP((R)) PARVO
      rapid diagnostic test (RDT) and a nested polymerase chain reaction (PCR). Whole
      blood samples from 23 fishers and 53 gray foxes were tested with both SNAP 4Dx
      RDT and immunofluorescence assays (IFAs). The SNAP PARVO RDT detected no
      parvovirus, whereas PCR detected the virus in 17 samples. Eleven samples were
      positive using the SNAP 4Dx RDT, whereas 46 samples tested by IFA were positive
      for A. phagocytophilum. Both RDTs had low sensitivity and poor test agreement.
      These findings clearly demonstrate the importance of validating RDTs developed
      for domesticated animals before using them for wildlife populations.

PMID- 20688708
TI  - Prevalence of hypermucoid Klebsiella pneumoniae among wild-caught and captive
      vervet monkeys (Chlorocebus aethiops sabaeus) on the island of St. Kitts.
AB  - Invasive, hypermucoid Klebsiella pneumoniae causes severe abscess formation in
      humans and in certain species of nonhuman primates. We conducted a survey of
      captive and wild-caught African green monkeys, or vervets (Chlorocebus aethiops
      sabaeus), on the Caribbean island of St. Kitts to assess their carriage rate of
      Klebsiella spp. Forty percent of rectal swabs from captive monkeys were positive
      for K. pneumoniae, and 20% of wild-caught animals were positive. Two wild-caught
      monkeys (4%) were positive for K. oxytoca, and one monkey (2%) was found to be
      infected with a hypermucoid rmpA-positive K. pneumoniae strain. Genotyping of
      this strain showed that it had an indistinguishable random amplified polymorphic
      DNA fingerprint to a strain that caused fatal abscessation in several African
      green monkeys in a research colony in the USA in 2005. This is the first report
      of hypermucoid K. pneumoniae isolation from a wild population of nonhuman
      primates and represents a potential health risk to these animals, as well as to
      the humans who come in contact with them.

PMID- 20688709
TI  - Prevalence of antibodies to Toxoplasma gondii in woodchucks across an urban-rural
      gradient.
AB  - Increasing urbanization has important consequences for wildlife, including the
      potential for higher prevalence of diseases within "urban adapter" species
      exposed to spillover from domestic animals. We investigated whether prevalence of
      antibodies to Toxoplasma gondii in woodchucks (Marmota monax) was related to
      urbanization in a Midwestern landscape. We collected serum samples from adult
      woodchucks captured across an urban-rural gradient in Illinois, USA in May
      November 2007. We used an indirect fluorescent antibody test (IFAT) on the serum
      samples to detect T. gondii antibodies. Five of 35 (14.3%) sera from woodchucks
      had detectable T. gondii antibodies. Prevalence was related positively to
      urbanization. All positive samples were from individuals inhabiting areas in
      which urban land cover exceeded 70%. Urban woodchucks are likely exposed to high
      levels of T. gondii oocysts in the environment due to habitat overlap with the
      definitive hosts for the parasite, domestic and feral cats, which reach high
      densities in urban areas.

PMID- 20688710
TI  - Canada geese and the epidemiology of avian influenza viruses.
AB  - Canada geese (Branta canadensis) are numerous, highly visible, and widely
      distributed in both migratory and resident populations in North America; as a
      member of the order Anseriformes, they are often suggested as a potential
      reservoir and source for avian influenza (AI) viruses. To further examine the
      role of Canada Geese in the ecology of AI, we re-evaluated existing literature
      related to AI virus in this species and tested breeding populations of Canada
      Geese from three states (Georgia, West Virginia, and Minnesota, USA) by virus
      isolation and serology. The ability of AI virus to persist in goose feces under
      experimental conditions also was evaluated as an additional measure of the
      potential for this species to serve as an AI virus reservoir. Virus was not
      isolated from 1,668 cloacal swabs and type-specific antibody prevalence was low
      (4/335, 1.2%). Finally, under experimental conditions, AI virus persistence in
      goose feces and in water contaminated with goose feces was limited as compared to
      published estimates from duck feces and water. Our results are consistent with
      historic reports of a low prevalence of AI virus infection in this species, and
      we suggest that Canada Geese play a minor, if any, role as a reservoir for low
      pathogenic AI viruses that naturally circulate in wild bird populations.

PMID- 20688711
TI  - Muellerius capillaris dominates the lungworm community of bighorn sheep at the
      National Bison Range, Montana.
AB  - Lungworm infections are common among bighorn sheep (Ovis canadensis) in North
      America, and the predominant species reported are Protostrongylus stilesi and P.
      rushi. The only records of another lungworm species, Muellerius capillaris,
      infecting bighorns come from South Dakota, USA. At the National Bison Range
      (NBR), Montana, USA we found that across six sampling periods, 100% of wild
      bighorn sheep surveyed were passing first-stage dorsal-spined larvae (DSL) which
      appeared to be consistent with M. capillaris. By contrast, only 39% or fewer
      sheep were passing Protostrongylus larvae. Using molecular techniques, we
      positively identified the DSL from the NBR bighorns as M. capillaris. This is the
      first definitive record of M. capillaris infection in a free-ranging bighorn
      sheep population outside of South Dakota.

PMID- 20688712
TI  - Mycoplasma sturni from a California House Finch with conjunctivitis did not cause
      disease in experimentally infected House Finches.
AB  - Mycoplasma gallisepticum conjunctivitis emerged in 1994 as a disease of free
      ranging House Finches (Carpodacus mexicanus) in North America and has also been
      isolated from other songbirds with conjunctivitis. A key feature for the
      successful study of natural and experimental disease has been the apparent, very
      high correlation between characteristic eye lesions and M. gallisepticum.
      Mycoplasma sturni was originally isolated from an adult European Starling
      (Sturnus vulgaris) with bilateral conjunctivitis and has since been reported in a
      relatively small number of other avian species, but not in House Finches. We
      identified as M. sturni a mycoplasma isolate from a California House Finch with
      conjunctivitis. However, experimental infection of House Finches with the M.
      sturni isolate failed to reproduce the disease. Therefore, M. gallisepticum
      remains the primary known cause of conjunctivitis in House Finches.

PMID- 20688713
TI  - Alopecia in bats from Tabasco, Mexico.
AB  - We report alopecic syndrome (hair loss in areas of the body, including chest,
      abdomen, and back) in four frugivorous bat species (Artibeus jamaicensis,
      Artibeus lituratus, Sturnira lilium, and Sturnira ludovici) within urban and
      periurban areas of Villahermosa, Tabasco, Mexico, during 2007 and 2008. The
      overall prevalence of alopecic syndrome was 5.25% (135/2,567 bats). The highest
      prevalence was found in A. lituratus (5.6%; 62/1,105), followed by A. jamaicensis
      (5%; 3/1,462). We found a higher prevalence in the dry season, when more than 90%
      of the alopecic individuals (n=122) were captured. Higher prevalence of alopecia
      was recorded in urban areas (80% of captured alopecic bats, n=108) than in
      periurban areas (20%, n=27). Histopathologic studies revealed no evidence of
      infectious agents. The syndrome may be related to nutritional or endocrinal
      deficiencies. Spatial and seasonal aggregation in urban areas suggests that
      anthropogenic activities may interfere with nutritional processes. Further
      studies are needed to confirm the etiology of the syndrome as well as its impact
      on population dynamics. This is the first report of alopecic syndrome in sylvatic
      bats.

PMID- 20688714
TI  - Exposure to Toxoplasma gondii in Galapagos Penguins (Spheniscus mendiculus) and
      flightless cormorants (Phalacrocorax harrisi) in the Galapagos Islands, Ecuador.
AB  - Toxoplasma gondii is one of the most common protozoan parasites of humans and
      warm-blooded animals. Members of the family Felidae are the only definitive hosts
      of this parasite and, thus, important in the epidemiology of the disease.
      Previous studies on Pacific islands have found T. gondii infections in a number
      of avian species where domestic cats (Felis catus) have been introduced. Little
      is known about T. gondii in the Galapagos Islands, although introduced domestic
      cats in the archipelago are known to be T. gondii antibody-positive. In this
      study, we quantified prevalence of antibody to T. gondii in two threatened avian
      marine species, Galapagos Penguins (Spheniscus mendiculus) and Flightless
      Cormorants (Phalacrocorax harrisi), and tested the hypothesis that this parasite
      is more prevalent on Isabela Island (with cats) than on Fernandina Island
      (without cats). Overall, antibody prevalence was 2.3% in both Galapagos Penguins
      and Flightless Cormorants from samples collected during 2003-2005, and in 2008.
      In Galapagos Penguins (n=298), a significantly higher antibody prevalence was
      found in penguins on Fernandina Island (free of cats) than on Isabela Island
      (with cats; Fisher's exact test; P=0.02). In Flightless Cormorants (n=258), there
      was a higher antibody prevalence in cormorants living on Isabela than on
      Fernandina, although this difference was not statistically significant (Fisher's;
      P=0.19). This study is the first to show exposure to T. gondii in endemic avian
      species in the Galapagos Islands, providing evidence for disease-related risks
      associated with the feral cat population in the archipelago. We provide possible
      explanations for these findings and recommendations for future studies towards a
      better understanding of the epidemiology of T. gondii in the Galapagos Islands.

PMID- 20688715
TI  - Ovarian interstitial cell tumor in a South American sea lion (Otaria flavescens).
AB  - A case of an ovarian tumor is reported in an 8-yr-old South American sea lion
      (Otaria flavescens) kept in a marine park in Malta (35.57 degrees N, 14.25
      degrees E). The neoplasm was a solid mass of dense sheets and nests of round to
      polyhedral, irregularly shaped cells with abundant, finely vacuolated cytoplasm.
      The nuclei were uniformly small and round to oval. The supporting stroma
      contained thecal cells. The tumor cells were positive for positive inhibin and
      vimentin and focally positive for cytokeratin by immunohistochemistry. The
      neoplasm was diagnosed as an ovarian sex cord-stromal tumor, specifically an
      interstitial cell tumor.

PMID- 20688716
TI  - Molecular and serologic detection of Ehrlichia spp. in endangered Brazilian wild
      captive felids.
AB  - Ehrlichiosis, an emergent tick-borne disease that affects both humans and
      animals, may represent a threat to the survival and preservation of wild felids
      in Brazil. There are few studies of ehrlichiosis in wild felids in Brazil, but
      Ehrlichia spp. are present in domestic cats. Antibodies to Ehrlichia canis have
      been reported in a puma (Puma concolor). In this study we assessed the presence
      of these hemoparasites in the blood of Brazilian wild captive felids. Of the 72
      animals tested, 5 (7%) were seropositive for the E. canis antigen, and 11 (15%)
      were positive for E. canis DNA sequences. We also performed sequence alignment to
      establish the identity of the parasite species infecting these animals using 16S
      rRNA and omp-1 genes. Sequences based on 16S rRNA were similar to those found in
      dogs and cats from Thailand, Brazil, China, and Taiwan and with E. canis obtained
      from a single individual (human) in Venezuela. Ehrlichia sp. sequence from
      sampled felines based on omp-1 gene was similar to the p28 and p30 multigene
      family of E. canis. To our knowledge, this is the first study of molecular
      detection of Ehrlichia sp. in Brazilian wild feline species.

PMID- 20688717
TI  - Response of captive skunks to microencapsulated tetracycline.
AB  - A captive striped skunk (Mephitis mephitis) study was conducted between February
      and June 2004 at the United States Department of Agriculture, Animal and Plant
      Health Inspection Service, Wildlife Services National Wildlife Research Center,
      Fort Collins, Colorado, USA. The main objective was to determine the percentage
      of adult striped skunks that were marked after consuming placebo oral rabies
      vaccine (ORV) baits containing 100 mg of an experimental microencapsulated
      (coated microparticle) tetracycline hydrochloride biomarker. Biomarkers were
      identified in the canine teeth and mandibles of five of five skunks that consumed
      an ORV bait. A second objective was to determine if the microencapsulated
      tetracycline was resistant to photochemical conversion from tetracycline to
      epitetracycline. After 15 days of exposure, conversion from tetracycline to
      epitetracycline concentration in the microencapsulated product (mean 1.9%
      conversion, SD=1.24) was significantly less (P=0.006) than the pure-grade
      tetracycline powder (mean 7.5% conversion, SD=1.37). Results support the use of
      microencapsulated tetracycline hydrochloride as a biomarker in circumstances
      where the use of conventional powdered tetracycline hydrochloride is not feasible
      due to ORV bait design constraints.

PMID- 20688718
TI  - Select tissue mineral concentrations and chronic wasting disease status in mule
      deer from North-central Colorado.
AB  - Trace mineral imbalances have been suggested as having a causative or
      contributory role in chronic wasting disease (CWD), a prion disease of several
      North American cervid species. To begin exploring relationships between tissue
      mineral concentrations and CWD in natural systems, we measured liver tissue
      concentrations of copper, manganese, and molybdenum in samples from 447
      apparently healthy, adult (> or = 2 yr old) mule deer (Odocoileus hemionus)
      culled or vehicle killed from free-ranging populations in north-central Colorado,
      United States, where CWD occurs naturally; we also measured copper concentrations
      in brain-stem (medulla oblongata at the obex) tissue from 181 of these deer.
      Analyses revealed a wide range of concentrations of all three minerals among
      sampled deer (copper: 5.6-331 ppm in liver, 1.5-31.9 ppm in obex; manganese: 0.1
      21.4 ppm in liver; molybdenum: 0.5-4.0 ppm in liver). Bayesian multiple
      regression analysis revealed a negative association between obex copper (-0.097;
      95% credible interval -0.192 to -0.006) and the probability of sampled deer also
      being infected with CWD, as well as a positive association between liver
      manganese (0.158; 95% credible interval 0.066 to 0.253) and probability of
      infection. We could not discern whether the tendencies toward lower brain-stem
      copper concentrations or higher systemic manganese concentrations in infected
      deer preceded prion infection or rather were the result of infection and its
      subsequent effects, although the distribution of trace mineral concentrations in
      infected deer seemed more suggestive of the latter.

PMID- 20688719
TI  - Mercury poisoning in a free-living northern river otter (Lontra canadensis).
AB  - A moribund 5-year-old female northern river otter (Lontra canadensis) was found
      on the bank of a river known to be extensively contaminated with mercury. It
      exhibited severe ataxia and scleral injection, made no attempt to flee, and died
      shortly thereafter of drowning. Tissue mercury levels were among the highest ever
      reported for a free-living terrestrial mammal: kidney, 353 microg/g; liver, 221
      microg/g; muscle, 121 microg/g; brain (three replicates from cerebellum), 142,
      151, 151 microg/g (all dry weights); and fur, 183 ug/g (fresh weight).
      Histopathologic findings including severe, diffuse, chronic glomerulosclerosis
      and moderate interstitial fibrosis were the presumptive cause of clinical signs
      and death. This is one of a few reports to document the death of a free-living
      mammal from presumed mercury poisoning.

PMID- 20688720
TI  - Antibodies to type A influenza virus in wild waterbirds from Argentina.
AB  - Limited information exists on avian influenza (AI) virus infection in South
      American wild birds. As part of a national surveillance program in Argentina,
      indigenous waterbirds were screened for antibodies to AI virus. From November
      2006 to July 2007, serum samples from 540 waterbirds of 12 species were tested
      for type-specific antibodies to AI virus with the use of a commercially available
      blocking enzyme-linked immunosorbent assay (bELISA) and the agar-gel
      immunodiffusion (AGID) test. Thirty-three percent (176/540) of serum samples were
      positive with the bELISA and 12% (64/540) were positive with the AGID test. The
      bELISA detected antibodies to AI virus in eight of the 12 species, and the AGID
      detected positives in only five species. These results provide insight into AI
      virus circulation in Argentinean waterbirds and preliminary data to guide further
      surveillance efforts.

PMID- 20688721
TI  - Pathology and epidemiology of phocid herpesvirus-1 in wild and rehabilitating
      harbor seals (Phoca vitulina richardsi) in the northeastern Pacific.
AB  - Phocid herpesvirus-1 (PhHV-1, subfamily Alphaherpesvirinae) was isolated from
      harbor seals (Phoca vitulina vitulina) in the Netherlands in 1985, and was
      subsequently identified in Pacific harbor seals (Phoca vitulina richardsi) from
      California, USA in the 1990s. PhHV-1-associated pathology was first recognized in
      harbor seal carcasses submitted to a veterinary diagnostic laboratory in
      Abbotsford, British Columbia, Canada in 2000, and 63 cases were identified by
      2008. A review of these cases indicated that PhHV-1-associated disease is
      widespread in harbor seals in the wild and within rehabilitation facilities in
      the coastal northeastern Pacific (including British Columbia, Canada, and
      Washington, USA). Morbidity and mortality occurred primarily in neonatal and
      weanling seal pups, and was due to PhHV-1 alone, or in combination with other
      disease processes. All cases occurred between July and October, corresponding to
      the pupping and weaning seasons in this area. Although previous publications have
      described the prevalence of antibody to PhHV-1 in harbor seals from British
      Columbia, Canada and Washington, USA this is the first study to focus on the
      epidemiology and pathology of the virus in this region.

PMID- 20688722
TI  - Lung worm (Metastrongylus elongatus) infection in wild boars (Sus scrofa) of the
      demilitarized zone, Korea.

PMID- 20688724
TI  - Evidence for the major contribution of evaporation to tear film thinning between
      blinks.
AB  - PURPOSE: To determine the contribution of evaporation to the thinning of the
      precorneal tear film between blinks. METHODS: The rate of tear film thinning
      after a blink was measured using spectral interferometry from the right eyes of
      37 subjects. Data were obtained under two different conditions: free air and air
      tight goggles. RESULTS: The mean (+/-SD) tear film thinning rates for subjects
      was 3.22 +/- 4.27 MUm/min in free air and -0.16 +/- 1.78 MUm/min (i.e., a slight
      but not significant thickening) for the same subjects wearing air-tight goggles;
      this reduction in thinning rates was significant (P < 0.0001). CONCLUSIONS: The
      large reduction in thinning rate caused by wearing goggles indicates that
      evaporation is the major cause of thinning between blinks. The mean thinning rate
      in free air is greater than reported evaporation rates; it is argued that the
      preocular chambers used in evaporimeters restrict movement of air over the tear
      film and reduce evaporation compared to our free air condition.

PMID- 20688725
TI  - Effects of acutely elevated hydrostatic pressure in a rat ex vivo retinal
      preparation.
AB  - PURPOSE: A new experimental glaucoma model was developed by using an ex vivo rat
      retinal preparation to examine the effects of elevated hydrostatic pressure on
      retinal morphology and glutamine synthetase (GS) activity. METHODS: Ex vivo rat
      retinas were exposed to elevated hydrostatic pressure for 24 hours in the
      presence of glutamate or glutamate receptor antagonists and examined
      histologically. GS activity was assessed by colorimetric assay. RESULTS: Pressure
      elevation induced axonal swelling in the nerve fiber layer. Axonal swelling was
      prevented by a combination of non-N-methyl-d-aspartate (non-NMDA) receptor
      antagonist and an NMDA receptor antagonist, indicating that the damage results
      from activation of both types of glutamate receptor. When glial function was
      preserved, the typical changes induced by glutamate consisted of reversible
      Muller cell swelling resulting from excessive glial glutamate uptake. The
      irreversible Muller cell swelling in hyperbaric conditions may indicate that
      pressure disrupts glutamate metabolism. Indeed, elevated pressure inhibited GS
      activity. In addition, glutamate exposure after termination of pressure exposure
      exhibited apparent Muller cell swelling. CONCLUSIONS: These results suggest that
      the neural degeneration observed during pressure elevation is caused by impaired
      glial glutamate metabolism after uptake.

PMID- 20688726
TI  - Neovascularization, enhanced inflammatory response, and age-related cone
      dystrophy in the Nrl-/-Grk1-/- mouse retina.
AB  - PURPOSE: The effects of aging and light exposure on cone photoreceptor survival
      were compared between mouse retinas of neural retina leucine zipper knockout
      (Nrl(-/-)) mice and double-knockout mice lacking G-protein-coupled receptor
      kinase 1 (Nrl(-/-)Grk1(-/-)). METHODS: Mice were reared in total darkness,
      ambient cyclic light, or constant light, and their retinas were evaluated from 1
      to 9 months of age using immunohistochemistry, electroretinography, and
      fluorescein angiography. Retinal gene expression and statistically significant
      probe sets were categorized using analysis software. Select gene expression
      changes were confirmed with quantitative RT-PCR. RESULTS: In contrast to retinas
      from Nrl(-/-), those from Nrl(-/-)Grk1(-/-) exhibit a progressive loss of the
      outer nuclear layer, retinal physiology deficits, and a higher rate of
      degeneration with increasing age that is independent of environmental light
      exposure. Changes in retinal neovascularization occur in the Nrl(-/-)Grk1(-/-) at
      1 month, before the onset of significant cone functional deficits. Microarray
      analyses demonstrate statistically significant changes in transcript levels of
      more than 400 genes, of which the oncostatin M signaling pathway and the
      inflammatory disease response network were identified. CONCLUSIONS: These data
      demonstrate that the loss of functional Grk1 on the enhanced S-cone Nrl(-/-)
      background exacerbates age-related cone dystrophy in a light-independent manner,
      mediated partly through the inflammatory response pathway and neovascularization.
      According to these findings, Grk1 helps to maintain a healthy cone environment,
      and the Nrl(-/-)Grk1(-/-) mouse allows examination of the alternative roles of
      Grk1 in cone photoreceptor homeostasis.

PMID- 20688727
TI  - Decay accelerating factor (CD55)-mediated attenuation of complement: therapeutic
      implications for age-related macular degeneration.
AB  - PURPOSE: Sequence variations in complement proteins are associated with age
      related macular degeneration (AMD). The terminal pathway of complement results in
      the formation of the membrane attack complex (MAC) on the cell surface, resulting
      in their lysis. MAC has been documented on the retinal pigment epithelium (RPE),
      choroidal blood vessels, and drusen of AMD eyes. Here the investigators test the
      hypothesis that increasing the expression of decay accelerating factor (CD55) on
      RPE cells may result in reduced MAC-mediated damage. METHODS: The investigators
      constructed a recombinant adenovirus expressing human CD55 (AdCAGCD55). Mouse
      hepatocytes were infected with AdCAGCD55 or negative controls and subsequently
      incubated with normal human serum (NHS). Cell lysis and MAC formation were
      measured by FACS and immunocytochemistry, respectively. Adult mice were injected
      in the subretinal space with either AdCAGCD55 or controls; after 1 week of CD55
      transgene expression, the eyecups were excised, challenged with NHS, and
      quantified for human MAC formation. RESULTS: Control-infected or uninfected mouse
      hepatocytes lyse at a rate of 93% and 94%, respectively. AdCAGCD55- infected
      mouse hepatocytes lyse at a rate of 29%. Lysis was confirmed to occur in the
      presence of MAC, which was reduced by 67% when cells were infected by AdCAGCD55.
      Mice injected in the subretinal space with AdCAGCD55 exhibited a 55.7% reduction
      in MAC formation on the RPE relative to controls. CONCLUSIONS: Adenovirus
      mediated delivery of hCD55 to murine RPE confers protection against human
      complement. The investigators propose that the expression of hCD55 on RPE cells
      warrants investigation as a potential therapy for AMD.

PMID- 20688728
TI  - Outcomes of cataract surgery in urban southern China: the Liwan Eye Study.
AB  - PURPOSE: The outcomes of cataract surgery have been well reported in rural China;
      however, the situation in the urban population remains unclear. This study
      assessed the outcomes of cataract surgery in urban southern China. METHODS: Data
      were gathered from the Liwan Eye Study, a population-based, cross-sectional study
      conducted in people aged 50 years or more in the Liwan District of Guangzhou.
      Presenting and best corrected visual acuity and a detailed eye examination were
      performed. For all aphakic and pseudophakic participants identified, information
      on the date, setting, type, and complications of cataract surgery were recorded.
      RESULTS: Of the 1405 participants, 62 people (90 eyes) had undergone cataract
      surgery. Of those, 54.4% underwent the phacoemulsification (Phaco) technique,
      33.3% extracapsular cataract extraction (ECCE) with intraocular lens (IOL)
      implantation, and 11.1% ECCE without IOL; 1 patient had intracapsular cataract
      extraction (ICCE). Presenting visual acuity (PVA) was >6/18 in 56 (62.2%) eyes,
      <6/18 to >6/60 in 20 (22.2%) eyes, <6/60 to >3/60 in 3 (3.3%) eyes, and <3/60 in
      11(12.3%) eyes. Of the 34 eyes with PVA less than 6/18, the principal causes were
      26.5% retinal abnormalities, 20.6% glaucoma, 35.3% uncorrected aphakia or
      refractive error, and 14.5% posterior capsule opacification (PCO). CONCLUSIONS:
      ECCE or Phaco with IOL are the major surgical techniques used in urban southern
      China. More than half of the eyes with poor outcomes due to uncorrected aphakia,
      refractive error, or PCO are potentially treatable. This result suggests a
      pressing need for improved surgical training and postoperative care.

PMID- 20688729
TI  - The effect of bifocal add on accommodative lag in myopic children with high
      accommodative lag.
AB  - PURPOSE: To determine the effect of a bifocal add and manifest correction on
      accommodative lag in myopic children with high accommodative lag, who have been
      reported to have the greatest reduction in myopia progression with progressive
      addition lenses (PALs). METHODS: Monocular accommodative lag to a 4-D Badal
      stimulus was measured on two occasions 6 months apart in 83 children (mean +/- SD
      age, 9.9 +/- 1.3 years) with high lag randomized to wearing single-vision lenses
      (SVLs) or PALs. Accommodative lag was measured with the following corrections:
      habitual, manifest, manifest with +2.00-D add, and habitual with +2.00-D add (6
      month visit only). RESULTS: At baseline, accommodative lag was higher (1.72 +/-
      0.37 D; mean +/- SD) when measured with manifest correction than with habitual
      correction (1.51 +/- 0.50; P < 0.05). This higher lag with manifest correction
      correlated with a larger amount of habitual undercorrection at baseline (r = 
      0.29, P = 0.009). A +2.00-D add over the manifest correction reduced lag by 0.45
      +/- 0.34 D at baseline and 0.33 +/- 0.38 D at the 6-month visit. Lag results at 6
      months were not different between PAL and SVL wearers (P = 0.92). CONCLUSIONS: A
      +2.00-D bifocal add did not eliminate accommodative lag and reduced lag by less
      than 25% of the bifocal power, indicating that children mainly responded to a
      bifocal by decreasing accommodation. If myopic progression is substantial,
      measuring lag with full correction can overestimate the hyperopic retinal blur
      that a child most recently experienced. (ClinicalTrials.gov number,
      NCT00335049.).

PMID- 20688730
TI  - Intersubject variability of foveal cone photoreceptor density in relation to eye
      length.
AB  - PURPOSE: Adaptive optics scanning laser ophthalmoscopy (AOSLO) under optimized
      wavefront correction allows for routine imaging of foveal cone photoreceptors.
      The intersubject variability of foveal cone density was measured and its relation
      to eye length evaluated. METHODS: AOSLO was used to image 18 healthy eyes with
      axial lengths from 22.86 to 28.31 mm. Ocular biometry and an eye model were used
      to estimate the retinal magnification factor. Individual cones in the AOSLO
      images were labeled, and the locations were used to generate topographic maps
      representing the spatial distribution of density. Representative retinal
      (cones/mm(2)) and angular (cones/deg(2)) cone densities at specific
      eccentricities were calculated from these maps. RESULTS: The entire foveal cone
      mosaic was resolved in four eyes, whereas the cones within 0.03 mm eccentricity
      remained unresolved in most eyes. The preferred retinal locus deviated
      significantly (P < 0.001) from the point of peak cone density for all except one
      individual. A significant decrease in retinal density (P < 0.05) with increasing
      axial length was observed at 0.30 mm eccentricity but not closer. Longer, more
      myopic eyes generally had higher angular density near the foveal center than the
      shorter eyes, but by 1 degrees , this difference was nullified by retinal
      expansion, and so angular densities across all eyes were similar. CONCLUSIONS:
      The AOSLO can resolve the smallest foveal cones in certain eyes. Although myopia
      causes retinal stretching in the fovea, its effect within the foveola is
      confounded by factors other than cone density that have high levels of
      intersubject variability.

PMID- 20688731
TI  - 7.1 T MRI to assess the anterior segment of the eye.
AB  - PURPOSE: Visualization of the anterior segment and biometric evaluation of the
      entire crystalline lens pose significant challenges for imaging techniques
      because of tissue-induced distortion artifacts. The present study was conducted
      to demonstrate the advantages of high-resolution magnetic resonance imaging
      (micro-MRI) for visualizing the anterior segment. METHODS: High-resolution MR
      ocular images were acquired on an ultra-high-field MR unit using a two-channel
      coil with four coil elements and T(2)-weighted turbo spin echo sequences ex vivo
      in pig, rabbit, monkey, and human donor eyes and in vivo in rabbits. Tissue
      heating, reproducibility, and signal-to-noise ratio were investigated in vivo.
      Monkey eye lens thickness (LT) was also measured using A-scan ultrasonography
      (US). RESULTS: Anterior segment details of phakic eyes were obtained ex vivo
      (pig, rabbit, monkey, and human donor eyes) with pixel matrix size 512 * 512 (in
      plane resolution 80 * 80 MUm) and in vivo (rabbit eyes) with pixel matrix size
      320 * 320 (in-plane resolution 125 * 125 MUm). Complete quantification of lens
      dimensions as they correlate with the sulcus-sulcus and angle-angle plane can be
      performed. In LT determinations in monkey eyes, no significant difference was
      detected between micro-MRI and A-scan US (P > 0.05, Mann-Whitney U test).
      Biometric analysis of one pseudophakic monkey eye confirmed the absence of
      relevant distortion artifacts. CONCLUSIONS: Micro-MRI allows ex vivo and in vivo
      visualization and quantification of the spatial arrangement of the anterior eye
      segment. Imaging of the retroiridian region, including the entire crystalline
      lens, overcomes a number of major limitations in the quantitative evaluation of
      the anterior segment.

PMID- 20688732
TI  - Microglial activation in the visual pathway in experimental glaucoma:
      spatiotemporal characterization and correlation with axonal injury.
AB  - PURPOSE: Glia are the main cellular CNS elements initiating defense mechanisms
      against destructive influences and promoting regenerative processes. The aim of
      the current work was to characterize the microglial response within the visual
      pathway in a rat model of experimental glaucoma and to correlate the microglial
      response with the severity of axonal degeneration. METHODS: Experimental glaucoma
      was induced in each right eye of adult Sprague-Dawley rats by translimbal laser
      photocoagulation of the trabecular meshwork. Rats were subsequently killed at
      various times from 3 days to 6 weeks. Tissue sections were obtained from globes,
      optic nerves, chiasmata, and optic tracts for immunohistochemistry and toluidine
      blue staining. RESULTS: This model of experimental glaucoma led to a marked
      activation of microglia in the retina, optic nerve, and tract. Indeed, microglial
      activity remained elevated, even after intraocular pressure returned to basal
      levels. It is postulated that this process accompanies ongoing axonal
      degeneration. The degree of activation in the optic nerve correlated with axonal
      damage. Activation was characterized by increased density and morphologic
      changes. Both major histocompatibility complex (MHC) class I and MHC class II
      surface proteins were persistently upregulated in optic nerves and localized to
      microglial cells; however, this did not correlate with any significant T-cell
      infiltration. Interestingly, MHC class II expression was not detected in the
      retina. CONCLUSIONS: The present data may have implications for the study of the
      pathology associated with the visual pathway in diseases such as glaucoma.

PMID- 20688733
TI  - Intravitreal injection of exendin-4 analogue protects retinal cells in early
      diabetic rats.
AB  - PURPOSE: To evaluate the protective effect of intravitreal injection of exendin-4
      analogue (E4a) in early diabetic retinopathy (DR) and to explore its possible
      mechanism. METHODS: Forty Sprague-Dawley rats were divided into three groups:
      normal (N), diabetic (D), and E4a-treated diabetic rats (E4a). Diabetes was
      induced by streptozotocin. Rats in the E4a group were treated with E4a (0.1
      MUg/2MUL/eye), whereas the N and D groups were treated with the equivalent volume
      of normal saline. Electroretinography was performed at 1 month and 3 months after
      diabetes onset. Thicknesses and cell counts in each layer of the retina were
      evaluated. The concentration of glutamate was measured by high-performance liquid
      chromatography (HPLC). Expressions of glucagon-like peptide-1 receptor (GLP-1R)
      and GLAST (excitatory amino acid transporter) were detected at mRNA and protein
      levels and verified by immunohistochemistry in vitro and in vivo. The rMc-1 cells
      were cultured under high-glucose medium (25 mM), which mimicked diabetic
      conditions. Effects of E4a (10 MUg/mL) were also tested in the rMc-1 culture
      system. RESULTS: E4a prevented the reduction in b-wave amplitude and oscillatory
      potential amplitude caused by diabetes. It also prevented the cell loss of outer
      nuclear layer and inner nuclear layer; the thickness and cell count in the outer
      nuclear layer were decreased in 1-month diabetic rats. The concentration of
      glutamate in the retina was higher in diabetic rats and was significantly reduced
      in the E4a-treated group. Consistent with such changes, retinal GLP-1R and GLAST
      expression were reduced in the diabetic retina but upregulated in E4a-treated
      rats. No improvement was found in the retina in both functional and morphologic
      parameters 3 months after treatment. CONCLUSIONS: Intravitreal administration of
      E4a can prevent the retina, functionally and morphologically, from the insults of
      diabetes in rats. GLP-1R and GLAST were proved to exist in the rat retina, and
      their lowered expressions in the diabetic retina might be related to retinal
      damage by increasing the retinal glutamate. E4a might protect the retina by
      reducing the glutamate level through upregulating GLP-1R and GLAST, as observed
      in retinal Muller cells in this study, but this protective effect was transient.
      Thus, this could be a potential approach for the treatment of DR.

PMID- 20688734
TI  - Optical coherence tomography and autofluorescence findings in areas with
      geographic atrophy due to age-related macular degeneration.
AB  - PURPOSE: To analyze outer retinal changes within the atrophic lesion in patients
      with geographic atrophy (GA) secondary to age-related macular degeneration.
      METHODS: Twenty-one simultaneously obtained fundus autofluorescence (FAF,
      excitation, 488 nm; emission, 500-700 nm) and spectral-domain optical coherence
      tomography (SD-OCT) scans (Spectralis HRA+OCT; Heidelberg Engineering,
      Heidelberg, Germany) of 21 GA patients (mean age, 75.1 +/- 7.4 years) were
      included and separately exported. Two readers independently graded the following
      parameters: width of the atrophic lesion on the FAF image at the site where the
      SD-OCT scan had been placed; and on the SD-OCT image, widths of the linear
      disruption of the outer nuclear layer, the external limiting membrane, and the
      inner and outer segments of the photoreceptor layer (IPRL) and width of the
      disruption of choroidal signal enhancement. Results. The mean width of the
      atrophic lesion by FAF imaging was 2.83 mm (95% confidence interval, 2.37-3.29).
      The linear disruption of choroidal hyperreflectivity showed the closest agreement
      with 2.83 mm (2.37-3.28), whereas the linear width of disrupted IPRL was larger
      (3.10 mm; 2.65-3.55). Overall, the width of the atrophic lesion correlated
      significantly with all five SD-OCT parameters (P < 0.0001, r = 0.96-0.99).
      CONCLUSIONS: These findings demonstrate that the atrophic lesions identified with
      FAF represent irreversible underlying outer retinal damage. The observation that
      the width of the atrophic lesion identified with FAF, although significantly
      correlated but not identical with the width of disruption within the cellular
      layers of the retina, is consistent with the dynamic nature of the disease.
      (ClinicalTrials.gov numbers, NCT00393692, NCT00599846.).

PMID- 20688735
TI  - Retrobulbar blood flow velocities in open angle glaucoma and their association
      with mean arterial blood pressure.
AB  - PURPOSE: A number of previous studies have shown that blood velocities in
      retrobulbar arteries, as assessed with color Doppler imaging (CDI), are reduced
      in primary open angle glaucoma (POAG) patients, indicative of reduced blood flow
      to the eye. In the present study, the authors hypothesized that patients with
      POAG show an abnormal association between retrobulbar blood flow velocities as
      assessed with CDI and blood pressure, indicative of vascular dysregulation.
      METHODS: A total of 252 POAG patients and 198 healthy age-matched control
      subjects were included. Mean flow velocity (MFV) in the ophthalmic artery (OA),
      posterior ciliary artery (PCA), and central retinal artery (CRA) were measured
      with CDI. Mean arterial blood pressure was measured noninvasively using automated
      oscillometry, and intraocular pressure was measured using Goldmann applanation
      tonometry. RESULTS: Intraocular pressure was increased in POAG patients compared
      with healthy controls (P < 0.01). Mean arterial blood pressure was not different
      between groups. All blood flow velocities were significantly reduced in POAG
      patients compared with healthy control subjects (P < 0.01 each). The correlation
      between MFV and mean arterial blood pressure in the CRA was stronger in POAG
      subjects than in healthy control subjects. CONCLUSIONS: These data indicate that
      blood flow velocities in retrobulbar vessels are reduced in POAG patients
      compared with healthy control subjects. In addition, an abnormal correlation
      between blood velocities and mean arterial blood pressure was found in POAG. This
      suggests vascular dysregulation and supports the concept that reduced ocular
      blood flow in glaucoma is not solely a consequence of the disease.

PMID- 20688736
TI  - Novel discovery of LYVE-1 expression in the hyaloid vascular system.
AB  - PURPOSE: The hyaloid vascular system (HVS) is a transient network nourishing
      developing eyes and has been widely used as a natural model to study blood vessel
      regression. Failure of its regression in humans leads to several blinding
      diseases. Lymphatic vessel endothelial hyaluronic acid receptor (LYVE-1) is a
      recently defined lymphatic marker that is also expressed by a subpopulation of
      macrophages. To date, there is no report on its expression in the HVS. This study
      was conducted to investigate whether LYVE-1 is expressed in the HVS and how it is
      associated with the vascular structure and macrophage phenotype. METHODS: Normal
      C57BL/6 mouse eyeballs were sampled from embryonic day (E) 10.5 to postnatal (P)
      and adult stages for immunofluorescent microscopic studies with antibodies
      against LYVE-1, CD31 (panendothelial cell marker), and F4/80 (macrophage marker).
      Additionally, Angiopoietin-2 (Ang-2) knockout mice with abnormally persistent HVS
      were examined. RESULTS: The LYVE-1 expression was detected on normal HVS between
      E12.5 and P14. The LYVE-1(+) cells were F4/80(+) but CD31(-), indicating a
      macrophage lineage. Additionally, LYVE-1(+) cells bud on CD31(+) vessels and
      constitute an integral part of the network in both normal developing and Ang-2
      knockout mice. CONCLUSIONS: This study provides the first evidence that the HVS
      contains a LYVE-1(+) cellular component in both physiological and pathologic
      conditions. This novel finding not only provides a new concept in defining the
      embryogenesis and pathogenesis of the HVS, it also leads to a completely natural
      model in which to study the functions of the LYVE-1 pathway, an important topic
      for lymphatic research as well.

PMID- 20688737
TI  - Joint effect of cigarette smoking and CFH and LOC387715/HTRA1 polymorphisms on
      polypoidal choroidal vasculopathy.
AB  - PURPOSE: To investigate whether the major genetic and environmental risk factors
      of age-related macular degeneration (AMD)-CFH Y402H and LOC387715 A69S and
      cigarette smoking-are also associated with polypoidal choroidal vasculopathy
      (PCV) and whether the associations of CFH Y402H and LOC387715 A69S with PCV are
      modified by smoking. METHODS: Three hundred seventy-five Japanese patients with
      PCV and 847 Japanese who served as population-based control subjects, all >=55
      years of age, were studied. CFH Y402H (rs1061170) and LOC387715 A69S (rs10490924)
      were genotyped with a single-nucleotide polymorphism (SNP) assay. An
      unconditional logistic regression model was used to analyze the association
      between age, sex, smoking status, CFH Y402H, LOC387715 A69S, and PCV. The synergy
      index (SI) was measured to assess gene-smoking and gene-gene interaction as a
      departure from additivity. RESULTS: CFH Y402H, LOC3387715 A69S, and cigarette
      smoking status were all significantly associated with PCV; for CFH Y402H, the
      adjusted odds ratio (OR) for the number of copies of the allele was 1.63 (95%
      confidence interval [CI], 1.12-2.36; P < 0.05); for LOC387715 A69S, the adjusted
      OR was 2.26 (95% CI, 1.83-2.78; P < 0.0001); and for smoking status (ever versus
      never smoked), the adjusted OR was 1.45 (95% CI, 1.00-2.10; P < 0.05). The joint
      effect of CFH Y402H and smoking was significantly greater than the additive
      scale, with an SI of 2.41 (95% CI, 1.14-5.10). CONCLUSIONS: CFH Y402H and
      LOC387715 A69S are both significantly associated with PCV. Cigarette smoking is
      an environmental risk factor for PCV. The findings suggest interactions between
      CFH 402H and cigarette smoking in PCV.

PMID- 20688738
TI  - Activated protein C rescues the retina from ischemia-induced cell death.
AB  - PURPOSE: Ischemia causes severe and persistent visual loss in many eye diseases,
      including central retinal vein occlusion (CRVO) and diabetic retinopathy.
      Activated protein C (APC) has been demonstrated to reduce the cell death
      associated with ischemia in the brain and kidney. This study was performed to
      examine the ability of APC to rescue hypoxia-induced retinal cell death in vitro
      and in vivo. METHODS: Retinal pigment epithelium (RPE) and photoreceptor cells
      were placed in either a normoxic or a hypoxic chamber. Immediately before they
      were subjected to ischemia, the cultures were treated with APC (3-240 MUg/mL).
      Incubation was followed by an MTT assay to determine the number of viable cells.
      The activity of caspase-3, -8, and -9 in RPE cells was also analyzed. Various
      concentrations of APC were intravitreally injected in a rat CRVO model, followed
      by TUNEL staining to detect the in vivo effects of APC. RESULTS: Lower
      concentrations of APC (0.3-30 MUg/mL) showed a cell-protective effect against
      hypoxia in vitro, whereas higher concentrations (>=120 MUg/mL) demonstrated
      cytotoxicity in both RPE and photoreceptor cells. Caspase-3, -8, and -9 were
      activated when the cells were exposed to hypoxia, but this activation was
      significantly inhibited by APC. Experimental CRVO-induced retinal cell apoptosis
      was reduced dramatically by intravitreal injection of APC. CONCLUSIONS: APC can
      reduce ischemia-induced cytotoxicity both in vitro and in vivo via blocking the
      activation of caspase-3, -8, and -9. APC may be a promising candidate for
      protecting the retina from ischemia.

PMID- 20688739
TI  - Genomic identification of significant targets in ciliochoroidal melanoma.
AB  - PURPOSE: To identify genomic targets for ciliochoroidal melanoma diagnosis,
      prognosis, and therapy. METHODS: Fifty-eight ciliochoroidal melanomas were
      analyzed by high-resolution, genome-wide, single nucleotide polymorphism (SNP)
      mapping arrays. The 58 SNP arrays were compared to 48 HapMap normals representing
      both sexes and assessed with a systematic statistical method, Genomic
      Identification of Significant Targets in Cancer (GISTIC), to identify significant
      ciliochoroidal chromosomal abnormalities including chromosome-arm-sized as well
      as focal events of amplification and deletion. The 58 SNP arrays were also
      analyzed to assess copy number. RESULTS: The 58 ciliochoroidal melanomas analyzed
      by GISTIC showed large regions of chromosome amplification on 6p and 8q in
      addition to focal amplification peaks on 1q31.3, 4p16.2, 9p23, and 9q33.1. The
      melanomas also showed large regions of deletion on 1p and all of 3, 6q, 8p, and
      16q, as well as focal deletion peaks on 2p12, 2q14.3, 4q26, 5q21.1, 7q21.11,
      8p21.3, 9p21.1, 13q21.31, 13q31.3, and 16q23.3. For each large region and focal
      peak, the statistical significance was computed, and known genes were specified.
      CONCLUSIONS: High-resolution analysis of ciliochoroidal melanoma cytogenetic
      aberration patterns supports the utility of systematic characterization of the
      cancer genome by corroborating known melanoma-related genomic aberrations and
      identifying additional melanoma-related genomic abnormalities that can be used to
      identify potential targets for diagnosis, prognosis and therapy.

PMID- 20688740
TI  - Long-term evaluation of refractive status and optical components in eyes of
      children born prematurely.
AB  - PURPOSE: To evaluate the refractive status and optical components in school age
      children born prematurely and to examine the risk factors associated with
      refractive errors. METHODS: The participants were a cohort of children aged 7 to
      9 years with gestational age less than 35 weeks or birth weight less than 1500 g.
      The participants' neonatal histories were reviewed; their refractive status and
      optical components were measured. The study results were compared with the
      results of age-matched children from a national survey. RESULTS: Of the 108
      children studied, 48 (44%) had retinopathy of prematurity (ROP); 29 (27%) had ROP
      >= stage 3. Compared with the control subjects, the study cases showed higher
      prevalence of myopia (48% vs. 29%), hyperopia (23% vs. 15%), and astigmatism (73%
      vs. 41%). Common ocular features included shallow anterior chamber depth (ACD),
      thick lenses, and steep corneal curvature. The hyperopic cases had the shortest
      axial length (AL), whereas the myopia cases had significantly shallower ACD and
      greater LT. Those with a history of ROP had more prominent changes in the
      anterior segment. Generalized estimating equations showed that refractive errors
      could be predicted by a combination of optical components. CONCLUSIONS: In
      children born prematurely, the development of myopia is mainly influenced by
      anterior segment components, whereas hyperopia is mainly attributable to short
      AL. Astigmatism is primarily cornea-related. A combination of various optical
      components results in complicated refractive outcomes. The presence of ROP may be
      associated with significantly shorter ACD, thicker lens, and higher myopia and
      astigmatism. (ClinicalTrials.gov number, NCT01045616.).

PMID- 20688741
TI  - Tracking longitudinal retinal changes in experimental ocular hypertension using
      the cSLO and spectral domain-OCT.
AB  - PURPOSE: Involvement of the outer retina is controversial in glaucoma. The aim of
      this study was to test, first, whether the outer retina is affected in
      experimental ocular hypertension (OHT) and, second, whether whole retinal
      thickness can be used as a surrogate marker of glaucomatous change. METHODS: OHT
      was surgically induced in 20 Dark Agouti rats. Animals were imaged using a
      modified Spectralis OCT (Heidelberg Engineering, Heidelberg, Germany) at baseline
      and at 3 and 8 weeks after OHT induction. Measurements were recorded for whole
      and individual retinal layer thickness in four regions-temporal, superior, nasal,
      and inferior-around the optic nerve head. RESULTS: Whole retinal thickness in
      normal eyes was 172.19 +/- 5.17 MUm, with no significant regional differences.
      OHT caused a significant reduction in whole retinal thickness and the outer
      nuclear layer (ONL) at 3 and 8 weeks (P < 0.05), along with the expected thinning
      of the retinal nerve fiber layer (RNFL). Whole retinal thickness correlated well
      with RNFL (P = 0.035) and ONL (P <= 0.001) changes. Sensitivity of RNFL and ONL
      to IOP exposure appeared greater at 3 than at 8 weeks. In addition, regional
      profiles were significantly altered in the ONL and RNFL after OHT induction.
      CONCLUSIONS: Adaptation of the Spectralis OCT enables tracking of structural
      damage in experimental rat OHT. Here the authors show evidence of glaucomatous
      damage in the outer retinal layers of this model with significant regional
      changes and highlight whole retinal thickness in the rat as a useful surrogate
      marker of inner and outer retinal changes. The authors believe that the OCT data
      can provide useful information with regard to clinical management.

PMID- 20688742
TI  - Downregulation of matrix metalloproteinase-2 in corneal fibroblasts by
      interleukin-1 receptor antagonist released from corneal epithelial cells.
AB  - PURPOSE: The authors previously showed that the expression of various junctional
      proteins in corneal epithelial cells or corneal fibroblasts (CFs) is regulated by
      the presence of the other cell type in a coculture system. In this study, the
      effect of corneal epithelial cells on the expression of matrix metalloproteinases
      (MMPs) in CFs was studied. METHODS: Human CFs and simian virus 40-transformed
      human corneal epithelial (HCE) cells were cultured on opposite sides of a
      collagen vitrigel membrane. Expression of MMPs in CFs was examined by reverse
      transcription-polymerase chain reaction and immunoblot analyses. RESULTS: The
      amounts of MMP-2 mRNA and protein in CFs were decreased by the presence of HCE
      cells. HCE cells had no effect on the expression of MMP-1 in CFs. HCE cells
      released interleukin (IL)-1 receptor antagonist (IL-1RA) into the culture medium,
      and depletion of IL-1RA in HCE cells by RNA interference largely abolished the
      effect of these cells on MMP-2 expression in CFs. The downregulation of MMP-2
      expression in CFs by HCE cells was blocked by an inhibitor of signaling by the
      mitogen-activated protein kinase (MAPK) ERK (PD98059) but was not affected by
      those of signaling by the MAPKs p38 (SB203580) or JNK (SP600125). CONCLUSIONS:
      Corneal epithelial cells downregulated expression of MMP-2 in CFs in a manner
      dependent at least in part on the release of IL-1RA from the former cells. This
      effect might contribute to the attenuation of corneal stromal remodeling by
      corneal epithelial cells.

PMID- 20688743
TI  - Morphometric changes in the rat optic nerve following short-term intermittent
      elevations in intraocular pressure.
AB  - PURPOSE: Intraocular pressure (IOP) fluctuations may occur in patients with
      glaucoma, but how these fluctuations affect axonal populations in the optic nerve
      and other structures in the eye has been difficult to assess. This study
      developed a rat model to evaluate the effect of intermittent controlled
      elevations in IOP on the morphology of the rat optic nerve. METHODS: IOP was
      transiently elevated for 1 hour on each of 6 days a week over 6 weeks with an
      adjustable vascular loop around the right topically anesthetized eye of Sprague
      Dawley rats. IOP was measured by pneumatonometer before, immediately after, and
      at the end of 1 hour of treatment with ligature. Globes and optic nerve segments
      were prepared for histology and morphometry. RESULTS: Mean baseline IOP of 14.9
      +/- 1.8 mm Hg increased to 35.3 +/- 2.6 mm Hg (P < 0.001) during 1-hour
      treatments and returned to 15.0 +/- 2.2 mm Hg (P = 0.84) 1 hour after completion.
      The contralateral untreated eyes had a mean IOP of 14.2 +/- 1.9 mm Hg at baseline
      and 14.6 +/- 1.9 mm Hg at the end of treatment. Nerve fiber layer thinning (22%
      25%) corresponded with a decrease (7%-10%) in soma number in the ganglion cell
      layer. Optic nerves displayed axonal degeneration with a modest axon loss of 6%
      and increased expression of glial acidic fibrillary protein in astrocytes.
      CONCLUSIONS: Controlled daily 1-hour IOP elevations can be performed with an
      adjustable vascular loop in rats. After only 6 weeks, intermittent elevations in
      IOP produce changes in optic nerve consistent with early degeneration reported in
      chronic models of glaucoma.

PMID- 20688744
TI  - Influence of saffron supplementation on retinal flicker sensitivity in early age
      related macular degeneration.
AB  - PURPOSE: To evaluate the functional effect of short-term supplementation of
      saffron, a spice containing the antioxidant carotenoids crocin and crocetin, in
      early age-related macular degeneration (AMD). METHODS: Twenty-five patients with
      AMD were randomly assigned to oral saffron 20 mg/d or placebo supplementation
      over a 3-month period and then reverted to placebo or saffron for a further 3
      months. Focal electroretinograms (fERGs) and clinical findings were recorded at
      baseline and after 3 months of saffron or placebo supplementation. fERGs were
      recorded in response to a sinusoidally modulated (41 Hz), uniform field presented
      to the macular region (18 degrees ) at different modulations between 16.5% and
      93.5%. Main outcome measures were fERG amplitude (in microvolts), phase (in
      degrees), and modulation thresholds. RESULTS: After saffron, patients' fERGs were
      increased in amplitude, compared with either baseline or values found after
      placebo supplementation (mean change after saffron, 0.25 log MUV; mean change
      after placebo, -0.003 log MUV; P < 0.01). fERG thresholds were decreased after
      saffron supplementation but not placebo, compared with baseline (mean change
      after saffron, -0.26 log units; mean change after placebo, 0.0003 log units).
      CONCLUSIONS: The results indicate that short-term saffron supplementation
      improves retinal flicker sensitivity in early AMD. Although the results must be
      further replicated and the clinical significance is yet to be evaluated, they
      provide important clues that nutritional carotenoids may affect AMD in novel and
      unexpected ways, possibly beyond their antioxidant properties.
      (ClinicalTrials.gov number, NCT00951288.).

PMID- 20688745
TI  - Novel cellular bouton structure activated by ATP in the vascular wall of porcine
      retinal arterioles.
AB  - PURPOSE: The retinal blood flow is regulated by the tone of resistance
      arterioles, which is influenced by purinergic compounds such as adenosine and
      adenosine 5'-triphosphate (ATP) released from the retinal tissue. However, it is
      unknown what cellular elements in the perivascular retina are responsible for the
      effect of purines on the tone of retinal arterioles. METHODS: Porcine retinal
      arterioles were loaded with the calcium-sensitive fluorophore Oregon green. The
      vessels were mounted in a confocal myograph for simultaneous recordings of tone
      and calcium activity in cells of the vascular wall during stimulation with ATP
      and adenosine, with and without modifiers of these compounds. Additionally,
      immunohistochemistry was used to localize elements with calcium activity in the
      vascular wall. RESULTS: Hyperfluorescence indicating calcium activity was
      recorded in a population of abundant round boutons interspersed in a network of
      vimentin-positive processes located immediately external to the smooth muscle
      cell layer but internal to the perivascular glial cells. These structures showed
      calcium activity when the vessel was relaxed with ATP but not when it was relaxed
      with adenosine. Ryanodine reduced calcium activity in the boutons, whereas the
      ATP antagonist adenosine-5'-O-(alpha, beta- methylene diphosphate) reduced
      calcium activity in both the boutons and vascular tone. CONCLUSIONS: The
      vasodilating effect of purines in porcine retinal tissue involves ATP-dependent
      calcium activity in a layer of cellular boutons located external to the vascular
      smooth muscle cells and internal to the perivascular glial cells.

PMID- 20688746
TI  - Microstructure and network organization of the microvasculature in the human
      macula.
AB  - PURPOSE: To characterize the topography and cellular structure of the macular
      microvasculature using a recently developed technique of arterial cannulation,
      perfusion, fixation, and staining of human donor eyes. METHODS: Sixteen human
      donor eyes were used. The central retinal artery was cannulated and perfused with
      Ringer's, then fixative, membrane permeabilizing, and selected labeling
      solutions. The eyes were immersion fixed, and the retina was flat mounted for
      confocal microscopy. The macular area, including the foveola, fovea, and
      parafovea, was sampled. The intracellular cytoskeleton of vascular endothelial
      and smooth muscle cells was studied in different orders of arterioles and venules
      and in the capillaries. To evaluate the degree of asymmetry within vascular
      networks, the distribution of generation numbers and the Horton-Strahler approach
      to vessel naming were compared. RESULTS: The distribution of the microvascular
      network in the macular region was complex but followed a general theme. The
      parafoveal region was supplied by dense vasculature with approximately nine
      closely arranged pairs of arterioles and venules. Each arteriole had abundant
      branches and a high degree of asymmetry (~10 generations and 3.5 orders within
      1.2-mm length). Only a few arterioles (average ~2.9) supplied the terminal
      capillary ring. Very long spindle endothelial cells were seen in the superficial
      and deep capillaries. Significant heterogeneity of distribution and shape of the
      endothelial and smooth muscle cells was evident in different orders of the
      macular vasculature. CONCLUSIONS: The authors have demonstrated for the first
      time the cellular structure and topographic features of the macular
      microvasculature in human donor eyes.

PMID- 20688748
TI  - Objections to the transfer of Francisella novicida to the subspecies rank of
      Francisella tularensis.

PMID- 20688749
TI  - Objections to the transfer of Francisella novicida to the subspecies rank of
      Francisella tularensis - response to Johansson et al.

PMID- 20688750
TI  - Dactylosporangium luridum sp. nov., Dactylosporangium luteum sp. nov. and
      Dactylosporangium salmoneum sp. nov., nom. rev., isolated from soil.
AB  - Forty strains isolated from soil taken from a hay meadow were assigned to the
      genus Dactylosporangium on the basis of colonial properties. 16S rRNA gene
      sequence analysis showed that the isolates formed a group that was most closely
      related to the type strain of Dactylosporangium aurantiacum, but well separated
      from other Dactylosporangium type strains and from 'Dactylosporangium salmoneum'
      NRRL B-16294. Twelve of 13 representative isolates had identical 16S rRNA gene
      sequences and formed a subclade that was distinct from corresponding phyletic
      lines composed of the remaining isolate, strain BK63T, the 'D. salmoneum' strain
      and the type strains of recognized Dactylosporangium species. DNA-DNA relatedness
      data indicated that representatives of the multi-membered 16S rRNA gene subclade,
      isolate BK63T and the 'D. salmoneum' subclade formed distinct genomic species;
      all of these organisms had chemotaxonomic and morphological properties consistent
      with their classification in the genus Dactylosporangium. They were also
      distinguished from one another and from the type strains of recognized
      Dactylosporangium species based on a range of phenotypic properties. Combined
      genotypic and phenotypic data showed that isolate BK63T, isolates BK51T, BK53 and
      BK69, and strain NRRL B-16294T should be classified in the genus
      Dactylosporangium as representing novel species. The names proposed for these
      species are Dactylosporangium luridum sp. nov. (type strain BK63T =DSM 45324T
      =KACC 20933T =NRRL B-24775T), Dactylosporangium luteum sp. nov. (type strain
      BK51T =DSM 45323T =KACC 20899T =NRRL B-24774T) and Dactylosporangium salmoneum
      sp. nov., nom. rev. (type strain NRRL B-16294T =ATCC 31222T =DSM 43910T =JCM
      3272T =NBRC 14103T).

PMID- 20688751
TI  - Unique cost dynamics elucidate the role of frameshifting errors in promoting
      translational robustness.
AB  - There is now considerable evidence supporting the view that codon usage is
      frequently under selection for translational accuracy. There are, however,
      multiple forms of inaccuracy (missense, premature termination, and frameshifting
      errors) and pinpointing a particular error process behind apparently adaptive
      mRNA anatomy is rarely straightforward. Understanding differences in the fitness
      costs associated with different types of translational error can help us devise
      critical tests that can implicate one error process to the exclusion of others.
      To this end, we present a model that captures distinct features of frameshifting
      cost and apply this to 641 prokaryotic genomes. We demonstrate that, although it
      is commonly assumed that the ribosome encounters an off-frame stop codon soon
      after the frameshift and costs of mis-elongation are therefore limited, genomes
      with high GC content typically incur much larger per-error costs. We go on to
      derive the prediction, unique to frameshifting errors, that differences in
      translational robustness between the 5' and 3' ends of genes should be less
      pronounced in genomes with higher GC content. This prediction we show to be
      correct. Surprisingly, this does not mean that GC-rich organisms necessarily
      carry a greater fitness burden as a consequence of accidental frameshifting.
      Indeed, increased per-error costs are often more than counterbalanced by lower
      predicted error rates owing to more diverse anticodon repertoires in GC-rich
      genomes. We therefore propose that selection on tRNA repertoires may operate to
      reduce frameshifting errors.

PMID- 20688752
TI  - Evolutionary dynamics of complete Campylobacter pan-genomes and the bacterial
      species concept.
AB  - Defining bacterial species and understanding the relative cohesiveness of
      different components of their genomes remains a fundamental problem in
      microbiology. Bacterial species tend to be comprised of both a set of core and
      dispensable genes, with the sum of these two components forming the species pan
      genome. The role of the core and dispensable genes in defining bacterial species
      and the question of whether pan-genomes are finite or infinite remain unclear.
      Here we demonstrate, through the analysis of 96 genome sequences derived from two
      closely related sympatric sister species of pathogenic bacteria (Campylobacter
      coli and C. jejuni), that their pan-genome is indeed finite and that there are
      unique and cohesive features to each of their genomes defining their genomic
      identity. The two species have a similar pan-genome size; however, C. coli has
      acquired a larger core genome and each species has evolved a number of species
      specific core genes, possibly reflecting different adaptive strategies. Genome
      wide assessment of the level of lateral gene transfer within and between the two
      sister species, as well as within the core and non-core genes, demonstrates a
      resistance to interspecies recombination in the core genome of the two species
      and therefore provides persuasive support for the core genome hypothesis for
      bacterial species.

PMID- 20688754
TI  - A simple and sensitive enzymatic method for cholesterol quantification in
      macrophages and foam cells.
AB  - A precise and sensitive method for measuring cellular free and esterified
      cholesterol is required in order to perform studies of macrophage cholesterol
      loading, metabolism, storage, and efflux. Until now, the use of an enzymatic
      cholesterol assay, commonly used for aqueous phase plasma cholesterol assays, has
      not been optimized for use with solid phase samples such as cells, due to
      inefficient solubilization of total cholesterol in enzyme compatible solvents. We
      present an efficient solubilization protocol compatible with an enzymatic
      cholesterol assay that does not require chemical saponification or
      chromatographic separation. Another issue with enzyme compatible solvents is the
      presence of endogenous peroxides that interfere with the enzymatic cholesterol
      assay. We overcame this obstacle by pretreatment of the reaction solution with
      the enzyme catalase, which consumed endogenous peroxides resulting in reduced
      background and increased sensitivity in our method. Finally, we demonstrated that
      this method for cholesterol quantification in macrophages yields results that are
      comparable to those measured by stable isotope dilution gas chromatography with
      mass spectrometry detection. In conclusion, we describe a sensitive, simple, and
      high-throughput enzymatic method to quantify cholesterol in complex matrices such
      as cells.

PMID- 20688753
TI  - Long-chain and very long-chain polyunsaturated fatty acids in ocular aging and
      age-related macular degeneration.
AB  - Retinal long-chain PUFAs (LC-PUFAs, C(12)-C(22)) play important roles in normal
      human retinal function and visual development, and some epidemiological studies
      of LC-PUFA intake suggest a protective role against the incidence of advanced age
      related macular degeneration (AMD). On the other hand, retinal very long-chain
      PUFAs (VLC-PUFAs, C(n>22)) have received much less attention since their
      identification decades ago, due to their minor abundance and more difficult
      assays, but recent discoveries that defects in VLC-PUFA synthetic enzymes are
      associated with rare forms of inherited macular degenerations have refocused
      attention on their potential roles in retinal health and disease. We thus
      developed improved GC-MS methods to detect LC-PUFAs and VLC-PUFAs, and we then
      applied them to the study of their changes in ocular aging and AMD. With ocular
      aging, some VLC-PUFAs in retina and retinal pigment epithelium (RPE)/choroid
      peaked in middle age. Compared with age-matched normal donors, docosahexaenoic
      acid, adrenic acid, and some VLC-PUFAs in AMD retina and RPE/choroid were
      significantly decreased, whereas the ratio of n-6/n-3 PUFAs was significantly
      increased. All these findings suggest that deficiency of LC-PUFAs and VLC-PUFAs,
      and/or an imbalance of n-6/n-3 PUFAs, may be involved in AMD pathology.

PMID- 20688755
TI  - Barriers to reporting medication errors: a measurement equivalence perspective.
AB  - OBJECTIVES: To demonstrate a statistical analysis for testing the measurement
      equivalence of a patient safety survey instrument. The survey instrument examined
      in the present study is the Medication Administration Error Reporting Survey.
      METHODS: Surveys were posted to a random sample of registered nurses in the State
      of Texas, with 435 nurses completing the survey. The surveys contained questions
      about various error reporting issues, including the 16-item, Medication
      Administration Error Reporting scale. Nurses were divided into one of two samples
      -calibration and holdout--to ensure replicability of the results. Within each
      sample, two groups were created based on nurse tenure on the job. RESULTS:
      Multiple Group Confirmatory Factor Analysis was conducted across nurses with
      varying levels of experience for the calibration and holdout samples. For each
      sample, a baseline model was estimated, where model parameters were allowed to
      vary across the nursing groups, and compared with more restrictive models. The
      results provided support for the factor structure of the Medication
      Administration Error Reporting System but yielded mixed results concerning the
      equivalence of the measure across nursing groups. CONCLUSIONS: The present study
      provides an explanation of how to examine the measurement equivalence of survey
      instruments and demonstrated that the Medication Administration Error Reporting
      scale might not be equivalent across nurses who differ with respect to experience
      levels.

PMID- 20688756
TI  - Metrics for monitoring local inequalities in access to maternity care: developing
      a basket of markers from routinely available data.
AB  - BACKGROUND: Equal access for all based on need is part of a conceptualisation of
      quality underpinning recent UK NHS policies. OBJECTIVE: To develop metrics for
      access to maternity care from routinely available data in order to inform
      inequalities monitoring and commissioning. DESIGN: Cross-sectional cohort design
      using case-note audit and postnatal questionnaire. SETTING: London hospital, UK,
      in an area of relative socio-economic deprivation. METHODS: Stage 1:
      Identification of potential markers. Stage 2: Testing of markers via case note
      audit and postnatal questionnaire. Stage 3: Selection of final basket of markers
      of access to maternity services. RESULTS: Of 71 possible markers identified, 32
      used information obtainable from maternity case notes. After testing in the case
      note audit, 21 were discarded, and 11 included in the final basket covering:
      timely entry to maternity care; appropriate assessment and identification of
      needs of individuals; referral and communication with other related health and
      social care services. CONCLUSION: It is possible to devise a local basket of
      markers covering a range of important entry and in-system access metrics. Such a
      tool offers an unobtrusive means to audit the effectiveness of some of the
      processes intended to help women move through the maternity and related health
      and social care systems during pregnancy, and to monitor progress on reducing
      social inequalities in access over time.

PMID- 20688757
TI  - Multidose drug dispensing and discrepancies between medication records.
AB  - BACKGROUND: The objective of this study was to investigate whether implementation
      of multidose drug dispensing (MDD) for elderly outpatients is associated with a
      change in the number of discrepancies in the medication record at the general
      practitioners (GPs) and at the community home-care services. METHODS: A
      controlled follow-up study with paired design of patients' medication records was
      performed during implementation of MDD. Medication records from the home care
      units and from the GPs were reviewed, and the discrepancies were noted. The
      discrepancies were rated into four classes based upon the potential harm, and a
      risk score system was applied, giving the potentially most harmful discrepancies
      the highest score. RESULTS: Medication records from 59 patients with a mean age
      of 80 years were included. The number of discrepancies was reduced from 203 to
      133 (p<0.001), and the total risk score decreased from 308 to 181 (p<0.001) after
      the implementation of MDD. For both drugs subject to MDD and drugs not suitable
      for MDD, the reductions in discrepancies were significant (39% and 31% reduction
      respectively). CONCLUSIONS: Calculated health risk due to discrepancies between
      the medication records from the home-care service and from the GPs decreased
      during the time of implementation of the MDD system. It seems likely that most of
      the positive effect was caused by the change in routines and enhanced focus on
      the medication process rather than by MDD per se.

PMID- 20688758
TI  - Intensive nursing work schedules and the risk of hypoglycaemia in critically ill
      patients who are receiving intravenous insulin.
AB  - RATIONALE: Nurses in the intensive care unit (ICU) commonly work frequent 12 h
      shifts, potentially leading to fatigue and reduced vigilance. The authors
      hypothesised that rates of hypoglycaemia in patients receiving an insulin
      infusion would be associated with the intensity of work of the bedside nurse in
      the preceding 72 h. METHODS: The authors identified ICU patients who had
      hypoglycaemia (glucose <=3.5 mmol/l, 63 mg/dl) between October 2006 and June
      2007. The number of shifts worked in the previous 72 h was calculated for the
      nurse caring for the patient when the event occurred (case shift). For each case
      shift, the authors identified up to three control shifts (24, 48 and 72 h before
      the event in the same patient) and calculated the number of shifts worked by
      nurses on these shifts in the previous 72 h. Conditional logistic regression was
      used to determine whether the number of shifts worked was associated with
      hypoglycaemia. RESULTS: There were 41 events (32 patients). Each additional shift
      worked in the previous 72 h was associated with a significantly increased risk of
      hypoglycaemia (OR = 1.65/shift, 95% CI 1.01 to 2.68, p = 0.04) after controlling
      for nurse age and experience. The association was greater for the 23 events
      associated with an error in management according to the insulin protocol (OR =
      2.93/shift, 1.15 to 7.44, p = 0.02) compared with events not associated with an
      error (OR = 1.34/shift, 0.73 to 2.45, p = 0.34). CONCLUSIONS: Intensive nursing
      work schedules are associated with hypoglycaemic events in ICU patients.

PMID- 20688759
TI  - Molecular basis of a linkage peak: exome sequencing and family-based analysis
      identify a rare genetic variant in the ADIPOQ gene in the IRAS Family Study.
AB  - Family-based linkage analysis has been a powerful tool for identification of
      genes contributing to traits with monogenic patterns of inheritance. These
      approaches have been of limited utility in identification of genes underlying
      complex traits. In contrast, searches for common genetic variants associated with
      complex traits have been highly successful. It is now widely recognized that
      common variations frequently explain only part of the inter-individual variation
      in populations. 'Rare' genetic variants have been hypothesized to contribute
      significantly to phenotypic variation in the population. We have developed a
      combination of family-based linkage, whole-exome sequencing, direct sequencing
      and association methods to efficiently identify rare variants of large effect.
      Key to the successful application of the method was the recognition that only a
      few families in a sample contribute significantly to a linkage signal. Thus, a
      search for mutations can be targeted to a small number of families in a
      chromosome interval restricted to the linkage peak. This approach has been used
      to identify a rare (1.1%) G45R mutation in the gene encoding adiponectin, ADIPOQ.
      This variant explains a strong linkage signal (LOD > 8.0) and accounts for ~17%
      of the variance in plasma adiponectin levels in a sample of 1240 Hispanic
      Americans and 63% of the variance in families carrying the mutation. Individuals
      carrying the G45R mutation have mean adiponectin levels that are 19% of non
      carriers. We propose that rare variants may be a common explanation for linkage
      peaks observed in complex trait genetics. This approach is applicable to a wide
      range of family studies and has potential to be a discovery tool for
      identification of novel genes influencing complex traits.

PMID- 20688764
TI  - How to do (or not to do) ... a benefit incidence analysis.
AB  - Benefit incidence analysis (BIA) considers who (in terms of socio-economic
      groups) receive what benefit from using health services. While traditionally BIA
      has focused on only publicly funded health services, to assess whether or not
      public subsidies are 'pro-poor', the same methodological approach can be used to
      assess how well the overall health system is performing in terms of the
      distribution of service benefits. This is becoming increasingly important in the
      context of the growing emphasis on promoting universal health systems. To conduct
      a BIA, a household survey dataset that incorporates both information on health
      service utilization and some measure of socio-economic status is required. The
      other core data requirement is unit costs of different types of health service.
      When utilization rates are combined with unit costs for different health
      services, the distribution of benefits from using services, expressed in monetary
      terms, can be estimated and compared with the distribution of the need for health
      care. This paper aims to provide an introduction to the methods used in the
      'traditional' public sector BIA, and how the same methods can be applied to
      undertake an assessment of the whole health system. We consider what data are
      required, potential sources of data, deficiencies in data frequently available in
      low- and middle-income countries, and how these data should be analysed.

PMID- 20688765
TI  - Growth of left heart structures following the hybrid procedure for borderline
      hypoplastic left heart.
AB  - AIMS: The 'hybrid' procedure is an alternative to the Norwood operation in
      classical hypoplastic left heart syndrome to support the systemic circulation
      until subsequent palliation. This approach has been extended to infants with the
      borderline development of left heart structures. We investigated whether or not a
      hybrid procedure for 'borderline' cases of underdevelopment of the left heart
      would lead to any improvement in the growth of those structures relative to body
      size or would impact on eventual repair. METHODS AND RESULTS: Serial
      echocardiograms were reviewed in cases in whom left heart development was judged
      borderline for adequacy to support the systemic circulation. z-scores of left
      heart structures and aortic discriminant scores were plotted sequentially
      following the hybrid procedure and random-coefficient linear-mixed models were
      applied to quantify growth rates. Seven infants met the inclusion criteria. At
      birth, the median (range) of aortic discriminant scores was -2.67 (-3.26 to 
      1.22), suggesting that a biventricular repair would not be feasible. Following a
      hybrid procedure, aortic discriminant scores increased with time and three
      infants were managed with a biventricular repair. The rate of change was
      significantly higher in infants who achieved a biventricular repair compared with
      those who did not (P = 0.01). CONCLUSION: The hybrid procedure allows time for
      growth of left heart structures in selected infants, and serial echocardiography
      may assist in identifying those children who may ultimately achieve a
      biventricular circulation.

PMID- 20688766
TI  - Estimation of left ventricular filling pressures by speckle tracking
      echocardiography in patients with idiopathic dilated cardiomyopathy.
AB  - AIMS: the ratio of early diastolic transmitral flow velocity (E) to early
      diastolic mitral annular velocity (E(a)) is frequently used to predict an
      increase in left ventricular filling pressure (LVFP). However, this approach has
      several limitations. The aim of this study was to test whether additional
      information is gained by new echocardiographic indexes utilizing strain and
      strain rate (SR) derived from 2-dimensional speckle tracking echocardiography (2D
      STE) for the estimation of LVFP. METHODS AND RESULTS: fifty-one patients with
      idiopathic dilated cardiomyopathy (IDC) underwent pulsed-wave tissue Doppler
      echocardiography and 2D-STE performed simultaneously with right heart
      catheterization. Receiver operating characteristic analysis showed that
      circumferential strain and the SR during late diastolic LV filling (0.956 and
      0.951, both P = 0.001), E/circumferential SR at early diastolic LV filling
      (0.949, P = 0.001), and E/circumferential strain at the time of peak E-wave
      (0.948, P = 0.001) had greater area under the curve than the E/E(a) ratio (0.911,
      P = 0.001) for the prediction of pulmonary capillary wedge pressure > 12 mmHg.
      CONCLUSION: when compared with the E/E(a) ratio, several 2D-STE-derived
      parameters better estimated the increase in LVFP in patients with IDC.

PMID- 20688768
TI  - Transepithelial exit of leucocytes: inflicting, reflecting or resolving airway
      inflammation?
AB  - The passage of infiltrated tissue granulocytes across airway epithelium into
      airway lumen is generally considered to be a pathogenic process in asthma and
      chronic obstructive pulmonary disease (COPD). An alternative hypothesis is
      proposed here-namely that the transepithelial egression of infiltrated leucocytes
      acts to rid diseased airway tissues of proinflammatory cells efficiently and non
      injuriously. Several clinical observations previously discussed as 'unexpected'
      and 'puzzling' support this hypothesis. In acutely resolving allergen challenge
      induced inflammation, in patients with mild asthma, airway wall eosinophils
      disappear without evidence of apoptosis but with evidence of a developing airway
      lumen eosinophilia. In the same postchallenge resolution phase, lymphocytes,
      neutrophils and mast cells exhibit peak numbers in airway lumen of individuals
      with asthma. In severe asthma requiring intubation, clinical improvement is
      similarly parallelled by a marked increase over several days in airway lumen
      neutrophils. Increased numbers of sputum neutrophils and lymphocytes also occur
      as symptoms improve in COPD over several months after smoking cessation.
      Conversely, when the transepithelial exit of leucocytes has been inhibited in
      inflamed animal airways the inflammation in the airway wall has been much
      aggravated. Finally, transepithelial egression of numerous granulocytes and
      lymphocytes clearly can occur without any harm to airway epithelial barriers. The
      present hypothesis of 'resolution through egression' provides a novel
      interpretation of common airway lumen data, cautions against administration of
      agents that impede leucocyte egression in inflammatory airway diseases and infers
      new approaches in disease resolution research.

PMID- 20688767
TI  - Recommendations for transoesophageal echocardiography: update 2010.
AB  - Transoesophageal echocardiography (TOE) is a standard and indispensable technique
      in clinical practice. The present recommendations represent an update and
      extension of the recommendations published in 2001 by the Working Group on
      Echocardiography of the European Society of Cardiology. New developments covered
      include technical advances such as 3D transoesophageal echo as well as developing
      applications such as transoesophageal echo in aortic valve repair and in valvular
      interventions, as well as a full section on perioperative TOE.

PMID- 20688769
TI  - Invasive Neisseria meningitidis with decreased susceptibility to fluoroquinolones
      in South Africa, 2009.

PMID- 20688770
TI  - Hepatitis C virus directly acting antivirals: current developments with NS3/4A
      HCV serine protease inhibitors.
AB  - Chronic hepatitis C virus (HCV) infection is a global health problem, but the
      current therapy is effective in <50% of patients infected with genotype 1. With
      advances in cell culture systems over the past decade, the development of
      directly acting antivirals (DAAs) for HCV has become possible. There are
      currently >50 active clinical trials in this therapeutic area and NS3/4A protease
      inhibitors are now entering Phase III study. To date, we have learned that DAAs
      are potent inhibitors of HCV replication, resulting in rapid declines in serum
      HCV RNA levels, and have the potential to allow shortening of therapy. However,
      these agents drive selective pressure for mutant viruses that can develop rapidly
      and have reduced susceptibility to the drug. Therefore, for now, the current
      standard of care including pegylated interferon alpha (pegIFN) and ribavirin
      remains a crucial part of new drug development. Furthermore, the adverse event
      profile for the early DAAs has added to the concerns of tolerability that are so
      common for the current standard of care. Ongoing issues include the optimal
      duration of therapy, how and when to combine DAAs, and the long-term role of
      pegIFN and ribavirin. Here, we summarize the current information regarding the
      effectiveness of protease inhibitors in treating chronic HCV and discuss the key
      challenges now facing the field.

PMID- 20688772
TI  - Ambulatory surgery center market share and rates of outpatient surgery in the
      elderly.
AB  - Relative to outpatient surgery in hospital settings, ambulatory surgery centers
      (ASCs) are more efficient and associated with a lower cost per case. However,
      these facilities may also spur higher overall procedure utilization and thus lead
      to greater overall health care costs. The authors used the State Ambulatory
      Surgery Database from the State of Florida to identify Medicare-aged patients
      undergoing 4 common ambulatory procedures in 2006, including knee arthroscopy,
      cystoscopy, cataract removal, and colonoscopy. Hospital service areas (HSAs) were
      characterized according to ASC market share, that is, the proportion of residents
      undergoing outpatient surgery in these facilities. The authors then examined
      relationships between ASC market share and rates of each procedure. Age-adjusted
      rates of ambulatory surgery ranged from 190.5 cases per 1000 to 320.8 cases per
      1000 in HSAs with low and high ASC market shares, respectively (P < .01). For all
      4 procedures, adjusted rates of procedures were significantly higher in HSAs with
      the highest ASC market share. The greatest difference, both in relative and
      absolute terms, was observed for patients undergoing cystoscopy. In areas of high
      ASC market share, the age-adjusted rate of cystoscopy was nearly 3-fold higher
      than in areas with low ASC market share (34.5 vs 11.9 per 1000 population; P <
      .01). The presence of an ASC is associated with higher utilization of common
      outpatient procedures in the elderly. Whether ASCs are meeting unmet clinical
      demand or spurring overutilization is not clear.

PMID- 20688773
TI  - Guidelines for the management of obstructive hydrocephalus from suprasellar
      prepontine arachnoid cysts using endoscopic third ventriculocystocisternostomy.
AB  - Intracranial endoscopy has emerged as an innovative surgical tool for various
      intracranial procedures, but its use remains limited to neurosurgeons trained in
      this minimally invasive technique. Complex, skull base arachnoid cysts represent
      one entity that is challenging to treat because of adjacent critical
      neurovascular structures; however, the advent of intracranial endoscopic
      techniques has revolutionized treatment. Arachnoid cysts located in the
      suprasellar-prepontine skull base region can cause obstructive hydrocephalus or
      symptomatic mass effect and require urgent decompression. These patients may
      present with nonfocal symptoms that can quickly lead to a life-threatening
      condition if not accurately diagnosed and treated. The authors present a summary
      of the world literature of suprasellar-prepontine arachnoid cysts (SPACs) to
      ascertain clinical presentations and provide class III evidentiary treatment
      guidelines for this uniquely challenging type of arachnoid cyst. Urgent
      endoscopic third ventriculostomy results in normalization of intracranial
      pressure, return of normal CSF flow, and relief of symptoms.

PMID- 20688771
TI  - Race differences in access to health care and disparities in incident chronic
      kidney disease in the US.
AB  - BACKGROUND: The contribution of race differences in access to health care to
      disparities in chronic kidney disease (CKD) incidence in the United States is
      unknown. METHODS: We examined race differences in usual source of health care,
      health insurance and CKD incidence among 3883 Whites and 1607 Blacks with
      hypertension or diabetes enrolled in the Atherosclerosis Risk in Communities
      Study. In multivariable analyses, we explored the incremental contribution of
      access to health care in explaining Blacks' excess CKD incidence above and beyond
      other socioeconomic, lifestyle and clinical factors. RESULTS: Compared with
      Whites, Blacks had poorer access to health care (3 vs 0.3% with no usual source
      of health care or health insurance, P < 0.001) and experienced greater CKD
      incidence (14.7 vs 12.0 cases per 1000 person-years, P < 0.001). Blacks' excess
      risk of CKD persisted after adjusting for demographic, socioeconomic, lifestyle
      and clinical factors [hazard ratio (HR) (95% confidence interval (95% CI)) = 1.21
      (1.01-1.47)]. Adjustment for these factors explained 64% of the excess risk among
      Blacks. The increased risk for CKD among Blacks was attenuated after additional
      adjustment for race differences in access to health care [HR (95% CI) = 1.19
      (0.99-1.45)], which explained an additional 10% of the disparity. Conclusions. In
      this population at risk for developing CKD, we found that poorer access to health
      care among Blacks explained some of Blacks' excess risk of CKD, beyond the excess
      risk explained by demographic, socioeconomic, lifestyle and clinical factors.
      Improved access to health care for high-risk individuals could narrow disparities
      in CKD incidence.

PMID- 20688774
TI  - The axillary artery--a new approach for endovascular treatment of thoracic aortic
      diseases.
AB  - Endovascular procedures are increasing in number for the treatment of thoracic
      aortic diseases (TAD). Retrograde approach through the femoral artery is the
      preferred vascular access. Despite the improvements in the devices, femoral
      artery complications still occurs and some times this access is not possible
      because of the small size of the vessels, obstruction, calcification, dissection
      or extreme tortuosity. An axillary approach could be an alternative. We present a
      series of five patients and describe the technique we used in the axillary artery
      approach to treat TAD. There were two ascending aortas and three descending
      aortic aneurysms treated. The left axillary artery was used in three patients and
      the right in two. There were no local or neurological complications. In this
      preliminary approach, both axillary arteries were a good alternative access for
      endovascular graft insertion to treat aortic diseases when femoral access was not
      possible or was suboptimal.

PMID- 20688775
TI  - Role of magnesium in the prevention of postoperative arrhythmias in neonates and
      infants undergoing arterial switch operation.
AB  - The objectives of the study were to measure magnesium levels in neonates and
      infants undergoing arterial switch operation and to ascertain the role of
      magnesium supplementation in the prevention of postoperative arrhythmias. Group I
      (n=25): magnesium was administered in the dose of 30 mg/kg over 10 minutes in
      normal saline (5 ml) immediately after cessation of cardiopulmonary bypass (CPB).
      Group II (n=25): normal saline (5 ml) was administered over 10 minutes
      immediately after cessation of CPB. Samples of arterial blood were collected at
      four time points: 1) after induction of anaesthesia; 2) 10 minutes after
      initiation of CPB; 3) at rewarming during CPB; and 4) 4 hours after shifting the
      patient to the intensive care unit. Samples were measured for ionized magnesium
      (iMg), blood gases, haematocrit level, electrolytes, ionized calcium and glucose.
      Continuous ECG rhythm analysis and documentation of arrhythmias was performed for
      24 hours after surgery. The mean preoperative iMg levels were below the normal
      level in both the groups. A significant increase in iMg levels (P=0.00) was seen
      in both groups during rewarming. There is no statistically significant difference
      in the incidence of arrhythmias between the magnesium supplemented group (4%) and
      the control group (20%) in the postoperative period, a tendency towards reduction
      in arrhythmias was only observed in the magnesium supplemented group.

PMID- 20688776
TI  - Cavitating pulmonary tuberculosis four years postexcision of a very large
      thymoma.
AB  - Lipothymoma is a very rare thymic benign tumor. A 55-year-old male, who underwent
      thymectomy four years previously, presented with cavitating pulmonary
      tuberculosis.

PMID- 20688777
TI  - Involvement of a psychiatric consultation service in a palliative care team at
      the Japanese cancer center hospital.
AB  - OBJECTIVE: Close collaboration between the cancer care team service and the
      psychiatric consultation service is recommended to provide adequate comprehensive
      care to cancer patients. In Japan, specialized palliative care teams work in
      conjunction with consultation-liaison psychiatrists as an essential members.
      There are, however, few studies reporting on these services. METHODS: We obtained
      the characteristics, physical and psychiatric symptoms and outcomes of cancer
      patients by analyzing the database of patients referred to the palliative care
      team at the National Cancer Center Hospital East, Japan. RESULTS: Among
      consecutive 2000 referrals, most patients referred to the palliative care team
      present both physical and psychiatric symptoms. Psychiatric diagnoses were
      provided for ~70% of these patients. Consultation-liaison psychiatrists provided
      medical care to 80% of all the referrals. The main symptoms for psychiatric
      consultation were delirium (28%), adjustment disorder (18%), major depression
      (7.6%) and dementia (6.6%). CONCLUSIONS: Psychiatric problems are common in
      cancer patients of the palliative care team. The palliative care team should
      assess the psychiatric problems in cancer patients, and the involvement of the
      consultation-liaison psychiatrists in the palliative care teams may be one of the
      strategies to establish the psychosocial support for cancer patients in the acute
      hospital settings.

PMID- 20688778
TI  - Hepatic arterial infusion therapy with a fine powder formulation of cisplatin for
      advanced hepatocellular carcinoma with portal vein tumor thrombosis.
AB  - OBJECTIVE: We retrospectively evaluated the antitumor effect, survival and
      toxicities of hepatic arterial infusion therapy using a fine powder formulation
      of cisplatin (cisplatin powder) in hepatocellular carcinoma patients with portal
      vein tumor thrombosis. METHODS: Twenty-four patients classified as Child-Pugh
      class A or B underwent a single session of hepatic arterial infusion therapy
      using cisplatin powder. The treatment was repeated every 4-6 weeks in patients
      with no evidence of tumor progression or unacceptable toxicity. The treatment
      response was evaluated using contrast-enhanced computed tomography performed 1
      month after each treatment. The survival rate was evaluated using the Kaplan
      Meier method, and predictors of a better outcome were identified using univariate
      analysis. RESULTS: The mean follow-up period was 11.2 months (range, 1.3-44.2
      months). A total of 57 sessions of intra-arterial infusion (1-6 sessions per
      patient; mean, 2.4 sessions) with cisplatin powder were performed. A complete
      response and a partial response were obtained in one and four patients,
      respectively (objective response rate = 20.8%). The median survival time for all
      the patients was 7.0 months; the median survival times for the 5 responders and
      19 non-responders were 37.3 and 5.6 months, respectively. The 1- and 2-year
      survival rates were 38% and 16%, respectively. Significant prognostic factors
      related to survival were the therapeutic effect, patient age and serum alanine
      aminotransferase level. Severe adverse reactions resulting in treatment
      discontinuation were not observed, and all the toxicities were successfully
      managed using conservative treatment. CONCLUSIONS: Hepatic arterial infusion
      therapy with a fine powder formulation of cisplatin was safe, well-tolerated and
      might help to prolong the life span of advanced hepatocellular carcinoma patients
      with portal vein tumor thrombosis.

PMID- 20688779
TI  - Genome-wide mapping of nuclear mitochondrial DNA sequences links DNA replication
      origins to chromosomal double-strand break formation in Schizosaccharomyces
      pombe.
AB  - Chromosomal double-strand breaks (DSBs) threaten genome integrity and repair of
      these lesions is often mutagenic. How and where DSBs are formed is a major
      question conveniently addressed in simple model organisms like yeast. NUMTs,
      nuclear DNA sequences of mitochondrial origin, are present in most eukaryotic
      genomes and probably result from the capture of mitochondrial DNA (mtDNA)
      fragments into chromosomal breaks. NUMT formation is ongoing and was reported to
      cause de novo human genetic diseases. Study of NUMTs is likely to contribute to
      the understanding of naturally occurring chromosomal breaks. We show that
      Schizosaccharomyces pombe NUMTs are exclusively located in noncoding regions with
      no preference for gene promoters and, when located into promoters, do not affect
      gene transcription level. Strikingly, most noncoding regions comprising NUMTs are
      also associated with a DNA replication origin (ORI). Chromatin
      immunoprecipitation experiments revealed that chromosomal NUMTs are probably not
      acting as ORI on their own but that mtDNA insertions occurred directly next to
      ORIs, suggesting that these loci may be prone to DSB formation. Accordingly,
      induction of excessive DNA replication origin firing, a phenomenon often
      associated with human tumor formation, resulted in frequent nucleotide deletion
      events within ORI3001 subtelomeric chromosomal locus, illustrating a novel aspect
      of DNA replication-driven genomic instability. How mtDNA is fragmented is another
      important issue that we addressed by sequencing experimentally induced NUMTs.
      This highlighted regions of S. pombe mtDNA prone to breaking. Together with an
      analysis of human NUMTs, we propose that these fragile sites in mtDNA may
      correspond to replication pause sites.

PMID- 20688780
TI  - Susceptibility to chronic pain following nerve injury is genetically affected by
      CACNG2.
AB  - Chronic neuropathic pain is affected by specifics of the precipitating neural
      pathology, psychosocial factors, and by genetic predisposition. Little is known
      about the identity of predisposing genes. Using an integrative approach, we
      discovered that CACNG2 significantly affects susceptibility to chronic pain
      following nerve injury. CACNG2 encodes for stargazin, a protein intimately
      involved in the trafficking of glutamatergic AMPA receptors. The protein might
      also be a Ca(2+) channel subunit. CACNG2 has previously been implicated in
      epilepsy. Initially, using two fine-mapping strategies in a mouse model
      (recombinant progeny testing [RPT] and recombinant inbred segregation test
      [RIST]), we mapped a pain-related quantitative trait locus (QTL) (Pain1) into a
      4.2-Mb interval on chromosome 15. This interval includes 155 genes. Subsequently,
      bioinformatics and whole-genome microarray expression analysis were used to
      narrow the list of candidates and ultimately to pinpoint Cacng2 as a likely
      candidate. Analysis of stargazer mice, a Cacng2 hypomorphic mutant, provided
      electrophysiological and behavioral evidence for the gene's functional role in
      pain processing. Finally, we showed that human CACNG2 polymorphisms are
      associated with chronic pain in a cohort of cancer patients who underwent breast
      surgery. Our findings provide novel information on the genetic basis of
      neuropathic pain and new insights into pain physiology that may ultimately enable
      better treatments.

PMID- 20688781
TI  - Vitamin D deficiency is associated with sudden cardiac death, combined
      cardiovascular events, and mortality in haemodialysis patients.
AB  - AIMS: Dialysis patients experience an excess mortality, predominantly of sudden
      cardiac death (SCD). Accumulating evidence suggests a role of vitamin D for
      myocardial and overall health. This study investigated the impact of vitamin D
      status on cardiovascular outcomes and fatal infections in haemodialysis patients.
      METHODS AND RESULTS: 25-hydroxyvitamin D [25(OH)D] was measured in 1108 diabetic
      haemodialysis patients who participated in the German Diabetes and Dialysis Study
      and were followed up for a median of 4 years. By Cox regression analyses, we
      determined hazard ratios (HR) for pre-specified, adjudicated endpoints according
      to baseline 25(OH)D levels: SCD (n = 146), myocardial infarction (MI, n = 174),
      stroke (n = 89), cardiovascular events (CVE, n = 414), death due to heart failure
      (n = 37), fatal infection (n = 111), and all-cause mortality (n = 545). Patients
      had a mean age of 66 +/- 8 years (54% male) and median 25(OH)D of 39 nmol/L
      (interquartile range: 28-55). Patients with severe vitamin D deficiency [25(OH)D
      of <= 25 nmol/L] had a 3-fold higher risk of SCD compared with those with
      sufficient 25(OH)D levels >75 nmol/L [HR: 2.99, 95% confidence interval (CI):
      1.39-6.40]. Furthermore, CVE and all-cause mortality were strongly increased (HR:
      1.78, 95% CI: 1.18-2.69, and HR: 1.74, 95% CI: 1.22-2.47, respectively), all
      persisting in multivariate models. There were borderline non-significant
      associations with stroke and fatal infection while MI and deaths due to heart
      failure were not meaningfully affected. CONCLUSION: Severe vitamin D deficiency
      was strongly associated with SCD, CVE, and mortality, and there were borderline
      associations with stroke and fatal infection. Whether vitamin D supplementation
      decreases adverse outcomes requires further evaluation.

PMID- 20688782
TI  - Importance of protocols for simulation studies in clinical drug development.
AB  - Clinical trial simulation studies can be used to assess the impact of many
      aspects of trial design, conduct, analysis and decision making on trial
      performance metrics. Simulation studies can play a vital role in improving the
      efficiency of the drug development process within the pharmaceutical industry,
      but only if they are well designed and conducted. It is imperative therefore that
      a protocol or simulation plan is developed, documenting how the simulation study
      is to be conducted, analysed and reported. This article emphasises the specific
      considerations necessary for designing good quality simulation studies. These
      include defining data generation processes, data analytic methods, decision
      criteria and also determining the presentation of results for all intended
      audiences. With clinical trial simulations becoming a vital part of the drug
      development process, the protocol for clinical trial simulations may in future
      become part of the regulatory peer review process. More rigour in the planning
      and execution of simulation studies will ensure that the design, analysis and
      decision-making process for the subsequent clinical trial is based on credible
      evidence that can be independently verified.

PMID- 20688783
TI  - The perceived sexual health needs of looked after young people: findings from a
      qualitative study led through a partnership between public health and health
      psychology.
AB  - BACKGROUND: Looked after young people (LAYP) have poorer sexual health outcomes
      than their peers. However, research seldom examines the health needs of, or
      intervenes with, this group. The aim of the current study was to identify LAYP's
      perceived sexual health needs and explore sources of sexual health information,
      knowledge levels, concerns and service preferences. METHODS: Looked after young
      people within Fife, Scotland, were recruited through their workers and carers to
      participate in qualitative semi-structured interviews. Those aged 12-19 years
      were targeted for recruitment. National Health Services ethics approval was
      granted. Thematic analysis was conducted using NVivo. RESULTS: Interviews were
      conducted with 10 LAYP. Key themes included gaps in knowledge, and gaps between
      knowledge and behaviour. Being 'looked after' may have negative consequences on
      knowledge, sources of support and safer sex. A flexible, one-to-one service,
      aimed at several lifestyle issues, not solely sexual health, was preferred by
      respondents. CONCLUSION: Looked after young people require support to bridge the
      gap between knowledge and behaviour and several theories relevant to the findings
      have been identified. Participants desired more support around a range of health
      issues, which may come from school, workers and carers, as well as health
      professionals. Further research examining effective interventions with this group
      is crucial to improve outcomes.

PMID- 20688785
TI  - Screening and intervention for domestic violence during pregnancy care: a
      systematic review.
AB  - Domestic violence (DV) against women during pregnancy affects many women and
      unborn infants worldwide. Pregnancy presents a window of opportunity for health
      care providers to identify DV and provide appropriate intervention. The aim of
      this systematic review was to appraise the effectiveness of DV screening and
      interventions for women identified for DV through screening in pregnancy. The
      Cochrane Library, EMBASE, MEDLINE, and PsycINFO were searched from January 1995
      to November 2009 to identify potentially relevant studies. Studies using any
      comparative methodology from both national and international arenas were included
      but had to be in the English language. Nine studies (13 references) met the
      inclusion criteria, five for screening and four for interventions. Of the five
      screening studies, the identification of DV was significantly higher compared to
      studies that used a nonstandardized screen or no screen at all. There was also
      evidence that recurrent screening throughout the pregnancy further increased
      identification rates. There was some evidence that interventions for pregnant
      women who had experienced DV reduced the amount of violence experienced by these
      women, but the evidence is very limited by the small number of randomized studies
      with small participant numbers. Further research is required to establish the
      most effective interventions for women who are identified at risk of DV during
      pregnancy.

PMID- 20688784
TI  - Neural-specific alpha3-fucosylation of N-linked glycans in the Drosophila embryo
      requires fucosyltransferase A and influences developmental signaling associated
      with O-glycosylation.
AB  - Addition of fucose (Fuc) to glycoprotein N-linked glycans or in O-linkage
      directly to Ser/Thr residues modulates specific cell-cell interactions and cell
      signaling events. Vertebrates and invertebrates add Fuc in alpha6-linkage to the
      reducing terminal N-acetylglucosamine residue of N-glycans. In Drosophila and
      other invertebrates, Fuc can also be added in alpha3-linkage to the same residue.
      These difucosylated N-glycans are recognized by anti-horseradish peroxidase (anti
      HRP) antisera, providing a well-established marker for insect neural tissue. To
      understand the mechanisms and consequences of tissue-specific glycan expression,
      we identified a single alpha3-fucosyltransferase (FucTA) that produces the anti
      HRP epitope in Drosophila embryos. FucTA transcripts are temporally and spatially
      restricted to cells that express the anti-HRP epitope and are missing in a mutant
      that lacks neural alpha3-fucosylation. Transgenic expression of FucTA, but not of
      any other candidate alpha3-fucosyltransferase, rescues the anti-HRP epitope in
      the embryonic nervous system of this mutant. Mass spectrometric characterization
      of the N-glycans of Drosophila embryos overexpressing FucTA confirms that this
      enzyme is indeed responsible for the biosynthesis of difucosylated glycans in
      vivo. Whereas ectopic expression of FucTA in the larval wing disc produces mild
      wing notching, the heterochronic, pan-neural expression of FucTA in early
      differentiating neurons generates neurogenic and cell migration phenotypes; this
      latter effect is associated with reduced GDP-Fuc levels in the embryo and
      indicates that the diversion of fucosylation resources towards fucosylation of N
      glycans has an impact on developmental signaling associated with O-fucosylation.

PMID- 20688786
TI  - Side differences of carotid intima-media thickness in predicting cardiovascular
      events among patients with coronary artery disease.
AB  - Population-based studies have demonstrated differences in intima-media thickness
      (IMT) measured from the left and right common carotid arteries (CCAs). However,
      its prognostic implications among patients with established coronary artery
      disease (CAD) remain unknown. Correlations between the left and right CCAs and
      the composite end point of cardiac death or nonfatal acute coronary syndrome
      among 149 patients with angiographically confirmed stable CAD were studied. A
      total of 22 patients had cardiovascular events during the 32.1 +/- 10.9 months
      follow-up. Multivariate analysis revealed that prior ischemic stroke (hazard
      ratio [HR]: 15.36, 95% confidence interval [CI]: 4.49-52.59, P < .001), extent of
      CAD (HR: 1.56, 95%CI: 1.01-2.42, P = .046), and right CCA IMT (HR: 17.07, 95%CI:
      2.16-134.69, P = .007) but not the left CCA IMT, independently predicted
      cardiovascular events. The right CCA IMT independently predicted event-free
      survival among patients with established CAD, suggesting that the left and right
      CCA may exhibit different prognostic values in our population.

PMID- 20688787
TI  - Reoxygenation attenuates the adhesion of neutrophils to microvascular endothelial
      cells.
AB  - In humans, the pathophysiological inflammation response subsequent to hypoxia and
      reoxygenation often leads to systemic inflammation and multiorgan failure. We
      applied a newly developed static interaction model using human polymorphonuclear
      neutrophils and microvascular endothelial cells to clarify the role of hypoxia
      and hypoxia/reoxygenation in vitro. Human dermal microvascular endothelial cell
      cultures (n = 7) were exposed to hypoxia and different reoxygenation periods and
      the adherence rate of neutrophils to the endothelial cells as well as to the
      protein matrix on the culture slide surface were determined by quantitative
      microscopy. Hypoxia clearly triggered neutrophil adhesion to human dermal
      microvascular endothelial cells whereas additional reoxygenation significantly
      decreased neutrophil adhesion. These in vitro findings suggest that systemic
      inflammation caused by increased neutrophil adherence to the microvascular
      endothelium is already initiated by hypoxia rather than by subsequent
      reoxygenation.

PMID- 20688788
TI  - Femoral/axillary volume flow ratio as a new index for the assessment of iliac
      atherosclerosis.
AB  - OBJECTIVE: To measure the arterial volume flow (VF) with duplex scan, calculate
      femoral/axillary VF ratio, and discuss its applicability as a new index for the
      hemodynamic significance of an aorto-iliac occlusive lesion. METHODS: Several
      measures of VF were obtained consecutively with duplex scan in both common
      femoral and axillary arteries of healthy volunteers with no signs of
      atherosclerosis and patients with documented evidence of occlusive aorto-iliac
      disease with segmental pressure measurement. Then the patient group was sent to
      complimentary evaluation for a second confirmatory examination. RESULTS: There
      were a total of 635 measures of VF performed in 10 healthy volunteers and 8
      patients with severe iliac stenoses or occlusion, 2 of then with bilateral
      disease. When comparing normal participants and patients with severe iliac
      stenoses or occlusion, there was statistical significant difference between these
      2 groups (P < .01 Mann-Whitney). Similar result was found when comparing patient
      with diseased limbs with their own contralateral normal side (P < .05 Wilcoxon).
      And measuring the VF only during the systolic phase was a much more sensitive
      parameter for differentiating the normal from the diseased. Besides that a good
      correlation between proximal thigh pressure index and femoral/axillary systolic
      flow ratio was found in the patient group (P < .01 Spearman correlation).
      CONCLUSION: The femoral/axillary VF ratio is useful in assessing the hemodynamic
      significance of aorto-iliac disease, and the systolic femoral-axillary ratio may
      also be useful as a follow-up tool.

PMID- 20688789
TI  - Does patients' choice of health centre doctor depend on the organization? A
      comparative study of four municipalities with different forms of service
      provision in Finland.
AB  - AIMS: The aim of the study was to examine the use of physician services and the
      willingness to choose an health centre (HC) doctor rather than an alternative
      (i.e. private, occupational healthcare, other doctor) by the working age
      population in four municipalities in Finland. In a Southern municipality primary
      health care was contracted out to a non-profit organization whereas Eastern,
      Western and South-Western municipalities mainly provided services themselves.
      METHODS: A mail survey of a random sample of the 15-64-age population was
      conducted in 2002 (n = 2,000, response rate 62%). Data were analyzed using
      descriptive statistics as well as bi- and multivariate logistic regression
      analyses. RESULTS: Of the respondents, 69% had visited an HC doctor during the
      past year, and of these, more than 40% had also visited another doctor outside
      the HC. The willingness to choose an HC doctor varied from 40% to 54% and was
      highest in the Southern municipality. When significantly associated variables -
      age, working status, perceived stress in life situation, access to an
      appointment, perceived interpersonal quality, and visits to doctors - were
      controlled for, the willingness to choose an HC doctor was, compared with the
      Southern municipality, less popular only in the Western municipality.
      CONCLUSIONS: The tendency to choose an HC doctor rather than an alternative was
      quite low, probably reflecting lack of attractiveness of HC to patients. However,
      contracting out service production did not additionally decrease patients'
      willingness to choose an HC doctor. More attention should be paid to improving
      access, interpersonal quality and continuity of care.

PMID- 20688790
TI  - Systemic conditions associated with areca nut usage: a literature review.
AB  - AIM: The adverse effects of areca nut (AN) chewing habit on oral health have been
      reported. However, the hazards related to the habit are not restricted to the
      oral cavity but they can also jeopardise the systemic health. Since no review
      reporting the harmful effects of AN chewing on systemic health is yet available,
      the aim of the present study was to review the systemic conditions associated
      with AN usage. METHODS: To address the focused question ''What are the
      deleterious effects of AN usage on systemic health?'', the MEDLINE PubMed
      databases were explored from 1966 up to and including May 2010. The eligibility
      criteria included: human studies, individuals using AN, use of controls, and
      articles published in English. Hand-searching was also performed. Unpublished
      data was excluded. RESULTS: The review included 28 articles. Seven studies
      associated AN chewing with cardiovascular disorders and three studies related the
      habit with cerebrovascular disorders. Eight studies related AN chewing with
      obesity, hyperglycaemia, metabolic syndrome, and type 2 diabetes mellitus. Five
      studies related AN chewing with the development of hepatic disorders. Two studies
      associated the chewing habit with oesophageal inflammation and fibrosis. Three
      studies associated AN chewing with respiratory discomfort. Renal disorders were
      related with the chewing abuse in two studies. Two studies showed an adverse
      effect of AN chewing on birth outcome. CONCLUSIONS: AN chewing adversely affects
      systemic health by damaging the vital organs.

PMID- 20688791
TI  - High temperatures and health outcomes: a review of the literature.
AB  - AIMS: To analyse the relationship between high temperatures and population health
      impacts, in terms of mortality and morbidity. METHODS: A literature search was
      conducted using Medline to collect data from studies on heat waves, temperature
      health impacts curve, risk factors, and preventive measures. All the data
      collected was published in English and available up to December 2009. RESULTS:
      Numerous studies carried out in Europe following the 2003 heat wave, as well as
      those conducted prior to this date in Europe and North America, showed an
      increase in heat wave-related excess mortality. Recent studies have demonstrated
      that a forward shift of deaths may only explain a very limited quantity of the
      excess mortality observed (up to 15%) during major heat waves. Moreover, the
      results seem to exclude that ozone acts as a confounding variable, whilst it
      remains a potential effect modifier. CONCLUSIONS: Future research needs to
      explore the consistency of results in new settings, to quantify the burden of
      heat-related morbidity and in particular to evaluate the effectiveness of the
      implemented preventive measures.

PMID- 20688792
TI  - Review Article: Mapping of children's health and development data on population
      level using the classification system ICF-CY.
AB  - AIM: The aim of this study was to investigate if essential health and development
      data of all children in Sweden in the Child Health Service (CHS) and School
      Health Service (SHS) can be linked to the classification system International
      Classification of Functioning, Disability and Health--Children and Youth (ICF
      CY). METHOD: Lists of essential health terms, compiled by professionals from CHS
      and SHS, expected to be used in the national standardised records form the basis
      for the analysis in this study. The essential health terms have been linked to
      the codes of ICF-CY by using linking rules and a verification procedure. RESULTS:
      After exclusion of terms not directly describing children's health, a majority of
      the health terms could be linked into the ICF-CY with a high proportion of terms
      in body functions and a lower proportion in activity/participation and
      environment respectively. Some health terms had broad description and were linked
      to several ICF-CY codes. The precision of the health terms was at a medium level
      of detail. CONCLUSION: ICF-CY can be useful as a tool for documenting child
      health. It provides not only a code useful for statistical purposes but also a
      language useful for the CHS and SHS in their work on individual as well as
      population levels. It was noted that the health terms used by services mainly
      focused on health related to body function. This indicates that more focus is
      needed on health data related to child's functioning in everyday life situations.

PMID- 20688793
TI  - The impact of Finnish tobacco legislation on restaurant workers' exposure to
      tobacco smoke at work.
AB  - AIMS: To evaluate the impact of Finnish tobacco legislation concerning
      restaurants, questionnaire surveys were carried out four times between 1999 and
      2007. Their purpose was to assess the effects of the legislation on employees'
      exposure to tobacco smoke in bars and restaurants in Finland before the total
      prohibition of smoking. METHODS: National questionnaire surveys on reported
      exposure to tobacco smoke among restaurant workers were conducted in 1999, 2001,
      2003, and in the spring of 2007 just before the total smoking ban. RESULTS: The
      data show that smoking is more common among restaurant workers than in the
      Finnish population in general. Reported exposure to tobacco smoke in bars and
      restaurants declined slowly after the launch of the renewed Tobacco Act. Between
      1999 and 2007, it decreased from 73% to 43% among waiters who were exposed for
      over four hours per work shift and from 93% to 67% among bartenders. At the same
      time, non-exposed waiters increased from 15% to 39% and bartenders from 5% to
      10%. The number of daily smoked cigarettes, however, remained the same among
      restaurant workers during the seven-year follow-up. CONCLUSIONS: We conclude that
      the reform of the Finnish tobacco legislation in 2000, which did not totally
      prohibit smoking in restaurants, decreased the exposure to environmental tobacco
      smoke but was not sufficiently effective in protecting restaurant workers from
      occupational exposure to tobacco smoke.

PMID- 20688794
TI  - Attitudes to new smoking restrictions and second-hand smoke among young Finnish
      males.
AB  - AIMS: Relatively little is known about the attitudes of young people to
      restrictions on smoking in public places and to environmental second-hand smoke
      in housing estates. The objective was to explore the attitudes of young male
      adults after the new smoke-free legislation was implemented in Finland. METHODS:
      A survey of 1167 Finnish male military conscripts was performed. The main outcome
      variables were their attitudes to the new restrictions on smoking in public
      places and concerns about second-hand smoke in the home originating from their
      neighbours. RESULTS: Almost half of the youths (43.5%) reported that they
      supported the more restrictive smoking regulations, with 44.8% having a neutral
      view. Only 16.0% of the respondents were irritated about the second-hand smoke
      entering to their house from outside and 48.6% were not concerned about smoking
      in their neighbourhood. A total of 555 (47.6%) conscripts were current smokers.
      Current smokers were more often totally opposed to the legislation and had less
      negative views about the exposure to second-hand smoke than non-smokers. Strong
      nicotine dependence increased the feelings of anxiety and stigmatisation when the
      new restrictions were introduced. CONCLUSIONS: Finnish young men do accept new
      smoking restrictions. However, smoking with high nicotine dependence was
      surprisingly common among these young men and the negative attitude to the
      legislation can be traced to this group of smokers. The repulsion felt towards
      second-hand smoke by non-smokers represents an opportunity for public health
      initiatives to guarantee a smoke-free environment in public and private places.

PMID- 20688795
TI  - Evaluation of the long-term cost-effectiveness of insulin detemir compared with
      neutral protamine hagedorn insulin in patients with type 1 diabetes using a basal
      bolus regimen in Sweden.
AB  - AIMS: To evaluate the long-term clinical and economic outcomes associated with
      insulin detemir and neutral protamine hagedorn (NPH) insulin in combination with
      mealtime insulin aspart in patients with type 1 diabetes in Sweden, based on data
      from a two-year, multi-national, open-label, randomized, controlled trial.
      METHODS: Insulin detemir was associated with significant improvements in
      glycaemic control after 24 months (HbA1c 7.36% versus 7.58%, mean difference 
      0.22%, p = 0.022) and major hypoglycaemic events (69% risk reduction, p = 0.001)
      versus NPH. Patients treated with detemir gained less weight (1.7 versus 2.7 kg,
      P = 0.024). Based on these findings, a published and validated computer model
      (IMS CORE Diabetes Model) was used to estimate life-expectancy, quality-adjusted
      life expectancy and both direct medical costs and indirect costs. RESULTS: Basal
      bolus therapy with insulin detemir was projected to improve life expectancy by
      0.14 years (15.02 +/- 0.19 versus 14.88 +/- 0.18 years) and quality-adjusted life
      expectancy by 0.53 quality-adjusted life years (QALYs) versus NPH (8.35 +/- 0.11
      versus 7.82 +/- 0.10 QALYs). Improvements in QALYs were driven by avoided or
      delayed diabetes-related complications and fewer hypoglycaemic events. Direct
      medical costs over patient lifetimes were SEK 26,144 higher in the insulin
      detemir arm (SEK 995,025 +/- 19,580 versus 968,881 +/- 19,769), leading to an
      incremental cost-effectiveness ratio of SEK 49,757 per QALY gained. Capturing
      indirect costs led to insulin detemir being cost saving over patient lifetimes,
      by SEK 80,113, compared to NPH (SEK 2,959,909 +/- 64,727 versus 3,040,022 +/-
      62,317). CONCLUSIONS: Compared with NPH, insulin detemir is likely to be cost
      effective from a healthcare payer perspective and dominant from a societal
      perspective in patients with type 1 diabetes in Sweden.

PMID- 20688796
TI  - Widening the Psychiatric gaze: reflections on PsychoDoctor, depression, and
      recent transitions in japanese mental health care.
AB  - Japan has one of the world's highest rates of psychiatric institutionalization,
      and popular images of mental health care and public attitudes toward mental
      illness there have been stigmatized for decades. However, there are transitions
      underway that are reshaping the mental health care landscape as well as affecting
      public representations of mental illness. Those transitions include attempts to
      promote community-based care, move away from long-term hospitalization, reduce
      stigma, increase utilization of services, and bring clinical psychological
      services under the national health insurance umbrella. This article discusses one
      cultural representation in which those transitions are brought into relief: a
      2002 television series entitled PsychoDoctor that portrayed the clinical practice
      of a psychiatrist. The article analyzes the messages inherent in the series about
      the nature of mental illness, the everyday-ness of sufferers, and the expanded
      repertoire of treatments now available. In so doing, the article suggests that
      the efforts of progressive clinicians, pharmaceutical companies, and mental
      health activists to put forth new images of mental illness and mental health care
      are now having a degree of success in the arena of popular culture.

PMID- 20688797
TI  - Shared death: self, sociality and internet group suicide in Japan.
AB  - Existing models for understanding suicide fail to account for the distinctiveness
      of Internet group suicide, a recent phenomenon in Japan. Drawing from an
      ethnography of Internet suicide websites, two social commentaries in Japanese
      popular culture, and the work of developmental psychologist Philippe Rochat, I
      argue that participation in Internet suicide forums and even the act of Internet
      group suicide result from both a need for social connectedness and the fear of
      social rejection and isolation that this need engenders. These needs and fears
      are especially strong in the case of Japan, where the dominant cultural rhetoric
      ties selfhood closely to the social self that is the object of perception and
      experience by others. I show how such an understanding of Internet group suicide
      helps us to understand some of its basic characteristics, which are otherwise
      difficult to explain and which have puzzled the Japanese media and popular
      accounts: the "ordinariness" or casual nature of Internet group suicide, the wish
      for an easy or comfortable death, the wish to die with others, and the wish to
      "vanish." Internet group suicide sheds light on questions of Japanese selfhood in
      modernity and expands our understanding of suicide in Japan in general.

PMID- 20688798
TI  - Healers and psychiatrists: the transformation of mental health care in
      tajikistan.
AB  - This article examines the transformation of mental health care in Tajikistan from
      the time of Russian colonization of Central Asia until the most recent years of
      post-independence. It incorporates a review of published literature into the
      analysis of locally available reports, focus group discussions, interviews and
      oral histories collected between 2005 and 2008. Traditional healers play a
      significant role in contemporary Tajikistan, where mental health care provision
      is influenced by the legacy of Soviet psychiatry. Tajik mental health care may
      now be in a "dormant" phase, characterized by a widespread neglect of people with
      mental illnesses.

PMID- 20688799
TI  - Dental restorations for dinka and nuer refugees: a confluence of culture and
      healing.
AB  - The Harvard Trauma Questionnaire, Hopkins Symptom Checklist-25, and the Self
      reporting Questionnaire-24 were used to evaluate distress among 22 Dinka and Nuer
      refugees to the US before and after complete restoration of four to six lower
      front teeth that had been extracted during childhood in Sudan. Participants
      reported significant improvement in levels of distress following full restoration
      of missing teeth, including symptoms of PTSD. These results illustrate the value
      of incorporating community perspectives into the selection of health treatment
      options for newly arriving populations. But they also emphasize the unique
      situation faced by each refugee population as they embark on a wholly new
      cultural learning process.

PMID- 20688800
TI  - Treatment of depression in patients from ethnic minority groups in the
      Netherlands.
AB  - This article presents the results of a large efficacy study comparing different
      forms of therapy for major depressive disorder (MDD), including interpersonal
      psychotherapy (IPT) and pharmacotherapy. Patients were randomized to either IPT,
      IPT in combination with anti-depressant medication, IPT in combination with pill
      placebo or medication only. The primary outcome measure was the Hamilton Rating
      Scale for Depression (HAMD). Patients were treated for 12 to 16 weeks. Ratings
      were performed at baseline, after 6 weeks of treatment and at the end of
      treatment. Ethnic minority patients (EMP) had higher scores on the HAMD than non
      EMP for every rating period. However, the rate of improvement was the same for
      EMP and non-EMP. The higher mean scores of EMP on the HAMD could not be explained
      as solely due to higher scores on somatic items of the rating scales. The
      attrition rate in EMP (45.9%) was significantly higher than in non-EMP (24.4%),
      even in the structured treatment format studied. The results suggest that
      standard antidepressant therapy, be it medication, psychotherapy or both, may be
      effective for depressed minority patients but therapists should focus on
      enhancing adherence to treatment.

PMID- 20688801
TI  - Raves, psychosis, and spirit healing.
AB  - This paper reflects the intersection of three cultures: the rave (all night dance
      party and use of the drug, Ecstasy) culture; the ward culture of an inpatient
      psychiatric program for First Episode Psychosis; the spirit healing culture of
      the Philippines. All three intersected in Toronto, Canada in the mid 1990s, as
      illustrated by the clinical case of a 19-year-old university student who was
      hospitalized with symptoms of drug-induced psychosis. Her initial treatment was
      not successful and presented dilemmas for the treating staff. Transfer to a
      second psychiatric facility that permitted attendance at a traditional Filipino
      healing ceremony resulted in a cure, with no recurrence 10 years later. According
      to James Dow's 1986 formulation, the components of the key spiritual healing
      session paralleled the very elements the young woman had sought by participating
      in raves, an activity that was problematic because it led to family displeasure.
      Whereas attendance at a rave triggered illness, the healing session, sanctioned
      by her family and taking place in their midst, resulted in healing.

PMID- 20688803
TI  - Over-expression of paneth cell-derived anti-microbial peptides in the gut of
      patients with ankylosing spondylitis and subclinical intestinal inflammation.
AB  - OBJECTIVES: Subclinical gut inflammation has been demonstrated in patients with
      AS. Altered expression of paneth cell (PC) anti-microbial peptides have been
      reported in the inflamed ileum of patients with Crohn's disease (CD). Here, we
      investigated the expression of PC-derived peptides in subclinical gut
      inflammation in AS. METHODS: Multiple adjacent mucosal biopsies from terminal
      ileum were obtained from 25 patients with AS, 30 CD and 15 healthy controls
      (HCs). Expression of human alpha-defensin 5 (HD-5), phospholipase A2 (PLA2),
      lysozyme and SOX-9 molecules was assessed by quantitative Taqman RT-PCR on
      mucosal samples. Immunohistochemistry with anti-human HD-5 antibody and
      genotyping of relevant NOD2 mutations was also performed. RESULTS: HD-5, PLA2 and
      lysozyme transcript levels were strongly increased in AS and CD with similar
      degrees of intestinal inflammation when compared with normal controls.
      Immunohistochemical evaluation showed a normal number of PCs in both AS patients
      with chronic gut inflammation and CD patients with less-inflamed ileal samples.
      Conversely, CD patients with higher degree of gut inflammation had a reduced
      number of PCs and low expression levels of HD-5. CONCLUSION: In this study, we
      provide evidence that over-expression of PC-derived anti-microbial peptides
      occurs in the ileum of AS patients with subclinical gut inflammation, likely
      representing an important early alteration of the mucosal innate immune component
      and intestinal host defence in AS.

PMID- 20688804
TI  - Controlled follow-up study of physical and psychosocial functioning of
      adolescents with juvenile primary fibromyalgia syndrome.
AB  - OBJECTIVES: Currently, there are no prospective studies exploring the prognosis
      of patients with juvenile primary FM syndrome (JPFS) or their physical, emotional
      and social outcomes as they enter the early adult years. The primary objective of
      this study was to assess long-term outcomes of a paediatric sample of clinically
      referred JPFS patients and their matched healthy controls. METHODS: Participants
      were 48 youths (current mean age = 19 years) diagnosed with JPFS in childhood or
      adolescence and 43 healthy controls matched in age, gender and race. The average
      length of follow-up was 3.67 years (range 2-6 years). Participants completed
      online (web-based) self-report questionnaires about current pain and physical
      symptoms, health status, anxiety, depressive symptoms and current and past
      treatments. RESULTS: Results showed that 62.5% of participants in the JPFS group
      continued to experience widespread pain and 60.4% reported having all the
      cardinal features of FM syndrome (including widespread pain, poor sleep and
      fatigue) at follow-up. The JPFS group reported significantly lower scores on all
      measures of health status and physical functioning compared with healthy controls
      and significantly greater symptoms of anxiety and depression. CONCLUSION: The
      results of this controlled follow-up study demonstrate that symptoms of FM appear
      to be chronic in a majority of clinically referred JPFS patients and the
      associated physical and emotional impairment can also be persistent. Implications
      for treatment and the need for further prospective longitudinal studies are
      discussed.

PMID- 20688805
TI  - Four different patterns of fatigue in rheumatoid arthritis patients: results of a
      Q-sort study.
AB  - OBJECTIVES: Many patients with RA complain about fatigue. Whereas qualitative
      studies have covered the meaning of fatigue for RA patients, it was still unknown
      whether subgroups of patients could be distinguished. This study aimed to
      describe different perspectives on the experience of fatigue. METHODS:
      Participants were 30 outpatients with established controlled RA of the Medical
      Spectrum Twente, with a mean fatigue severity score of 4.67 (visual analogue
      scale 0-10). They evaluated 57 statements about fatigue according to Q
      methodology. Data were analysed with PCQ for Windows (Portland, OR, USA), using
      centroid factor analysis with varimax rotation (i.e. the participants but not the
      items of a scale are the variables). Factor scores of statements on the different
      dimensions were calculated to investigate which items are relevant when
      describing and distinguishing fatigue experiences. Demographic and clinical
      patient characteristics were collected to describe each of the dimensions that
      resulted from centroid factor analysis. RESULTS: After statistical and
      theoretical considerations, a four-factor structure of the data was obtained.
      Each factor represented a perspective on the experience of fatigue, shared by a
      certain group of patients. Physical, psychological and social patient
      characteristics seemed to be associated with those experiences. The factors were
      labelled as: 'Little impact of fatigue'; 'Good coping and bad sleep'; 'Search for
      balance'; and 'High distress'. CONCLUSIONS: Results indicated that fatigue
      experience is a complex phenomenon. Existing questionnaires to measure fatigue do
      not meet this complexity. Extensive research is warranted and new efforts to
      develop instruments that take into account all aspects of fatigue are indicated.

PMID- 20688806
TI  - Validation of the new paediatric criteria for the diagnosis of familial
      Mediterranean fever: data from a mixed population of 100 children from the French
      reference centre for auto-inflammatory disorders.
AB  - OBJECTIVE: We aimed to validate the new paediatric criteria for diagnosis of FMF
      in a mixed population of 100 French patients. METHODS: The study group included
      100 FMF children from the French reference centre for auto-inflammatory
      disorders. A control group of 40 patients with unexplained recurrent fever was
      reviewed in parallel. Both groups of patients were assessed for both the Tel
      Hashomer and the new paediatric criteria published by Yalcinkaya et al. RESULTS:
      Comparison of Tel Hashomer vs Yalcinkaya's criteria in both groups gave a
      sensitivity of 99 vs 100%, a specificity of 45 vs 50%, a positive predictive
      value (PPV) of 81.8 vs 83.3% and a negative predictive value (NPV) of 94.7 vs
      100%. However, when we used at least three Yalcinkaya's criteria we obtained a
      sensitivity of 77% and a specificity of 95% with a PPV of 97.3% and an NPV of
      62.3%. The number of mutations in the MEFV gene did not modify results for both
      sets of criteria. CONCLUSION: The new paediatric Turkish criteria did not make a
      better contribution to FMF diagnosis than the Tel Hashomer criteria in our mixed
      population of French children while using an appropriate control group. However,
      if needed, they can be applied using at least three criteria, which slightly
      decreases their sensitivity but markedly increases their specificity.

PMID- 20688807
TI  - Bevacizumab.

PMID- 20688808
TI  - Lineage-specific variation in intensity of natural selection in mammals.
AB  - The molecular clock hypothesis states that protein-coding genes evolve at an
      approximately constant rate. However, this is only expected to be true as long as
      the function and the tertiary structure of the molecule remain unaltered. An
      important implication of this statement is that significant deviations in the
      rate of evolution of a gene with respect to the species clock are likely to
      reflect functional and/or structural alterations. Here, we present a method to
      identify such deviations and apply it to a data set of 2,929 high-quality coding
      sequence alignments corresponding to one-to-one orthologous genes from six
      mammalian species--human, macaque, mouse, rat, cow, and dog. Deviated branches
      are defined as those that present significant alterations in both the rate of
      nonsynonymous substitutions (dN) and the selective pressure (dN/dS). Strikingly,
      we find that as many as 24.5% of the genes show branch-specific deviations in dN
      and dN/dS, though this is a relatively well-conserved set of genes. Around half
      of these genes show branch-specific acceleration of evolutionary rates. Positive
      selection (PS) tests based on divergence data only identify 17.7% of the
      accelerated branches. Failure to identify PS in accelerated branches with an
      excess of radical amino acid replacements suggests that these tests are
      conservative. Interestingly, genes with accelerated branches are significantly
      enriched in neural proteins, indicating that this type of protein might play a
      more important role than previously thought in species diversification, although
      they are generally not detected by PS tests. We discuss in detail several
      examples of genes that show lineage-specific evolutionary rate acceleration and
      are involved in synaptic transmission, chemosensory perception, and
      ubiquitination.

PMID- 20688809
TI  - Oligodendrocytes are damaged by neuromyelitis optica immunoglobulin G via
      astrocyte injury.
AB  - Devic's neuromyelitis optica is an inflammatory demyelinating disorder normally
      restricted to the optic nerves and spinal cord. Since the identification of a
      specific autoantibody directed against aquaporin 4, neuromyelitis optica
      immunoglobulin G/aquaporin 4 antibody, neuromyelitis optica has been considered
      an entity distinct from multiple sclerosis. Recent findings indicate that the
      neuromyelitis optica-immunoglobulin G/aquaporin 4 antibody has a pathogenic role
      through complement-dependent astrocyte toxicity. However, the link with
      demyelination remains elusive. Autoantibodies can act as receptor
      agonists/antagonists or alter antigen density in their target cells. We
      hypothesized that the neuromyelitis optica-immunoglobulin G/aquaporin 4 antibody
      impairs astrocytic function and secondarily leads to demyelination. Rat
      astrocytes and oligodendrocytes from primary cultures and rat optic nerves were
      exposed long-term (24 h) to immunoglobulin G in the absence of complement.
      Immunoglobulin G was purified from the serum of patients with neuromyelitis
      optica who were either neuromyelitis optica-immunoglobulin G/aquaporin 4 antibody
      positive or negative, as well as from healthy controls. Flow cytometry analysis
      showed a reduction of membrane aquaporin 4 and glutamate transporter type 1 on
      astrocytes following contact with immunoglobulin G purified from neuromyelitis
      optica-immunoglobulin G/aquaporin 4 antibody positive serum only. The activity of
      glutamine synthetase, an astrocyte enzyme converting glutamate into glutamine,
      decreased in parallel, indicating astrocyte dysfunction. Treatment also reduced
      oligodendrocytic cell processes and approximately 30% oligodendrocytes died. This
      deleterious effect was confirmed ex vivo; exposed optic nerves showed reduction
      of myelin basic protein. Immunoglobulin G from neuromyelitis optica
      immunoglobulin G/aquaporin 4 antibody seronegative patients and from healthy
      controls had no similar effect. Neuromyelitis optica-immunoglobulin G/aquaporin 4
      antibody did not directly injure oligodendrocytes cultured without astrocytes. A
      toxic bystander effect of astrocytes damaged by neuromyelitis optica
      immunoglobulin G/aquaporin 4 antibody on oligodendrocytes was identified.
      Progressive accumulation of glutamate in the culture medium of neuromyelitis
      optica-immunoglobulin G/aquaporin 4-antibody-treated glial cells supported the
      hypothesis of a glutamate-mediated excitotoxic death of oligodendrocytes in our
      models. Moreover, co-treatment of glial cultures with neuromyelitis optica
      immunoglobulin G/aquaporin 4 antibody and d+2-amino-5-phosphonopentanoic acid, a
      competitive antagonist at the N-methyl-d-aspartate/glutamate receptor, partially
      protected oligodendrocytes. Co-immunolabelling of oligodendrocyte markers and
      neuromyelitis optica-immunoglobulin G/aquaporin 4 antibody showed that astrocytic
      positive processes were in close contact with oligodendrocytes and myelin in rat
      optic nerves and spinal cord, but far less so in other parts of the central
      nervous system. This suggests a bystander effect of neuromyelitis optica
      immunoglobulin G-damaged astrocytes on oligodendrocytes in the nervous tissues
      affected by neuromyelitis optica. In conclusion, in these cell culture models we
      found a direct, complement-independent effect of neuromyelitis optica
      immunoglobulin G/aquaporin 4 antibody on astrocytes, with secondary damage to
      oligodendrocytes possibly resulting from glutamate-mediated excitotoxicity. These
      mechanisms could add to the complement-induced damage, particularly the
      demyelination, seen in vivo.

PMID- 20688810
TI  - Recovery of upper-limb function due to enhanced use-dependent plasticity in
      chronic stroke patients.
AB  - Patients with chronic stroke often show increased flexor hypertonia in their
      affected upper limbs. Although an intervention strategy targeting the extensors
      of the affected upper limb might thus be expected to have benefits for functional
      recovery, conventional repetitive motor training has limited clinical utility.
      Recent studies have shown that repetitive transcranial magnetic stimulation could
      induce motor recovery. The present study tested whether 5 Hz repetitive
      transcranial magnetic stimulation of the upper-limb area of the primary motor
      cortex, combined with extensor motor training, had a greater effect on motor
      recovery than either intervention alone in stroke hemiparesis. Nine patients with
      chronic subcortical stroke and nine age-matched healthy subjects completed the
      crossover study. In separate sessions, we examined the single intervention effect
      of repetitive wrist and finger extension exercises aided by neuromuscular
      stimulation, the single intervention effect of 5 Hz repetitive transcranial
      magnetic stimulation and the combined effect of the two interventions. The motor
      functions were evaluated behaviourally in patients (Experiment 1) and
      electrophysiologically in healthy subjects (Experiment 2), both before and after
      the intervention. In addition, we tested the long-term effect by repeating the
      combined interventions 12 times in patients (Experiment 3). The motor functions
      were measured again 2 weeks after the end of the repetitive intervention period.
      In Experiment 1, the combined intervention, but neither of the single
      interventions, resulted in an improvement of extensor movement (P < 0.0001) and
      grip power (P < 0.05), along with a reduction of flexor hypertonia (P < 0.01), in
      their paretic upper limbs. In Experiment 2, only the combined intervention
      resulted in selective plastic changes of cortico-spinal excitability (P < 0.01),
      motor threshold (P < 0.001) and silent period (P < 0.01) for the extensors. In
      Experiment 3, we also confirmed long-term beneficial effects of the combined
      intervention in patients. These findings indicate that combining motor training
      with repetitive transcranial magnetic stimulation can facilitate use-dependent
      plasticity and achieve functional recovery of motor impairments that cannot be
      attained by either intervention alone. This method could be a powerful
      rehabilitative approach for patients with hemiparetic stroke.

PMID- 20688811
TI  - Cortical reorganization in dyslexic children after phonological training:
      evidence from early evoked potentials.
AB  - Brain plasticity was investigated in 14 Italian children affected by
      developmental dyslexia after 6 months of phonological training. The means used to
      measure language reorganization was the recognition potential, an early wave,
      also called N150, elicited by automatic word recognition. This component peaks
      over the left temporo-occipital cortex and its amplitude depends on linguistic
      expertise. N150 elicited by written words was measured both in dyslexic children
      before and after training and in a sample of matched normal readers during
      phonological, semantic and orthographic tasks. After training, dyslexic children
      increased their reading speed. Normal readers showed a typical left posterior
      N150, whereas in dyslexic children it was equally distributed across hemispheres
      before and shifted to left posterior sites after training. In addition,
      dyslexics' left posterior N150 asymmetry on the phonological task after training
      was significantly correlated with reading speed improvement, that is, those
      children who showed the greatest left shift in phonological N150 also had the
      greatest reading speed improvement. Source localization of the N150 component was
      made with both the Standard Low Resolution Electromagnetic Tomography software
      and the classical dipole analysis method termed Brain Electrical Source Analysis.
      The N150 generator lies in the left occipito-temporal cortex (Brodmann areas 39,
      37 and 19) in good readers, but in right homologous areas in dyslexic children
      before training. After the treatment, the dyslexics' main N150 generator shifted
      to the left occipito-inferotemporal cortex (namely Brodmann areas 37 and 19) with
      small differences between tasks. The two source location methods provided
      consistent, converging solutions. Results add to the current literature on the
      phonological hypothesis of dyslexia by showing hemispheric reorganization of
      linguistic networks at the level of early word recognition potential.
      Furthermore, the present work is the first to investigate brain reorganization in
      a regular/transparent language like Italian.

PMID- 20688812
TI  - Neuronal networks in children with continuous spikes and waves during slow sleep.
AB  - Epileptic encephalopathy with continuous spikes and waves during slow sleep is an
      age-related disorder characterized by the presence of interictal epileptiform
      discharges during at least >85% of sleep and cognitive deficits associated with
      this electroencephalography pattern. The pathophysiological mechanisms of
      continuous spikes and waves during slow sleep and neuropsychological deficits
      associated with this condition are still poorly understood. Here, we investigated
      the haemodynamic changes associated with epileptic activity using simultaneous
      acquisitions of electroencephalography and functional magnetic resonance imaging
      in 12 children with symptomatic and cryptogenic continuous spikes and waves
      during slow sleep. We compared the results of magnetic resonance to electric
      source analysis carried out using a distributed linear inverse solution at two
      time points of the averaged epileptic spike. All patients demonstrated highly
      significant spike-related positive (activations) and negative (deactivations)
      blood oxygenation-level-dependent changes (P < 0.05, family-wise error
      corrected). The activations involved bilateral perisylvian region and cingulate
      gyrus in all cases, bilateral frontal cortex in five, bilateral parietal cortex
      in one and thalamus in five cases. Electrical source analysis demonstrated a
      similar involvement of the perisylvian brain regions in all patients, independent
      of the area of spike generation. The spike-related deactivations were found in
      structures of the default mode network (precuneus, parietal cortex and medial
      frontal cortex) in all patients and in caudate nucleus in four. Group analyses
      emphasized the described individual differences. Despite aetiological
      heterogeneity, patients with continuous spikes and waves during slow sleep were
      characterized by activation of the similar neuronal network: perisylvian region,
      insula and cingulate gyrus. Comparison with the electrical source analysis
      results suggests that the activations correspond to both initiation and
      propagation pathways. The deactivations in structures of the default mode network
      are consistent with the concept of epileptiform activity impacting on normal
      brain function by inducing repetitive interruptions of neurophysiological
      function.

PMID- 20688813
TI  - Adeno-associated viral vector-induced overexpression of neuropeptide Y Y2
      receptors in the hippocampus suppresses seizures.
AB  - Gene therapy using recombinant adeno-associated viral vectors overexpressing
      neuropeptide Y in the hippocampus exerts seizure-suppressant effects in rodent
      epilepsy models and is currently considered for clinical application in patients
      with intractable mesial temporal lobe epilepsy. Seizure suppression by
      neuropeptide Y in the hippocampus is predominantly mediated by Y2 receptors,
      which, together with neuropeptide Y, are upregulated after seizures as a
      compensatory mechanism. To explore whether such upregulation could prevent
      seizures, we overexpressed Y2 receptors in the hippocampus using recombinant
      adeno-associated viral vectors. In two temporal lobe epilepsy models, electrical
      kindling and kainate-induced seizures, vector-based transduction of Y2 receptor
      complementary DNA in the hippocampus of adult rats exerted seizure-suppressant
      effects. Simultaneous overexpression of Y2 and neuropeptide Y had a more
      pronounced seizure-suppressant effect. These results demonstrate that
      overexpression of Y2 receptors (alone or in combination with neuropeptide Y)
      could be an alternative strategy for epilepsy treatment.

PMID- 20688814
TI  - Sequential relationships between grey matter and white matter atrophy and brain
      metabolic abnormalities in early Alzheimer's disease.
AB  - Hippocampal atrophy, posterior cingulate and frontal glucose hypometabolism, and
      white-matter tract disruption are well described early macroscopic events in
      Alzheimer's disease. The relationships between these three types of alterations
      have been documented in previous studies, but their chronology still remains to
      be established. The present study used multi-modal fluorodeoxyglucose-positron
      emission tomography and magnetic resonance imaging longitudinal data to address
      this question in patients with amnestic mild cognitive impairment. We found
      unidirectional, specific sequential relationships between: (i) baseline
      hippocampal atrophy and both cingulum bundle (r = 0.70; P = 3 * 10-3) and
      uncinate fasciculus (r = 0.75; P = 7 * 10-4) rate of atrophy; (ii) baseline
      cingulum bundle atrophy and rate of decline of posterior (r = 0.72; P = 2 * 10
      3); and anterior (r = 0.74; P = 1 * 10-3) cingulate metabolism; and (iii)
      baseline uncinate white matter atrophy and subgenual metabolism rate of change (r
      = 0.65; P = 6 * 10-3). Baseline local grey matter atrophy was not found to
      contribute to hypometabolism progression within the posterior and anterior
      cingulate as well as subgenual cortices. These findings suggest that hippocampal
      atrophy progressively leads to disruption of the cingulum bundle and uncinate
      fasciculus, which in turn leads to glucose hypometabolism of the cingulate and
      subgenual cortices, respectively. This study reinforces the relevance of remote
      mechanisms above local interactions to account for the pattern of metabolic brain
      alteration observed in amnestic mild cognitive impairment, and provides new
      avenues to assess the sequence of events in complex diseases characterized by
      multiple manifestations.

PMID- 20688815
TI  - Visual working memory deficits in patients with Parkinson's disease are due to
      both reduced storage capacity and impaired ability to filter out irrelevant
      information.
AB  - Given that Parkinson's disease broadly affects frontostriatal circuitry, it is
      not surprising that the disorder is associated with a reduction of working
      memory. We tested whether this reduction is due to diminished storage capacity or
      impaired ability to exclude task-irrelevant items. Twenty-one medication
      withdrawn patients and 28 age-matched control subjects performed a visuospatial
      memory task while their electroencephalograms were recorded. The task required
      them to remember the orientations of red rectangles within the half of the screen
      that was cued while ignoring all green rectangles. Behavioural and
      electroencephalogram measures indicated that patients with Parkinson's disease
      were impaired at filtering out distracters, and that they were able to hold fewer
      items in memory than control subjects. The results support recent suggestions
      that the basal ganglia help control access to working memory.

PMID- 20688816
TI  - Structural studies of cord factors from Mycobacterium simiae related to the
      capacity for tumour necrosis factor alpha (alpha-TNF) induction.
AB  - The structure of cord factor was studied in several strains of Mycobacterium
      simiae, including 'habana' TMC 5135, considered as highly immunogenic in
      experimental tuberculosis and leprosy. The mycolic acids liberated from cord
      factor were identified in all cases as alpha'-, alpha- and keto-mycolates.
      According to the general NMR and MS data, alpha'-mycolates were mono-unsaturated
      and contained from 64 to 68 carbon atoms, whereas alpha-mycolates mainly
      presented two 2,3-disubstituted cyclopropane rings and a chain length of 80-91
      carbon atoms; keto-mycolates mostly contained one cyclopropane ring and 85-91
      carbon atoms. Taking into account the (1)H-NMR results, strains varied in the
      ratio of the different mycolates, and the high levels of keto-mycolates found in
      the cord factors of TMC 5135 and ATCC 25275(T) stood out. Notably, MS revealed
      that the odd carbon number series of alpha-mycolates (C87-C89) predominated in
      the cord factor of TMC 5135, in contrast to the remaining studied strains, in
      which the even (C84-C86) and odd carbon number series appeared more equal. The
      fine structural differences detected among the cord factors studied did not seem
      to be relevant to the general capacity of these molecules to induce the secretion
      of tumour necrosis factor alpha, as the cord factors from several strains of M.
      simiae (TMC 5135, IPK-342 and ATCC 25275(T)) induced similar amounts of this
      cytokine in RAW 264.7 cells.

PMID- 20688817
TI  - Mapping the epithelial-cell-binding domain of the Aggregatibacter
      actinomycetemcomitans autotransporter adhesin Aae.
AB  - The Gram-negative periodontopathogen Aggregatibacter actinomycetemcomitans (Aa)
      binds selectively to buccal epithelial cells (BECs) of human and Old World
      primates by means of the outer-membrane autotransporter protein Aae. We
      speculated that the exposed N-terminal portion of the passenger domain of Aae
      would mediate binding to BECs. By using a series of plasmids that express full
      length or truncated Aae proteins in Escherichia coli, we found that the BEC
      binding domain of Aae was located in the N-terminal surface-exposed region of the
      protein, specifically in the region spanning amino acids 201-284 just upstream of
      the repeat region within the passenger domain. Peptides corresponding to amino
      acids 201-221, 222-238 and 201-240 were synthesized and tested for their ability
      to reduce Aae-mediated binding to BECs based on results obtained with truncated
      Aae proteins expressed in E. coli. BEC-binding of E. coli expressing Aae was
      reduced by as much as 50 % by pre-treatment of BECs with a 40-mer peptide (201
      240; P40). Aae was also shown to mediate binding to cultured human epithelial
      keratinocytes (TW2.6), OBA9 and TERT, and endothelial (HUVEC) cells. Pre
      treatment of epithelial cells with P40 resulted in a dose-dependent reduction in
      binding and reduced the binding of both full-length and truncated Aae proteins
      expressed in E. coli, as well as Aae expressed in Aa. Fluorescently labelled P40
      peptides reacted in a dose-dependent manner with BEC receptors. We propose that
      these proof-of-principle experiments demonstrate that peptides can be designed to
      interfere with Aa binding mediated by host-cell receptors specific for Aae
      adhesins.

PMID- 20688818
TI  - Mycobacterium marinum MMAR_2380, a predicted transmembrane acyltransferase, is
      essential for the presence of the mannose cap on lipoarabinomannan.
AB  - Lipoarabinomannan (LAM) is a major glycolipid in the mycobacterial cell envelope.
      LAM consists of a mannosylphosphatidylinositol (MPI) anchor, a mannan core and a
      branched arabinan domain. The termini of the arabinan branches can become
      substituted with one to three alpha(1->2)-linked mannosyl residues, the mannose
      cap, producing ManLAM. ManLAM has been associated with a range of different
      immunomodulatory properties of Mycobacterium tuberculosis during infection of the
      host. In some of these effects, the presence of the mannose cap on ManLAM appears
      to be crucial for its activity. So far, in the biosynthesis of the mannose cap on
      ManLAM, two enzymes have been reported to be involved: a mannosyltransferase that
      adds the first mannosyl residue of the mannose caps to the arabinan domain of
      LAM, and another mannosyltransferase that elongates the mannose cap up to three
      mannosyl residues. Here, we report that a third gene is involved, MMAR_2380,
      which is the Mycobacterium marinum orthologue of Rv1565c. MMAR_2380 encodes a
      predicted transmembrane acyltransferase. In M. marinum DeltaMMAR_2380, the LAM
      arabinan domain is still intact, but the mutant LAM lacks the mannose cap.
      Additional effects of mutation of MMAR_2380 on LAM were observed: a higher degree
      of branching of both the arabinan domain and the mannan core, and a decreased
      incorporation of [1,2-(14)C]acetate into the acyl chains in mutant LAM as
      compared with the wild-type form. This latter effect was also observed for
      related lipoglycans, i.e. lipomannan (LM) and phosphatidylinositol mannosides
      (PIMs). Furthermore, the mutant strain showed increased aggregation in liquid
      cultures as compared with the wild-type strain. All phenotypic traits of M.
      marinum DeltaMMAR_2380, the deficiency in the mannose cap on LAM and changes at
      the cell surface, could be reversed by complementing the mutant strain with
      MMAR_2380. Strikingly, membrane preparations of the mutant strain still showed
      enzymic activity for the arabinan mannose-capping mannosyltransferase similar to
      that of the wild-type strain. Although the exact function of MMAR_2380 remains
      unknown, we show that the protein is essential for the presence of a mannose cap
      on LAM.

PMID- 20688819
TI  - ClgR regulation of chaperone and protease systems is essential for Mycobacterium
      tuberculosis parasitism of the macrophage.
AB  - Chaperone and protease systems play essential roles in cellular homeostasis and
      have vital functions in controlling the abundance of specific cellular proteins
      involved in processes such as transcription, replication, metabolism and
      virulence. Bacteria have evolved accurate regulatory systems to control the
      expression and function of chaperones and potentially destructive proteases.
      Here, we have used a combination of transcriptomics, proteomics and targeted
      mutagenesis to reveal that the clp gene regulator (ClgR) of Mycobacterium
      tuberculosis activates the transcription of at least ten genes, including four
      that encode protease systems (ClpP1/C, ClpP2/C, PtrB and HtrA-like protease
      Rv1043c) and three that encode chaperones (Acr2, ClpB and the chaperonin Rv3269).
      Thus, M. tuberculosis ClgR controls a larger network of protein homeostatic and
      regulatory systems than ClgR in any other bacterium studied to date. We
      demonstrate that ClgR-regulated transcriptional activation of these systems is
      essential for M. tuberculosis to replicate in macrophages. Furthermore, we
      observe that this defect is manifest early in infection, as M. tuberculosis
      lacking ClgR is deficient in the ability to control phagosome pH 1&emsp14;h post
      phagocytosis.

PMID- 20688820
TI  - Molecular pathogenesis of Listeria monocytogenes in the alternative model host
      Galleria mellonella.
AB  - Larvae of Galleria mellonella, the greater wax moth, provide an alternative
      infection model for many human pathogens as they are amenable to use at elevated
      incubation temperatures (37&emsp14; degrees C). This study and a parallel study
      by Mukherjee et al. [Mukherjee, K., Altincicek, B., Hain, T., Domann, E.,
      Vilcinskas, A. & Chakraborty, T. (2010). Appl Environ Microbiol 76, 310-317]
      establish this insect host as an appropriate model to investigate the
      pathogenesis of Listeria species. In this study we show that inoculation with
      Listeria monocytogenes initiates a dynamic infection in G. mellonella and that
      production of the cytolysin listeriolysin O (LLO) is necessary for toxicity and
      bacterial growth. Production of LLO by the non-pathogenic species Lactococcus
      lactis is sufficient to induce mortality in the insect model. We employed real
      time bioluminescence imaging to examine the dynamics of listerial growth and
      virulence gene expression in the G. mellonella model. Analysis of lux promoter
      fusions demonstrated significant induction of virulence gene expression upon
      introduction of the pathogen into insects at both 30 and 37&emsp14; degrees C.
      The host response to listerial infection was examined which demonstrated that
      haemocyte destruction accompanies L. monocytogenes pathogenesis and is preceded
      by activation of the phenoloxidase system. Furthermore, we demonstrate that
      Listeria innocua is pathogenic to G. mellonella through a persistence mechanism
      that implicates an alternative mechanism for pathogenicity in this model.

PMID- 20688821
TI  - A ToxR-dependent role for the putative phosphoporin VCA1008 in bile salt
      resistance in Vibrio cholerae El Tor N16961.
AB  - The putative phosphoporin encoded by vca1008 of Vibrio cholerae O1 is expressed
      in vivo during infection and is essential for the intestinal colonization of
      infant mice. In vitro, its expression is induced under inorganic phosphate (P(i))
      limitation in a PhoB/R-dependent manner. In this work we demonstrated that
      VCA1008 has a strain-specific role in the physiology and pathogenicity of V.
      cholerae O1. Disruption of vca1008 led to a growth defect, an inability to
      colonize and a high susceptibility to sodium deoxycholate (DOC; the major bile
      compound) in the El Tor biotype strain N16961, but did not affect the classical
      strain O395 in the same way. Furthermore, vca1008 promoter activity was higher in
      N16961 cells grown under a low P(i) supply in the presence of DOC than in the
      absence of the detergent. In the P(i)-limited cells, vca1008 was positively
      regulated by PhoB, but when DOC was added to the medium, it negatively affected
      the PhoB-mediated activation of the gene, and enhanced vca1008 expression in a
      ToxR-dependent manner. These findings reveal for the first time a complex strain
      specific interplay between ToxR and PhoB/R systems to control porin genes, as
      well as the influence of DOC on the expression of PhoB- and ToxR-regulated genes
      and pathogenesis in pandemic strains of V. cholerae.

PMID- 20688822
TI  - Interaction of colicin E7 with the major coat protein (g8p) may confer limited
      protection on colicinogenic Escherichia coli against M13 bacteriophage infection.
AB  - Colicin release provides producer strains with a competitive advantage under
      certain circumstances. We found that propagation of M13 bacteriophage in cells
      producing colicin E7 is impaired, without alteration in the efficiency of
      bacteriophage adsorption, as compared with non-producing cells. In contrast to
      the protective effect of the colicin against M13 bacteriophage infection, the
      endogenously expressed colicin does not confer limited protection against
      transfection with M13 bacteriophage DNA. Furthermore, it was found that the
      translocation-receptor-binding domain and toxicity domain of the colicin are able
      to interact with the M13 major coat protein, g8p, during bacteriophage infection.
      Based on these observations, we propose that interaction between colicin E7 and
      g8p during infection interferes with g8p depolymerizing into the cytoplasmic
      membrane during bacteriophage DNA penetration, thus resulting in the limited
      protection against M13 bacteriophage infection.

PMID- 20688823
TI  - Reproduction without sex: conidiation in the filamentous fungus Trichoderma.
AB  - Trichoderma spp. have served as models for asexual reproduction in filamentous
      fungi for over 50 years. Physical stimuli, such as light exposure and mechanical
      injury to the mycelium, trigger conidiation; however, conidiogenesis itself is a
      holistic response determined by the cell's metabolic state, as influenced by the
      environment and endogenous biological rhythms. Key environmental parameters are
      the carbon and nitrogen status and the C : N ratio, the ambient pH and the level
      of calcium ions. Recent advances in our understanding of the molecular biology of
      this fungus have revealed a conserved mechanism of environmental perception
      through the White Collar orthologues BLR-1 and BLR-2. Also implicated in the
      molecular regulation are the PacC pathways and the conidial regulator VELVET.
      Signal transduction cascades which link environmental signals to physiological
      outputs have also been revealed.

PMID- 20688824
TI  - Deletion of the Candida albicans histidine kinase gene CHK1 improves recognition
      by phagocytes through an increased exposure of cell wall beta-1,3-glucans.
AB  - The pathogenic fungus Candida albicans is able to cover its most potent
      proinflammatory cell wall molecules, the beta-glucans, underneath a dense mannan
      layer, so that the pathogen becomes partly invisible for immune cells such as
      phagocytes. As the C. albicans histidine kinases Chk1p, Cos1p and CaSln1p had
      been reported to be involved in virulence and cell wall biosynthesis, we
      investigated whether deletion of the respective genes influences the activity of
      phagocytes against C. albicans. We found that among all histidine kinase genes,
      CHK1 plays a prominent role in phagocyte activation. Uptake of the deletion
      mutant Deltachk1 as well as the acidification of Deltachk1-carrying phagosomes
      was significantly increased compared with the parental strain. These improved
      activities could be correlated with an enhanced accessibility of the mutant beta
      1,3-glucans for immunolabelling. In addition, any inhibition of beta-1,3-glucan
      mediated phagocytosis resulted in a reduced uptake of Deltachk1, while ingestion
      of the parental strain was hardly affected. Moreover, deletion of CHK1 caused an
      enhanced release of interleukins 6 and 10, indicating a stronger activation of
      the beta-1,3-glucan receptor dectin-1. In conclusion, the Chk1p protein is likely
      to be involved in masking beta-1,3-glucans from immune recognition. As there are
      no homologues of fungal histidine kinases in mammals, Chk1p has to be considered
      as a promising target for new antifungal agents.

PMID- 20688825
TI  - Genes required for the synthesis of heptose-containing oligosaccharide outer core
      extensions in Haemophilus influenzae lipopolysaccharide.
AB  - Heptose-containing oligosaccharides (OSs) are found in the outer core of the
      lipopolysaccharide (LPS) of a subset of non-typable Haemophilus influenzae (NTHi)
      strains. Candidate genes for the addition of either l-glycero-d-manno-heptose (ld
      Hep) or d-glycero-d-manno-heptose (dd-Hep) and subsequent hexose sugars to these
      OSs have been identified from the recently completed genome sequences available
      for NTHi strains. losA1/losB1 and losA2/losB2 are two sets of related genes in
      which losA has homology to genes encoding glycosyltransferases and losB to genes
      encoding heptosyltransferases. Each set of genes is variably present across NTHi
      strains and is located in a region of the genome with an alternative gene
      organization between strains that contributes to LPS heterogeneity. Dependent
      upon the strain background, the LPS phenotype, structure and serum resistance of
      strains mutated in these genes were altered when compared with the relevant
      parent strain. Our studies confirm that losB1 and losB2 usually encode dd
      heptosyl- and ld-heptosyl transferases, respectively, and that losA1 and losA2
      encode glycosyltransferases that play a role in OS extensions of NTHi LPS.

PMID- 20688826
TI  - Roles of the twin-arginine translocase and associated chaperones in the
      biogenesis of the electron transport chains of the human pathogen Campylobacter
      jejuni.
AB  - The zoonotic pathogen Campylobacter jejuni NCTC 11168 uses a complex set of
      electron transport chains to ensure growth with a variety of electron donors and
      alternative electron acceptors, some of which are known to be important for host
      colonization. Many of the key redox proteins essential for electron transfer in
      this bacterium have N-terminal twin-arginine translocase (TAT) signal sequences
      that ensure their transport across the cytoplasmic membrane in a folded state. By
      comparisons of 2D gels of periplasmic extracts, gene fusions and specific enzyme
      assays in wild-type, tatC mutant and complemented strains, we experimentally
      verified the TAT dependence of 10 proteins with an N-terminal twin-arginine
      motif. NrfH, which has a TAT-like motif (LRRKILK), was functional in nitrite
      reduction in a tatC mutant, and was correctly rejected as a TAT substrate by the
      tatfind and TatP prediction programs. However, the hydrogenase subunit HydA is
      also rejected by tatfind, but was shown to be TAT-dependent experimentally. The
      YedY homologue Cj0379 is the only TAT translocated molybdoenzyme of unknown
      function in C. jejuni; we show that a cj0379c mutant is deficient in chicken
      colonization and has a nitrosative stress phenotype, suggestive of a possible
      role for Cj0379 in the reduction of reactive nitrogen species in the periplasm.
      Only two potential TAT chaperones, NapD and Cj1514, are encoded in the genome.
      Surprisingly, despite homology to TorD, Cj1514 was shown to be specifically
      required for the activity of formate dehydrogenase, not trimethylamine N-oxide
      reductase, and was designated FdhM.

PMID- 20688827
TI  - Unexpected consequences of administering bacteriocinogenic probiotic strains for
      Salmonella populations, revealed by an in vitro colonic model of the child gut.
AB  - New biological strategies for the treatment of Salmonella infection are needed in
      response to the increase in antibiotic-resistant strains. Escherichia coli L1000
      and Bifidobacterium thermophilum RBL67 were previously shown to produce
      antimicrobial proteinaceous compounds (microcin B17 and thermophilicin B67,
      respectively) active in vitro against a panel of Salmonella strains recently
      isolated from clinical cases in Switzerland. In this study, two three-stage
      intestinal continuous fermentation models of Salmonella colonization inoculated
      with immobilized faeces of a two-year-old child were implemented to study the
      effects of the two bacteriocinogenic strains compared with a bacteriocin-negative
      mutant of strain L1000 on Salmonella growth, as well as gut microbiota
      composition and metabolic activity. Immobilized E. coli L1000 added to the
      proximal colon reactor showed a low colonization, and developed preferentially in
      the distal colon reactor independent of the presence of genetic determinants for
      microcin B17 production. Surprisingly, E. coli L1000 addition strongly stimulated
      Salmonella growth in all three reactors. In contrast, B. thermophilum RBL67 added
      in a second phase stabilized at high levels in all reactors, but could not
      inhibit Salmonella already present at a high level (>10(7) c.f.u. ml(-1)) when
      the probiotic was added. Inulin added at the end of fermentation induced a strong
      bifidogenic effect in all three colon reactors and a significant increase of
      Salmonella counts in the distal colon reactor. Our data show that under the
      simulated child colonic conditions, the microcin B17 production phenotype does
      not correlate with inhibition of Salmonella but leads to a better colonization of
      E. coli L1000 in the distal colon reactor. We conclude that in vitro models with
      complex and complete gut microbiota are required to accurately assess the
      potential and efficacy of probiotics with respect to Salmonella colonization in
      the gut.

PMID- 20688828
TI  - The rkpU gene of Sinorhizobium fredii HH103 is required for bacterial K-antigen
      polysaccharide production and for efficient nodulation with soybean but not with
      cowpea.
AB  - In this work, the role of the rkpU and rkpJ genes in the production of the K
      antigen polysaccharides (KPS) and in the symbiotic capacity of Sinorhizobium
      fredii HH103, a broad host-range rhizobial strain able to nodulate soybean and
      many other legumes, was studied. The rkpJ- and rkpU-encoded products are
      orthologous to Escherichia coli proteins involved in capsule export. S. fredii
      HH103 mutant derivatives were contructed in both genes. To our knowledge, this is
      the first time that the role of rkpU in KPS production has been studied in
      rhizobia. Both rkpJ and rkpU mutants were unable to produce KPS. The rkpU
      derivative also showed alterations in its lipopolysaccharide (LPS). Neither KPS
      production nor rkpJ and rkpU expression was affected by the presence of the
      flavonoid genistein. Soybean (Glycine max) plants inoculated with the S. fredii
      HH103 rkpU and rkpJ mutants showed reduced nodulation and clear symptoms of
      nitrogen starvation. However, neither the rkpJ nor the rkpU mutants were
      significantly impaired in their symbiotic interaction with cowpea (Vigna
      unguiculata). Thus, we demonstrate for the first time to our knowledge the
      involvement of the rkpU gene in rhizobial KPS production and also show that the
      symbiotic relevance of the S. fredii HH103 KPS depends on the specific bacterium
      legume interaction.

PMID- 20688829
TI  - Activation of the latent PlcR regulon in Bacillus anthracis.
AB  - Many genes in Bacillus cereus and Bacillus thuringiensis are under the control of
      the transcriptional regulator PlcR and its regulatory peptide, PapR. In Bacillus
      anthracis, the causative agent of anthrax, PlcR is inactivated by truncation, and
      consequently genes having PlcR binding sites are expressed at very low levels
      when compared with B. cereus. We found that activation of the PlcR regulon in B.
      anthracis by expression of a PlcR-PapR fusion protein does not alter sporulation
      in strains containing the virulence plasmid pXO1 and thereby the global regulator
      AtxA. Using comparative 2D gel electrophoresis, we showed that activation of the
      PlcR regulon in B. anthracis leads to upregulation of many proteins found in the
      secretome of B. cereus, including phospholipases and proteases, such as the
      putative protease BA1995. Transcriptional analysis demonstrated expression of
      BA1995 to be dependent on PlcR-PapR, even though the putative PlcR recognition
      site of the BA1995 gene does not exactly match the PlcR consensus sequence,
      explaining why this protein had escaped recognition as belonging to the PlcR
      regulon. Additionally, while transcription of major PlcR-dependent haemolysins,
      sphingomyelinase and anthrolysin O is enhanced in response to PlcR activation in
      B. anthracis, only anthrolysin O contributes significantly to lysis of human
      erythrocytes. In contrast, the toxicity of bacterial culture supernatants from a
      PlcR-positive strain towards murine macrophages occurred independently of
      anthrolysin O expression in vitro and in vivo.

PMID- 20688833
TI  - Association of CYP19A1 polymorphisms with risks for atypical adenomatous
      hyperplasia and bronchioloalveolar carcinoma in the lungs.
AB  - Estrogen has been indicated to play an etiological role in the development of
      lung adenocarcinoma (ADC), particularly bronchioloalveolar carcinoma (BAC), a
      type of ADC that develops from a benign adenomatous lesion, atypical adenomatous
      hyperplasia (AAH). Polymorphisms in the CYP19A1 gene cause interindividual
      differences in estrogen levels. Here, 13 CYP19A1 single-nucleotide polymorphisms
      (SNPs) were examined for associations with lung AAH risk. AAH is detected as
      ground-glass opacity (GGO) by computed tomography (CT) examination, and this
      study consisted of 100 individuals diagnosed with GGO in their lungs among 3088
      CT-based cancer screening examinees and 424 without. Minor allele carriers for
      the rs3764221 SNP showed an elevated risk for GGO [odds ratio (OR) = 1.72, P =
      0.017]. Associations of this SNP with risks for lung AAH and BAC in the lungs
      were next examined using 359 ADC cases whose resected lung lobes were subjected
      to a histological examination for AAH accompaniment and the presence of BAC
      components and 330 controls without cancer. The ORs were also increased for lung
      ADC accompanied by AAH (OR = 1.74, P = 0.029) as well as lung ADC with BAC
      components (OR = 1.41, P = 0.091). The minor allele was associated with an
      increased circulating estradiol level (P = 0.079) in a population of 363
      postmenopausal women without cancer. These results indicate that CYP19A1
      polymorphisms are involved in the risk for lung AAH and BAC in the lungs by
      causing differences in estrogen levels.

PMID- 20688834
TI  - Suppression of colitis-driven colon cancer in mice by a novel small molecule
      inhibitor of sphingosine kinase.
AB  - Sphingolipid metabolism is driven by inflammatory cytokines. These cascade of
      events include the activation of sphingosine kinase (SK), and subsequent
      production of the mitogenic and proinflammatory lipid sphingosine 1-phosphate
      (S1P). Overall, S1P is one of the crucial components in inflammation, making SK
      an excellent target for the development of new anti-inflammatory drugs. We have
      recently shown that SK inhibitors suppress colitis and hypothesize here that the
      novel SK inhibitor, ABC294640, prevents the development of colon cancer. In an
      azoxymethane (AOM)/dextran sulfate sodium (DSS) mouse model, there was a dose
      dependent decrease in tumor incidence with SK inhibitor treatment. The tumor
      incidence (number of animals with tumors per group) in the vehicle, ABC294640 (20
      mg/kg) and ABC294640 (50 mg/kg) groups were 80, 40 and 30%, respectively. Tumor
      multiplicity (number of tumors per animal) also decreased from 2.1 +/- 0.23
      tumors per animal in the AOM + DSS + vehicle group to 1.2 +/- 0 tumors per animal
      in the AOM + DSS + ABC294640 (20 mg/kg) and to 0.8 +/- 0.4 tumors per animal in
      the AOM + DSS + ABC294640 (50 mg/kg) group. Importantly, with ABC294640, there
      were no observed toxic side effects. To explore mechanisms, we isolated cells
      from the colon (CD45-, representing primarily colon epithelial cells) and (CD45+,
      representing primarily colon inflammatory cells) then measured known targets of
      SK that control cell survival. Results are consistent with the hypothesis that
      the inhibition of SK activity by our novel SK inhibitor modulates key pathways
      involved in cell survival and may be a viable treatment strategy for the
      chemoprevention colitis-driven colon cancer.

PMID- 20688835
TI  - Enhancement of ultraviolet B-induced skin tumor development in phospholipase
      Cepsilon-knockout mice is associated with decreased cell death.
AB  - Phospholipase C (PLC) epsilon is a phosphoinositide-specific PLC regulated by
      small guanosine triphosphatases including Ras and Rap. Our previous studies
      revealed that PLCepsilon gene-knockout (PLCepsilon(-/-)) mice exhibit marked
      resistance to tumor formation in two-stage skin chemical carcinogenesis using
      7,12-dimethylbenz(a)anthracene as an initiator and 12-O-tetradecanoylphorbol-13
      acetate as a promoter. In this model, PLCepsilon functions in tumor promotion
      through augmentation of 12-O-tetradecanoylphorbol-13-acetate-induced
      inflammation. In this study, we have further assessed the role of PLCepsilon in
      tumorigenesis using a mouse model of ultraviolet (UV) B-induced skin tumor
      development. We irradiated PLCepsilon(+/+), PLCepsilon(+/-) or PLCepsilon(-/-)
      mice with doses of UVB increasing from 1 to 10 kJ/m(2) three times a week for a
      total of 25 weeks and observed tumor formation for up to 50 weeks. In sharp
      contrast to the results from the two-stage chemical carcinogenesis study,
      PLCepsilon(-/-) mice developed a large number of neoplasms including malignant
      tumors, whereas PLCepsilon(+/+) and PLCepsilon(+/-) mice developed a relatively
      small number of benign tumors. However, UVB-induced skin inflammation was greatly
      suppressed in PLCepsilon(-/-) mice, as observed with 12-O-tetradecanoylphorbol-13
      acetate-induced inflammation, implying that PLCepsilon's role in the suppression
      of UVB-induced tumorigenesis is not mediated by inflammation. Studies of the
      tumor initiation stage revealed that UVB-induced cell death in the skin was
      markedly suppressed in PLCepsilon(-/-)mice. Our findings identify a novel
      function for PLCepsilon as a critical molecule regulating UVB-induced cell death
      and suggest that resistance to UVB-induced cell death conferred by the absence of
      PLCepsilon is closely related to the higher incidence of skin tumor formation.

PMID- 20688836
TI  - Can dementia be prevented?

PMID- 20688839
TI  - Survival after diagnosis of dementia in primary care.

PMID- 20688840
TI  - Survival of people with clinical diagnosis of dementia in primary care: cohort
      study.
AB  - OBJECTIVES: To estimate survival after a diagnosis of dementia in primary care,
      compared with people without dementia, and to determine incidence of dementia.
      DESIGN: Cohort study using data from The Health Improvement Network (THIN), a
      primary care database. SETTING: 353 general practices in the United Kingdom
      providing data to THIN. PARTICIPANTS: All adults aged 60 years or over with a
      first ever code for dementia from 1990 to 2007 (n=22 529); random sample of five
      participants without dementia for every participant with dementia matched on
      practice and time period (n=112 645). MAIN OUTCOME MEASURES: Median survival by
      age and sex; mortality rates; incidence of dementia by age, sex, and deprivation.
      RESULTS: The median survival of people with dementia diagnosed at age 60-69 was
      6.7 (interquartile range 3.1-10.8) years, falling to 1.9 (0.7-3.6) years for
      those diagnosed at age 90 or over. Adjusted mortality rates were highest in the
      first year after diagnosis (relative risk 3.68, 95% confidence interval 3.44 to
      3.94). This dropped to 2.49 (2.29 to 2.71) in the second year. The incidence of
      recorded dementia remained stable over time (3-4/1000 person years at risk). The
      incidence was higher in women and in younger age groups (60-79 years) living in
      deprived areas. CONCLUSIONS: Median survival was much lower than in screened
      populations. These clinically relevant estimates can assist patients and carers,
      clinicians, and policy makers when planning support for this population. The high
      risk of death in the first year after diagnosis may reflect diagnoses made at
      times of crisis or late in the disease trajectory. Late recording of diagnoses of
      dementia in primary care may result in missed opportunities for potential early
      interventions.

PMID- 20688841
TI  - Designing prevention programmes to reduce incidence of dementia: prospective
      cohort study of modifiable risk factors.
AB  - OBJECTIVE: To estimate the percentage reduction in incidence of dementia that
      would be obtained if specific risk factors were eliminated. DESIGN: Prospective
      seven year cohort study. SETTING: General population, Montpellier, France.
      PARTICIPANTS: 1433 people aged over 65 with a mean baseline age of 72.5 (SD 5.1)
      years. MAIN OUTCOME MEASURES: Diagnosis of mild cognitive impairment or dementia
      established by a standardised neurological examination. RESULTS: Cox models were
      constructed to derive hazard ratios and determine confounding and interaction
      effects for potentially modifiable risk factors for dementia. Mean percentage
      population attributable fractions were calculated with 95% confidence intervals
      derived from bootstrapping for seven year incidence of mild cognitive impairment
      or dementia. The final model retained crystallised intelligence (population
      attributable fraction 18.11%, 95% confidence interval 10.91% to 25.42%),
      depression (10.31%, 3.66% to 17.17%), fruit and vegetable consumption (6.46%,
      0.15% to 13.06%), diabetes (4.88%, 1.87% to 7.98%), and apolipoprotein E epsilon4
      allele (7.11%, 2.44% to 11.98%). CONCLUSIONS: Increasing crystallised
      intelligence and fruit and vegetable consumption and eliminating depression and
      diabetes are likely to have the biggest impact on reducing the incidence of
      dementia, outweighing even the effect of removing the principal known genetic
      risk factor. Although causal relations cannot be concluded with certainty, the
      study suggests priorities that may inform public health programmes.

PMID- 20688842
TI  - Effect of interpregnancy interval on outcomes of pregnancy after miscarriage:
      retrospective analysis of hospital episode statistics in Scotland.
AB  - OBJECTIVE: To determine the optimum interpregnancy interval after miscarriage in
      a first recorded pregnancy. DESIGN: Population based retrospective cohort study.
      SETTING: Scottish hospitals between 1981 and 2000. PARTICIPANTS: 30,937 women who
      had a miscarriage in their first recorded pregnancy and subsequently became
      pregnant. MAIN OUTCOME MEASURES: The primary end point was miscarriage, live
      birth, termination, stillbirth, or ectopic pregnancy in the second pregnancy.
      Secondary outcomes were rates of caesarean section and preterm delivery, low
      birthweight infants, pre-eclampsia, placenta praevia, placental abruption, and
      induced labour in the second pregnancy. RESULTS: Compared with women with an
      interpregnancy interval of 6-12 months, those who conceived again within six
      months were less likely to have another miscarriage (adjusted odds ratio 0.66,
      95% confidence interval 0.57 to 0.77), termination (0.43, 0.33 to 0.57), or
      ectopic pregnancy (0.48, 0.34 to 0.69). Women with an interpregnancy interval of
      more than 24 months were more likely to have an ectopic second pregnancy (1.97,
      1.42 to 2.72) or termination (2.40, 1.91 to 3.01). Compared with women with an
      interpregnancy interval of 6-12 months, women who conceived again within six
      months and went on to have a live birth in the second pregnancy were less likely
      to have a caesarean section (0.90, 0.83 to 0.98), preterm delivery (0.89, 0.81 to
      0.98), or infant of low birth weight (0.84, 0.71 to 0.89) but were more likely to
      have an induced labour (1.08, 1.02 to 1.23). CONCLUSIONS: Women who conceive
      within six months of an initial miscarriage have the best reproductive outcomes
      and lowest complication rates in a subsequent pregnancy.

PMID- 20688843
TI  - Miscarriage and time to next pregnancy.

PMID- 20688844
TI  - Dietary quercetin intake and risk of gastric cancer: results from a population
      based study in Sweden.
AB  - BACKGROUND: To study the impact of the dietary antioxidant quercetin on risk of
      gastric adenocarcinoma. PATIENTS AND METHODS: Using data from a large Swedish
      population-based case-control study of gastric cancer (505 cases and 1116
      controls), we studied the association between quercetin and risk of anatomic
      (cardia/noncardia) and histological (intestinal and diffuse) subtypes of gastric
      cancer. RESULTS: We found strong inverse associations between quercetin and the
      risk of noncardia gastric adenocarcinoma, with an adjusted odds ratio (OR) of
      0.57 (95% confidence interval 0.40-0.83) for the highest quintile (>=11.9 mg) of
      daily quercetin intake relative to the lowest quintile of intake (<4 mg
      quercetin/day), supported by a significant decreasing linear trend (P value <
      0.001). Similar findings were observed for the intestinal and diffuse subtype.
      For cardia cancer, we found a less evident and nonsignificant inverse
      relationship. The protection of quercetin appeared to be stronger among female
      smokers, with the OR leveled of at values <0.2 in quintiles 3-5 (>6 mg
      quercetin/day). CONCLUSIONS: High dietary quercetin intake is inversely related
      to the risk of noncardia gastric adenocarcinoma, and the protection appears to be
      particularly strong for women exposed to oxidative stress, such as tobacco
      smoking.

PMID- 20688845
TI  - Primary percutaneous coronary intervention in ST-segment elevation myocardial
      infarction is more effective than fibrinolysis at reducing the composite outcome
      of death or reinfarction after 8 years.

PMID- 20688846
TI  - Once-only flexible sigmoidoscopy screening for adults aged 55-64 years old
      reduces the incidence of colorectal cancer and colorectal cancer deaths.

PMID- 20688847
TI  - B-type natriuretic peptide-guided therapy for chronic heart failure reduces all
      cause mortality compared with usual care but does not affect all-cause
      hospitalisation or survival free of hospitalisation.

PMID- 20688848
TI  - Identifying and managing cow's milk protein allergy.
AB  - Cow's milk protein (CMP) is usually one of the first complementary foods to be
      introduced into the infant's diet and is commonly consumed throughout childhood
      as part of a balanced diet. CMP is capable of inducing a multitude of adverse
      reactions in children, which may involve organs like the skin, gastrointestinal
      (GI) tract or respiratory system. The diagnosis of CMP-induced adverse reactions
      requires an understanding of their classification and immunological basis as well
      as the strengths and limitations of diagnostic modalities. In addition to the
      well-recognised, immediate-onset IgE-mediated allergies, there is increasing
      evidence to support the role of CMP-induced allergy in a spectrum of delayed
      onset disorders ranging from GI symptoms to chronic eczema. The mainstay of
      treatment is avoidance of CMP; this requires dietetic input to ensure that this
      does not lead to any nutritional compromise. This review is intended to highlight
      the broad spectrum of manifestations of CMP allergy and to offer an approach to
      the diagnosis and treatment thereof.

PMID- 20688849
TI  - What's bugging you? An update on the treatment of head lice infestation.
AB  - Head lice infestation (pediculosis capitis) is a common problem in paediatric
      practice. It can cause considerable distress to children and their families and
      may lead to bullying and social stigmatisation. Therapy with "conventional"
      topical pediculicides with neurotoxic mode of action-such as malathion,
      permethrin, phenothrin and carbaryl-is increasingly associated with treatment
      failure as a result of the emergence of resistance within the parasite
      population. This review provides an overview of the natural history, clinical
      symptoms and diagnosis of head lice infestation. It also discusses general
      management principles and summarises the current data on novel treatment
      strategies, including wet combing, dimeticone, isopropyl myristate, benzyl
      alcohol, plant-based compounds and oral medication.

PMID- 20688854
TI  - Epistle.

PMID- 20688855
TI  - Recognising heart disease in children with Down syndrome.

PMID- 20688856
TI  - Foreign bodies in the chest.

PMID- 20688857
TI  - Interpretations: How to use faecal elastase testing.

PMID- 20688858
TI  - Educational supervision.

PMID- 20688861
TI  - Continuing utilisation of specialised health services in extremely preterm
      infants.
AB  - OBJECTIVE: To compare healthcare use from neonatal discharge to 18 months
      corrected age (CA) of two groups of extremely preterm neonates (23-25 vs 26-28
      weeks). DESIGN: Cohort study. PATIENTS: Infants born at < or =28 weeks and
      admitted in three hospital centres in Quebec, Canada (n=254). MAIN OUTCOME
      MEASURES: Neurodevelopmental outcomes and healthcare use from neonatal discharge
      to 18 months CA. RESULTS: Re-hospitalisation rates occurred in 57% of children
      born at 23-25 weeks and in 49% of those born at 26-28 weeks. In these two age
      groups, by 18 months, 61% vs 59% were followed in physical or occupational
      therapy, 29% vs 17% were enrolled in a long-term rehabilitation program, 38% vs
      28% used prescribed medication, and 59% vs 33% required medical assistive
      devices, respectively. Risk of re-hospitalisation was related to bronchopulmonary
      dysplasia (BPD), severe brain injury, use of home oxygen or an apnoea monitor and
      older age at neonatal discharge. Multiple births, BPD, severe brain injury, older
      age at neonatal discharge and single parenthood were associated with risk of
      using out-patient health services above average (>2 services). CONCLUSION:
      Extremely preterm children are frequently re-hospitalised during infancy and use
      a substantial amount of healthcare resources. These results highlight the
      importance of resource allocation to preterm infants for medical and
      rehabilitation services after discharge from the neonatal intensive care unit.

PMID- 20688862
TI  - Work of breathing and volume targeted ventilation in respiratory distress.
AB  - OBJECTIVE: To determine the level of volume targeting (VT) associated with the
      lowest work of breathing (WOB) for prematurely born infants being ventilated with
      acute respiratory distress. DESIGN: Prospective study. SETTING: Tertiary neonatal
      intensive care unit. PATIENTS: 18 infants, median gestational age 29 (range 25
      34) weeks, being ventilated for acute respiratory distress. INTERVENTIONS:
      Infants were studied first without VT (baseline). Volume targeted levels of 4
      ml/kg, 5 ml/kg and 6 ml/kg were then delivered in random order. After each VT
      level, the infants were returned to baseline. Each step was maintained for 20
      minutes. MAIN OUTCOME MEASURE: The transdiaphragmatic pressure time product
      (PTPdi) as an estimate of the WOB. RESULTS: The mean PTPdi was higher at a VT
      level of 4 ml/kg (median 154 cm H(2)O.s/min) compared to baseline (median 112 cm
      H(2)O.s/min) (p<0.001) and a VT level of 6 ml/kg (median 89 cm H(2)O.s/min)
      (p<0.001). CONCLUSION: A low level of VT increased the WOB in infants with acute
      respiratory distress syndrome. The authors' results suggest that, during acute
      respiratory distress, a VT level of at least 5 ml/kg rather than a lower level
      might avoid an increased WOB. The most appropriate level of VT needs to be
      determined in a randomised controlled trial with long-term outcomes.

PMID- 20688863
TI  - Monitoring of seizures in the newborn.
AB  - Neonatal seizures are a distinct and not uncommon sign of neurological disease in
      the newborn, most often occurring in association with hypoxic-ischaemic
      encephalopathy at term. The diagnosis and monitoring of seizures in the newborn
      is a considerable challenge, with many suspected clinical seizures having no
      electrographic correlates, while many electrographic seizures have no clinical
      correlate. Continuous video-EEG is the gold standard for seizure monitoring, but
      few centres have the resources or expertise required. Amplitude-integrated EEG
      can be a helpful monitoring tool in experienced hands, but has potential for
      error when used by inexperienced staff. Automated seizure detection algorithms
      show much promise and some cotside systems are already available. The efficiency
      and accuracy of these systems is likely to improve.

PMID- 20688864
TI  - Am I getting chest wall movement?

PMID- 20688865
TI  - Early versus late MRI in asphyxiated newborns treated with hypothermia.
AB  - OBJECTIVE: The purposes of this feasibility study were to assess: (1) the
      potential utility of early brain MRI in asphyxiated newborns treated with
      hypothermia; (2) whether early MRI predicts later brain injury observed in these
      newborns after hypothermia has been completed; and (3) whether early MRI
      indicators of brain injury in these newborns represent reversible changes.
      PATIENTS AND METHODS: All consecutive asphyxiated term newborns meeting the
      criteria for therapeutic hypothermia were enrolled prospectively. Each newborn
      underwent one or two early MRI scans while receiving hypothermia, on day of life
      (DOL) 1 and DOL 2-3 and also one or two late MRI scans on DOL 8-13 and at 1 month
      of age. RESULTS: 37 MRI scans were obtained in 12 asphyxiated neonates treated
      with induced hypothermia. Four newborns developed MRI evidence of brain injury,
      already visible on early MRI scans. The remaining eight newborns did not develop
      significant MRI evidence of brain injury on any of the MRI scans. In addition,
      two patients displayed unexpected findings on early MRIs, leading to early
      termination of hypothermia treatment. CONCLUSIONS: MRI scans obtained on DOL 2-3
      during hypothermia seem to predict later brain injuries in asphyxiated newborns.
      Brain injuries identified during this early time appear to represent irreversible
      changes. Early MRI scans might also be useful to demonstrate unexpected findings
      not related to hypoxic-ischaemic encephalopathy, which could potentially be
      exacerbated by induced hypothermia. Additional studies with larger numbers of
      patients will be useful to confirm these results.

PMID- 20688866
TI  - Understanding and managing breast milk jaundice.
AB  - The breastfed infant with prolonged unconjugated hyperbilirubinaemia can present
      a vexing clinical dilemma. Although it is a frequently observed and usually
      benign finding, prolonged jaundice in the breastfed newborn requires a thoughtful
      evaluation that excludes possible pathological aetiologies. While recommendations
      for the treatment of unconjugated hyperbilirubinaemia in the first 7 days of life
      are straightforward, the approach to the breastfeeding infant with jaundice that
      persists beyond the immediate neonatal period is less clearly delineated. A sound
      understanding of bilirubin physiology and familiarity with current literature
      must guide the management of the otherwise well breastfeeding infant with
      prolonged unconjugated hyperbilirubinaemia.

PMID- 20688867
TI  - Antecedents of chronic lung disease following three patterns of early respiratory
      disease in preterm infants.
AB  - INTRODUCTION: The incidence of chronic lung disease (CLD) varies among groups
      defined by their early pattern of respiratory disease. METHODS: The study
      examined data collected prospectively on 1204 of the 1506 infants born in 2002
      2004 at 23-27 weeks gestation who survived to 36 weeks post-menstrual age. Based
      on their initial respiratory presentation and need for supplemental oxygen during
      the first 2 weeks, infants were classified as having early and persistent
      pulmonary dysfunction (EPPD), early recovery of pulmonary function followed by
      deterioration (PD) or consistently good pulmonary function characterised by low
      FiO(2) (Low FiO(2)). RESULTS: CLD was diagnosed in 69% of infants with EPPD, 52%
      with PD, and 17% in the Low FiO(2) group. Birth weight z score <-1 conveyed
      information about CLD risk in all three groups and was the major risk factor for
      infants in the Low FiO(2) group (OR 27; 95% CI 7 to 95). Mechanical ventilation
      at 7 days was associated with increased risk in the PD (OR 4.2, 95% CI 2.5 to
      6.9) and EPPD groups (OR 2.7, 95% CI 1.5 to 4.7), but not the Low FiO(2) group
      (OR 1.5, 95% CI 0.5 to 3.9). CONCLUSION: The likelihood of a very preterm infant
      developing CLD and the profile of risk factors linked with CLD are related to the
      infant's pattern of respiratory disease during the first 2 postnatal weeks. Among
      infants with little exposure to oxygen during this period, fetal growth
      restriction, not mechanical ventilation, is the factor with the strongest
      association with CLD.

PMID- 20688868
TI  - Three distinct peptides from the N domain of translation termination factor eRF1
      surround stop codon in the ribosome.
AB  - To study positioning of the polypeptide release factor eRF1 toward a stop signal
      in the ribosomal decoding site, we applied photoactivatable mRNA analogs,
      derivatives of oligoribonucleotides. The human eRF1 peptides cross-linked to
      these short mRNAs were identified. Cross-linkers on the guanines at the second,
      third, and fourth stop signal positions modified fragment 31-33, and to lesser
      extent amino acids within region 121-131 (the "YxCxxxF loop") in the N domain.
      Hence, both regions are involved in the recognition of the purines. A cross
      linker at the first uridine of the stop codon modifies Val66 near the NIKS loop
      (positions 61-64), and this region is important for recognition of the first
      uridine of stop codons. Since the N domain distinct regions of eRF1 are involved
      in a stop-codon decoding, the eRF1 decoding site is discontinuous and is not of
      "protein anticodon" type. By molecular modeling, the eRF1 molecule can be fitted
      to the A site proximal to the P-site-bound tRNA and to a stop codon in mRNA via a
      large conformational change to one of its three domains. In the simulated eRF1
      conformation, the YxCxxxF motif and positions 31-33 are very close to a stop
      codon, which becomes also proximal to several parts of the C domain. Thus, in the
      A-site-bound state, the eRF1 conformation significantly differs from those in
      crystals and solution. The model suggested for eRF1 conformation in the ribosomal
      A site and cross-linking data are compatible.

PMID- 20688869
TI  - Mapping U.S. government tobacco control leadership: networked for success?
AB  - INTRODUCTION: In order to better understand how tobacco control efforts are
      coordinated across agencies of the Department of Health and Human Services
      (DHHS), we assessed tobacco control-related communication between tobacco control
      leaders across DHHS. METHODS: Cross-sectional surveys were collected from
      individuals representing 11 DHHS agencies, and social network analyses were used
      to assess linkages and map agencies' tobacco control communication. RESULTS:
      Individuals within the Office of the Secretary and Centers for Disease Control
      and Prevention (CDC) were most central to the network, and those of highest rank
      were most likely to be central to the network (F = 4.03, p = .024). The Centers
      for Medicare and Medicaid Services, Food and Drug Administration, Health
      Resources and Services Administration, and Substance Abuse and Mental Health
      Services Administration had no or almost no contact with other agencies. There
      was considerable between-agency contact variability, and the CDC was the most
      central agency. DISCUSSION: Tobacco control communication across DHHS agencies
      was present but extremely variable. This inconsistency may compromise the ability
      of the DHHS to address tobacco use, a critical public health problem, in a
      coordinated and efficient fashion. In light of the new leadership at DHHS, this
      analysis describes a systems approach that can be reimplemented as a means of
      understanding and improving communication and collaboration to improve public
      health.

PMID- 20688870
TI  - A social contextual analysis of youth cigarette smoking development.
AB  - INTRODUCTION: We apply a social contextual perspective based on Bronfenbrenner's
      ecology of human development theory to understanding development of youth
      cigarette smoking. We examine the contributions of family, peer, school, and
      neighborhood contexts. Context attributes examined were derived from social
      learning and social control theories. METHODS: Data are from 6,544 youth who
      participated in at least one of five waves of data collection between Spring 2002
      and Spring 2004, 1,663 randomly selected parents who participated in one or more
      of three waves of data collection in the same time period; and the U.S. Census.
      Three-level hierarchical growth models were used to examine the contributions of
      time-varying measures of the four social contexts to development of smoking from
      age 11-17 years. Interactions between variables were examined within and between
      social contexts. RESULTS: Attributes of each social context made independent
      contributions to adolescent smoking development; there also were significant
      interactions between variables from different contexts indicating joint
      contextual effects. Attributes of the social bond moderated exposure to models of
      smoking within and between the family and peer contexts. DISCUSSION: Results
      suggest the value of a social contextual perspective in research on the etiology
      of youth smoking development as well as the utility of guidance by social
      learning and social control theories. While all contexts were implicated in
      adolescent smoking, the family and peer contexts were primarily implicated, with
      findings suggesting the need for consideration of interactive effects between
      social learning and social control variables within and between these contexts.

PMID- 20688871
TI  - The psychosis susceptibility gene ZNF804A: associations, functions, and
      phenotypes.
AB  - As the first gene to have achieved genome-wide significance for psychosis,
      ZNF804A has predictably been a subject of intense research activity. We review
      the evidence to date for the association between schizophrenia and the original
      risk variant rs1344706 identified as well as additional common and rare variants
      at this locus. We describe the still scant literature on the biological function
      of ZNF804A and discuss the efforts being made to characterize and refine the
      associated phenotype using imaging and neuropsychological approaches. We conclude
      that ZNF804A is robustly, if modestly, associated with schizophrenia risk, with
      much work still remaining to elucidate its role in schizophrenia biology.

PMID- 20688872
TI  - How can movement quality be promoted in clinical practice? A phenomenological
      study of physical therapist experts.
AB  - BACKGROUND: In recent years, physical therapists have paid greater attention to
      body awareness. Clinicians have witnessed the benefits of supporting their
      patients' learning of movement awareness through the promotion of their movement
      quality. OBJECTIVE: The aim of this study was to investigate how physical
      therapist experts promote movement quality in their usual clinical settings.
      DESIGN: A phenomenological research design that included a sampling strategy was
      devised. Using specific criteria, 6 lead physical therapists nominated a group of
      physical therapist experts from the fields of neurology, primary health care, and
      mental health. Fifteen informants, 5 from each field, agreed to participate.
      METHODS: In-depth interviews were conducted with a semistructured interview
      guide. The informants were invited to simply describe what they had experienced
      to be successful therapeutic processes for promoting movement quality. Each
      interview was audiotaped and transcribed. The data analysis was based on a
      multistep model. RESULTS: Three main themes emerged from the data. First, the
      physical therapists' embodied presence and movement awareness served as a
      precondition and an orientation for practice. Embodied presence is a bodily felt
      sense, a form of personal knowing that evokes understanding and fosters meaning.
      Second, creating a platform for promoting movement quality revealed
      implementation of psychological attitudes. Third, action strategies for promoting
      movement quality suggested a movement awareness learning cycle and components for
      clinical use. CONCLUSIONS: This study demonstrated specific attitudes and skills
      used by physical therapist experts to promote movement quality in their clinical
      practice. These results may serve as a therapeutic framework for promoting
      movement quality in clinical physical therapy, although further research is
      needed.

PMID- 20688873
TI  - Intervention goals determine physical therapists' workload in the acute care
      setting.
AB  - BACKGROUND: Investigating determinants of physical therapy workload in the acute
      care setting is essential for planning interventions, for justifying resource
      allocation, and for reimbursement. OBJECTIVE: The objective of this study was to
      examine whether International Classification of Functioning, Disability and
      Health (ICF) intervention goals (ICF categories representing goals of physical
      therapy interventions typical for an acute care hospital) could predict physical
      therapy workload in the acute care hospital setting. DESIGN: This investigation
      was a multicenter, observational cohort study. METHODS: Patients were recruited
      from a representative sample of 32 acute care hospitals across Switzerland if
      they received physical therapy during their inpatient stay for the treatment of
      any injury or disease in 1 of 3 main diagnostic categories: musculoskeletal,
      neurological, and cardiopulmonary conditions. Physical therapists completed
      questionnaires at the time of the patients' discharge to report on ICF
      intervention goals. Information on workload was collected retrospectively from
      hospital documentation systems. Multivariable regression models were used to
      identify the intervention goals independently associated with workload. RESULTS:
      The mean workload for 642 patients (mean age=61 years [SD=18 years], 45% women)
      was 370 minutes. The daily workload for interventions ranged from 33 minutes
      (cardiopulmonary conditions) to 49 minutes (neurological conditions). There were
      significant variations in workload across hospital sites and medical disciplines.
      The goal "maintaining a body position" emerged as a significant indicator of a
      higher workload for all condition groups; the goals "attention functions" and
      "transferring oneself" were indicators for neurological and musculoskeletal
      conditions, respectively. LIMITATIONS: Not all potential predictors of workload
      could be examined. Other, person- or setting-specific variables might have been
      relevant to workload. Case mix and clinical practice were representative only for
      Swiss hospitals. CONCLUSIONS: A small set of intervention goals were the major
      factors influencing physical therapy workload, independent of diagnosis or
      clinical specialty. Describing variability in physical therapists' practices in
      the acute care setting and relating these data to relevant patient-centered
      outcomes are the initial steps for improving resource allocation and
      reimbursement for interventions that maintain or improve functioning.

PMID- 20688874
TI  - Development of a unique triage system for acute care physical therapy and
      occupational therapy services: an administrative case report.
AB  - BACKGROUND AND PURPOSE: This administrative case report documents the development
      of a mechanism by which systematic triage was used to assign patients to
      therapists in acute care settings. The primary objective was to develop a triage
      tool to improve patient access to medically necessary therapy services. CASE
      DESCRIPTION: A unique triage tool and a decision tree were developed to determine
      which patients referred to therapists for acute care therapy required skilled
      services. The triage tool was used to examine therapy referrals for patients from
      2 large academic hospitals; 6 criteria were used to determine which evaluations
      should be cancelled. During the trial period, the predictive ability of
      individual triage criterion items was analyzed, the tool was modified and
      validated, and a decision tree was established. Descriptive and chi-square
      analyses were performed on all variables of interest. OUTCOMES: The systematic
      triage system reduced the number of therapy evaluations that were not appropriate
      by 29%, resulting in an improvement in the availability of therapy services for
      patients who required skilled care. The average number of patients per therapist
      per workday decreased from 18.9 to 12.1 and from 15.1 to 12.8 in the 2 hospitals.
      An improvement in a newly developed "workload index" related to missed patient
      visits also indicated the success of this project. DISCUSSION: A novel systematic
      triage system reduced the number of therapy evaluations that were not
      appropriate, resulting in an improvement in the availability of therapy services
      for patients who require skilled intervention.

PMID- 20688875
TI  - Effects of statins on skeletal muscle: a perspective for physical therapists.
AB  - Hyperlipidemia, also known as high blood cholesterol, is a cardiovascular health
      risk that affects more than one third of adults in the United States. Statins are
      commonly prescribed and successful lipid-lowering medications that reduce the
      risks associated with cardiovascular disease. The side effects most commonly
      associated with statin use involve muscle cramping, soreness, fatigue, weakness,
      and, in rare cases, rapid muscle breakdown that can lead to death. Often, these
      side effects can become apparent during or after strenuous bouts of exercise.
      Although the mechanisms by which statins affect muscle performance are not
      entirely understood, recent research has identified some common causative
      factors. As musculoskeletal and exercise specialists, physical therapists have a
      unique opportunity to identify adverse effects related to statin use. The
      purposes of this perspective article are: (1) to review the metabolism and
      mechanisms of actions of statins, (2) to discuss the effects of statins on
      skeletal muscle function, (3) to detail the clinical presentation of statin
      induced myopathies, (4) to outline the testing used to diagnose statin-induced
      myopathies, and (5) to introduce a role for the physical therapist for the
      screening and detection of suspected statin-induced skeletal muscle myopathy.

PMID- 20688876
TI  - Nationwide acute care physical therapist practice analysis identifies knowledge,
      skills, and behaviors that reflect acute care practice.
AB  - BACKGROUND: Acute care physical therapy is a rapidly evolving practice area, but
      little is known about the skills, knowledge, and behaviors necessary for a
      clinician to be most effective in this area. OBJECTIVE: The objective of this
      study was to perform the first nationwide survey of acute care physical
      therapists to validate the knowledge, skill, and behavior sets that reflect
      practice parameters specific for acute care physical therapy. DESIGN: A survey
      format was used. METHODS: The Acute Care Physical Therapy Practice Analysis
      Survey was created on the basis of current literature and consensus of a 9-member
      Subject Matter Expert (SME) Group. The survey sections addressed knowledge areas,
      professional behaviors, and patient/client management approaches reflecting
      practice parameters specific for acute care physical therapy. Additionally,
      respondent demographic information was collected. Pilot testing necessitated
      minor changes in the survey. After revision, the survey questionnaire was sent to
      a sample of experienced acute care physical therapists throughout the United
      States. RESULTS: A convenience sample of 522 physical therapists who identified
      themselves as having extensive experience in acute care practice was used. Of
      these, 254 completed the survey, for a response rate of 48.7%. Through the use of
      predetermined decision rules, 34 items were eliminated on the basis of a
      descriptive analysis of survey results as well as a failure of the items to meet
      the threshold of specificity for acute care practice, as determined through SME
      Group consensus. LIMITATIONS: The potential for self-selection bias, a sample
      weighted heavily with American Physical Therapy Association members and Acute
      Care Section members, and a small proportion of clinicians (<3%) with less than 1
      year of acute care experience may limit generalizability of these results.
      CONCLUSIONS: The results of this practice analysis describe distinct knowledge,
      skills, and behaviors specific for acute care physical therapy. The outcomes of
      the survey might assist in the development of professional (entry-level) acute
      care competencies, a petition for the recognition of specialization in acute care
      physical therapy, or both. In addition, the findings of this practice analysis
      could serve as the foundation for the development of residencies or fellowships
      in acute care practice.

PMID- 20688878
TI  - Transforming growth factor-beta1-mediated activation of NF-kappaB contributes to
      enhanced ADAM-12 expression in mammary carcinoma cells.
AB  - A disintegrin and metalloproteinase-12 (ADAM-12), a member of multifunctional
      family of proteins, is upregulated in many cancers, including breast, lung,
      liver, prostate, gastric, and bladder. The multidomain structure, composed of a
      prodomain, a metalloproteinase, disintegrin-like, epidermal growth factor-like,
      cysteine-rich and transmembrane domains, and a cytoplasmic tail, allows ADAM-12
      to promote matrix degradation, cell-cell adhesion, and intracellular signaling
      capacities and thereby to play a critical role in cancer growth and metastasis.
      Despite ample evidence linking increased ADAM-12 expression with cancer, the
      mechanisms controlling its upregulation are still unknown. In the present study,
      transforming growth factor-beta1 (TGF-beta1) is shown to increase ADAM-12 mRNA
      expression in MDA-MB-231 breast carcinoma cells. We have identified a promoter
      element responsible for TGF-beta1-mediated ADAM-12 induction. We show interaction
      of NF-kappaB with ADAM-12 promoter and that high level of NF-kappaB activity in
      breast carcinoma cells results in the upregulation of ADAM-12 expression. Site
      directed mutagenesis of the NF-kappaB element in ADAM-12 promoter and inhibition
      of NF-kappaB activity by Bay-11-7085 and MG-132 significantly reduced TGF-beta1
      mediated increase of ADAM-12 promoter-driven gene expression. Transfection of
      cells with a dominant-negative mutant form of IkappaBalpha (IkappaBalphaDeltaN),
      which inhibits activation of NF-kappaB, significantly reduced transcription from
      ADAM-12 promoter-reporter in TGF-beta1-stimulated MDA-MB-231 cancer cells. In
      correlation, overexpression of NF-kappaB induced ADAM-12 expression in a dose
      dependent manner. DNA-binding and ChIP assays indicated that p65 subunit of NF
      kappaB binds to ADAM-12 promoter. Together, our study identified a cellular
      mechanism for induction of ADAM-12, which involves NF-kappaB and its activation
      by TGF-beta1.

PMID- 20688877
TI  - Striatal and medial temporal lobe functional interactions during visuomotor
      associative learning.
AB  - A network of regions including the medial temporal lobe (MTL) and the striatum
      are integral to visuomotor associative learning. Here, we evaluated the
      contributions of the structures of the striatum and the MTL, as well as their
      interactions during an arbitrary associative learning task. We hypothesized that
      activity in the striatum would correlate with the rate of learning, while
      activity in the MTL would track how well associations were learned. Further, we
      expected functional correlations to show both facilitative as well as competitive
      relationships depending on the regions involved. Results showed that activity
      throughout the striatum was modulated by the rate of learning, while the
      sensorimotor and ventral striatum were also modulated by probability correct.
      Across the MTL, activity correlated with the probability of being correct, while
      the perirhinal cortex and right parahippocampal cortex were modulated by the rate
      of learning. The activity in the ventral striatum robustly coupled with activity
      in the MTL during learning, while interactions between the associative striatum
      and the MTL showed the opposite pattern. These findings suggest dissociable
      computational roles for different subregions of the striatum and MTL. These
      subregions interact in distinct ways, perhaps forming functionally integrated
      networks during the learning of arbitrary associations.

PMID- 20688879
TI  - Expanding leaves of mature deciduous forest trees rapidly become autotrophic.
AB  - Emerging leaves in evergreen tree species are supplied with carbon (C) from the
      previous year's foliage. In deciduous trees, no older leaves are present, and the
      early phase of leaf development must rely on C reserves from other tissues. How
      soon developing leaves become autotrophic and switch from being C sinks to
      sources has rarely been studied in mature forest trees, and simultaneous
      comparisons of species are scarce. Using a canopy crane and a simple (13)CO(2)
      pulse-labelling technique, we demonstrate that young leaves of mature trees in
      three European deciduous species (Fagus sylvatica L., Quercus petraea (Matt.)
      Liebl., Tilia platyphyllos Scop.) start assimilating CO(2) at a very early stage
      of development (10-50% expanded). One month after labelling, all leaves were
      still strongly (13)C enriched, suggesting that recent photosynthates had been
      incorporated into slow turnover pools such as cellulose or lignin and thus had
      contributed to leaf growth. In line with previous studies performed at the same
      site, we found stronger incorporation of recent photosynthates into growing
      tissues of T. platyphyllos compared with F. sylvatica and Q. petraea. Non
      structural carbohydrate (NSC) concentrations analysed for one of the three study
      species (F. sylvatica) showed that sugar and starch pools rapidly increased
      during leaf development, suggesting that newly developed leaves soon produce more
      NSC than can be used for growth. In conclusion, our findings indicate that
      expanding leaves of mature deciduous trees become C autonomous at an early stage
      of development despite the presence of vast amounts of mobile carbohydrate
      reserves.

PMID- 20688880
TI  - Nickel-tolerant ectomycorrhizal Pisolithus albus ultramafic ecotype isolated from
      nickel mines in New Caledonia strongly enhance growth of the host plant
      Eucalyptus globulus at toxic nickel concentrations.
AB  - Ectomycorrhizal (ECM) Pisolithus albus (Cooke & Massee), belonging to the
      ultramafic ecotype isolated in nickel-rich serpentine soils from New Caledonia (a
      tropical hotspot of biodiversity) and showing in vitro adaptive nickel tolerance,
      were inoculated to Eucalyptus globulus Labill used as a Myrtaceae plant-host
      model to study ectomycorrhizal symbiosis. Plants were then exposed to a nickel
      (Ni) dose-response experiment with increased Ni treatments up to 60 mg kg( - )(1)
      soil as extractable Ni content in serpentine soils. Results showed that plants
      inoculated with ultramafic ECM P. albus were able to tolerate high and toxic
      concentrations of Ni (up to 60 MUg g( - )(1)) while uninoculated controls were
      not. At the highest Ni concentration tested, root growth was more than 20-fold
      higher and shoot growth more than 30-fold higher in ECM plants compared with
      control plants. The improved growth in ECM plants was associated with a 2.4-fold
      reduction in root Ni concentration but a massive 60-fold reduction in transfer of
      Ni from root to shoots. In vitro, P. albus strains could withstand high Ni
      concentrations but accumulated very little Ni in its tissue. The lower Ni uptake
      by mycorrhizal plants could not be explained by increased release of metal
      complexing chelates since these were 5- to 12-fold lower in mycorrhizal plants at
      high Ni concentrations. It is proposed that the fungal sheath covering the plant
      roots acts as an effective barrier to limit transfer of Ni from soil into the
      root tissue. The degree of tolerance conferred by the ultramafic P. albus
      isolates to growth of the host tree species is considerably greater than
      previously reported for other ECM. The primary mechanisms underlying this
      improved growth were identified as reduced Ni uptake into the roots and markedly
      reduced transfer from root to shoot in mycorrhizal plants. The fact that these
      positive responses were observed at Ni concentrations commonly observed in
      serpentinic soils suggests that ultramafic ecotypes of P. albus could play an
      important role in the adaptation of tree species to soils containing high
      concentrations of heavy metals and aid in strategies for ecological restoration.

PMID- 20688881
TI  - Nuclear androgen receptor staining in bone metastases is related to a poor
      outcome in prostate cancer patients.
AB  - Androgen receptors (ARs) are probably of importance during all phases of prostate
      cancer (PC) growth, but their role in bone metastases is largely unexplored. Bone
      metastases were therefore collected from hormone-naive (n=11), short-term
      castrated (n=7) and castration-resistant PC (CRPC, n=44) patients by biopsy (n=4)
      or at surgery to alleviate symptoms from metastases complications (metastasis
      surgery, n=58), and immunostained for nuclear ARs, Ki67, active caspase-3,
      prostate-specific antigen (PSA) and chromogranin A, and results were related to
      serum PSA, treatments and outcome. Nuclear AR immunostaining was decreased and
      apoptosis was increased, but cell proliferation remained largely unaffected in
      metastases within a few days after surgical castration. In CRPC patients, nuclear
      AR staining of metastases was increased when compared to short-term castrated
      patients. The nuclear AR staining score was related to tumour cell proliferation,
      but it was not associated with other downstream effects of AR activation such as
      apoptosis and PSA staining, and it was only marginally related to the presence of
      neuroendocrine tumour cells. Serum PSA at metastasis surgery, although related to
      outcome, was not associated with AR staining, markers of metastasis growth or PSA
      staining in metastases. High nuclear AR immunostaining was associated with a
      particularly poor prognosis after metastasis surgery in CRPC patients, suggesting
      that such men may benefit from the potent AR blockers now tested in clinical
      trials.

PMID- 20688882
TI  - Chronic kidney disease: an inherent risk factor for acute kidney injury?
AB  - Epidemiologic evidence suggests that chronic kidney disease (CKD) is a risk
      factor for acute kidney injury (AKI) due to the prevalence of CKD in patients who
      have episodes of AKI. However, the high burden of comorbidities such as age,
      diabetes, peripheral vascular, cardiovascular, and liver disease accompanying
      CKD, and the difficulties of defining AKI in the setting of CKD make these
      observations difficult to interpret. These comorbidities not only could alter the
      course of AKI but also may be the driving force behind the epidemiologic
      association between CKD and AKI because of systemic changes and/or increased
      exposure to potential nephrotoxic risks. Here, we contend that studies suggesting
      that CKD is a risk factor for AKI may suffer from residual confounding and
      reflect an overall susceptibility to illness rather than biologic susceptibility
      of the kidney parenchyma to injury. In support of our argument, we discuss the
      clinical evidence from epidemiologic studies, and the knowledge obtained from
      animal models on the pathophysiology of AKI and CKD, demonstrating a
      preconditioning influence of the previously impaired kidneys against subsequent
      injury. We conclude that, under careful analysis, factors apart from the inherent
      pathophysiology of the diseased kidney may be responsible for the increased
      frequency of AKI in CKD patients, and the impact of CKD on the risk and severity
      of AKI needs further investigation. Moreover, certain elements in the
      pathophysiology of a previously injured kidney may, surprisingly, bear out to be
      protective against AKI.

PMID- 20688883
TI  - Associations between serum leptin level and bone turnover in kidney transplant
      recipients.
AB  - BACKGROUND AND OBJECTIVES: Obesity is associated with increased parathyroid
      hormone (PTH) in the general population and in patients with chronic kidney
      disease (CKD). A direct effect of adipose tissue on bone turnover through leptin
      production has been suggested, but such an association has not been explored in
      kidney transplant recipients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This
      study examined associations of serum leptin with PTH and with biomarkers of bone
      turnover (serum beta crosslaps [CTX, a marker of bone resorption] and osteocalcin
      [OC, a marker of bone formation]) in 978 kidney transplant recipients.
      Associations were examined in multivariable regression models. Path analyses were
      used to determine if the association of leptin with bone turnover is independent
      of PTH. RESULTS: Higher leptin levels were associated with higher PTH and lower
      vitamin D levels, and adjustment for vitamin D attenuated the association between
      leptin and PTH. However, higher leptin was also significantly associated with
      lower levels of the bone turnover markers: 1 SD higher leptin was associated with
      0.13 lower log-OC (-0.17, -0.08, P < 0.001) and 0.030 lower log-CTX (-0.045, 
      0.016, P < 0.001) after multivariable adjustments. Path analysis indicated that
      the association of leptin with PTH was mostly mediated through vitamin D, and
      that the association between leptin and bone turnover was independent of PTH and
      vitamin D. CONCLUSIONS: Elevated leptin level is associated with lower bone
      turnover independent of its effects on serum PTH in kidney transplant recipients.

PMID- 20688884
TI  - Serum phosphate and mortality in patients with chronic kidney disease.
AB  - BACKGROUND AND OBJECTIVES: Higher phosphate is associated with mortality in
      dialysis patients but few prospective studies assess this in nondialysis patients
      managed in an outpatient nephrology clinic. This prospective longitudinal study
      examined whether phosphate level was associated with death in a referred
      population. DESIGN, SETTING, PARTICIPANTS & MEASUREMENTS: Patients (1203) of
      nondialysis chronic kidney disease (CKD) in the Chronic Renal Insufficiency
      Standards Implementation Study were assessed. Survival analyses were performed
      for quartiles of baseline phosphate relative to GFR, 12-month time-averaged
      phosphate, and baseline phosphate according to published phosphate targets.
      RESULTS: Mean (SD) eGFR was 32 (15) ml/min per 1.73 m(2), age 64 (14) years, and
      phosphate 1.2 (0.30) mmol/L. Cox multivariate adjusted regression in CKD stages 3
      to 4 patients showed an increased risk of all-cause and cardiovascular mortality
      in the highest quartile compared with that in the lowest quartile of phosphate.
      No association was found in CKD stage 5 patients. Patients who had values above
      recommended targets for phosphate control had increased risk of all-cause and
      cardiovascular death compared with patients below target. The highest quartile
      compared with the lowest quartile of 12-month time-averaged phosphate was
      associated with an increased risk of mortality. CONCLUSIONS: In CKD stages 3 to 4
      patients, higher phosphate was associated with a stepwise increase in mortality.
      As phosphate levels below published targets (as opposed to within them) are
      associated with better survival, guidelines for phosphate in nondialysis CKD
      patients should be re-examined. Intervention trials are required to determine
      whether lowering phosphate will improve survival.

PMID- 20688885
TI  - Message to the FDA on ESAs: REMS is not enough, more studies are needed.

PMID- 20688886
TI  - Discrepancy between Medical Evidence Form 2728 and renal biopsy for glomerular
      diseases.
AB  - BACKGROUND AND OBJECTIVES: The United States Renal Data System (USRDS) is a
      commonly utilized database for epidemiologic research of ESRD patients. USRDS
      uses Medical Evidence Form 2728 to collect medical information about ESRD
      patients. The validity of the Form 2728 "primary cause of renal failure" field
      for glomerular diseases has not been evaluated, although inconsistencies between
      Form 2728 information and medical records have been documented previously with
      respect to comorbidities. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Form
      2728 information was linked with renal biopsy results from the Glomerular Disease
      Collaborative Network (GDCN) for 217 patients with biopsy-confirmed glomerular
      diseases who had reached ESRD. Biopsy results were compared with the Form 2728
      "primary cause of renal failure" field. Diseases were considered individually,
      and also categorized into commonly used disease groups. Percentage of agreement
      and disease-specific measures of validity were calculated. RESULTS: Overall
      agreement between renal biopsy and Form 2728 was low (14.8% overall, 23.0% when
      categorized). Agreement was better after Form 2728 was revised in 1995 (10.0%
      before versus 23.2% after overall). The cause of ESRD field was left blank in 57%
      of the forms submitted for glomerular disease patients. Individual glomerular
      diseases had very low specificities, but tended to have high positive predictive
      values. CONCLUSIONS: Form 2728 does not accurately reflect the renal pathology
      diagnosis as captured by biopsy. The large degree of missing data and
      misclassification should be of concern to those performing epidemiologic research
      using Form 2728 information on glomerular diseases.

PMID- 20688887
TI  - A systematic review and meta-analysis of pregnancy outcomes in patients with
      systemic lupus erythematosus and lupus nephritis.
AB  - BACKGROUND AND OBJECTIVES: Studies of the impact of systemic lupus erythematosus
      (SLE) and its pregnancy complications have yielded conflicting results. Major
      limitations of these studies relate to their small numbers of patients and
      retrospective designs. The aim of this study was to perform a systematic
      literature review of pregnancy outcomes in women with SLE and a meta-analysis of
      the association of lupus nephritis with adverse pregnancy outcomes. DESIGN,
      SETTING, PARTICIPANTS, & MEASUREMENTS: We searched electronic databases from 1980
      to 2009 and reviewed papers with validity criteria. Random-effects analytical
      methods were used to evaluate pregnancy complications rates. RESULTS: Thirty
      seven studies with 1842 patients and 2751 pregnancies were included. Maternal
      complications included lupus flare (25.6%), hypertension (16.3%), nephritis
      (16.1%), pre-eclampsia (7.6%), and eclampsia (0.8%). The induced abortion rate
      was 5.9%, and when excluded, fetal complications included spontaneous abortion
      (16.0%), stillbirth (3.6%), neonatal deaths (2.5%), and intrauterine growth
      retardation (12.7%). The unsuccessful pregnancy rate was 23.4%, and the premature
      birth rate was 39.4%. Meta-regression analysis showed statistically significant
      positive associations between premature birth rate and active nephritis and
      increased hypertension rates in subjects with active nephritis or a history of
      nephritis. History of nephritis was also associated with pre-eclampsia. Anti
      phospholipid antibodies were associated with hypertension, premature birth, and
      an increased rate of induced abortion. CONCLUSIONS: In patients with SLE, both
      lupus nephritis and anti-phospholipid antibodies increase the risks for maternal
      hypertension and premature births. The presented evidence further supports timing
      of pregnancy relative to SLE activity and multispecialty care of these patients.

PMID- 20688888
TI  - Phylogeography of the Marine Otter (Lontra felina): historical and contemporary
      factors determining its distribution.
AB  - The evolutionary history of a species can be revealed by phylogeographical
      analysis; nevertheless, not only historical but also contemporary processes can
      imprint on the distribution of genetic diversity. We report on the phylogeny of
      Lontra ssp. in South America, and the role of spatial heterogeneity in shaping
      the distribution and population structure of the endangered marine otter, Lontra
      felina. Analyzing a total of 2261 bp of mitochondrial DNA (mtDNA) revealed the
      recent divergence of L. felina from L. provocax. A strong population structure
      (Phi(st) = 0.83, P < 0.0001) and a significant pattern of isolation by distance
      were described for L. felina (n = 168) across a wide geographical distribution
      (13 degrees 53'S to 43 degrees 36'S). Lontra felina mtDNA phylogeny is composed
      of 2 main clades: a clade from Peru and another composed of Chilean haplotypes.
      Northern populations show different divergent lineages and higher genetic
      diversity when compared with more recently colonized southern populations.
      Furthermore, long sandy beaches seem to act as barriers to dispersal, creating 2
      evolutionary significant units in agreement with subspecies previous description,
      and at least 5 different management units (MUs). At a fine spatial scale, the
      size of rocky seashore patches, the distance between patches and anthropogenic
      factors also play important roles in species gene flow.

PMID- 20688889
TI  - Natalizumab (Tysabri).
AB  - Natalizumab is a humanized IgG4kappa monoclonal antibody that is a selective
      adhesion molecule inhibitor, which prevents adhesion of leukocytes to endothelial
      cells. It is the first monoclonal antibody approved by the FDA for the treatment
      of relapsing-remitting MS. This article will review the mechanism of action and
      clinical role of this agent.

PMID- 20688890
TI  - What to do before pulmonary rehabilitation to improve adherence?

PMID- 20688891
TI  - The effect of airflow limitation on the cause of death in patients with COPD.
AB  - COPD is characterized by airflow limitation that is usually progressive. The
      present study investigated the cause of death and the effect of airflow
      limitation on all-cause mortality in COPD patients. A prospective cohort of 600
      COPD patients were followed for 3 years. Patients in the Global Initiative for
      Chronic Obstructive Lung Disease (GOLD) stage 2 (32.7%), GOLD 3 (48.1%), or GOLD
      4 (19.1%). Overall, 117 patients died (19.6%). Deaths were due to respiratory
      failure (29%), cardiovascular disease (25.6%), cancer (17.9%), infection (11%),
      gastrointestinal disease (9.4%), and other causes (6.7%). According to the Cox
      regression analysis, the following independent factors were related to mortality:
      age (years), hazards ratio (HR) 1.046 (confidence interval [CI] 95% 1.021,
      1.072); current smoking status, HR 1.535 (CI 95% 1.003, 2.350); cancer, HR 7.172
      (CI 95% 4.515, 11.395); cardiovascular disease, HR 2.623 (CI 95% 1.821, 3.778);
      severe airflow limitation (GOLD 4), HR 2.378 (CI 95% 1.605, 3.525); and highest
      quartile of acute exacerbations, HR 1.852 (CI 95% 1.236, 2.775). The present
      study shows that severe airflow limitation, current smoking status, the presence
      of cardiovascular disease, cancer, and a high frequency of acute exacerbations
      have an independent negative impact on the prognosis of COPD patients.

PMID- 20688893
TI  - Effectiveness of a group opt-in session on uptake and graduation rates for
      pulmonary rehabilitation.
AB  - Pulmonary rehabilitation (PR) is an effective intervention in the treatment of
      patients with chronic obstructive pulmonary disease (COPD). Unfortunately some
      patients offered this treatment either fail to take up the offer or fail to
      complete the course. Studies have indicated a number of factors influencing
      uptake and completion rates. We describe the introduction of an intervention, the
      group opt-in session (GOIS), prior to individualised baseline assessment and
      entry to the PR course, with the intention being to improve uptake and completion
      rates. A 1.5-hour-long GOIS was offered as the first face-to-face contact to all
      patients referred for PR. Drop-out rates at all stages of the pathway from
      referral to graduation were collected on 200 patients prior to the introduction
      of the GOIS (non-GOIS group) and compared to the first 400 patients following
      introduction (the GOIS group). Possible independent predictors of course uptake
      and completion were examined in the GOIS group. The proportion of referred
      patients taking up the offer of individualised baseline assessment or a GOIS was
      similar (75% vs. 72.2%, p value not significant [ns]). However, since in the GOIS
      group the opt-in session preceded the individualised baseline assessment and some
      patients opted-out, a smaller proportion of referred patients underwent this
      assessment than in the non-GOIS group (58.7% vs. 75%, p < 0.001). In addition,
      dropouts following individualised baseline assessments were also reduced (7% vs.
      22%, p < 0.001). Both of these factors reduced 'wasted' assessments. Similar
      proportions of patients referred began the PR course in both groups (53% vs.
      51.7%, ns), but a higher proportion of patients graduated in the GOIS group
      (87.9% vs. 76.4%, p < 0.05). Drop-out rates due to illness were similar in both
      groups (8.5% pre vs. 6.8% post, ns). However, drop-out rates not due to illness
      were much higher in the non-GOIS group (15.1% vs. 5.3%, p < 0.001). In the GOIS
      group, patients who did not attend the GOIS were, on average, younger (64.6 years
      vs. 69.7 years, p < 0.001) and had a higher mean percent predicted Forced
      Expiratory Volume (50.6% vs. 43.8%, p < 0.05) than those that did attend. A
      greater proportion of patients who opted in to the GOIS and attended the PR
      course lived less than 25 minutes from the PR centre than either those who did
      not attend the GOIS or who attended and then opted out (77.4% vs. 63%, p<0.005).
      The GOIS improved the graduation rates at The North Bristol Lung Centre PR Course
      and reduced wasted assessments. There was no effect on initial uptake. Analysis
      of the behaviour of patients invited to a GOIS suggested that age, lung function
      and travel distance were important factors influencing patient choice.

PMID- 20688892
TI  - Symptoms of anxiety and depression in COPD patients entering pulmonary
      rehabilitation.
AB  - Chronic obstructive pulmonary disease (COPD) patients may suffer from symptoms of
      anxiety and depression. Whether and to what extent symptoms of anxiety and
      depression may be present in COPD patients entering pulmonary rehabilitation and
      which patient characteristics are associated with psychological distress remains
      currently unknown. The objective of the present study is to determine the
      prevalence and the determinants of clinically relevant symptoms of anxiety and
      depression in COPD patients entering pulmonary rehabilitation. Symptoms of
      anxiety and depression have been assessed in 701 COPD patients entering pulmonary
      rehabilitation using the Hospital Anxiety and Depression Scale. Additionally,
      disease-specific health status, pulmonary function, body composition, exercise
      capacity, co-existing morbidities, smoking status, symptoms, long-term oxygen
      therapy and the use of antidepressant and anxiolytic drugs have been recorded.
      Patients had mean anxiety scores of 7.6 points and mean depression scores of 7.2
      points. Anxiety scores >or=10 points were present in 225 patients (32%) and
      depression scores >or=10 points were present in 192 patients (27%). Patients at
      risk of having symptoms of anxiety were female or used antidepressant or
      anxiolytic drugs. Patients at risk of having symptoms of depression experienced
      dyspnea, had a body mass index (BMI) <21 kg/m(2) or used antidepressant or
      anxiolytic drugs. A considerable proportion of the COPD patients entering
      pulmonary rehabilitation report symptoms of anxiety and/or depression, which may
      significantly impair disease-specific health status. Patients at risk of having
      symptoms of anxiety and/or depression are female, experience dyspnea, have a low
      BMI or use antidepressant and/or anxiolytic drugs.

PMID- 20688894
TI  - Respiratory muscle pressures in non-CF bronchiectasis: repeatability and
      reliability.
AB  - BACKGROUND: Respiratory muscle strength is used diagnostically in clinical
      practice and as an outcome measure in clinical trials in various chronic lung
      diseases. There is limited data on its repeatability in people with non-CF
      bronchiectasis. The aim of the present study was to assess the repeatability of
      maximal inspiratory (P( I)max) and expiratory pressures (P(E)max) in a group of
      patients with stable, moderate-to-severe non-CF bronchiectasis. METHODS: Twenty
      participants with stable moderate-to-severe non-CF bronchiectasis were recruited.
      Respiratory muscle strength measurements (three maximal inspiratory and
      expiratory pressures) were made on 2 separate days. A standard protocol was used,
      including practice tests, before obtaining three technically acceptable and
      reproducible readings with a difference of 10% or less between values. CLINICAL
      TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT00487149. RESULTS: The mean
      (SD) age of the non-CF bronchiectasis group was 63 (9) years. Maximal inspiratory
      pressures were repeatable with mean (SD) for highest P(I)max, Test 1 and Test 2,
      75.90 (20) and 79.40 (19) cmH(2)O, and limits of agreement (mean difference +/-
      2SD) -3.50 +/- 20 cmH(2)O, (p = 0.14). Maximal expiratory pressures differed
      significantly with mean (SD) for highest P(E)max, Test 1 and Test 2, 102.25 (27)
      and 112.30 (32) cmH(2)O, and limits of agreement (mean difference +/- 2SD) -10.10
      +/- 35 cmH(2)O, (p = 0.02). The intraclass correlation coefficient (95% CI) for
      highest P(I)max and P(E)max was 0.93 (95% CI 0.82 to 0.97) and 0.90 (95% CI 0.76
      to 0.96), respectively. CONCLUSION: Maximal inspiratory pressure measurements
      were repeatable during a period of clinical stability in moderate-to-severe non
      CF bronchiectasis, suggesting this may be a useful outcome measure in non-CF
      bronchiectasis. Once a baseline has been established, a second visit is not
      required. P(E)max was not a repeatable measure and further study is necessary to
      ascertain how much practice testing is required to obtain an accurate value.

PMID- 20688895
TI  - Differentiating between IPF and NSIP.
AB  - Of the idiopathic interstitial pneumonias, idiopathic pulmonary fibrosis (IPF)
      and nonspecific interstitial pneumonia (NSIP) have provoked the most debate and
      discussion. Although the two diseases are distinct entities, diagnosis is not
      always straightforward and requires a multidisciplinary approach, integrating
      clinical, radiological and histologic information. Although there is currently no
      effective treatment for either disease, the importance of differentiating NSIP
      from IPF lies in the management of the individual patient, with particular focus
      on outcome and pace of change, and enrollment into novel treatment trials of IPF.

PMID- 20688896
TI  - Relationship between cytokeratin staining patterns and clinico-pathological
      features in somatotropinomae.
AB  - OBJECTIVE: Somatotropinomae are classified as densely and sparsely granulated
      adenomae, which typically exhibit a perinuclear pattern (PP) and a dot pattern
      (DP) in cytokeratin (CK) immunostaining respectively. Some exhibit a mixed
      pattern (MP). We studied the relationship between these somatotropinoma subtypes
      and their clinico-pathological features. METHODS: The study population consisted
      of 141 Japanese acromegalic patients. We evaluated their clinical presentation
      and their response to provocation tests with TRH and LHRH and to suppression
      (octreotide) test. Tumour tissues were subjected to immunostaining for CAM-5.2,
      MIB-1, CD34, E-cadherin (CDH1) and p53 (TP53). In 43 cases (30 non-DP and 13 DP),
      we analysed gsp mutations (constitutively activating mutations of the G(s)alpha
      protein that is encoded by GNAS gene). RESULTS: The 141 adenomae were categorised
      into three subtypes based on their CK staining patterns; 30 (21.3%) exhibited DP,
      83 (58.9%) exhibited PP, and 28 (19.9%) exhibited MP. Compared with the other
      subtypes, DP adenomae were significantly larger, and their E-cadherin expression
      and response to TRH, LHRH and octreotide challenge were lower. The postoperative
      cure rate tended to be lower in DP adenomae. gsp mutations were detected in 25 of
      43 cases examined (58.1%); 20 of the 30 non-DP (66.7%) and 5 of the 13 DP tumours
      (38.5%) were affected by the mutation. CONCLUSION: DP somatotropinomae exhibit
      characteristic features. Compared with the non-DP subtypes, DP adenomae
      manifested a larger tumour size, a lower incidence of abnormal responses to TRH
      and LHRH challenge, a poor response to octreotide test and a lower expression of
      E-cadherin. gsp mutation was not exclusive for non-DP somatotropinomae.

PMID- 20688897
TI  - Upper airway obstruction in patients with endothoracic goiter enlargement: no
      relationship between flow-volume loops and radiological tests.
AB  - BACKGROUND: In about 16-85% of subjects with goiter, upper airway obstruction
      (UAO) is observed. This percentage is higher in patients affected by goiter with
      endothoracic enlargement. UAO is an indication for surgery. Visual analysis of
      flow-volume loops (FVL) are the best indicators for UAO, although various studies
      using clinical and radiological parameters have observed no correlation.
      OBJECTIVE: To evaluate the presence of UAO in patients with endothoracic goiter
      enlargement and the relationship between the FVL with the observed symptoms and
      the measurements obtained by computed tomography (CT). SUBJECTS: Subjects with
      endothoracic goiter enlargement participated in the study. DESIGN: i) Symptom
      questionnaire (dysphagia, dyspnea, cough, oppression, dysphonia, and worsened
      symptoms when prone); ii) analysis: TSH and free thyroxine; iii) cervical
      ultrasound; iv) cervical-thoracic CT (measurements of area and diameter in the
      area of maximum stenosis and at 2 cm from the carina); v) chest radiography and
      vi) forced spirometry: visual analysis of FVL morphology and the maximum forced
      expiratory volume in 1 s (FEV(1)), forced expiratory flow at 50% vital
      capacity/forced inspiratory flow at 50% vital capacity and FEV(1)/peak expiratory
      flow parameters. RESULTS: Fifty subjects participated in the study: 11 men/39
      women, median age 73.8 years (43.76-88.43). UAO was diagnosed in 13 cases (26%,
      confidence interval: 14.6-40.3%) and 27 subjects (54%) presented symptoms
      suggesting goiter compression. No clinical or radiological variables showed the
      presence of UAO. CONCLUSIONS: The frequency of UAO in subjects affected by goiter
      with endothoracic enlargement was lower than that described for goiter patients,
      and there were no clinical or radiological indicators to establish its presence.

PMID- 20688899
TI  - The emergence of translational epidemiology: from scientific discovery to
      population health impact.
AB  - Recent emphasis on translational research (TR) is highlighting the role of
      epidemiology in translating scientific discoveries into population health impact.
      The authors present applications of epidemiology in TR through 4 phases
      designated T1-T4, illustrated by examples from human genomics. In T1,
      epidemiology explores the role of a basic scientific discovery (e.g., a disease
      risk factor or biomarker) in developing a "candidate application" for use in
      practice (e.g., a test used to guide interventions). In T2, epidemiology can help
      to evaluate the efficacy of a candidate application by using observational
      studies and randomized controlled trials. In T3, epidemiology can help to assess
      facilitators and barriers for uptake and implementation of candidate applications
      in practice. In T4, epidemiology can help to assess the impact of using candidate
      applications on population health outcomes. Epidemiology also has a leading role
      in knowledge synthesis, especially using quantitative methods (e.g., meta
      analysis). To explore the emergence of TR in epidemiology, the authors compared
      articles published in selected issues of the Journal in 1999 and 2009. The
      proportion of articles identified as translational doubled from 16% (11/69) in
      1999 to 33% (22/66) in 2009 (P = 0.02). Epidemiology is increasingly recognized
      as an important component of TR. By quantifying and integrating knowledge across
      disciplines, epidemiology provides crucial methods and tools for TR.

PMID- 20688898
TI  - Wnt/beta-catenin signaling in T-cell immunity and cancer immunotherapy.
AB  - Wnt ligands are lipid-modified secreted glycoproteins that regulate embryonic
      development, cell fate specification, and the homeostasis of self-renewing adult
      tissues. In addition to its well-established role in thymocyte development,
      recent studies have indicated that Wnt/beta-catenin signaling is critical for the
      differentiation, polarization, and survival of mature T lymphocytes. Here, we
      describe our current understanding of Wnt signaling in the biology of post-thymic
      T cells, and discuss how harnessing the Wnt/beta-catenin pathway might improve
      the efficacy of vaccines, T-cell-based therapies, and allogeneic stem cell
      transplantation for the treatment of patients with cancer.

PMID- 20688901
TI  - Invited commentary: The epicenter of translational science.
AB  - Epidemiology is at the center of translational science. Uniquely among biomedical
      disciplines, the methods and perspective of epidemiology span research from
      discovery to effective interventions and ultimately to their dissemination and
      implementation. However, shorthand designations for various phases of
      translational science, such as "T1, T2, T3, and T4," may be proliferating past
      the level of their usefulness. It is worthwhile to reflect on the actual nature
      of the science undertaken by epidemiologists along the continuum of discovery to
      application. The new challenge for epidemiology is the integration of knowledge
      and effective interventions into various societal settings working with allied
      disciplines not necessarily in the biomedical domain to ensure that these
      interventions have their intended effects on individual and public health.

PMID- 20688900
TI  - A study of the birth weight-obesity relation using a longitudinal cohort and
      sibling and twin pairs.
AB  - Sibling and twin study designs provide control for confounding factors that are
      typically unmeasured in traditional cohort studies. Using nationally
      representative data from the National Longitudinal Study of Adolescent Health
      collected at 3 visits during 1994-2002, the authors evaluated the longitudinal
      association between birth weight and later obesity in a traditional cohort study
      (n = 13,763; ages 11-21 years at baseline), controlling for sex, age,
      race/ethnicity, and parental education. Among persons with a nonobese mother,
      high birth weight (>4 kg) participants were more likely than normal birth weight
      (>/=2.5-</=4 kg) participants to become obese later in life (incidence rate ratio
      = 1.46, 95% confidence interval: 1.28, 1.67). In a matched sibling pair sample
      (full siblings: n = 513; monozygotic twins: n = 207; dizygotic twins: n = 189),
      the authors examined longitudinal within-pair differences. Birth weight
      difference was positively associated with body mass index difference later in
      life for female monozygotic pairs only (beta = 2.67, 95% confidence interval:
      0.99, 4.35). Given the null associations observed in the sibling sample, the
      commonly observed positive association between birth weight and later obesity
      from cohort analyses may be attributed to confounding by maternal
      characteristics. Further research is needed to identify specific factors that
      contribute to the birth weight-obesity relation.

PMID- 20688902
TI  - Re: "Alcohol consumption in young adults and incident hypertension: 20-year
      follow-up from the Coronary Artery Risk Development in Young Adults Study".

PMID- 20688904
TI  - Risk of incident cardiovascular disease among users of smokeless tobacco in the
      Atherosclerosis Risk in Communities (ARIC) study.
AB  - Use of smokeless tobacco in the United States has been relatively constant in
      recent years, as tobacco companies continue aggressive marketing campaigns. The
      health effects of smokeless tobacco use need further documentation. Thus, the
      authors examined whether current use of smokeless tobacco was associated with
      increased incidence of cardiovascular disease (CVD) in 14,498 men and women aged
      45-64 years at baseline (1987-1989) in the Atherosclerosis Risk in Communities
      (ARIC) Study. There were 2,572 incident CVD events (myocardial infarction,
      coronary revascularization, coronary death, or stroke) during a median of 16.7
      years of follow-up (maximum = 19.1 years). Current use of smokeless tobacco at
      baseline was associated with 1.27-fold greater CVD incidence (95% confidence
      interval: 1.06, 1.52) than was nonuse, independently of demographic,
      socioeconomic, and lifestyle and other tobacco-related variables. Past use of
      smokeless tobacco was not associated with CVD incidence. In conclusion, current
      use of smokeless tobacco was associated with increased risk of CVD incidence in
      ARIC cigarette nonsmokers. Current users of smokeless tobacco should be informed
      of its harm and advised to quit the practice. Current cigarette smokers should
      also be given sufficient information on safe, therapeutic methods of quitting
      which do not include switching to smokeless tobacco.

PMID- 20688905
TI  - Use of aspirin and other nonsteroidal antiinflammatory medications in relation to
      prostate cancer risk.
AB  - Recent interest has focused on the role that inflammation may play in the
      development of prostate cancer and whether use of aspirin or other nonsteroidal
      antiinflammatory drugs (NSAIDs) affects risk. In a population-based case-control
      study designed to investigate the relation between these medications and prostate
      cancer risk, detailed exposure data were analyzed from 1,001 cases diagnosed with
      prostate cancer between January 1, 2002, and December 31, 2005, and 942 age
      matched controls from King County, Washington. A significant 21% reduction in the
      risk of prostate cancer was observed among current users of aspirin compared with
      nonusers (95% confidence interval (CI): 0.65, 0.96). Long-term use of aspirin (>5
      years: odds ratio = 0.76, 95% CI: 0.61, 0.96) and daily use of low-dose aspirin
      (odds ratio = 0.71, 95% CI: 0.56, 0.90) were also associated with decreased risk.
      There was no evidence that the association with aspirin use varied by disease
      aggressiveness, but there was effect modification (P(interaction) = 0.02) with a
      genetic variant in prostaglandin-endoperoxide synthase 2 (PTGS2) (rs12042763).
      Prostate cancer risk was not related to use of either nonaspirin NSAIDs or
      acetaminophen. These results contribute further evidence that aspirin may have
      chemopreventive activity against prostate cancer and highlight the need for
      additional research.

PMID- 20688906
TI  - Probabilistic (Bayesian) modeling of gene expression in transplant
      glomerulopathy.
AB  - Transplant glomerulopathy (TG) is associated with rapid decline in glomerular
      filtration rate and poor outcome. We used low-density arrays with a novel
      probabilistic analysis to characterize relationships between gene transcripts and
      the development of TG in allograft recipients. Retrospective review identified TG
      in 10.8% of 963 core biopsies from 166 patients; patients with stable function
      were studied for comparison. The biopsies were analyzed for expression of 87
      genes related to immune function and fibrosis by using real-time PCR, and a
      Bayesian model was generated and validated to predict histopathology based on
      gene expression. A total of 57 individual genes were increased in TG compared
      with stable function biopsies (P < 0.05). The Bayesian analysis identified
      critical relationships between ICAM-1, IL-10, CCL3, CD86, VCAM-1, MMP-9, MMP-7,
      and LAMC2 and allograft pathology. Moreover, Bayesian models predicted TG when
      derived from either immune function (area under the curve [95% confidence
      interval] of 0.875 [0.675 to 0.999], P = 0.004) or fibrosis (area under the curve
      [95% confidence interval] of 0.859 [0.754 to 0.963], P < 0.001) gene networks.
      Critical pathways in the Bayesian models were also analyzed by using the Fisher
      exact test and had P values <0.005. This study demonstrates that evaluating
      quantitative gene expression profiles with Bayesian modeling can identify
      significant transcriptional associations that have the potential to support the
      diagnostic capability of allograft histology. This integrated approach has broad
      implications in the field of transplant diagnostics.

PMID- 20688907
TI  - A novel method of amplification of FFPET-derived RNA enables accurate disease
      classification with microarrays.
AB  - A new method for amplification and labeling of RNA is assessed that permits gene
      expression microarray analysis of formalin-fixed paraffin-embedded tissue (FFPET)
      samples. Valid biological data were obtained using gene expression microarrays of
      diffuse large B-cell lymphoma (DLBCL) FFPET samples. We examined 59 matched DLBCL
      patient samples, FFPET, and fresh/frozen. The samples contained both prognostic
      subgroups of DLBCL: germinal center B-cell (GCB) and activated B-cell (ABC).
      Fresh/frozen (FF) samples were amplified by both the traditional Eberwine oligo
      dT method and a new method described herein. The matching FFPET samples were also
      amplified using the new method. Here we detail the comparison of results from all
      three datasets of matched samples. An established classification model built from
      previous data accurately classified these new samples. This new method provides a
      useful technology advance for microarray analysis of FFPET archival samples.

PMID- 20688908
TI  - Diagnostic testing for pandemic influenza in Singapore: a novel dual-gene
      quantitative real-time RT-PCR for the detection of influenza A/H1N1/2009.
AB  - With the relative global lack of immunity to the pandemic influenza A/H1N1/2009
      virus that emerged in April 2009 as well as the sustained susceptibility to
      infection, rapid and accurate diagnostic assays are essential to detect this
      novel influenza A variant. Among the molecular diagnostic methods that have been
      developed to date, most are in tandem monoplex assays targeting either different
      regions of a single viral gene segment or different viral gene segments. We
      describe a dual-gene (duplex) quantitative real-time RT-PCR method selectively
      targeting pandemic influenza A/H1N1/2009. The assay design includes a primer
      probe set specific to only the hemagglutinin (HA) gene of this novel influenza A
      variant and a second set capable of detecting the nucleoprotein (NP) gene of all
      swine-origin influenza A virus. In silico analysis of the specific HA
      oligonucleotide sequence used in the assay showed that it targeted only the swine
      origin pandemic strain; there was also no cross-reactivity against a wide
      spectrum of noninfluenza respiratory viruses. The assay has a diagnostic
      sensitivity and specificity of 97.7% and 100%, respectively, a lower detection
      limit of 50 viral gene copies/PCR, and can be adapted to either a qualitative or
      quantitative mode. It was first applied to 3512 patients with influenza-like
      illnesses at a tertiary hospital in Singapore, during the containment phase of
      the pandemic (May to July 2009).

PMID- 20688909
TI  - Bacterial macroscopic rope-like fibers with cytopathic and adhesive properties.
AB  - We present a body of ultrastructural, biochemical, and genetic evidence that
      demonstrates the oligomerization of virulence-associated autotransporter proteins
      EspC or EspP produced by deadly human pathogens enterohemorrhagic and
      enteropathogenic Escherichia coli into novel macroscopic rope-like structures (>1
      cm long). The rope-like structures showed high aggregation and insolubility,
      stability to anionic detergents and high temperature, and binding to Congo Red
      and thioflavin T dyes. These are properties also exhibited by human amyloidogenic
      proteins. These macroscopic ropes were not observed in cultures of nonpathogenic
      Escherichia coli or isogenic espP or espC deletion mutants of enterohemorrhagic
      or enteropathogenic Escherichia coli but were produced by an Escherichia coli K
      12 strain carrying a plasmid expressing espP. Purified recombinant EspP monomers
      were able to self-assemble into macroscopic ropes upon incubation, suggesting
      that no other protein was required for assembly. The ropes bound to and showed
      cytopathic effects on cultured epithelial cells, served as a substratum for
      bacterial adherence and biofilm formation, and protected bacteria from
      antimicrobial compounds. We hypothesize that these ropes play a biologically
      significant role in the survival and pathogenic scheme of these organisms.

PMID- 20688910
TI  - Exon-skipping splice variants of excitatory amino acid transporter-2 (EAAT2) form
      heteromeric complexes with full-length EAAT2.
AB  - The glial transporter excitatory amino acid transporter-2 (EAAT2) is the main
      mediator of glutamate clearance in brain. The wild-type transporter (EAAT2wt)
      forms trimeric membrane complexes in which each protomer functions autonomously.
      Several EAAT2 variants are found in control and Alzheimer-diseased human brains;
      their expression increases with pathological severity. These variants might alter
      EAAT2wt-mediated transport by abrogating membrane trafficking, or by changing the
      configuration or functionality of the assembled transporter complex. HEK293 cells
      were transfected with EAAT2wt; EAAT2b, a C-terminal variant; or either of two
      exon-skipping variants: alone or in combination. Surface biotinylation studies
      showed that only the exon-7 deletion variant was not trafficked to the membrane
      when transfected alone, and that all variants could reach the membrane when co
      transfected with EAAT2wt. Fluorescence resonance energy transfer (FRET) studies
      showed that co-transfected EAAT2wt and EAAT2 splice variants were expressed in
      close proximity. Glutamate transporter function was measured using a whole cell
      patch clamp technique, or by changes in membrane potential indexed by a voltage
      sensitive fluorescent dye (FMP assay): the two methods gave comparable results.
      Cells transfected with EAAT2wt or EAAT2b showed glutamate-dependent membrane
      potential changes consistent with functional expression. Cells transfected with
      EAAT2 exon-skipping variants alone gave no response to glutamate. Co-transfection
      of EAAT2wt (or EAAT2b) and splice variants in various ratios significantly raised
      glutamate EC(50) and decreased Hill coefficients. We conclude that exon-skipping
      variants form heteromeric complexes with EAAT2wt or EAAT2b that traffic to the
      membrane but show reduced glutamate-dependent activity. This could allow
      glutamate to accumulate extracellularly and promote excitotoxicity.

PMID- 20688911
TI  - Uptake of selenite by Saccharomyces cerevisiae involves the high and low affinity
      orthophosphate transporters.
AB  - Although the general cytotoxicity of selenite is well established, the mechanism
      by which this compound crosses cellular membranes is still unknown. Here, we show
      that in Saccharomyces cerevisiae, the transport system used opportunistically by
      selenite depends on the phosphate concentration in the growth medium. Both the
      high and low affinity phosphate transporters are involved in selenite uptake.
      When cells are grown at low P(i) concentrations, the high affinity phosphate
      transporter Pho84p is the major contributor to selenite uptake. When phosphate is
      abundant, selenite is internalized through the low affinity P(i) transporters
      (Pho87p, Pho90p, and Pho91p). Accordingly, inactivation of the high affinity
      phosphate transporter Pho84p results in increased resistance to selenite and
      reduced uptake in low P(i) medium, whereas deletion of SPL2, a negative regulator
      of low affinity phosphate uptake, results in exacerbated sensitivity to selenite.
      Measurements of the kinetic parameters for selenite and phosphate uptake
      demonstrate that there is a competition between phosphate and selenite ions for
      both P(i) transport systems. In addition, our results indicate that Pho84p is
      very selective for phosphate as compared with selenite, whereas the low affinity
      transporters discriminate less efficiently between the two ions. The properties
      of phosphate and selenite transport enable us to propose an explanation to the
      paradoxical increase of selenite toxicity when phosphate concentration in the
      growth medium is raised above 1 mm.

PMID- 20688912
TI  - Membrane cholesterol modulates the outward facing conformation of the dopamine
      transporter and alters cocaine binding.
AB  - Clearance of synaptically released dopamine is regulated by the plasmalemmal
      dopamine transporter (DAT), an integral membrane protein that resides within a
      complex lipid milieu. Here we demonstrate that cholesterol, a major component of
      the lipid bilayer, can modulate the conformation of DAT and alter cocaine binding
      to DAT. In striatal synaptosomes and transfected cells, DAT was in cholesterol
      rich membrane fractions after mild detergent extraction. After increasing the
      membrane cholesterol content by treatment of water-soluble cholesterol
      (cholesterol mixed with methyl-beta-cyclodextrin), we observed an increase in DAT
      binding B(max) values for cocaine analogs [(3)H]WIN35428 and [(125)I]RTI-55, but
      similar levels of DAT proteins on the cell surface were shown by surface
      biotinylation assays. Membrane cholesterol addition also markedly enhanced the
      accessibility of cysteine sulfhydryl moieties in DAT as probed by a membrane
      impermeable maleimide-biotin conjugate. We identified cysteine 306, a
      juxtamembrane residue on transmembrane domain 6 (TM6) of DAT, as the intrinsic
      residue exhibiting enhanced reactivity. Similar effects on DAT cysteine
      accessibility and radioligand binding were observed with addition of zinc, a
      reagent known to promote the outward facing conformation of DAT. Using
      substituted cysteine mutants on various positions likely to be extracellular, we
      identified additional residues located on TM1, TM6, TM7, and TM12 of DAT that are
      sensitive to alterations in the membrane cholesterol content. Our findings in
      transfected cells and native tissues support the hypothesis that DAT adopts an
      outward facing conformation in a cholesterol-rich membrane environment,
      suggesting a novel modulatory role of the surrounding membrane lipid milieu on
      DAT function.

PMID- 20688913
TI  - ATP binding to Hsp90 is sufficient for effective chaperoning of p53 protein.
AB  - Hsp90 is a ubiquitous, ATP-dependent chaperone, essential for eukaryotes. It
      possesses a broad spectrum of substrates, among which is the p53 transcription
      factor, encoded by a tumor-suppressor gene. Here, we elucidate the role of the
      adenine nucleotide in the Hsp90 chaperone cycle, by taking advantage of a unique
      in vitro assay measuring Hsp90-dependent p53 binding to the promoter sequence.
      E42A and D88N Hsp90beta variants bind but do not hydrolyze ATP, whereas E42A has
      increased and D88N decreased ATP affinity, compared with WT Hsp90beta.
      Nevertheless, both of these mutants interact with WT p53 with a similar affinity.
      Surprisingly, in the case of WT, but also E42A Hsp90beta, the presence of ATP
      stimulates dissociation of Hsp90-p53 complexes and results in p53 binding to the
      promoter sequence. D88N Hsp90beta is not efficient in both of these reactions.
      Using a trap version of the chaperonin GroEL, which irreversibly captures
      unfolded proteins, we show that Hsp90 chaperone action on WT p53 results in a
      partial unfolding of the substrate. The ATP-dependent dissociation of p53-Hsp90
      complex allows further folding of p53 protein to an active conformation, able to
      bind to the promoter sequence. Furthermore, in support of these results, the
      overproduction of WT or E42A Hsp90beta stimulates transcription from the WAF1
      gene promoter in H1299 cells. Altogether, our research indicates that ATP binding
      to Hsp90beta is a sufficient step for effective WT p53 client protein
      chaperoning.

PMID- 20688914
TI  - AMPK-dependent repression of hepatic gluconeogenesis via disruption of CREB.CRTC2
      complex by orphan nuclear receptor small heterodimer partner.
AB  - Orphan nuclear receptor small heterodimer partner (SHP) plays a key role in
      transcriptional repression of gluconeogenic enzyme gene expression. Here, we show
      that SHP inhibited protein kinase A-mediated transcriptional activity of cAMP
      response element-binding protein (CREB), a major regulator of glucose metabolism,
      to modulate hepatic gluconeogenic gene expression. Deletion analysis of
      phosphoenolpyruvate carboxykinase (PEPCK) promoter demonstrated that SHP
      inhibited forskolin-mediated induction of PEPCK gene transcription via inhibition
      of CREB transcriptional activity. In vivo imaging demonstrated that SHP inhibited
      CREB-regulated transcription coactivator 2 (CRTC2)-mediated cAMP-response element
      driven promoter activity. Furthermore, overexpression of SHP using adenovirus SHP
      decreased CRTC2-dependent elevations in blood glucose levels and PEPCK or glucose
      6-phosphatase (G6Pase) expression in mice. SHP and CREB physically interacted and
      were co-localized in vivo. Importantly, SHP inhibited both wild type CRTC2 and
      S171A (constitutively active form of CRTC2) coactivator activity and disrupted
      CRTC2 recruitment on the PEPCK gene promoter. In addition, metformin or
      overexpression of a constitutively active form of AMPK (Ad-CA-AMPK) inhibited
      S171A-mediated PEPCK and G6Pase gene expression, and hepatic glucose production
      and knockdown of SHP partially relieved the metformin- and Ad-CA-AMPK-mediated
      repression of hepatic gluconeogenic enzyme gene expression in primary rat
      hepatocytes. In conclusion, our results suggest that a delayed effect of
      metformin-mediated induction of SHP gene expression inhibits CREB-dependent
      hepatic gluconeogenesis.

PMID- 20688915
TI  - Rat and Drosophila synaptotagmin 4 have opposite effects during SNARE-catalyzed
      membrane fusion.
AB  - Synaptotagmins (Syt) are a large family of proteins that regulate membrane
      traffic in neurons and other cell types. One isoform that has received
      considerable attention is SYT4, with apparently contradictory reports concerning
      the function of this isoform in fruit flies and mice. SYT4 was reported to
      function as a negative regulator of neurotrophin secretion in mouse neurons and
      as a positive regulator of secretion of a yet to be identified growth factor from
      muscle cells in flies. Here, we have directly compared the biochemical and
      functional properties of rat and fly SYT4. We report that rat SYT4 inhibited
      SNARE-catalyzed membrane fusion in both the absence and presence of Ca(2+). In
      marked contrast, fly SYT4 stimulated SNARE-mediated membrane fusion in response
      to Ca(2+). Analysis of chimeric molecules, isolated C2 domains, and point mutants
      revealed that the C2B domain of the fly protein senses Ca(2+) and is sufficient
      to stimulate fusion. Rat SYT4 was able to stimulate fusion in response to Ca(2+)
      when the conserved Asp-to-Ser Ca(2+) ligand substitution in its C2A domain was
      reversed. In summary, rat SYT4 serves as an inhibitory isoform, whereas fly SYT4
      is a bona fide Ca(2+) sensor capable of coupling Ca(2+) to membrane fusion.

PMID- 20688916
TI  - A novel mechanism for ribonuclease regulation: transfer-messenger RNA (tmRNA) and
      its associated protein SmpB regulate the stability of RNase R.
AB  - The amount of RNase R, an important degradative exoribonuclease, increases 3-10
      fold under a variety of stress conditions. This elevation is due to
      posttranslational regulation in which the highly unstable RNase R protein becomes
      stabilized during stress. Here we identify two components of the trans
      translation machinery, transfer-messenger RNA (tmRNA) and SmpB, that are
      responsible for the short half-life of RNase R in exponential phase cells. The
      absence of either lengthens the half-life of RNase R in vivo >6-fold. SmpB
      directly interacts with RNase R in vitro and is stimulated by tmRNA. The C
      terminal region of RNase R, encompassing its basic region and adjacent S1 domain
      are required for the interaction; their removal eliminates binding and stabilizes
      RNase R in vivo. However, the binding of SmpB and tmRNA does not alter RNase R
      activity. These data define a previously unknown regulatory process in which the
      stability of an RNase is determined by its interaction with an RNA and an RNA
      associated protein.

PMID- 20688917
TI  - Molecular basis for recognition of nucleoside triphosphate by gene 4 helicase of
      bacteriophage T7.
AB  - The translocation of DNA helicases on single-stranded DNA and the unwinding of
      double-stranded DNA are fueled by the hydrolysis of nucleoside triphosphates
      (NTP). Although most helicases use ATP in these processes, the DNA helicase
      encoded by gene 4 of bacteriophage T7 uses dTTP most efficiently. To identify the
      structural requirements of the NTP, we determined the efficiency of DNA unwinding
      by T7 helicase using a variety of NTPs and their analogs. The 5-methyl group of
      thymine was critical for the efficient unwinding of DNA, although the presence of
      a 3'-ribosyl hydroxyl group partially overcame this requirement. The NTP-binding
      pocket of the protein was examined by randomly substituting amino acids for
      several amino acid residues (Thr-320, Arg-504, Tyr-535, and Leu-542) that the
      crystal structure suggests interact with the nucleotide. Although positions 320
      and 542 required aliphatic residues of the appropriate size, an aromatic side
      chain was necessary at position 535 to stabilize NTP for efficient unwinding. A
      basic side chain of residue 504 was essential to interact with the 4-carbonyl of
      the thymine base of dTTP. Replacement of this residue with a small aliphatic
      residue allowed the accommodation of other NTPs, resulting in the preferential
      use of dATP and the use of dCTP, a nucleotide not normally used. Results from
      this study suggest that the NTP must be stabilized by specific interactions
      within the NTP-binding site of the protein to achieve efficient hydrolysis. These
      interactions dictate NTP specificity.

PMID- 20688918
TI  - Regulation of the tyrosine kinase Pyk2 by calcium is through production of
      reactive oxygen species in cytotoxic T lymphocytes.
AB  - Pyk2 was identified as a Ca(2+)-dependent kinase, however, the regulation of Pyk2
      by Ca(2+) in T cells remains controversial. We found that Ca(2+) mobilization
      preferentially induced Pyk2 phosphorylation in cytotoxic T lymphocytes (CTL).
      Furthermore, Pyk2 phosphorylation in CTL was not absolutely Ca(2+) dependent but
      relied on the strength of T cell receptor stimulation. Ionomycin-stimulated Pyk2
      phosphorylation did not require calmodulin activity, because phosphorylation was
      not inhibited by the calmodulin inhibitor W7, and we detected no Ca(2+)-regulated
      association between Pyk2 and calmodulin. Ca(2+)-stimulated Pyk2 phosphorylation
      was dependent on Src-family kinase activity, even at the Pyk2 autophosphorylation
      site. We sought to identify a Ca(2+)-regulated pathway that could trigger Pyk2
      phosphorylation in T cells and found that ionomycin stimulated the production of
      reactive oxygen species and an H(2)O(2) scavenger inhibited ionomycin-induced
      Pyk2 phosphorylation. Additionally, H(2)O(2) induced strong Erk activation and
      ionomycin-stimulated Pyk2 phosphorylation was Erk dependent. These data support
      the conclusion that Ca(2+) mobilization induces the production of reactive oxygen
      species, which in turn activate the Erk pathway, leading to Src-family kinase
      dependent Pyk2 phosphorylation. Our data demonstrate that Pyk2 is not a Ca(2+)
      dependent kinase in T cells but instead, increased intracellular Ca(2+) induces
      Pyk2 phosphorylation through production of reactive oxygen species. These
      findings are consistent with the possibility that Pyk2 acts as an early sensor of
      numerous extracellular signals that trigger a Ca(2+) flux and/or reactive oxygen
      species to amplify tyrosine phosphorylation signaling events.

PMID- 20688919
TI  - Decreased exercise-induced expression of nuclear factor-kappaB-regulated genes in
      muscle of patients with COPD.
AB  - BACKGROUND: Nuclear factor (NF)-kappaB activation and oxidative stress are
      physiologic responses of skeletal muscle to exercise but may be impaired in
      patients with COPD. Therefore, we investigated NF-kappaB activity and expression
      of NF-kappaB-regulated genes in muscle of patients with COPD and control subjects
      before and after exercise. METHODS: Quadriceps specimens were obtained before,
      immediately after, and 2 h after a submaximal cycle ergometry test from seven
      patients with COPD (50.6 +/- 5.7 SEM FEV(1) of patients with COPD) and seven age
      matched control subjects. NF-kappaB DNA-binding activity in muscle and peripheral
      blood mononuclear cells (PBMCs) was determined using electrophoretic mobility
      shift assay and enzyme-linked immunosorbent assay, respectively. mRNA expression
      and protein carbonylation were measured by real-time polymerase chain reaction
      and Western blot, respectively. RESULTS: In control subjects, IL-6, IkappaBalpha,
      tumor necrosis factor-alpha, IL-1beta, superoxide dismutase, thioredoxin, heme
      oxygenase 1, and heat shock protein-70 were upregulated in muscle after exercise,
      whereas in patients with COPD only IL-6 mRNA was increased. Exercise-induced
      antiapoptotic Bcl2 mRNA levels were attenuated in patients with COPD compared
      with control subjects. Basal muscle protein oxidation was higher in patients with
      COPD than in control subjects, but attenuated in response to exercise. No
      exercise-induced changes in NF-kappaB DNA-binding activity in muscle and PBMCs of
      either group were detected. CONCLUSIONS: Skeletal muscle of patients with COPD is
      characterized by an impaired response to exercise of NF-kappaB-regulated genes
      encoding inflammatory cytokines, antioxidants, stress proteins, and survival
      factors.

PMID- 20688920
TI  - Only severely limited, premorbid functional status is associated with short- and
      long-term mortality in patients with pneumonia who are critically ill: a
      prospective observational study.
AB  - BACKGROUND: Severe pneumonia requiring ICU admission has not been well
      characterized with respect to long-term outcomes or predictors thereof. We
      examined the association between premorbid functional status and mortality in
      patients with severe pneumonia. METHODS: From 2000 to 2002, a population-based
      cohort of adults with pneumonia who were critically ill was enrolled and
      prospectively followed. Short-term (30-day) and long-term (1-year) mortality were
      examined using multivariable Cox regression models. RESULTS: The final cohort
      included 271 patients, mean age 61 years, 59% men, and 16% from nursing homes.
      The mean Pneumonia Severity Index was 113 (71% class IV or V), and the mean Acute
      Physiology and Chronic Health Evaluation II score was 17. Overall, 121 (45%)
      patients were functionally independent, 115 (42%) had limited mobility, and 35
      (13%) were completely dependent. Mortality was 11% at 30 days and 27% at 1 year;
      by functional status mortality was 6% at 30 days and 17% at 1 year for patients
      who were independent, 10% and 31% for patients with limited mobility, and 39% and
      48% for patients who were dependent. Mortality was greater for patients who were
      completely dependent when compared with patients who were independent (adjusted
      hazard ratio [aHR], 5.3; 95% CI, 2.0-14.1; P < .001 at 30 days; and aHR, 3.0; 95%
      CI, 1.5-6.1; P = .002 at 1 year) or with patients who had limited mobility (aHR,
      4.8; 95% CI, 2.0-11.2, P < .001 at 30 days; and aHR, 2.3; 95% CI, 1.3-4,4, P =
      .007 at 1 year). There were no mortality differences between patients with
      limited mobility and patients who were independent. CONCLUSIONS: One-quarter of
      patients with pneumonia who are critically ill are dead within 1 year. Severely
      limited premorbid functional status was associated with mortality; this should be
      considered at presentation for prognosis and at discharge for targeted follow-up.

PMID- 20688921
TI  - Chest tube drainage of transudative pleural effusions hastens liberation from
      mechanical ventilation.
AB  - BACKGROUND: Pleural effusions occur frequently in patients requiring mechanical
      ventilatory support. Treatment of the precipitating cause and resolution of the
      pleural effusion may take considerable time. We retrospectively studied the
      effect of chest tube drainage of transudative pleural effusions on the liberation
      of patients from mechanical ventilatory support. METHODS: Patients in the medical
      ICU (MICU) at Maimonides Medical Center between January 1, 2009, and October 31,
      2009, requiring mechanical ventilatory support with a transudative pleural
      effusion, were studied retrospectively. They were divided into two groups:
      standard care and standard care plus chest tube drainage. Chest tubes were placed
      under ultrasound guidance by trained intensivists. Duration of mechanical
      ventilatory support was the primary end point. Secondary end points included
      measures of oxygenation, amount of fluid drained, and complications associated
      with the chest tube. RESULTS: A total of 168 patients were studied; 88 were
      treated with standard care and 80 underwent chest tube drainage. Total duration
      of mechanical ventilatory support was significantly shorter for patients who had
      chest tube drainage: 3.8+/-0.5 days vs 6.5+/-1.1 days for the standard group
      (P=.03). No differences in oxygenation were noted between the two groups. The
      average amount of fluid drained was 1,220 mL. No significant complications were
      caused by chest tube drainage. CONCLUSIONS: Chest tube drainage of transudative
      pleural effusions resulted in more rapid liberation from mechanical ventilatory
      support. It is a very safe procedure when performed under ultrasound guidance by
      experienced personnel. TRIAL REGISTRY: ClinicalTrials.gov; Identifier:
      NCT0114285; URL: www.clinicaltrials.gov.

PMID- 20688922
TI  - Mannose-binding lectin gene polymorphism contributes to recurrence of infective
      exacerbation in patients with COPD.
AB  - BACKGROUND: Mannose-binding lectin (MBL) deficiency is associated with
      susceptibility to respiratory infections. We investigated the impact of MBL2 gene
      polymorphisms and MBL deficiency on the recurrence of infective exacerbation in
      patients with COPD. METHODS: A prospective study was conducted among 215 patients
      with COPD and 137 healthy subjects. MBL deficiency was determined by the MBL2
      gene polymorphisms and serum levels of MBL. RESULTS: The average frequency of
      infective exacerbations over 3 years in the 215 patients with COPD was 2.5 +/-
      1.3 episodes. The COPD group with three or more episodes of infective
      exacerbation (recurrent exacerbators) included 96 patients, and the remaining 119
      patients had two or fewer episodes (less-frequent exacerbators). Among the 96
      recurrent exacerbators, 12 (12.50%) had the MBL deficiency genotype compared with
      5 (4.20%) among the less-frequent exacerbators (OR, 3.25; 95% CI, 1.01-11.07; P =
      .0253). In recurrent exacerbators, the frequency of infective exacerbation was
      significantly higher in patients with MBL-deficient genotypes than in those with
      non-MBL-deficient genotypes (4.75 +/- 1.22 vs 3.52 +/- 0.78, respectively; P <
      .0001). In addition, mortality was significantly increased in recurrent
      exacerbators with MBL-deficient genotypes compared with those with non-MBL
      deficient genotypes (66.7% vs 31.0%, respectively; P = .0153). CONCLUSIONS: MBL
      deficiency due to MBL2 polymorphisms increases the risk of recurrent infective
      exacerbation and worsens its outcome in patients with COPD.

PMID- 20688923
TI  - A higher significance of anaerobes: the clone library analysis of bacterial
      pleurisy.
AB  - BACKGROUND: The frequencies of etiologic bacterial agents of intrapleural
      infections reported until now have been widely varied, largely depending on the
      implemented detective methods. The aims of this study were to evaluate bacterial
      etiologies of bacterial pleurisy using a cultivation-independent method. METHODS:
      Pleural fluids were collected from 42 febrile patients with hemipleural effusion.
      The bacterial flora was analyzed by a clone library method using amplified
      fragments of the 16S ribosomal RNA gene (rDNA) with universal primers in addition
      to conventional cultivation methods. RESULTS: Forty-two specimens were obtained
      from 26 patients with bacterial pleurisy, seven with mycobacterial pleurisy, and
      nine with other pleural effusions. In the 26 bacterial cases, 16 (61.5%) showed
      positive results for 16S rDNA sequencing analysis, of which 11 (42.3%) were also
      positive for cultivation method. In seven (43.8%) of the 16 polymerase chain
      reaction-positive cases, anaerobic phylotypes were predominantly detected.
      Anaerobic phylotypes (six of these seven cases) were not detected by cultivation
      method. In nine (34.6%) of the 26 bacterial pleural cases, the results from the
      clone library methods were not accordant with those of the cultivation method. In
      seven of these nine cases, the discrepancies between the two detection methods
      were due to the existence of anaerobes. CONCLUSION: The clone library analysis
      using the 16S rDNA of pleural fluid showed a higher incidence of anaerobic
      bacteria in infectious pleurisy than that previously expected and provided
      additional bacterial information for cultivation methods.

PMID- 20688924
TI  - Depression and functional status are strongly associated with dyspnea in
      interstitial lung disease.
AB  - BACKGROUND: Little is understood about the characteristics of dyspnea in patients
      with interstitial lung disease (ILD), and its severity is likely influenced by
      multiple factors. Depression and functional status are known to influence dyspnea
      in patients with COPD. The aim of this study was to determine the relationship of
      dyspnea with clinical parameters, including depression and functional status, in
      patients with ILD. METHODS: Dyspnea was measured with the Baseline Dyspnea Index
      and the University of California San Diego Shortness of Breath Questionnaire.
      Clinical parameters were recorded. Regression analysis was performed to determine
      independent correlates of dyspnea. RESULTS: Fifty-two subjects were enrolled. The
      two dyspnea scales were strongly correlated (r=-0.79; P<.00005). The mean levels
      of dyspnea were 6.5 and 41.0, representing a moderate degree of dyspnea.
      Clinically meaningful depressive symptoms were found in 23% of subjects.
      Independent correlates of dyspnea severity for each dyspnea scale were depression
      score (P=.002 and P<.0005), 4-m walk time (P=.001 and P=.06), FVC (P=.07 and
      P=.004), and diffusing capacity of the lung for carbon monoxide (P=.007). BMI had
      borderline significant association with the Baseline Dyspnea Index (P=.10).
      CONCLUSIONS: In patients with ILD, dyspnea is associated with depression score,
      functional status, and pulmonary function. These results suggest that attention
      to depression and functional status is important in these patients and that
      treatment directed at these comorbidities may improve dyspnea and quality of
      life. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00611182 ; URL: www.
      clinicaltrials.gov.

PMID- 20688925
TI  - Prehospitalization antiplatelet therapy is associated with a reduced incidence of
      acute lung injury: a population-based cohort study.
AB  - BACKGROUND: Acute lung injury (ALI) is a potentially fatal lung disease with few
      treatment options. Platelet activation is a key component of ALI pathophysiology
      and may provide an opportunity for prevention strategies. We examined the
      association of prehospitalization antiplatelet therapy with development of ALI in
      critically ill patients. METHODS: All Olmsted County, Minnesota, residents with a
      medical ICU admission in the year 2006 were evaluated. Patients with at least one
      major risk factor for ALI who did not meet criteria for ALI at the time of
      hospital admission were included in the analysis. Baseline characteristics, major
      risk factors for ALI, the presence of antiplatelet therapy at the time of
      hospitalization, and the propensity to receive this therapy were determined. The
      primary outcome was ALI or ARDS during the hospitalization. Secondary outcomes
      were ICU and hospital-free days and ICU and hospital mortality. RESULTS: A total
      of 161 patients were evaluated. Seventy-nine (49%) were receiving antiplatelet
      therapy at hospital admission; 33 (21%) developed ALI/ARDS. Antiplatelet therapy
      was associated with a reduced incidence of ALI/ARDS (12.7% vs 28.0%; OR, 0.37;
      95% CI, 0.16-0.84; P = .02). This association remained significant after
      adjusting for confounding variables. CONCLUSIONS: Prehospitalization antiplatelet
      therapy was associated with a reduced incidence of ALI/ARDS. If confirmed in a
      more diverse patient population, these results would support the use of
      antiplatelet agents in an ALI prevention trial.

PMID- 20688926
TI  - Ventilatory inefficiency reflects right ventricular dysfunction in systolic heart
      failure.
AB  - BACKGROUND: An increased minute ventilation (VE)/carbon dioxide production (VCO2)
      relationship, an expression of ventilatory inefficiency (VI), is associated with
      increased morbidity and mortality in patients with left ventricular systolic
      dysfunction (LVSD). A direct link between VI and a specific cardiac abnormality
      has not been established. METHODS: We analyzed cardiopulmonary exercise test
      (CPET) data from patients (N=83) with severe LVSD (ischemic and nonischemic; left
      ventricular ejection fraction [LVEF] 19%+/-7%) and at least moderate exercise
      intolerance. Subjects were stratified into two groups based on the (VE/VCO2 ratio
      at anaerobic threshold (VE/VCO2@AT) (group 1 VE/VCO2@AT<=34; group 2
      VE/VCO2@AT>34). Clinical, CPET, echocardiographic, and hemodynamic data were
      compared between groups. RESULTS: Group 2 subjects had lower exercise capacity
      (peak (VO2, 45.7%+/-11.8% vs 50.4+/-8.9% predicted; P<.05), with a significantly
      lower oxygen pulse (71.6%+/-24.5% vs 85.4+/-18.5% predicted) and maximum systolic
      BP (122+/-19 mm Hg vs 138+/-22 mm Hg; P<.001 for both), suggesting a more blunted
      stroke volume to exercise vs group 1. There were no differences in left
      ventricular (LV) size, LVEF, or mitral regurgitation between the two groups. In
      sharp contrast, group 2 had larger right ventricular (RV) dimensions (4.5+/-1.1
      cm vs 3.9+/-0.8 cm) and more severe RV systolic dysfunction (RV fractional area
      change 26%+/-11% vs 33%+/-12%; tricuspid annular plane systolic excursion [TAPSE]
      1.6+/-0.5 cm vs 2.0+/-0.5 cm; all P<.001) vs group 1. Multivariable analysis
      revealed that only TAPSE and Doppler-estimated pulmonary artery systolic pressure
      were independently associated with VE/VCO2@AT and the (VE/VCO2slope. The
      VE/VCO2@AT, VE/VCO2 slope, and TAPSE had nearly identical predictive value for
      death or transplant. CONCLUSIONS: The present study suggests that VI is a
      functional, noninvasive marker of more advanced right-sided heart dysfunction in
      patients with severe LVSD.

PMID- 20688927
TI  - Vitamin D deficiency and reduced lung function in connective tissue-associated
      interstitial lung diseases.
AB  - BACKGROUND: Vitamin D is a steroid hormone with pleiotropic effects including
      immune system modulation, lung tissue remodeling, and bone health. Vitamin D
      deficiency has been implicated in the development of autoimmune diseases. We
      sought to evaluate the prevalence of vitamin D deficiency in a cohort of patients
      with interstitial lung disease (ILD) and hypothesized that vitamin D deficiency
      would be associated with an underlying connective tissue disease (CTD) and
      reduced lung function. METHODS: Patients in the University of Cincinnati ILD
      Center database were evaluated for serum 25-hydroxyvitamin D levels as part of a
      standardized protocol. Regression analysis evaluated associations between 25
      hydroxyvitamin D levels and other variables. RESULTS: One hundred eighteen
      subjects were included (67 with CTD-ILD, 51 with other forms of ILD). The overall
      prevalence of vitamin D deficiency and insufficiency in the study population was
      38% and 59%, respectively. Those with CTD-ILD were more likely to have vitamin D
      deficiency (52% vs 20%, P < .0001) and insufficiency (79% vs 31%, P < .0001) than
      other forms of ILD. Diminished FVC was associated with lower 25-hydroxyvitamin
      D(3) levels (P = .01). The association between vitamin D insufficiency and CTD
      ILD persisted (OR, 11.8; P < .0001) after adjustment for potential confounders.
      Among subjects with CTD-ILD, reduced 25-hydroxyvitamin D(3) levels were strongly
      associated with reduced lung function (FVC, P = .015; diffusing capacity for
      carbon monoxide, P = .004). CONCLUSIONS: There is a high prevalence of vitamin D
      deficiency in patients with ILD, particularly those with CTD-ILD, and it is
      associated with reduced lung function. Vitamin D may have a role in the
      pathogenesis of CTD-ILD.

PMID- 20688928
TI  - Impact of obesity in patients infected with 2009 influenza A(H1N1).
AB  - OBJECTIVE: A large proportion of patients infected with 2009 influenza A(H1N1)
      (A[H1N1]) are obese. Obesity has been proposed as a risk factor influencing
      outcome in these patients. However, its role remains unclear. We evaluate the
      outcome of patients who are obese and infected with A(H1N1) in the ICU,
      determining whether obesity is a risk factor for mortality. METHODS: This was a
      prospective, observational, and multicenter study performed in 144 ICUs in Spain.
      Data were obtained from the Grupo de Trabajo en Enfermedades Infecciosas de la
      Sociedad Espanola de Medicina Intensiva, Critica y Unidades Coronarias
      (GTEI/SEMICYUC) registry. Adult patients with A(H1N1) that was confirmed by real
      time polymerase chain reaction were included in the analysis. Patients who were
      obese (BMI > 30) were compared with patients who were nonobese. Cox regression
      analysis was used to determine adjusted mortality. Differences of P < .05 were
      considered significant. RESULTS: In January 2010, the GTEI/SEMICYUC registry had
      complete records for 416 patients. One hundred and fifty patients (36.1%) were
      obese, of whom 67 (44.7%) were morbidly obese (BMI > 40). Mechanical ventilation
      (MV) was more frequently applied in patients who were obese (64% vs 52.4%, P <
      .01) Patients with obesity remained on MV longer than patients who were nonobese
      (6.5 +/- 10.3 days vs 9.3 +/- 9.7 days, P = .02), had longer ICU length of stay
      (10.8 +/- 12.1 days vs 13.7 +/- 11.7 days, P = .03), and had longer
      hospitalization (18.2 +/- 14.6 days vs 22.2 +/- 16.5 days, P = .02). Mortality
      adjusted by severity and potential confounders identified that obesity was not
      significantly associated with ICU mortality (hazard ratio, 1.1; 95% CI, 0.69
      1.75; P = .68). CONCLUSIONS: In our cohort, patients who were obese and infected
      with A(H1N1) did not have increased mortality. However, there was an association
      between obesity and higher ICU resource consumption.

PMID- 20688929
TI  - Efficacy and safety of subcutaneous omalizumab vs placebo as add-on therapy to
      corticosteroids for children and adults with asthma: a systematic review.
AB  - BACKGROUND: Omalizumab is a humanized monoclonal anti-IgE for the treatment of
      severe allergic asthma. Because omalizumab targets an immune system molecule,
      there has been particular interest in the drug's safety. METHODS: To establish
      the efficacy and safety of subcutaneous omalizumab as add-on therapy to
      corticosteroids, a systematic review of placebo-controlled studies was performed.
      Primary outcomes were reduction of steroid use and asthma exacerbations.
      Secondary outcome measures included lung function, rescue medication use, asthma
      symptoms, health-related quality of life, and adverse effects. RESULTS: Eight
      trials (3,429 participants) fulfilled the selection criteria. At the end of the
      steroid-reduction phase, patients taking omalizumab were more likely to be able
      to withdraw from corticosteroids completely compared with those taking placebo
      (relative risk [RR] = 1.80; 95% CI, 1.42-2.28; P = .00001). Omalizumab patients
      showed a decreased risk of asthma exacerbations at the end of the stable (RR =
      0.57; 95% CI, 0.48-0.66; P = .0001) and adjustable-steroid phases (RR = 0.55; 95%
      CI, 0.47-0.64; P = .0001); post-hoc analysis suggests this effect was independent
      of duration of treatment, age, severity of asthma, and risk of bias. The
      frequency of serious adverse effects was similar in the omalizumab (3.8%) and
      placebo (5.3%) groups. However, injection site reactions were more frequent in
      the omalizumab patients (19.9% vs 13.2%). There were no indications of increased
      risk of hypersensitivity reactions, cardiovascular effects, or malignant
      neoplasms. CONCLUSIONS: Data indicate that the efficacy of add-on omalizumab in
      patients with moderate-to-severe allergic asthma is accompanied by an acceptable
      safety profile.

PMID- 20688930
TI  - The NLRP3 inflammasome promotes renal inflammation and contributes to CKD.
AB  - Inflammation significantly contributes to the progression of chronic kidney
      disease (CKD). Inflammasome-dependent cytokines, such as IL-1beta and IL-18, play
      a role in CKD, but their regulation during renal injury is unknown. Here, we
      analyzed the processing of caspase-1, IL-1beta, and IL-18 after unilateral
      ureteral obstruction (UUO) in mice, which suggested activation of the Nlrp3
      inflammasome during renal injury. Compared with wild-type mice, Nlrp3(-/-) mice
      had less tubular injury, inflammation, and fibrosis after UUO, associated with a
      reduction in caspase-1 activation and maturation of IL-1beta and IL-18; these
      data confirm that the Nlrp3 inflammasome upregulates these cytokines in the
      kidney during injury. Bone marrow chimeras revealed that Nlrp3 mediates the
      injurious/inflammatory processes in both hematopoietic and nonhematopoietic
      cellular compartments. In tissue from human renal biopsies, a wide variety of
      nondiabetic kidney diseases exhibited increased expression of NLRP3 mRNA, which
      correlated with renal function. Taken together, these results strongly support a
      role for NLRP3 in renal injury and identify the inflammasome as a possible
      therapeutic target in the treatment of patients with progressive CKD.

PMID- 20688931
TI  - Glomerular structure and function require paracrine, not autocrine, VEGF-VEGFR-2
      signaling.
AB  - VEGF is a potent vascular growth factor produced by podocytes in the developing
      and mature glomerulus. Specific deletion of VEGF from podocytes causes glomerular
      abnormalities including profound endothelial cell injury, suggesting that
      paracrine signaling is critical for maintaining the glomerular filtration barrier
      (GFB). However, it is not clear whether normal GFB function also requires
      autocrine VEGF signaling in podocytes. In this study, we sought to determine
      whether an autocrine VEGF-VEGFR-2 loop in podocytes contributes to the
      maintenance of the GFB in vivo. We found that induced, whole-body deletion of
      VEGFR-2 caused marked abnormalities in the kidney and also other tissues,
      including the heart and liver. By contrast, podocyte-specific deletion of the
      VEGFR-2 receptor had no effect on glomerular development or function even up to 6
      months old. Unlike cell culture models, enhanced expression of VEGF by podocytes
      in vivo caused foot process fusion and alterations in slit diaphragm-associated
      proteins; however, inhibition of VEGFR-2 could not rescue this defect. Although
      VEGFR-2 was dispensable in the podocyte, glomerular endothelial cells depended on
      VEGFR-2 expression: postnatal deletion of the receptor resulted in global defects
      in the glomerular microvasculature. Taken together, our results provide strong
      evidence for dominant actions of a paracrine VEGF-VEGFR-2 signaling loop both in
      the developing and in the filtering glomerulus. VEGF produced by the podocyte
      regulates the structure and function of the adjacent endothelial cell.

PMID- 20688932
TI  - Overexpression of VEGF165b in podocytes reduces glomerular permeability.
AB  - The observation that therapeutic agents targeting vascular endothelial growth
      factor-A (VEGF-A) associate with renal toxicity suggests that VEGF plays a role
      in the maintenance of the glomerular filtration barrier. Alternative mRNA
      splicing produces the VEGF(xxx)b family, which consists of antiangiogenic
      peptides that reduce permeability and inhibit tumor growth; the contribution of
      these peptides to normal glomerular function is unknown. Here, we established and
      characterized heterozygous and homozygous transgenic mice that overexpress
      VEGF(165)b specifically in podocytes. We confirmed excess production of
      glomerular VEGF(165)b by reverse transcriptase-PCR, immunohistochemistry, and
      ELISA in both heterozygous and homozygous animals. Macroscopically, the mice
      seemed normal up to 18 months of age, unlike the phenotype of transgenic podocyte
      specific VEGF(164)-overexpressing mice. Animals overexpressing VEGF(165)b,
      however, had a significantly reduced normalized glomerular ultrafiltration
      fraction with accompanying changes in ultrastructure of the glomerular filtration
      barrier on the vascular side of the glomerular basement membrane. These data
      highlight the contrasting properties of VEGF splice variants and their impact on
      glomerular function and phenotype.

PMID- 20688933
TI  - Geographic concentration of poverty and arteriovenous fistula use among ESRD
      patients.
AB  - There is substantial geographic variability in both incident and prevalent
      arteriovenous fistula (AVF) use among patients with ESRD. This study examined the
      degree to which these variations associate with poverty in the county of a
      patient's treatment center. We performed a cross-sectional study including 28,135
      patients treated by 1127 hemodialysis centers in five ESRD networks (16 states)
      between June 1, 2005 and May 31, 2006. We used the 2000 U.S. Census to categorize
      county-level poverty and ascertained incident AVF use from the Medicare CMS 2728
      form. We calculated the 30-month slope of change in AVF prevalence from monthly
      facility reports collected between 2003 and 2005. More than 33% of treatment
      centers were located in high-poverty counties. County poverty inversely
      associated with incident AVF use (P for trend = 0.001). In contrast, substantial
      increases in prevalent AVF rates from 30.9 to 38.6% (P < 0.001) among treatment
      centers did not associate with county poverty (P = 0.9519). In conclusion, the
      concentration of poverty in the county where a treatment is located associates
      with incident AVF use by patients with ESRD but not with subsequent improvement
      in AVF use among prevalent patients. These results suggest that the Medicare ESRD
      program may mitigate poverty effects on AVF use.

PMID- 20688935
TI  - Post-election blues?

PMID- 20688934
TI  - The apolipoprotein L1 (APOL1) gene and nondiabetic nephropathy in African
      Americans.
AB  - Mapping by admixture linkage disequilibrium (LD) detected strong association
      between nonmuscle myosin heavy chain 9 gene (MYH9) variants on chromosome 22 and
      nondiabetic nephropathy in African Americans. MYH9-related variants were posited
      to be the probable, but not necessarily the definitive, causal variants as a
      result of impressive statistical evidence of association, renal expression, and a
      role in autosomal dominant MYH9 disorders characterized by progressive
      glomerulosclerosis (Epstein and Fechtner syndromes). Dense mapping within MYH9
      revealed striking LD patterns and racial variation in risk allele frequencies,
      suggesting population genetic factors such as selection may be operative in this
      region. Genovese and colleagues examined large chromosomal regions adjacent to
      MYH9 using genome-wide association methods and non-HapMap single nucleotide
      polymorphisms identified in Yoruba from the 1000 Genomes project. Statistically
      stronger associations were detected between two independent sequence variants in
      the Apolipoprotein L1 gene (APOL1) and nondiabetic nephropathy in African
      Americans, with odds ratios of 10.5 in idiopathic FSGS and 7.3 in hypertension
      attributed ESRD. These kidney disease risk variants likely rose to high frequency
      in Africa because they confer resistance to trypanosomal infection and protect
      from African sleeping sickness. Risk variants in MYH9 and APOL1 are in strong LD,
      and the genetic risk that was previously attributed to MYH9 may reside, in part
      or in whole, in APOL1, although more complex models of risk cannot be excluded.
      This association likely explains racial disparities in nondiabetic nephropathy as
      a result of the high prevalence of risk alleles in individuals of African
      ancestry.

PMID- 20688936
TI  - Evaluation of a paediatric procedural sedation training and credentialing
      programme: sustainability of change.
AB  - INTRODUCTION: An ongoing comprehensive paediatric procedural sedation (PPS)
      training and credentialing programme to improve patient safety was introduced
      into emergency departments (EDs) at a tertiary children's hospital (Royal
      Children's Hospital; RCH) and a suburban mixed ED (Sunshine Hospital; SH) in
      Melbourne, Australia. The study aimed to establish whether changes in practice
      had been sustained 3 years after implementation of the PPS programme. METHOD: 100
      PPS episodes were identified at both hospitals (50 at each hospital) pre
      implementation, 6 months and 3 years after implementation. This study
      retrospectively analysed 11 proxy markers of sedation safety by review of
      prospectively collected sedation records and medical records. Performance during
      the three time periods was compared using chi(2) testing. RESULTS: Average age
      was 6 years and sedations were mainly for fracture reduction and laceration
      repair. Nitrous oxide and ketamine were the most commonly used agents. Midazolam
      use decreased over the study period. Six months after implementation at both
      hospitals relevant proxy markers of sedation safety were significantly improved
      over the pre-implementation level. Three years after implementation markers of
      sedation safety were still improved over pre-implementation levels. However,
      based on a minimum compliance with seven of 11 sedation safety markers both sites
      deteriorated; RCH from 96% to 80% (p=0.028) and SH from 68% to 32% (p=0.001).
      CONCLUSION: Based on an analysis of proxy markers of sedation safety significant
      changes over pre-implementation sedation care were maintained 3 years after
      implementation of a PPS programme. Documentation of sedation safety markers
      decreased over the study period, more so at the community hospital. To maintain
      educational gains and system change in sedation safety requires ongoing
      resources.

PMID- 20688937
TI  - Local anaesthetic toxicity: are we prepared for the consequences in the Emergency
      Department?
AB  - BACKGROUND: Local anaesthetic agents are commonly encountered in the Emergency
      Department (ED). Local anaesthetic toxicity leading to cardiorespiratory arrest
      is a rare, but potentially fatal, complication of an overdose of these agents. A
      recent innovation in the treatment of severe local anaesthetic toxicity has been
      the introduction of intravenous lipid emulsion therapy (Intralipid 20%). The aim
      of this study was to gauge the current level of knowledge surrounding the
      administration and complications associated with commonly used local anaesthetic
      agents. METHODS: Questionnaires were distributed amongst the training grade
      doctors working in four Emergency Departments. Results were divided into two
      groups for ease of analysis. Core Trainees (CT) and Foundation Year 2 (F2)
      doctors were placed in one group. Specialist Registrars (SPR), Speciality
      Registrars (StR) and Staff Grades (SG) form the other group. RESULTS: The results
      showed that less than half of the CT/F2 group knew the maximum dose of lignocaine
      1%. 80% of these doctors were unable to calculate the maximum dose of lignocaine
      1% for an 80 kg man, and nearly one-third would administer a toxic dose. In
      addition, only one out of 30 in the CT/F2 group were aware of lipid emulsion
      therapy. CONCLUSIONS: Those using local anaesthetic should also be able to
      recognise the signs and symptoms of toxicity should this occur and act
      accordingly. The lack of knowledge amongst the more junior staff, as demonstrated
      by this project, highlights failings in teaching the basics of safe practices in
      the ED.

PMID- 20688938
TI  - Useful clue in Kawasaki disease.

PMID- 20688939
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. BET 1: Use of bedside echocardiography for the diagnosis of pulmonary
      embolism in the emergency department.

PMID- 20688941
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. BET 2: Petechia in the well child.

PMID- 20688943
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. BET 4: Are fascia iliaca blocks an effective method of pain management
      in children with fractured femurs?

PMID- 20688942
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. BET 3: Intensive insulin versus conventional treatment for
      hyperglycaemia in critically ill patients.

PMID- 20688944
TI  - Concurrent ruptured abdominal aortic aneurysm and renal calculus: a case study.

PMID- 20688946
TI  - Phase I safety, pharmacokinetic, and biomarker study of BIBF 1120, an oral triple
      tyrosine kinase inhibitor in patients with advanced solid tumors.
AB  - BIBF 1120 is an oral multitargeted tyrosine kinase inhibitor that blocks the
      activity of vascular endothelial growth factor (VEGF) and other growth factor
      receptors. We have done a phase I study to evaluate the safety, pharmacokinetics,
      and pharmacodynamic biomarkers of BIBF 1120. Patients with advanced refractory
      solid tumors were treated with BIBF 1120 at oral doses of 150 to 250 mg twice
      daily. Drug safety and pharmacokinetics were evaluated, as were baseline and post
      treatment levels of circulating CD117-positive bone marrow-derived progenitor
      cells and plasma soluble VEGF receptor 2 as potential biomarkers for BIBF 1120.
      Twenty-one patients were treated at BIBF 1120 doses of 150 (n = 3), 200 (n = 12),
      or 250 mg twice daily (n = 6). Dose-limiting toxicities of reversible grade 3 or
      4 elevations of liver enzymes occurred in 3 of 12 patients at 200 mg twice daily
      and 3 of 6 patients at 250 mg twice daily. Stable disease was achieved in 16
      (76.2%) patients, and median progression-free survival was 113 days (95%
      confidence interval, 77-119 d). Pharmacokinetic analysis indicated that the
      maximum plasma concentration and area under the curve for BIBF 1120 increased
      with the dose within the dose range tested. Levels of CD117-positive bone marrow
      derived progenitors and soluble VEGF receptor 2 decreased significantly during
      treatment over all BIBF 1120 dose cohorts. In conclusion, the maximum tolerated
      dose of BIBF 1120 in the current study was determined to be 200 mg twice daily,
      and our biomarker analysis indicated that this angiokinase inhibitor is
      biologically active.

PMID- 20688947
TI  - Successful treatment of pan-resistant Klebsiella pneumoniae pneumonia and
      bacteraemia with a combination of high-dose tigecycline and colistin.
AB  - The spread of antimicrobial resistance among members of the Enterobacteriaceae is
      a significant clinical threat. We report the treatment of pan-resistant
      Klebsiella pneumoniae bacteraemia with combination tigecycline and colistin in a
      49-year-old male and review available therapeutic options. Despite a poor
      prognosis, the patient recovered, but remains colonized with the pan-resistant
      isolate.

PMID- 20688948
TI  - Application of a multiplex PCR to cervical cells collected by a paper smear for
      the simultaneous detection of all mucosal human papillomaviruses (HPVs) and
      typing of high-risk HPV types 16 and 18.
AB  - A simple paper smear (PS) method for dry collection and storage of cervical
      specimens was employed to develop an easy multiplex (MPX) PCR for simultaneous
      detection of generic human papillomaviruses (HPVs) as well as typing of the high
      risk HPV-16 and -18, the two clinically most important HPV genotypes, which are
      responsible for more than 80 % of cervical cancers. Multiplexing was performed
      with a small amount of DNA eluted by boiling from a single PS punch in a single
      tube and using a mixture of four pairs of primers specific for the HPV L1
      consensus sequence, HPV-16, HPV-18 and the beta-globin gene. Sixty HPV-positive
      biopsies and corresponding PS specimens from cervical cancer patients as well as
      cervical smears from 100 healthy women with or without abnormal cytology were
      collected both as PSs and in PBS. Detection of HPV DNA from cervical biopsies
      collected in PBS and corresponding cervical scrapes on a PS or in PBS by
      conventional and MPX-PCR showed a concordance of 100 % and adequacy of 93 %. A
      similar comparative study in cervical scrapes from normal women also revealed 100
      % concordance. The technique was validated in a multicentric study at four
      different national laboratories. PSs collected by different centres showed
      variable adequacy (73-82 %) but the use of multiple PS discs for DNA extraction
      significantly increased the adequacy. Integration of PSs with MPX-PCR for the
      detection and typing of HPVs is a highly convenient, efficient, simple and cost
      effective method for large-scale clinico-epidemiological studies and is also
      suitable for HPV vaccine monitoring programmes in resource-poor settings.

PMID- 20688949
TI  - Evaluation of PCR-RFLP analysis targeting hsp65 and rpoB genes for the typing of
      mycobacterial isolates in Malaysia.
AB  - In this study, PCR-RFLP analysis (PRA) targeting hsp65 and rpoB gene regions was
      evaluated for the identification of mycobacterial species isolated from Malaysian
      patients. Overall, the hsp65 PRA identified 92.2 % of 90 isolates compared to
      85.6 % by the rpoB PRA. With 47 rapidly growing species, the hsp65 PRA identified
      fewer (89.4 %) species than the rpoB PRA (95.7 %), but with 23 slow-growing
      species the reverse was true (91.3 % identification by the hsp65 PRA but only
      52.5 % by the rpoB PRA). There were 16 isolates with discordant PRA results,
      which were resolved by 16S rRNA and hsp65 gene sequence analysis. The findings in
      this study suggest that the hsp65 PRA is more useful than the rpoB PRA for the
      identification of Mycobacterium species, particularly with the slow-growing
      members of the genus. In addition, this study reports 5 and 12 novel restriction
      patterns for inclusion in the hsp65 and rpoB PRA algorithms, respectively.

PMID- 20688950
TI  - Human bovine tuberculosis - remains in the differential.
AB  - Mycobacterium bovis is a pathogen of cattle. The unpasteurized milk of affected
      cattle is a source of infection in humans. Despite the screening of cattle and
      the pasteurization of milk, M bovis has not been eradicated. A high index of
      clinical suspicion is needed in symptomatic patients with a history of possible
      exposure. At risk groups include animal workers, farmers, meat packers, vets and
      zoo keepers. Humans are usually infected by the aerosol route. We present two
      cases of human bovine tuberculosis. One was a presumptive case and the second was
      a confirmed case. Both responded well to antituberculous therapy. In the
      confirmed case, there was evidence of transmission to the partner living in the
      same house. Rifampicin prophylaxis was given to the exposed case. The M. bovis
      from the confirmed case was isoniazid resistant, in addition to having the well
      known resistance to pyrazinamide. Isoniazid resistance has been described before
      in those who are immunocompromised. We describe it in an immunocompetent patient.

PMID- 20688951
TI  - Relationship between oral status and prevalence of periodontopathic bacteria on
      the tongues of elderly individuals.
AB  - Colonization of periodontopathic bacteria is associated with increased risk of
      systemic diseases. However, few studies have investigated the relationships
      between oral status factors and health-related quality of life (HR-QOL) and the
      prevalence of such bacteria in elderly individuals. This study investigated the
      prevalence of Porphyromonas gingivalis, Prevotella intermedia, Treponema
      denticola and Tannerella forsythia in 165 community-dwelling functionally
      independent 85-year-old Japanese individuals (93 dentate, 72 edentulous) and the
      relationship to oral status, including oral malodour and HR-QOL. All four of the
      studied periodontopathic bacteria were found more frequently in tongue coating
      samples from dentate than edentulous subjects, and the prevalence of
      Porphyromonas gingivalis, Prevotella intermedia and Treponema denticola was
      significantly related to the number of teeth with a periodontal pocket depth >=4
      mm. These results suggest the existence of a stable circulation of
      periodontopathic bacteria between the gingival sulcus and tongue coating over
      time with teeth. In addition, the presence of teeth with a deep pocket and
      colonization of Treponema denticola were positively related to the level of
      CH(3)SH, whilst the number of present teeth contributed positively to HR-QOL,
      especially with regard to mental health. In conclusion, as the dentate state can
      retain colonization of periodontopathic pathogens in the oral cavity, both
      periodontal treatment and tongue care are important for maintaining a healthy
      oral status in the elderly, and possibly result in avoidance of risk for tooth
      loss and decline in HR-QOL, as well as protecting from systemic diseases.

PMID- 20688952
TI  - Comparison of endodontic bacterial community structures in root-canal-treated
      teeth with or without apical periodontitis.
AB  - Bacterial occurrence in treated root canals, even in patients without post
      treatment apical periodontitis, raises the possibility that factors other than
      mere bacterial presence can be determinants for a favourable outcome of
      endodontic treatment. Because these factors may be related to the bacterial
      communities colonizing the root canal, including virulence, density and
      interactions, the objective of this study was to compare the community structures
      found in root-canal-treated teeth with (12 samples) and without (11 samples)
      apical periodontitis lesions by means of a PCR-denaturing gradient gel
      electrophoresis fingerprinting approach. Results confirmed a polymicrobial
      composition even in treated patients without post-treatment disease. A large
      microbial community diversity was observed for treated teeth both with or without
      disease, but no specific pattern was detected for diseased teeth. Nevertheless,
      the number of bands from samples with apical periodontitis lesions was
      statistically significantly higher (P=0.04) than that from samples collected from
      root-canal-treated teeth without post-treatment apical periodontitis.
      Furthermore, predominant bands in samples from patients with apical disease were
      also observed.

PMID- 20688954
TI  - Changes in dispositional empathy in American college students over time: a meta
      analysis.
AB  - The current study examines changes over time in a commonly used measure of
      dispositional empathy. A cross-temporal meta-analysis was conducted on 72 samples
      of American college students who completed at least one of the four subscales
      (Empathic Concern, Perspective Taking, Fantasy, and Personal Distress) of the
      Interpersonal Reactivity Index (IRI) between 1979 and 2009 (total N = 13,737).
      Overall, the authors found changes in the most prototypically empathic subscales
      of the IRI: Empathic Concern was most sharply dropping, followed by Perspective
      Taking. The IRI Fantasy and Personal Distress subscales exhibited no changes over
      time. Additional analyses found that the declines in Perspective Taking and
      Empathic Concern are relatively recent phenomena and are most pronounced in
      samples from after 2000.

PMID- 20688953
TI  - Slingshot: a PiggyBac based transposon system for tamoxifen-inducible 'self
      inactivating' insertional mutagenesis.
AB  - We have developed a self-inactivating PiggyBac transposon system for tamoxifen
      inducible insertional mutagenesis from a stably integrated chromosomal donor.
      This system, which we have named 'Slingshot', utilizes a transposon carrying
      elements for both gain- and loss-of-function screens in vitro. We show that the
      Slingshot transposon can be efficiently mobilized from a range of chromosomal
      loci with high inducibility and low background generating insertions that are
      randomly dispersed throughout the genome. Furthermore, we show that once the
      Slingshot transposon has been mobilized it is not remobilized producing stable
      clonal integrants in all daughter cells. To illustrate the efficacy of Slingshot
      as a screening tool we set out to identify mediators of resistance to puromycin
      and the chemotherapeutic drug vincristine by performing genetrap screens in mouse
      embryonic stem cells. From these genome-wide screens we identified multiple
      independent insertions in the multidrug resistance transporter genes Abcb1a/b and
      Abcg2 conferring resistance to drug treatment. Importantly, we also show that the
      Slingshot transposon system is functional in other mammalian cell lines such as
      human HEK293, OVCAR-3 and PE01 cells suggesting that it may be used in a range of
      cell culture systems. Slingshot represents a flexible and potent system for
      genome-wide transposon-mediated mutagenesis with many potential applications.

PMID- 20688955
TI  - Fetal globin expression is regulated by Friend of Prmt1.
AB  - An estimated 6% to 7% of the earth's population carries a mutation affecting red
      blood cell function. The beta-thalassemias and sickle cell disease are the most
      common monogenic disorders caused by these mutations. Increased levels of gamma
      globin ameliorate the severity of these diseases because fetal hemoglobin (HbF;
      alpha2gamma2) can effectively replace adult hemoglobin (HbA; alpha2beta2) and
      counteract polymerization of sickle hemoglobin (HbS; alpha2beta(S)2). Therefore,
      understanding the molecular mechanism of globin switching is of biologic and
      clinical importance. Here, we show that the recently identified chromatin factor
      Friend of Prmt1 (FOP) is a critical modulator of gamma-globin gene expression.
      Knockdown of FOP in adult erythroid progenitors strongly induces HbF.
      Importantly, gamma-globin expression can be elevated in cells from beta
      thalassemic patients by reducing FOP levels. These observations identify FOP as a
      novel therapeutic target in beta-hemoglobinopathies.

PMID- 20688956
TI  - Genetic manipulation of AML1-ETO-induced expansion of hematopoietic precursors in
      a Drosophila model.
AB  - Among mutations in human Runx1/AML1 transcription factors, the t(8;21)(q22;q22)
      genomic translocation that creates an AML1-ETO fusion protein is implicated in
      etiology of the acute myeloid leukemia. To identify genes and components
      associated with this oncogene we used Drosophila as a genetic model. Expression
      of AML1-ETO caused an expansion of hematopoietic precursors in Drosophila, which
      expressed high levels of reactive oxygen species (ROS). Mutations in functional
      domains of the fusion protein suppress the proliferative phenotype. In a genetic
      screen, we found that inactivation of EcRB1 or activation of Foxo and superoxide
      dismutase-2 (SOD2) suppress the AML1-ETO-induced phenotype by reducing ROS
      expression in the precursor cells. Our studies indicate that ROS is a signaling
      factor promoting maintenance of normal as well as the aberrant myeloid precursors
      and suggests the importance of antioxidant enzymes and their regulators as
      targets for further study in the context of leukemia.

PMID- 20688957
TI  - Improved regulatory T-cell activity in patients with chronic immune
      thrombocytopenia treated with thrombopoietic agents.
AB  - Immune thrombocytopenia (ITP) is an autoantibody-mediated bleeding disorder with
      both accelerated platelet destruction and impaired platelet production. We and
      others have described impaired regulatory CD4(+)CD25(hi) T cells (Treg) numbers
      and/or suppressive function in ITP patients. Clinical trials using thrombopoietic
      agents to stimulate platelet production have shown favorable outcomes in ITP
      patients, but information on the immunologic responses of treated patients are
      lacking. We studied the immunologic profile of chronic ITP patients before (n =
      10) and during treatment with thrombopoietin receptor (TPO-R) agonists (n = 9).
      Treg activity, as measured by suppression of proliferation of autologous CD4(+)
      CD25(-) cells, was improved in patients on treatment (P < .05), and the
      improvement correlated with reduction in interleukin-2-producing CD4(+) cells,
      consistent with dampening of immune responses. There was a concomitant increase
      in total circulating transforming growth factor-beta1 (TGF-beta1) levels (P =
      .002) in patients on treatment, and the levels of TGF-beta1 correlated with the
      degree of improvement in platelet counts (r = .8, P = .0002). This suggests that
      platelets in patients on TPO-R treatment may play a role in improving Treg
      function, either directly or indirectly by enhanced release of TGF-beta1 as a
      result of greater platelet turnover. In conclusion, our findings suggest that
      thrombopoietic agents in patients with ITP have profound effects to restore
      immune tolerance.

PMID- 20688958
TI  - Induction of FPN1 transcription by MTF-1 reveals a role for ferroportin in
      transition metal efflux.
AB  - Ferroportin (Fpn) is the only known iron exporter in vertebrate cells and plays a
      critical role in iron homeostasis regulating cytosolic iron levels and exporting
      iron to plasma. Ferroportin1 (FPN1) expression can be transcriptionally regulated
      by iron as well as other transition metals. Fpn can also be posttranslationally
      regulated by hepcidin-mediated internalization and degradation. We demonstrate
      that zinc and cadmium induce FPN1 transcription through the action of Metal
      Transcription Factor-1 (MTF-1). These transition metals induce MTF-1
      translocation into the nucleus. Zinc leads to MTF-1 binding to the FPN1 promoter,
      while iron does not. Silencing of MTF-1 reduces FPN1 transcription in response to
      zinc but not in response to iron. The mouse FPN1 promoter contains 2 MTF-1
      binding sites and mutation of those sites affects the zinc and cadmium-dependent
      expression of a FPN1 promoter reporter construct. We demonstrate that Fpn can
      transport zinc and can protect zinc sensitive cells from high zinc toxicity.

PMID- 20688959
TI  - How I treat HIV-associated multicentric Castleman disease.
AB  - HIV-associated plasmablastic multicentric Castleman disease is an increasingly
      frequent diagnosis. Kaposi sarcoma herpesvirus is found in the monotypic
      polyclonal plasmablasts that characterize this disease. Unlike Kaposi sarcoma,
      the incidence does not correlate with CD4 cell count or use of highly active
      antiretroviral therapy. It is a relapsing and remitting illness, and diagnostic
      criteria are emerging that define disease activity based on the presence of a
      fever and raised C-reactive protein coupled with a list of clinical features.
      Treatment protocols increasingly stratify therapy according to performance status
      and organ involvement. I advocate rituximab monotherapy for good performance
      status patients without organ involvement and rituximab with chemotherapy for
      more aggressive disease. The success of antiherpesvirus agents in controlling
      active disease is limited, but valganciclovir may have a role as maintenance
      therapy in the future.

PMID- 20688960
TI  - Functional divergence between 2 chemokines is conferred by single amino acid
      change.
AB  - CXCL4 and CXCL4L1 are 2 closely related CXC chemokines that exhibit potent
      antiangiogenic activity. Because interactions with glycosaminoglycans play a
      crucial role in chemokines activity, we determined the binding parameters of
      CXCL4 and CXCL4L1 for heparin, heparan sulfate, and chondroitin sulfate B. We
      further demonstrated that the Leu67/His67 substitution is critical for the
      decrease in glycan binding of CXCL4L1 but also for the increase of its
      angiostatic activities. Using a set of mutants, we show that glycan affinity and
      angiostatic properties are not completely related. These data are reinforced
      using a monoclonal antibody that specifically recognizes structural modifications
      in CXCL4L1 due to the presence of His67 and that blocks its biologic activity. In
      vivo, half-life and diffusibility of CXCL4L1 compared with CXCL4 is strongly
      increased. As opposed to CXCL4L1, CXCL4 is preferentially retained at its site of
      expression. These findings establish that, despite small differences in the
      primary structure, CXCL4L1 is highly distinct from CXCL4. These observations are
      not only of great significance for the antiangiogenic activity of CXCL4L1 and for
      its potential use in clinical development but also for other biologic processes
      such as inflammation, thrombosis or tissue repair.

PMID- 20688961
TI  - Dasatinib, an immunomodulator?

PMID- 20688963
TI  - Rethinking warfarin reversal.

PMID- 20688962
TI  - Union of forces advances myeloma care.

PMID- 20688964
TI  - O tissue factor, where art thou?

PMID- 20688965
TI  - The classification of systemic mastocytosis should include mast cell leukemia
      (MCL) and systemic mastocytosis with a clonal hematologic non-mast cell lineage
      disease (SM-AHNMD).

PMID- 20688966
TI  - Increased susceptibility to iron deficiency of Tmprss6-haploinsufficient mice.

PMID- 20688968
TI  - No evidence for tissue factor on platelets.

PMID- 20688967
TI  - Pulmonary hypertension and NO in sickle cell.

PMID- 20688969
TI  - ClotBase: a knowledgebase on proteins involved in blood coagulation.

PMID- 20688970
TI  - Invited reply to ''The death knoll for the MMSE: has it outlived its purpose?''.

PMID- 20688971
TI  - Evolutionary constraints of phosphorylation in eukaryotes, prokaryotes, and
      mitochondria.
AB  - High accuracy mass spectrometry has proven to be a powerful technology for the
      large scale identification of serine/threonine/tyrosine phosphorylation in the
      living cell. However, despite many described phosphoproteomes, there has been no
      comparative study of the extent of phosphorylation and its evolutionary
      conservation in all domains of life. Here we analyze the results of
      phosphoproteomics studies performed with the same technology in a diverse set of
      organisms. For the most ancient organisms, the prokaryotes, only a few hundred
      proteins have been found to be phosphorylated. Applying the same technology to
      eukaryotic species resulted in the detection of thousands of phosphorylation
      events. Evolutionary analysis shows that prokaryotic phosphoproteins are
      preferentially conserved in all living organisms, whereas-site specific
      phosphorylation is not. Eukaryotic phosphosites are generally more conserved than
      their non-phosphorylated counterparts (with similar structural constraints)
      throughout the eukaryotic domain. Yeast and Caenorhabditis elegans are two
      exceptions, indicating that the majority of phosphorylation events evolved after
      the divergence of higher eukaryotes from yeast and reflecting the unusually large
      number of nematode-specific kinases. Mitochondria present an interesting
      intermediate link between the prokaryotic and eukaryotic domains. Applying the
      same technology to this organelle yielded 174 phosphorylation sites mapped to 74
      proteins. Thus, the mitochondrial phosphoproteome is similarly sparse as the
      prokaryotic phosphoproteomes. As expected from the endosymbiotic theory,
      phosphorylated as well as non-phosphorylated mitochondrial proteins are
      significantly conserved in prokaryotes. However, mitochondrial phosphorylation
      sites are not conserved throughout prokaryotes, consistent with the notion that
      serine/threonine phosphorylation in prokaryotes occurred relatively recently in
      evolution. Thus, the phosphoproteome reflects major events in the evolution of
      life.

PMID- 20688972
TI  - Purpura fulminans: a rare presentation of a common disease.
AB  - Malaria is a common health problem in India and contributes about 80% of the
      total cases in South East Asia. Falciparum malaria is known for its various
      complications, including cerebral malaria, severe anaemia, acute renal failure,
      acute lung injury, jaundice (and hepatic involvement), hypoglycaemia and
      circulatory collapse. We hereby report on a young male who was suffering from
      complicated falciparum malaria, and had purpura fulminans along with laboratory
      features suggestive of disseminated intravascular coagulation. He was treated
      with intravenous (IV) artesunate, low molecular weight heparin followed by
      warfarin in addition to IV fluids to which he showed gradual response. We have
      presented this case to make others vigilant enough to suspect malaria in
      differential diagnosis of purpura fulminans.

PMID- 20688973
TI  - Epileptiform seizures revealing neurocysticercosis: report of two clinical cases
      in Libreville, Gabon.
AB  - Neurocysticercosis (NCC) is the most common helminth infection of the central
      nervous system. It is caused by the larval form of the tapeworm Taenia solium and
      is increasingly recognized as a major cause of neurologic disease worldwide.
      Epilepsy is the usual mode of revelation. Neuroimaging, including computed
      tomography and magnetic resonance imaging, combined with serodiagnostic
      techniques have led to this increased recognition. We report on two cases (one co
      infected with the HIV) of NCC diagnosed in 2006 and 2008 at the Omar Bongo
      Ondimba Army Teaching Hospital. New-onset epilepsy revealed the two cases.
      Medical treatment with albendazole, anti-epileptic drugs and corticosteroids led
      to full recovery. NCC should be considered in tropical countries as a leading
      cause of epilepsy. Moreover, NCC should be included in the differential diagnosis
      of neurologic infections in HIV patients in endemic populations.

PMID- 20688974
TI  - The anticonvulsive drug lamotrigine blocks neuronal {alpha}4{beta}2 nicotinic
      acetylcholine receptors.
AB  - Lamotrigine (LTG), an anticonvulsive drug, is often used for the treatment of a
      variety of epilepsies. In addition to block of sodium channels, LTG may act on
      other targets to exert its antiepileptic effect. In the present study, we
      evaluated the effects of LTG on neuronal nicotinic acetylcholine receptors
      (nAChRs) using the patch-clamp technique on human alpha4beta2-nAChRs
      heterologously expressed in the SH-EP1 cell line and on native alpha4beta2-nAChRs
      in dopaminergic (DA) neurons in rat ventral tegmental area (VTA). In SH-EP1
      cells, LTG diminished the peak and steady-state components of the inward
      alpha4beta2-nAChR-mediated currents. This effect exhibited concentration-,
      voltage- and use-dependent behavior. Nicotine dose-response curves showed that in
      the presence of LTG, the nicotine-induced maximal current was reduced, suggesting
      a noncompetitive inhibition. These findings suggest that LTG inhibits human
      neuronal alpha4beta2-nAChR function through an open-channel blocking mechanism.
      LTG-induced inhibition in alpha4beta2-nAChRs was more profound when preceded by a
      2-min pretreatment, after which the nicotine-induced current was reduced even
      without coapplication of LTG, suggesting that LTG is also able to inhibit
      alpha4beta2-nAChRs without channel activation. In freshly dissociated VTA DA
      neurons, LTG inhibited alpha4beta2-nAChR-mediated currents but did not affect
      glutamate- or GABA-induced currents, indicating that LTG selectively inhibits
      nAChR function. Collectively, our data suggest that the neuronal alpha4beta2
      nAChR is likely an important target for mediating the anticonvulsive effect of
      LTG and the blockade of alpha4beta2-nAChR possibly underlying the mechanism
      through which LTG effectively controls some types of epilepsy, such as autosomal
      dominant nocturnal frontal lobe epilepsy or juvenile myoclonic epilepsy.

PMID- 20688975
TI  - Inhibitory influence of protease-activated receptor 2 and E-prostanoid receptor
      stimulants in lipopolysaccharide models of acute airway inflammation.
AB  - Protease-activated receptors (PARs) are widely expressed throughout the
      respiratory tract, and PAR(2) has been investigated as a potential drug target
      for inflammatory airway diseases. The primary focus of this study was to
      determine the extent to which PAR(2)-activating peptides modulate
      lipopolysaccharide (LPS)-induced airway neutrophilia in mice and establish the
      underlying mechanisms. Intranasal administration of LPS induced dose- and time
      dependent increases in the number of neutrophils recovered from bronchoalveolar
      lavage (BAL) fluid of mice. Coadministration of the PAR(2)-activating peptide f
      LIGRL inhibited LPS-induced neutrophilia at 3 and 6 h after inoculation. PAR(2)
      mediated inhibition of LPS-induced neutrophilia was mimicked by prostaglandin
      E(2) (PGE(2)) and butaprost [selective E-prostanoid (EP(2)) receptor agonist],
      and blocked by parecoxib (cyclooxygenase 2 inhibitor) and 6-isopropoxy-9
      oxoxanthene-2-carboxylic acid (AH6809) (EP(1)/EP(2) receptor antagonist). PAR(2)
      activating peptides also blunted early increases in the levels of the key
      neutrophil chemoattractants keratinocyte-derived chemokine and macrophage
      inflammatory protein 2 (MIP-2) in the BAL of LPS-exposed mice. However, neither
      PAR(2)-activating peptides nor PGE(2) inhibited LPS-induced generation of MIP-2
      in cultures of primary murine alveolar macrophages In summary, PAR(2)-activating
      peptides and PGE(2) suppressed LPS-induced neutrophilia in murine airways,
      independently of an inhibitory action on MIP-2 generation by alveolar
      macrophages.

PMID- 20688976
TI  - A framework for oligonucleotide microarray preprocessing.
AB  - MOTIVATION: The availability of flexible open source software for the analysis of
      gene expression raw level data has greatly facilitated the development of widely
      used preprocessing methods for these technologies. However, the expansion of
      microarray applications has exposed the limitation of existing tools. RESULTS: We
      developed the oligo package to provide a more general solution that supports a
      wide range of applications. The package is based on the BioConductor principles
      of transparency, reproducibility and efficiency of development. It extends the
      existing tools and leverages existing code for visualization, accessing data and
      widely used preprocessing routines. The oligo package implements a unified
      paradigm for preprocessing data and interfaces with other BioConductor tools for
      downstream analysis. Our infrastructure is general and can be used by other
      BioConductor packages. AVAILABILITY: The oligo package is freely available
      through BioConductor, http://www.bioconductor.org.

PMID- 20688977
TI  - The metabolic and developmental roles of carotenoid cleavage dioxygenase4 from
      potato.
AB  - The factors that regulate storage organ carotenoid content remain to be fully
      elucidated, despite the nutritional and economic importance of this class of
      compound. Recent findings suggest that carotenoid pool size is determined, at
      least in part, by the activity of carotenoid cleavage dioxygenases. The aim of
      this study was to investigate whether Carotenoid Cleavage Dioxygenase4 (CCD4)
      activity affects potato (Solanum tuberosum) tuber carotenoid content. Microarray
      analysis revealed elevated expression of the potato CCD4 gene in mature tubers
      from white-fleshed cultivars compared with higher carotenoid yellow-fleshed
      tubers. The expression level of the potato CCD4 gene was down-regulated using an
      RNA interference (RNAi) approach in stable transgenic lines. Down-regulation in
      tubers resulted in an increased carotenoid content, 2- to 5-fold higher than in
      control plants. The increase in carotenoid content was mainly due to elevated
      violaxanthin content, implying that this carotenoid may act as the in vivo
      substrate. Although transcript level was also reduced in plant organs other than
      tubers, such as leaves, stems, and roots , there was no change in carotenoid
      content in these organs. However, carotenoid levels were elevated in flower
      petals from RNAi lines. As well as changes in tuber carotenoid content, tubers
      from RNAi lines exhibited phenotypes such as heat sprouting, formation of chain
      tubers, and an elongated shape. These results suggest that the product of the
      CCD4 reaction may be an important factor in tuber heat responses.

PMID- 20688979
TI  - Characterization of a developmental root response caused by external ammonium
      supply in Lotus japonicus.
AB  - Plants respond to changes of nutrient availability in the soil by modulating
      their root system developmental plan. This response is mediated by systemic
      changes of the nutritional status and/or by local perception of specific signals.
      The effect of nitrate on Arabidopsis (Arabidopsis thaliana) root development
      represents a paradigm of these responses, and nitrate transporters are involved
      both in local and systemic control. Ammonium (NH(4)(+)) represents an important
      nitrogen (N) source for plants, although toxicity symptoms are often associated
      with high NH(4)(+) concentration when this is present as the only N source. The
      reason for these effects is still controversial, and mechanisms associating
      ammonium supply and plant developmental programs are completely unknown. We
      determined in Lotus japonicus the range of ammonium concentration that
      significantly inhibits the elongation of primary and lateral roots without
      affecting the biomass of the shoot. The comparison of the growth phenotypes in
      different N conditions indicated the specificity of the ammonium effect,
      suggesting that this was not mediated by assimilatory negative feedback
      mechanisms. In the range of inhibitory NH(4)(+) conditions, only the LjAMT1;3
      gene, among the members of the LjAMT1 family, showed a strong increased
      transcription that was reflected by an enlarged topology of expression.
      Remarkably, the short-root phenotype was phenocopied in transgenic lines by
      LjAMT1;3 overexpression independently of ammonium supply, and the same phenotype
      was not induced by another AMT1 member. These data describe a new plant mechanism
      to cope with environmental changes, giving preliminary information on putative
      actors involved in this specific ammonium-induced response.

PMID- 20688978
TI  - Light quality-mediated petiole elongation in Arabidopsis during shade avoidance
      involves cell wall modification by xyloglucan endotransglucosylase/hydrolases.
AB  - Some plants can avoid shaded conditions via rapid shoot elongation, thus growing
      into better lit areas in a canopy. Cell wall-modifying mechanisms promoting this
      elongation response, therefore, are important regulatory points during shade
      avoidance. Two major cell wall-modifying protein families are expansins and
      xyloglucan endotransglucosylase/hydrolases (XTHs). The role of these proteins
      during shade avoidance was studied in Arabidopsis (Arabidopsis thaliana). In
      response to two shade cues, low red to far-red light (implying neighbor
      proximity) and green shade (mimicking dense canopy conditions), Arabidopsis
      showed classic shade avoidance features: petiole elongation and leaf hyponasty.
      Measurement of the apoplastic proton flux in green shade-treated petioles
      revealed a rapid efflux of protons into the apoplast within minutes, unlike white
      light controls. This apoplastic acidification probably provides the acidic pH
      required for the optimal activity of cell wall-modifying proteins like expansins
      and XTHs. Acid-induced extension, expansin susceptibility, and extractable
      expansin activity were similar in petioles from white light- and shade-treated
      plants. XTH activity, however, was high in petioles exposed to shade treatments.
      Five XTH genes (XTH9, -15, -16, -17, and -19) were positively regulated by low
      red to far-red light conditions, while the latter four and XTH22 showed a
      significant up-regulation also in response to green shade. Consistently, knockout
      mutants for two of these XTH genes also had reduced or absent shade avoidance
      responses to these light signals. These results point toward the cell wall as a
      vital regulatory point during shade avoidance.

PMID- 20688980
TI  - The chlorine isotope composition of the moon and implications for an anhydrous
      mantle.
AB  - Arguably, the most striking geochemical distinction between Earth and the Moon
      has been the virtual lack of water (hydrogen) in the latter. This conclusion was
      recently challenged on the basis of geochemical data from lunar materials that
      suggest that the Moon's water content might be far higher than previously
      believed. We measured the chlorine isotope composition of Apollo basalts and
      glasses and found that the range of isotopic values [from -1 to +24 per mil (per
      thousand) versus standard mean ocean chloride] is 25 times the range for Earth.
      The huge isotopic spread is explained by volatilization of metal halides during
      basalt eruption--a process that could only occur if the Moon had hydrogen
      concentrations lower than those of Earth by a factor of approximately 10(4) to
      10(5), implying that the lunar interior is essentially anhydrous.

PMID- 20688981
TI  - Aryl hydrocarbon receptor antagonists promote the expansion of human
      hematopoietic stem cells.
AB  - Although practiced clinically for more than 40 years, the use of hematopoietic
      stem cell (HSC) transplants remains limited by the ability to expand these cells
      ex vivo. An unbiased screen with primary human HSCs identified a purine
      derivative, StemRegenin 1 (SR1), that promotes the ex vivo expansion of CD34+
      cells. Culture of HSCs with SR1 led to a 50-fold increase in cells expressing
      CD34 and a 17-fold increase in cells that retain the ability to engraft
      immunodeficient mice. Mechanistic studies show that SR1 acts by antagonizing the
      aryl hydrocarbon receptor (AHR). The identification of SR1 and AHR modulation as
      a means to induce ex vivo HSC expansion should facilitate the clinical use of HSC
      therapy.

PMID- 20688982
TI  - Structural basis for activation of class Ib ribonucleotide reductase.
AB  - The class Ib ribonucleotide reductase of Escherichia coli can initiate reduction
      of nucleotides to deoxynucleotides with either a Mn(III)2-tyrosyl radical (Y*) or
      a Fe(III)2-Y* cofactor in the NrdF subunit. Whereas Fe(III)2-Y* can self-assemble
      from Fe(II)2-NrdF and O2, activation of Mn(II)2-NrdF requires a reduced
      flavoprotein, NrdI, proposed to form the oxidant for cofactor assembly by
      reduction of O2. The crystal structures reported here of E. coli Mn(II)2-NrdF and
      Fe(II)2-NrdF reveal different coordination environments, suggesting distinct
      initial binding sites for the oxidants during cofactor activation. In the
      structures of Mn(II)2-NrdF in complex with reduced and oxidized NrdI, a
      continuous channel connects the NrdI flavin cofactor to the NrdF Mn(II)2 active
      site. Crystallographic detection of a putative peroxide in this channel supports
      the proposed mechanism of Mn(III)2-Y* cofactor assembly.

PMID- 20688983
TI  - Strange metal transport realized by gauge/gravity duality.
AB  - Fermi liquid theory explains the thermodynamic and transport properties of most
      metals. The so-called non-Fermi liquids deviate from these expectations and
      include exotic systems such as the strange metal phase of cuprate superconductors
      and heavy fermion materials near a quantum phase transition. We used the anti-de
      Sitter/conformal field theory correspondence to identify a class of non-Fermi
      liquids; their low-energy behavior is found to be governed by a nontrivial
      infrared fixed point, which exhibits nonanalytic scaling behavior only in the
      time direction. For some representatives of this class, the resistivity has a
      linear temperature dependence, as is the case for strange metals.

PMID- 20688985
TI  - Translational ecology.

PMID- 20688984
TI  - Glutamine deamidation and dysfunction of ubiquitin/NEDD8 induced by a bacterial
      effector family.
AB  - A family of bacterial effectors including Cif homolog from Burkholderia
      pseudomallei (CHBP) and Cif from Enteropathogenic Escherichia coli (EPEC) adopt a
      functionally important papain-like hydrolytic fold. We show here that CHBP was a
      potent inhibitor of the eukaryotic ubiquitination pathway. CHBP acted as a
      deamidase that specifically and efficiently deamidated Gln40 in ubiquitin and
      ubiquitin-like protein NEDD8 both in vitro and during Burkholderia infection.
      Deamidated ubiquitin was impaired in supporting ubiquitin-chain synthesis. Cif
      selectively deamidated NEDD8, which abolished the activity of neddylated Cullin
      RING ubiquitin ligases (CRLs). Ubiquitination and ubiquitin-dependent degradation
      of multiple CRL substrates were impaired by Cif in EPEC-infected cells. Mutations
      of substrate-contacting residues in Cif abolished or attenuated EPEC-induced
      cytopathic phenotypes of cell cycle arrest and actin stress fiber formation.

PMID- 20688986
TI  - Cancer research. As questions grow, Duke halts trials, launches investigation.

PMID- 20688987
TI  - Biosecurity. Defining select agents by DNA sequence.

PMID- 20688989
TI  - Energy. Fresh start for fusion project as new leader shakes up management.

PMID- 20688988
TI  - Physics. Diamond feats give quantum computing a solid boost.

PMID- 20688993
TI  - Climate change. 'Arctic armageddon' needs more science, less hype.

PMID- 20688991
TI  - Infectious disease. New map illustrates risk from the 'other' malaria.

PMID- 20688994
TI  - Marine biology. Seeing deeply into the sea's biodiversity.

PMID- 20688995
TI  - Profile: Douglas and Pamela Soltis. The power of two.

PMID- 20688998
TI  - The time of young scientists.

PMID- 20688999
TI  - Cuban health care: consider the source.

PMID- 20689000
TI  - The silver lining of language loss.

PMID- 20689002
TI  - Cuban health care: benefits without costs.

PMID- 20689003
TI  - Intellectual property. China's innovation landscape.

PMID- 20689004
TI  - Epidemiology. Bats, in black and white.

PMID- 20689005
TI  - Chemistry. The give and take of alcohol activation.

PMID- 20689006
TI  - Developmental biology. Which parental gene gets the upper hand?

PMID- 20689007
TI  - Environmental science. When UV meets fresh water.

PMID- 20689008
TI  - Physics. In praise of exact quantization.

PMID- 20689009
TI  - Developmental biology. Versatile germline genes.

PMID- 20689010
TI  - Vanadium nitrogenase reduces CO.
AB  - Vanadium nitrogenase not only reduces dinitrogen to ammonia but also reduces
      carbon monoxide to ethylene, ethane, and propane. The parallelism between the two
      reactions suggests a potential link in mechanism and evolution between the carbon
      and nitrogen cycles on Earth.

PMID- 20689011
TI  - Role of secondary sensory cortices in emotional memory storage and retrieval in
      rats.
AB  - Visual, acoustic, and olfactory stimuli associated with a highly charged
      emotional situation take on the affective qualities of that situation. Where the
      emotional meaning of a given sensory experience is stored is a matter of debate.
      We found that excitotoxic lesions of auditory, visual, or olfactory secondary
      sensory cortices impaired remote, but not recent, fear memories in rats. Amnesia
      was modality-specific and not due to an interference with sensory or emotional
      processes. In these sites, memory persistence was dependent on ongoing protein
      kinase Mzeta activity and was associated with an increased activity of layers II
      IV, thus suggesting a synaptic strengthening of corticocortical connections.
      Lesions of the same areas left intact the memory of sensory stimuli not
      associated with any emotional charge. We propose that secondary sensory cortices
      support memory storage and retrieval of sensory stimuli that have acquired a
      behavioral salience with the experience.

PMID- 20689012
TI  - Normal modes and density of states of disordered colloidal solids.
AB  - The normal modes and the density of states (DOS) of any material provide a basis
      for understanding its thermal and mechanical transport properties. In perfect
      crystals, normal modes are plane waves, but they can be complex in disordered
      systems. We have experimentally measured normal modes and the DOS in a disordered
      colloidal crystal. The DOS shows Debye-like behavior at low energies and an
      excess of modes, or Boson peak, at higher energies. The normal modes take the
      form of plane waves hybridized with localized short wavelength features in the
      Debye regime but lose both longitudinal and transverse plane-wave character at a
      common energy near the Boson peak.

PMID- 20689013
TI  - Massive Dirac fermion on the surface of a magnetically doped topological
      insulator.
AB  - In addition to a bulk energy gap, topological insulators accommodate a
      conducting, linearly dispersed Dirac surface state. This state is predicted to
      become massive if time reversal symmetry is broken, and to become insulating if
      the Fermi energy is positioned inside both the surface and bulk gaps. We
      introduced magnetic dopants into the three-dimensional topological insulator
      dibismuth triselenide (Bi2Se3) to break the time reversal symmetry and further
      position the Fermi energy inside the gaps by simultaneous magnetic and charge
      doping. The resulting insulating massive Dirac fermion state, which we observed
      by angle-resolved photoemission, paves the way for studying a range of
      topological phenomena relevant to both condensed matter and particle physics.

PMID- 20689014
TI  - Quantum correlations in optical angle-orbital angular momentum variables.
AB  - Entanglement of the properties of two separated particles constitutes a
      fundamental signature of quantum mechanics and is a key resource for quantum
      information science. We demonstrate strong Einstein, Podolsky, and Rosen
      correlations between the angular position and orbital angular momentum of two
      photons created by the nonlinear optical process of spontaneous parametric down
      conversion. The discrete nature of orbital angular momentum and the continuous
      but periodic nature of angular position give rise to a special sort of
      entanglement between these two variables. The resulting correlations are found to
      be an order of magnitude stronger than those allowed by the uncertainty principle
      for independent (nonentangled) particles. Our results suggest that angular
      position and orbital angular momentum may find important applications in quantum
      information science.

PMID- 20689016
TI  - An emerging disease causes regional population collapse of a common North
      American bat species.
AB  - White-nose syndrome (WNS) is an emerging disease affecting hibernating bats in
      eastern North America that causes mass mortality and precipitous population
      declines in winter hibernacula. First discovered in 2006 in New York State, WNS
      is spreading rapidly across eastern North America and currently affects seven
      species. Mortality associated with WNS is causing a regional population collapse
      and is predicted to lead to regional extinction of the little brown myotis
      (Myotis lucifugus), previously one of the most common bat species in North
      America. Novel diseases can have serious impacts on naive wildlife populations,
      which in turn can have substantial impacts on ecosystem integrity.

PMID- 20689019
TI  - Profiling of the compounds absorbed in human plasma and urine after oral
      administration of a traditional Japanese (kampo) medicine, daikenchuto.
AB  - Daikenchuto (DKT), a pharmaceutical-grade traditional Japanese (Kampo) medicine,
      has been widely used for the treatment of various gastrointestinal disorders
      including postoperative ileus and has been integrated into the modern medical
      care system in Japan as a prescription drug. DKT is a multiherbal medicine
      consisting of Japanese pepper (zanthoxylum fruit), processed ginger, and ginseng
      with maltose as an additive. Despite substantial research on the pharmacological
      activities of DKT and its ingredients, the lack of studies on absorption,
      distribution, metabolism, and excretion of DKT has made it difficult to obtain a
      consistent picture of its mechanism of action. In the present study, we
      constructed an analysis procedure consisting of seven conditions of liquid
      chromatography and mass spectrometric analysis, which enabled the identification
      of 44 ingredients of DKT component herbs. We investigated the plasma and urine
      profiles of these ingredients 0.5 to 8 h after oral administration of 15.0 g of
      DKT in four healthy volunteers. The results indicated that 1) hydroxy-alpha
      sanshool and [6]-shogaol, the prominent peaks in plasma derived from Japanese
      pepper and ginger, respectively, were detected at 0.5 h and thereafter decreased
      throughout the sampling period; 2) ginsenoside Rb(1), a prominent peak derived
      from ginseng, increased gradually during the sampling period; 3) glucuronide
      conjugates of hydroxy-sanshools, shogaols, and gingerols were detected in plasma
      and urine; and 4) no obvious differences between samples from the two male and
      the two female individuals were observed. These results provide a strong basis
      for future studies on pharmacokinetics and pharmacology of DKT.

PMID- 20689017
TI  - Nonlinear elasticity and an 8-nm working stroke of single myosin molecules in
      myofilaments.
AB  - Using optical trapping and fluorescence imaging techniques, we measured the step
      size and stiffness of single skeletal myosins interacting with actin filaments
      and arranged on myosin-rod cofilaments that approximate myosin mechanics during
      muscle contraction. Stiffness is dramatically lower for negatively compared to
      positively strained myosins, consistent with buckling of myosin's subfragment 2
      rod domain. Low stiffness minimizes drag of negatively strained myosins during
      contraction at loaded conditions. Myosin's elastic portion is stretched during
      active force generation, reducing apparent step size with increasing load, even
      though the working stroke is approximately constant at about 8 nanometers. Taking
      account of the nonlinear nature of myosin elasticity is essential to relate
      myosin's internal structural changes to physiological force generation and
      filament sliding.

PMID- 20689020
TI  - GPCRs, G-proteins, effectors and their interactions: human-gpDB, a database
      employing visualization tools and data integration techniques.
AB  - G-protein coupled receptors (GPCRs) are a major family of membrane receptors in
      eukaryotic cells. They play a crucial role in the communication of a cell with
      the environment. Ligands bind to GPCRs on the outside of the cell, activating
      them by causing a conformational change, and allowing them to bind to G-proteins.
      Through their interaction with G-proteins, several effector molecules are
      activated leading to many kinds of cellular and physiological responses. The
      great importance of GPCRs and their corresponding signal transduction pathways is
      indicated by the fact that they take part in many diverse disease processes and
      that a large part of efforts towards drug development today is focused on them.
      We present Human-gpDB, a database which currently holds information about 713
      human GPCRs, 36 human G-proteins and 99 human effectors. The collection of
      information about the interactions between these molecules was done manually and
      the current version of Human-gpDB holds information for about 1663 connections
      between GPCRs and G-proteins and 1618 connections between G-proteins and
      effectors. Major advantages of Human-gpDB are the integration of several external
      data sources and the support of advanced visualization techniques. Human-gpDB is
      a simple, yet a powerful tool for researchers in the life sciences field as it
      integrates an up-to-date, carefully curated collection of human GPCRs, G
      proteins, effectors and their interactions. The database may be a reference guide
      for medical and pharmaceutical research, especially in the areas of understanding
      human diseases and chemical and drug discovery. Database URLs:
      http://schneider.embl.de/human_gpdb;
      http://bioinformatics.biol.uoa.gr/human_gpdb/

PMID- 20689015
TI  - Host phylogeny constrains cross-species emergence and establishment of rabies
      virus in bats.
AB  - For RNA viruses, rapid viral evolution and the biological similarity of closely
      related host species have been proposed as key determinants of the occurrence and
      long-term outcome of cross-species transmission. Using a data set of hundreds of
      rabies viruses sampled from 23 North American bat species, we present a general
      framework to quantify per capita rates of cross-species transmission and
      reconstruct historical patterns of viral establishment in new host species using
      molecular sequence data. These estimates demonstrate diminishing frequencies of
      both cross-species transmission and host shifts with increasing phylogenetic
      distance between bat species. Evolutionary constraints on viral host range
      indicate that host species barriers may trump the intrinsic mutability of RNA
      viruses in determining the fate of emerging host-virus interactions.

PMID- 20689021
TI  - GeneCards Version 3: the human gene integrator.
AB  - GeneCards (www.genecards.org) is a comprehensive, authoritative compendium of
      annotative information about human genes, widely used for nearly 15 years. Its
      gene-centric content is automatically mined and integrated from over 80 digital
      sources, resulting in a web-based deep-linked card for each of >73,000 human gene
      entries, encompassing the following categories: protein coding, pseudogene, RNA
      gene, genetic locus, cluster and uncategorized. We now introduce GeneCards
      Version 3, featuring a speedy and sophisticated search engine and a revamped,
      technologically enabling infrastructure, catering to the expanding needs of
      biomedical researchers. A key focus is on gene-set analyses, which leverage
      GeneCards' unique wealth of combinatorial annotations. These include the
      GeneALaCart batch query facility, which tabulates user-selected annotations for
      multiple genes and GeneDecks, which identifies similar genes with shared
      annotations, and finds set-shared annotations by descriptor enrichment analysis.
      Such set-centric features address a host of applications, including microarray
      data analysis, cross-database annotation mapping and gene-disorder associations
      for drug targeting. We highlight the new Version 3 database architecture, its
      multi-faceted search engine, and its semi-automated quality assurance system.
      Data enhancements include an expanded visualization of gene expression patterns
      in normal and cancer tissues, an integrated alternative splicing pattern display,
      and augmented multi-source SNPs and pathways sections. GeneCards now provides
      direct links to gene-related research reagents such as antibodies, recombinant
      proteins, DNA clones and inhibitory RNAs and features gene-related drugs and
      compounds lists. We also portray the GeneCards Inferred Functionality Score
      annotation landscape tool for scoring a gene's functional information status.
      Finally, we delineate examples of applications and collaborations that have
      benefited from the GeneCards suite. Database URL: www.genecards.org.

PMID- 20689022
TI  - Recognition of rapid speech by blind and sighted older adults.
AB  - PURPOSE: To determine whether older blind participants recognize time-compressed
      speech better than older sighted participants. METHOD: Three groups of adults
      with normal hearing participated (n = 10/group): (a) older sighted, (b) older
      blind, and (c) younger sighted listeners. Low-predictability sentences that were
      uncompressed (0% time compression ratio [TCR]) and compressed at 3 rates (40%,
      50%, and 60% TCR) were presented to listeners in quiet and noise. RESULTS: Older
      blind listeners recognized all time-compressed speech stimuli significantly
      better than did older sighted listeners in quiet. In noise, the older blind
      adults recognized the uncompressed and 40% TCR speech stimuli better than did the
      older sighted adults. Performance differences between the younger sighted adults
      and older blind adults were not observed. CONCLUSIONS: The findings support the
      notion that older blind adults recognize time-compressed speech considerably
      better than older sighted adults in quiet and noise. Their performance levels are
      similar to those of younger adults, suggesting that age-related difficulty in
      understanding time-compressed speech is not an inevitable consequence of aging.
      Instead, frequent listening to speech at rapid rates, which was highly correlated
      with performance of the older blind adults, may be a useful technique to minimize
      age-related slowing in speech understanding.

PMID- 20689023
TI  - The CHAPS, SIFTER, and TAPS-R as predictors of (C)AP skills and (C)APD.
AB  - PURPOSE: In this study, the authors investigated the relationships between 3
      tests used to screen for (central) auditory processing disorder ([C]APD)--the
      Children's Auditory Performance Scale (CHAPS; W. J. Smoski, M. A. Brunt, & J. C.
      Tannahill, 1998), the Screening Instrument for Targeting Educational Risk
      (SIFTER; K. Anderson, 1989), and the Test of Auditory Perceptual Skills--Revised
      (TAPS-R; M. Y. Gardner, 1997)-and 4 tests used to diagnostically assess for
      (C)APD: Low-Pass Filtered Speech (LPFS), Competing Sentences (CS), Two-Pair
      Dichotic Digits (DD), and Frequency Patterns With Linguistic Report (FP). METHOD:
      The screening and diagnostic (C)APD tests results of 104 children (71 boys, 33
      girls) aged 6.9-14.3 years were reviewed following their attendance at a
      university clinic in Brisbane, Australia. RESULTS: Pearson's product-moment
      correlation coefficient analysis showed weak (r = .22, p < .05) to moderate (r =
      .47, p < .01) correlations predominantly between the short-term and working
      memory test results of the TAPS-R and the DD and FP test results of the (C)AP
      test battery. Linear and binary logistic regression analyses showed a poor
      ability of the CHAPS, SIFTER, and TAPS-R test results to predict the individual
      LPFS, CS, DD, or FP test results or the overall risk for (C)APD. CONCLUSION: The
      CHAPS, SIFTER, and TAPS-R should be used to highlight concerns about a child but
      not to determine whether a diagnostic (C)AP assessment is particularly warranted.

PMID- 20689024
TI  - The effectiveness of clear speech as a masker.
AB  - PURPOSE: It is established that speaking clearly is an effective means of
      enhancing intelligibility. Because any signal-processing scheme modeled after
      known acoustic-phonetic features of clear speech will likely affect both target
      and competing speech, it is important to understand how speech recognition is
      affected when a competing speech signal is also spoken clearly. In 2 experiments,
      the authors investigated whether listeners would experience improved
      intelligibility when both target and nontarget speech were spoken clearly.
      METHOD: Listeners' recognition of sentences in competing sounds was examined in 2
      experiments. For both experiments, the target speech was spoken in conversational
      and clear styles. The competing sounds in Experiment 1 included 2-talker maskers
      spoken in conversational and clear styles of English or Croatian. The competing
      sounds in Experiment 2 included 1-talker maskers spoken in clear or
      conversational styles and temporally modulated white noise maskers shaped to
      mimic the 1-talker maskers. RESULTS: Performance increased for clear versus
      conversational targets. No significant differences were found between
      conversational and clear maskers. CONCLUSIONS: If it were possible to implement
      clear speech through a listening device, it appears that listeners would still
      receive a clear-speech benefit, even if all sounds (including competing sounds)
      were (inadvertently) processed to be more clear.

PMID- 20689025
TI  - Influence of broad auditory tuning on across-frequency integration of speech
      patterns.
AB  - PURPOSE: The purpose of the present study was to assess whether diminished
      tolerance for disruptions to across-frequency timing in listeners with hearing
      impairment can be attributed to broad auditory tuning. METHOD: In 2 experiments
      in which random assignment was used, sentences were represented as 3 noise bands
      centered at 530, 1500, and 4243 Hz, which were amplitude modulated by 3
      corresponding narrow speech bands. To isolate broad tuning from other influences
      of hearing impairment, listeners with normal hearing (45 in Experiment 1 and 30
      in Experiment 2) were presented with these vocoder stimuli, having carrier band
      filter slopes of 12, 24, and 192 dB/octave. These speech patterns were presented
      in synchrony and with between-band asynchronies up to 40 ms. RESULTS: Mean
      intelligibility scores were reduced in conditions of severe, but not moderate,
      simulated broadening. Although scores fell as asynchrony increased, the steeper
      drop in performance characteristic of listeners with hearing impairment tested
      previously was not observed in conditions of simulated broadening. CONCLUSIONS:
      The intolerance for small across-frequency asynchronies observed previously does
      not appear attributable to broad tuning. Instead, the present data suggest that
      the across-frequency processing mechanism in at least some listeners with hearing
      impairment might be less robust to this type of degradation.

PMID- 20689026
TI  - Effects of aging and noise on real-time spoken word recognition: evidence from
      eye movements.
AB  - PURPOSE: To use eye tracking to investigate age differences in real-time lexical
      processing in quiet and in noise in light of the fact that older adults find it
      more difficult than younger adults to understand conversations in noisy
      situations. METHOD: Twenty-four younger and 24 older adults followed spoken
      instructions referring to depicted objects, for example, "Look at the candle."
      Eye movements captured listeners' ability to differentiate the target noun
      (candle) from a similar-sounding phonological competitor (e.g., candy or sandal).
      Manipulations included the presence/absence of noise, the type of phonological
      overlap in target-competitor pairs, and the number of syllables. RESULTS: Having
      controlled for age-related differences in word recognition accuracy (by tailoring
      noise levels), similar online processing profiles were found for younger and
      older adults when targets were discriminated from competitors that shared onset
      sounds. Age-related differences were found when target words were differentiated
      from rhyming competitors and were more extensive in noise. CONCLUSIONS: Real-time
      spoken word recognition processes appear similar for younger and older adults in
      most conditions; however, age-related differences may be found in the
      discrimination of rhyming words (especially in noise), even when there are no age
      differences in word recognition accuracy. These results highlight the utility of
      eye movement methodologies for studying speech processing across the life span.

PMID- 20689027
TI  - Measuring the effects of reverberation and noise on sentence intelligibility for
      hearing-impaired listeners.
AB  - PURPOSE: The Speech Transmission Index (STI; Houtgast, Steeneken, & Plomp, 1980;
      Steeneken & Houtgast, 1980) is commonly used to quantify the adverse effects of
      reverberation and stationary noise on speech intelligibility for normal-hearing
      listeners. Duquesnoy and Plomp (1980) showed that the STI can be applied for
      presbycusic listeners, relating speech reception thresholds (SRTs) in various
      reverberant conditions to a fixed, subject-dependent STI value. The current study
      aims at extending their results to a wider range of hearing-impaired listeners.
      METHOD: A reverberant analogue of the SRT is presented--the speech reception
      reverberation threshold (SRRT)--which determines the amount of reverberation that
      a listener can sustain to understand 50% of the presented sentences. SRTs are
      performed and evaluated in terms of STI for 5 normal-hearing participants and 36
      randomly selected hearing-impaired participants. RESULTS: Results show that
      differences in STI between reverberant and noisy conditions are only small,
      equivalent to a change in speech-to-noise ratio < 1.3 dB. CONCLUSION: The STI
      appears to be a convenient, single number to quantify speech reception of hearing
      impaired listeners in noise and/or reverberation, regardless of the nature of the
      hearing loss. In future research, the SRRT may be applied to further investigate
      the supposed importance of cognitive processing in reverberant listening
      conditions.

PMID- 20689028
TI  - Assessing multimodal spoken word-in-sentence recognition in children with normal
      hearing and children with cochlear implants.
AB  - PURPOSE: To examine multimodal spoken word-in-sentence recognition in children.
      METHOD: Two experiments were undertaken. In Experiment 1, the youngest age with
      which the multimodal sentence recognition materials could be used was evaluated.
      In Experiment 2, lexical difficulty and presentation modality effects were
      examined, along with test-retest reliability and validity in normal-hearing
      children and those with cochlear implants. RESULTS: Normal-hearing children as
      young as 3.25 years and those with cochlear implants just under 4 years who have
      used their device for at least 1 year were able to complete the multimodal
      sentence testing. Both groups identified lexically easy words in sentences more
      accurately than lexically hard words across modalities, although the largest
      effects occurred in the auditory-only modality. Both groups displayed audiovisual
      integration with the highest scores achieved in the audiovisual modality,
      followed sequentially by auditory-only and visual-only modalities. Recognition of
      words in sentences was correlated with recognition of words in isolation.
      Preliminary results suggest fair-to-good test-retest reliability. CONCLUSIONS:
      The results suggest that children's audiovisual word-in-sentence recognition can
      be assessed using the materials developed for this investigation. With further
      development, the materials hold promise for becoming a test of multimodal
      sentence recognition for children with hearing loss.

PMID- 20689029
TI  - Listening habits of iPod users.
AB  - PURPOSE: To estimate real-environment iPod listening levels for listeners in 4
      environments to gain insight into whether average listeners receive dosages
      exceeding occupational noise exposure guidelines as a result of their listening
      habits. METHOD: The earbud outputs of iPods were connected directly into the
      inputs of a digital recorder to make recordings of listening levels. These
      recordings were used to estimate listening levels using reference recordings made
      in a real ear. Recordings were made in 4 environments with a wide range of
      background noises: (a) a library, (b) a student center, (c) busy streets, and (d)
      the subway. RESULTS: None of the 64 listeners were estimated to exceed allowable
      occupational dosages, with a maximum dose of 7.57% based on Occupational Safety
      and Health Administration (OSHA; 1998) methods and 10.83% based on National
      Institute for Occupational Safety and Health (NIOSH; 1998) methods. CONCLUSIONS:
      All of the listeners surveyed were exposed to dosages well below OSHA and NIOSH
      occupational regulations. Although this does not guarantee individual safety, the
      results do not support the widespread concern regarding the safety of common iPod
      usage. However, measurements made in this study agree with the finding that iPod
      output can exceed safe levels and further support recommendations to monitor and
      limit listening volume and listening duration.

PMID- 20689030
TI  - Speech production accuracy and variability in young cochlear implant recipients:
      comparisons with typically developing age-peers.
AB  - PURPOSE: The speech production accuracy and variability scores of 6 young
      cochlear implant (CI) recipients with 2 years of device experience were compared
      with those of typically developing (TD) age-peers. METHOD: Words from the First
      Words Speech Test (FWST; Ertmer, 1999) were imitated 3 times to assess the
      accuracy and variability of initial consonants, vowels, and words. The initial
      consonants in the 4 sets of the FWST followed a typical order of development.
      RESULTS: The TD group produced targets with high accuracy and low variability.
      Their scores across FWST sets reflected the expected order of development. The CI
      group produced most targets less accurately and with more variability than the TD
      children. Relatively high accuracy for the consonants of Sets 1 and 2 indicated
      that these phonemes were acquired early and in a typical developmental order. A
      trend toward greater accuracy for Set 4 as compared with Set 3 suggested that
      later-emerging consonants were not acquired in the expected order. Variability
      was greatest for later-emerging initial consonants and whole words. DISCUSSION:
      Although considerable speech production proficiency was evident, age-level
      performance was not attained after 2 years of CI experience. Factors that might
      influence the order of consonant acquisition are discussed.

PMID- 20689031
TI  - Use of acoustic cues by children with cochlear implants.
AB  - PURPOSE: This study examined the use of different acoustic cues in auditory
      perception of consonant and vowel contrasts by profoundly deaf children with a
      cochlear implant (CI) in comparison to age-matched children and young adults with
      normal hearing. METHOD: A speech sound categorization task in an XAB format was
      administered to 15 children ages 5-6 with a CI (mean age at implant: 1;8
      [years;months]), 20 normal-hearing age-matched children, and 21 normal-hearing
      adults. Four contrasts were examined: //-/a/, /i/-/i/, /bu/-/pu/, and /fu/-/su/.
      Measures included phoneme endpoint identification, individual cue reliance, cue
      weighting, and classification slope. RESULTS: The children with a CI used the
      spectral cues in the /fu/-/su/ contrast less effectively than the children with
      normal hearing, resulting in poorer phoneme endpoint identification and a
      shallower classification slope. Performance on the other 3 contrasts did not
      differ significantly. Adults consistently showed steeper classification slopes
      than the children, but similar cue-weighting patterns were observed in all 3
      groups. CONCLUSIONS: Despite their different auditory input, children with a CI
      appear to be able to use many acoustic cues effectively in speech perception.
      Most importantly, children with a CI and normal-hearing children were observed to
      use similar cue-weighting patterns.

PMID- 20689032
TI  - Communication, listening, cognitive and speech perception skills in children with
      auditory processing disorder (APD) or Specific Language Impairment (SLI).
AB  - PURPOSE: Parental reports of communication, listening, and behavior in children
      receiving a clinical diagnosis of specific language impairment (SLI) or auditory
      processing disorder (APD) were compared with direct tests of intelligence,
      memory, language, phonology, literacy, and speech intelligibility. The primary
      aim was to identify whether there were differences between these characteristics
      in children with SLI or APD. METHOD: Normally hearing children who were
      clinically diagnosed with SLI (n = 22) or APD (n = 19), and a quasirandom sample
      of mainstream school (MS) children (n = 47) aged 6-13 years, underwent tests of
      verbal and nonverbal IQ, digit span, nonsense word repetition, Spoonerisms,
      reading, grammar, and sentence and VCV nonword intelligibility. Parents completed
      questionnaires on the children's communication, listening, and behavior. RESULTS:
      There was generally no difference between the performance of the children with
      SLI and the children with APD on the questionnaire and test measures, and both
      groups consistently and significantly underperformed compared with the children
      in the MS group. Speech intelligibility in both noise and quiet was unimpaired in
      the SLI and APD groups. CONCLUSION: Despite clinical diagnoses of SLI or APD, the
      2 groups of children had very similar behavioral and parental report profiles,
      suggesting that the children were differentially diagnosed based on their
      referral route rather than on actual differences.

PMID- 20689034
TI  - Dichotic word recognition in noise and the right-ear advantage.
AB  - PURPOSE: This study sought to compare dichotic right-ear advantages (REAs) of
      young adults to older adult data (C. M. Roup, T. L. Wiley, & R. H. Wilson, 2006)
      after matching for overall levels of recognition performance. Specifically,
      speech-spectrum noise was introduced in order to reduce dichotic recognition
      performance of young adults to a level consistent with that of older adults with
      hearing loss. METHOD: Dichotic word-recognition performance was evaluated in the
      free-recall response paradigm across 2 conditions: (a) quiet and (b) noise (+11
      dB signal-to-noise ratio). Participants included a group of right-handed young
      adults (n = 32) with normal hearing. RESULTS: The introduction of noise resulted
      in significantly poorer dichotic word-recognition performance than in the quiet
      condition for the young adults. REAs, however, did not differ between the 2
      conditions. Relative to the Roup et al. (2006) older adult data, performance of
      the young adults in the noise condition resulted in (a) similar levels of overall
      recognition performance and (b) significantly smaller REAs. CONCLUSIONS: Results
      suggest that the magnitude of the REA is not dependent upon the difficulty of the
      dichotic task. Rather, the large REAs exhibited by older adults are more likely
      related to age-related deficits in auditory processing.

PMID- 20689033
TI  - Noise exposure estimates of urban MP3 player users.
AB  - PURPOSE: To examine the sound level and duration of use of personal listening
      devices (PLDs) by 189 college students, ages 18-53 years, as they entered a New
      York City college campus, to determine whether noise exposure from PLDs was in
      excess of recommended exposure limits and what factors might influence exposure.
      METHOD: Free-field equivalent sound levels from PLD headphones were measured on a
      mannequin with a calibrated sound level meter. Participants reported demographic
      information, whether they had just come off the subway, the type of PLD and
      earphones used, and duration per day and days per week they used their PLDs.
      RESULTS: Based on measured free-field equivalent sound levels from PLD headphones
      and the reported PLD use, per day 58.2% of participants exceeded 85 dB A-weighted
      8-hr equivalent sound levels (L(Aeq)), and per week 51.9% exceeded 85 dB A
      weighted 40-hr equivalent continuous sound levels (L(Awkn)). CONCLUSIONS: The
      majority of PLD users exceeded recommended sound exposure limits, suggesting that
      they were at increased risk for noise-induced hearing loss. Analyses of the
      demographics of these participants and mode of transportation to campus failed to
      indicate any particular gender differences in PLD use or in mode of
      transportation influencing sound exposure.

PMID- 20689035
TI  - Spanish/English bilingual listeners on clinical word recognition tests: what to
      expect and how to predict.
AB  - PURPOSE: The current study was an attempt to provide initial evidence on how to
      predict the optimal language in which to conduct speech perception testing for
      Spanish/English (S/E) bilingual listeners. METHOD: Thirty normal-hearing S/E
      listeners differing in age of language acquisition, length of immersion, daily
      language use, self-rated listening proficiency, and language dominance were
      evaluated on the English and Spanish word recognition tests in quiet and in
      speech-spectrum noise. RESULTS: Performance on the English and Spanish tests was
      not correlated for any conditions. English word recognition was most
      significantly correlated with age of English acquisition. Logistic regression
      analyses further demonstrated age of English acquisition to be a good predictor
      of listeners' relative success on the 2 tests in quiet and at +6 dB signal-to
      noise ratio (SNR). At 0 dB SNR, language dominance had the highest predictive
      specificity, whereas the combination of age of English acquisition and Spanish
      listening proficiency had the highest sensitivity. CONCLUSIONS: A Spanish word
      recognition test would likely yield more favorable results for S/E bilingual
      listeners who were Spanish-dominant or who acquired English at 10 years of age or
      older. It may be necessary for listeners who acquired English at 7-10 years of
      age to be evaluated in both English and Spanish.

PMID- 20689037
TI  - Cross-modulation interference with lateralization of mixed-modulated waveforms.
AB  - PURPOSE: This study investigated the ability to use spatial information in mixed
      modulated (MM) sounds containing concurrent frequency-modulated (FM) and
      amplitude-modulated (AM) sounds by exploring patterns of interference when
      different modulation types originated from different loci as may occur in a
      multisource acoustic field. METHOD: Interaural delay thresholds were measured
      from 5 normal-hearing adults for an AM sound in the presence of interfering FM
      and vice versa as a function of interferer modulation rate. In addition, the
      effects of near versus remote interferer rates, and fixed versus randomized
      interferer interaural delay, were investigated. RESULTS: AM interfered with
      lateralization of FM at all modulation rates. However, the FM interfered with AM
      lateralization only when the FM rate was higher than the AM rate. This rate
      asymmetry was surprising given the prevalence of low-frequency dominance in
      lateralization, but was predicted by a cross-correlation model of binaural
      interaction. Effects were similar for fixed and randomized interferer interaural
      delays. CONCLUSIONS: The results suggest that in multisource environments,
      sources containing different modulation types significantly interfere with
      localization in complex ways that reveal interactions between modulation type and
      rate. These findings contribute to the understanding of auditory object formation
      and localization.

PMID- 20689036
TI  - Effects of age on concurrent vowel perception in acoustic and simulated
      electroacoustic hearing.
AB  - PURPOSE: In this study, the authors investigated the effects of age on the use of
      fundamental frequency differences (DeltaF(0)) in the perception of competing
      synthesized vowels in simulations of electroacoustic and cochlear-implant
      hearing. METHOD: Twelve younger listeners with normal hearing and 13 older
      listeners with (near) normal hearing were evaluated in their use of DeltaF(0) in
      the perception of competing synthesized vowels for 3 conditions: unprocessed
      synthesized vowels (UNP), envelope-vocoded synthesized vowels that simulated a
      cochlear implant (VOC), and synthesized vowels processed to simulate
      electroacoustic stimulation (EAS) hearing. Tasks included (a) multiplicity, which
      required listeners to identify whether a stimulus contained 1 or 2 sounds and (b)
      double-vowel identification, which required listeners to attach phonemic labels
      to the competing synthesized vowels. RESULTS: Multiplicity perception was
      facilitated by DeltaF(0) in UNP and EAS but not in VOC, with no age-related
      deficits evident. Double-vowel identification was facilitated by DeltaF(0), with
      DeltaF(0) benefit largest in UNP, reduced in EAS, and absent in VOC. Age
      adversely affected overall identification and DeltaF(0) benefit on the double
      vowel task. CONCLUSIONS: Some but not all older listeners derived DeltaF(0)
      benefit in EAS hearing. This variability may partly be due to how listeners are
      able to draw on higher-level processing resources in extracting and integrating
      cues in EAS hearing.

PMID- 20689038
TI  - The relationship between brainstem temporal processing and performance on tests
      of central auditory function in children with reading disorders.
AB  - PURPOSE: Studies using speech stimuli to elicit electrophysiologic responses have
      found approximately 30% of children with language-based learning problems
      demonstrate abnormal brainstem timing. Research is needed regarding how these
      responses relate to performance on behavioral tests of central auditory function.
      The purpose of the study was to investigate performance of children with dyslexia
      with and without abnormal brainstem timing and children with no history of
      learning or related disorders on behavioral tests of central auditory function.
      METHOD: Performance of 30 school-age children on behavioral central auditory
      tests in common clinical use was examined: Group 1 (n = 10): dyslexia, abnormal
      brainstem timing; Group 2 (n = 10): dyslexia, normal brainstem timing; Group 3 (n
      = 10): typical controls. RESULTS: Results indicated that all participants in
      Group 2 met diagnostic criteria for (central) auditory processing disorder
      [(C)APD], whereas only 4 participants in Group 1 met criteria. The Biological
      Marker of Auditory Processing (BioMARK) identified 6 children in Group 1 who did
      not meet diagnostic criteria for (C)APD but displayed abnormal brainstem timing.
      CONCLUSIONS: Results underscore the importance of central auditory assessment for
      children with dyslexia. Furthermore, the BioMARK may be useful in identifying
      children with central auditory dysfunction who would not have been identified
      using behavioral methods of (C)APD assessment.

PMID- 20689039
TI  - Adult testicular dysgenesis of Inhba conditional knockout mice may also be caused
      by disruption of cross-talk between Leydig cells and germ cells.

PMID- 20689041
TI  - Symmetry and dynamics of molecular rotors in amphidynamic molecular crystals.
AB  - Rotary biomolecular machines rely on highly symmetric supramolecular structures
      with rotating units that operate within a densely packed frame of reference,
      stator, embedded within relatively rigid membranes. The most notable examples are
      the enzyme FoF1 ATP synthase and the bacterial flagellum, which undergo rotation
      in steps determined by the symmetries of their rotators and rotating units.
      Speculating that a precise control of rotational dynamics in rigid environments
      will be essential for the development of artificial molecular machines, we
      analyzed the relation between rotational symmetry order and equilibrium
      rotational dynamics in a set of crystalline molecular gyroscopes with rotators
      having axial symmetry that ranges from two- to fivefold. The site exchange
      frequency for these molecules in their closely related crystals at ambient
      temperature varies by several orders of magnitude, up to ca. 4.46 x 10(8) s(-1).

PMID- 20689042
TI  - In vitro and in vivo reconstitution of the cadherin-catenin-actin complex from
      Caenorhabditis elegans.
AB  - The ternary complex of cadherin, beta-catenin, and alpha-catenin regulates actin
      dependent cell-cell adhesion. alpha-Catenin can bind beta-catenin and F-actin,
      but in mammals alpha-catenin either binds beta-catenin as a monomer or F-actin as
      a homodimer. It is not known if this conformational regulation of alpha-catenin
      is evolutionarily conserved. The Caenorhabditis elegans alpha-catenin homolog HMP
      1 is essential for actin-dependent epidermal enclosure and embryo elongation.
      Here we show that HMP-1 is a monomer with a functional C-terminal F-actin binding
      domain. However, neither full-length HMP-1 nor a ternary complex of HMP-1-HMP
      2(beta-catenin)-HMR-1(cadherin) bind F-actin in vitro, suggesting that HMP-1 is
      auto-inhibited. Truncation of either the F-actin or HMP-2 binding domain of HMP-1
      disrupts C. elegans development, indicating that HMP-1 must be able to bind F
      actin and HMP-2 to function in vivo. Our study defines evolutionarily conserved
      properties of alpha-catenin and suggests that multiple mechanisms regulate alpha
      catenin binding to F-actin.

PMID- 20689043
TI  - Structure and mechanism of proton transport through the transmembrane tetrameric
      M2 protein bundle of the influenza A virus.
AB  - The M2 proton channel from influenza A virus is an essential protein that
      mediates transport of protons across the viral envelope. This protein has a
      single transmembrane helix, which tetramerizes into the active channel. At the
      heart of the conduction mechanism is the exchange of protons between the His37
      imidazole moieties of M2 and waters confined to the M2 bundle interior. Protons
      are conducted as the total charge of the four His37 side chains passes through
      2(+) and 3(+) with a pK(a) near 6. A 1.65 A resolution X-ray structure of the
      transmembrane protein (residues 25-46), crystallized at pH 6.5, reveals a pore
      that is lined by alternating layers of sidechains and well-ordered water
      clusters, which offer a pathway for proton conduction. The His37 residues form a
      box-like structure, bounded on either side by water clusters with well-ordered
      oxygen atoms at close distance. The conformation of the protein, which is
      intermediate between structures previously solved at higher and lower pH,
      suggests a mechanism by which conformational changes might facilitate asymmetric
      diffusion through the channel in the presence of a proton gradient. Moreover,
      protons diffusing through the channel need not be localized to a single His37
      imidazole, but instead may be delocalized over the entire His-box and associated
      water clusters. Thus, the new crystal structure provides a possible unification
      of the discrete site versus continuum conduction models.

PMID- 20689045
TI  - Phonological activation during visual word recognition in deaf and hearing
      children.
AB  - PURPOSE: Phonological activation during visual word recognition was studied in
      deaf and hearing children under two circumstances: (a) when the use of phonology
      was not required for task performance and might even hinder it and (b) when the
      use of phonology was critical for task performance. METHOD: Deaf children
      mastering written Dutch and Sign Language of the Netherlands were compared with
      hearing children. Two word-picture verification experiments were conducted, both
      of which included pseudohomophones. In Experiment 1, the task was to indicate
      whether the word was spelled correctly and whether it corresponded to the
      picture. The presence of pseudohomophones was expected to hinder performance only
      when phonological recoding occurred. In Experiment 2, the task was to indicate
      whether the word sounded like the picture, which now made phonological recoding
      essential in order to enable the acceptance of pseudohomophones. RESULTS: The
      hearing children showed automatic activation of phonology during visual word
      recognition, regardless of whether they were instructed to focus on orthographic
      information (Experiment 1) or phonological information (Experiment 2). The deaf
      children showed little automatic phonological activation in either experiment.
      CONCLUSION: Deaf children do not use phonological information during word
      reading.

PMID- 20689044
TI  - Human origin recognition complex is essential for HP1 binding to chromatin and
      heterochromatin organization.
AB  - The origin recognition complex (ORC) is a DNA replication initiator protein also
      known to be involved in diverse cellular functions including gene silencing,
      sister chromatid cohesion, telomere biology, heterochromatin localization,
      centromere and centrosome activity, and cytokinesis. We show that, in human
      cells, multiple ORC subunits associate with hetereochromatin protein 1 (HP1)
      alpha- and HP1beta-containing heterochromatic foci. Fluorescent bleaching studies
      indicate that multiple subcomplexes of ORC exist at heterochromatin, with Orc1
      stably associating with heterochromatin in G1 phase, whereas other ORC subunits
      have transient interactions throughout the cell-division cycle. Both Orc1 and
      Orc3 directly bind to HP1alpha, and two domains of Orc3, a coiled-coil domain and
      a mod-interacting region domain, can independently bind to HP1alpha; however,
      both are essential for in vivo localization of Orc3 to heterochromatic foci.
      Direct binding of both Orc1 and Orc3 to HP1 suggests that, after the degradation
      of Orc1 at the G1/S boundary, Orc3 facilitates assembly of ORC/HP1 proteins to
      chromatin. Although depletion of Orc2 and Orc3 subunits by siRNA caused loss of
      HP1alpha association to heterochromatin, loss of Orc1 and Orc5 caused aberrant
      HP1alpha distribution only to pericentric heterochromatin-surrounding nucleoli.
      Depletion of HP1alpha from human cells also shows loss of Orc2 binding to
      heterochromatin, suggesting that ORC and HP1 proteins are mutually required for
      each other to bind to heterochromatin. Similar to HP1alpha-depleted cells, Orc2
      and Orc3 siRNA-treated cells also show loss of compaction at satellite repeats,
      suggesting that ORC together with HP1 proteins may be involved in organizing
      higher-order chromatin structure and centromere function.

PMID- 20689046
TI  - Variations in intensity, fundamental frequency, and voicing for teachers in
      occupational versus nonoccupational settings.
AB  - PURPOSE: In this study, the authors created a more concise picture of the vocal
      demands placed on teachers by comparing occupational voice use with
      nonoccupational voice use. METHOD: The authors used National Center for Voice and
      Speech voice dosimetry databank to calculate voicing percentage per hour as well
      as average dB SPL and fundamental frequency (F(0)). Occupational voice use (9:00
      a.m.-3:00 p.m., weekdays) and nonoccupational voice use (4:00 p.m.-10:00 p.m.,
      weekends) were compared (57 teachers, 2 weeks each). RESULTS: Five key findings
      were uncovered: (1) Similar to previous studies, occupational voicing percentage
      per hour is more than twice that of nonoccupational voicing; (2) teachers
      experienced a wide range of occupational voicing percentages per hour (30+/-11%
      per hr); (3) average occupational voice was about 1 dB SPL louder than the
      nonoccupational voice and remained constant throughout the day; (4) occupational
      voice exhibited an increased pitch and trended upward throughout the day; and (5)
      some apparent gender differences were shown. CONCLUSIONS: Data regarding voicing
      percentages, F(0), and dB SPL provide critical insight into teachers' vocal
      health. Further, because nonoccupational voice use is added to an already
      overloaded voice, it may add key insights into recovery patterns and should be
      the focus of future studies.

PMID- 20689047
TI  - Effects of dining on tongue endurance and swallowing-related outcomes.
AB  - PURPOSE: The purpose of this study was to test the hypothesis that eating a meal
      reduces tongue strength and endurance in healthy old and young adults. It was
      predicted that older adults would show greater declines in tongue endurance while
      demonstrating higher perceived effort, longer meal durations, and clinical signs
      of swallowing difficulty. METHOD: Twenty-two healthy adults were enrolled into 2
      groups (ages 20-35 years and ages 65-82 years; 5 males and 6 females each).
      Maximum tongue strength (Pmax) and endurance (duration 50% of Pmax could be
      maintained) were measured twice at baseline and once postmeal. Subjects consumed
      half of a bagel with peanut butter, carrot sticks, and milk between measures.
      RESULTS: All subjects demonstrated reduced tongue strength and endurance
      postmeal. Young adults showed a greater decline in anterior tongue endurance
      compared with older adults (p=.05). There was no evidence that changes in tongue
      strength, perceived effort, or meal duration varied by age or gender. The 3
      oldest subjects reported the highest effort and displayed signs of difficulty
      swallowing while dining. CONCLUSIONS: Young and old adults demonstrated reduced
      tongue strength and endurance after dining, but younger subjects showed greater
      declines in anterior tongue endurance, whereas older adults exhibited signs of
      swallowing difficulty.

PMID- 20689048
TI  - Refutation of a therapeutic alternative? A reply to Pollard, Ellis, Finan, and
      Ramig (2009).
AB  - PURPOSE: To challenge the findings of Pollard, Ellis, Finan, and Ramig (2009),
      who examined 11 participants using the SpeechEasy, an in-the-ear device that
      employs altered auditory feedback to reduce stuttering, in a 6-month "clinical
      trial." Pollard et al. failed to demonstrate a significant treatment effect on
      stuttering frequency, yet found positive subjective self-report data across four
      months of use. The authors concluded that the device was not therapeutically
      useful and further testing is unwarranted. RESULTS: We dispute Pollard et al. on
      the following grounds: Their operational definition of stuttering is confounded
      as it does not adequately distinguish true stuttering from "normally" disfluent
      speech or from volitionally produced initiating gestures taught to be used as
      part of the treatment protocol, nor is it the definition used in their pre- and
      posttreatment stuttering assessment instrument; they failed to maintain
      participant adherence to the treatment protocol of device usage; they utilized an
      inadequate question-asking task; and their conclusion of no significant treatment
      effect that is drawn from their inferential statistical analyses of group data.
      CONCLUSIONS: In light of problematic objective measurements, reported positive
      subjective findings, a robust corpus of contradictory data, and the need for
      alternative stuttering treatments, we argue that the SpeechEasy merits further
      investigation.

PMID- 20689050
TI  - Poster session fundamentals: becoming a proficient "poster child" for health
      education.

PMID- 20689051
TI  - Benefits of professional organization membership and participation in national
      conferences: considerations for students and new professionals.
AB  - The focus of this manuscript is on the next generation of health education
      professionals and is written by those who are part of that next generation. This
      manuscript serves as a good reminder to all health educators regarding the
      importance of professional association membership and attending professional
      conferences. The co-editors hope that established health education professionals
      whether serving as faculty members teaching in professional preparation programs
      or those practitioners mentoring the next generation-will share this article with
      students and/ or colleagues regarding the benefits of attending professional
      conferences and joining professional organizations. Joining professional
      organizations like the Society for Public Health Education (SOPHE) and attending
      professional conferences can provide tremendous career development, skill
      building, and professional networking opportunities.

PMID- 20689052
TI  - The health disparities industry: is it an ethical conundrum?
AB  - Reducing health disparities is the purported mission of a huge network of
      professionals representing many specialties and organizations offering a variety
      of products and services. Given its elaborate infrastructure and specialized set
      of activities, we identity the network as the health disparities industry. In
      this article, we question the ethics of this industry. Specifically, we ask
      whether the public mission is trumped by questionable industry leadership,
      ethics, and quality assurances. Drawing on general principles of ethics and
      differentiating ethical concerns from ethical problems, we conclude that the
      collective behaviors within the industry may represent an ethical conundrum. The
      article concludes with a call for the cross-examination of the industry
      practices.

PMID- 20689053
TI  - Nonbelieved memories.
AB  - This is the first empirical study of vivid autobiographical memories for events
      that people no longer believe happened to them. Until now, this phenomenon has
      been the object of relatively rare, albeit intriguing, anecdotes, such as Jean
      Piaget's description of his vivid memory of an attempted abduction that never
      happened. The results of our study show that nonbelieved memories are much more
      common than is expected. Approximately 20% of our initial sample reported having
      at least one nonbelieved autobiographical memory. Participants' ratings indicate
      that nonbelieved memories share most recollective qualities of believed memories,
      but are characterized by more negative emotions. The results have important
      implications for the way autobiographical memory is conceptualized and for the
      false-memory debate.

PMID- 20689054
TI  - Observation inflation. Your actions become mine.
AB  - Imagining performing an action can induce false memories of having actually
      performed it-this is referred to as the imagination-inflation effect. Drawing on
      research suggesting that action observation-like imagination-involves action
      simulation, and thus creates matching motor representations in observers, we
      examined whether false memories of self-performance can also result from merely
      observing another person's actions. In three experiments, participants observed
      actions, some of which they had not performed earlier, and took a source-memory
      test. Action observation robustly produced false memories of self-performance
      relative to control conditions. The demonstration of this effect, which we refer
      to as observation inflation, reveals a previously unknown source of false
      memories that is ubiquitous in everyday life. The effect persisted despite
      warnings or instructions to focus on self-performance cues given immediately
      before the test, and despite elimination of sensory overlap between performance
      and observation. The findings are not easily reconciled with a source-monitoring
      account but appear to fit an account invoking interpersonal motor simulation.

PMID- 20689055
TI  - Identification of microRNAs during rat liver regeneration after partial
      hepatectomy and modulation by ursodeoxycholic acid.
AB  - New gene regulation study tools such as microRNA (miRNA or miR) analysis may
      provide unique insights into the remarkable ability of the liver to regenerate.
      In addition, we have previously shown that ursodeoxycholic acid (UDCA) modulates
      mRNA levels during liver regeneration. Bile acids are also homeotrophic sensors
      of functional hepatic capacity. The present study was designed to determine
      whether miRNAs are modulated in rats following 70% partial hepatectomy (PH) and
      elucidate the role of UDCA in regulating miRNA expression during liver
      regeneration (LR). Total RNA was isolated from livers harvested at 3-72 h
      following 70% PH or sham operations, from both 0.4% (wt/wt) UDCA and control diet
      fed animals. By using a custom microarray platform we found that several miRNAs
      are significantly altered after PH by >1.5-fold, including some previously
      described as modulators of cell proliferation, differentiation, and death. In
      particular, expression of miR-21 was increased after PH. Functional modulation of
      miR-21 in primary rat hepatocytes increased cell proliferation and viability.
      Importantly, UDCA was a strong inducer of miR-21 both during LR and in cultured
      HepG2 cells. In fact, UDCA feeding appeared to induce a sustained increase of
      proliferative miRNAs observed at early time points after PH. In conclusion,
      miRNAs, in particular miR-21, may play a significant role in modulating
      proliferation and cell cycle progression genes after PH. miR-21 is additionally
      induced by UDCA in both regenerating rat liver and in vitro, which may represent
      a new mechanism behind UDCA biological functions.

PMID- 20689056
TI  - Hypothalamic oxytocin mediates adaptation mechanism against chronic stress in
      rats.
AB  - Accumulation of continuous life stress (chronic stress) often causes gastric
      symptoms. Although central oxytocin has antistress effects, the role of central
      oxytocin in stress-induced gastric dysmotility remains unknown. Solid gastric
      emptying was measured in rats receiving acute restraint stress, 5 consecutive
      days of repeated restraint stress (chronic homotypic stress), and 7 consecutive
      days of varying types of stress (chronic heterotypic stress). Oxytocin and
      oxytocin receptor antagonist were administered intracerebroventricularly (icv).
      Expression of corticotropin-releasing factor (CRF) mRNA and oxytocin mRNA in the
      paraventricular nucleus (PVN) of the hypothalamus was evaluated by real-time RT
      PCR. The changes of oxytocinergic neurons in the PVN were evaluated by
      immunohistochemistry. Acute stress delayed gastric emptying, and the delayed
      gastric emptying was completely restored after 5 consecutive days of chronic
      homotypic stress. In contrast, delayed gastric emptying persisted following
      chronic heterotypic stress. The restored gastric emptying following chronic
      homotypic stress was antagonized by icv injection of an oxytocin antagonist. Icv
      injection of oxytocin restored delayed gastric emptying induced by chronic
      heterotypic stress. CRF mRNA expression, which was significantly increased in
      response to acute stress and chronic heterotypic stress, returned to the basal
      levels following chronic homotypic stress. In contrast, oxytocin mRNA expression
      was significantly increased following chronic homotypic stress. The number of
      oxytocin-immunoreactive cells was increased following chronic homotypic stress at
      the magnocellular part of the PVN. Icv injection of oxytocin reduced CRF mRNA
      expression induced by acute stress and chronic heterotypic stress. It is
      suggested that the adaptation mechanism to chronic stress may involve the
      upregulation of oxytocin expression in the hypothalamus, which in turn attenuates
      CRF expression.

PMID- 20689057
TI  - Loss of protein tyrosine phosphatase N2 potentiates epidermal growth factor
      suppression of intestinal epithelial chloride secretion.
AB  - The Crohn's disease candidate gene, protein tyrosine phosphatase nonreceptor type
      2 (PTPN2), has been shown to regulate epidermal growth factor (EGF)-induced
      phosphatidylinositol 3-kinase (PI3K) activation in fibroblasts. In intestinal
      epithelial cells (IECs), EGF-induced EGF receptor (EGFR) activation and
      recruitment of PI3K play a key role in regulating many cellular functions
      including Ca(2+)-dependent Cl(-) secretion. Moreover, EGFR also serves as a
      conduit for signaling by other non-growth factor receptor ligands such as the
      proinflammatory cytokine, IFN-gamma. Here we investigated a possible role for
      PTPN2 in the regulation of EGFR signaling and Ca(2+)-dependent Cl(-) secretion in
      IECs. PTPN2 knockdown enhanced EGF-induced EGFR tyrosine phosphorylation in T(84)
      cells. In particular, PTPN2 knockdown promoted EGF-induced phosphorylation of
      EGFR residues Tyr-992 and Tyr-1068 and led subsequently to increased association
      of the catalytic PI3K subunit, p110, with EGFR and elevated phosphorylation of
      the downstream marker, Akt. As a functional consequence, loss of PTPN2
      potentiated EGF-induced inhibition of carbachol-stimulated Ca(2+)-dependent Cl(-)
      secretion. In contrast, PTPN2 knockdown affected neither IFN-gamma-induced EGFR
      transactivation nor EGF- or IFN-gamma-induced phosphorylation of ERK1/2. In
      summary, our data establish a role for PTPN2 in the regulation of EGFR signaling
      in IECs in response to EGF but not IFN-gamma. Knockdown of PTPN2 directs EGFR
      signaling toward increased PI3K activation and increased suppression of
      epithelial chloride secretory responses. Moreover, our findings suggest that
      PTPN2 dysfunction in IECs leads to altered control of intestinal epithelial
      functions regulated by EGFR.

PMID- 20689058
TI  - Nuclear expression of interleukin-33 in pancreatic stellate cells.
AB  - Activated pancreatic stellate cells (PSCs) play a pivotal role in pancreatic
      fibrosis in chronic pancreatitis and pancreatic cancer. Recent studies have
      suggested a role of IL-33, a newly identified IL-1 family member, in fibrosis. We
      here examined the expression of IL-33 and the IL-33-mediated regulation of cell
      functions in PSCs. PSCs were isolated from human and rat pancreas tissues. The
      expression of IL-33 was examined by Western blotting, PCR, ELISA, and
      immunostaining. The roles of IL-33 in the regulation of PSC functions were
      examined by using recombinant IL-33 and small interfering RNA. Activated PSCs
      expressed IL-33 in the nucleus, and the expression was increased by IL-1beta, TNF
      alpha, PDGF-BB, and IFN-gamma, but not TGF-beta1. Nuclear IL-33 expression was
      also observed in the pancreatic acinar and ductal cells. IL-1beta induced IL-33
      expression mainly through the activation of NF-kappaB and ERK pathways and
      partially through that of p38 MAP kinase, whereas PDGF-BB induced IL-33
      expression mainly through the activation of ERK pathway. PSCs expressed soluble
      ST2, ST2L, and IL-1RAcP, but the expression level of ST2L was relatively low.
      Recombinant IL-33 did not stimulate key cell functions of PSCs. Decreased IL-33
      expression by small interfering RNA resulted in decreased proliferation in
      response to PDGF-BB. In conclusion, activated PSCs expressed IL-33 in the
      nucleus. IL-33 might regulate the PDGF-induced proliferation in PSCs.

PMID- 20689060
TI  - Colon luminal content and epithelial cell morphology are markedly modified in
      rats fed with a high-protein diet.
AB  - Hyperproteic diets are used in human nutrition to obtain body weight reduction.
      Although increased protein ingestion results in an increased transfer of proteins
      from the small to the large intestine, there is little information on the
      consequences of the use of such diets on the composition of large intestine
      content and on epithelial cell morphology and metabolism. Rats were fed for 15
      days with either a normoproteic (NP, 14% protein) or a hyperproteic isocaloric
      diet (HP, 53% protein), and absorptive colonocytes were observed by electron
      microscopy or isolated for enzyme activity studies. The colonic luminal content
      was recovered for biochemical analysis. Absorbing colonocytes were characterized
      by a 1.7-fold reduction in the height of the brush-border membranes (P = 0.0001)
      after HP diet consumption when compared with NP. This coincided in the whole
      colon content of HP animals with a 1.8-fold higher mass content (P = 0.0020), a
      2.2-fold higher water content (P = 0.0240), a 5.2-fold higher protease activity
      (P = 0.0104), a 5.5-fold higher ammonia content (P = 0.0008), and a more than
      twofold higher propionate, valerate, isobutyrate, and isovalerate content (P <
      0.05). The basal oxygen consumption of colonocytes was similar in the NP and HP
      groups, but ammonia was found to provoke a dose-dependent decrease of oxygen
      consumption in the isolated absorbing colonocytes. The activity of glutamine
      synthetase (which condenses ammonia and glutamate) was found to be much higher in
      colonocytes than in small intestine enterocytes and was 1.6-fold higher (P =
      0.0304) in colonocytes isolated from HP animals than NP. Glutaminase activity
      remained unchanged. Thus hyperproteic diet ingestion causes marked changes both
      in the luminal environment of colonocytes and in the characteristics of these
      cells, demonstrating that hyperproteic diet interferes with colonocyte metabolism
      and morphology. Possible causal relationships between energy metabolism, reduced
      height of colonocyte brush-border membranes, and reduced water absorption are
      discussed.

PMID- 20689059
TI  - HIF-1 mediates pathogenic inflammatory responses to intestinal ischemia
      reperfusion injury.
AB  - Acute lung injury (ALI) and the development of the multiple organ dysfunction
      syndrome (MODS) are major causes of death in trauma patients. Gut inflammation
      and loss of gut barrier function as a consequence of splanchnic ischemia
      reperfusion (I/R) have been implicated as the initial triggering events that
      contribute to the development of the systemic inflammatory response, ALI, and
      MODS. Since hypoxia-inducible factor (HIF-1) is a key regulator of the
      physiological and pathophysiological response to hypoxia, we asked whether HIF-1
      plays a proximal role in the induction of gut injury and subsequent lung injury.
      Utilizing partially HIF-1alpha-deficient mice in a global trauma hemorrhagic
      shock (T/HS) model, we found that HIF-1 activation was necessary for the
      development of gut injury and that the prevention of gut injury was associated
      with an abrogation of lung injury. Specifically, in vivo studies demonstrated
      that partial HIF-1alpha deficiency ameliorated T/HS-induced increases in
      intestinal permeability, bacterial translocation, and caspase-3 activation.
      Lastly, partial HIF-1alpha deficiency reduced TNF-alpha, IL-1beta, cyclooxygenase
      2, and inducible nitric oxide synthase levels in the ileal mucosa after T/HS
      whereas IL-1beta mRNA levels were reduced in the lung after T/HS. This study
      indicates that prolonged intestinal HIF-1 activation is a proximal regulator of
      I/R-induced gut mucosal injury and gut-induced lung injury. Consequently, these
      results provide unique information on the initiating events in trauma-hemorrhagic
      shock-induced ALI and MODS as well as potential therapeutic insights.

PMID- 20689061
TI  - Roles of lysosomal proteolytic systems in AQP5 degradation in the submandibular
      gland of rats following chorda tympani parasympathetic denervation.
AB  - Chorda tympani denervation (CTD) of rats was earlier shown to result in loss of
      submandibular gland (SMG) weight (at only 1 wk) and in continued reduction in
      aquaporin 5 (AQP5) protein expression (until 4 wk), without affecting its mRNA
      synthesis (Li X, Azlina A, Karabasil MR, Purwanti N, Hasegawa T, Yao C, Akamatsu
      T, Hosoi K. Am J Physiol Gastrointest Liver Physiol 295: G112-G123, 2008). The
      present study indicated that despite elevation of bax, a proapoptosis protein, by
      CTD, the operation also increased the level of bcl-2, an antiapoptosis protein,
      in the SMG. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL
      assay) showed no increase in the number of apoptotic cells in the SMG. CTD,
      however, induced strongly and transiently (at 1-3 days) the protein expression of
      LC3B-II, a marker protein of autophagosomes, suggesting that the reduction in the
      gland weight was due to onset of autophagy by CTD. Upon CTD, Lamp2, a lysosomal
      marker, gradually increased in amount, reaching a peak at the 14th day.
      Immunohistochemical analysis revealed an increase in the number of lysosome-like
      structures positive for both AQP5 and Lamp2 in the acinar cells of the SMG after
      CTD; similar changes were observed also for AQP5 and LC3Bs. These data suggest
      that AQP5 in the SMG entered autophagosomes and/or lysosomes for degradation upon
      CTD. In vitro AQP5-degrading activity was found in the SMG extracts, and such
      activity was shown to be increased by CTD. Inhibitor experiments implied
      cathepsins B and L to be candidate enzymes for this degradation under normal and
      CTD conditions, respectively.

PMID- 20689062
TI  - Involvement of the brain (pro)renin receptor in cardiovascular homeostasis.
AB  - RATIONALE: Despite overwhelming evidence of the importance of brain renin
      angiotensin system (RAS), the very existence of intrinsic brain RAS remains
      controversial. OBJECTIVE: To investigate the hypothesis that the brain (pro)renin
      receptor (PRR) is physiologically important in the brain RAS regulation and
      cardiovascular functions. METHODS AND RESULTS: PRR is broadly distributed within
      neurons of cardiovascular-relevant brain regions. The physiological functions of
      PRR were studied in the supraoptic nucleus (SON) because this brain region showed
      greater levels of PRR mRNA in the spontaneously hypertensive rats (SHR) compared
      with normotensive Wistar-Kyoto (WKY) rats. Adeno-associated virus (AAV)-mediated
      overexpression of human PRR in the SON of normal rats resulted in increases in
      plasma and urine vasopressin, and decreases in H(2)O intake and urine output
      without any effects on mean arterial pressure and heart rate. Knockdown of
      endogenous PRR by AAV-short hairpin RNA in the SON of SHRs attenuated age
      dependent increases in mean arterial pressure and caused a decrease in heart rate
      and plasma vasopressin. Incubation of neuronal cells in culture with human
      prorenin and angiotensinogen resulted in increased generation of angiotensin I
      and II. Furthermore, renin treatment increased phosphorylation of extracellular
      signal-regulated kinase 1/2 in neurons from both WKY rats and SHRs; however, the
      stimulation was 50% greater in the SHR. CONCLUSIONS: The study demonstrates that
      brain PRR is functional and plays a role in the neural control of cardiovascular
      functions. This may help resolve a long-held controversy concerning the existence
      of intrinsic and functional brain RAS.

PMID- 20689063
TI  - Receptor-independent cardiac protein kinase Calpha activation by calpain-mediated
      truncation of regulatory domains.
AB  - RATIONALE: Protein kinase (PK)Cs and calpain cysteine proteases are highly
      expressed in myocardium. Ischemia produces calcium overload that activates
      calpains and conventional PKCs. However, calpains can proteolytically process
      PKCs, and the potential in vivo consequences of this interaction are unknown.
      OBJECTIVE: To determine the biochemical and pathophysiological consequences of
      calpain-mediated cardiac PKCalpha proteolysis. METHODS AND RESULTS: Isolated
      mouse hearts subjected to global ischemia/reperfusion demonstrated cleavage of
      PKCalpha. Calpain 1 overexpression was not sufficient to produce PKCalpha
      cleavage in normal hearts, but ischemia-induced myocardial PKCalpha cleavage and
      myocardial injury were greatly increased by cardiac-specific expression of
      calpain 1. In contrast, calpain 1 gene ablation or inhibition with calpastatin
      prevented ischemia/reperfusion induced PKCalpha cleavage; infarct size was
      decreased and ventricular function enhanced in infarcted calpain 1 knockout
      hearts. To determine consequences of PKCalpha fragmentation on myocardial protein
      phosphorylation, transgenic mice were created conditionally expressing full
      length PKCalpha or its N-terminal and C-terminal calpain 1 cleavage fragments.
      Two-dimensional mapping of ventricular protein extracts showed a distinct
      PKCalpha phosphorylation profile that was exaggerated and distorted in hearts
      expressing the PKCalpha C-terminal fragment. MALDI mass spectroscopy revealed
      hyperphosphorylation of myosin-binding protein C and phosphorylation of atypical
      substrates by the PKCalpha C-terminal fragment. Expression of parent PKCalpha
      produced a mild cardiomyopathy, whereas myocardial expression of the C-terminal
      PKCalpha fragment induced a disproportionately severe, rapidly lethal
      cardiomyopathy. CONCLUSIONS: Proteolytic processing of PKCalpha by calcium
      activated calpain activates pathological cardiac signaling through generation of
      an unregulated and/or mistargeted kinase. Production of the PKCalpha C-terminal
      fragment in ischemic hearts occurs via a receptor-independent mechanism.

PMID- 20689064
TI  - Notch3 is critical for proper angiogenesis and mural cell investment.
AB  - RATIONALE: The heterotypic interactions of endothelial cells and mural cells
      (smooth muscle cells or pericytes) are crucial for assembly, maturation, and
      subsequent function of blood vessels. Yet, the molecular mechanisms underlying
      their association have not been fully defined. OBJECTIVE: Our previous in vitro
      studies indicated that Notch3, which is expressed in mural cells, mediates these
      cell-cell interactions. To assess the significance of Notch3 on blood vessel
      formation in vivo, we investigated its role in retinal angiogenesis. METHODS AND
      RESULTS: We show that Notch3-deficient mice exhibit reduced retinal
      vascularization, with diminished sprouting and vascular branching. Moreover,
      Notch3 deletion impairs mural cell investment, resulting in progressive loss of
      vessel coverage. In an oxygen-induced retinopathy model, we demonstrate that
      Notch3 is induced in hypoxia and interestingly, pathological neovascularization
      is decreased in retinas of Notch3-null mice. Analysis of oxygen-induced
      retinopathy mediators revealed that angiopoietin-2 expression is significantly
      reduced in the absence of Notch3. Furthermore, in vitro experiments showed that
      Notch3 is sufficient for angiopoietin-2 induction, and this expression is
      additionally enhanced in the presence of hypoxia-inducible factor 1alpha.
      CONCLUSIONS: These results provide compelling evidence that Notch3 is important
      for the investment of mural cells and is a critical regulator of developmental
      and pathological blood vessel formation.

PMID- 20689067
TI  - Does APD gradient indicate dispersion of repolarization ?

PMID- 20689065
TI  - Cardiac small conductance Ca2+-activated K+ channel subunits form heteromultimers
      via the coiled-coil domains in the C termini of the channels.
AB  - RATIONALE: Ca(2+)-activated K(+) channels are present in a wide variety of cells.
      We have previously reported the presence of small conductance Ca(2+)-activated
      K(+) (SK or K(Ca)) channels in human and mouse cardiac myocytes that contribute
      functionally toward the shape and duration of cardiac action potentials. Three
      isoforms of SK channel subunits (SK1, SK2, and SK3) are found to be expressed.
      Moreover, there is differential expression with more abundant SK channels in the
      atria and pacemaking tissues compared with the ventricles. SK channels are
      proposed to be assembled as tetramers similar to other K(+) channels, but the
      molecular determinants driving their subunit interaction and assembly are not
      defined in cardiac tissues. OBJECTIVE: To investigate the heteromultimeric
      formation and the domain necessary for the assembly of 3 SK channel subunits
      (SK1, SK2, and SK3) into complexes in human and mouse hearts. METHODS AND
      RESULTS: Here, we provide evidence to support the formation of heteromultimeric
      complexes among different SK channel subunits in native cardiac tissues. SK1,
      SK2, and SK3 subunits contain coiled-coil domains (CCDs) in the C termini. In
      vitro interaction assay supports the direct interaction between CCDs of the
      channel subunits. Moreover, specific inhibitory peptides derived from CCDs block
      the Ca(2+)-activated K(+) current in atrial myocytes, which is important for
      cardiac repolarization. CONCLUSIONS: The data provide evidence for the formation
      of heteromultimeric complexes among different SK channel subunits in atrial
      myocytes. Because SK channels are predominantly expressed in atrial myocytes,
      specific ligands of the different isoforms of SK channel subunits may offer a
      unique therapeutic opportunity to directly modify atrial cells without
      interfering with ventricular myocytes.

PMID- 20689069
TI  - Jeffrey Robbins: does not do discouragement.

PMID- 20689070
TI  - Unraveling enigma in the z-disks.

PMID- 20689071
TI  - Epigenetic regulation of the cardiovascular system: introduction to a review
      series.

PMID- 20689073
TI  - Phosphorylation of G protein-coupled receptor kinase 2-interacting protein 1
      tyrosine 392 is required for phospholipase C-gamma activation and podosome
      formation in vascular smooth muscle cells.
AB  - OBJECTIVE: Podosomes, which are actin-rich structures, contribute to cell
      motility, matrix remodeling, and tissue remodeling. We have shown that G protein
      coupled receptor kinase 2-interacting protein 1 (GIT1) colocalizes with podosomes
      and is important in podosome formation in endothelial cells. Src stimulates GIT1
      tyrosine phosphorylation, which is critical for phospholipase C-gamma (PLCgamma)
      activation. In this study, we identified specific GIT1 tyrosines required for
      PLCgamma activation and podosome formation in vascular smooth muscle cells
      (VSMC). METHODS AND RESULTS: We used phorbol 12,13-dibutyrate (PDBU) to induce
      podosomes in A7r5 VSMC. GIT1 colocalized with podosomes and GIT1 knockdown using
      short interfering RNA significantly reduced podosome formation. PDBU stimulated
      GIT1 tyrosine phosphorylation. GIT1 tyrosine phosphorylation was dramatically
      decreased in SYF-/- cells, and it was also reduced by pretreatment with the
      protein kinase C (PKC) and Src inhibitors, suggesting that GIT1 phosphorylation
      was dependent on PKC and Src. By mutation analysis of multiple tyrosines, we
      found that PDBU specifically increased GIT1-Y392 phosphorylation. Overexpression
      of GIT1 (Y392F) but not of GIT1 (Y321F) decreased PDBU-mediated PLCgamma
      activation and podosome formation without effect on extracellular signal
      regulated kinase 1/2 activation. Additionally, we provide evidence that GIT1
      knockout VSMC have markedly fewer podosomes on PDBU treatment compared with wild
      type VSMC. These data show that GIT1 is a key regulator of podosome formation in
      VSMC. CONCLUSIONS: In conclusion, our data suggest that GIT1-Y392 phosphorylation
      is critical for PDBU-induced podosome formation by regulating PLCgamma
      activation. We propose that specific signaling modules are assembled in a GIT1
      phosphotyrosine-dependent manner as exemplified by PLCgamma activation versus
      extracellular signal-regulated kinase 1/2 activation.

PMID- 20689072
TI  - Epigenome mapping in normal and disease States.
AB  - Epigenomes are comprised, in part, of all genome-wide chromatin modifications,
      including DNA methylation and histone modifications. Unlike the genome,
      epigenomes are dynamic during development and differentiation to establish and
      maintain cell type-specific gene expression states that underlie cellular
      identity and function. Chromatin modifications are particularly labile, providing
      a mechanism for organisms to respond and adapt to environmental cues. Results
      from studies in animal models clearly demonstrate that epigenomic variability
      leads to phenotypic variability, including susceptibility to disease that is not
      recognized at the DNA sequence level. Thus, capturing epigenomic information is
      invaluable for comprehensively understanding development, differentiation, and
      disease. Herein, we provide a brief overview of epigenetic processes, how they
      are relevant to human health, and review studies using technologies that enable
      epigenome mapping. We conclude by describing feasible applications of epigenome
      mapping, focusing on epigenome-wide association studies (eGWAS), which have the
      potential to revolutionize current studies of human diseases and will likely
      promote the discovery of novel diagnostic, preventative, and treatment
      strategies.

PMID- 20689074
TI  - Inhibition of p38 mitogen-activated protein kinase reduces inflammation after
      coronary vascular injury in humans.
AB  - OBJECTIVE: To evaluate whether a p38alpha/beta mitogen-activated protein kinase
      inhibitor, SB-681323, would limit the elevation of an inflammatory marker, high
      sensitivity C-reactive protein (hsCRP), after a percutaneous coronary
      intervention (PCI). METHODS AND RESULTS: Coronary artery stents provide benefit
      by maintaining lumen patency but may incur vascular trauma and inflammation,
      leading to myocardial damage. A key mediator for such stress signaling is p38
      mitogen-activated protein kinase. Patients with angiographically documented
      coronary artery disease receiving stable statin therapy and about to undergo PCI
      were randomly selected to receive SB-681323, 7.5 mg (n=46), or placebo (n=46)
      daily for 28 days, starting 3 days before PCI. On day 3, before PCI, hsCRP was
      decreased in the SB-681323 group relative to the placebo group (29% lower;
      P=0.02). After PCI, there was a statistically significant attenuation in the
      increase in hsCRP in the SB-681323 group relative to the placebo group (37% lower
      on day 5 [P=0.04]; and 40% lower on day 28 [P=0.003]). There were no adverse
      safety signals after 28 days of treatment with SB-681323. CONCLUSIONS: In the
      setting of statin therapy, SB-681323 significantly attenuated the post-PCI
      inflammatory response, as measured by hsCRP. This inflammatory dampening
      implicates p38 mitogen-activated protein kinase in the poststent response,
      potentially defining an avenue to limit poststent restenosis.

PMID- 20689075
TI  - Combination of injectable multiple growth factor-releasing scaffolds and cell
      therapy as an advanced modality to enhance tissue neovascularization.
AB  - OBJECTIVE: Vasculogenic progenitor cell therapy for ischemic diseases bears great
      potential but still requires further optimization for justifying its clinical
      application. Here, we investigated the effects of in vivo tissue engineering by
      combining vasculogenic progenitors with injectable scaffolds releasing controlled
      amounts of proangiogenic growth factors. METHODS AND RESULTS: We produced
      biodegradable, injectable polylactic coglycolic acid-based scaffolds releasing
      single factors or combinations of vascular endothelial growth factor, hepatocyte
      growth factor, and angiopoietin-1. Dual and triple combinations of scaffold
      released growth factors were superior to single release. In murine hindlimb
      ischemia models, scaffolds releasing dual (vascular endothelial growth factor and
      hepatocyte growth factor) or triple combinations improved effects of cord blood
      derived vasculogenic progenitors. Increased migration, homing, and incorporation
      of vasculogenic progenitors into the vasculature augmented capillary density,
      translating into improved blood perfusion. Most importantly, scaffold-released
      triple combinations including the vessel stabilizer angiopoietin-1 enhanced the
      number of perivascular smooth muscle actin(+) vascular smooth muscle cells,
      indicating more efficient vessel stabilization. CONCLUSIONS: Vasculogenic
      progenitor cell therapy is significantly enhanced by in vivo tissue engineering
      providing a proangiogenic and provasculogenic growth factor-enriched
      microenvironment. Therefore, combined use of scaffold-released growth factors and
      cell therapy improves neovascularization in ischemic diseases and may translate
      into more pronounced clinical effects.

PMID- 20689076
TI  - Aging induces endothelial dysfunction while sparing arterial thrombosis.
AB  - OBJECTIVE: To assess the effects of aging on arterial thrombus formation by
      comparing 2-year-old with 11-week-old C57Bl6 mice. METHODS AND RESULTS: Aging is
      a major risk factor for cardiovascular disease. In humans, assessing the direct
      effects of aging on vascular homeostasis is difficult because it occurs in the
      presence of other risk factors. Arterial thrombosis is the critical event in
      cardiovascular diseases; however, it is not known whether aging per se promotes
      its occurrence. Mice represent an interesting system to address this issue
      because they age without spontaneously developing other risk factors. Organ
      chamber experiments confirmed the advanced level of aging of old mice. As
      previously shown, old mice exhibited endothelial dysfunction; however, arterial
      thrombosis induced by photochemical injury was unchanged. Arterial tissue factor
      expression and activity; expressions of tissue factor pathway inhibitor,
      thrombomodulin, and plasminogen activator inhibitor 1; prothrombin time; partial
      thromboplastin time; thrombin-antithrombin complex; and platelet activation were
      comparable in both groups. CONCLUSIONS: Although these results cannot be directly
      extrapolated to humans, this study contributes novel important information on the
      direct effect of aging on arterial thrombosis and underscores the importance of
      controlling modifiable risk factors in aged individuals.

PMID- 20689077
TI  - Endogenous KLF4 expression in human fetal endothelial cells allows for
      reprogramming to pluripotency with just OCT3/4 and SOX2--brief report.
AB  - OBJECTIVE: The introduction of 4 transcription factors-c-MYC, OCT3/4, SOX2, and
      KLF4--can reprogram somatic cells back to pluripotency. However, some of the
      factors used are oncogenic, making therapeutic application unfeasible. Although
      the use of adult stem cells expressing high endogenous levels of some of these
      factors allows for reprogramming with fewer exogenous genes, such cells are rare
      and may have accumulated genetic mutations. Our goal was to reprogram human
      somatic cells without oncogenic factors. We found that high endogenous expression
      of KLF4 in human umbilical vein endothelial cells (HUVECs) allows for generation
      of induced pluripotent stem cells (iPSCs) with just 2 nononcogenic factors,
      OCT3/4 and SOX2. METHODS AND RESULTS: HUVECs were infected with lentivirus
      containing OCT4 and SOX2 for generation of iPSCs. These 2-factor HUVEC iPSCs were
      morphologically similar to embryonic stem cells, express endogenous pluripotency
      markers postreprogramming, and can differentiate toward lineages of all 3 germ
      layers both in vitro and in vivo. CONCLUSIONS: iPSCs can be generated from HUVECs
      with only 2 nononcogenic factors. The use of fetal cells for reprogramming
      without oncogenic factors may provide an efficient in vitro model for human iPSC
      research, as well as a novel source for possible therapeutic use.

PMID- 20689079
TI  - Interleukin-18 as a predictor of future events in patients with acute coronary
      syndromes.
AB  - OBJECTIVE: The aim of this study was to assess the short- and long-term
      prognostic significance of interleukin-18 (IL-18) levels in patients with acute
      coronary syndromes (ACS). METHODS AND RESULTS: In patients hospitalized with ACS
      (median age, 66 years; 30% females), we evaluated associations of serum IL-18
      levels from day 1 (n=1261) with the short- (<3 months) and long-term (median, 7.6
      years) risk of death, development of congestive heart failure (CHF), and
      myocardial infarction (MI). IL-18 was not significantly associated with short
      term mortality. In the long term, IL-18 levels were significantly related to all
      cause mortality, even after adjustment for clinical confounders (hazard ratio
      [HR], 1.19; 95% confidence interval, 1.07 to 1.33; P=0.002). Long-term,
      cardiovascular mortality was univariately related to IL-18, and the adjusted
      relation between noncardiovascular mortality and IL-18 was highly significant
      (HR, 1.36; 95% confidence interval, 1.11 to 1.67; P=0.003). IL-18 independently
      predicted CHF, MI, and cardiovascular death/CHF/MI in both the short and long
      term. Measurements from day 1 of ACS and 3 months after ACS had a similar power
      to predict late outcome. CONCLUSIONS: The addition of the measurement of IL-18 to
      clinical variables improved the prediction of risk of all-cause and
      noncardiovascular mortality. The association between IL-18 and noncardiovascular
      mortality is intriguing and warrants further study.

PMID- 20689078
TI  - Pioglitazone suppresses inflammation in vivo in murine carotid atherosclerosis:
      novel detection by dual-target fluorescence molecular imaging.
AB  - OBJECTIVE: To investigate the effects of pioglitazone (PIO), a peroxisome
      proliferator-activated receptor gamma agonist, on plaque matrix metalloproteinase
      (MMP) and macrophage (Mac) responses in vivo in a molecular imaging study.
      METHODS AND RESULTS: In vitro, PIO suppressed MMP-9 protein expression in murine
      peritoneal Macs (P<0.05). To assess PIO's effects on plaque inflammation,
      nondiabetic apolipoprotein E(-/-) mice receiving a high-cholesterol diet (HCD)
      were administered an MMP-activatable fluorescence imaging agent and a spectrally
      distinct Mac-avid fluorescent nanoparticle. After 24 hours, mice underwent
      survival dual-target intravital fluorescence microscopy of carotid arterial
      plaques. These mice were then randomized to HCD or HCD plus 0.012% PIO for 8
      weeks, followed by a second intravital fluorescence microscopy study of the same
      carotid plaque. In the HCD group, in vivo MMP and Mac target-to-background ratios
      increased similarly (P<0.01 versus baseline). In contrast, PIO reduced MMP and
      Mac target-to-background ratios (P<0.01) versus HCD. Changes in MMP and Mac
      signals correlated strongly (r >=0.75). Microscopy demonstrated MMP and Mac
      reductions in PIO-treated mice and a PIO-modulated increase in plaque collagen.
      CONCLUSIONS: Serial optical molecular imaging demonstrates that plaque MMP and
      Mac activity in vivo intensify with hypercholesterolemia and are reduced by PIO
      therapy.

PMID- 20689080
TI  - Stroke thrombolysis: having more time translates into delayed therapy: data from
      the Austrian Stroke Unit Registry.
AB  - BACKGROUND AND PURPOSE: Efficacy of intravenous thrombolysis in acute ischemic
      stroke declines with increasing time to treatment initiation. Previous small
      scale studies suggested that the earlier patients arrive, the longer it takes to
      administer recombinant tissue plasminogen activator. METHODS: Of 32 529 patients
      with stroke prospectively enrolled in the Austrian Stroke Unit Registry (2004 to
      2009), 3287 received intravenous thrombolysis and 2663 of them were eligible for
      the current analysis. RESULTS: Median (interquartile range) onset-to-door and
      door-to-needle times were 70 (50 to 100) and 50 (35 to 70) minutes. Of note, both
      time intervals were inversely correlated with each other. After adjustment for
      multiple stroke characteristics, the door-to-needle time of patients arriving in
      the hospital within the first hour after stroke onset was 6.9 minutes (P<0.001)
      and 13.9 minutes (P<0.001) longer than those for patients arriving between 61 to
      120 and 121 to 180 minutes. Findings were consistent in subgroups. CONCLUSIONS:
      Early hospital arrival translates into a significant delay in the application of
      intravenous thrombolysis among patients with acute stroke. This finding calls for
      concerted measures to ensure that all patients with stroke are treated with the
      same urgency irrespective of the time available.

PMID- 20689081
TI  - Lack of association between pretreatment neurology consultation and subsequent
      protocol deviation in tissue plasminogen activator-treated patients with stroke.
AB  - BACKGROUND AND PURPOSE: We evaluated the hypothesis that consultation with
      neurology would be associated with fewer protocol deviations in tissue
      plasminogen activator-treated patients with stroke. METHODS: A retrospective
      analysis of consecutive tissue plasminogen activator-treated patients with acute
      patients was performed. Using chi(2) tests, the proportion of patients with a
      protocol deviation was calculated and compared between those with evidence of a
      neurology consultation and those without. Logistic regression was then used to
      determine the OR for protocol deviation at the same time as controlling for
      clinical presentation covariates. RESULTS: Two hundred seventy-three subjects
      were included. Protocol deviation rates did not significantly differ between
      those with (44%) and those without (41%) a consultation. The adjusted OR for
      deviation comparing any consultation versus nonconsultation was 1.25 (95% CI:
      0.58 to 2.68). There was no statistically significant difference between
      symptomatic intracranial hemorrhage and in-hospital mortality rates between the
      groups. The proportion of patients with pretreatment deviations not related to
      timing was low in both the consultation (9.7%) and nonconsultation groups (8.1%).
      CONCLUSIONS: Neurological consultation was not found to be associated with
      decreased protocol deviations in this cohort, although the high proportion of
      deviations with and without consultation suggests that quality improvement is
      needed. Most observed pretreatment deviations were attributable to timing. As
      acute stroke care becomes more efficient and additional methods in reducing door
      to-treatment times are sought, models in which emergency physicians direct the
      initial phase of treatment may merit further consideration.

PMID- 20689082
TI  - Associations between peripheral artery disease and ischemic stroke: implications
      for primary and secondary prevention.
AB  - BACKGROUND AND PURPOSE: Although peripheral artery disease (PAD) has a
      particularly poor prognosis compared with vascular disease in other territories,
      little attention is paid to its epidemiology, treatment, and prevention. Despite
      the high prevalence of PAD in patients with stroke, and of stroke in patients
      with PAD, PAD is omitted from all guidelines for treatment, prevention, and
      rehabilitation of stroke, although coronary artery disease risk is considered.
      Therefore, routine PAD screening is seldom undertaken and so disease is probably
      often missed. Summary of Review- This review evaluates epidemiology of PAD in
      patients with stroke and of stroke in patients with PAD. The role of the ankle
      brachial pressure index; imaging and novel markers in risk prediction of PAD in
      patients with stroke; and treatment and prevention of PAD are reviewed.
      CONCLUSIONS: In both primary and secondary prevention settings, PAD indicates a
      high risk of future events. Data on which additional preventive measures are
      beneficial in this patient group are lacking, but the presence of PAD does have
      implications for current management in both primary and secondary prevention of
      stroke.

PMID- 20689083
TI  - Ischemic stroke subtypes in a Japanese population: Takashima Stroke Registry,
      1988-2004.
AB  - BACKGROUND AND PURPOSE: Population-based information on the epidemiology of
      ischemic stroke (IS) subtypes is scant. In this study, we characterized IS
      subtypes in terms of incidence, time trend, and risk factor profiles in a
      community-based population. METHODS: We obtained data from the Takashima Stroke
      Registry on approximately 55 000 residents of Takashima County in central Japan
      and calculated age-adjusted stroke incidence rates for different IS subtypes. We
      determined the incidence time trend by calculating the average annual change
      across years and also compared risk factors between subtypes. RESULTS: There were
      1389 first-ever ischemic strokes registered during 1988 to 2004. Lacunar
      infarction was the most frequent etiology (54.1%) followed by cardioembolic
      infarction (22.9%). Age-adjusted incidence rates for different IS subtypes were
      lacunar, 77.1; cardioembolic, 31.5; and nonlacunar, 29.7/10(5) person-years. The
      average annual change was not significant for the IS subtypes except for
      nonlacunar infarction, which showed a decreasing trend. Risk factor analysis
      showed that patients with lacunar infarctions were younger and less likely to
      have a history of transient ischemic attack or a drinking habit than patients
      with nonlacunar infarctions. CONCLUSIONS: Lacunar infarct was the most common IS
      subtype in our population. We found no significant change in the incidence of
      subtypes during the study, except a decrease in nonlacunar infarction.

PMID- 20689084
TI  - MRI markers of small vessel disease in lobar and deep hemispheric intracerebral
      hemorrhage.
AB  - BACKGROUND AND PURPOSE: MRI evidence of small vessel disease is common in
      intracerebral hemorrhage (ICH). We hypothesized that ICH caused by cerebral
      amyloid angiopathy (CAA) or hypertensive vasculopathy would have different
      distributions of MRI T2 white matter hyperintensity (WMH) and microbleeds.
      METHODS: Data were analyzed from 133 consecutive patients with primary
      supratentorial ICH and adequate MRI sequences. CAA was diagnosed using the Boston
      criteria. WMH segmentation was performed using a validated semiautomated method.
      WMH and microbleeds were compared according to site of symptomatic hematoma
      origin (lobar versus deep) or by pattern of hemorrhages, including both hematomas
      and microbleeds, on MRI gradient recalled echo sequence (grouped as lobar only
      probable CAA, lobar only-possible CAA, deep hemispheric only, or mixed lobar and
      deep hemorrhages). RESULTS: Patients with lobar and deep hemispheric hematoma had
      similar median normalized WMH volumes (19.5 cm versus 19.9 cm(3), P=0.74) and
      prevalence of >or=1 microbleed (54% versus 52%, P=0.99). The supratentorial WMH
      distribution was similar according to hemorrhage location category; however, the
      prevalence of brain stem T2 hyperintensity was lower in lobar hematoma versus
      deep hematoma (54% versus 70%, P=0.004). Mixed ICH was common (23%). Patients
      with mixed ICH had large normalized WMH volumes and a posterior distribution of
      cortical hemorrhages similar to that seen in CAA. CONCLUSIONS: WMH distribution
      is largely similar between CAA-related and non-CAA-related ICH. Mixed lobar and
      deep hemorrhages are seen on MRI gradient recalled echo sequence in up to one
      fourth of patients; in these patients, both hypertension and CAA may be
      contributing to the burden of WMH.

PMID- 20689085
TI  - Diagnostic threshold values of cerebral perfusion measured with computed
      tomography for delayed cerebral ischemia after aneurysmal subarachnoid
      hemorrhage.
AB  - BACKGROUND AND PURPOSE: Early diagnosis of delayed cerebral ischemia (DCI) after
      aneurysmal subarachnoid hemorrhage is critical but difficult. We analyzed
      diagnostic threshold values of CT perfusion for use in detection of DCI in
      patients with subarachnoid hemorrhage. METHODS: We prospectively enrolled
      patients with subarachnoid hemorrhage with CT perfusion on admission and at time
      of clinical deterioration or after 1 week if no deterioration occurred. The gold
      standard was the clinical diagnosis of DCI based on all clinical, laboratory, and
      imaging data except CT perfusion. Patients with failed imaging (n=6) and other
      causes of deterioration (n=45) were excluded for the current study. We measured
      CT perfusion values, including cerebral blood volume, blood flow, mean transit
      time (MTT), and time to peak in predefined regions of interest and then compared
      absolute perfusion and perfusion asymmetry for patients with and without DCI.
      Diagnostic threshold values for DCI were evaluated and sensitivity and
      specificity calculated for optimal thresholds. RESULTS: Of 85 eligible patients
      with subarachnoid hemorrhage, 50 had DCI; 35 patients with no clinical
      deterioration comprised the reference group. Cerebral blood flow was
      significantly lower, MTT higher, and perfusion asymmetry larger in patients with
      DCI. We found that largest absolute MTT and the MTT difference between
      hemispheres were good diagnostic tests. Diagnostic threshold values with optimal
      sensitivity and specificity were an MTT of 5.9 seconds and an MTT difference of
      1.1 second. CONCLUSIONS: Thresholds for absolute MTT values and between
      hemisphere MTT differences on CT perfusion can distinguish between patients with
      delayed cerebral ischemia and clinically stable patients.

PMID- 20689086
TI  - Stroke Incidence and Survival in Ludwigshafen am Rhein, Germany: the Ludwigshafen
      Stroke Study (LuSSt).
AB  - BACKGROUND AND PURPOSE: Considerable locoregional differences in stroke incidence
      exist even within countries. Based on data from a statewide stroke care quality
      monitoring project, we hypothesized a high stroke incidence mainly among younger
      age groups in the industrial city of Ludwigshafen am Rhein, Germany. To test this
      hypothesis and to provide data on stroke incidence and case-fatality rates, a
      population-based stroke register was initiated. METHODS: The Ludwigshafen Stroke
      Study is a prospective ongoing population-based stroke register among the 167 906
      inhabitants of Ludwigshafen am Rhein. Starting on January 1, 2006, standard
      definitions and multiple overlapping methods of case ascertainment were used to
      identify all patients with incident stroke or transient ischemic attack. RESULTS:
      In 2006 and 2007, 1231 cases with stroke or transient ischemic attack including
      725 patients with first-ever stroke were identified. The crude annual incidence
      rate per 1000 for first-ever stroke was 2.16 (95% CI 2.10 to 2.32). After age
      adjustment to the European population, incidence for first-ever stroke was 1.46
      (95% CI 1.35 to 1.57; men: 1.63; 95% CI 1.46 to 1.81; women: 1.29; 95% CI 1.15 to
      1.43). Crude annual incidence rates per 1000 were 1.86 for ischemic stroke, 0.19
      for intracerebral hemorrhage, 0.05 for subarachnoid hemorrhage, and 0.05 for
      undetermined stroke. Case-fatality rates for first-ever stroke were 13.6%, 16.4%,
      and 23.2% at Days 28, 90, and 365, respectively. CONCLUSIONS: High crude
      incidence rates in our study reflect the rising burden of stroke in our aging
      population. Age-adjusted incidence rates were somewhat higher than those reported
      by recent studies from Western Europe, mainly due to higher incidence in subjects
      <65 years.

PMID- 20689087
TI  - Rapid in vivo whole body composition of rats using cone beam MUCT.
AB  - Precise, noninvasive analysis and quantification of in vivo body composition is
      essential for research involving longitudinal, small-animal disease models. We
      investigated the feasibility and precision of a rapid, flat-panel MUCT scanner to
      report whole body adipose tissue volume (ATV), lean tissue volume (LTV), skeletal
      tissue volume (STV), and bone mineral content (BMC) in 25 postmortem female and
      52 live male Sprague-Dawley rats. MUCT images, acquired in three 90-mm segments
      and reconstructed with 308 MUm of isotropic voxel spacing, formed contiguous
      image volumes of each entire rat specimen. Three signal-intensity thresholds
      (determined to be -186, 5, and 155 HU) were used to classify each voxel as
      adipose, lean, or skeletal tissue, respectively. Tissue masses from the volume
      fractions of ATV, LTV, and STV were calculated from assumed tissue densities of
      0.95, 1.05, and 1.92 g/cm(-3), respectively. A CT-derived total mass was
      calculated for each rat and compared with the gravimetrically measured mass,
      which differed on average for the postmortem female and the live male group by
      2.5 and 1.1%, respectively. To evaluate the accuracy of the CT-derived body
      composition technique, following the live male study excised muscle tissue in the
      lower right leg of all rats in group B were compared with the image-derived LT
      measurement of the same regional compartment and found to differ on average by
      2.2%. Through repeated CT measurements of postmortem specimens, the whole body
      ATV, LTV, STV, and BMC measurement analysis gave a precision value of +/-0.6,
      1.9, 1.7, and 0.5% of the average value, respectively.

PMID- 20689088
TI  - Hypoxia-induced intrapulmonary arteriovenous shunting at rest in healthy humans.
AB  - Intrapulmonary arteriovenous (IPAV) shunting has been shown to occur at rest in
      some subjects breathing a hypoxic gas mixture [fraction of inspired oxygen
      (FI(O(2))) = 0.12] for brief periods of time. In the present study we set out to
      determine if IPAV shunting could be induced at rest in all subjects exposed to
      hypoxia for 30 min. Twelve subjects (6 women) breathed four levels of hypoxia
      (FI(O(2)) = 0.16, 0.14, 0.12, and 0.10) for 30 min each in either an ascending or
      descending order with a 15-min normoxic break between bouts. Saline contrast
      echocardiography was used to detect IPAV shunt and a shunt score (0-5) was
      assigned based on contrast in the left ventricle with a shunt score >= 2
      considered significant. Pulmonary artery systolic pressure (PASP) was determined
      using Doppler ultrasound. The total number of subjects demonstrating shunt scores
      >= 2 for FI(O(2)) = 0.16, 0.14, 0.12, and 0.10 was 1/12, 7/12, 9/12, and 12/12,
      respectively. Shunt scores were variable between subjects but significantly
      greater than normoxia for FI(O(2)) = 0.12 and 0.10. Shunt scores correlated with
      peripheral measurements of arterial oxygen saturation (SpO(2)) (r(w) = -0.67) and
      PASP (r(w) = 0.44), despite an increased shunt score but no increase in PASP
      while breathing an FI(O(2)) = 0.12. It is unknown how hypoxia induces the opening
      of IPAV shunts, but these vessels may be controlled via similar mechanisms as
      systemic vessels that vasodilate in response to hypoxia. Despite intersubject
      variability our results indicate significant IPAV shunting occurs at rest in all
      subjects breathing an FI(O(2)) = 0.10 for 30 min.

PMID- 20689089
TI  - The two-hour marathon: who and when?
AB  - Whoever breaks 2 h will likely have outstanding running economy and small body
      size along with exposure to high altitude and significant physical activity early
      in life. However, neither of these factors nor any specific suite of genotypes
      appear to be obligatory for a time this fast. Current trends suggest that an East
      African will be the first to break 2 h. However periods of regional dominance in
      distance running are not unique to the East Africans: athletes from Finland,
      Eastern Europe, Australia, and New Zealand have all had extended periods of
      success at a range of distances. From a physiological perspective, more
      information is clearly needed on the relationship between VO(2max) and running
      economy and the influence of running economy and body size on thermoregulation
      and fuel use.

PMID- 20689090
TI  - Mechanisms of aerobic performance impairment with heat stress and dehydration.
AB  - Environmental heat stress can challenge the limits of human cardiovascular and
      temperature regulation, body fluid balance, and thus aerobic performance. This
      minireview proposes that the cardiovascular adjustments accompanying high skin
      temperatures (T(sk)), alone or in combination with high core body temperatures
      (T(c)), provide a primary explanation for impaired aerobic exercise performance
      in warm-hot environments. The independent (T(sk)) and combined (T(sk) + T(c))
      effects of hyperthermia reduce maximal oxygen uptake (Vo(2max)), which leads to
      higher relative exercise intensity and an exponential decline in aerobic
      performance at any given exercise workload. Greater relative exercise intensity
      increases cardiovascular strain, which is a prominent mediator of rated perceived
      exertion. As a consequence, incremental or constant-rate exercise is more
      difficult to sustain (earlier fatigue) or requires a slowing of self-paced
      exercise to achieve a similar sensation of effort. It is proposed that high T(sk)
      and T(c) impair aerobic performance in tandem primarily through elevated
      cardiovascular strain, rather than a deterioration in central nervous system
      (CNS) function or skeletal muscle metabolism. Evaporative sweating is the
      principal means of heat loss in warm-hot environments where sweat losses
      frequently exceed fluid intakes. When dehydration exceeds 3% of total body water
      (2% of body mass) then aerobic performance is consistently impaired independent
      and additive to heat stress. Dehydration augments hyperthermia and plasma volume
      reductions, which combine to accentuate cardiovascular strain and reduce
      Vo(2max). Importantly, the negative performance consequences of dehydration
      worsen as T(sk) increases.

PMID- 20689091
TI  - Early right ventriculo-arterial uncoupling in borderline pulmonary hypertension
      on experimental heart failure.
AB  - Pulmonary hypertension on heart failure (HF) limits exercise capacity and
      survival probably because of associated right ventricular (RV) failure. This
      study investigated the mechanisms of RV function adaptation to early pulmonary
      hypertension in experimental HF. Seven weeks of rapid ventricular pacing in six
      dogs induced a HF characterized by cardiomegaly and decreased left ventricular
      ejection fraction. Compared with eight control dogs, pulmonary hypertension was
      borderline, with a mean pulmonary artery pressure increased to only 23 +/- 2
      (means +/- SE) mmHg. However, the pulmonary vascular impedance spectrum was
      globally shifted to higher pressures, with an increase in 0 Hz impedance
      (resistance) to 662 +/- 69 vs. 455 +/- 41 dynes.cm(-5).m(2) in controls (P <
      0.01) and in characteristic impedance to 183 +/- 20 vs. 104 +/- 7 dynes.cm(
      5).m(2) in controls (P < 0.01). There was no change in RV end-systolic elastance
      (Ees), but arterial elastance (Ea) was increased to 1.8 +/- 0.3 vs. 0.9 +/- 0.1
      mmHg/ml in controls so that RV-arterial coupling defined by the Ees-to-Ea ratio
      (Ees/Ea) was decreased to 0.8 +/- 0.1 vs. 1.5 +/- 0.1 in controls (P < 0.01).
      Inhaled nitric oxide, 40 ppm or 5 MUg.kg(-1).min(-1) nitroprusside i.v., did not
      affect Ees/Ea. Fifty milligrams (i.v.) of milrinone increased Ees/Ea to 1.6 +/-
      0.2 by an isolated increase in Ees. We conclude that overpacing-induced HF is
      accompanied by a borderline pulmonary hypertension but profound RV-arterial
      uncoupling explained by the failure of RV systolic function to adapt combined
      effects of increased pulmonary arterial resistance and elastance.

PMID- 20689092
TI  - Control of breathing during dynamic exercise by thin fiber muscle afferents.

PMID- 20689093
TI  - Muscle dependency of corticomuscular coherence in upper and lower limb muscles
      and training-related alterations in ballet dancers and weightlifters.
AB  - It has been well documented that the 15- to 35-Hz oscillatory activity of the
      sensorimotor cortex shows coherence with the muscle activity during weak to
      moderate steady contraction. To investigate the muscle dependency of the
      corticomuscular coherence and its training-related alterations, we quantified the
      coherence between electroencephalogram (EEG) from the sensorimotor cortex and
      rectified electromyogram (EMG) from five upper limb (first dorsal interosseous,
      flexor carpi radialis, extensor carpi radialis, biceps brachii, triceps brachii)
      and four lower limb muscles (soleus, tibialis anterior, biceps femoris, rectus
      femoris), while maintaining a constant force level at 30% of maximal voluntary
      contraction of each muscle, in 24 untrained, 12 skill-trained (ballet dancers),
      and 10 strength-trained (weightlifters) individuals. Data from untrained subjects
      demonstrated the muscle dependency of corticomuscular coherence. The magnitude of
      the EEG-EMG coherence was significantly greater in the distally located lower
      limb muscles, such as the soleus and tibialis anterior, than in the upper or
      other lower limb muscles in untrained subjects (P < 0.05). These results imply
      that oscillatory coupling between the sensorimotor cortex and spinal motoneurons
      during steady contraction differs among muscles, according to the functional role
      of each muscle. In addition, the ballet dancers and weightlifters showed smaller
      EEG-EMG coherences than the untrained subjects, especially in the lower limb
      muscles (P < 0.05). These results indicate that oscillatory interaction between
      the sensorimotor cortex and spinal motoneurons can be changed by long-term
      specialized use of the muscles and that this neural adaptation may lead to finer
      control of muscle force during steady contraction.

PMID- 20689094
TI  - The relationship between cardiac output and dynamic cerebral autoregulation in
      humans.
AB  - Cerebral autoregulation adjusts cerebrovascular resistance in the face of
      changing perfusion pressures to maintain relatively constant flow. Results from
      several studies suggest that cardiac output may also play a role. We tested the
      hypothesis that cerebral blood flow would autoregulate independent of changes in
      cardiac output. Transient systemic hypotension was induced by thigh-cuff
      deflation in 19 healthy volunteers (7 women) in both supine and seated positions.
      Mean arterial pressure (Finapres), cerebral blood flow (transcranial Doppler) in
      the anterior (ACA) and middle cerebral artery (MCA), beat-by-beat cardiac output
      (echocardiography), and end-tidal Pco(2) were measured. Autoregulation was
      assessed using the autoregulatory index (ARI) defined by Tiecks et al. (Tiecks
      FP, Lam AM, Aaslid R, Newell DW. Stroke 26: 1014-1019, 1995). Cerebral
      autoregulation was better in the supine position in both the ACA [supine ARI: 5.0
      +/- 0.21 (mean +/- SE), seated ARI: 3.9 +/- 0.4, P = 0.01] and MCA (supine ARI:
      5.0 +/- 0.2, seated ARI: 3.8 +/- 0.3, P = 0.004). In contrast, cardiac output
      responses were not different between positions and did not correlate with
      cerebral blood flow ARIs. In addition, women had better autoregulation in the ACA
      (P = 0.046), but not the MCA, despite having the same cardiac output response.
      These data demonstrate cardiac output does not appear to affect the dynamic
      cerebral autoregulatory response to sudden hypotension in healthy controls,
      regardless of posture. These results also highlight the importance of considering
      sex when studying cerebral autoregulation.

PMID- 20689095
TI  - Protein and carbohydrate supplementation during 5-day aerobic training enhanced
      plasma volume expansion and thermoregulatory adaptation in young men.
AB  - We examined whether protein and carbohydrate (CHO) supplementation during 5-day
      training enhanced plasma volume (PV) expansion and thermoregulatory and
      cardiovascular adaptations in young men. Eighteen men [age 23 +/- 4 (SD) yr] were
      divided into two groups according to supplements: placebo (CNT: 0.93 kcal/kg,
      0.00 g protein/kg, n = 9) and protein and CHO (Pro-CHO: 3.6 kcal/kg, 0.36
      protein/kg, n = 9). Subjects in both groups performed a cycling exercise at 70%
      peak oxygen consumption rate (VO2peak), 30 min/day, for 5 consecutive days at 30
      degrees C ambient temperature and 50% relative humidity and took either a placebo
      or Pro-CHO within 10 min after exercise for each day. Before and after training,
      PV at rest, heart rate (HR), and esophageal temperature (T(es)) during 30-min
      exercise at 65% of pretraining VO2peak in the same condition as training were
      determined. Also, the sensitivity of the chest sweat rate (DeltaSR/DeltaT(es))
      and forearm vascular conductance (DeltaFVC/DeltaT(es)) in response to increased
      T(es) were determined. After training, PV and cardiac stroke volume (SV) at rest
      increased in both groups (P < 0.001) but the increases were twofold higher in Pro
      CHO than CNT (P = 0.007 and P = 0.078, respectively). The increases in HR from 5
      to 30 min and T(es) from 0 to 30 min of exercise were attenuated after training
      in both groups with greater attenuation in Pro-CHO than CNT (P = 0.002 and P =
      0.072, respectively). DeltaSR/DeltaT(es) increased in CNT (P = 0.052) and Pro-CHO
      (P < 0.001) and the increases were higher in Pro-CHO than CNT (P = 0.018).
      DeltaFVC/DeltaT(es) increased in Pro-CHO (P < 0.001), whereas not in CNT (P =
      0.16). Thus protein-CHO supplementation during 5-day training enhanced PV
      expansion and thermoregulatory adaptation and, thereby, the reduction in heat and
      cardiovascular strain in young men.

PMID- 20689096
TI  - Derivation of a finite-element model of lingual deformation during swallowing
      from the mechanics of mesoscale myofiber tracts obtained by MRI.
AB  - To demonstrate the relationship between lingual myoarchitecture and mechanics
      during swallowing, we performed a finite-element (FE) simulation of lingual
      deformation employing mesh aligned with the vector coordinates of myofiber tracts
      obtained by diffusion tensor imaging with tractography in humans. Material
      properties of individual elements were depicted in terms of Hill's three
      component phenomenological model, assuming that the FE mesh was composed of
      anisotropic muscle and isotropic connective tissue. Moreover, the mechanical
      model accounted for elastic constraints by passive and active elements from the
      superior and inferior directions and the effect of out-of-plane muscles and
      connective tissue. Passive bolus effects were negligible. Myofiber tract
      activation was simulated over 500 ms in 1-ms steps following lingual tip
      association with the hard palate and incorporated specifically the accommodative
      and propulsive phases of the swallow. Examining the displacement field, active
      and passive muscle stress, elemental stretch, and strain rate relative to changes
      of global shape, we demonstrate that lingual reconfiguration during these swallow
      phases is characterized by (in sequence) the following: 1) lingual tip elevation
      and shortening in the anterior-posterior direction; 2) inferior displacement
      related to hyoglossus contraction at its inferior-most position; and 3) dominant
      clockwise rotation related to regional contraction of the genioglossus and
      contraction of the hyoglossus following anterior displacement. These simulations
      demonstrate that lingual deformation during the indicated phases of swallowing
      requires temporally patterned activation of intrinsic and extrinsic muscles and
      delineate a method to ascertain the mechanics of normal and pathological
      swallowing.

PMID- 20689098
TI  - Extracellular ubiquitin: immune modulator and endogenous opponent of damage
      associated molecular pattern molecules.
AB  - Ubiquitin is a post-translational protein modifier and plays essential roles in
      all aspects of biology. Although the discovery of ubiquitin introduced this
      highly conserved protein as a molecule with extracellular actions, the
      identification of ubiquitin as the ATP-dependent proteolysis factor 1 has focused
      subsequent research on its important intracellular functions. Little attention
      has since been paid to its role outside of the cell. During recent years,
      multiple observations suggest that extracellular ubiquitin can modulate immune
      responses and that exogenous ubiquitin has therapeutic potential to attenuate
      exuberant inflammation and organ injury. These observations have not been
      integrated into a comprehensive assessment of its possible role as an endogenous
      immune modulator. This review recapitulates the current knowledge about
      extracellular ubiquitin and discusses an emerging facet of its role in biology
      during infectious and noninfectious inflammation. The synopsis of these data
      along with the recent identification of ubiquitin as a CXCR4 agonist suggest that
      extracellular ubiquitin may have pleiotropic roles in the immune system and
      functions as an endogenous opponent of DAMPs. Functions of extracellular
      ubiquitin could constitute an evolutionary conserved control mechanism aimed to
      balance the immune response and prevent exuberant inflammation. Further
      characterization of its mechanism of action and cellular signaling pathways is
      expected to provide novel insights into the regulation of the innate immune
      response and opportunities for therapeutic interventions.

PMID- 20689097
TI  - Asymmetric superoxide release inside and outside the mitochondria in skeletal
      muscle under conditions of aging and disuse.
AB  - Superoxide released from mitochondria forms reactive oxygen species that can
      cause severe oxidative damage and have been associated with aging- and disuse
      induced muscle dysfunction. Superoxide is released to both the exterior and the
      matrix of mitochondria, where oxidative damage is not necessarily the same. This
      complicates determining the role of mitochondrial superoxide in eliciting
      oxidative stress in skeletal muscle. A newly developed capillary electrophoretic
      method analyzes hydroxytriphenylphosphonium ethidium, a superoxide-specific
      product of triphenylphosphonium hydroethidine, released to outside the
      mitochondria (supernatant) and retained in the matrix (pellet). In this study, we
      investigated the mitochondrial superoxide production of soleus (type I) and
      semimembranosus (type II) muscles of Fischer 344 rats affected by aging (13 vs.
      26 mo) and disuse (hindlimb unloading). In agreement with previous studies,
      overall superoxide production increased with aging and disuse. On the other hand,
      the new experimental method revealed that superoxide production outside the
      mitochondria of the soleus does not show a significant age-related increase.
      Another observation was that the superoxide production increase in the matrix
      occurs earlier (7 days of disuse) compared with the outside mitochondria (14 days
      of disuse) in both muscle types. These findings indicate that superoxide release
      is complex as it occurs asymmetrically at both sides of the mitochondrial inner
      membrane, and that such release has muscle type and temporal specificity. These
      findings are important to refine current concepts on oxidative stress associated
      with muscle aging and disuse.

PMID- 20689099
TI  - The Wiskott-Aldrich syndrome protein regulates CTL cytotoxicity and is required
      for efficient killing of B cell lymphoma targets.
AB  - WAS is a primary immunodeficiency as a result of mutations in the gene encoding
      the WASP, a key actin regulator of hematopoietic cells. Whether killing defects
      in CD8(+) CTLs contribute to WAS-associated immunodeficiency and susceptibility
      to tumor development remains to be explored. CTL lines from WAS patients,
      generated by repeated stimulation with SAg-loaded B-EBV, displayed reduced
      production of cytokines (IL-2, IFN-gamma, and TNF-alpha) but almost normal
      proliferation upon SAg stimulation. Although WAS CTLs killed target B cells in a
      SAg dose-dependent manner, their efficiency was reduced, especially at a low SAg
      dose. The cytotoxic efficiency of WAS CTLs was particularly reduced against
      tumoral B cell lines. WAS CTLs expressed normal levels of lytic molecules and
      demonstrated efficient exocytosis upon target cell encounter. However, the lytic
      granules appeared not to fully polarize toward the center of the CTL/tumor target
      cell contact area. Importantly, the use of a gene therapy lentiviral vector was
      sufficient to restore efficient cytotoxic activity. Our study suggests that CTL
      dysfunction contributes to the development of hematological malignancies in WAS
      patients.

PMID- 20689100
TI  - Addressing maternal fatigue: a challenge to in-hospital breastfeeding promotion.

PMID- 20689101
TI  - Storage of human milk: accepting certain uncertainties.

PMID- 20689102
TI  - Breastfeeding women's experience of expressing: a descriptive study.
AB  - There is an increasing trend in Australia and elsewhere for mothers to express
      breast milk. The purpose of this study was to explore breastfeeding women's
      experiences of expressing breast milk. An anonymous online questionnaire was sent
      to Victorian members of the Australian Breastfeeding Association via an e-mail
      link. Response fraction was 903 of 3024 (29.9%). The most common reason for
      expressing milk was to "store extra breast milk" (57%, 479/836). The most
      important reason was "not enough milk"/"to make more milk" (15%, 118/771). The
      majority of women (65%, 666/843) used an electric breast pump, and this method of
      expressing was preferred by 59% (454/769) of women. Adverse effects of pumps were
      pain (17%, 126/737) and damage to nipples (11%, 86/737). Breast pumps may have a
      role in enabling women to extend the duration of breast milk feeding, but further
      research is needed.

PMID- 20689103
TI  - Factors associated with breastfeeding duration among Connecticut Special
      Supplemental Nutrition Program for Women, Infants, and Children (WIC)
      participants.
AB  - This retrospective study aimed to identify factors associated with breastfeeding
      duration among women enrolled in the Special Supplemental Nutrition Program for
      Women, Infants, and Children (WIC) of Hartford, Connecticut. The authors included
      mothers whose children were younger than 5 years and had stopped breastfeeding (N
      = 155). Women who had planned their pregnancies were twice as likely as those who
      did not plan them to breastfeed for more than 6 months (odds ratio, 2.15; 95%
      confidence interval, 1.00-4.64). One additional year of maternal age was
      associated with a 9% increase on the likelihood of breastfeeding for more than 6
      months (odds ratio, 1.09; 95% confidence interval, 1.02-1.17). Time in the United
      States was inversely associated with the likelihood of breastfeeding for more
      than 6 months (odds ratio, 0.96; 95% confidence interval, 0.92-0.99). Return to
      work, sore nipples, lack of access to breast pumps, and free formula provided by
      WIC were identified as breastfeeding barriers. Findings can help WIC improve its
      breastfeeding promotion efforts.

PMID- 20689104
TI  - Psychometric evaluation of the Employer Support for Breastfeeding Questionnaire
      (ESBQ).
AB  - The purpose of this descriptive methodological study was to develop and evaluate
      the psychometric properties of the Employer's Support for Breastfeeding
      Questionnaire (ESBQ). The convenience sample consisted of 380 business owners,
      managers, or supervisors from the Midwestern United States. Data were collected
      using Web and paper-based questionnaires from January to March 2008. Psychometric
      evaluation included item analysis, scale reliability, and construct validity. The
      ESBQ subscales had Cronbach's alphas ranging from 0.85 to 0.92. Most inter-item
      and item-to-total correlations were above the recommendation of 0.30. The test
      retest reliability of each subscale ranged from 0.93 to 1.0. Confirmatory factor
      analysis supported the construct validity of the scale. The comparative fit index
      (CFI) and the non-normal fit index (NNFI) were 0.90 and 0.91, respectively, and
      the root mean square error of approximation (RMSEA) was 0.05. Findings supported
      the ESBQ as reliable, valid, and theoretically consistent with the theory of
      planned behavior.

PMID- 20689106
TI  - The costs of suboptimal breastfeeding.

PMID- 20689105
TI  - ILCA's inside track a resource for breastfeeding mothers: twins.

PMID- 20689107
TI  - Safety and efficacy of pulmonary vein antral isolation in patients with
      obstructive sleep apnea: the impact of continuous positive airway pressure.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) may be associated with pulmonary vein
      antrum isolation (PVAI) failure. The aim of the present study was to investigate
      if treatment with continuous positive airway pressure (CPAP) improved PVAI
      success rates. METHODS AND RESULTS: From January 2004 to December 2007, 3000
      consecutive patients underwent PVAI. Patients were screened for OSA and CPAP use.
      Six hundred forty (21.3%) patients had OSA. Patients with OSA had more procedural
      failures (P=0.024) and hematomas (P<0.001). Eight percent of the non-OSA
      paroxysmal atrial fibrillation patients had nonpulmonary vein antrum triggers
      (non-PV triggers) and posterior wall firing versus 20% of the OSA group
      (P<0.001). Nineteen percent of the non-OSA nonparoxysmal atrial fibrillation
      population had non-PV triggers versus 31% in the OSA group (P=0.001). At the end
      of the follow-up period (32+/-14 months), 79% of the non-CPAP and 68% of the CPAP
      group were free of atrial fibrillation (P=0.003). Not using CPAP in addition to
      having non-PV triggers strongly predicted procedural failure (hazard ratio, 8.81;
      P<0.001). CONCLUSIONS: OSA was an independent predictor for PVAI failure.
      Treatment with CPAP improved PVAI success rates. Patients not treated with CPAP
      in addition to having higher prevalence of non-PV triggers were 8 times more
      likely to fail the procedure.

PMID- 20689108
TI  - 2010 Report of the Executive Vice President and Chief Executive Officer: keeping
      our focus during a difficult time.

PMID- 20689109
TI  - 2010 Report of the ASHP Treasurer: recovery...stability...strength.

PMID- 20689110
TI  - Professional policies approved by the 2010 ASHP House of Delegates.

PMID- 20689113
TI  - FDA advisers recommend new controls on rosiglitazone use.

PMID- 20689114
TI  - Buprenorphine transdermal system has REMS.

PMID- 20689116
TI  - FDA works toward product naming, packaging guidance.

PMID- 20689117
TI  - Leapfrog Group wants hospitals to monitor, not just implement, CPOE systems.

PMID- 20689118
TI  - Pharmacist involvement in fall prevention.

PMID- 20689119
TI  - Role of the pharmacist in a presurgical clinic designed to optimize outcomes
      after elective total joint arthroplasty.

PMID- 20689120
TI  - A dream deferred.

PMID- 20689121
TI  - Liraglutide: a once-daily human glucagon-like peptide-1 analogue for type 2
      diabetes mellitus.
AB  - PURPOSE: The pharmacology, pharmacokinetics, efficacy, safety, dosage and
      administration, adverse effects, and place in therapy of liraglutide, a glucagon
      like peptide-1 (GLP-1) receptor agonist, are reviewed. SUMMARY: Liraglutide, the
      first once-daily human GLP-1 analogue, retains 97% homology with the endogenous
      hormone and shares its glucose-dependent glucose-lowering action but has a
      considerably longer half-life that supports once-daily dosing. After promising
      Phase II study results, the Liraglutide Effect and Action in Diabetes (LEAD)
      Phase III clinical development program, involving more than 4000 patients
      worldwide, investigated the efficacy and tolerability of liraglutide 1.2 or 1.8
      mg daily (n = 2735) as monotherapy and in combination with various oral
      antidiabetic drugs. The LEAD studies yielded encouraging results indicating that
      patients receiving liraglutide could expect to attain glycosylated hemoglobin
      reductions of about 1-1.5% and fasting plasma glucose reductions of 15-43 mg/dL.
      Loss of body weight was consistent throughout the studies: when using liraglutide
      1.8 mg as monotherapy, patients lost a mean of 2.5 kg over a 52-week period.
      Accompanying reductions in some cardiovascular risk endpoints, such as systolic
      blood pressure, were also observed. By virtue of its glucose-dependent mode of
      action, liraglutide was generally well tolerated in clinical trials, with only
      very rare episodes of major hypoglycemia reported. The most frequently observed
      adverse effects were gastrointestinal, with 10-40% of patients experiencing an
      episode of nausea, which was often mild or moderate in severity and transient in
      nature. CONCLUSION: Liraglutide is efficacious and well tolerated in patients
      with type 2 diabetes and has been found to reduce weight and blood pressure.

PMID- 20689122
TI  - Evaluating equivalence and noninferiority trials.
AB  - PURPOSE: The conceptual issues related to the design of equivalence and non
      inferiority trials and considerations for interpreting the findings of such
      trials are described. SUMMARY: Comparative effectiveness research (CER) has
      recently gained importance in the evaluation of different treatment alternatives.
      Large, prospective, randomized controlled trials (RCTs) conducted with patient
      populations under routine practice conditions can yield high-quality CER results.
      A Phase III RCT, usually conducted for establishing superiority of one treatment
      over another, is called a superiority trial, and the statistical test associated
      with it is known as a superiority test. In a pragmatic equivalence trial, a
      researcher aims to test if two treatments are identical (within a specified
      range) with respect to some predefined clinical criteria. Pragmatic
      noninferiority trials aim to show if a test therapy is no worse than a standard
      therapy with respect to achieving the primary treatment outcome. A nonsignificant
      result obtained from a superiority test does not indicate that the two treatment
      options are similar. In other words, the lack of evidence of superiority does not
      guarantee a lack of difference in the performance shown by the therapies. A
      researcher can only demonstrate identical effects of two treatments in an
      equivalence trial. In a noninferiority trial, the test therapy is preferred when
      there is evidence about its benefits over the standard treatment in terms of
      secondary outcomes such as cost, adherence, and adverse effects. CONCLUSION:
      Equivalence and noninferiority trials are designed differently from superiority
      trials. The overall quality of equivalence and noninferiority studies depends on
      study design and the manner in which the results are reported.

PMID- 20689123
TI  - Commonly prescribed medications and potential false-positive urine drug screens.
AB  - PURPOSE: The implications of potential false-positive urine drug screen (UDS)
      results for patients receiving commonly prescribed medications were evaluated.
      SUMMARY: A comprehensive literature review was conducted to identify false
      positive UDSs associated with all clinic formulary medications, as well as common
      nonprescription medications. The references of each report describing a
      medication whose use was associated with false-positive UDS results were also
      reviewed. If a class effect was suspected, additional agents in the category were
      searched. A total of 25 reports of false-positive UDS results were identified.
      Categories of medications included antihistamines, antidepressants, antibiotics,
      analgesics, antipsychotics, and nonprescription agents. Reports of false-positive
      results were found for the following formulary and nonprescription medications:
      brompheniramine, bupropion, chlorpromazine, clomipramine, dextromethorphan,
      diphenhydramine, doxylamine, ibuprofen, naproxen, promethazine, quetiapine,
      quinolones (ofloxacin and gatifloxacin), ranitidine, sertraline, thioridazine,
      trazodone, venlafaxine, verapamil, and a nonprescription nasal inhaler. False
      positive results for amphetamine and methamphetamine were the most commonly
      reported. False-positive results for methadone, opioids, phencyclidine,
      barbiturates, cannabinoids, and benzodiazepines were also reported in patients
      taking commonly used medications. The most commonly used tests to screen urine
      for drugs of abuse are immunoassays, even though false-positive results for drugs
      of abuse have been reported with a number of these rapid-screening products.
      Results from such tests should be confirmed using additional analytical methods,
      including gas chromatography-mass spectrometry. CONCLUSION: A number of routinely
      prescribed medications have been associated with triggering false-positive UDS
      results. Verification of the test results with a different screening test or
      additional analytical tests should be performed to avoid adverse consequences for
      the patients.

PMID- 20689124
TI  - Angioedema after nonsteroidal antiinflammatory drug initiation in a patient
      stable on an angiotensin-converting-enzyme inhibitor.
AB  - PURPOSE: A case of angioedema associated with the initiation of a nonsteroidal
      antiinflammatory drug in a patient stable on an angiotensin-converting-enzyme
      inhibitor is reported. SUMMARY: A 68-year-old African-American man with no known
      drug allergies and a history of hypertension, benign prostatic hypertrophy,
      diverticulosis, and gout arrived at the clinic with swelling of the lips and
      tongue three days after he started taking naproxen 375 mg every eight hours as
      needed for pain associated with acute gout. He denied urticaria, difficulty
      breathing, fever, abdominal pain, vomiting, and diarrhea. His other medications
      included quinapril 10 mg daily (taken for 5 years), tamsulosin hydrochloride 0.4
      mg daily, omeprazole 20 mg daily, and colchicine 0.6 mg daily. He had reported
      smoking approximately 2.5 packs of cigarettes per week and consuming alcohol (one
      to two drinks) on the weekends. He denied any illicit drug use, drug rash, or
      seasonal allergies. Naproxen was discontinued, and the patient was treated with
      prednisone (tapered regimen) and acetaminophen 650-mg tablets, and his angioedema
      resolved. The Naranjo et al. probability scale revealed that naproxen and
      quinapril coadministration was the probable cause of the patient's adverse
      reaction (score of 7). CONCLUSION: A 68-year-old African-American man who had
      been receiving quinapril for 5 years developed angioedema after initiation of
      naproxen.

PMID- 20689125
TI  - Unique case of presumed lisinopril-induced hepatotoxicity.
AB  - PURPOSE: A case of presumed lisinopril-induced hepatotoxicity is reported.
      SUMMARY: A 30-year-old woman had complained of fatigue and yellow eyes for two
      days. Her medical history included hypertension and nephrotic syndrome. Her
      medications included furosemide 20 mg daily (for almost 6.5 years) and lisinopril
      10 mg daily (for eight months). She had been treated with quinapril, enalapril,
      and lisinopril in the past by different primary care physicians without any
      adverse effects. She did not abuse alcohol and denied any liver-related problems
      in the past. Her physical examination revealed icterus and right-upper-quadrant
      abdominal tenderness. Initial laboratory tests revealed elevated liver enzyme
      values. Ultrasonography and computed tomography (CT) scans of the patient's
      abdomen suggested hepatocellular disease with mild hepatomegaly and a normal
      biliary tract. Due to worsening bilirubin and liver enzyme values, lisinopril was
      stopped. In the absence of a probable cause of the patient's hepatotoxicity, a CT
      guided liver biopsy was performed. Histological examination of the liver tissue
      showed moderate chronic inflammatory cell infiltrates in the portal area,
      predominantly composed of lymphocytes with mild-to-moderate interface hepatitis.
      No centrolobular necrosis or steatosis was seen. After lisinopril was
      discontinued, there was a rapid improvement in the patient's clinical and
      biochemical pictures. On her follow-up clinic visit approximately two months
      later, all of her liver enzyme values had normalized. CONCLUSION: A woman who had
      received quinapril, enalapril, and lisinopril in the past without apparent
      adverse effects developed hepatocellular disease that became evident eight months
      after lisinopril therapy was reinstituted. The presumed hepatotoxicity resolved
      after discontinuation of lisinopril.

PMID- 20689126
TI  - Outcomes associated with transdermal nicotine replacement therapy in a
      neurosurgery intensive care unit.
AB  - PURPOSE: The outcomes associated with transdermal nicotine replacement therapy
      (NRT) in a neurosurgery intensive care unit (ICU) were studied. METHODS: Data
      from pharmacy records, neurosurgery ICU admission logs, and computerized patient
      charts at the University of Illinois Medical Center at Chicago from January 2001
      through August 2008 were reviewed for patients older than 18 years who were
      admitted to the neurosurgery ICU for neurologic insults. Patients were
      categorized into three groups: smokers who received transdermal NRT (n = 114),
      smokers who did not receive transdermal NRT (n = 113), and nonsmokers (n = 113).
      The primary outcome of this study was unfavorable disposition at discharge from
      the hospital. Secondary outcomes measured included overall mortality; lengths of
      hospital and neurosurgery ICU stays; and rates of subarachnoid hemorrhage (SAH)
      rebleeding, angiographic vasospasm, intracerebral hemorrhage rebleeding, and
      ischemic stroke. RESULTS: Overall, there was no difference in unfavorable
      discharge disposition among the three groups (p = 0.17). However, the group who
      received NRT had higher admission rates of SAH, smoked more cigarettes for a
      longer period of time, and had longer stays in the neurosurgery ICU and hospital
      compared with the other groups. All patients who received NRT had prolonged
      hospital (p = 0.014) and neurosurgery ICU (p = 0.006) stays compared with those
      who did not receive NRT. There were no differences in other secondary outcomes
      among the groups. CONCLUSION: There was no significant difference in unfavorable
      discharge disposition among neurosurgery ICU patients who were smokers treated
      with NRT, smokers not treated with NRT, and nonsmokers not treated with NRT.

PMID- 20689127
TI  - Medication therapy management and condition care services in a community-based
      employer setting.
AB  - PURPOSE: A program in which health-system pharmacists and pharmacy technicians
      provide medication therapy management (MTM), wellness, and condition care
      (disease management) services under contract with local businesses is described.
      SUMMARY: The health-system pharmacy department's Center for Medication Management
      contracts directly with company benefits departments for defined services to
      participating employees. The services include an initial wellness and MTM session
      and, for certain patients identified during the initial session, ongoing
      condition care. The initial appointment includes a medication history, point-of
      care testing for serum lipids and glucose, body composition analysis, and
      completion of a health risk assessment. The pharmacist conducts a structured MTM
      session, reviews the patient's test results and risk factors, provides health
      education, discusses opportunities for cost savings, and documents all activities
      on the patient's medication action plan. Eligibility for the condition care
      program is based on a diagnosis of diabetes, hypertension, asthma, heart failure,
      or hyperlipidemia or elevation of lipid or glucose levels. Findings are
      summarized for employers after the initial wellness screening and at six-month
      intervals. Patients receiving condition care sign a customized contract,
      establish goals, attend up to four MTM sessions per year, and track their
      information on a website; employers may offer incentives for participation. When
      pharmacists recommend adjustments to therapy or cost-saving changes, it is up to
      patients to discuss these with their physician. A survey completed by each
      patient after the initial wellness session has indicated high satisfaction.
      Direct cost savings related to medication changes have averaged $253 per patient
      per year. Total cost savings to companies in the first year of the program
      averaged $1011 per patient. For the health system, the program has been
      financially sustainable. Key laboratory values indicate positive clinical
      outcomes. CONCLUSION: A business model in which health-system pharmacists provide
      MTM and condition care services for company employees has demonstrated successful
      outcomes in terms of patient satisfaction, cost savings, and clinical benefits.

PMID- 20689128
TI  - Educational program for pharmacists at a multifacility academic medical center.
AB  - PURPOSE: An educational program for pharmacists in a multifacility health care
      setting is described. SUMMARY: The expansion of pharmacy services at a university
      medical center from a centralized to a decentralized, unit-based model created
      the need for enhanced education of staff pharmacists. A steering committee with
      pharmacy department and school of pharmacy representation surveyed educational
      and professional needs related to the expanded services. Pharmacists indicated
      that they needed an educational program that was comprehensive, interactive, and
      accessible to all shifts. Pharmacy school clinical faculty members provided most
      of the initial educational sessions, which combined didactic presentations and
      case-based discussion. The needs survey was used in selecting topics that were
      most relevant to the pharmacists' expanded practice. Each major topic was covered
      in a series of one-hour sessions held at two-week intervals and scheduled at a
      time convenient for afternoon-shift pharmacists. Incentives were offered to
      encourage participation. The live presentations were recorded with video
      streaming technology and made available via the Internet to pharmacists on all
      shifts in all facilities of the health system as well as to faculty members.
      Since program implementation in 2005, attendance at the live sessions has
      averaged 25. In postimplementation surveys, pharmacists indicated that the
      program was meeting their needs and improving patient care. Since 2008,
      pharmacists have been able to earn continuing-education (CE) credit for the
      sessions. CONCLUSION: A collaborative educational series with online access,
      clinical content, and CE credit has been effective in meeting pharmacists' needs
      in a multifacility health care setting.

PMID- 20689129
TI  - Inaugural address of the President-elect. The "University of ASHP": teaching and
      learning in a new world of practice.

PMID- 20689130
TI  - Management of medication use in Scotland.

PMID- 20689131
TI  - Morphoproteomics demonstrates activation of mTOR pathway in anaplastic thyroid
      carcinoma: a preliminary observation.
AB  - The mammalian target of rapamycin (mTOR) signaling pathway was studied using
      immunohistochemical stains on paraffin-embedded tumor tissue from two patients
      with anaplastic thyroid carcinoma (ATC) and on paraffin-embedded normal thyroid
      tissue from 23 control patients. Immunoreactivities of p-mTOR, p-Akt, p-p70S6K,
      and PLD1 were observed in both of the ATCs, with nuclear translocation of p-mTOR,
      p-Akt, and p-p70S6K. Increased expression of Ki-67, Skp2, and cyclin D1,
      decreased expression of p27(kip1), and increased mitotic index (MI) were noted in
      the ATCs in comparison with those of normal thyroid tissue. The results provide
      evidence of (a) constitutive activation of the mTOR pathway, (b) mTORC2
      activation, suggested by the nuclear translocation of p-mTOR, and (c) enhanced
      cell cycle progression in ATCs. These preliminary findings warrant future studies
      in a large series of patients with ATC to evaluate a possible molecular basis for
      treating chemoradioresistant ATC.

PMID- 20689132
TI  - Proteomics and biomarkers for ovarian cancer diagnosis.
AB  - Ovarian cancer remains a leading cause of death from gynecological malignancy.
      Early diagnosis is the most important determinant of survival. Current diagnostic
      tools have had very limited success in early detection. In recent years, the
      advancing techniques for proteomics have accelerated the discovery of ovarian
      cancer biomarkers. Numerous proteomics-based molecular biomarkers/panels have
      been identified and hold great potential for diagnostic applications, but they
      need further development and validation. This article reviews recently published
      data on the diagnosis of ovarian cancer with proteomics, including the major
      proteomics technologies and promising strategies for biomarker discovery and
      development.

PMID- 20689133
TI  - Quantitation of CD55 and CD59 expression on reticulocytes and mature erythrocytes
      in paroxysmal nocturnal hemoglobinuria, aplastic anemia, and healthy control
      subjects.
AB  - Since PNH occasionally results in bone marrow failure, it is difficult to
      differentiate PNH from AA with small numbers of CD(55) (-)CD(59) (-)
      erythrocytes. We quantified CD55 and CD59 molecules expressed on normal
      reticulocytes and mature erythrocytes of paroxysmal nocturnal hemoglobinuria
      (PNH), aplastic anemia (AA), and normal individuals in order to determine their
      usefulness for differentiation between PNH and AA. A total of 56 patients (AA 39
      patients, PNH 17 patients) and 10 healthy volunteers were enrolled. Two-color
      flow cytometric analyses were conducted using thiazole orange, anti-CD55 and CD59
      monoclonal antibodies to identify CD(55) (-)CD(59) (-) reticulocytes and mature
      erythrocytes. Mean fluorescence level of CD(55) (+) mature erythrocytes was
      lowest in the PNH patients (13.2 x 10(3) MESF), and was significantly lower than
      in normal controls (16.7 x 10(3) MESF, p <0.05), and highest in the AA subjects
      (22.8 x 10(3) MESF). Mean fluorescence level of CD(59) (+) mature erythrocytes
      was lowest in the PNH subjects (24.5 x 10(3) MESF), significantly less than in
      normal controls (39.0 x 10(3) MESF, p <0.05), and highest in the AA subjects
      (49.2 x 10(3) MESF). Total reticulocyte counts correlated strongly with the
      CD(55) (-)CD(59) (-) reticulocytes. Comparative quantitative analysis of CD55 and
      CD59 molecules expressed on normal erythrocytes may be useful in differentiating
      PNH from AA patients with small numbers of PNH-phenotype erythrocytes, and the
      total reticulocyte count may prove useful as a marker for PNH clone size.

PMID- 20689134
TI  - Activation of nuclear factor-erythroid 2-related factor 2 (Nrf2) in the basilar
      artery after subarachnoid hemorrhage in rats.
AB  - Cerebral vasospasm plays a pivotal role in the outcome of patients suffering from
      subarachnoid hemorrhage (SAH). The mechanisms underlying cerebral vasospasm are
      complex and interrelated. Previous studies that focused on only one of these
      mechanisms have proved to be ineffective in clinical practice. Therefore, a
      therapeutic target is desirable that can interrupt the multi-mechanisms
      underlying cerebral vasospasm. Nuclear factor-erythroid 2-related factor 2 (Nrf2)
      has been shown to be a key regulator in reducing oxidative stress, inflammatory
      damage, and accumulation of toxic metabolites, which are all involved in SAH
      induced cerebral vasospasm. However, whether Nrf2 is activated in the cerebral
      artery after SAH hasn't been studied. In the present study, 30 male rats were
      randomly divided into two groups: control group (n = 15) and SAH group (n = 15).
      The animals in the SAH group were subjected to injection of autologous blood into
      the cisterna magna twice on day 0 and day 2 and were killed on day 5. The cross
      sectional area of the basilar artery was measured and the nuclear Nrf2 protein
      level was studied by Western blot, electrophoretic mobility shift assay (EMSA),
      and immunohistochemical techniques. The expression of nuclear Nrf2 protein was
      increased remarkably in the SAH group compared with the control group.
      Immunohistochemical staining demonstrated that high level expression of Nrf2 was
      present in endothelial and smooth muscle cells; it was located in both the nuclei
      and cytoplasm. The results of this study indicate that Nrf2 expression is up
      regulated in the cerebral artery of rats after experimental SAH.

PMID- 20689135
TI  - Hydroxyethyl starch 130/0.4 exerts its anti-inflammatory effect in endotoxemic
      rats by inhibiting the TLR4/NF-kappaB signaling pathway.
AB  - Previous studies demonstrated that hydroxyethyl starch (HES) down-regulates the
      inflammatory response, but the mechanism is controversial. The present study
      measured the effects of HES130/0.4 on plasma proinflammatory cytokines levels and
      the Toll-like receptor-4 (TLR4)/nuclear factor-kappa B (NF-kappaB) signaling
      pathway in lipopolysaccharide (LPS)-treated rats. Endotoxemia was induced in rats
      by injection of LPS (5 mg/kg, via tail vein) and the rats were infused with
      different doses of HES130/0.4 (7.5, 15, or 30 ml/kg, via jugular vein). At 2 hr
      after the injection of LPS, plasma and peripheral monocytes were collected to
      determine tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta
      concentrations (enzyme-linked immunosorbent assay), NF-kappaB activities
      (electrophoretic mobility shift assay), TLR4 mRNA expression (reverse
      transcription-polymerase chain reaction), and TLR4 protein levels (Western
      blotting). The infusion of HES130/0.4 in endotoxemic rats, especially 15 ml/kg,
      significantly reduced the release of plasma TNF-alpha and IL-1beta, which was
      consistent with the observed inhibitory effects of HES130/0.4 on NF-kappaB
      activation, TLR4 mRNA expression, and TLR4 protein level in monocytes. Thus,
      HES130/0.4 evidently exerts its anti-inflammatory effect in endotoxemic rats by
      inhibiting the TLR4/NF-kappaB signaling pathway, which suggests that HES130/0.4
      may useful for treating early Gram-negative sepsis.

PMID- 20689136
TI  - Accuracy of CoaguChek XS for point-of-care antithrombotic monitoring in children
      with heart disease.
AB  - The CoaguChek XS international normalized ratio (INR) assay was compared to INR
      assay by a standard laboratory method in children with heart disease on
      anticoagulant therapy. The data comprised 120 pairs of INR values for 42 patients
      (age <16 yr) who attended a cardiology clinic between 1 May 2007 and 30 January
      2008. Parallel INR assays by the CoaguChek XS and the standard method were
      performed within 1 hr by a single qualified technician and the paired results
      were evaluated by linear regression and Bland-Altman analysis. The mean
      difference in the INR values was -0.08 +/- 0.04 units (p = 0.63); the difference
      between the two results was consistently <0.5 INR units. The slope of the
      regression line was 0.98 (95% CI: 0.96 to 1.01) and the y-intercept was 0.014
      (95% CI: -0.01 to 0.04). In the Bland-Altman analysis, the mean difference in INR
      between the two methods was 0.08 units and values for 99.4% of the patients fell
      within the limit of agreement (-0.17 to 0.28 units). In summary, INR assays in
      children by the CoaguChek XS device are as accurate as the standard method, but
      faster and more convenient.

PMID- 20689137
TI  - Evaluation of commercial selective agars in screening for methicillin-resistant
      Staphylococcus aureus.
AB  - To evaluate methicillin-resistant S. aureus (MRSA) detection methods, we compared
      (a) mannitol salt agar with cefoxitin (MSA-FX), (b) MRSASelect agar (Bio-Rad),
      (c) MRSA ID (bioMerieuex), and (d) CHROMagar MRSA (BD Diagnostics) as selective
      media for culturing nasal swab specimens collected from intensive care unit (ICU)
      patients and healthcare personnel. A total of 99 (17.1%) cases of MRSA were
      recovered from 578 specimens. Four (5.5%) cases were identified from healthcare
      personnel and 95 (18.8%) were from ICU patients. The sensitivity of MSA-FX,
      MRSASelect, MRSA ID, and CHROMagar MRSA was 83.8, 87.9, 80.8, and 84.8% after 18
      hr; 92.9, 94.9, 90.9, and 91.9% after 24 hr; and 96.0, 100, 99.0, and 99.0% after
      48 hr, respectively. The specificity of MSA-FX, MRSASelect, MRSA ID, and
      CHROMagar MRSA was 97.7, 99.0, 98.7. and 99.8% after 18 hr; 97.1, 98.5, 98.1, and
      99.5% after 24 hr; and 95.2, 97.7, 97.9, and 99.0% after 48 hr, respectively. In
      conclusion, all four media showed good results after the 24 hr readings, but MRSA
      ID and CHROMagar MRSA media required readings at 48 hr due to increased
      sensitivity at this time point.

PMID- 20689138
TI  - Stability of human stromal-derived factor-1alpha (CXCL12alpha) after blood
      sampling.
AB  - Stromal-derived factor 1-alpha (SDF-1alpha, or CXCL12alpha) is a major chemokine
      that controls adult stem cell trafficking. Little is known about its stability
      after blood sampling, but this is a crucial issue for clinical studies of this
      molecule. In a study of six subjects, we found total human plasma SDF-1alpha
      concentrations to be stable for 120 min when the blood is placed on ice
      immediately after sampling.

PMID- 20689139
TI  - Clinical, biochemical, and genetic analysis of korean patients with
      pseudohypoparathyroidism type Ia.
AB  - Pseudohypoparathyroidism (PHP) comprises a heterogeneous group of endocrine
      disorders with the common feature of resistance to parathormone (PTH), manifested
      by hypocalcemia, hyperphosphatemia, and elevation of serum PTH despite normal
      renal function. Herein, the first Korean cases of PHP type Ia are reported. The
      two patients (6-yr-old female, 7-yr-old male) had typical signs of Albright
      hereditary osteodystrophy. Genomic DNA was isolated from their peripheral blood
      leukocytes and the GNAS gene was amplified by PCR and analysed by bidirectional
      sequencing including all coding exons. Two GNAS mutations were found: c.94A>T and
      c.344_345insT. Patient 1 had a nonsense mutation of c.94A>T (p. K32X), which has
      not been previously described; the mother also had c.94A>T, and it therefore was
      a familial mutation. Patient 2 had a known frame shift mutation for c.344_345insT
      (p.V117RfsX23). The family members of patient 2 had wild-type sequences. In
      summary, two Korean patients with PHP-Ia were confirmed by genetic analysis and a
      novel p.K32X product of the GNAS mutation was identified.

PMID- 20689141
TI  - Constitutional pericentric inversion 9 and hematological disorders: a Korean
      tertiary institution's experience over eight years.
AB  - Constitutional pericentric inversion of chromosome 9 [inv(9)] occurs in 0.8 to 2%
      of the normal population and has long been considered a normal variant. It is
      controversial whether inv(9) is a predisposing factor for acute leukemia (AL).
      The effect of inv(9) on bone marrow (BM) recovery after stem cell transplantation
      or chemotherapy is undetermined. Between March 2001 and December 2008, the
      cytogenetics of 3,809 patients with suspected hematological diseases were
      reviewed. Of them, 586 patients were diagnosed with AL. Constitutional inv(9) was
      found in 55 patients with various hematological disorders, including AL and solid
      tumors. The proportion of inv(9) was similar in patients with AL (8/586, 1.37%)
      and those without (47/3223, 1.46%; p = 1.0). Of the eight patients with AL and
      inv(9), one refused treatment and seven had induction chemotherapy. Four of the
      seven patients achieved prompt hematological recovery, but the other three failed
      to achieve complete hematological remission. Thus constitutional inv(9) seems not
      to be related independently to delayed hematological recovery. One recipient of
      an allogeneic peripheral blood stem cell transplantation, from an unrelated donor
      with constitutional inv(9), also achieved prompt hematological reconstruction,
      further suggesting that constitutional inv(9) has no effect on hematopoietic
      cells. In summary, our data suggest that constitutional inv(9) is a truly random
      chromosomal aberration with no apparent functional effect on hematological
      disorders.

PMID- 20689140
TI  - Homozygous deletion but not mutation of exons 5 and 8 of the fragile histidine
      triad (FHIT) gene is associated with features of differentiated thyroid
      carcinoma.
AB  - The fragile histidine triad (FHIT) gene encompasses the most common human fragile
      site, FRA3B at 3p14.2, a region that is involved in homozygous deletions in a
      variety of human tumors. FHIT is considered to be a tumor suppressor gene that is
      frequently inactivated in various types of cancer. To study the role of the FHIT
      gene in thyroid tumorigenesis, we looked for homozygous deletions or mutations of
      exons 5 and 8 of the FHIT gene in 65 cases of differentiated thyroid carcinoma
      (DTC) and their matched non-cancerous epithelium (NCE), using exon-specific PCR
      amplification and PCR single strand conformation polymorphism (PCR-SSCP)
      techniques. In DTC, the incidence of homozygous deletion of exon 5 was 30.8%
      (20/65), and it was associated with tumor metastasis to lymph nodes (p <0.05).
      The incidence of homozygous deletion of exon 8 was 29.2% (19/65), and it was
      associated with the tumor pathological grade, TNM stage, and lymph node
      metastasis (p <0.05). There was strong correlation between homozygous deletions
      of exon 5 and exon 8 (p <0.01). No point mutations were observed in either exon 5
      or exon 8. These findings suggest that: (a) exons 5 and 8 of FHIT are key target
      regions of deletion, (b) homozygous deletions of exon 5 and exon 8 may be good
      biomarkers for the biological behavior of DTC, and (c) point mutation of these
      exons may not be involved in the inactivation of the FHIT gene in DTC.

PMID- 20689142
TI  - Clinical, pathological, and genetic analysis of a Korean family with thoracic
      aortic aneurysms and dissections carrying a novel Asp26Tyr mutation.
AB  - Non-syndromic familial thoracic aortic aneurysms and dissections (TAADs),
      inherited in an autosomal dominant manner in up to 19% of patients, are
      genetically heterogeneous. The ACTA2 gene, which encodes the vascular smooth
      muscle cell (SMC)-specific isoform of alpha-actin, is known to cause TAADs and
      occlusive vascular diseases, including coronary artery disease and premature
      ischemic stroke. We have investigated a Korean family with DeBakey type I aortic
      dissection related to pregnancy and a strong family history of TAADs. All
      affected family members underwent surgical repair of the ascending aorta. Other
      clinical features of familial TAAD, including inguinal hernias, iris flocculi,
      and livedo reticularis, were not observed. Histologic studies of aortic tissues
      showed medial degeneration and SMC hyperplasia in the aorta, consistent with
      previous observations. Molecular analyses of the ACTA2 gene showed a novel
      heterozygous missense mutation (c.76G>T; p.Asp26Tyr). Further analysis of a
      female patient and members of her family revealed that two affected sisters and
      her asymptomatic son had the same mutation. The novel Asp26Tyr mutation resides
      in SM alpha-actin subdomain 1 and is linked to TAAD with hypertrophy and disarray
      of SMCs and severe migraine, but not to livedo reticularis or iris flocculi. This
      study expands the spectrum of mutations of the ACTA2 gene by identifying a novel
      missense mutation. This is the first report of a pathologically- and genetically
      confirmed family with TAAD in Korea.

PMID- 20689143
TI  - Identification of a novel MYBPC3 gene variant in a patient with hypertrophic
      cardiomyopathy.
AB  - Hypertrophic cardiomyopathy (HCM) is a genetic disorder characterized by cardiac
      hypertrophy caused by mutations in sarcomere protein genes. MYBPC3 mutations are
      reported as a frequent cause of HCM. We aimed to identify the gene mutation
      underlying HCM in an Italian patient and his family composed of 13 relatives.
      Mutation screening of 658 known mutations was performed using a rapid and
      efficient mutation detection system based on semiautomated MALDI-TOF mass
      spectrometry using the Sequenom MassArray System and iPLEX Gold genotyping
      chemistry. Subsequently, direct sequencing of the coding exons and flanking
      intronic regions was performed for the most suitable HCM genes (MYBPC3, MYH7,
      TNNT2, TNNI3, and TPM1) in the index patient. We found a novel MYBPC3 gene
      mutation: G13999T (Gln689His). No other sarcomere gene mutation was found in this
      family. This genetic variant, which changes the last amino acid of MYBPC3 exon
      21, affects a highly conserved residue. Furthermore, the Gln689His does not
      appear in public databases and has never been described as a polymorphism. The
      potential pathogenic role of this novel mutation was underlined by its absence in
      a sample of healthy subjects (n = 122) from the general Italian population. In
      summary, a novel MYBPC3 gene mutation has been identified in a patient affected
      by HCM, whereas it was absent in 244 reference alleles.

PMID- 20689144
TI  - A novel KRIT1 gene mutation in a patient with cerebral and multiple spinal
      cavernous malformations.
AB  - Cavernous malformations (CMs) occur most often in the brain, but they have also
      been observed in extracranial regions. The synchronous finding of CMs in both the
      brain and spinal cord is rare. Furthermore, multiple spinal cord CMs are
      exceedingly rare, with only one reported case in Korea. Here, we present a 65-yr
      old Korean male with cerebral CMs (CCMs) and multiple spinal CMs. The patient
      complained of a gait disturbance and left foot paresthesia. The lesions involved
      the entire neuraxis, including the temporal lobe, right thalamus, and the
      cervical, thoracic, and lumbar spinal cord. Molecular analysis of the KRIT1
      (CCM1) gene identified a novel heterozygous frameshift mutation (c.816delG; p.
      Arg273GlufsX3) in the KRIT1 gene. Although genetic analyses were not performed in
      the patient's family members, the family history of cerebral hemorrhage in his
      mother, sons, sister, and the sister's sons suggests an autosomal dominant
      inheritance of the mutation. This study reveals a novel mutation of the KRIT1
      gene related to CCM and multiple spinal CMs. Based on these findings, molecular
      diagnosis might be beneficial for early diagnosis and treatment of the family
      members.

PMID- 20689145
TI  - An SRY-deleted XXY female resulting from a paternally inherited t(Y;22).
AB  - We report a case of a female with SRY-negative XXYp-. The karyotype by the
      conventional method revealed chromosome 22 with a short arm enlargement. The
      enlarged short arm contained a heterochromatic region, which was found by the
      whole chromosome painting method to be a part of the Y chromosome without the P
      arm. Chromosome study of the parents revealed that the t(Y;22) chromosome was
      derived from the patient's father who was phenotypically normal. Although the Y
      fragment was transmitted in patrilinear fashion in this case, our patient with
      intact copies of both X chromosomes and the Y chromosome with a deleted p arm is
      expected to show normal fertility. However, the patient should be closely
      followed in regard to fertility and the possibility of developing a
      gonadoblastoma.

PMID- 20689146
TI  - Superwarfarin intoxication of unknown etiology accompanying hemoperitoneum in a
      patient on fluconazole therapy.
AB  - We report a case of brodifacoum (superwarfarin) intoxication of unknown etiology
      presenting as hemoperitoneum after fluconazole administration for one week before
      the onset of symptoms. The initial prothrombin time (PT) and partial
      thromboplastin time (PTT) were markedly prolonged, although a mixing study with
      normal plasma showed that the corrected PT and PTT were in the normal range.
      Vitamin K-dependent coagulation factors (Factors II (5%), VII (8%), IX (4%), and
      X (6%)), and Protein C (16%) and Protein S (19%) activities were reduced.
      Although the patient denied ingesting rodenticides or medications other than an
      antifungal drug, fluconazole, superwarfarin toxicity was suspected; subsequently,
      his serum brodifacoum level was found to be positive. After administration of
      fresh frozen plasma (FFP) and oral vitamin K(1) for five days and following
      drainage of the hemoperitoneum, the patient's bleeding tendency stopped, with
      slow decreases in PT and PTT. Compared to previous reports of superwarfarin
      intoxication of unknown exposure, this case is distinct in that the severe
      bleeding tendency needed surgical management and involved a suspected drug
      interaction with fluconazole. Therefore, superwarfarin intoxication should be
      suspected in subjects with markedly prolonged PT and PTT of unknown etiology,
      since a drug interaction could amplify the toxicity from a small exposure to
      superwarfarin.

PMID- 20689147
TI  - Noted pathologists and laboratory scientists who attained advanced age.

PMID- 20689148
TI  - Pharmacists' role in ensuring safe and effective hospital use of insulin.
AB  - PURPOSE: To highlight the potential errors that may occur with insulin use in the
      inpatient setting and to describe how pharmacists can be part of the solution by
      implementing practices that reduce the likelihood of insulin-related medication
      errors. SUMMARY: Insulin is a drug with a low therapeutic index, and it bears a
      heightened risk of causing significant patient harm when used in error, making it
      a high-alert medication. Both underdosing and overdosing of insulin may be
      associated with adverse outcomes. The use of standard insulin order sets for
      scheduled subcutaneous insulin administration and standard concentrations for
      i.v. insulin are recommended to ensure the safe use of this medication. Any
      ambiguous insulin therapy orders should be clarified in writing prior to
      administration. Preparation of all insulin infusions should occur within the
      pharmacy. Pharmacists should be aware of possible medication errors related to
      inappropriate use of abbreviations such as U for units. Safe insulin storage
      practices are recommended to reduce the risk for insulin error. Insulin pen
      delivery devices may be used in hospitals, but safe use depends on ongoing
      oversight by a multidisciplinary committee, introduction of one device at a time,
      and initial and regular follow-up education of nurses, including agency nurses
      and those who work part-time. In addition, ongoing monitoring is needed to assure
      ongoing safety. The use of sliding-scale insulin can lead to hyperglycemia and
      hypoglycemia and is confusing and prone to error; it is not recommended.
      CONCLUSION: Pharmacists can contribute to the safe use of insulin in the
      inpatient setting by minimizing the likelihood of medication errors related to
      prescribing, transcription, dispensing, administration, storage, and
      communication.

PMID- 20689149
TI  - Important updates on the management of inpatient hyperglycemia: practical
      implications for pharmacists. Introduction.

PMID- 20689151
TI  - Reexamining the evidence for inpatient glucose control: new recommendations for
      glycemic targets.
AB  - PURPOSE: To review the risks of hyperglycemia in hospitalized patients, data
      supporting the benefits of treating hyperglycemia, and recommendations from the
      2009 American Association of Clinical Endocrinologists and American Diabetes
      Association consensus statement on the management of inpatient hyperglycemia.
      SUMMARY: Inpatient hyperglycemia is common, costly, and associated with poor
      clinical outcomes in many disease states. Despite inconsistencies in clinical
      trial results, good glucose management in the hospital remains important. Target
      blood glucose concentrations (BGs) were recently modified to somewhat higher
      values with the expectation that the benefit of treatment will persist with a
      lower risk of hypoglycemia, which is itself another marker of poor outcome in
      critically and non-critically ill patients. In the intensive care unit (ICU), the
      threshold to start treatment is a BG of <or=180 mg/dL. I.V. insulin is the
      treatment of choice in critically ill patients because of its rapid onset and
      offset of action. Once i.v. insulin is started, the BG should be maintained
      between 140 and 180 mg/ dL; a lower BG target (110-140 mg/dL) may be appropriate
      in selected patients. Targets of <110 mg/dL or >180 mg/dL are no longer
      recommended. In non-critically ill patients, premeal BG targets are <140 mg/dL;
      random BGs of <180 mg/dL are recommended. Scheduled subcutaneous insulin is the
      treatment of choice for hyperglycemia in non-critically ill patients; use of
      sliding-scale insulin is strongly discouraged. To avoid hypoglycemia, insulin
      regimens should be reassessed if BG falls to <100 mg/dL. CONCLUSION: Poor
      glycemic control in the hospital setting is a quality-of-care, safety, and cost
      issue. Safe and effective strategies to implement optimal glycemic control
      require multidisciplinary involvement. Insulin given i.v. in the ICU or
      subcutaneously on an as-scheduled regimen in other parts of the hospital is the
      treatment of choice.

PMID- 20689152
TI  - Ensuring optimal insulin utilization in the hospital setting: role of the
      pharmacist.
AB  - PURPOSE: To summarize essential information for the hospital pharmacist to
      support the safe and effective use of insulin for the treatment of inpatient
      hyperglycemia. SUMMARY: Ensuring optimal insulin utilization in the hospital
      setting requires collaboration of a multidisciplinary team, including physicians
      (and endocrinologists specifically), nurses, pharmacists, dieticians, diabetes
      educators, laboratory staff, quality management staff, and others. The role of
      pharmacists in this multidisciplinary team is to assist in the standardization of
      insulin therapy via selection of appropriate insulin treatment protocols,
      participate in formulary management of insulin products, and contribute to the
      development of order sets and policies and procedures to minimize the risk of
      medication errors and misadventures. In addition, pharmacists can provide
      guidelines or treatment recommendations in special situations, such as those
      involving patients receiving enteral or parenteral nutrition or high-dose
      corticosteroids and the transition from i.v. to subcutaneous insulin therapy.
      Education of patients and providers is another key role for pharmacists. Nurses
      are important allies in the effort to ensure safe insulin use, as they are at the
      bedside of patients administering and adjusting insulin therapy. Recommendations
      are provided for the safe and effective use of insulin for the treatment of
      inpatient hyperglycemia. CONCLUSION: Pharmacists are an integral part of the
      multidisciplinary team ensuring the safe and effective implementation of
      inpatient hyperglycemic control and insulin usage.

PMID- 20689153
TI  - Cognitive defusion versus thought distraction: a clinical rationale, training,
      and experiential exercise in altering psychological impacts of negative self
      referential thoughts.
AB  - Using two modes of intervention delivery, the present study compared the effects
      of a cognitive defusion strategy with a thought distraction strategy on the
      emotional discomfort and believability of negative self-referential thoughts. One
      mode of intervention delivery consisted of a clinical rationale and training
      (i.e., Partial condition). The other mode contained a condition-specific
      experiential exercise with the negative self-referential thought in addition to
      the clinical rationale and training (i.e., Full condition). Nonclinical
      undergraduates were randomly assigned to one of five protocols: Partial-Defusion,
      Full-Defusion, Partial-Distraction, Full-Distraction, and a distraction-based
      experimental control task. The Full-Defusion condition reduced the emotional
      discomfort and believability of negative self-referential thoughts significantly
      more than other comparison conditions. The positive results of the Full-Defusion
      condition were also found among participants with elevated depressive symptoms.

PMID- 20689154
TI  - The sleep-feeding conflict: Understanding behavioral integration through genetic
      analysis in Drosophila.
AB  - One of the brain's most important functions is the control of homeostatically
      regulated behaviors. Dysregulation of the neural systems controlling sleep and
      feeding underlies many chronic illnesses. In a recent study published in Current
      Biology we showed that flies, like mammals, suppress sleep when starved and
      identified the genes Clock and cycle as regulators of sleep during starvation.
      Here we show that starvation specifically disrupts sleep initiation without
      affecting sleep consolidation. The identification of genes regulating sleep
      feeding interactions will provide insight into how the brain integrates and
      controls the expression of complex behaviors.

PMID- 20689155
TI  - P66SHC and ageing: ROS and TOR?
AB  - Both Reactive Oxygen Species (ROS) and hyperactivation of the nutrient-sensing
      mTOR/S6 kinase cascade have been linked to aging and age-related diseases as well
      as to the anti-aging effect of calorie restriction. Recent findings that the pro
      aging and pro-oxidant molecule p66shc contributes to S6K activation by nutrients
      and promotes insulin resistance and diabetes in mice may provide an answer to the
      "ROS or TOR?" dilemma.

PMID- 20689157
TI  - Adult Drosophila melanogaster as a model for the study of glucose homeostasis.
AB  - Genetic ablation of Drosophila melanogaster insulin-like peptide (DILP) and
      adipokinetic hormone-producing cells accompanied by cell biological and metabolic
      measurements have revealed functional conservation in nutrient sensing and the
      underlying signaling mechanisms between mammal and fruit fly. Despite significant
      advances gained in understanding the neuroendocrine responses to nutrient changes
      during developmental larval stages, we discuss here the need for investigating
      glucose homeostasis in the post-mitotic adult stage as the result of ablation of
      DILP producing cells (IPCs). Our recent studies demonstrate that while both
      constitutive and adult-specific partial ablation of IPCs renders those flies
      hyperglycemic and glucose intolerant, flies with adult-specific IPC ablation
      remain insulin sensitive. Our results substantiate a role of adult IPCs in
      modulating aspects of glucose homeostasis and highlight the complexity in DILP
      action in the adult fly.

PMID- 20689158
TI  - Mimicking honeybee eyes with a 280 degrees field of view catadioptric imaging
      system.
AB  - We present a small single camera imaging system that provides a continuous 280
      degrees field of view (FOV) inspired by the large FOV of insect eyes. This is
      achieved by combining a curved reflective surface that is machined into acrylic
      glass with lenses covering the frontal field that otherwise would have been
      obstructed by the mirror. Based on the work of Seidl (1982 PhD Thesis Technische
      Hochschule Darmstadt), we describe an extension of the 'bee eye optics
      simulation' (BEOS) model by Giger (1996 PhD Thesis Australian National
      University) to the full FOV which enables us to remap camera images according to
      the spatial resolution of honeybee eyes. This model is also useful for simulating
      the visual input of a bee-like agent in a virtual environment. The imaging system
      in combination with our bee eye model can serve as a tool for assessing the
      visual world from a bee's perspective which is particularly helpful for
      experimental setups. It is also well suited for mobile robots, in particular on
      flying vehicles that need light-weight sensors.

PMID- 20689156
TI  - Controlling SIRT1 expression by microRNAs in health and metabolic disease.
AB  - SIRT1 is a NAD+-dependent deacetylase implicated in longevity and diverse
      physiological processes. SIRT1, as a key mediator of beneficial effects of
      caloric restriction, regulates lipid and glucose metabolism by deacetylating
      metabolic regulators, as well as histones, in response to nutritional
      deprivation. Here we discuss how SIRT1 levels are regulated by microRNAs (miRs)
      which are emerging as important metabolic regulators; the recently identified
      nuclear receptor FXR/SHP cascade pathway that controls the expression of miR-34a
      and its target SIRT1; and a FXR/SIRT1 positive feedback regulatory loop, which is
      deregulated in metabolic disease states. The FXR/miR-34a pathway and other miRs
      controlling SIRT1 may be useful therapeutic targets for age-related diseases,
      including metabolic disorders.

PMID- 20689159
TI  - Optical properties of indium phosphide nanowire ensembles at various
      temperatures.
AB  - Ensembles that contain two types (zincblende and wurtzite) of indium phosphide
      nanowires grown on non-single crystalline surfaces were studied by micro
      photoluminescence and micro-Raman spectroscopy at various low temperatures. The
      obtained spectra are discussed with the emphasis on the effects of differing
      lattice types, geometries, and crystallographic orientations present within an
      ensemble of nanowires grown on non-single crystalline surfaces. In the
      photoluminescence spectra, a typical Varshni dependence of band gap energy on
      temperature was observed for emissions from zincblende nanowires and in the high
      temperature regime energy transfer from excitonic transitions and band-edge
      transitions was identified. In contrast, the photoluminescence emissions
      associated with wurtzite nanowires were rather insensitive to temperature. Raman
      spectra were collected simultaneously from zincblende and wurtzite nanowires
      coexisting in an ensemble. Raman peaks of the wurtzite nanowires are interpreted
      as those related to the zincblende nanowires by a folding of the phonon
      dispersion.

PMID- 20689161
TI  - Tunable nanoswitches based on nanoparticle meta-molecules.
AB  - We introduce ultra-fast tunable nanoswitches based on the transition between
      states of nanoparticle meta-molecules. These molecules are formed (activated)
      when hybrid systems consisting of metallic nanoparticles and semiconductor
      quantum dots interact with coherent light sources (laser fields). The switching
      process occurs via minuscule changes of the refractive index of the environment
      or the distance between the quantum dots and metallic nanoparticles. These
      changes stimulate the transition between the states of the meta-molecules in
      nanosecond timescales, setting up dramatic optical events that can be observed
      easily. These nanoswitches can be tuned by varying the intensity of the
      activating laser field, allowing us to adjust the switching process to occur at
      different values of refractive indices. The results open a new horizon for
      chemically, biologically, or physically triggered optical nanoswitches and
      nanosensors that are sensitive to ultra-small changes in the environment.

PMID- 20689162
TI  - Sustained ferromagnetism induced by H-vacancies in graphane.
AB  - The electronic and magnetic properties of graphane flakes with H-vacancies were
      investigated using quantum-chemistry methods. The hybridization of the edges is
      found to be absolutely crucial in defining the size of the HOMO-LUMO gap, which
      is increased from 3.04 to 7.51 eV when the hybridization is changed from the
      sp(2) to the sp(3) type. The H-vacancy defects also influence the size of the
      gap, which depends on the number of defects and their distribution between the
      two sides of the graphane plane. Further, the H-vacancy defects induced on one
      side of the graphane plane and placed on the neighboring carbon atoms are found
      to be the source of ferromagnetism which is distinguished by the high stability
      of the state with a large spin number in comparison to that of the singlet state
      and is expected to persist even at room temperatures. However, the ferromagnetic
      ordering of the spins is found to be limited by the concentration of H-vacancy
      defects and ordering would be preserved if number of defects does not exceed
      eight.

PMID- 20689163
TI  - Comment on 'Model calculation of the scanned field enhancement factor of CNTs'.
AB  - The model proposed by Ahmad and Tripathi (2006 Nanotechnology 17 3798)
      demonstrates that the field enhancement factor of carbon nanotubes (CNTs) reaches
      a maximum at a certain length. Here, we show that this behavior should not occur
      and suggest our correction to this model.

PMID- 20689164
TI  - Characterization of endocytosis and exocytosis of cationic nanoparticles in
      airway epithelium cells.
AB  - A major challenge of drug delivery using colloids via the airway is to understand
      the mechanism implied in their interactions with epithelial cells. The purpose of
      this work was to characterize the process of endocytosis and exocytosis of
      cationic nanoparticles (NPs) made of maltodextrin which were developed as a
      delivery system for antigens in vaccine applications. Confocal microscopy
      demonstrated that these NP are rapidly endocytosed after as little as 3 min
      incubation, and that the endocytosis was also faster than NP binding since most
      of the NPs were found in the middle of the cells around the nuclei. A saturation
      limit was observed after a 40 min incubation, probably due to an equilibrium
      becoming established between endocytosis and exocytosis. Endocytosis was
      dramatically reduced at 4 degrees C compared with 37 degrees C, or by NaN(3)
      treatment, both results suggesting an energy dependent process. Protamine
      pretreatment of the cells inhibited NPs uptake and we found that clathrin pathway
      is implied in their endocytosis. Cholesterol depletion increased NP uptake by
      300% and this phenomenon was explained by the fact that cholesterol depletion
      totally blocked NP exocytosis. These results suggest that these cationic NPs
      interact with anionic sites, are quickly endocytosed via the clathrin pathway and
      that their exocytosis is cholesterol dependent, and are similar to those obtained
      in other studies with viruses such as influenza.

PMID- 20689165
TI  - Self-assembled copolymeric nanoparticles as chemically interactive materials for
      humidity sensors.
AB  - Chemical interactive materials (CIM), based on poly(methylmethacrylate-co
      bis(benzocyclobutene)) P(MMA-co-BCB) and poly(styrene-co-bis(benzocyclobutene))
      P(S-co-BCB) nanoparticles, have been prepared through modified emulsion
      technique. Experimental conditions, in particular the co-monomer ratio and
      reaction time, have been tuned to modulate nanoparticles' dimension and optimize
      their monodispersity. Resistive relative humidity (RH) sensors based on self
      assembled copolymeric nanoparticles, cast deposited onto metal interdigitated
      electrodes (Al, Au, Cr), have been fabricated. The electrical response and the
      devices' stability have been studied in the range 10-90% RH. Applying 1 V to
      interdigitated electrodes, a variation of four orders of magnitude, from 10(-12)
      to 10(-8) A, has been observed and a response time of 130 s has been calculated.
      Response reproducibility and stability have been tested in subsequent cycles of
      measurements (working times as long as two days and after six months), confirming
      the stable performance of the CIMs. Copolymeric nanoparticle assembly has also
      been studied by quartz microbalance (QMB) devices, where phase shift occurred, by
      varying RH in the range 10-90%. The CIM coated device shows a sensitivity of
      about 30 Hz/% (at 10-70% RH), that rapidly increases up to about 2000 Hz/% at 90%
      RH. The results give evidence for versatile applications of P(MMA-co-BCB) and P(S
      co-BCB) nanoparticles for sensing applications.

PMID- 20689166
TI  - Spin interactions in a quantum dot containing a magnetic impurity.
AB  - The electron and hole states in a CdTe quantum dot containing a single magnetic
      impurity in an external magnetic field are investigated using a multiband
      approximation which includes the heavy hole-light hole coupling effects. The
      electron-hole spin interactions and sp-d interactions between the electron, the
      hole and the magnetic impurity are also included. The exciton energy levels and
      optical transitions are evaluated using the exact diagonalization scheme. A novel
      mechanism is proposed here to manipulate impurity spin in the quantum dot which
      allows us to drive selectively the spin of the magnetic atom into each of its six
      possible orientations.

PMID- 20689167
TI  - A self-assembled multimodal complex for combined pre- and intraoperative imaging
      of the sentinel lymph node.
AB  - Specific removal of the sentinel lymph node (SLN) during breast cancer surgery
      presents physicians with the opportunity to detect early metastatic disease. To
      increase the accuracy of intraoperative SLN detection, new methods with higher
      sensitivity and specificity are required. We have quantitatively compared
      conventional preoperative lymphoscintigraphy with albumin radiocolloids ((99m)Tc
      NanoColl) with optical intraoperative guidance using the near infrared dye
      indocyanine green (ICG) in an orthotopic mouse model for metastatic breast
      cancer. Furthermore, we have applied a self-assembled multimodal complex, in
      which ICG is non-covalently bound to the albumin radiocolloid, to attain
      identical dynamics of the radioactive and optical components. The SLN specificity
      of the multimodal complex is similar to conventional lymphoscintigraphy, while
      the fluorescent signal-to-noise ratio is improved by 86% compared to ICG alone.
      In addition, the multimodal complex permits scintigraphic validation of the
      fluorescent findings. The multimodal ICG-(99m)Tc-NanoColl complex can be used
      both for lymphoscintigraphy by preoperative single photon emission computed
      tomography/computed tomography and for surgical navigation by intraoperative
      fluorescence imaging.

PMID- 20689168
TI  - The fabrication of a patterned ZnO nanorod array for high brightness LEDs.
AB  - In this study, a patterned ZnO nanorod array was formed on the ITO layer of GaN
      based light-emitting diodes (LEDs), to increase the light extraction efficiency
      of the LED. The bi-layer imprinted resin pattern was used for selective growth of
      the ZnO nanorod array on the ITO layer. Compared to conventional LEDs grown on
      patterned sapphire substrate (PSS), the deposition of the blanket ZnO layer on
      the ITO layer increased the light extraction efficiency of the LED by about 10%.
      Further growth of the ZnO nanorod layer on the blanket ZnO layer increased the
      light extraction efficiency of the LED by about 23%. In the case that a patterned
      ZnO nanorod layer was formed on a blanket ZnO layer, the light extraction
      efficiency increased by about 34%. These enhancements of the device were caused
      by modulation of the refractive-index in ZnO layers and the surface roughening
      effects because of the unique design of the pattern, which was nanostructure-in
      nanopattern, resulting in the formation of many escape cones on the LED surface.

PMID- 20689169
TI  - In situ real-time monitoring of changes in the surface roughness during
      nonadiabatic optical near-field etching.
AB  - We performed in situ real-time monitoring of the change in surface roughness
      during self-organized optical near-field etching. During near-field etching of a
      silica substrate, we detected the scattered light intensity from a continuum wave
      (CW) laser (lambda = 633 nm) in addition to the etching CW laser (lambda = 532
      nm) light source. We discovered that near-field etching not only decreases
      surface roughness, but also increases the number of scatterers, as was confirmed
      by analyzing the AFM image. These approaches provide optimization criteria for
      the etching parameter and hence for further decreases in surface roughness.

PMID- 20689170
TI  - Heat shock protein 90: a capacitor or a mutator?

PMID- 20689171
TI  - The small subunit of geranyl diphosphate synthase: a tool to improve aroma and
      flavour by metabolic engineering.

PMID- 20689172
TI  - Wolbachia and termite association: present status and future implications.

PMID- 20689173
TI  - What history tells us XXI. Apoptosis and programmed cell death: when biological
      categories are blurred.

PMID- 20689174
TI  - The light of the firefly under the influence of ethyl acetate.
AB  - When a firefly is made to inhale ethyl acetate vapour, a constant glow appears
      after a few minutes from its abdominal lantern. This control experiment has been
      performed by a few workers to record the emission spectrum of the firefly.
      However, a time-resolved experiment performed by us on this continuous light
      emitted by the species Luciola praeusta Kiesenwetter 1874 (Coleoptera :
      Lampyridae : Luciolinae) reveals that it is composed of a continuous train of
      tiny pulses! The nature of the pulses suggests that an oscillatory chemical
      reaction continues in the microsecond time scale in the lantern of the
      anaesthetized firefly.

PMID- 20689176
TI  - Tumour bed irradiation of human tumour xenografts in a nude rat model using a
      common X-ray tube.
AB  - Studies that investigate the radiation of human tumour xenografts require an
      appropriate radiation source and highly standardized conditions during radiation.
      This work reports on the design of a standardized irradiation device using a
      commercially available X-ray tube with a custom constructed lead collimator with
      two circular apertures and an animal bed plate, permitting synchronous
      irradiation of two animals. Dosimetry and the corresponding methodology for
      radiotherapy of human non-small cell lung cancer xenograft tumours transplanted
      to and growing subcutaneously on the right lower limb in a nude rat model were
      investigated. Procedures and results described herein prove the feasibility of
      use of the device, which is applicable for any investigation involving
      irradiation of non-tumorous and tumorous lesions in small animals.

PMID- 20689175
TI  - Spectrum of CREBBP mutations in Indian patients with Rubinstein-Taybi syndrome.
AB  - Rubinstein-Taybi syndrome (RSTS), a developmental disorder comprising
      abnormalities that include mental retardation, an unusual facial appearance,
      broad thumbs and big toes is frequently associated with molecular lesions in the
      CREB-binding protein gene, CREBBP. The objective of the present study was to
      identify and analyse CREBBP mutations in Indian RSTS patients on which there are
      no data. Direct sequencing of CREBBP performed in 13 RSTS patients identified the
      three zinc fingers (CH1, CH2, CH3) and HAT domain as mutational hotspots in which
      ten novel pathogenic mutations were localized. Functional analysis revealed that
      three of these mutations affecting amino acids Glu1459, Leu1668 and Glu1724 were
      critical for histone acetyltransferase activity. Twenty-eight novel CREBBP single
      nucleotide polymorphisms (SNPs) were also identified in the Indian population.
      Linkage disequilibrium studies revealed associations between (i) SNP
      (rs129974/c.3836-206G greater than C) and mutation (p.Asp1340Ala); (ii)
      (rs130002) with mutation (p.Asn435Lys) and (iii) SNPs rs129974, rs130002 and SNP
      (c.3836-206G greater than C) signifying a disease affection status. In
      conclusion, the present study reports the highest detection rate of CREBBP
      mutations (76.9%) in RSTS patients to date, of which ten are predicted to be
      pathogenic and three critical for histone acetyltransferase activity. Moreover,
      identification of the association of CREBBP polymorphisms with disease
      susceptibility could be an important risk factor for the pathogenesis of RSTS.

PMID- 20689178
TI  - Activated charcoal filter effectively reduces p-benzosemiquinone from the
      mainstream cigarette smoke and prevents emphysema.
AB  - In this paper, we have made a comparative evaluation of the cytotoxicity and
      pathophysiological effects of mainstream smoke from cellulose acetate (CA)
      filtered cigarettes with that of charcoal-filtered cigarettes developed in our
      laboratory. Previously, we had demonstrated that the mainstream smoke from an
      Indian CA-filtered commercial cigarette contains p-benzosemiquinone (p-BSQ), a
      major, highly toxic, long-lived water-soluble radical. Here, we have examined 16
      brands of different CA-filtered cigarettes including Kentucky research
      cigarettes, and observed that mainstream smoke from all the cigarettes contains
      substantial amounts of p-BSQ (100-200 MUg/cigarette). We also show that when the
      CA filter is replaced by a charcoal filter, the amount of p-BSQ in the mainstream
      smoke is reduced by 73-80%, which is accompanied by a reduction of carbonyl
      formation in bovine serum albumin to the extent of 70- 90%. The charcoal filter
      also prevented cytotoxicity in A549 cells as evidenced by MTT assay, apoptosis as
      evidenced by FACS analysis, TUNEL assay, overexpression of Bax, activation of p53
      and caspase 3, as well as emphysematous lung damage in a guinea pig model as seen
      by histology and morphometric analysis. The results indicate that the charcoal
      filter developed in our laboratory may protect smokers from cigarette smoke
      induced cytotoxity, protein modification, apoptosis and emphysema.

PMID- 20689177
TI  - Inhibition of human lung adenocarcinoma growth using survivint34a by low-dose
      systematic administration.
AB  - Anti-apoptosis plays an important role in tumour formation and development.
      Survivin is a member of the inhibitor of apoptosis (IAP) family, which is a
      target for anti-cancer drug exploitation was replaced as development. We
      investigated the role of the homo dominant-negative mutant Survivin-T34A in
      suppressing human lung adenocarcinomas (A549). The anti-tumour activity of
      HSurvivinT34A plasmid was evaluated in the A549 cell line and nude mice bearing
      A549 subcutaneous tumours. Low-dose systemic administration was continuously
      used. The HSurvivinT34A plasmid (5 meu g/one) complexed with a cationic liposome
      (DOTAP/Chol) significantly inhibited tumour growth in our model. We observed
      microvessel density degradation by CD31 immunohistochemistry and apoptotic cell
      increase by TUNEL assay, PI staining and flow cytometric analysis in the treated
      group. The present findings suggest that the HSurvivinT34A plasmid complexed with
      a cationic liposome may provide an effective approach to inhibit the growth of
      human lung adenocarcinomas in vitro and in vivo.

PMID- 20689179
TI  - Antimicrobial, antioxidant, cytotoxicity and platelet aggregation inhibitory
      activity of a novel molecule isolated and characterized from mango ginger
      (Curcuma amada Roxb.) rhizome.
AB  - Mango ginger (Curcuma amada Roxb.) rhizome is used in the manufacture of pickles
      and other food preparations due to its unique raw mango flavour. The chloroform
      extract of mango ginger rhizome was subjected to antibacterial activity-guided
      purification by repeated silica gel column chromatography to obtain a pure
      compound. The structure of the isolated compound was deduced by analysing UV, IR,
      LC-MS and 2D-HMQCT NMR spectral data, and named it as amadaldehyde, a novel
      compound. It exhibited a wide range of antibacterial activity with potential
      bactericidal activity against several bacteria. The purified compound also
      exhibited antioxidant activity, cytotoxicity and platelet aggregation inhibitory
      activities.

PMID- 20689181
TI  - Morphological changes in the cephalic salivary glands of females and males of
      Apis mellifera and Scaptotrigona postica (Hymenoptera, Apidae).
AB  - The cephalic salivary glands of some species of bees are exclusive and well
      developed only in Apinae. These glands were studied with light and scanning
      electron microscopy in workers, queens and males from the honey bee Apis
      mellifera, and the stingless bee Scaptotrigona postica in different life phases.
      The results show that the cephalic salivary glands are present in females of both
      the species, and in males of S. postica. Nevertheless, they are poorly developed
      in young males of A. mellifera. In both species, gland growth is progressive from
      the time of emergence to the oldest age but, in A. mellifera males, the gland
      degenerates with age. Scanning electron microscopy shows that the secretory units
      of newly emerged workers are collapsed while in older workers they are turgid.
      Some pits on the surface of the secretory units correspond to open intercellular
      spaces. The possible functions of these glands in females and males of both
      species are discussed.

PMID- 20689180
TI  - Characterization of Helicobacter pylori adhesin thiol peroxidase (HP0390)
      purified from Escherichia coli.
AB  - The antioxidant protein, adhesin thiol peroxidase (HpTpx or HP0390), plays an
      important role in enabling Helicobacter pylori to survive gastric oxidative
      stress. The bacterium colonizes the host stomach and produces gastric cancer.
      However, little information is available about the biochemical characteristics of
      HpTpx. We expressed recombinant HpTpx in Escherichia coli, purified to
      homogeneity, and characterized it. The results showed that HpTpx existed in a
      monomeric hydrodynamic form and the enzyme fully retained its peroxidase and
      antioxidant activities. The catalytic reaction of the enzyme was similar to an
      atypical 2-cysteine peroxiredoxin (Prx). The conformation of the enzyme was
      observed in the presence and absence of dithiothreitol (DTT); similar to other
      known thiol peroxidases, conformational change was observed in HpTpx by the
      addition of DTT.

PMID- 20689182
TI  - Unusual allometry for sexual size dimorphism in a cichlid where males are
      extremely larger than females.
AB  - When males are the larger sex, a positive allometric relationship between male
      and female sizes is often found across populations of a single species (i.e.
      Rensch's rule). This pattern is typically explained by a sexual selection
      pressure on males. Here, we report that the allometric relationship was negative
      across populations of a shell-brooding cichlid fish Lamprologus callipterus,
      although males are extremely larger than females. Male L. callipterus collect and
      defend empty snail shells in each of which a female breeds. We found that, across
      six populations, male and female sizes are positively correlated with not only
      sexual and fecundity selection indices, but also with shell sizes. Given their
      different reproductive behaviours, these correlations mean that males are
      required to be more powerful, and thus larger, to transport larger shells, while
      female bodies are reduced to the shell size to enable them to enter the shells.
      Among the three size selections (sexual selection, fecundity selection and shell
      size), shell size explained the allometry, suggesting that females are more
      strongly subject to size selection associated with shell size availability than
      males. However, the allometry was violated when considering an additional
      population where size-selection regimes of males differed from that of other
      populations. Therefore, sexual size allometry will be violated by body size
      divergence induced by multiple selection regimes.

PMID- 20689183
TI  - Genetic and clonal diversity of the endemic ant-plant Humboldtia brunonis
      (Fabaceae) in the Western Ghats of India.
AB  - Humboldtia brunonis (Fabaceae, Caesalpinioideae) is a dominant self-incompatible
      ant-plant or myrmecophyte, growing as an understorey tree in high-density
      patches. It is endemic to the biodiversity hotspot of the southern Western Ghats
      of India and, besides ants, harbours many endemic invertebrate taxa, such as bees
      that pollinate it as well as arboreal earthworms, within swollen hollow stem
      internodes called domatia. Using inter simple sequence repeat (ISSR) markers,
      three geographically separated populations were found to be multiclonal,
      characterized by high levels of clonal diversity. Values for the Simpson
      diversity index ranged between 0.764 and 0.964, and for Fager's evenness index
      between 0.00 and 0.036 for neighbourhoods within populations. This myrmecophyte
      was found to combine sexual recruitment (66.7%) and clonal production (33.3%) as
      methods of reproduction. Moderate amounts of genetic diversity at the species
      level were observed, with 52.63% polymorphism, and moderate values of Shannon's
      diversity index (0.1895) as well as of Nei's gene diversity (0.1186). In each
      population, observed genotypic diversity was significantly lower than expected,
      indicating significant genetic structure. Neighbour-joining trees demonstrated
      that Agumbe, which is the most northern population examined and geographically
      twice as far away from the other two populations, grouped separately and with
      larger bootstrap support from a larger cluster consisting of the Sampaji and
      Solaikolli populations, which are closer to each other geographically. Some
      neighbourhoods within each population showed spatial genetic structure even at
      small spatial scales of less than 5 m. A combination of clonality and short
      distance pollen movement by small pollinating bees (Braunsapis puangensis)
      coupled with primary ballistic seed dispersal, and possible secondary seed
      dispersal by rodents, may contribute to spatial genetic structure at such small
      scales. The clonality of H. brunonis may be a factor that contributes to its
      dominance in Western Ghat forests where it supports a rich diversity of
      invertebrate fauna.

PMID- 20689184
TI  - An insight into the sequential, structural and phylogenetic properties of banana
      1-aminocyclopropane-1-carboxylate synthase 1 and study of its interaction with
      pyridoxal-5'-phosphate and aminoethoxyvinylglycine.
AB  - In banana, ethylene production for ripening is accompanied by a dramatic increase
      in 1-aminocyclopropane-1-carboxylate (ACC) content, transcript level of Musa
      acuminata ACC synthase 1 (MA-ACS1) and the enzymatic activity of ACC synthase 1
      at the onset of the climacteric period. MA-ACS1 catalyses the conversion of S
      adenosyl-L-methionine (SAM) to ACC, the key regulatory step in ethylene
      biosynthesis. Multiple sequence alignments of 1-aminocyclopropane-1-carboxylate
      synthase (ACS) amino acid sequences based on database searches have indicated
      that MA-ACS1 is a highly conserved protein across the plant kingdom. This report
      describes an in silico analysis to provide the first important insightful
      information about the sequential, structural and phylogenetic characteristics of
      MA-ACS1. The three-dimensional structure of MA-ACS1, constructed based on
      homology modelling, in combination with the available data enabled a comparative
      mechanistic analysis of MA-ACS1 to explain the catalytic roles of the conserved
      and non-conserved active site residues. We have further demonstrated that, as in
      apple and tomato, banana- ACS1 (MA-ACS1) forms a homodimer and a complex with
      cofactor pyridoxal-5'-phosphate (PLP) and inhibitor aminoethoxyvinylglycine
      (AVG). We have also predicted that the residues from the PLP-binding pocket,
      essential for ligand binding, are mostly conserved across the MA-ACS1 structure
      and the competitive inhibitor AVG binds at a location adjacent to PLP.

PMID- 20689185
TI  - Aligning protein sequence and analysing substitution pattern using a class
      specific matrix.
AB  - Aligning protein sequences using a score matrix has became a routine but valuable
      method in modern biological research. However, alignment in the 'twilight zone'
      remains an open issue. It is feasible and necessary to construct a new score
      matrix as more protein structures are resolved. Three structural class-specific
      score matrices (all-alpha, all-beta and alpha/beta) were constructed based on the
      structure alignment of low identity proteins of the corresponding structural
      classes. The class-specific score matrices were significantly better than a
      structure-derived matrix (HSDM) and three other generalized matrices (BLOSUM30,
      BLOSUM60 and Gonnet250) in alignment performance tests. The optimized gap
      penalties presented here also promote alignment performance. The results indicate
      that different protein classes have distinct amino acid substitution patterns,
      and an amino acid score matrix should be constructed based on different
      structural classes. The class-specific score matrices could also be used in
      profile construction to improve homology detection.

PMID- 20689186
TI  - Nuclear reprogramming and epigenetic rejuvenation.

PMID- 20689187
TI  - The conversion of spring wheat into winter wheat and vice versa: false claim or
      Lamarckian inheritance?

PMID- 20689188
TI  - The significance of case reports in biomedical publication.

PMID- 20689189
TI  - Evaluation of Ahmed glaucoma valve implantation through a needle-generated
      scleral tunnel in Mexican children with glaucoma.
AB  - PURPOSE: To evaluate the results and extrusion rates of the Ahmed glaucoma valve
      (AGV) implantation through a needle-generated scleral tunnel, without a tube
      covering patch, in children. MATERIALS AND METHODS: A retrospective review of the
      charts of 106 Mexican children implanted with 128 AGVs operated between 1994 and
      2002, with the needle track technique, at our institution, with at least six
      months follow up was done. Main outcome measures were intraocular pressure (IOP)
      control, tube extrusions or exposure and other complications. RESULTS: Kaplan
      Meier analysis demonstrated a 96.9% survival rate at six months, 82.4% at one
      year, 78.7% at two years, 70% at three years and 41.6% at four years. Total
      success at the last follow-up (IOP between 6 and 21 mm Hg without medications)
      was achieved in 30 eyes (23.5%), 58 eyes (45.3%) had qualified success (only
      topical hypotensive drugs) and 40 eyes (31.3%) were failures. The mean pre- and
      post-operative IOP at the last follow up was 28.4 mmHg (SD 9.3) and 14.5 mmHg (SD
      6.3), respectively. No tube extrusions or exposures were observed. Tube-related
      complications included five retractions, a lens touch and a transitory
      endothelial touch. The risk of failure increased if the eye had any complication
      or previous glaucoma surgeries. CONCLUSION: Medium-term IOP control in Mexican
      children with glaucoma can be achieved with AGV implantation using a needle
      generated tunnel, without constructing a scleral flap or using a patch to cover
      the tube. There were no tube extrusions, nor any tube exposures with this
      technique.

PMID- 20689190
TI  - Increased levels of vascular endothelial growth factor in the aqueous humor of
      patients with diabetic retinopathy.
AB  - PURPOSE: This study aims to investigate the levels of aqueous vascular
      endothelial growth factor (VEGF) in diabetic patient groups in comparison to
      normal subjects, and to correlate elevated VEGF with the severity of diabetic
      retinopathy (DR). MATERIALS AND METHODS: Aqueous samples were obtained from 78
      eyes of 74 patients undergoing intraocular surgery and they were examined by the
      enzyme-linked immunosorbent assay. Color photographs, optical coherence
      tomography scans, and fluorescein angiography were used to evaluate patients
      preoperatively. RESULTS: A strong statistical correlation was found to exist
      between the level of aqueous VEGF and the severity of DR ( P < 0.001), whereas,
      the VEGF levels in a control group and a diabetic group without DR were not
      significantly different ( P = 0.985). Aqueous VEGF levels were significantly
      elevated in patients with proliferative DR (PDR) as compared to the control group
      ( P < 0.001), to diabetic patients without retinopathy (NDR) ( P < 0.001), and to
      diabetic patients with nonproliferative DR (NPDR) ( P < 0.001). The aqueous VEGF
      levels were significantly higher in patients with active PDR than in those with
      quiescent PDR ( P = 0.001). On the other hand, a statistically insignificant ( P
      = 0.065) correlation was found between elevated aqueous VEGF and the presence of
      macular edema in the NPDR group. CONCLUSIONS: VEGF was elevated in the aqueous
      humor of patients with DR compared to that in normal eyes. The aqueous VEGF level
      had a strong correlation with the severity of retinopathy along with a
      statistically insignificant difference in macular edema.

PMID- 20689191
TI  - Comparison of serum glycosylated hemoglobin levels in patients with diabetic
      cystoid macular edema with and without serous macular detachment.
AB  - AIM: A clinical comparative trial was conducted to compare the levels of
      glycosylated hemoglobin (HbA1c) in patients with diabetic cystoid macular edema
      (CME) with and without serous macula detachment (SMD). MATERIALS AND METHODS:
      Thirty patients (group 1) with diabetic CME in both eyes, but without SMD, and 30
      patients (group 2) with diabetic CME and SMD in both eyes documented by optical
      coherence tomography (OCT) and fundus fluorescein angiography (FFA), were
      included in the study. In addition to the measurement of central macular
      thickness by OCT and visual acuity (VA) (as logMAR) using the the early treatment
      diabetic retinopathy study (ETDRS) chart, the concentrations of HbA1c were
      measured by high performance liquid chromatography (HPLC). Statistical analysis
      was done by independent samples t test. RESULTS: The mean logMAR VA was 0.8 +/-
      0.22 (1.0-0.5) in group 1 and 0.7 +/- 0.16 (1.0-0.6) in group 2. The mean central
      macular thickness, as determined by OCT, was 468.70 +/- 70.44 microm (344-602
      microm) in group 1 and 477.80 +/- 73.34 microm (354-612 microm) in group 2. The
      difference between the groups was not statistically significant (P = 0.626). The
      mean HbA1c levels were 8.16 +/- 0.99% in group 1 and 10.05 +/- 1.66% in group 2.
      The difference between the groups was statistically significant (P < 0.001).
      CONCLUSIONS: The presence of SMD and high HbA1c levels in the patients with
      diabetic CME may be indirectly suggestive of retinal pigment epithelium
      dysfunction.

PMID- 20689192
TI  - Comparison of central corneal thickness measurements with the Galilei dual
      Scheimpflug analyzer and ultrasound pachymetry.
AB  - PURPOSE: To compare corneal pachymetry assessment by the Galilei dual Scheimpflug
      analyzer with that done by ultrasound (US) pachymetry. MATERIALS AND METHODS:
      Forty six patients (92 eyes) were subjected to corneal pachymetry assessment by
      Galilei dual Scheimpflug analyzer and US. All the readings were taken by a single
      operator. Intraoperator repeatability for the Galilei was assessed by taking 10
      readings in one eye each of 10 patients. To study the interoperator
      reproducibility for the Galilei, two observers took a single reading in both the
      eyes of 25 patients. RESULTS: The mean central corneal thickness (CCT) measured
      by US was 541.83 +/- 30.56 microm standard deviation (SD) and that measured by
      Galilei was 541.27 +/- 30.07 microm (SD). There was no statistically significant
      difference between both the methods (P < 0.001). The coefficient of repeatability
      was 0.43% while the coefficient of reproducibility was 0.377% for the Galilei.
      CONCLUSION: Objective, noncontact measurement of the CCT with the Galilei dual
      Scheimpflug analyzer was convenient, had excellent intraoperator repeatability
      and interoperator reproducibility, and findings were similar to those obtained
      with standard US pachymetry.

PMID- 20689193
TI  - Effect of cataract surgery on retinal nerve fiber layer thickness parameters
      using scanning laser polarimetry (GDxVCC).
AB  - PURPOSE: To study the effect of cataract extraction on the retinal nerve fiber
      layer (RNFL) thickness, and assessment by scanning laser polarimetry (SLP), with
      variable corneal compensation (GDx VCC), at the glaucoma service of a tertiary
      care center in North India. MATERIALS AND METHODS: Thirty-two eyes of 32 subjects
      were enrolled in the study. The subjects underwent RNFL analysis by SLP (GDx VCC)
      before undergoing phacoemulsification cataract extraction with intraocular lens
      (IOL) implantation (Acrysof SA 60 AT) four weeks following cataract surgery. The
      RNFL thickness parameters evaluated both before and after surgery included
      temporal, superior, nasal, inferior, temporal (TSNIT) average, superior average,
      inferior average, and nerve fiber index (NFI). RESULTS: The mean age of subjects
      was 57.6 +/- 11.7 years (18 males, 14 females). Mean TSNIT average thickness
      (microm) pre- and post-cataract surgery was 49.2 +/- 14.1 and 56.5 +/- 7.6 ( P =
      0.001). There was a statistically significant increase in RNFL thickness
      parameters (TSNIT average, superior average, and inferior average) and decrease
      in NFI post-cataract surgery as compared to the baseline values. Mean NFI pre-
      and post-cataract surgery was 41.3 +/- 15.3 and 21.6 +/- 11.8 ( P = 0.001).
      CONCLUSIONS: Measurement of RNFL thickness parameters by scanning laser
      polarimetry is significantly altered following cataract surgery. Post the
      cataract surgery, a new baseline needs to be established for assessing the
      longitudinal follow-up of a glaucoma patient. The presence of cataract may lead
      to an underestimation of the RNFL thickness, and this should be taken into
      account when analyzing progression in a glaucoma patient.

PMID- 20689194
TI  - Cut and paste: a novel method of re-attaching rectus muscles with cyanoacrylate
      during recessions in strabismus.
AB  - AIM: Bio-adhesives like cyanoacrylate offer an alternative to sutures to attach
      tissues, including in ophthalmology. This prospective trial evaluated the
      suitability and bio-tolerance of iso-amyl cyanoacrylate in rectus muscle
      recession surgery for strabismus. MATERIALS AND METHODS: We randomized one eye in
      each of 10 cases of bilateral horizontal rectus recessions to 6/0 polyglactin and
      the other to iso-amyl-cyanoacrylate. We compared time to reattachment (from
      disinsertion), complications and inflammatory scores (0 to +3: nil, mild,
      moderate and severe) on Day One, at two and at four to six weeks post surgery.
      RESULTS: There were no significant group differences in inflammatory scores
      (Wilcoxon, all values of P>0.05). All attachments held firm. Gluing took
      significantly longer by 5.24+/-1.91 min (95% CI for difference: 3.87-6.61). There
      were no complications. CONCLUSION: We feel that although it takes marginally
      longer, iso-amyl cyanoacrylate offers an effective and safe alternative to
      sutures for muscle recession in strabismus surgery. Since it is cheaper (vs.
      polyglactin) and offers multi-use possibility it may also prove to be cost
      effective.

PMID- 20689195
TI  - Clinical features, management and visual outcome of polypoidal choroidal
      vasculopathy in Indian patients.
AB  - AIMS: To present the clinical, indocyanine green angiography (ICGA) features and
      results of treatment for polypoidal choroidal vasculopathy (PCV) in Indian
      patients by a retrospective chart review. MATERIALS AND METHODS: Forty five
      patients with PCV underwent complete ocular examination, fluorescein angiography
      (FFA) and ICGA. Treatment was advised for patients with macular involvement and
      progressive loss of visual acuity. Demographic data, clinical features and
      results of treatment were analyzed. RESULTS: Mean age at presentation was 61.06
      years. Mean follow up was 18 months. The disease was more prevalent in males.
      Forty three patients had unilateral disease. The most common location of polyps
      in ICGA was subfoveal (42.5%). Exudative form was seen in 34 of the 47 eyes and
      the remaining 13 eyes had a hemorrhagic presentation. Thirty four eyes underwent
      treatment which included thermal laser (n = 11), photodynamic therapy (PDT) (n =
      11) and transpupillary thermo therapy (TTT) (n = 12). Statistical analysis was
      done using the Chi-square test. Subgroup analysis of visual outcome following
      various modalities of treatment showed that the results of PDT (P < 0.001) and
      thermal laser (P < 0.001) were statistically significant. CONCLUSIONS: PCV is an
      important differential diagnosis in patients presenting with serosanginous
      maculopathy and submacular hemorrhage. The disease was more prevalent in males
      and was unilateral in the Indian population. Timely intervention in cases with
      symptomatic polyps could achieve stabilization of visual acuity. Thermal laser
      and PDT were safe and effective.

PMID- 20689196
TI  - Comparison of patient satisfaction with services of vision centers in rural areas
      of Andhra Pradesh, India.
AB  - AIM: To compare the satisfaction of patients with the services of Vision Center
      services (primary eye care) in large village (s) and small village (s) in rural
      settings in Andhra Pradesh state, India. MATERIALS AND METHODS: We have
      administered standard questionnaires to randomly selected patients to assess
      patient satisfaction when assessing Vision Center Services. We used the Chi
      square ( P <0.05) to explore differences in satisfaction of patients with Vision
      Center services located in the large village (s) and small village (s) rural
      settings. RESULTS: Vision Center patients at the large village (s) expressed
      higher levels of satisfaction (median 78%) than patients treated at the Vision
      Center at small village (s) (median 69%). The difference was statistically
      significant (Chi square P value ranging from <0.001 to 0.03) for all the items
      except two - 'easy to identify vision center location' and 'spectacles dispensing
      time' as compared to other (privately run optometry) facilities (Chi square P
      value=0.498 and 0.993 respectively). The location of the Vision Center,
      convenience of journey, ophthalmic technician's behavior with patients, are some
      of the most important factors that determined the patient perception about Vision
      Center services. CONCLUSION: The overall satisfaction levels of the Vision Center
      experience at 78% and 69% were good. However, continual improvement is to be made
      in service time, staff performance, cost and quality of vision care, especially
      at more remote primary eye Care Centers.

PMID- 20689197
TI  - Colletotrichum graminicola keratitis: first case report from India.
AB  - Colletotrichum graminicola is a medically important fungus belonging to the order
      Melanconiales under the class Coelomycetes. The members of the genus
      Colletotrichum are primarily plant pathogens which cause anthracnoses (fungal
      infection in plants). In the past few decades, they are progressively being
      implicated as etiological agents of subcutaneous hyalohyphomycoses and
      keratomycoses. Of the five medically important members in the genus
      Colletotrichum, keratitis due to Colletotrichum graminicola is rare. We diagnosed
      Colletotrichum graminicola keratitis in a 44-year-old man who presented with a
      non-healing corneal ulcer since three weeks. Positive smears and cultures from
      the corneal scrapings established the causative organism as C. graminicola. The
      patient was treated with a combination of oral ketoconazole and topical
      fluconazole and natamycin. Infection resolved over 10 weeks and antimicrobials
      were stopped. We describe the clinical presentation and treatment outcome of
      Colletotrichum graminicola keratitis.

PMID- 20689198
TI  - Measuring normal ocular torsion and its variation by fundus photography in
      children between 5-15 years of age.
AB  - Cycloposition has been measured by various methods; however, fundus photography
      is the most reliable method to evaluate the torsion objectively. We did a
      prospective study to find out the disc foveal angle (DFA) and its variation in
      children without squint. We included 210 eyes of 105 children between the ages of
      5-15 years. DFA was calculated using standard technique after taking a fundus
      photograph. The cycloplegic refraction was done and compared. The mean age was
      10.6 +/- 2.5 years. Mean DFA in right eye (RE) was 6.49 +/- 3.25 degrees (0-13
      degrees ) and in left eye (LE) was 5.80 +/- 3.29 degrees (0-12 degrees ). The
      difference between the RE and LE was statistically not significant (P=0.131)
      (mean 1.15 +/-1.39 degrees ). Mean DFA in emmetropic children was 6.1 degrees +/-
      3.4 degrees (n=112 eyes). DFA varies widely in children. The difference observed
      in DFA measurement for eyes with various refractive errors were compared with DFA
      measurements for emmetropic eyes.

PMID- 20689199
TI  - A case of central retinal artery occlusion following embolization procedure for
      juvenile nasopharyngeal angiofibroma.
AB  - A 23-year-old male patient with right nasal Juvenile Nasopharyngeal Angiofibroma
      (JNA) developed Central Retinal Artery Occlusion (CRAO) during embolization of
      the tumor using polyvinyl alcohol particles before endoscopic excision. Classic
      CRAO management was initiated by an ophthalmologist after 12 h. Retrospective
      evaluation of the angiograms revealed a tiny communication between the external
      carotid and ophthalmic arteries which had not been noticed before embolization.
      During endoscopic excision, the tumor was found to originate extraordinarily from
      midline structures. It was concluded that CRAO might be a rare complication of
      JNA embolization. Careful preoperative angiographic evaluations to detect
      communicating arteries and immediate ophthalmologic consultation in case of
      developing visual symptoms during the procedure are necessary.

PMID- 20689200
TI  - In vivo growth of retinoblastoma in a newborn infant.
AB  - Retinoblastoma is a rare malignancy of the retina seen exclusively in children.
      It is known to cause rapid growth inside the eye and hence treatment should be
      started as soon as it is diagnosed. We report a case in a five-day-old infant in
      whom treatment (chemotherapy) was delayed by a month due to high bilirubin levels
      secondary to physiological jaundice, which gave us the unique opportunity to
      measure the growth of the tumor over a month. This case emphasizes that immediate
      treatment is warranted once this rare disease is diagnosed.

PMID- 20689201
TI  - Conjunctival inclusion cysts following small incision cataract surgery.
AB  - The occurrence of acquired conjunctival inclusion cysts following various
      ophthalmic surgeries such as strabismus surgery, scleral buckling, pars plana
      vitrectomy, ptosis surgery and phacoemulsification has been reported. We report
      two cases of conjunctival inclusion cysts following manual Small Incision
      Cataract Surgery (SICS) in two male patients aged 65 and 67 years. The cysts
      originated from the scleral tunnel used for manual SICS. Both were treated by
      excision and confirmed histopathologically. No recurrence was noted at three
      months follow-up. To our knowledge, conjunctival inclusion cysts following SICS
      have not been reported previously. Careful reflection of conjunctiva during
      tunnel construction and posterior chamber intraocular lens implantation may
      prevent their occurrence.

PMID- 20689202
TI  - Hemi-central retinal artery occlusion in young adults.
AB  - Amongst the clinical presentations of retinal artery occlusion, hemi-central
      retinal artery occlusion (Hemi-CRAO) is rarely described. This case series of
      four adults aged between 22 and 36 years attempts to describe the clinical
      profile, etiology and management of Hemi-CRAO. Case 1 had an artificial mitral
      valve implant. Polycythemia and malignant hypertension were noted in Case 2. The
      third patient had Leiden mutation while the fourth patient had Eisenmenger's
      syndrome. Clinical examination and fundus fluorescein angiography revealed a
      bifurcated central retinal artery at emergence from the optic nerve head, in all
      cases. Color Doppler examination of the central retinal artery confirmed
      branching of the artery behind the lamina cribrosa. It is hypothesized that
      bifurcation of central retinal artery behind the lamina cribrosa may predispose
      these hemi-trunks to develop an acute occlusion if associated with underlying
      risk factors. The prognosis depends upon arterial recanalisation and etiology of
      the thromboembolic event.

PMID- 20689203
TI  - Regression of conjunctival tumor during dietary treatment of celiac disease.
AB  - A 3-year-old girl presented with a hemorrhagic conjunctival lesion in the right
      eye. The medical history revealed premature cessation of breast feeding,
      intolerance to the ingestion of baby foods, anorexia, and abdominal distention.
      Prior to her referral, endoscopic small intestinal biopsy had been carried out
      under general anesthesia with a possible diagnosis of Celiac Disease (CD). Her
      parents did not want their child to undergo general anesthesia for the second
      time for the excisional biopsy. We decided to follow the patient until all
      systemic investigations were concluded. In evaluation, the case was diagnosed
      with CD and the conjunctival tumor showed complete regression during gluten-free
      dietary treatment. The clinical fleshy appearance of the lesion with spider-like
      vascular extensions and subconjunctival hemorrhagic spots, possible association
      with an acquired immune system dysfunction due to CD, and spontaneous regression
      by a gluten-free diet led us to make a presumed diagnosis of conjunctival Kaposi
      sarcoma.

PMID- 20689204
TI  - Voriconazole-refractory fungal infection of phacoemulsification tunnel.
AB  - A 44-year-old man presented 28 days after cataract surgery (phacoemulsification)
      in right eye with multiple pinpoint infiltrates in posterior stroma at cataract
      surgery wound site. Visual acuity was 20/60. Corneal scraping from the floor of
      the corneal tunnel revealed fungus which was later identified to be Aspergillus
      flavus. The patient was started on oral voriconazole 200 mg twice daily and
      topical voriconazole 1% every hour. Two intracameral injections of voriconazole
      (50 micrograms/ 0.1 ml) were given 72 h apart, five days after starting initial
      therapy. Infiltrates increased in size and density in spite of 20 days of
      voriconazole therapy. Full-thickness patch graft was done to arrest progressive
      necrosis. Four months after surgery, patient had 20/60 best-corrected visual
      acuity. There was no recurrence in one-year follow-up. Present case illustrates
      the therapeutic challenge in fungal tunnel infections and possibility of
      voriconazole-resistant Aspergillus species.

PMID- 20689205
TI  - Anterior ischemic optic neuropathy precipitated by acute primary angle closure.
AB  - A 59-year-old man with a history of longstanding systemic hypotension developed
      asymmetric non-arteritic anterior ischemic optic neuropathy (NAION) apparently
      precipitated by bilateral sequential acute primary angle closure. NAION is very
      rarely reported in association with raised intraocular pressure. In contrast to
      optical coherence tomography, the failure of scanning laser polarimetry to detect
      axonal swelling was another interesting finding. Possible reasoning for these
      observations is discussed.

PMID- 20689206
TI  - Pars plana Ahmed glaucoma valve implantation with triamcinolone-assisted
      vitrectomy in refractory glaucomas.
AB  - Glaucoma drainage devices are an option in refractory glaucomas for control of
      intraocular pressure (IOP). We evaluated the outcome of pars plana Ahmed glaucoma
      valve along with triamcinolone-assisted vitrectomy in 11 eyes with uncontrolled
      IOP on maximum tolerable antiglaucoma therapy. The mean preoperative IOP of 33.64
      +/- 5.99 (range 26 to 44 mmHg) decreased to 17.09 +/- 2.26 (range 14 to 20 mmHg)
      and 17.45 +/- 1.81 mm of Hg (range 14 to 24 mmHg) at 6 and 12 months following
      surgery. The mean number of antiglaucoma medications decreased from 3.27 +/- 0.05
      to 0.64 +/- 0.67 and 0.55 +/- 0.6 at 6 and 12 months following surgery.

PMID- 20689207
TI  - Autofluorescence findings and role of anti-vascular endothelial growth factor in
      inflammatory choroidal neovascular membrane.

PMID- 20689208
TI  - Autofluorescence in posterior uveitis.

PMID- 20689209
TI  - Management of bilateral idiopathic healed sclerokeratouveitis with ciliary and
      intercalary staphyloma with complicated cataract and secondary glaucoma.

PMID- 20689210
TI  - Botulinum toxin in the management of acquired motor fusion deficiency: the
      missing links.

PMID- 20689211
TI  - Trans-scleral fixation of Cionni - modified capsule tension ring.

PMID- 20689212
TI  - Is it congenital cystic eye with dermal appendages and cerebral anomalies?

PMID- 20689213
TI  - Central serous chorioretinopathy and endogenous cortisol - is there an
      association?

PMID- 20689214
TI  - Amyloidosis of lacrimal gland: authors' reply.

PMID- 20689215
TI  - Ocular abnormalities in patients with beta thalassemia on transfusion and
      chelation therapy: our experience.

PMID- 20689216
TI  - As a member of the All India Ophthalmological Society.

PMID- 20689217
TI  - Soluble fms-like tyrosine kinase-1 and the progression of carotid intima-media
      thickness - 24-month follow-up study -.
AB  - BACKGROUND: The relationship between fms-like tyrosine kinase-1 (sFlt-1), a
      soluble receptor for vascular endothelial growth factor (VEGF), and vascular
      disease has not been established, so this study aimed to elucidate the
      association between sFlt-1 and the progression of carotid intima - media
      thickness (IMT) in hypertensive patients. METHODS AND RESULTS: The 120
      hypertensive patients under medical control were enrolled and 112 completed the
      study (age 59 +/- 9 years, 57 females). Plasma VEGF and sFlt-1 levels were
      measured at enrollment. At baseline and 24-month visit, carotid IMT was measured
      and the association between sFlt-1 and IMT progression was assessed by linear
      regression. At baseline, age (r=0.186) and low level of high-density lipoprotein
      cholesterol (HDL-C <40 mg/dl, r=0.214) were significantly related to carotid IMT.
      Over the 24 months, carotid IMT increased from 0.670 +/- 0.089 mm to 0.696 +/-
      0.095 mm. There was a positive correlation between sFlt-1 tertiles and IMT change
      (P=0.05 by ANOVA). Upon multivariate analysis, log-transformed sFlt-1 level
      (beta=0.137, P=0.003) and low HDL-C (beta=0.048, P=0.04) were identified as
      predictors of IMT progression, independent of other confounding variables.
      CONCLUSIONS: High sFlt-1 level is predictive of carotid IMT progression in
      hypertensive patients. Low HDL-C level was also associated with IMT change. These
      observations support a high sFlt-1 level being indicative of progression of
      atherosclerosis. 

PMID- 20689218
TI  - Impact of aortic plaque morphology on survival rate and incidence of a subsequent
      embolic event - long-term follow-up data -.
AB  - BACKGROUND: There are no reports about the long-term follow-up data of patients
      with aortic plaques among the Japanese population. The purpose of this study was
      to clarify the frequency of patients with severe aortic plaques and the impact of
      aortic plaque morphology on the prognosis. METHODS AND RESULTS: We
      retrospectively investigated 1,570 consecutive patients who underwent
      transesophageal echocardiography. Survival rate and subsequent embolic event rate
      were compared between patients with severe aortic plaque (>5 mm in thickness) and
      control patients. The relationship between aortic plaque morphology and prognosis
      was also estimated according to the presence of ulceration, calcification,
      hypoechoic plaques, and mobile plaques. The mean follow-up period was 8.7 years.
      Among 1,570 patients, severe aortic plaque was detected in 92 patients (5.9%).
      These 92 patients showed a significantly low survival rate and high subsequent
      embolic event rate compared to control patients (5-year survival rate: 69% vs
      94%; 5-year embolic event free rate: 52% vs 95%). Among patients with severe
      aortic plaque, only ulceration was associated with a low survival rate (hazards
      ratio: 2.4, 95% confidence interval (CI): 1.1-5.2) and only mobile plaque was
      associated with a high embolic event rate (hazards ratio: 2.2; 95%CI: 1.1-5.1).
      CONCLUSIONS: Aortic plaque >5 mm in thickness was a predictor of poor prognosis.
      In the presence of aortic plaque >5 mm, ulceration was a predictor of a low
      survival rate and mobile plaque was a predictor of a high embolic event rate.

PMID- 20689219
TI  - Autonomic function and cerebral autoregulation in patients undergoing carotid
      endarterectomy.
AB  - BACKGROUND: Carotid endarterectomy (CEA) is the first-line treatment in severe
      carotid stenosis to prevent stroke. Because of methodological limitations, the
      acute impact of CEA on baroreflex function and cerebral autoregulation is not
      well defined and was therefore investigated by applying a novel algorithm.
      METHODS AND RESULTS: Systemic arterial blood pressure, ECG and respiration during
      metronomic breathing and Valsalva maneuver were continuously recorded in 18
      patients with carotid stenosis before and after CEA, and in 10 healthy controls.
      Baroreflex sensitivity, frequency spectra of RR intervals and indices for
      cerebral autoregulation were evaluated by trigonometric regressive spectral
      analysis. Compared with the controls, patients had impaired baroreflex
      sensitivity. Baroreflex sensitivity and frequency spectra were not changed by
      CEA. Cerebral autoregulation of patients with carotid stenosis as calculated by
      phase shift was reduced compared with controls but it improved significantly
      after CEA. Improvement of cerebral autoregulation was independent of changes in
      cerebral blood flow velocity. CONCLUSIONS: Baroreflex sensitivity and cerebral
      autoregulation are impaired in patients with carotid stenosis, conferring a high
      stroke risk. CEA improves cerebral autoregulation, but does not affect baroreflex
      sensitivity. For further risk reduction, interventional approaches targeting
      baroreflex function need to be considered. 

PMID- 20689220
TI  - Gender differences in clinical and angiographic outcomes after coronary artery
      bypass surgery.
AB  - BACKGROUND: The impact of gender on outcome after coronary artery bypass grafting
      (CABG) is controversial. The aim of this study was to compare the differences of
      clinical and angiographic outcomes between female and male patients after CABG.
      METHODS AND RESULTS: The records of 954 patients who underwent isolated CABG
      between 2004 and 2009 were reviewed. There were 188 female and 766 male patients.
      Female patients were smaller (P<0.0001) and had a more unstable status (P=0.0024)
      preoperatively compared with the male patients. Left internal thoracic artery
      (ITA) use was identical in both genders. However, the right ITA (P=0.006) and
      radial artery (P<0.0001) use were less frequent in females compared with that in
      males. Consequently, the use of saphenous vein grafts (SVGs) was more frequent in
      females than in males (P<0.0001). Mortality was similar between the genders (1.0%
      vs 1.1%). Although the rate of major complications was not significantly
      different between the genders (12.2% vs 9.5%), the cerebrovascular event rate was
      higher in females compared with that in males (4.3% vs 1.6%; P=0.0432). Patency
      rates of arterial grafts were not significantly different between the genders;
      however, those of SVGs were lower in females than those in males (88.6% vs 96.1%;
      P=0.0003). CONCLUSIONS: The clinical outcomes of females after CABG were
      comparable with those of males.

PMID- 20689221
TI  - Short- and mid-term intravascular ultrasound analysis of the new zotarolimus
      eluting stent with durable polymer - results from the RESOLUTE trial -.
AB  - BACKGROUND: The Resolute stent is a newly developed system with a bio
      histocompatible polymer that allows programmed drug delivery up to 180 days. The
      aim of this intravascular ultrasound (IVUS) analysis was to evaluate the short-
      (4 months) and mid-term (9 months) efficacy using the Resolute stent. METHODS AND
      RESULTS: Data were derived from the RESOLUTE trial, a prospective, multicenter,
      non-randomized, single-arm study to treat de novo native coronary artery lesions.
      This trial included 2 cohorts with different follow-up periods, and all
      enrollment patients in this trial received IVUS study. Follow-up IVUS was
      available in 24 patients (4-month group) and 88 patients (9-month group).
      Neointimal obstruction (%) was defined as neointimal volume divided by stent
      volume. Cross-sectional narrowing (CSN, %) was defined as neointimal area divided
      by stent area. No significant differences in vessel, lumen and stent volume at
      post-procedure were observed within stented segments between the 4- and 9-month
      follow-up groups. Although neointimal volume and % neointimal obstruction showed
      no significant difference between the 2 groups (% neointimal obstruction: 2.2 +/-
      2.5 vs 3.7 +/- 4.0%, P=0.09), maximum CSN was significantly larger in the 9-month
      group. There were 7 cases of late incomplete stent apposition. CONCLUSIONS: These
      IVUS results showed minimum growth of neointimal proliferation by the Resolute
      stent throughout the stented segment up to 9 months follow up. 

PMID- 20689222
TI  - Urgent announcement from the editor-in-chief regarding duplicate publication.

PMID- 20689223
TI  - Possible health-protecting effects of feeling useful to others on symptoms of
      depression and sleep disturbance in the workplace.
AB  - OBJECTIVES: The aim of this study was to examine the health-protecting effects of
      feeling useful to others on symptoms of depression and sleep disturbance in the
      workplace, as well as its buffering effects on associations between stressful
      work environments and symptoms of depression and sleep disturbance. METHODS: The
      subjects of this cross-sectional survey were 773 Japanese workers (response rate:
      64.8%) of five organizations. Feelings of being useful to others were assessed
      with one simple question used in a previous study. Psychosocial work environment,
      sleep disturbance, and depressive symptoms were assessed using the Japanese
      versions of the Effort-Reward Imbalance Questionnaire, the Pittsburgh Sleep
      Quality Index, and the 28-item General Health Questionnaire, respectively. We
      tested for linear and interactive effects with hierarchical regression analyses.
      RESULTS: Feeling useful to others was significantly (p<0.05) and negatively
      associated with scores of depression and sleep disturbance both in the univariate
      analyses and after adjusting for age in both genders. Significant (p<0.05)
      interactions showed that, in both genders, as the effort-reward balance worsened,
      symptoms of depression increased, but feeling useful to others buffered the
      associations. CONCLUSIONS: The results support the notion that feeling useful to
      others in both genders in the workplace has possible health-protecting effects.

PMID- 20689224
TI  - Molecular analysis of Cryptosporidium parvum HNJ-1 isolated in Japan.
AB  - Cryptosporidium parvum HNJ-1 is widely used as a reference strain in Japan. In
      the present study, the parasite was subjected for further molecular analysis
      including transcribed ribosomal region (ITS rRNA), dihydrofolate reductase (DHFR)
      and surface glycoprotein (GP60) genes. Partial sequence analysis of these genes
      indicated extensive polymorphism in ITS region compared with relevant sequences
      of other Cryptosporidium parvum isolates. In addition, this strain was identified
      as C. parvum IIaA15G2R1 subtype, based on the sequence results of GP60 gene
      locus.

PMID- 20689225
TI  - Virulence genes and antimicrobial susceptibilities of hemolytic and nonhemolytic
      Escherichia coli isolated from post-weaning piglets in central Thailand.
AB  - The purpose of this study was to compare the existence of virulence genes in
      hemolytic Escherichia coli (HEC) and nonhemolytic E. coli (NHEC) isolated from
      weaner pigs in Thailand, and to determine their susceptibility to 10
      antimicrobial agents. A total of 304 E. coli isolates were obtained from 90
      piglets with diarrhea and 110 healthy piglets. Of these, 74 HEC isolates were
      obtained from 70 pigs with diarrhea, and 4 were obtained from 4 healthy pigs,
      while 190 and 40 NHEC were recovered from 110 healthy and 20 pigs with diarrhea,
      respectively. A ten digoxigenin (DIG)-labeled probe system was utilized for
      detecting genes encoding virulence-associated toxins and proteins in these
      isolates, and the minimal inhibitory concentration values against 10
      antimicrobials were determined by means of the agar dilution technique. In total,
      70.3% of the HEC isolates contained an exotoxin gene, lth, estp or stx2e, whereas
      2.6% of the NHEC isolates hybridized with a gene probe for estp or stx2e. Over
      90% of the isolates were resistant to most agents other than colistin and
      halquinol. The MIC(90) values of the HEC isolates for halquinol and colistin were
      4 and 8 times greater than those of the NHEC isolates, respectively. The results
      represent the first characterization of resistant pathogenic E. coli distributed
      in the Thai pig industry. Amongst the HEC isolates, there appeared to be an
      association between the presence of some exotoxin genes, including lth, estp and
      stx2e, and reduced antimicrobial susceptibility.

PMID- 20689226
TI  - Phase transition in spin systems with various types of fluctuations.
AB  - Various types ordering processes in systems with large fluctuation are
      overviewed. Generally, the so-called order-disorder phase transition takes place
      in competition between the interaction causing the system be ordered and the
      entropy causing a random disturbance. Nature of the phase transition strongly
      depends on the type of fluctuation which is determined by the structure of the
      order parameter of the system. As to the critical property of phase transitions,
      the concept "universality of the critical phenomena" is well established.
      However, we still find variety of features of ordering processes. In this
      article, we study effects of various mechanisms which bring large fluctuation in
      the system, e.g., continuous symmetry of the spin in low dimensions,
      contradictions among interactions (frustration), randomness of the lattice,
      quantum fluctuations, and a long range interaction in off-lattice systems.

PMID- 20689227
TI  - ATP synthase: from single molecule to human bioenergetics.
AB  - ATP synthase (F(o)F(1)) consists of an ATP-driven motor (F(1)) and a H(+)-driven
      motor (F(o)), which rotate in opposite directions. F(o)F(1) reconstituted into a
      lipid membrane is capable of ATP synthesis driven by H(+) flux. As the basic
      structures of F(1) (alpha(3)beta(3)gammadeltaepsilon) and F(o) (ab(2)c(10)) are
      ubiquitous, stable thermophilic F(o)F(1) (TF(o)F(1)) has been used to elucidate
      molecular mechanisms, while human F(1)F(o) (HF(1)F(o)) has been used to study
      biomedical significance. Among F(1)s, only thermophilic F(1) (TF(1)) can be
      analyzed simultaneously by reconstitution, crystallography, mutagenesis and
      nanotechnology for torque-driven ATP synthesis using elastic coupling mechanisms.
      In contrast to the single operon of TF(o)F(1), HF(o)F(1) is encoded by both
      nuclear DNA with introns and mitochondrial DNA. The regulatory mechanism, tissue
      specificity and physiopathology of HF(o)F(1) were elucidated by proteomics, RNA
      interference, cytoplasts and transgenic mice. The ATP synthesized daily by
      HF(o)F(1) is in the order of tens of kilograms, and is primarily controlled by
      the brain in response to fluctuations in activity.

PMID- 20689228
TI  - Transthyretin-related familial amyloidotic polyneuropathy-Progress in Kumamoto,
      Japan (1967-2010)-.
AB  - The authors reviewed contribution of Kumamoto University group to the progress of
      the studies on transthyretin (TTR)-related familial amyloidotic polyneuropathy
      (TTR-related FAP) for 42 years (from 1967 to 2009). Andrade (1952) first
      described a large group of patients with FAP in Portugal and Araki et al. (1967)
      in second discovered similar FAP patients in Arao, Kumamoto, Japan. Owing to
      progress in biochemical and molecular genetic analyses, FAP is now believed to
      occur worldwide. As of today, reports of about 100 different points of single or
      two mutations, or a deletion in the transthyretin (TTR) gene, have been
      published. The authors' group has made pioneer works for study of FAP in the
      world. The focus on therapy in amylodosis will increase sharply as an impetus in
      near future, and successful treatments are expected.

PMID- 20689229
TI  - Reminiscence of 40-year research on nitrogen metabolism.
AB  - This article summarizes my research over 40 years. The main theme of my work is
      nitrogen metabolism of amino acids, though later I focused on protein turnover in
      the cell. In the first years of my research work, I was busy dissecting the
      pathways involved in the metabolism of certain amino acids and their related
      enzymes. Then I became interested in the physiology and regulation of matabolism
      of these amino acids. For that, I used primary cultured hepatocytes, which
      contain many liver-specific enzymes. However, this play field was very rough
      around 1970 and hence I had to smooth them (differentiated) first. We discovered
      a specific growth factor (hepatocyte growth factor, HGF) in rat platelets.
      Exceptionally, I also worked on branched chain amino acids (valine, leucine and
      isoleucine). These amino acids are not efficiently metabolized in the liver, so I
      had to consider the physiology of extrahepatic tissues as well. Finally, I came
      across a huge protease complex, the proteasome. Whether these players, small
      amino acid metabolizing enzymes and the huge protease complex, danced well in
      harmony on my playground or not, I still do not know.

PMID- 20689230
TI  - Interleukin 6 in autoimmune and inflammatory diseases: a personal memoir.
AB  - In this review, the author discusses the research that led to the identification
      and characterization of interleukin 6 (IL-6), including his own experience
      isolating IL-6, and the roles this cytokine has on autoimmune and inflammatory
      diseases. The cDNAs encoding B-cell stimulatory factor 2 (BSF-2), interferon
      (IFN)-beta2 and a 26-kDa protein were independently cloned in 1986, which in turn
      led to the identification of each. To resolve the confusing nomenclature, these
      identical molecules were named IL-6. Characterization of IL-6 revealed a
      multifunctional cytokine that is involved in not only immune responses but also
      hematopoiesis, inflammation, and bone metabolism. Moreover, IL-6 makes
      significant contributions to such autoimmune and inflammatory diseases as
      rheumatoid arthritis (RA).IL-6 activates both the STAT3 and SHP2/Gab/MAPK
      signaling pathways via the gp130 signal transducer. F759 mice, which contain a
      single amino-acid substitution in gp130 (Y759F) and show enhanced STAT3
      activation, spontaneously develop a RA-like arthritis as they age. F759 arthritis
      is dependent on CD4(+) T cells, IL-6, and IL-17A, and is enhanced by the pX gene
      product from human T cell leukemia virus 1 (HTLV-1). Arthritis development in
      these mice requires that the F759 mutation is present in nonhematopoietic cells,
      but not in immune cells, highlighting the important role of the interaction
      between nonimmune tissues and the immune system in this disease. Furthermore,
      this interaction is mediated by the IL-6 amplifier through STAT3 and NF-kappaB.
      Ultimately, this model may represent a general etiologic process underlying other
      autoimmune and inflammatory diseases. More importantly, the understanding of IL-6
      has paved the way for new therapeutic approaches for RA and other autoimmune and
      inflammatory diseases.

PMID- 20689232
TI  - Progress in muscular dystrophy research with special emphasis on gene therapy.
AB  - Duchenne muscular dystrophy (DMD) is an X-linked, progressive muscle-wasting
      disease caused by mutations in the DMD gene. Since the disease was described by
      physicians in the 19th century, information about the subject has been
      accumulated. One author (Sugita) was one of the coworkers who first reported that
      the serum creatine kinase (CK) level is elevated in progressive muscular
      dystrophy patients. Even 50 years after that first report, an elevated serum CK
      level is still the most useful marker in the diagnosis of DMD, a sensitive index
      of the state of skeletal muscle, and useful to evaluate therapeutic effects. In
      the latter half of this article, we describe recent progress in the therapy of
      DMD, with an emphasis on gene therapies, particularly exon skipping.

PMID- 20689231
TI  - Structures and application of oligosaccharides in human milk.
AB  - Comparative study of the oligosaccharide profiles of individual human milk
      revealed the presence of three different patterns. Four oligosaccharides
      containing the Fucalpha1-2Gal group were missing in the milk of non-secretor, and
      three oligosaccharides containing the Fucalpha1-4GlcNAc group were missing in the
      milk of Lewis negative individuals. Disappearance of some major oligosaccharides
      in these samples led to the finding of five novel minor oligosaccharides, which
      were hidden under the missing oligosaccharides. Following these studies,
      structures of many novel milk oligosaccharides were elucidated. At least 13 core
      oligosaccharides were found in these oligosaccharides. By adding alpha-fucosyl
      residues and sialic acid residues to these core oligosaccharides, more than one
      hundred oligosaccharides were formed. All these oligosaccharides contain lactose
      at their reducing termini. This evidence, together with the deletion phenomena
      found in the milk oligosaccharides of non-secretor and Lewis negative
      individuals, suggested that the oligosaccharides are formed from lactose by the
      concerted action of glycosyltransferases, which are responsible for elongation
      and branching of the Galbeta1-4GlcNAc group in the sugar chains of
      glycoconjugates on the surface of epithelial cells. Therefore, oligosaccharides
      in human milk could include many structures, starting from the Galbeta1-4GlcNAc
      group in the sugar chains of various glycoconjugates. Many lines of evidence
      recently indicated that virulent enteric bacteria and viruses start their
      infection by binding to particular sugar chains of glycoconjugates on the target
      cell surfaces. Therefore, milk oligosaccharides could be useful for developing
      drugs, which inhibit the infection of bacteria and viruses.

PMID- 20689233
TI  - Molecular characterization of O-methyltransferases involved in isoquinoline
      alkaloid biosynthesis in Coptis japonica.
AB  - O-Methyltransferases, which catalyze the production of small molecules in plants,
      play a crucial role in determining biosynthetic pathways in secondary metabolism
      because of their strict substrate specificity. Using three O-methyltransferase
      (OMT) cDNAs that are involved in berberine biosynthesis, we investigated the
      structure that was essential for this substrate specificity and the possibility
      of creating a chimeric enzyme with novel substrate specificity. Since each OMT
      has a relatively well-conserved C-terminal putative S-adenosyl-L-methionine
      binding domain, we first exchanged the N-terminal halves of different OMTs. Among
      the 6 combinations that we tested for creating chimeric OMTs, 5 constructs
      produced detectable amounts of recombinant proteins, and only one of these with
      an N-terminal half of 6-OMT and a C-terminal half of 4'-OMT (64'-OMT) showed
      methylation activity with isoquinoline alkaloids as a substrate. Further
      enzymological analysis of 64'-OMT reaction product indicated that 64'-OMT
      retained the regio-specificity of 6-OMT. Further examination of the N-terminal
      region of 64'-OMT showed that about 90 amino acid residues in the N-terminal half
      were critical for reaction specificity. The creation of OMTs with novel
      reactivity is discussed.

PMID- 20689234
TI  - [Analysis of case studies to evaluate supports for depressive white-collar
      workers who are returning to work after sick leave].
AB  - PURPOSE: In Japan, mental health problems due to work stress among white-collar
      workers have become an important topic which needs to be addressed. As for the
      support for workers who are returning to work after sick leave, reliable findings
      have not yet been reported. The purpose of the present study was to obtain
      findings concerning support for workers who are returning to work after sick
      leave. METHOD: We analyzed cases studies of white-collar workers between Jan.
      1983 and May 2009. RESULTS: We identified 9 types of support; sick leave, change
      of work place, change of boss, change of work, decreasing work load, introduction
      of a decreased work load period, limiting work, consultation with corporate
      health care staff, and intervention by a party other than the company.
      DISCUSSION: Generally speaking, it has been revealed that each support has both
      positive and negative influences upon employees returning to work. In addition,
      consulting with corporate health care staff (p<0.01) showed significantly higher
      rates of no relapse into depression than in the absence of such consulting.
      However, this finding might be accompanied with a problem of potential bias with
      respect to published articles, and the relationship between health care
      professionals (i.e., physicians, occupational nurses, counselors, etc.) and a
      depressive worker. In addition, the content and date of a company's support for a
      worker returning to work might vary significantly. Thus, we need to be very
      careful in interpreting these findings.

PMID- 20689235
TI  - Mesio-distal tooth angulation in elderly with many remaining teeth observed by 3
      D imaging.
AB  - Few studies have investigated the morphologic characteristics of teeth, dental
      arches and occlusion in elderly persons with many remaining teeth. The purpose of
      this study was to establish a method of measurement using 3-D imaging to
      investigate tooth angulation in the elderly from the orthodontic point of view.
      The dental casts of 20 elderly persons with many remaining teeth were digitized
      with a 3-D laser scanner (VMS-100F, UNISN INC., Osaka, Japan) to construct 3-D
      images. The mesio-distal angulation of each tooth was then measured with
      analytical software (SURFLACER, UNISN INC. and IMAGEWARE 12, UGS PLM Solutions,
      MO, USA). The occlusal plane formed by the incisal edge of the central incisor
      and distal buccal cusp tip of the first molar on either side was used as a
      reference plane for measurements. Mesio-distal tooth angulation (indicated in
      degrees) of maxillary teeth in this subjects averaged 1.26 for central incisors,
      5.46 for lateral incisors, 7.84 for canines, 6.59 for first premolars, 5.78 for
      second premolars, 1.64 for first molars and -4.17 for second molars. Average
      values for mandibular teeth were 0.91 for central incisors, 2.35 for lateral
      incisors, 7.04 for canines, 8.76 for first premolars, 10.44 for second premolars,
      7.33 for first molars and 12.67 for second molars. There was no statistical
      difference between the data in man and women except maxillary second molar
      (p<0.05). Mesial angulation in the mandibular arch showed a progressive increase
      from the anterior to the posterior. However, this tendency was not observed in
      the maxillary arch.

PMID- 20689236
TI  - Color differences between artificial and natural teeth in removable partial
      denture wearers.
AB  - The purpose of this study was to investigate differences between natural tooth
      color and that selected for artificial teeth in partial dentures at our
      department with a view to establishing criteria for obtaining greater
      harmonization between colors. The participants in this study comprised partial
      denture wearers visiting the Department of Prosthodontics, Tokyo Dental College
      Chiba Hospital, in whom both artificial teeth and natural teeth were present in
      the maxillary anterior tooth area. Natural tooth color was measured according to
      VITA classical shade guide number using a dental color measurement apparatus.
      Artificial tooth color in partial dentures produced at our department was
      investigated by referring to medical records. Color of 28 participants' natural
      teeth and 345 participants' artificial teeth was investigated. Differences in
      color distribution between the natural and artificial tooth were analyzed using
      the Fisher exact test. The most frequent color of natural tooth was C-type,
      accounting for 39%, followed by D- at 32%, A-at 22% and B-type at 7%. In terms of
      artificial tooth color, A-type was the most common (97%). The color distribution
      of natural teeth differed significantly from that of artificial teeth in partial
      dentures. These results suggest that artificial tooth color did not harmonize
      with the color of the natural teeth in partial denture wearers.

PMID- 20689237
TI  - Tooth inclination in elderly with many remaining teeth observed by 3-D imaging.
AB  - Tooth inclination has been discussed many times in terms of esthetics and
      functionality, but reports related to aging are extremely rare. The purpose of
      this study was to evaluate tooth inclination in the elderly from the orthodontic
      point of view. The dental casts of twenty elderly persons with many remaining
      teeth were digitized with a 3-D laser scanner (VMS-100F,UNISN INC., Osaka, Japan)
      for reconstruction into 3-D images. Inclination of each tooth was then measured
      with an analytical software (SURFLACER, UNISN INC. and IMAGEWARE 12, UGS PLM
      Solutions, MO, USA). The occlusal plane formed by the incisal edge of the central
      incisor and distal buccal cusp tip of the first molar on either side was used as
      a reference plane to measure tooth inclination, and the complementary angle as
      tooth inclination was measured. The average tooth inclinations (degrees) of the
      maxillary teeth were 8.08 for central incisors, 8.10 for lateral incisors, 4.85
      for canines, -6.68 for first premolars, -5.58 for second premolars, -5.15 for
      first molars, and -5.41 for second molars. The corresponding values for the
      mandibular teeth were 6.78 for central incisors, 4.87 for lateral incisors, -5.73
      for canines, -13.74 for first premolars, -19.21 for second premolars, -23.76 for
      first molars, and -28.63 for second molars. There was no statistical difference
      between men and women, except for in the maxillary lateral incisors (p<0.05).
      Tooth inclination showed a progressive decrease from anterior to posterior. The
      decrease in the mandibular teeth was more regular than that of the maxillary
      teeth.

PMID- 20689238
TI  - Dental erosion in workers exposed to sulfuric acid in lead storage battery
      manufacturing facility.
AB  - Dental erosion, and specifically its symptoms, has long been studied in Japan as
      an occupational dental disease. However, in recent years, few studies have
      investigated the development of this disease or labor hygiene management aimed at
      its prevention. As a result, interest in dental erosion is comparatively low,
      even among dental professionals. Our investigation at a lead storage battery
      factory in 1991 found that the work environmental sulfuric acid density was above
      the tolerable range (1.0mg/m(3)) and that longterm workers had dental erosion.
      Therefore, workers handling sulfuric acid were given an oral examination and
      rates of dental erosion by tooth type, rates of erosion by number of working
      years and rates of erosion by sulfuric acid density in the work environment
      investigated. Where dental erosion was diagnosed, degree of erosion was
      identified according to a diagnostic criterion. No development of dental erosion
      was detected in the maxillary teeth, and erosion was concentrated in the anterior
      mandibular teeth. Its prevalence was as high as 20%. Rates of dental erosion rose
      precipitously after 10 working years. The percentages of workers with dental
      erosion were 42.9% for 10-14 years, 57.1% for 15-19 years and 66.7% for over 20
      years with 22.5% for total number of workers. The percentages of workers with
      dental erosion rose in proportion to work environmental sulfuric acid density:
      17.9% at 0.5-1.0, 25.0% at 1.0-4.0 and 50.0% at 4.0-8.0mg/m(3). This suggests
      that it is necessary to evaluate not only years of exposure to sulfuric acid but
      also sulfuric acid density in the air in factory workers.

PMID- 20689239
TI  - Treatment of periodontal defects with enamel matrix derivative: clinical
      evaluation at early healing stages.
AB  - The aim of this retrospective clinical study was to evaluate the treatment of
      intrabony periodontal defects with enamel matrix derivative (EMD) during the
      early stages of healing. Sixteen patients aged 38-77 years with a clinical
      diagnosis of chronic periodontitis were subjected to data analysis. A total of 25
      teeth with various osseous defects received regenerative therapy with EMD, and
      were followed for a minimum of 6 months. Post-operative healing was uneventful in
      the majority of cases. Treatment of the intrabony defects with EMD led to a
      statistically significant improvement in the mean value of probing depth at 3
      months compared with that at baseline (p<0.001). Mean values of attachment gain
      at 3 and 6 months were of clinical significance: 3.6+/-1.8mm and 3.2+/-1.5mm,
      respectively. Reduction in probing depth was achieved with minimal recession of
      gingival margin and was sustained over a time course of 6 months. A progressive
      increase in radiopacity, suggestive of initial signs of bone-fill, was observed
      by 6 months. In summary, the results suggest that treatment of intrabony defect
      with EMD induces favorable periodontal healing with a high level of
      predictability.

PMID- 20689240
TI  - Survey of accidental ingestion and aspiration at Tokyo Dental College Chiba
      Hospital.
AB  - The occurrence of accidental ingestion/aspiration and preventive measures were
      investigated at Tokyo Dental College Chiba Hospital. In addition, the
      characteristics of accidents at our hospital were analyzed by surveying the
      awareness of accidental ingestion/aspiration to utilize the data for prevention.
      Accidental ingestion accounted for about 30% of accidents that occurred at our
      hospital in fiscal 2008, but all ingested items were naturally excreted, and no
      accidental aspiration occurred. Accidental ingestion most frequently occurred
      when dental restorations were removed. Inlays and crowns were most frequently
      ingested, and dentists with 5 to less than 10 years of clinical experience tended
      to be involved in these accidents. According to the results of the questionnaire,
      removal of restorations was perceived as the treatment least likely to cause
      accidental ingestion/aspiration. Moreover, dentists who always took preventive
      measures against accidental ingestion/aspiration accounted for only 40% or less
      on average. To avoid accidental ingestion/aspiration, repeated courses and
      individual instruction for repeaters and the establishment of a surveillance
      system along with manuals to manage the violation should be emphasized.

PMID- 20689241
TI  - Matching system within clinical training facilities group of clinical dental
      training in Tokyo Dental College Chiba Hospital.
AB  - Since clinical dental training became mandatory in April 2006, Tokyo Dental
      College Chiba Hospital has been offering the following two types of training
      system: 1. a single system, and 2. a clinical training facilities group system.
      The clinical training facilities group system consists of program B, in which
      residents are trained in a cooperation-type clinical training facility for 3-4
      months, and program C, in which residents are trained in two cooperation-type
      clinical training facilities for 7-8 months. A matching system within the
      clinical training facilities group is applied to select and decide on the
      cooperation-type clinical training facility for residents. In this system, the
      ranking of resident candidates that a cooperation-type clinical training facility
      would like to accept, and the ranking of training facilities that candidates
      choose are matched. The present study investigated the matching system within the
      clinical training facilities group in 2006, 2007, and 2008. The rate of matching
      to their third choice was more than 90% in program B and about 80% in program C
      in each year, suggesting a high matching rate. The percentage of cooperation-type
      clinical training facilities accepting dental residents dropped due to a decrease
      in the number of such residents. The distribution of accepted cooperation-type
      clinical training facilities is concentrated in Chiba Prefecture where our
      hospital, the management-type clinical training facility, is located, and the
      neighboring prefectures.

PMID- 20689242
TI  - Effect of huprine X on beta-amyloid, synaptophysin and alpha7 neuronal nicotinic
      acetylcholine receptors in the brain of 3xTg-AD and APPswe transgenic mice.
AB  - BACKGROUND: Several studies implicate acetylcholinesterase (AChE) in the
      pathogenesis of Alzheimer's disease (AD), raising the question of whether
      inhibitors of AChE also might act in a disease-modifying manner. Huprine X (HX),
      a reversible AChE inhibitor hybrid of tacrine and huperzine A, has shown to
      affect the amyloidogenic process in vitro. In this study, the aim was to
      investigate whether HX could affect the AD-related neuropathology in vivo in two
      mouse models. METHODS: Tg2576 (K670M/N671L) (APPswe) and 3xTg-AD (K670M/N671L,
      PS1M146V, tauP301L) mice were treated with HX (0.12 MUmol/kg, i.p., 21 days) or
      saline at 6-7 months. Human beta-amyloid (Abeta) was measured by ELISA,
      synaptophysin by Western blot and alpha7 neuronal nicotinic acetylcholine
      receptors (nAChRs) were analyzed by [(125)I]alpha-bungarotoxin autoradiography.
      RESULTS: Treatment with HX reduced insoluble Abeta1-40 (about 40%) in the
      hippocampus of 3xTg-AD mice, while showing no effect in APPswe mice.
      Additionally, HX markedly increased cortical synaptophysin levels (about 140%)
      and decreased (about 30%) the levels of alpha7 nAChRs in the caudate nucleus of
      3xTg-AD mice, while increasing (about 10%) hippocampal alpha7 nAChRs in APPswe
      mice. CONCLUSION: The two mouse models react differently to HX treatment,
      possibly due to their differences in brain neuropathology. The modulation of
      Abeta and synaptophysin by HX in 3xTg-AD mice might be due to its suggested
      interaction with the peripheral anionic site on AChE, and/or via cholinergic
      mechanisms involving activation of cholinergic receptors. Our results provide
      further evidence that drugs targeting AChE affect some of the fundamental
      processes that contribute to neurodegeneration, but whether HX might act in a
      disease-modifying manner in AD patients remains to be proven.

PMID- 20689243
TI  - Trisomy of the short stature homeobox-containing gene (SHOX) due to
      duplication/deletion of the X chomosome: clinical implications on the stature.
AB  - BACKGROUND: The karyotypes of 2 patients with abnormal stature and different
      phenotypes revealed one similar structural abnormality in the X chromosome by
      conventional cytogenetic studies and fluorescence in situ hybridization analysis
      (FISH). FISH strongly suggested the presence of two copies of the SHOX gene in
      the der(X) chromosome. PATIENTS AND RESULTS: Patient 1 is a teenager girl with
      tall stature, behavioral disturbances and normal pubertal development. The
      abnormal X chromosome was present in all cells studied. Parent's karyotypes were
      normal. Patient 2 is a girl with gonadal dysgenesis, mild Turner syndrome
      phenotype and short stature. The karyotype was a mosaic 45,X/46,X,r(X) and der(X)
      chromosome presented in most metaphases of the cell lines. Parent's karyotypes
      were normal. Nearly all duplication of Xp and partial deletion of the long arm
      (Xq) from Xq27 or Xq21 to Xqter, in cases 1 and 2, respectively, were observed.
      In both patients, duplication of Xp translocated to deleted Xq occurred leading
      to a triplication of the pseudoautosomal region 1 (PAR1) where the SHOX gene is
      located (Xp22.3). CONCLUSIONS: We propose that in some cases of trisomy for the
      SHOX gene, the effect of overdosage per se may affect the stature, even in
      patients with preserved ovarian function (case 1), and that estrogen deprivation
      may not always be a contributor for tall stature (case 2).

PMID- 20689244
TI  - 'Access arrangements' for biobanks: a fine line between facilitating and
      hindering collaboration.
AB  - This decade is witnessing the proliferation of large-scale population-based
      biobanks. Many biobanks have reached the stage of offering access to their
      collection of data and samples to the scientific community. This, however,
      requires that access arrangements be established to govern the relationship
      between biobanks and users. Access arrangements capture the convergence of all
      normative elements in the life cycle of a biobank: policies, laws, common
      practices, commitments made by the biobank to participants, the expectations of
      funders, and the needs of the scientific community. Furthermore, access
      arrangements shape new legal agreements between 'biobankers' and researchers to
      ensure appropriate, regulated and efficient use of biobank materials. This paper
      begins by examining the particularities of access arrangements, identifying the
      key elements of these new regulatory instruments. Second, the paper looks at
      various strategies used by biobanks to regulate access and surveys the underlying
      motivations of these strategies and the impact they can have on potential
      international collaboration. Third, an example of the challenges encountered in
      creating access policy is illustrated using the case of CARTaGENE, a biobank
      based in Montreal, Canada. Last, the paper presents how Public Population Project
      in Genomics (P(3)G) facilitates the work of biobankers and improves collaboration
      throughout the international human genomics research community.

PMID- 20689245
TI  - The incidence and prevalence of Alzheimer's disease.
AB  - The prevalence of Alzheimer's disease (AD) has grown progressively over the past
      100 years. The present study monitored the evolution of AD incidence in relation
      to several factors known as favoring it, in a county in Romania, between 1980 and
      2006. The annual incidence of AD in our clinic over a period of 27 years was
      determined along with 17 hereditary, medical, sociodemographic and environmental
      parameters. The results show a relatively steady curve until 1994, followed by a
      doubling of the incidence with a tendency to continuous growth. During this
      period, none of the known pathogenic factors--medical, psychological or
      sociodemographic--suffered any mathematically significant transformation. The
      only significant change for this population was the access to industrialized and
      preserved food and fizzy drinks which came from the western world, immediately
      after the borders had opened (1989). Therefore, the cause of the increased AD
      incidence must be looked for in food hygiene, and we must accept the notion of an
      ecologically caused disease.

PMID- 20689246
TI  - Prenatal flutamide enhances survival in a myogenic mouse model of spinal bulbar
      muscular atrophy.
AB  - BACKGROUND: Spinal bulbar muscular atrophy (SBMA) is caused by a CAG repeat
      expansion mutation in the androgen receptor (AR) gene, and mutant AR is presumed
      to act in motoneurons to cause SBMA. However, we found that mice overexpressing
      wild-type (wt) AR solely in skeletal muscle fibers display the same androgen
      dependent disease phenotype as when mutant AR is broadly expressed, challenging
      the assumptions that only an expanded AR can induce disease and that SBMA is
      strictly neurogenic. We have previously reported that AR toxicity was ligand
      dependent in our model, and that very few transgenic (tg) males survived beyond
      birth. METHODS: We tested whether the AR antagonist flutamide could block
      perinatal toxicity. tg males were treated prenatally with flutamide and assessed
      for survival and motor behavior in adulthood. RESULTS: Prenatal treatment with
      flutamide rescued tg male pups from perinatal death, and, as adults, such
      perinatally rescued tg males showed an SBMA phenotype that was comparable to that
      of previously described untreated tg males. Moreover, tg males carrying a mutant
      endogenous allele for AR--the testicular feminization mutation (tfm)--and thus
      having functional AR only in muscle fibers nevertheless displayed the same
      androgen-dependent disease phenotype as adults. CONCLUSIONS: These mice represent
      an excellent model to study the myogenic contribution to SBMA as they display
      many of the core features of disease as other mouse models. These data
      demonstrate that AR acting exclusively in muscle fibers is sufficient to induce
      SBMA symptoms and that flutamide is protective perinatally.

PMID- 20689247
TI  - TASTPM mice expressing amyloid precursor protein and presenilin-1 mutant
      transgenes are sensitive to gamma-secretase modulation and amyloid-beta42
      lowering by GSM-10h.
AB  - BACKGROUND: Cleavage of the amyloid precursor protein (APP) by beta-site APP
      cleaving enzyme and gamma-secretase results in the generation of amyloid-beta
      (Abeta) peptides that aggregate and deposit as senile plaques in brains of
      Alzheimer disease patients. Due to the fundamental role gamma-secretase plays in
      the proteolysis of a number of proteins including Notch, pharmacological
      inhibition of gamma-secretase has been associated with mechanism-based
      toxicities. Therefore, efforts have focussed on the modulation of gamma-secretase
      activity to selectively decrease levels of Abeta42 peptide while avoiding
      deleterious activity on Notch processing. OBJECTIVE: Here, we describe the in
      vitro and in vivo characterisation of a novel gamma-secretase modulator, GSM-10h,
      and investigate the potential for shorter Abeta peptides to induce neurotoxicity
      in rat primary cortical neurons. METHODS: The effect of GSM-10h on Abeta levels
      was investigated in SH-SY5Y cells expressing mutant APP and in TASTPM mice
      expressing APP and presenilin-1 mutant transgenes. The effect of GSM-10h on Notch
      processing was also determined. RESULTS: In cells, GSM-10h decreased levels of
      Abeta42 while concomitantly increasing levels of Abeta38 in the absence of
      effects on Abeta40 levels. In TASTPM mice, GSM-10h effectively lowered brain
      Abeta42 and increased brain Abeta38, with no effect on Notch signalling. Unlike
      Abeta42, which causes neuronal cell death, neither Abeta37 nor Abeta38 were
      neurotoxic. CONCLUSIONS: These findings confirm GSM-10h exhibits the profile of a
      gamma-secretase modulator. In addition, TASTPM mice are shown to be responsive to
      treatment with a gamma-secretase modulator, thereby highlighting the utility of
      this bitransgenic mouse model in drug discovery efforts focussed on the
      development of gamma-secretase modulators.

PMID- 20689248
TI  - Parental attitudes toward ethical and social issues surrounding the expansion of
      newborn screening using new technologies.
AB  - AIMS: This study assessed parent knowledge of newborn screening (NBS) and parent
      attitudes toward NBS for untreatable conditions, NBS for late-onset disorders and
      informed consent in NBS. METHODS: Seventeen qualitative focus groups were held in
      Alaska, California, Hawaii, and Washington with mothers of children 10 years old
      or younger. RESULTS: Most participants did not recall receiving information about
      NBS, and all wanted this information prenatally. In addition, most felt that the
      current system of 'informed dissent' was adequate, provided they were told about
      NBS prior to delivery. All women supported NBS for conditions that occur in
      infancy without a proven treatment. However, they disagreed about NBS for
      disorders that manifest in late childhood or adulthood. CONCLUSIONS: The results
      show a general consensus among the focus group participants about issues that
      cause dissent among public health and health care professionals. Parent attitudes
      differ from those of many professional communities with regard to timing of NBS
      education, informed consent, NBS for disorders that lack an effective treatment,
      and predictive testing of children for late-onset disorders. The results
      highlight the need to further research parent opinions about expanded NBS using
      new technologies and to include parents in the development of NBS policies.

PMID- 20689249
TI  - Matrix Gla protein expression in NRK-52E cells exposed to oxalate and calcium
      oxalate monohydrate crystals.
AB  - PURPOSE: Matrix Gla protein (MGP), a potent calcification inhibitor in
      extracellular matrix, is a molecular determinant regulating vascular
      calcification. Here, we characterized MGP expression in cultured renal tubular
      epithelial cells exposed to oxalate and calcium oxalate monohydrate (COM)
      crystals. METHODS: NRK-52E cells were cultured and exposed to medium containing
      oxalate or COM for 1, 3, 6, 12 and 24 h. The levels of MGP mRNA expression were
      quantified using real-time PCR (RT-PCR), and the levels of protein expression
      were characterized by Western blot. RESULTS: MGP was expressed rapidly and
      intensively following exposure to COM and was time-dependent with exposure to
      oxalate. CONCLUSION: Our results have given a profile of MGP expression in renal
      tubular epithelial cells exposed to oxalate and crystals and provided support for
      an association between MGP and kidney stones. Further investigations on the
      mechanism of the MGP in the process of crystal-cell interaction may be important
      in the future.

PMID- 20689250
TI  - Prevalence of Merkel cell polyomavirus among Swiss Merkel cell carcinoma
      patients.
AB  - BACKGROUND: Merkel cell carcinoma (MCC) is a malignant neuroendocrine neoplasm
      which shares structural and immunohistochemical features with neuroectodermally
      derived cells. One hypothesis claims that it arises from Merkel cells, highly
      innervated neuroendocrine cells involved in mechanoreception in the skin. The
      incidence rate of this cancer increases with age and sun exposure as well as
      after immunosuppression. Recently, the clonal integration of a newly identified
      polyomavirus called Merkel cell polyomavirus (MCPyV) was reported in up to 80% of
      MCC tissue. Here we report the incidence rate of MCPyV in MCC patients in
      Switzerland. METHODS: We performed polymerase chain reaction in a collection of
      32 samples obtained from pathology institutes around Switzerland. We used three
      different published primer sets. As control groups we used 7 squamous cell
      carcinoma samples and 11 normal skin samples. CONCLUSIONS: We detected viral DNA
      in 20 out of 30 cases of MCC and in 0 out of 19 control samples. The presence of
      viral DNA in 66.6% of our MCC tissue specimens confirms the high prevalence of
      MCPyV in MCC patients described in American, German, French and Hungarian patient
      collections.

PMID- 20689251
TI  - 6th Fabisch symposium for cancer research and molecular cell biology--enzymes in
      physiology and pathogenesis: signaling by secretases.

PMID- 20689252
TI  - The association of exposure to lead, mercury, and selenium and the development of
      amyotrophic lateral sclerosis and the epigenetic implications.
AB  - Metal exposures are an intriguing potential culprit in the cause of sporadic
      amyotrophic lateral sclerosis (ALS). For one, there are numerous case reports
      linking different metals to an ALS phenotype. Furthermore, some investigators
      have demonstrated higher levels of certain metals in the blood, bone,
      cerebrospinal fluid, urine, or spinal cords of patients with ALS compared to
      controls. There are also many case-control studies looking at the possible
      association of certain metals with the development of ALS. We have reviewed the
      relevant literature regarding metal exposures and the risk of developing ALS. We
      found that many different metals have been implicated as having a role in ALS,
      but there is more literature investigating the role of lead than any other metal.
      Despite many studies, the role, if any, of this metal in the pathogenesis of ALS
      remains unclear. Similarly, other metals either have inconclusive, conflicting,
      or insufficient results in order to make a definitive conclusion. One explanation
      for these findings is that metal exposures alone are insufficient for the
      development of ALS. Perhaps an interaction between the metal exposure and an
      individual's genetic makeup is required to produce epigenetic changes that
      ultimately lead to ALS.

PMID- 20689253
TI  - Bladder preservation strategy based on combined therapy in patients with muscle
      invasive bladder cancer: management and results at long-term follow-up.
AB  - OBJECTIVE: To evaluate a bladder preservation strategy in patients with either
      muscle-invasive bladder cancer (MIBC) or development of MIBC cancer due to
      progression of non-muscle-invasive bladder cancer (NMIBC). METHODS: Between
      October 1982 and March 1998, 48 patients (mean age 61 years, range 45-75) with
      MIBC (T2a-b and T3a) were treated using transurethral resection followed by three
      cycles of systemic chemotherapy. 42 patients (87.5%) had primary MIBC and 6
      (12.5%) had MIBC subsequent to NMIBC. After chemotherapy, 39 patients (81.25%)
      achieved complete remission and 4 (8.3%) partial remission. RESULTS: With a
      median follow-up of 98.5 months (13-246), the overall survival of the 48 patients
      was 62.6%. The cancer-specific survival (CSS) of the 39 patients with complete
      remission was 80.8%. Among the 39 patients with complete remission, 19 had
      invasive recurrence during follow-up with a CSS of 53.2%; by comparison, among
      patients with preserved bladders, CSS was 72.1% (p = 0.046). Predictive factors
      analysed were age, sex, tumour size >3 cm, grade, associated carcinoma in situ
      (CIS), number of tumours and number of previous recurrences. In multivariate
      analysis only tumour size and CIS were significant predictive factors for
      progression after preservation. Of the 6 patients with MIBC after NMIBC, 3 (50%)
      had no remission and underwent cystectomy and 15 patients (38.6%) had NMIBC
      recurrences during follow-up. CIS and high-grade tumours were treated with
      bacillus Calmette-Guerin. A bladder preservation rate of 81% and a CSS rate of
      89% were obtained in the group with NMIBC recurrences. CONCLUSIONS: Conservative
      management of MIBC cancer is a feasible alternative to cystectomy in selected
      cases. Patients with MIBC after progression of primary NMIBC are not good
      candidates for a bladder preservation approach. NMIBC recurrences after bladder
      preservation in patients with MIBC respond to transurethral resection and
      bacillus Calmette-Guerin instillations.

PMID- 20689254
TI  - Ecthyma-gangrenosum-like bullous pemphigoid.
AB  - Bullous pemphigoid (BP) is a chronic, autoimmune, subepidermal blistering skin
      disease with varied clinical presentations. Diagnosis is based on the clinical
      picture, histopathological findings, and direct and indirect immunofluorescence
      studies. In unclear cases, ELISA or Western blot analysis helps to establish a
      definite diagnosis by the detection of immunoglobulin G autoantibodies specific
      for the hemidesmosomal BP antigens BP230 and BP180. We report 3 cases of BP with
      an as yet not characterized, distinctive ecthyma-gangrenosum-like presentation.
      Patients were female, above 80 years of age, physically immobile, and skin
      lesions showed truncal localization and bacterial colonization. Factors
      contributing to physical immobility were a high body mass index, psychiatric
      disease, sedative medication and rheumatic disease. The clinical picture
      resembled ecthyma gangrenosum but lacked systemic infection with Pseudomonas
      aeruginosa. Lesional bacteriological studies revealed Staphylococcusaureus and/or
      P. aeruginosa. Diagnosis proved challenging in all cases. Suspicion has to be
      high, and repeated diagnostic procedures and additional laboratory studies may be
      necessary to establish a definitive diagnosis of BP. In summary, we propose this
      combination of truncal ecthyma-gangrenosum-like lesions with bacterial
      colonization in the context of older age and immobility as a clinically distinct
      presentation or variant of BP.

PMID- 20689255
TI  - Effects of antenatal steroid therapy on neurodevelopment in an IUGR mouse model.
AB  - BACKGROUND/OBJECTIVE: To investigate the neurodevelopmental response in postnatal
      mice secondary to antenatal steroid treatment in association with maternal
      protein restriction. METHODS: C57BL/6N pregnant mice (n = 24; 4 per treatment
      group) were administered control (C) or protein-restricted (PR) diets and
      subjected to daily subcutaneous injection stress during late gestation (E10-E17)
      with either 100 microl/kg of dexamethasone sodium phosphate in normosaline (C
      D/S, PR-D/S) or normosaline alone (C-S, PR-S). Non-treatment groups were also
      included (C, PR). Brain samples of pups were collected on postnatal day 7 and
      analyzed by immunohistochemistry and qRT-PCR. RESULTS: Neonatal weights in the
      treatment groups were smaller than their counterparts in the C group, but there
      were no significant differences in brain size. Immunohistochemical evaluation of
      neuroglial cells revealed a pronounced effect of protein restriction on
      oligodendrocytes and oligodendrocyte precursor cells with distinct fetal
      responses to stress and dexamethasone. Further evaluation using quantitative RNA
      analysis showed significant activation of Galr1, Galr2, Igfbp-1, Igfbp-3, Igfbp
      6, and Fgf2 by 1- to 2.5-fold in the PR-D/S group and by much higher increments,
      1- to 10.5-fold, in the PR-S group. CONCLUSION: This preliminary investigation
      revealed the possible role of dexamethasone in further increasing vulnerability
      to cell damage in injury-prone neuroglial cells. The distribution of key glial
      markers and the overexpression of several neurotrophic factors depicted ongoing
      cellular adaptation.

PMID- 20689256
TI  - 'Bullous' pemphigoid: what are you? Urgent need of definitions and diagnostic
      criteria.

PMID- 20689257
TI  - Clinical and genetic knowledge and attitudes of patients with myotonic dystrophy
      type 1.
AB  - AIMS: The goal was to assess clinical and genetic knowledge and attitudes in
      patients affected by myotonic dystrophy type 1 (DM1). METHODS: Two hundred
      patients with molecular confirmation of the diagnosis of DM1 completed a multi
      choice questionnaire. DM1 patients' knowledge and views were compared to
      clinically normal DM1 noncarriers (n = 264) and controls (n = 1,474). RESULTS:
      Knowledge of the DM1 mode of inheritance was better in noncarriers than in
      patients (p < 0.001). Noncarriers were more aware than DM1 patients of the common
      clinical characteristics of DM1 such as limitations in physical activities and
      problems related to employment, schooling, activities of daily living,
      parenthood, peer relationships, and personality (p < 0.001). Compared to
      controls, DM1 patients felt less informed about the availability of clinical
      genetic services (p < 0.05) and new genetic technologies (p < 0.001). Among
      patients, logistic regression revealed that each additional year of education (p
      < 0.05) and each additional 100 CTG repeats (p < 0.01), respectively, increased
      and decreased the odds of knowing the DM1 mode of inheritance by about 23% and
      18% respectively, independently of age, age at onset of symptoms, gender,
      severity of muscular impairment, and intellectual quotient. CONCLUSIONS: DM1
      patients' genetic knowledge is significantly dependent of the level of education
      and the number of CTG repeats. Healthcare providers should be aware of this
      situation in order to adjust counselling and education accordingly.

PMID- 20689258
TI  - Case report and review: prenatal diagnosis of congenital megalourethra.
AB  - Megalourethra is a rare congenital anomaly characterized by dilatation of the
      penile urethra which causes functional obstruction of the lower urinary system.
      We present a case of congenital megalourethra diagnosed prenatally.
      Transabdominal sonography revealed a male fetus with bilateral hydroureter,
      hydronephrosis, dilated bladder and normal amniotic fluid. The fetal penis was
      enlarged and the penile urethra was dilated with ballooning at the distal end.
      The urethral meatus was identified. The fetus was delivered at term with a
      favorable outcome.

PMID- 20689259
TI  - Urodynamic impact of acute urinary retention in patients with benign prostatic
      hyperplasia: a 2-year follow-up after transurethral resection of the prostate.
AB  - INTRODUCTION: Benign prostatic hyperplasia (BPH) may ultimately result in acute
      urinary retention (AUR). This study was performed to assess the impact of
      transurethral resection of the prostate (TURP) on urodynamic parameters in
      patients with BPH using pre- and postoperative pressure-flow studies (PFS) and
      compare those between patients with and without preoperative AUR. PATIENTS AND
      METHODS: 78 patients underwent TURP because of symptoms due to BPH and were
      evaluated preoperatively and at follow-up after a mean +/- SD of 27 +/- 11.5
      months by the International Prostate Symptom Score and PFS. RESULTS: 32% of
      patients were admitted with AUR. The clinical and principal urodynamic parameters
      exhibited statistically significant improvement reaching normal values after TURP
      in most patients. Comparing patients with and without AUR, the bladder compliance
      significantly increased (p = 0.0013) from the preoperative period to follow-up
      only in patients with preoperative AUR. The minimal opening pressure decreased
      significantly more (p = 0.0077) from the preoperative period to follow-up in the
      non-AUR group. Patients older than 80 years and younger patients showed
      comparable results. CONCLUSIONS: TURP leads to a sustained and age-independent
      improvement of clinically relevant PFS parameters in patients with BPH. Patients
      with preoperative AUR had comparable symptomatic, but an impaired urodynamic
      outcome compared to patients without AUR.

PMID- 20689260
TI  - Bone-marrow-derived mesenchymal stem cell transplantation enhances closing
      pressure and leak point pressure in a female urinary incontinence rat model.
AB  - PURPOSE: The purpose of this study was to determine whether periurethral
      injection of allogenic mesenchymal stem cells (MSCs) could increase the leak
      point pressure (LPP) in a rat model of stress urinary incontinence. MATERIALS AND
      METHODS: Female Sprague-Dawley rats (230-240 g, n = 30) were divided into 3
      groups: sham operation (group C), saline-treated (group S) and MSC-treated (group
      M). Bilateral pudendal nerve dissection followed by normal saline or MSC
      injection on both sides of the urethra was done. LPP and closing pressure (CP)
      testing was performed after the treatment. The specific markers for smooth muscle
      cells in the transplantation sites of the urethra were determined. RESULTS: Both
      the LPP and CP were significantly lower in group S than controls. However, these
      were restored to the control values in group M (p < 0.05). The LPPs of groups C,
      S and M were 29.1 +/- 2.1, 22.0 +/- 2.2 and 43.1 +/- 3.2 cm H(2)O, respectively.
      The CPs of groups C, S and M were 27.1 +/- 3.1, 21.1 +/- 3.2, and 32.1 +/- 2.1 cm
      H(2)O, respectively. The injected MSCs stained positive for muscle-specific
      markers. CONCLUSION: This study suggests that MSCs might differentiate into
      muscle lineage cells and may contribute to the repair of damaged muscle tissue.

PMID- 20689261
TI  - The clinical and molecular heterogeneity of 17betaHSD-3 enzyme deficiency.
AB  - 17-beta-Hydroxysteroid dehydrogenase type 3 (17betaHSD-3) deficiency is a rare,
      but frequently misdiagnosed autosomal recessive cause of 46,XY disorder of sex
      development (DSD). 17betaHSD-3 enzyme is present almost exclusively in the testes
      and converts Delta4-androstenedione (Delta4) to testosterone (T). The diagnosis
      can be easily missed in early childhood as the clinical presentation may be
      subtle. Any young girl with an inguinal hernia, mild clitoromegaly, single
      urethral opening or urogenital sinus should raise suspicion. If not diagnosed
      early, patients present with severe virilization and primary amenorrhea in
      adolescence and may undergo a change from a female to male gender role. A low
      T/Delta4 ratio on baseline or hCG (human chorionic gonadotropin)-stimulated
      testing is suggestive of 17betaHSD-3 deficiency. The diagnosis can be confirmed
      with molecular genetic studies. This review summarizes the clinical
      presentations, reported mutations, diagnosis, treatment and clinical course of
      this disorder. The Arg80 site in exon 3 is the most common location of repeated
      mutations and can be considered a hot spot in certain Arab populations.

PMID- 20689262
TI  - Comparative analysis by chromosome painting of the sex chromosomes in arvicolid
      rodents.
AB  - Sex chromosome evolution in mammals has been extensively investigated through
      chromosome-painting analyses. In some rodent species from the subfamily
      Arvicolinae the sex chromosomes contain remarkable features such as giant size, a
      consequence of heterochromatic enlargement, or asynaptic behaviour during male
      meiosis. Here, we have made a comparative study of the sex chromosomes in 6
      arvicolid species using different probes from the X and Y chromosomes of 3
      species, in order to gain knowledge about intra- or interspecific preservation of
      euchromatic regions. Our results clearly reveal poor conservation of the
      euchromatic region of the Y chromosome within these species, while the
      euchromatin on the X chromosome is extremely well preserved. Furthermore, we
      detected no clear correlation between the synaptic/asynaptic behaviour of the sex
      chromosomes, and the presence or absence of sequence homology within their
      euchromatic regions. Notably, our study has shown a new relationship between the
      giant sex chromosomes of 2 species, Microtus agrestis and Microtus cabrerae, that
      is, both X and Y share a novel region of common sequences in the euchromatin that
      is not present in the other species analysed. This interspecific euchromatic
      conservation, limited to the giant sex chromosomes, could point towards a common
      evolutionary origin for the heterochromatic enlargement process that has
      characterized the evolution of the sex chromosomes in some arvicolid species.

PMID- 20689263
TI  - Neural tube defects: review of experimental evidence on stem cell therapy and
      newer treatment options.
AB  - The failure of closure of the neural tube during development leads to
      malformations called neural tube defects (NTDs). The most common neural
      malformations in humans include anencephaly, encephalocele, exencephaly,
      craniorachischisis spina bifida with or without myelomeningocele,
      lipomyeloschisis, lipomyelomeningocele, meningocele and myelocystocele. Current
      preventive strategies are mainly based on pharmacologic/folic acid
      supplementation. However, stem cell-based and other combination approaches may
      emerge as potential treatment options for NTDs. This review provides an account
      of experimental evidence on stem cell therapy and newer treatment options for
      NTDs which have become available in recent years.

PMID- 20689264
TI  - List of drugs in development for neurodegenerative diseases: update June 2010.

PMID- 20689265
TI  - Pancreatic cystic endocrine tumors: a different morphological entity associated
      with a less aggressive behavior.
AB  - BACKGROUND: Cystic pancreatic endocrine tumors (CPETs) are rare lesions and their
      biological features have been scarcely investigated. AIM: To compare clinical and
      pathological features of resected non-functioning sporadic CPETs (NF-CPETs) with
      solid pancreatic endocrine tumors (SPETs) in a single-institution experience.
      METHODS: All patients with a pathologically confirmed diagnosis of sporadic non
      functioning pancreatic endocrine tumors who underwent curative resection between
      1990 and 2008 were included. A comparison of demographic, clinical and
      pathological characteristics between CPETs and SPETs was made. Univariate and
      multivariable analyses were performed to identify preoperative predictors of
      carcinoma (non-functioning pancreatic endocrine carcinoma). RESULTS: Twenty-one
      (11.5%) patients with a histological diagnosis of NF-CPET were identified. The
      median age was 60 years (IQR 46.5-73.5 years) and a diagnosis of carcinoma (non
      functioning pancreatic endocrine carcinoma) was made in 3 (14.3%) cases. In the
      comparison with NF-SPETs, no differences were found in terms of gender (p =
      0.75), age (p = 0.81), presenting symptoms (p = 0.43), localization of the tumors
      (p = 0.46) and type of resection (p = 0.31). The incidence of non-functioning
      pancreatic endocrine carcinoma was significantly lower in the NF-CPET versus the
      NF-SPET group (14.3 vs. 40.4%, p = 0.04). By univariate analysis, preoperative
      predictors of non-functioning pancreatic endocrine carcinoma included the
      presence of symptoms (OR 3.96, 95% CI 2.06-7.63) and an increase in the absolute
      value of radiological diameter (OR 1.05, 95% CI 1.03-1.07). A cystic morphology
      of the lesion turned out to be a negative predictor of carcinoma (OR 0.25, 95% CI
      0.70-0.87). These results were confirmed by multivariable analysis. CONCLUSIONS:
      NF-CPETs have a measurable propensity to be benign. In those patients affected by
      small and asymptomatic NF-CPET a more conservative surgical approach or a follow
      up policy could be considered.

PMID- 20689266
TI  - Androgen replacement therapy in late-onset hypogonadism: current concepts and
      controversies - a mini-review.
AB  - BACKGROUND: Normal testicular function is essential for the maintenance of male
      physical strength and behaviour irrespective of age. A new term of late-onset
      hypogonadism (LOH) has been coined for the condition of decreased testosterone
      (T) and hypogonadal symptoms in ageing men. OBJECTIVE: The most important
      testicular hormone, T, is responsible for the gender-specific androgenic-anabolic
      effects in men. Testicular T production remains stable until around the age of 40
      years after which it declines by 1-2% annually. Despite this age-related decline,
      serum T levels in most older men remain within the reference range of younger
      men. The decreasing androgen levels are paralleled by well-defined objective
      biological and nonspecific subjective signs and symptoms of ageing. Because these
      symptoms are similar to those observed in young men with documented hypogonadism,
      androgen replacement therapy (ART) has been considered a logical way to treat
      them. METHODS: A thorough review of the existing literature was performed to
      evaluate the current concepts and controversies related to ageing men and ART.
      RESULTS: Although it is intuitively logical that the symptoms of LOH are due to
      the ageing-related deficiency of T, and that they can be reversed by ART, the
      evidence for this is still variable and often weak. In particular, evidence-based
      information about long-term benefits and risks of ART in ageing men is largely
      missing. CONCLUSIONS: Despite widespread use, evidence-based proof for the
      objective benefits and side effects of ART of elderly men is still scanty, and
      such treatments should be considered experimental.

PMID- 20689267
TI  - Diagnosis of acute pulmonary embolism by endobronchial ultrasound as an
      incidental finding.

PMID- 20689268
TI  - Left atrial mass demonstrated during endobronchial ultrasound session.

PMID- 20689269
TI  - Lessons from a case of oromandibular mucormycosis treated with surgery and a
      combination of amphotericin B lipid formulation plus caspofungin.
AB  - A rare case of oromandibular Rhizopus oryzae infection is described in a 55-year
      old woman with acute myeloid leukaemia and decompensated diabetes mellitus. The
      infection developed during induction chemotherapy when the patient was
      neutropenic. She was treated with a combination of amphotericin B lipid
      formulation and caspofungin plus surgery. Debridement surgery included excision
      of the lower lip, chin, floor of the mouth, a portion of the tongue, as well as
      mandibular resection at the level of the horizontal branches. Eight weeks of
      combined antifungal therapy were followed by secondary prophylaxis with
      amphotericin B lipid formulation during consolidation chemotherapy after
      achieving complete response of both leukaemia and mucormycosis. Reconstructive
      surgery was carried out including insertion of a new biomaterial porous
      mandibular prosthesis, which showed excellent functionality after long-term
      follow-up, followed by several plastic surgery procedures once good tolerability
      and no adverse effects of the prosthesis were observed. This case shows that a
      well-coordinated multidisciplinary approach is critical to increase the chances
      of clinical success in this life-threatening infection.

PMID- 20689270
TI  - Unsuccessful dasatinib therapy in a refractory patient with chronic lymphocytic
      leukemia.

PMID- 20689271
TI  - Altered renal expression of angiotensin II receptors, renin receptor, and ACE-2
      precede the development of renal fibrosis in aging rats.
AB  - BACKGROUND: The susceptibility to fibrosis and progression of renal disease is
      mitigated by inhibition of the renin-angiotensin system (RAS). We hypothesized
      that activation of the intrarenal RAS predisposes to renal fibrosis in aging.
      METHODS: Intrarenal expression of angiotensin II type 1 (AT(1)R), type 2
      (AT(2)R), and (pro)renin receptors, ACE and ACE-2, as well as pro- and
      antioxidant enzymes were measured in 3-month-old (young), 14-month-old (middle
      aged), and 24-month-old (old) male Sprague-Dawley rats. RESULTS: Old rats
      manifested glomerulosclerosis and severe tubulointerstitial fibrosis with
      increased fibronectin and TGF-beta expression (7-fold). AT(1)R /AT(2)R ratios
      were increased in middle-aged (cortical 1.6-fold, medullary 5-fold) and old rats
      (cortical 2-fold, medullary 4-fold). Similarly, (pro)renin receptor expression
      was increased in middle-aged (cortical 2-fold, medullary 3-fold) and old
      (cortical 5-fold, medullary 3-fold) rats. Cortical ACE was increased (+35%) in
      old rats, whereas ACE-2 was decreased (-50%) in middle-aged and old rats. NADPH
      oxidase activity was increased (2-fold), whereas antioxidant capacity and
      expression of the mitochondrial enzyme manganese superoxide dismutase (cortical 
      40%, medullary -53%) and medullary endothelial nitric oxide synthase (-48%) were
      decreased in old rats. CONCLUSION: Age-related intrarenal activation of the RAS
      preceded the development of severe renal fibrosis, suggesting that it contributes
      to the increased susceptibility to renal injury observed in the elderly.

PMID- 20689272
TI  - Hybrid renal replacement treatment in acute pulmonary edema with acute kidney
      injury following multiple wasp stings: a report of 3 cases.

PMID- 20689273
TI  - Fulminant meningococcal sepsis: localized outbreak of three patients treated with
      therapeutic plasma exchange by membrane filtration.

PMID- 20689274
TI  - Prior bare metal stent restenosis as a predictor for subsequent restenosis: the
      lightning often strikes twice.

PMID- 20689275
TI  - A history of prior bare metal stent restenosis is associated with major adverse
      cardiac events in subsequent bare metal stenting of de novo coronary lesions.
AB  - OBJECTIVE: To investigate the risk of major adverse cardiac events (MACE) in
      patients with a history of bare metal stent (BMS) restenosis who undergo
      subsequent bare metal stenting of a geographically distinct, de novo coronary
      lesion. METHODS: We conducted a retrospective review of 72 BMS procedures
      performed in geographically distinct, de novo coronary lesions in patients with a
      history of previous BMS placement at least 3 months prior to the second, index
      stent procedure. Patients with a history of in-stent restenosis (ISR) were
      compared with those who had no ISR in their initial stent. RESULTS: Restenosis in
      the initial BMS was associated with a significant increase in MACE after
      placement of the index BMS (OR 20.0, 95% CI 3.86-103.58, p < 0.0001). This
      association was independent of traditional clinical and angiographic risk factors
      for restenosis. CONCLUSIONS: Restenosis of a previously placed BMS is strongly
      associated with MACE after placement of a subsequent BMS in a de novo coronary
      lesion.

PMID- 20689276
TI  - Myocardial calcification and hypertension following chronic renal failure and
      ameliorative effects of furosemide and captopril.
AB  - OBJECTIVES: The aim of this study was to prevent metastatic myocardial
      calcification and hypertension following chronic renal failure (CRF). METHODS: A
      total of 50 male Sprague-Dawley rats were allocated to one of five groups: the
      control group (sham), the NxNT group (nephrectomized rats receiving no
      treatment), the NxFuro group (nephrectomized rats treated with furosemide), the
      NxCap group (nephrectomized rats treated with captopril) and the NxFuroCap group
      (nephrectomized rats treated with furosemide and captopril). Surgery (5/6
      nephrectomy) was performed to induce CRF. Oral treatment with furosemide (20
      mg/kg) and/or captopril (0.05 mg/kg) was given twice daily for 5 weeks.
      Parameters were studied after 5 weeks. RESULTS: In the NxNT group, arterial blood
      pressure was significantly increased compared with the controls. Monotherapy with
      furosemide or captopril and both in combination maintained blood pressure to near
      or below control. Myocardial and remnant-kidney calcification was detected in
      NxNT rats, but calcification was absent in the NxFuroCap rats. Cardiac
      hypertrophy and fibrosis was observed in the NxNT group but not in treatment
      groups. Both plasma inorganic phosphate and Ca(2+) significantly increased in the
      NxNT group, but the difference was not significant in the treatment groups.
      CONCLUSION: Furosemide, either alone or in combination with captopril, is capable
      to prevent myocardial calcification, cardiac hypertrophy and hypertension,
      maintaining blood Ca(2+) and phosphate levels by slowing CRF.

PMID- 20689277
TI  - Worsening renal function defined as an absolute increase in serum creatinine is a
      biased metric for the study of cardio-renal interactions.
AB  - OBJECTIVES: Worsening renal function (WRF) during the treatment of decompensated
      heart failure, frequently defined as an absolute increase in serum creatinine
      >or=0.3 mg/dl, has been reported as a strong adverse prognostic factor in several
      studies. We hypothesized that this definition of WRF is biased by baseline renal
      function secondary to the exponential relationship between creatinine and renal
      function. METHODS: We reviewed consecutive admissions with a discharge diagnosis
      of heart failure. An increase in creatinine >or=0.3 mg/dl (WRF(CREAT)) was
      compared to a decrease in GFR >or=20% (WRF(GFR)). RESULTS: Overall, 993
      admissions met eligibility. WRF(CREAT) occurred in 31.5% and WRF(GFR) in 32.7%.
      WRF(CREAT) and WRF(GFR) had opposing relationships with baseline renal function
      (OR = 1.9 vs. OR = 0.51, respectively, p < 0.001). Both definitions had similar
      unadjusted associations with death at 30 days [WRF(GFR) OR = 2.3 (95% CI 1.1
      4.8), p = 0.026; WRF(CREAT) OR = 2.1 (95% CI 1.0-4.4), p = 0.047]. Controlling
      for baseline renal insufficiency, WRF(GFR) added incrementally in the prediction
      of mortality (p = 0.009); however, WRF(CREAT) did not (p = 0.11). CONCLUSIONS:
      WRF, defined as an absolute change in serum creatinine, is heavily biased by
      baseline renal function. An alternative definition of WRF should be considered
      for future studies of cardio-renal interactions.

PMID- 20689278
TI  - Evaluation of operative risk in elderly patients undergoing aortic valve
      replacement: the predictive value of operative risk scores.
AB  - OBJECTIVES: An increasing number of elderly patients develop aortic valve disease
      requiring surgery. Operative risk scores are currently used to identify patients
      at high operative risk who may benefit from interventional treatment options. The
      aim of this study was to analyze the predictive value of these risk scores in
      geriatric patients undergoing aortic valve replacement. METHODS: We reviewed data
      of 1,245 elderly patients who underwent aortic valve replacement with or without
      additional bypass surgery from 2000-2007. Patient data were derived from a
      prospective registry at the Department of Cardiac Surgery at Albertinen-Hospital
      in Hamburg, Germany. RESULTS: Hospital mortality was 2.56% in isolated valve
      replacement and 3.38% in patients who had additional bypass surgery (p = ns). Age
      >80 years (OR 1.7; 95% CI: 1.3-3.3) and renal failure (OR 1.6; 95% CI: 1.1-2.5)
      were significantly associated with in-hospital death. All scores overestimated
      operative mortality. The median logistic EuroSCORE was 11.56% (interquartile
      range: 7.01-18.96), median STS score 13.9% (10.3-16.2); and median Ambler score
      7.2% (4.1-9.3). There was a significant correlation of the STS score with
      operative mortality (Spearman's rank coefficient: 0.68), but not with EuroSCORE
      (Spearman's rank coefficient: 0.11) or Ambler score (Spearman's rank coefficient:
      -0.17). CONCLUSION: Current risk scores overestimate operative risk in geriatric
      patients undergoing aortic valve replacement substantially. Of the risk scores
      evaluated, only STS score correlated significantly with operative mortality.
      Operative risk scores aimed specifically at geriatric patients may be necessary
      to accurately identify patients at high operative risk who benefit from non
      surgical treatment options.

PMID- 20689279
TI  - Increased levels of soluble LR11 in cerebrospinal fluid of patients with
      Alzheimer disease.
AB  - BACKGROUND: Recent genetic and pathological studies have suggested that a
      lipoprotein receptor, LR11, is intricately implicated in the pathogenesis of
      Alzheimer disease (AD). We have recently established a novel sandwich ELISA,
      which enabled the sensitive quantification of a soluble LR11 (sLR11). By this
      ELISA, we attempted to determine the difference in the levels of CSF sLR11 in AD
      patients. METHODS: We examined CSF from 29 AD patients, 20 frontotemporal lobar
      degeneration patients and 27 age-matched control subjects. The CSF sLR11 level as
      well as the levels of tau and beta-amyloid42 (Abeta42) were determined by
      sandwich ELISA. RESULTS: The CSF tau level and tau/Abeta42 ratio were
      significantly increased (p < 0.01) in the AD patients. The CSF sLR11 level in the
      AD patients was significantly higher (p < 0.01) than that of the frontotemporal
      lobar degeneration patients and the controls. The APOE-epsilon4-positive AD
      patients have higher sLR11 levels than the APOE-epsilon4-negative patients (p <
      0.01). CONCLUSIONS: These results suggest that the quantification of CSF sLR11
      may serve as a biomarker of AD, although the diagnostic value for individual
      patients is limited. An elevated CSF sLR11 level in AD patients may be relevant
      to AD pathogenesis.

PMID- 20689280
TI  - Emotional and psychological distress of persons involved in the care of patients
      with Alzheimer disease predicts falls and fractures in their care recipients.
AB  - BACKGROUND/AIMS: Elderly patients with dementia have a higher risk of falls and
      fractures as compared to cognitively intact elderly subjects. To investigate
      whether psychological distress of the caregiver might predispose older persons
      with Alzheimer disease (AD) to falls and fractures, we performed a prospective
      cohort study. METHODS: A consecutive series of 110 subjects with dementia
      underwent baseline and follow-up clinical and functional evaluations. The burden
      of the caregivers was recorded at baseline. Any intervening fall or fracture was
      ascertained at the 1-year follow-up. RESULTS: The caregiver burden was
      significantly higher in persons involved in the care of patients with AD who
      subsequently fell. In a multivariate regression model, the caregiver burden score
      predicted falls and fractures. CONCLUSION: Part of the increased risk of falls
      and fractures in AD might be due to the distress of caregivers, a factor
      potentially amenable to treatment.

PMID- 20689281
TI  - Low cancer rates among patients with dementia in a population-based register
      study in Sweden.
AB  - BACKGROUND: Some studies have suggested a lower incidence of cancer in patients
      with dementia. We studied this further for 18 cancer types in population-based
      registers. METHODS: In 19,756 cases and in 147,324 age- and sex-matched controls
      a diagnosis of dementia was studied 9-45 months prior to the diagnosis of cancer.
      RESULTS: Overall a diagnosis of dementia was significantly less common among the
      cancer cases (risk ratio, RR = 0.60; 95% CI = 0.52-0.69). CONCLUSION: The study
      confirms previous findings that patients with dementia have a lower risk of
      cancer. Because the effect was seen for all tumour types and especially for
      patients older than 70 years and since the deficit was more pronounced for
      patients with tumours situated within the body, the data suggest that
      malignancies are underdiagnosed for persons with dementia.

PMID- 20689282
TI  - Hysterectomy, oophorectomy and risk of dementia: a nationwide historical cohort
      study.
AB  - BACKGROUND: This study aimed to determine whether there is an association between
      hysterectomy and dementia. METHODS: All female Danish residents born before 1966,
      alive on their 40th birthday and without a dementia diagnosis prior to 1977 (n =
      2,313,388) were followed from January 1, 1977, or the age of 40, whichever came
      later, until dementia diagnosis, death, emigration or December 31, 2006,
      whichever came first. The relative risks (RR) for developing dementia in women
      with hysterectomy/oophorectomy compared to referent women were calculated.
      RESULTS: Overall, hysterectomy did not increase the risk of dementia. When
      stratified by age at dementia diagnosis, hysterectomy was associated with an
      increased risk for early-onset dementia before the age of 50: hysterectomy alone
      (RR = 1.38, 95% confidence interval (CI) = 1.07-1.78), with unilateral
      oophorectomy (RR = 2.10, 95% CI = 1.28-3.45), with bilateral oophorectomy (RR =
      2.33, 95% CI = 1.44-3.77). The younger the age at hysterectomy/oophorectomy, the
      greater was the risk. CONCLUSIONS: Although statistically significant, the
      association between premenopausal hysterectomy and early-onset dementia is
      uncertain due to study limitations. Premenopausal bilateral oophorectomy is
      associated with a higher risk, suggesting a dose effect of premature estrogen
      deficiency on dementia. The age-dependent effect suggests that the younger brain
      is probably more vulnerable to estrogen deficiency.

PMID- 20689283
TI  - Multi-modal hallucinations and cognitive function in Parkinson's disease.
AB  - BACKGROUND/AIMS: Hallucinations have been linked to a constellation of cognitive
      deficits in Parkinson's disease (PD), but it is not known whether multi-modal
      hallucinations are associated with greater neuropsychological dysfunction.
      METHODS: 152 idiopathic PD patients were categorized based on the presence or
      absence of hallucinations and then were further subdivided into visual-only
      (VHonly; n = 35) or multi-modal (VHplus; n = 12) hallucination groups. All
      participants underwent detailed neuropsychological assessment. RESULTS:
      Participants with hallucinations performed more poorly on select
      neuropsychological measures and exhibited more mood symptoms. There were no
      differences between VHonly and VHplus groups. CONCLUSIONS: PD patients with multi
      modal hallucinations are not at greater risk for neuropsychological impairment
      than those with single-modal hallucinations.

PMID- 20689284
TI  - Neuropsychiatric symptoms underlying caregiver stress and insight in Alzheimer's
      disease.
AB  - OBJECTIVE: Cluster analysis based on Alzheimer's disease (AD) neuropsychiatric
      profile demonstrated validity on caregiver burden, nursing-home placement and
      survival. The aims of our study were to explore the validity of this approach on
      caregiver burden, lack of insight and cognitive impairment and to examine the
      impact of neuropsychiatric profiles on these variables. METHOD: A data-driven
      approach (two-step cluster analysis) identified groups of patients based on
      similarities of their neuropsychiatric symptom profile, as assessed by the
      Neuropsychiatric Inventory (NPI). ANOVAs and chi(2) tests were used to compare
      groups with regard to continuous and categorical variables. Linear regressions
      tested the relationships between NPI and clinical variables. RESULTS:
      Psychotic/behavioral, depressive and minimally symptomatic clusters differed for
      caregiver burden and lack of insight. Patients in the minimally symptomatic
      cluster showed better insight than those in the depressive cluster. Caregivers of
      the psychotic/behavioral cluster experienced the highest burden. We found
      positive relationships between NPI and lack of insight in the depressive and
      minimally symptomatic clusters and between NPI and caregiver burden in all three
      clusters. Caregiver burden was influenced by the type of symptoms. CONCLUSIONS:
      The cluster analysis was valid for lack of insight and caregiver burden. Symptoms
      predominant on caregiver burden could become targets for therapy.

PMID- 20689285
TI  - Cognitive deterioration rates in patients with Parkinson's disease from
      northeastern China.
AB  - BACKGROUND/AIMS: Cognitive impairment (CI) is common in Parkinson's disease (PD),
      and the cognitive deterioration rate (CDR) is heterogeneous among PD patients.
      However, very few studies have reported on the association of PD features and
      risk factors with rapid CDR. The Montreal Cognitive Assessment (MoCA) is
      considered to be a sensitive and reliable approach to detect mild CI. In the
      present study, we sought to define and compare the cognitive profiles and
      clinical features of PD patients with slow or rapid CDRs, and then to identify
      the PD risk factors associated with rapid CDR. METHODS: A cross-sectional study
      of cognitive rate was performed using the MoCA in a cohort of 73 PD patients and
      41 controls matched for age, sex and education level. RESULTS: The rapid CDR
      group was characterized by older age (58.8 years in slow CDR vs. 64.1 in rapid
      CDR; p = 0.02), later age at disease onset (52.7 vs. 61.7 years; p < 0.001), a
      faster deterioration rate of movement symptoms (UPDRS III increment of 12.8 vs.
      5.9/year; p < 0.001), a higher rate in multiple-domain CI (38.9 vs. 10.8%), and
      generally lower MoCA subscores for the Clock Drawing Test, attention, verbal
      fluency and abstraction. According to the univariate logistic regression model,
      onset age, movement deterioration rate, multiple domains CI and executive
      function CI were risk factors for rapid CDR. However, only the movement
      deterioration rate (p = 0.01) and onset age (p = 0.05) remained independent
      predictors for rapid CDR according to the multivariate logistic regression model.
      CONCLUSIONS: The CI deterioration in a subset of PD patients appears to progress
      more rapidly. Identifying those PD patients may not only help to predict the
      development of PD dementia, but also facilitate therapeutic intervention at early
      disease stages.

PMID- 20689286
TI  - Absolute quantification in proton magnetic resonance spectroscopy is useful to
      differentiate amnesic mild cognitive impairment from Alzheimer's disease and
      healthy aging.
AB  - BACKGROUND/AIMS: Amnesic mild cognitive impairment (aMCI) is thought to represent
      a transitional state between healthy aging and very mild Alzheimer's disease
      (AD). It is very important to diagnose aMCI for early treatment. In order to
      investigate biochemical changes in aMCI, we measured metabolite concentrations
      using proton magnetic resonance spectroscopy ((1)H-MRS) from patients with aMCI
      and compared the results with healthy controls (HCs) and patients with AD.
      METHODS: The subjects were 52 HCs, 70 AD patients and 47 aMCI patients. (1)H-MR
      spectra with single-voxel point-resolved spectroscopy at a short echo time (TE)
      were acquired from 8 volumes of interest in the brain. RESULTS: The bilateral
      hippocampal N-acetylaspartate (NAA) concentrations from aMCI patients showed
      intermediate values, which were lower than those from HC subjects but higher than
      those from AD patients. The patients with aMCI also had lower concentrations of
      NAA than HCs in the bilateral posterior periventricular and deep white matters
      (PDWM) and posterior cingulate gyrus and had lower levels of choline compounds in
      the left posterior PDWM. CONCLUSION: Using a single-voxel (1)H-MRS at a short TE,
      we revealed that absolute quantification is useful to detect the characteristic
      patterns of metabolite concentrations in patients with aMCI as compared with AD
      patients and HCs.

PMID- 20689287
TI  - Gestational and neonatal iron deficiency alters apical dendrite structure of CA1
      pyramidal neurons in adult rat hippocampus.
AB  - The hippocampus develops rapidly during the late fetal and early postnatal
      periods. Fetal/neonatal iron deficiency anemia (IDA) alters the genomic
      expression, neurometabolism and electrophysiology of the hippocampus during the
      period of IDA and, strikingly, in adulthood despite neonatal iron treatment. To
      determine how early IDA affects the structural development of the apical dendrite
      arbor in hippocampal area CA1 in the offspring, pregnant rat dams were given an
      iron-deficient (ID) diet between gestational day 2 and postnatal day (P) 7
      followed by rescue with an iron-sufficient (IS) diet. Apical dendrite morphology
      in hippocampus area CA1 was assessed at P15, P30 and P70 by Scholl analysis of
      Golgi-Cox-stained neurons. Messenger RNA levels of nine cytoplasmic and
      transmembrane proteins that are critical for dendrite growth were analyzed at P7,
      P15, P30 and P65 by quantitative real-time polymerase chain reaction. The ID
      group had reduced transcript levels of proteins that modify actin and tubulin
      dynamics [e.g. cofilin-1 (Cfl-1), profilin-1 (Pfn-1), and profilin-2 (Pfn-2)] at
      P7, followed at P15 by a proximal shift in peak branching, thinner third
      generation dendritic branches and smaller-diameter spine heads. At P30, iron
      treatment since P7 resulted in recovery of all transcripts and structural
      components except for a continued proximal shift in peak branching. Nevertheless,
      at P65-P70, the formerly ID group showed a 32% reduction in 9 mRNA transcripts,
      including Cfl-1 and Pfn-1 and Pfn-2, accompanied by 25% fewer branches, that were
      also proximally shifted. These alterations may be due to early-life programming
      of genes important for structural plasticity during adulthood and may contribute
      to the abnormal long-term electrophysiology and recognition memory behavior that
      follows early iron deficiency.

PMID- 20689288
TI  - Results of 244 consecutive patients with hemorrhoids treated with Doppler-guided
      hemorrhoidal artery ligation.
AB  - AIM: This study was designed to determine the effect of treating hemorrhoids with
      the Doppler-guided hemorrhoidal artery ligation (DG-HAL) procedure. METHODS: From
      June 2005 to March 2008, 244 consecutive hemorrhoidal patients underwent
      hemorroidal artery ligation performed with the DG-HAL system from AMI. All
      patients were evaluated postoperatively with a proctologic examination and
      interview. Further follow-up was performed by telephone with a standardized
      questionnaire. When indicated, patients revisited the clinic for further
      examination and treatment. RESULTS: 244 patients were treated with DG-HAL. The
      mean follow-up time was 18.4 months (range 1.4-37.2). Sixty-seven percent of the
      patients had an improvement of symptoms after one treatment. Fifty-three patients
      (22%) underwent a second procedure because of persisting symptoms. Thirteen
      patients (25%) underwent a second DG-HAL and 40 (75%) underwent rubber band
      ligation. In total, 69% of the patients had a good response using the DG-HAL
      technique. Multivariate logistic regression analysis revealed prolapse to be an
      independent risk factor for persistent symptoms (OR = 2.38, 95% CI 1.10-5.15).
      Patients with grades 3 and 4 hemorrhoids had a higher risk of developing
      recurrent disease (OR = 4.94, 95% CI 0.67-36.42). CONCLUSION: DG-HAL seems to be
      an effective procedure for treating low-grade hemorrhoids. A resection procedure
      should be the treatment for patients with recurrent disease.

PMID- 20689289
TI  - Elevated C-reactive protein and hypoalbuminemia measured before resection of
      colorectal liver metastases predict postoperative survival.
AB  - BACKGROUND: Few studies have investigated whether the Glasgow Prognostic Score
      (GPS), an inflammation-based prognostic score measured before resection of
      colorectal liver metastasis (CRLM), can predict postoperative survival. PATIENTS
      AND METHODS: Sixty-three consecutive patients who underwent curative resection
      for CRLM were investigated. GPS was calculated on the basis of admission data as
      follows: patients with both an elevated C-reactive protein (>10 mg/l) and
      hypoalbuminemia (<35 g/l) were allocated a GPS score of 2. Patients in whom only
      one of these biochemical abnormalities was present were allocated a GPS score of
      1, and patients with a normal C-reactive protein and albumin were allocated a
      score of 0. RESULTS: Significant factors concerning survival were the number of
      liver metastases (p = 0.0044), carcinoembryonic antigen level (p = 0.0191), GPS
      (p = 0.0029), grade of liver metastasis (p = 0.0033), and the number of lymph
      node metastases around the primary cancer (p = 0.0087). Multivariate analysis
      showed the two independent prognostic variables: liver metastases > or =3
      (relative risk 2.83) and GPS1/2 (relative risk 3.07). CONCLUSIONS: GPS measured
      before operation and the number of liver metastases may be used as novel
      predictors of postoperative outcomes in patients who underwent curative resection
      for CRLM.

PMID- 20689290
TI  - Laparoscopy-assisted D2 radical distal gastrectomy for advanced gastric cancer.
AB  - BACKGROUND/AIM: Laparoscopy-assisted surgery has proved useful in the treatment
      of early gastric cancer, but its use in advanced cancer has rarely been studied.
      To investigate the efficacy and advantages of laparoscopy-assisted distal
      gastrectomy (LADG) with D2 dissection of lymph nodes versus conventional open D2
      distal gastrectomy (ODG) in advanced gastric cancer. METHODS: From January 2007
      to June 2008, the clinical data of 66 cases of LADG for advanced gastric cancer
      were compared with that of 69 patients who, during the same period, underwent a
      conventional open radical distal gastrectomy. RESULTS: No patient in the LADG
      group converted to conventional operation with laparotomy. Operative time was
      significantly longer for the LADG group than for the ODG group (266.05 +/- 55.05
      vs. 223.78 +/- 26.79 min). No significant differences were found in the total
      number of retrieved lymph nodes (25.81 +/- 12.53 vs. 27.47 +/- 10.28) between the
      two groups. Patients in the LADG group had less blood loss, shorter time of
      analgesic use, earlier recovery of bowel activity, and shorter postoperative
      hospitalization time. Complication rates were comparable between the two groups.
      CONCLUSIONS: LADG with D2 lymph node dissection is a safe and feasible procedure
      with adequate lymphadenectomy for the treatment of advanced gastric cancer. A
      large-scale prospective randomized trial with a longer follow-up period is needed
      to definitively assess whether LADG is a better alternative than ODG with D2
      lymph node dissection.

PMID- 20689291
TI  - Aggressive treatment approach for cloacogenic carcinoma of the anorectum: report
      from a single cancer center.
AB  - BACKGROUND/AIMS: The prognosis of cloacogenic carcinoma of the anorectum has
      rarely been investigated, and its clinical behavior is supposed to be similar to
      common squamous anal cancers. During the last 10 years, chemoradiation treatment
      (CRT) has been considered the standard of care for anal cancer. METHODS: We
      retrospectively investigated the treatment of cloacogenic cancers treated within
      the framework of a multidisciplinary cancer center team during an 8-year period.
      The medical records of 7 patients affected by cloacogenic carcinoma were
      analyzed. Three patients presented distant metastases at the time of diagnosis.
      CRT using 5-fluorouracil + mitomycin or cisplatin was considered the gold
      standard for those cases amenable to cure. RESULTS: After a mean follow-up time
      of 33 months (range 9-100), disease recurrence or progression was observed in 6
      patients, which caused death in 3 of them. Three- and 5-year actuarial overall
      survival rates were 71 and 48%, respectively. CONCLUSIONS: Our data seem to
      suggest that the cloacogenic origin could present prognostic relevance within the
      wide spectrum of anal cancers. This should be carefully considered when
      submitting patients to aggressive and prolonged treatments. However, this
      hypothesis needs to be confirmed by larger series of this disease.

PMID- 20689292
TI  - Significance of measuring S100A12 and sRAGE in the serum of sepsis patients with
      postoperative acute lung injury.
AB  - BACKGROUND: There is a report that S100A12 is useful as an early marker of acute
      lung injury (ALI). The purpose of this study was to determine whether S100A12 or
      sRAGE is useful as a marker during the development of ALI in postoperative sepsis
      patients. METHODS: The subjects were patients who underwent emergency surgery
      because of sepsis secondary to perforation of the lower gastrointestinal tract.
      We conducted a retrospective study comparing 2 groups of patients: a group of 9
      patients who developed postoperative ALI, the ALI(+) group, and a group of 8
      patients who did not develop postoperative ALI, the ALI(-) group. Their blood
      S100A12, sRAGE, IFN-gamma, WBC count, and CRP values were measured immediately
      after surgery and on postoperative day 1 (D1). RESULTS: The changes in S100A12
      showed significantly higher values immediately postoperatively in the ALI(+)
      group (p < 0.05). The sRAGE values immediately postoperatively were similar, but
      on D1, they were significantly higher in the ALI(-) group (p < 0.05).
      CONCLUSIONS: S100A12 increases in the early stage of development of ALI. sRAGE
      production increases in patients who do not develop ALI.

PMID- 20689293
TI  - Outcome after resection of one hundred gastrointestinal stromal tumors.
AB  - AIMS: To evaluate the outcome after surgical resection in patients with
      gastrointestinal stromal tumors and to determine the factors influencing local
      tumor recurrence or distant metastatic disease after locally complete tumor
      resection (R0). METHODS: Outcomes of 100 patients with primary gastrointestinal
      stromal tumors (GIST) surgically managed between 1997 and 2006 at a single
      institution were reviewed. Univariate and bivariate analyses were used to
      determine factors affecting recurrence-free and tumor-free survival. RESULTS: All
      patients (n = 100) had c-kit-positive GIST. There were 17% (n = 17) very low
      risk, 41% (n = 41) low risk, 19% (n = 19) intermediate risk and 23% (n = 23) high
      risk GIST originating from the stomach, small bowel, colon and rectum. The median
      patient age was 68 years (range 39-92). Seventy-three percent of the patients had
      symptomatic local disease. Most (94%; n = 94) of them underwent R0 resections of
      their primary tumor. R0 resection was significantly associated with a lower tumor
      related mortality rate (p = 0.0001). The patients with recurrence/metastases had
      significantly larger tumors (p = 0.0017) and a mitotic index higher than 5/50 HPF
      (p = 0.0001). Seven of 20 patients from the high-risk group and 2 of 7 patients
      with metastatic disease developed local recurrence or further metastatatic tumor
      spread following R0 resection. CONCLUSION: Surgical removal continues to be the
      mainstay of GIST treatment. R0 resection, tumor size and mitotic index are
      significant prognostic factors. Overall, more than 30% of the patients with high
      risk GIST develop local recurrences and distant metastases despite R0 resection.
      Additional molecular pathological markers are needed to yield a more accurate
      tumor profile and to thus achieve a better predictability of the biological
      behavior of GIST.

PMID- 20689294
TI  - Neurophysiologic investigation of anal function following double stapling
      anastomosis.
AB  - BACKGROUND AND AIM: Manual dilatation of the anal sphincter and transanal
      introduction of the circular stapling device are required for intraluminal
      stapling anastomosis. This procedure has been regarded as one of the causes of
      postoperative evacuatory disorder in low anterior resection. However, there has
      been no evidence of this matter. Therefore, we conducted this study to clarify
      the impact of the procedure of stapling anastomosis on postoperative anal
      function. METHODS: Twenty-five cases with sigmoid colon cancer underwent
      potentially curative sigmoid colectomy with stapling anastomosis (ST group) and
      20 cases with hand-sewn anastomosis (non-ST group). The patients were questioned
      regarding the daily frequency of bowel movement, the presence of urgency and
      soiling, and Wexner's incontinence score. Anorectal manomatry and pudendal nerve
      terminal motor latency were also evaluated. The patients' questionnaire and
      physiologic examinations were prospectively obtained before, and 1 and 6 months
      after the operation. RESULTS: Postoperative bowel habit was graded as satisfied
      in 92% (23/25 patients) in the ST group and 90% (18/20 patients) in the non-ST
      group. There was no significant difference between the 2 groups in terms of
      presence of fecal incontinence, discrimination of gas and stool, and daily
      frequency of bowel movement. In anal manometry, there was no significant
      difference between the 2 groups regarding the resting and squeezing anal canal
      sphincter pressures at 1 and 6 months postoperatively. Pudendal nerve terminal
      motor latency showed their latency from 2.0 to 2.5 ms throughout the periods, and
      there was no difference between the 2 groups before, and 1 and 6 months after the
      operation. CONCLUSION: Stapling anastomosis does not affect anal function in the
      early postoperative period.

PMID- 20689295
TI  - Significance of preoperative evaluations of tumor necrosis factor-alpha, the
      granulocyte/lymphocyte ratio and their correlation with regard to outcome in
      gastric cancer patients.
AB  - AIM: In order to clarify the anti-cancer effects of tumor necrosis factor-alpha
      (TNFalpha), we examined the relationship between the preoperative evaluations of
      TNFalpha and the granulocyte/lymphocyte ratio (G/L ratio) in relation to outcome
      in gastric cancer patients. MATERIALS AND METHODS: Peripheral blood samples were
      taken within 1 week before curative gastrectomy for measurement of TNFalpha and
      the G/L ratio. Five-year survival was determined in 71 operative gastric cancer
      cases. RESULTS: The 5-year survival of the high TNFalpha group (> or =8,000 pg/ml
      ) was 64.1%, 29.0% for the low TNFalpha group (<8,000 pg/ml) and 13.3 and 73.1%
      for those of the high (> or =4.0) and low (<4.0) G/L ratio groups, respectively.
      The comparisons of these 5-year survival rates showed statistically significant
      differences. Moreover, there was a negative linear correlation between TNFalpha
      and the G/L ratio regarding outcome. CONCLUSIONS: Preoperative evaluations with
      TNFalpha and the G/L ratio may be important prognostic indicators, and their
      correlation may be a good indicator of the degree of effectiveness in activating
      anti-cancer immunity in gastric cancer patients.

PMID- 20689296
TI  - Thickness of subcutaneous fat as a strong risk factor for wound infections in
      elective colorectal surgery: impact of prediction using preoperative CT.
AB  - BACKGROUND/AIMS: In this study, we have attempted to identify and assess factors
      that would be most predictive of postoperative incisional surgical site infection
      (SSI) in colorectal surgery, including representative markers for nutrition or
      obesity. METHODS: 152 patients who underwent elective colorectal resection were
      identified for inclusion in this study. The outcome of interest was incisional
      SSI. Variables thought to be predictive of incisional SSI, including body mass
      index (BMI) and the thickness of subcutaneous fat (TSF), were assessed by
      univariate and multivariate analysis. TSF was evaluated preoperatively using
      computed tomography (CT). RESULTS: The study's overall incidence of incisional
      SSI following a colorectal operation was 29 (19.1%). TSF was independently
      associated with incisional SSI. While BMI was significantly associated with
      incisional SSI on univariate analysis, this variable lost its significance on
      multivariate analysis that included TSF. Other nutritional markers were not
      significantly associated with the risk of incisional SSI. CONCLUSIONS: Our
      results suggest that the risk of incisional SSI increases with obesity, and that
      the most useful predictor of incisional SSI is TSF, as evaluated by preoperative
      CT. These findings indicate that CT is useful for the evaluation of TSF and the
      prediction of the risk of incisional SSI.

PMID- 20689297
TI  - Is total splenectomy unavoidable in the treatment of splenic benign cyst?

PMID- 20689298
TI  - Phytobezoar of the stomach - laparoscopic approach.

PMID- 20689299
TI  - Phytobezoar: impact of differential diagnosis and difficulties in technical
      diagnostics. Comment on: Park JW, Chae HD: phytobezoar of the stomach. Dig Surg
      2009;26:451-452.

PMID- 20689300
TI  - General surgery among long-term residents with and without active epilepsy at the
      Kork Epilepsy Centre - a prospective comparative one-year survey.
AB  - BACKGROUND/AIMS: We prospectively assessed the frequency, type, severity and
      cause of treatment among the long-term residents of the Kork Epilepsy Centre in
      the year 2005. METHODS: All long-term residents were exclusively referred to the
      general surgeon practicing on the campus. Patients were divided into 2 groups
      comprising 285 patients with active epilepsy and 53 controls who either never had
      epileptic seizures or have remained seizure free for at least 4 years. RESULTS:
      The 1-year incidence of injuries was 54.2% among the active epilepsy group and
      36.8% among controls (p = 0.0275). Several admissions due to differing reasons
      occurred in 16.8% of people with active epilepsy and in 7.5% of the controls (not
      significant). More than 2 admissions due to various reasons only occurred in
      patients with active epilepsy (range 3-9). Of all injuries, 41.3% were directly
      related to seizures. Among patients with active epilepsy, the 3 most frequent
      injuries were lacerations, bruises and fractures (29.6, 17.0 and 11.7%,
      respectively). CONCLUSION: According to this prospective study, active epilepsy
      turned out to be a significant risk factor for injuries under homogenous patient
      and observer conditions.

PMID- 20689301
TI  - Dual arterial cannulation for aortic surgical procedures in adult sheep.
AB  - BACKGROUND/AIMS: Preclinical site-specific placement of valvular prostheses is
      highly recommended to fully appreciate hemodynamics. An ovine model is commonly
      used for preclinical prosthetic mitral valve evaluation; however, the ideal
      animal model for prosthetic aortic valve evaluation has yet to be determined.
      Past studies have utilized adult sheep for prosthetic aortic valve replacement;
      however, an anatomically short length of the ascending aorta can present a
      surgical challenge during implantation. Due to this anatomically short length of
      the ascending aorta, we designed an arterial cannulation technique for
      cardiopulmonary bypass (CPB) to provide a more ideal operative setting. METHODS:
      Dual arterial cannulation for CPB was used in adult Polypay sheep (n = 15)
      subjected to an aortic root/valve surgical procedure. RESULTS: The arterial
      cannulation technique described in this paper was successful in performing aortic
      root/valve surgical procedures in adult sheep. All animals survived the operative
      procedure without complications. Postoperatively, all animals were alert,
      neurologically intact and assumed normal daily functions following extubation,
      which continued throughout their survival. CONCLUSIONS: The use of this arterial
      cannulation technique was safe, provided better visualization of the aortic
      root/valve area, less difficulty in performing the aortic root/valve surgical
      procedure, and less observed tissue tension while closing the aortotomy.

PMID- 20689302
TI  - GSH attenuates organ injury and improves function after transplantation of fatty
      livers.
AB  - Ischemia-reperfusion injury (IRI) is increased after transplantation of steatotic
      livers. Since those livers are increasingly used for transplantation, protective
      strategies must be developed. Reactive oxygen species (ROS) play a key role in
      hepatic IRI. In lean organs, glutathione (GSH) is an efficient scavenger of ROS,
      diminishing IRI. The aim of this study was to evaluate whether GSH also protects
      steatotic allografts from IRI following transplantation. Fatty or lean livers
      were explanted from 10-week-old obese or lean Zucker rats and preserved (obese 4
      h, lean 24 h) in hypothermic University of Wisconsin solution. Arterialized liver
      transplantation was then performed in lean syngeneic Zucker rats. Recipients of
      fatty livers were treated with GSH (200 MUmol/h/kg) or saline during reperfusion
      (2 h, n = 5). Parameters of hepatocellular damage and bile flow were measured.
      Transplantation of steatotic livers enhanced early reperfusion injury compared to
      lean organs as measured by increased aspartate aminotransferase, alanine
      aminotransferase, and lactate dehydrogenase plasma levels. Bile flow was also
      reduced in steatotic grafts. Intravenous administration of GSH effectively
      decreased liver damage in fatty allografts and resulted in improved bile flow.
      Intravenous application of GSH effectively reduces early IRI in steatotic
      allografts and improves recovery of these marginal donor organs following
      transplantation.

PMID- 20689303
TI  - Oral and vocal fold diadochokinesis in children.
AB  - AIM: To establish reference values concerning the results of oral and vocal fold
      diadochokinesis (DDK) assessment, as well as to analyze the differences among
      gender and age. METHODS: One hundred and fifty Brazilian-Portuguese-speaking
      children from 8 to 10 years old were assessed. The DDK was assessed through the
      repetition of 'pa', 'ta', 'ka', 'pataka', 'a' and 'i'. RESULTS: As age increased
      there was a rise in the average DDK rate, a rise in the coefficient of variation
      of period for syllable 'ka' and a rise in the coefficient of variation of the
      peak intensity for the syllable 'ta'. The number of utterances per second of 'ta'
      was higher for girls than for boys. In trisyllables, 8-year-old girls presented a
      lower number of utterances than the other subgroups. As age increased, there was
      a rise in the average DDK rate of the vowel 'i' for girls; there was also a
      smaller standard deviation and perturbations of the period for this same vowel.
      CONCLUSION: Oral and vocal fold DDK reference values were established and
      differences as to gender and age were observed.

PMID- 20689304
TI  - Adaptation and validation of the Italian Pediatric Voice Handicap Index.
AB  - OBJECTIVE: To evaluate the internal consistency, reliability and clinical
      validity of the Italian version of the Pediatric Voice Handicap Index (pVHI).
      PATIENTS AND METHODS: The parents of 30 children with dysphonia and 43
      asymptomatic children were included in the study. Each parent was asked to
      complete the Italian pVHI autonomously. The voice of each child was assessed
      perceptually through the GRB parameters of the GRBAS scale. Internal consistency
      was analyzed through Cronbach's alpha coefficient. For test-retest reliability
      analysis, the Italian pVHI was filled twice, with a 2-week interval, and the
      scores obtained were compared through the Pearson correlation test. Clinical
      validity was assessed comparing the scores obtained in the pathological and the
      control group using the Mann-Whitney test. Finally, the correlation between pVHI
      and the perceptual parameters was assessed. RESULTS: All of the parents filled in
      the entire questionnaire autonomously. An optimal internal consistency was found
      (alpha = 0.95); the test-retest reliability in the parents of both groups of
      children was high (r > 0.88). The control group scored significantly lower than
      the pathological group (p = 0.0001). The pVHI scores positively correlated with
      perceptual assessment of voice disorders. CONCLUSION: The Italian pVHI is easily
      administered, highly reproducible, and exhibits excellent clinical validity.

PMID- 20689305
TI  - Speech pathology interventions in patients with neuromuscular diseases: a
      systematic review.
AB  - PURPOSE: A systematic review was conducted to summarize and evaluate the
      literature on the effectiveness of speech pathology interventions in adults with
      neuromuscular diseases. METHOD: Databases searched included the Cochrane Database
      of Systematic Reviews, the Cochrane Central Register of Controlled Trials,
      MEDLINE, CINAHL, EMBASE, PsycINFO and PubMed. A total of 1,772 articles were
      independently screened on title and abstract by 2 reviewers. RESULTS: No
      randomized controlled trials or clinical controlled trials were found. Four other
      designs were included. Only one study on oculopharyngeal muscle dystrophy (OPMD)
      appeared to have sufficient methodological quality. There is evidence indicating
      that correction of head position in patients with OPMD improves swallowing
      efficiency (level III evidence). CONCLUSION: Despite 1,772 studies, there is only
      evidence of level III regarding the effectiveness of speech pathology
      interventions in patients with OPMD. Recommendations for future research are
      given.

PMID- 20689306
TI  - The impact of vocal intensity and pitch modulation on nasalance scores: a pilot
      study.
AB  - OBJECTIVE: The purpose of this study was to examine the impact of pitch and
      intensity modulation on nasalance scores. METHODS: A single-group pretest
      posttest design was used in which subjects produced reading passages at different
      pitch and intensity levels. The Nasometer was used for the registration of
      nasalance scores in subjects with and without cleft palate. RESULTS: An increase
      in intensity in the non-cleft group resulted in a small but significant decrease
      in nasalance. Lowering the pitch level resulted in a small but significant
      decrease in nasalance scores for both the non-cleft and cleft palate subjects.
      CONCLUSIONS: The nasalance changes after vocal modulations during connected
      speech are reliable and not biased but the impact of these vocal changes on
      speech intelligibility and daily communication and the usefulness of these vocal
      modulations as part of a behavioral management program is not yet proven.

PMID- 20689307
TI  - Health-related quality of life of children with specific language impairment aged
      8-11.
AB  - OBJECTIVE: To evaluate, in a clinical sample of children with a diagnosis of
      specific language impairment (SLI), the health-related quality of life (HRQoL).
      SUBJECTS AND METHODS: Fifty-five children, aged 8-11 years, filled out a generic
      HRQoL questionnaire, 17D, and another questionnaire about school and
      rehabilitation. The HRQoL comparison group was a sample of 244 typically
      developing schoolchildren. RESULTS: Response rate was 86%. Of the respondents,
      80% were male. The total 17D score of the subjects did not differ from that of
      controls. The 17D profiles of the groups differed on several dimensions, but
      significant differences emerged only on the dimensions concerning speech, where
      the study group was worse off, and sleep, where the controls reported more
      problems. Respondents with low verbal IQ reported more distress. The vast
      majority of respondents were in special education or received extra educational
      support and one-third were still having speech therapy. CONCLUSION: In this
      clinical sample, despite the persisting need for extra support, the overall well
      being of children with SLI was at age level. Still, some differences existed, and
      HRQoL measurement may prove a good tool for professionals to find those children
      with SLI at risk for diminished well-being and for later problems.

PMID- 20689308
TI  - Variability in execution of the chin-down maneuver by healthy adults.
AB  - OBJECTIVE: The chin-down maneuver is commonly used in dysphagia management to
      facilitate greater airway protection. However, the literature suggests that
      variation in maneuver execution may threaten the effectiveness of the
      intervention. Our goal was to study variation in chin-down maneuver execution
      given a uniform instruction. METHODS: Sagittal view digital video recordings were
      acquired from 408 healthy adults who performed sequences of reiterated water
      swallows in head-neutral and chin-down positions. Head angle measurements were
      extracted from the recordings, using markers on goggles worn by 176 participants.
      RESULTS: We observed considerable variation in head angle in the head-neutral
      swallowing task, with a trend to greater flexion in participants over the age of
      65. Male participants showed greater variation in head angle than females. Head
      flexion during the chin-down swallowing tasks averaged 19 degrees , in the range
      reported to yield clinical benefit in radiographic studies. CONCLUSION: We
      conclude that a clear, uniform instruction is adequate to facilitate execution of
      the chin-down maneuver to a degree that is likely to be of clinical benefit. The
      variation in head angle observed in this study warrants further research,
      particularly regarding the relationship between anatomical cervical spine
      curvature and head angle influence on swallowing.

PMID- 20689309
TI  - Fast and robust association tests for untyped SNPs in case-control studies.
AB  - Genome-wide association studies (GWASs) aim to genotype enough single nucleotide
      polymorphisms (SNPs) to effectively capture common genetic variants across the
      genome. Even though the number of SNPs genotyped in such studies can exceed a
      million, there is still interest in testing association with SNPs that were not
      genotyped in the study sample. Analyses of such untyped SNPs can assist in signal
      localization, permit cross-platform integration of samples from separate studies,
      and can improve power - especially for rarer SNPs. External information on a
      larger collection of SNPs from an appropriate reference panel, comprising both
      SNPs typed in the sample and the untyped SNPs we wish to test for association, is
      necessary for an untyped variant analysis to proceed. Linkage disequilibrium
      patterns observed in the reference panel are then used to infer the likely
      genotype at the untyped SNPs in the study sample. We propose here a novel
      statistical approach for testing untyped SNPs in case-control GWAS, based on an
      efficient score function derived from a prospective likelihood, that
      automatically accounts for the variability in the process of estimating the
      untyped variant. Computationally efficient methods of phasing can be used without
      affecting the validity of the test, and simple measures of haplotype sharing can
      be used to infer genotypes at the untyped SNPs, making our approach
      computationally much faster than existing approaches for untyped analysis. At the
      same time, we show, using simulated data, that our approach often has performance
      nearly equivalent to hidden Markov methods of untyped analysis. The software
      package 'untyped' is available to implement our approach.

PMID- 20689310
TI  - Expression of E1E2 on hepatitis C RNA-containing particles released from primary
      cultured human hepatocytes derived from infected cirrhotic livers.
AB  - OBJECTIVE: To determine whether liver-derived hepatitis C RNA-containing
      particles express the E1E2 discontinuous antigenic determinant defined by unique
      monoclonal antibody (mAb) D32.10 which recognizes three highly conserved segments
      in E1 (aa297-306) and E2 (aa480-494 and aa613-621) envelope glycoproteins.
      METHODS: Human hepatocytes were isolated from HCV-infected cirrhotic explanted
      livers. The liver-derived hepatitis C virus (HCV) particles released from three
      distinct cultures (genotypes 1b and 2b) were characterized. HCV RNA+ was
      quantified by real-time RT-PCR. The E1E2 antigenic activity was assessed by
      indirect ELISA and immunoblotting using D32.10. The density distributions of HCV
      RNA and E1E2 antigen were determined by isopycnic sucrose density gradients. HCV
      E1E2, E2 and core antigens were detected in the cells by immunochemical staining.
      RESULTS: Liver-derived HCV particles contained HCV RNA (106-107 copies/mg of
      protein) and core proteins and expressed the E1E2/D32.10 epitope. HCV RNA and
      E1E2 cosedimented between 1.15 and 1.25 g/ml in sucrose gradients. Moreover, the
      mAb D32.10 detected E1E2 by immunostaining in HCV-infected hepatocytes in
      parallel with E2 and core antigens. CONCLUSION: Our results provide evidence that
      the mAb D32.10 recognizes E1E2 envelope complexes expressed in the cell cytoplasm
      and on the surface of HCV RNA-containing particles released from short-term
      cultures of in vivo infected hepatocytes.

PMID- 20689311
TI  - Seroprevalence and genotype of hepatitis C virus among immigrant workers from
      Cambodia and Myanmar in Thailand.
AB  - OBJECTIVE: There is a large number of immigrant workers from Cambodia and Myanmar
      in Thailand. The aim of our study was to determine seroprevalence and genotypes
      of hepatitis C virus (HCV) in this group. METHODS: Immigrants aged between 15 and
      60 years (1,431 Cambodians and 1,594 Myanmarese) were recruited into this study.
      Each sample was screened for anti-HCV by ELISA. RNA was extracted from
      seropositive samples and RT-PCR was performed in order to amplify the HCV core
      region. Each sample was subsequently sequenced, and the genotype was determined
      by phylogenetic analysis. RESULTS: The prevalence of HCV infection in immigrant
      workers from Cambodia and Myanmar was 33 (2.3%) and 27 (1.69%) samples,
      respectively. Of the anti-HCV-positive individuals, 25 (75.8%) from Cambodia and
      15 (55.6%) from Myanmar harbored viral RNA. Phylogenetic analysis showed that the
      predominant HCV genotypes in this group were 1a, 1b, 3a, 3b and 6 (6e, 6f, 6m, 6p
      and 6r). Most HCV isolates can be found in Thailand, though some subtypes of HCV
      6 are uncommon. CONCLUSIONS: This study shows the HCV seroprevalence and
      genotypes among immigrant Cambodians and Myanmarese which may reflect the
      prevalence in each country and closely relate to the prevalence in the guest
      country.

PMID- 20689312
TI  - In vitro Epstein-Barr virus infection model of rabbit lymphocytes from peripheral
      blood or spleen.
AB  - Most humans become lifelong carriers of Epstein-Barr virus (EBV) by adulthood.
      Primary EBV infection in adolescents causes infectious mononucleosis. EBV
      infection is associated with various diseases, neoplasms and hematological
      disorders. Recently, we reported that EBV can infect rabbits by intravenous,
      intranasal and/or peroral inoculation, which caused primary EBV infection in
      rabbits with heterogeneous host reactions. Some rabbits showed chronic and
      lifelong EBV infection with hemophagocytosis. In this study, to reveal detailed
      mechanisms in rabbit EBV infection, an in vitro investigation was performed. We
      elucidated that: (1) EBV can infect rabbit peripheral blood mononuclear cells and
      splenic lymphocytes in vitro, because EBV gene expressions were confirmed. (2) It
      is highly likely that the B cell is the main target cell of rabbit EBV infection
      and is immortalized similar to humans. (3) CD8+ T cells increased in the rabbit
      in vivo model after EBV inoculation, whereas an increase of B cells occurred
      after their transient decrease. These data suggest that EBV-infected B cells were
      proliferated, while CD8+ T cells increased to recognize and kill them. This
      system may explain the paths of rabbit EBV infection and host reaction,
      simulating human EBV infection. In vitro studies will be helpful to reveal the
      pathogenesis of rabbit EBV infection and EBV-associated diseases.

PMID- 20689313
TI  - Human herpesvirus 7 in allogeneic hemopoietic stem cell transplant recipients in
      the central clinical hospital in Warsaw: a three-year survey.
AB  - OBJECTIVES: Human herpesvirus 7 (HHV-7) is spread worldwide and has been
      described as a potential pathogen in immunosuppressed patients. Different
      clinical manifestations have been described including fever and skin rash; HHV-7
      may also be a possible cofactor for cytomegalovirus disease in transplant
      recipients. MATERIALS AND METHODS: A retrospective review of a group of 58 adult
      recipients of allogeneic hemopoietic stem cell transplantation was made. Serum
      samples taken in the range of 0-180 days after transplant were examined for
      presence of specific HHV-7 sequences using the quantitative real-time PCR method.
      RESULTS: HHV-7 DNA was detected in plasma samples in 26 (45%) of the 58
      recipients between day 20 and day 65 of transplantation. All of them developed
      fever of unknown origin; also HHV-5 DNA was detected in plasma samples collected
      from 11 HHV-7-positive patients. None of the described individuals died during
      detectable HHV-7 or HHV-5 viremia periods. CONCLUSIONS: There is a high frequency
      of detectable HHV-7 viral load in allogeneic stem cell transplant recipients in
      Poland. Limited availability and sensitivity of serological methods along with
      the necessity of rapid introduction of antiviral treatment has forced the
      development of molecular diagnostics. Furthermore, establishment of appropriate
      procedures for monitoring active HHV-7 infection is important to clarify the
      virus infection in transplant recipients.

PMID- 20689314
TI  - Extended phylogeny of the equine arteritis virus sequences including South
      American sequences.
AB  - OBJECTIVE: To perform genetic analysis of the ORF5 of equine arteritis virus
      (EAV) may provide new insights into the genetic evolution and origin of the
      Argentinean EAV sequences. METHODS: A total of 76 sequences were analyzed by
      neighbor joining (NJ), maximum parsimony and maximum likelihood algorithms. The
      analysis of the selective pressures was performed using the Tajima's test.
      RESULTS: The trees showed similar topologies. Two clades were identified: the
      first clade was formed by strains isolated mainly from a donkey, whereas the
      second clade presented four large groups from different geographic regions
      exclusively from Equus caballus. In this clade, we identified a group formed by
      South African and another one by South American and European sequences. In the
      latter, the monophyletic group was formed by seven Argentinean sequences. In the
      NJ tree, we identified a group formed by six Argentinean sequences. The Tajima's
      test showed a D value of 1.73663, indicating that the sequences analyzed follow a
      neutral evolution model. CONCLUSION: We concluded that the Argentinean sequences
      have a paraphyletic origin and that the fixation of point mutation might follow
      the neutral model evolution; however, we identified purifying pressures that may
      be involved in the differentiation of the EAV sequences.

PMID- 20689315
TI  - Identification of structural proteins of Bombyx mori parvo-like virus (China
      Zhenjiang isolate).
AB  - OBJECTIVE: Bombyx mori parvo-like virus is a type of virus containing two single
      stranded linear DNA molecules (VD1, VD2). In the present work, the structural
      proteins of B. mori parvo-like virus (China Zhenjiang isolate) (BmDNV-Z) were
      identified. METHODS: The virions were purified by cesium chloride density
      gradient centrifugation from the feces of B. mori larvae infected with BmDNV-Z
      and analyzed by SDS-PAGE, Western blotting and MALDI-TOF/mass spectometry.
      RESULTS: There were seven polypeptides of the virions, named P1 to P7, which
      reacted with the anti-virion serum. In addition, two polypeptides, P5 and P6,
      were recognized by the antibody against a viral protein encoded by VD1-ORF3.
      CONCLUSION: The results showed that the viral polypeptides were mainly composed
      of 7 proteins named P1 to P7. Western blotting with anti-virion serum indicated
      that structural proteins P5, P6 and P7 had molecular weights of around 50, 55 and
      130 kDa, respectively. They were the major immunogens of the virion. Among them,
      P5 and P6 were coded by VD1-ORF3 and P7 was encoded by VD2-ORF1. Taken together,
      three viral structural proteins encoded by VD1-ORF3 and VD2-ORF1 were identified
      in BmDNV-Z for the first time.

PMID- 20689316
TI  - Structure of vibriophage D10 tail sheath revealed by electron microscopy and
      computational image processing.
AB  - Vibriophage D10, a member of the Vibrio cholerae O-1El-Tor phage typing scheme,
      is used to detect the spread of the cholera epidemic and belongs to the
      Myoviridae family. The outer sheath of the tail of vibriophage is highly
      contractile in nature. We have used electron microscopy and computational image
      processing techniques to determine the structure of this contractile tail sheath.
      The three-dimensional density map of the tail sheath reveals the presence of ~35
      A long and ~25 A wide protrusions, extending out of the tail structure. The
      electron micrographs revealed that the tail sheaths of a considerable number of
      D10 phage particles undergo axial compression up to 51% at almost neutral pH
      (7.2) and at room temperature (20 degrees ). We find that the genome of the phage
      particles is ejected out when the tail sheath of the phage particles are
      deliberately made to contract by subjecting them to a surrounding environment of
      pH 10.5. We infer that the contraction of the tail sheath is responsible for the
      loss of the phage genome even at neutral pH and room temperature. This may be a
      plausible reason for the unusual behavior of rapid decline of the phage within a
      span of 48-72 h of its preparation.

PMID- 20689317
TI  - Rotavirus genotypes in Costa Rica, Nicaragua, Honduras and the Dominican
      Republic.
AB  - In this study, 574 stool samples from children with gastroenteritis were obtained
      from different hospitals in Costa Rica, Honduras, Nicaragua and the Dominican
      Republic during 2005-2006. Diarrhea stool samples were analyzed for rotavirus
      (RV) by ELISA and typed by the RT-PCR-based method. Unusual strains were
      detected: G1P6, G2P8, G3P6, G9P4, and mixed infections. Recent studies have
      indicated that unusual human RV strains are emerging as global strains, which has
      important implications for effective vaccine development. In this context, the
      next generation of RV vaccines will need to provide adequate protection against
      diseases caused not only by mixed infections, but also by unusual G/P
      combinations.

PMID- 20689318
TI  - Biosimilars and regulatory authorities.
AB  - The patent expirations for many biotechnological medicines have prompted the
      development of copies of biological medicinal products. Unlike generics,
      biosimilars are similar but not identical to their reference product, because
      their chemical characteristics are directly related to the manufacturing process
      which cannot be precisely duplicated. The regulatory policy for biosimilars is
      complex and in Europe it is regulated mainly by guidelines issued by the European
      Medicines Agency (EMEA); additional product-class specific guidelines have been
      developed as in the case of recombinant human erythropoietin (rHuEPO). In 2008,
      the experience gained with this drug has prompted the development of a new
      guideline, currently in draft. In this review we critically discuss aspects
      related to EMEA guidelines, particularly focusing on rHuEPO.

PMID- 20689319
TI  - Oral cyclophosphamide is on the verge of extinction as therapy for severe
      autoimmune diseases (especially lupus): should nephrologists care?
AB  - Some day we will have powerful targeted therapies for autoimmune diseases.
      Remission will be induced efficiently. Side effects will be mere ripples.
      Unfortunately, that day is not imminent. Current therapies are powerful but with
      unintended targets and side effects that can be equivalent to a sea change. For
      SLE, the current competition to select the 'gold standard' immunosuppressant has
      come down to two regimens: intravenous cyclophosphamide (IVCY, standard NIH
      protocol or its variations) versus oral mycophenolate (MMF). Until recently, IVCY
      reigned as the gold standard, a title it achieved through a curious journey that
      did not involve rigorous head-to-head competition. Oral cyclophosphamide (POCY)
      has not been invited to the current competition to select the gold standard
      immunosuppressant despite the substantial evidence that POCY can perform at least
      as well as IVCY or mycophenolate, and compared to IVCY, is far less expensive,
      easier for the patient, and maybe more effective in African-Americans. Here, we
      state the case for POCY as therapy for severe autoimmune diseases. We suggest
      that if POCY is allowed to compete, it will not disappoint.

PMID- 20689320
TI  - Vitamin K2 alters bone metabolism markers in hemodialysis patients with a low
      serum parathyroid hormone level.
AB  - BACKGROUND: A low level of intact parathyroid hormone (PTH) is an indicator of
      adynamic bone disease in hemodialysis patients, and is associated with a
      significant increase of all-cause mortality. Thus, effective treatment for
      adynamic bone disease is required. We previously investigated the effect of
      vitamin K2 on adynamic bone disease. In this study, we assessed the efficacy of
      oral vitamin K2 in a controlled trial. METHODS: Forty hemodialysis patients with
      low intact PTH levels (<100 pg/ml) were randomly divided into two groups, which
      were a vitamin K2 group receiving oral menatetrenone (45 mg/day) for 1 year and a
      control group without vitamin K2. Venous blood samples were collected at baseline
      and during the study for measurement of bone metabolism parameters. RESULTS:
      Thirty-three patients completed follow-up. There was a significant increase of
      the serum intact osteocalcin level after 1 month of vitamin K2 administration.
      Serum levels of intact PTH, bone alkaline phosphatase, and cross-linked N
      terminal telopeptide of type I collagen increased significantly after 12 months
      in the vitamin K2 group. The serum osteoprotegerin level was decreased after 12
      months in the vitamin K2 group, but the change was not significant. CONCLUSION:
      Vitamin K2 therapy improves bone remodeling in hemodialysis patients with a low
      intact PTH level.

PMID- 20689321
TI  - Clinical impact of renal biopsy on outcomes in elderly patients with nephrotic
      syndrome.
AB  - BACKGROUND/AIMS: The number of elderly patients with nephrotic syndrome (NS) is
      increasing. This study aimed to assess the implications of renal biopsy on the
      outcomes in elderly patients with NS. METHODS: Ninety-nine patients diagnosed
      with NS who were over 60 years of age were reviewed. Secondary NS related to
      diabetes was excluded. Histopathological diagnosis, comparison of outcomes
      between the biopsied group (n = 64) and the nonbiopsied group (n = 35) and
      factors affecting renal survival were evaluated. RESULTS: The biopsied group was
      significantly younger and had better renal function than the nonbiopsied group.
      More patients in the biopsied group than in the nonbiopsied group received
      immunosuppressive treatment (76.6 vs. 42.9%, p < 0.005), and achieved complete
      remission (45.3 vs. 26.5%, p = 0.013). The complication rates and renal survival
      rates were not different between the two groups, but the patient survival rates
      were significantly higher in the biopsied group (p < 0.005). Predictors for renal
      survival were renal function at diagnosis and response to treatment. CONCLUSION:
      Renal biopsy is essential for a correct diagnosis and directed therapeutic
      approach in elderly patients with NS and may improve the clinical outcomes of
      these patients.

PMID- 20689322
TI  - Factors associated with recovery of renal function in patients with multiple
      myeloma who were treated with hemodialysis.
AB  - BACKGROUND: The presence of renal failure in patients with multiple myeloma (MM)
      has been considered an ominous prognostic factor associated with a significantly
      decreased life expectancy. The prognostic factors have seldom been analyzed to
      predict discontinuation of hemodialysis (HD) therapy in MM patients with renal
      failure after HD initiation. It is clinically very important to predict whether
      HD can be discontinued after introducing HD in such patients. METHODS: All
      medical and HD records were reviewed in MM patients who underwent HD in the
      National Center for Global Health and Medicine Hospital between January 1995 and
      May 2009. Thirty-two patients with MM had undergone HD. The clinical features and
      the factors that might be associated with recovery of renal function leading to
      discontinuation of HD in MM patients with severe renal failure were examined.
      RESULTS: The factors associated with recovery of renal function and
      discontinuation of HD were: low International Staging System (ISS) score (p =
      0.0034); high response to chemotherapy (p = 0.036); low serum Ca (p = 0.006); low
      Cr (p = 0.019), and low serum beta2-microglobulin (sbeta2M) (p = 0.002). On
      multivariate analysis, low serum Ca and sbeta2M were significantly associated
      with HD discontinuation. Moreover, discontinuing HD was the significant factor
      associated with improved overall survival in MM patients who required HD at least
      once. CONCLUSION: sbeta2M and Ca were the laboratory parameters that were
      significant, independent prognostic factors for predicting the probability of
      recovery from severe renal failure and discontinuation of HD in MM patients who
      needed HD at least once.

PMID- 20689323
TI  - Factors associated with nonadherence to medication in kidney transplant
      recipients.
AB  - Nonadherence in kidney transplant recipients was evaluated in this report using a
      questionnaire with five binary questions and one question on a continuous scale.
      Study participants at the University of Utah Transplant Program (n = 199) were
      43.0 +/- 14.2 years old; 67% were males, and 81% were White. Two questions that
      produced heterogeneous outcome were analyzed: 'Do you ever forget to take your
      medication?' (79% no, 21% yes) and 'Have you ever taken your medications late?'
      (67% no, 33% yes). Responses to these questions correlated (chi2 65.2, p < 0.001;
      correlation coefficient 0.57, p < 0.001). We performed a logistic regression
      analysis to identify factors associated with the combined outcome of
      forgetting/not taking medications altogether or taking medications off schedule.
      Higher comorbidity index [odds ratio (OR) 2.19, p < 0.001], living (compared to
      deceased) donor (OR 2.81, p = 0.005) and full-time employment were associated
      with forgetting medications or taking them late (OR 3.12, p = 0.01). Recipient
      age tended to be associated with lower risk of nonadherence, but did not reach
      statistical significance (OR 0.98 per year of age, p = 0.13). Education level,
      smoking status, recipient race, dialysis modality, number of medications and the
      time since first kidney transplantation were not associated with the outcome. In
      conclusion, renal transplant recipients with greater comorbidity, receiving
      kidney from a living donor and with full-time employment reported lower levels of
      medication adherence.

PMID- 20689324
TI  - Estimation of the age-dependent decline of glomerular filtration rate from
      formulas based on creatinine and cystatin C in the general elderly population.
AB  - BACKGROUND/AIMS: To evaluate the performance of estimation formulas for
      glomerular filtration rate (GFR) based on creatinine and cystatin C in elderly.
      METHODS: This study includes 2,931 men and women comprising nine age cohorts (60
      93 years) from a longitudinal population-based project in Sweden. The
      participants were divided into four age groups. GFR was estimated from four
      formulas: the Modification of Diet in Renal Disease (MDRD), CKD-EPI and Cockroft
      Gault (CG) based on creatinine and one based on cystatin C (eGFR-CysC). CG was
      also adjusted for body surface area (BSA) to CG/BSA. RESULTS: CG, CG/BSA and eGFR
      CysC yielded significantly lower GFR values compared to MDRD and CKD-EPI in the
      oldest persons (>80 years). A low GFR (<30 ml/min/1.73 m2) was demonstrated with
      MDRD in 3.3% (80-89 years) and in 6.3% (>90 years). With CG/BSA it was 8.0% (80
      89 years) and 27.2% (>90 years), and with eGFR-CysC it was 12.1% (80-89 years)
      and 27% (>90 years), respectively. The individual formulas showed different eGFR
      in the four age cohorts and also different slopes by increasing age. CG/BSA and
      eGFR-CysC both show steeper declines than MDRD and CKD-EPI. CONCLUSION: Age
      associated decline of renal function is common in elderly and increases immensely
      after the age of 80 years. More than 25% of the oldest demonstrate eGFR <30
      ml/min/1.73 m2. CG and eGFR-CysC yielded the highest prevalence of decline and
      MDRD the lowest.

PMID- 20689325
TI  - C-reactive protein is a predictor for developing proteinuria in a screened
      cohort.
AB  - BACKGROUND: The relationship between C-reactive protein (CRP) and proteinuria is
      not known. METHODS: We examined 20,077 screenees (men: 52.4%) of the Okinawa
      General Health Maintenance Association (OGHMA) registry who were examined between
      2004 and 2006. Cross-sectional and longitudinal relationships between CRP and
      dipstick proteinuria were examined. The OGHMA central laboratory measured
      creatinine and CRP levels using an autoanalyzer (normal: <0.30 mg/dl). The
      glomerular filtration rate was estimated using the Japanese formula. RESULTS: The
      prevalence of dipstick-positive proteinuria increased from 5.2% in screenees with
      a low CRP level of <0.10 mg/dl to 12.3% in those with high CRP levels (0.30-0.90
      mg/dl). The CRP values did not affect the mean (SD) estimated glomerular
      filtration rate: 76.9 (13.7) with low CRP and 76.4 (15.1) with high CRP levels.
      We examined the relationship between baseline CRP and the development of
      proteinuria among subjects screened in 2004. Of 8,315 subjects without
      proteinuria examined again by 2006, 370 (4.4%) had developed proteinuria. The
      odds ratio (95% CI) for high CRP levels (0.30-0.90 mg/dl; reference CRP: <0.10
      mg/dl) was 1.433 (1.013-2.028; p = 0.0422) after adjusting for multivariate
      variables, suggesting that CRP is closely associated with the prevalence and
      incidence of proteinuria. CONCLUSION: A prospective study on the development of
      proteinuria among those with high CRP levels is warranted. Screenees with high
      CRP levels may need to be followed up carefully despite the absence of
      traditional risk factors for proteinuria.

PMID- 20689326
TI  - Increased ACE and decreased ACE2 expression in kidneys from patients with IgA
      nephropathy.
AB  - BACKGROUND: Angiotensin-converting enzyme (ACE)2 forms angiotensin-1-7 which may
      protect kidney in a counterregulatory manner to angiotensin II. Recent studies
      revealed increased ACE and decreased ACE2 expression in kidneys of patients with
      diabetic nephropathy. However, these changes may not be specific for diabetic
      nephropathy. We studied ACE and ACE2 expression in patients with IgA nephropathy.
      METHODS: Renal ACE and ACE2 expression was assessed by immunohistochemistry and
      in situ hybridization in 30 patients with IgA nephropathy and 21 healthy
      controls. Correlation between ACE and ACE2 expression and levels of various
      biochemical parameters was also assessed. Gene expression was also assessed in
      minimal change nephrotic syndrome (MCNS) and membranous nephropathy (MN) as
      disease controls. RESULTS: Reduced ACE2 expression (p < 0.01) and increased ACE
      expression in glomeruli (p < 0.001), and reduced ACE2 expression in
      tubulointerstitium (p < 0.001) were observed in patients with IgA nephropathy
      compared to healthy controls, although the changes in ACE2 mRNA were not
      statistically significant. Reduced renal ACE2 expression was also found in MN but
      not in MCNS. Correlation between renal ACE and ACE2 expression and proteinuria
      was not observed in IgA nephropathy. CONCLUSION: IgA nephropathy is associated
      with increased ACE and decreased ACE2 expression in kidneys, as in diabetic
      nephropathy.

PMID- 20689327
TI  - Left ventricular mass index is an independent determinant of diastolic
      dysfunction in patients on chronic hemodialysis: a tissue Doppler imaging study.
AB  - BACKGROUND: Diastolic heart failure is the most common clinical form of heart
      failure. Tissue Doppler imaging (TDI) is often used to quantitate left
      ventricular (LV) diastolic function. The purpose of this study was to identify
      the determinant(s) of diastolic dysfunction in patients with end-stage renal
      disease on hemodialysis (HD), using the TDI method. METHODS: The study subjects
      were 53 patients with end-stage renal disease and preserved LV systolic function
      on maintenance HD. LV function was assessed by conventional echocardiography. The
      ratio of early trans-mitral flow velocity to early mitral annular velocity (E/e')
      was measured by TDI. Patients were stratified into two groups based on E/e' value
      (<=15 and >15 groups). Arterial stiffness was evaluated by pulse wave velocity
      and cardio-ankle vascular index. RESULTS: Patients of the E/e' >15 group were
      older (p = 0.025). There were no significant differences in blood pressure,
      ejection fraction, E/A, deceleration time, and pulse wave velocity between the
      E/e' >15 and E/e' <=15 groups. However, there were significant differences in LV
      mass index (LVMI; p < 0.001) and cardio-ankle vascular index (p = 0.048) between
      the two groups. Multiple regression analysis identified that LVMI was an
      independent determinant of E/e' (p = 0.003). CONCLUSIONS: Our findings suggest
      that LVMI is an independent determinant of LV diastolic dysfunction in patients
      on HD.

PMID- 20689328
TI  - Fibroblast growth factor 23 in hemodialysis patients: effects of phosphate
      binder, calcitriol and calcium concentration in the dialysate.
AB  - BACKGROUND: Fibroblast growth factor 23 (FGF23) concentrations increase early in
      chronic kidney disease (CKD), and the influence of current CKD-mineral and bone
      disorder (MBD) therapies on serum FGF23 levels is still under investigation.
      METHODS: In this post-hoc analysis of a randomized clinical trial, phosphate
      binders and calcitriol were washed out of 72 hemodialysis patients who were then
      submitted to bone biopsy, coronary tomography and biochemical measures, including
      FGF23. They were randomized to receive sevelamer or calcium acetate for 1 year
      and the prescription of calcitriol and the calcium concentration in the dialysate
      were adjusted according to serum calcium, phosphate and PTH and bone biopsy
      diagnosis. RESULTS: At baseline, bone biopsy showed that 58.3% had low-turnover
      bone disease, whereas 38.9% had high-turnover bone disease, with no significant
      differences between them with regard to FGF23. Median baseline FGF23 serum levels
      were elevated and correlated positively with serum phosphate. After 1 year, serum
      FGF23 decreased significantly. Repeated measures ANOVA analysis showed that the
      use of a 3.5-mEq/l calcium concentration in the dialysate, as well as the
      administration of calcitriol and a calcium-based phosphate binder were associated
      with higher final serum FGF23 levels. CONCLUSIONS: Taken together, our results
      confirm that the current CKD-MBD therapies have an effect on serum levels of
      FGF23. Since FGF23 is emerging as a potential treatment target, our findings
      should be taken into account in the decision on how to manage CKD-MBD therapy.

PMID- 20689329
TI  - Experimental peritoneal sclerosis models should not be based on chlorhexidine
      gluconate anymore.
AB  - BACKGROUND/AIMS: Currently available rodent models of peritoneal sclerosis are
      not based on clinically relevant factors: renal failure in combination with
      exposure to bioincompatible fluids. Our aim was to develop a chronic peritoneal
      infusion model of peritoneal sclerosis in rats with renal failure. METHODS: Male
      Wistar rats underwent a catheter implantation and a 70% nephrectomy. They were
      randomly divided into three peritoneal infusion groups: chlorhexidine
      gluconate/ethanol (CGE) + Dianeal (Baxter Healthcare, Castlebar, Ireland), CGE +
      buffer (Physioneal without glucose; Baxter, Nivelles, Belgium) and Dianeal alone.
      After 8 weeks a peritoneal permeability test was performed and omental tissue was
      obtained for morphometrics. RESULTS: The CGE + Dianeal group (n = 6) and CGE +
      buffer (n = 6) group showed high peritoneal clearances of small solutes and
      proteins, ultrafiltration failure, impaired free water transport, severe fibrosis
      and high vessel counts, but the groups did not differ significantly. The Dianeal
      group (n = 6) showed significantly lower clearances of small solutes and
      proteins, normal ultrafiltration and sodium sieving, and significantly lower
      fibrosis scores and vessel counts. CONCLUSIONS: Abnormalities seen in peritoneal
      sclerosis can be induced in a peritoneal infusion model in rats with renal
      failure. However, the addition of a bioincompatible dialysis solution had no
      contributing role, probably because the effects were overruled by those of CGE.

PMID- 20689330
TI  - Involvement of connective tissue growth factor in human and experimental
      hypertensive nephrosclerosis.
AB  - BACKGROUND/AIMS: Connective tissue growth factor (CTGF; CCN2) has been implicated
      as a marker and mediator of fibrosis in human and experimental renal disease.
      METHODS: We performed a comparative analysis of CTGF expression in hypertensive
      patients with and without nephrosclerosis, and in uninephrectomized and sham
      operated spontaneously hypertensive rats (UNX-SHR and 2K-SHR). RESULTS: Urinary
      and plasma CTGF were elevated in patients with hypertensive nephrosclerosis, and
      increased renal CTGF expression was mainly localized in podocytes. Accordingly,
      elevation of urinary, plasma, and tissue CTGF in UNX-SHR coincided and correlated
      with proteinuria, glomerulosclerosis, and tubulointerstitial fibrosis. Thirty-two
      weeks after uninephrectomy, mean glomerular CTGF mRNA expression was increased
      1.3-fold over baseline, mainly due to 1.7-fold higher expression in glomeruli
      undergoing sclerosis. In parallel, tubulointerstitial CTGF and alpha-smooth
      muscle actin were upregulated in UNX-SHR. CTGF was increased in the media of
      arcuate and interlobar arteries, while arterioles remained negative. CONCLUSIONS:
      Glomerulosclerosis, tubulointerstitial fibrosis, and arterial media hypertrophy
      lesions of hypertensive nephrosclerosis are all characterized by increased CTGF
      tissue expression, which is associated with a concomitant increase in CTGF in
      blood and urine. These findings identify CTGF as a promising biomarker for
      progression of hypertensive nephrosclerosis, and as a likely key factor in the
      pathogenesis of this disease.

PMID- 20689331
TI  - Erythropoietin protects podocytes from damage by advanced glycation end-products.
AB  - BACKGROUND: Podocyte damage and accumulation of advanced glycation end-products
      (AGEs) are implicated in the development and progression of diabetic nephropathy.
      We have previously shown that changes in podocyte pathophysiology, such as
      hypertrophy and reduced migration, are closely linked with the induction of the
      cell cycle inhibitor p27(Kip1) and a decrease in neuropilin-1 (NRP1) expression.
      We investigated whether the erythropoietin receptor activators CERA and epoetin
      beta may prevent AGE-mediated changes in podocytes. METHODS: Differentiated mouse
      podocytes in culture were challenged by AGE-modified bovine serum albumin (BSA)
      or control BSA in the presence or absence of CERA as well as epoetin-beta. Cell
      cycle analysis and determination of apoptosis markers were performed. p27(Kip1)
      and NRP1 expression was measured by RT-PCR and Western blots. RESULTS:
      Differentiated mouse podocytes in culture expressed erythropoietin receptors
      which were phosphorylated after incubation with CERA or epoetin-beta. CERA or
      epoetin-beta prevented the p27(Kip1)-dependent cell cycle arrest and cellular
      hypertrophy induced by AGE-BSA incubation. Furthermore, the p27(Kip1)-dependent
      AGE-BSA-induced decrease in cell viability and decrease in cell proliferation was
      ameliorated in the presence of CERA or epoetin-beta. Following erythropoietin
      treatment, AGE-BSA failed to further reduce NRP1 expression, resulting in
      improved podocyte migration. CONCLUSION: Treatment with the erythropoietin
      receptor activators epoetin-beta or CERA protected podocytes from AGE-BSA
      mediated damage via an effect on p27(Kip1) and NRP1 expression. Consequently,
      early treatment with erythropoietin may help to prevent diabetic nephropathy.

PMID- 20689332
TI  - Blood gases and retinopathy of prematurity: the ELGAN Study.
AB  - OBJECTIVE: This study tested the hypothesis that preterm infants who had a blood
      gas derangement on at least 2 of the first 3 postnatal days are at increased risk
      for more severe retinopathy of prematurity (ROP). METHOD: 1,042 infants born
      before 28 weeks' gestational age (GA) were included. An infant was considered to
      be exposed if his/her blood gas measure was in the highest or lowest quartile for
      GA on at least 2 of the first 3 postnatal days. RESULTS: Multivariable models
      adjusting for confounders indicate that exposure to a PCO(2) in the highest
      quartile predicts ROP (stage 3, 4 or 5: OR = 1.6, 95% CI = 1.1-2.3); zone 1: 2.0,
      1.1-3.6; prethreshold/threshold: 1.9, 1.2-3.0; plus disease: 1.8, 1.1-2.9).
      Estimates are similar for a low pH for zone 1 (2.1, 1.2-3.8),
      prethreshold/threshold (1.8, 1.1-2.8), but did not quite achieve statistical
      significance for ROP stage 3, 4, or 5 (1.4, 0.9-2.0) and plus disease (1.5, 0.9
      2.4). A PaO(2) in the highest quartile for GA on at least 2 of the first 3
      postnatal days was associated with a doubling of the risk of ROP in zone 1 (2.5,
      1.4-4.4) and of prethreshold/threshold disease (2.1, 1.4-3.3), a 70% risk
      increase for plus disease (1.7, 1.04-2.8), while a 40% risk increase for ROP
      stage 3 or higher did not achieve statistical significance (1.4, 0.96-2.0).
      CONCLUSION: Infants exposed to high PCO(2), low pH and high PaO(2) appear to be
      at increased risk of more severe ROP.

PMID- 20689333
TI  - Physical and physiological effects on otoacoustic emissions in hypobaric hypoxia.
AB  - Tinnitus and dizziness are symptoms of acute mountain sickness. We investigated
      the mechanism by which high altitude (i.e. hypobaric hypoxia) affects inner ear
      function by measuring transient evoked otoacoustic emissions (TEOAE) and
      distortion product otoacoustic emissions (DPOAE) under conditions of normobaric
      normoxia (1,013 hPa; 760 mm Hg) and hypobaric hypoxia (540 hPa; 405 mm Hg). The
      possibility that air pressure effects on the eustachian tube impacted our
      findings was excluded by the use of tympanograms. The nonphysiological effects of
      hypobaric hypoxia on TEOAE and DPOAE were also assessed using an ear simulator.
      Under conditions of hypobaric hypoxia, both TEOAE and DPOAE levels were reduced.
      The amount of reduction that occurred was approximately 4 dB in the total echo
      power and signal-to-noise ratio of the TEOAE, and in the 2f(1) - f(2) element
      level of the DPOAE. Stimulus levels that were measured using an ear simulator
      were also reduced by approximately 4 dB under conditions of hypobaric hypoxia.
      These results do not indicate that stimulus levels affected TEOAE and DPOAE
      levels because these levels were actually only slightly affected by changes in
      the stimulus level. Instead, this reduction was likely due to the
      nonphysiological hypobaric effects of the sound pressure emitted from the
      tympanic membrane. We conclude that the impact of hypobaric hypoxia on cochlear
      function was negligible up to pressures of 540 hPa.

PMID- 20689334
TI  - Apnea/hypopnea index in the evaluation of tongue base procedures: is it enough
      for the determination of surgical success?

PMID- 20689336
TI  - Psychological aspects of female patients with moderate-to-severe persistent
      allergic rhinitis.
AB  - BACKGROUND: Allergic rhinitis (AR) has been shown to impair social life and
      psychological functioning. The objective of our study was to explore the
      relationships between moderate-to-severe persistent AR and personality traits in
      non-psychiatric female outpatients. METHODS: Female subjects were assigned to the
      allergic (n = 52, 24 singletons and 28 non-singletons) or non-allergic group (n =
      28, 11 singletons and 17 non-singletons) on the basis of skin prick tests (SPT)
      and allergic symptoms. Individuals in this study were only allergic to
      Dermatophagoides pteronyssinus and/or D. farinae. The psychological aspects of
      the female subjects were assessed by using the Minnesota Multiphasic Personality
      Inventory (MMPI). RESULTS: The allergic group scored significantly higher than
      the non-allergic group on 6 clinical scales [hypochondriasis (Hs), depression
      (D), hysteria (Hy), psychasthenia (Pt), schizophrenia (Sc), social introversion
      (Si)] and 1 validity scale [infrequency (F)]. Analysis of female singleton
      outpatient MMPI profiles showed that allergic subjects scored significantly
      higher on D, Hy, masculinity/femininity (Mf), Pt, and F. In addition, the grade
      of skin index (resulting from an SPT) was positively correlated with T-scores on
      the Hs, Hy, Pt, and Sc scales. CONCLUSION: Women with moderate-to-severe
      persistent AR, especially singleton patients, show poorer psychological
      functioning, indicating the close relationship between moderate-to-severe
      persistent AR and psychological functioning.

PMID- 20689337
TI  - Indication of the side of delayed endolymphatic hydrops by vestibular evoked
      myogenic potential and caloric test.
AB  - OBJECTIVE: Delayed endolymphatic hydrops (DEH) can be clinically classified into
      ipsi- and contralateral types. This study aims to investigate the relationship
      between the results of vestibular evoked myogenic potential (VEMP) and caloric
      testing and the clinical type of DEH. METHODS: The data of 33 patients with DEH
      who underwent both VEMPs and caloric testing were retrospectively examined. The
      type of DEH was judged from its clinical and audiological course. Theasymmetry
      ratios of the VEMPs and canal paresis on the caloric test were measured. RESULTS:
      The results of VEMP and the caloric testing were consistent with the type of DEH
      in 61 and 76% of DEH patients, respectively. Combined use of VEMP and caloric
      testing correctly identified the type of DEH in 82% of patients. CONCLUSIONS: The
      combined use of VEMP and caloric testing can indicate the type of DEH at a
      reasonably high rate, but inconclusively.

PMID- 20689338
TI  - Management of maxillary sinus inverted papilloma via transnasal endoscopic
      anterior and medial maxillectomy.
AB  - OBJECTIVE: To introduce and evaluate the effectiveness and safety of transnasal
      endoscopic anterior and medial maxillectomy (TEAMM) in the treatment of Krouse
      stage III inverted papilloma (IP) originating from the maxillary sinus. METHODS:
      A retrospective chart review was performed for 33 patients with Krouse stage III
      IP undergoing TEAMM in our hospital between 2003 and 2008. RESULTS: Tumors were
      completely resected through TEAMM. Sixteen cases had type I TEAMM, during which
      the nasolacrimal duct was preserved; 17 had type II TEAMM, during which the
      nasolacrimal duct was resected. The inferior turbinate was partially preserved in
      26 cases. Patients were followed for a mean of 40.4 months. Recurrence developed
      in 2 patients, dry nose syndrome in 5 patients, and epiphora in 1 patient.
      Squamous cell carcinoma occurred in 1 patient. CONCLUSIONS: TEAMM is an effective
      and safe technique in the management of Krouse stage III IP and provides good
      exposure of operative cavities during follow-up.

PMID- 20689339
TI  - Adhesion-induced drug resistance in leukemia stem cells.
AB  - The co-culture of TF-1 leukemia cells and MS-5 stromal cells produces a
      cobblestone area which partially mimics the leukemia stem cell niche. The
      adhering leukemia cells are shown to become less sensitive to cytarabine,
      etoposide and daunorubicin. These changes are associated with an increased
      proportion of the G0/G1 phase, increased upregulation of cyclin-dependent kinase
      inhibitors, and increased levels of Bcl-2, but not with any change in the
      expression of BAX or drug transporters such as ABCG2 and MDR1, compared to
      monocultured leukemic cells. In addition, we demonstrate using a bioimaging
      technique that daunorubicin accumulates in the lysosomes of the adherent leukemic
      cells and that V-ATPase is activated. These findings suggest that adhesion alone
      can lead to drug resistance in leukemic stem cells by various mechanisms.

PMID- 20689340
TI  - Effect of ramipril alone compared to ramipril with eplerenone on diabetic
      nephropathy in streptozocin-induced diabetic rats.
AB  - BACKGROUND/AIMS: We studied the effect of the combined treatment with an
      angiotensin-converting enzyme (ACE) inhibitor (ramipril) and eplerenone compared
      with ramipril alone in streptozocin-induced diabetic rats. METHODS: Wistar rats
      were divided into 4 groups: nondiabetic controls, streptozocin-treated diabetic
      rats (50 mg/kg), diabetic rats receiving ramipril (1 mg/kg) and diabetic rats
      treated with the combination of ramipril (1 mg/kg) and eplerenone (100 mg/kg) for
      8 weeks. Our model produced early-stage diabetic nephropathy. RESULTS: The
      diabetic rats developed polyuria, proteinuria, hyperfiltration (assessed by
      creatinine clearance) and histopathological evidence of renal injury including
      glomerular hypertrophy and mesangial expansion. Ramipril reduced proteinuria but
      its combination with eplerenone did not produce any greater benefit. Both
      treatment approaches prevented glomerular hypertrophy. Addition of eplerenone to
      ramipril prevented glomerular hyperfiltration. CONCLUSION: Whether eplerenone
      should be used in addition to an ACE inhibitor or an angiotensin receptor blocker
      at an early stage of diabetic nephropathy remains questionable.

PMID- 20689341
TI  - Oral protein therapy for the future - transport of glycolipid-modified proteins:
      vision or fiction?
AB  - The reliable and early diagnosis of common complex multifactorial diseases
      depends on the individual determination of all (or as many as possible)
      polymorphisms of each susceptibility gene together with amount and type of the
      corresponding gene products and their downstream effects, including the synthesis
      and flux of metabolites and regulation of signalling processes. In addition, this
      system's biology-driven personalized diagnosis must be accompanied by options for
      personalized reliable and early therapy. In the mid-term, the direct substitution
      or inhibition of the proteins encoded by the corresponding defective gene
      products of the susceptibility genes exerting lower or higher activity by
      administration of the 'normal' proteins or inhibitory antibodies, respectively,
      seems to be most promising. The critical hurdle of oral bioavailability as well
      as transport into the cytoplasm of the target cells, if required, could be
      overcome by therapeutic proteins with carboxy-terminal modification by
      glycosylphosphatidylinositol (GPI). This may be deduced from recent experiments
      with rat adipocytes. Here this membrane-anchoring glycolipid structure induces
      the sequential transport of proteins from special regions of the plasma membrane
      via the surface of intracellular lipid droplets to special membrane vesicles,
      which are finally released from the adipocytes together with the associated GPI
      proteins. It remains to be studied whether similar molecular mechanisms operate
      in intestinal epithelial cells and may enable the transport of GPI proteins from
      the intestinal lumen into the blood stream. If so, modification of proteins
      encoded by (combinations of) susceptibility genes with GPI could significantly
      facilitate the personalized therapy of common diseases on the basis of 'inborn'
      safety, efficacy, rapid realization and oral application.

PMID- 20689342
TI  - The role of peroxisome proliferator-activated receptor-gamma and estrogen
      receptors in genistein-induced regulation of vascular tone in female rat aortas.
AB  - BACKGROUND: Genistein (GST) is a phytoestrogen that binds estrogen receptors (ER)
      to produce a protective cardiovascular effect. It also has been shown binding
      peroxisome proliferator-activated receptor-gamma (PPAR-gamma). METHODS: In the
      present study, we assessed the role of PPAR-gamma and ER in GST-mediated
      regulation of vascular tone in female rat aortas by in vitro tension measurement,
      immunohistochemistry, immunofluorescence, immunoprecipitation and Western blot
      analysis. RESULTS: In aortas pretreated with GW9662 (inhibitor of PPAR-gamma),
      ICI182780 (inhibitor of ER) and a combination of GW9662 and ICI182780, the
      magnitudes of GST-induced dilatation were attenuated. N(G)-nitro-L-arginine
      methyl ester had a similar effect. ER-beta and PPAR-gamma colocalized in all 3
      layers of the aortas, while ER-alpha and PPAR-gamma colocalized only in the
      vascular endothelium and adventitia. In GST-treated whole-cell protein samples,
      we demonstrated coimmunoprecipitation of ER-beta (not ER-alpha) and PPAR-gamma.
      The expression of ER-beta and PPAR-gamma in nuclear protein from GST-treated
      samples increased, which was partially reversed by either GW9662 or ICI182780 and
      more efficiently reversed using a combination of GW9662 and ICI182780.
      CONCLUSION: Our findings suggest that GST can relax phenylephrine-induced
      vascular contraction in female rat aortas, which is mediated by PPAR-gamma and ER
      beta.

PMID- 20689343
TI  - Behavioural effects of co-administration of delta9-tetrahydrocannabinol with
      fluoxetine in rats.
AB  - Previous studies have suggested panic induced by cannabinoids may be potentiated
      by concurrently using selective serotonin reuptake inhibitors. We therefore
      tested for panic and anxiety-related behaviour in rats coadministered with the
      selective serotonin reuptake inhibitor fluoxetine hydrochloride and the CB1
      agonist delta9-tetrahydrocannabinol. Although each drug alone elicited behaviours
      consistent with previous studies, we did not find that coadministration of these
      drugs potentiated or reduced the effects of either drug alone. Specifically,
      fluoxetine treatment did not cause any increase in freezing behaviour, decrease
      in social interaction or exploration in an adverse environment, change preference
      for outer or inner zones, or modulate rearing behaviour in rats receiving delta9
      tetrahydrocannabinol.

PMID- 20689344
TI  - Effects of adenosine A(2A) and A(2B) receptor activation on signaling pathways
      and cytokine production in human uroepithelial cells.
AB  - AIMS: adenosine A(2A) and A(2B) receptor subtypes have both been implicated in
      the modulation of inflammation. We examined adenosine A(2A) and A(2B) receptor
      expression, signaling pathways and the effect of adenosine A(2A) and A(2B)
      receptor activation on the uropathogenic Escherichia coli (UPEC)-stimulated IL-8
      response in human uroepithelial cells (UROtsa). METHODS: receptor expression was
      examined by RT-PCR and Western blot, and IL-8 production, intracellular cAMP
      levels and phosphoproteins were measured by ELISA, EIA and multiplex immunoassay,
      respectively. RESULTS: the adenosine A(1), A(2A) and A(2B) receptor subtypes were
      detected in UROtsa cells. The adenosine A(2A) receptor agonist CGS 21680 did not
      stimulate cAMP production but CREB phosphorylation was slightly increased. The
      adenosine A(2) receptor agonist CPCA induced a pronounced cAMP and CREB response.
      Furthermore, CGS 21680 but not CPCA decreased ERK 1/2 and STAT3 phosphorylation.
      UPEC infection stimulated the host IL-8 production but CPCA or CGS 21680 did not
      affect UPEC-evoked IL-8 production. CONCLUSIONS: our data identified differences
      in signaling pathways evoked by adenosine A(2A) and A(2B) receptor activation.
      Activation of the adenosine A(2A) receptor inhibited STAT3 and ERK 1/2
      phosphorylation, while the cAMP-CREB pathway was induced by adenosine A(2B)
      receptor activation. No anti- or proinflammatory effects were found for
      uroepithelial adenosine A(2A) or A(2B) receptors.

PMID- 20689345
TI  - The functional antiopioid action of the ventrolateral periaqueductal gray
      nociceptin/orphanin FQ and nociceptin receptor system underlies DAMGO analgesic
      tolerance.
AB  - Nociceptin/Orphanin FQ (N/OFQ) counteracts supraspinal opioid effects and plays a
      role in antinociceptive morphine tolerance. Therefore, in the present study, the
      selective mu-opioid agonist [D-Ala(2)-NMe-Phe(4)-Gly-ol(5)]-enkephalin (DAMGO)
      was used. Repeated injection of DAMGO (1 microg/ 1 microl) into the ventrolateral
      periaqueductal gray (vlPAG), a key site for the development of opioid tolerance,
      induced analgesia that lasted up to 3 days. In DAMGO-tolerant rats, injection of
      the N/OFQ antagonist (+/-)-J 113397 (4 microg/1 microl), into the same site,
      restored the antinociceptive effect of DAMGO. If (+/-)-J 113397 treatment
      preceded each DAMGO injection, tolerance did not develop. Inhibition of N/OFQ
      signaling can reverse and prevent the development of DAMGO tolerance in the
      vlPAG. The results confirm that N/OFQ acts as a functional opioid antagonist.

PMID- 20689346
TI  - An unusual form of occipitocervical assimilation presenting with spastic
      tetraparesis in a child.
AB  - A diagnosis of 'cerebral palsy' in childhood is relatively common. Abnormalities
      of the upper cervical spine causing spinal cord compression are rare, but can be
      a cause of symptoms and signs that may otherwise be attributed to brain injury
      acquired during development. We present an interesting case of a congenital
      abnormality of the atlas causing severe cervical spinal cord compression in a 9
      year-old child, together with a discussion of the relevant aspects of spinal
      development and a review of the literature.

PMID- 20689347
TI  - Simultaneous middle fossa arachnoid cyst and ambient cistern epidermoid cyst:
      case report and endoscope-assisted microsurgical management.
AB  - Simultaneous occurrence of dual intracranial pathology is very rare. Most of such
      reported cases occur in the setting of a genetic or hereditary predisposing
      condition like neurofibromatosis. Though some cases of coexistence of multiple
      intracranial pathologies have been reported, occurrence of an arachnoid and
      epidermoid cyst in the same patient has never been reported. A 16-year-old boy
      was referred to us with a diagnosis of left temporal arachnoid cyst. Careful
      review of the MRI showed the presence of 2 different signal intensities with
      restricted diffusion in the cyst in the ambient cistern and normal diffusion in
      the cyst anterior to the temporal tip suggesting the presence of an arachnoid
      cyst adjacent to an epidermoid cyst which was managed using endoscope-assisted
      microsurgical transcranial surgery. The possibility of such an association could
      be explained based on the congenital origin of both lesions. Diffusion-weighted
      imaging can be invaluable in unraveling such a relationship.

PMID- 20689348
TI  - Endodermal cyst of the oculomotor nerve.

PMID- 20689349
TI  - Interview-based ratings of somatic and cognitive symptoms of depression and their
      impact on cardiovascular prognosis.

PMID- 20689350
TI  - Receptive music therapy for the treatment of depression: a proof-of-concept study
      and prospective controlled clinical trial of efficacy.

PMID- 20689351
TI  - Clinical implications of the cytokine hypothesis of depression: the association
      between use of statins and aspirin and the risk of major depression.

PMID- 20689352
TI  - Depression, burnout and effort-reward imbalance among psychiatrists.

PMID- 20689353
TI  - Optimal functioning: contribution of self-efficacy beliefs to positive
      orientation.

PMID- 20689354
TI  - The Korean prediction model for adolescents' future smoking intentions.
AB  - OBJECTIVES: The purpose of this study was to develop a prediction model for
      future smoking intention among Korean adolescents aged 13 to 15 in order to
      identify the high risk group exposed to future smoking. METHODS: The data was
      collected from a total of 5940 students who participated in a self-administrated
      questionnaire of a cross-sectional school-based survey, the 2004 Korea Global
      Youth Tobacco Survey. Chi-square tests and logistic regression analyses were
      carried out to identify the relevant determinants associated with intentions of
      adolescents' future smoking. Receiver Operation Characteristic (ROC) assessment
      was applied to evaluate the explanation level of the developed prediction model.
      RESULTS: 8.4% of male and 7.2% of female participants show their intentions of
      future smoking. Among non-smoking adolescents; who have past smoking experience
      [odds ratio (OR) 2.73; 95% confidence interval (CI) 1.92 - 3.88]; who have
      intentions of smoking when close friends offer a cigarette (OR 31.47; 95% CI =
      21.50 - 46.05); and who have friends that are mostly smokers (OR 5.27; 95% CI =
      2.85 - 9.74) are more likely to be smokers in the future. The prediction model
      developed from this study consists of five determinants; past smoking experience;
      parents smoking status; friends smoking status; ownership of a product with a
      cigarette brand logo; and intentions of smoking from close friends' cigarette
      offer. The area under the ROC curve was 0.8744 (95% CI=0.85 - 0.90) for current
      non-smokers. CONCLUSIONS: For efficiency, school-based smoking prevention
      programs need to be designed to target the high risk group exposed to future
      smoking through the prediction model developed by the study, instead of
      implementing the programs for all the students.

PMID- 20689355
TI  - Factors related to perceived life satisfaction among the elderly in South Korea.
AB  - OBJECTIVES: This study attempted to explore the aging phenomena that now
      characterize much of Korean society, and assessed issues associated with the life
      satisfaction experienced during the process of aging. METHODS: By employing the
      National Survey on the State of Life and the Desire for Welfare of the Elderly,
      2004 in South Korea this study attempted to identify the factors that determine
      subjective life satisfaction among the elderly. The data utilized herein
      consisted of 3278 elderly people aged 65 years or older, from 9308 households.
      RESULTS: The results of analysis from the final model after the introduction of
      19 variables in 8 factors showed statistically similar explanatory power in men
      (adj. R2=0.320) and in women (adj. R2=0.346). We found that economic condition
      was the most influential factor in both men (B=0.278) and women (B=0.336) except
      perceived health condition variables. The second most influential variable in
      life satisfaction was health checkups in men (B=0.128) and degree of nutritional
      diet in women (B=0.145). Those who had experience with chronic diseases also
      reported significantly lower perceived life satisfaction and this was
      particularly true of women. CONCLUSIONS: The aging society requires an
      understanding of the lives of elderly individuals. This study explored factors
      associated with life satisfaction in old age by using a life satisfaction model.
      The success of an aging society begins with an accurate understanding of the
      elderly, and thus political attention will need to be focused on this matter.

PMID- 20689356
TI  - Assessment of di (2-ethylhexyl) phthalate exposure by urinary metabolites as a
      function of sampling time.
AB  - OBJECTIVES: In most DEHP exposure assessment studies, single spot urine sample
      was used. It could not compare the exposure level among studies. Therefore, we
      are going to represent the necessity of selection of proper sampling time of spot
      urine for assessing the environmental DEHP exposure, and the association urinary
      DEHP metabolites with steroid hormones. METHODS: We collected urine and plasma
      from 25 men. The urine sampling times were at the end of the shift (post-shift)
      and the next morning before the beginning of the shift (pre-shift). Three
      metabolites of DEHP {mono(2-ethylhexyl) phthalate [MEHP], mono-(2-ethyl-5
      hydroxyhexyl)phthalate [MEHHP], and mono(2-ethyl-5-oxohexyl)phthalate [MEOHP]} in
      urine were analyzed by HPLC/MS/MS. Plasma luteinzing hormone, follicle
      stimulating hormone, testosterone, and 17beta-estradiol were measured at pre
      shift using a ELISA kit. A log-transformed creatinine-adjusted urinary MEHP,
      MEHHP, and MEOHP concentration were compared between the post- and pre-shift. The
      Pearson's correlation was calculated to assess the relationships between log
      transformed urinary MEHP concentrations in pre-shift urine and hormone levels.
      RESULTS: The three urinary metabolite concentrations at post-shift were
      significantly higher than the concentrations in the pre-shift (p<0.0001). The
      plasma hormones were not significantly correlated with log-transformed creatinine
      - adjusted DEHP metabolites. CONCLUSIONS: To assess the environmental DEHP
      exposure, it is necessary to select the urine sampling time according to the
      study object. There were no correlation between the concentration of urinary DEHP
      metabolites and serum hormone levels.

PMID- 20689357
TI  - [Associated factors of impaired fasting glucose in some Korean rural adults].
AB  - OBJECTIVES: This study was performed to investigate the prevalence of impaired
      fasting glucose (IFG) and its related characteristics among healthy adults in
      some Korean rural areas. METHODS: We conducted a cross-sectional study using the
      data from 1352 adults who were over the age 40 and under the age 70 and who were
      free of diabetes mellitus (DM), cardiovascular diseases and other diseases and
      who participated in a survey conducted as part of the Korean Rural Genomic Cohort
      Study. IFG was defined as a serum fasting glucose level between 100 and 125
      mg/dL. RESULTS: The prevalence of IFG was 20.4% in men, 15.5% in women and 12.7%
      overall. Multivariate logistic regression analysis demonstrated that the
      independent risk factors for IFG were male gender, having a family history of DM,
      the quartiles of gamma glutamyltransferase and high sensitive C-reactive protein
      and the waist circumference. The homeostatis model assessment for insulin
      resistance was very strongly associated with IFG. The prevalence of metabolic
      syndrome (MS) and MS components was higher in the subjects with IFG then in those
      with normal fasting glucose (NFG). CONCLUSIONS: The result of study could supply
      evidence to find the high risk population and to determine a strategy for
      treating IFG. Further research is needed to explain the causal relationship and
      mechanisms of IFG.

PMID- 20689358
TI  - [Relationship between status of physical and mental function and quality of life
      among the elderly people admitted from long-term care insurance].
AB  - OBJECTIVES: This study was performed to determine the levels of quality of life
      (QOL) according to the grade of long-term care service for the elderly people who
      were admitted from long-term care insurance, and to reveal its association with
      the physical and mental functioning such as the Activity of Daily Living (ADL),
      the Instrumental Activity of Daily Living (IADL), the Center for Epidemiologic
      Studies Depression Scale (CES-D), and the Mini-Mental State Examination-Korean
      version (MMSE-K). METHODS: The interviews were performed during the period from
      March 1 to May 31, 2009, for 958 elderly people in urban and rural areas. The
      questionnaire items included various indices such as the ADL, IADL, CES-D, and
      MMSE-K, as independent variables and the index of QOL, as the dependent ones. For
      statistical analysis, t-tests were used for the mean scores of QOL according to
      gender and the grade of long-term care services, and Spearman's correlation was
      used for each variable. The effects of physical and mental functioning for QOL
      were assessed by covariance structure analysis. The statistical significance was
      set at p<0.05. RESULTS: The mean scores of QOL among all the subjects was 55.4 +/
      15.62 (Grade I: 49.7 +/- 14.17, Grade II: 56.8 +/- 14.62, Grade III: 59.4 +/-
      16.36), and it was lower according to the higher grade of long-term care
      insurance. In terms of the correlation matrix of the QOL and the physical and
      mental function factors, the QOL showed positive correlation with the ADL, IADL
      and MMSE-K, while it had negative correlation with depression. On the analysis of
      covariance, mental functioning (depression and the MMSE-K) had a greater
      influence on the level of QOL than the physical functioning (ADL and IADL).
      CONCLUSIONS: The level of the QOL in the elderly people who were admitted from
      long-term care insurance was lower according to higher the grade of long-term
      care insurance. Also, the mental functioning (depression and MMSE-K) was more
      influential on the level of the QOL than the physical functioning (ADL and IADL).

PMID- 20689359
TI  - [Association between socioeconomic status and all-cause mortality after breast
      cancer surgery: nationwide retrospective cohort study].
AB  - OBJECTIVES: This study aims to evaluate and explain the socioeconomic
      inequalities of all-cause mortality after breast cancer surgery in South Korea.
      METHODS: This population based study included all 8868 females who underwent
      radical mastectomy for breast cancer between January 2002 and June 2003. Follow
      up for mortality continued from January 2002 to June 2006. The patients were
      divided into 4 socioeconomic classes according to their socioeconomic status as
      defined by the National Health Insurance contribution rate. The relationship
      between socioeconomic status and all-cause mortality after breast cancer surgery
      was assessed using the Cox proportional hazards model with adjusting for age, the
      Charlson's index score, emergency hospitalization, the type of hospital and the
      hospital ownership. RESULTS: Those in the lowest socioeconomic status group had a
      significantly higher hazard ratio of 2.09 (95% CI =1.50 - 2.91) compared with
      those in the highest socioeconomic group after controlling for all the
      identifiable confounding variables. For all-cause mortality after radical
      mastectomy, all the other income groups showed significantly higher 3-year
      mortality rates than did the highest income group. CONCLUSIONS: The socioeconomic
      status of breast cancer patients should be considered as an independent
      prognostic factor that affects all-cause mortality after radical mastectomy, and
      this is possibly due to a delayed diagnosis, limited access or minimal treatment
      leading to higher mortality. This study may provide tangible support to intensify
      surveillance and treatment for breast cancer among low socioeconomic class women.

PMID- 20689360
TI  - [Estimating the socioeconomic costs of alcohol drinking among adolescents in
      Korea].
AB  - OBJECTIVES: The purpose of this study was to estimate the socioeconomic costs
      resulting from alcohol drinking among adolescents as of 2006 from a societal
      perspective. METHODS: The costs were classified into direct costs, indirect
      costs, and other costs. The direct costs consisted of direct medical costs and
      direct non-medical costs. The indirect costs were computed by future income
      losses from premature death, productivity losses from using medical services and
      reduction of productivity from drinking and hangover. The other costs consisted
      of property damage, public administrative expenses, and traffic accident
      compensation. RESULTS: The socioeconomic costs of alcohol drinking among
      adolescents as of 2006 were estimated to be 387.5 billion won (0.05% of GDP). In
      the case of the former, the amount included 48.25% for reduction of productivity
      from drinking and hangover, 39.38% for future income losses from premature death,
      and 6.71% for hangover costs. CONCLUSIONS: The results showed that the
      socioeconomic costs of alcohol drinking among adolescents in Korea were a serious
      as compared with that of the United States. Therefore, the active interventions
      such as a surveillance system and a prevention program to control adolescents
      drinking by government and preventive medicine specialist are needed.

PMID- 20689361
TI  - [Socioeconomic costs of food-borne disease using the cost-of-illness model:
      applying the QALY method].
AB  - OBJECTIVES: This study estimated the annual socioeconomic costs of food-borne
      disease in 2008 from a societal perspective and using a cost-of-illness method.
      METHODS: Our model employed a comprehensive set of diagnostic disease codes to
      define food-borne diseases with using the Korea National Health Insurance (KNHI)
      reimbursement data. This study classified the food borne illness as three types
      of symptoms according to the severity of the illness: mild, moderate, severe. In
      addition to the traditional method of assessing the cost-of-illness, the study
      included measures to account for the lost quality of life. We estimated the cost
      of the lost quality of life using quality-adjusted life years and a visual analog
      scale. The direct cost included medical and medication costs, and the non-medical
      costs included transportation costs, caregiver's cost and administration costs.
      The lost productivity costs included lost workdays due to illness and lost
      earnings due to premature death. RESULTS: The study found the estimated annual
      socioeconomic costs of food-borne disease in 2008 were 954.9 billion won (735.3
      billion won-996.9 billion won). The medical cost was 73.4 - 76.8% of the cost,
      the lost productivity cost was 22.6% and the cost of the lost quality of life was
      26.0%. CONCLUSIONS: Most of the cost-of-illness studies are known to have
      underestimated the actual socioeconomic costs of the subjects, and these studies
      excluded many important social costs, such as the value of pain, suffering and
      functional disability. The study addressed the uncertainty related to estimating
      the socioeconomic costs of food-borne disease as well as the updated cost
      estimates. Our estimates could contribute to develop and evaluate policies for
      food-borne disease.

PMID- 20689362
TI  - [Suggestions for increasing physical activity levels of Korean older adults: a
      public health perspective].
AB  - 2010 is the year when the Korean baby boomer generation faces retirement. With
      the need for affective strategies to keep this population healthy, the government
      has placed much effort to increase the regular physical activity (PA) level of
      older adults. Yet the prevalence of active seniors is still relatively low. This
      paper reviews the recent government strategies and efforts to enhance the
      physical activity levels of older adults and the PA programs provided in the
      community settings by major organizations and institutions. In addition, the
      problems of the current approaches are shown, and based on a review, the author
      provides five suggestions for promoting the PA level of older adults as follows.
      First, specific physical activity goals and objectives for older adults should be
      included in the National Health Plan 2020. Second, the recommendations for PA for
      seniors, which include a proper intensity, duration and frequency of exercise,
      should be provided. Third, the role of organizations and institutions should be
      rearranged for the proper dissemination of government provided community-based
      exercise programs. Fourth, a standard quality-control system should be provided,
      and finally, an evidence-based exercise program, which should be specifically
      created for the older Korean population, should be developed. Physical activity
      offers opportunities for people to extend the years of their active independent
      life and reduce functional limitations. To maximize the effects of government
      efforts to promote PA for seniors, we feel the comments provided in this paper
      should be closely examined.

PMID- 20689363
TI  - Association between green tea consumption and lung cancer risk.
AB  - Green tea is a popular beverage and its health benefits are well known. However,
      inconsistent results have been reported in observational studies concerning the
      association between green tea consumption and the lung cancer risk. In this
      commentary, several methodological issues underlying the measurement of tea
      exposure are highlighted. The recommendations should be useful for designing and
      planning prospective cohort studies to ascertain the protective effect of green
      tea against lung cancer.

PMID- 20689364
TI  - Molecular imaging of membrane proteins and microfilaments using atomic force
      microscopy.
AB  - Atomic force microscopy (AFM) is an emerging technique for a variety of uses
      involving the analysis of cells. AFM is widely applied to obtain information
      about both cellular structural and subcellular events. In particular, a variety
      of investigations into membrane proteins and microfilaments were performed with
      AFM. Here, we introduce applications of AFM to molecular imaging of membrane
      proteins, and various approaches for observation and identification of
      intracellular microfilaments at the molecular level. These approaches can
      contribute to many applications of AFM in cell imaging.

PMID- 20689365
TI  - Does brachytherapy improve survival in addition to external beam radiation
      therapy in patients with high risk stage I and II endometrial carcinoma?
AB  - INTRODUCTION: The benefit of adjuvant external beam radiation therapy (EBRT) in
      combination with intravaginal brachytherapy (BT) in stage I and II endometrial
      adenocarcinoma remains controversial. We evaluated the effect of adjuvant EBRT
      and combined EBRT + BT on overall survival and relative survival within a large
      US population database. METHODS: We performed an analysis of retrospective data
      from the Surveillance, Epidemiology, and End Results (SEER) program of the US
      National Cancer Institute from January 1, 1998 to December 31, 2005. A total of
      3395 patients with stages IB, IC, and II node-negative endometrial adenocarcinoma
      comprised the population. Overall survival (OS) and relative survival (RS) curves
      were constructed via the Kaplan-Meier method and subgroups were compared via
      stratified log-rank test within T stage/grade combinations. Cox proportional
      hazards modeling was performed to evaluate the effect of multiple variables.
      RESULTS: EBRT alone was used in 2128 patients (62.7%) and 1267 patients (37.3%)
      received a combination of EBRT + BT. Higher grade, black race, older age at
      diagnosis, and later year of diagnosis are associated with worse overall
      survival, while lymphadenectomy is associated statistically with improved
      survival. The addition of BT revealed no statistically significant effect on OS.
      CONCLUSIONS: This large population-based study revealed no improvement in OS or
      RS with the addition of BT to EBRT in high risk stage I and stage II endometrial
      cancer. Although specific patient cohorts may benefit from combined EBRT and BT,
      additional analysis is warranted to further elucidate optimal treatment
      strategies for adjuvant radiotherapy based on specific clinical and pathologic
      features.

PMID- 20689366
TI  - When more is worse in clinical research and clinical practice.

PMID- 20689367
TI  - HPV in head and neck cancers among 5-year survivors.

PMID- 20689368
TI  - Healthier homes for a healthier nation.

PMID- 20689370
TI  - How much evidence is enough? Assessing home asthma research.

PMID- 20689369
TI  - Housing interventions and control of asthma-related indoor biologic agents: a
      review of the evidence.
AB  - Subject matter experts systematically reviewed evidence on the effectiveness of
      housing interventions that affect health outcomes, primarily asthma, associated
      with exposure to moisture, mold, and allergens. Three of the 11 interventions
      reviewed had sufficient evidence for implementation: multifaceted, in-home,
      tailored interventions for reducing asthma morbidity; integrated pest management
      to reduce cockroach allergen; and combined elimination of moisture intrusion and
      leaks and removal of moldy items to reduce mold and respiratory symptoms. Four
      interventions needed more field evaluation, 1 needed formative research, and 3
      either had no evidence of effectiveness or were ineffective. The 3 interventions
      with sufficient evidence all applied multiple, integrated strategies. This
      evidence review shows that selected interventions that improve housing conditions
      will reduce morbidity from asthma and respiratory allergies.

PMID- 20689371
TI  - Housing interventions and control of health-related chemical agents: a review of
      the evidence.
AB  - Subject matter experts systematically reviewed evidence on the effectiveness of
      housing interventions that affect health outcomes associated with exposure to
      chemical agents, such as pesticides, lead, volatile organic compounds, as well as
      the radon gas. Particulates were also examined, and the role of ventilation on
      exposures was assessed. The review included both published literature and peer
      reviewed reports from the US Environmental Protection Agency. Four of the 14
      interventions reviewed had sufficient evidence to demonstrate their effectiveness
      and are ready for implementation: radon air mitigation by using active soil
      depressurization systems, integrated pest management to reduce exposures to
      pesticides, smoke-free home policies making indoor areas smoke-free (ie, no
      smoking allowed anywhere at any time), and residential lead hazard control. Four
      interventions needed more field evaluation, 3 needed formative research, and 3
      either had no sufficient evidence of effectiveness or had evidence the
      interventions were ineffective. This evidence review shows that housing
      improvements are likely to help reduce radon-induced lung cancer, cardiovascular
      mortality related to secondhand smoke, and neurological effects from exposure to
      pesticides and lead paint. Investing in housing interventions may yield important
      savings from reduced disease and injury from avoidable exposures to chemical
      agents.

PMID- 20689372
TI  - From healthy homes to health equity.

PMID- 20689373
TI  - Housing interventions and control of injury-related structural deficiencies: a
      review of the evidence.
AB  - Subject matter experts systematically reviewed evidence on the effectiveness of
      housing interventions that affect safety and injury outcomes, such as falls, fire
      related injuries, burns, drowning, carbon monoxide poisoning, heat-related
      deaths, and noise-related harm, associated with structural housing deficiencies.
      Structural deficiencies were defined as those deficiencies for which a builder,
      landlord, or home-owner would take responsibility (ie, design, construction,
      installation, repair, monitoring). Three of the 17 interventions reviewed had
      sufficient evidence for implementation: installed, working smoke alarms; 4-sided
      isolation pool fencing; and preset safe hot water temperature. Five interventions
      needed more field evaluation, 8 needed formative research, and 1 was found to be
      ineffective. This evidence review shows that housing improvements are likely to
      help reduce burns and scalds, drowning in pools, and fire-related deaths and
      injuries.

PMID- 20689375
TI  - A systematic review of housing interventions and health: introduction, methods,
      and summary findings.
AB  - Subject matter experts systematically reviewed evidence on the effectiveness of
      specific housing interventions in improving health. The panelists reviewed
      housing interventions associated with exposure to biological and chemical agents,
      structural injury hazards, and community-level interventions. Intervention
      studies were grouped together according to recommendations in the Guide to
      Community Preventive Services, which identifies similarities in the type of
      intervention, its delivery and setting, and the target population. Review
      panelists found that 11 interventions had sufficient evidence of effectiveness,
      15 required more field evaluation, 19 needed formative research, and 7 either had
      no evidence of effectiveness or were ineffective. Although many housing
      conditions are associated with adverse health outcomes, sufficient evidence now
      shows that specific housing interventions can improve certain health outcomes.
      The results of these evidence reviews can inform a robust agenda for widespread
      implementation and further research. This article highlights the project's
      research methods and summary findings, and its companion articles detail the
      evidence reviews for specific housing interventions.

PMID- 20689374
TI  - Housing interventions at the neighborhood level and health: a review of the
      evidence.
AB  - A panel of subject matter experts systematically reviewed evidence linking
      neighborhood-level housing interventions, such as housing programs or policies,
      to health outcomes. One of the 10 interventions reviewed--the Housing Choice
      Voucher Program--had sufficient evidence for implementation or expansion. The
      evidence showed that voucher holders are less likely to suffer from overcrowding,
      malnutrition due to food insecurity, and concentrated neighborhood poverty than
      non-voucher holders. Of the other reviewed interventions, 2 needed more field
      evaluation and 7 needed more formative research. None were determined to be
      ineffective. Although many of the reviewed interventions lacked sufficient
      evidence for widespread implementation solely based on their health benefits,
      this evidence review shows that many interventions positively affect other areas
      of social, economic, and environmental well-being. Efforts to improve
      neighborhood environments and to maintain and increase the number of affordable
      housing units are critical to ensuring safe, healthy, and affordable housing for
      all people in the United States. Given that people of color disproportionately
      reside in high-poverty neighborhoods, neighborhood-level interventions may be
      particularly important in efforts to eliminate health disparities.

PMID- 20689377
TI  - The development of the residential Fire H.E.L.P. tool kit: a resource to protect
      homebound older adults.
AB  - This article describes the development of the Fire H.E.L.P. tool kit for training
      selected Meals On Wheels (MOW) staff in Texas to implement a fire safety program
      for homebound older adults. We used a formative evaluation approach during the
      tool kit's development, testing, and initial implementation stages. The tool kit
      includes instructional curricula on how to implement Fire H.E.L.P., a home
      assessment tool to determine a residence's smoke alarm needs, and fire safety
      educational materials. During the tool kit's pilot test, MOW participants showed
      enhanced fire safety knowledge and high levels of confidence about applying their
      newfound training skills. After the pilot test, MOW staff used the tool kit to
      conduct local training sessions, provide fire safety education, and install smoke
      alarms in the homes of older adults. We believe the approach used to develop this
      tool kit can be applied to education efforts for other, related healthy home
      topics.

PMID- 20689376
TI  - Making the transition from lead poisoning prevention to healthy homes: a
      qualitative study.
AB  - CONTEXT AND OBJECTIVE: The goal of this study was to create a guide for programs
      considering transition from Lead Poisoning Prevention to Healthy Homes. Healthy
      Homes programs are comprehensive, focusing on multiple residential housing
      hazards. This study focused on the Baltimore City Healthy Homes Division, which
      was selected by the Centers for Disease Control and Prevention to pilot the
      transition process. DESIGN, SETTING, AND PARTICIPANTS: For this qualitative
      study, data were collected through interviews with program staff from the
      Baltimore City Healthy Homes Division and followed up by focus groups with
      community members who received its services. Grounded theory procedures were used
      for data analysis. Interviews and focus groups were conducted in Baltimore City
      near the Health Department. Seventeen interviews were conducted with Baltimore
      City Healthy Homes Division staff. Three focus groups were held with 3 to 6
      community participants in each group. RESULTS: Findings for the study are
      arranged around an organizational framework for which transition from Lead
      Poisoning Prevention to Healthy Homes is the central phenomenon. Three general
      themes emerged: (1) programmatic changes; (2) policy changes; and (3)
      partnerships. Quotations from participating staff and community members provide
      supporting evidence for the results. CONCLUSIONS: Findings provide insight into
      the strengths and challenges of transition for 1 program. The study has
      implications for change on a national level as programs around the country
      transition to provide families with comprehensive Healthy Homes services.

PMID- 20689378
TI  - Healthy energy-efficient housing: using a one-touch approach to maximize public
      health, energy, and housing programs and policies.
AB  - Housing conditions such as leaky roofs, peeling paint, structural problems,
      chronic dampness, improperly vented combustion appliances, and poor ventilation
      can cause injury, illness, and increased energy consumption. Homes with moderate
      and severe housing hazards are more likely to be occupied by families with
      limited incomes because of the lack of affordable housing choices. As a result,
      children and older adults in these communities face disproportionate impacts from
      these housing hazards, including higher asthma and injury rates, greater
      prevalence of lead poisoning, and higher household energy burdens. Programs and
      policies addressing home health and energy issues have historically operated in
      categorical silos, which in turn cause fragmented service delivery and
      inefficient use of scarce resources by the agencies providing these services. A
      "one-touch" approach for home interventions that strategically integrates public
      health and energy efficiency has many potential direct and indirect benefits.
      Also, this approach plays an important role in housing policy due to the
      increasing support for green housing and residential energy efficiency.

PMID- 20689379
TI  - National Healthy Homes Training Center and Network: building capacity for healthy
      homes.
AB  - Recognizing the need to build a cadre of health care and housing professionals
      prepared to make homes healthier, in 2003, the US Centers for Disease Control and
      Prevention in partnership with the US Department of Housing and Urban Development
      launched the National Healthy Homes Training Center and Network (Training
      Center). Through a competitive process, the Centers for Disease Control and
      Prevention selected the National Center for Healthy Housing to host and manage
      the Training Center. The Training Center has flourished with additional support
      from US Environmental Protection Agency. The training incorporates interventions
      known to be most effective and helps to disseminate best practices. By 2010, it:
      developed a curriculum of 8 courses including 1 online course; trained more than
      6500 people; credentialed more than 380 people as Healthy Homes specialists;
      delivered more than 220 one- or two-day trainings in 40 states; grew from 5 to 25
      state or regional training partners covering 40 states; and created an extensive
      Web site of resources at www.healthyhomestraining.org.

PMID- 20689380
TI  - Estimates of costs for housing-related interventions to prevent specific
      illnesses and deaths.
AB  - Public health is embracing economic analyses in an effort to use limited
      resources in the most efficient manner. However, users of economic analyses in
      the public health arena should recognize the inherent strengths and weaknesses of
      different types of analysis, as well as understand how the inclusion or omission
      of certain costs or benefits might influence study results. For example, asthma
      is a chronic condition that can result in health care costs that accrue well
      beyond the duration of a housing intervention. Thus, an economic analysis that
      omits long-term health care costs can underestimate the total economic benefit of
      the housing intervention. This article contains reviews of economic articles on
      housing interventions published in PubMed, examines salient differences between
      studies, and discusses pertinent gaps in the literature. In addition, this
      article attempts to provide an overview of key economic evaluation methods in
      relation to housing interventions to a target audience of local and state public
      health practitioners. Specific housing-related health issues discussed include
      asthma, lead, and carbon monoxide poisoning and radon-related lung cancer.

PMID- 20689381
TI  - Federal agency support for healthy homes.
AB  - Numerous studies have demonstrated that housing interventions such as addressing
      structural deficiencies or lack of safety devices improve health. These
      successes, coupled with reports by health care and housing professionals of other
      health and safety issues in homes that they were unable to address, have renewed
      interest in promoting health by addressing unhealthy housing conditions--but with
      a holistic approach. The Centers for Disease Control and Prevention, US
      Department of Housing and Urban Development, and US Environmental Protection
      Agency fund programs to improve indoor air and drinking water quality and prevent
      childhood lead poisoning. All of these programs offer valuable lessons for
      designing more integrated programs. The federal agencies and their grantees have
      demonstrated that interagency collaboration is essential for successful outcomes.
      However, the Department of Housing and Urban Development, the Environmental
      Protection Agency, and the Centers for Disease Control recognize that no
      individual agency has all of the necessary resources or expertise to formulate
      national programs and policies and implement a national healthy homes agenda.
      Thus, they have come together with the US Department of Health and Human
      Services, the Department of Energy, the US Department of Agriculture, the
      National Institute of Standards and Technology, the National Institute of
      Environmental Health Sciences, and the Office of the Surgeon General to form an
      interagency working group to ensure that vigorous, healthy homes policies are
      implemented at federal, national, and community levels.

PMID- 20689382
TI  - Evaluation of a legislatively mandated influenza vaccination program for adults
      in Rhode Island, USA.
AB  - CONTEXT: There have been disruptions in influenza vaccine supply in the United
      States during the 2000-2001, 2001-2002, 2004-2005, and 2005-2006 influenza
      seasons. Some providers received limited or no vaccine, while others obtained
      their order in full, depending on with whom the order was placed. A state law was
      passed that mandates the Rhode Island Department of Health to include the
      purchase and distribution of influenza vaccine for adults in its immunization
      program. OBJECTIVE: To evaluate the first 2 years of the statewide adult
      influenza immunization program. DESIGN: We conducted key informant interviews of
      25 providers in 2008 and surveyed all enrolled providers in 2008 (year 1) and
      2009 (year 2). SETTING: State of Rhode Island. PARTICIPANTS: Physician practices
      and facilities that provide influenza vaccination to adults, including private
      practices, nursing homes, health centers, urgent care facilities, hospitals, mass
      immunizers, and businesses. INTERVENTION: Enrolled providers received influenza
      vaccines free and billed insurers, Medicare, and Medicaid for vaccine
      administration costs. MAIN OUTCOME MEASURES: Provider satisfaction with different
      program components and overall satisfaction. RESULTS: For year 1, there was
      higher satisfaction with enrollment, training, vaccine ordering, and vaccine
      shipment than with paperwork and claims. Of the survey respondents, 71% reported
      that the program paperwork was reasonable and 30% reported difficulties in
      receiving reimbursement. Satisfaction with the vaccination start date of October
      17, 2007, was 80%. There was high overall satisfaction (94%). In response to
      streamlining of reporting requirements and setting an earlier start date of
      October 7, 2008, for year 2, there was a significant increase in satisfaction
      with paperwork (89%) and with vaccination start date (90%). CONCLUSIONS: The
      findings may be useful in guiding the development of vaccination programs to
      provide influenza and other vaccines for adults at the state or national level.

PMID- 20689383
TI  - The impact of monitoring tuberculosis reporting delays in New York City.
AB  - Public health departments rely on the timely receipt of tuberculosis (TB) reports
      to promptly initiate patient management and contact investigations. In 2003, 43%
      of persons in New York City with confirmed or suspected TB were reported 4 or
      more days late. An intervention to increase the timeliness of TB reporting was
      initiated in 2004. A list of patients who were reported late and had a smear
      positive for acid-fast bacilli, a pathology finding consistent with TB, or who
      initiated 2 or more anti-TB medications was generated quarterly. Health care
      providers and laboratories were contacted to determine the reasons for reporting
      late and were educated on TB reporting requirements. To assess the effectiveness
      of the intervention, we evaluated the trend in delayed reports between 2003 and
      2006, using the Jonckheere-Terpstra test for trend. The proportion of patients
      who were reported late decreased from 43% (942/2183) in 2003 to 20% (386/1930) in
      2006 (Ptrend < .0001). There were improvements in reporting timeliness for all 3
      reporting criteria included in the evaluation and all provider types (all Ptrend
      < .0001); however, private providers consistently had a higher proportion of
      delayed reporting (22% reported late in 2006). This relatively simple
      intervention was very effective in improving the timeliness of TB reporting and
      could be utilized for other reportable diseases where prompt reporting is
      critical.

PMID- 20689384
TI  - Physical activity and obesity prevention in American Indian youth: the path
      forward.

PMID- 20689385
TI  - Childhood obesity in American Indians.
AB  - American Indian youth are affected disproportionately by the epidemic of obesity
      and its comorbidities compared with other ethnic groups in the United States.
      Before 10 years of age, 40% to 50% of Indian children of many communities are
      classified as either overweight or obese by modern definitions in contrast to
      data from a century ago in which Caucasian and Lakota children were equivalent in
      weight and body mass index. Multiple etiologies must be addressed to build
      programs to decrease the prevalence of childhood obesity. While awaiting
      definitive results from prevention and treatment trials, common-sense approaches
      such as encouraging healthy diets and increased activity are appropriate. A long
      term approach to the community is necessary to improve the health of Indian
      children: short-term programs that come and go along with varying personnel may
      not be accepted by the community. We have achieved acceptance in Native American
      communities, utilizing telecommunications to introduce a family directed program
      that is then modified and administered by members of the community to ensure that
      it is culturally acceptable.

PMID- 20689386
TI  - Youth-onset type 2 diabetes among american indians and alaska natives.
AB  - Youth-onset type 2 diabetes has emerged as a significant public health concern
      for American Indians and Alaska Natives. Data from the National Institutes of
      Health longitudinal epidemiological study among the Pima Indians of southern
      Arizona and the Indian Health Service continue to document a rising incidence and
      prevalence of type 2 diabetes among American Indian and Alaska Native youth.
      Although national trends related to lack of physical activity and to unhealthy
      nutrition behaviors have contributed to the epidemic, the adverse conditions
      created by poverty, social injustice, trauma, and cultural disruption are also
      important in understanding the underlying causes for this public health crisis.
      This adverse environment is likely to provide little support for healthy
      nutrition and physical activity behaviors as well as other diabetes self-care
      behaviors. Known risk factors from the Pima Indian studies, such as intrauterine
      exposure to diabetes, bottle-feeding, and obesity, provide a basis for worthwhile
      intervention strategies. In this article, the author will review the current
      literature on the epidemiology of youth-onset type 2 diabetes among American
      Indians and Alaska Natives, discuss causes for the diabetes epidemic among
      American Indians and Alaska Natives, review risk factors for youth-onset type 2
      diabetes in this population, and share promising youth physical activity
      promotion programs created and implemented specifically for American Indian and
      Alaska Native youth. However, more research on interventions to address the
      Native communities' psychosocial issues and concerns around youth-onset type 2
      diabetes is urgently needed.

PMID- 20689388
TI  - Understanding community and family barriers and supports to physical activity in
      American Indian children.

PMID- 20689387
TI  - Correlates of physical activity in young American Indian children: lessons
      learned from the Wisconsin Nutrition and Growth Study.
AB  - BACKGROUND: Obesity is a serious and growing health problem in American Indian
      (AI) children. Our study, the Wisconsin Nutrition and Growth Study, aimed to
      understand the prevalence and contributing factors to pediatric obesity in
      Wisconsin tribes and provide the foundation for intervention design. OBJECTIVE:
      This article focuses on associations among age, gender, and 3 measures of weight
      status with proxy-reported physical activity and TV/screen time in 3 to 8 year
      old AI children. DESIGN/METHODS: In a cross-sectional design, 581 AI children
      (49.1% female, aged 3-8 years) participated in health screenings that included
      height, weight, waist circumference, percent body fat, and a caregiver survey on
      demographics and health, with questions on physical activity and TV/screen time.
      RESULTS: Forty-five percent of children were overweight or obese. Boys were
      significantly more obese and had higher levels of body fat than girls. There were
      no differences in weight category across age groups. Boys participated in
      significantly more weekly sports than girls and sports participation was somewhat
      higher in younger children. Body mass index and waist circumference were not
      significantly correlated with TV/screen time or with the 3 activity measures
      (sports participation, outdoor play time, or physical education classes). Hours
      of outdoor play significantly predicted child body fat percentage controlling for
      maternal body mass index and child age and gender. CONCLUSIONS: Young AI children
      in Wisconsin have high rates of overweight/obesity starting at a very early age,
      and outdoor play may play a significant role in mediating body fat. There is a
      need to develop obesity-prevention interventions at early ages.

PMID- 20689389
TI  - Measuring physical activity: practical approaches for program evaluation in
      Native American communities.
AB  - Promoting physical activity is a high priority in the United States, especially
      for Native American populations, due to very high rates of inactivity-related
      chronic diseases. High-quality physical activity measures can contribute to
      achieving health goals. Measuring a sample of the population can identify high
      risk subgroups and geographic locations that can be targeted for interventions.
      Outcomes of physical activity interventions should be evaluated because this is
      the only way to determine whether they are effective. Three types of measures are
      practical for use in nonresearch settings, although they still present
      challenges. First, self-reports are commonly used; they are low-cost but the
      least accurate. Second, objective monitors such as pedometers, accelerometers,
      and heart rate monitors can provide accurate information, but resources and
      expertise are needed to collect and manage data. Third, direct observation can be
      used to evaluate school physical education programs and assess how people are
      using parks and other physical activity facilities. Studies of Native American
      populations have used a variety of measures. Good evaluations can lead to program
      improvements, documenting positive results can attract funding to continue and
      expand programs, and communicating results can persuade other communities to
      adopt effective approaches. Program evaluations using quality physical activity
      measures can contribute to achieving the goal of improved health in Native
      American communities.

PMID- 20689390
TI  - A latent profile analysis of neighborhood recreation environments in relation to
      adolescent physical activity, sedentary time, and obesity.
AB  - OBJECTIVEV: This study examined whether multivariate profiles of the neighborhood
      recreation environment were associated with adolescent physical activity,
      sedentary time, and obesity. DESIGN: Residential addresses of 871 adolescents in
      San Diego County (53% female, mean age = 12.8 years) were geocoded to create 1
      mile network buffers. MEASURES: Geographic information systems calculated
      neighborhood environmental variables. Accelerometers (worn 3-7 days) estimated
      daily moderate to vigorous physical activity (MVPA) and sedentary time. Height
      and weight were directly measured. RESULTS: Latent profile analysis, using 7
      environmental variables, resulted in 3 neighborhood profiles characterized as
      "open space" (OS), "residential with cul-de-sacs" (RWC), and "housing & facility
      dense" (HFD). These were named Adolescent Recreation Environment Accessibility
      (AREA) profiles. Multiple regression models stratified by gender tested
      associations between the AREA profiles and outcomes. Boys were less sedentary in
      the OS and RWC neighborhoods (7 hours per day) compared with the HFD
      neighborhoods (8 hours per day) (P < .01), and boys were more likely to be obese
      in the HFD neighborhoods (55%) compared with the OS group (24%) (P < .05). Girls
      in the RWC neighborhoods had lower MVPA levels (70 minutes per day) and were more
      likely to be obese (31%) than those in the OS neighborhoods (79 minutes per day
      MVPA, 21% obese) (Ps < .05). No differences were found for boys' MVPA or girls'
      sedentary time by the AREA profiles. CONCLUSIONS: These findings highlight the
      complex relationships among environmental factors, activity levels, and
      obesity.nn.

PMID- 20689391
TI  - Physical activity measurements: lessons learned from the pathways study.
AB  - High obesity rates in American Indian children led to Pathways, a randomized
      school- and community-based childhood prevention study. Seven tribes, 5
      universities, the National Institutes of Health/National Heart, Lung, and Blood
      Institute, and 4 elementary schools partnered in the study. Increasing physical
      activity (PA) was an important intervention target. The PA assessment was based
      on study objectives, feasibility, and tribal acceptance. A time-segmented
      analysis was also desired. Two methods, a new PA questionnaire and accelerometry,
      were developed during pilot testing. Together, the methods provided qualitative
      and quantitative information and showed that 3 of 4 sites were able to increase
      average daily PA, although overall the control versus intervention difference was
      not significant. The main limitation was inability to distinguish PA among
      individuals. Accelerometer size and some community concerns led to a protocol
      based on a single day of wearing time. Newer model triaxial accelerometers that
      are much smaller and allow sampling of multiple days of activity are recommended
      for future studies.

PMID- 20689392
TI  - Making physical activity programs work for american indian/alaska native youth at
      risk for obesity and type 2 diabetes mellitus.

PMID- 20689393
TI  - Measuring the retail food environment in rural and urban North Carolina counties.
AB  - BACKGROUND: Development of accurate and sensitive methods to characterize the
      food environment is needed. Thus, we examined convergent and criterion validity
      of 2 retail food environment data sources and then examined differences in
      predictive validity between 3 ways of measuring the rural and urban food
      environment. METHODS: Ten counties were selected in each of 3 North Carolina
      regions (n = 30). Number of fast-food restaurants and chain supermarkets were
      calculated using 2 data sources. Convergent validity was percent agreement
      between the 2 sources. Criterion validity was percent agreement between each
      source and the most accurate venue count. Predictive validity of food environment
      measures (Retail Food Environment Index, fast-food restaurants/capita, and
      supermarkets/capita) was calculated by associations with county-level mean
      weighted body mass index (BMI). RESULTS: Percent agreement for fast-food
      restaurants ranged from 50% to 100% (mean = 87%) and for supermarkets ranged from
      58% to 100% (mean = 89%). The 2 data sources had similar percent agreement with
      the most accurate count. Retail Food Environment Index was positively associated
      with BMI, while fast-food restaurants per capita were negatively associated with
      BMI. CONCLUSIONS: Our results lend support to studies using both food environment
      data sources examined.

PMID- 20689394
TI  - The nature of the public health emergency preparedness literature 2000-2008: a
      quantitative analysis.
AB  - OBJECTIVES: This study characterizes the nature, size, and knowledge gaps of the
      public health emergency preparedness (PHEP) literature. METHODS: Systematic
      review of PHEP articles published in 10 relevant journals from 2000 through 2008
      was conducted. An inclusion process and coding sheet was developed; articles were
      coded on the basis of abstract content for variables, including type of methods
      used, disaster type, disaster life cycle focus, and article focal point.
      Descriptive analyses and cross-tabulations were used to characterize the nature
      of the literature. RESULTS: The sample included 823 articles; human-made
      disasters (39.4%, n = 323) were the most common, followed by natural disasters
      (30.7%, n = 252). The preparedness life cycle phase represented 60.5% (n = 497)
      of articles. Overall, 67.8% (n = 558) of articles were nonempirical; however,
      this differed by disaster type and focal point. DISCUSSION: Most of the PHEP
      literature is based on commentaries and other nonempirical articles forcing
      policymakers and practitioners to rely on weak anecdotal evidence or opinions for
      decision making. Several literature gaps are identified and presented as areas
      for future research. More research utilizing diverse methods and data sets is
      needed to build a strong evidence-based knowledge base on many PHEP topics.

PMID- 20689395
TI  - Physician and nurse perspectives on implementation of universal adult HIV
      screening guidelines in the Indian health service: results of a randomized
      survey.
AB  - OBJECTIVES: We sought to determine attitudes and needs among health care
      providers in the Indian Health Service toward implementing routine human
      immunodeficiency virus (HIV) screening among 13- to 64-year-olds as per Centers
      for Disease Control and Prevention (CDC) guidelines. METHODS: We surveyed a
      random sample of Indian Health Service physicians and nurses by e-mail and
      telephone interview. A total of 205 eligible respondents (response rate = 70%)
      completed the survey. RESULTS: A majority (58%) of respondents were familiar or
      somewhat familiar with the 2006 CDC guidelines on HIV screening for 13- to 64
      year-olds. A proportion of respondents (43%) felt that community HIV prevalence
      was below the 0.1% threshold the CDC recommends to initiate screening.
      Respondents supported routine, rather than solely risk-based HIV testing (70%)
      and stated that HIV screening would be realistic in their health facility (51%).
      Respondents felt that they needed special qualification to offer an HIV test
      (49%) or to notify a patient of a "reactive" HIV test result (67%). CONCLUSIONS:
      A majority of Indian Health Service physicians and nurses support the CDC HIV
      screening guidelines. Providers need more information and training on HIV
      screening guidelines, implementation strategies, and relevant state HIV
      regulations.

PMID- 20689396
TI  - Cost-effectiveness of using social networks to identify undiagnosed HIV infection
      among minority populations.
AB  - CONTEXT: In 2003, the Centers for Disease Control and Prevention launched the
      Advancing HIV Prevention project to implement new strategies for diagnosing human
      immunodeficiency virus (HIV) infections outside medical settings and prevent new
      infections by working with HIV-infected persons and their partners. OBJECTIVES: :
      To assess the cost and effectiveness of a social network strategy to identify new
      HIV diagnoses among minority populations. DESIGN, SETTINGS, AND PARTICIPANTS:
      Four community-based organizations (CBOs) in Boston, Philadelphia, and
      Washington, District of Columbia, implemented a social network strategy for HIV
      counseling and testing from October 2003 to December 2005. We used standardized
      cost collection forms to collect program costs attributable to staff time,
      travel, incentives, test kits, testing supplies, office space, equipment, and
      utilities. The CBOs used the networks of high-risk and HIV-infected persons
      (recruiters) who referred their partners and associates for HIV counseling and
      testing. We obtained HIV-testing outcomes from project databases. MAIN OUTCOME
      MEASURES: Number of HIV tests, number of new HIV-diagnoses notified, total
      program cost, cost per person tested, cost per person notified of new HIV
      diagnosis. RESULTS: Two CBOs, both based in Philadelphia, identified 25 and 17
      recruiters on average annually and tested 136 and 330 network associates,
      respectively. Among those tested, 12 and 13 associates were notified of new HIV
      diagnoses (seropositivity: 9.8%, 4.4%). CBOs in Boston, Massachusetts, and
      Washington, District of Columbia, identified 26 and 24 recruiters per year on
      average and tested 228 and 123 network associates. Among those tested, 12 and 11
      associates were notified of new HIV diagnoses (seropositivity: 5.1%, 8.7%). The
      cost per associate notified of a new HIV diagnosis was $11 578 and $12 135 in
      Philadelphia, and $16 437 and $16 101 in Boston, Massachusetts, and Washington,
      District of Columbia. CONCLUSIONS: The cost of notifying someone with a new HIV
      diagnosis using social networks varied across sites. Our analysis provides useful
      information for program planning and evaluation.

PMID- 20689397
TI  - Public health workforce training: application of the Council on Linkages' core
      competencies.
AB  - Despite calls from multiple sources, including the Institute of Medicine, a large
      proportion of public health professionals have limited formal training in public
      health science. The Council on Linkages Between Academia and Public Health
      Practice developed the core competencies to provide a framework for assessing
      professionals' readiness to manage the complex challenges in public health. We
      incorporated the core competencies into a workforce development program to
      improve workforce competence of professionals at the Arkansas Department of
      Health. The program's curriculum was mapped to the core competencies in each of
      the Linkages domains. Participants self-assessed their competence before and
      after the year-long program, and results from the 2007 and 2008 participants are
      provided. The 2007 results indicate that participants significantly increased
      their perceived competence in all of the Linkages domains, whereas in the 2008
      program, participants reported increases in all but cultural competency. The
      greatest reported increase in perceived competency was in policy development. On
      the basis of these findings, the Council on Linkages core competencies appear to
      be an effective tool in guiding workforce development programs and serve as an
      important framework for assessing comprehensive interdisciplinary training
      programs. Such programs can substantially increase public health professionals'
      self-assessed competence in the Linkages domains.

PMID- 20689398
TI  - Practicing management and leadership: vision, strategy, operations, and tactics.

PMID- 20689399
TI  - NACCHO resources help local health departments fight obesity.

PMID- 20689400
TI  - Clear-cell change and diabetes.

PMID- 20689401
TI  - All that glitters is not pemphigus: Pyodermatitis-pyostomatitis vegetans
      misdiagnosed as IgA pemphigus for 8 years.
AB  - Pyodermatitis-pyostomatitis vegetans is a rare mucocutaneous dermatosis often
      associated with gastrointestinal disorders, especially with inflammatory bowel
      disease. It is clinically characterized by erythematous lesions with multiple
      pustules and erosions affecting the mucosal surfaces. Cutaneous lesions are
      characterized by exudative and vegetating plaques affecting frequently the
      axillae and groins. The clinical diagnosis is supported by histologic findings,
      whereas immunofluorescence studies are useful to rule out other entities such as
      pemphigus3. Herein we report the case of a young man who was misdiagnosed as
      having IgA pemphigus for 8 years due to positive immunofluorescence findings. The
      clue for the final diagnosis was the diagnosis of a concomitant ulcerative
      colitis, which prompted us to reconsider his cutaneous disease.

PMID- 20689402
TI  - Coagulation abnormalities following thermal injury.
AB  - Changes in coagulation may have a profound impact on outcomes following severe
      burns and the coagulation abnormalities after thermal injury are incompletely
      described. We postulated that thermal injury induces a systemic hypercoagulable
      state. With Institutional Review Board approval, five patients were consented for
      enrollment in this case series. After obtaining informed consent, blood was drawn
      on hospital days 1, 2, 3, 5, and 7 or until discharge if discharge was in less
      than 7 days. Standard coagulation testing was performed, as well as a battery of
      sophisticated specialized coagulation assays. Other data collected includes fluid
      resuscitation volumes, pharmacologic interventions, and general physiologic
      information. Results (n = 5) demonstrate that burns less than 6% total body
      surface area appear to have little effect on coagulation. Burns greater than 6%
      appear to induce a systemic hypercoagulable state with a phase and magnitude
      relationship proportional to total body surface area burned. Severe burns greater
      than 40% appear to induce a consumptive coagulopathy. Prothrombin fragment 1.2
      may represent a useful screening test for a burn-induced hypercoagulable state.

PMID- 20689403
TI  - Effects of different doses, enteric-coated preparation of aspirin, and sex on
      urinary 11-dehydrothromboxane B2 in healthy volunteers.
AB  - There is scarce information about the effects of different doses and enteric
      coated preparation of aspirin on platelet function, especially in Asian people,
      evaluated by the measurement of urinary 11-dehydrothromboxane B2 (dTXB2). The
      objective of the present study was to assess the effects of different doses,
      enteric-coated preparation of aspirin, sex and also the effects of timing of
      urine collection on urinary dTXB2 level in healthy volunteers. Thirty healthy
      volunteers were included. Each volunteer took three preparations of aspirin
      (aspirin 81 mg, enteric-coated aspirin 300 mg and aspirin 300 mg) for 7 days.
      Urine dTXB2 level was measured at baseline, day 3, and day 7 after taking each
      preparation of aspirin. There was no significant difference in the effects of
      different doses of aspirin (81 vs. 300 mg, 50.7 vs. 61.8 ng/mmol creatinine, P =
      0.248), preparations (enteric-coated vs. nonenteric-coated aspirin, 61.8 vs. 67.9
      ng/mmol creatinine, P = 0.527) and time of urine collection (day 3 vs. day 7,
      51.7 vs. 49.9 ng/mmol creatinine, P = 0.448). Female volunteers showed a trend to
      have higher urinary dTXB2 than male volunteers at baseline and after taking
      aspirin. This study showed no significant difference in urinary dTXB2 level after
      taking different doses and enteric-coated preparation of aspirin in healthy
      volunteers.

PMID- 20689404
TI  - Minimal dose for severe poisoning and influencing factors in acute human
      clozapine intoxication: a 13-year retrospective study.
AB  - OBJECTIVES: Clozapine is an atypical antipsychotic drug used in the treatment of
      resistant schizophrenia. Intoxications with this drug are frequently observed.
      The aim of the present study was to identify a minimal dose and the dose bearing
      a 50% risk of developing moderate or severe intoxication symptoms. We also
      investigated the influence of age, sex, effect of decontamination measures, and
      pretreatment with clozapine on the severity of poisoning. METHODS: A
      retrospective case study of 73 acute clozapine monointoxications reported by
      physicians to the Swiss Toxicological Information Centre between 1995 and 2007.
      RESULTS: The most common symptoms were central nervous system depression (63.1%),
      tachycardia (39.7%), restlessness/agitation (16.4%), confusion/disorientation
      (15.1%), dysarthria (15.1%), arterial hypertension (10.9%), bradykinesia (9.6%),
      respiratory depression (9.6%), and QTc prolongation (8.2%). We found a
      significant correlation between ingested clozapine dose and severity of
      poisoning. The minimal dose for both moderate and severe intoxications was 0.1 g.
      The dose for a 50% risk of developing moderate or severe intoxications was 0.9 g
      in patients older than 50 years and 14.5 g in patients younger than 50 years.
      Patients older than 50 years had a significantly increased risk for a severe
      clinical course (odds ratio, 6.41; 95% confidence interval, 1.88-21.90). We found
      no significant correlation between pretreatment, sex or decontamination, and the
      severity of the intoxication. CONCLUSIONS: Moderate and severe clozapine
      intoxications can already occur after ingestion of doses in the low therapeutic
      range, especially in patients older than 50 years. Poisoned patients have to be
      monitored for central nervous system depression, tachycardia, blood pressure
      abnormalities, respiratory depression, and QTc prolongation.

PMID- 20689405
TI  - Keratinocytes in allergic skin diseases.
AB  - PURPOSE OF REVIEW: The aim of the review is to provide up-to-date information on
      the multiple roles of epidermal keratinocytes in the immune reactions associated
      with allergic contact dermatitis and atopic dermatitis skin diseases. RECENT
      FINDINGS: In the last two decades, it has become clear that keratinocytes are
      highly active immunological cells, with major control over the acute and the
      chronic phases of skin inflammation by means of cytokine/chemokine production and
      surface molecule expression. Keratinocyte responses in skin allergic reactions
      are rather disease-specific and keratinocytes from genetically determined skin
      disorders, including atopic dermatitis, show intrinsic abnormalities in their
      capacity to respond to trigger factors. SUMMARY: Lymphokines and cytokines
      released by T lymphocytes and other immune cells represent the most important
      stimuli that elicit the inflammatory activation of keratinocytes. Depending on
      the type and extent of T-cell infiltrate present in allergic contact dermatitis
      and atopic dermatitis skin lesions, keratinocytes are exposed to different
      cytokine micromilieu and, in turn, produce flogosis mediators qualitatively and
      quantitatively specific for each disease. Keratinocyte-derived inflammatory
      molecules amplificate skin immune responses associated with allergic contact
      dermatitis and atopic dermatitis, and contribute to the disease process and
      clinical phenotype development.

PMID- 20689406
TI  - High-risk corneal allografts and why they lose their immune privilege.
AB  - PURPOSE OF REVIEW: Corneal allografts are routinely performed without HLA typing
      or systemic immunosuppressive drugs. However, certain conditions create high
      risks for immune rejection. This review discusses recent insights into the
      mechanisms that rob the corneal allograft of its immune privilege. RECENT
      FINDINGS: Studies in mice have revealed that stimuli that induce new blood vessel
      growth in the cornea also elicit proliferation of lymph vessels. Lymph vessels
      facilitate migration of antigen-presenting cells to regional lymph nodes in which
      they induce alloimmune responses. The presence of blood vessels in the corneal
      graft bed creates a unique chemokine milieu that stimulates recruitment of
      sensitized lymphocytes into the corneal allograft. Other data indicate that
      although corneal allograft survival is closely associated with Foxp3 expression
      in CD4+CD25+Foxp3+ T regulatory cells (Tregs), reduced expression of Foxp3 in
      Tregs creates a high risk for graft rejection. Recent evidence indicates that
      allergic diseases have a profound impact on the immune response and produce a
      dramatic increase in corneal allograft rejection. SUMMARY: Understanding the
      underlying mechanisms that create 'high-risk' hosts may provide important
      therapeutic targets for restoring immune privilege of corneal allografts and
      enhancing their survival.

PMID- 20689407
TI  - Pathogenic role of Demodex mites in blepharitis.
AB  - PURPOSE OF REVIEW: To summarize the key literature and our research experience
      regarding Demodex infestation as a potential cause of ocular inflammatory
      diseases with a special emphasis on Demodex blepharitis. RECENT FINDINGS: Two
      distinct Demodex species have been confirmed as a cause of blepharitis: Demodex
      folliculorum can cause anterior blepharitis associated with disorders of
      eyelashes, and D. brevis can cause posterior blepharitis with meibomian gland
      dysfunction and keratoconjunctivitis. Tea tree oil treatments with either 50% lid
      scrubs or 5% lid massages are effective in eradicating mites and reducing ocular
      surface inflammation. SUMMARY: Demodex blepharitis is a common but overlooked
      external eye disease. The pathogenesis of Demodex blepharitis in eliciting ocular
      surface inflammation has been further clarified. The modified eyelash sampling
      and counting method makes it easier and more accurate to diagnose Demodex
      infestation. Tea tree oil shows promising potential to treat Demodex blepharitis
      by reducing Demodex counts with additional antibacterial, antifungal, and anti
      inflammatory actions.

PMID- 20689408
TI  - Current concepts and future trends in ultrasound-guided regional anesthesia.
AB  - PURPOSE OF REVIEW: Ultrasound guidance for regional anesthesia has gained
      enormous popularity during the past several years. This review article highlights
      the importance of acquiring an understanding and knowledge of human anatomy for
      well tolerated and effective performance of regional anesthesia; includes
      description of some of the major principles of ultrasound-guided regional
      anesthesia techniques (adequate identification of neuronal and adjacent
      anatomical structures along with the procedure needle); use of adequate volumes
      of local anesthetic and the proper administration of local anesthetic; and
      discusses economical along with educational aspects of ultrasound-guided regional
      blocks. RECENT FINDINGS: Recent studies by various authors have indicated that
      ultrasound-guided regional blocks can be performed by using smaller volumes of
      local anesthetics. Such findings will further contribute to the safety of
      regional anesthesia in daily clinical practice. Additional positive economical
      aspects associated with regional anesthesia have also been described in the
      recent literature. SUMMARY: With little reservation, it is anticipated that
      ultrasound-guided regional anesthesia will become the 'GOLD' standard for
      performance of regional anesthesia. Excellent science and educational concepts
      will continue to be required with the continued increase in popularity of this
      exciting specialty of anesthesia.

PMID- 20689409
TI  - Is nitrous oxide use appropriate in neurosurgical and neurologically at-risk
      patients?
AB  - PURPOSE OF REVIEW: To address controversial issues surrounding the use of nitrous
      oxide as a component of anesthesia in neurosurgical and neurologically at-risk
      patients. RECENT FINDINGS: Nitrous oxide has been used as a component of general
      anesthesia for over 160 years and has contributed to countless apparently
      uneventful anesthetics in neurologically at-risk patients. Avoidance of nitrous
      oxide in specific circumstances, such as pre-existing pneumocephalus, during
      acute venous air embolism, and in patients with disorders of folate metabolism,
      is warranted. However, various controversies exist regarding the use of this drug
      in the general neurosurgical population. Specifically, some suggest a possible
      association between nitrous oxide and the postoperative development of tension
      pneumocephalus despite lack of data to support this notion. Additionally, data
      describing alterations of cerebral hemodynamics and metabolism and exacerbation
      of ischemic neurologic injury by nitrous oxide are inconsistent. Recent data
      derived from humans having cerebral aneurysm clipping failed to show any long
      term adverse effect from the use of nitrous oxide on gross neurologic or
      cognitive function. SUMMARY: Except in a few specific circumstances, there exists
      no conclusive evidence to support the dogmatic avoidance of nitrous oxide in
      neurosurgical patients.

PMID- 20689410
TI  - Glucose management in the neurosurgical patient: are we yet any closer?
AB  - PURPOSE OF REVIEW: This review focuses on recent findings in perioperative
      management of blood glucose control using intensive insulin therapy in
      neurosurgical and neurocritical care and in other intensive care unit patients.
      We also aim to address practical issues and make recommendations that may
      contribute to the safe clinical application of intensive insulin therapy targeted
      to optimize blood glucose control in these patients. RECENT FINDINGS: Intensive
      insulin therapy targeted to obtain tight blood glucose control induces a
      substantial increase in the number of hypoglycemic episodes and mortality rate.
      On the contrary, hyperglycemia--both isolated episodes and high mean glucose
      levels--is associated with worsened neurologic outcome and increased mortality.
      SUMMARY: In neurosurgical and neurocritical care as well as other intensive care
      unit patients, both hypoglycemia and hyperglycemia have significant adverse
      effects. The optimal glucose level remains under debate but significant steps
      have evolved with the call for judicious control and elimination of the
      historical approach to glycemic management, which underestimated drawbacks
      associated with dysglycemia. The increased incidence of hypoglycemia and
      mortality as well as the impact of hyperglycemia on worsening neurologic function
      in patients with acute brain damage heightens the need for more clinical studies
      on perioperative glucose management in these patients.

PMID- 20689411
TI  - Antiepileptic drug therapy in the perioperative course of neurosurgical patients.
AB  - PURPOSE OF REVIEW: Antiepileptic agents are widely used in the perioperative
      course of neurosurgical patients - for prophylactic and therapeutic reasons.
      However, the evidence supporting their use is extremely small and adverse events
      are common. This review highlights the current controversies. RECENT FINDINGS:
      Prophylactic use of antiepileptic agents is unfavorable for patients with
      subarachnoid hemorrhage. In patients with brain tumors, prophylactic use is not
      recommended. If the drugs are used nevertheless, stopping after the first
      postoperative week must be strongly recommended. After traumatic brain injury,
      early prophylactic use might prevent late post-traumatic seizures. The new
      antiepileptic drug levetiracetam seems to have a better safety profile, which
      makes it more suitable for prophylactic use. However, in all groups, evidence
      concerning the choice of drugs and duration of prophylaxis is lacking. Current
      research is focusing on prevention of epileptogenesis. Therapeutic use of
      antiepileptic drugs is supported by evidence. These drugs should be continued
      perioperatively. However, they might induce severe adverse events during adjuvant
      treatments like radiotherapy or chemotherapy in patients with brain tumors.
      SUMMARY: Despite lacking evidence, prophylactic antiepileptic drug use is common
      in the perioperative course of neurosurgical patients. More research is needed to
      deal better with epileptogenesis and to define the right drug for the right
      patient at the right time.

PMID- 20689412
TI  - From basic concepts to emerging technologies in regional anesthesia.
AB  - PURPOSE OF REVIEW: The present article details how our understanding of the basic
      concepts of regional anesthesia has recently evolved. We will appraise current
      technological advances and question the commensurate nature of the relationship
      between tradition and innovation. RECENT FINDINGS: Ultrasound localization has
      enhanced our understanding of the needle-nerve relationship. Intraneural
      injection of local anesthetic may occur with greater frequency than previously
      thought without inevitably leading to neurological complications. The ratio of
      neural to non-neural tissue varies both between and within nerves and may be an
      important determinant of neural injury. Ultrasonographic evidence of intraneural
      injection is subject to observer expertise and the resolution of the ultrasound
      image. Current ultrasound resolution capability does not reliably permit
      differentiation between intrafascicular and extrafascicular drug injection.
      Perineural electrical impedance may be a determinant of current threshold and
      conceivably distinguish between intraneural and extraneural tissue. Technology
      that enhances the sonographic image of both procedure needle and target nerve is
      the focus of current endeavors in ultrasound innovation.There is inconclusive
      evidence that the use of ultrasound technology has reduced the incidence of local
      anesthetic toxicity. Lipid emulsion therapy is now an accepted treatment for
      systemic local anesthetic toxicity. There are new reports on the development of
      an ultra long-acting local anesthetic agent that would permit lower doses and
      superannuate catheter-based continuous regional anesthesia techniques. SUMMARY:
      Over the past decade, our understanding of the fundamental concepts of regional
      anesthesia continues to be challenged by emerging experimental and clinical
      evidence.

PMID- 20689413
TI  - Monitoring during peripheral nerve blockade.
AB  - PURPOSE OF REVIEW: Objective monitors to warn against adverse events specific to
      the performance of nerve blockade are relatively unsophisticated compared with
      monitors used during general anesthesia. The purpose of this review is to outline
      the various monitors available, and how they can be used to reduce nerve block
      related complications. RECENT FINDINGS: Evidence is accumulating for three
      objective means of preventing complications. Electrical nerve stimulation is
      insensitive, but specific, at detecting intraneural needle placement, such that
      if a motor response is obtained with a current of 0.2 mA or less, the needle tip
      is positioned intraneurally. Ultrasonography allows for reduction of the volume
      of local anesthetic required to accomplish a nerve block, reducing the potential
      for systemic toxicity. The value of ultrasound in reducing inadvertent puncture
      of neighboring structures, while intuitive, is less clear. Finally, injection
      pressure monitoring helps objectively distinguish between an injection into low
      versus high compliance tissue (e.g. intrafascicular versus extrafascicular).
      SUMMARY: Peripheral nerve blockade has evolved from an entirely blind procedure
      to a more reproducible subspecialty. Several monitors exist to objectively guide
      and monitor needle placement and application of local anesthetics. Because these
      monitors are complementary, best practice may involve combining all of these
      monitoring options when performing peripheral nerve blocks.

PMID- 20689414
TI  - Adipocyte-myocyte crosstalk in skeletal muscle insulin resistance; is there a
      role for thyroid hormone?
AB  - PURPOSE OF REVIEW: To review original research studies and reviews that present
      data on adipocyte-myocyte crosstalk in the development of skeletal muscle insulin
      resistance with a specific focus on thyroid hormone. RECENT FINDINGS: Adipose
      tissue communicates with skeletal muscle not only through free fatty acids but
      also through secretion of various products called adipokines. Adipokines came out
      as governors of insulin sensitivity and are deregulated in obesity. In addition
      to well known leptin, adiponectin, interleukin-6 and tumor necrosis factor-alpha,
      newer adipokines like retinol-binding protein 4 have been associated with insulin
      resistance. There is mounting evidence that not only adipose tissue but also
      skeletal muscle produces and secretes biologically active proteins or 'myokines'
      that facilitate metabolic crosstalk between organ systems. In recent years,
      increased expression of myostatin, a secreted anabolic inhibitor of muscle growth
      and development, has been associated with obesity and insulin resistance. Both
      hypothyroidism and hyperthyroidism affect insulin sensitivity in multiple ways
      that might overlap adipocyte-myocyte crosstalk. Recent studies have provided new
      insights in effects of processing of the parent hormone T4 to the active T3 at
      the level of the skeletal muscle. SUMMARY: Adipocyte-myocyte crosstalk is an
      important modulator in the development of skeletal muscle insulin resistance.
      Thyroid disorders are very common and may have detrimental effects on skeletal
      muscle insulin resistance, potentially by interacting with adipocyte-myocyte
      crosstalk.

PMID- 20689415
TI  - Vitamin C requirement in surgical patients.
AB  - PURPOSE OF REVIEW: To summarize recent findings on vitamin C status and assess
      the requirement and optimal dose of supplementation in surgical patients. RECENT
      FINDINGS: Blood vitamin C concentration falls after uncomplicated surgery and
      further decreases in surgical intensive care unit patients. The decline may be
      owing to increased demand caused by increased oxidative stress. To normalize
      plasma vitamin C concentration, much higher doses than the recommended daily
      allowance or doses recommended in parenteral nutrition guidelines are needed in
      these patients. In uncomplicated surgical patients, more than 500 mg/day of
      vitamin C may be required, with much higher doses in surgical intensive care unit
      patients. In uncomplicated gastrointestinal surgery, continuous parenteral
      administration of 500 mg/day of vitamin C reduced postoperative oxidative stress
      as manifested by reduced urinary excretion of isoprostane. In some studies,
      postoperative atrial fibrillation was prevented after cardiac surgery by
      perioperative vitamin C supplementation. In critically ill patients, some
      prospective randomized controlled trials support parenteral supplementation of
      high doses of vitamin C, E and trace elements. SUMMARY: Vitamin C requirement is
      increased in surgical patients, and the potential advantage of supplementation is
      to increase the plasma and tissue levels of vitamin C and thereby reduce
      oxidative stress. Although some clinical benefits of high-dose vitamin C
      supplementation have been shown in the critically ill, the optimal dose for
      supplementation and the clinical benefits remain to be investigated in surgical
      patients.

PMID- 20689416
TI  - Role of zinc in the development and treatment of mood disorders.
AB  - PURPOSE OF REVIEW: The present review is a critical examination of the most
      recent published work on the role of zinc in the development and treatment of
      mood disorders. RECENT FINDINGS: Clinical studies and experimental work using
      animal models have both revealed a link between zinc status and
      neuropsychological disorders such as depression and anxiety. Not only has zinc
      deficiency been shown to induce depression-like and anxiety-like behaviors,
      supplementation has been used as a treatment for major depression. Zinc
      administration improves the efficacy of antidepressant drugs in depressed
      patients and may have a particular role to play in treatment-resistant patients.
      Recent investigations into the molecular mechanisms responsible for these
      observations suggest a role for zinc in the regulation of neurotransmitter
      systems, antioxidant mechanisms, neurotrophic factors, and neuronal precursor
      cells. SUMMARY: The data reviewed here not only indicate a role for zinc
      deficiency in the development of mood disorders, but also show that zinc may also
      be important in their treatment. Given the prevalence of zinc deficiency in human
      populations, this work has the potential to influence strategies to prevent and
      treat these disorders.

PMID- 20689417
TI  - Cardiovascular complications of AIDS.
AB  - PURPOSE OF REVIEW: The purpose of the present review article is to present the
      recent data on the cardiovascular complications in patients infected with HIV as
      well as the preventive strategies to reduce cardiovascular disease in those
      patients. RECENT FINDINGS: Individuals infected with HIV frequently demonstrate a
      metabolic syndrome associated with atherosclerosis and cardiovascular disease.
      Extensive functional and structural arterial wall changes have been observed in
      these individuals. It is documented that these vascular changes are closely
      related to highly active antiretroviral treatment-induced metabolic disorders as
      well as characteristics of the HIV infection itself. Intensive treatment of
      vascular dysfunction might be helpful in preventing or retarding the
      atherosclerotic process in HIV patients. SUMMARY: Marked changes in arterial
      function and structure are observed in HIV patients leading to increased
      cardiovascular morbidity and mortality. Early antiretroviral therapy and
      aggressive treatment of cardiovascular risk factors might be helpful.

PMID- 20689418
TI  - Critical care: the impact of organization and management on outcomes.
AB  - PURPOSE OF REVIEW: The organization and management of ICUs are key components
      that can affect delivery and outcome of critical care. RECENT FINDINGS: At the
      healthcare system level, the provision of critical care services and the presence
      of a regionalized system of critical care delivery may improve optimal matching
      of patient severity with level of care and is associated with improved patient
      outcomes. In hospitals, rapid response teams and step-down beds affect admission
      and discharge criteria to and from the ICU, although the influence on outcome is
      unclear. And within the ICU, the presence of intensivists, physically or via
      telemedicine, and multidisciplinary teams may promote better use of therapeutic
      and preventive measures with improved patient outcomes. Recent findings also
      emphasize that strategies that promote teamwork and communication, standardize
      processes of care, emphasize engagement in quality improvement, and provide a
      positive safety culture are associated with improved patient outcomes and staff
      morale. SUMMARY: Evidence suggests the implementation of some ICU organizational
      and managerial patterns are associated with improved patient and staff outcomes.
      Broader adoption of some of these strategies could, therefore, improve overall
      critical care delivery.

PMID- 20689419
TI  - Obesogens.
AB  - PURPOSE OF REVIEW: The environmental obesogen hypothesis postulates chemical
      pollutants that are able to promote obesity by altering homeostatic metabolic set
      points, disrupting appetite controls, perturbing lipid homeostasis to promote
      adipocyte hypertrophy, or stimulating adipogenic pathways that enhance adipocyte
      hyperplasia during development or in adults. This review focuses on recent
      experimental advances for candidate obesogens that target nuclear hormone
      receptors when a direct link between exposure, modulation of transcriptional
      networks and adipogenic phenotypes can be rationalized. RECENT FINDINGS: Various
      endocrine disrupting chemicals can disrupt hormonal signaling relevant to adipose
      tissue biology. In this review, progress on one identified obesogen, the
      organotin tributyltin, will be outlined to highlight principles and novel
      insights into its high-affinity nuclear hormone receptor-mediated mechanism, its
      effects on adipocyte biology, its potential to promote long-term obesogenic
      changes and its epidemiological relevance. When appropriate, important results
      for other suspected obesogenic ligands, including bisphenol A, phthalates,
      polybrominated diphenyl ethers and perfluoro-compounds, will highlight
      corroborating principles. SUMMARY: These examples serve to provide perspective on
      the potential harm that man-made obesogenic pollutants pose to human health,
      focus attention on areas in which knowledge remains inadequate and prompt a re
      evaluation of the causative risk factors driving the current changes in obesity
      rates.

PMID- 20689420
TI  - Thyroid hormones and cancer: clinical studies of hypothyroidism in oncology.
AB  - PURPOSE OF REVIEW: To collect and assess clinical reports of a putative
      relationship between thyroid state and the biology of cancers of various types.
      RECENT FINDINGS: A number of prospective case-control studies reviewed here have
      suggested that subclinical hyperthyroidism increases risk of certain solid tumors
      and that spontaneous hypothyroidism may delay onset or reduce aggressiveness of
      cancers. Small case studies have reached similar conclusions. A controlled
      prospective trial of induced hypothyroidism beneficially affected the course of
      glioblastoma. A context in which to interpret such findings is the recent
      description of a plasma membrane receptor for thyroid hormone on cancer cells and
      dividing tumor-associated endothelial cells. SUMMARY: Accumulating clinical
      evidence may justify new, broadly-based controlled studies in cancer patients of
      the possible contribution of thyroid hormone to tumor behavior.

PMID- 20689421
TI  - Social influence and obesity.
AB  - PURPOSE OF REVIEW: To review a selection of research published in the last 12
      months on the role of social influence in the obesity epidemic. RECENT FINDINGS:
      Recent papers add evidence to previous work linking social network structures and
      obesity. Social norms, both eating norms and body image norms, are identified as
      one major source of social influence through networks. Social capital and social
      stress are additional types of social influence. SUMMARY: There is increasing
      evidence that social influence and social network structures are significant
      factors in obesity. Deeper understanding of the mechanisms of action and dynamics
      of social influence, and its link with other factors involved in the obesity
      epidemic, is an important goal for further research.

PMID- 20689422
TI  - Treatment of cryptosporidiosis: do we know what we think we know?
AB  - PURPOSE OF REVIEW: The management of cryptosporidiosis is fraught with
      controversies. New research on diagnostics and medications has reached the field
      in recent years. Therefore, familiarity with key features of current management
      tools is important. We discuss diagnostic and therapeutic aspects of
      cryptosporidiosis focusing on evidence behind the medications available to date.
      RECENT FINDINGS: Molecular methods provide a clearer understanding of
      cryptosporidiosis epidemiology. The major determinants of severity still are host
      immune status and parasite species. Children and immunosuppressed individuals,
      especially with HIV/AIDS, are disproportionately affected. Nitazoxanide is an
      important advance in treatment of HIV negative patients. However, recent research
      confirms the limited effectiveness of antiparasitic drugs to treat
      cryptosporidiosis in AIDS. Questions remain about using partially active drugs
      paromomycin and nitazoxanide for treatment. Potent antiretroviral combinations
      modify disease epidemiology and are key components of therapy in AIDS. However,
      it is unclear whether this is due solely to immune reconstitution or due in part
      to antiparasitic effects of HIV protease inhibitors. Newer candidate drugs are in
      development. SUMMARY: There is better understanding of the epidemiology of
      cryptosporidiosis and promising new diagnostic methods. There are significant
      challenges in terms of control and treatment of cryptosporidiosis among the
      groups at risk.

PMID- 20689423
TI  - Shigellosis update: advancing antibiotic resistance, investment empowered vaccine
      development, and green bananas.
AB  - PURPOSE OF REVIEW: Shigella is the principal cause of clinical dysentery and an
      important cause of morbidity and mortality among children in impoverished
      regions. The purpose of this review is to present key findings in the areas of
      epidemiology, disease control, and treatment of shigellosis. RECENT FINDINGS:
      Recent research activity has advanced the understanding of the epidemiology and
      host-pathogen interactions. Increased investment and activity in the area of
      vaccine development have lead to a diversification of candidates and ongoing
      technical advances yet continue to yield disappointing results in clinical trials
      in endemic populations and among the most relevant age groups (children under 2
      years of age). The description of the rapid spread of quinolone resistance
      requires monitoring to ensure appropriate case management, particularly in south
      east Asia. The evaluation of adjunctive nutritional therapy in endemic areas has
      supported the use of green bananas in shortening the duration of Shigella
      dysentery and persistent diarrhea due to Shigella, as well as improving weight
      gain in early convalescence. SUMMARY: Despite a great level of activity in basic
      sciences, there continues to be a large gap in the ability to translate these
      findings into disease control measures or therapeutic options for individuals
      living in areas in which shigellosis is endemic.

PMID- 20689424
TI  - Vasopressin beyond water: implications for renal diseases.
AB  - PURPOSE OF REVIEW: This review aims to analyze the relationships between arginine
      vasopressin (AVP) and chronic kidney disease (CKD) and to define the potential of
      vasopressin receptor antagonists beyond the treatment of water metabolism
      disorders. RECENT FINDINGS: Experimental studies in rat and observational studies
      in humans suggest that AVP may play a role in the genesis and exacerbation of
      renal damage and chronic renal insufficiency. SUMMARY: A sustained stimulation of
      vasopressin receptors induces intrarenal renin-angiotensin system activation,
      podocyte alterations, glomerular hyperfiltration and hypertrophy eventuating in
      proteinuria and kidney damage. Furthermore, AVP directly stimulates contraction
      and proliferation of mesangial cells and accumulation of extracellular matrix and
      glomerulosclerosis. Whether a chronic increase in water intake (determining a
      reduction in endogenous AVP levels) and/or the administration of vasopressin
      receptor antagonists are useful for the prevention and treatment of CKD remains
      to be tested in clinical trials.

PMID- 20689425
TI  - What is causing the mortality in treating the anemia of chronic kidney disease:
      erythropoietin dose or hemoglobin level?
AB  - PURPOSE OF REVIEW: This article examines the potential mechanisms underlying
      adverse risk observed in four randomized controlled trials of anemia correction
      in chronic kidney disease (CKD) patients. RECENT FINDINGS: The Normal Hematocrit
      Study, Cardiovascular Risk Reduction by Early Anemia Treatment with Epoetin-beta,
      Correction of Hemoglobin and Outcomes in Renal Insufficiency, and Trial to Reduce
      Cardiovascular Events with Aranesp Therapy demonstrate increased risk of
      mortality and/or cardiovascular complications with targeting of a higher
      hemoglobin (Hb) in CKD patients. Although a higher Hb level was targeted in these
      trials, erythropoiesis-stimulating agent (ESA) exposure itself might account for
      the observed increased risk. This is because, in these trials, achieving a normal
      or near normal Hb was associated with improved survival and reduced
      cardiovascular risk. Indeed, it was the 'targeting' of a higher Hb with ESA that
      seemed to be the problem. Observational data, although conflicting, on the whole
      provide support for high dosage of ESA being harmful but cannot, by their very
      nature, prove causality. SUMMARY: After 20 years of ESA use, is it plausible that
      ESAs could be toxic? How does one reconcile conflicting observational data with a
      hypothesis that postulates ESA toxicity? Does the biology of erythropoietin
      provide a mechanistic explanation? The answers to these questions, among others,
      will be important in charting a future role for ESAs in treating CKD anemia.

PMID- 20689426
TI  - Neurological manifestations of primary Sjogren's syndrome.
AB  - PURPOSE OF REVIEW: This review summarizes our current understanding of the
      neurological manifestations of primary Sjogren's syndrome (PSS), their
      pathophysiology, and treatment. RECENT FINDINGS: Prevalence of neurological
      manifestations in PSS varies widely from 10 to 60%, with pure or predominantly
      sensory polyneuropathies as the most common neurologic manifestation (e.g.
      sensory ataxic or small fiber sensory painful neuropathy). Mononeuropathy
      multiplex, polyradiculopathy, symptomatic dysautonomia, cranial neuropathy,
      myopathy, and central nervous system involvement are less common. PSS-associated
      sensory neuropathy is often the presenting feature of Sjogren's syndrome and,
      therefore, a high index of suspicion is required, particularly in female patients
      with nonlength-dependent, painful, or ataxic sensory neuropathies or those with
      trigeminal sensory and autonomic involvement. The pathophysiological basis of PSS
      associated neuropathy is still unclear. Dorsal root ganglionitis and peripheral
      nerve vasculitis have been observed on histological examination of biopsy and
      autopsy samples. A few studies have explored the fundamental role of humoral
      autoimmune mechanisms. Small, uncontrolled, treatment trials with numerous
      immunomodulatory agents have reported variable benefit in PSS-associated
      neuropathy, particularly corticosteroids for mononeuritis multiplex and
      intravenous immunoglobulin for small fiber or sensory ataxic neuropathy. SUMMARY:
      The clinical and histological spectrum of neurological manifestations of
      Sjogren's syndrome is becoming clear. The field needs further exploration of
      basic neuroimmunological mechanisms of neural injury, and controlled treatment
      trials.

PMID- 20689427
TI  - Chronic inflammatory demyelinating polyradiculoneuropathy and multifocal motor
      neuropathy: treatment update.
AB  - PURPOSE OF REVIEW: Chronic inflammatory demyelinating polyradiculoneuropathy
      (CIDP) and multifocal motor neuropathy usually respond to immune therapies
      including steroids and plasma exchange for CIDP and high-dose intravenous
      immunoglobulins (IVIgs) for both diseases. Other immune therapies have been used
      to reduce the costs or the side-effects of these therapies, but their efficacy
      was only recently assessed in randomized controlled trials (RCTs). RECENT
      FINDINGS: The prolonged efficacy of IVIg in CIDP has been confirmed in a 48-week
      RCT. Two other RCTs showed that oral methotrexate or intramuscular interferon
      beta were not more effective than placebo in improving the efficacy or reducing
      the dose of IVIg or steroids. In multifocal motor neuropathy, a RCT showed that
      oral mycophenolate mofetil was not more effective than placebo in increasing the
      efficacy or reducing the dose of IVIg. Other immune therapies were assessed in
      open trials in both diseases, but their efficacy remains unclear, even if in some
      patients a possible efficacy of rituximab was reported. Some preliminary studies
      suggest that subcutaneous immunoglobulin may be as effective as IVIg in the
      maintenance therapy of CIDP and multifocal motor neuropathy. SUMMARY: After
      several years of anecdotal reports, a number of RCT have now appeared in CIDP and
      multifocal motor neuropathy, but their results are still insufficient to support
      the use of new therapies in these diseases.

PMID- 20689428
TI  - Sensory neuropathies, from symptoms to treatment.
AB  - PURPOSE OF REVIEW: The present review focuses on recent developments in diagnosis
      and treatment of sensory neuropathies. It does not seek to establish a
      comprehensive classification of sensory neuropathies, nor treatment guidelines
      per se. RECENT FINDINGS: Diagnostic criteria and guidelines have been developed
      for distal symmetric polyneuropathies, small fiber sensory neuropathies and
      sensory neuronopathies. Novel diagnostic tools such as skin biopsies now allow
      diagnosis of small fiber sensory neuropathies. Genetic testing has defined new
      subtypes of mitochondrial neuropathies and inherited neuropathies with sensory
      involvement. Intravenous immunoglobulin and tumor necrosis factor-alpha
      inhibitors show promise for some dysimmune sensory neuropathies or
      neuronopathies. Additional options for management of neuropathic pain are
      emerging. SUMMARY: Diagnostic methods for both acquired and hereditary sensory
      neuropathies have progressed in recent years, leading to earlier and more
      specific diagnoses and a better understanding of disease mechanisms. Much
      progress remains to be made regarding symptomatic and disease-modifying therapy
      for a range of sensory neuropathies, including those due to diabetes, HIV
      infection and from dysimmune or hereditary causes.

PMID- 20689429
TI  - Leptomeningeal metastasis.
AB  - PURPOSE OF REVIEW: Leptomeningeal metastasis occurs in approximately 3-5% of all
      patients with cancer. A contemporary literature review of methods of diagnosis
      and treatment of leptomeningeal metastasis was performed. RECENT FINDINGS: The
      single most important aspect to diagnosis of leptomeningeal metastasis is
      considering and pursuing the diagnosis in a patient with cancer and neurological
      signs and symptoms. Evaluation of leptomeningeal metastasis includes contrast
      enhanced brain and spine magnetic resonance imaging (MRI) and a radionuclide
      cerebrospinal fluid (CSF) flow study if leptomeningeal metastasis-directed
      therapy is being considered. Treatment often requires involved-field radiotherapy
      to bulky or symptomatic disease sites as well as intra-CSF and systemic
      chemotherapy. The use of high-dose systemic therapy may benefit patients with
      leptomeningeal metastasis and obviate the need for intra-CSF chemotherapy. Intra
      CSF drug therapy primarily utilizes one of three chemotherapeutic agents (i.e.
      methotrexate, cytosine arabinoside and thio-TEPA) administered by a variety of
      schedules either by intralumbar or intraventricular drug delivery. Novel and
      increasingly utilized intra-CSF agents in the treatment of leptomeningeal
      metastasis are targeted monoclonal antibodies such as rituximab and trastuzumab.
      SUMMARY: Although treatment of leptomeningeal metastasis is palliative with
      median patient survival of 2-3 months (15% of patients with leptomeningeal
      metastasis survive 1 year), treatment may afford stabilization and protection
      from further neurologic deterioration in patients with leptomeningeal metastasis.

PMID- 20689430
TI  - Imaging and response criteria in gliomas.
AB  - PURPOSE OF REVIEW: To highlight the most recent advances in the imaging of
      gliomas with a focus on high-grade gliomas. In the last several years, MRI and
      PET imaging of the brain have moved beyond anatomic imaging and are now capable
      of probing different aspects of tumor biology and response to treatment. These
      new techniques are increasingly being incorporated into clinical trials and even
      into clinical practice. Therefore, it is important to be familiar with the
      available imaging techniques and their potential uses versus limitations. RECENT
      FINDINGS: In 2010, updated response assessment criteria for high-grade gliomas
      were published. It was the first revision to imaging response criteria for
      gliomas since 1990 and represents an international effort to standardize criteria
      for clinical trials. Although this revision represents an important development,
      there are several promising imaging techniques on the horizon such as vascular
      permeability measurement, perfusion imaging, diffusion imaging, and new PET
      tracers that will continue to improve our understanding of tumor biology.
      SUMMARY: Advances in neuroimaging of brain tumors are enabling investigators to
      noninvasively visualize tumor response to treatment over time. As these tools are
      validated, they will add substantially to our ability to understand glioma
      biology and response to therapy.

PMID- 20689431
TI  - Recent advances of IMiDs in cancer therapy.
AB  - PURPOSE OF REVIEW: Immunomodulatory derivatives of thalidomide (IMiDs) have been
      used for the treatment of myelodysplastic syndrome and multiple myeloma; however,
      the mechanism of action of IMiDs is largely unknown. The purpose of this review
      is to provide an overview of recent findings on the mechanism of action of IMiDs,
      its use as a new treatment modality for various hematologic malignancies, and
      problems associated with stem cell mobilization after lenalidomide treatment.
      RECENT FINDINGS: Recent clinical trials revealed lenalidomide as a promising new
      agent for the treatment of follicular non-Hodgkin's lymphoma (NHL) and also
      diffuse large B-cell lymphoma. Pomalidomide was shown to be even more effective
      in refractory multiple myeloma than lenalidomide. New guidelines for the
      management of venous thromboembolism have been established. The chemokine
      receptor 4 (CXCR4) inhibitor, AMD-3100, is recommended for patients who have
      received lenalidomide and failed to mobilize stem cells after G-SCF and
      cyclophosphamide. Preclinical studies investigated the pleiotropic functions of
      IMiDs, with a particular focus on immune modulation, their effects on new
      targets, stem cells and disruption of plasma cell microenvironment interactions.
      SUMMARY: More and more indications for the use of IMiDs in hematologic
      malignancies have been identified. In order to establish better clinical usage of
      IMiDs, it is of utmost importance to clarify the antitumor mechanism of IMiDs.
      Here, we provide a review on the recent advances in the development of IMiDs. New
      guidelines for venous thromboembolism prophylaxis and stem cell mobilization
      failure associated with lenalidomide treatment have been established.

PMID- 20689432
TI  - Bronchial artery revascularization in lung transplantation: techniques,
      experience, and outcomes.
AB  - PURPOSE OF REVIEW: Lung transplantation (LTX) is routinely performed ignoring the
      bronchial arteries. In this article, we review the published world experience,
      including our own, of LTX with direct bronchial artery revascularization (BAR)
      and describe the anatomy of the bronchial arteries and our surgical technique.
      RECENT FINDINGS: The published experience of LTX with BAR consists of only a few
      small single-institution series, all with good success rates and outcomes. The
      bronchial artery anatomy will allow identification of useful arteries for BAR in
      most donors and double LTX (DLTX) with BAR is almost always possible. For single
      LTX (SLTX), BAR is feasible in about 50%. The surgical techniques for DLTX and
      SLTX with BAR has been well described. Our own combined Copenhagen and Cleveland
      experience, all BAR procedures performed or supervised by G.B.P., include a total
      of 131 LTX with BAR. BAR was performed with a success rate of over 90%, DLTX 95%.
      Success was uniformly associated with normal airway healing and the overall
      Copenhagen 5 and 10-year survival for DLTX with BAR was superior to that reported
      by other institutions after sequential bilateral lung transplantation. SUMMARY:
      LTX with BAR is feasible, successful and well tolerated. Success ensures normal
      airway healing. The Copenhagen experience suggests possible long-term survival
      benefit inviting to a multicenter study to define the role of BAR in LTX.

PMID- 20689433
TI  - Airway complications after lung transplantation can be avoided without bronchial
      artery revascularization.
AB  - PURPOSE OF REVIEW: The major cause of death following lung transplantation in the
      beginning after the first human lung transplantation in 1963 was airway
      dehiscence, representing a major obstacle to widespread use of this treatment
      option. Lung transplantation is unique among all solid organ transplantations,
      since systemic arterial blood supply is not restored during engraftment. In the
      eighties and thereafter the problem of airway healing after lung transplantation
      was the main focus of research. This review focuses on the incidence of airway
      anastomotic complications after lung transplantation and delineates potential
      risk factors. RECENT FINDINGS: Refinements in lung preservation and surgical
      technique have reduced the incidence of airway complications. Reflecting these
      changes, the contemporary rate of anastomotic lesions following lung
      transplantation has dropped from 80% before 1983 to less than 3% with a range of
      2.6-23.8%. Small clinical series of lung transplantation with direct bronchial
      artery revascularization have reported promising early results. However, direct
      bronchial artery revascularization has been considered a difficult and unreliable
      method to be used clinically, as it prolongs the operation and ischemic time,
      increases risk of bleeding, and because of the good results reported from
      transplants without bronchial artery revascularization. At the present time
      (nearly) all transplant centers perform the airway anastomosis without bronchial
      artery revascularization. SUMMARY: Bronchial anastomotic complications can be
      avoided by use of a standardized surgical technique which respects the fact that
      the donor bronchus is poorly vascularized. Prevention of fungal infections with
      aggressive antifungal treatment may play an important additive role.

PMID- 20689434
TI  - How can we improve the long-term outcome after pediatric organ transplantation?

PMID- 20689435
TI  - Bronchial blood supply after lung transplantation without bronchial artery
      revascularization.
AB  - PURPOSE OF REVIEW: This review discusses how the bronchial artery circulation is
      interrupted following lung transplantation and what may be the long-term
      complications of compromising systemic blood flow to allograft airways. RECENT
      FINDINGS: Preclinical and clinical studies have shown that the loss of airway
      microcirculations is highly associated with the development of airway hypoxia and
      an increased susceptibility to chronic rejection. SUMMARY: The bronchial artery
      circulation has been highly conserved through evolution. Current evidence
      suggests that the failure to routinely perform bronchial artery revascularization
      at the time of lung transplantation may predispose patients to develop the
      bronchiolitis obliterans syndrome.

PMID- 20689436
TI  - Cardiac allograft vasculopathy: do adipocytes bridge alloimmune and metabolic
      risk factors?
AB  - PURPOSE OF REVIEW: Cardiac allograft vasculopathy (CAV) is still a major cause of
      chronic graft failure. CAV develops in the coronary arteries as a diffuse,
      concentric expansion of the intima in conjunction with inflammation and fibrosis
      of the adventitia. We review recent publications that could link metabolic and
      immunologic risk factors for CAV.A concept is offered that periarterial
      adipocytes may provide proinflammatory cytokines that augment immune injury of
      the coronary arteries. RECENT FINDINGS: Clinical and experimental evidence
      indicate that some alloantibodies and autoantibodies are associated with CAV.
      Limited data are available on the expression of target antigens on coronary
      arteries at different times after transplantation. Perivascular adipose tissue is
      an abundant source of IL-6, IL-8 and MCP-1. Adding to the inflammatory bias,
      perivascular adipocytes secrete less of the anti-inflammatory adiponectin in
      comparison to other types of fat. Adiponectin modulates expression of adhesion
      molecules on the vascular endothelium. It also decreases neointimal formation in
      arteries following mechanical endovascular injury. SUMMARY: Alterations in the
      balance between proinflammatory and anti-inflammatory cytokines secreted by
      perivascular fat have been implicated in atherosclerosis and restenosis. This
      imbalance may also augment the immune responses in the coronary arteries of
      transplanted hearts.

PMID- 20689437
TI  - Immunosuppression in the sensitized heart transplant recipient.
AB  - PURPOSE OF REVIEW: The proportion of heart transplant candidates who are
      allosensitized has increased over time. Advances in tissue typing and
      immunosuppression have improved the rate of successful transplant in this
      challenging population. Recently published data regarding contemporary approaches
      to desensitization prior to and immunosuppression following transplant are
      summarized. RECENT FINDINGS: Continued progress in measurement and
      characterization of antibodies and strategies to abrogate antibody production
      both prior to and following heart transplant have been encouraging. Updates on
      the role of non-human leukocyte antigen antibodies and the impact of mechanical
      circulatory support on allosensitization are provided. Data on current
      desensitization strategies, including the increasing use of monoclonal
      antibodies, are provided and the potential role of complement inhibitors will be
      reviewed. Increasing experience with potent novel agents is likely to provide the
      opportunity to improve transplant outcomes for highly sensitized patients.
      SUMMARY: Although allosensitized heart transplant candidates remain a management
      challenge, excellent outcomes can be achieved with contemporary approaches.
      Advances in the understanding of B-cell biology are anticipated to further
      broaden options and improve outcomes.

PMID- 20689438
TI  - The case for more effective relationships between psychiatry, religion and
      spirituality.
AB  - PURPOSE OF REVIEW: The purpose of this review is to highlight that the
      indifferent, undecided, and rarely positive attitude of psychiatrists toward the
      relationship between psychiatry, religion and spirituality stands in
      contradiction to extensive data. RECENT FINDINGS: The evidence reveals a largely
      positive relationship between religiosity/spirituality and different indices of
      health. Despite the attitude of psychiatrists in general, the neglect of this
      fact is difficult to justify. However, religious and spiritual beliefs are
      powerful forces and may impart harmful as well as beneficial effects. SUMMARY:
      Whatever disagreements there might be on definition and use, spirituality and
      religion are concerned with the core beliefs, values and experiences of human
      beings. A consideration of their relevance should, therefore, be a central part
      of clinical and academic psychiatry.

PMID- 20689439
TI  - Social aesthetics and the management of addiction.
AB  - PURPOSE OF REVIEW: One of the main causes of nonadherence is that the goals and
      forms of addiction treatment are not sufficiently attractive. To study the
      attractiveness of treatment in clinical practice inevitably means to enter the
      field of social aesthetics. The call for the implementation of social aesthetics
      in practice results in a shift of paradigms in the treatment of patients
      suffering from dependence syndromes. RECENT FINDINGS: The main themes in the
      literature covered by the article focus on the role of social aesthetics in
      medicine in general, as well as on the attractiveness of addiction treatment, in
      particular. SUMMARY: When treatment objectives and programmes become more
      attractive the result will be reduced drop-out rates, and in turn an increase of
      treatment effectiveness. Transferring theory of social aesthetics to clinical
      practice, the Anton Proksch Institute's Orpheus Programme is concerned with
      opening up spaces and creating atmospheres in which it becomes possible for the
      individual addicts to realise their possibilities. The challenge in the
      therapeutic process is not only to recognise the significance of the disorders'
      pathology but also to find ways out of the imagined impossibilities by opening up
      new possibilities and uncovering resources of the suffering human.

PMID- 20689440
TI  - Airway management and morbid obesity.
AB  - Morbidly obese patients present with excess fatty tissue externally on the
      breast, neck, thoracic wall and abdomen and internally in the mouth, pharynx and
      abdomen. This excess tissue tends to make access (intubation, tracheostomy) to
      and patency (during sedation or mask ventilation) of the upper airway and the
      function of the lungs (decreased residual capacity and aggravated ventilation
      perfusion mismatch) worse than in lean patients. Proper planning and preparation
      of airway management is essential, including elevation of the patient's upper
      body, head and neck. Preoxygenation is mandatory in morbidly obese patients and
      should be followed by actions to counteract atelectasis formation. The decision
      as to weather to use a rapid sequence induction, an awake intubation or a
      standard induction with hypnotics should depend on the thorough airway
      examination and comorbidity and should not be based solely on whether morbid
      obesity is present or not. It is important to ensure sufficient depth of
      anaesthesia before initiating manipulation of the airway because inadequate
      anaesthesia depth predisposes to aspiration if airway management becomes
      difficult. The intubating laryngeal mask airway is more efficient in the morbidly
      obese patients than in lean patients and serves as a rescue device for both
      failed ventilation and failed intubation. In the 24 h following anaesthesia,
      morbidly obese patients experience frequent oxygen desaturation periods that can
      be counteracted by continuous positive airway pressure, noninvasive ventilation
      and physiotherapy.

PMID- 20689441
TI  - Cardiopulmonary exercise testing: a review of methods and applications in
      surgical patients.
AB  - Cardiopulmonary exercise (CPX) testing has a number of medical applications,
      including the assessment of heart failure and the investigation of unexplained
      breathlessness. Over the past decade, it has become an important preoperative
      assessment tool to evaluate functional capacity and predict outcomes in patients
      undergoing both cardiac and noncardiac surgery. A CPX test is an incremental
      exercise test during which respiratory variables, including oxygen uptake and
      carbon dioxide excretion are measured and the ECG is monitored. Among the
      variables reported from a CPX test are oxygen uptake at anaerobic threshold and
      peak oxygen uptake. A limited functional capacity as indicated by a low anaerobic
      threshold or VO(2peak) has been shown to be associated with an increased
      incidence of perioperative complications in a number of surgical settings. Other
      reported variables, including the ventilatory equivalents for oxygen (VE/VO(2))
      and carbon dioxide (VE/VCO(2)) and the millilitre of oxygen delivered per
      heartbeat or oxygen pulse [VO(2)/heart rate (HR)] may give indications as to the
      reasons for exercise limitation. ECG evidence of myocardial ischaemia with
      increasing workload is also an important indicator of increased perioperative
      risk. As a noninvasive, low-risk, test of the integrated responses to increasing
      cardiovascular stress, anaesthesiologists involved in preoperative assessment
      should have an understanding of its current uses and test outcomes. This review
      presents the physiological basis for CPX testing, methodology, advantages over
      other preoperative tests of cardiovascular function and guidance on the
      interpretation of CPX results in the perioperative setting.

PMID- 20689442
TI  - Polyarticular gout attacks following cerebrovascular accidents: is hemiparesis in
      fact protective? 2 cases and a review of the literature.
AB  - Cerebrovascular disease appears to have implications on rheumatic diseases,
      including gout. Accumulating evidence suggests that hemiparesis exerts a
      protective effect against gout via the down-regulation of mechanical and neural
      modulators of inflammation in neurologically impaired extremities. We present 2
      divergent cases of unilateral gout following cerebrovascular events. One patient
      with a hemorrhagic stroke developed polyarticular gout only on the ipsilateral
      side to his hemiparesis, while another patient with basilar artery thrombosis and
      locked-in syndrome suffered a polyarticular gout flare only on the side that had
      regained limited function. As suggested by these cases, the effect of hemiparesis
      on gout is complex. Further insight into the interplay between gouty flares and
      hemiparesis may lead to novel therapeutic strategies for gout.

PMID- 20689443
TI  - Time to treatment in rheumatoid arthritis: factors associated with time to
      treatment initiation and urgent triage assessment of general practitioner
      referrals.
AB  - BACKGROUND: The importance of early diagnosis and treatment of rheumatoid
      arthritis (RA) is increasingly being recognized. This requires accurate triaging
      of suspected RA referrals from primary care and expedient assessment of these
      patients in secondary care. OBJECTIVES: To assess the factors associated with
      urgent triage for first specialist appointment and early disease modifying agents
      in rheumatic disease treatment. METHODS: The general practitioner (GP) referrals
      to a single rheumatology service from 128 new RA patients were assessed for their
      information content and triage allocation by the Rheumatologists. Information on
      symptoms, signs, and investigation results were collected. Factors associated
      with urgent triage allocation, time to treatment, and a GP requesting urgency
      were assessed. RESULTS: Median time from symptom onset to treatment was 6.1
      months. Triage allocation to urgent was associated with earlier treatment
      (difference of 97 days, P = 0.003). GP perception of urgency (odds ratio = 13.34,
      95% confidence interval: 2.20-81.02) was independently associated with an urgent
      triage allocation by the triaging rheumatologist. Swollen joints and a raised C
      reactive protein predicted GP request for urgency. CONCLUSION: Triage is
      important to facilitate early treatment; however, rheumatologists in this service
      are not currently triaging suspected RA referrals with reference to known poor
      prognostic indicators. Several interventions could improve both informative
      referrals and triaging of referrals to decrease time to diagnosis and treatment.
      These interventions could include public education, GP education sessions with
      associated distribution of referral guidelines, and reminding triaging
      rheumatology clinicians about the available prognostic factors often present in
      GP referrals that assist with correct triage.

PMID- 20689444
TI  - Hypersomnolence and sleep disorders in a rheumatic disease patient population.
AB  - OBJECTIVES: There is increasing awareness of the importance of sleep in health
      maintenance. Our primary objective was to evaluate prevalence of excess daytime
      sleepiness in a rheumatic disease patient population. Secondary objectives
      included evaluation of prevalence of abnormal sleep quality and primary sleep
      disorders. METHODS: Consecutive Rheumatology clinic patients were invited to
      participate in a self-administered questionnaire study. Included were measures
      for pain, fatigue, and global functioning, modified Health Assessment
      Questionnaire, Epworth Sleepiness Score (ESS), Pittsburgh Sleep Quality Index
      (PSQI), Berlin Score, diagnostic criteria for restless legs syndrome (RLS),
      Centre for Epidemiologic Studies Depression score (CES-D), stress scores, and the
      short form-36 quality of life instrument. RESULTS: Of 507 consecutive patients
      invited to participate, 423 agreed. Mean age was 52.1 years; 26% were male.
      Prevalence of excessive sleepiness (ESS >10) was 25.7%, abnormal sleep quality
      (PSQI >5) was 67.3%, high risk for obstructive sleep apnea Berlin scores were
      present in 35.2% and 24% of participants met criteria for RLS. Significantly
      worse pain, fatigue, global function, short form-36 summary scores, modified
      Health Assessment Questionnaire, depression, and stress scores were present in
      patients with higher ESS and PSQI scores. No significant differences in sleep
      assessment scores were observed between specific rheumatic disease groups.
      CONCLUSIONS: Our findings suggest a high prevalence of unrecognized
      hypersomnolence, poor sleep quality, and primary sleep disorders in rheumatology
      patients. We suggest evaluation of sleep health be incorporated into standard
      clinical assessments of all rheumatology patients. We would recommend this
      evaluation include the ESS and the criteria for RLS.

PMID- 20689445
TI  - Functional heterogeneity of osteopontin isoforms in non-small cell lung cancer.
AB  - INTRODUCTION: Osteopontin (OPN) is a multifunctional protein with an important
      but poorly understood role in non-small cell lung cancer (NSCLC) pathogenesis.
      Moreover, the role of the three known mRNA isoforms (OPNa, OPNb, and OPNc) has
      not been reported. We hypothesize that OPN isoforms play different roles in
      determining the metastatic potential of NSCLC. METHODS: We amplified mRNA for
      each OPN isoform in NSCLC tumors and matched normal lung. The functional impact
      of each isoform was evaluated by transfecting cDNA plasmids specific to each
      isoform into NSCLC cell lines and comparing behavior to empty vector controls in
      scratch closure, cell proliferation, soft-agar colony formation, and Matrigel
      invasion assays. Gene array was used to evaluate differences in downstream
      targets and was compared with a panel of markers for epithelial-mesenchymal
      transition (EMT). RESULTS: OPNa expression was increased in 91% of NSCLC tumors
      compared with matched lung. OPNa overexpression significantly increased activity
      in scratch closure, proliferation, soft-agar colony formation, and Matrigel
      invasion assays compared with controls in all cell lines. OPNb overexpression
      produced a less significant modulation of function. OPNc overexpression
      significantly decreased activity in proliferation, colony formation, and invasion
      assays compared with controls. Expression arrays revealed an increase in EMT with
      OPNa overexpression but not OPNc. Differences were validated by quantitative
      reverse transcriptase-polymerase chain reaction. CONCLUSIONS: Overexpression of
      the individual OPN isoforms in NSCLC results in divergent functional phenotypes.
      OPNa produced an aggressive phenotype, whereas OPNc produced a more indolent
      phenotype. Exon 4, which is transcribed in OPNa but absent in OPNc, may be
      central to this phenomenon and could serve as a target for isoform-specific
      inhibition of OPN in NSCLC.

PMID- 20689446
TI  - Dorsiflexion capacity affects achilles tendon loading during drop landings.
AB  - PURPOSE: Evidence suggests a link between decreased dorsiflexion range of motion
      (DROM) and injury risk during landings. The purpose of this study was to
      determine the effect of weight-bearing DROM on ankle mechanics during drop
      landings. METHODS: Forty-eight men (mean +/- SD = 22.5 +/- 4.7 yr) were measured
      for DROM. Participants performed drop landings onto a force platform at two
      vertical descent velocities (2.25 +/- 0.15 and 3.21 +/- 0.17 m.s(-1)), while EMG
      activity of four shank muscles and three-dimensional ankle joint kinematics were
      recorded. Participants were classified into low (37.7 degrees  +/- 2.5 degrees )
      and high (48.4 degrees  +/- 2.5 degrees ) DROM groups. RESULTS: Ground reaction
      force, EMG, dorsiflexion angle, plantarflexion moment, and Achilles tendon force
      outcome variables were all equivalent for the two DROM groups during each landing
      condition. However, the low DROM group performed each landing condition at a
      significantly greater percentage of their DROM and displayed significantly more
      ankle eversion throughout most of the movement. The low and high DROM groups
      displayed DROM percentages of 27 +/- 11 and 10 +/- 11 (P = 0.013), 32 +/- 9 and
      23 +/- 9 (P = 0.056), 60 +/- 13 and 46 +/- 13 (P = 0.004), and 66 +/- 16 and 54
      +/- 9 (P = 0.003) when they encountered the peak plantarflexion moments, Achilles
      tendon force, eversion angles, and dorsiflexion angles, respectively. CONCLUSION:
      Participants with a low DROM absorbed the landing impact forces with their
      plantarflexor muscle-tendon units in a more lengthened and everted position.
      Athletes with a low DROM may be more likely to regularly overload their
      plantarflexor muscle-tendon units, thereby potentially exposing themselves to a
      higher likelihood of incurring injuries such as Achilles tendinopathy.

PMID- 20689447
TI  - Associations among strength, steadiness, and hand function across the adult life
      span.
AB  - INTRODUCTION: Age-related differences in force steadiness have been extensively
      examined and used as an index of motor function. However, the functional
      relevance of steadiness remains unclear. PURPOSE: The aim here was to evaluate
      the relations among hand strength, steadiness, and function across the adult life
      span. METHODS: Seventy-five adults (45 women; 18-89 yr) performed three strength,
      two steadiness, and four functional tests with both hands. Strength was measured
      during index finger abduction, precision pinch, and handgrip, and steadiness was
      measured during index finger abduction and precision pinch. Functional tests
      included the Grooved Pegboard test, the game OperationTM, a scissor task, and a
      tracing task. RESULTS: Moderate correlations were observed between both
      steadiness tasks and performance on the Grooved Pegboard test (R(2) = 0.57 and
      R(2) = 0.46, respectively) and OperationTM (R(2) = -0.47 and R(2) = -0.57,
      respectively). CONCLUSIONS: The relation between measures of steadiness and hand
      function suggests that the physiological mechanisms responsible for differences
      in steadiness also contribute to differences in the performance of fine motor
      tasks with the hand.

PMID- 20689448
TI  - Exercise autonomous motivation predicts 3-yr weight loss in women.
AB  - PURPOSE: This study evaluated exercise-related predictors of successful long-term
      weight control in women by analyzing the extent to which sustained exercise
      participation and self-determination theory (SDT)-based exercise motivation
      variables mediated the impact of a behavioral weight control intervention on 3-yr
      weight change. METHODS: Longitudinal randomized controlled trial consisting of a
      1-yr SDT-based intervention and a 2-yr follow-up with 221 female participants
      (means +/- SD: age = 37.6 +/- 7 yr, body mass index = 31.6 +/- 4.1 kg.m(-2)). The
      tested model incorporated experimentally manipulated perceived need support,
      motivational regulations, and 2-yr exercise adherence as mediators of the
      intervention's impact on 3-yr weight change. Paths were tested using partial
      least squares analysis. Where there were significant intervening paths, tests of
      mediation were conducted. RESULTS: Treatment had significant effects on 1- and 2
      yr autonomous regulations, 2-yr physical activity, and 3-yr weight change, fully
      mediated by the tested paths (effect ratio = 0.10-0.61). Moderate and vigorous
      exercise at 2 yr had a significant effect (P < 0.001) on weight loss success at 3
      yr and partially mediated the effect of treatment on weight change. The 2-yr
      autonomous regulation effects on follow-up weight change were only partially
      mediated by physical activity (effect ratio = 0.42). CONCLUSIONS: This
      application of SDT to physical activity and weight management showed that not all
      types of motivation predict long-term behavioral outcomes and that sustained
      moderate and vigorous exercise mediated long-term weight change. It provides
      strong evidence for a link between experimentally increased autonomous motivation
      and exercise and long-term weight loss maintenance. Results highlight the
      importance of interventions targeting the internalization of exercise behavioral
      regulation and making exercise and physical activity positive and meaningful
      experiences rather than simply focusing on immediate behavior change in
      overweight/obese women.

PMID- 20689449
TI  - Objectively measured physical activity in a diverse sample of older urban UK
      adults.
AB  - BACKGROUND: There are many health and social benefits of physical activity (PA)
      for older adults, but little is known about their activity patterns. PURPOSE: The
      purpose of this study was to objectively assess the PA patterns of older adults
      and the lifestyle and demographic factors associated with PA. METHODS:
      Participants (N = 230, aged 78.1 yr) recruited from medical practices (between
      2007 and 2008) completed journey logs and wore accelerometers for 7 d. Mean daily
      steps, counts per minute (CPM), minutes of sedentary, light, or moderate-to
      vigorous PA (MVPA), and frequency of journeys were analyzed (in 2009). RESULTS:
      Younger participants (age = 70-74.9 yr) were significantly (P < 0.001) more
      active (5660.8 steps per day) than older participants aged 80+ yr (3409.6 steps
      per day). Men performed significantly (P = 0.035) more minutes MVPA than women
      (23.1 vs 13.8 min MVPA per day). Normal weight participants were significantly (P
      < 0.05) more active (5368.9 steps per day) than overweight (4532.7 steps per day)
      and obese (3251.4 steps per day) groups. Those performing many journeys (>11.6
      journeys per week) were significantly (P < 0.001) more active (5838.2 steps per
      day) than those performing few (<7 journeys per week) (3094.2 steps per day). PA
      was significantly (P < 0.001) greater in mornings (259.3 CPM) than afternoons
      (181.8 CPM) and evenings (102.5 CPM). Sundays were significantly (P < 0.001) less
      active (3331.7 steps per day) than Saturdays (4193.1 steps per day) and weekdays
      (4623.5 steps per day). Light activity was significantly (P = 0.005) higher in
      spring (3.4 h.d(-1)) than that in winter (2.7 h.d(-1)). CONCLUSIONS: Older
      adults' PA patterns differ by age, gender, and weight status. Daily journeys are
      associated with more activity for all groups. Variability in volume of activity
      is high for all age groups. Temporal patterns of PA indicate that journeys out of
      the house for shopping and personal business are important in their contribution
      to PA levels.

PMID- 20689450
TI  - Effects of flexibility training on eccentric exercise-induced muscle damage.
AB  - PURPOSE: This study investigated whether flexibility training would attenuate
      muscle damage induced by maximal eccentric exercise. METHODS: Thirty untrained
      young men were allocated to static stretching (SS), proprioceptive neuromuscular
      facilitation (PNF), or control group (n = 10 per group). The SS consisted of 30
      sets of a 30-s standard SS with a 30-s rest between sets, and the PNF included 5
      sets of the 30-s standard SS followed by 3 sets of three "contract-relax-agonist
      contract" procedures. These were performed three times a week for 8 wk, and all
      subjects performed six sets of 10 maximal isokinetic (30 degrees .s) lengthening
      contractions of the knee flexors after the 8-wk training or 8 wk after the
      baseline measures (control). Changes in indirect markers of muscle damage before
      and for 5 d after the eccentric exercise were compared among the groups. RESULTS:
      The range of motion (ROM) of the hip joint increased by 25 degrees , and the
      optimum angle of the knee flexors shifted (P < 0.05) to a longer muscle length by
      10 degrees  after training, without significant differences between SS and PNF.
      No significant changes in these variables were evident for the control group.
      Compared with the control group, the SS and PNF groups showed significantly (P <
      0.05) smaller decreases and faster recovery of knee flexor muscle strength and
      smaller changes in optimum angle, ROM, muscle soreness, and plasma creatine
      kinase activity and myoglobin concentration without significant differences
      between the groups. The preeccentric exercise ROM or optimum angle was
      significantly (P < 0.05) correlated with the changes in the muscle damage
      markers. CONCLUSIONS: These results suggest that both SS and PNF training are
      effective in attenuating eccentric exercise-induced muscle damage and that
      flexible muscles are less susceptible to the damage.

PMID- 20689451
TI  - Exercise and NSAIDs: effect on muscle protein synthesis in patients with knee
      osteoarthritis.
AB  - PURPOSE: The purpose of this study was to determine muscle and tendon protein
      fractional synthesis rates (FSR) at rest and after a one-legged kicking exercise
      in patients with knee osteoarthritis (OA) receiving either placebo or
      nonsteroidal anti-inflammatory drugs (NSAIDs). METHODS: Twenty patients with knee
      OA (50-70 yr) were enrolled. For each of the 3 days before the exercise
      intervention, 9 patients were administered NSAIDs (1200 mg), and 11 patients were
      administered placebo in a double-blinded manner. Each patient performed 60 min of
      one-legged kicking at 55% of workload maximum while the contralateral leg
      remained rested. Twenty-four hours after exercise, we determined circulating
      concentrations of inflammatory parameters and measured FSR of myofibrillar and
      sarcoplasmic protein fractions of vastus lateralis muscle and patellar tendon
      collagen protein by the direct incorporation method using a flooding dose of
      13C/12C-proline. RESULTS: Circulating levels of prostaglandin F2alpha were lower
      in the NSAID group compared with the placebo group (P < 0.05). There was an
      overall significant effect of exercise on FSR in muscle myofibrillar (P = 0.003)
      and sarcoplasmic protein (P = 0.026) but not in tendon collagen protein (P =
      0.52). No overall significant effect of the drug was seen on either of the tissue
      protein fractions (P > 0.05) or on the interaction between the drug and exercise
      on FSR in tendon collagen (P = 0.21), muscle myofibrillar (P = 0.68), or
      sarcoplasmic protein, FSR (P = 0.16). CONCLUSION: In elderly patients with knee
      OA, an acute bout of moderate exercise significantly increases FSR of muscle
      myofibrillar and sarcoplasmic protein, but not tendon collagen, 24 h after
      exercise. NSAID administration in patients with knee OA reduced the level of
      circulating prostaglandin F2alpha but did not diminish the exercise-induced
      response of muscle contractile protein FSR. However, we cannot exclude that a
      minor inhibition of muscle sarcoplasmic proteins may have been present with NSAID
      treatment. This study suggests that muscle hypertrophy after long-term training
      is not influenced by NSAIDs.

PMID- 20689452
TI  - Effects of vibrations on gastrocnemius medialis tissue oxygenation.
AB  - PURPOSE: Whole-body vibrations are known to affect muscle activity and tissue
      oxygenation, but some energetic aspects are still poorly understood. This study
      investigates the effects of whole-body vibration on gastrocnemius muscle oxygen
      utilization rate and tissue oxygenation dynamics during exercise. METHODS: The
      effects of vibration on gastrocnemius medialis muscle oxygenation were
      investigated during a dynamic exercise on a sample of 16 active male subjects
      (age = 26.3 +/- 5.1 yr, mass = 71.2 +/- 4.8 kg (mean +/- SD)). Both arterially
      occluded (AO) and nonoccluded (N/O) conditions were investigated. Tissue
      oxygenation was monitored with a near-infrared spectrometer. Oxygen utilization
      rate and tissue oxygenation recovery were computed as the slopes of the
      regression line of the oxygenation decay and recovery, respectively. A fast
      Fourier transform (FFT) was used to determine the frequency spectrum of the
      oxygen saturation data. EMG activity was monitored using bipolar EMG electrodes.
      A windowed root mean square analysis was used to monitor the amplitude of the EMG
      signal. RESULTS: A statistically significant increase of 15% (P < 0.05) in oxygen
      utilization rate was found for the vibration condition in the AO leg but not in
      the N/O leg. The oxygenation recovery rate for the vibration condition was 34%
      higher (P < 0.05) than that for the control condition. A low-frequency periodic
      oscillation (T ~ 10 s) in the tissue oxygenation data was determined from the FFT
      spectrum. A statistically significant decrease in the oscillation frequency was
      noticed for the vibration condition compared with the control. CONCLUSIONS:
      Vibrations increased the oxygen utilization rate during a dynamic exercise. The
      oxygenation recovery rate increased with vibrations. The low-frequency
      oscillation of the oxygenation was attributed to the periodic changes in tissue
      blood flow, and this seems to be influenced by vibrations.

PMID- 20689453
TI  - Lower extremity joint kinematics during stair climbing in knee osteoarthritis.
AB  - PURPOSE: Knee osteoarthritis (OA) is one of the most prevalent chronic lower
      extremity diseases, causing profound limitation of movement and ability to
      perform activities of daily living. The purpose of this study was to compare
      various hip, knee, and ankle joint kinematic variables between knee OA subjects
      and matched healthy controls during stair ascent and descent. METHODS: Eighteen
      subjects with knee OA (age = 60.2 +/- 9.9 yr, mass = 90.3 +/- 16.7 kg, height =
      168.4 +/- 9.9 cm) and 18 healthy matched controls (age = 60.3 +/- 10.7 yr, mass =
      81.1 +/- 21.2 kg, height = 168.3 +/- 11.9 cm) participated in the study. Subjects
      performed five ascending and descending trials on a custom-built staircase while
      their motion was captured three-dimensionally using an eight-camera optical video
      motion capture system. RESULTS: Significant group * direction interactions were
      found for average hip flexion angle at foot strike (P = 0.04), for average ankle
      adduction angle at foot strike (P = 0.01), and for peak ankle dorsiflexion angle
      during support (P = 0.05) and swing (P = 0.01). Specifically, knee OA and control
      subjects demonstrated greater hip flexion angle at foot strike and ankle
      dorsiflexion angle during swing but showed smaller ankle dorsiflexion angle
      during support during stair ascent compared with descent. Furthermore, compared
      with controls, knee OA patients demonstrated greater hip abduction at foot strike
      (-3.1 degrees  +/- 3.9 degrees ) and smaller peak knee flexion during support
      (60.4 degrees  +/- 5.0 degrees ) and swing (86.7 degrees  +/- 5.4 degrees ). Time
      of peak hip abduction (34.2% +/- 7.1%), hip flexion (7.0% +/- 12.3%), knee
      flexion (69.8% +/- 4.6%), dorsiflexion (51.4% +/- 2.9%), and ankle adduction
      (37.3% +/- 20.8%) during support occurred later in the gait cycle for knee OA
      patients. CONCLUSIONS: These data demonstrate that knee OA directly influences
      specific knee joint kinematics and induces kinematic alterations at the hip and
      ankle perhaps to compensate for the existing knee joint pathology.

PMID- 20689455
TI  - Effects of a fruit/berry/vegetable supplement on muscle function and oxidative
      stress.
AB  - PURPOSE: This study tested the effectiveness of a fruit, berry, and vegetable
      concentrate (FVC), Juice Plus+(r) (NSA LLC, Collierville, TN), supplement on
      muscle function and oxidative stress in response to an acute bout of eccentric
      exercise (EE). METHODS: Forty-one healthy volunteers (age = 18-35 yr) were
      randomly assigned to either a placebo (P) or an FVC treatment taking capsules for
      28 d (6 d(-1)) before EE and for the next 4 d. All subjects completed four sets
      of 12 repetitions of eccentric elbow flexion with their nondominant arm. Blood,
      muscle soreness (MS), range of motion (ROM), and maximal isometric force (MIF) of
      the elbow flexors were obtained before and immediately after exercise and at 2,
      6, 24, 48, and 72 h postexercise. Plasma was analyzed for creatine kinase (CK),
      lipid hydroperoxides, malondialdehyde (MDA), and protein carbonyls (PC).
      Glutathione ratio was determined from whole-blood extracts. RESULTS: MS, ROM,
      MIF, and plasma CK demonstrated significant time effects independent of
      treatment. MS and plasma CK increased over time, whereas ROM and MIF decreased
      over time. There was a significant time and time * treatment effect for plasma PC
      and MDA. PC and MDA increased over time in the P group (P < 0.01) but were not
      significantly altered in the FVC-treated group at any time. No significant
      changes were noted in lipid hydroperoxides. The glutathione ratio was elevated
      immediately postexercise in both groups (P < 0.01) and elevated 6 h postexercise
      with P compared with the FVC-treated group (P < 0.05). CONCLUSION: This study
      reports that 4 wk of pretreatment with an FVC can attenuate blood oxidative
      stress markers induced by EE but had no significant impact on the functional
      changes related to pain and muscle damage.

PMID- 20689454
TI  - Hamstring musculotendon dynamics during stance and swing phases of high-speed
      running.
AB  - INTRODUCTION: Hamstring strain injuries are common in sports that involve high
      speed running. It remains uncertain whether the hamstrings are susceptible to
      injury during late swing phase, when the hamstrings are active and lengthening,
      or during stance, when contact loads are present. In this study, we used forward
      dynamic simulations to compare hamstring musculotendon stretch, loading, and work
      done during stance and swing phases of high-speed running. METHODS: Whole-body
      kinematics, EMG activities, and ground reactions were collected as 12 subjects
      ran on an instrumented treadmill at speeds ranging from 80% to 100% of maximum
      (avg max speed = 7.8 m.s(-1)). Subject-specific simulations were then created
      using a whole-body musculoskeletal model that included 52 Hill-type musculotendon
      units acting about the hip and the knee. A computed muscle control algorithm was
      used to determine muscle excitation patterns that drove the limb to track
      measured hip and knee sagittal plane kinematics, with measured ground reactions
      applied to the limb. RESULTS: The hamstrings lengthened under load from 50% to
      90% of the gait cycle (swing) and then shortened under load from late swing
      through stance. Although peak hamstring stretch was invariant with speed, lateral
      hamstring (biceps femoris) loading increased significantly with speed and was
      greater during swing than stance at the fastest speed. The biarticular hamstrings
      performed negative work on the system only during swing phase, with the amount of
      negative work increased significantly with speed. CONCLUSION: We concluded that
      the large inertial loads during high-speed running appear to make the hamstrings
      most susceptible to injury during swing phase. This information is relevant for
      scientifically establishing muscle injury prevention and rehabilitation programs.

PMID- 20689456
TI  - Knee kinematic profiles during drop landings: a biplane fluoroscopy study.
AB  - INTRODUCTION: The six degrees of freedom knee motion during dynamic activities is
      not well understood. PURPOSE: Biplane fluoroscopy was used to measure the three
      dimensional rotations and translations of healthy knees during stiff drop
      landings and to determine the relationships between three-dimensional rotations
      and anterior (ATT) and lateral tibial translations (LTT). METHODS: Six males
      performed stiff drop landings from 40 cm while being filmed using a high-speed,
      biplane fluoroscopy system. Initial, peak, and excursions for rotations and
      translations were calculated, and relationships and changes in these variables
      were assessed (alpha = 0.05). RESULTS: Knee flexion at contact was 13.9 degrees 
      +/- 9.2 degrees  (mean +/- SD) and increased to a peak of 44.0 degrees  +/- 17.2
      degrees  with an excursion of 31.5 degrees  +/- 14.1 degrees . Knee varus/valgus
      angle at contact was -0.3 degrees  +/- 1.8 degrees  varus; subjects progressed
      into a mean peak valgus position of 1.5 degrees  +/- 0.9 degrees  with total
      excursion of 2.5 degrees  +/- 0.9 degrees . Four of six subjects landed
      externally rotated (2.5 degrees  +/- 3.0 degrees ); two landed internally rotated
      (-4.9 degrees  +/- 1.5 degrees ), yielding a contact angle of -2.4 degrees  +/-
      3.0 degrees  of internal rotation, a peak internal rotation of -5.5 degrees  +/-
      6.0 degrees , and excursion of 3.1 degrees  +/- 5.5 degrees . Peak ATT were 4.3
      +/- 0.7 mm (excursion = 2.1 +/- 0.9 mm), occurring within 50 ms after contact.
      Peak LTT were 1.5 +/- 1.4 mm (excursion = 2.6 +/- 1.6 mm). Significant
      regressions were found between ATT and knee valgus angle (r2 = 0.39, P = 0.006),
      between LTT and internal rotation (r2 = 0.96, P < 0.0001), and between LTT and
      knee valgus angle (quadratic, r2 = 0.90, P < 0.0001). CONCLUSION: This study
      provides a direct correlation between knee valgus angle with knee ATT and LTT
      during drop landings.

PMID- 20689457
TI  - Influence of ingesting versus mouth rinsing a carbohydrate solution during a 1-h
      run.
AB  - PURPOSE: To investigate the influence of ingesting versus mouth rinsing a
      carbohydrate-electrolyte solution on 1-h running performance. METHODS: After a 14
      to 15-h fast, 10 endurance-trained male runners (mean +/- SD: VO2peak = 65.0 +/-
      4.4 mL.kg(-1).min(-1)) completed three 1-h performance runs separated by 1 wk. In
      random order, runners ingested either a 8-mL.kg(-1) body mass of either a 6.4%
      carbohydrate-electrolyte solution (CHO) or a placebo solution (P) 30 min before
      or a 2-mL.kg(-1) body mass at 15-min intervals throughout the 1-h run. On a
      separate occasion, runners mouth rinsed (R) a 6.4% CHO, i.e., without ingestion,
      at the same times as in the ingestion trials. RESULTS: Total distances covered in
      the CHO, P, and R trials were 14,515 +/- 756, 14,190 +/- 800, and 14,283 +/- 758
      m, respectively. Runners covered 320 m more (90% confidence interval = 140-510 m,
      P = 0.01) during the CHO trial compared with the P trial and 230 m more (90%
      confidence interval = 83-380 m, P = 0.019) in comparison with the R trial. There
      was no difference in n distance covered between the R and P trials (P = 1.0).
      CONCLUSIONS: A greater distance was covered after the mouth rinse and ingestion
      of a 6.4% CHO during a 1-h performance run than when mouth rinsing the same
      solution or mouth rinsing followed by the ingestion of the same volume of a
      placebo solution.

PMID- 20689458
TI  - Can a clinical test of reaction time predict a functional head-protective
      response?
AB  - PURPOSE: Reaction time is commonly prolonged after a sport-related concussion.
      Besides being a marker for injury, a rapid reaction time is necessary for
      protective maneuvers that can reduce the frequency and severity of additional
      head impacts. The purpose of this study was to determine whether a clinical test
      of simple visuomotor reaction time predicted the time taken to raise the hands to
      protect the head from a rapidly approaching ball. METHODS: Twenty-six healthy
      adult participants recruited from campus and community recreation and exercise
      facilities completed two experimental protocols during a single session: a manual
      visuomotor simple reaction time test (RT(clin)) and a sport-related head
      protective response (RT(sprt)). RT(clin) measured the time required to catch a
      thin vertically oriented device on its release by the tester and was calculated
      from the distance the device fell before being arrested. RT(sprt) measured the
      time required to raise the hands from waist level to block a foam tennis ball
      fired toward the subject's face from an air cannon and was determined using an
      optoelectronic camera system. A correlation coefficient was calculated between
      RT(clin) and RT(sprt), with linear regression used to assess for effect
      modification by other covariates. RESULTS: A strong positive correlation was
      found between RT(clin) and RT(sprt) (r = 0.725, P < 0.001) independent of age,
      gender, height, or weight. CONCLUSIONS: RT(clin) is predictive of a functional
      sport-related head-protective response. To our knowledge, this is the first
      demonstration of a clinical test predicting the ability to protect the head in a
      simulated sport environment. This correlation with a functional head-protective
      response is a relevant consideration for the potential use of RT(clin) as part of
      a multifaceted concussion assessment program.

PMID- 20689459
TI  - Respiratory symptoms and bronchial responsiveness in competitive swimmers.
AB  - PURPOSE: A high prevalence of bronchial hyperresponsiveness (BHR) and respiratory
      symptoms has been reported among competitive swimmers. From the 2002 Winter
      Olympics, BHR measurements or bronchodilator reversibility have been required for
      approved use of beta2-agonists in sports. The first aim of this study was to
      evaluate the relationship among respiratory symptoms in young elite swimmers,
      eucapnic voluntary hyperpnea (EVH), and the inhaled dose of methacholine, causing
      a 20% decrease in forced expiratory volume in 1 s (FEV1; PD(20 methacholine)).
      The second aim of this study was to assess the repeatability of the EVH test.
      METHODS: For this study, 15 male and 9 female adolescent elite swimmers, aged 15
      to 25 yr, performed one PD(20 methacholine) test and two EVH tests in a
      randomized order. Dry air containing 5% CO2 was inhaled for 6 min with a target
      ventilation of >=85% of maximum voluntary ventilation (minimum = 65%). PD(20
      methacholine) <=2 MUmol and EVH with FEV1 reduction >=10% were considered
      positive. Respiratory symptoms and medication were reported in the modified
      AQUA2008 questionnaire. RESULTS: Twenty swimmers (83%) reported respiratory
      symptoms, 13 (65%) of them had a positive provocation test. Fourteen (58%) had at
      least one positive test to either EVH or PD(20 methacholine); three had only one
      positive EVH test. One athlete had BHR without symptoms. The sensitivity of PD(20
      methacholine) <=2 MUmol for respiratory symptoms was 50% versus 60% and 47.37%
      for the two EVH tests, respectively, and 75% for PD(20 methacholine) <=4 MUmol.
      The Bland-Altman plot of the two EVH tests showed a consistent distribution, with
      only one subject outside the limits of agreement. CONCLUSIONS: BHR was frequently
      found among adolescent competitive swimmers. PD(20 methacholine) <=2 MUmol and
      EVH >= 10% compared well, but PD(20 methacholine) <=4 MUmol had the highest
      sensitivity for respiratory symptoms. The EVH test has high repeatability but is
      very expensive and uncomfortable to perform.

PMID- 20689460
TI  - Individual responses to combined endurance and strength training in older adults.
AB  - PURPOSE: A combination of endurance and strength training is generally used to
      seek further health benefits or enhanced physical performance in older adults
      compared with either of the training modes alone. The mean change within a
      training group, however, may conceal a wide range of individual differences in
      the responses. The purpose, therefore, was to examine the individual trainability
      of aerobic capacity and maximal strength, when endurance and strength training
      are performed separately or concurrently. METHODS: For this study, 175 previously
      untrained volunteers, 89 men and 86 women between the ages of 40 and 67 yr,
      completed a 21-wk period of either strength training (S) twice a week, endurance
      training (E) twice a week, combined training (ES) four times per week, or served
      as controls. Training adaptations were quantified as peak oxygen uptake (VO2peak)
      in a bicycle ergometer test to exhaustion and maximal isometric bilateral leg
      extension force (MVC) in a dynamometer. RESULTS: A large range in training
      responses, similar to endurance or strength training alone, was also observed
      with combined endurance and strength training in both DeltaVO2peak (from -8% to
      42%) and DeltaMVC (from -12% to 87%). There were no significant correlations
      between the training responses in VO2peak and MVC in the E, S, or especially in
      the ES group, suggesting that the same subjects did not systematically increase
      both aerobic capacity and maximal strength. CONCLUSIONS: The goal of combined
      endurance and strength training--increasing both aerobic capacity and maximal
      strength simultaneously--was only achieved by some of the older subjects. New
      means are needed to personalize endurance, strength, and especially combined
      endurance and strength training programs for optimal individual adaptations.

PMID- 20689461
TI  - Catecholamine response to exercise in obese, overweight, and lean adolescent
      boys.
AB  - INTRODUCTION: The aim of this study was to examine the effect of body fat
      percentage on the plasma catecholamine response to a cycling sprint test (CST) in
      sedentary adolescent boys. METHODS: In this study, 31 adolescent boys (9 obese (%
      body fat = 31.0% +/- 3.0%), 11 overweight (% body fat = 24.0% +/- 1.6%), and 11
      lean (% body fat = 16.0% +/- 1.9%)), matched for peak oxygen consumption,
      completed a CST consisting of six 6-s maximal sprints with 2 min of passive rest
      between each repetition. Performance of each subject was determined as the mean
      power output (PO(mean)) developed during the CST. Plasma lactate, epinephrine,
      and norepinephrine concentrations were determined successively at rest, after a
      10-min warm-up, immediately after the CST, and after 20 min of passive recovery.
      RESULTS: Although groups were not different in age, height, or peak oxygen
      consumption (mL.kg(-1) fat-free mass.min(-1)), maximal epinephrine concentration
      was significantly (P < 0.05) higher in lean vs obese and was negatively
      correlated to body fat percentage (r = -0.60, P < 0.05). Maximal norepinephrine
      values were higher in lean versus overweight and obese, and a negative
      relationship was found between maximal norepinephrine concentration and body fat
      percentage (r = -0.60, P < 0.05). Maximal lactate concentration was higher in
      lean versus overweight and obese (14.7 +/- 3.3, 10.4 +/- 2.7, and 10.2 +/- 2.5 mM
      in lean, overweight, and obese, respectively). A significant relationship was
      also obtained between maximal norepinephrine and maximal epinephrine values with
      both maximal lactate concentration (r = 0.60 and r = 0.60, P < 0.05,
      respectively) and PO(mean) (r = 0.65 and r = 0.6, P < 0.05). CONCLUSIONS: Our
      results show that the catecholamine response to a CST was affected by body fat
      percentage, with reduced epinephrine and norepinephrine values in overweight and
      obese adolescents.

PMID- 20689463
TI  - Fast-start strategy improves VO2 kinetics and high-intensity exercise
      performance.
AB  - PURPOSE: The purpose of this study was to investigate the influence of pacing
      strategy on pulmonary VO2 kinetics and performance during high-intensity
      exercise. METHODS: Seven males completed 3- and 6-min bouts of cycle exercise on
      three occasions with the bouts initiated using an even-start (ES; constant work
      rate), fast-start (FS), or slow-start (SS) pacing strategy. In all conditions,
      subjects completed an all-out sprint over the final 60 s of the test as a measure
      of performance. RESULTS: For the 3-min exercise bouts, the mean response time
      (MRT) for the VO2 kinetics over the pacing phase was shortest in FS (35 +/- 6 s),
      longest in SS (55 +/- 14 s), and intermediate in ES (41 +/- 10 s) (P < 0.05 for
      all comparisons). For the 6-min bouts, the VO2 MRT was longer in SS (56 +/- 15 s)
      than that in FS and ES (38 +/- 7 and 42 +/- 6 s, respectively, P < 0.05). The VO2
      at the end of exercise was not different from the VO2max during the 6-min
      exercise bouts or 3-FS but was lower than VO2max for 3-ES and 3-SS (P < 0.05).
      The end-sprint performance was significantly enhanced in 3-FS compared with 3-ES
      and 3-SS (mean power = 374 +/- 68 vs 348 +/- 61 and 345 +/- 71 W, respectively; P
      < 0.05). However, end-sprint performance was unaffected by pacing strategy in the
      6-min bouts. CONCLUSIONS: These data indicate that an FS pacing strategy
      significantly improves performance during 3-min bouts of high-intensity exercise
      by speeding VO2 kinetics and enabling the attainment of VO2max.

PMID- 20689462
TI  - Predicting fat percent by skinfolds in racial groups: Durnin and Womersley
      revisited.
AB  - PURPOSE: Despite their widespread use in research and fitness settings, Durnin
      and Womersley's (DW) 1974 prediction equations using skinfold thickness to
      estimate body fat percent by hydrodensitometry have not been systematically
      evaluated in racial or ethnic groups using body fat percent measured by dual
      energy x-ray absorptiometry (%BF(DXA)) as the standard. METHODS: This cross
      sectional, population-based study examined whether the DW skinfold equations
      predict %BF(DXA) in a large, multiracial sample. Four skinfold measures (biceps,
      triceps, subscapular, and suprailiac), other clinical anthropometrics, and
      %BF(DXA) were obtained from 1675 healthy adults, age 18-110 yr, who were
      classified into four racial or ethnic categories: Caucasian, African American,
      Hispanic, or Asian. Predicted body fat percent using DW equations was compared
      with %BF(DXA) and evaluated within race/ethnicity- and sex-specific groups.
      RESULTS: Mean body fat percent predicted by DW equations was significantly
      different from %BF(DXA) in four of eight race/ethnicity- and sex-specific groups,
      particularly in Asian women and African American men (3.3 and 2.4 percentage
      point overestimates, respectively, P < 0.0001). New linear regression equations
      were developed estimating %BF(DXA) specific to each race/ethnicity and sex group,
      using the original DW skinfold sites. Body weight, height, and waist
      circumference independently predicted fat percent and were also included in the
      new equations. CONCLUSIONS: The 1974 DW equations did not predict %BF(DXA)
      uniformly in all races or ethnicities. Using %BF(DXA) as the criterion measure,
      the original DW skinfold equations have been updated specific to sex and
      race/ethnicity while maintaining the DW options for a minimalistic model using
      fewer predictors.

PMID- 20689464
TI  - Low-dose tibolone (1.25 mg/d) does not affect muscle strength in older women.
AB  - OBJECTIVE: More than 50% of all fractures occur in people without osteoporosis.
      Hormone therapy increases bone density, improves postural balance, and reduces
      fracture risk in postmenopausal women. It is unclear whether tibolone, a
      synthetic steroid hormone drug, can improve muscle strength. Thus, the aim of
      this study was to study the effects of low-dose tibolone therapy on muscle
      strength in older women. METHODS: Eighty healthy women (69 completed the study)
      60 years or older were recruited through advertising in the local media. They
      were randomly allocated to receive either tibolone 1.25 mg/day or placebo for 6
      months. The stand-up test was used to assess leg muscle strength and balance.
      Handgrip and leg muscle strength were measured using JAMAR and modified Cybex
      dynamometers. RESULTS: Baseline characteristics, including serum estradiol values
      and muscle strength, were similar in the two groups. Compliance with the therapy
      regimen was very high, averaging more than 97% in both groups. After 6 months,
      mean values for handgrip strength, knee extensor strength, and average time to
      perform 10 stands were improved numerically in both groups compared with values
      during baseline. However, there were no significant differences in these
      parameters within or between groups, and differences remained nonsignificant
      after adjustment for age, serum estradiol, and baseline value. CONCLUSIONS: Short
      term treatment with low-dose tibolone (1.25 mg/d) seems not to affect muscle
      strength in older women.

PMID- 20689465
TI  - Postmenopausal Evaluation and Risk Reduction With Lasofoxifene (PEARL) trial: 5
      year gynecological outcomes.
AB  - OBJECTIVE: The aim of this study was to establish the gynecological effects of 5
      years of treatment with lasofoxifene versus placebo in postmenopausal
      osteoporotic women. METHODS: A total of 8,556 women aged 59 to 80 years with
      femoral neck or spine bone mineral density T scores of -2.5 or lower were
      randomized to receive lasofoxifene 0.25 mg/day, or lasofoxifene 0.5 mg/day, or
      placebo, for 5 years. RESULTS: Endometrial cancer was confirmed for two women in
      each lasofoxifene group and for three women in the placebo group. Endometrial
      hyperplasia occurred in three, two, and zero women in the lasofoxifene 0.25
      mg/day, lasofoxifene 0.5 mg/day, and placebo groups, respectively. Vaginal
      bleeding occurred in 2.2% (P = 0.012 vs placebo), 2.6% (P = 0.001 vs placebo),
      and 1.3% of women treated with 0.25 mg/day lasofoxifene, 0.5 mg/day lasofoxifene,
      and placebo, respectively. Lasofoxifene treatment resulted in a small increase in
      endometrial thickness versus placebo (least-squares mean change from baseline
      1.19 mm [P = 0.001], 1.43 mm [P < 0.001], and -0.72 mm for 0.25 mg/day
      lasofoxifene, 0.5 mg/day lasofoxifene, and placebo). Similar numbers of women
      required surgery for pelvic organ prolapse or urinary incontinence in the placebo
      and 0.5 mg/day lasofoxifene groups (1.2% vs 1.6%, P = 0.224; 0.25 mg/day group:
      1.9%, P = 0.036). The absolute incidence rates of endometrial polyps were 8.8%,
      5.5%, and 3.3% for lasofoxifene 0.25 mg/day (P = 0.003 vs placebo), lasofoxifene
      0.5 mg/day (P = 0.163 vs placebo), and placebo groups, respectively. CONCLUSION:
      These findings indicate that 5 years of lasofoxifene treatment result in benign
      endometrial changes that do not increase the risk for endometrial cancer or
      hyperplasia in postmenopausal women.

PMID- 20689467
TI  - Improved quality of life, immunoglobulin G levels, and infection rates in
      patients with primary immunodeficiency diseases during self-treatment with
      subcutaneous immunoglobulin G.
AB  - OBJECTIVES: Primary immunodeficiency diseases (PIDDs) include a large class of
      genetically heterogeneous disorders which predispose patients to significant risk
      of serious and chronic/recurrent infections, as well as reduced quality of life
      (QoL). Intravenous immunoglobulin (IVIG) therapy improves the well being of PIDD
      patients; however, the need for venous access and potentially severe side effects
      frequently require administration in medical facilities. We evaluated the long
      term (12-month) experience with home-based self infusions of subcutaneous immune
      globulin (SCIG) in patients with PIDD on health-related QoL, rates of serious
      bacterial infections, and all other infections. METHODS: Adults (n = 42) and
      children (n = 9) with PIDD, previously treated with clinic-based IVIG, were
      trained to self administer SCIG at home. QoL (SF-36(R) and CHQ-PF50
      questionnaires), serious bacterial infections, serum immunoglobulin G (IgG)
      levels, overall infections, and incidence of adverse events were recorded at
      predetermined intervals. RESULTS: All patients had improved perceptions of
      general health (adults P = 0.047, children P = 0.037). Adults also had marked
      improvement in the bodily pain and vitality assessments, and parents had improved
      perceptions of personal and family activities. Serum IgG levels were maintained
      at mean levels 25% higher than previous troughs on IVIG. There were 162
      infections overall for an annual rate of 3.42/patient, but only 1 serious
      bacterial infection was observed (0.03/patient/yr). An average of 4.5 days/yr was
      missed from work or school per patient. CONCLUSIONS: Home SCIG therapy was safe
      and led to improved perceptions of general health, higher serum IgG levels, and
      very low rates of infections and days missed from work/school.

PMID- 20689466
TI  - Effect of hormone therapy on lean body mass, falls, and fractures: 6-year results
      from the Women's Health Initiative hormone trials.
AB  - OBJECTIVE: Loss of lean body mass with aging may contribute to falls and
      fractures. The objective of this analysis was to determine if taking
      postmenopausal hormone therapy (or HT: estrogen plus progestogen therapy or
      estrogen therapy alone) favorably affects age-related changes in lean body mass
      and if these changes partially account for decreased falls or fractures with HT.
      METHODS: Participants randomly assigned to either estrogen plus progestogen
      therapy (n = 543) or control (n = 471) and estrogen therapy alone (n = 453) or
      control (n = 474) and receiving dual-energy x-ray absorptiometry scans to
      estimate body composition during the Women's Health Initiative were evaluated.
      Falls and fracture occurrence were obtained by annual self-report. Fractures were
      confirmed by a clinical chart review. RESULTS: At 6 years postrandomization, lean
      body mass was not different between HT and control groups. Although lean body
      mass positively influenced bone mineral density, independent of HT status, the
      preserved lean body mass observed in the HT arms in the first 3 years did not
      significantly contribute to models evaluating HT influence on falls and fractures
      between years 3 and 6. Women taking at least 80% of their medication in the HT
      arms demonstrated fewer falls compared with placebo; this difference was not
      attributable to change in lean body mass. CONCLUSIONS: Despite early preservation
      of lean body mass with HT (3 y), HT did not ameliorate long-term (6 y) loss in
      lean body mass with aging.

PMID- 20689468
TI  - Myocarditis masquerading as a ST elevation myocardial infarction (STEMI).
AB  - Myocarditis is an inflammatory disease of the myocardium with a wide range of
      clinical presentations, from vague flu-like symptoms to rapidly progressive heart
      failure. The diagnosis is made histopathologically, with the help of
      immunohistochemical stains. Myocarditis is classified by specific criteria, and
      the myocardial biopsy reveals an inflammatory infiltrate with necrosis and/or
      degeneration of adjacent myocytes. The case of a young woman who presented with a
      ST elevation myocardial infarction (STEMI) is presented. The current literature
      is reviewed to discuss the approach to evaluation and treatment of suspected
      myocarditis.

PMID- 20689469
TI  - A rare cause of wheezing.

PMID- 20689470
TI  - Successful endoscopic clip closure of postoperative esophageal leak.

PMID- 20689471
TI  - Carotid artery puncture, myocardial injury, and ventricular arrhythmia.

PMID- 20689472
TI  - A case of an unusual foreign body of the tongue.

PMID- 20689473
TI  - Alanine aminotransferase concentrations in elite athletes.

PMID- 20689474
TI  - Subcutaneous hydatid cyst of the thigh.

PMID- 20689475
TI  - Case of reverse takotsubo cardiomyopathy in status asthmaticus.

PMID- 20689476
TI  - Scedosporium apiospermum infection presenting as a pneumothorax and cavitary lung
      lesions in a patient with acquired immune deficiency syndrome.
AB  - The Scedosporium genus consists of filamentous fungi that inhabit soil, sewage,
      manure, and polluted waters, and contains two medically important species:
      Scedosporium apiospermum and Scedosporium prolificans. Scedosporiosis is caused
      by inhalation or traumatic subcutaneous implantation of the organism, and may
      have varied clinical presentations. A variety of pulmonary manifestations can
      occur, but to our knowledge, pneumothorax as initial presentation has not been
      reported. Treatment may be difficult, as the disease occurs more commonly in
      immunocompromised patients, and the organism may demonstrate resistance to
      various antifungal agents. We describe successful treatment of extensive
      pulmonary disease due to S apiospermum in a patient with acquired immune
      deficiency syndrome (AIDS).

PMID- 20689477
TI  - Cerebrospinal fluid viscosity: a novel diagnostic measure for acute meningitis.
AB  - INTRODUCTION: Early diagnosis of acute meningitis has paramount importance in
      clinical practice because of mortality and morbidity of the disease. Examination
      of cerebrospinal fluid (CSF) has critical value for the diagnosis of acute
      meningitis and discrimination of bacterial and aseptic meningitis. It has been
      previously reported that plasma viscosity can be used as an inflammatory marker.
      In this study we aimed to evaluate the role of CSF viscosity as a complementary
      measure for diagnosis of meningitis in suspected patients. METHODS: Forty-one
      consecutive patients who underwent lumbar puncture to rule out meningitis were
      studied prospectively. Twenty-seven patients were diagnosed with meningitis, of
      whom 13 patients had aseptic meningitis and 14 patients had bacterial meningitis.
      Meningitis was ruled out in 14 patients. RESULTS: CSF protein and CSF viscosity
      were significantly higher in patients with meningitis compared to nonmeningitis.
      Receiver operator characteristic (ROC) analysis revealed that CSF viscosity was
      highly sensitive (100%) and specific (93%); measures for the diagnosis of
      meningitis in the study population was comparable to those of CSF protein.
      Additionally, patients with meningitis were also divided into two groups as
      having bacterial and aseptic meningitis. CSF viscosity also significantly
      differed between bacterial and aseptic meningitis. CONCLUSION: The CSF viscosity
      is a simple and easy method and can be used as an adjunctive measure for the
      diagnosis of meningitis. With the support of further and larger clinical studies,
      CSF viscosity may have a role in the discrimination of bacterial versus aseptic
      meningitis.

PMID- 20689478
TI  - Types of hair loss and treatment options, including the novel low-level light
      therapy and its proposed mechanism.
AB  - Androgenetic alopecia (AGA) is the most common form of hair loss in men, and
      female pattern hair loss (FPHL) is the most common form of hair loss in women.
      Traditional methods of treating hair loss have included minoxidil, finasteride,
      and surgical transplantation. Currently there is a myriad of new and experimental
      treatments. In addition, low-level light therapy (LLLT) has recently been
      approved by the United States Food and Drug Administration (FDA) for the
      treatment of hair loss. There are several theories and minimal clinical evidence
      of the safety and efficacy of LLLT, although most experts agree that it is safe.
      More in vitro studies are necessary to elucidate the mechanism and effectiveness
      at the cellular level, and more controlled studies are necessary to assess the
      role of this new treatment in the general population.

PMID- 20689479
TI  - Invasive cancer in a diminutive rectal polyp amidst internal hemorrhoids detected
      by rectal retroflexion.
AB  - A diminutive rectal polyp amidst internal hemorrhoids, detected by rectal
      retroflexion during colonoscopy, was shown to harbor invasive rectal
      adenocarcinoma by colonoscopic biopsy. Initially this lesion had appeared to be a
      relatively innocuous prominent anorectal mucosal fold and was recognized as a
      diminutive polyp only after careful rectal retroflexion during colonoscopy. This
      report emphasizes that lesions just above the anorectal junction with atypical
      endoscopic features for internal hemorrhoids should be carefully examined at
      rectal retroflexion and that polyps or suspicious lesions amidst internal
      hemorrhoids identified during colonoscopy should be snared or at least biopsied,
      even if small. This case report also illustrates how easily an early cancer in a
      diminutive colonic polyp can be missed when in difficult areas of colonoscopic
      inspection, such as behind a colonic fold or immediately above the anus.

PMID- 20689480
TI  - Bordetella bronchiseptica bacteremia in a patient with AIDS.
AB  - Bordetella bronchiseptica bacteremia is often associated with various infection
      in animals. The majority of B bronchiseptica infections reported in humans are
      cases of pneumonia. Very few cases have been reported in patients with a history
      of acquired immune deficiency syndrome (AIDS). The patient described herein, who
      had a history of AIDS, was likely infected with B bronchiseptica as a result of
      his hemodialysis catheter. The patient was successfully treated with antibiotics
      without the removal of the catheter.

PMID- 20689481
TI  - Clinical manifestations, radiographic findings, treatment options, and outcome in
      sarcoidosis patients with upper respiratory tract involvement.
AB  - BACKGROUND: Sarcoidosis of the upper respiratory tract (SURT) is an
      underappreciated manifestation of sarcoidosis. We described the
      clinicoradiological findings, methods of treatment, and outcomes of 68 patients
      with SURT seen in our clinic over a 7-year period. METHODS: This was a
      retrospective study. A Case Control Etiology of Sarcoidosis Study (ACCESS)
      instrument of organ involvement was used to classify patients with SURT. Patients
      with a definite or probable diagnosis of SURT underwent chart review for
      symptoms, radiological features, treatment, and outcome. RESULTS: There were 6.8%
      (68/998) of patients in the sarcoidosis clinic who had SURT. The most common
      presenting symptom was nasal congestion (61%, 34/56). In patients who had SURT
      diagnosed after the initial presentation of sarcoidosis, the mean prednisone dose
      more than quadrupled (4 + or - 6.5 vs 18.6 + or - 15.9, P = 0.002) between the
      diagnosis of SURT and the end of follow up. By the end of follow up, only 40% of
      our cohort had significant improvement of SURT. CONCLUSION: SURT is a form of
      sarcoidosis that is not uncommon. Relatively high doses of corticosteroids are
      required to control the disease, and improvement occurs in a minority of the
      patients although the disease usually can be stabilized. Surgery should be
      reserved for life-threatening complications as surgical outcomes are relatively
      poor.

PMID- 20689482
TI  - Panniculitis ossificans in a patient with excessive push-ups: imaging findings
      with histological correlation.
AB  - Panniculitis ossificans arising symmetrically in the subcutaneous layer of both
      shoulders is rare. A case of a 27-year-old man with recent history of doing
      excessive push-ups is reported. According to the patient's statement, there is no
      notable history of alcoholism, major trauma, or injection of nonsteroidal anti
      inflammatory drugs. Computed tomography of both shoulders showed multiple
      subcutaneous masses with calcified/ossified rims and central fatty content.
      Histological examination confirmed the diagnosis of panniculitis ossificans,
      showing subcutaneous fat necrosis associated with osteoid material.

PMID- 20689483
TI  - Public health response to a multidrug-resistant tuberculosis outbreak among
      Guatemalans in Tennessee, 2007.
AB  - BACKGROUND: In June 2007, the Tennessee Department of Health notified the Centers
      for Disease Control and Prevention of four multidrug-resistant tuberculosis (MDR
      TB) cases in individuals of Guatemalan descent, and requested onsite
      epidemiologic assistance to investigate this outbreak. METHODS: A case was
      defined as either culture-confirmed MDR TB with a drug-susceptibility pattern
      closely resembling that of the index case, or a clinical diagnosis of active TB
      disease and corroborated contact with a person with culture-confirmed MDR TB.
      Medical records were reviewed, and patients and their contacts were interviewed.
      RESULTS: Five secondary TB cases were associated with the index case. Of 369
      contacts of the index case, 189 (51%) were evaluated. Of those, 97 (51%) had
      positive tuberculin skin test (TST) results, 79 (81%) began therapy for latent TB
      infection (LTBI), and 38 (48%) completed LTBI therapy. CONCLUSION: Despite
      consistent follow up by public health officials, a low proportion of patients
      diagnosed with LTBI completed therapy. Clinicians and public health practitioners
      who serve immigrant communities should be vigilant for MDR TB.

PMID- 20689484
TI  - Change in bilirubin level following acute myocardial infarction is an index for
      heme oxygenase activation.
AB  - OBJECTIVES: Heme oxygenase 1 (HO-1) is rapidly induced by stress, degrading pro
      oxidant heme into carbon monoxide, bilirubin, and free iron (Fe). Induction of HO
      1 is an important defense mechanism against tissue injury. Here, we tested the
      hypothesis that HO-1 is activated in the myocardium after acute myocardial
      infarction (AMI) in humans. METHODS: Changes in the HO-1 activity after AMI were
      analyzed by measuring serum levels of bilirubin and Fe. Blood samples were
      collected in patients with AMI (n = 41) serially after the interventional therapy
      and compared with non-AMI subjects (n = 18). HO-1 protein levels were measured in
      a sample of AMI patients (n = 12). RESULTS: In AMI patients, but not in non-AMI
      subjects, serum levels of bilirubin (1.57 fold, P < 0.001) and Fe (1.35 fold, P <
      0.01) were transiently elevated, both levels peaking 18-21 hours after the start
      of sampling. The peak changes in the levels of bilirubin and Fe in AMI patients
      were significantly correlated with each other. Furthermore, the serum HO-1
      protein level was elevated, and its change was significantly correlated with the
      change in bilirubin level (r = 0.82, P < 0.005). Those with a high bilirubin
      response (peak levels >0.5 mg/dL) had richer collateral flow into the ischemic
      myocardium. CONCLUSIONS: These results suggest that heme oxygenase (HO) was
      activated following AMI, and it was detectable in the serum. Our data provide the
      first evidence of HO-1 induction following stress in humans. The change in
      bilirubin level may be a novel index for high collateral flow formation following
      AMI.

PMID- 20689485
TI  - Hemoptysis requiring bronchial artery embolization in pulmonary arterial
      hypertension.
AB  - OBJECTIVES: Hemoptysis is an uncommon complication in patients with pulmonary
      arterial hypertension (PAH). Although the mechanism of hemoptysis is unknown,
      treatment with bronchial artery embolization (BAE) is proposed to be a safe and
      reliable method of treatment. We report our experience in treating PAH patients
      presenting with acute hemoptysis that required multiple BAEs. METHODS: Three
      female and one male PAH patients, ages 45 + or - 9 years (mean + or - standard
      deviation [SD]) presented with acute hemoptysis. Right ventricular systolic
      pressure and cardiac index at the time of the first episode of hemoptysis were 85
      + or - 17 mm Hg and 2.7 + or - 0.7 L/min/m, respectively. Two of the four
      patients had recurrent episodes of hemoptysis, requiring multiple BAEs. All four
      were on intravenous prostacyclin analogue. None were receiving warfarin or
      endothelin receptor antagonists at the time of the episode. During each episode
      of hemoptysis, international normalized ratio (INR) was 1.09 + or - 0.11 units,
      and platelet count was 124,000 + or - 47,000 per microliter. RESULTS: Each
      episode of hemoptysis was acutely terminated with BAE. In the majority of cases,
      patients had multiple aberrant bronchial arteries embolized, and an average of
      2.3 arteries was embolized per session (1-4 embolized arteries). Each BAE was
      performed utilizing polyvinyl alcohol particles, ranging from 250-500 microns.
      There were no reported complications of the 14 BAE procedures performed.
      CONCLUSION: Although the incidence of hemoptysis is unknown and likely
      underreported, we report our experience in which recurrent hemoptysis was treated
      with multiple BAE procedures. This report emphasizes the efficacy and safety of
      BAE in terminating episodes of recurrent hemoptysis in patients with severe PAH.

PMID- 20689486
TI  - Type 2 diabetes mellitus: managing hemoglobin A(1c) and beyond.
AB  - Comprehensive glycemic control, as demonstrated by desirable glycated hemoglobin
      A1c (HbA1c), postprandial glucose (PPG), and fasting plasma glucose (FPG) levels,
      is imperative for managing patients with type 2 diabetes mellitus (T2DM). It is
      important to minimize fluctuations in blood glucose levels, as they are thought
      to contribute to both the microvascular and macrovascular complications. The
      HbA1c measurement itself is not always indicative of the magnitude or frequency
      of glucose fluctuations during the course of a day. Therefore, treatment should
      be aimed at reducing not only HbA1c, but also PPG and FPG in order to achieve
      glycemic control. At the same time, patient safety should be a priority. Glycemic
      control also means minimizing hypoglycemic episodes, which elevate the risk for
      additional complications. In addition to being life-threatening, hypoglycemia may
      cause hypoglycemia unawareness and compromised counterregulatory mechanisms. It
      may also lead to serious short- and long-term effects, including cognitive
      impairment and dementia. As most patients are unable to maintain glycemic control
      on monotherapy, fortunately, effective combination regimens are available with
      agents having complementary mechanisms that act upon HbA1c, PPG, and FPG with
      minimal risk of hypoglycemia or weight gain.

PMID- 20689487
TI  - Mucosa-associated lymphoma tissue of the dura presenting as meningioma.
AB  - Mucosa-associated lymphoma tissue (MALT) of the dura is extremely rare, with only
      a few reported cases worldwide. We present a unique case of a 61-year-old female
      who presented with neurologic symptoms of unsteady gait, dizziness, and sharp
      pain on her scalp for 3 weeks. A subsequent magnetic resonance imaging (MRI) of
      the brain demonstrated a dural-based mass radiographically consistent with
      meningioma. However, biopsy revealed the cells to be immunopositive for CD20 and
      CD79a, and immunonegative for CD5, CD10, CD43, and CD23. The neoplastic small
      lymphoid B cells were MUM1 positive and showed kappa light chain restriction,
      consistent with MALT of the dura. No evidence of systemic disease was found. The
      patient underwent radiation, which resulted in a complete response. MALT
      lymphoma, while rare, must be considered in the differential diagnosis in
      patients presenting radiographically with meningioma.

PMID- 20689488
TI  - Consideration of subcutaneous immunoglobulin replacement therapy in humoral
      immunodeficiency patients.

PMID- 20689489
TI  - Urinothorax: presentation of a new case as pleural exudate.
AB  - Urinothorax or urothorax (UT) is a rare condition which often goes undiagnosed.
      In published cases of UT, the pleural fluid is usually transudative and is very
      rarely exudative. We present a case of UT after right nephroureterectomy for
      urothelial carcinoma, in which the pleural fluid presented characteristics of
      exudate. The diagnosis of UT was confirmed with the finding of a pleural/serum
      creatinine ratio above one and after demonstrating the presence of a postsurgical
      urinoma in the right renal fossa. UT should be included in the differential
      diagnosis of pleural effusion in patients with a recent urinary tract disorder,
      even when it is pleural exudate.

PMID- 20689490
TI  - Cervical myelopathy from spinal sarcoidosis as the unexpected initial
      presentation for systemic sarcoidosis.
AB  - This is a case which highlights unique diagnostic challenges in the evaluation of
      a previously healthy patient presenting with a myelopathy initially most
      concerning for malignancy. However, timely recognition and nonoperative therapy
      of unexpected spinal sarcoidosis with corticosteroidal therapy was crucial in
      averting the sequelae of undiagnosed or misdiagnosed neurosarcoidosis, which can
      be devastating and life-threatening. Diagnosis is challenging due to significant
      similarities in clinical and roentgenographic findings of spinal sarcoidosis with
      infection, inflammation, and malignancy. Our case demonstrates that diagnosis of
      spinal sarcoidosis is especially elusive when it is the initial manifestation of
      sarcoidosis.

PMID- 20689491
TI  - Amiodarone and thyroid dysfunction.
AB  - Amiodarone is a potent antiarrhythmic drug associated with thyroid dysfunction.
      Its high iodine content causes inhibition of 5'-deiodinase activity. Most
      patients remain euthyroid. Amiodarone-induced thyrotoxicosis (AIT) or amiodarone
      induced hypothyroidism (AIH) may occur depending on the iodine status of
      individuals and prior thyroid disease. AIT is caused by excess iodine-induced
      thyroid hormone synthesis (type I AIT) or by destructive thyroiditis (type II
      AIT). If the medical condition allows it, discontinuation of the drug is
      recommended in type I AIT. Otherwise, large doses of thioamides are required.
      Type II AIT is treated with corticosteroids. Mixed cases require a combination of
      both drugs. Potassium perchlorate has been used to treat resistant cases of type
      I AIT but use is limited by toxicity. Thyroidectomy, plasmapheresis, lithium, and
      radioiodine are used in select cases of AIT. AIH is successfully treated with
      levothyroxine. Screening for thyroid disease before starting amiodarone and
      periodic monitoring of thyroid function tests are advocated.

PMID- 20689492
TI  - Goals for HbA1c need to be individualized based on clinical judgment, instead of
      third party recommendations.

PMID- 20689493
TI  - Proximal intercessory prayer.

PMID- 20689494
TI  - Acute pylephlebitis following gastrointestinal infection: an unrecognized cause
      of septic shock.
AB  - Pylephlebitis is the septic thrombosis of the portal vein. Hypercoagulability and
      intra-abdominal sepsis are the main predisposing factors. A 25-year-old man
      presented to a primary health care center complaining of fever, epigastric pain,
      and jaundice. He was initially diagnosed with a gastrointestinal infection and
      alcoholic hepatitis and, due to his unstable clinical status, was referred to the
      emergency room. A diagnosis of acute pylephlebitis complicated with septic shock
      was made. Treatment with a wide-spectrum antibiotic and anticoagulation was
      initiated. Fifteen days later, recanalization of the portal vein was achieved and
      clinical status was improved. Pylephlebitis following gastrointestinal infection
      is a potential cause of septic shock.

PMID- 20689495
TI  - A one year prospective comparison of kidney growth and function in children
      recipients of grafts from children and adults.
AB  - BACKGROUND: Renal grafts have demonstrated capacity to adapt to the recipient.
      The aim of this study was to assess the growth of renal grafts transplanted to
      children, during the first year posttransplant. METHODS: We conducted a 1 year
      prospective study comparing the growth of renal grafts from children and adults
      donors transplanted in children, and correlated this growth with graft function.
      Two groups were studied: (a) group 1-32 children transplanted with pediatric
      deceased kidneys from donors younger than 16 years and (b) group 2-31 children
      transplanted with organs from adult living donors. Anthropometric assessment,
      sonographic measurement of the graft, and serum creatinine at 1 week, 1, 6, and
      12 months posttransplantation were performed. RESULTS: Children from group 1
      presented an 18% increase in graft volume after the sixth month of transplant,
      whereas in group 2 grafts presented a 14% reduction in volume, mainly during the
      first month; the variation in renal diameters was not uniform. Children from
      group 1 presented a glomerular filtration rate (GFR) increase during the follow
      up (46-102 mL/min/1.73 m). After 1 year, GFR and graft volume were similar.
      Growth of individuals from both groups was comparable. CONCLUSIONS: In the short
      term, pediatric kidneys raise volume and GFR, whereas adult kidneys slightly
      lower volume and GFR when transplanted in children. Taking our and other studies
      results into consideration, we can hypothesize that in addition to compensatory
      hypertrophy, pediatric grafts are likely capable of continued somatic growth.

PMID- 20689496
TI  - Reduced ischemia-reoxygenation injury in rat intestine after luminal preservation
      with a tailored solution.
AB  - BACKGROUND: The intestine is extremely sensitive to ischemic preservation and
      reoxygenation injury. Current vascular perfusion and cold storage with University
      of Wisconsin (UW) solution neglect the intestinal lumen and the ongoing mucosal
      metabolism during hypothermia. This study was designed to test the effects of
      luminal preservation with an alternative preservation solution in addition to the
      common vascular flush with UW solution on graft viability after preservation and
      ex vivo reoxygenation. METHODS: Rat intestine was preserved on ice for 6 hr in UW
      solution or Williams Medium E with additional buffering, impermeants, and a
      colloid (WMEplus) after being stapled or after flushing and filling the lumen
      with the respective preservation solution. Tissue slices were prepared from fresh
      and preserved intestines and were incubated with oxygen for 6 hr at 37 degrees C
      to assess the viability after reoxygenation. RESULTS: Directly after
      preservation, histologic damage was mild and unaffected by preservation strategy.
      Contrary to luminal preservation, closed preservation resulted in significantly
      decreased ATP levels compared with control. Reoxygenation aggravated damage and
      revealed differences between the strategies. Luminal preservation better
      maintained the ATP levels and histologic integrity (vs. closed preservation) for
      both solutions. Histomorphologic integrity was superior after preservation with
      WMEplus (vs. UW solution). Expression of stress responsive genes was least up
      regulated in the slices from tissue preserved luminally with WMEplus.
      CONCLUSIONS: In conclusion, preservation and reoxygenation injury can be
      attenuated by luminal preservation with WMEplus.

PMID- 20689497
TI  - Launching a National Surveillance System after an earthquake --- Haiti, 2010.
AB  - On January 12, 2010, Haiti experienced a magnitude-7.0 earthquake; Haitian
      government officials estimated that 230,000 persons died and 300,000 were
      injured. At the time, Haiti had no system capable of providing timely
      surveillance on a wide range of health conditions. Within 2 weeks, Haiti's
      Ministry of Public Health and Population (MSPP), the Pan-American Health
      Organization (PAHO), CDC, and other national and international agencies launched
      the National Sentinel Site Surveillance (NSSS) System. The objectives were to
      monitor disease trends, detect outbreaks, and characterize the affected
      population to target relief efforts. Fifty-one hospital and clinic surveillance
      sites affiliated with the U.S. President's Emergency Plan for AIDS Relief
      (PEPFAR) were selected to report daily counts by e-mail or telephone for 25
      specified reportable conditions. During January 25-April 24, 2010, a total of
      42,361 persons had a reportable condition; of these, 54.5% were female, and 32.6%
      were aged <5 years. Nationally, the three most frequently reported specified
      conditions were acute respiratory infection (ARI) (16.3%), suspected malaria
      (10.3%), and fever of unknown cause (10.0%). Injuries accounted for 12.0% of
      reported conditions. No epidemics or disease clusters were detected. The number
      of reports decreased over time. NSSS is ongoing and currently transitioning into
      becoming a long-term national surveillance system for Haiti. NSSS data could
      assist decision makers in allocation of resources and identifying effective
      public health interventions. However, data reporting and quality could be
      improved by additional surveillance education for health-care providers,
      laboratory confirmation of cases of disease, and Internet-based weekly reporting.

PMID- 20689498
TI  - Rapid establishment of an internally displaced persons disease surveillance
      system after an earthquake --- Haiti, 2010.
AB  - On January 12, 2010, a 7.0-magnitude earthquake in Haiti disrupted infrastructure
      and displaced approximately 2 million persons, causing increased risk for
      communicable diseases from overcrowding and poor living conditions. Hundreds of
      nongovernmental organizations (NGOs) established health-care clinics in camps of
      internally displaced persons (IDPs). To monitor conditions of outbreak potential
      identified at NGO camp clinics, on February 18, the Haiti Ministry of Public
      Health and Population (MSPP), the Pan-American Health Organization (PAHO), and
      CDC implemented the IDP Surveillance System (IDPSS). The Inter-Agency Standing
      Committee (IASC) "cluster approach" was used to coordinate the Haiti humanitarian
      response. One of 11 clusters, the Global Health Cluster (GHC), builds global
      capacity, whereas the country-level cluster (in this case, the Haitian Health
      Cluster [HHC], led by PAHO) responds locally. During the Haiti response, HHC
      engaged NGOs serving large camps, established IDPSS, followed trends of
      reportable conditions, undertook epidemiologic and laboratory investigations, and
      fostered implementation of control measures. This report describes the design and
      implementation of IDPSS in the post-earthquake period. The primary challenges to
      implementing IDPSS were communication difficulties with an ever-changing group of
      NGO partners and limitations to the utility of IDPSS data because of lack of
      reliable camp population denominator estimates. The IDPSS experience reinforces
      the need to improve local communication and coordination strategies. Improving
      future humanitarian response requires advance development and distribution of
      easily adaptable standard surveillance tools, development of an interdisciplinary
      strategy for an early and reliable population census, and development of
      communication strategies using locally available Internet and cellular networks.

PMID- 20689499
TI  - Any tobacco use in 13 States --- behavioral risk factor surveillance system,
      2008.
AB  - Tobacco use is the leading cause of preventable death in the United States, and
      cigarette smoking, the predominant form of tobacco use in the United States,
      causes 443,000 deaths annually. In 2008, 20.6% of U.S. adults were current
      smokers; however, other tobacco products (e.g., smokeless tobacco, cigars, bidis,
      and kreteks) also were used by some adults and youths. Persons who use cigarettes
      in combination with other tobacco products (polytobacco use) might have an in
      increased risk for adverse health effects. To estimate the prevalence of any
      tobacco and polytobacco use, CDC analyzed data from the 2008 Behavioral Risk
      Factor Surveillance System (BRFSS) (the most recent data available) module on use
      of other tobacco products, which was implemented by 13 states. This analysis
      found that use of any tobacco product ranged from 18.4% (New Jersey) to 35.0%
      (West Virginia), cigarette use ranged from 14.6% (New Jersey) to 26.6% (West
      Virginia), and polytobacco use ranged from 1.0% (New Jersey) to 3.7% (West
      Virginia). Polytobacco use was more prevalent among men (4.4%), persons aged 18-
      24 years (5.7%), persons who were single (4.8%), persons with household incomes
      less than $35,000 (9.8%), and persons with less than a high school education
      (3.6%) or with a high school diploma or General Education Development (GED)
      certificate or diploma (3.6%). Because no form of tobacco is safe to use,
      prevention and cessation intervention programs need to address all forms of
      tobacco use to lower tobacco-related morbidity and mortality in the United
      States. Additionally, counter-marketing messages for tobacco products can be
      tailored for specific populations, such as young adults and males.

PMID- 20689500
TI  - Vital signs: state-specific obesity prevalence among adults --- United States,
      2009.
AB  - BACKGROUND: Obesity is a costly condition that can reduce quality of life and
      increases the risk for many serious chronic diseases and premature death. The
      U.S. Surgeon General issued the Call to Action to Prevent and Decrease Overweight
      and Obesity in 2001, and in 2007, no state had met the Healthy People 2010
      objective to reduce obesity prevalence among adults to 15%. METHODS: CDC used
      2009 Behavioral Risk Factor Surveillance System survey data to update estimates
      of national and state-specific obesity prevalence. Obesity was calculated based
      on self-reported weight and height and defined as body mass index (weight [kg] /
      height [m]2) >or=30. RESULTS: Overall self-reported obesity prevalence in the
      United States was 26.7%. Non-Hispanic blacks (36.8%), Hispanics (30.7%), those
      who did not graduate from high school (32.9%), and persons aged 50-59 years
      (31.1%) and 60-69 years (30.9%) were disproportionally affected. By state,
      obesity prevalence ranged from 18.6% in Colorado to 34.4% in Mississippi; only
      Colorado and the District of Columbia (19.7%) had prevalences of <20%; nine
      states had prevalences of >or=30%. CONCLUSIONS: In 2009, no state met the Healthy
      People 2010 obesity target of 15%, and the self-reported overall prevalence of
      obesity among U.S. adults had increased 1.1 percentage points from 2007.
      IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Obesity should be addressed through a
      comprehensive approach across multiple settings and sectors that can change
      individual nutrition and physical activity behaviors and the environments and
      policies that affect these behaviors. New and continued national, state, and
      community-level surveillance of obesity, its behavioral risk factors, and the
      environments and policies that affect these behaviors is critical to monitor
      progress in obesity prevention and to target interventions.

PMID- 20689501
TI  - Prevention and control of influenza with vaccines: recommendations of the
      Advisory Committee on Immunization Practices (ACIP), 2010.
AB  - This report updates the 2009 recommendations by CDC's Advisory Committee on
      Immunization Practices (ACIP) regarding the use of influenza vaccine for the
      prevention and control of influenza (CDC. Prevention and control of influenza:
      recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR
      2009;58[No. RR-8] and CDC. Use of influenza A (H1N1) 2009 monovalent vaccine--
      recommendations of the Advisory Committee on Immunization Practices [ACIP], 2009.
      MMWR 2009;58:[No. RR-10]). The 2010 influenza recommendations include new and
      updated information. Highlights of the 2010 recommendations include 1) a
      recommendation that annual vaccination be administered to all persons aged >or=6
      months for the 2010-11 influenza season; 2) a recommendation that children aged 6
      months--8 years whose vaccination status is unknown or who have never received
      seasonal influenza vaccine before (or who received seasonal vaccine for the first
      time in 2009-10 but received only 1 dose in their first year of vaccination) as
      well as children who did not receive at least 1 dose of an influenza A (H1N1)
      2009 monovalent vaccine regardless of previous influenza vaccine history should
      receive 2 doses of a 2010-11 seasonal influenza vaccine (minimum interval: 4
      weeks) during the 2010--11 season; 3) a recommendation that vaccines containing
      the 2010-11 trivalent vaccine virus strains A/California/7/2009 (H1N1)-like (the
      same strain as was used for 2009 H1N1 monovalent vaccines), A/Perth/16/2009
      (H3N2)-like, and B/Brisbane/60/2008-like antigens be used; 4) information about
      Fluzone High-Dose, a newly approved vaccine for persons aged >or=65 years; and 5)
      information about other standard-dose newly approved influenza vaccines and
      previously approved vaccines with expanded age indications. Vaccination efforts
      should begin as soon as the 2010-11 seasonal influenza vaccine is available and
      continue through the influenza season. These recommendations also include a
      summary of safety data for U.S.-licensed influenza vaccines. These
      recommendations and other information are available at CDC's influenza website
      (http://www.cdc.gov/flu); any updates or supplements that might be required
      during the 2010-11 influenza season also will be available at this website.
      Recommendations for influenza diagnosis and antiviral use will be published
      before the start of the 2010-11 influenza season. Vaccination and health-care
      providers should be alert to announcements of recommendation updates and should
      check the CDC influenza website periodically for additional information.

PMID- 20689502
TI  - Murine bioluminescent hepatic tumour model.
AB  - This video describes the establishment of liver metastases in a mouse model that
      can be subsequently analysed by bioluminescent imaging. Tumour cells are
      administered specifically to the liver to induce a localised liver tumour, via
      mobilisation of the spleen and splitting into two, leaving intact the vascular
      pedicle for each half of the spleen. Lewis lung carcinoma cells that
      constitutively express the firefly luciferase gene (luc1) are inoculated into one
      hemi-spleen which is then resected 10 minutes later. The other hemi-spleen is
      left intact and returned to the abdomen. Liver tumour growth can be monitored by
      bioluminescence imaging using the IVIS whole body imaging system. Quantitative
      imaging of tumour growth using IVIS provides precise quantitation of viable
      tumour cells. Tumour cell death and necrosis due to drug treatment is indicated
      early by a reduction in the bioluminescent signal. This mouse model allows for
      investigating the mechanisms underlying metastatic tumour-cell survival and
      growth and can be used for the evaluation of therapeutics of liver metastasis.

PMID- 20689503
TI  - Dissection of oenocytes from adult Drosophila melanogaster.
AB  - In Drosophila melanogaster, as in other insects, a waxy layer on the outer
      surface of the cuticle, composed primarily of hydrocarbon compounds, provides
      protection against desiccation and other environmental challenges. Several of
      these cuticular hydrocarbon (CHC) compounds also function as semiochemical
      signals, and as such mediate pheromonal communications between members of the
      same species, or in some instances between different species, and influence
      behavior. Specialized cells referred to as oenocytes are regarded as the primary
      site for CHC synthesis. However, relatively little is known regarding the
      involvement of the oenocytes in the regulation of the biosynthetic, transport,
      and deposition pathways contributing to CHC output. Given the significant role
      that CHCs play in several aspects of insect biology, including chemical
      communication, desiccation resistance, and immunity, it is important to gain a
      greater understanding of the molecular and genetic regulation of CHC production
      within these specialized cells. The adult oenocytes of D. melanogaster are
      located within the abdominal integument, and are metamerically arrayed in ribbon
      like clusters radiating along the inner cuticular surface of each abdominal
      segment. In this video article we demonstrate a dissection technique used for the
      preparation of oenocytes from adult D. melanogaster. Specifically, we provide a
      detailed step-by-step demonstration of (1) how to fillet prepare an adult
      Drosophila abdomen, (2) how to identify the oenocytes and discern them from other
      tissues, and (3) how to remove intact oenocyte clusters from the abdominal
      integument. A brief experimental illustration of how this preparation can be used
      to examine the expression of genes involved in hydrocarbon synthesis is included.
      The dissected preparation demonstrated herein will allow for the detailed
      molecular and genetic analysis of oenocyte function in the adult fruit fly.

PMID- 20689504
TI  - Transplantation of GFP-expressing blastomeres for live imaging of retinal and
      brain development in chimeric zebrafish embryos.
AB  - Cells change extensively in their locations and property during embryogenesis.
      These changes are regulated by the interactions between the cells and their
      environment. Chimeric embryos, which are composed of cells of different genetic
      background, are great tools to study the cell-cell interactions mediated by genes
      of interest. The embryonic transparency of zebrafish at early developmental
      stages permits direct visualization of the morphogenesis of tissues and organs at
      the cellular level. Here, we demonstrate a protocol to generate chimeric retinas
      and brains in zebrafish embryos and to perform live imaging of the donor cells.
      The protocol covers the preparation of transplantation needles, the
      transplantation of GFP-expressing donor blastomeres to GFP-negative hosts, and
      the examination of donor cell behavior under live confocal microscopy. With
      slight modifications, this protocol can also be used to study the embryonic
      development of other tissues and organs in zebrafish. The advantages of using GFP
      to label donor cells are also discussed.

PMID- 20689505
TI  - Preparation of mouse brain tissue for immunoelectron microscopy.
AB  - Transmission electron microscopy (TEM) is extremely useful for visualizing
      microglial, oligodendrocytic, astrocytic, and neuronal subcellular compartments
      (dendrite, dendritic spine, axon, axon terminal, perikaryon), as well as their
      intracellular organelles and cytoskeleton, in the central nervous system at high
      spatial resolution. Combined with TEM, pre-embedding immunocytochemistry allows
      the discrimination of cellular elements with few distinctive features and
      identification criteria (e.g., microglial perikarya and processes, when using an
      antibody against the microglia-specific marker Iba1 (ionized calcium binding
      adaptor molecule 1; as presented here)), identifying the neurotransmitter
      contents of cellular elements (e.g., serotonergic) and their ultrastructural
      localization of soluble or membrane-bound proteins (e.g., 5 HT1A and EphA4
      receptors). Here, we describe a protocol for transcardiac perfusion of mice with
      acrolein fixative, removal and sectioning of the brain, as well as
      immunoperoxidase-diaminobenzidine (DAB) staining, resin embedding, and ultrathin
      sectioning of the brain sections. Upon completion of these procedures, the
      immunostained material is ready for examination with TEM. When rigorously
      performed, this technique provides an excellent compromise between optimal
      ultrastructural preservation and immunocytochemical detection.

PMID- 20689506
TI  - The vermicelli and capellini handling tests: simple quantitative measures of
      dexterous forepaw function in rats and mice.
AB  - Previous characterizations of rodent eating behavior have revealed that they use
      coordinated forepaw movements to manipulate food pieces. We have extended upon
      this work to develop a simple quantitative measure of forepaw dexterity that is
      sensitive to lateralized impairments and age-dependent changes. Rodents learn
      skillful forepaw and digit movements to manage thin pasta pieces, which they
      eagerly consume. We have previously described methods for quantifying vermicelli
      handling in rats and showed that the measures are very sensitive to forelimb
      impairments resulting from unilateral ischemic lesions, middle cerebral artery
      occlusions and unilateral striatal dopamine depletion [Allred, R.P., Adkins,
      D.L., Woodlee, M.T., Husbands, L.C., Maldonado M.A., Kane, J.R., Schallert, T. &
      Jones, T.A. The Vermicelli Handling Test: a simple quantitative measure of
      dexterous forepaw function in rats. J. Neurosci. Methods 170, 229-244 (2008)].
      Here we present a more detailed protocol for this test in rats and compare it
      with a newly developed version for mice, the Capellini Handling Test. Rats and
      mice are videotaped while handling short lengths of uncooked vermicelli or
      capellini pasta, respectively, with a camera positioned to optimize the view of
      paw movements. Slow motion video playback allows for the identification of
      forepaw adjustments, defined as any distinct removal and replacement of the paw,
      or of any number of digits, on the pasta piece after eating commences. Forepaw
      adjustments per piece are averaged over trials per each testing session. Repeated
      testing permits sensitive quantitative analysis of changes in forepaw dexterity
      over time. Protocols for pre-testing habituation and handling practice, as well
      as procedures for characterizing atypical handling patterns, are described.
      Because rats and mice perform the pasta handling tests slightly differently,
      species-specific differences in administration and scoring of these tests are
      highlighted. All animal use was in accordance with protocols approved by the
      University of Texas at Austin Animal Care and Use Committee.

PMID- 20689507
TI  - Assessment of ultrasonic vocalizations during drug self-administration in rats.
AB  - Drug self-administration procedures are commonly used to study behavioral and
      neurochemical changes associated with human drug abuse, addiction and relapse.
      Various types of behavioral activity are commonly utilized as measures of drug
      motivation in animals. However, a crucial component of drug abuse relapse in
      abstinent cocaine users is "drug craving", which is difficult to model in
      animals, as it often occurs in the absence of overt behaviors. Yet, it is
      possible that a class of ultrasonic vocalizations (USVs) in rats may be a useful
      marker for affective responses to drug administration, drug anticipation and even
      drug craving. Rats vocalize in ultrasonic frequencies that serve as a
      communicatory function and express subjective emotional states. Several studies
      have shown that different call frequency ranges are associated with negative and
      positive emotional states. For instance, high frequency calls ("50-kHz") are
      associated with positive affect, whereas low frequency calls ("22-kHz") represent
      a negative emotional state. This article describes a procedure to assess rat USVs
      associated with daily cocaine self-administration. For this procedure, we
      utilized standard single-lever operant chambers housed within sound-attenuating
      boxes for cocaine self-administration sessions and utilized ultrasonic
      microphones, multi-channel recording hardware and specialized software programs
      to detect and analyze USVs. USVs measurements reflect emotionality of rats
      before, during and after drug availability and can be correlated with commonly
      assessed drug self-administration behavioral data such lever responses, inter
      response intervals and locomotor activity. Since USVs can be assessed during
      intervals prior to drug availability (e.g., anticipatory USVs) and during drug
      extinction trials, changes in affect associated with drug anticipation and drug
      abstinence can also be determined. In addition, determining USV changes over the
      course of short- and long-term drug exposure can provide a more detailed
      interpretation of drug exposure effects on affective functioning.

PMID- 20689508
TI  - In situ subcellular fractionation of adherent and non-adherent mammalian cells.
AB  - Protein function is intimately coupled to protein localization. Although some
      proteins are restricted to a specific location or subcellular compartment, many
      proteins are present as a freely diffusing population in free exchange with a sub
      population that is tightly associated with a particular subcellular domain or
      structure. In situ subcellular fractionation allows the visualization of protein
      compartmentalization and can also reveal protein sub-populations that localize to
      specific structures. For example, removal of soluble cytoplasmic proteins and
      loosely held nuclear proteins can reveal the stable association of some
      transcription factors with chromatin. Subsequent digestion of DNA can in some
      cases reveal association with the network of proteins and RNAs that is
      collectively termed the nuclear scaffold or nuclear matrix. Here we describe the
      steps required during the in situ fractionation of adherent and non-adherent
      mammalian cells on microscope coverslips. Protein visualization can be achieved
      using specific antibodies or fluorescent fusion proteins and fluorescence
      microscopy. Antibodies and/or fluorescent dyes that act as markers for specific
      compartments or structures allow protein localization to be mapped in detail. In
      situ fractionation can also be combined with western blotting to compare the
      amounts of protein present in each fraction. This simple biochemical approach can
      reveal associations that would otherwise remain undetected.

PMID- 20689509
TI  - Basics of multivariate analysis in neuroimaging data.
AB  - Multivariate analysis techniques for neuroimaging data have recently received
      increasing attention as they have many attractive features that cannot be easily
      realized by the more commonly used univariate, voxel-wise, techniques(1,4,5,6,7).
      Multivariate approaches evaluate correlation/covariance of activation across
      brain regions, rather than proceeding on a voxel-by-voxel basis. Thus, their
      results can be more easily interpreted as a signature of neural networks.
      Univariate approaches, on the other hand, cannot directly address interregional
      correlation in the brain. Multivariate approaches can also result in greater
      statistical power when compared with univariate techniques, which are forced to
      employ very stringent corrections for voxel-wise multiple comparisons. Further,
      multivariate techniques also lend themselves much better to prospective
      application of results from the analysis of one dataset to entirely new datasets.
      Multivariate techniques are thus well placed to provide information about mean
      differences and correlations with behavior, similarly to univariate approaches,
      with potentially greater statistical power and better reproducibility checks. In
      contrast to these advantages is the high barrier of entry to the use of
      multivariate approaches, preventing more widespread application in the community.
      To the neuroscientist becoming familiar with multivariate analysis techniques, an
      initial survey of the field might present a bewildering variety of approaches
      that, although algorithmically similar, are presented with different emphases,
      typically by people with mathematics backgrounds. We believe that multivariate
      analysis techniques have sufficient potential to warrant better dissemination.
      Researchers should be able to employ them in an informed and accessible manner.
      The current article is an attempt at a didactic introduction of multivariate
      techniques for the novice. A conceptual introduction is followed with a very
      simple application to a diagnostic data set from the Alzheimer s Disease
      Neuroimaging Initiative (ADNI), clearly demonstrating the superior performance of
      the multivariate approach.

PMID- 20689510
TI  - Labeling and imaging cells in the zebrafish hindbrain.
AB  - Key to understanding the morphogenetic processes that shape the early vertebrate
      embryo is the ability to image cells at high resolution. In zebrafish embryos,
      injection of plasmid DNA results in mosaic expression, allowing for the
      visualization of single cells or small clusters of cells (1) . We describe how
      injection of plasmid DNA encoding membrane-targeted Green Fluorescent Protein
      (mGFP) under the control of a ubiquitous promoter can be used for imaging cells
      undergoing neurulation. Central to this protocol is the methodology for imaging
      labeled cells at high resolution in sections and also in real time. This protocol
      entails the injection of mGFP DNA into young zebrafish embryos. Embryos are then
      processed for vibratome sectioning, antibody labeling and imaging with a confocal
      microscope. Alternatively, live embryos expressing mGFP can be imaged using time
      lapse confocal microscopy. We have previously used this straightforward approach
      to analyze the cellular behaviors that drive neural tube formation in the
      hindbrain region of zebrafish embryos (2). The fixed preparations allowed for
      unprecedented visualization of cell shapes and organization in the neural tube
      while live imaging complemented this approach enabling a better understanding of
      the cellular dynamics that take place during neurulation.

PMID- 20689511
TI  - Primer-free aptamer selection using a random DNA library.
AB  - Aptamers are highly structured oligonucleotides (DNA or RNA) that can bind to
      targets with affinities comparable to antibodies (1). They are identified through
      an in vitro selection process called Systematic Evolution of Ligands by
      EXponential enrichment (SELEX) to recognize a wide variety of targets, from small
      molecules to proteins and other macromolecules (2-4). Aptamers have properties
      that are well suited for in vivo diagnostic and/or therapeutic applications:
      Besides good specificity and affinity, they are easily synthesized, survive more
      rigorous processing conditions, they are poorly immunogenic, and their relatively
      small size can result in facile penetration of tissues. Aptamers that are
      identified through the standard SELEX process usually comprise approximately 80
      nucleotides (nt), since they are typically selected from nucleic acid libraries
      with approximately 40 nt long randomized regions plus fixed primer sites of
      approximately 20 nt on each side. The fixed primer sequences thus can comprise
      nearly approximately 50% of the library sequences, and therefore may positively
      or negatively compromise identification of aptamers in the selection process (3),
      although bioinformatics approaches suggest that the fixed sequences do not
      contribute significantly to aptamer structure after selection (5). To address
      these potential problems, primer sequences have been blocked by complementary
      oligonucleotides or switched to different sequences midway during the rounds of
      SELEX (6), or they have been trimmed to 6-9 nt (7, 8). Wen and Gray (9) designed
      a primer-free genomic SELEX method, in which the primer sequences were completely
      removed from the library before selection and were then regenerated to allow
      amplification of the selected genomic fragments. However, to employ the
      technique, a unique genomic library has to be constructed, which possesses
      limited diversity, and regeneration after rounds of selection relies on a linear
      reamplification step. Alternatively, efforts to circumvent problems caused by
      fixed primer sequences using high efficiency partitioning are met with problems
      regarding PCR amplification (10). We have developed a primer-free (PF) selection
      method that significantly simplifies SELEX procedures and effectively eliminates
      primer-interference problems (11, 12). The protocols work in a straightforward
      manner. The central random region of the library is purified without extraneous
      flanking sequences and is bound to a suitable target (for example to a purified
      protein or complex mixtures such as cell lines). Then the bound sequences are
      obtained, reunited with flanking sequences, and re-amplified to generate selected
      sub-libraries. As an example, here we selected aptamers to S100B, a protein
      marker for melanoma. Binding assays showed Kd s in the 10(-7) - 10(-8) M range
      after a few rounds of selection, and we demonstrate that the aptamers function
      effectively in a sandwich binding format.

PMID- 20689512
TI  - In vivo imaging of transgenic Leishmania parasites in a live host.
AB  - Distinct species of Leishmania, a protozoan parasite of the family
      Trypanosomatidae, typically cause different human disease manifestations. The
      most common forms of disease are visceral leishmaniasis (VL) and cutaneous
      leishmaniasis (CL). Mouse models of leishmaniasis are widely used, but
      quantification of parasite burdens during murine disease requires mice to be
      euthanized at various times after infection. Parasite loads are then measured
      either by microscopy, limiting dilution assay, or qPCR amplification of parasite
      DNA. The in vivo imaging system (IVIS) has an integrated software package that
      allows the detection of a bioluminescent signal associated with cells in living
      organisms. Both to minimize animal usage and to follow infection longitudinally
      in individuals, in vivo models for imaging Leishmania spp. causing VL or CL were
      established. Parasites were engineered to express luciferase, and these were
      introduced into mice either intradermally or intravenously. Quantitative
      measurements of the luciferase driving bioluminescence of the transgenic
      Leishmania parasites within the mouse were made using IVIS. Individual mice can
      be imaged multiple times during longitudinal studies, allowing us to assess the
      inter-animal variation in the initial experimental parasite inocula, and to
      assess the multiplication of parasites in mouse tissues. Parasites are detected
      with high sensitivity in cutaneous locations. Although it is very likely that the
      signal (photons/second/parasite) is lower in deeper visceral organs than the
      skin, but quantitative comparisons of signals in superficial versus deep sites
      have not been done. It is possible that parasite numbers between body sites
      cannot be directly compared, although parasite loads in the same tissues can be
      compared between mice. Examples of one visceralizing species (L. infantum
      chagasi) and one species causing cutaneous leishmaniasis (L. mexicana) are shown.
      The IVIS procedure can be used for monitoring and analyzing small animal models
      of a wide variety of Leishmania species causing the different forms of human
      leishmaniasis.

PMID- 20689513
TI  - Deficient Pms2, ERCC1, Ku86, CcOI in field defects during progression to colon
      cancer.
AB  - In carcinogenesis, the "field defect" is recognized clinically because of the
      high propensity of survivors of certain cancers to develop other malignancies of
      the same tissue type, often in a nearby location. Such field defects have been
      indicated in colon cancer. The molecular abnormalities that are responsible for a
      field defect in the colon should be detectable at high frequency in the
      histologically normal tissue surrounding a colonic adenocarcinoma or surrounding
      an adenoma with advanced neoplasia (well on the way to a colon cancer), but at
      low frequency in the colonic mucosa from patients without colonic neoplasia.
      Using immunohistochemistry, entire crypts within 10 cm on each side of colonic
      adenocarcinomas or advanced colonic neoplasias were found to be frequently
      reduced or absent in expression for two DNA repair proteins, Pms2 and/or ERCC1.
      Pms2 is a dual role protein, active in DNA mismatch repair as well as needed in
      apoptosis of cells with excess DNA damage. ERCC1 is active in DNA nucleotide
      excision repair. The reduced or absent expression of both ERCC1 and Pms2 would
      create cells with both increased ability to survive (apoptosis resistance) and
      increased level of mutability. The reduced or absent expression of both ERCC1 and
      Pms2 is likely an early step in progression to colon cancer. DNA repair gene Ku86
      (active in DNA non-homologous end joining) and Cytochrome c Oxidase Subunit I
      (involved in apoptosis) had each been reported to be decreased in expression in
      mucosal areas close to colon cancers. However, immunohistochemical evaluation of
      their levels of expression showed only low to modest frequencies of crypts to be
      deficient in their expression in a field defect surrounding colon cancer or
      surrounding advanced colonic neoplasia. We show, here, our method of evaluation
      of crypts for expression of ERCC1, Pms2, Ku86 and CcOI. We show that frequency of
      entire crypts deficient for Pms2 and ERCC1 is often as great as 70% to 95% in 20
      cm long areas surrounding a colonic neoplasia, while frequency of crypts
      deficient in Ku86 has a median value of 2% and frequency of crypts deficient in
      CcOI has a median value of 16% in these areas. The entire colon is 150 cm long
      (about 5 feet) and has about 10 million crypts in its mucosal layer. The defect
      in Pms2 and ERCC1 surrounding a colon cancer thus may include 1 million crypts.
      It is from a defective crypt that colon cancer arises.

PMID- 20689514
TI  - Does compassion for a family justify providing futile CPR?

PMID- 20689515
TI  - Resistin levels in preterms: are they influenced by fetal inflammatory course?
AB  - OBJECTIVE: Many different factors are involved in the pathogenesis of preterm
      deliveries and among them maternal or perinatal infections and inflammatory
      response have the major role. Researches were carried out about resistin, which
      is thought to have a role in inflammatory cytokine cycle and it was shown to be
      associated with growth in neonates. However, no research has been carried out
      showing its relationship with inflammation in neonates. In this study, we aimed
      to evaluate the resistin levels in premature neonates and the effect of events
      such as preterm prelabour rupture of the membranes (PPROMs) and the use of
      antenatal steroids on these levels. STUDY DESIGN: The study included 118 preterm
      neonates. Their medical data together with their mothers' were recorded. Serum
      resistin levels together with interleukin (IL)-6, C-reactive protein (CRP) and
      procalcitonin were evaluated in the first 2 h of life. RESULT: Mean gestational
      age and birth weight of babies included in the study were 29.6 +/- 2.7 weeks and
      1306.4 +/- 393.4 g, respectively. Babies with PPROMs had significantly higher
      levels of resistin ((n=30); 70.7 (7.8 to 568.4) ng ml(-1)) than babies without
      PPROM ((n=88); 25.9 (5.5 to 528.9) ng ml(-1)) (P=0.005), and the babies of
      mothers who received antenatal steroids had significantly lower resistin levels
      ((n=44); 20.8 (5.5 to 159.9) ng ml(-1)) than the babies of mothers who did not
      ((n=66); 34.6 (7.2 to 568.4) ng ml(-1)) (P=0.015). There were significant
      correlations between resistin and IL-6 levels and between IL-6 and procalcitonin
      and CRP levels in babies whose mothers did not receive antenatal steroids.
      However, no correlation was found between these parameters in babies whose
      mothers received antenatal steroids. CONCLUSION: Preterm delivery and PPROM
      involve complex cascade of events including inflammation, and steroids are potent
      anti-inflammatory agents. Elevated resistin levels in babies with PPROM and
      suppressed levels in babies whose mothers received antenatal steroids reported in
      this study might have been observed as a result of the effects of fetal
      inflammation on resistin levels.

PMID- 20689516
TI  - Association of cord blood platelet count and volume with hemoglobin in healthy
      term infants.
AB  - OBJECTIVE: The aim of this study was to investigate relationships of cord blood
      cells in healthy term infants both from vaginal and Cesarean sections. STUDY
      DESIGN: The study sample comprised 167 consecutive cord blood collections
      accepted for processing in an accredited cord blood bank. The effect of varying
      anticoagulant-to-blood ratio was excluded by standardizing the cell
      concentrations to reflect the values in native blood. Statistical analysis
      included descriptive statistics, simple linear regression analysis, Mann-Whitney
      U-test, cumulative frequency plots and Smirnov two-sample test. RESULT: As
      expected, hemoglobin correlated with red blood cell concentration. Interestingly,
      mean platelet volume was associated with hemoglobin, red blood cell concentration
      and hematocrit. The platelet count was inversely associated with the parameters.
      CONCLUSION: The observed associations of cord blood hemoglobin with mean platelet
      volume and platelet count reflect the physiology of fetal hematopoiesis at term.

PMID- 20689517
TI  - Antenatal education for expectant mothers results in sustained improvement in
      knowledge of newborn care.
AB  - OBJECTIVE: Basic perinatal education to increase parental knowledge of neonatal
      illnesses (such as respiratory distress, sepsis, complications of prematurity)
      could be a feasible way to reduce high neonatal mortality rates in limited
      resource nurseries. To assess the efficacy of antenatal education in increasing
      mothers' knowledge of basic newborn care in a limited-resource nursery, and to
      determine whether the knowledge is retained postpartum. STUDY DESIGN: In March to
      April 2008, we implemented a 10-min educational program on basic neonatal care
      for women receiving prenatal care in a maternal child hospital in Vientiane,
      Laos. The educational intervention was a structured, face-to-face interactive
      module taught by Lao providers using pictographic and written materials about
      temperature control, umbilical cord care and signs of neonatal illness. We
      assessed knowledge before and immediately after the module using a standardized
      interview tool. When possible, we reassessed knowledge postpartum to determine
      whether they retained information after the training. RESULT: We recruited 101
      women (average age=26.3 years), and the majority (53%) were primigravidas.
      Participants were well educated by local standards; 57% of women had >8 years and
      28% had >12 years of education. Women's knowledge of neonatal care increased by
      10% on immediate posttest (P<0.0001), especially regarding knowledge of umbilical
      cord care and temperature control (normal temperature ranges, thermometer use).
      Maternal education (P=0.025) and previous births (P=0.037) correlated positively
      with higher pretest scores. Higher maternal education correlated with higher
      posttest scores (P=0.01); however, less-educated women increased their scores as
      much as did women with more education. Nulliparous women also increased their
      posttest scores to comparable levels in women with previous deliveries. Women
      retested after delivery retained the educational message, achieving similar
      posttest and postdelivery scores (P=0.08). CONCLUSION: Brief antenatal education
      increases mothers' understanding of basic newborn care. Mothers retain this
      knowledge into the early postpartum period and during early infancy when it might
      help reduce morbidity and mortality. The education was efficacious for women with
      little education. Brief antenatal educational modules seem a feasible,
      sustainable means of improving mothers' knowledge of newborn care. We speculate
      that similar programs could improve neonatal morbidity and mortality in
      developing countries.

PMID- 20689518
TI  - Comparison between one and three doses a week of recombinant erythropoietin in
      very low birth weight infants.
AB  - OBJECTIVE: To compare transfusion requirements and erythropoietic response in
      preterms between schedules of rEPO administration once or three times per week,
      using the same weekly dose. STUDY DESIGN: Prospective, randomized trial including
      infants weighing <1500 g at birth and/or were ?32 weeks' gestation: Group 1 (60
      infants) received subcutaneous rEPO at 250 units kg(-1) per dose, three times
      weekly for 6 weeks; Group 2 (59 infants), at 750 units kg(-1) per dose, once
      weekly for 6 weeks. Efficacy was evaluated based on the transfusion requirement,
      hemoglobin changes, reticulocyte counts, serum transferrin receptor (sTfR) and
      serum ferritin. The frequency of adverse effects was registered in both groups.
      RESULT: A total of 13 infants were transfused in each group (relative risk: 0.98;
      95% confidence interval: 0.4 to 2.3). Phlebotomy loss and red blood cell
      transfusion volumes received were similar in both groups. Hemoglobin levels were
      lower at end of study in Group 2 (10.6+/-1.5 g dl(-1) versus 11.5+/-1.4 g dl(-1);
      P<0.003). At end of study, reticulocyte counts and sTfR values increased and
      serum ferritin values decreased, without significant differences between the two
      groups. Incidence of complications was similar in both groups. CONCLUSION: The
      once-weekly rEPO schedule for very low birth weight infants proved as effective
      as the three-times-weekly schedule, in relation to erythropoietic stimulus and
      transfusion requirement.

PMID- 20689520
TI  - Making the most of peer review.
AB  - The 'climategate' controversy exposed aspects of the peer review process that are
      normally kept secret, and has prompted a discussion on ways to improve peer
      review.

PMID- 20689519
TI  - The counter-regulatory effects of ESE-1 during angiotensin II-mediated vascular
      inflammation and remodeling.
AB  - BACKGROUND: Angiotensin II (Ang II) is a critical mediator vascular inflammation
      and remodeling in a number of diseases including hypertension and
      atherosclerosis. The purpose of this study was to evaluate the role of the
      epithelium-specific ETS transcription factor-1 (ESE-1), a member of E26
      transformation-specific sequence (ETS) transcription factors, as a mediator of
      Ang II-mediated vascular responses. METHODS: ESE-1 knockout mice were used to
      evaluate the role of ESE-1 in regulating Ang II-mediated vascular inflammation
      and remodeling. RESULTS: ESE-1 levels are low to undetectable under basal
      conditions but rapidly increase in response to Ang II. Intimal medial thickness
      and perivascular fibrosis of the aorta were significantly greater in ESE-1
      knockout mice compared with the wild-type littermate controls. Proliferating cell
      nuclear antigen (PCNA) staining was also greater in the aorta of the Ang II
      infused ESE-1 knockout mice compared with the controls. The infiltration of T
      cells and macrophage into the vessel wall of the aorta was dramatically enhanced
      in the ESE-1 knockout mice compared with the controls. Finally, Ang II-induced
      expression of a known downstream target of ESE-1, nitric oxide synthase 2 (NOS2),
      was significantly blunted in ESE-1 knockout mice compared to littermate controls.
      The alterations in vascular inflammation and remodeling were associated with an
      exaggerated systolic blood pressure response to Ang II in ESE-1 knockout mice.
      CONCLUSIONS: ESE-1 is an Ang II-inducible transcription factor that plays an
      important counter-regulatory role in the setting of vascular inflammation and
      remodeling.

PMID- 20689522
TI  - Nanomaterials: Graphene rolls off the press.

PMID- 20689523
TI  - Nanobiotechnology: Remote control of cells.

PMID- 20689526
TI  - A cure for cancer research.

PMID- 20689524
TI  - Plasmonics: New twist on nanoscale motors.

PMID- 20689527
TI  - After Avandia, some seek split in drug approval and monitoring.

PMID- 20689528
TI  - Fewer shots proposed to increase uptake of HPV vaccine.

PMID- 20689529
TI  - Chronic controversy continues over mysterious XMRV virus.

PMID- 20689530
TI  - Fight for subject confidentiality threatens disaster research.

PMID- 20689531
TI  - Lab-grown organs seen as remedy for long donor waitlists.

PMID- 20689532
TI  - Gap in stem cell funding could drive Australian brain drain.

PMID- 20689533
TI  - Stem cells serve as new platform for biodefense preparedness.

PMID- 20689534
TI  - Teaching hospitals urged to disclose clinical conflicts of interest.

PMID- 20689535
TI  - Educators dissect the future of medical training.

PMID- 20689536
TI  - Advocates to bring rare disease philanthropy under one umbrella.

PMID- 20689537
TI  - Big pharma moves from 'blockbusters' to 'niche busters'.

PMID- 20689539
TI  - Straight talk with ... Peter Piot.

PMID- 20689540
TI  - Parse the salt, please.

PMID- 20689541
TI  - Tech meets bio.

PMID- 20689542
TI  - Prepare for the long haul of drug monitoring.

PMID- 20689544
TI  - Neutrophils release brakes of coagulation.

PMID- 20689545
TI  - Turning on the angiogenic microswitch.

PMID- 20689546
TI  - A needle in the 'cancer vaccine' haystack.

PMID- 20689547
TI  - Glutamate joins the ranks of immunomodulators.

PMID- 20689548
TI  - Targeting dendritic cell metabolism in cancer.

PMID- 20689549
TI  - Mutant mice challenged as models of injury in the central nervous system.

PMID- 20689550
TI  - A double agent in cancer: deciphering macrophage roles in human tumors.

PMID- 20689551
TI  - A double agent in cancer: stopping macrophages wounds tumors.

PMID- 20689553
TI  - COP9 signalosome subunit 8 is required for postnatal hepatocyte survival and
      effective proliferation.
AB  - Studies using lower organisms and cultured mammalian cells have revealed that the
      COP9 signalosome (CSN) has important roles in multiple cellular processes.
      Conditional gene targeting was recently used to study CSN function in murine T
      cell development and activation. Using the Cre-loxP system, here we have achieved
      postnatal hepatocyte-restricted knockout of the csn8 gene (HR-Csn8KO) in mice.
      The protein abundance of other seven CSN subunits was differentially
      downregulated by HR-Csn8KO and the deneddylation of all cullins examined was
      significantly impaired. Moreover, HR-Csn8KO-induced massive hepatocyte apoptosis
      and evoked extensive reparative responses in the liver, including marked
      intralobular proliferation of biliary lineage cells and trans-differentiation and
      proliferation of the oval cells. However, division of pre-existing hepatocytes
      was significantly diminished in HR-Csn8KO livers. These findings indicate that
      Csn8 is essential to the ability of mature hepatocytes to proliferate effectively
      in response to hepatic injury. The histopathological examinations revealed
      striking hepatocytomegaly in Csn8-deficient livers. The hepatocyte nuclei were
      dramatically enlarged and pleomorphic with hyperchromasia and prominent nucleoli,
      consistent with dysplasia or preneoplastic cellular alteration in HR-Csn8KO mice
      at 6 weeks. Pericellular and perisinusoid fibrosis with distorted architecture
      was also evident at 6 weeks. It is concluded that CSN8/CSN is essential to
      postnatal hepatocyte survival and effective proliferation.

PMID- 20689554
TI  - BMP signalling permits population expansion by preventing premature myogenic
      differentiation in muscle satellite cells.
AB  - Satellite cells are the resident stem cells of adult skeletal muscle, supplying
      myonuclei for homoeostasis, hypertrophy and repair. In this study, we have
      examined the role of bone morphogenetic protein (BMP) signalling in regulating
      satellite cell function. Activated satellite cells expressed BMP receptor type 1A
      (BMPR-1A/Alk-3) and contained phosphorylated Smad proteins, indicating that BMP
      signalling is operating during proliferation. Indeed, exogenous BMP4 stimulated
      satellite cell division and inhibited myogenic differentiation. Conversely,
      interfering with the interactions between BMPs and their receptors by the
      addition of either the BMP antagonist Noggin or soluble BMPR-1A fragments,
      induced precocious differentiation. Similarly, blockade of BMP signalling by
      siRNA-mediated knockdown of BMPR-1A, disruption of the intracellular pathway by
      either Smad5 or Smad4 knockdown or inhibition of Smad1/5/8 phosphorylation with
      Dorsomorphin, also caused premature myogenic differentiation. BMP signalling
      acted to inhibit the upregulation of genes associated with differentiation, in
      part, through regulating Id1. As satellite cells differentiated, Noggin levels
      increased to antagonise BMP signalling, since Noggin knockdown enhanced
      proliferation and impeded myoblast fusion into large multinucleated myotubes.
      Finally, interference of normal BMP signalling after muscle damage in vivo
      perturbed the regenerative process, and resulted in smaller regenerated
      myofibres. In conclusion, BMP signalling operates during routine satellite cell
      function to help coordinate the balance between proliferation and
      differentiation, before Noggin is activated to antagonise BMPs and facilitate
      terminal differentiation.

PMID- 20689555
TI  - p53 directly transactivates Delta133p53alpha, regulating cell fate outcome in
      response to DNA damage.
AB  - We have previously reported that the human p53 gene encodes at least nine
      different p53 isoforms, including Delta133p53alpha, which can modulate p53
      transcriptional activity and apoptosis. In this study, we aimed to investigate
      the regulation of Delta133p53alpha isoform expression and its physiological role
      in modulating cell cycle arrest and apoptosis. We report here that in response to
      a low dose of doxorubicin (which induces cell cycle arrest without promoting
      apoptosis), p53 directly transactivates the human p53 internal promoter, inducing
      Delta133p53alpha protein expression. The induced Delta133p53alpha then inhibits
      p53-dependent apoptosis and G1 arrest without inhibiting p53-dependent G2 arrest.
      Therefore, endogenous Delta133p53alpha does not exclusively function in a
      dominant-negative manner toward p53, but differentially regulates cell cycle
      arrest and apoptosis.

PMID- 20689556
TI  - Mutant p53(R175H) upregulates Twist1 expression and promotes epithelial
      mesenchymal transition in immortalized prostate cells.
AB  - A mutation within one allele of the p53 tumor suppressor gene can inactivate the
      remaining wild-type allele in a dominant-negative manner and in some cases can
      exert an additional oncogenic activity, known as mutant p53 'gain of function'
      (GOF). To study the role of p53 mutations in prostate cancer and to discriminate
      between the dominant-negative effect and the GOF activity of mutant p53, we
      measured, using microarrays, the expression profiles of three immortalized
      prostate epithelial cultures expressing wild-type, inactivated p53 or mutated
      p53. Analysis of these gene expression profiles showed that both inactivated p53
      and p53(R175H) mutant expression resulted in the upregulation of cell cycle
      progression genes. A second group, which was upregulated exclusively by mutant
      p53(R175H), was predominantly enriched in developmental genes. This group of
      genes included the Twist1, a regulator of metastasis and epithelial-mesenchymal
      transition (EMT). Twist1 levels were also elevated in metastatic prostate cancer
      derived cell line DU145, in immortalized lung fibroblasts and in a subset of lung
      cancer samples, all in a mutant p53-dependent manner. p53(R175H) mutant bearing
      immortalized epithelial cells showed typical features of EMT, such as higher
      expression of mesenchymal markers, lower expression of epithelial markers and
      enhanced invasive properties in vitro. The mechanism by which p53(R175H) mutant
      induces Twist1 expression involves alleviation of the epigenetic repression. Our
      data suggest that Twist1 expression might be upregulated following p53 mutation
      in cancer cells.

PMID- 20689557
TI  - Enhanced contact allergen- and UVB-induced keratinocyte apoptosis in the absence
      of CD95/Fas/Apo-1.
AB  - FAS/CD95/Apo-1 is a ubiquitously expressed cell-surface receptor involved in the
      initiation of programmed cell death. Its function in epidermal keratinocytes has
      been incompletely defined. Available evidence from in vitro studies points to
      important roles of Fas in the pathogenesis of contact dermatitis and in
      keratinocyte apoptosis induced by ultraviolet light. To define functions of Fas
      in the epidermis in vivo, we have generated mice with epidermis-specific deletion
      of the fas gene and tested its requirement for 2,4-dinitrofluorobenzene-induced
      contact dermatitis and for ultraviolet light B (UVB)-induced keratinocyte
      apoptosis. We report here our unexpected finding that keratinocyte apoptosis
      induced by both a contact allergen and UVB irradiation was significantly enhanced
      in Fas-negative epidermis. Expression of Fas by epidermal keratinocytes was
      neither necessary for the normal development of contact hypersensitivity of the
      skin, nor required for keratinocyte apoptosis following UVB irradiation. Our
      study results thus show that in the epidermis in vivo Fas exerts antiapoptotic
      effects that outweigh its proapoptotic role in contact hypersensitivity responses
      of the skin and in the tissue response of the epidermis to UVB irradiation.

PMID- 20689558
TI  - Bid-mediated mitochondrial damage is a key mechanism in glutamate-induced
      oxidative stress and AIF-dependent cell death in immortalized HT-22 hippocampal
      neurons.
AB  - Glutamate toxicity involves increases in intracellular calcium levels and
      enhanced formation of reactive oxygen species (ROS) causing neuronal dysfunction
      and death in acute and chronic neurodegenerative disorders. The molecular
      mechanisms mediating glutamate-induced ROS formation are, however, still poorly
      defined. Using a model system that lacks glutamate-operated calcium channels, we
      demonstrate that glutamate-induced acceleration of ROS levels occurs in two steps
      and is initiated by lipoxygenases (LOXs) and then significantly accelerated
      through Bid-dependent mitochondrial damage. The Bid-mediated secondary boost of
      ROS formation downstream of LOX activity further involves mitochondrial
      fragmentation and release of mitochondrial apoptosis-inducing factor (AIF) to the
      nucleus. These data imply that the activation of Bid is an essential step in
      amplifying glutamate-induced formation of lipid peroxides to irreversible
      mitochondrial damage associated with further enhanced free radical formation and
      AIF-dependent execution of cell death.

PMID- 20689560
TI  - Parkinson disease: treatment of the nonmotor symptoms of Parkinson disease.
AB  - Dramatic advances have been made in the treatment of motor dysfunction in both
      the early and late phases of Parkinson disease. Effective therapies for the
      nonmotor symptoms of this disease, however, remain a major unmet clinical need. A
      recent study has highlighted the dearth of clinical trials for some of these
      symptoms.

PMID- 20689559
TI  - Mapping the life histories of T cells.
AB  - The behaviour of T cells is not fixed in the germ line, but is highly adaptable
      depending on experiences encountered during a T cell's life. To understand how
      different T cell subsets arise and how prior signalling input regulates
      subsequent T cell behaviour, approaches are required that couple a given T cell
      state to signals received by the cell, or by one of its ancestors, at earlier
      times. Here we describe recently developed technologies that have been used to
      determine the kinship of different T cell subsets and their prior functional
      characteristics. Furthermore, we discuss the potential value of new technologies
      that would allow assessment of T cell migration patterns and prior signalling
      events.

PMID- 20689561
TI  - Alzheimer disease: clinical use of cholinergic drugs in Alzheimer disease.
AB  - Drugs acting on the cholinergic system can improve or worsen cognitive abilities,
      and their effects are particularly pronounced in frail elderly individuals and
      patients with alzheimer disease. Guidelines are urgently needed on the judicious
      use of cholinergic drugs.

PMID- 20689562
TI  - Epilepsy: old drugs do the trick in childhood absence epilepsy.
AB  - A randomized, double-blind clinical trial that compared three widely used
      anticonvulsants for childhood absence epilepsy established that ethosuximide was
      the most appropriate first-line therapy for this condition. The study provides
      guidance for the treatment of this common childhood epilepsy where evidence-based
      recommendations have previously been lacking.

PMID- 20689563
TI  - Multiple sclerosis: monitoring long-term treatments in multiple sclerosis.
AB  - Patients with relapsing-remitting multiple sclerosis have been shown to benefit
      from disease-modifying treatments over prolonged periods. More focus should now
      be placed on monitoring the long-term evolution of this disease (making use of
      tools such as MRI), alongside the patients' response and adherence to such
      treatments.

PMID- 20689564
TI  - Parkinson disease: sialorrhea and Parkinson disease--novel treatment approaches.
AB  - Sialorrhea is a common and often debilitating, socially isolating and
      embarrassing symptom for patients with Parkinson disease (PD). The treatment of
      sialorrhea involves the management of saliva production, and is complicated in
      this disease by the risk of aspiration. Two novel approaches to the treatment of
      this symptom in PD have recently been published.

PMID- 20689565
TI  - Peripheral neuropathies: whole genome sequencing identifies causal variants in
      CMT.
AB  - For the first time, medical sequencing has been successfully performed at the
      genome level to identify the causative gene in an individual with autosomal
      recessive Charcot-Marie-Tooth disease. The results of sequencing a proband with
      this condition highlight some of the opportunities and challenges of this
      seemingly ultimate approach to human genetics research and diagnostics.

PMID- 20689566
TI  - Headache: migraine, magnetic stimulation and cortical excitability.
AB  - A new study indicates that single-pulse transcranial magnetic stimulation can
      provide substantial long-lasting pain relief in patients with migraine with aura.
      The findings suggest that non-pharmacological therapies could be used to
      successfully abort migraine attacks in patients who find that drug therapies do
      not adequately control migraine symptoms.

PMID- 20689567
TI  - Brain hemorrhage: assessing outcome after subarachnoid hemorrhage.
AB  - A meta-analysis of results from the oxford vascular study indicates that rates of
      mortality associated with subarachnoid hemorrhage have decreased over the past 30
      years. The study does not, however, address whether day-to-day functioning and
      quality of life in subarachnoid hemorrhage survivors have improved over the same
      time period.

PMID- 20689568
TI  - Utility of optic pathway glioma screening in young children with
      neurofibromatosis type I: questions generated by a clinical audit.
AB  - AIM: Neurofibromatosis type I (NFI) is a phakomatosis that affects approximately
      1 per 3000 live births. About 15% children with NFI develop optic pathway glioma
      (OPG). The Neurofibromatosis UK society recommend annual ophthalmic screening to
      identify those children who may have OPG affecting vision and refer for
      investigation and treatment as necessary. METHODS: We undertook a retrospective
      audit with three aims: (1) to elicit if departmental screening practice of
      children with NFI for OPG meets current guidelines, (2) to document the age at
      which tests of visual function are useful in the diagnosis and screening of OPG,
      and (3) to document the contribution eye screening has made to the diagnosis of
      OPG. RESULTS: A total of 37 children were identified from the clinic register.
      Overall 43% children met the criterion for an appropriate number of screening
      episodes. All the children met the visual acuity and optic disc assessment
      criteria; 84% met the pupil-testing criterion. No child was mature enough to
      perform visual fields or colour vision testing. CONCLUSION: Further education is
      required to encourage patients to attend eye clinic for screening as the majority
      of patients failing to reach the standard were due to non-attendances. No OPGs
      were detected during 128 screening episodes over approximately 7 years of
      screening. The authors question the usefulness of including visual field and
      colour vision assessment in the protocol for this age group.

PMID- 20689569
TI  - Ocular sarcoidosis in Thailand.
AB  - PURPOSE: To determine the prevalence of pulmonary sarcoidosis in patients with
      uveitis from the University Referral Centre in Thailand and to report on their
      clinical characteristics. METHODS: We performed a retrospective review of results
      of radiological examinations of 209 consecutive new patients, diagnosed with
      uveitis. In patients with signs of pulmonary sarcoidosis, we reviewed clinical
      characteristics including age, gender, laterality and anatomical location of
      uveitis, and complications. RESULTS: From 209 chest X-ray (CXR) examinations, one
      patient exhibited radiological signs typical of stage 1 sarcoidosis. Chest CT of
      three patients with posterior multifocal chorioretinitis (PMC) revealed
      abnormalities suggesting the diagnosis of pulmonary sarcoidosis. All PMC patients
      were females older than 50 years; they had no pulmonary complaints and their CXRs
      were without abnormalities. CONCLUSION: Ocular sarcoidosis is prevalent in
      Thailand and our findings suggest that possibly more patients with sarcoidosis
      would be identified if diagnosis was thought of and ancillary tests were
      performed.

PMID- 20689570
TI  - Retrospective case series on the long-term visual and intraocular pressure
      outcomes of phacomorphic glaucoma.
AB  - PURPOSE: To analyse the long-term visual acuity (VA) and intraocular pressure
      (IOP) outcomes in phacomorphic glaucoma. PATIENTS AND METHODS: A retrospective
      analysis of 100 consecutive, acute phacomorphic glaucoma cases from January 2000
      to April 2009 was conducted at The Caritas Medical Centre in Hong Kong. All cases
      underwent cataract extraction after IOP control with medication and/or laser.
      RESULTS: During a 3.1+/-2.6-year follow-up, the mean visual improvement was 1.1+/
      0.9 LogMAR units with improvements in 81.7% of cases. A shorter duration from
      symptoms to cataract extraction resulted in greater visual improvement (r(2)=0.1,
      P=0.001). In all, 80.5% of the cases had IOP<=21 mm Hg without any glaucoma
      treatment; 19.5% required 1.6+/-0.7 glaucoma eye drops; and 3.7% required
      additional laser iridotomy or trabeculectomy for IOP control at 1.8+/-2.3 years.
      The vertical cup-disc ratio (VCDR) of the index eye was 0.6+/-0.3. Gonioscopy
      revealed an averaged Shaffer grading of 3.0+/-1.0 and 99+/-90 degrees of
      peripheral anterior synechiae (PAS). The Humphrey automated perimetry mean
      deviation was 5.2+/-2.7 and the pattern standard deviation was -15.9+/-10.
      CONCLUSION: Over 80% of phacomorphic patients had long-term visual improvements
      and normalization of IOP after cataract extraction. A shorter attack seemed to
      offer better VA. Post-operatively, most have open angles with some degree of PAS
      formation, and glaucomatous optic neuropathy is evident from enlarged VCDRs and
      visual field defects. At least 2 years of follow-up is useful to detect a 20%
      glaucoma progression possibly requiring additional glaucoma treatments.

PMID- 20689571
TI  - Combinatory cytotoxic effects produced by E1B-55kDa-deleted adenoviruses and
      chemotherapeutic agents are dependent on the agents in esophageal carcinoma.
AB  - We examined possible combinatory antitumor effects of replication-competent type
      5 adenoviruses (Ad) lacking E1B-55kDa molecules (Ad-delE1B55) and
      chemotherapeutic agents in nine human esophageal carcinoma cells. Ad-delE1B55
      produced cytotoxic effects on all the carcinoma cells and the cytotoxicity is not
      directly linked with the p53 status of the tumors or with the infectivity to
      respective tumors. A combinatory treatment with Ad-delE1B55 and an anticancer
      agent, 5-fluorouracil (5-FU), mitomycin C or etoposide, produced greater
      cytotoxic effects than that with either the Ad or the agent. Administration of 5
      FU could minimally inhibit the viral replication and a simultaneous treatment
      with the Ad and 5-FU achieved better cytotoxicity than sequential treatments. We
      also confirmed the antitumor effects by the combination of Ad-delE1B55 with 5-FU
      in vivo. Cisplatin, however, did not achieve the combinatory effects in most of
      the cells tested. These data indicate that the Ad-delE1B55 produce combinatory
      antitumor effects with a chemotherapeutic agent irrespective of the
      administration schedule, but the effects depend on an agent in esophageal
      carcinoma.

PMID- 20689572
TI  - A phase I clinical trial of thymidine kinase-based gene therapy in advanced
      hepatocellular carcinoma.
AB  - The aim of this phase I clinical trial was to assess the feasibility and safety
      of intratumoral administration of a first-generation adenoviral vector encoding
      herpes simplex virus thymidine kinase (HSV-TK) gene (Ad.TK) followed by systemic
      ganciclovir to patients with advanced hepatocellular carcinoma (HCC).
      Secondarily, we have analyzed its antitumor effect. Ten patients were enrolled in
      five dose-level cohorts that received from 1010 to 2 * 1012 viral particles (vp).
      Ad.TK was injected intratumorally and patients received up to three doses at 30
      day intervals. Positron emission tomography was used to monitor TK gene
      expression. Ad.TK injection was feasible in 100% of cases. Treatment was well
      tolerated and dose-limiting toxicity was not achieved. Cumulative toxicity was
      not observed. Hepatic toxicity was absent even in cirrhotic patients. Fever, flu
      like syndrome, pain at the injection site and pancytopenia were the most common
      side effects. No partial responses were observed and 60% of patients showed tumor
      stabilization of the injected lesion. Importantly, two patients who received the
      highest dose showed signs of intratumoral necrosis by imaging procedures. One of
      them achieved a sustained stabilization and survived for 26 months. In
      conclusion, Ad.TK can be safely administered by intratumoral injection to
      patients with HCC up to 2 * 1012 vp per patient.

PMID- 20689573
TI  - Bilateral Descemet's stripping with endothelial keratoplasy for posterior
      polymorphous corneal dystrophy in a young phakic patient.

PMID- 20689574
TI  - Asymmetric Wolbachia segregation during early Brugia malayi embryogenesis
      determines its distribution in adult host tissues.
AB  - Wolbachia are required for filarial nematode survival and fertility and
      contribute to the immune responses associated with human filarial diseases. Here
      we developed whole-mount immunofluorescence techniques to characterize Wolbachia
      somatic and germline transmission patterns and tissue distribution in Brugia
      malayi, a nematode responsible for lymphatic filariasis. In the initial embryonic
      divisions, Wolbachia segregate asymmetrically such that they occupy only a small
      subset of cells in the developing embryo, facilitating their concentration in the
      adult hypodermal chords and female germline. Wolbachia are not found in male
      reproductive tissues and the absence of Wolbachia from embryonic germline
      precursors in half of the embryos indicates Wolbachia loss from the male germline
      may occur in early embryogenesis. Wolbachia rely on fusion of hypodermal cells to
      populate adult chords. Finally, we detect Wolbachia in the secretory canal lumen
      suggesting living worms may release bacteria and/or their products into their
      host.

PMID- 20689575
TI  - Psychological stress-induced, IDO1-dependent tryptophan catabolism: implications
      on immunosuppression in mice and humans.
AB  - It is increasingly recognized that psychological stress influences inflammatory
      responses and mood. Here, we investigated whether psychological stress (combined
      acoustic and restraint stress) activates the tryptophan (Trp) catabolizing enzyme
      indoleamine 2,3-dioxygenase 1(IDO1) and thereby alters the immune homeostasis and
      behavior in mice. We measured IDO1 mRNA expression and plasma levels of Trp
      catabolites after a single 2-h stress session and in repeatedly stressed (4.5
      days stress, 2-h twice a day) naive BALB/c mice. A role of cytokines in acute
      stress-induced IDO1 activation was studied after IFNgamma and TNFalpha blockade
      and in IDO1(-/-) mice. RU486 and 1-Methyl-L-tryptophan (1-MT) were used to study
      role of glucocorticoids and IDO1 on Trp depletion in altering the immune and
      behavioral response in repeatedly stressed animals. Clinical relevance was
      addressed by analyzing IDO1 activity in patients expecting abdominal surgery.
      Acute stress increased the IDO1 mRNA expression in brain, lung, spleen and
      Peyer's patches (max. 14.1+/-4.9-fold in brain 6-h after stress) and resulted in
      a transient depletion of Trp (-25.2+/-6.6%) and serotonin (-27.3+/-4.6%) from the
      plasma measured 6-h after stress while kynurenine levels increased 6-h later
      (11.2+/-9.3%). IDO1 mRNA up-regulation was blocked by anti-TNFalpha and anti
      IFNgamma treatment. Continuous IDO1 blockade by 1-MT but not RU486 treatment
      normalized the anti-bacterial defense and attenuated increased IL-10 inducibility
      in splenocytes after repeated stress as it reduced the loss of body weight and
      behavioral alterations. Moreover, kynurenic acid which remained increased in 1-MT
      treated repeatedly stressed mice was identified to reduce the TNFalpha
      inducibility of splenocytes in vitro and in vivo. Thus, psychological stress
      stimulates cytokine-driven IDO1 activation and Trp depletion which seems to have
      a central role for developing stress-induced immunosuppression and behavioral
      alteration. Since patients showed Trp catabolism already prior to surgery, IDO is
      also a possible target enzyme for humans modulating immune homeostasis and mood.

PMID- 20689576
TI  - Model of tooth morphogenesis predicts carabelli cusp expression, size, and
      symmetry in humans.
AB  - BACKGROUND: The patterning cascade model of tooth morphogenesis accounts for
      shape development through the interaction of a small number of genes. In the
      model, gene expression both directs development and is controlled by the shape of
      developing teeth. Enamel knots (zones of nonproliferating epithelium) mark the
      future sites of cusps. In order to form, a new enamel knot must escape the
      inhibitory fields surrounding other enamel knots before crown components become
      spatially fixed as morphogenesis ceases. Because cusp location on a fully formed
      tooth reflects enamel knot placement and tooth size is limited by the cessation
      of morphogenesis, the model predicts that cusp expression varies with intercusp
      spacing relative to tooth size. Although previous studies in humans have
      supported the model's implications, here we directly test the model's predictions
      for the expression, size, and symmetry of Carabelli cusp, a variation present in
      many human populations. METHODOLOGY/PRINCIPAL FINDINGS: In a dental cast sample
      of upper first molars (M1s) (187 rights, 189 lefts, and 185 antimeric pairs), we
      measured tooth area and intercusp distances with a Hirox digital microscope. We
      assessed Carabelli expression quantitatively as an area in a subsample and
      qualitatively using two typological schemes in the full sample. As predicted, low
      relative intercusp distance is associated with Carabelli expression in both right
      and left samples using either qualitative or quantitative measures. Furthermore,
      asymmetry in Carabelli area is associated with asymmetry in relative intercusp
      spacing. CONCLUSIONS/SIGNIFICANCE: These findings support the model's predictions
      for Carabelli cusp expression both across and within individuals. By comparing
      right-left pairs of the same individual, our data show that small variations in
      developmental timing or spacing of enamel knots can influence cusp pattern
      independently of genotype. Our findings suggest that during evolution new cusps
      may first appear as a result of small changes in the spacing of enamel knots
      relative to crown size.

PMID- 20689577
TI  - Visuospatial sequence learning without seeing.
AB  - BACKGROUND: The ability to detect and integrate associations between unrelated
      items that are close in space and time is a key feature of human learning and
      memory. Learning sequential associations between non-adjacent visual stimuli
      (higher-order visuospatial dependencies) can occur either with or without
      awareness (explicit vs. implicit learning) of the products of learning. Existing
      behavioural and neurocognitive studies of explicit and implicit sequence
      learning, however, are based on conscious access to the sequence of target
      locations and, typically, on conditions where the locations for orienting, or
      motor, responses coincide with the locations of the target sequence.
      METHODOLOGY/PRINCIPAL FINDINGS: Dichoptic stimuli were presented on a novel
      sequence learning task using a mirror stereoscope to mask the eye-of-origin of
      visual input from conscious awareness. We demonstrate that conscious access to
      the sequence of target locations and responses that coincide with structure of
      the target sequence are dispensable features when learning higher-order
      visuospatial associations. Sequence knowledge was expressed in the ability of
      participants to identify the trained higher-order visuospatial sequence on a
      recognition test, even though the trained and untrained recognition sequences
      were identical when viewed at a conscious binocular level, and differed only at
      the level of the masked sequential associations. CONCLUSIONS/SIGNIFICANCE: These
      results demonstrate that unconscious processing can support perceptual learning
      of higher-order sequential associations through interocular integration of
      retinotopic-based codes stemming from monocular eye-of-origin information.
      Furthermore, unlike other forms of perceptual associative learning, visuospatial
      attention did not need to be directed to the locations of the target sequence.
      More generally, the results pose a challenge to neural models of learning to
      account for a previously unknown capacity of the human visual system to support
      the detection, learning and recognition of higher-order sequential associations
      under conditions where observers are unable to see the target sequence or perform
      responses that coincide with structure of the target sequence.

PMID- 20689578
TI  - beta-diversity and species accumulation in antarctic coastal benthos: influence
      of habitat, distance and productivity on ecological connectivity.
AB  - High Antarctic coastal marine environments are comparatively pristine with strong
      environmental gradients, which make them important places to investigate
      biodiversity relationships. Defining how different environmental features
      contribute to shifts in beta-diversity is especially important as these shifts
      reflect both spatio-temporal variations in species richness and the degree of
      ecological separation between local and regional species pools. We used
      complementary techniques (species accumulation models, multivariate variance
      partitioning and generalized linear models) to assess how the roles of
      productivity, bio-physical habitat heterogeneity and connectivity change with
      spatial scales from metres to 100's of km. Our results demonstrated that the
      relative importance of specific processes influencing species accumulation and
      beta-diversity changed with increasing spatial scale, and that patterns were
      never driven by only one factor. Bio-physical habitat heterogeneity had a strong
      influence on beta-diversity at scales <290 km, while the effects of productivity
      were low and significant only at scales >40 km. Our analysis supports the
      emphasis on the analysis of diversity relationships across multiple spatial
      scales and highlights the unequal connectivity of individual sites to the
      regional species pool. This has important implications for resilience to habitat
      loss and community homogenisation, especially for Antarctic benthic communities
      where rates of recovery from disturbance are slow, there is a high ratio of poor
      dispersing and brooding species, and high biogenic habitat heterogeneity and
      spatio-temporal variability in primary production make the system vulnerable to
      disturbance. Consequently, large areas need to be included within marine
      protected areas for effective management and conservation of these special
      ecosystems in the face of increasing anthropogenic disturbance.

PMID- 20689579
TI  - APP intracellular domain impairs adult neurogenesis in transgenic mice by
      inducing neuroinflammation.
AB  - BACKGROUND: A devastating aspect of Alzheimer's disease (AD) is the progressive
      deterioration of memory due to neuronal loss. Amyloid precursor protein (APP)
      occupies a central position in AD and APP-derived amyloid-beta (Abeta) peptides
      are thought to play a pivotal role in disease pathogenesis. Nonetheless, it is
      becoming clear that AD etiology is highly complex and that factors other than
      Abeta also contribute to AD pathogenesis. APP intracellular domain (AICD) is
      generated together with Abeta and we recently showed that AICD transgenic mice
      recapitulate pathological features of AD such as tau hyperphosphorylation, memory
      deficits and neurodegeneration without increasing the Abeta levels. Since
      impaired adult neurogenesis is shown to augment memory deficits in AD mouse
      models, here we examined the status of adult neurogenesis in AICD transgenic
      mice. METHODOLOGY/PRINCIPAL FINDING: We previously generated transgenic mice co
      expressing 59-residue long AICD fragment and its binding partner Fe65.
      Hippocampal progenitor cell proliferation was determined by BrdU incorporation at
      1.5, 3 and 12 months of age. Only male transgenic and their respective wilt type
      littermate control mice were used. We find age-dependent decrease in BrdU
      incorporation and doublecortin-positive cells in the dentate gyrus of AICD
      transgenic mice suggesting impaired adult neurogenesis. This deficit resulted
      from decreased proliferation and survival, whereas neuronal differentiation
      remained unaffected. Importantly, this impairment was independent of Abeta since
      APP-KO mice expressing AICD also exhibit reduced neurogenesis. The defects in
      adult neurogenesis are prevented by long-term treatment with the non-steroidal
      anti-inflammatory agents ibuprofen or naproxen suggesting that neuroinflammation
      is critically involved in impaired adult neurogenesis in AICD transgenic mice.
      CONCLUSION/SIGNIFICANCE: Since adult neurogenesis is crucial for spatial memory,
      which is particularly vulnerable in AD, these findings suggest that AICD can
      exacerbate memory defects in AD by impairing adult neurogenesis. Our findings
      further establish that AICD, in addition to Abeta, contributes to AD pathology
      and that neuroinflammation plays a much broader role in AD pathogenesis than
      previously thought.

PMID- 20689580
TI  - Prediction of deleterious non-synonymous SNPs based on protein interaction
      network and hybrid properties.
AB  - Non-synonymous SNPs (nsSNPs), also known as Single Amino acid Polymorphisms
      (SAPs) account for the majority of human inherited diseases. It is important to
      distinguish the deleterious SAPs from neutral ones. Most traditional
      computational methods to classify SAPs are based on sequential or structural
      features. However, these features cannot fully explain the association between a
      SAP and the observed pathophysiological phenotype. We believe the better
      rationale for deleterious SAP prediction should be: If a SAP lies in the protein
      with important functions and it can change the protein sequence and structure
      severely, it is more likely related to disease. So we established a method to
      predict deleterious SAPs based on both protein interaction network and
      traditional hybrid properties. Each SAP is represented by 472 features that
      include sequential features, structural features and network features. Maximum
      Relevance Minimum Redundancy (mRMR) method and Incremental Feature Selection
      (IFS) were applied to obtain the optimal feature set and the prediction model was
      Nearest Neighbor Algorithm (NNA). In jackknife cross-validation, 83.27% of SAPs
      were correctly predicted when the optimized 263 features were used. The optimized
      predictor with 263 features was also tested in an independent dataset and the
      accuracy was still 80.00%. In contrast, SIFT, a widely used predictor of
      deleterious SAPs based on sequential features, has a prediction accuracy of
      71.05% on the same dataset. In our study, network features were found to be most
      important for accurate prediction and can significantly improve the prediction
      performance. Our results suggest that the protein interaction context could
      provide important clues to help better illustrate SAP's functional association.
      This research will facilitate the post genome-wide association studies.

PMID- 20689581
TI  - Correcting the bias of empirical frequency parameter estimators in codon models.
AB  - Markov models of codon substitution are powerful inferential tools for studying
      biological processes such as natural selection and preferences in amino acid
      substitution. The equilibrium character distributions of these models are almost
      always estimated using nucleotide frequencies observed in a sequence alignment,
      primarily as a matter of historical convention. In this note, we demonstrate that
      a popular class of such estimators are biased, and that this bias has an adverse
      effect on goodness of fit and estimates of substitution rates. We propose a
      "corrected" empirical estimator that begins with observed nucleotide counts, but
      accounts for the nucleotide composition of stop codons. We show via simulation
      that the corrected estimates outperform the de facto standard estimates not just
      by providing better estimates of the frequencies themselves, but also by leading
      to improved estimation of other parameters in the evolutionary models. On a
      curated collection of sequence alignments, our estimators show a significant
      improvement in goodness of fit compared to the approach. Maximum likelihood
      estimation of the frequency parameters appears to be warranted in many cases,
      albeit at a greater computational cost. Our results demonstrate that there is
      little justification, either statistical or computational, for continued use of
      the -style estimators.

PMID- 20689582
TI  - The human cytomegalovirus UL76 gene regulates the level of expression of the UL77
      gene.
AB  - BACKGROUND: Human cytomegalovirus (HCMV) can be reactivated under
      immunosuppressive conditions causing several fatal pneumonitis, hepatitis,
      retinitis, and gastrointestinal diseases. HCMV also causes deafness and mental
      retardation in neonates when primary infection has occurred during pregnancy. In
      the genome of HCMV at least 194 known open reading frames (ORFs) have been
      predicted, and approximately one-quarter, or 41 ORFs, are required for viral
      replication in cell culture. In contrast, the majority of the predicted ORFs are
      nonessential for viral replication in cell culture. However, it is also possible
      that these ORFs are required for the efficient viral replication in the host. The
      UL77 gene of HCMV is essential for viral replication and has a role in viral DNA
      packaging. The function of the upstream UL76 gene in the HCMV-infected cells is
      not understood. UL76 and UL77 are cistons on the same viral mRNA and a
      conventional 5' mRNA for UL77 has not been detected. The vast majority of
      eukaryotic mRNAs are monocistronic, i.e., they encode only a single protein.
      METHODOLOGY/PRINCIPAL FINDINGS: To determine whether the UL76 ORF affects UL77
      gene expression, we mutated UL76 by ORF frame-shifts, stop codons or deletion of
      the viral gene. The effect on UL77 protein expression was determined by either
      transfection of expression plasmids or infection with recombinant viruses.
      Mutation of UL76 ORF significantly increased the level of UL77 protein
      expression. However, deletion of UL76 upstream of the UL77 ORF had only marginal
      effects on viral growth. CONCLUSIONS/SIGNIFICANCE: While UL76 is not essential
      for viral replication, the UL76 ORF is involved in regulation of the level of
      UL77 protein expression in a manner dependent on the translation re-initiation.
      UL76 may fine-tune the UL77 expression for the efficient viral replication in the
      HCMV- infected cells.

PMID- 20689584
TI  - Differences in efficacy and safety of pharmaceutical treatments between men and
      women: an umbrella review.
AB  - Being male or female is an important determinant of risks for certain diseases,
      patterns of illness and life expectancy. Although differences in risks for and
      prognoses of several diseases have been well documented, sex-based differences in
      responses to pharmaceutical treatments and accompanying risks of adverse events
      are less clear. The objective of this umbrella review was to determine whether
      clinically relevant differences in efficacy and safety of commonly prescribed
      medications exist between men and women. We retrieved all available systematic
      reviews of the Oregon Drug Effectiveness Review Project published before January
      2010. Two persons independently reviewed each report to identify relevant
      studies. We dually abstracted data from the original publications into
      standardized forms. We synthesized the available evidence for each drug class and
      rated its quality applying the GRADE (Grading of Recommendations Assessment,
      Development and Evaluation) approach. Findings, based on 59 studies and data of
      more than 250,000 patients suggested that for the majority of drugs no
      substantial differences in efficacy and safety exist between men and women. Some
      clinically important exceptions, however, were apparent: women experienced
      substantially lower response rates with newer antiemetics than men (45% vs. 58%;
      relative risk 1.49, 95% confidence interval 1.35-1.64); men had higher rates of
      sexual dysfunction than women while on paroxetine for major depressive disorder;
      women discontinued lovastatin more frequently than men because of adverse events.
      Overall, for the majority of drugs sex does not appear to be a factor that has to
      be taken into consideration when choosing a drug treatment. The available body of
      evidence, however, was limited in quality and quantity, confining the range and
      certainty of our conclusions.

PMID- 20689583
TI  - An open-label, randomised study of dihydroartemisinin-piperaquine versus
      artesunate-mefloquine for falciparum malaria in Asia.
AB  - BACKGROUND: The artemisinin-based combination treatment (ACT) of
      dihydroartemisinin (DHA) and piperaquine (PQP) is a promising novel anti-malarial
      drug effective against multi-drug resistant falciparum malaria. The aim of this
      study was to show non-inferiority of DHA/PQP vs. artesunate-mefloquine (AS+MQ) in
      Asia. METHODS AND FINDINGS: This was an open-label, randomised, non-inferiority,
      63-day follow-up study conducted in Thailand, Laos and India. Patients aged 3
      months to 65 years with Plasmodium falciparum mono-infection or mixed infection
      were randomised with an allocation ratio of 2:1 to a fixed-dose DHA/PQP
      combination tablet (adults: 40 mg/320 mg; children: 20 mg/160 [DOSAGE ERROR
      CORRECTED] mg; n = 769) or loose combination of AS+MQ (AS: 50 mg, MQ: 250 mg; n =
      381). The cumulative doses of study treatment over the 3 days were of about 6.75
      mg/kg of DHA and 54 mg/kg of PQP and about 12 mg/kg of AS and 25 mg/kg of MQ.
      Doses were rounded up to the nearest half tablet. The primary endpoint was day-63
      polymerase chain reaction (PCR) genotype-corrected cure rate. Results were 87.9%
      for DHA/PQP and 86.6% for AS+MQ in the intention-to-treat (ITT; 97.5% one-sided
      confidence interval, CI: >-2.87%), and 98.7% and 97.0%, respectively, in the per
      protocol population (97.5% CI: >-0.39%). No country effect was observed. Kaplan
      Meier estimates of proportions of patients with new infections on day 63
      (secondary endpoint) were significantly lower for DHA/PQP than AS+MQ: 22.7%
      versus 30.3% (p = 0.0042; ITT). Overall gametocyte prevalence (days 7 to 63;
      secondary endpoint), measured as person-gametocyte-weeks, was significantly
      higher for DHA/PQP than AS+MQ (10.15% versus 4.88%; p = 0.003; ITT). Fifteen
      serious adverse events were reported, 12 (1.6%) in DHA/PQP and three (0.8%) in
      AS+MQ, among which six (0.8%) were considered related to DHA/PQP and three (0.8%)
      to AS+MQ. CONCLUSIONS: DHA/PQP was a highly efficacious drug for P. falciparum
      malaria in areas where multidrug parasites are prevalent. The DHA/PQP combination
      can play an important role in the first-line treatment of uncomplicated
      falciparum malaria. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN81306618.

PMID- 20689585
TI  - Incidence of malaria and efficacy of combination antimalarial therapies over 4
      years in an urban cohort of Ugandan children.
AB  - BACKGROUND: Combination therapies are now recommended to treat uncomplicated
      malaria. We used a longitudinal design to assess the incidence of malaria and
      compare the efficacies of 3 combination regimens in Kampala, Uganda.
      METHODOLOGY/PRINCIPAL FINDINGS: Children aged 1-10 years were enrolled from
      randomly selected households in 2004-05 and 2007, and were followed at least
      monthly through 2008. Insecticide-treated bednets (ITNs) were provided in 2006.
      Children were randomized upon their first episode, and then treated for all
      episodes of uncomplicated malaria with amodiaquine/sulfadoxine-pyrimethamine
      (AQ/SP), artesunate/amodiaquine (AS/AQ), or artemether/lumefantrine (AL). Risks
      of parasitological failure were determined for each episode of uncomplicated
      malaria and clinical parameters were followed. A total of 690 children
      experienced 1464 episodes of malaria. 96% of these episodes were uncomplicated
      malaria and treated with study drugs; 94% were due to Plasmodium falciparum. The
      rank order of treatment efficacy was AL > AS/AQ > AQ/SP. Failure rates increased
      over time for AQ/SP, but not the artemisinin-based regimens. Over the 4-year
      course of the study the prevalence of asymptomatic parasitemia decreased from
      11.8% to 1.4%, the incidence of malaria decreased from 1.55 to 0.32 per person
      year, and the prevalence of anemia (hemoglobin <10 gm/dL) decreased from 5.9% to
      1.0%. No episodes of severe malaria (based on WHO criteria) and no deaths were
      seen. CONCLUSIONS/SIGNIFICANCE: With ready access to combination therapies and
      distribution of ITNs, responses were excellent for artemisinin-containing
      regimens, severe malaria was not seen, and the incidence of malaria and
      prevalence of parasitemia and anemia decreased steadily over time. TRIAL
      REGISTRATION: isrctn.org ISRCTN37517549.

PMID- 20689586
TI  - The chemopreventive effects of Protandim: modulation of p53 mitochondrial
      translocation and apoptosis during skin carcinogenesis.
AB  - Protandim, a well defined dietary combination of 5 well-established medicinal
      plants, is known to induce endogenous antioxidant enzymes, such as manganese
      superoxide dismutase (MnSOD). Our previous studies have shown through the
      induction of various antioxidant enzymes, products of oxidative damage can be
      decreased. In addition, we have shown that tumor multiplicity and incidence can
      be decreased through the dietary administration of Protandim in the two-stage
      skin carcinogenesis mouse model. It has been demonstrated that cell proliferation
      is accommodated by cell death during DMBA/TPA treatment in the two-stage skin
      carcinogenesis model. Therefore, we investigated the effects of the Protandim
      diet on apoptosis; and proposed a novel mechanism of chemoprevention utilized by
      the Protandim dietary combination. Interestingly, Protandim suppressed DMBA/TPA
      induced cutaneous apoptosis. Recently, more attention has been focused on
      transcription-independent mechanisms of the tumor suppressor, p53, that mediate
      apoptosis. It is known that cytoplasmic p53 rapidly translocates to the
      mitochondria in response to pro-apoptotic stress. Our results showed that
      Protandim suppressed the mitochondrial translocation of p53 and mitochondrial
      outer membrane proteins such as Bax. We examined the levels of p53 and MnSOD
      expression/activity in murine skin JB6 promotion sensitive (P+) and promotion
      resistant (P-) epidermal cells. Interestingly, p53 was induced only in P+ cells,
      not P- cells; whereas MnSOD is highly expressed in P- cells when compared to P+
      cells. In addition, wild-type p53 was transfected into JB6 P- cells. We found
      that the introduction of wild-type p53 promoted transformation in JB6 P- cells.
      Our results suggest that suppression of p53 and induction of MnSOD may play an
      important role in the tumor suppressive activity of Protandim.

PMID- 20689588
TI  - A modeling study on how cell division affects properties of epithelial tissues
      under isotropic growth.
AB  - Cell proliferation affects both cellular geometry and topology in a growing
      tissue, and hence rules for cell division are key to understanding multicellular
      development. Epithelial cell layers have for long times been used to investigate
      how cell proliferation leads to tissue-scale properties, including organism
      independent distributions of cell areas and number of neighbors. We use a cell
      based two-dimensional tissue growth model including mechanics to investigate how
      different cell division rules result in different statistical properties of the
      cells at the tissue level. We focus on isotropic growth and division rules
      suggested for plant cells, and compare the models with data from the Arabidopsis
      shoot. We find that several division rules can lead to the correct distribution
      of number of neighbors, as seen in recent studies. In addition we find that when
      also geometrical properties are taken into account other constraints on the cell
      division rules result. We find that division rules acting in favor of equally
      sized and symmetrically shaped daughter cells can best describe the statistical
      tissue properties.

PMID- 20689587
TI  - Parkin is protective against proteotoxic stress in a transgenic zebrafish model.
AB  - BACKGROUND: Mutations in the gene encoding the E3 ubiquitin ligase parkin (PARK2)
      are responsible for the majority of autosomal recessive parkinsonism. Similarly
      to other knockout mouse models of PD-associated genes, parkin knockout mice do
      not show a substantial neuropathological or behavioral phenotype, while loss of
      parkin in Drosophila melanogaster leads to a severe phenotype, including reduced
      lifespan, apoptotic flight muscle degeneration and male sterility. In order to
      study the function of parkin in more detail and to address possible differences
      in its role in different species, we chose Danio rerio as a different vertebrate
      model system. METHODOLOGY/PRINCIPAL FINDINGS: We first cloned zebrafish parkin to
      compare its biochemical and functional aspects with that of human parkin. By
      using an antisense knockdown strategy we generated a zebrafish model of parkin
      deficiency (knockdown efficiency between 50% and 60%) and found that the
      transient knockdown of parkin does not cause morphological or behavioral
      alterations. Specifically, we did not observe a loss of dopaminergic neurons in
      parkin-deficient zebrafish. In addition, we established transgenic zebrafish
      lines stably expressing parkin by using a Gal4/UAS-based bidirectional expression
      system. While parkin-deficient zebrafish are more vulnerable to proteotoxicity,
      increased parkin expression protected transgenic zebrafish from cell death
      induced by proteotoxic stress. CONCLUSIONS/SIGNIFICANCE: Similarly to human
      parkin, zebrafish parkin is a stress-responsive protein which protects cells from
      stress-induced cell death. Our transgenic zebrafish model is a novel tool to
      characterize the protective capacity of parkin in vivo.

PMID- 20689589
TI  - A conserved behavioral state barrier impedes transitions between anesthetic
      induced unconsciousness and wakefulness: evidence for neural inertia.
AB  - One major unanswered question in neuroscience is how the brain transitions
      between conscious and unconscious states. General anesthetics offer a
      controllable means to study these transitions. Induction of anesthesia is
      commonly attributed to drug-induced global modulation of neuronal function, while
      emergence from anesthesia has been thought to occur passively, paralleling
      elimination of the anesthetic from its sites in the central nervous system (CNS).
      If this were true, then CNS anesthetic concentrations on induction and emergence
      would be indistinguishable. By generating anesthetic dose-response data in both
      insects and mammals, we demonstrate that the forward and reverse paths through
      which anesthetic-induced unconsciousness arises and dissipates are not identical.
      Instead they exhibit hysteresis that is not fully explained by pharmacokinetics
      as previously thought. Single gene mutations that affect sleep-wake states are
      shown to collapse or widen anesthetic hysteresis without obvious confounding
      effects on volatile anesthetic uptake, distribution, or metabolism. We propose a
      fundamental and biologically conserved concept of neural inertia, a tendency of
      the CNS to resist behavioral state transitions between conscious and unconscious
      states. We demonstrate that such a barrier separates wakeful and anesthetized
      states for multiple anesthetics in both flies and mice, and argue that it
      contributes to the hysteresis observed when the brain transitions between
      conscious and unconscious states.

PMID- 20689590
TI  - Folding of matrix metalloproteinase-2 prevents endogenous generation of MHC class
      I restricted epitope.
AB  - BACKGROUND: We previously demonstrated that the matrix metalloproteinase-2 (MMP
      2) contained an antigenic peptide recognized by a CD8 T cell clone in the HLA
      A*0201 context. The presentation of this peptide on class I molecules by human
      melanoma cells required a cross-presentation mechanism. Surprisingly, the
      classical endogenous processing pathway did not process this MMP-2 epitope.
      METHODOLOGY/PRINCIPAL FINDINGS: By PCR directed mutagenesis we showed that
      disruption of a single disulfide bond induced MMP-2 epitope presentation. By
      Pulse-Chase experiment, we demonstrated that disulfide bonds stabilized MMP-2 and
      impeded its degradation. Finally, using drugs, we documented that mutated MMP-2
      epitope presentation used the proteasome and retrotranslocation complex.
      CONCLUSIONS/SIGNIFICANCE: These data appear crucial to us since they established
      the existence of a new inhibitory mechanism for the generation of a T cell
      epitope. In spite of MMP-2 classified as a self-antigen, the fact that cross
      presentation is the only way to present this MMP-2 epitope underlines the
      importance to target this type of antigen in immunotherapy protocols.

PMID- 20689591
TI  - Molecular evolution of the primate antiviral restriction factor tetherin.
AB  - BACKGROUND: Tetherin is a recently identified antiviral restriction factor that
      restricts HIV-1 particle release in the absence of the HIV-1 viral protein U
      (Vpu). It is reminiscent of APOBEC3G and TRIM5a that also antagonize HIV.
      APOBEC3G and TRIM5a have been demonstrated to evolve under pervasive positive
      selection throughout primate evolution, supporting the red-queen hypothesis.
      Therefore, one naturally presumes that Tetherin also evolves under pervasive
      positive selection throughout primate evolution and supports the red-queen
      hypothesis. Here, we performed a detailed evolutionary analysis to address this
      presumption. METHODOLOGY/PRINCIPAL FINDINGS: Results of non-synonymous and
      synonymous substitution rates reveal that Tetherin as a whole experiences neutral
      evolution rather than pervasive positive selection throughout primate evolution,
      as well as in non-primate mammal evolution. Sliding-window analyses show that the
      regions of the primate Tetherin that interact with viral proteins are under
      positive selection or relaxed purifying selection. In particular, the sites
      identified under positive selection generally focus on these regions, indicating
      that the main selective pressure acting on the primate Tetherin comes from virus
      infection. The branch-site model detected positive selection acting on the
      ancestral branch of the New World Monkey lineage, suggesting an episodic adaptive
      evolution. The positive selection was also found in duplicated Tetherins in
      ruminants. Moreover, there is no bias in the alterations of amino acids in the
      evolution of the primate Tetherin, implying that the primate Tetherin may retain
      broad spectrum of antiviral activity by maintaining structure stability.
      CONCLUSIONS/SIGNIFICANCE: These results conclude that the molecular evolution of
      Tetherin may be attributed to the host-virus arms race, supporting the Red Queen
      hypothesis, and Tetherin may be in an intermediate stage in transition from
      neutral to pervasive adaptive evolution.

PMID- 20689593
TI  - Prenatal stress exposure related to maternal bereavement and risk of childhood
      overweight.
AB  - BACKGROUND: It has been suggested that prenatal stress contributes to the risk of
      obesity later in life. In a population-based cohort study, we examined whether
      prenatal stress related to maternal bereavement during pregnancy was associated
      with the risk of overweight in offspring during school age. METHODOLOGY/PRINCIPAL
      FINDINGS: We followed 65,212 children born in Denmark from 1970-1989 who
      underwent health examinations from 7 to 13 years of age in public or private
      schools in Copenhagen. We identified 459 children as exposed to prenatal stress,
      defined by being born to mothers who were bereaved by death of a close family
      member from one year before pregnancy until birth of the child. We compared the
      prevalence of overweight between the exposed and the unexposed. Body mass index
      (BMI) values and prevalence of overweight were higher in the exposed children,
      but not significantly so until from 10 years of age and onwards, as compared with
      the unexposed children. For example, the adjusted odds ratio (OR) for overweight
      was 1.68 (95% confidence interval [CI] 1.08-2.61) at 12 years of age and 1.63
      (95% CI 1.00-2.61) at 13 years of age. The highest ORs were observed when the
      death occurred in the period from 6 to 0 month before pregnancy (OR 3.31, 95% CI
      1.71-6.42 at age 12, and OR 2.31, 95% CI 1.08-4.97 at age 13).
      CONCLUSIONS/SIGNIFICANCE: Our results suggest that severe pre-pregnancy stress is
      associated with an increased risk of overweight in the offspring in later
      childhood.

PMID- 20689592
TI  - CD25 appears non essential for human peripheral T(reg) maintenance in vivo.
AB  - BACKGROUND: IL-2 has been reported to be critical for peripheral T(reg) survival
      in mouse models. Here, we examined T(reg) maintenance in a series of paediatric
      liver transplant recipients who received basiliximab, a therapeutic anti-CD25
      monoclonal antibody. METHODOLOGY/PRINCIPAL FINDINGS: FoxP3+ CD4 T cells were
      analyzed by flow cytometry before liver grafting and more than 9 months later. We
      found that in vivo CD25 blockade did not lead to T(reg) depletion: the proportion
      of FoxP3+ cells among CD4 T cells and the level of FoxP3 expression were both
      unchanged. IL-2Rbeta expression was enhanced in FoxP3+ cells both before and
      after basiliximab treatment, while the level of IL-2Rgamma expression was similar
      in T(regs) and non-T(regs). No significant change in the weak or absent
      expression of IL-7Ralpha and IL-15Ralpha expression on FoxP3+ cells was observed.
      Although the proportion of FoxP3+ cells among CD4 T cells did not vary, food
      allergies occurred more rapidly after liver grafting in patients who received
      basiliximab, raising questions as to T(reg) functionality in vivo in the absence
      of functional CD25. CONCLUSIONS: CD25 appears non essential for human T(reg)
      peripheral maintenance in vivo. However, our results raise questions as to T(reg)
      functionality after therapeutic CD25 targeting.

PMID- 20689594
TI  - Electrical impedance of acupuncture meridians: the relevance of subcutaneous
      collagenous bands.
AB  - BACKGROUND: The scientific basis for acupuncture meridians is unknown. Past
      studies have suggested that acupuncture meridians are physiologically
      characterized by low electrical impedance and anatomically associated with
      connective tissue planes. We are interested in seeing whether acupuncture
      meridians are associated with lower electrical impedance and whether ultrasound
      derived measures--specifically echogenic collagenous bands--can account for these
      impedance differences. METHODS/RESULTS: In 28 healthy subjects, we assessed
      electrical impedance of skin and underlying subcutaneous connective tissue using
      a four needle-electrode approach. The impedances were obtained at 10 kHz and 100
      kHz frequencies and at three body sites - upper arm (Large Intestine meridian),
      thigh (Liver), and lower leg (Bladder). Meridian locations were determined by
      acupuncturists. Ultrasound images were obtained to characterize the anatomical
      features at each measured site. We found significantly reduced electrical
      impedance at the Large Intestine meridian compared to adjacent control for both
      frequencies. No significant decrease in impedance was found at the Liver or
      Bladder meridian. Greater subcutaneous echogenic densities were significantly
      associated with reduced impedances in both within-site (meridian vs. adjacent
      control) and between-site (arm vs. thigh vs. lower leg) analyses. This
      relationship remained significant in multivariable analyses which also accounted
      for gender, needle penetration depth, subcutaneous layer thickness, and other
      ultrasound-derived measures. CONCLUSION/SIGNIFICANCE: Collagenous bands,
      represented by increased ultrasound echogenicity, are significantly associated
      with lower electrical impedance and may account for reduced impedances previously
      reported at acupuncture meridians. This finding may provide important insights
      into the nature of acupuncture meridians and the relevance of collagen in
      bioelectrical measurements.

PMID- 20689595
TI  - Treatment of CoQ(10) deficient fibroblasts with ubiquinone, CoQ analogs, and
      vitamin C: time- and compound-dependent effects.
AB  - BACKGROUND: Coenzyme Q(10) (CoQ(10)) and its analogs are used therapeutically by
      virtue of their functions as electron carriers, antioxidant compounds, or both.
      However, published studies suggest that different ubiquinone analogs may produce
      divergent effects on oxidative phosphorylation and oxidative stress.
      METHODOLOGY/PRINCIPAL FINDINGS: To test these concepts, we have evaluated the
      effects of CoQ(10), coenzyme Q(2) (CoQ(2)), idebenone, and vitamin C on
      bioenergetics and oxidative stress in human skin fibroblasts with primary CoQ(10)
      deficiency. A final concentration of 5 microM of each compound was chosen to
      approximate the plasma concentration of CoQ(10) of patients treated with oral
      ubiquinone. CoQ(10) supplementation for one week but not for 24 hours doubled ATP
      levels and ATP/ADP ratio in CoQ(10) deficient fibroblasts therein normalizing the
      bioenergetics status of the cells. Other compounds did not affect cellular
      bioenergetics. In COQ2 mutant fibroblasts, increased superoxide anion production
      and oxidative stress-induced cell death were normalized by all supplements.
      CONCLUSIONS/SIGNIFICANCE: THESE RESULTS INDICATE THAT: 1) pharmacokinetics of
      CoQ(10) in reaching the mitochondrial respiratory chain is delayed; 2) short-tail
      ubiquinone analogs cannot replace CoQ(10) in the mitochondrial respiratory chain
      under conditions of CoQ(10) deficiency; and 3) oxidative stress and cell death
      can be counteracted by administration of lipophilic or hydrophilic antioxidants.
      The results of our in vitro experiments suggest that primary CoQ(10) deficiencies
      should be treated with CoQ(10) supplementation but not with short-tail ubiquinone
      analogs, such as idebenone or CoQ(2). Complementary administration of
      antioxidants with high bioavailability should be considered if oxidative stress
      is present.

PMID- 20689596
TI  - Epstein-Barr virus interferes with the amplification of IFNalpha secretion by
      activating suppressor of cytokine signaling 3 in primary human monocytes.
AB  - BACKGROUND: Epstein-Barr virus is recognized to cause lymphoproliferative
      disorders and is also associated with cancer. Evidence suggests that monocytes
      are likely to be involved in EBV pathogenesis, especially due to a number of
      cellular functions altered in EBV-infected monocytes, a process that may affect
      efficient host defense. Because type I interferons (IFNs) are crucial mediators
      of host defense against viruses, we investigated the effect of EBV infection on
      the IFNalpha pathway in primary human monocytes. METHODOLOGY/PRINCIPAL FINDINGS:
      Infection of monocytes with EBV induced IFNalpha secretion but inhibited the
      positive feedback loop for the amplification of IFNalpha. We showed that EBV
      infection induced the expression of suppressor of cytokine signaling 3 (SOCS3)
      and, to a lesser extent, SOCS1, two proteins known to interfere with the
      amplification of IFNalpha secretion mediated by the JAK/STAT signal transduction
      pathway. EBV infection correlated with a blockage in the activation of JAK/STAT
      pathway members and affected the level of phosphorylated IFN regulatory factor 7
      (IRF7). Depletion of SOCS3, but not SOCS1, by small interfering RNA (siRNA)
      abrogated the inhibitory effect of EBV on JAK/STAT pathway activation and
      significantly restored IFNalpha secretion. Finally, transfection of monocytes
      with the viral protein Zta caused the upregulation of SOCS3, an event that could
      not be recapitulated with mutated Zta. CONCLUSIONS/SIGNIFICANCE: We propose that
      EBV protein Zta activates SOCS3 protein as an immune escape mechanism that both
      suppresses optimal IFNalpha secretion by human monocytes and favors a state of
      type I IFN irresponsiveness in these cells. This immunomodulatory effect is
      important to better understand the aspects of the immune response to EBV.

PMID- 20689597
TI  - Genetic diversity among ancient Nordic populations.
AB  - Using established criteria for work with fossil DNA we have analysed
      mitochondrial DNA from 92 individuals from 18 locations in Denmark ranging in
      time from the Mesolithic to the Medieval Age. Unequivocal assignment of mtDNA
      haplotypes was possible for 56 of the ancient individuals; however, the success
      rate varied substantially between sites; the highest rates were obtained with
      untouched, freshly excavated material, whereas heavy handling, archeological
      preservation and storage for many years influenced the ability to obtain
      authentic endogenic DNA. While the nucleotide diversity at two locations was
      similar to that among extant Danes, the diversity at four sites was considerably
      higher. This supports previous observations for ancient Britons. The overall
      occurrence of haplogroups did not deviate from extant Scandinavians, however,
      haplogroup I was significantly more frequent among the ancient Danes (average
      13%) than among extant Danes and Scandinavians (approximately 2.5%) as well as
      among other ancient population samples reported. Haplogroup I could therefore
      have been an ancient Southern Scandinavian type "diluted" by later immigration
      events. Interestingly, the two Neolithic samples (4,200 YBP, Bell Beaker culture)
      that were typed were haplogroup U4 and U5a, respectively, and the single Bronze
      Age sample (3,300-3,500 YBP) was haplogroup U4. These two haplogroups have been
      associated with the Mesolithic populations of Central and Northern Europe.
      Therefore, at least for Southern Scandinavia, our findings do not support a
      possible replacement of a haplogroup U dominated hunter-gatherer population by a
      more haplogroup diverse Neolithic Culture.

PMID- 20689598
TI  - Oscillations by minimal bacterial suicide circuits reveal hidden facets of host
      circuit physiology.
AB  - Synthetic biology seeks to enable programmed control of cellular behavior though
      engineered biological systems. These systems typically consist of synthetic
      circuits that function inside, and interact with, complex host cells possessing
      pre-existing metabolic and regulatory networks. Nevertheless, while designing
      systems, a simple well-defined interface between the synthetic gene circuit and
      the host is frequently assumed. We describe the generation of robust but
      unexpected oscillations in the densities of bacterium Escherichia coli
      populations by simple synthetic suicide circuits containing quorum components and
      a lysis gene. Contrary to design expectations, oscillations required neither the
      quorum sensing genes (luxR and luxI) nor known regulatory elements in the P(luxI)
      promoter. Instead, oscillations were likely due to density-dependent plasmid
      amplification that established a population-level negative feedback. A
      mathematical model based on this mechanism captures the key characteristics of
      oscillations, and model predictions regarding perturbations to plasmid
      amplification were experimentally validated. Our results underscore the
      importance of plasmid copy number and potential impact of "hidden interactions"
      on the behavior of engineered gene circuits - a major challenge for standardizing
      biological parts. As synthetic biology grows as a discipline, increasing value
      may be derived from tools that enable the assessment of parts in their final
      context.

PMID- 20689599
TI  - New polynomial-based molecular descriptors with low degeneracy.
AB  - In this paper, we introduce a novel graph polynomial called the 'information
      polynomial' of a graph. This graph polynomial can be derived by using a
      probability distribution of the vertex set. By using the zeros of the obtained
      polynomial, we additionally define some novel spectral descriptors. Compared with
      those based on computing the ordinary characteristic polynomial of a graph, we
      perform a numerical study using real chemical databases. We obtain that the novel
      descriptors do have a high discrimination power.

PMID- 20689600
TI  - Burn injury reduces neutrophil directional migration speed in microfluidic
      devices.
AB  - Thermal injury triggers a fulminant inflammatory cascade that heralds shock, end
      organ failure, and ultimately sepsis and death. Emerging evidence points to a
      critical role for the innate immune system, and several studies had documented
      concurrent impairment in neutrophil chemotaxis with these post-burn inflammatory
      changes. While a few studies suggest that a link between neutrophil motility and
      patient mortality might exist, so far, cumbersome assays have prohibited
      exploration of the prognostic and diagnostic significance of chemotaxis after
      burn injury. To address this need, we developed a microfluidic device that is
      simple to operate and allows for precise and robust measurements of chemotaxis
      speed and persistence characteristics at single-cell resolution. Using this
      assay, we established a reference set of migration speed values for neutrophils
      from healthy subjects. Comparisons with samples from burn patients revealed
      impaired directional migration speed starting as early as 24 hours after burn
      injury, reaching a minimum at 72-120 hours, correlated to the size of the burn
      injury and potentially serving as an early indicator for concurrent infections.
      Further characterization of neutrophil chemotaxis using this new assay may have
      important diagnostic implications not only for burn patients but also for
      patients afflicted by other diseases that compromise neutrophil functions.

PMID- 20689602
TI  - Initial commitment to pre-exposure prophylaxis and circumcision for HIV
      prevention amongst Indian truck drivers.
AB  - Studies of HIV prevention interventions such as pre-exposure prophylaxis (PREP)
      and circumcision in India are limited. The present study sought to investigate
      Indian truck-drivers initial commitment to PREP and circumcision utilizing the
      AIDS Risk Reduction Model. Ninety truck-drivers completed an in-depth qualitative
      interview and provided a blood sample for HIV and HSV-2 testing. Truck-drivers
      exhibited low levels of initial commitment towards PREP and even lower for
      circumcision. However, potential leverage points for increasing commitment were
      realized in fear of infecting family rather than self, self-perceptions of risk,
      and for PREP focusing on cultural beliefs towards medication and physicians. Cost
      was a major barrier to both HIV prevention interventions. Despite these barriers,
      our findings suggest that the ARRM may be useful in identifying several leverage
      points that may be used by peers, health care providers and public health field
      workers to enhance initial commitment to novel HIV prevention interventions in
      India.

PMID- 20689603
TI  - Treated Colorectal Cancer: What is the Cost to Primary Care?
AB  - BACKGROUND: Colorectal cancer is the second commonest cause of cancer death and
      the cost to primary care has not been estimated. AIM: To determine the direct
      primary care costs of colorectal cancer care. DESIGN: Retrospective case note
      review. SETTING: Nottingham, United Kingdom. METHODS: We identified people with
      colorectal cancer between 1995 and 1998, from computerised pathology records.
      Colorectal cancer related resources consumed in primary care, from hospital
      discharge to death, were identified from retrospective notes review. Outcome
      measures were costs incurred by the General Practitioner (GP) and the total cost
      to primary care. We used multiple linear regression to identify predictors of
      cost. RESULTS: Of 416 people identified from pathology records, the median age at
      primary operation of the 135 (33%) people we selected was 74.2 (IQR 14.4) years,
      75 (56%) were male. The median GP cost was: Dukes A pound61.0 (IQR 516.2) and
      Dukes D pound936.2 (1196.2) p < 0.01. The geometric mean ratio found Dukes D
      cancers to be 10 times as costly as Dukes A. The median total cost was: Dukes A
      pound1038.3 (IQR 5090.6) and Dukes D pound1815.2 (2092.5) p = 0.06. Using
      multivariate analysis, Dukes stage was the most important predictor of GP costs.
      For total costs, the presence of a permanent stoma was the most predictive
      variable, followed by adjuvant therapy and advanced Dukes stage (Dukes C and D).
      CONCLUSIONS: Contrary to hospital based care costs, late stage disease (Dukes D)
      costs substantially more to general practice than any other stage. Stoma care
      products are the most costly prescribable item. Costs savings may be realised in
      primary care by screening detection of early stage colorectal cancers.

PMID- 20689601
TI  - Respiratory chain complexes in dynamic mitochondria display a patchy distribution
      in life cells.
AB  - BACKGROUND: Mitochondria, the main suppliers of cellular energy, are dynamic
      organelles that fuse and divide frequently. Constraining these processes impairs
      mitochondrial is closely linked to certain neurodegenerative diseases. It is
      proposed that functional mitochondrial dynamics allows the exchange of compounds
      thereby providing a rescue mechanism. METHODOLOGY/PRINCIPAL FINDINGS: The
      question discussed in this paper is whether fusion and fission of mitochondria in
      different cell lines result in re-localization of respiratory chain (RC)
      complexes and of the ATP synthase. This was addressed by fusing cells containing
      mitochondria with respiratory complexes labelled with different fluorescent
      proteins and resolving their time dependent re-localization in living cells. We
      found a complete reshuffling of RC complexes throughout the entire chondriome in
      single HeLa cells within 2-3 h by organelle fusion and fission. Polykaryons of
      fused cells completely re-mixed their RC complexes in 10-24 h in a progressive
      way. In contrast to the recently described homogeneous mixing of matrix-targeted
      proteins or outer membrane proteins, the distribution of RC complexes and ATP
      synthase in fused hybrid mitochondria, however, was not homogeneous but
      patterned. Thus, complete equilibration of respiratory chain complexes as
      integral inner mitochondrial membrane complexes is a slow process compared with
      matrix proteins probably limited by complete fusion. In co-expressing cells,
      complex II is more homogenously distributed than complex I and V, resp. Indeed,
      this result argues for higher mobility and less integration in supercomplexes.
      CONCLUSION/SIGNIFICANCE: Our results clearly demonstrate that mitochondrial
      fusion and fission dynamics favours the re-mixing of all RC complexes within the
      chondriome. This permanent mixing avoids a static situation with a fixed
      composition of RC complexes per mitochondrion.

PMID- 20689604
TI  - Recurrent pneumonia due to an appendiceal mucinous cystadenocarcinoma: a rare
      presentation of a rare malignancy.
AB  - Mucinous cystadenocarcinoma of the appendix is a rare malignancy. This is a
      report of a 74-year-old man who presented with recurrent pneumonia which turned
      out to be a postobstructive pneumonia complicating a large mucinous
      cystadenocarcinoma of the appendix with massive retroperitoneal and intrathoracic
      extension. Mucinous cystadenocarcinoma of the appendix is a low-grade malignancy
      characterized by expansive growth due to progressive accumulation of mucinous
      fluid produced by the cancer cells. The tendency of this tumor to expand
      massively is well demonstrated by this case. The unusual retroperitoneal location
      of appendix in this patient probably allowed the tumor to expand massively in the
      retroperitoneal space and the thoracic cavity. In addition to computed
      tomography, [(18)F]fluorodeoxyglucose positron emission tomography ((18)F-FDG
      PET) was used as an ancillary method for staging in this patient. The value of
      (18)F-FDG PET in the diagnosis of mucinous cystadenocarcinoma of the appendix has
      not been determined yet, but it might be promising. The most common presentation
      of this tumor is abdominal pain or a palpable ileocoecal mass. To the knowledge
      of the authors, this is the first report of an appendiceal mucinous
      cystadenocarcinoma with expansion into the thoracic cavity presenting with
      recurrent pneumonia.

PMID- 20689605
TI  - Treatment of early childhood medulloblastoma by postoperative chemotherapy alone
      a critical review.

PMID- 20689606
TI  - A Challenging Picture of Cancer-and Inflammation-Related Changes.
AB  - The authors describe a diagnostically challenging case where a patient with
      previous squamous cell carcinoma of the tonsil developed a putative second
      primary squamous cell carcinoma in the lung (stage IV with lung and bone
      metastases). During palliative chemotherapy several episodes of severe infection
      occurred, eventually resulting in abscess formation in the hip and brain. The
      dilemma of distinguishing between metastasis and abscess and the therapeutic
      implications are discussed.

PMID- 20689607
TI  - Anticancer conjugates and cocktails based on methotrexate and nucleoside
      synergism.
AB  - Conjugates of methotrexate (MTX) and the nucleoside analogs 3-azidodeoxythymidine
      (AZT), iododeoxyuridine (IUdR) and dideoxycytidine (ddC) linked using
      poly(ethyleneglycol) are presented. In vitro cytotoxicity assays of the
      conjugates against drug resistant ovarian cell line A2780/AD are preformed and
      comparisons made to such assays performed for unconjugated (cocktail) systems.
      All systems tested were inactive, or had low activity, at 24 h. After 72 hr
      incubation however, the cocktails of MTX and AZT, IUdR or ddC showed high
      cytotoxicity in the low nanomolar range. The conjugates were only very moderately
      active with IC(50) values in the [0.1 to 1.0 mM] range. Conjugation of the
      antifolate to the nucleoside analogs has it seems reduced the activity
      significantly when compared to a cocktail of the components, indicating a
      conjugate approach is unlikely to translate into success in vivo. The positive
      note comes from the observation that by combining two of the new conjugates,
      namely those based on MTX with IUdR or AZT, an IC50 at 24 hours of ~ [180 muM]
      was produced.

PMID- 20689608
TI  - Hospital costs of colorectal cancer care.
AB  - OBJECTIVE: In a hospital based setting, identify factors which influence the cost
      of colorectal cancer care? DESIGN: Retrospective case note review SETTING:
      Nottingham, United Kingdom PARTICIPANTS: 227 patients treated for colorectal
      cancer METHODS: Retrospective review of the hospital records provided the primary
      data for the costing study and included all CRC related resource consumption over
      the study period. RESULTS: Of 700 people identified, 227 (32%) sets of hospital
      notes were reviewed. The median age of the study group was 70.3 (IQR 11.3) years
      and there were 128 (56%) males. At two years, there was a significant difference
      in costs between Dukes D cancers ( pound3641) and the other stages ( pound3776
      Dukes A; pound4921 Dukes B). Using univariate and multivariate regression, the
      year of diagnosis, Dukes stage of disease, intensive nursing care, stoma
      requirements and recurrent disease all significantly affected the total cost of
      care. CONCLUSIONS: CRC remains costly with no significant difference in costs if
      diagnosed before compared to after 1992. Very early and very late stage cancers
      remain the least costly stage of cancers to treat. Other significant effectors of
      hospital costs were the site of cancer (rectal), intensive nursing care,
      recurrent disease and the need for a stoma.

PMID- 20689609
TI  - Photodynamic diagnosis for superficial bladder cancer: do all risk-groups profit
      equally from oncological and economic long-term results?
AB  - OBJECTIVE: Photodynamic diagnosis (PDD) of superficial bladder cancer decreases
      recurrence rates. We present oncological results of a randomized, prospective
      study, comparing transurethral resection (TUR) performed under conventional white
      light (WL) with PDD. The follow-up period is the longest reported to date. As
      costs might be reimbursed by prolonged recurrence-free survival in certain
      patients cost analysis in regard to risk-groups was performed. MATERIAL AND
      METHODS: Using chi-square test and log-rank test we compared recurrence rates of
      103 patients after WL-TUR and of 88 patients after PDD-TUR. Cost analysis was
      performed according to risk-groups of recurrence. RESULTS: Mean follow-up was 99
      months. Recurrence rate was 57% in WL vs. 28% in PDD (p < 0.001). Costs incurred
      by subsequent TUR averaged euro 2310 per WL patient vs. euro 713 per PDD patient.
      Savings per patient by PDD amounted to euro 1597. PDD costs were reimbursed in
      low, intermediate and high risk patients, respectively. CONCLUSIONS: PDD-TUR is
      significantly superior to conventional WL-TUR in terms of recurrence rate. While
      economic benefit is most prominent in intermediate risk patients, PDD related
      costs are reimbursed in all risk-groups.

PMID- 20689610
TI  - Endoscopic Ultrasound-Guided Fine Needle Aspiration (EUS-FNA) Diagnosis of
      Recurrent Anal Cancer After Chemoradiation and Negative Forceps Biopsies: A Case
      Report.
AB  - A 69-year-old woman with a history of uT2 N0 post-treated anal squamous cell
      cancer (SCC) presented for EUS for perianal pain. Two months prior, a digital
      rectal examination was significant for an indurated lesion on the left lateral
      rectal wall just proximal to the dentate line. A sigmoidoscopy revealed mild
      narrowing of the anal canal and an ulcerated friable mucosa in the same area. A
      biopsy demonstrated ulceration without malignancy. EUS showed a hypoechoic, non
      circumferential, left-sided distal rectal mass. EUS-FNA was performed. Cytology
      demonstrated poorly differentiated SCC. This was confirmed by subsequent surgical
      resection. While endoscopic biopsy of suspected anal recurrences is usually
      sufficient, histologic or cytologic confirmation are necessary, as radiation
      induced changes are difficult to differentiate from tumor recurrence. This case
      demonstrates that EUS-FNA is useful in surveillance of anal SCC when there is a
      high clinical suspicion of recurrence.

PMID- 20689611
TI  - Treatment of advanced non small cell lung cancer in routine care: a retrospective
      analysis of 212 consecutive patients treated in a community based oncology group
      practice.
AB  - Treatment outcome data generated in prospective trials are intrinsically biased
      due to necessary selection criteria. Therefore the results obtained may not
      reflect the actual impact of current treatment options for an unselected general
      population. We analysed the treatment modalities and the outcome in 212
      consecutive patients with non small cell lung cancer stages IIIB and IV who were
      seen in a community based oncology group practice between 6/1995 and 6/2006. 93
      presented with stage IIIB and 119 with stage IV. Chemotherapy was given to
      194/212 patients (92%), 114 patients (54%) received palliative radiation at one
      point during treatment. Treatment consisted of chemotherapy only in 86 patients
      (40%) and radiation only in 6 patients. 12 patients received best supportive care
      only. Patients with stage IIIB have survival rates at 12, 24 and 36 months of
      64%, 27% and 21% respectively and for patients with stage IV the survival rates
      at 12, 24 and 36 months are 40%, 19% and 11% respectively. The median survival
      for stages IIIB and IV is 16 and 11 months respectively. In a multivariate
      analysis incorporating the factors stage (IIIB vs. IV), age (<70 vs. >/=70 years)
      and performance status (WHO 0/1 vs. 2/3) only stage and performance status were
      independent factors for survival. These retrospective data concerning analysis of
      survival, response rates and toxicity in a community setting confirm published
      results of phase II-III studies and indicate that results generated in
      prospective trials can be transferred into routine care.

PMID- 20689612
TI  - Risk factors for renal cell cancer in a Japanese population.
AB  - The incidence of renal cell cancer has been increasing worldwide. Although the
      incidence of renal cell cancer in Japan is lower than the rates in the other
      industrialized countries, there is no doubt that it is increasing. In this paper,
      we would like to introduce the result of our studies, which evaluate the risk
      factors for renal cell cancer in Japan. Hypertension, diabetes mellitus, kidney
      diseases, fondness for fatty food and black tea showed an increased risk of renal
      cell carcinoma while an intake of starchy roots such as taro, sweet potato and
      potato reduced the risk of renal cell carcinoma. In Japan, however, drinking
      black tea may be a surrogate for westernized dietary habits while eating starchy
      roots may be a surrogate for traditional Japanese dietary habits. Further studies
      may be needed to evaluate risk factors for renal cell cancer because the number
      of renal cancer cases was small in our studies in spite of a large population
      based cohort study.

PMID- 20689614
TI  - A commentary on "risk factors for renal cell cancer in a Japanese population".
AB  - The well-written and researched article reported in Clinical Medicine: Oncology
      by Dr. Washio and Dr. Mori entitled "Risk factors for renal cell cancer in a
      Japanese population"1 makes evident the differences in incidence and mortality
      rates from renal cell carcinoma (RCC) between different populations and
      highlights the relevance of carrying out epidemiological studies, investigating
      additional risk factors which may explain the differences.

PMID- 20689613
TI  - Genomic heterogeneity of breast tumor pathogenesis.
AB  - Pathological grade is a useful prognostic factor for stratifying breast cancer
      patients into favorable (low-grade, well-differentiated tumors) and less
      favorable (high-grade, poorly-differentiated tumors) outcome groups. Under the
      current system of tumor grading, however, a large proportion of tumors are
      characterized as intermediate-grade, making determination of optimal treatments
      difficult. In an effort to increase objectivity in the pathological assessment of
      tumor grade, differences in chromosomal alterations and gene expression patterns
      have been characterized in low-grade, intermediate-grade, and high-grade disease.
      In this review, we outline molecular data supporting a linear model of
      progression from low-grade to high-grade carcinomas, as well as contradicting
      genetic data suggesting that low-grade and high-grade tumors develop
      independently. While debate regarding specific pathways of development continues,
      molecular data suggest that intermediate-grade tumors do not comprise an
      independent disease subtype, but represent clinical and molecular hybrids between
      low-grade and high-grade tumors. Finally, we discuss the clinical implications
      associated with different pathways of development, including a new clinical test
      to assign grade and guide treatment options.

PMID- 20689615
TI  - Gastric Adenocarcinoma: Is Computed Tomography (CT) Useful in Preoperative
      Staging?
AB  - BACKGROUND AND PURPOSE: Although multiple studies testing the accuracy of CT in
      the preoperative staging of gastric adenocarcinoma have been carried out, their
      results are controversial. Whilst some authors claim that CT is an accurate
      method for preoperatively staging gastric cancer, others have advocated the
      contrary. Because of this discrepancy we have retrospectively reviewed
      preoperative CT findings compared with histopathological results in patients with
      gastric adenocarcinoma. PATIENTS AND METHODS: Seventy-two patients diagnosed with
      gastric cancer who underwent potentially curative surgery and preoperative
      staging CT of quality were included in the study. The size, gastric wall
      thickening, presence of lymphadenopathy, adjacent organ invasion and location of
      the gastric mass was recorded. Early tumors (T1 and T2) and more advanced tumors
      (T3 and T4) were grouped together. CT staging was correlated with the final
      histopathological stage (TNM). The global results were expressed as sensitivity,
      specificity, positive predictive value (PPV) and negative predictive value (NPV).
      RESULTS: Seventy-two cases were included with fifty-five being male and a median
      age of 67 years (range 33-91). CT correctly identified the location of the tumor
      in 56 (53% antropyloric, 18% subcardial). Median time from CT scan to surgery was
      fourteen days (range 2-49). In T detection: T1/T2 and T3/T4 with sensitivity of
      70% and 61%. Lymph node involvement: Sensitivity 49%. Overstaged in 47%
      Understaged in 75%. Specificity of 53%. Nine patients with colon-mesocolon (5
      patients) and pancreas (4 patients) invasion. Sensitivity 44% and specificity
      96%. CONCLUSION: Spiral CT is not an accurate method in predicting preoperative
      stages in gastric cancer.

PMID- 20689616
TI  - The metastasectomy and timing of pulmonary metastases on the outcome of
      osteosarcoma patients.
AB  - BACKGROUND: The author intended to clarify the therapeutic effect and prognostic
      factors of metastasectomy and timing of pulmonary metastases in osteosarcoma
      patents. METHODS: Data was obtained retrospectively on all consecutive
      osteosarcoma patients from 1985 to 2005 in author's institute. Fifty-two patients
      with pulmonary nodules were identified, including 24 patients undergoing
      pulmonary metastasectomy treatment. These patients were categorized into four
      groups: group 1, patients with lung metastases at the initial presentation; group
      2, lung metastases identified during the period of pre-operative chemotherapy;
      group 3, lung metastases identified during period of the post-operative che
      motherapy; group 4, lung metastases identified after therapy for the primary
      osteosarcoma completed. RESULTS: In our study, the 2-, 3-, and 5-year overall
      survival rates for 52 patients were 49%, 39% and 20%. The 2-year overall survival
      rates were 18% for group 1, 32% for group 3, and 70% for group 4 (p < 0.001). The
      5-year overall survival rate was 34% for group 4. Patients who underwent
      metastesectomy showed a better survival outcome as compared with the patients not
      undergoing metastasectomy (p = 0.003). The 2-year and 5-year overall survival
      rates of only one lung metastatic nodule were 62% and 50%, and for initially
      multiple lung metastatic nodules, 45% and 5%, respectively. In addition, the
      patients presented with lung metastases had a worse prognosis as compared with
      those without initial lung metastases (p = 0.0001). CONCLUSIONS: The patients
      having single metastatic nodule showed a better prognosis than those with
      multiple lung nodules. Furthermore, those patients who underwent metastasectomy
      survived longer than those not undergoing metastasectomy. Patients who had late
      metastases after complete chemotherapy had a better prognosis; whereas those who
      had metastases identified at the initial presentation predicted a poor prognosis.

PMID- 20689617
TI  - Adjuvant Chemotherapy for Patients with Stage III Colon Cancer: Results from a
      CDC-NPCR Patterns of Care Study.
AB  - OBJECTIVE: To evaluate adjuvant chemotherapy use for Stage III colon cancer.
      METHODS: This analysis included 973 patients with surgically treated stage III
      colon cancer. Socioeconomic information from the 2000 census was linked to
      patients' residential census tracts. Vital status through 12/31/02 was obtained
      from medical records and linkage to state vital statistics files and the National
      Death Index. RESULTS: Adjuvant chemotherapy was received by 67%. Treatment varied
      by state of residence, with Colorado, Rhode Island and New York residents more
      likely to receive chemotherapy than Louisiana residents. Older age, increasing
      comorbidities, divorced/widowed marital status, and residence in lower education
      areas or non-working class neighborhoods were associated with lower chemotherapy
      use. Survival varied by state but after adjustment for sex, sociodemographic and
      health factors, was significantly higher only for California and Rhode Island.
      Older age and lower educational attainment were associated with lower survival.
      Chemotherapy was protective for all comorbidity groups. CONCLUSION: Although
      adjuvant chemotherapy for Stage III colon cancer improves survival, some patients
      did not receive standard of care, demonstrating the need for cancer treatment
      surveillance. Interstate differences likely resulted from differences in local
      practice patterns, acceptance of treatment, and access.

PMID- 20689618
TI  - THE VIRTUAL INSTRUMENT: SUPPORT FOR GRID-ENABLED MCELL SIMULATIONS.
AB  - Ensembles of widely distributed, heterogeneous resources, or Grids, have emerged
      as popular platforms for large-scale scientific applications. In this paper we
      present the Virtual Instrument project, which provides an integrated application
      execution environment that enables end-users to run and interact with running
      scientific simulations on Grids. This work is performed in the specific context
      of MCell, a computational biology application. While MCell provides the basis for
      running simulations, its capabilities are currently limited in terms of scale,
      ease-of-use, and interactivity. These limitations preclude usage scenarios that
      are critical for scientific advances. Our goal is to create a scientific "Virtual
      Instrument" from MCell by allowing its users to transparently access Grid
      resources while being able to steer running simulations. In this paper, we
      motivate the Virtual Instrument project and discuss a number of relevant issues
      and accomplishments in the area of Grid software development and application
      scheduling. We then describe our software design and report on the current
      implementation. We verify and evaluate our design via experiments with MCell on a
      real-world Grid testbed.

PMID- 20689619
TI  - Spatio-temporal dynamics in fMRI recordings revealed with complex independent
      component analysis.
AB  - Independent component analysis (ICA) of functional magnetic resonance imaging
      (fMRI) data is commonly carried out under the assumption that each source may be
      represented as a spatially fixed pattern of activation, which leads to the
      instantaneous mixing model. To allow modeling patterns of spatio-temporal
      dynamics, in particular, the flow of oxygenated blood, we have developed a
      convolutive ICA approach: spatial complex ICA applied to frequency-domain fMRI
      data. In several frequency-bands, we identify components pertaining to activity
      in primary visual cortex (V1) and blood supply vessels. One such component,
      obtained in the 0.10 Hz band, is analyzed in detail and found to likely reflect
      flow of oxygenated blood in V1.

PMID- 20689620
TI  - Elastic membrane that undergoes mechanical deformation enhances osteoblast
      cellular attachment and proliferation.
AB  - The main objective of this paper was to investigate the effect of transmission of
      force on bone cells that were attached to a deformable membrane. We
      functionalized a silastic membrane that measured 0.005 inches thickness and
      coated it with an extra cellular matrix (ECM) protein, fibronectin (FN). MC3T3-E1
      osteoblast-like cells were cultured on the functionalized FN-coated membrane
      after which cell attachment and proliferation were evaluated. We observed an
      immediate attachment and proliferation of the bone cells on the functionalized
      membrane coated with FN, after 24 hours. Upon application of a mechanical force
      to cells cultured on the functionalized silicone membrane in the form of a
      dynamic equibiaxial strain, 2% magnitude; at 1-Hz frequency for 2 h, the
      osteoblast cells elicited slightly elevated phalloidin fluorescence, suggesting
      that there was reorganization of the cytoskeleton. We concluded from this
      preliminary data obtained that the engineered surface transduced applied
      mechanical forces directly to the adherent osteoblast cells via integrin binding
      tripeptide receptors, present in the FN molecules, resulting in the enhanced
      cellular attachment and proliferation.

PMID- 20689622
TI  - C1 esterase inhibitor (human).

PMID- 20689621
TI  - Effect of decellularization protocol on the mechanical behavior of porcine
      descending aorta.
AB  - Enzymatic-detergent decellularization treatments may use a combination of
      chemical reagents to reduce vascular tissue to sterilized scaffolds, which may be
      seeded with endothelial cells and implanted with a low risk of rejection.
      However, these chemicals may alter the mechanical properties of the native tissue
      and contribute to graft compliance mismatch. Uniaxial tensile data obtained from
      native and decellularized longitudinal aortic tissue samples was analyzed in
      terms of engineering stress and fit to a modified form of the Yeoh rubber model.
      One decellularization protocol used SDS, while the other two used TritonX-100,
      RNase-A, and DNase-I in combination with EDTA or sodium-deoxycholate. Statistical
      significance of Yeoh model parameters was determined by paired t-test analysis.
      The TritonX-100/EDTA and 0.075% SDS treatments resulted in relatively variable
      mechanical changes and did not effectively lyse VSMCs in aortic tissue. The
      TritonX-100/sodium-deoxycholate treatment effectively lysed VSMCs and was
      characterized by less variability in mechanical behavior. The data suggests a
      TritonX-100/sodium-deoxycholate treatment is a more effective option than TritonX
      100/EDTA and SDS treatments for the preparation of aortic xenografts and
      allografts because it effectively lyses VSMCs and is the least likely treatment,
      among those considered, to promote a decrease in mechanical compliance.

PMID- 20689623
TI  - Pharma twitters cautiously before advertising guidelines are released.

PMID- 20689624
TI  - Technology, vigilance, and blood transfusions: how u.s. Hospitals and the federal
      government are working to reduce adverse events.

PMID- 20689625
TI  - Value of inhaled corticosteroid therapy in long-term asthma management.
AB  - Asthma, which affects more than 22 million people in the U.S. every year, poses a
      significant clinical and economic burden to our health care system. Patients,
      health care practitioners, and payers require a variety of resources to ensure
      optimal disease management and positive clinical outcomes while also managing
      costs. In addition, decision makers in health care must determine the most
      appropriate and cost-efficient therapy or class of agents to achieve asthma
      control. As such, payers rely on evidence-based medicine, including guidelines to
      determine the right therapy for the right patient.Inhaled corticosteroid (ICS)
      therapy plays a critical role in the management of mild-to-moderate persistent
      asthma. Despite national treatment guidelines that cite ICS therapy as the most
      effective and safest long-term treatment option for persistent asthma, ICS
      monotherapy continues to be underused. One retrospective claims study found that
      55.2% of children with mild-to-moderate asthma received prescriptions for
      combination therapy (ICS and long-acting beta-agonists) as initial controller
      treatment. This practice is contrary to national treatment guidelines, which
      recommend a step-therapy approach. These prescribing patterns result in higher
      pharmacy costs, do not always ensure control of symptoms, and sometimes expose
      patients to potential safety risks.This article addresses the importance of ICS
      therapy in the treatment of mild-to-moderate asthma, as advocated by the National
      Asthma Education and Prevention Program (NAEPP) Expert Panel Report 3 guidelines;
      the role of small airway disease in asthma pathophysiology; and the clinical and
      economic benefits of ICS therapy.

PMID- 20689626
TI  - Overview of drugs used for epilepsy and seizures: etiology, diagnosis, and
      treatment.

PMID- 20689627
TI  - Topiramate Treatment of Essential Tremor in a Patient with Cognitive Deficits.
AB  - This case report demonstrates a satisfying response to topiramate in a 79-year
      old patient with disabling essential tremor in whom propranolol as well as
      primidone had to be discontinued due to severe side effects. After 28 months of
      topiramate treatment, a clear decline in Mini Mental State Examination (MMSE)
      could be observed, stressing the use of care in prescribing topiramate in elderly
      patients.

PMID- 20689628
TI  - Cerebrospinal Fluid Biomarkers in Diagnosing Alzheimer's Disease in Clinical
      Practice: An Illustration with 3 Case Reports.
AB  - Analysis of the brain specific biomarkers amyloid beta(42) (Abeta(42)) and total
      tau (t-tau) protein in cerebrospinal fluid (CSF) has a sensitivity and
      specificity of more than 85% for differentiating Alzheimer's Disease (AD) from
      non-demented controls. International guidelines are contradictory in their advice
      on the use of CSF biomarkers in AD diagnostics, resulting in a lack of
      consistency in clinical practice. We present three case reports that illustrate
      clinical practice according to the Dutch and European guidelines and portray the
      value of CSF biomarker analysis as an add-on diagnostic to the standard
      diagnostic workup for AD.

PMID- 20689629
TI  - Progressive Stroke-Like Symptoms in a Patient with Sporadic Creutzfeldt-Jakob
      Disease.
AB  - Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare neurodegenerative disorder in
      which accumulation of a pathogenic isoform of prion protein (PrP(Sc)) induces
      neuronal damage with distinct pathologic features. The prognosis of sCJD is
      devastating: rapid clinical decline is followed by death generally within months
      after onset of symptoms. The classic clinical manifestations of sCJD are rapidly
      progressing dementia, myoclonus, and ataxia. However, the spectrum of clinical
      features can vary considerably. We describe a definite, neuropathologically
      verified sCJD in a 67-year-old woman who initially presented with progressive
      stroke-like symptoms: left-sided hemiparesis and ataxia within a few days. The
      initial brain magnetic resonance imaging (MRI) showed bilateral cortical
      hyperintensity on diffusion-weighted sequences (DWI) resembling multiple ischemic
      lesions. Despite anticoagulation with low-molecular-weight heparin, the patient
      deteriorated rapidly, became dysphagic and bedridden with myoclonic jerks on her
      left side extremities correlating with intermittent high-amplitude epileptiform
      discharges on electroencephalography (EEG). Basal ganglia hyperintense signal
      changes in addition to cortical ribboning were seen in DWI images of a follow-up
      MRI. Repeated EEG recordings showed an evolution to periodic sharp wave
      complexes. Protein 14-3-3 was positive in her cerebrospinal fluid specimen, in
      addition to an abnormally high total tau level. In the terminal stage the patient
      was in an akinetic, mutistic state with deteriorating consciousness. She died 19
      days after admission to the hospital. Neuropathologic investigation corroborated
      the clinical diagnosis of sCJD with spongiform degeneration and
      immunohistochemical demonstration of the deposition of pathologic PrP(Sc).

PMID- 20689630
TI  - Evolution of Callosal and Cortical Lesions on MRI in Marchiafava-Bignami Disease.
AB  - We report on serial MRI findings of cerebral lesions in a 55-year-old man with
      severe Marchiafava-Bignami disease (MBD). The first MRI change on fluid
      attenuated inversion recovery images was hyperintensity in the genu of the corpus
      callosum and in the frontoparietal cortex. Following this change, a splenial
      lesion appeared. The first MRI change in the genu of the corpus callosum was not
      associated with a change in diffusion on diffusion-weighted MRI imaging,
      suggesting a pathological change involving vasogenic edema. Development of
      cortical lesions in the initial stage confirms that cortical lesions result from
      the primary pathogenetic process induced by alcoholic intoxication and
      malnutrition in MBD.

PMID- 20689631
TI  - Transesophageal Echocardiographically-Confirmed Pulmonary Vein Thrombosis in
      Association with Posterior Circulation Infarction.
AB  - Pulmonary venous thromboembolism has only been identified as a cause of stroke
      with pulmonary arteriovenous malformations/fistulae, pulmonary neoplasia,
      transplantation or lobectomy, and following percutaneous radiofrequency ablation
      of pulmonary vein ostia in patients with atrial fibrillation. A 59-year-old man
      presented with a posterior circulation ischemic stroke. 'Unheralded' pulmonary
      vein thrombosis was identified on transesophageal echocardiography as the likely
      etiology. He had no further cerebrovascular events after intensifying
      antithrombotic therapy. Twenty-eight months after initial presentation, he was
      diagnosed with metastatic pancreatic adenocarcinoma and died 3 months later. This
      report illustrates the importance of doing transesophageal echocardiography in
      presumed 'cardioembolic' stroke, and that potential 'pulmonary venous
      thromboembolic' stroke may occur in patients without traditional risk factors for
      venous thromboembolism. Consideration should be given to screening such patients
      for occult malignancy.

PMID- 20689632
TI  - Spinal Epidural Hematoma as a Complication of Intravenous Thrombolysis in an
      Acute Ischemic Stroke Patient.
AB  - An 80-year-old white male suffered a stroke, fell to the floor, and suffered
      acute right hemiparesis and facial palsy. After an intravenous alteplase infusion
      2.5 h later, the patient first complained of numbness in his right arm, then neck
      pain, followed by left leg numbness and slowly progressing paraparesis. MRI of
      the spine demonstrated an acute spinal dorsal epidural hematoma extending from
      the C6 to the T6 level; 12 h later, he underwent hematoma evacuation and
      laminectomy. Three months after surgery, the patient was paraplegic with moderate
      sensory loss below mamillary level. Acute ischemic stroke is often associated
      with a sudden fall, which, after thrombolysis, may result in unusual hemorrhagic
      complications.

PMID- 20689633
TI  - Malignant Acanthosis Nigricans Associated with Ovarian Cancer.
AB  - Malignant acanthosis nigricans is a cutaneous eruption characterized by symmetric
      hyperpigmented hyperkeratosis, dermal papillomatosis, and mucosal involvement
      associated with internal malignancies. Tripe palms refers to a characteristic
      velvety thickening of the palms, with exaggeration of normal skin markings. We
      present the second case of ovarian cancer in association with two coexisting
      paraneoplastic dermatoses occurring in a 57-year-old Korean female. The presence
      of acanthosis nigricans in conjunction with tripe palms in a female patient is
      highly suggestive of an internal malignancy including an ovarian cancer and
      demands an extensive search for the hidden ovarian cancer.

PMID- 20689634
TI  - A Case of Orbital Xanthogranuloma Treated by Surgical Excision.
AB  - Orbital xanthogranuloma is an uncommon tumor. It is usually associated with a
      systemic or hematological disease. This report presents a rare case of orbital
      xanthogranuloma associated with heart disease and thrombocytopenia. A 52-year-old
      female presented with a bilateral periorbital subcutaneous tumor that had existed
      for 3 years. Although immunoglobulin levels were within the normal limits,
      thrombocytopenia, slight anemia and increased levels of C-reactive protein and
      alkaline phosphatase were observed. The mass was excised successfully. The malar
      flap elevation technique made it easy to approach the periorbital subcutaneous
      mass. A histopathological study led to a diagnosis of xanthogranuloma based on
      the presence of infiltration of histiocytes and Touton-type giant cells.

PMID- 20689635
TI  - A Case of Multiple Pilosebaceous Cysts.
AB  - Multiple pilosebaceous cysts include the entities of steatocystoma multiplex and
      eruptive vellus hair cysts (EVHCs). Multiple pilosebaceous cysts are proposed to
      be one entity originating in the pilosebaceous duct, since steatocystoma
      multiplex and EVHCs are frequently present concomitantly and are caused by a
      cystic change in the same pilosebaceous duct. Here, we describe a patient with
      yellowish papules, 3-8 mm in diameter, on the neck and skin-colored or light
      brown papules, 1-3 mm in diameter, on the neck, chest and upper abdomen. The
      smaller cysts were histopathologically diagnosed as EVHCs. The larger cysts had
      both features of EVHCs and steatocystoma multiplex. Therefore, a diagnosis of
      these lesions was made as multiple pilosebaceous cysts. Our case supports the
      proposition that multiple pilosebaceous cysts are a more appropriate diagnosis
      than the terms of EVHCs and steatocystoma multiplex.

PMID- 20689636
TI  - Successful Intervention for Pressure Ulcer by Nutrition Support Team: A Case
      Report.
AB  - A 23-year-old woman with heart failure developed pressure ulcer on her sacral
      area due to a long-term bed rest and impaired hemodynamics. The ulcer improved
      only slightly after 2 months with povidone-iodine sugar ointment because of
      severe nausea and anorexia. Then, the nutrition support team (NST) started
      intervention and estimated the patient's malnutrition from her body weight (30.1
      kg), body mass index (BMI) (13.9), triceps skinfold thickness (TSF) (3.5 mm), arm
      circumference (AC) (17.2 cm) and serum albumin (2.6 g/dl). The NST administrated
      an enteral nutrition formula through a nasogastric tube and tried to provide
      meals according to the patient's taste. Although DESIGN score improved to 7
      (DESIGN: d2e1s2i1g1n0 = 7) 2 months later, severe nausea prevented the patient
      from taking any food perorally. However, after nasogastric decannulation, her
      appetite improved and 1 month later her body weight increased to 32.8 kg, her BMI
      to 15.2, TSF to 7.5 mm, AC to 19.7 cm and serum albumin to 4.1 g/dl, and the
      wound completely healed.

PMID- 20689637
TI  - Perceptual judgment and saccadic behavior in a spatial distortion with briefly
      presented stimuli.
AB  - When observers are asked to localize the peripheral position of a small probe
      with respect to the mid-position of a spatially extended comparison stimulus,
      they tend to judge the probe as being more peripheral than the mid-position of
      the comparison stimulus. This relative mislocalization seems to emerge from
      differences in absolute localization, that is the comparison stimulus is
      localized more towards the fovea than the probe. The present study compared
      saccadic behaviour and relative localization judgements in three experiments and
      determined the quantitative relationship between both measures. The results
      showed corresponding effects in localization errors and saccadic behaviour.
      Moreover, it was possible to estimate the amount of the relative mislocalization
      by means of the saccadic amplitude.

PMID- 20689638
TI  - Faster decline of pitch memory over time in congenital amusia.
AB  - Congenital amusia (amusia, hereafter) is a developmental disorder that impacts
      negatively on the perception of music. Psychophysical testing suggests that
      individuals with amusia have above average thresholds for detection of pitch
      change and pitch direction discrimination; however, a low-level auditory
      perceptual problem cannot completely explain the disorder, since discrimination
      of melodies is also impaired when the constituent intervals are suprathreshold
      for perception. The aim of the present study was to test pitch memory as a
      function of (a) time and (b) tonal interference, in order to determine whether
      pitch traces are inherently weaker in amusic individuals. Memory for the pitch of
      single tones was compared using two versions of a paradigm developed by Deutsch
      (1970a). In both tasks, participants compared the pitch of a standard (S) versus
      a comparison (C) tone. In the time task, the S and C tones were presented,
      separated in time by 0, 1, 5, 10, and 15 s (blocked presentation). In the
      interference task, the S and C tones were presented with a fixed time interval (5
      s) but with a variable number of irrelevant tones in between 0, 2, 4, 6, and 8
      tones (blocked presentation). In the time task, control performance remained high
      for all time intervals, but amusics showed a performance decrement over time. In
      the interference task, controls and amusics showed a similar performance
      decrement with increasing number of irrelevant tones. Overall, the results
      suggest that the pitch representations of amusic individuals are less stable and
      more prone to decay than those of matched non-amusic individuals.

PMID- 20689639
TI  - Configural and featural processing in humans with congenital prosopagnosia.
AB  - Prosopagnosia describes the failure to recognize faces, a deficiency that can be
      devastating in social interactions. Cases of acquired prosopagnosia have often
      been described over the last century. In recent years, more and more cases of
      congenital prosopagnosia (CP) have been reported. In the present study we tried
      to determine possible cognitive characteristics of this impairment. We used
      scrambled and blurred images of faces, houses, and sugar bowls to separate
      featural processing strategies from configural processing strategies. This served
      to investigate whether congenital prosopagnosia results from process-specific
      deficiencies, or whether it is a face-specific impairment. Using a delayed
      matching paradigm, 6 individuals with CP and 6 matched healthy controls indicated
      whether an intact test stimulus was the same identity as a previously presented
      scrambled or blurred cue stimulus. Analyses of d values indicated that congenital
      prosopagnosia is a face-specific deficit, but that this shortcoming is
      particularly pronounced for processing configural facial information.

PMID- 20689640
TI  - Eltrombopag--a novel approach for the treatment of chronic immune
      thrombocytopenic purpura: review and safety considerations.
AB  - Eltrombopag is one of a number of novel agents recently developed for use in the
      treatment of patients with immune thrombocytopenia (ITP). Rather than preventing
      destruction of platelets, these agents increase the production of platelets,
      presumably overwhelming the immune system resulting in normal platelet counts in
      individuals refractory to or dependent on other therapies. These treatments are
      well tolerated and in randomized controlled trials show an improvement in
      platelet counts and a reduction in bleeding in refractory patients. This article
      summarizes the development of this new class of drug and evaluates the safety and
      efficacy of eltrombopag in patients with ITP.

PMID- 20689643
TI  - Photo-acoustic concave transmitter for generating high frequency focused
      ultrasound.
AB  - We present a photo-acoustic concave transmitter to generate and subsequently
      focus high frequency ultrasound. Owing to a short time-duration of pulse laser
      beam, high frequency acoustic waves and tight focusing can be easily achieved.
      The transmitter consists of a light-absorbing film coated on a concave spherical
      structure. For detection, we used an optical microring ultrasound detector
      capable of covering a broadband and high frequency spectrum of photo-acoustic
      source. A spot width of ~44 MUm was obtained at the focal plane. As the finite
      size and the specific shape of the microring cause a geometrical effect on the
      detection process, especially for high frequency components, we performed a 2-D
      spatial signal processing to remove this effect and extract a pure pressure
      distribution. The aperture for acoustic focusing could be optically controlled by
      changing the size of pulse laser beam.

PMID- 20689641
TI  - Roflumilast: first phosphodiesterase 4 inhibitor approved for treatment of COPD.
AB  - In April 2010, the European Medicines Agency Committee for Medicinal Products for
      Human Use recommended approval of roflumilast, a selective phosphodiesterase 4
      inhibitor, for the "maintenance treatment of severe chronic obstructive pulmonary
      disease (COPD, FEV(1) postbronchodilator less than 50% predicted) associated with
      chronic bronchitis in adult patients with a history of frequent exacerbations as
      add-on to bronchodilator treatment". This decision was based, in part, on the
      results of several large, international, multicenter, randomized, placebo
      controlled trials of either six or 12 months' duration that had been undertaken
      in COPD patients. Roflumilast 500 mug daily improved lung function and reduced
      exacerbations in patients with more severe COPD, especially those with chronic
      bronchitis, frequent exacerbations, or who required frequent rescue inhaler
      therapy in the placebo-controlled trials. It also improved lung function and
      reduced exacerbations in patients with moderately severe COPD treated with
      salmeterol or tiotropium. Advantages of roflumilast over inhaler therapy are that
      it is an oral tablet and only needs to be taken once daily. While taking
      roflumilast, the most common adverse effects patients experienced were
      gastrointestinal upset and headache. Weight loss, averaging 2.2 kg, occurred in
      patients treated with roflumilast. Patients taking roflumilast were more likely
      to drop out of the trials than patients in the control groups. Patients who
      discontinued therapy usually did so during the first few weeks and were more
      likely to have experienced gastrointestinal side effects. Roflumilast is the
      first selective phosphodiesterase 4 inhibitor and will offer physicians another
      treatment option for patients with more severe COPD.

PMID- 20689644
TI  - Generalized Functional Linear Models with Semiparametric Single-Index
      Interactions.
AB  - We introduce a new class of functional generalized linear models, where the
      response is a scalar and some of the covariates are functional. We assume that
      the response depends on multiple covariates, a finite number of latent features
      in the functional predictor, and interaction between the two. To achieve
      parsimony, the interaction between the multiple covariates and the functional
      predictor is modeled semiparametrically with a single-index structure. We propose
      a two step estimation procedure based on local estimating equations, and
      investigate two situations: (a) when the basis functions are pre-determined,
      e.g., Fourier or wavelet basis functions and the functional features of interest
      are known; and (b) when the basis functions are data driven, such as with
      functional principal components. Asymptotic properties are developed. Notably, we
      show that when the functional features are data driven, the parameter estimates
      have an increased asymptotic variance, due to the estimation error of the basis
      functions. Our methods are illustrated with a simulation study and applied to an
      empirical data set, where a previously unknown interaction is detected. Technical
      proofs of our theoretical results are provided in the online supplemental
      materials.

PMID- 20689645
TI  - Photoacoustic correlation technique for low-speed flow measurement.
AB  - A photoacoustic correlation spectroscopy (PACS) technique was proposed for the
      first time. This technique is inspired by its optical counterpart-the
      fluorescence correlation spectroscopy (FCS), which is widely used in the
      characterization of the dynamics of fluorescent species. The fluorescence
      intensity is measured in FCS while the acoustic signals are detected in PACS. To
      proof of concept, we demonstrated the flow measurement of light-absorbing beads
      probed by a pulsed laser. A PACS system with temporal resolution of 0.8 sec was
      built. Polymer microring resonators were used to detect the photoacoustic
      signals, which were then signal processed and used to obtain the autocorrelation
      curves. Flow speeds ranging from 249 to 15.1 MUm/s with corresponding flow time
      from 4.42 to 72.5 sec were measured. The capability of low-speed flow measurement
      can potentially be used for detecting blood flow in relatively deep capillaries
      in biological tissues. Moreover, similar to FCS, PACS may have many potential
      applications in studying the dynamics of photoacoustic beads.

PMID- 20689646
TI  - Novel Actions of Nonsteroidal Anti-Inflammatory Drugs on Vascular Ion Channels:
      Accounting for Cardiovascular Side Effects and Identifying New Therapeutic
      Applications.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used medications for
      the treatment of both acute and chronic pain. Selective cyclooxygenase-2 (COX-2)
      inhibitors, such as celecoxib (Celebrex((r))), rofecoxib (Vioxx((r))), and
      diclofenac, have been among the most widely prescribed NSAIDs because they
      prevent the generation of prostaglandins involved in inflammation and pain, but
      avoid some of the gastrointestinal complications associated with less selective
      COX-1/COX-2 inhibitors. In 2004, rofecoxib (Vioxx((r))) was voluntarily withdrawn
      from the market because of adverse cardiovascular side effects. This led to an
      explosion of research into the cardiovascular effects of the 'coxibs', which
      revealed differential cardiovascular risk profiles among the members of this drug
      class. The differential risk profiles may relate to the tendency of some of the
      drugs to elevate blood pressure (BP). An important component of BP regulation is
      dependent on the contractile state of vascular smooth muscle cells (VSMCs), which
      is controlled to a large extent by the activities of KCNQ (Kv7 family) potassium
      channels and L-type calcium channels. Our recently published data indicate that
      celecoxib, but not rofecoxib or diclofenac, at therapeutically relevant
      concentrations, acts as a Kv7 potassium channel activator and a calcium channel
      blocker, causing relaxation of VSMCs and decreasing vascular tone. These
      vasorelaxant ion channel effects may account for the differential cardiovascular
      risk profiles among the different COX-2 inhibitors. We further speculate that
      these properties may be exploited for therapeutic benefit in the treatment of
      cardiovascular diseases or other medical conditions.

PMID- 20689647
TI  - Fabrication and Characterization of Individually Controlled Multi-Pixel Carbon
      Nanotube Cathode Array Chip for Micro-RT Application for Cancer Research.
AB  - We report here the development of a new carbon nanotube (CNT) field emission
      multi-pixel cathode array chip, a vital component for the multi-pixel beam x-ray
      micro-radiotherapy (micro-RT) system under development in our group for cancer
      research. The CNT field emission cathode array chip has up to 25 (5 * 5)
      individually addressable cathode pixels, each 1 mm in diameter and with center-to
      center distance of 2 mm. The fabrication is a two-step process: first a Cr/Cu
      electrical contact was fabricated on Si substrates with a 5 MUm SiO(2) dielectric
      layer using photolithography; and second the CNTs were selectively deposited on 1
      mm-diameter predefined Cr/Cu contact dots by using a combined
      photolithography/electrophoresis deposition technique. The electron pixel beams
      produced from the multi-pixel array chips are uniform and individually
      controllable. Each pixel beam is expected to generate a dose rate in the order of
      100 cGy/min based on our Monte Carlo simulations.

PMID- 20689648
TI  - Longitudinal functional principal component modeling via Stochastic Approximation
      Monte Carlo.
AB  - The authors consider the analysis of hierarchical longitudinal functional data
      based upon a functional principal components approach. In contrast to standard
      frequentist approaches to selecting the number of principal components, the
      authors do model averaging using a Bayesian formulation. A relatively
      straightforward reversible jump Markov Chain Monte Carlo formulation has poor
      mixing properties and in simulated data often becomes trapped at the wrong number
      of principal components. In order to overcome this, the authors show how to apply
      Stochastic Approximation Monte Carlo (SAMC) to this problem, a method that has
      the potential to explore the entire space and does not become trapped in local
      extrema. The combination of reversible jump methods and SAMC in hierarchical
      longitudinal functional data is simplified by a polar coordinate representation
      of the principal components. The approach is easy to implement and does well in
      simulated data in determining the distribution of the number of principal
      components, and in terms of its frequentist estimation properties. Empirical
      applications are also presented.

PMID- 20689649
TI  - Gold(I)-Catalyzed Hydration of Allenes.
AB  - A gold(I) N-heterocyclic carbene complex catalyzes the intermolecular hydration
      of allenes to form allylic alcohols in modest yield with selective delivery of
      water to the terminal carbon atoms of the allenyl moiety.

PMID- 20689650
TI  - The Relationship of Self-Control and Abstinence Maintenance: An Exploratory
      Analysis of Self-Regulation.
AB  - Studies of self-regulation suggested that self-control requires finite resources
      which, in turn, may present a significant challenge for those trying to recover
      from or control addictive behaviors. The present study examined the relationships
      between self-regulation and abstinence maintenance among adults in recovery (n =
      606: 407 men, 199 women; M age = 38.5 years) residing in self-governed, communal
      living, abstinent homes across the United States. Self-regulation scores
      (controlling for sex and age) were positively related to length of abstinence. In
      addition, a factor analysis of self-regulation scores resulted in some
      differentiation between general self-discipline and impulsivity in self-control
      related to addiction. The relationship between impulsivity and length of
      abstinence was stronger than the relationship derived between general self
      regulation and length of abstinence.

PMID- 20689651
TI  - Messenger RNA expression and methylation of candidate tumor-suppressor genes and
      risk of ovarian cancer-a case-control analysis.
AB  - To investigate the association of expression and promoter methylation of tumor
      suppressor genes with risk of ovarian cancer, we conducted a case-control study
      of 102 patients with serous epithelial ovarian cancer and 100 patients without
      ovarian cancers. We measured mRNA expression levels (by real-time reverse
      transcription polymerase chain reaction) and methylation status (by methylation
      specific polymerase chain reaction) of five candidate genes (BRCA1, BRCA2, hMLH1,
      MGMT, and DNMT3B) in tumors from the cases and normal ovaries from the controls.
      We found that mRNA expression levels of the five genes were decreased in tumors
      than in normal ovaries with 0.39-fold for BRCA1, 0.25-fold for BRCA2, 0.42-fold
      for hMLH1, 0.45-fold for MGMT, and 0.87-fold for DNMT3B, calculated by the 2(
      DeltaDeltaCT) method. Ovarian cancer risk (odds ratios, ORs) was associated with
      low expression of all genes (2.95 [95% confidence interval (CI), 1.51 - 5.78] for
      BRCA1, 3.65 (95% CI, 1.82 - 7.30) for BRCA2, 5.25 (95% CI, 2.52 - 10.96) for
      hMLH1, and 4.72 (95% CI, 2.32 - 9.62) for MGMT) but not DNMT3B. However,
      methylation status was not associated with gene expression levels in the tumors,
      except for hMLH1 whose mean (+/- SD) gene expression was significantly lower in
      methylated (13.0 +/- 7.6) than in unmethylated (31.2 +/- 44.8) tumors (P <
      0.001). We concluded that low mRNA expression of these tumor-suppressor genes,
      likely due to molecular mechanisms in addition to the promoter methylation in
      some instances, may be a biomarker for ovarian cancer risk in this study
      population. Larger studies are needed to validate our findings.

PMID- 20689652
TI  - Mining Approximate Order Preserving Clusters in the Presence of Noise.
AB  - Subspace clustering has attracted great attention due to its capability of
      finding salient patterns in high dimensional data. Order preserving subspace
      clusters have been proven to be important in high throughput gene expression
      analysis, since functionally related genes are often co-expressed under a set of
      experimental conditions. Such co-expression patterns can be represented by
      consistent orderings of attributes. Existing order preserving cluster models
      require all objects in a cluster have identical attribute order without
      deviation. However, real data are noisy due to measurement technology limitation
      and experimental variability which prohibits these strict models from revealing
      true clusters corrupted by noise. In this paper, we study the problem of
      revealing the order preserving clusters in the presence of noise. We propose a
      noise-tolerant model called approximate order preserving cluster (AOPC). Instead
      of requiring all objects in a cluster have identical attribute order, we require
      that (1) at least a certain fraction of the objects have identical attribute
      order; (2) other objects in the cluster may deviate from the consensus order by
      up to a certain fraction of attributes. We also propose an algorithm to mine
      AOPC. Experiments on gene expression data demonstrate the efficiency and
      effectiveness of our algorithm.

PMID- 20689653
TI  - Hope and Substance Abuse Recovery: The Impact of Agency and Pathways within an
      Abstinent Communal-living Setting.
AB  - Hope is commonly divided into two constructs: agency, defined as goal-directed
      energy, and pathways, defined as the ability to create paths to a goal. To date,
      only two studies have examined the utility of hope in substance abuse recovery,
      and the present investigation buildings on this small literature by assessing
      hope beliefs within a larger and more diverse sample of adults in recovery. This
      study examined how two hope constructs of agency and pathways related to
      substance use abstinence among 90 new residents of communal-living recovery homes
      (i.e., Oxford Houses) who completed two waves of data assessment. Results
      indicated that agency scores significantly predicted alcohol use at Wave 1 but
      pathway scores failed to predict drug or alcohol use at this time point.
      Additionally, agency and pathway scores predicted drug (but not alcohol use) at
      an 8-month follow-up assessment. These findings indicated that participants' hope
      may be linked to substance use at later stages of recovery. In addition, these
      results suggested a stronger relationship between hope and drug as opposed to
      alcohol use at this time point. Implications for substance abuse recovery are
      discussed.

PMID- 20689654
TI  - Application of the Actor-Critic Architecture to Functional Electrical Stimulation
      Control of a Human Arm.
AB  - Clinical tests have shown that the dynamics of a human arm, controlled using
      Functional Electrical Stimulation (FES), can vary significantly between and
      during trials. In this paper, we study the application of the actor-critic
      architecture, with neural networks for the both the actor and the critic, as a
      controller that can adapt to these changing dynamics of a human arm. Development
      and tests were done in simulation using a planar arm model and Hill-based muscle
      dynamics. We begin by training it using a Proportional Derivative (PD) controller
      as a supervisor. We then make clinically relevant changes to the dynamics of the
      arm and test the actor-critic's ability to adapt without supervision in a
      reasonable number of episodes. Finally, we devise methods for achieving both
      rapid learning and long-term stability.

PMID- 20689655
TI  - The Physiome Projects and Multiscale Modeling.

PMID- 20689656
TI  - A SPECTRAL GRAPH APPROACH TO DISCOVERING GENETIC ANCESTRY.
AB  - Mapping human genetic variation is fundamentally interesting in fields such as
      anthropology and forensic inference. At the same time, patterns of genetic
      diversity confound efforts to determine the genetic basis of complex disease. Due
      to technological advances, it is now possible to measure hundreds of thousands of
      genetic variants per individual across the genome. Principal component analysis
      (PCA) is routinely used to summarize the genetic similarity between subjects. The
      eigenvectors are interpreted as dimensions of ancestry. We build on this idea
      using a spectral graph approach. In the process we draw on connections between
      multidimensional scaling and spectral kernel methods. Our approach, based on a
      spectral embedding derived from the normalized Laplacian of a graph, can produce
      more meaningful delineation of ancestry than by using PCA. The method is stable
      to outliers and can more easily incorporate different similarity measures of
      genetic data than PCA. We illustrate a new algorithm for genetic clustering and
      association analysis on a large, genetically heterogeneous sample.

PMID- 20689657
TI  - ?
AB  - This study evaluates up to which degree physicians of Hospital Dr. Dario
      Contreras of Dominican Republic know, respect, inform and apply the General
      Health Law in relation to the right of Jehovah witness patients to refuse being
      blood transfused (respect to their autonomy). It also evaluates whether Jehovah
      witnesses know General Health Law and in which degree they have been benefited by
      putting it into practice. The study reveals that Jehovah Witnesses do not know
      the law.

PMID- 20689658
TI  - The Relationship of Gender and Ethnicity to Employment Among Adults Residing in
      Communal-living Recovery Homes.
AB  - This study examined employment and sources of income for different genders and
      ethnic groups residing in a substance abuse recovery homes called Oxford Houses.
      Men compared to women reported significantly higher mean income from employment
      as well as total income. African Americans compared to European Americans
      reported significantly more work in the past 30 days; however, the rate of pay
      between these two ethnic groups was not significantly different. Longer length of
      stay in Oxford House was related to higher incomes. Implications of these
      findings are discussed.

PMID- 20689659
TI  - Molecular and Microstructural Imaging of the Myocardium.
AB  - The past year has witnessed ongoing progress in the field of molecular MRI of the
      myocardium. In addition, several novel fluorescent agents have been introduced
      and used to image remodeling in the injured myocardium. New techniques to image
      myocardial microstructure, such as diffusion spectrum MRI, have also been
      introduced and have tremendous potential for integration and synergy with
      molecular MRI. In the current review we focus on these and other advances in the
      field that have occurred over the past year.

PMID- 20689660
TI  - Measuring In-Group and Out-Group Helping in Communal Living: Helping and
      Substance Abuse Recovery.
AB  - With a national U.S. sample of communal-living residents in substance abuse
      recovery, the tendency to help members inside and/or outside their community was
      examined. Study 1 (n = 670) developed of the Communal Living In-Group Helping
      Scale to distinguish helping directed toward housemates vs. others. Study 2 (n =
      419) used this communal helping measure and a general altruism scale to explore
      gender, ethnicity, and 12-Step sponsorship related to in-group (housemates) and
      out-group (others in the community) behaviors. Results revealed significant sex
      differences and significantly higher helping for both men and women was reported
      among 12-Step sponsors along two dimensions. Implications focused on gender
      related differences in social helping interactions and in-group formation in
      recovery communities.

PMID- 20689661
TI  - Oxford House and Alcoholics Anonymous: The Impact of Two Mutual-help Models on
      Abstinence.
AB  - Two examples of mutual-help approaches for substance abuse recovery are 12-step
      groups (AA and NA) and Oxford House. The present study examined the combined
      effects of AA and Oxford House residence on abstinence over a 24-month period
      with 150 individuals randomly assigned to either an Oxford House or to usual
      after-care. Among individuals with high 12-step involvement, the addition of
      Oxford House residence significantly increased the odds of abstinence (87.5% vs.
      52.9%). However, among participants with low 12-step involvement, rates of
      abstinence were fairly similar across conditions (31.4% vs. 21.2%). Results
      suggested that the joint effectiveness of these mutual-help programs may promote
      abstinence.

PMID- 20689662
TI  - On the application of (topographic) independent and tree-dependent component
      analysis for the examination of DCE-MRI data.
AB  - In this contribution we investigate the applicability of different methods from
      the field of independent component analysis (ICA) for the examination of dynamic
      contrast-enhanced magnetic resonance imaging (DCE-MRI) data from breast cancer
      research. DCE-MRI has evolved in recent years as a powerful complement to X-ray
      based mammography for breast cancer diagnosis and monitoring. In DCE-MRI the time
      related development of the signal intensity after the administration of a
      contrast agent can provide valuable information about tissue states and
      characteristics. To this end, techniques related to ICA, offer promising options
      for data integration and feature extraction at voxel level. In order to evaluate
      the applicability of ICA, topographic ICA and tree-dependent component analysis
      (TCA), these methods are applied to twelve clinical cases from breast cancer
      research with a histopathologically confirmed diagnosis. For ICA these
      experiments are complemented by a reliability analysis of the estimated
      components. The outcome of all algorithms is quantitatively evaluated by means of
      receiver operating characteristics (ROC) statistics whereas the results for
      specific data sets are discussed exemplarily in terms of reification, score-plots
      and score images.

PMID- 20689663
TI  - Bias Mechanisms in Intention-to-Treat Analysis With Data Subject to Treatment
      Noncompliance and Missing Outcomes.
AB  - An analytical approach was employed to compare sensitivity of causal effect
      estimates with different assumptions on treatment noncompliance and non-response
      behaviors. The core of this approach is to fully clarify bias mechanisms of
      considered models and to connect these models based on common parameters.
      Focusing on intention-to-treat analysis, systematic model comparisons are
      performed on the basis of explicit bias mechanisms and connectivity between
      models. The method is applied to the Johns Hopkins school intervention trial,
      where assessment of the intention-to-treat effect on school children's mental
      health is likely to be affected by assumptions about intervention noncompliance
      and nonresponse at follow-up assessments. The example calls attention to the
      importance of focusing on each case in investigating relative sensitivity of
      causal effect estimates with different identifying assumptions, instead of
      pursuing a general conclusion that applies to every occasion.

PMID- 20689664
TI  - Geographic object-based delineation of neighborhoods of Accra, Ghana using
      QuickBird satellite imagery.
AB  - The objective was to test GEographic Object-based Image Analysis (GEOBIA)
      techniques for delineating neighborhoods of Accra, Ghana using QuickBird
      multispectral imagery. Two approaches to aggregating census enumeration areas
      (EAs) based on image-derived measures of vegetation objects were tested: (1)
      merging adjacent EAs according to vegetation measures and (2) image segmentation.
      Both approaches exploit readily available functions within commercial GEOBIA
      software. Image-derived neighborhood maps were compared to a reference map
      derived by spatial clustering of slum index values (from census data), to provide
      a relative assessment of potential map utility. A size-constrained iterative
      segmentation approach to aggregation was more successful than standard image
      segmentation or feature merge techniques. The segmentation approaches account for
      size and shape characteristics, enabling more realistic neighborhood boundaries
      to be delineated. The percentage of vegetation patches within each EA yielded
      more realistic delineation of potential neighborhoods than mean vegetation patch
      size per EA.

PMID- 20689665
TI  - Presence of Batrachochytrium dendrobatidis at the Headwaters of the Mississippi
      River, Itasca State Park, Minnesota, USA.

PMID- 20689666
TI  - Comparing Object Alignment Algorithms with Appearance Variation: Forward-Additive
      vs Inverse-Composition.
AB  - A common problem that affects object alignment algorithms is when they have to
      deal with objects with unseen intra-class appearance variation. Several variants
      based on gradient-decent algorithms, such as the Lucas-Kanade (or forward
      additive) and inverse-compositional algorithms, have been proposed to deal with
      this issue by solving for both alignment and appearance simultaneously. In [1],
      Baker and Matthews showed that without appearance variation, the inverse
      compositional (IC) algorithm was theoretically and empirically equivalent to the
      forward-additive (FA) algorithm, whilst achieving significant improvement in
      computational efficiency. With appearance variation, it would be intuitive that a
      similar benefit of the IC algorithm would be experienced over the FA counterpart.
      However, to date no such comparison has been performed. In this paper we remedy
      this situation by performing such a comparison. In this comparison we show that
      the two algorithms are not equivalent due to the inclusion of the appearance
      variation parameters. Through a number of experiments on the MultiPIE face
      database, we show that we can gain greater refinement using the FA algorithm due
      to it being a truer solution than the IC approach.

PMID- 20689667
TI  - REDUS: Finding Reducible Subspaces in High Dimensional Data.
AB  - Finding latent patterns in high dimensional data is an important research problem
      with numerous applications. The most well known approaches for high dimensional
      data analysis are feature selection and dimensionality reduction. Being widely
      used in many applications, these methods aim to capture global patterns and are
      typically performed in the full feature space. In many emerging applications,
      however, scientists are interested in the local latent patterns held by feature
      subspaces, which may be invisible via any global transformation.In this paper, we
      investigate the problem of finding strong linear and nonlinear correlations
      hidden in feature subspaces of high dimensional data. We formalize this problem
      as identifying reducible subspaces in the full dimensional space. Intuitively, a
      reducible subspace is a feature subspace whose intrinsic dimensionality is
      smaller than the number of features. We present an effective algorithm, REDUS,
      for finding the reducible subspaces. Two key components of our algorithm are
      finding the overall reducible subspace, and uncovering the individual reducible
      subspaces from the overall reducible subspace. A broad experimental evaluation
      demonstrates the effectiveness of our algorithm.

PMID- 20689668
TI  - Differential effects of prolonged work on performance measures in self-paced
      speed tests.
AB  - Time-related changes in the speeded performance of complex cognitive tasks are
      considered to arise from the combined effects of practice and mental fatigue.
      Here we explored the differential contributions of practice and fatigue to
      performance changes in a self-paced speeded mental addition and comparison task
      of about 50 min duration, administered twice within one week's time. Performance
      measures included average response speed, accuracy, and response speed
      variability. The results revealed differential effects of prolonged work on
      different performance indices: Practice effects, being more pronounced in the
      first session, were reflected in an improvement of average response speed,
      whereas mental fatigue, occurring in both sessions, was reflected in an increase
      of response speed variability. This demonstrates that effects of mental fatigue
      on average speed of performance may be masked by practice effects but still be
      detectable in the variability of performance. Therefore, besides experimental
      factors such as the length and complexity of tasks, indices of response speed
      variability should be taken into consideration when interpreting different
      aspects of performance in self-paced speed tests.

PMID- 20689669
TI  - A filled duration illusion in music: Effects of metrical subdivision on the
      perception and production of beat tempo.
AB  - This study replicates and extends previous findings suggesting that metrical
      subdivision slows the perceived beat tempo (Repp, 2008). Here, musically trained
      participants produced the subdivisions themselves and were found to speed up,
      thus compensating for the perceived slowing. This was shown in a synchronization
      continuation paradigm (Experiment 1) and in a reproduction task (Experiment 2a).
      Participants also judged the tempo of a subdivided sequence as being slower than
      that of a preceding simple beat sequence (Experiment 2b). Experiment 2 also
      included nonmusician participants, with similar results. Tempo measurements of
      famous pianists' recordings of two variation movements from Beethoven sonatas
      revealed a strong tendency to play the first variation (subdivided beats) faster
      than the theme (mostly simple beats). A similar tendency was found in musicians'
      laboratory performances of a simple theme and variations, despite instruc-tions
      to keep the tempo constant (Experiment 3a). When playing melodic sequences in
      which only one of three beats per measure was subdivided, musicians tended to
      play these beats faster and to perceive them as longer than adjacent beats, and
      they played the whole sequence faster than a sequence without any subdivisions
      (Experiments 3b and 3c). The results amply demonstrate a filled duration illusion
      in rhythm perception and music performance: Intervals containing events seem
      longer than empty intervals and thus must be shortened to be perceived as equal
      in duration.

PMID- 20689670
TI  - Biocatalytic asymmetric formation of tetrahydro-beta-carbolines.
AB  - Strictosidine synthase triggers the formation of strictosidine from tryptamine
      and secologanin, thereby generating a carbon-carbon bond and a new stereogenic
      center. Strictosidine contains a tetrahydro-beta-carboline moiety - an important
      N-heterocyclic framework found in a range of natural products and synthetic
      pharmaceuticals. Stereoselective methods to produce tetrahydro-beta-carboline
      enantiomers are greatly valued. We report that strictosidine synthase from
      Ophiorrhiza pumila utilizes a range of simple achiral aldehydes and substituted
      tryptamines to form highly enantioenriched (ee >98%) tetrahydro-beta-carbolines
      via a Pictet-Spengler reaction. This is the first example of aldehyde substrate
      promiscuity in the strictosidine synthase family of enzymes and represents a
      first step towards developing a general biocatalytic strategy to access chiral
      tetrahydro-beta-carbolines.

PMID- 20689671
TI  - Indigenous Native American Healing Traditions.

PMID- 20689672
TI  - From Fifth Business to Protagonist: the complex roles of ion channel anchors in
      cardiac arrhythmia.
AB  - Proper regulation of cardiac ion channel activity is critical for cellular ion
      homeostasis and myocyte electrical activity. Recent work has demonstrated that
      cardiac ion channels are not isolated pores in plasmid membranes, but rather
      exist within macromolecular signaling complexes. Moreover, within these macro
      complexes resides the machinery to finely tune ion channel expression, activity,
      and signaling. While it is widely-accepted that mutations in ion channel pore
      forming genes underlie a number of cardiac arrhythmias, current research is now
      focusing on the roles of auxiliary subunits in the development of arrhythmia
      syndromes.

PMID- 20689673
TI  - Microwave-assisted Organic Synthesis of a High-affinity Pyrazolo-pyrimidinyl TSPO
      Ligand.
AB  - We herein report a dramatically improved total synthesis of the high-affinity
      translocator protein (TSPO) ligand DPA-714, featuring microwave-assisted organic
      synthesis (MAOS). Compared with previously described approaches, our novel MAOS
      method dramatically reduces overall reaction time without adversely effecting
      reaction yields. We envision that the described MAOS protocol may be suitably
      applied to high-throughput, diversity-oriented synthesis of novel compounds based
      on the pyrazolo-pyrimidinyl scaffold. Such an approach could accelerate the
      development of focused libraries of novel TSPO ligands with potential for future
      development as molecular imaging and therapeutic agents.

PMID- 20689674
TI  - FDG PET in the Evaluation of Parkinson's Disease.
AB  - Network analysis of (18)F-fluorodeoxyglucose (FDG) positron emission tomography
      (PET) is an innovative approach for the study of in movement disorders, such as
      Parkinson's disease (PD). Spatial covariance analysis of imaging data acquired
      from PD patients has revealed characteristic regional patterns associated with
      the motor and cognitive features of disease. Quantification of pattern expression
      in individual patients can be used for diagnosis, assessment of disease severity,
      and evaluation of novel medical and surgical therapies. Identification of disease
      specific patterns in other parkinsonian syndromes, such as multiple system
      atrophy and progressive supranuclear palsy, has improved diagnostic accuracy in
      patients with difficult to diagnose parkinsonism. Further developments of these
      techniques are likely to enhance the role of functional imaging in investigating
      underlying abnormalities and potential new therapies in these neurodegenerative
      diseases.

PMID- 20689675
TI  - Meeting the Basic Needs of Children: Does Income Matter?
AB  - We review existing research and policy evidence about income as an essential
      component to meeting children's basic needs-that is, income represented as the
      purest monetary transfer for increasing the purchasing power of low income
      families. Social scientists have made great methodological strides in
      establishing whether income has independent effects on the cognitive development
      of low-income children. Our review of that research suggests that a $1,000
      increase in income has positive, but small, effects on children, rarely exceeding
      1/10(th) of a standard deviation change in outcomes for children. We argue that
      researchers are well-positioned for more rigorous investigations about how and
      why income affects children, but only first with thoughtful and creative regard
      for conceptual clarity, and on understanding income's potentially inter-related
      influences on socio-emotional development, mental, and physical health. We also
      argue for more focus on the effects of income transfers, including when
      conditional on employment, as compared to more targeted direct investments in
      children. We end with a description of two-generation and cafeteria-style
      programs as the frontiers of the next generation in income-enhancement policies,
      and with the promise of insights from behavioral economics.

PMID- 20689676
TI  - A Long Time Coming - The Creation of an Evidence Base for Physical Activity
      Prescription to Improve Health Outcomes in Bipolar Disorder.

PMID- 20689677
TI  - How Adolescent Girls Understand and Manage Depression Within Their Peer Group: A
      Grounded Theory Investigation.
AB  - Depression is prevalent among adolescent girls, but few receive mental health
      treatment. Adolescent girls often forgo needed mental health treatment because
      they fear responses of peers about depression. Understanding the processes of how
      adolescent girls respond to peers with depression is an important first step to
      improve access to mental health treatment. This qualitative study describes the
      knowledge, perceptions, and behaviors of adolescent girls about depression and
      mental health treatment within their peer group. The investigators conducted two
      focus groups, with adolescent girls (n=21), in a public high school in the
      southern U.S. Grounded theory methods were utilized to identify a beginning
      substantive theory about perceptions and behaviors of adolescent girls related to
      depression in their peers. Participants cognitively processed mental health
      concepts similarly to adults. However, their affective responses to peers with
      mental illness fluctuated between adult and child perspectives. Participants
      expressed concerns about individuals with depression that have previously been
      identified in adults, but expressed unique perspectives that reflect their
      transitional stage of development. Findings provide new information about how
      adolescent girls respond to peers with depression, define areas for further
      investigation, provide directions for constructing developmentally appropriate
      mental health educational interventions for adolescent girls, and elucidate the
      need to provide guidance to women with whom adolescent girls have sustained
      contact.

PMID- 20689678
TI  - Scaling of transverse nuclear magnetic relaxation due to magnetic nanoparticle
      aggregation.
AB  - The aggregation of superparamagnetic iron oxide (SPIO) nanoparticles decreases
      the transverse nuclear magnetic resonance (NMR) relaxation time T2CP of adjacent
      water molecules measured by a Carr-Purcell-Meiboom-Gill (CPMG) pulse-echo
      sequence. This effect is commonly used to measure the concentrations of a variety
      of small molecules. We perform extensive Monte Carlo simulations of water
      diffusing around SPIO nanoparticle aggregates to determine the relationship
      between T2CP and details of the aggregate. We find that in the motional averaging
      regime T2CP scales as a power law with the number N of nanoparticles in an
      aggregate. The specific scaling is dependent on the fractal dimension d of the
      aggregates. We find T2CP?N-0.44 for aggregates with d = 2.2, a value typical of
      diffusion limited aggregation. We also find that in two-nanoparticle systems,
      T2CP is strongly dependent on the orientation of the two nanoparticles relative
      to the external magnetic field, which implies that it may be possible to sense
      the orientation of a two-nanoparticle aggregate. To optimize the sensitivity of
      SPIO nanoparticle sensors, we propose that it is best to have aggregates with few
      nanoparticles, close together, measured with long pulse-echo times.

PMID- 20689680
TI  - The Sociology of Discrimination: Racial Discrimination in Employment, Housing,
      Credit, and Consumer Markets.
AB  - Persistent racial inequality in employment, housing, and a wide range of other
      social domains has renewed interest in the possible role of discrimination. And
      yet, unlike in the pre-civil rights era, when racial prejudice and discrimination
      were overt and widespread, today discrimination is less readily identifiable,
      posing problems for social scientific conceptualization and measurement. This
      article reviews the relevant literature on discrimination, with an emphasis on
      racial discrimination in employment, housing, credit markets, and consumer
      interactions. We begin by defining discrimination and discussing relevant methods
      of measurement. We then provide an overview of major findings from studies of
      discrimination in each of the four domains; and, finally, we turn to a discussion
      of the individual, organizational, and structural mechanisms that may underlie
      contemporary forms of discrimination. This discussion seeks to orient readers to
      some of the key debates in the study of discrimination and to provide a roadmap
      for those interested in building upon this long and important line of research.

PMID- 20689681
TI  - RNA structural motifs that entail hydrogen bonds involving sugar-phosphate
      backbone atoms of RNA.
AB  - The growing number of high-resolution crystal structures of large RNA molecules
      provides much information for understanding the principles of structural
      organization of these complex molecules. Several in-depth analyses of nucleobase
      centered RNA structural motifs and backbone conformations have been published
      based on this information, including a systematic classification of base pairs by
      Leontis and Westhof. However, hydrogen bonds involving sugar-phosphate backbone
      atoms of RNA have not been analyzed systematically until recently, although such
      hydrogen bonds appear to be common both in local and tertiary interactions. Here
      we review some backbone structural motifs discussed in the literature and analyze
      a set of eight high-resolution multi-domain RNA structures. The analyzed RNAs are
      highly structured: among 5372 nucleotides in this set, 89% are involved in at
      least one "long-range" RNA-RNA hydrogen bond, i.e., hydrogen bonds between atoms
      in the same residue or sequential residues are ignored. These long-range hydrogen
      bonds frequently use backbone atoms as hydrogen bond acceptors, i.e., OP1, OP2,
      O2', O3', O4', or O5', or as a donor (2'OH). A surprisingly large number of such
      hydrogen bonds are found, considering that neither single-stranded nor double
      stranded regions will contain such hydrogen bonds unless additional interactions
      with other residues exist. Among 8327 long-range hydrogen bonds found in this set
      of structures, 2811, or about one-third, are hydrogen bonds entailing RNA
      backbone atoms; they involve 39% of all nucleotides in the structures. The
      majority of them (2111) are hydrogen bonds entailing ribose hydroxyl groups,
      which can be used either as a donor or an acceptor; they constitute 25% of all
      hydrogen bonds and involve 31% of all nucleotides. The phosphate oxygens OP1 or
      OP2 are used as hydrogen bond acceptors in 12% of all nucleotides, and the ribose
      ring oxygen O4' and phosphodiester oxygens O3' and O5' are used in 4%, 4%, and 1%
      of all nucleotides, respectively. Distributions of geometric parameters and some
      examples of such hydrogen bonds are presented in this report. A novel motif
      involving backbone hydrogen bonds, the ribose-phosphate zipper, is also
      identified.

PMID- 20689682
TI  - Broadband Heteronuclear Solid-State NMR Experiments by Exponentially Modulated
      Dipolar Recoupling without Decoupling.
AB  - We present a novel solid-state NMR method for heteronuclear dipolar recoupling
      without decoupling. The method, which introduces the concept of exponentially
      modulated rf fields, provides efficient broadband recoupling with large
      flexibility with respect to hetero- or homonuclear applications, sample spinning
      frequency, and operation without the need for high-power (1)H decoupling. For
      previous methods, the latter has been a severe source of sample heating which may
      cause detoriation of costly samples. The so-called EXPonentially mOdulated
      Recoupling Technique (EXPORT) is described analytically and numerically, and
      demonstrated experimentally by 1D (13)C spectra and 2D (13)C-(15)N correlation
      spectra of (13)C,(15)N-labeled samples of GB1, ubiquitin, and fibrils of the
      SNNFGAILSS fragment of amylin. Through its flexible operation, robustness, and
      strong performance, it is anticipated that EXPORT will find immediate application
      for both hetero- and homonuclear dipolar recoupling in solid-state NMR of
      (13)C,(15)N-labeled proteins and compounds of relevance in chemistry.

PMID- 20689683
TI  - NEIGHBORHOOD CONTEXT AND THE DEVELOPMENT OF AGGRESSION IN BOYS AND GIRLS.
AB  - We examine the roles of neighborhood characteristics in the development of the
      aggressive behavior of 1,409 urban boys and girls between the first and seventh
      grades. The multilevel, longitudinal growth analyses find strong neighborhood
      effects in all models, while controlling for individual-level variables. Results
      indicated that the effects of neighborhood violence, employment, income, and
      percentages of single males and female-headed households do not manifest in first
      grade, but affect the trajectory of child aggression between first and seventh
      grades. The influence of family income and frequent physical discipline on boys'
      and girls' aggression occurs at first grade, and family income has a modest
      effect on the trajectory. The findings strongly suggest that the neighborhood
      sources of the development of child aggression are independent and different from
      early childhood experiences.

PMID- 20689684
TI  - A Simple Test Tube-Based ELISA Experiment for the High-School Classroom.
AB  - Immunology is gaining prominence both in the media as well as on the Advanced
      Placement (AP) exam in Biology. One of the challenges of teaching modern
      biological topics such as immunology and biochemistry in the high-school setting
      is the increased reliance on expensive technology in the research world. To begin
      to bridge this widening gap, we devised an experiment using a novel macroscale
      enzyme-linked immunosorbent assay that is suitable for AP-level high-school
      biology classrooms as well as entry-level collegiate laboratories. This novel
      method does not require a plate reader for data analysis, but instead relies on
      more common and inexpensive equipment such as a clinical test tube centrifuge and
      a simple test tube spectrophotometer. The experimental plan focuses on students
      measuring antibody concentrations in "unknown" samples and includes the
      collection and analysis of a standard curve using reagents prepared by the
      instructor. Students will be introduced to enzyme action, quantitative laboratory
      technique, antibodies, and the immune system, with the overall goal being to
      explore and highlight the inherent connections within the fields of biochemistry
      and immunology.

PMID- 20689685
TI  - Discrimination in a Low-Wage Labor Market: A Field Experiment.
AB  - Decades of racial progress have led some researchers and policymakers to doubt
      that discrimination remains an important cause of economic inequality. To study
      contemporary discrimination, we conducted a field experiment in the low-wage
      labor market of New York City, recruiting white, black, and Latino job applicants
      who were matched on demographic characteristics and interpersonal skills. These
      applicants were given equivalent resumes and sent to apply in tandem for hundreds
      of entry-level jobs. Our results show that black applicants were half as likely
      as equally qualified whites to receive a callback or job offer. In fact, black
      and Latino applicants with clean backgrounds fared no better than white
      applicants just released from prison. Additional qualitative evidence from our
      applicants' experiences further illustrates the multiple points at which
      employment trajectories can be deflected by various forms of racial bias. These
      results point to the subtle yet systematic forms of discrimination that continue
      to shape employment opportunities for low-wage workers.

PMID- 20689686
TI  - Safe spinal anesthesia in a woman with chronic renal failure and placenta previa.
AB  - BACKGROUND: Chronic renal failure is strongly associated with poor pregnancy
      outcome. Women dependent on hemodialysis before conception rarely achieve a
      successful live birth. CASE PRESENTATION: A 31-year-old multiparous Turkish woman
      was scheduled for cesarean section under spinal anesthesia at 37 weeks and five
      days' gestation because of hemorrhage due to secondary placenta previa. Spinal
      anesthesia with 8 mg of hyperbaric bupivacaine was successfully performed.
      Invasive blood pressure, central venous pressure, and heart rate were stable
      during the surgery. The mother returned to regular hemodialysis on the first
      postoperative day. CONCLUSION: Pregnancy is uncommon in women with chronic renal
      failure requiring chronic dialysis. Rates of maternal hypertension, pre
      eclampsia, anemia, and infection in the pregnant chronic dialysis patient are
      high. However, our findings suggest that with careful, close, and effective
      monitoring preoperatively and intraoperatively, spinal anesthesia can be safely
      performed for cesarean section in patients undergoing hemodialysis.

PMID- 20689687
TI  - Amoxicillin-induced aseptic meningoencephalitis.
AB  - Meningitis is usually produced by an infectious agent, but there are multiple
      noninfectious causes. Drug-induced aseptic meningitis (DIAM) is an important
      entity and has been reported as an uncommon adverse reaction with numerous
      agents. Thus, DIAM constitutes a diagnostic and patient management challenge. We
      present a patient with three episodes of aseptic meningitis due to amoxicillin,
      and then review the literature on this rare idiosyncratic event which may occur
      after local or systemic drug administration. A 77-year-old man was admitted to
      our hospital with fever, headache, and neck stiffness. Seven days before
      admission he had a dental and gingival inflammation. He was treated with two oral
      doses of 500 mg daily of amoxicillin for one week. The seventh day he awoke with
      the complaints that prompted hospital admittance. Amoxicillin was stopped 1 day
      before his admission. From his history we knew of two similar episodes: The first
      episode was after a dental procedure 3 months before this incident. He had
      received a 1-week course of postprocedure amoxicillin of 500 mg daily and had
      similar headache, fever, and chills during the entire course of treatment. He
      wasn't admitted to the hospital, because he stopped taking amoxicillin and he
      felt spontaneous pain relief after taking symptomatic pain treatment. The second
      episodes was 6 months after his first admission, he had been admitted to our
      hospital with the same symptoms. Amoxicillin was stopped and changed with
      intravenous (IV) ceftriaxone (CTRX) for 10 days due to suspected partial
      untreated meningitis. The patient improved rapidly within 2 days and was
      discharged from the hospital. On the basis of these three confirmed episodes of
      meningitis after recurrent exposure to amoxicillin, with repetitive negative
      testing for viral, bacterial, and mycobacterial micro-organisms, we diagnosed
      aseptic meningitis induced by amoxicillin. To our knowledge, this is the seventh
      well documented publication of such a severe side effect of a commonly used
      antibiotic.

PMID- 20689688
TI  - "Later, lazier, and unluckier": a heuristic profile of high vulnerability is an
      independent predictor of uncontrolled blood pressure (the PREVIEW study).
AB  - OBJECTIVE: Vulnerability profiling, an alternative to deterministic risk
      assessment, offers clinicians a more intuitive but empirically-grounded
      assessment of patient risk. This study aimed to determine whether a heuristic
      profile of high vulnerability is an independent predictor of uncontrolled
      hypertension. METHODS: Secondary analysis of prospective observational study data
      on 2999 hypertensive patients treated with valsartan. Predictive validity of
      vulnerability profiling for first-line, second-line, and first-or-second-line
      antihypertensive treatment was inferred from 1) logistic regression models with
      adequate statistical fit, 2) statistically significant odds ratios for
      uncontrolled BP for the high-vulnerability cluster exceeding 1.00, and 3) correct
      classification rates for patients' BP control status. RESULTS: All models of
      uncontrolled BP were significant (P < 0.001); all odds ratios for the high
      vulnerability cluster were greater than 1.00 and significant (P < 0.001). Correct
      classification rates for the highly-vulnerability cluster on uncontrolled BP
      after first-line, second-line, or either treatment were 91.1%, 61.2%, and 93.5%
      for systolic BP; 74.5%, 65.8%, and 76.7% for diastolic BP; and 92.8%, 65.3%, and
      94.6% for combined systolic and diastolic BP. CONCLUSION: The heuristic profile
      of "later, lazier, and unluckier" is an intuitive and valid tool to help identify
      patients at greater risk for poor BP control seen in general practice.

PMID- 20689689
TI  - Management of osteoporotic vertebral fractures.
AB  - Osteoporotic vertebral fractures are associated with considerable reduction of
      quality of life, morbidity, and mortality. The management of patients with
      vertebral fractures should include treatment for osteoporosis and measures to
      reduce pain and improve mobility. This article provides information for
      management and rehabilitation of vertebral fractures based on clinical experience
      and literature.

PMID- 20689690
TI  - Burden of diabetes in the adult Chinese population: A systematic literature
      review and future projections.
AB  - BACKGROUND: The diabetes epidemic in China imposes an increasing burden on the
      health care system and the economy. We derived prospective diabetes prevalence
      rates in China until 2016 from a systematic review of the published literature in
      the period 1987-2007. The results could help to guide resources of the Chinese
      health care system in order to address the diabetes epidemic. METHODS: We
      selected articles published in the English/Chinese languages from MEDLINE and the
      China Wanfang Digital Database using the keywords "China", "diabetes mellitus",
      "prevalence", and "epidemiology" in order to estimate the current diabetes
      prevalence in China. For projecting future prevalence rates, we considered the
      population growth, and assumed that China's diabetes prevalence in first tier
      cities in 2016 would equal Hong Kong's diabetes prevalence in 2007. RESULTS: The
      number of Chinese adults with diabetes is projected to rise from 53.1 million in
      2009 to 76.1 million in 2016. The estimated diabetes prevalence rate in China in
      2009 was 3.9% (urban 5.2%, rural 2.9%) and is projected to increase to 5.4%
      (urban 6.9%, rural 3.8%) in 2016, corresponding to an annual consolidated
      aggregate growth rate of 4.6%. CONCLUSION: We estimate a considerably higher
      diabetes prevalence in the adult Chinese population than that reported in
      previous studies. The diabetes prevalence will continue to rise in the future,
      which points to the importance of increasing awareness and better diagnosis of
      diabetes in China.

PMID- 20689691
TI  - Olfactory dysfunction in Parkinson's disease: Benefits of quantitative odorant
      examination.
AB  - Olfactory involvement is well recognized in patients with Parkinson's disease
      (PD). The purpose of this study was to examine smell function quantitatively,
      using different types and concentrations of odorants in PD patients. We aimed to
      elucidate whether a specific odor can affect the severity and duration of PD
      patients. A total of 89 nondemented PD patients and 20 age-matched controls
      participated in the study. Quantitative evaluation of smell function was
      performed using the T and T olfactometer test. This test contains five kinds of
      odorants at different concentrations. Recognition threshold (RT) scores for all
      five odorants and for each individual odorant were measured in five groups of PD
      patients with Hoehn and Yale (HY) stages I (n = 12), II (n = 24), III (n = 43),
      and IV (n = 10), as well as in control subjects (n = 20). One-way analysis of
      variance and Ryan's method were used for statistical comparison between the five
      groups. Compared with controls and HY I patients, total RT scores were
      significantly higher in HY II, III, and IV patients. There were no statistically
      significant differences in RT scores between HY I patients and controls. However,
      total RT scores for three HY I patients (25%) were higher than the mean + two
      standard deviations of controls. On single odorant testing, significant higher RT
      scores for methylcyclopentenolone and skatol were found in HY II, III, and IV
      patients, in comparison with controls and HY I patients. The remaining three
      odorants did not differ statistically between PD patients and control subjects.
      The present study indicated that hyposmia in PD patients increased from HY II
      onwards. A single odorant of methyl cyclopentenolone or skatol had benefits for
      olfactory evaluation in PD patients. Our data also clarified that olfactory
      deficits occurred in a subset of HY I patients. Further prospective study is
      needed to elucidate whether a distinct profile of PD exists between HY I patients
      with and without hyposmia.

PMID- 20689692
TI  - Long term chemoradiotherapy-related dental and skeletal complications in a young
      female with nasopharyngeal carcinoma.
AB  - We describe the long-term complications six years after chemoradiotherapy in a 20
      year old woman with nasopharyngeal carcinoma. We wanted to know whether the
      radiation dose was constant throughout the oral cavity, and thus uniformly
      affecting the corresponding dental and skeletal structures. Clinical and
      radiologic findings are described six years after chemoradiotherapy based on a
      two-dimensional computerized treatment planning system. This revealed radiation
      caries limited only to posterior teeth, proximal caries in the anterior teeth,
      limited but continuous salivary flow, mild periodontal infection, mild
      xerostomia, and a regenerative capacity of bones and the developmental process.
      The quantitative assessment of radiation delivered to the mandible revealed a
      high radiation dose in the posterior area and a minimal dose in the anterior
      area. This explains the differences in caries manifestation between the anterior
      and posterior teeth. According to the present study, individualized radiation
      fields, using a two-dimensional treatment planning system, result in restriction
      of severe damage of the dental and skeletal structures, which usually follows
      chemoradiotherapy. Orthodontic treatment could be initiated according to
      individual patient needs.

PMID- 20689693
TI  - Prenatal diagnosis of fetal hemivertebra at 20 weeks' gestation with literature
      review.
AB  - Hemivertebra is a rare congenital spinal malformation, where only one side of the
      vertebral body develops, resulting in deformation of the spine, such as
      scoliosis, lordosis, or kyphosis. We present the ultrasonographic features of a
      fetus with hemivertebra at 20 weeks' gestation confirmed by post mortem
      radiography and pathological examination. The prenatal literature on this
      disorder is also reviewed. Useful background information is provided for both
      clinicians and other health professionals who are not familiar with this
      condition.

PMID- 20689694
TI  - Patient preference for needleless factor VIII reconstitution device: the Italian
      experience.
AB  - BACKGROUND: Needlestick injuries, mostly due to unsafe needle devices, are a
      frequent adverse event among health care workers and patients on chronic
      treatment, such as hemophiliacs. To improve the safety of these procedures, a
      needleless reconstitution system, Bio-Set((R)) has been implemented for the
      sucrose-formulated recombinant factor VIII (rFVIII-FS) Kogenate((R)) Bayer (Bayer
      Healthcare, Berlin, Germany). The aim of this study was to collect patients'
      satisfaction and safety data regarding the administration of rFVIII-FS with this
      new device. METHODS: This was a multicenter, prospective, postmarketing
      surveillance study collecting data from seven Italian Haemophilia Centers within
      the framework of an international project involving patients from nine European
      countries. The patients were asked to fill out two preference questionnaires (one
      assessing the old method and one assessing the new method) directly after the
      training and two further preference questionnaries (assessing the new method)
      after a period of about 3 and 12 months. RESULTS: A total of 44 male hemophilia A
      patients were included in the analysis. At the end of the 12-month observation
      period, physicians assessed the patients' satisfaction with Kogenate((R)) Bayer
      with Bio-Set((R)) in 40.9% (n = 18) as "very satisfied" and in 45.5% (n = 20) as
      "satisfied", whereas "not satisfied" ratings were given for 9.1% (n = 4) of
      patients (data missing from two patients, 4.5%). The compliance of the patients
      compared with the last method before switch to the Bio-Set((R)) device was rated
      as "better", "equal", and "worse" in 72.7% (n = 32), 20.5% (n = 9), and 2.3% (n =
      1) of patients, respectively. Three patients (6.8%) experienced adverse events,
      but only one event was related to rFVIII infusion (inhibitor development in a
      patient who had little prior exposure to rFVIII) itself and not to the new device
      per se. CONCLUSIONS: The great majority of Italian patients who switched from an
      older method of rFVIII reconstitution to rFVIII-FS with the new reconstitution
      method preferred the new method. The ease of use, perceived safety from
      needlesticks, and the speed of reconstitution were identified as main advantages
      by the majority of patients.

PMID- 20689695
TI  - Treatment of lumbar disc herniation: Evidence-based practice.
AB  - CLINICAL QUESTION: What is the best treatment for lumbar disc herniations?
      RESULTS: For patients failing six weeks of conservative care, the current
      literature supports surgical intervention or prolonged conservative management as
      appropriate treatment options for lumbar radiculopathy in the setting of disc
      herniation. Surgical intervention may result in more rapid relief of symptoms and
      restoration of function. IMPLEMENTATION: While surgery appears to provide more
      rapid relief, many patients will gradually get better with continued nonoperative
      management; thus, patient education and active participation in decision-making
      is vital.

PMID- 20689696
TI  - Development of a sublingual allergy vaccine for grass pollinosis.
AB  - Grass pollen is a very common cause of allergic rhinitis and asthma. The only
      treatment targeting the underlying causes of allergy is immunotherapy (IT).
      Sublingual immunotherapy (SLIT) has been introduced to solve the problem of
      systemic reactions to subcutaneous IT (SCIT). This article evaluates the
      characteristics of the allergen extract, Staloral, in terms of practical
      administration, effectiveness, safety, and mechanism of action. Efficacy data
      were obtained from double-blind, placebo-controlled studies using Staloral in
      patients sensitized to grass pollen, while practical administration, cost
      effectiveness, and mechanism of action data were provided by well designed
      studies. The efficacy and safety of Staloral, as demonstrated by review of
      published studies which used doses up to 1125 times those administered with SCIT,
      shows that this allergen extract has optimal characteristics for treating
      patients with seasonal allergies due to grass pollens. The main mechanism of
      action is the interaction between dendritic cells of the oral mucosa and the
      subsequent tolerance induced in T-cells.

PMID- 20689697
TI  - Evidence supporting the use of recombinant activated factor VII in congenital
      bleeding disorders.
AB  - BACKGROUND: Recombinant activated factor VII (rFVIIa, NovoSeven) was introduced
      in 1996 for the treatment of hemophilic patients with antibodies against
      coagulation factor VIII or IX. OBJECTIVE: To review the evidence supporting the
      use of rFVIIa for the treatment of patients with congenital bleeding disorders.
      PATIENTS AND METHODS: English-language databases were searched in September 2009
      for reports of randomized controlled trials (RCTs) evaluating the ability of
      rFVIIa to restore hemostasis in patients with congenital bleeding disorders.
      RESULTS: Eight RCTs involving 256 hemophilic patients with antibodies against
      coagulation factors, also known as inhibitors, were identified. The evidence
      supporting the use of rFVIIa in these patients was weak with regard to dose,
      clinical setting, mode of administration, efficacy, and adverse events, given the
      limited sample size of each RCT and the heterogeneity of the studies. CONCLUSION:
      The authors suggest that rFVIIa therapy in hemophilic patients with inhibitors
      should be based on the individual's ability to generate thrombin and form a clot,
      and not on the patient's weight alone. Therefore, assays for thrombin generation,
      such as whole-blood thromboelastography, have the potential to significantly
      improve the treatment of these patients.

PMID- 20689698
TI  - Identification of targets and new developments in the treatment of multiple
      sclerosis--focus on cladribine.
AB  - Orally available disease-modifying drugs for relapsing-remitting multiple
      sclerosis (MS) represent an unmet need for this chronic and debilitating disease.
      Among 5 currently investigated drugs at phase 3 clinical stage, promising
      efficacy data for fingolimod and oral cladribine have recently been published.
      However, benefits need to be weighed against the risks to define the role of
      these compounds within current treatment regimens. In this review, data on the
      efficacy of a promising compound, oral cladribine, are discussed and balanced
      with known and anticipated risks in a postmarketing era, and finally gives an
      outlook on the potential place of this drug in treatment algorithms for MS in the
      future.

PMID- 20689699
TI  - Optimal use of recombinant factor VIIa in the control of bleeding episodes in
      hemophilic patients.
AB  - One of the last remaining clinical hurdles in the treatment of people with
      hemophilia is the development of inhibitors. Alloantibodies or autoantibodies
      directed at coagulation factors render the infusion of coagulation factor
      concentrates ineffective, and alternative means must be used to achieve
      hemostasis. Recombinant factor VIIa (rFVIIa) was developed to control bleeding
      episodes in hemophilic patients with inhibitors. Clinical efficacy in achieving
      hemostasis in inhibitor patients was demonstrated by a compassionate-use
      protocol, as well as in randomized controlled trials. To date, over 1.5 million
      doses of rFVIIa have been given to inhibitor patients, with an excellent efficacy
      and safety record. Because of its short half-life, alternative means of dosing
      and infusing rFVIIa have been explored and are reviewed here.

PMID- 20689700
TI  - Glucose regulation of thrombospondin and its role in the modulation of smooth
      muscle cell proliferation.
AB  - Smooth muscle cells (SMC) maintained in high glucose are more responsive to IGF-I
      than those in normal glucose. There is significantly more thrombospondin-1 (TSP
      1) in extracellular matrix surrounding SMC grown in 25 mM glucose. In this study
      we investigated 1) the mechanism by which glucose regulates TSP-1 levels and 2)
      the mechanism by which TS-1 enhances IGF-I signaling. The addition of TSP-1 to
      primary SMC was sufficient to enhance IGF-I responsiveness in normal glucose.
      Reducing TSP-1 protein levels inhibited IGF-I signaling in SMC maintained in high
      glucose. We determined that TSP-1 protected IAP/CD47 from cleavage and thereby
      facilitated its association with SHP substrate-1 (SHPS-1). We have shown
      previously that the hyperglycemia induced protection of IAP from cleavage is an
      important component of the ability of hyperglycemia to enhance IGF-I signaling.
      Furthermore we determined that TSP-1 also enhanced phosphorylation of the beta3
      subunit of the alphaVbeta3 integrin, another molecular event that we have shown
      are critical for SMC response to IGF-I in high glucose. Our studies also revealed
      that the difference in the amount of TSP-1 in the two different glucose
      conditions was due, at least in part, to a difference in the cellular uptake and
      degradation of TSP-1.

PMID- 20689701
TI  - Compressed sensing inspired image reconstruction from overlapped projections.
AB  - The key idea discussed in this paper is to reconstruct an image from overlapped
      projections so that the data acquisition process can be shortened while the image
      quality remains essentially uncompromised. To perform image reconstruction from
      overlapped projections, the conventional reconstruction approach (e.g., filtered
      backprojection (FBP) algorithms) cannot be directly used because of two problems.
      First, overlapped projections represent an imaging system in terms of summed
      exponentials, which cannot be transformed into a linear form. Second, the
      overlapped measurement carries less information than the traditional line
      integrals. To meet these challenges, we propose a compressive sensing-(CS-) based
      iterative algorithm for reconstruction from overlapped data. This algorithm
      starts with a good initial guess, relies on adaptive linearization, and minimizes
      the total variation (TV). Then, we demonstrated the feasibility of this algorithm
      in numerical tests.

PMID- 20689702
TI  - Chromatography-olfactometry study of the aroma of fino sherry wines.
AB  - The aroma of Fino sherry wines produced by industrial biological aging for 0,
      1.5, 2.5, 4.5, and 6 years in the Montilla-Moriles region (southern Spain) was
      studied by gas chromatography-olfactometry. The aroma sensations detected by 3
      trained sniffers were classified according to their odor descriptors into 8
      odorant series (fruity, empyreumatic, chemical, fatty, balsamic, vegetable,
      floral, and spicy), describing the aroma profile of the studied wines. The
      results showed 47 detected odors in the unaged wines, 50 in the 1.5-years-old
      wines and 59, 61 and 69 in the wines aged 2.5, 4.5, and 6 years, respectively.
      According to the frequency of the perceived aromas, the fruity and empyreumatic
      series were the most characteristic odorant series. By exception of chemical,
      floral and balsamic series without changes during aging of the wines, the
      remainder series increased their participation during the aging, mainly the
      fruity, empyreumatic, and fatty series.

PMID- 20689703
TI  - Zinc Binding Properties of Engineered RING Finger Domain of Arkadia E3 Ubiquitin
      Ligase.
AB  - Human Arkadia is a nuclear protein consisted of 989 amino acid residues, with a
      characteristic RING domain in its C-terminus. The RING domain harbours the E3
      ubiquitin ligase activity needed by Arkadia to ubiquitinate its substrates such
      as negative regulators of TGF-beta signaling. The RING finger domain of Arkadia
      is a RING-H2 type and its structure and stability is strongly dependent on the
      presence of two bound Zn(II) ions attached to the protein frame through a defined
      Cys3-His2-Cys3 motif. In the present paper we transform the RING-H2 type of
      Arkadia finger domain to nonnative RING sequence, substituting the zinc-binding
      residues Cys(955) or His(960) to Arginine, through site-directed mutagenesis. The
      recombinant expression, in Escherichia coli, of the mutants C955R and H960R
      reveal significant lower yield in respect with the native polypeptide of Arkadia
      RING-H2 finger domain. In particular, only the C955R mutant exhibits expression
      yield sufficient for recombinant protein isolation and preliminary studies.
      Atomic absorption measurements and preliminary NMR data analysis reveal that the
      C955R point mutation in the RING Finger domain of Arkadia diminishes dramatically
      the zinc binding affinity, leading to the breakdown of the global structural
      integrity of the RING construct.

PMID- 20689704
TI  - Interactions of Trivalent Lanthanide Cations with a New Hexadentate Di-Schiff
      Base: New Lanthanide(III) Complexes from (NE,N'E)-2,2'-(ethane-1,2
      diylbis(oxy))bis(N-(pyridin-2-ylmethylene)ethanamine).
AB  - The novel lanthanide(III) complexes [Ln(NO(3))(2)L](NO(3)).3MeOH (Ln = La 1, Pr
      2) and [Ln(NO(3))(3)L](NO(3)).2MeOH (Ln = Gd 3, Yb 4), where L = (NE,N'E)-2,2'
      (ethane-1,2-diylbis(oxy))bis(N-(pyridin-2-ylmethylene)ethanamine), have been
      obtained by direct reaction of the Schiff base ligand and the corresponding
      hydrated lanthanide(III) nitrates in methanol. All complexes were characterized
      spectroscopically and thermogravimetrically. Complex 4 was also characterized
      with crystallographic studies: orthorhombic P2(1)2(1)2(1), a = 10.6683(14), b =
      13.4752(15), c = 19.3320(26) A. In the molecular structure of 4, Yb(III) is
      surrounded by all donor atoms of the Schiff base (four nitrogen and two oxygen
      atoms) and four oxygen atoms belonging to two bidentate chelating nitrato
      ligands.

PMID- 20689705
TI  - Qualitative simulation of photon transport in free space based on monte carlo
      method and its parallel implementation.
AB  - During the past decade, Monte Carlo method has obtained wide applications in
      optical imaging to simulate photon transport process inside tissues. However,
      this method has not been effectively extended to the simulation of free-space
      photon transport at present. In this paper, a uniform framework for noncontact
      optical imaging is proposed based on Monte Carlo method, which consists of the
      simulation of photon transport both in tissues and in free space. Specifically,
      the simplification theory of lens system is utilized to model the camera lens
      equipped in the optical imaging system, and Monte Carlo method is employed to
      describe the energy transformation from the tissue surface to the CCD camera.
      Also, the focusing effect of camera lens is considered to establish the
      relationship of corresponding points between tissue surface and CCD camera.
      Furthermore, a parallel version of the framework is realized, making the
      simulation much more convenient and effective. The feasibility of the uniform
      framework and the effectiveness of the parallel version are demonstrated with a
      cylindrical phantom based on real experimental results.

PMID- 20689706
TI  - Hydrogen-Bonded Networks Based on Cobalt(II), Nickel(II), and Zinc(II) Complexes
      of N,N'-Diethylurea.
AB  - N,N'-diethylurea (DEU) was employed as a ligand to form the octahedral complexes
      [M(DEU)(6)](2+) (M=Co, Ni and Zn). Compounds [Co(DEU)(6)](BF(4))(2) (1),
      [Co(DEU)(6)](CIO(4))(2) (2), [Ni(DEU)(6)](CIO(4))(2) (3), and
      [Zn(DMU)(6)](CIO(4))(2) (4) have been prepared from the reactions of DEU and the
      appropriate hydrated metal(II) salts in EtOH in the presence of 2,2
      dimethoxypropane. Crystal structure determinations demonstrate the existence of
      [M(DEU)(6)](2+) cations and CIO(4) (-) (in 2-4) or BF(4) (-) (in 1) counterions.
      The [M(DEU)(6)](2+) cations in the solid state are stabilized by a pseudochelate
      effect due to the existence of six strong intracationic N-H cdots, three dots,
      centered O((DEU)) hydrogen bonds. The [M(DEU)(6)](2+) cations and counterions
      self-assemble to form hydrogen-bonded 2D architectures in 2-4 that conform to the
      kgd (kagome dual) network, and a 3D hydrogen-bonded rtl (rutile) network in 1.
      The nature of the resulting supramolecular structures is influenced by the nature
      of the counter-ion. The complexes were also characterized by vibrational
      spectroscopy (IR).

PMID- 20689707
TI  - Measuring the cytochrome C nitrite reductase activity-practical considerations on
      the enzyme assays.
AB  - The cytochrome c nitrite reductase (ccNiR) from Desulfovibrio desulfuricans ATCC
      27774 is able to reduce nitrite to ammonia in a six-electron transfer reaction.
      Although extensively characterized from the spectroscopic and structural points
      of-view, some of its kinetic aspects are still under explored. In this work the
      kinetic behaviour of ccNiR has been evaluated in a systematic manner using two
      different spectrophotometric assays carried out in the presence of different
      redox mediators and a direct electrochemical approach. Solution assays have
      proved that the specific activity of ccNiR decreases with the reduction potential
      of the electronic carriers and ammonium is always the main product of nitrite
      reduction. The catalytic parameters were discussed on the basis of the mediator
      reducing power and also taking into account the location of their putative
      docking sites with ccNiR. Due to the fast kinetics of ccNiR, electron delivering
      from reduced electron donors is rate-limiting in all spectrophotometric assays,
      so the estimated kinetic constants are apparent only. Nevertheless, this
      limitation could be overcome by using a direct electrochemical approach which
      shows that the binding affinity for nitrite decreases whilst turnover increases
      with the reductive driving force.

PMID- 20689708
TI  - Indications and early outcomes for total pancreatectomy at a high-volume pancreas
      center.
AB  - BACKGROUND: This study aimed to analyse the most common current indications for
      total pancreatectomy (TP) at a high-volume pancreas center. METHOD: Prospectively
      collected data on indications and short-term outcome of all TP's performed from
      January 2004 until June 2008 were analysed. RESULTS: The total pancreatectomies
      (TP) were 63, i.e., 6.7% of all pancreatic procedures (n = 948). Indications for
      TP were classified into 4 groups: tumors of advanced stage, n = 23 (36.5%),
      technical problems due to soft pancreatic tissue, n = 18 (28.6%), troubles due to
      perioperative surgical complications, n = 15 (23.8%), and therapy-resistant pain
      due to chronic pancreatitis, n = 7 (11.1%). Surgical complications occurred in 23
      patients (36.5%). The mortality in elective TP was 6.25%. Median postoperative
      stay was 21 days. Mortality, morbidity and the other perioperative parameters
      differed substantially according to the indication for pancreatectomy.
      CONCLUSION: Total pancreatectomy is definitely indicated for a limited range of
      elective and emergency situations. Indications can be: size or localisation of
      pancreatic tumor, trouble, technical diffuculties and therapy-refractory pain in
      chronic pancreatitis. A TP due to perioperative complications (troubles) after
      pancreatic resections is doomed by extremely high morbidity and mortality and
      should be avoided.

PMID- 20689709
TI  - Structurally diverse metal coordination compounds, bearing imidodiphosphinate and
      diphosphinoamine ligands, as potential inhibitors of the platelet activating
      factor.
AB  - Metal complexes bearing dichalcogenated imidodiphosphinate [R(2)P(E)NP(E)R(2)'](
      ) ligands (E = O, S, Se, Te), which act as (E,E) chelates, exhibit a remarkable
      variety of three-dimensional structures. A series of such complexes, namely,
      square-planar [Cu{(OPPh(2))(OPPh(2))N-O, O}(2)], tetrahedral
      [Zn{(EPPh(2))(EPPh(2))N-E,E}(2)], E = O, S, and octahedral
      [Ga{(OPPh(2))(OPPh(2))N-O,O}(3)], were tested as potential inhibitors of either
      the platelet activating factor (PAF)- or thrombin-induced aggregation in both
      washed rabbit platelets and rabbit platelet rich plasma. For comparison, square
      planar [Ni{(Ph(2)P)(2)N-S-CHMePh-P, P}X(2)], X = Cl, Br, the corresponding metal
      salts of all complexes and the (OPPh(2))(OPPh(2))NH ligand were also
      investigated. Ga(O,O)(3) showed the highest anti-PAF activity but did not inhibit
      the thrombin-related pathway, whereas Zn(S,S)(2), with also a significant PAF
      inhibitory effect, exhibited the highest thrombin-related inhibition. Zn(O,O)(2)
      and Cu(O,O)(2) inhibited moderately both PAF and thrombin, being more effective
      towards PAF. This work shows that the PAF-inhibitory action depends on the
      structure of the complexes studied, with the bulkier Ga(O,O)(3) being the most
      efficient and selective inhibitor.

PMID- 20689710
TI  - A New-Fangled FES-k-Means Clustering Algorithm for Disease Discovery and Visual
      Analytics.
AB  - The central purpose of this study is to further evaluate the quality of the
      performance of a new algorithm. The study provides additional evidence on this
      algorithm that was designed to increase the overall efficiency of the original k
      means clustering technique-the Fast, Efficient, and Scalable k-means algorithm
      (FES-k-means). The FES-k-means algorithm uses a hybrid approach that comprises
      the k-d tree data structure that enhances the nearest neighbor query, the
      original k-means algorithm, and an adaptation rate proposed by Mashor. This
      algorithm was tested using two real datasets and one synthetic dataset. It was
      employed twice on all three datasets: once on data trained by the innovative MIL
      SOM method and then on the actual untrained data in order to evaluate its
      competence. This two-step approach of data training prior to clustering provides
      a solid foundation for knowledge discovery and data mining, otherwise unclaimed
      by clustering methods alone. The benefits of this method are that it produces
      clusters similar to the original k-means method at a much faster rate as shown by
      runtime comparison data; and it provides efficient analysis of large geospatial
      data with implications for disease mechanism discovery. From a disease mechanism
      discovery perspective, it is hypothesized that the linear-like pattern of
      elevated blood lead levels discovered in the city of Chicago may be spatially
      linked to the city's water service lines.

PMID- 20689711
TI  - The Catalytic Function of Nonheme Iron (III) Complex for Hydrocarbon Oxidation.
AB  - A detailed catalytic study of LFe(III)Cl (where L = 3-{2-[2-(3-hydroxy-1,3
      diphenyl-allylideneamino)-ethylamino]-ethylimino}-1,3-diphenyl-propen-1-ol) for
      hydrocarbon oxidation was carried out, focusing on the role of solvent,
      atmospheric dioxygen, and oxidant on catalytic efficiency. The data showed that
      LFe(III)Cl catalyst was efficient in homogeneous hydrocarbon oxidations providing
      significant yields. Moreover, tert-BuOOH provided comparable oxidation yields
      with H(2)O(2), slightly favoring the formation of alcohols and ketones versus
      epoxides. Dioxygen intervened in the catalytic reaction, influencing the nature
      of oxidation products. The polarity of solvent strongly influenced the reaction
      rates and the nature of oxidation products. A mechanistic model is postulated
      assuming that LFe(III)Cl functions via the formation of iron-hydroperoxo-species,
      followed by a radical-based mechanistic path.

PMID- 20689713
TI  - Diorganotin complexes of a thiosemicarbazone, synthesis: properties, x-ray
      crystal structure, and antiproliferative activity of diorganotin complexes.
AB  - The synthesis and spectral characterization of novel diorganotin complexes with 3
      hydroxypyridine-2-carbaldehyde thiosemicarbazone, H(2)L(1), [SnMe(2)(L)] (2),
      [SnBu(2)(L)] (3), and [SnPh(2)(L)] (4) are reported. The single-crystal X-ray
      structure of complex [SnPh(2)(L)(DMSO)] (5) shows that the ligand is doubly
      deprotonated and is coordinated as tridentate ligand. The six coordination number
      is completed by two carbon atoms of phenyl groups. There are two similar monomers
      5a (Sn1) and 5b (Sn51) in the asymmetric unit. The monomers 5a and 5b are linked
      through intermolecular hydrogen bonds of N-H-O and C-H-S type. C-H --> pi,
      intermolecular interactions, intra- and intermolecular hydrogen bonds stabilize
      this structure and leads to aggregation and a supramolecular assembly. The IR and
      NMR ((1)H, (13)C and (119)Sn) spectroscopic data of the complexes are reported.
      The in vitro cytotoxic activity has been evaluated against the cells of three
      human cancer cell lines: MCF-7 (human breast cancer cell line), T-24 (bladder
      cancer cell line), A-549 (nonsmall cell lung carcinoma) and a mouse L-929 (a
      fibroblast-like cell line cloned from strain L). Compounds 1, 3, and 4 were found
      active against all four cell lines. Selectivity was observed for complexes 3 and
      4 which were found especially active against MCF-7 and T-24 cancer cell lines.

PMID- 20689712
TI  - Hybrid ICA-Seed-Based Methods for fMRI Functional Connectivity Assessment: A
      Feasibility Study.
AB  - Brain functional connectivity (FC) is often assessed from fMRI data using seed
      based methods, such as those of detecting temporal correlation between a
      predefined region (seed) and all other regions in the brain; or using
      multivariate methods, such as independent component analysis (ICA). ICA is a
      useful data-driven tool, but reproducibility issues complicate group inferences
      based on FC maps derived with ICA. These reproducibility issues can be
      circumvented with hybrid methods that use information from ICA-derived spatial
      maps as seeds to produce seed-based FC maps. We report results from five
      experiments to demonstrate the potential advantages of hybrid ICA-seed-based FC
      methods, comparing results from regressing fMRI data against task-related a
      priori time courses, with "back-reconstruction" from a group ICA, and with five
      hybrid ICA-seed-based FC methods: ROI-based with (1) single-voxel, (2) few-voxel,
      and (3) many-voxel seed; and dual-regression-based with (4) single ICA map and
      (5) multiple ICA map seed.

PMID- 20689714
TI  - In Search for Titanocene Complexes with Improved Cytotoxic Activity: Synthesis, X
      Ray Structure, and Spectroscopic Study of Bis(eta
      cyclopentadienyl)difluorotitanium(IV).
AB  - The 1 : 2 reaction of [Ti(eta(5)-C(5)H(5))(2)Cl(2)] and AgF in CHCl(3)/H(2)O
      yielded the fluoro analog [Ti(eta(5)-C(5)H(5))(2)F(2)] (1) in almost quantitative
      yield (C(5)H(5) is the cyclopentadienyl group). The coordination about the Ti(IV)
      atom formed by two fluoro ligands and the centroids of the cyclopentadienyl rings
      is distorted tetrahedral. The compound crystallizes in the orthorhombic space
      group C2cm. The lattice constants are a = 5.9055(4), b = 10.3021(5), c =
      14.2619(9) A, and alpha = beta = gamma = 90 degrees . The complex has been
      characterized by elemental analyses and spectroscopic (IR, (1)H NMR) data. A
      structural comparison of the four members of the [Ti(eta(5)-C(5)H(5))(2)X(2)]
      family of complexes (X = F, Cl, Br, I) is attempted.

PMID- 20689715
TI  - Studies of the Antiproliferative Activity of Ruthenium (II) Cyclopentadienyl
      Derived Complexes with Nitrogen Coordinated Ligands.
AB  - Four cationic ruthenium(II) complexes with the formula [Ru(eta(5)
      C(5)H(5))(PPh(3))(2)](+), with L = 5-phenyl-1H-tetrazole (TzH) 1, imidazole (ImH)
      2, benzo[1,2-b;4,3-b'] dithio-phen-2-carbonitrile (Bzt) 3, and [5-(2-thiophen-2
      yl)-vinyl]-thiophene-2-carbonitrile] (Tvt) 4 were prepared and characterized in
      view to evaluate their potentialities as antitumor agents. Studies by Circular
      Dichroism indicated changes in the secondary structure of ct-DNA. Changes in the
      tertiary structure of pBR322 plasmid DNA were also observed in gel
      electrophoresis experiment and the images obtained by atomic force microscopy
      (AFM) suggest strong interaction with pBR322 plasmid DNA; the observed decreasing
      of the viscosity with time indicates that the complexes do not intercalate
      between DNA base pairs. Compounds 1, 2, and 3 showed much higher cytotoxicity
      than the cisplatin against human leukaemia cancer cells (HL-60 cells).

PMID- 20689716
TI  - New thermal and microbial resistant metal-containing epoxy polymers.
AB  - A series of metal-containing epoxy polymers have been synthesized by the
      condensation of epichlorohydrin (1-chloro-2,3-epoxy propane) with Schiff base
      metal complexes in alkaline medium. Schiff base was initially prepared by the
      reaction of 2,6 dihydroxy 1-napthaldehyde and o-phenylenediamine in 1 : 2 molar
      ratio and then with metal acetate. All the synthesized compounds were
      characterized by elemental, spectral, and thermal analysis. The physicochemical
      properties, viz., epoxy value, hydroxyl content, and chlorine content [mol/100 g]
      were measured by standard procedures. The antimicrobial activities of these metal
      containing epoxy polymers were carried out by using minimum inhibitory
      concentration (MIC) and minimum bactericidal concentration (MBC) methods against
      S. aureus, B. subtilis (Gram-positive bacteria), and E. coli, P. aeruginosa (Gram
      negative bacteria). It was found that the ECu(II) showed higher antibacterial
      activity than other metal-chelated epoxy resin while EMn(II) exhibited reduced
      antibacterial activity against all bacteria.

PMID- 20689717
TI  - Prefrontal Cortex Modulation during Anticipation of Working Memory Demands as
      Revealed by Magnetoencephalography.
AB  - During the anticipation of task demands frontal control is involved in the
      assembly of stimulus-response mappings based on current goals. It is not clear
      whether prefrontal modulations occur in higher-order cortical regions, likely
      reflecting cognitive anticipation processes. The goal of this paper was to
      investigate prefrontal modulation during anticipation of upcoming working memory
      demands as revealed by magnetoencephalography (MEG). Twenty healthy volunteers
      underwent MEG while they performed a variation of the Sternberg Working Memory
      (WM) task. Beta band (14-30 Hz) SAM (Synthetic Aperture Magnetometry) analysis
      was performed. During the preparatory periods there was an increase in beta power
      (event-related synchronization) in dorsolateral prefrontal cortex (DLPFC)
      bilaterally, left inferior prefrontal gyrus, left parietal, and temporal areas.
      Our results provide support for the hypothesis that, during preparatory states,
      the prefrontal cortex is important for biasing higher order brain regions that
      are going to be engaged in the upcoming task.

PMID- 20689718
TI  - Single-Tooth Modeling for 3D Dental Model.
AB  - An integrated single-tooth modeling scheme is proposed for the 3D dental model
      acquired by optical digitizers. The cores of the modeling scheme are fusion
      regions extraction, single tooth shape restoration, and single tooth separation.
      According to the "valley" shape-like characters of the fusion regions between two
      adjoining teeth, the regions of the 3D dental model are analyzed and classified
      based on the minimum curvatures of the surface. The single tooth shape is
      restored according to the bioinformation along the hole boundary, which is
      generated after the fusion region being removed. By using the extracted boundary
      from the blending regions between the teeth and soft tissues as reference, the
      teeth can be separated from the 3D dental model one by one correctly.
      Experimental results show that the proposed method can achieve satisfying
      modeling results with high-degree approximation of the real tooth and meet the
      requirements of clinical oral medicine.

PMID- 20689719
TI  - Production of Pectate Lyase by Penicillium viridicatum RFC3 in Solid-State and
      Submerged Fermentation.
AB  - Pectate lyase (PL) was produced by the filamentous fungus Penicillium viridicatum
      RFC3 in solid-state cultures of a mixture of orange bagasse and wheat bran (1 : 1
      w/w), or orange bagasse, wheat bran and sugarcane bagasse (1 : 1 : 0.5 w/w), and
      in a submerged liquid culture with orange bagasse and wheat bran (3%) as the
      carbon source. PL production was highest (1,500 U mL(-1) or 300 Ug(-1) of
      substrate) in solid-state fermentation (SSF) on wheat bran and orange bagasse at
      96 hours. PL production in submerged fermentation (SmF) was influenced by the
      initial pH of the medium. With the initial pH adjusted to 4.5, 5.0, and 5.5, the
      peak activity was observed after 72, 48, and 24 hours of fermentation,
      respectively, when the pH of the medium reached the value 5.0. PL from SSF and
      SmF were loaded on Sephadex-G75 columns and six activity peaks were obtained from
      crude enzyme from SSF and designated PL I, II, III, IV, V, and VI, while five
      peaks were obtained from crude enzyme from SmF and labeled PL I', II', III', IV',
      and VII'. Crude enzyme and fraction III from each fermentative process were
      tested further. The optimum pH for crude PL from either process was 5.5, while
      that for PL III was 8.0. The maximum activity of enzymes from SSF was observed at
      35 degrees C, but crude enzyme was more thermotolerant than PL III, maintaining
      its maximum activity up to 45 degrees C. Crude enzyme from SmF and PL III' showed
      thermophilic profiles of activity, with maximum activity at 60 and 55 degrees C,
      respectively. In the absence of substrate, the crude enzyme from SSF was stable
      over the pH range 3.0-10.0 and PL III was most stable in the pH range 4.0-7.0.
      Crude enzyme from SmF retained 70%-80% of its maximum activity in the acid
      neutral pH range (4.0-7.0), but PIII showed high stability at alkaline pH (7.5
      9.5). PL from SSF was more thermolabile than that from SmF. The latter maintained
      60% of its initial activity after 1 h at 55 degrees C. The differing behavior of
      the enzymes with respect to pH and temperature suggests that they are different
      isozymes.

PMID- 20689720
TI  - Autism and Anthropology?

PMID- 20689721
TI  - Grouping pursuit through a regularization solution surface.
AB  - Extracting grouping structure or identifying homogenous subgroups of predictors
      in regression is crucial for high-dimensional data analysis. A low-dimensional
      structure in particular-grouping, when captured in a regression model, enables to
      enhance predictive performance and to facilitate a model's interpretability
      Grouping pursuit extracts homogenous subgroups of predictors most responsible for
      outcomes of a response. This is the case in gene network analysis, where grouping
      reveals gene functionalities with regard to progression of a disease. To address
      challenges in grouping pursuit, we introduce a novel homotopy method for
      computing an entire solution surface through regularization involving a piecewise
      linear penalty. This nonconvex and overcomplete penalty permits adaptive grouping
      and nearly unbiased estimation, which is treated with a novel concept of grouped
      subdifferentials and difference convex programming for efficient computation.
      Finally, the proposed method not only achieves high performance as suggested by
      numerical analysis, but also has the desired optimality with regard to grouping
      pursuit and prediction as showed by our theoretical results.

PMID- 20689722
TI  - Children's Security in the Context of Family Instability and Maternal
      Communications.
AB  - This multi-method study examined the association between family instability and
      children's internal representations of security in the family system within the
      context of maternal communications about disruptive family events. Participants
      included 224 kindergarten children (100 boys and 124 girls) and their parents.
      Parents reported on the frequency of unstable family events, mothers reported
      their patterns of communication to children following disruptive events, and
      children completed a story-stem battery to assess their internal representations
      of family security. Consistent with predictions, heightened family instability
      was associated with less security in child representations. The implication of
      these results for notions of children's security in the family system, including
      exploratory findings on the protective role of maternal communications for
      children's representations, are discussed.

PMID- 20689723
TI  - The Moving Boundary Node Method: A level set-based, finite volume algorithm with
      applications to cell motility.
AB  - Eukaryotic cell crawling is a highly complex biophysical and biochemical process,
      where deformation and motion of a cell are driven by internal, biochemical
      regulation of a poroelastic cytoskeleton. One challenge to building quantitative
      models that describe crawling cells is solving the reaction-diffusion-advection
      dynamics for the biochemical and cytoskeletal components of the cell inside its
      moving and deforming geometry. Here we develop an algorithm that uses the level
      set method to move the cell boundary and uses information stored in the distance
      map to construct a finite volume representation of the cell. Our method preserves
      Cartesian connectivity of nodes in the finite volume representation while
      resolving the distorted cell geometry. Derivatives approximated using a Taylor
      series expansion at finite volume interfaces lead to second order accuracy even
      on highly distorted quadrilateral elements. A modified, Laplacian-based
      interpolation scheme is developed that conserves mass while interpolating values
      onto nodes that join the cell interior as the boundary moves. An implicit time
      stepping algorithm is used to maintain stability. We use the algoirthm to
      simulate two simple models for cellular crawling. The first model uses
      depolymerization of the cytoskeleton to drive cell motility and suggests that the
      shape of a steady crawling cell is strongly dependent on the adhesion between the
      cell and the substrate. In the second model, we use a model for chemical
      signalling during chemotaxis to determine the shape of a crawling cell in a
      constant gradient and to show cellular response upon gradient reversal.

PMID- 20689724
TI  - Chemical Sulfation of Small Molecules - Advances and Challenges.

PMID- 20689725
TI  - Selecting At-Risk First-Grade Readers for Early Intervention: Eliminating False
      Positives and Exploring the Promise of a Two-Stage Gated Screening Process.
AB  - The purposes of this study were (a) to identify measures that when added to a
      base 1(st)-grade screening battery help eliminate false positives and (b) to
      investigate gains in efficiency associated with a 2-stage gated screening
      procedure. We tested 355 children in the fall of 1(st) grade, and assessed for
      reading difficulty at the end of 2(nd) grade. The base screening model, included
      measures of phonemic awareness, rapid naming skill, oral vocabulary, and initial
      word identification fluency (WIF). Short-term WIF progress monitoring (intercept
      and slope), dynamic assessment, running records, and oral reading fluency were
      each considered as an additional screening measure in contrasting models. Results
      indicated that the addition of WIF progress monitoring and dynamic assessment,
      but not running records or oral reading fluency, significantly decreased false
      positives. The 2-stage gated screening process using phonemic decoding efficiency
      in the first stage significantly reduced the number of children requiring the
      full screening battery.

PMID- 20689726
TI  - Ultrafast Time-resolved Absorption Spectroscopy of Geometric Isomers of
      Xanthophylls.
AB  - This paper presents an ultrafast optical spectroscopic investigation of the
      excited state energies, lifetimes and spectra of specific geometric isomers of
      neoxanthin, violaxanthin, lutein, and zeaxanthin. All-trans- and 15,15'-cis-beta
      carotene were also examined. The spectroscopy was done on molecules purified by
      HPLC frozen immediately to inhibit isomerization. The spectra were taken at 77 K
      to maintain the configurations and to provide better spectral resolution than
      seen at room temperature. The kinetics reveal that for all of the molecules
      except neoxanthin, the S(1) state lifetime of the cis-isomers is shorter than
      that of the all-trans isomers. The S(1) excited state energies of all the isomers
      were determined by recording S(1) --> S(2) transient absorption spectra. The
      results obtained in this manner at cryogenic temperatures provide an
      unprecedented level of precision in the measurement of the S(1) energies of these
      xanthophylls, which are critical components in light-harvesting pigment-protein
      complexes of green plants.

PMID- 20689727
TI  - Promoting Optimal Health with Traditional Chinese Medicine.

PMID- 20689728
TI  - Adolescents' heightened risk-seeking in a probabilistic gambling task.
AB  - This study investigated adolescent males' decision-making under risk, and the
      emotional response to decision outcomes, using a probabilistic gambling task
      designed to evoke counterfactually mediated emotions (relief and regret).
      Participants were 20 adolescents (aged 9-11), 26 young adolescents (aged 12-15),
      20 mid-adolescents (aged 15-18) and 17 adults (aged 25-35). All were male. The
      ability to maximize expected value improved with age. However, there was an
      inverted U-shaped developmental pattern for risk-seeking. The age at which risk
      taking was highest was 14.38 years. Although emotion ratings overall did not
      differ across age, there was an increase between childhood and young adolescence
      in the strength of counterfactually mediated emotions (relief and regret)
      reported after receiving feedback about the gamble outcome. We suggest that
      continuing development of the emotional response to outcomes may be a factor
      contributing to adolescents' risky behaviour.

PMID- 20689729
TI  - Modelling the biphasic growth and product formation by Enterococcus faecium CECT
      410 in realkalized fed-batch fermentations in whey.
AB  - The influence of initial pH on growth and nutrient (total sugars, nitrogen, and
      phosphorous) consumption by Enterococcus faecium CECT 410 was studied during
      batch cultures in whey. With these data, two realkalized fed-batch fermentations
      were developed using different feeding substrates. The shift from homolactic to
      mixed acid fermentation, the biphasic kinetics observed for cell growth and
      nitrogen consumption and the increase in the concentrations of biomass and
      products (lactic acid, acetic acid, ethanol, and butane-2,3-diol) were the most
      noteworthy observations of these cultures. Modelling the fed-batch growth of Ent.
      faecium with the Logistic and bi-Logistic models was not satisfactory. However,
      biomass production was best mathematically described with the use of a double
      Monod model, which was expressed in terms of biomass, product accumulation, and
      nitrogen utilization. Product formation was successfully modelled with a modified
      form of the Luedeking and Piret model developed in this study.

PMID- 20689731
TI  - In vivo cytogenetic studies on aspartame.
AB  - Aspartame (a-Laspartyl-L-phenylalanine 1-methylester) is a dipeptide low-calorie
      artificial sweetener that is widely used as a nonnutritive sweetener in foods and
      drinks. The safety of aspartame and its metabolic breakdown products
      (phenylalanine, aspartic acid and methanol) was investigated in vivo using
      chromosomal aberration (CA) test and sister chromatid exchange (SCE) test in the
      bone marrow cells of mice. Swiss Albino male mice were exposed to aspartame (3.5,
      35, 350 mg/kg body weight). Bone marrow cells isolated from femora were analyzed
      for chromosome aberrations and sister chromatid exchanges. Treatment with
      aspartame induced dose dependently chromosome aberrations at all concentrations
      while it did not induce sister chromatid exchanges. On the other hand, aspartame
      did not decrease the mitotic index (MI). However, statistical analysis of the
      results show that aspartame is not significantly genotoxic at low concentration.

PMID- 20689732
TI  - Calculation of the c(3)a percentage in high sulfur clinker.
AB  - The aim of this paper is to clarify the influence of the clinker SO(3) on the
      amount of C(3)A. The calculation of the cement phases percentages is based on the
      research work, Calculation of the Compounds in Portland Cement, published by
      Bogue in 1929 .The usage of high sulphur fuels, industrial wastes, and tires
      changes completely the working condition of Bogue because the assumed phase
      compositions may change. The results prove that increasing the amount of SO(3) in
      the low alkali clinker decreases the percentages of C(3)A due to the high
      incorporation of alumina in the clinker phases mainly C(2)S and C(3)S. The
      correlation is linear till the clinker SO(3) reaches the 2%. Over that the
      influence of the clinker SO(3) became undetectable. A new calculation method for
      the determination of the C(3)A in the high sulphur and low alkali clinker was
      proposed.

PMID- 20689730
TI  - Eicosanoids in the innate immune response: TLR and non-TLR routes.
AB  - The variable array of pattern receptor expression in different cells of the
      innate immune system explains the induction of distinct patterns of arachidonic
      acid (AA) metabolism. Peptidoglycan and mannan were strong stimuli in
      neutrophils, whereas the fungal extract zymosan was the most potent stimulus in
      monocyte-derived dendritic cells since it induced the production of PGE(2),
      PGD(2), and several cytokines including a robust IL-10 response. Zymosan
      activated kappaB-binding activity, but inhibition of NF-kappaB was associated
      with enhanced IL-10 production. In contrast, treatments acting on CREB (CRE
      binding protein), including PGE(2), showed a direct correlation between CREB
      activation and IL-10 production. Therefore, in dendritic cells zymosan induces
      il10 transcription by a CRE-dependent mechanism that involves autocrine secretion
      of PGE(2), thus unraveling a functional cooperation between eicosanoid production
      and cytokine production.

PMID- 20689733
TI  - Cyberknife stereotactic body radiation therapy for nonresectable tumors of the
      liver: preliminary results.
AB  - PURPOSE: Stereotactic body radiation therapy (SBRT) has emerged as a treatment
      option for local tumor control of primary and secondary malignancies of the
      liver. We report on our updated experience with SBRT in patients with non
      resectable tumors of the liver. METHODS: Our first 17 consecutive patients (mean
      age 58.1 years) receiving SBRT for HCC (n = 6), IHC (n = 3), and LM (n = 8) are
      presented. Mean radiation dose was 34 Gy delivered over 1-3 fractions. RESULTS:
      Treated patients had a mean decrease in maximum pretreatment tumor diameter from
      6.9 +/- 4.6 cm to 5.0 +/- 2.1 cm at three months after treatment (P < .05). The
      mean total tumor volume reduction was 44% at six months (P < .05). 82% of all
      patients (14/17) achieved local control with a median follow-up of 8 months. 100%
      of patients with HCC (n = 6) achieved local control. Patients with surgically
      placed fiducial markers had no complications related to marker placement.
      CONCLUSION: Our preliminary results showed that SBRT is a safe and effective
      local treatment modality in selected patients with liver malignancies with
      minimal adverse events. Further studies are needed to define its role in the
      management of these malignancies.

PMID- 20689734
TI  - Screening for group B streptococcus: a private hospital's experience.
AB  - OBJECTIVE: To assess the effect of universal screening and administration of
      intrapartum antibiotic prophylaxis to prevent early-onset neonatal GBS sepsis at
      a private tertiary care hospital since issuance of the 2002 CDC guidelines for
      preventing perinatal GBS disease. METHODS: Retrospective analysis of women
      delivering between January 1, 2003 and December 31, 2004 at a private tertiary
      care hospital in Houston, Texas. The percentage of women screened, GBS positive
      women receiving intrapartum antibiotic prophylaxis, and infants developing early
      onset GBS sepsis were determined. RESULTS: 2,108 women delivered 2,135 infants
      with 1,874 (89%) screened for GBS. Of those screened, 1,322 (71%) tested negative
      and 552 (29%) tested positive for GBS. In this analysis of 2,135 infants, 3 (0.94
      cases/1,000 live births) were diagnosed with invasive GBS sepsis. CONCLUSION:
      High rates of screening of pregnant women for GBS colonization and use of
      intrapartum antibiotic prophylaxis for GBS carriers can be achieved in a private
      tertiary care hospital setting. " SYNOPSIS: High screening rates for group B
      streptococcus in a private tertiary care hospital reduce the incidence of
      maternal and early onset neonatal GBS infection."

PMID- 20689735
TI  - Synthesis and Biological Evaluation of New CRH Analogues.
AB  - A series of 7 new human/rat Corticotropin Releasing Hormone (h/r-CRH) analogues
      were synthesized. The induced alterations include substitution of Phe at position
      12 with D-Phe, Leu at positions 14 and 15 with Aib and Met at positions 21 and 38
      with Cys(Et) and Cys(Pr). The analogues were tested regarding their binding
      affinity to the CRH-1 receptor and their activity which is represented by means
      of percentage of maximum response in comparison to the native molecule. The
      results indicated that the introduction of Aib, or Cys derivatives although
      altering the secondary structure of the molecule, did not hinder receptor
      recognition and binding.

PMID- 20689736
TI  - Correlation between the matrix metalloproteinase-9 activity and chondroitin
      sulfate concentrations in tear fluid after laser in situ keratomileusis.
AB  - AIMS: The aim of the present study was to evaluate the correlation between matrix
      metalloproteinase-9 (MMP-9) and chondroitin sulfate (CS) concentrations in human
      tear fluid following laser in situ keratomileusis (LASIK). METHODS: Twelve eyes
      from six patients who had no ocular complaints except for refractive errors, and
      who had undergone LASIK, were enrolled in this study. We measured the
      concentrations of chondroitin 4 sulfate (C4S), chondroitin 6 sulfate (C6S), and
      MMP-9 activity with an enzyme-linked immunosorbent assay and an enzyme
      immunocapture activity assay preoperatively and postoperatively on days 1 and 4,
      week 1, and at 1 and 3 months. RESULTS: Although the preoperative MMP-9 activity
      and the C4S concentration were highly correlated (r = 0.900; P < 0.001), they
      were not postoperatively correlated at month 1. Although the preoperative MMP-9
      activity and the C6S concentration were highly correlated (r = 0.885; P < 0.001),
      they were not postoperatively correlated at either week 1 or months 1 and 3.
      CONCLUSIONS: The correlation appeared to be collapsed by LASIK, and it did not
      recover to the preoperative score at 3 months post-surgery. Our study indicates
      that the corneal wound healing was not terminated at 3 months following LASIK.

PMID- 20689737
TI  - Choroidal pigmented lesions imaged by ultra-wide-field scanning laser
      ophthalmoscopy with two laser wavelengths (Optomap).
AB  - PURPOSE: Clinical differentiation of choroidal pigmented lesions is sometimes
      difficult. Choroidal melanoma is the most prevalent primary neoplasia among
      malignant ocular tumors, and metastasis often occurs before the primary tumor is
      diagnosed. Therefore, early detection is essential. We investigated the imaging
      properties of clinically diagnosed melanocytic choroidal tumors using a
      nonmydriatic ultra-wide-field scanning laser ophthalmoscope (SLO) with two laser
      wavelengths to distinguish benign from malignant lesions. Repeated standardized
      ultrasound (US) evaluation provided reference standard. METHODS: In a consecutive
      series of 49 patients with clinically diagnosed melanocytic choroidal tumors in
      one eye, 29 had established melanoma (defined by proven growth on repeated US
      follow-up) and 20 had nevi (defined by no malignancy according to clinical, US,
      and growth characteristics for at least 2 years). All patients underwent clinical
      examination, undilated Optomap((R)) (Optos PLC, Dunfermline, Fife, Scotland, UK)
      imaging, standardized US examination, and standard retinal photography.
      Measurements of the tumor base using the Optomap software were compared with US B
      scan measurements. Imaging characteristics from the SLO images were correlated
      with the structural findings in the two patient groups. RESULTS: Measurements of
      tumor base correlated well between SLO and US with r = 0.61 (T-direction) and r =
      0.51 (L-direction). On SLO imaging, typical malignant lesions appeared dark on
      the red laser channel and bright on the green laser channel. Based on those
      simple binary characteristics, a sensitivity of 76% at a specificity of 70% was
      obtained for a correct classification of lesions. When analogous to clinical
      examination lesion size, margin touching the optic disc, and existence of
      subretinal fluid were additionally considered, 90% sensitivity at 82% specificity
      was obtained. CONCLUSIONS: In this first, limited series, nonmydriatic SLO
      imaging with two laser wavelengths permitted to differentiate malignant ocular
      tumors from nonmalignant lesions with high diagnostic accuracy. Additional
      parameters may further enhance diagnostic properties, but larger patient series
      are required to validate our findings and prove the diagnostic properties.

PMID- 20689738
TI  - Kyrieleis' vasculitis in acute retinal necrosis.
AB  - We report the first case in the literature of Kyrieleis' vasculitis related to
      acute retinal necrosis by Varicella zoster virus in a 76-year-old woman with
      bilateral involvement. In our patient the arterial lesions appeared 15 days after
      the initial presentation.

PMID- 20689739
TI  - Efficacy of amniotic membrane-assisted bleb revision for elevated intraocular
      pressure after filtering surgery.
AB  - PURPOSE: To compare the effectiveness of standard revision surgery using
      mitomycin C (MMC) with revision using amniotic membrane transplantation and MMC
      for elevated intraocular pressure (IOP) after trabeculectomy. PATIENTS AND
      METHODS: A retrospective, nonrandomized comparative study of 36 eyes of 36
      patients with a failed trabeculectomy. Patients were divided into two groups, ie,
      a nonamnion-transplanted group and an amnion-transplanted group. The amniotic
      membrane was placed on the scleral flap under the conjunctiva in the amnion
      transplanted group. Both groups recovered filtration of aqueous humor from the
      surgical site with the adjunctive use of MMC. The changes in IOP and cumulative
      survival rate were compared for the two groups. Success was defined as a 30%
      reduction in IOP from the preoperative IOP and maintenance below 21 mmHg with or
      without the use of antiglaucomatous agents. RESULTS: The mean preoperative IOP
      was not significantly different in the two groups. The mean postoperative IOP in
      the nonamnion group, 12.1 +/- 5.5 mmHg, was significantly lower than the IOP in
      the amnion group, 16.0 +/- 3.7 mmHg. Survival curves in the two groups did not
      reach significantly different levels. CONCLUSIONS: Conventional surgical bleb
      revision with MMC can significantly reduce the elevated IOP associated with a
      failed filtration bleb. The use of an amniotic membrane transplant did not
      improve the surgical outcome in our cases.

PMID- 20689740
TI  - The path dependency theory: analytical framework to study institutional
      integration. The case of France.
AB  - BACKGROUND: The literature on integration indicates the need for an enhanced
      theorization of institutional integration. This article proposes path dependence
      as an analytical framework to study the systems in which integration takes place.
      PURPOSE: PRISMA proposes a model for integrating health and social care services
      for older adults. This model was initially tested in Quebec. The PRISMA France
      study gave us an opportunity to analyze institutional integration in France.
      METHODS: A qualitative approach was used. Analyses were based on semi-structured
      interviews with actors of all levels of decision-making, observations of advisory
      board meetings, and administrative documents. RESULTS: Our analyses revealed the
      complexity and fragmentation of institutional integration. The path dependency
      theory, which analyzes the change capacity of institutions by taking into account
      their historic structures, allows analysis of this situation. The path dependency
      to the Bismarckian system and the incomplete reforms of gerontological policies
      generate the coexistence and juxtaposition of institutional systems. In such a
      context, no institution has sufficient ability to determine gerontology policy
      and build institutional integration by itself. CONCLUSION: Using path dependence
      as an analytical framework helps to understand the reasons why institutional
      integration is critical to organizational and clinical integration, and the
      complex construction of institutional integration in France.

PMID- 20689741
TI  - ASM Launches mBio.

PMID- 20689742
TI  - Mixed infections and In Vivo evolution in the human fungal pathogen Cryptococcus
      neoformans.
AB  - Koch's postulates are criteria establishing a causal relationship between a
      microbe and a disease that lead to the assumption that diseases are caused by a
      single strain or its evolved forms. Cryptococcus neoformans is a life-threatening
      human fungal pathogen responsible for an estimated 1 million cases of
      cryptococcosis/year, predominantly meningoencephalitis. To assess the molecular
      diversity of clinical isolates and gain knowledge of C. neoformans biology in the
      host, we analyzed clinical cultures collected during the prospective CryptoA/D
      study. Using molecular analysis of unpurified isolates, we demonstrated that
      mixed infections in humans are more common than previously thought, occurring in
      almost 20% of patients diagnosed with cryptococcosis. These mixed infections are
      composed of different mating types, serotypes, and/or genotypes. We also
      identified genetically related haploid and diploid strains in the same patients.
      Experimental infections and quantitative PCR show that these ploidy changes can
      result from endoreplication (duplication of DNA content) and that shuttling
      between haploid and diploid states can occur, suggesting in vivo evolution. Thus,
      the concept of one strain/one infection does not hold true for C. neoformans and
      may apply to other environmentally acquired fungal pathogens. Furthermore, the
      possibility of mixed and/or evolving infections should be taken into account when
      developing therapeutic strategies against these pathogens.

PMID- 20689743
TI  - Role of an expanded inositol transporter repertoire in Cryptococcus neoformans
      sexual reproduction and virulence.
AB  - Cryptococcus neoformans and Cryptococcus gattii are globally distributed human
      fungal pathogens and the leading causes of fungal meningitis. Recent studies
      reveal that myo-inositol is an important factor for fungal sexual reproduction.
      That C. neoformans can utilize myo-inositol as a sole carbon source and the
      existence of abundant inositol in the human central nervous system suggest that
      inositol is important for Cryptococcus development and virulence. In accord with
      this central importance of inositol, an expanded myo-inositol transporter (ITR)
      gene family has been identified in Cryptococcus. This gene family contains two
      phylogenetically distinct groups, with a total of 10 or more members in C.
      neoformans and at least six members in the sibling species C. gattii. These
      inositol transporter genes are differentially expressed under inositol-inducing
      conditions based on quantitative real-time PCR analyses. Expression of ITR genes
      in a Saccharomyces cerevisiae itr1 itr2 mutant lacking inositol transport can
      complement the slow-growth phenotype of this strain, confirming that ITR genes
      are bona fide inositol transporters. Gene mutagenesis studies reveal that the
      Itr1 and Itr1A transporters are important for myo-inositol stimulation of mating
      and that functional redundancies among the myo-inositol transporters likely
      exist. Deletion of the inositol 1-phosphate synthase gene INO1 in an itr1 or
      itr1a mutant background compromised virulence in a murine inhalation model,
      indicating the importance of inositol sensing and acquisition for fungal
      infectivity. Our study provides a platform for further understanding the roles of
      inositol in fungal physiology and virulence.

PMID- 20689744
TI  - The PB2-E627K mutation attenuates viruses containing the 2009 H1N1 influenza
      pandemic polymerase.
AB  - The swine-origin H1N1 influenza A virus emerged in early 2009 and caused the
      first influenza pandemic in 41 years. The virus has spread efficiently to both
      the Northern and the Southern Hemispheres and has been associated with over
      16,000 deaths. Given the virus's recent zoonotic origin, there is concern that
      the virus could acquire signature mutations associated with the enhanced
      pathogenicity of previous pandemic viruses or H5N1 viruses with pandemic
      potential. We tested the hypothesis that mutations in the polymerase PB2 gene at
      residues 627 and 701 would enhance virulence but found that influenza viruses
      containing these mutations in the context of the pandemic virus polymerase
      complex are attenuated in cell culture and mice.

PMID- 20689745
TI  - Global warming will bring new fungal diseases for mammals.
AB  - Fungi are major pathogens of plants, other fungi, rotifers, insects, and
      amphibians, but relatively few cause disease in mammals. Fungi became important
      human pathogens only in the late 20th century, primarily in hosts with impaired
      immunity as a consequence of medical interventions or HIV infection. The
      relatively high resistance of mammals has been attributed to a combination of a
      complex immune system and endothermy. Mammals maintain high body temperatures
      relative to environmental temperatures, creating a thermally restrictive ambient
      for the majority of fungi. According to this view, protection given by endothermy
      requires a temperature gradient between those of mammals and the environment. We
      hypothesize that global warming will increase the prevalence of fungal diseases
      in mammals by two mechanisms: (i) increasing the geographic range of currently
      pathogenic species and (ii) selecting for adaptive thermotolerance for species
      with significant pathogenic potential but currently not pathogenic by virtue of
      being restricted by mammalian temperatures.

PMID- 20689746
TI  - Regulation of Virulence of Entamoeba histolytica by the URE3-BP Transcription
      Factor.
AB  - It is not understood why only some infections with Entamoeba histolytica result
      in disease. The calcium-regulated transcription factor upstream regulatory
      element 3-binding protein (URE3-BP) was initially identified by virtue of its
      role in regulating the expression of two amebic virulence genes, the Gal/GalNac
      lectin and ferredoxin. Here we tested whether this transcription factor has a
      broader role in regulating virulence. A comparison of in vivo to in vitro
      parasite gene expression demonstrated that 39% of in vivo regulated transcripts
      contained the URE3 motif recognized by URE3-BP, compared to 23% of all promoters
      (P < 0.0001). Amebae induced to express a dominant positive mutant form of URE3
      BP had an increase in an elongated morphology (30% +/- 6% versus 14% +/- 5%; P =
      0.001), a 2-fold competitive advantage at invading the intestinal epithelium (P =
      0.017), and a 3-fold increase in liver abscess size (0.1 +/- 0.1 g versus 0.036
      +/- 0.1 g; P = 0.03). These results support a role for URE3-BP in virulence
      regulation.

PMID- 20689747
TI  - Back to the future: studying cholera pathogenesis using infant rabbits.
AB  - Cholera is a severe diarrheal disease, caused by Vibrio cholerae, for which there
      has been no reproducible, nonsurgical animal model. Here, we report that
      orogastric inoculation of V. cholerae into 3-day-old rabbits pretreated with
      cimetidine led to lethal, watery diarrhea in virtually all rabbits. The
      appearance and chemical composition of the rabbit diarrheal fluid were comparable
      to those of the "rice-water stool" produced by cholera patients. As in humans, V.
      cholerae mutants that do not produce cholera toxin (CT) and toxin-coregulated
      pilus (TCP) did not induce cholera-like disease in rabbits. CT induced extensive
      exocytosis of mucin from intestinal goblet cells, and wild-type V. cholerae was
      predominantly found in close association with mucin. Large aggregates of mucin
      embedded V. cholerae were observed, both attached to the epithelium and floating
      within the diarrheal fluid. These findings suggest that CT-dependent mucin
      secretion significantly influences V. cholerae's association with the host
      intestine and its exit from the intestinal tract. Our model should facilitate
      identification and analyses of factors that may govern V. cholerae infection,
      survival, and transmission, such as mucin. In addition, our results using
      nontoxigenic V. cholerae suggest that infant rabbits will be useful for study of
      the reactogenicity of live attenuated-V. cholerae vaccines.

PMID- 20689748
TI  - Universal vaccines: shifting to one for many.
AB  - Human vaccines, with their exquisite antigenic specificity, have greatly helped
      to eliminate or dramatically abate the incidence of a number of historical and
      current plagues, from smallpox to bacterial meningitis. Nonetheless, as new
      infectious agents emerge and the number of vaccine-preventable diseases
      increases, the practice and benefits of single-pathogen- or disease-targeted
      vaccination may be put at risk by constraints of timely production, formulation
      complexity, and regulatory hurdles. During the last influenza pandemic,
      extraordinary efforts by vaccine producers and health authorities have had little
      or no influence on disease prevention or mitigation. Recent research
      demonstrating the possibility of protecting against all influenza A virus types
      or even phylogenetically distant pathogens with vaccines based on highly
      conserved peptide or saccharide sequences is changing our paradigm. "Universal
      vaccine" strategies could be particularly advantageous to address protection from
      antibiotic-resistant bacteria and fungi for which no vaccine is currently
      available.

PMID- 20689749
TI  - KinD is a checkpoint protein linking spore formation to extracellular-matrix
      production in Bacillus subtilis biofilms.
AB  - Bacillus subtilis cells form multicellular biofilm communities in which
      spatiotemporal regulation of gene expression occurs, leading to differentiation
      of multiple coexisting cell types. These cell types include matrix-producing and
      sporulating cells. Extracellular matrix production and sporulation are linked in
      that a mutant unable to produce matrix is delayed for sporulation. Here, we show
      that the delay in sporulation is not due to a growth advantage of the matrix
      deficient mutant under these conditions. Instead, we show that the link between
      matrix production and sporulation is through the Spo0A signaling pathway. Both
      processes are regulated by the phosphorylated form of the master transcriptional
      regulator Spo0A. When cells have low levels of phosphorylated Spo0A (Spo0A~P),
      matrix genes are expressed; however, at higher levels of Spo0A~P, sporulation
      commences. We have found that Spo0A~P levels are maintained at low levels in the
      matrix-deficient mutant, thereby delaying expression of sporulation-specific
      genes. This is due to the activity of one of the components of the Spo0A
      phosphotransfer network, KinD. A deletion of kinD suppresses the sporulation
      defect of matrix mutants, while its overproduction delays sporulation. Our data
      indicate that KinD displays a dual role as a phosphatase or a kinase and that its
      activity is linked to the presence of extracellular matrix in the biofilms. We
      propose a novel role for KinD in biofilms as a checkpoint protein that regulates
      the onset of sporulation by inhibiting the activity of Spo0A until matrix, or a
      component therein, is sensed.

PMID- 20689750
TI  - Simple sari cloth filtration of water is sustainable and continues to protect
      villagers from cholera in Matlab, Bangladesh.
AB  - A simple method for filtering water to reduce the incidence of cholera was tested
      in a field trial in Matlab, Bangladesh, and proved effective. A follow-up study
      was conducted 5 years later to determine whether the filtration method continued
      to be employed by villagers and its impact on the incidence of cholera. A total
      of 7,233 village women collecting water daily for their households in Bangladesh
      were selected from the same study population of the original field trial for
      interviewing. Analysis of the data showed that 31% of the women used a filter of
      which 60% used sari filters for household water. Results showed that sari
      filtration not only was accepted and sustained by the villagers and benefited
      them, including their neighbors not filtering water, in reducing the incidence of
      cholera, the latter being an unexpected benefit.

PMID- 20689751
TI  - Widespread antisense transcription in Escherichia coli.
AB  - The vast majority of annotated transcripts in bacteria are mRNAs. Here we
      identify ~1,000 antisense transcripts in the model bacterium Escherichia coli. We
      propose that these transcripts are generated by promiscuous transcription
      initiation within genes and that many of them regulate expression of the
      overlapping gene.

PMID- 20689752
TI  - Influenza virus vaccine based on the conserved hemagglutinin stalk domain.
AB  - Although highly effective in the general population when well matched to
      circulating influenza virus strains, current influenza vaccines are limited in
      their utility due to the narrow breadth of protection they provide. The strain
      specificity of vaccines presently in use mirrors the exquisite specificity of the
      neutralizing antibodies that they induce, that is, antibodies which bind to the
      highly variable globular head domain of hemagglutinin (HA). Herein, we describe
      the construction of a novel immunogen comprising the conserved influenza HA stalk
      domain and lacking the globular head. Vaccination of mice with this headless HA
      construct elicited immune sera with broader reactivity than those obtained from
      mice immunized with a full-length HA. Furthermore, the headless HA vaccine
      provided full protection against death and partial protection against disease
      following lethal viral challenge. Our results suggest that the response induced
      by headless HA vaccines is sufficiently potent to warrant their further
      development toward a universal influenza virus vaccine.

PMID- 20689753
TI  - Dynamic distribution of seqa protein across the chromosome of escherichia coli K
      12.
AB  - The bacterial SeqA protein binds to hemi-methylated GATC sequences that arise in
      newly synthesized DNA upon passage of the replication machinery. In Escherichia
      coli K-12, the single replication origin oriC is a well-characterized target for
      SeqA, which binds to multiple hemi-methylated GATC sequences immediately after
      replication has initiated. This sequesters oriC, thereby preventing reinitiation
      of replication. However, the genome-wide DNA binding properties of SeqA are
      unknown, and hence, here, we describe a study of the binding of SeqA across the
      entire Escherichia coli K-12 chromosome, using chromatin immunoprecipitation in
      combination with DNA microarrays. Our data show that SeqA binding correlates with
      the frequency and spacing of GATC sequences across the entire genome. Less SeqA
      is found in highly transcribed regions, as well as in the ter macrodomain. Using
      synchronized cultures, we show that SeqA distribution differs with the cell
      cycle. SeqA remains bound to some targets after replication has ceased, and these
      targets locate to genes encoding factors involved in nucleotide metabolism,
      chromosome replication, and methyl transfer.

PMID- 20689754
TI  - SRC: a century of science brought to the clinic.
AB  - The SRC family kinases are the largest family of nonreceptor tyrosine kinases and
      one of the best-studied targets for cancer therapy. SRC, arguably the oldest
      oncogene, has been implicated in pathways regulating proliferation, angiogenesis,
      invasion and metastasis, and bone metabolism. More recently, researchers have
      proposed that the transforming ability of SRC is linked to its ability to
      activate key signaling molecules in these pathways, rather than through direct
      activity. It has been hypothesized that blocking SRC activation may inhibit these
      pathways, resulting in antitumor activity. However, successfully targeting SRC in
      a clinical setting remains a challenge, and SRC inhibitors have only recently
      begun to move through clinical development. Preclinical studies have identified
      specific molecular "subgroups" and histologies that may be more sensitive to SRC
      inhibition. In addition, other studies have demonstrated synergistic interactions
      between SRC inhibitors and other targeted therapies and cytotoxics. In this
      review, we summarize SRC biology and how it has been applied to the clinical
      development of SRC inhibitors. The status of SRC inhibitors, including dasatinib,
      saracatinib, and bosutinib, which are in phase 1, 2, and 3 trials, is
      highlighted.

PMID- 20689755
TI  - Hypoxic tumor microenvironments reduce collagen I fiber density.
AB  - Although the mechanisms through which hypoxia influences several phenotypic
      characteristics such as angiogenesis, selection for resistance to apoptosis,
      resistance to radiation and chemotherapy, and increased invasion and metastasis
      are well characterized, the relationship between tumor hypoxia and components of
      the extracellular matrix (ECM) is relatively unexplored. The collagen I (Col1)
      fiber matrix of solid tumors is the major structural part of the ECM. Col1 fiber
      density can increase tumor initiation, progression, and metastasis, with cancer
      cell invasion occurring along radially aligned Col1 fibers. Here we have
      investigated the influence of hypoxia on Col1 fiber density in solid breast and
      prostate tumor models. Second harmonic generation (SHG) microscopy was used to
      detect differences in Col1 fiber density and volume between hypoxic and normoxic
      tumor regions. Hypoxic regions were detected by fluorescence microscopy, using
      tumors derived from human breast and prostate cancer cell lines stably expressing
      enhanced green fluorescent protein (EGFP) under transcriptional control of the
      hypoxia response element. In-house fiber analysis software was used to
      quantitatively analyze Col1 fiber density and volume from the SHG microscopy
      images. Normoxic tumor regions exhibited a dense mesh of Col1 fibers. In
      contrast, fewer and structurally altered Col1 fibers were detected in hypoxic
      EGFP-expressing tumor regions. Microarray gene expression analyses identified
      increased expression of lysyl oxidase and reduced expression of some matrix
      metalloproteases in hypoxic compared with normoxic cancer cells. These results
      suggest that hypoxia mediates Col1 fiber restructuring in tumors, which may
      impact delivery of macromolecular agents as well as dissemination of cells.

PMID- 20689756
TI  - Effect of eicosapentaenoic acid on E-type prostaglandin synthesis and EP4
      receptor signaling in human colorectal cancer cells.
AB  - The omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA), in the free
      fatty acid (FFA) form, has been demonstrated to reduce adenoma number and size in
      patients with familial adenomatous polyposis. However, the mechanistic basis of
      the antineoplastic activity of EPA in the colorectum remains unclear. We tested
      the hypothesis that EPA-FFA negatively modulates synthesis of and signaling by
      prostaglandin (PG) E(2) in human colorectal cancer (CRC) cells. EPA-FFA induced
      apoptosis of cyclooxygenase (COX)-2-positive human HCA-7 CRC cells in vitro. EPA
      FFA in cell culture medium was incorporated rapidly into phospholipid membranes
      of HCA-7 human CRC cells and acted as a substrate for COX-2, leading to reduced
      synthesis of PGE(2) and generation of PGE(3). Alone, PGE(3) bound and activated
      the PGE(2) EP4 receptor but with reduced affinity and efficacy compared with its
      "natural" ligand PGE(2). However, in the presence of PGE(2), PGE(3) acted as an
      antagonist of EP4 receptor-dependent 3',5' cyclic adenosine monophosphate
      induction in naturally EP4 receptor-positive LoVo human CRC cells and of
      resistance to apoptosis in HT-29-EP4 human CRC cells overexpressing the EP4
      receptor. We conclude that EPA-FFA drives a COX-2-dependent "PGE(2)-to-PGE(3)
      switch" in human CRC cells and that PGE(3) acts as a partial agonist at the
      PGE(2) EP4 receptor.

PMID- 20689757
TI  - MDR1 and ERCC1 expression predict outcome of patients with locally advanced
      bladder cancer receiving adjuvant chemotherapy.
AB  - PURPOSE: The role of adjuvant chemotherapy in patients with locally advanced
      bladder cancer still remains to be defined. We hypothesized that assessing the
      gene expression of the chemotherapy response modifiers multidrug resistance gene
      1 (MDR1) and excision repair cross-complementing 1 (ERCC1) may help identify the
      group of patients benefiting from cisplatin-based adjuvant chemotherapy.
      EXPERIMENTAL DESIGN: Formalin-fixed paraffin-embedded tumor samples from 108
      patients with locally advanced bladder cancer, who had been enrolled in AUO
      AB05/95, a phase 3 trial randomizing a maximum of three courses of adjuvant
      cisplatin and methotrexate (CM) versus methotrexate, vinblastine, epirubicin, and
      cisplatin (M-VEC), were included in the study. Tumor cells were retrieved by
      laser-captured microdissection and analyzed for MDR1 and ERCC1 expression using a
      quantitative real-time reverse transcription-polymerase chain reaction assay.
      Gene expression levels were correlated with clinical outcomes by multivariate Cox
      proportional hazards regression analysis. RESULTS: Expressions of MDR1 and ERCC1
      were independently associated with overall progression-free survival (P = .001,
      relative risk = 2.9 and P = .01, relative risk = 2.24, respectively). The
      correlation of high MDR1 expression with inferior outcome was stronger in
      patients receiving M-VEC, whereas ERCC1 analysis performed equally in the CM and
      M-VEC groups. CONCLUSIONS: High MDR1 and ERCC1 gene expressions are associated
      with inferior outcome after cisplatin-based adjuvant chemotherapy for locally
      advanced bladder cancer. Prospective studies are warranted to define a role for
      MDR1 and ERCC1 analysis in individualizing multimodality treatment in locally
      advanced bladder cancer.

PMID- 20689758
TI  - Pharmacodynamic characterization of the efficacy signals due to selective BRAF
      inhibition with PLX4032 in malignant melanoma.
AB  - PURPOSE: About 65% to 70% of melanomas harbor a mutation in v-raf murine sarcoma
      viral oncogene homolog B1 (BRAF) that causes the steady-state activation of
      extracellular signal-regulated kinase (ERK). We sought to investigate the
      efficacy of PLX4032 (BRAF inhibitor) to identify patterns/predictors of
      response/resistance and to study the effects of BRAF in melanoma. EXPERIMENTAL
      DESIGN: Well-characterized melanoma cell lines, including several with acquired
      drug resistance, were exposed to PLX4032. Growth inhibition, phosphosignaling,
      cell cycle, apoptosis, and gene expression analyses were performed before and
      after exposure to drug. RESULTS: Using a growth-adjusted inhibitory concentration
      of 50% cutoff of 1 microM, 13 of 35 cell lines were sensitive to PLX4032, 16
      resistant, and 6 intermediate (37%, 46%, and 17% respectively). PLX4032 caused
      growth inhibition, G(0)/G(1) arrest, and restored apoptosis in the sensitive cell
      lines. A BRAF mutation predicted for but did not guarantee a response, whereas a
      neuroblastoma RAS viral oncogene homolog mutation or wild-type BRAF conferred
      resistance. Cells with concurrent BRAF mutations and melanocortin 1 receptor germ
      line variants and/or a more differentiated melanocyte genotype had a preferential
      response. Acquired PLX4032 resistance reestablishes ERK signaling, promotes a
      nonmelanocytic genotype, and is associated with an increase in the gene
      expression of certain metallothioneins and mediators of angiogenesis.
      CONCLUSIONS: PLX4032 has robust activity in BRAF mutated melanoma. The
      preclinical use of this molecule identifies criteria for its proper clinical
      application, describes patterns of and reasons for response/resistance, and
      affords insight into the role of a BRAF mutation in melanoma.

PMID- 20689759
TI  - Ron receptor tyrosine kinase activation confers resistance to tamoxifen in breast
      cancer cell lines.
AB  - Although tamoxifen treatment is associated with improved survival in patients
      with estrogen receptor (ER)-positive breast tumors, resistance remains an
      important clinical obstacle. Signaling through growth factor signaling pathways,
      in particular through receptor tyrosine kinases, has been demonstrated to confer
      tamoxifen resistance in an estradiol-independent manner. The Ron receptor
      tyrosine kinase, a member of the c-Met family of receptors, is expressed in a
      number of human epithelial tumors, and elevated expression of Ron is associated
      with poor prognosis in women with breast cancer. In this report, we evaluated the
      role of Ron receptor activation in conferring resistance to tamoxifen in human
      and murine breast cancer cell lines. Activation of Ron by its ligand, hepatocyte
      growth factor-like protein (HGFL) was associated with partial rescue from
      tamoxifen-induced growth inhibition in Ron-expressing cell lines. Western
      analysis revealed that treatment of the T47D human breast cancer cell line with
      tamoxifen and HGFL was associated with increased phosphorylation of mitogen
      activated protein kinase (MAPK) 1/2 and phosphorylation of serine residue 118 of
      ER. Expression of ER-dependent genes was increased in cells treated with
      tamoxifen and HGFL by quantitative reverse transcription-polymerase chain
      reaction. All of these effects were inhibited by treatment with either a Ron
      neutralizing antibody or a MEK1 inhibitor, suggesting the specificity of the
      effect to Ron, and the involvement of the MAPK 1/2 signaling pathway. In summary,
      these results illustrate a novel connection between the Ron receptor tyrosine
      kinase and an important mechanism of tamoxifen resistance in breast cancer.

PMID- 20689760
TI  - Glutamate receptor GRIA3--target of CUX1 and mediator of tumor progression in
      pancreatic cancer.
AB  - Previously, we identified the transcription factor CUX1 as an important modulator
      of invasion and resistance to apoptosis. Expression profiles suggested that CUX1
      regulates a complex transcriptional program mediating tumor progression. We aimed
      to identify functionally relevant targets of CUX1 by using RNA interference
      (RNAi)-based loss-of-function screens. Therefore, we generated an RNAi library
      containing putative transcriptional targets of CUX1 identified by microarrays and
      performed cell viability screens. Using this approach, several CUX1 targets with
      effect on tumor cell viability were identified, including the glutamate receptor
      GRIA3, which was validated in detail for its effects on proliferation, apoptosis,
      and cell migration using RNAi knock-down and overexpression strategies in vitro,
      as well as xenograft models in vivo. The expression of GRIA3 was evaluated in
      human pancreatic cancer tissues. We found that knock-down of GRIA3 significantly
      reduced proliferation and migration and enhanced apoptosis. In contrast,
      overexpression of GRIA3 significantly reduced apoptosis and enhanced both
      proliferation and tumor cell migration. GRIA3 could be confirmed as a downstream
      effector of CUX1 and was expressed in pancreatic cancer tissues. In vivo, GRIA3
      significantly enhanced the growth of subcutaneous xenografts. Inhibitors of
      glutamate receptors such as GYKI52466 and SYM2206 significantly decreased
      survival of pancreatic cancer cells, suggesting the presence of glutamate
      signaling in pancreatic cancer. In conclusion, GRIA3 plays a role as a mediator
      of tumor progression in pancreatic cancer downstream CUX1. To our knowledge, this
      is the first report to identify a glutamate receptor as a modulator of tumor
      progression in a solid cancer outside the brain.

PMID- 20689761
TI  - Replication timing aberrations and aneuploidy in peripheral blood lymphocytes of
      breast cancer patients.
AB  - BACKGROUND: Peripheral blood lymphocytes of patients with hematological
      malignancies or solid tumors, such as renal cell carcinoma or prostate cancer,
      display epigenetic aberrations (loss of synchronous replication of allelic
      counterparts) and genetic changes (aneuploidy) characteristic of the cancerous
      phenotype. This study sought to determine whether such alterations could
      differentiate breast cancer patients from cancer-free subjects. METHODS: The HER2
      locus-an oncogene assigned to chromosome 17 whose amplification is associated
      with breast cancer (BCA)-and the pericentromeric satellite sequence of chromosome
      17 (CEN17) were used for replication timing assessments. Aneuploidy was monitored
      by enumerating the copy numbers of chromosome 17. Replication timing and
      aneuploidy were detected cytogenetically using fluorescence in situ hybridization
      technology applied to phytohemagglutinin-stimulated lymphocytes of 20 women with
      BCA and 10 control subjects. RESULTS: We showed that both the HER2 and CEN17 loci
      in the stimulated BCA lymphocytes altered their characteristic pattern of
      synchronous replication and exhibited asynchronicity. In addition, there was an
      increase in chromosome 17 aneuploidy. The frequency of cells displaying
      asynchronous replication in the patients' samples was significantly higher (P <
      10(-12) for HER2 and P < 10(-6) for CEN17) than the corresponding values in the
      control samples. Similarly, aneuploidy in patients' cells was significantly
      higher (P < 10(-9)) than that in the controls. CONCLUSIONS: The HER2 and CEN17
      aberrant replication differentiated clearly between BCA patients and control
      subjects. Thus, monitoring the replication of these genes offers potential blood
      markers for the detection and monitoring of breast cancer.

PMID- 20689762
TI  - Differential Antitumor Effects of IgG and IgM Monoclonal Antibodies and Their
      Synthetic Complementarity-Determining Regions Directed to New Targets of B16F10
      Nex2 Melanoma Cells.
AB  - Malignant melanoma has increased incidence worldwide and causes most skin cancer
      related deaths. A few cell surface antigens that can be targets of antitumor
      immunotherapy have been characterized in melanoma. This is an expanding field
      because of the ineffectiveness of conventional cancer therapy for the metastatic
      form of melanoma. In the present work, antimelanoma monoclonal antibodies (mAbs)
      were raised against B16F10 cells (subclone Nex4, grown in murine serum), with
      novel specificities and antitumor effects in vitro and in vivo. MAb A4 (IgG2ak)
      recognizes a surface antigen on B16F10-Nex2 cells identified as protocadherin
      beta(13). It is cytotoxic in vitro and in vivo to B16F10-Nex2 cells as well as in
      vitro to human melanoma cell lines. MAb A4M (IgM) strongly reacted with nuclei of
      permeabilized murine tumor cells, recognizing histone 1. Although it is not
      cytotoxic in vitro, similarly with mAb A4, mAb A4M significantly reduced the
      number of lung nodules in mice challenged intravenously with B16F10-Nex2 cells.
      The V(H) CDR3 peptide from mAb A4 and V(L) CDR1 and CDR2 from mAb A4M showed
      significant cytotoxic activities in vitro, leading tumor cells to apoptosis. A
      cyclic peptide representing A4 CDR H3 competed with mAb A4 for binding to
      melanoma cells. MAb A4M CDRs L1 and L2 in addition to the antitumor effect also
      inhibited angiogenesis of human umbilical vein endothelial cells in vitro. As
      shown in the present work, mAbs A4 and A4M and selected CDR peptides are strong
      candidates to be developed as drugs for antitumor therapy for invasive melanoma.

PMID- 20689763
TI  - Artemin Reduces Sensitivity to Doxorubicin and Paclitaxel in Endometrial
      Carcinoma Cells through Specific Regulation of CD24.
AB  - We have previously reported that artemin (ARTN) stimulates the oncogenicity and
      invasiveness of endometrial carcinoma cells. Herein, we demonstrate that ARTN
      modulates the sensitivity of endometrial carcinoma cells to agents used to treat
      late-stage endometrial carcinoma. Forced expression of ARTN in endometrial
      carcinoma cells decreased sensitivity to doxorubicin and paclitaxel. Accordingly,
      depletion of ARTN by small interfering RNA or functional inhibition of ARTN with
      antibodies significantly increased sensitivity of endometrial carcinoma cells to
      doxorubicin and paclitaxel. Forced expression of ARTN in endometrial carcinoma
      cells abrogated doxorubicin-induced G(2)-M arrest and paclitaxel-induced
      apoptosis. ARTN increased CD24 expression in endometrial carcinoma cells by
      transcriptional up-regulation, and CD24 was partially correlated to ARTN
      expression in endometrial carcinoma. Forced expression of CD24 in endometrial
      carcinoma cells stimulated cell proliferation and oncogenicity, enhanced cell
      invasion, and decreased sensitivity to doxorubicin and paclitaxel. Depletion of
      CD24 in endometrial carcinoma cells abrogated ARTN-stimulated resistance to
      doxorubicin and paclitaxel. ARTN-stimulated resistance to doxorubicin and
      paclitaxel in endometrial carcinoma cells is therefore mediated by the specific
      regulation of CD24. Functional inhibition of ARTN may therefore be considered as
      an adjuvant therapeutic approach to improve the response of endometrial carcinoma
      to specific chemotherapeutic agents.

PMID- 20689764
TI  - Effect of ovarian cancer ascites on cell migration and gene expression in an
      epithelial ovarian cancer in vitro model.
AB  - A third of patients with epithelial ovarian cancer (EOC) present ascites. The
      cellular fraction of ascites often consists of EOC cells, lymphocytes, and
      mesothelial cells, whereas the acellular fraction contains cytokines and
      angiogenic factors. Clinically, the presence of ascites correlates with
      intraperitoneal and retroperitoneal tumor spread. We have used OV-90, a
      tumorigenic EOC cell line derived from the malignant ascites of a chemonaive
      ovarian cancer patient, as a model to assess the effect of ascites on migration
      potential using an in vitro wound-healing assay. A recent report of an invasion
      assay described the effect of ascites on the invasion potential of the OV-90 cell
      line. Ascites sampled from 31 ovarian cancer patients were tested and compared
      with either 5% fetal bovine serum or no serum for their nonstimulatory or
      stimulatory effect on the migration potential of the OV-90 cell line. A
      supervised analysis of data generated by the Affymetrix HG-U133A GeneChip
      identified differentially expressed genes from OV-90 cells exposed to ascites
      that had either a nonstimulatory or a stimulatory effect on migration. Ten genes
      (IRS2, CTSD, NRAS, MLXIP, HMGCR, LAMP1, ETS2, NID1, SMARCD1, and CD44) were
      upregulated in OV-90 cells exposed to ascites, allowing a nonstimulatory effect
      on cell migration. These findings were validated by quantitative polymerase chain
      reaction. In addition, the gene expression of IRS2 and MLXIP each correlated with
      prognosis when their expression was assessed in an independent set of primary
      cultures established from ovarian ascites. This study revealed novel candidates
      that may play a role in ovarian cancer cell migration.

PMID- 20689765
TI  - High SEPT9_v1 Expression Is Associated with Poor Clinical Outcomes in Head and
      Neck Squamous Cell Carcinoma.
AB  - The purpose of this work was to determine SEPT9_v1 expression levels in head and
      neck squamous cell carcinoma (HNSCC) and to analyze whether SEPT9_v1 expression
      is relevant to clinical outcomes. Recently, the SEPT9 isoform SEPT9_v1 has been
      implicated in oncogenesis, and methylation of the SEPT9 promoter region was
      reported in HNSCC. These findings led us to hypothesize that SEPT9_v1 could be
      differently expressed in HNSCC. To determine whether SEPT9_v1 is expressed in
      HNSCC, tissue microarray immunohistochemical analysis was performed using a
      SEPT9_v1-specific antibody. Tissue microarrays stained with a polyclonal SEPT9_v1
      specific antibody was used to determine protein expression levels in HNSCC tissue
      samples, some with known clinical outcomes. This analysis showed that SEPT9_v1 is
      in fact highly expressed in HNSCC compared with normal epithelium, and high
      expression levels directly correlated with poor clinical outcomes. Specifically,
      a high SEPT9_v1 expression was associated with decreased disease-specific
      survival (P = .012), time to indication of surgery at primary site (P = .008),
      response to induction chemotherapy (P = .0002), and response to chemotherapy (P =
      .02), as well as advanced tumor stage (P = .012) and N stage (P = .0014). The
      expression of SEPT9_v1 was also strongly correlated with smoking status (P =
      .00094). SEPT9_v1 is highly expressed in HNSCC, and a high expression of SEPT9_v1
      is associated with poor clinical outcomes. These data indicate that SEPT9_v1
      warrants additional investigation as a potential biomarker for HNSCC.

PMID- 20689766
TI  - Comparison of the side populations in pretreatment and postrelapse neuroblastoma
      cell lines.
AB  - Cancer stem-like cells have been identified in both primary tumors and in cell
      lines and seem to have a high degree of inherent resistance to traditional
      chemotherapeutic agents. Relapsed cancers including neuroblastoma are generally
      chemotherapy-resistant and carry a very poor prognosis. We investigated the side
      populations of three pairs of neuroblastoma cell lines derived from single
      patients at the time of their initial presentation and then at relapse after
      multimodality therapy. We found that the size of the side populations in the
      relapsed cell lines was significantly increased compared with its paired
      pretreatment cell line. In addition, these side population cells showed increased
      proliferation and were significantly more efficient at forming colonies in soft
      agar than their prerelapse pair. Gene expression analysis of the stem cell genes
      NANOG and POU5F1 (Oct3/4) showed increased expression in the unsorted relapsed
      cell lines compared with pretreatment lines as well as in the side populations of
      the relapsed versus prerelapse cell line pairs. The increased size, proliferative
      ability, and colony-forming efficiency of the side populations of the postrelapse
      cell lines demonstrated in this study suggest that a population of stemlike cells
      is not being efficiently targeted by conventional therapy and implies that
      strategies to specifically target the stem cell fraction of neuroblastomas are
      needed to improve outcomes in this devastating childhood disease.

PMID- 20689767
TI  - Monitoring the Effect of Docetaxel Treatment in MCF7 Xenografts Using Multimodal
      In Vivo and Ex Vivo Magnetic Resonance Methods, Histopathology, and Gene
      Expression.
AB  - The purpose of this study was to evaluate the sensitivity of dynamic contrast
      enhanced magnetic resonance imaging (DCE-MRI), diffusion-weighted (DW)-MRI, in
      vivo MR spectroscopy (MRS), and ex vivo high-resolution magic angle spinning (HR
      MAS) MRS for the detection of early treatment effects after docetaxel
      administration. Docetaxel is an antitumor agent that leads to mitotic arrest,
      apoptosis, and mitotic catastrophe cell death. Gene expression analysis was
      performed to detect altered regulation in gene expression pathways related to
      docetaxel treatment effects. Histopathology was used as a measure of alterations
      in apoptosis and proliferation due to docetaxel. Experiments were performed using
      MCF7 mouse xenografts, randomized into a docetaxel (30 mg/kg) treatment group and
      a control group given saline. MRI/MRS was performed 1 day before treatment and 1,
      3, and 6 days after treatment. Parametric images of the extracellular
      extravascular volume fraction (v(e)) transfer constant (K(trans)) and the
      apparent diffusion coefficient (ADC) were calculated from the DCE-MRI and DW-MRI
      data. Biopsies were analyzed by HR MAS MRS, and histopathology and gene
      expression profiles were determined (Illumina). A significant increase in the ADC
      3 and 6 days after treatment and a significant decrease in total choline and a
      higher v(e) were found in treated tumors 6 days after treatment. No significant
      difference was found in the K(trans) between the two groups. Our results show
      that docetaxel induces apoptosis and decreases proliferation in MCF7 xenografts.
      Further, these phenomena can be monitored by in vivo MRS, DW-MRI, and gene
      expression.

PMID- 20689768
TI  - Anti-Angiogenic/Vascular Effects of the mTOR Inhibitor Everolimus Are Not
      Detectable by FDG/FLT-PET.
AB  - Noninvasive functional imaging of tumors can provide valuable early-response
      biomarkers, in particular, for targeted chemotherapy. Using various experimental
      tumor models, we have investigated the ability of positron emission tomography
      (PET) measurements of 2-deoxy-2-[(18)F]fluoro-glucose (FDG) and 3'-deoxy-3'
      [(18)F]fluorothymidine (FLT) to detect response to the allosteric mammalian
      target of rapamycin (mTOR) inhibitor everolimus. Tumor models were declared
      sensitive (murine melanoma B16/BL6 and human lung H596) or relatively insensitive
      (human colon HCT116 and cervical KB31), according to the IC(50) values
      (concentration inhibiting cell growth by 50%) for inhibition of proliferation in
      vitro (<10 nM and >1 microM, respectively). Everolimus strongly inhibited growth
      of the sensitive models in vivo but also significantly inhibited growth of the
      insensitive models, an effect attributable to its known anti-angiogenic/vascular
      properties. However, although tumor FDG and FLT uptake was significantly reduced
      in the sensitive models, it was not affected in the insensitive models,
      suggesting that endothelial-directed effects could not be detected by these PET
      tracers. Consistent with this hypothesis, in a well-vascularized orthotopic rat
      mammary tumor model, other antiangiogenic agents also failed to affect FDG
      uptake, despite inhibiting tumor growth. In contrast, the cytotoxic patupilone, a
      microtubule stabilizer, blocked tumor growth, and markedly reduced FDG uptake.
      These results suggest that FDG/FLT-PET may not be a suitable method for early
      markers of response to antiangiogenic agents and mTOR inhibitors in which anti
      angiogenic/vascular effects predominate because the method could provide false
      negative responses. These conclusions warrant clinical testing.

PMID- 20689769
TI  - A Polymorphic Variant of AFAP-110 Enhances cSrc Activity.
AB  - Enhanced expression and activity of cSrc are associated with ovarian cancer
      progression. Generally, cSrc does not contain activating mutations; rather, its
      activity is increased in response to signals that affect a conformational change
      that releases its autoinhibition. In this report, we analyzed ovarian cancer
      tissues for the expression of a cSrc-activating protein, AFAP-110. AFAP-110
      activates cSrc through a direct interaction that releases it from its
      autoinhibited conformation. Immunohistochemical analysis revealed a concomitant
      increase of AFAP-110 and cSrc in ovarian cancer tissues. An analysis of the AFAP
      110 coding sequence revealed the presence of a nonsynonymous, single-nucleotide
      polymorphism that resulted in a change of Ser403 to Cys403. In cells that express
      enhanced levels of cSrc, AFAP-110(403C) directed the activation of cSrc and the
      formation of podosomes independently of input signals, in contrast to wild-type
      AFAP-110. We therefore propose that, under conditions of cSrc overexpression, the
      polymorphic variant of AFAP-110 promotes cSrc activation. Further, these data
      indicate amechanismby which an inherited genetic variation could influence
      ovarian cancer progression and could be used to predict the response to targeted
      therapy.

PMID- 20689770
TI  - The glycobiome of the rumen bacterium Butyrivibrio proteoclasticus B316(T)
      highlights adaptation to a polysaccharide-rich environment.
AB  - Determining the role of rumen microbes and their enzymes in plant polysaccharide
      breakdown is fundamental to understanding digestion and maximising productivity
      in ruminant animals. Butyrivibrio proteoclasticus B316(T) is a gram-positive,
      butyrate-forming rumen bacterium with a key role in plant polysaccharide
      degradation. The 4.4 Mb genome consists of 4 replicons; a chromosome, a chromid
      and two megaplasmids. The chromid is the smallest reported for all bacteria, and
      the first identified from the phylum Firmicutes. B316 devotes a large proportion
      of its genome to the breakdown and reassembly of complex polysaccharides and has
      a highly developed glycobiome when compared to other sequenced bacteria. The
      secretion of a range of polysaccharide-degrading enzymes which initiate the
      breakdown of pectin, starch and xylan, a subtilisin family protease active
      against plant proteins, and diverse intracellular enzymes to break down
      oligosaccharides constitute the degradative capability of this organism. A
      prominent feature of the genome is the presence of multiple gene clusters
      predicted to be involved in polysaccharide biosynthesis. Metabolic reconstruction
      reveals the absence of an identifiable gene for enolase, a conserved enzyme of
      the glycolytic pathway. To our knowledge this is the first report of an organism
      lacking an enolase. Our analysis of the B316 genome shows how one organism can
      contribute to the multi-organism complex that rapidly breaks down plant material
      in the rumen. It can be concluded that B316, and similar organisms with broad
      polysaccharide-degrading capability, are well suited to being early colonizers
      and degraders of plant polysaccharides in the rumen environment.

PMID- 20689772
TI  - Gesundes Kinzigtal Integrated Care: improving population health by a shared
      health gain approach and a shared savings contract.
AB  - INTRODUCTION: Integrated care solutions need supportive financial incentives. In
      this paper, we describe the financial architecture and operative details of the
      integrated pilot Gesundes Kinzigtal. DESCRIPTION OF INTEGRATED CARE CASE: Located
      in Southwest Germany, Gesundes Kinzigtal is one of the few population-based
      integrated care approaches in Germany, organising care across all health service
      sectors and indications. The system serving around half of the population of the
      region is run by a regional health management company (Gesundes Kinzigtal GmbH)
      in cooperation with the physicians' network in the region (MQNK), a German health
      care management company with a background in medical sociology and health
      economics (OptiMedis AG) and with two statutory health insurers (among them is
      the biggest health insurer in Southwest Germany: AOK Baden-Wurttemberg).
      DISCUSSION AND (PRELIMINARY) CONCLUSION: The shared savings contract between
      Gesundes Kinzigtal GmbH and the two health insurers, providing financial
      incentives for managers and health care providers to realize a substantial
      efficiency gain, could be an appropriate contractual base of Gesundes Kinzigtal's
      population health gain approach. This approach is based on the assumption that a
      more effective trans-sector organization of Germany's health care system and
      increased investments in well-designed preventive programmes will lead to a
      reduction in morbidity, and in particular to a reduced incidence and prevalence
      of chronic diseases. This, in turn, is to lead to a comparative reduction in
      health care cost. Although the comparative cost in the Kinzigtal region has been
      reduced from the onset of Gesundes Kinzigtal Integrated Care, only future
      research will have to demonstrate whether-and to what extent-cost reduction may
      be attributed to a real population health gain.

PMID- 20689771
TI  - Trichomonas transmembrane cyclases result from massive gene duplication and
      concomitant development of pseudogenes.
AB  - BACKGROUND: Trichomonas vaginalis has an unusually large genome (approximately
      160 Mb) encoding approximately 60,000 proteins. With the goal of beginning to
      understand why some Trichomonas genes are present in so many copies, we
      characterized here a family of approximately 123 Trichomonas genes that encode
      transmembrane adenylyl cyclases (TMACs). METHODOLOGY/PRINCIPAL FINDINGS: The
      large family of TMACs genes is the result of recent duplications of a small set
      of ancestral genes that appear to be unique to trichomonads. Duplicated TMAC
      genes are not closely associated with repetitive elements, and duplications of
      flanking sequences are rare. However, there is evidence for TMAC gene
      replacements by homologous recombination. A high percentage of TMAC genes
      (approximately 46%) are pseudogenes, as they contain stop codons and/or frame
      shifts, or the genes are truncated. Numerous stop codons present in the genome
      project G3 strain are not present in orthologous genes of two other Trichomonas
      strains (S1 and B7RC2). Each TMAC is composed of a series of N-terminal
      transmembrane helices and a single C-terminal cyclase domain that has adenylyl
      cyclase activity. Multiple TMAC genes are transcribed by Trichomonas cloned by
      limiting dilution. CONCLUSIONS/SIGNIFICANCE: We conclude that one reason for the
      unusually large genome of Trichomonas is the presence of unstable families of
      genes such as those encoding TMACs that are undergoing massive gene duplication
      and concomitant development of pseudogenes.

PMID- 20689773
TI  - Novel index for micromixing characterization and comparative analysis.
AB  - The most basic micromixer is a T- or Y-mixer, where two confluent streams mix due
      to transverse diffusion. To enhance micromixing, various modifications of T
      mixers are reported such as heterogeneously charged walls, grooves on the channel
      base, geometric variations by introducing physical constrictions, etc. The
      performance of these reported designs is evaluated against the T-mixer in terms
      of the deviation from perfectly mixed state and mixing length (device length
      required to achieve perfect mixing). Although many studies have noticed the
      reduced flow rates for improved mixer designs, the residence time is not taken
      into consideration for micromixing performance evaluation. In this work, we
      propose a novel index, based on residence time, for micromixing characterization
      and comparative analysis. For any given mixer, the proposed index identifies the
      nondiffusive mixing enhancement with respect to the T-mixer. Various micromixers
      are evaluated using the proposed index to demonstrate the usefulness of the
      index. It is also shown that physical constriction mixer types are equivalent to
      T-mixers. The proposed index is found to be insightful and could be used as a
      benchmark for comparing different mixing strategies.

PMID- 20689774
TI  - Living with severe physical impairment, Duchenne's muscular dystrophy and home
      mechanical ventilation.
AB  - AIM: To study life-experiences of people living with Duchenne's muscular
      dystrophy (DMD), home mechanical ventilation (HMV) and physical impairment.
      BACKGROUND: Since the introduction of invasive HMV in the late 1980s people with
      DMD in Denmark live longer and have the experience of adulthood and a high degree
      of physical dependency. METHOD: Nineteen patients with DMD and invasive HMV were
      interviewed in 2007. The interviews were recorded, transcribed verbatim and
      analysed according to a method inspired by Ricoeur's theory of interpretation.
      FINDINGS: HMV not only extended the participants lifespan, it also gave them the
      capacity to live an active life. They were totally dependent in everyday living,
      but in spite of this, they did not see themselves as physically impaired. They
      realised that there were activities that were physically impossible, but they
      considered themselves to be just the same person they had always been. This
      dependency was described as "independent dependency". CONCLUSION: The lived
      experience of physical impairment is found to be "independent dependency" in an
      active life. To solve problems with loneliness, society needs to work with
      prejudice and misunderstanding and for better physical accessibility to enable
      full participation.

PMID- 20689775
TI  - Some thoughts about the literature review in grounded theory studies.

PMID- 20689776
TI  - Effect of travoprost on 24-hour intraocular pressure in normal tension glaucoma.
AB  - PURPOSE: The effect of travoprost 0.004% on 24-hour intraocular pressure (IOP)
      was examined in patients with normal tension glaucoma (NTG). SUBJECTS AND
      METHODS: This study included 17 patients with newly diagnosed unilateral NTG. IOP
      was measured at three-hour intervals over 24 hours by Goldman applanation
      tonometer in patients taking topical travoprost 0.004% and was compared
      retrospectively with 24-hour IOP data in untreated eyes. RESULTS: IOP values were
      significantly reduced at individual time points after treatment (P < 0.01). Mean
      24-hour IOP, maximum 24-hour IOP, minimum 24-hour IOP, and 24-hour IOP
      fluctuations at baseline (mean +/- SD) were 12.9 +/- 2.2 mmHg, 15.4 +/- 2.7 mmHg,
      10.5 +/- 2.2 mmHg, and 4.9 +/- 1.2 mmHg, respectively, and were significantly
      reduced to 10.3 +/- 2.0 mmHg, 12.4 +/- 2.5 mmHg, 8.5 +/- 1.9 mmHg (all P <
      0.001), and 3.9 +/- 1.5 mmHg (P < 0.05), respectively, after treatment. The rate
      of IOP reduction greater than 20% was 58.8% (10 eyes) for maximum 24-hour IOP and
      53.0% (nine eyes) for mean 24-hour IOP. CONCLUSION: Travoprost reduced IOP
      throughout the 24-hour study period, with over half of the eyes examined showing
      IOP reduction exceeding 20%.

PMID- 20689777
TI  - In vivo comparative study of ocular vasodilation, a relative indicator of
      hyperemia, in guinea pigs following treatment with bimatoprost ophthalmic
      solutions 0.01% and 0.03%.
AB  - OBJECTIVE: The objective of this in vivo study was to compare the incidence of
      vasodilation in guinea pigs following topical administration of bimatoprost
      ophthalmic solutions 0.01% and 0.03%. METHODS: The study comprised 20 guinea pigs
      assigned to 2 treatment groups (10 per treatment group) to receive either
      bimatoprost 0.01% or bimatoprost 0.03%. Animals were hand-held under 2.75 x
      magnification to score ocular vasodilation (a measure of hyperemia), using a
      scoring system developed at Alcon Research, Ltd. Following baseline ocular
      scoring, each animal received a 30 muL dose to the left eye of either bimatoprost
      0.01% (3 mug) or bimatoprost 0.03% (9 mug). Vasodilation was again scored at 1,
      2, 3, 4, 5 and 6 hours after dosing. Incidence of vasodilation was calculated as
      the percent of total eyes in each 2-hour time interval with scores >/=2. RESULTS:
      The incidence of vasodilation was higher in the bimatoprost 0.01% treatment group
      (range, 45.0% to 60.0%) than the bimatoprost 0.03% treatment group (range, 30.0%
      to 52.2%) at all post-dosing time points. CONCLUSION: The 2 bimatoprost
      formulations elicited ocular vasodilation of long duration (>6 hours) in the
      guinea pig model, with the bimatoprost 0.01% treatment group showing a higher
      incidence of ocular vasodilation than the bimatoprost 0.03% treatment group.
      Further clinical studies would be needed to determine whether the higher
      incidence of vasodilation may also be attributed to the increased BAK
      concentration in the bimatoprost 0.01% formulation.

PMID- 20689778
TI  - Free radicals in the aqueous humor of patients with glaucoma.
AB  - PURPOSE: To clarify the presence of oxidative stress in glaucoma and discuss
      whether free radicals contribute to neovascular glaucoma (NVG) and non-NVG.
      METHODS: Two patient groups were formed: the NVG group (n = 10) and the non-NVG
      group (n = 17). Free radicals in aqueous humor were detected by measuring the
      electron spin resonance (ESR). To identify free radical species, either
      superoxide dismutase (SOD) or catalase was added to the aqueous humor and
      compared with aqueous humor in which SOD or catalase was not added. RESULTS: In
      the NVG group, free radical waveforms were detected that differed from ascorbate
      free radical (AFR) in all cases. Under SOD was added, the characteristic
      waveforms disappeared and the AFR of a specific waveform appeared. After catalase
      was added, the waveforms were unchanged. In the non-NVG group, the AFR of
      specific waveforms were detected in all cases. In 4 cases, the waveforms detected
      the presence of a trace of superoxide. CONCLUSIONS: In the NVG group, superoxides
      were detected, suggesting that superoxide scavenging activity was decreased
      markedly. L-ascorbic acid likely has an antioxidative function in the non-NVG
      group, suggesting that the aqueous humor in the NVG group was under higher
      oxidative stress compared with the non-NVG group.

PMID- 20689779
TI  - Blindness and visual impairment in retinitis pigmentosa: a Cameroonian hospital
      based study.
AB  - AIM: We performed a retrospective, analytical study in February 2010 on all
      retinitis pigmentosa cases seen during ophthalmologic consultation at the Gyneco
      Obstetrics and Pediatric Hospital of Yaounde between March 2002 and December 2009
      (82 months). The aim of this research was to determine the significance of
      blindness and visual impairment associated with retinitis pigmentosa in Cameroon.
      RESULTS: Forty cases were reported, corresponding to a hospital prevalence of
      1.6/1000 (21 men and 19 women). The average age of the patients was 43.3 +/- 18
      years, ranging between 6 and 74 years. Bilateral blindness and low vision was
      noted in 30% and 27.5% of patients, respectively. The average age of patients
      with low vision was 40.38 +/- 16.27 years and the average age of those with
      bilateral blindness was 51.08 +/- 15.79 years. Retinitis pigmentosa was bilateral
      in all cases and isolated (without any eye or general additional disease) in
      67.5% of cases. CONCLUSION: Visual impairment is common and becomes even more
      severe with aging. Patients should be screened to enable them to benefit from
      management focusing on both appropriate treatment and genetic counseling.

PMID- 20689780
TI  - Regression of macular edema secondary to branch retinal vein occlusion during
      anti-TNF-alpha therapy for rheumatoid arthritis.
AB  - A patient with macular edema secondary to a branch retinal vein occlusion (BRVO)
      was treated with intravenous injections of infliximab, an antitumor necrosis
      factor (TNF)-alpha antibody, for her rheumatoid arthritis (RA). Before the
      injection, the thickness of the right fovea, determined by optical coherent
      tomography, was 629 mum and the best-corrected visual acuity (BCVA) was 20/50.
      After eight injections of infliximab and 10 months after the first injection, her
      foveal thickness was decreased to 293 mum and the visual acuity improved to
      20/20. There was no recurrence of macular edema during the infliximab injections.
      However, the infliximab injection was stopped because the patient developed
      pneumonia. Eight months after stopping the infliximab injection, her foveal
      thickness increased to 494 mum. To treat the RA, her orthopedists began weekly
      subcutaneous injections of etanercept, a fusion protein of a section of the TNF
      receptor and immunoglobulin. Five months later, the foveal thickness had
      decreased to 260 mum, and the visual acuity remained at 20/25(+). Because TNF
      alpha is known to break down the blood-retinal barrier, the improvements in our
      case suggest that TNF-alpha plays a role in the pathogenesis of macular edema in
      some patients with BRVO.

PMID- 20689781
TI  - Palpation by blind examiners: A novel approach for glaucoma screening.
AB  - Although there are several risk factors for glaucoma, elevated intraocular
      pressure (IOP) remains the major risk factor. Palpation is one of the oldest,
      simplest, and least expensive methods for approximate IOP assessment. Researchers
      believe that blind individuals may possess a more acutely developed sense of
      touch, which has already proved to be beneficial in clinical breast examination
      to detect early breast cancer. Based on successful findings of a project that
      used blind and visually impaired individuals as breast examiners, we hypothesize
      that blind individuals may also serve as successful examiners for estimation of
      IOP using tactile palpation.

PMID- 20689782
TI  - Azithromycin in DuraSite for the treatment of blepharitis.
AB  - Blepharitis is a common inflammatory disease of the eyelid. Posterior blepharitis
      affects the posterior lamella of the eyelid and involves inflammation of the
      meibomian glands, whereas anterior blepharitis affects the anterior lamella of
      the eyelid and the eyelashes; either version can be inflammatory or infectious in
      nature. Each of these conditions can incite or propagate the other; anterior
      blepharitis, if not treated, can lead to meibomian gland disease, and vice versa.
      Blepharitis is typically chronic, and can be associated with a variety of
      systemic diseases such as dermatitis, as well as ocular diseases such as dry eye,
      conjunctivitis, or keratitis. The standard treatment regimen historically
      consists of lid hygiene with warm compresses and eyelid scrubs, although these
      treatment modalities may have limited efficacy for many patients, especially
      those with more severe disease. Adjunctive treatment includes systemic and
      topical antibiotics, topical corticosteroids, and tear replacement therapy.
      Topical antibiotics are recommended to decrease the bacterial load, and topical
      corticosteroids may help in cases of severe inflammation. Azithromycin ophthalmic
      solution 1% in DuraSite((R)) (AzaSite((R)); Inspire Pharmaceuticals, Durham,
      North Carolina, USA) has been proposed as a novel treatment for posterior
      blepharitis, based on its well-known anti-infective profile, its anti
      inflammatory properties, its excellent tissue penetration, and its regulatory
      approval for the treatment of bacterial conjunctivitis. This review focuses on an
      off-label indication for topical azithromycin 1% in DuraSite for the treatment of
      blepharitis.

PMID- 20689783
TI  - Assessment of macular function by multifocal electroretinography following
      epiretinal membrane surgery with internal limiting membrane peeling.
AB  - The aim of the current study was to evaluate macular function before and after
      surgery for idiopathic epiretinal membranes with internal limiting membrane (ILM)
      peeling by means of multifocal electroretinography (ERG). Eighteen eyes of 18
      patients who underwent vitrectomy with ILM removal were included. Best corrected
      visual acuity, optical coherence tomography (OCT), and multifocal
      electroretinography were assessed prior to surgery, and 3 and 12 months after
      surgery. All surgical samples were obtained and confirmed inclusion of an ILM by
      electron microscopy. Visual acuity and the central foveal thickness by OCT
      improved significantly 3 months postoperatively, with gradual recovery by 12
      months. Preoperatively, only the P1 amplitude in rings 1 and 2 were decreased
      compared with the normal fellow eyes (P < 0.01). Three and 12 months after
      surgery, the P1 amplitude in rings 1 and 2 were decreased compared with the
      preoperative P1 amplitudes, but without significance. The photoreceptor status by
      OCT was related to the N1 amplitude before and after surgery. Although visual
      acuity and macular edema were improved after surgery, macular function, as
      indicated by multifocal ERG, had limited recovery at 12 months.

PMID- 20689784
TI  - Results of a modified non-penetrating deep sclerectomy in the treatment of open
      angle glaucoma with or without cataract.
AB  - PURPOSE: To present the technique of a modified deep sclerectomy, which we will
      call "reversed" deep sclerectomy (RDS) and the results and our observations of
      its use in patients with open angle glaucoma (OAG) and with or without cataract
      extraction (phacoemulsification). MATERIALS AND METHODS: This prospective study
      included 132 eyes which underwent RDS: 37 eyes (group A) with uncontrolled OAG
      and 95 eyes (group B) with OAG and visually significant cataract. Mean pressure
      preoperatively for group A was 24.48 +/- 4.92 mmHg and for group B was 22.99 +/-
      3.00. The mean number of antiglaucoma drugs received was 2.97 +/- 0.69 and 2.56
      +/- 0.73 for groups A and B respectively. The RDS was performed where the deep
      scleral stroma is prepared in 2 parts, folded and inserted under the lateral
      sides of the sclerectomy, and the Schlemm's canal is opened prior to deep scleral
      stroma preparation. Cataract was extracted by phacoemulsification through the
      same scleral opening. The follow-up for group A was 22.23 +/- 10.18 months and
      for group B, 25.36 +/- 10.12 months. RESULTS: Postoperative intraocular pressure
      (IOP) </= 21 mmHg was achieved for group A in 40.5% without antiglaucoma drugs
      and 94.6% with antiglaucoma drugs, and for group B in 66.3% and in 94.7%
      respectively. Mean IOP reduction was 7.02 +/- 6.35 mmHg (28.67%, P < 0.05) for
      group A and 5.26 +/- 3.72 mmHg (25.06%, P </= 0.05) for group B, while mean drug
      reduction was 1.97 +/- 1.09 (P < 0.01) and 2.14 +/- 0.95 (P </= 0.01)
      respectively. 5-Fluorouracil was used in 8 eyes of group A and in 5 eyes of group
      B. CONCLUSION: In the follow-up time during which the two groups were under
      study, the RDS was effective with a few complications, similar to the classic
      deep sclerectomy using implants or not, with the advantage, in our opinion, of a
      short learning curve.

PMID- 20689785
TI  - Concomitant bilateral intravitreal anti-VEGF injections for the treatment of
      exudative age-related macular degeneration.
AB  - PURPOSE: To report the outcomes of same-day, bilateral intravitreal anti-vascular
      endothelial growth factor (VEGF) therapy for a consecutive series of patients
      treated for exudative age-related macular degeneration (ARMD). METHODS: A
      consecutive series of 254 eyes of 127 patients received bilateral, same-day anti
      VEGF injections of either bevacizumab or ranibizumab between January 1, 2007 and
      July 1, 2008 and the outcomes were assessed. Approval was obtained from the
      Institutional Review Board at the University of Miami Miller School of Medicine.
      RESULTS: Bilateral, same-day anti-VEGF injections were well tolerated in all
      patients receiving the therapy. Indication for injection was exudative macular
      degeneration in all patients. The incidence of adverse effects was low, with only
      four events reported, none of which were serious. CONCLUSIONS: In this study,
      bilateral anti-VEGF injections performed on the same day were preferred over
      staggered injections and were well tolerated by patients. No major systemic or
      ocular adverse events were noted, despite the presence of risk factors in a
      subset of patients. Given that there are serious, albeit rare, complications
      following anti-VEGF injection, further study with a larger number of patients
      will be necessary to definitively prove the safety of this treatment modality.

PMID- 20689786
TI  - Crystallization after intravitreal ganciclovir injection.
AB  - PURPOSE: To report crystal formation as a complication of intravitreal
      ganciclovir injection. PATIENTS AND METHODS: A 73-year-old female patient with
      unilateral cytomegalovirus retinitis was treated with intravitreous ganciclovir
      (4 mg/0.04 mL). RESULTS: After the intravitreal injection, sudden crystallization
      was observed in the vitreous humor. The patient experienced marked reduction in
      visual acuity and increased intraocular pressure. Despite aqueous paracenthesis
      and pars plana vitrectomy, optic atrophy was observed and her visual acuity
      remained unimproved after 12 months. CONCLUSION: Crystal formation can occur as a
      complication of intravitreal ganciclovir injection. Associated retinal and optic
      nerve damage was found which results in permanent visual morbidity.

PMID- 20689787
TI  - Oculocutaneous anthrax: detection and treatment.
AB  - Anthrax, a zoonotic disease that primarily affects herbivores, has received
      recent attention as a potential agent of bioterrorism. We report a patient who
      presented with a 4-day history of pain, watering and difficulty in opening the
      left upper and lower eyelids, and fever. Clinical examination revealed brawny
      nonpitting edema with serosanguinous discharge. The history of the death of his
      sheep 1 week prior to the illness provided the clue to the diagnosis. Although
      standard cultures of the blood and the serous fluid from the lesion were
      negative, probably as a result of prior treatment, the diagnosis of cutaneous
      anthrax was made by a polymerase chain reaction (PCR) test of the serous fluid.
      Serial photographs demonstrating resolution of the lesion with appropriate
      antibiotic therapy are presented.

PMID- 20689788
TI  - Central corneal thickness and intraocular pressure in the Cameroonian
      nonglaucomatous population.
AB  - AIM: We performed a prospective, analytical study from 01 January to 31 March
      2009 in the Ophthalmology Unit of the Gyneco-Obstetric and Pediatric Hospital of
      Yaounde, aiming to determine the profile of central corneal thickness (CCT) in
      the Cameroonian nonglaucomatous black population and its relationship with
      intraocular pressure (IOP). RESULTS AND DISCUSSION: Four hundred and eighty-five
      patients (970 eyes) meeting our inclusion criteria were selected for this study.
      The average CCT was 529.29 +/- 35.9 mum in the right eye (95% confidence interval
      [CI]: 526.09-532.49), 528.19 +/- 35.9 mum in the left eye (95% CI: 524.99-531.40)
      and 528.74 +/- 35.89 mum in both eyes (95% CI: 526.48-531.00), range 440 to 670
      mum. The average IOP was 13.01 +/- 2.97 mmHg in both eyes (95% CI: 12.82-13.19).
      A rise in CCT by 100 mum was followed by an increase in IOP of about 2.8 mmHg
      (95% CI: 2.3-3.6) for both eyes taken together. Linear regression analysis showed
      that corneal thickness was negatively correlated with age and IOP was positively
      related with age. CONCLUSION: CCT in the Cameroonian nonglaucomatous black
      population was found to be lower compared with CCT values in Caucasian and Asian
      populations. On the basis of reference values ranging between 527 and 560 mum, an
      adjustment of IOP values by a correction factor is required for many Cameroonian
      patients. This will improve the diagnosis and follow-up of glaucoma by helping to
      detect true ocular hypertension.

PMID- 20689789
TI  - Age-related changes of ocular parameters in Korean subjects.
AB  - AIMS: To evaluate the age-related variations of ocular parameters in Korean
      subjects. METHODS: We recruited 314 normal subjects who visited the department of
      Ophthalmology between January 2007 and October 2007. Refraction, axial length,
      corneal curvature, white-to-white distance, anterior chamber depth, corneal
      endothelial cell density, and retinal nerve fiber layer (RNFL) thickness were
      measured using auto-refractive keratometer, intraocular lens master, noncontact
      specular microscope, and optical coherence tomography. RESULT: In correlation
      analysis, from 19 to 82 years, hyperopic shift showed a strong positive
      statistical correlation with age (r = 0.553, P < 0.001). Corneal curvatures
      increased (r = 0.221, P < 0.001), while axial length (r = -0.506, P < 0.001),
      anterior chamber depth (r = -0.491, P < 0.001) and white-to-white distance (r = 
      0.205, P < 0.001) decreased with age. Also, corneal endothelial cell density was
      lower in older patients than in younger patients (r = -0.409, P < 0.001).
      Compared to younger patients, RNFL thickness was lower in the older patients as
      well, in all quadrants (superior, r = -0.283, P < 0.001; inferior, r = -0.230, P
      < 0.001; nasal, r = 0.025, P = 0.676; and temporal, r = -0.393, P < 0.001).
      According to multiple regression analysis, out of the six parameters measured,
      only hyperopic shift, anterior chamber depth and corneal endothelial cell density
      (P < 0.05) had statistically significant correlation with age. CONCLUSION: Some
      of the ocular parameters changed with aging. Hyperopic shift, shallowing anterior
      chamber depth, and reduction of corneal endothelial cell density were only
      definitely related to age.

PMID- 20689790
TI  - Measurement of treatment compliance using a medical device for glaucoma patients
      associated with intraocular pressure control: a survey.
AB  - OBJECTIVE: To identify and characterize treatment compliance profiles of glaucoma
      patients and evaluate the association with intraocular pressure (IOP). METHODS: A
      computerized device (Travalert((R))) that recorded daily instillation times and
      eye-drop counts was given for 3 months. Patients were declared compliant when at
      least 2 drops were instilled per day. Compliance rates were calculated for
      weekdays and weekends, separately, over 8 consecutive weeks. A principal
      components analysis (PCA) was followed by an ascendant hierarchical
      classification (AHC) to identify compliance groups. RESULTS: 140 patients were
      recruited (mean age 65.5 years; 51.8% female) of whom 83.6% had primary open
      angle glaucoma with mean IOP 23.9 mmHg before Travalert((R)) use. 60.7% were
      treated with DuoTrav((R)) (travoprost timolol fixed combination) and 39.3% with
      travoprost. The PCA identified two axes (compliance and treatment weeks). The AHC
      identified 3 compliance groups: 'high' (56.6%, approx. 80% compliance), 'medium'
      (21.2%, approx. 50% compliance), and 'low' (22.1%, approx. 20% compliance).
      Demographics and glaucoma parameters did not predict low compliance. Final mean
      IOP was 16.1 mmHg, but higher in the low compliance group (17.7 mmHg, P = 0.02).
      CONCLUSIONS: Compliance measurement by a medical device showed compliance rates
      <80% by 50% (approx.) of patients, significantly impacting IOP control. No
      demographic or glaucoma variable was associated with low compliance.

PMID- 20689792
TI  - Correlation between morphology of optic disc determined by Heidelberg Retina
      Tomograph II and visual function in eyes with open-angle glaucoma.
AB  - PURPOSE: To investigate the correlation between the morphology of the optic disc
      and the visual function of eyes with open-angle glaucoma (OAG). PATIENTS AND
      METHODS: One hundred and three eyes of 76 patients with OAG were studied. The
      baseline optic disc morphology was used to classify the eyes into four types:
      focal ischemic type (FI), myopic glaucomatous type (MY), senile sclerotic type
      (SS), and generalized enlargement type (GE). The morphological parameters of the
      disc were determined by the Heidelberg Retina Tomograph II (HRT-II) and the
      visual function by the mean deviation (MD) of the Humphrey field analyzer.
      RESULTS: Fourteen eyes were classified as the FI type; 52 as the MY type; 17 as
      the SS type; and 20 as the GE type. The highest correlation coefficients of HRT
      II parameters to the MDs was the cup/disc area ratio (r = -0.27) for all groups,
      the vertical cup/disc ratio (r = -0.42) in the MY group, the maximum cup depth (r
      = 0.49) in the SS group, and the cup area (r = -0.70) in the GE group. However,
      none of the parameters was correlated in the FI group. CONCLUSIONS: The
      correlation between the HRT-II parameters and MDs was different for the four disc
      types. These findings suggest that a classification of optic disc morphology had
      a benefit for interpreting the measured values of HRT-II.

PMID- 20689793
TI  - Case of endophthalmitis following intravitreal injections of bevacizumab.
AB  - PURPOSE: We report a case of infectious endophthalmitis that developed after the
      third intravitreal injection of bevacizumab. The endophthalmitis was caused by
      Staphylococcus epidermidis. METHODS: Observational case series. RESULTS: This was
      a case of a 77-year-old man who had received three intravitreal injections of
      bevacizumab and developed infectious endophthalmitis. Polymerase chain reaction
      of an aqueous humor sample showed that the endophthalmitis was caused by S.
      epidermidis. The patient received intravitreal ceftazidime and vancomycin, and
      subconjunctival injection of vancomycin. After the intravitreal injections he was
      treated with topical levofloxacin and cefmenoxime hydrochloride, and intravenous
      cefpirome. Subsequently, the ocular inflammation gradually decreased and his
      visual acuity remained at 30/200. CONCLUSIONS: Our findings indicate that
      endophthalmitis can develop after intravitreal bevacizumab injections. Polymerase
      chain reaction is useful for differentiation from sterile endophthalmitis.

PMID- 20689794
TI  - Electroretinographic findings in transplant chorioretinopathy.
AB  - AIM: Transplant chorioretinopathy is a rare complication following solid organ or
      bone marrow transplantation and can result in severe vision loss. This series
      presents electroretinogram (ERG) results in patients with this condition.
      METHODS: Patients who presented with bilateral vision loss following bone marrow
      or solid organ transplantation were identified. A complete ophthalmologic
      examination, fundus photography, and fluorescein angiography (FA) were performed.
      Full-field ERG was obtained in all patients and a multifocal ERG (mfERG) was
      obtained in two patients. RESULTS: Four patients were identified. All patients
      had bilateral vision loss and displayed a characteristic pattern of mottled
      hyperfluorescence on FA. Three patients developed progressive vision loss ranging
      from 20/60 to hand motions whereas one retained 20/40 vision. All patients
      exhibited moderate to severe cone dysfunction, while the degree of rod
      abnormalities was varied. Two patients with severe cone dysfunction showed mild
      clinical changes initially, but later developed progressive vision loss and
      chorioretinal atrophy. CONCLUSION: Transplant chorioretinopathy patients
      undergoing ERG testing show cone dysfunction with a variable degree of rod
      dysfunction. ERG abnormalities preceded the visual acuity and clinical changes in
      two patients, suggesting that ERG may be a helpful predictor of the clinical
      course in this rare disease.

PMID- 20689795
TI  - Treatment of keratoectasia after LASIK by intrastromal corneal ring segments in
      two patients who had no preoperative risk factors.
AB  - PURPOSE: To report on keratoectasia after laser in situ keratomileusis (LASIK) in
      two eyes of two patients who had no obvious preoperative risk factors, and
      treatment of keratoectasia by intrastromal corneal ring segments. METHOD:
      Clinical interventional case report. RESULTS: Two patients underwent LASIK in
      both eyes at Shinagawa LASIK center, Tokyo. Preoperative standard
      ophthalmological examinations demonstrated no specific risk factors of
      keratoectasia. However, each eye of the two patients developed keratoectasia as
      defined by corneal topography. Treatment for keratoectasia was performed by
      inserting intrastromal corneal ring segments (ICRS) in the affected eyes. In one
      eye, KeraRing (MEDIPHACOS, Ltd, Brazil) was inserted, and Intacs SK (Addition
      Technology Inc, USA) was inserted in the other. CONCLUSION: Even in eyes where no
      risk factors for keratoectasia were found following thorough preoperative
      examinations, keratoectasia could develop after LASIK. ICRS could be effective
      for the treatment of keratoectasia after LASIK.

PMID- 20689791
TI  - Clinical utility and differential effects of prostaglandin analogs in the
      management of raised intraocular pressure and ocular hypertension.
AB  - Prostaglandin analogs (PGA) are powerful topical ocular hypotensive agents
      available for the treatment of elevated intraocular pressure (IOP). Latanoprost
      0.005% and travoprost 0.004% are prodrugs and analogs of prostaglandin F2alpha.
      Bimatoprost 0.03% is regarded as a prostamide, and debate continues as to whether
      it is a prodrug. The free acids of all 3 PGAs reduce IOP by enhancing uveoscleral
      and trabecular outflow via direct effects on ciliary muscle relaxation and
      remodeling of extracellular matrix. The vast majority of clinical trials
      demonstrate IOP-lowering superiority of latanoprost, bimatoprost and travoprost
      compared with timolol 0.5%, brimonidine 0.2%, or dorzolamide 2% monotherapy.
      Bimatoprost appears to be more efficacious in IOP-lowering compared with
      latanoprost, with weighted mean difference in IOP reduction documented in one
      meta-analysis of 2.59% to 5.60% from 1- to 6-months study duration. PGAs reduce
      IOP further when used as adjunctive therapy. Fixed combinations of latanoprost,
      bimatoprost or travoprost formulated with timolol 0.5% and administered once
      daily are superior to monotherapy of its constituent parts. PGA have near absence
      of systemic side effects, although do have other commonly encountered ocular
      adverse effects. The adverse effects of PGA, and also those found more frequently
      with bimatoprost use include ocular hyperemia, eyelash growth, and peri-ocular
      pigmentary changes. Iris pigmentary change is unique to PGA treatment. Once daily
      administration and near absence of systemic side effects enhances tolerance and
      compliance. PGAs are often prescribed as first-line treatment for ocular
      hypertension and open-angle glaucoma.

PMID- 20689796
TI  - Monozygotic twins with polypoidal choroidal vasuculopathy.
AB  - PURPOSE: To present the first findings in the set of monozygotic twins with
      polypoidal choroidopathy (PCV). METHODS: Sixty two-year old monozygotic twin
      sisters were studied. The concordances and discordances of the clinical features
      of the twins were determined. Genomic DNA was extracted and genotyped for three
      established PCV risk-associated single nucleotide polymorphisms, viz CFH I62V,
      CFH Y402H, and ARMS A69S. RESULTS: Both patients had hemorrhagic pigment
      epithelial detachments with orange lesions beneath the retinal pigment
      epithelium. Indocyanine green angiography showed pathognomonic choroidal vascular
      networks with polypoidal structures uniocularly in one twin and binocularly in
      the other twin. Both twins were treated with photodynamic therapy, retinal
      photocoagulation, and anti-vascular endothelial growth factor therapy, but both
      showed limited response to all the treatments, with recurrent exudative lesions
      with enlarged vascular network, and poor visual outcome. Genetic analyses showed
      that both sisters had homozygous risk alleles for ARMS2 A69S, and one risk allele
      each of CFH I62V and CFH Y402H. CONCLUSIONS: We present the first findings in a
      set of monozygotic twins with typical PCV under long-term observation. The
      concordances in disease progression and response to treatment between the twins
      indicate that these genetic factors most likely played important roles in
      determining the clinical manifestations.

PMID- 20689797
TI  - 5-Fluorouracil for the treatment of intraepithelial neoplasia and squamous cell
      carcinoma of the conjunctiva, and cornea.
AB  - OBJECTIVE: To evaluate the efficacy and risks of complications of pulse dosing of
      topical 5-fluorouracil (5-FU) in the treatment of corneal intraepithelial
      neoplasia (CIN), and conjunctival squamous cell carcinoma (SCC). DESIGN:
      Prospective, noncomparative case series. PARTICIPANTS: Fifteen patients with
      histological evidence CIN or SCC of the conjunctiva and cornea were identified by
      tumor biopsy. METHODS: All patients clinically evident of CIN, or SCC were
      evaluated, with maximum 30 months of follow-up were treated with pulsed dosing of
      1% 5-FU. Treatment cycles were defined as four times per day for 4 days using the
      medication followed by 30 days without medication. The number of initial
      treatment was six cycles. RESULTS: The mean age of the 15 patients was 50.8 years
      (range 25-78 years). Excision biopsy proved seven cases as CIN, and eight cases
      as locally invasive SCC. All patients remained disease free with a mean follow-up
      of 14.53 months (range 6-30 months). Additional chemotherapy was given after the
      initial treatment cycles, only for one case. 5-FU caused mild temporary local
      irritation, but no long-term intraocular or extra ocular complications.
      CONCLUSIONS: Adjuvant 1% topical 5-FU appears to be effective in the prevention
      of recurrence of conjunctival or corneal CIN and SCC after excision biopsy. Our
      results indicate that at least six cycles of topical 1% 5-FU is required to
      prevent local recurrence in the long term. It is well-tolerated and an effective
      method of treatment. No complications that would preclude use of our dose regimen
      were noted.

PMID- 20689798
TI  - Retinal vein occlusion: pathophysiology and treatment options.
AB  - This paper reviews the current thinking about retinal vein occlusion. It gives an
      overview of its pathophysiology and discusses the evidence behind the various
      established and emerging treatment paradigms.

PMID- 20689799
TI  - The significance of the determination of lymphocytes with clinical manifestation
      of ophthalmic zoster sine herpete.
AB  - OBJECTIVE: To examine the significance of VZV-IgG (IgG) enzyme immunoassay (EIA)
      and the determination of peripheral blood lymphocyte counts in the diagnosis of
      ophthalmic zoster sine herpete (ophthalmic ZSH). METHOD: Clinical case-control
      study with a sample of 65 patients with ophthalmic ZSH (16 males and 49 females;
      mean age 56 +/- 18 years) in whom pressure elicited pain in tender points of
      Valleix (tender points of sites at which the trigeminal nerve appears
      subcutaneously). A total of 41 healthy controls (17 males and 24 females, mean
      age 48 +/- 21 years) were also recruited. In each group, IgG and lymphocyte count
      were determined upon receiving the consent of patients. Multiple logistic
      regression analysis was used to evaluate the factors associated with diagnosis of
      ophthalmic ZSH. Odds ratios and 95% confidence intervals (CI) were determined for
      each variable. RESULTS: Lymphocyte count in the patients with ophthalmic ZSH was
      significantly low, though there were no significant differences in age, gender,
      and IgG between the two groups. Multiple logistic regression analysis revealed
      that lymphocytes pose a significant prognostic factor, and in case of 1,800
      lymphocytes/mul or more, the odds ratio to less than1,800 lymphocytes/mul was
      0.29 (95% CI: 0.12-0.72). CONCLUSION: Patients with orbital pain should be
      suspected as having ophthalmic ZSH as this allows for the determination of
      lymphocyte counts after tender points were confirmed. The swift diagnosis of
      ophthalmic ZSH and the administration of antiviral drugs from an early stage
      improve the subjective symptoms of the patient and is regarded as necessary to
      reduce the risk of severe complications.

PMID- 20689800
TI  - Ecology: a prerequisite for malaria elimination and eradication.

PMID- 20689801
TI  - A short receptor downregulates JAK/STAT signalling to control the Drosophila
      cellular immune response.
AB  - The posterior signalling centre (PSC), a small group of specialised cells,
      controls hemocyte (blood cell) homeostasis in the Drosophila larval hematopoietic
      organ, the lymph gland. This role of the PSC is very reminiscent of the "niche,"
      the micro-environment of hematopoietic stem cells in vertebrates. We have
      recently shown that the PSC acts in a non-cell-autonomous manner to maintain
      janus tyrosine kinase/signal transducers and activators of transcription
      (JAK/STAT) signalling in hematopoietic progenitors (prohemocytes), thereby
      preserving the multipotent character necessary for their differentiation into
      lamellocytes, a cryptic and dedicated immune cell type required to fight specific
      immune threats such as wasp parasitism. In this report, on the basis of a knock
      out generated by homologous recombination, we show that a short type I cytokine
      related receptor CG14225/Latran is required for switching off JAK/STAT signalling
      in prohemocytes. This is a prerequisite to massive differentiation of
      lamellocytes upon wasp parasitisation. In vivo and cell culture assays indicate
      that Latran forms heteromers with Domeless, the Drosophila type I cytokine
      signalling receptor related to mammalian GP130, and antagonises Domeless activity
      in a dose-dependent manner. Our analysis further shows that a primary immune
      response to wasp parasitism is a strong decrease in cytokine mRNA levels in the
      lymph gland, followed by an increase in the latran/domeless ratio. We propose
      that this sequence of events culminates in the complete inhibition of residual
      JAK/STAT signalling by Latran. JAK/STAT activity has been associated with several
      human diseases including leukaemia while knock-out studies in mice point to a
      central role of this pathway in hematopoiesis and regulation of immune functions.
      The specific function of Drosophila Latran is, to our knowledge, the first in
      vivo example of a role for a nonsignalling receptor in controlling a dedicated
      immune response, and thus raises the question of whether short, nonsignalling
      receptors also control specific aspects of vertebrate cellular immunity.

PMID- 20689802
TI  - Motor preparatory activity in posterior parietal cortex is modulated by
      subjective absolute value.
AB  - For optimal response selection, the consequences associated with behavioral
      success or failure must be appraised. To determine how monetary consequences
      influence the neural representations of motor preparation, human brain activity
      was scanned with fMRI while subjects performed a complex spatial visuomotor task.
      At the beginning of each trial, reward context cues indicated the potential gain
      and loss imposed for correct or incorrect trial completion. FMRI-activity in
      canonical reward structures reflected the expected value related to the context.
      In contrast, motor preparatory activity in posterior parietal and premotor cortex
      peaked in high "absolute value" (high gain or loss) conditions: being highest for
      large gains in subjects who believed they performed well while being highest for
      large losses in those who believed they performed poorly. These results suggest
      that the neural activity preceding goal-directed actions incorporates the
      absolute value of that action, predicated upon subjective, rather than objective,
      estimates of one's performance.

PMID- 20689804
TI  - A new type of proton coordination in an F(1)F(o)-ATP synthase rotor ring.
AB  - We solved the crystal structure of a novel type of c-ring isolated from Bacillus
      pseudofirmus OF4 at 2.5 A, revealing a cylinder with a tridecameric
      stoichiometry, a central pore, and an overall shape that is distinct from those
      reported thus far. Within the groove of two neighboring c-subunits, the conserved
      glutamate of the outer helix shares the proton with a bound water molecule which
      itself is coordinated by three other amino acids of outer helices. Although none
      of the inner helices contributes to ion binding and the glutamate has no other
      hydrogen bonding partner than the water oxygen, the site remains in a stable, ion
      locked conformation that represents the functional state present at the c
      ring/membrane interface during rotation. This structure reveals a new, third type
      of ion coordination in ATP synthases. It appears in the ion binding site of an
      alkaliphile in which it represents a finely tuned adaptation of the proton
      affinity during the reaction cycle.

PMID- 20689803
TI  - Rac1-dependent collective cell migration is required for specification of the
      anterior-posterior body axis of the mouse.
AB  - Cell migration and cell rearrangements are critical for establishment of the body
      plan of vertebrate embryos. The first step in organization of the body plan of
      the mouse embryo, specification of the anterior-posterior body axis, depends on
      migration of the anterior visceral endoderm from the distal tip of the embryo to
      a more proximal region overlying the future head. The anterior visceral endoderm
      (AVE) is a cluster of extra-embryonic cells that secretes inhibitors of the Wnt
      and Nodal pathways to inhibit posterior development. Because Rac proteins are
      crucial regulators of cell migration and mouse Rac1 mutants die early in
      development, we tested whether Rac1 plays a role in AVE migration. Here we show
      that Rac1 mutant embryos fail to specify an anterior-posterior axis and, instead,
      express posterior markers in a ring around the embryonic circumference. Cells
      that express the molecular markers of the AVE are properly specified in Rac1
      mutants but remain at the distal tip of the embryo at the time when migration
      should take place. Using tissue specific deletions, we show that Rac1 acts
      autonomously within the visceral endoderm to promote cell migration. High
      resolution imaging shows that the leading wild-type AVE cells extend long
      lamellar protrusions that span several cell diameters and are polarized in the
      direction of cell movement. These projections are tipped by filopodia-like
      structures that appear to sample the environment. Wild-type AVE cells display
      hallmarks of collective cell migration: they retain tight and adherens junctions
      as they migrate and exchange neighbors within the plane of the visceral endoderm
      epithelium. Analysis of mutant embryos shows that Rac1 is not required for
      intercellular signaling, survival, proliferation, or adhesion in the visceral
      endoderm but is necessary for the ability of visceral endoderm cells to extend
      projections, change shape, and exchange neighbors. The data show that Rac1
      mediated epithelial migration of the AVE is a crucial step in the establishment
      of the mammalian body plan and suggest that Rac1 is essential for collective
      migration in mammalian tissues.

PMID- 20689805
TI  - Impact of community-based maternal health workers on coverage of essential
      maternal health interventions among internally displaced communities in eastern
      Burma: the MOM project.
AB  - BACKGROUND: Access to essential maternal and reproductive health care is poor
      throughout Burma, but is particularly lacking among internally displaced
      communities in the eastern border regions. In such settings, innovative
      strategies for accessing vulnerable populations and delivering basic public
      health interventions are urgently needed. METHODS: Four ethnic health
      organizations from the Shan, Mon, Karen, and Karenni regions collaborated on a
      pilot project between 2005 and 2008 to examine the feasibility of an innovative
      three-tiered network of community-based providers for delivery of maternal health
      interventions in the complex emergency setting of eastern Burma. Two-stage
      cluster-sampling surveys among ever-married women of reproductive age (15-45 y)
      conducted before and after program implementation enabled evaluation of changes
      in coverage of essential antenatal care interventions, attendance at birth by
      those trained to manage complications, postnatal care, and family planning
      services. RESULTS: Among 2,889 and 2,442 women of reproductive age in 2006 and
      2008, respectively, population characteristics (age, marital status, ethnic
      distribution, literacy) were similar. Compared to baseline, women whose most
      recent pregnancy occurred during the implementation period were substantially
      more likely to receive antenatal care (71.8% versus 39.3%, prevalence rate ratio
      [PRR] = 1.83 [95% confidence interval (CI) 1.64-2.04]) and specific interventions
      such as urine testing (42.4% versus 15.7%, PRR = 2.69 [95% CI 2.69-3.54]),
      malaria screening (55.9% versus 21.9%, PRR = 2.88 [95% CI 2.15-3.85]), and
      deworming (58.2% versus 4.1%, PRR = 14.18 [95% CI 10.76-18.71]. Postnatal care
      visits within 7 d doubled. Use of modern methods to avoid pregnancy increased
      from 23.9% to 45.0% (PRR = 1.88 [95% CI 1.63-2.17]), and unmet need for
      contraception was reduced from 61.7% to 40.5%, a relative reduction of 35% (95%
      CI 28%-40%). Attendance at birth by those trained to deliver elements of
      emergency obstetric care increased almost 10-fold, from 5.1% to 48.7% (PRR = 9.55
      [95% CI 7.21-12.64]). CONCLUSIONS: Coverage of maternal health interventions and
      higher-level care at birth was substantially higher during the project period.
      The MOM Project's focus on task-shifting, capacity building, and empowerment at
      the community level might serve as a model approach for similarly constrained
      settings.

PMID- 20689807
TI  - Genetic variation and antioxidant response gene expression in the bronchial
      airway epithelium of smokers at risk for lung cancer.
AB  - Prior microarray studies of smokers at high risk for lung cancer have
      demonstrated that heterogeneity in bronchial airway epithelial cell gene
      expression response to smoking can serve as an early diagnostic biomarker for
      lung cancer. As a first step in applying functional genomic analysis to
      population studies, we have examined the relationship between gene expression
      variation and genetic variation in a central molecular pathway (NRF2-mediated
      antioxidant response) associated with smoking exposure and lung cancer. We
      assessed global gene expression in histologically normal airway epithelial cells
      obtained at bronchoscopy from smokers who developed lung cancer (SC, n = 20),
      smokers without lung cancer (SNC, n = 24), and never smokers (NS, n = 8).
      Functional enrichment analysis showed that the NRF2-mediated, antioxidant
      response element (ARE)-regulated genes, were significantly lower in SC, when
      compared with expression levels in SNC. Importantly, we found that the expression
      of MAFG (a binding partner of NRF2) was correlated with the expression of ARE
      genes, suggesting MAFG levels may limit target gene induction. Bioinformatically
      we identified single nucleotide polymorphisms (SNPs) in putative ARE genes and to
      test the impact of genetic variation, we genotyped these putative regulatory SNPs
      and other tag SNPs in selected NRF2 pathway genes. Sequencing MAFG locus, we
      identified 30 novel SNPs and two were associated with either gene expression or
      lung cancer status among smokers. This work demonstrates an analysis approach
      that integrates bioinformatics pathway and transcription factor binding site
      analysis with genotype, gene expression and disease status to identify SNPs that
      may be associated with individual differences in gene expression and/or cancer
      status in smokers. These polymorphisms might ultimately contribute to lung cancer
      risk via their effect on the airway gene expression response to tobacco-smoke
      exposure.

PMID- 20689808
TI  - A didactic model of macromolecular crowding effects on protein folding.
AB  - A didactic model is presented to illustrate how the effect of macromolecular
      crowding on protein folding and association is modeled using current analytical
      theory and discrete molecular dynamics. While analytical treatments of crowding
      may consider the effect as a potential of average force acting to compress a
      polypeptide chain into a compact state, the use of simulations enables the
      presence of crowding reagents to be treated explicitly. Using an analytically
      solvable toy model for protein folding, an approximate statistical thermodynamic
      method is directly compared to simulation in order to gauge the effectiveness of
      current analytical crowding descriptions. Both methodologies are in quantitative
      agreement under most conditions, indication that both current theory and
      simulation methods are capable of recapitulating aspects of protein folding even
      by utilizing a simplistic protein model.

PMID- 20689809
TI  - Etiology of diarrhea in older children, adolescents and adults: a systematic
      review.
AB  - BACKGROUND: Diarrhea is an important cause of morbidity and mortality in all
      regions of the world and among all ages, yet little is known about the fraction
      of diarrhea episodes and deaths due to each pathogen. METHODOLOGY/PRINCIPAL
      FINDINGS: We conducted a systematic literature review to identify all papers
      reporting the proportion of diarrhea episodes with positive laboratory tests for
      at least one pathogen in inpatient, outpatient and community settings that met
      our inclusion and exclusion criteria. We identified a total of 25,701 papers with
      possible etiology data and after final screening included 22 papers that met all
      inclusion and exclusion criteria. Enterotoxigenic Escherichia coli and V.
      cholerae O1/O139 were the leading causes of hospitalizations. In outpatient
      settings, Salmonella spp., Shigella spp., and E. histolytica were the most
      frequently isolated pathogens. CONCLUSIONS/SIGNIFICANCE: This is the first
      systematic review which has considered the relative importance of multiple
      diarrhea pathogens. The few studies identified suggest that there is a great need
      for additional prospective studies around the world in these age groups to better
      understand the burden of disease and the variation by region.

PMID- 20689810
TI  - Consistency and diversity of spike dynamics in the neurons of bed nucleus of
      stria terminalis of the rat: a dynamic clamp study.
AB  - Neurons display a high degree of variability and diversity in the expression and
      regulation of their voltage-dependent ionic channels. Under low level of synaptic
      background a number of physiologically distinct cell types can be identified in
      most brain areas that display different responses to standard forms of
      intracellular current stimulation. Nevertheless, it is not well understood how
      biophysically different neurons process synaptic inputs in natural conditions,
      i.e., when experiencing intense synaptic bombardment in vivo. While distinct cell
      types might process synaptic inputs into different patterns of action potentials
      representing specific "motifs" of network activity, standard methods of
      electrophysiology are not well suited to resolve such questions. In the current
      paper we performed dynamic clamp experiments with simulated synaptic inputs that
      were presented to three types of neurons in the juxtacapsular bed nucleus of
      stria terminalis (jcBNST) of the rat. Our analysis on the temporal structure of
      firing showed that the three types of jcBNST neurons did not produce
      qualitatively different spike responses under identical patterns of input.
      However, we observed consistent, cell type dependent variations in the fine
      structure of firing, at the level of single spikes. At the millisecond resolution
      structure of firing we found high degree of diversity across the entire spectrum
      of neurons irrespective of their type. Additionally, we identified a new cell
      type with intrinsic oscillatory properties that produced a rhythmic and regular
      firing under synaptic stimulation that distinguishes it from the previously
      described jcBNST cell types. Our findings suggest a sophisticated, cell type
      dependent regulation of spike dynamics of neurons when experiencing a complex
      synaptic background. The high degree of their dynamical diversity has
      implications to their cooperative dynamics and synchronization.

PMID- 20689811
TI  - A critical tryptophan and Ca2+ in activation and catalysis of TPPI, the enzyme
      deficient in classic late-infantile neuronal ceroid lipofuscinosis.
AB  - BACKGROUND: Tripeptidyl aminopeptidase I (TPPI) is a crucial lysosomal enzyme
      that is deficient in the fatal neurodegenerative disorder called classic late
      infantile neuronal ceroid lipofuscinosis (LINCL). It is involved in the
      catabolism of proteins in the lysosomes. Recent X-ray crystallographic studies
      have provided insights into the structural/functional aspects of TPPI catalysis,
      and indicated presence of an octahedrally coordinated Ca(2+). METHODOLOGY:
      Purified precursor and mature TPPI were used to study inhibition by NBS and EDTA
      using biochemical and immunological approaches. Site-directed mutagenesis with
      confocal imaging technique identified a critical W residue in TPPI activity, and
      the processing of precursor into mature enzyme. PRINCIPAL FINDINGS: NBS is a
      potent inhibitor of the purified TPPI. In mammalian TPPI, W542 is critical for
      tripeptidyl peptidase activity as well as autocatalysis. Transfection studies
      have indicated that mutants of the TPPI that harbor residues other than W at
      position 542 have delayed processing, and are retained in the ER rather than
      transported to lysosomes. EDTA inhibits the autocatalytic processing of the
      precursor TPPI. CONCLUSIONS/SIGNIFICANCE: We propose that W542 and Ca(2+) are
      critical for maintaining the proper tertiary structure of the precursor
      proprotein as well as the mature TPPI. Additionally, Ca(2+) is necessary for the
      autocatalytic processing of the precursor protein into the mature TPPI. We have
      identified NBS as a potent TPPI inhibitor, which led in delineating a critical
      role for W542 residue. Studies with such compounds will prove valuable in
      identifying the critical residues in the TPPI catalysis and its structure
      function analysis.

PMID- 20689812
TI  - Prediction of dengue disease severity among pediatric Thai patients using early
      clinical laboratory indicators.
AB  - BACKGROUND: Dengue virus is endemic in tropical and sub-tropical resource-poor
      countries. Dengue illness can range from a nonspecific febrile illness to a
      severe disease, Dengue Shock Syndrome (DSS), in which patients develop
      circulatory failure. Earlier diagnosis of severe dengue illnesses would have a
      substantial impact on the allocation of health resources in endemic countries.
      METHODS AND FINDINGS: We compared clinical laboratory findings collected within
      72 hours of fever onset from a prospective cohort children presenting to one of
      two hospitals (one urban and one rural) in Thailand. Classification and
      regression tree analysis was used to develop diagnostic algorithms using
      different categories of dengue disease severity to distinguish between patients
      at elevated risk of developing a severe dengue illness and those at low risk. A
      diagnostic algorithm using WBC count, percent monocytes, platelet count, and
      hematocrit achieved 97% sensitivity to identify patients who went on to develop
      DSS while correctly excluding 48% of non-severe cases. Addition of an indicator
      of severe plasma leakage to the WHO definition led to 99% sensitivity using WBC
      count, percent neutrophils, AST, platelet count, and age. CONCLUSIONS: This study
      identified two easily applicable diagnostic algorithms using early clinical
      indicators obtained within the first 72 hours of illness onset. The algorithms
      have high sensitivity to distinguish patients at elevated risk of developing
      severe dengue illness from patients at low risk, which included patients with
      mild dengue and other non-dengue febrile illnesses. Although these algorithms
      need to be validated in other populations, this study highlights the potential
      usefulness of specific clinical indicators early in illness.

PMID- 20689813
TI  - Serodiagnosis of Echinococcus spp. infection: explorative selection of diagnostic
      antigens by peptide microarray.
AB  - BACKGROUND: Production of native antigens for serodiagnosis of helminthic
      infections is laborious and hampered by batch-to-batch variation. For
      serodiagnosis of echinococcosis, especially cystic disease, most screening tests
      rely on crude or purified Echinococcus granulosus hydatid cyst fluid. To resolve
      limitations associated with native antigens in serological tests, the use of
      standardized and highly pure antigens produced by chemical synthesis offers
      considerable advantages, provided appropriate diagnostic sensitivity and
      specificity is achieved. METHODOLOGY/PRINCIPAL FINDINGS: Making use of the
      growing collection of genomic and proteomic data, we applied a set of
      bioinformatic selection criteria to a collection of protein sequences including
      conceptually translated nucleotide sequence data of two related tapeworms,
      Echinococcus multilocularis and Echinococcus granulosus. Our approach targeted
      alpha-helical coiled-coils and intrinsically unstructured regions of parasite
      proteins potentially exposed to the host immune system. From 6 proteins of E.
      multilocularis and 5 proteins of E. granulosus, 45 peptides between 24 and 30
      amino acids in length were designed. These peptides were chemically synthesized,
      spotted on microarrays and screened for reactivity with sera from infected
      humans. Peptides reacting above the cut-off were validated in enzyme-linked
      immunosorbent assays (ELISA). Peptides identified failed to differentiate between
      E. multilocularis and E. granulosus infection. The peptide performing best
      reached 57% sensitivity and 94% specificity. This candidate derived from
      Echinococcus multilocularis antigen B8/1 and showed strong reactivity to sera
      from patients infected either with E. multilocularis or E. granulosus.
      CONCLUSIONS/SIGNIFICANCE: This study provides proof of principle for the
      discovery of diagnostically relevant peptides by bioinformatic selection
      complemented with screening on a high-throughput microarray platform. Our data
      showed that a single peptide cannot provide sufficient diagnostic sensitivity
      whereas pooling several peptide antigens improved sensitivity; thus combinations
      of several peptides may lead the way to new diagnostic tests that replace, or at
      least complement conventional immunodiagnosis of echinococcosis. Our strategy
      could prove useful for diagnostic developments in other pathogens.

PMID- 20689814
TI  - IL-33 is produced by mast cells and regulates IgE-dependent inflammation.
AB  - BACKGROUND: IL-33 is a recently characterized IL-1 family cytokine and found to
      be expressed in inflammatory diseases, including severe asthma and inflammatory
      bowl disease. Recombinant IL-33 has been shown to enhance Th2-associated immune
      responses and potently increase mast cell proliferation and cytokine production.
      While IL-33 is constitutively expressed in endothelial and epithelial cells,
      where it may function as a transcriptional regulator, cellular sources of IL-33
      and its role in inflammation remain unclear. METHODOLOGY/PRINCIPAL FINDINGS:
      Here, we identify mast cells as IL-33 producing cells. IgE/antigen activation of
      bone marrow-derived mast cells or a murine mast cell line (MC/9) significantly
      enhanced IL-33. Conversely, recombinant IL-33 directly activated mast cells to
      produce several cytokines including IL-4, IL-5 and IL-6 but not IL-33. We show
      that expression of IL-33 in response to IgE-activation required calcium and that
      ionomycin was sufficient to induce IL-33. In vivo, peritoneal mast cells
      expressed IL-33 and IL-33 levels were significantly lower within the skin of mast
      cell deficient mice, compared to littermate controls. Local activation of mast
      cells promotes edema, followed by the recruitment of inflammatory cells. We
      demonstrate using passive cutaneous anaphylaxis, a mast cell-dependent model,
      that deficiency in ST2 or antibody blockage of ST2 or IL-33 ablated the late
      phase inflammatory response but that the immediate phase response was unaffected.
      IL-33 levels in the skin were significantly elevated only during the late phase.
      CONCLUSIONS/SIGNIFICANCE: Our findings demonstrate that mast cells produce IL-33
      after IgE-mediated activation and that the IL-33/ST2 pathway is critical for the
      progression of IgE-dependent inflammation.

PMID- 20689815
TI  - Screening mosquito house entry points as a potential method for integrated
      control of endophagic filariasis, arbovirus and malaria vectors.
AB  - BACKGROUND: Partial mosquito-proofing of houses with screens and ceilings has the
      potential to reduce indoor densities of malaria mosquitoes. We wish to measure
      whether it will also reduce indoor densities of vectors of neglected tropical
      diseases. METHODOLOGY: The main house entry points preferred by anopheline and
      culicine vectors were determined through controlled experiments using specially
      designed experimental huts and village houses in Lupiro village, southern
      Tanzania. The benefit of screening different entry points (eaves, windows and
      doors) using PVC-coated fibre glass netting material in terms of reduced indoor
      densities of mosquitoes was evaluated compared to the control. FINDINGS: 23,027
      mosquitoes were caught with CDC light traps; 77.9% (17,929) were Anopheles
      gambiae sensu lato, of which 66.2% were An. arabiensis and 33.8% An. gambiae
      sensu stricto. The remainder comprised 0.2% (50) An. funestus, 10.2% (2359) Culex
      spp. and 11.6% (2664) Mansonia spp. Screening eaves reduced densities of
      Anopheles gambiae s. l. (Relative ratio (RR) = 0.91; 95% CI = 0.84, 0.98; P =
      0.01); Mansonia africana (RR = 0.43; 95% CI = 0.26, 0.76; P<0.001) and Mansonia
      uniformis (RR = 0.37; 95% CI = 0.25, 0.56; P<0.001) but not Culex
      quinquefasciatus, Cx. univittatus or Cx. theileri. Numbers of these species were
      reduced by screening windows and doors but this was not significant.
      SIGNIFICANCE: This study confirms that across Africa, screening eaves protects
      households against important mosquito vectors of filariasis, Rift Valley Fever
      and O'Nyong nyong as well as malaria. While full house screening is required to
      exclude Culex species mosquitoes, screening of eaves alone or fitting ceilings
      has considerable potential for integrated control of other vectors of filariasis,
      arbovirus and malaria.

PMID- 20689816
TI  - The international limits and population at risk of Plasmodium vivax transmission
      in 2009.
AB  - BACKGROUND: A research priority for Plasmodium vivax malaria is to improve our
      understanding of the spatial distribution of risk and its relationship with the
      burden of P. vivax disease in human populations. The aim of the research outlined
      in this article is to provide a contemporary evidence-based map of the global
      spatial extent of P. vivax malaria, together with estimates of the human
      population at risk (PAR) of any level of transmission in 2009. METHODOLOGY: The
      most recent P. vivax case-reporting data that could be obtained for all malaria
      endemic countries were used to classify risk into three classes: malaria free,
      unstable (<0.1 case per 1,000 people per annum (p.a.)) and stable (> or =0.1 case
      per 1,000 p.a.) P. vivax malaria transmission. Risk areas were further
      constrained using temperature and aridity data based upon their relationship with
      parasite and vector bionomics. Medical intelligence was used to refine the
      spatial extent of risk in specific areas where transmission was reported to be
      absent (e.g., large urban areas and malaria-free islands). The PAR under each
      level of transmission was then derived by combining the categorical risk map with
      a high resolution population surface adjusted to 2009. The exclusion of large
      Duffy negative populations in Africa from the PAR totals was achieved using
      independent modelling of the gene frequency of this genetic trait. It was
      estimated that 2.85 billion people were exposed to some risk of P. vivax
      transmission in 2009, with 57.1% of them living in areas of unstable
      transmission. The vast majority (2.59 billion, 91.0%) were located in Central and
      South East (CSE) Asia, whilst the remainder were located in America (0.16
      billion, 5.5%) and in the Africa+ region (0.10 billion, 3.5%). Despite evidence
      of ubiquitous risk of P. vivax infection in Africa, the very high prevalence of
      Duffy negativity throughout Central and West Africa reduced the PAR estimates
      substantially. CONCLUSIONS: After more than a century of development and control,
      P. vivax remains more widely distributed than P. falciparum and is a potential
      cause of morbidity and mortality amongst the 2.85 billion people living at risk
      of infection, the majority of whom are in the tropical belt of CSE Asia. The
      probability of infection is reduced massively across Africa by the frequency of
      the Duffy negative trait, but transmission does occur on the continent and is a
      concern for Duffy positive locals and travellers. The final map provides the
      spatial limits on which the endemicity of P. vivax transmission can be mapped to
      support future cartographic-based burden estimations.

PMID- 20689817
TI  - Transgenic overexpression of active calcineurin in beta-cells results in
      decreased beta-cell mass and hyperglycemia.
AB  - BACKGROUND: Glucose modulates beta-cell mass and function through an initial
      depolarization and Ca(2+) influx, which then triggers a number of growth
      regulating signaling pathways. One of the most important downstream effectors in
      Ca(2+) signaling is the calcium/Calmodulin activated serine threonine
      phosphatase, calcineurin. Recent evidence suggests that calcineurin/NFAT is
      essential for beta-cell proliferation, and that in its absence loss of beta-cells
      results in diabetes. We hypothesized that in contrast, activation of calcineurin
      might result in expansion of beta-cell mass and resistance to diabetes.
      METHODOLOGY/PRINCIPAL FINDINGS: To determine the role of activation of
      calcineurin signaling in the regulation of pancreatic beta-cell mass and
      proliferation, we created mice that expressed a constitutively active form of
      calcineurin under the insulin gene promoter (caCn(RIP)). To our surprise, these
      mice exhibited glucose intolerance. In vitro studies demonstrated that while the
      second phase of Insulin secretion is enhanced, the overall insulin secretory
      response was conserved. Islet morphometric studies demonstrated decreased beta
      cell mass suggesting that this was a major component responsible for altered
      Insulin secretion and glucose intolerance in caCn(RIP) mice. The reduced beta
      cell mass was accompanied by decreased proliferation and enhanced apoptosis.
      CONCLUSIONS: Our studies identify calcineurin as an important factor in
      controlling glucose homeostasis and indicate that chronic depolarization leading
      to increased calcineurin activity may contribute, along with other genetic and
      environmental factors, to beta-cell dysfunction and diabetes.

PMID- 20689818
TI  - Gender separation increases somatic growth in females but does not affect
      lifespan in Nothobranchius furzeri.
AB  - According to life history theory, physiological and ecological traits and
      parameters influence an individual's life history and thus, ultimately, its
      lifespan. Mating and reproduction are costly activities, and in a variety of
      model organisms, a negative correlation of longevity and reproductive effort has
      been demonstrated. We are employing the annual killifish Nothobranchius furzeri
      as a vertebrate model for ageing. N. furzeri is the vertebrate displaying the
      shortest known lifespan in captivity with particular strains living only three to
      four months under optimal laboratory conditions. The animals show explosive
      growth, early sexual maturation and age-dependent physiological and behavioural
      decline. Here, we have used N. furzeri to investigate a potential reproduction
      longevity trade-off in both sexes by means of gender separation. Though female
      reproductive effort and offspring investment were significantly reduced after
      separation, as investigated by analysis of clutch size, eggs in the ovaries and
      ovary mass, the energetic surplus was not reallocated towards somatic
      maintenance. In fact, a significant extension of lifespan could not be observed
      in either sex. This is despite the fact that separated females, but not males,
      grew significantly larger and heavier than the respective controls. Therefore, it
      remains elusive whether lifespan of an annual species evolved in periodically
      vanishing habitats can be prolonged on the cost of reproduction at all.

PMID- 20689819
TI  - Skin cornification proteins provide global link between ROS detoxification and
      cell migration during wound healing.
AB  - Wound healing is a complex dynamic process characterised by a uniform flow of
      events in nearly all types of tissue damage, from a small skin scratch to
      myocardial infarction. Reactive oxygen species (ROS) are essential during the
      healing process at multiple stages, ranging from the initial signal that
      instigates the immune response, to the triggering of intracellular redox
      dependent signalling pathways and the defence against invading bacteria.
      Excessive ROS in the wound milieu nevertheless impedes new tissue formation. Here
      we identify small proline-rich (SPRR) proteins as essential players in this
      latter process, as they directly link ROS detoxification with cell migration. A
      literature-based meta-analysis revealed their up-regulation in various forms of
      tissue injury, ranging from heart infarction and commensal-induced gut responses
      to nerve regeneration and burn injury. Apparently, SPRR proteins have a far more
      widespread role in wound healing and tissue remodelling than their established
      function in skin cornification. It is inferred that SPRR proteins provide injured
      tissue with an efficient, finely tuneable antioxidant barrier specifically
      adapted to the tissue involved and the damage inflicted. Their recognition as
      novel cell protective proteins combining ROS detoxification with cell migration
      will provide new venues to study and manage tissue repair and wound healing at a
      molecular level.

PMID- 20689820
TI  - The role of imported cases and favorable meteorological conditions in the onset
      of dengue epidemics.
AB  - BACKGROUND: Travelers who acquire dengue infection are often routes for virus
      transmission to other regions. Nevertheless, the interplay between infected
      travelers, climate, vectors, and indigenous dengue incidence remains unclear. The
      role of foreign-origin cases on local dengue epidemics thus has been largely
      neglected by research. This study investigated the effect of both imported dengue
      and local meteorological factors on the occurrence of indigenous dengue in
      Taiwan. METHODS AND PRINCIPAL FINDINGS: Using logistic and Poisson regression
      models, we analyzed bi-weekly, laboratory-confirmed dengue cases at their onset
      dates of illness from 1998 to 2007 to identify correlations between indigenous
      dengue and imported dengue cases (in the context of local meteorological factors)
      across different time lags. Our results revealed that the occurrence of
      indigenous dengue was significantly correlated with temporally-lagged cases of
      imported dengue (2-14 weeks), higher temperatures (6-14 weeks), and lower
      relative humidity (6-20 weeks). In addition, imported and indigenous dengue cases
      had a significant quantitative relationship in the onset of local epidemics.
      However, this relationship became less significant once indigenous epidemics
      progressed past the initial stage. CONCLUSIONS: These findings imply that
      imported dengue cases are able to initiate indigenous epidemics when appropriate
      weather conditions are present. Early detection and case management of imported
      cases through rapid diagnosis may avert large-scale epidemics of dengue/dengue
      hemorrhagic fever. The deployment of an early-warning surveillance system, with
      the capacity to integrate meteorological data, will be an invaluable tool for
      successful prevention and control of dengue, particularly in non-endemic
      countries.

PMID- 20689821
TI  - Redefining the expression and function of the inhibitor of differentiation 1 in
      mammary gland development.
AB  - The accumulation of poorly differentiated cells is a hallmark of breast neoplasia
      and progression. Thus an understanding of the factors controlling mammary
      differentiation is critical to a proper understanding of breast tumourigenesis.
      The Inhibitor of Differentiation 1 (Id1) protein has well documented roles in the
      control of mammary epithelial differentiation and proliferation in vitro and
      breast cancer progression in vivo. However, it has not been determined whether
      Id1 expression is sufficient for the inhibition of mammary epithelial
      differentiation or the promotion of neoplastic transformation in vivo. We now
      show that Id1 is not commonly expressed by the luminal mammary epithelia, as
      previously reported. Generation and analysis of a transgenic mouse model of Id1
      overexpression in the mammary gland reveals that Id1 is insufficient for
      neoplastic progression in virgin animals or to prevent terminal differentiation
      of the luminal epithelia during pregnancy and lactation. Together, these data
      demonstrate that there is no luminal cell-autonomous role for Id1 in mammary
      epithelial cell fate determination, ductal morphogenesis and terminal
      differentiation.

PMID- 20689822
TI  - Diagnostic accuracy of the Leishmania OligoC-TesT and NASBA-Oligochromatography
      for diagnosis of leishmaniasis in Sudan.
AB  - BACKGROUND: The Leishmania OligoC-TesT and NASBA-Oligochromatography (OC) were
      recently developed for simplified and standardised molecular detection of
      Leishmania parasites in clinical specimens. We here present the phase II
      evaluation of both tests for diagnosis of visceral leishmaniasis (VL), cutaneous
      leishmaniasis (CL) and post kala-azar dermal leishmaniasis (PKDL) in Sudan.
      METHODOLOGY: The diagnostic accuracy of the tests was evaluated on 90 confirmed
      and 90 suspected VL cases, 7 confirmed and 8 suspected CL cases, 2 confirmed PKDL
      cases and 50 healthy endemic controls from Gedarif state and Khartoum state in
      Sudan. PRINCIPAL FINDINGS: The OligoC-TesT as well as the NASBA-OC showed a
      sensitivity of 96.8% (95% CI: 83.8%-99.4%) on lymph node aspirates and of 96.2%
      (95% CI: 89.4%-98.7%) on blood from the confirmed VL cases. The sensitivity on
      bone marrow was 96.9% (95% CI: 89.3%-99.1%) and 95.3% (95% CI: 87.1%-98.4%) for
      the OligoC-TesT and NASBA-OC, respectively. All confirmed CL and PKDL cases were
      positive with both tests. On the suspected VL cases, we observed a positive
      OligoC-TesT and NASBA-OC result in 37.1% (95% CI: 23.2%-53.7%) and 34.3% (95% CI:
      20.8%-50.9%) on lymph, in 72.7% (95% CI: 55.8%-84.9%) and 63.6% (95% CI: 46.6%
      77.8%) on bone marrow and in 76.9% (95% CI: 49.7%-91.8%) and 69.2% (95% CI: 42.4%
      87.3%) on blood. Seven out of 8 CL suspected cases were positive with both tests.
      The specificity on the healthy endemic controls was 90% (95% CI: 78.6%-95.7%) for
      the OligoC-TesT and 100% (95% CI: 92.9%-100.0%) for the NASBA-OC test.
      CONCLUSIONS: Both tests showed high sensitivity on lymph, blood and tissue
      scrapings for diagnosis of VL, CL and PKDL in Sudan, but the specificity for
      clinical VL was significantly higher with NASBA-OC.

PMID- 20689823
TI  - Characterization of the dispersal of non-domiciliated Triatoma dimidiata through
      the selection of spatially explicit models.
AB  - BACKGROUND: Chagas disease is a major parasitic disease in Latin America,
      prevented in part by vector control programs that reduce domestic populations of
      triatomines. However, the design of control strategies adapted to non
      domiciliated vectors, such as Triatoma dimidiata, remains a challenge because it
      requires an accurate description of their spatio-temporal distributions, and a
      proper understanding of the underlying dispersal processes. METHODOLOGY/PRINCIPAL
      FINDINGS: We combined extensive spatio-temporal data sets describing house
      infestation dynamics by T. dimidiata within a village, and spatially explicit
      population dynamics models in a selection model approach. Several models were
      implemented to provide theoretical predictions under different hypotheses on the
      origin of the dispersers and their dispersal characteristics, which we compared
      with the spatio-temporal pattern of infestation observed in the field. The best
      models fitted the dynamic of infestation described by a one year time-series, and
      also predicted with a very good accuracy the infestation process observed during
      a second replicate one year time-series. The parameterized models gave key
      insights into the dispersal of these vectors. i) About 55% of the triatomines
      infesting houses came from the peridomestic habitat, the rest corresponding to
      immigration from the sylvatic habitat, ii) dispersing triatomines were 5-15 times
      more attracted by houses than by peridomestic area, and iii) the moving
      individuals spread on average over rather small distances, typically 40-60 m/15
      days. CONCLUSION/SIGNIFICANCE: Since these dispersal characteristics are
      associated with much higher abundance of insects in the periphery of the village,
      we discuss the possibility that spatially targeted interventions allow for
      optimizing the efficacy of vector control activities within villages. Such
      optimization could prove very useful in the context of limited resources devoted
      to vector control.

PMID- 20689824
TI  - The effect of leflunomide on cycling and activation of T-cells in HIV-1-infected
      participants.
AB  - BACKGROUND: The pathogenesis of immunodeficiency due to human immunodeficiency
      virus (HIV)-1 is incompletely understood, but immune activation is believed to
      play a central role. Immunomodulatory agents that decrease immune activation may
      be useful in the treatment of HIV-1 infection. METHODOLOGY: A randomized, double
      blind, placebo-controlled pilot study of leflunomide for 28 days was performed in
      participants with HIV-1 infection who were not receiving antiretroviral therapy.
      Participants randomized to leflunomide were subsequently treated with
      cholestyramine until leflunomide levels were below detection limit. FINDINGS:
      Treatment with leflunomide was well tolerated with mostly low-grade adverse
      events. Leflunomide administration reduced cycling of CD4 T cells (by ex vivo
      bromodeoxyuridine uptake and Ki67 expression) and decreased expression of
      activation markers (HLA-DR/CD38 co-expression) on CD8 T cells in peripheral
      blood. In addition, decreased expression of HIV-1 co-receptors was observed in
      both CD4 and CD8 T cells in the leflunomide group. There were no significant
      changes in naive and memory T cell subsets, apoptosis of T cells or markers of
      microbial translocation. CONCLUSIONS: Leflunomide was effective in reducing
      immune activation in the setting of chronic HIV-1 infection suggesting that
      targeting immune activation with immunomodulatory agents may be a feasible
      strategy. TRIAL REGISTRATION: ClinicalTrials.gov NCT00101374.

PMID- 20689825
TI  - Cross-reactivity of antibodies against leptospiral recurrent uveitis-associated
      proteins A and B (LruA and LruB) with eye proteins.
AB  - Infection by Leptospira interrogans has been causally associated with human and
      equine uveitis. Studies in our laboratories have demonstrated that leptospiral
      lipoprotein LruA and LruB are expressed in the eyes of uveitic horses, and that
      antibodies directed against LruA and LruB react with equine lenticular and
      retinal extracts, respectively. These reactivities were investigated further by
      performing immunofluorescent assays on lenticular and retinal tissue sections.
      Incubation of lens tissue sections with LruA-antiserum and retinal sections with
      LruB-antiserum resulted in positive fluorescence. By employing two-dimensional
      gel analyses followed by immunoblotting and mass spectrometry, lens proteins
      cross-reacting with LruA antiserum were identified to be alpha-crystallin B and
      vimentin. Similarly, mass spectrometric analyses identified beta-crystallin B2 as
      the retinal protein cross-reacting with LruB-antiserum. Purified recombinant
      human alpha-crystallin B and vimentin were recognized by LruA-directed antiserum,
      but not by control pre-immune serum. Recombinant beta-crystallin B2 was likewise
      recognized by LruB-directed antiserum, but not by pre-immune serum. Moreover,
      uveitic eye fluids contained significantly higher levels of antiibodies that
      recognized alpha-crystallin B, beta-crystallin B2 and vimentin than did normal
      eye fluids. Our results indicate that LruA and LruB share immuno-relevant
      epitopes with eye proteins, suggesting that cross-reactive antibody interactions
      with eye antigens may contribute to immunopathogenesis of Leptospira-associated
      recurrent uveitis.

PMID- 20689826
TI  - Nuclear S100A7 is associated with poor prognosis in head and neck cancer.
AB  - BACKGROUND: Tissue proteomic analysis of head and neck squamous cell carcinoma
      (HNSCC) and normal oral mucosa using iTRAQ (isobaric tag for relative and
      absolute quantitation) labeling and liquid chromatography-mass spectrometry, led
      to the identification of a panel of biomarkers including S100A7. In the multi
      step process of head and neck tumorigenesis, the presence of dysplastic areas in
      the epithelium is proposed to be associated with a likely progression to cancer;
      however there are no established biomarkers to predict their potential of
      malignant transformation. This study aimed to determine the clinical significance
      of S100A7 overexpression in HNSCC. METHODOLOGY: Immunohistochemical analysis of
      S100A7 expression in HNSCC (100 cases), oral lesions (166 cases) and 100
      histologically normal tissues was carried out and correlated with
      clinicopathological parameters and disease prognosis over 7 years for HNSCC
      patients. Overexpression of S100A7 protein was significant in oral lesions
      (squamous cell hyperplasia/dysplasia) and sustained in HNSCC in comparison with
      oral normal mucosa (p(trend)<0.001). Significant increase in nuclear S100A7 was
      observed in HNSCC as compared to dysplastic lesions (p = 0.005) and associated
      with well differentiated squamous cell carcinoma (p = 0.031). Notably, nuclear
      accumulation of S100A7 also emerged as an independent predictor of reduced
      disease free survival (p = 0.006, Hazard ratio (HR = 7.6), 95% CI = 1.3-5.1) in
      multivariate analysis underscoring its relevance as a poor prognosticator of
      HNSCC patients. CONCLUSIONS: Our study demonstrated nuclear accumulation of
      S100A7 may serve as predictor of poor prognosis in HNSCC patients. Further,
      increased nuclear accumulation of S100A7 in HNSCC as compared to dysplastic
      lesions warrants a large-scale longitudinal study of patients with dysplasia to
      evaluate its potential as a determinant of increased risk of transformation of
      oral premalignant lesions.

PMID- 20689827
TI  - Mutation size optimizes speciation in an evolutionary model.
AB  - The role of mutation rate in optimizing key features of evolutionary dynamics has
      recently been investigated in various computational models. Here, we address the
      related question of how maximum mutation size affects the formation of species in
      a simple computational evolutionary model. We find that the number of species is
      maximized for intermediate values of a mutation size parameter mu; the result is
      observed for evolving organisms on a randomly changing landscape as well as in a
      version of the model where negative feedback exists between the local population
      size and the fitness provided by the landscape. The same result is observed for
      various distributions of mutation values within the limits set by mu. When
      organisms with various values of mu compete against each other, those with
      intermediate mu values are found to survive. The surviving values of mu from
      these competition simulations, however, do not necessarily coincide with the
      values that maximize the number of species. These results suggest that various
      complex factors are involved in determining optimal mutation parameters for any
      population, and may also suggest approaches for building a computational bridge
      between the (micro) dynamics of mutations at the level of individual organisms
      and (macro) evolutionary dynamics at the species level.

PMID- 20689828
TI  - Phage-derived fully human monoclonal antibody fragments to human vascular
      endothelial growth factor-C block its interaction with VEGF receptor-2 and 3.
AB  - Vascular endothelial growth factor C (VEGF-C) is a key mediator of
      lymphangiogenesis, acting via its receptors VEGF-R2 and VEGF-R3. High expression
      of VEGF-C in tumors correlates with increased lymphatic vessel density, lymphatic
      vessel invasion, sentinel lymph node metastasis and poor prognosis. Recently, we
      found that in a chemically induced skin carcinoma model, increased VEGF-C
      drainage from the tumor enhanced lymphangiogenesis in the sentinel lymph node and
      facilitated metastatic spread of cancer cells via the lymphatics. Hence,
      interference with the VEGF-C/VEGF-R3 axis holds promise to block metastatic
      spread, as recently shown by use of a neutralizing anti-VEGF-R3 antibody and a
      soluble VEGF-R3 (VEGF-C/D trap). By antibody phage-display, we have developed a
      human monoclonal antibody fragment (single-chain Fragment variable, scFv) that
      binds with high specificity and affinity to the fully processed mature form of
      human VEGF-C. The scFv binds to an epitope on VEGF-C that is important for
      receptor binding, since binding of the scFv to VEGF-C dose-dependently inhibits
      the binding of VEGF-C to VEGF-R2 and VEGF-R3 as shown by BIAcore and ELISA
      analyses. Interestingly, the variable heavy domain (V(H)) of the anti-VEGF-C
      scFv, which contains a mutation typical for camelid heavy chain-only antibodies,
      is sufficient for binding VEGF-C. This reduced the size of the potentially VEGF-C
      blocking antibody fragment to only 14.6 kDa. Anti-VEGF-C V(H)-based
      immunoproteins hold promise to block the lymphangiogenic activity of VEGF-C,
      which would present a significant advance in inhibiting lymphatic-based
      metastatic spread of certain cancer types.

PMID- 20689829
TI  - Transmission of Schistosoma japonicum in marshland and hilly regions of China:
      parasite population genetic and sibship structure.
AB  - The transmission dynamics of Schistosoma japonicum remain poorly understood, as
      over forty species of mammals are suspected of serving as reservoir hosts.
      However, knowledge of the population genetic structure and of the full-sibship
      structuring of parasites at two larval stages will be useful in defining and
      tracking the transmission pattern between intermediate and definitive hosts. S.
      japonicum larvae were therefore collected in three marshland and three hilly
      villages in Anhui Province of China across three time points: April and September
      October 2006, and April 2007, and then genotyped with six microsatellite markers.
      Results from the population genetic and sibling relationship analyses of the
      parasites across two larval stages demonstrated that, within the marshland,
      parasites from cattle showed higher genetic diversity than from other species;
      whereas within the hilly region, parasites from dogs and humans displayed higher
      genetic diversity than those from rodents. Both the extent of gene flow and the
      estimated proportion of full-sib relationships of parasites between two larval
      stages indicated that the cercariae identified within intermediate hosts in the
      marshlands mostly came from cattle, whereas in the hilly areas, they were varied
      between villages, coming primarily from rodents, dogs or humans. Such results
      suggest a different transmission process within the hilly region from within the
      marshlands. Moreover, this is the first time that the sibling relationship
      analysis was applied to the transmission dynamics for S. japonicum.

PMID- 20689830
TI  - Reproductive hormone-dependent and -independent contributions to developmental
      changes in kisspeptin in GnRH-deficient hypogonadal mice.
AB  - Kisspeptin is a potent activator of GnRH-induced gonadotropin secretion and is a
      proposed central regulator of pubertal onset. In mice, there is a neuroanatomical
      separation of two discrete kisspeptin neuronal populations, which are sexually
      dimorphic and are believed to make distinct contributions to reproductive
      physiology. Within these kisspeptin neuron populations, Kiss1 expression is
      directly regulated by sex hormones, thereby confounding the roles of sex
      differences and early activational events that drive the establishment of
      kisspeptin neurons. In order to better understand sex steroid hormone-dependent
      and -independent effects on the maturation of kisspeptin neurons, hypogonadal
      (hpg) mice deficient in GnRH and its downstream effectors were used to determine
      changes in the developmental kisspeptin expression. In hpg mice, sex differences
      in Kiss1 mRNA levels and kisspeptin immunoreactivity, typically present at 30
      days of age, were absent in the anteroventral periventricular nucleus (AVPV).
      Although immunoreactive kisspeptin increased from 10 to 30 days of age to levels
      intermediate between wild type (WT) females and males, corresponding increases in
      Kiss1 mRNA were not detected. In contrast, the hpg arcuate nucleus (ARC)
      demonstrated a 10-fold increase in Kiss1 mRNA between 10 and 30 days in both
      females and males, suggesting that the ARC is a significant center for sex
      steroid-independent pubertal kisspeptin expression. Interestingly, the normal
      positive feedback response of AVPV kisspeptin neurons to estrogen observed in WT
      mice was lost in hpg females, suggesting that exposure to reproductive hormones
      during development may contribute to the establishment of the ovulatory
      gonadotropin surge mechanism. Overall, these studies suggest that the onset of
      pubertal kisspeptin expression is not dependent on reproductive hormones, but
      that gonadal sex steroids critically shape the hypothalamic kisspeptin neuronal
      subpopulations to make distinct contributions to the activation and control of
      the reproductive hormone cascade at the time of puberty.

PMID- 20689831
TI  - Vocal tract articulation in zebra finches.
AB  - BACKGROUND: Birdsong and human vocal communication are both complex behaviours
      which show striking similarities mainly thought to be present in the area of
      development and learning. Recent studies, however, suggest that there are also
      parallels in vocal production mechanisms. While it has been long thought that
      vocal tract filtering, as it occurs in human speech, only plays a minor role in
      birdsong there is an increasing number of studies indicating the presence of
      sound filtering mechanisms in bird vocalizations as well. METHODOLOGY/PRINCIPAL
      FINDINGS: Correlating high-speed X-ray cinematographic imaging of singing zebra
      finches (Taeniopygia guttata) to song structures we identified beak gape and the
      expansion of the oropharyngeal-esophageal cavity (OEC) as potential articulators.
      We subsequently manipulated both structures in an experiment in which we played
      sound through the vocal tract of dead birds. Comparing acoustic input with
      acoustic output showed that OEC expansion causes an energy shift towards lower
      frequencies and an amplitude increase whereas a wide beak gape emphasizes
      frequencies around 5 kilohertz and above. CONCLUSION: These findings confirm that
      birds can modulate their song by using vocal tract filtering and demonstrate how
      OEC and beak gape contribute to this modulation.

PMID- 20689832
TI  - Chemoreception regulates chemical access to mouse vomeronasal organ: role of
      solitary chemosensory cells.
AB  - Controlling stimulus access to sensory organs allows animals to optimize sensory
      reception and prevent damage. The vomeronasal organ (VNO) detects pheromones and
      other semiochemicals to regulate innate social and sexual behaviors. This
      semiochemical detection generally requires the VNO to draw in chemical fluids,
      such as bodily secretions, which are complex in composition and can be
      contaminated. Little is known about whether and how chemical constituents are
      monitored to regulate the fluid access to the VNO. Using transgenic mice and
      immunolabeling, we found that solitary chemosensory cells (SCCs) reside densely
      at the entrance duct of the VNO. In this region, most of the intraepithelial
      trigeminal fibers innervate the SCCs, indicating that SCCs relay sensory
      information onto the trigeminal fibers. These SCCs express transient receptor
      potential channel M5 (TRPM5) and the phospholipase C (PLC) beta2 signaling
      pathway. Additionally, the SCCs express choline acetyltransferase (ChAT) and
      vesicular acetylcholine transporter (VAChT) for synthesizing and packaging
      acetylcholine, a potential transmitter. In intracellular Ca2+ imaging, the SCCs
      responded to various chemical stimuli including high concentrations of odorants
      and bitter compounds. The responses were suppressed significantly by a PLC
      inhibitor, suggesting involvement of the PLC pathway. Further, we developed a
      quantitative dye assay to show that the amount of stimulus fluid that entered the
      VNOs of behaving mice is inversely correlated to the concentration of odorous and
      bitter substances in the fluid. Genetic knockout and pharmacological inhibition
      of TRPM5 resulted in larger amounts of bitter compounds entering the VNOs. Our
      data uncovered that chemoreception of fluid constituents regulates chemical
      access to the VNO and plays an important role in limiting the access of non
      specific irritating and harmful substances. Our results also provide new insight
      into the emerging role of SCCs in chemoreception and regulation of physiological
      actions.

PMID- 20689833
TI  - Turning the table: plants consume microbes as a source of nutrients.
AB  - Interactions between plants and microbes in soil, the final frontier of ecology,
      determine the availability of nutrients to plants and thereby primary production
      of terrestrial ecosystems. Nutrient cycling in soils is considered a battle
      between autotrophs and heterotrophs in which the latter usually outcompete the
      former, although recent studies have questioned the unconditional reign of
      microbes on nutrient cycles and the plants' dependence on microbes for breakdown
      of organic matter. Here we present evidence indicative of a more active role of
      plants in nutrient cycling than currently considered. Using fluorescent-labeled
      non-pathogenic and non-symbiotic strains of a bacterium and a fungus (Escherichia
      coli and Saccharomyces cerevisiae, respectively), we demonstrate that microbes
      enter root cells and are subsequently digested to release nitrogen that is used
      in shoots. Extensive modifications of root cell walls, as substantiated by cell
      wall outgrowth and induction of genes encoding cell wall synthesizing, loosening
      and degrading enzymes, may facilitate the uptake of microbes into root cells. Our
      study provides further evidence that the autotrophy of plants has a heterotrophic
      constituent which could explain the presence of root-inhabiting microbes of
      unknown ecological function. Our discovery has implications for soil ecology and
      applications including future sustainable agriculture with efficient nutrient
      cycles.

PMID- 20689835
TI  - Two-week versus six-month sampling interval in a short-term natural history study
      of oral HPV infection in an HIV-positive cohort.
AB  - BACKGROUND: Oral HPV infections detected six-months apart were compared to those
      detected bi-weekly, in an HIV-positive cohort, during the intervening months to
      elucidate systematic biases introduced into natural history studies by sampling
      interval. METHODS: Fourteen consecutive oral rinse samples were collected every
      two weeks for six months from an HIV-positive cohort (n = 112) and evaluated for
      the presence of 37 HPV types. The cumulative probability of type-specific HPV
      detection at visits 1 through 14 was determined as a function of infection
      categorized at visits 1 and 14 as persistent, newly detected, cleared or absent.
      Transition models were used to evaluate the effect of HPV viral load (measured by
      RT-PCR for HPV 16, 18, 31, 33, 35) on infection persistence. RESULTS: The average
      point prevalence of oral HPV infection was similar at two-week and six-month
      sampling intervals (45% vs. 47%, p = 0.52), but cumulative prevalence was higher
      with the former (82% vs. 53%, p<0.001) as was the cumulative prevalence of type
      specific infections (9.3% vs 3.8%, p<0.0001). Type-specific infections persistent
      under a six-month sampling interval had a high probability (0.93, 95%CI 0.83
      0.98) of detection at 50% or more of the intervening visits and infections that
      were absent had a high probability (0.94, 95% CI 0.93-0.95) of no interval
      detection. The odds of detection at any visit significantly increased for each
      unit increase in HPV viral load at the previous visit. CONCLUSIONS: Six-month
      sampling is appropriate to model factors associated with type-specific oral HPV
      infection persistence but may misclassify HPV-exposed individuals as unexposed.

PMID- 20689834
TI  - Retinoic acids potentiate BMP9-induced osteogenic differentiation of mesenchymal
      progenitor cells.
AB  - BACKGROUND: As one of the least studied bone morphogenetic proteins (BMPs), BMP9
      is one of the most osteogenic BMPs. Retinoic acid (RA) signaling is known to play
      an important role in development, differentiation and bone metabolism. In this
      study, we investigate the effect of RA signaling on BMP9-induced osteogenic
      differentiation of mesenchymal progenitor cells (MPCs). METHODOLOGY/PRINCIPAL
      FINDINGS: Both primary MPCs and MPC line are used for BMP9 and RA stimulation.
      Recombinant adenoviruses are used to deliver BMP9, RARalpha and RXRalpha into
      MPCs. The in vitro osteogenic differentiation is monitored by determining the
      early and late osteogenic markers and matrix mineralization. Mouse perinatal limb
      explants and in vivo MPC implantation experiments are carried out to assess bone
      formation. We find that both 9CRA and ATRA effectively induce early osteogenic
      marker, such as alkaline phosphatase (ALP), and late osteogenic markers, such as
      osteopontin (OPN) and osteocalcin (OC). BMP9-induced osteogenic differentiation
      and mineralization is synergistically enhanced by 9CRA and ATRA in vitro. 9CRA
      and ATRA are shown to induce BMP9 expression and activate BMPR Smad-mediated
      transcription activity. Using mouse perinatal limb explants, we find that BMP9
      and RAs act together to promote the expansion of hypertrophic chondrocyte zone at
      growth plate. Progenitor cell implantation studies reveal that co-expression of
      BMP9 and RXRalpha or RARalpha significantly increases trabecular bone and osteoid
      matrix formation. CONCLUSION/SIGNIFICANCE: Our results strongly suggest that
      retinoid signaling may synergize with BMP9 activity in promoting osteogenic
      differentiation of MPCs. This knowledge should expand our understanding about how
      BMP9 cross-talks with other signaling pathways. Furthermore, a combination of
      BMP9 and retinoic acid (or its agonists) may be explored as effective bone
      regeneration therapeutics to treat large segmental bony defects, non-union
      fracture, and/or osteoporotic fracture.

PMID- 20689836
TI  - Breath formate is a marker of airway S-nitrosothiol depletion in severe asthma.
AB  - BACKGROUND: Children with severe asthma have poor symptom control and elevated
      markers of airway oxidative and nitrosative stress. Paradoxically, they have
      decreased airway levels of S-nitrosothiols (SNOs), a class of endogenous airway
      smooth muscle relaxants. This deficiency results from increased activity of an
      enzyme that both reduces SNOs to ammonia and oxidizes formaldehyde to formic
      acid, a volatile carboxylic acid that is more easily detected in exhaled breath
      condensate (EBC) than SNOs. We therefore hypothesize that depletion of airway
      SNOs is related to asthma pathology, and breath formate concentration may be a
      proxy measure of SNO catabolism. METHODS AND FINDINGS: We collected EBC samples
      from children and adolescents, including 38 with severe asthma, 46 with mild-to
      moderate asthma and 16 healthy adolescent controls, and the concentration of
      ionic constituents was quantified using ion chromatography. The concentrations of
      EBC components with volatile conjugates were log-normally distributed. Formate
      was the principal ion that displayed a significant difference between asthma
      status classifications. The mean EBC formate concentration was 40% higher in
      samples collected from all asthmatics than from healthy controls (mean = 5.7
      microM, mean+/-standard deviation = 3.1-10.3 microM vs. 4.0, 2.8-5.8 microM, p =
      0.05). EBC formate was higher in severe asthmatics than in mild-to-moderate
      asthmatics (6.8, 3.7-12.3 microM vs. 4.9, 2.8-8.7 microM, p = 0.012). In
      addition, formate concentration was negatively correlated with methacholine
      PC(20) (r = -0.39, p = 0.002, asthmatics only), and positively correlated with
      the NO-derived ion nitrite (r = 0.46, p<0.0001) as well as with total serum IgE
      (r = 0.28, p = 0.016, asthmatics only). Furthermore, formate was not
      significantly correlated with other volatile organic acids nor with inhaled
      corticosteroid dose. CONCLUSIONS: We conclude that EBC formate concentration is
      significantly higher in the breath of children with asthma than in those without
      asthma. In addition, amongst asthmatics, formate is elevated in the breath of
      those with severe asthma compared to those with mild-to-moderate asthma. We
      suggest that this difference is related to asthma pathology and may be a product
      of increased catabolism of endogenous S-nitrosothiols.

PMID- 20689840
TI  - Marine biodiversity in Japanese waters.
AB  - To understand marine biodiversity in Japanese waters, we have compiled
      information on the marine biota in Japanese waters, including the number of
      described species (species richness), the history of marine biology research in
      Japan, the state of knowledge, the number of endemic species, the number of
      identified but undescribed species, the number of known introduced species, and
      the number of taxonomic experts and identification guides, with consideration of
      the general ocean environmental background, such as the physical and geological
      settings. A total of 33,629 species have been reported to occur in Japanese
      waters. The state of knowledge was extremely variable, with taxa containing many
      inconspicuous, smaller species tending to be less well known. The total number of
      identified but undescribed species was at least 121,913. The total number of
      described species combined with the number of identified but undescribed species
      reached 155,542. This is the best estimate of the total number of species in
      Japanese waters and indicates that more than 70% of Japan's marine biodiversity
      remains un-described. The number of species reported as introduced into Japanese
      waters was 39. This is the first attempt to estimate species richness for all
      marine species in Japanese waters. Although its marine biota can be considered
      relatively well known, at least within the Asian-Pacific region, considering the
      vast number of different marine environments such as coral reefs, ocean trenches,
      ice-bound waters, methane seeps, and hydrothermal vents, much work remains to be
      done. We expect global change to have a tremendous impact on marine biodiversity
      and ecosystems. Japan is in a particularly suitable geographic situation and has
      a lot of facilities for conducting marine science research. Japan has an
      important responsibility to contribute to our understanding of life in the
      oceans.

PMID- 20689841
TI  - Antarctic marine biodiversity--what do we know about the distribution of life in
      the Southern Ocean?
AB  - The remote and hostile Southern Ocean is home to a diverse and rich community of
      life that thrives in an environment dominated by glaciations and strong currents.
      Marine biological studies in the region date back to the nineteenth century, but
      despite this long history of research, relatively little is known about the
      complex interactions between the highly seasonal physical environment and the
      species that inhabit the Southern Ocean. Oceanographically, the Southern Ocean is
      a major driver of global ocean circulation and plays a vital role in interacting
      with the deep water circulation in each of the Pacific, Atlantic, and Indian
      oceans. The Census of Antarctic Marine Life and the Scientific Committee on
      Antarctic Research Marine Biodiversity Information Network (SCAR-MarBIN) have
      strived to coordinate and unify the available scientific expertise and
      biodiversity data to improve our understanding of Southern Ocean biodiversity.
      Taxonomic lists for all marine species have been compiled to form the Register of
      Antarctic Marine Species, which currently includes over 8,200 species. SCAR
      MarBIN has brought together over 1 million distribution records for Southern
      Ocean species, forming a baseline against which future change can be judged. The
      sample locations and numbers of known species from different regions were mapped
      and the depth distributions of benthic samples plotted. Our knowledge of the
      biodiversity of the Southern Ocean is largely determined by the relative
      inaccessibility of the region. Benthic sampling is largely restricted to the
      shelf; little is known about the fauna of the deep sea. The location of
      scientific bases heavily influences the distribution pattern of sample and
      observation data, and the logistical supply routes are the focus of much of the
      at-sea and pelagic work. Taxa such as mollusks and echinoderms are well
      represented within existing datasets with high numbers of georeferenced records.
      Other taxa, including the species-rich nematodes, are represented by just a
      handful of digital records.

PMID- 20689842
TI  - Peroxidase profiling reveals genetic linkage between peroxidase gene clusters and
      basal host and non-host resistance to rusts and mildew in barley.
AB  - BACKGROUND: Higher plants possess a large multigene family encoding secreted
      class III peroxidase (Prx) proteins. Peroxidases appear to be associated with
      plant disease resistance based on observations of induction during disease
      challenge and the presence or absence of isozymes in resistant vs susceptible
      varieties. Despite these associations, there is no evidence that allelic
      variation of peroxidases directly determines levels of disease resistance.
      METHODOLOGY/PRINCIPAL FINDINGS: The current study introduces a new strategy
      called Prx-Profiling. We showed that with this strategy a large number of
      peroxidase genes can be mapped on the barley genome. In order to obtain an
      estimate of the total number of Prx clusters we followed a re-sampling procedure,
      which indicated that the barley genome contains about 40 peroxidase gene
      clusters. We examined the association between the Prxs mapped and the QTLs for
      resistance of barley to homologous and heterologous rusts, and to the barley
      powdery mildew fungus. We report that 61% of the QTLs for partial resistance to
      P. hordei, 61% of the QTLs for resistance to B. graminis and 47% of the QTLs for
      non-host resistance to other Puccinia species co-localize with Prx based markers.
      CONCLUSIONS/SIGNIFICANCE: We conclude that Prx-Profiling was effective in finding
      the genetic location of Prx genes on the barley genome. The finding that QTLs for
      basal resistance to rusts and powdery mildew fungi tend to co-locate with Prx
      clusters provides a base for exploring the functional role of Prx-related genes
      in determining natural differences in levels of basal resistance.

PMID- 20689843
TI  - Marine biodiversity and biogeography--regional comparisons of global issues, an
      introduction.

PMID- 20689845
TI  - Biodiversity's big wet secret: the global distribution of marine biological
      records reveals chronic under-exploration of the deep pelagic ocean.
AB  - BACKGROUND: Understanding the distribution of marine biodiversity is a crucial
      first step towards the effective and sustainable management of marine ecosystems.
      Recent efforts to collate location records from marine surveys enable us to
      assemble a global picture of recorded marine biodiversity. They also effectively
      highlight gaps in our knowledge of particular marine regions. In particular, the
      deep pelagic ocean--the largest biome on Earth--is chronically under-represented
      in global databases of marine biodiversity. METHODOLOGY/PRINCIPAL FINDINGS: We
      use data from the Ocean Biogeographic Information System to plot the position in
      the water column of ca 7 million records of marine species occurrences. Records
      from relatively shallow waters dominate this global picture of recorded marine
      biodiversity. In addition, standardising the number of records from regions of
      the ocean differing in depth reveals that regardless of ocean depth, most records
      come either from surface waters or the sea bed. Midwater biodiversity is
      drastically under-represented. CONCLUSIONS/SIGNIFICANCE: The deep pelagic ocean
      is the largest habitat by volume on Earth, yet it remains biodiversity's big wet
      secret, as it is hugely under-represented in global databases of marine
      biological records. Given both its value in the provision of a range of ecosystem
      services, and its vulnerability to threats including overfishing and climate
      change, there is a pressing need to increase our knowledge of Earth's largest
      ecosystem.

PMID- 20689844
TI  - The biodiversity of the Mediterranean Sea: estimates, patterns, and threats.
AB  - The Mediterranean Sea is a marine biodiversity hot spot. Here we combined an
      extensive literature analysis with expert opinions to update publicly available
      estimates of major taxa in this marine ecosystem and to revise and update several
      species lists. We also assessed overall spatial and temporal patterns of species
      diversity and identified major changes and threats. Our results listed
      approximately 17,000 marine species occurring in the Mediterranean Sea. However,
      our estimates of marine diversity are still incomplete as yet-undescribed species
      will be added in the future. Diversity for microbes is substantially
      underestimated, and the deep-sea areas and portions of the southern and eastern
      region are still poorly known. In addition, the invasion of alien species is a
      crucial factor that will continue to change the biodiversity of the
      Mediterranean, mainly in its eastern basin that can spread rapidly northwards and
      westwards due to the warming of the Mediterranean Sea. Spatial patterns showed a
      general decrease in biodiversity from northwestern to southeastern regions
      following a gradient of production, with some exceptions and caution due to gaps
      in our knowledge of the biota along the southern and eastern rims. Biodiversity
      was also generally higher in coastal areas and continental shelves, and decreases
      with depth. Temporal trends indicated that overexploitation and habitat loss have
      been the main human drivers of historical changes in biodiversity. At present,
      habitat loss and degradation, followed by fishing impacts, pollution, climate
      change, eutrophication, and the establishment of alien species are the most
      important threats and affect the greatest number of taxonomic groups. All these
      impacts are expected to grow in importance in the future, especially climate
      change and habitat degradation. The spatial identification of hot spots
      highlighted the ecological importance of most of the western Mediterranean
      shelves (and in particular, the Strait of Gibraltar and the adjacent Alboran
      Sea), western African coast, the Adriatic, and the Aegean Sea, which show high
      concentrations of endangered, threatened, or vulnerable species. The Levantine
      Basin, severely impacted by the invasion of species, is endangered as well. This
      abstract has been translated to other languages (File S1).

PMID- 20689846
TI  - Marine biodiversity of Aotearoa New Zealand.
AB  - The marine-biodiversity assessment of New Zealand (Aotearoa as known to Maori) is
      confined to the 200 nautical-mile boundary of the Exclusive Economic Zone, which,
      at 4.2 million km(2), is one of the largest in the world. It spans 30 degrees of
      latitude and includes a high diversity of seafloor relief, including a trench 10
      km deep. Much of this region remains unexplored biologically, especially the 50%
      of the EEZ deeper than 2,000 m. Knowledge of the marine biota is based on more
      than 200 years of marine exploration in the region. The major oceanographic data
      repository is the National Institute of Water and Atmospheric Research (NIWA),
      which is involved in several Census of Marine Life field projects and is the
      location of the Southwestern Pacific Regional OBIS Node; NIWA is also data
      manager and custodian for fisheries research data owned by the Ministry of
      Fisheries. Related data sources cover alien species, environmental measures, and
      historical information. Museum collections in New Zealand hold more than 800,000
      registered lots representing several million specimens. During the past decade,
      220 taxonomic specialists (85 marine) from 18 countries have been engaged in a
      project to review New Zealand's entire biodiversity. The above-mentioned marine
      information sources, published literature, and reports were scrutinized to give
      the results summarized here for the first time (current to 2010), including data
      on endemism and invasive species. There are 17,135 living species in the EEZ.
      This diversity includes 4,315 known undescribed species in collections. Species
      diversity for the most intensively studied phylum-level taxa (Porifera, Cnidaria,
      Mollusca, Brachiopoda, Bryozoa, Kinorhyncha, Echinodermata, Chordata) is more or
      less equivalent to that in the ERMS (European Register of Marine Species) region,
      which is 5.5 times larger in area than the New Zealand EEZ. The implication is
      that, when all other New Zealand phyla are equally well studied, total marine
      diversity in the EEZ may be expected to equal that in the ERMS region. This
      equivalence invites testable hypotheses to explain it. There are 177 naturalized
      alien species in New Zealand coastal waters, mostly in ports and harbours. Marine
      taxonomic expertise in New Zealand covers a broad number of taxa but is,
      proportionately, at or near its lowest level since the Second World War.
      Nevertheless, collections are well supported by funding and are continually added
      to. Threats and protection measures concerning New Zealand's marine biodiversity
      are commented on, along with potential and priorities for future research.

PMID- 20689847
TI  - Marine biodiversity in the Australian region.
AB  - The entire Australian marine jurisdictional area, including offshore and sub
      Antarctic islands, is considered in this paper. Most records, however, come from
      the Exclusive Economic Zone (EEZ) around the continent of Australia itself. The
      counts of species have been obtained from four primary databases (the Australian
      Faunal Directory, Codes for Australian Aquatic Biota, Online Zoological
      Collections of Australian Museums, and the Australian node of the Ocean
      Biogeographic Information System), but even these are an underestimate of
      described species. In addition, some partially completed databases for particular
      taxonomic groups, and specialized databases (for introduced and threatened
      species) have been used. Experts also provided estimates of the number of known
      species not yet in the major databases. For only some groups could we obtain an
      (expert opinion) estimate of undiscovered species. The databases provide patchy
      information about endemism, levels of threat, and introductions. We conclude that
      there are about 33,000 marine species (mainly animals) in the major databases, of
      which 130 are introduced, 58 listed as threatened and an unknown percentage
      endemic. An estimated 17,000 more named species are either known from the
      Australian EEZ but not in the present databases, or potentially occur there. It
      is crudely estimated that there may be as many as 250,000 species (known and yet
      to be discovered) in the Australian EEZ. For 17 higher taxa, there is sufficient
      detail for subdivision by Large Marine Domains, for comparison with other
      National and Regional Implementation Committees of the Census of Marine Life.
      Taxonomic expertise in Australia is unevenly distributed across taxa, and
      declining. Comments are given briefly on biodiversity management measures in
      Australia, including but not limited to marine protected areas.

PMID- 20689848
TI  - Deep-sea biodiversity in the Mediterranean Sea: the known, the unknown, and the
      unknowable.
AB  - Deep-sea ecosystems represent the largest biome of the global biosphere, but
      knowledge of their biodiversity is still scant. The Mediterranean basin has been
      proposed as a hot spot of terrestrial and coastal marine biodiversity but has
      been supposed to be impoverished of deep-sea species richness. We summarized all
      available information on benthic biodiversity (Prokaryotes, Foraminifera,
      Meiofauna, Macrofauna, and Megafauna) in different deep-sea ecosystems of the
      Mediterranean Sea (200 to more than 4,000 m depth), including open slopes, deep
      basins, canyons, cold seeps, seamounts, deep-water corals and deep-hypersaline
      anoxic basins and analyzed overall longitudinal and bathymetric patterns. We show
      that in contrast to what was expected from the sharp decrease in organic carbon
      fluxes and reduced faunal abundance, the deep-sea biodiversity of both the
      eastern and the western basins of the Mediterranean Sea is similarly high. All of
      the biodiversity components, except Bacteria and Archaea, displayed a decreasing
      pattern with increasing water depth, but to a different extent for each
      component. Unlike patterns observed for faunal abundance, highest negative values
      of the slopes of the biodiversity patterns were observed for Meiofauna, followed
      by Macrofauna and Megafauna. Comparison of the biodiversity associated with open
      slopes, deep basins, canyons, and deep-water corals showed that the deep basins
      were the least diverse. Rarefaction curves allowed us to estimate the expected
      number of species for each benthic component in different bathymetric ranges. A
      large fraction of exclusive species was associated with each specific habitat or
      ecosystem. Thus, each deep-sea ecosystem contributes significantly to overall
      biodiversity. From theoretical extrapolations we estimate that the overall deep
      sea Mediterranean biodiversity (excluding prokaryotes) reaches approximately 2805
      species of which about 66% is still undiscovered. Among the biotic components
      investigated (Prokaryotes excluded), most of the unknown species are within the
      phylum Nematoda, followed by Foraminifera, but an important fraction of
      macrofaunal and megafaunal species also remains unknown. Data reported here
      provide new insights into the patterns of biodiversity in the deep-sea
      Mediterranean and new clues for future investigations aimed at identifying the
      factors controlling and threatening deep-sea biodiversity.

PMID- 20689849
TI  - Marine biodiversity in South Africa: an evaluation of current states of
      knowledge.
AB  - Continental South Africa has a coastline of some 3,650 km and an Exclusive
      Economic Zone (EEZ) of just over 1 million km(2). Waters in the EEZ extend to a
      depth of 5,700 m, with more than 65% deeper than 2,000 m. Despite its status as a
      developing nation, South Africa has a relatively strong history of marine
      taxonomic research and maintains comprehensive and well-curated museum
      collections totaling over 291,000 records. Over 3 million locality records from
      more than 23,000 species have been lodged in the regional AfrOBIS (African Ocean
      Biogeographic Information System) data center (which stores data from a wider
      African region). A large number of regional guides to the marine fauna and flora
      are also available and are listed. The currently recorded marine biota of South
      Africa numbers at least 12,914 species, although many taxa, particularly those of
      small body size, remain poorly documented. The coastal zone is relatively well
      sampled with some 2,500 samples of benthic invertebrate communities have been
      taken by grab, dredge, or trawl. Almost none of these samples, however, were
      collected after 1980, and over 99% of existing samples are from depths shallower
      than 1,000 m--indeed 83% are from less than 100 m. The abyssal zone thus remains
      almost completely unexplored. South Africa has a fairly large industrial fishing
      industry, of which the largest fisheries are the pelagic (pilchard and anchovy)
      and demersal (hake) sectors, both focused on the west and south coasts. The east
      coast has fewer, smaller commercial fisheries, but a high coastal population
      density, resulting in intense exploitation of inshore resources by recreational
      and subsistence fishers, and this has resulted in the overexploitation of many
      coastal fish and invertebrate stocks. South Africa has a small aquaculture
      industry rearing mussels, oysters, prawns, and abalone-the latter two in land
      based facilities. Compared with many other developing countries, South Africa has
      a well-conserved coastline, 23% of which is under formal protection, however
      deeper waters are almost entirely excluded from conservation areas. Marine
      pollution is confined mainly to the densely populated KwaZulu-Natal coast and the
      urban centers of Cape Town and Port Elizabeth. Over 120 introduced or cryptogenic
      marine species have been recorded, but most of these are confined to the few
      harbors and sheltered sites along the coast.

PMID- 20689850
TI  - A census of marine biodiversity knowledge, resources, and future challenges.

PMID- 20689851
TI  - A Bayesian outlier criterion to detect SNPs under selection in large data sets.
AB  - BACKGROUND: The recent advent of high-throughput SNP genotyping technologies has
      opened new avenues of research for population genetics. In particular, a growing
      interest in the identification of footprints of selection, based on genome scans
      for adaptive differentiation, has emerged. METHODOLOGY/PRINCIPAL FINDINGS: The
      purpose of this study is to develop an efficient model-based approach to perform
      bayesian exploratory analyses for adaptive differentiation in very large SNP data
      sets. The basic idea is to start with a very simple model for neutral loci that
      is easy to implement under a bayesian framework and to identify selected loci as
      outliers via Posterior Predictive P-values (PPP-values). Applications of this
      strategy are considered using two different statistical models. The first one was
      initially interpreted in the context of populations evolving respectively under
      pure genetic drift from a common ancestral population while the second one relies
      on populations under migration-drift equilibrium. Robustness and power of the two
      resulting bayesian model-based approaches to detect SNP under selection are
      further evaluated through extensive simulations. An application to a cattle data
      set is also provided. CONCLUSIONS/SIGNIFICANCE: The procedure described turns out
      to be much faster than former bayesian approaches and also reasonably efficient
      especially to detect loci under positive selection.

PMID- 20689852
TI  - An overview of marine biodiversity in United States waters.
AB  - Marine biodiversity of the United States (U.S.) is extensively documented, but
      data assembled by the United States National Committee for the Census of Marine
      Life demonstrate that even the most complete taxonomic inventories are based on
      records scattered in space and time. The best-known taxa are those of commercial
      importance. Body size is directly correlated with knowledge of a species, and
      knowledge also diminishes with distance from shore and depth. Measures of
      biodiversity other than species diversity, such as ecosystem and genetic
      diversity, are poorly documented. Threats to marine biodiversity in the U.S. are
      the same as those for most of the world: overexploitation of living resources;
      reduced water quality; coastal development; shipping; invasive species; rising
      temperature and concentrations of carbon dioxide in the surface ocean, and other
      changes that may be consequences of global change, including shifting currents;
      increased number and size of hypoxic or anoxic areas; and increased number and
      duration of harmful algal blooms. More information must be obtained through field
      and laboratory research and monitoring that involve innovative sampling
      techniques (such as genetics and acoustics), but data that already exist must be
      made accessible. And all data must have a temporal component so trends can be
      identified. As data are compiled, techniques must be developed to make certain
      that scales are compatible, to combine and reconcile data collected for various
      purposes with disparate gear, and to automate taxonomic changes. Information on
      biotic and abiotic elements of the environment must be interactively linked.
      Impediments to assembling existing data and collecting new data on marine
      biodiversity include logistical problems as well as shortages in finances and
      taxonomic expertise.

PMID- 20689853
TI  - Assessment of the quality of reporting in abstracts of randomized controlled
      trials published in five leading Chinese medical journals.
AB  - BACKGROUND: Clear, transparent and sufficiently detailed abstracts of randomized
      trials (RCTs), published in journal articles are important because readers will
      often base their initial assessment of a trial on such information. However,
      little is known about the quality of reporting in abstracts of RCTs published in
      medical journals in China. METHODS: We identified RCTs abstracts from 5 five
      leading Chinese medical journals published between 1998 and 2007 and indexed in
      MEDLINE. We assessed the quality of reporting of these abstracts based on the
      Consolidated Standards of Reporting Trials (CONSORT) abstract checklist. We also
      sought to identify whether any differences exist in reporting between the Chinese
      and English language version of the same abstract. RESULTS: We identified 332 RCT
      abstracts eligible for examination. Overall, the abstracts we examined reported 0
      8 items as designated in the CONSORT checklist. On average, three items were
      reported per abstract. Details of the interventions (288/332; 87%), the number of
      participants randomized (216/332; 65%) and study objectives (109/332; 33%) were
      the top three items reported. Only two RCT abstracts reported details of trial
      registration, no abstracts reported the method of allocation concealment and only
      one mentioned specifically who was blinded. In terms of the proportion of RCT
      abstracts fulfilling a criterion, the absolute difference (percentage points)
      between the Chinese and English abstracts was 10% (ranging from 0 to 25%) on
      average, per item. CONCLUSIONS: The quality of reporting in abstracts of RCTs
      published in Chinese medical journals needs to be improved. We hope that the
      introduction and endorsement of the CONSORT for Abstracts guidelines by journals
      reporting RCTs will lead to improvements in the quality of reporting.

PMID- 20689854
TI  - Conservation of forest birds: evidence of a shifting baseline in community
      structure.
AB  - BACKGROUND: Quantifying changes in forest bird diversity is an essential task for
      developing effective conservation actions. When subtle changes in diversity
      accumulate over time, annual comparisons may offer an incomplete perspective of
      changes in diversity. In this case, progressive change, the comparison of changes
      in diversity from a baseline condition, may offer greater insight because changes
      in diversity are assessed over longer periods of times. Our objectives were to
      determine how forest bird diversity has changed over time and whether those
      changes were associated with forest disturbance. METHODOLOGY/PRINCIPAL FINDINGS:
      We used North American Breeding Bird Survey data, a time series of Landsat images
      classified with respect to land cover change, and mixed-effects models to
      associate changes in forest bird community structure with forest disturbance,
      latitude, and longitude in the conterminous United States for the years 1985 to
      2006. We document a significant divergence from the baseline structure for all
      birds of similar migratory habit and nest location, and all forest birds as a
      group from 1985 to 2006. Unexpectedly, decreases in progressive similarity
      resulted from small changes in richness (<1 species per route for the 22-year
      study period) and modest losses in abundance (-28.7 - -10.2 individuals per
      route) that varied by migratory habit and nest location. Forest disturbance
      increased progressive similarity for Neotropical migrants, permanent residents,
      ground nesting, and cavity nesting species. We also documented highest
      progressive similarity in the eastern United States. CONCLUSIONS/SIGNIFICANCE:
      Contemporary forest bird community structure is changing rapidly over a
      relatively short period of time (e.g., approximately 22 years). Forest
      disturbance and forest regeneration are primary factors associated with
      contemporary forest bird community structure, longitude and latitude are
      secondary factors, and forest loss is a tertiary factor. Importantly, these
      findings suggest some regions of the United States may already fall below the
      habitat amount threshold where fragmentation effects become important predictors
      of forest bird community structure.

PMID- 20689855
TI  - Monocyte-derived dendritic cells exhibit increased levels of lysosomal
      proteolysis as compared to other human dendritic cell populations.
AB  - BACKGROUND: Fine control of lysosomal degradation for limited processing of
      internalized antigens is a hallmark of professional antigen presenting cells.
      Previous work in mice has shown that dendritic cells (DCs) contain lysosomes with
      remarkably low protease content. Combined with the ability to modulate lysosomal
      pH during phagocytosis and maturation, murine DCs enhance their production of
      class II MHC-peptide complexes for presentation to T cells. METHODOLOGY/PRINCIPAL
      FINDINGS: In this study we extend these findings to human DCs and distinguish
      between different subsets of DCs based on their ability to preserve internalized
      antigen. Whereas DCs derived in vitro from CD34+ hematopoietic progenitor cells
      or isolated from peripheral blood of healthy donors are protease poor, DCs
      derived in vitro from monocytes (MDDCs) are more similar to macrophages (M Phis)
      in protease content. Unlike other DCs, MDDCs also fail to reduce their
      intralysosomal pH in response to maturation stimuli. Indeed, functional
      characterization of lysosomal proteolysis indicates that MDDCs are comparable to
      M Phis in the rapid degradation of antigen while other human DC subtypes are
      attenuated in this capacity. CONCLUSIONS/SIGNIFICANCE: Human DCs are comparable
      to murine DCs in exhibiting a markedly reduced level of lysosomal proteolysis.
      However, as an important exception to this, human MDDCs stand apart from all
      other DCs by a heightened capacity for proteolysis that resembles that of M Phis.
      Thus, caution should be exercised when using human MDDCs as a model for DC
      function and cell biology.

PMID- 20689856
TI  - Marine biodiversity in the Caribbean: regional estimates and distribution
      patterns.
AB  - This paper provides an analysis of the distribution patterns of marine
      biodiversity and summarizes the major activities of the Census of Marine Life
      program in the Caribbean region. The coastal Caribbean region is a large marine
      ecosystem (LME) characterized by coral reefs, mangroves, and seagrasses, but
      including other environments, such as sandy beaches and rocky shores. These
      tropical ecosystems incorporate a high diversity of associated flora and fauna,
      and the nations that border the Caribbean collectively encompass a major global
      marine biodiversity hot spot. We analyze the state of knowledge of marine
      biodiversity based on the geographic distribution of georeferenced species
      records and regional taxonomic lists. A total of 12,046 marine species are
      reported in this paper for the Caribbean region. These include representatives
      from 31 animal phyla, two plant phyla, one group of Chromista, and three groups
      of Protoctista. Sampling effort has been greatest in shallow, nearshore waters,
      where there is relatively good coverage of species records; offshore and deep
      environments have been less studied. Additionally, we found that the currently
      accepted classification of marine ecoregions of the Caribbean did not apply for
      the benthic distributions of five relatively well known taxonomic groups. Coastal
      species richness tends to concentrate along the Antillean arc (Cuba to the
      southernmost Antilles) and the northern coast of South America (Venezuela
      Colombia), while no pattern can be observed in the deep sea with the available
      data. Several factors make it impossible to determine the extent to which these
      distribution patterns accurately reflect the true situation for marine
      biodiversity in general: (1) highly localized concentrations of collecting effort
      and a lack of collecting in many areas and ecosystems, (2) high variability among
      collecting methods, (3) limited taxonomic expertise for many groups, and (4)
      differing levels of activity in the study of different taxa.

PMID- 20689857
TI  - Global analyses of small interfering RNAs derived from Bamboo mosaic virus and
      its associated satellite RNAs in different plants.
AB  - BACKGROUND: Satellite RNAs (satRNAs), virus parasites, are exclusively associated
      with plant virus infection and have attracted much interest over the last 3
      decades. Upon virus infection, virus-specific small interfering RNAs (vsiRNAs)
      are produced by dicer-like (DCL) endoribonucleases for anti-viral defense. The
      composition of vsiRNAs has been studied extensively; however, studies of satRNA
      derived siRNAs (satsiRNAs) or siRNA profiles after satRNA co-infection are
      limited. Here, we report on the small RNA profiles associated with infection with
      Bamboo mosaic virus (BaMV) and its two satellite RNAs (satBaMVs) in Nicotiana
      benthamiana and Arabidopsis thaliana. METHODOLOGY/PRINCIPAL FINDINGS: Leaves of
      N. benthamiana or A. thaliana inoculated with water, BaMV alone or co-inoculated
      with interfering or noninterfering satBaMV were collected for RNA extraction,
      then large-scale Solexa sequencing. Up to about 20% of total siRNAs as BaMV
      specific siRNAs were accumulated in highly susceptible N. benthamiana leaves
      inoculated with BaMV alone or co-inoculated with noninterfering satBaMV; however,
      only about 0.1% of vsiRNAs were produced in plants co-infected with interfering
      satBaMV. The abundant region of siRNA distribution along BaMV and satBaMV genomes
      differed by host but not by co-infection with satBaMV. Most of the BaMV and
      satBaMV siRNAs were 21 or 22 nt, of both (+) and (-) polarities; however, a
      higher proportion of 22-nt BaMV and satBaMV siRNAs were generated in N.
      benthamiana than in A. thaliana. Furthermore, the proportion of non-viral 24-nt
      siRNAs was greatly increased in N. benthamiana after virus infection.
      CONCLUSIONS/SIGNIFICANCE: The overall composition of vsiRNAs and satsiRNAs in the
      infected plants reflect the combined action of virus, satRNA and different DCLs
      in host plants. Our findings suggest that the structure and/or sequence demands
      of various DCLs in different hosts may result in differential susceptibility to
      the same virus. DCL2 producing 24-nt siRNAs under biotic stresses may play a
      vital role in the antiviral mechanism in N. benthamiana.

PMID- 20689859
TI  - Assessing strategy and equity in the elimination of malaria.

PMID- 20689858
TI  - Glypican-1, phosphacan/receptor protein-tyrosine phosphatase-zeta/beta and its
      ligand, tenascin-C, are expressed by neural stem cells and neural cells derived
      from embryonic stem cells.
AB  - The heparan sulfate proteoglycan glypican-1, the chondroitin sulfate proteoglycan
      phosphacan/RPTP (receptor protein-tyrosine phosphatase)-zeta/beta and the
      extracellular matrix protein tenascin-C were all found to be expressed by neural
      stem cells and by neural cells derived from them. Expression of proteoglycans and
      tenascin-C increased after retinoic acid induction of SSEA1-positive ES
      (embryonic stem) cells to nestin-positive neural stem cells, and after neural
      differentiation, proteoglycans and tenascin-C are expressed by both neurons and
      astrocytes, where they surround cell bodies and processes and in certain cases
      show distinctive expression patterns. With the exception of tenascin-C (whose
      expression may decrease somewhat), expression levels do not change noticeably
      during the following 2 weeks in culture. The significant expression, by neural
      stem cells and neurons and astrocytes derived from them, of two major heparan
      sulfate and chondroitin sulfate proteoglycans of nervous tissue and of tenascin
      C, a high-affinity ligand of phosphacan/RPTP-zeta/beta, indicates that an
      understanding of their specific functional roles in stem cell neurobiology will
      be important for the therapeutic application of this new technology in
      facilitating nervous tissue repair and regeneration.

PMID- 20689860
TI  - Light induced stimulation and delay of cardiac activity.
AB  - This article shows the combination of light activatable ion channels and
      microelectrode array (MEA) technology for bidirectionally interfacing cells. HL-1
      cultures, a mouse derived cardiomyocyte-like cell line, transfected with
      channelrhodopsin were stimulated with a microscope coupled 473 nm laser and
      recorded with custom built 64 electrode MEAs. Channelrhodopsin induced
      depolarization of the cell can evoke action potentials (APs) in single cells.
      Spreading of the AP over the cell layer can then be measured with good
      spatiotemporal resolution using MEA recordings. The possibility for light induced
      pacemaker switching in cultures was shown. Furthermore, the suppression of APs
      can also be achieved with the laser. Possible applications include cell analysis,
      e.g. pacemaker interference or induced pacemaker switching, and medical
      applications such as a combined cardiac pacemaker and defibrillator triggered by
      light. Since current prosthesis research focuses on bidirectionality, this system
      may be applied to any electrogenic cell, including neurons or muscles, to advance
      this field.

PMID- 20689861
TI  - Enhanced mobile hybridization of gold nanoparticles decorated with
      oligonucleotide in microchannel devices.
AB  - Mobile hybridization is a concept proposed and verified herein. We have designed
      a microfluidic device that is capable of enhancing passive mixing through the
      morphology of micro-structures, positioned along the channels of the device. We
      investigated the capability of these structures to promote mobile hybridization
      of fluorophore-labeled target oligonucleotides to oligonucleotide gold
      nanoparticle (Au-NP) probes. This process is monitored with fluorescence through
      the quenching of the fluorescent signal within the device as the target
      oligonucleotides become bound to the Au-NP probes. We evaluated the fluorescent
      intensity of a sample image that showed enhanced probability of mobile
      hybridization of the samples, which was completed in about 7.2 s. Mobile
      hybridization is thus much more effective than traditional static hybridization
      (reaction overnight) limited by molecular diffusion. This approach promises an
      improved hybridization of samples with these probes, and is beneficial for
      microfluidic-based systems for biomedical detection.

PMID- 20689862
TI  - Precise control over the oxygen conditions within the Boyden chamber using a
      microfabricated insert.
AB  - Cell migration is a hallmark of cancer cell metastasis and is highly correlated
      with hypoxia in tumors. The Boyden chamber is a porous membrane-based migration
      platform that has seen a great deal of use for both in vitro migration and
      invasion assays due to its adaptability to common culture vessels and relative
      ease of use. The hypoxic chamber is a current tool that can be implemented to
      investigate the cellular response to oxygen paradigms. Unfortunately, this method
      lacks the spatial and temporal precision to accurately model a number of
      physiological phenomena. In this article, we present a newly developed
      microfabricated polydimethylsiloxane (PDMS) device that easily adapts to the
      Boyden chamber, and provides more control over the oxygenation conditions exposed
      to cells. The device equilibrates to 1% oxygen in about 20 min, thus
      demonstrating the capabilities of a system for researchers to establish both
      short-term continuous and intermittent hypoxia regimes. A Parylene-C thin-film
      coating was used to prevent ambient air penetration through the bulk PDMS and was
      found to yield improved equilibration times and end-point concentrations. MDA-MD
      231 cells, an invasive breast cancer line, were used as a model cell type to
      demonstrate the effect of oxygen concentration on cell migration through the
      Boyden chamber porous membrane. Continuous hypoxia downregulated migration of
      cells relative to the normoxic control, as did an intermittent hypoxia regime
      (IH) cycling between 0% and 21% oxygen (0-21% IH). However, cells exposed to 5
      21% IH exhibited increased migration compared to the other conditions, as well as
      relative to the normoxic control. The results presented here show the device can
      be utilized for experiments implementing the Boyden chamber for in vitro hypoxic
      studies, allowing experiments to be conducted faster and with more precision than
      currently possible.

PMID- 20689863
TI  - Multi-dimensional transition-metal coordination polymers with 5-nitro-1,2,3
      benzenetricarboxylic acid exhibiting ferro-/antiferromagnetic interactions.
AB  - Six transition metal coordination polymers, [Cu(3)(nbta)(2)(bipy)(2)(H(2)O)(2)] x
      2 H(2)O (1), [Cu(3)(nbta)(2)(bpp)(2)(H(2)O)(2)] x 2 H(2)O (2),
      [Co(3)(nbta)(2)(bipy)(3)(H(2)O)(2)] x 2 H(2)O (3),
      [Co(3)(nbta)(2)(bpp)(2)(H(2)O)(2)] (4), [Ni(2)(Hnbta)(2)(bipy)(2)(H(2)O)(2)] (5)
      and [Ni(3)(nbta)(2)(bpa)(3)(H(2)O)(2)] x 2 H(2)O (6) (H(3)nbta = 5-nitro-1,2,3
      benzenetricarboxylic acid, bipy = 4,4'-bipyridine, bpa = 1,2-bis(4
      pyridyl)ethane, bpp = 1,3-bis(4-pyridyl)propane), have been hydrothermally
      synthesized by the reactions of Cu(II), Co(II) and Ni(II) salts with H(3)nbta in
      the presence of dipyridyl-type co-ligands, respectively. Their structures were
      determined by single-crystal X-ray diffraction analyses and further characterized
      by elemental analyses, IR spectra, and TG analyses. Compounds 1-4 and 6 exhibit
      3D pillared-layer structures while compound 5 has a 2D layer. The nbta(3-)
      ligands in the 2D carboxylate layer motifs of 1-4 and 6 connect transition metal
      ions in different coordination modes, and the dipyridyl-type co-ligands in
      compounds 1-4 and 6 serve as the pillar between the 2D layers, creating 3D open
      frameworks. From a topologic point of view, complex 1, 2 and 4 present 4
      connected 3D coordination frameworks with the topologies of (4(2) x 6(2) x 8(2))
      (6(2) x 7(2) x 8(2)) (4(2) x 6(2) x 7 x 8), (6(4) x 8(2)) (4(2) x 6(4)) (4(2) x
      6(4)) and (4 x 6(4) x 8)(4(4) x 6(2))(4(3) x 6(3)) respectively. Complex 3 shows
      a (4,5)-connected 3D network with (4(2) x 6(7) x 8)(6(4) x 8(2))(4(2) x 6(4))
      topology. Whereas the structure of 5 is a 2D (4,4) net due to the partially
      deprotonated H(3)nbta ligand existed. Complex 6 features a 3D (4,5)-connected
      framework with (4 x 6(8) x 8) (6(5) x 8) (4 x 6(5)) topology, also exhibiting the
      intriguing helical motif. The variable-temperature magnetic susceptibility
      studies reveal antiferromagnetic interactions between Cu(II) or Co(II) ions in 1,
      2, 3, 4 and ferromagnetic interactions between Ni(II) ions for 5 and 6,
      respectively.

PMID- 20689864
TI  - Deformability based cell margination--a simple microfluidic design for malaria
      infected erythrocyte separation.
AB  - In blood vessels with luminal diameter less than 300 um, red blood cells (RBCs)
      which are smaller in size and more deformable than leukocytes, migrate to the
      axial centre of the vessel due to flow velocity gradient within the vessels. This
      phenomenon displaces the leukocytes to the vessel wall and is aptly termed as
      margination. Here, we demonstrate using microfluidics that stiffer malaria
      infected RBCs (iRBCs) behave similar to leukocytes and undergo margination
      towards the sidewalls. This provides better understanding of the hemodynamic
      effects of iRBCs in microcirculation and its contribution to pathophysiological
      outcome relating to cytoadherence to endothelium. In this work, cell margination
      is mimicked for the separation of iRBCs from whole blood based on their reduced
      deformability. The malaria infected sample was tested in a simple long straight
      channel microfluidic device fabricated in polydimethylsiloxane. In this
      microchannel, cell margination was directed along the channel width with the
      iRBCs aligning near each sidewall and then subsequently removed using a 3-outlet
      system, thus achieving separation. Tests were conducted using ring stage and late
      trophozoite/schizont stage iRBCs. Device performance was quantified by analyzing
      the distribution of these iRBCs across the microchannel width at the outlet and
      also conducting flow cytometry analysis. Results indicate recovery of
      approximately 75% for early stage iRBCs and >90% for late stage iRBCs at the side
      outlets. The simple and passive system operation makes this technique ideal for
      on-site iRBCs enrichment in resource-limited settings, and can be applied to
      other blood cell diseases, e.g. sickle cell anemia and leukemia, characterized by
      changes in cell stiffness.

PMID- 20689865
TI  - Wax-bonding 3D microfluidic chips.
AB  - We report a simple, low-cost and detachable microfluidic chip incorporating
      easily accessible paper, glass slides or other polymer films as the chip
      materials along with adhesive wax as the recycling bonding material. We use a
      laser to cut through the paper or film to form patterns and then sandwich the
      paper and film between glass sheets or polymer membranes. The hot-melt adhesive
      wax can realize bridge bonding between various materials, for example, paper,
      polymethylmethacrylate (PMMA) film, glass sheets, or metal plate. The bonding
      process is reversible and the wax is reusable through a melting and cooling
      process. With this process, a three-dimensional (3D) microfluidic chip is
      achievable by vacuating and venting the chip in a hot-water bath. To study the
      biocompatibility and applicability of the wax-based microfluidic chip, we tested
      the PCR compatibility with the chip materials first. Then we applied the wax
      paper based microfluidic chip to HeLa cell electroporation (EP). Subsequently, a
      prototype of a 5-layer 3D chip was fabricated by multilayer wax bonding. To check
      the sealing ability and the durability of the chip, green fluorescence protein
      (GFP) recombinant Escherichia coli (E. coli) bacteria were cultured, with which
      the chemotaxis of E. coli was studied in order to determine the influence of
      antibiotic ciprofloxacin concentration on the E. coli migration.

PMID- 20689866
TI  - Preparation of anti-Sudan red monoclonal antibody and development of an indirect
      competitive enzyme-linked immunosorbent assay for detection of Sudan red in
      chilli jam and chilli oil.
AB  - Sudan dyes are banned to be used in food additives because of the carcinogenicity
      of their metabolites. A rapid and sensitive indirect competitive enzyme-linked
      immunosorbent assay (ELISA) was developed to detect the residues of Sudan dyes.
      Novel immunogen and coating antigen were synthesized via glutaraldehyde linking.
      The hapten-bovine serum albumin (BSA) was applied as immunogen and the hapten
      ovalbumin (OVA) was served as coating antigen. The monoclonal antibody obtained
      showed high sensitivity to Sudan I with an IC(50) value of 1.7 MUg L(-1) in
      buffer and was suitable to detect the residues of Sudan red in food products. The
      specificity of the assay was studied by measuring cross-reactivity of the
      antibody with the structurally related compounds of Sudan II (<1%), Sudan IV
      (<1%) and para red (120%). Chilli jam and chilli oil samples spiked with Sudan
      dyes were analyzed by the method. The detection limit (LOD) of the ELISA method
      applied in chilli jam and chilli oil was 9.0 MUg L(-1) and 19.6 MUg L(-1),
      respectively. The recovery rates of Sudan-I in chilli oil and chilli jam were in
      the range of 80%-110% with coefficients of variation <25%. The intra-assay
      variation and inter-assay variation in buffer were both <9%.

PMID- 20689867
TI  - Damage to fuel cell membranes. Reaction of HO* with an oligomer of poly(sodium
      styrene sulfonate) and subsequent reaction with O(2).
AB  - An understanding of the reactivity of oligomeric compounds that model fuel cell
      membrane materials under oxidative-stress conditions that mimic the fuel cell
      operating environment can identify material weaknesses and yield valuable
      insights into how a polymer might be modified to improve oxidative stability. The
      reaction of HO radicals with a polymer electrolyte fuel cell membrane represents
      an initiation step for irreversible membrane oxidation. By means of pulse
      radiolysis, we measured k = (9.5 +/- 0.6) * 10(9) M(-1) s(-1) for the reaction of
      HO with poly(sodium styrene sulfonate), PSSS, with an average molecular weight of
      1100 Da (PSSS-1100) in aqueous solution at room temperature. In the initial
      reaction of HO with the oligomer (90 +/- 10)% react by addition to form
      hydroxycyclohexadienyl radicals, while the remaining abstract a hydrogen to yield
      benzyl radicals. The hydroxycyclohexadienyl radicals react reversibly with
      dioxygen to form the corresponding peroxyl radicals; the second-order rate
      constant for the forward reaction is k(f) = (3.0 +/- 0.5) * 10(7) M(-1) s(-1),
      and for the back reaction, we derive an upper limit for the rate constant k(r) of
      (4.5 +/- 0.9) * 10(3) s(-1). These data place a lower bound on the equilibrium
      constant K of (7 +/- 2) * 10(3) M(-1) at 295 K, which allows us to calculate a
      lower limit of the Gibbs energy for the reaction, (-21.7 +/- 0.8) kJ mol(-1). At
      pH 1, the hydroxycyclohexadienyl radicals decay with an overall first-order rate
      constant k of (6 +/- 1) * 10(3) s(-1) to yield benzyl radicals. The second-order
      rate constant for reaction of dioxygen with benzyl radicals of PSSS-1100 is k =
      (2-5) * 10(8) M(-1) s(-1). We discuss hydrogen abstraction from PSSS-1100 in
      terms of the bond dissociation energy, and relate these to relevant electrode
      potentials. We propose a reaction mechanism for the decay of
      hydroxycyclohexadienyl radicals and subsequent reaction steps.

PMID- 20689868
TI  - Tris(2-dimethylaminoethyl)amine: a simple new tripodal polyamine ligand for Group
      1 metals.
AB  - The first examples of Group 1 metal complexes of tris(2-dimethylaminoethyl)amine
      (Me(6)TREN) are reported including monomeric sodium complexes containing eta(4)
      bound ligands, suggesting their potential use in alkali-metal-mediated synthetic
      applications.

PMID- 20689869
TI  - A silicon nanowire-based electrochemical glucose biosensor with high
      electrocatalytic activity and sensitivity.
AB  - An electrochemical glucose biosensor was developed by immobilizing glucose
      oxidase (GOx) on an electrode decorated with a novel nanostructure, silicon
      nanowires (SiNWs) with in situ grown gold nanoparticles (AuNPs). The immobilized
      GOx displayed a pair of well-defined and quasi-reversible redox peaks with a
      formal potential (E(o ')) of -0.376 V in a phosphate buffer solution. The
      fabricated glucose biosensor has good electrocatalytic activity toward oxidation
      of glucose. In addition, such resultant SiNWs-based glucose biosensor possesses
      high biological affinity. Particularly, the apparent Michaelis-Mentan constant
      was estimated to be 0.902 mM, which is much smaller than the reported values for
      GOx at a range of nanomaterials-incorporated electrodes. Consequently, this novel
      SiNWs-based biosensor is expected to be a promising tool for biological assays
      (e.g., monitoring blood glucose).

PMID- 20689870
TI  - Gas-phase phenol methylation over Mg/Me/O (Me = Al, Cr, Fe) catalysts:
      mechanistic implications due to different acid-base and dehydrogenating
      properties.
AB  - This contribution reports about an in situ FT-IR investigation and the catalytic
      reactivity of Mg/Me(3+) mixed oxides (Me = Cr, Fe, or Al; Mg/Me = 2, atomic
      ratio) in the gas-phase methylation of phenol with methanol. It is the second of
      two papers concerning the mentioned systems, and its purpose is twofold: to
      confute the classic and not accurate theory concerning the reaction mechanism,
      and to propose a novel interpretation based on the combined use of catalytic
      tests and in situ molecular spectroscopy. Results here reported highlight that:
      (i) the reaction mechanism in phenol methylation, when catalysed by basic
      systems, is not a classical electrophylic substitution, as generally reported in
      the literature, but proceeds through the formation of formaldehyde as an
      intermediate, and (ii) the catalytic behaviour in respect to both methanol and
      phenol reactants is strictly dependent on catalyst features. Although all
      investigated systems exhibit a basic-type behaviour with regard to phenol, which
      dissociates to yield an adsorbed phenolate species, the distribution of phenolic
      compounds obtained with the Mg/Al/O catalyst was that typically observed with
      acid catalysts, with prevailing formation of anisole when the reaction was
      carried out below 350 degrees C and of mono and poly-C-alkylated compounds when
      the reaction temperature was above 350 degrees C. On the contrary, the reactivity
      shown by both Mg/Fe/O and Mg/Cr/O systems was that reported in the literature as
      typical of mixed oxides possessing basic features. The extent of methanol
      decomposition into light compounds was maximum in the case of Mg/Fe/O catalysts,
      because of the pronounced redox behaviour typical of Fe(3+) species, whereas
      neither methanol dehydrogenation nor decomposition were ever observed with
      Mg/Al/O up to 400 degrees C. Reactivity tests and spectroscopic experiments
      hinted for methanol dehydrogenation to formaldehyde as the first step in the ring
      methylation of phenol with Mg/Cr/O and Mg/Fe/O: in that case, o-cresol and 2,6
      xylenol were the only reaction products. But, with Mg/Al/O systems, for which no
      methanol dehydrogenation occurred, the formation of anisole was due to the
      synergistic effect of stronger basic features and the presence of Lewis acidic
      sites, that facilitate the reaction between phenol and methanol after activation
      over the two different types of catalytic sites.

PMID- 20689871
TI  - Integration in a multilayer microfluidic chip of 8 parallel cell sorters with
      flow control by sol-gel transition of thermoreversible gelation polymer.
AB  - Microfluidic systems have significant implications in the field of cell
      separation since they could provide platforms with inexpensive, disposable and
      sterile structures. Here, we present a novel strategy to integrate microfluidic
      sorters into a single chip for high throughput sorting. Our parallel sorter
      consists of a microfluidic chip with a three-dimensional channel network that
      utilizes flow switching by a heat-induced sol-gel transition of thermoreversible
      gelation polymer. The 8 parallel sheathed sample flows were realized by injecting
      sample and buffer solutions into only 2 inlets. The sheathed flows enabled
      disposal of unwanted sample waste without laser irradiation, and collection of
      wanted sample upon irradiation. As an application of the sorter, two kinds of
      fluorescent microspheres were separated with recovery ratio and purity of 70% or
      90% at throughputs of about 100 or 20 particles per second, respectively. Next,
      Escherichia coli cells expressing green fluorescent protein were separated from
      those expressing DsRed with recovery ratio and purity of 90% at a throughput of
      about 20 cells per second.

PMID- 20689872
TI  - Salt concentration-induced dehybridisation of DNA-gold nanoparticle conjugate
      assemblies for diagnostic applications.
AB  - We present the cooperative dehybridisation of DNA-gold nanoparticle conjugate
      (DNA-AuNP) assemblies induced by reduced salt concentration ([salt]), which can
      be precisely controlled by various conditions. The detection of Ag(+) based upon
      the [salt]-induced dehybridisation of DNA-AuNP assemblies is five times more
      sensitive than that achieved under conventional thermal melting conditions.

PMID- 20689873
TI  - Supramolecular dendrimer capsules by cooperative binding.
AB  - We exploit the unique features of dendrimers as molecular nanospheres with many
      peripheral binding sites to show that maximizing cooperative binding enables a
      novel modular self-assembly approach to construct supramolecular capsules.

PMID- 20689874
TI  - Reorganization energies and pre-exponential factors in the one-electron
      electrochemical and homogeneous oxidation of phenols coupled with an
      intramolecular amine-driven proton transfer.
AB  - Temperature variations of the kinetics of the electrochemical and homogeneous
      oxidation of the title compounds give rise to Arrhenius plots, the slopes of
      which give access to the heavy-atom (including solvent) reorganization energies.
      Information on the role of proton transfer in the dynamics of the concerted
      proton-electron transfer reaction (CPET) is potentially contained in the pre
      exponential factor. Previous analyses of the problem were based on equalling the
      pre-exponential factor in the absence of barrier for proton transfer with the
      collision frequency. Taking into account that the reaction may take place at
      various distances from the electrode surface increases the value of this limiting
      pre-exponential factor. Strategies are discussed for evaluating the impact of
      proton transfer in the CPET kinetics by comparing the experimental pre
      exponential factor with pre-exponential factors characterizing simple outersphere
      electron transfers.

PMID- 20689875
TI  - ZnS nano-architectures: photocatalysis, deactivation and regeneration.
AB  - An "infinite recycling" method for enhancing the durable applications of a ZnS
      nano-photocatalyst is shown. Based on the finding of thermodynamic stable
      nanophase of ZnS, we designed a strategy in which the deactivated ZnS nano
      photocatalyst could be recovered into its original state. This ZnS photocatalyst
      can be used repeatedly without being released into environment as nano-waste. The
      strategy uses material highly efficiently and is environmentally friendly.

PMID- 20689876
TI  - Interfacial entrapment of noble metal nanoparticles and nanorods capped with
      amphiphilic multiblock copolymer at a selective liquid-liquid interface.
AB  - An amphiphilic multiblock copolymer, [poly(4-vinylpyridine)-b-polystyrene-b
      poly(4-vinylpyridine)](n) (P4VP-PS-P4VP)(n) bearing trithiocarbonate moieties (-S
      CS-S-), was used as capping agent to fabricate the functional copolymer-capped Au
      nanoparticles. Due to the amphiphilic character of the multiblock copolymer, the
      (P4VP-PS-P4VP)(n)-capped Au nanoparticles were able to be entrapped and hence
      form a stable monolayer thin film at the (DMF-H(2)O)/diethyl ether interface.
      Note that DMF-H(2)O is a good mixed solvent for P4VP and a nonsolvent for PS,
      whereas diethyl ether is a good solvent for PS and a nonsolvent for P4VP. A
      similar procedure can be applied to prepare monolayer thin film of the (P4VP-PS
      P4VP)(n)-capped Ag nanoparticles at the (DMF-H(2)O)/diethyl ether interface,
      which exhibits enhanced surface Raman signal. We further demonstrate that the
      stable monolayer of (P4VP-PS-P4VP)(n)-capped Au nanorods can also be fabricated
      by using the ligand-exchange method.

PMID- 20689877
TI  - Photochemistry of HgBr(2) in methanol investigated using time-resolved X-ray
      liquidography.
AB  - We investigate the photoinduced dissociation of HgBr(2) in methanol and the
      ensuring structural dynamics of the photo-products over a time span from 100 ps
      to 1 MUs after photolysis at 267 nm by using time-resolved X-ray liquidography
      (TRXL). By making use of the atomic-level structural sensitivity of X-ray
      scattering and the superb 100 ps time resolution of X-ray pulses from a 3rd
      generation synchrotron, the structural dynamics of a chemical reaction in
      solution can be directly monitored. The measured time-dependent X-ray solution
      scattering signals, analyzed using global-fitting based on DFT calculations and
      MD simulations, show that photoexcited HgBr(2) dissociates via both two-body
      (HgBr + Br) and three-body (Hg + Br + Br) dissociation pathways with a ~2 : 1
      branching ratio. Following dissociation, the photoproducts recombine via three
      reactions involving Br species: (1) Hg + Br, (2) HgBr + Br, and (3) Br + Br. The
      associated rate constants and branching ratios are determined from the global
      fitting analysis. Also, we examine the energy dissipation from reacting solute
      molecules and relaxation of excited molecules to solvent bath accompanying the
      temperature rise of 0.54 K. Compared to a previous TRXL study of the
      photodissociation of HgI(2), the results of this work suggest that the
      photodissociation pathway of HgBr(2) is different from that of HgI(2), which
      dissociates predominantly via two-body dissociation, at least to within the
      currently available time resolution of ~100 ps. In addition, the error analysis
      of the fit parameters used in the global-fitting are discussed in detail with a
      comparison of various error estimation algorithms.

PMID- 20689878
TI  - Near-infrared luminescent copolymerized hybrid materials built from tin
      nanoclusters and PMMA.
AB  - Novel near-infrared (NIR) luminescent copolymerized hybrid materials were
      prepared by covalently grafting and physically doping Ln complexes (Ln = Er, Sm,
      Yb, and Nd) into a copolymer matrix built from nanobuilding blocks. The
      structures of the obtained hybrid materials were investigated by Fourier
      transform infrared (FTIR) spectra, nuclear magnetic resonance (NMR), gel
      permeation chromatography (GPC), and thermogravimetric analysis (TGA). In the
      photoluminescence studies, the hybrid materials showed characteristic NIR
      luminescence of corresponding Ln(3+) ions through intramolecular energy transfer
      from ligands to Ln(3+) ions. Transparent films of these materials can be easily
      prepared through spin-coating on indium tin oxide (ITO) glasses taking advantage
      of the matrix nature.

PMID- 20689879
TI  - Controlled fabrication of SnO(2) arrays of well-aligned nanotubes and nanowires.
AB  - Highly oriented SnO(2) nanotubes and nanowires arrays have been selectively
      fabricated via a convenient one-step wet-chemical approach using anodic aluminium
      oxide (AAO) as a hard template. Wall thickness of the SnO(2) nanotubes was
      tunable. The as-prepared nanostructures were composed of fine particles with
      sizes as small as 5 nm. Formation mechanism of SnO(2) nanostructure arrays with
      different shape is also discussed based on the experimental results. The
      structure, morphology, composition properties of the as-prepared samples were
      characterized using X-ray powder diffraction, transmission electron microscopy,
      energy dispersive X-ray spectrometry, scanning electron microscopy and Raman
      spectrum.

PMID- 20689880
TI  - P6Mo18O73 heteropolyanion and its four-copper complex: theoretical and
      experimental investigation.
AB  - The non-classical KP(6)Mo(18)O(73) heteropolyanion has been studied by the
      density functional theory (DFT) method, and the calculated geometry compares well
      with the experimental one. In fully oxidized [KP(6)Mo(18)O(73)](7-) state, the
      d(xy)-orbitals centered at eight "belt" Mo sites in the lower part of the
      "basket" are the major contributors to the LUMO and LUMO+1, while the LUMO+2
      orbital is mostly focused on the two polar parts. In contrast, the HOMOs
      indicates that the coordination of the KP(6)Mo(18) heteropolyanion to metal ions
      favorably occurs at the oxygen atoms from four external phosphates and two
      molybdates of the handle of the "basket". Compared with Wells-Dawson
      [P(2)Mo(18)O(62)](6-), the HOMO-LUMO gap in fully oxidized [KP(6)Mo(18)O(73)](7-)
      is much smaller, indicating much easier reduction that is consistent with the
      cyclic voltammogram. Both frontier orbitals and Mulliken analysis indicate that
      two of three blue electrons in [KP(6)Mo(18)O(73)](10-) (KP(6)Mo(18)-3e) have spin
      alpha while third blue electron has spin beta, in agreement with magnetic data.
      The four-copper complex of the non-classical KP(6)Mo(18)-3e heteropolyanion has
      been synthesized and structurally characterized; its structure supports the
      theoretical results such as reactivity and basicity of external oxygen sites.

PMID- 20689881
TI  - Density-functional based determination of intermolecular charge transfer
      properties for large-scale morphologies.
AB  - Theoretical studies of charge transport in organic conducting systems pose a
      unique challenge since they must describe both extremely short-ranged and fast
      processes (charge tunneling) and extremely long-ranged and slow ones (molecular
      ordering). The description of the mobility of electrons and holes in the hopping
      regime relies on the determination of intermolecular hopping rates in large-scale
      morphologies. Using Marcus theory these rates can be calculated from
      intermolecular transfer integrals and on-site energies. Here we present a
      detailed computational study on the accuracy and efficiency of density-functional
      theory based approaches to the determination of intermolecular transfer
      integrals. First, it is demonstrated how these can be obtained from quantum
      chemistry calculations by forming the expectation value of a dimer Fock operator
      with frontier orbitals of two neighboring monomers based on a projective
      approach. We then consider the prototypical example of one pair out of a larger
      morphology of tris(8-hydroxyquinolinato)aluminium (Alq(3)) and study the
      influence of computational parameters, e.g. the choice of basis sets, exchange
      correlation functional, and convergence criteria, on the calculated transfer
      integrals. The respective results are compared in order to derive an optimal
      strategy for future simulations based on the full morphology.

PMID- 20689882
TI  - Dynamic formation of self-organized corner-connected square metallocycles by
      stoichiometric control.
AB  - Corner-connected molecular squares were self-assembled from a three-component
      system formed by a bidentate ligand and two palladium or platinum complexes. The
      system is dynamic and the constitution of the species in solution can be
      modulated under stoichiometric control.

PMID- 20689883
TI  - Stabilization of zwitterionic aryltrifluoroborates against hydrolysis.
AB  - The presence of a proximal cationic group in zwitterionic aryltrifluoroborates
      such as o-(Ph(2)MeP)C(6)H(4)(BF(3)) stabilizes these compounds against
      hydrolysis.

PMID- 20689884
TI  - [18]Crown-6 rotator in spin-ladder compound of m-aminoanilinium([18]crown
      6)[Ni(dmit)2]-.
AB  - Supramolecular cations of HOPD+([18]crown-6) and HMPD+([18]crown-6) were
      introduced into [Ni(dmit)2]- salts (HOPD+: o-aminoanilinium, HMPD+: m
      aminoanilinium, and dmit2-: 2-thioxo-1,3-dithiole-4,5-dithiolate). Alternate
      layers of cations and anions were observed in the two new salts of
      (HOPD+)([18]crown-6)[Ni(dmit)2]- (1) and (HMPD+)([18]crown-6)[Ni(dmit)2]- (2).
      From X-ray crystal structural analyses, solid state 1H nuclear magnetic resonance
      (NMR) spectra, and dielectric constants, the thermal rotations of [18]crown-6 in
      both of the (HOPD+)([18]crown-6) and (HMPD+)([18]crown-6) supramolecules occurred
      at temperatures above approximately 200 K based on the orientational disorder in
      the crystal structures. The two-fold flip-flop motions of HOPD+ and HMPD+ cations
      in salts 1 and 2 were suppressed, due to the relatively large potential energy
      barriers. The [Ni(dmit)2]- anion formed pi-dimer arrangements in both salts, with
      a layer structure by lateral sulfur-sulfur interatomic contacts. Although the
      simple dimer model reproduced the magnetic properties of salt 1, the ladder
      arrangement of the pi-dimer in salt 2 yielded the magnetic behavior of a spin
      ladder with a spin-gap of 92.5 K. The temperature dependent magnetic
      susceptibility of salt 2 was well reproduced by the magnetic anisotropy of J1/J2
      approximately = 8 between the ladder-leg (J1: intra-dimer interaction) and ladder
      rung (J2: inter-dimer interaction). The [18]crown-6 supramolecular rotator of
      (HMPD+)([18]crown-6) was coexistent with the spin-ladder chain of [Ni(dmit)2]-
      anions in salt 2.

PMID- 20689885
TI  - Drug delivery of lipophilic pyrenyl derivatives by encapsulation in a water
      soluble metalla-cage.
AB  - The self-assembly of 2,4,6-tris(pyridin-4-yl)-1,3,5-triazine (tpt) triangular
      panels with p-cymene (p-Pr(i)C(6)H(4)Me) ruthenium building blocks and 2,5
      dioxydo-1,4-benzoquinonato (dobq) bridges, in the presence of a functionalised
      pyrenyl derivative (pyrene-R), affords the triangular prismatic host-guest
      compounds [(pyrene-R) [symbol: see text] Ru(6)(p
      Pr(i)C(6)H(4)Me)(6)(tpt)(2)(dobq)(3)](6+) ([(pyrene-R) [symbol: see text]
      1](6+)). The inclusion of eight mono-substituted pyrenyl derivatives including
      biologically relevant structures (a = 1-pyrenebutyric acid, b = 1-pyrenebutanol,
      c = 1-pyrenemethylamine, d = 1-pyrenemethylbutanoate, e = 1-(4,6-dichloro-1,3,5
      triazin-2-yl)pyrene, f = N-hexadecylpyrene-1-sulfonamide, g = pyrenyl ethacrynic
      amide and h = 2-(pyren-1-ylmethylcarbamoyl) phenyl acetate), and a di-substituted
      pyrenyl derivative (i = 1,8-bis(3-methyl-butyn-1-yl-3-ol)pyrene), has been
      accomplished. The carceplex nature of these systems with the pyrenyl moiety being
      firmly encapsulated in the hydrophobic cavity of the cage with the functional
      groups pointing outwards was confirmed by NMR ((1)H, 2D, DOSY) spectroscopy and
      electrospray ionization mass spectrometry (ESI-MS). The cytotoxicities of these
      water-soluble compounds have been established using human ovarian A2780 cancer
      cells. All the host-guest systems are more cytotoxic than the empty cage itself
      [1][CF(3)SO(3)](6) (IC(50) = 23 microM), the most active carceplex [f [symbol:
      see text] 1][CF(3)SO(3)](6) is an order of magnitude more cytotoxic.

PMID- 20689886
TI  - Copper(I) complexes with N-(diisopropoxythiophosphoryl)thiobenzamide
      PhC(S)NHP(S)(OiPr)2.
AB  - Reaction of the potassium salt of N-thiophosphorylthiobenzamide
      PhC(S)NHP(S)(OiPr)(2) (HL) with CuI in aqueous EtOH leads to the tetranuclear
      [Cu(4)L(4)] and the polynuclear [KCuL(2)](n) complexes, while the same reactions
      using the lithium or sodium salts of HL exclusively lead to the tetramer
      [Cu(4)L(4)]. Reaction of KL with the mixture of CuI and 2,2'-bipyridine (bpy) or
      1,10-phenanthroline (phen) leads to the mononuclear complexes [Cu(bpy)L] and
      [Cu(phen)L]. The same complexes were obtained by the reaction of [Cu(4)L(4)] with
      bpy or phen.

PMID- 20689887
TI  - Discovery of a strongly apoptotic ruthenium complex through combinatorial
      coordination chemistry.
AB  - A strategy for combinatorial parallel coordination chemistry is introduced that
      provides access to libraries of tris-heteroleptic ruthenium complexes in an
      economical fashion. Using this method, a library of 560 constitutionally unique,
      monocationic ruthenium complexes was synthesized, followed by a screening for
      anticancer activity and resulting in the identification of three hits with
      promising cytotoxic properties in HeLa cancer cells. A subsequent structure
      activity relationship led to the discovery of the surprisingly simple anticancer
      complex [Ru(tBu(2)bpy)(2)(phox)]PF(6) (complex 1), with tBu(2)bpy = 4,4'-di-tert
      buty-2,2'-bipyridine and Hphox = 2-(2'-hydroxyphenyl)oxazoline, displaying an
      LC(50) value in HeLa cells of 1.3 microM and 0.3 microM after incubation for 24
      and 72 h, respectively. Complex 1 also shows remarkable antiproliferative and
      apoptotic properties at submicromolar concentrations in more clinically relevant
      Burkitt-like lymphoma cells. A reduction of the mitochondrial membrane potential
      by 1 indicates the involvement of the intrinsic pathway of programmed cell death.
      Further investigations reveal that 1 requires caspase-3 for the induction of
      apoptosis but is insensitive to the proapoptotic and antiapoptotic proteins Smac
      and Bcl-2, respectively.

PMID- 20689888
TI  - Effects of water on the structure and low/high temperature stability of confined
      proteins.
AB  - In this study well-characterized model proteins were confined in silica
      nanoporous matrices. Confinement of the proteins in silica matrices allowed us to
      explore the role of water hydrogen bonding on the structures of the proteins in a
      broad range of temperatures (-120 degrees C to 95 degrees C). At low temperatures
      confinement suppressed freezing of water, which remained in the liquid state. We
      obtained direct evidence that the changes in the hydrogen bonding of water
      induced changes in the structure of confined proteins. At high temperatures, a
      reduction of hydrogen bonding of water facilitated protein-silica interactions
      and the confined proteins underwent denaturation. However, the incorporation of
      the osmolyte, trehalose, reduced protein-silica interactions, and altered the
      hydrogen bonding of water. As a result, the high temperature thermal stability of
      the confined proteins was greatly improved.

PMID- 20689889
TI  - Structural and theoretical insights into the perturbation of uranium-rhenium
      bonds by dative Lewis base ancillary ligands.
AB  - Amine-elimination gave the two uranium-rhenium complexes
      [(Ts(Xy))(THF)(n)URe(eta(5)-C(5)H(5))(2)] [Ts(Xy) = HC(SiMe(2)N-3,5
      Me(2)C(6)H(3))(3); n = 0 or 1]; structural and theoretical analyses, and
      comparison to [(Tren(TMS))URe(eta(5)-C(5)H(5))(2)] [Tren(TMS) =
      N(CH(2)CH(2)NSiMe(3))(3)], reveal an increasing sigma-component to the U-Re bond
      upon removal of dative ancillary ligands from uranium with the pi-component
      remaining essentially invariant.

PMID- 20689890
TI  - Probing for non-statistical effects in dissociation of the 1-methylallyl radical.
AB  - The 1-methylallyl radical loses a hydrogen atom following photoexcitation to its
      lowest valence electronically excited state and displays statistical behavior in
      decomposition, implying that the presence of methyl rotors cannot be depended
      upon as an indicator for non-statistical dissociation dynamics in hydrocarbon
      radicals.

PMID- 20689891
TI  - Novel homo- and heterobinuclear ball-type phthalocyanines: synthesis and
      electrochemical, electrical, EPR and MCD spectral properties.
AB  - The mononuclear Fe(II) phthalocyanine 2 and ball-type homobinuclear Fe(II)-Fe(II)
      and Cu(II)-Cu(II) phthalocyanines, 3 and 4 respectively, were synthesized from
      the corresponding 4,4'-[1,1'-methylenebis-(naphthalene-2,1
      diyl)]bis(oxy)diphthalonitrile 1, and then ball-type heterobinuclear Fe(II)
      Cu(II) phthalocyanine 5 was synthesized from 2. The novel compounds 4 and 5 have
      been characterized by elemental analysis, UV/vis, IR and MALDI-TOF mass
      spectroscopies. Electron paramagnetic resonance and magnetic circular dichroism
      measurements of 3, 4 and 5 were also examined. The voltammetric measurements of
      the complexes showed the formation of various electrochemically stable ligand-
      and metal-based mixed-valence species, due to the intramolecular interactions
      between the two MPc units, especially in ball-type binuclear iron(II)
      phthalocyanine. Impedance spectroscopy and d.c. conductivity measurements of 4
      and 5 were performed as a function of temperature (295-523 K) and frequency (40
      10(5) Hz). While room temperature impedance spectra consist of a curved line, a
      transformation into a full semicircle with increasing temperature was observed
      for both compounds.

PMID- 20689892
TI  - Structural diversity in polyamine Lewis base stabilised lithium aryloxides.
AB  - Five new lithium aryloxide complexes stabilised by polyamine ligands have been
      synthesised by simple deprotonation reactions of the parent aryl alcohols H-OAr
      [OAr = OC(6)H(5), OC(6)H(2)-2,4,6-(Me)(3) and OC(6)H(2)-2,6-((t)Bu)(2)-4-(Me)]
      with LiN(SiMe(3))(2) in the presence of the Lewis bases N,N,N',N'
      tetramethylethylenediamine (TMEDA) and N,N,N',N'',N''
      pentamethyldiethylenetriamine (PMDETA). All the compounds have been characterised
      by multinuclear NMR and X-ray crystallographic studies. The PMDETA derivative of
      the phenol adopts a tetrameric ladder-like structural motif in the solid state,
      exhibiting an unusual bridging coordination mode of the N-donor ligand. The 2,4,6
      trimethylphenol derivatives exhibit dimeric (TMEDA), and tetrameric (PMDETA)
      structural motifs in the solid state. Meanwhile, the TMEDA and PMDETA derivatives
      of the sterically hindered 2,6-di-tert-butyl-4-methylphenol exhibit a rare
      monomeric structural motifs, which appears to remain unaltered in C(6)D(6)
      solution.

PMID- 20689893
TI  - Zn(3)(4-OOCC(6)H(4)PO(3))(2): A polar metal phosphonate with pillared layered
      structure showing SHG-activity and large dielectric anisotropy.
AB  - A new metal phosphonate Zn(3)(4-OOCC(6)H(4)PO(3))(2) (1) is reported which
      crystallizes in orthorhombic space group Pca2(1). It shows a pillared layered
      structure in which the {ZnO(4)}, {ZnO(5)} and {PO(3)C} polyhedra are connected
      through corner- or edge-sharing to form an inorganic layer in the ab plane which
      contains 4- and 5-member rings. These layers are pillared by the uni-oriented 4
      carboxylatephenylphosphonate ligands, thus leading to a polar 3D architecture.
      The dielectric anisotropy measurements of a single crystal of 1 reveal that
      dielectric constant along the inter-layer is larger than that along the intra
      layer with a ratio of about 2.3. Second harmonic generation (SHG) activity is
      observed.

PMID- 20689894
TI  - A nanostructured graphene/polyaniline hybrid material for supercapacitors.
AB  - A flexible graphene/polyaniline hybrid material as a supercapacitor electrode was
      synthesized by an in situ polymerization-reduction/dedoping-redoping process.
      This product was first prepared in an ethylene glycol medium, then treated with
      hot sodium hydroxide solution to obtain the reduced graphene oxide/polyaniline
      hybrid material. Sodium hydroxide also acted as a dedoping reagent for
      polyaniline in the composite. After redoping in an acidic solution, the thin,
      uniform and flexible conducting graphene/polyaniline product was obtained with
      unchanged morphology. The chemical structure of the materials was characterized
      by X-ray photoelectron spectroscopy and Raman spectroscopy. The composite
      material showed better electrochemical performances than the pure individual
      components. A high specific capacitance of 1126 F g(-1) was obtained with a
      retention life of 84% after 1000 cycles for supercapacitors. The energy density
      and power density were also better than those of pure component materials.

PMID- 20689895
TI  - First synthetic entry to the trimer stage of 5,6-dihydroxyindole polymerization:
      ortho-alkynylaniline-based access to the missing 2,7':2',7''-triindole.
AB  - 5,6-Dihydroxyindole oligomers are valuable synthetic targets for the structural
      characterization of eumelanin biopolymers as well as for the realization of
      bioinspired functional materials. An ortho-alkynylaniline-based strategy allowed
      the first access to a trimer, the missing 5,5',5'',6,6',6''-hexaacetoxy
      2,7':2',7''-triindole, and its detection as a minor intermediate en route from
      5,6-dihydroxyindole to eumelanin-like polymers.

PMID- 20689896
TI  - Glucose response of dissolved-core alginate microspheres: towards a continuous
      glucose biosensor.
AB  - Microparticle optical sensors hold potential as implantable smart materials for
      in vivo analysis. In this work, the reversible response of dissolved-core
      alginate microspheres containing a homogeneous fluorescence resonance energy
      transfer (FRET)-based competitive binding assay for glucose was evaluated. The
      layer-by-layer self assembly technique was used to deposit multilayered nanofilm
      coatings on the alginate microspheres containing the assay, thereby stabilizing
      the sensor system when the alginate was de-crosslinked. The response to glucose
      was then determined in DI water and simulated interstitial fluid (SIF) using a
      flow cell to establish controlled, dynamic flow conditions for demonstrating
      reversibility. The glucose sensitivity under dynamic conditions was estimated to
      be 0.52%/mM glucose in DI water and 0.6%/mM glucose in simulated interstitial
      fluid; in both cases, the analytical response range was 0-30 mM glucose, covering
      both physiological (normoglycemia) and pathophysiological range (hyperglycemia
      and hypoglycemia). The sensor demonstrated a repeatable and reproducible response
      when tested over a period of one month, under dynamic flow conditions. Finally,
      in vitro cytotoxicity assays performed with L929 mouse fibroblast cell lines
      suggested that the dissolved-core alginate microsphere sensor system with
      nanofilm coating has sufficient biocompatibility for use as implantable glucose
      biosensors.

PMID- 20689897
TI  - New sulfur-oxygen mixed-donor ligand N,N'-dimethyl-piperazine-3-oxo-2-thione
      (Me2pipto) and its Ni(II) and Fe(II) complexes.
AB  - Structural and electronic features of the novel title sulfur-oxygen donor ligand
      Me(2)pipto (1), are discussed in comparison with those of the corresponding
      dithione ligand Me(2)pipdt. A tuning of the electronic and coordination
      properties of the ligand, relatable to the soft/hard power of the donor atoms, is
      achieved. Coordination properties have been checked towards Ni(II) and Fe(III)
      cations obtaining [Ni(Me(2)pipto)(3)](BF(4))(2) (2) and
      [Fe(Me(2)pipto)(3)](BF(4))(2) (4) complexes, which show significant differences
      when compared with the corresponding reaction products when using Me(2)pipdt.

PMID- 20689898
TI  - Polypeptide-guided assembly of conducting polymer nanocomposites.
AB  - A strategy for fabrication of electroactive nanocomposites with nanoscale
      organization, based on self-assembly, is reported. Gold nanoparticles are
      assembled by a polypeptide folding-dependent bridging. The polypeptides are
      further utilized to recruit and associate with a water soluble conducting
      polymer. The polymer is homogenously incorporated into the nanocomposite, forming
      conducting pathways which make the composite material highly conducting.

PMID- 20689899
TI  - Comments on "A new look at low-energy nuclear reaction research".
AB  - Cold fusion researchers have accumulated a large body of anomalous results over
      the last 20 years that they claim proves a new, mysterious nuclear reaction is
      active in systems they study. Krivit and Marwan (J. Environ. Monit., 2009, 11,
      1731) give a brief and wholly positive view of this body of research.
      Unfortunately, cold fusion researchers routinely ignore conventional explanations
      of their observations, and claim much greater than the real accuracy and
      precision for their techniques. This paper attempts to equally briefly address
      those aspects of the field with the intent of providing a balanced view of the
      field, and to establish some criteria for subsequent publications in this arena.

PMID- 20689900
TI  - Trace voltammetric detection of serotonin at carbon electrodes: comparison of
      glassy carbon, boron doped diamond and carbon nanotube network electrodes.
AB  - The characteristics of three different carbon electrodes, glassy carbon (GC),
      oxygen-terminated polycrystalline boron-doped diamond (pBDD) and "pristine"
      carbon nanotube networks (CNTN) as voltammetric sensors for detection of the
      neurotransmitter serotonin have been investigated. For each electrode, detection
      sensitivity was determined using cyclic voltammetry (CV), a technique often used
      to provide information on chemical identity in electrochemical assays. The CNTN
      electrodes were found to exhibit background current densities ca. two orders of
      magnitude smaller than the GC electrode and ca. twenty times smaller than pBDD,
      as a consequence of their "pristine" low capacitance and low surface coverage.
      This was a major factor in determining serotonin detection limits from CV, of 10
      nM for the CNTN electrode, 500 nM for pBDD and 2 microM for GC. The two most
      sensitive electrodes (CNTN and pBDD) were further investigated in terms of
      resistance to electrode fouling. CV analysis showed that fouling was less on the
      pBDD electrode compared to the CNTN and, furthermore, for the case of pBDD could
      be significantly minimised by careful selection of the CV potential limits, in
      particular by scanning the electrode potential to suitably cathodic values after
      oxidation of the serotonin.

PMID- 20689902
TI  - Analytical connotations of point-of-care testing.
AB  - The main objective of this Tutorial Review is to approach the modern principles
      and practices of Analytical Chemistry to Point-of-Care Testing (POCT) systems in
      order to contribute to improve both the development of new devices and the
      reliable application of the existing ones. In this article, after
      contextualization of the topic, POCT systems (POCTs) are fully defined using
      several approaches. The requirements of a POCT system to be a robust and reliable
      tool available to patients and medical workers are described as well as their
      desirable complementary characteristics. In addition, the technical components of
      POCTs materialized in the implementation of the steps of the analytical processes
      (sample introduction, sample processing, visual or instrumental detection, and
      data processing) are outlined. Besides, analytical properties assigned to POCTs
      and to their quantitative and qualitative results are highlighted. Special
      emphasis is given to Quality Assurance and Quality Control procedures, which are
      essential aspects to achieving reliable results. Finally, decision making based
      on the results obtained with POCTs is discussed as are their benefits and
      drawbacks.

PMID- 20689903
TI  - [Thrombotic-thrombocytopenic purpura].
AB  - Thrombotic-thrombocytopenic purpura (TTP) is a microangiopathic disorder
      characterized by multiple von Willebrand-Factor (vWF) rich microthrombi affecting
      the arterioles and capillary vessels of several organs. Ultra large von
      Willebrand multimers cause the blood clotting process by linking to platelets due
      to a lack of a plasma metalloprotease named ADAMTS13. Deficiency of this vWF
      cleaving enzyme is caused by an inborn mutation in the gene coding or, more
      often, by acquired autoantibodies that inhibit ADAMTS13. TTP is a life
      threatening disease which requires urgent admission to a hematological centre.
      Plasmapheresis therapy should be started immediately when diagnosis of primary
      TTP is likely. Patients typically present with schistozytes, hemolysis,
      thrombocytopenia and neurological abnormalities such as headache, focal deficits
      or coma. The monoclonal CD20 antibody rituximab targets ADAMTS13 antibody
      production and has the potential to be an effective therapy for relapsed TTP or
      initial treatment to shorten duration of plasma exchange.

PMID- 20689904
TI  - Nutrient compensatory foraging in a free-living social insect.
AB  - The geometric framework model predicts that animal foraging decisions are
      influenced by their dietary history, with animals targeting a combination of
      essential nutrients through compensatory foraging. We provide experimental
      confirmation of nutrient-specific compensatory foraging in a natural, free-living
      population of social insects by supplementing their diet with sources of protein-
      or carbohydrate-rich food. Colonies of the ant Iridomyrmex suchieri were provided
      with feeders containing food rich in either carbohydrate or protein for 6 days,
      and were then provided with a feeder containing the same or different diet. The
      patterns of recruitment were consistent with the geometric framework: while
      feeders with a carbohydrate diet typically attracted more workers than did
      feeders with protein diet, the difference in recruitment between the two
      nutrients was smaller if the colonies had had prior access to carbohydrate than
      protein. Further, fewer ants visited feeders if the colony had had prior access
      to protein than to carbohydrates, suggesting that the larvae play a role in
      worker foraging behaviour.

PMID- 20689905
TI  - The SSR-based molecular profile of 1005 grapevine (Vitis vinifera L.) accessions
      uncovers new synonymy and parentages, and reveals a large admixture amongst
      varieties of different geographic origin.
AB  - A collection of 1005 grapevine accessions was genotyped at 34 microsatellite loci
      (SSR) with the aim of analysing genetic diversity and exploring parentages. The
      comparison of molecular profiles revealed 200 groups of synonymy. The removal of
      perfect synonyms reduced the database to 745 unique genotypes, on which
      population genetic parameters were calculated. The analysis of kinship uncovered
      74 complete pedigrees, with both parents identified. Many of these parentages
      were not previously known and are of considerable historical interest, e.g.
      Chenin blanc (Sauvignon * Traminer rot), Cove (Harslevelu selfed), Incrocio
      Manzoni 2-14 and 2-15 (Cabernet franc * Prosecco), Lagrein (Schiava gentile *
      Teroldego), Malvasia nera of Bolzano (Perera * Schiava gentile), Manzoni moscato
      (Raboso veronese * Moscato d'Amburgo), Moscato violetto (Moscato bianco *
      Duraguzza), Muscat of Alexandria (Muscat blanc a petit grain * Axina de tres
      bias) and others. Statistical robustness of unexpected pedigrees was reinforced
      with the analysis of an additional 7-30 SSRs. Grouping the accessions by profile
      resulted in a weak correlation with their geographical origin and/or current area
      of cultivation, revealing a large admixture of local varieties with those most
      widely cultivated, as a result of ancient commerce and population flow. The SSRs
      with tri- to penta-nucleotide repeats adopted for the present study showed a
      great capacity for discriminating amongst accessions, with probabilities of
      identity by chance as low as 1.45 * 10(-27) and 9.35 * 10(-12) for unrelated and
      full sib individuals, respectively. A database of allele frequencies and SSR
      profiles of 32 reference cultivars are provided.

PMID- 20689906
TI  - Quantitative resistance to late blight from Solanum berthaultii cosegregates with
      R(Pi-ber): insights in stability through isolates and environment.
AB  - Genetic resistance is a valuable tool in the fight against late blight of
      potatoes but little is known about the stability and specificity of quantitative
      resistance including the effect of defeated major resistance genes. In the
      present study we investigated the effect of different isolates of Phytophthora
      infestans on the mode of action of R(Pi-ber), an R-gene originating from Solanum
      berthaultii. The experiments were conducted on progenies derived from two
      reciprocal inter-specific backcrosses of Solanum tuberosum and S. berthaultii.
      The plant-pathogen interaction was tested in diverse environments including
      field, greenhouse and growth chamber conditions. The R(Pi-ber) gene provided
      complete resistance against a US8 isolate of P. infestans in all trials. When
      isolates compatible with R(Pi-ber) were used for inoculation, a smaller, but
      significant resistance effect was consistently detected in the same map position
      as the R-gene. This indicates that this R-gene provides a residual resistance
      effect, and/or that additional resistance loci are located in this genomic region
      of chromosome X. Additional quantitative resistance loci (QRL) were identified in
      the analyzed progenies. While some of the QRL (such as those near TG130 on
      chromosome III) were effective against several isolates of the pathogen, others
      were isolate specific. With a single exception, the S. berthaultii alleles were
      associated with a decrease in disease severity. Resistance loci reported in the
      present study co-locate with previously reported R-genes and QRL to P. infestans
      and other pathogens.

PMID- 20689907
TI  - The role of general quality improvement measures in decreasing the burden of
      endemic MRSA in a medical-surgical intensive care unit.
AB  - PURPOSE: To determine whether any of several quality improvement interventions
      with none specifically targeting methicillin-resistant Staphylococcus aureus
      (MRSA) were associated with a decline in endemic MRSA prevalence in an intensive
      care unit (ICU) where active screening and contact isolation precautions for
      known MRSA colonised patients are not practised. SETTING: Medical-surgical ICU
      with 2,000 admissions/year. DESIGN: 8.5-year retrospective time-series analysis.
      INTERVENTIONS: ICU re-location, antibiotic stewardship utilising computerised
      decision-support and infectious-diseases physician rounds, dedicated ICU
      infection control practitioners, alcohol-based hand rub solution (ABHRS). METHOD:
      Regression modelling was used to evaluate trends in S. aureus prevalence density
      (monthly clinical isolates per 1,000 patient-days), antibiotic consumption,
      infection control consumables, ABHRS and their temporal relationship with MRSA
      prevalence. RESULTS: Methicillin-resistant S. aureus prevalence density decreased
      by 83% [95% confidence interval (CI) -68% to -91%, p < 0.001]. Rates of MRSA
      bacteraemia decreased 89% (95% CI -79% to -94%, p = 0.001) with no statistically
      significant change in methicillin-sensitive S. aureus bacteraemia. Hospital MRSA
      prevalence density decreased 17% (95% CI -5% to -27%, p = 0.005), suggesting that
      ICU was not shifting MRSA elsewhere. In ICU, broad-spectrum antibiotic use
      decreased by 26% (95% CI -12% to -38%, p = 0.008), coinciding with a decrease in
      MRSA, but time-series analysis did not show a significant association. On
      multivariate analysis, only ABHRS was significantly associated with a decrease in
      MRSA, but it was formally introduced late in the study period when MRSA was
      already in decline. CONCLUSION: General quality improvement measures were
      associated with a decrease in endemic MRSA in a high-risk setting without use of
      resource-intensive active surveillance and isolation practices.

PMID- 20689908
TI  - Quantitative CT in ARDS: towards a clinical tool?

PMID- 20689909
TI  - Extrapolation from ten sections can make CT-based quantification of lung aeration
      more practicable.
AB  - PURPOSE: Clinical applications of quantitative computed tomography (qCT) in
      patients with pulmonary opacifications are hindered by the radiation exposure and
      by the arduous manual image processing. We hypothesized that extrapolation from
      only ten thoracic CT sections will provide reliable information on the aeration
      of the entire lung. METHODS: CTs of 72 patients with normal and 85 patients with
      opacified lungs were studied retrospectively. Volumes and masses of the lung and
      its differently aerated compartments were obtained from all CT sections. Then
      only the most cranial and caudal sections and a further eight evenly spaced
      sections between them were selected. The results from these ten sections were
      extrapolated to the entire lung. The agreement between both methods was assessed
      with Bland-Altman plots. RESULTS: Median (range) total lung volume and mass were
      3,738 (1,311-6,768) ml and 957 (545-3,019) g, the corresponding bias (limits of
      agreement) were 26 (-42 to 95) ml and 8 (-21 to 38) g, respectively. The median
      volumes (range) of differently aerated compartments (percentage of total lung
      volume) were 1 (0-54)% for the nonaerated, 5 (1-44)% for the poorly aerated, 85
      (28-98)% for the normally aerated, and 4 (0-48)% for the hyperaerated subvolume.
      The agreement between the extrapolated results and those from all CT sections was
      excellent. All bias values were below 1% of the total lung volume or mass, the
      limits of agreement never exceeded +/- 2%. CONCLUSION: The extrapolation method
      can reduce radiation exposure and shorten the time required for qCT analysis of
      lung aeration.

PMID- 20689910
TI  - Restoring arterial pressure with norepinephrine improves muscle tissue
      oxygenation assessed by near-infrared spectroscopy in severely hypotensive septic
      patients.
AB  - PURPOSE: To examine the consequences of administration of norepinephrine on
      muscle tissue oxygenation in severely hypotensive septic shock patients. METHODS:
      This was a prospective observational study conducted in a medical intensive care
      unit of a university hospital. We included 28 septic shock patients that received
      early volume resuscitation. All were eligible for receiving norepinephrine
      because of life-threatening hypotension and low diastolic arterial pressure.
      Muscle tissue oxygen saturation (StO2) and its changes during a vascular
      occlusion test were measured at the level of the thenar eminence using a near
      infrared spectroscopy (NIRS) device. Transpulmonary thermodilution cardiac index
      (CI) and NIRS-derived variables were obtained before and after the mean arterial
      pressure (MAP) was increased by norepinephrine. The baseline StO2 and the
      vascular occlusion test-derived variables of 17 healthy volunteers were measured
      and served as controls. RESULTS: In healthy volunteers, StO2 ranged between 75
      and 90% and StO2 recovery slopes ranged between 1.5 and 3.4%/s. Administration of
      norepinephrine, which was associated with an increase in MAP from 54 +/- 8 to 77
      +/- 9 mmHg (p < 0.05), also induced increases in CI from 3.14 +/- 1.03 to 3.61 +/
      1.28 L/min/m2 (p < 0.05), in StO2 from 75 +/- 9 to 78 +/- 9% (p < 0.05) and in
      StO2 recovery slope from 1.0 +/- 0.6 to 1.5 +/- 0.7%/s (p < 0.05). CONCLUSIONS:
      Norepinephrine administration aimed at achieving a MAP higher than 65 mmHg in
      septic shock patients with life-threatening hypotension resulted in improvement
      of NIRS variables measured at the level of the thenar eminence.

PMID- 20689913
TI  - Comment on dexmedetomidine systematic review and meta-analysis methodology.

PMID- 20689914
TI  - Bronchoalveolar lavage for pandemic influenza A (H1N1)v pneumonia in critically
      ill patients.

PMID- 20689911
TI  - Secondary adrenal insufficiency in the acute phase of pediatric traumatic brain
      injury.
AB  - PURPOSE: A high incidence of secondary adrenal insufficiency (AI) has been
      reported several months after a traumatic brain injury (TBI) in pediatric
      patients. Data from studies in adults suggest that AI may occur during the acute
      phase of TBI, with potential negative effects in the management of these
      vulnerable patients. The aim of this study was to describe the prevalence and the
      characteristics of AI in the acute phase of pediatric TBI. METHODS: Adrenal
      function was systematically evaluated in patients admitted to the pediatric
      intensive care unit following a TBI. Serial measurements of cortisol (9 samples)
      and adrenocorticotropic hormone (ACTH) were drawn from the second morning to the
      third morning post admission. Secondary AI was defined as all cortisols < 200
      nmol/l (6 MUg/dl) with ACTH < 12 pmol/l. RESULTS: Twenty-eight patients (2-15
      years old) were evaluated. Secondary AI occurred in ten (36%) patients. AI was
      more frequent in patients with intracranial hypertension (p < 0.05). Patients
      with AI required longer mechanical ventilation (p < 0.05), and a non-significant
      trend for a higher Pediatric Logistic Organ Dysfunction score (p = 0.09) and
      greater norepinephrine dose (p = 0.11) was observed. CONCLUSIONS: Secondary AI is
      frequent during the acute phase of pediatric TBI, particularly when intracranial
      hypertension is present. Systematic assessment of pituitary function after TBI
      appears to be essential. A randomized clinical trial is warranted to evaluate the
      benefits of hormonal replacement therapy in TBI patients with AI.

PMID- 20689915
TI  - Transcranial Doppler for brain death after decompressive craniectomy: persistence
      of cerebral blood flow with flat EEG.

PMID- 20689916
TI  - Monitoring the microcirculation in the critically ill patient: current methods
      and future approaches.
AB  - PURPOSE: To discuss the techniques currently available to evaluate the
      microcirculation in critically ill patients. In addition, the most clinically
      relevant microcirculatory alterations will be discussed. METHODS: Review of the
      literature on methods used to evaluate the microcirculation in humans and on
      microcirculatory alterations in critically ill patients. RESULTS: In experimental
      conditions, shock states have been shown to be associated with a decrease in
      perfused capillary density and an increase in the heterogeneity of
      microcirculatory perfusion, with non-perfused capillaries in close vicinity to
      perfused capillaries. Techniques used to evaluate the microcirculation in humans
      should take into account the heterogeneity of microvascular perfusion.
      Microvideoscopic techniques, such as orthogonal polarization spectral (OPS) and
      sidestream dark field (SDF) imaging, directly evaluate microvascular networks
      covered by a thin epithelium, such as the sublingual microcirculation. Laser
      Doppler and tissue O(2) measurements satisfactorily detect global decreases in
      tissue perfusion but not heterogeneity of microvascular perfusion. These
      techniques, and in particular laser Doppler and near-infrared spectroscopy, may
      help to evaluate the dynamic response of the microcirculation to a stress test.
      In patients with severe sepsis and septic shock, the microcirculation is
      characterized by a decrease in capillary density and in the proportion of
      perfused capillaries, together with a blunted response to a vascular occlusion
      test. CONCLUSIONS: The microcirculation in humans can be evaluated directly by
      videomicroscopy (OPS/SDF) or indirectly by vascular occlusion tests. Of note,
      direct videomicroscopic visualization evaluates the actual state of the
      microcirculation, whereas the vascular occlusion test evaluates microvascular
      reserve.

PMID- 20689917
TI  - Early postoperative delirium after open-heart cardiac surgery is associated with
      decreased bispectral EEG and increased cortisol and interleukin-6.
AB  - PURPOSE: It is difficult to substantiate the clinical diagnosis of postoperative
      delirium with objective parameters in intensive care units (ICU). The purpose of
      this study was to analyze (1) whether the bilateral bispectral (BIS) index, (2)
      cortisol as a stress marker, and (3) interleukin-6 as a marker of inflammation
      were different in delirious patients as compared to nondelirious ones after
      cardiac surgery. METHODS: On the first postoperative day, delirium was analyzed
      in 114 patients by using the confusion assessment method for ICU (CAM-ICU).
      Bilateral BIS data were determined; immediately thereafter plasma samples were
      drawn to analyze patients' blood characteristics. The current ICU medication,
      hemodynamic characteristics, SOFA and APACHE II scores, and artificial
      ventilation were noted. RESULTS: Delirium was detected at 19.1 +/- 4.8 h after
      the end of surgery in 32 of 114 patients (28%). Delirious patients were
      significantly older than nondelirious ones and were artificially ventilated 4.7
      fold more often during the testing. In delirious patients, plasma cortisol and
      interleukin-6 levels were higher (p = 0.01). The mean BIS index was significantly
      lower in delirious patients (72.6 (69.6-89.1); median [interquartile range (IQR),
      25th-75th percentiles] than in nondelirious patients, 84.8 (76.8-89.9). BIS EEG
      raw data analysis detected significant lower relative alpha and higher theta
      power. A significant correlation was found between plasma cortisol levels and BIS
      index. CONCLUSIONS: Early postoperative delirium after cardiac surgery was
      characterized by increased stress levels and inflammatory reaction. BIS index
      measurements showed lower cortical activity in delirious patients with a low
      sensitivity (27%) and high specificity (96%).

PMID- 20689918
TI  - Comparison of cardiac output and blood volumes in intrathoracic compartments
      measured by ultrasound dilution and transpulmonary thermodilution methods.
AB  - PURPOSE: To compare cardiac output (CO) and blood volumes measured by
      COstatus((r)) (Transonic Systems Inc., NY, USA) versus PiCCO (Philips IntelliVue
      MP40 with PiCCO-technology module M3012A#10, Netherlands) in adult ICU patients.
      METHODS: This was a prospective single-center study. Each of the 30 patients
      studied received a 5-Fr Pulsiocath femoral arterial and a standard central venous
      catheter. Twenty ml of iced 5% dextrose solution was injected for PiCCO
      measurements. For COstatus measurements, an extracorporeal arteriovenous loop,
      with two sensors placed on it, was connected between the Pulsiocath femoral
      arterial and central venous catheters. Blood was circulated through this loop at
      12 ml/min for 5-8 min using a pump. Twenty ml of warm saline was injected into
      the venous side for measurements. For each method, three injections were averaged
      for comparison. RESULTS: A good agreement for measured CO (range 3.65-16.3 l/min)
      with a percentage error of 20% was observed, with r = 0.95, bias = -0.037 l/min.
      PiCCO's global end-diastolic volume (GEDV) was 2.5 times larger than the
      analogous COstatus's total end-diastolic volume (TEDV) [TEDV = 0.28 * GEDV + 176
      ml]. PiCCO's intrathoracic blood volume (ITBV) was larger than the analogous
      COstatus's central blood volume (CBV) [CBV = 0.73 * (ITBV) +78 ml]. CONCLUSIONS:
      CO measured by COstatus was found to be equivalent and hence interchangeable with
      PiCCO in this study population. COstatus blood volumes were found to be within
      the expected physiological range whilst PiCCO blood volumes were significantly
      higher, which was also observed in other studies. Future studies using 3D
      echo/MRI are required to validate these blood volumes.

PMID- 20689919
TI  - Use of ultrasonography in hemicraniectomized patients: a report of two cases.

PMID- 20689920
TI  - Regional tidal ventilation and compliance during a stepwise vital capacity
      manoeuvre.
AB  - PURPOSE: To determine whether, during mechanical ventilation, an optimal positive
      end-expiratory pressure (PEEP) can be identified by measurement of regional tidal
      volume and compliance [V (T(reg)), C (RS(reg))]. METHODS: Sixteen anaesthetized
      intubated neonatal piglets underwent a stepwise vital capacity manoeuvre
      performed during pressure control ventilation, with 5 cmH2O PEEP increments to 25
      cmH2O, and decrements to 0 cmH2O. Peak inflating pressure was 10 cmH2O above PEEP
      throughout. The manoeuvre was performed in the normal lung, after repeated saline
      lavage and after surfactant therapy. Global V (T) and C (RS) were measured at the
      airway opening; V (T(reg)) and C (RS(reg)) were measured in the ventral, medial
      and dorsal lung using electrical impedance tomography (EIT). RESULTS: Most
      uniform distribution of regional tidal ventilation was noted during PEEP
      decrements after lung recruitment, at varying PEEP levels. In the lavaged and
      surfactant-treated lung the PEEP optimal for ventilation distribution was also
      associated with highest mean V (T(reg)) [lavaged: 95 +/- 9.3% of maximum, mean +/
      standard deviation (SD); surfactant-treated: 92 +/- 17%] and global V (T) (96 +/
      10%; 96 +/- 15%). Regional C (RS) plots clearly demonstrated co-existent ventral
      overdistension and dorsal recruitment, particularly during PEEP increments;
      whereas during PEEP decrements, peak C (RS(reg)) values showed considerable
      interregional concordance [e.g. peak C (RS(reg)) in the lavaged left lung;
      ventral: 0.017 +/- 0.0036; medial: 0.016 +/- 0.0054; dorsal: 0.017 +/- 0.0073
      cmH2O-1; P = 0.98, analysis of variance (ANOVA)]. CONCLUSIONS: After lung
      recruitment, a PEEP level can be identified by EIT at which tidal ventilation is
      uniformly distributed, with associated concordance in compliance between lung
      regions. Bedside monitoring of regional tidal ventilation and compliance using
      EIT may thus aid in PEEP selection.

PMID- 20689921
TI  - Performance of noninvasive ventilation algorithms on ICU ventilators during
      pressure support: a clinical study.
AB  - OBJECTIVE: To evaluate the impact of noninvasive ventilation (NIV) algorithms
      available on intensive care unit ventilators on the incidence of patient
      ventilator asynchrony in patients receiving NIV for acute respiratory failure.
      DESIGN: Prospective multicenter randomized cross-over study. SETTING: Intensive
      care units in three university hospitals. METHODS: Patients consecutively
      admitted to the ICU and treated by NIV with an ICU ventilator were included.
      Airway pressure, flow and surface diaphragmatic electromyography were recorded
      continuously during two 30-min periods, with the NIV (NIV+) or without the NIV
      algorithm (NIV0). Asynchrony events, the asynchrony index (AI) and a specific
      asynchrony index influenced by leaks (AIleaks) were determined from tracing
      analysis. RESULTS: Sixty-five patients were included. With and without the NIV
      algorithm, respectively, auto-triggering was present in 14 (22%) and 10 (15%)
      patients, ineffective breaths in 15 (23%) and 5 (8%) (p = 0.004), late cycling in
      11 (17%) and 5 (8%) (p = 0.003), premature cycling in 22 (34%) and 21 (32%), and
      double triggering in 3 (5%) and 6 (9%). The mean number of asynchronies
      influenced by leaks was significantly reduced by the NIV algorithm (p < 0.05). A
      significant correlation was found between the magnitude of leaks and AIleaks when
      the NIV algorithm was not activated (p = 0.03). The global AI remained unchanged,
      mainly because on some ventilators with the NIV algorithm premature cycling
      occurs. CONCLUSION: In acute respiratory failure, NIV algorithms provided by ICU
      ventilators can reduce the incidence of asynchronies because of leaks, thus
      confirming bench test results, but some of these algorithms can generate
      premature cycling.

PMID- 20689922
TI  - Gas distribution in a two-compartment model ventilated in high-frequency
      percussive and pressure-controlled modes.
AB  - PURPOSE: To demonstrate in a two-compartment heterogeneous mechanical model of
      the lung how different loads applied to one compartment, while the other is kept
      constant, would modify gas distribution between the two pathways under high
      frequency percussive ventilation (HFPV). Additionally, these results were
      compared with those generated in the same model by pressure-controlled
      ventilation (PCV). METHODS: Analysis was based on a Siemens lung simulator,
      representing a fixed branch of the system with an elastance equal to 45 cmH(2)O/L
      and a resistance of 20 cmH(2)O/L/s, and a single-compartment lung simulator,
      representing a variable pathway of the model, presenting three elastic loads
      varying between 35 and 85 cmH(2)O/L and three resistive loads varying between 5
      and 50 cmH(2)O/L/s. Each simulator represented one compartment of the model
      connected to a central airway that was ventilated with either a volumetric
      diffusive respirator (VDR-4; Percussionaire Corporation, Sandpoint, ID, USA) or a
      Siemens Servo 900c ventilator. Flow and pressures were measured in each branch of
      the model under nine conditions representing the combinations of three elastic
      and three resistive loads (variable branch) while the loads in the other pathway
      were kept constant. RESULTS: HFPV was able to avoid hyperinflation and reduce
      tidal volume in a bicompartmental heterogeneous lung model. Under HFPV, gas
      distribution between the two compartments was not constrained by their time
      constants. PCV yielded gas distribution as determined by the time constant of
      each compartment. CONCLUSIONS: HFPV accommodated volume distribution without
      overinflating compartments with low time constants, thus possibly presenting a
      potential protective behavior in mechanically heterogeneous lungs.

PMID- 20689923
TI  - Beware of etomidate and cricoid pressure during rapid sequence induction.

PMID- 20689925
TI  - Refractory agitation as a marker for pediatric delirium in very young infants at
      a pediatric intensive care unit.

PMID- 20689926
TI  - Inability to obtain deferred consent due to early death in emergency research:
      effect on validity of clinical trial results.
AB  - PURPOSE: To illustrate the impact on the validity of trial results due to
      excluding patients from a randomized controlled trial for whom no deferred
      consent could be obtained after randomization because study procedures had
      already been finished. METHODS: The unadjusted and adjusted primary outcome
      measures of a recent randomized controlled multicentre study in the field of
      intensive care medicine were compared, including (n = 348) or excluding (n = 289)
      patients with missing deferred consent. RESULTS: Thirty-nine patients (11%) died
      early, before the patient or his/her proxy could be approached and consent be
      obtained. In another 20 patients (6%), it was not possible to inform proxies and
      ask consent within the period of study procedures. A significant treatment effect
      (p = 0.006) in the adjusted analysis became non-significant (p = 0.35) when the
      patients with missing deferred consent were excluded. CONCLUSIONS: Exclusion of
      patients without obtained deferred consent can reduce statistical power,
      introduce selection bias, make randomization asymmetrical, decrease external
      validity and thereby jeopardize study results. This may have implications for
      emergency research in various disciplines.

PMID- 20689924
TI  - Propensity scores in intensive care and anaesthesiology literature: a systematic
      review.
AB  - INTRODUCTION: Propensity score methods have been increasingly used in the last 10
      years. However, the practical use of the propensity score (PS) has been reported
      as heterogeneous in several papers reviewing the use of propensity scores and
      giving some advice. No precedent work has focused on the specific application of
      PS in intensive care and anaesthesiology literature. OBJECTIVES: After a brief
      development of the theory of propensity score, to assess the use and the quality
      of reporting of PS studies in intensive care and anaesthesiology, and to evaluate
      how past reviews have influenced the quality of the reporting. STUDY DESIGN AND
      SETTING: Forty-seven articles published between 2006 and 2009 in the intensive
      care and anaesthesiology literature were evaluated. We extracted the
      characteristics of the report, the type of analysis, the details of matching
      procedures, the number of patients in treated and control groups, and the number
      of covariates included in the PS models. RESULTS: Of the 47 articles reviewed, 26
      used matching on PS, 12 used stratification on PS and 9 used adjustment on PS.
      The method used was reported in 81% of the articles, and the choice to conduct a
      paired analysis or not was reported in only 15%. The comparison with the
      previously published reviews showed little improvement in reporting in the last
      few years. CONCLUSION: The quality of reporting propensity scores in intensive
      care and anaesthesiology literature should be improved. We provide some
      recommendations to the investigators in order to improve the reporting of PS
      analyses.

PMID- 20689927
TI  - Reorganising the pandemic triage processes to ethically maximise individuals'
      best interests.
AB  - PURPOSE: To provide a revised definition, process and purpose of triage to
      maximise the number of patients receiving intensive care during a crisis.
      METHODS: Based on the ethical principle of virtue ethics and the underlying goal
      of providing individual patients with treatment according to their best
      interests, the methodology of triage is reassessed and revised. RESULTS: The
      decision making processes regarding treatment decisions during a pandemic are
      redefined and new methods of intensive care provision recommended as well as
      recommending the use of a 'ranking' system for patients excluded from intensive
      care, defining the role of non-intensive care specialists, and applying two types
      of triage as 'organisational triage' and 'treatment triage' based on the demand
      for intensive care. CONCLUSION: Using a different underlying ethical basis upon
      which to plan for a pandemic crisis could maximise the number of patients
      receiving intensive care based on individual patients' best interests.

PMID- 20689928
TI  - Patients' prediction of extubation success.
AB  - PURPOSE: The spontaneous breathing trial (SBT)-relying on objective criteria
      assessed by the clinician-is the major diagnostic tool to determine if patients
      can be successfully extubated. However, little is known regarding the patient's
      subjective perception of autonomous breathing. METHODS: We performed a
      prospective observational study in 211 mechanically ventilated adult patients
      successfully completing a SBT. Patients were randomly assigned to be interviewed
      during this trial regarding their prediction of extubation success. We compared
      post-extubation outcomes in three patient groups: patients confident (confidents;
      n = 115) or not (non-confidents; n = 38) of their extubation success and patients
      not subjected to interview (control group; n = 58). RESULTS: Extubation success
      was more frequent in confidents than in non-confidents (90 vs. 45%; p <
      0.001/positive likelihood ratio = 2.00) or in the control group (90 vs. 78%; p =
      0.04). On the contrary, extubation failure was more common in non-confidents than
      in confidents (55 vs. 10%; p < 0.001/negative likelihood ratio = 0.19). Logistic
      regression analysis showed that extubation success was associated with patient's
      prediction [OR (95% CI): 9.2 (3.74-22.42) for confidents vs.non-confidents] as
      well as to age [0.72 (0.66-0.78) for age 75 vs. 65 and 1.31 (1.28-1.51) for age
      55 vs. 65]. CONCLUSIONS: Our data suggest that at the end of a sustained SBT,
      extubation success might be correlated to the patients' subjective perception of
      autonomous breathing. The results of this study should be confirmed by a large
      multicenter trial.

PMID- 20689929
TI  - Toll-like receptors 2 and 4: initiators of non-septic inflammation in critical
      care medicine?
AB  - PURPOSE: Although the role of Toll-like receptors (TLRs) in bacterial infection
      and sepsis is well characterized, recent studies have also shown that TLR4 and
      TLR2 can play an important role in contributing to acute inflammatory processes
      and organ dysfunction in settings in which LPS or other bacterial products are
      not present. This review presents not only insights into pathophysiologic
      mechanisms that contribute to organ dysfunction and outcome in critical illness,
      but also direct therapeutic approaches to ameliorating such TLR-mediated
      responses that may potentially be of clinical benefit in critically ill patients.
      METHOD: Literature review of the role of TLR4 and TLR2 in sterile inflammation
      relevant to critical care medicine using PubMed search, including original papers
      in English from 1990 to 2010. CONCLUSION: There is increasing evidence that TLR4
      and TLR2 are not only receptors for bacterial products, but also can be activated
      through other mechanisms relevant to the pathophysiology of critical illnesses.
      There is evidence that TLR4 and TLR2 are involved in ischemia-reperfusion injury
      and trauma where Gram-negative or Gram-positive bacteria are not detectible in
      the circulation or local organ sites, such as the lungs. In these settings TLRs
      can transduce other proinflammatory signals and thereby contribute to cellular
      activation leading to acute lung injury and other organ system dysfunction. The
      consequences of TLR4 and TLR2 activation through reactive oxygen species (ROS),
      heat shock proteins, and other non-LPS dependent mechanisms may be different from
      those associated with binding of the membrane component of bacteria to TLR4 or
      TLR2 and may produce different signatures of gene activation and release of
      proinflammatory mediators.

PMID- 20689930
TI  - Autoregulation of ventilation with neurally adjusted ventilatory assist on
      extracorporeal lung support.
AB  - PURPOSE: Extracorporeal membrane oxygenation (ECMO) can support oxygenation and
      carbon dioxide elimination in severe lung failure. Usually it is accompanied by
      controlled mechanical ventilation. Neurally adjusted ventilatory assist (NAVA) is
      a new mode of ventilation triggered by the diaphragmatic electrical activity and
      controlled by the patient's respiratory centre, which may allow a close
      interaction between ventilation and extracorporeal perfusion. This pilot study
      intended to measure the physiologic ventilatory response in patients with severe
      lung failure treated with ECMO and NAVA. We hypothesized that the combination of
      both methods could automatically provide a protective ventilation with optimized
      blood gases. METHODS: We report a case series of six patients treated with ECMO
      for severe lung failure. In the recovery phase of the disease, patients were
      ventilated with NAVA and ventilatory response and gas exchange parameters were
      measured under different sweep gas flows and temporarily inactivated ECMO.
      RESULTS: Tidal volumes on ECMO ranged between 2 and 5 ml/kg predicted body weight
      and increased up to 8 ml/kg with inactivated ECMO. Peak inspiratory pressure
      reached 19-29 cmH(2)O with active, and 21-45 cmH(2)O with inactivated ECMO.
      Ventilatory response to decreased sweep gas flow was rapid, and patients
      immediately regulated PaCO(2) tightly towards a physiological pH value. Increase
      in minute ventilation was a result of increased breathing frequency and tidal
      volumes, and protective ventilation was only abandoned if pH control was not
      achieved. CONCLUSIONS: With NAVA ventilatory response to decreased ECMO sweep gas
      flow was rapid, and patients immediately regulated PaCO(2) tightly towards a
      physiological pH value. Therefore, combination of NAVA and ECMO may permit a
      closed-loop ventilation with automated protective ventilation.

PMID- 20689931
TI  - Reproduction of inert gas and oxygenation data: a comparison of the MIGET and a
      simple model of pulmonary gas exchange.
AB  - PURPOSE: The multiple inert gas elimination technique (MIGET) is the reference
      method for evaluating pulmonary gas exchange. MIGET includes a complex
      experimental method and mathematical model, and has not been used routinely in
      clinical practice. A simpler mathematical model has been proposed, and was shown
      previously to fit inert gas data from oleic acid damage. This paper explores the
      capability of this simple model to describe more complex damage, and to calculate
      oxygenation data upon changing the inspired oxygen fraction (FIO(2)), comparing
      these results with those obtained using MIGET. METHODS: The comparison of
      oxygenation was done at different ventilator settings and at varying values of
      FIO(2) in order to mimic the clinical conditions that occur in the intensive care
      unit. RESULTS: The simple model describes inert gas data from heterogeneous lung
      damage within measurement noise. Model simulations performed using the MIGET and
      the simple model are comparable, the MIGET model simulating partial pressure of
      oxygen (PaO(2)) values on average 0.22 +/- 0.59 kPa (+/- SD) higher than the
      simple model. Model simulations are also accurate with a difference between model
      simulated and measured values of PaO(2) of 0.33 +/- 1.48 kPa (+/- SD) for the
      MIGET model and 0.12 +/- 1.33 kPa (+/- SD) for the simple model. This
      comparability and accuracy was similar over different ventilator settings.
      CONCLUSIONS: The simple model provides a description of lung damage and arterial
      oxygenation which is comparable to the MIGET, calculating PaO(2) with acceptable
      accuracy and precision over the clinically relevant range of PaO(2), and for
      different values of FIO(2), positive end-expiratory pressure (PEEP), and
      inspiratory-to-expiratory ratio (I:E).

PMID- 20689932
TI  - Low and "supranormal" central venous oxygen saturation and markers of tissue
      hypoxia in cardiac surgery patients: a prospective observational study.
AB  - PURPOSE: To characterize incidence of low, normal and "supranormal" central
      venous oxygen saturation (ScvO(2)) and the relation to markers of tissue hypoxia,
      course and outcome in cardiac surgery patients. METHODS: Prospective,
      observational study in a university multidisciplinary 50-bed intensive care unit
      including 205 consecutive patients undergoing elective cardiac surgery. Data were
      split into training and test data sets and subjected to 50 replications of
      fivefold cross-validation to estimate lower and upper bounds of ScvO(2)
      indicative of impaired tissue oxygenation. RESULTS: Both low (<= 60.8%) and
      supranormal (>= 77.4%) ScvO(2) were associated with an unfavorable course, while
      the logistic EuroSCORE for risk adjustment was comparable between groups.
      Incidences of abnormal ScvO(2) were 13.2% low and 30.7% supranormal. Patients
      with low ScvO(2) and an uneventful course initially presented with normal lactate
      levels, whereas patients with supranormal ScvO(2) displayed consistently higher
      serum lactate levels. High ScvO(2) values were associated with the use of beta
      mimetics and signs of systemic inflammation. Mortality rates were comparable for
      patient populations presenting either low (14.8%) or supranormal ScvO(2) (7.9%)
      and higher than normals (0%, p < 0.001). Lactate was comparably increased in
      patients that ultimately died, irrespective whether they had low or supranormal
      ScvO(2) values. In contrast, neither low nor supranormal ScvO(2) was associated
      with altered gastric pCO(2.) CONCLUSIONS: High ScvO(2) is an under-recognized
      warning sign for impaired tissue oxygenation in the peri-operative period.
      Including values >= 77.4% as 'normal' impaired performance of ScvO(2) monitoring
      to predict a complicated perioperative course.

PMID- 20689933
TI  - Comparison of two utility instruments, the EQ-5D and the 15D, in the critical
      care setting.
AB  - PURPOSE: Reliable measures are required for proper cost-utility analysis after
      critical care. No gold standard is available, but the EQ-5D health-related
      quality of life instrument (HRQoL) has been proposed. Our aim was to compare the
      EQ-5D with another utility measure, the 15D, after critical illness. METHODS: A
      total of 929 patients filled in both the EQ-5D and 15D HRQoL instruments 6 and 12
      months after treatment at an intensive care or high-dependency unit. The
      difference in the medians and distributions of the scores of the instruments was
      tested with Wilcoxon signed-rank test and their association with Spearman rank
      correlation. Discriminatory power was compared by the ceiling effect and
      agreement between the instruments regarding the direction of the minimal
      clinically important change in the HRQoL scores between 6 and 12 months was
      tested with the McNemar-Bowker test and Cohen's kappa. RESULTS: The utility
      scores produced by the instruments and their distributions were different.
      Agreement between the instruments was only moderate. The 15D appeared more
      sensitive than the EQ-5D both in terms of discriminatory power and responsiveness
      to clinically important change. CONCLUSION: The agreement between the two utility
      measures was only moderate. The choice of the instrument may have a substantial
      effect on cost-utility results. Our results suggest that the 15D performs well
      after critical illness, but further large cohort studies comparing different
      utility instruments in this patient population are warranted before the gold
      standard for utility measurement can be announced.

PMID- 20689934
TI  - Statistical analysis plan of PROWESS SHOCK study.

PMID- 20689935
TI  - Impaired microvascular perfusion in sepsis requires activated coagulation and P
      selectin-mediated platelet adhesion in capillaries.
AB  - PURPOSE: Impaired microvascular perfusion in sepsis is not treated effectively
      because its mechanism is unknown. Since inflammatory and coagulation pathways
      cross-activate, we tested if stoppage of blood flow in septic capillaries is due
      to oxidant-dependent adhesion of platelets in these microvessels. METHODS: Sepsis
      was induced in wild type, eNOS(-/-), iNOS(-/-), and gp91phox(-/-) mice (n = 14
      199) by injection of feces into the peritoneum. Platelet adhesion, fibrin
      deposition, and blood flow stoppage in capillaries of hindlimb skeletal muscle
      were assessed by intravital microscopy. Prophylactic treatments at the onset of
      sepsis were intravenous injection of platelet-depleting antibody, P-selectin
      blocking antibody, ascorbate, or antithrombin. Therapeutic treatments (delayed
      until 6 h) were injection of ascorbate or the glycoprotein IIb/IIIa inhibitor
      eptifibatide, or local superfusion of the muscle with NOS cofactor
      tetrahydrobiopterin or NO donor S-nitroso-N-acetylpenicillamine (SNAP). RESULTS:
      Sepsis at 6-7 h markedly increased the number of stopped-flow capillaries and the
      occurrence of platelet adhesion and fibrin deposition in these capillaries.
      Platelet depletion, iNOS and gp91phox deficiencies, P-selectin blockade,
      antithrombin, or prophylactic ascorbate prevented, whereas delayed ascorbate,
      eptifibatide, tetrahydrobiopterin, or SNAP reversed, septic platelet adhesion
      and/or flow stoppage. The reversals by ascorbate and tetrahydrobiopterin were
      absent in eNOS(-/-) mice. Platelet adhesion predicted 90% of capillary flow
      stoppage. CONCLUSION: Impaired perfusion and/or platelet adhesion in septic
      capillaries requires NADPH oxidase, iNOS, P-selectin, and activated coagulation,
      and is inhibited by intravenous administration of ascorbate and by local
      superfusion of tetrahydrobiopterin and NO. Reversal of flow stoppage by ascorbate
      and tetrahydrobiopterin may depend on local eNOS-derived NO which dislodges
      platelets from the capillary wall.

PMID- 20689936
TI  - Intensivists managing end-of-life care: dwarfs without giants' shoulders to stand
      upon.

PMID- 20689937
TI  - What to do when a competent ICU patient does not want to live anymore but is
      dependent on life-sustaining treatment? Experience from The Netherlands.
AB  - If patients on the intensive care unit (ICU) are awake and life-sustaining
      treatment is suspended because of the patients' request, because of recovering
      from the disease, or because independence from organ function supportive or
      replacement therapy outside the ICU can no longer be achieved, these patients can
      suffer before they inevitably die. In The Netherlands, two scenarios are possible
      for these patients: (1) deep palliative (terminal) sedation through ongoing
      administration of barbiturates or benzodiazepines before withdrawal of treatment,
      or (2) deliberate termination of life (euthanasia) before termination of
      treatment. In this article we describe two awake patients who asked for
      withdrawal of life-sustaining measures, but who were dependent on mechanical
      ventilation. We discuss the doctrine of double effect in relation to palliative
      sedation on the ICU. Administration of sedatives and analgesics before withdrawal
      of treatment is seen as normal palliative care. We conclude that the doctrine of
      the double effect is not applicable in this situation, and mentioning it
      criminalised the practice unnecessarily and wrongfully.

PMID- 20689938
TI  - Depression-like behavior and mechanical allodynia are reduced by bis selenide
      treatment in mice with chronic constriction injury: a comparison with fluoxetine,
      amitriptyline, and bupropion.
AB  - RATIONALE: Neuropathic pain is associated with significant co-morbidities,
      including depression, which impact considerably on the overall patient
      experience. Pain co-morbidity symptoms are rarely assessed in animal models of
      neuropathic pain. Neuropathic pain is characterized by hyperexcitability within
      nociceptive pathways and remains difficult to treat with standard analgesics.
      OBJECTIVES: The present study determined the effect of bis selenide and
      conventional antidepressants (fluoxetine, amitriptyline, and bupropion) on
      neuropathic pain using mechanical allodynic and on depressive-like behavior.
      METHODS: Male mice were subjected to chronic constriction injury (CCI) or sham
      surgery and were assessed on day 14 after operation. Mice received oral treatment
      with bis selenide (1-5 mg/kg), fluoxetine, amitriptyline, or bupropion (10-30
      mg/kg). The response frequency to mechanical allodynia in mice was measured with
      von Frey hairs. Mice were evaluated in the forced swimming test (FST) test for
      depression-like behavior. RESULTS: The CCI procedure produced mechanical
      allodynia and increased depressive-like behavior in the FST. All of the drugs
      produced antiallodynic effects in CCI mice and produced antidepressant effects in
      control mice without altering locomotor activity. In CCI animals, however, only
      the amitriptyline and bis selenide treatments significantly reduced immobility in
      the FST. CONCLUSION: These data demonstrate an important dissociation between the
      antiallodynic and antidepressant effects in mice when tested in a model of
      neuropathic pain. Depressive behavior in CCI mice was reversed by bis selenide
      and amitriptyline but not by the conventional antidepressants fluoxetine and
      buproprion. Bis selenide was more potent than the other drugs tested for
      antidepressant-like and antiallodynic effects in mice.

PMID- 20689939
TI  - Trait-like impulsivity does not predict escalation of heroin self-administration
      in the rat.
AB  - RATIONALE: The neural and psychological mechanisms underlying vulnerability to
      drug addiction are poorly understood. Although a number of animal models have
      been developed to investigate vulnerability to stimulant addiction, few have
      considered how vulnerability traits such as impulsivity predict hallmark features
      of heroin addiction including the escalation of drug intake and increased
      propensity for relapse following protracted abstinence. OBJECTIVE: The aim of
      this study was to investigate whether high impulsivity in rats predicts the
      propensity to escalate intravenous heroin self-administration and to relapse
      following an extended withdrawal period from heroin. METHODS: High (HI)- and low
      (LI)-impulsive rats, defined by the extent of premature responding on the 5
      choice serial reaction time test (5-CSRTT), were catheterized and allowed to self
      administer heroin (40 MUg/100 MUl/infusion). After 5 days of short access (1
      h/day) to heroin, rats were then given extended (6 h/day) access to heroin for 18
      consecutive days. RESULTS: High impulsivity predicted neither a greater tendency
      to acquire heroin SA nor an increased escalation of heroin self-administration.
      Moreover, high impulsivity was not associated with an increased propensity to
      relapse after protracted withdrawal from heroin. Nevertheless, marked inter
      individual differences in the escalation of heroin self-administration were
      observed. CONCLUSIONS: Although high impulsivity on the 5-CSRTT has been shown to
      predict loss of control over cocaine intake, this does not generalize to a loss
      of control over heroin self-administration. These findings suggest important
      distinctions in vulnerability mechanisms underlying cocaine and heroin addiction
      with trait-like impulsivity playing a role in stimulant but not opiate addiction.

PMID- 20689940
TI  - GABA(A) rho receptor mechanisms in the rat amygdala and its role in the
      modulation of fear and anxiety.
AB  - RATIONALE: Accumulating evidence for the presence of GABA(A) rho receptors within
      the amygdala which differ from other members of the GABA(A) receptor family in
      both subunit composition and functional properties has been recently obtained.
      OBJECTIVES: This work was conducted to study whether GABA(A) rho receptors may
      have a putative role in the amygdaloid modulation of fear and anxiety. RESULTS:
      It was found that the bilateral intra-amygdaloid administration (6-240 pmol/side)
      of (1,2,5,6-tetrahydropyridine-4-yl)methylphosphinic acid, a selective GABA(A)
      rho receptor antagonist, reduced dose-dependently the exploration of the open
      arms of the elevated plus-maze without affecting locomotion and increased the
      plasma levels of corticosterone. In contrast, bicuculline in the dose range used
      (1.8-60 pmol/side) induced seizures, but had no effects on the exploration of the
      maze. CONCLUSIONS: It is suggested that GABA(A) rho receptors may have a role in
      the amygdaloid modulation of fear and anxiety.

PMID- 20689942
TI  - Clinical and neurocognitive changes with modafinil in obsessive-compulsive
      disorder: a case report.

PMID- 20689941
TI  - Differential effects of allopregnanolone on the escalation of cocaine self
      administration and sucrose intake in female rats.
AB  - RATIONALE: Evidence suggests that the progesterone metabolite allopregnanolone
      (ALLO) decreases cocaine seeking in animal models of relapse. OBJECTIVE: The
      purpose of this study was to examine the effects of ALLO on an animal model of
      cocaine and sucrose bingeing (escalation). Allopregnanolone's effects on
      yohimbine-induced sucrose intake were also examined. In a separate group of
      animals, dose interactions between ALLO and cocaine were examined with an
      abbreviated procedure, a short access progressive ratio (PR) schedule for cocaine
      reinforcement. METHODS: Female rats were treated with ALLO (15 mg/kg, s.c.) or
      vehicle (VEH) and trained to lever press for cocaine infusions (0.4 mg/kg) under
      an extended-access procedure. In a separate condition, other ALLO- and VEH
      treated female rats self-administered orally delivered liquid sucrose.
      Allopregnanolone and VEH treatment was then discountinued and the sucrose
      maintained rats were administered priming injections of saline, yohimbine, or
      yohimbine + ALLO. For the PR condition, rats were first treated with VEH until
      reaching stability at four doses of cocaine (0.2, 0.4, 0.8, and 1.6 mg/kg in
      mixed order). Subsequently, rats re-established their baseline cocaine intake at
      the four cocaine doses following treatment with each of two counterbalanced doses
      of ALLO (15 and 30 mg/kg). RESULTS: ALLO significantly blocked the escalation of
      cocaine self-administration but did not reliably affect intake of sucrose under a
      similar condition or affect cocaine intake at several doses under a PR schedule.
      Yohimbine significantly increased sucrose intake while ALLO failed to attenuate
      this increase. CONCLUSION: These findings indicate that ALLO protects against
      binge-like patterns of cocaine intake but does not reduce sugar intake that is
      acutely increased by yohimbine in females.

PMID- 20689943
TI  - Adverse drug reactions in internal medicine units and associated risk factors.
AB  - OBJECTIVES: This study was designed to assess the prevalence of adverse drug
      reactions (ADRs) in the internal medicine wards of two teaching hospitals,
      identify the most common ADRs, the principal medications involved, and determine
      the risk factors implicated in the occurrence of such ADRs. METHODS: All
      admissions over 10 weeks were followed prospectively using an intensive drug
      surveillance method to identify ADRs. Clinical laboratory data, the drug
      prescribed, and ADRs were taken into consideration. Status of nutrition, liver
      and kidney function at admission, and ADR time were determined. In order to
      assess drug interactions a software package was used. RESULTS: A total of 405
      patients were evaluated, 126 patients (31%) had 128 ADRs, 122 ADRs occurred
      during hospitalization. Two ADR-related deaths were observed during the study.
      Reactions affecting the gastrointestinal tract, skin, and hematological system
      were among the most frequent ADRs. For ADRs observed during admission predictors
      of its occurrence in a multivariate regression model were: OR (95% CI); more than
      12 days' hospitalization: 2.11(1.27-3.47), any drug interaction: 9.33 (5.12-17)
      and acute change in estimated glomerular filtration rate over admission >20%:
      2.46 (1.45-4.2). Worsening of renal function or drug interaction was observed in
      nine of the ten ADRs. Age, sex, nutrition, and number of drugs used were not
      related to ADRs. CONCLUSION: A significant prevalence of ADRs was found among
      hospitalized patients. Duration of hospital admission, changes in renal status
      during hospitalization and drug interactions seem to be important risk factors
      for ADRs.

PMID- 20689944
TI  - Multi-modality imaging findings of disseminated juvenile xanthogranuloma with
      renal involvement in an infant.
AB  - Juvenile xanthogranuloma is a non-Langerhans cell histiocytosis commonly
      presenting as a solitary cutaneous lesion. A small subset of patients have
      visceral involvement. Renal involvement is rare. Several case reports have
      highlighted solitary extracutaneous lesions. Few reports describe imaging
      findings in multiple visceral organs. We describe a unique case of disseminated
      JXG with involvement of the kidney as well as other visceral organs including the
      liver, spleen and lungs.

PMID- 20689945
TI  - Role of plain abdominal radiographs in predicting type of congenital pouch colon.
AB  - BACKGROUND: Congenital pouch colon (CPC) is a rare form of high ano-rectal
      malformation (ARM) in which part of or the entire colon is replaced by a pouch
      with a fistula to the genito-urinary tract. According to the Saxena-Mathur
      classification CPC is divided into five types. Although plain abdominal
      radiographs are taken in infants with suspicion of CPC to detect large dilatation
      of the pouch, the determination of the type of CPC is made during surgical
      exploration. Since large variations in the length of normal colon are present in
      the various types, management strategy options can be determined only at the time
      of surgery. OBJECTIVE: The aim of this study was to review abdominal radiographs
      of children with congenital pouch colon (CPC) and evaluate their value in
      determining the type of CPC prior to surgical exploration to assist pre-operative
      planning. MATERIALS AND METHODS: Over a 12-year period (1995-2007), CPC was
      documented in 80 children (52 boys and 28 girls, age range 1 day-9 years, median
      2.4 days) and retrospective analysis of plain abdominal radiographs of 77
      children at the time of presentation was performed. Radiographic findings were
      correlated with surgical findings. RESULTS: Of 77 children, 5 were excluded from
      the study since the pouch colon was perforated. The direction of the pouch apex
      was correlated with surgical findings to determine the CPC type (P<0.0001, Fisher
      exact test). Type 1 (17/18) and type 2 CPC (18/18) were characterized by a single
      large pouch with the apex positioned in the left hypochondrium. In type 3 CPC
      (2/2) the pouch apex was directed towards the right hypochondrium. In type 4 CPC
      the apex of the pouch was directed towards the right hypochondrium (28/33);
      however in 5 children it was towards the left hypochondrium. In type 5 CPC (n=1)
      the radiograph was inconclusive. CONCLUSION: Plain abdominal radiographs have a
      predictive value in determining the type of CPC and obviating the need for an
      invertogram.

PMID- 20689946
TI  - Feasibility of 3-T MRI for the evaluation of Crohn disease in children.
AB  - BACKGROUND: Crohn disease (CD) is a chronic inflammatory bowel disease that can
      affect any part of the gastrointestinal tract from the oral cavity to the anal
      canal. It occurs in all ages and is a significant cause for morbidity in
      children. Interest in MRI evaluation of CD has increased because of the concern
      regarding cumulative radiation dose from contrast fluoroscopic studies and CT.
      Several reports have demonstrated MRI to be a useful technique for CD. Most of
      these studies were performed at 1.5-T field strength. Imaging at a higher field
      strength, with a greater signal-to-noise ratio, has the potential of reducing
      scan times and increasing the resolution. However, there is a concurrent increase
      in artefacts, and these can be pronounced with abdominal imaging at 3 T.
      OBJECTIVE: To determine the feasibility of 3-T MRI for CD in children and to
      assess the value of different sequences and the effect of artefacts that could
      potentially limit the role of bowel MR imaging at higher field strengths.
      MATERIALS AND METHODS: A retrospective study of 46 children with biopsy-proven CD
      (ages 8-19 years, 53% boys) was performed. Sixty-eight consecutive MRI studies
      were performed on a 3-T scanner between 2005 and 2007; 42 of the abdomen (62%)
      and 26 of the pelvis/perineum (38%). Sorbitol was administered for the abdominal
      studies; orally for 36/42 (86%) studies and via a naso-jejunal (NJ) tube for 6/42
      (14%) studies. For the abdomen, T2-W half-fourier acquisition single-shot turbo
      spin-echo (T2-W HASTE), true steady-state free precession (true FISP), pre
      contrast and contrast-enhanced (CE) T1-volume interpolated gradient-echo (T1-W
      VIBE) and CE T1-W fast low-angle shot (T1-W FLASH) sequences were performed. For
      the perianal and pelvic assessment, fat-saturated T2-W turbo spin-echo (TSE), pre
      contrast and CE T1-W FLASH or VIBE sequences were performed. The sequences were
      scored for diagnostic quality by two paediatric radiologists for visualisation of
      the bowel wall, whether normal or pathological and the visualization of extra
      intestinal manifestations. The effects of distension, susceptibility artefact and
      motion were assessed. RESULTS: Six (14%) abdominal MRI studies were normal.
      Thirty-six (86%) were abnormal with good correlation with endoscopic findings.
      The pelvic and perianal MRI studies were all abnormal (26/26, 100%) with good
      correlation with proctoscopy and examination under anaesthesia. All the sequences
      had high average scores (greater than or close to 3), except true FISP with a
      score of 2.4. The score was greatest in those who had NJ administration of
      sorbitol; however, satisfactory distension was also possible with oral
      administration of contrast. True FISP was the sequence most affected by a
      combination of suboptimal distension and artefact from colonic contents. With
      adequate distension, true FISP image quality improved remarkably. The overall
      score of this sequence was satisfactory in the absence of susceptibility and
      movement artefact. CONCLUSION: With appropriate attention to technique, with
      optimal distension and control of movement, high-quality, 3-T assessment of the
      abdomen, pelvis and perineum is possible. All sequences used at 1.5 T can be used
      at 3 T, however true FISP was the most prone to artefact.

PMID- 20689947
TI  - Asynchronous neuro-osseous growth in adolescent idiopathic scoliosis--MRI-based
      research.
AB  - Adolescent idiopathic scoliosis (AIS) is a common worldwide problem and has been
      treated for many decades; however, there still remain uncertain areas about this
      disorder. Its involvement and impact on different parts of the human body remain
      underestimated due to lack of technology in imaging for objective assessment in
      the past. The advances in imaging technique and image analysis technology have
      provided a novel approach for the understanding of the phenotypic presentation of
      neuro-osseous changes in AIS patients as compared with normal controls. This
      review is the summary of morphological assessment of the skeletal and nervous
      systems in girls with AIS based on MRI. Girls with AIS are found to have
      morphological differences in multiple areas including the vertebral column,
      spinal cord, skull and brain when compared with age- and sex-matched normal
      controls. Taken together, the abnormalities in the skeletal system and nervous
      system of AIS are likely to be inter-related and reflect a systemic process of
      asynchronous neuro-osseous growth. The current knowledge about the anatomical
      changes in AIS has important implications with respect to the understanding of
      fundamental pathomechanical processes involved in the evolution of the scoliotic
      deformity.

PMID- 20689948
TI  - Reversible cytotoxic oedema in the splenium of the corpus callosum related to
      tetracycline therapy.
AB  - We report a symptomatic girl with reversible circumscribed cytotoxic oedema in
      the splenium of the corpus callosum (CC) that occurred, to our knowledge, for the
      first time in relation to tetracycline treatment. After stopping tetracycline
      therapy the girl recovered completely and the CC lesion, clearly visible on
      diffusion-weighted MR imaging (DWI), disappeared. Reversible circumscribed
      cytotoxic oedema (CCO) of the splenium of the CC is a well-defined entity that is
      found to be associated with administration of antiepileptic drugs, alterations in
      therapy using arginin-vasopressin and metronidazole or infections with influenza
      and rotavirus. CCO of splenium of the CC is clearly visible on DWI, shows no
      enhancement after administration of contrast medium and is completely reversible
      in most cases.

PMID- 20689949
TI  - Postmortem MRI of bladder agenesis.
AB  - We report a 35-week preterm neonate with bladder agenesis and bilateral
      dysplastic kidneys. A suprapubic catheter was inadvertently inserted into one of
      the larger inferior cysts of the left dysplastic kidney. A postmortem MRI scan
      was performed with the findings being confirmed on autopsy. We are unaware of
      another postmortem MRI study demonstrating bladder agenesis.

PMID- 20689950
TI  - Methods in mammalian cell line engineering: from random mutagenesis to sequence
      specific approaches.
AB  - Due to the increasing demand for recombinant proteins, the interest in mammalian
      cell culture, especially of Chinese hamster ovary cells, grows rapidly. This is
      accompanied by the desire to improve cell lines in order to achieve higher titers
      and a better product quality. Until recently, most cell line development
      procedures were based on random integration and gene amplification, but several
      methods for targeted genetic modification of cells have been developed. Some of
      those are homologous recombination, RNA interference and zinc-finger nucleases.
      Especially the latter two have evolved considerably and will soon become a
      standard for cell line engineering in research and industrial application. This
      review presents an overview of established as well as new and promising
      techniques for targeted genetic modification of mammalian cells.

PMID- 20689951
TI  - Scale-up of Baeyer-Villiger monooxygenase-catalyzed synthesis of enantiopure
      compounds.
AB  - Several Baeyer-Villiger monooxygenases converting a wide spectrum of substrates
      have been discovered, cloned, and characterized throughout the last few years.
      Still, only a few of them are applicable for large-scale conversion predominantly
      due to their sensitivity towards high substrate and/or product concentrations.
      The recently cloned and characterized 4-hydroxyacetophenone monooxygenase from
      Pseudomonas putida JD1 shows excellent enantioselectivity towards 3-phenyl-2
      butanone with E > 100 but is inhibited by concentrations >10 mM of both substrate
      and product. This obstacle could be circumvented by in situ substrate feed and
      product removal using a hydrophobic Lewatit(r) adsorbent resin. Thus, the
      concentration of 3-phenyl-2-butanone could be increased from 1.4 to >26 mM
      without significant reduction in conversion.

PMID- 20689952
TI  - Sulforaphane potentiates oxaliplatin-induced cell growth inhibition in colorectal
      cancer cells via induction of different modes of cell death.
AB  - The objective of this study was to investigate, whether the plant-derived
      isothiocyanate Sulforaphane (SFN) enhances the antitumor activities of the
      chemotherapeutic agent oxaliplatin (Ox) in a cell culture model of colorectal
      cancer. Caco-2 cells were cultured under standard conditions and treated with
      increasing concentrations of SFN [1-20 MUM] and/or Ox [100 nM-10 MUM]. For co
      incubation, cells were pre-treated with SFN for 24 h. Cell growth was determined
      by BrdU incorporation. Drug interactions were assessed using the combination
      index method (CI) (Cl < 1 indicates synergism). Apoptotic events were
      characterized by different ELISA techniques. Protein levels were examined by
      Western blot analysis. Annexin V- and propidium iodide (PI) staining followed by
      FACS analysis was used to differentiate between apoptotic and necrotic events.
      SFN and Ox alone inhibited cell growth of Caco-2 cells in a dose-dependent
      manner, an effect, which could be synergistically enhanced, when cells were
      incubated with the combination of both agents. Co-treated cells further displayed
      distinctive morphological changes that occurred during the apoptotic process,
      such as cell surface exposure of phosphatidylserine, membrane blebbing as well as
      the occurence of cytoplasmic histone-associated DNA fragments. Further
      observations thereby pointed toward simultaneous activation of both extrinsic and
      intrinsic apoptotic pathways. With increasing concentrations and treatment
      duration, a shift from apoptotic to necrotic cell death could be observed. In
      conclusion, the data suggest that the isothiocyanate SFN sensitizes colon cancer
      cells to Ox-induced cell growth inhibition via induction of different modes of
      cell death.

PMID- 20689953
TI  - Genetic and functional diversity among the antagonistic potential fluorescent
      pseudomonads isolated from tea rhizosphere.
AB  - Twenty-five fluorescent pseudomonads from rhizospheric soil of six tea gardens in
      four district of Upper Assam, India were isolated and screened for antagonistic
      activity against fungal pathogens such as Fusarium oxysporum f. sp. raphani
      (For), Fusarium oxysporum f. sp. ciceri (Foc), Fusarium semitectum (Fs), and
      Rhizoctonia solani (Rs); and bacterial pathogens-Staphylococcus aureus (Sa),
      Escherichia coli (Ec), and Klebsiella pneumoniae (Kp). Most of the isolates
      exhibited strong antagonistic activity against the fungal pathogens and gram
      positive bacterium i.e. Staphylococcus aureus. Productions of siderophore,
      salicylic acid (SA), hydrogen cyanide (HCN), and cell wall-degrading enzyme
      (chitinase) were studied to observe the possible mechanisms of antagonistic
      activity of the isolates. Correlation between the antagonistic potentiality of
      some isolates and their levels of production of siderophore, salicylic acid, and
      hydrogen cyanide was observed. Out of the 25 isolates, antibiotic-coding genes,
      2,4-diacetylphloroglucinol (DAPG) and pyoluteorin (PLT) were detected in the
      isolates, Pf12 and Pf373, respectively. Genetic diversity of these fluorescent
      pseudomonads were analyzed with reference to four strains of Pseudomonas
      fluorescens NICM 2099(T), P. aeruginosa MTCC 2582(T), P. aureofaciens NICM
      2026(T), and P. syringae MTCC 673(T). 16S rDNA-RFLP analysis of these isolates
      using three tetra cutter restriction enzymes (HaeIII, AluI and MspI) revealed two
      distinct clusters. Cluster A comprised only two isolates Pf141 and 24-PfM3, and
      cluster B comprised 23 isolates along with four reference strains.

PMID- 20689955
TI  - Retrospective analysis of the effectiveness of first-line antiepileptic drugs for
      generalized onset and unclassified epileptic seizures in Chinese children.
AB  - BACKGROUND AND PURPOSE: Based on the time until treatment failure, we
      retrospectively analyzed 389 children to compare the long-term effectiveness of
      first-line antiepileptic drugs (AEDs) in children with generalized onset or
      unclassified epileptic seizures. METHODS: Analyses were based on time until
      treatment failure and time until remission. RESULTS: In terms of time until
      treatment failure, the failure rates of topiramate and carbamazepine were higher
      than that of sodium valproate (p < 0.05). For time until 1-year remission, sodium
      valproate was found to be significantly better than either topiramate or
      carbamazepine (p < 0.05). For the subgroup with generalized onset epilepsy,
      sodium valproate was much better than either topiramate or carbamazepine (p <
      0.05). No significant differences were found between topiramate and carbamazepine
      (p = 0.319). For unclassified epileptic seizures, no significant differences were
      found among the three AEDs. CONCLUSION: Sodium valproate should be the drug of
      choice for patients with children with generalized onset, and no significant
      differences were found among the three AEDs in unclassified epileptic seizures.

PMID- 20689957
TI  - The effect of bevacizumab on colon anastomotic healing in rats.
AB  - PURPOSE: The aim of the study was to investigate the effect of angiogenesis
      inhibition by bevacizumab, a monoclonal anti-vascular endothelial growth factor
      (VEGF) antibody, on the healing process of colonic anastomoses in rats, assessing
      some specific involved factors. This new agent is used mainly in metastatic
      colorectal cancer. The angiogenesis plays an important role in both wound healing
      and metastatic invasion and spread of malignant cells. There has not been any
      evidence assessing the optimal time for its safe use in operated patients.
      MATERIALS AND METHODS: Forty Wistar rats were randomly allocated into four equal
      groups. A colonic anastomosis was performed in all rats. Half of them received
      intraoperatively a single dose of bevacizumab 5 mg/body weight and the rest
      received placebo. The animals were sacrificed on the 7th (Avastin 7th, placebo
      7th) and 14th (Avastin 14th, placebo 14th) postoperative day. The anastomosis was
      resected and sent for histological study and for tissue biochemical assays (VEGF,
      endothelin-1 (ET-1), C-reactive protein (CRP), pro-oxidant-antioxidant balance
      (PAB), carbonylated proteins, hydroxyproline) using specific enzyme-linked
      immunosorbent assay kits. For statistical analysis, the Mann-Whitney U test was
      used (of statistical significance when P < 0.05). RESULTS: No complication or
      anastomotic dehiscence was observed. Histology did not reveal statistically
      significant differences between groups concerning degree of inflammation,
      fibroblasts, collagen, and fibrosis. Likewise, hydroxyproline levels did not
      differ. However, some statistically significant differences were found in VEGF,
      CRP and carbonyl proteins (Avastin 7th vs placebo 7th, placebo 14th vs placebo
      7th), ET-1, and PAB (Avastin 14th vs Avastin 7th), which did not finally affect
      the collagen synthesis marker hydroxyproline, nor did the anastomotic strength.
      CONCLUSIONS: Bevacizumab, when administered intraoperatively, has no significant
      effect on colon anastomotic healing in rats despite a transient mild ischemia.

PMID- 20689958
TI  - Treatment of the anastomotic complications in patients with Crohn's disease.
AB  - PURPOSE: Postoperative anastomotic complications in patients with Crohn's disease
      undergoing bowel resections have a detrimental influence on the long-term
      outcome. The aim of this study was to evaluate whether patients' prognosis is
      affected by various treatment strategies of anastomotic complications. METHODS:
      The term anastomosis-related "intraabdominal septic complication" (IASC) was used
      for anastomotic leaks, intraabdominal abscesses, anastomotic fistula,
      peritonitis. Only patients with these complications have been included in the
      study. Outcome parameters were "surgical recurrence" (i.e., need for repeat bowel
      resections) and "good surgical outcome" (i.e., no death, no surgical recurrence,
      no stoma, no enterocutaneous fistula). Patients in group 1 were treated by taking
      the affected anastomosis down and creating an end stoma. The anastomosis has been
      preserved in patients of group 2. RESULTS: Between 1992 and Aug 2009, IASC
      occurred after 56 ileocolic resections for ileal disease and after 26 resections
      for Crohn's colitis. In patients with ileal disease, 5-year surgical recurrence
      rate was lower (0% vs. 65%, p = 0.0020) and a good surgical outcome was achieved
      more frequently at 2 years (100% vs. 25%, p = 0.0001) in group 1 than in group 2.
      There was no significant difference of long-term outcome between groups in
      patients with Crohn's colitis. CONCLUSION: In patients suffering anastomotic
      complications after ileocolic resection for ileal Crohn's disease, the prognosis
      can be significantly improved by taking down the anastomosis and creating an end
      ileostomy. Anastomosis can be preserved without an outcome impairment in many
      patients with Crohn's colitis.

PMID- 20689959
TI  - Comparative analysis of endometrial blood flow on the day of hCG by 2D Doppler in
      two groups of women with or without genital tuberculosis undergoing IVF-ET in a
      developing country.
AB  - OBJECTIVE: To evaluate the endometrial blood flow by two-dimensional power
      Doppler ultrasound as possible implantation markers and pregnancy predictors in
      women with and without genital tuberculosis undergoing in vitro fertilization
      embryo transfer cycle (IVF-ET). METHODS: This was a prospective observational
      study. A total of 183 infertile women were recruited from our IVF-ET program from
      January to December 2009. Women with tubal factor, male factor and unexplained
      infertility were included in the study. RESULTS: The age, duration of infertility
      and BMI of the women were comparable in both the groups. The mean gonadotropin
      usage in Group 1 was 2,881.3 IU (+/-SD 949.7) and 3,077.8 (+/-SD 927.9) in Group
      2. Total number of eggs obtained, duration (days) of stimulation, Estradiol (E2)
      concentration and endometrial thickness (in mm) showed no significant difference
      in the two groups. Even the peak systolic velocity, pulsatility index (PI) and
      resistance index (RI) was not statistically significant between the two groups.
      Pregnancy and implantation was higher in women with endometrial flow in zone 3 in
      both the groups though it did not reach any statistical significance. CONCLUSION:
      The present study showed no difference in endometrial blood flow and pregnancy
      rates in patients with or without genital tuberculosis.

PMID- 20689960
TI  - Vulvar reconstruction using a "V-Y" fascio-cutaneous gluteal flap: a valid
      reconstructive alternative in post-oncological loss of substance.
AB  - OBJECTIVE: We will present our experience in vulvar reconstruction using a local
      fascio-cutaneous flap, in order to get an easier intra-operative management and a
      good post-operative outcome. METHODS: Between May 2006 and December 2008, eight
      patients with vulvar carcinomas underwent a vulvar reconstruction, using a V-Y
      advancement flap of the gluteal fold. This fascio-cutaneous flap, based on the
      perforator vessels originated from the internal pudendal artery, was used for the
      reconstructive treatment of patients who had undergone a vulvectomy with medium
      size defects. RESULTS: All the 16 flaps prepared survived without major
      complications. Walking and sitting positions were restored in few post-operative
      days. Length of hospitalisation was 2-3 weeks. The flaps restored sensitivity few
      months after surgery. In no case the surgical scars needed being revised.
      CONCLUSIONS: The follow-up results proved satisfactory in terms of patients'
      compliance and morphological results. The flap appeared to be thin, well
      vascularised and very flexible in its advancement. The post-operative follow-up
      is characterised by a rapid healing and a low incidence of short- and long-term
      complications.

PMID- 20689961
TI  - Advances in multiple sclerosis research in 2009.
AB  - The following review summarizes the progress in multiple sclerosis research
      published in the Journal of Neurology in 2009.

PMID- 20689962
TI  - Outcome and consequences according to the type of transient loss of
      consciousness: 1-year follow-up study among primary health care patients.
AB  - The prognosis of transient loss of consciousness (LOC) was studied in a one-year
      follow-up survey. Included were adult patients referred by primary health care
      physicians for a non-acute specialist consultation during the 2-year period from
      01.10.1999 to 30.9.2001. The main outcome measures were recurrence of LOCs during
      the follow-up, fear of recurrence, injuries, and employment. Altogether, 109
      consecutive patients were followed and 39 (36%) suffered a recurrence during the
      one-year follow-up: 17 (30%) with syncope, 16 (43%) with seizure and six (38%)
      with uncertain type of LOC. The first ever seizure recurred in 5/9 (56%) during
      the first year, but only 1 of 17 (6%) first syncope attacks. There was no
      difference in the recurrence rate if the patient had had previous attacks prior
      to the index LOC. Injuries, mainly minor, were associated with LOCs in 56% of
      patients. The risk of injury was highest (83%) with alcohol-related seizures. The
      unemployment rate was especially high in the seizure group. Fear of recurrence
      was more common at the beginning than at the end of the follow-up. CONCLUSIONS:
      Seizures recur relatively often, but also recurrent syncope needs more attention-
      both may cause fear and lead to injuries.

PMID- 20689963
TI  - Photodynamic therapy for polypoidal choroidal vasculopathy.

PMID- 20689964
TI  - Intravitreal bevacizumab injection for persistent serous retinal detachment
      associated with Vogt-Koyanagi-Harada disease.
AB  - BACKGROUND: To introduce a case of Vogt-Koyanagi-Harada (VKH) disease in which
      the serous retinal detachment (SRD), refractory to the systemic steroid therapy,
      was resolved in a short time after an intravitreal injection of bevacizumab.
      METHODS: Interventional case report to show the effect of bevacizumab for the SRD
      in a VKH patient. RESULTS: A 42-year-old woman, diagnosed with VKH disease,
      showed decreased visual acuities and multiple SRDs in both eyes. The best
      corrected visual acuity (BCVA) was FC 30 cm in both eyes. On optical coherence
      tomography (OCT), multiple SRDs were confirmed. On OCT, the height of SRD in the
      central fovea area was 1119 MUm in the right eye and 1151 MUm in the left eye.
      After high-dose steroid treatment for 5 weeks, the SRD in the left eye was
      completely resolved, however, the SRD in the right eye was persisted. At the
      time, the height of SRD in the right eye was 884 MUm and the BCVA was 0.1. For
      the treatment of persistent SRD causing a decreased visual acuity despite a long
      term high-dose course of systemic steroid therapy, an intravitreal injection of
      1.25 mg bevacizumab was performed for the right eye, following an informed
      consent. One week later, there was fast and complete reabsorption of multiple
      SRDs in the right eye. The retinal thickness in the foveal area was measured to
      be 189 MUm by OCT and the BCVA was improved to 0.7. DISCUSSION: An intravitreal
      injection of bevacizumab combined with systemic steroid in VKH is expected to
      shorten the time for the persistent presence of SRD and to prevent the permanent
      visual impairment.

PMID- 20689965
TI  - The effect of vitamin C on upper respiratory infections in adolescent swimmers: a
      randomized trial.
AB  - The risk of upper respiratory infections (URIs) is increased in people who are
      under heavy physical stress, including recreational and competitive swimmers.
      Additional treatment options are needed, especially in the younger age group. The
      aim of this study was to determine whether 1 g/day vitamin C supplementation
      affects the rate, length, or severity of URIs in adolescent swimmers. We carried
      out a randomized, double-blind, placebo-controlled trial during three winter
      months, among 39 competitive young swimmers (mean age 13.8 +/- 1.6 years) in
      Jerusalem, Israel. Vitamin C had no effect on the incidence of URIs (rate ratio =
      1.01; 95% confidence interval (CI) = 0.70-1.46). The duration of respiratory
      infections was 22% shorter in vitamin C group, but the difference was not
      statistically significant. However, we found a significant interaction between
      vitamin C effect and sex, so that vitamin C shortened the duration of infections
      in male swimmers by 47% (95% CI: -80% to -14%), but had no effect on female
      swimmers (difference in duration: +17%; 95% CI: -38% to +71%). The effect of
      vitamin C on the severity of URIs was also different between male and female
      swimmers, so that vitamin C was beneficial for males, but not for females. Our
      study indicates that vitamin C does not affect the rate of respiratory infections
      in competitive swimmers. Nevertheless, we found that vitamin C decreased the
      duration and severity of respiratory infections in male swimmers, but not in
      females. This finding warrants further research.

PMID- 20689966
TI  - Kennel dogs as sentinels of Leishmania infantum, Toxoplasma gondii, and Neospora
      caninum in Majorca Island, Spain.
AB  - Kennel dogs can serve as sentinels and/or reservoirs of diseases of veterinary
      and zoonotic interest because they have often roamed free and lived outdoors,
      thus being exposed to pathogens. We tested dogs from the kennel of Inca
      (Majorca/Mallorca, Balearic Islands, Spain) for evidence of infection with three
      protozoan parasites: Leishmania infantum, Toxoplasma gondii, and Neospora
      caninum. Exposure to L. infantum was found in 56.3% of 48 dogs (37.5% by Western
      blot, 43.8% by PCR). Only 30% of infected dogs had leishmaniasis-like lesions.
      Seroprevalence to T. gondii was 58.7% of 46 dogs using the modified agglutination
      test (MAT, titer 1:25). None of the 44 dogs tested had N. caninum antibodies
      using a commercial competitive ELISA, probably because the surveyed dogs did not
      roam in the proximity of cattle farms. Results confirm the endemicity of L.
      infantum and also the widespread presence of T. gondii in the Mediterranean
      island of Majorca.

PMID- 20689967
TI  - Anthelmintic activity of steroidal saponins from Dioscorea zingiberensis C. H.
      Wright against Dactylogyrus intermedius (Monogenea) in goldfish (Carassius
      auratus).
AB  - Dactylogyrus intermedius is one of the most pathogenic monogenean parasites on
      the gills of captive fish and can cause serious problem in aquaculture. To
      attempt controlling this parasite and explore novel potential antiparasitic
      agents, the present study was designed to investigate the anthelmintic activity
      of Dioscorea zingiberensis C. H. Wright against D. intermedius in goldfish under
      in vivo conditions. Bioactivity-guided fractionation and isolation of the
      compounds responsible for anthelmintic activity was carried out with the
      ethanolic extract yielding two bioactive compounds. Using MS, (1)H NMR, (13)C NMR
      spectroscopic analyses, the two compounds were identified as trillin and
      gracillin. The results of in vivo anthelmintic efficacy assay showed that the 48
      h median effective concentrations (EC(50)) are 26.48 mg L(-1) for trillin and
      0.18 mg L(-1) for gracillin. The 48-h acute toxicity tests (LD(50)) of trillin
      and gracillin were found to be 73.11 and 1.40 mg L(-1) for goldfish,
      respectively. The resulting therapeutic indices for the two active compounds are
      2.76 and 7.78, respectively. These data confirmed that both trillin and gracillin
      are effective against D. intermedius, and the gracillin exhibits more interesting
      perspectives for the development of a candidate antiparasitic agent.

PMID- 20689968
TI  - Insecticidal and larvicidal activities of medicinal plant extracts against
      mosquitoes.
AB  - In recent years, use of environment friendly and biodegradable natural
      insecticides of plant origin have received renewed attention as agents for vector
      control because they are rich in bioactive chemicals, active against a limited
      number of species including specific target insects, and biodegradable. The
      present study was carried out to evaluate the adulticidal, repellent, and
      larvicidal activity of crude hexane, ethyl acetate, and methanol extracts of
      eight plants, viz. Aristolochia indica L., Cassia angustifolia Vahl, Diospyros
      melanoxylon Roxb., Dolichos biflorus L., Gymnema sylvestre (Retz) Schult,
      Justicia procumbens L., Mimosa pudica L., and Zingiber zerumbet L., were tested
      against adult and early fourth instar larvae of Culex gelidus Theobald and Culex
      quinquefasciatus Say (Diptera: Culicidae). The effective adult mortality was
      observed in methanol extract of A. indica, ethyl acetate extract of D. biflorus,
      and ethyl acetate and hexane extract of Z. zerumbet against C. gelidus and C.
      quinquefasciatus (LD(50) =37.75, 78.56, 129.44, 86.13, 80.06, 112.42, 53.83, and
      46.61; LD(90) =166.83, 379.14, 521.50, 289.83, 328.18, 455.72, 181.15, and 354.50
      ppm, respectively). Complete protections for 150 min were found in hexane and
      methanol extract of A. indica and Z. zerumbet at 1,000 ppm against mosquito
      bites. The highest larval mortality was found in the hexane extract of Z.
      zerumbet, ethyl acetate extract of D. biflorus, and methanol extracts of A.
      indica against C. gelidus (LC(50) =26.48, 33.02, and 12.47 ppm; LC(90) =127.73,
      128.79, and 62.33 ppm) and against C. quinquefasciatus (LC(50) =69.18, 34.76, and
      25.60 ppm; LC(90) =324.40, 172.78, and 105.52 ppm), respectively, after 24 h. The
      plant extracts are potential to be used as an ideal eco-friendly approach for the
      control of the Japanese encephalitis vector, C. gelidus, and lymphatic filariasis
      vector, C. quinquefasciatus.

PMID- 20689969
TI  - Effect of Chrysosporium keratinophilum metabolites against Culex quinquefasciatus
      after chromatographic purification.
AB  - Chrysosporium keratinophilum is known to be a keratinophilic fungus and an
      effective mosquito control agent. This fungus was grown on Sabauraud dextrose
      broth in the laboratory at 25 degrees C, while the relative humidity was
      maintained at 75 +/- 5% for 15 days. Filtration process of metabolites was done
      using whatman-1 filter paper, column chromatography and flash, chromatography.
      Larvicidal efficacy was performed against all instars of Culex quinquefasciatus.
      Larvicidal efficacy was performed at six different concentrations with different
      effective ratios (ethanol/metabolites: 9:1, 8:2, 7:3, 6:4, 5:5, 4:6, 3:7, 2:8,
      and 1:9). The mortality values were then subjected by the probit analysis. The
      larval mortalities were observed for a period of 24, 48, and 72 h, respectively.
      The first and second instars were highly susceptible to 2:8 ratio. In the first
      instar after column chromatography, LC(50) =26.66 ppm, LC(90) =121.96 ppm, LC(99)
      =231.86 ppm were observed after 72 h, while after flash chromatography the LC(50)
      =20 ppm, LC(90) =123.02 ppm, LC(99) =281.83 ppm were observed after 48 h. In the
      second instar after column chromatography, LC(50) =18.19 ppm, LC(90) =102.32 ppm,
      LC(99) =162.18 ppm were observed after 72 h, while doing flash chromatography
      100% mortality could be recorded after 24 h. In the third instar after column
      chromatography, the LC(50) =38.01 ppm, LC(90) =131.82 ppm, LC(99) =245.47 ppm
      were observed after 72 h, while after flash chromatography the LC(50) =17.78 ppm,
      LC(90) =100 ppm, LC(99) =151.35 ppm. In the fourth instar, LC(50) =61.65 ppm,
      LC(90) =181.97 ppm, LC(99) =436.51 ppm, while after flash chromatography LC(50)
      =40 ppm, LC(90) =120 ppm, and LC(99) =223.87 ppm were observed after 72 h. The
      extracellular metabolites of C. keratinophilum could be a fungal based larvicides
      resource for the control of C. quinquefasciatus larvae. This could be another
      agent for biotechnological exploitation, if found suitable in field trials.

PMID- 20689970
TI  - In-advance trans-medullary stimulation of bone marrow enhances spontaneous repair
      of full-thickness articular cartilage defects in rabbits.
AB  - Mesenchymal stromal cells (MSCs), especially those lying close to cartilage
      defects, are an important cell source for cartilage regeneration. We hypothesize
      that a larger number of MSCs might become available, if the bone marrow in the
      immediate vicinity of the subchondral bone is stimulated for MSCs in advance of
      the creation of cartilage defects. A trans-medullary passage-way reaching the
      immediate vicinity of the subchondral bone was created 4 days prior to the
      creation of cartilage defects. In another setting, basic fibroblast growth factor
      (bFGF) was administered through the trans-medullary passage-way in order to
      augment the stimulation of MSCs. The rabbits were killed at various times after
      the creation of cartilage defects. Triple staining of bromodeoxyuridine (BrdU),
      CD44 and CD45 and histological evaluation were subsequently performed. A
      considerable proportion of the proliferating cells were identified as bone-marrow
      derived MSCs. Enumeration of BrdU-positive cells demonstrated that trans
      medullary stimulation, especially with bFGF, increased the number of
      proliferating cells. The histological grading score of trans-medullary
      stimulation with bFGF group was superior to that of the other groups. Thus, in
      advance stimulation of the bone marrow effectively increases the number of
      proliferating cells. The putative progenitor cells for chondrocytes stimulated
      thereby are likely to be recruited to the osteochondral defects at the
      appropriate time, contributing to the repair of full-thickness articular
      cartilage defects at the early follow-up time point.

PMID- 20689971
TI  - Posterior listhesis of a lumbar vertebra in spinal tuberculosis.
AB  - The management of spinal tuberculosis, especially in children, is controversial.
      In children, vertebral destruction is more severe than adults because of the
      cartilaginous nature of their bone. Modern chemotherapy has significantly
      decreased mortality in spinal tuberculosis, but morbidity remains high. Without
      early surgery, patients can develop severe kyphosis leading to respiratory
      insufficiency, painful costopelvic impingement and paraplegia. Lumbar kyphosis
      results in early degenerative lumbar canal stenosis and is cosmetically
      unacceptable. We report a paediatric case of atypical spinal tuberculosis
      demonstrating the need for early surgical intervention to prevent significant
      spinal instability and neurologic deficit. A 12-year-old girl presented with
      increasing ambulatory difficulty and double incontinence 4 months after
      initiating treatment for pulmonary tuberculosis. There was no history of
      traumatic injury. Examination revealed severe lower limb neurologic deficit, with
      hypotonia, areflexia, marked sensory loss, and grade 0/5 power in both lower
      limbs. Plain radiographs and magnetic resonance imaging (MRI) demonstrated grade
      IV posterior listhesis of the L2 vertebral body over L3, cauda equina compression
      and bilateral psoas abscesses. Erosion of both the body and pedicle of L2 was
      observed. Both serology and pus drained from the psoas abscesses were negative
      for microorganisms. The patient underwent an L2 vertebrectomy via a left
      retroperitoneal approach. A titanium cage packed with autologous bone graft was
      inserted, and the spine was stabilized by fixation with screw and rods.
      Histopathology confirmed a diagnosis of tuberculosis. Eighteen months following
      the procedure, the patient has regained some power in her right leg and has
      completed her course of anti-tuberculous chemotherapy, but remains wheelchair
      bound. To our knowledge, this is the first reported case of posterior listhesis
      secondary to spinal tuberculosis. Here, we discuss the possible management
      options in such a case, and the indications for surgery. As the global HIV/AIDS
      epidemic causes a resurgence in tuberculosis, increased awareness among the
      medical community regarding the atypical presentations of spinal tuberculosis is
      necessitated; both in the developing world where advanced clinical presentations
      are common, and in the developed world where spinal tuberculosis is an often
      neglected diagnosis.

PMID- 20689972
TI  - The effect of human immunodeficiency virus type 1 (HIV-1) gp41 variability on
      antibody detection.
AB  - To determine whether genetic variability influences the ability to detect
      antibody, nine gp41 ectodomain recombinant proteins from human immunodeficiency
      virus type 1 (HIV-1) CRF07_BC, CRF01_AE and subtype B' were expressed in a
      bacterial expression system and purified. An indirect sandwich ELISA was
      developed with individual purified recombinant proteins. Plasma samples from 26
      individuals infected with HIV-1 of different subtypes and four samples from the
      1st international antibody reference panel were tested against each recombinant
      protein by ELISA. Heat-map and two-dimensional hierarchical clustering methods
      revealed that ELISA reactivity against antigens derived from the same subtypes
      clustered together. This suggests a similar reactivity pattern among infections
      of the same subtype, and thus the antigenicity of gp41 recombinant proteins may
      vary depending on the subtype, and subtype-related serotypes may exist among
      these antigens. Using association analysis methods, eight signature sites related
      to the subtype-specific reactivity patterns were identified. This study provides
      valuable information for the development of diagnostic assays with the ability to
      detect broadly cross-reactive antibodies induced by infection with different HIV
      1 subtypes.

PMID- 20689973
TI  - Female germ unit in Genlisea and Utricularia, with remarks about the evolution of
      the extra-ovular female gametophyte in members of Lentibulariaceae.
AB  - Lentibulariaceae is the largest family among carnivorous plants which displays
      not only an unusual morphology and anatomy but also the special evolution of its
      embryological characteristics. It has previously been reported by authors that
      Utricularia species lack a filiform apparatus in the synergids. The main purposes
      of this study were to determine whether a filiform apparatus occurs in the
      synergids of Utricularia and its sister genus Genlisea, and to compare the female
      germ unit in these genera. The present studies clearly show that synergids in
      both genera possess a filiform apparatus; however, it seems that Utricularia
      quelchii synergids have a simpler structure compared to Genlisea aurea and other
      typical angiosperms. The synergids are located at the terminal position in the
      embryo sacs of Pinguicula, Genlisea and were probably also located in that
      position in common Utricularia ancestor. This ancestral characteristic still
      occurs in some species from the Bivalvaria subgenus. An embryo sac, which grows
      out beyond the limit of the integument and has contact with nutritive tissue,
      appeared independently in different Utricularia lineages and as a consequence of
      this, the egg apparatus changes position from apical to lateral.

PMID- 20689974
TI  - Inhibition of a bacterial O-GlcNAcase homologue by lactone and lactam
      derivatives: structural, kinetic and thermodynamic analyses.
AB  - The dynamic, intracellular, O-GlcNAc modification is of continuing interest and
      one whose study through targeted "chemical genetics" approaches is set to
      increase. Of particular importance is the inhibition of the O-GlcNAc hydrolase, O
      GlcNAcase (OGA), since this provides a route to elevate cellular O-GlcNAc levels,
      and subsequent phenotypic evaluation. Such a small molecule approach complements
      other methods and potentially avoids changes in protein-protein interactions that
      manifest themselves in molecular biological approaches to O-GlcNAc transferase
      knockout or over-expression. Here we describe the kinetic, thermodynamic and
      three-dimensional structural analysis of a bacterial OGA analogue from
      Bacteroides thetaiotaomicron, BtGH84, in complex with a lactone oxime (LOGNAc)
      and a lactam form of N-acetylglucosamine and compare their binding signatures
      with that of the more potent inhibitor O-(2-acetamido-2-deoxy-D
      glucopyranosylidene)amino N-phenyl carbamate (PUGNAc). We show that both LOGNAc
      and the N-acetyl gluconolactam are significantly poorer inhibitors than PUGNAc,
      which may reflect poorer mimicry of transition state geometry and steric clashes
      with the enzyme upon binding; drawbacks that the phenyl carbamate adornment of
      PUGNAc helps mitigate. Implications for the design of future generations of
      inhibitors are discussed.

PMID- 20689975
TI  - Airplane headache: a further case report of a young man.
AB  - Headache with normal examinations and imaging, occurring during an airplane
      flight has been rarely reported. We present a young patient with a new type of
      headache that appeared during flights: take-off and landing of a plane and was
      not associated with other conditions. This airplane headache is rather rare in
      population and the pathophysiology of this type is not clear. Secondary causes
      must be ruled out before the diagnosis of a primary headache is made.

PMID- 20689977
TI  - Cost-effectiveness of cognitive-behavioral group therapy for dysfunctional fear
      of progression in cancer patients.
AB  - Anxiety and fear are often associated with chronic conditions such as cancer.
      This paper targets the cost-effectiveness analysis of a cognitive-behavioral
      group therapy (CBT) in comparison to a client-centered, supportive-experiential
      group therapy (SET) in cancer patients with dysfunctional fear of progression. An
      incremental cost-effectiveness analysis was performed using data from a
      randomized controlled trial among cancer patients receiving inpatient
      rehabilitation. The means, 95% confidence intervals [95% CI], incremental cost
      effectiveness graphic and acceptability curve were obtained from 1,000 bootstrap
      replications. A total of 174 patients were included in the economic evaluation.
      The estimated means [95% CI] of direct costs and reduction of fear of progression
      were <euro>9,045.03 [6,359.07; 12,091.87] and 1.41 [0.93; 1.92] for patients in
      the SET and <euro>6,682.78 [4,998.09; 8,440.95] and 1.44 [1.02; 1.09] for
      patients in the CBT. The incremental cost-effectiveness ratio [95% CI] amounts to
      minus <euro>78,741.66 [-154,987.20; 110,486.32] for an additional unit of effect.
      Given the acceptability curve, there is a 92.4% chance that the CBT, compared
      with the SET, is cost-effective without the need of additional costs to payers.
      Our main result is the superior cost-effectiveness of the cognitive-behavioral
      intervention program in comparison to the non-directive encounter group for our
      sample of cancer patients with high levels of anxiety.

PMID- 20689978
TI  - The apoptosis-inducing activity towards leukemia and lymphoma cells in a
      cyanobacterial culture collection is not associated with mouse bioassay toxicity.
AB  - Cyanobacteria (83 strains and seven natural populations) were screened for
      content of apoptosis (cell death)-inducing activity towards neoplastic cells of
      the immune (jurkat acute T-cell lymphoma) and hematopoetic (acute myelogenic
      leukemia) lineage. Apoptogenic activity was frequent, even in strains cultured
      for decades, and was unrelated to whether the cyanobacteria had been collected
      from polar, temperate, or tropic environments. The activity was more abundant in
      the genera Anabaena and Microcystis compared to Nostoc, Phormidium, Planktothrix,
      and Pseudanabaena. Whereas the T-cell lymphoma apoptogens were frequent in
      organic extracts, the cell death-inducing activity towards leukemia cells resided
      mainly in aqueous extracts. The cyanobacteria were from a culture collection
      established for public health purposes to detect toxic cyanobacterial blooms, and
      54 of them were tested for toxicity by the mouse bioassay. We found no
      correlation between the apoptogenic activity in the cyanobacterial isolates with
      their content of microcystin, nor with their ability to elicit a positive
      standard mouse bioassay. Several strains produced more than one apoptogen,
      differing in biophysical or biological activity. In fact, two strains contained
      microcystin in addition to one apoptogen specific for the AML cells, and one
      apoptogen specific for the T-cell lymphoma. This study shows the potential of
      cyanobacterial culture collections as libraries for bioactive compounds, since
      strains kept in cultures for decades produced apoptogens unrelated to the mouse
      bioassay detectable bloom-associated toxins.

PMID- 20689979
TI  - T-Analyst: a program for efficient analysis of protein conformational changes by
      torsion angles.
AB  - T-Analyst is a user-friendly computer program for analyzing trajectories from
      molecular modeling. Instead of using Cartesian coordinates for protein
      conformational analysis, T-Analyst is based on internal bond-angle-torsion
      coordinates in which internal torsion angle movements, such as side-chain
      rotations, can be easily detected. The program computes entropy and automatically
      detects and corrects angle periodicity to produce accurate rotameric states of
      dihedrals. It also clusters multiple conformations and detects dihedral rotations
      that contribute hinge-like motions. Correlated motions between selected dihedrals
      can also be observed from the correlation map. T-Analyst focuses on showing
      changes in protein flexibility between different states and selecting
      representative protein conformations for molecular docking studies. The program
      is provided with instructions and full source code in Perl.

PMID- 20689980
TI  - The anticancer drug perillyl alcohol is a Na/K-ATPase inhibitor.
AB  - The monoterpene perillyl alcohol (POH) is a drug used in the treatment of several
      malignant tumors, including gliomas. The present study defines a POH inhibitory
      effect on Na/K-ATPase activity from kidney and brain guinea pig extracts and from
      a human glioblastoma cell line. This inhibition showed a high degree of
      selectivity toward the kidney enzyme expressing, as do glioblastoma cells, the
      alpha(1) subunit. Kinetic studies with purified enzymes showed a noncompetitive
      POH inhibition profile to Na(+) and K(+) and an uncompetitive inhibition towards
      ATP. Furthermore, potassium activated p-nitrophenylphosfatase activity of these
      purified preparations was not inhibited by POH, suggesting that this drug,
      differently from the classical inhibitor ouabain, acted in the initial phase of
      the enzyme's catalytic cycle. We suggest that POH antitumor action could be
      linked to its Na/K-ATPase binding properties.

PMID- 20689981
TI  - SMT-A07, a 3-(Indol-2-yl) indazole derivative, induces apoptosis of leukemia
      cells in vitro.
AB  - N-(2-(1H-indazol-3-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)-4-chloro-N-methylbenzamide
      (SMT-A07) is a novel 3-(Indol-2-yl) indazole derivative. The anticancer
      activities in vitro and the cell apoptosis-induction abilities of SMT-A07 on
      human leukemia HL60 and NB4 cell lines were investigated in this study. The
      results of MTT assay showed SMT-A07 was a potential and highly efficient
      antitumor compound with IC(50) values ranging from 0.09 to 1.19 MUM in five
      leukemia cell lines. SMT-A07 treatment for 24 h caused the increment of apoptosis
      rate from 6.88 to 49.72% in HL60 cells and from 8.72 to 56.28% in NB4 cells by
      flow cytometry analysis. Agarose gel electrophoresis showed DNA fragmentation
      that appeared after cells were exposed to SMT-A07. After SMT-A07 incubation, DAPI
      staining revealed the presence of DNA fragmentation, and perinuclear apoptotic
      body. SMT-A07 also resulted in a loss of DeltaPsim in both HL60 and NB4 cells by
      JC-1 staining. Moreover, apoptosis-related proteins were examined by western
      blotting to explore the mechanism of its cytotoxicity. SMT-A07 exposure caused
      down-regulation and cleavage of procaspase-8, procaspase-3, Bid, PARP and up
      regulation of cleaved caspase-8, cleaved caspase-3, PARP (Cleaved Fragment). In
      addition, the presence of pan-caspase inhibitor BOC-D-FMK prevented cells from
      caspase-3 activation, PARP cleavage, and subsequent apoptosis. Our study
      demonstrates that SMT-A07 displays an apparent antitumor activity with extensive
      anti-leukemia spectrum, and SMT-A07 can induce the apoptosis of HL60 and NB4
      cells activation of the caspase cascade, which deserves further development.

PMID- 20689982
TI  - The impact of psychiatric comorbidity on the return to work in patients
      undergoing herniated disc surgery.
AB  - INTRODUCTION: This study examines (1) return to work (RTW) and ability to work
      (ATW) rates, and the association with (2) psychiatric comorbidity and (3) socio
      demographic, illness-related, vocational and rehabilitation-related
      characteristics in herniated disc surgery patients. METHODS: In this longitudinal
      observational study 305 consecutive patients took part in face-to-face interviews
      during hospital stay. 277 patients also participated in a 3-month follow-up
      survey via telephone (drop-out rate 9%). Psychiatric comorbidity was assessed
      with the Composite International Diagnostic Interview (CIDI-DIA-X). Calculations
      were conducted via Chi-Square tests, independent T-tests and binary logistic
      regression analyses. RESULTS: 40.1% of the herniated disc patients in this study
      were able to RTW, 44.4% had regained their ATW 3 months after surgery.
      Psychiatric comorbidity appeared to be an important risk factor for RTW and ATW.
      Other risk factors were lower educational qualification, unemployment status, a
      lower subjective prognosis of gainful employment, a higher number of herniated
      discs in medical history, cervical disc surgery, and the existence of other
      chronic diseases, a longer hospital stay and higher pain intensity. Patients who
      did not RTW, or did not regain their ATW participated more often in inpatient
      rehabilitation. CONCLUSIONS: Identifying a high risk group for RTW and ATW at an
      early age is of utmost importance for the purpose of improving rehabilitation
      effects and to make a return to the work place easier. Specific interventions,
      such as social-medical counselling, pain therapy and management, as well as the
      assistance of mental health professionals during hospital and rehabilitation
      treatment are recommended for this risk group.

PMID- 20689983
TI  - Acculturation strategies and mental health in gay, lesbian, and bisexual youth.
AB  - In this article, we examine the impact of acculturation strategies on minority
      stress and mental health in lesbian, gay, or bisexual (LGB) youth in Flanders,
      Belgium. Building on previous identity minority studies and on the social stress
      model, we investigate how LGB youth acculturate within both the LGB subculture
      and mainstream society and how this correlates with their mental health. Our
      sample is taken from an online survey and represents 561 LGB youth aged 14
      through 21. The four traditional acculturation strategies are represented in this
      population (integration, separation, marginalization, assimilation). Bisexual
      boys are mostly absent from separation and integration strategies; gay and
      lesbian youth in middle adolescence are significantly more represented in the
      separation strategy compared to their late adolescence counterparts. Further, our
      findings suggest the relevance of identification with the LGB community,
      especially for internalized negative attitudes toward homosexuality. LGB youth
      who identify with the LGB community score significantly lower on this
      internalized homonegativity.

PMID- 20689984
TI  - Pentraxin 3 increase is much less pronounced than C-reactive protein increase
      after surgical procedures.
AB  - Pentraxin 3 is an acute phase marker that belongs to the same protein family as C
      reactive protein (CRP). The aim of this study was to compare the acute phase
      reactions of pentraxin 3 and CRP in humans. High sensitivity CRP and pentraxin 3
      were analyzed in blood samples from orthopedic surgery (n = 29) and coronary
      bypass patients (n = 21). The samples were collected prior to surgery and 4 and
      30 days after surgery, respectively. Both CRP and pentraxin 3 were significantly
      increased at day 4. Median pentraxin 3 values increased from 4,021 to 7,459 pg/mL
      in the orthopedic group and from 4,637 pg/mL to 10,419 pg/mL in the coronary
      bypass group while CRP increased from 6.3 mg/L to 151.6 mg/L and from 5.7 mg/L to
      176.3 mg/L in the same groups. Pentraxin 3 shows a much smaller increment in
      humans in comparison with CRP.

PMID- 20689985
TI  - Anti-inflammatory activity of n-propyl gallate through down-regulation of NF
      kappaB and JNK pathways.
AB  - The present study aimed to assess anti-inflammatory activity and underlying
      mechanism of n-propyl gallate, the n-propyl ester of gallic acid. n-Propyl
      gallate was shown to contain anti-inflammatory activity using two experimental
      animal models, acetic acid-induced permeability model in mice, and air pouch
      model in rats. It suppressed production of nitric oxide and induction of
      inducible nitric oxide synthase and cyclooxygenase-2 in the lipopolysaccharide
      (LPS)-stimulated RAW264.7 macrophage cells. It was able to diminish reactive
      oxygen species level elevated in the LPS-stimulated RAW264.7 macrophage cells. It
      also suppressed gelatinolytic activity of matrix metalloproteinase-9 enhanced in
      the LPS-stimulated RAW264.7 macrophage cells. It inhibited inhibitory kappaB
      alpha degradation and enhanced NF-kappaB promoter activity in the stimulated
      macrophage cells. It was able to suppress phosphorylation of c-Jun NH(2)-terminal
      kinase 1/2 (JNK1/2) and activation of c-Jun promoter activity in the stimulated
      macrophage cells. In brief, n-propyl gallate possesses anti-inflammatory activity
      via down-regulation of NF-kappaB and JNK pathways.

PMID- 20689986
TI  - Regeneration of the endothelium in vascular injury.
AB  - The endothelium mediates relaxations (dilatations) of the underlying vascular
      smooth muscle cells. The endothelium-dependent relaxations are due to the release
      of non-prostanoid vasodilator substances. The best characterized endothelium
      derived relaxing factor (EDRF) is nitric oxide (NO). The endothelial cells also
      release substances (endothelium-derived hyperpolarizing factor, EDHF) that cause
      hyperpolarization of the cell membrane of the underlying vascular smooth muscle.
      The release of EDRF from the endothelium can be mediated by both pertussis toxin
      sensitive G(i) (alpha(2)-adrenergic activation, serotonin, thrombin) and
      insensitive G(q) (adenosine diphosphate, bradykinin) coupling proteins. The
      ability of the endothelial cell to release relaxing factors can be upregulated by
      impregnation with estrogens, exercise and antioxidants, and down-regulated by
      oxidative stress and increased presence of oxidized LDL. Following injury or
      apoptotic death, the endothelium regenerates. However, in regenerated endothelial
      cells, there is an early selective loss of the pertussis-toxin sensitive
      mechanisms of EDRF-release. Functional studies suggest that abnormal handling of
      LDL because of increased oxidative stress play a key role in this selective loss.
      Genomic analysis demonstrates the emergence of fatty acid binding protein-A (A
      FBP) and metalloproteinase-7 (MMP7) in regenerated endothelial cells. The reduced
      release of NO resulting from the endothelial dysfunction in regenerated areas
      creates a locus minoris resistentiae which favors the occurrence of vasospasm and
      thrombosis as well as the initiation of atherosclerosis.

PMID- 20689987
TI  - Cardioprotection in the clinical setting-lessons from J-WIND studies.
AB  - INTRODUCTION: Both prevention and attenuation of ischemic heart disease are
      important issues, and there are three different strategies to save patients from
      the deleterious sequelae of ischemic injury. The first strategy is to remove the
      causes of ischemic heart disease; the second is to attenuate on-going ischemic
      and reperfusion injury; the third is to prevent the progression of cardiac
      remodeling and chronic heart failure following ischemic injury. EVIDENCE AND
      DISCUSSION: For prevention of acute myocardial infarction, it is widely accepted
      to treat high risk patients with aspirin and/or statins. On the other hand,
      several medications such as angiotensin converting enzyme inhibitors, aldosterone
      receptor antagonists and beta blockers have been used for the prevention of post
      infarction heart failure in patients who have suffered from an acute myocardial
      infarction. However, at present we do not have an adjunctive drug therapy to
      reduce infarct size in the acute phase in patients with myocardial infarction.
      Recently, the J-WIND trials suggested that an infusion of human atrial
      natriuretic peptide in the acute phase and oral administration of nicorandil in
      the chronic phase of infarction result in a better outcome in patients with a
      myocardial infarction. In this article we propose potential mechanisms for
      cardioprotection in patients with an acute myocardial infarction.

PMID- 20689988
TI  - Galectin-1 enhances astrocytic BDNF production and improves functional outcome in
      rats following ischemia.
AB  - Galectin-1, an endogenous mammalian lectin, has been implicated in a variety of
      CNS disorders. However, its role in cerebral ischemia is still elusive. In the
      present study, we investigated the effect of recombinant galectin-1 on production
      of astrocytic brain-derived neurotrophic factor (BDNF) and functional recovery
      following ischemia. Endogenous galectin-1 was found to be markedly upregulated,
      paralleled with increased astrocytic BDNF production under ischemic conditions
      both in vitro and in vivo. Administration of galectin-1 significantly enhanced
      the expression and secretion of astrocytic BDNF in dose dependent manner.
      Moreover, rats subjected to photochemical cerebral ischemia showed reduced
      neuronal apoptosis in ischemic boundary zone and improved functional recovery
      after brain infusion of galectin-1 (1 MUg/days, 7 days). These results suggest
      that induction of BDNF in astrocytes by galectin-1 may be a promising
      intervention to attenuate brain damage after stroke.

PMID- 20689989
TI  - The integration of a family systems approach for understanding youth obesity,
      physical activity, and dietary programs.
AB  - Rates of overweight in youth have reached epidemic proportions and are associated
      with adverse health outcomes. Family-based programs have been widely used to
      treat overweight in youth. However, few programs incorporate a theoretical
      framework for studying a family systems approach in relation to youth health
      behavior change. Therefore, this review provides a family systems theory
      framework for evaluating family-level variables in weight loss, physical
      activity, and dietary approaches in youth. Studies were reviewed and effect sizes
      were calculated for interventions that manipulated the family system, including
      components that targeted parenting styles, parenting skills, or family
      functioning, or which had novel approaches for including the family. Twenty-one
      weight loss interventions were identified, and 25 interventions related to
      physical activity and/or diet were identified. Overall, family-based treatment
      programs that incorporated training for authoritative parenting styles, parenting
      skills, or child management, and family functioning had positive effects on youth
      weight loss. Programs to improve physical activity and dietary behaviors that
      targeted the family system also demonstrated improvements in youth health
      behaviors; however, direct effects of parent-targeted programming is not clear.
      Both treatment and prevention programs would benefit from evaluating family
      functioning and parenting styles as possible mediators of intervention outcomes.
      Recommendations are provided to guide the development of future family-based
      obesity prevention and treatment programs for youth.

PMID- 20689991
TI  - Pulmonary hemorrhage in type 3 Gaucher disease: a case report.
AB  - A 2-year-old boy with type 3 Gaucher disease (GD) on treatment with enzyme
      replacement therapy (ERT) was found dead in bed having been apparently well the
      night before. At the time of diagnosis, he had significant respiratory symptoms
      (severe and persistent bouts of coughing) that had been attributed to Gaucher
      lung infiltration and that were controlled by inhaled and orally administered
      steroids. These symptoms had begun to reappear just prior to death. Postmortem
      revealed extensive pulmonary hemorrhage and intra-alveolar collections of Gaucher
      cells. There was very little evidence of GD elsewhere. Death was ascribed to
      pulmonary hemorrhage secondary to GD. The pathogenesis was unclear. To the best
      of our knowledge, this is the first case of isolated pulmonary hemorrhage
      secondary to GD and may represent a hitherto unrecognized complication of this
      condition. Given the apparent temporal relationship, we propose that it
      represented a severe, terminal event in the course of Gaucher lung disease. 

PMID- 20689992
TI  - Numerical studies of continuous nutrient delivery for tumour spheroid culture in
      a microchannel by electrokinetically-induced pressure-driven flow.
AB  - Continuous nutrient delivery to cells by pressure-driven flow is desirable for
      cell culture in lab-on-a-chip devices. An innovative method is proposed to
      generate an induced pressure-driven flow by using an electrokinetically-driven
      pump in a H-shape microchannel. A three-dimensional numerical model is developed
      to study the effectiveness of the proposed mechanism. It is shown that the
      average velocity of the generated pressure-driven flow is linearly dependent on
      the applied voltage. Considering the culture of a multicellular tumour spheroid
      (MTS) in such a microfluidic system, numerical simulations based on EMT6/Ro
      tumour cells is performed to find the effects of the nutrient distribution
      (oxygen and glucose), bulk velocity and channel size on the cell growth. Using an
      empirical formula, the growth of the tumour cell is studied. For low nutrient
      concentrations and low speed flows, it is found that the MTS grows faster in
      larger channels. It is also shown that, for low nutrient concentrations, a higher
      bulk liquid velocity provide better environment for MTS to grow. For lower
      velocities, it is found that the local MTS growth along the flow direction
      deviates from the average growth.

PMID- 20689994
TI  - Bone age and factors affecting skeletal maturation at diagnosis of paediatric
      Cushing's disease.
AB  - Paediatric Cushing's disease (CD) is usually associated with growth retardation,
      but there are only few published data on skeletal maturation at diagnosis. We
      analysed factors contributing to skeletal maturation and final height in Asian
      Indian patients with paediatric CD. We conducted retrospective analysis of 48
      patients (29 males; 19 females) with mean age: 14.84 years at diagnosis (range 9
      19 years). A single observer using the Greulich Pyle method determined the bone
      age (BA) of each child. BA delay, i.e. the difference between chronological age
      (CA) and BA, was compared with clinical and biochemical variables. BA delay was
      present in 35/48 (73%) patients (mean delay 1.6 years, range 0.5-5 years) and
      correlated negatively with height SDS (r = -0.594, P < 0.001) and positively with
      CA at diagnosis (r = 0.247, P < 0.05). There was no correlation with duration of
      symptoms before diagnosis, basal cortisol, midnight cortisol, ACTH or percentage
      suppression of low dose dexamethasone suppression cortisol (LDDST). We could not
      demonstrate any relationship between the duration of history before diagnosis and
      height SDS at final height. Mean final height SDS in patients was -1.84. We found
      that most children with CD had delayed BA and correlated significantly with CA
      and height SDS at diagnosis. Early diagnosis may reduce delay in skeletal
      maturation and thus contribute to optimal catch-up growth.

PMID- 20689996
TI  - [ProCor: an extramural screening on heart rate reduction in patients with chronic
      stable angina pectoris in Austria].
AB  - Based on the evidence from large clinical and epidemiological studies indicating
      an independent prognostic role of heart rate in cardiovascular disease, the
      assessment and correction of elevated heart rate is of significant prognostic
      relevance. In the present study conducted with the support of 74 specialists of
      Internal Medicine in 2009 in Austria, heart rate in patients with coronary heart
      disease (CHD) and chronic stable angina pectoris was evaluated in relation to pre
      existing and concomitant diseases, angina-severity (CCS), angina-symptoms and
      treatment. For all variables, descriptive statistical analyses were performed
      according to three predefined groups with heart rates <60 bpm (HR-1), 60-70 bpm
      (HR-2), and >70 bpm (HR-3). Of the 1280 patients 21.8% had a heart rate of <60
      bpm, 39.6% of 60-70 bpm, and 38.5% of >70 bpm. A significant association was
      shown between elevated heart rate and concomitant disease, e.g., peripheral
      artery disease (p = 0.046), psoriasis (p = 0.029), previous acute coronary
      syndrome (p = 0.001), COPD (p < 0.001), diabetes mellitus (p = 0.004), and
      depression (p < 0.001). CCS-severity was correlated with heart rates (mean
      values; CCS-0: 66.8 bpm, CCS-IV: 77.5 bpm). Angina-pectoris (AP) symptoms were
      more common in patients with heart rates of >70 bpm (HR-3: 1,2 AP-events/week; HR
      2: 1 AP-events/week; HR-1: 0,7 AP events/week; each time p < 0.001). The majority
      of patients were treated with betablockers (74%); yet, the average dose was
      approximately half the maximal recommended dose. Despite inadequate heart rate
      reduction in patients on betablockers, selective heart rate lowering agents such
      as ivabradine were used in only 1.6% of patients. Overall, these results
      illustrate that heart rate as an important therapeutic target in CHD-patients
      with chronic stable angina is still underestimated in contemporary clinical
      practice.

PMID- 20689997
TI  - Perspectives in drug development for metastatic renal cell cancer.
AB  - Patients with renal cell carcinoma (RCC) exhibit a spectrum of clinical outcomes,
      with some patients following an indolent clinical course and others displaying
      rapidly advancing disease. As evidence points to RCC being largely refractory to
      traditional chemotherapy and radiotherapy strategies, immunotherapeutic
      approaches played a dominant role in the management of metastatic RCC for a
      quarter of a century. Management of this challenging tumor has been
      revolutionized by the incorporation of molecularly targeted therapies such as
      inhibitors of pathways involving tyrosine kinase signaling and the mammalian
      target of rapamycin (mTOR). The improvements in disease stabilization and
      survival seen with these agents has meant that molecularly targeted therapy now
      forms the foundation for treating RCC and has resulted in a multitude of studies
      investigating similar compounds for efficacy in RCC. Despite this, the rationale
      for using immunomodulatory regimens remains strong and its ongoing place in this
      era of targeted treatments continues to pose interesting clinical questions. The
      challenge of maintaining durable responses from our current therapies persists
      and this review highlights the plethora of options now available in RCC treatment
      and the directions in which modern management are heading.

PMID- 20689998
TI  - Neuronal PINCH is regulated by TNF-alpha and is required for neurite extension.
AB  - During HIV infection of the CNS, neurons are damaged by viral proteins, such as
      Tat and gp120, or by inflammatory factors, such as TNF-alpha, that are released
      from infected and/or activated glial cells. Host responses to this damage may
      include the induction of survival or repair mechanisms. In this context, previous
      studies report robust expression of a protein called particularly interesting new
      cysteine histidine-rich protein (PINCH), in the neurons of HIV patients' brains,
      compared with nearly undetectable levels in HIV-negative individuals (Rearden et
      al., J Neurosci Res 86:2535-2542, 2008), suggesting PINCH's involvement in
      neuronal signaling during HIV infection of the brain. To address potential
      triggers for PINCH induction in HIV patients' brains, an in vitro system
      mimicking some aspects of HIV infection of the CNS was utilized. We investigated
      neuronal PINCH expression, subcellular distribution, and biological consequences
      of PINCH sequestration upon challenge with Tat, gp120, and TNF-alpha. Our results
      indicate that in neurons, TNF-alpha stimulation increases PINCH expression and
      changes its subcellular localization. Furthermore, PINCH mobility is required to
      maintain neurite extension upon challenge with TNF-alpha. PINCH may function as a
      neuron-specific host-mediated response to challenge by HIV-related factors in the
      CNS.

PMID- 20689999
TI  - CTPA as the gold standard for the diagnosis of pulmonary embolism.
AB  - PURPOSE: The estimated annual incidence of pulmonary embolism (PE) is between 69
      to 205 cases per 100,000 persons-years. New imaging studies have been developed
      during the past decade. Chest CTPA, especially multidetector CT, has proven to be
      superior or equal to PA angiography, even detecting smaller filling defects. We
      reviewed the differences in opinion to the diagnosis of PE between chest
      radiologists (CR) who interpret CTPA and interventional radiologists (IR) who
      perform PA angiography and what they consider the "gold standard" for the
      diagnosis of PE. METHODS: Two surveys were designed, one for chest radiologists
      and one for interventional radiologists. An e-mail survey was sent to the members
      of the Society of Thoracic Radiology and the Society of Interventional
      Radiologists. RESULTS: IR with < 10 years since finishing training were less
      likely to consider CTPA the gold standard, OR 0.45 (0.2-0.9). CR with < 10 years
      since finishing training were more likely to consider CTPA the gold standard, OR
      2.0 (1.1-3.9). Most IR performed < 5 PA angiographies in the last 2 years (69%).
      CR considered CTPA the gold standard for the diagnosis of PE, OR 3.3 (1.8-6.1).
      Binary logistic regression analysis for both groups demonstrated that the only
      variable associated with CTPA as gold standard for the diagnosis of PE was being
      a chest radiologist. CONCLUSION: The majority of the radiologists surveyed
      indicated that CTPA is the new reference standard for the diagnosis of pulmonary
      embolism. We agree with this statement based on the evidence available at this
      time.

PMID- 20690000
TI  - MIDG-Emerging grid technologies for multi-site preclinical molecular imaging
      research communities.
AB  - PURPOSE: Molecular imaging is the visualization and identification of specific
      molecules in anatomy for insight into metabolic pathways, tissue consistency, and
      tracing of solute transport mechanisms. This paper presents the Molecular Imaging
      Data Grid (MIDG) which utilizes emerging grid technologies in preclinical
      molecular imaging to facilitate data sharing and discovery between preclinical
      molecular imaging facilities and their collaborating investigator institutions to
      expedite translational sciences research. Grid-enabled archiving, management, and
      distribution of animal-model imaging datasets help preclinical investigators to
      monitor, access and share their imaging data remotely, and promote preclinical
      imaging facilities to share published imaging datasets as resources for new
      investigators. METHODS: The system architecture of the Molecular Imaging Data
      Grid is described in a four layer diagram. A data model for preclinical molecular
      imaging datasets is also presented based on imaging modalities currently used in
      a molecular imaging center. The MIDG system components and connectivity are
      presented. And finally, the workflow steps for grid-based archiving, management,
      and retrieval of preclincial molecular imaging data are described. RESULTS:
      Initial performance tests of the Molecular Imaging Data Grid system have been
      conducted at the USC IPILab using dedicated VMware servers. System connectivity,
      evaluated datasets, and preliminary results are presented. The results show the
      system's feasibility, limitations, direction of future research. CONCLUSIONS:
      Translational and interdisciplinary research in medicine is increasingly
      interested in cellular and molecular biology activity at the preclinical levels,
      utilizing molecular imaging methods on animal models. The task of integrated
      archiving, management, and distribution of these preclinical molecular imaging
      datasets at preclinical molecular imaging facilities is challenging due to
      disparate imaging systems and multiple off-site investigators. A Molecular
      Imaging Data Grid design, implementation, and initial evaluation is presented to
      demonstrate the secure and novel data grid solution for sharing preclinical
      molecular imaging data across the wide-area-network (WAN).

PMID- 20690001
TI  - Health-related quality of life in patients with myofascial pain syndrome.
AB  - Health-related quality of life is being emphasized because people who are living
      with a chronic illness are demanding that the qualities of their lives are
      enhanced. Health-related quality of life defines the effects of diseases or
      symptoms including musculoskeletal conditions on functioning and a sense of well
      being. This review highlights the results of quality-of-life measurements in
      patients with myofascial pain syndrome while providing a comparison with various
      musculoskeletal disorders, emphasizing the domains that are affected for each
      specific disease. Also, myofascial pain studies that included quality-of-life
      measurement as an outcome variable are considered.

PMID- 20690002
TI  - Central pain syndromes.
AB  - Central pain is a chronic neuropathic pain disorder that develops as a direct
      consequence of a lesion within the central nervous system. The most common causes
      for central pain are vascular lesions to the brain and the spinal cord, multiple
      sclerosis, and spinal cord injury. Clinically, central pain typically develops
      with a delay after the lesion. The pain typically is localized in an area of
      abnormal sensitivity corresponding to the preceding central lesion. Spontaneous
      pain and also evoked pains can be found. Pathophysiologically, ectopic neural
      activity and hyperexcitability are driven by pathological facilitatory and
      disinhibitory processes. In addition to medical history and clinical examination,
      diagnosis of central pain is based on imaging and electrophysiological
      techniques, including quantitative sensory testing, to confirm a central lesion
      and for identification of the underlying disease. Management of central pain
      mainly based on pharmacological treatment still is a great challenge, but
      evidence points to efficacy of antidepressants, anticonvulsants, and opioids.

PMID- 20690003
TI  - Prognostic markers in peripheral T-cell lymphoma.
AB  - Based on their own experience and knowledge of the literature, the authors review
      the pathobiological characteristics of peripheral T-cell lymphomas (PTCLs),
      focusing on the available prognostic indicators. The International Prognostic
      Index (IPI), which is based on age, performance status, lactate dehydrogenase
      [LDH], stage, and extranodal involvement, appears to be efficient as a prognostic
      index for PTCLs, at least in part and especially for certain PTCL subtypes.
      However, it is not so satisfactory for the two commonest PTCLs, PTCL not
      otherwise specified (PTCL/NOS) and angioimmunoblastic T-cell lymphoma (AITL), for
      which novel scores, possibly based on the biologic features of the tumors, have
      been explored. An Italian cooperative group proposed a revision of the IPI for
      PTCL unspecified (PTCL-U), the Prognostic Index for PTCL-U (PIT), which includes
      age, performance status, LDH, and bone marrow involvement. The PIT apparently
      offered some advantages, but they were not confirmed in subsequent studies. A
      clinical-biological score (the Bologna score) was then proposed, including tumor
      proliferation and clinical features (age, LDH, and performance status). This
      score appears promising and offers the intriguing advantage of integrating
      biological and clinical elements, but independent validation on a large series is
      still warranted. More recently, gene expression profiling has been used to
      identify novel molecular prognostic factors. In particular, inactivation of the
      NFkappaB pathway, high expression of proliferation-associated genes, and
      cytotoxic molecular phenotype seem to be associated with a worse outcome. So far,
      however, none of these indicators has been validated in an independent series.
      Finally, various reports have dealt specifically with the prognostication of NK
      derived tumors, including nasal and nasal-type lymphomas. Both the IPI and
      dedicated models have turned out to be of prognostic relevance for these tumors.
      In conclusion, although the IPI is somewhat effective for PTCL prognostication,
      novel scores that are more refined and possibly disease-specific are warranted.
      The validation process for several models, including clinical-pathological and
      molecular models, is now ongoing.

PMID- 20690004
TI  - Intestinal mesenchymal cells.
AB  - The non-white blood cell mesenchymal elements of the intestinal lamina propria
      are the myofibroblasts, fibroblasts, pericytes, stromal stem cells, muscularis
      mucosae, and the smooth muscle of the villus core associated with the lymphatic
      lacteal. We review the functional anatomy of these mesenchymal cells, what is
      known about their origin in the embryo and their replacement in adults, their
      putative role in intestinal mucosal morphogenesis, and the intestinal stem cell
      niche, and we consider new information about myofibroblasts as nonprofessional
      immune cells. Although our knowledge of the function of mesenchymal cells in
      intestinal disease is rudimentary, we briefly consider here their roles in cancer
      and intestinal inflammation.

PMID- 20690005
TI  - Colon ischemia: recent insights and advances.
AB  - Ischemic colitis is the most common manifestation of ischemic injury to the
      gastrointestinal tract, and the variety of defined causes is increasing. Local
      hypoperfusion and reperfusion injury are both thought to contribute to the
      disease process, which manifests with a wide spectrum of injury including
      reversible colopathy (subepithelial hemorrhage and edema), transient colitis,
      chronic colitis, stricture, gangrene, and fulminant universal colitis. The
      distribution is typically segmental. Older studies showed that any portion of the
      colon can be involved; recently, it was established that the site of involvement
      and prognosis can be correlated. In particular, isolated involvement of the right
      side of the colon was shown to have a different presentation and worse outcome
      than ischemic colitis involving other segments. Diagnosis is usually made
      clinically and supported by radiologic imaging and colonoscopic evaluation. Most
      patients respond to conservative supportive therapy, although some with severe
      disease require surgical intervention.

PMID- 20690006
TI  - Effectiveness of nebivolol and hydrochlorothiazide association on blood pressure,
      glucose, and lipid metabolism in hypertensive patients.
AB  - INTRODUCTION: Only 50% of hypertensive patients receive an appropriate treatment
      to normalize blood pressure (BP). Although monotherapy is often adequate in
      normalizing BP, it is sometimes necessary to start with combination therapy. The
      aim of the study was to evaluate the efficacy of nebivolol alone and in
      association with hydrochlorothiazide (HCT) in reducing BP in hypertensive
      patients with new-onset, mild-to-moderate hypertension, and to assess the effect
      of combination therapy on glucose and lipid metabolism. METHODS: At enrollment,
      patients underwent a full cardiovascular and metabolic evaluation. Patients were
      then prescribed nebivolol (5 mg/day). After 1 month, in those patients whose BP
      was not normalized, HCT 12.5 mg was added and increased further to 25 mg after 1
      month in those whose BP still was not normalized. All patients were assessed at
      monthly intervals for a further 5 months. RESULTS: We enrolled 233 treatment
      naive patients. After the first month of treatment with nebivolol, 70% of
      patients had normalized BP. The addition of HCT increased responder rates to 94%.
      An improvement in glucose metabolism was noted with nebivolol alone (at 1 month,
      the reduction in Homeostasis Model Assessment of Insulin Resistance [HOMA-IR] was
      26% and remained stable at 6 months); the adjunct of HCT blunted the reduction in
      HOMA-IR. No significant changes on lipid profile were noted with nebivolol,
      either alone or in combination therapy. CONCLUSION: Nebivolol is effective in
      mild-to-moderate hypertension and associated with favorable metabolic effects.
      The addition of HCT optimizes BP control in a high number of patients resistant
      to monotherapy without a negative impact on patients' glucose and lipid profile.

PMID- 20690007
TI  - Abstracts of the 46th General Assembly of the European Association for the Study
      of Diabetes (EASD). Stockholm, Sweden. September 20-24, 2010.

PMID- 20690008
TI  - Executive functioning characteristics associated with ADHD comorbidity in
      adolescents with disruptive behavior disorders.
AB  - The nature of executive dysfunction in youth with disruptive behavior disorders
      (DBD) remains unclear, despite extensive research in samples of children with
      attention-deficit hyperactivity disorder (ADHD). To determine the relationship
      between DBD, ADHD, and executive function deficits in aggressive teens,
      adolescents with DBD and comorbid ADHD (DBD + ADHD; n = 25), DBD without ADHD
      (DBD-ADHD; n = 23), and healthy controls (HC; n = 25) were compared on
      neurocognitive tests and questionnaires measuring executive functioning. Teens
      with DBD + ADHD performed worse on both neurocognitive and questionnaire measures
      of executive function than the DBD-ADHD and HC groups. Results suggest that
      subgroups of DBD may exist depending on the presence or absence of comorbid ADHD,
      which may have implications for the selection and efficacy of treatment
      strategies.

PMID- 20690010
TI  - [Not Available].

PMID- 20690009
TI  - Family routine moderates the relation between child impulsivity and oppositional
      defiant disorder symptoms.
AB  - Although child impulsivity is associated with oppositional defiant disorder (ODD)
      symptoms, few studies have examined whether family processes moderate this
      association. To address this gap, we tested whether child-reported family routine
      moderated the relation between child hyperactivity/impulsivity (HI) and ODD
      symptoms among a sample of low-income, urban, ethnic-minority children (N = 87,
      51% male). Child HI and ODD symptoms were assessed using parent and teacher
      reports. HI also was indexed by a laboratory task. Family routine was assessed
      using child self-report. Hierarchical regression analyses indicated that family
      routine moderated child HI. Among children with higher levels of teacher-reported
      HI symptoms, lower levels of family routine were associated with higher levels of
      teacher-reported ODD symptoms compared to children with lower levels of teacher
      reported HI symptoms. Children who self-reported higher levels of family routine
      were rated as low on teacher-reported ODD symptoms, regardless of teacher
      reported HI levels. Parent report and laboratory measures of child HI did not
      produce significant interactions. Lower levels of family routine may confer risk
      for ODD symptoms among low-income, urban, ethnic-minority children experiencing
      higher levels of HI.

PMID- 20690012
TI  - [Not Available].

PMID- 20690011
TI  - [Not Available].

PMID- 20690013
TI  - [Not Available].

PMID- 20690014
TI  - [Not Available].

PMID- 20690015
TI  - [Not Available].

PMID- 20690016
TI  - Screening of antifouling biocides around a pleasure boat marina in the Baltic Sea
      after legal restrictions.
AB  - Copper, zinc, and Irgarol 1051 concentrations were determined around a pleasure
      boat marina in the Stockholm Archipelago. Copper concentrations in water were
      twice as high (6.62 MUg L-1) in 2004 as 1992-1993, zinc concentrations six times
      higher (20.0 MUg L-1). Concentrations in bladder wrack (Fucus vesiculosus) had
      also risen. Irgarol concentrations in water were similar (~0.17 MUg L-1) in 1996
      and 2004, while concentrations in bladder wrack halved from 1993 to 2004. The
      peak concentrations of copper and Irgarol in water have shifted indicating that
      the main source in the 1990 s were local boats, but in 2004 visiting boats.

PMID- 20690017
TI  - Assessment of combined treatment of landfill urban solid waste leachate and
      sewage using Danio rerio and Daphnia similis.
AB  - The co-treatment from Morro do Ceu landfill leachate with domestic sewage in the
      Icarai STP was monitored with regard to the behavior of toxicity of its inflows
      and outflow. Leachate not exceeded 1.5% in volume in the plant. The acute
      ecotoxicological tests showed that, although leachate is far more harmful to D.
      rerio (LC50 approximately = 4) and D. similis (LC50 approximately = 5) than
      sewage (LC50 approximately = 62; LC50 approximately = 22), statistically the
      mixture of leachate with sewage did not result in a more toxic inflow (LC50
      approximately = 57; LC50 approximately = 12) for treatment than raw sewage. After
      treatment, the outflow toxicity (LC50 approximately = 76; LC50 approximately =
      16) complied with the environmental laws.

PMID- 20690018
TI  - Surgical approaches to epicardial pacemaker placement: does pocket location
      affect lead survival?
AB  - Permanent cardiac pacing in pediatric patients presents challenges related to
      small patient size, complex anatomy, electrophysiologic abnormalities, and
      limited access to cardiac chambers. Epicardial pacing currently remains the
      conventional technique for infants and patients with complex congenital heart
      disease. Pacemaker lead failure is the major source of failure for such
      epicardial systems. The authors hypothesized that a retrocostal surgical approach
      would reduce the rate of lead failure due to fracture compared with the more
      traditional subrectus and subxiphoid approaches. To evaluate this hypothesis, a
      retrospective chart review analyzed patients with epicardial pacemaker systems
      implanted or followed at Rady Children's Hospital San Diego between January 1980
      and May 2007. The study cohort consisted of 219 patients and a total of 620 leads
      with epicardial pacemakers. Among these patients, 84% had structural congenital
      heart disease, and 45% were younger than 3 years at time of the first
      implantation. The estimated lead survival was 93% at 2 years and 83% at 5 years.
      The majority of leads failed due to pacing problems (54%), followed by lead
      fracture (31%) and sensing problems (14%). When lead failure was adjusted for
      length of follow-up period, no significant differences in the rates of failure by
      pocket location were found.

PMID- 20690019
TI  - F-18 FDG uptake of bone marrow on PET/CT scan: it's correlation with CD38/CD138
      expressing myeloma cells in bone marrow of patients with multiple myeloma.
AB  - The percentage of myeloma cells in bone marrow is subsequently an important index
      of disease in patients with multiple myeloma (MM). Bone marrow myeloma cells can
      be detected by strong CD38/CD138 positivity and light scatter characteristics
      using flow cytometry. The aim of the study was to evaluate the relationship
      between the degree of F-18 fluorodeoxyglucose (F-18 FDG) uptake and the
      percentage of CD38/CD138 expressing myeloma cells in the bone marrow of patients
      with MM. A total of 31 patients with MM (14 females and 17 males, mean age 59.5
      +/- 1.9 years, range 29-80 years) were included in the study. All patients
      underwent FDG-positron emission tomography/computed tomography (PET/CT) scan
      within 2 weeks after the completion of the usual staging workup for MM,
      consisting of X-ray skeletal survey and hematological/biochemical parameters
      including complete blood count, liver and kidney function test, erythrocyte
      sedimentation rate, serum immunoglobulins, urine light chain excretion, C
      reactive protein, beta2-microglobulin, and bone marrow plasma cell infiltration.
      In all patients, flow cytometry was performed for assessing the percentage of
      CD38/CD138 expressing myeloma cells in the bone marrow samples. The extent of
      bone marrow FDG uptake on PET/CT scans was visually graduated using a qualitative
      scoring system as extension score (E-score) and also a semiquantitative scoring
      system defined as mean standardized uptake value (mSUV) of both femora. There was
      a statistically significant positive correlation between the percentage of
      CD38/CD138 expressing plasma cells in bone marrow and both mean qualitative (r =
      0.616) and semiquantitative (r = 0.755) results of F-18 FDG uptakes. mSUV and E
      score of bone marrow FDG uptake values were also correlated with serum beta-2
      microglobulin levels (r = 0.523 and r = 479, respectively). mSUV of bone marrow
      FDG uptake values were also negatively correlated with serum albumin levels (r = 
      0.424), whereas there was no correlation between E-score and albumin levels. In
      conclusion, our results indicate that increased F-18 FDG uptake of bone marrow is
      related to the percentage of plasma cell infiltration of bone marrow in patients
      with MM. Therefore, F-18 FDG-PET/CT study may be a useful tool for predicting the
      levels of myeloma cells in bone marrow, and an additional analysis of FDG uptake
      of bone marrow on FDG-PET/CT scans should be performed in patients undergoing PET
      studies during the initial staging, evaluating the therapy response, and
      monitoring patients with MM.

PMID- 20690020
TI  - Synovium tumor presenting as the first sign of IgD multiple myeloma.

PMID- 20690021
TI  - Endogenous cytokinins in Cocos nucifera L. in vitro cultures obtained from
      plumular explants.
AB  - Auxin induces in vitro somatic embryogenesis in coconut plumular explants through
      callus formation. Embryogenic calli and non-embryogenic calli can be formed from
      the initial calli. Analysis of endogenous cytokinins showed the occurrence of
      cytokinins with aromatic and aliphatic side chains. Fourteen aliphatic cytokinins
      and four aromatic cytokinins were analysed in the three types of calli and all
      the cytokinins were found in each type, although some in larger proportions than
      others. The most abundant cytokinins in each type of callus were
      isopentenyladenine-9-glucoside, zeatin-9-glucoside, zeatin riboside,
      isopentenyladenine riboside, dihydrozeatin and dihydrozeatin riboside in
      decreasing order. Total cytokinin content was compared between the three types of
      calli, and it was found to be lower in embryogenic calli compared to non
      embryogenic calli or initial calli. The same pattern was observed for individual
      cytokinins. When explants were cultured in media containing exogenously added
      cytokinins, the formation of embryogenic calli in the explants was reduced. When
      8-azaadenine (an anticytokinin) was added the formation of embryogenic calli and
      somatic embryos was increased. These results suggest that the difference in
      somatic embryo formation capacity observed between embryogenic calli and non
      embryogenic calli is related to their endogenous cytokinin contents.

PMID- 20690023
TI  - Operative treatment of avascular necrosis of the femoral head after slipped
      capital femoral epiphysis.
AB  - PURPOSE: The aim of the study was assessment of the medium-term outcome of
      operative treatment of avascular necrosis of the femoral head (ANFH) after
      slipped capital femoral epiphysis (SCFE). MATERIALS AND METHODS: Five patients
      were treated with valgus-flexion intertrochanteric osteotomy (VFITO) for partial
      ANFH that developed after operative treatment. Their average age at the time of
      slip was 12.5 years (range, 10-14); at the time of the reconstructive operation
      14 years (range, 12-16), the average interval between slip and the reconstructive
      operation was 14 months (range, 9-18). Partial ANFH was diagnosed between 6 and 8
      months after the slip on the basis of radiographic examination. In all the
      patients, the anterolateral third up to half of the femoral head was always
      affected. The average follow-up period was 73 months (range, 60-84). RESULTS:
      Comparison of MRI scans before and after VFITO proved resorption of the necrotic
      segment of the femoral head and its remodeling in all the five patients. The
      average preoperative Harris hip score (HHS) was 86 points, the average
      postoperative HHS was 94 points. CONCLUSION: VFITO provides a good outcome at
      medium-term follow-up in adolescent patients with partial ANFH after SCFE.

PMID- 20690022
TI  - Analysis of ascorbate peroxidase genes expressed in resistant and susceptible
      wheat lines infected by the cereal cyst nematode, Heterodera avenae.
AB  - Changes in ascorbate peroxidase (APX) enzyme activity in response to nematode
      (Heterodera avenae) attack were studied in roots of three hexaploid wheat lines
      carrying Cre2, Cre5, or Cre7 nematode resistance genes and the susceptible
      Triticum aestivum cv. Anza. A spectrophotometric analysis was carried out with
      root extracts of infected plants 4, 7, 11, and 14 days after nematode inoculation
      using uninfected plant as control. APX induction in infected resistant genotypes
      was similar and higher than in the susceptible control. The introgression
      wheat/Aegilops ventricosa H-93-8 line, carrying the Cre2 gene, and its parental
      line H-10-15 as susceptible control were used to analyze whether this increase of
      activity was correlated with the induction of APX gene expression. Genes encoding
      cytosolic forms of APX were induced in roots of both lines in response to
      nematode infection. This induction took place both earlier and with greater
      intensity in the resistant line than in the susceptible one, and it was also
      higher in the root area at the site of nematode attachment.

PMID- 20690024
TI  - Crosslinked polyethylene in knee arthroplasty: a simulator study evaluating the
      positive influence on the tribocontact area in the fixed-bearing knee.
AB  - BACKGROUND: Crosslinked polyethylene (XPE) was developed to reduce the wear rate
      in hip as well as knee arthroplasty. The crosslinking process reduces the
      mechanical properties of ultra-high-molecular-weight polyethylene (UHMWPE),
      particularly its fatigue strength. UHMWPE fatigue occurs more frequently in the
      knee than in the hip joint due to its changing tribocontact areas (TCAs) combined
      with high weight bearing. This is why XPE is still controversially discussed for
      use in total knee arthroplasty. Therefore, the potential advantage of using XPE
      in the knee was analysed in a simulator study with a focus on potential fatigue
      wear mechanisms. METHODS: Three different kinds of XPE and one conventional
      UHMWPE were tested over 5 million cycles in fixed-bearing knee designs. The TCAs
      were examined by replicas, and their extent was measured. The wear mechanism was
      analysed by scanning electron microscopy. RESULTS: The extent of the TCAs was
      less than 5% for all XPEs, whereas 35% for the conventional UHMWPE. Fatigue wear
      mechanisms were not observed. CONCLUSION: The measured small extent of the TCAs
      as a predictor of a low wear rate without any fatigue wear mechanism shows a
      possible advantage for the use of XPE even in knee arthroplasty.

PMID- 20690025
TI  - Surgical options for reconstruction of the extensor mechanism of the knee after
      limb-sparing sarcoma surgery: an evidence-based review.
AB  - BACKGROUND: Limb-salvage surgery remains current best practice for management of
      soft tissue and bony sarcomas about the knee, with the range of reconstructive
      options all providing reassuring levels of long-term survival and function. There
      is no current consensus as to the best method of reconstruction of the extensor
      mechanism of the knee (quadriceps-patellar complex), with a wide variety of
      options proposed. The techniques described in the literature include prosthetic
      reconstruction, soft tissue reconstruction (comprising reconstruction with
      pedicled muscle flaps or autogenous tendon grafts), and bony reconstructions
      (including vascularised fibula flaps). An evidence-based literature review
      assessing the available reconstructive options has not been undertaken. METHODS:
      A thorough literature review was undertaken, evaluating the current evidence
      regarding the use of surgical techniques for reconstruction of the extensor
      mechanism of the knee following oncologic resection. The literature identified
      was critically evaluated based on the current Oxford Centre for Evidence-Based
      Medicine definitions. RESULTS: There are no randomised trials in the literature
      in this setting, and thus no level 1 or level 2A studies to support any given
      technique. As such, there are many favourable techniques for reconstruction that
      have been well described and have some evidence base to support their use.
      Overall, there is a trend towards improved outcomes with biological
      reconstructive options, with lower reported levels of failure, infection and
      amputation. Despite this, no single technique has adequately proven to be
      superior. CONCLUSION: Given the proposed difficulties in randomising patients,
      good evidence for the optimal reconstructive choices may be hard to establish.

PMID- 20690026
TI  - Cellular response and extracellular matrix breakdown in rotator cuff tendon
      rupture.
AB  - PURPOSE: The aim of this study was to investigate the relationship between the
      disruption of ECM and cellular events including autophagic cell death, apoptosis
      and cell differentiation into myofibroblasts in the degenerative rotator cuff
      tendon. METHODS: Tendon samples were collected from 30 patients undergoing
      surgery for rotator cuff tears. Apoptosis, autophagic cell death and
      myofibroblasts of the tendon cells in the ruptured rotator cuff tendon were
      detected by immunohistochemical staining. The distribution of autophagic cell
      death, apoptosis, myofibroblasts and cell density were assessed and correlated
      with the disruption of ECM which was graded 0-3 points using a customized scoring
      system. RESULTS: The highest percentage of autophagic cell death (51.9 +/- 1.5%)
      was observed in grade 2 matrix, significantly different from that in matrix
      graded 0, 1 and 3 (P2Vs0 < 0.001; P2Vs1 < 0.001; P2Vs3 = 0.008, respectively).
      The highest apoptosis (34.8 +/- 1.6%) was found in grade 3 matrix (P3Vs0 < 0.001;
      P3Vs1 < 0.001; P3Vs2 = 0.044, respectively). The percentage of myofibroblasts
      significantly increased as the ECM degenerated, with the highest percentage in
      grade 3 matrix (19.8 +/- 1.3%) (P3Vs0 < 0.001; P3Vs11 < 0.001; P3Vs2 = 0.044,
      respectively). The total cell density varied with the grade of ECM, with maximum
      cell density in the matrix that was graded 1 (674 +/- 27) and minimum cell
      density in matrix 3 area (395 +/- 17) (P1Vs3 < 0.001). CONCLUSION: This study
      indicates that autophagic cell death, apoptosis and myofibroblast cell
      differentiation occur in ruptured rotator cuff tissue. These cellular events are
      closely related to the extent of damage to the ECM structure.

PMID- 20690027
TI  - Clinical tests for carpal tunnel syndrome in contemporary practice.
AB  - INTRODUCTION: A study conducted to establish the most accurate combination of
      questionnaire and physical signs for the diagnosis of carpal tunnel syndrome.
      METHOD: Nerve conduction studies confirmed 70 patients with having carpal tunnel
      syndrome who were enrolled along with 70 age- and sex-matched controls. Patients
      were assessed using a symptom questionnaire, Phalen's test, Hoffmann-Tinel's
      sign, hand elevation test, carpal compression test, tourniquet test, pressure
      aesthesiometry and two-point discrimination. RESULTS: Through multivariate
      analysis, the best combination of tests was tourniquet, carpal compression and
      Phalen's tests but the difference between these and hand elevation test alone was
      negligible. CONCLUSION: The hand elevation test may be used in isolation and is
      superior to questionnaires and other physical signs in the clinical diagnosis of
      carpal tunnel syndrome.

PMID- 20690028
TI  - Comparative immunolocalisation of perlecan with collagen II and aggrecan in human
      foetal, newborn and adult ovine joint tissues demonstrates perlecan as an early
      developmental chondrogenic marker.
AB  - We undertook a comparative immunolocalisation study on type II collagen, aggrecan
      and perlecan in a number of 12- to 14-week-old human foetal and postnatal (7-19
      months) ovine joints including finger, toe, knee, elbow, hip and shoulder. This
      demonstrated that perlecan followed a virtually identical immunolocalisation
      pattern to that of type II collagen in the foetal tissues, but a slightly
      divergent localisation pattern in adult tissues. Aggrecan was also localised in
      the cartilaginous joint tissues, which were clearly delineated by toluidine blue
      staining and the type II collagen immunolocalisations. It was also present in the
      capsular joint tissues and in ligaments and tendons in the joint, which stained
      poorly or not at all with toluidine blue. In higher power microscopic views,
      antibodies to perlecan also stained small blood vessels in the synovial lining
      tissues of the joint capsule; however, this was not discernable in low power
      macroscopic views where the immunolocalisation of perlecan to pericellular
      regions of cells within the cartilaginous rudiments was a predominant feature.
      Perlecan was also evident in small blood vessels in stromal connective tissues
      associated with the cartilage rudiments and with occasional nerves in the
      vicinity of the joint tissues. Perlecan was expressed by rounded cells in the
      enthesis attachment points of tendons to bone and in rounded cells in the inner
      third of the meniscus, which stained prominently with type II collagen and
      aggrecan identifying the chondrogenic background of these cells and local
      compressive loads. Flattened cells within the tendon and in the surface laminas
      of articular cartilages and the meniscus did not express perlecan. Collected
      evidence presented herein, therefore, indicates that besides being a basement
      membrane component, perlecan is also a marker of chondrogenic cells in prenatal
      cartilages. In postnatal cartilages, perlecan displayed a pericellular
      localisation pattern rather than the territorial or interterritorial localisation
      it displayed in foetal cartilages. This may reflect processing of extracellular
      perlecan presumably as a consequence of intrinsic biomechanical loading on these
      tissues or to divergent functions for perlecan and type II collagen in adult
      compared to prenatal tissues.

PMID- 20690029
TI  - DkMyb2 wound-induced transcription factor of persimmon (Diospyros kaki Thunb.),
      contributes to proanthocyanidin regulation.
AB  - Proanthocyanidins (PAs) are secondary metabolites that contribute to the
      protection of a plant against biotic and abiotic stresses. Persimmon (Diospyros
      kaki) accumulates abundant PAs in each plant organ, and some potential Myb-like
      transcription factors (Myb-TFs) involved in the production of PAs have been
      isolated. In this study, we aimed to molecularly characterize one of them,
      DkMyb2, which was placed in a subclade including a PA regulator of Arabidopsis
      (Arabidopsis thaliana), TRANSPARENT TESTA2 (TT2), and was co-induced with PA
      pathway genes after wound stress. Ectopic DkMyb2 overexpression caused
      significant up-regulation of PA pathway genes in transgenic persimmon calluses
      and significant accumulation of PA, and increased mean degree of polymerization
      of PAs in transgenic kiwifruit calluses. Analysis of the DNA-binding ability of
      DkMyb2 by electrophoretic mobility shift assays showed that DkMyb2 directly binds
      to the AC-rich cis-motifs known as AC elements in the promoters of the two PA
      pathway genes in persimmon, DkANR, and DkLAR. Furthermore, a transient reporter
      assay using a dual-luciferase system demonstrated direct transcriptional
      activation of DkANR and DkLAR by DkMyb2. We also discuss subfunctionalization of
      two PA regulators in persimmon, DkMyb2 and DkMyb4, as well as PA regulators in
      other plant species from the viewpoint of their ability to bind to cis-motifs and
      their functions in transcriptional activation. Our results provide insight into
      the multiple regulatory mechanisms that control PA metabolism by Myb-TFs in
      persimmon.

PMID- 20690030
TI  - Functional mapping of quantitative trait loci associated with rice tillering.
AB  - Several biologically significant parameters that are related to rice tillering
      are closely associated with rice grain yield. Although identification of the
      genes that control rice tillering and therefore influence crop yield would be
      valuable for rice production management and genetic improvement, these genes
      remain largely unidentified. In this study, we carried out functional mapping of
      quantitative trait loci (QTLs) for rice tillering in 129 doubled haploid lines,
      which were derived from a cross between IR64 and Azucena. We measured the average
      number of tillers in each plot at seven developmental stages and fit the growth
      trajectory of rice tillering with the Wang-Lan-Ding mathematical model. Four
      biologically meaningful parameters in this model--the potential maximum for
      tiller number (K), the optimum tiller time (t(0)), and the increased rate (r), or
      the reduced rate (c) at the time of deviation from t(0)--were our defined
      variables for multi-marker joint analysis under the framework of penalized
      maximum likelihood, as well as composite interval mapping. We detected a total of
      27 QTLs that accounted for 2.49-8.54% of the total phenotypic variance. Nine
      common QTLs across multi-marker joint analysis and composite interval mapping
      showed high stability, while one QTL was environment-specific and three were
      epistatic. We also identified several genomic segments that are associated with
      multiple traits. Our results describe the genetic basis of rice tiller
      development, enable further marker-assisted selection in rice cultivar
      development, and provide useful information for rice production management.

PMID- 20690031
TI  - Alpha-synuclein aggregation is involved in the toxicity induced by ferric iron to
      SK-N-SH neuroblastoma cells.
AB  - Increased nigral iron levels and intracytoplasmic Lewy bodies (LBs) in the
      degenerating neurons are found in Parkinson's disease (PD). Whether LBs formation
      is involved in the toxicity of iron is largely unknown. In the present study, we
      observed that the toxicity of ferric iron was enhanced when SK-N-SH cells were
      overexpressed with wild-type alpha-synuclein. The mitochondrial transmembrane
      potential (Deltapsi(m)) and cell viability were decreased in these cells, while
      the intracellular reactive oxygen species (ROS) were increased, compared with
      that of control. More aggregated alpha-synuclein was observed in these cells.
      However, while silencing the expression of alpha-synuclein in SK-N-SH cells with
      siRNA, iron-induced toxicity could be partially alleviated, indicated by the
      returned Deltapsi(m) and cell viability and reduced ROS formation compared with
      that of control. No alpha-synuclein aggregation could be observed in these cells.
      The results suggest that alpha-synuclein aggregation was involved in the toxicity
      of iron to SK-N-SH neuroblastoma cells. Targeting the aggregation of alpha
      synuclein might provide a therapeutic strategy for PD in the future.

PMID- 20690032
TI  - Plasma levels of vascular endothelial growth factor and fibroblast growth factor
      2 in patients with major depressive disorders.
AB  - We investigated the plasma levels of VEGF and FGF-2, important factors for
      regulation of neuroplasticity such as neurogenesis, in patients in remission from
      major depressive disorders (MDD). The plasma VEGF levels were significantly
      higher in the MDD patients than in the matched control subjects, while no
      significant difference in plasma FGF-2 levels was found. In particular, the MDD
      patients with family history of psychiatric disorders, but not patients without
      such a family history, showed significantly higher values of plasma VEGF than the
      controls. Although this is a preliminary study, altered VEGF levels might be
      involved in the pathophysiology of MDD.

PMID- 20690033
TI  - Does the transcription factor AP-2beta have an impact on the genetic and early
      environmental influence on ethanol consumption?
AB  - Genes involved in alcoholism have consensus sites for the transcription factor
      activator protein (TFAP) 2beta. In the present study, we investigated TFAP-2beta
      protein levels in the ethanol-preferring alko, alcohol (AA) and the ethanol
      avoiding alko, non-alcohol (ANA) rat lines. Furthermore, basal and ethanol
      induced TFAP-2beta levels were examined in Wistar rats exposed to different early
      postnatal environments that are known to affect later ethanol consumption. Taken
      together, we found differences in brainstem TFAP-2beta protein between the AA and
      ANA rats.

PMID- 20690034
TI  - Soluble receptor activator of nuclear factor-kappaB ligand (RANKL) and
      osteoprotegerin in ankylosing spondylitis: OPG is associated with poor physical
      mobility and reflects systemic inflammation.
AB  - The objective of the study was to investigate the role of receptor activator of
      nuclear factor-kappaB ligand (RANKL) and osteoprotegerin (OPG) in ankylosing
      spondylitis (AS). Serum levels of soluble RANKL (sRANKL) and OPG were measured in
      42 AS patients and 26 healthy controls. We evaluated the AS patient's disease
      activity, functional ability, global assessment, and physical mobility and tested
      markers of systemic inflammation, erythrocyte sedimentation rate (ESR), and C
      reactive protein (CRP) levels. Serum levels of sRANKL [mean (SD), 4.75 (1.88) vs.
      3.70 (1.14) pmol/l, p = 0.015] and OPG [mean (SD), 5.18 (1.19) vs. 4.52 (0.85)
      pmol/l, p = 0.026] were significantly higher in the 42 AS patients than the 26
      healthy controls. Interestingly, serum OPG levels correlated significantly with
      ESR (r = 0.417, p = 0.007), CRP (r = 0.524, p < 0.001), tragus-to-wall distance
      (r = 0.556, p < 0.001), fingertip-to-floor distance (r = 0.423, p = 0.007), and
      occiput-to-wall distance (r = 0.465, p = 0.002) and correlated inversely with
      modified Schober index (r = -0.525, p = 0.001), cervical rotation (r = -0.403, p
      = 0.022), lateral lumbar flexion (r = -0.587, p < 0.001), and chest expansion (r
      = -0.553, p < 0.001). Moreover, in the AS patients with higher (> or =4.925
      pmol/l, n = 21) serum OPG levels, there were significant increases in the tragus
      to-wall distance (p = 0.007), fingertip-to-floor distance (p = 0.023), and CRP
      levels (p = 0.014) and decreased in the modified Schober index (p = 0.012),
      lateral lumbar flexion (p = 0.019), and chest expansion (p = 0.005). Serum levels
      of sRANKL and OPG are increased in the AS patients and may participate in the
      disease process of AS. Production of OPG has association with poor physical
      mobility and may reflect systemic inflammation in AS.

PMID- 20690035
TI  - Sterol binding by OSBP-related protein 1L regulates late endosome motility and
      function.
AB  - ORP1L is an oxysterol binding homologue that regulates late endosome (LE)
      positioning. We show that ORP1L binds several oxysterols and cholesterol, and
      characterize a mutant, ORP1L Delta560-563, defective in oxysterol binding. While
      wild-type ORP1L clusters LE, ORP1L Delta560-563 induces LE scattering, which is
      reversed by disruption of the endoplasmic reticulum (ER) targeting FFAT motif,
      suggesting that it is due to enhanced LE-ER interactions. Endosome motility is
      reduced upon overexpression of ORP1L. Both wild-type ORP1L and the Delta560-563
      mutant induce the recruitment of both dynactin and kinesin-2 on LE. Most of the
      LE decorated by overexpressed ORP1L fail to accept endocytosed dextran or EGF,
      and the transfected cells display defective degradation of internalized EGF.
      ORP1L silencing in macrophage foam cells enhances endosome motility and results
      in inhibition of [(3)H]cholesterol efflux to apolipoprotein A-I. These data
      demonstrate that LE motility and functions in both protein and lipid transport
      are regulated by ORP1L.

PMID- 20690036
TI  - Effect of Ni2+ and Cd2+ ions on thermally induced conformational transitions in
      poly(dA)-poly(dT) system.
AB  - Effects of Ni(2+) and Cd(2+) ions on thermally induced conformational transitions
      in the poly(dA).poly(dT) polynucleotide duplex and poly(dA).2poly(dT) triplex
      under near physiological ionic conditions were studied by measurement of UV
      absorption melting curves and static light scattering intensity. The diagrams of
      conformational transitions in poly(dA)-poly(dT)-Me(2+) systems were plotted. An
      aggregation in these polynucleotide systems arises at certain values of the metal
      ions concentration and the temperature after the polymer dissociation into single
      strands. The phenomenon is conditioned by the aggregation of poly(dA) via the
      interstrand cross-linking by the dication bridges. Unlike Ni(2+), Cd(2+) induces
      formation of very stable aggregates which did not disintegrate even upon cooling
      up to room temperature.

PMID- 20690037
TI  - Social connections, trajectories of hopelessness, and serious violence in
      impoverished urban youth.
AB  - Youth living in impoverished urban neighborhoods are at risk for becoming
      hopeless about their future and engaging in violent behaviors. The current study
      seeks to examine the longitudinal relationship between social connections,
      hopelessness trajectories, and subsequent violent behavior across adolescence.
      Our sample included 723 (49% female) African American youth living in
      impoverished urban neighborhoods who participated in the Mobile Youth Survey from
      1998 through 2006. Using general growth mixture modeling, we found two
      hopelessness trajectory classes for both boys and girls during middle
      adolescence: a consistently low hopelessness class and an increasingly hopeless
      class with quadratic change. In all classes, youth who reported stronger early
      adolescent connections to their mothers were less hopeless at age 13. The
      probability of later adolescent violence with a weapon was higher for boys and
      was associated with the increasingly hopeless class for both boys and girls.
      Implications for new avenues of research and design of hope-based prevention
      interventions will be discussed.

PMID- 20690038
TI  - Maternal marital status and birth outcomes: a systematic review and meta
      analyses.
AB  - Systematically review risks of an infant being born with low birth weight (LBW),
      preterm birth (PTB) or small for gestational age (SGA) among married and
      unmarried women. Medline, Embase, CINAHL, and bibliographies of identified
      articles were searched for English language studies. Studies reporting birth
      outcomes of married and unmarried (single and cohabitant) were included. Two
      reviewers independently collected data and assessed the quality of the studies
      for biases in sample selection, exposure assessment, confounder, analytical,
      outcome assessments, and attrition. Meta-analyses were performed using random
      effect model for both unadjusted and adjusted data and odds ratio (OR), and 95%
      confidence interval (CI) were calculated. Twenty-one studies of low to moderate
      risk of bias were included. Compared to married mothers unadjusted odds of (a)
      LBW was increased among unmarried (OR 1.46, 95%CI 1.25-1.71), single (OR 1.65,
      95%CI 1.44-1.88) and cohabitating (OR 1.29, 95%CI 1.25-1.32) mothers; (b) PTB was
      increased among unmarried (OR 1.22, 95%CI 1.14-1.31), single (OR 1.54, 95%CI 1.39
      1.72) and cohabitating (OR 1.15, 95%CI 1.08-1.23) mothers and (c) SGA birth was
      increased among unmarried (OR 1.45, 95%CI 1.32-1.61), single (OR 1.70, 95%CI 1.47
      1.97) and cohabitating (OR 1.36, 95%CI 1.30-1.42) mothers. Meta-analyses of
      adjusted odds estimates confirmed these findings at marginally lower odds.
      Maternal unmarried status is associated with an increased risk of LBW, PTB and
      SGA births.

PMID- 20690039
TI  - Predicting skeletal complications in metastatic breast cancer raises challenges.

PMID- 20690040
TI  - Gray matter reduction associated with systemic chemotherapy for breast cancer: a
      prospective MRI study.
AB  - Brain gray matter alterations have been reported in cross-sectional magnetic
      resonance imaging (MRI) studies of breast cancer patients after cancer treatment.
      Here we report the first prospective MRI study of women undergoing treatment for
      breast cancer, with or without chemotherapy, as well as healthy controls. We
      hypothesized that chemotherapy-associated changes in gray matter density would be
      detectable 1 month after treatment, with partial recovery 1 year later.
      Participants included breast cancer patients treated with (CTx+, N = 17) or
      without (CTx-, N = 12) chemotherapy and matched healthy controls (N = 18). MRI
      scans were acquired at baseline (after surgery but before radiation,
      chemotherapy, and/or anti-estrogen treatment), 1 month after completion of
      chemotherapy (M1), and 1 year later (Y1). Voxel-based morphometry (VBM) was used
      to evaluate gray matter density differences between groups and over time. There
      were no between-group gray matter differences at baseline. Group-by-time
      interactions showed declines from baseline to M1 in both cancer groups relative
      to controls. Within-group analyses indicated that at M1 relative to baseline the
      CTx+ group had decreased gray matter density in bilateral frontal, temporal, and
      cerebellar regions and right thalamus. Recovery was seen at Y1 in some regions,
      although persistent decreases were also apparent. No significant within-group
      changes were found in the CTx- or control groups. Findings were not attributable
      to recency of cancer surgery, disease stage, psychiatric symptoms, psychotropic
      medication use, or hormonal treatment status. This study is the first to use a
      prospective, longitudinal approach to document decreased brain gray matter
      density shortly after breast cancer chemotherapy and its course of recovery over
      time. These gray matter alterations appear primarily related to the effects of
      chemotherapy, rather than solely reflecting host factors, the cancer disease
      process, or effects of other cancer treatments.

PMID- 20690041
TI  - Male labor migrants in Russia: HIV risk behavior levels, contextual factors, and
      prevention needs.
AB  - Although the dire life circumstances of labor migrants working in Russia are well
      known, their HIV risk vulnerability and prevention needs are understudied. Low
      socioeconomic status, lack of access to services, separation from family, and
      limited risk awareness all contribute to migrants' HIV vulnerability. Male labor
      migrants in St. Petersburg (n = 499) were administered assessments of their
      sexual behavior practices, substance use, and psychosocial characteristics
      related to risk and well-being. Thirty percent of migrants reported multiple
      female partners in the past 3 months. Condom use was low, ranging from 35% with
      permanent to 52% with casual partners. Central Asian migrants had very low AIDS
      knowledge, low levels of substance use, moderate sexual risk, high depression,
      and poor social supports. Eastern European migrants had higher AIDS knowledge,
      alcohol and drug use, and sexual risk. Improved HIV prevention efforts are needed
      to reduce the risk vulnerability of migrants who relocate to high disease
      prevalence areas.

PMID- 20690042
TI  - Callus induction and plant regeneration in Alternanthera philoxeroides.
AB  - To establish a successful in vitro plant regeneration system in Alternanthera
      philoxeroides (Mart.) Griseb, an orthogonal design was used to investigate the
      effects of three factors (plant growth regulators, explant types and dark
      treatment in initial-stage), each having three levels. The effects of these
      factors and levels on callus induction and shoot regeneration were quantitatively
      evaluated by analysis of variance. The experimental results showed that the
      callus induction was significantly affected by 2, 4-dichlorophenoxyacetic acid
      (2, 4-D), and shoot differentiation from subcultured pieces of callus was
      enhanced mostly by dark treatment in initial-stage. The optimal conditions for
      callus induction are obtained from the stem explants cultured on semi-solid
      Murashige and Skoog (MS) medium plus 2.2 MUM BA and 2.2 MUM 2, 4-D, with 20 days
      dark treatment in initial-stage. The highest frequency of shoot regeneration is
      obtained from the calli cultured on semi-solid MS medium plus 8.8 MUM BA, without
      dark treatment in initial-stage.

PMID- 20690043
TI  - The New York Consortium on Membrane Protein Structure (NYCOMPS): a high
      throughput platform for structural genomics of integral membrane proteins.
AB  - The New York Consortium on Membrane Protein Structure (NYCOMPS) was formed to
      accelerate the acquisition of structural information on membrane proteins by
      applying a structural genomics approach. NYCOMPS comprises a bioinformatics
      group, a centralized facility operating a high-throughput cloning and screening
      pipeline, a set of associated wet labs that perform high-level protein production
      and structure determination by x-ray crystallography and NMR, and a set of
      investigators focused on methods development. In the first three years of
      operation, the NYCOMPS pipeline has so far produced and screened 7,250 expression
      constructs for 8,045 target proteins. Approximately 600 of these verified targets
      were scaled up to levels required for structural studies, so far yielding 24
      membrane protein crystals. Here we describe the overall structure of NYCOMPS and
      provide details on the high-throughput pipeline.

PMID- 20690044
TI  - Real-time estimation of cerebrospinal fluid system parameters via oscillating
      pressure infusion.
AB  - Hydrocephalus is related to a disturbed cerebrospinal fluid (CSF) system. For
      diagnosis, lumbar infusion test are performed to estimate outflow conductance, C
      (out), and pressure volume index, PVI, of the CSF system. Infusion patterns and
      analysis methods used in current clinical practice are not optimized. Minimizing
      the investigation time with sufficient accuracy is of major clinical relevance.
      The aim of this study was to propose and experimentally evaluate a new method,
      the oscillating pressure infusion (OPI). The non-linear model of the CSF system
      was transformed into a linear time invariant system. Using an oscillating
      pressure pattern and linear system identification methods, C (out) and PVI with
      confidence intervals, were estimated in real-time. Forty-two OPI and constant
      pressure infusion (CPI) investigations were performed on an experimental CSF
      system, designed with PVI = 25.5 ml and variable C (out). The ARX model robustly
      estimated C (out) (mean C (out,OPI) - C (out,CPI) = 0.08 MUl/(s kPa), n = 42, P =
      0.68). The Box-Jenkins model proved most reliable for PVI (23.7 +/- 2.0 ml, n =
      42). The OPI method, with its oscillating pressure pattern and new parameter
      estimation methods, efficiently estimated C (out) and PVI as well as their
      confidence intervals in real-time. The results from this experimental study show
      potential for the OPI method and supports further evaluation in a clinical
      setting.

PMID- 20690045
TI  - Lithium chloride regulation of the substance P encoding preprotachykinin a, Tac1
      gene in rat hippocampal primary cells.
AB  - In rat hippocampal cultures, the preprotachykinin A (PPTA/Tac1) gene, which
      encodes the neuropeptide substance P, is regulated by the action of lithium. We
      used reporter gene and expression constructs to demonstrate that this mechanism
      of action of lithium is mediated via a previously characterised cis-regulatory
      Ebox element in the proximal promoter, which binds members of the basic Helix
      Loop-Helix family of transcription factors. Consistent with this, in hippocampal
      cells, both the expression of the endogenous gene and the function of this
      promoter element are differentially regulated by the basic Helix-Loop-Helix
      factors, upstream stimulatory factor 1 and 2 (USF1/2). In addition, the genes for
      USF1 and USF2 are differentially regulated by lithium in these cells. Our data
      implicate USF1 as a major regulator of the action of lithium on the proximal PPTA
      promoter.

PMID- 20690046
TI  - Epstein-barr virus-associated smooth muscle tumor of the larynx: report of a rare
      case mimicking leiomyosarcoma.
AB  - We present a patient (male 54 years) with a history of renal transplant who 14
      years post transplantation developed a symptomatic (stridor) laryngeal Epstein
      Barr virus (EBV)-associated smooth muscle tumor (EBV-SMT) in the absence of
      concomitant disease elsewhere. Nine years post transplantation the patient
      developed a subcutaneous EBV-SMT tumor located on the calf. The laryngeal tumor
      displayed low-grade nuclear atypia and was infiltrating into the surrounding soft
      tissue, focally ulcerating through the overlying epithelium. Histologic features
      included: neoplastic cells with myoid differentiation, a component of primitive
      appearing small mesenchymal cells with hyperchromatic nuclei, mitotic activity,
      intralesional small to medium sized blood vessels and T-lymphocytes. Both the
      myoid and small cell mesenchymal components strongly expressed smooth muscle
      actin and h-caldesmon, but not desmin, cytokeratins, CD34 or S-100 protein. There
      was strong positive nuclear reaction for EBV-RNA on in situ hybridization (EBER).
      No other tumor was detected on clinical and radiological examinations and no
      evidence of tumor in other sites, over 8 months of follow-up, till death was
      detected. This case emphasizes the importance of considering this pathologic
      entity when solitary smooth muscle actin-expressing tumors are encountered in the
      larynx of immunocompromised patients.

PMID- 20690047
TI  - Applications of tissue microarray technology.
AB  - Tissue microarrays (TMAs) have become a standard tool for tissue-based research
      during the last decade. In cancer research, depending on the available data
      attached to the arrayed tissue, three main types of arrays are commonly
      manufactured. Prevalence TMAs have no further data available and are suited to
      estimate the frequency of the occurrence of a particular alteration. Progression
      arrays include tissues of different stages of disease, and are instrumental to
      study the role of a marker protein for tumor initiation, progression, or
      metastatic growth. Prognosis TMAs contain tissues with patient follow-up data.
      These TMAs are the key to uncover the clinical impact of molecular markers. In
      combination with normal tissue arrays representing healthy tissues, prevalence,
      progression, and prognosis TMAs allow for a rapid and comprehensive analysis of
      molecular markers in human cancers. TMAs are also successfully used for many
      noncancer applications, such as Alzheimer's or inflammatory disease research.

PMID- 20690048
TI  - Quality aspects of TMA analysis.
AB  - The quality of a TMA experiment can only be as good as the worst step in the
      entire process. Making and analyzing of tissue microarrays (TMAs) is a complex
      process involving tissue sample acquisition and preparation, expert histological
      diagnosis, long-term collection of clinical data, development of suitable
      laboratory protocols, the microscopic analysis, and the statistical analysis of
      the experiment. The quality of all these factors equally influences the outcome
      of TMA studies.

PMID- 20690049
TI  - Representativity of TMA studies.
AB  - The smaller the portion of a tumor sample that is analyzed becomes, the higher is
      the risk of missing important histological or molecular features that might be
      present only in a subset of tumor cells. Many researchers have, therefore,
      suggested using larger tissue cores or multiple cores from the same donor tissue
      to enhance the representativity of TMA studies. However, numerous studies
      comparing the results of TMA studies with the findings from conventional large
      sections have shown that all well-established associations between molecular
      markers and tumor phenotype or patient prognosis can be reproduced with TMAs even
      if only one single 0.6 mm tissue spot is analyzed. Moreover, the TMA technology
      has proven to be superior to large section analysis in finding new clinically
      relevant associations. The high number of samples that are typically included in
      TMA studies, and the unprecedented degree of standardization during TMA
      experiments and analysis often give TMA studies an edge over traditional large
      section studies.

PMID- 20690050
TI  - Recipient block TMA technique.
AB  - New high-throughput screening technologies have led to the identification of
      hundreds of genes with a potential role in cancer or other diseases. One way to
      prioritize the leads obtained in such studies is to analyze a large number of
      tissues for candidate gene expression. The TMA methodology is now an established
      and frequently used tool for high-throughput tissue analysis. The recipient block
      technology is the "classical" method of TMA making. In this method, minute
      cylindrical tissue punches typically measuring 0.6 mm in diameter are removed
      from donor tissue blocks and are transferred into empty "recipient" paraffin
      blocks. Up to 1,000 different tissues can be analyzed in one TMA block. The
      equipment is affordable and easy to use in places where basic skills in histology
      are available.

PMID- 20690051
TI  - Protocol for constructing tissue arrays by cutting edge matrix assembly.
AB  - We present a protocol for construction of high-density tissue microarrays,
      cutting edge matrix assembly, which is based on repetitive sectioning and bonding
      of tissues. Maximized array density is achieved by a scaffold-free, self
      supporting construction with rectangular array features that are bonded edge-to
      edge, resulting in minimal wasted space between samples. Construction of the
      tissue array blocks from paraffin-embedded tissue involves initial bonding of
      primary tissue plates into multiple primary tissue stacks. This is achieved by
      taking a shaving of desired thickness from the face of each specimen block,
      trimming the shavings into a set of rectangular primary tissue plates, and
      bonding multiple plates into primary stacks of tissue. Each resulting primary
      tissue stack is then transversely cut to produce a set of secondary tissue plates
      that contains elements of each tissue represented in the primary stacks.
      Secondary plates from multiple primary sample stacks are then restacked and
      bonded into a secondary stack. The assembled secondary stack represents a
      laminate of laminates, which becomes the final array block. The final array block
      is then reembedded in paraffin and can be sectioned transversely using a
      microtome to yield micrometer thin sections that are transferred to glass slides
      for array display and analysis. This technology has facilitated the construction
      of arrays containing more than 10,000 tissue features on a standard glass slide.

PMID- 20690052
TI  - Hypodermic needle without recipient paraffin block technique.
AB  - This technique allows building TMA blocks with more than 300 tissue cores without
      using a recipient paraffin block for the tissue cores and without using a
      commercial TMA builder instrument. It is based on the construction of TMA needles
      modifying conventional hypodermic needles to punch tissue cores from donor
      blocks. Tissue cores are punctured from donor blocks and attached by double-sided
      adhesive tape on a computer-generated paper grid used to align the cores on the
      block mold, which is filled with liquid paraffin. TMA blocks constructed using
      this method can be utilized as positive and negative controls for
      immunohistochemistry, histochemistry and other techniques, interlaboratory
      quality control and also in research, but never for diagnosis purposes. This
      technique has the following advantages: it is easy to reproduce, affordable,
      quick, and creates uniform blocks with more than 300 cores aligned, at the same
      plane, adherent, and easy to cut, with negligible losses during conventional
      cutting and technical procedures.

PMID- 20690053
TI  - Resin technologies: construction and staining of resin TMA's.
AB  - The traditional formaldehyde-fixed paraffin-embedded tissue, and therefore the
      tissue microarrays created from it, provide good morphology but with a
      compromised antigenicity when compared to frozen tissue. In contrast, while
      solving the issue of antigenicity, frozen tissue suffers from a lack of
      morphology. We have demonstrated that tissue microarrays constructed in glycol
      methacrylate resin, when combined with a cold acetone fixation step, have been
      able to combine the superior morphology of resin-embedded sections with the
      superior antigenicity of frozen tissue for prospectively collected material.

PMID- 20690054
TI  - Tissue microarrays from frozen tissues-OCT technique.
AB  - Tissue microarray technology is a new method used to analyze 100s to 1,000s of
      tumor samples on a single slide allowing high throughput analysis of genes and
      proteins on a large cohort. The original methodology involves coring tissues from
      paraffin-embedded tissue donor blocks and placing them into a single paraffin
      block. One difficulty with paraffin-embedded tissue relates to antigenic changes
      in proteins and mRNA degradation induced by the fixation and embedding process.
      We modified this technology by using frozen tissues embedded in OCT compound as
      donor samples and arraying the specimens into a recipient OCT block. Tumor tissue
      is not fixed before embedding, and sections from the array are evaluated without
      fixation or postfixed according to the appropriate methodology used to analyze a
      specific gene at the DNA, RNA, and/or protein levels. While paraffin tissue
      arrays can be problematic for immunohistochemistry and for RNA in situ
      hybridization analyses, this method allows optimal evaluation by each technique
      and uniform fixation across the array panel. Frozen tissue microarrays work well
      for DNA, RNA, and protein analyses, and may have significant advantages over the
      original technology for the assessment of some genes and proteins by improving
      both qualitative and quantitative results.

PMID- 20690055
TI  - An alternative technology to prepare tissue microarray using frozen tissue
      samples.
AB  - Although most tissue microarray (TMA) slides are currently made from paraffin
      embedded tissues, -frozen clinical tissues are also gradually being used to
      prepare TMAs. This is because frozen tissues contain better quality RNAs and
      proteins for profiling gene expressions. Here, we introduce another TMA method
      that is applicable to a broader range of frozen tissue samples.In this method, an
      agarose-gel-based array recipient block is first made using several simple
      instruments. Frozen donor tissues are then manually cored and arrayed into the
      recipient block array at -10 degrees C. After arraying, the array block can be
      immediately sectioned on a cryostat microtome to make TMA slides for in situ
      hybridization and immunocytochemistry studies. TMAs made by this method have well
      defined array configurations, good tissue/cell morphology, and well-preserved
      proteins and mRNAs. This low-cost and time-saving method provides an alternative
      tool for preparing high quality TMAs for gene expression analyses.

PMID- 20690056
TI  - Building "tissue" microarrays from suspension cells.
AB  - Tissue microarray (TMA) is a highly efficient method that allows for large-scale
      measurement of -expression of RNA or protein in multiple tissue sections
      simultaneously. Most TMAs are made from paraffin--embedded tissues. In this
      chapter, we detail a method that enables construction of TMAs from small volumes
      of cells in suspension. A TMA is built using pellets of 1 x 10(6) to 5 x 10(7)
      spun cells after fixation, processing, and embedding. The entire procedure is
      carried out in a microcentrifuge tube and yields excellent preservation of
      cytomorphology and immunoreactivity from both fresh and frozen suspension cells.
      It is particularly useful for the study of hematopoietic neoplasms presenting in
      the blood and bone marrow, fine needle aspirates, and body fluids as well as
      cultured cells. In addition, this versatile method may facilitate the exploration
      of gene expression profiling and protein expression in clinical trials where
      regular tissue biopsies are not available.

PMID- 20690057
TI  - Tissue microarrays from biopsy specimens.
AB  - The construction of tissue microarrays from needle core biopsy specimens allows
      for the study of diseases with limited tissue samples and provides insight into
      tumors that are treated with nonsurgical approaches. While the techniques are
      technically challenging, in the hands of investigators they can reveal new
      insights into biomarkers of disease.

PMID- 20690058
TI  - Immunohistochemical analysis of tissue microarrays.
AB  - Immunohistochemistry (IHC) is the gold standard methodology for in-situ protein
      expression analysis in tissue samples. The combination of IHC and tissue
      microarray (TMA) technology allows for the simultaneous analysis of hundreds of
      tissue samples with an unprecedented degree of experimental standardization. The
      same immunostaining protocols used for conventional large sections can be used
      for TMAs, including antigen retrieval procedures for staining of routinely
      archived formalin-fixed tissue samples. The development of optimal IHC protocols
      is highly important for TMA studies because minor protocol variations often have
      a marked impact on the outcome of the staining. Preabsorption and isotype
      specific control experiments should be included as the last step in protocol
      development to proof target protein-specific binding. Such controls are
      particularly important for new antibodies with unknown staining patterns.

PMID- 20690059
TI  - DNA copy number analysis on tissue microarrays.
AB  - Detection of DNA sequence copy number changes is essential in both clinical
      practice and basic research, especially in cancer research. The combination of
      fluorescence in situ hybridization (FISH) and tissue microarray (TMA) technology
      provides high-throughput means for the evaluation of genetic aberrations in a
      large number of tissue samples. FISH on TMA is technically demanding and several
      protocols that include a variety of tissue pretreatment steps have been developed
      to improve the success of this methodology. Despite of the technical
      difficulties, FISH analysis on TMA has been successfully used not only to uncover
      genetic alterations in various malignancies but to also rapidly establish the
      clinical significance of such changes.

PMID- 20690060
TI  - RNA expression analysis on formalin-fixed paraffin-embedded tissues in TMA format
      by RNA in situ hybridization.
AB  - The technique of RNA in situ hybridization, i.e., the detection of specific
      messenger RNA sequences within structurally intact cells or tissues is not widely
      used in biomedical research, because it can be cumbersome and technically
      challenging. However, it has a major advantage that warrants and sometimes even
      requires its application and the associated efforts. RNA in situ hybridization
      enables a detailed analysis of gene expression in the absence of a suitable
      antibody to the molecule encoded by the gene of interest. Within the wealth of
      RNA analysis technologies available nowadays, RNA in situ hybridization still is
      the only methodology that allows a precise localization of gene expression at a
      cellular level. This is particularly important if, e.g., new molecular markers or
      potential drug target molecules have to be analyzed in large cohorts of human
      tissues. In cancer research, it may be necessary to show that a newly
      characterized molecule is indeed expressed by the tumor cells themselves, rather
      than by any surrounding tissue. A protocol is presented here that has been
      routinely and successfully used on FFPE tissues assembled on a tissue micro array
      (TMA).

PMID- 20690061
TI  - Automated analysis of tissue microarrays.
AB  - The analysis of protein expression in tissue by immunohistochemistry (IHC)
      presents three significant challenges. They are (1) the time-consuming nature of
      pathologist-based scoring of slides; (2) the need for objective quantification
      and localization of protein expression; and (3) the need for a highly
      reproducible measurement to limit intra- and inter-observer variability. While
      there are a variety of commercially available platforms for automated chromagen
      based and fluorescence-based image acquisition of tissue microarrays, this
      chapter is focused on the analysis of fluorescent images by AQUA(R) analysis
      (Automated QUantitative Analysis) and the solutions offered by such a method for
      research and diagnostics. AQUA analysis is a method for molecularly defining
      regions of interest or "compartments" within a tissue section. The methodology
      can be utilized with tissue microarrays to provide rapid, quantitative,
      localized, and reproducible protein expression data that can then be used to
      identify statistically relevant correlations in populations. Ultimately this
      allows for a multiplexed, objective and standardized quantitative approach for
      biomarker research and diagnostic assay development for protein expression in
      tissue.

PMID- 20690062
TI  - Digital microscopy for boosting database integration and analysis in TMA studies.
AB  - The enormous amount of clinical, pathological, and staining data to be linked,
      analyzed, and correlated in a tissue microarray (TMA) project makes digital
      slides ideal to be integrated into TMA database systems. With the help of a
      computer and dedicated software tools, digital slides offer dynamic access to
      microscopic information at any magnification with easy navigation, annotation,
      measurement, and archiving features. Advanced slide scanners work both in
      transmitted light and fluorescent modes to support biomarker testing with
      immunohistochemistry, immunofluorescence or fluorescence in situ hybridization
      (FISH). Currently, computer-driven integrated systems are available for creating
      TMAs, digitalizing TMA slides, linking sample and staining data, and analyzing
      their results. Digital signals permit image segmentation along color, intensity,
      and size for automated object quantification where digital slides offer superior
      imaging features and batch processing. In this chapter, the workflow and the
      advantages of digital TMA projects are demonstrated through the project-based
      MIRAX system developed by 3DHISTECH and supported by Zeiss.The enhanced features
      of digital slides compared with those of still images can boost integration and
      intelligence in TMA database management systems, offering essential support for
      high-throughput biomarker testing, for example, in tumor progression/prognosis,
      drug discovery, and target therapy research.

PMID- 20690063
TI  - From gene to clinic: TMA-based clinical validation of molecular markers in
      prostate cancer.
AB  - Current high-throughput screening techniques using DNA arrays have identified
      hundreds of new candidate biomarkers for diagnosis and risk prediction of
      prostate cancer. Large-scale analysis of clinical prostate cancer specimens is a
      key prerequisite for the validation of these genes. We have constructed a tissue
      microarray from more than 2,500 prostate cancers with full histo-pathological and
      clinical long-term follow-up data and analyzed expression and gene copy number
      patterns of 16 different candidate markers for their ability to predict prostate
      cancer progression and patient prognosis. The best candidates were used to extend
      established clinical prediction tools (nomograms) that were based on nonmolecular
      data only, such as prostate-specific antigene (PSA), clinical stage, and
      histological grading (Gleason grade). Using this approach, we could identify
      ANXA3 as an independent marker, which was capable of increasing the accuracy of
      the clinical nomogram, thereby fulfilling the criteria of a novel prognostic
      prostate cancer marker. This approach of integrating large-scale clinical and
      molecular variables may provide a new paradigm for the use of molecular profiling
      to predict the clinical outcome in prostate cancer.

PMID- 20690069
TI  - The (TAAAA)n polymorphism of the SHBG gene in men with the metabolic syndrome.
AB  - OBJECTIVE: Low serum Sex Hormone-Binding Globulin (SHBG) has been proposed as an
      indicator of the Metabolic Syndrome (MS) and cardiovascular disease in men. On
      the other hand, the (TAAAA)n repeat polymorphism in the SHBG gene has been shown
      to affect SHBG levels. The possible role of this polymorphism in the MS was
      examined in the present study. DESIGN: The study population consisted of 83 men
      with MS aged 54.9+/-14.8 years and 166 healthy men of the same age. The diagnosis
      of MS was based on the criteria proposed by the National Cholesterol Education
      Program - Third Adult Treatment Panel (NCEP-ATP III). The waist circumference was
      recorded and blood samples were obtained after overnight fasting for biochemical
      and hormonal tests. The SHBG(TAAAA)N polymorphism was genotyped in peripheral
      blood leucocytes. RESULTS: Genotype analysis for the (TAAAA)n polymorphism of the
      SHBG gene in the patients and controls identified 6 alleles having 6-11 TAAAA
      repeats. Patients with MS had more frequently short-allele genotypes (with 6/6,
      6/7, 6/8, 7/7, 7/8 or 8/8 tandem repeats) compared to controls (53% vs. 39.8%,
      p=0.047). In the entire study population, men homozygous for the 6 TAAAA repeat
      allele had lower SHBG levels (p=0.01) and higher waist circumference (p=0.006)
      than men heterozygous or non-carriers of this allele. CONCLUSION: Short
      SHBG(TAAAA)N allele genotypes may play a role in the development of the MS. The
      mechanism of this contribution remains unclear.

PMID- 20690070
TI  - A prospective study on the use of the indicator test Neuropad(r) for the early
      diagnosis of peripheral neuropathy in type 2 diabetes.
AB  - AIM: The aim of this prospective study was to evaluate the contribution of the
      indicator test for sudomotor function Neuropad(r) to the early diagnosis of
      peripheral neuropathy in patients with type 2 diabetes mellitus. Included were
      109 type 2 diabetic patients (55 men, mean age 56.15 +/- 6.14 years), whose
      initial clinical examination (Neuropathy Disability Score, NDS) was negative for
      neuropathy. Patients were first examined between January and June 2004 and re
      examined 5 years later by the NDS and Neuropad (r). Initially, 70 patients
      (64.22%) had normal and 39 (35.78%) patients had abnormal Neuropad(r) (groups A
      and B, respectively). NDS was significantly higher in group B on both
      examinations (p < 0.001). On the second examination, 2 patients (2.86%) in group
      A and 10 patients (25.64%) in group B had developed neuropathy (p = 0.001).
      Neuropad(r) had 83.33% sensitivity and 68.04% specificity for neuropathy. There
      was a modest but significant agreement (kappa = 0.259, p < 0.001) between
      Neuropad(r) and NDS for neuropathy. CONCLUSIONS: Among type 2 diabetic patients
      with normal NDS, development of neuropathy is significantly more frequent in
      those with abnormal Neuropad(r). These results suggest a potential utility of
      Neuropad(r) for the earlier diagnosis of neuropathy in type 2 diabetes.

PMID- 20690071
TI  - Effects of exercise on the levels of peptide YY and ghrelin.
AB  - Ghrelin and peptide YY (PYY) are brain-gut peptides that have a variety of
      physiological functions and are involved in energy regulation. Thus far,
      abnormalities in the expression and secretion of ghrelin and PYY are known to
      occur in lifestyle-related diseases, including obesity, and the improvement of
      these abnormalities has become an important challenge. Exercise has recently been
      reported to influence ghrelin and PYY concentrations. Exercise increases the PYY
      secretion. The effects of exercise on ghrelin levels vary with the study subject,
      timing of exercise, and duration of exercise. Here, we review the findings of
      recent studies on the association of PYY and ghrelin with obesity, particularly,
      on the influence of exercise on PYY and ghrelin levels.

PMID- 20690072
TI  - Long-term but not short-term aspirin treatment attenuates diabetes-associated
      learning and memory decline in mice.
AB  - Increasing studies have shown that the patients with diabetes mellitus have an
      increased risk of cognitive impairment, dementia, and neurodegeneration. The
      present study was designed to evaluate the effect of aspirin on diabetes
      associated learning and memory decline in mice. Diabetes was induced by a single
      intraperitoneal injection of streptozocin (150 mg/kg body weight) in C57BL/6
      mice. The mice were administered with aspirin at a dose of 30 mg/kg by
      intragastric administration once a day for 1, 4 or 8 weeks respectively. 8 weeks
      after aspirin or vehicle treatment, the effect of aspirin on diabetes-associated
      learning and memory decline in mice was investigated by evaluating the mean
      escape latency and the percentage of time spent in target quadrant. The TNF
      alpha, IL-1beta contents, and acetylcholinesterase activity in hippocampus were
      assayed as well. The results showed that administration with aspirin for 4 weeks
      or 8 weeks significantly reduced the mean escape latency, the
      acetylcholinesterase activity, the TNF-alpha, IL-1beta levels and increased the
      percentage of time spent in target quadrant. However, treatment with aspirin for
      1 week did not ameliorate diabetes-associated learning and memory decline. The
      present study demonstrated that long-term aspirin treatment attenuates diabetes
      associated learning and memory decline in mice, and that the effect of aspirin
      was related to its anti-inflammatory potency.

PMID- 20690073
TI  - Is hypoandrogenemia a component of metabolic syndrome in males?
AB  - OBJECTIVES: This study was done to assess testosterone deficiency in males with
      metabolic syndrome (MetS) and the effect of testosterone replacement on insulin
      resistance and biochemical parameters of this syndrome with hypogonadism. Sixty
      three males fulfilling the International Diabetes Federation 2005 MetS guidelines
      as cases and 32 healthy males as controls with the mean age of 35.29+/-8.16 and
      34+/-6.76 years respectively were enrolled in the study. Fasting blood samples
      were collected for gonadal profile and insulin assay. Homeostasis model
      assessment for insulin resistance (HOMA-IR) and free testosterone index were
      calculated. Hypogonadism was defined when the calculated free testosterone value
      was <0.225 nmol/L. FINDINGS: Total and calculated free testosterone, sex hormone
      binding globulin (SHBG) were lower in cases than controls (P<0.001). Hypogonadism
      was seen in 19 (30%) cases with MetS while 1 (3.1%) in controls. MetS cases with
      hypogonadism had significantly higher HOMA-IR than eugonadal cases.
      Hypogonadotropic hypogonadism was observed in 16 (84%) cases. Treatment with oral
      Testosterone 40 mg twice a day for 3 months led to significant improvement of
      HOMA-IR (P<=0.001) in the MetS males with hypogonadism. CONCLUSIONS: This study
      revealed that males with MetS with or without diabetes had lower serum
      testosterone than their age matched healthy subjects. Hypogonadism was also
      common in subjects with MetS. Testosterone therapy to correct hypoandrogenimia
      improved insulin sensitivity and other biochemical parameters except High density
      lipoprotein cholesterol in MetS. This emphasizes that hypogonadism in all men
      with MetS or MetS in all men with hypogonadism needs clinical evaluation and
      subsequent management.

PMID- 20690074
TI  - Neuro-endocrine and neuropsychological outcome after aneurysmal subarachnoid
      hemorrhage (aSAH): a prospective cohort study.
AB  - OBJECTIVE: Neuropsychological sequelae are common after aneurysmal subarachnoid
      hemorrhage (aSAH) and may be associated with or caused by supposed hypothalamic
      pituitary dysfunction. We evaluated the incidence of neuro-endocrine and
      neuropsychological deficits after aSAH and their interrelations in a standardized
      manner. METHODS: 26 patients (20 females) were prospectively screened for neuro
      endocrine and neuropsychological deficits 3 and 6 months after aSAH. We measured
      GH, IGF-1, prolactin, LH, FSH, estradiol, TSH, fT4, total T3, testosterone, ACTH
      as well as cortisol before and after ACTH-stimulation. Neuropsychological
      analysis covered verbal comprehension, short term and working memory,
      visuospatial construction, figural memory, psychomotor speed, attention, and
      concentration. RESULTS: After 3 months central hypogonadism was observed in 2
      patients accompanied by central hypothyroidism in 1 male subject. Central
      hypogonadism resolved spontaneously after 6 months in both. After 3 months,
      neuropsychological deficits were detected in 57% of the examined patients (44%
      attention deficits, 38% memory impairment, 12% psychomotor deficits).
      Neuropsychological deficits were still present in 53% after 6 months. CONCLUSION:
      We found a low prevalence of neuro-endocrine and a high prevalence of
      neuropsychological deficits in patients 3 and 6 months after aSAH. Thus, the
      absent co-incidence of central hormonal and psychological dysfunction leaves a
      causal association questionable.

PMID- 20690075
TI  - Monitoring medical treatment in adolescents and young adults with congenital
      adrenal hyperplasia: utility of salivary 17alpha-hydroxyprogesterone day
      profiles.
AB  - INTRODUCTION: Efficacy of medical treatment in patients with 21-hydroxylase
      deficiency is usually monitored by measurement of 17alpha-hydroxyprogesterone
      (17OHP). Saliva instead of serum sampling offers some advantages, such as
      painless handling and measurement of the bioactive free hormone. This study
      evaluated the diagnostic validity of salivary 17OHP for monitoring medical
      treatment, with samples collected at 7 time points throughout a day. SUBJECTS AND
      METHODS: Day profiles were performed in 23 adolescents and young adults with 21
      hydroxylase deficiency and 43 healthy volunteers. During each profile, saliva and
      serum samples for 17OHP were simultaneously collected. RESULTS: With regard to
      the initial day profiles, samples were pathological in 63% (saliva) and 41%
      (serum). After the first day profile 14 patients underwent adjustment of medical
      treatment, either because of highly elevated 17OHP levels or with the aim of dose
      reduction. When comparing the best with the first day profile fewer samples were
      pathological (saliva: 32% vs. 71%; p<0.05; serum: 21% vs. 47%; n. s.), while the
      mean hydrocortisone equivalent dose was significantly reduced (20.09 mg vs. 27.27
      mg; p<0.01). In 53% of profiles with controlled salivary 17OHP levels at 0700 h,
      the necessity for a treatment modification became only apparent when analyzing
      the whole day profile. CONCLUSION: A single 0700 h value within the reference
      range does not allow for a reliable assessment of therapeutic efficacy. We
      therefore suggest 17OHP day profiles for monitoring medical treatment. In this
      context, saliva analysis appears to be more sensitive in identifying patients who
      are inadequately treated.

PMID- 20690076
TI  - Maturity-Onset Diabetes of the Young (MODY) caused by a novel nonsense mutation
      E41X in the HNF-1alpha gene.
AB  - The most common cause of Maturity-Onset Diabetes of the Young (MODY) are
      mutations in the Hepatic Nuclear Factor 1alpha (HNF-1alpha) gene, resulting in
      MODY3. In a family afflicted with diabetes, a novel nonsense mutation in HNF
      1alpha, E41X, causing a termination codon behind the dimerization domain, was
      found. The penetrance in individuals older than 25 years was 81.8%. The age at
      manifestation of diabetes ranged from 18 to 63 years, only 2 out of 10 diabetic
      individuals developed the disease at ages younger than 25 years. Although
      diabetes duration lasted up to 35 years in this family, only one family member
      suffered from diabetic complications. Additional polymorphisms in HNF-1alpha,
      I27L and S487N, were found in this pedigree. Despite its biological inactivity,
      S487N polymorphism led in combination with E41X to a significant earlier
      manifestation of diabetes, whereas I27L polymorphism or increased Body Mass Index
      (BMI) did not. In spite of the severe gene defect, which truncates the protein
      behind the dimerization domain, the phenotype of E41X was relatively benign
      without frequent diabetic complications.

PMID- 20690077
TI  - Does the right inferior phrenic artery have a supplying role in liver cirrhosis
      without hepatocellular carcinoma? A 64-slice CT study.
AB  - PURPOSE: To investigate whether the right inferior phrenic artery (RIPA) has a
      role in supplying the liver in cirrhotic patients without hepatocellular
      carcinoma (HCC) using 64-slice computed tomography (CT). MATERIALS AND METHODS:
      Fifty-eight consecutive cirrhotic patients were categorized into two groups in
      regard to the absence (group 1, n=33) or presence of portal vein thrombosis
      (group 2, n=25). In addition, 35 patients without liver disease were included as
      a control group (group 0). The diameters of the RIPA and left inferior phrenic
      artery (LIPA) were measured in the ascending portion of these vessels using
      arterial-phase CT images. The discrepancy between the diameters of the RIPA and
      LIPA were calculated. The diameters of the RIPA and LIPA and the discrepancy
      between the diameters of the RIPA and LIPA were then compared. RESULTS: The
      characteristics of all RIPA and LIPA were visualized. The diameter of the LIPA
      among the three groups was not significantly different (P = 0.363). The mean
      diameters of the LIPA were 1.8+/-0.19, 1.8+/-0.22, and 1.7+/-0.38 mm for groups
      0, 1, and 2, respectively. The diameter of the RIPA was significantly greater
      (2.1+/-0.54 mm) in groups 1 and 2 (1.9+/-0.19 mm) than in group 0 (1.8+/-0.18
      mm). There was significantly difference between groups 0 and 2 (P = 0.003), and
      groups 1 and 2 (P = 0.01) with regard to the discrepancy of the diameters of RIPA
      and LIPA. CONCLUSION: The RIPA may contribute to the blood supply of the liver in
      cirrhotic patients, especially those with portal venous thrombosis.

PMID- 20690078
TI  - CT angiography of the celiac trunk: anatomy, variants and pathologic findings.
AB  - Celiac trunk variants and pathologies are relatively common occurrences. With the
      advent of computed tomography (CT) technology, these conditions are being
      diagnosed with an increased frequency even among asymptomatic patients. CT
      angiography is used noninvasively for preoperative staging and vascular mapping
      in patients with pancreatic and hepatobiliary neoplasm. Multidetector-row CT
      (MDCT) also allows the accurate depiction of the abdominal splanchnic vessels for
      stenosis, collateral vessels and atherosclerotic plaques. In this study, we
      describe the normal anatomy and variants of the celiac trunk as well as
      associated pathologic conditions, such as stenosis, occlusion, aneurysm and
      median arcuate ligament compression syndrome. The overall aim of this study was
      to emphasize the clinical importance of these abnormalities.

PMID- 20690079
TI  - Effects of percutaneous transhepatic biliary drainage on renal function in
      patients with obstructive jaundice.
AB  - PURPOSE: We assessed the effects of percutaneous transhepatic biliary drainage on
      renal function in patients with obstructive jaundice using the estimated
      glomerular filtration rate (eGFR) and evaluated the factors associated with renal
      dysfunction. MATERIALS AND METHODS: Between July 2007 and September 2009, 108
      consecutive patients (69 men 39 women; median age, 59 years; range, 29-87 years)
      with obstructive jaundice (20 benign, 88 malignant) that were unsuitable for
      endoscopic retrograde cholangiopancreticography were evaluated at admission and
      at follow-up exams five and thirty days after percutaneous transhepatic biliary
      drainage. Two patients with suspected contrast-induced nephropathy were excluded.
      Renal function was assessed by measuring levels of urea, creatinine and
      electrolytes and evaluating the modification of diet in the renal disease formula
      for eGFR. RESULTS: eGFR was < 60 mL/min/1.73 m2 before percutaneous transhepatic
      biliary drainage in 27 patients (25%) and increased significantly 30 days after
      percutaneous transhepatic biliary drainage (P = 0.008). In the malignant external
      drainage subgroup, there was a significant increase in eGFR on the fifth day
      after percutaneous transhepatic biliary drainage (P = 0.038). The procedure
      related mortality rate was zero. Nine malignant patients (8.49%) died within
      thirty days due to underlying diseases. On the fifth day, eGFR was significantly
      lower in these patients than in surviving patients (P = 0.049), and bilirubin
      levels were significantly higher before the intervention than in surviving
      patients (P = 0.04). Multiple logistic regression analysis showed that serum
      direct bilirubin is a significant predictor of renal function (P = 0.049).
      CONCLUSION: Obstructive jaundice is associated with renal dysfunction, and serum
      direct bilirubin is a significant predictor of renal function. Percutaneous
      transhepatic biliary drainage improves renal function and is crucial for
      prognosis of obstructive jaundice.

PMID- 20690080
TI  - Citrullinemia type I: molecular screening of the ASS1 gene by exonic sequencing
      and targeted mutation analysis.
AB  - We developed a mutation-screening protocol for the ASS1 gene in order to guide
      clinical management of neonates with elevated citrulline detected during routine
      newborn screening. An exon-based amplification and sequencing method was designed
      and successfully applied to patients to identify disease-associated mutations.
      The sequencing-based method was applied to three patients with mild or
      asymptomatic clinical courses. Identification of a homozygous mutation in these
      patients, c.787G>A (p.Val263Met), led to the development of a tetra-primer ARMS
      PCR method that successfully detected the mutation in DNA extracted from blood or
      from Guthrie card spots.

PMID- 20690081
TI  - Genome-wide analysis of cyclins in maize (Zea mays).
AB  - Cyclins are primary regulators of the activity of cyclin-dependent kinases and
      play crucial roles in cell cycle progression in eukaryotes. Although extensive
      studies have revealed the roles of some cyclins and underlying mechanisms in
      plants, relatively few cyclins have been functionally analyzed in maize. We
      identified 59 cyclins in the maize genome, distributed on 10 chromosomes; these
      were grouped into six types by phylogenetic analysis. The cyclin genes in the
      maize genome went through numerous tandem gene duplications on five chromosomes.
      However, no segmental duplications, which occur in rice, were found on maize
      chromosomes. This information allows us to assess the position of plant cyclin
      genes in terms of evolution and classification, which will be useful for
      functional studies of maize cyclins.

PMID- 20690082
TI  - Genetic variability among natural populations of Zaprionus indianus
      (Drosophilidae) in the States of Sao Paulo and Minas Gerais, Brazil.
AB  - Random amplified polymorphic DNA (RAPD) was used to detect polymorphisms among
      Zaprionus indianus fly populations collected from six municipalities in the
      States of Sao Paulo and Minas Gerais, Brazil. This species is an important,
      recently introduced fruit fly pest of figs and other fruit. Among 21 primers, 16
      produced 73 reproducible polymorphic fragments; primer AM-9 produced the greatest
      number of polymorphic bands (nine), with 52% genetic variability among
      populations. Genetic divergence analysis of the Z. indianus populations
      demonstrated two major groups, named Western and Eastern groups. There was
      greater gene flow within than between groups. The correlation coefficient for
      genetic and geographic distances (Mantel test) was significant, demonstrating
      isolation by distance.

PMID- 20690083
TI  - Development of microsatellite markers for Hoplias malabaricus (Erythrinidae).
AB  - We identified 14 microsatellite loci for the wolf fish, Hoplias malabaricus
      (Erythrinidae), from a genomic shotgun library. Twenty-five primers were
      designed, and 48 individuals of H. malabaricus from four localities of northwest
      Goias, in central Brazil, were genotyped to characterize the polymorphism at each
      locus. Fourteen primers amplified clearly interpretable products using a single
      PCR protocol; six loci were polymorphic, but with a low number of alleles per
      locus (2 or 3). Expected heterozygosities for polymorphic loci ranged from 0.136
      to 0.505. Combined paternity exclusion probability (0.638) was low and combined
      genetic identity (0.056) was high in studies of parentage. The low polymorphism
      may be due to the small microsatellite size and the large size of the motifs.

PMID- 20690084
TI  - No association of polymorphisms in the suppressor of cytokine signaling (SOCS)-3
      with rheumatoid arthritis in the Chinese Han population.
AB  - Suppressor of cytokine signaling (SOCS)-3 is a key negative regulator of cytokine
      signaling that inhibits the JAK/STAT signal transduction pathway; there are
      reports describing its role in attenuating arthritis through SOCS-3
      overexpression. We examined the relationship between polymorphisms in the coding
      sequence and promoter region of SOCS-3 and rheumatoid arthritis (RA) in a Chinese
      Han population. Two single-nucleotide polymorphisms in the SOCS-3 5' region: 
      1044 C>A within the promoter region and rs12953258 (-920 C>A) in the 5'UTR (exon
      2) of SOCS-3 were studied by restriction fragment length polymorphism analysis
      and tetra-ARMS-PCR in 100 RA patients and 100 healthy adults. The prevalence of
      the homozygous genotype -1044 CC was 100% in both RA and control groups. The
      heterozygous genotype (-920 C>A) was present in 89% of RA and in 82% of the
      control group, which is significantly different from the distribution in Western
      people. There was no transmission disequilibrium between these two SNPs (r(2) =
      0.000). We did not detect significant differences in allele or genotype
      frequencies for either of these SNPs between the RA group and controls (P >
      0.05). There was no association between rheumatoid factor and SOCS-3 SNP
      rs12953258 (P = 0.258). We conclude that SOCS-3 polymorphism is not a genetic
      risk factor for RA in Chinese patients.

PMID- 20690085
TI  - Worldwide diversity of the Y-chromosome tetra-local microsatellite DYS464.
AB  - Of all DNA markers on the human Y-chromosome, the tetra-local Y-linked
      microsatellite DYS464 is the most polymorphic. We genotyped DYS464 in 677 male
      samples collected worldwide, maintained in the HGDP-CEPH Human Genome Diversity
      Cell Line Panel. Fourteen different alleles were found, with allele lengths
      varying from 9 to 23 repeats. One hundred and seventy-five different genotypes
      were detected, of which 90 appeared to be continent-specific. The region with the
      highest percentage of unique genotypes was Africa. Genotype diversity was 0.98
      for Europe, 0.97 for Central and East Asia, 0.95 for Africa, 0.94 for Oceania,
      0.92 for the Middle East, and 0.90 for the Americas. A hierarchical analysis of
      molecular variance showed low levels of worldwide genetic structure; 88.42% of
      the genetic variance was found within populations, 9.62% between populations
      within regions and 1.96% between regions. Since the four DYS464 repeats are
      identical, one cannot assign each peak in the electropherogram to a specific
      locus. Thus, the same genotype may correspond to several haplotypes, with
      different permutations of alleles. Consequently, genotypes are degenerate, which
      limits phylogeographical analyses. Yet, because of its high variability, DYS464
      still constitutes an informative tool for population and evolutionary studies.

PMID- 20690086
TI  - Images beyond clinical presentation? Promising, but not confirmed in ESRD
      transplant candidates.

PMID- 20690087
TI  - Clinical implication of gastrointestinal bleeding in degenerative aortic
      stenosis: an update.
AB  - Gastrointestinal (GI) bleeding due to colonic angiodysplasias can be associated
      with calcifying aortic stenosis (AS). GI angiodysplasias and AS are defined as
      chronic degenerative disorders, and the prevalence of both diseases increases
      with age. Moreover, degenerative AS is associated with increased destruction of
      high molecular weight multimers of von Willebrand factor which can promote
      bleeding from intestinal angiodysplasias. The coincidence of gastrointestinal
      bleeding angiodysplasias and AS has been known for many years as Heyde's
      syndrome. Aortic valve replacement is the first line therapy for advanced stage
      AS-patients, but can also be an effective treatment for co-existent bleeding
      angiodysplasias and acquired von Willebrand disease. In this study, we tried to
      collect as well as systemized data about the etiopathogenesis of AS coagulation
      abnormalities and diagnostic, clinical and therapeutic implications of AS-patient
      with GI angiodysplasias.

PMID- 20690088
TI  - Safety of pharmacotherapy of osteoporosis in cardiology patients.
AB  - The commonest medical conditions following menopause are osteoporosis and
      atherosclerotic disease. This review considers the safety of pharmacotherapy of
      osteoporosis in cardiology patients. Drugs used for osteoporosis treatment may
      have adverse effects on the cardiovascular system. This article has detailed
      analysed of current drug classes, such as the bisphosphonates and strontium
      ranelate, as well as reviewed of the controversy surrounding hormone replacement
      therapy (HRT) and the selective estrogen receptor modulators (SERMs).
      Additionally, we discuss the adverse effects on the heart of calcium and drugs
      influencing calcium metabolism such as vitamin D, parathormone and calcitonin. We
      look at the interference between osteoporosis treatment and the drugs used for
      atherosclerosis. Moreover, the side effects on bones of cardiology drugs are
      analysed. Lastly, the possible advantages of selected drugs used for
      cardiovascular diseases in terms of osteoporosis prevention are evaluated.

PMID- 20690089
TI  - Predictors of early graft patency following coronary artery bypass surgery.
AB  - BACKGROUND: The long-term success of coronary artery bypass graft surgery (CABG)
      is dependent on graft patency after the operation. Early occlusion (within the
      first week) affects the long-term results. Therefore, we sought to determine pre
      operative, intraoperative, and perioperative factors associated with early
      coronary graft patency. METHODS: Between March 2007 and March 2008, 107
      consecutive patients (81 men, 26 women, mean age 60 +/- 9 years) who underwent
      CABG were included in this study. The enrolled patients underwent 16-slice
      computed tomography angiography one week after CABG. RESULTS: Based on the
      multislice computed tomography, acute graft occlusion was detected in 32 (8.7% of
      all) grafts, including 26 of 250 (10%) in venous grafts and 6 of 116 (5%) in
      arterial grafts. In univariate analysis, patients with patent coronary grafts had
      a lower serum glucose level (119 +/- 30 vs. 141 +/- 65 mg/dL, p = 0.02) and
      longer partial thromboplastin time (34 +/- 11 vs. 30 +/- 2 s, p = = 0.04). In
      addition, pump time was significantly longer in patients with occluded grafts
      than in those with patent grafts (119 +/- 43 vs. 102 +/- 32 min, p = 0.04). Those
      with longer pump time required more coronary grafts (pump time > or = 120 min for
      3.5 grafts vs. pump time < 120 min for 2.9 grafts, p = 0.02). Of the multiple pre
      operative, intraoperative, and perioperative characteristics of the patients who
      underwent successful CABG, serum glucose level (OR: 2.014, 95% CI: 1.002-3.026, p
      = 0.002) and pump time < two hours (OR: 1.502, 95% CI: 1.001-2.030, p = 0.003)
      were the only predictors of coronary graft patency seven days after surgery in
      multivariate analysis. CONCLUSIONS: Our study demonstrated that the patients with
      successful CABG and patent coronary grafts within the first week after surgery
      had optimal blood glucose control and pump time < two hours.

PMID- 20690090
TI  - Coronary computed tomography angiography in dialysis patients undergoing pre
      renal transplantation cardiac risk stratification.
AB  - BACKGROUND: This study addresses the safety, feasibility, and interpretability of
      coronary computed tomography angiography (CCTA) in excluding significant coronary
      artery disease in end-stage renal disease patients on dialysis undergoing pre
      renal transplant cardiac risk evaluation. METHODS: Twenty nine patients (55.5 +/-
      10.2 years) undergoing cardiac risk assessment prior to renal transplantation,
      underwent research CCTA with calcium scoring and formed the study group. All
      CCTAs were performed using retrospective acquisition, with beta-blockade provided
      one hour prior to scanning. RESULTS: No major complications occurred in this
      group up to 30 days after CCTA. Of the total of 374 segments interpreted by both
      readers, only 36 (10%) were uninterpretable by both readers. Of these, 31 (86%)
      were from distal segments or branches. On a segmental level, there was 95%
      concordance between both readers for < 50% stenosis detection. Only three out of
      28 (11%) CCTAs were deemed uninterpretable. Ten patients (36%) had zero calcium
      score, despite being on dialysis with no evidence of obstructive coronary artery
      disease by CCTA. CONCLUSIONS: CCTA is feasible and safe in end-stage renal
      disease dialysis patients with the advent of 64-slice CCTA. Despite significant
      calcium burden, there was excellent inter-observer agreement at segment level for
      the left main and all three proximal-mid coronary arteries in excluding
      obstructive coronary artery disease (> 50% stenosis).

PMID- 20690091
TI  - Oxygen uptake efficiency slope correlates with brain natriuretic peptide in
      patients with heart failure.
AB  - BACKGROUND: Cardiopulmonary exercise testing is a well-established tool for
      clinical and prognostic assessment of patients with chronic heart failure (CHF).
      Recently, a new parameter of this examination--oxygen uptake efficiency slope
      (OUES)--has been described and proposed as a new prognostic factor in patients
      with CHF. Brain natriuretic peptide (BNP) is an established prognostic factor in
      CHF. The purpose of the study was to assess OUES in patients with CHF in relation
      to other cardiopulmonary parameters and BNP levels. METHODS: The study group
      consisted of 42 patients with CHF and left ventricular ejection fraction (LVEF) <
      45% (mean age 50.2 +/- 9.3 years, mean ejection fraction 26.1 +/- 8.1% and NYHA
      functional class - 2.5 +/- 0.8) and eight healthy controls (age 43.6 +/- 14.7
      years). Coronary artery disease was diagnosed in 16 patients (38%). All underwent
      maximal cardiopulmonary exercise treadmill test. BNP level was measured using
      Abbott AxSYM Immunoassay system. RESULTS: There were significant (p < 0.001)
      differences between the patients and controls in BNP levels (350 +/- 520 vs 14 +/
      19 pg/mL), OUES (1.7 +/- 0.4 vs 2.7 +/- 0.5), peak VO(2) (17.1 +/- +/- 5.1 vs
      36.9 +/- 4.9 mL/kg/min), O(2) pulse (10.9 +/- 3.3 vs 15.9 +/- 2.7) and VE/VCO(2)
      slope (35.7 +/- 7.8 vs 25.7 +/- 2.7). In patients, OUES was significantly (p <
      0.001) correlated with LVEF (r = 0.54), BNP levels (r = -0.49), peak VO(2) (r =
      0.80), VO(2) AT (r = 0.65) and VE/VCO(2) slope (r = -0.59). BNP was independently
      related to OUES in multivariate regression analysis. CONCLUSIONS: Oxygen uptake
      efficiency slope is significantly reduced in patients with CHF and correlates
      with peak VO(2) and other parameters of cardiopulmonary exercise treadmill test.
      It is not related to age. BNP is an independent marker of OUES in patients with
      CHF.

PMID- 20690092
TI  - The modified Selvester QRS score: can we predict successful ST segment resolution
      in patients with myocardial infarction receiving fibrinolytic therapy?
AB  - BACKGROUND: We sought to explore whether the simplified Selvester QRS scoring
      system could predict ST segment resolution in patients with first acute ST
      segment elevation myocardial infarction who receive pharmacological reperfusion
      therapy. METHODS: We enrolled 60 consecutive patients admitted to the critical
      care unit with the diagnosis of first acute ST segment elevation myocardial
      infarction presenting within 24 hours from symptom onset, and eligible for
      reperfusion therapy. All patients received streptokinase in the usual dose
      regimen. Patients underwent resting high-quality 12-lead electrocardiogram
      recordings to calculate the modified QRS score and estimate the sum of ST segment
      elevation before (STE1) and 90 minutes after (STE2) streptokinase. The difference
      between STE1 and STE2 was then measured and accepted as the sum of ST segment
      resolution, expressed as SigmaSTR. Patients were classified into two groups:
      those with SigmaSTR > or = 50% of STE1 (the resolution group) and those with
      SigmaSTR < 50% (the non-resolution group). RESULTS: The mean QRS score was
      significantly lower in the resolution group compared to the non-resolution group
      (2.88 +/- 1.34 vs 5.93 +/- 1.56, respectively, p < 0.001). There was a highly
      significant negative correlation between QRS score and SSTR with a correlation
      coefficient r = -0.76. Using a cut-off value of > or = 4, the QRS score had a
      sensitivity of 93%, specificity of 72%, positive and negative predictive values
      of 74% and 92% respectively, for predicting SigmaSTR < 50%. CONCLUSIONS: The
      Selvester QRS score can reliably predict adequate ST segment resolution in
      patients with first acute ST segment elevation myocardial infarction receiving
      fibrinolytic therapy, with a high sensitivity and an acceptable specificity.

PMID- 20690093
TI  - Clinical utility of serum cystatin C in predicting coronary artery disease.
AB  - BACKGROUND: There is limited data regarding the clinical utility of cystatin C in
      patients with stable coronary artery disease (CAD). The aim of this study was to
      determine the predictive value of cystatin C for the presence and severity of CAD
      and the association between this protein and other biochemical risk factors for
      atherosclerosis in patients with suspected CAD. METHODS: Ninety-four patients
      with CAD, and 92 patients without CAD but with cardiovascular risk factors, were
      included in this study. Echocardiography and other pertinent laboratory
      examinations were performed. Subjects were divided into four groups according to
      their cystatin C quartile. Cystatin C groups were analyzed for the association
      with CAD characteristics. RESULTS: The number of patients with CAD increased as
      the quartile of cystatin C increased, and there was a remarkable difference
      between quartiles (p < 0.001). Logistic regression analysis revealed independent
      predictors of incident CAD as cystatin C, hs-CRP, eGFR, HDL cholesterol and SBP
      (p = 0.005, p = 0.027, p = 0.017, p = 0.014 and p = 0.001, respectively).
      Moreover, cystatin C concentration was significantly correlated with CAD severity
      score (b = 0.258, p < 0.01). A cut-off value of 0.82 mg/L for cystatin C
      predicted incident CAD with a sensitivity and specificity of 75.5% and 75.0%
      respectively. Cystatin C concentration also correlated well with the
      atherosclerotic biochemical risk factors like homocysteine, creatinine and hs
      CRP. CONCLUSIONS: Cystatin C could be a useful laboratory tool in predicting the
      presence and severity of CAD in daily practice. It also correlates significantly
      with biochemical risk factors for CAD, namely homocysteine, low HDL and CRP.

PMID- 20690094
TI  - The effect of early and intensive statin therapy on ventricular premature beat or
      non-sustained ventricular tachycardia in patients with acute coronary syndrome.
AB  - BACKGROUND: Our study's aim was to evaluate the prognostic value of early and
      intensive lipid-lowering treatment on ventricular premature beat or non-sustained
      ventricular tachycardia (NSVT) after acute coronary syndrome (STEMI, non-STEMI,
      and unstable angina pectoris). METHODS: Some 586 patients with acute coronary
      syndrome were randomly divided into two groups: Group A (with conventional statin
      therapy, to receive 10 mg/day atorvastatin, n = 289) and Group B (given early and
      intensive statin therapy, 60 mg immediately and 40 mg/day atorvastatin, n = 297).
      The frequency of ventricular premature beat and NSVT was recorded via Holter
      monitoring after hospitalization (24 h and 72 h). RESULTS: Seventy seven (11.8%)
      patients had NSVT. When compared to patients with no documented NSVT, patients
      with NSVT were older and more frequently had myocardial infarction in their
      history, diabetes mellitus, atrial fibrillation and an ejection fraction < 40%.
      Ventricular premature beats decreased significantly in the early and aggressive
      treatment group (24 h, p < 0.01; 72 h, p < 0.001). A significant reduction in
      NSVT was seen in the early and aggressive treatment group (24 h, p < 0.01; 72 h,
      p < 0.001). There were no side effects observed in either group. CONCLUSIONS:
      Early and intensive lipid-lowering treatment can clearly decrease ventricular
      premature beats and NSVT.

PMID- 20690095
TI  - Forward stroke volume is predictor of perioperative course in patients with
      mitral regurgitation undergoing mitral valve replacement.
AB  - BACKGROUND: Decreased left ventricle ejection fraction (LVEF) is a predictor of
      poor late outcome in patients with mitral regurgitation (MR). The relationship
      between pre-operative forward stroke volume (SV) and right heart parameters and
      perioperative outcome in patients with MR has been little studied. METHODS: Forty
      patients with severe organic MR, unsuitable for mitral valve repair, who
      underwent mitral valve replacement (MVR) were included in the study (50% men,
      average age 61 +/- 9 years). Exclusion criteria were: aortic valve disease,
      coronary artery disease, rethoracotomy, stroke, infection or significant
      perioperative bleeding. Pre-operative detailed echocardiographic examination was
      performed. The end-point was post-operative prolonged intensive care unit (ICU)
      stay of more than three days because of the need for inotropic support. RESULTS:
      Pre-operative NYHA class was 2.6 +/- 0.4, mean right ventricular end-diastolic
      diameter (RVEDD) was 28.7 +/- 4 mm, TAPSE was 20 +/- 4 mm, mean right ventricular
      systolic pressure (RVSP) was 38 +/- 13 mm Hg, left ventricular end-systolic
      diameter was 43.5 +/- 11 mm, left ventricular end-diastolic diameter was 60 +/-
      11 mm, left ventricular end-diastolic volume (Simpson) was 155 +/- 47 mL, LVEF
      was 55 +/- 11%, mean regurgitation fraction was 58% and forward SV (measured by
      Doppler) was 35 +/- +/- 11 mL. All patients survived the operation. Mean ICU stay
      was 3.2 +/- 2.9 days (range 1-10 days), mean TISS-28 was 623 +/- 293 and mean
      NEMS 151 +/- 85. By univariate analysis, ICU stay was significantly longer in
      patients in higher pre-operative NYHA (p = 0.04), lower LVEF (p = 0.01), lower
      forward SV (p = 0.001) higher RF (p = 0.01), pre-operative right ventricular
      dilatation (p = 0.04), higher RVSP (p = 0.006) and right ventricular dysfunction
      (p = 0.04). By multivariate analysis, forward SV (p = 0.002, b = -0.45) and RVEDD
      (p = 0.02, b = 0.31) were independent predictors for prolonged ICU stay.
      CONCLUSIONS: Pre-operative forward stroke volume and right ventricle size are
      predictors of the perioperative hemodynamic status in patients with mitral
      regurgitation undergoing MVR.

PMID- 20690096
TI  - Activation of the endogenous coagulation system in patients with atrial flutter:
      relationship to echocardiographic markers of thromboembolic risk.
AB  - BACKGROUND: Atrial thrombus formation in patients with atrial flutter raises
      concerns of stroke risk. We investigated patients with isthmus-dependent atrial
      flutter for coagulation abnormalities before and after cardioversion to sinus
      rhythm by catheter ablation, and evaluated the relationship of the abnormalities
      to the echocardiographic risk markers of stroke. METHODS AND RESULTS: Plasma
      samples were drawn prior to insertion of catheters, immediately after the
      procedure, and 24 hours afterwards. At baseline, coagulation abnormalities were
      found in 22 out of 25 patients (88%). von Willebrand factor antigen (vWF-Ag) and
      factor VIII:C were elevated in 17 patients (68%) and 15 patients (60%),
      respectively. At baseline, mean plasma levels of vWF-Ag (250.1 +/- 144.4%) and
      factor VIII:C (215.0 +/- 77.1%) were increased. Key markers of thrombin
      generation, thrombin-antithrombin III complex (TAT; 47.8 +/- 30.9 microg/L vs
      14.5 +/- 13.8 microg/L; p < 0.05) and prothrombin fragments 1.2 (F1.2; 2.5 +/-
      0.5 nmoL/L vs 1.2 +/- 1.0 nmoL/L) were significantly elevated in the presence of
      spontaneous echo contrast. Further, both markers of thrombin generation inversely
      correlated with left atrial appendage emptying velocity (r = -0.42 and -0.63, p <
      0.05). Levels of TAT and F1.2 increased after conversion and ablation.
      CONCLUSIONS: Endothelial-dependent coagulation factors were enhanced in most
      patients with atrial flutter. Spontaneous echo contrast and decreased atrial
      contractility were associated with increased thrombin generation. After
      conversion and ablation, an increase in thrombin generation and fibrinolysis
      suggest a transient pro-thrombotic state.

PMID- 20690097
TI  - Massive mitral regurgitation secondary to acute ischemic papillary muscle
      rupture: the role of echocardiography.
AB  - Papillary muscle rupture is an infrequent but often fatal mechanical complication
      of acute myocardial infarction (AMI). We report the case of an AMI complicated by
      the development of an abrupt cardiogenic shock due to the rupture of the head of
      the postero-medial papillary muscle with echocardiographic demonstration of
      severe mitral regurgitation due to flail posterior mitral valve leaflet. After
      initial stabilization with medical therapy and diagnostic coronary angiography,
      the patient was referred for urgent cardiac surgery and successfully underwent
      mitral valve replacement with implantation of a bioprosthesis. This case confirms
      the importance of transthoracic echocardiography in diagnosing mechanical acute
      complications during an AMI and in the decision making of patients with sudden
      onset of hemodynamic compromise. Transthoracic echocardiography should be
      immediately carried out in all patients in whom a mechanical complication during
      an AMI is suspected.

PMID- 20690098
TI  - Successful use of intra-aortic counter pulsation therapy for intractable
      ventricular arrhythmia in patient with severe left ventricular dysfunction and
      normal coronary arteries.
AB  - Intra-aortic balloon pumps (IABP) are commonly used in the setting of an acute
      myocardial infarction that is complicated by cardiogenic shock or mechanical
      complications such as a ventricular septal defect or papillary muscle rupture.
      IABP has also been shown to be useful in patients with refractory and
      hemodynamically unstable ventricular arrhythmias and refractory post-myocardial
      infarction angina. We report a case in which IABP was used in a patient with
      dilated cardiomyopathy and normal coronary arteries, who presented with
      persistent, recurrent and refractory ventricular tachycardia. His ventricular
      tachycardia settled immediately with the use of IABP therapy. He subsequently had
      an implantable defibrillator. The use of IABP is associated with favorable
      changes in the left ventricular wall tension and reduction in afterload, which
      could reduce the excitability of the myocardium, thus making it less prone to
      arrhythmias. The use of IABP is relatively safe and should be considered in
      patients with refractory ventricular arrhythmias, even if it is not associated
      with ischemia.

PMID- 20690099
TI  - Lithium intoxication causing ST segment elevation and wandering atrial rhythms in
      an elderly patient.
AB  - Lithium overdoses causing cardiotoxicity are uncommon and electrocardiographic
      changes suggesting myocardial ischemia are rare. However, some authors have
      specifically reported the occurrence of ischemic electrocardiography changes due
      to a lithium overdose. This paper describes a case where electrocardiography
      changes mimic inferior myocardial infarction during the course of chronic lithium
      treatment in an elderly patient. The patient's electrocardiography changes were
      partially resolved after hemodialysis.

PMID- 20690100
TI  - Right heart thrombus-in-transit with pulmonary embolism in a patient with primary
      hypercoagulable state.
AB  - A 25 year-old female with a history of Caesarian section ten weeks ago presented
      with symptoms suggestive of pulmonary embolism. Transthoracic echocardiography
      revealed a free-floating large thrombus traversing the right atrial cavity.
      Transesophageal echocardiography confirmed the presence of an unattached thrombus
      that originated from the most proximal part of the inferior vena cava. Multi
      slice computed tomography of the chest and abdomen revealed the thrombus to start
      from the intra-hepatic part of the inferior vena cava and extend through the
      right atrium. It also demonstrated multiple thrombi in the pulmonary vasculature,
      the largest being in the right main pulmonary artery and its lower lobe branch.
      The patient was triaged for surgical embolectomy under cardio-pulmonary bypass.
      Follow-up trans-thoracic and transesophageal echocardiography confirmed adequate
      removal of the thrombus. By genetic examination, she proved to have factor V
      'Leiden' gene and two thrombophilia genes, all of which were positive in the
      heterozygous state. She had also a high serum homocysteine.

PMID- 20690101
TI  - Congenital musculoskeletal abnormalities associated with aortic, pulmonary and
      iliac aneurysms.
AB  - We present the case of a young patient with severe congenital musculoskeletal
      abnormalities. associated with different pathologies, with involvement of the
      arterial tree on both the systemic and pulmonary circulation, and involvement of
      the lungs due to thoracic hypoplasia. The presence of such extensive pathology
      raises the question of the suitability of such patients to undergo major
      corrective cardiac surgery procedures.

PMID- 20690102
TI  - Ebstein's anomaly with Brugada-like electrocardiogram pattern: a critical view.

PMID- 20690103
TI  - A scientific repository to support the research and development of technologies
      related to quantitative electrocardiography: the Telemetric and Holter ECG
      Warehouse (THEW).
AB  - We implemented an ECG data-warehousing project to promote cross-fertilization of
      scientific knowledge, resources and ideas that will advance the understanding of
      quantitative ECG and cardiac safety. While other open ECG databases are
      available, our Telemetric and Holter ECG Warehouse (THEW) proposes unique sets of
      continuous digital ECGs recorded in cardiac patients, healthy individuals and
      individuals exposed to non-cardiac and cardiac drugs. In this paper, we present
      briefly the content and the current research triggered by this initiative.

PMID- 20690104
TI  - Is it possible to accurately differentiate neurocardiogenic syncope from
      epilepsy?
AB  - Global cerebral hypoperfusion resulting in syncope, and asynchronous discharge of
      cerebral neurons leading to seizure, are two major mechanisms of transient loss
      of consciousness. They both have a lot in common in clinical and historical
      settings, although with a high prevalence of incorrect diagnosis, even by well
      trained staff. The aim of this review was to try to combine data from both a
      cardiologist's and a neurologist's perspective (history taking, special
      questionnaires, serum prolactin, EEG, CT/MRI, tilt-testing, loop recorders).

PMID- 20690105
TI  - Sunao Tawara: discoverer of the atrioventricular conduction system of the heart.

PMID- 20690107
TI  - Involvement of mitochondrial activity in mediating ELF-EMF stimulatory effect on
      human sperm motility.
AB  - It has recently been reported that the exposure of human spermatozoa to an
      extremely low frequency (ELF) electromagnetic field (EMF) with a square waveform
      of 5 mT amplitude and frequency of 50 Hz improves sperm motility. The functional
      relationship between the energy metabolism and the enhancement of human sperm
      motility induced by ELF-EMF was investigated. Sperm exposure to ELF-EMF resulted
      in a progressive and significant increase of mitochondrial membrane potential and
      levels of ATP, ADP and NAD(+) that was associated with a progressive and
      significant increase in the sperm kinematic parameters. No significant effects
      were detected on other parameters such as ATP/ADP ratio and energy charge. When
      carbamoyl cyanide m-chlorophenylhydrazone (CICCP) was applied to inhibit the
      oxidative phosphorylation in the mitochondria, the values of energy parameters
      and motility in the sperm incubated in the presence of glucose and exposed to ELF
      EMF did not change, thus indicating that the glycolysis was not involved in
      mediating ELF-EMF stimulatory effect on motility. By contrast, when pyruvate and
      lactate were provided instead of glucose, the energy status and motility
      increased significantly in ELF-EMF-treated sperm. Under these culture conditions,
      the inhibition of glycolitic metabolism by 2-deoxy-D-glucose (DOG) again resulted
      in increased values of energy and kinematic parameters, indicating that
      gluconeogenesis was not involved in producing glucose for use in glycolysis. We
      concluded that the key role in mediating the stimulatory effects exerted by ELF
      EMF on human sperm motility is played by mitochondrial oxidative phosphorylation
      rather than glycolysis.

PMID- 20690108
TI  - Nonparametric sequential monitoring of longitudinal trials.
AB  - This paper considers the sequential monitoring of multi-armed longitudinal
      clinical trials. We describe an approach that is relatively simple and
      accessible. Sequential ranks are used to form partial sum statistics, yielding
      processes that have independent increments, and hence can be approximated by
      Brownian motions. Three monitoring procedures are proposed. The first two are
      asymptotic, continuous analogues of the well-known Pocock and O'Brien-Fleming
      group sequential procedures, whereas the third procedure is exact. Performance of
      the procedures is assessed using Monte Carlo simulations. Data from an
      orthodontic clinical trial is used to illustrate the proposed methods, for the
      comparison of three treatment groups.

PMID- 20690109
TI  - What can go wrong when ignoring correlation bounds in the use of generalized
      estimating equations.
AB  - The analysis of repeated measure or clustered data is often complicated by the
      presence of correlation. Further complications arise for discrete responses,
      where the marginal probability-dependent Frechet bounds impose feasibility limits
      on the correlation that are often more restrictive than the positive definite
      range. Some popular statistical methods, such as generalized estimating equations
      (GEE), ignore these bounds, and as such can generate erroneous estimates and lead
      to incorrect inferential results. In this paper, we discuss two alternative
      strategies: (i) using QIC to select a data-driven correlation value within the
      Frechet bounds, and (ii) the use of likelihood-based latent variable modeling,
      such as multivariate probit, to get around the problem all together. We provide
      two examples of the repercussions of incorrectly using existing GEE software in
      the presence of correlated binary responses.

PMID- 20690110
TI  - Covariate adjusted weighted normal spatial scan statistics with applications to
      study geographic clustering of obesity and lung cancer mortality in the United
      States.
AB  - In the field of cluster detection, a weighted normal model-based scan statistic
      was recently developed to analyze regional continuous data and to evaluate the
      clustering pattern of pre-defined cells (such as state, county, tract, school,
      hospital) that include many individuals. The continuous measures of interest are,
      for example, the survival rate, mortality rate, length of physical activity, or
      the obesity measure, namely, body mass index, at the cell level with an
      uncertainty measure for each cell. In this paper, we extend the method to search
      for clusters of the cells after adjusting for single/multiple
      categorical/continuous covariates. We apply the proposed method to 1999-2003
      obesity data in the United States (US) collected by CDC's Behavioral Risk Factor
      Surveillance System with adjustment for age and race, and to 1999-2003 lung
      cancer age-adjusted mortality data by gender in the United States from the
      Surveillance Epidemiology and End Results (SEER Program) with adjustment for
      smoking and income.

PMID- 20690111
TI  - Angiotensin-I converting enzyme inhibitory and antioxidant activities of peptide
      fractions extracted by ultrafiltration of cowpea Vigna unguiculata hydrolysates.
AB  - BACKGROUND: Enzymatic proteolysis of food proteins is used to produce peptide
      fractions with the potential to act as physiological modulators. Fractionation of
      these proteins by ultrafiltration results in fractions rich in small peptides
      with the potential to act as functional food ingredients. The present study
      investigated the angiotensin-I converting enzyme (ACE-I) inhibitory and
      antioxidant activities for hydrolysates produced by hydrolyzing Vigna unguiculata
      protein extract as well as ultrafiltered peptide fractions from these
      hydrolysates. RESULTS: Alcalase((r)), Flavourzyme((r)) and pepsin-pancreatin were
      used to produce extensively hydrolyzed V. unguiculata protein extract. Degree of
      hydrolysis (DH) differed between the enzymatic systems and ranged from 35.7% to
      58.8%. Fractionation increased in vitro biological activities in the peptide
      fractions, with IC(50) (hydrolysate concentration in ug protein mL(-1) required
      to produce 50% ACE inhibition) value ranges of 24.3-123 (Alcalase hydrolysate,
      AH), 0.04-170.6 (Flavourzyme hydrolysate; FH) and 44.7-112 (pepsin-pancreatin
      hydrolysate, PPH) ug mL(-1), and TEAC (Trolox equivalent antioxidant coefficient)
      value ranges of 303.2-1457 (AH), 357.4-10 211 (FH) and 267.1-2830.4 (PPH) mmol L(
      1) mg(-1) protein. CONCLUSION: The results indicate the possibility of obtaining
      bioactive peptides from V. unguiculata proteins by means of a controlled protein
      hydrolysis using Alcalase((r)), Flavourzyme((r)) and pepsin-pancreatin. The V.
      unguiculata protein hydrolysates and their corresponding ultrafiltered peptide
      fractions might be utilized for physiologically functional foods with
      antihypertensive and antioxidant activities.

PMID- 20690112
TI  - What is the evidence for the use of mindfulness-based interventions in cancer
      care? A review.
AB  - OBJECTIVE: The aim of this paper is to present and critically appraise the
      evidence for the use of mindfulness-based interventions in cancer care. METHODS:
      Systematic review methods were used. A thorough search of relevant major and
      specialised electronic databases was made and unpublished and ongoing work was
      also identified. Both qualitative and quantitative studies were eligible for
      inclusion. Information about aims, design, participant sample, measures, findings
      and intervention details were extracted from each study. RESULTS: Thirteen
      research papers and four conference abstracts published since 2007 were
      identified which met the criteria, reporting five different types of mindfulness
      intervention. The 13 papers composed of three randomised control trials, two non
      randomised control trials, five pre and post-test designs and two qualitative
      studies. Studies report significant improvements in anxiety, depression, stress,
      sexual difficulties, physiological arousal and immune function or subjective
      benefits across all interventions. Methodological limitations were identified.
      Diversity in study designs and interventions makes comparisons between studies
      difficult. Some mindfulness interventions may have a place in acute treatment and
      palliative care. CONCLUSION: Mindfulness approaches are a promising intervention
      in cancer care, potentially across the cancer trajectory. Further qualitative
      research and research into different styles of mindfulness delivery are
      recommended.

PMID- 20690113
TI  - The contribution of self-esteem and self-concept in psychological distress in
      women at risk of hereditary breast cancer.
AB  - OBJECTIVE: Clarification of the role of several aspects of self-concept regarding
      psychological distress in women at risk of hereditary breast cancer will help to
      target counselling and psychosocial interventions more appropriately. In this
      study, we aimed (1) to examine the role of general self-esteem and specific
      aspects of self-concept (i.e. stigma, vulnerability, and mastery) in
      psychological distress in women at risk of hereditary breast cancer and (2) to
      compare the relative importance of these self-concept aspects in psychological
      distress in women with low versus high self-esteem. METHODS: General and breast
      cancer-specific distress, self-esteem, self-concept, and demographics were
      assessed in 246 women being at risk of hereditary breast cancer, who opted either
      for regular breast surveillance or prophylactic surgery. RESULTS: In the total
      study group, self-esteem was negatively associated with general distress.
      Furthermore, feeling stigmatized was strongly associated with more breast-cancer
      specific distress, and to a lesser degree with general distress. In women with
      low-self esteem, feelings of stigmatization were strongly associated with higher
      levels of both breast-cancer-specific and general distress, while a sense of
      mastery was associated with less general distress. For women with high self
      esteem, feelings of both stigmatization and vulnerability were associated with
      more breast-cancer-specific distress, whereas there were no significant
      associations with general distress. DISCUSSION: Psychosocial interventions or
      support groups for women at risk of hereditary breast cancer should focus on self
      esteem and feelings of stigmatization and isolation, and consequently tailor the
      interventions on specific items for respective women.

PMID- 20690114
TI  - Comparison of lasting life changes after cancer and BMT: perspectives of long
      term survivors and spouses.
AB  - OBJECTIVE: This qualitative follow up of long-term (>5 years) cancer survivor and
      spouse participants from a large, previous study of quality of life after blood
      and marrow transplantation (BMT) was designed to gain a deeper understanding of
      lasting life changes they experienced. METHODS: Thirty spouse-survivor pairs, an
      average of 13 years post-BMT, were individually interviewed to identify lasting
      life changes. Participants were asked about their most significant long-lasting
      change since cancer/BMT, most significant positive change and negative change,
      and whether the experience had affected them and their spouse differently.
      RESULTS: Spouses and survivors spontaneously identified both positive and
      negative changes. Spouses reported a higher proportion of negative changes (24%)
      than did survivors (15%), and survivors a higher proportion of positive changes
      (85%) than spouses (76%). For both groups, the most frequent positive change was
      in 'perspective/outlook on life' and negative change was 'lingering health
      effects,' although survivors mentioned the latter twice as often as did spouses.
      Spouses were more likely to talk about changes in the first-person plural (we,
      us) that were largely emotional or in relation to the survivor, whereas survivors
      spoke of changes in the first-person singular (I, me) that occurred to them
      directly and were largely physical. CONCLUSIONS: Although both spouses and
      survivors described similar negative and positive long-lasting changes that
      continued an average of 13 years post-BMT, they reported differences in the ways
      they were impacted by the experience, which was reflected in the language they
      used. Implications for future studies, family education, and couples-based
      interventions are discussed.

PMID- 20690115
TI  - CEP290, a gene with many faces: mutation overview and presentation of CEP290base.
AB  - Ciliopathies are an emerging group of disorders, caused by mutations in ciliary
      genes. One of the most intriguing disease genes associated with ciliopathies is
      CEP290, in which mutations cause a wide variety of distinct phenotypes, ranging
      from isolated blindness over Senior-Loken syndrome (SLS), nephronophthisis
      (NPHP), Joubert syndrome (related disorders) (JS[RD]), Bardet-Biedl syndrome
      (BBS), to the lethal Meckel-Gruber syndrome (MKS). Despite the identification of
      over 100 unique CEP290 mutations, no clear genotype-phenotype correlations could
      yet be established, and consequently the predictive power of a CEP290-related
      genotype remains limited. One of the challenges is a better understanding of
      second-site modifiers. In this respect, there is a growing interest in the
      potential modifying effects of variations in genes encoding other members of the
      ciliary proteome that interact with CEP290. Here, we provide an overview of all
      CEP290 mutations identified so far, with their associated phenotypes. To this
      end, we developed CEP290base, a locus-specific mutation database that links
      mutations with patients and their phenotypes (medgen.ugent.be/cep290base).

PMID- 20690116
TI  - High-throughput sequencing of a 4.1 Mb linkage interval reveals FLVCR2 deletions
      and mutations in lethal cerebral vasculopathy.
AB  - Rare lethal disease gene identification remains a challenging issue, but it is
      amenable to new techniques in high-throughput sequencing (HTS). Cerebral
      proliferative glomeruloid vasculopathy (PGV), or Fowler syndrome, is a severe
      autosomal recessive disorder of brain angiogenesis, resulting in abnormally
      thickened and aberrant perforating vessels leading to hydranencephaly. In three
      multiplex consanguineous families, genome-wide SNP analysis identified a locus of
      14 Mb on chromosome 14. In addition, 280 consecutive SNPs were identical in two
      Turkish families unknown to be related, suggesting a founder mutation reducing
      the interval to 4.1 Mb. To identify the causative gene, we then specifically
      enriched for this region with sequence capture and performed HTS in a proband of
      seven families. Due to technical constraints related to the disease, the average
      coverage was only 7*. Nonetheless, iterative bioinformatic analyses of the
      sequence data identified mutations and a large deletion in the FLVCR2 gene,
      encoding a 12 transmembrane domain-containing putative transporter. A striking
      absence of alpha-smooth muscle actin immunostaining in abnormal vessels in fetal
      PGV brains, suggests a deficit in pericytes, cells essential for capillary
      stabilization and remodeling during brain angiogenesis. This is the first lethal
      disease-causing gene to be identified by comprehensive HTS of an entire linkage
      interval.

PMID- 20690117
TI  - Structural and electronic effects of carbon-supported Pt(x)Pd(1-x) nanoparticles
      on the electrocatalytic activity of the oxygen-reduction reaction and on methanol
      tolerance.
AB  - We report a systematic investigation on the structural and electronic effects of
      carbon-supported Pt(x)Pd(1-x) bimetallic nanoparticles on the oxygen reduction
      reaction (ORR) and methanol oxidation reaction (MOR) in acid electrolyte.
      Pt(x)Pd(1-x)/C nanocatalysts with various Pt/Pd atomic ratios (x=0.25, 0.5, and
      0.75) were synthesized by using a borohydride-reduction method. Rotating-disk
      electrode measurements revealed that the Pt(3)Pd(1)/C nanocatalyst has a
      synergistic effect on the ORR, showing 50% enhancement, and an antagonistic
      effect on the MOR, showing 90% reduction, relative to JM 20 Pt/C on a mass basis.
      The extent of alloying and Pt d-band vacancies of the Pt(x)Pd(1-x)/C
      nanocatalysts were explored by extended X-ray absorption fine-structure
      spectroscopy (EXAFS) and X-ray absorption near-edge structure spectroscopy
      (XANES). The structure-activity relationship indicates that ORR activity and
      methanol tolerance of the nanocatalysts strongly depend on their extent of
      alloying and d-band vacancies. The optimal composition for enhanced ORR activity
      is Pt(3)Pd(1)/C, with high extent of alloying and low Pt d-band vacancies, owing
      to favorable O-O scission and inhibited formation of oxygenated intermediates.
      MOR activity also shows structure dependence. For example, Pt(1)Pd(3)/C with
      Pt(rich-core)Pd(rich-shell) structure possesses lower MOR activity than the
      Pt(3)Pd(1)/C nanocatalyst with random alloy structure. Herein, extent of alloying
      and d-band vacancies reveal new insights into the synergistic and antagonistic
      effects of the Pt(x)Pd(1-x)/C nanocatalysts on surface reactivity.

PMID- 20690118
TI  - Highly ordered mesoporous cobalt oxide nanostructures: synthesis,
      characterisation, magnetic properties, and applications for electrochemical
      energy devices.
AB  - Highly ordered mesoporous Co(3)O(4) nanostructures were prepared using KIT-6 and
      SBA-15 silica as hard templates. The structures were confirmed by small angle X
      ray diffraction, high resolution transmission electron microscopy, and N(2)
      adsorption-desorption isotherm analysis. Both KIT-6 cubic and SBA-15 hexagonal
      mesoporous Co(3)O(4) samples exhibited a low Neel temperature and bulk
      antiferromagnetic coupling due to geometric confinement of antiferromagnetic
      order within the nanoparticles. Mesoporous Co(3)O(4) electrode materials have
      demonstrated the high lithium storage capacity of more than 1200 mAh g(-1) with
      an excellent cycle life. They also exhibited a high specific capacitance of 370 F
      g(-1) as electrodes in supercapacitors.

PMID- 20690119
TI  - Construction of a novel topological frustrated system: a frustrated metal cluster
      in a helical space.
AB  - A novel topologically frustrated pentanuclear cluster helicate [{Cu(II)(MU
      L)(3)}(2)Cu(II) (3)(MU(3)-OH)](3+) (L(-)=3,5-bis(2-pyridyl)pyrazolate) has been
      synthesized and characterized. This cluster has a helical arrangement of ligands
      around the central metal core. Dzyaloshinsky-Moriya interactions are essential
      components to observe a gradual magnetization and forbidden transitions of high
      field/multi-frequency (HF/MF)-ESR. The origin of the magnetic anisotropy of this
      compound is influenced by its helical spin structure, and consequently, the Cu(5)
      cluster helicate introduces a unique magnetic anisotropy. This observation is a
      direct evidence of the topological part of the new spin phase in a magnetic
      system.

PMID- 20690120
TI  - Palladium-catalyzed addition of silyl-substituted chloroalkynes to terminal
      alkynes.

PMID- 20690121
TI  - ADLOC: an aptamer-displacement assay based on luminescent oxygen channeling.
AB  - Functional nucleic acids, such as aptamers and allosteric ribozymes, can sense
      their ligands specifically, thereby undergoing structural alterations that can be
      converted into a detectable signal. The direct coupling of molecular recognition
      to signal generation enables the production of versatile reporters that can be
      applied as molecular probes for various purposes, including high-throughput
      screening. Here we describe an unprecedented type of a nucleic acid-based sensor
      system and show that it is amenable to high-throughput screening (HTS)
      applications. The approach detects the displacement of an aptamer from its bound
      protein partner by means of luminescent oxygen channeling. In a proof-of
      principle study we demonstrate that the format is feasible for efficient
      identification of small drug-like molecules that bind to a protein target, in
      this case to the Sec7 domain of cytohesin. We extended the approach to a new
      cytohesin-specific single chain DNA aptamer, C10.41, which exhibits a similar
      binding behavior to cytohesins but has the advantage of being more stable and
      easier to synthesize and to modify than the RNA-aptamer M69. The results obtained
      with both aptamers indicate the general suitability of the aptamer-displacement
      assay based on luminescent oxygen channelling (ADLOC) for HTS. We also analyzed
      the potential for false positive hits and identified from a library of 18,000
      drug-like small molecules two compounds as strong singlet-oxygen quenchers. With
      full automation and the use of commercially available plate readers, we estimate
      that the ADLOC-based assay described here could be used to screen at least
      100,000 compounds per day.

PMID- 20690122
TI  - Gold(I) and Bronsted acid catalyzed intramolecular rearrangements of
      vinylidenecyclopropanes.

PMID- 20690123
TI  - Isovitamin B12: a vitamin B12 derivative that flips its tail.

PMID- 20690124
TI  - Right parietal brain activity precedes perceptual alternation during binocular
      rivalry.
AB  - We investigated perceptual reversals for intermittently presented stimuli during
      binocular rivalry and physical alternation while the ongoing EEG was recorded
      from 64 channels. EEG topographies immediately preceding stimulus-onset were
      analyzed and two topographies doubly dissociated perceptual reversals from non
      reversals. The estimated intracranial generators associated with these
      topographies were stronger in right inferior parietal cortex and weaker
      bilaterally in the ventral stream before perceptual reversals. No such
      differences were found for physical alternation of the same stimuli. These
      results replicate and extend findings from a previous study with the Necker cube
      and suggest common neural mechanisms associated with perceptual reversals during
      binocular rivalry and ambiguous figure perception. For both types of multi-stable
      stimuli, the dorsal stream is more active preceding perceptual reversals.
      Activity in the ventral stream, however, differed for binocular rivalry compared
      to ambiguous figures. The results from the two studies suggest a causal role for
      the right inferior parietal cortex in generating perceptual reversals regardless
      of the type of multi-stable stimulus, while activity in the ventral stream
      appears to depend on the particular type of stimulus.

PMID- 20690125
TI  - Adolescent group empowerment: Group-centred occupations to empower adolescents
      with disabilities in the urban slums of North India.
AB  - This study aimed to understand how adolescents with disabilities can assume
      greater control over their rehabilitation and participation within a community
      based rehabilitation programme in the urban slums of North India. A critical
      ethnographical approach using multiple qualitative and participatory data
      collection methods was adopted. Fieldwork was conducted from January to May 2005
      and October 2006 to March 2007 with 21 adolescents with and 11 adolescents
      without disabilities (aged 12 to 18 years), and 10 community-based rehabilitation
      staff members. A conceptual framework called the 'Adolescent Group Empowerment
      Pyramid' was developed. Four themes informed the framework: group participation,
      group demonstration, group recognition and the socio-cultural environment's
      interaction with disability. Group empowerment, achieved through group-centred
      occupations, encourages adolescents to work together to address their
      rehabilitation challenges and agendas. Three external support factors and 10
      areas for nurturing the group empowerment process also emerged. A limitation of
      this study is the lack of data on how the familial and local political and
      economic environment impact adolescents' ability to make decisions about their
      rehabilitation. Further research might explore group occupations and occupational
      recognition, and what this means for social change and the personal and
      collective growth of adolescents in underserviced communities.

PMID- 20690126
TI  - Examining the phonological neighborhood density effect using near infrared
      spectroscopy.
AB  - Phonological density refers to the number of words that can be generated by
      replacing a phoneme in a target word with another phoneme in the same position.
      Although the precise nature of the phonological neighborhood density effect is
      not firmly established, many behavioral psycholinguistic studies have shown that
      visual recognition of individual words is influenced by the number and type of
      neighbors the words have. This study explored neurobehavioral correlates of
      phonological neighborhood density in skilled readers of English using near
      infrared spectroscopy. On the basis of a lexical decision task, our findings
      showed that words with many phonological neighbors (e.g., FRUIT) were recognized
      more slowly than words with few phonological neighbors (e.g., PROOF), and that
      words with many neighbors elicited significantly greater changes in blood
      oxygenation in the left than in the right hemisphere of the brain, specifically
      in the areas BA 22/39/40. In previous studies these brain areas have been
      implicated in fine-grained phonological processing in readers of English. The
      present findings provide the first demonstration that areas BA 22/39/40 are also
      sensitive to phonological density effects.

PMID- 20690127
TI  - Synthesis and characterisation of alpha-Glycosyloxyamides derived from cyanogenic
      glycosides.
AB  - INTRODUCTION: After exposure to oxidative stress, the leaves of some cyanogenic
      plants contain primary alpha-glycosyloxyamides with structures corresponding to
      their original cyanogenic glycosides. OBJECTIVES: The aim of this study was to
      prepare such amides from their nitrile precursors and to characterise the new
      substances in order to facilitate their early identification in forthcoming
      studies. Methods - A simple but highly specific method is described for the in
      vitro synthesis of the amides from their nitrile glycoside precursors using the
      Radziszewski reaction with hydrogen peroxide and a single-step purification of
      the reaction product. A TLC method is presented for the preliminary and fast
      identification of the alpha-glycosyloxyamides. RESULTS: Following this procedure,
      seven representative alpha-glycosyloxyamides, five of them new, were obtained and
      analytically characterised by means of (1) H, (13) C NMR and ATR-IR spectroscopy,
      highlighting the differences from their respective nitrile glycoside precursors.
      CONCLUSION: Thus, alpha-glycosyloxyamides can be obtained in sufficient amounts
      and purity to serve as references for further studies on the catabolism of
      cyanogenic glycosides and the detoxification of cyanogenic foodplants using the
      new aspect of nitrile hydrolysis with (endogenous) hydrogen peroxide.

PMID- 20690128
TI  - Cardiovascular disease and death associated with depression and antidepressants
      in the Melbourne Longitudinal Studies on Healthy Ageing (MELSHA).
AB  - BACKGROUND: Cardiovascular disease (CVD) and death may be associated with
      depression and antidepressants, but published findings remain equivocal. The
      authors aimed to determine the risk of CVD incidence and death associated with
      several classifications of depression. METHODS: A prospective cohort study was
      conducted (1994-2006) in a regionally representative sample of 1000 non
      institutionalised older Australians age 65+ years (47% men). Endpoints were non
      fatal CVD incidence and death over 10 and 12-years, respectively. Depression
      incidence was assessed at 2-years. Depression related predictors were defined by
      symptoms (Psychogeriatric Assessment Scales, depression scale) and/or
      antidepressants to determine independent and/or joint effects on endpoints. Cox
      regressions determined unadjusted and multiple-adjusted (for significant
      covariates) hazard ratios (HR). RESULTS: Baseline response rate was 70.3%.
      Aggregate dropout rate was approximately 24% for survivors at biennial follow
      ups, but death status was ascertained for all participants. Several
      classifications of depression predicted death in unadjusted analyses (39-60% >1),
      but effects disappeared in multiple-adjusted analyses (in which all HRs became <1
      and non-significant). Depression related predictors were thus not associated with
      CVD incidence; or death after accounting for confounding mostly by CVD, diabetes
      and poor functional health covariates. Prevalent arthritis, respiratory disease
      and daily pain were predictors (P < 0.05) of depression incidence. CONCLUSIONS:
      Depression related predictors were not independently associated with CVD
      incidence or death in older people. Antidepressants were not associated with CVD
      or premature death, accounting for whether participants' remained symptomatic or
      not. Depression co-occurs with and might be partly caused by chronic disease and
      poor functional health.

PMID- 20690129
TI  - An examination of the Boston Naming Test: calculation of "estimated" 60-item
      score from 30- and 15-item scores in a cognitively impaired population.
AB  - OBJECTIVE: Multiple versions of the Boston Naming Test (BNT) exist, which makes
      comparison of findings from different studies difficult. The current project
      sought to determine if estimated 60-item BNT scores could be reliably calculated
      from 30- and 15-item administrations with patients diagnosed with Alzheimer's
      disease (AD). METHODS: Estimated 60-item scores were created for 30-item (even
      and odd) and 15-item Consortium to Establish a Registry for Alzheimer's disease
      (CERAD) versions of the BNT from a database containing item-level responses for
      all BNT items. Correlations were conducted between all three estimated 60-item
      scores and full 60-item version scores administered to all participants in the
      sample. RESULTS: The estimated versions were all highly correlated with the
      standard 60-item version of the BNT across the sample and these findings held
      when the sample was separated out by case (AD) and control status. Mean
      difference scores were very small for scores estimated from 30-item
      administrations; however, difference scores for the 15-item CERAD were much
      larger. CONCLUSIONS: Estimated 60-item versions of the BNT can be created from 30
      item BNT administrations, which will enable comparisons across studies and allow
      integration of data from various AD research groups for increased power in
      analytic protocols. Creation of an estimated score from the 15-item CERAD version
      is not warranted.

PMID- 20690130
TI  - From single-pulsed field gradient to double-pulsed field gradient MR: gleaning
      new microstructural information and developing new forms of contrast in MRI.
AB  - One of the hallmarks of diffusion NMR and MRI is its ability to utilize
      restricted diffusion to probe compartments much smaller than the excited volume
      or the MRI voxel, respectively, and to extract microstructural information from
      them. Single-pulsed field gradient (s-PFG) MR methodologies have been employed
      with great success to probe microstructures in various disciplines, ranging from
      chemistry to neuroscience. However, s-PFG MR also suffers from inherent
      shortcomings, especially when specimens are characterized by orientation or size
      distributions: in such cases, the microstructural information available from s
      PFG experiments is limited or lost. Double-pulsed field gradient (d-PFG) MR
      methodology, an extension of s-PFG MR, has attracted attention owing to recent
      theoretical studies predicting that it can overcome certain inherent limitations
      of s-PFG MR. In this review, we survey the microstructural features that can be
      obtained from conventional s-PFG methods in the different q regimes, and
      highlight its limitations. The experimental aspects of d-PFG methodology are then
      presented, together with an overview of its theoretical underpinnings and a
      general framework for relating the MR signal decay and material microstructure,
      affording new microstructural parameters. We then discuss recent studies that
      have validated the theory using phantoms in which the ground truth is well known
      a priori, a crucial step prior to the application of d-PFG methodology in
      neuronal tissue. The experimental findings are in excellent agreement with the
      theoretical predictions and reveal, inter alia, zero-crossings of the signal
      decay, robustness towards size distributions and angular dependences of the
      signal decay from which accurate microstructural parameters, such as compartment
      size and even shape, can be extracted. Finally, we show some initial findings in
      d-PFG MR imaging. This review lays the foundation for future studies, in which
      accurate and novel microstructural information could be extracted from complex
      biological specimens, eventually leading to new forms of contrast in MRI.

PMID- 20690131
TI  - Assessing neuropsychiatric symptoms in nursing home patients with dementia:
      reliability and Reliable Change Index of the Neuropsychiatric Inventory and the
      Cohen-Mansfield Agitation Inventory.
AB  - OBJECTIVE: The aim of the study was to estimate inter-observer and test-retest
      reliability of the Neuropsychiatric Inventory Nursing Home version (NPI-NH) and
      the Cohen-Mansfield Agitation Inventory (CMAI), and to establish their Reliable
      Change Index (RCI). Reliable Change methodology is a practical method for
      estimating the least change acquired in outcome measures. METHODS: Nursing home
      physicians and certified nurses assessed 105 patients with dementia (in five
      nursing homes) at baseline and after 2 weeks. Spearman rank correlations were
      calculated and Reliable Change Difference Scores (S(diff) (80)). RESULTS: NPI-NH
      inter-observer correlations ranged 0.14-0.70. NPI-NH test-retest correlations
      ranged 0.23-0.80. CMAI inter-observer correlations ranged -0.10 to 0.72. CMAI
      test-retest correlations ranged 0.32-1.00 (CMAI total score, rho=0.89). S(diff)
      (80) for NPI-NH items ranged 1.7-5.0. A change of 11 points on the NPI-NH total
      score can be considered a true behavioral change. S(diff) (80) for CMAI total
      score was 8 and factor analysis based sub-scale scores physically aggressive
      behavior, physically non-aggressive behavior, and verbally agitated behavior were
      3, 6, and 4, respectively. CONCLUSION: Reliability estimates and RCI for the NPI
      NH were modest, seriously challenging its reliability and sensitivity to change
      over time. NPI-NH may only be useful for monitoring behavioral changes in
      individual patients with dementia, when symptoms are moderate to severe, or when
      effect sizes are large. Reliability of the CMAI was good, supporting its
      usefulness in clinical practice. Poor inter-observer agreement on behavioral
      observations poses a real challenge in nursing homes. Reliable scales are needed
      that include unambiguously formulated items.

PMID- 20690132
TI  - Abuse of older Chinese with dementia by family caregivers: an inquiry into the
      role of caregiver burden.
AB  - OBJECTIVE: This study examined the prevalence and risk factors for elder abuse in
      older Chinese with dementia by their family caregivers in Hong Kong. METHODS: A
      sample of 122 family caregivers of older persons with dementia was conveniently
      recruited from local community centers for the elderly. Participants provided
      information on their demographic characteristics, care recipients' physical
      functioning and agitated behavior, caregiver burden, and whether they had
      directed any abusive behavior at the care recipients in the previous month.
      RESULTS: Sixty-two and 18 per cent of the caregivers reported having verbally or
      physically abused the care recipients in the past month. Family caregivers who
      spent more days co-residing with the care recipients, lacked any assistance from
      a domestic helper, observed more agitated behaviors in the care recipients,
      and/or reported a higher level of caregiver stress, reported more abusive
      behaviors. The results of hierarchical regression analysis showed that the number
      of co-residing days (p < 0.001), lack of any assistance from a domestic helper (p
      < 0.05), and caregiver burden (p < 0.01) were significant predictors of verbal
      abuse. Care recipient agitated behavior (p < 0.01) also predicted verbal abuse,
      with its effect mediated by caregiver burden. For physical abuse, the number of
      co-residing days (p < 0.01) was the only significant predictor. CONCLUSIONS:
      Verbal and physical abuse were highly prevalent among this population of older
      Chinese with dementia. A higher level of caregiver stress is related to a higher
      level of verbal, but not physical abuse inflicted by the caregivers of these
      older persons with dementia.

PMID- 20690133
TI  - Mesoporous silica nanoparticles for intracellular controlled drug delivery.
AB  - The application of nanotechnology in the field of drug delivery has attracted
      much attention in the latest decades. Recent breakthroughs on the morphology
      control and surface functionalization of inorganic-based delivery vehicles, such
      as mesoporous silica nanoparticles (MSNs), have brought new possibilities to this
      burgeoning area of research. The ability to functionalize the surface of
      mesoporous-silica-based nanocarriers with stimuli-responsive groups,
      nanoparticles, polymers, and proteins that work as caps and gatekeepers for
      controlled release of various cargos is just one of the exciting results reported
      in the literature that highlights MSNs as a promising platform for various
      biotechnological and biomedical applications. This review focuses on the most
      recent progresses in the application of MSNs for intracellular drug delivery. The
      latest research on the pathways of entry into live mammalian and plant cells
      together with intracellular trafficking are described. One of the main areas of
      interest in this field is the development of site-specific drug delivery
      vehicles; the contribution of MSNs toward this topic is also summarized. In
      addition, the current research progress on the biocompatibility of this material
      in vitro and in vivo is discussed. Finally, the latest breakthroughs for
      intracellular controlled drug release using stimuli-responsive mesoporous-silica
      based systems are described.

PMID- 20690134
TI  - Enhancement of ionic conductivity in Sm-doped ceria/yttria-stabilized zirconia
      heteroepitaxial structures.

PMID- 20690135
TI  - Modeling size and shape effects on the order-disorder phase-transition
      temperature of CoPt nanoparticles.

PMID- 20690136
TI  - Mechanical fatigue of hybrid glasses.

PMID- 20690137
TI  - Monosteps on the surfaces of mesostructured silica and titania thin films.

PMID- 20690138
TI  - Inhibition of androgen receptor functions by gelsolin FxxFF peptide delivered by
      transfection, cell-penetrating peptides, and lentiviral infection.
AB  - BACKGROUND: Prostate cancer (PC) growth is dependent on the androgen-androgen
      receptor (AR) axis. Because current androgen ablation therapies of PC lead to
      resistance, novel approaches to block AR activity are urgently needed. METHODS:
      We inhibited AR function beyond the level of hormone binding by blockade of the
      coactivator groove in the ligand-binding domain (LBD) using a high-affinity
      gelsolin FxxFF peptide. Following peptide selection, the effect of the gelsolin
      FxxFF peptide on AR functions was determined in Hep3B cells that were transiently
      transfected with pM-peptide expression vectors or were incubated with synthetic
      gelsolin FxxFF peptide coupled to the TAT cell-penetrating peptide. Lentiviruses
      expressing the gelsolin FxxFF peptide were used to study endogenous AR target
      gene expression in LNCaP cells. RESULTS: pM-Gelsolin FxxFF efficiently interfered
      with AR N/C interaction and specifically inhibited AR-regulated reporter gene
      activity. The peptide did not inhibit progesterone receptor (PR) and
      glucocorticoid receptor (GR) activity, nor constitutively active gene promoters.
      The peptide also specifically blocked in vitro interactions of AR LBD with
      peptides. Like the gelsolin FxxFF peptide expressed by an expression vector,
      synthetic TAT-gelsolin FxxFF peptide efficiently blocked AR N/C interaction and
      inhibited full-length AR-regulated reporter gene activity. It hardly affected PR
      and GR activity, but the effect on constitutively active promoters was variable.
      Lentiviral gelsolin FxxFF peptide inhibited expression of KLK2 and NDRG1, but
      hardly affected PSA and TMPRSS2. CONCLUSIONS: Our results show that the AR
      coactivator groove may function as a target to overcome therapeutic failure that
      arises during current androgen ablation therapies.

PMID- 20690139
TI  - Meta-analysis of genome-wide and replication association studies on prostate
      cancer.
AB  - BACKGROUND: Genome-wide and replication association studies (GWAs) have
      identified multiple loci at which common variants modestly influence the risk of
      developing prostate cancer (PCa). To enhance the power to identify loci
      associated with PCa, we constructed a meta-analysis of GWAs on PCa. METHODS:
      Articles evaluating the effects of genome-wide SNPs on PCa were identified by
      searching the PubMed database. After extraction of relevant data, main and
      subgroup meta-analyses were performed to assess the effects of relevant SNPs on
      PCa. RESULTS: 21 eligible articles containing 71 subgroups were included in this
      meta-analysis. Significant associations were found between 31 SNPs and PCa. They
      were rs445114, rs620861, rs983085, rs1016343, rs1447295, rs1859962, rs2660753,
      rs2710646, rs2735839, rs3760511, rs4242382, rs4430796, rs4962416, rs5945572,
      rs5945619, rs6470494, rs6501455, rs6983267, rs6983561, rs7000448, rs7214479,
      rs7501939, rs7920517, rs7931342, rs9364554, rs9623117, rs10090154, rs10486567,
      rs10896449, rs10993994, and rs16901979. The weighted odds ratios for above SNPs
      ranged between 0.64 and 1.88 (all P < 0.05). Subgroup analysis further indicated
      that the significant associations of some SNPs existed only in specific ancestry
      population (P < 10-5). CONCLUSIONS: The current meta-analysis demonstrated the
      moderate effects of above 31 SNPs on PCa and 14 independent PCa risk loci were
      identified.

PMID- 20690140
TI  - Modeling of the human skull in EEG source analysis.
AB  - We used computer simulations to investigate finite element models of the layered
      structure of the human skull in EEG source analysis. Local models, where each
      skull location was modeled differently, and global models, where the skull was
      assumed to be homogeneous, were compared to a reference model, in which spongy
      and compact bone were explicitly accounted for. In both cases, isotropic and
      anisotropic conductivity assumptions were taken into account. We considered
      sources in the entire brain and determined errors both in the forward calculation
      and the reconstructed dipole position. Our results show that accounting for the
      local variations over the skull surface is important, whereas assuming isotropic
      or anisotropic skull conductivity has little influence. Moreover, we showed that,
      if using an isotropic and homogeneous skull model, the ratio between skin/brain
      and skull conductivities should be considerably lower than the commonly used
      80:1. For skull modeling, we recommend (1) Local models: if compact and spongy
      bone can be identified with sufficient accuracy (e.g., from MRI) and their
      conductivities can be assumed to be known (e.g., from measurements), one should
      model these explicitly by assigning each voxel to one of the two conductivities,
      (2) Global models: if the conditions of (1) are not met, one should model the
      skull as either homogeneous and isotropic, but with considerably higher skull
      conductivity than the usual 0.0042 S/m, or as homogeneous and anisotropic, but
      with higher radial skull conductivity than the usual 0.0042 S/m and a
      considerably lower radial:tangential conductivity anisotropy than the usual 1:10.

PMID- 20690141
TI  - Increased "default mode" activity in adolescents prenatally exposed to cocaine.
AB  - Prenatal cocaine exposure (PCE) is associated with attention/arousal
      dysregulation and possible inefficiencies in some cognitive functions. However,
      the neurobiological bases of these teratogenic effects have not been well
      characterized. Because activities in the default mode network (DMN) reflect
      intrinsic brain functions that are closely associated with arousal regulation and
      cognition, alterations in the DMN could underlie cognitive effects related to
      PCE. With resting-state and task activation functional magnetic resonance imaging
      (fMRI), this study investigated the possible PCE related changes in functional
      brain connectivity and brain activation in the DMN. In the resting state, the PCE
      group was found to have stronger functional connectivity in the DMN, as compared
      to the nonexposed controls. During a working memory task with emotional
      distracters, the PCE group exhibited less deactivation in the DMN and their fMRI
      signal was more increased by emotional arousal. These data revealed additional
      neural effects related to PCE, and consistent with previous findings, indicate
      that PCE may affect behavior and functioning by increasing baseline arousal and
      altering the excitatory/inhibitory balancing mechanisms involved in cognitive
      resource allocation.

PMID- 20690142
TI  - Inhibition of enzymatic browning in actual food systems by the Maillard reaction
      products.
AB  - BACKGROUND: The Maillard reaction occurring between amino acids and sugars
      produces neo-formed compounds having certain levels of antioxidant activity
      depending on the reaction conditions and the type of reactants. The objective of
      this study was to investigate enzymatic browning inhibition capacity of Maillard
      reaction products (MRPs) formed from different amino acids including arginine
      (Arg), histidine (His), lysine (Lys) and proline (Pro). RESULTS: The inhibitory
      effects of the MRPs on polyphenol oxidase (PPO) were determined. The total
      antioxidant capacity (TAC) of MRPs derived from different amino acids were in the
      order Arg > His > Lys > Pro. The TAC and PPO inhibition of MRPs were evaluated as
      a function of temperature (80-120  degrees C), time (1-6 h) and pH (2-12). Arg
      Glc and His-Glc MRPs exhibited strong TAC and PPO inhibition. Increasing
      temperature (up to 100  degrees C) and time also increased TAC and PPO
      inhibition. Kinetics analysis indicated a mixed type inhibition of PPO by MRPs.
      CONCLUSION: The results indicate that the MRPs derived from Arg and His under
      certain reaction conditions significantly prevent enzymatic browning in actual
      food systems. The intermediate compounds capable of preventing enzymatic browning
      are reductones and dehydroreductones, as confirmed by liquid chromatographic-mass
      spectrometric analyses.

PMID- 20690143
TI  - CENTS: cortical enhanced neonatal tissue segmentation.
AB  - The acquisition of high-quality magnetic resonance (MR) images of neonatal brains
      is largely hampered by their characteristically small head size and insufficient
      tissue contrast. As a result, subsequent image processing and analysis,
      especially brain tissue segmentation, are often affected. To overcome this
      problem, a dedicated phased array neonatal head coil is utilized to improve MR
      image quality by augmenting signal-to-noise ratio and spatial resolution without
      lengthening data acquisition time. In addition, a specialized hybrid atlas-based
      tissue segmentation algorithm is developed for the delineation of fine structures
      in the acquired neonatal brain MR images. The proposed tissue segmentation method
      first enhances the sheet-like cortical gray matter (GM) structures in the to-be
      segmented neonatal image with a Hessian filter for generation of a cortical GM
      confidence map. A neonatal population atlas is then generated by averaging the
      presegmented images of a population, weighted by their cortical GM similarity
      with respect to the to-be-segmented image. Finally, the neonatal population atlas
      is combined with the GM confidence map, and the resulting enhanced tissue
      probability maps for each tissue form a hybrid atlas is used for atlas-based
      segmentation. Various experiments are conducted to compare the segmentations of
      the proposed method with manual segmentation (on both images acquired with a
      dedicated phased array coil and a conventional volume coil), as well as with the
      segmentations of two population-atlas-based methods. Results show the proposed
      method is capable of segmenting the neonatal brain with the best accuracy, and
      also preserving the most structural details in the cortical regions.

PMID- 20690144
TI  - Effect of sialic acid content on glycoprotein pI analyzed by two-dimensional
      electrophoresis.
AB  - 2-DE is broadly used for quantitative analysis of differential protein expression
      in complex mixtures such as serum samples or cell lysates. PTMs directly
      influence the 2-DE pattern, and knowledge of the rules of protein separation is
      required in order to understand the protein distribution in a 2-DE gel.
      Glycosylation is the most common PTM and can modify both the molecular weight and
      the pI of a protein. In particular, the effect of charged monosaccharides (mainly
      sialic acids, SAs) on the 2-DE pattern of a protein is of major interest since
      changes in sialylation are regularly observed in comparative studies. Little is
      known about the pI shift of a glycoprotein induced by the presence of SAs, or
      whether this shift is the same for all glycoproteins. To address this issue, this
      study examined the influence of SA on the 2-DE pattern of three serum
      glycoproteins (haptoglobin, alpha1-antitrypsin and ribonuclease 1), which N
      glycan chains had been previously characterised, and reviewed existing
      bibliographic data. The SA content of the different glycoforms of a glycoprotein
      showed a negative linear correlation with the pI, although the slope varied among
      the studied glycoproteins. We also described a positive correlation between the
      protein pI and the pI decrease per SA molecule.

PMID- 20690145
TI  - Diagnostic criteria for apathy in clinical practice.
AB  - BACKGROUND: Apathy is an important and distressing behavioural symptom in
      Alzheimer's disease and in various neuropsychiatric disorders. Recently,
      diagnostic criteria for apathy have been proposed. OBJECTIVES: In groups of
      patients suffering from different neuropsychiatric diseases, (i) to estimate the
      prevalence of patients meeting the proposed diagnostic criteria; (ii) to estimate
      the concurrent validity of the criteria with the neuropsychiatric inventory (NPI)
      apathy item; (iii) to identify the most frequently met criteria or sub-criteria
      in each specific neuropsychiatric disease and (iv) to estimate the inter-observer
      reliability of the diagnostic criteria for apathy. METHODS: This cross-sectional,
      multicentric, observational study was performed on 306 patients. Each of the
      participating centres had to check the presence of apathy according to the
      diagnostic criteria for apathy in consecutive patients belonging to the following
      diagnoses list: Alzheimer disease (AD), mixed dementia, mild cognitive impairment
      (MCI), Parkinson's disease (PD), Schizophrenia (DSM-IV) and major depressive
      episode. In addition to the clinical interview, the assessment included the Mini
      Mental Score Examination (MMSE) and the NPI. At the end of the visit, clinicians
      were required to check the diagnostic criteria for apathy. RESULTS: Using the
      diagnostic criteria for apathy, the frequency of apathy was of 53% in the whole
      population, 55% in AD, 70% in mixed dementia, 43% in MCI, 27% in PD, 53% in
      schizophrenia and 94% in major depressive episode. In AD, mixed dementia, MCI and
      PD, the NPI apathy score was significantly higher for patient fulfilling the
      apathy criteria. Goal-directed cognitive activity (criteria B2-Cognition) was the
      most frequently observed domain followed by goal-directed behaviour (criteria B1
      Behaviour) and emotion (criteria B3), respectively. Inter-rater reliability was
      high for the overall diagnostic (kappa coefficient = 0.93; p = 0.0001) and for
      each criteria. CONCLUSION: This study is the first one to test the diagnostic
      criteria for apathy in clinical practice. Results make the diagnostic criteria
      useful for clinical practice and research.

PMID- 20690146
TI  - On-line separation of bacterial cells by carbon-electrode dielectrophoresis.
AB  - Dielectrophoresis (DEP) represents a powerful approach to manipulate and study
      living cells. Hitherto, several approaches have used 2-D DEP chips. With the aim
      to increase sample volume, in this study we used a 3-D carbon-electrode DEP chip
      to trap and release bacterial cells. A continuous flow was used to plug an
      Escherichia coli cell suspension first, to retain cells by positive DEP, and
      thereafter to recover them by washing with peptone water washing solution. This
      approach allows one not only to analyze DEP behavior of living cells within the
      chip, but also to further recover fractions containing DEP-trapped cells.
      Bacterial concentration and flow rate appeared as critical parameters influencing
      the separation capacity of the chip. Evidence is presented demonstrating that the
      setup developed in this study can be used to separate different types of
      bacterial cells.

PMID- 20690147
TI  - Global analysis of in vivo EGR1-binding sites in erythroleukemia cell using
      chromatin immunoprecipitation and massively parallel sequencing.
AB  - Early growth response gene 1 (EGR1) has been implicated in megakaryocyte
      differentiation induced by phorbol ester. But the molecule mechanism of EGR1 in
      this process has not been widely investigated. The identification of direct EGR1
      target genes in a global scale is critical for our understanding of how EGR1
      contributes to this process. In this study, we provide a global survey on the
      binding location of EGR1 in the K562 cells using chromatin immunoprecipitation
      and massively parallel sequencing. Over 14 000 highly confident in vivo EGR1
      binding sites were identified in phorbol 12-myristate 13-acetate-treated K562
      cells. More than 70% of these genomic sites associated with EGR1 binding were
      located around annotated gene regions. Molecular functional classification of
      6138 putative EGR1 target genes showed that the transcription factor class (695
      of 6138; 11%) is the largest significantly enriched one. The results showed that
      a high coverage of the genome and a high positive rate achieve were achieved.
      This whole genome study on the EGR1 targets may provide a better understanding of
      the EGR1 regulated genes and the downstream pathway in megakaryocyte
      differentiation.

PMID- 20690148
TI  - Unit cloning and amplification as novel and universal strategies for complex
      vector construction and small DNA fragment preparation.
AB  - With a novel and universal strategy for the cloning of multiple DNA fragments, a
      complex synthetic vector (pVEC100), harboring the target DNA fragments in
      conventional 100-bp DNA ladder, was constructed for efficient and large-scale
      production of 100-bp DNA marker through bacteria fermentation, plasmid extraction
      and restrictive digestion. Since the restrictive digestion of complex vectors
      yields insufficient small DNA fragments, an innovative PCR model was developed as
      an alternative. The PCR model comprised a specially designed template vector and
      a unit amplification model for producing groups of small DNA fragments. The unit
      amplification model improved the efficiency of the PCR protocol and made it more
      economical and easier for small DNA fragment amplification. The approach
      presented in this paper--a unit cloning model for constructing complex synthetic
      vectors combined with the modular design of unit amplification by PCR--is a
      powerful method for preparing small DNA fragments of DNA molecular weight
      standards.

PMID- 20690149
TI  - Electromigration diffusivity spectrometry: a way for simultaneous determination
      of diffusion coefficients from mixed samples.
AB  - A novel method was proposed for simultaneous measurement of diffusion
      coefficients, (D), from mixed samples by electrophoresis and termed
      electromigration-based diffusivity spectrometry. After theoretical treatment, D
      equation for practical use has been deduced. With a modified CE system built in
      laboratory, electromigration-based diffusivity spectrometry has been realized and
      validated to suit for fast and accurate determination of diffusivities of mixed
      aromatic amino acids, phenols and aromatic organic acid, giving diffusivity
      spectra by peak area versus D, much similar to mass spectra. The precision of the
      measurement was found to critically depend on pH value of running buffer, which
      should be so selected that the analytes and internal standards could be charged
      at above 0.5e. The standards have to be selected at an electric flux far from
      each other and from analytes. In these cases, sample and running buffer
      concentrations, voltage and system temperature were found to have only negligible
      impact on the determination. In our test, the obtained measuring precision was
      generally kept within 1% for five runs, and the measured values of D agreed well
      with those from literature, with a deviation of less than 2.2% after the right
      use of calibration standards.

PMID- 20690150
TI  - Determination of the binding constants of modafinil enantiomers with sulfated
      beta-cyclodextrin chiral selector by capillary electrophoresis using three
      different linear plotting methods.
AB  - Binding constants for the enantiomers of modafinil with the negatively charged
      chiral selector sulfated-beta-CD (S-beta-CD) using CE technique is presented. The
      calculations of the binding constants employing three different linearization
      plots (double reciprocal, X-reciprocal and Y-reciprocal) were performed from the
      electrophoretic mobility values of modafinil enantiomers at different
      concentrations of S-beta-CD in the BGE. The highest inclusion affinity of the
      modafinil enantiomers were observed for the S-enantiomer-S-beta-CD complex, in
      agreement with the computational calculations performed previously. Binding
      constants for each enantiomer-S-beta-CD complex at different temperatures, as
      well as thermodynamic parameters for binding, were calculated. Host-guest binding
      constants using the double reciprocal fit showed better linearity (r(2)>0.99) at
      all temperatures studied (15-30 degrees C) and compared with the other two fit
      methods. The linear van't Hoff (15-30 degrees C) plot obtained indicated that the
      thermodynamic parameters of complexation were temperature dependent for the
      enantiomers.

PMID- 20690151
TI  - Impurity profiling of dexamphetamine sulfate by cyclodextrin-modified
      microemulsion electrokinetic chromatography.
AB  - A CD-modified microemulsion electrokinetic chromatography method has been
      developed and validated for dexamphetamine sulfate which allows the simultaneous
      determination of charged and uncharged impurities of the drug including the
      levorotary (R)-enantiomer. The optimized background electrolyte consisted of 1.5%
      w/w SDS, 0.5% w/w ethyl acetate, 3.5% w/w 1-butanol, 2.5% w/w 2-propanol and 92%
      w/w 50 mM sodium phosphate buffer, pH 3.0, containing 5.5% w/w sulfated beta-CD.
      Separations were performed in a 50.2/40 cm, 50 MUm id fused silica capillary at a
      temperature of 20 degrees C and an applied voltage of -14 kV. Carbamazepine was
      used as internal standard. The assay was validated in the range of 0.1-1.0% for
      the related substances and 0.1-5.0% for levoamphetamine based on a concentration
      of 3 mg/mL of dexamphetamine sulfate. The LOD of all analytes ranged between 0.05
      and 0.2%. In commercial samples of dexamphetamine sulfate, levoamphetamine was
      found at concentrations between 3.2 and 3.8%, whereas none of the other
      impurities could be detected.

PMID- 20690153
TI  - Percutaneous closure of patent ductus arteriosus: a multiinstitutional registry
      comparing multiple devices.
AB  - BACKGROUND: There are no guidelines and multiple devices available now for
      closure of PDA. OBJECTIVE: We sought to determine which devices are used and
      their outcomes. METHODS: Prospectively collected data on closure of PDA at 12 US
      catheterization labs was entered into the MAGIC data registry between November
      2005 and September 2008. RESULTS: PDA closure was accomplished in 357 of 359
      attempted closures during the study period. Mean age, weight, and minimum ductal
      diameter were 4.3 +/- 6.8 years, 18.7 +/- 18.4 kg, and 2.1 +/- 1.4 mm,
      respectively. Devices used were Gianturco coils (161/359), Amplatzer Duct
      Occluder (ADO, 174/359), Flipper coils (18/359), and other devices (6/359).
      Gianturco coils had the least fluoroscopy and contrast exposure (8.7 +/- 7.5 min,
      P = 0.00001, 2.6 +/- 1.4 cm(3) kg(-1), P = 0.00001). Immediate angiographic
      success rates were 96.9% (156/161) for Gianturco coils, 89.7% (156/174) for the
      ADO, 100% (18/18) for Flipper coils, and 66.7% (4/6) for other devices. Major
      complication rates were 0.6% for Gianturco coils (1/161), 1.7% for ADO (3/174),
      and 83.3% for other devices (4/6). Minor complication rates by device were 1.9%
      for Gianturco coils (3/161), 2.3% for ADO (4/174), and 16.7% (1/6) for other
      devices. CONCLUSIONS: Gianturco coils, the ADO and Flipper coils were immediately
      successful with low complication profiles. The ADO and Gianturco coils were the
      predominate devices. The ADO was the device of choice for PDA > 3 mm with good
      success. In PDA < 3 mm, the Gianturco coil is as effective and safe as the ADO
      with less cost, less radiation, and less contrast exposure. (c) 2010 Wiley-Liss,
      Inc.

PMID- 20690152
TI  - Efficacy of everolimus eluting stent implantation in patients with calcified
      coronary culprit lesions: two-year angiographic and three-year clinical results
      from the SPIRIT II study.
AB  - BACKGROUND: Little is known about the impact of treatment with drug-eluting
      stents (DES) on calcified coronary lesions. This analysis sought to assess the
      safety and efficacy of the XIENCE V everolimus-eluting stent (EES) in patients
      with calcified or noncalcified culprit lesions. METHODS: The study population
      consisted of 212 patients with 247 lesions, who were treated with EES alone.
      Target lesions were angiographically classified as none/mild, moderate, or severe
      grades of calcification. The population was divided into two groups: those with
      at least one target lesion moderately or severely calcified (the calcified group:
      68 patients with 75 calcified lesions) and those with all target lesions having
      mild or no calcification (the noncalcified group: 144 patients). Six-month and 2
      year angiographic follow-up and clinical follow-up up to 3 years were completed.
      RESULTS: The baseline characteristics were not significantly different between
      both groups. When compared with the noncalcified group, the calcified group had
      significantly higher rates of 6-month in-stent angiographic binary restenosis
      (ABR, 4.3% vs. 0%, P = 0.03) and ischemia-driven target lesion revascularization
      (ID-TLR, 5.9% vs. 0%, P = 0.01), resulting in numerically higher major cardiac
      adverse events (MACE, 5.9% vs. 1.4%, P = 0.09). At 2 years, when compared with
      the noncalcified group, the calcified group presented higher in-stent ABR (7.4%
      vs. 0%, P = 0.08) and ID-TLR (7.8% vs. 1.5%, P = 0.03), resulting in numerically
      higher MACE (10.9% vs. 4.4%, P = 0.12). At 3 years, ID-TLR tended to be higher in
      the calcified group than in the noncalcified group (8.6% vs. 2.4%, P = 0.11),
      resulting in numerically higher MACE (12.1% vs. 4.7%, P = 0.12). CONCLUSIONS: The
      MACE rates in patients treated with EES for calcified lesions were higher than in
      those for noncalcified lesions, but remained lower than the results of previously
      reported stent studies. EES implantation in patients with calcified culprit
      lesions was safe and associated with favorable reduction of restenosis and repeat
      revascularization. (c) 2010 Wiley-Liss, Inc.

PMID- 20690154
TI  - Reduction in spasm with a long hydrophylic transradial sheath.
AB  - OBJECTIVES: We aimed to assess the efficiency of a long hydrophilic sheath in
      reducing radial spasm for transradial approach. BACKGROUND: Despite a lower
      access site complication rate, cardiac catheterization using transradial approach
      is not widely used. Radial spasm is one of the main issues for transradial
      angiography and percutaneous interventions. We assumed that radial artery
      protection using a long hydrophilic-coated sheath would reduce radial spasm
      compared to a bare short sheath. METHODS: Three hundred and fifty one patients
      (pts) admitted for transradial coronary angiography +/- percutaneous coronary
      interventions were randomly assigned to a long hydrophilic-coated or a short
      sheath (control group). Primary end point was the occurrence of a radial spasm
      defined by significant patient pain evaluated by scale score (>4) or significant
      catheter frictions during manipulation. Procedure failure, radial occlusion, and
      local complications were also assessed. RESULTS: Radial spasm was significantly
      reduced when using the long-coated compared to the short sheath in 7 (4%) vs. 32
      pts (18%) P < 0.001. No difference was found regarding procedure failure
      respectively 1.2% vs. 0.6%, local complication 0.6% vs. 1.2%, and radial
      occlusion 3.5% vs. 3.5%. CONCLUSION: Radial artery protection using the long
      hydrophilic-coated sheath was efficient in the prevention of radial spasm for
      transradial approach. (c) 2010 Wiley-Liss, Inc.

PMID- 20690156
TI  - Successful use of the five-in-six system with IVUS guided transradial renal
      artery stenting.
AB  - In transradial renal intervention, the long distance between the vascular access
      and the target lesion represents a major issue. The 100 cm guiding catheter (GC)
      may be too short to engage the renal artery particularly in tall patients or with
      excessive aortic turtousity. On the other hand, with the use of 125 cm long GC,
      only few premounted dedicated renal stents can be used. The shaft of the stent
      delivery system must be 140 cm or more to be compatible with the 125 GC. However,
      in many renal interventions, only few more centimeters are required to give the
      GC the sufficient working length needed for proper engagement and back up
      support. For this purpose, we used the Terumo "five-in-six" system to provide the
      necessary extra length through the protruding part of the 5 Fr GC out of the tip
      of the 6 Fr GC. With the super soft distal segment of the 5 FR GC deeply
      intubated into the right renal artery, we had the sufficient backup support to do
      renal stenting with IVUS guidance. This case illustrates that the "five-in-six"
      system can be an alternative strategy whenever extra length or strong backup
      support is needed during transradial renal artery intervention.

PMID- 20690157
TI  - Fragmentation pathways of metopimazine and its metabolite using ESI-MS(n), HR-MS
      and H/D exchange.
AB  - Metopimazine (MPZ) is a phenothiazine derivative used to prevent emesis during
      chemotherapy where few structural analysis of the aforementioned compound have
      been described in the literature. Thus, this work reports, for the first time,
      the detailed study of fragmentation pathways of MPZ and its metabolite (AMPZ)
      using electrospray ionization (EI) with multistage mass spectrometry (ESI-MS(n))
      in positive-ion mode. The structures of 21 product ions were identified and their
      accurate masses were determined using high resolution mass spectrometry (HRMS)
      experiments. Characteristic product ions of these two phenothiazine derivatives
      are more particularly displayed along with differences between their relative
      abundances and their structures checked by H/D exchange experiments.

PMID- 20690158
TI  - Determination of S-adenosyl-l-methionine in fruits by capillary electrophoresis.
AB  - INTRODUCTION: S-adenosyl-l-methionine (SAM) plays an important role in many
      biochemical reactions in plants. It is mainly used as a methyl donor for
      methylation reactions, but it also participates in, for example, the biosynthesis
      of polyamines and the plant hormone ethylene. OBJECTIVE: To develop a fast
      capillary electrophoresis technique to separate SAM in fruits and fruit juices
      without any pre-purification steps. METHODOLOGY: Four different extraction
      solutions and two extraction times were tested, of which 5% trichloroacetic acid
      (TCA) for 10 min was found most suited. A glycine : phosphate buffer (200 : 50
      mm, pH 2.5) was found optimal to analyse SAM in TCA extracts. Analyses were
      preformed on different climacteric and non-climacteric fruits and fruit juices.
      The calibration curve was created in degraded tomato extract. The CE-method was
      compared with a more conventional HPLC method described in literature. RESULTS:
      The CE technique made it possible to completely separate the S,S- and R,S
      diastereoisomeric forms of SAM. The CE method proved to be very fast (20 min
      total running time instead of 42 min) and more sensitive (limit of detection of
      0.5 um instead of 1 um) compared with the conventional HPLC method. CONCLUSION:
      Fast measurements of SAM in fruits and juices are favoured by capillary
      electrophoresis in a 200 : 50 mm glycine : phosphate (pH 2.5) buffer system.

PMID- 20690159
TI  - Investigation of ionic liquids under Bi-ion and Bi-cluster ions bombardment by
      ToF-SIMS.
AB  - A systematic study of five different imidazolium-based room temperature ionic
      liquids, 1-butyl-3-methylimidazolium acetate, 1-butyl-3-methylimidazolium
      nitrate, 1-butyl-3-methylimidazolium iodide, 1-butyl-3-methylimidazolium
      hexafluorophosphate and 1-butyl-3-methylimidazolium
      bis(trifluoromethylsulfonyl)imide were carried out by means of time-of-flight
      secondary ion mass spectrometry (ToF-SIMS) in positive and negative ion mode. The
      compounds were measured under Bi-ion and Bi-cluster ions (Bi(2-7)(+), Bi(3,
      5)(2+)) bombardment, and spectral information and general rules for the
      fragmentation pattern are presented. Evidence for hydrogen bonding, due to high
      molecular secondary cluster ions, could be found. Hydrogen bonding strength could
      be estimated by ToF-SIMS via correlation of the anionic yield enhancement with
      solvent parameters.

PMID- 20690160
TI  - Dynamic contrast-enhanced computed tomography for the quantification of tumor
      response to vasoactive agents in a rat tumor model: preliminary results.
AB  - RATIONALE AND OBJECTIVES: The purpose of this pilot study was to establish the
      ability of dynamic contrast enhanced computed tomography (DCE-CT) to detect
      changes in tumor blood flow (BF) and oxygenation induced by vasoactive substances
      in rats. MATERIALS AND METHODS: Under ultrasound guidance, a fiber-optic probe
      was guided into thigh tumors in eight rats and attached to an oxygenation/blood
      flow-sensing device. A DCE-CT sequence was acquired at the oxygen-sensing probe
      tip during injection of iodinated contrast media. Group 1 rats (n = 6) were
      administered a vasodilator (hydralazine, 5 mg/kg i.v.) and group 2 rats (n = 2)
      were given physiologic saline in a similar volume. DCE-CT was repeated at the
      probe tip after 30 min. BF in the whole tumor and at the probe tip were estimated
      pre- and post-drug administration and the percentage change was calculated.
      RESULTS: DCE-CT defined significant differences between pre- and post-drug BF in
      the whole tumor (p = 0.007) and at the probe tip (p = 0.03). Estimates of
      percentage change in BF in the whole tumor agreed with fiber-optic measure of
      percentage change perfusion (r(2)  = 0.60; p = 0.02) and pO(2) (r(2)  = 0.65; p =
      0.02). Estimates of percentage change in BF at the probe tip agreed with fiber
      optic measures of percentage change in perfusion (r(2)  = 0.83; p = 0.001) and
      pO(2) (r(2)  = 0.62; p = 0.02). CONCLUSIONS: Preliminary results indicate that
      DCE-CT is capable of identifying alterations in tumor BF in rats. The percentage
      change in BF agrees with a validated estimate of tumor perfusion and oxygenation.
      This research technique may prove useful for assessment of tumor BF during
      combined chemotherapeutic and radiation therapy to improve outcome.

PMID- 20690161
TI  - Mesenchymal stem cell labeling and in vitro MR characterization at 1.5 T of new
      SPIO contrast agent: Molday ION Rhodamine-BTM.
AB  - In vivo detection of transplanted stem cells is requisite for improving stem cell
      based treatments by developing a thorough understanding of their therapeutic
      mechanisms. MRI tracking of magnetically labeled cells is non-invasive and is
      suitable for longitudinal studies. Molday ION Rhodamine-BTM (MIRB) is a new
      superparamagnetic iron oxide (SPIO) contrast agent specifically formulated for
      cell labeling and is readily internalized by non-phagocytic cells. This
      investigation characterizes mesenchymal stem cell (MSC) labeling and MR imaging
      properties of this new SPIO agent. Effects of MIRB on MSC viability and
      differentiation as well as cellular loading properties were assessed for MSC
      labeled with MIRB at concentrations from 5 to 100 ug Fe/ml. Labeled MSC were
      evaluated, in vitro, on a clinical 1.5 T MRI. Optimal scanning sequences and
      imaging parameters were determined based on contrast-to-noise ratio and contrast
      modulation. Relaxation rates (1/T(2)*) for gradient-echo sequences were
      approximated and an idealized limit of detection was established. MIRB labeling
      did not affect MSC viability or the ability to differentiate into either bone or
      fat. Labeling efficiency was found to be approximately 95% for labeling
      concentrations at or above 20 ug Fe/ml. Average MIRB per MSC ranged from 0.7 pg
      Fe for labeling MIRB concentration of 5 ug Fe/ml and asymptotically approached a
      value of 20-25 pg Fe/MSC as labeling concentration increased to 100 ug Fe/ml. MRI
      analysis of MIRB MSC revealed long echo time, gradient echo sequences to provide
      the most sensitivity. Limit of detection for gradient echo sequences was
      determined to be less than 1000 MSC, with approximately 15 pg Fe/MSC (labeled at
      20 ug Fe/ml). These investigations have laid the groundwork and established
      feasibility for the use of this contrast agent for in vivo MRI detection of MSC.
      Properties evaluated in this study will be used as a reference for tracking
      labeled MSC for in vivo studies.

PMID- 20690162
TI  - Primary effusion lymphoma: genomic profiling revealed amplification of SELPLG and
      CORO1C encoding for proteins important for cell migration.
AB  - Primary effusion lymphoma (PEL) is associated with Kaposi sarcoma herpesvirus
      (KSHV) but its pathogenesis is poorly understood. Many KSHV-associated products
      can deregulate cellular pathways commonly targeted in cancer. However, KSHV
      infection alone is insufficient for malignant transformation. PEL also lacks the
      chromosomal translocations seen in other lymphoma subtypes. We investigated 28
      PELs and ten PEL cell lines by 1 Mb resolution array comparative genomic
      hybridization (CGH) and found frequent gains of 1q21-41 (47%), 4q28.3-35 (29%),
      7q (58%), 8q (63%), 11 (32%), 12 (61%), 17q (29%), 19p (34%), and 20q (34%), and
      losses of 4q (32%), 11q25 (29%), and 14q32 (63%). Recurrent focal amplification
      was seen at several regions on chromosomes 7, 8, and 12. High-resolution
      chromosome-specific tile-path array CGH confirmed these findings, and identified
      selectin-P ligand (SELPLG) and coronin-1C (CORO1C) as the targets of a cryptic
      amplification at 12q24.11. Interphase FISH and quantitative PCR showed
      SELPLG/CORO1C amplification (>4 extra copies) and low levels of copy number gain
      (1-4 extra copies) in 23% of PELs, respectively. Immunohistochemistry revealed
      strong expression of both SELPLG and coronin-1C in the majority of PELs,
      irrespective of their gene dosage. SELPLG is critical for cell migration and
      chemotaxis, while CORO1C regulates actin-dependent processes, thus important for
      cell motility. Their overexpression in PEL is expected to play an important role
      in its pathogenesis.

PMID- 20690163
TI  - Quercetin activates AMP-activated protein kinase by reducing PP2C expression
      protecting old mouse brain against high cholesterol-induced neurotoxicity.
AB  - It is known that a high-cholesterol diet induces oxidative stress, inflammatory
      response, and beta-amyloid (Abeta) accumulation in mouse brain, resulting in
      neurodegenerative changes. Quercetin, a naturally occurring flavonoid, has been
      reported to possess numerous biological activities beneficial to health. Our
      previous studies have demonstrated that quercetin protects mouse brain against D
      galactose-induced oxidative damage. Against this background, we evaluated the
      effect of quercetin on high-cholesterol-induced neurotoxicity in old mice and
      explored its potential mechanism. Our results showed that oral administration of
      quercetin significantly improved the behavioural performance of high-cholesterol
      fed old mice in both a step-through test and the Morris water maze task. This is
      at least in part caused by decreasing ROS and protein carbonyl levels and
      restoring Cu--Zn superoxide dismutase (Cu, Zn-SOD) activity. Furthermore,
      quercetin also significantly activated the AMP-activated protein kinase (AMPK)
      via down-regulation of protein phosphatase 2C (PP2C), which reduced the integral
      optical density (IOD) of activated microglia cells and CD11b expression, down
      regulated iNOS and cyclooxygenase-2 (COX-2) expression, and decreased IL-1beta,
      IL-6, and TNF-alpha expression in the brains of high-cholesterol-fed old mice
      through the suppression of NF-kappaB p65 nuclear translocation. Moreover, AMPK
      activation significantly increased 3-hydroxy-3-methylglutaryl-coenzyme A (HMG
      CoA) reductase and acetyl-CoA carboxylase (ACC) phosphorylation and reduced fatty
      acid synthase (FAS) expression in the brains of high-cholesterol-fed old mice,
      which reduced cholesterol levels, down-regulated cholesterol 24-hydroxylase
      (CYP46A1) and beta-amyloid converting enzyme 1 (BACE1) expression, decreased
      eukaryotic translation initiation factor 2alpha (eIF2alpha) phosphorylation, and
      lowered Abeta deposits. However, the neuroprotective effect of quercetin was
      weakened by intraperitoneal injection of compound C, an AMPK inhibitor. These
      results suggest that AMPK activated by quercetin may be a potential target to
      enhance the resistance of neurons to age-related diseases.

PMID- 20690164
TI  - PTR-TOF-MS and data-mining methods for rapid characterisation of agro-industrial
      samples: influence of milk storage conditions on the volatile compounds profile
      of Trentingrana cheese.
AB  - Proton transfer reaction-mass spectrometry (PTR-MS), a direct injection mass
      spectrometric technique based on an efficient implementation of chemical
      ionisation, allows for fast and high-sensitivity monitoring of volatile organic
      compounds (VOCs). The first implementations of PTR-MS, based on quadrupole mass
      analyzers (PTR-Quad-MS), provided only the nominal mass of the ions measured and
      thus little chemical information. To partially overcome these limitations and
      improve the analytical capability of this technique, the coupling of proton
      transfer reaction ionisation with a time-of-flight mass analyser has been
      recently realised and commercialised (PTR-TOF-MS). Here we discuss the very first
      application of this new instrument to agro-industrial problems and dairy science
      in particular. As a case study, we show here that the rapid PTR-TOF-MS
      fingerprinting coupled with data-mining methods can quickly verify whether the
      storage condition of the milk affects the final quality of cheese and we provide
      relevant examples of better compound identification in comparison with the
      previous PTR-MS implementations. In particular, 'Trentingrana' cheese produced by
      four different procedures for milk storage are compared both in the case of
      winter and summer production. It is indeed possible to set classification models
      with low prediction errors and to identify the chemical formula of the ion peaks
      used for classification, providing evidence of the role that this novel
      spectrometric technique can play for fundamental and applied agro-industrial
      themes.

PMID- 20690165
TI  - Phenilpropanoate identification in young wheat plants by liquid
      chromatography/tandem mass spectrometry: monomeric and dimeric compounds.
AB  - Metabolomic approach has become a very important tool for determining the actual
      gene expression and protein activity. Metabolism via the shikimate pathway in
      plant gives rise to a large number of aromatic compounds, including p
      hydroxycinnamates, which are mainly associated with their cell walls in complex
      structures, ester-linked to heteroxilans. In this work, ferulate dehydrodimers
      and related compounds were extracted from the cell walls of young lyophilized
      wheat plants with 2 mol/l NaOH for 4 h at 25  degrees C under N(2). After solid
      phase extraction, samples were analysed by high-performance liquid chromatography
      quadrupole-linear ion trap tandem mass spectrometry with the electrospray source
      operating in negative mode. Nineteen dehydrodiferulates, 2 hydrate forms, 3 oxo-
      forms, 2 decarboxilated forms and 1 dihydroxysinapate, were identified by mass
      spectra interpretation. In addition, five mixed dehydrodimers of ferulic-sinapic,
      ferulic-coumaric and ferulic-syringic acids were also identified. Reproducibility
      of peak areas was usually better than 10% but some minor components which may be
      procedural artefacts, although relatively mild conditions were used.

PMID- 20690166
TI  - A numerical coefficient for evaluation of the environmental impact of
      electromagnetic fields radiated by base stations for mobile communications.
AB  - The aim of this study is the development of an Electromagnetic Environmental
      Impact Factor (EEIF). This is a global parameter that represents the level of
      electromagnetic impact on a specific area due to the presence of radiating
      systems, such as base station (BS) antennas for mobile communications. The
      numerical value of the EEIF depends only on the electromagnetic field intensity,
      a well-defined physical quantity that can easily be measured or computed. The
      paper describes the significant parameters of the field distribution adopted to
      evaluate the EEIF, and the assumptions used to develop a proper scale of values.
      Finally, some examples of application of the EEIF method are analyzed for real
      situations in a typical urban area.

PMID- 20690167
TI  - Tourette's syndrome in adults.
AB  - Tourette's syndrome (TS) is defined as motor and phonic tics starting before age
      18 years, and therefore most studies have focused on childhood TS, whereas the
      disorder in adults has not been well characterized. We reviewed medical records
      of all new TS patients referred to our Movement Disorders Clinic over the past 5
      years, 19 years or older on initial evaluation and compared them with 100 TS
      patients 18 years or younger. The mean age at initial visit of 43 adult TS
      patients was 58.8 +/- 6.7 years, whereas the mean age at initial visit of
      children with TS was 12.9 +/- 2.0 years. Of the adult TS patients, 35 (81.4%) had
      a history of tics with onset before the age of 18 years (mean age at onset: 8.5
      +/- 3.4 years), with 8 (18.6%) reporting first occurrence of tics after the age
      of 18 years (mean age at onset: 37.8 +/- 13.2 years). Only two (4.7%) patients
      reported tic onset after the age of 50 years. Adult patients with TS had
      significantly more facial and truncal tics, and a greater prevalence of substance
      abuse and mood disorders, but fewer phonic tics, and lower rates of attention
      deficit hyperactivity disorder and oppositional behavior than children with TS.
      Adult TS largely represents reemergence or exacerbation of childhood-onset TS.
      During the course of TS, phonic and complex motor tics, self-injurious behaviors,
      and attention-deficit hyperactivity disorder tend to improve, but facial, neck,
      and trunk tics dominate the adult TS phenotype. In addition, adults with TS are
      more likely to exhibit substance abuse and mood disorders compared with children
      with TS.

PMID- 20690168
TI  - A cluster randomized controlled trial to determine the efficacy of Trauma Risk
      Management (TRiM) in a military population.
AB  - Trauma Risk Management is a peer-support program that aims to promote help
      seeking in the aftermath of traumatic events. Prior to its implementation, the
      British military conducted a randomized controlled trial of Trauma Risk
      Management against standard care in 12 warships; 6 were randomized to use Trauma
      Risk Management after collecting baseline measurements. Follow up after 12-18
      months found no significant change in psychological health or stigma scores in
      either group; however, the studied vessels only encountered low numbers of
      critical incidents. Additionally, measurements of organizational functioning were
      modestly better in the Trauma Risk Management ships. The authors conclude that
      within organizations using Trauma Risk Management may be beneficial and may, in
      time, lead to a valuable cultural shift.

PMID- 20690169
TI  - Long-term course of probable PTSD after the 9/11 attacks: a study in urban
      primary care.
AB  - Although the short- and midterm psychological effects of the attacks on September
      11, 2001 (9/11) have been well described, less is known about the long-term
      effects. This study examines the course of probable posttraumatic stress disorder
      (PTSD), its predictors and clinical consequences in a cohort of 455 primary care
      patients in New York City, interviewed approximately 1 and 4 years after 9/11.
      The rate of PTSD decreased from 9.6% to 4.1%. Pre-9/11 major depressive disorder
      emerged as the strongest predictor of PTSD, particularly late-PTSD. At follow-up,
      late-PTSD was associated with major depressive and anxiety disorders, and PTSD
      regardless of timing was associated with impaired functioning. Findings highlight
      the importance of ongoing evaluation of mental health needs in primary care
      settings in the aftermath of disasters.

PMID- 20690170
TI  - PTSD among a treatment sample of repeat DUI offenders.
AB  - Recent studies indicate that posttraumatic stress disorder (PTSD) is one of the
      most common psychiatric comorbidities among driving-under-the-influence (DUI)
      offenders in treatment. Investigation of DUI offenders' PTSD and clinical
      characteristics could have important implications for prevention and treatment.
      This prospective study examined the demographic and clinical characteristics of
      repeat DUI offenders with PTSD symptoms at baseline and 1-year follow-up. Seven
      hundred twenty-nine DUI offenders admitted to a 2-week inpatient program
      participated in the study. Participants with PTSD evidenced more severe
      psychiatric comorbidity and reported a higher DUI recidivism rate at 1-year than
      those without PTSD. This study suggests a need to address PTSD among DUI
      offenders, as well as to further develop methodologies for accurately reporting
      DUI recidivism.

PMID- 20690171
TI  - Defining torture: a review of 40 years of health science research.
AB  - The current review critically examines the body of torture research (N = 209),
      focusing on the definition and operationalization of the primary construct.
      Almost three-quarters (69.9%) of the studies reviewed did not reference any
      definition of torture. Few studies identified important contextual variables
      related to defining torture such as identities and motivations of perpetrators
      and severity of abuse. Definitional ambiguity further impacted how individuals
      were queried about their experiences and the extent to which torture was
      distinguished from other forms of maltreatment. Although there are notable
      exceptions, the methods used in the torture literature are variable and often
      undefined, impacting the interpretation of findings of risk factors,
      consequences, and treatment of torture events.

PMID- 20690172
TI  - Polybrominated diphenyl ethers (PBDEs) in Mediterranean mussels (Mytilus
      galloprovincialis) from selected Apulia coastal sites evaluated by GC-HRMS.
AB  - Samples of Mytilus galloprovincialis were examined to investigate the levels of
      polybrominated diphenyl ethers (PBDEs) in the Apulia's marine environment, a
      region in the South of Italy. The levels of nine PBDE congeners were measured in
      40 mussel samples taken from the aquaculture farms in the South of Adriatic Sea
      and North Ionian Sea along the Apulia coast. While accelerated solvent extraction
      (ASE) was the extraction technique adopted using acetone/n-hexane (1:1, v/v), the
      content of PBDEs was evaluated by using gas chromatography coupled with high
      resolution mass spectrometry (GC-HRMS) via electron ionization (EI) in the
      multiple ion monitoring (MIM) mode (two ions for each compound). The (13)C mass
      labeled compounds were used to establish the levels of PBDEs in M.
      galloprovincialis samples. The total concentration of PBDEs (SigmaPBDEs) ranged
      from 0.2 to 6.9 ng/g dry mass, with the highest concentrations found around
      coastal areas of Salento. With regard to the composition of PBDE congeners, BDE
      47, BDE-99 and BDE-100 were the predominant congeners in most of the samples. The
      present study is the first to report levels of PBDEs occurring in aquatic
      organisms living in aquaculture farms of Apulia region.

PMID- 20690173
TI  - Exploring the activity space of peptides binding to diverse SH3 domains using
      principal property descriptors derived from amino acid rotamers.
AB  - Although there were intensive works addressed on multivariate extraction of the
      informative components from numerous physicochemical parameters of amino acids in
      isolated state, the various conformational behaviors of amino acids in
      complicated biological context have long been underappreciated in the field of
      quantitative structure-activity relationship (QSAR). In this work, the amino acid
      rotamers, which were derived from statistical survey of protein crystal
      structures, were used to reproduce the conformational variety of amino acid side
      chains in real condition. In this procedure, these rotamers were superposed into
      a nx x ny x nz lattice and an artificial probe was employed to detect four kinds
      of nonbonding field potentials (i.e., electrostatic, steric, hydrophobic, and
      hydrogen bonds) at each lattice point using a Gaussian-type potential function;
      the generated massive data were then subjected to a principal component analysis
      (PCA) treatment to obtain a set of few, informative amino acid descriptors. We
      used this set of descriptors, that we named principal property descriptors
      derived from amino acid rotamers (PDAR), to characterize over 13,000 peptides
      with known binding affinities to 10 types of SH3 domains. Genetic algorithm/
      partial least square regression (GA/PLS) modeling and Monte Carlo cross
      validation (MCCV) demonstrated that the correlation between the PDAR descriptors
      and the binding affinities of peptides are comparable with or even better than
      previously published models. Furthermore, from the PDAR-based QSAR models we
      concluded that the core motif of peptides, particularly the electrostatic
      property, hydrophobicity, and hydrogen bond at residue positions P3, P2, and/or
      P0, contribute significantly to the hAmph SH3 domain-peptide binding, whereas two
      ends of the peptides, such as P6, P4, P-4, and P5, only play a secondary role in
      the binding.

PMID- 20690174
TI  - Highly porous titanium scaffolds for orthopaedic applications.
AB  - For many years, the solid metals and their alloys have been widely used for
      fabrication of the implants replacing hard human tissues or their functions. To
      improve fixation of solid implants to the surrounding bone tissues, the materials
      with porous structures have been introduced. By tissue ingrowing into a porous
      structure of metallic implant, the bonding between the implant and the bone has
      been obtained. Substantial pore interconnectivity, in metallic implants, allows
      extensive body fluid transport through the porous implant. This can provoke bone
      tissue ingrowth, consequently, leading to the development of highly porous
      metallic implants, which could be used as scaffolds in bone tissue engineering.
      The goal of this study was to develop and then investigate properties of highly
      porous titanium structures received from powder metallurgy process. The
      properties of porous titanium samples, such as microstructure, porosity, Young's
      modulus, strength, together with permeability and corrosion resistance were
      investigated. Porous titanium scaffolds with nonhomogeneous distribution of
      interconnected pores with pore size in the range up to 600 MUm in diameter and a
      total porosity in the range up to 75% were developed. The relatively high
      permeability was observed for samples with highest values of porosity. Comparing
      to cast titanium, the porous titanium was low resistant to corrosion. The
      mechanical parameters of the investigated samples were similar to those for
      cancellous bone. The development of high-porous titanium material shows high
      potential to be modern material for creating a 3D structure for bone regeneration
      and implant fixation.

PMID- 20690175
TI  - Use of micro-Raman spectroscopy to investigate hybrid layer quality in
      demineralized root dentine.
AB  - Treatment of early root caries using resin adhesives to stabilize demineralized
      dentine and deprive bacteria of nutrients is a recognized and conservative
      treatment option. Essential to its success is a stable resin-dentine interface,
      with effective infiltration of demineralized dentine and adequate resin curing.
      The objective of this study was therefore to examine degree of cure (DoC) and
      depth of penetration of dentine adhesives in demineralized dentine using micro
      Raman spectroscopy. Three commercially available adhesives were applied
      essentially according to manufacturers' instructions to visibly wet demineralized
      dentine, with two coats of primer to reduce dilution. Specimens were sectioned
      perpendicular to the bonded interface and micro-Raman spectroscopy performed on
      the cross section. Molecules associated with the adhesive were detected to depths
      greater than 100 MUm indicating a thicker hybrid layer than seen in sound
      dentine. The hybrid layer showed an increase in proportion of aliphatic C=C
      double bonds at the base of the hybrid layer, which may be a consequence of
      reduced DoC or phase separation. Micro-Raman spectra suggest deep zones contain
      an increased concentration of HEMA and a lower concentration of BisGMA, which is
      likely to be less stable and may contribute to early breakdown of the dentine
      adhesive interface.

PMID- 20690176
TI  - Effect of silica coating combined to a MDP-based primer on the resin bond to Y
      TZP ceramic.
AB  - The aim of this study was to evaluate the influence of silica coating and 10
      methacryloyloxydecyl dihydrogen phosphate (MDP)-based primer applications upon
      the bonding durability of a MDP-based resin cement to a yttrium stabilized
      tetragonal zirconia (Y-TZP) ceramic. Ninety-six Y-TZP tabs were embedded in an
      acrylic resin (free surface for adhesion: 5 * 5 mm(2)), ground finished and
      randomly divided into four groups (N = 24) according to the ceramic surface
      conditioning: (1) cleaning with isopropanol (ALC); (2) ALC + phosphoric acid
      etching + MDP-based primer application (MDP-primer); (3) silica coating + 3
      methacryloyloxypropyl trimethoxysilane (MPS)-based coupling agent application
      (SiO2 + MPS-Sil); and (4) SiO2 + MDP-primer. The MDP-based resin cement was
      applied on the treated surface using a cylindrical mold (diameter= 3 mm). Half of
      the specimens from each surface conditioning were stored in distilled water (37 
      degrees C, 24 h) before testing. Another half of the specimens were stored (90
      days) and thermo-cycled (12,000 x) during this period (90 d/TC) before testing. A
      shear bond strength (SBS) test was performed at a crosshead speed of 0.5 mm/min.
      Two factors composed the experimental design: ceramic conditioning strategy (in
      four levels) and storage condition (in two levels), totaling eight groups. After
      90 d/TC (Tukey; p < 0.05), SiO2 + MDP-primer (24.40 MPa) promoted the highest
      SBS. The ALC and MDP-primer groups debonded spontaneously during 90 d/TC. Bonding
      values were higher and more stable in the SiO2 groups. The use of MDP-primer
      after silica coating increased the bond strength.

PMID- 20690177
TI  - Innate, antigen-independent role for T cells in the activation of the immune
      system by Propionibacterium acnes.
AB  - Propionibacterium acnes is a human commensal but also an opportunistic pathogen.
      In mice, P. acnes exerts strong immunomodulatory activities, including formation
      of intrahepatic granulomas and induction of LPS hypersensitivity. These
      activities are dependent on P. acnes recognition via TLR9 and subsequent IL-12
      mediated IFN-gamma production. We show that P. acnes elicits IL-12p40 and p35
      mRNA expression in macrophages, and IFN-gamma mRNA in liver CD4(+) T cells and NK
      cells. After priming with P. acnes, CD4(+) T cells serve as the major IFN-gamma
      mRNA source. In the absence of CD4(+) T cells, CD8(+) T cells (regardless of
      antigenic specificity) or NK cells can produce sufficient IFN-gamma to induce the
      P. acnes-driven immune effects. Moreover, in the absence of alpha beta T cells,
      gamma delta T cells also enable the development of strongly enhanced TNF-alpha
      and IFN-gamma responses to LPS and intrahepatic granuloma formation. Thus, under
      microbial pressure, different T-cell types, independent of their antigen
      specificity, exert NK-cell-like functions, which contribute decisively to the
      activation of the innate immune system.

PMID- 20690178
TI  - Retinoic acid-induced gut tropism improves the protective capacity of Treg in
      acute but not in chronic gut inflammation.
AB  - Treg are endowed with immunosuppressive activities and have been proposed as
      promising targets for the therapy of autoimmune diseases. As the suppressive
      capacity of Treg depends on their migration into the affected tissues, we tested
      here whether modulation of Treg homing would enhance their capacity to suppress
      inflammation in mouse models of inflammatory bowel disease. Retinoic acid (RA)
      was used to induce the gut-specific homing receptor alpha(4)beta(7) efficiently
      and, to some extent, the chemokine receptor CCR9 on in vitro expanded Treg. Upon
      transfer, RA-treated Treg were indeed more potent suppressors in an acute, small
      intestinal inflammation model, compared with Treg stimulated without RA. By
      contrast, the efficacy of Treg to resolve an established, chronic inflammation of
      the colon in the transfer colitis model was not affected by RA-treatment. In the
      latter model, a rapid loss of RA-induced alpha(4)beta(7) expression and de novo
      induction of alpha(4)beta(7) on previously negative cells was observed on
      transferred Treg, which implies that Treg acquire gut-seeking properties in vivo
      under inflammatory and/or lymphopenic conditions. Together, our data show that
      the induction of appropriate homing properties prior to transfer increases the
      protective potential of adoptively transferred Treg in acute, but not in chronic,
      inflammatory disorders of the gut.

PMID- 20690179
TI  - Allergen-specific naive and memory CD4+ T cells exhibit functional and phenotypic
      differences between individuals with or without allergy.
AB  - Although allergen-specific CD4(+) T cells are detectable in the peripheral blood
      of both individuals with or without allergy, their frequencies and phenotypes
      within the memory as well as naive repertoires are incompletely known. Here, we
      analyzed the DRB1*0401-restricted responses of peripheral blood-derived memory
      (CD4(+)CD45RO(+)) and naive (CD4(+)CD45RA(+)) T cells from subjects with or
      without allergy against the immunodominant epitope of the major cow dander
      allergen Bos d 2 by HLA class II tetramers in vitro. The frequency of Bos d 2(127
      142)-specific memory T cells in the peripheral blood-derived cultures appeared to
      be higher in subjects with allergy than those without, whereas naive Bos d 2(127
      142)-specific T cells were detectable in the cultures of both groups at nearly
      the same frequency. Surprisingly, the TCR avidity of Bos d 2(127-142)-specific T
      cells of naive origin, as assessed by the intensity of HLA class II tetramer
      staining, was found to be higher in individuals with allergy. Upon restimulation,
      long-term Bos d 2(127-142)-specific T-cell lines generated from both memory and
      naive T-cell pools from individuals with allergy proliferated more strongly,
      produced more IL-4 and IL-10, and expressed higher levels of CD25 but lower
      levels of CXCR3 than the T-cell lines from individuals without allergy,
      demonstrating differences also at the functional level. Collectively, our current
      results suggest that not only the memory but also the naive allergen-specific T
      cell repertoires differ between individuals with or without allergy.

PMID- 20690180
TI  - Commensal microflora and interferon-gamma promote steady-state interleukin-7
      production in vivo.
AB  - IL-7 is a major regulator of lymphocyte homeostasis; however, little is known
      about the mechanisms that regulate IL-7 production. To study Il7 gene regulation
      in vivo, we generated a novel IL-7-reporter mouse, which allows the non-invasive
      quantification of Il7 gene activity in live mice and, additionally, the
      simultaneous activation/inactivation of target genes in IL-7-producing cells.
      With these IL-7-reporter mice, we identify thymus, skin and intestine as major
      sources of IL-7 in vivo. Importantly, we show that IFN-gamma and the commensal
      microflora promote steady-state IL-7 production in the intestine. Furthermore, we
      demonstrate that the blockade of IFN-gamma signaling in intestinal epithelial
      cells strongly reduces their IFN-gamma-driven IL-7 production. In summary, our
      data suggest a feedback loop in which commensal bacteria drive IFN-gamma
      production by lymphocytes, which in turn promotes epithelial cell IL-7 production
      and the survival of IL-7-dependent lymphocytes.

PMID- 20690181
TI  - Fixing an irrelevant TCR alpha chain reveals the importance of TCR beta diversity
      for optimal TCR alpha beta pairing and function of virus-specific CD8+ T cells.
AB  - TCR repertoire diversity can influence the efficacy of CD8(+) T-cell populations,
      with greater breadth eliciting better protection. We analyzed TCR beta diversity
      and functional capacity for influenza-specific CD8(+) T cells expressing a single
      TCR alpha chain. Mice (A7) transgenic for the H2K(b)OVA(257-264)-specific V alpha
      2.7 TCR were challenged with influenza to determine how fixing this "irrelevant"
      TCR alpha affects the "public" and restricted D(b)NP(366) (+)CD8(+) versus the
      "private" and diverse D(b)PA(224) (+)CD8(+) responses. Though both D(b)NP(366)
      (+)CD8(+) and D(b)PA(224) (+)CD8(+) sets are generated in virus-primed A7 mice,
      the constrained D(b)NP(366) (+)CD8(+) population lacked the characteristic,
      public TCRV beta 8.3, and consequently was reduced in magnitude and pMHC-I
      avidity. For the more diverse D(b)PA(224) (+)CD8(+) T cells, this particular
      forcing led to a narrowing and higher TCR beta conservation of the dominant V
      beta 7, though the responses were of comparable magnitude to C57BL/6J controls.
      Interestingly, although both the TCR beta diversity and the cytokine profiles
      were reduced for the D(b)NP(366) (+)CD8(+) and D(b)PA(224) (+)CD8(+) sets in
      spleen, the latter measure of polyfunctionality was comparable for T cells
      recovered from the infected lungs of A7 and control mice. Even "sub-optimal" TCR
      alpha beta pairs can operate effectively when exposed in a milieu of high virus
      load. Thus, TCR beta diversity is important for optimal TCR alpha beta pairing
      and function when TCR alpha is limiting.

PMID- 20690182
TI  - Increased CD127 expression on activated FOXP3+CD4+ regulatory T cells.
AB  - Regulatory T cells (Treg) are commonly identified by CD25 (IL-2R alpha) surface
      expression and/or intracellular expression of the FOXP3 transcription factor. In
      addition, Treg are also characterized by low CD127 (IL-7R alpha) expression when
      compared to conventional T cells and their biology in the periphery is considered
      essentially independent of IL-7. We further investigated CD127 expression on Treg
      and we demonstrated differential CD127 expression depending on Treg subsets
      considered. Notably, we observed high CD127 expression on inducible costimulatory
      molecule (ICOS)- and CD103-expressing Treg subsets. Since these two markers
      reflect activation status, we addressed whether Treg activation modulated CD127
      expression. We demonstrated that in contrast to conventional T cells, Treg
      significantly upregulated CD127 expression during in vitro and in vivo activation
      using adoptive transfer and contact dermatitis models. High CD127 expression on
      Treg was also predominantly detected ex vivo in some specific sites, notably bone
      marrow and skin. Importantly, higher CD127 expression on Treg correlated with
      higher phosphorylation of STAT5 upon IL-7 exposure. High CD127 expression on Treg
      also provided survival advantage upon in vitro incubation with IL-7. We thus
      demonstrated that low CD127 expression is not an intrinsic characteristic of Treg
      and we identified activated Treg as a potential target of endogenous or
      therapeutic IL-7.

PMID- 20690183
TI  - Role of hemorrhage in the induction of systemic inflammation and remote organ
      damage: analysis of combined pseudo-fracture and hemorrhagic shock.
AB  - This study was performed to analyze the role of hemorrhage-induced hypotension in
      the induction of systemic inflammation and remote organ dysfunction. Male C57/BL6
      mice (6- to 10-week old and 20-30 g) were used. Animals were either subjected to
      pseudo-fracture [PF; standardized soft-tissue injury and injection of crushed
      bone, PF group: n = 9], or PF combined with hemorrhagic shock (HS + PF group: n =
      6). Endpoint was 6 h. Systemic inflammation was assessed by IL-6 and IL-10
      levels. Myeloperoxidase (MPO) and NF-kappaB activity in the lung and liver tissue
      were obtained to assess remote organ damage. The increases of systemic cytokines
      are similar for animals subjected to PF and PF + HS (IL-6: 189 pg/ml +/- 32.5 vs.
      160 pg/ml +/- 5.3; IL-10: 60.3 pg/ml +/- 15.8 vs. 88 pg/ml +/- 32.4).
      Furthermore, the features (ALT; NF-kappaB) of liver injury are equally elevated
      in mice subjected to PF (76.9 U/L +/- 4.5) and HS + PF (80 U/L +/- 5.5). Lung
      injury, addressed by MPO activity was more severe in group HS + PF (2.95 ng/ml +/
      0.32) than in group PF (1.21 ng/ml +/- 0.2). Both PF and additional HS cause a
      systemic inflammatory response. In addition, hemorrhage seems to be associated
      with remote affects on the lung.

PMID- 20690184
TI  - Intracellular tension in periosteum/perichondrium cells regulates long bone
      growth.
AB  - Perichondrium/periosteum is involved in regulating long bone growth. Long bones
      grow faster after removal or circumferential division of periosteum. This can be
      countered by culturing them in conditioned medium from perichondrium/periosteum
      cells. Because both complete removal and circumferential division are effective,
      we hypothesized that perichondrium/periosteum cells require an intact environment
      to release the appropriate soluble factors. More specifically, we propose that
      this release depends on their ability to generate intracellular tension. This
      hypothesis was explored by modulating the ability of perichondrium/periosteum
      cells to generate intracellular tension and monitoring the effect thereof on long
      bone growth. Perichondrium/periosteum cells were cultured on substrates with
      different stiffness. The medium produced by these cultures was added to embryonic
      chick tibiotarsi from which perichondrium/periosteum was either stripped or left
      intact. After 3 culture days, long bone growth was proportionally related to the
      stiffness of the substrate on which perichondrium/periosteum cells were grown
      while they produced conditioned medium. A second set of experiments demonstrated
      that the effect occurred through expression of a growth-inhibiting factor, rather
      than through the reduction of a stimulatory factor. Finally, evidence for the
      importance of intracellular tension was obtained by showing that the inhibitory
      effect was abolished when perichondrium/periosteum cells were treated with
      cytochalasin D, which disrupts the actin microfilaments. Thus, we concluded that
      modulation of long bone growth occurs through release of soluble inhibitors by
      perichondrium/periosteum cells, and that the ability of cells to develop
      intracellular tension through their actin microfilaments is at the base of this
      mechano-regulated control pathway.

PMID- 20690185
TI  - Interleukin-1beta induces angiogenesis and innervation in human intervertebral
      disc degeneration.
AB  - Degenerative disorders of the intervertebral discs (IVDs) are generally
      characterized by enhanced matrix degradation, angiogenesis, innervation, and
      increased expression of catabolic cytokines. In this study, we investigated the
      effects of inflammatory cytokines, IL-1beta, and TNF-alpha, on the expression of
      an angiogenic factor, vascular endothelial growth factor (VEGF), and neurotrophic
      factors, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF),
      in human IVD degeneration. IL-1beta and TNF-alpha stimulated the gene expression
      of VEGF, NGF, and BDNF in nucleus pulposus (NP) cells isolated from patient
      tissues. Immunohistochemical results demonstrated a positive correlation between
      IL-1beta and VEGF/NGF/BDNF expression in human IVD tissues. RNA expression
      analysis of patient tissues also identified positive correlations between VEGF
      and platelet endothelial cell adhesion molecule-1 (PECAM-1) and between NGF/BDNF
      and protein gene product 9.5 (PGP9.5). Our findings suggest that IL-1beta is
      generated during IVD degeneration, which stimulates the expression of VEGF, NGF,
      and BDNF, resulting in angiogenesis and innervation.

PMID- 20690186
TI  - Tumor necrosis factor-alpha antagonist administration recovers skeletal muscle
      dysfunction in ovariectomized rats.
AB  - Skeletal muscles deteriorate after ovariectomy. Molecular pathway of this
      deterioration has not been defined. Tumor necrosis factor (TNF)-alpha activation
      is assumed to trigger muscle atrophy and administration of its antagonist is
      hypothesized to recover this atrophy in rats. Slow-twitch soleus and fast-twitch
      extensor digitorum longus muscle functions were investigated in intact,
      ovariectomized (OVX), and OVX plus 10 ug/g/week TNF-alpha antagonist administered
      female rats. Maximum isometric twitch and tetanic contraction responses were
      lower in the OVX groups. Maximum isometric twitch amplitudes recovered in the
      extensor digitorum longus but not in the soleus muscles after TNF-alpha
      antagonist administration. The decrease in responses to tetanic stimulations
      recovered in the OVX-TNF group at frequencies higher than 20 Hz in both muscle
      types. OVX animals body weight was 21% higher than intact animals. Muscle weight
      to body weight ratios of the OVX groups were higher than the control group which
      recovered after TNF-alpha antagonist administration. Findings suggest that the
      functional loss in OVX rat muscles is TNF-alpha pathway dependent. Skeletal
      muscle atrophy and function after OVX recovered by TNF-alpha antagonist
      administration.

PMID- 20690187
TI  - Solubility and bioavailability of stabilized amorphous calcium carbonate.
AB  - Since its role in the prevention of osteoporosis in humans was proven some 30
      years ago, calcium bioavailability has been the subject of numerous scientific
      studies. Recent technology allowing the production of a stable amorphous calcium
      carbonate (ACC) now enables a bioavailability analysis of this unique form of
      calcium. This study thus compares the solubility and fractional absorption of
      ACC, ACC with chitosan (ACC-C), and crystalline calcium carbonate (CCC).
      Solubility was evaluated by dissolving these preparations in dilute phosphoric
      acid. The results demonstrated that both ACC and ACC-C are more soluble than CCC.
      Fractional absorption was evaluated by intrinsically labeling calcium carbonate
      preparations with (45)Ca, orally administrated to rats using gelatin capsules.
      Fractional absorption was determined by evaluating the percentage of the
      administrated radioactive dose per milliliter that was measured in the serum,
      calcium absorption in the femur, and whole-body retention over a 34-hour period.
      Calcium serum analysis revealed that calcium absorption from ACC and ACC-C
      preparations was up to 40% higher than from CCC, whereas retention of ACC and ACC
      C was up to 26.5% higher than CCC. Absorbed calcium in the femurs of ACC
      administrated rats was 30% higher than in CCC-treated animals, whereas 15% more
      calcium was absorbed following ACC-C treatment than following CCC treatment. This
      study demonstrates the enhanced solubility and bioavailability of ACC over CCC.
      The use of stable ACC as a highly bioavailable dietary source for calcium is
      proposed based on the findings of this study.

PMID- 20690188
TI  - Local reaction kinetics by imaging: CO oxidation on polycrystalline platinum.

PMID- 20690189
TI  - Effects of an educational program and a standardized insulin order form on
      glycemic outcomes in non-critically ill hospitalized patients.
AB  - BACKGROUND: The optimal approach to managing hyperglycemia in noncritically ill
      hospital patients is unclear. OBJECTIVE: To investigate the effects of targeted
      quality improvement interventions on insulin prescribing and glycemic control.
      DESIGN: A cohort study comparing an intervention group (IG) to a concurrent
      control group (CCG) and an historic control group (HCG). SETTING: University of
      Michigan Hospital. PATIENTS: Hyperglycemic, noncritically ill hospital patients
      treated with insulin. INTERVENTION: Physician and nurse education and a
      standardized insulin order form based on the principles of physiologic insulin
      use. MEASUREMENTS: Glycemic control and insulin prescribing patterns. RESULTS:
      Patients in the IG were more likely to be treated with a combination of scheduled
      basal and nutritional insulin than in the other groups. In the final adjusted
      regression model, patients in the IG were more likely to be in the target glucose
      range (odds ratio [OR], 1.72; P = 0.01) and less likely to be severely
      hyperglycemic (OR, 0.65; P < 0.01) when compared to those in the CCG. Patients in
      the IG were also less likely to experience hypoglycemia than those in the CCG (P
      = 0.06) or the HCG (P = 0.01). Over 80% of all patient-days for all groups
      contained glucose readings outside of the target range. CONCLUSIONS: Standardized
      interventions encouraging the physiologic use of subcutaneous insulin can lead to
      significant improvements in glycemic control and patient safety in hospitalized
      patients. However, the observed improvements are modest, and poor metabolic
      control remains common, despite these interventions. Additional research is
      needed to determine the best strategy for safely achieving metabolic control in
      these patients.

PMID- 20690190
TI  - The use of smartphones for clinical communication on internal medicine wards.
AB  - BACKGROUND: Communication between clinicians is hampered by the frequent
      difficulty in reaching the most responsible physician for a patient as well as
      the use of outdated methods such as numeric paging. The aim of this study was to
      evaluate the use of smartphones to improve communication on internal medicine
      wards. METHOD: At the Toronto General Hospital, residents were provided with
      smartphones. To simplify reaching the most responsible resident for a patient, a
      smartphone designated as "Team BlackBerry" was also carried by each senior
      resident and then passed to the resident covering the team at night and on
      weekends. Nurses were able to send email messages or call smartphones directly.
      RESULTS: There were on average of 9.1 incoming calls, 6.6 outgoing calls, 14.3
      received emails, and 2.8 sent emails per day to each Team BlackBerry. Team
      BlackBerrys received up to 35 calls and 57 emails per day. Residents strongly
      preferred the smartphones over conventional paging with perceived improvements in
      all items measured and felt that it improved efficiency and communication.
      Although nurses perceived a reduction in the time required to contact a physician
      (27.6 vs. 11 minutes P < 0.001), their overall satisfaction with physician's
      response time for urgent issues did not improve significantly. DISCUSSION: When
      smartphones were used for clinical communication, residents perceived an
      improvement in communication with them. Residents strongly preferred emails as
      opposed to telephone calls as the prime method of communication. Further
      objective evaluation is necessary to determine if this intervention improves
      efficiency and more importantly, quality of care.

PMID- 20690191
TI  - Role and cellular source of nicotinamide adenine dinucleotide phosphate oxidase
      in hepatic fibrosis.
AB  - Reactive oxygen species (ROS) generated by nicotinamide adenine dinucleotide
      phosphate oxidase (NOX) is required for liver fibrosis. This study investigates
      the role of NOX in ROS production and the differential contribution of NOX from
      bone marrow (BM)-derived and non-BM-derived liver cells. Hepatic fibrosis was
      induced by bile duct ligation (BDL) for 21 days or by methionine-choline
      deficient (MCD) diet for 10 weeks in wild-type (WT) mice and mice deficient in
      p47phox (p47phox knockout [KO]), a component of NOX. The p47phox KO chimeric mice
      were generated by the combination of liposomal clodronate injection, irradiation,
      and BM transplantation of p47phox KO BM into WT recipients and vice versa. Upon
      BDL, chimeric mice with p47phox KO BM-derived cells, including Kupffer cells, and
      WT endogenous liver cells showed a ~25% reduction of fibrosis, whereas chimeric
      mice with WT BM-derived cells and p47phox KO endogenous liver cells, including
      hepatic stellate cells, showed a ~60% reduction of fibrosis. In addition, p47phox
      KO compared to WT mice treated with an MCD diet showed no significant changes in
      steatosis and hepatocellular injury, but a ~50% reduction in fibrosis. Cultured
      WT and p47phox KO hepatocytes treated with free fatty acids had a similar
      increase in lipid accumulation. Free fatty acids promoted a 1.5-fold increase in
      ROS production both in p47phox KO and in WT hepatocytes. CONCLUSION: NOX in both
      BM-derived and non-BM-derived cells contributes to liver fibrosis. NOX does not
      play a role in experimental steatosis and the generation of ROS in hepatocytes,
      but exerts a key role in fibrosis.

PMID- 20690193
TI  - Implementation of a screen and treat program for child posttraumatic stress
      disorder in a school setting after a school suicide.
AB  - To provide effective treatments for childhood posttraumatic stress disorder
      (PTSD) children with PTSD must first be identified. The authors implemented a
      "screen and treat" program following a widely witnessed school suicide. Three
      months after the suicide, exposed students received the Child Trauma Symptom
      Questionnaire at school. Parents received the questionnaire to rate their
      children's PTSD symptoms. Children with scores > or =5 received follow-up
      interviews and those diagnosed with PTSD were referred for treatment. Ninety-six
      percent of exposed students were screened, 14% screened positive, and 6% had
      PTSD. Child and parent agreement was generally poor. All children with PTSD were
      successfully referred to treatment. Screen and treat programs using existing
      clinical instruments are efficient and acceptable for use in school settings
      following trauma.

PMID- 20690192
TI  - Associations between serum lipids and hepatitis C antiviral treatment efficacy.
AB  - Approximately one half of patients who undergo antiviral therapy for chronic
      hepatitis C virus (HCV) genotype 1 infection do not respond to treatment. African
      Americans (AAs) are less responsive to treatment than Caucasian Americans (CAs),
      but the reasons for this disparity are largely unknown. Recent studies suggest
      that serum lipids may be associated with treatment response. The aims of this
      study were to evaluate baseline and changes in serum lipids during therapy,
      determine whether serum lipids are associated with virological response, and
      assess whether these measures explain the racial difference in efficacy. The
      study participants were from Virahep-C, a prospective study of treatment-naive
      patients with genotype 1 HCV infection who received peginterferon (PEG-IN) alfa
      2a plus ribavirin therapy for up to 48 weeks. Fasting serum lipids were analyzed
      at baseline and during and after therapy in 160 AAs and 170 CAs. A relative risk
      (RR) model was employed to evaluate characteristics associated with sustained
      virological response (SVR). Antiviral therapy was associated with changes in
      serum lipids during and after antiviral therapy, with the changes differing by
      race and the amount of PEG-IFN taken. Baseline lipid measures independently
      associated with higher rates of SVR were lower triglyceride and higher low
      density lipoprotein cholesterol, with an interaction between high-density
      lipoprotein cholesterol (HDLc) and gender. Lipid measures did not contribute
      significantly to an explanation of the racial difference in SVR. CONCLUSION:
      Serum lipids are associated with SVR, although these paramaters did not explain
      the racial difference in treatment response. The results of this study are
      compatible with proposed biological mechanisms of HCV entry, replication, and
      secretion, and may underscore new potential therapeutic targets for HCV
      eradication.

PMID- 20690194
TI  - Trauma centrality and PTSD in veterans returning from Iraq and Afghanistan.
AB  - Research has demonstrated that the extent to which an individual integrates a
      traumatic event into their identity ("trauma centrality") positively correlates
      with posttraumatic stress disorder (PTSD) symptom severity. No research to date
      has examined trauma centrality in individuals exposed to combat stress. This
      study investigated trauma centrality using the abridged Centrality of Event Scale
      (Berntsen & Rubin, 2006) among Operation Enduring Freedom/Operation Iraqi Freedom
      combat veterans (n = 46). Multiple regression analyses demonstrated that trauma
      centrality predicted PTSD symptoms. Trauma centrality and PTSD symptoms remained
      significantly correlated when controlling for depression in subgroups of veterans
      with or without probable PTSD. This study replicates and extends findings that
      placing trauma at the center of one's identity is associated with PTSD
      symptomatology.

PMID- 20690195
TI  - Elder mistreatment and physical health among older adults: the South Carolina
      Elder Mistreatment Study.
AB  - Exposure to potentially traumatic events (PTEs), including interpersonal
      violence, is associated with poorer physical health in young adults. This
      relation has not been well-investigated among older adults in specific
      populations. The present study was designed to investigate whether exposure to
      PTEs and elder mistreatment are associated with physical health status among
      older adults residing in South Carolina. Older adults aged 60 and above (N = 902)
      participated in a structured interview assessing elder mistreatment history,
      PTEs, demographics, and social dependency variables. Results demonstrated that
      PTEs were associated with poor self-rated health independently and when
      controlling for other significant predictors. A recent history of emotional
      mistreatment was associated with poor self-rated health independently, but not
      when controlling for other significant predictors.

PMID- 20690196
TI  - Posttraumatic growth in exposure therapy for PTSD.
AB  - This study aims to increase our understanding of trauma positive outcomes by (a)
      exploring associations between posttraumatic growth and posttraumatic stress
      disorder (PTSD), and (b) investigating posttraumatic growth course and its impact
      on exposure treatment. In 80 mixed trauma PTSD patients, growth was negatively
      related to PTSD symptoms, especially emotional numbing. Sixty-five PTSD patients
      also completed Prolonged Exposure therapy with pretreatment and posttreatment
      assessments. Posttraumatic growth-New Possibilities and Personal Strength
      increased during exposure therapy, and these increases were associated to
      decreases of PTSD symptoms. Pretreatment posttraumatic growth, more specifically
      the Appreciation of Life subscale, predicted better treatment outcome after
      controlling for pretreatment PTSD. The results indicate that posttraumatic growth
      may be a valuable new concept in trauma therapy.

PMID- 20690198
TI  - Polycystic kidney disease: Promising new potential therapies for patients with
      autosomal dominant polycystic kidney disease.

PMID- 20690199
TI  - Hypertension: Reducing intake of sugary drinks decreases blood pressure.

PMID- 20690197
TI  - Comparative risk-adjusted mortality outcomes after primary surgery, radiotherapy,
      or androgen-deprivation therapy for localized prostate cancer.
AB  - BACKGROUND: Because no adequate randomized trials have compared active treatment
      modalities for localized prostate cancer, the authors analyzed risk-adjusted,
      cancer-specific mortality outcomes among men who underwent radical prostatectomy,
      men who received external-beam radiation therapy, and men who received primary
      androgen-deprivation therapy. METHODS: The Cancer of the Prostate Strategic
      Urologic Research Endeavor (CaPSURE) registry comprises men from 40 urologic
      practice sites who are followed prospectively under uniform protocols, regardless
      of treatment. In the current study, 7538 men with localized disease were
      analyzed. Prostate cancer risk was assessed using the Kattan preoperative
      nomogram and the Cancer of the Prostate Risk Assessment (CAPRA) score, both well
      validated instruments that are calculated from clinical data at the time of
      diagnosis. A parametric survival model was constructed to compare outcomes across
      treatments adjusting for risk and age. RESULTS: In total, 266 men died of
      prostate cancer during follow-up. Adjusting for age and risk, the hazard ratio
      for cancer-specific mortality relative to prostatectomy was 2.21 (95% confidence
      interval [CI], 1.50-3.24) for radiation therapy and 3.22 (95% CI, 2.16-4.81) for
      androgen deprivation. Absolute differences between prostatectomy and radiation
      therapy were small for men at low risk but increased substantially for men at
      intermediate and high risk. These results were robust to a variety of different
      analytic techniques, including competing risks regression analysis, adjustment by
      CAPRA score rather than Kattan score, and examination of overall survival as the
      endpoint. CONCLUSIONS: Prostatectomy for localized prostate cancer was associated
      with a significant and substantial reduction in mortality relative to radiation
      therapy and androgen-deprivation monotherapy. Although this was not a randomized
      study, given the multiple adjustments and sensitivity analyses, it is unlikely
      that unmeasured confounding would account for the large observed differences in
      survival.

PMID- 20690200
TI  - Transplantation: A low donor kidney weight to recipient weight ratio is
      associated with decreased long-term graft survival.

PMID- 20690202
TI  - Chronic kidney disease: Depression is associated with poor outcomes in early CKD.

PMID- 20690201
TI  - Diabetes: A new urinary marker predicts progression to albuminuria and risk of
      death in patients with type 1 diabetes mellitus.

PMID- 20690203
TI  - Diabetes: Serum uric acid level is associated with early GFR loss in type 1
      diabetes.

PMID- 20690204
TI  - IDF: putting women and diabetes on the global agenda.

PMID- 20690205
TI  - [A rational approach to the treatment of diffuse large-cell lymphomas].

PMID- 20690206
TI  - [If one would again talk about the CHART protocol].

PMID- 20690207
TI  - [Implications of genetic risk factors in breast cancer: culprit genes and
      associated malignancies].
AB  - Our understanding of hereditary forms of breast cancer has made enormous advances
      over the past 15 years, based on epidemiological and molecular genetic studies,
      and the development of a vast number of informative genetic markers. These
      studies have involved women with both familial and sporadic forms of breast
      cancer. Genetic susceptibility to breast cancer can involve several modes of
      inheritance: Mendelian inheritance, mostly involving autosomal dominant mutations
      with high penetrance and a high risk of malignancy (the BRCA1, BRCA2, TP53, PTEN
      and STK11 genes); dominant mutations associated with a lower risk (ATM, BRIP1,
      PALB2, etc), and multigenic patterns involving common susceptibility variants,
      i.e., polymorphisms located within predisposing gene loci (FGFR2, TNRC9, MAP3K1,
      LSP1, etc.) or intergenic regions. Other predisposing factors remain to be
      discovered, as genetic factors associated with a high breast cancer risk (BRCA1,
      BRCA2, TP53, PTEN STK11, etc) are only found in about 20% of genetically screened
      breast cancer families. So far, only the first class of genes have found clinical
      applications, guiding the choice of medical or surgical treatment. More refined
      individual risk profiles will benefit from genome-wide polymorphic DNA variant
      studies anda better understanding of the impact of non genetic factors, such as
      the obstetrical and gynaecological history, and mutagen exposure.

PMID- 20690208
TI  - Annual Report of the Australian Gonococcal Surveillance Programme, 2009.
AB  - The Australian Gonococcal Surveillance Programme (AGSP) monitors antibiotic
      susceptibility testing of Neisseria gonorrhoeae isolated in all states and
      territories. In 2009 the in vitro susceptibility of 3,220 isolates of gonococci
      from public and private sector sources was determined by standardised methods.
      Varying antibiotic susceptibility patterns were again seen across jurisdictions
      and regions. Resistance to the penicillins nationally was 36% and, with the
      exception of the Northern Territory, ranged between 19% in Queensland and 52% in
      Victoria. Quinolone resistance, most at high minimal inhibitory concentration
      (MIC) levels, was 43% nationally (excepting the Northern Territory), and ranging
      from 30% in Queensland to 60% in Victoria. Decreased susceptibility to
      ceftriaxone (MIC 0.06 mg/L or more), was found nationally in 2% of isolates.
      Nationally, all isolates remained sensitive to spectinomycin. Azithromycin
      resistance surveillance was performed in New South Wales, Queensland, Western
      Australia, the Northern Territory and South Australia, and was found to be
      present in low numbers of gonococci with MIC values up to 16 mg/L. In larger
      urban centres the ratio of male to female cases was high, and rectal and
      pharyngeal isolates were common in men. In other centres and in rural Australia
      the male to female ratio of cases was lower, and most isolates were from the
      genital tract.

PMID- 20690209
TI  - [Differential plasma protein profiles in patients with hyperlipidemia &
      atherosclerosis of different patterns of phlegm-stasis syndrome].
AB  - OBJECTIVE: To investigate the differential plasma protein profiles in patients
      with hyperlipidemia & atherosclerosis (H&A) of different patterns of phlegm
      stasis syndrome (PSS) for seeking their biomarker proteins. METHODS: Two
      dimensional gel electrophoresis and gel screening graphical analysis were
      performed on plasma proteins got from 146 patients; corresponding protein spots
      were fetched from the gel for two-stage mass-spectrometric analysis by quadruple
      time-of-flight mass spectrometry; then the differential proteins for PSS were
      discriminated by Fisher discriminate analysis. RESULTS: Excepting two uncertain
      proteins, 7 differential proteins were screened out from the 11 differentially
      expressed plasma protein spots with variability over 100% in the inter-block
      matching. Classic analysis found that haptoglobin precursor and fibrinogen gamma
      chain were possibly the plasma biomarker proteins for H & A; fibrinogen beta
      chain and apolipoprotein A-I precursor were that set apart PSS from non-PSS;
      fibrinogen gamma chain, albumin and apolipoprotein A-I precursor were for phlegm
      syndrome; haptoglobin precursor, adrenomedullin binding protein precursor,
      albumin and complement component C4 were for stasis syndrome; albumin and
      adrenomedullin binding protein precursor were for the phlegm-stasis mutual
      blocking syndrome. Moreover, the above mentioned expressions of possible marker
      proteins had their own special rule of changing in the transforming progress of
      PSS. CONCLUSION: This study reported, for the first time, the existence of
      evident variation of functional protein constitution in different patterns of
      PSS, and definite compatibility being detected in some functional proteins, which
      may be the marker proteins for making diagnosis and prognosis of PSS in H&A.
      Besides, preliminary proof for the transformation of PSS has gained at the
      functional protein level.

PMID- 20690210
TI  - Current concept of anxiety: implications from Darwin to the DSM-V for the
      diagnosis of generalized anxiety disorder.
AB  - This article proposes a revision of the historical evolution of the concepts of
      generalized anxiety disorder (GAD). Currently, Darwin's evolutionary theory is
      the hegemonic paradigm for modern science and influences research on mental
      disorders. Throughout the 20th Century, the editions of the Diagnostic and
      Statistical Manual of Mental Disorders (DSM; American Psychiatric Association)
      have changed the diagnostic criteria for GAD, reflecting the prevailing
      psychiatric understanding of this disorder. The prevalence and symptoms of major
      depression and GAD show the fragility of the categorical conception of these
      conditions. Differences in cultural views towards anxiety disorders also suggest
      that anxiety cannot have a uniform definition. This article provides
      contributions for reflecting future guidelines concerning the diagnostic criteria
      for GAD in DSM-V.

PMID- 20690211
TI  - ["Getting the youngsters off the street corners": accounts of the Social
      Democrats and sports in Copenhagen].

PMID- 20690212
TI  - [Social conflicts and documentary films: three accounts of a funeral in Adalen on
      21 May 1931 as presented in three documentary films].

PMID- 20690213
TI  - [Witch-hunts in the German Social Democratic view of history before 1914: Emil
      Rosenow's Wider die Pfaffenherrschaft].

PMID- 20690214
TI  - "The highest type of Englishman": gender, war, and the Alfred the Great millenary
      commemoration of 1901.

PMID- 20690215
TI  - [Labor market, schooling, and child labor in an agricultural and industrial
      district, the Valles Occidental, 1881-1910].

PMID- 20690216
TI  - [Learning to be women: girls' schools in 19th-century Spain].

PMID- 20690217
TI  - [The charge of ritual homicide: 11 letters written by Girolamo Tartarotti to
      Benedetto Bonelli, 1740-46].

PMID- 20690218
TI  - The impact of clearance and irrigation on the environment in the Lake Erhai
      catchment from the ninth to the nineteenth century.

PMID- 20690219
TI  - [Problems and limitations of the international diffusion of a French method of
      managing urban services: water treatment and distribution].

PMID- 20690220
TI  - [A business history of the Compagnie generale des eaux, 1852-1952: from its
      inception to its renaissance].

PMID- 20690221
TI  - [Specializing in large housing estates: the SAE in France, 1945-74].

PMID- 20690222
TI  - Towards innovation and a partnership future for mental health nursing.

PMID- 20690223
TI  - Transcultural mental health nursing in Malaysia: perspectives and strategies.

PMID- 20690224
TI  - Strategies for advancing psychiatric-mental health nursing science relevant to
      practice. Perspectives from the American Psychiatric Nurses Association research
      council co-chairs.

PMID- 20690225
TI  - Splenic metastasis from cervical cancer: case report and review of the
      literature.
AB  - Cervical cancer isolated splenic recurrence is a rare event.We report a case of
      splenic cervical cancer metastasis treated with salvage surgery 30 months after
      supralevator anterior pelvic exenteration. In this patient the plasmatic level of
      squamous cell carcinoma antigen increased in the absence of any evidence of
      disease at the instrumental examination 24 months after surgery. Surgery had a
      high impact on quality of life.

PMID- 20690226
TI  - The apostle of Italian sport: Angelo Mosso and English athleticism in Italy.

PMID- 20690227
TI  - Missing middle-class dimensions: elementary schools, imperialism and athleticism.

PMID- 20690228
TI  - The living legacy: classical sport and nineteenth-century middle-class
      commentators of the German-speaking nations.

PMID- 20690229
TI  - Unrecognized middle-class revolutionary? Michael Cusack, sport and cultural
      change in nineteenth-century Ireland.

PMID- 20690230
TI  - A tranquil transformation: middle-class racing "revolutionaries" in nineteenth
      century England.

PMID- 20690231
TI  - Mostly middle-class cycling heroes: the fin de siecle commercial obsession with
      speed, distance and records.

PMID- 20690232
TI  - Civilian Health and Medical Program of the Uniformed Services (CHAMPUS); TRICARE
      Retired Reserve for members of the Retired Reserve. Interim final rule with
      comment period.
AB  - This interim final rule establishes requirements and procedures for
      implementation of TRICARE Retired Reserve. This interim final rule addresses
      provisions of the National Defense Authorization Act for Fiscal Year 2010 (NDAA
      10). The purpose of this interim final rule is to establish the TRICARE Retired
      Reserve program that implements section 705 of the NDAA-10. Section 705 allows
      members of the Retired Reserve who are qualified for non-regular retirement, but
      are not yet 60 years of age, to qualify to purchase medical coverage equivalent
      to the TRICARE Standard (and Extra) benefit unless that member is either enrolled
      in, or is eligible to enroll in, a health benefit plan under Chapter 89 of Title
      5, United States Code, as well as certain survivors. The amount of the premium
      that qualified members pay to purchase these benefits will represent the full
      cost as determined on an appropriate actuarial basis for coverage under the
      TRICARE Standard (and Extra) benefit including the cost of the program
      administration. There will be one premium for member-only coverage and a separate
      premium for member and family coverage. The rules and procedures otherwise
      outlined in Part 199 of 32 CFR relating to the operation and administration of
      the TRICARE Standard and Extra programs including the required cost-shares,
      deductibles and catastrophic caps for retired members and their dependents will
      apply to this program. The rule is being published as an interim final rule with
      comment period in order to comply with statutory effective dates.

PMID- 20690233
TI  - TRICARE; rare diseases definition. Final rule.
AB  - This final rule revises the definition of rare diseases to adopt the definition
      of a rare disease as promulgated by the National Institutes of Health, Office of
      Rare Diseases. The rule modification will result in the definition used by the
      TRICARE program for a rare disease to be consistent with the definition used by
      the National Institutes of Health and the Food and Drug Administration. TRICARE
      has generally been applying the broader National Institutes of Health and Food
      and Drug Administration definitions when making coverage decisions for
      treatments; therefore, there will be no practical changes for beneficiaries.

PMID- 20690234
TI  - [The Great War on the front line].

PMID- 20690235
TI  - Yellow fever and geopolitics: environment, epidemics, and the struggles for
      empire in the American tropics, 1650-1900.

PMID- 20690236
TI  - TRICARE: changes included in the National Defense Authorization Act for Fiscal
      Year 2007; improvements to descriptions of cancer screening for women. Final
      rule.
AB  - The Department is publishing this final rule to implement section 703 of the
      National Defense Authorization Act (NDAA) for Fiscal Year 2007 (FY07), Public Law
      109-364. Specifically, that legislation authorizes breast cancer screening and
      cervical cancer screening for female beneficiaries of the Military Health System,
      instead of constraining such testing to mammograms and Papanicolaou smears. The
      rule allows coverage for "breast cancer screening" and "cervical cancer
      screening" for female beneficiaries of the Military Health System, instead of
      constraining such testing to mammograms and Papanicolaou tests. This rule ensures
      new breast and cervical cancer screening procedures can be added to the TRICARE
      benefit as such procedures are proven to be a safe, effective, and nationally
      accepted medical practice. This amends the cancer specific recommendations for
      breast and cervical cancer screenings to be brought in line with the processes
      for updating other cancer screening recommendations. In response to public
      comment on the proposed rule, this final rule includes a clarification that the
      benefit encompasses screening based on Health and Human Services guidelines.

PMID- 20690237
TI  - A matter of fact rather than principle: women, work and property in Papal Rome
      (eighteenth-nineteenth centuries).

PMID- 20690238
TI  - The scourge of "the scurvy": a mariners' occupational disease.

PMID- 20690239
TI  - [Supply in the Third Reich].

PMID- 20690240
TI  - [The creole fever: doctors and faith healers in Cumana during the 18th century].

PMID- 20690241
TI  - [The birth of "self-renewal centers": detention facilities and regional systems
      in the Jiangnan Delta during the mid-Qing era].

PMID- 20690242
TI  - "Jonathan's great knife": Dracula meets Jack the Ripper.

PMID- 20690243
TI  - [2009 report from the Japan Poison Information Center].

PMID- 20690244
TI  - The need for ethics committees in evaluating (women's reproductive health)
      research protocols in African countries.

PMID- 20690245
TI  - Family life and HIV/AIDS education (FLHE) in schools in Enugu State: baseline
      study of reproductive health issues among in-school adolescents in Enugu State.
AB  - We studied the sexual and reproductive health (SRH) knowledge and practices among
      junior secondary school grades 1 and 3 students Enugu State, preparatory to
      incorporating family life and HIV/AIDS education (FLHE) into the school curricula
      in the state. Results show that over 90% of the respondents were regularly
      involved in sexual activities. More than seventeen per cent (17.5%) indicated
      that they would definitely have sex in the next two years while 19.2% may have
      sex in the next two years. The students lacked proper knowledge of protection and
      knowledge scores on SRH issues was low especially among the urban dwellers (p <
      0.001). Some respondents (64.4%) did not know if condoms prevent pregnancy. Some
      indicated that charms and herbs are effective ways of preventing pregnancy.
      Against this background, the opinion leaders and community members welcome the
      FLHE for improving youth knowledge on SRH issues and pledge their support for the
      programme.

PMID- 20690246
TI  - Vulnerability of Nigerian secondary school to human sex trafficking in Nigeria.
AB  - Sex trafficking contributes to the cycle of violence against women, and inflicts
      global social and health consequences, particularly in this era of HIV/AIDS
      pandemic. This paper is based on a cross-sectional survey conducted in two urban
      and two rural schools located in Delta and Edo states of Nigeria. The aim is to
      assess in-school students' knowledge and awareness of, and attitude toward sex
      trafficking as a way to understanding their personal vulnerability to
      trafficking. A semi-structured questionnaire was administered in 2004-2005 to a
      classroom random sample of 689 adolescents in the age range of 16-20 years. The
      results show that in-school adolescents are vulnerable to sex trafficking due to
      poverty (77.2%); unemployment (68.4%); illiteracy (56.1%); and low social status
      (44.5%). Students in co-ed schools showed higher knowledge and awareness of the
      serious health consequences of trafficking.

PMID- 20690247
TI  - Erectile dysfunction in older male stroke patients: correlation between side of
      hemiplegia and erectile function.
AB  - This study was conducted to determine the effects of hemiplegia on erectile
      function in stroke patients. One hundred and five stroke patients grouped into
      left (61.78 +/- 7.79 years) and 55 right hemiplegic (62.11 +/- 9.32 years) and 40
      age-matched controls (64.00 +/- 8.53 years). The International Index of Erectile
      Function questionnaire was used for data collection. One way analysis of variance
      and Spearman correlation tests were used in data analysis. Erectile function was
      significantly decreased in the both right (IIEF-5, 7.55 +/- 4.07) and left
      hemiplegic groups (IIEF-5, 10.40 +/- 5.70) compared with the control group (IIEF
      5, 20.50 +/- 4.2 7) p < 0.05. Side of hemiplegia significantly correlated with
      erectile dysfunction at p < 0.01. Conclusively, stroke mostly affects erectile
      function of right hemiplegia.

PMID- 20690248
TI  - Alpha-tocopherol levels in milk of exclusively breast-feeding mothers in Benin
      City, Nigeria.
AB  - The influence of prolonged breastfeeding on breast-milk alpha tocopherol was
      assessed in 112 lactating mothers practicing exclusive breast-feeding on term
      infants. The cross sectional study was carried out between May 1st and 30th, 2005
      at the University of Benin/University of Benin Teaching Hospital, Benin City
      among lactating mothers. Employing the Quaife's method, mean alpha-tocopherol
      values were determined in spot samples of breast milk. Though not significant
      mean Breast-milk (BM) alpha-tocopherol tended to decline with maternal age (p >
      0.05) parity (p > 0.05) and duration of breastfeeding. Similarly, family socio
      economic status did not significantly influence mean BM alpha-tocopherol levels.
      Exclusive and or prolonged breast feeding do not predispose the infant to low
      vitamin E supplies through the breast milk. Further studies are advocated to
      evaluate the effects of other biosocial variables on the levels of BM anti
      oxidant vitamins including alpha-tocopherol.

PMID- 20690249
TI  - The acute phase response to parturition: a cross-sectional study in Zimbabwe.
AB  - Parturition triggers an acute phase response, but its magnitude, duration and
      predictors are not well described. We determined serum alpha1-antichymotrypsin
      (ACT) and C-reactive protein (CRP) among 216 women attending postpartum services
      in south-eastern Zimbabwe. Serum CRP peaked during the first week and serum ACT
      around 9 days postpartum. Serum ACT, but not serum CRP, was lower among HIV
      infected women. Multiparity was a negative, and preterm delivery and caesarean
      section were positive predictors of both serum ACT and CRP. There is a need for a
      better understanding of the acute phase response to parturition.

PMID- 20690250
TI  - Serologic survey of specific rubella virus IgM in the sera of pregnant women in
      Makurdi, Benue State, Nigeria.
AB  - Although a major section of pregnant women in Nigeria are immune to rubella
      infection, cases of congenital rubella syndrome are still been seen in hospitals.
      Rubella is not a reportable disease in Nigeria and data of its epidemiology are
      extremely rare. In this study, we estimate the burden of acute rubella virus
      infection among pregnant women during their first trimester in Makurdi-Benue
      State-Nigeria. Anti-rubella IgM were detected using a commercially available
      quantitative enzyme immunoassay. Of the 534 (mean age = 28.1 +/- 1.7 years) sera
      sample tested, 21 (3.9%; 95% CI = +/- 1.64%) were positive for Rubella IgM
      antibodies. We also extrapolated by mathematical modeling that 4.2% represents
      the actual/real susceptible population in Nigeria. There was no significant
      correlations between rubella infection and age (p > 0.05). Although the incidence
      of rubella is low we suggest the antenatal screening and vaccination of all
      females of child bearing age to eliminate this potentially devastating virus in
      the county.

PMID- 20690251
TI  - Audit of referral of obstetric emergencies in Angola: a tool for assessing
      quality of care.
AB  - By auditing various aspects of referrals of obstetric emergencies, we wanted to
      study the effectiveness over time of a recently established network of peripheral
      birth units and two central hospitals in Luanda. 157 women referred for obstetric
      emergencies were studied regarding clinical outcome and process indicators like
      waiting time, partogramme quality and Caesarean section rate (CSR). After a
      change in routines at hospital admission and further partogramme education 92
      referred women were compared with the former. Maternal mortality decreased from
      17.8% to nil in the second. Total mean waiting time was reduced from 13.7 hours
      to 1.2 hours. Partogramme quality was significantly improved. CSR increased from
      13 to 30%. Prolonged labour was the most common diagnosis.This study demonstrates
      the importance of clinic-based audit to enhance quality of care regarding
      referrals of patients with obstetric emergencies.

PMID- 20690252
TI  - Prevention of postpartum hemorrhage: options for home births in rural Ethiopia.
AB  - This paper sought to determine the safety and feasibility of home-based
      prophylaxis of postpartum hemorrhage (PPH) with misoprostol, including assessment
      of the need for referrals and additional interventions. In rural Tigray,
      Ethiopia, traditional birth attendants (TBAs) in intervention areas were trained
      to administer 600mcg of oral misoprostol. In non-intervention areas women were
      referred to the nearest health facility. Of the 966 vaginal deliveries attended
      by TBAs, only 8.9% of those who took misoprostol prophylactically (n = 485)
      needed additional intervention due to excessive bleeding compared to 18.9% of
      those who did not take misoprostol (n = 481).The experience of symptoms among
      those who used misoprostol can be considered of minor relevance and self
      contained. This study found that prophylactic use of misoprostol in home births
      is a safe and feasible intervention. Community health care workers trained in its
      use can correctly and effectively administer misoprostol and be a champion in
      reducing PPH morbidity and mortality.

PMID- 20690253
TI  - The prevalence of dual human immunodeficiency virus/hepatitis C virus (HIV/HCV)
      infection in asymptomatic pregnant women in Benin City, Nigeria.
AB  - Concerted efforts have been made to combat HIV infection in Nigerian. By
      contrast, much less attention has been paid to hepatitis C viral (HCV) infection.
      These viruses have similar immuno-epidemiology. The objective of this study was
      to determine the prevalence of HCV/HIV dual infection among 269 antenatal
      attendees at the University of Benin Teaching Hospital in southern Nigeria. The
      study was prospective and cross-sectional and consisted of the analysis of the
      sera of the participants for anti-HCV and HIV antibodies using ELISA. The result
      showed that 1.86% samples were HCV antibodies positive while 8.30% were
      seropositive for HIV-1 antibodies. There were no cases of dual infections. The
      HIV positive women and their babies had antiretroviral therapy. We conclude that
      dual HCV/HIV infection in pregnancy in Nigeria may be uncommon but suggest
      multicenter studies to determine the national prevalence while initiating
      strategies for their prevention.

PMID- 20690254
TI  - Relative contributions of socio-cultural variables to the prediction of maternal
      mortality in Edo South Senatorial District, Nigeria.
AB  - The study examined the extent of contributions of socio-cultural factors to
      maternal mortality (through survey method). Two thousand one hundred and fifty
      seven (2,157) females of reproductive age were selected using multi-stage
      sampling technique. The instrument was a self developed structured and validated
      questionnaire with a reliability of 0.82. Focus Group Discussion (FGD) and In
      depth interview guide were used to complement the instrument. Inferential
      statistics of multiple regression was employed to test the hypothesis at 0.05
      level of significance. The result showed that the most relevant variables across
      the two locations (rural and urban) was early marriage/early child bearing (R2 =
      0.200; F = 401.40; P = 0.001) followed by educational attainment. Others in
      descending order were: women decision making power; traditional obstetric care
      services; female genital mutilation; economic status and access to health care
      service. This indicates the importance of formulating policies that would focus
      on attaining high level of literacy among girls.

PMID- 20690255
TI  - Community-based availability of misoprostol: is it safe?
AB  - This paper evaluates the safety and acceptability of long-term community-based
      use of misoprostol for management of postpartum hemorrhage (PPH) in home-births,
      by comparing deliveries with and without misoprostol use in communities of
      Kigoma, Tanzania. We administered a standardized survey instrument to women who
      delivered between August 2004 and May 2007. 940 women completed questionnaires,
      corresponding to 950 deliveries. Findings showed that the majority of TBAs
      administered misoprostol at the correct time (76%). Receipt of three or five
      tablets was most commonly reported (47% and 43% respectively). Misoprostol users
      were significantly more likely to experience shivering, high temperature, nausea,
      and vomiting after delivery; adjustment for gynecological history and delivery
      characteristics revealed no significant differences in experience of symptoms.
      Misoprostol was highly acceptable to all women surveyed. Misoprostol at the
      community level is a safe intervention.

PMID- 20690256
TI  - Expanding comprehensive postabortion care to primary health facilities in Geita
      District, Tanzania.
AB  - A postabortion care program was implemented in 11 primary and secondary health
      facilities in rural Tanzania in order to decentralize comprehensive postabortion
      care to community level by upgrading midlevel providers to perform manual vacuum
      aspiration (MVA). Information about evacuation procedure and family planning (FP)
      service provided was obtained from the health facilities. In all, 2025
      evacuations had been performed with MVA and D&C accounting for 65.6% and 34.4%,
      respectively. Among the women admitted with abortion complications, 59.8% left
      with a FP method. The proportion of women offered FP service differed by
      evacuation procedure, hence the proportion was higher among women evacuated by
      MVA. Upgrading midlevel providers to perform MVA is an efficient means to address
      the problem of unsafe abortion in rural areas. However, the sustainability of MVA
      service provision remains a challenge. Moreover, FP services should be offered to
      all postabortion clients regardless of evacuation procedure.

PMID- 20690257
TI  - Correlates of abortion related maternal mortality at the Lagos State University
      Teaching Hospital, Ikeja.
AB  - This study was carried out to highlight the probable correlates of mortality
      among patients managed for abortion related complications at the Lagos State
      University Teaching Hospital, Ikeja. All patients managed for abortion related
      complications between 1st January 2000 and 31st December 2003 were studied.
      Certain relevant socio demographic and clinical factors were compared among the
      survivors and fatalities. There were a total of 338 patients with abortion
      related complications. 299 survived while 39 died. Being single, nulliparous, of
      low educational status, presenting late and having major complications were
      significantly associated with mortality in this series. Encouragement of safe sex
      practices, increasing adolescents' access to contraception, additional training
      of physicians and other appropriate heath workers in abortion care as well as the
      liberalisation of the restrictive abortion laws in Nigeria will go a long way in
      reducing abortion related mortality.

PMID- 20690258
TI  - The struggle to reduce high maternal mortality in Nigeria.
AB  - According to UNICEF estimates for Nigeria, maternal mortality ratio is 1100 per
      100,000 live births, antenatal care coverage 47 percent, institutional delivery
      rate 33 percent, and each woman bears six children on the average. Reducing the
      high maternal mortality ratio, which is the prime concern, has hitherto
      concentrated on transforming the health system through bringing resources and
      expertise to bear on the high maternal mortality per se including some of its
      surrounding elements. It has failed. High maternal mortality must be tackled at a
      much more fundamental level. In the complexities and uniqueness of Nigeria's
      current situation, it is suggested that the fundamental remedy is to stamp out
      the chaos in the country by getting the politics and governance structures right.
      Accurate population census is paramount. Compulsory registration of births and
      deaths, fixing the broken-down educational system and bringing back the public
      service ethos the country once had, are core issues.

PMID- 20690260
TI  - Changes in knowledge and attitudes among junior secondary students exposed to the
      family life and HIV education curriculum in Lagos State, Nigeria.
AB  - To address the needs of young people in Lagos State, Nigeria, for information
      about family life and HIV, the Lagos State Ministry of Education, in
      collaboration with Action Health Incorporated, began to offer the Family Life and
      HIV Education Curriculum in government junior secondary schools in 2003.
      Knowledge and attitudes were measured in a sample of 1,366 students in Lagos
      State, Nigeria, in November 2004, at the beginning of the school year, and again
      in July 2005 after receiving a year of the Family Life and HIV Education
      Curriculum. Students exposed to the curriculum significantly increased knowledge
      of sexuality and HIV, support for abstinence, and gender role equality.

PMID- 20690259
TI  - HIV/AIDS-related stigma and discrimination in Nigeria: review of research studies
      and future directions for prevention strategies.
AB  - Human Immunodeficiency Virus (HIV) infection and AIDS remain a major public
      health crisis in Nigeria which harbors more people living with HIV than any other
      country in the world, except South Africa and India. A significant challenge to
      the success of achieving universal access to HIV prevention, treatment, care and
      support by 2010 is HIV-AIDS stigma and discrimination. Eight studies looking at
      some degree of measurement of stigma and discrimination in Nigeria were reviewed
      in an attempt to investigate the cultural context of stigma, health seeking
      behavior and the role both perceived and community stigma play in HIV prevention.
      Results suggest that reducing stigma does increase the individual as well as
      community acceptance of people living with HIV-AIDS (PLWHAs), but long term
      studies are needed. Some suggestions are recommended for future research on
      culture specific stigma studies in Nigeria.

PMID- 20690261
TI  - High prevalence of anti-D antibodies among women of childbearing age at Centre
      Pasteur of Cameroon.
AB  - We conducted a cross sectional retrospective study to determine anti-D and D
      negative phenotype rates among Cameroonian women of reproductive age (15-44
      years), in order to evaluate the importance of D alloimmunization. Analysis of
      the haematology laboratory records from January 2006 to December 2007 harvested
      225 results for red blood cell alloantibody screening and 2460 D phenotypes. Anti
      D rate was found to be high at 4% and not linked to women's parity. Three hundred
      and fifty two (14.3%) women were found to be D-negative. Anti-D rates
      significantly decreased with age from 18.8% among teenagers (15-19) to 7.8% among
      older women (35-44) (p = 0.001). The number of women submitted to both irregular
      antibody screening and type D phenotype determination was not strong enough (50)
      to analyse the link between anti-D rate and antigen D distribution in our study.

PMID- 20690262
TI  - Modeling contextual determinants of HIV/AIDS prevalence in South Africa to inform
      policy.
AB  - There is a voluminous literature on HIV/AIDS and South Africa. However, no study
      focuses on the modeling of contextual factors concerning HIV/AIDS prevalence in
      South Africa. In this paper, two models of contextual behavioral risk factors of
      HIV/AIDS prevalence were developed so that policy makers can be alerted to the
      key variables in order to help curb the spread of the disease. It was found that
      fearlessness/low-perception, poverty and hopelessness risks are determinants of
      an active risk factor. While the latter and passive risk factor (i.e. gender
      dependency) are the determinants of HIV/AIDS prevalence. As a result, it was
      argued to go beyond the KABP determinant studies to focus on contextual
      behavioral risk factors and pointed out that further research is needed on the
      limit of contextuality of risk factors. In conclusion, policies were suggested to
      help curb the spread of HIV/AIDS.

PMID- 20690263
TI  - Correlates of fertility intentions among HIV/AIDS patients in northern Nigeria.
AB  - Little research has been conducted regarding the reproductive intentions of
      people living with HIV/AIDS (PLWHA) in northern Nigeria. We studied reproductive
      desires and their predictors among 340 PLWHA receiving care at Aminu Kano
      Teaching Hospital. Of all respondents, 60 (70.6%) of males and 177 (69.4%) of
      females were sexually active. Only 65 (19.4%) of them used condoms. One hundred
      and sixty seven females (65.5%) and 52 (61.2%) males expressed a desire to have
      more children. Out of these, 16 (7.3%), 106 (48.4%) and 88 (40.2%) wanted to have
      one, two and three or more children respectively. Significant predictors of
      higher fertility desires were; religion (OR=1.8), duration of diagnosis
      (OR=0.42), low parity (OR=6.03) and awareness of partner's scrostatus (OR=2.3). A
      large proportion of the HIV-positive individuals in the study were sexually
      active, desired to have children, and wanted to use family planning, indicating
      unmet need for reproductive health counseling in general and family planning in
      particular.

PMID- 20690264
TI  - The impact of infertility on infertile men and women in Ibadan, Oyo State,
      Nigeria: a qualitative study.
AB  - This study explored the impact of infertility on infertile men and women in
      Ibadan, Nigeria. The qualitative study design included the application of focus
      group discussions with community members (7 FGDs, n=42), in-depth interviews with
      infertile men (n=7), infertile women (n=8) and professionals (n=13). The findings
      revealed that infertile men and women and community members commonly perceived
      that contraceptives and abortion cause infertility, as well as supernatural and
      behavioural factors. Measures to prevent infertility were not well known by the
      participants. Infertility treatment is sought from a mixture of biomedical, faith
      based and traditional service providers. Infertile women prioritize the
      psychological impact of infertility while infertile men prioritize the economic
      impact, and reported spending between 55-100% of their income to address
      infertility. Infertility has a serious social, psychological and economic impact
      on women and men's lives. Efforts to reduce the impact should prioritize
      education on the causes, prevention and treatment of infertility, offer
      psychological support and ensure an efficient referral system for managing
      infertility.

PMID- 20690265
TI  - Volunteerism among out-of-school adolescent reproductive health peer educators:
      is it a sustainable strategy in resource constrained countries?
AB  - Out-of-school peer educators [PE] are resourceful in transmitting reproductive
      health information but their retention remains a contentious issue. This study
      aimed to assess motivation and sustainability of out-of-school PEs in
      disseminating reproductive health information among adolescents. A structured
      questionnaire was used to interview 406 PEs in Mbeya region, Tanzania. Focus
      Group Discussions [FGDs] were also conducted with the PEs and other relevant
      stakeholders. Most PEs had hopes for future employment and allowances through
      continuous training. The fact that majority of PEs had primary level education
      [89%] and were either peasants or self employed [92%] posed a serious question as
      to whether voluntary work is for the less educated, peasants and self-employed.
      Sustenance of PEs needs to be a continuous activity aimed at increasing the
      number of trained adolescents from their own social and economic groups.
      Otherwise, provision of transport and compensation for time spent should be
      considered.

PMID- 20690266
TI  - Utilization of antenatal care and delivery services in Sagamu, south western
      Nigeria.
AB  - A survey of 392 women who had carried at least one pregnancy to term in Sagamu,
      South-Western Nigeria was conducted to determine the pattern of use of maternity
      services and assess factors that may influence the observed pattern. Majority of
      the women received antenatal care (84.6%) during their last pregnancy. Four-fifth
      of those who received ANC first attended the clinic during the second trimester
      (79.6%). The places of delivery were government facilities (54.8%), private
      hospital (24.5%), traditional birth attendants (13.5%) and spiritual healing
      homes (5.6%). Higher educational status and higher level of income positively
      affected the pattern of use of these services (p<0.05). Perceived quality of
      service was the most important factor which influenced the choice of facility for
      obstetric care. A considerable proportion of those who used traditional birth
      attendants (36.1%) used it to please their husbands. Our findings suggest that
      improving the socioeconomic status of men and women in the community is a key
      factor to improving utilization of maternity care services.

PMID- 20690267
TI  - Deficiency of alpha-tocopherol in seminal fluid as a probable factor in low
      fertility in Cote d'Ivoire.
AB  - To evaluate the level of alpha-Tocopherol in seminal fluid of patients with low
      fertility, forty subjects with low fertility (17 with asthenospermia and 32 with
      oligoasthenospermia) and 21 subjects with normal sperm parameters were recruited
      into this study for assessing their alpha-Tocopherol seminal fluid level. The
      mean level of alpha-Tocopherol in subjects with normal sperm profile was 0.62
      micromol/l compared to those with pathological profile such as asthenospermia
      (0.29 micromol/l) and oligoasthenospermia (0.28 micromol/l). The determination of
      alpha-Tocopherol in human seminal fluid provides useful information concerning
      the exploration of low fertility in Cote d'Ivoire.

PMID- 20690268
TI  - Conjoined twins in Cameroon: issues inherent in diagnosis and management in the
      African context.
AB  - Conjoined twins represent one of the rarest forms of congenital abnormalities. We
      present a case of conjoined twins delivered at born in the Yaounde Gynaeco
      Obstetric and Pediatric Hospital in Cameroon. They were joined at the chest and
      abdomen, and had one functional heart. The outcome was fatal on the seventh day
      of life, despite appropriate reanimation measures. This case highlights the
      difficulties inherent in the diagnosis and management of conjoined twins in low
      resource settings.

PMID- 20690269
TI  - Schistosomiasis and vesicovaginal fistula.
AB  - Schistosoma haematobium is presented as a cause of vesicovaginal fistula in a
      nulliparous adolescent. The possible role of S. haematobium in failure of fistula
      repair and the importance of screening and treatment in endemic areas prior to
      repair are discussed.

PMID- 20690270
TI  - Ethics, bio-ethics and environment in healing designs.

PMID- 20690271
TI  - Hypertension in pregnancy among HIV-infected women in sub-Saharan Africa:
      prevalence and infant outcomes.
AB  - This analysis was performed to determine the prevalence of hypertension and
      association of MAP (mean arterial pressure) with birth outcomes among HIV
      infected pregnant women not taking antiretrovirals. HIV-infected pregnant women,
      enrolled into the HPTN024 trial in Tanzania, Malawi and Zambia were followed up
      at 26-30, 36 weeks, and delivery. The prevalence of hypertension was <1% at both
      20-24 weeks and 26-30 weeks and 1.7% by 36 weeks. A 5 mm Hg elevation in MAP
      increased the risk of stillbirth at 20-24 weeks by 29% (p = 0.001), 32% (p =
      0.001) at 26-30 weeks and of low birth weight (LBW) at 36 weeks by 26% (p =
      0.001). MAP was not associated with stillbirth at 36 weeks, LBW prior to 36
      weeks, preterm birth, neonatal mortality or the risk of maternal to child
      transmission (MTCT) of HIV.

PMID- 20690272
TI  - Sexual and reproductive health knowledge, behaviour and education needs of in
      school adolescents in northern Nigeria.
AB  - Adolescence is marked by progression from the appearance of secondary sexual
      characteristics to sexual and reproductive maturity. Curiosity about bodily
      changes is heightened. However, adolescents' perceived sexuality education needs
      have been poorly documented. A survey of 989 adolescents from 24 North-Eastern
      Nigerian secondary schools yielded information on socio-demographic
      characteristics, reproductive health knowledge, sexual activities and sexuality
      education needs. Of the interviewed respondents, 72% of females had experienced
      menstruation. Overall, 9% were sexually active, 3.1% knew when ovulation occurs,
      47% knew pregnancy could result from first coitus and 56% knew of contraception.
      84% opined that adolescents should be given sexuality education but only 48.3%
      had received any. Sexuality education should be provided for in-school
      adolescents through their preferred and reliable sources of information.

PMID- 20690273
TI  - Knowledge, attitude and practices study on reproductive health among secondary
      school students in Bolgatanga, upper east region, Ghana.
AB  - This study was conducted within the secondary school student population of the
      Bolgatanga community, in Northern Ghana, to learn about knowledge, attitude and
      practices of reproductive health of this adolescent student population. Both
      quantitative and qualitative data were collected on adolescence perception, STIs
      and HIV/AIDS, family planning, male-female relationship, and vulnerability to
      sexual violence. The data collected show a concerning low familiarity of the
      student population with family planning methods and HIV/AIDS transmission, which,
      combined with minimal contraceptive use, pose them at high risk for unwanted
      pregnancies and sexual infections transmission. We argue that poor
      infrastructures and low accessibility of these rural areas in Northern Ghana may
      have led to uneven distribution of reproductive health educational programs in
      the country, urging more programs and interventions aimed particularly at these
      high risk groups.

PMID- 20690274
TI  - Maternal mortality in a transitional hospital in Enugu, south east Nigeria.
AB  - Nigeria has one of the highest maternal mortality ratios in the world. The study
      was to determine the trend of maternal mortality ratio in the hospital as it
      transits from a General through a Specialist to a Teaching hospital. It was a
      retrospective review of maternal deaths at Enugu State University Teaching
      Hospital Parklane, over its 5 year transition period (January 2004 to December
      2008). There were 7146 live births and 60 maternal deaths giving an overall
      maternal mortality ratio (MMR) of 840/100,000 livebirths. The MMR rose from 411
      to 1137/100,000 live births as a specialist hospital, with a decline to
      625/100,000 as a Teaching hospital. Pre-eclampsia/eclampsia was the leading cause
      (29.63%) of maternal death. MMR was highest as a Specialist hospital due to
      limited manpower and inadequate facilities to properly manage the rising number
      of referred obstetric emergencies. Adequate preparations should be made before
      upgrading a hospital, to enable it cope with the challenges of managing referred
      obstetric emergencies

PMID- 20690275
TI  - Barriers to sustainable MVA supply in Ghana: challenges for the low-volume, low
      income providers.
AB  - Multiple studies have demonstrated that manual vacuum aspiration (MVA) is ideal
      for surgical uterine evacuation in low-resource settings such as Ghana, but
      developing a sustainable supply to MVA has been challenging. In 2007 a
      situational analysis was conducted in Ghana to identify barriers to sustainable
      MVA supply. Information about MVA availability was gathered in seven regions of
      Ghana and obtained through background literature, unpublished data and reports,
      and 70 informational interviews with stakeholders involved with MVA policy,
      manufactufing, procurement, distribution, supply, training, and provision. The
      findings revealed that despite consensus about the dire need for MVA in Ghana,
      developing sustainable access to MVA instruments has proven difficult. In the
      public and the private health sectors, procuring MVA equipment has been
      particularly challenging for low-income, low-volume service providers. Research
      findings yielded ten recommendations for improving sustainable access to MVA,
      including the implementation of a revolving purchase mechanismn for health
      provider associations, such as the Ghana Registered Midwives Association.

PMID- 20690276
TI  - Coping strategies of women seeking infertility treatment in southern Ghana.
AB  - Infertility is a health problem faced by an estimated 15% of women of
      childbearing age in Ghana. This study explores the coping strategies adopted by
      615 women seeking infertility treatment in southern Ghana. Both closed and open
      ended questions were used through a survey conducted using face-to-face
      interviews in three languages at three health sites--a hospital, a health centre
      and a private clinic. The findings suggest that the majority of the women
      preferred to keep issues of their fertility problems to themselves. The reason
      could be due to the associated stigma of infertility. Further, the majority of
      the women coped through drawing on their Christian faith. Others also coped
      through the support they received from their husbands, their occupation by way of
      achieving economic independence, and some avoided situations that reminded them
      of their infertility problem. The findings should have implications for health
      personnel as some strategies infertile women use may do more harm than good.

PMID- 20690277
TI  - Safety studies of a recently developed microbicidal contraceptive gel (UniPron)
      in female baboons (Papio anubis).
AB  - To identify any toxicity on the vaginal epithelium, liver and kidney following
      UIniPron administration, ten healthy female olive baboons (Papio anubis) of
      reproductive age and of proven fertility were used. Five baboons were each
      treated with 15 g of UniPron intravaginally twice a week for 20-weeks and venous
      blood collected before and after each treatment. Venous blood was collected from
      five control animals as in the experimental females, but these control animals
      were not given any treatment. The endpoints that were evaluated included clinical
      chemistry profiles on kidney and liver functions and vaginal histopathology.
      Female baboons treated with 15 g of UniPron intravaginally showed no detectable
      adverse effects on clinical chemistry profiles investigated and vaginal
      histopathology. Repeated intravaginal exposure of female baboons to UniPron did
      not induce detectable vaginal irritation and there were no detectable
      histological changes. We conclude that administration of UniPron into baboon
      vagina did not cause any detectable toxicity.

PMID- 20690278
TI  - Sterilization by minilaparotomy in south-eastern Nigeria.
AB  - The study aimed to assess the trend in acceptance and characteristics of
      acceptors of female sterilization between January 1999 and December 2006 at the
      University of Nigeria Teaching IHospital, linugu, South-Eastern Nigeria. There
      were a total of 20,485 new clients, with 212 (1.0%) accepting sterilization
      between January 1999 and December 2006. There was an initial rise in acceptance
      from 0.4% in 1999 to 3.0% in 2004, then a decline. 108 (50.9%) were between 35-39
      years. 169 (79.7%) had more than five living children. 69 (32.5%) and 76 (35.9%)
      had secondary and higher education respectively. Health workers were the main
      source of information. Completed family size was the reason for choosing
      sterilization in 185 clients (87.3%). 120 (56.6%) were in occupational social
      class 3.106 (50.0%) did not practice any form of family planning prior to the
      procedure. 184 (86.8%) had interval sterilization and the rest (13.2%)
      postpartum. Acceptance of tubal sterilization is still low in our community.

PMID- 20690279
TI  - Poor parenting: teenagers' views on adolescent pregnancies in eastern Uganda.
AB  - In Uganda teenage pregnancy is considered a problem for moral and social, as well
      as health, reasons. This qualitative stud,y in Busia District focused on the
      views of teenagers themselves as expressed in 9 focus group discussions with
      girls and boys. Their perspectives were contrasted with those of community
      leaders and mothers of adolescents. The young people blamed teenage pregnancy on
      failures of the parental generation. They asserted that parents and guardians
      were both too lenient and too harsh, that they failed to provide for their
      daughters' needs, and that they pressured them into early marriages instead of
      giving priority to education. Although poverty and family breakdown were
      recognized as underlying structural causes of parental failure, the teenagers
      experienced these factors in their everyday lives as problems with their parents
      and guardians. The teenagers expressed the 'enlightened' view that adolescent
      pregnancy was undesireable, even though many girls have few alternatives to
      marriage and childbearing.

PMID- 20690280
TI  - Female children with ambiguous genitalia in awareness-poor subregion.
AB  - Congenital aberrations of female children's external genitalia are common
      worldwide with varied mode of presentation especially in regions with poor
      awareness. This prospective experience between July 2004 and June 2008 at two
      Nigerian healthcare facilities is on the mode of presentation and challenges of
      management of female children with ambiguous genitalia. Congenital adrenal
      hyperplasia (CAH) 19 (47.5%), female pseudohermaphroditism 20 (50%) and vaginal
      atresia 1 (2.5%) manifested as aberrations of external genitalia of 40 female
      children who presented between the ages of 3 months and 16 years (average 9
      years). Cultural influence, lack of awareness, inadequate examination of external
      genitalia at birth and lack of diagnostic facilities resulted in late
      presentation and diagnosis with all the cases of CAH and pseudohermaphroditism
      raised as males. Five cases who developed female secondary sexual characteristics
      at puberty attempted suicide before presentation. Gender reassignment and
      feminizing genitoplasty were major challenges, but outcomes were encouraging.

PMID- 20690281
TI  - Estimating the impact of birth control on fertility rate in sub-Saharan Africa.
AB  - Using a cross-country data drawn from 40 countries and a multiple regression
      analysis, this paper examines the impact of birth control devices on the rate of
      fertility in sub-Saharan Africa. Our a-priori expectations are that the more
      women used birth control devices, the less will be the fertility rate in sub
      Saharan Africa. The result obtained from the study indicates that except for
      withdrawal method that fall contrary to our expectation other variables (methods)
      like the use of pills, injection, intra uterine device (IUD), condom/diaphragm
      and cervical cap, female sterilization and periodic abstinence/rhythm fulfilled
      our a-priori expectations. These results notwithstanding, the paper suggests
      measures, such as the need for massive enlightenment campaign on the benefit of
      these birth control devices, the frequent checking of the potency of the devices
      and good governance in the delivery of the devices

PMID- 20690282
TI  - Uncommon cause of acute pelvic pain: isolated torsion of hydrosalpinx.
AB  - Isolated torsion of hydrosalpinx is a rare cause of acute pelvic pain. Pre
      operative diagnosis is very difficult because of non specific clinical
      presentation. Definitive diagnosis is always made at surgical exploration
      performed for suspected adnexal torsion and salpingectomy is performed in the
      majority of cases. A 34-year-old woman was admitted for acute pelvic pain with
      nausea and vomiting. Vaginal examination revealed a right adnexal tender mass and
      ultrasound revealed a well circumscribed right adnexal cystic mass. Surgical
      exploration has revealed torsion of a right hydrosalpinx and right salpingectomy
      was performed. Differential diagnosis between adnexal and tubal torsion is very
      difficult, however both should be managed by rapid surgical exploration which an
      allow precocious diagnosis and conservative treatment.

PMID- 20690283
TI  - HPV vaccine and prevention of cervical cancer in Africa.

PMID- 20690284
TI  - The social context of induced abortions among young couples in Cote d'Ivoire.
AB  - The background of the study is the very high prevalence of mortality and
      morbidity in Sub-Saharan countries due to abortions induced by unsafe methods.
      This paper draws on fieldwork conducted in 1998 and 1999 in the city of Bouake in
      Cote d'Ivoire. The study is based upon qualitative semi-structured interviews
      with men and women. This paper presents some case stories based on interviews
      with young women having had an abortion, or with men having had a young partner
      who has had an abortion, both married and unmarried. It discusses how illegally
      induced abortion may be understood in relation to ongoing social processes
      characterised by economic hardship and tensions between the sexes and
      generations. One important finding is that the young often choose abortion
      because they cannot count on economic and practical assistance from parents in
      feeding and raising the child. Parents are also often pushing their children to
      have an abortion.

PMID- 20690285
TI  - Knowledge about HIV/AIDS and sexual practices among automobile repair workers in
      Ibadan, Southwest Nigeria.
AB  - HIV/AIDS is a rapidly growing epidemic in sub-Saharan Africa. Very few studies
      have focussed on outdoor workers. A cross sectional survey was conducted among
      automobile repair workers in Ibadan, Southwest Nigeria. A structured
      questionnaire was administered by interviewers to collect information on
      knowledge of transmission and prevention of HIV/AIDS and sexual practices among
      automobile repair workers. Twenty five questions were designed to determine
      knowledge about HIV/AIDS, each with a minimum score of 0 and a maximum of 1.
      Eight hundred workers participated in the study. They were all male aged between
      12 and 80 years, mean 29.8 years. About half of the population were single.
      Majority (96%) had heard of HIV/AIDS. Over 95% of respondents knew about
      transmission by sexual intercourse and blood transfusion. A mean knowledge score
      of 17.6 out of 25 was recorded. Several misconceptions such as transmission of
      HIV/AIDS by mosquitoes and through sharing of clothes were prevalent. Ninety
      three percent had ever had sexual intercourse and 87% of singles were sexually
      active. Two hundred and thirty-nine, (30%) had casual sex partners. Of these,
      only 59% used condoms during the last sexual intercourse with casual partners. In
      spite of a high knowledge score among this male dominated low income workers,
      their sexual practices are such that will encourage transmission of HIV.

PMID- 20690286
TI  - Social, economic and demographic determinants of sexual risk behaviors among men
      in rural Malawi: A district-level study.
AB  - Data from a survey of 715 men aged 20-44 from Mangochi district of Malawi were
      used to assess the sociodemographic and economic determinants of (1) having ever
      paid for sex, (2) total number of sex partners in the past year, and (3) having
      ever used condoms. Different individual characteristics were associated with each
      of these sexual behaviors. Polygamy and being a fisherman who has left home for
      over a month in the past year for work reasons were both positively associated
      with having ever paid for sex, whereas those with more household wealth were less
      likely to have paid for sex. The influence of education, age, age at sexual
      initiation, Muslim religion, polygamy, occupation, and having ever paid for sex
      on total number of sexual partners in the past year are all evident. Finally,
      secondary education, work-related migration, and having ever paid for sex were
      significantly associated with having used condoms.

PMID- 20690287
TI  - Evaluation of a school-based reproductive health education program in rural South
      Western, Nigeria.
AB  - This quasi-experimental study compared the relative efficacy of teacher
      instructions alone, peer education alone, and a combination of these two on
      reproductive health knowledge, attitude, perceived self-efficacy and sexual
      practices among secondary schools students in the Ibarapa district of
      Southwestern Nigeria. A baseline questionnaire was administered to a systematic
      sample of students in four schools that were randomized into four treatment arms:
      teacher instructions alone (E1), peer education alone (E2), combination of
      teacher instruction and peer education (E3), and control. The results were used
      to design the contents of the interventions, which were implemented for one
      academic session. A follow-up survey using the same sampling procedures as
      baseline was conducted to measure the outcome of the intervention. The control
      group had superior reproductive health knowledge at baseline. By follow-up survey
      however, all three intervention schools showed significant knowledge gains, while
      the control school students' mean score increased slightly. Increase in knowledge
      was greatest among E3 (+5.0 points), followed by E2 (+3.4), E1 (+1.4) and C
      (0.3). The intervention schools showed a significant positive shift in attitude
      towards use of contraceptives with mean increase of 0.6, 0.5, and 0.9 points in
      E1, E2 and E3 respectively. Scores that measured the students' perceived self
      efficacy for safe sex increased significantly among E1 (from 10.8 to 11.8) and E3
      (from 10.4 to 12.6). Reported condom use was significantly higher among E2 (from
      16.7 % to 62.8%) (p < 0.05) and E3 (from 22.8% to 53%) (p < 0.05) compared to El
      (28.6% to 47.40%) (p > 0.05) and control (from 25% to 45.8%) (p > 0.05). Overall,
      the students from E3 showed more improvement in knowledge, attitude and self
      efficacy, than their counterparts from E2 and E3 and control. Multiple
      intervention strategies have greater potential of improving reproductive health
      of students.

PMID- 20690288
TI  - Introducing the standard days method: expanding family planning options in
      Rwanda.
AB  - The Standard Days Method is a simple fertility awareness-based method of family
      planning that helps women identify the days each cycle when they are most likely
      to conceive. Couples who wish to prevent pregnancy avoid unprotected intercourse
      on these days. The method was introduced in 13 sites in Rwanda, a nation with a
      high level of unmet need for family planning. This was the first time the method
      was introduced into regular service delivery, without the rigorous follow-up of a
      study setting. Users of the Standard Days Method were identified from clinic
      records and participated in interviews and focus groups. Community workers were
      also interviewed. Results confirm that the Standard Days Method is easy for
      providers to teach and for clients to learn and correctly use. The method
      attracts couples who are new to family planning, and is a valuable addition to
      the method mix offered in Rwanda.

PMID- 20690289
TI  - Perception and practice of malaria prophylaxis in pregnancy among health care
      providers in Ibadan.
AB  - The study assessed knowledge and practice of health care providers on current
      concepts on malaria prophylaxis in pregnancy. 497 randomly selected respondents
      at the three levels of care in two local governments in Ibadan, South western
      Nigeria were interviewed using a self-administered questionnaire. Respondents
      were selected from 45 health facilities: 48 (9.7%) community health extension
      workers (CHEWS), 139 (28.9%) auxiliary nurses, 220 (44.3%) formally trained
      nurses and 90 (18.10%) medical doctors. Only 57 (11.5%) respondents were
      knowledgeable about current WHO strategies for malaria prevention in pregnancy.
      Three hundred and eighty six respondents (77.7%) were aware of intermittent
      preventive treatment (IPT). Awareness about IPT was highest among CHEWS (95.8%).
      Pyrimethamine was prescribed mainly by healthcare providers in the secondary
      (60.6%) and primary (60.3%) levels of care (chi2 = 11.54, p < 0.01). Chloroquine
      was prescribed by 42.5% of respondents. Sulfadoxine-pyrimethamine was
      significantly more commonly prescribed by primary health care providers than in
      other levels of care (chi2 = 15.07, p < 0.01). Prescription for insecticide
      treated nets was high. Respondents' practice of anti-malarial chemoprophylaxis
      was influenced by the cadre of the health care provider and level of practice.
      There are several knowledge gaps on current malaria prevention strategies in
      pregnancy among healthcare providers. Multiple strategies are required to improve
      health care workers' knowledge and practice of malaria prevention during
      pregnancy.

PMID- 20690290
TI  - Sustainability and factors affecting the success of community-based reproductive
      health programs in rural northwest Ethiopia.
AB  - arious Community-Based Reproductive Health interventions were initiated in many
      developing countries but their effectiveness has not been evaluated as much as
      needed. A comparative cross sectional study was carried out in February 2002
      among women who participated in community based reproductive health interventions
      in South Gondar zone, Ethiopia. The study was conducted in eight kebeles taking
      successful and weak program areas for comparison. Both quantitative and
      qualitative methods were used for data collection. The qualitative method
      included key informants interview, and Focus Group Discussions with Community
      based reproductive health agents (CBRHAs). A multistage sampling technique was
      employed to select 792 study subjects for the quantitative part of the study.
      Awareness of the presence of the CBRHA in the locality, participation in
      selection of the agents, acceptance of the agent, and evertalking to CBRHA about
      reproductive health issues were significantly higher in successful than in weak
      program areas [OR(95% CI) = 2.32 (1.74, 3.08), 3.28 (1.22, 9.27), 6.65 (3.59,
      12.43), and 5.05 (3.22, 7.96), respectively]. In multiple logistic regression
      analysis awareness of presence of CBRHA in the village, acceptance of the CBRHA,
      and having had discussion with CBRHA maintained significant associations with
      type of community-based reproductive health program (successful/weak). Focus
      Group Discussions and Key Informant Interviews revealed better involvement of
      community leaders and health workers in the process of selecting and supervising
      CBRHA in successful areas compared to weak areas. The sustainability score of the
      Community-Based Reproductive Health Program (CBRHP) graded by the program
      coordinators was 2.92 out of 5. Acceptance of the CBRHAs, communication of the
      agents with community members, level of Support to the agents, better involvement
      of community representatives in the selection process were found to be the major
      factors affecting CBRHP. Overall sustainability of the CBRHP was low which calls
      for an urgent action.

PMID- 20690291
TI  - Extracellular calcium and magnesium in preeclampsia and eclampsia.
AB  - The cause of preeclampsia remains unknown and calcium and magnesium supplement
      are being suggested as means of prevention. The objective of this study was to
      assess magnesium and calcium in the plasma and cerebrospinal fluid of Nigerian
      women with preeclampsia and eclampsia. Setting was University of Benin Teaching
      Hospital, in Nigeria. It was a cross-sectional study comprising of eleven
      patients and twenty-three controls. The mean, standard deviation and Standard
      Error of Mean (SEM) were calculated. Student 't' test method was applied. Plasma
      calcium was significantly lower in patients than controls (9.2 +/- 1.02 Vs 9.98
      +/- 0.87mg/dl, P 0.043) "t" test. The CSF calcium and magnesium levels were lower
      in patients than controls, (5.66 +/- 1.22 vs 6.67 +/- 1.15 mg/ dl, P 0.043 and
      1.75 +/- 0.56 vs 1.91 +/- 0.19 mg/dl, P 0. < 0.0001) respectively. There is
      extracellular calcium and magnesium reduction in patients with preeclampsia and
      eclampsia. This reduction may have a cause and effect relationship with these
      disorders.

PMID- 20690292
TI  - Heparin and aspirin in pregnant Sudanese women with recurrent miscarriage
      associated with antiphospholipid antibodies.
AB  - This was a prospective clinical trial conducted at Khartoum Fertility Center,
      during the period June 2002 to February 2005 to investigate the efficacy of
      unfractionated heparin and low-dose aspirin as prophylaxis against pregnancy loss
      in 58 pregnant Sudanese women with recurrent (> or = 3) miscarriages associated
      with antiphospholipid syndrome (APS). Three (5.1%) patients had early
      miscarriages, three (5.1%) patients developed pre-eclamptic toxaemia and forty
      seven (81%) of the 58 patients had cesarean delivery. Forty-seven (81%) women had
      live births and 8 (13.8%) had preterm deliveries. Eight (13.8%) of the neonates
      were admitted to the intensive care unit for various reasons. There were 6
      (10.3%) perinatal deaths, all of them were due to prematurity. None of the
      patients developed thromboembolic episode. There was no maternal death. The rate
      of live birth in this study was consistent with the previous reports. This was a
      none controlled study; thus controlled clinical trials using low molecular weight
      heparin are urgently needed.

PMID- 20690293
TI  - Findings from an HIV/AIDS programme for young women in two Nigerian cities: a
      short report.
AB  - This short report describes the findings from an HIV/AIDS programme for young
      women that was held in two Nigerian cities. Very little information is available
      on interventions that address the needs of young Nigerian women; a population
      that represents a high incidence and prevalence of HIV and AIDS. Responses were
      elicited from the programme participants through the use of pre- and post-test
      questionnaires, with a view to identifying effective health education strategies
      for the prevention of sexually transmitted infections including HIV/AIDS among
      young Nigerian women. Outcomes revealed low knowledge levels, poor attitudes and
      misconceptions about HIV/AIDS as well as widespread stigma. This indicates a
      continual need for the design and implementation of a comprehensive and
      culturally appropriate HIV/AIDS and sexual health program for young women in
      Nigeria which meets their needs.

PMID- 20690294
TI  - Spontaneous uterine rupture during pregnancy: case report and review of
      literature.
AB  - Rupture of a gravid uterus is a surgical emergency. Predisposing factors include
      a scarred uterus. Spontaneous rupture of an unscarred uterus during pregnancy is
      a rare occurrence. We hereby present the case of a spontaneous complete uterine
      rupture at a gestational age of 34 weeks in a 35 year old patient. The case was
      managed at the University Teaching Hospital of Yaounde (Cameroon). She had past
      history of two uterine curettages. She presented with abdominal pain of sudden
      onset. After ultrasound scan, uterine rupture was diagnosed and an emergency
      laparotomy done. The entire amniotic sac was found in the peritoneal cavity with
      a rupture of the uterine fundus. Spontaneous uterine rupture occurs when there is
      an upper segment uterine scar. This case report shows that past history of
      curettage is a risk factor for the presence of uterine scar.

PMID- 20690295
TI  - Intestinal obstruction from an adhesion band mimicking peritonitis due to a
      complicated induced unsafe abortion: a case report.
AB  - Miss E.N. a 19-year old nullipara presented at the Accidents and Emergency unit
      of the Ebonyi State University Teaching Hospital (EBSUTH), Abakaliki on the
      17/5/06 with symptoms and signs of peritonitis from possible uterine and bowel
      perforation secondary to induced unsafe abortion. At surgery, it was discovered
      that her problem was due to mechanical small bowel obstruction from adhesion band
      following appendicectomy two years previously. The case highlights the
      similarities of its presentation to some of the complications of induced unsafe
      abortion.

PMID- 20690296
TI  - Population and individual health: the two faces of Janus.

PMID- 20690297
TI  - Aspirin for primary prevention: yes or no?
AB  - AIM: To assess benefit versus harm of aspirin for cardiovascular disease (CVD)
      primary prevention by age group, gender and risk category and to interpret these
      results in light of current New Zealand CVD risk assessment and management
      guidelines. METHODS: Rates of benefit (avoided vascular events) and harm
      (additional major extracranial bleeds) for each gender and age group were
      calculated from data from the six randomised controlled trials included in the
      Anti-Thrombotic Trialists' (ATT) Collaboration meta-analysis. These rates were
      applied to CVD risk categories to calculate the net benefit or net harm likely to
      occur from the use of aspirin in primary prevention of CVD as monotherapy and
      when added to lipid and blood pressure-loweringtherapies. RESULTS: Benefits of
      aspirin monotherapy outweigh the harms for both men and women aged up to 80 years
      with calculated five-year CVD risk >15% in primary prevention. Harm may outweigh
      benefit for primary prevention for those over 80 years. For men 70-79 years the
      benefit of aspirin in primary prevention is marginal when added to lipid and
      blood pressure-lowering therapies. DISCUSSION: The recent ATT Collaboration meta
      analysis has raised doubts about the relative safety of aspirin in primary
      prevention of CVD. However, modelling by risk category and age group suggests
      that current guidelines are justified in recommending aspirin for primary
      prevention of CVD in those with five-year CVD risk > or = 15% up to the age of 80
      years. For men 70-79, consider lipid and blood pressure-lowering therapies first
      then reassess whether aspirin adds additional net benefit.

PMID- 20690298
TI  - What resources do Auckland general practitioners use for answering immediate
      clinical questions and for lifelong learning?
AB  - INTRODUCTION: General practitioners need to search for evidence to remain up-to
      date with knowl edge and to answer clinical questions that arise during
      consultations. In the past their main sources of information have been via
      colleagues and books. AIM: To determine the resources Auckland GPs use to answer
      clinical questions and to maintain lifelong learning. METHODS: One hundred
      questionnaires were mailed to Auckland GPs. There were 33 replies (33% response
      rate). From this sample 10 were chosen at random and all agreed to be interviewed
      (100% response rate). RESULTS: All participants were using Internet resources to
      obtain answers to clinical questions. Colleagues were also important for
      answering immediate questions, but not for future requirements. There is possibly
      less use of paper book resources. The websites were used to obtain knowledge now
      and for future need, while paper books were only used for answering immediate
      questions. DISCUSSION: The use of websites may be increasing in general practice
      for both immediate knowledge requirements and for lifelong learning. Colleagues
      are still a source of answers to immediate clinical questions, but textbooks may
      be less used. Empiric data are needed to monitor changes in answering clinical
      questions and the issue of lifelong learning requires more research.

PMID- 20690299
TI  - Causes of excess hospitalizations among Pacific peoples in New Zealand:
      implications for primary care.
AB  - INTRODUCTION: Pacific people suffer disproportionately poorer health and reduced
      life expectancy at birth compared to the total New Zealand population. AIM: To
      assess causes of excess morbidity in the Pacific population, and identify lesser
      known or previously unknown causes which require further investigation. METHODS:
      We obtained public hospital discharge data from July 2000 to December 2002. The
      population data were from the 2001 Census. Standardised discharge ratios were
      calculated to compare Pacific peoples with the total New Zealand population.
      RESULTS: Pacific peoples were six times more likely to have a diagnosis of
      cardiomyopathy and gout, and four to five times of rheumatic fever, gastric
      ulcer, systemic lupus erythematosus (SLE), and diabetes. Respiratory diseases,
      skin abscesses, heart failure, cataracts, cerebral infarction and chronic renal
      failure were also significant causes of excess morbidity. Unexpected causes of
      excess morbidity included candidiasis, excess vomiting in pregnancy (hyperemesis
      gravidarum) and pterygium. DISCUSSION: The magnitude of established causes of
      excess morbidity among Pacific peoples were similar to our findings. Other causes
      of excess morbidity are less widely known, or are identified here for the first
      time. These are systemic lupus erythematosus, hyperemesis gravidarum,
      cardiomyopathy, gastric ulcer, candidiasis and pterygium. The findings draw
      attention to specific causes of excess morbidity in Pacific communities where
      effective interventions are available in primary care, and where further research
      may identify preventive or curative interventions.

PMID- 20690300
TI  - GP practice variation in hospitalisation rates: a study of partnership health
      enrolled patients.
AB  - AIM: This project aims to provide information to support the planning and
      implementation of strategies to reduce hospitalisation. It examines variations in
      hospital discharge rates between practice populations and the use of special
      general practice access funding. METHODS: Practice enrolment data for 345 254
      patients enrolled with 102 Partnership Health Primary Health Organisation (PHO)
      general practices were sent to New Zealand Health Information Service. Data
      linked to the patient National Health Index (NHI) relating to hospital discharges
      were attached to the practice enrolment data for the two years ending June 2007
      and returned to the researchers with the NHI numbers encrypted. Total discharges
      were 127426. The data were analysed for rates of hospital discharges for
      different population groups and by general practice. RESULTS: There is a
      substantial variation in hospital discharge rates between general practices, but
      this is only partly accounted for by practice population characteristics.
      Furthermore while there is a strong social gradient in European admissions, this
      is much less true for Maori. There was also a wide variation between practices in
      the uptake of High Use Health Cards, special funding for frequent attenders at
      general practices and 'Care Plus' funding for patients with chronic conditions.
      Practice deprivation, ethnicity and age only explained a minor part of this
      variation. DISCUSSION: The high rate of unexplained practice variation in chronic
      care management and hospitalisation rates, especially for Maori, is of concern.
      Further investigation of the causes of such variability is needed as afirst step
      in reducing hospitalisation.

PMID- 20690301
TI  - Modifying the PACIC to assess provision of chronic illness care: an exploratory
      study with primary health care nurses.
AB  - INTRODUCTION: In line with Wagner's Chronic Care Model, the Patient Assessment of
      Chronic Illness Care (PACIC) has been developed to evaluate chronic illness care
      delivery from the patient's perspective. Modification of the instrument to assess
      the same aspects of care delivery from the health practitioner's perspective
      would enable individual practitioners to evaluate their own provision of self
      management support, and would also enable a more direct comparison between care
      provided and care received within the chronic illness context. AIM: To explore
      the potential of a modified PACIC instrument to assess individual health
      practitioners' delivery of care to chronic illness patients with a sample of
      primary health care nurses. METHODS: Seventy-seven primary care nurses completed
      the modified PACIC, reworded to ask about care provision rather than receipt of
      care. An additional seven cultural sensitivity items were included, as were
      questions about the suitability of the types of chronic illness care and who
      should be providing the care. RESULTS: The modified PACIC items appear to be
      appropriate for use with health practitioners. Agreement that the types of care
      described in the PACIC should be provided was almost unanimous, and the
      predominant view was that self-management support should be provided by both
      nurses and doctors. Mean scale scores were higher than those generally reported
      from studies using the PACIC. DISCUSSION: The results of this first evaluation of
      a modified PACIC suggest that the original items plus the cultural sensitivity
      items can be used to assess self-management support by individual health
      practitioners.

PMID- 20690302
TI  - Providing and receiving self-management support for chronic illness: patients'
      and health practitioners' assessments.
AB  - INTRODUCTION: Providing care for people with chronic illness is a major issue for
      health practitioners around the world, especially as populations age. Encouraging
      self-management is beneficial in terms of relieving the burden on the health
      system and promoting better health and adherence to medication and advice amongst
      this group. AIM: To measure the level of self-management support being provided
      to and received by people living with chronic illness in a District Health Board
      (DHB) region. METHODS: Self-report questionnaires (PACIC) were completed by 341
      people living with chronic illness to measure the self-management support they
      receive from general practitioners and nurses. A modified version of the PACIC
      was used with 12 GPs and 77 primary health nurses in the same region to assess
      the provision of self-management support. RESULTS: Patients' assessments suggest
      that they are receiving intermittent self-management support for their chronic
      illness. A comparison of ratings of different health practitioners revealed that
      nurses were reported to be providing support more consistently than GPs. The
      health practitioners rated themselves as providing self-management support more
      often than the patients reported receiving it. Many clinicians also suggested
      that not all forms of support are appropriate for everyone, suggesting the need
      to tailor support to the individual. DISCUSSION: Chronic illness support needs to
      be considered within the context ofthe individual and to be embedded in an
      ongoing relationship between the person and the provider. Findings highlightthe
      benefits of a multidisciplinaryteam approach to self-management support and
      education in chronic illness care.

PMID- 20690303
TI  - Ever decreasing circles: terminal illness, empowerment and decision-making.
AB  - INTRODUCTION: Empowerment is the personal and political processes patients go
      through to enhance and restore their sense of dignity and self-worth. However,
      there is much rhetoric surrounding nurses facilitating patients' daily choices
      and enabling empowerment. Furthermore, there is frequently an imbalance of power
      sharing, with the patient often obliged to do what the health professional wants
      them to do. METHOD: This phenomenological study describes the lived experience of
      patients attending an outpatient clinic of a community hospice. A qualitative
      study using Max van Manen's phenomenological hermeneutic method was conducted to
      explore issues surrounding empowerment and daily decision-making with terminally
      ill patients. The participants' stories became a stimulus for learning about the
      complexities of autonomy and empowerment. It also engendered reflection and
      analysis of issues related to power and control inequities in current nursing
      practices. FINDINGS: The results revealed not only the themes of chaoticum,
      contracting worlds and capitulation, but that health professionals should be
      mindful of the level of control they exert. Within the palliative care setting
      they need to become partners in care, enhancing another person's potential for
      autonomous choice. CONCLUSION: Empowerment must not be somethingthat simply
      occurs from within, nor can it be done by another. Intentional efforts by health
      professionals must enable terminally ill people to be able to stay enlivened and
      connected with a modicum of autonomy and empowerment over daily decisions, no
      matter how mundane or monumental they might be.

PMID- 20690304
TI  - Seeing patients first: creating an opportunity for practice nurse care?
AB  - INTRODUCTION: Practice nurses see patients in both a planned (i.e., scheduled
      appointment) and an unplanned (i.e., opportunistic) manner. This study aimed to
      investigate how often and why New Zealand practice nurses see patients prior to
      the general practitioner and whether they organise their care to support
      unplanned, opportunistic activity. METHOD: National postal survey from a random
      sample of 500 general practices, requesting a response from one nurse per
      practice. Semi-structured telephone interviews with a purposeful sample of
      respondents. FINDINGS: Responses came from 225 nurses (51% of practices confirmed
      to be eligible). Nearly all (92%) said their work role was the same as that of
      others in their practice. Only 13% of nurses routinely saw patients prior to the
      doctor, while 24% would choose to do so it they could, and 65% thought it
      important. Positive and negative aspects of seeing patients first are presented.
      Constraints included time, their role assisting practice workflow and perceptions
      of patient expectations. Few organised their work to create opportunities for
      lifestyle interventions. CONCLUSION: The current working environment of practice
      nurses in New Zealand does not readily support them routinely seeing patients
      before the general practitioner. We suggest this is a lost opportunity for
      patient-centred preventive care.

PMID- 20690305
TI  - What influences practice nurses to participate in post-registration education?
AB  - INTRODUCTION: There is a need for educated primary health nurses to develop their
      practice, educational and career pathways in response to opportunities emerging
      from the Primary Health Care Strategy (PHCS). This study aimed to explore the
      opportunities and constraints encountered by practice nurses when participating
      in post-registration education. METHODS: This study used exploratory qualitative
      design, incorporating focus group interviews with 16 practice nurses employed by
      Pegasus Health, Christchurch. Qualitative thematic analysis used a general
      inductive approach. FINDINGS: Seven key themes emerged, including motivation to
      learn, enablers for learning and challenges to accessing education. Practice
      nurses also described their changing roles with clients and their vision for
      practice nursing in the future. CONCLUSION: This study considered accessibility
      of post-registration education for practice nurses and the extent to which they
      are embracing these opportunities in order to meet their practice needs. The PHCS
      states that primary health care nursing is crucial to its implementation.
      Successful expansion of primary health care nursing roles rests on the
      development of educational qualifications and skills, as well as career
      frameworks. It is envisaged that, with strong leadership and research skills
      resulting from professional development, practice nurses will be more able to
      reduce health inequalities. Study findings indicate that practice nurses are
      rising to the challenge of expanding their roles and engaging in post
      registration education. They are more likely to pursue this if constraints are
      minimised and support increased. Currently practice nurses make significant
      contributions to primary health care and have the potential for an even greater
      contribution in the future.

PMID- 20690306
TI  - Are unexplained vaginal symptoms associated with psychosocial distress? A pilot
      investigation.
AB  - AIM: Vaginal complaints cannot be definitively diagnosed in approximately one
      third of women. We sought to determine if women without a diagnosis had higher
      levels of psychiatric disorders. METHODS: This was an observational study in an
      urban family practice clinic. Prior to seeing a clinician, women with vaginal
      complaints completed the Patient Health Questionnaire (PHQ); symptoms were
      measured by the Vaginal Complaints Scale (VCS). Patients were then examined and
      treated by a family physician. At one and two weeks' time patients were contacted
      by phone regarding symptom resolution and clinical outcomes. RESULTS: We enrolled
      47 patients; one patient was excluded. A diagnosis was made in 36. Eighteen had
      bacterial vaginosis, 16 had candida, three trichomonas, two HSV, one chlamydia;
      there were eight dual diagnoses. PHQ diagnoses were slightly less common in women
      without an identified cause for their symptoms. We obtained follow-up data from
      45 subjects at one week and 34 subjects at two weeks' time. At two weeks' follow
      up, 97% of subjects had complete resolution or improvement of their symptoms.
      Symptom improvement was equivalent among women with a diagnosis and those
      without. We estimate 180 subjects would be needed to detect a clinically
      meaningful difference in PHQ diagnoses. DISCUSSION: Our pilot study did not find
      an association between psychiatric diagnoses made by the PHQ and unexplained
      vaginal symptoms. Nearly all patients experienced rapid resolution of symptoms
      irrespective of whether a diagnosis had been made or not. These findings are
      limited primarily by the small sample size.

PMID- 20690307
TI  - New Zealand general practice should adopt population-based screening for
      attention deficit hyperactivity disorder (ADHD): yes.

PMID- 20690308
TI  - Ginkgo.

PMID- 20690309
TI  - A whanau ora approach to health care for Maori.

PMID- 20690310
TI  - Too much information?

PMID- 20690311
TI  - PSA screening reply.

PMID- 20690312
TI  - Conflict of interest in peer-reviewed medical journals: the World Association of
      Medical Editors (WAME) position on a challenging problem.

PMID- 20690313
TI  - The few, the proud...
AB  - While free-standing hospitals may be more vulnerable under health reform, some
      are vowing to go it alone. And 2009 saw an improvement in finances for stand
      alone hospitals. For some, it's a matter of flexibility and desire for local
      autonomy. "Having a meaningful level of local control is something we'll always
      value," says Steve Carlson, a hospital CEO in Missoula, Mont.

PMID- 20690314
TI  - Keeping a close eye on health plans. New regulations give consumers recourse
      against rescissions, denials.

PMID- 20690315
TI  - Not such a pastoral setting. Rural-specific issues contribute to high suicide
      rates.

PMID- 20690316
TI  - Largest hospitals. Ranked by total number of staffed beds.

PMID- 20690317
TI  - The Chicago Breathe Project: a regional approach to improving education on asthma
      inhalers for resident physicians and minority patients.
AB  - BACKGROUND: Asthma affects minority citizens in Chicago disproportionately.
      Policy changes introducing hydrofluroalkane (HFA) inhalers may worsen already
      existing health disparities related to asthma. AIMS: To teach internal medicine
      residents about the transition to HFAs so they can better counsel their patients
      on asthma self-management. To provide minority community members with interactive
      educational sessions. SETTING: Internal medicine residents at 5 Chicago programs.
      Community workshops in primarily Spanish-speaking (Cicero) Latino population and
      a primarily African American population from the south side of Chicago. PROGRAM
      DESCRIPTION: The Chicago Breathe Project provides residents with education and
      tools necessary to counsel patients with asthma on inhaler use and provides
      minority community members with interactive educational sessions on asthma and
      inhaler use. PROGRAM EVALUATION: Eleven workshops were held across 5 academic
      institutions, with a total of 161 residents. Resident knowledge regarding HFA
      inhalers improved dramatically (5% pre vs. 91% post, p < .001). Six months post
      education, residents were more likely to assess inhaler technique (44% vs. 11%, p
      = .046) and discuss new HFA inhalers (69% vs. 24%, p = .011) with their asthma
      patients. Community members provided feedback after the workshops that they would
      come again, found the session helpful ,and enjoyed the session. DISCUSSION: The
      Chicago Breathe Project resulted in improved resident knowledge and skill on
      inhaler use during HFA transition. Regional educational approaches targeting
      internal medicine residencies in urban areas may be helpful to address future
      changes in chronic disease management. This training can be taken into minority
      communities to provide high-quality interactive educational workshops directly to
      patients and their families.

PMID- 20690318
TI  - Disparities between asthma management and insurance type among children.
AB  - Asthma is a chronic illness among children. Minority children may be vulnerable
      to asthma complications since more than half are from households that are poor or
      near poor, and some have no health insurance. Asthma management plans are
      important for the long-term treatment of asthma and beneficial for self
      management. This study analyzed insurance type and the relationship between
      having an asthma management plan among children across all races with asthma.
      This study utilized the 2002 and 2003 National Health Interview Survey. Findings
      showed that whites were significantly more likely than Non-Hispanic blacks and
      Hispanics to have an asthma management plan (OR, 1.66; p = .0031). In this study,
      children who reported Children's Health insurance Program (CHIP) coverage were
      twice as likely to have an asthma management plan (OR, 2.67; p = .0004).
      Mandating all insurers to provide an asthma management plan to children with
      asthma may reduce the race-based inequities and differences in asthma management
      plan status.

PMID- 20690319
TI  - Complementary and alternative medical practice: self-care preferred vs.
      practitioner-based care among patients with asthma.
AB  - BACKGROUND: Interest in disease self-management has increased as the US
      population ages, as health care costs skyrocket, and as more evidence is gathered
      on the etiologic basis of most chronic diseases. This study uses National Health
      Interview Survey (NHIS) data to analyze the association between asthma episode
      during the past 12 months and patterns of complementary and alternative medicine
      (CAM) use within the same period among adults, controlling for comorbid
      conditions. METHODS: Using questions taken from the adult sample questionnaire
      and the Alternative Supplement of the 2002 NHIS, responses of those ever having
      asthma (N=3327) were analyzed in this cross-sectional, correlational study. The
      chi2 test of independence was used to examine the relationships between
      experiencing an asthma episode in the past year, coexisting comorbidity, and the
      use of self-care based CAM compared to practitioner-based CAM. RESULTS: Overall
      CAM use differed significantly by asthma status, with 49% of those with asthma
      episodes using CAM compared with 42% of those who did not have an episode in the
      past year. Self-care based therapies were more likely to be used than
      practitioner-based therapies by individuals with single comorbid condition
      compared to those with 2 or more comorbidities. CONCLUSION: Although this study
      supports previous work indicating that disease severity--in this instance, asthma
      within the past year--is significantly associated with CAM use, it did not
      support studies showing greater CAM use in the presence of a greater number of
      comorbidities, suggesting that disease burden is a limiting factor when it comes
      to self-care based CAM use.

PMID- 20690320
TI  - Identifying chronic obstructive pulmonary disease in primary care of urban
      underserved patients: tools, applications, and challenges.
AB  - Among urban low-income and minority patients with compromised access or low
      adherence to primary care, exacerbations of unrecognized but symptomatic moderate
      to severe chronic obstructive pulmonary disease (COPD) cause avoidable emergency
      room visits and hospitalizations. Detection and management of COPD before a first
      exacerbation reduces morbidity and disability, forestalls cardiorespiratory
      complications, improves health-related quality of life, and reduces health care
      costs. However, current efforts in ascertainment and care of COPD have
      insufficiently improved outcomes in underserved groups. Effective COPD care
      requires access to detection and management resources: screening tools to
      identify who may have COPD, spirometric diagnosis, smoking cessation assistance,
      vaccinations, stage-appropriate pharmacotherapy, and rehabilitation. This article
      describes recent advances in tools suitable for assisting COPD identification in
      primary care practices and discusses their applications in urban underserved
      populations. The validated COPD Population Screener is readily understood by
      patients, self-scored, available online (www.copdscreener.com), and usable in
      community outreach as well as primary care settings. Symptom-based risk
      stratification with a validated questionnaire provides a rational trigger
      targeting limited spirometry resources to patients most likely to have COPD. Case
      finding is the first step of COPD management to reduce its individual and public
      health burden.

PMID- 20690321
TI  - African American primary care physicians' perceptions and practices regarding
      smoking cessation therapy.
AB  - African American smokers (34% of males and 23% of females) need formal
      interventions to assist them in quitting smoking, a major method of preventing
      premature mortality from smoking-related illnesses. The purpose of this study was
      to examine African American primary care physicians' perceptions and practices
      regarding smoking cessation counseling. A national random sample (n=202) of
      primary care physicians was asked about their perceptions and practices regarding
      smoking cessation therapy. Most (89%) placed themselves in the maintenance stage
      for asking their patients about their smoking status and regularly documented the
      smoking status of their patients (70%). Most physicians did not comply with all
      of the components of the U.S. Public Health Services' smoking cessation
      guidelines (e.g., 5 A's and 5 R's). The component most often implemented of the 5
      A's was to "advise" patients to quit (89%), and "arrange" followup was the least
      frequently (60%) used component. Perceived barriers to engaging in smoking
      cessation interventions were time (38%) and patients not interested in quitting
      (19%). Although physicians used many of the steps in the 5 A's and 5 R's, they
      were far less compliant in recommending nicotine replacement therapy, prescribing
      pharmacotherapy, and providing support and/or follow-up for patients who were
      willing to quit smoking. Physicians need more academic preparation in providing
      smoking cessation counseling since few received such training in medical school
      (31%) or during their residency programs (18%).

PMID- 20690322
TI  - Comparison of health perceptions and health status in African Americans and
      Caucasians.
AB  - PURPOSE: This study was designed to compare the health perceptions of adults
      based on race (African American and Caucasian) and gender in the southern United
      States to determine if health perception contributed to health disparity between
      African Americans and Caucasians. METHODS: A between-groups design was used in
      this study where African Americans and Caucasians completed an extensive health
      questionnaire and were compared for health perceptions and self-reported health
      status differences. RESULTS: Fewer African Americans (p < .05; males, 55.8%;
      females, 68%) perceived their health to be good to excellent compared with
      Caucasians (males, 76.6%; females, 77.1%) and more had been diagnosed with 1 or
      more chronic diseases. Yet, more than three-quarters of all groups thought that
      their health care provider shared with them good to excellent information about
      their health, and 75.0% of the African American males and 71.5% of the Caucasian
      males and more than 62.0% of the African American and Caucasian females stated
      that medication cost was not a reason they did not take prescribed medications.
      CONCLUSIONS: Health perceptions of African Americans are often not consistent
      with their actual health, and this is especially true for African American males.
      Their perceptions appear to influence the value they place on health behaviors
      which may result in a reduced health status.

PMID- 20690323
TI  - Evaluation of telemetry utilization, policy, and outcomes in an inner-city
      academic medical center.
AB  - OBJECTIVE: To evaluate the appropriateness and intermediate outcomes of telemetry
      admissions. METHODS: We abstracted demographic and clinical data from records of
      all new telemetry admissions during a 2-month period. To determine
      appropriateness, 2 authors classified patients using the American College of
      Cardiology (ACC) guidelines and our telemetry policy. Other utilization and
      outcome measures were assessed. Agreement between both guidelines was computed
      (kappa coefficient). Categorical group covariates were compared using chi2 test.
      Variations in telemetry length of stay (LOS) were compared using Mann-Whitney and
      Kruskal-Wallis tests. LOS predictors were ascertained by multiple regression
      analysis. RESULTS: Of the 120 patients, appropriate admission was 81.6% (ACC
      criteria) and 83% by our criteria. Guidelines interrater reliability was .89
      (kappa). Telemetry events incidence was 33.3%, with 5.8% major and 27.5% minor.
      LOS was longer among major than minor events group(7.8 vs. 3.4 days, p = .01).
      Type of telemetry event was a predictor of LOS (p = .0001). The occurrence of a
      major telemetry event was associated with cardiology consultation (p = .03).
      CONCLUSIONS: Appropriate telemetry admission was observed in more than 80% of
      cases. Our telemetry policy had very good agreement with standard guideline.
      However, the low rate of major telemetry events in all patient groups suggests
      current guidelines might have considerable limitations.

PMID- 20690324
TI  - Academic medical centers and underserved communities: modern complexities of an
      enduring relationship.
AB  - BACKGROUND: Most private academic medical centers are located in underserved
      areas, yet fiscal pressures have led many to struggle with balancing their
      commitment to surrounding communities with other missions. OBJECTIVE: To explore
      stakeholders' views regarding the ethical, legal, and financial obligations of
      private academic medical centers to their surrounding neighborhoods. DESIGN,
      PARTICIPANTS, AND MEASURES: QualitatiVe analysis of key informant interviews
      during 2008 with medical students, faculty and community physicians,
      administrators, and community health leaders at a large urban academic medical
      center. Grounded theory was used to iteratively review, code, and revise a
      taxonomy of themes, with abstraction of illustrative quotes. RESULTS: Nineteen in
      depth interviews were conducted. All respondents believed academic medical
      centers have an obligation to their surrounding communities but characterized the
      extent of this obigation in a variety of ways. Respondents disagreed about how
      the core mission of an academic center should be defined, although many
      recognized the tripartite mission, conflict centered on the balance that should
      be sought between research and clinical care. A majority of interviewees
      expressed frustration with the nation's current health care system. Many provided
      unprompted recommendations regarding how academic medical centers might engage
      their underserved communities, including conducting formal needs analyses,
      promoting ongoing dialogue, and using information technology to bridge the
      provision of clinical care in community and academic settings. CONCLUSIONS: These
      data provide enriching perspectives from stakeholders regarding this enduring yet
      evolving relationship. The diversity of views illustrates one of the challenges
      that will accompany health care reform impacting academic medical centers and
      their surrounding, often underserved, communities.

PMID- 20690326
TI  - Racial/ethnic patterns of uptake of colorectal screening, National Health
      Interview Survey 2000-2008.
AB  - BACKGROUND: Lower access and/or utilization of colorectal screening are thought
      to be major contributors to the higher proportion of cancers among African
      Americans and Hispanics that are diagnosed at advanced stages of disease and the
      poorer outcomes observed among Hispanics and African Americans compared with non
      Hispanic whites. We examine rates of initiation, utilization of specific
      screening modalities, adherence tocolorectal screening guidelines, and rate of
      uptake of colonoscopy among age-eligible African Americans, Hispanics and non
      Hispanic whites. METHODS: Data on 46145 African American, Hispanic, and non
      Hispanic white survey respondents to the 2000 and 2005 Cancer Control Modules and
      the 2003 and 2008 Sample Adult Cores of the National Health Interview Surveys are
      examined in these analyses. RESULTS: There was a modest increase in the
      initiation of colorectal screening among non-Hispanic whites, only and
      racial/ethnic disparities colorectal screening utilization persisted. The
      proportion of respondents for whom colonoscopy was the most complete guideline
      consistent exam received increased over time, while use of other modalities
      decreased among all racial/ethnic groups. CONCLUSION: More effort must be made to
      increase colorectal screening among the U.S. population in general but
      particularly among racial/ethnic minority populations. With the increased
      attention on prevention, there is also a need to increase knowledge of the
      strengths and limitations of specific screening modalities and the need to
      receive screening exams within recommended time intervals among both patients and
      providers making screening recommendations.

PMID- 20690325
TI  - The intersection of violence, substance use, depression, and STDs: testing of a
      syndemic pattern among patients attending an urban STD clinic.
AB  - OBJECTIVES: High rates of psychosocial and health problems have been identified
      among patients attending sexually transmitted disease (STD) clinics, who are
      disproportionately urban, have low income, and are racial/ethnic minorities. This
      study sought to determine whether these problems co-occurred and whether they
      indicated the presence of a syndemic. METHODS: Patients (N = 1557, 46% female,
      64% African American) attending an urban STD clinic completed a computerized
      survey assessing childhood sexual abuse (CSA), depressive symptoms, binge
      drinking, marijuana use, intimate partner violence (IPV), and sexual risk
      behavior. Medical records were reviewed to determine incident STD diagnosis.
      RESULTS: The psychosocial and health problems were interrelated. Endorsing more
      psychosocial problems was associated with a greater likelihood of having multiple
      sexual partners and STD diagnosis. Interactions between CSA and marijuana use and
      between CSA and IPV predicted STD diagnosis. CONCLUSIONS: Numerous psychosocial
      and health problems co-occur among urban STD clinic patients. There was some
      evidence of a syngergistic relationship (i.e., a syndemic) between these
      conditions, resulting in worsened sexual health outcomes. Health care needs to be
      multidisciplinary to address the multiple psychosocial and health problems faced
      by STD clinic patients. Research needs to identify factors that may underlie
      these comorbid conditions.

PMID- 20690327
TI  - The correlation between patient comprehension of their reason for hospital
      admission and overall patient satisfaction in the emergency department.
AB  - OBJECTIVES: (1) To determine the patient's comprehension of the reasons for
      admission in the emergency department and (2) to examine what, if any,
      correlation there is between patients' understanding and satisfaction with care.
      METHODS: Using a convenience sample over a 6-month period, patients from an
      urban, level 1 adult and pediatric trauma center were interviewed by research
      fellows in a patient care area. A total of 287 patients were given the Emergency
      Department Quality Study (EDQS) survey in either English or Spanish. Only
      patients 18 years or older, who were able to consent, spoke English or Spanish,
      and were medically stable were included in the study. The study was approved by
      the institutional review board. An analysis of variance was used to determine if
      any significant difference exists between patient understanding and satisfaction
      with care. In order to determine which of these variables could predict patient
      satisfaction levels, a log linear regression was used. RESULTS: The majority
      (90%) of patients rated their care as good to excellent, and 78% of them did
      understand why they were being admitted. A total of 22%, however, did not
      understand their test results and the cause for their being admitted to the
      hospital. There was a significant negative finding among the patient not having
      an understanding of tests, reason for admission, returning to the emergency
      department for care, and their overall patient satisfaction. CONCLUSIONS:
      Successful communication between doctors and patients around the reasons for
      admission and test results can be an important predictor of patient satisfaction.
      Medical information not communicated in an understandable way to patients can
      lead to lower levels of patient satisfaction.

PMID- 20690328
TI  - Corneal ulcers in a tertiary hospital in Africa.
AB  - PURPOSE: To study the clinical features of corneal ulcers in a tertiary hospital
      in Africa. METHODS: This is a retrospective review of the medical records of 82
      consecutive corneal ulcer patients who presented to the eye clinic of Enugu State
      University of Science and Technology (ESUT) Teaching Hospital Parklane, Enugu,
      Nigeria, in 2008. Data entry and analysis was done using SPSS version 15.0.
      RESULTS: The 82 consecutive patients comprised 38 males (36.3%) and 44 females
      (53.7%). Fifty-five (71.4%) presented with visual acuity in the affected eye of
      less than 3/60. After treatment, the vision improved in 21 eyes (32.3% of the
      total), remained the same in 34 eyes (52.3%), and deteriorated in 4 eyes (6.2%);
      6 eyes (9.2%) had to be eviscerated. Forty-three eyes (52.4%) had antecedent
      trauma: Only 5 patients (6.1%) presented to the hospital within 24 hours of
      trauma or onset of symptoms. Thirty-eight patients (47.6%) sought treatment from
      patent medicine dealers prior to coming to the hospital, while 16 (19.5%)
      admitted use of traditional eye medication. CONCLUSION: Trauma is a major risk
      factor for corneal ulcer in developing countries. Vision is often poor after
      treatment, making corneal ulcer a major cause of corneal blindness. Patients
      commonly seek help from the wrong source and only present to the hospital when
      these have failed.

PMID- 20690329
TI  - A man with pain and a large nevus on his thigh.

PMID- 20690330
TI  - Diabetes in sub-Saharan Africa: health care perspectives, challenges, and the
      economic burden of disease.
AB  - The growing incidence of diabetes mellitus in the world is a widespread concern.
      While there has been improvement in the epidemiology and management of the
      disease in the developed world, the same cannot be said in sub-Saharan Africa.
      The disease is getting less attention as is the funding that it merits compared
      to communicable diseases. Type 2 diabetes is becoming more prevalent due to
      rising rates of obesity, physical inactivity, and urbanization. In contrast to
      the developed world, where the majority of the people with diabetes are over the
      age of 60 years, the sub-Saharan Africa diabetic population is in the
      economically productive age group of 30 to 45 years. The late diagnosis of
      diabetes in this region, coupled with inequalities in accessing care, leads to
      early presentations of diabetic complications. The health care delivery agenda is
      overwhelmed by poverty, as such diabetes management costs have to compete with
      other health issues such as antiretroviral drugs for HIV/ AIDS, tuberculosis
      treatment, and malarial control programs. There is an urgent need to place
      diabetes on the national health agenda in sub-Saharan Africa and ensure that this
      agenda is properly positioned and integrated into the health policies and
      strategies.

PMID- 20690332
TI  - Improving men's health benefits us all.

PMID- 20690333
TI  - Developing men's awareness of health issues.

PMID- 20690331
TI  - Inferior vena cava thrombus in renal primitive neuroectodermal tumor is not rare.

PMID- 20690334
TI  - Gender differences in general practice utilisation in New Zealand.
AB  - INTRODUCTION: This paper aims to examine gender differences in general practice
      utilisation in New Zealand. METHODS: The dataforthis research came from 10 506
      visit records gathered from 246 general practitioners (GPs) who took part in the
      National Primary Medical Care Survey (NatMedCa), a nationally representative,
      multistage, probability sample survey of GPs and patient visits conducted in
      2001/2002. The number of visits to a general practice in the last 12 months among
      those patients who visited the GP at least once during the past 12 months was
      used as the outcome variable. Poisson regression was used for analysis. RESULTS:
      Women were more likely than men to visit a GP over the last 12 months (IRR =
      1.13; 95% CI: 1.03-1.24). We also found significant female excess in utilisation
      of GP services even after excluding gynaecological and obstetric conditions and
      across all age groups. Asian were 39% less likely than European women to visit a
      GP (IRR = 0.61; 95% CI: 0.43-0.85); a result that was not reflected in men's
      utilisation of GP services. In addition, we found that women visiting GPs were
      39% more likely to have reported life-threatening' problems as compared to 'self
      limiting' problems (IRR = 1.39; 95% CI: 1.00-1.94). CONCLUSION: Our results do
      not support the body of literature that suggests that women's excess in service
      use can largely be attributed to gynaecological and obstetrical conditions or
      that the female excess in visits is focussed in the childbearing years. Ethnicity
      and the severity of a problem contributed significantly to explaining women's,
      but not men's, utilisation of GPs.

PMID- 20690335
TI  - Getting back the missing men of Aotearoa: declining gender inequality in NZ life
      expectancy.
AB  - INTRODUCTION: Men's health is of increasing concern to policy makers worldwide.
      Although women generally live significantly longer than men, the difference in
      life expectancy in many countries is now narrowing. AIM: To document the trend in
      sex differences in New Zealand (NZ) life expectancy at birth (LEB) over the last
      decades and to determine disease patterns which account for it. METHODS:
      Decomposition of sex differences in LEB by age and cause for the periods 1980-82,
      1985-87, 1990-92,1995-97, 2000-02, and 2005-06, using registered deaths and model
      life tables. RESULTS: Sex differences in LEB increased from 1951 to peak in 1976
      before narrowing again. In 2006 they reached almost exactly the level they were
      at 55 years earlier. Changes in relative mortality from ischaemic heart disease
      (IHD) and to a lesser extent accidents, respiratory disease and other circulatory
      causes, brought about the recent decline in gender survival disparities. IHD
      continues to be a significant cause of gender inequality, but cancers have now
      become a major component of the sex difference in LEB. DISCUSSION: NZ's
      experience mirrors closely that of other developed countries in pattern,
      timingand the age-cause composition of the trend in gender survival disparities.
      Thus differences in the timing of taking up smoking, found to explain a
      substantial portion of the trend elsewhere, were probably also important in NZ,
      but improvements in medical outcomes for smokers also must have played a
      significant role. Primary care practitioners will continue to reduce gender
      survival disparities by workingto ensure a high uptake of services such as
      screening for colorectal cancer, one of many diseases responsible for lower male
      life expectancy.

PMID- 20690336
TI  - Human papillomavirus and papillomavirus vaccines: knowledge, attitudes and
      intentions of general practitioners and practice nurses in Christchurch.
AB  - INTRODUCTION: General practitioners (GP) and practice nurses (PN) perform the
      majority of cervical screening in Christchurch and will have a key role in
      influencing uptake of human papillomavirus (HPV) immunisation. AIM: To assess and
      compare GP and PN knowledge about HPV disease, attitudes concerning adolescent
      sexual behaviour and intentions to recommend HPV immunisation. METHODS: A self
      administered, anonymous questionnaire was distributed to GPs and PNs in
      Christchurch, New Zealand who attended peer-led small group meetings hosted by
      Pegasus Health Independent Provider Association in May 2008. RESULTS:
      Participation rate was 39%. Overall, 94% of respondents knew that HPV
      immunisation will not replace cervical cancer screening; 73% knew that HPV is the
      cause of cervical cancer; 48% knew that most HPV infections will clear without
      medical treatment; 20% correctly reported that anogenital warts are not cervical
      cancer precursors. More GPs reported comfort discussing sexual behaviour with
      adolescents than PNs (p < .008). While 95% of participants intend to recommend
      immunisation for 13-15-year-old girls, PNs were more likely than GPs to recommend
      HPV immunisation to older female adolescents and more often indicated that HPV
      vaccination may lead to risky sexual behaviour (p < .0001). DISCUSSION: This is
      the first New Zealand study to assess primary care knowledge and attitudes about
      HPV and HPV immunisations. The results are encouraging, provide a baseline for
      future research and may guide the development of training materials for GPs and
      PNs.

PMID- 20690337
TI  - The cost of immunising at the general practice level.
AB  - INTRODUCTION: Childhood immunisation is one of the most cost-effective activities
      in health care. However, New Zealand (NZ) has failed to achieve national coverage
      targets. NZ general practice is the primary site of service delivery and is
      funded on a fee-for-service basis for delivery of immunisation events. AIM: To
      determine the average cost to a general practice of delivering childhood
      immunisation events and to develop a cost model for the typical practice.
      METHODS: A purposeful selection of 24 diverse practices provided data via
      questionnaires and a daily log over a week. Costs were modelled using activity
      based costing. RESULTS: The mean time spent on an immunisation activity was 23.8
      minutes, with 90.7% of all staff time provided by practice nurses. Only 2% of the
      total time recorded was spent on childhood immunisation opportunistic activities.
      Practice nurses spent 15% of their total work time on immunisation activity. The
      mean estimated cost per vaccination event was $25.90; however, there was
      considerable variability across practices. A 'typical practice' model was
      developed to better understand costs at different levels of activity.
      CONCLUSIONS: The current level of immunisation benefit subsidy is considerably
      lower than the cost of a standard vaccination event, although there is wide
      variability across practices. The costs of delivery exceeding the subsidy may be
      one reason why there is an apparently small amount of time spent on extra
      opportunistic activities and a barrier to increasing efforts to raise
      immunisation rates.

PMID- 20690338
TI  - Variation in Partnership Health general practice enrolment data related to need
      and hospital and national records on ethnicity.
AB  - AIM: To compare enrolment data for ethnicity and deprivation and other
      classifications in Partnership Health Primary Health Organisation (PHO) general
      practices with the National Health Index (NHI) data set and hospital discharge
      data and to analyse use of special access funding. METHODS: NHI-linked practice
      data were obtained through Partnership Health and sent directly to New Zealand
      Health Information Service (NZHIS). The database was linked with the hospital
      discharge data for the two years ending June 2007, with the NHIs encrypted. Data
      were analysed for a range of variables and relationships especially related to
      ethnicity. RESULTS: Data was obtained from atotal of 345 247 patients in 103
      practices. Practices varied widely in their data completion including ethnicity,
      the latter being unavailable in 7.2% of patients. Ethnicity recording in
      Partnership Health practice was substantially more complete than national NHI
      records. Maori in the hospital records was 6.1% compared with 7.0% in the
      Partnership Health records relating to discharged patients (p < .001). Practice
      use of special access funding varied widely and was unrelated to need.
      DISCUSSION: Despite substantial practice database development, findings point to
      the need for further collaborative and innovative strategies to improve data
      recording. Issues needing to be addressed nationally include regular updating and
      correction of the national NHI set from PHO records. PHO data could, with
      improvements, become the basis for District Health Board databases. The findings
      support the current national review of the use of special access funding which
      appears to be seriously inequitable and inefficient.

PMID- 20690339
TI  - New Zealand men's health care: are we meeting the needs of men in general
      practice?
AB  - AIM: To describe and compare how men and health professionals perceive men's
      health and health care. METHOD: A qualitative study with an inductive thematic
      analysis of transcripts from three sequential sets of focus groups. The first set
      included groups totalling 21 general practitioners and 10 practice nurses; the
      second set with a group of 12 men under 25 years and a group of 10 older men over
      35 years; and the third set with the original groups of health professionals.
      Datasets were analysed individually, sequentially and comparatively for men's and
      health professionals' beliefs about health and health care. RESULTS: In the
      initial focus groups, health professionals reported system, structural, and
      attitudinal barriers inhibiting men attending general practice. Men reported
      broad-based health beliefs and, despite reluctance to seek formal health care,
      men value general practice care and want recognition of their preferred
      consulting styles. In the final focus groups, researchers fed-back analysis of
      the health professionals' and men's focus group data with the aim of encouraging
      further focussed men's health initiatives. However, there was a general lack of
      enthusiasm from health professionals to do more than what was being done already.
      CONCLUSIONS: Despite men and health professionals recognising the importance of
      men's health, there is general unwillingness on the part of both men and health
      professionals, for different reasons, to engage with men's health care in general
      practice. Understanding how men view health and health care delivery has the
      potential to inform alternative approaches in general practice care.

PMID- 20690340
TI  - Do invitations to attend Well Man Checks result in increased male health
      screening in primary health care?
AB  - BACKGROUND AND CONTEXT: Male health outcomes lag behind those of women in many
      areas. Male utilisation of primary health care and uptake of preventative health
      care is relatively lower. Our question was: will inviting males who have not
      received recent health screening nor attended the practice frequently result in a
      higher rate of male health checks? ASSESSMENT OF PROBLEM: An auditable uniform
      classification 'Well Man Check' was established and education sessions on the
      importance of increasing male health care were held for all clinical staff.
      Recording of Well Man Check was audited for time periods prior to and after
      mailing out invitations to attend a Well Man Check. Thirty cases were reviewed to
      see if previously unrecognised health risks or symptomatic problems were
      detected. RESULTS:  BOTTOM LINE: inviting males to attend for a Well Man Check
      almost triples the number of recorded Well Man Checks, and does not reduce the
      number of opportunistic Well Man Checks carried out. A range of problems and
      health risks requiring intervention or follow-up were detected. STRATEGIES FOR
      IMPROVEMENT: Further mail-outs to wider age ranges and ongoing discussion of
      results to stimulate ongoing interest amongst clinical staff is planned. LESSONS:
      Mail-out invitations do increase recorded Well Man Checks both within the age
      group mailed to, and also for males outside that age group.

PMID- 20690341
TI  - More allopurinol is needed to get gout patients < 0.36 mmol/l: a gout audit in
      the form of a before-after trial.
AB  - AIM: To establish a benchmark for gout control using the proportion of patients
      with serum uric acid (SUA) < 0.36 mmol/L, assess patients' understanding of their
      preventive medication and trial a mail and phone intervention to improve gout
      control. METHODS: Patients clinically diagnosed with gout and baseline SUAs were
      identified in two South Auckland practices. A mail and phone intervention was
      introduced aimed at improving the control of gout. Intervention #1 took place in
      one practice over three months. Intervention #2 occurred in the other practice
      four to 16 months following baseline. RESULTS: No significant change in SUA from
      intervention #1 after three months. The second intervention by mail and phone
      resulted in improvement in SUA levels with a greater proportion of those with SUA
      < 0.36 mmol/L and the difference in means statistically significant (p = 0.039
      two-tailed paired t-test). Benchmarking for usual care was established at 38-43%
      SUA < 0.36 level. It was possible to increase from 38% to 50%. Issues relating to
      gout identified included lack of understanding of the need for long-term
      allopurinol and diagnosis and management for patients for whom English is not
      their first language. STRATEGIES FOR IMPROVEMENT: 1. Community workers who speak
      Pacific languages may assist GPs in communicating to non-English speaking
      patients. 2. Alternative diagnoses should be considered in symptomatic patients
      with prolonged normouricaemia. 3. GPs should gradually introduce allopurinol
      after acute gout attacks, emphasising importance of prophylaxis. 4. A campaign to
      inform patients about benefits of allopurinol should be considered. 5. A simple
      one keystroke audit is needed for gout audit and benchmarking. 6. GP guidelines
      for gout diagnosis and management should be available.

PMID- 20690342
TI  - New Zealand should introduce population screening for prostate cancer using PSA
      testing: yes.

PMID- 20690343
TI  - Saw palmetto. Serenoa repens. Also known as Serenoa serrulata, Sabal serrulata
      and the dwarf palm.

PMID- 20690344
TI  - Strategies to address disparities in access to care must be multidimensional.

PMID- 20690345
TI  - Who shall decide: telling the truth and avoiding the law--patient consent in the
      millennium.

PMID- 20690346
TI  - Cardiovascular disease risk profile tools and new zealand--the best way forward?

PMID- 20690347
TI  - Values transparency and inter-professional communication.

PMID- 20690348
TI  - Nurse and medical (general) practitioners.

PMID- 20690349
TI  - Nurse and medical (general) practitioners.

PMID- 20690350
TI  - Battlefield acupuncture.

PMID- 20690351
TI  - Should we give aspirins and statins to the elderly?

PMID- 20690352
TI  - A look at the workforce, the common cold and a handy insert on drug interactions:
      something for everyone.

PMID- 20690353
TI  - Primary care workforce planning: what's happened to the 'Logan' report?

PMID- 20690354
TI  - Primary mental health care: service delivery and the impact on the workforce.

PMID- 20690355
TI  - Position statement: Primary health care nursing.

PMID- 20690356
TI  - Trends for primary health care nurses.

PMID- 20690357
TI  - Community physiotherapy workforce issues.

PMID- 20690358
TI  - The workforce shortage disadvantages those in greatest need.

PMID- 20690359
TI  - Doctors and romance: not only of interest to Mills and Boon readers.
AB  - INTRODUCTION: Internationally there is a growing demand for health services.
      Skilled health workers, including doctors, have a high degree of international
      mobility and New Zealand (NZ) stands out internationally in terms of the
      significant flows of doctors in and out of the country. Through changes in
      training of doctors in NZ and migration flows, there have been major shifts in
      the composition of the medical workforce in NZ since the mid-1980s. AIM: Studies
      of the changing nature of the medical workforce often focus on gender and
      migration separately as well as only considering doctors as individuals. The aim
      of this exploratory study is to examine the living arrangements of doctors, the
      composition of migrant doctors who are coming to NZ, and to understand the
      educational and employment status of the partners of doctors. METHODS: This study
      is a descriptive analysis primarily using census data from 1986 through to 2006
      and immigration data collected by the Department of Labour. RESULTS: Half of the
      female medical doctors approved for residence through the Skilled/Business stream
      migrated independently, while for male doctors less than athird came to NZ
      independently. Male migrant doctors were more likely to be partnered. Census data
      showed that people with medical backgrounds tend to partner with each other.
      However, these relationships are changing, as more women become doctors. In 1986
      about 14% of male doctors had a nurse or midwife as a partner and nearly 9% had a
      doctor partner. By 2006 the proportion of partners of male doctors who were also
      doctors had risen to 16%, higher than the 9% who were nurses. For female doctors
      the changes are more dramatic. In 1986, 42% of female doctors in relationships
      had a doctor as a partner. By 2006, female doctors had increased substantially,
      but the percentage with a doctor partner had dropped to under athird. Well
      qualified couples where one or both are doctors, have a greater propensityto live
      in main urban areas. DISCUSSION: Through official reports and extensive media
      coverage, the NZ public is well aware of local and national doctor shortages.
      There is also awareness, often through personal visits to a GP or hospital, of
      the significant rise in number of female and of foreign-born doctors. The choices
      doctors are making in living arrangements need to be taken into account when
      considering both national and international recruitment of medical staff.
      Researchers and policy makers may need to consider family migration issues more
      than they have in the past for doctors as well as for other migrant groups.

PMID- 20690360
TI  - General practice in urban and rural New Zealand: results of the 2007 RNZCGP
      membership survey.
AB  - INTRODUCTION: The provision of primary health care is an integral part of both a
      country's health system, and of the overall social and economic development of
      its communities. An adequate general practice and primary health care workforce
      is a prerequisite to the provision of good primary health care. Countries with
      stronger primary health care services have better health and much lower health
      costs. This paper reports the results of the RNZCGP's 2007 annual membership
      survey and discusses workforce development in urban and rural New Zealand (NZ).
      METHOD: In 2007, the RNZCGP sent a survey form to all its financial members as
      part of the annual subscriptions mail-out to gather data about College members'
      current working patterns and help construct a longitudinal view of work
      preferences and hours worked per week. RESULTS: The response rate was 59% (1995
      members/participants: 1098 males (55%) and 897 females). More female GPs (86%)
      worked in urban centres than male GPs (83%). NZ European GPs were overrepresented
      (67%) in the South Island when compared to their representation within the total
      population. Numbers of international medical graduates (IMGs) had increased in
      urban centres since 2005. All regions experienced a decrease in self-employed
      GPs. Rural GPs spend more hours per week in general practice than urban GPs.
      CONCLUSION: The GP workforce is an integral part of the NZ primary health care
      workforce, and is currently facing many challenges. Stakeholders need to ensure
      that NZ remains an attractive primary health care environment in order to retain
      NZ-trained GPs and attract IMGs.

PMID- 20690361
TI  - Do scores in the selection process for vocational general practice training
      predict scores in vocational examinations?
AB  - AIM: Selection processes for vocational training are common and are intended to
      predict future examination performance (predictive validity). Comparison of
      selection scores with measures of competence during training can provide
      supporting evidence that both the examination process and selection process are
      valid and reliable. METHOD: Selection interview scores for vocational training in
      general practice were compared to summative examination scores eight months into
      training between 2003 and 2006. RESULTS: A moderately strong correlation
      (Spearman's rho = 0.5) was found between selection interview scores and summative
      examination scores. CONCLUSION: The ability of a selection interview process to
      predict future performance in vocational training is highly dependent on careful
      design of both the assessment of performance and the selection process. The
      selection interview process of the RNZCGP compares well with international data.

PMID- 20690362
TI  - The provision of mental health care by primary health organisations in the
      northern region: barriers and enablers.
AB  - AIM: To identify barriers and enablers to the provision of mental health care by
      Primary Health Organisations (PHOs) in the northern region. METHODS: Information
      was generated from structured interviews with 22 of the 25 PHOs and the four
      District Health Boards (DHBs) in the northern region. RESULTS: Of the 22 PHOs who
      participated in the study, 17 had at least one specific mental health initiative;
      others had up to five initiatives. PHOs that were funded to provide one of the 41
      Ministry of Health mental health pilot projects had more mental health
      initiatives in place. Barriers and enablers to providing mental health care
      occurred in areas such as workforce capacity, funding, infrastructure, and
      limited interest in transfer of care from secondary to primary care. CONCLUSIONS:
      Barriers to providing mental health care within the primary sector include
      stigma, lack of training, communication between sectors, funding and perceptions
      of sector roles. Factors which enable provision of mental health care are
      availability of training, good communication between sectors, use of available
      and new funding mechanisms and community involvement. Further research at the
      practice and practitioner level is necessary to fully understand development of
      mental health care within the primary care sector.

PMID- 20690363
TI  - The Pacific primary health care workforce in New Zealand: what are the needs?
AB  - AIM: To scope future needs of the NZ Pacific primary care workforce. METHOD: Semi
      structured interviews with key informants including Pacific primary care workers
      in both Pacific and mainstream primary health care organisations and managers at
      funding, policy and strategy levels. Qualitative thematic analysis using general
      inductive approach. RESULTS: Thirteen stakeholders interviewed (four males, nine
      females) in 2006. Included both NZ- and Island-born people of Samoan, Tongan,
      Niuean, Fijian and NZ European ethnicities; age 20-65 years. Occupations included
      general practitioner, practice nurse, community worker, Ministry of Health
      official and manager representing mainstream and Pacific-specific organisations.
      Key themes were significant differences in attributes, needs and values between
      'traditional' and contemporary Pacific people; issues regarding recruitment and
      retention of Pacific people into the primary health care workforce; importance of
      cultural appropriateness for Pacific populations utilising mainstream and Pacific
      specific primary care services and both advantages and disadvantages of 'Pacific
      for Pacific' services. CONCLUSION: Interviews demonstrated heterogeneity of
      Pacific population regarding ethnicity, age, duration of NZ residence and degree
      of immersion in their culture and language. Higher rates of mental disorder
      amongst NZ-born Pacific signpost urgent need to address the impact of Western
      values on NZ-born Pacific youth. Pacific population growth means increasing
      demands on health services with Pacific worker shortages across all primary
      health care occupations. However it is not possible for all Pacific people to be
      treated by Pacific organisations and/or by Pacific health workers and services
      should be culturally competent regardless of ethnicity of providers.

PMID- 20690364
TI  - Is intranasal zinc effective and safe for the common cold? A systematic review
      and meta-analysis.
AB  - OBJECTIVE: To systematically review the evidence for effectiveness of intranasal
      zinc used to treat a common cold, and pool the results in a meta-analysis. DATA
      SOURCES: A literature search was undertaken in the Cochrane register of
      controlled trials, MEDLINE and EMBASE databases. Inclusion criteria were
      randomised placebo controlled trials in patients with a common cold. RESULTS:
      Five studies were found. Three were relevant to the issue of treatment of common
      colds with intranasal zinc and the results were combined in meta-analysis. High
      doses of intranasal zinc preparation (2.1 mg zinc/day) were reported in two
      studies to shorten the duration and reduce the symptom severity of common cold in
      healthy adults, when started within 24 to 48 hours of onset of illness. A lower
      dose study (0.044 mg zinc/day) found no benefit in resolution, but did report a
      significant improvement in symptoms at day 1 and day 3. Combining the three
      studies, the relative risk for benefit at day 3 was 0.62 (95% CI 0.18 to 2.19)
      (random effects). There were no studies with children. There were no significant
      harms reported. CONCLUSION: Results from individual trials suggest some benefit
      from zinc for symptoms of a common cold, at least in adults. Poolingthe results
      for symptom relief at day 3, in a conservative meta-analysis, suggests a non
      significant benefit. Unquantified concerns about permanent anosmia followingthe
      use of intranasal zinc may mean that the issues raised will never be
      scientifically resolved.

PMID- 20690365
TI  - The nurse practitioner provides a substantive opportunity for task substitution
      in primary care: yes.

PMID- 20690366
TI  - A recommendation from suspected cancer in primary care: guidance for referral and
      reducing disparities from the NZ Guidelines Group.

PMID- 20690367
TI  - Echinacea.

PMID- 20690368
TI  - Learning to 'see' in the clinician-patient relationship.
AB  - Medical education tends to praise or pay lip-service to the art of observation,
      while systematically teaching the science of technology. To the extent you were
      taught observation skills as clinicians, you may have learned how to listen and
      touch but not usually how to 'see' your patients and yourself. This paper
      considers how to see in the clinician-patient relationship, not merely in an
      optical sense but also to increase your perceptiveness. We suggest 10 strategies
      to enhance your ability to see.

PMID- 20690369
TI  - Clinically important drug-drug interactions and how to manage them.

PMID- 20690370
TI  - In search of true autonomy.
AB  - Patient autonomy is discussed in medical care now both because this is an
      appropriate ethical practice and also as a reaction against the emphasis that was
      placed in the past on the medical profession 'always knowing best'. This article
      examines where our present understanding and practice of the ethical concept of
      autonomy may be flawed. It examines both doctors' and patients' responsibilities
      for this flaw and how they may be rectified.

PMID- 20690371
TI  - Tyneside to New Zealand.

PMID- 20690372
TI  - View from the edge.

PMID- 20690373
TI  - A type of lady's corset? support for older people.
AB  - 'Older people need support.' What sense do older people themselves make of this
      apparently simple statement? Comments drawn from qualitative research underway
      with older New Zealanders highlight the gulf between the language of older people
      and the well-meaning assumptions of primary health care professionals about
      support needs. These thought-provoking vignettes show it is crucial to delicately
      negotiate the ways that support is offered and delivered to people who have long
      achieved the autonomy and self-sufficiency prized in Western societies.

PMID- 20690374
TI  - The dynamic steady state.

PMID- 20690375
TI  - Acupuncture.

PMID- 20690376
TI  - 'How can I help?' may be a risk to rapport.

PMID- 20690378
TI  - Modern epidemics and gifts for humanity.

PMID- 20690377
TI  - The health beliefs of cultural minorities.

PMID- 20690379
TI  - Methamphetamine--what primary care practitioners need to know.

PMID- 20690380
TI  - Are there disparities in care in people with diabetes? A review of care provided
      in general practice.
AB  - AIM: To estimate the prevalence of diabetes by age, gender and ethnicity; to look
      at quality of care and to investigate disparities in care. METHOD: A cross
      sectional study in three practices in Hamilton. A comprehensive register was
      generated by identifying patients with diabetes through queries on the practices'
      computer system looking for diagnosis codes for diabetes, prescription of
      hypoglycaemic agents, participation in the 'Get Checked' programme or laboratory
      test for HbA1c. We then compared the glycaemic control and uptake of retinal
      screening in adult patients with Type 2 diabetes. RESULTS: The overall prevalence
      of diabetes in patients aged 20 years or older was 1221/26 096 (4.7%). Eighty
      percent had attended for a 'Get Checked' annual review in the last 12 months.
      After adjusting for age, we found that Maori, males and those diagnosed more than
      five years ago were at increased risk of having unsatisfactory glycaemic control.
      Maori or Asian patients and women appeared less likely to have accessed retinal
      screening in the last two years. DISCUSSION: Computerised records including
      diagnostic codes and prescriptions in general practices can be used to develop
      comprehensive diabetes registers. Whilst this study shows that high levels of
      annual review can be achieved in patients with diabetes, the next challenge is to
      tackle the disparities in uptake of services such as retinal screening or the
      achievement of intermediate outcomes such as good glycaemic control.

PMID- 20690381
TI  - Use of aspirin and statins for cardiovascular risk reduction in New Zealand: the
      residential care story.
AB  - INTRODUCTION: Cardiovascular disease (CVD) is one of the leading causes of
      morbidity and mortality for older New Zealanders. Medication prescribing for
      secondary prevention of cardiovascular events in residential care is unknown and
      prescribing patterns for aspirin and statins by general practitioners (GPs) in
      residential care facilities in Auckland, New Zealand are reported here. METHODS:
      A representative sample of residential care facilities, all residents over age 65
      years and their GPs in one district health board region in Auckland were
      recruited. Prescribing and medical records were audited by a trained nurse and
      medications coded into classes according to a standardised process. Diagnoses
      from summary sheets and hospital letters were recorded. Descriptive statistics
      were used to show variability in proportion of residents prescribed aspirin and
      statins. RESULTS: Of a total of 24 facilities approached, 14 consented to
      participate (58%); 537 residents (88% of eligible) agreed to participate and 533
      completed the study. Residents took on average 8.3 (standard deviation 2.4)
      medications. On average 2.64 (range 1-6) GPs serviced each facility with eight
      GPs working in more than one facility. On average 54% of residents with
      documented CVD were prescribed aspirin and 31% of those with CVD and/or
      dyslipidaemia were prescribed statins. Variability between prescribers and
      facilities was high. DISCUSSION: Prescribing in residential care does not appear
      to be guidelines-based. The reasons for this are unknown. Ongoing social debate
      about the role of prevention for older people and interventions for GPs and
      residential care facilities may impact prescribing rates.

PMID- 20690382
TI  - What makes Care Plus effective in a provincial Primary Health Organisation?
      Perceptions of primary care workers.
AB  - INTRODUCTION: Care Plus is a New Zealand chronic care initiative. It provides
      funding for extra primary care visits for patients with chronic diseases and aims
      to improve chronic care management, primary health care team work and reduce
      inequalities in health care. This mixed methodology study aimed to explore
      characteristics within practices that may contribute to improved clinical
      outcomes for Care Plus. METHODS: A focus group interview was conducted with a
      group of health professionals involved in Care Plus in a North Island Primary
      Health Organisation (PHO). Participants were selected because of their 'expert
      status'. Interview analysis used a general inductive approach. A questionnaire
      was sent to all practice nurses to determine prevalence of characteristics
      derived from the focus group. FINDINGS: Seven primary care workers involved in
      Care Plus participated in a focus group from which three major themes emerged:
      nursing factors, practice organisation factors and general practitioner (GP)
      factors. Sub-themes identified as patient-centredness, assertive follow-up,
      nursing knowledge, referral to other health professionals, dedicated appointment
      times, long consultation time, low cost, GP commitment and teamwork were all
      considered to be characteristics that could lead to improved clinical outcomes.
      Questionnaire responses from 18 practice nurses suggest that GPs are under
      involved with Care Plus. DISCUSSION: Patients with chronic conditions have
      complex needs. Care Plus is a nationwide initiative providing funding for chronic
      care. Some characteristics of nurses, practice organisation and GPs may lead to
      improved clinical outcomes in Care Plus. A number of these characteristics are
      supported in the literature.

PMID- 20690383
TI  - Perspectives of general practitioners towards evaluation and treatment of
      cardiovascular diseases among older people.
AB  - INTRODUCTION: Risk of cardiovascular disease (CVD) events increases with age.
      With treatment, individuals with highest risk accrue greater absolute risk
      reduction. New Zealand's CVD guidelines provide no upper age limit for risk
      assessment. Guidance for treating those over 75 years is limited. Little is known
      about GPs' attitudes regarding assessing and managing cardiovascular risk among
      older people. METHODS: A 39-item questionnaire including three cases representing
      various risk was developed and administered to 500 GPs randomly selected from a
      registry. RESULTS: Of the GPs, 379 were eligible; 86 (22%) responded to the
      questionnaire. Most were male (57%), between 40 and 59 years of age (74%), of
      European ethnicity (57%), had a medical degree from NZ (60%), and had been
      practising for at least 10 years (98%). Respondents were less likely to assess
      risk with increasing patient age and more likely to manage risk according to
      individual risk factors, rather than absolute risk. Marked variation occurred in
      intent to assess risk for a patient aged 78 years, according to living
      environment, co-morbidity, and functional status. In general, respondents
      indicated that they would usually assess risk for a 78-year-old community
      dwelling patient without dementia but not for such a patient living in
      residential care or with dementia. DISCUSSION: This is New Zealand's first report
      of GPs' perspectives about assessing and managing CVD risk for older patients.
      Findings are consistent with international studies. More support and training in
      lifestyle assessment is needed, as well as clearer guidance for assessing and
      managing risk among older patients.

PMID- 20690384
TI  - Barriers to accessing specialist care for older people with chronic obstructive
      pulmonary disease in rural New Zealand.
AB  - INTRODUCTION: Access to health care for people living in rural areas presents
      many challenges. For people who live with chronic obstructive pulmonary disease
      (COPD), the ability to access specialist health services facilitates improved
      health outcomes, however many barriers to accessing specialist health care have
      been identified. This paper reports on the challenges people living with COPD in
      rural New Zealand (NZ) face in accessing specialist health care services.
      METHODS: Nine people living with COPD in a small NZ rural town were interviewed
      in 2007. FINDINGS: Data analysis, using a general inductive approach found that
      difficulties with transportation, physical access, communication and finances
      collectively added up to significant barriers to accessing specialist care for
      this group of people. CONCLUSION: The findings raise questions about the model of
      care needed to improve health care for rural people with COPD. Collaborative
      multidisciplinary teams with specialist respiratory nurses working in the
      community are proposed to improve care coordination and improve communication for
      this group of people.

PMID- 20690385
TI  - The reality of subclinical hypothyroidism in general practice.
AB  - INTRODUCTION: Subclinical hypothyroidism (SCH) is common, reported to affect 4
      10% of the adult population. Recommendations for treatment of SCH are
      contentious, with protagonists even disagreeing over the rationale for medical
      intervention. How general practitioners (GPs) manage patients with elevated
      thyroid stimulating hormone (TSH) and normal thyroid hormone results are unknown.
      This study aimed to explore how GPs think about diagnosing and managing SCH.
      METHODS: A qualitative study using focus groups conducted between December 2007
      and March 2008 to understand how GPs perceive SCH and their diagnostic and
      management process. FINDINGS: Thirteen GPs in three focus groups in Waikato, New
      Zealand participated. There is wide variability in how GPs perceive SCH and their
      knowledge of the disease. A patient-centred approach to diagnosis and management
      was commonly reported. Consideration of overt pathology and medicolegal issues
      also influenced perceptions of SCH, but lack of evidence regarding outcomes of
      treatment made such issues complex. CONCLUSION: SCH remains a complex entity
      because of ambiguity regarding symptoms, uncertainty regarding prognosis and
      variation in advice regarding treatment. This complexity is reflected in the
      disparate responses by GPs to the diagnosis and management of SCH.

PMID- 20690386
TI  - Why don't patients with diagnosed diabetes attend a free 'Get Checked' annual
      review?
AB  - INTRODUCTION: A key strategy for improving the management of patients with
      diabetes is the provision of a free annual review 'Get Checked'. Although it is
      known that certain patients do not attend these free reviews, little is known
      about the barriers. METHODS: A group of patients with diabetes who had not
      attended an annual review in the previous two years were identified and sent
      questionnaires asking about the barriers to attending. Non-respondents where
      followed up with a telephone call. Barriers were thematically analysed. FINDINGS:
      26/68 patients identified patients responded (38%). Key issues identified
      included difficulty with transport, conflict with work and lack of motivation.
      There were differences in responses between Maori and non-Maori. CONCLUSION:
      Recommendations include more emphasis in recognising Maori tikanga (culture),
      more flexible provision of services to allow working patients to attend and
      increased emphasis on reminders for patients.

PMID- 20690387
TI  - Cardiovascular risk assessment: audit findings from a nurse clinic--a quality
      improvement initiative.
AB  - BACKGROUND AND CONTEXT: Evidence has shown the effectiveness of risk factor
      management in reducing mortality and morbidity from cardiovascular disease (CVD).
      An audit of a nurse CVD risk assessment programme undertaken between November
      2005 and December 2008 in a Northland general practice. METHOD: A retrospective
      audit of CVD risk assessment with data for the first entry of 621 patients
      collected exclusively from PREDICT-CVDTM, along with subsequent data collected
      from 320 of these patients who had a subsequent assessment recorded at an
      interval ranging from six months to three years (18 month average). RESULTS: Of
      the eligible population (71%) with an initial CVD risk assessment, 430 (69.2%)
      had afive-year absolute risk less than 15%, with 84 (13.5%) having a risk greater
      than 15% and having not had a cardiovascular event. Of the patients with a follow
      up CVD risk assessment, 34 showed improvement. Medication prescribing for
      patients with absolute CVD risk greater than 15% increased from 71% to 86% for
      anti-platelet medication and for lipid lowering medication from 65% to 72% in the
      audit period. STRATEGIES FOR IMPROVEMENT: The recently available 'heart health'
      trajectory tool will help patients become more aware of risks that are
      modifiable, together with community support to engage more patients in the nurse
      CVD prevention programme. Further medication audits to monitor prescribing
      trends. LESSONS: Patients who showed an improvement in CVD risk had an
      improvement in one or more modifiable risk factors and became actively involved
      in making changes to their health.

PMID- 20690388
TI  - A polypill is the solution to the pharmacological management of cardiovascular
      risk: yes.

PMID- 20690389
TI  - Devil's claw (Harpagophytum procumbens). Also known as 'grapple plant' or 'wood
      spider'.

PMID- 20690390
TI  - Non-financial barriers to primary health care services for Maori.

PMID- 20690391
TI  - Fresh eyes for chronic care management.

PMID- 20690392
TI  - Making people be healthy.
AB  - How are we supposed to decide the rights and wrongs of banning smoking in bars,
      restricting adverts for junk food, nagging people into being screened for
      cancers, or banning the sale of party pills? The aim of this paper is to think
      through the political ethics of trying to make people healthier through
      influencing or restricting their choices. This paper covers: (1) Paternalism.
      What it is, what it assumes. (2) The place of health in well-being, and how this
      makes paternalism problematic. (3) The mistakes people make in acting in their
      own interests, and the implications for pro-health paternalism. (4) Autonomy
      objections to paternalism. The paper (5) finishes on a note of hope, by
      commending the currently fashionable libertarian paternalism: trying to have
      one's carrot cake and eat it too. A persistent theme is that thinking sensibly
      about making people healthier needs subtlety, not broad, ringing declarations.

PMID- 20690393
TI  - Hopeful for return to the glory days.

PMID- 20690394
TI  - High praise for the Journal of Primary Health Care.

PMID- 20690395
TI  - Relevant research: will this confirm or change my practice?

PMID- 20690396
TI  - Impact on quit attempts of mailed general practitioner 'brief advice' letters
      plus nicotine replacement therapy vouchers.
AB  - AIM: To test whether a personalised letter from general practitioners advising
      their patients who are smokers to quit, together with an exchange card for one
      month of nicotine gum, prompts them to make quit attempts, is acceptable and
      feasible. METHODS: Non-randomised before-after ecological study involving general
      practices in Auckland, New Zealand. Personalised letters with exchange cards for
      four weeks of nicotine gum were sent to 831 patients within a single Auckland
      health board area who were recorded as current smokers on their general
      practitioners files. The comparison group was the population in another Auckland
      health board area. We measured calls to Quitline and vouchers redeemed at
      pharmacies from both areas before and after the intervention. Follow-up surveys
      of recipients and general practitioners assessed acceptability. RESULTS: Quitline
      calls from baseline to the end of the intervention from the intervention district
      compared with a comparison district were not significantly higher (5%, 95% CI -2
      12%, p = 0.195), but nicotine replacement therapy (NRT) voucher redemptions were
      significantly higher (9%, 95% CI 3-16%, p = .005). Almost 9% of the exchange
      cards were redeemed for NRT. Despite initial difficulties in accurately
      identifying smokers from their records, responding GPs found the strategy very
      acceptable. DISCUSSION: The strategy shows potential as a simple way to increase
      the number of smokers making supported quit attempts through primary care. In the
      light of the urgent need to increase cessation rates, a randomised trial of this
      promising approach is warranted.

PMID- 20690397
TI  - Relationship of root canal treatment to C-reactive protein as an inflammatory
      marker for cardiovascular disease.
AB  - INTRODUCTION: Periodontal disease and elevated C-reactive protein (CRP) tests
      both are positively correlated with cardiovascular disease (CVD) in many studies.
      Some health practitioners have concerns that root canal treatment may provide a
      source for inflammation and hence increase the risk for CVD. AIM: To explore the
      relationship between CRP as a marker of inflammation and presence and number of
      root canal treatments in primary care patients. METHODS: Cross-sectional
      questionnaire about dental care followed by a blood test for serum CRP in
      patients from two New Zealand urban family practices. RESULTS: One hundred and 34
      patients participated. The study showed no significant association between CRP
      and root canal treatment on multivariate analysis controlling for socioeconomic
      status, age, gender and smoking. The CRP level for those with > or = 3 root
      treated teeth was 1.68 while the level for those with < 3 was 2.36, but the p
      value was not statistically significant (p = 0.198). Age, missing teeth and
      smoking were all significantly related to CRP levels so the sample has biological
      validity. DISCUSSION: Root canal treatment was not associated with higher CRP
      levels. The CRP levels were non-significantly lower in those with higher numbers
      of root-treated teeth. While there are a number of potential biases in this
      paper, the dataset appears to be biologically valid and consistent with known
      facts. These findings do not support the hypothesis that root canal treatment is
      associated with higher levels of inflammation. At this point patients should not
      consider having their root canal teeth removed.

PMID- 20690398
TI  - Weight loss in head and neck cancer patients little noticed in general practice.
AB  - INTRODUCTION: In head and neck cancer patients, weight loss increases morbidity
      and mortality, and decreases treatment tolerance and quality of life. Early
      nutritional intervention has beneficial effects on these factors. AIM: We
      observed patients' weight courses after specialists' care and surveyed nutrition
      related documentation by general practitioners (GPs). METHODS: From a Head and
      Neck Oncology Centre (HNOC) study, 68 patients were asked to participate in an
      extended general practice cohort. Twenty-six patients participated in the
      prospective three-monthly weight measurements during the year after HNOC care. We
      extracted nutritional information contained in referral letters (n = 24) and
      medical records from the year before referral (n = 45) and after HNOC care (n =
      26). An impaired nutritional status was assigned to weight loss > or = 10% within
      six months or Body Mass Index (BMI) < 18.5 kg/m2 and 'at risk' to weight loss >
      or = 5% but < 10% within six months. RESULTS: Three (12%) participants were
      nutritionally impaired and two (8%) were deemed 'at risk'. Although GPs suspected
      a (pre-) malignancy in 11 cases (46%), only two (8%) documented weight loss or
      BMI and four (17%) nutrition-related complaints in their referral letters.
      Medical records more often contained information on nutrition-related complaints
      and tube feeding later in the disease course, as opposed to concern over weight
      loss or BMI. DISCUSSION: Therefore, we call for nutritional management in general
      practice, by urging practitioners to assess patients' nutritional status
      throughout the disease course and intervene if necessary. The passing on of
      related information in case of referral promotes continuity of care.

PMID- 20690399
TI  - Use of the inhaled corticosteroid to bronchodilator ratio in an audit of the
      treatment of asthma in an academic family medicine residency programme.
AB  - INTRODUCTION: Asthma affects around 5% of the United States population, with 50%
      having uncontrolled symptoms. AIM: To improve asthma care by seeing if the
      inhaled corticosteroid to bronchodilator ratio (RATIO) is associated with asthma
      control and if non-clinical factors were associated with adherence to asthma
      guidelines. METHOD: A retrospective study using University of Oklahoma-Tulsa,
      School of Community Medicine Family Medicine Clinic electronic medical records of
      a random sample of 49 patients with asthma who were seen at least twice from July
      2003 through June 2007 and did not have a diagnosis of chronic obstructive
      pulmonary disease or exercise-induced asthma. RESULTS: The RATIO for those
      prescribed corticosteroid inhalers was directly related to the actual step of
      asthma care (STEP) but inversely related to the number of prednisone courses
      prescribed per year (R2 =.30, p = 0.0012). The difference between the actual STEP
      and ideal STEP (had corticosteroid inhalers been prescribed for all the months in
      the study) was directly related to the percent of available salbutamol
      (albuterol) inhalersthat non-clinicians refilled and inversely related to the
      actual STEP (R2 = .45, p = 1.8 x 10(-5)). The available corticosteroid inhalers
      prescribed was directly related to the actual STEP and inversely related to the
      number of comorbid diagnoses addressed at the last asthma visit (R2 = .70, p =
      5.8 x 10(-10)). DISCUSSION: Efforts to both limit salbutamol medications,
      especially by non-clinicians, and simultaneously prescribe appropriate amounts of
      inhaled corticosteroids, through a dedicated asthma visit, should improve asthma
      control. A higher RATIO implies better asthma control.

PMID- 20690400
TI  - A raised thyroid stimulating hormone result--a 12-month follow-up study in
      general practice.
AB  - INTRODUCTION: Subclinical hypothyroidism (SCH) is common in older patients. AIM:
      To review the management of patients identified with a raised thyroid stimulating
      hormone (TSH) result in a 12-month period and compare this to current guidelines
      from the New Zealand Best Practice Advocacy Centre (BPAC). METHODS: We collected
      laboratory data on thyroid function tests (TFTs) that were reported between
      December 2005 and November 2006 from two general practices with an adult
      population of approximately 21 000. Data were collected on symptoms,
      investigations, thyroid medication, family history and comorbidities. We used chi
      squared tests to compare findings by age, gender and ethnicity. RESULTS: Older
      women of European descent were more likely to be to have initial results
      suggesting SCH. The number of follow-up tests ranged from 0 to 5 tests in a 12
      month period. Forty-eight percent of individuals did not have any follow-up
      investigations. Seventy-three percent of FT4 tests taken are requested
      concurrently with TSH. Of those who had a repeat TSH test, just over 40% had a
      result within the reference interval. Twenty-eight percent had two TSH results
      consistent with SCH. Thirty-five percent of patients with antibody results were
      positive. The most commonly-recorded symptoms were tiredness and weight gain.
      DISCUSSION: We found inconsistencies in the management of SCH which were not
      related to patient characteristics such as age, gender or ethnicity. Further
      research is needed to determine if SCH is associated with increased morbidity and
      to provide a clear rationale for management of patients with SCH.

PMID- 20690401
TI  - Validation of quality of life and functional measures for older people for
      telephone administration.
AB  - INTRODUCTION: Quality of life (QoL) and functional status are important aspects
      of health especially for older people. Efficient and valid ways of measuring
      older people's health is of great importance. AIM: This project aims to establish
      the reliability of use of (1) a quality of life measure, the WHOQOL-BREF, and (2)
      a functional measure, the Nottingham Extended Activities of Daily Living scale
      (NEADL), for use over the telephone. METHODS: With ethical approval, patients
      over age 75 years (65 years if Maori) have been enrolled in the BRIGHT trial; a
      randomised controlled trial testing a practice-based screening initiative to
      prevent disability. Participants with possible disability, defined as being
      unable to get in and out of the car or take hot drinks from one room to another,
      completed a telephone interview including the two measures. Seventy participants
      repeated the two measures during a face-to-face interview within three months.
      RESULTS: Both WHOQOL-BREF and NEADL scores for the two forms of administration
      produced high Pearson correlation coefficients. There was good agreement for the
      WHOQOL-BREF as shown by th Bland-Altman graphs; however there was a tendency of a
      greater negative difference the greater the average score became (higher level of
      function) for the NEADL. DISCUSSION: This study shows that telephone interviews
      can generally provide a valid method to assess the quality of life and function
      in older people.

PMID- 20690402
TI  - Barriers experienced by Asians in accessing injury-related services and
      compensations.
AB  - INTRODUCTION: The Accident Compensation Corporation (ACC) administers New
      Zealand's (NZ) accident compensation scheme. Asians in NZ are apparently under
      serviced by ACC and may be experiencing barriers to accessing services. This
      study identifies barriers that Asians in NZ face in accessing ACC's injury
      related services and compensations. METHODS: By utilising a qualitative research
      design, 113 Chinese, Korean, Indian, and South East Asian participants residing
      in Auckland, NZ were recruited through maximum variation and purposive snowball
      sampling. Data were gathered during 2006 through 22 individual in-depth
      interviews and 14 focus group discussions based on semi-structured interview
      schedules. Interviewees included Asian general practitioners, traditional health
      providers, users and non-users of injury-related services, case managers and
      Asian community leaders. Data were analysed using a general inductive approach.
      FINDINGS: Results show that personal/cultural characteristics such as age,
      gender, English language competence, injury-related language competence,
      differing Asian worldviews, and consequent help-seeking behaviours act as
      barriers to accessing services and entitlements. This is exacerbated by
      logistical and environmental factors such as cost, transport, time, inadequate
      interpretation and translation services, as well as institutional barriers such
      as lack of information about services, culturally inappropriate services,
      discriminatory attitudes and employment risks. CONCLUSION: It is evident that
      Asians living in NZ are experiencing several cultural, environmental and
      institutional barriers to accessing ACC services. There is clearly a need for
      more culturally relevant information and injury-related services if Asian
      immigrants' use of such services and entitlements is to be increased.

PMID- 20690403
TI  - Introducing point-of-care testing into a rural hospital setting: thematic
      analysis of interviews with providers.
AB  - INTRODUCTION: Hauora Hokianga Enterprises Trust, an integrated Primary Health
      Organisation (PHO), which provides primary and intermediate/secondary care to a
      remote rural community, introduced point-of-care (POC) testing at Rawene Hospital
      in June 2008. Previously, all laboratory tests were undertaken in Whangarei, with
      a one to three day turn-around for results. This study aimed to identify the
      perceived impact of POC testing on clinicians and the community. METHOD: Face-to
      face interviews were conducted with 13 health professionals working at Rawene
      Hospital. The qualitative data analysis computer programme ATLAS.ti v5.2 was used
      to assist the thematic analysis. FINDINGS: Three overall themes captured the main
      issues with introducing POC testing: (1) POC testing increased clinicians'
      confidence, certainty and assurance in their daily practice; (2) POC testing
      improved diagnostic certainty and this impacted on patients and their
      families/whanau; (3) the challenges associated with POC testing included
      increased workload, pressure to up-skill, over-testing, and continuing
      professional education gaps. CONCLUSION: POC testing is an invaluable
      technological adjunct for improving clinical decisions and culturally safe care
      provided to a remote rural community, but it brings challenges to care providers
      in managing higher workloads and pressures to up-skill. POC testing can improve
      the acute medical care (access and quality) provided to an economically-deprived,
      predominantly Maori, rural community.U

PMID- 20690404
TI  - A special type of 'hard-to-reach' patient: experiences of pregnant women on
      methadone.
AB  - INTRODUCTION: Opiate addicts in New Zealand are a heterogeneous, hard-to-reach
      group with illicit drug activity as their common characteristic. This project
      investigated the experience of a specific hard-to-reach group: pregnant women
      with opiate dependency, focussing on their interactions with helping services and
      social networks. The aim was to explore the interactions of pregnant women on
      methadone with helping services and social support, with the objective to make
      recommendations to improve service to this 'hard-to-reach' group. METHOD:
      Questions for staff and client interview schedules were constructed, informed by
      a literature search. Seven methadone clinic staff were interviewed and a
      questionnaire was distributed to 10 antenatal clinic staff known to have
      previously managed pregnant women on methadone. Five methadone clients were
      interviewed at the clinic and interviews taped for transcription with consent.
      FINDINGS: High risk pregnancies warrant a multidisciplinary approach, but in the
      hard-to-reach this ideal can itself be out of reach. Although primary care is
      better placed than secondary care to coordinate maternity and community support
      services, few opiate-dependent people have a regular general practitioner and may
      have perceived or actual barriers to access to care. Perceived stigma deterred
      these women from engaging. Women also fear that services will judge and report
      them, worrying about the health of their child and the powers of child protection
      services. CONCLUSION: A fresh consideration of the functionality of services to
      the hard-to-reach may be beneficial. A nursing concept of 'face-work' throws some
      light on the misperception of well-intentione services by the hard-to-reach.

PMID- 20690405
TI  - Asystole after ear suctioning.

PMID- 20690406
TI  - Nurse and medical (general) practitioners.

PMID- 20690407
TI  - Support for men's health initiatives.

PMID- 20690408
TI  - New Zealand should have mandatory fortification of bread with folic acid: yes.

PMID- 20690409
TI  - Black cohosh (black snakeroot, Cimicifuga racemosa (L.) Nutt., Actaea racemosa
      L.).

PMID- 20690410
TI  - The wahakura and the safe sleeping environment.

PMID- 20690411
TI  - Deceiving third parties.

PMID- 20690412
TI  - Burning mouth syndrome.
AB  - Most clinicians dread seeing the patient presenting with a primary complaint of a
      burning pain on one or more oral mucosal surfaces. Unlike most other clinical
      conditions presenting in a dental office, burning mouth syndrome is recently,
      advances have been made towards clarifying the possible etiology of the disorder
      and testing the possible therapeutic modalities available. This article attempts
      to summarize the "state of the art" today.

PMID- 20690413
TI  - Lymphangiogenesis, lymphatic endothelial cells and lymphatic metastasis in head
      and neck cancer--a review of mechanisms.
AB  - Lymphatic metastasis is a continuous and complicated process. The detailed
      mechanisms of lymphatic metastasis are still not very clear, despite considerable
      research efforts in recent years. Previously, it was commonly accepted that there
      were no lymphatic vessels in the primary tumor. However, recent studies have
      demonstrated that lymphatic vessels are detectable in certain types of cancer,
      and more and more evidence has shown that cancer cells invade into local lymph
      nodes mainly via peritumoral lymphatic vessels. Moreover, activated endothelial
      cells may also be important, having an influence on lymphatic metastasis of
      cancer cells. This article, based on recent research findings, provides an in
      depth discussion of the relationship between lymphangiogenesis, tumor-derived
      lymphatic endothelial cells and lymphatic metastasis in head and neck cancer.

PMID- 20690414
TI  - Effect of Galla chinensis on the in vitro remineralization of advanced enamel
      lesions.
AB  - AIM: The effect of Galla chinensis on de-/re-mineralization of advanced enamel
      lesions was investigated by using micro-CT in a prolonged in vitro experiment.
      METHODOLOGY: Baseline mineral contents of sound enamels were first analyzed. Then
      lesions were produced in an acidic buffer solution (2.2 m mol x L(-1) Ca(NO3)2,
      2.2 mmol x L(-1) KH2PO4, and pH = 4.5) for 21 days, with thrice daily three
      minute treatments, divided into four groups: Group A, 4 000 ppm crude aqueous
      extract of Galla chinensis (GCE); Group B, 4000 ppm gallic acid; Group C, 1000
      ppm F aq. (as NaF, positive control); Group D, deionized water (negative
      control). Next, the blocks were immersed in a remineralization solution (1.5 mmol
      x L(-1) CaCl2, 0.9 mmol x L(-1) KH2PO4, 0.1 ppm F, and pH = 7.0) for 200 days.
      Mineral loss (ML) in each region of interest (ROI) and integrated mineral loss
      (IML) of the lesions were calculated (comparing with baseline mineral content of
      sound enamel) at different time points. RESULTS: After 21 days demineralization,
      fluoride treatment showed a statistically significant demineralization-inhibiting
      effect among the four groups, and after 200 days of remineralization, mineral
      content recovery was ordered (lowest to highest) as A = C < B < D. CONCLUSION:
      GCE could slow down the remineralization of enamel in the surface layer and
      thereby facilitate ion transport into the lesion body. The mechanism of Galla
      chinensis in enhancing the remineralization of dental caries is different from
      fluoride.

PMID- 20690415
TI  - Multilineage differentiation of dental pulp stem cells from green fluorescent
      protein transgenic mice.
AB  - AIM: The aim of this study was to confirm the multilineage differentiation
      ability of dental pulp stem cells (DPSCs) from green fluorescent protein (GFP)
      transgenic mice. The expression of GFP in DPSCs was also observed during
      differentiation. METHODOLOGY: DPSCs were harvested from the dental pulp tissue of
      transgenic nude mice, and then transferred to osteogenic, adipogenic, and
      chondrogenic media. The morphological characterization of induced cells was
      observed by microscopy and histological staining. The expression of marker genes
      was measured by RT-PCR. RESULTS: The endogenous GFP and multilineage potential of
      transgenic DPSCs had no influence on each other. Moreover, the results of
      fluorescence microscopic imaging suggest that there was no significant decline of
      GFP expression during DPSCs differentiation. CONCLUSION: As the population of GFP
      labeled DPSCs can be easily identified, this will be a promising method for
      tracking DPSCs in vivo.

PMID- 20690416
TI  - Effect of self-adhesive resin cement and tribochemical treatment on bond strength
      to zirconia.
AB  - AIM: To evaluate the interactive effects of different self-adhesive resin cements
      and tribochemical treatment on bond strength to zirconia. METHODOLOGY: The
      following self-adhesive resin cements for bonding two zirconia blocks were
      evaluated: Maxcem (MA), Smartcem (SM), Rely X Unicem Aplicap (UN), Breeze (BR),
      Biscem (BI), Set (SE), and Clearfil SA luting (CL). The specimens were grouped
      according to conditioning as follows: Group 1, polishing with 600 grit polishing
      paper; Group 2, silica coating with 110 microm Al2O3 particles which modified
      with silica; and, Group 3, tribochemical treatment--silica coating +
      silanization. Specimens were stored in distilled water at 37 degrees C for 24
      hours before testing shear bond strength. RESULTS: Silica coating and
      tribochemical treatment significantly increased the bond strength of the MA, UN,
      BR, BI, SE and CL to zirconia compared to #600 polishing. For both #600 polished
      and silica coating treatments, MDP-containing self-adhesive resin cement CL had
      the highest bond strengths to zirconia. CONCLUSION: Applying silica coating and
      tribochemical treatment improved the bond strength of self-adhesive resin cement
      to zirconia, especially for CL.

PMID- 20690417
TI  - Nerve growth factor and vascular endothelial growth factor: retrospective
      analysis of 63 patients with salivary adenoid cystic carcinoma.
AB  - AIM: To detect the expression of nerve growth factor (NGF) and vascular
      endothelial growth factor (VEGF) in salivary adenoid cystic carcinoma (SACC)
      tissues, as well as to determine the correlation between growth factor expression
      and prognosis in SACC. METHODOLOGY: Medical records of 63 patients surgically
      treated for SACC between January 1988 and October 2005 were reviewed.
      Immunohistochemistry was performed to examine the expression of NGF and VEGF in
      tumor tissues. Kaplan-Meier analysis and Cox's proportional hazard regression
      model were applied to assess predictors of survival. RESULTS: NGF and VEGF were
      overexpressed in SACC tissues, compared with those in normal salivary tissues (P
      < 0.05), and the staining intensity of these two factors was stronger in groups
      of solid subtype, advanced TNM stage, perineural invasion and recurrence.
      Patients with high-expression of NGF and VEGF, solid subtype, advanced stage,
      perineural invasion, recurrence and extended resection alone had worse survival
      rates (P < 0.05). CONCLUSION: NGF and VEGF are expressed increasingly in the
      tissues of SACC cases with invasion and metastasis. NGF expression and VEGF
      expression are independent

PMID- 20690418
TI  - Cytomorphological analysis of keratinocytes in oral smears from tobacco users and
      oral squamous cell carcinoma lesions--a histochemical approach.
AB  - AIM: To analyse the cytomorphological features of keratinocytes in smears
      obtained from the oral mucosa of tobacco users and from oral squamous cell
      carcinoma lesions. METHODOLOGY: Oral smears were obtained from clinically, normal
      appearing mucosa of oral squamous cell carcinoma patients (n=20) and from the
      mucosa of smokers (n=20), and apparently healthy individuals (n=20) were used as
      controls. The smears were histochemically stained and cytomorphological
      assessment of the keratinocytes was carried out. One-way ANOVA (Analysis of
      Variance) was used for comparing the parameters among multiple groups and Tukey
      HSD test was used to compare the mean values between groups. RESULTS: The mean
      nuclear area of keratinocytes from the mucosa of tobacco users was 46 +/- 2.57
      and that of the oral squamous cell carcinoma lesion was 81.54 +/- 4.31. While
      there was a significant (P = 0.001) reduction in the cellular area of
      keratinocytes from oral squamous cell carcinoma lesion when compared with those
      from oral smears of tobacco users. CONCLUSION: Cytomorphometric analysis of
      keratinocytes can serve as a useful adjunct in the early diagnosis of oral
      squamous cell carcinomas.

PMID- 20690419
TI  - Role of the Chinese herbal medicine xianhuayin on the reversal of premalignant
      mucosal lesions in the golden hamster buccal pouch.
AB  - AIM: To investigate the role of the Chinese herbal medicine Xianhuayin on the
      reversal of 7,12-dimethylbenz[a]anthracene (DMBA)-induced premalignant mucosal
      lesions in the oral buccal pouch of golden hamsters. METHODOLOGY: The animals
      were randomly divided into a non-diseased control group (n=5) and an experimental
      group including 50 animals in which the buccal mucosa had been painted with DMBA
      (0.5% in acetone) to generate an oral mucosa premalignant lesion. Animals in the
      experimental group were further divided into Xianhuayin-treated group (n=30),
      untreated premalignant lesion group (n=10) and normal saline (NS)-treated group
      (n=10). The cheek (buccal) pouch mucosa of the golden hamsters in each group was
      observed with light and electron microscopy eight weeks after intragastric
      administration with NS or Xianhuayin. RESULTS: In the non-diseased control group,
      the buccal mucosa was keratinized and stratified squamous epithelium under a
      light microscope. In the untreated premalignant lesion group, variable degrees of
      epithelial dysplasia was observed. The irregular epithelial mucosa gradually
      became distinct in the Xianhuayin-treated group. Scanning electronic microscopic
      (SEM) analysis showed that surface of the cells exhibited honeycomb structures in
      the hamster of untreated-group. The cells were morphologically irregular,
      overlapped and loosened in the untreated premalignant lesion group. Most of the
      cell surface exhibited honeycomb structure in the Xianhuayin-treated group.
      Transmission electronic microscopic (TEM) analysis showed that buccal mucosal
      epithelial cells were morphologically regular in the non-diseased control group.
      Desmosomes and tonofibrils were reduced and the nucleus was morphologically
      irregular in the untreated premalignant lesion group. In the Xianhuayin-treated
      group, the widening intercellular gap was gradually reduced, desmosomes and the
      cells becoming morphologically regular. No significant difference was observed
      between the hamsters in NS-treated group and those in the untreated premalignant
      lesion group. Significant therapeutic efficacy was observed in the group
      receiving Xianhuayin. CONCLUSION: Xianhuayin is effective in the reversal of DMBA
      induced premalignant lesions in the buccal pouch of golden hamsters.

PMID- 20690420
TI  - The role of host-derived dentinal matrix metalloproteinases in reducing dentin
      bonding of resin adhesives.
AB  - Dentin matrix metalloproteinases (MMPs) are a family of host-derived proteolytic
      enzymes trapped within mineralized dentin matrix, which have the ability to
      hydrolyze the organic matrix of demineralized dentin. After bonding with resins
      to dentin there are usually some exposed collagen fibrils at the bottom of the
      hybrid layer owing to imperfect resin impregnation of the demineralized dentin
      matrix. Exposed collagen fibrils might be affected by MMPs inducing hydrolytic
      degradation, which might result in reduced bond strength. Most MMPs are
      synthesized and released from odontoblasts in the form of proenzymes, requiring
      activation to degrade extracellular matrix components. Unfortunately, they can be
      activated by modem self-etch and etch-and-rinse adhesives. The aim of this review
      is to summarize the current knowledge of the role of dentinal host-derived MMPs
      in dentin matrix degradation. We also discuss various available MMP inhibitors,
      especially chlorhexidine, and suggest that they could provide a potential pathway
      for inhibiting collagen degradation in bonding interfaces thereby increasing
      dentin bonding durability.

PMID- 20690421
TI  - State of the art of Micro-CT applications in dental research.
AB  - This review highlights the recent advances in X-ray microcomputed tomography
      (Micro-CT) applied in dental research. It summarizes Micro-CT applications in
      measurement of enamel thickness, root canal morphology, evaluation of root canal
      preparation, craniofacial skeletal structure, micro finite element modeling,
      dental tissue engineering, mineral density of dental hard tissues and about
      dental implants. Details of studies in each of these areas are highlighted along
      with the advantages of Micro-CT, and finally a summary of the future applications
      of Micro-CT in dental research is given.

PMID- 20690422
TI  - Caries patterns in the primary dentition: cluster analysis of a sample of 5169
      Arizona children 5-59 months of age.
AB  - AIM: Cluster analysis was conducted on data from 5,169 United States (U.S.)
      Arizona children, age's 5-59-months with the goal of delineating patterns of
      caries in the primary dentition of pre-school children without a priori pattern
      definitions. METHODOLOGY: Cluster analyses were conducted using all data for
      children ages 0-4 years in aggregate: (1) for all subjects, and (2) for subjects
      without crowned restored teeth. Each of these two sets of analyses consisted of 8
      differently specified cluster analyses as a validation procedure. RESULTS: The
      caries patterns identified from the clustering analysis are: (1) smooth surfaces
      (other than the maxillary incisor), (2) maxillary incisor, (3) occlusal surfaces
      of first molars, and (4) pit and fissure surfaces of second molars. CONCLUSION:
      The cluster analysis findings were consistent with results produced by
      multidimensional scaling. These cross-validated patterns may represent resulting
      disease conditions from different risks or the timing of various risk factor
      exposures. As such, the patterns may be useful case definitions for caries risk
      factor investigations in children under 60 months of age.

PMID- 20690423
TI  - Relationship of periodontal status and dental caries status with oral health
      knowledge, attitude and behavior among professional students in India.
AB  - AIM: To find the relationship of periodontal status and dental caries status with
      oral health knowledge, attitude, behavior, among professional students in India.
      METHODOLOGY: In a cross sectional study, a total of 825 students (males: 577,
      females: 248) from six professions were surveyed using a self administered
      structured questionnaire including 41 multiple choice questions and the WHO Oral
      Health Assessment Form (1997). The data was analyzed using the SPSS version 13.0
      to perform the Student's t-test, ANOVA test, Scheffe's test and Chi-square test,
      linear regression analysis. RESULTS: The mean percentage scores of the students
      for knowledge were 53.25 +/- 15.05; for attitude 74.97 +/- 20.48; and for
      behavior 59.09 +/- 18.77. The percentage of students with calculus score was
      found to be significantly high (43.8%). The percentage of professional students
      with DMFT >4 was 14.1% and the percentage of students with decayed teeth was
      46.2%. The regression analysis showed that the oral health behavior of the
      students was dependent on the attitude (P < 0.001), but showed no significant
      linear relation with the knowledge. Also, that the mean DMFT score was dependent
      on the oral health behavior (P < 0.05), but showed no significant relationship
      with the knowledge and attitude of the students. The periodontal status was
      independent on the knowledge, but showed a significant relationship with attitude
      and behavior of the students. CONCLUSION: A positive attitude and adherence to
      good oral hygiene behaviors is associated with better oral health.

PMID- 20690424
TI  - Successful treatment of postpeak stage patients with class II division 1
      malocclusion using non-extraction and multiloop edgewise archwire therapy: a
      report on 16 cases.
AB  - AIM: To determine cephalometrically the mechanism of the treatment effects of non
      extraction and multiloop edgewise archwire (MEAW) technique on postpeak Class II
      Division 1 patients. METHODOLOGY: In this retrospective study, 16 postpeak Class
      II Division 1 patients successfully corrected using a non-extraction and MEAW
      technique were cephalometrically evaluated and compared with 16 matched control
      subjects treated using an extraction technique. Using CorelDRAW software,
      standardized digital cephalograms pre- and post-active treatments were traced and
      a reference grid was set up. The superimpositions were based on the cranial base,
      the mandibular and the maxilla regions,and skeletal and dental changes were
      measured. Changes following treatment were evaluated using the paired-sample t
      test. Student's t-test for unpaired samples was used to assess the differences in
      changes between the MEAW and the extraction control groups. RESULTS: The
      correction of the molar relationships comprised 54% skeletal change (mainly the
      advancement of the mandible) and 46% dental change. Correction of the anterior
      teeth relationships comprised 30% skeletal change and 70% dental change.
      CONCLUSION: The MEAW technique can produce the desired vertical and sagittal
      movement of the tooth segment and then effectively stimulate mandibular
      advancement by utilizing the residual growth potential of the condyle.

PMID- 20690425
TI  - The association between lower incisal inclination and morphology of the
      supporting alveolar bone--a cone-beam CT study.
AB  - AIM: To investigate the relationship between the positioning of the lower central
      incisor and physical morphology of the surrounding alveolar bone. METHODOLOGY:
      Thirty-eight patients (18 males, 20 females), with mean age of 13.4 years, were
      included in this study. As part of orthodontic treatment planning the patients
      were required to take dental Cone-beam CT (CBCT) covering the region of lower
      incisors, the surrounding alveolar bone and the mandibular symphysis. The
      cephalometric parameters were designed and measured to indicate the inclination
      of lower central incisor and physical morphology of the adjacent alveolar bone.
      Computer-aided descriptive statistical analysis was performed using SPSS 15.0
      software package for Windows. A correlation analysis and a linear regression
      analysis between the incisor inclination and the alveolar bone morphology were
      performed. RESULTS: Significant positive correlations were found between the
      lower central incisor inclination and the morphological contour of the alveolar
      bone (P < 0.05). The lower central incisor root apex was closer to the lingual
      alveolar crest when it was buccally inclined. CONCLUSION: The morphology of the
      alveolar bone may be affected by incisal inclination.

PMID- 20690426
TI  - Impacted lower third molar fused with a supernumerary tooth--diagnosis and
      treatment planning using cone-beam computed tomography.
AB  - This paper reported a case of fusion between an impacted third molar and a
      supernumerary tooth, in which a surgical intervention was carried out, with the
      objective of removing the dental elements. The panoramic radiography was
      complemented by the Donovan's radiographic technique; but because of the
      proximity of the dental element to the mandibular ramus, it was not possible to
      have a final fusion diagnosis. Hence, the Cone-Beam Computed Tomography-which
      provides precise three-dimensional information-was used to determinate the fusion
      diagnosis and also to help in the surgical planning. In this case report we
      observed that the periapical, occlusal and panoramic were not able to show
      details which could only be examined through the cone-beam computed tomography.

PMID- 20690427
TI  - Extracellular polysaccharides matrix--an often forgotten virulence factor in oral
      biofilm research.

PMID- 20690428
TI  - Tracking in high-frame-rate imaging.
AB  - Speckle tracking has been used for motion estimation in ultrasound imaging.
      Unlike conventional Doppler techniques, which are angle-dependent, speckle
      tracking can be utilized to estimate velocity vectors. However, the accuracy of
      speckle-tracking methods is limited by speckle decorrelation, which is related to
      the displacement between two consecutive images, and, hence, combining high-frame
      rate imaging and speckle tracking could potentially increase the accuracy of
      motion estimation. However, the lack of transmit focusing may also affect the
      tracking results and the high computational requirement may be problematic. This
      study therefore assessed the performance of high-frame-rate speckle tracking and
      compared it with conventional focusing. The effects of the signal-to-noise ratio
      (SNR), bulk motion, and velocity gradients were investigated in both experiments
      and simulations. The results show that high-frame-rate speckle tracking can
      achieve high accuracy if the SNR is sufficiently high. In addition, its
      computational complexity is acceptable because smaller search windows can be used
      due to the displacements between frames generally being smaller during high-frame
      rate imaging. Speckle decor-relation resulting from velocity gradients within a
      sample volume is also not as significant during high-frame-rate imaging.

PMID- 20690429
TI  - Small lesion detection with resolution enhancement compression.
AB  - A novel coded-excitation method, resolution-enhancement compression (REC),
      increases the axial resolution and the echo signal-to-noise ratio (eSNR) for an
      ultrasonic imaging system. The REC technique was examined for its ability to
      improve lesion detectability. The REC technique was used to double the -3-dB
      fractional pulse-echo bandwidth of an ultrasonic source in both simulations and
      experiments. The increase in usable bandwidth increased lesion detectability
      compared to conventional pulsing (CP) techniques and coded excitation using a
      linear chirp (LC). Lesion detectibility was quantified through lesion signal-to
      noise ratio (lSNR), which is a metric that quantifies the ability of an isolated
      observer to detect a focal lesion against a background. In simulations, a higher
      lSNR value was observed using the REC technique for lesions ranging in size from
      1 mm to 8 mm in diameter. In addition, the eSNR was increased by almost 15 dB. To
      validate simulation results, a hydrogel-cone phantom was constructed to provide
      lesions with +6-dB contrast of different sizes. A transducer was scanned
      perpendicular to the major axis of the cone at different levels to provide
      lesions of 3, 5 and 8 mm in diameter. The lSNR was estimated for lesions of
      different sizes and using the three excitation techniques, i.e., CP, LC and REC.
      In experiments, the lSNR was observed to be higher using the REC technique than
      the other pulsing techniques. The lSNR scores for REC were higher by 15%, 45% and
      40% for the 3, 5 and 8 mm over the other two excitation techniques. The eSNR was
      increased by 5.7 dB. Therefore, according to the lSNR metric, the improvement in
      spatial resolution from the REC technique resulted in improved detectability of
      small lesions.

PMID- 20690430
TI  - Optimal transmit phasing for harmonic-background suppression with bipolar square
      wave pulser.
AB  - Optimal transmit phasing has been proposed to increase contrast-to-tissue ratio
      (CTR) by relatively phasing the tissue and leakage harmonic components to cancel
      each other out for tissue-background suppression in harmonic imaging. Since most
      clinical systems are only equipped with a bipolar square-wave pulser, effective
      procedures for binary conversion of continuous transmit signals become essential
      in optimal transmit phasing to generate arbitrarily-phased bipolar waveforms. In
      this study, sigma-delta modulation is combined with code tuning to achieve this
      goal. Measurements of echoes from a wire phantom were performed to investigate
      the difference in harmonic suppression between the original transmit waveform and
      its bipolar counterpart. In-vivo cardiac imaging of a rabbit model was also
      established in the clinical ultrasound system to test the efficacy of a bipolar
      waveform in optimal transmit phasing. Our results indicate that although the
      harmonic magnitude becomes abrupt with the transmit phasing when a bipolar
      waveform is utilized in optimal transmit phasing, effective harmonic suppression
      is still achievable in the tissue background. Based on in-vivo images of seven
      consecutive cardiac cycles, a bipolar transmit waveform with the optimal
      suppression phase generally improves the CTR by 4.9 dB (p < 10(-8)). It should be
      noted, however, that the abrupt harmonic magnitude with transmit phasing could
      pose difficulties in the selection of the optimal suppression phase and thus
      limit the clinical applicability of optimal transmit phasing.

PMID- 20690432
TI  - Physician assistants, economics, and workforce modeling.

PMID- 20690431
TI  - Interlaboratory comparison of backscatter coefficient estimates for tissue
      mimicking phantoms.
AB  - Ultrasonic backscatter is useful for characterizing tissues and several groups
      have reported methods for estimating backscattering properties. Previous
      interlaboratory comparisons have been made to test the ability to accurately
      estimate the backscatter coefficient (BSC) by different laboratories around the
      world. Results of these comparisons showed variability in BSC estimates but were
      acquired only for a relatively narrow frequency range, and, most importantly,
      lacked reference to any independent predictions from scattering theory. The goal
      of this study was to compare Faran-scattering-theory predictions with
      cooperatively-measured backscatter coefficients for low-attenuating and tissue
      like attenuating phantoms containing glass sphere scatterers of different sizes
      for which BSCs can independently be predicted. Ultrasonic backscatter
      measurementswere made for frequencies from 1 to 12 MHz. Backscatter coefficients
      were estimated using two different planar-reflector techniques at two
      laboratories for two groups of phantoms. Excellent agreement was observed between
      BSC estimates from both laboratories. In addition, good agreement with the
      predictions of Faran's theory was obtained, with average fractional (bias) errors
      ranging from 8-14%. This interlaboratory comparison demonstrates the ability to
      accurately estimate parameters derived from the BSC, including an effective
      scatterer size and the acoustic concentration, both of which may prove useful for
      diagnostic applications of ultrasound tissue characterization.

PMID- 20690433
TI  - Dosage adjustments in renal disease and steroid tapers.

PMID- 20690434
TI  - A slight rash develops into a refractory lesion.

PMID- 20690435
TI  - Cancer screening: Guidelines for cervical cytology.

PMID- 20690436
TI  - Helicobacter pylori infection: update on diagnosis and management.

PMID- 20690437
TI  - Are you using checklists? Check!

PMID- 20690438
TI  - Collis-Nissen fundoplication for a symptomatic paraesophageal hernia.

PMID- 20690439
TI  - Hyperphosphatemia: understanding the role of phosphate metabolism.

PMID- 20690440
TI  - Acute pancreatitis.

PMID- 20690441
TI  - Croup.

PMID- 20690442
TI  - Physician assistants in hospital-based specialty practice.

PMID- 20690443
TI  - What is hypertension?

PMID- 20690444
TI  - Patient information. What is hypertension?

PMID- 20690445
TI  - Imaging and biopsy hold the key to knee pain diagnosis.

PMID- 20690446
TI  - GINA: What PAs need to know to protect patients and their families.

PMID- 20690447
TI  - Case of the Month. Barrett's esophagus.

PMID- 20690448
TI  - Number of phlebotomy attempts.

PMID- 20690449
TI  - Blood safety win, lose, or draw lose, or draw. Survey sheds new light on blood
      splash exposures.

PMID- 20690450
TI  - Keeping the U.S. blood supply safe.

PMID- 20690451
TI  - First HIPAA-compliant, online antibody registry in U.S. assists hospitals in
      preventing life-threatening blood-transfusion reactions.

PMID- 20690452
TI  - Histology comes of age.

PMID- 20690453
TI  - Herbal toxicity.

PMID- 20690454
TI  - A LEAN laboratory 'goes green'.

PMID- 20690455
TI  - HIV testing in mental-health settings.

PMID- 20690456
TI  - PAML's scheduling/ inspection solution. Interview by Carren Bersch.

PMID- 20690457
TI  - Pandemic preparation: lessons learned from H1N1.

PMID- 20690458
TI  - Bring on the future of lab medicine.

PMID- 20690459
TI  - Halford delivers Interax paperless package to the lab.

PMID- 20690460
TI  - Impact of culture on commitment, satisfaction, and extra-role behaviors among
      Canadian ER physicians.
AB  - PURPOSE: The purpose of this paper is to explore the impact of hospital emergency
      department culture on the job satisfaction, patient commitment, and extra-role
      performance of Canadian emergency physicians. The conceptual model related four
      cultural archetypes from the competing valued model to the three outcome
      variables. DESIGN/METHODOLOGY/APPROACH: In total, 428 Canadian emergency
      physicians responded to a national survey. The conceptual model was tested via
      structural equation modeling via LISREL 8. FINDINGS: Culture had a relatively
      weak impact on the outcomes. Human resources culture related positively to job
      satisfaction while bureaucratic culture related positively to patient commitment.
      Patient commitment, but not job satisfaction strongly and positively related to
      extra-role behavior. A direct relationship between entrepreneurial culture and
      extra-role behavior emerged from an extended analysis. PRACTICAL IMPLICATIONS:
      Organizational culture seems to have more distal relationships with outcome
      variables and its influence is likely to be mediated by more proximal workplace
      variables. ORIGINALITY/VALUE: Of value by showing that a key modern leadership
      challenge is to create the kind of work culture that can become a source of
      competitive advantage through generating particular organizational outcomes
      valued by stakeholders.

PMID- 20690461
TI  - The enactment of dynamic leadership.
AB  - PURPOSE: The purpose of this paper is to empirically examine how clinical team
      leadership can facilitate a collaborative team and, in doing so, drive change in
      a health service. DESIGN/METHODOLOGY/APPROACH: Ethnographic field work was
      conducted with a clinical team, comprised of 13 health professionals, in
      community health, in Sydney Australia. Utilising semi-structured interviews, data
      were collected and then analysed using Goleman's leadership typology as an
      analytic lens. FINDINGS: Leadership can facilitate a team to realise high levels
      of collaboration, trust and respect. This creates an environment in which
      collective learning and increased responsibility thrives. Together, these
      elements enable front-line staff to take ownership of their services, to
      integrate the organising and delivery of services, and, in doing so, improve
      health care practice. RESEARCH LIMITATIONS/IMPLICATIONS: The leadership
      empirically observed here confirms qualities, behaviours and approaches that have
      been argued as important in the literature. PRACTICAL IMPLICATIONS: For health
      professionals in a clinical team leadership role Goleman's typology can be
      instructive. Many leaders in complex health care organisations are engaged in,
      and needing to respond to, unfolding situations to ensure positive improvement.
      At such times the typology offers a range of leadership styles to draw upon.
      ORIGINALITY/VALUE: The application of the typology to health care clinical team
      leadership is a new development.

PMID- 20690462
TI  - Nursing staff turnover: does leadership matter?
AB  - PURPOSE: The aim of this paper is to study the relation between leadership
      behaviour of nursing managers and staff turnover with respect to the intervening
      variables "work climate" and "job satisfaction". DESIGN/METHODOLOGY/APPROACH:
      Three different well-documented questionnaires were used to assess perceived
      leadership behaviour, work climate and job satisfaction. Data on staff turnover
      were collected from a computerized follow-up system. Different statistical
      analyses such as correlation analyses, regression analyses and analyses of
      variance were performed in order to explore the relations. FINDINGS: The results
      show strong correlations between leadership behaviour, work climate and job
      satisfaction. No significant direct relation between leadership behaviour and
      staff turnover was shown. Staff turnover shows statistically significant
      correlations with the job satisfaction variable "feeling" (p < OR = 0.005), and
      the work climate variables "challenge" and "playfulness" (p < or = 0.001).
      PRACTICAL IMPLICATIONS: In order to limit staff turnover, decision makers should
      put effort into recruiting and retaining managers that perform very well
      according to the needs of staff. Managers that are both relations-oriented and
      production-oriented, can manage change and are able to stimulate the staff with
      challenges have the best opportunities to achieve low staff turnover.
      ORIGINALITY/VALUE: To the best of the authors' knowledge there is no study
      published that explores the influence of leadership behaviour, including the
      dimension "change", on staff turnover in relation to intervening intrinsic
      factors of job satisfaction and creative work climate in nursing.

PMID- 20690463
TI  - Personnel management in Finnish social and health care.
AB  - PURPOSE: The purpose of this study is to examine components of good personnel
      management and how they come true in accounts of social and health care managers.
      DESIGN/METHODOLOGY/APPROACH: The data were obtained by means of a postal survey
      sent to middle-line managers in positions above the first-line management level
      in the responsibility area of Tampere University Hospital. The questionnaire was
      sent to 703 managers; 433 sent in responses indicating a response rate of 62
      percent. FINDINGS: Middle-line managers considered themselves as interactive,
      responsibility-sharing and understanding leaders, but found shortcomings in the
      leadership style of their superiors. Only 18 percent of the middle-line managers
      received feedback and only 42 percent received support from their superiors when
      needed. There were significant differences between genders, activity sectors and
      professional backgrounds in the responders' accounts concerning personnel
      management practices. RESEARCH IMPLICATIONS/LIMITATIONS: The results of this
      study reliably describe how middle-line managers consider things to be, not
      necessarily how things are in reality. PRACTICAL IMPLICATIONS: The findings
      confirm the assumption that the importance of personnel management is still not
      perfectly understood in the upper management levels of the social and health care
      sector. At the same time the self-evaluations of middle-line managers implied an
      ambition towards better personnel management. ORIGINALITY/VALUE: This study
      identifies components of good personnel management from literature and uses them
      as the basis for analysing the data.

PMID- 20690465
TI  - An interview with Brian James, chief executive, Rotherham General Hospital, U.K.
      Interview by Alistair Craven.

PMID- 20690464
TI  - Logistics in hospitals: a case study of some Singapore hospitals.
AB  - PURPOSE: The purpose of this paper is to investigate logistics activities in
      Singapore hospitals. It defines various types of activities handled by a
      logistics division. Inventory management policy and the use of information and
      communication technologies (ICT) for logistics purposes are also discussed. The
      study identifies the nature of strategic alliances in Singapore's health care
      industry. DESIGN/METHODOLOGY/APPROACH: This study was conducted by utilizing a
      framework for data collection, pre-testing the questionnaire and conducting
      interviews. Various relevant literature was reviewed to design the questionnaire.
      FINDINGS: This study finds that logistics division carry out many related
      activities and some of them also provide engineering services. The hospitals make
      use of ICT. The hospitals are clustered under various groups to minimize the cost
      of operation, including the logistics related costs. However, hospitals do not
      see alliances with suppliers as a strategic option; rather they focus on
      outsourcing of logistics services. The findings also show that Singapore
      hospitals have a good stocking policy for both medical and non-medical items so
      that changes in patient mix can be easily handled. ORIGINALITY/VALUE: Singapore
      is continuously improving its health care industry and therefore, the findings
      will help hospitals in other regions to adopt some of the practices, like
      concentrating on local vendors, outsourcing, clustering, and maximum use of
      information technology as competitive factors that can improve the service and
      reduce the cost of operation. The paper suggests motivators and barriers to the
      use of ICT in logistics in the health care industry.

PMID- 20690466
TI  - A practical approach to ethical decision-making.
AB  - PURPOSE: The purpose of this paper is to provide a practical approach to ethical
      decision-making for executives working in the healthcare setting.
      DESIGN/METHODOLOGY/APPROACH: A nine step decision-making algorithm is presented
      to serve as a guide for identifying and resolving complex ethical problems.
      FINDINGS: While decision-making frameworks are not new to the management
      literature, this practical approach outlines a coherent and logical means by
      which executives can articulate a management problem. ORIGINALITY/VALUE:
      Identifies and evaluates potential solutions for consideration, plans an approach
      to implementing the desired solution, and evaluates the impact of their decision.

PMID- 20690467
TI  - Direct-to-consumer-advertising of prescription medicines: a theoretical approach
      to understanding.
AB  - PURPOSE: The pharmaceutical industry is a leader in research and development
      investment. New treatments need to be communicated to the market, and consumers
      are increasingly interested in learning about new drugs. Direct to consumer
      advertising of prescription medicines (DTCA) is a controversial practice where
      many of the arguments for and against are not supported by strong evidence. This
      paper aims to contribute to a research agenda that is forming in this area.
      DESIGN/METHODOLOGY/APPROACH: The paper reports on a systematic review that was
      conducted and applies accepted theoretical models to the DTCA context. The
      systematic review methodology is widely accepted in the medical sector and is
      successfully applied here in the marketing field. FINDINGS: The hierarchy of
      effects model is specifically applied to DTCA with a clear emphasis on consumer
      rights, empowerment, protection and knowledge. ORIGINALITY/VALUE: This paper
      provides healthcare practitioners with insight into how consumers process DTCA
      messages and provides guidance into how to assist in this message processing.

PMID- 20690468
TI  - A systemic approach to developing frontline leaders in healthcare.
AB  - PURPOSE: The purpose of this case study is to extend the understanding of
      leadership development in healthcare by documenting the impact of a systemic
      approach to developing frontline leaders in a large Canadian healthcare
      organization. DESIGN/METHODOLOGY/APPROACH: A total of 92 participants working in
      acute and community settings participated in an eight-day certificate program
      that combined classroom instruction, practical skill development, and applied
      projects. Program content was based on a learning needs assessment conducted with
      potential participants and their supervisors. FINDINGS: Frontline leaders and
      their supervisors rated the program positively in terms of its impact on
      participants' confidence and willingness to lead, awareness of leadership
      opportunities, communication, problem solving, response to conflict, and the
      ability to support their teams through change. It was also found, however, that
      supervisors' ratings were generally lower than those of participants. PRACTICAL
      IMPLICATIONS: Systemic approaches to leadership development offer healthcare the
      best chance of addressing the current leadership crisis. The challenge is finding
      innovative ways to demonstrate sustainable benefits in an industry that is
      struggling to address cost pressures. In the present study, personal and
      supervisor evaluations were used in conjunction with completion of applied change
      projects to demonstrate a tangible return on investment. ORIGINALITY/VALUE:
      Leadership can be learned and there is no better point of entry for development
      than those in frontline leadership positions. However, developing future leaders
      requires the commitment of an entire leadership community. Healthcare
      organizations that are experiencing leadership gaps must be prepared to make a
      long term investment if they want to achieve lasting healthcare reforms.

PMID- 20690469
TI  - Linking learning methods to outcomes in public health leadership development.
AB  - PURPOSE: The purpose of this research is to present evaluation findings from the
      National Public Health Leadership Institute (PHLI) regarding how the curriculum's
      learning methods work singly and together to produce outcomes for learners and
      their organizations. DESIGN/METHODOLOGY/APPROACH: Six months after graduation
      from PHLI, four recent cohorts of PHLI graduates were asked to report overall
      reactions to PHLI by using an online survey. The survey consisted of quantitative
      questions about key leadership behaviors taught in the program and the usefulness
      of PHLI's five learning methods as well as qualitative questions about changes in
      understanding, skill, practices, and outcomes. FINDINGS: The evaluation survey
      yielded a 66 percent response rate (n=133). PHLI's learning methods are
      interrelated and lead to such outcomes as changed leadership understanding,
      knowledge and skill development, increased confidence, increased self-awareness,
      leadership practice changes, and organizational results. The learning project was
      strongly associated with development of collaborations, whereas assessment tools
      and coaching were most often associated with increased self-awareness. RESEARCH
      LIMITATIONS/IMPLICATIONS: These preliminary findings support the idea that
      particular learning methods are related to specific outcomes. However, graduates
      often integrate information and skills from multiple methods to achieve outcomes.
      Future research should investigate whether the associations identified in this
      evaluation are present in other leadership development programs.
      ORIGINALITY/VALUE: This is the first published evaluation that has attempted to
      link specific learning methods with outcomes for participants of a public health
      leadership development program.

PMID- 20690470
TI  - Leaders in hospital-based social work: the roles and functions of directors of
      social work in the case management model.
AB  - PURPOSE: The purpose of this research is to provide an overview of the management
      skills and competencies required by a director of social work as they perform
      their multiple roles and functions in order to effectively manage a medical
      social work team to better serve the needs of patients through the new hospital
      based case management model. DESIGN/METHODOLOGY/APPROACH: This is a conceptual
      paper that reviews the literature on managerial roles, management functions, and
      skills and competencies of directors of social work. Management frameworks that
      are applicable under the case management model are discussed. Interviews with
      five directors of social work and their perceptions are described. FINDINGS:
      Managing a department that is going through continuous changes is often
      difficult. PRACTICAL IMPLICATIONS: This paper has practical implications for
      general health care managers and specifically, directors of social work, to
      develop skills and gain competencies to be successful in today's evolving health
      care environment This research also has practical implications for social workers
      to gain insight into productive and effective ways to collaborate with members of
      an interdisciplinary team. ORIGINALITY/VALUE: This paper is original and of value
      to those working in social work and in the health care field to develop their
      skills and competencies as they perform new roles and functions in the complex
      health care environment.

PMID- 20690471
TI  - Leadership development needs of managers who supervise foreign nurses.
AB  - PURPOSE: This concept paper seeks to outline evidenced-based findings about the
      current experiences, best practices and leadership development needs of nurse
      leaders who work with foreign nurses. DESIGN/METHODOLOGY/APPROACH: A qualitative
      approach was used to collect data for this project. A convenience sample of ten
      nursing leaders from different geographic areas in the USA was telephone
      interviewed to obtain information for this project. PRACTICAL IMPLICATIONS:
      Recommendations are made about the type of educational programming that leaders
      who receive foreign nurses in their work environments will need to facilitate a
      successful transition. ORIGINALITY/VALUE: The legal, ethical and human resource
      issues that surround the international recruitment of nurses have received
      widespread coverage in the media and nursing literature. Although organizations
      which do foreign recruitment invest significant resources, little has been
      written about the challenges in the transition of foreign nurses into healthcare
      practice environments outside their countries of origin. The literature suggests
      that the successful transition of foreign nurses into the healthcare environment
      of another country requires supportive leadership but this does not always occur.

PMID- 20690472
TI  - The adoption of high involvement work practices in Canadian nursing homes.
AB  - PURPOSE: The objective of the research is to assess the degree of adoption of
      high-involvement nursing work practices in long-term care organizations. It seeks
      to determine the organizational and workplace factors that are associated with
      the uptake/adoption of ten selected human resource high-involvement employee work
      practices. DESIGN/METHODOLOGY/APPROACH: A survey questionnaire was sent to 300
      long-term care organizations (nursing homes) in western Canada. Results from 125
      nursing home establishments (43 percent response rate) are reported herein.
      FINDINGS: Of the ten high-involvement nursing work practices examined, employee
      suggestion and recognition systems are the most widely adopted by homes in the
      sample, while shared governance and incentive/merit-base pay are used by a small
      minority of establishments. PRACTICAL IMPLICATIONS: The uptake of high
      involvement nursing work practices is not adopted in a haphazard fashion. Their
      uptake is variously associated with a number of establishment and workplace
      factors, including the presence of a supportive and enabling workplace culture.
      ORIGINALITY/VALUE: The objective of this research is to examine the extent and
      degree of adoption of high involvement work practices in a sample of long-term
      care establishments operating in the four provinces of western Canada.

PMID- 20690473
TI  - Medical talent management: a model for physician deployment.
AB  - PURPOSE: This article aims to provide a focused cost-effective method for
      triaging physicians into appropriate non-clinical roles to benefit both doctors
      and healthcare organizations. DESIGN/METHODOLOGY/APPROACH: Reviews a validated
      career-planning process and customize it for medical talent management. FINDINGS:
      A structured career assessment can differentiate between different physician work
      styles and direct medical talent into best-fit positions. This allows healthcare
      organizations to create a more finely tuned career ladder than the familiar "in
      or out" binary choice. PRACTICAL IMPLICATIONS--Healthcare organizations can
      invest in cost-effective processes for the optimal utilization of their medical
      talent. ORIGINALITY/VALUE: Provides a new use for a well-validated career
      assessment and planning system. The actual value of this approach should be
      studied using best-practices in ROI research.

PMID- 20690474
TI  - Lean as a learning system in a hospital ward.
AB  - PURPOSE: The purpose of this article is to discuss lean as a learning system in a
      hospital ward. DESIGN/METHODOLOGY/APPROACH: Discusses lean as a learning system
      in a hospital ward. FINDINGS: The Toyota veterans are fond of saying, lean is
      about "making people before making parts" or, in the wards' context, developing
      nurses before delivering care. ORIGINALITY/VALUE: This example in using lean to
      carefully build a learning environment for staff and management has implications
      for nursing practice, certainly, but also more generally for lean implementation
      at large.

PMID- 20690475
TI  - Taguchi's experimental design method on improvement of medical image quality.
AB  - PURPOSE: The aim of this article is to show how Taguchi methods can be applied to
      health care to improve the quality of medical images. Quality is often integrated
      with the performance and parameters of the design of medical applications. Many
      imaging methods can be designed by setting the correct combination of parameters
      and estimating the contribution of individual quality influencing factors by
      means of incorporating parameter design and orthogonal arrays. The performance of
      any imaging equipment can be measured by signal-to-noise ratio. This inherent
      index can give a sense of how close the performance is to the ideal.
      DESIGN/METHODOLOGY/APPROACH: Data were collected from a database of 82 diagnostic
      thoracic computed tomography (CT) scans. Signal-to-noise ratios (S/N) were
      calculated. FINDINGS: Given the S/N's, the best CT level was found to be level 4.
      ORIGINALITY/VALUE: To reduce bias resulting from the observer's readings, robust
      equipments should be designed incorporating Taguchi's experimental design.
      Further work is needed to establish imaging protocols and new hardware design.

PMID- 20690476
TI  - The anti-aging revolution.

PMID- 20690477
TI  - Seeds of discord.

PMID- 20690478
TI  - Simple, fresh, tasty and local.

PMID- 20690479
TI  - A primary care-led medical education system?

PMID- 20690480
TI  - Using psychoactive medication to intervene in children's behaviour: an evidence
      based practice?

PMID- 20690481
TI  - Cardiovascular risk assessment and management in mental health clients:
      perceptions of mental health and general practitioners in New Zealand.
AB  - INTRODUCTION: People with mental illness have higher rates of morbidity and
      mortality, largely due to increased rates of cardiovascular disease (CVD).
      Metabolic syndrome is well recognised but rarely expressed as a need to assess
      and manage cardiovascular risk factors; furthermore there is confusion about
      whose role this is. This study explores health practitioners' knowledge,
      attitudes, barriers/solutions towards cardiovascular risk assessment and
      management in mental health patients. METHOD: A survey of mental health
      practitioners (MHPs n = 421) and general practitioners (GPs n = 232) RESULTS:
      Three-quarters of respondents agreed mental illness predisposes to CVD. Fifty
      five percent of MH doctors agreed they could effectively assess CVD risk compared
      to 67% of GPs. Only 21% of MH doctors agreed they could effectively manage CVD
      risk compared to 57% of GPs. Seventy-nine percent of MHPs believed that assessing
      CVD risk was a joint responsibility between GP and MHP, compared to 33% of GPs;
      62% of GPs believed it was their sole responsibility. Forty-six percent of MHPs
      believed managing CVD risk was a joint responsibility compared with 29% of GPs;
      58% of GPs saw this as their role. Only 13% of MHPs and fewer than 4% of GPs
      agreed that MH services were effectively assessing and managing CVD risk. MHPs
      identified lack of knowledge and skills (58%) and poor communication between
      primary-secondary care (53%) as the main barriers. GPs identified barriers of
      poor communication (64%) and patient compliance with health care management
      (71%). The top two solutions proposed by MHPs were provision of GP subsidies
      (47%) and training (43%). GPs also identified provision of a subsidy (66%) and
      collaborative management between GPs and MH (44%) as solutions. CONCLUSION: There
      is widespread recognition of increased risk of CVD in MH patients. MHPs do not
      believe they have the knowledge and skills to manage this risk. GPs believe this
      is their responsibility. Both groups recognise communication with, and access to,
      primary care for MH patients as key barriers.

PMID- 20690482
TI  - Prevalence of acne and its impact on the quality of life in school-aged
      adolescents in Malaysia.
AB  - AIM: The objective of this study was to determine the prevalence of facial acne
      and its impact on the quality of life among adolescents attending secondary
      schools in Muar, Malaysia. METHODS: A cross-sectional study was conducted where
      409 samples were selected using stratified cluster random sampling from two
      secondary schools in Muar, involving Form 1 to Form 5 students. Students were
      diagnosed clinically and the severity of facial acne was assessed using Global
      Acne Grading System. A self-reported Cardiff Acne Disability Index was used to
      assess the quality of life among adolescents who had acne. RESULTS: The
      prevalence of facial acne among the adolescents was 67.5% (n = 276). Facial acne
      increased with increasing age (p = 0.001). It was more common among males (71.1%)
      than females (64.6%), p = 0.165. The males also had a higher prevalence of severe
      acne (p = 0.001). The quality of life was affected by the severity of acne.
      Students with severe acne had higher levels of Cardiff Acne Disability Index (rho
      = 0.521). CONCLUSION: Facial acne is a common disorder and appears to have a
      considerable impact on quality of life among adolescents. The above findings
      should alert health care professionals and the school authorities to actively
      identify, manage and educate adolescents with facial acne.

PMID- 20690483
TI  - The prevalence of depression among Maori patients in Auckland general practice.
AB  - INTRODUCTION: There has been concern over high rates of mental illness in Maori.
      Previous studies in general practice have had small sample sizes. AIM: To
      determine the prevalence of major depression among Maori patients in Auckland
      general practice using the CIDI and the PHQ as measurement tools. METHODS: This
      prevalence study is part of a larger randomised trial. The patients were
      recruited from 77 general practitioners from around Auckland who could provide a
      private room for interviewing. The patients were invited to participate in the
      waiting room and all consecutive patients were approached. For this study all
      patients received a computerised CIDI examination and one third received a PHQ
      assessment prior to getting the CIDI. The interviewer was blind to the
      questionnaire results when the patient did the CIDI. RESULTS: There were 7994
      patients approached from whom there were data on 7432. The prevalence of Maori in
      the study was 9.7%. The overall 12-month prevalence of major depression based on
      the CIDI was 10.1% 95% CI (8.8 to 11.4). For Maori the prevalence was 11.5% 95%
      CI (8.8 to 14.2) and for non-Maori 10.1% 95% CI (8.6 to 11.3). For Maori men and
      Maori women the prevalence was 8.5% and 13.4% and for non-Maori men and non-Maori
      women it was 8.3% and 11.1%. The prevalence of depression over at least the
      previous two weeks on the PHQ > or = 9 for all participants was 12.9% 95% CI
      (11.2 to 14.5). DISCUSSION: The prevalence of depression among Maori is high, but
      not as high as earlier studies. This may be due to the bigger sample size of this
      study.

PMID- 20690484
TI  - Understanding and use of antibiotics amongst Samoan people in New Zealand.
AB  - INTRODUCTION: Use of antibiotics is high in Samoa and this may affect the
      expectations and patterns of antibiotic use of Samoans in New Zealand. AIM: This
      study examined the understanding and reported use of antibiotics amongst Samoans
      in New Zealand. METHODS: In-depth interviews were held with 13 Samoans in New
      Zealand. These interviews were analysed and used to develop a questionnaire that
      was administered to 112 Samoans attending health care facilities in New Zealand.
      RESULTS: Many participants had little understanding of antibiotics. Less than 2%
      identified the correct purpose for antibiotics, and 66% thought they were used to
      relieve pain. Respondents regarded a wide range of medicines (including some
      which they regularly took) as antibiotics. They frequently attributed colds and
      flu to environmental conditions (96%), and regarded antibiotics as a useful
      treatment for them (81%). They reported stopping taking antibiotics before
      finishing the course. Very few (8%) were aware of antibiotic resistance.
      DISCUSSION: Health care practitioners cannot assume that patients share a Western
      scientific understanding of which illnesses are caused by microbes, or what
      antibiotics are or do. People may have significant confusion about the medicines
      they take. Samoans, whether they are born in New Zealand or not, may hold
      traditional Samoan views about health and illness.

PMID- 20690485
TI  - Summary of an evidence-based guideline on soft tissue shoulder injuries and
      related disorders--Part 1: Assessment.
AB  - AIM: To provide a succinct summary of the diagnosis of soft tissue injuries to
      the shoulder for primary health care practitioners based on the New Zealand
      guideline. METHODS: A multidisciplinary team developed the guideline by
      critically appraising and grading retrieved literature using the Graphic
      Appraisal Tool for Epidemiology (GATE). Recommendations were derived from
      resulting evidence tables. RESULTS: Diagnostic ultrasound is a valid tool for the
      diagnosis of a full thickness rotator cuff tear. If a significant tear is
      suspected, referral for diagnostic ultrasound is recommended. There is a paucity
      of evidence for the diagnosis of soft tissue shoulder injuries and most
      recommendations are based on the consensus of the guideline team. CONCLUSION:
      Assessment relies on thorough history-taking and physician examination with
      appropriate referral where there is evidence of serious damage or the diagnosis
      remains unclear.

PMID- 20690486
TI  - Summary of an evidence-based guideline on soft tissue shoulder injuries and
      related disorders--Part 2: Management.
AB  - AIM: To provide a succinct summary of the management of soft tissue injuries to
      the shoulder for primary health care practitioners based on the New Zealand
      guideline. METHODS: A multidisciplinary team developed the guideline by
      critically appraising and grading retrieved literature using the Graphic
      Appraisal Tool for Epidemiology (GATE); and the Scottish Intercollegiate
      Guideline Network. Recommendations were derived from resulting evidence tables.
      RESULTS: For the management of soft tissue shoulder disorders there is little
      evidence to support or refute the efficacy of common interventions for shoulder
      disorders in general and rotator cuff disorders in particular. For rotator cuff
      tendinosis and partial tears, use NSAIDs and subacromial corticosteroid
      injections with caution and provide a trial of supervised exercise. For frozen
      shoulders, intra-articular corticosteroid injection should be considered and
      refer for supervised exercise after acute pain has settled. For shoulder
      instability, good evidence supports the referral of physically active young
      adults for orthopaedic intervention following a first traumatic shoulder
      dislocation. CONCLUSION: While there is a dearth of good evidence, this guideline
      does provide a framework for the management of common soft tissue injuries of the
      shoulder.

PMID- 20690487
TI  - A patient-centred referral pathway for mild to moderate lifestyle and mental
      health problems: does this model work in practice?
AB  - BACKGROUND AND CONTEXT: The Primary Lifestyle Options Programme was an innovative
      eight-month, patient-centred, early primary care-based pilot aimed at identifying
      and promptly enabling people with mild to moderate mental health and lifestyle
      problems to access a range of free interventions as soon as possible. PROBLEMS:
      Mild to moderate mental health and lifestyle issues are easily overlooked in
      primary care. Patients with these problems, once identified, often need support
      to choose and access treatment providers. STRATEGIES FOR IMPROVEMENT: During a GP
      visit a patient requests help by completing a CHAT (Case-finding and Help
      Assessment Tool) which assesses depression, anxiety, abuse, anger, exercise
      level, insomnia, and addictions (gambling, tobacco, alcohol and other
      substances). Patients subsequently have a 30-minute GP consultation where a range
      of services to address identified problem(s) is offered; this choice is assisted
      by a comprehensive resource manual. A programme coordinator facilitates access to
      services by making appointments and liaising between patients and providers. A
      follow-up GP consult is available. RESULTS: 456 patients (6% Maori) aged from 15
      to 84 years requested help via the CHAT for one to seven issues per patient, over
      an eight-month period. Anxiety, depression and insomnia were the commonest
      reasons for requesting help. A feedback questionnaire focussed on the usefulness
      and practicality of the pathway, showing widespread approval from patients, GPs
      and other treatment providers. CONCLUSIONS: This programme enables a patient to
      identify and request help for mental health and lifestyle problems at a mild
      moderate stage, and to be supported through an intervention pathway that
      otherwise is unlikely to be available in a busy primary care environment.

PMID- 20690488
TI  - GPs should prescribe more benzodiazepines for the elderly: yes.

PMID- 20690489
TI  - Bridging two worlds in the interview process --the psychiatric assessment and
      Maori in primary care.

PMID- 20690490
TI  - St John's wort (Hypericum perforatum).

PMID- 20690491
TI  - Destination: recovery Te Unga Ki Uta:Te Oranga. Future responses to mental
      distress and loss of well-being--a discussion paper from the Mental Health
      Advocacy Coalition.

PMID- 20690492
TI  - Effective communication strategies to enhance patient self-care.

PMID- 20690493
TI  - Uncertainty, fear and whistling happy tunes.
AB  - Uncertainty in medical practice is ineradicable, despite great scientific
      advances over the last century. Uncertainty provokes fear, not just in patients
      but also in doctors. Patients cope with theirfear by seeking the advice and
      reassurance of doctors; doctors, on the other hand, cope by denial and self
      deception. But today, in this scientific, truth-seeking age doctors are
      encouraged to share their uncertainty with patients in order to 'empower'
      patients and improve doctor-patient relations. While in theory doctors might
      agree with this approach, in practice they continue to deny it and instead
      whistle happy tunes--deceiving both themselves and their patients. A disclosure
      of uncertainty requires an acknowledgement of uncertainty and, in practice, the
      ability of doctors to acknowledge and to tolerate uncertainty is limited.
      Whenever I feel afraid, I hold my head erect. And whistle a happy tune, So no one
      will suspect I'm afraid. While shivering in my shoes, I strike a careless pose.
      And whistle a happy tune, And no one ever knows. I'm afraid. The result of this
      deception, Is very strange to tell. For when I fool the people I fear, I fool
      myself as well!

PMID- 20690494
TI  - Sub-threshold mental health syndromes: finding an alternative to the medication
      of unhappiness.
AB  - Sub-threshold anxiety and depression are common presentations in primary care.
      They carry a significant disability burden along with the risk of developing a
      frank disorder. Intervention options are limited, although there is some evidence
      that ultra brief interventions may be effective with this patient group. We argue
      that there is a need for a systematic but ultra brief, minimal contact
      intervention, that can be delivered by GPs or practice nurses. Such an
      intervention would be a form of facilitated self-management, a step up from self
      help, from which people could be referred on to more intensive treatment or
      medication if required.

PMID- 20690495
TI  - Mind over matter--implications for general practice.

PMID- 20690496
TI  - Intravenous vitamin C.

PMID- 20690497
TI  - Commensal oral Candida in Asian cohorts.
AB  - The oral carriage rate of Candida in healthy humans ranges from 40% to 60%.
      However for a prolonged period, the oral candidal prevalence in humans was
      documented essentially using data from studies in the West as their prevalence in
      inhabitants in different regions of the world, including Asia was not known. Yet,
      recent reports from a number of studies indicate the quality, quantity and
      prevalence of oral yeasts differ between Asia and other regions for reason that
      are still unclear. This mini review on such data from Asian studies on oral
      carriage of Candida provides another intriguing facet of the behavior of this
      ubiquitous yeast.

PMID- 20690498
TI  - Mesenchymal stem cells and tooth engineering.
AB  - Tooth loss compromises human oral health. Although several prosthetic methods,
      such as artificial denture and dental implants, are clinical therapies to tooth
      loss problems, they are thought to have safety and usage time issues. Recently,
      tooth tissue engineering has attracted more and more attention. Stem cell based
      tissue engineering is thought to be a promising way to replace the missing tooth.
      Mesenchymal stem cells (MSCs) are multipotent stem cells which can differentiate
      into a variety of cell types. The potential MSCs for tooth regeneration mainly
      include stem cells from human exfoliated deciduous teeth (SHEDs), adult dental
      pulp stem cells (DPSCs), stem cells from the apical part of the papilla (SCAPs),
      stem cells from the dental follicle (DFSCs), periodontal ligament stem cells
      (PDLSCs) and bone marrow derived mesenchymal stem cells (BMSCs). This review
      outlines the recent progress in the mesenchymal stem cells used in tooth
      regeneration.

PMID- 20690499
TI  - Introduction of Japanese Society of Oral Implantology.

PMID- 20690500
TI  - Effect of same-dose single or dual field irradiation on damage to miniature pig
      parotid glands.
AB  - AIM: To evaluate the effect of single or dual field irradiation (IR) with the
      same dose on damage to miniature pig parotid glands. METHODOLOGY: Sixteen
      miniature pigs were divided into two IR groups (n=6) and a control group (n=4).
      The irradiation groups were subjected to 20 Gy X-radiation to one parotid gland
      using single-field or dual-field modality by linear accelerator. The dose-volume
      distributions between two IR groups were compared. Saliva from parotid glands and
      blood were collected at 0, 4, 8 and 16 weeks after irradiation. Parotid glands
      were removed at 16 weeks to evaluate tissue morphology. RESULTS: The irradiation
      dose volume distributions were significantly different between single and dual
      field irradiation groups (t=4.177, P=0.002), although dose volume histogramin
      (DVH) indicated the equal maximal dose in parotid glands. Saliva flow rates from
      IR side decreased dramatically at all time points in IR groups, especially in
      dual field irradiation group. The radiation caused changes of white blood cell
      count in blood, lactate dehydrogenase and amylase in serum, calcium, potassium
      and amylase in saliva. Morphologically, more severe radiation damage was found in
      irradiated parotid glands from dual field irradiation group than that from single
      field irradiation group. CONCLUSION: Data from this large animal model
      demonstrated that the radiation damage from the dual field irradiation was more
      severe than that of the single field irradiation at the same dose, suggesting
      that dose-volume distribution is an important factor in evaluation of the
      radiobiology of parotid glands.

PMID- 20690501
TI  - Changes of the unique odontogenic properties of rat apical bud cells under the
      developing apical complex microenvironment.
AB  - AIM: To characterize the odontogenic capability of apical bud and phenotypical
      change of apical bud cells (ABCs) in different microenvironment. METHODOLOGY:
      Incisor apical bud tissues from neonatal SD rat were dissected and transplanted
      into the renal capsules to determine their odontogenic capability. Meanwhile ABCs
      were cultured and purified by repeated differential trypsinization. Then ABCs
      were cultured with conditioned medium from developing apical complex cells (DAC
      CM). Immunocytochemistry, reverse transcriptase polymerase chain reaction (RT
      PCR) and scanning electron microscope (SEM) were performed to compare the
      biological change ofABC treated with or without DAC-CM. RESULTS: First we
      confirmed the ability of apical bud to form crown-like structure ectopically.
      Equally important, by using the developing apical complex (DAC) conditioned
      medium, we found the microenvironment created by root could abrogate the "crown"
      features of ABCs and promote their proliferation and differentiation. CONCLUSION:
      ABCs possess odontogenic capability to form crown-like tissues and this property
      can be affected by root-produced microenvironment.

PMID- 20690502
TI  - Identification of known and novel PTCH mutations in both syndromic and non
      syndromic keratocystic odontogenic tumors.
AB  - AIM: To clarify the role of PTCH in patients with NBCCS-related and non-sydromic
      keratocystic odontogenic tumors. METHODOLOGY: Mutation analysis was undertaken in
      8 sporadic and 4 NBCCS-associated KCOTs. RESULTS: Four novel and two known
      mutations were identified in 2 sporadic and 3 syndromic cases, two of which being
      germline mutations (c.2179delT, c.2824delC) and 4 somatic mutations (c.3162dupG,
      c.1362-1374dup, c.1012 C>T, c.403C>T). CONCLUSION: Our findings suggest that
      defects of PTCH are associated with the pathogenesis of syndromic as well as a
      subset of non-syndromic KCOTs.

PMID- 20690503
TI  - Sequential fluorescent labeling observation of maxillary sinus augmentation by a
      tissue-engineered bone complex in canine model.
AB  - AIM: To evaluate the effects of maxillary sinus floor elevation by a tissue
      engineered bone complex of beta-tricalcium phosphate (beta-TCP) and autologous
      osteoblasts in dogs. METHODOLOGY: Autologous osteoblasts from adult Beagle dogs
      were cultured in vitro. They were further combined with beta-TCP to construct the
      tissue-engineered bone complex. 12 cases of maxillary sinus floor elevation
      surgery were made bilaterally in 6 animals and randomly repaired with the
      following 3 groups of materials: Group A (osteoblasts/beta-TCP); Group B (beta
      TCP); Group C (autogenous bone) (n=4 per group). A polychrome sequential
      fluorescent labeling was performed post-operatively and the animals were
      sacrificed 24 weeks after operation for histological observation. RESULTS: Our
      results showed that autologous osteoblasts were successfully expanded and the
      osteoblastic phenol-types were confirmed by ALP and Alizarin red staining. The
      cells could attach and proliferate well on the surface of the beta-TCP scaffold.
      The fluorescent and histological observation showed that the tissue-engineered
      bone complex had an earlier mineralization and more bone formation inside the
      scaffold than beta-TCP along or even autologous bone. It had also maximally
      maintained the elevated sinus height than both control groups. CONCLUSION: Porous
      beta-TCP has served as a good scaffold for autologous osteoblasts seeding. The
      tissue-engineered bone complex with beta-TCP and autologous osteoblasts might be
      a better alternative to autologous bone for the clinical edentulous maxillary
      sinus augmentation.

PMID- 20690504
TI  - Treatment of varicose veins with minimally invasive methods: is conventional
      surgery still a "gold standard"?
AB  - AIM: To assess the current role of thermal ablation in the treatment of saphenous
      reflux in comparison to more conventional methods. METHOD: Some pertinent
      publications are presented as well as the author's experience with thermal
      ablation using ClosureFast. RESULTS: Over the last decade several techniques for
      thermal ablation of saphenous reflux have been developed. There is some evidence-
      although scarce--that thermal ablation was from the start not inferior to
      standard surgery (high ligation and stripping). In addition, more recent thermal
      ablation techniques appear to have milder side effects than the pioneers.
      CONCLUSION: Thermal ablation of saphenous reflux has quickly assumed an important
      role in the treatment of varicose veins and the parameters of thermal ablation
      may further be optimised. Therefore, we believe that high ligation and stripping
      of refluxing saphenous veins will widely be displaced by thermal ablation.

PMID- 20690505
TI  - Feasibility of percutaneous radiofrequency ablation for pulmonary malignancies in
      the hands of the surgeon.
AB  - AIM: To assess the feasibility of percutaneous pulmonary radiofrequency ablation
      (RFA) executed by a single surgeon. MATERIALS AND METHODS: Between 2007 and 2010,
      15 procedures were performed in 11 patients during 13 sessions. Sex, age,
      pulmonary localisation and tumor diameter are discussed. Metastatic lesions as
      well as pulmonary primitive malignancies were treated. For metastatic lesions,
      the primitive tumor was considered as completely treated. Surgery was refused
      because of impaired pulmonary function or due to patient's refusal. All
      interventions were carried out by a single thoracic surgeon under CT-guidance in
      the department of radiology. RESULTS: RFA was completed in all patients without
      perprocedural complications. There was no significant perioperative morbidity.
      Pneumothorax was the most frequent complication but none of the patients needed
      thoracic drainage. Hospital stay decreased progressively since the start of this
      series. Follow-up was complete. Most lesions were stable or diminishing in size.
      CONCLUSION: These early results show that pulmonary RFA is a safe and feasible
      technique in the hands of the surgeon. Longer follow-up and larger series will be
      welcome to confirm the results and position of this procedure which might become
      an important tool for the surgeon and not only for radiologists.

PMID- 20690506
TI  - Emergency endovascular aneurysm repair for ruptured abdominal aortic aneurysms:
      an institutional experience.
AB  - OBJECTIVES: Emergency endovascular aneurysm repair (eEVAR) for ruptured abdominal
      aortic aneurysms (rAAA) is still under investigation. Since installation of an
      urgent eEVAR kit in our hospital, all patients with a rAAA or urgent thoracic
      aortic aneurysm are candidates for eEVAR or eTEVAR (emergency thoracic EVAR),
      respectively. For this study, we analyzed all rAAA patients treated with eEVAR.
      METHODS: Data were recorded prospectively. Criteria for an eEVAR were an
      infrarenal neck > or = 15 mm, acceptable landing zone, angles below 70 degrees
      and a good femoral approach. We prefer preoperative angio CT-scan but in case of
      instability, an intra-aortic balloon can stabilize the patient during angiography
      (in the OR) to decide between open or eEVAR repair. Follow-up was performed on
      regular intervals by duplex or CT-scan. Thirty-day mortality and overall survival
      were calculated. RESULTS: Since 2006, nine male rAAA patients with a mean age of
      73 years (range : 62-82) had eEVAR repair. Aneurysm diameter was 8 cm (range :
      5.8-11). The Hardman index was 1.5 (range : 0-3). In eight patients an aorto-uni
      iliac device was placed succesfully followed by a femorofemoral crossover bypass.
      The 30-day operative mortality was 12.5% (one patient with septic shock). Three
      patients showed a type 2 endoleak with stable diameter during follow-up but one
      patient showed expansion 4 years after treatment. CONCLUSIONS: Treating rAAA with
      eEVAR in selected patients with acceptable anatomy and a kit permanently
      available in the operating room yielded good results by a surgical team trained
      for both open and eEVAR repair. The conversion rate was low (11%) and the
      survival (immediate and 30-days) was excellent (87.5%).

PMID- 20690507
TI  - Is there a proper way to treat shortened oesophagus? About a series of 67
      patients.
AB  - INTRODUCTION AND OBJECTIVE: During the work-up of gastro-oesophageal reflux
      disease (GORD) patients, barium swallow may show a shortened oesophagus with a
      non-reducible gastro-oesophageal junction. In our department, in such cases, a
      Collis-Nissen operation is usually planned. But, the proper reducibility of the
      gastro-oesophageal junction (GOJ) in the abdomen is difficult to assess
      peroperatively. The aim of this study is to compare retrospectively the follow-up
      of an oesophageal lengthening procedure (Collis-Nissen gastroplasty) versus a
      standard Nissen in the management of patients with primary short oesophagus or
      secondary to previous Nissen fundoplication. PATIENTS AND METHODS: Between
      01/2000 and 12/2009, 67 patients with a short oesophagus on X-Ray were operated
      on for proven GORD: 27 (Group A) underwent a Collis-Nissen fundoplication. In 40
      patients (Group B), the GOJ was reduced easily and a standard Nissen
      fundoplication was judged sufficient by the experimented surgeon. Follow up
      included Quality of Life evaluation using the Gastrointestinal Quality of Life
      Index (GIQLI) and a barium swallow. RESULTS: 64 patients agreed to participate.
      Mean follow up was 46 months (4-122). Mean postoperative GIQLI score was 108 in
      group A, 97 in group B. Barium swallow was performed in 61 patients. In group A,
      seven patients out of 25 (28%) presented a intrathoracic migration on X-Ray while
      in group B, it was noted in 20 patients (55%). CONCLUSION: According literature,
      Collis gastroplasty allows a tension-free fundoplication to be performed to
      correct a shortened oesophagus. Though our series of brachy-oesophagus is small,
      it confirms a better outcome after a Collis-Nissen gastroplasty, compared to the
      classical Nissen fundoplication.

PMID- 20690508
TI  - Belgian and European experience with the European Homograft Bank (EHB)
      cryopreserved allograft valves.--assessment of a 20 year activity.
AB  - European Homograft Bank (EHB) has been selecting, preparing, storing and
      distributing the cryopreserved allograft valves in Belgium and some other
      European Countries since 1989. It was established in 1988 by a pathologist and
      the cardiac and vascular surgeons from Belgian and other European centres as an
      inter-university, international nonprofit association. Due to its neutral
      behavior and very high quality criteria, European Homograft Bank became one of
      the prominent heart valve banks in Europe and wider. It collaborates with the
      transplant coordination in donor selection as well as with the huge network of
      the implanting surgeons in Belgium and other European Countries. The EHB
      responsible discusses with the implanting surgeon the allograft selection on
      basis of the indication and the patients state of emergency. A total of 8.911
      donor heart valves have been evaluated in EHB during the last 20 years. After
      selection, 5.258 allograft valves (1.996 aortic, 3.189 pulmonary and 73 mitral)
      were cryopreserved and stored in vapors of liquid nitrogen between 6 weeks and 5
      years. A total of 4.516 allograft valves (1.391 aortic, 2.620 pulmonary and 48
      mitral) were implanted in the left or right ventricular outflow tract for
      replacement of the diseased aortic or pulmonary valve and for mitral or tricuspid
      valve replacement or repair. In 1.380 cases the allograft valves were used for
      right ventricular outflow tract reconstruction as part of the Ross- procedure,
      whereas in 668 cases the allograft valve served for replacement of the aortic
      valve for endocarditis. The most important indications for use of cryopreserved
      allograft valves were: important cardiac and valve malformation in children,
      female patients of child-bearing age with diseased cardiac valves, cases with
      contra-indication for anti-coagulation and the patients with severe endocarditis
      with septal or annular abscesses. Although the number of the donation increased
      by year, the available allograft valves in stock are still insufficient to
      respond to all the surgeons' request for different indications.

PMID- 20690509
TI  - Endolaser vein surgery with the 1470 nm laser: a report on 120 cases.
AB  - From October 2007 till March 2008, 120 patients were treated by 1470 nm Endolaser
      Vein Surgery. A study was performed with regard to patient population, treatment,
      results and outcome.

PMID- 20690510
TI  - Laparoscopic management of gastrointestinal stromal tumours.
AB  - Gastrointestinal stromal tumours (GISTs) represent the most common non-epithelial
      tumour of the digestive tract. Laparoscopic approach may be considered ideal for
      the resection of these tumours. Their particular biological behaviour allows for
      a curative resection even without large resection margins and extensive
      lymphadenectomies. METHOD: Over a period of five years, eight patients benefited
      from laparoscopic resections (six patients with primary gastric GIST and two
      patients with small bowel GIST). Pathological features were analyzed including
      tumour size, surgical margin status, immunohistochemical staining profile, and
      tumour mitotic index. All cases were confirmed GISTs by immunohistochemical
      staining. RESULTS: The mean age of the patients was 61.6 years (range 48-71
      years). Of these patients, five initially presented to hospital with acute
      gastrointestinal haemorrhage (four cases) or occult bleeding (one case). Gastric
      or small bowel tumours were identified during subsequent investigation. A
      presumptive diagnosis of gastric GIST was made in gastric lesions based on
      endoscopic, ultrasonic, and CT scan characteristics. Small bowel tumours were
      identified and presumed to be GIST based on information gathered from video
      capsule endoscopy, enteroscopy and CT scan. Complete resection was obtained with
      laparoscopic approach in six cases, while in two cases resection was
      laparoscopically assisted, with added oncology safety margins as preoperative
      definitive diagnosis was not available. Tumours varied in dimension from 2.5 cm
      to 9 cm and their malignant risk score using Fletcher criteria was low in three
      cases, intermediate in three cases and high in two cases. Mean postoperative stay
      was 3.8 days and there were no complications, nor postoperative mortality. After
      a mean follow-up of 26 months (range 1 to 60 months) all patients are symptom
      free and free of recurrent disease. CONCLUSIONS: A selective approach to
      laparoscopic resection of gastro-intestinal GISTs allows safe resection and very
      good results, on the condition that a clear diagnosis of GIST has been
      established on preoperative assessment. The laparoscopic feasible and safe
      considering the biological particularities of GIST, and it carries no additional
      risks.

PMID- 20690511
TI  - Scar endometriosis in the abdominal wall: a predictable condition for experienced
      surgeons.
AB  - PURPOSE: Endometriosis in surgical scars develops in 0.1% of those women who
      undergo Caesarean section or other obstetric surgery. Herein we analyse and
      discuss the clinico-pathological characteristics of 15 patients with scar
      endometriosis in the abdominal wall. METHODS: Fifteen cases of scar endometriosis
      in the abdominal wall that were treated surgically in our department between 2003
      and 2009 were examined retrospectively. Age, parity, complaint, medical or
      surgical history, pre/postoperative hormonotherapy, size of the mass, surgical
      procedure, follow-up and disease recurrence were analysed. RESULTS: This
      retrospective study included 15 patients presenting with 17 postoperative
      abdominal wall masses. The mean age of the patients was 32.1 +/- 6.0 years
      (range, 23-48). Eleven of the patients had a painful mass that became bigger
      before menstruation, two had palpable masses only, and two were hospitalised
      because of a mass with persistent pain. The locations of the masses were as
      follows: eight were close to the right side and three were close to the left
      side; two were in the middle of the Pfanenstiel incision and two were in trocar
      tracts. The patients' surgical histories included Caesarean section in thirteen,
      bilateral laparoscopic ovarian cyst excision in one, and laparoscopic
      appendectomy in one. CONCLUSIONS: If a patient presents with incision pain and a
      palpable mass after gynaecologic surgery, an incisional endometrioma should be
      considered. Surgical excision and hormone therapy are effective treatment
      approaches in these patients.

PMID- 20690512
TI  - Influence of surgical complications on the level of pain after radical
      inguinal/iliacal lymph node dissection.
AB  - BACKGROUND: We collected the data of 288 patients with malignant skin tumours. We
      analysed the postoperative pain assessed by a visual analogue scale (VAS) to
      evaluate the quality of our standard peri-operative pain therapy after a radical
      inguinal and iliacal lymph node dissection (RILND) as well as the influence of
      postoperative surgical complications on the level of pain. MATERIALS AND METHOD:
      The postoperative level of pain of 85 patients with malignant skin tumours who
      underwent a RILND between August 2003 and December 2007 was recorded
      prospectively. Patients received a standardised perioperative pain therapy
      according to level I or II of the World Health Organisation (WHO) ladder of pain.
      The efficiency of our pain therapy was registered via VAS in the morning of the
      first three postoperative days. RESULTS: Using our standard pain therapy, we
      determined a VAS < 30 in rest during the first three postoperative days, but
      significantly more pain (VAS median 50-30) (p < 0.001) under stress. Patients
      with surgical complications in the postoperative period (n = 71) had
      significantly more pain in the postoperative period compared to patients with a
      regular postoperative course (p = 0.047). CONCLUSIONS: Immediately after a RILND,
      an analgesic therapy according to level I or II of the WHO pain ladder does not
      seem to be effective enough. Postoperative surgical complications lead to a
      higher VAS level of pain in the postoperative period.

PMID- 20690513
TI  - A comparison of the peri-operative data after open radical retropubic
      prostatectomy or robotic-assisted laparoscopic prostatectomy.
AB  - PURPOSES: To compare the peri-operative biochemical data, the postoperative need
      for help with hygiene and mobility, and the duration of bladder catheterization,
      hospitalization and ICU stay of patients undergoing radical retropubic
      prostatectomy (RRP) versus robotic-assisted laparoscopic prostatectomy (RALP)
      performed by an experienced open, yet inexperienced laparoscopic, surgical team,
      in a peripheral low-volume urological centre. METHODS: Over a 4-year period (2004
      2008), 22 men underwent radical prostatectomy without lymphadenectomy at the
      study institution. The mean age of the patients was 63.9 years and the mean PSA
      value at the time of diagnosis was 9.2 ng/mL. RESULTS: Patients in the robotic
      assisted laparoscopic prostatectomy group presented a significantly lower
      decrease in haemoglobin, haematocrit and total plasmatic protein and a
      significantly smaller need for help with hygiene and mobility and a shorter
      duration of bladder catheterization, hospitalization and ICU stay. CONCLUSIONS:
      The results of this study have shown that robotic-assisted laparoscopic
      prostatectomy is associated with lower peri-operative morbidity and a shorter
      hospital stay than radical retropubic prostatectomy, even when only considering
      the first performed robotic-assisted laparoscopic prostatectomies by a yet
      inexperienced robotic team in a peripheral low-volume urological centre.

PMID- 20690514
TI  - Motor coordination assessment in practicing surgeons and medical students.
AB  - INTRODUCTION: Manual and motor coordination skills are commonly believed to be
      necessary for the surgical profession. AIM OF STUDY: To assess motor coordination
      skills in medical students, surgical residents and attending surgeons. MATERIAL
      AND METHODS: The study group consisted of 17 surgeons and 44 medical students.
      All participants were tested with a number of tests for motor coordination.
      Statistical analysis with ANOVA/MANOVA methods, contrast analysis and post-hoc
      test as appropriate. RESULTS: There were no gender related differences in
      coordination skills. The group of students had significantly lower results in
      comparison to surgeons. Statistical significance (p < 0.05) was observed in
      perception diversity test, and Perception-Diversity-Orientation Index. There was
      no statistically significant difference between residents and attending surgeons
      CONCLUSION: Our results demonstrated that coordination skills are not related to
      gender. They may serve as one of the selection criteria to surgical profession.
      The level of coordination skills is helpful in designing of individual training
      program.

PMID- 20690515
TI  - Late recovery of atrioventricular conduction after pacemaker implantation for
      complete heart block in congenital heart disease: fact or fluke?
AB  - OBJECTIVES: Pacemaker implantation is a standard recommendation for patients with
      persistent complete heart block with congenital heart disease. This study was
      performed to determine the incidence and clinical significance of late recovery
      of atrioventricular (AV) conduction following pacemaker implantation. METHODS: A
      retrospective study of patients with congenital heart disease needing pacemaker
      implantation was performed between 1977 and 2008 at our institution. The
      postoperative course of all patients with complete heart block, in whom a
      permanent pacemaker was implanted, was followed on a semi-annual basis by
      clinical follow-up. RESULTS: A total of 56 patients with complete heart block
      underwent pacemaker implantation. Indications for pacemaker implantation could be
      categorized in primary AV conduction block (n = 28 ; 50%) and surgically-induced
      AV conduction block (n = 28 ; 50%). After pacemaker insertion, recovery of AV
      conduction was recognized in two patients. The first patient was operated for
      atrial septal defect type ostium secundum with complete heart block
      preoperatively. AV block resolved 2 days after pacemaker implantation. The second
      patient underwent mitral valve replacement. Postoperatively, the patient
      developed second degree heart block, which progressed 3 years later into complete
      heart block. A recovery of AV conduction was seen 7.5 years later. In these
      patients, no late recurrence of complete heart block was found during follow-up
      after 8 and 4 months, respectively. CONCLUSIONS: Recovery of AV conduction was
      observed in one patient with primary AV conduction block and in one patient with
      complete heart block after congenital heart surgery. Lifelong cardiac pacing in
      these specific subsets of patients may not be necessary.

PMID- 20690516
TI  - Splenic artery aneurysm in a cardiac transplant patient: a case report.
AB  - We present the case of a 61-year-old woman who underwent repair of a symptomatic
      4-cm splenic artery aneurysm. This patient had received heart transplantation for
      hypertrophic congestive cardiomyopathy 5 years before this event. She was under
      immunosuppression therapy with cyclosporine, prednisone and azathioprine. The
      aneurysm was ligated both proximally and distally without removal of the spleen.
      To our knowledge, this is the first reported case of an isolated splenic artery
      aneurysm in the heart transplant population. We discuss the potential role of
      immunosuppressive agents and hormonal factors in the development of this
      extremely rare occurrence.

PMID- 20690517
TI  - Aneurysm of the splenic artery which arises from the superior mesenteric artery:
      a case report.
AB  - Aneurysm of the splenic artery which arises from the superior mesenteric artery
      is a very rare condition with less than twenty cases described in the literature.
      Most of the time, it is asymptomatic and the diagnosis is fortuitous, but the
      patient can feel epigastric or left upper quadrant discomfort. One can palpate an
      abdominal mass or hear an abdominal systolic murmur. The most fatal presentation
      is the life-threatening rupture. We report the case of a 41-year-old woman
      presenting an aneurysm of the splenic artery originating from the superior
      mesenteric artery treated surgically by simple aneurismal resection with neither
      arterial reconstruction nor splenectomy. The different treatment modalities are
      discussed, taking into account the presence of the vascular malformation.

PMID- 20690518
TI  - Acute appendicitis after liver transplantation: a case report and review of the
      literature.
AB  - INTRODUCTION: Acute appendicitis is rarely seen after liver transplantation.
      CASE: We present a case of acute appendicitis 16 days after liver
      transplantation. CT-scan suggested this diagnosis, but there were also signs of
      biliary leakage. Surgical exploration only revealed an acute appendicitis and an
      appendectomy was performed. Histological examination confirmed the diagnosis.
      Postoperative course was uneventful. LITERATURE: Until now only 15 cases of acute
      appendicitis after liver transplantation have been reported. CT-scan is
      considered to be an accurate diagnostic tool. The duration of hospitalization
      after appendectomy seems to be longer in the immunosuppressed patient.
      CONCLUSION: Although acute appendicitis is not common after liver
      transplantation, quick diagnosis and treatment can prevent major complications.

PMID- 20690519
TI  - Severe stomatitis complicating immune-suppressive switch after cardiac
      transplantation.
AB  - Everolimus is a recently developed immunosuppressive drug for patients following
      solid organ transplantation. Its mechanism of action, independent of calcineurin,
      is different from that of ciclosporin and tacrolimus and because of its lack of
      nephrotoxicity, it is a good alternative for calcineurin inhibitors in patients
      with renal dysfunction. In this paper we describe the case report of a 66-year
      old caucasian female who underwent heart transplantation in December 2006. After
      induction with rabbit anti-thymocytic globulin, her immunosuppressive therapy
      comprised the combination of tacrolimus, mycophenolate mofetil (MMF) and
      steroids. Because of renal dysfunction, tacrolimus was changed for everolimus
      after 6 months. Unfortunately our patient developed severe stomatitis with
      aphthous ulcerations, shortly after the switch. Despite oral therapy (local
      anaesthetics), severe pain and malnourishment prompted interruption of everolimus
      and MMF and therapy was changed to ciclosporin and azathioprine. In addition,
      thalidomide was added. During the following weeks, there was progressive healing
      of the ulcerations. MMF was re-introduced and thalidomide was stopped after 6
      weeks, without recurrent lesions after 4 months of follow-up.

PMID- 20690520
TI  - Stent-grafting of a dissected aortic arch and descending aorta after debranching
      of the supra-aortic vessels: case-presentation, indications, technique.
AB  - Endovascular repair of thoracic aorta pathology is emerging as the preferred
      treatment strategy in high risk patients. Hybrid techniques with debranching of
      the supra-aortic vessels extend indications for endovascular repair of the aortic
      arch and descending aorta. After a brief case-presentation, we describe these
      procedures, outline the indications and discuss the outcomes and results
      available in present literature.

PMID- 20690521
TI  - Hybrid treatment of aberrant right subclavian artery and its aneurysms.
AB  - PURPOSE: To describe two cases of aberrant right subclavian artery (ARSA)
      aneurysm treated with hybrid repair. CASE REPORTS: 77 year old woman with a
      symptomatic ARSA aneurysm was treated with endoluminal aortic stent graft
      exclusion and placement of a plug distal to the aneurysm. Ischemia of the right
      arm required immediate carotid-subclavian bypass. Postoperatively, mild signs of
      brain stem infarction were present with absent flow in the right vertebral
      artery. Because of preserved left vertebral and basilary artery flow no invasive
      therapy was undertaken. The patient recovered completely. A 51 year old woman
      with a symptomatic 37 mm diameter ARSA aneurysm underwent bilateral carotid
      subclavian bypasses and subsequent endoluminal aortic stent graft exclusion of
      the ARSA's origin. Recovery was uneventful. CONCLUSION: Hybrid techniques are
      less invasive valuable alternatives in the treatment of ARSA and its aneurysms.
      Great care should be taken to preserve the posterior cerebral and upper extremity
      circulation.

PMID- 20690522
TI  - Nephrotic syndrome as first manifestation of a bronchopulmonary malignancy. A
      case report.
AB  - We present two cases of a bronchopulmonary tumor with paraneoplastic nephrotic
      syndrome as initial manifestation. After surgical resection of the tumor,
      regression of the nephrotic syndrome occurred.

PMID- 20690523
TI  - Encapsulating peritoneal sclerosis in a peritoneal dialysis patient with prune
      belly syndrome: a case report.
AB  - This case describes a prune-belly syndrome patient who had a kidney
      transplantation and was diagnosed with Encapsulating Peritoneal Sclerosis (EPS),
      a rare but potentially fatal condition, mostly associated with Peritoneal
      Dialysis (PD). The definition of EPS is based on the clinical findings linked to
      bowel obstruction and on the demonstration of peritoneal thickening. Surgical
      treatment is the only established basic treatment for the condition. Prune-belly
      syndrome is characterized by the triad of deficient abdominal musculature,
      urinary tract abnormality and cryptorchidism. Because it is often associated with
      end-stage renal disease, PD is essential in the treatment of patients with prune
      belly syndrome. The aetiology of EPS follows a 'two-hit theory': the first 'hit'
      is peritoneal deterioration, caused by long-time exposure to PD. This causes
      peritoneal disruption which predisposes the patient to a second hit. In our
      patient, PD discontinuation and renal transplantation are possible 'second hits'
      that triggered the development of EPS. This case of prune-belly syndrome has all
      the necessary elements for the development of EPS, and we felt we should report
      it as the peroperative diagnosis was unexpected.

PMID- 20690524
TI  - Two cases of an embolized femoral closure device in the popliteal artery causing
      ischaemia.

PMID- 20690525
TI  - Treatment of symptomatic mobile aortic thrombus.
AB  - BACKGROUND: Mobile thoracic or abdominal aortic thrombi are a potential source of
      embolism to visceral organs or lower limbs. Detection levels of this type of
      aortic pathology after any embolic event have increased considerably.
      Nevertheless, therapeutic management of an intraluminal mobile thrombus of the
      aorta remains controversial. The aim of this study is to describe the treatment
      modalities for symptomatic mural aortic thrombi based on three cases diagnosed at
      our institution and to review the literature. METHODS: During the last decade,
      several patients with peripheral embolisation were diagnosed with an intraluminal
      mobile aortic thrombus. Three patients who were treated differently were selected
      and reviewed. In addition a literature search was performed on PubMed and Medline
      from their inception to the present for all English language articles using the
      following keywords: blue toe syndrome, peripheral arterial embolisation, mobile
      thrombus and aorta. The advantages and drawbacks of medical management, open and
      endovascular treatment are described. RESULTS: Three particular patients with
      embolisation due to a floating aortic thrombus were reviewed. The first patient
      underwent a thoracotomy with replacement of the descending thoracic aorta.
      Another case was treated successfully by implanting an endovascular stent graft
      in the descending thoracic aorta. The last patient was treated medically because
      of the involvement of the visceral vessels. When reviewing the literature, no
      randomised controlled trials were found but several case reports have described
      both open and endovascular techniques. No long-term follow up of this rare
      pathology is available. CONCLUSIONS: In the literature there is no consensus how
      to treat a symptomatic floating aortic thrombus. This report shows that
      therapeutic strategies are influenced by the localisation of the thrombus, the co
      morbidities of the patient and the physician' s preferences. Endovascular
      treatment in combination with high dose statins has become the preferred
      treatment method although long-term data are lacking.

PMID- 20690526
TI  - Gastrointestinal bleeding caused by a GIST of Meckel's diverticulum--a case
      report.
AB  - Meckel's diverticulum is a common congenital anomaly of the small intestine,
      affecting 2% of the population. Neoplastic transformation is infrequent and
      gastrointestinal stromal tumours are exceptional in this location. We report a
      case of gastrointestinal bleeding caused by a gastrointestinal stromal tumour of
      Meckel's diverticulum.

PMID- 20690527
TI  - Perforated jejunal diverticulitis: a rare presentation of acute abdomen.
AB  - Jejunal diverticulosis is a rare clinical finding with possible serious
      complications. A case of acute abdomen due to a perforated jejunal diverticulum
      is discussed, followed by a literature review concerning aetiology, symptoms,
      complications, diagnosis and treatment is provided.

PMID- 20690528
TI  - Isolated traumatic gallbladder rupture.
AB  - Blunt traumatic injury to the extrahepatic biliary system is a rare event usually
      recognized on evaluation and treatment of other visceral injuries during
      laparotomy. Isolated gallbladder rupture secondary to blunt abdominal trauma is
      even more uncommon, but poses a potential life-threatening surgical emergency.
      Delay in the diagnosis of the injury for several days due to no or vague symptoms
      and an insidious course are common. Early diagnosis is essential, as protracted
      treatment may result in significant morbidity and mortality. We report the case
      of a patient who suffered an isolated gallbladder rupture due to blunt abdominal
      trauma from a fall. The subject of isolated traumatic gallbladder rupture is
      reviewed because of the rarity of this condition and the diagnostic challenges it
      poses.

PMID- 20690529
TI  - The anterolateral thigh flap for complicated abdominal wall reconstruction after
      giant incisional hernia repair.
AB  - In the management of giant incisional hernias with loss of domain several
      surgical obstacles have to be addressed. Adequate coverage of the defect using
      mesh, sufficient local tissue advancement and prevention of wound and mesh
      infections are prerequisites for success. We present a case of a complicated
      giant incisional hernia repair after oncologic surgery, in which we chose for an
      intraabdominal mesh repair using a composite mesh. The patient developed a wound
      dehiscence and mesh infection, successfully treated with negative pressure
      therapy followed by a free ALT perforator flap. Several surgical techniques are
      discussed to manage these complicated hernias, such as progressive
      pneumoperitoneum, the component separation technique and the importance of soft
      tissue coverage (e.g. anterolateral thigh flap). In cases of wound complications,
      negative pressure therapy and new soft tissue coverage are discussed.

PMID- 20690530
TI  - Cross-femoral venous by-pass (Palma's procedure) to relieve venous hypertension
      due to retroperitoneal leiomyosarcoma: a case report.
AB  - Retroperitoneal leiomyosarcoma arising in, or involving, the inferior vena cava
      or the iliac vein are infrequent tumours. They are usually treated by "en-block"
      surgery. Venous reconstruction is usually not needed, since collateral
      circulation can adequately offset the main vessel flow. However, in rare cases,
      collateral circulation may be insufficient. The authors report a case of
      leiomyosarcoma infiltrating the left iliac vein. One week after radical resection
      surgery, the patient developed left leg compartmental syndrome due to venous
      hypertension. The patient was successfully treated by thrombectomy of the left
      femoral vein and cross-femoral venous bypass (Palma's Procedure) by means of an 8
      mm diameter polytetrafluoroethylene (PTFE) prosthesis. To improve the flow inside
      the graft, an arterio-venous fistula (AVF) was performed. The choice of a
      prosthetic conduit, its diameter, and the AVF are discussed.

PMID- 20690531
TI  - Giant presacral schwannoma mimicking malignancy in a man.

PMID- 20690532
TI  - A solid pseudopapillary tumour of the pancreas presenting after an abdominal
      trauma.
AB  - We present the case of 12-year-old girl who was referred with persistent
      abdominal pain and a palpable mass after blunt trauma and whose final diagnosis
      was a solid pseudopapillary tumour of the pancreas. This is the second case in
      our hospital of a solid pseudopapillary tumour of the pancreas presenting after a
      blunt abdominal trauma. Solid pseudopapillary tumour of the pancreas is a rare
      neoplasm. It comprises 2 to 3% of primary pancreatic tumours occurring at all
      ages. It was first described in 1959 by Frantz. The presenting symptoms are
      usually a slow growing abdominal mass with vague abdominal discomfort. Sometimes
      they are discovered after a trauma. Solid pseudopapillary tumours of the pancreas
      have a fairly characteristic appearance on imaging but the final diagnosis
      depends on histological confirmation. After resection the prognosis is excellent.

PMID- 20690533
TI  - Pseudoaneurysm of the supracoeliac aorta following blunt trauma in a 83-year-old
      woman.
AB  - We report on the case of an 83-year-old hemiplegic female patient presenting with
      post-traumatic pseudoaneurysm of the supracoeliac aorta, treated with 38 mm x 100
      mm Talent Endoluminal Stent-Graft (Medtronic Inc., Santa Rosa, CA) using local
      anaesthesia. The patient was discharged on day 3 and the 8 month follow-up was
      without complications.

PMID- 20690534
TI  - The abdominal cocoon: a rare cause of intestinal obstruction.
AB  - The abdominal cocoon is a very rare entity leading to bowel obstruction. A 30
      year-old man was admitted to the emergency department with symptoms and signs of
      mechanical intestinal obstruction. In addition to these, the recurrent episodes
      of obstruction in the patient's history and palpable abdominal mass found during
      the physical examination, appeared as important clinical characteristics of the
      pathology. A CT scan of the abdomen showed a conglomerate of bowel loops encased
      in a membrane. A Cocoon-like mass consisting of encapsulated bowel loops was the
      main finding of surgical exploration. Dissection and excision of the
      encapsulating membrane and release of encased loops provided definitive treatment
      of this rare entity.

PMID- 20690535
TI  - Metastasis from renal cell carcinoma presenting as skeletal muscle mass: a case
      report.
AB  - Renal cell carcinoma can metastasize to virtually any site. Skeletal muscle
      metastasis is not common. The correct diagnosis of metastatic renal cell
      carcinoma to skeletal muscle is difficult in comparison with soft-tissue
      metastasis diagnosis. We report the case of a 58-year-old man with skeletal
      muscle metastasis from a clear-type renal cell carcinoma 5 years after total
      nephrectomy. The tumour was located in the proximal left tight at the level of
      the great adductor muscle. Clinical work-up included both 18 fluorodeoxyglucose
      positron emission tomography combined with non-contrast computed tomography and
      magnetic resonance imaging. The mass was widely excised and was confirmed to be a
      metastasis from renal cell carcinoma. Maintaining a high degree of suspicion of
      metastatic renal cell carcinoma is required for patients with a history of renal
      cell carcinoma. Positron emission tomography, combined with computed tomography,
      appears to be an effective surveillance tool. Magnetic resonance imaging is
      helpful in the differential diagnosis from primary soft-tissue tumours.

PMID- 20690536
TI  - Novel combination combining J-Vac and VAC sponge for draining a rectal wound.
AB  - Active drains, which work by negative pressure, require a closed space for
      retaining the vacuum. Here the authors describe their novel technique of
      combining a J-Vac drain and the sponge of a vacuum assisted closure dressing pack
      to drain a rectal wound. This modification may be useful for rectal wounds and
      anastomotic leaks.

PMID- 20690537
TI  - Some notes on medical liability in ancient times.
AB  - Already in ancient times did medical liability occupy mankind. Various
      civilizations did give their own interpretation on the subject and proposed
      solutions. Original writings are rare and articles concerning ancient medical
      liability equally are hard to find. The only relatively trustworthy sources are
      of legal nature and find their origin in Greek philosophy and Roman Law. At a
      later stage, Arabic philosophers gave a renewed view on the statements of these
      previous civilizations and added their own way of thinking. All these influences
      still reflect in our modern western way of medical acting. Some of these ancient
      customs concerning medical liability will be discussed in this article.

PMID- 20690538
TI  - [Report on Salmonella isolates in livestock, food and feed, received at the
      German national reference laboratory for Salmonella during 2004-2008].
AB  - The German National Reference Laboratory for Salmonella receives Salmonella
      isolates from diverse laboratories in Germany. Most of the Salmonella strains
      originated from livestock and food.This report summarizes the studies of the
      German National Reference Laboratory on the prevalence of Salmonella ssp. in
      livestock, food and feed for the years 2004-2008. In the past five years, the
      National Reference Laboratory received 23,949 Salmonella isolates with S.
      enterica serovar Typhimurium and S. enterica serovar Enteritidis as the most
      prevalent serovars. In addition, we summarize the incidence of emerging serovars,
      such as S. enterica serovar Paratyphi B (d-tartrate positive), the monophasic
      variant of S. enterica serovar Typhimurium (S. enterica subspecies (subsp.)
      enterica serovar 1,4,[5],12:i:-) and S. enterica subsp. enterica serovar
      1,4,12:d:-.

PMID- 20690539
TI  - Evaluation of a commercial rabies ELISA as a replacement for serum neutralization
      assays as part of the pet travel scheme and oral vaccination campaigns of foxes.
AB  - EU Regulation 998/2003 requires the serological testing of rabies-vaccinated dogs
      and cats in approved laboratories using serum neutralization tests prior to
      movement of pet animals between certain EU member states and before pet animals
      are imported from unlisted third countries. Serum neutralisation tests are also
      used for measuring the efficacy of oral rabies vaccination programmes conducted
      in wild carnivore populations. In this study we evaluated an OIE-listed
      commercial ELISA as a potential replacement for serum neutralization assays under
      routine conditions as a diagnostic tool for both the serological testing of dog
      and cat sera as part of pet travel schemes and for follow-up investigations as
      part of oral vaccination campaigns. When dog and cat sera were analyzed by ELISA,
      a sensitivity compared to the standard serological test of 36.9-82.0% and 44.4
      88.9%, respectively, was calculated depending on the method used. For fox field
      samples from oral vaccination areas the sensitivity compared to the Rapid
      Fluorescent Focus Inhibition Test (RFFIT) was 32.4% (95% CI 24.8-40.0%). In its
      present format, the ELISA cannot replace standard serological assays neither in
      the pet travel scheme nor in follow-up investigations of oral vaccination
      campaigns. The results obtained resemble those of other rabies ELISAs recently
      evaluated for the same purpose and may therefore exemplify a general
      misconception (binding versus neutralization) in rabies serology rather than a
      failure of this ELISA test per se. Also, problems with technical and legislative
      issues associated with the serological testing of dog and cat sera for non
      commercial movement and related to the outcome of this study are addressed.

PMID- 20690540
TI  - New real-time reverse transcriptase polymerase chain reactions facilitate
      detection and differentiation of novel A/H1N1 influenza virus in porcine and
      human samples.
AB  - Influenza A viruses are maintained as a quasispecies cloud in several natural
      host reservoirs of avian as well as mammalian species. Accidental host exposure,
      selection and further adaptation of individual influenza A viruses during
      sporadic trans-species transmission may eventually lead to the establishment of
      new, stably circulating lineages in a new, possibly mammalian, host species.
      Given a high transmissibility of such a virus and a susceptible, immunologically
      naive population, pandemic spread of such viruses within a short time may ensue.
      In April 2009, a novel multi-reassortant influenza A virus of subtype H1N1 has
      emerged and regionally spread in humans in Mexico and the United States causing
      flu-like symptoms. Until June 2009 increasing levels ofa multiregional, global
      spread of this virus prompted the WHO to raise the pandemic alert to the highest
      level. Data from experimental infections in pigs as well as experience from
      natural outbreaks in swine farms world-wide have shown that porcine populations
      are fully susceptible to the new virus and are able to sustain uninterrupted
      transmission chains. A broad front incursion of the new human pandemic virus into
      the porcine population would have a significant negative impact on measures to
      restrict further spread of the virus in the human population.Therefore, sensitive
      tools for monitoring and detection of such an incursion in a timely manner are
      mandatory. We have developed two real-time RT PCRs which are specific for the
      hemagglutinin gene of the novel A/H1N1 virus and which allow detection of
      infected pigs with high sensitivity.These PCRs may become useful tools in future
      surveillance programmes.

PMID- 20690541
TI  - [Relationships between endogenous carnitine content and growth as carcass traits
      in swine].
AB  - In the present study on 29 growing female Deutsche Landrasse (DL) and Pietrain
      (Pi) pigs the relationship between endogenous carnitine content in plasma, in the
      blood lymphocytes and in the sceletal muscles with weight gain and carcass and
      meat quality is analysed. Significant correlations between carnitine content from
      rearing pigs to fattening pigs ((r)plasma rearing pig--plasma fattening pig =
      0.48, (r)lymphocytes rearing pig--plasma fattening pig = 0.69) reveal that
      indiviual differences in the endogenous carnitine content sustain over the growth
      phase. The aforementioned correlation reflects a moderate reproducibility
      reflecting a heritability in a wider sense. Over all breeds a negative relation
      between the carnitine content and the weight gain was detected.These correlations
      within the breeds Pi and DL are different. The correlations between weight gain
      and carnitine in lymphocytes for fattening pigs within DL (r = -0.53 to -0.68)
      are significantly different from zero. Furthermore correlations between the
      carnitine content of lymphocytes or plasma of fattening pigs and in the sceletal
      the endogen fatty acid transport system had a small effect on the weight gain and
      a moderate effect on the carcass and meat quality of pigs.

PMID- 20690542
TI  - Aromatase expression in the cerebellum of the dog infected with canine distemper
      virus.
AB  - Aromatase is the enzyme that catalyzes the biosynthesis of estrogens. It is
      implicated in neuroprotection.The present study investigated aromatase expression
      in the cerebellum of dogs infected with canine distemper virus (CDV), a disease
      characterized by demyelination in the white matter of the cerebellum. The
      presence of CDV infection was confirmed on the basis of histopathology and
      immunohistochemical localization of CDV antigen in glial cells of the white
      matter.The number of aromatase immunoreactive astrocytes were significantly (p <
      0.05) higher in CDV-infected dogs compared to control dogs. The results suggest
      that astrocytes respond to invasion and persistence of CDV by means of increased
      estrogen production.The results also suggest that the high level of estrogen
      expression is maintained similarly throughout all stages of the disease since the
      number of aromatase immunoreactive astrocytes did not vary during the different
      stages of CDV infection.

PMID- 20690543
TI  - The effect of chronic respiratory diseases on acute phase proteins and selected
      blood parameters of protein metabolism in calves.
AB  - This work was aimed at evaluation of the influence of chronic respiratory
      diseases on selected acute phase proteins (APPs), and on the concentrations of
      some parameters of protein metabolism in calves, as well as at evaluation of APPs
      as possible prognostic indicators in these diseases. We compared the results from
      27 sick calves with results from 15 clinically healthy calves. Blood samples were
      analysed for concentrations of haptoglobin (Hp), serum amyloid A (SAA), total
      proteins, albumin, urea, creatinine, and total immunoglobulins. In calves with
      chronic respiratory diseases we found significantly higher concentrations of Hp
      and SAA than in healthy animals (P < 0.001 and P < 0.01, respectively). Moreover,
      in sick calves, concentrations of these parameters were significantly higher in
      died or euthanised calves compared with calves in improved health status during
      therapy (P < 0.05 and P < 0.01, respectively). The concentrations of Hp in
      evaluated calves correlated significantly with the values of SAA (P < 0.001). In
      sick animals we found also significantly higher mean concentrations of total
      proteins and total immunoglobulins (P < 0.001 and P < 0.001, respectively), and
      significantly lower mean concentrations of albumin and creatinine (P < 0.01 and P
      < 0.01, respectively). Our findings show that in cases of chronic respiratory
      diseases, there is also an increased production of the mentioned APPs, and their
      evaluation could be useful in the determination of prognosis in sick calves.
      Moreover, the results suggest that these diseases could also significantly affect
      the concentrations of some other biochemical parameters. Thus, these results
      could be an important contribution to the possible laboratory diagnosis of
      respiratory problems in cattle.

PMID- 20690544
TI  - Histochemical profiles of mucins in the tracheal epithelium during the
      posthatching period of Japanese quail.
AB  - Mucus normally protects the airway epithelium from dehydration and inhaled
      infectious agents and possibly toxic substances. Two components of mucus, mucin
      and water play major roles in the elimination of inhaled foreign material. Mucins
      are large carbohydrates rich glycoprotein. The objective of the present study was
      to determine the histochemical changes in mucin pattern of the goblet cells and
      intraepithelial glands of the trachea in quails during the post-hatching period
      using specific various staining procedures for complex carbohydrates (Periodic
      acid Schiff, Alcian blue-Periodic acid Schiff (pH 2.5), Aldehyde fuchsin-Alcian
      blue (pH 2.5), High-iron diamine-Alcian blue (pH 2.5), Periodic acid
      Phenylhydrazine-Schiff). The intraepithelial alveolar glands were present at
      hatching and their numbers increased with the advance of age. In quail of all
      ages, the histochemical reactions revealed that the goblet cells and mucous cells
      of intraepithelial glands contained the mucins with vicinal diol groups, neutral
      mucin, sialomucin and sulphomucin. In all ages studied, the tracheal epithelium
      contained three distinct types of goblet or mucous cells producing neutral-, acid
      and mixture of neutral- and acid mucins. In 1 day old, the majority of the
      goblet cells and gland cells contained neutral mucin or a mixture of neutral- and
      acid mucins, while the proportion of only acid mucin-producing cells was few. The
      majority of acidic mucins consisted of sulphomucin. The sialomucin-containing
      cells were only a few. After day 14, it was seen that the content of sialomucin
      in the epithelium became more diffuse toward adulthood. In conclusion, the
      content of mucin of tracheal epithelium was variable depending on the ages during
      the post-hatching period. These changes in mucin dynamics could affect the
      protective functions against pathogens and toxins of the tracheal epithelium.

PMID- 20690545
TI  - Current developments in canine genetics.
AB  - In recent years, canine genetics had made huge progress. In 1999 the first
      complete karyotype and ideogram of the dog was published. Several linkage and RH
      maps followed. Using these maps, sets of microsatellite markers for whole genome
      scans were compiled. In 2003 the sequencing of the DNA of a female Boxer began.
      Now the second version of the dog genome assembly has been put online, and
      recently, a microchip SNP array became available. Parallel to these developments,
      some causal mutations for different traits have been identified. Most of the
      identified mutations were responsible for monogenic canine hereditary diseases.
      With the tools available now, it is possible to use the advantages of the
      population structure of the various dog breeds to unravel complex genetic traits.
      Furthermore, the dog is a suitable model for the research of a large number of
      human hereditary diseases and particularly for cancer genetics, heart and
      neurodegenerative diseases. There are some examples where it was possible to
      benefit from the knowledge of canine genetics for human research. The search for
      quantitative trait loci (QTL), the testing of candidate genes and genome-wide
      association studies can now be performed in dogs. QTL for skeletal size
      variations and for canine hip dysplasia have been already identified and for
      these complex traits the responsible genes and their possible interactions can
      now be identified.

PMID- 20690546
TI  - [Ground reaction forces of the canine hindlimb: are there differences between
      gait on treadmill and force plate?].
AB  - Computer assisted gait analysis is based on the evaluation of kinematic
      parameters and the measurement of ground reaction forces by force plates or
      special instrumented treadmills. So far it is unclear, whether the canine gait of
      the hind limb differs fundamentally between the walk on treadmill and force
      plate.Thus, aim of this study was the comparison of ground reaction forces of the
      hind limb of dogs while walking on force plate and treadmill. Nine adult dogs of
      different breeds were used in the study and one hind limb of each dog was
      analysed on force plate and treadmill.The peak forces in direction of x, y and z
      and the vertical impulse (IFz) were evaluated. Considering the ground reaction
      forces of the hind limb, despite of the breaking forces, there were no
      significant differences between force plate and treadmill. Comparison of peak
      vertical force (Fz) shows magnitudes of 61.58% BW (body weight) on the force
      plate and 51.87% BW on treadmill. Vertical impulse (IFz) mounts up to 10.23% BW
      on treadmill and 11.49% BW on force plate. Fx and Fy forces showed only a low
      correlation, so these values were considered as uncomparable between treadmill
      and force plate. In summary it can be concluded that the vertical ground reaction
      forces of the examined dogs do not differ fundamentally on force plate and
      treadmill, whereas certain differences exist with regard to mediolateral and
      craniocaudal ground reaction forces. In the context of clinical gait analysis
      studies instrumented treadmills can be used increasingly to support the
      diagnostics of orthopaedic problems. The results of this study suggest that a
      direct comparison of the treadmill data with force plate measurements is only
      meaningful for the vertical ground reaction forces.

PMID- 20690547
TI  - Pathologic fracture of the femur due to endometrial adenocarcinoma metastasis in
      a female pet rabbit (Oryctolagus cuniculi).
AB  - This case report describes the clinical, pathomorphological and histopathological
      findings in a 12-year-old female pet rabbit with a pathologic fracture of the
      femur due to a metastasising endometrial adenocarcinoma. The animal was presented
      due to a history of right hindlimb lameness and inappetence. A fracture of the
      right femur with adjacent lyric bone lesions was detected by clinical and X-ray
      examination. Necropsy and histopathology revealed an endometrial adenocarcinoma
      with metastasis to the right femoral bone, resulting in the pathologic fracture.
      In both locations, tumour cells were immunohistochemically positive for pan
      cytokeratin. Additionally, the animal suffered from an Encephalitozoon cuniculi
      infection which manifested itself in a multifocal granulomatous encephalitis and
      bilateral chronic inflammatory lesions in the kidneys.The report shows that in
      case of bone fractures in female pet rabbits the possibility of a pathologic
      fracture due to metastasising endometrial adenocarcinoma has to be considered.

PMID- 20690548
TI  - Human resources: The journey to the job of chief executive.

PMID- 20690549
TI  - Legal: Don't let stress strain relations.

PMID- 20690550
TI  - Human resources: A bridge too far?

PMID- 20690551
TI  - Innovation: Leaders are key to real progress.

PMID- 20690552
TI  - Almost five years later. Hurricane Katrina, New Orleans health care, and the
      Louisiana State University Health Sciences Center.

PMID- 20690553
TI  - Needlestick.

PMID- 20690554
TI  - Semmelweis: Magyar warrior.

PMID- 20690555
TI  - The inadequacy of legislative procedures and the infirmity of physician
      organizations.

PMID- 20690556
TI  - Direct-to-consumer advertising.

PMID- 20690557
TI  - Re "Getting drug money out of doctors' offices".

PMID- 20690558
TI  - Re "The ethics of cosmetic enhancement".

PMID- 20690559
TI  - Brohee Lecture at Gastro 2009. Acid secretion in the developed world--now too
      much of a good thing?

PMID- 20690560
TI  - A randomized, open-label, multicenter study evaluating the efficacy of
      peginterferon alfa-2a versus interferon alfa-2a, in combination with ribavirin,
      in naive and relapsed chronic hepatitis C patients.
AB  - BACKGROUND/AIMS: A large multicenter trial to compare the efficacy of
      peginterferon alfa-2a with interferon alfa-2a, in combination with ribavirin, in
      chronic hepatitis C patients. Efficacy data for prior relapsers are reported
      because treatment recommendations for this patient population are not well
      defined. PATIENTS AND METHODS: This study was a multicenter, prospective,
      randomized clinical trial. The primary efficacy endpoint was sustained virologic
      response in naive patients (n = 348) and relapsers (n = 95). RESULTS: Sustained
      virologic response rates were similar in naive patients and relapsers, both for
      non-pegylated and pegylated interferon (respectively 27 and 26% and 54 and 43%).
      Pegylated interferon given for 48 weeks did not improved the relapse rate: 15.9
      and 27.3% for non-pegylated and 16.7 and 30.4% for pegylated interferon, naive vs
      relapsers respectively. Stepwise logistic regression analysis revealed a
      significant association between slow response (detectable HCV RNA at week 12 and
      undetectable at week 24) and relapse in patients with an end-of-treatment
      response (55% versus 13% respectively; p = 0.02; odds ratio = 6.07). CONCLUSIONS:
      This trial confirms the value of using peginterferon alfa-2a in both naive and
      relapsed patients and provides support for a more tailored approach to treatment
      for relapsers and particulary for patients with a slow viral response.

PMID- 20690561
TI  - Hepatitis C genotype 4 response rate to pegylated interferon and ribavirin
      treatment in Belgium is similar to genotype 1.
AB  - BACKGROUND AND AIMS: Patients with genotype 4 (G4) chronic hepatitis C from the
      Middle East respond better to treatment than genotype 1 (G1) patients. There are
      few data on the response rates to treatment of G4 patients living in Western
      Europe. Many G4 patients in Belgium originate from Central Africa, and their
      response to treatment seems lower. METHODS: We analysed the data from 2
      randomized phase III studies conducted in Belgium, BerNar-1 and BerNar-2,
      comparing the sustained virological response (SVR) to pegylated interferon and
      ribavirin of 78 G4 patients (34 Caucasians, 44 Blacks) and 477 G1 patients (455
      Caucasians, 12 Blacks), and assessing the predictors of SVR. RESULTS: Baseline
      characteristics of G4 and G1 patients were similar except mainly for race.
      Complete early virological response (cEVR) was similar in G4 (73.2%) and G1
      (68.1%). cEVR was also similar between Black and Caucasian G4 and between Black
      and Caucasian G1 patients. Partial early virological response was similar for G4
      and G1. SVR was similar for G4 (51.3%) and G1 (51.8%). There was a trend for a
      higher SVR in Caucasians than in Blacks. In multivariate analysis, the only
      predictors for SVR were the presence of cirrhosis, HCV viral load, age < 40 vs >
      or = 40 yrs, and treatment status (relapsers vs naive). CONCLUSIONS: G4 patients
      in Belgium have the same SVR as G1 patients. It is lower than the SVR described
      in Arab countries, especially for Black G4 patients.

PMID- 20690562
TI  - Helicobacter pylori virulence factors and their role in peptic ulcer diseases in
      Turkey.
AB  - BACKGROUND AND STUDY AIMS: The role of virulence factors present in Helicobacter
      pylori (H. pylori) strains and the characterization of such factors being
      predictive of specific disease is still not clear. In this study, the cagA, vacA
      alleles and the recently characterized vacA i-region and dupA and their
      association with the severity of the disease was determined. PATIENTS AND
      METHODS: Antral biopsies from 91patients with peptic ulcer (PU) (n = 41),
      gastritis (n = 48) and gastric cancer (GC) (n = 2) were analyzed for the presence
      of H. pylori by the CLO-test and PCR. A 79/91 (86%) patients were positive for H.
      pylori by either PCR or by both PCR and CLO-test. PCR-based typing of H. pylori
      isolates was performed on DNA extracted directly from biopsy samples. RESULTS:
      The cagA+ strains were found more likely to be associated with vacA s1 than s2.
      The vacA i1 allele detected in 16/23 (70%) of samples had significant association
      with duodenal ulcers than those 16/37 (44%) of gastritis (P < 0.04). No
      significant association was found between dupA and duodenal ulcer. This study
      provided more evidence that the vacA i1 allele is one of the virulence factors of
      H. pylori that had significant association with severe outcome.

PMID- 20690563
TI  - Autoimmune pancreatitis and extrapancreatic manifestations of IgG4-related
      sclerosing disease.
AB  - In a review of the literature concerning autoimmune pancreatitis we had special
      interest for the concept of IgG4-related pathology as a systemic disease with
      several clinical manifestations. In general, IgG4-positivity can not only be
      found in the pancreas, but also at the level of the kidneys, extrahepatic biliary
      ducts, gallbladder, lungs, salivary glands, lacrimal glands, retroperitoneal
      tissue, ureters, prostate, meninges and lymph nodes. IgG4 seems to be a central
      key player in the pathophysiology of this disease.

PMID- 20690564
TI  - Risk for relapse of alcohol use after liver transplantation for alcoholic liver
      disease: a review and proposal of a set of risk assessment criteria.
AB  - BACKGROUND: Liver transplantation for end stage alcoholic liver disease is
      becoming an increasingly frequent procedure. Within this context assessing the
      risk on relapse in alcohol use is a major issue. However, up to now, there is a
      clear lack in validated criteria that can be used to assess future relapse risk.
      METHOD: Literature review based upon Medline search identifying all new studies
      that have been published after the latest meta-analysis on this subject (2007
      2009). RESULTS: Five new original studies were identified. They provide new
      evidence for the prospective validity of different criteria; pretransplant
      abstinence duration, diagnosis of alcohol dependence versus abuse, level of
      social support, additional psychiatric co morbidity. CONCLUSIONS: These criteria
      seem promising as to the prediction of relapse in alcohol after
      livertransplantation. Based upon these results a new comprehensive assessment
      scale is proposed.

PMID- 20690565
TI  - Retroperitoneal, mesenteric and multifocal fibrosis: review of their
      aetiopathogenesis. A possible role of adipocytes as in Crohn's disease?
AB  - First observed during an autopsy by Simpson in 1867 as a cause of hydronephrosis,
      retroperitoneal fibrosis became a medical topic after the detailed report of two
      cases by Ormond in 1948. Initially considered to be chiefly an urological
      disease, it appeared progressively that it could possibly be a systemic disease
      because of its occasional association with inflammatory fibrosing processes in
      other sites of the body or with clinical and biological manifestations of
      hypersensitivity or autoimmunity. Mesenteric panniculitis and mesenteric fibrosis
      may occur independently or, occasionally, in association with retroperitoneal
      fibrosis. One third of the cases of retroperitoneal fibrosis can be attributed to
      specific causes. That the other cases (idiopathic retroperitoneal fibrosis) could
      be manifestations of an immunological (systemic) process with vasculitis is
      generally accepted. The authors present a survey of the various possible
      morphological aspects of the disease and a review of its aetiopathogenesis.
      Idiopathic retroperitoneal fibrosis is usually characterized by an overproduction
      of fibro-inflammatory tissue; however in few cases as well as in mesenteric
      panniculitis, extensive development of fatty tissue may also occur. The authors
      suggest that an initial proliferation of adipocytes, considered to account for
      the fat hyperplasia adjacent to Crohn's ileitis, could also play a role in the
      pathogenesis of the inflammatory fibrosing process in some cases of mesenteric
      and retroperitoneal fibrosis.

PMID- 20690566
TI  - Management of metabolic syndrome and associated cardiovascular risk factors.
AB  - Patients with metabolic syndrome have a 1.5- to 3-fold increase in the risk of
      coronary heart disease and stroke. The association between metabolic syndrome and
      cardiovascular diseases raises important questions about the underlying
      pathological processes, especially for designing targeted therapeutic
      interventions. Cardiovascular risk reduction in individuals with metabolic
      syndrome should include at least three levels of interventions: 1) control of
      obesity, unhealthy diet and lack of physical activity; 2) control of the
      individual components of metabolic syndrome, especially atherogenic
      dyslipidaemia, hypertension, dysglycaemia and prothrombotic state; and 3) control
      of insulin resistance, a defect closely linked to metabolic syndrome. Metabolic
      syndrome generally precedes and is often associated with type 2 diabetes. Because
      of this intimate relationship, appropriate management of metabolic syndrome
      should be able to prevent the progression from impaired glucose tolerance to
      frank diabetes and thus to prevent type 2 diabetes, another important
      cardiovascular risk factor. The importance of prevention of diabetes in high-risk
      individuals (such as people with metabolic syndrome are) is highlighted by the
      substantial and worldwide increase in the prevalence of type 2 diabetes in recent
      years. Owing to the complex pathophysiology and phenotypic expression of
      metabolic syndrome, lifestyle changes are crucial as they are able to positively
      and simultaneously influence almost all components of the syndrome. If such
      measures are not sufficient or not adequately followed, a pharmacological
      intervention may be considered. However, no official guidelines are available yet
      concerning the pharmacological management of individuals with metabolic syndrome.

PMID- 20690567
TI  - Involvement of the gut microbiota in the development of low grade inflammation
      associated with obesity: focus on this neglected partner.
AB  - Nowadays, the literature provides evidence that obesity, type 2 diabetes and
      insulin resistance are characterized by a low grade inflammation. Among the
      environmental factors involved in such diseases, the gut microbiota has been
      proposed as a key player. This neglected "organ" has been found to be different
      between healthy and or obese and type 2 diabetic patients. For example, recent
      data have proposed that dysbiosis of gut microbiota (at phyla, genus, or species
      level) affects host metabolism and energy storage. Among the mechanisms,
      metabolic endotoxemia (higher plasma LPS levels), gut permeability and the
      modulation of gut peptides (GLP-1 and GLP-2) have been proposed as putative
      targets. Here we discuss 1 degrees the specific modulation of the gut microbiota
      composition by using prebiotics and 2 degrees the novel findings that may explain
      how gut microbiota can be involved in the development or in the control of
      obesity and associated low-grade inflammation.

PMID- 20690568
TI  - Papillary adenoma of the extrahepatic biliary tract--a rare cause of obstructive
      jaundice.
AB  - The authors present a case of papillary adenoma of the extrahepatic biliary tract
      presenting as obstructive jaundice. The diagnosis was based on the endoscopic
      retrograde cholangiopancreatography (ERCP), and above all cholangioscopy
      findings. The patient was treated by bile duct resection with Roux-en-Y
      hepaticojejunostomy. Adenoma of the bile duct is a rare entity. Only a few cases
      have been described in the world literature so far.

PMID- 20690569
TI  - Management of rectal foreign bodies.
AB  - The presence of foreign bodies inserted into the rectum is not an uncommon
      situation. Precise guidelines for the management and extraction of these foreign
      bodies are not frequently described in the literature. Anal access, whether
      endoscopic or surgical, varies depending on the type of foreign bodies, their
      size and morphology, and their location in the lower digestive tract In this
      report, we describe a case of three rectal foreign bodies that necessitated a
      mixed endoscopic and surgical approach, and provide a review of the literature.

PMID- 20690570
TI  - Liver tuberculosis mistaken for malignancy. The role of needle biopsy.
AB  - Despite advances in imaging techniques rare or atypical liver lesions still pose
      a diagnostic challenge. In many centres percutaneous fine needle aspiration
      cytology or biopsy is routinely performed in order to obtain a definitive
      diagnosis. However because of the risk of tumour seeding along the needle tract
      this attitude may jeopardize the patient's chances for cure in case of
      malignancy. The role of percutaneous liver biopsy is reappraised in the light of
      an observation in which major hepatectomy was performed for suspected neoplasia
      only to discover at pathology that the lesion was a benign tuberculosis
      pseudotumour.

PMID- 20690571
TI  - Primary aortoenteric fistula caused by an infected abdominal aortic aneurysm with
      Mycobacterium avium complex in an HIV patient.
AB  - Primary aortoenteric fistula (PAEF) is a rare but complex clinical entity
      requiring multimodality approach for diagnosis and treatment. We report the first
      ever case of upper gastrointestinal (UGI) hemorrhage caused by an aortoenteric
      fistula (AEF) secondary to Mycobacterium avium complex (MAC) in a patient with
      human immunodeficiency virus (HIV) infection. Esophagogastroduodenoscopy (EGD)
      showed an ulcer in the distal duodenum and a computed tomography (CT) scan
      confirmed a contained abdominal aortic aneurysm (AAA) rupture with an aorto
      enteric fistula communicating with the third portion of the duodenum. Emergent
      surgery was undertaken which was lifesaving. A high index of suspicion, early
      diagnosis and prompt surgical intervention are crucial for survival of patient
      with PAEF.

PMID- 20690572
TI  - Zinc and biotin deficiencies after pancreaticoduodenectomy.
AB  - We report zinc and biotin deficiencies after pancreaticoduodenectomy in a 16 year
      old female presenting clinically with marked alopecia, total body hair loss, dry
      skin with scales, and maculopathy with significant vision loss. These
      micronutrient deficiencies likely occurred due to resection of the duodenum and
      proximal jejunum, sites of primary absorption of several micronutrients and their
      protein carriers, including zinc and biotin. Early diagnosis is essential to
      prevent irreversible sequelae. Adequate supplementation of zinc and biotin as
      well as dietary advice is needed for clinical improvement.

PMID- 20690573
TI  - Megaduodenum: an unusual presentation of amyloidosis?
AB  - Amyloidosis, a potentially fatal disease, is characterized by an abnormal
      deposition of autologous proteins. Heart, liver, kidneys, lung, thyroid, skin and
      the gastrointestinal tract can be involved; in this last case mucosal alterations
      or disturbances of the motility leading to pseudo-obstruction, bleeding, diarrhea
      and malabsorption can be present. However, the data concerning the possible
      gastrointestinal presentations of amyloidosis are scanty and heterogeneous. We
      report the case of a patient presenting severe gastrointestinal symptoms caused
      by a megaduodenum. The patient was thoroughly investigated and lesions appeared
      limited to the upper gastrointestinal tract in the absence of a systemic
      disorder. However, at follow up the patient developed cardiac dilatation and
      bioptic samples revealed the presence of amyloidosis.

PMID- 20690574
TI  - Ornidazole-induced hepatitis.

PMID- 20690575
TI  - The prevalence of gallbladder polyps is higher in HBsAg positive population.

PMID- 20690576
TI  - Insulinoma and extreme obesity in a patient with MEN1 syndrome.

PMID- 20690577
TI  - Human resources: Who are you calling junior?

PMID- 20690578
TI  - Community interest: Plugging the inequality gaps with prevention.

PMID- 20690579
TI  - Human resources: The test of a true leader.

PMID- 20690580
TI  - This cord could save a life.

PMID- 20690581
TI  - Come and get IT.
AB  - With the release of final rules on meaningful use, the race is on for hospitals
      to invest in IT systems that meet the new criteria. But some, while praising the
      plan, see a big flaw: Some hospitals with multiple campuses that operate under
      one Medicare provider number will receive less money than multiple-hospital
      systems with a comparable bed count. "It's about a $25 million hit to
      Montefiore," says Montefiore Medical Center CEO Steven Safyer.

PMID- 20690582
TI  - Relieved over relaxed rules. Vendors say final regulations are less cumbersome.

PMID- 20690584
TI  - It's your turn. We interrupt this regularly scheduled editorial to bring you
      readers' thoughts.

PMID- 20690583
TI  - Don't ask, don't tell. A third of physicians in a study don't feel obliged to
      report impaired docs.

PMID- 20690585
TI  - Largest healthcare services mergers/acquisitions in 2009. Completed or pending
      U.S. transactions ranked by deal's price.

PMID- 20690586
TI  - Two-dimensional heterospectral correlation analysis of X-ray photoelectron
      spectra and infrared spectra for spin-coated films of biodegradable poly(3
      hydroxybutyrate-co-3-hydroxyhexanoate) copolymers.
AB  - We investigated the thermal behavior of spin-coated films of biodegradable poly(3
      hydroxybutyrate-co-3-hydroxyhexanoate) (P(HB-co-HHx)) copolymers at the molecular
      level. To better understand details of thermal behavior of spin-coated films of
      P(HB-co-HHx) copolymers, we applied two-dimensional (2D) correlation analysis to
      the spectra of P(HB-co-HHx) (HHx = 12.0, 10.0, and 3.8 mol %) copolymers during
      the heating process from 30 to 150 degrees C as obtained by temperature-dependent
      infrared-reflection absorption spectroscopy and X-ray photoelectron spectroscopy
      (XPS). 2D IR and 2D XPS correlation spectra of spin-coated films of P(HB-co-HHx)
      copolymers clearly revealed the sequence of intensity changes with increasing
      temperature: an amorphous band increases first and then a band for less ordered
      secondary crystals decreases before a band for well-ordered primary crystals.
      Furthermore, the synchronous 2D heterospectral XPS/IR correlation spectrum
      elucidated the correlation between the IR and XPS bands, confirming their band
      assignments. The asynchronous 2D heterospectral correlation spectrum revealed the
      probe-dependent asynchronicity between XPS and IR signals arising from the same
      species even under identical perturbation conditions because of the different
      scales of molecular changes probed. It clearly provides a complete interpretation
      of the phase transition phenomenon of P(HB-co-HHx) copolymers, which could not
      have been obtained through XPS or IR study alone, and also, the results obtained
      thereof offer a new insight into the molecular interactions as well observed by
      two different probes.

PMID- 20690587
TI  - Structural and functional studies of WlbA: A dehydrogenase involved in the
      biosynthesis of 2,3-diacetamido-2,3-dideoxy-D-mannuronic acid .
AB  - 2,3-Diacetamido-2,3-dideoxy-d-mannuronic acid (ManNAc3NAcA) is an unusual dideoxy
      sugar first identified nearly 30 years ago in the lipopolysaccharide of
      Pseudomonas aeruginosa O:3a,d. It has since been observed in other organisms,
      including Bordetella pertussis, the causative agent of whooping cough. Five
      enzymes are required for the biosynthesis of UDP-ManNAc3NAcA starting from UDP-N
      acetyl-d-glucosamine. Here we describe a structural study of WlbA, the NAD
      dependent dehydrogenase that catalyzes the second step in the pathway, namely,
      the oxidation of the C-3' hydroxyl group on the UDP-linked sugar to a keto moiety
      and the reduction of NAD(+) to NADH. This enzyme has been shown to use alpha
      ketoglutarate as an oxidant to regenerate the oxidized dinucleotide. For this
      investigation, three different crystal structures were determined: the enzyme
      with bound NAD(H), the enzyme in a complex with NAD(H) and alpha-ketoglutarate,
      and the enzyme in a complex with NAD(H) and its substrate (UDP-N-acetyl-d
      glucosaminuronic acid). The tetrameric enzyme assumes an unusual quaternary
      structure with the dinucleotides positioned quite closely to one another. Both
      alpha-ketoglutarate and the UDP-linked sugar bind in the WlbA active site with
      their carbon atoms (C-2 and C-3', respectively) abutting the re face of the
      cofactor. They are positioned approximately 3 A from the nicotinamide C-4. The
      UDP-linked sugar substrate adopts a highly unusual curved conformation when bound
      in the WlbA active site cleft. Lys 101 and His 185 most likely play key roles in
      catalysis.

PMID- 20690588
TI  - A multiple shock tube and chemical kinetic modeling study of diethyl ether
      pyrolysis and oxidation.
AB  - The pyrolysis and oxidation of diethyl ether (DEE) has been studied at pressures
      from 1 to 4 atm and temperatures of 900-1900 K behind reflected shock waves. A
      variety of spectroscopic diagnostics have been used, including time-resolved
      infrared absorption at 3.39 mum and time-resolved ultraviolet emission at 431 nm
      and absorption at 306.7 nm. In addition, a single-pulse shock tube was used to
      measure reactant, intermediate, and product species profiles by GC samplings at
      different reaction times varying from 1.2 to 1.8 ms. A detailed chemical kinetic
      model comprising 751 reactions involving 148 species was assembled and tested
      against the experiments with generally good agreement. In the early stages of
      reaction the unimolecular decomposition and hydrogen atom abstraction of DEE and
      the decomposition of the ethoxy radical have the largest influence. In separate
      experiments at 1.9 atm and 1340 K, it is shown that DEE inhibits the reactivity
      of an equimolar mixture of hydrogen and oxygen (1% of each).

PMID- 20690589
TI  - Enantioselective adsorption of surfactants monitored by ATR-FTIR.
AB  - The selectivity of adsorption of chiral surfactants to a chiral monolayer at the
      solid-liquid interface was studied using attenuated total reflection Fourier
      transform infrared spectroscopy (ATR-FTIR). One enantiomer of the chiral
      surfactant was deuterated, which causes a change in the IR absorption frequency,
      and allows independent measurement of the adsorption of each molecule. Both the
      surfactant, N-lauroyl phenylalanine (NLP), and the chiral monolayer, N-L
      phenylalaninoyl, 11-undecyl-silicon, were amino acid derivatives. An enantiomeric
      excess of 56 +/- 22% of the L over D was observed for adsorption to the interface
      between a carbon tetrachloride solution containing a quasi-racemate of N-lauroyl
      phenylalanine and the N-L-phenylalaninoyl, 11-undecyl monolayer film on silicon.
      In contrast, equimolar adsorption occurred from an equimolar mixture of
      hydrogenated and deuterated forms of the L surfactant. The measured enantiomeric
      excess strongly depended on the density of chiral surface groups: the higher the
      density of chiral groups on the surface, the better the enantiodiscrimination,
      even though the total adsorption was roughly constant. This nonlinear behavior
      indicates that more than one chiral surface group is required for significant
      selectivity.

PMID- 20690590
TI  - Effect of superhydrophobicity on the barrier properties of polymethylene films.
AB  - Superhydrophobic polymethylene (PM) films provide remarkable protection against
      the transport of aqueous redox probes as a result of entrapped air at the
      water/polymer interface. The wetting properties and the topography for a set of
      superhydrophobic (SH) and nonsuperhydrophobic (NSH) PM films were established to
      compare their interfacial behavior using electrochemical impedance spectroscopy
      (EIS). EIS results show that SH PM films exhibit resistances against ion transfer
      that are approximately 3 orders of magnitude higher than those of NSH PM films.
      Rationalization of these results in the context of the Helmholtz theory reveals
      that the imaginary impedance or inverse capacitance of SH PM films exhibits
      positive deviations from that predicted by Helmholtz theory for smooth PM films.
      Here, we model the capacitance behavior of a SH film as a PM/air composite that
      acts as a circuit of capacitors. The resulting mathematical model of this
      analysis enables correlation of the effective dielectric properties of the film
      (d(effective), epsilon(effective)) to measurable properties such as thickness
      (d(film)) and the dielectric constant (epsilon(PM)) of the PM film. Finally, a
      sensitivity analysis shows that the limited contact area between the aqueous
      solution and PM in SH films is the primary reason for the enhancement in the
      barrier properties of the film.

PMID- 20690591
TI  - Protein matrices for improved wound healing: elastase inhibition by a synthetic
      peptide model.
AB  - The unique properties of silk fibroin were combined with keratin to develop new
      wound-dressing materials. Silk fibroin/keratin (SF/K) films were prepared to
      reduce high levels of elastase found on chronic wounds. This improved biological
      function was achieved by the incorporation of a small peptide synthesized based
      on the reactive-site loop of the Bowman-Birk Inhibitor (BBI) protein. In vitro
      degradation and release were evaluated using porcine pancreatic elastase (PPE)
      solution as a model of wound exudate. It was found that biological degradation
      and release rate are highly dependent on film composition. Furthermore, the level
      of PPE activity can be tuned by changing the film composition, thus showing an
      innovative way of controlling the elastase-antielastase imbalance found on
      chronic wounds.

PMID- 20690592
TI  - Cationic liposome colloidal stability in the presence of guar derivatives
      suggests depletion interactions may be operative in artificial tears.
AB  - The colloidal stability of cationic 1,2-dioleoyl-3-trimethylammonium-propane
      (DOTAP) liposomes was measured in the presence of guar, carboxymethyl guar,
      hydroxypropyl guar (HPG), and in mixtures of HPG with boric acid. Carboxymethyl
      guar induced DOTAP aggregation, presumably by bridging flocculation. The
      interaction with HPG-borate, an anionic polyelectrolyte with labile charge
      groups, depended on ionic strength. Without added salt, HPG-borate (pH 9.2)
      adsorbed on the liposomes and destabilized them. In contrast, in 0.1 M NaCl, HPG
      borate did not adsorb onto the liposomes. HPG, HPG-borate, and guar induced
      depletion flocculation of the liposomes at high polymer concentration. Depletion
      flocculation may be an important mechanism when HPG is employed in artificial
      tear formulations.

PMID- 20690593
TI  - Hydrodynamic versus size exclusion chromatography characterization of alternan
      and comparison to off-line MALS.
AB  - Alternan is an ultrahigh molar mass polysaccharide composed of alternating alpha
      (1->3) and alpha-(1->6) repeat units and that also possesses long-chain
      branching. Its molar mass distribution (MMD) can extend into the hundreds of
      millions of grams per mole. Characterizing alternan by means of size exclusion
      chromatography (SEC) is a lengthy process and an incomplete one because even
      under the best possible experimental conditions, the polysaccharide appears to
      degrade during its passage through the SEC columns. As an alternative to SEC, we
      have investigated the use of hydrodynamic chromatography (HDC) as a possible
      characterization technique for alternan. Results from packed-column HDC with
      multiangle static light scattering (MALS) detection compare favorably to results
      from off-line MALS analysis, and HDC results are obtained in a fraction of the
      time needed for SEC. The largest molar mass alternan did appear to undergo some
      degradation during HDC as a result of interstitial stresses in the column bed.
      This could be remedied by the use of columns with larger packing particles.
      Evidence of long-chain branching in alternan is provided via a comparison of the
      intrinsic viscosities and viscometric radii of the polysaccharide to those of a
      pullulan standard and of a theoretical pullulan of molar mass equal to those of
      the alternans examined.

PMID- 20690594
TI  - Fabrication of cross-linked polyethyleneimine microfibers by reactive
      electrospinning with in situ photo-cross-linking by UV radiation.
AB  - The objective of this work is to demonstrate the feasibility of fabrication of
      cross-linked polyethyleneimine microfibers by a reactive photo-electrospinning
      technology. Linear polyethyleneimine (L-PEI) has been grafted with cross-linkable
      methacrylate moiety by reaction with glycidyl methacrylate (GMA), enabling the
      polymer to cross-link upon UV exposure. The photo-cross-linking reaction was
      characterized by a photo-rheometer. Neat L-PEI or methacrylated L-PEI tends to
      aggregate rendering it very difficult to electrospin into microfibers. A high
      molecular weight polyvinylpyrrolidone (PVP) is an efficient chain entanglement
      enhancer for both L-PEI and methacrylated L-PEI and helpful to maintain fibrous
      structure. An optimized composition consisted of 10% methacrylated L-PEI (less
      than 14.8% methacrylation of total L-PEI) combined with 2% PVP and 1%
      photoinitiator in ethanol was successfully electrospun into smooth cross-linked
      microfibers using the reactive electrospinning device. Diameters of cross-linked
      fibers can be controlled from 419 nm to 2 MUm depending on methacrylation degree
      and UV irradiation intensity. The resultant cross-linked L-PEI microfibers have
      demonstrated significantly improved solvent resistance, thermal stability, and
      mechanical properties. The distinguished characteristics of this novel reactive
      electrospinning technology are the high cross-linking efficiency and minimal
      toxic chemical residues in the products. The stability of the fibers can be
      readily modified and controlled by the cross-linking degree, which is of great
      importance for biomedical applications.

PMID- 20690595
TI  - Copper-catalyzed aerobic oxidative functionalization of an arene C-H bond:
      evidence for an aryl-copper(III) intermediate.
AB  - Recent studies have highlighted the ability of Cu(II) to catalyze the aerobic
      oxidative functionalization of C-H bonds; however, very little is known about the
      mechanisms of these reactions. Here, we describe the Cu(II)-catalyzed C-H
      methoxylation and amidation of a macrocylic arene substrate with O(2) as the
      stoichiometric oxidant. Kinetic and in situ spectroscopic studies demonstrate the
      involvement of three different oxidation states of Cu in the catalytic mechanism,
      including an aryl-Cu(III) intermediate. These observations establish a novel
      mechanistic pathway that has implications for numerous other Cu-catalyzed aerobic
      oxidation reactions.

PMID- 20690596
TI  - Brightly luminescent organically capped silicon nanocrystals fabricated at room
      temperature and atmospheric pressure.
AB  - Silicon nanocrystals are an extensively studied light-emitting material due to
      their inherent biocompatibility and compatibility with silicon-based technology.
      Although they might seem to fall behind their rival, namely, direct band gap
      based semiconductor nanocrystals, when it comes to the emission of light, room
      for improvement still lies in the exploitation of various surface passivations.
      In this paper, we report on an original way, taking place at room temperature and
      ambient pressure, to replace the silicon oxide shell of luminescent Si
      nanocrystals with capping involving organic residues. The modification of surface
      passivation is evidenced by both Fourier transform infrared spectroscopy and
      nuclear magnetic resonance measurements. In addition, single-nanocrystal
      spectroscopy reveals the occurrence of a systematic fine structure in the
      emission single spectra, which is connected with an intrinsic property of small
      nanocrystals since a very similar structure has recently been observed in
      specially passivated semiconductor CdZnSe nanoparticles. The organic capping also
      dramatically changes optical properties of Si nanocrystals (resulting ensemble
      photoluminescence quantum efficiency 20%, does not deteriorate, radiative
      lifetime 10 ns at 550 nm at room temperature). Optically clear colloidal
      dispersion of these nanocrystals thus exhibits properties fully comparable with
      direct band gap semiconductor nanoparticles.

PMID- 20690597
TI  - Tracing natural and anthropogenic Pb in sediments along the Mediterranean Coast
      of Israel using Pb isotopes.
AB  - The natural and anthropogenic sources of Pb in surface sediments offshore the
      Israeli Mediterranean coast were studied using the isotopic composition of Pb in
      diluted acid sediment extracts. Surface sediments were collected at the lower
      reaches of coastal streams, along a south-north offshore transect and at selected
      monitoring stations of the Dan Region Wastewater Plant (DRWP) outfall pipe. The
      background values of the Pb isotopic composition were determined from the deepest
      part of two representative cores collected offshore and were found to have a
      narrow range dominated mainly by clays derived from both inland soils and the
      Nilotic cell and to a lesser extent from the Saharan dust. The impact of the DRWP
      activated sludge can be traced to a distance of ca. 2 km from the outfall pipe.
      Enrichment factors of Zn, Cu, and Pb were up to 25 and are strongly correlated
      with each other and with the Pb isotopic composition, thus demonstrating the
      sludge to be their common source. The isotopic compositions of Pb in stream
      sediments have the widest range of values and indicate a strong anthropogenic
      contribution, probably from both post-1992 aerosols and point sources. However
      the impact of stream sediments on marine sediments could not be clearly detected.

PMID- 20690599
TI  - Water confinement in hydrophobic nanopores. Pressure-induced wetting and drying.
AB  - Wetting and drying of hydrophobic pores with diameters lower than 0.2 MUm by
      aqueous solutions at different hydrostatic pressures is investigated by measuring
      the ionic conductance variation through the nanopores. The critical pressure for
      water intrusion into the nanopores increases with lowering the pore diameter and
      the surface tension of the hydrophobic modification, in agreement with the
      Laplace equation. Nevertheless, restoring the pressure to the atmospheric one
      does not result in spontaneous pore dewetting unless bubbles are left inside the
      pores. Such bubbles can appear at the regions of narrowing cross section and/or
      varying quality of the hydrophobic modification and thus can be engineered to
      control water expulsion.

PMID- 20690598
TI  - Plasmon-resonant nanoparticles and nanostars with magnetic cores: synthesis and
      magnetomotive imaging.
AB  - Plasmon-resonant gold nanostars (NSTs) with magnetic cores were synthesized by a
      multistep sequence from superparamagnetic Fe3O4 nanoparticles (NPs) and evaluated
      as optical contrast agents under magnetomotive (MM) imaging conditions. Core
      shell Fe3O4@Au NPs were prepared in nonpolar organic solvents with nanometer
      control over shell thickness and with good epitaxy to the Fe3O4 surface.
      Anisotropic growth was performed in micellar solutions of cetyltrimethylammonium
      bromide (CTAB) under mildly reducing conditions, resulting in NSTs with physical
      features similar to those produced from colloidal gold seeds. NSTs could be
      produced below 100 nm from tip to tip, but seed size had a significant impact on
      growth habit, with larger seed particles producing submicrometer-sized "morning
      stars". Both NSTs and aggregated core-shell NPs are responsive to in-plane
      magnetic field gradients and can provide enhanced near-infrared (NIR) contrast
      under MM conditions, but do so by different mechanisms. NSTs can modulate
      polarized NIR scattering with minimal translational motion, giving the appearance
      of a periodic but stationary "blinking", whereas core-shell NP aggregates require
      lateral displacement for signal modulation. The polarization-sensitive MM imaging
      modality offers the dual advantage of enhanced signal quality and reduced
      background signal and can be applied toward the detection of magnetomotive NSTs
      in heterogeneous biological samples, as illustrated by their detection inside of
      granular cells such as macrophages.

PMID- 20690601
TI  - Copper-catalyzed Ficini [2 + 2] cycloaddition of ynamides.
AB  - The Ficini [2 + 2] cycloaddition using N-sulfonyl-substituted ynamides is
      described, featuring the utility of CuCl(2) and AgSbF(6) as catalysts. This work
      represents the first successful example of ynamides participating in a thermal [2
      + 2] cycloaddition with enones.

PMID- 20690602
TI  - Arrested 1,2-hydrogen migration from silicon to nickel upon oxidation of a three
      coordinate Ni(I) silyl complex.
AB  - Reaction of the dimeric Ni(I) chloride complex [(dtbpe)NiCl](2) (1) with
      dimesitylsilyl potassium affords the three-coordinate Ni(I) silyl complex
      (dtbpe)Ni(SiHMes(2)) (2). Alternatively, 2 can be prepared by an oxidative
      addition reaction of Mes(2)Si(H)OTf (Tf = CF(3)SO(3)) with the nickel(0) complex
      [(dtbpe)Ni](2)(mu-C(6)H(6)) (3), with (dtbpe)Ni(OTf) (4) formed as an easily
      separable byproduct. The one-electron oxidation of 2 by ferrocenium affords
      diamagnetic [(dtbpe)Ni(mu-H)SiMes(2)][BAr(F)(4)] (5), a Ni(II) complex formed by
      partial 1,2-H migration from silicon to nickel and featuring an unusual 3-center,
      2-electron bonding motif between Ni, Si, and the bridging H. Complex 5 was also
      obtained from Mes(2)SiH(2) activation by the neopentyl complex salt
      [(dtbpe)Ni(CH(2)CMe(3))][BAr(F)(4)] (6) with elimination of neopentane.

PMID- 20690600
TI  - Crystal structures and mutational analyses of acyl-CoA carboxylase beta subunit
      of Streptomyces coelicolor.
AB  - The first committed step of fatty acid and polyketides biosynthesis, the biotin
      dependent carboxylation of an acyl-CoA, is catalyzed by acyl-CoA carboxylases
      (ACCases) such as acetyl-CoA carboxylase (ACC) and propionyl-CoA carboxylase
      (PCC). ACC and PCC in Streptomyces coelicolor are homologue multisubunit
      complexes that can carboxylate different short chain acyl-CoAs. While ACC is able
      to carboxylate acetyl-, propionyl-, or butyryl-CoA with approximately the same
      specificity, PCC only recognizes propionyl- and butyryl-CoA as substrates. How
      ACC and PCC have such different specificities toward these substrates is only
      partially understood. To further understand the molecular basis of how the active
      site residues can modulate the substrate recognition, we mutated D422, N80, R456,
      and R457 of PccB, the catalytic beta subunit of PCC. The crystal structures of
      six PccB mutants and the wild type crystal structure were compared systematically
      to establish the sequence-structure-function relationship that correlates the
      observed substrate specificity toward acetyl-, propionyl-, and butyryl-CoA with
      active site geometry. The experimental data confirmed that D422 is a key
      determinant of substrate specificity, influencing not only the active site
      properties but further altering protein stability and causing long-range
      conformational changes. Mutations of N80, R456, and R457 lead to variations in
      the quaternary structure of the beta subunit and to a concomitant loss of enzyme
      activity, indicating the importance of these residues in maintaining the active
      protein conformation as well as a critical role in substrate binding.

PMID- 20690603
TI  - Determination of total sulfite in wine by ion chromatography after in-sample
      oxidation.
AB  - Sulfur dioxide (SO2) or sulfites are the most common preservatives used in
      winemaking. The level of total SO2 is subject to regulation. Currently, the
      regulatory determination of total SO2 (including sulfites) is done by the
      optimized Monier-Williams (OMW) method, which includes time-consuming
      distillation and titration steps. This paper describes the development and
      application of an alternative, rapid, straightforward, and reliable method for
      the determination of total sulfite in wine. In this method, a simple oxidation
      step using alkaline hydrogen peroxide (H2O2) solution is followed by ion
      chromatographic (IC) analysis of sulfate coupled with conductometric detection.
      Thirteen wines were analyzed in order to compare the in-sample oxidation method
      with the OMW-procedure. A t-test revealed satisfying compliance regarding sample
      preparation, i.e., alkaline H2O2 treatment and acidic distillation (OMW method).
      Comparable results were also obtained between IC analysis and acid/base
      titration. Our results indicate that the novel method (limit of quantification: 4
      mg SO2 L(-1)) is well suited for the cost-efficient monitoring of regulatory
      limits.

PMID- 20690604
TI  - Mapping the subcellular proteome of Shewanella oneidensis MR-1 using sarkosyl
      based fractionation and LC-MS/MS protein identification.
AB  - A simple and effective subcellular proteomic method for fractionation based on
      osmotic lysis, differential centrifugation, and Sarkosyl solubilization was
      applied to the Gram-negative bacterium Shewanella oneidensis to gain insight into
      its subcellular architecture. Global differences in bacterial cytoplasm, inner
      membrane, periplasm, and outer membrane protein fractions were observed by SDS
      PAGE and heme staining, and tryptic peptides were analyzed using high-resolution
      liquid chromatography-tandem mass spectrometry. Proteins predicted to be
      localized to each subcellular fraction were enriched approximately 2-fold (on
      average) in each fraction compared to crude cell lysates. In addition, the
      Sarkosyl solubilization method facilitated separation of the inner and outer
      membranes, making the procedure amenable for effective probing of the subcellular
      proteome of Gram-negative bacteria via liquid chromatography-tandem mass
      spectrometry. With 40% of the observable proteome represented, this study
      provides extensive information on both subcellular architecture and relative
      abundance of proteins in S. oneidensis and provides a foundation for future work
      on subcellular organization and protein-membrane interactions in other Gram
      negative bacteria.

PMID- 20690605
TI  - The N-glycome of human plasma.
AB  - N-linked glycans isolated from human plasma proteins have been profiled and
      sequenced by mass spectrometry using an ion trap instrument (ITMSn). The released
      glycans were prepared as reduced, methylated analogues and directly infused into
      a chip-based nanoelectrospray ionization system and analyzed by ITMSn. The
      resulting mass profiles (MS1) of IgG-depleted and nondepleted plasma samples were
      contrasted and these results were again compared with recent literature reports.
      Before depletion, approximately 50 independent glycan ions were detected; this
      more than doubled to 106 after depletion. The mass range profiled was 1-5 kDa
      which included many doubly and triply charged ions that were resolved by higher
      MS resolution. Selected ions in the depleted sample were disassembled to define
      their detailed structure providing a high-performance sequencing result. The
      simplicity of this nonchromatographic, direct infusion and gas-phase structural
      characterization compares most favorably with the latest reports using
      alternative instrumentation and adjunct techniques.

PMID- 20690606
TI  - Perfluorophenyl azides: new applications in surface functionalization and
      nanomaterial synthesis.
AB  - A major challenge in materials science is the ongoing search for coupling agents
      that are readily synthesized, capable of versatile chemistry, able to easily
      functionalize materials and surfaces, and efficient in covalently linking organic
      and inorganic entities. A decade ago, we began a research program investigating
      perfluorophenylazides (PFPA) as the coupling agents in surface functionalization
      and nanomaterial synthesis. The p-substituted PFPAs are attractive
      heterobifunctional coupling agents because of their two distinct and
      synthetically distinguishable reactive centers: (i) the fluorinated phenylazide,
      which is capable of forming stable covalent adducts, and (ii) the functional
      group R, which can be tailored through synthesis. Two approaches have been
      undertaken for material synthesis and surface functionalization. The first method
      involves synthesizing PFPA bearing the first molecule or material with a
      functional linker R and then attaching the resulting PFPA to the second material
      by activating the azido group. In the second approach, the material surface is
      first functionalized with PFPA via functional center R, and coupling of the
      second molecule or material is achieved with the surface azido groups. In this
      Account, we review the design and protocols of the two approaches, providing
      examples in which PFPA derivatives were successfully used in material surface
      functionalization, ligand conjugation, and the synthesis of hybrid nanomaterials.
      The methods developed have proved to be general and versatile, and they are
      applicable to a wide range of materials (especially those that lack reactive
      functional groups or are difficult to derivatize) and to various substrates of
      polymers, oxides, carbon materials, and metal films. The coupling chemistry can
      be initiated by light, heat, and electrons. Patterned structures can be generated
      by selectively activating the areas of interest. Furthermore, the process is easy
      to perform, and light activation occurs in minutes, greatly facilitating the
      efficiency of the reaction. PFPAs indeed demonstrate many benefits as versatile
      surface coupling agents and offer opportunities for further exploration.

PMID- 20690607
TI  - Surface-charge-dependent cell localization and cytotoxicity of cerium oxide
      nanoparticles.
AB  - Cerium oxide nanoparticles (nanoceria) have shown great potential as antioxidant
      and radioprotective agents for applications in cancer therapy. Recently, various
      polymer-coated nanoceria preparations have been developed to improve their
      aqueous solubility and allow for surface functionalization of these
      nanoparticles. However, the interaction of polymer-coated nanoceria with cells,
      their uptake mechanism, and subcellular localization are poorly understood.
      Herein, we engineered polymer-coated cerium oxide nanoparticles with different
      surface charges (positive, negative, and neutral) and studied their
      internalization and toxicity in normal and cancer cell lines. The results showed
      that nanoceria with a positive or neutral charge enters most of the cell lines
      studied, while nanoceria with a negative charge internalizes mostly in the cancer
      cell lines. Moreover, upon entry into the cells, nanoceria is localized to
      different cell compartments (e.g., cytoplasm and lysosomes) depending on the
      nanoparticle's surface charge. The internalization and subcellular localization
      of nanoceria plays a key role in the nanoparticles' cytotoxicity profile,
      exhibiting significant toxicity when they localize in the lysosomes of the cancer
      cells. In contrast, minimal toxicity is observed when they localize into the
      cytoplasm or do not enter the cells. Taken together, these results indicate that
      the differential surface-charge-dependent localization of nanoceria in normal and
      cancer cells plays a critical role in the nanoparticles' toxicity profile.

PMID- 20690608
TI  - Multi-source/component spray coating for polymer solar cells.
AB  - A multi-source/component spray coating process to fabricate the photoactive
      layers in polymer solar cells is demonstrated. Well-defined domains consisting of
      polymer:fullerene heterojunctions are constructed in ambient conditions using an
      alternating spray deposition method. This approach preserves the integrity of the
      layer morphology while forming an interpenetrating donor (D)/acceptor (A) network
      to facilitate charge transport. The formation of multi-component films without
      the prerequisite of a common solvent overcomes the limitations in conventional
      solution processes for polymer solar cells and enables us to process a wide
      spectrum of materials. Polymer solar cells based on poly(3-hexylthiophene):[6,6]
      phenyl C(61) butyric acid methyl ester spray-coated using this alternating
      deposition method deliver a power conversion efficiency of 2.8%, which is
      comparable to their blend solution counterparts. More importantly, this approach
      offers the versatility to independently select the optimal solvents for the donor
      and acceptor materials that will deliver well-ordered nanodomains. This method
      also allows the direct stacking of multiple photoactive polymers with
      controllable absorption in a tandem structure even without an interconnecting
      junction layer. The introduction of multiple photoactive materials through
      multisource/component spray coating offers structural flexibility and tenability
      of the photoresponse for future polymer solar cell applications.

PMID- 20690609
TI  - Dielectrophoretic trapping and polarizability of DNA: the role of spatial
      conformation.
AB  - Dielectrophoresis is a convenient tool for controlled manipulation of DNA with
      numerous applications, including DNA trapping, stretching, and separation.
      However, the mechanisms behind the dielectrophoretic properties of DNA are still
      under debate, and the role of conformation has not been addressed yet. Here, we
      quantify dielectrophoretic effects on DNA by determining its polarizability from
      microfluidic single molecule trapping experiments. We systematically study
      different DNA configurations (linear and supercoiled, 6-164 kbp) and demonstrate
      that the polarizability strongly depends on the specific conformation and size of
      the DNA molecules. The connection to its spatial extension is established by
      measuring diffusion coefficients and from that the radii of gyration; details
      about the spatial DNA structure are obtained from atomic force microscopy images.
      For linear and supercoiled DNA fragments, we found a power-law scaling for the
      polarizabilities and the diffusion coefficients. Our results imply a scaling of
      the polarizability with the radius of gyration, alpha approximately Rg0.9+/-0.1
      and alpha approximately Rg1.6+/-0.2 for linear and supercoiled DNA, respectively.
      As an application, we demonstrate the separation of DNA topoisomers based on
      their dielectrophoretic properties, achieving baseline resolution within 210 s.
      Purified DNA samples of specific configuration may be of great importance for DNA
      nanoassembly or future DNA vaccines.

PMID- 20690610
TI  - Development of mass spectrometry based techniques for the identification and
      determination of compositional variability in recombinant polyclonal antibody
      products.
AB  - Recombinant polyclonal antibodies are a new class of protein biologics, combining
      a defined number of target-specific antibodies, developed for therapeutic use
      across various indications. Development, manufacture, and release of recombinant
      polyclonal antibodies as well characterized biological products have required
      development of new chemistry, manufacturing, and control (CMC) technologies.
      Sym001 is a recombinant polyclonal antibody product containing 25 unique
      antibodies specific for the Rhesus D antigen. Sym001 drug substance is
      manufactured using a single batch technology, Sympress. Here, we describe the
      development of two novel mass spectrometry based methods that allows
      identification of individual antibodies in the Sym001 drug substance, through the
      determination of unique marker peptides or antibody light chains. The two methods
      provide an unambiguous identification of the 25 unique antibodies comprised in
      the Sym001 drug substance. Furthermore, the light chain liquid chromatography
      mass spectrometry (LC-MS) method has been developed to allow the determination of
      the relative distribution of the 25 antibodies. The light chain LC-MS method has
      demonstrated linearity, specificity, precision, and accuracy, thus qualifying it
      for use in the quality control of recombinant polyclonal antibodies for human
      use. The development of such quantitative methods is central for the development
      and quality control of additional therapeutic recombinant polyclonal antibody
      products.

PMID- 20690611
TI  - Synthesis of L-altro-1-deoxynojirimycin, D-allo-1-deoxynojirimycin, and D-galacto
      1-deoxynojirimycin from a single chiral cyanohydrin.
AB  - The chemoenzymatic synthesis of three 1-deoxynojirimycin-type iminosugars is
      reported. Key steps in the synthetic scheme include a Dibal reduction
      transimination-sodium borohydride reduction cascade of reactions on an
      enantiomerically pure cyanohydrin, itself prepared employing almond
      hydroxynitrile lyase (paHNL) as the common precursor. Ensuing ring-closing
      metathesis and Upjohn dihydroxylation afford the target compounds.

PMID- 20690612
TI  - Squaramide-based reagent for selective chromogenic sensing of Cu(II) through a
      zwitterion radical.
AB  - A minimalist squaramide-based chemodosimeter for Cu(2+) is described. Upon
      selective chelation to 2, Cu(2+) induces the formation of a highly colored
      zwitterionic radical, which is kinetically stable for hours. The presence of a
      radical is confirmed by EPR and ESI-MS. It is then possible to use reagent 2 for
      visual and selective sensing of Cu(2+) at neutral pH.

PMID- 20690613
TI  - Palhinine A, a novel alkaloid from Palhinhaea cernua.
AB  - Palhinine A, a novel C(16)N-type Lycopodium alkaloid with a unique 5/6/6/9
      tetracyclic ring system, was isolated from the whole plant of Palhinhaea cernua
      L. (Lycopodiaceae). Its structure was elucidated by spectroscopic methods, and
      the absolute configuration was determined by single-crystal X-ray diffraction
      analysis using the Flack parameter. Palhinine A is reported as the first example
      of Lycopodium alkaloids of which C-16 is fused to a new ring through a C-16-C-4
      lingkage.

PMID- 20690614
TI  - Directing the morphology and differentiation of skeletal muscle cells using
      oriented cellulose nanowhiskers.
AB  - Radially oriented submonolayer surfaces of 10-15 nm diameter cellulose
      nanowhiskers (CNWs) were prepared by spin-coating. The response of myoblasts
      (muscle cells) to the surfaces was assessed using atomic force microscopy (AFM),
      immunocytochemistry, and image analysis. Despite the small size of the CNWs, the
      myoblasts oriented along the CNW surfaces. Upon differentiation, the myoblasts
      produced striking radial patterns of myotubes, following the radial pattern of
      the CNWs. This facile method of nanopatterning surfaces may be applied where the
      directed growth of tissue is required and shows for the first time the potential
      of CNWs for tissue engineering applications.

PMID- 20690615
TI  - Functional mimics of glutathione peroxidase: bioinspired synthetic antioxidants.
AB  - Oxidative stress is caused by an imbalance between the production of reactive
      oxygen species (ROS) and the biological system's ability to detoxify these
      reactive intermediates. Mammalian cells have elaborate antioxidant defense
      mechanisms to control the damaging effects of ROS. Glutathione peroxidase (GPx),
      a selenoenzyme, plays a key role in protecting the organism from oxidative damage
      by catalyzing the reduction of harmful hydroperoxides with thiol cofactors. The
      selenocysteine residue at the active site forms a "catalytic triad" with
      tryptophan and glutamine, which activates the selenium moiety for an efficient
      reduction of peroxides. After the discovery that ebselen, a synthetic
      organoselenium compound, mimics the catalytic activity of GPx both in vitro and
      in vivo, several research groups developed a number of small-molecule selenium
      compounds as functional mimics of GPx, either by modifying the basic structure of
      ebselen or by incorporating some structural features of the native enzyme. The
      synthetic mimics reported in the literature can be classified in three major
      categories: (i) cyclic selenenyl amides having a Se-N bond, (ii) diaryl
      diselenides, and (iii) aromatic or aliphatic monoselenides. Recent studies show
      that ebselen exhibits very poor GPx activity when aryl or benzylic thiols such as
      PhSH or BnSH are used as cosubstrates. Because the catalytic activity of each GPx
      mimic largely depends on the thiol cosubstrates used, the difference in the
      thiols causes the discrepancies observed in different studies. In this Account,
      we demonstrate the effect of amide and amine substituents on the GPx activity of
      various organoselenium compounds. The existence of strong Se...O/N interactions
      in the selenenyl sulfide intermediates significantly reduces the GPx activity.
      These interactions facilitate an attack of thiol at selenium rather than at
      sulfur, leading to thiol exchange reactions that hamper the formation of
      catalytically active selenol. Therefore, any substituent capable of enhancing the
      nucleophilic attack of thiol at sulfur in the selenenyl sulfide state would
      enhance the antioxidant potency of organoselenium compounds. Interestingly,
      replacement of the sec-amide substituent by a tert-amide group leads to a
      weakening of Se...O interactions in the selenenyl sulfide intermediates. This
      modification results in 10- to 20-fold enhancements in the catalytic activities.
      Another strategy involving the replacement of tert-amide moieties by tert-amino
      substituents further increases the activity by 3- to 4-fold. The most effective
      modification so far in benzylamine-based GPx mimics appears to be either the
      replacement of a tert-amino substituent by a sec-amino group or the introduction
      of an additional 6-methoxy group in the phenyl ring. These strategies can
      contribute to a remarkable enhancement in the GPx activity. In addition to
      enhancing catalytic activity, a change in the substituents near the selenium
      moiety alters the catalytic mechanisms. The mechanistic investigations of
      functional mimics are useful not only for understanding the complex chemistry at
      the active site of GPx but also for designing and synthesizing novel antioxidants
      and anti-inflammatory agents.

PMID- 20690616
TI  - Polyhistidine peptide inhibitor of the Abeta calcium channel potently blocks the
      Abeta-induced calcium response in cells. Theoretical modeling suggests a
      cooperative binding process.
AB  - On the basis of the consistent demonstrations that the Abeta peptide of
      Alzheimer's disease forms calcium permeant channels in artificial membranes, we
      have proposed that the intracellular calcium increase observed in cells exposed
      to Abeta is initiated by calcium fluxes through Abeta channels. We have found
      that a small four-histidine peptide, NAHis04, potently inhibits the Abeta-induced
      calcium channel currents in artificial lipid membranes. Here we report that
      NaHis04 also potently blocks the intracellular calcium increase which is observed
      in cells exposed to Abeta. PC12 cells loaded with Fura-2AM show a rapid increase
      in fluorescence and a rapid return to baseline after Abeta is added to the
      medium. This fluorescence change occurs even when the medium contains
      nitrendipine, a voltage-gated calcium channel blocker, but fails to occur when
      application of Abeta is preceded by addition of NAHis04. Steep dose-response
      curves of the percentage of responding cells and cell viability show that NAHis04
      inhibits in the micromolar range in an apparently cooperative manner. We have
      developed numerous models of Abeta pores in which the first part of the Abeta
      sequence forms a large beta-barrel ending at His 13. We have modeled how up to
      four NAHis04 peptides may block these types of pores by binding to side chains of
      Abeta residues Glu 11, His 13, and His 14.

PMID- 20690617
TI  - Ion-selective permeability of an ultrathin nanoporous silicon membrane as probed
      by scanning electrochemical microscopy using micropipet-supported ITIES tips.
AB  - We report on the application of scanning electrochemical microscopy (SECM) to the
      measurement of the ion-selective permeability of porous nanocrystalline silicon
      membrane as a new type of nanoporous material with potential applications in
      analytical, biomedical, and biotechnology device development. The reliable
      measurement of high permeability in the molecularly thin nanoporous membrane to
      various ions is important for greater understanding of its structure-permeability
      relationship and also for its successful applications. In this work, this
      challenging measurement is enabled by introducing two novel features into
      amperometric SECM tips based on the micropipet-supported interface between two
      immiscible electrolyte solutions (ITIES) to reveal the important ion-transport
      properties of the ultrathin nanopore membrane. The tip of a conventional heat
      pulled micropipet is milled using the focused ion beam (FIB) technique to be
      smoother, better aligned, and subsequently, approach closer to the membrane
      surface, which allows for more precise and accurate permeability measurement. The
      high membrane permeability to small monovalent ions is determined using FIB
      milled micropipet tips to establish a theoretical formula for the membrane
      permeability that is controlled by free ion diffusion across water-filled
      nanopores. Moreover, the ITIES tips are rendered selective for larger polyions
      with biomedical importance, i.e., polyanionic pentasaccharide Arixtra and
      polycationic peptide protamine, to yield the membrane permeability that is lower
      than the corresponding diffusion-limited permeability. The hindered transport of
      the respective polyions is unequivocally ascribed to electrostatic and steric
      repulsions from the wall of the nanopores, i.e., the charge and size effects.

PMID- 20690618
TI  - Metal-free regioselective oxidative biaryl coupling leading to head-to-tail
      bithiophenes: reactivity switching, a concept based on the iodonium(III)
      intermediate.
AB  - A new synthetic concept for obtaining unsymmetrical biaryl coupling products by
      an oxidative method is reported. Our synthetic strategy casts light on the
      reaction intermediate for switching the reactivity of 3-substituted thiophenes.
      On the basis of this strategy, a novel direct method for the synthesis of head-to
      tail bithiophenes using hypervalent iodine(III) reagents has been developed.

PMID- 20690619
TI  - Structural and biochemical characterization of the cytochrome P450 CypX
      (CYP134A1) from Bacillus subtilis: a cyclo-L-leucyl-L-leucyl dipeptide oxidase.
AB  - Cytochrome P450 CypX (CYP134A1), isolated from Bacillus subtilis, has previously
      been implicated in the three-step oxidative transformation of the
      diketopiperazine cyclo-l-leucyl-l-leucyl into pulcherriminic acid, a precursor of
      the extracellular iron chelate pulcherrimin. In this study, we present the first
      experimental data relating to CYP134A1, where we show that CYP134A1 binds cyclo-l
      leucyl-l-leucyl with an affinity of 24.5 +/- 0.5 muM. Structurally related
      diketopiperazines sharing similar alkyl side chains to cyclo-l-leucyl-l-leucyl
      also bind to CYP134A1 with comparable affinity. CYP134A1 is capable of catalyzing
      the in vitro oxidation of diketopiperazine substrates when supported with several
      alternate electron transfer partner systems. Products containing one additional
      oxygen atom and which are intermediate products of the expected pulcherriminic
      acid were identified by GCMS. The oxidation of related diketopiperazines reveals
      that different oxidative pathways exist for CYP134A1-catalyzed diketopiperazine
      oxidation. The crystal structure of CYP134A1 has been determined to 2.7 A
      resolution in the absence of substrate and in the presence of bound
      phenylimidazole ligands to 3.1 and 3.2 A resolution. The active site is dominated
      by hydrophobic residues and contains an unusual proline residue in place of the
      normally conserved alcohol residue that typically plays an important role in
      oxygen activation. The B-B(2) substrate recognition loop, which forms part of the
      active site, shows considerable flexibility and was found in both open and closed
      conformations in different structures. These results represent the first insights
      into the structural and biochemical basis underlying the multistep oxidation
      catalyzed by CYP134A1.

PMID- 20690620
TI  - Mechanistic and stereochemical studies of glycine oxidase from Bacillus subtilis
      strain R5.
AB  - Glycine oxidase gene from a strain of Bacillus subtilis was cloned and expressed
      in Escherichia coli. The purified enzyme was found, by mass spectrometry, to have
      a protein M(r) of 40763 (value of 40761.6 predicted from DNA sequence) and a FAD
      prosthetic group M(r) of 785.1 (theoretical value of 785.5). Glycine oxidase
      optimally catalyzes the conversion of glycine and oxygen into glyoxylate,
      hydrogen peroxide, and ammonia. Using samples of [2-RS-(3)H(2),2-(14)C]-, [2-R
      (3)H,2-(14)C]-, and [2-S-(3)H,2-(14)C]glycine, we found that in the overall
      process H(Si) is removed. Incubation of the enzyme with [2-RS-(3)H(2),2
      (14)C]glycine under anaerobic conditions, when only the reducing half of the
      reaction can occur, led to the recovery of 98.5% of the original glycine, which
      had the same (3)H:(14)C ratio as the starting substrate. The primary isotope
      effect was studied using [2-(2)H(2)]glycine, and we found that the specificity
      constants, k(cat)/K(M), for the protio and deuterio substrates were 1.46 x 10(3)
      and 1.05 x 10(2) M(-1) s(-1), respectively. Two alternative mechanisms for FAD
      containing oxidases that involve either the intermediacy of a FADH(2)-imino acid
      complex or an amino acid covalently linked to FAD, formed via a carbanion, have
      been considered. The current knowledge of the mechanisms is reviewed, and we
      argue that a mechanism involving the FADH(2)-imino acid complex can be dissected
      to satisfactorily explain some of puzzling observations for which the carbanion
      mechanism was originally conceived. Furthermore, our results, together with
      observations in the literature, suggest that the interaction of glycine with the
      enzyme occurs within a tight ternary complex, which is protected from the protons
      of the medium.

PMID- 20690621
TI  - Noncovalent interactions in the gas-phase conformers of anionic iduronate (methyl
      2-o-sulfo-alpha-L-iduronate): variation of subconformer versus ring conformer
      energetics for a prototypical anionic monosaccharide studied using computational
      methods.
AB  - The conformational preferences of the prototypical anionic monosaccharide (methyl
      2-O-sulfo-alpha-L-iduronate) have been studied at various computational levels to
      investigate the energetic variation of 17 subconformers associated with the
      (4)C(1), (2)S(0), (5)S(1), and (1)C(4) ring conformers. These calculations
      include the first fully optimized MP2 calculations that have been performed for
      an anionic sugar system, and therefore allow an assessment of the performance of
      a group of DFT functionals (B3LYP, PW91PW91, and M05-2X) for treating the
      noncovalent dispersion and anomeric effects that are present in this system. We
      find that the recently developed M05-2X functional of Truhlar and co-workers [Y.
      Zhao, N. E. Schultz, D. G. Truhlar, J. Chem. Theory Comput., 2006, 2, 364]
      reproduces the MP2 results most closely, thus indicating that it may well be
      suitable for computational studies of larger ionic saccharides. Most importantly,
      the results presented indicate that it is crucial to consider the subconformers
      (which correspond to rearrangements of the sugar-ring side-chains) of the main
      ring-conformers in order to obtain a reliable overview of the potential energy
      surface of such systems. We find that the lowest isolated (gas-phase) conformer
      corresponds to a (4)C(1) chair conformer, which displays a pair of strong C(3)
      OH...SO(3)(-) and OMe...SO(3)(-) electrostatic hydrogen-bonding interactions,
      coupled with a looser C(4)-OH...SO(3)(-) interaction. Overall, the relative
      energies of the subconformers appear to be straightforwardly related to the
      number of hydrogen-bonding interactions that each conformer displays among its
      pendant functional groups.

PMID- 20690622
TI  - Band gap opening of bilayer graphene by F4-TCNQ molecular doping and externally
      applied electric field.
AB  - The band gap opening of bilayer graphene with one side surface adsorption of F4
      TCNQ is reported. F4-TCNQ doped bilayer graphene shows p-type semiconductor
      characteristics. With a F4-TCNQ concentration of 1.3 x 10(-10) mol/cm(2), the
      charge transfer between each F4-TCNQ molecule and graphene is 0.45e, and the
      built-in electric field, E(bi), between the graphene layers could reach 0.070
      V/A. The charge transfer and band gap opening of the F4-TCNQ-doped graphene can
      be further modulated by an externally applied electric field (E(ext)). At 0.077
      V/A, the gap opening at the Dirac point (K), DeltaE(K) = 306 meV, and the band
      gap, E(g) = 253 meV, are around 71% and 49% larger than those of the pristine
      bilayer under the same E(ext).

PMID- 20690623
TI  - Charge transfer state versus hot exciton dissociation in polymer-fullerene
      blended solar cells.
AB  - We examine the significance of hot exciton dissociation in two archetypical
      polymer-fullerene blend solar cells. Rather than evolving through a bound charge
      transfer state, hot processes are proposed to convert excitons directly into free
      charges. But we find that the internal quantum yields of carrier photogeneration
      are similar for both excitons and direct excitation of charge transfer states.
      The internal quantum yield, together with the temperature dependence of the
      current-voltage characteristics, is consistent with negligible impact from hot
      exciton dissociation.

PMID- 20690624
TI  - Identification of CKD-516: a potent tubulin polymerization inhibitor with marked
      antitumor activity against murine and human solid tumors.
AB  - Tubulin polymerization inhibitors had emerged as one of promising anticancer
      therapeutics because of their dual mechanism of action, i.e. apoptosis by cell
      cycle arrest and VDA, vascular disrupting agent. VDAs are believed to be more
      efficient, less toxic, and several of them are currently undergoing clinical
      trials. To identify novel tubulin inhibitors that possess potent cytotoxicity and
      strong inhibition of tubulin polymerization as well as potent in vivo antitumor
      efficacy, we have utilized benzophenone scaffold. Complete SAR analysis of newly
      synthesized analogues that were prepared by incorporation of small heterocycles
      (C2, C4, and C5 position) into B-ring along with the evaluation of their in vitro
      cytotoxicity, tubulin polymerization inhibition, and in vivo antitumor activity
      allowed us to identify 22 (S516). Compound 22 was found to have potent
      cytotoxicity against several cancer cells including P-gp overexpressing MDR
      positive cell line (HCT15). It also induced cell cycle arrest at G(2)/M phase,
      which is associated with strong inhibition of tubulin polymerization. Its in vivo
      efficacy was improved by preparing its (l)-valine prodrug, 65 (CKD-516), which
      together with greatly improved aqueous solubility has shown marked antitumor
      efficacy against both murine tumors (CT26 and 3LL) and human xenogratfs (HCT116
      and HCT15) in mice.

PMID- 20690625
TI  - Electron momentum spectroscopy of norbornadiene at the benchmark ADC(3) level.
AB  - An extensive study, throughout the valence region, of the electronic structure,
      ionization spectrum, and electron momentum distributions of norbornadiene is
      presented, on the ground of accurate calculations of valence one-electron and
      shake-up ionization energies and of the related Dyson orbitals, using one
      particle Green's function (1p-GF) theory in conjunction with the so-called third
      order algebraic diagrammatic construction scheme [ADC(3)]. Comparison is made
      with results obtained from standard (B3LYP) Kohn-Sham orbitals and measurements
      employing electron momentum spectroscopy, taking into account the contamination
      of inner- and outer-valence spectral bands by numerous shake-up states. Four
      relatively intense shake-up lines at 12.1, 16.4, 17.6, and 17.8 eV are found to
      yield recognizable spectral fingerprints in the EMS experiments. Valence bands at
      electron binding energies larger than 20 eV are subject to a complete breakdown
      of the orbital picture of ionization.

PMID- 20690626
TI  - Bimetallic nickel aluminum mediated para-selective alkenylation of pyridine:
      direct observation of eta2,eta1-pyridine Ni(0)-Al(III) intermediates prior to C-H
      bond activation.
AB  - We have presented new amino-NHC Ni-Al complex mediated para C-H bond activation
      for pyridine and quinolin, and isolated for the first time the intermediate
      structure of a bimetallic eta(2),eta(1)-pyridine nickel aluminum complex prior to
      its C-H activation, which serves as key evidence for bimetallic catalysis.

PMID- 20690627
TI  - FLAP: GRID molecular interaction fields in virtual screening. validation using
      the DUD data set.
AB  - The performance of FLAP (Fingerprints for Ligands and Proteins) in virtual
      screening is assessed using a subset of the DUD (Directory of Useful Decoys)
      benchmarking data set containing 13 targets each with more than 15 different
      chemotype classes. A variety of ligand and receptor-based virtual screening
      approaches are examined, using combinations of individual templates 2D structures
      of known actives, a cocrystallized ligand, a receptor structure, or a
      cocrystallized ligand-biased receptor structure. We examine several data fusion
      approaches to combine the results of the individual virtual screens. In doing so,
      we show that excellent chemotype enrichment is achieved in both single target
      ligand-based and receptor-based approaches, of approximately 17-fold over random
      on average at a false positive rate of 1%. We also show that using as much
      starting knowledge as possible improves chemotype enrichment, and that data
      fusion using Pareto ranking is an effective method to do this giving up to 50%
      improvement in enrichment over the single methods. Finally we show that if
      inactivity or decoy data is incorporated, automatically training the scoring
      function in FLAP improves recovery still further, with almost 2-fold improvement
      over the enrichments shown by the single methods. The results clearly demonstrate
      the utility of FLAP for virtual screening when either a limited or wide range of
      prior knowledge is available.

PMID- 20690628
TI  - Structures and heats of formation of simple alkaline earth metal compounds:
      fluorides, chlorides, oxides, and hydroxides for Be, Mg, and Ca.
AB  - Geometry parameters, frequencies, heats of formation, and bond dissociation
      energies are predicted for the simple alkaline earth (Be, Mg and Ca) fluorides,
      chlorides, oxides, and hydroxides at the coupled cluster theory [CCSD(T)] level
      including core-valence correlation with the aug-cc-pwCVnZ basis sets up to n = 5
      in some cases. Additional corrections (scalar relativistic effects, vibrational
      zero-point energies, and atomic spin-orbit effects) were necessary to accurately
      calculate the total atomization energies and heats of formation. The calculated
      geometry parameters, frequencies, heats of formation, and bond dissociation
      energies are compared with the available experimental data. For a number of these
      alkaline earth compounds, the experimental geometries and energies are not
      reliable. MgF(2) and BeF(2) are predicted to be linear and CaF(2) is predicted to
      be bent. BeOH is predicted to be bent, whereas MgOH and CaOH are linear. The OBeO
      angle in Be(OH)(2) is not linear, and the molecule has C(2) symmetry. The heat of
      formation at 298 K for MgO is calculated to be 32.3 kcal/mol, and the bond
      dissociation energy at 0 K is predicted to be 61.5 kcal/mol.

PMID- 20690629
TI  - Vibrational energy flow controls internal conversion in a transition metal
      complex.
AB  - Internal conversion (IC) between excited electronic states is a fundamental
      photophysical process that is important for understanding protection from UV
      radiation, energy transfer pathways and electron injection in artificial
      photosynthetic systems and organic solar cells. We have studied IC between three
      singlet MLCT states in an iridium complex using femtosecond fluorescence
      spectroscopy. Very fast IC with a time constant of <20 fs is observed from the
      highest state and a much slower relaxation to the lowest energy singlet state on
      a 70 fs time scale. The abrupt slowdown of the relaxation rate occurs when there
      is >0.6 eV of vibrational energy stored in the complex that has to be dissipated
      by intramolecular vibrational redistribution before further IC to the lower
      energy states can occur. These results show that the ability to dissipate
      vibrational energy can control the relaxation process in this class of materials.

PMID- 20690630
TI  - Kinetic analysis of 14-3-3-inhibited Arabidopsis thaliana nitrate reductase.
AB  - Eukaryotic assimilatory nitrate reductase (NR) is a dimeric multidomain molybdo
      heme-flavo protein that catalyzes the first and rate-limiting step in the nitrate
      assimilation of plants, algae, and fungi. Nitrate reduction takes place at the N
      terminal molybdenum cofactor-containing domain. Reducing equivalents are derived
      from NADH, which reduce the C-terminal FAD domain followed by single-electron
      transfer steps via the middle heme domain to the molybdenum center. In plants,
      nitrate reduction is post-translationally inhibited by phosphorylation and
      subsequent binding of 14-3-3 protein to a conserved phosphoserine located in the
      surface-exposed hinge between the catalytic and heme domain. Here we investigated
      Arabidopsis thaliana NR activity upon phosphorylation and 14-3-3 binding by using
      a fully defined in vitro system with purified proteins. We demonstrate that among
      different calcium-dependent protein kinases (CPKs), CPK-17 efficiently
      phosphorylates Ser534 in NR. Out of eight purified Arabidopsis 14-3-3 proteins,
      isoforms omega, kappa, and lambda exhibited the strongest inhibition of NR. The
      kinetic parameters of noninhibited, phosphorylated NR (pNR) and pNR in a complex
      with 14-3-3 were investigated. An 18-fold reduction in k(cat) and a decrease in
      the apparent K(M)(nitrate) (from 280 to 141 MUM) were observed upon binding of 14
      3-3 to pNR, suggesting a noncompetitive inhibition with a preferential binding to
      the substrate-bound state of the enzyme. Recording partial activities of NR
      demonstrated that the transfer of electrons to the heme is not affected by 14-3-3
      binding. The Ser534Ala variant of NR was not inhibited by 14-3-3 proteins. We
      propose that 14-3-3 binding to Ser534 blocks the transfer of electrons from heme
      to nitrate by arresting the domain movement via hinge 1.

PMID- 20690631
TI  - Supramolecular assemblies in ionic liquid catalysis for aza-Michael reaction.
AB  - Supramolecular assemblies formed by a relay of cooperative hydrogen bonds and
      charge-charge interactions have been identified/characterized by (+ve) ESI and
      MALDI-TOF-TOF MS and MS-MS studies during the aza-Michael reaction of amines with
      alpha,beta-unsaturated carbonyl compounds in the presence of ionic liquids (ILs)
      digging out the role of catalysis by ILs, forming the basis of rational
      design/selection as organocatalysts, and offering a diagnostic model to
      predict/rationalize the selectivity of the aza-Michael reaction in a competitive
      environment.

PMID- 20690633
TI  - Infrared spectra of CF(2)=CHD and CF(2)=CD(2): scaled quantum-chemical force
      fields and an equilibrium structure for 1,1-difluoroethylene.
AB  - Infrared (IR) spectra in the gas phase are reported for CF(2)=CHD and CF(2)=CD(2)
      in the region 350-4000 cm(-1). Ab initio calculations of an harmonic force-field
      and anharmonicity constants have been made with an MP2/aug-cc-pVTZ model. These
      enable a number of Fermi resonances in each species to be analyzed and a complete
      set of "observed" harmonic frequencies to be derived. The latter are combined
      with similar data for CF(2)=CH(2) in a scaling of the model harmonic force field
      to both anharmonic and harmonic frequencies. Inspection of the scale factors
      reveals minor defects of the model, evident in the out-of-plane wagging modes and
      in the CF stretch/CF stretch interaction force constant. Fermi resonance
      treatments involved in all isotopomers studied are compatible with the overall
      force-field refinement results. The treatment leaves a small anomaly in the (13)C
      shift on nu(1). Improved microwave spectra are reported for five isotopic
      species, and a semiexperimental equilibrium structure for F(2)C=CH(2) is
      determined and compared favorably with the structure obtained from new high-level
      ab initio calculations. Centrifugal distortion constants are predicted for the
      five isotopic species, and those for F(2)C=CH(2) are compared with values fit to
      microwave spectra.

PMID- 20690632
TI  - Fluostatins produced by the heterologous expression of a TAR reassembled
      environmental DNA derived type II PKS gene cluster.
AB  - Culture independent approaches for accessing small molecules produced by
      uncultured bacteria are often hampered by the inability to easily clone
      environmental DNA (eDNA) fragments large enough to capture intact biosynthetic
      gene clusters that can be used in heterologous expression studies. Here we show
      that homology screening of eDNA megalibraries for clones containing natural
      product biosynthetic genes, coupled with transformation-assisted recombination
      (TAR) in yeast, can be used to access large, functionally intact, natural product
      gene clusters from the environment. The eDNA derived gene cluster reported here
      was functionally reconstructed from two overlapping cosmid clones using TAR. The
      isolation and structure elucidation of three new fluostatins (F, G, and H)
      produced by this TAR reconstructed gene cluster is described.

PMID- 20690634
TI  - Influence of gelatin cues in PCL electrospun membranes on nerve outgrowth.
AB  - The design of functionalized polymers that can elicit specific biological
      responses and the development of methods to fabricate new devices that
      incorporate biological cues are of great interest to the biomedical community.
      The realization of nanostructured matrices that exhibit biological properties and
      that comprise fibers with diameters of similar scale to those of the natural
      extracellular matrix (ECM) would enable the provision of tailored materials for
      tissue engineering. Accordingly, the goal of this work is to create a
      biologically active functionalized electrospun matrix capable of guiding neurite
      growth for the regeneration of nerve tissue. In this study, nanoscale electrospun
      membranes made of poly epsilon-caprolactone enhanced with gelatin from calf skin
      were investigated to validate their biological response under in vitro culture of
      PC-12 nerve cells. Preliminary observations from SEM studies supported by image
      analysis highlighted the nanoscale texture of the scaffold with fiber diameters
      equal to 0.548 +/- 0.140 MUm. In addition, contact angle measurements confirmed
      the hydrophilic behavior of the membranes, ascribable to the gelatin content. We
      demonstrate that the balance of morphological and biochemical properties improves
      all the fundamental biological events of nerve regeneration, enhancing cell
      adhesion, proliferation, and differentiation in comparison with PCL nanofibrous
      scaffolds, as well as supporting the neurite outgrowth.

PMID- 20690635
TI  - Discovery of canagliflozin, a novel C-glucoside with thiophene ring, as sodium
      dependent glucose cotransporter 2 inhibitor for the treatment of type 2 diabetes
      mellitus.
AB  - We discovered that C-glucosides 4 bearing a heteroaromatic ring formed
      metabolically more stable inhibitors for sodium-dependent glucose cotransporter 2
      (SGLT2) than the O-glucoside, 2 (T-1095). A novel thiophene derivative 4b-3
      (canagliflozin) was a highly potent and selective SGLT2 inhibitor and showed
      pronounced anti-hyperglycemic effects in high-fat diet fed KK (HF-KK) mice.

PMID- 20690636
TI  - Recombinant expression, in vitro refolding, and biophysical characterization of
      the human glucagon-like peptide-1 receptor.
AB  - Activation of the glucagon-like peptide-1 receptor (GLP-1R) upon ligand binding
      leads to the release of insulin from pancreatic cells. This strictly glucose
      dependent process renders the receptor and its ligands useful in the treatment of
      type II diabetes mellitus. To enable a biophysical characterization in vitro, we
      expressed the human full-length GLP-1R in the cytosol of Escherichia coli as
      inclusion bodies. After purification, refolding of the SDS-solubilized receptor
      was achieved by the exchange of SDS against the detergent Brij78 using an
      artificial chaperone system. Far-UV circular dichroism spectroscopic studies
      revealed that the receptor adopts a characteristic alpha-helical structure in
      Brij78 micelles. Ligand binding of the renatured protein was quantified by
      fluorescence quenching and surface plasmon resonance spectroscopy. In the
      presence of Brij micelles, the refolded receptor binds the agonist exendin-4 with
      an apparent dissociation constant of approximately 100 nM in a reversible one
      step mechanism. To demonstrate that the detected ligand binding activity is not
      only due to an autonomously functional N-terminal domain (nGLP-1R) but also due
      to additional contacts with the juxtamembrane part, we separately expressed and
      refolded the extracellular domain relying on identical protocols established for
      the full-length GLP-1R. In support of the suggested multidomain binding mode, the
      nGLP-1R binds exendin-4 with a lower affinity (K(app) in the micromolar range)
      and a different kinetic mechanism. The lower ligand affinity of the nGLP-1R
      results entirely from a decreased kinetic stability of the receptor-ligand
      complex, dissociation of which is approximately 40-fold faster in the case of the
      nGLP-1R compared to the full-length GLP-1R. In summary, a framework was developed
      to produce functional human full-length GLP-1R by recombinant expression in E.
      coli as a prerequisite for eventual structure determination and a rigorous
      biophysical characterization including protein variants.

PMID- 20690637
TI  - Engineering the enolase magnesium II binding site: implications for its
      evolution.
AB  - The glycolytic enzyme enolase catalyzes the reversible elimination of water from
      2-phosphoglycerate (2-PGA) to form phosphoenolpyruvate (PEP). Two magnesium ions
      in the active site are thought to facilitate the reaction by activation of the C2
      proton of 2-PGA and charge stabilization of the intermediate. The initial
      abstraction of a proton from a carboxylic acid is common to all members of the
      enolase superfamily, yet in all other known members of this superfamily, only one
      magnesium ion (MgI) per active site is sufficient to promote catalysis. We wanted
      to further investigate the importance of the second magnesium ion (MgII) for the
      catalytic mechanism of yeast enolase 1. Toward this end, we removed all MgII
      coordinating residues and replaced substrate-MgII interactions by introducing
      positively charged side chains. High-resolution crystal structures and activity
      assays show that the introduced positively charged side chains effectively
      prohibit MgII binding but fail to promote catalysis. We conclude that enolase is
      inactive without MgII, yet control mutants without additional positively charged
      side chains retain basal enolase activity through binding of magnesium to 2-PGA
      in an open active site without the help of MgII coordinating residues. Thus, we
      believe that ancestral enolase activity might have evolved in a member of the
      enolase superfamily that provides only the necessary catalytic residues and the
      binding site for MgI. Additionally, precatalytic binding of 2-PGA to the apo
      state of enolase was observed.

PMID- 20690638
TI  - Construction of confidence regions for isotopic abundance patterns in LC/MS data
      sets for rigorous determination of molecular formulas.
AB  - It has long been recognized that estimates of isotopic abundance patterns may be
      instrumental in identifying the many unknown compounds encountered when
      conducting untargeted metabolic profiling using liquid chromatography/mass
      spectrometry. While numerous methods have been developed for assigning heuristic
      scores to rank the degree of fit of the observed abundance patterns with
      theoretical ones, little work has been done to quantify the errors that are
      associated with the measurements made. Thus, it is generally not possible to
      determine, in a statistically meaningful manner, whether a given chemical formula
      would likely be capable of producing the observed data. In this paper, we present
      a method for constructing confidence regions for the isotopic abundance patterns
      based on the fundamental distribution of the ion arrivals. Moreover, we develop a
      method for doing so that makes use of the information pooled together from the
      measurements obtained across an entire chromatographic peak, as well as from any
      adducts, dimers, and fragments observed in the mass spectra. This greatly
      increases the statistical power, thus enabling the analyst to rule out a
      potentially much larger number of candidate formulas while explicitly guarding
      against false positives. In practice, small departures from the model assumptions
      are possible due to detector saturation and interferences between adjacent
      isotopologues. While these factors form impediments to statistical rigor, they
      can to a large extent be overcome by restricting the analysis to moderate ion
      counts and by applying robust statistical methods. Using real metabolic data, we
      demonstrate that the method is capable of reducing the number of candidate
      formulas by a substantial amount, even when no bromine or chlorine atoms are
      present. We argue that further developments in our ability to characterize the
      data mathematically could enable much more powerful statistical analyses.

PMID- 20690639
TI  - Nanostructured coatings by adhesion of phosphonated polystyrene particles onto
      titanium surface for implant material applications.
AB  - Titanium that is covered with a native oxide layer is widely used as an implant
      material; however, it is only passively incorporated in the human bone. To
      increase the implant-bone interaction, one can graft multifunctional phosphonic
      compounds onto the implant material. Phosphonate groups show excellent adhesion
      properties onto metal oxide surfaces such as titanium dioxide, and therefore,
      they can be used as anchor groups. Here, we present an alternative coating
      material composed of phosphonate surface-functionalized polystyrene nanoparticles
      synthesized via free radical copolymerization in a direct (oil-in-water)
      miniemulsion process. Two types of functional monomers, namely, vinylphosphonic
      acid (VPA) and vinylbenzyl phosphonic acid (VBPA), were employed in the
      copolymerization reaction. Using VBPA as a comonomer leads to particles with a
      higher density of surface phosphonate groups in comparison to those obtained with
      VPA. VBPA-functionalized particles were used for the coating formation on the
      titanium surface. The particles monolayer was investigated by scanning electron
      microscopy (SEM) and atomic force microscopy (AFM) employing titanium and
      silicium tip with the native OH groups. Force versus distance curves proves the
      strong adhesion between the phosphonated particles and the titanium (or silicium)
      surfaces in contrast to the nonfunctionalized polystyrene particles. Finally, as
      a proof of concept, the particles adhered to the surface were further used to
      nucleate hydroxyapatite, which has high potential for bioimplants.

PMID- 20690641
TI  - Versatile phosphoramidation reactions for nucleic acid conjugations with
      peptides, proteins, chromophores, and biotin derivatives.
AB  - Chemical conjugations of nucleic acids with macromolecules or small molecules are
      common approaches to study nucleic acids in chemistry and biology and to exploit
      nucleic acids for medical applications. The conjugation of nucleic acids such as
      oligonucleotides with peptides is especially useful to circumvent cell delivery
      and specificity problems of oligonucleotides as therapeutic agents. However,
      current approaches are limited and inefficient in their ability to afford peptide
      oligonucleotide conjugates (POCs). Here, we report an effective and reproducible
      approach to prepare POCs and other nucleic acid conjugates based on a newly
      developed nucleic acid phosphoramidation method. The development of a new nucleic
      acid phosphoramidation reaction was achieved by our successful synthesis of a
      novel amine-containing biotin derivative used to systematically optimize the
      reactions. The improved phosphoramidation reactions dramatically increased yields
      of nucleic acid-biotin conjugates up to 80% after 3 h reaction. Any nucleic acids
      with a terminal phosphate group are suitable reactants in phosphoramidation
      reactions to conjugate with amine-containing molecules such as biotin and
      fluorescein derivatives, proteins, and, most importantly, peptides to enable the
      synthesis of POCs for therapeutic applications. Polymerase chain reactions (PCRs)
      to study incorporation of biotin or fluorescein-tagged DNA primers into the
      reaction products demonstrated that appropriate controls of nucleic acid
      phosphoramidation reactions incur minimum adverse effects on inherited base
      pairing characteristics of nucleotides in nucleic acids. The phosphoramidation
      approach preserves the integrity of hybridization specificity in nucleic acids
      when preparing POCs. By retaining integrity of the nucleic acids, their
      effectiveness as therapeutic reagents for gene silencing, gene therapy, and RNA
      interference is ensured. The potential for POC use was demonstrated by two-step
      phosphoramidation reactions to successfully synthesize nucleic acid-tetraglycine
      conjugates. In addition, phosphoramidation reactions provided a facile approach
      to prepare nucleic acid-BSA conjugates with good yields. In summary, the new
      approach to phosphoramidation reactions offers a universal method to prepare POCs
      and other nucleic acid conjugates with high yields in aqueous solutions. The
      methods can be easily adapted to typical chemistry or biology laboratory setups
      which will expedite the applications of POCs for basic research and medicine.

PMID- 20690642
TI  - Polypeptide grafted hyaluronan: synthesis and characterization.
AB  - Poly(l-leucine) grafted hyaluronan (HA-g-PLeu) has been synthesized via a Michael
      addition reaction between primary amine terminated poly(l-leucine) and acrylate
      functionalized HA (TBAHA-acrylate). The precursor hyaluronan was first
      functionalized with acrylate groups by reaction with acryloyl chloride in the
      presence of triethylamine in N,N-dimethylformamide. (1)H NMR analysis of the
      resulting product indicated that an increase in the concentration of
      acryloylchoride with respect to hydroxyl groups on HA has only a moderate effect
      on functionalization efficiency, f. A precise control of stoichiometry was not
      achieved, which could be attributed to partial solubility of intermolecular
      aggregates and the hygroscopic nature of HA. Michael addition at high [PLeu
      NH(2)]/[acrylate](TBAHA) ratios gave a molar grafting ratio of only 0.20 with
      respect to the repeat unit of HA, indicating grafting limitation due to
      insolubility of the grafted HA-g-PLeu. Soluble HA-g-PLeu graft copolymers were
      obtained for low grafting ratios (<0.039) with <8.6% by mass of PLeu and were
      characterized thoroughly using light scattering, (1)H NMR, FT-IR, and AFM
      techniques. Light scattering experiments showed a strong hydrophobic interaction
      between PLeu chains, resulting in aggregates with segregated nongrafted HA
      segments. This yields local networks of aggregates, as demonstrated by atomic
      force microscopy. Circular dichroism spectroscopy showed a beta-sheet
      conformation for aggregates of poly(l-leucine).

PMID- 20690643
TI  - Investigation of the histamine H3 receptor binding site. Design and synthesis of
      hybrid agonists with a lipophilic side chain.
AB  - As a part of our search for novel histamine H3 receptor agonists, we designed and
      synthesized hybrid compounds in which the lipophilic (4'-alkylphenylthio)ethyl
      moiety of a novel H3 receptor agonist, 4-(2-(4'-tert-butylphenylthio)ethyl)-1H
      imidazole (1), was incorporated into N(alpha)-methylhistamine, immepip, and
      immethridine derivatives. These hybrid compounds were expected to interact
      concurrently with the histamine-binding site and a putative hydrophobic region in
      the H3 receptor. Among them, piperidine- and pyridine-type derivatives displayed
      partial agonist activity, and (S)-4-(1-(1H-imidazol-4-yl)-2-(4
      (trifluoromethyl)phenylthio)ethyl)piperidine (36) was identified as a potent H3
      agonist. We performed computational docking studies to examine the binding mode
      of the agonists. The results indicated that immepip interacts with the key
      residues, Asp114 and Glu206, in a different manner from histamine. The binding
      mode of 36 to these residues is similar to that of immepip, and the lipophilic
      tail of 36 has an additional interaction with a hydrophobic region in
      transmembrane helix 6 of the receptor. These results indicated that 36 served as
      a useful tool for studies on receptor-agonist interactions and drug design.

PMID- 20690644
TI  - Conductive cable fibers with insulating surface prepared by coaxial
      electrospinning of multiwalled nanotubes and cellulose.
AB  - Core-sheath multiwalled carbon nanotube (MWNT)-cellulose fibers of diameters from
      several hundreds of nanometers to several micrometers were prepared by coaxial
      electrospinning from a nonvolatile, nonflammable ionic liquid (IL) solvent, 1
      methyl-3-methylimidazolium acetate ([EMIM][Ac]). MWNTs were dispersed in IL to
      form a gel solution. This gel core solution was electrospun surrounded by a
      sheath solution of cellulose dissolved in the same IL. Electrospun fibers were
      collected in a coagulation bath containing ethanol-water to remove the IL
      completely and dried to form core-sheath MWNT-cellulose fibers having a cable
      structure with a conductive core and insulating sheath. Enzymatic treatment of a
      portion of a mat of these fibers with cellulase selectively removed the cellulose
      sheath exposing the MWNT core for connection to an electrode. These MWNT
      cellulose fiber mats demonstrated excellent conductivity because of a conductive
      pathway of bundled MWNTs. Fiber mat conductivity increased with increasing ratio
      of MWNT in the fibers with a maximum conductivity of 10.7 S/m obtained at 45 wt %
      MWNT loading.

PMID- 20690645
TI  - Comparison of methods for accurate quantification of DNA mass concentration with
      traceability to the international system of units.
AB  - Accurate estimation of total DNA concentration (mass concentration, e.g., ng/muL)
      that is traceable to the International System of Units (SI) is a crucial starting
      point for improving reproducible measurements in many applications involving
      nucleic acid testing and requires a DNA reference material which has been
      certified for its total DNA concentration. In this study, the concentrations of
      six different lambda DNA preparations were determined using different measurement
      platforms: UV Absorbance at 260 nm (A(260)) with and without prior sodium
      hydroxide (NaOH) treatment of the DNA, PicoGreen assay, and digital polymerase
      chain reaction (dPCR). DNA concentration estimates by A(260) with and without
      prior NaOH treatment were significantly different for five of the six samples
      tested. There were no significant differences in concentration estimates based on
      A(260) with prior NaOH treatment, PicoGreen analysis, and dPCR for two of the
      three samples tested using dPCR. Since the measurand in dPCR is amount (copy
      number) concentration (copies/muL), the results suggest that accurate estimation
      of DNA mass concentration based on copy number concentration is achievable
      provided the DNA is fully characterized and in the double-stranded form or
      amplification is designed to be initiated from only one of the two complementary
      strands.

PMID- 20690646
TI  - Synthesis and characterization of nitroimidazole derivatives for 68Ga-labeling
      and testing in tumor xenografted mice.
AB  - Radiolabeled nitroimidazole (NI) derivatives have been used for imaging hypoxic
      tissues. We synthesized NI derivatives conjugated with bifunctional chelating
      agents such as 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) and
      isothiocyanatobenzyl-NOTA (SCN-NOTA) via ethyleneamine bridge by formation of
      amide and thiourea bond, respectively. We proved that amide oxygen of Ga-NOTA-NI
      contributes to the formation of metal complex by X-ray crystallography. We
      labeled them with (68)Ga and found that both (68)Ga-NOTA-NI and (68)Ga- SCN-NOTA
      NI were labeled in high efficiency (>96%) and were stable at room temperature in
      the prepared medium and at 37 degrees C in human serum. In vitro cell uptake
      experiments using CHO and CT-26 cell lines showed significantly increased uptakes
      of both of the agents in hypoxic condition. Biodistribution study in CT-26
      xenografted mice showed increasing tumor to muscle ratios. (68)Ga-NOTA-NI showed
      lower intestine uptake than (68)Ga-NOTA-SCN-NI due to hydrophilicity. Also,
      (68)Ga-NOTA-NI showed higher tumor uptake than (68)Ga-NOTA-SCN-NI in an animal
      PET study. In conclusion, we successfully developed (68)Ga labeled NI derivatives
      for hypoxic tissue imaging.

PMID- 20690648
TI  - Conformational space and vibrational spectra of methyl 4-chloro-5-phenyl-1,3
      oxazole-2-carboxylate.
AB  - Methyl 4-chloro-5-phenyl-1,3-oxazole-2-carboxylate (MCPOC) has been synthesized
      and isolated in cryogenic matrices (argon and xenon). FTIR spectroscopy studies
      on the matrix isolated compound, supported by DFT(B3LYP)/6-311++G(d,p)
      calculations, allow for the identification of two low-energy conformers (I and
      II) of the molecule, which differ from each other in the orientation of the ester
      group relative to the oxazole ring. In both these conformers, the ester moiety is
      in the s-cis configuration (O horizontal lineC-O-CH(3) dihedral: 0 degrees ).
      Conformer II is ca. 3.0 kJ mol(-1) higher in energy than form I in the gas phase.
      Two additional higher energy conformers, III and IV, with relative energies of
      ca. 30 and 45 kJ mol(-1), respectively, were predicted to exist by the
      calculations, corresponding to structures where the ester group is in an
      approximately s-trans arrangement. Annealing of the compound isolated in xenon at
      60 K led to aggregation and simultaneous reduction of the population of I
      compared to that of the more polar conformer II. These results suggest the
      inversion of the order of stability of the two conformers in that matrix,
      eventually accompanied by a higher trend of conformer I to aggregate. Full
      assignment of the observed infrared bands to the two experimentally accessible
      conformers was carried out for the matrix isolated monomeric species. In
      addition, the infrared spectra of the neat compound in the low-temperature (10 K)
      amorphous and crystalline phases, as well as the infrared and Raman spectra of
      the crystal at room temperature were also obtained and assigned.

PMID- 20690647
TI  - Peptidyl alpha-ketoamides with nucleobases, methylpiperazine, and
      dimethylaminoalkyl substituents as calpain inhibitors.
AB  - A series of peptidyl alpha-ketoamides with the general structure Cbz-L-Leu-D,L-AA
      CONH-R were synthesized and evaluated as inhibitors for the cysteine proteases
      calpain I, calpain II, and cathepsin B. Nucleobases, methylpiperazine, and
      dimethylaminoalkyl groups were incorporated into the primed region of the
      inhibitors to generate compounds that potentially cross the blood-brain barrier.
      Two of these compounds (Cbz-Leu-D,L-Abu-CONH-(CH(2))(3)-adenin-9-yl and Cbz-Leu
      D,L-Abu-CONH-(CH(2))(3)-(4-methylpiperazin-1-yl) have been shown to have useful
      concentrations in the brain in animals. The best inhibitor for calpain I was Cbz
      Leu-D,L-Abu-CONH-(CH(2))(3)-2-methoxyadenin-9-yl (K(i) = 23 nM), and the best
      inhibitor for calpain II was Cbz-Leu-D,L-Phe-CONH-(CH(2))(3)-adenin-9-yl (K(i) =
      68 nM). On the basis of the crystal structure obtained with heterocyclic peptidyl
      alpha-ketoamides, we have improved inhibitor potency by introducing a small
      hydrophobic group on the adenine ring. These inhibitors have good potential to be
      used in the treatment of neurodegenerative diseases.

PMID- 20690649
TI  - Phase behavior of a binary mixture of 1,3-dipalmitoyl-2-oleoyl-sn-glycerol and
      1,3-dioleoyl-2-palmitoyl-sn-glycerol in n-dodecane solution.
AB  - The phase behavior of a binary mixture of triacylglycerol (TAG), POP (1,3
      dipalmitoyl-2-oleoyl-sn-glycerol), and OPO (1,3-dioleoyl-2-palmitoyl-sn-glycerol)
      in an organic solvent, n-dodecane, was examined by DSC and synchrotron radiation
      X-ray diffraction (SR-XRD). In our previous study on POP-OPO mixtures in neat
      liquid, the formation of molecular compound (MC) crystals of POP/OPO = 50/50 was
      observed (Minato et al. J. Am. Oil Chem. Soc. 1997, 74, 1213-1220). The purpose
      of the present study was to determine whether MC is formed in the POP-OPO mixture
      system in diluted solution when n-dodecane (C(12)) is added to the mixture as a
      solvent. Two solution systems having weight concentration ratios of POP and OPO
      to n-dodecane ((POP+OPO):C(12)) of 50:50 (50% solution) and 20:80 (20% solution)
      were prepared. We found that MC formed at a ratio of POP/OPO = 50/50 in both 50%
      solution and 20% solution in the stable and metastable states. Differences
      between the neat liquid and solution systems appeared in two results. In the
      first, the melting temperatures of MC crystals were lowered from 32.0 degrees C
      (neat liquid) to 20.4 degrees C (50% solution) and 18.0 degrees C (20% solution).
      In the second, the beta polymorph of the MC was always observed in the two
      solutions under the conditions examined in the present study, whereas alpha and
      beta polymorphs were observed in the neat liquid. These differences were caused
      by thermodynamic solvent effects. However, we conclude that aliphatic chain-chain
      interactions through palmitic and oleic acid moieties forming the MC of POP-OPO
      having a double chain length structure are not disturbed by solute-solvent
      interactions.

PMID- 20690650
TI  - The rate-limiting step in P450 hydroxylation of hydrocarbons a direct comparison
      of the "somersault" versus the "consensus" mechanism involving compound I.
AB  - Model theoretical quantum mechanical (QM) calculations are described for the P
      450 hydroxylation of methane, isobutane, and camphor that compare the concerted
      somersault H-abstraction mechanism with the oxidation step involving Cpd I.
      Special emphasis has been placed on maintaining a balanced basis set in the
      oxidation step. QM calculations, employing the 6-311+G(d,p) basis set on the Fe
      atom and all of the key surrounding atoms involved in the C-H abstraction step,
      reaffirm a mechanism involving rearrangement of the iron hydroperoxide group (FeO
      OH --> FeO...HO(*)) in concert with hydrogen abstraction from the C-H bond of the
      substrate by the incipient bound hydroxyl radical HO(*). The barrier for the
      somersault rearrangement of model Cpd 0 (FeO-OH) is calculated to be 21.4
      kcal/mol in the absence of substrate. The overall activation energy for the
      oxidation of camphor involving the somersault motion of the FeO-OH group of P450
      model porphyrin iron(III) hydroperoxide [Por(SH)Fe(III)-OOH(-)] -->
      [Por(SH)Fe(III)-O....HO(-)] in concert with hydrogen abstraction is DeltaE(++) =
      12.4 kcal/mol. The corresponding abstraction of the hydrogen atom from the C-H
      bond of camphor by Cpd I has an activation barrier of 17.6 kcal/mol. Arguments
      are presented that the somersault rearrangement is induced by steric compression
      at the active site. Kinetic isotope effect data are discussed that provides
      compelling evidence for a rate-limiting step involving C-H bond cleavage.

PMID- 20690651
TI  - Dynamical characterization of a cellulose acetate polysaccharide.
AB  - This work brings together dynamical and structural information at a molecular
      level for cellulose acetate being an original contribution to the general
      description of polysaccharide properties. In particular, it allowed
      reinterpreting the secondary relaxation mechanisms that are still controversial
      in the literature; a compilation of data provided by different authors is
      provided. Detailed dynamical information is provided by dielectric relaxation
      spectroscopy (DRS) (10(-1)-10(6) Hz) for cellulose acetate (CA) in the sub-T(g)
      region below ambient temperature; results were compared with cellulose acetate
      structured as an asymmetric membrane (CAmb). In samples with low water content,
      two secondary relaxation processes between 173 and 298 K were identified by DRS,
      associated with localized mobility. The process located at the lowest
      temperatures (process I) has a different mobility in CA relative to CAmb. The
      identical crystalline/amorphous state of both materials allowed rationalizing the
      distinct behavior in terms of polymeric arrangement and ability for water uptake.
      The looser structure of the CA relative to CAmb as confirmed by FTIR, TGA, and
      DSC analysis makes more sites accessible to water molecules, resulting in a
      higher water retention in CA (2.73% w/w) relative to CAmb (1.60% w/w) and an
      increased molecular mobility in the former due to a plasticizing effect. In both
      materials, process I is significantly influenced by hydration, shifting to higher
      frequencies and lower temperatures upon water uptake. This process seems to be
      associated with mobility occurring within the monomeric unit, which embraces the
      two anhydroglucose rings connected by the glycosidic linkage and the polar groups
      directly attached to it. It should involve a very limited length scale, as
      suggested by its location, far below the glass transition, and the tau(infinity)
      value with a low entropic effect. The relaxation process that emerges later,
      process II, is similar for both samples being much less influenced by water but
      experiencing a slight antiplasticizing effect shifting to lower frequencies and
      higher temperatures upon hydration. It should involve side group motions,
      strongly coupled to the mobility of the anhydroglucose rings, which become
      hindered probably due to establishment of H-bonds with water molecules. The
      plasticizing/antiplasticizing effect is being discussed only on the basis of the
      frequency position of the relaxation peak. Processes I and II merge into a broad
      relaxation (gamma(dry)) upon water removal in both CA and CAmb, however evolving
      slower in the former with drying, due to a more disordered structure of CA that
      allows water to interact with more internal sites in the polymer. At higher
      temperatures (T > or = 353 K), a process emerges in the high frequency side of
      the dynamic alpha-relaxation which is compatible with a beta(JG)-relaxation. The
      structured specimen CAmb provided an additional way to probe the morphological
      changes undergone by the material when annealed to temperatures higher than 353
      K, originating an increase in the dielectric response. This effect can be
      associated with a skin densification and partial collapse of the membrane porous
      network, as observed by SEM.

PMID- 20690652
TI  - Membrane interactions of novicidin, a novel antimicrobial peptide:
      phosphatidylglycerol promotes bilayer insertion.
AB  - Novicidin is an antimicrobial peptide derived from ovispirin, a cationic peptide
      which originated from the ovine cathelicidin SMAP-29. Novicidin, however, has
      been designed to minimize the cytotoxic properties of SMAP-29 and ovisipirin
      toward achieving potential therapeutic applications. We present an analysis of
      membrane interactions and lipid bilayer penetration of novicidin, using an array
      of biophysical techniques and biomimetic membrane assemblies, complemented by
      Monte Carlo (MC) simulations. The data indicate that novicidin interacts
      minimally with zwitterionic bilayers, accounting for its low hemolytic activity.
      Negatively charged phosphatidylglycerol, on the other hand, plays a significant
      role in initiating membrane binding of novicidin, and promotes peptide insertion
      into the interface between the lipid headgroups and the acyl chains. The
      significant insertion into bilayers containing negative phospholipids might
      explain the enhanced antibacterial properties of novicidin. Overall, this study
      highlights two distinct outcomes for membrane interactions of novicidin, and
      points to a combination between electrostatic attraction to the lipid/water
      interface and penetration into the subsurface lipid headgroups region as
      important determinants for the biological activity of novicidin.

PMID- 20690653
TI  - Electrocapillarity under ultraslow relaxation of the ionic liquid double layer at
      the interface between trioctylmethylammonium bis(nonafluorobutanesulfonyl)amide
      and water.
AB  - Electrocapillarity has been studied in detail at the interface between a
      hydrophobic ionic liquid (IL), trioctylmethylammonium
      bis(nonafluorobutanesulfonyl)amide, and water, where the ultraslow relaxation of
      the structure of the electrical double layer on the IL side of the interface
      exists. The response of the interfacial tension and that of the charging current
      to the potential step can be fitted by a double exponential model having the
      relaxation time constants of a few seconds and 100 s. The hysteresis in the
      interfacial tension in the IL diluted with nitrobenzene persists even in an
      almost 1:1 mixture of the IL and nitrobenzene. The thermodynamically definable
      double layer capacitance (C(dl)) estimated from the equilibrated electrocapillary
      curve, that is, the interfacial tension versus potential curve, at the IL|water
      interface has a maximum value of about 60 microF cm(-2) in the vicinity of the
      potential of zero charge (pzc) when the aqueous phase is 0.1 mol dm(-3) LiCl. The
      C(dl) versus the potential plot shows a characteristic camelback shape, showing a
      shallow minimum at the pzc, where the C(dl) value is 42 microF cm(-2). This
      minimum seems to reflect the contribution of C(dl) on the aqueous side of the
      interface to the total capacitance.

PMID- 20690654
TI  - Catalytic reduction of NO2 with hydrogen on Pt field emitter tips: kinetic
      instabilities on the nanoscale.
AB  - The catalytic reduction of NO(2) with hydrogen on a Pt field emitter tip is
      investigated using both field electron microscopy (FEM) and field ion microscopy
      (FIM). A rich variety of nonlinear behavior and unusually high catalytic activity
      around the {012} facets are observed. Our FEM investigations reveal that the
      correlation function exhibits damped oscillations with a decaying envelope,
      showing that molecular noise will influence the dynamics of the oscillations. The
      dependence of the oscillatory period on the P(H(2))/P(NO(2)) pressure ratios is
      analyzed. Similar patterns are reported under FIM conditions. Corresponding
      density functional theory (DFT) calculations for the adsorption of NO(2) on
      Pt{012} in the presence of an external electric field are performed in order to
      gain an atomistic understanding of the underlying nonlinear phenomena.

PMID- 20690655
TI  - WizePairZ: a novel algorithm to identify, encode, and exploit matched molecular
      pairs with unspecified cores in medicinal chemistry.
AB  - An algorithm to automatically identify and extract matched molecular pairs from a
      collection of compounds has been developed, allowing the learning associated with
      each molecular transformation to be readily exploited in drug discovery projects.
      Here, we present the application to an example data set of 11 histone deacetylase
      inhibitors. The matched pairs were identified, and corresponding differences in
      activity and lipophilicity were recorded. These property differences were
      associated with the chemical transformations encoded in the SMIRKS reaction
      notation. The transformations identified a subseries with the optimal balance of
      these two parameters. Enumeration of a virtual library of compounds using the
      extracted transformations identified two additional compounds initially excluded
      from the analysis with an accurate estimation of their biological activity. We
      describe how the WizePairZ system can be used to archive and apply medicinal
      chemistry knowledge from one drug discovery project to another as well as
      identify common bioisosteres.

PMID- 20690656
TI  - Pocket similarity: are alpha carbons enough?
AB  - A novel method for measuring protein pocket similarity was devised, using only
      the alpha carbon positions of the pocket residues. Pockets were compared pairwise
      using an exhaustive three-dimensional Calpha common subset search, grouping
      residues by physicochemical properties. At least five Calpha matches were
      required for each hit, and distances between corresponding points were fit to an
      Extreme Value Distribution resulting in a probabilistic score or likelihood for
      any given superposition. A set of 85 structures from 13 diverse protein families
      was clustered based on binding sites alone, using this score. It was also
      successfully used to cluster 25 kinases into a number of subfamilies. Using a
      test kinase query to retrieve other kinase pockets, it was found that a
      specificity of 99.2% and sensitivity of 97.5% could be achieved using an
      appropriate cutoff score. The search itself took from 2 to 10 min on a single 3.4
      GHz CPU to search the entire Protein Data Bank (133 800 pockets), depending on
      the number of hits returned.

PMID- 20690657
TI  - Derivitization of pristine graphene with well-defined chemical functionalities.
AB  - Covalent functionalization of pristine graphene poses considerable challenges due
      to the lack of reactive functional groups. Herein, we report a simple and general
      method to covalently functionalize pristine graphene with well-defined chemical
      functionalities. It is a solution-based process where solvent-exfoliated graphene
      was treated with perfluorophenylazide (PFPA) by photochemical or thermal
      activation. Graphene with well-defined functionalities was synthesized, and the
      resulting materials were soluble in organic solvents or water depending on the
      nature of the functional group on PFPA.

PMID- 20690658
TI  - Development and application of a milli-whistle for use in gas chromatography
      detection.
AB  - A simple milli-whistle was developed for the use in GC (gas chromatography)
      detection, in which, compared to a thermal conductivity detector (TCD), 1 order
      of magnitude superior sensitivity can be obtained. The milli-whistle can be
      connected to the outlet of a GC capillary. The gas and makeup gas passing through
      the capillary produces a sound as it passes through the milli-whistle (i.e., the
      gas of the GC eluate). The sound can easily be detected by a microphone, which,
      after a Fourier transform (FT) by means of a LabVIEW (Laboratory Virtual
      Instrumentation Engineering Workbench) built-in program, a very sharp frequency
      peak (full width at half-maximum, approximately 1.6 Hz) can be simultaneously
      observed. As a result, GC elutes can be qualitatively determined on the basis of
      their retention times, and a quantitative analysis can be achieved on the basis
      of the frequency shifts. When the makeup and carrier gases used were nitrogen, in
      the case of gas samples, including hydrogen, helium, argon, and carbon dioxide,
      the limits of detection were found to be approximately 3 microL/each injection;
      in the case of liquid samples, including methanol, cyclohexane, tetrahydrofuran,
      hexane, and acetone, the limits of detection were determined to be approximately
      10 microg/each injection, respectively. When the gases were changed to hydrogen,
      the limits of detection were dramatically improved. When acetone was selected as
      the model sample, a linear relationship was found in the range of 0.2-200
      microg/injection.

PMID- 20690659
TI  - Microhydration of the selenite dianion: a theoretical study of structures,
      hydration energies, and electronic stabilities of SeO(3)(2-)(H(2)O)(n) (n = 0-6,
      9) clusters.
AB  - In extension of the ongoing investigations of oxyanion-water clusters, we studied
      energetically low-lying configurations of hydrated selenite dianion (and in
      select cases, SeO(3)(-)) clusters using density functional theory (B3LYP, M05-2X,
      PBE0) and second-order Moller-Plesset perturbation theory (MP2). Water molecules
      doubly hydrogen bond to the selenite oxygens for n <or= 3 and increasingly form
      singly hydrogen bonds with selenite oxygens upon an increase of the cluster size
      as water-water interactions gain relative importance as compared to the selenite
      water interactions. The calculated average Se-O bond length of 1.69-1.71 A and
      selenite tetrahedron height of 0.64-0.73 A are in accordance with recent
      experimental results for selenite in aqueous solution or adsorbed on calcite.
      Structural perturbations due to the hydration are accompanied by a considerable
      charge transfer (up to 0.55|e|) from the selenite substructure to the water
      molecules. Furthermore, the calculated electron binding energies evidence that
      selenite-water clusters are electronically stable only for n >or= 4 (according to
      M05-2X) or n >or= 5 (according to B3LYP and PBE0). The hitherto unknown hydration
      free energy of selenite was calculated using a cluster/continuum approach to fall
      into the range from -224.6 to -245.5 kcal/mol depending on the applied continuum
      solvation model.

PMID- 20690660
TI  - Substituent effects on the reaction of beta-benzoylalanines with Pseudomonas
      fluorescens kynureninase.
AB  - Kynureninase is a pyridoxal 5'-phosphate-dependent enzyme that catalyzes the
      hydrolytic cleavage of l-kynurenine to give l-alanine and anthranilic acid. beta
      Benzoyl-l-alanine, the analogue of l-kynurenine lacking the aromatic amino group,
      was shown to a good substrate for kynureninase from Pseudomonas fluorescens, and
      the rate-determining step changes from release of the second product, l-Ala, to
      formation of the first product, benzoate [Gawandi, V. B., et al. (2004)
      Biochemistry 43, 3230-3237]. In this work, a series of aryl-substituted beta
      benzoyl-dl-alanines was synthesized and evaluated for substrate activity with
      kynureninase from P. fluorescens. Hammett analysis of k(cat) and k(cat)/K(m) for
      4-substituted beta-benzoyl-dl-alanines with electron-withdrawing and electron
      donating substituents is nonlinear, with a concave downward curvature. This
      suggests that there is a change in rate-determining step for benzoate formation
      with different substituents, from gem-diol formation for electron-donating
      substituents to C(beta)-C(gamma) bond cleavage for electron-withdrawing
      substituents. Rapid-scanning stopped-flow kinetic experiments demonstrated that
      substituents have relatively minor effects on formation of the quinonoid and 348
      nm intermediates but have a much greater effect on the formation of the aldol
      product from reaction of benzaldehyde with the 348 nm intermediate. Since there
      is a kinetic isotope effect on its formation from beta,beta-dideuterio-beta-(4
      trifluoromethylbenzoyl)-dl-alanine, the 348 nm intermediate is proposed to be a
      vinylogous amide derived from abortive beta-deprotonation of the ketimine
      intermediate. These results provide additional evidence for a gem-diol
      intermediate in the catalytic mechanism of kynureninase.

PMID- 20690661
TI  - Titanium(IV) chloride-mediated carbon-carbon bond-forming reaction between 3,3
      dialkylcyclobutanones and aldehydes.
AB  - Treatment of 3,3-dialkylcyclobutanones with titanium(IV) chloride in the presence
      of aldehyde gave beta'-chloro-beta-hydroxy ketones in high yields. It was
      speculated that ring cleavage of the cyclobutanone ring with titanium(IV)
      chloride gave trichlorotitanium enolate having a tertiary alkyl chloride moiety
      and then aldol reaction of the titanium enolate proceeded. A trialkylsilylmethyl
      group at the 2-position of cyclobutanone facilitated the ring cleavage. Synthesis
      of substituted cyclopentenone from an obtained product is also described.

PMID- 20690662
TI  - Chiral Bronsted acid-catalyzed allylboration of aldehydes.
AB  - The catalytic enantioselective allylation of aldehydes is a long-standing problem
      of considerable interest to the chemical community. We disclose a new high
      yielding and highly enantioselective chiral Bronsted acid-catalyzed allylboration
      of aldehydes. The reaction is shown to be highly general, with a broad substrate
      scope that covers aryl, heteroaryl, alpha,beta-unsaturated, and aliphatic
      aldehydes. The reaction conditions are also shown to be effective for the
      catalytic enantioselective crotylation of aldehydes. We believe that the high
      reactivity of the allylboronate is due to protonation of the boronate oxygen by
      the chiral phosphoric acid catalyst.

PMID- 20690663
TI  - Proteomic analysis of human osteoblastic cells: relevant proteins and functional
      categories for differentiation.
AB  - Osteoblasts are the bone forming cells, capable of secreting an extracellular
      matrix with mineralization potential. The exact mechanism by which osteoblasts
      differentiate and form a mineralized extracellular matrix is presently not fully
      understood. To increase our knowledge about this process, we conducted proteomics
      analysis in human immortalized preosteoblasts (SV-HFO) able to differentiate and
      mineralize. We identified 381 proteins expressed during the time course of
      osteoblast differentiation. Gene ontology analysis revealed an overrepresentation
      of protein categories established as important players for osteoblast
      differentiation, bone formation, and mineralization such as pyrophosphatases.
      Proteins involved in antigen presentation, energy metabolism and cytoskeleton
      rearrangement constitute other overrepresented processes, whose function, albeit
      interesting, is not fully understood in the context of osteoblast differentiation
      and bone formation. Correlation analysis, based on quantitative data, revealed a
      biphasic osteoblast differentiation, encompassing a premineralization and a
      mineralization period. Identified differentially expressed proteins between
      mineralized and nonmineralized cells include cytoskeleton (e.g., CCT2, PLEC1, and
      FLNA) and extracellular matrix constituents (FN1, ANXA2, and LGALS1) among
      others. FT-ICR-MS data obtained for FN1, ANXA2, and LMNA shows a specific
      regulation of these proteins during the different phases of osteoblast
      differentiation. Taken together, this study increases our understanding of the
      proteomics changes that accompany osteoblast differentiation and may permit the
      discovery of novel modulators of bone formation.

PMID- 20690664
TI  - Serum and urinary metabonomic study of human osteosarcoma.
AB  - Osteosarcoma (OS) is the most common malignant bone tumor found in children.
      Currently, researchers have focused on protein and gene levels, while the
      associated metabolic variations have been poorly understood. In this study, we
      used a gas chromatography mass spectrometry approach and profiled small-molecule
      metabolites in serum and urine of 24 OS patients, 19 benign bone tumor patients,
      and 32 healthy controls, to determine whether there are significant alterations
      associated with carcinogenesis. The metabonomic results demonstrate clear
      intergroup separations between healthy control subjects and bone tumor patients
      in the orthogonal partial least-squares-discriminant analysis (OPLS-DA) models.
      Differential metabolites identified from the metabonomic analysis suggest a
      disrupted energy metabolism in OS patients, as characterized by significantly
      down-regulated TCA cycle and glycolysis, down-regulated lipid metabolism,
      dysregulated sugar levels, and up-regulated amino acid metabolism. Additionally,
      an increased activity of glutathione metabolism, and increased polyamine
      metabolism also contributed to a characteristic metabolic signature of OS
      patients.

PMID- 20690665
TI  - A proteome-scale identification of novel antigenic proteins in Mycobacterium
      tuberculosis toward diagnostic and vaccine development.
AB  - Tuberculosis (TB) remains to be a major infectious disease throughout the world.
      However, the current vaccine for TB has variable protective efficacy, and there
      is no commercially available serodiagnostic test for this disease with acceptable
      sensitivity and specificity for routine laboratory use. One of the potential
      strategies in developing a new diagnostic method and in improving the TB vaccine
      involves the identification of novel antigenic candidates. This paper aims to
      identify systematically the novel antigenic proteins with the greatest potential
      as protective or diagnostic antigens by using the differential response of
      Mycobacterium tuberculosis proteins to serum from TB patients and healthy
      individuals. Approximately 87% of the open reading frames of M. tuberculosis were
      successfully cloned into IPTG-inducible expression vectors. The clone sets were
      expressed in Escherichia coli, purified under denatured conditions, and tested
      for antigenicity using a mixture of sera from 15 TB patients. Out of the 3480
      proteins screened, 249 proteins had significant reactions with the serum samples.
      Among the 249 proteins, 20 proteins were identified as most reactive. Compared
      with the commercial test kits, 3 novel antigens from the top 20 proteins, namely,
      Rv1987, Rv3807c, and Rv3887c, provided better sensitivity and accuracy. These
      newly identified antigenic proteins may be used as candidates for serodiagnostic
      application and vaccine development. Overall, this study's findings may serve as
      an essential reference for developing new TB diagnostic methods and more
      effective tuberculosis vaccines.

PMID- 20690666
TI  - CE-MS for metabolic profiling of volume-limited urine samples: application to
      accelerated aging TTD mice.
AB  - Metabolic profiling of biological samples is increasingly used to obtain more
      insight into the pathophysiology of diseases. For translational studies,
      biological samples from animal models are explored; however, the volume of these
      samples can be a limiting factor for metabolic profiling studies. For instance,
      only a few microliters of urine is often available from small animals like mice.
      Hence, there is a need for a tailor-made analytical method for metabolic
      profiling of volume-limited samples. In the present study, the feasibility of
      capillary electrophoresis time-of-flight mass spectrometry (CE-ToF-MS) for
      metabolic profiling of urine from mice is evaluated. Special attention is paid to
      the analytical workflow; that is, such aspects as sample preparation, analysis,
      and data treatment are discussed from the metabolomics viewpoint. We show that
      metabolites belonging to several chemical families can be analyzed in mouse urine
      with the CE-ToF-MS method using minimal sample pretreatment and an in-capillary
      preconcentration procedure. This exemplifies the advantages of CE-ToF-MS for
      metabolic profiling of volume-limited samples as loss of material is minimized.
      The feasibility of the CE-ToF-MS-based workflow for metabolic profiling is
      illustrated by the analysis of urine samples from wild-type as well as from TTD
      mutant mice, which are a model for the accelerated aging, with osteoporosis being
      one of the main hallmarks.

PMID- 20690667
TI  - Layer-by-layer synthesis of metal-containing conducting polymers: caged metal
      centers for interlayer charge transport.
AB  - Metal-templated [2 + 3]-type cocondensation of a pi-extended boronic acid and
      nioxime furnished a series of cage molecules, which were electropolymerized to
      prepare metal-containing conducting polymers (MCPs). Despite sharing essentially
      isostructural organic scaffolds, these materials display metal-dependent
      electrochemical properties as evidenced by different redox windows observed for M
      = Co, Fe, Ru. Consecutive electropolymerization using two different monomers
      furnished bilayer MCPs having different metals in each layer. In addition to
      functioning as heavy atom markers in cross-sectional analysis by FIB and EDX,
      redox-active metal centers participate in voltage-dependent interlayer electron
      transport to give rise to cyclic voltammograms that are distinctively different
      from those of each layer alone or random copolymers. A simple electrochemical
      technique can thus be used as a straightforward diagnostic tool to investigate
      the structural ordering of electrically conductive layered materials.

PMID- 20690668
TI  - Role of heterogeneous precipitation in determining the nature of products formed
      on oxidation of Fe(II) in seawater containing natural organic matter.
AB  - A detailed kinetic model has been developed to describe the formation of the
      oxidation products, organically complexed Fe(III) and amorphous ferric oxide
      (AFO), on oxidation of Fe(II) in seawater containing Suwannee River fulvic acid
      (SRFA). Experimental data were collected using spectrophotometric detection of
      the Fe(III)-SRFA complex for a range of initial concentrations of Fe(II) and
      SRFA. Initial sensitivity analysis identified rate constants to which the model
      was most sensitive including those for heterogeneous precipitation of AFO and
      Fe(II)-SRFA formation and dissociation which to date have only been determined
      with a high degree of uncertainty. Using these rate constants as fitting
      parameters, an accurate fit to the experimental data could be obtained using a
      kinetic model describing key processes. However, reasonable fits could only be
      achieved with the inclusion of the heterogeneous precipitation reaction
      suggesting the importance of this reaction in determining the outcome of
      oxidation in the presence of organic ligands. The rate constants for Fe(II)-SRFA
      formation and dissociation were highly correlated and could not be determined
      uniquely, however their ratio revealed a stability constant of approximately
      10(5), 3 orders of magnitude higher than previously reported. The fitted model
      also suggested that a complex interaction between Fe(II) and SRFA in the initial
      stages of the oxidation process determines the pathway of Fe(III)-SRFA formation.

PMID- 20690669
TI  - Quantification of the binding properties of Cu2+ to the amyloid beta peptide:
      coordination spheres for human and rat peptides and implication on Cu2+-induced
      aggregation.
AB  - There is no consensus on the coordinating ligands for Cu(2+) by Abeta. However,
      the differences in peptide sequence between human and rat have been hypothesized
      to alter metal ion binding in a manner that alters Cu(2+)-induced aggregation of
      Abeta. Herein, we employ isothermal titration calorimetry (ITC), circular
      dichroism (CD), and electron paramagnetic resonance (EPR) spectroscopy to examine
      the Cu(2+) coordination spheres to human and rat Abeta and an extensive set of
      Abeta(16) mutants. EPR of the mutant peptides is consistent with a 3N1O binding
      geometry, like the native human peptide at pH 7.4. The thermodynamic data reveal
      an equilibrium between three coordination spheres, {NH(2), O, N(Im)(His6), N(-)},
      {NH(2), O, N(Im)(His6), N(Im)(His13)}, and {NH(2), O, N(Im)(His6), N(Im)(His14)},
      for human Abeta(16) but one dominant coordination for rat Abeta(16), {NH(2), O,
      N(Im)(His6), N(-)}, at pH 7.4-6.5. ITC and CD data establish that the mutation
      R5G is sufficient for reproducing this difference in Cu(2+) binding properties at
      pH 7.4. The substitution of bulky and positively charged Arg by Gly is proposed
      to stabilize the coordination {NH(2), O-, N(Im)(His6), N(-)} that then results in
      one dominating coordination sphere for the case of the rat peptide. The
      differences in the coordination geometries for Cu(2+) by the human and rat Abeta
      are proposed to contribute to the variation in the ability of Cu(2+) to induce
      aggregation of Abeta peptides.

PMID- 20690670
TI  - Probing the chemotaxis periplasmic sensor domains from Geobacter sulfurreducens
      by combined resonance Raman and molecular dynamic approaches: NO and CO sensing.
AB  - The periplasmic sensor domains encoded by genes gsu0582 and gsu0935 are part of
      methyl accepting chemotaxis proteins in the bacterium Geobacter sulfurreducens
      (Gs). The sensor domains of these proteins contain a heme-c prosthetic group and
      a PAS-like fold as revealed by their crystal structures. Biophysical studies of
      the two domains showed that nitric oxide (NO) binds to the heme in both the
      ferric and ferrous forms, whereas carbon monoxide (CO) binds only to the reduced
      form. In order to address these exogenous molecules as possible physiological
      ligands, binding studies and resonance Raman (RR) spectroscopic characterization
      of the respective CO and NO adducts were performed in this work. In the absence
      of exogenous ligands, typical RR frequencies of five-coordinated (5c) high-spin
      and six-coordinated (6c) low-spin species were observed in the oxidized form. In
      the reduced state, only frequencies corresponding to the latter were detected. In
      both sensors, CO binding yields 6c low-spin adducts by replacing the endogenous
      distal ligand. The binding of NO by the two proteins causes partial disruption of
      the proximal Fe-His bond, as revealed by the RR fingerprint features of 5cFe-NO
      and 6cNO-Fe-His species. The measured CO and NO dissociation constants of ferrous
      GSU0582 and GSU0935 sensors reveal that both proteins have high and similar
      affinity toward these molecules (K(d) approximately = 0.04-0.08 microM). On the
      contrary, in the ferric form, sensor GSU0582 showed a much higher affinity for NO
      (K(d) approximately = 0.3 microM for GSU0582 versus 17 microM for GSU0935).
      Molecular dynamics calculations revealed a more open heme pocket in GSU0935,
      which could account for the different affinities for NO. Taken together,
      spectroscopic data and MD calculations revealed subtle differences in the binding
      properties and structural features of formed CO and NO adducts, but also
      indicated a possibility that a (5c) high-spin/(6c) low-spin redox-linked
      equilibrium could drive the physiological sensing of Gs cells.

PMID- 20690671
TI  - Ab initio study of the electronic structure of zinc oxide and its ions, ZnO(0,+/
      ). Ground and excited states.
AB  - The species ZnO and ZnO(+/-) have been studied by variational multireference and
      coupled-cluster [RCCSD(T)] methods employing augmented basis sets of quintuple
      cardinality. Full potential energy curves are reported for 13, 10, and 2 bound
      states of ZnO, ZnO(+), and ZnO(-), respectively. All our results are in excellent
      agreement with existing experimental findings.

PMID- 20690672
TI  - Importance of fat oxidation in starch-based emulsions in the generation of the
      process contaminant furan.
AB  - The formation of the possibly carcinogenic process contaminant furan was studied
      in starch-based emulsions during heat treatments as applied for sterilization.
      Fresh and oxidized soybean, sunflower, high-oleic sunflower, olive, linseed, and
      rapeseed oils were compared. Results indicated that both the oil type, in
      particular, the fatty acid composition, and the oxidation degree of the oil
      determined the susceptibility of the oils to generate furan upon heating. Thus,
      oils containing the nutritionally relevant omega-3 unsaturated alpha-linolenic
      acid proved to be able to generate significant amounts of furan if the oils were
      oxidized. No clear relationship between p-anisidine values of various oils and
      the amount of generated furan could be observed. However, in the case of soybean
      oil, significantly more furan was produced upon an increase in oxidation degree.
      Surprisingly, furan formation in food-relevant systems containing fresh lipids
      proved to be a minor route (up to 1.5 ppb furan) compared to a previously studied
      vitamin C containing model system (up to 13 ppb furan).

PMID- 20690673
TI  - Testing high-level QM/MM methods for modeling enzyme reactions: acetyl-CoA
      deprotonation in citrate synthase.
AB  - Combined quantum mechanics/molecular mechanics (QM/MM) calculations with high
      levels of correlated ab initio theory can now provide benchmarks for enzyme
      catalyzed reactions. Here, we use such methods to test various QM/MM methods and
      the sensitivity of the results to details of the models for an important enzyme
      reaction, proton abstraction from acetyl-coenzyme A in citrate synthase. We
      calculate multiple QM/MM potential energy surfaces up to the local coupled
      cluster theory (LCCSD(T0)) level, with structures optimized at hybrid density
      functional theory and Hartree-Fock levels. The influence of QM methods, basis
      sets, and QM region size is shown to be significant. Correlated ab initio QM/MM
      calculations give barriers in agreement with experiment for formation of the
      acetyl-CoA enolate intermediate. In contrast, B3LYP fails to identify the enolate
      as an intermediate, whereas BH&HLYP does. The results indicate that QM/MM methods
      and setup should be tested, ideally using high-level calculations, to draw
      reliable mechanistic conclusions.

PMID- 20690674
TI  - Differential proteome profiling of eutopic endometrium from women with
      endometriosis to understand etiology of endometriosis.
AB  - The identification of molecular differences in the endometrium of women with
      endometriosis is an important step toward understanding the pathogenesis of this
      condition and for developing novel strategies for the treatment of associated
      infertility and pain. In this study, we investigated protein expression analysis
      of eutopic endometrium from women with and without endometriosis. The proteomic
      analysis revealed molecular dysregulation of more than 70 proteins in the
      proliferative phase of eutopic endometrium in stage IV and secretory phase of
      stage II, III and IV endometriosis. Using mass spectrometry, 48 proteins spots
      which were consistently differentially expressed from stage II to IV
      endometriosis were identified. The differentially expressed proteins include
      structural proteins, proteins involved in stress response, protein-folding and
      protein-turnover, immunity, energy production, signal transduction, RNA
      biogenesis, protein biosynthesis, and nuclear proteins. Immunoblot and
      immunohistochemical analyses confirmed the observed changes in eight
      representative proteins. The present study provides identification of new players
      that have a potential role in the initiation and progression of endometriosis and
      also sets a framework for further investigations on mechanisms underlying the
      pathogenesis of endometriosis.

PMID- 20690675
TI  - Catalytic C-H bond stannylation: a new regioselective pathway to C-Sn bonds via C
      H bond functionalization.
AB  - The ubiquitous Stille coupling reaction utilizes Sn-C bonds and is of great
      utility to organic chemists. Unlike the B-C bonds used in the Miyaura-Suzuki
      coupling reaction, which are readily obtained via direct borylation of C-H bonds,
      routes to organotin compounds via direct C-H bond functionalization are lacking.
      Here we report that the nickel-catalyzed reaction of fluorinated arenes and
      pyridines with vinyl stannanes does not provide the expected vinyl compounds via
      C-F activation but rather provides new Sn-C bonds via C-H functionalization with
      the loss of ethylene. This mechanism provides a new unanticipated methodology for
      the direct conversion of C-H bonds to carbon-heteroatom bonds.

PMID- 20690676
TI  - Scope and mechanism of allylic C-H amination of terminal alkenes by the
      palladium/PhI(OPiv)2 catalyst system: insights into the effect of naphthoquinone.
AB  - Palladium-catalyzed oxidative amination of unactivated alkyl olefins has been
      developed to produce linear (E)-allylimides with high regioselectivity. This
      highly efficient transformation of alkenes has been achieved by enhancing the
      reoxidation of palladium with the strong oxidant PhI(OPiv)(2). The present work
      also provides the first systematic analysis of the mechanism of the allylic C-H
      oxidative amination. It has been found that naphthoquinone (NQ) plays a vital
      role in promoting olefin coordination to the palladium catalyst: in the absence
      of NQ, the turnover-limiting step is olefin coordination to palladium catalyst;
      in the presence of NQ, the reaction involves a rapid equilibration to give a
      nitrogen-coordinated olefin-Pd(NQ) complex that undergoes turnover-limiting
      allylic C-H bond activation to generate a pi-allyl-Pd intermediate. This work
      provides valuable insights for further studies on the functionalization of
      unactivated olefins.

PMID- 20690677
TI  - Probing the rate of hole transfer in oxidized porphyrin dyads using thallium
      hyperfine clocks.
AB  - Understanding hole/electron-transfer processes among interacting constituents of
      multicomponent molecular architectures is central to the fields of artificial
      photosynthesis and molecular electronics. One strategy for examining ground-state
      hole/electron transfer in oxidized tetrapyrrolic arrays entails analysis of the
      hyperfine interactions observed in the electron paramagnetic resonance (EPR)
      spectrum of the pi-cation radical. Herein, it is demonstrated that
      (203)Tl/(205)Tl hyperfine "clocks" are greatly superior to those provided by
      (1)H, (14)N, or (13)C owing to the fact that the (203)Tl/(205)Tl hyperfine
      couplings are much larger (15-25 G) than those of the (1)H, (14)N, or (13)C
      nuclei (1-6 G). The large (203)Tl/(205)Tl hyperfine interactions permit accurate
      simulations of the EPR spectra and the extraction of specific rates of
      hole/electron transfer. The (203)Tl/(205)Tl hyperfine clock strategy is applied
      to a series of seven porphyrin dyads. All of the dyads are joined at a meso
      position of the porphyrin macrocycle via linkers of a range of lengths and
      composition (diphenylethyne, diphenylbutadiyne, and (p-phenylene)(n), where n = 1
      4); substituents such as mesityl at the nonlinking meso positions are employed to
      provide organic solubility. The hole/electron-transfer time constants are in the
      hundreds of picoseconds to sub-10 ns regime, depending on the specific porphyrin
      and/or linker. Density functional theory calculations on the constituents of the
      dyads are consistent with the view that the relative energies of the porphyrin
      versus linker highest occupied molecular orbitals strongly influence the
      hole/electron-transfer rates. Variable-temperature EPR studies further
      demonstrate that the hole/electron-transfer process is at best weakly activated
      (12-15 kJ mol(-1)) at room temperature and somewhat below. At lower temperatures,
      the process is essentially activationless. The weak activation is attributed to
      restricted torsional motions of the phenyl rings of the linker. Collectively, the
      studies provide the physical basis for the rational design of multicomponent
      architectures for efficient hole/electron transfer.

PMID- 20690678
TI  - Shotgun proteomic analysis of yeast-elicited California poppy (Eschscholzia
      californica) suspension cultures producing enhanced levels of benzophenanthridine
      alkaloids.
AB  - The California poppy, Eschscholzia californica, produces benzophenanthridine
      alkaloids (BPAs), an important class of biologically active compounds. Cell
      cultures of E. californica were investigated as an alternative and scalable
      method for producing these valuable compounds; treatment with yeast extract
      increased production from low levels to 23 mg/g dry weight (DW) of BPAs. A
      shotgun proteomic analysis of E. californica cell cultures was undertaken to
      explore changes in metabolism associated with enhanced BPA production. We
      implemented differential centrifugation and then shotgun proteomics based on
      nanoliquid chromatography/mass spectrometry (nano-LC-MS/MS) for peptide
      separation and analysis. A unigene database available for E. californica was
      translated and utilized for protein identification. Approximately 646 proteins
      (3% false discovery rate at the protein level) were identified. Differentially
      abundant proteins observed with elicitation included enzymes involved in (S)
      adenosyl methionine (SAM) biosynthesis and BPA biosynthesis. These results
      demonstrate (1) the identification of proteins from a medicinal plant using
      shotgun proteomics combined with a well-annotated, translated unigene database
      and (2) the potential utility of proteomics for exploring changes in metabolism
      associated with enhanced secondary metabolite production.

PMID- 20690679
TI  - Structural and biochemical determinants of ligand binding by the c-di-GMP
      riboswitch .
AB  - The bacterial second messenger c-di-GMP is used in many species to control
      essential processes that allow the organism to adapt to its environment. The c-di
      GMP riboswitch (GEMM) is an important downstream target in this signaling pathway
      and alters gene expression in response to changing concentrations of c-di-GMP.
      The riboswitch selectively recognizes its second messenger ligand primarily
      through contacts with two critical nucleotides. However, these two nucleotides
      are not the most highly conserved residues within the riboswitch sequence.
      Instead, nucleotides that stack with c-di-GMP and that form tertiary RNA contacts
      are the most invariant. Biochemical and structural evidence reveals that the most
      common natural variants are able to make alternative pairing interactions with
      both guanine bases of the ligand. Additionally, a high-resolution (2.3 A) crystal
      structure of the native complex reveals that a single metal coordinates the c-di
      GMP backbone. Evidence is also provided that after transcription of the first
      nucleotide on the 3'-side of the P1 helix, which is predicted to be the molecular
      switch, the aptamer is functional for ligand binding. Although large energetic
      effects occur when several residues in the RNA are altered, mutations at the most
      conserved positions, rather than at positions that base pair with c-di-GMP, have
      the most detrimental effects on binding. Many mutants retain sufficient c-di-GMP
      affinity for the RNA to remain biologically relevant, which suggests that this
      motif is quite resilient to mutation.

PMID- 20690681
TI  - Development of flexible LEO-resistant PI films for space applications using a
      self-healing mechanism by surface-directed phase separation of block copolymers.
AB  - Polimide-block-polydimethylsiloxane (PI-b-PDMS) block copolymers have been
      synthesized from commercially available amino-terminated polysiloxanes with
      different molecular weights, for use as polymeric materials resistant to the low
      earth orbit (LEO) space environment. A structural optimization with respect to
      maximum environmental protection has been performed by varying the PDMS block
      length as well as the architecture of the block copolymers spanning from
      multiblock to triblock and star-shaped morphologies. The synthesized polymers and
      casted films show good mechanical and thermal performance. For block copolymers
      with a load of 2% PDMS (in the case of the multiblock copolymers), a complete
      surface coverage of the PDMS has been found. It has been shown that the transfer
      of the surface enriched PDMS layer into a thin silica layer after atomic oxygen
      (AO) exposure results in a drastic decrease in AO erosion rate. The silica layer
      protects the underlying material from oxygen initiated erosion resulting in a
      drastic decrease of surface roughness. This phenomena is observable for loads as
      small as 6 wt % PDMS.

PMID- 20690680
TI  - Anthrax toxin receptor 1/tumor endothelial marker 8: mutation of conserved
      inserted domain residues overrides cytosolic control of protective antigen
      binding.
AB  - Anthrax toxin receptor 1 (ANTXR1)/tumor endothelial marker 8 (TEM8) is one of two
      known proteinaceous cell surface anthrax toxin receptors. A metal ion dependent
      adhesion site (MIDAS) present in the integrin-like inserted (I) domain of ANTXR1
      mediates the binding of the anthrax toxin subunit, protective antigen (PA). Here
      we provide evidence that single point mutations in the I domain can override
      regulation of ANTXR1 ligand-binding activity mediated by intracellular signals. A
      previously reported MIDAS mutant of ANTXR1 (T118A) was found to retain normal
      metal ion binding and secondary structure but failed to bind PA, consistent with
      a locked inactive state. Conversely, mutation of a conserved I domain
      phenylalanine residue to a tryptophan (F205W) increased the proportion of cell
      surface ANTXR1 that bound PA, consistent with a locked active state.
      Interestingly, the K(D) and total amount of PA bound by the isolated ANTXR1 I
      domain were not affected by the F205W mutation, indicating that ANTXR1 is
      preferentially found in the active state in the absence of inside-out signaling.
      Circular dichroism (CD) spectroscopy and (1)H-(15)N heteronuclear single-quantum
      coherence (HSQC) nuclear magnetic resonance (NMR) revealed that structural
      changes between T118A, F205W, and WT I domains were minor despite a greater than
      10(3)-fold difference in their abilities to bind toxin. Regulation of toxin
      binding has important implications for the design of toxin inhibitors and for the
      targeting of ANTXR1 for antitumor therapies.

PMID- 20690682
TI  - Density functional theory interpretation of the 1H photo-chemically induced
      dynamic nuclear polarization enhancements characterizing photoreduced
      polyazaaromatic Ru(II) coordination complexes.
AB  - The unprotonated and protonated monoreduced forms of the polyazaaromatic Ru(II)
      coordination complexes [Ru(tap)(3)](2+) and [Ru(tap)(2)(phen)](2+) (tap = 1,4,5,8
      tetraazaphenanthrene ; phen = 1,10-phenanthroline), that is, [Ru(tap)(3)](*+),
      [Ru(tap)(2)(phen)](*+), [Ru(tap)(2)(tap-H)](*2+), and [Ru(tap)(tap
      H)(phen)](*2+), were studied by Density Functional Theory (DFT). The electron
      spin density of these radical cations, the isotropic Fermi-contact, and the
      anisotropic dipolar contributions to the hyperfine coupling constants of the H
      nuclei were calculated in vacuo and using a continuum model for water solvation.
      For [Ru(tap)(2)(phen)](*+), as well as for its protonated form, the DFT results
      show that the unpaired electron is not localized on the phen ligand. For both
      [Ru(tap)(3)](*+) and [Ru(tap)(2)(phen)](*+), they reveal high electron spin
      density in the vicinity of tap H-2 and tap H-7 (the H atoms in the ortho position
      of the tap non-chelating N atoms). These results are in full agreement with
      recent steady-state (1)H photo-Chemically Induced Dynamic Nuclear Polarization
      (photo-CIDNP) measurements. The DFT calculations performed for the protonated
      species also predict major (1)H photo-CIDNP enhancements at these positions.
      Interestingly, they indicate significantly different polarization for tap H-9,10,
      suggesting that the occurrence of a photoinduced electron transfer with
      protonation of the reduced species might be detected by high-precision photo
      CIDNP experiments.

PMID- 20690683
TI  - Hexanickel enediolate cluster generated in an acireductone dioxygenase model
      reaction.
AB  - A nickel(II) enediolate cluster (2) forms upon treatment of [(6
      Ph(2)TPA)Ni(PhC(O)C(OH)C(O)Ph)]ClO(4) (1) with Me(4)NOH x 5 H(2)O in CH(3)CN.
      Crystallographic studies of 2 revealed a hexanuclear structure of S(6) symmetry
      with a formula of {[Ni(PhC(O)C(O)C(O)Ph)(CH(3)OH)] x 1.33 CH(3)OH}(6). Because
      isolation of bulk amounts of 2 from the reaction involving 1 proved impossible, a
      solvation analogue of 2 (labeled 5) was generated from admixture of Ni(ClO(4))(2)
      x 6 H(2)O, 2-hydroxy-1,3-diphenylpropane-1,3-dione, and Me(4)NOH x 5 H(2)O in
      CH(3)OH/CH(3)CN. Complex 5 is formulated as {[Ni(PhC(O)C(O)C(O)Ph)(H(2)O)] x
      H(2)O x 0.25 CH(3)CN}(6) based on elemental analysis, a molecular weight
      determination, UV-vis, and a magnetic moment measurement. Treatment of 5 with
      O(2) and 6-Ph(2)TPA (6 equiv) results in the formation of CO and [(6
      Ph(2)TPA)Ni(O(2)CPh)(2)(H(2)O)] (3), the latter of which was isolated in 69%
      yield. The level of (18)O incorporation in this reaction matches that for a
      reaction wherein 2 is generated from 1. These results provide evidence that a
      nickel(II) enediolate cluster is the O(2) reactive species in a previously
      reported model reaction for nickel(II)-containing acireductone dioxygenase.

PMID- 20690684
TI  - Chemistry of molybdaboranes: synthesis, structures, and characterization of a new
      class of open-cage dimolybdaheteroborane clusters.
AB  - Reaction of [Cp*MoCl(4)], 1 (Cp* = eta(5)-C(5)Me(5)), with [LiBH(4).thf] in
      toluene at -70 degrees C, followed by pyrolysis with excess dichalcogenides RE-ER
      (R = Ph, CH(2)Ph, 2,6-((t)Bu)(2)-C(6)H(2)OH, (CH(3))(3)C = (t)Bu); E = S, Se)
      yielded a new class of hybrid clusters, 3-8: (3, [(Cp*Mo)(2)(mu-eta(1)
      SPh)(2)(mu(3)-S)(H(2)BSPh)]; 4, [(Cp*Mo)(2)B(5)H(8)(SPh)]; 5,
      [(Cp*Mo)(2)B(5)H(8)(SePh)]; 6, [(Cp*Mo)(2)B(2)S(2)H(2)(mu-eta(1)-S)]; 7,
      [(Cp*Mo)(2)B(2)H(5)(BSR)(2)(mu-eta(1)-SR)], (R = 2,6-((t)Bu)(2)-C(6)H(2)OH); and
      8, [(Cp*Mo)(2)B(2)H(5)(BSePh)(2)(mu-eta(1)-SePh)]. Compounds 3-8 have been
      isolated in modest yields as green or brown crystalline solids. In parallel with
      3-8, [(Cp*Mo)(2)B(5)H(9)] was isolated as a major product in all cases. The
      isolation and structural characterization of compounds 3 and 6-8 provided the
      first direct evidence of the existence of [(Cp*Mo)(2)B(4)H(8)], 2, an
      intermediate in the formation of [(Cp*Mo)(2)B(5)H(9)]. These new compounds have
      been characterized in solution by mass spectrometry, (1)H, (11)B, (13)C NMR, and
      IR spectroscopy, and elemental analysis. The structural types were unequivocally
      established by X-ray crystallographic analysis of compounds 3-8.

PMID- 20690685
TI  - Bis[3-(5-nitroimino-1,2,4-triazolate)]-based energetic salts: synthesis and
      promising properties of a new family of high-density insensitive materials.
AB  - Bis[3-(5-nitroimino-1,2,4-triazolate)]-based energetic salts were synthesized in
      a simple, straightforward manner. They exhibit low solubility in available
      solvents, high hydrolytic stability, excellent thermal stability, high density,
      positive heat of formation, low shock sensitivity, and excellent detonation
      properties. The physical and energetic properties of some salts are similar and
      even superior to those of RDX.

PMID- 20690686
TI  - Synthesis, in vitro activity, and three-dimensional quantitative structure
      activity relationship of novel hydrazine inhibitors of human vascular adhesion
      protein-1.
AB  - Vascular adhesion protein-1 (VAP-1) belongs to the semicarbazide-sensitive amine
      oxidases (SSAOs) that convert amines into aldehydes. SSAOs are distinct from the
      mammalian monoamine oxidases (MAOs), but their substrate specificities are partly
      overlapping. VAP-1 has been proposed as a target for anti-inflammatory drug
      therapy because of its role in leukocyte adhesion to endothelium. Here, we
      describe the synthesis and in vitro activities of novel series of VAP-1 selective
      inhibitors. In addition, the molecular dynamics simulations performed for VAP-1
      reveal that the movements of Met211, Ser496, and especially Leu469 can enlarge
      the ligand-binding pocket, allowing larger ligands than those seen in the crystal
      structures to bind. Combining the data from molecular dynamics simulations,
      docking, and in vitro measurements, the three-dimensional quantitative structure
      activity relationship (3D QSAR) models for VAP-1 (q(2)(LOO): 0.636; r(2): 0.828)
      and MAOs (q(2)(LOO): 0.749, r(2): 0.840) were built and employed in the
      development of selective VAP-1 inhibitors.

PMID- 20690687
TI  - Synthesis of indolequinones from bromoquinones and enamines mediated by
      Cu(OAc)2.H2O.
AB  - A Cu(II)-mediated synthesis of indolequinones from the corresponding
      bromoquinones and enamines is reported. The key oxidative cyclization proceeds in
      good yield for a broad range of substrates and can be performed on a multigram
      scale, allowing access to biologically interesting structures.

PMID- 20690688
TI  - Experimental characterization and modelization of ion exchange kinetics for a
      carboxylic resin in infinite solution volume conditions. Application to
      monovalent-trivalent cations exchange.
AB  - This study is devoted to the characterization of ion exchange inside a
      microsphere of carboxylic resin. It aims at describing the kinetics of this
      exchange reaction which is known to be controlled by interdiffusion in the
      particle. The fractional attainment of equilibrium function of time depends on
      the concentration of the cations in the resin which can be modelized by the
      Nernst-Planck equation. A powerful approach for the numerical resolution of this
      equation is introduced in this paper. This modeling is based on the work of
      Helfferich but involves an implicit numerical scheme which reduces the
      computational cost. Knowing the diffusion coefficients of the cations in the
      resin and the radius of the spherical exchanger, the kinetics can be hence
      completely determined. When those diffusion parameters are missing, they can be
      deduced by fitting experimental data of fractional attainment of equilibrium. An
      efficient optimization tool coupled with the implicit resolution has been
      developed for this purpose. A monovalent/trivalent cation exchange had been
      experimentally characterized for a carboxylic resin. Diffusion coefficients and
      concentration profiles in the resin were then deduced through this new model.

PMID- 20690689
TI  - Stereoselective syntheses of trisubstituted olefins via platinum catalysis: alpha
      silylenones with geometrical complementarity.
AB  - The stereoselective syntheses of alpha-silylenones using catalytic PtCl(2) are
      reported. Via alkyne activation, alpha-hydroxypropargylsilanes are converted to
      (Z)-silylenones through a highly selective silicon migration. The complementary
      (E)-silylenones are accessed by a regioselective hydrosilylation of the ynone
      precursor. The synthetic utility of these compounds is demonstrated in cross
      coupling reactions, highlighting the potential of these protocols for the
      syntheses of geometrically defined trisubstituted olefins.

PMID- 20690690
TI  - Molecular dynamics simulations shed light on the enthalpic and entropic driving
      forces that govern the sequence specific recognition between netropsin and DNA.
AB  - With the aim to gain a better understanding of the various driving forces that
      govern sequence specific DNA minor groove binding, we performed a thermodynamic
      analysis of netropsin binding to an AT-containing and to a set of six mixed AT/GC
      containing binding sequences in the DNA minor groove. The relative binding free
      energies obtained using molecular dynamics simulations and free energy
      calculations show significant variations with the binding sequence. While the
      introduction of a GC base pair in the middle or close to the middle of the
      binding site is unfavorable for netropsin binding, a GC base pair at the end of
      the binding site appears to have no negative influence on the binding. The
      results of the structural and energetic analyses of the netropsin-DNA complexes
      reveal that the differences in the calculated binding affinities cannot be
      explained solely in terms of netropsin-DNA hydrogen-bonding or interaction
      energies. In addition, solvation effects and entropic contributions to the
      relative binding free energy provide a more complete picture of the various
      factors determining binding. Analysis of the relative binding entropy indicates
      that its magnitude is highly sequence-dependent, with the ratio
      |TDeltaDeltaS|/|DeltaDeltaH| ranging from 0.07 for the AAAGA to 1.7 for the AAGAG
      binding sequence, respectively.

PMID- 20690691
TI  - Room temperature acylketene formation? 1,3-Dioxin-4-ones via silver(I) activation
      of phenylthioacetoacetate in the presence of ketones.
AB  - Silver(I) activation of thioacetoacetates in the presence of ketones produces 1,3
      dioxin-4-ones. Mechanistic studies addressing the intermediacy of an acylketene
      intermediate are described.

PMID- 20690692
TI  - Molecular dynamics study of a heteroditopic-calix[4]diquinone-assisted transfer
      of KCl and dopamine through a water-chloroform liquid-liquid interface.
AB  - The ability of two heteroditopic calix[4]diquinone receptors to transport a KCl
      ion-pair and a dopamine zwitterion through a water-chloroform interface was
      investigated via molecular dynamics (MD) simulations. Gas-phase conformational
      analysis has been carried on KCl and dopamine receptor binding associations and
      the lowest energy structures found in both cases show that the recognition of KCl
      and dopamine zwitterion occurs through multiple and cooperative N-H...anion and
      O...cation bonding interactions, with the receptor adopting equivalent folded
      conformations stabilized by pi-stacking interactions. The unconstrained MD
      simulations performed on KCl and dopamine complexes inserted in either the
      chloroform or water phase revealed that receptors are preferentially located at
      the interface with the hydrophobic tert-butyl groups of the calix[4]diquinone
      moiety immersed in the chloroform bulk while the polar anion binding cavity is
      directed toward the water phase. When the KCl complex is placed in chloroform,
      the release of the ion-pair occurs only after the first contact with the water
      interface, being a nonsimultaneous event, with the chloride anion leaving the
      receptor before the potassium cation. The dopamine, via the -NH(3)(+) binding
      entity, remains bound to the receptor during the entire time of the MD simulation
      (10 ns). In contrast, when both complexes were inserted in the water bulk, the
      full release of KCl and dopamine are fast events. The potentials of mean force
      (PMFs), associated with the migration of the complexes from chloroform to water
      through the interface, were calculated from steered molecular dynamics (SMD)
      simulations. The PMFs for the free KCl and zwitterionic dopamine migrations were
      also obtained for comparison purposes. The transport of KCl from water to
      chloroform (the reverse path) mediated by the receptor has a free energy barrier
      estimated in 6.50 kcal mol(-1), which is 3.0 kcal mol(-1) smaller than that found
      for the free KCl. The transport of dopamine complex along the reverse path is
      characterized by downhill energy profile, with a small free energy barrier of
      6.56 kcal mol(-1).

PMID- 20690693
TI  - Determination of phase transition temperatures for atomistic models of lipids
      from temperature-dependent stripe domain growth kinetics.
AB  - Many lipid bilayers undergo a reversible order-disorder transition between the
      gel and liquid crystalline (LC) phases at a main phase transition temperature
      T(m) that is an important characteristic property of the lipid. Although T(m)
      should serve as a useful standard for validation and calibration of simulation
      models of lipid bilayers, its evaluation within simulations is difficult due to
      the slow kinetics of the gel-LC transition, especially near T(m). A stripe growth
      strategy for calculating T(m), which aims to bypass the slowest steps in this
      transition, has been applied to dipalmitoylphosphatidylcholine and
      distearoylphosphatidylcholine bilayers represented with a commonly used united
      atom force field. The strategy consists of initial preparation of a bilayer
      containing gel and LC domains arranged as parallel stripes, observation of the
      direction and rate of domain growth over a range of temperatures, and fitting
      rates to an Arrhenius-like equation for their temperature dependence that crosses
      zero at T(m). Calculated T(m)'s for both lipids are 5-6 degrees lower than their
      experimental values, in much closer agreement with experiment than suggested by
      recent simulations that simulate heating and cooling of bilayer patches. The
      stripe growth method also yields rates of phase front propagation that are in
      order-of-magnitude agreement with experimental estimates, as well as insight into
      glycerol backbone disordering at the LC-gel interface.

PMID- 20690694
TI  - Adsorption of an antimicrobial peptide on self-assembled monolayers by molecular
      dynamics simulation.
AB  - We present results of molecular dynamics simulations of the interaction of a 48
      amino acid peptide, carnobacteriocin B2, with model hydrophobic, anionic, and
      cationic self-assembled monolayers (SAMs). The model monolayers were formed by
      placing alkanethiols, HS-(CH(2))(10)-X, where the terminal functional group X was
      chosen to be CH(3), COO(-), or NH(3)(+). The carboxylate and amine groups were
      modeled as either fully charged or partially charged. Furthermore, simulations
      are presented for nanopatterned SAMs consisting of parallel stripes of
      hydrophobic/anionic and anionic/cationic SAMs. These simulations help elucidate
      the mechanisms of interaction of the peptide with model surfaces that emulate the
      chemical heterogeneity of lipid bilayer membranes or peptide nanoarrays. The
      simulation results depict how the nanoscale chemical heterogeneity of surfaces
      can simultaneously alter the peptide's interaction with the surface and its
      secondary structure. Hydrophobic interactions result in the strongest adsorption
      of the peptide to the monolayer, simultaneously maintaining the structural
      integrity of the peptide. Electrostatic interactions, on the other hand, tend to
      enhance the solvation of the peptide, thereby causing radical changes in the
      secondary structure.

PMID- 20690695
TI  - In silico prediction of the melting points of ionic liquids from thermodynamic
      considerations: a case study on 67 salts with a melting point range of 337
      degrees C.
AB  - The melting points (T(fus)) of crystalline ionic liquids are calculated from the
      ratio of the fusion enthalpy and entropy at the melting point where solid and
      liquid phases are in chemical equilibrium (DeltaG(T) = 0), and therefore, T(fus)
      = Delta(fus)H(T)/Delta(fus)S(T) (if T = T(fus)). We specify two variants of this
      method that have no need for experimental input or tedious simulations but rely
      on simple calculations feasible with standard quantum chemical program codes and
      may further be augmented by COSMO-RS. Only single ions are used as input, making
      the demanding calculation of ion pairs superfluous. The fusion enthalpy is
      obtained by the principles of volume-based thermodynamics (ion volumes as the
      major contributor), which may additionally be augmented by COSMO-RS interaction
      enthalpies for increased accuracy. The calculation of the fusion entropy largely
      relies on a procedure originally developed for neutral organic molecules that was
      extended to molecular ionic compounds. Its contributors are the site symmetry
      sigma and the number of torsion angles tau, which are both determined
      individually for the cation and the anion and are included as their geometric
      mean. The two methods were tested on several sets of ionic liquids (ILs) and a
      combination of all sets (67 ILs) that span an experimental melting temperature
      range of 337 degrees C. The average error of the simpler, volume-based model
      (only ion volumes, sigma, and tau as input) is 36.4 degrees C and that of the
      augmented method (using ion volumes, sigma, tau, and COSMO-RS output) is 24.5
      degrees C.

PMID- 20690696
TI  - Self-assembly and host-guest interaction of metallomacrocycles using fluorescent
      dipyrazole linker with dimetallic clips.
AB  - By employing diimine ligands coordinated dimetallic clips
      ([(bpy)2Pd2(NO3)2](NO3)2 or [(phen)2Pd2(NO3)2](NO3)2, where bpy = 2,2'
      bipyridine, phen = 1,10-phenanthroline) as the corner and anthracene-,
      naphthalene-, and benzene-based dipyrazolate dianions as the linker, a series of
      positively charged metallomacrocycles ([M4L2]4+ or [M8L4]8+) have been
      synthesized through a directed self-assembly method in aqueous solution. Every
      macrocycle has a cavity to bind solvent molecules or anions. The structures were
      characterized by elemental analysis, 1H and 13C NMR, electrospray ionization mass
      spectrometry, and single crystal X-ray diffraction analysis for compound 1 x 4
      PF6(-) (1 = {[(bpy)Pd]4L(1)2}4+), 3 x 4 PF6(-) x 8 CH3CN x H2O (3 =
      {[(bpy)Pd]4L(2)2}4+), and 7 x 4 PF6(-) x 6 H2O (7 = {[(bpy)Pd]4L(5)2}4+). The 1:1
      host-guest complexation for anthracene-based dipyrazolate-bridged macrocycles
      with aromatic guests was investigated via UV-vis and fluorescent titration.

PMID- 20690697
TI  - Melting of a beta-hairpin peptide using isotope-edited 2D IR spectroscopy and
      simulations.
AB  - Isotope-edited two-dimensional infrared spectroscopy has been used to
      characterize the conformational heterogeneity of the beta-hairpin peptide TrpZip2
      (TZ2) across its thermal unfolding transition. Four isotopologues were
      synthesized to probe hydrogen bonding and solvent exposure of the beta-turn (K8),
      the N-terminus (S1), and the midstrand region (T10 and T3T10). Isotope-shifts, 2D
      lineshapes, and other spectral changes to the amide I 2D IR spectra of labeled
      TZ2 isotopologues were observed as a function of temperature. Data were
      interpreted on the basis of structure-based spectroscopic modeling of conformers
      obtained from extensive molecular dynamics simulations. The K8 spectra reveal two
      unique turn geometries, the type I' beta-turn observed in the NMR structure, and
      a less populated disordered or bulged loop. The data indicate that structures at
      low temperature resemble the folded NMR structure with typical cross-strand
      hydrogen bonds, although with a subpopulation of misformed turns. As the
      temperature is raised from 25 to 85 degrees C, the fraction of population with a
      type I' turn increases, but the termini also fray. Hydrogen bonding contacts in
      the midstrand region remain at all temperatures although with increasing thermal
      disorder. Our data show no evidence of an extended chain or random coil state for
      the TZ2 peptide at any temperature. The methods demonstrated here offer an
      approach to characterizing conformational variation within the folded or unfolded
      states of proteins and peptides.

PMID- 20690698
TI  - Catalytic asymmetric aza-Morita-Baylis-Hillman reaction of methyl acrylate: role
      of a bifunctional La(O-iPr)3/linked-BINOL complex.
AB  - The catalytic asymmetric aza-Morita-Baylis-Hillman reaction using unactivated
      methyl acrylate is described. A simple Lewis acidic metal catalyst, such as
      La(OTf)(3), was not suitable for the reaction, but rare earth metal
      alkoxide/linked-BINOL complexes possessing bifunctional Lewis acid and Bronsted
      base properties efficiently promoted the reaction in combination with an achiral
      nucleophilic organocatalyst. The combined use of a La(O-iPr)(3)/(S,S)-TMS-linked
      BINOL complex with a catalytic amount of DABCO promoted the aza-Morita-Baylis
      Hillman reaction of a broad range of N-diphenylphosphinoyl imines. Products from
      aryl, heteroaryl, and alkenyl imines were obtained in 67-99% yield and 81-95% ee.
      It is noteworthy that isomerizable alkyl imines could be employed as well, giving
      products in 78-89% yield and 94-98% ee. Initial rate kinetic studies as well as
      kinetic isotope effect experiments using alpha-deuterio-methyl acrylate support
      the importance of both the nucleophilicity of La-enolate and the Bronsted
      basicity of a La-catalyst for promoting the reaction.

PMID- 20690699
TI  - Microsecond time scale mobility in a solid protein as studied by the 15N R(1rho)
      site-specific NMR relaxation rates.
AB  - For the first time, we have demonstrated the site-resolved measurement of
      reliable (i.e., free of interfering effects) (15)N R(1rho) relaxation rates from
      a solid protein to extract dynamic information on the microsecond time scale.
      (15)N R(1rho) NMR relaxation rates were measured as a function of the residue
      number in a (15)N,(2)H-enriched (with 10-20% back-exchanged protons at labile
      sites) microcrystalline SH3 domain of chicken alpha-spectrin. The experiments
      were performed at different temperatures and at different spin-lock frequencies,
      which were realized by on- and off-resonance spin-lock irradiation. The results
      obtained indicate that the interfering spin-spin contribution to the R(1rho) rate
      in a perdeuterated protein is negligible even at low spin-lock fields, in
      contrast to the case for normal protonated samples. Through correlation plots,
      the R(1rho) rates were compared with previous data for the same protein
      characterizing different kinds of internal mobility.

PMID- 20690700
TI  - Diastereoselective one-pot tandem synthesis of 3-substituted isoindolinones: a
      mechanistic investigation.
AB  - The mechanism of a base-catalyzed one-pot reaction of 2-cyanobenzaldehyde and
      primary nitroalkanes, to produce 3-substituted isoindolinones, has been
      investigated. A route starting with a nitroaldol (Henry) reaction, followed by a
      subsequent cyclization and rearrangement, was supported by intermediate analogue
      synthesis and DFT calculations. Direct diastereoselective crystallization from
      the reaction mixture was also achieved and studied for a number of substrates.
      Furthermore, the 3-substituted isoindolinones are an interesting group of
      compounds, both present important natural products, as well as being precursors
      to other valuable building blocks.

PMID- 20690701
TI  - Defect-mediated trafficking across cell membranes: insights from in silico
      modeling.

PMID- 20690702
TI  - Structural and functional characterization of the ga-substituted ferredoxin from
      Synechocystis sp. PCC6803, a mimic of the native protein.
AB  - In photosynthetic organisms, ferredoxin (Fd) interacts with many proteins, acting
      as a shuttle for electrons from Photosystem I to a group of enzymes involved in
      NADP(+) reduction, sulfur and nitrogen assimilation, and the regulation of carbon
      assimilation. The study of the dynamic interactions between ferredoxin and these
      enzymes by nuclear magnetic resonance is severely hindered by the paramagnetic
      [2Fe-2S] cluster of a ferredoxin. To establish whether ferredoxin in which the
      cluster has been replaced by Ga is a suitable diamagnetic mimic, the solution
      structure of Synechocystis Ga-substituted ferredoxin has been determined and
      compared with the structure of the native protein. The ensemble of 10 structures
      with the lowest energies has an average root-mean-square deviation of 0.30 +/-
      0.05 A for backbone atoms and 0.65 +/- 0.04 A for all heavy atoms. Comparison of
      the NMR structure of GaFd with the crystal structure of the native Fd indicates
      that the general structural fold found for the native, iron-containing ferredoxin
      is conserved in GaFd. The ferredoxin contains a single gallium and no inorganic
      sulfide. The distortion of the metal binding loop caused by the single gallium
      substitution is small. The binding site on Fd for binding ferredoxin:NADP(+)
      reductase in solution, determined using GaFd, includes the metal binding loop and
      its surroundings, consistent with the crystal structures of related complexes.
      The results provide a structural justification for the use of the gallium
      substituted analogue in interaction studies.

PMID- 20690703
TI  - Four-dimensional orthogonal electrophoresis system for screening protein
      complexes and protein-protein interactions combined with mass spectrometry.
AB  - Most current approaches for purification and identification of protein complexes
      adopt affinity purifications combined with mass spectrometry, such as co
      immunoprecipitation and tandem affinity purification. Herein, we propose a new
      approach, termed as the four-dimensional orthogonal electrophoresis (4-DE)
      system, to find and analyze the cytoplasmic protein complexes. 4-DE system is
      composed of two parts: nondenaturing part (Part I) and denaturing part (Part II).
      Through Part I and decision procedure separations, six protein complex candidates
      20S core particle of proteasome (CP), hemoglobin (Hb, alpha2beta2), Hb
      (alpha2delta2), peroxiredoxin-2 (PRDX2), carbonic anhydrase-1 (CAH1), and heat
      shock protein 60 (HSP60) were separated. CP, Hb (alpha2beta2), PRDX2, and HSP60
      with different MWs and pI's were chosen for Part II proteomic analysis. The
      results indicate that 4-DE is not only suitable for studying protein complexes
      and protein-protein interactions as well as structural proteomics from complex
      biological samples, but can also be easy to separate and concentrate intact
      protein complexes from dilute complex samples.

PMID- 20690704
TI  - Thermosensitive liposomes modified with poly(N-isopropylacrylamide-co
      propylacrylic acid) copolymers for triggered release of doxorubicin.
AB  - A novel polymer-modified thermosensitive liposome (pTSL) was developed for the
      delivery of Doxorubicin (DOX) for cancer therapy. Copolymers containing
      temperature-responsive N-isopropylacrylamide (NIPAAm) and pH-responsive
      propylacrylic acid (PAA) were synthesized via reversible addition-fragmentation
      chain transfer (RAFT) polymerization, yielding copolymers with dual
      pH/temperature-dependent phase transition properties. When attached to liposomes,
      these copolymers were membrane-disruptive in a pH/temperature-dependent manner.
      pTSL demonstrated enhanced release profile and significantly lower thermal dose
      threshold when compared to traditional thermosensitive formulations and were
      stable in serum with minimal drug leakage over time. These liposomes thus have
      the potential to dramatically reduce the risk of damage to healthy tissues that
      is normally associated with liposomal cancer therapy.

PMID- 20690705
TI  - Organo-catalyzed ring opening polymerization of a 1,4-dioxane-2,5-dione deriving
      from glutamic acid.
AB  - The (3S)-[(benzyloxycarbonyl)ethyl]-1,4-dioxan-2,5-dione (BED) was prepared in
      four steps starting from glutamic acid and bromoacetyl bromide. According to X
      ray diffraction analysis, the pendant functional group is located in equatorial
      position and points away from the six-membered ring. The organo-catalyzed ring
      opening polymerization of BED was promoted with 4-dimethylaminopyridine (DMAP)
      and the combination of thiourea TU(Cy) and (-)-sparteine. PolyBED samples of
      number-average molar mass M(n) up to 36000 and narrow polydispersity (M(w)/M(n) <
      1.25) were thereby prepared in a controlled manner under mild conditions
      (dichloromethane solution, 30 degrees C), as substantiated by size-exclusion
      chromatography, matrix-assisted laser desorption ionization time-of-flight-mass
      spectrometry (MALDI-TOF-MS) and nuclear magnetic resonance (NMR) spectroscopy.
      The pendant functional group does not interfere with the polymerization and BED
      was even found to be slightly more reactive than lactide. Despite the strongly
      dissymmetric substitution pattern of the 1,4-dioxan-2,5-dione core, the ensuing
      polyBED polymers present a random distribution of glycolic
      [(benzyloxycarbonyl)ethyl]glycolic (gly glu) units, as supported by a (1)H-(13)C
      HMBC 2D NMR experiment. The preparation of 1:1 adducts with n-pentanol confirmed
      that ring-opening of BED occurs almost indifferently on either of the endocyclic
      ester groups. Poly(alpha-hydroxyacids) featuring pendant carboxylic acids were
      finally obtained by acetylation of the terminal OH groups followed by
      hydrogenolysis.

PMID- 20690706
TI  - Synthesis and organocatalytic ring-opening polymerization of cyclic esters
      derived from l-malic acid.
AB  - The synthesis of 3-(S)-[(benzyloxycarbonyl)methyl]-1,4-dioxane-2,5-dione (BMD)
      and 3,6-(S)-[di(benzyloxycarbonyl)methyl]-1,4-dioxane-2,5-dione (malide) from
      commercially available l-malic acid is reported. Ring-opening polymerization
      (ROP) studies of BMD are reported showing that the controlled ROP of this monomer
      is possible in the absence of transesterification side reactions, despite the
      presence of side-chain esters, using 1-(3,5-bis(trifluoromethyl)phenyl)-3
      cyclohexylthiourea and (-)-sparteine to catalyze the polymerization. The ROP of
      malide with this system was ineffective. Investigation of the effect of
      initiating species revealed that the electronic nature of the alcohol had a
      greater effect on the ultimate molecular weight and hence initiator efficiency
      than steric considerations. Deprotection of the resultant poly(BMD) using H(2)
      and Pd/C resulted in hydrophilic poly(glycolic-co-malic acid)s (PGMAs) that were
      able to undergo autocatalytic degradation in dilute H(2)O solution such that
      complete degradation was observed within 6 days.

PMID- 20690707
TI  - Investigation of pore size effect on chondrogenic differentiation of adipose stem
      cells using a pore size gradient scaffold.
AB  - In this study, polycaprolactone (PCL) cylindrical scaffolds with gradually
      increasing pore size along the longitudinal direction were fabricated by the
      centrifugation and thermal fibril-bonding process. The fabricated PCL scaffold
      showed a gradual increasing pore size (from approximately 90 to approximately 400
      microm) and porosity (from approximately 80 to approximately 97%) along the
      cylindrical axis. The pore size gradient PCL scaffold was used to investigate the
      effect of pore size on the chondrogenic differentiation of adipose stem cells
      (ASCs). From the in vitro culture of ASCs, it was observed that the scaffold
      section having a pore size range of 370-400 microm provided a more favorable
      environment for chondrogenic differentiation than other pore size groups. The
      pore size gradient scaffolds can be a good tool for the systematic study of
      determining optimum pore size ranges for a variety of stem cell differentiation
      to a specific cell type.

PMID- 20690708
TI  - Immobilization of human mesenchymal stem cells within RGD-grafted alginate
      microspheres and assessment of their angiogenic potential.
AB  - In this work, human mesenchymal stem cells (hMSC) immobilized in RGD-coupled
      alginate microspheres, with a binary composition of high and low molecular weight
      alginate, were investigated. Cells immobilized within RGD-alginate microspheres
      (during 21 days) showed metabolic activity, with an overall viability higher than
      90%, short cell extensions, and, when induced, they were able to differentiate
      into the osteogenic lineage. In osteogenic conditions (comparing to basal
      conditions), immobilized cells presented alkaline phosphatase (ALP) activity and
      an upregulation of ALP, collagen type I, and Runx 2 expression. Moreover,
      mineralization was also detected in immobilized cells under osteogenic stimulus.
      In addition, it was demonstrated for the first time that MSCs immobilized in this
      3D matrix were able to enhance the ability of neighboring endothelial cells to
      form tubelike structures. Overall, these findings represent a step forward in the
      development of injectable stem cell carriers for bone tissue engineering.

PMID- 20690709
TI  - Polysaccharide pharmacokinetics: amphotericin B arabinogalactan conjugate-a drug
      delivery system or a new pharmaceutical entity?
AB  - Conjugation of poorly soluble drugs to polysaccharides affects their solubility,
      pharmacokinetics (PK), and pharmacodynamics. The need for amphotericin B (AmB)
      analog with improved solubility and reduced toxicity is immense. Conjugation of
      AmB to arabinogalactan (AG) produced a highly soluble AmB-AG conjugate, with high
      and low molecular weight (H-M(w) and L-M(w)) fractions. Its similar antifungal
      activity to AmB poses the question whether AmB-AG is a prodrug of AmB or a novel
      pharmaceutical entity. We compared the PK of AmB-AG and AmB in rats. Upon AmB-AG
      administration, no free AmB was released. The half-lives and the volumes of
      distribution of AmB, H-M(w) and L-M(w) were 10.9, 8.8, and 1.5 h and 1630, 217,
      and 133 mL/kg, respectively. We conclude that PK of small molecules conjugated to
      polysaccharides is mainly dictated by the macromolecular moiety and shows
      molecular weight dependency. Our findings define AmB-AG as a novel pharmaceutical
      entity with high clinical potential.

PMID- 20690710
TI  - Eosinophil cationic protein aggregation: identification of an N-terminus amyloid
      prone region.
AB  - Eosinophil cationic protein (ECP) is an antimicrobial protein belonging to the
      superfamily of RNase A. ECP exhibits a broad spectrum of action against bacteria
      and, at higher concentrations, displays cytotoxic activity to eukaryotic cells.
      Recently, a powerful aggregation activity for lipid vesicles and for the gram
      negative E. coli specie has also been related to the protein toxicity. Here we
      present the amyloid-like aggregation capacity of ECP. This is the first report of
      amyloid aggregation in a native nonengineered ribonuclease. The ECP aggregates
      are able to bind the amyloid-diagnostic dyes Thioflavin T and Congo Red and
      display a protofibril morphology when observed under electronic microscopy. We
      have also identified an N-terminus hydrophobic patch (residues 8-16) that is
      required for the amyloid aggregation process. A single substitution, I13A, breaks
      the aggregation prone sequence and abolishes the amyloid aggregation ability.
      Moreover, the corresponding R1N19 peptide is able to reproduce the protein
      amyloid-like aggregation behavior. The results may provide new clues on the
      protein antimicrobial mechanism and its toxicity to the host tissues in
      inflammation processes.

PMID- 20690711
TI  - Direct synthesis of quaternized polymer brushes and their application for guiding
      neuronal growth.
AB  - We show that the poly([2-(methacryloyloxy)ethyl]trimethylammonium chloride)
      (PMETA) brush modified surfaces are excellent substrates for the directed growth
      of rat hippocampal neurons, which could prove useful for the coating of neural
      devices. Direct synthesis of quaternized poly(dimethylaminoethyl methacrylate)
      brushes was achieved by surface-initiated atom transfer radical polymerization
      (SI-ATRP) of META in protic media at room temperature. PMETA brushes were
      photolithographically patterned on silicon substrates in combination with
      patterned regions backfilled with short polyethylene glycol (PEG) SAMs. The
      resulting hybrid patterned surfaces consisting of both "cytophilic" and
      "cytophobic" materials were successfully employed to guide a neuronal outgrowth.
      These surfaces should thus provide an excellent platform for studies of neuronal
      function, use in neuronal implants, cell-based biosensors, and other
      applications.

PMID- 20690712
TI  - Effect of environmental factors on hydrolytic degradation of water-soluble
      polyphosphazene polyelectrolyte in aqueous solutions.
AB  - Degradation of a water-soluble polyphosphazene,
      poly[di(carboxylatophenoxy)phosphazene], disodium salt (PCPP) has been studied in
      aqueous solutions at elevated temperature. This synthetic polyelectrolyte is of
      interest as vaccine adjuvant and its degradability constitutes an important
      component of its safety and formulation stability profiles. The degradation
      process is manifested by a gradual reduction in the molecular weight of the
      polymer and cleavage of side groups, which is consistent with previously reported
      data on hydrolytical breakdown of water-soluble polyphosphazenes. The kinetics of
      hydrolytical degradation exhibits distinct pH dependence and the process is
      faster in solutions with lower pH. Remarkably, a number of hydrogen bond forming
      additives, such as polyethylene glycol and Tween displayed a dramatic
      accelerating effect on the degradation of PCPP, whereas inorganic salts, such as
      sodium chloride and potassium chloride, showed a trend for its retardation. The
      results can be potentially explained on the basis of acid promoted hydrolysis
      mechanism and macromolecular interactions in the system.

PMID- 20690713
TI  - Characterization of tunable FGF-2 releasing polyelectrolyte multilayers.
AB  - Fibroblast growth factor 2 (FGF-2) is a potent mediator of stem cell
      differentiation and proliferation. Although FGF-2 has a well-established role in
      promoting bone tissue formation, flaws in its delivery have limited its clinical
      utility. Polyelectrolyte multilayer films represent a novel system for FGF-2
      delivery that has promise for local, precisely controlled, and sustained release
      of FGF-2 from surfaces of interest, including medical implants and tissue
      engineering scaffolds. In this work, the loading and release of FGF-2 from
      synthetic hydrolytically degradable multilayer thin films of various
      architectures is explored; drug loading was tunable using at least three
      parameters (number of nanolayers, counterpolyanion, and type of degradable
      polycation) and yielded values of 7-45 ng/cm(2) of FGF-2. Release time varied
      between 24 h and approximately five days. FGF-2 released from these films
      retained in vitro activity, promoting the proliferation of MC3T3 preosteoblast
      cells. The use of biologically derived counterpolyanions heparin sulfate and
      chondroitin sulfate in the multilayer structures enhanced FGF-2 activity. The
      control over drug loading and release kinetics inform future in vivo bone and
      tissue regeneration models for the exploration of clinical relevance of LbL
      growth factor delivery films.

PMID- 20690714
TI  - Templated mineralization of synthetic hydrogels for bone-like composite
      materials: role of matrix hydrophobicity.
AB  - Bone-mimetic mineral-polymer composite materials have several applications
      ranging from artificial bone grafts to scaffolds for bone tissue engineering;
      templated mineralization is an effective approach to fabricate such composites.
      In this study, we synthesized bone-like composites using synthetic hydrogels
      having pendant side chains terminating with carboxyl groups as a template for
      mineralization. The role of matrix hydrophobicity on mineralization was examined
      using poly(ethylene glycol) hydrogels modified with varying lengths of anionic
      pendant side chains (CH(2) horizontal lineCHCONH(CH(2))(n)COOH, where n = 1, 3,
      5, and 7). The ability of these hydrogels to undergo templated mineralization was
      found to be strongly dependent upon the length of the pendant side chain as is
      evident from the extent of calcification and morphology of the minerals.
      Moreover, mineralized phases formed on the hydrogels were confirmed to resemble
      apatite-like structures. In addition to demonstrating the importance of material
      hydrophobicity as a design parameter for the development of bone-like synthetic
      materials, our study also provides a potential explanation for the in vitro
      differences between the apatite-nucleating capacity of aspartate-rich osteopontin
      and glutamate-rich bone sialoprotein.

PMID- 20690715
TI  - Dendrimers as potential inhibitors of the dimerization of the capsid protein of
      HIV-1.
AB  - Assembly of the mature human immunodeficiency virus type 1 capsid involves the
      oligomerization of the capsid protein, CA. The C-terminal domain of CA, CTD,
      participates both in the formation of CA hexamers and in the joining of hexamers
      through homodimerization. Intact CA and the isolated CTD are able to homodimerize
      in solution with similar affinity (dissociation constant in the order of 10
      microM); CTD homodimerization involves mainly an alpha-helical region. In this
      work, we show that first-generation gallic acid-triethylene glycol (GATG)
      dendrimers bind to CTD. The binding region is mainly formed by residues involved
      in the homodimerization interface of CTD. The dissociation constant of the
      dendrimer-CTD complexes is in the range of micromolar, as shown by ITC. Further,
      the affinity for CTD of some of the dendrimers is similar to that of synthetic
      peptides capable of binding to the dimerization region, and it is also similar to
      the homodimerization affinity of both CTD and CA. Moreover, one of the
      dendrimers, with a relatively large hydrophobic moiety at the dendritic branching
      (a benzoate), was able to hamper the assembly in vitro of the human
      immunodeficiency virus capsid. These results open the possibility of considering
      dendrimers as lead compounds for the development of antihuman immunodeficiency
      virus drugs targeting capsid assembly.

PMID- 20690716
TI  - A temperature-responsive antibody-like nanostructure.
AB  - Antibodies play an essential role in various applications. However, antibodies
      exhibit considerable challenges in applications that require tunable binding
      capabilities and exposure to nonphysiological conditions such as chemical
      conjugation. This study is aimed to develop a novel antibody-like nanostructure
      with special features. The key components of the nanostructure are two DNA
      aptamers and a dendrimer. The aptamers are used to mimic the antigen-binding
      sites of an antibody; the dendrimer is used to provide a defined conjugation site
      for carrying molecules of interest. The results showed that the bivalent
      nanostructure exhibited a high binding affinity and specificity. Moreover, a
      temperature shift from 0 to 37 degrees C would trigger its rapid dissociation
      from the bound target cells, which is not possible in antibody-antigen complexes.
      Thus, an antibody-like nanostructure was successfully developed with novel
      features that natural antibodies do not possess.

PMID- 20690717
TI  - Antioxidant and anti-inflammatory activities of hydroxybenzyl alcohol releasing
      biodegradable polyoxalate nanoparticles.
AB  - p-Hydroxybenzyl alcohol (HBA) is one of phenolic compounds in herbal agents and
      plays a pivotal role in protection against oxidative damage-related diseases due
      to anti-inflammatory effects. We have developed a new biodegradable and anti
      inflammatory peroxalate copolymer in which HBA is chemically incorporated into
      its backbone. The HBA-incorporated copolyoxalate (HPOX) was synthesized from a
      condensation reaction of oxalyl chloride, 1,4-cyclohexamethanol and HBA and was
      capable of releasing pharmaceutically active HBA during hydrolytic degradation.
      HPOX could be dispersed into a single emulsion for the formulation of
      nanoparticles which had a mean size approximately 500 nm in diameter. The
      nanoparticles released HBA which was able to inhibit the production of nitric
      oxide (NO) by suppressing the expression of inducible nitric oxide synthase
      (iNOS) in lipopolysaccharide (LPS)-activated RAW 264.7 macrophage cells. HPOX
      nanoparticles also reduced the production of tumor necrosis factor-alpha (TNF
      alpha). The remarkable features of HPOX are that the polymer degrades completely
      into small molecules and one of degradation products is a pharmaceutically active
      compound. We anticipate that HPOX is highly potent and versatile for the
      treatment of inflammatory diseases.

PMID- 20690718
TI  - Composition and conformation of Cryptosporidium parvum oocyst wall surface
      macromolecules and their effect on adhesion kinetics of oocysts on quartz
      surface.
AB  - We characterized the composition and conformation of Cryptosporidium parvum ( C.
      parvum ) oocyst wall surface macromolecules and studied their effect on
      interactions between C. parvum oocyst and quartz surface. Proteinase K and mixed
      glycosidases were used to modify C. parvum oocyst surface macromolecules. The
      peptides released by proteinase K and carbohydrates hydrolyzed by mixed
      glycosidases were respectively analyzed with liquid
      chromatography/nanoelectrospray ionization tandem mass spectrometry (LC-MS/MS)
      and phenol-sulfuric acid assay to determine the composition of C. parvum oocyst
      wall surface macromolecules. Surface potential and polarity of the untreated and
      proteinase treated C. parvum oocysts revealed information about the conformation
      of oocyst wall surface macromolecules. The results illustrated that C. parvum
      oocyst wall is covered by a fluffy layer of glycoproteins. Adhesion kinetics of
      untreated and proteinase K treated C. parvum oocysts on quartz surface were
      studied in a radial stagnation point flow cell over a wide range of ionic
      strength to investigate the effect of C. parvum oocyst wall surface
      macromolecules on oocysts-quartz interactions. The adhesion rate coefficient of
      proteinase K treated C. parvum oocysts significantly decreased compared to that
      of untreated oocysts. This observation indicated that the fluffy layer on C.
      parvum oocysts wall leads to weaker van der Waals interaction and stronger steric
      repulsion.

PMID- 20690719
TI  - Mechanical properties of ultrahigh molecular weight PHEMA hydrogels synthesized
      using initiated chemical vapor deposition.
AB  - In this work, poly(2-hydroxyethyl methacrylate) (PHEMA), a widely used hydrogel,
      is synthesized using initiated chemical vapor deposition (iCVD), a one-step
      surface polymerization that does not use any solvents. iCVD synthesis is capable
      of producing linear stoichiometric polymers that are free from entrained
      unreacted monomer or solvent and, thus, do not require additional purification
      steps. The resulting films, therefore, are found to be noncytotoxic and also have
      low nonspecific protein adsorption. The kinetics of iCVD polymerization are tuned
      so as to achieve rapid deposition rates ( approximately 1.5 microm/min), which in
      turn yield ultrahigh molecular weight polymer films that are mechanically robust
      with good water transport and swellability. The films have an extremely high
      degree of physical chain entanglement giving rise to high tensile modulus and
      storage modulus without the need for chemical cross-linking that compromises
      hydrophilicity.

PMID- 20690720
TI  - Smart PEGylation of trypsin.
AB  - Thermoresponsive oligo(ethylene glycol)-based copolymers were investigated for
      trypsin conjugation. These copolymers have been synthesized by atom transfer
      radical polymerization of 2-(2-methoxyethoxy)ethyl methacrylate (MEO(2)MA) with
      oligo(ethylene glycol) methyl ether methacrylate (OEGMA(475), M(n) = 475 g.mol(
      1)) at 60 degrees C in the presence of copper(I) chloride and 2,2'-bipyridyl. Two
      different ATRP initiators, containing succinimidyl ester moieties, were tested,
      namely, N-succinimidyl-2-bromopropionate and N-succinimidyl-2-bromoisobutyrate.
      In both cases, ATRP afforded well-defined polymers with a narrow molecular weight
      distribution and controlled chain-ends. However, the efficiency of initiation of
      the two initiators was lower than 1 and therefore the formed polymers exhibited a
      higher than expected mean degree of polymerization. Nevertheless, all types of
      polymers could be conjugated to trypsin. The conjugation reaction was performed
      in borax-HCl buffer. Sodium dodecyl sulfate poly(acrylamide) gel electrophoresis
      (SDS-PAGE) indicated that polymer/enzyme conjugates were obtained in all cases.
      However, (co)polymers initiated by N-succinimidyl-2-bromopropionate led to the
      best conjugation results. The formed P(MEO(2)MA-co-OEGMA(475))-trypsin conjugates
      were found to be thermoresponsive and moreover exhibited a higher enzymatic
      activity than unmodified trypsin.

PMID- 20690721
TI  - Changes in beta-lactoglobulin conformation at the oil/water interface of
      emulsions studied by synchrotron radiation circular dichroism spectroscopy.
AB  - The structure of proteins at interfaces is a key factor determining the stability
      as well as organoleptic properties of food emulsions. While it is widely believed
      that proteins undergo conformational changes at interfaces, the measurement of
      these structural changes remains a significant challenge. In this study, the
      conformational changes of beta-lactoglobulin (beta-Lg) upon adsorption to the
      interface of hexadecane oil-in-water emulsions were investigated using
      synchrotron radiation circular dichroism (SRCD) spectroscopy. Far-UV SRCD spectra
      showed that adsorption of beta-Lg to the O/W interface caused a significant
      increase in non-native alpha-helix structure, accompanied by a concomitant loss
      of beta-sheet structure. Near-UV SRCD spectra revealed that a considerable
      disruption of beta-Lg tertiary structure occurred upon adsorption. Moreover, heat
      induced changes to the non-native beta-Lg conformation at the oil/water interface
      were very small compared to the dramatic loss of beta-Lg secondary structure that
      occurred during heating in solution, suggesting that the interface has a
      stabilizing effect on the structure of non-native beta-Lg. Overall, our findings
      provide insight into the conformational behavior of proteins at oil/water
      interfaces and demonstrate the applicability of SRCD spectroscopy for measuring
      the conformation of adsorbed proteins in optically turbid emulsions.

PMID- 20690722
TI  - Protease-catalyzed oligomerization of hydrophobic amino acid ethyl esters in
      homogeneous reaction media using l-phenylalanine as a model system.
AB  - Enzymatic synthesis of oligopeptides from l-phenylalanine ethyl ester
      hydrochloride (l-Phe-Et.HCl) and other l-form hydrophobic amino acid ester
      hydrochlorides in water miscible organic cosolvents was studied. Different
      proteases, water miscible cosolvents, and effect of different ratios of water
      miscible cosolvents for protease-catalyzed oligo-phenylalanine [oligo(l-Phe)]
      were compared. The importance of the use of water miscible cosolvents in
      transforming reactions from heterogeneous to homogeneous conditions as a potent
      medium engineering tool for protease-catalyzed oligopeptide synthesis is
      highlighted. For example, at 0.125 M l-Phe-Et.HCl, 20% (v/v) methanol, 18.6 mg/mL
      bromelain, in phosphate buffer (0.25M, pH 8), 40 degrees C, for 3 h, oligo(l-Phe)
      precipitated from the solution to yield 45 +/- 5%, in contrast, in the absence of
      cosolvent oligo(l-Phe) yield of 29 +/- 5% was obtained. The following reaction
      conditions were optimized for bromelain catalyzed oligo(l-Phe) synthesis: pH,
      temperature, substrate, enzyme, and cosolvent concentrations. DP(avg) and chain
      length distribution in the product peptides were investigated by (1)H NMR and
      MALDI-TOF.

PMID- 20690723
TI  - Biodegradability and biocompatibility of thermoreversible hydrogels formed from
      mixing a sol and a precipitate of block copolymers in water.
AB  - This study examines in vitro and in vivo biodegradation and biocompatibility of a
      thermogelling polymeric material, which we call a mixture hydrogel. The mixture
      contains two ABA-type triblock copolymers poly(d,l-lactic acid-co-glycolic acid)
      b-poly(ethylene glycol)-b-poly(d,l-lactic acid-co-glycolic acid) (PLGA-PEG-PLGA)
      with different block ratios, and one polymer is soluble in water, but the other
      is not. The aqueous solutions of some mixtures with appropriate mix ratios form
      hydrogels at the body temperature. The degradation of mixture hydrogels proceeded
      by hydrolysis of ester bonds followed by the erosion of gel in phosphate saline
      buffer solution at 37 degrees C for nearly one month. The mass loss and reduction
      of molecular weight were detected. The mix ratio was found to significantly
      influence the degradation profiles. The rapid in vivo gel formation was confirmed
      after subcutaneous injection of the thermogelling copolymer mixtures into Sprague
      Dawley rats. The in vivo degradation was a bit accelerated than in vitro
      hydrolysis, and the persistence time of injected hydrogels in vivo was found to
      be tuned by mix ratio. MTT assay and histological observations were used to
      examine the copolymer mixtures. Both in vitro and in vivo results illustrate
      acceptable biocompatibility of our materials. As such, the thermosensitive
      hydrogel of copolymer mixture is confirmed to be a promising candidate of an
      injectable biomaterial for drug delivery and tissue engineering.

PMID- 20690724
TI  - Hematin is an alternative catalyst to horseradish peroxidase for in situ
      hydrogelation of polymers with phenolic hydroxyl groups in vivo.
AB  - Hematin, an iron-containing porphyrin used in the management of porphyria
      attacks, was evaluated as an alternative catalyst to horseradish peroxidase (HRP)
      for in situ gelation of polymers with phenolic hydroxyl (Ph) moieties in vivo. An
      aqueous solution of gelatin derivative with Ph moieties was gellable in the
      presence of both hematin and H2O2. A total of 98.6% adhesion of L929 fibroblast
      cells 4 h after seeding and their similar morphology to those on substrate coated
      with unmodified gelatin indicated no obvious substrate cytotoxicity. High
      cytocompatibility of the gelation process under conditions inducing gelation
      within 20 s was demonstrated by 95.0% viability of enclosed cells in vitro.
      Furthermore, no adverse effects of hematin were found compared with HRP by
      histological observation of cutaneous tissue surrounding in situ formed gels. The
      versatility of hematin for gelation of a variety of polymers possessing Ph groups
      was demonstrated by the gelation of a carboxymethyl cellulose derivative.

PMID- 20690725
TI  - Control of the electromechanical properties of alginate hydrogels via ionic and
      covalent cross-linking and microparticle doping.

PMID- 20690726
TI  - Carrier system of chemical drugs and isotope from gelatin electrospun nanofibrous
      membranes.

PMID- 20690727
TI  - Controllable synthesis of CuO nanowires and Cu2O crystals with shape evolution
      via gamma-irradiation.
AB  - Copper oxide nanowires and cuprous oxide crystals had been synthesized through
      gamma-irradiating aqueous CuCl(2)-NaOH-sodium dodecyl sulfate (SDS)-isopropyl
      alcohol solutions under ambient conditions. The product composition could be
      changed by modulating the amount of base, NaOH. The morphology of the products
      could be accurately controlled by altering the amounts of SDS and isopropyl
      alcohol. A possible formation mechanism was also proposed.

PMID- 20690728
TI  - A zinc(II)-included hemicryptophane: facile synthesis, characterization, and
      catalytic activity.
AB  - A zinc(II)-included hemicryptophane, which has a zinc(II) center embedded in the
      cavity, was synthesized and characterized. The catalytic activity of the
      hemicryptophane was tested in the hydrolysis of methyl para-nitrophenyl carbonate
      (MPC). A direct comparison between the hemicryptophane and the model complex,
      which lacks a cavity, demonstrated that the cage structure enhanced the catalytic
      activity.

PMID- 20690729
TI  - Anion recognition and sensing by a new macrocyclic dinuclear copper(II) complex:
      a selective receptor for iodide.
AB  - A macrocyclic dinuclear copper complex, [Cu(2)(II)(1)Br(3)(H(2)O)]Br, has been
      synthesized and characterized by X-ray crystallography, in which the macrocycle
      is folded to form a bowl-shaped cavity. The sensing ability of the receptor has
      been studied for halides by UV-vis spectroscopy in water-acetonitrile (1:3, v/v)
      and water. The results indicate that the new receptor exhibits a strong affinity
      and selectivity for iodide.

PMID- 20690730
TI  - A modular approach to redox-active multimetallic hydrophobes of discoid topology.
AB  - A new modular [Fe(II)(Fe(III)L(2))(3)](PF(6))(2) species with discoid (disk-like)
      topology exhibits redox and surfactant properties and points to a new approach
      for multimetallic Langmuir film precursors.

PMID- 20690731
TI  - Conformationally constrained (coumarin-triazolyl-bipyridyl) click fluoroionophore
      as a selective Al3+ sensor.
AB  - A conformationally constrained (coumarin-pyrrolidinyl-triazolyl-bipyridyl)
      fluoroionophore conjugate was synthesized through click chemistry. The
      fluoroionophore serves as a selective chemosensor for Al(3+) based on internal
      charge transfer. The coumarin-bipyridyl chemosensor exhibited a high association
      constant with submicromolar detection for the aluminum ion.

PMID- 20690732
TI  - Self-assembly and chiral recognition of a two-dimensional coordination polymer
      from a chiral nickel(II) macrocyclic complex and trimesic acid.
AB  - A two-dimensional chiral open framework,
      [Ni(L(R,R))](3)[C(6)H(3)(COO)(3)](2).12H(2)O.CH(3)CN (3), is prepared from a
      nickel(II) macrocyclic complex with chiral pendants and benzenetricarboxylate in
      MeCN/H(2)O and characterized [L(R,R) = 1,8-bis[(R)-alpha-methylbenzyl]
      1,3,6,8,10,13-hexaazacyclotetradecane]. The open framework shows selective chiral
      recognition by interactions between the solid 3 and rac-1,1'-bi-2-naphthol.

PMID- 20690733
TI  - Oxidative cyclization of a phenolic Schiff base and synthesis of a cyclometalated
      ruthenium nitrosyl complex: photoinduced NO release by visible light.
AB  - The reactivity of sigma-arylruthenium cyclometallate [Ru(L(SB1))(PPh(3))(2)Cl]
      [1; L(SB1)H(2) = 4-methyl-2-(4-nitrobenzylideneamino)phenol] with nitric oxide
      (NO) gave rise to nitrosylation at the metal center, ring nitration, and
      oxidative cyclization, affording benzoxazole derivative formation. The molecular
      structure of the resultant nitrosyl complex,
      [Ru(L(PB1))(PPh(3))(2)(NO)Cl](ClO(4)) [2; L(PB1)H = 5-methyl-7-nitro-2-(4
      nitrophenyl)benzoxazole] was determined, and a different sigma-arylruthenium
      cyclometallate was characterized in which the benzoxazole derivative was found to
      be coordinated to the metal center. The crystal structure and IR and NMR spectral
      data confirmed the formation of a diamagnetic {RuNO}(6) species with a S = 0
      ground state and a {Ru(II)NO(+)}(6) description of the {RuNO}(6) moiety.
      Coordinated NO in the resultant complex 2 was photolabile under visible light and
      was transferred to reduced myoglobin.

PMID- 20690734
TI  - Reversible hydrogen activation by the Pt complex Pt(Sn(t)Bu3)2(CNtBu)2.
AB  - The new platinum complex Pt(Sn(t)Bu(3))(2)(CN(t)Bu)(2)(H)(2), 1, was obtained in
      32% yield from the reaction of Pt(COD)(2) with (t)Bu(3)SnH and CN(t)Bu at room
      temperature. Compound 1 is a mononuclear 18 electron platinum complex in an
      octahedral geometry which contains two Sn(t)Bu(3)'s, two CN(t)Bu's, and two
      hydride ligands. The two hydride ligands in 1 can be eliminated, both in solution
      and in the solid state, to yield the 16 electron complex
      Pt(Sn(t)Bu(3))(2)(CN(t)Bu)(2), 2. Compound 2 reacts with hydrogen at room
      temperature in solution and in the solid state to regenerate 1.

PMID- 20690735
TI  - Construction of a novel Zn-Ni trinuclear Schiff base and a Ni2+ chemosensor.
AB  - A novel Zn-Ni heterotrinuclear Schiff base compound bearing acacen(2-) moieties
      was constructed through the selective assembly of a chemosensor Schiff base zinc
      compound with a Ni(2+) ion. Its crystal structure not only clearly explains the
      binding mode between the chemosensor molecule and the detected metal ion but also
      represents the first trinuclear complex based on a symmetric acacen(2-) base
      Schiff base.

PMID- 20690736
TI  - Polymorphic crystal approach to changing the emission of [AuCl(PPh3)2], analyzed
      by direct observation of the photoexcited structures by X-ray
      photocrystallography.
AB  - The photoexcited charge-transferred state of [AuCl(PPh(3))(2)] in a novel
      polymorphic crystal form was directly observed by X-ray photocrystallographic
      analysis. Its photoexcited state was completely different from the one generated
      in the known crystal of [AuCl(PPh(3))(2)]; the photoexcited bond-shrunk state was
      generated in the known crystal. This difference in the generated photoexcited
      state was clearly reflected by the difference in emission color. While the known
      crystal form showed green phosphorescence, the novel form showed blue
      phosphorescence under UV irradiation. The difference in the generated
      photoexcited state was due to the differences in steric hindrance in the crystal;
      bond shortening by photoexcitation was sterically allowed in the known form,
      while on the other hand, it was restricted in the novel form. Therefore, instead
      of the bond-shrunk state, the charge-transferred excited state became the lowest
      triplet state, and the emission color changed from green to blue (i.e., a blue
      shift of the emission wavelength was observed). These results mean that the
      photoexcited structure and the emission color of [AuCl(PPh(3))(2)] can be
      controlled by designing the molecular environment in the crystal.

PMID- 20690737
TI  - Sugars to control ligand shape in metal complexes: conformationally constrained
      glycoligands with a predetermination of stereochemistry and a structural control.
AB  - In coordination chemistry, ligand shape can be used to tune properties, such as
      metal selectivity, coordination number, electronic structure, redox potential,
      and metal center stereochemistry including coordination helicates formation, and
      also to generate cavities for encapsulation. The results presented in this
      article indicate that two epimeric glycoligands (3 and 4) based on the
      conformationally restrained xylo- and ribo-1,2-O-isopropylidenefurano scaffolds
      are preorganized in water through pi-pi stacking due to hydrophobic interactions,
      as evidenced from excimer observation. The structure obtained in the solid state
      for one of the Cu(II) complexes (5) is chiral, with an original helical chirality
      arising from the coiling of the two ligands around the Cu-Cu axis. It shows an
      unusual double-deck type structure, with pi-pi interaction between two triazoyl
      pyridyl rings and with a small cavity between the two Cu(II) ions able to host a
      bridging water molecule, as suggested by electron paramagnetic resonance. The
      Cu(II) complex from the epimeric ligand (6) shows similar properties with a
      mirror-image CD spectrum in the d-d region of the Cu(II). There is a
      predetermination of chirality at the metal center by the glycoligand induced by
      the C3 configuration, 6 and 5 being pseudoenantiomers. Interestingly, the
      stereochemistry at the metal center is here controlled by the combination of pi
      stacking and chiral backbone.

PMID- 20690738
TI  - Trimethylsilylchalcogenolates of Co(II) and Mn(II): from mononuclear coordination
      complexes to clusters containing -ESiMe3 moieties (E = S, Se).
AB  - The Co(II) and Mn(II) complexes (tmeda)Co(ESiMe(3))(2) (E = S, 1a; E = Se, 1b),
      (3,5-Me(2)C(5)H(3)N)(2)Co(ESiMe(3))(2) (E = S, 2a; E = Se, 2b),
      [Li(tmeda)](2)[(tmeda)Mn(5)(mu-ESiMe(3))(2)(ESiMe(3))(4)(mu(4)-E)(mu(3)-E)(2)] (E
      = S, 3a; E = Se, 3b), [Li(tmeda)](2)[Mn(SSiMe(3))(4)] (4),
      [Li(tmeda)]4[Mn(4)(SeSiMe(3))(4)(mu(3)-Se)(4)] (5), and
      [Li(tmeda)](4)[Mn(Se(4))(3)] (6) (tmeda = N,N,N',N'-tetramethylethylenediamine)
      have been isolated from reactions of Li[ESiMe(3)] and the chloride salts of these
      metals. The treatment of (tmeda)CoCl(2) with two equivalents of Li[ESiMe(3)] (E =
      S, Se) yields 1a and 1b, respectively, whereas similar reactions with MnCl(2)
      yield the polynuclear complexes 3a (E = S) and 3b (E = Se). The selective
      preparation of the mononuclear complex 4 is achieved by increasing the reaction
      ratios of Li[SSiMe(3)] to MnCl(2) to 4:1. Single crystal X-ray analysis of
      complexes 1-5, confirms the presence of the trimethylsilylchalcogenolate moieties
      and distorted tetrahedral geometry around the metal centers in each of these
      complexes. The structure of the tris(tetraselenide) complex
      [Li(tmeda)](4)[Mn(Se(4))(3)] (6), isolated in small quantities from the
      preparation of 5, is also described.

PMID- 20690739
TI  - Photophysical characterization of the interactions among tris(2,2'
      bipyridyl)ruthenium(II) complexes ion-exchanged within zirconium phosphate.
AB  - We studied the structures, luminescence, and self-quenching properties of
      tris(2,2'-bipyridyl)ruthenium(II) (Ru(bpy)(3)(2+)) two-dimensional arrangements
      within the layers of zirconium phosphate (ZrP). The intercalation of
      Ru(bpy)(3)(2+) was accomplished using a hydrated form of zirconium phosphate ZrP.
      Varying the Ru(bpy)(3)(2+)/ZrP intercalation ratio, different Ru(bpy)(3)(2+)
      exchanged ZrP loading levels were achieved. The ion exchange of Ru(bpy)(3)(2+)
      within ZrP produces a red shift in the metal-to-ligand charge-transfer (MLCT)
      absorption band of the complex from 452 nm in aqueous solution to 460 nm in ZrP.
      Steady state luminescence spectra of the Ru(bpy)(3)(2+)-exchanged ZrP materials
      show an increase in the luminescence intensity with an increase in the
      Ru(bpy)(3)(2+) loading level until about 0.77 M, where subsequent increases in
      the loading level produce a decrease in the luminescence (self-quenching region).
      Time-resolved luminescence measurements are consistent with the steady state
      luminescence measurements. Analysis of the time domain luminescence measurements
      in loadings higher than 0.77 M leads to the determination of a collisional
      quenching rate constant of (1.67 +/- 0.05) x 10(6) M(-1) s(-1). Stern-Volmer
      analysis of the luminescence quantum yield of Ru(bpy)(3)(2+)-exchanged ZrP
      materials indicates that static quenching is also involved in the Ru(bpy)(3)(2+)
      self-quenching mechanism. The quantum yield data behavior might be explained by a
      model that takes into account collisional quenching and the quasi-static Perrin
      mechanism. The calculation yields a quenching sphere of action of 14.8 A, which
      is slightly larger than the collisional radii of two Ru(bpy)(3)(2+) ions (12.2
      A), as predicted by the model.

PMID- 20690740
TI  - Zinc, cadmium, and mercury complexes with fluorinated selenolate ligands.
AB  - Reductive cleavage of C(6)F(5)SeSeC(6)F(5) with elemental M (M = Zn, Cd, and Hg)
      in pyridine results in the formation of (py)(2)Zn(SeC(6)F(5))(2),
      (py)(2)Cd(SeC(6)F(5))(2), and Hg(SeC(6)F(5))(2). Structural characterization of
      the Zn and Cd compounds reveals tetrahedral coordination environments, while the
      Hg compound shows a complicated series of linear structures with two short,
      nearly linear Hg-Se bonds, up to two longer and perpendicular Hg...Se
      interactions, and no coordinated pyridine ligands. All three compounds exhibit
      well-defined intermolecular pi-pi-stacking interactions in the solid state. They
      are volatile and decompose at elevated temperatures to give MSe and either
      (SeC(6)F(5))(2) or Se(C(6)F(5))(2).

PMID- 20690741
TI  - CO releasing properties and cytoprotective effect of cis-trans
      [Re(II)(CO)2Br2L2]n complexes.
AB  - The carbon monoxide (CO) releasing properties of a series of rhenium(II)-based
      complexes of general formula cis-trans-[Re(II)(CO)(2)Br(2)L(2)](n) and cis-trans
      [Re(II)(CO)(2)Br(2)N[intersection]N] (where L = monodentate and N[intersection]N
      = bidentate ligand) are reported. Complexes evaluated in this study were obtained
      from direct ligand substitution reactions of the cis-[Re(II)(CO)(2)Br(4)](2-)
      synthon (2) recently described. (1) All molecules have been fully characterized.
      The solid-state structures of the cis-trans-[Re(II)(CO)(2)Br(2)L(2)] (with L = N
      methylimidazole (3), benzimidazole (4) and 4-picoline (5)) and the cis-trans
      [Re(II)(CO)(2)Br(2)N[intersection]N] (with N[intersection]N = 4,4'-dimethyl-2,2'
      bipyridine (8) and 2,2'-dipyridylamine (11)) adducts are presented. The release
      of CO from the cis-trans-[Re(II)(CO)(2)Br(2)L(2)](n) complexes was assessed
      spectrophotometrically by measuring the conversion of deoxymyoglobin (Mb) to
      carbonmonoxy myoglobin (MbCO). Only compounds bearing monodentate ligands were
      found to liberate CO. The rate of CO release was found to be pH dependent with
      half-lives (t(1/2)) under physiological conditions (25 degrees C, 0.1 M phosphate
      buffer, and pH 7.4) varying from ca. 6-43 min. At lower pH values, the time
      required to fully saturate Mb with CO liberated from the metal complexes
      gradually decreased. Complex 2 and the cis-trans-[Re(II)(CO)(2)Br(2)(Im)(2)]
      adduct (with Im = imidazole (6)) show a protective action against "ischemia
      reperfusion" stress of neonatal rat ventricular cardiomyocytes in culture.

PMID- 20690742
TI  - Synthesis, crystal structure, and characterization of a heterometallic one
      dimensional complex with metal-metal bonds.
AB  - The quasi-one-dimensional chain
      [{PtRh(TCM)(2)(NH(3))(2)Cl(2.5)}(2){Pt(2)(PVM)(2)(NH(3))(4)}(2)](n)(PF(6))(6n).2n
      (2)O (Chain-2; TCM = Cl(3)CCONH(-), PVM = (t)BuCONH(-)), which consists of Pt and
      Rh atoms, has been obtained from two dinuclear compounds,
      [Pt(2)(PVM)(2)(NH(3))(4)](PF(6))(2).H(2)O (1) and [PtRh(TCM)(2)(NH(3))(2)Cl(3)]
      (2). Single-crystal X-ray analysis showed that the dinuclear compounds stack with
      metal-metal bonds to form octameric units, Pt-Rh-Pt-Pt-Pt-Pt-Rh-Pt (Pt(6)Rh(2)),
      that are bridged by the Cl(-) ion to be a quasi-one-dimensional chain. Elemental
      analysis, X-ray photoelectron spectroscopy, electron paramagnetic resonance
      (EPR), and magnetic susceptibility measurements showed that Chain-2 has a mixed
      valency and one unpaired electron per octameric Pt(6)Rh(2) unit. Taking into
      account the small observed g(av) value (g(av) = 2.01 at room temperature)
      obtained by EPR measurement and B3LYP density functional theory calculations of
      the model complex, oxidation states of the octameric unit are postulated to be
      Pt(3+)-Rh(2.5+)-Pt(2+)-Pt(2+)-Pt(2+)-Pt(2+)-Rh(2.5+)-Pt(3+), where the EPR
      isotropic signal showed that the unpaired electron resides in the Rh d(xy)
      orbitals (delta* orbitals in Pt-Rh dinuclear parts) and hops from one Rh atom to
      another.

PMID- 20690743
TI  - Bistrimethylsilylamide transition-metal complexes as starting reagents in the
      synthesis of ternary Cd-Mn-Se cluster complexes.
AB  - The use of bis-trimethylsilylamide transition-metal complexes soluble in organic
      solvents offers new perspectives for the synthesis of metal chalcogenide cluster
      molecules, especially for multicomponent clusters. This is illustrated by the
      synthesis of the mixed cadmium-manganese chalcogenide clusters
      [Cd(4)Mn(6)Se(4)(SePh)(12)(P(n)Pr(3))(4)] and
      [Cd(4)Mn(4)S(SePh)(14)(P(n)Pr(3))(2)] as reported here. These cluster molecules
      display interesting properties, such as a photoluminescence in the red to near
      infrared spectral region, which is particularly bright at temperatures below
      approximately 100 K, and an antiferromagnetic coupling between the manganese(II)
      ions. Electrospray Fourier transform ion cyclotron resonance mass spectra from
      the chemically charged clusters in solution show several ionic cluster species
      which indicate a fast Cd/Mn exchange in solution. Furthermore, single crystal X
      ray analysis and magnetic measurements supported by density functional theory
      calculations suggest a cocrystallization of structural isomers of the ideal
      cluster composition [Cd(4)Mn(4)S(SePh)(14)(P(n)Pr(3))(2)] as well as of species
      with the general formula [Cd(4+x)Mn(4-x)S(SePh)(14)(P(n)Pr(3))(2)] (x < 0 Mn
      enrichment; x > 0 Cd enrichment) without a significant decrease in the stability.
      Thermal cleavage of [Cd(4)Mn(6)Se(4)(SePh)(12)(P(n)Pr(3))(4)] results, in
      agreement with the CdSe/MnSe phase diagram, in the formation of a mixture of a
      hexagonal phase Cd(1-x)Mn(x)Se (x approximately 0.5) and a cubic phase Mn(1
      x)Cd(x)Se (x < 0.05).

PMID- 20690744
TI  - Unsymmetric Ru(II) complexes with N-heterocyclic carbene and/or terpyridine
      ligands: synthesis, characterization, ground- and excited-state electronic
      structures and their application for DSSC sensitizers.
AB  - Three ruthenium(II) complexes with N-heterocyclic carbene (NHC) or
      NHC/2,2':6',2''-terpyridine (tpy) hybrid ligands, bis[2,6-bis(3-methylimidazol-3
      ium-1-yl)pyridine-4-carboxylic acid]ruthenium(II) (BCN), [2,6-bis(3
      methylimidazolium-1-yl)pyridine-4-carboxylic acid](2,2';6'2''
      terpyridine)ruthenium(II) (TCN), and [2,6-bis(3-methylimidazol-3-ium-1
      yl)pyridine](2,2';6'2''-terpyridine-4'-carboxylic acid)ruthenium(II) (CTN), have
      been synthesized and characterized by (1)H and (13)C NMR, high-resolution mass
      spectrometry, and elemental analysis. The molecular geometry of the TCN complex
      was determined by X-ray crystallography. Electronic absorption spectra of these
      complexes exhibit typical pi-pi* and metal-to-ligand charge transfer bands in the
      UV and visible regions, respectively. The lowest energy absorption maxima were
      430, 448, and 463 nm with molar extinction coefficients of 28,100, 15,400, and
      7400 M(-1)cm(-1) for BCN, TCN, and CTN, respectively. Voltammetric data suggest
      that energy levels of the highest occupied molecular orbitals (HOMOs) of the
      three complexes reside within a 10 meV window despite the varying degrees of
      electronic effect of the constituent ligands. The electronic structures of these
      complexes calculated via density functional theory (DFT) indicate that the three
      HOMOs and the three lowest unoccupied MOs (LUMOs) are metal and ligand centered
      in character, for the former and the latter, respectively. Time-dependent DFT (TD
      DFT) calculation predicts that the lowest energy absorption bands of each complex
      are comprised of multiple one-electron excitations. TD-DFT calculation also
      suggests that the background of spectral red shift stems most likely from the
      stabilization of unoccupied MOs rather than the destabilization of occupied MOs.
      The overall efficiencies of the dye-sensitized solar cell systems of these
      complexes were found to be 0.48, 0.14, and 0.10% for BCN, TCN, and CTN,
      respectively, while that of a commercial bis(4,4'-dicarboxylato-2,2'-bipyridine)
      bis(isothiocyanoto)ruthenium(II) (N719) system was 6.34%.

PMID- 20690745
TI  - New iridathiaboranes with reversible isonido <--> nido cluster flexibility.
AB  - The reaction between [IrCl(CO)(PMe(3))(2)] and the Cs[arachno-6-SB(9)H(12)] salt
      in CH(2)Cl(2) yields pale-yellow 11-vertex [8,8,8-(CO)(PMe(3))(2)-nido-8,7
      IrSB(9)H(10)] (4). Reaction of this CO-ligated iridathiaborane with Me(3)N=O
      affords pale-yellow 11-vertex [1,1,1-(H)(PMe(3))(2)-isonido-1,2-IrSB(9)H(9)] (6),
      which is also formed from the thermal decarbonylation of 4. Compound 4 has a
      conventional cluster structure based on classical 11-vertex nido geometry, with
      the iridium center and the sulfur atom in the adjacent 8- and 7-positions on the
      pentagonal open face. Compound 6 exhibits an 11-vertex isonido structure based on
      an octadodecahedron with the {Ir(H)(PMe(3))(2)} occupying the apical position of
      connectivity six, but with one long non-bonding Ir-B distance generating the
      quadrilateral isonido open-face. Compound 6 reverts to 4 upon reaction with CO,
      and the Lewis acid character of 6 is further demonstrated in the reaction with
      EtNC to give [8,8,8-(EtNC)(PMe(3))(2)-nido-8,7-IrSB(9)H(10)] (7). The three new
      compounds 4, 6, and 7 have been characterized by single-crystal X-ray diffraction
      analyses and by NMR spectroscopy. Each of the nido iridathiaboranes 4 and 7
      exhibits two different {Ir(L)(PMe(3))(2)}-to-{SB(9)H(10)} conformers in solution
      and in the solid state. Density functional theory (DFT) calculations reveal that
      the iridium atom inverts the nido-isonido-closo energy profile previously found
      for the rhodathiaborane congener [8,8-(PPh(3))(2)-nido-8,7-RhSB(9)H(10)] (3),
      demonstrating how the structure of these 11-vertex clusters can be controlled and
      fine-tuned by the tailoring of the metal center.

PMID- 20690746
TI  - Structural and electronic effects in the metalation of porphyrinoids. Theory and
      experiment.
AB  - The structure-reactivity relationships in metalation reactions of porphyrinoids
      have been studied using experimental and theoretical methods. A series of eight
      porphyrinoic ligands, derivatives of chlorophylls, was prepared in which both the
      peripheral groups and the degrees of saturation of the macrocycle were
      systematically varied. To reveal the solvent and structural factors which control
      the interactions of these macroligands with metal centers, their interactions
      with reactive Zn(2+) and inert Pt(2+) ions were investigated using absorption
      spectroscopy. In parallel, quantum chemical calculations (density functional
      theory, DFT) were performed for the same set of molecules to examine the
      influence of structural and electronic factors on the energy of the frontier
      orbitals, the nucleophilicity/electronegativity of the macrocycle, its hardness,
      and conformation. These static descriptors of chemical reactivity, relevant to
      metalation reactions, were verified against the results obtained in the
      experimental model. The experimentally obtained kinetic data clearly show that
      the solvent has a crucial role in the activation of the incoming metal center. In
      terms of chelator structure, the largest effects concern the size of the
      delocalized pi-electron system and the presence of side groups. Both the DFT
      calculations and experimental results show the strong influence of the macrocycle
      rigidity and of the peripheral groups on the chelating ability of porphyrinoids.
      In particular, the peripheral functionalization of the macrocyclic system seems
      to drastically reduce its reactivity toward metal ions. The effect of peripheral
      groups is two-fold: (i) a lower electron density on the core nitrogens, and (ii)
      increased rigidity of the macrocycle. The outcomes of the theoretical and
      experimental analyses are discussed also in terms of their relevance to the
      mechanism of biological metal insertion in the biosynthesis of heme and
      chlorophyll.

PMID- 20690747
TI  - Tetrathiafulvalene-tetracarboxylate: an intriguing building block with
      versatility in coordination structures and redox properties.
AB  - The synthesis of the transition metal coordination polymers containing a
      tetrathiafulvalene (TTF) moiety substituted with a tetracarboxylate group of the
      formulas [Mn(L)(0.5)(phen)(H(2)O)(2)](n).nH(2)O (1), [Mn(L)(0.5)(bpy)](n).nH(2)O
      (2), [Mn(L)(0.5)(bpy)(CH(3)OH)](n).2nH(2)O (3), and
      [Cu(L)(0.5)(bpy)(DMF)](n).n(DMF) (4) (L(4-) = TTF-tetracarboxylate; phen = 1,10
      phenanthroline; bpy = 2,2'-bipyridine) is reported. Complex 1 is a two
      dimensional (2-D) coordination polymer constructed of infinite carboxylate
      bridged Mn(II) chains and TTF moiety linkages. Complex 2 possesses a 3-D
      polymeric structure formed by infinite -Mn-(O-C-O)(2)-Mn- bridged one-dimensional
      (1-D) chains, which are further coordinated by TTF-tetracarboxylate ligands of
      two different orientations. Both complexes 3 and 4 show 1-D extended chain
      structures but are constituted by different dinuclear metal(II) units with a -Mn
      (O-C-O)(2)-Mn- bridge in 3 and a -Cu-(O)(2)-Cu- bridge in 4. Electrochemical
      study of the solid-state compounds attests to the redox activity of the
      coordination system. Magnetic investigations reveal the existence of
      antiferromagnetic interactions between magnetic centers in complexes 3 and 4,
      while in 1, the paramagnetic metallic centers are isolated, in agreement with the
      solid-state structure.

PMID- 20690748
TI  - Structure, stereochemistry, and physico-chemical properties of trinuclear and
      dinuclear metal(II) complexes of a phenol-based tetrapodal Schiff base ligand.
AB  - The tetrapodal ligand 1,1,1,1-tetrakis[(salicylaldimino)methyl]methane (H(4)L)
      has been used to synthesize a number of divalent metal complexes, which include
      (i) the trinuclear compounds [Mg(3)(HL)(2)].nH(2)O (1), [Ni(3)(HL)(2)].2C(7)H(8)
      (3), [Ni(3)L'(2)].0.5C(7)H(8) (4), [Co(3)(HL)(2)] (5), and [Co(3)L'(2)].C(6)H(6)
      (6); (ii) the dinuclear compounds [Ni(2)L] (2), [Cu(2)L].CH(3)CN (8), and
      [Pd(2)L] (9); (iii) an unusual dimeric compound [{Ni(H(2.5)L)}(2)](ClO(4)).2H(2)O
      (7); and (iv) the inclusion compounds [Ni(2)L subset NaClO(4)].CH(3)CN (10) and
      [Cu(2)L subset NaClO(4)] (11). The molecular structures of compounds 1, 3, 4, 6,
      7, and 10 have been determined. In [M(3)(HL)(2)] complexes, one of the
      salicylaldimine chelating units remains uncoordinated, which on being hydrolyzed
      is transformed to the amine-ending complex [M(3)L'(2)]. All of the trinuclear
      complexes have the same core coordination sphere [N(3)M(mu-O(phenolate))(3)M(mu
      O(phenolate))(3)MN(3)] where the terminal metals are connected to the central
      metal via face-shared phenolate oxygens. In the trinuclear compounds, the
      terminal metals are distorted from octahedral to trigonal prismatic to different
      extents in 1 and 6, while in 3 and 4 they are trigonal antiprismatically
      distorted. The stereochemical configurations obtained by the terminal metals in 3
      and 6 are homochiral (Delta...Delta), but heterochiral (Lambda...Delta) in 1 and
      4. In compound 7, the two mononuclear complex units are held together by three
      equivalent O...H...O bridges, indicating 50% deprotonation of all the metal
      coordinated phenols. The temperature-dependent magnetic behavior of 7 has
      indicated the presence of very weak antiferromagnetic exchange coupling (J = -0.2
      cm(-1)) between the two nickel(II) centers. Very similar magnetic behavior
      observed for the trinuclear nickel(II) compounds 3 and 4 is attributed to a
      ferromagnetic exchange interaction between the adjacent metals (J = 7.6 cm(-1)),
      although an interaction between the terminal metals is absent; in contrast, the
      adjacent cobalt(II) centers in 6, however, are involved in an antiferromagnetic
      exchange interaction (J = -5.7 cm(-1)). The dinuclear complexes [M(2)L], in which
      each of the metal centers are chelated with a pair of salicylaldimines, act as
      hosts (when M = Ni and Cu) for alkali metals (Li(+), Na(+), and K(+)). The host
      guest binding constants (K) have been determined in (CH(3))(2)SO solution, and
      the results show that [Ni(2)L] is a better host compared to [Cu(2)L]. The
      decreasing order of K values for both hosts is Na(+) > Li(+) > K(+). [Ni(2)L
      subsetNaClO(4)].CH(3)CN (10) has been shown to have a polymeric structure in
      which sodium is octahedrally surrounded by four nickel-coordinated phenolate and
      two perchlorate oxygens. The magnesium(II) complex 1 exhibits strong fluorescence
      in CH(2)Cl(2) at room temperature with lambda(em) = 425 nm, and the lifetime for
      fluorescent decay is 18.5 ns. The thermal behaviors of 3 and 6 with regard to
      their loss of aromatic solvent molecules have been studied. The evolution of the
      toluene molecules from 3 takes place between 140 degrees and 230 degrees C, while
      the benzene is evolved between 100 degrees and 180 degrees C in 6. The enthalpy
      of desolvation of 3 is 43.4 kJ mol(-1).

PMID- 20690749
TI  - Structural, transport, and electrochemical investigation of novel AMSO4F (A = Na,
      Li; M = Fe, Co, Ni, Mn) metal fluorosulphates prepared using low temperature
      synthesis routes.
AB  - We have recently reported a promising 3.6 V metal fluorosulphate (LiFeSO(4)F)
      electrode, capable of high capacity, rate capability, and cycling stability. In
      the current work, we extend the fluorosulphate chemistry from lithium to sodium
      based systems. In this venture, we have reported the synthesis and crystal
      structure of NaMSO(4)F candidates for the first time. As opposed to the triclinic
      based LiMSO(4)F phases, the NaMSO(4)F phases adopt a monoclinic structure. We
      further report the degree and possibility of forming Na(Fe(1-x)M(x))SO(4)F and
      (Na(1-x)Li(x))MSO(4)F (M = Fe, Co, Ni) solid-solution phases for the first time.
      Relying on the underlying topochemical reaction, we have successfully synthesized
      the NaMSO(4)F, Na(Fe(1-x)M(x))SO(4)F, and (Na(1-x)Li(x))MSO(4)F products at a low
      temperature of 300 degrees C using both ionothermal and solid-state syntheses.
      The crystal structure, thermal stability, ionic conductivity, and reactivity of
      these new phases toward Li and Na have been investigated. Among them, NaFeSO(4)F
      is the only one to present some redox activity (Fe(2+)/Fe(3+)) toward Li at 3.6
      V. Additionally, this phase shows a pressed-pellet ionic conductivity of 10(-7) S
      x cm(-1). These findings further illustrate the richness of the fluorosulphate
      crystal chemistry, which has just been recently unveiled.

PMID- 20690750
TI  - Synthesis, characterization, and quantum-chemical studies of Ni(CN)2MX (M = Rb,
      Cs; X = Cl, Br).
AB  - A new series of coordination-network compounds containing Ni(CN)(2) and MX (M =
      Rb, Cs; X = Cl, Br) quasi two-dimensional sheets has been synthesized and
      structurally characterized. The tetragonal crystal structure (I4/mmm, no. 139)
      can be derived from the distorted perovskite type. Chemically, the Lewis-acidic
      Ni(CN)(2) moieties accept halide ligands, resulting both in slightly elongated
      [Ni(NC)(4)X(2)](4-) octahedra and strongly elongated [Ni(CN)(4)X(2)](4-)
      octahedra that are charge-balanced by M(+) cations. Quantum-chemical calculations
      of the effective Hamiltonian crystal field (EHCF) type indicate the simultaneous
      presence of high- and low-spin Ni(2+) in a 1:1 ratio, in agreement with GGA+U and
      UV studies reported here. Our magnetic susceptibility data also corroborate the
      theoretical findings. An analysis of the magnetic superexchange paths in the new
      series of compounds is performed as well as that of the tentative magnetic state
      of the series.

PMID- 20690751
TI  - Syntheses and magnetostructural investigations on Kuratowski-type homo- and
      heteropentanuclear coordination compounds [MZn4Cl4(L)6] (M(II) = Zn, Fe, Co, Ni,
      or Cu; L = 5,6-dimethyl-1,2,3-benzotriazolate) represented by the nonplanar
      K(3,3) graph.
AB  - Homo- and heteropentanuclear coordination compounds [MZn(4)Cl(4)(L)(6)] (M(II) =
      Zn, Fe, Co, Ni, or Cu; L = 5,6-dimethyl-1,2,3-benzotriazolate) were prepared
      containing mu(3)-bridging N-donor ligands (1,2,3-benzotriazolate), which are
      structurally related to the fundamental secondary building unit of Metal-organic
      Framework Ulm University-4 (MFU-4). The unique topology of these T(d)-symmetrical
      compounds is characterized by the nonplanar K(3,3) graph, introduced into graph
      theory by the mathematician Casimir Kuratowski in 1930. The following "Kuratowski
      type" compounds were investigated by single-crystal X-ray structure analysis:
      [MZn(4)Cl(4)(Me(2)bta)(6)].2DMF (M(II) = Zn, Fe, Co, and Cu; DMF = N,N'
      dimethylformamide) and [MZn(4)Cl(4)(Me(2)bta)(6)].2C(6)H(5)Br (M(II) = Co and Ni;
      C(6)H(5)Br = bromobenzene). The mu(3)-bridging benzotriazolate ligands span the
      edges of an imaginary tetrahedron, in the center of which a redox-active
      octahedrally coordinated M(II) ion is placed. Four Zn(II) ions are located at the
      corners of the coordination units. Each Zn center is bound to a monodentate Cl(-)
      anion and three N-donor atoms stemming from different benzotriazolate ligands.
      The fact that open-shell redox-active M(II) ions can be introduced selectively
      into the central octahedral coordination sites is unambiguously proven by a
      combination of magnetic measurements, UV-vis spectroscopy, and energy-dispersive
      X-ray and inductively coupled plasma atomic emission spectrometry analysis. The
      phase purity of all compounds was checked by powder X-ray diffractometry, IR
      spectroscopy, and elemental analysis. The electronic spectra and magnetic
      properties of the compounds are in complete agreement with their structures
      determined from single-crystal data. Thermogravimetric analysis shows that all
      compounds possess a high thermal stability up to 673 K. The pentanuclear
      compounds retain their structural integrity in solution, as evidenced by time-of
      flight mass spectrometry analysis and comparative solution and solid-state
      diffuse-reflectance spectroscopy. High stability paired with the presence of
      redox-active metal ions and Lewis-acidic Zn centers renders Kuratowski-type
      compounds structural and functional models for future MFU-4-type bi- and
      multifunctional heterogeneous catalysts.

PMID- 20690752
TI  - Para-quinone-containing bis(pyrazol-1-yl)methane ligands: coordination behavior
      toward Co(II) and a C-H activation reaction with Ce(IV).
AB  - Two series of sterically demanding para-dimethoxyphenyl-substituted bis(pyrazol-1
      yl)methane ligands have been synthesized, i.e., L2(R,R') =
      ((MeO)(2)C(6)H(3))C(H)(pz(R,R'))(2) and L3(R,R') =
      ((MeO)(2)C(6)H(3))C(Me)(pz(R,R'))(2) (R,R' = 3-Me,5-Me; 3-Ph,5-H; 3-tBu,5-H). In
      the solid state, already the sterically least encumbered derivative L2(Me2) is
      able to stabilize Co(II) complexes of the form [X(2)Co(L2(Me2))] (X = Cl, NO(3));
      in solution, these complexes are at an equilibrium with the 1:2 species
      [Co(L2(Me2))(2)](2+). Oxidative demethylation of L3(Ph) and L3((t)Bu) with
      [Ce(NH(4))(2)(NO(3))(6)] leads to the corresponding para-benzoquinonyl
      substituted bis(pyrazol-1-yl)methane ligands L4(Ph) and L4((t)Bu). Contrary to
      that, the methyl derivative L3(Me2) is transformed into the ortho-benzoquinone
      species L5(Me2), which still contains one methoxy substituent while one oxygen
      atom has been newly introduced. The formation of L5(Me2) requires (i) the
      admission of air, (ii) the presence of both methoxy substituents of L3(Me2), and
      (iii) the presence of (methyl) substituents both at the exocyclic carbon atom and
      at the 5- positions of the pyrazolyl rings. The parent ortho-hydroquinonyl
      substituted bis(pyrazol-1-yl)methane ligand ((HO)(2)C(6)H(3))C(H)(pz(H,H))(2) is
      readily available from 3,4-dihydroxybenzaldehyde and (pz(H,H))(2)SO/pyridine.

PMID- 20690753
TI  - Crystal structure of a new polymorph of Li2FeSiO4.
AB  - We report on the crystal structure of a new polymorph of Li(2)FeSiO(4) (prepared
      by annealing under argon at 900 degrees C and quenching to 25 degrees C)
      characterized by electron microscopy and powder X-ray and neutron diffraction.
      The crystal structure of Li(2)FeSiO(4) quenched from 900 degrees C is
      isostructural with Li(2)CdSiO(4), described in the space group Pmnb with lattice
      parameters a = 6.2836(1) A, b = 10.6572(1) A, and c = 5.0386(1) A. A close
      comparison is made with the structure of Li(2)FeSiO(4) quenched from 700 degrees
      C, published recently by Nishimura et al. (J. Am. Chem. Soc. 2008, 130, 13212).
      The two polymorphs differ mainly on the respective orientations and alternate
      sequences of corner-sharing FeO(4) and SiO(4) tetrahedra.

PMID- 20690754
TI  - Vanadium diaminebis(phenolate) complexes: syntheses, structures, and reactivity
      in sulfoxidation catalysis.
AB  - Vanadium diaminebis(phenolate) complexes of the general formulas [LVCl(THF)] (L =
      Me(2)NCH(2)CH(R)N(CH(2)-2-O-3,5-C(6)H(2)(t)Bu(2))(2), where R = H, Me) and
      [LV(O)X] [X = Cl; R = H (2), Me (3), O(i)Pr (4), (mu-O)V(O)L (5)] are described.
      All compounds display octahedral geometry and trans-O(Ph) coordination. For
      compounds 2, 3, and 5, only one isomer, presenting the V=O ligand trans to the
      tripodal nitrogen, was formed, while for 4, two isomers were observed by NMR in
      solution. The UV-vis and circular dichroism spectra of 2 and 3 display very
      intense charge-transfer transition bands from the phenolate donors to the
      vanadium, which are in agreement with the (51)V low-field shifts observed. All
      vanadium(V) complexes were tested as thioanisole sulfoxidation catalysts,
      revealing very high selectivity when H(2)O(2) was used as the oxidant. However,
      no enantioselectivity was observed even when enantiopure 3 was used as the
      catalyst precursor. (1)H and (51)V NMR studies were conducted for the reactions
      of 2 with aqueous solutions of H(2)O(2) in methanol-d(4) and in acetonitrile
      d(3); 2 reacts with the solvents, leading to [LV(O)OMe], by replacement of Cl by
      MeO in methanol, and to a new vanadium aminebis(phenolate) complex, where the
      dimethylamine fragment of the original ligand L was replaced by CH(3)CN. In
      either case, (51)V NMR spectra suggest the formation of peroxovanadium species
      upon the addition of a H(2)O(2) solution. The subsequent addition of thioanisole
      to the methanol-d(4) solution leads to regeneration of the original complex.

PMID- 20690755
TI  - Fluorescence-based nitric oxide sensing by Cu(II) complexes that can be trapped
      in living cells.
AB  - A series of symmetrical, fluorescein-derived ligands appended with two
      derivatized 2-methyl-8-aminoquinolines were prepared and spectroscopically
      characterized. The ligands FL2, FL2E, and FL2A were designed to improve the
      dynamic range of previously described asymmetric systems, and the copper complex
      Cu(2)(FL2E) was constructed as a trappable NO probe that is hydrolyzed
      intracellularly to form Cu(2)(FL2A). The ligands themselves are only weakly
      emissive, and the completely quenched Cu(II) complexes, generated in situ by
      combining each ligand with 2 equiv of CuCl(2), were investigated as fluorescent
      probes for nitric oxide. Upon introduction of excess NO under anaerobic
      conditions to buffered solutions of Cu(2)(FL2), Cu(2)(FL2E), and Cu(2)(FL2A), the
      fluorescence increased by factors of 23 +/- 3, 17 +/- 2, and 27 +/- 3,
      respectively. The corresponding rate constants for fluorescence turn-on were
      determined to be 0.4 +/- 0.2, 0.35 +/- 0.05, and 0.6 +/- 0.1 min(-1). The probes
      are highly specific for NO over other biologically relevant reactive oxygen and
      nitrogen species, as well as Zn(II), the metal ion for which similar probes were
      designed to detect.

PMID- 20690756
TI  - A novel 1D-AF hybrid organic-inorganic chromium(II) methyl phosphonate dihydrate:
      synthesis, X-ray crystal and molecular structure, and magnetic properties.
AB  - Light-blue crystals of chromium(II) methyl phosphonate dihydrate,
      [Cr(CH(3)PO(3))(H(2)O)].H(2)O, were obtained in water by mixing filtered
      solutions of methylphosphonic acid and chromium(II) chloride in the presence of
      urea in an inert atmosphere. The compound was characterized by elemental
      analysis, TGA-DSC, X-ray crystallography, magnetic measurements, and UV-visible
      and FT-IR spectroscopies. The crystal and molecular structures (orthorhombic Pnma
      (no. 62): a = 4.4714(5) A, b = 6.8762(7) A, c = 19.180(2) A, Z = 4) have been
      solved using single-crystal X-ray diffraction. The chromium(II) ion is six
      coordinated by oxygens (4 + 2) to form an elongated octahedron, with the four
      equatorial oxygen atoms belonging to [-PO(3)](2-) phosphonate groups. This
      stereochemistry of the Cr(II) ion (high-spin d(4) electronic configuration) is
      ascribed to the Jahn-Teller effect. The [CrO(6)] chromophore, the [CH(3)PO(3)](2
      ) anions, and the water molecules build a novel one-dimensional (1D) metal(II)
      oxide chain, anchored to each other within the ab plane by two oxygens of the
      phosphonate ligand. Within the chain, each Cr(2+) ion is connected through double
      oxygen bridges to its two neighbors, forming edge-sharing octahedra running along
      the b axis. The chains are further connected with the adjacent chains by
      phosphonate [-PO(3)](2-) groups of the ligand, forming an inorganic layer that
      alternates along the c axis of the unit cell with bilayers, consisting of methyl
      groups and water of crystallization. The thermal variation of the magnetic
      susceptibility follows the Curie-Weiss law, with a large negative Weiss constant,
      theta = -60 K, indicating the presence of antiferromagnetic AF exchange
      interactions between neighboring Cr(II) ions. The magnetic behavior and the
      magnetic dimensionality have been analyzed in terms of Fisher's classical
      limiting form of the Heisenberg chain theory, and a value of J = -9.3 cm(-1) was
      found. The negative value of the intra-chain exchange constant coupling J
      confirms the presence of an AF coupling. No sign of long-range magnetic ordering
      down to 2 K (the lowest measured temperature) is observed, in agreement with the
      predominant one-dimensional character of the exchange interactions.

PMID- 20690757
TI  - Magnetic ordering in two molecule-based (10,3)-a nets prepared from a copper(II)
      trinuclear secondary building unit.
AB  - Two new molecule-based materials of formulas 3D-{[K(H(2)O)(6)](0.5)[K(18-crown
      6)](0.5)[MnCu(3)(Hmesox)(3)].5.25H(2)O} (1) and 3D
      {(Ph(4)P)(2)[MnCu(3)(Hmesox)(3)Cl].3.5H(2)O} (2) have been prepared from a
      tricopper(II) secondary building unit (SBU), [Cu(3)(Hmesox)(3)](3-) (H(4)mesox =
      mesoxalic acid, 2-dihydroxymalonic acid). Compound 1 is obtained by means of the
      reaction of the SBU with manganese(II) acetate in the presence of potassium
      cations and the 18-crown-6 ether, whereas compound 2 is obtained by means of the
      reaction of the SBU with manganese(II) acetate in the presence of Ph(4)PCl. The
      [MnCu(3)(Hmesox)(3)](-) and [MnCu(3)(Hmesox)(3)Cl](2-) moieties in compounds 1
      and 2, respectively, yield chiral 3-connected three-dimensional (3D) anionic
      (10,3)-a (srs, SrSi(2)) nets. In the cubic and centrosymmetric structures (Pa3)
      of 1, two inversion-symmetry-related anion nets interpenetrate to a racemic
      structure. The Ph(4)P(+) cations in 2 are organized in a supramolecular (10,3)-a
      net through the 6-fold phenyl embrace. In 2, both the cationic and anionic nets
      are homochiral and enantiopure with opposite handedness and form interpenetrating
      supramolecular and covalent (10,3)-a nets in the noncentrosymmetric Sohncke space
      group P 2(1)2(1)2(1). Both compounds display ferrimagnetic interaction with long
      range magnetic ordering below 2.5 and 15.2 K for 1 and 2, respectively. A
      dehydrated phase of 2 exhibits a T(c) of 21.8 K. The saturation of magnetization,
      M(S), indicates two different ground states, S = (1)/(2) and (3)/(2), for the
      tricopper(II) units in 1 and 2, respectively. The different spin states of the
      tricopper(II) unit in 1 and 2 has been explained by means of a density functional
      theory (DFT) study performed in the [Cu(3)(Hmesox)(3)](3-) and
      [Cu(3)(Hmesox)(3)Cl](4-) fragments, for 1 and 2, respectively. A further DFT
      study has allowed one to analyze the structural parameters that lead to the
      different spin ground states for the trinuclear units in both compounds.

PMID- 20690758
TI  - Synthesis, crystal and electronic structures, and physical properties of caged
      ternary Cu-rich antimonide: BaCu(7.31(3))Sb5.
AB  - A new caged Cu-rich antimonide, BaCu(7.31(3))Sb(5), was obtained from a direct
      combination of the elements in a graphite crucible under a high vacuum by a solid
      state reaction, and the structure was determined by the single-crystal X-ray
      diffraction method to be hexagonal P6(3)/mmc (No.194), with a = 7.0154(4) A, c =
      12.5423(14) A, V = 534.58(7) A(3), and Z = 2. BaCu(7.31(3))Sb(5) is the first
      antimonide member of the BaNi(9)P(5)-type barium copper pnictides with a Cu2 site
      occupancy of 43.7(9)%, and the structure building unit is a 30-vertex
      Cu(18)Sb(12) cage centered by a Ba atom. The Cu(18)Sb(12) cages form chains along
      the c axis by sharing the opposite hexagonal (Cu2)(3)(Sb2)(3) faces. Such a cage
      chain shares (Cu1)(2)(Sb1)(2) rhomboidal faces with six neighboring chains along
      the [100], [010], and [110] directions to generate a 3D condensed metallic
      network. The electronic structure calculations by CASTEP indicate the metallic
      nature, which matches well with the metallic electrical conductivity, small
      Seebeck coefficient, and Pauli paramagnetism. The calculated formation energies
      indicate that BaCu(7.5)Sb(5)[triple bond]Ba(2)Cu(15)Sb(10) with the Cu2 site half
      occupied is the energetically favorable stoichiometry compared with
      Ba(2)Cu(12)Sb(10) (empty Cu2 site) and Ba(2)Cu(18)Sb(10) (fully occupied Cu2
      site).

PMID- 20690759
TI  - Long-range electronic communication in free-base meso-poly(ferrocenyl)-containing
      porphyrins.
AB  - H(2)FcPh(3)P [FcPh(3)P = 5-ferrocenyl-10,15,20-triphenyl porphyrin(2-)], cis
      H(2)Fc(2)Ph(2)P [cis-Fc(2)Ph(2)P = 5,10-bisferrocenyl-15,20-diphenyl porphyrin(2
      )], trans-H(2)Fc(2)Ph(2)P [trans-Fc(2)Ph(2)P = 5,15-bisferrocenyl-10,20-diphenyl
      porphyrin(2-)], and H(2)Fc(3)PhP [Fc(3)PhP = 5,10,15-trisferrocenyl-20-phenyl
      porphyrin(2-)] along with H(2)TPP [TPP = 5,10,15,20-tetraphenylporphyrin] and
      H(2)TFcP [TFcP = 5,10,15,20-tetraferrocenyl porphyrin(2-)] were isolated from the
      direct cross-condensation reaction between pyrrole, benzaldehyde, and ferrocene
      carboxaldehyde or from the reaction between ferrocenyl-2,2'-dipyrromethane and
      benzaldehyde, suggesting a scrambling reaction mechanism for the last approach.
      All compounds were characterized by UV-vis, MCD, and NMR spectroscopy; APCI MS
      and MS/MS methods; as well as high-resolution ESI MS spectrometry. The
      conformational flexibility of ferrocene substituents in all compounds was
      confirmed using variable-temperature NMR and computational methods. DFT
      calculations were employed to understand the degree of nonplanarity of the
      porphyrin core as well as the electronic structure of ferrocene-containing
      porphyrins. In all cases, a set of occupied, predominantly ferrocene-based
      molecular orbitals was found between the highest occupied and the lowest
      unoccupied, predominantly porphyrin-based molecular pi orbitals. The redox
      properties of all ferrocene-containing porphyrins were investigated in a
      CH(2)Cl(2)/TFAB [TFAB = tetrabutylammonium tetrakis(perfluorophenyl)borate]
      system using cyclic voltammetry, differential pulse voltammetry, and square wave
      voltammetry methods. In all cases, oxidations of individual ferrocene
      substituent(s) along with porphyrin core oxidation(s) and reductions have been
      observed. Mixed-valence [cis-H(2)Fc(2)Ph(2)P](+), [trans-H(2)Fc(2)Ph(2)P](+),
      [H(2)Fc(3)PhP](+), and [H(2)Fc(3)PhP](2+) complexes were formed in situ under
      spectroelectrochemical and chemical oxidation conditions and were characterized
      using UV-vis and MCD approaches. Analysis of intervalence charge-transfer bands
      observed in the NIR region for all mixed-valence complexes suggests electron
      localization and thus class II behavior in the Robin-Day classification.

PMID- 20690760
TI  - Sulfur-containing mixed-donor tribenzo-macrocycles and their endo- and exocyclic
      supramolecular silver(I) and copper(I) complexes.
AB  - New sulfur-containing mixed-donor macrocycles L(1)-L(4) with different donor sets
      and/or ring sizes (L(1), 20-membered O(3)S(2); L(2), 20-membered NO(2)S(2); L(3),
      20-membered O(2)S(3); and L(4), 23-membered O(4)S(2)) were synthesized and
      structurally characterized by X-ray analysis. A comparative investigation of the
      coordination behavior of these macrocyclic ligands with silver(I) salts and
      copper(I) iodide is reported. The X-ray structures of seven complexes (1-7) have
      been determined, and a range of structural types and coordination modes,
      including mono- to multinuclear and endo- to exocyclic ones via M-S bonds, is
      shown to occur. In all seven complexes, the ether oxygens of each ring are
      unbound. Reactions of L(1)-L(4) with the silver(I) salts (ClO(4)(-), BF(4)(-),
      and NO(3)(-)) afforded four complexes with different topologies: the exocyclic 1
      D coordination polymer [Ag(L(1))(ClO(4))](n) (1), the endocyclic 1:1 monomer
      complex [Ag(L(2))]ClO(4).CH(3)OH (2), the endo-/exocyclic 1-D coordination
      polymer {[Ag(2)(L(2))(CH(3)OH)](BF(4))(2)}(n) (3), and the cyclic dimer complex
      [Ag(2)(L(3))(2)(NO(3))(2)].2CH(3)CN (4). NMR titrations of L(1) and L(2) with
      silver(I) perchlorate were carried out to explore their complexation behavior in
      solution and also for comparison with the solid state structures. As well,
      reaction of the above ligands with copper(I) iodide afforded the exocyclic dimer,
      [Cu(2)I(2)(L(1))(2)].CH(2)Cl(2) (5), linked with diamond-type Cu-I(2)-Cu unit,
      the exocyclic monomer complex [CuI(L(3))].CH(2)Cl(2) (6), and the emissive 1-D
      poly(cyclic dimer) complex {[Cu(4)I(4)(L(4))(2)].CH(2)Cl(2)}(n) (7) linked by a
      cubane-type Cu(4)I(4) unit. The formation of both the discrete and continuous
      supramolecular complexes with copper(I) iodide is discussed in terms of a ligand
      directed "sulfur-to-sulfur" distance effect.

PMID- 20690761
TI  - Transition metal complexes supported by a neutral tetraamine ligand containing
      N,N-dimethylaniline units.
AB  - First-row transition metal-halide complexes of tris(2-dimethylaminophenyl)amine,
      L(Me), have been synthesized and characterized. X-ray crystallographic studies on
      [Co(L(Me))Br]BPh(4), [Ni(L(Me))Cl]BPh(4), [Fe(L(Me))Cl]BPh(4), and
      [Cu(L(Me))Cl]BF(4) have been performed, and in all cases the ligand produces five
      coordinate complexes with distorted trigonal bipyramidal coordination geometries.
      Where possible, comparisons have been made to the structures of related neutral
      tripodal ligands. Spectroscopic and magnetic studies of these complexes are also
      described. The Cu(I)-carbonyl complexes [Cu(L(Me))(CO)]PF(6) and
      [Cu(Me(6)tren)(CO)]PF(6) (Me(6)tren = tris(N,N-dimethylaminoethyl)amine) have
      also been prepared. Infrared spectroscopic investigations of these carbonyl
      complexes confirm that L(Me) is a less electron donating ligand than Me(6)tren
      and indicate that L(Me) can impart a different coordination number in the solid
      state.

PMID- 20690762
TI  - Oxo- and hydroxomanganese(IV) adducts: a comparative spectroscopic and
      computational study.
AB  - The electronic structures of the bis(hydroxo)manganese(IV) and
      oxohydroxomanganese(IV) complexes [Mn(IV)(OH)(2)(Me(2)EBC)](2+) and
      [Mn(IV)(O)(OH)(Me(2)EBC)](+) were probed using electronic absorption, magnetic
      circular dichroism (MCD), and variable-temperature, variable-field MCD
      spectroscopies. The d-d transitions of [Mn(IV)(OH)(2)(Me(2)EBC)](2+) were
      assigned using a group theory analysis coupled with the results of time-dependent
      density functional theory computations. These assignments permit the development
      of an experimentally validated description for the pi and sigma interactions in
      this complex. A similar analysis performed for [Mn(IV)(O)(OH)(Me(2)EBC)](+)
      reveals that there is a significant increase in the ligand character in the Mn
      pi* orbitals for the Mn(IV)=O complex relative to the bis(hydroxo)manganese(IV)
      complex, whereas the compositions of the Mn sigma* orbitals are less affected.
      Because of the steric features of the Me(2)EBC ligand, we propose that H-atom
      transfer by these reagents proceeds via the sigma* orbitals, which, because of
      their similar compositions among these two compounds, leads to modest rate
      enhancements for the Mn(IV)=O versus Mn(IV)OH species.

PMID- 20690763
TI  - Structural characterization of zinc and iron (II/III) complexes of a porphyrin
      bearing two built-in nitrogen bases. An example of high-spin diaqua-iron(III)
      bromo complex.
AB  - A bis-strapped porphyrin with two intramolecular nitrogen bases was synthesized,
      and its zinc(II), iron(II), and iron(III) complexes have been structurally
      characterized. Whereas the zinc(II) complex is square pyramidal five-coordinate
      and the iron(II) complex is six-coordinate despite a significant distortion of
      the macrocycle induced by the rigidity of the straps, the iron(III) complex
      exhibits a peculiar bis-aqua structure in which no intramolecular axial base is
      bound to the iron atom in the porphyrin. Furthermore, on one side, the bromide
      counteranion of the iron is bound inside the cycle formed by a strap and
      establishes a hydrogen bond with an axially bound water molecule. On the other
      side, a residual HBr molecule protonates one pyridine base leading to the
      formation of an intermolecular pyridinium-pyridine hydrogen bond. The large ionic
      radius of the high-spin iron(III) cation is accommodated in the macrocycle with
      no displacement of the metal out of the mean porphyrinic plane, with an average
      Fe-Np bond distance of 2.057 A, and the axial Fe-Ow(aqua) bond distance measured
      at 2.090 A. As a result, this high-spin iron(III) bis-aqua complex is only
      lightly distorted.

PMID- 20690764
TI  - Theoretical analysis of the spin exchange and magnetic dipole-dipole interactions
      leading to the magnetic structure of Ni3TeO6.
AB  - The origin of the collinear antiferromagnetic magnetic structure of Ni(3)TeO(6)
      below 52 K was analyzed by calculating its spin exchanges on the basis of density
      functional calculations, and the cause for the parallelc-spin orientation found
      for this magnetic structure by calculating the spin-orbit coupling and magnetic
      dipole-dipole interaction energies. The calculated exchanges correctly predict
      the observed magnetic structure below 52 K, and lead practically to no spin
      frustration. The perpendicularc- and parallelc-spin orientations are predicted by
      the spin-orbit coupling and the magnetic dipole-dipole interactions,
      respectively. However, the magnetic dipole-dipole interactions are stronger than
      the spin-orbit coupling interactions, and hence are responsible for the spin
      orientation observed for Ni(3)TeO(6).

PMID- 20690765
TI  - Magnetic properties of dysprosium cubanes dictated by the M-O-M angles of the
      [Dy4(mu3-OH)4] core.
AB  - Two new dysprosium(III) coordination compounds, namely,
      [Dy(4)(HL)(4)(C(6)H(4)NH(2)COO)(2)(mu(3)-OH)(4)(mu
      OH)(2)(H(2)O)(4)].4CH(3)CN.12H(2)O (1) and
      Dy(8)(HL)(10)(C(6)H(4)NH(2)COO)(2)(mu(3)-OH)(8)(OH)(2)(NO(3))(2)(H(2)O)(4)] (2),
      have been synthesized from the Schiff-base ligand 2-{[(2-hydroxy-3
      methoxyphenyl)methylidene]amino}benzoic acid (H(2)L) and dysprosium chloride (1)
      or dysprosium nitrate (2). Single-crystal X-ray diffraction studies reveal that
      compound 1 exhibits a tetranuclear cubane-like structure and that 2 is an
      octanuclear, bis-cubane complex. The [Dy(4)(mu (3)-OH)(4)] cubane cores of 1 and
      2 are structurally related; however, the magnetic properties of 1 and 2 are
      drastically different. Indeed, 2 shows slow relaxation of magnetization while no
      out-of-phase alternating current (ac) signal is noticed for 1. These significant
      disparities are most likely due to the different M-O-M angles observed for the
      respective cubane cores.

PMID- 20690766
TI  - Heterospin pi-heterocyclic radical-anion salt: synthesis, structure, and magnetic
      properties of decamethylchromocenium [1,2,5]thiadiazolo[3,4
      c][1,2,5]thiadiazolidyl.
AB  - Decamethylchromocene, Cr(II)(eta(5)-C(5)(CH(3))(5))(2) (2), readily reduced
      [1,2,5]thiadiazolo[3,4-c][1,2,5]thiadiazole (1) in a tetrahydrofuran solvent at
      ambient temperature with the formation of radical-anion salt [2](+)[1](-) (3)
      isolated in 97% yield. The heterospin salt 3 ([2](+), S = 3/2; [1](-), S = 1/2)
      was characterized by single-crystal X-ray diffraction as well as magnetic
      susceptibility measurements in the temperature range 2-300 K. The experimental
      data together with theoretical analysis of the salt's magnetic structure within
      the CASSCF and spin-unrestricted broken-symmetry (BS) density functional theory
      (DFT) approaches revealed antiferromagnetic (AF) interactions in the crystalline
      3: significant between anions [1](-), weak between cations [2](+), and very weak
      between [1](-) and [2](+). Experimental temperature dependences of the magnetic
      susceptibility and the effective magnetic moment of 3 were very well reproduced
      in the assumption of the AF-coupled [1](-)...[1](-) (J(1) = -40 +/- 9 cm(-1)) and
      [2](+)...[2](+) (J(2) = -0.58 +/- 0.03 cm(-1)) pairs. The experimental J(1) value
      is in reasonable agreement with the value calculated using BS UB3LYP/6-31+G(d) (
      61 cm(-1)) and CASSCF(10,10)/6-31+G(d) (-15.3 cm(-1)) approaches. The
      experimental J(2) value is also in agreement with that calculated using the BS
      DFT approach (-0.33 cm(-1)).

PMID- 20690767
TI  - Nature of magnetic interactions in 3D {[M(II)(pyrazole)4]2[Nb(IV)(CN)8].4H2O}n (M
      = Mn, Fe, Co, Ni) molecular magnets.
AB  - The self-assembly of [Nb(IV)(CN)(8)](4-) with different 3d metal centers in an
      aqueous solution and an excess of pyrazole resulted in the formation of four 3D
      isostructural compounds {[M(II)(pyrazole)(4)](2)[Nb(IV)(CN)(8)].4H(2)O}(n), where
      M(II) = Mn, Fe, Co, and Ni for 1-4, respectively. All four assemblies crystallize
      in the same I4(1)/a space group and show identical cyanido-bridged structures
      decorated with pyrazole molecules coordinated to M(II) centers. All four
      compounds show also long-range magnetic ordering below 24, 8, 6, and 13 K,
      respectively. A thorough analysis of the structural and magnetic data utilizing
      the molecular field model has allowed for an estimation of the values of coupling
      constants J(M-Nb) attributed to the one type of M(II)-NC-Nb(IV) linkage existing
      in 1-4. The J(M-Nb) values increase monotonically from -6.8 for 1 through -3.1
      for 2 and +3.5 for 3, to +8.1 cm(-1) for 4 and are strongly correlated with the
      number of unpaired electrons on the M(II) metal center. Average orbital
      contributions to the total exchange coupling constants J(M-Nb) have also been
      identified and calculated: antiferromagnetic J(AF) = -21.6 cm(-1) originating
      from the d(xy), d(xz), and d(yz) orbitals of M(II) and ferromagnetic J(F) = +15.4
      cm(-1) originating from d(z(2)) and d(x(2)-y(2)) orbitals of M(II).
      Antiferromagnetic interaction is successively weakened in the 1-4 row with each
      additional electron on the t(2g) level, which results in a change of the sign of
      J(M-Nb) and the nature of long-range magnetic ordering from ferrimagnetic in 1
      and 2 to ferromagnetic in 3 and 4.

PMID- 20690768
TI  - Hypervalent adducts of chalcogen-containing peri-substituted naphthalenes;
      reactions of sulfur, selenium, and tellurium with dihalogens.
AB  - A range of structurally diverse compounds 1-15 {Nap[SPh](2).Br(4) (Nap =
      naphthalene-1,8-diyl); Nap[SePh][EPh].Br(4) (E = Se, S); Nap[SePh](2).I(2);
      Nap[SePh][EPh].3/2I(2) (E = Se, S); Nap[TePh][G].X(2) (G = SePh, SPh, Br, I; X =
      Br, I); and [Nap(PPh(2)OH)(SPh)](+)Br(3)(-)} formed from the reactions between
      peri-substituted naphthalene chalcogen donors D1-D8 {Nap[ER][E'R] (ER/E'R = SPh,
      SePh, TePh); Nap[TePh][X] (X = Br, I); and Nap[PPh(2)][SPh]} and dibromine and
      diiodine were characterized by X-ray crystallography and where possible by
      multinuclear NMR, IR, and MS. X-ray data for 1-15 were analyzed by naphthalene
      ring torsions, peri-atom displacement, splay angle magnitude, peri-distance,
      aromatic ring orientations, and quasi-linear three-body arrangements. The
      hypervalent linear moieties are considered in the context of the charge-transfer
      model and the 3c-4e model introduced by Pimentel and Rundle. In general, the
      conformation of the final products obeyed the rule based on charge-transfer that
      "seesaw" (X-ER(2)-X, 10-E-4) adducts arise when the halogen (X) is more
      electronegative than the chalcogen (E), and if the converse is true then, CT
      "spoke" (X-X-ER(2), 8-E-3) adducts are formed. Upon treatment with dibromine,
      selenium donor compounds D2 {Nap[SePh](2)} and D3 {Nap[SePh][SPh]} afford unusual
      tribromide salts of bromoselenyl cations containing a hypervalent X-E...E' 3c-4e
      type interaction. Upon treatment with diiodine, D2 and D3 form "Z-shaped",
      "extended spoke" adducts containing an uncommon 2:3 donor/chalcogen ratio and
      incorporating chains of I(2) held together by rare I...I interactions. As
      expected, "seesaw" 10-E-4 adducts are formed following the reaction of Te donors
      D4-D7 {Nap[TePh][X] (X = Br, I); Nap[TePh][EPh] (E = Se, S)} with the dihalogens.
      Naphthalene distortion in general is comparable between respective donor
      compounds and products 1-15. Ionic species 2 and 3 display a noticeable reduction
      in molecular distortion explained by the relief of steric strain via weak peri
      interactions and the onset of 3c-4e bonding.

PMID- 20690769
TI  - Ligand substitution from the (eta5-DMP)Mn(CO)2(Solv) [DMP = 2,5-dimethylpyrrole,
      Solv = solvent] complexes: to ring slip or not to ring slip?
AB  - The mechanism and energetics of the displacement of solvent from photolytically
      generated (eta(5)-DMP)Mn(CO)(2)(Solv) complexes has been studied [DMP = 2,5
      dimethylpyrrole, Solv = solvent]. Rate enhancement relative to the eta(5)
      cyclopentadienyl (Cp) system is not observed in the displacement of weakly bound
      solvents. The bond dissociation enthalpies obtained from the kinetic analysis are
      in good agreement with the values obtained by detailed density functional theory
      (DFT) calculations. The results indicate that for both the Cp and the DMP based
      systems the displacement of weakly bound solvents proceeds by a dissociative or
      I(d) mechanism. This is in sharp contrast to CO displacement from (eta(5)
      DMP)Mn(CO)(3), which is known to proceed by an associative mechanism by way of an
      eta(3) ring slip intermediate. The associative substitution pathway only becomes
      competitive with the dissociative channel when the Mn-Solv bond dissociation
      enthalpy is more than 33 kcal/mol.

PMID- 20690770
TI  - Serum metabolic signature of minimal hepatic encephalopathy by (1)H-nuclear
      magnetic resonance.
AB  - Minimal hepatic encephalopathy (MHE) reduces quality of life of cirrhotic
      patients, predicts overt hepatic encephalopathy, and is associated with poor
      prognosis. We hypothesized that MHE arises once metabolic alterations derived
      from the liver reach a particular threshold. Our aim was to assess whether
      metabolic profiling of serum samples by high-field (1)H-nuclear magnetic
      resonance spectroscopy ((1)H NMR) and subsequent multivariate analyses would be
      useful to characterize metabolic perturbations associated with MHE and to
      identify potential metabolic biomarkers. Metabolic serum profiles from controls
      (n = 69) and cirrhotic patients without MHE (n = 62) and with MHE (n = 39) were
      acquired using high field NMR. Supervised modeling of the data provided perfect
      discrimination between healthy controls and cirrhotic patients and allowed the
      generation of a predictive model displaying strong discrimination between
      patients with and without MHE (R(2)Y = 0.68, Q(2)Y = 0.63). MHE patients
      displayed increased serum concentrations of glucose, lactate, methionine, TMAO,
      and glycerol, as well as decreased levels of choline, branch amino acids,
      alanine, glycine, acetoacetate, NAC, and lipid moieties. Serum metabonomics by
      (1)H NMR offers a useful approach for characterizing underlying metabolic
      differences between patients with and without MHE. This procedure shows great
      potential as a diagnostic tool of MHE as it objectively reflects measurable
      biochemical differences between the patient groups and may facilitate monitoring
      of both disease progression and effects of therapeutic treatments.

PMID- 20690771
TI  - A nanoscale interface improves attachment of cast polymers to glass.
AB  - A novel interface was prepared on glass slides that stabilizes several cast
      polymers against delamination under conditions necessary for the study of cell
      surface interactions. This interface was synthesized by deposition of zirconium
      tetra(tert-butoxide) from the vapor phase onto the glass followed by mild
      thermolysis, which gives a surface-bound zirconium oxide coating. This oxide
      coating improved attachment of polymer coatings cast from formic acid or
      methylene chloride. Nylon, polyurethane, and
      polyhydroxybutyrate/polyhydroxyvalerate coatings were stable against delamination
      from the oxide-coated glass following sonication in ethanol for more than 30 min
      or immersion in water at pH 8 for at least 48 h.

PMID- 20690773
TI  - Submicrometer aluminum spheres' adhesion to planar silicon substrates.
AB  - We investigate the adhesion mechanism of aluminum spheres on a silicon substrate.
      Aluminum particles in the size range of 60-1500 nm were deposited onto a silicon
      substrate. It was found that aluminum particles underwent plastic deformation
      rather than elastic deformation because of van der Waals interactions. A finite
      element model developed recently is also used to analyze our results. Because the
      MP model was proposed to describe plastic deformation based on an analysis of
      metal microcontacts, our results prove the correctness of the MP model from its
      origin and basis of arguments.

PMID- 20690772
TI  - Capacitive monitoring of morpholino-DNA surface hybridization: experimental and
      theoretical analysis.
AB  - Impedance and cyclic voltammetry methods, complemented by Poisson-Boltzmann (PB)
      modeling, are used to study hybridization of DNA analyte strands to monolayers of
      morpholino oligomers (MOs) immobilized by one end to mercaptopropanol-passivated
      gold electrodes. MOs, like peptide nucleic acids (PNAs), are uncharged molecules
      that recognize nucleic acids following conventional base-pairing rules. The
      capacitive response to hybridization, determined from real-time impedance
      measurements, is analyzed with emphasis on understanding the underlying
      structural changes and on providing a foundation for label-free diagnostics. The
      capacitive response is correlated with the instantaneous surface molecular
      populations by labeling DNA and MO strands with ferrocene tags and using cyclic
      voltammetry to monitor their respective coverages in real-time. This approach
      allows analysis of hybridization-induced changes in interfacial capacitance as a
      function of duplex coverage, the DC bias used for readout, buffer molarity, and
      probe coverage. The results indicate that unhybridized MO layers exist in a
      compact state on the solid support. For hybridized layers, the intrinsic signal
      per hybridization event is strongly enhanced at low ionic strengths but,
      interestingly, does not depend on the readout bias in the sampled range negative
      of the capacitive minimum. A PB model incorporating an effective medium
      description of the hybridizing films is used to establish how hybridization
      derived changes in dielectric composition and charge distribution at the surface
      translate into experimentally observed variations in interfacial capacitance.

PMID- 20690774
TI  - Atropisomeric properties of 7-, 8-, and 9-membered-ring dibenzolactams:
      conformation, thermal stability, and chemical reactivity.
AB  - The atropisomeric enantiomers of 7-, 8-, and 9-membered-ring dibenzolactams were
      separated by using chiral HPLC, and their stereochemistries were clarified by
      using X-ray crystallographic analysis. The atropisomers showed high
      stereochemical stability with the 8-membered ring being the most stable. In 7-
      and 8-membered dibenzolactams, highly stereoselective C7-methylation proceeded
      from the lower side of the ring to provide the products with a C7-methyl group in
      the pseudoaxial orientation, which converted to thermodynamically more stable
      isomers with the pseudoequatorial C7-methyl group. In 9-membered dibenzolactam,
      C7-methylation occurred from the opposite (upper) side of the ring to provide a
      thermodynamically stable product with the pseudoequatorial C7-methyl group.

PMID- 20690775
TI  - Synthesis and functionalization of asymmetrical benzo-fused BODIPY dyes.
AB  - A series of asymmetrical benzo-fused BODIPY dyes were synthesized from the
      Sonogashira coupling and nucleophilic substitution reactions on the 3-halogenated
      benzo-fused BODIPY, generated from readily available 3-halogeno-1
      formylisoindoles in a two-step synthetic procedure. This novel BODIPY platform
      provides an easy path for the linking of BODIPY fluorophore to various desired
      functionalities as demonstrated in this work. Most of the resulting BODIPY dyes
      show long-wavelength absorption and fluorescence emission, with good fluorescence
      quantum yields and long fluorescence lifetimes.

PMID- 20690776
TI  - Practical enantiospecific synthesis of an orthogonally protected 1,4-trans-1,5
      cis- 4,5-diamino-2-cyclopenten-1-ol derivative.
AB  - An enantiospecific synthesis of an orthogonally protected 1,4-trans-1,5-cis-4,5
      diamino-2-cyclopenten-1-ol derivative 16 is reported. The trans-diamine moiety
      was established by anti-specific vinyl addition to a novel threitol-derived tert
      butanesulfinylimine 2 and Overman rearrangement. The cyclopentene skeleton was
      constructed via RCM reaction of a key 1,6-diene intermediate 11.

PMID- 20690777
TI  - On-road vehicle emission control in Beijing: past, present, and future.
AB  - Beijing, the capital of China, has experienced rapid motorization since 1990; a
      trend that is likely to continue. The growth in vehicles and the corresponding
      emissions create challenges to improving the urban air quality. In an effort to
      reduce the impact of vehicle emissions on urban air quality, Beijing has adopted
      a number of vehicle emission control strategies and policies since the mid 1990
      s. These are classified into seven categories: (1) emission control on new
      vehicles; (2) emission control on in-use vehicles; (3) fuel quality improvements;
      (4) alternative-fuel and advanced vehicles; (5) economic policies; (6) public
      transport; and (7) temporal traffic control measures. Many have proven to be
      successful, such as the Euro emission standards, unleaded gasoline and low sulfur
      fuel, temporal traffic control measures during the Beijing Olympic Games, etc.
      Some, however, have been failures, such as the gasoline-to-LPG taxi retrofit
      program. Thanks to the emission standards for new vehicles as well as other
      controls, the fleet-average emission rates of CO, HC, NO(X), and PM(10) by each
      major vehicle category are decreasing over time. For example, gasoline cars
      decreased fleet-average emission factors by 12.5% for CO, 10.0% for HC, 5.8% for
      NO(X), and 13.0% for PM(10) annually since 1995, and such a trend is likely to
      continue. Total emissions for Beijing's vehicle fleet increased from 1995 to
      1998. However, they show a clear and steady decrease between 1999 and 2009. In
      2009, total emissions of CO, HC, NO(X), and PM(10) were 845,000 t, 121,000 t,
      84,000 t, and 3700 t, respectively; with reductions of 47%, 49%, 47%, and 42%,
      relative to 1998. Beijing has been considered a pioneer in controlling vehicle
      emissions within China, similar to the role of California to the U.S. The
      continued rapid growth of vehicles, however, is challenging Beijing's policy
      makers.

PMID- 20690778
TI  - Structure-based interpretation of biotransformation pathways of amide-containing
      compounds in sludge-seeded bioreactors.
AB  - Partial microbial degradation of xenobiotic compounds in wastewater treatment
      plants (WWTPs) results in the formation of transformation products, which have
      been shown to be released and detectable in surface waters. Rule-based systems to
      predict the structures of microbial transformation products often fail to
      discriminate between alternate transformation pathways because structural
      influences on enzyme-catalyzed reactions in complex environmental systems are not
      well understood. The amide functional group is one such common substructure of
      xenobiotic compounds that may be transformed through alternate transformation
      pathways. The objective of this work was to generate a self-consistent set of
      biotransformation data for amide-containing compounds and to develop a metabolic
      logic that describes the preferred biotransformation pathways of these compounds
      as a function of structural and electronic descriptors. We generated
      transformation products of 30 amide-containing compounds in sludge-seeded
      bioreactors and identified them by means of HPLC-linear ion trap-orbitrap mass
      spectrometry. Observed biotransformation reactions included amide hydrolysis and
      N-dealkylation, hydroxylation, oxidation, ester hydrolysis, dehalogenation, nitro
      reduction, and glutathione conjugation. Structure-based interpretation of the
      results allowed for identification of preferences in biotransformation pathways
      of amides: primary amides hydrolyzed rapidly; secondary amides hydrolyzed at
      rates influenced by steric effects; tertiary amides were N-dealkylated unless
      specific structural moieties were present that supported other more readily
      enzyme-catalyzed reactions. The results allowed for the derivation of a metabolic
      logic that could be used to refine rule-based biotransformation pathway
      prediction systems to more specifically predict biotransformations of amide
      containing compounds.

PMID- 20690779
TI  - Fluorescent ribonucleoside as a FRET acceptor for tryptophan in native proteins.
AB  - A new fluorescent ribonucleoside analogue, containing 5-aminoquinazoline
      2,4(1H,3H)-dione, acts as a Forster resonance energy transfer acceptor for
      tryptophan (R(0) = 22 A) and displays visible emission (440 nm). As tryptophan is
      frequently found at or near the recognition domains of RNA binding proteins, this
      FRET pair facilitates the study of RNA binding to native proteins and peptides,
      which is demonstrated here for the HIV-1 Rev association with the Rev Response
      Element (RRE).

PMID- 20690780
TI  - Routine plasma anti-Xa monitoring is required for low-molecular-weight heparins.
AB  - Low-molecular-weight heparins are anticoagulants used in the treatment of
      thrombosis. They have effectiveness and safety profiles similar to those of
      unfractionated heparin but are considered an attractive alternative because of
      their predictable pharmacokinetic characteristics. In this article, we
      demonstrate the need for therapeutic monitoring of low-molecular-weight heparins
      by addressing evidence arising from the literature and from modelling and
      simulation. First, treatment targets for unfractionated heparin and enoxaparin
      sodium were identified. Then, 10 000 virtual patients were simulated and the rate
      of treatment success was calculated. Treatment success was found to be similar
      between the two drugs (48% with unfractionated heparin and 54% with enoxaparin
      sodium). These results are consistent with empirical evidence from the literature
      and reflect the inadequacy of current dosing strategies in achieving desired
      biomarker targets. These results, along with recent advances in Bayesian
      forecasting techniques, support the need for routine monitoring and dose
      individualization of enoxaparin sodium in order to improve treatment success.

PMID- 20690781
TI  - Dipeptidylpeptidase-4 inhibitors (gliptins): focus on drug-drug interactions.
AB  - Patients with type 2 diabetes mellitus (T2DM) are generally treated with many
      pharmacological compounds and are exposed to a high risk of drug-drug
      interactions. Indeed, blood glucose control usually requires a combination of
      various glucose-lowering agents, and the recommended global approach to reduce
      overall cardiovascular risk generally implies administration of several
      protective compounds, including HMG-CoA reductase inhibitors (statins),
      antihypertensive compounds and antiplatelet agents. New compounds have been
      developed to improve glucose-induced beta-cell secretion and glucose control,
      without inducing hypoglycaemia or weight gain, in patients with T2DM.
      Dipeptidylpeptidase-4 (DPP-4) inhibitors are novel oral glucose-lowering agents,
      which may be used as monotherapy or in combination with other antidiabetic
      compounds, metformin, thiazolidinediones or even sulfonylureas. Sitagliptin,
      vildagliptin and saxagliptin are already on the market, either as single agents
      or in fixed-dose combined formulations with metformin. Other compounds, such as
      alogliptin and linagliptin, are in a late phase of development. This review
      summarizes the available data on drug-drug interactions reported in the
      literature for these five DDP-4 inhibitors: sitagliptin, vildagliptin,
      saxagliptin, alogliptin and linagliptin. Possible pharmacokinetic interferences
      have been investigated between each of these compounds and various
      pharmacological agents, which were selected because there are other glucose
      lowering agents (metformin, glibenclamide [glyburide],
      pioglitazone/rosiglitazone) that may be prescribed in combination with DPP-4
      inhibitors, other drugs that are currently used in patients with T2DM (statins,
      antihypertensive agents), compounds that are known to interfere with the
      cytochrome P450 (CYP) system (ketoconazole, diltiazem, rifampicin [rifampin]) or
      with P-glycoprotein transport (ciclosporin), or agents with a narrow therapeutic
      safety window (warfarin, digoxin). Generally speaking, almost no drug-drug
      interactions or only minor drug-drug interactions have been reported between DPP
      4 inhibitors and any of these drugs. The gliptins do not significantly modify the
      pharmacokinetic profile and exposure of the other tested drugs, and the other
      drugs do not significantly alter the pharmacokinetic profile of the gliptins or
      exposure to these. The only exception concerns saxagliptin, which is metabolized
      to an active metabolite by CYP3A4/5. Therefore, exposure to saxagliptin and its
      primary metabolite may be significantly modified when saxagliptin is
      coadministered with specific strong inhibitors (ketoconazole, diltiazem) or
      inducers (rifampicin) of CYP3A4/5 isoforms. The absence of significant drug-drug
      interactions could be explained by the favourable pharmacokinetic characteristics
      of DPP-4 inhibitors, which are not inducers or inhibitors of CYP isoforms and are
      not bound to plasma proteins to a great extent. Therefore, according to these
      pharmacokinetic findings, which were generally obtained in healthy young male
      subjects, no dosage adjustment is recommended when gliptins are combined with
      other pharmacological agents in patients with T2DM, with the exception of a
      reduction in the daily dosage of saxagliptin when this drug is used in
      association with a strong inhibitor of CYP3A4/A5. It is worth noting, however,
      that a reduction in the dose of sulfonylureas is usually recommended when a DPP-4
      inhibitor is added, because of a pharmacodynamic interaction (rather than a
      pharmacokinetic interaction) between the sulfonylurea and the DPP-4 inhibitor,
      which may result in a higher risk of hypoglycaemia. Otherwise, any gliptin may be
      combined with metformin or a thiazolidinedione (pioglitazone, rosiglitazone),
      leading to a significant improvement in glycaemic control without an increased
      risk of hypoglycaemia or any other adverse event in patients with T2DM. Finally,
      the absence of drug-drug interactions in clinical trials in healthy subjects
      requires further evidence from large-scale studies, including typical subjects
      with T2DM - in particular, multimorbid and geriatric patients receiving
      polypharmacy.

PMID- 20690782
TI  - Population pharmacokinetic modelling of roflumilast and roflumilast N-oxide by
      total phosphodiesterase-4 inhibitory activity and development of a population
      pharmacodynamic-adverse event model.
AB  - BACKGROUND: Roflumilast is an oral, selective phosphodiesterase (PDE)-4 inhibitor
      in development for the treatment of chronic obstructive pulmonary disease (COPD).
      Both roflumilast and its metabolite roflumilast N-oxide have anti-inflammatory
      properties that contribute to overall pharmacological activity. OBJECTIVES: To
      model the pharmacokinetics of roflumilast and roflumilast N-oxide, evaluate the
      influence of potential covariates, use the total PDE4 inhibitory activity
      (tPDE4i) concept to estimate the combined inhibition of PDE4 by roflumilast and
      roflumilast N-oxide, and use individual estimates of tPDE4i to predict the
      occurrence of adverse events (AEs) in patients with moderate-to-severe COPD.
      METHODS: We modelled exposure to roflumilast and roflumilast N-oxide (21 studies
      provided the index dataset and five separate studies provided the validation
      dataset), extended the models to COPD (using data from two studies) and assessed
      the robustness of the parameter estimates. A parametric bootstrap estimation was
      used to quantify tPDE4i in subpopulations. We established logistic regression
      models for each AE occurring in >2% of patients in a placebo-controlled trial
      that achieved a p-value of <0.2 in a permutation test. The exposure variables
      were the area under the plasma concentration-time curve (AUC) of roflumilast, the
      AUC of roflumilast N-oxide and tPDE4i. Individual AUC values were estimated from
      population models. RESULTS: Roflumilast pharmacokinetics were modelled with a two
      compartment model with first-order absorption including a lag time. A one
      compartment model with zero-order absorption was used for roflumilast N-oxide.
      The final models displayed good descriptive and predictive performance with no
      appreciable systematic trends versus time, dose or study. Posterior predictive
      checks and robustness analysis showed that the models adequately described the
      pharmacokinetic parameters and the covariate effects on disposition. For
      roflumilast, the covariates of sex, smoking and race influenced clearance; and
      food influenced the absorption rate constant and lag time. For roflumilast N
      oxide, age, sex and smoking influenced clearance; age, sex and race influenced
      the fraction metabolized; bodyweight influenced the apparent volume of
      distribution; and food influenced the apparent duration of formation. The COPD
      covariate increased the central volume of distribution of roflumilast by 184% and
      reduced its clearance by 39%; it also reduced the estimated volume of
      distribution of roflumilast N-oxide by 21% and reduced its clearance by 7.9%.
      Compared with the reference population (male, non-smoking, White, healthy, 40
      year-old subjects), the relative geometric mean [95% CI] tPDE4i was higher in
      patients with COPD (12.6% [-6.6, 35.6]), women (19.3% [8.2, 31.6]), Black
      subjects (42.1% [16.4, 73.4]), Hispanic subjects (28.2% [4.1, 57.9]) and older
      subjects (e.g. 8.3% [-11.2, 32.2] in 60-year-olds), and was lower in smokers (
      19.1% [-34.0, -0.7]). Among all possible subgroups in this analysis, the subgroup
      with maximal tPDE4i comprised elderly, Black, female, non-smoking, COPD patients
      (tPDE4i 217% [95% CI 107, 437] compared with the value in the reference
      population). The probability of a patient with tPDE4i at the population geometric
      mean [95% CI] was 13.0% [7.5, 18.5] for developing diarrhoea, 6.0% [2.6, 9.4] for
      nausea and 5.1% [1.9, 8.6] for headache. CONCLUSIONS: Covariate effects have a
      limited impact on tPDE4i. There was a general association between tPDE4i and the
      occurrence of common AEs in patients with COPD.

PMID- 20690783
TI  - Pharmacokinetics of vandetanib in subjects with renal or hepatic impairment.
AB  - BACKGROUND AND OBJECTIVE: Vandetanib, an oncology drug being evaluated in phase
      III clinical trials, undergoes significant renal and hepatic excretion. The
      objective of these two studies was to investigate the single-dose
      pharmacokinetics of vandetanib in subjects with renal or hepatic impairment in
      comparison with healthy subjects. SUBJECTS AND METHODS: Two open-label, parallel
      group studies were conducted at a single centre in Germany. Subjects aged 18-75
      years with a body mass index of 18-32 kg/m2 were eligible. The renal impairment
      study recruited subjects with normal renal function and mild, moderate and severe
      renal impairment according to creatinine clearance calculated from a 24-hour
      urine collection pre-dose. The hepatic impairment study recruited subjects with
      normal hepatic function and mild, moderate and severe hepatic impairment
      according to the Child-Pugh classification. All subjects received a single 800 mg
      oral vandetanib dose. Blood samples for measurement of vandetanib, N
      desmethylvandetanib and vandetanib N-oxide were collected before and at various
      timepoints after vandetanib administration for up to 63 days. Pharmacokinetic
      parameters were determined using noncompartmental methods. RESULTS: Thirty-two
      subjects were recruited for the renal impairment study (ten with normal renal
      function and six, ten and six with mild, moderate and severe impairment,
      respectively). Thirty subjects were recruited for the hepatic impairment study
      (eight with normal hepatic function and eight, eight and six with mild, moderate
      and severe impairment, respectively). The area under the plasma concentration
      time curve from time zero to infinity (AUC(infinity)) values of free vandetanib
      increased by approximately 46%, 62% and 79% in subjects with mild, moderate and
      severe renal impairment, respectively. These increases were statistically
      significant, with the increase in the severe renal impairment group having the
      possibility of being double the value observed in subjects with normal renal
      function (geometric least squares [GLS] mean ratio [renal impairment : normal
      renal function] of 1.79; 90% CI 1.39, 2.31). Peak plasma concentrations of free
      vandetanib increased slightly by approximately 7%, 9% and 11% in subjects with
      mild, moderate and severe renal impairment, respectively. Total plasma clearance
      of free vandetanib decreased with all degrees of renal dysfunction. Hepatic
      impairment did not have a statistically significant effect on the AUC(infinity)
      of total vandetanib. Peak plasma concentrations of total vandetanib were reduced
      in subjects with all classifications of hepatic impairment compared with normal
      hepatic function, with a statistically significant effect in the severe hepatic
      impairment group (GLS mean ratio 0.71; 90% CI 0.53, 0.96). Increased exposure to
      both metabolites was seen in subjects with renal impairment. Exposure to N
      desmethylvandetanib was reduced in subjects with hepatic impairment, while
      exposure to vandetanib N-oxide was increased in subjects with severe hepatic
      impairment. Vandetanib was well tolerated and had a similar tolerability profile
      in subjects with renal or hepatic impairment compared with healthy subjects.
      CONCLUSION: Exposure to vandetanib was increased by about 46%, 62% and 79% in
      subjects with mild, moderate and severe renal impairment, respectively. A
      doubling in exposure could be ruled out in subjects with mild or moderate renal
      impairment but not for those with severe renal impairment. The possibility of
      dose reductions in patients with severe renal impairment will need to be assessed
      when the safety and tolerability profile is fully defined. Exposure to vandetanib
      was not altered in subjects with hepatic impairment, and no dose adjustment would
      be expected in patients with hepatic impairment.

PMID- 20690784
TI  - Risk assessment in extrapolation of pharmacokinetics from preclinical data to
      humans.
AB  - BACKGROUND: Prediction of pharmacokinetics in humans is essential for translating
      preclinical data to humans and planning safe and efficient clinical studies. The
      performance of various methods in extrapolation of preclinical pharmacokinetic
      data to humans is usually benchmarked by the fraction of predictions falling
      within a predefined interval that is centred on the value observed clinically.
      Recently, such an approach was used to compare physiologically based
      pharmacokinetic (PBPK) modelling and allometry in predicting the pharmacokinetics
      of a set of compounds in humans. Here, we present an analysis of the same
      dataset, focusing on predictions falling outside such a relatively narrow and
      centrally located interval. These are the main risk determinants in extrapolation
      of preclinical pharmacokinetic data to humans and should therefore be thoroughly
      understood in a risk mitigation approach to the design of early-phase human
      studies. METHODS: Values that had been previously predicted by allometry and by
      PBPK modelling in terms of the apparent total clearance after oral
      administration, apparent volume of distribution, area under the plasma
      concentration-time curve, maximum plasma drug concentration, time to reach the
      maximum plasma concentration and terminal elimination half-life in humans were
      used to generate a log-transformed dataset of predicted/observed ratios. The
      probabilities of mispredicting the values of these pharmacokinetic parameters
      using PBPK modelling and allometry were estimated by a bootstrap procedure on
      this set of ratios. RESULTS: Our results, albeit from a limited dataset,
      indicated that although PBPK modelling yielded higher fractions of satisfactory
      predictions than allometry, both methodologies were associated with a significant
      and occasionally high probability of obtaining mispredictions of pharmacokinetic
      parameters by factors of >2, >3 and >10. In line with recent proposals to extend
      the goals of early-phase human studies beyond safety and tolerability, and
      considering the need to mitigate risks in studies dealing with novel and highly
      potent drug candidates, we discuss these results in a pharmacological context.
      CONCLUSIONS: Concise recommendations are given regarding the use of allometric
      and PBPK extrapolation methodologies in the translation process. The results
      presented here should alert clinical investigators to the limitations inherent in
      all approaches to prediction of human pharmacokinetics from preclinical data. We
      propose an adaptive approach to the design of early-phase clinical studies,
      particularly when dealing with compounds that are characterized by novel and only
      partially understood pharmacological profiles.

PMID- 20690785
TI  - Effect of inadequate response to treatment in patients with depression.
AB  - OBJECTIVES: To assess the effects of inadequate response to antidepressant
      treatment on healthcare resource utilization and on work productivity in patients
      diagnosed as having major depressive disorder (MDD). STUDY DESIGN: This study
      used data from the 2006 US National Health and Wellness Survey, a cross-sectional
      survey of adults 18 years and older. METHODS: Patients who self-reported a
      confirmed diagnosis of depression and were currently taking antidepressant
      medication were included in the analyses. Adequacy of antidepressant treatment
      response was determined from responses to the mental health domain of the 8-Item
      Short Form Health Survey (SF-8). Logistic regression analyses adjusted for
      demographics, comorbidity, and component scores on the SF-8 were used to
      determine the associations between inadequacy of treatment response and health
      outcomes. RESULTS: Of 5988 patients who met the inclusion criteria for the study,
      30.9% were classified as antidepressant treatment responders, 31.2% were partial
      responders, and 37.9% were nonresponders. Partial response and nonresponse to
      treatment were associated with greater likelihood of emergency department
      utilization (odds ratios [ORs], 1.26 and 1.54, respectively; P <.01 for both) and
      hospitalization (OR, 1.23; P = .05 and OR, 1.39; P <.01, respectively).
      Similarly, partial response and nonresponse were associated with lower likelihood
      of current employment (OR, 0.83; P = .01 and OR, 0.63; P <.01, respectively) and
      with greater likelihood of work productivity loss among the employed (ORs, 1.42
      and 1.99, respectively; P <.01 for both). CONCLUSIONS: Patients with MDD who
      failed to respond to antidepressant treatment as evidenced by poor self-reported
      mental health status used more healthcare resources, were less likely to be
      employed, and had more work productivity loss than those who responded to
      antidepressant therapy.

PMID- 20690786
TI  - Anticonvulsant use after formulary status change for brand-name second-generation
      anticonvulsants.
AB  - BACKGROUND: Anticonvulsant medications are commonly used for off-label
      indications. However, managed care organizations can restrict utilization of
      medication to indicated uses only. OBJECTIVE: To evaluate the pattern of off
      label use of second-generation anticonvulsants after implementing a formulary
      change. METHODS: We did a retrospective analysis of an administrative pharmacy
      claims database for a managed care plan with more than 1 million members
      continuously enrolled during 2004-2005. The study evaluated off-label use and
      explored pharmacy utilization patterns (by physician specialty, region, plan
      type, age, sex, copayment) across the study population following the formulary
      change. RESULTS: A total of 10,185 patients had at least 1 pharmacy claim (total
      of 137,638 claims) for a second-generation anticonvulsant during the study
      period. Most members were female (68%), and 4.9% were <18 years old. A total of
      3986 of 4698 patients (84.8%) and 4600 of 5487 patients (83.8%) had
      anticonvulsants prescribed for off-label use in 2004 and 2005, respectively (P =
      .162). The off-label usage pattern varied for individual anticonvulsants in 2004
      and 2005 (P <.050), which may have been because of the change to nonpreferred
      coverage. Primary care physicians accounted for 41.3% of the prescribing of
      second-generation anticonvulsants for off-label uses, followed by neurologists
      (9.4%), psychiatrists (2.8%), and other (46.5%). The coverage change resulted in
      cost savings for the plan of $0.16 per member per month. CONCLUSIONS: The off
      label usage pattern varied for individual anticonvulsants in 2004 and 2005.
      Future considerations for controlling off-label use may include requiring prior
      authorization and provider education.

PMID- 20690787
TI  - Employees' willingness to pay to prevent influenza.
AB  - OBJECTIVES: To quantify employees' preferences, as measured by willingness to
      pay, to prevent influenza in themselves and in their child and adult household
      members and to examine factors associated with willingness to pay. STUDY DESIGN:
      Prospective observational cohort study of a convenience sample of employees from
      3 large US employers. Participants had at least 1 child (< or = 17 years) living
      in their household for at least 4 days per week. METHODS: Each month from
      November 2007 to April 2008, employees completed Web-based surveys regarding
      acute respiratory illness in their household. In the final survey, employees were
      presented with descriptions of influenza and questions regarding their
      willingness to pay to prevent influenza. Factors associated with willingness to
      pay were examined using multivariate ordinary least squares regression analysis
      of the log of willingness to pay. RESULTS: Among 2006 employees, 31.3% were
      female, the mean age was 41.7 years, 85.3% were of white race/ethnicity, and the
      mean household size was 4.0. Employees' median (mean) willingness to pay to
      prevent influenza was $25 ($72) for themselves, $25 ($82) for their adult
      household members, and $50 ($142) (P <.01) for children. However, influenza
      vaccination rates were approximately equal for children (27.5%), employees
      (31.5%), and other adult household members (24.5%). This finding may be explained
      by barriers such as cost, dislike of vaccinations, and disagreement with national
      influenza vaccination recommendations, which were significantly associated with
      lower willingness to pay for prevention of influenza (P <.05). CONCLUSION:
      Employees expressed a stronger preference to prevent influenza in their children
      than in themselves or other household members; however, modifiable barriers
      depress vaccination rates.

PMID- 20690788
TI  - Using search engine query data to track pharmaceutical utilization: a study of
      statins.
AB  - OBJECTIVE: To examine temporal and geographic associations between Google queries
      for health information and healthcare utilization benchmarks. STUDY DESIGN:
      Retrospective longitudinal study. METHODS: Using Google Trends and Google
      Insights for Search data, the search terms Lipitor (atorvastatin calcium; Pfizer,
      Ann Arbor, MI) and simvastatin were evaluated for change over time and for
      association with Lipitor revenues. The relationship between query data and
      community-based resource use per Medicare beneficiary was assessed for 35 US
      metropolitan areas. RESULTS: Google queries for Lipitor significantly decreased
      from January 2004 through June 2009 and queries for simvastatin significantly
      increased (P <.001 for both), particularly after Lipitor came off patent (P <.001
      for change in slope). The mean number of Google queries for Lipitor correlated (r
      = 0.98) with the percentage change in Lipitor global revenues from 2004 to 2008
      (P <.001). Query preference for Lipitor over simvastatin was positively
      associated (r = 0.40) with a community's use of Medicare services. For every 1%
      increase in utilization of Medicare services in a community, there was a 0.2-unit
      increase in the ratio of Lipitor queries to simvastatin queries in that community
      (P = .02). CONCLUSIONS: Specific search engine queries for medical information
      correlate with pharmaceutical revenue and with overall healthcare utilization in
      a community. This suggests that search query data can track community-wide
      characteristics in healthcare utilization and have the potential for informing
      payers and policy makers regarding trends in utilization.

PMID- 20690789
TI  - Mucoadhesive controlled release microcapsules of indomethacin: optimization and
      stability study.
AB  - The aim of this project was to develop and optimize indomethacin microcapsules
      composed of multiple mucoadhesive polymers for high drug entrapment, good
      mucoadhesiveness and drug release in a controlled fashion over a longer period of
      time. Microcapsules containing sodium alginate, sodium carboxymethylcellulose,
      methylcellulose, Carbopol 934 and hydroxypropyl methylcellulose were prepared by
      orifice-ionic gelation method. The effects of composition of microcapsules on
      drug entrapment efficacy, drug release and mucoadhesive character were determined
      by mixture statistical design. Most formulations exhibited good mucoadhesive
      property in everted intestinal sac test. Drug entrapment efficiency (68-94%) was
      dependent on the type of polymers. Drug release (92-100%) extended over 12 h. The
      optimized formulation resulted in drug entrapment efficiency of 89.3%, drug
      release of 94.8% and mucoadhesiveness of 30.4%. All formulations were stable for
      more than 1.5 years. The optimized mucoadhesive microcapsules are promising for
      controlled delivery of indomethacin with twice a day oral administration.

PMID- 20690790
TI  - Liposomes incorporating essential oil of Brazilian cherry (Eugenia uniflora L.):
      characterization of aqueous dispersions and lyophilized formulations.
AB  - Multilamellar liposomes incorporating essential oil of Brazilian cherry (Eugenia
      uniflora L.) leaves were produced by dry film hydration. Gas chromatography
      demonstrated the compounds found in the essential oil were effectively
      incorporated in the aqueous dispersions of liposomes. Differential scanning
      calorimetry analyses revealed the incorporation of the essential oil did not
      cause phase separation in the membrane structure; the gel-liquid crystalline
      transition temperature (main transition) remained the same despite the higher
      heterogeneity indicated by the transition peak broadening. Different
      cryoprotectors (sucrose and trehalose) were added to the liposomal formulations
      to be tested in their ability to protect the liposomal structure during the
      lyophilization. The morphological aspect of the lyophilized powders analysed by
      scanning electron microscopy showed significant differences among the samples
      with and without cryoprotectors. Fourier-transform infrared spectroscopy
      indicated the cryoprotectors interacted effectively with the polar heads of
      phospholipids in the bilayer. In terms of water absorption, trehalose was
      identified as a much more effective protector agent against it than sucrose. The
      cryoprotectors showed different degrees of effectiveness of preservation of the
      liposomal structure when the rehydration assays of lyophilized liposomes were
      carried out, as particle size measurements indicated a moderate process of fusion
      when the formulations with sucrose were rehydrated.

PMID- 20690791
TI  - Controlled release of bioactive recombinant human growth hormone from PLGA
      microparticles.
AB  - Controlled release formulation of recombinant human growth hormone (r-hGH) was
      achieved using poly lactide-co-glycolide (PLGA) polymer. Denaturation of r-hGH by
      dichloromethane during primary emulsification step of particle preparation was
      minimized by using human serum albumin whereas inclusion of sucrose and sodium
      bicarbonate helped in reducing protein denaturation during lyophilization and
      polymer particle degradation. Encapsulation efficiency of r-hGH entrapped in PLGA
      particles (size approximately 30 microm) was around 45% with protein load 20
      microg of r-hGH/mg of polymer particles. Porous particles showed quick release of
      r-hGH in comparison to non-porous particles in vitro. More than 10 ng/mL of
      bioactive r-hGH was found in the serum of the experimental animals observed for a
      30-day period after a single intramuscular injection of the polymeric
      formulation. Incorporation of optimal stabilizers is thus essential for the
      development of a stable, month long controlled release of polymer particle based
      r-hGH formulation.

PMID- 20690792
TI  - Evaluation of biocompatible stabilised gelled soya bean oil nanoparticles as new
      hydrophobic reservoirs.
AB  - Based on the organogel concept, in which an oil is trapped in a network of low
      molecular-mass organic gelator fibres creating a gel, a formulation of gelled
      soya bean oil nanoparticles was evaluated for its capacity to form biocompatible
      hydrophobic reservoirs. The aqueous dispersions of nanoparticles were prepared by
      hot emulsification (T degrees  > Tgel) and cooling at room temperature in the
      presence of polyethyleneimine (PEI). The dispersions were stabilised by the
      electrostatic interactions between the positively charged amino groups of the PEI
      and the negatively charged carboxylates of the gelator fibres present at the
      surface of the particles. The aqueous dispersions were highly stable (several
      months) and the gelled particles were able to entrap a hydrophobic fluorescent
      model molecule (Nile red), allowing testing in cells. The gelled oil
      nanoparticles were found to be biocompatible with the tested cells
      (keratinocytes) and had the ability to become rapidly internalised. Thus,
      organogel-based nanoparticles are a promising hydrophobic drug delivery system.

PMID- 20690793
TI  - Carbon nanotubes for transdermal drug delivery.
AB  - In this study, drug carrier properties through skin and penetration enhancement
      effects of carbon nanotubes (CNTs) are presented. Multi-walled and double-walled
      carbon nanotubes were used. Penetration enhancement into the skin following
      passive diffusion and iontophoresis were determined. Possible solubility
      enhancement effects and drug adsorption properties of CNTs were investigated.
      CNTs were found to be a useful drug carrier system and they can provide a high
      loading and enhanced transdermal penetration for especially hydrophobic drugs.
      The electroconductive nature of CNTs allows easy application of iontophoresis and
      the additional advantage of CNTs appears to be using them as electrodes.

PMID- 20690794
TI  - Enhanced therapeutic effect of LK-423 in treating experimentally induced colitis
      in rats when administered in colon delivery microcapsules.
AB  - LK-423 is a phthalimido-desmuramyl-dipeptide derivative with immunomodulating
      activity. In the present study the therapeutic efficacy of a colon-specific drug
      delivery system&#x2013;LK-423 microcapsules&#x2013;was examined in the 2,4,6
      trinitrobenzene sulphonic acid (TNBS)-induced ulcerative colitis model in rats.
      The colon-specific delivery of the drug using microcapsules relies on the
      combination of pH (outer gastroresistant coating), time (inner retard coating of
      Eudragit&#x00AE; RS and RL) and enzyme (pectin core) controlled drug release
      mechanisms. The optimal in vitro dissolution profile for LK-423 delivery to the
      colon of rats was obtained after coating newly developed LK-423 loaded pectin
      cores with 20% w/w of retard coating with a Eudragit&#x00AE; RS/RL ratio of
      8.5/1.5 and 30% w/w of enteric coating. Orally administered LK-423 microcapsules
      were therapeutically more beneficial in treating TNBS-induced ulcerative colitis
      in rats than orally or rectally administered LK-423 in the form of suspension.
      Clinical activity scores and colon weight to length ratio were insignificantly
      lower and the macroscopically estimated degree of healing was significantly
      greater. On the histological level, the administration of LK-423 microcapsules
      resulted in most physiological regeneration of intestinal mucosa, indicated by
      regular architecture of all mucosal tissue components, what is probably related
      to local drug delivery near the site of inflammation achieved using
      microcapsules. These results demonstrate that LK-23 colon delivery microcapsules
      enhance the therapeutic efficacy of the drug and therefore appear to be a useful
      approach for treating various inflammatory diseases in the large intestine.

PMID- 20690795
TI  - Restoration of fragile histidine triad (FHIT) expression inhibits cell growth and
      induces apoptosis in cutaneous T-cell lymphoma cell line.
AB  - To investigate the effects of fragile histidine triad (FHIT) restoration on cell
      proliferation and apoptosis in human cutaneous T-cell lymphoma cell line, Hut-78,
      in vitro and in nude mouse. Wild-type FHIT gene was transfected by liposome into
      the Hut-78 cells. The alteration of cell growth curve and soft agar colony
      formation was studied in vitro and in nude mice. The FHIT gene was stably
      expressed in Hut-78 cells after the transfection. Compared with the controls,
      restoration of FHIT expression inhibited cell growth and induced apoptosis. Tumor
      formation in vivo was strongly suppressed by FHIT gene restoration. Our data
      demonstrate restoration of FHIT gene expression inhibit the tumor cell growth and
      provide an option for the treatment.

PMID- 20690796
TI  - Localization and altered expression of nucleophosmin in the nuclear matrix during
      the differentiation of human hepatocarcinoma SMMC-7721 cells induced by HMBA.
AB  - Nucleophosmin (NPM1) is frequently upregulated and mutated in various tumor
      cells. To investigate the mechanism of induced differentiation of tumor cells,
      the nuclear matrix of human hepatocarcinoma SMMC-7721 cells induced by
      hexamethylene bisacetamide (HMBA) was selectively extracted and subjected to
      proteomic methodologies. We confirmed that NPM1 existed in nuclear matrix
      proteins and downregulated after HMBA treatment. By using immunogold
      electromicroscopy, we found that NPM1 was localized on nuclear matrix
      intermediate filaments. Our study also revealed the colocalization between NPM1
      and products of oncogenes or tumor suppressor genes including c-Fos, c-Myc, p53,
      and Rb by using laser scanning confocal microscopy in SMMC-7721 cells.

PMID- 20690797
TI  - Suppression of migration and invasion of PC3 prostate cancer cell line via
      activating E-cadherin expression by small activating RNA.
AB  - ABSTRACT Small activating RNAs are a recently discovered group of small,
      noncoding, and double-stranded RNA molecules that can induce sequence-specific
      transcriptional gene activation by targeting gene promoter regions. In the
      present study, we demonstrate that induction of E-cadherin expression by small
      activating RNA leads to suppression of migration and invasion of PC3 prostate
      cancer cells. The inhibitory effect was associated with relocalization of beta 
      catenin from the nucleus to the plasma membrane and decreased beta -catenin
      mediated transactivation. These data suggest that activation of E-cadherin by
      small activating RNA may have a therapeutic benefit for prostate and other types
      of cancer.

PMID- 20690798
TI  - Advantages of video questionnaire in estimating asthma prevalence and risk
      factors for school children: findings from an asthma survey in American Indian
      youth.
AB  - OBJECTIVES: The aims of the present study were to estimate the prevalence and
      risk factors of asthma among a sample of American Indian youth and to evaluate
      survey instruments used in determining asthma prevalence and risk factors.
      METHODS: Three hundred and fifty-two adolescents aged 9 to 21 years enrolled in
      an Indian boarding school completed an asthma screening. The survey instruments
      were a written questionnaire and a video-illustrated questionnaire prepared from
      the International Study of Asthma and Allergies in Childhood (ISAAC), school
      health records, and a health questionnaire. Participants also underwent
      spirometry testing. RESULTS: The prevalence of self-reported asthma varied from
      12.7% to 13.4% depending upon the instrument used and the questions asked. A
      history of hay fever, respiratory infections, and family history of asthma were
      found to be risk factors for asthma by all instruments. Female gender and living
      on a reservation were significantly associated with asthma by some, but not all,
      instruments. Airway obstruction was highly associated with one asthma symptom
      (wheeze) shown in the video questionnaire. Associations for most risk factors
      with asthma were strongest for the video questionnaire. CONCLUSIONS: The
      prevalence of self-reported asthma among these American Indian youth was similar
      to rates reported for other ethnic groups. The video-based questionnaire may be
      the most sensitive tool for identifying individuals at risk for asthma.

PMID- 20690799
TI  - Association of psychiatric disorders, asthma and lung function in early
      adulthood.
AB  - OBJECTIVE: To examine the association between psychiatric disorders, asthma, and
      lung function in young adults. STUDY DESIGN: Data were from the Mater-University
      of Queensland Study of Pregnancy (MUSP). The study was based on 2443 young adults
      (1193 male and 1250 female) for whom data were available on psychiatric
      disorders, asthma, and respiratory function. Life time and last 12 months'
      generalized anxiety, panic, posttraumatic stress disorder (PTSD), and depressive
      disorders were assessed using a computerised version of the Composite
      International Diagnostic Interview (CIDI-Auto). A Spirobank G spirometer system
      was used to measure forced vital capacity (FVC), forced expiratory volume in one
      second (FEV(1)), and forced expiratory flow between 25% and 75% of forced vital
      capacity (FEF(25-75%)). RESULTS: Participants with mental health disorders were
      more likely to have experienced asthma before or to use asthma medication at 21
      years. However, for both males and females, life time and last 12 months'
      experience of generalized anxiety, panic, PTSD, and depressive disorders were not
      statistically significantly associated with FVC, FEV(1), and FEF(25-75%), except
      a modest association with major depressive disorders for males. CONCLUSION: There
      is an association between mental health and asthma, but the relationship between
      mental health and lung function appeared to be confounded by the respondent's
      gender. More narrowly based prospective studies are required to determine the
      causal pathway between mental disorders and asthma.

PMID- 20690800
TI  - Manganese superoxide dismutase expression as a function of genotype and lung
      cancer pathology.
AB  - INTRODUCTION: The aim of this study was to compare the manganese superoxide
      dismutase (MnSOD) expression in matched tumor and normal tissue. METHODS: One
      hundred lung cancer specimens and matched normal lung parenchyma from the same
      patient were evaluated for MnSOD expression. RESULTS: The median normal MnSOD
      expression was 42% with a range of 10 to 70%, which was significantly greater (p
      = .001) than the median MnSOD expression in the tumor samples that was 18.8% and
      ranged from 1.1 to 50%. CONCLUSION: MnSOD expression is significantly reduced in
      lung adenocarcinoma and squamous cell carcinoma compared to the matched normal
      lung tissue.

PMID- 20690801
TI  - CRH and SRIF have opposite effects on the Wnt/beta-catenin signalling pathway
      through PKA/GSK-3beta in corticotroph pituitary cells.
AB  - The Wnt/beta-catenin signalling pathway is involved in tumorigenesis including
      endocrine tumors. We investigated the Wnt/beta-catenin pathway's modulation by
      corticotropin-releasing hormone (CRH) and somatostatin or somatotropin release
      inhibiting factor (SRIF) in mouse pituitary AtT-20 corticotroph cells. The
      Wnt/beta-catenin signalling pathway was activated by CRH and inhibited by SRIF.
      We provide evidence that cAMP/PKA signalling is involved affecting the GSK-3beta
      phosphorylation status at phospho-GSK-3beta (Ser9), thereby altering beta-catenin
      degradation downstream. Furthermore, CRH and SRIF showed concordant effects on
      cell proliferation. Our data demonstrate an important role of the Wnt/beta
      catenin pathway in the proliferative control of pituitary corticotroph cells and
      describe a mechanism for its regulation by CRH and SRIF.

PMID- 20690802
TI  - A phase II trial of oxaliplatin and trastuzumab in the treatment of HER2-positive
      metastatic breast cancer.
AB  - We investigated the feasibility/efficacy of oxaliplatin in combination with
      trastuzumab as first-/second-line treatment of HER2-positive metastatic breast
      cancer (MBC). Patients received oxaliplatin/trastuzumab every 21 days and were
      evaluated every 6 weeks using RECIST criteria. The study closed early due to slow
      accrual. Twenty-five patients were evaluable; of these, 5 (20%) had objective
      responses to oxaliplatin/trastuzumab. Therapy was well tolerated (no grade-4 and
      gastrointestinal grade-3 toxicity in 4% of patients), but had only modest
      activity (median time-to-progression 1.8 months). Substitution of oxaliplatin for
      cisplatin or carboplatin, in combination with trastuzumab, does not appear to
      improve first-/second-line therapy in HER2-positive MBC.

PMID- 20690803
TI  - Implications of mutational analysis for the management of patients with
      gastrointestinal stromal tumors and the application of targeted therapies.
AB  - The receptor tyrosine kinase inhibitors, imatinib and sunitinib, have
      significantly improved the prognosis for patients with advanced gastrointestinal
      stromal tumors (GISTs). Most GISTs exhibit mutations in the genes encoding the
      stem cell factor receptor (KIT) or platelet-derived growth factor receptor alpha
      (PDGFRA). Imatinib is more effective in patients with KIT exon 11 mutations
      compared with KIT exon 9 mutations and wild-type genotype, while sunitinib
      confers greater in vitro efficacy in patients with KIT exon 9 mutants and wild
      type genotype than in KIT exon 11 mutants. This review examines the potential
      role of mutational analysis to optimize therapy with imatinib and sunitinib for
      GIST.

PMID- 20690804
TI  - A lower Allred score for progesterone receptor is strongly associated with a
      higher recurrence score of 21-gene assay in breast cancer.
AB  - Among the 77 infiltrating breast carcinomas, we found that progesterone receptor
      (PR) expression was inversely associated with recurrence score (RS, p < .0001).
      RS is also significantly associated with tubule formation, mitosis, and luminal B
      subtype. The equation of RS = 17.489 + 2.071 (tubal formation) + 2.926 (mitosis) 
      2.408 (PR) -1.061 (HER2) + 7.051 (luminal A) + 29.172 (luminal B) predicts RS
      with an R2 of 0.65. In conclusion, PR negativity, luminal B subtype, tubal
      formation, and mitosis are strongly correlated with a higher RS.

PMID- 20690806
TI  - A phase II trial of vinflunine as monotherapy or in combination with trastuzumab
      as first-line treatment of metastatic breast cancer.
AB  - We investigated the microtubulin inhibitor vinflunine-with trastuzumab in human
      epidermal growth factor receptor-2 (HER2)-positive patients-as first-line
      metastatic breast cancer therapy. HER2-negative patients received vinflunine on
      day 1; HER2-positive patients received vinflunine/trastuzumab every 21 days.
      Forty-eight patients in each treatment group were planned; the sponsor terminated
      the study early. Thirty-two evaluable patients (vinflunine, 11;
      vinflunine/trastuzumab, 21) were enrolled. In HER2-positive patients,
      vinflunine/trastuzumab produced an objective response rate (33%), clinical
      benefit rate (71%), and progression-free survival (6.2 months). Grade-3/4
      neutropenia occurred in 14 (44%) patients; gastrointestinal toxicities were
      common and six patients were hospitalized for treatment-related toxicity. The
      vinflunine/trastuzumab combination was active and well tolerated, but our results
      do not suggest advantages over taxane/trastuzumab or vinorelbine/trastuzumab.

PMID- 20690805
TI  - The endothelin axis stimulates the expression of pro-inflammatory cytokines and
      pro-migratory molecules in breast cancer.
AB  - We investigated the effects of the endothelin-1 (ET-1) receptor dual antagonist
      (Bosentan(r)) on the inflammatory cytokines and the chemoattractant molecules
      associated with breast cancer growth and the development of tumor infiltration in
      bone explants. Immunocompetent mice implanted with the murine mammary carcinoma
      4T1 cells in a skin-fold chamber and treated with Bosentan(r) had reduced tumor
      growth (p < .05). ET-1 promoted the secretion of the anti-inflammatory soluble
      tumor necrosis factor (TNF) receptor and IL12 p40 in vitro. The Bosentan(r)
      treatment in vivo was associated with a local increase of the anti-inflammatory
      IL-1alpha cytokine concentration and decrease of the pro-inflammatory TNF-alpha
      and IL-17 cytokine concentrations (p < .05).

PMID- 20690807
TI  - Population-based estimate of the prevalence of HER-2 positive breast cancer
      tumors for early stage patients in the US.
AB  - The goal of this study was to estimate prevalence of HER-2 positive tumors in a
      population-based sample of 1026 women diagnosed in 2005 with early stage breast
      cancer. We modeled the relationship between patient and tumor characteristics and
      HER-2. HER-2 positive estimates were 19% for women aged <= 49 years and 15% aged
      >= 50 years. HER-2 varied by tumor grade and size in women aged <= 49 years but
      was not significant in multivariate analysis. Tumor grade and race were
      associated with HER-2 for women aged >= 50 years after controlling for other
      variables. HER-2 varies by age and by race and tumor in older women.

PMID- 20690808
TI  - Berrettini branch.

PMID- 20690809
TI  - Neurosurgical treatment of cancer pain.

PMID- 20690810
TI  - Destructive procedures for control of cancer pain: the case for cordotomy.
AB  - OBJECT: Historically, destructive procedures for cancer pain were the main line
      of treatment therapy. However, the use of high-dose opioids has essentially
      replaced such procedures. Recognition of the limits of medical therapy to treat
      cancer pain effectively is growing, while conversely, in regions with limited
      access to pain medications, the importance of destructive surgical techniques is
      increasing. A critical evaluation of the evidence for destructive techniques is
      warranted, and the authors review current evidence underlying these procedures.
      METHODS: A US National Library of Medicine PubMed search for "ablation," "DREZ,"
      "dorsal root entry zone," "cingulotomy," "cordotomy," "ganglionectomy,"
      "mesencephalotomy," "myelotomy," "neurotomy," "neurectomy," "rhizotomy,"
      "sympathectomy," "thalamotomy," "tractotomy," and "pain" was undertaken. The
      search was then limited to human studies, English-language literature, cancer
      pain, and reports with more than 1 patient. RESULTS: One hundred twenty papers
      were identified and reviewed based on the selection criteria described. According
      to the Canadian and US task forces, classification of clinical research
      literature only "sympathectomy" was supported by Class I or II studies, with 2
      Class I papers and 1 Class II paper identified for cancer pain. All other
      procedures were supported by Class III studies of variable quality. Cordotomy in
      particular was the most extensively studied and reviewed procedure. Given the
      large number of patients studied, consistent results, multiplicity of reports
      and, even though evidence quality for individual studies was relatively low,
      cumulative evidence suggests that cordotomy may play an important role in the
      treatment of cancer pain. CONCLUSIONS: Destructive procedures for cancer pain may
      play more than a historic role in the management of cancer pain. Cumulative
      evidence from even the poorest quality studies suggests that some procedures,
      such as cordotomy, should be included in the armamentarium available to the
      neurosurgeon today. To renew appropriate interest in these procedures, evidence
      and studies that meets today's evidence-based research criteria are warranted.

PMID- 20690811
TI  - Letter to the editor. Intraconal lesions.

PMID- 20690812
TI  - Multiple craniotomies.

PMID- 20690813
TI  - Multiple craniotomies in the management of multifocal and multicentric
      glioblastoma. Clinical article.
AB  - OBJECT: Multiple craniotomies have been performed for resection of multiple brain
      metastases in the same surgical session with satisfactory outcomes, but the role
      of this procedure in the management of multifocal and multicentric glioblastomas
      is undetermined, although it is not the standard approach at most centers.
      METHODS: The authors performed a retrospective analysis of data prospectively
      collected between 1993 and 2008 in 20 patients with multifocal or multicentric
      glioblastomas (Group A) who underwent resection of all lesions via multiple
      craniotomies during a single surgical session. Twenty patients who underwent
      resection of solitary glioblastoma (Group B) were selected to match Group A with
      respect to the preoperative Karnofsky Performance Scale (KPS) score, tumor
      functional grade, extent of resection, age at time of surgery, and year of
      surgery. Clinical and neurosurgical outcomes were evaluated. RESULTS: In Group A,
      the median age was 52 years (range 32-78 years); 70% of patients were male; the
      median preoperative KPS score was 80 (range 50-100); and 9 patients had
      multicentric glioblastomas and 11 had multifocal glioblastomas. Aggressive
      resection of all lesions in Group A was achieved via multiple craniotomies in the
      same session, with a median extent of resection of 100%. Groups A and B were
      comparable with respect to all the matching variables as well as the amount of
      tumor necrosis, number of cysts, and the use of intraoperative navigation. The
      overall median survival duration was 9.7 months in Group A and 10.5 months in
      Group B (p = 0.34). Group A and Group B (single craniotomy) had complication
      rates of 30% and 35% and 30-day mortality rates of 5% (1 patient) and 0%,
      respectively. CONCLUSIONS: Aggressive resection of all lesions in selected
      patients with multifocal or multicentric glioblastomas resulted in a survival
      duration comparable with that of patients undergoing surgery for a single lesion,
      without an associated increase in postoperative morbidity. This finding may
      indicate that conventional wisdom of a minimal role for surgical treatment in
      glioblastoma should at least be questioned.

PMID- 20690814
TI  - An observational study to assess changes in arterial blood gas values during
      untreated porcine ventricular fibrillation.
AB  - BACKGROUND: Cardiocerebral resuscitation (CCR) is reportedly superior to
      cardiopulmonary resuscitation (CPR) for out-of-hospital cardiac arrest (OHCA)
      even though active ventilation is not initially provided. Understandably,
      concerns have been raised regarding the withholding of positive pressure
      ventilation (PPV) during CCR because of the longstanding belief that respiratory
      gas exchange is a critical action during resuscitation. OBJECTIVE: In this
      observational study, we sought to quantify the effect of prolonged untreated
      ventricular fibrillation (VF) on arterial pH, partial pressure of carbon dioxide
      (pCO(2)), and partial pressure of oxygen (pO(2)) values in a swine model of
      witnessed cardiac arrest to begin exploring the validity of these concerns.
      METHODS: Both included studies were approved by the institutional animal care and
      use committee (IACUC). Eighty-three animals (25-35 kg) were instrumented under
      general anesthesia. Baseline characteristics were recorded. An arterial blood gas
      (ABG) sample was drawn from each animal via femoral catheter just prior to
      electrical induction of VF. After 8 minutes of untreated VF in one study (study 1
      [n = 30]) and 10 minutes of untreated VF in the other study (study 2 [n = 53]), a
      second ABG sample was drawn. All samples were processed immediately using an i
      STAT portable whole blood analyzer. Baseline characteristics of animals in the
      two studies were assessed using descriptive statistics. For the second ABG sample
      in each study, the mean pH, pCO(2), and pO(2) values, with 95% confidence
      intervals (95% CIs), were determined. The paired ABG results for each animal were
      then compared and the average pH, pCO(2), and pO(2) proportions, with 95% CIs,
      for each study were calculated. RESULTS: The baseline characteristics of the
      animals in the two studies were similar. After 8 and 10 minutes of untreated VF
      cardiac arrest, the pH values were 7.35 (95% CI = 7.32, 7.37) and 7.37 (95% CI =
      7.36, 7.38), the pCO(2) increased to 44.1 mmHg (95% CI = 41.1, 47.1) and 52.7
      mmHg (95% CI = 51.0, 54.4), and the pO(2) decreased to 44.8 mmHg (95% CI = 42.2,
      47.4) and 45.5 mmHg (95% CI = 43.3, 47.6), respectively. CONCLUSIONS: Using our
      swine model of witnessed cardiac arrest with prolonged untreated VF, the arterial
      pH remained essentially unchanged and the pCO(2) increased to 1.42 times baseline
      after 10 minutes, while almost half of the initial O(2) concentration in the
      blood at the beginning of resuscitation remained.

PMID- 20690815
TI  - Consumers' views of direct-to-consumer genetic information.
AB  - In this report, we describe the evolution and types of genetic information
      provided directly to consumers, discuss potential advantages and disadvantages of
      these products, and review research evaluating consumer responses to direct-to
      consumer (DTC) genetic testing. The available evidence to date has focused on
      predictive tests and does not suggest that individuals, health care providers, or
      health care systems have been harmed by a DTC provision of genetic information.
      An understanding of consumer responses to susceptibility tests has lagged behind.
      The Multiplex Initiative is presented as a case study of research to understand
      consumers' responses to DTC susceptibility tests. Three priority areas are
      recommended for accelerated research activities to inform public policy regarding
      DTC genetic information: (a) exploring consumer's long-term responses to DTC
      genetic testing on a comprehensive set of outcomes, (b) evaluating optimal
      services to support decision making about genetic testing, and (c) evaluating
      best practices in promoting genetic competencies among health providers.

PMID- 20690816
TI  - Public attitudes and beliefs about genetics.
AB  - The existing research base on public attitudes about genetics shows that people's
      attitudes vary according to the specific technologies and purposes to which
      genetic knowledge is applied. Genetic testing is viewed highly favorably,
      genetically modified food is viewed with ambivalence, and cloning is viewed
      negatively. Attitudes are favorable for uses that maintain a perceived natural
      order and unfavorable for uses that are perceived to change it. Public concerns
      about control of genetic information and eugenics are evident, but their strength
      and relevance to policy preference are unclear. The pattern of attitudes can be
      explained by theories of attitude formation, and the existing base of information
      can be deepened and given more explanatory and predictive power by integrating
      future research into the various traditions that theorize attitude formation.

PMID- 20690817
TI  - Contrasting methods of quantifying fine structure of human recombination.
AB  - There has been considerable excitement over the ability to construct linkage maps
      based only on genome-wide genotype data for single nucleotide polymorphic sites
      (SNPs) in a population sample. These maps, which are derived from estimates of
      linkage disequilibrium (LD), rely on population genetics theory to relate the
      decay of LD to the local rate of recombination, but other population processes
      also come into play. Here we contrast these LD maps to the classically derived,
      pedigree-based human recombination maps. The LD maps have a level of resolution
      greatly exceeding that of the pedigree maps, and at this fine scale, sperm typing
      allows a means of validation. While at a gross level both the pedigree maps and
      the sperm typing methods generally agree with LD maps, there are significant
      local differences between them, and the fact that these maps measure different
      genetic features should be remembered when using them for other genetic
      inferences.

PMID- 20690818
TI  - The mitochondrial proteome and human disease.
AB  - For nearly three decades, the sequence of the human mitochondrial genome (mtDNA)
      has provided a molecular framework for understanding maternally inherited
      diseases. However, the vast majority of human mitochondrial disorders are caused
      by nuclear genome defects, which is not surprising since the mtDNA encodes only
      13 proteins. Advances in genomics, mass spectrometry, and computation have only
      recently made it possible to systematically identify the complement of over 1,000
      proteins that comprise the mammalian mitochondrial proteome. Here, we review
      recent progress in characterizing the mitochondrial proteome and highlight
      insights into its complexity, tissue heterogeneity, evolutionary origins, and
      biochemical versatility. We then discuss how this proteome is being used to
      discover the genetic basis of respiratory chain disorders as well as to expand
      our definition of mitochondrial disease. Finally, we explore future prospects and
      challenges for using the mitochondrial proteome as a foundation for systems
      analysis of the organelle.

PMID- 20690819
TI  - Signaling pathways in human skeletal dysplasias.
AB  - Human skeletal dysplasias are disorders that result from errors in bone,
      cartilage, and joint development. A complex series of signaling pathways,
      including the FGF, TGFbeta, BMP, WNT, Notch, and Hedgehog pathways, are essential
      for proper skeletogenesis, and human skeletal dysplasias are often a consequence
      of primary or secondary dysregulation of these pathways. Although these pathways
      interact to regulate bone, cartilage, and joint formation, human genetic
      phenotypes point to the predominant action of specific components of these
      pathways. Mutations in the genes with a role in metabolic processing within the
      cell, the extracellular matrix, and transcriptional regulation can lead to
      dysregulation of cell-cell and cell-matrix signaling that alters tissue
      patterning, cell differentiation, proliferation, and apoptosis. We propose a
      morphogen rheostat model to conceptualize how mutations in different metabolic
      processes can lead to the integration of differential signaling inputs within a
      temporal and spatial context to generate apparently divergent skeletal
      phenotypes.

PMID- 20690820
TI  - Assembly of fibronectin extracellular matrix.
AB  - In the process of matrix assembly, multivalent extracellular matrix (ECM)
      proteins are induced to self-associate and to interact with other ECM proteins to
      form fibrillar networks. Matrix assembly is usually initiated by ECM
      glycoproteins binding to cell surface receptors, such as fibronectin (FN) dimers
      binding to alpha5beta1 integrin. Receptor binding stimulates FN self-association
      mediated by the N-terminal assembly domain and organizes the actin cytoskeleton
      to promote cell contractility. FN conformational changes expose additional
      binding sites that participate in fibril formation and in conversion of fibrils
      into a stabilized, insoluble form. Once assembled, the FN matrix impacts tissue
      organization by contributing to the assembly of other ECM proteins. Here, we
      describe the major steps, molecular interactions, and cellular mechanisms
      involved in assembling FN dimers into fibrillar matrix while highlighting
      important issues and major questions that require further investigation.

PMID- 20690821
TI  - Role of tissue factor in venous thrombosis.
AB  - Venous thromboembolism (VTE) is a leading cause of morbidity and mortality
      worldwide. However, the mechanisms by which clots are formed in the deep veins
      have not been determined. Tissue factor (TF) is the primary initiator of the
      coagulation cascade and is essential for hemostasis. Under pathological
      conditions, TF is released into the circulation on small-membrane vesicles termed
      microparticles (MPs). Recent studies suggest that elevated levels of MP TF may
      trigger thrombosis. This review provides an overview of the role of TF in VTE.

PMID- 20690822
TI  - A long affair with renal tubules.
AB  - This essay provides a summary of my professional activities. My interest in renal
      physiology started as a medical student in Vienna, when I became acquainted with
      Homer Smith's essays on kidney function. After moving to the United States in
      1951, I was fortunate to be mentored by Robert Pitts, in whose Department of
      Physiology at Cornell Medical College in New York I was given early independence,
      intellectual stimulation, and the opportunity to pursue experiments on single
      renal tubules. The problem of how the nephron manages its myriad of transport
      functions has never lost its fascination for me, and I am profoundly grateful to
      the many colleagues at Cornell Medical College and at Yale University School of
      Medicine who shared my passion for the kidney.

PMID- 20690823
TI  - Genomes in conflict: maintaining genome integrity during virus infection.
AB  - The cellular surveillance network for sensing and repairing damaged DNA prevents
      an array of human diseases, and when compromised it can lead to genomic
      instability and cancer. The carefully maintained cellular response to DNA damage
      is challenged during viral infection, when foreign DNA is introduced into the
      cell. The battle between virus and host generates a genomic conflict. The host
      attempts to limit viral infection and protect its genome, while the virus deploys
      tactics to eliminate, evade, or exploit aspects of the cellular defense. Studying
      this conflict has revealed that the cellular DNA damage response machinery
      comprises part of the intrinsic cellular defense against viral infection. In this
      review we examine recent advances in this emerging field. We identify common
      themes used by viruses in their attempts to commandeer or circumvent the host
      cell's DNA repair machinery, and highlight potential outcomes of the conflict for
      both virus and host.

PMID- 20690824
TI  - Signaling mechanisms of HAMP domains in chemoreceptors and sensor kinases.
AB  - HAMP domains mediate input-output signaling in histidine kinases, adenylyl
      cyclases, methyl-accepting chemotaxis proteins, and some phosphatases. HAMP
      subunits have two 16-residue amphiphilic helices (AS1, AS2) joined by a 14- to 15
      residue connector segment. Two alternative HAMP structures in these homodimeric
      signaling proteins have been described: HAMP(A), a tightly packed, parallel, four
      helix bundle; and HAMP(B), a more loosely packed bundle with an altered AS2/AS2'
      packing arrangement. Stimulus-induced conformational changes probably modulate
      HAMP signaling by shifting the relative stabilities of these opposing structural
      states. Changes in AS2/AS2' packing, in turn, modulate output signals by altering
      structural interactions between output helices through heptad repeat stutters
      that produce packing phase clashes. Output helices that are too tightly or too
      loosely packed most likely produce kinase-off output states, whereas kinase-on
      states require an intermediate range of HAMP stabilities and dynamic behaviors. A
      three-state, dynamic bundle signaling model best accounts for the signaling
      properties of chemoreceptor mutants and may apply to other transducers as well.

PMID- 20690825
TI  - DNA viruses: the really big ones (giruses).
AB  - Viruses with genomes greater than 300 kb and up to 1200 kb are being discovered
      with increasing frequency. These large viruses (often called giruses) can encode
      up to 900 proteins and also many tRNAs. Consequently, these viruses have more
      protein-encoding genes than many bacteria, and the concept of small
      particle/small genome that once defined viruses is no longer valid. Giruses
      infect bacteria and animals although most of the recently discovered ones infect
      protists. Thus, genome gigantism is not restricted to a specific host or
      phylogenetic clade. To date, most of the giruses are associated with aqueous
      environments. Many of these large viruses (phycodnaviruses and Mimiviruses)
      probably have a common evolutionary ancestor with the poxviruses, iridoviruses,
      asfarviruses, ascoviruses, and a recently discovered Marseillevirus. One issue
      that is perhaps not appreciated by the microbiology community is that large
      viruses, even ones classified in the same family, can differ significantly in
      morphology, lifestyle, and genome structure. This review focuses on some of these
      differences than on extensive details about individual viruses.

PMID- 20690826
TI  - Kawasaki disease: novel insights into etiology and genetic susceptibility.
AB  - Kawasaki disease (KD) is a vasculitis of young childhood that particularly
      affects the coronary arteries. Molecular analysis of the oligoclonal IgA response
      in acute KD led to production of synthetic KD antibodies. These antibodies
      identify intracytoplasmic inclusion bodies in acute KD tissues. Light and
      electron microscopic studies indicate that the inclusion bodies are consistent
      with aggregates of viral proteins and RNA. Advances in molecular genetic analysis
      and completion of the Human Genome Project have sparked a worldwide effort to
      identify genes associated with KD. A polymorphism of one such gene, ITPKC, a
      negative regulator of T cell activation, confers susceptibility to KD in Japanese
      populations and increases the risk of developing coronary artery abnormalities in
      both Japanese and U.S. children. Identification of the etiologic agent and of
      genes conferring KD susceptibility are the best means of improving diagnosis and
      therapy and enabling prevention of this important disorder of childhood.

PMID- 20690827
TI  - Cognitive therapy: current status and future directions.
AB  - Cognitive therapy is a system of psychotherapy with a powerful theoretical
      infrastructure, which has received extensive empirical support, and a large body
      of research attesting to its efficacy for a wide range of psychiatric and medical
      problems. This article provides a brief overview of the conceptual and practical
      components of cognitive therapy and highlights some of the empirical evidence
      regarding its efficacy. Cognitive therapy (often labeled generically as cognitive
      behavior therapy) is efficacious either alone or as an adjunct to medication and
      provides a prophylaxis against relapse and recurrence.

PMID- 20690828
TI  - Energetics of insect diapause.
AB  - Managing metabolic resources is critical for insects during diapause when food
      sources are limited or unavailable. Insects accumulate reserves prior to
      diapause, and metabolic depression during diapause promotes reserve conservation.
      Sufficient reserves must be sequestered to both survive the diapause period and
      enable postdiapause development that may involve metabolically expensive
      functions such as metamorphosis or long-distance flight. Nutrient utilization
      during diapause is a dynamic process, and insects appear capable of sensing their
      energy reserves and using this information to regulate whether to enter diapause
      and how long to remain in diapause. Overwintering insects on a tight energy
      budget are likely to be especially vulnerable to increased temperatures
      associated with climate change. Molecular mechanisms involved in diapause
      nutrient regulation remain poorly known, but insulin signaling is likely a major
      player. We also discuss other possible candidates for diapause-associated
      nutrient regulation including adipokinetic hormone, neuropeptide F, the cGMP
      kinase For, and AMPK.

PMID- 20690829
TI  - Bemisia tabaci: a statement of species status.
AB  - Bemisia tabaci has long been considered a complex species. It rose to global
      prominence in the 1980s owing to the global invasion by the commonly named B
      biotype. Since then, the concomitant eruption of a group of plant viruses known
      as begomoviruses has created considerable management problems in many countries.
      However, an enduring set of questions remains: Is B. tabaci a complex species or
      a species complex, what are Bemisia biotypes, and how did all the genetic
      variability arise? This review considers these issues and concludes that there is
      now sufficient evidence to state that B. tabaci is not made up of biotypes and
      that the use of biotype in this context is erroneous and misleading. Instead, B.
      tabaci is a complex of 11 well-defined high-level groups containing at least 24
      morphologically indistinguishable species.

PMID- 20690830
TI  - Alcohol-associated illness and injury and ambulance calls in a midwestern college
      town: a four-year retrospective analysis.
AB  - BACKGROUND: Alcohol is often a factor in illness and injury among college-aged
      individuals. Ambulance services responding to 9-1-1 calls in college towns
      regularly encounter patients who have consumed alcohol to the point of
      intoxication and subsequently suffered an injury or experienced an illness
      necessitating prehospital emergency care. OBJECTIVES: The first objective was to
      review ambulance calls in a Midwestern college town in order to identify patterns
      or trends related to alcohol consumption. Another objective was to determine to
      what extent, if any, underage drinking was a factor in these calls. A final
      objective was to determine whether there were types of illness or injuries
      related to 9-1-1 calls that were involved with alcohol consumption among college
      aged students. METHODS: This was a retrospective study using secondary data of
      four years of ambulance calls that occurred in a specific geographic region of a
      college town. All patient care reports (PCRs) included alcohol consumption as a
      pertinent factor in the call. Data were de-identified and in some cases
      aggregated to ensure confidentiality. Descriptive statistics were used to
      identify prevalence and incidence of injury and illness and patient demographics.
      RESULTS: Of the ambulance calls for service in the geographic area, 44.4% to
      45.8% identified as "downtown" had alcohol consumption as a reported factor in
      the PCR. The number of calls for service that involved patients below the legal
      drinking age (21 years) was small but increased between 2004 and 2007. Calls
      involving male patients made up the majority of calls with alcohol as a factor.
      The majority of alcohol-related calls for service were for traumatic injuries,
      sexual assaults and rapes, poisonings or drug ingestions, and altered levels of
      consciousness. CONCLUSION: Alcohol consumption was a comorbid factor in illness
      and injury that necessitated prehospital emergency medical care in one Midwestern
      college town. Further research is needed to determine whether these results can
      be generalized beyond this one geographic location or if causality can be
      determined between alcohol consumption and injuries or illnesses that lead to
      emergency medical services calls.

PMID- 20690831
TI  - Immediate implantation with ridge augmentation using acellular dermal matrix and
      deproteinized bovine bone: a case report.
AB  - Immediate implant placement combined with hard and soft tissue grafting has been
      suggested because it may preclude dramatic postextraction bone loss and may
      decrease overall discomfort with reduction in the number of surgeries and in
      treatment time. In this case report, the acellular dermal matrix was used as a
      membrane for immediate implantation via a bone augmentation procedure in an
      esthetically challenging situation. The author suggests that this surgical
      technique provides the clinician with an option for an immediate implant therapy
      when primary closure is not intended. Additional randomized controlled trials
      conducted over long periods are necessary to establish whether this procedure
      offers long-term benefit to patients.

PMID- 20690832
TI  - Relationship between smoking and bleeding on probing.
AB  - The objective of this study was to assess and compare bone loss (BL) around the
      dental implant platform as well as the presence of bacterial plaque (PBP),
      bleeding on probing (BOP), and periodontal probing depths (PD) of teeth and
      dental implants of smokers and nonsmokers. Three hundred forty-seven teeth and 98
      implants of 20 randomly selected patients were assessed (12 smokers and 8
      nonsmokers). The specimens were divided into 4 groups according to the site
      probed. Group 1 included smoker implant sites, group 2 included smoker tooth
      sites, group 3 included nonsmoker implant sites, and group 4 included nonsmoker
      tooth sites. The presence/absence of visible bacterial plaque, presence/absence
      of BOP, PD <= 3 mm or >3 mm, and BL around the dental implant platform were the
      data assessed. The PBP and BL showed statistical significance between smokers and
      nonsmokers. Bleeding on probing and PD <= 3 mm showed statistical significance
      between groups 1, 3, and 4. Comparing sites with BOP and PD > 3 mm, there was no
      statistical significance except for group 1, which did not present sites with
      these characteristics. Comparing sites with BOP and PD <= 3 mm, there was
      statistical significance between group 2 and groups 3 and 4. When comparing the
      prevalence of sites without BOP and PD > 3 mm, there was statistical significance
      between groups 1, 3, and 4. Smoking promotes a greater BL around the dental
      implant platform and results in vasoconstriction of the peri-implant and
      periodontal tissues.

PMID- 20690833
TI  - Medical diplomacy.

PMID- 20690835
TI  - Teleservices improve access to PTSD treatment.

PMID- 20690836
TI  - Healthcare delivery for oil rig workers: telemedicine plays a vital role.

PMID- 20690837
TI  - Determining accessibility to dermatologists and teledermatology locations in
      Kentucky: demonstration of an innovative geographic information systems approach.
AB  - Teledermatology provides a partial solution to the problem of accessibility to
      dermatology services in underserved areas, yet methodologies to determine the
      locations and geographic dimensions of these areas and the locational efficiency
      of remote teledermatology sites have been found wanting. This article illustrates
      an innovative Geographic Information Systems approach using dermatologists'
      addresses, U.S. Census population data, and the Topologically Integrated
      Geographic Encoding and Referencing System. Travel-time-based service areas were
      calculated and mapped for each dermatologist in the state of Kentucky and for
      possible locations of several remote teledermatology sites. Populations within
      the current and possible remote service areas were determined. These populations
      and associated maps permit assessment of the locational efficiency of the current
      distribution of dermatologists, location of underserved areas, and the potential
      contribution of proposed hypothetical teledermatology sites. This approach is a
      valuable and practical tool for evaluating access to current distributions of
      dermatologists as well as planning for and implementing teledermatology.

PMID- 20690839
TI  - Spectral region optimization for Raman-based optical biopsy of inflammatory
      lesions.
AB  - OBJECTIVE: The biochemical alterations between inflammatory fibrous hyperplasia
      (IFH) and normal tissues of buccal mucosa were probed by using the FT-Raman
      spectroscopy technique. The aim was to find the minimal set of Raman bands that
      would furnish the best discrimination. BACKGROUND: Raman-based optical biopsy is
      a widely recognized potential technique for noninvasive real-time diagnosis.
      However, few studies had been devoted to the discrimination of very common subtle
      or early pathologic states as inflammatory processes that are always present on,
      for example, cancer lesion borders. METHODS: Seventy spectra of IFH from 14
      patients were compared with 30 spectra of normal tissues from six patients. The
      statistical analysis was performed with principal components analysis and soft
      independent modeling class analogy cross-validated, leave-one-out methods.
      RESULTS: Bands close to 574, 1,100, 1,250 to 1,350, and 1,500 cm(-1) (mainly
      amino acids and collagen bands) showed the main intragroup variations that are
      due to the acanthosis process in the IFH epithelium. The 1,200 (C-C
      aromatic/DNA), 1,350 (CH(2) bending/collagen 1), and 1,730 cm(-1) (collagen III)
      regions presented the main intergroup variations. This finding was interpreted as
      originating in an extracellular matrix-degeneration process occurring in the
      inflammatory tissues. The statistical analysis results indicated that the best
      discrimination capability (sensitivity of 95% and specificity of 100%) was found
      by using the 530-580 cm(-1) spectral region. CONCLUSIONS: The existence of this
      narrow spectral window enabling normal and inflammatory diagnosis also had useful
      implications for an in vivo dispersive Raman setup for clinical applications.

PMID- 20690840
TI  - Antimicrobial photodynamic therapy: photodynamic antimicrobial effects of
      malachite green on Staphylococcus, enterobacteriaceae, and Candida.
AB  - OBJECTIVE: This study investigated in vitro the photodynamic antimicrobial
      effects of the photosensitizer malachite green on clinical strains of
      Staphylococcus, Enterobacteriaceae, and Candida. MATERIALS AND METHODS: Thirty
      six microbial strains isolated from the oral cavity of patients undergoing
      prolonged antibiotic therapy, including 12 Staphylococcus, 12 Enterobacteriaceae,
      and 12 Candida strains, were studied. The number of cells of each microorganism
      was standardized to 10(6) cells/mL. Twenty-four assays were carried out for each
      strain according to the following experimental conditions: gallium-aluminum
      arsenide laser and photosensitizer (n = 6, L+P+), laser and physiologic solution
      (n = 6, L+P-), photosensitizer (n = 6, L-P+), and physiologic solution (n = 6, L
      P-). Next, cultures were prepared on brain-heart infusion agar for the growth of
      Staphylococcus and Enterobacteriaceae, and on Sabouraud dextrose agar for the
      growth of Candida, and incubated for 48 h at 37 degrees C. The results are
      reported as the number of colony-forming units (CFU/mL) and were analyzed with
      analysis of variance and the Tukey test. RESULTS: The Staphylococcus,
      enterobacterial, and Candida strains were sensitive to photodynamic therapy with
      malachite green (L+P+). A reduction of approximately 7 log(10) for
      Staphylococcus, 6 log(10) for enterobacteria, and 0.5 log(10) for the genus
      Candida. Significant statistical differences were observed between the L+P+
      groups and the control groups (L-P-). CONCLUSION: The Staphylococcus,
      Enterobacteriaceae, and Candida strains studied were sensitive to photodynamic
      therapy with malachite green.

PMID- 20690841
TI  - Surgical research IV.
AB  - Harvey W. Cushing (1869-1939) is the only surgeon represented in Surgical
      Research IV and one of the most accomplished American contributors to surgical
      research in general and to neurological and endocrine surgery research in
      particular. Other surgical research leaders of the 19th and 20th centuries who
      preceded Harvey Cushing have been introduced before. First, we highlighted the
      "importance of medical and surgical research" as the basic elements in the
      advancement of medicine and surgery could be considered as Surgical Research I.
      Second, in Surgical Research II, we presented William Beaumont, Samuel Gross, and
      William Halsted as the most important participants of the first wave of American
      surgical researchers. Next, in Surgical Research III, we considered surgeon
      researchers who moved ahead in the field of surgery with their research
      initiatives at the time, including John B. Murphy, the Mayo Brothers William J.
      and Charles H. Mayo, and George W. Crile. With Harvey Cushing, we enter an era of
      surgical research associated with neurosurgery and endocrine surgery as part of
      Surgical Research IV.

PMID- 20690842
TI  - Effects of nitric oxide donor on hepatic arterial buffer response in anesthetized
      pigs.
AB  - The effects of systemic administration of exogenous nitric oxide (NO) donor on
      hepatic arterial buffer response (HABR) have not yet been studied in an
      anesthetized model. In this study, 28 anesthetized pigs received administration
      of sodium nitroprusside (SNP) or nitroglycerin (NTG) as exogenous NO donors.
      Pressure-flow (P-Q) relationships in the hepatic artery defined the pressure at
      zero flow (P(Qha = 0)) and flow-dependent resistance (R). The magnitude of HABR
      was evaluated by comparing the change in hepatic arterial blood flow (DeltaQha)
      divided by the change in portal venous blood flow (DeltaQpv), using the index of
      change in blood flow (DeltaQha/DeltaQpv). Mean arterial pressure decreased from
      baseline (95.6 +/- 3.8 mmHg) to SNP condition (68.3 +/- 1.9 mmHg) and decreased
      from baseline (92.7 +/- 4.4 mmHg) to NTG condition (66.2 +/- 1.7 mmHg). Mean
      index of change in blood flow (DeltaQha/DeltaQpv) was also significantly
      increased from baseline (0.19 +/- 0.12) to SNP condition (0.28 +/- 0.17; p =
      .009) and from baseline (0.18 +/- 0.17) to NTG (0.28 +/- 0.20; p < .05). In
      conclusion, systemic administration of SNP and NTG increases HABR with reduced
      hepatic arterial tone under decreased mean arterial pressure, presumably via
      exogenous NO enhancing another regulatory system and reducing the pressure
      gradient for sinusoidal washout.

PMID- 20690843
TI  - Large-pore PDS mesh compared to small-pore PG mesh.
AB  - BACKGROUND: Currently, absorbable meshes are used as temporary closure in case of
      laparostoma. Unfortunately the multifilament polyglycolic acid (PG) meshes with
      small pores reveal little elasticity acting rather as a fluid barrier than
      permitting drainage of intra-abdominal fluids. Therefore, a new mesh was
      constructed of absorbable polydioxanon monofilaments (PDS) with increased
      porosity and longer degradation time. MATERIAL AND METHODS: For evaluation of the
      tissue response the new PDS mesh was implanted as abdominal wall replacement in
      each five rats for 7, 21, or 90 days, respectively, and compared to a PG mesh.
      Histological analysis included HE staining with measurement of the size of the
      granuloma and immunoshistochemistry for TUNEL, Ki67, TNF-R2, MMP-2, YB1, FVIII,
      gas6, AXL. Parameters for neovascularization and nerve ingrowth were analyzed.
      RESULTS: The inflammatory and fibrotic tissue reaction is attenuated with PDS in
      comparison to PG, e.g., the size of the granuloma was smaller with less cell
      turnover, and less remodeling as represented by, e.g., reduction of apoptosis,
      expression of MMP-2, or TNF-R2. The number of ingrowing nerves and vessels
      explored via AXL, gas6, and factor VIII was increased in the PDS mesh.
      CONCLUSION: The results from the present investigation showed that a mesh can be
      constructed of monofilament PDS that induce significant less inflammatory and
      fibrotic reaction, however permits fluid drainage and preserves elasticity.

PMID- 20690844
TI  - Anastomotic leak detection by electrolyte electrical resistance.
AB  - OBJECTIVE: To characterize a new method of postoperative gastrointestinal leak
      detection based on electrical resistance changes due to extravasated electrolyte
      contrast. BACKGROUND: Postoperative gastrointestinal leak results in increased
      patient morbidity, mortality, and hospital costs that can be mitigated by early
      diagnosis. A sensitive and specific diagnostic test that could be performed at
      the bedside has the potential to shorten the time to diagnosis and thereby
      improve the quality of treatment. MATERIALS AND METHODS: Anaesthetized rats
      underwent celiotomy and creation of a 5-mm gastrotomy. In experimental animals,
      electrical resistance changes were measured with a direct current ohmmeter after
      the introduction of 5 cc of 23.4% NaCl electrolyte solution via gavage and
      measured with a more sensitive alternating current ohmmeter after the gavage of 1
      5 cc of 0.9% NaCl. Comparison was made to negative controls and statistical
      analysis was performed. RESULTS: Leakage from the gastrotomy induced by as little
      as 1 cc of gavage-delivered 0.9% NaCl contrast solution was detectable as a
      statistically significant drop in electrical resistance when compared to results
      from negative controls. CONCLUSION: Electrical resistance change associated with
      electrolyte-gated leak detection is highly sensitive and specific and has the
      potential to be rapidly translated into clinical settings.

PMID- 20690845
TI  - The effect of local use of nandrolone decanoate on rotator cuff repair in
      rabbits.
AB  - OBJECTIVE: There is still controversy about the effect of anabolic steroid on
      connective tissue. This study examines the hypothesis that the local use of
      nandrolone decanoate, an anabolic steroid on rotator cuff, facilitates the
      healing process when used in combination with surgical repair. METHODS: Forty
      eight male rabbits were divided in four groups with anabolic steroids (Nandrolone
      Decanoate 10 mg/kg) and immobilization as variables. The groups were the
      following: first group, nonsteroid use-immobilization (NSI); second group,
      nonsteroid use-nonimmobilization (NSNI); third group, steroid use-immobilization
      (SI); fourth group steroid use-nonimmobilization (SNI). Every rabbit underwent a
      rotator cuff incision and reconstruction. Fifteen days later the tendons were
      sent for biomechanical and histological evaluation. RESULTS: Groups that did not
      receive anabolic steroids showed better healing and more tendon strength in
      comparison to groups that received anabolic steroids. Microscopic examination of
      specimens from the groups without the use of anabolic steroid showed extensive
      fibroblastic activity whereas the specimens from those groups with anabolic
      steroid use showed focal fibroblastic reaction and inflammation. Immobilization
      provided better results in the groups with anabolic steroid use but it did not
      influence healing in groups without steroids. CONCLUSIONS: The effect of local
      nandrolone decanoate use on a rotator cuff tear is detrimental, acting as a
      healing inhibitor.

PMID- 20690846
TI  - Quantification of ischemia-reperfusion injury to the small intestine using a
      macroscopic score.
AB  - INTRODUCTION: Classical methods do not allow to rapidly quantify the
      heterogeneously distributed ischemia-reperfusion injury along the small
      intestine. We therefore established a suitable macroscopic score. METHODS: A rat
      model based on superior mesenteric artery occlusion (45 or 90 min ischemia; 0,
      120, or 180 min reperfusion) was used on 42 rats. RESULTS: Subsequent to ischemia
      reperfusion or pure ischemia, macroscopic phenotypes of the small intestine were
      defined and differentiated based on the severity of existing petechiae and
      hemorrhages (macroscopic types 0-1-2-3). Analysis of the interobserver
      variability verified the reliability of this macroscopic differentiation.
      Macroscopic types were directly correlated with their histological alterations
      (Chiu score). On the basis of the sample hemoglobin content, a nonlinear
      macroscopic score (0-1-3-9) was derived from the linearly related macroscopic
      types. Mean macroscopic scores after 45 min ischemia/180 min reperfusion were
      lower than those after 90 min ischemia/120 min reperfusion. Nevertheless, all
      scores correlated well with their respective hemoglobin contents (R(2) = 0.87).
      Heterogeneous patterns of macroscopic scores that depended on the ischemic period
      and largely differed between individual animals were found to be distributed
      along the small intestine with the highest injury score at the last half of the
      jejunum. The iron chelator deferoxamine mesylate clearly decreased the overall
      tissue hemoglobin content and macroscopic score of the small intestine but local
      protection was restricted to the proximal and middle part of the jejunum.
      CONCLUSION: The local as well as overall ischemia-reperfusion injury in the rat
      small intestine can be rapidly and reliably assessed macroscopically.

PMID- 20690847
TI  - The role of d-lactate in differential diagnosis of acute appendicitis.
AB  - INTRODUCTION: Early diagnosis of acute appendicitis, known as the most frequent
      cause of acute surgical abdominal pathologies, dramatically decreases the related
      complications. D-lactate, produced by intestinal bacteria as a fermentation
      product, may be useful in diagnosing acute abdominal pathologies. The aim of this
      study was to investigate whether the presence of d-lactate would be a significant
      indicator in the early diagnosis of acute appendicitis. METHODS: Eighty
      consecutive patients were prospectively included in this study. The patients were
      divided into four groups: acute appendicitis (group 1), perforated acute
      appendicitis (group 2), nonspecific abdominal pain (group 3), and acute abdomen
      other than acute appendicitis (group 4). For the control group, blood samples
      were taken in the same manner from 20 healthy subjects. RESULTS: There was no
      significant difference in blood d-lactate levels between the simple acute
      appendicitis and acute perforated appendicitis groups (p > .05). The blood d
      lactate levels in groups 1 and 2 were significantly higher than those in groups 3
      and 4, and the control group (p < .001). The reliability of d-lactate was
      determined as 97% sensitivity, 93% specificity, 90% positive predictive and 95%
      negative predictive values, and 95% accuracy. CONCLUSIONS: Based on findings in
      this study, blood d-lactate level may be a valuable diagnostic marker for the
      diagnosis of acute appendicitis.

PMID- 20690848
TI  - The benefits of ligating the lobar portal triads before partial hepatectomy in
      the mouse.
AB  - Partial hepatectomy in mice is a basic model for hepatic research work. Different
      complications, especially bleeding, bile leakage, and vena cava stenosis, have
      been observed with the classical technique, which features ligature en-bloc at
      the base of the hepatic lobes. In order to reduce complications and improve
      experimental outcome, a novel, rapid, and safe technique was developed, which was
      characterized by the ligation of the lobar portal triads before the lobes were
      resected. Compared with previous protocols, the new protocol was associated with
      much less complications and better survival rates, and can be easily and safely
      performed without microsurgical equipments and techniques.

PMID- 20690849
TI  - Intracellular calcium signaling pathways during liver ischemia and reperfusion.
AB  - Calcium plays a major role in intracellular signaling mechanisms during ischemia
      reperfusion (I/R) injury of a liver cell. Under ischemic conditions, the absence
      of oxygen arrests oxidative phosphorylation, thereby eliminating the energy
      source by which hepatocellular mechanisms maintain homeostasis of calcium. This,
      in turn, leaves nonselective plasma membrane influx pores unopposed and results
      in a net increase in intracellular calcium concentrations. Subsequent reperfusion
      marks the onset and progression of apoptosis and necrosis, as it involves
      inflammatory responses as well as free-radical formation due to re-oxygenation of
      cells. These processes destroy the structural integrity of organelles, leading to
      disruptive redistribution of calcium between cellular and subcellular
      compartments. This initial elevation and later imbalance of intracellular calcium
      concentrations associated with I/R induce various molecular responses within each
      organelle. In the cytoplasm, a series of pro-apoptotic pathways involving various
      calcium sensitive enzymes are activated. The injury is further exacerbated in the
      endoplasmic reticulum (ER) due to the malfunction of mechanisms responsible for
      intracellular calcium sequestration. Both the mitochondria and the nucleus are
      also adversely affected, as their structural integrity and physiologic functions
      are disrupted. To date, however, the precise pathophysiology of these calcium
      mediated signaling pathways is not fully understood due to its complex nature.
      This review aims to systematically examine the current literature about
      individual molecular signaling pathways in the cytoplasm, ER, mitochondria, and
      the nucleus prior to causing time-sensitive progression of permanent tissue
      injury.

PMID- 20690850
TI  - Ankaferd blood stopper for gastrointestinal bleeding.

PMID- 20690851
TI  - Surface and biomechanical study of titanium implants modified by laser with and
      without hydroxyapatite coating, in rabbits.
AB  - Surface and biomechanical analysis of titanium implant surfaces modified by laser
      beam with and without hydroxyapatite. Titanium implants with 3 different surfaces
      were inserted into the tibias of 30 rabbits: group I (GI) machined surface
      (control group), group II irradiated with laser (GII), and group III irradiated
      with laser and hydroxyapatite coating applied-biomimetic method (GIII).
      Topographical analysis with scanning electron microscopy was made before surgery
      in the tibia. These rabbits were distributed into 2 periods of observation: 4 and
      8 weeks postsurgery, after which biomechanical analysis (removal torque) was
      conducted. Statistical analysis used the Student-Newman-Keuls method. Surface
      showed roughness in GII and GIII. Biomechanical analysis demonstrated values with
      significant differences in GII and GIII. Titanium implants modified by laser
      irradiation can increase osseointegration during the initial phase.

PMID- 20690852
TI  - Chair-side fabrication of a fixed implant-supported prosthesis in an edentulous
      mandible from a diagnostic wax-up: a clinical report.

PMID- 20690853
TI  - Simplifying the implant treatment plan for an elderly patient.

PMID- 20690854
TI  - Radiologic evaluation of putty versus powder form of demineralized bone matrix in
      sinus floor elevation.
AB  - The aim of this study was to evaluate differences in ossification of the 2 forms
      of demineralized bone matrix (DBM)-putty and powder-radiographically, using
      digital densitometry on panoramic radiographs in maxillary sinus floor
      augmentation procedures. Twelve subjects needing bilateral maxillary sinus floor
      augmentation for the placement of osseointegrated implants were included in this
      study. The left and right maxillary sinuses were augmented in the same session in
      each patient using the 2 preferred forms of DBM-putty and powder-during the same
      session. One sinus was augmented with DBM putty form and the other sinus was
      augmented with DBM powder form randomly. Every patient had a total of 4 panoramic
      radiographs taken, preoperatively and in the first, third, and sixth month
      postoperatively. The densitometry measurements were taken from each step of the
      aluminium step-wedge, from both sinuses from different points a total of 3 times,
      and the average of these measurements was calculated. The amount of
      mineralization in each graft material in every radiograph was clarified by the
      appearance of a difference in the equivalent aluminium thickness, and the
      obtained results were statistically evaluated. The results showed that there were
      no significant differences between two graft materials statistically. These two
      graft materials could be good alternatives in sinus lifting procedures because of
      less morbidity, lower price, and good ossification. The results indicate that 2
      different types of DBM achieved good ossification in the sinus lifting procedure,
      and there is not a considerable distinction in these 2 forms.

PMID- 20690855
TI  - Simple diagnostic method to assess the available bone for immediate implant
      placement in an extracted socket.
AB  - The success rate of immediate tooth replacement has been well documented in the
      literature. To achieve long-term success of dental implants, evaluation of the
      dimensions of the resorbing alveolar process must be accurate because an implant
      should be surrounded by at least 1 mm of bone. To minimize facial gingival
      recession, an intact labial bony plate along with an osseous-gingival
      relationship of 3 mm on the facial aspect of the failing tooth has been
      suggested. This article mentions a technique wherein the amount of available
      labial and palatal bone of an extracted socket can be assessed by using the
      extracted tooth that is to be replaced with an endosseous implant and a ridge
      mapping procedure without reflecting the flap.

PMID- 20690857
TI  - Health-related quality of life in patients with cryptogenic polyneuropathy
      compared with the general population.
AB  - PURPOSE: To evaluate the quality of life (QOL) in patients with cryptogenic
      polyneuropathy. METHOD: Two validated instruments (SF-36 and EQ-5D) were sent to
      86 patients with a 72% response rate (44 men, 18 women). As reference, 2721
      individuals (1292 men, 1429 women; 59% response rate) from the general population
      responded to the same QOL instruments. RESULTS: Compared to the general
      population, QOL was significantly more affected in patients with polyneuropathy
      concerning motor functions, with 42% of the patients reporting problems with
      walking, 7% having difficulties with washing and dressing, and 31% having
      problems with usual activities (work, study, household work, and family or
      leisure activities). The EQ-5D results showed that 85% of the patients were
      suffering from pain compared to 56% of the general population. Mental health was
      preserved among patients with polyneuropathy. Mobility was declining with
      increasing age in patients, but was not affected by disease duration.
      CONCLUSIONS: Our study showed that patients with cryptogenic polyneuropathy have
      a lower QOL compared to the general population, although mental health scores did
      not differ between the groups. This information may be helpful when explaining
      the disease and its impact on newly diagnosed patients.

PMID- 20690856
TI  - Regulation of homologous recombination in eukaryotes.
AB  - Homologous recombination (HR) is required for accurate chromosome segregation
      during the first meiotic division and constitutes a key repair and tolerance
      pathway for complex DNA damage, including DNA double-strand breaks, interstrand
      crosslinks, and DNA gaps. In addition, recombination and replication are
      inextricably linked, as recombination recovers stalled and broken replication
      forks, enabling the evolution of larger genomes/replicons. Defects in
      recombination lead to genomic instability and elevated cancer predisposition,
      demonstrating a clear cellular need for recombination. However, recombination can
      also lead to genome rearrangements. Unrestrained recombination causes undesired
      endpoints (translocation, deletion, inversion) and the accumulation of toxic
      recombination intermediates. Evidently, HR must be carefully regulated to match
      specific cellular needs. Here, we review the factors and mechanistic stages of
      recombination that are subject to regulation and suggest that recombination
      achieves flexibility and robustness by proceeding through metastable, reversible
      intermediates.

PMID- 20690858
TI  - Depression in acute stroke: prevalence, dominant symptoms and associated factors.
      A systematic literature review.
AB  - PURPOSE: The aim of this review was to provide a comprehensive analysis of the
      state of knowledge about post-stroke depression (PSD) in the acute phase,
      focusing on: (a) the prevalence of depressive disorder and depressive symptoms,
      (b) the dominant depressive symptoms, (c) the factors associated with PSD and (d)
      the follow-up consequences. METHOD: A computer-aided search in MEDLINE, CINAHL,
      PsychInfo, EMBASE, British Nursing index, Pub Med and Ovid Nursing Database was
      performed. We systematically searched for studies including depression within the
      first month after stroke. RESULTS: Forty articles including more than 5400
      informants from 37 cohorts met the inclusion criteria. Only a few studies aimed
      to describe the nature of PSD. The prevalence of depressive disorder and
      depressive symptoms in the acute phase ranged widely from 5% to 54%. Multiple
      tools were used for measuring depressive symptoms in the acute phase. An
      association was found between early depressive symptoms and the continuation of
      PSD 12 months after stroke. There is a correlation between depressive symptoms
      and mortality at 12 and 24 months. CONCLUSION: Depressive symptoms are common in
      the acute phase after stroke and associated with persistency of depression and
      mortality after 12 months. A gold standard for the measurement of depressive
      symptoms in relation to stroke is missing. The knowledge of PSD in the acute
      phase is still limited, and there is a need for continued empirical research on
      its profile and patterns.

PMID- 20690859
TI  - Return or no return--psychosocial factors related to sick leave in persons with
      musculoskeletal disorders: a prospective cohort study.
AB  - PURPOSE: The aim of this study was to compare psychosocial factors between
      healthy persons and sick-listed persons with musculoskeletal disorders (MSD);
      both groups with MSD 10 years ago. METHODS: This cohort study was prospective and
      385 persons participated in a rehabilitation program 10 years ago, and 354
      persons took part in the follow-up. Of these, 243 persons completed a
      questionnaire. Two groups were included in the study: a healthy group (not sick
      listed) (n = 112) and a sick-listed group (n = 74). Psychosocial factors related
      to sick leave were compared between the groups. RESULTS: In the 10-year follow
      up, the healthy group showed a significantly higher quality of life, more control
      over the working situation, better sense of coherence and unexpectedly more life
      events. There was no significant difference in social integration and emotional
      support between the groups. CONCLUSIONS: Using the knowledge about the
      characteristics of the healthy group, adequate rehabilitation for every sick
      listed person with a musculoskeletal disorder can be given and therefore
      facilitate the returning to work process. A multidimensional approach taking into
      account a person's physical condition and workplace related problems, as well as
      psychosocial factors, is of great importance for the person and for society.

PMID- 20690860
TI  - When East meets Wests: community-based rehabilitation in Chinese communities.
AB  - PURPOSE: Community-based rehabilitation (CBR) has been practiced in mainland
      China for over three decades. This study reviews the development of CBR and
      describes its practice in Chinese communities in order to discuss current
      controversies within CBR practice internationally and in the Chinese context.
      METHOD: Review of literature. Development of CBR, its principles and
      controversies internationally and in the Eastern world is reviewed. CBR practice
      in Chinese communities is examined. RESULTS: Shifting ideology and practices mean
      many different activities are labelled CBR. Variation across contexts has led to
      many controversies, specifically: the lack of evidence to support practice;
      ownership of programs; conceptual differences surrounding autonomy and
      participation and cultural issues. Contemporary Chinese cultural values and
      Chinese CBR are shaped by traditional peasant culture, traditional Chinese
      philosophy and socialist ideology. CONCLUSION: The review indicates that Western
      CBR concepts and philosophy cannot be directly applied to the Chinese context. An
      appropriate model or framework is needed to fit the unique Chinese cultural
      context and to guide practice in Chinese communities.

PMID- 20690861
TI  - Measuring leprosy-related stigma - a pilot study to validate a toolkit of
      instruments.
AB  - PURPOSE: Stigma negatively affects the quality of life of leprosy-affected
      people. Instruments are needed to assess levels of stigma and to monitor and
      evaluate stigma reduction interventions. We conducted a validation study of such
      instruments in Tamil Nadu and West Bengal, India. METHODS: Four instruments were
      tested in a 'Community Based Rehabilitation' (CBR) setting, the Participation
      Scale, Internalised Scale of Mental Illness (ISMI) adapted for leprosy-affected
      persons, Explanatory Model Interview Catalogue (EMIC) for leprosy-affected and
      non-affected persons and the General Self-Efficacy (GSE) Scale. We evaluated the
      following components of validity, construct validity, internal consistency, test
      retest reproducibility and reliability to distinguish between groups. Construct
      validity was tested by correlating instrument scores and by triangulating
      quantitative and qualitative findings. Reliability was evaluated by comparing
      levels of stigma among people affected by leprosy and community controls, and
      among affected people living in CBR project areas and those in non-CBR areas.
      RESULTS: For the Participation, ISMI and EMIC scores significant differences were
      observed between those affected by leprosy and those not affected (p = 0.0001),
      and between affected persons in the CBR and Control group (p < 0.05). The
      internal consistency of the instruments measured with Cronbach's alpha ranged
      from 0.83 to 0.96 and was very good for all instruments. Test-retest
      reproducibility coefficients were 0.80 for the Participation score, 0.70 for the
      EMIC score, 0.62 for the ISMI score and 0.50 for the GSE score. CONCLUSION: The
      construct validity of all instruments was confirmed. The Participation and EMIC
      Scales met all validity criteria, but test-retest reproducibility of the ISMI and
      GSE Scales needs further evaluation with a shorter test-retest interval and
      longer training and additional adaptations for the latter.

PMID- 20690862
TI  - Design of built environments to accommodate mobility scooter users: part I.
AB  - PURPOSE: To determine the minimum dimensions needed to allow five models of
      powered mobility scooters to manoeuvre within five commonly encountered indoor
      spatial configurations. METHOD: We measured manoeuvrability of five scooters
      judged by their manufacturers to have a good combination of indoor mobility and
      outdoor performance (including in rural environments). We determined the minimum
      space needed to manoeuvre the scooters through the following five spatial
      configurations: turning 180 degrees  in a corridor, performing U-turns around 50
      mm (2") and 1200 mm (4') obstacles, turning 90 degrees  from a doorway and
      approaching a counter or work surface from the side. Free-standing styrofoam
      walls were used to define each configuration. An expert driver repeatedly
      manoeuvred the scooters through each configuration while we incrementally
      decreased the dimension of interest until it was no longer possible to complete
      the manoeuvre. Each scooter's turning diameter was also measured and compared to
      the manufacturer's specification. RESULTS: Minimum space requirements for each
      scooter for five spatial configurations are given and compared to existing
      standards. CONCLUSIONS: None of the scooters tested were capable of completing
      all manoeuvres within the space allowed by existing standards. These findings
      will contribute to recommendations for new standards for built environments that
      can accommodate scooter users.

PMID- 20690863
TI  - Measurement of muscle stiffness using robotic assisted gait orthosis in children
      with cerebral palsy: a proof of concept.
AB  - PURPOSE: To evaluate the feasibility and reliability of a novel stiffness
      assessment tool implemented in the driven gait orthosis Paediatric Lokomat; to
      investigate the influence of single robotic-assisted gait training (RAGT) on
      muscle stiffness in children with cerebral palsy (CP). METHODS: Ten children with
      spastic CP conducted a single standard RAGT session and stiffness was assessed
      before and after the RAGT. Nine of the ten subjects were tested twice on the same
      day to investigate test-retest reliability, intraclass correlation coefficients
      (ICCs), standard error of measurement (SEM), coefficient of variation of the
      method error (CV(ME)) and resistive torques during passive leg movements
      (stiffness in Nm/ degrees ) were calculated. RESULTS: ICCs showed high
      reliability (0.83-0.97) for hip and knee movements. SEM and CV(ME) indicated
      0.028-0.085 Nm/ degrees , 9.5-23.0% of test-retest variability in hip and 0.018
      0.064 Nm/ degrees , 13.3-43.5% in knee measures. Using the assessment tool, a
      significant decrease in muscle stiffness in participants, especially in children
      with high levels of muscle tone, could be shown after a single session of RAGT.
      CONCLUSIONS: The assessment tool L-STIFF is a feasible tool for automated
      measurement of stiffness in children with CP, but it is not sensitive enough to
      record small changes in muscle tone.

PMID- 20690864
TI  - Uterine prolapse: evaluation of glycosaminoglycans in postmenopausal women after
      estrogen therapy.
AB  - OBJECTIVE: To evaluate glycosaminoglycans (GAGs) in the parametrium, paraurethral
      tissue and vaginal apex in postmenopausal women with uterine prolapse and to
      evaluate the effect of 30-day estrogen therapy in these patients. MATERIAL AND
      METHODS: Double-blind trial of estrogen and placebo in 40 women with a control
      group of 20 premenopausal women without uterine prolapse. Twenty postmenopausal
      women with prolapse formed a second group and were treated with placebo for 30
      days before vaginal hysterectomy. The third group included 20 postmenopausal
      women with prolapse who received 0.625 mg oral conjugated estrogens for 30 days
      before vaginal hysterectomy. Samples of the parametrium, vaginal apex and
      paraurethral tissue were obtained during surgery. RESULTS: Hyaluronic acid was
      the predominant GAG detected, followed by dermatan sulfate, chondroitin sulfate
      and heparan sulfate. In postmenopausal women with prolapse, we did not observe
      significant differences in total GAGs compared to the control group. However,
      hyaluronic acid was increased in the parametrium of women receiving estrogen
      compared to those treated with the placebo (2033.39 +/- 3037.90 mg/g vs. 587.87
      +/- 697.89 mg/g, respectively; p = 0.041). CONCLUSIONS: There are differences in
      GAGs in the parametrium, paraurethral tissue and vaginal apex between women in
      premenopause and those in the postmenopause period. Therefore, 30-day estrogen
      therapy produces significant differences in levels of hyaluronic acid, dermatan
      sulfate and chondroitin sulfate.

PMID- 20690865
TI  - Effect of tibolone on audiologic functions in menopausal women.
AB  - OBJECTIVE: The aim of this study was to examine the effect of tibolone on hearing
      function in postmenopausal women. METHODS: This prospective study involved 60
      postmenopausal women. Participants were randomly divided into two groups. The
      tibolone group was assigned to receive a tibolone tablet daily (n = 30). The
      other 30 cases who had not received any kind of hormone therapy were taken as the
      control group. The hearing levels of both ears in all women were measured by
      audiometry before initiation of tibolone therapy and 6 months after therapy.
      RESULTS: The baseline hearing threshold levels of the two groups were similiar.
      After 6 months, audiometry results did not differ from baseline levels in the
      control group. In the tibolone group, there was some improvement in almost all
      hearing threshold levels after therapy. Statistically significant differences
      were only observed on the right side at pure tone audiometry and at the 500 and
      6000 Hz levels. CONCLUSIONS: Although tibolone has both gestagenic and androgenic
      properties together with estrogenic properties, no negative effect on hearing
      after 6 months of treatment was observed. On the contrary, there was significant
      improvement in audiometry results at low frequencies after 6 months' treatment.
      Although statistically not significant, there was some improvement at high
      frequencies.

PMID- 20690866
TI  - Periodontitis and osteoporosis: a systematic review.
AB  - BACKGROUND: Osteoporosis and periodontitis are frequent disorders that affect
      aging populations. It has been hypothesized that both conditions may be related.
      OBJECTIVE: To determine whether dental osteoporosis is a local manifestation of
      systemic bone loss having similar etiology and risk factors, or whether it is an
      independent process depending primarily on factors that cause periodontitis.
      METHODS: A systematic review of clinical trials assessing the relationship
      between osteoporosis and periodontitis was carried out. An electronic search was
      made based on Internet search engines, MEDLINE (from 1966 to December 2009) and
      the Cochrane Controlled Clinical Trials Register. RESULTS: A total of 145 studies
      dealing with the relationship osteoporosis-periodontitis were identified. Of
      them, 35 were considered suitable for selection. Studies on maxillary and/or
      mandible radiological findings have a positive correlation in the majority of the
      cases (18 positive vs. three negative), whereas the findings on clinical
      periodontal examination are inconclusive (six positive vs. five negative). There
      were ten studies in which a diagnosis of osteoporosis was made, based on the
      existence of non-traumatic fracture, while there were nine studies using
      radiographs for diagnosis, of which six studies were found to have a positive
      correlation. There was only one study based on a clinical periodontal examination
      that found a positive correlation. CONCLUSIONS: The majority of the studies
      suggested a relationship between osteoporosis and periodontitis. Further well
      controlled studies are needed to better elucidate the inter-relationship between
      systemic and oral bone loss and to clarify whether dentists could usefully give
      an early warning for osteoporosis risk.

PMID- 20690867
TI  - Education and information: important tools in assessing the risks and prevention
      of osteoporosis fractures.
AB  - The recent results of the Global Longitudinal Study of Osteoporosis in Women on
      the lack of self-perceived risk of fracture are just one set of a series of
      publications that will contribute to the enhancement of osteoporosis assessment
      and perception and will help to develop new and specific interventions for
      fracture prevention and ultimately decrease mortality secondary to fractures. The
      failure of women to appreciate their own risk of fracture is a barrier to
      receiving appropriate care and safe and effective treatments. The study
      demonstrates that increased efforts must be made to educate medical professionals
      and the public including women of any age about the risks of fracture. The
      importance of osteopenia, osteoporosis and their impact on fractures should be
      well defined and emphasized, the notion of risk of fracture and its main causes
      at any age should be explained, and protective factors and lifestyle that may
      improve the overall health and reduce this risk for osteoporosis and fractures
      should be presented in an appropriate manner for each age and level of education.
      The first results of this large-scale study showed the lack of self-perceived
      risk of fracture 'in women and by women' of 55 years or older. Action for
      prevention should be taken by the women who are already at this age but also by
      the women who will soon reach this age.

PMID- 20690868
TI  - Age of menopause and impact of climacteric symptoms by geographical region.
AB  - OBJECTIVE: To describe differences in the age of onset of menopause and in the
      prevalence of climacteric symptoms in different geographical areas. DESIGN:
      Systematic review of published data on onset of menopause and symptoms in Europe,
      North America, Latin America and Asia. METHODS: We identified publications by
      searching electronic databases, including MEDLINE (1966-October 2009) and EMBASE
      (1975-October 2009). Primary search criteria were age of menopause and
      climacteric symptoms. A sensitive analysis that excluded papers without full data
      was performed. RESULTS: The median age at menopause in Europe ranges from 50.1 to
      52.8 years, in North America from 50.5 to 51.4 years, in Latin America from 43.8
      to 53 years, and in Asia from 42.1 to 49.5 years. The frequency of vasomotor
      symptoms varies widely depending on the geographical region, selection of
      criteria, and method of symptom identification. The prevalence of such symptoms
      ranges from 74% of women in Europe, 36-50% in North America, 45-69% in Latin
      America and 22-63% in Asia, as reported in different, large, epidemiological
      studies. CONCLUSION: There are wide geographical differences in the prevalence of
      menopausal symptomatology and some differences in the age of onset of menopause.
      Both in Asia and Latin America, women of poorer socioeconomic status have
      significantly earlier onset of menopause. Within a geographical region, there are
      ethnic differences in menopause symptoms. Given differences in study
      methodologies, firm conclusions are not possible. However, regional differences
      in age at menopause and in climacteric symptoms are important to acknowledge and
      lay the foundation for an informed approach to the management of menopause and an
      understanding of its impact on women's health in the different regions of the
      world.

PMID- 20690869
TI  - Effect of stretch positions on hamstring muscle length, lumbar flexion range of
      motion, and lumbar curvature in healthy adults.
AB  - Hamstring stretching is a common practice in physical therapy to change not only
      hamstring muscle length (HML), but also lumbar flexion range of motion (LROM) or
      lumbar curvature (LC). Yet limited published research compares the effectiveness
      of two commonly used hamstring stretch positions, sitting and standing. The
      purposes of this study were to determine the effect of (1) stretch position on
      HML; and 2) HML on LROM and LC. Thirty-six participants (M=44.8 years, SD=17.1)
      with short HML (i.e., with shortness for men >=45 degrees  and for women >= 24
      degrees  of active knee flexion with 90 degrees  hip flexion) were measured for
      HML, LROM, and LC; randomly allocated to one of three groups: (1) hamstring
      stretching in sitting (SI); (2) standing (ST); or (3) no stretching (control);
      and remeasured after 4 weeks. Participants in the stretching groups performed two
      30-second static stretches 4 days per week for 4 weeks. Multivariate analysis of
      covariance (MANCOVA) showed significance between the stretching groups and
      nonstretching group for HML only. Nonsignificance was shown for HML between the
      stretch positions (i.e., SI-active knee extension (AKE) and ST-AKE), indicating
      that both were equally effective for increasing HML. However, there was no change
      in LROM or in LC even though HML increased.

PMID- 20690871
TI  - Interrater and intrarater reliability of ultrasonographic measurements of
      acromion-greater tuberosity distance in healthy people.
AB  - Acromion-greater tuberosity (AGT) distance could potentially be used to assess
      rotator cuff tears and shoulder subluxation in patients with poststroke
      hemiplegia. The aim of this study was to assess the interrater and intrarater
      reliability of ultrasonographic measurements of AGT distance in healthy people
      prior to testing on patient populations. Twenty healthy individuals (9 male, 11
      female) with a mean age of 21 years (SD +/- 2) were recruited. Three final year
      physiotherapy students (mean age 23 years) recorded the ultrasonographic
      measurements of AGT distance by using a standardised protocol. Reliability was
      assessed by intraclass correlation coefficients (ICC) and standard error of
      measurements (SEM). The mean AGT distances, as measured by rater one, two, and
      three were 2.24 +/- 0.45 cm, 2.27 +/- 0.37 cm, and 2.21 +/- 0.31, respectively.
      The interrater reliability coefficient was ICC = 0.79, and the intrarater
      reliability coefficients were 0.88, 0.84, and 0.91 for each rater. The SEM for
      the AGT distance measurements was ?0.15?cm for all three raters. Ultrasonographic
      measurements of AGT distance demonstrate good intrarater and interrater
      reliability in healthy individuals even when measured by three relatively
      inexperienced raters. It has potential to provide quantitative measurements for
      the clinical management of pathologies such as poststroke shoulder subluxation
      and rotator cuff tears.

PMID- 20690870
TI  - Effects of physiotherapeutic TENS in a woman with unexplained infertility.
AB  - Unexplained infertility (UI) is a difficult diagnosis in the field of obstetrics
      and gynaecology. This report describes TENS treatment as an adjunct therapy for a
      30-year-old woman with long-standing UI who was scheduled to undergo ovarian
      stimulation for in vitro fertilization (IVF) and embryo transfer. She had three
      unsuccessful intrauterine insemination treatments. Her last IVF treatment also
      failed. The treatment consisted of burst-TENS for seven sessions, which was
      applied daily from the second day of induction of ovulation (IO) to hCG
      administration. The transvaginal ultrasonography with pulsed Doppler curves was
      performed to measure the uterine artery impedance indices of Pulsatility Index
      (PI) and Resistance Index (RI). Before TENS application, on the first day of IO,
      the PI and RI for right side uterine artery were 3.96 and 0.96, respectively. For
      left uterine artery, the PI and RI were 6.92 and 1, respectively. After treatment
      with TENS, on the day of hCG administration, the PI and RI for right side uterine
      artery were 3.39 and 0.90, respectively. On the left side, they were PI=2.62 and
      RI=0.86. IVF was performed and on the day of oocytes collection, 22 oocytes were
      collected and inseminated. Fertilization was confirmed 16 hours after
      insemination by visualization of 2 pronuclei. A singleton pregnancy was achieved
      by the presence of a fetal sac during an ultrasound examination. It is concluded
      that the addition of TENS resulted in remarkable reduction of uterine artery PI
      and RI and a successful pregnancy after IVF for this woman with UI.

PMID- 20690872
TI  - The reliability and minimal detectable change of shoulder mobility measurements
      using a digital inclinometer.
AB  - The present study investigated the intrarater reliability, interrater reliability
      and minimal detectable change at the 90% confidence interval (MDC90) of active
      shoulder range of motion measurements using digital inclinometry. Two
      investigators each measured two repetitions of active flexion, abduction,
      external rotation (ER), and internal rotation (IR) on the nondominant shoulder of
      30 asymptomatic participants in a blinded repeated measures design. Results
      indicated good intrarater reliability with Intraclass Correlation Coefficients
      (ICCs) (3, k) of Flexion=0.83, Abduction=0.91, ER=0.94 and IR=0.87. Interrater
      ICC values (2, k) were moderate to good with Flexion=0.58, Abduction=0.95,
      ER=0.88 and IR=0.93. The MDC90 for the interrater analysis indicated that a
      change of equal to or greater than 8 degrees  (Flexion), 4 degrees  (Abduction),
      8 degrees  (IR), and 9 degrees  (ER) would be required to be 90% certain that the
      change is not due to intertrial variability or measurement error. Digital
      inclinometry appears to be a reliable instrument for quantifying normal shoulder
      mobility when strict measurement protocols are adhered to. Clinicians and
      researchers should consider the MDC values presented when interpreting change
      values during subsequent measurement sessions.

PMID- 20690873
TI  - The L.A. Brace-Description and discussion.
AB  - The L.A. Brace represents a new asymmetrical computer-generated full-time
      scoliosis brace used in the treatment of idiopathic scoliosis that uses the new
      system of algorithm-generated predictions for its data acquisition phase. Initial
      results suggest the L.A. Brace is an effective alternative brace treatment for
      scoliosis that provides an accurate cost-effective data acquisition system.

PMID- 20690874
TI  - Computer-aided design and computer-aided manufacture (CAD/CAM) system for
      construction of spinal orthosis for patients with adolescent idiopathic
      scoliosis.
AB  - ABSTRACT Spinal orthoses are commonly prescribed to patients with moderate
      adolescent idiopathic scoliosis (AIS) for prevention of further curve
      deterioration. In conventional manufacturing method, plaster bandages are used to
      obtain the patient's body contour and then the plaster cast is rectified
      manually. With computer-aided design and computer-aided manufacture (CAD/CAM)
      system, a series of automated processes from body scanning to digital
      rectification and milling of the positive model can be performed in a fast and
      accurate fashion. The purpose of this manuscript is to introduce the application
      of CAD/CAM system to the construction of spinal orthosis for patients with AIS.
      Based on evidence within the literature, CAD/CAM method can achieve similar
      clinical outcomes but with higher efficiency than the conventional fabrication
      method. Therefore, CAD/CAM method should be considered a substitute to the
      conventional method in fabrication of spinal orthoses for patients with AIS.

PMID- 20690875
TI  - Physical therapy management of a patient with Eagle syndrome.
AB  - The purpose of this care report was to describe the physical therapy management
      of a unique case involving a 50-year-old white female with complaints pertaining
      to the craniofacial, cervical, thoracic, and brachial regions with known Eagle
      syndrome as a complicating factor. Intervention consisted of manual therapy and
      therapeutic exercises. The Craniocervical Flexion Test (CCFT), Neck Disability
      Index (NDI), and subjective complaints were used as outcome measures. The patient
      was tested at initial visit, discharge, and at a 3-month follow-up. At discharge
      the patient reported complete cessation of craniofacial symptoms, her CCFT score
      had improved by 4 mmHg, and the NDI score had improved by 10%. At the 3-month
      follow-up, the patient's CCFT had improved an additional 4 mmHg and the NDI score
      had declined by 4%. The cumulative outcomes were an 8 mmHg improvement in the
      CCFT and a 6% increase on the NDI. Although subjective complaints and CCFT scores
      improved, clinically significant improvement with the NDI was not maintained.
      Limitations of this case study include the substitution of standardized equipment
      for the CCFT and the presence of numerous comorbidities that possibly influenced
      results. Further research is necessary.

PMID- 20690876
TI  - Multilevel lumbar fusion and postoperative physiotherapy rehabilitation in a
      patient with persistent pain.
AB  - There are no comparative randomised controlled trials of physiotherapy modalities
      for chronic low back and radicular pain associated with multilevel fusion.
      Physiotherapy-based rehabilitation to control pain and improve activation levels
      for persistent pain following multilevel fusion can be challenging. This is a
      case report of a 68-year-old man who was referred for physiotherapy intervention
      10 months after a multilevel spinal fusion for spinal stenosis. He reported high
      levels of persistent postoperative pain with minimal activity as a consequence of
      his pain following the surgery. The physiotherapy interventions consisted of
      three phases of rehabilitation starting with pool exercise that progressed to
      land-based walking. These were all combined with transcutaneous electrical nerve
      stimulation (TENS) that was used consistently for up to 8 hours per day. As
      outcome measures, daily pain levels and walking distances were charted once the
      pool programme was completed (in the third phase). Phase progression was
      determined by shuttle test results. The pain level was correlated with the
      distance walked using linear regression over a 5-day average. Over a 5-day moving
      average, the pain level reduced and walking distance increased. The chart of
      recorded pain level and walking distance showed a trend toward decreased pain
      with the increased distance walked. In a patient undergoing multilevel lumbar
      fusion, the combined use of TENS and a progressive walking programme (from pool
      to land) reduced pain and increased walking distance. This improvement was
      despite poor medication compliance and a reported high level of postsurgical
      pain.

PMID- 20690878
TI  - Implementing one standardized rehabilitation protocol following autologous
      chondrocyte implantation or microfracture in the knee results in comparable
      physical therapy management.
AB  - OBJECTIVE: The major aim of the study was (1) to compare the physiotherapy
      management in patients treated with autologous chondrocyte implantation (ACI)
      versus microfracture (MF) at the knee using a standardized rehabilitation
      protocol; and (2) to investigate the effect of activities in low-load conditions
      after surgery on the functional recovery was explored. DESIGN: 95
      physiotherapists received a standardized rehabilitation protocol that was used in
      a randomized controlled trial. A secondary analysis on patients' outcome was
      studied in a cohort design. OUTCOME MEASURES: An electronic report form including
      18 physiotherapy variables was used to compare physiotherapy management.
      Patients' functional outcome was assessed using the KOOS (Knee Injury
      Osteoarthritis Outcome Score) and the pooled symmetry index (SI) based on one
      strength and three hop tests. Both subjective and objective outcomes were
      evaluated pre-surgery, and at 1 and 2 years post-surgery. RESULTS: 65
      physiotherapists adhered very consistently to the protocol during the first 3
      months and showed a similar preference and timing for the physiotherapy
      modalities in both treatment groups. Patients with high amount of low-load
      activities (LLA+, n=21) post-surgery performed significantly better compared to
      patients with low amount of LLA (LLA-, n=17). At 24 months the mean pooled SI of
      LLA+ cohort was 92.4 compared to 78.2 for LLA- cohort (95% confidence interval
      [CI] 1.8 to 26.2). CONCLUSION: Overall, the compliance post-surgery with the
      rehabilitation protocol was excellent and the applied rehabilitation was
      comparable in both treatment groups. A high amount of low-load activities post
      surgery appears beneficial for the objective functional outcome.

PMID- 20690877
TI  - Feasibility and preliminary effectiveness of preoperative therapeutic exercise in
      patients with cancer: a pragmatic study.
AB  - The aim of this pilot study is to determine the feasibility and preliminary
      effectiveness of an individually designed preoperative therapeutic exercise
      program (PreTEP), in patients recently diagnosed with cancer and awaiting
      elective surgery. The purpose is to improve their physical fitness levels during
      this waiting period with the intention of decreasing postoperative morbidity. A
      preexperimental pilot study was performed at the University Medical Center
      Utrecht, The Netherlands. Thirty-nine patients diagnosed with cancer, scheduled
      for elective abdominal/thoracic surgery, were referred to a multidisciplinary
      preoperative screening. Fifteen patients (38%) participated in PreTEP.
      Participants were satisfied and motivated during the period of training (on
      average 5 weeks) in which they attended 84% of the sessions. Cardiorespiratory
      fitness (A strand-test) and muscle strength (Handheld Dynamometry) increased
      significantly, from 25 to 33 mL/kg/min, respectively (p<0.01; 95% confidence
      interval [CI]=-0.011 to -0.004) and from 894 Newton (N) to 961N (p<0.01; 95% CI=
      94.53 to -39.0). No adverse events occurred during the training period. PreTEP
      was shown to be feasible, safe, and well-tolerated and appreciated by
      participants. Despite the relatively short period of training, physical fitness
      improved in all participants.

PMID- 20690879
TI  - Monophasic electrical stimulation produces high rates of adverse skin reactions
      in healthy subjects.
AB  - Monophasic pulsed electrical stimulation (PES) has been reported to improve pain
      and function in osteoarthritis of the knee with few side effects. This use of
      monophasic current is contrary to conventional thinking where it is often
      associated with adverse skin reactions. The objectives of this study were to
      compare the rates of adverse skin reactions, using independently developed
      subsensory monophasic PES in healthy subjects, with those described in previous
      studies and compare the rate of adverse skin reactions after using the monophasic
      PES with that after using the same shaped electrical waveform that is
      asymmetrically biphasic. Healthy subjects (n=25) with no contraindications to
      electrical stimulation were administered subsensory, monophasic, and biphasic PES
      sequentially to the knee region for approximately 10 minutes each. Stimulation
      intensities; duration of stimulation; description of sensation reported; skin
      condition after intervention; and duration of skin reaction were all recorded.
      Fifty-two percent of subjects experienced adverse skin reactions using monophasic
      PES. This was significantly different from the reported rates in three of the
      four previous studies (p<0.04). Only one subject (4%) using the biphasic current
      demonstrated an adverse skin reaction. Results support the caution advised in the
      electrotherapy literature when using monophasic electrical stimulation.

PMID- 20690880
TI  - Work-related musculoskeletal disorders in female Swedish physical therapists with
      more than 15 years of job experience: prevalence and associations with work
      exposures.
AB  - The objective of this study was to determine the prevalence of and risk factors
      for work-related musculoskeletal disorders (WRMDs) in female physiotherapists
      with more than 15 years of job experience. A self-administered postal
      questionnaire was sent to 203 female physiotherapists with more than 15 years of
      job experience. Unconditional logistic regression was used to study the
      association between job exposures and the risk for WRMDs. The questionnaire was
      returned by 131 physiotherapists (64.5%). Of 99 subjects who answered specific
      questions about WRMDs, 52 (53.5%) were affected by WRMDs in at least one body
      part. Regions most affected were the hand/wrist (n=31; 58.5%) and the lower back
      (n=30; 56.5%). For hand/wrist pain, associations were found with: orthopedic
      manual therapy techniques (adjusted odds ratio [OR]=3.90; 95% confidence interval
      [CI]=1.2-13.1); working in awkward or cramped positions (OR=4.96; 95% CI=1.3
      18.7); and high psychological job demands (OR=4.34; 95% CI=1.2-15.0). For lower
      back pain, associations were found with: working in awkward or cramped positions
      (adjusted OR=6.37; 95% CI=1.6-24.7); and kneeling or squatting (adjusted OR=4.76;
      95% CI=1.4-15.9). More than half of the respondents reported WRMDs. General
      physical and psychosocial work-related exposures, as well as specific therapy
      tasks, were strongly associated with WRMDs. Larger, longitudinal studies are
      needed to determine the direction of causality.

PMID- 20690881
TI  - The role and effectiveness of computer-assisted learning in physical therapy
      education: a systematic review.
AB  - Physical therapy educators seek teaching methodologies to efficiently educate
      students. The purpose of this article was to perform a systematic review of the
      literature pertaining to the use and effectiveness of computer-assisted learning
      (CAL) in physical therapy education. Criteria were established for article
      selection. Articles related to use included those reporting at least a 30% survey
      response return and a sample of at least 50. Articles regarding effectiveness
      included only randomized control studies related to use in physical therapy and
      physical therapy assistant education. Six articles related to the use and 17
      articles related to the effectiveness were identified. Early published
      investigations were focused in the area of anatomy. The survey studies related to
      use indicated that educators highly valued CAL, but they reported initial use to
      be low due to cost. Expanding software development has resulted in higher
      contemporary use. CAL can effectively convey content material compared to
      traditional methods of instruction. CAL is largely underresearched in the field
      of physical therapy compared to other health professions. Recommendations for
      future research include larger studies, broader representation of the practice
      field, and development of interactive programming.

PMID- 20690882
TI  - Does cellular hydrogen peroxide diffuse or act locally?
AB  - Understanding of redox signaling requires data on the spatiotemporal distribution
      of hydrogen peroxide (H(2)O(2)) within the cell. The fluorescent reporter HyPer
      is a powerful instrument for H(2)O(2) imaging. However, rapid diffusion of HyPer
      throughout the nucleocytoplasmic compartment does not allow visualization of
      H(2)O(2) gradients on the micrometer scale. Here we dramatically improved the
      spatial resolution of H(2)O(2) imaging by applying subcytoplasmic targeting of
      HyPer. The membrane-attached reporters identified "microdomains" of elevated
      H(2)O(2) levels within the cytoplasm of the cells exposed to growth factors. We
      demonstrate that diffusion of H(2)O(2) across the cytoplasm was strongly limited,
      providing evidence that H(2)O(2) acts locally inside cells.

PMID- 20690883
TI  - Interobserver agreement in scoring of dual fluorescein and ICG inflammatory
      angiographic signs for the grading of posterior segment inflammation.
AB  - PURPOSE: To test interobserver agreement in the fluorescein/indocyanine green
      angiography (FA/ICGA) scoring system for uveitis. METHODS: Four observers scored
      32 dual FA/ICGAs. Spearman rank correlation was used to analyze correlation
      between pairs of observers in scores assigned to angiographic signs. Kappa
      statistics were used to test agreement between pairs of observers in comparative
      total FA and ICGA scores. RESULTS: The authors found a significant correlation
      between pairs of observers in scores assigned to all FA signs and all except one
      ICGA sign. The only discordant sign was early stromal vessel hyperfluorescence on
      ICGA. There was a moderate to substantial agreement between pairs of observers in
      comparative FA/ICGA total scores. CONCLUSIONS: The level of agreement between
      uveitis specialists in scoring of dual FA/ICGA indicates that the scoring system
      tested in this study will be useful for clinical studies of uveitis. Increased
      experience with this system may further improve its reproducibility.

PMID- 20690885
TI  - Long-acting atypical injectable antipsychotics in the treatment of schizophrenia:
      safety and tolerability review.
AB  - IMPORTANCE OF THE FIELD: Although atypical antipsychotics have beneficial
      efficacy and tolerance, non-adherence and partial adherence remain in patients
      treated for schizophrenia. Long-acting injectable or depot atypical
      antipsychotics offer better medication adherence and tolerability advantages.
      Currently, two drugs are available for the treatment of schizophrenia,
      risperidone long-acting injectable (RLAI) and olanzapine pamoate (OP). AREAS
      COVERED IN THIS REVIEW: Short- and long-term safety and tolerability data on RLAI
      and OP from January 2006 through September 2009 were reviewed by performing
      Medline and PubMed searches, reviewing abstracts and poster presentations, and
      viewing available material from the FDA and European Medicines Agency. WHAT THE
      READER WILL GAIN: RLAI and OP show good short- and long-term safety when treating
      patients with schizophrenia, with uncommon discontinuation due to adverse
      effects. RLAI and OP data show rare problems with injection site reactions and
      patients exposed to injectable treatments prefer to continue injections.
      Infrequent but serious post-injection delirium sedation syndrome occurred after
      1% of OP injections. Weight gain was generally higher among patients treated with
      OP versus RLAI. TAKE HOME MESSAGE: Healthcare providers, patients and family
      members should be made aware of the safety and benefits of long-acting injectable
      atypical antipsychotics in order to diminish the unnecessary restrictions of
      these therapies for patients with schizophrenia.

PMID- 20690886
TI  - Targeting miRNAs in osteoblast differentiation and bone formation.
AB  - IMPORTANCE OF THE FIELD: Bone tissue arises from mesenchymal stromal cells (MSCs)
      differentiated into the osteoblast lineage by genetic and epigenetic mechanisms.
      Emerging evidence indicates that the class of small non-coding single-stranded
      RNAs known as "microRNAs (miRNAs)" also plays a critical role in this process.
      AREAS COVERED IN THIS REVIEW: In this short review, we summarize the biology and
      functional mechanisms of miRNAs. Importantly, we discuss miRNA expression, miRNA
      function, miRNA target prediction, miRNA overexpression and inhibition methods
      applied in osteoblastogenesis. WHAT THE READER WILL GAIN: We discuss the
      potential therapeutic opportunities and challenges for improving the treatment of
      bone-related diseases by using miRNAs as a therapeutic target. TAKE HOME MESSAGE:
      Although various microRNAs regulate cell proliferation and differentiation, only
      a few miRNAs has been reported so far to play a key role in the regulation of
      osteoblast differentiation and bone formation.

PMID- 20690888
TI  - Emerging drugs for high-grade osteosarcoma.
AB  - IMPORTANCE OF THE FIELD: Osteosarcoma (OS) is the most common primary malignant
      bone tumour in children and adolescents. This review focuses on the most
      promising therapeutic markers and drugs which may potentially be considered for
      innovative high-grade OS treatments. AREAS COVERED IN THIS REVIEW: The list of
      drugs and compounds reviewed has been generated by taking into account those
      which target markers of potential clinical interest for high-grade OS and have
      been included in Phase I, II or III clinical trials. The literature search covers
      the last 40 years, starting from the first OS chemotherapy reports of the early
      1970s. Particular relevance was given to reports and reviews on new targeted
      therapies of possible clinical usefulness for high-grade OS. WHAT THE READER WILL
      GAIN: This review gives an updated overview of novel therapeutic approaches which
      have been or are going to be evaluated in Phase I/II/III clinical studies for
      high-grade OS. TAKE HOME MESSAGE: On the basis of the information that has
      emerged so far, it can be predicted that in the next 5 - 10 years, new agents to
      be included in innovative treatment strategies for selected subgroups of high
      grade OS patients may become available.

PMID- 20690889
TI  - Combinations of inhibitors of the renin-angiotensin system with calcium channel
      blockers for the treatment of hypertension: focus on perindopril/amlodipine.
AB  - BACKGROUND: Combination antihypertensive therapy with an inhibitor of the renin
      angiotensin system (RAS) and a calcium channel blocker (CCB) is a rational
      approach to achieve blood pressure (BP) goals in patients with hypertension, and
      may provide additional cardiovascular protection compared to other strategies in
      special populations. This article reviews the rationale for, and evidence
      supporting, the use of newer fixed-dose combinations of RAS inhibitors and CCBs,
      with particular emphasis on perindopril/amlodipine. METHODS: A literature search
      was performed in Medline and EMBASE databases to identify articles published up
      to May 2010 describing the impact of combination treatment with angiotensin
      receptor blocker (ARB)/CCB or angiotensin-converting enzyme (ACE) inhibitor/CCB
      based antihypertensive strategies on BP or clinical outcomes. FINDINGS: A
      substantial body of evidence supports the BP-lowering efficacy of RAS
      inhibitor/CCB combination therapy in patients with hypertension. RAS inhibitors
      and CCBs represent two different and complementary mechanisms of actions; their
      use in combination is associated with effective BP lowering with favourable
      tolerability and fewer adverse metabolic effects than some other combination
      therapies. Currently, intervention studies demonstrating the impact of ARB/CCB
      combinations on cardiovascular mortality and morbidity are lacking. However,
      evidence from large outcome trials supports the use of ACE inhibitor/CCB
      combinations for reducing the risk of cardiovascular and renal events,
      particularly in high-risk patients. There is also evidence that the benefits of
      ACE inhibitor/CCB combinations may extend beyond those solely associated with
      brachial BP lowering, by an additional impact on central BP haemodynamics.
      CONCLUSIONS: RAS inhibitor/CCB combination therapy is an effective
      antihypertensive therapy. Strong evidence supports the antihypertensive efficacy
      of ACE inhibitor/CCB combinations with cardioprotective and renoprotective
      properties. In particular, evidence suggests that fixed-dose
      perindopril/amlodipine effectively decreases BP and currently is the only RAS
      inhibitor/CCB combination proven to decrease all-cause and cardiovascular
      mortality as well as major cardiovascular events, and thus is a valuable option
      for the management of hypertension, especially in high-risk patients.

PMID- 20690890
TI  - Effects of long-term non-invasive home mechanical ventilation on chronic
      respiratory failure.
AB  - OBJECTIVE: Chronic respiratory failure (CRF) is a syndrome defined by certain
      disturbances in arterial blood gases. Non-invasive mechanical ventilation (NIMV)
      is an increasingly used treatment modality in respiratory failure. The aim of
      this study was to investigate the long-term effects of NIMV on pulmonary function
      and survival of patients with CRF. METHODS: The study enrolled 170 CRF patients
      who it was decided should receive long-term home mechanical ventilation. Patients
      were stratified into two distinct groups - Group I (patients for whom NIMV was
      recommended and who had used it) and Group II (patients for whom NIMV was
      recommended at least 1 year ago but who had not used it for various reasons).
      Best arterial blood gas and pulmonary function test values in the year before the
      NIMV recommendation were obtained from patient records. The same tests were
      performed at least 1 year (1-5 years) after initiation of NIMV therapy in Group I
      patients and at least 1 year (1-5 years) after prescription of the device in
      Group II. RESULTS: In the assessments performed 1 year after NIMV recommendation,
      no difference was found between groups in terms of hospital admissions. However,
      in Group I, intra-group analysis showed a reduction in the number of
      hospitalizations 1 year after NIMV. A marked reduction in PaCO(2) level was found
      in Group I patients 1 year after NIMV therapy. Mean survival after NIMV
      recommendation was 40.27 +/- 3.56 months in Group I, and 27.35 +/- 3.68 months in
      Group II (log rank = 7.79; p = 0.005). It was found that survival time increased
      as duration of NIMV usage increased. CONCLUSION: NIMV therapy has some important
      and significant benefits in patients with hypercapnic chronic respiratory
      failure. This study has some limitations in terms of patient selection, power
      analysis and survival analysis. To assess the effects of NIMV on mortality and
      pulmonary functions, the authors believe that there is need for prospective,
      controlled, multicentre studies with longer follow-up periods, improved adherence
      and novel ventilator modes and settings.

PMID- 20690891
TI  - Cost analysis of flavocoxid compared to naproxen for management of mild to
      moderate OA.
AB  - OBJECTIVE: Flavocoxid is a medical food used for the clinical dietary management
      of osteoarthritis (OA). The acquisition cost of flavocoxid is higher than most
      traditional, generic NSAIDs. However, flavocoxid may have more favorable
      gastrointestinal (GI) toxicity resulting in lower overall costs. These costs have
      not been previously examined. This study provides a decision analytic model to
      assess the net costs of using flavocoxid for OA from a Medicare perspective.
      RESEARCH DESIGN AND METHODS: A decision model was developed to estimate the total
      costs associated with flavocoxid versus naproxen for the management of Medicare
      patients with mild to moderate OA. Probabilities were obtained from literature
      and expert opinion, and costs were obtained from Medicare. Sensitivity analyses
      were conducted by varying probabilities and costs within clinically relevant
      ranges. RESULTS: The base case resulted in flavocoxid having lower total annual
      costs ($1482 per patient) compared to naproxen ($1592). Flavocoxid remained the
      lowest cost option when the cost inputs were varied by 25% (above and below the
      base case), and when the probability of GI events with flavocoxid were varied by
      25%. However, when GI rates from the literature and implied relative risks from
      the expert panel were used, or if the cost of PPIs was $0, then naproxen was the
      less costly alternative, though saving less than the annual cost of flavocoxid.
      Key limitations were the limited outcomes in the model (only GI events), lack of
      consideration of adherence or combination therapy, and the reliance on expert
      opinion due to a lack of data for flavocoxid. CONCLUSIONS: In patients over 65
      years of age who suffer from mild to moderate OA, flavocoxid may result in lower
      overall costs, despite a higher acquisition cost. Managed care organizations
      should consider total health care costs in the decision to include flavocoxid as
      a covered benefit.

PMID- 20690892
TI  - Leptin gene therapy in the fight against diabetes.
AB  - IMPORTANCE OF THE FIELD: The incidence of diabetes is increasing worldwide, yet
      current treatments are not always effective for all patient or disease types.
      AREAS COVERED IN THIS REVIEW: Here, we summarize the biologic and clinical roles
      of leptin in diabetes, and discuss candidate viral vectors that may be employed
      in the clinical use of central leptin gene therapy for diabetes. WHAT THE READER
      WILL GAIN: We discuss how studies on leptin, a regulator of the insulin-glucose
      axis, have significantly advanced our understanding of the roles of energy
      homeostasis and insulin resistance in the pathogeneses of metabolic syndrome and
      diabetes. Recent studies have demonstrated the long-term therapeutic effects of
      central leptin gene therapy in obesity and diabetes via decreased insulin
      resistance and increased glucose metabolism. Many of these studies have employed
      viral vectors, which afford high in vivo gene transduction efficiencies compared
      with non-viral vectors. TAKE HOME MESSAGE: Adeno-associated viral vectors are
      particularly well suited for central leptin gene therapy owing to their low
      toxicity and ability to drive transgene expression for extended periods.

PMID- 20690893
TI  - Canadian cost-effectiveness analysis of solifenacin compared to oxybutynin
      immediate-release in patients with overactive bladder.
AB  - OBJECTIVE: To estimate the cost effectiveness of solifenacin 5 mg/day compared to
      oxybutynin immediate-release (IR) 15 mg/day in patients with overactive bladder,
      from the perspective of the Canadian healthcare (payer) system. RESEARCH DESIGN
      AND METHODS: A Markov model was adapted to estimate the incremental cost per
      quality-adjusted life-year (QALY) of solifenacin and oxybutynin IR over a 1-year
      time horizon, based on efficacy and discontinuation data from the Canadian VECTOR
      (VEsicare in Comparison To Oxybutynin for oveRactive bladder patients) study. In
      the model, patients who discontinued treatment were offered tolterodine extended
      release 4 mg/day as second-line. Model robustness was tested using various
      sensitivity analyses. Utility values were derived from published literature;
      incontinence pads were included in a secondary analysis. RESULTS: In the base
      case analysis, total costs over 1 year were CAN$695 and CAN$550 in the
      solifenacin and oxybutynin IR groups, respectively. When including incontinence
      pad costs, there was an incremental saving of CAN$1,831 per patient with
      solifenacin. Solifenacin was associated with an incremental QALY gain of 0.01
      over 1 year. In the base-case analysis without incontinence pads, the incremental
      cost-utility ratio for solifenacin was CAN$14,092. Probabilistic analyses showed
      no overlap in the 95% confidence intervals for total costs or QALYs with or
      without incontinence pads. Solifenacin was cost effective in >90% of cases, based
      on a willingness-to-pay threshold of CAN$50,000 per additional QALY, irrespective
      of whether pad costs were included in the model. The most influential variables
      were the discontinuation rates and the cost of incontinence pads. Limitations of
      the analysis relate mainly to the fact that data in the VECTOR study were
      collected using a direct questioning approach, which might have increased the
      reporting of dry mouth. CONCLUSIONS: Solifenacin 5 mg/day was a cost-effective
      treatment compared with oxybutynin IR 15 mg/day. TRIAL REGISTRATION: NCT00431041
      (of the VECTOR study, upon which the analysis in this paper was based).

PMID- 20690894
TI  - Extraction and phytochemical investigation of Calotropis procera: effect of plant
      extracts on the activity of diverse muscles.
AB  - CONTEXT: Calotropis procera (Ait.) R.Br. (Asclepiadaceae) is a shrub or small
      tree that grows wild in Egypt. Calotropis acts as a purgative, anthelmintic,
      anticoagulant, palliative (in problems with respiration, blood pressure),
      antipyretic, and analgesic, and induces neuromuscular blocking activity. Little
      research has been done to study the electrophysiological effects of this plant's
      extracts on cardiac, smooth, and skeletal muscle activities. OBJECTIVE: The
      present study was conducted to determine the phytochemical composition and the
      effect of the total alcohol extract of the shoot of the plant, which contains
      almost all of C. procera's cardiac glycosides, flavonoids, and saponins. Also,
      this study attempted to throw more light on the electrophysiological effects of
      the plant extracts on cardiac, smooth, and skeletal muscle activities and to
      clarify the mechanism(s) of their observed action(s). MATERIALS AND METHODS: The
      aerial parts of the plant were air dried and their ethanol extracts partitioned
      with successive solvents. Cardiac, smooth, and skeletal muscles were used in this
      study to investigate the physiological and pharmacological effects of the plant
      extracts from different solvents. The data were analyzed by paired t-test.
      RESULTS: The phytochemical investigation of Calotropis procera revealed the
      presence of cardenolides, flavonoids, and saponins. The effects of ethanol, n
      butanol, and ethyl acetate (EtOAc) extracts were each evaluated on isolated toad
      heart and their mechanisms of action determined. Perfusion with 2 MUg/mL ethanol,
      0.2 MUg/mL butanol, and 0.2 MUg/mL EtOAc extracts caused a significant decrease
      in heart rate (bradycardia), significant increase in the force of ventricular
      contraction, and increase in T-wave amplitude. In addition, the effects of
      different extracts of the studied plant on smooth muscle and skeletal muscle were
      investigated in this study. The different extracts and latex of C. procera
      induced a negative chronotropic effect and decreased the heart rate (HR) of
      isolated toad heart. The different extracts increased the power of contraction of
      the duodenum (trace a). Pretreatment with atropine sulfate as a muscarinic
      receptor blocker abolished the stimulatory effect of the different plant extracts
      and latex of C. procera (trace b). DISCUSSION: The present data suggest that
      ethanol, butanol, and EtOAc extracts of Calotropis procera have negative
      chronotropism and positive inotropism. Verapamil could abolish the inotropic
      effect of ethanol as well as that of butanol and EtOAc extracts. Meanwhile,
      atropine did not abolish the observed negative chronotropic effect. The ethanol
      extract increased the power of contraction of rabbit duodenum, but atropine
      abolished this effect. It also decreased the skeletal muscle contraction; this
      effect could be through blocking of the nicotinic receptors. Butanol and EtOAc
      extract data for smooth and skeletal muscles are very close to those for the
      corresponding ethanol extract of the studied plant. The present data for C.
      procera indicate its direct action on the myocardium, its increase of smooth
      muscle motility, and its relaxation of skeletal muscle contraction. The chemical
      constituents could directly affect the cell membrane probably through receptors
      coupling to G proteins. They regulate the ion channel physiology as in the
      myocardium. CONCLUSION: The present data on the extracts of C. procera indicate a
      direct action on the myocardium, stimulatory effect on smooth muscle motility,
      and relaxant action on skeletal muscle contraction. Chemical constituents could
      directly affect the cell membrane probably through receptors coupling to G
      proteins. They regulate the ion channel physiology as in the myocardium.

PMID- 20690895
TI  - Anti-stress effect of ethyl acetate soluble fraction of Morus alba in chronic
      restraint stress.
AB  - CONTEXT: Restraint stress is a well-known method to induce chronic stress which
      leads to alterations in various behavioral and biochemical parameters. OBJECTIVE:
      The present work was designed to study anti-stress effects of Morus alba in
      chronic restraint stress (RS)-induced perturbations in behavioral, biochemical
      and brain oxidative stress status. MATERIALS AND METHODS: The stress was produced
      by restraining the animals inside an adjustable cylindrical plastic tube for 3 h
      once daily for ten consecutive days. The ethyl acetate soluble fraction of Morus
      alba (EASF) 25, 50, 100 mg/kg and diazepam (1 mg/kg) per day was administered 60
      min prior to the stress procedure. The behavioral and biochemical parameters such
      as open field, cognitive dysfunction; leucocytes count; blood glucose and
      corticosteroid levels were determined. On day 10, the rats were sacrificed and
      biochemical assessment of superoxide dismutase (SOD), lipid peroxidation (LPO),
      catalase (CAT), and glutathione reductase (GSH) in whole rat brain were
      performed. RESULTS: Chronic restraint stress produced cognitive dysfunction,
      altered behavioral parameters, increased leucocytes count, SOD, LPO, glucose and
      corticosterone levels, with concomitant decrease in CAT and GSH activities.
      Gastric ulceration, adrenal gland and spleen weights were also used as the stress
      indices. All these RS induced perturbations were attenuated by EASF of Morus
      alba. DISCUSSION: The results of the study suggest that in addition to its
      classically established pharmacological activities, the plant also has immense
      potential as an anti-stress agent of great therapeutic relevance. CONCLUSION:
      This study indicates the beneficial role of Morus alba for the treatment of
      oxidative stress-induced disorders.

PMID- 20690897
TI  - Membrane interactions of amyloid proteins and peptides.

PMID- 20690896
TI  - In vitro photo-induced cytotoxic activity of Citrus bergamia and C. medica L. cv.
      Diamante peel essential oils and identified active coumarins.
AB  - CONTEXT: The search for innovative therapeutic approaches is gaining more
      interest in clinical oncology. OBJECTIVE: In the present investigation we
      reported the chemical profile and the photo-induced cytotoxic activity of two
      endemic Calabrian Citrus species (Rutaceae): Citrus bergamia Risso & Poit. and
      Citrus medica L. cv. Diamante. MATERIALS AND METHODS: Essential oils were
      obtained by hydrodistillation and analyzed by GC and GC/MS. In order to evaluate
      the cytotoxic activity two melanoma models, such as amelanotic melanoma C32 and
      malignant melanoma A375, were used. RESULTS: The essential oil of C. bergamia was
      characterized by limonene, linalyl acetate, gamma-terpinene, linalool and beta
      pinene as major components. The most abundant compounds of C. medica cv. Diamante
      oil were limonene, gamma-terpinene, citral, geranial, beta-pinene and alpha
      pinene. Two coumarins, bergapten and citropten, were also identified in C.
      bergamia and C. medica cv. Diamante, respectively and tested for biological
      activity. Both C. bergamia and C. medica cv. Diamante oils exhibited a selective
      interesting activity against the A375 cell line with IC(50) values of 79.3 and
      89.1 microg/mL, respectively, after 100 min exposure to UV irradiation. The
      strong antiproliferative activity demonstrated with bergapten (IC(50) value of
      71.3 microg/mL after 20 min of irradiation) was not found with citropten.
      DISCUSSION AND CONCLUSION: Our study suggested that UV irradiation is effective
      in activating essential oils and in particular bergapten. This phototoxicity may
      be considered as a treatment option in some cases of lentigo maligna or lentigo
      maligna melanoma.

PMID- 20690898
TI  - Comparative efflux of saquinavir, ritonavir and lopinavir from primary human
      cells.
AB  - Therapeutic drug monitoring is an important element in the management of drug
      treatment in HIV-1 infected patients. We have examined the effect of temperature
      on the egress of HIV-1 protease inhibitors from primary T lymphocytes to
      determine optimum conditions to be adopted in the processing of blood samples in
      order to accurately estimate intracellular or plasma drug concentrations.
      Peripheral blood mononuclear cells or U937 cells were incubated with
      radiolabelled saquinavir, ritonavir or lopinavir at a concentration of 1 uM. The
      cells were washed and resuspended in RPMI medium (without radiolabelled drug) and
      further incubated at 37 degrees C, room temperature (21 degrees C) or at 4
      degrees C. We observed that release of drug ensued upon the removal of cells from
      bathing media containing drug, with the rate of efflux being slower at 4 degrees
      C and fastest at 37 degrees C for all the protease inhibitors. There was a more
      rapid efflux of saquinavir and ritonavir than lopinavir from both cultured
      monocytic and primary human cells. The rank order of the partition coefficient of
      the drugs were lopinavir > saquinavir > ritonavir. All factors that may limit
      optimal estimation of cell-associated drug concentrations must be considered so
      that intracellular concentrations of drug can be accurately estimated.

PMID- 20690899
TI  - In vitro screening of metabolic clearance using two concentration points.
AB  - For high throughput screens, the quickest methodology possible is desirable, but
      a substantial amount of potentially useful information is lacking since most
      screens for metabolic stability are conducted at one concentration, and sometimes
      at one time point. Information that would benefit projects during the discovery
      phase are to know the metabolic rate linearity (K(m) value) and projected hepatic
      clearance (CL(h) value), which is possible by the addition of one more
      concentration. This study used the FDA-preferred probe cytochrome P450 substrates
      to determine K(m), V(max), and CL(int) values. The results showed that compounds
      with relatively high metabolic rates produced more accurate and reproducible
      results that match well with predicted K(m) values according to the FDA. On the
      other hand, compounds with relatively low metabolic rates yielded more variable
      results. Thus, the use of two substrate concentrations should be useful with
      screening assays for assessing the kinetic values for other compounds.

PMID- 20690900
TI  - Reversible covalent binding of neratinib to human serum albumin in vitro.
AB  - Neratinib (HKI-272), an irreversible inhibitor of Her 2 tyrosine kinase, is
      currently in development as an alternative for first and second line therapy in
      metastatic breast cancer patients who overexpress Her 2. Following incubation of
      [(14)C]neratinib in control human plasma at 37 degrees C for 6 hours, about 60%
      to 70% of the radioactivity was not extractable, due to covalent binding to
      albumin. In this study, factors that could potentially affect the covalent
      binding of neratinib to plasma proteins, specifically to albumin were
      investigated. When [(14)C]neratinib was incubated at 10 MUg/mL in human serum
      albumin (HSA) or control human plasma, the percent binding increased with time;
      the highest percentages of binding (46 and 67%, respectively) were observed at 6
      hours, the longest duration of incubation examined. Binding increased with
      increasing temperature; the highest percentages of binding to HSA or human plasma
      (59 and 78%) were observed at 45 degrees C, the highest temperature tested. The
      binding also increased with increasing pH of incubation; the highest percentages
      of binding (56 and 65%) were observed at pH 8.5, the highest pH value tested. The
      percentages of binding were similar (53% to 57%) when a wide range of
      concentrations of [(14)C]neratinib (50 ng/mL to 10 MUg/mL) were incubated with
      human plasma at 37 degrees C for 6 hours, indicating that the binding was
      independent of the substrate concentration, especially in the therapeutic range
      (50 to 200 ng/mL). When human plasma proteins containing covalently bound
      [(14)C]neratinb were suspended in a 10 fold volume of phosphate buffer at pH 4.0,
      6.0, 7.4, and 8.5, and further incubated at 37 degrees C for ~ 16 hours, about
      45%, 44%, 32%, and 12% of the total radioactivity, respectively, was released as
      unchanged [(14)C]neratinib, indicating that the binding is reversible in nature,
      with more released at pH 7.4 and below. In conclusion, the covalent binding of
      neratinib to serum albumin is pH, time and temperature dependent, but not
      substrate concentration dependent, especially in the therapeutic range.
      Acidification and incubation of human plasma proteins that contained covalently
      bound [(14)C]neratinib leads to the release of the drug, indicating that the
      binding is reversible in nature. It is reasonable to speculate that the release
      of neratinib from human serum albumin provides a transport system leading to
      release of neratinib in the more acidic environment of the tumor.

PMID- 20690901
TI  - Sol gel method performed for biomedical products implementation.
AB  - Sol-gel technology is an impressive and instructive innovation in science that
      necessitates a multidisciplinary approach for its important applications in the
      practice. An important peculiarity of the sol gel technology is the possibility
      to control the mechanism and kinetics of the chemical reactions, thus monitoring
      the final structure (particle size, porosity, thin layer thickness) of the
      materials. The low processing temperature combined with the intrinsic bio
      compatibility and environmental friendliness of the implied components makes it
      an ideal method applied in different biomedical purposes: the synthesis of porous
      matrices for entrapping of organic and inorganic compounds, sensor molecules,
      enzymes and many other biological molecules, selective coatings for optical and
      electrochemical biosensors, stationary phases for chromatography, immunoadsorbent
      and solid-phase extraction materials, controlled release agents, solid-phase
      biosynthesis, and unique matrices for biophysical studies. It is therefore the
      scope of this review to provide a few insights of the recent progresses made in
      sol-gel-based materials for biomedical applications.

PMID- 20690902
TI  - Epidermal growth factor down-regulates the expression of human hepatic stimulator
      substance via CCAAT/enhancer-binding protein beta in HepG2 cells.
AB  - hHSS (human hepatic stimulator substance), acting as a hepatotrophic growth
      factor, promotes liver regeneration. However, the regulatory mechanisms for hHSS
      transcription are still poorly understood. In the present study, we investigated
      transcription of hHSS triggered by EGF (epidermal growth factor) and the role of
      C/EBPbeta (CCAAT/enhancer-binding protein beta) as a potential core factor
      responsible for hHSS transcription in HepG2 cells. The results show that EGF
      suppresses hHSS mRNA expression at early time points. Using a promoter deletion
      assay, we identified a proximal region (-358/-212) that is required for EGF
      suppression. Overexpression of C/EBPbeta enhances EGF suppression of hHSS, and
      mutation of the C/EBPbeta-binding site at -292/-279 or siRNA (short interfering
      RNA) interference abolishes EGF suppression. Furthermore, using an
      electrophoretic mobility-shift assay and chromatin immunoprecipitation analysis,
      we found that C/EBPbeta specifically binds to the -292/-279 site that is
      responsible for EGF inhibition. Moreover, using a knockin (overexpression) and
      knockdown strategy (siRNA), we confirmed that C/EBPbeta is a key factor
      responsible for inhibition of hHSS mRNA expression. Pre-treatment with an
      inhibitor of JNK (c-Jun N-terminal kinase) or down-regulation of JNK1 with
      specific siRNA reverses EGF-inhibited hHSS expression. Our results provide a
      crucial regulatory mechanism for EGF in hHSS transcription within the promoter
      proximal region.

PMID- 20690903
TI  - Transcriptional control of genes involved in ciliogenesis: a first step in making
      cilia.
AB  - Cilia and flagella have essential functions in a wide range of organisms. Cilia
      assembly is dynamic during development and different types of cilia are found in
      multicellular organisms. How this dynamic and specific assembly is regulated
      remains an important question in cilia biology. In metazoans, the regulation of
      the overall expression level of key components necessary for cilia assembly or
      function is an important way to achieve ciliogenesis control. The FOXJ1 (forkhead
      box J1) and RFX (regulatory factor X) family of transcription factors have been
      shown to be important players in controlling ciliary gene expression. They
      fulfill a complementary and synergistic function by regulating specific and
      common target genes. FOXJ1 is essential to allow for the assembly of motile cilia
      in vertebrates through the regulation of genes specific to motile cilia or
      necessary for basal body apical transport, whereas RFX proteins are necessary to
      assemble both primary and motile cilia in metazoans, in particular, by regulating
      genes involved in intraflagellar transport. Recently, different transcription
      factors playing specific roles in cilia biogenesis and physiology have also been
      discovered. All these factors are subject to complex regulation to allow for the
      dynamic and specific regulation of ciliogenesis in metazoans.

PMID- 20690905
TI  - Abstracts of the XXXIX Nordic Congress of Ophthalmology. August 4-7, 2010.
      Reykjavik, Iceland.

PMID- 20690904
TI  - Tackling the pathogenesis of RNA nuclear retention in myotonic dystrophy.
AB  - DM1 (myotonic dystrophy type I) is a common form of muscular dystrophy that
      affects mainly adults. It is a disease that belongs to the group of defective RNA
      export diseases, since a major part of the pathogenic mechanism of the disease is
      the retention of the mutant transcripts in the cell nucleus. The presence of an
      expanded CUG trinucleotide repeat in the 3'-UTR (3'-untranslated region) of the
      DMPK (myotonic dystrophy protein kinase) gene causes the attraction of RNA
      binding proteins by the nuclear-located mutant transcripts. As a result of the
      occupation of the RNA-binding proteins, there is defective mis-splicing of
      several cellular transcripts. This is believed to be a major pathogenic mechanism
      of the disease and any attempt to repair the activities of the RNA-binding
      proteins or target the mutant transcripts should be beneficial for the patients.
      Certain approaches have been described in the literature and they demonstrate
      progress in various directions. The purpose of the present review is to summarize
      the successful attempts to tackle the pathogenesis caused by nuclear retention of
      mutant transcripts in myotonic dystrophy and to discuss the possible gains from
      such approaches.

PMID- 20690906
TI  - Building capacity for rural and remote research.

PMID- 20690907
TI  - Progressing rural and remote health research.

PMID- 20690908
TI  - Pandemic influenza vaccination: will the health care system take its own
      medicine?
AB  - OBJECTIVE: To identify factors associated with acceptance of the pandemic
      Influenza A H1N1 California 7/09 vaccine (pH1N1 vaccine) in rural hospital staff.
      DESIGN: Cross-sectional group administered survey. SETTING: A 58-bed rural
      Queensland hospital, over a 10-day period starting five days after commencement
      of the pH1N1 vaccination program. PARTICIPANTS: Hospital staff and students. MAIN
      OUTCOME MEASURES: Intention to receive pandemic influenza vaccination, seasonal
      influenza vaccination. RESULTS: The survey was completed by 252 staff and
      students (full response rate 76.1%, cooperation rate 98.4%). The majority of
      respondents had already decided whether or not to receive the pH1N1 vaccine: 111
      (44.0%) intended to be vaccinated, 63 (25.0%) intended not to be vaccinated and
      78 (31.0%) were undecided. Of 125 staff who had received the seasonal influenza
      vaccine, 86 (68.8%) intended to receive the pandemic vaccine. Respondents were
      less likely to state acceptance of the pH1N1 vaccine if they identified concern
      about vaccine adverse reactions (odds ratio (OR) 0.29; 95% confidence interval
      (CI), 0.11-0.78), vaccine safety (OR 0.20; 95% CI, 0.09-0.46), vaccine efficacy
      (OR 0.20; 95% CI, 0.04-0.87) or perceived limitations of vaccine trials (OR 0.08;
      95% CI, 0.01-0.99) as primary reasons discouraging pandemic influenza
      vaccination. CONCLUSIONS: There is considerable concern among rural hospital
      staff regarding pH1N1 vaccine adverse reactions, safety, efficacy and the
      adequacy of clinical trials on its use. Education specifically addressing these
      concerns might increase pandemic vaccine acceptability.

PMID- 20690909
TI  - Rural student doctors top city colleagues: representation of a rural clinical
      school in the rural press.
AB  - OBJECTIVE: To describe the way in which the rural press portrays a rural clinical
      school and its staff and students. DESIGN: Textual analysis of a collection of
      newspapers kept by the local campuses of the University of New South Wales Rural
      Clinical School (UNSW RCS). THE STUDY: The UNSW established a RCS in January
      2000. This study sampled a total of 225 articles from eleven rural newspapers, a
      collection held by the campuses of the rural clinical schools. The major themes
      of the articles were identified; the descriptive terms the newspaper articles
      used for medical students, the UNSW RCS and rural doctors were also identified.
      The way in which clinical schools, their staff and students, are portrayed in the
      rural press has the potential to influence recruitment and retention.
      CONCLUSIONS: The study showed that the rural press was strongly supportive of the
      rural clinical school in their local region. This was particularly true for
      medical students, the school itself and the potential impact on workforce. The
      newspapers provided information for future students, depicting work-experience
      programs and current students. They were less illustrative of current medical and
      academic staff, with the exception of the Head of School.

PMID- 20690910
TI  - Short-stay rural and remote placements in dental education, an effective model
      for rural exposure: a review of eight-year experience in Western Australia.
AB  - OBJECTIVES: The increase in demand for dental care over the next 10 years is
      expected to outstrip the supply of dental visits in Australia, resulting in an
      ongoing shortage of dental practitioners. As trends in medicine have shown, the
      greatest effect will be felt in rural and remote regions, where an undersupply of
      dentists already exists. It is clearly evident that it is important to provide
      strategies that will increase the recruitment and retention of practitioners in
      rural and remote areas. Previous research suggested an increased likelihood for
      health graduates to choose rural practice if they have a rural background, or
      were exposed to rural practice during their education. Short-stay (three to four
      weeks) placements for final-year dental students has been part of dental
      education in Western Australia for near on a decade. METHODS: This paper reflects
      on the experiences gained from managing this placement program. CONCLUSIONS:
      Short-stay placements are a quality learning initiative but need a high level of
      planning and a clear vision to be effective. IMPLICATIONS: The key factors in
      ensuring sustainable, student centred learning is driven through a small core
      group of staff who have strong direct links with rural and remote communities,
      students and support providers. The integration of service, education and
      research goals have played a critical role in sustaining placements. The
      philosophy underpinning the rural placements needs to be clearly articulated and
      applied effectively in each step of their implementation and a highly focused
      customer-service driven implementation is required to make short-stay rural and
      remote placements effective.

PMID- 20690911
TI  - Changes in depression-related mental health literacy in young men from rural and
      urban South Australia.
AB  - OBJECTIVE: To examine rural and urban differences in depression-related mental
      health literacy, experience of depression and help-seeking. DESIGN: Cross
      sectional population-based survey stratified by rural and urban area. SETTING: A
      random and representative sample of South Australian rural and urban young men
      aged between 15 and 30 years. OUTCOME MEASURES: Mental health literacy as
      determined by recognition and exposure to classical symptoms of depression;
      perceived helpfulness of various interventions and treatment-seeking behaviour.
      RESULTS: Recognition of depression increased significantly in rural and urban
      young men between 1998 and 2008. More rural young men than urban men identified
      symptoms of depression in 1998 (odds ratio (OR): 1.53, 95% confidence interval
      (CI), 1.01-2.40, P < 0.05), but that was not evident in 2008 (OR: 1.32, 95% CI,
      0.80-2.25, P = 0.30). Both groups were more likely to have a close friend
      experience symptoms of depression and to use antidepressant medications in 2008
      compared with 1998. Rural young men experienced a significant increase in
      recognition of personal depressive symptoms (OR: 3.73, 95% CI, 1.72-8.40) and
      levels of confidence in psychiatrists and psychologists (OR: 2.40, 95% CI, 1.34
      4.31) in 2008 compared with 1998. Both rural and urban young men were
      significantly less likely to rate dealing with problems on their own as helpful
      in 2008 as in 1998. CONCLUSIONS: There has been an increase in both rural and
      urban young male mental health literacy between 1998 and 2008, especially in
      rural young men. Whether this will translate into a reduction of depression and
      associated suicide, with a reversal of the rural/urban suicide differential,
      remains to be seen.

PMID- 20690912
TI  - Genital chlamydia in southern New South Wales: an ecological analysis of testing
      and notification patterns 2004-2008.
AB  - OBJECTIVE: To identify demographic patterns for chlamydia testing rates on
      reported general practice (GP) visits and notification rates in residents of
      Greater Southern Area Health Service (GSAHS) for the period 2004-2008. DESIGN:
      Descriptive analysis of presentation and chlamydia-specific Medicare data and
      chlamydia notifications made to GSAHS Public Health Unit. SETTING: Rural and
      remote southern New South Wales. PARTICIPANTS: Residents of GSAHS who had a
      Medicare recorded visit to a GP and chlamydia pathology collected in the period
      July 2004 to June 2008, and those residents notified to the GSAHS Public Health
      Unit with a positive chlamydia test results. MAIN OUTCOME MEASURES: Age and
      gender trends for GP visits, chlamydia testing and chlamydia notifications.
      RESULTS: While chlamydia testing and notification rates increased over the review
      period, the percentage of chlamydia tests performed remained low. There was a
      greater increase in testing rates among women than men, and the highest were
      among women aged 15-24. Chlamydia notification rates increased across all age
      groups and were greater in women aged 15-24 than men of the same age group.
      CONCLUSION: The low proportion of tests performed to presentations (in
      conjunction with the high proportion of notifications to tests performed)
      reflects that chlamydia testing among providers is still being undertaken in a
      targeted approach rather than from a population-focused screening perspective.
      Further work with GPs is required to improve chlamydia screening rates, and
      ensure practice is consistent with national guidelines.

PMID- 20690913
TI  - Evaluating the impact of sustainable comprehensive primary health care on rural
      health.
AB  - OBJECTIVE: To develop a conceptual framework for monitoring the relationship
      between health services and health outcomes in rural Australia. DESIGN AND
      SETTING: Development of an evaluation framework for a rural comprehensive primary
      health service in Victoria. RESULTS: Evidence regarding essential components for
      successful primary health care, and objective health service and health status
      measures were combined to develop a conceptual health service evaluation
      framework. Application of the framework is illustrated using a case study of a
      rural primary health service in Victoria. CONCLUSIONS: Inadequate health services
      limit access to health care, delay use at times of need and result in poor health
      outcomes. Currently, there is a lack of evidence from rigorous health service
      evaluations to indicate which rural health services work well, where and why that
      could inform rural health policies and funding. Although the nature of health
      service models will vary across communities in order to meet their differing
      geographic circumstances, there is considerable scope for the translation and
      generalisation of evidence gained from health service models that are shown to be
      sustainable, responsive and able to deliver local quality health care. This
      framework can guide future health service evaluation research and thereby provide
      a better understanding of a health service's impact on the health of the
      community and its residents.

PMID- 20690914
TI  - Caring of ST-elevation myocardial infarction patients in rural community hospital
      settings: determinants of in-hospital mortality.
AB  - OBJECTIVE: Cardiovascular disease contributes more than three quarters of all
      cardiovascular deaths worldwide. Adherence to myocardial infarction (MI)
      guidelines might not be possible in many rural hospitals. We aim to share our
      three-year experience in rural settings regarding to ST-elevation MI (STEMI)
      patients particularly by focusing on determinants of in-hospital mortality.
      METHODS: We retrospectively analysed our data for 559 acute STEMI patients
      admitted to our coronary care unit in Kastamonu city, Turkey between August 2004
      and August 2007. Key demographic and clinical characteristics and data regarding
      symptom duration, prehospital transfer settings and insurance status were
      collected. Killip classes and in-hospital therapy of all patients were recorded.
      RESULTS: A total of 54 patients (9.66%) died within the hospitalisation period.
      Multivariate analysis revealed that advanced age > 65 years, late admission,
      hypotension at presentation, killip class > 2, anterior location, posterior
      location, lack of fibrinolysis and cardiogenic shock were independent predictors
      of in-hospital mortality. CONCLUSIONS: In rural hospital settings, clinical
      resources and transfer facilities are limited. Therefore, improvement of early
      transfer and prehospital fibrinolysis capabilities should decrease mortality.

PMID- 20690915
TI  - International perspectives on the baby trade.

PMID- 20690916
TI  - Reproductive tourism and the quest for global gender justice.
AB  - Reproductive tourism is a manifestation of a larger, more inclusive trend toward
      globalization of capitalist cultural and material economies. This paper discusses
      the development of cross-border assisted reproduction within the globalized
      economy, transnational and local structural processes that influence the trade,
      social relations intersecting it, and implications for the healthcare systems
      affected. I focus on prevailing gender structures embedded in the cross-border
      trade and their intersection with other social and economic structures that
      reflect and impact globalization. I apply a social connection model of
      responsibility for unjust outcomes and consider strategies to counter structural
      injustices embedded in this industry. The concluding section discusses policy
      reforms and proposals for collaborative action to preclude further injustices and
      extend full human rights to all.

PMID- 20690917
TI  - Care ethics and the global practice of commercial surrogacy.
AB  - This essay will focus on the moral issues relating to surrogacy in the global
      context, and will critique the liberal arguments that have been offered in
      support of it. Liberal arguments hold sway concerning reproductive arrangements
      made between commissioning couples from wealthy nations and the surrogates from
      socioeconomically weak backgrounds that they hire to do their reproductive labor.
      My argument in this paper is motivated by a concern for controlling harms by
      putting the practice of globalized commercial surrogacy into the context of care
      ethics. As I will argue, the unstable situations into which children of global
      surrogacy arrangements are born is symbolic of the crisis of care that the
      practice raises. Using the Baby Manji case as my touch point, I will suggest that
      liberalism cannot address the harms experienced by Manji and children like her
      who are created through the global practice of assisted reproductive technology.
      I will argue that, if commissioning couples consider their proposed surrogacy
      contracts from a care ethics point of view, they will begin to think relationally
      about their actions, considering the practice from an ethical lens, not just an
      economic or contractual one.

PMID- 20690918
TI  - Revisiting child-based objections to commercial surrogacy.
AB  - Many critics of commercial surrogate motherhood argue that it violates the rights
      of children. In this paper, I respond to several versions of this objection. The
      most common version claims that surrogacy involves child-selling. I argue that
      while proponents of surrogacy have generally failed to provide an adequate
      response to this objection, it can be overcome. After showing that the two most
      prominent arguments for the child-selling objection fail, I explain how the
      commissioning couple can acquire parental rights by paying the surrogate only for
      her reproductive labor. My explanation appeals to the idea that parental rights
      are acquired by those who have claims over the reproductive labor that produces
      the child, not necessarily by those who actually perform the labor. This account
      clarifies how commercial surrogacy differs from commercial adoption. In the final
      section of the paper, I consider and reject three further child-based objections
      to commercial surrogacy: that it establishes a market in children's attributes,
      that it requires courts to stray from the best interests standard in determining
      custodial rights, and that it requires the surrogate to neglect her parental
      responsibilities. Since each of these objections fails, children's rights
      probably do not pose an obstacle to the acceptability of commercial surrogacy
      arrangements.

PMID- 20690919
TI  - The ethics of intercountry adoption: why it matters to healthcare providers and
      bioethicists.
AB  - The goal of this paper is both modest and ambitious. The modest goal is to show
      that intercountry adoption should be considered by ethicists and healthcare
      providers. The more ambitious goal is to introduce the many ethical issues that
      intercountry adoption raises. Intercountry adoption is an alternative to medical,
      assisted reproduction option such as in vitro fertilization (IVF),
      intracytoplasmic sperm injection, third party egg and sperm donation and
      surrogacy. Health care providers working with assisted reproduction are in a
      unique position to introduce their clients to intercountry adoption; however,
      providers should only do so if intercountry adoption is ethically equal or
      superior to the alternatives. This paper first presents a brief history of
      intercountry adoption. The second section compares intercountry adoption with
      medical alternatives. The third section examines the unique ethical challenges
      that are not shared by other medical alternatives. The final section concludes
      that it is simplistic for a healthcare provider to promote intercountry adoption
      unconditionally; however, in situation where intercountry adoption is practiced
      conscientiously it poses no greater ethical concern than several medical
      alternatives. This conclusion is preliminary and is intended as a start for
      further discussion.

PMID- 20690920
TI  - The limits of intimate citizenship: reproduction of difference in Flemish
      Ethiopian 'adoption cultures'.
AB  - The concept of 'intimate citizenship' stresses the right of people to choose how
      they organize their personal lives and claim identities. Support and interest
      groups are seen as playing an important role in the pursuit of recognition for
      these intimate choices, by elaborating visible and positive cultures that invade
      broader public spheres. Most studies on intimate citizenship take into
      consideration the exclusions these groups encounter when negotiating their
      differences with society at large. However, much less attention is paid to the
      ways in which these groups internalize the surrounding ideologies, identity
      categories and hierarchies that pervade society and constrain their recognition
      as full citizens. In contrast, this paper aims to emphasize the reproduction of
      otherness within alternative spheres of life, and to reveal the ambiguities and
      complexities involved in their dialectic relationship with society at large. To
      address this issue, the paper focuses on the role that 'adoption cultures' of
      Flemish adoptive parents with children from Ethiopia play in the pursuit of being
      recognized as 'proper' families and full citizens. The ethnographic research
      among adoptive parents and adoption professionals shows a defensive discourse and
      action that aims at empowering against potential problems, as well as a tendency
      to other the adoptive child by pathologizing its non-normativity. By showing the
      strong embeddedness of adoptive families' practices of familial and cultural
      construction in larger cultural frames of selfing and othering, characterized by
      biologism and nativism, one begins to understand the limits of their capacity to
      realize full citizenship.

PMID- 20690921
TI  - Should international adoption be part of humanitarian aid efforts? Lessons from
      Haiti.

PMID- 20690923
TI  - Mycoplasma pneumoniae Mpn133 is a cytotoxic nuclease with a glutamic acid-,
      lysine- and serine-rich region essential for binding and internalization but not
      enzymatic activity.
AB  - We identified Mpn133 as a Ca(2+)-dependent cytotoxic nuclease of Mycoplasma
      pneumoniae. Flow cytometry analysis and immunofluorescence studies revealed the
      binding and internalization of recombinant Mpn133 (rMpn133) in human airway A549
      cells. Amino acid sequence comparisons of Mpn133 with other mycoplasma nucleases
      demonstrated the presence of a unique glutamic acid-, lysine- and serine-rich
      region (EKS region; amino acids 72-110). Deletion of this EKS peptide
      (rMpn133(Delta72-110)) abrogated its binding and internalization but not its
      nuclease activity. The function of the EKS region in host cell trafficking and
      nuclear localization was reinforced by the successful delivery of EKS-conjugated
      mCherry protein into A549 cells. rMpn133, but not rMpn133(Delta72-110), induced
      apoptosis-like death in A549 cells. This observation suggested a unique role of
      Mpn133 as an important contributor to M. pneumoniae-associated life cycle events
      and as a virulence factor in host-associated cytopathologies. In addition, the
      distinct property of the EKS peptide in delivery of proteins, like mCherry, into
      target cells opens new avenues to the establishment of novel concepts of drug
      delivery and therapy.

PMID- 20690924
TI  - Clostridium botulinum C2 toxin is internalized by clathrin- and Rho-dependent
      mechanisms.
AB  - Clostridium botulinum C2 toxin is an ADP-ribosyltransferase, causing
      depolymerization of the actin cytoskeleton in eukaryotic cells. The C2 toxin is a
      binary toxin consisting of the enzymatic subunit C2I and the binding subunit
      C2II. Proteolytical activation of the binding subunit triggers the formation of
      heptameric structures (C2IIa), which bind to cellular receptors. C2I is able to
      bind to C2IIa oligomers, and it has been suggested that the whole complex is
      internalized by a raft-dependent mechanism. Here we analysed by which mechanism
      C2 toxin is endocytosed. In HeLa cells expressing a dominant-negative dynamin
      mutant, cytotoxicity and C2 toxin uptake were blocked. Furthermore, siRNA
      mediated knockdown of flotillins or inhibition of Arf6 function, proteins
      suggested to be involved in dynamin-independent endocytosis, did not affect C2
      toxicity. Knockdown of caveolin did not inhibit endocytosis of C2 toxin, whereas
      inhibition of clathrin function reduced the uptake of C2 toxin and delayed the
      cytotoxic effect. Finally, we found evidence for a Rho-mediated uptake of C2
      toxin. In conclusion, C2 toxin is endocytosed by dynamin-dependent mechanisms and
      we provide evidence for involvement of clathrin and Rho.

PMID- 20690932
TI  - A transition scoring system of caries increment with adjustment of reversals in
      longitudinal study: evaluation using primary tooth surface data.
AB  - OBJECTIVES: The aim of this paper is to evaluate a new comprehensive scoring
      system for longitudinal studies using the International Caries Detection and
      Assessment System (ICDAS). METHODS: A sample of 638 children were examined in
      2002-2003 and again in 2007. Caries was assessed using the ICDAS criteria which
      assess six clinical stages of dental caries. Based on a transition matrix
      matching the baseline and follow-up ICDAS scores, we developed transition weights
      to best describe the progression, regression, or no progression nor regression of
      dental caries. Differential weights were assigned to transitions involved with
      noncavitated, cavitated, filled, crowned, or missing lesions. This method
      [transitional scoring system (TSS)] differentiated biologically plausible
      reversals from those because of examiner's misclassification. We computed and
      compared mean dmfs (decayed, missing, and filled tooth surfaces) increment scores
      including (d(t) mfs) or excluding the noncavitated stage (d(c) mfs) from TSS and
      another adjustment method proposed by Beck (modified Beck's method). The
      coefficients of variation (CV) of the two methods were also compared. RESULTS:
      Mean d(t) mfs from TSS was slightly higher than that from modified Beck's method.
      There was no difference in mean d(c) mfs between two methods. The ratios of CV
      indicated that the CV of TSS was significantly smaller than those from modified
      Beck's method. CONCLUSIONS: There were differences in caries increment scores
      between the two methods when we accounted for the transition of noncavitated
      lesions. The evaluation of CV concluded that TSS was more efficient because it
      requires less sample size compared with the modified Beck's method to detect a
      treatment effect. Both methods can be used to compute caries increments for
      populations with similar distribution of the dmfs scores to the sample used in
      this study.

PMID- 20690933
TI  - Tooth loss--an assessment of dental health state utility values.
AB  - OBJECTIVE: The study described aimed to measure the value placed on oral health,
      by measuring the utility of mouths in which teeth had been lost. METHODS: A total
      of 102 subjects who had experienced tooth loss were interviewed and presented
      with 19 different scenarios of mouths with missing teeth. Each written
      description was accompanied by a verbal explanation and digital pictures of mouth
      models. Participants were asked to indicate on a standardized visual analogue
      scale how they would value the health of their mouth if they had lost the
      tooth/teeth described and the resulting space was left unrestored. RESULTS: With
      a utility value of 0.0 representing the worst possible health state for a mouth
      and 1.0 representing the best, the mouth with the upper central incisor missing
      attracted the lowest utility value (utility = 0.16), the one with a missing upper
      second molar and the missing lower second molar attracted the highest utility
      values (utility = 0.48, 0.47, respectively). With respect to shortened dental
      arch (SDA) scenarios, a mouth with a SDA with only the second molar teeth in all
      quadrants missing attracted the highest utility value (utility = 0.45). A mouth
      with an extreme SDA with both missing molar and premolar teeth attracted the
      lowest utility value (utility = 0.06). Both age and gender have a significant
      influence on how the dentition is valued. CONCLUSION: It is feasible and possible
      to derive measurements of the impact of various degrees of tooth loss on
      individuals. Further studies are required to examine whether past tooth loss or
      oral health status affects how tooth loss is viewed.

PMID- 20690934
TI  - Prevalence of dental erosion in children: a national survey.
AB  - OBJECTIVES: To measure the prevalence of dental erosion in permanent teeth in
      Iceland as part of the National Oral Health Survey. METHODS: A representative,
      nationwide sample of 2251 Icelandic children, 20% of those aged 6, 12 and 15
      year, was examined. Dental erosion was recorded for all erupted permanent teeth
      and graded using the modified scale of Lussi. RESULTS: Erosion was not seen in
      the permanent teeth of six-year-olds, but was present in 15.7% of 12-year-olds,
      more frequently in boys than girls (19.9% boys, 11.0% girls; P < 0.001). Among 15
      year-olds, dental erosion was seen among 30.7% of subjects (38.3% boys, 22.7%
      girls; P < 0.001). Severity of erosion was mostly scored as grade I, with only
      5.5% of 15-year-olds scored as grade II, mostly on tooth 46 (4.3%) and 36 (4.2%).
      For 12-year-olds, 0.9% had erosion scores of grade II mostly on tooth 46 (0.8%)
      and 36 (0.7%). No subjects had erosion of grade III. The most common clinical
      manifestation of erosion was the appearance of cup-like lesions on the cusps of
      lower first molars. CONCLUSIONS: Dental erosion was frequently present by the age
      of 12; the prevalence doubled by age 15 and was seen almost twice as often among
      boys than girls. Teeth most frequently showing signs of erosion were the lower
      first molars. The rapidly growing prevalence of erosion demonstrated by this
      nationwide survey emphasizes the need for further research into the aetiology of
      erosion and possible methods of preventing and treating this emerging dental
      problem.

PMID- 20690935
TI  - Attitudes towards oral health among parents of 6-year-old children at risk of
      developing caries.
AB  - OBJECTIVES: Parental attitudes are likely to play a role in achieving and
      maintaining a desired level of oral health in children. To be useful in
      individually delivered caries prevention programmes, parental attitudes should be
      identified at individual level. Q-methodology has been proved successful in
      identifying attitudes in a wide range of disciplines but in dentistry Q-studies
      are scarce. In this study Q-methodology was used to identify parents' prevailing
      attitudes towards the oral health of their children. METHODS:  Thirty-nine
      parents ranked 37 statements regarding the dental health behaviour they apply to
      their 6-year-old child. They later explained their rankings during a short
      interview. In Q-methodology, rather than reporting one average composite attitude
      and opinion, various combinations of opinions and attitudes concerning these
      statements are identified using by-person factor analysis. RESULTS: Based on
      their beliefs, attitudes and cognitions, five categories of parents were found:
      (i) conscious and responsible, (ii) trivializing and fatalistic, (iii) appearance
      driven and open-minded, (iv) knowledgeable but defensive and (v) conscious and
      concerned. CONCLUSIONS:  Q-methodology appears to be a fruitful way to structure
      the complexity of parents' opinions and attitudes towards their children's dental
      health. It appears that Q-methodology provides comprehensive clusters of
      individual attitudes, based on various levels of responses to a wide range of
      questions. The five identified profiles may be useful in developing tailor-made
      prevention strategies in caries prevention.

PMID- 20690936
TI  - Patch testing and contact allergens in Ethiopia--results of 514 contact
      dermatitis patients using the European baseline series.
AB  - BACKGROUND: Patch testing is essential to diagnose allergic contact dermatitis.
      Dermatologists in many countries use a baseline (standard) series covering the
      major allergens responsible for allergic contact dermatitis in their population,
      with the addition of relevant allergens for the individual patient. However, a
      baseline series has not yet been developed for Ethiopia. Our objective in this
      study is to identify common contact allergens to form the basis of a future
      baseline series in Ethiopia. METHODOLOGY: We patch tested 514 subjects with
      dermatitis according to the recommended procedure using the European baseline
      series for 1 year. RESULTS: 52.7% of the tested subjects showed positive reaction
      for at least one allergen tested. The top five contact allergens identified were
      nickel sulfate, fragrance mix I, cobalt chloride, p-tert-butylphenolformaldehyde
      (PTBP) resin and potassium dichromate. Positive reactions to nickel and PTBP were
      commoner in females. PTBP positivity was strongly associated with foot eczema.
      Positive test reactions were commoner in cement workers, notably to potassium
      dichromate, which was also a commoner allergen in patients presenting with hand
      dermatitis. There were no reactions to several allergens, including neomycin,
      benzocaine, budesonide, primin and quaternium-15. CONCLUSION: Comparable patch
      test results with other countries have been shown and the European baseline
      series can be used as a baseline series in Ethiopia with some modification.

PMID- 20690937
TI  - Patch test reactivity to feverfew-containing creams in feverfew-allergic
      patients.
AB  - BACKGROUND: The Compositae plant feverfew (Tanacetum parthenium) has long been
      recognized as an important sensitizer in European Compositae-allergic patients,
      mainly because of its content of the sesquiterpene lactone parthenolide.
      Recently, a parthenolide-depleted feverfew extract with claimed anti-inflammatory
      properties has been developed for use in cosmetics. OBJECTIVE: The aim of the
      study was to test, on the basis of patch test reactions, whether persons with
      contact allergy to feverfew could tolerate creams containing this feverfew
      extract. PATIENTS/MATERIALS/METHODS: Seven patients with feverfew contact allergy
      were patch tested with two creams containing the feverfew extract. Subsequently,
      the creams were analysed by liquid chromatography with tandem mass spectrometry
      to detect parthenolide. RESULTS: Four of the patients tested positive to one of
      the creams; reactivity was associated with simultaneous positive reactions to
      parthenolide. This cream was analysed about 2 years later, and no parthenolide
      was detected, probably because of degradation of the compound. CONCLUSIONS:
      Topical products containing parthenolide-depleted feverfew extracts may elicit
      positive patch test reactions in feverfew-sensitive patients. The reactivity may
      be enhanced by simultaneous testing with parthenolide, but the reactivity is lost
      over time, probably because of degradation of parthenolide.

PMID- 20690938
TI  - Identification of metallic items that caused nickel dermatitis in Danish
      patients.
AB  - INTRODUCTION: Nickel allergy is prevalent as assessed by epidemiological studies.
      OBJECTIVES: In an attempt to further identify and characterize sources that may
      result in nickel allergy and dermatitis, we analysed items identified by nickel
      allergic dermatitis patients as causative of nickel dermatitis by using the
      dimethylglyoxime (DMG) test. MATERIALS AND METHODS: Dermatitis patients with
      nickel allergy of current relevance were identified over a 2-year period in a
      tertiary referral patch test centre. When possible, their work tools and personal
      items were examined with the DMG test. RESULTS: Among 95 nickel-allergic
      dermatitis patients, 70 (73.7%) had metallic items investigated for nickel
      release. A total of 151 items were investigated, and 66 (43.7%) gave positive DMG
      test reactions. Objects were nearly all purchased or acquired after the
      introduction of the EU Nickel Directive. Only one object had been inherited, and
      only two objects had been purchased outside of Denmark. CONCLUSIONS: DMG testing
      is valuable as a screening test for nickel release and should be used to identify
      relevant exposures in nickel-allergic patients. Mainly consumer items, but also
      work tools used in an occupational setting, released nickel in dermatitis
      patients. This study confirmed 'risk items' from previous studies, including
      mobile phones.

PMID- 20690939
TI  - Sensitization to contact allergens and bronchial hyper-responsiveness.
AB  - BACKGROUND: Exposure to contact allergens and specific allergic sensitization to
      them are common, but possible related health effects have been rarely studied.
      OBJECTIVES: We aimed to analyse possible associations between contact
      sensitization to nickel sulfate and fragrance mix I and lung function parameters
      or bronchial hyper-responsiveness. METHODS: Within a population-based study in
      Augsburg, 1052 adults performed lung function tests, including forced expiratory
      volume in 1 second (FEV(1)), forced vital capacity (FVC) and bronchial hyper
      responsiveness (BHR). Patch tests were performed, and information was assessed by
      medical examinations and interviews. Logistic regression models were applied to
      study associations between contact allergies and lung function parameters.
      RESULTS: Women were sensitized significantly more often than men to nickel [odds
      ratio (OR) 3.97, 95% confidence interval (CI) 2.50-6.29] and fragrance mix I (OR
      2.28, 95% CI 1.50-3.46). Patch test results for nickel and fragrance mix I did
      not influence mean FEV(1) and FVC % predicted values. However, in women, a higher
      rate of BHR was associated with positive patch test reactions to fragrance mix I
      (OR 2.24, 95% CI 1.11-4.52). CONCLUSIONS: Contact sensitization to fragrance mix
      I is associated with a higher rate of BHR in women. Thus, in women with contact
      allergy to fragrances, airway obstruction should be considered as a possible co
      morbidity.

PMID- 20690940
TI  - Prevalence and cause of methylisothiazolinone contact allergy.
AB  - BACKGROUND: Methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) has been
      one of the most frequent sensitizers since the 1980s. In 2005, the use of MI
      alone was approved for the preservation of cosmetic and household products in the
      EU. Before that, MI was used in industrial products, and the first cases of
      isolated MI contact allergy were published. OBJECTIVES: To present the prevalence
      and causes of MI contact allergy. MATERIALS AND METHODS: Patch test results from
      2536 dermatitis patients tested with MI at Gentofte University Hospital between
      May 2006 and February 2010 were analysed. A retrospective investigation of
      medical records from MI-allergic patients was performed to reveal the causes of
      their MI contact allergy. RESULTS: Of patch-tested patients, 1.5% had MI contact
      allergy. It was associated with occupational dermatitis, hand eczema and age
      above 40 years. Exposure to MI in cosmetic products was found in 12 (32%) cases,
      and exposure to MI in occupational products was found in 11 (30%) cases; 5 of the
      11 were painters. CONCLUSIONS: The prevalence of MI contact allergy is already at
      the same level as that of other sensitizing preservatives, which have been on the
      market for several years, but no rising trend was identified. MI contact allergy
      was associated with both occupational and consumer products.

PMID- 20690941
TI  - Differential diagnosis of mechanic's hands: think of Jo-1 syndrome.

PMID- 20690942
TI  - Sensitizing oat extracts in cosmetic creams: is there an alternative?

PMID- 20690943
TI  - Allergic contact dermatitis to Elidel cream itself?

PMID- 20690944
TI  - Consort allergic contact dermatitis caused by ketoprofen in a tango dancer.

PMID- 20690945
TI  - How to test for contact allergy in patients with fragile skin.

PMID- 20690946
TI  - The "brain-free" practice.

PMID- 20690947
TI  - Dentin/enamel bonding.

PMID- 20690948
TI  - The role of complete overdentures in esthetic rehabilitation of the adolescent
      oligodontia patient. A case report.
AB  - STATEMENT OF THE PROBLEM: Dental agenesis is a common developmental anomaly among
      human populations. It presents with varying degrees of severity. Oligodontia
      present in the permanent dentition may have significant esthetic, psychosocial,
      as well as functional implications. CASE PRESENTATION: A case of oligodontia in
      an adolescent patient treated with conventional overdentures is presented in this
      article. A thorough medical and dental history were taken. Comprehensive clinical
      and radiographic examinations were made. Diagnostic casts were mounted. The
      prosthetic denture teeth were set and followed by esthetic and phonetic
      evaluation. Following approval by the patient, the overdentures were processed in
      heat cure resin using the conventional techniques. RESULTS: Good esthetic results
      were achieved. Patient was satisfied with the final prostheses. CONCLUSION:
      Simple prosthodontic solutions can be utilized to aid patients with dental
      agenesis. These have great implications for the patient's self image. CLINICAL
      SIGNIFICANCE: Oligodontias are common. The literature frequently addresses
      esthetic rehabilitation using fixed prostheses and dental implants. This case
      report illustrates the value of removable prosthodontic procedures as one
      approach to fulfilling the requirements of esthetic rehabilitation of a young
      oligodontia patient.

PMID- 20690949
TI  - COMMENTARY. The role of complete overdentures in esthetic rehabilitation of the
      adolescent oligodontia patient. A case report.

PMID- 20690950
TI  - Immediate loading of the maxilla with prefabricated interim prosthesis using
      interactive planning software, and CAD/CAM rehabilitation with definitive
      zirconia prosthesis: 2-year clinical follow-up.
AB  - Immediate loading in implant dentistry has provided several advantages for both
      patients and clinicians. Recent advances in computer-aided design/computer-aided
      manufacturing (CAD/CAM) technology, medical imaging and rapid prototyping have
      added to the armamentarium of implant dentistry in terms of efficiency, accuracy
      and predictability. Rapid prototyping and CAD/CAM technology are used to
      fabricate stereolithographic surgical templates for flapless implant placement.
      In addition to that, this technology is also used for the fabrication of zirconia
      frameworks. The zirconia-based implant restorations are gaining popularity in
      implant prosthodontics combining esthetic properties with strength and
      biocompatibility. The purpose of this article is to illustrate the steps for
      implant rehabilitation of the edentulous maxilla with zirconia prosthesis and
      report the 2-year clinical follow-up of novel technological advances in surgical
      placement, provisionalization and fabrication of a definitive restoration.
      CLINICAL SIGNIFICANCE: A comprehensive approach to full mouth implant
      rehabilitation using cutting edge technology is illustrated in a simplified
      manner.

PMID- 20690951
TI  - COMMENTARY. Immediate loading of the maxilla with prefabricated interim
      prosthesis using interactive planning software, and CAD/CAM rehabilitation with
      definitive zirconia prosthesis: 2-year clinical follow-up.

PMID- 20690952
TI  - Radiographical evaluation of the gap at the implant-abutment interface.
AB  - INTRODUCTION: The detection of marginal gaps at the implant-abutment interface is
      a common clinical task in prosthodontic treatment. For the detection of the gap
      intraorally, especially under thick soft tissues the most common method is dental
      radiography. OBJECTIVE: The objective of this experimental study was to
      investigate the accuracy of conservative dental radiography to detect marginal
      gaps at the implant-abutment interface. For these reasons radiographs were taken
      on internal and external hex implants with different experimental gaps and
      inclinations. MATERIALS AND METHODS: The abutment (with a space created by
      plastic sheets 0.5 and 0.2 mm in thickness) was screwed on the implant, and the
      implant was placed into a box filled with silicone impression material. The X-ray
      film was placed parallel to the implant at the back of the box, the borders of
      the box were marked to the base and the box. A ruler of 10 cm was fixed at a long
      X-ray tube to ensure parallelism to the implant, X-ray film. Sets of radiographs
      were made at 0 degrees, 5 degrees, 10 degrees, 15 degrees, 20 degrees, 25
      degrees, 30 degrees (to the abutment) and -5 degrees, -10 degrees, -15 degrees, 
      20 degrees, -25 degrees, -30 degrees (to the implant) degrees. The X-ray images
      were observed with visual examination, under magnification, and in higher
      magnification in a slide projector. The phenomenal and the true gap at the
      implant-abutment interface were calculated in order to determine the distortion.
      RESULTS: There were significant differences between the internal and external hex
      implants because of the different morphology of the implants. The detecting
      ability to diagnose a gap at the implant-abutment interface varied significantly
      with the angulation degree of the X-ray tube. At inclinations to the implant (-
      inclination) the gap diminished earlier than those inclinations to the prosthetic
      abutment (+ inclinations). In all examinations the gap was not detectable at
      angulations higher than 20 degrees. In visual examination at 25 degrees and 30
      degrees an average clinician could diagnose the distortion. CONCLUSIONS: The X
      ray diagnosis of gap at the interface can be significantly influenced by the
      inclination of the X-ray tube in relation to the long axis of the implant. To
      achieve accurate results, the use of a paralleling device is advocated in order
      to achieve greater detection ability. CLINICAL RELEVANCE: Dental radiography is
      often used for detection of marginal gaps at the implant-abutment interface. The
      angulation of the X-ray beam may lead to inaccurate diagnosis in gap detection.
      The use of a paralleling device is indicated for evaluation of marginal accuracy.
      The geometry of the implant (internal or external hexagon) influences the gap
      evaluation.

PMID- 20690953
TI  - COMMENTARY. Radiographical evaluation of the gap at the implant-abutment
      interface.

PMID- 20690954
TI  - Morphologic texture characterization allied to cigarette smoke increase
      pigmentation in composite resin restorations.
AB  - STATEMENT OF THE PROBLEM: The staining effect of tobacco smoke on resin color is
      clinically observed. However, there is no evidence determining whether this
      staining is increased on texturized surfaces or if the color change is
      superficial and can be removed by repolishing procedures. OBJECTIVE: To evaluate
      the effect of tobacco smoke on the color of a composite with smooth or texturized
      surfaces, before and after repolishing. MATERIALS AND METHODS: Forty composite
      specimens were allocated into four groups (N = 10): Smooth surface not exposed
      (G1) and exposed to tobacco smoke (G2), texturized surface not exposed (G3), and
      exposed to tobacco smoke (G4). During 21 days, G2 and G4 were daily exposed to
      the smoke from 20 cigarettes. Color measurements were carried out at baseline,
      after 21 days, and after repolishing. Variables L* (luminosity), b* (blue
      yellow), and DeltaE (total color change) were statistically analyzed (repeated
      measures analysis of variance/Tukey). RESULTS: Texturized and smooth specimens
      presented similar luminosity at baseline. Tobacco smoke significantly reduced L*
      in G2 and G4, and increased b* in G4. After repolishing, L* increased and b*
      reduced in stained groups, but values continued to be different from baseline
      ones. Repolishing significantly reduced DeltaE, but values from stained groups
      were still greater than that from unstained groups. CONCLUSION: Tobacco smoke
      changes the color of composite, and surface texture can increase the staining.
      Repolishing reduces superficial staining, but this procedure may not return the
      composite to baseline color. CLINICAL RELEVANCE: Smokers that will receive
      anterior composite restorations should be warned about the negative cosmetic
      effect of the smoking habit on the color of restorations.

PMID- 20690955
TI  - COMMENTARY. Morphologic texture characterization allied to cigarette smoke
      increase pigmentation in composite resin restorations.

PMID- 20690956
TI  - Bond strength of two resin cements on dentin using different cementation
      strategies.
AB  - PURPOSE: This study evaluated the microtensile bond strength of two resin cements
      to dentin either with their corresponding self-etching adhesives or employing the
      three-step "etch-and-rinse" technique. The null hypothesis was that the "etch-and
      rinse" adhesive system would generate higher bond strengths than the self-etching
      adhesives. MATERIALS AND METHODS: Thirty-two human molars were randomly divided
      into four groups (N = 32, n = 8/per group): G1) ED Primer self-etching adhesive +
      Panavia F; G2) All-Bond 2 "etch-and-rinse" adhesive + Panavia F; G3) Multilink
      primer A/B self-etching adhesive + Multilink resin cement; G4) All-Bond 2 +
      Multilink. After cementation of composite resin blocks (5 x 5 x 4 mm), the
      specimens were stored in water (37 degrees C, 24 hours), and sectioned to obtain
      beams (+/-1 mm(2) of adhesive area) to be submitted to microtensile test. The
      data were analyzed using 2-way analysis of variance and Tukey's test (alpha =
      0.05). RESULTS: Although the cement type did not significantly affect the results
      (p = 0.35), a significant effect of the adhesive system (p = 0.0001) was found on
      the bond strength results. Interaction terms were not significant (p = 0.88751).
      The "etch-and-rinse" adhesive provided significantly higher bond strength values
      (MPa) with both resin cements (G2: 34.4 +/- 10.6; G4: 33.0 +/- 8.9) compared to
      the self-etching adhesive systems (G1: 19.8 +/- 6.6; G3: 17.8 +/- 7.2) (p <
      0.0001). Pretest failures were more frequent in the groups where self-etching
      systems were used. CONCLUSION: Although the cement type did not affect the
      results, there was a significant effect of changing the bonding strategy. The use
      of the three-step "etch-and-rinse" adhesive resulted in significantly higher bond
      strength for both resin cements on dentin. CLINICAL SIGNIFICANCE: Dual
      polymerized resin cements tested could deliver higher bond strength to dentin in
      combination with "etch-and-rinse" adhesive systems as opposed to their use in
      combination with self-etching adhesives.

PMID- 20690957
TI  - COMMENTARY. Bond strength of two resin cements on dentin using different
      cementation strategies.

PMID- 20690958
TI  - Critical appraisal. Options for dentin/enamel bonding: part IV.
AB  - Four categories of resin-based dentin/enamel adhesives are currently available.
      These include the three-step etch-&-rinse, "one-bottle" etch-&-rinse, two-step
      self-etch primer systems, and "all-in-one" self-etch adhesives. In consecutive
      issues of the Journal, the Critical Appraisal series is presenting salient
      publications on research in each of the categories. This final installment of the
      series focuses on the all-in-one self-etch adhesives.

PMID- 20690959
TI  - Indian isolates of white spot syndrome virus exhibit variations in their
      pathogenicity and genomic tandem repeats.
AB  - To detect genomic variation of white spot syndrome virus (WSSV) isolates from
      different geographical regions of India, the variable number of the tandem repeat
      (VNTR) region of the ORF 94 (Thailand WSSV isolate - GeneBank Accession No.
      AF369029) was analysed using five specific sets of primers. Analysis of 70 WSSV
      positive samples showed the presence of 14 different genotypes of WSSV with VNTRs
      ranging from 2 to 16 tandem repeats with the majority (85.47%) having 6-12 tandem
      repeats. Occurrence of different genotypes of WSSV was found to be neither
      correlated to any specific geographical region nor to the different growth stage
      of the tiger shrimp, Penaeus monodon. Pathogenicity studies conducted with 25
      isolates of WSSV revealed the presence of virulent and avirulent strains of WSSV
      in Indian shrimp farms. However, an unambiguous link could not be established
      between the different genotypes and their virulence.

PMID- 20690960
TI  - A variant of the interleukin-1beta gene in European sea bass, Dicentrarchus
      labrax L., is associated with increased resistance against Vibrio anguillarum.
AB  - Vibriosis caused by the pathogenic bacterium Vibrio (Listonella) anguillarum
      leads to serious losses in European sea bass, Dicentrarchus labrax. Because of
      its pleiotropic activity in controlling immune and inflammatory responses against
      various pathogens, interleukin-1beta (IL-1beta) is an attractive candidate for
      resistance to bacterial vibriosis. Four polymorphisms c.76 + 52C>T, c.76 +
      157A>G, c.76 + 215A>and c76 + 310A>G of IL1B were genotyped in progeny of four
      families of wild sea bass captured in geographically distinct regions of the
      Black Sea and Sea of Azov and challenged with V. anguillarum. In the transmission
      disequilibrium test, the TGGG haplotype of IL1B showed significant
      overtransmission from parents to surviving progeny, thereby suggesting an
      association with higher resistance to V. anguillarum infection (Odds Ratio 0.38,
      P < 10(-7)). Using a luciferase reporter assay, we found a 1.4-fold increase in
      transcription activity of the protective IL1B TGGG variant compared to the
      susceptible CAAA variant of IL1B. The higher transcriptional activity of IL1B
      TGGG may arise from the functional effects of c.76 + 157A>G and c.76 + 215A>G
      polymorphisms disrupting potential binding sites for glucocorticoid receptor and
      YY1, both are negative transcription regulators.

PMID- 20690961
TI  - Mycobacterium marinum infection in a hybrid striped bass farm in Italy.

PMID- 20690963
TI  - The efficacy of short daily dialysis--a single-centre experience.
AB  - Studies have shown that patients converted to short daily haemodialysis (SDHD)
      have reported many clinical benefits, decreased complications during dialysis and
      a better quality of life.A six-month prospective cohort study was conducted to
      examine the efficacy of SDHD to patients previously receiving three times per
      week haemodialysis therapy. Following informed consent, participants received
      haemodialysis daily, Monday-Saturday, between 2 and 2.5 hours for each treatment
      and followed-up for a six-month period. The participants continued to experience
      hypotension, cramping and headache and were noncompliant with fluid intake. There
      was a gradual reduction in blood pressure, cessation of antihypertensives and
      reduction of erythropoietin therapy (ERT). There were no hospital admissions or
      reports of access complications. The nursing staff reported an increase in
      activity levels and nursing interventions with the participants following
      conversion to SDHD. However, the participants reported a better quality of life.

PMID- 20690964
TI  - Quality of life of Greek patients with end stage renal disease undergoing
      haemodialysis.
AB  - An evaluation of the quality of life of patients with end stage kidney disease
      undergoing haemodialysis in the Greek population was conducted to understand
      whether this quality could be improved. Comparisons were made with a similar
      study conducted in United States in regards to the effects of kidney disease in
      daily life, burden of kidney disease, work status, cognitive function, quality of
      social interaction, sexual function, social support, physical functioning, role
      physical on daily routine, pain, general health perceptions, role emotional,
      emotional well being, social function and energy/fatigue. Any differences are
      discussed and analysed. Sexual problems were found to be more prominent in this
      study, but the emotional status has greater influence in quality of life in the
      US study. The results were more positive in Greece with respect to dialysis staff
      encouragement, patient satisfaction, as well as acceptance and the understanding
      of illness. The results from our study reflect the differences of the health care
      systems in various countries as well as population-related beliefs and values.

PMID- 20690965
TI  - Self-efficacy in relation to limited fluid intake amongst Portuguese
      haemodialysis patients.
AB  - Self-efficacy is a temporary and influenceable characteristic, related to
      situations and tasks, mediating health-promoting behaviours. This study aimed to
      evaluate psychometric properties of a Portuguese version of the Fluid Intake
      Appraisal Inventory, and to describe self-efficacy in relation to limited fluid
      intake amongst Portuguese haemodialysis patients. Respondents were recruited from
      three dialysis units, and 113 of 155 eligible patients gave their informed
      consent. The translated scale was distributed and collected by the head nurses.
      Interdialytic weight gain was calculated as percentage of dry weight.
      Satisfactory psychometric properties were estimated in the Portuguese context.
      The participants' self-efficacy in relation to low fluid intake was
      asymmetrically distributed; the majority had moderately to high self-efficacy
      while some patients had very low self-efficacy to limited fluid intake. There was
      a significant difference in self-efficacy to fluid restrictions; patients with a
      weight gain of 3.5% or less presented higher self-efficacy scores than did
      patients exceeding the cutoff point.

PMID- 20690966
TI  - Lifestyle in patients with chronic kidney disease is associated with less
      arterial stiffness.
AB  - Cardiovascular disease is the major cause of mortality in chronic kidney disease
      (CKD). Arterial stiffening is recognised as a critical precursor of
      cardiovascular disease. Available evidence indicates that lifestyle modifications
      are therapeutic interventions for preventing and treating arterial stiffening.
      OBJECTIVE: To evaluate the influence of lifestyle modifications on the arterial
      vessel compliance in CKD patients not receiving renal replacement therapy (RRT).
      We measured the arterial vessel compliance in 50 CKD patients not receiving RRT
      (30 post-transplant, 20 pre-RRT). Noninvasive pulse wave analysis of radial
      artery was used to estimate large artery (C1) and small artery elasticity (C2)
      and was corrected for patients age. Renal transplant (RT) patients were younger
      than CKD patients. RT patients C1 normal in 13%. C2 lower than normal in 77% of
      cases and not associated with evaluated variables, but worse large artery
      compliance was observed. In CKD patients, C1 was normal in 55%. C1 was strongly
      associated with aerobic exercise. For CKD patients, exercise normalises large
      artery compliance. C2 was lower than normal in 90%. Small artery compliance was
      affected in majority of patients.

PMID- 20690967
TI  - Riding the emotional rollercoaster: renal transplant from a doctor's perspective.
AB  - This account is of the pathway to a renal transplant. It is my feelings and
      conception of the journey acknowledging the psychological impact along the way.
      The workload before transplantation and my unappreciated desire to delay the
      operation are discussed. The search for the donor was difficult as I had to come
      to terms with being the person responsible for giving my mother pain and
      suffering. The outcome is good and my desire to thank my mother is overwhelming.

PMID- 20690968
TI  - Incidence and risk factors of transplant renal artery stenosis in living
      unrelated donor renal transplantation.
AB  - BACKGROUND: This study was designed to evaluate the incidence and risk factors of
      transplant renal artery stenosis (TRAS) among living donor unrelated kidney
      recipients. PATIENTS AND METHODS: Three hundred and sixty kidney consecutive
      transplant recipients were included in this retrospective cohort study. Informed
      written consent was obtained, only TRAS occurring three months after
      transplantation were considered. After five-year follow up, TRAS was established
      in 6.6% (24 patients) of patients. RESULTS: Mean +/- SD age of recipients was
      39.8 +/- 14.9 years old (range 16-77). Upon multivariate analysis recipient age
      >50 (RR = 2.9, CI 95%: 1.33-2.93, p = 0.008), recipient BMI >30 (kg/m(2)) (RR:
      7.97, CI 95%: 3.44-18.46, p < 0.001), retransplantation (RR = 4.88, CI 95%: 2.21
      10.77, p < 0.001), cytomegalovirus (CMV) infection and delayed graft function
      (DGF) (RR: 4.29, CI 95%: 3.12-13.79, p = 0.01) appeared to be independently
      associated with TRAS. Positive CMV-antibody was more frequent in recipients with
      TRAS (95.83% vs. 70.8%, p = 0.04) but all of them were HCV-antibody negative.
      Other variables as discussed were similar between two groups. CONCLUSION: High
      recipient age, BMI > 30, hyper trigelyceridaemia, previous transplantation, CMV
      infection and DGF are shown to be risk factors for TRAS.

PMID- 20690969
TI  - The green nephrology survey of sustainability in renal units in England, Scotland
      and Wales.
AB  - The impact of unmitigated climate change upon global health is predicted to be
      disastrous. However, the very provision of healthcare itself has a significant
      environmental impact, and the contribution of kidney care to the carbon footprint
      of the NHS is likely to be disproportionately high. Furthermore, the current
      economic climate will ensure that healthcare systems face unprecedented
      reductions in resources (or, at the very least, diminished expansion in the face
      of ongoing increases in demand). Improvements in the way that renal services use
      resources will address both issues. This survey was designed to identify a
      baseline for sustainability in kidney care, to support a clinical transformation
      to lower carbon kidney care by identifying fruitful areas for attention, and to
      act as an educational tool. The survey identified measures for improvement across
      the different areas of the provision of kidney care, including building energy
      use, patient and staff transport, water use and the consumption and procurement
      of resources. The results of the survey, which was completed by 58 adult and
      paediatric renal units across England, Scotland, and Wales, are reported here and
      potential changes are discussed.

PMID- 20690970
TI  - Incineration: why this may be the most environmentally sound method of renal
      healthcare waste disposal.
AB  - The environment and 'green' issues are currently being promoted in the healthcare
      sector through recently launched initiatives. This paper considers aspects of
      healthcare waste management, with particular reference to waste generated in
      dialysis units. With dialysis being dependent upon large amounts of disposables,
      it generates considerable volumes of waste. This paper focuses upon a typical
      haemodialysis unit, evaluating and quantifying the volumes and categories of
      waste generated. Each haemodialysis patient on thrice weekly dialysis generates
      some 323 kg per year of waste, of which 271 kg is classified as clinical. This
      equates to 1626 kg of (solid) clinical waste per dialysis bed, which is around
      three times the volume of clinical waste generated per general hospital bed.
      Waste disposal routes are considered and this suggests that present healthcare
      waste paradigms are outmoded. They do not allow for flexible approaches to
      solving what is a dynamic problem, and there is a need for new thinking models in
      terms of managing the unsustainable situation of disposal in constantly growing
      landfills. Healthcare waste management must be considered not only in terms of
      the environmental impact and potential long-term health effects, but also in
      terms of society's future energy requirements.

PMID- 20690973
TI  - The influence of physical and social contexts of eating on lunch-time food intake
      among southern Ontario, Canada, middle school students.
AB  - BACKGROUND: Among students, little is known about the physical and social context
      of eating lunch. The objective of this study was to determine if food intake
      (including the type of food and beverages and portion sizes) was associated with
      specific aspects of the physical and social lunch environment (location, with
      whom lunch was consumed, who prepared the food, and where the food was originally
      purchased). METHODS: A total of 1236 participants (males = 659, females = 566) in
      grades 6 (n = 359), 7 (n = 409), and 8 (n = 463) from southern Ontario, Canada,
      completed the Food Behavior Questionnaire during the 2005-2006 academic year.
      RESULTS: A total of 8159 foods and 2200 beverages were consumed during the lunch
      meal, which contributed to 552 kcal (SD = 429) or 30% (SD = 16) of total daily
      energy intake (kcal/day). Higher amounts of energy, meats and alternatives, other
      foods, fried foods, and pizza were consumed when participants ate in between
      places or at a restaurant/fast food outlet (compared with at home or school, p <
      0.05) and/or when prepared by friends or others (compared with themselves or
      family members, p < 0.05). A large number of participants (46%) reported
      consuming sugar-sweetened beverages during lunch, despite a school board-level
      policy restricting the sales of "junk food," which appears to be brought from
      home. CONCLUSIONS: Our findings support schools in policy efforts that restrict
      fast food access (by leaving school grounds, preventing fast food companies from
      coming onto school grounds, or restricting sugar-sweetened beverage sales in
      vending machines) and that eating in between places should be discouraged.

PMID- 20690974
TI  - Schoolchildren's consumption of competitive foods and beverages, excluding a la
      carte.
AB  - BACKGROUND: Competitive foods/beverages are those in school vending machines,
      school stores, snack bars, special sales, and items sold a la carte in the school
      cafeteria that compete with United States Department of Agriculture (USDA) meal
      program offerings. Grouping a la carte items with less nutritious items allowed
      in less regulated venues may obfuscate analysis of the school competitive food
      environment. Excluding a la carte items from competitive foods, the objectives
      were to: (1) assess competitive food use by gender, ethnicity, eligibility for
      free or reduced-price meals, and participation in school meals programs, (2)
      determine differences between grade levels in energy intakes obtained from food
      sources, (3) determine the nutrient intake derived from competitive foods for
      students who consumed them, and (4) determine energy-adjusted differences in 24
      hour nutrient intakes of protein, calcium, iron, and other selected nutrients
      between competitive food consumer and nonconsumers. METHODS: Competitive
      foods/beverages use, excluding a la carte items, was examined using the third
      School Nutrition Dietary Assessment Study (SNDA III), a nationally representative
      sample of 2309 schoolchildren in grades 1 to 12. Mean nutrient intakes were
      adjusted for energy intake and other covariates, and differences between
      consumers and nonconsumers of competitive items were determined using analysis of
      variance and sudaan. RESULTS: Excluding a la carte items, 22% of schoolchildren
      consumed competitive items in a representative school day and use was highest in
      high school. Consumers of competitive items other than a la carte had
      significantly higher mean energy, sugar intakes, and lower sodium, dietary fiber,
      B vitamins, and iron intakes than nonconsumers. CONCLUSIONS: Use of competitive
      foods/beverages, excluding a la carte, was detrimental to children's diet
      quality.

PMID- 20690975
TI  - Differences in children's recess physical activity: recess activity of the week
      intervention.
AB  - BACKGROUND: The increased prevalence in recent childhood obesity rates raises
      concern about youth health and the role that lack of physical activity plays in
      this trend. A focus on how children today choose to spend their discretionary
      time is one approach that may yield ideas for how to reduce childhood obesity.
      The purpose of the present study was to examine whether 3 separate recess
      activities of the week (RAWs) would make a difference in children's discretionary
      time physical activity levels. METHODS: Children (N = 65: 30 boys, 35 girls; 32
      first and second graders; 33 third and fourth graders; 45 healthy body mass index
      [BMI], 20 overweight BMI) at 1 Midwest elementary school wore pedometers for each
      15-minute morning recess period for 4 weeks. Following 1 no RAW (#1), a new RAW
      was introduced each subsequent week: #2, circuit course; #3, obstacle course; and
      #4, Frisbees. RESULTS: Repeated measures factorial analysis of variance results
      revealed that children were significantly more active during the no RAW and
      circuit course week than the Frisbee week. Males were significantly more
      physically active than females during the obstacle course week. Older children
      were significantly more active during the Frisbee week than younger children.
      Healthy BMI children were significantly more physically active during the circuit
      course week than children in the overweight/obese BMI category. CONCLUSIONS:
      Results imply that it is important for schools to consider demographic factors in
      the creation of recess opportunities to increase physical activity.

PMID- 20690976
TI  - A multilevel examination of school and student characteristics associated with
      physical education class enrollment among high school students.
AB  - BACKGROUND: Schools can be an efficient venue for promoting physical activity
      (PA) among adolescents. Physical education (PE) requires investigation because it
      is a variable associated with adolescent PA levels and its existence in schools
      represents a significant opportunity for strategies to combat declining PA levels
      among this population. This article examines the between-school variability in
      student rates of PE enrollment among a large sample of high schools in Ontario,
      Canada, and identifies the school- and student-level characteristics associated
      with PE enrollment. METHODS: This cross-sectional study utilized self-reported
      school- and student-level data from administrators and students at 73 high
      schools. Students' enrollment in PE, demographic, behavioral, and psychosocial
      variables was linked to school environment data comprising of school demographics
      and administrator assessed quality of policies, facilities, and programs related
      to PA. Analysis involved multilevel modeling. RESULTS: The mean rate of PE
      enrollment among the 73 high schools was 62.4%, with rates by school ranging from
      28.9% to 81.1%. When student demographics, behavioral, and psychosocial factors
      were controlled for, there was still a school effect for student PE enrollment.
      The school effect was explained by the provision of daily PE and school median
      household income. CONCLUSIONS: This is the first study to examine the extent to
      which PE enrollment varies between schools and to identify school factors
      associated with school variability in rates of PE enrollment. Although most
      variation in PE enrollment lies between students within schools, there is
      sufficient between-school variation to be of interest to practitioners and policy
      makers.

PMID- 20690977
TI  - Evaluation of a school-based train-the-trainer intervention program to teach
      first aid and risk reduction among high school students.
AB  - BACKGROUND: Farming is a hazardous occupation posing health risks from
      agricultural exposures for the farm owner and family members. First Aid for Rural
      Medical Emergencies (F.A.R.M.E.) was developed to support a train-the-trainer
      (TTT) program to prepare high school students to teach first aid skills and risk
      reduction through peer interaction. This study was designed to evaluate the
      educational effectiveness for first aid skill development and awareness of safety
      issues and injury prevention impacting agricultural communities. METHODS: Forty
      three agricultural science students from a rural high school participated in the
      study. A quasi-experimental design was used to evaluate knowledge acquisition and
      anticipatory action among groups: those participating in training and a
      comparison group with no training. The intervention group included 27
      participants trained as first aid peer instructors using the F.A.R.M.E. manual,
      return demonstration, case scenario facilitation training, and teaching
      evaluation sessions. The effectiveness of the program was evaluated using
      triangulated data. Independent t test analyses were conducted on post-test scores
      to evaluate the knowledge acquisition and anticipatory action scores between
      groups. Focus group sessions assessed attitudes, experiences, and values held
      following the intervention of teaching peers. RESULTS: Results indicate that the
      intervention group scored significantly higher on anticipatory action (t = 2.23,
      p = .03) but not knowledge acquisition (t = 1.37, p = .18). Focus group data
      suggest that the TTT format bolstered confidence in teaching, confirmed that
      teens enjoy learning from teens, and fostered pride in team work. CONCLUSIONS:
      The F.A.R.M.E. TTT resulted in a theory and evidence-based intervention that can
      be implemented in a school setting to promote knowledge and skill acquisition of
      first aid and injury prevention among rural high school students.

PMID- 20690979
TI  - Curcumin modulates leukocyte and platelet adhesion in murine sepsis.
AB  - OBJECTIVE: Circulating cell-endothelial cell interaction in sepsis is a rate
      determining factor in organ dysfunction, and interventions targeting this process
      have a potential therapeutic value. In this project, we examined whether
      curcumin, an active ingredient of turmeric and an anti-inflammatory agent, could
      disrupt interactions between circulating blood cells and endothelium and improve
      survival in a murine model of sepsis. METHODS: Mice were subjected to cecal
      ligation and puncture (CLP) to induce sepsis vs. sham surgery. We studied
      leukocyte and platelet adhesion in cerebral microcirculation using intravital
      fluorescent video microscopy technique, blood-brain barrier (BBB) dysfunction
      using Evans Blue (EB) leakage method, P-selectin expression using dual
      radiolabeling technique, and survival in mice subjected to Sham, CLP, and CLP
      with curcumin pre-treatment (CLP + curcumin). RESULTS: Curcumin significantly
      attenuated leukocyte and platelet adhesion in cerebral microcirculation, EB
      leakage in the brain tissue, and improved survival in mice with CLP. P-selectin
      expression in mice with CLP + curcumin was significantly attenuated compared with
      CLP in various microcirculatory beds, including brain. Reduction in platelet
      adhesion was predominantly via modulation of endothelium by curcumin. CONCLUSION:
      Curcumin pre-treatment modulates leukocyte and platelet adhesion and BBB
      dysfunction in mice with CLP via P-selectin expression and improves survival in
      mice with CLP.

PMID- 20690980
TI  - The cardio-protective properties of Ncx-6550, a nitric oxide donating
      pravastatin, in the mouse.
AB  - OBJECTIVE: Determine the cardio-protective properties of a nitric oxide-releasing
      pravastatin (Ncx-6550), in comparison to pravastatin. METHODS: A mouse model of
      myocardial infarct was used assessing tissue damage both at 2 and 24 hour post
      reperfusion, administering compounds both prophylactically and therapeutically.
      RESULTS: Ncx-6550 induced a significant dose-dependent (2.24-22.4 micromol/kg
      i.p.) cardioprotection in the two hour reperfusion protocol. In vehicle-treated
      mice, infarct size (expressed as fraction of area at risk; IS/AR) was 41.2 +/-
      1%, and it was reduced to 22.2 +/- 0.9% and 32.6 +/- 0.9% following 22.4 and 6.72
      micromol/kg Ncx-6550 (p < 0.05). 22.4 micromol/kg Ncx-6550 also increased cardiac
      levels of the enzyme heme oxygenase-1. Treatment of mice with pravastatin induced
      significant reduction of myocardial injury only at 22.4 micromol/kg (IS/AR value:
      33.7 +/- 0.9%). In a 24 hour reperfusion protocol, Ncx-6550 and pravastatin were
      tested only at 22.4 micromol/kg i.p. being given either one hour prior to
      ischemia (prophylactic protocol) or one hour into reperfusion (therapeutic
      protocol). With either treatment scheme, Ncx-6550 produced higher
      cardioprotection compared to pravastatin, as reflected also by a reduction in the
      incidence of lethality as well as in circulating troponin I and interleukin-1beta
      levels. CONCLUSIONS: These results indicate Ncx-6550 as a novel therapeutic agent
      with a potential for the treatment of myocardial infarct.

PMID- 20690981
TI  - Antecedent ethanol attenuates cerebral ischemia/reperfusion-induced leukocyte
      endothelial adhesive interactions and delayed neuronal death: role of large
      conductance, Ca2+-activated K+ channels.
AB  - EtOH-PC reduces postischemic neuronal injury in response to cerebral (I/R). We
      examined the mechanism underlying this protective effect by determining (i)
      whether it was associated with a decrease in I/R-induced leukocyte-endothelial
      adhesive interactions in postcapillary venules, and (ii) whether the protective
      effects were mediated by activation of large conductance, calcium-activated
      potassium (BK(Ca)) channels. Mice were administered ethanol by gavage or treated
      with the BK(Ca) channel opener, NS1619, 24 hours prior to I/R with or without
      prior treatment with the BK(Ca) channel blocker, PX. Both CCA were occluded for
      20 minutes followed by two and three hours of reperfusion, and rolling (LR) and
      adherent (LA) leukocytes were quantified in pial venules using intravital
      microscopy. The extent of DND, apoptosis and glial activation in hippocampus were
      assessed four days after I/R. Compared with sham, I/R elicited increases in LR
      and LA in pial venules and DND and apoptosis as well as glial activation in the
      hippocampus. These effects were attenuated by EtOH-PC or antecedent NS1619
      administration, and this protection was reversed by prior treatment with PX. Our
      results support a role for BK(Ca) channel activation in the neuroprotective
      effects of EtOH-PC in cerebral I/R.

PMID- 20690982
TI  - Inhibition of endothelin-1 receptors improves impaired nitric oxide synthase
      dependent dilation of cerebral arterioles in type-1 diabetic rats.
AB  - OBJECTIVE: Endothelin-1 has been implicated in the pathogenesis of many
      cardiovascular-related diseases, including diabetes. The goal of this study was
      to examine the influence of endothelin-1 receptors (ET(A)) in impaired responses
      of cerebral (pial) arterioles in type-1 diabetic rats. METHODS: We measured
      responses of cerebral arterioles in non-diabetic rats to endothelial nitric oxide
      synthase (eNOS)-dependent (ADP), neuronal nitric oxide synthase (nNOS)-dependent
      (N-methyl-d-aspartic acid [NMDA]) and NOS-independent (nitroglycerin) agonists
      before and during application of BQ-123, an ET(A) receptor antagonist. In
      addition, we harvested brain tissue from non-diabetic and diabetic rats to
      measure the production of superoxide anion under basal conditions and during
      inhibition of ET(A) receptors. RESULTS: We found that diabetes specifically
      impaired eNOS- and nNOS-dependent reactivity of cerebral arterioles, but did not
      alter NOS-independent vasodilation. In addition, while BQ-123 did not alter
      responses in non-diabetic rats, BQ-123 restored impaired eNOS- and nNOS-dependent
      vasodilation in diabetic rats. Further, superoxide production was higher in brain
      tissue from diabetic rats compared with non-diabetic rats under basal conditions
      and BQ-123 decreased basal production of superoxide in diabetic rats. CONCLUSION:
      We suggest that activation of ET(A) receptors during type-1 diabetes mellitus
      plays an important role in impaired eNOS- and nNOS-dependent dilation of cerebral
      arterioles.

PMID- 20690985
TI  - The place for innovation in nursing.

PMID- 20690983
TI  - VEGF-A promotes intussusceptive angiogenesis in the developing chicken
      chorioallantoic membrane.
AB  - OBJECTIVE: To assess the impact of vascular endothelial growth factor (VEGF) on
      intussusceptive angiogenesis. METHODS AND RESULTS: Polyurethane casts of the
      microvasculature of chicken chorioallantoic membrane (CAM) were prepared on
      embryonic days (E) 8, 10, 12, and 14. At light microscopy level, minute holes (<2
      microm in diameter) and hollows (>2 microm) were observed in the casts.
      Transmission electron microscopy disclosed the minute holes to mainly represent
      transluminal pillars characteristic for intussusceptive angiogenesis. The
      numerical density of the holes/pillars was highest at an early (E8) and a late
      (E12-E14) stage. Only mRNA of VEGF-A-122 and VEGF-A-166 isoforms was detected in
      the CAM. The transcription rate of VEGF-A mRNA peaked on E8/9 and E12, while VEGF
      A protein expression increased on E8/9 and E11/12 to rapidly decrease thereafter
      as determined by immunoblotting. At all time points investigated, VEGF-A
      immunohistochemical reactivity was restricted to cells of the chorionic
      epithelium in direct contact to the capillary plexus. When the VEGF-R-inhibitor
      PTK787/ZK222584 (0.1 mg/mL) was applied on E9 CAM, the microvasculature topology
      on E12 was similar to that on E10. CONCLUSIONS: The temporal course of
      intussusception corresponded to the expression of VEGF-A in CAM microvasculature.
      Inhibition of VEGF-signaling retarded intussusceptive-dependent capillary
      maturation. These data suggest that VEGF promotes intussusception.

PMID- 20690987
TI  - Creative controversy reply to editor: "rapid change".

PMID- 20690989
TI  - Competency education and validation in the United States: what should nurses
      know?
AB  - This article provides an overview of the progress in the past decade toward
      effectively documenting the initial and continuing competence of registered
      nurses.

PMID- 20690990
TI  - The gift of listening: JUST listening strategies.
AB  - The purpose of this paper is to examine how the simple act of listening deeply to
      patients serves as a potentially powerful tool in determining treatment plans,
      improving patient compliance, decreasing costs, increasing efficacy, and
      improving patient-practitioner relationships. Nonegoic listening is a
      transformative practice that can be integrated into clinical training and
      practice. A growing body of experiential and anecdotal evidence indicates that
      this is an area ripe for further investigation to enhance nursing interventions
      and cultural competencies. Given the significant role that advance practice
      nurses have in directing patient care, integrative listening can be valuable in
      shaping patient care.

PMID- 20690991
TI  - Mock webpage: an innovative assignment for second-degree nursing students.
AB  - Generating challenging and meaningful academic assignments for nursing students
      in which the student manages the technology used to deliver information is needed
      for accelerated second-degree nursing students. Developing those assignments is
      critical for keeping accelerated second-degree students engaged in the learning
      process. They are highly motivated, self-directed learners who have been found to
      have a preference for teaching-learning experiences that incorporate the use of
      technology. This paper describes the development of a mock webpage assignment to
      meet the learning needs of accelerated second-degree nursing students.

PMID- 20690992
TI  - Concept analysis: nurse-to-nurse lateral violence.
AB  - PURPOSE: The purpose of this paper is to examine the concept of nurse-to-nurse
      lateral violence (LV). SOURCE: Published literature--LV among nurses is
      significant and results in social, psychological, and physical consequences,
      negative patient and nursing outcomes, and damaged relationships. An extensive
      review of literature through Health Source, Cumulative Index to Nursing and
      Allied Health Literature (CINAHL), ProQuest health, and Medical Complete was used
      to determine agreement and disagreement across disciplines and emerging trends.
      CONCLUSION: This concept analysis demonstrates that nurse-to-nurse LV is nurse-to
      nurse aggression with overtly or covertly directing dissatisfaction toward
      another. Origins include role issues, oppression, strict hierarchy,
      disenfranchising work practices, low self-esteem, powerlessness perception,
      anger, and circuits of power. The result of this analysis provides guidance for
      further conceptual and empirical research as well as for clinical practice.
      Organizations must learn how to eliminate antecedents and provide nurses with
      skills and techniques to eradicate LV to improve the nursing work environment,
      patient care outcomes, and nurse retention.

PMID- 20690993
TI  - An appraisal of the factors influencing human sexuality research in nursing.
AB  - BACKGROUND: Conducting human sexuality research continues to be a challenge for
      nurse researchers and may seem daunting to nursing students interested in
      conducting human sexuality research. PURPOSE: The purpose of this paper was to
      conduct a comprehensive review of the literature to appraise the factors that
      have influenced human sexuality research for nurse researchers. FINDINGS: Various
      factors, both intrinsically and extrinsically to the nursing profession, have had
      an influence on human sexuality studies conducted by nurse researchers.
      CONCLUSION: A critical appraisal of the findings from the review of the
      literature provide implications for nurse researchers as well as students of
      nursing interested in conducting human sexuality research.

PMID- 20690994
TI  - A holistic framework for nursing time: implications for theory, practice, and
      research.
AB  - TOPIC: Nursing time has relevance for those who produce it, those who receive it,
      and those who must pay for it. Although the term nursing time may be commonly
      used, a common understanding of the concept within the fields of nursing and
      healthcare administration is lacking. PURPOSE: The purposes of this paper are to
      explore the concept of nursing time and to identify implications for theory
      development, clinical and administrative practice, and research. DISCUSSION: Both
      physical and psychological forms of time are viewed as fundamental to our
      experience of time as social beings. Nursing time has significant intrinsic and
      instrumental value in nursing and health care. A holistic approach incorporating
      the physical, psychological, and sociological aspects and dimensions of nursing
      time is advocated. CONCLUSIONS: Multiple strategies to enhance the patient
      experience of nursing time are warranted and should address how much time nurses
      spend with patients as well as how they spend that time. Patterns of overlapping
      and competing time structures for nurses should be identified and evaluated for
      their effect on physical time available for patient care and the psychological
      experiences of time by nurses and patients.

PMID- 20690995
TI  - An exploratory study of nurses' presence in daily care on an oncology unit.
AB  - PURPOSE/OBJECTIVES: Explore the use of presence among nurses on an oncology unit.
      PARTICIPANTS: Five oncology nurses and 10 assigned patients. METHOD: Descriptive
      qualitative study using participant observation, individual and group interviews.
      FINDINGS: Presence was embedded in each nurse's individual manner and approach,
      in the structure and nature of morning care, and in the nature of the individual
      patient situation. Nurses' presence varied based on patient cues. There was a
      similarity and pattern to the ways that nurses were present, suggesting an
      overall process that included three major phases in which the nurse moved from
      presence, to partial presence, and then full presence.
      INTERPRETATION/IMPLICATIONS: Morning care is an opportunity for the emergence of
      different ways of being present with the patient. Developing patient-nurse trust
      and responsiveness to patient cues is critical to the emergence of full presence.
      The nurse needs to be aware of potential stressors, whether personal or
      organizationally based, that could detract from the energy needed to be present.
      Nurses can use presence as a way to provide emotional support to patients who are
      exposed to overwhelming threats to their mind, body, and spiritual integrity.

PMID- 20690996
TI  - Perceptions of effective and ineffective nurse-physician communication in
      hospitals.
AB  - PROBLEM: Nurse-physician communication affects patient safety. Such communication
      has been well studied using a variety of survey and observational methods;
      however, missing from the literature is an investigation of what constitutes
      effective and ineffective interprofessional communication from the perspective of
      the professionals involved. The purpose of this study was to explore nurse and
      physician perceptions of effective and ineffective communication between the two
      professions. METHODS: Using focus group methodology, we asked nurses and
      physicians with at least 5 years' acute care hospital experience to reflect on
      effective and ineffective interprofessional communication and to provide
      examples. Three focus groups were held with 6 participants each (total sample
      18). Sessions were audio recorded and transcribed verbatim. Transcripts were
      coded into categories of effective and ineffective communication. FINDINGS: The
      following themes were found. For effective communication: clarity and precision
      of message that relies on verification, collaborative problem solving, calm and
      supportive demeanor under stress, maintenance of mutual respect, and authentic
      understanding of the unique role. For ineffective communication: making someone
      less than, dependence on electronic systems, and linguistic and cultural
      barriers. CONCLUSION: These themes may be useful in designing learning activities
      to promote effective interprofessional communication.

PMID- 20690997
TI  - Membership: priceless.

PMID- 20690998
TI  - Breast cancer type.

PMID- 20690999
TI  - Maternal obesity.

PMID- 20691002
TI  - Bottle/nipple systems.

PMID- 20691003
TI  - Safe infant sleeping.

PMID- 20691005
TI  - Promoting stringent glycemic control before and during pregnancy: evidence- and
      theory-based strategies.

PMID- 20691006
TI  - Embracing the electronic medical record: helping nurses overcome possible
      barriers.

PMID- 20691007
TI  - Formula-feeding safety: what nurses need to teach parents who choose to formula
      feed.

PMID- 20691008
TI  - Community-associated methicillin-resistant Staphylococcus aureus (MRSA): an
      overview for nurses.
AB  - Upon completion of this activity, the learner will be able to:1. Differentiate
      between the two types of Methicillin-resistant Staphylococcus aureus (MRSA)--HA
      MRSA and CA-MRSA. 2. Describe evidence-based management of MRSA infections. 3.
      Describe the epidemiology and clinical manifestations of MRSA infections.

PMID- 20691009
TI  - Carpal tunnel syndrome: coping during pregnancy and breastfeeding.

PMID- 20691010
TI  - Cultural diversity: what role does it play in patient safety?

PMID- 20691011
TI  - The story of type 1 diabetes.

PMID- 20691014
TI  - A journey through joy and grief.

PMID- 20691015
TI  - Immunoendocrine host-parasite interactions during helminth infections: from the
      basic knowledge to its possible therapeutic applications.
AB  - Most of the current research on parasitic infections that affect humans and
      domestic animals has been focused on vaccines, diagnostic methods, epidemiology,
      new drug design, and recently, with the advancement of genomics and proteomics,
      on the evolutionary origins of parasites. However, the basic biology of many
      parasites of medical and veterinary importance has not been intensively studied.
      Some efforts have been made to obtain information on the parasite-host
      relationship; however, knowledge of the intricate neuroimmunoendocrine
      interactions of the host-parasite network, the consequences of this interaction
      on the host and parasite physiology, and its possible applications needs further
      investigation. We review here the literature, our own studies on the host
      parasite neuroimmunoendocrine network, and how this basic knowledge can be used
      to design new treatments, by way of using hormones, antihormones, and hormone
      analogues as a possible novel therapy during parasitic diseases, with special
      emphasis on helminth parasites. Besides the biological interest, these
      investigations may contribute to the future identification of alternative
      treatments for several parasitic diseases. This complicated neuroimmunoendocrine
      network management during parasitic infections, and its physiological and
      behavioural consequences upon the host, may be operative in other mammalian
      infections. Such complexity may also help to explain the often conflicting
      results, observed between infections with respect to the role of the host sex and
      age, and hints to other avenues of research and strategies for their treatment
      and control.

PMID- 20691016
TI  - An early commitment to expression of a particular TCRVbeta chain on CD8(+) T
      cells responding to attenuated Plasmodium berghei sporozoites is maintained
      following challenge with infectious sporozoites.
AB  - Protection induced by irradiated Plasmodium berghei sporozoites (Pbgamma-spz) in
      mice is linked to CD8(+) T cells specific for exo-erythrocytic-stage Ags, and
      intrahepatic memory CD8(+) T cells are associated with protracted protection.
      However, the Ag specificity of the protective CD8(+) T cells remains largely
      unknown. In this study, we characterized the TCR Vbeta usage by intrahepatic
      CD8(+) T cells during gamma-spz immunization and after the challenge with
      infectious Pb sporozoites. The repertoire of naive (T(N)) and central memory
      (T(CM)) CD8(+) T cells was diverse and conserved between individual mice, and did
      not change with immunization. In contrast, preferential usage of one or more TCR
      Vbeta subset was observed in effector memory (T(EM)) CD8(+) T cells after
      immunization. The expanded TCR Vbeta varied between individual mice but Vbeta4,
      6, 7, 8.3, 9 and 11 were the most frequently expressed. In addition, there was a
      correlation in the TCR Vbeta usage by gamma-spz-induced CD8(+) T(EM) in the liver
      and blood of individual mice. The expansion pattern of blood CD8(+) T(EM) did not
      change with challenge and remained the same for 8 weeks thereafter. These results
      demonstrate that immunization with gamma-spz skews the TCR Vbeta repertoire of
      CD8(+) T(EM), and commitment to a particular TCR Vbeta expression is maintained
      long-term.

PMID- 20691017
TI  - Protective immunization of calves against Ostertagia ostertagi using fourth stage
      larval extracts.
AB  - ConA lectin was used to isolate glycoproteins from detergent extracts of fourth
      stage Ostertagia ostertagi larvae. This preparation contained proteins additional
      to those observed in a similar fraction prepared from adult O. ostertagi. Two
      vaccine trials were conducted with this preparation, and sub-fractions thereof,
      in groups of 6-8 worm-free calves. All groups were challenged with 50,000 O.
      ostertagi larvae 1 week after the final immunization, and protection was assessed
      by comparing the egg and worm counts of the immunized groups with their
      respective controls. Immunization with the ConA-binding antigen or its sub
      fractions induced high titre serum antibody responses. In the first trial, the
      cumulative egg count of the group immunized with unfractionated antigen was 60%
      lower than the corresponding control value, and worm counts were 47% lower. In
      the second trial, the cumulative egg counts of the vaccinated groups ranged from
      70% to 85% lower than the corresponding controls, with worm counts up to 64%
      lower. It was concluded that detergent-soluble, ConA-binding extracts prepared
      from O. ostertagi fourth stage larvae contained protective immunogens that were
      as effective as the best antigens published for O. ostertagi to date.

PMID- 20691018
TI  - Protection against Naegleria fowleri infection in mice immunized with Cry1Ac plus
      amoebic lysates is dependent on the STAT6 Th2 response.
AB  - We previously reported that intranasal administration of Cry1Ac protoxin alone or
      in combination with amoebic lysates increases protection against Naegleria
      fowleri meningoencephalitis in mice. Those results suggested that both antibody
      responses and innate immune mechanisms may be participating in the protective
      effects observed. The present study was aimed to investigate whether the STAT6
      induced Th2 immune response is essential for the resistance to N. fowleri
      infection, conferred by immunization with amoebic lysates plus Cry1Ac. STAT6
      deficient (STAT6-/-) and wild-type (STAT6+/+) BALB/c mice were immunized by the
      intranasal route with a combination of N. fowleri lysates plus Cry1Ac, and
      subsequently challenged with lethal doses of N. fowleri trophozoites. STAT6+/+
      mice displayed 100% protection, while no protection was observed in STAT6-/-
      mice. Significantly higher titres of Th2-associated IgG1 as well as interleukin-4
      (IL-4) were found in STAT6+/+ mice, whereas in STAT6-/- mice significantly more
      IL-12 and IFN-gamma as well as significantly higher titres of Th1-associated
      IgG2a were detected. Thus, whereas protected STAT6+/+-immunized mice elicited a
      Th-2 type inclined immune response that produced predominantly humoral immunity,
      unprotected STAT6-/- mice exhibited a polarized Th1 type cellular response. These
      findings suggest that the STAT6-signalling pathway is critical for defence
      against N. fowleri infection.

PMID- 20691019
TI  - Immunological response of sheep to injections of plasmids encoding Toxoplasma
      gondii SAG1 and ROP1 genes.
AB  - Infection with the intracellular protozoan parasite Toxoplasma gondii (T. gondii)
      causes health problems to both humans and livestock and has a large economic
      impact worldwide. The immune response in sheep following infection with T. gondii
      was evaluated using six different combinations of plasmid DNA, recombinant
      antigen and adjuvant. Sheep were generally vaccinated twice by intramuscular
      injection with plasmid DNA containing gene sequences for either the surface
      antigen (SAG1) or the rhoptry protein (ROP1) of T. gondii. Two of the groups
      injected with plasmid DNA SAG1 were boosted with recombinant protein (SAG1). We
      investigated the efficacy of including oligodeoxynucleotides (ODN) that contain
      CG motifs (CpG) and the gene coding for ovine granulocyte-macrophage colony
      stimulating factor (GM-CSF) as potential adjuvants. Administration of the plasmid
      encoding the ROP1 gene significantly enhanced both IFN-gamma production from
      peripheral blood cells when cultured in vitro with Toxoplasma antigen, and ROP1
      specific IgG1 and IgG2 antibody levels present in serum. However, injection with
      SAG1 did not stimulate IFN-gamma production. These results indicate the potential
      of ROP1, given as plasmid DNA, as a potential vaccine candidate to protect sheep
      against T. gondii infection.

PMID- 20691020
TI  - Variation in the cellular localization of host-protective oncospheral antigens in
      Taenia saginata and Taenia solium.
AB  - Immunohistochemistry and immunofluorescence with confocal microscopy were used to
      localize the host-protective antigens of Taenia saginata (TSA9 and TSA18) and
      Taenia solium (TSOL16, TSOL18 and TSOL45). In nonactivated oncospheres, TSA9 and
      TSOL45 antigens were found primarily in the cytoplasm of the penetration gland
      type one (PG1) cell. A similar pattern of staining was seen for TSOL45 in
      oncospheres of T. solium that remained within the oncospheral membrane. In
      addition, there was less intense staining of TSA9 and TSOL45 in the quadri
      nucleate penetration gland type 2 (PG2) cell. TSA18, TSOL16 and TSOL18 were
      predominantly found in the PG2 cell. In activated oncospheres that had escaped
      the oncospheral membrane, the antigens (other than TSA9) were seen both in the
      penetration gland cell locations and throughout the oncospheral parenchyma. Co
      localization analyses revealed that only TSOL16 and TSOL18 antigens were co
      localized in the PG2 cell of oncospheres that had not escaped the oncospheral
      membrane. However, in activated oncospheres that escaped the oncospheral
      membrane, all three antigens of T. solium were co-localized as they were present
      throughout the parenchyma. No positive staining was observed on the surface of
      nonactivated or recently activated oncospheres of T. saginata or T. solium.

PMID- 20691021
TI  - Ex vivo assessment of serum cytokines in patients with cystic echinococcosis of
      the liver.
AB  - To investigate the usefulness of serum cytokine levels in the diagnosis of active
      cystic echinococcosis, we evaluated the cytokine profile of patients with hepatic
      cystic echinococcosis in different cyst stages, CE 1-2 (active), CE3a-3b
      (transitional) and CE4-5 (inactive). Ex vivo assessment of Th1 (IL12, TNFalpha)
      and Th2 (IL4, IL10) cytokines in sera was carried out using ELISA. Percentages of
      positive samples and median levels of IL12, TNFalpha and IL10 did not differ
      significantly between groups. However, patients with CE3b cysts, a stage
      clinically unresponsive to treatments, had statistically significantly higher
      median levels of IL4 and percentage of positive samples for IL4. We conclude that
      the analysis of serum cytokine dosage, at least in its present form, is not
      useful as a marker of cyst activity. However, our results support recent findings
      suggesting the chronic activity of CE3b cysts and suggest that this might be
      partly because of a skewed Th2 response.

PMID- 20691022
TI  - Overexpression of hydroperoxide lyase gene in Nicotiana benthamiana using a viral
      vector system.
AB  - 13-Lipoxygenase (13-LOX) and 13-hydroperoxide lyases (13-HPL) are the key enzymes
      for the production of the 'green note' compounds hexanal, (3Z)- and (2E)-hexenal
      in plant tissues. To produce high levels of 13-LOX and 13-HPL enzymatic
      activities for a biocatalytic process to generate C(6)-aldehydes on a large
      scale, soya bean 13-LOX (GmVLXC) and watermelon 13-HPL (ClHPL) genes were
      expressed in Nicotiana benthamiana using a viral vector system mediated by
      agroinfiltration. The N. benthamiana leaves produced high activity of watermelon
      HPL, but not GmVLXC 13-LOX. In addition, all leaves treated with bacterial
      suspension displayed a high activity of 9-LOX, indicating that the internal
      tobacco 9-LOX gene was highly induced through agroinfiltration because of
      wounding. GmVLXC and ClHPL transcripts could be detected in the corresponding
      transformed tobacco leaves by real-time RT-PCR analysis but the expression level
      of ClHPL was 24-fold higher than that of GmVLXC. Western blot analysis showed
      that LOX was present in all tobacco leaves which were treated with bacterial
      suspensions, but not in the untreated wild-type control. This result confirms
      that internal 9-LOX was highly induced by agroinfiltration. The highest levels of
      ClHPL activity under optimal infiltration conditions were 80 times the HPL
      activity of wild-type plants or plants transformed with control vector. A large
      amount of hexanal was formed when linoleic acid was incubated with extracts from
      N. benthamiana leaves over-expressing ClHPL in combination with GmVLXC-expressing
      yeast extracts. One gram of ClHPL-expressing N. benthamiana leaves (fresh weight)
      could produce 17 +/- 0.4 mg hexanal from 50 mg linoleic acid after 30 min.

PMID- 20691023
TI  - Seed-specific overexpression of antioxidant genes in Arabidopsis enhances
      oxidative stress tolerance during germination and early seedling growth.
AB  - Enzymatic and non-enzymatic antioxidants play important roles in the tolerance of
      abiotic stress. To increase the resistance of seeds to oxidative stress, At2S3
      promoter from Arabidopsis was used to achieve overexpression of the antioxidants
      in a seed-specific manner. This promoter was shown to be capable of driving the
      target gene to have a high level of expression in seed-related organs, including
      siliques, mature seeds, and early seedlings, thus making its molecular farming
      applications in plants possible. Subsequently, genes encoding Mn-superoxide
      dismutase (MSD1), catalase (CAT1), and homogentisate phytyltransferase (HPT1,
      responsible for the first committed reaction in the tocopherol biosynthesis
      pathway) were overexpressed in Arabidopsis under the control of the At2S3
      promoter. Double overexpressers co-expressing two enzymes and triple
      overexpressers were produced by cross pollination. Mn-SOD and total CAT
      activities, as well as gamma-tocopherol content, significantly increased in the
      corresponding overproduction lines. Moreover, single MSD1-transgene, double, and
      triple overexpressers displayed remarkably enhanced oxidative stress tolerance
      compared to wild type during seed germination and early seedling growth.
      Interestingly, an increase in the total CAT activity was also observed in the
      single MSD1-transgenic lines as a result of MSD1 overexpression. Together, the
      combined increase in Mn-SOD and CAT activities in seeds plays an essential role
      in the improvement of antioxidant capacity at early developmental stage in
      Arabidopsis.

PMID- 20691024
TI  - Abstracts of the Fiftieth Annual Meeting of the Society for Psychophysiological
      Research. Portland, Oregon, USA. September 29-October 3, 2010.

PMID- 20691025
TI  - PET/CT today and tomorrow in veterinary cancer diagnosis and monitoring:
      fundamentals, early results and future perspectives.
AB  - Functional imaging using positron emission tomography (PET) plays an important
      role in the diagnosis, staging, image-guided treatment planning and monitoring of
      malignant diseases. PET imaging complements conventional anatomical imaging such
      as computed tomography (CT) and magnetic resonance imaging (MRI). The strength of
      CT scanning lies in its high spatial resolution, allowing for anatomical
      characterization of disease. PET imaging, however, moves beyond anatomy and
      characterizes tissue based on functions such as metabolic rate. Combined PET/CT
      scanners were introduced commercially in 2001 and a number of technological
      advancements have since occurred. Radiolabelled tracers such as (18)F
      fluorodeoxyglucose (FDG) and (18)F-fluorothymidine (FLT) allow visualization of
      various metabolic processes within cancer cells. Many studies in human oncology
      evaluating the utility of PET/CT have demonstrated clinical benefits. Few
      veterinary studies have been performed, but initial studies show promise for
      improved detection of malignancy, more thorough staging of canine cancer and
      determination of early response and disease recrudescence.

PMID- 20691026
TI  - Doxorubicin and cyclophosphamide for the treatment of canine lymphoma: a
      randomized, placebo-controlled study.
AB  - Median survival times (STs) for doxorubicin-treated canine lymphoma range from
      5.7 to 9 months. Because dogs treated with multi-agent protocols have longer STs,
      we sought to evaluate whether adding cyclophosphamide would improve outcome in
      canine lymphoma patients while maintaining an acceptable level of toxicity.
      Thirty-two dogs with stage III-V multicentric lymphoma were treated with
      doxorubicin every 3 weeks for five total cycles and prednisone at a tapering dose
      for the first 4 weeks. Dogs were randomized to receive either cyclophosphamide or
      placebo concurrently. Seventeen dogs received doxorubicin and placebo, while 15
      dogs received doxorubicin and cyclophosphamide. Response, toxicity, progression
      free interval (PFI) and ST were evaluated. The combination of doxorubicin and
      cyclophosphamide was well tolerated, causing no increase in adverse events over
      doxorubicin alone. Despite a numeric improvement in outcome in cyclophosphamide
      treated dogs, the addition of cyclophosphamide did not result in statistically
      improved response rate, PFI or ST.

PMID- 20691027
TI  - Outcome and toxicity associated with a dose-intensified, maintenance-free CHOP
      based chemotherapy protocol in canine lymphoma: 130 cases.
AB  - A dose-intensified/dose-dense chemotherapy protocol for canine lymphoma was
      designed and implemented at the Veterinary Hospital of the University of
      Pennsylvania. In this study, we describe the clinical characteristics, prognostic
      factors, efficacy and toxicity in 130 dogs treated with this protocol. The
      majority of the dogs had advanced stage disease (63.1% stage V) and sub-stage b
      (58.5%). The median time to progression (TTP) and lymphoma-specific survival were
      219 and 323 days, respectively. These results are similar to previous less dose
      intense protocols. Sub-stage was a significant negative prognostic factor for
      survival. The incidence of toxicity was high; 53.9 and 45% of the dogs needed
      dose reductions and treatment delays, respectively. Dogs that required dose
      reductions and treatment delays had significantly longer TTP and lymphoma
      specific survival times. These results suggest that dose density is important,
      but likely relative, and needs to be adjusted according to the individual
      patient's toxicity for optimal outcome.

PMID- 20691028
TI  - Calcitriol (1,25-dihydroxycholecalciferol) enhances mast cell tumour chemotherapy
      and receptor tyrosine kinase inhibitor activity in vitro and has single-agent
      activity against spontaneously occurring canine mast cell tumours.
AB  - Calcitriol potentiates the effect of multiple chemotherapy agents in a variety of
      tumour models. In this study, we examine whether calcitriol increases
      chemotherapy or tyrosine kinase inhibitor in vitro cytotoxicity in canine
      mastocytoma C2 cells. We also evaluate the in vivo effect of DN101, a highly
      concentrated oral formulation of calcitriol designed specifically for cancer
      therapy, as a single-agent therapy in dogs with mast cell tumours (MCTs).
      Calcitriol exhibits synergistic, antiproliferative activity when used in
      combination with CCNU, vinblastine, imatinib or toceranib in vitro. The
      concentrations required for 50% growth inhibition were generally two- to six-fold
      lower when the drugs were used in combination than when used individually. High
      dose oral calcitriol induced remission in 4 of 10 dogs (one complete remission,
      three partial remissions), although the majority experienced toxicity,
      necessitating discontinuation of the trial. Further evaluation of calcitriol in
      combination therapy for dogs with MCTs is warranted.

PMID- 20691029
TI  - Efficacy of doxorubicin-based chemotherapy for non-resectable canine subcutaneous
      haemangiosarcoma.
AB  - Eighteen dogs with measurable subcutaneous haemangiosarcoma (SQHSA) were treated
      with doxorubicin-based chemotherapy. Response assessment was evaluated and
      compared using World Health Organization (WHO), Response Evaluation Criteria in
      Solid Tumours (RECIST) and tumour volume criteria. The overall response rate for
      all dogs was 38.8% using WHO criteria, 38.8% using RECIST criteria and 44% using
      tumour volume criteria. One dog had a complete response. The median response
      duration for all dogs was 53 days (range 13-190 days). Four dogs had complete
      surgical excision after neoadjuvant chemotherapy. The median progression-free
      interval for dogs with complete surgical excision after neoadjuvant chemotherapy
      was significantly longer than those not having surgical excision (207 days versus
      83 days, respectively) (P = 0.003). No significant difference in metastasis-free
      interval or survival time was found between the groups. Doxorubicin-based
      chemotherapy appears to be effective for non-resectable canine SQHSA, although
      the response duration is relatively short.

PMID- 20691030
TI  - Letters to the editor and rebuttal regarding the paper recently published in
      Veterinary and Comparative Oncology, 'Feline intestinal sclerosing mast cell
      tumour: 50 cases (1997-2008) 2010; 8: 72-79' by C. H. C. Halsey, B. E. Powers and
      D. A. Kamstock. Letter to the editor #1.

PMID- 20691031
TI  - Letters to the editor and rebuttal regarding the paper recently published in
      Veterinary and Comparative Oncology, 'Feline intestinal sclerosing mast cell
      tumour: 50 cases (1997-2008) 2010; 8: 72-79' by C. H. C. Halsey, B. E. Powers and
      D. A. Kamstock. Letter to the editor #2.

PMID- 20691033
TI  - Molecular basis for defect in Alix-binding by alternatively spliced isoform of
      ALG-2 (ALG-2DeltaGF122) and structural roles of F122 in target recognition.
AB  - BACKGROUND: ALG-2 (a gene product of PDCD6) belongs to the penta-EF-hand (PEF)
      protein family and Ca2+-dependently interacts with various intracellular proteins
      including mammalian Alix, an adaptor protein in the ESCRT system. Our previous X
      ray crystal structural analyses revealed that binding of Ca2+ to EF3 enables the
      side chain of R125 to move enough to make a primary hydrophobic pocket (Pocket 1)
      accessible to a short fragment of Alix. The side chain of F122, facing a
      secondary hydrophobic pocket (Pocket 2), interacts with the Alix peptide. An
      alternatively spliced shorter isoform, designated ALG-2DeltaGF122, lacks
      Gly121Phe122 and does not bind Alix, but the structural basis of the incompetence
      has remained to be elucidated. RESULTS: We solved the X-ray crystal structure of
      the PEF domain of ALG-2DeltaGF122 in the Ca2+-bound form and compared it with
      that of ALG-2. Deletion of the two residues shortened alpha-helix 5 (alpha5) and
      changed the configuration of the R125 side chain so that it partially blocked
      Pocket 1. A wall created by the main chain of 121-GFG-123 and facing the two
      pockets was destroyed. Surprisingly, however, substitution of F122 with Ala or
      Gly, but not with Trp, increased the Alix-binding capacity in binding assays. The
      F122 substitutions exhibited different effects on binding of ALG-2 to other known
      interacting proteins, including TSG101 (Tumor susceptibility gene 101) and
      annexin A11. The X-ray crystal structure of the F122A mutant revealed that
      removal of the bulky F122 side chain not only created an additional open space in
      Pocket 2 but also abolished inter-helix interactions with W95 and V98 (present in
      alpha4) and that alpha5 inclined away from alpha4 to expand Pocket 2, suggesting
      acquirement of more appropriate positioning of the interacting residues to accept
      Alix. CONCLUSIONS: We found that the inability of the two-residue shorter ALG-2
      isoform to bind Alix is not due to the absence of bulky side chain of F122 but
      due to deformation of a main-chain wall facing pockets 1 and 2. Moreover, a
      residue at the position of F122 contributes to target specificity and a smaller
      side chain is preferable for Alix binding but not favored to bind annexin A11.

PMID- 20691034
TI  - Daptomycin as a possible new treatment option for surgical management of
      Methicillin-Resistant Staphylococcus aureus sternal wound infection after cardiac
      surgery.
AB  - We present a case of a 77-year old female who had undergone a coronary artery
      bypass grafting with an aortic valve replacement and developed three month later
      a Methicillin-Resistant Staphylococcus aureus (MRSA) sternal wound infection
      which was successful treated with Daptomycin combined with vacuum-assisted
      closure (VAC).

PMID- 20691035
TI  - The relationship between sales of SSRI, TCA and suicide rates in the Nordic
      countries.
AB  - BACKGROUND: In the period 1990-2006, strong and almost equivalent increases in
      sales figures of selective serotonin re-uptake inhibitors (SSRIs) were observed
      in all Nordic countries. The sales figures of tricyclic antidepressants (TCAs)
      dropped in Norway and Sweden in the nineties. After 2000, sales figures of TCAs
      have been almost constant in all Nordic countries. The potentially toxic effect
      of TCAs in overdose was an important reason for replacing TCAs with SSRIs when
      treating depression. We studied whether the rapid increase in sales of SSRIs and
      the corresponding decline in TCAs in the period 1990-98 were associated with a
      decline in suicide rates. METHODS: Aggregated suicide rates for the period 1975
      2006 in four Nordic countries (Denmark, Finland, Norway and Sweden) were obtained
      from the national causes-of-death registries. The sales figures of
      antidepressants were provided from the wholesale registers in each of the Nordic
      countries. Data were analysed using Fisher's exact test and Pearson's correlation
      coefficient. RESULTS: There was no statistical association (P = 1.0) between the
      increase of sales figures of SSRIs and the decline in suicide rates. There was no
      statistical association (P = 1.0) between the decrease in the sale figures of
      TCAs and change in suicide rates either. CONCLUSIONS: We found no evidence for
      the rapid increase in use of SSRIs and the corresponding decline in sales of TCAs
      being associated with a decline in the suicide rates in the Nordic countries in
      the period 1990-98. We did not find any inverse relationship between the increase
      in sales of SSRIs and declining suicide rates in four Nordic countries.

PMID- 20691037
TI  - Global parameter estimation methods for stochastic biochemical systems.
AB  - BACKGROUND: The importance of stochasticity in cellular processes having low
      number of molecules has resulted in the development of stochastic models such as
      chemical master equation. As in other modelling frameworks, the accompanying rate
      constants are important for the end-applications like analyzing system properties
      (e.g. robustness) or predicting the effects of genetic perturbations. Prior
      knowledge of kinetic constants is usually limited and the model identification
      routine typically includes parameter estimation from experimental data. Although
      the subject of parameter estimation is well-established for deterministic models,
      it is not yet routine for the chemical master equation. In addition, recent
      advances in measurement technology have made the quantification of genetic
      substrates possible to single molecular levels. Thus, the purpose of this work is
      to develop practical and effective methods for estimating kinetic model
      parameters in the chemical master equation and other stochastic models from
      single cell and cell population experimental data. RESULTS: Three parameter
      estimation methods are proposed based on the maximum likelihood and density
      function distance, including probability and cumulative density functions. Since
      stochastic models such as chemical master equations are typically solved using a
      Monte Carlo approach in which only a finite number of Monte Carlo realizations
      are computationally practical, specific considerations are given to account for
      the effect of finite sampling in the histogram binning of the state density
      functions. Applications to three practical case studies showed that while maximum
      likelihood method can effectively handle low replicate measurements, the density
      function distance methods, particularly the cumulative density function distance
      estimation, are more robust in estimating the parameters with consistently higher
      accuracy, even for systems showing multimodality. CONCLUSIONS: The parameter
      estimation methodologies described in this work have provided an effective and
      practical approach in the estimation of kinetic parameters of stochastic systems
      from either sparse or dense cell population data. Nevertheless, similar to
      kinetic parameter estimation in other modelling frameworks, not all parameters
      can be estimated accurately, which is a common problem arising from the lack of
      complete parameter identifiability from the available data.

PMID- 20691038
TI  - Using Abbreviated Injury Scale (AIS) codes to classify Computed Tomography (CT)
      features in the Marshall System.
AB  - BACKGROUND: The purpose of Abbreviated Injury Scale (AIS) is to code various
      types of Traumatic Brain Injuries (TBI) based on their anatomical location and
      severity. The Marshall CT Classification is used to identify those subgroups of
      brain injured patients at higher risk of deterioration or mortality. The purpose
      of this study is to determine whether and how AIS coding can be translated to the
      Marshall Classification METHODS: Initially, a Marshall Class was allocated to
      each AIS code through cross-tabulation. This was agreed upon through several
      discussion meetings with experts from both fields (clinicians and AIS coders).
      Furthermore, in order to make this translation possible, some necessary
      assumptions with regards to coding and classification of mass lesions and brain
      swelling were essential which were all approved and made explicit. RESULTS: The
      proposed method involves two stages: firstly to determine all possible Marshall
      Classes which a given patient can attract based on allocated AIS codes; via cross
      tabulation and secondly to assign one Marshall Class to each patient through an
      algorithm. CONCLUSION: This method can be easily programmed in computer softwares
      and it would enable future important TBI research programs using trauma registry
      data.

PMID- 20691039
TI  - Multiple myeloma presenting as spinal cord compression: a case report.
AB  - INTRODUCTION: Spinal cord compression is a potentially devastating condition that
      demands immediate attention. Efforts must be divided between addressing the
      symptoms of cord compression and identifying the precise etiology of the
      condition. CASE PRESENTATION: A 76-year-old Peruvian man presented to our
      emergency department for evaluation of the gradual onset of lower extremity
      weakness over one month, resulting in falls and a two day history of bladder and
      bowel incontinence. Surprisingly, the etiology of this case of spinal cord
      compression was found to be multiple myeloma presenting as a solid tumor.
      CONCLUSION: We report a case of a spinal cord mass resulting in symptoms of cord
      compression that was diagnosed when aspects of our patient's initial magnetic
      resonance imaging scan did not correlate with disc herniation, which was the
      diagnosis with the greatest pretest probability.

PMID- 20691040
TI  - DIRECT trial. Diverticulitis recurrences or continuing symptoms: Operative versus
      conservative treatment. A multicenter randomised clinical trial.
AB  - BACKGROUND: Persisting abdominal complaints are common after an episode of
      diverticulitis treated conservatively. Furthermore, some patients develop
      frequent recurrences. These two groups of patients suffer greatly from their
      disease, as shown by impaired health related quality of life and increased costs
      due to multiple specialist consultations, pain medication and productivity
      losses.Both conservative and operative management of patients with persisting
      abdominal complaints after an episode of diverticulitis and/or frequently
      recurring diverticulitis are applied. However, direct comparison by a randomised
      controlled trial is necessary to determine which is superior in relieving
      symptoms, optimising health related quality of life, minimising costs and
      preventing diverticulitis recurrences against acceptable morbidity and mortality
      associated with surgery or the occurrence of a complicated recurrence after
      conservative management.We, therefore, constructed a randomised clinical trial
      comparing these two treatment strategies. METHODS/DESIGN: The DIRECT trial is a
      multicenter randomised clinical trial. Patients (18-75 years) presenting
      themselves with persisting abdominal complaints after an episode of
      diverticulitis and/or three or more recurrences within 2 years will be included
      and randomised. Patients randomised for conservative treatment are treated
      according to the current daily practice (antibiotics, analgetics and/or expectant
      management). Patients randomised for elective resection will undergo an elective
      resection of the affected colon segment. Preferably, a laparoscopic approach is
      used.The primary outcome is health related quality of life measured by the Gastro
      intestinal Quality of Life Index, Short-Form 36, EQ-5D and a visual analogue
      scale for pain quantification. Secondary endpoints are morbidity, mortality and
      total costs. The total follow-up will be three years. DISCUSSION: Considering the
      high incidence and the multicenter design of this study, it may be assumed that
      the number of patients needed for this study (n = 214), may be gathered within
      one and a half year.Depending on the expertise and available equipment, we prefer
      to perform a laparoscopic resection on patients randomised for elective surgery.
      Should this be impossible, an open technique may be used as this also reflects
      the current situation. TRIAL REGISTRATION: (Trial register number: NTR1478).

PMID- 20691041
TI  - Reproductive life disorders in Italian celiac women. A case-control study.
AB  - BACKGROUND: The aim of this study is to explore the association between celiac
      disease and menstrual cycle, gestation and puerperal disorders. METHODS: The
      association between celiac disease and menstrual cycle, gestation and puerperal
      disorders in a sample of 62 childbearing age women (15-49 age) was assessed
      within an age and town of residence matched case-control study conducted in 2008.
      Main outcome measures were the presence of one or more disorders in menstrual
      cycle and the presence of one or more complication during pregnancy. RESULTS: 62
      celiac women (median age: 31.5, range: 17-49) and 186 healthy control (median
      age: 32.5, range: 15-49) were interviewed. A higher percentage of menstrual cycle
      disorders has been observed in celiac women. 19.4% frequency of amenorrhea was
      reported among celiac women versus 2.2% among healthy controls (OR = 33, 95% CI =
      7.17-151.8;, p = 0.000). An association has been observed between celiac disease
      and oligomenorrhea, hypomenorrhea, dysmenorrhea and metrorrhagia (p < 0.05). The
      likelihood of having at least one complication during pregnancy has been
      estimated to be at least four times higher in celiac women than in healthy women
      (OR = 4.1, 95% CI = 2-8.6, p = 0.000). A significant correlation has emerged for
      celiac disease and threatened abortion, gestational hypertension, placenta
      abruption, severe anaemia, uterine hyperkinesia, intrauterine growth restriction
      (p < 0.001). A shorter gestation has on average been observed in celiac women
      together with a lower birth weight of celiac women babies (p < 0.001).
      CONCLUSIONS: The occurrence of a significant correlation between celiac disease
      and reproductive disorders could suggest to consider celiac disease diagnostic
      procedures (serological screening) in women affected by these disorders.

PMID- 20691042
TI  - Physical training in boys with Duchenne Muscular Dystrophy: the protocol of the
      No Use is Disuse study.
AB  - BACKGROUND: "Use it or lose it" is a well known saying which is applicable to
      boys with Duchenne Muscular Dystrophy (DMD). Besides the direct effects of the
      muscular dystrophy, the increasing effort to perform activities, the fear of
      falling and the use of personal aids indirectly impair leg and arm functions as a
      result of disuse. Physical training could oppose this secondary physical
      deterioration. The No Use is Disuse (NUD) study is the first study in human
      subjects with DMD that will examine whether a low-intensity physical training is
      beneficial in terms of preservation of muscle endurance and functional abilities.
      The study consists of two training intervention studies: study 1 "Dynamic leg and
      arm training for ambulant and recently wheelchair-dependent boys with DMD and,
      study 2 "Functional training with arm support for boys with DMD who have been
      confined to a wheelchair for several years". This paper describes the hypotheses
      and methods of the NUD study. METHODS: Study 1 is an explorative randomized
      controlled trial with multiple baseline measurements. Thirty boys with a DNA
      established diagnosis of DMD will be included. The intervention consists of a six
      months physical training during which boys train their legs and arms with active
      and/or assisted cycling training equipment. The primary study outcomes are muscle
      endurance and functional abilities, assessed with a Six-Minute Bicycle Test and
      the Motor Function Measure. Study 2 has a within-group repeated measurements
      design and will include ten boys with DMD who have already been confined to a
      wheelchair for several years. The six-months physical training program consists
      of 1) a computer-assisted training and 2) a functional training with an arm
      support. The primary study outcome is functional abilities of the upper
      extremity, assessed with the Action Research Arm Test. DISCUSSION: The NUD study
      will fill part of the gap in the current knowledge about the possible effects of
      training in boys with DMD and will increase insight into what type of exercise
      should be recommended to boys with DMD. The study will finish at the end of 2010
      and results are expected in 2011. TRIAL REGISTRATION: The Netherlands National
      Trial Register1631.

PMID- 20691043
TI  - Columnar cell lesions and subsequent breast cancer risk: a nested case-control
      study.
AB  - INTRODUCTION: Histologic and genetic evidence suggests that at least some
      columnar cell lesions (CCL) of the breast represent precursor lesions in the low
      grade breast neoplasia pathway. However, the risk of subsequent breast cancer
      associated with the presence of CCL in a benign breast biopsy is poorly
      understood. METHODS: The authors examined the association between the presence of
      CCL and subsequent breast cancer risk in a nested case-control study of benign
      breast disease (BBD) and breast cancer within the Nurses' Health Studies (394
      cases, 1,606 controls). Benign breast biopsy slides were reviewed by pathologists
      and CCL presence assessed. Logistic regression was used to compute odds ratios
      (ORs) and 95% confidence intervals (CIs) for the association between CCL and
      breast cancer risk. RESULTS: Women with CCL (140 cases, 448 controls) had an
      increased risk of breast cancer compared with those without CCL (OR = 1.44, 95%
      CI: 1.14 to 1.83), although this was attenuated and became non-significant after
      adjustment for the histologic category of BBD (OR = 1.20, 95% CI: 0.94 to 1.54).
      CCL presence was associated with the greatest risk of breast cancer for those
      with nonproliferative BBD (OR = 1.36, 95% CI: 0.79 to 2.37) and the lowest risk
      for those with atypical hyperplasia (AH) (OR = 1.10, 95% CI: 0.65 to 1.87);
      however, this apparent heterogeneity in risk across BBD categories was not
      significant (P for interaction between CCL presence and BBD category = 0.77).
      CONCLUSIONS: These results provide evidence that CCL may be an important marker
      of breast cancer risk in women with BBD but suggest that CCL do not increase
      breast cancer risk independently of concurrent proliferative changes in the
      breast.

PMID- 20691044
TI  - Millicurrent stimulation of human articular chondrocytes cultivated in a collagen
      type-I gel and of human osteochondral explants.
AB  - BACKGROUND: Here we investigate the effect of millicurrent treatment on human
      chondrocytes cultivated in a collagen gel matrix and on human osteochondral
      explants. METHODS: Human chondrocytes from osteoarthritic knee joints were
      enzymatically released and transferred into a collagen type-I gel. Osteochondral
      explants and cell-seeded gel samples were cultivated in-vitro for three weeks.
      Samples of the verum groups were stimulated every two days by millicurrent
      treatment (3 mA, sinusoidal signal of 312 Hz amplitude modulated by two super
      imposed signals of 0.28 Hz), while control samples remained unaffected. After
      recovery, collagen type-I, type-II, aggrecan, interleukin-1beta, IL-6, TNFalpha
      and MMP13 were examined by immunohistochemistry and by real time PCR. RESULTS:
      With regard to the immunostainings 3 D gel samples and osteochondral explants did
      not show any differences between treatment and control group. The expression of
      all investigated genes of the 3 D gel samples was elevated following millicurrent
      treatment. While osteochondral explant gene expression of col-I, col-II and Il
      1beta was nearly unaffected, aggrecan gene expression was elevated. Following
      millicurrent treatment, IL-6, TNFalpha, and MMP13 gene expression decreased. In
      general, the standard deviations of the gene expression data were high, resulting
      in rarely significant results. CONCLUSIONS: We conclude that millicurrent
      stimulation of human osteoarthritic chondrocytes cultivated in a 3 D collagen gel
      and of osteochondral explants directly influences cell metabolism.

PMID- 20691045
TI  - Growth, immune and viral responses in HIV infected African children receiving
      highly active antiretroviral therapy: a prospective cohort study.
AB  - BACKGROUND: Scale up of paediatric antiretroviral therapy in resource limited
      settings continues despite limited access to routine laboratory monitoring. We
      documented the weight and height responses in HIV infected Ugandan children on
      highly active antiretroviral therapy and determined clinical factors associated
      with successful treatment outcomes. METHODS: A prospective cohort of HIV infected
      children were initiated on HAART and followed for 48 weeks. Body mass index for
      age z scores(BAZ), weight and height-for-age z scores (WAZ & HAZ) were
      calculated: CD4 cell % and HIV-1 RNA were measured at baseline and every 12
      weeks. Treatment outcomes were classified according to; both virological and
      immunological success (VS/IS), virological failure and immunological success
      (VF/IS). virological success and immunological failure (VS/IF) and both
      virological and immunological failure (VF/IF). RESULTS: From March 2004 until May
      2006, 124 HIV infected children were initiated on HAART. The median age (IQR) was
      5.0 years (2.1 - 7.0) and 49% (61/124) were female. The median [95% confidence
      interval (CI)] BAZ, WAZ and HAZ at baseline were 0.29 (-2.9, -1.2), -1.2 (-2.1, 
      0.5) and -2.06 (-2.9, -1.2) respectively. Baseline median CD4 cell % and log10
      HIV-1 RNA were; 11.8% (7.5-18.0) and 5.6 (5.2-5.8) copies/ml. By 48 weeks, mean
      WAZ and HAZ in the VF/IS group, which was younger, increased from - 0.98 (SD 1.7)
      to + 1.22 (SD 1.2) and from -1.99 (1.7) to + 0.76 (2.4) respectively. Mean
      increase in WAZ and HAZ in the VS/IF group, an older group was modest, from -1.84
      (1.3) to - 0.41 (1.2) and -2.25 (1.2) to -1.16 (1.3) respectively. Baseline CD4
      cell % [OR 6.97 95% CI (2.6 -18.6)], age [OR 4.6 95% CI (1.14 -19.1)] and WHO
      clinical stage [OR 3.5 95%CI (1.05 -12.7)] were associated with successful
      treatment outcome. CONCLUSIONS: HIV infected Ugandan children demonstrated a
      robust increase in height and weight z scores during the first 48 weeks of HAART,
      including those who failed to completely suppress virus. Older children
      initiating HAART with severe immune suppression were less likely to achieve a
      successful treatment outcome. These data emphasize the importance of initiating
      HAART early to ensure adequate immune and growth responses.

PMID- 20691046
TI  - Involvement of the Reck tumor suppressor protein in maternal and embryonic
      vascular remodeling in mice.
AB  - BACKGROUND: Developmental angiogenesis proceeds through multiple morphogenetic
      events including sprouting, intussusception, and pruning. Mice lacking the
      membrane-anchored metalloproteinase regulator Reck die in utero around embryonic
      day 10.5 with halted vascular development; however, the mechanisms by which this
      phenotype arises remain unclear. RESULTS: We found that Reck is abundantly
      expressed in the cells associated with blood vessels undergoing angiogenesis or
      remodelling in the uteri of pregnant female mice. Some of the Reck-positive
      vessels show morphological features consistent with non-sprouting angiogenesis.
      Treatment with a vector expressing a small hairpin RNA against Reck severely
      disrupts the formation of blood vessels with a compact, round lumen. Similar
      defects were found in the vasculature of Reck-deficient or Reck conditional
      knockout embryos. CONCLUSIONS: Our findings implicate Reck in vascular
      remodeling, possibly through non-sprouting angiogenesis, in both maternal and
      embyonic tissues.

PMID- 20691047
TI  - RankProdIt: A web-interactive Rank Products analysis tool.
AB  - BACKGROUND: The first objective of a DNA microarray experiment is typically to
      generate a list of genes or probes that are found to be differentially expressed
      or represented (in the case of comparative genomic hybridizations and/or copy
      number variation) between two conditions or strains. Rank Products analysis
      comprises a robust algorithm for deriving such lists from microarray experiments
      that comprise small numbers of replicates, for example, less than the number
      required for the commonly used t-test. Currently, users wishing to apply Rank
      Products analysis to their own microarray data sets have been restricted to the
      use of command line-based software which can limit its usage within the
      biological community. FINDINGS: Here we have developed a web interface to
      existing Rank Products analysis tools allowing users to quickly process their
      data in an intuitive and step-wise manner to obtain the respective Rank Product
      or Rank Sum, probability of false prediction and p-values in a downloadable file.
      CONCLUSIONS: The online interactive Rank Products analysis tool RankProdIt, for
      analysis of any data set containing measurements for multiple replicated
      conditions, is available at: http://strep
      microarray.sbs.surrey.ac.uk/RankProducts.

PMID- 20691048
TI  - What would PCR assessment change in the management of fevers in a malaria endemic
      area? A school-based study in Benin in children with and without fever.
AB  - BACKGROUND: A recent school-based study in Benin showed that applying a policy of
      anti-malarial prescriptions restricted to parasitologically-confirmed cases on
      the management of fever is safe and feasible. Additional PCR data were analysed
      in order to touch patho-physiological issues, such as the usefulness of PCR in
      the management of malaria in an endemic area or the triggering of a malaria
      attack in children with submicroscopic malaria. METHODS: PCR data were
      prospectively collected in the setting of an exposed (with fever)/non exposed
      (without fever) study design. All children had a negative malaria rapid
      diagnostic test (RDT) at baseline, were followed up to day 14 and did not receive
      drugs with anti-malarial activity. The index group was defined by children with
      fever at baseline and the control group by children without fever at baseline.
      Children with submicroscopic malaria in these two groups were defined by a
      positive PCR at baseline. RESULTS: PCR was positive in 66 (27%) children of the
      index group and in 104 (44%) children of the control group respectively. The only
      significant factor positively related to PCR positivity at baseline was the
      clinical status (control group). When definition of malaria attacks included PCR
      results, no difference of malaria incidence was observed between the index and
      control groups, neither in the whole cohort, nor in children with submicroscopic
      malaria. The rate of undiagnosed malaria at baseline was estimated to 3.7% at
      baseline in the index group. CONCLUSIONS: Treating all children with fever and a
      positive PCR would have led to a significant increase of anti-malarial
      consumption, with few benefits in terms of clinical events. Non malarial fevers
      do not or do not frequently trigger malaria attacks in children with
      submicroscopic malaria.

PMID- 20691049
TI  - Discontinuation of standard first-line antiretroviral therapy in a cohort of 1434
      Malawian children.
AB  - The standard first-line antiretroviral (ART) regimen in Malawi for both adults
      and children is a fixed-dose combination tablet containing stavudine (d4T),
      lamivudine (3TC) and nevirapine (NVP). This regimen has been shown to yield
      satisfactory virologic and immunologic outcomes in children. Published studies
      have described insights into discontinuation of first-line regimen and toxicities
      of ART in adults, but similar studies in paediatric populations are lacking. A
      retrospective cohort study was undertaken to assess reasons for discontinuation
      of the standard first-line ART regimen (d4T/3TC/NVP) in a paediatric population.
      In total, 1434 patients met eligibility criteria and were included. The cohort
      had mean and median age at ART initiation of 4.7 years and 2.9 years,
      respectively (range: 0.1 months-18.7 years). The gender distribution was 47%
      female and 53% male. Median follow-up time on ART was 1.8 years (range: 2 weeks
      3.9 years). A majority (96.2%) of patients were on the standard first-line ART
      regimen, while 3.8% (54) were on a different regimen. Twenty-eight patients
      (2.0%) were on an alternative first-line regimen due to toxicities, 22 patients
      (1.5%) were on a second-line regimen due to ART failure, and four patients (0.3%)
      were on a non-standard regimen for other clinical reasons. Of the 28 patients who
      experienced toxicities requiring ART regimen change, 60.7% (17) were caused by
      NVP, 39.3% (11) by d4T, and none by 3TC. The median time from first-line ART
      initiation to alternative first-line ART was two months (range: 10 days-28.1
      months); 60.7% of patients on alternative first-line ART were male. Average time
      on ART until switch to second-line ART regimen was 16.3 months (SD: 9.3 months).
      The probability of failure after one year on first-line regimen was 1.6% (95% CI:
      0.9-2.6). There was no compelling evidence in this cohort, representing
      approximately 10% of all children on ART in Malawi, to support changing the
      standard paediatric first-line regimen based on early toxicities or failure.
      However, experience from the national adult cohort, longer term follow up of the
      paediatric cohort in this study, emerging data on resistance after single-dose
      NVP containing mother to child transmission antiretroviral prophylaxis, and new
      2009 World Health Organization ART recommendations may influence national policy
      change to a different first-line regimen.

PMID- 20691050
TI  - Fatal cold agglutinin-induced haemolytic anaemia: a case report.
AB  - INTRODUCTION: Cold agglutinin disease usually develops as a result of the
      production of a specific immunoglobulin M auto-antibody directed against the I/i
      and H antigens, precursors of the ABH and Lewis blood group substances, on red
      blood cells. Autoimmune and lymphoproliferative disorders, Mycoplasma pneumoniae
      and other infections can be associated with the production of cold agglutinins.
      In its classic presentation with haemolytic anaemia and Raynaud's syndrome, cold
      agglutinin disease is usually idiopathic. Several factors play a role in
      determining the ability of a cold agglutinin to induce a haemolytic anaemia such
      as antibody concentration and temperature range, in particular the highest
      temperature at which antibodies interact with red blood cells. CASE PRESENTATION:
      A 48-year-old Caucasian man presented to our hospital with symptoms of extreme
      asthenia caused by severe anaemia. The transfusion of red blood cells (O Rh
      positive), started as prescribed by the emergency guidelines in force without pre
      transfusion tests, induced fatal haemolysis because of the presence of high
      levels of anti-H antibodies in his blood, that reacted with the large amount of H
      antigen in universal (0) red blood cells. CONCLUSION: Emergency transfusion of
      universal red blood cells (0 Rh-positive or negative) is usually accepted by the
      international guidelines in force in emergency departments. In this report we
      describe a rare complication caused by the very high concentration in the
      recipient of cold agglutinins and the activation of the complement system,
      responsible for red blood cell lysis and consequent fatal cardiovascular shock.
      We conclude that emergency transfusion of universal red blood cells (0 Rh
      positive or negative) may be dangerous and its risk should be assessed against
      the risk of delaying transfusion until the pre-transfusion tests are completed.

PMID- 20691051
TI  - Primary care nurses: effects on secondary care referrals for diabetes.
AB  - BACKGROUND: Primary care nurses play an important role in diabetes care, and were
      introduced in GP-practice partly to shift care from hospital to primary care. The
      aim of this study was to assess whether the referral rate for hospital treatment
      for diabetes type II (T2DM) patients has changed with the introduction of primary
      care nurses, and whether these changes were related to the number of diabetes
      related contacts in a general practice. METHODS: Healthcare utilisation was
      assessed for a period of 365 days for 301 newly diagnosed and 2124 known T2DM
      patients in 2004 and 450 and 3226 patients in 2006 from general practices that
      participated in the Netherlands Information Network of General Practice (LINH).
      Multilevel logistic and linear regression analyses were used to analyse the
      effect of the introduction of primary care nurses on referrals to internists,
      ophthalmologists and cardiologists and diabetes-related contact rate. Separate
      analyses were conducted for newly diagnosed and known T2DM patients. RESULTS:
      Referrals to internists for newly diagnosed T2DM patients decreased between 2004
      and 2006 (OR:0.44; 95%CI:0.22-0.87) in all practices. For known T2DM patients no
      overall decrease in referrals to internists was found, but practices with a
      primary care nurse had a lower trend (OR:0.59). The number of diabetes-related
      contacts did not differ between practices with and without primary care nurses.
      Cardiologists' and ophthalmologists' referral rate did not change. CONCLUSIONS:
      The introduction of primary care nurses seems to have led to a shift of care from
      internists to primary care for known diabetes patients, while the diabetes
      related contact rate seem to have remained unchanged.

PMID- 20691052
TI  - Subchronic oral toxicity of silver nanoparticles.
AB  - BACKGROUND: The antibacterial effect of silver nanoparticles has resulted in
      their extensive application in health, electronic, consumer, medicinal,
      pesticide, and home products; however, silver nanoparticles remain a
      controversial area of research with respect to their toxicity in biological and
      ecological systems. RESULTS: This study tested the oral toxicity of silver
      nanoparticles (56 nm) over a period of 13 weeks (90 days) in F344 rats following
      Organization for Economic Cooperation and Development (OECD) test guideline 408
      and Good Laboratory Practices (GLP). Five-week-old rats, weighing about 99 g for
      the males and 92 g for the females, were divided into four 4 groups (10 rats in
      each group): vehicle control, low-dose (30 mg/kg), middle-dose (125 mg/kg), and
      high-dose (500 mg/kg). After 90 days of exposure, clinical chemistry, hematology,
      histopathology, and silver distribution were studied. There was a significant
      decrease (P < 0.05) in the body weight of male rats after 4 weeks of exposure,
      although there were no significant changes in food or water consumption during
      the study period. Significant dose-dependent changes were found in alkaline
      phosphatase and cholesterol for the male and female rats, indicating that
      exposure to more than 125 mg/kg of silver nanoparticles may result in slight
      liver damage. Histopathologic examination revealed a higher incidence of bile
      duct hyperplasia, with or without necrosis, fibrosis, and/or pigmentation, in
      treated animals. There was also a dose-dependent accumulation of silver in all
      tissues examined. A gender-related difference in the accumulation of silver was
      noted in the kidneys, with a twofold increase in female kidneys compared to male
      kidneys. CONCLUSIONS: The target organ for the silver nanoparticles was found to
      be the liver in both the male and female rats. A NOAEL (no observable adverse
      effect level) of 30 mg/kg and LOAEL (lowest observable adverse effect level) of
      125 mg/kg are suggested from the present study.

PMID- 20691053
TI  - PeakAnalyzer: genome-wide annotation of chromatin binding and modification loci.
AB  - BACKGROUND: Functional genomic studies involving high-throughput sequencing and
      tiling array applications, such as ChIP-seq and ChIP-chip, generate large numbers
      of experimentally-derived signal peaks across the genome under study. In
      analyzing these loci to determine their potential regulatory functions, areas of
      signal enrichment must be considered relative to proximal genes and regulatory
      elements annotated throughout the target genome Regions of chromatin association
      by transcriptional regulators should be distinguished as individual binding sites
      in order to enhance downstream analyses, such as the identification of known and
      novel consensus motifs. RESULTS: PeakAnalyzer is a set of high-performance
      utilities for the automated processing of experimentally-derived peak regions and
      annotation of genomic loci. The programs can accurately subdivide multimodal
      regions of signal enrichment into distinct subpeaks corresponding to binding
      sites or chromatin modifications, retrieve genomic sequences encompassing the
      computed subpeak summits, and identify positional features of interest such as
      intersection with exon/intron gene components, proximity to up- or downstream
      transcriptional start sites and cis-regulatory elements. The software can be
      configured to run either as a pipeline component for high-throughput analyses, or
      as a cross-platform desktop application with an intuitive user interface.
      CONCLUSIONS: PeakAnalyzer comprises a number of utilities essential for ChIP-seq
      and ChIP-chip data analysis. High-performance implementations are provided for
      Unix pipeline integration along with a GUI version for interactive use. Source
      code in C++ and Java is provided, as are native binaries for Linux, Mac OS X and
      Windows systems.

PMID- 20691054
TI  - RoBuST: an integrated genomics resource for the root and bulb crop families
      Apiaceae and Alliaceae.
AB  - BACKGROUND: Root and bulb vegetables (RBV) include carrots, celeriac (root
      celery), parsnips (Apiaceae), onions, garlic, and leek (Alliaceae)--food crops
      grown globally and consumed worldwide. Few data analysis platforms are currently
      available where data collection, annotation and integration initiatives are
      focused on RBV plant groups. Scientists working on RBV include breeders,
      geneticists, taxonomists, plant pathologists, and plant physiologists who use
      genomic data for a wide range of activities including the development of
      molecular genetic maps, delineation of taxonomic relationships, and investigation
      of molecular aspects of gene expression in biochemical pathways and disease
      responses. With genomic data coming from such diverse areas of plant science,
      availability of a community resource focused on these RBV data types would be of
      great interest to this scientific community. DESCRIPTION: The RoBuST database has
      been developed to initiate a platform for collecting and organizing genomic
      information useful for RBV researchers. The current release of RoBuST contains
      genomics data for 294 Alliaceae and 816 Apiaceae plant species and has the
      following features: (1) comprehensive sequence annotations of 3663 genes 5959
      RNAs, 22,723 ESTs and 11,438 regulatory sequence elements from Apiaceae and
      Alliaceae plant families; (2) graphical tools for visualization and analysis of
      sequence data; (3) access to traits, biosynthetic pathways, genetic linkage maps
      and molecular taxonomy data associated with Alliaceae and Apiaceae plants; and
      (4) comprehensive plant splice signal repository of 659,369 splice signals
      collected from 6015 plant species for comparative analysis of plant splicing
      patterns. CONCLUSIONS: RoBuST, available at http://robust.genome.com, provides an
      integrated platform for researchers to effortlessly explore and analyze genomic
      data associated with root and bulb vegetables.

PMID- 20691055
TI  - Use of the GenoType(R) MTBDRplus assay to assess drug resistance of Mycobacterium
      tuberculosis isolates from patients in rural Uganda.
AB  - BACKGROUND: Drug resistance levels and patterns among Mycobacterium tuberculosis
      isolates from newly diagnosed and previously treated tuberculosis patients in
      Mbarara Uganda were investigated. METHODS: We enrolled, consecutively, all newly
      diagnosed and previously treated smear-positive TB patients aged >/= 18 years.
      Isolates were tested for drug resistance against rifampicin (RIF) and isoniazid
      (INH) using the Genotype(R) MDRTBplus assay and results were compared with those
      obtained by the indirect proportion method on Lowenstein-Jensen media. HIV
      testing was performed using two rapid HIV tests. RESULTS: A total of 125 isolates
      from 167 TB suspects with a mean age 33.7 years and HIV prevalence of 67.9%
      (55/81) were analysed. A majority (92.8%) of the participants were newly
      presenting while only 7.2% were retreatment cases. Resistance mutations to either
      RIF or INH were detected in 6.4% of the total isolates. Multidrug resistance, INH
      and RIF resistance was 1.6%, 3.2% and 4.8%, respectively. The rpobeta gene
      mutations seen in the sample were D516V, S531L, H526Y H526 D and D516V, while one
      strain had a Delta1 mutation in the wild type probes. There were three strains
      with katG (codon 315) gene mutations while only one strain showed the inhA
      promoter region gene mutation. CONCLUSION: The TB resistance rate in Mbarara is
      relatively low. The GenoType(R) MTBDRplus assay can be used for rapid screening
      of MDR-TB in this setting.

PMID- 20691056
TI  - Dual mobility cup reduces dislocation rate after arthroplasty for femoral neck
      fracture.
AB  - BACKGROUND: Hip dislocation after arthroplasty for femoral neck fractures remains
      a serious complication. The aim of our study was to investigate the dislocation
      rate in acute femoral neck fracture patients operated with a posterior approach
      with cemented conventional or dual articulation acetabular components. METHODS:
      We compared the dislocation rate in 56 consecutive patients operated with
      conventional (single mobility) cemented acetabular components to that in 42
      consecutive patients operated with dual articulation acetabular components. All
      the patients were operated via posterior approach and were followed up to one
      year postoperatively. RESULTS: There were 8 dislocations in the 56 patients
      having conventional components as compared to no dislocations in those 42 having
      dual articulation components (p = 0.01). The groups were similar with respect to
      age and gender distribution. CONCLUSIONS: We conclude that the use of a cemented
      dual articulation acetabular component significantly reduces the dislocation
      rates in femoral neck fracture patients operated via posterior approach.

PMID- 20691057
TI  - Genetic integrity of the human Y chromosome exposed to groundwater arsenic.
AB  - BACKGROUND: Arsenic is a known human carcinogen reported to cause chromosomal
      deletions and genetic anomalies in cultured cells. The vast human population
      inhabiting the Ganges delta in West Bengal, India and Bangladesh is exposed to
      critical levels of arsenic present in the groundwater. The genetic and
      physiological mechanism of arsenic toxicity in the human body is yet to be fully
      established. In addition, lack of animal models has made work on this line even
      more challenging. METHODS: Human male blood samples were collected with their
      informed consent from 5 districts in West Bengal having groundwater arsenic level
      more than 50 microg/L. Isolation of genomic DNA and preparation of metaphase
      chromosomes was done using standard protocols. End point PCR was performed for
      established sequence tagged sites to ascertain the status of recombination
      events. Single nucleotide variants of candidate genes and amplicons were carried
      out using appropriate restriction enzymes. The copy number of DYZ1 array per
      haploid genome was calculated using real time PCR and its chromosomal
      localization was done by fluorescence in-situ hybridization (FISH). RESULTS: We
      studied effects of arsenic exposure on the human Y chromosome in males from
      different areas of West Bengal focusing on known recombination events (P5-P1
      proximal; P5-P1 distal; gr/gr; TSPY-TSPY, b1/b3 and b2/b3), single nucleotide
      variants (SNVs) of a few candidate Y-linked genes (DAZ, TTY4, BPY2, GOLGA2LY) and
      the amplicons of AZFc region. Also, possible chromosomal reorganization of DYZ1
      repeat arrays was analyzed. Barring a few microdeletions, no major changes were
      detected in blood DNA samples. SNV analysis showed a difference in some alleles.
      Similarly, DYZ1 arrays signals detected by FISH were found to be affected in some
      males. CONCLUSIONS: Our Y chromosome analysis suggests that the same is protected
      from the effects of arsenic by some unknown mechanisms maintaining its structural
      and functional integrities. Thus, arsenic effects on the human body seem to be
      different compared to that on the cultured cells.

PMID- 20691058
TI  - Caspase inhibitors affect the kinetics and dimensions of tracheary elements in
      xylogenic Zinnia (Zinnia elegans) cell cultures.
AB  - BACKGROUND: The xylem vascular system is composed of fused dead, hollow cells
      called tracheary elements (TEs) that originate through trans-differentiation of
      root and shoot cambium cells. TEs undergo autolysis as they differentiate and
      mature. The final stage of the formation of TEs in plants is the death of the
      involved cells, a process showing some similarities to programmed cell death
      (PCD) in animal systems. Plant proteases with functional similarity to proteases
      involved in mammalian apoptotic cell death (caspases) are suggested as an
      integral part of the core mechanism of most PCD responses in plants, but
      participation of plant caspase-like proteases in TE PCD has not yet been
      documented. RESULTS: Confocal microscopic images revealed the consecutive stages
      of TE formation in Zinnia cells during trans-differentiation. Application of the
      caspase inhibitors Z-Asp-CH2-DCB, Ac-YVAD-CMK and Ac-DEVD-CHO affected the
      kinetics of formation and the dimensions of the TEs resulting in a significant
      delay of TE formation, production of larger TEs and in elimination of the 'two
      wave' pattern of TE production. DNA breakdown and appearance of TUNEL-positive
      nuclei was observed in xylogenic cultures and this was suppressed in the presence
      of caspase inhibitors. CONCLUSIONS: To the best of our knowledge this is the
      first report showing that caspase inhibitors can modulate the process of trans
      differentiation in Zinnia xylogenic cell cultures. As caspase inhibitors are
      closely associated with cell death inhibition in a variety of plant systems, this
      suggests that the altered TE formation results from suppression of PCD. The
      findings presented here are a first step towards the use of appropriate PCD
      signalling modulators or related molecular genetic strategies to improve the
      hydraulic properties of xylem vessels in favour of the quality and shelf life of
      plants or plant parts.

PMID- 20691059
TI  - Impact of central and peripheral TRPV1 and ROS levels on proinflammatory
      mediators and nociceptive behavior.
AB  - BACKGROUND: Transient receptor potential vanilloid 1 (TRPV1) channels are
      important membrane sensors on peripheral nerve endings and on supportive non
      neuronal synoviocytes in the knee joint. TRPV 1 ion channels respond with
      activation of calcium and sodium fluxes to pH, thermal, chemical, osmotic,
      mechanical and other stimuli abundant in inflamed joints. In the present study,
      the kaolin/carrageenan (k/c) induced knee joint arthritis model in rats, as well
      as primary and clonal human synoviocyte cultures were used to understand the
      reciprocal interactions between reactive nitroxidative species (ROS) and
      functional TRPV1 channels. ROS generation was monitored with ROS sensitive dyes
      using live cell imaging in vitro and in spinal tissue histology, as well as with
      measurement of ROS metabolites in culture media using HPLC. RESULTS: Functional
      responses in the experimental arthritis model, including increased nociceptive
      responses (thermal and mechanical hyperalgesia and allodynia), knee joint
      temperature reflecting local blood flow, and spinal cord ROS elevations were
      reduced by the ROS scavenger PBN after intraperitoneal pretreatment. Increases in
      TRPV1 and ROS, generated by synoviocytes in vitro, were reciprocally blocked by
      TRPV1 antagonists and the ROS scavenger. Further evidence is presented that
      synoviocyte responses to ROS and TRPV1 activation include increases in TNFalpha
      and COX-2, both measured as an indicator of the inflammation in vitro.
      CONCLUSIONS: The results demonstrate that contributions of ROS to pronociceptive
      responses and neurogenic inflammation are mediated both centrally and
      peripherally. Responses are mediated by TRPV1 locally in the knee joint by
      synoviocytes, as well as by ROS-induced sensitization in the spinal cord. These
      findings and those of others reported in the literature indicate reciprocal
      interactions between TRPV1 and ROS play critical roles in the pathological and
      nociceptive responses active during arthritic inflammation.

PMID- 20691060
TI  - Early impact of aortic wrapping on patients undergoing aortic valve replacement
      with mild to moderate ascending aorta dilatation.
AB  - BACKGROUND: The management of mild to moderate dilatation of the ascending aorta
      of less than 5 cm is controversial, particularly when concomitant surgical
      correction of aortic valve is required. We investigate the impact of a simple
      method of aorta reduction using Dacron graft wrapping during aortic valve
      replacement on the rest of the aorta. METHODS: We studied 14 patients who had
      ascending aorta dilatation of 4-5 cm before undergoing aortic wrapping during
      their aortic valve replacement and compared with their post-operative imaging
      within a month. RESULTS: The diameters of the ascending aorta wrapped with the
      Dacron graft were significantly reduced within 4 weeks after surgery from 44.7 +/
      2.6 to 33.6 +/- 3.9 mm (p < 0.001). This was associated with significant
      reduction in the diameter of rest of ascending aorta: coronary sinuses (from 37.9
      +/- 4.9 mm to 33.3 +/- 6.1 mm; p < 0.001), sinotubular junction (from 33.2 +/-
      4.7 mm to 30.6 +/- 4.4 mm, p = 0.02), and aortic arch (from 34.7 +/- 4.3 mm to
      32.6 +/- 4.1 mm, p = 0.03). CONCLUSIONS: Reduction of ascending aortic dilatation
      by wrapping with a Dacron graft in this preliminary study is associated with
      favourable early reversed aortic remodelling. This supports the hypothesis that
      correction of mild-moderate dilatation of the ascending aorta with Dacron
      wrapping at the time of aortic valve surgery may prevent the progression of the
      dilatation, although the long-term study on a larger population is needed to
      confirm its benefits.

PMID- 20691061
TI  - Decreased Hsp90 expression in infiltrative lobular carcinoma: an
      immunohistochemical study.
AB  - BACKGROUND: Elevated Hsp90 expression has been documented in breast ductal
      carcinomas, whereas decreased Hsp90 expression has been reported in precursor
      lobular lesions. This study aims to assess Hsp90 expression in infiltrative
      lobular carcinomas of the breast. METHODS: Tissue specimens were taken from 32
      patients with infiltrative lobular carcinoma. Immunohistochemical assessment of
      Hsp90 was performed both in the lesion and the adjacent normal breast ducts and
      lobules; the latter serving as control. Concerning Hsp90 assessment: i) the
      percentage of positive cells and ii) the intensity were separately analyzed.
      Subsequently, the Allred score was adopted and calculated. The intensity was
      treated as an ordinal variable-score (0: negative, low: 1, moderate: 2, high: 3).
      Statistical analysis followed. RESULTS: All infiltrative lobular carcinoma foci
      mainly presented with a positive cytoplasmic immunoreaction for Hsp90. Compared
      to the adjacent normal ducts and lobules, infiltrative lobular carcinoma
      exhibited a statistically significant decrease in Hsp90 expression, both in terms
      of Hsp90 positive cells (%) and Allred score (74.2 +/- 11.2 vs. 59.1 +/- 14.2 p =
      0.0001; 7.00 +/- 0.95 vs. 6.22 +/- 1.01, p = 0.007, Wilcoxon matched-pairs signed
      ranks test). Concerning the intensity of Hsp90 immunostaining only a marginal
      decrease was noted (2.16 +/- 0.68 vs. 1.84 +/- 0.63, p = 0.087, Wilcoxon matched
      pairs signed-ranks test). CONCLUSION: ILC lesions seem to exhibit decreased Hsp90
      expression, a finding contrary to what might have been expected, given that high
      Hsp90 expression is a trait of invasive ductal carcinomas.

PMID- 20691062
TI  - Mass spectrometry protein expression profiles in colorectal cancer tissue
      associated with clinico-pathological features of disease.
AB  - BACKGROUND: Studies of several tumour types have shown that expression profiling
      of cellular protein extracted from surgical tissue specimens by direct mass
      spectrometry analysis can accurately discriminate tumour from normal tissue and
      in some cases can sub-classify disease. We have evaluated the potential value of
      this approach to classify various clinico-pathological features in colorectal
      cancer by employing matrix-assisted laser desorption ionisation time of-flight
      mass spectrometry (MALDI-TOF MS). METHODS: Protein extracts from 31 tumour and 33
      normal mucosa specimens were purified, subjected to MALDI-Tof MS and then
      analysed using the 'GenePattern' suite of computational tools (Broad Institute,
      MIT, USA). Comparative Gene Marker Selection with either a t-test or a signal-to
      noise ratio (SNR) test statistic was used to identify and rank differentially
      expressed marker peaks. The k-nearest neighbours algorithm was used to build
      classification models either using separate training and test datasets or else by
      using an iterative, 'leave-one-out' cross-validation method. RESULTS: 73 protein
      peaks in the mass range 1800-16000Da were differentially expressed in tumour
      verses adjacent normal mucosa tissue (P < or = 0.01, false discovery rate < or =
      0.05). Unsupervised hierarchical cluster analysis classified most tumour and
      normal mucosa into distinct cluster groups. Supervised prediction correctly
      classified the tumour/normal mucosa status of specimens in an independent test
      spectra dataset with 100% sensitivity and specificity (95% confidence interval:
      67.9-99.2%). Supervised prediction using 'leave-one-out' cross validation
      algorithms for tumour spectra correctly classified 10/13 poorly differentiated
      and 16/18 well/moderately differentiated tumours (P = < 0.001; receiver-operator
      characteristics - ROC - error, 0.171); disease recurrence was correctly predicted
      in 5/6 cases and disease-free survival (median follow-up time, 25 months) was
      correctly predicted in 22/23 cases (P = < 0.001; ROC error, 0.105). A similar
      analysis of normal mucosa spectra correctly predicted 11/14 patients with, and
      15/19 patients without lymph node involvement (P = 0.001; ROC error, 0.212).
      CONCLUSIONS: Protein expression profiling of surgically resected CRC tissue
      extracts by MALDI-TOF MS has potential value in studies aimed at improved
      molecular classification of this disease. Further studies, with longer follow-up
      times and larger patient cohorts, that would permit independent validation of
      supervised classification models, would be required to confirm the predictive
      value of tumour spectra for disease recurrence/patient survival.

PMID- 20691063
TI  - What's "quickest and easiest?": parental decision making about school trip mode.
AB  - BACKGROUND: The potential benefits of active school travel (AST) are widely
      recognized, yet there is consistent evidence of a systematic decline in the use
      of active modes of transportation to school since the middle part of the 20th
      century. This study explored parental accounts of the school travel mode choice
      decision-making process. METHODS: Thirty-seven parents of children (17 who
      walked; 20 who were driven) from four elementary schools in Toronto, Canada
      participated in semi-structured interviews. The schools varied with respect to
      walkability of the built environment and socio-economic status. Thematic analysis
      of interview transcripts identified a two-stage decision-making process. RESULTS:
      An initial decision concerned the issue of escorting or chauffeuring a child
      to/from school. This decision appeared to be primarily influenced by concerns
      about traffic, the child's personal safety, and the child's maturity and
      cognitive ability regarding navigating his/her way to/from school safely.
      Following the escort decision, parents considered mode choice, typically
      selecting what they perceived to be the easiest and most convenient way to
      travel. The ascription of convenience to the various modes of transportation was
      influenced by perceptions of travel time and/or distance to/from school.
      Convenience became a particularly salient theme for parents who found it
      necessary to complete multi-activity trip chains. CONCLUSIONS: The school travel
      mode choice decision process is complex. Future research and practice should
      continue to address safety concerns that are typically the focus of active school
      transport initiatives while addressing more explicitly the behavioural cost of
      competing mode choices.

PMID- 20691064
TI  - The contribution of chronic diseases to the prevalence of dependence among older
      people in Latin America, China and India: a 10/66 Dementia Research Group
      population-based survey.
AB  - BACKGROUND: The number of older people is set to increase dramatically worldwide.
      Demographic changes are likely to result in the rise of age-related chronic
      diseases which largely contribute to years lived with a disability and future
      dependence. However dependence is much less studied although intrinsically linked
      to disability. We investigated the prevalence and correlates of dependence among
      older people from middle income countries. METHODS: A one-phase cross-sectional
      survey was carried out at 11 sites in seven countries (urban sites in Cuba,
      Venezuela, and Dominican Republic, urban and rural sites in Peru, Mexico, China
      and India). All those aged 65 years and over living in geographically defined
      catchment areas were eligible. In all, 15,022 interviews were completed with an
      informant interview for each participant. The full 10/66 Dementia Research Group
      survey protocol was applied, including ascertainment of depression, dementia,
      physical impairments and self-reported diagnoses. Dependence was interviewer
      rated based on a key informant's responses to a set of open-ended questions on
      the participant's needs for care. We estimated the prevalence of dependence and
      the independent contribution of underlying health conditions. Site-specific
      prevalence ratios were meta-analysed, and population attributable prevalence
      fractions (PAPF) calculated. RESULTS: The prevalence of dependence increased with
      age at all sites, with a tendency for the prevalence to be lower in men than in
      women. Age-standardised prevalence was lower in all sites than in the USA. Other
      than in rural China, dementia made the largest independent contribution to
      dependence, with a median PAPF of 34% (range 23%-59%). Other substantial
      contributors were limb impairment (9%, 1%-46%), stroke (8%, 2%-17%), and
      depression (8%, 1%-27%). CONCLUSION: The demographic and health transitions will
      lead to large and rapid increases in the numbers of dependent older people
      particularly in middle income countries (MIC). The prevention and control of
      chronic neurological and neuropsychiatric diseases and the development of long
      term care policies and plans should be urgent priorities.

PMID- 20691065
TI  - The atypical presence of the paternal mitochondrial DNA in somatic tissues of
      male and female individuals of the blue mussel species Mytilus galloprovincialis.
AB  - BACKGROUND: In animals mtDNA inheritance is maternal except in certain molluscan
      bivalve species which have a paternally inherited mitochondrial genome (genome M)
      along with the standard maternal one (genome F). Normally, the paternal genome
      occurs in the male gonad, but it can be often found, as a minority, in somatic
      tissues of males and females. This may happen in two ways. One is through "sperm
      mtDNA leakage" into somatic tissues, a deviation from the normal situation in
      which the sperm mtDNA vanishes in females or ends up exclusively in the germ line
      of males. The other is through "egg heteroplasmy", when the egg contains, in
      small quantities, the paternal genome in addition to maternal genome. FINDINGS:
      To test the two hypotheses, we compared the sequences of one of the most variable
      domains of the M molecule in a somatic tissue (foot) and in the sperm of ten male
      and in the foot of ten female individuals of M. galloprovincialis. Presence of
      the M genome was rarer in the foot of females than males. The M genome in the
      sperm and in the foot of males was identical. CONCLUSIONS: Given that the
      surveyed region differs from individual to individual, the identity of the M
      genome in the foot and the sperm of males supports strongly the hypothesis that,
      at least for the tissue examined, the presence of the M genome is due to sperm
      mtDNA leakage.

PMID- 20691066
TI  - 124I-HuCC49deltaCH2 for TAG-72 antigen-directed positron emission tomography
      (PET) imaging of LS174T colon adenocarcinoma tumor implants in xenograft mice:
      preliminary results.
AB  - BACKGROUND: 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) is
      widely used in diagnostic cancer imaging. However, the use of 18F-FDG in PET
      based imaging is limited by its specificity and sensitivity. In contrast, anti
      TAG (tumor associated glycoprotein)-72 monoclonal antibodies are highly specific
      for binding to a variety of adenocarcinomas, including colorectal cancer. The aim
      of this preliminary study was to evaluate a complimentary determining region
      (CDR)-grafted humanized CH2-domain-deleted anti-TAG-72 monoclonal antibody
      (HuCC49deltaCH2), radiolabeled with iodine-124 (124I), as an antigen-directed and
      cancer-specific targeting agent for PET-based imaging. METHODS: HuCC49deltaCH2
      was radiolabeled with 124I. Subcutaneous tumor implants of LS174T colon
      adenocarcinoma cells, which express TAG-72 antigen, were grown on athymic Nu/Nu
      nude mice as the xenograft model. Intravascular (i.v.) and intraperitoneal (i.p.)
      administration of 124I-HuCC49deltaCH2 was then evaluated in this xenograft mouse
      model at various time points from approximately 1 hour to 24 hours after
      injection using microPET imaging. This was compared to i.v. injection of 18F-FDG
      in the same xenograft mouse model using microPET imaging at 50 minutes after
      injection. RESULTS: At approximately 1 hour after i.v. injection, 124I
      HuCC49deltaCH2 was distributed within the systemic circulation, while at
      approximately 1 hour after i.p. injection, 124I-HuCC49deltaCH2 was distributed
      within the peritoneal cavity. At time points from 18 hours to 24 hours after i.v.
      and i.p. injection, 124I-HuCC49deltaCH2 demonstrated a significantly increased
      level of specific localization to LS174T tumor implants (p=0.001) when compared
      to the 1 hour images. In contrast, approximately 50 minutes after i.v. injection,
      18F-FDG failed to demonstrate any increased level of specific localization to a
      LS174T tumor implant, but showed the propensity toward more nonspecific uptake
      within the heart, Harderian glands of the bony orbits of the eyes, brown fat of
      the posterior neck, kidneys, and bladder. CONCLUSIONS: On microPET imaging, 124I
      HuCC49deltaCH2 demonstrates an increased level of specific localization to tumor
      implants of LS174T colon adenocarcinoma cells in the xenograft mouse model on
      delayed imaging, while 18F-FDG failed to demonstrate this. The antigen-directed
      and cancer-specific 124I-radiolabled anti-TAG-72 monoclonal antibody conjugate,
      124I-HuCC49deltaCH2, holds future potential for use in human clinical trials for
      preoperative, intraoperative, and postoperative PET-based imaging strategies,
      including fused-modality PET-based imaging platforms.

PMID- 20691067
TI  - Enhancing a sustainable healthy working life: design of a clustered randomized
      controlled trial.
AB  - BACKGROUND: To improve a sustainable healthy working life, we have developed the
      intervention 'Staying healthy at work', which endeavours to enhance work
      participation of employees aged 45 years and older by increasing their problem
      solving capacity and stimulating their awareness of their role and responsibility
      towards a healthy working life. This research study aims to evaluate the process
      and the effectiveness of the intervention compared with care as usual.
      METHODS/DESIGN: The study is a cluster-randomized controlled trial design
      (randomized at the supervisor level), with a 1-year follow-up. Workers aged 45
      years and older have been enrolled in the study. Workers in the intervention
      group are receiving the intervention 'Staying healthy at work'. The main focus of
      the intervention is to promote a healthy working life of ageing workers by: (1)
      changing workers awareness and behaviour, by emphasizing their own decisive role
      in attaining goals; (2) improving the supervisors' ability to support workers in
      taking the necessary action, by means of enhancing knowledge and competence; and
      (3) enhancing the use of the human resource professionals and the occupational
      health tools available within the organization. The supervisors in the
      intervention group have been trained how to present themselves as a source of
      support for the worker. Workers in the control group are receiving care as usual;
      supervisors in the control group have not participated in the training.
      Measurements have been taken at baseline and will be followed up at 3, 6 and 12
      months. The primary outcome measures are vitality, work ability and productivity.
      The secondary outcomes measures include fatigue, job strain, work attitude, self
      efficacy and work engagement. A process evaluation will be conducted at both the
      supervisor and the worker levels, and satisfaction with the content of the
      intervention will be assessed. DISCUSSION: The intervention 'Staying healthy at
      work' has the potential to provide evidence-based knowledge of an innovative
      method to promote a sustainable healthy working life in the older working
      population. The results of the study will be relevant for workers, employers,
      occupational health professionals and human resource professionals. TRIAL
      REGISTRATION: The trial is registered with the Dutch Trial Register under number
      NTR2270.

PMID- 20691068
TI  - A microsatellite-based analysis for the detection of selection on BTA1 and BTA20
      in northern Eurasian cattle (Bos taurus) populations.
AB  - BACKGROUND: Microsatellites surrounding functionally important candidate genes or
      quantitative trait loci have received attention as proxy measures of polymorphism
      level at the candidate loci themselves. In cattle, selection for economically
      important traits is a long-term strategy and it has been reported that
      microsatellites are linked to these important loci. METHODS: We have investigated
      the variation of seven microsatellites on BTA1 (Bos taurus autosome 1) and 16 on
      BTA20, using bovine populations of typical production types and horn status in
      northern Eurasia. Genetic variability of these loci and linkage disequilibrium
      among these loci were compared with those of 28 microsatellites on other bovine
      chromosomes. Four different tests were applied to detect molecular signatures of
      selection. RESULTS: No marked difference in locus variability was found between
      microsatellites on BTA1, BTA20 and the other chromosomes in terms of different
      diversity indices. Average D' values of pairwise syntenic markers (0.32 and 0.28
      across BTA 1 and BTA20 respectively) were significantly (P < 0.05) higher than
      for non-syntenic markers (0.15). The Ewens-Watterson test, the Beaumont and
      Nichol's modified frequentist test and the Bayesian FST-test indicated elevated
      or decreased genetic differentiation, at SOD1 and AGLA17 markers respectively,
      deviating significantly (P < 0.05) from neutral expectations. Furthermore, lnRV,
      lnRH and lnRtheta' statistics were used for the pairwise population comparison
      tests and were significantly less variable in one population relative to the
      other, providing additional evidence of selection signatures for two of the 51
      loci. Moreover, the three Finnish native populations showed evidence of
      subpopulation divergence at SOD1 and AGLA17. Our data also indicate significant
      intergenic linkage disequilibrium around the candidate loci and suggest that
      hitchhiking selection has played a role in shaping the pattern of observed
      linkage disequilibrium. CONCLUSION: Hitchhiking due to tight linkage with alleles
      at candidate genes, e.g. the POLL gene, is a possible explanation for this
      pattern. The potential impact of selective breeding by man on cattle populations
      is discussed in the context of selection effects. Our results also suggest that a
      practical approach to detect loci under selection is to simultaneously apply
      multiple neutrality tests based on different assumptions and estimations.

PMID- 20691069
TI  - Primary psoas abscess extending to thigh adductors: case report.
AB  - BACKGROUND: Psoas abscess is a rare condition consisting of pyomyositis of the
      psoas. The worldwide incidence was 12 cases per 100,000 per year in 1992, but the
      current incidence is unknown. Psoas abscess can descend along the psoas sheath
      and reach the inner upper third of the thigh, but only infrequently does it
      penetrate the sheath and involve the thigh adductors. Because of insidious
      clinical presentation, the diagnosis of psoas abscess is a challenge. Delayed
      diagnosis can result in poor prognosis. CASE PRESENTATION: A 45-year-old male
      with no significant past medical history presented with pain in the left thigh,
      and limitation of movement at the left hip and knee joint for one month.
      Ultrasound, CT, and MRI revealed a liquid mass in the left psoas. Percutaneous
      drainage of this mass yielded 300 ml pus from the psoas. After surgery, the
      patient reported relief of pain; however, ten days after removal of the drainage
      tube, the patient complained of persistent pain in his left thigh. CT revealed
      that the psoas abscess had extended inferiorly, and involved the entire set of
      adductors of the left thigh. Open surgical drainage was performed at the flank
      and at the thigh, yielding 350 ml of pus from the thigh. After open drainage and
      adequate antibiotic therapy, the patient made a good recovery. Follow-up CT
      confirmed complete resolution of the abscess. CONCLUSIONS: Large psoas abscess
      can penetrate the psoas sheath, and descend to thigh adductors even after
      percutaneous drainage. Appropriate treatment includes open surgical drainage
      along with antibiotic therapy.

PMID- 20691070
TI  - Transcriptome analysis of the oil-rich seed of the bioenergy crop Jatropha curcas
      L.
AB  - BACKGROUND: To date, oil-rich plants are the main source of biodiesel products.
      Because concerns have been voiced about the impact of oil-crop cultivation on the
      price of food commodities, the interest in oil plants not used for food
      production and amenable to cultivation on non-agricultural land has soared. As a
      non-food, drought-resistant and oil-rich crop, Jatropha curcas L. fulfils many of
      the requirements for biofuel production. RESULTS: We have generated 13,249
      expressed sequence tags (ESTs) from developing and germinating Jatropha seeds.
      This strategy allowed us to detect most known genes related to lipid synthesis
      and degradation. We have also identified ESTs coding for proteins that may be
      involved in the toxicity of Jatropha seeds. Another unexpected finding is the
      high number of ESTs containing transposable element-related sequences in the
      developing seed library (800) when contrasted with those found in the germinating
      seed library (80). CONCLUSIONS: The sequences generated in this work represent a
      considerable increase in the number of sequences deposited in public databases.
      These results can be used to produce genetically improved varieties of Jatropha
      with increased oil yields, different oil compositions and better agronomic
      characteristics.

PMID- 20691071
TI  - In Helicobacter pylori auto-inducer-2, but not LuxS/MccAB catalysed reverse
      transsulphuration, regulates motility through modulation of flagellar gene
      transcription.
AB  - BACKGROUND: LuxS may function as a metabolic enzyme or as the synthase of a
      quorum sensing signalling molecule, auto-inducer-2 (AI-2); hence, the mechanism
      underlying phenotypic changes upon luxS inactivation is not always clear. In
      Helicobacter pylori, we have recently shown that, rather than functioning in
      recycling methionine as in most bacteria, LuxS (along with newly-characterised
      MccA and MccB), synthesises cysteine via reverse transsulphuration. In this
      study, we investigated whether and how LuxS controls motility of H. pylori,
      specifically if it has its effects via luxS-required cysteine metabolism or via
      AI-2 synthesis only. RESULTS: We report that disruption of luxS renders H. pylori
      non-motile in soft agar and by microscopy, whereas disruption of mccAHp or mccBHp
      (other genes in the cysteine provision pathway) does not, implying that the lost
      phenotype is not due to disrupted cysteine provision. The motility defect of the
      DeltaluxSHp mutant was complemented genetically by luxSHp and also by addition of
      in vitro synthesised AI-2 or 4, 5-dihydroxy-2, 3-pentanedione (DPD, the precursor
      of AI-2). In contrast, exogenously added cysteine could not restore motility to
      the DeltaluxSHp mutant, confirming that AI-2 synthesis, but not the metabolic
      effect of LuxS was important. Microscopy showed reduced number and length of
      flagella in the DeltaluxSHp mutant. Immunoblotting identified decreased levels of
      FlaA and FlgE but not FlaB in the DeltaluxSHp mutant, and RT-PCR showed that the
      expression of flaA, flgE, motA, motB, flhA and fliI but not flaB was reduced.
      Addition of DPD but not cysteine to the DeltaluxSHp mutant restored flagellar
      gene transcription, and the number and length of flagella. CONCLUSIONS: Our data
      show that as well as being a metabolic enzyme, H. pylori LuxS has an alternative
      role in regulation of motility by modulating flagellar transcripts and flagellar
      biosynthesis through production of the signalling molecule AI-2.

PMID- 20691072
TI  - The Wnt/beta-catenin pathway regulates growth and maintenance of colonospheres.
AB  - BACKGROUND: Recent evidence suggests that epithelial cancers, including
      colorectal cancer are driven by a small sub-population of self-renewing, multi
      potent cells termed cancer stem cells (CSCs) which are thought to be responsible
      for recurrence of cancer. One of the characteristics of CSCs is their ability to
      form floating spheroids under anchorage-independent conditions in a serum-free
      defined media. The current investigation was undertaken to examine the role of
      Wnt/beta-catenin pathway in regulating the growth and maintenance of
      colonospheres. Human colon cancer cells HCT-116 (p53 wild type; K-ras mutant),
      HCT-116 (p53 null; K-ras mutant) and HT-29 (p53 mutant) were used. RESULTS:
      Colonospheres formed in vitro exhibited higher expression of colon CSCs markers
      LGR5, CD44, CD166 and Musashi-1 along with putative CSC marker EpCAM, compared to
      the corresponding parental cancer cells and also exhibit the ability to form
      spheroids under extreme limiting dilution, indicating the predominance of CSCs in
      colonospheres. Colonospheres formed by HCT-116 cells show over 80% of the cells
      to be CD44 positive, compared to <or= 1% in the corresponding parental cells.
      Additionally, colonospheres showed reduced membrane bound beta-catenin but had
      increased levels of total beta-catenin, cyclin-D1 and c-myc and down regulation
      of axin-1 and phosphorylated beta-catenin. Increased expression of beta-catenin
      was associated with a marked transcriptional activation of TCF/LEF. The latter
      was greatly decreased following down regulation of beta-catenin by the
      corresponding siRNA, leading to a marked reduction in CD44 positive cells as well
      as colonospheres formation. In contrast, upregulation of c-myc, a down-stream
      effector of TCF/LEF greatly augmented the formation of colonospheres. CONCLUSION:
      Our data suggest that colonospheres formed by colon cancer cell lines are highly
      enriched in CSCs and that Wnt/beta-catenin pathway plays a critical role in
      growth and maintenance of colonospheres.

PMID- 20691073
TI  - Translational bioinformatics in the cloud: an affordable alternative.
AB  - With the continued exponential expansion of publicly available genomic data and
      access to low-cost, high-throughput molecular technologies for profiling patient
      populations, computational technologies and informatics are becoming vital
      considerations in genomic medicine. Although cloud computing technology is being
      heralded as a key enabling technology for the future of genomic research,
      available case studies are limited to applications in the domain of high
      throughput sequence data analysis. The goal of this study was to evaluate the
      computational and economic characteristics of cloud computing in performing a
      large-scale data integration and analysis representative of research problems in
      genomic medicine. We find that the cloud-based analysis compares favorably in
      both performance and cost in comparison to a local computational cluster,
      suggesting that cloud computing technologies might be a viable resource for
      facilitating large-scale translational research in genomic medicine.

PMID- 20691074
TI  - Maca (L. meyenii) for improving sexual function: a systematic review.
AB  - BACKGROUND: Maca (Lepidium meyenii) is an Andean plant of the brassica (mustard)
      family. Preparations from maca root have been reported to improve sexual
      function. The aim of this review was to assess the clinical evidence for or
      against the effectiveness of the maca plant as a treatment for sexual
      dysfunction. METHODS: We searched 17 databases from their inception to April 2010
      and included all randomised clinical trials (RCTs) of any type of maca compared
      to a placebo for the treatment of healthy people or human patients with sexual
      dysfunction. The risk of bias for each study was assessed using Cochrane
      criteria, and statistical pooling of data was performed where possible. The
      selection of studies, data extraction, and validations were performed
      independently by two authors. Discrepancies were resolved through discussion by
      the two authors. RESULTS: Four RCTs met all the inclusion criteria. Two RCTs
      suggested a significant positive effect of maca on sexual dysfunction or sexual
      desire in healthy menopausal women or healthy adult men, respectively, while the
      other RCT failed to show any effects in healthy cyclists. The further RCT
      assessed the effects of maca in patients with erectile dysfunction using the
      International Index of Erectile Dysfunction-5 and showed significant effects.
      CONCLUSION: The results of our systematic review provide limited evidence for the
      effectiveness of maca in improving sexual function. However, the total number of
      trials, the total sample size, and the average methodological quality of the
      primary studies were too limited to draw firm conclusions. More rigorous studies
      are warranted.

PMID- 20691076
TI  - Comparative analysis of expressed sequence tags from three castes and two life
      stages of the termite Reticulitermes flavipes.
AB  - BACKGROUND: Termites (Isoptera) are eusocial insects whose colonies consist of
      morphologically and behaviorally specialized castes of sterile workers and
      soldiers, and reproductive alates. Previous studies on eusocial insects have
      indicated that caste differentiation and behavior are underlain by differential
      gene expression. Although much is known about gene expression in the honey bee,
      Apis mellifera, termites remain relatively understudied in this regard.
      Therefore, our objective was to assemble an expressed sequence tag (EST) data
      base for the eastern subterranean termite, Reticulitermes flavipes, for future
      gene expression studies. RESULTS: Soldier, worker, and alate caste and two larval
      cDNA libraries were constructed, and approximately 15,000 randomly chosen clones
      were sequenced to compile an EST data base. Putative gene functions were assigned
      based on a BLASTX Swissprot search. Categorical in silico expression patterns for
      each library were compared using the R-statistic. A significant proportion of the
      ESTs of each caste and life stages had no significant similarity to those in
      existing data bases. All cDNA libraries, including those of non-reproductive
      worker and soldier castes, contained sequences with putative reproductive
      functions. Genes that showed a potential expression bias among castes included a
      putative antibacterial humoral response and translation elongation protein in
      soldiers and a chemosensory protein in alates. CONCLUSIONS: We have expanded upon
      the available sequences for R. flavipes and utilized an in silico method to
      compare gene expression in different castes of an eusocial insect. The in silico
      analysis allowed us to identify several genes which may be differentially
      expressed and involved in caste differences. These include a gene overrepresented
      in the alate cDNA library with a predicted function of neurotransmitter secretion
      or cholesterol absorption and a gene predicted to be involved in protein
      biosynthesis and ligase activity that was overrepresented in the late larval
      stage cDNA library. The EST data base and analyses reported here will be a
      valuable resource for future studies on the genomics of R. flavipes and other
      termites.

PMID- 20691077
TI  - The early asthmatic response is associated with glycolysis, calcium binding and
      mitochondria activity as revealed by proteomic analysis in rats.
AB  - BACKGROUND: The inhalation of allergens by allergic asthmatics results in the
      early asthmatic response (EAR), which is characterized by acute airway
      obstruction beginning within a few minutes. The EAR is the earliest indicator of
      the pathological progression of allergic asthma. Because the molecular mechanism
      underlying the EAR is not fully defined, this study will contribute to a better
      understanding of asthma. METHODS: In order to gain insight into the molecular
      basis of the EAR, we examined changes in protein expression patterns in the lung
      tissue of asthmatic rats during the EAR using 2-DE/MS-based proteomic techniques.
      Bioinformatic analysis of the proteomic data was then performed using PPI Spider
      and KEGG Spider to investigate the underlying molecular mechanism. RESULTS: In
      total, 44 differentially expressed protein spots were detected in the 2-DE gels.
      Of these 44 protein spots, 42 corresponded to 36 unique proteins successfully
      identified using mass spectrometry. During subsequent bioinformatic analysis, the
      gene ontology classification, the protein-protein interaction networking and the
      biological pathway exploration demonstrated that the identified proteins were
      mainly involved in glycolysis, calcium binding and mitochondrial activity. Using
      western blot and semi-quantitative RT-PCR, we confirmed the changes in expression
      of five selected proteins, which further supports our proteomic and bioinformatic
      analyses. CONCLUSIONS: Our results reveal that the allergen-induced EAR in
      asthmatic rats is associated with glycolysis, calcium binding and mitochondrial
      activity, which could establish a functional network in which calcium binding may
      play a central role in promoting the progression of asthma.

PMID- 20691078
TI  - Chromosome 9p21.3 polymorphism in a Chinese Han population is associated with
      angiographic coronary plaque progression in non-diabetic but not in type 2
      diabetic patients.
AB  - BACKGROUND: We sought to explore the association of variant rs1333049 on
      chromosome 9p21.3 with coronary artery disease (CAD) and angiographic plaque
      progression in non-diabetic and type 2 diabetic patients. METHODS: Genotyping and
      quantitative coronary angiography (QCA) were performed in 2046 Chinese Han
      patients (1012 diabetic cases) undergoing coronary angiography; 430 of them
      received repeat angiographic studies at 1-year follow-up. RESULTS: CC genotype at
      rs1333049 on chromosome 9p21.3 was associated with CAD (unadjusted OR 1.524, p =
      0.001 and adjusted OR 1.859, p = 0.005, respectively). However, CC genotype had
      no magnified association with CAD in diabetic patients (OR 1.275, p = 0.150)
      compared with non-diabetic counterparts (OR 1.446, p = 0.020) after adjusting for
      conventional risk factors. During angiographic follow-up, non-diabetic patients
      (n = 280) had significant decrease in minimal lumen diameter and increase in
      percent diameter stenosis among the three genotypes (p = 0.005 and p = 0.038,
      respectively), demonstrating that CC or GC genotype carriers had a more severe
      plaque progression than GG genotype carriers. In patients with type 2 diabetes (n
      = 150), although plaque progression was more severe than that in non-diabetic
      counterparts, no relations existed between plaque progression and genotypes.
      Rs1333049 was an independent determinant of plaque progression for non-diabetic
      (OR 3.468, p = 0.004 and OR 4.339, p = 0.002 for GC and CC genotype,
      respectively) but not for diabetic patients (OR 0.529, p = 0.077 and 0R 0.878, p
      = 0.644 for GC and CC genotype, respectively). CONCLUSIONS: This study
      demonstrates a significant association of homozygous CC genotype of rs1333049 on
      chromosome 9p21.3 with CAD in Chinese Han population. Rs1333049 polymorphism is
      an independent determinant for coronary plaque progression in non-diabetic but
      not in type 2 diabetic patients.

PMID- 20691080
TI  - Development of recurrent facial palsy during plasmapheresis in Guillain-Barre
      syndrome: a case report.
AB  - INTRODUCTION: Guillain-Barre syndrome is an immune-mediated polyneuropathy that
      is routinely initially treated with either intravenous immunoglobulin or
      plasmapheresis. To the best of our knowledge, no association between
      plasmapheresis treatment and acute onset of facial neuropathy has been reported.
      CASE PRESENTATION: A 35-year-old Caucasian man with no significant prior medical
      history developed ascending motor weakness and laboratory findings consistent
      with a diagnosis of Guillain-Barre syndrome. Plasmapheresis was initiated. Acute
      facial palsy developed during the plasma exchange that subsequently resolved and
      then acutely recurred during the subsequent plasma exchange. CONCLUSION: To the
      best of our knowledge, no prior cases of acute facial palsy developing during
      plasmapheresis treatment are known. Although facial nerve involvement is common
      in typical Guillain-Barre syndrome, the temporal association with treatment, near
      complete resolution and later recurrence support the association. The possible
      mechanism of plasmapheresis-induced worsening of peripheral nerve function in
      Guillain-Barre syndrome is unknown.

PMID- 20691079
TI  - SLUG/SNAI2 and tumor necrosis factor generate breast cells with CD44+/CD24-
      phenotype.
AB  - BACKGROUND: Breast cancer cells with CD44+/CD24- cell surface marker expression
      profile are proposed as cancer stem cells (CSCs). Normal breast epithelial cells
      that are CD44+/CD24- express higher levels of stem/progenitor cell associated
      genes. We, amongst others, have shown that cancer cells that have undergone
      epithelial to mesenchymal transition (EMT) display the CD44+/CD24- phenotype.
      However, whether all genes that induce EMT confer the CD44+/CD24- phenotype is
      unknown. We hypothesized that only a subset of genes associated with EMT
      generates CD44+/CD24- cells. METHODS: MCF-10A breast epithelial cells, a
      subpopulation of which spontaneously acquire the CD44+/CD24- phenotype, were used
      to identify genes that are differentially expressed in CD44+/CD24- and CD44
      /CD24+ cells. Ingenuity pathway analysis was performed to identify signaling
      networks that linked differentially expressed genes. Two EMT-associated genes
      elevated in CD44+/CD24- cells, SLUG and Gli-2, were overexpressed in the CD44
      /CD24+ subpopulation of MCF-10A cells and MCF-7 cells, which are CD44-/CD24+.
      Flow cytometry and mammosphere assays were used to assess cell surface markers
      and stem cell-like properties, respectively. RESULTS: Two thousand thirty five
      genes were differentially expressed (p < 0.001, fold change >or= 2) between the
      CD44+/CD24- and CD44-/CD24+ subpopulations of MCF-10A. Thirty-two EMT-associated
      genes including SLUG, Gli-2, ZEB-1, and ZEB-2 were expressed at higher levels in
      CD44+/CD24- cells. These EMT-associated genes participate in signaling networks
      comprising TGFbeta, NF-kappaB, and human chorionic gonadotropin. Treatment with
      tumor necrosis factor (TNF), which induces NF-kappaB and represses E-cadherin, or
      overexpression of SLUG in CD44-/CD24+ MCF-10A cells, gave rise to a subpopulation
      of CD44+/CD24- cells. Overexpression of constitutively active p65 subunit of NF
      kappaB in MCF-10A resulted in a dramatic shift to the CD44+/CD24+ phenotype. SLUG
      overexpression in MCF-7 cells generated CD44+/CD24+ cells with enhanced
      mammosphere forming ability. In contrast, Gli-2 failed to alter CD44 and CD24
      expression. CONCLUSIONS: EMT-mediated generation of CD44+/CD24- or CD44+/CD24+
      cells depends on the genes that induce or are associated with EMT. Our studies
      reveal a role for TNF in altering the phenotype of breast CSC. Additionally, the
      CD44+/CD24+ phenotype, in the context of SLUG overexpression, can be associated
      with breast CSC "stemness" behavior based on mammosphere forming ability.

PMID- 20691081
TI  - Diagnostic efficiency of abattoir meat inspection service in Ethiopia to detect
      carcasses infected with Mycobacterium bovis: implications for public health.
AB  - BACKGROUND: Bovine Tuberculosis (BTB) is a widespread and endemic disease of
      cattle in Ethiopia posing a significant threat to public health. Regular
      surveillance by skin test, bacteriology and molecular methods is not feasible due
      to lack of resource. Thus, routine abattoir (RA) inspection will continue to play
      a key role for national surveillance. We evaluated efficiency of RA inspection
      for diagnosis of Mycobacterium bovis infection and discussed its public health
      implications in light of a high risk of human exposure. METHODS: The study was
      conducted in five abattoirs: Addis Ababa, Adama, Hawassa, Yabello and Melge-Wondo
      abattoirs. The efficiency of routine abattoir (RA) inspection was validated in
      comparison to detailed abattoir (DA) inspection, followed by culture and
      microscopy (CM) and region of difference (RD) deletion analysis. Diagnostic
      accuracies (with corresponding measures of statistical uncertainty) were
      determined by computing test property statistics (sensitivity and specificity)
      and likelihood estimations using web-based SISA diagnostic statistics software.
      Post-test probability of detecting TB infected carcasses was estimated using
      nomograms. Agreement between RA and DA inspections was measured using kappa
      statistics. The study was conducted and reported in accordance with standards for
      reporting of diagnostic accuracy (STARD) requirements. Both routine and detailed
      meat inspection protocols were performed on a subpopulation of 3322 cattle
      selected randomly from among 78,269 cattle slaughtered during the study period.
      Three hundred thirty seven carcasses identified through detailed meat inspection
      protocols were subjected to culture and microscopy; of the 337, a subset of 105
      specimens for culture and microscopy were subjected to further molecular testing.
      RESULTS: There was a substantial agreement between RA and DA inspections in Addis
      Ababa (Kappa = 0.7) and Melge-Wondo abattoirs (Kappa = 0.67). In Adama, Hawassa
      and Yabello abattoirs, the agreement was however poor (Kappa <or= 0.2). RA
      inspection was able to detect only 117 of the total 3322 carcasses inspected
      (3.5%). The sensitivity (Sn) and specificity (Sp) of RA inspection were 28.2%
      (95/337) [95%CI: 23.4-33.0] and 99.3% (2963/2985) [95%CI: 99.0-99.6],
      respectively, when DA inspection was considered as reference test. When culture
      and microscopy (CM) was considered as reference test, the Sn and Sp of RA were
      55.2% (58/105) [95%CI: 45.7-64.7] and 84.1% (195/232) [95%CI: 79.3-88.8]. RA
      inspection failed to detect 71.8% (242/337) and 44.8% (47/105) of TB infected
      carcasses as judged by DA inspection and CM, respectively. On the other hand, a
      much higher sensitivity of DA was obtained when CM and RD deletion analysis were
      considered as reference tests (96.3% (105/109) and 100.0% (24/24), respectively).
      CONCLUSIONS: The study results indicate that meat inspection protocols currently
      utilized in abattoirs are insufficient to detect the majority of TB lesions at
      the gross level. DA inspection protocols were demonstrated to improve the
      detection level by approximately 3-fold. The failure of current inspection
      techniques to detect approximately 70% of carcasses presented with grossly
      visible lesions of TB at the slaughter-plants indicates the magnitude of meat
      borne zoonotic TB as an on-going risk to public health. Standardization of
      abattoir inspection protocols (in line with international sanitary requirements),
      enhanced training and proficiency testing of meat inspections, and raising public
      awareness are recommended as essential and cost-effective interventions to
      improve meat inspection service in Ethiopia, with subsequent protection of
      consumers' health.

PMID- 20691082
TI  - HSP70: a promising target for laryngeal carcinoma radiaotherapy by inhibiting
      cleavage and degradation of nucleolin.
AB  - Previous studies have shown that heat shock proteins (HSPs) were upregulated in
      various types of tumors and were associated with histological grade, recurrence
      and metastasis of malignant tumors. In this study, we investigated whether heat
      shock protein 70 kDa (HSP70) was associated with histological grade of laryngeal
      squamous cell carcinomas (LSCC). We also determine the role of HSP70 in LSCC
      radiation resistance using a laryngeal carcinoma xenograft model by antisense
      HSP70 RNA technique. Immunohistochemistry data showed that HSP70 was detected in
      96% of LSCC tissues (48 out of 50). The expression level of HSP70 was
      significantly lower in early stage of LSCC than that in late stage (P = 0.015).
      Radiation treatment result showed that the volumes and weights of implantation
      tumors in the group injected with antisense HSP70 oligos were significantly
      reduced comparing to the group injected with random oligos(p < 0.05). In
      addition, cleavage and degradation of tumor nucleolin in antisense HSP70 oligos
      injection group was significantly higher than that in random oligos injection
      group. Our result suggested that HSP70 may play a role in LSCC radiotherapy
      resistance by inhibiting cleavage and degradation of nucleolin.

PMID- 20691083
TI  - Scope of nanotechnology in ovarian cancer therapeutics.
AB  - This review describes the use of polymer micelle nanotechnology based
      chemotherapies for ovarian cancer. While various chemotherapeutic agents can be
      utilized to improve the survival rate of patients with ovarian cancer, their
      distribution throughout the entire body results in high normal organ toxicity.
      Polymer micelle nanotechnology aims to improve the therapeutic efficacy of anti
      cancer drugs while minimizing the side effects. Herein, different types of
      polymer micelle technology based nanotherapies such as PLGA, polymerosomes, acid
      cleavable, thermosensitive, pH sensitive, and cross-linked micelles are
      introduced and structural differences are explained. Additionally, production
      methods, stability, sustainability, drug incorporation and drug release profiles
      of various polymer micelle based nanoformulations are discussed. An important
      feature of polymer micelle nanotechnology is the small size (10-100 nm) of
      particles which improves circulation and enables superior accumulation of the
      therapeutic drugs at the tumor sites. This review provides a comprehensive
      evaluation of different types of polymer micelles and their implications in
      ovarian cancer therapeutics.

PMID- 20691084
TI  - Osteoblastoma-like Osteosarcoma of the Cuboid: A Case Report.
AB  - Osteosarcoma most commonly arises in the long bones of the skeleton, and rarely
      develops in the bones of the foot. We describe a patient who presented with left
      foot pain, whose radiographic evaluation revealed a lytic destructive mass in the
      cuboid bone. A biopsy showed an osteoblastoma-like variant of osteosarcoma and
      the patient was treated with preoperative chemotherapy and amputation.
      Osteosarcoma of the foot is uncommon and the literature reveals that it is often
      associated with a delay in diagnosis.

PMID- 20691086
TI  - A cause of circulatory collapse that should be considered following trauma.
AB  - Management of poly-trauma patients presenting to the emergency room is usually a
      challenging and formidable task. Two of the common problems seen in those
      patients are shock and neurological dysfunction. A huge differential for post
      traumatic circulatory collapse exist and timely identification of the etiology is
      of utmost importance to avoid complications. In this report we are describing 2
      cases presenting with circulatory collapse following trauma. The first case was a
      29 year old female who presented after a motor vehicle accident fully conscious
      with severe hypotension and bradycardia. The second case presented with severe
      hemodynamic instability after falling at home. Physical examination of both
      patients revealed weakness in all 4 limbs and CT cervical spine revealed complete
      anterior sublaxation of C5 over C6 cervical vertebrae in the first case and
      partial sublaxation of C5 over C6 cervical vertebrae in the second case
      confirming that spinal cord injury is the likely cause for these hemodynamic
      alterations. A high index of suspicion for spinal cord injuries is therefore
      mandatory when managing a trauma patient presenting with quadriparesis and
      hemodynamic instability that is otherwise unexplained especially when the ensuing
      hypotension is associated with bradycardia instead of reflex tachycardia.
      Awareness of this cause of circulatory collapse is particularly important in the
      unconscious patient where eliciting sensory and motor deficits looking for spinal
      cord injury is not always feasible. Both patients were transferred to the
      intensive care unit and were maintained on epinephrine till becoming
      hemodynamically stable. The report aims to sensitize readers to this cause of
      post-traumatic circulatory collapse.

PMID- 20691085
TI  - The ascorbic acid content of tomato fruits is associated with the expression of
      genes involved in pectin degradation.
AB  - BACKGROUND: High levels of ascorbic acid (AsA) in tomato fruits provide health
      benefits for humans and also play an important role in several aspects of plant
      life. Although AsA metabolism has been characterized in detail, the genetic
      mechanisms controlling AsA accumulation in tomatoes are poorly understood. The
      transcriptional control of AsA levels in fruits can be investigated by combining
      the advanced genetic and genomic resources currently available for tomato. A
      comparative transcriptomic analysis of fruit tissues was carried out on an
      introgression line containing a QTL promoting AsA accumulation in the fruit,
      using a parental cultivar with lower AsA levels as a reference. RESULTS:
      Introgression line IL 12-4 (S. pennellii in a S. lycopersicum background) was
      selected for transcriptomic analysis because it maintained differences in AsA
      levels compared to the parental genotypes M82 and S. pennellii over three
      consecutive trials. Comparative microarray analysis of IL 12-4 and M82 fruits
      over a 2-year period allowed 253 differentially-expressed genes to be identified,
      suggesting that AsA accumulation in IL 12-4 may be caused by a combination of
      increased metabolic flux and reduced utilization of AsA. In particular, the
      upregulation of a pectinesterase and two polygalacturonases suggests that AsA
      accumulation in IL12-4 fruit is mainly achieved by increasing flux through the L
      galactonic acid pathway, which is driven by pectin degradation and may be
      triggered by ethylene. CONCLUSIONS: Based on functional annotation, gene ontology
      classification and hierarchical clustering, a subset of the 253 differentially
      expressed transcripts was used to develop a model to explain the higher AsA
      content in IL 12-4 fruits in terms of metabolic flux, precursor availability,
      demand for antioxidants, abundance of reactive oxygen species and ethylene
      signaling.

PMID- 20691087
TI  - Chemical-genetic profile analysis of five inhibitory compounds in yeast.
AB  - BACKGROUND: Chemical-genetic profiling of inhibitory compounds can lead to
      identification of their modes of action. These profiles can help elucidate the
      complex interactions between small bioactive compounds and the cell machinery,
      and explain putative gene function(s). RESULTS: Colony size reduction was used to
      investigate the chemical-genetic profile of cycloheximide, 3-amino-1,2,4
      triazole, paromomycin, streptomycin and neomycin in the yeast Saccharomyces
      cerevisiae. These compounds target the process of protein biosynthesis. More than
      70,000 strains were analyzed from the array of gene deletion mutant yeast
      strains. As expected, the overall profiles of the tested compounds were similar,
      with deletions for genes involved in protein biosynthesis being the major
      category followed by metabolism. This implies that novel genes involved in
      protein biosynthesis could be identified from these profiles. Further
      investigations were carried out to assess the activity of three profiled genes in
      the process of protein biosynthesis using relative fitness of double mutants and
      other genetic assays. CONCLUSION: Chemical-genetic profiles provide insight into
      the molecular mechanism(s) of the examined compounds by elucidating their
      potential primary and secondary cellular target sites. Our follow-up
      investigations into the activity of three profiled genes in the process of
      protein biosynthesis provided further evidence concerning the usefulness of
      chemical-genetic analyses for annotating gene functions. We termed these genes
      TAE2, TAE3 and TAE4 for translation associated elements 2-4.

PMID- 20691088
TI  - Measuring gene expression divergence: the distance to keep.
AB  - BACKGROUND: Gene expression divergence is a phenotypic trait reflecting evolution
      of gene regulation and characterizing dissimilarity between species and between
      cells and tissues within the same species. Several distance measures, such as
      Euclidean and correlation-based distances have been proposed for measuring
      expression divergence. RESULTS: We show that different distance measures identify
      different trends in gene expression patterns. When comparing orthologous genes in
      eight rat and human tissues, the Euclidean distance identified genes uniformly
      expressed in all tissues near the expression background as genes with the most
      conserved expression pattern. In contrast, correlation-based distance and
      generalized-average distance identified genes with concerted changes among
      homologous tissues as those most conserved. On the other hand, correlation-based
      distance, Euclidean distance and generalized-average distance highlight quite
      well the relatively high similarity of gene expression patterns in homologous
      tissues between species, compared to non-homologous tissues within species.
      CONCLUSIONS: Different trends exist in the high-dimensional numeric data, and to
      highlight a particular trend an appropriate distance measure needs to be chosen.
      The choice of the distance measure for measuring expression divergence can be
      dictated by the expression patterns that are of interest in a particular study.

PMID- 20691089
TI  - Acyclovir inhibition of IDO to decrease Tregs as a glioblastoma treatment
      adjunct.
AB  - Regulatory T cells, Tregs, are a subset of lymphocytes that have
      immunosuppressive attributes. They are elevated in blood of glioblastoma patients
      and within this tumor's tissue itself. Indoleamine 2,3-dioxygenase, IDO, converts
      tryptophan to kynurenine. IDO activity enhances Treg formation by pathways that
      are unknown. Experimentally, inhibition of IDO decreases Treg function and number
      in rodents. The common anti-viral agent acyclovir inhibits IDO. Acyclovir may
      thereby decrease Treg function in glioblastoma. If it can be confirmed that Treg
      counts are elevated in glioblastoma patients' tumor tissue, and if we can
      document acyclovir's lowering of tissue Treg counts by a small trial of acyclovir
      in pre-operative glioblastoma patients, a trial of acyclovir effect on survival
      should be done given the current poor prognosis of glioblastoma and the well
      established safety and low side effect burden of acyclovir.

PMID- 20691090
TI  - Analysis of intra-genomic GC content homogeneity within prokaryotes.
AB  - BACKGROUND: Bacterial genomes possess varying GC content (total guanines (Gs) and
      cytosines (Cs) per total of the four bases within the genome) but within a given
      genome, GC content can vary locally along the chromosome, with some regions
      significantly more or less GC rich than on average. We have examined how the GC
      content varies within microbial genomes to assess whether this property can be
      associated with certain biological functions related to the organism's
      environment and phylogeny. We utilize a new quantity GCVAR, the intra-genomic GC
      content variability with respect to the average GC content of the total genome. A
      low GCVAR indicates intra-genomic GC homogeneity and high GCVAR heterogeneity.
      RESULTS: The regression analyses indicated that GCVAR was significantly
      associated with domain (i.e. archaea or bacteria), phylum, and oxygen
      requirement. GCVAR was significantly higher among anaerobes than both aerobic and
      facultative microbes. Although an association has previously been found between
      mean genomic GC content and oxygen requirement, our analysis suggests that no
      such association exits when phylogenetic bias is accounted for. A significant
      association between GCVAR and mean GC content was also found but appears to be
      non-linear and varies greatly among phyla. CONCLUSIONS: Our findings show that
      GCVAR is linked with oxygen requirement, while mean genomic GC content is not. We
      therefore suggest that GCVAR should be used as a complement to mean GC content.

PMID- 20691091
TI  - Survival dimensionality reduction (SDR): development and clinical application of
      an innovative approach to detect epistasis in presence of right-censored data.
AB  - BACKGROUND: Epistasis is recognized as a fundamental part of the genetic
      architecture of individuals. Several computational approaches have been developed
      to model gene-gene interactions in case-control studies, however, none of them is
      suitable for time-dependent analysis. Herein we introduce the Survival
      Dimensionality Reduction (SDR) algorithm, a non-parametric method specifically
      designed to detect epistasis in lifetime datasets. RESULTS: The algorithm
      requires neither specification about the underlying survival distribution nor
      about the underlying interaction model and proved satisfactorily powerful to
      detect a set of causative genes in synthetic epistatic lifetime datasets with a
      limited number of samples and high degree of right-censorship (up to 70%). The
      SDR method was then applied to a series of 386 Dutch patients with active
      rheumatoid arthritis that were treated with anti-TNF biological agents. Among a
      set of 39 candidate genes, none of which showed a detectable marginal effect on
      anti-TNF responses, the SDR algorithm did find that the rs1801274 SNP in the Fc
      gamma RIIa gene and the rs10954213 SNP in the IRF5 gene non-linearly interact to
      predict clinical remission after anti-TNF biologicals. CONCLUSIONS: Simulation
      studies and application in a real-world setting support the capability of the SDR
      algorithm to model epistatic interactions in candidate-genes studies in presence
      of right-censored data. AVAILABILITY:
      http://sourceforge.net/projects/sdrproject/.

PMID- 20691092
TI  - Differences in prevalence of self-reported musculoskeletal symptoms among
      computer and non-computer users in a Nigerian population: a cross-sectional
      study.
AB  - BACKGROUND: Literature abounds on the prevalent nature of Self Reported
      Musculoskeletal Symptoms (SRMS) among computer users, but studies that actually
      compared this with non computer users are meagre thereby reducing the strength of
      the evidence. This study compared the prevalence of SRMS between computer and non
      computer users and assessed the risk factors associated with SRMS. METHODS: A
      total of 472 participants comprising equal numbers of age and sex matched
      computer and non computer users were assessed for the presence of SRMS.
      Information concerning musculoskeletal symptoms and discomforts from the neck,
      shoulders, upper back, elbows, wrists/hands, low back, hips/thighs, knees and
      ankles/feet were obtained using the Standardized Nordic questionnaire. RESULTS:
      The prevalence of SRMS was significantly higher in the computer users than the
      non computer users both over the past 7 days (chi2 = 39.11, p = 0.001) and during
      the past 12 month durations (chi2 = 53.56, p = 0.001). The odds of reporting
      musculoskeletal symptoms was least for participants above the age of 40 years (OR
      = 0.42, 95% CI = 0.31-0.64 over the past 7 days and OR = 0.61; 95% CI = 0.47-0.77
      during the past 12 months) and also reduced in female participants. Increasing
      daily hours and accumulated years of computer use and tasks of data processing
      and designs/graphics significantly (p < 0.05) increased the risk of reporting
      musculoskeletal symptoms. Over the past 7 day duration, the neck (33.9%) and low
      back (11.4%) had highest prevalence of SRMS for the computer and non computer
      users respectively. CONCLUSION: The prevalence of SRMS was significantly higher
      in the computer users than the non computer users and younger age, being male,
      working longer hours daily, increasing years of computer use, data entry tasks
      and computer designs/graphics were the significant risk factors for reporting
      musculoskeletal symptoms among the computer users. Computer use may explain the
      increase in prevalence of SRMS among the computer users.

PMID- 20691093
TI  - Dynamic splinting in wrist extension following distal radius fractures.
AB  - BACKGROUND: Wrist flexion contracture is a common pathology which presents
      secondary to distal radius fractures. Joint stability, restoration and early
      mobilization are frequently achieved through surgical treatment after such an
      injury. The purpose of this retrospective study was to evaluate the initial
      effect of dynamic splinting on wrist extension (active range of motion), in both
      surgical and non-surgical patients following distal radius fractures. METHODS:
      Records were obtained from 133 patients who were treated with a Wrist Extension
      Dynasplint (WED) following distal radius fractures, between May 2007 and May
      2009. Forty-two of these patients received surgical treatment for their
      fractures. This study specifically examined the initial usage of the WED as a
      home therapy. The retrospective analysis included categorization of patients who
      received the WED exclusively vs. patients who received WED treatment with
      concurrent hand therapy; surgical categorization included surgical patients vs.
      nonsurgical patients. RESULTS: There was a significant improvement in maximal
      active range of motion (AROM) for all patients (P < 0.0001) after a mean duration
      of 3.9 weeks of dynamic splinting. Patients showed a mean 62% increase in active
      extension. There was not a significant difference between patients who had
      received surgical treatment for the fracture vs. nonsurgical. CONCLUSION: This
      dynamic splinting modality contributed 138 to 185 hours of stretching at the end
      range of motion for these patients in their first month following fracture. This
      unique regime is considered directly responsible for significant gains in AROM.

PMID- 20691094
TI  - Epidural cement leakage through pedicle violation after balloon kyphoplasty
      causing paraparesis in osteoporotic vertebral compression fractures - a report of
      two cases.
AB  - Kyphoplasty is advantageous over vertebroplasty in terms of better kyphosis
      correction and diminished risk of cement extravasations. Literature described
      cement leakage causing neurological injury mainly after vertebroplasty procedure;
      only a few case reports show cement leakage with kyphoplasty without neurological
      injury or proper cause of leakage. We present a report two cases of osteoporotic
      vertebral compression fracture treated with kyphoplasty and developed cement
      leakage causing significant neurological injury. In both cases CT scan was the
      diagnostic tool to identify cause of cement leakage. CT scan exhibited violation
      of medial pedicle wall causing cement leakage in the spinal canal. Both patients
      displayed clinical improvement after decompression surgery with or without
      instrumentation. Retrospectively looking at stored fluoroscopic images, we found
      that improper position of trocar in AP and lateral view simultaneously while
      taking entry caused pedicle wall violation. We suggest not to cross medial
      pedicle wall in AP image throughout the entire procedure and keeping the trocar
      in the center of pedicle in lateral image would be the most important precaution
      to prevent such complication. Our case reports adds the neurological
      complications with kyphoplasty procedure and suggested that along with other
      precautions described in the literature, entry with trocar along the entire
      procedure keeping the oval shape of pedicle in mind (under C-arm) will probably
      help to prevent such complications.

PMID- 20691095
TI  - Ferret badger rabies origin and its revisited importance as potential source of
      rabies transmission in Southeast China.
AB  - BACKGROUND: The frequent occurrence of ferret badger-associated human rabies
      cases in southeast China highlights the lack of laboratory-based surveillance and
      urges revisiting the potential importance of this animal in rabies transmission.
      To determine if the ferret badgers actually contribute to human and dog rabies
      cases, and the possible origin of the ferret badger-associated rabies in the
      region, an active rabies survey was conducted to determine the frequency of
      rabies infection and seroprevalence in dogs and ferret badgers. METHODS: A
      retrospective survey on rabies epidemics was performed in Zhejiang, Jiangxi and
      Anhui provinces in southeast China. The brain tissues from ferret badgers and
      dogs were assayed by fluorescent antibody test. Rabies virus was isolated and
      sequenced for phylogenetic analysis. The sera from ferret badgers and dogs were
      titrated using rabies virus neutralizing antibodies (VNA) test. RESULTS: The
      ferret badgers presented a higher percentage of rabies seroconversion than dogs
      did in the endemic region, reaching a maximum of 95% in the collected samples.
      Nine ferret badger-associated rabies viruses were isolated, sequenced, and were
      phylogenetically clustered as a separate group. Nucleotide sequence revealed 99.4
      99.8% homology within the ferret badger isolates, and 83-89% homology to the dog
      isolates in the nucleoprotein and glycoprotein genes in the same rabies endemic
      regions. CONCLUSIONS: Our data suggest ferret badger-associated rabies has likely
      formed as an independent enzootic originating from dogs during the long-term
      rabies infestation in southeast China. The eventual role of FB rabies in public
      health remains unclear. However, management of ferret badger bites, rabies
      awareness and control in the related regions should be an immediate need.

PMID- 20691096
TI  - Distributed probing of chromatin structure in vivo reveals pervasive chromatin
      accessibility for expressed and non-expressed genes during tissue differentiation
      in C. elegans.
AB  - BACKGROUND: Tissue differentiation is accompanied by genome-wide changes in the
      underlying chromatin structure and dynamics, or epigenome. By controlling when,
      where, and what regulatory factors have access to the underlying genomic DNA, the
      epigenome influences the cell's transcriptome and ultimately its function.
      Existing genomic methods for analyzing cell-type-specific changes in chromatin
      generally involve two elements: (i) a source for purified cells (or nuclei) of
      distinct types, and (ii) a specific treatment that partitions or degrades
      chromatin by activity or structural features. For many cell types of great
      interest, such assays are limited by our inability to isolate the relevant cell
      populations in an organism or complex tissue containing an intertwined mixture of
      other cells. This limitation has confined available knowledge of chromatin
      dynamics to a narrow range of biological systems (cell types that can be
      sorted/separated/dissected in large numbers and tissue culture models) or to
      amalgamations of diverse cell types (tissue chunks, whole organisms). RESULTS:
      Transgene-driven expression of DNA/chromatin modifying enzymes provides one
      opportunity to query chromatin structures in expression-defined cell subsets. In
      this work we combine in vivo expression of a bacterial DNA adenine
      methyltransferase (DAM) with high throughput sequencing to sample tissue-specific
      chromatin accessibility on a genome-wide scale. We have applied the method
      (DALEC: Direct Asymmetric Ligation End Capture) towards mapping a cell-type
      specific view of genome accessibility as a function of differentiated state.
      Taking advantage of C. elegans strains expressing the DAM enzyme in diverse
      tissues (body wall muscle, gut, and hypodermis), our efforts yield a genome-wide
      dataset measuring chromatin accessibility at each of 538,000 DAM target sites in
      the C. elegans (diploid) genome. CONCLUSIONS: Validating the DALEC mapping
      results, we observe a strong association between observed coverage by nucleosomes
      and low DAM accessibility. Strikingly, we observed no extended regions of
      inaccessible chromatin for any of the tissues examined. These results are
      consistent with "local choreography" models in which differential gene expression
      is driven by intricate local rearrangements of chromatin structure rather than
      gross impenetrability of large chromosomal regions.

PMID- 20691097
TI  - Barriers to the acceptance of electronic medical records by physicians from
      systematic review to taxonomy and interventions.
AB  - BACKGROUND: The main objective of this research is to identify, categorize, and
      analyze barriers perceived by physicians to the adoption of Electronic Medical
      Records (EMRs) in order to provide implementers with beneficial intervention
      options. METHODS: A systematic literature review, based on research papers from
      1998 to 2009, concerning barriers to the acceptance of EMRs by physicians was
      conducted. Four databases, "Science", "EBSCO", "PubMed" and "The Cochrane
      Library", were used in the literature search. Studies were included in the
      analysis if they reported on physicians' perceived barriers to implementing and
      using electronic medical records. Electronic medical records are defined as
      computerized medical information systems that collect, store and display patient
      information. RESULTS: The study includes twenty-two articles that have considered
      barriers to EMR as perceived by physicians. Eight main categories of barriers,
      including a total of 31 sub-categories, were identified. These eight categories
      are: A) Financial, B) Technical, C) Time, D) Psychological, E) Social, F) Legal,
      G) Organizational, and H) Change Process. All these categories are interrelated
      with each other. In particular, Categories G (Organizational) and H (Change
      Process) seem to be mediating factors on other barriers. By adopting a change
      management perspective, we develop some barrier-related interventions that could
      overcome the identified barriers. CONCLUSIONS: Despite the positive effects of
      EMR usage in medical practices, the adoption rate of such systems is still low
      and meets resistance from physicians. This systematic review reveals that
      physicians may face a range of barriers when they approach EMR implementation. We
      conclude that the process of EMR implementation should be treated as a change
      project, and led by implementers or change managers, in medical practices. The
      quality of change management plays an important role in the success of EMR
      implementation. The barriers and suggested interventions highlighted in this
      study are intended to act as a reference for implementers of Electronic Medical
      Records. A careful diagnosis of the specific situation is required before
      relevant interventions can be determined.

PMID- 20691099
TI  - In vitro evaluation of marine-microorganism extracts for anti-viral activity.
AB  - Viral-induced infectious diseases represent a major health threat and their
      control remains an unachieved goal, due in part to the limited availability of
      effective anti-viral drugs and measures. The use of natural products in drug
      manufacturing is an ancient and well-established practice. Marine organisms are
      known producers of pharmacological and anti-viral agents. In this study, a total
      of 20 extracts from marine microorganisms were evaluated for their antiviral
      activity. These extracts were tested against two mammalian viruses, herpes
      simplex virus (HSV-1) and vesicular stomatitis virus (VSV), using Vero cells as
      the cell culture system, and two marine virus counterparts, channel catfish virus
      (CCV) and snakehead rhabdovirus (SHRV), in their respective cell cultures (CCO
      and EPC). Evaluation of these extracts demonstrated that some possess antiviral
      potential. In sum, extracts 162M(4), 258M(1), 298M(4), 313(2), 331M(2), 367M(1)
      and 397(1) appear to be effective broad-spectrum antivirals with potential uses
      as prophylactic agents to prevent infection, as evident by their highly
      inhibitive effects against both virus types. Extract 313(2) shows the most
      potential in that it showed significantly high inhibition across all tested
      viruses. The samples tested in this study were crude extracts; therefore the
      development of antiviral application of the few potential extracts is dependent
      on future studies focused on the isolation of the active elements contained in
      these extracts.

PMID- 20691098
TI  - Possible use of ail and foxA polymorphisms for detecting pathogenic Yersinia
      enterocolitica.
AB  - BACKGROUND: Yersinia enterocolitica is an enteric pathogen that invades the
      intestinal mucosa and proliferates within the lymphoid follicles (Peyer's
      patches). The attachment invasion locus (ail) mediates invasion by Y.
      enterocolitica and confers an invasive phenotype upon non-invasive E. coli; ail
      is the primary virulence factor of Y. enterocolitica. The ferrioxamine receptor
      (foxA) located on the Y. enterocolitica chromosome, together with its transport
      protein, transports a siderophore specific for ferric ion. Currently, ail is the
      primary target gene for nucleic acid detection of pathogenic Y. enterocolitica.
      RESULTS: The genes ail and foxA in 271 pathogenic and 27 non-pathogenic Y.
      enterocolitica strains isolated from China and 10 reference strains were
      sequenced, aligned, compared to the ail and foxA sequences of Yersinia
      enterocolitica subsp. enterocolitica 8081 (Genbank: NC_008800), and analyzed for
      sequence polymorphism. The ail from the 282 strains showed 3 sequence patterns:
      277 strains of serotypes O:3, O:9 and O:5, 27 with identical nucleic acid
      sequences formed pattern A1; 4 strains of serotype 1B/O:8 with identical nucleic
      acid sequences formed pattern A2; and one Chinese isolate 2/O:9 formed pattern
      A3. In the primary coding region of the foxA ORF (Genebank: X60447 nt 433-1866;
      nt 28 to 1,461 in the ORF), the sequences formed 3 groups and were further
      divided into 8 sequence patterns. CONCLUSION: The ail and foxA loci of pathogenic
      Y. enterocolitica have been analyzed. The ail sequence was highly conserved among
      the same serotype strains from different sources; and foxA was highly conserved
      among the pathogenic strains, although there was some sequence diversity. Fewer
      strains were used from outside China, which is a limitation of the study.

PMID- 20691100
TI  - A small solitary non-parasitic hepatic cyst causing an intra-hepatic bile duct
      stricture: a case report.
AB  - INTRODUCTION: We report an unusual presentation of a small hepatic cyst causing
      cholangitis. CASE PRESENTATION: A 70-year-old Asian man was hospitalized for
      aggravated chronic pain in the right upper portion of his abdomen. Fever
      developed after admission. Laboratory tests revealed elevated hepatobiliary
      enzymes, inflammatory markers and carbohydrate antigen 19-9 without
      hyperbilirubinemia. Ultrasound and computed tomography demonstrated dilatation of
      the left intra-hepatic bile ducts. Endoscopic retrograde cholangiopancreatography
      showed that the right intra-hepatic bile ducts were normally filled with contrast
      medium, but the left intra-hepatic bile ducts were not seen in the confluence. A
      left hepatectomy was performed because a hidden malignancy could not be excluded.
      The surgical findings showed no tumor around the bile duct but rather a 2 cm cyst
      in segment four of Couinaud's category of the liver around the hilum. The
      pathology report was a solitary non-parasitic hepatic cyst compressing the bile
      duct. CONCLUSION: A very small solitary hepatic cyst might cause hepatic duct
      stricture if it is located near the hepatic hilum, and should be considered in
      the differential diagnosis of a hepatic duct stricture.

PMID- 20691101
TI  - Expression breadth and expression abundance behave differently in correlations
      with evolutionary rates.
AB  - BACKGROUND: One of the main objectives of the molecular evolution and
      evolutionary systems biology field is to reveal the underlying principles that
      dictate protein evolutionary rates. Several studies argue that expression
      abundance is the most critical component in determining the rate of evolution,
      especially in unicellular organisms. However, the expression breadth also needs
      to be considered for multicellular organisms. RESULTS: In the present paper, we
      analyzed the relationship between the two expression variables and rates using
      two different genome-scale expression datasets, microarrays and ESTs. A
      significant positive correlation between the expression abundance (EA) and
      expression breadth (EB) was revealed by Kendall's rank correlation tests. A novel
      random shuffling approach was applied for EA and EB to compare the correlation
      coefficients obtained from real data sets to those estimated based on random
      chance. A novel method called a Fixed Group Analysis (FGA) was designed and
      applied to investigate the correlations between expression variables and rates
      when one of the two expression variables was evenly fixed. CONCLUSIONS: In
      conclusion, all of these analyses and tests consistently showed that the breadth
      rather than the abundance of gene expression is tightly linked with the
      evolutionary rate in multicellular organisms.

PMID- 20691102
TI  - Na+-stimulated ATPase of alkaliphilic halotolerant cyanobacterium Aphanothece
      halophytica translocates Na+ into proteoliposomes via Na+ uniport mechanism.
AB  - BACKGROUND: When cells are exposed to high salinity conditions, they develop a
      mechanism to extrude excess Na+ from cells to maintain the cytoplasmic Na+
      concentration. Until now, the ATPase involved in Na+ transport in cyanobacteria
      has not been characterized. Here, the characterization of ATPase and its role in
      Na+ transport of alkaliphilic halotolerant Aphanothece halophytica were
      investigated to understand the survival mechanism of A. halophytica under high
      salinity conditions. RESULTS: The purified enzyme catalyzed the hydrolysis of ATP
      in the presence of Na+ but not K+, Li+ and Ca2+. The apparent Km values for Na+
      and ATP were 2.0 and 1.2 mM, respectively. The enzyme is likely the F1F0-ATPase
      based on the usual subunit pattern and the protection against N,N'
      dicyclohexylcarbodiimide inhibition of ATPase activity by Na+ in a pH-dependent
      manner. Proteoliposomes reconstituted with the purified enzyme could take up Na+
      upon the addition of ATP. The apparent Km values for this uptake were 3.3 and 0.5
      mM for Na+ and ATP, respectively. The mechanism of Na+ transport mediated by Na+
      stimulated ATPase in A. halophytica was revealed. Using acridine orange as a
      probe, alkalization of the lumen of proteoliposomes reconstituted with Na+
      stimulated ATPase was observed upon the addition of ATP with Na+ but not with K+,
      Li+ and Ca2+. The Na+- and ATP-dependent alkalization of the proteoliposome lumen
      was stimulated by carbonyl cyanide m - chlorophenylhydrazone (CCCP) but was
      inhibited by a permeant anion nitrate. The proteoliposomes showed both ATPase
      activity and ATP-dependent Na+ uptake activity. The uptake of Na+ was enhanced by
      CCCP and nitrate. On the other hand, both CCCP and nitrate were shown to
      dissipate the preformed electric potential generated by Na+-stimulated ATPase of
      the proteoliposomes. CONCLUSION: The data demonstrate that Na+-stimulated ATPase
      from A. halophytica, a likely member of F-type ATPase, functions as an
      electrogenic Na+ pump which transports only Na+ upon hydrolysis of ATP. A
      secondary event, Na+- and ATP-dependent H+ efflux from proteoliposomes, is driven
      by the electric potential generated by Na+-stimulated ATPase.

PMID- 20691103
TI  - Expression of the apoptosis-related genes BCL-2 and BAD in human breast carcinoma
      and their associated relationship with chemosensitivity.
AB  - OBJECTIVE: To evaluate the expression of BCL-2 and BAD genes in tissues of breast
      carcinoma and investigate the relationship between the expression of BCL-2 and
      BAD in breast cancer cells with chemosensitivity. METHODS: Immunohistochemical
      technique was used to detect the expression of BCL-2, BAD in 10 normal breast
      tissues, 10 breast fibroadenoma tissues, 40 youth human breast carcinoma tissues,
      40 menopause human breast carcinoma tissues. And to detect the expression of ER,
      PR in 80 human breast carcinoma tissues. 20 Surgical samples of breast cancer,
      diagnosed by pathology, were obtained from The First Affiliated Hospital of
      Chongqing Medical University. The cancer sample cells were cultured separately in
      the incubator at 37 degrees C, 5% CO2 in vitro. The rate of inhibition of cancer
      cells in 4 kinds of anticancer drugs-- Epirubicin Adriamycin (EADM),5
      Fluorouracil (5-Fu), Navelbine(NVB) and Diaminedichloroplatinum (DDP), were
      assayed by MTT method. RESULTS: The expression of BCL-2, BAD genes in young human
      breast carcinoma tissues were lower than that in menopause human breast carcinoma
      tissues (P < 0.05). There was a negative correlation between the positive
      expression rate of BCL-2 and histologic grade or the lymph node metastasis (P <
      0.05). There was a positive correlation between the expression rates of BCL-2 and
      of ER, PR (P < 0.05). The expression of BAD had no relationship with the
      expression of ER, PR, histologic grade and the lymph node metastasis(P = NS).
      Sensitivity rates of 20 breast cancer cells in 0.1 x PPC within 48 h in vitro
      were 30% EADM,20% 5-Fu,45% NVB and 25% DDP. Respectively, the rate of inhibition
      of EADM,5- Fu, NVB and DDP were significantly higher in the BCL-2 negative cancer
      cells than in the BCL-2 positive cancer cells. A negative correlation was found
      between expression of BCL-2 and chemosensitivity for all the 4 anticancer drugs.
      The inhibition rates of EADM and NVB were significantly lower in the BAD negative
      cancer cells than in the BAD positive cancer cells. A positive correlation was
      found between expression of BAD and chemosensitivity for Epirubicin. CONCLUSION:
      The expression of BCL-2 and BAD can be used as prognosis factors of breast
      cancer. Detection of the BCL-2 protein expression level, particularly, combined
      with the detection of the expression of BCL-2 and BAD as well as ER and PR were
      helpful in confirming the prognosis of breast carcinoma. The combined detection
      of BCL-2 and BAD may be markers for predicting the responses to anticancer drugs.

PMID- 20691104
TI  - Effects of larval growth condition and water availability on desiccation
      resistance and its physiological basis in adult Anopheles gambiae sensu stricto.
AB  - BACKGROUND: Natural populations of the malaria mosquito Anopheles gambiae s.s.
      are exposed to large seasonal and daily fluctuations in relative humidity and
      temperature, which makes coping with drought a crucial aspect of their ecology.
      METHODS: To better understand natural variation in desiccation resistance in this
      species, the effects of variation in larval food availability and access to water
      as an adult on subsequent phenotypic quality and desiccation resistance of adult
      females of the Mopti chromosomal form were tested experimentally. RESULTS: It was
      found that, under normal conditions, larval food availability and adult access to
      water had only small direct effects on female wet mass, dry mass, and water,
      glycogen and body lipid contents corrected for body size. In contrast, when
      females subsequently faced a strong desiccation challenge, larval food
      availability and adult access to water had strong carry-over effects on most
      measured physiological and metabolic parameters, and affected female survival.
      Glycogen and water content were the most used physiological reserves in relative
      terms, but their usage significantly depended on female phenotypic quality. Adult
      access to water significantly influenced the use of water and body lipid
      reserves, which subsequently affected desiccation resistance. CONCLUSIONS: These
      results demonstrate the importance of growth conditions and water availability on
      adult physiological status and subsequent resistance to desiccation.

PMID- 20691105
TI  - Intraoperative blood loss during different stages of scoliosis surgery: A
      prospective study.
AB  - BACKGROUND: There are a number of reasons for intraoperative blood loss during
      scoliosis surgery based on the type of approach, type of disease, osteopenia, and
      patient blood profile. However, no studies have investigated bleeding patterns
      according to the stage of the operation. The objective of this prospective study
      was to identify intraoperative bleeding patterns in different stages of scoliosis
      surgery. METHODS: We prospectively analyzed the estimated blood loss (EBL) and
      operation time over four stages of scoliosis surgery in 44 patients. The patients
      were divided into three groups: adolescent idiopathic (group 1), spastic
      neuromuscular (group 2) and paralytic neuromuscular (group 3). The per-level EBL
      and operation times of the groups were compared on a stage-by-stage basis. The
      bone marrow density (BMD) of each patient was also obtained, and the relationship
      between per-level EBL and BMD was compared using regression analysis. RESULTS:
      Per-level operation time was similar across all groups during surgical stage (p >
      0.05). Per-level EBL was also similar during the dissection and bone-grafting
      states (p > 0.05). However, during the screw insertion stage, the per-level EBL
      was significantly higher in groups 2 and 3 compared to group 1 (p < 0.05). In the
      correction stage, per-level EBL was highest in group 3 (followed in order by
      groups 2 and 1) (p < 0.05). Preoperative BMD indicated that group 3 had the
      lowest bone quality, followed by groups 2 and 1 (in order), but the preoperative
      blood indices were similar in all groups. The differences in bleeding patterns in
      the screw insertion and correction stages were attributed to the poor bone
      quality of groups 2 and 3. Group 3 had the lowest bone quality, which caused
      loosening of the bone-screw interface during the correction stage and led to more
      bleeding. Patients with a T-score less than -2.5 showed a risk for high per-level
      EBL that was nine times higher than those with scores greater than -2.5 (p =
      0.003). CONCLUSIONS: We investigated the blood loss patterns during different
      stages of scoliosis surgery. Patients with poor BMD showed a risk of blood loss
      nine times higher than those with good BMD.

PMID- 20691106
TI  - Different mutation patterns of Plasmodium falciparum among patients in Jimma
      University Hospital, Ethiopia.
AB  - BACKGROUND: The emergence of drug resistance is a major problem in malaria
      control. Combination of molecular genotyping and characterization of mutations or
      single nucleotide polymorphisms (SNPs) correlated with drug resistance can
      provide information for subsequent surveillance of existing and developing drug
      resistance patterns. The introduction of artemether/lumefantrine (AL) as first
      line treatment, never used before in Ethiopia, allowed the collection of baseline
      data of molecular polymorphisms before a selection due to AL could occur. METHOD:
      97 patients with uncomplicated falciparum malaria were recruited from April to
      June 2006 and treated with either AL, quinine (Q) or atovaquone/proguanil (AP) in
      Jimma University Hospital, Ethiopia. Mutations or SNPs associated with resistance
      to these drugs were analysed by RFLP (pfdhfr, pfmdr1) and sequencing of the
      target genes (pfcytb, pfserca ). RESULTS: SNPs previously reported to be
      associated with resistance to the study drugs were identified in recrudescent and
      treatment sensitive isolates. A total of seven recrudescences were obtained. The
      pfmdr1 N86Y mutation was found in 84.5% of isolates. The triple mutation
      51I,59R,108N of the pfdhfr gene occured in high frequency (83.3%) but no pfcytb
      mutation was detected. Sequencing showed a variety of previously described and
      new mutations in the pfserca gene. CONCLUSION: The prevalence of mutations was in
      accordance with the expected patterns considering recent drug regimens. The broad
      introduction of AL and the cessation of former drug regimens might probably
      change the current distribution of polymorphisms, possibly leading to decreased
      sensitivity to AL in future. Continuous surveillance of molecular patterns in
      this region is, therefore, recommended.

PMID- 20691107
TI  - Comparing interfacial dynamics in protein-protein complexes: an elastic network
      approach.
AB  - BACKGROUND: The transient, or permanent, association of proteins to form
      organized complexes is one of the most common mechanisms of regulation of
      biological processes. Systematic physico-chemical studies of the binding
      interfaces have previously shown that a key mechanism for the
      formation/stabilization of dimers is the steric and chemical complementarity of
      the two semi-interfaces. The role of the fluctuation dynamics at the interface of
      the interacting subunits, although expectedly important, proved more elusive to
      characterize. The aim of the present computational study is to gain insight into
      salient dynamics-based aspects of protein-protein interfaces. RESULTS: The
      interface dynamics was characterized by means of an elastic network model for 22
      representative dimers covering three main interface types. The three groups
      gather dimers sharing the same interface but with good (type I) or poor (type II)
      similarity of the overall fold, or dimers sharing only one of the semi-interfaces
      (type III). The set comprises obligate dimers, which are complexes for which no
      structural representative of the free form(s) is available. Considerations were
      accordingly limited to bound and unbound forms of the monomeric subunits of the
      dimers. We proceeded by first computing the mobility of amino acids at the
      interface of the bound forms and compare it with the mobility of (i) other
      surface amino acids (ii) interface amino acids in the unbound forms. In both
      cases different dynamic patterns were observed across interface types and
      depending on whether the interface belongs to an obligate or non-obligate
      complex. CONCLUSIONS: The comparative investigation indicated that the mobility
      of amino acids at the dimeric interface is generally lower than for other amino
      acids at the protein surface. The change in interfacial mobility upon removing
      "in silico" the partner monomer (unbound form) was next found to be correlated
      with the interface type, size and obligate nature of the complex. In particular,
      going from the unbound to the bound forms, the interfacial mobility is noticeably
      reduced for dimers with type I interfaces, while it is largely unchanged for type
      II ones. The results suggest that these structurally- and biologically-different
      types of interfaces are stabilized by different balancing mechanisms between
      enthalpy and conformational entropy.

PMID- 20691108
TI  - A qualitative study of the promotion of exclusive breastfeeding by health
      professionals in Niamey, Niger.
AB  - BACKGROUND: The practice of exclusive breastfeeding depends on various factors
      related to both mothers and their environment, including the services delivered
      by health professionals. It is known that support and counseling by health
      professionals can improve rates, early initiation and total duration of
      breastfeeding, particularly exclusive breastfeeding. Mothers' decisions are
      influenced by health professionals' advice. However, in Niger the practice of
      exclusive breastfeeding is almost non-existent.The purpose of this exploratory
      study, of which some results are presented here, was to document health
      professionals' attitudes and practices with regard to exclusive breastfeeding
      promotion in hospital settings in the urban community of Niamey, Niger. METHODS:
      Fieldwork was conducted in Niamey, Niger. A qualitative approach was employed.
      Health professionals' practices were observed in a sample of frontline public
      healthcare facilities. RESULTS: The field observation results presented here
      indicate that exclusive breastfeeding is not promoted in healthcare facilities
      because the health professionals do not encourage it and their practices are
      inappropriate. Some still have limited knowledge or are misinformed about this
      practice or do not believe in it. They do not systematically discuss exclusive
      breastfeeding with mothers, or they mention it only briefly and without giving
      any explanation. Worse still, some encourage the use of breast milk substitutes,
      which are frequently promoted in healthcare facilities. Thus mothers often
      receive contradictory messages. CONCLUSION: The results suggest the need to train
      or retrain health professionals with regard to exclusive breastfeeding, and
      regularly supervise their activities.

PMID- 20691109
TI  - Evaluation of high-resolution microarray platforms for genomic profiling of bone
      tumours.
AB  - BACKGROUND: Several high-density oligonucleotide microarray platforms are
      available for genome-wide single nucleotide polymorphism (SNP) detection and
      microarray-based comparative genomic hybridisation (array CGH), which may be used
      to detect copy number aberrations in human tumours. As part of the EuroBoNeT
      network of excellence for research on bone tumours (eurobonet.eu), we have
      evaluated four different commercial high-resolution microarray platforms in order
      to identify the most appropriate technology for mapping DNA copy number
      aberrations in such tumours. FINDINGS: DNA from two different cytogenetically
      well-characterized bone sarcoma cell lines, representing a simple and a complex
      karyotype, respectively, was tested in duplicate on four high-resolution
      microarray platforms; Affymetrix Genome-Wide Human SNP Array 6.0, Agilent Human
      Genome CGH 244A, Illumina HumanExon510s-duo and Nimblegen HG18 CGH 385 k WG
      tiling v1.0. The data was analysed using the platform-specific analysis software,
      as well as a platform-independent analysis algorithm. DNA copy number was
      measured at six specific chromosomes or chromosomal regions, and compared with
      the expected ratio based on available cytogenetic information. All platforms
      performed well in terms of reproducibility and were able to delimit and score
      small amplifications and deletions at similar resolution, but Agilent microarrays
      showed better linearity and dynamic range. The platform-specific analysis
      software provided with each platform identified in general correct copy numbers,
      whereas using a platform-independent analysis algorithm, correct copy numbers
      were determined mainly for Agilent and Affymetrix microarrays. CONCLUSIONS: All
      platforms performed reasonably well, but Agilent microarrays showed better
      dynamic range, and like Affymetrix microarrays performed well with the platform
      independent analysis software, implying more robust data. Bone tumours like
      osteosarcomas are heterogeneous tumours with complex karyotypes that may be
      difficult to interpret, and it is of importance to be able to well separate the
      copy number levels and detect copy number changes in subpopulations. Taking all
      this into consideration, the Agilent and Affymetrix microarray platforms were
      found to be a better choice for mapping DNA copy numbers in bone tumours, the
      latter having the advantage of also providing heterozygosity information.

PMID- 20691110
TI  - Molecular characterization of partial fusion gene and C-terminus extension length
      of haemagglutinin-neuraminidase gene of recently isolated Newcastle disease virus
      isolates in Malaysia.
AB  - BACKGROUND: Newcastle disease (ND), caused by Newcastle disease virus (NDV), is a
      highly contagious disease of birds and has been one of the major causes of
      economic losses in the poultry industry. Despite routine vaccination programs,
      sporadic cases have occasionally occurred in the country and remain a constant
      threat to commercial poultry. Hence, the present study was aimed to characterize
      NDV isolates obtained from clinical cases in various locations of Malaysia
      between 2004 and 2007 based on sequence and phylogenetic analysis of partial F
      gene and C-terminus extension length of HN gene. RESULTS: The coding region of
      eleven NDV isolates fusion (F) gene and carboxyl terminal region of
      haemagglutinin-neuraminidase (HN) gene including extensions were amplified by
      reverse transcriptase PCR and directly sequenced. All the isolates have shown to
      have non-synonymous to synonymous base substitution rate ranging between 0.081 -
      0.264 demonstrating presence of negative selection. Analysis based on F gene
      showed the characterized isolates possess three different types of protease
      cleavage site motifs; namely 112RRQKRF117, 112RRRKRF117 and 112GRQGRL117 and
      appear to show maximum identities with isolates in the region such as
      cockatoo/14698/90 (Indonesia), Ch/2000 (China), local isolate AF2240 indicating
      the high similarity of isolates circulating in the South East Asian countries.
      Meanwhile, one of the isolates resembles commonly used lentogenic vaccine
      strains. On further characterization of the HN gene, Malaysian isolates had C
      terminus extensions of 0, 6 and 11 amino acids. Analysis of the phylogenetic tree
      revealed that the existence of three genetic groups; namely, genotype II, VII and
      VIII. CONCLUSIONS: The study concluded that the occurrence of three types of NDV
      genotypes and presence of varied carboxyl terminus extension lengths among
      Malaysian isolates incriminated for sporadic cases.

PMID- 20691111
TI  - Self-medication with antibiotics in rural population in Greece: a cross-sectional
      multicenter study.
AB  - BACKGROUND: Self-medication is an important driver of antimicrobial overuse as
      well as a worldwide problem. The aim of the present study was to estimate the use
      of antibiotics, without medical prescription, in a sample of rural population
      presenting in primary care in southern Greece. METHODS: The study included data
      from 1,139 randomly selected adults (545 men/594 women, mean age +/- SD: 56.2 +/-
      19.8 years), who visited the 6 rural Health Centres of southern Greece, between
      November 2009 and January 2010. The eligible participants were sought out on a
      one-to-one basis and asked to answer an anonymous questionnaire. RESULTS: Use of
      antibiotics within the past 12 months was reported by 888 participants (77.9%).
      508 individuals (44.6%) reported that they had received antibiotics without
      medical prescription at least one time. The major source of self-medication was
      the pharmacy without prescription (76.2%). The antibiotics most frequently used
      for self-medication were amoxicillin (18.3%), amoxicillin/clavulanic acid
      (15.4%), cefaclor (9.7%), cefuroxim (7.9%), cefprozil (4.7%) and ciprofloxacin
      (2.3%). Fever (41.2%), common cold (32.0%) and sore throat (20.6%) were the most
      frequent indications for the use of self-medicated antibiotics. CONCLUSION: In
      Greece, despite the open and rapid access to primary care services, it appears
      that a high proportion of rural adult population use antibiotics without medical
      prescription preferably for fever and common cold.

PMID- 20691112
TI  - Leukocyte oxygen radical production determines disease severity in the recurrent
      Guillain-Barre syndrome.
AB  - BACKGROUND: The recurrent Guillain-Barre syndrome (RGBS) is characterized by at
      least two GBS episodes with intervening remission. In a previous study of
      monophasic GBS, we reported that the magnitude of oxygen radical production
      ("respiratory burst") in peripheral blood leukocytes was inversely correlated to
      disease severity. The present study sought to establish a similar correlation in
      patients with RGBS. METHODS: Oxygen radical production in leukocytes was induced
      by formyl-Met-Leu-Phe (fMLF), Trp-Lys-Tyr-Met-Val-Met-NH2 (WKYMVM), or phorbol
      myristate acetate (PMA) and assessed by quantifying superoxide anion formed by
      the leukocyte NADPH oxidase. RESULTS: Disease severity, assessed using the MRC
      score, was negatively correlated to superoxide anion production triggered by fMLF
      or WKYMVM (p = 0.001 and 0.002, respectively; n = 10). Superoxide anion
      production also was significantly lower in RGBS patients with incomplete recovery
      after stimulation with fMLF (p = 0.004) or WKYMVM (p = 0.003). CONCLUSION: We
      conclude that a lower respiratory burst in leukocytes is strongly associated with
      a severe course of RGBS.

PMID- 20691113
TI  - Aorto-venous fistula between an abdominal aortic aneurysm and an aberrant renal
      vein: a case report.
AB  - INTRODUCTION: The potential complications of an abdominal aortic aneurysm include
      rupture, compression of surrounding structures, thrombo-embolic events and
      fistula. The most common site of arterio-venous fistula is the inferior vena
      cava. Fistula involving a renal vein is particularly uncommon. CASE PRESENTATION:
      This report describes a 54-year-old Caucasian woman who was admitted to the
      emergency department with fatigue, severe dyspnea and bilateral lower limb edema.
      In the first instance this anamnesis suggested possible heart failure. In fact,
      our patient presented with multi-organ system failure due to a fistula between an
      infra-renal aortic aneurysm and an aberrant retro-aortic renal vein. CONCLUSIONS:
      To our knowledge, this is the first report of a woman with a fistula between an
      infra-renal aortic aneurysm and an aberrant retro-aortic left renal vein. Aorto
      venous fistulas may be asymptomatic or may present with symptoms characteristic
      of arterio-venous shunting and/or aneurysm rupture. This type of fistula is a
      rare cause of heart failure. Clinical examination and imaging are essential for
      detection.

PMID- 20691114
TI  - Relationship between spine osteoarthritis, bone mineral density and bone turn
      over markers in post menopausal women.
AB  - BACKGROUND: Several studies have observed an inverse relationship between
      osteoporosis and spinal osteoarthritis, the latter being considered as possibly
      delaying the development of osteoporosis. The aim of this study was to determine
      the association between individual radiographic features of spine degeneration,
      bone mineral density (BMD) and bone-turn over markers. METHODS: It was a cross
      sectional study of 277 post menopausal women. BMD of all patients was assessed at
      the spine and hip using dual-energy X-ray absorptiometry. Lateral spinal
      radiographs were evaluated for features of disc degeneration. Each vertebral
      level from L1/2 to L4/5 was assessed for the presence and severity of osteophytes
      and disc space narrowing (DSN). For Bone turn-over markers, we assessed serum
      osteocalcin and C-terminal cross-linking telopeptide of type I collagen (CTX).
      Linear regressions and partial correlation were used respectively to determine
      the association between each of disc degeneration features, BMD, and both CTX and
      osteocalcin. RESULTS: Mean age of patients was 58.7 +/- 7.7 years. Eighty four
      patients (31.2%) were osteoporotic and 88.44% had spine osteoarthritis. At all
      measured sites, there was an increase in BMD with increasing severity of disc
      narrowing while there was no association between severity of osteophytes and BMD.
      After adjustment for age and BMI, there was a significant negative correlation
      between CTX and DSN. However, no significant correlation was found between CTX
      and osteophytes and between osteocalcin and both osteophytes or DSN. CONCLUSION:
      In post menopausal women the severity of disc narrowing, but not osteophytes, is
      associated with a generalized increase in BMD and a decreased rate of bone
      resorption. These results are consistent with the hypothesis that osteoarthritis,
      through DSN, has a protective effect against bone loss, mediated by a lower rate
      of bone resorption. However, spine BMD is not a relevant surrogate marker for the
      assessment of osteoporosis in the spine in patients with osteoarthritis and
      debate as to the relationship between OA and OP is still open because of the
      contradictory data in the literature.

PMID- 20691115
TI  - Age-period-cohort modelling of non-Hodgkin's lymphoma incidence in a French
      region: a period effect compatible with an environmental exposure.
AB  - BACKGROUND: The incidence of non-Hodgkin's lymphoma (NHL) has risen steadily
      during the last few decades in all geographic regions covered by cancer
      registration for reasons that remain unknown. The aims of this study were to
      assess the relative contributions of age, period and cohort effects to NHL
      incidence patterns and therefore to provide clues to explain the increasing
      incidence. METHODS: Population and NHL incidence data were provided for the Doubs
      region (France) during the 1980-2005 period. NHL counts and person-years were
      tabulated into one-year classes by age (from 20 to 89) and calendar time period.
      Age-period-cohort models with parametric smooth functions (natural splines) were
      fitted to the data by assuming a Poisson distribution for the observed number of
      NHL cases. RESULTS: The age-standardised incidence rate increased from 4.7 in
      1980 to 11.9 per 100,000 person-years at risk in 1992 (corresponding to a 2.5
      fold increase) and stabilised afterwards (11.1 per 100,000 in 2005). Age effects
      showed a steadily increasing slope up to the age of 80 and levelled off for older
      ages. Large period curvature effects, both adjusted for cohort effects and non
      adjusted (p < 10-4 and p < 10-5, respectively), showed departure from linear
      periodic trends; period effects jumped markedly in 1983 and stabilised in 1992
      after a 2.4-fold increase (compared to the 1980 period). In both the age-period
      cohort model and the age-cohort model, cohort curvature effects were not
      statistically significant (p = 0.46 and p = 0.08, respectively). CONCLUSIONS: The
      increased NHL incidence in the Doubs region is mostly dependent on factors
      associated with age and calendar periods instead of cohorts. We found evidence
      for a levelling off in both incidence rates and period effects beginning in 1992.
      It is unlikely that the changes in classification (which occurred after 1995) and
      the improvements of diagnostic accuracy could largely account for the 1983-1992
      period-effect increase, giving way to an increased exposure to widely distributed
      risk factors including persistent organic pollutants and pesticides. Continued
      NHL incidence and careful analysis of period effects are of utmost importance to
      elucidate the enigmatic epidemiology of NHL.

PMID- 20691116
TI  - Chronic cough associated with Crohn's disease.
AB  - A 62-year-old man presented with chronic dry cough. He was known to have Crohn's
      disease which was in remission. A plain chest radiograph demonstrated bilateral
      apical infiltrates. A HRCT of the chest showed normal proximal airways. Stenosis
      of medium size airways was present with post-stenotic dilation. These dilated
      peripheral bronchi appeared fluid filled. Patchy areas of consolidation were seen
      as well. These changes were thought to be due to Crohn's disease involving the
      lungs and responded well to treatment with cortico-steroids. We report this
      uncommon radiological association with Crohn's disease.

PMID- 20691117
TI  - Hospital employees' theoretical knowledge on what to do in an in-hospital cardiac
      arrest.
AB  - BACKGROUND: Guidelines recommend that all health care professionals should be
      able to perform cardiopulmonary resuscitation (CPR), including the use of an
      automated external defibrillator. Theoretical knowledge of CPR is then
      necessary.The aim of this study was to investigate how much theoretical knowledge
      in CPR would increase among all categories of health care professionals lacking
      training in CPR, in an intervention hospital, after a systematic standardised
      training. Their results were compared with the staff at a control hospital with
      an ongoing annual CPR training programme. METHODS: Health care professionals at
      two hospitals, with a total of 3144 employees, answered a multiple-choice
      questionnaire before and after training in CPR. Bootstrapped chi-square tests and
      Fisher's exact test were used for the statistical analyses. RESULTS: In the
      intervention hospital, physicians had the highest knowledge pre-test, but other
      health care professionals including nurses and assistant nurses reached a
      relatively high level post-test. Improvement was inversely related to the level
      of previous knowledge and was thus most marked among other health care
      professionals and least marked among physicians.The staff at the control hospital
      had a significantly higher level of knowledge pre-test than the intervention
      hospital, whereas the opposite was found post-test. CONCLUSIONS: Overall
      theoretical knowledge increased after systematic standardised training in CPR.
      The increase was more pronounced for those without previous training and for
      those staff categories with the least medical education.

PMID- 20691118
TI  - Artemisone effective against murine cerebral malaria.
AB  - BACKGROUND: Artemisinins are the newest class of drug approved for malaria
      treatment. Due to their unique mechanism of action, rapid effect on Plasmodium,
      and high efficacy in vivo, artemisinins have become essential components of
      malaria treatment. Administration of artemisinin derivatives in combination with
      other anti-plasmodials has become the first-line treatment for uncomplicated
      falciparum malaria. However, their efficiency in cases of cerebral malaria (CM)
      remains to be determined. METHODS: The efficacy of several artemisinin
      derivatives for treatment of experimental CM was evaluated in ICR or C57BL/6 mice
      infected by Plasmodium berghei ANKA. Both mouse strains serve as murine models
      for CM. RESULTS: Artemisone was the most efficient drug tested, and could prevent
      death even when administered at relatively late stages of cerebral pathogenesis.
      No parasite resistance to artemisone was detected in recrudescence. Co
      administration of artemisone together with chloroquine was more effective than
      monotherapy with either drug, and led to complete cure. Artemiside was even more
      effective than artemisone, but this substance has yet to be submitted to
      preclinical toxicological evaluation. CONCLUSIONS: Altogether, the results
      support the use of artemisone for combined therapy of CM.

PMID- 20691119
TI  - Automated seamless DNA co-transformation cloning with direct expression vectors
      applying positive or negative insert selection.
AB  - BACKGROUND: Molecular DNA cloning is crucial to many experiments and with the
      trend to higher throughput of modern approaches automated techniques are urgently
      required. We have established an automated, fast and flexible low-cost expression
      cloning approach requiring only vector and insert amplification by PCR and co
      transformation of the products. RESULTS: Our vectors apply positive selection for
      the insert or negative selection against empty vector molecules and drive strong
      expression of target proteins in E.coli cells. Variable tags are available both
      in N-terminal or C-terminal position. A newly developed beta-lactamase
      (DeltaW290) selection cassette contains a segment inside the beta-lactamase open
      reading frame encoding a stretch of hydrophilic amino acids that result in a T7
      promoter when back-translated. This position of the promoter permits positive
      selection and attenuated expression of fusion proteins with C-terminal tags. We
      have tested eight vectors by inserting six target sequences of variable length,
      provenience and function. The target proteins were cloned, expressed and detected
      using an automated Tecan Freedom Evo II liquid handling work station. Only two
      colonies had to be picked to score with 85% correct inserts while 80% of those
      were positive in expression tests. CONCLUSIONS: Our results establish co
      transformation and positive/negative selection cloning in conjunction with the
      provided vectors and selection cassettes as an automatable alternative to
      commercialized high-throughput cloning systems like Gateway or ligase-independent
      cloning (LIC) .

PMID- 20691120
TI  - Anopheles larval abundance and diversity in three rice agro-village complexes
      Mwea irrigation scheme, central Kenya.
AB  - BACKGROUND: The diversity and abundance of Anopheles larvae has significant
      influence on the resulting adult mosquito population and hence the dynamics of
      malaria transmission. Studies were conducted to examine larval habitat dynamics
      and ecological factors affecting survivorship of aquatic stages of malaria
      vectors in three agro-ecological settings in Mwea, Kenya. METHODS: Three villages
      were selected based on rice husbandry and water management practices. Aquatic
      habitats in the 3 villages representing planned rice cultivation (Mbui Njeru),
      unplanned rice cultivation (Kiamachiri) and non-irrigated (Murinduko) agro
      ecosystems were sampled every 2 weeks to generate stage-specific estimates of
      mosquito larval densities, relative abundance and diversity. Records of distance
      to the nearest homestead, vegetation coverage, surface debris, turbidity, habitat
      stability, habitat type, rice growth stage, number of rice tillers and percent
      Azolla cover were taken for each habitat. RESULTS: Captures of early, late
      instars and pupae accounted for 78.2%, 10.9% and 10.8% of the total Anopheles
      immatures sampled (n = 29,252), respectively. There were significant differences
      in larval abundance between 3 agro-ecosystems. The village with 'planned' rice
      cultivation had relatively lower Anopheles larval densities compared to the
      villages where 'unplanned' or non-irrigated. Similarly, species composition and
      richness was higher in the two villages with either 'unplanned' or limited rice
      cultivation, an indication of the importance of land use patterns on diversity of
      larval habitat types. Rice fields and associated canals were the most productive
      habitat types while water pools and puddles were important for short periods
      during the rainy season. Multiple logistic regression analysis showed that
      presence of other invertebrates, percentage Azolla cover, distance to nearest
      homestead, depth and water turbidity were the best predictors for Anopheles
      mosquito larval abundance. CONCLUSION: These results suggest that agricultural
      practices have significant influence on mosquito species diversity and abundance
      and that certain habitat characteristics favor production of malaria vectors.
      These factors should be considered when implementing larval control strategies
      which should be targeted based on habitat productivity and water management.

PMID- 20691121
TI  - In vitro effects of imatinib mesylate on radiosensitivity and chemosensitivity of
      breast cancer cells.
AB  - BACKGROUND: Breast cancer treatment is based on a combination of adjuvant
      chemotherapy followed by radiotherapy effecting intracellular signal
      transduction. With the tyrosine kinase inhibitors new targeted drugs are
      available. Imatinib mesylate is a selective inhibitor of bcr-abl, PRGFR alpha,
      beta and c-kit. The purpose of this study was to determine whether Imatinib has
      an influence on the effectiveness of radiotherapy in breast cancer cell lines and
      if a combination of imatinib with standard chemotherapy could lead to increased
      cytoreduction. METHODS: Colony-forming tests of MCF 7 and MDA MB 231 were used to
      study differences in cell proliferation under incubation with imatinib and
      radiation. Changes in expression and phosphorylation of target receptors were
      detected using western blot. Cell proliferation, migration and apoptosis assays
      were performed combining imatinib with doxorubicin. RESULTS: The combination of
      imatinib and radiotherapy showed a significantly stronger inhibition of cell
      proliferation compared to single radiotherapy. Differences in PDGFR expression
      could not be detected, but receptor phosphorylation was significantly inhibited
      when treated with imatinib. Combination of imatinib with standard chemotherapy
      lead to an additive effect on cell growth inhibition compared to single
      treatment. CONCLUSIONS: Imatinib treatment combined with radiotherapy leads in
      breast cancer cell lines to a significant benefit which might be influenced
      through inhibition of PDGFR phosphorylation. Combining imatinib with chemotherapy
      enhances cytoreductive effects. Further in vivo studies are needed to evaluate
      the benefit of Imatinib in combination with radiotherapy and chemotherapy on the
      treatment of breast cancer.

PMID- 20691123
TI  - Continued breathing followed by gasping or apnea in a swine model of ventricular
      fibrillation cardiac arrest.
AB  - BACKGROUND: Continued breathing following ventricular fibrillation has here-to
      fore not been described. METHODS: We analyzed the spontaneous ventilatory
      activity during the first several minutes of ventricular fibrillation (VF) in our
      isoflurane anesthesized swine model of out-of-hospital cardiac arrest. The
      frequency and type of ventilatory activity was monitored by pneumotachometer and
      main stream infrared capnometer and analyzed in 61 swine during the first 3 to 6
      minutes of untreated VF. RESULTS: During the first minute of VF, the air flow
      pattern in all 61 swine was similar to those recorded during regular spontaneous
      breathing during anesthesia and was clearly different from the patterns of
      gasping. The average rate of continued breathing during the first minute of
      untreated VF was 10 breaths per minute. During the second minute of untreated VF,
      spontaneous breathing activity either stopped or became typical of gasping.
      During minutes 2 to 5 of untreated VF, most animals exhibited very slow
      spontaneous ventilatory activity with a pattern typical of gasping; and the
      pattern of gasping was crescendo-decrescendo, as has been previously reported. In
      the absence of therapy, all ventilatory activity stopped 6 minutes after VF
      cardiac arrest. CONCLUSION: In our swine model of VF cardiac arrest, we
      documented that normal breathing continued for the first minute following cardiac
      arrest.

PMID- 20691122
TI  - Automated quantitative gait analysis in animal models of movement disorders.
AB  - BACKGROUND: Accurate and reproducible behavioral tests in animal models are of
      major importance in the development and evaluation of new therapies for central
      nervous system disease. In this study we investigated for the first time gait
      parameters of rat models for Parkinson's disease (PD), Huntington's disease (HD)
      and stroke using the Catwalk method, a novel automated gait analysis test. Static
      and dynamic gait parameters were measured in all animal models, and these data
      were compared to readouts of established behavioral tests, such as the cylinder
      test in the PD and stroke rats and the rotarod tests for the HD group. RESULTS:
      Hemiparkinsonian rats were generated by unilateral injection of the neurotoxin 6
      hydroxydopamine in the striatum or in the medial forebrain bundle. For
      Huntington's disease, a transgenic rat model expressing a truncated huntingtin
      fragment with multiple CAG repeats was used. Thirdly, a stroke model was
      generated by a photothrombotic induced infarct in the right sensorimotor cortex.
      We found that multiple gait parameters were significantly altered in all three
      disease models compared to their respective controls. Behavioural deficits could
      be efficiently measured using the cylinder test in the PD and stroke animals, and
      in the case of the PD model, the deficits in gait essentially confirmed results
      obtained by the cylinder test. However, in the HD model and the stroke model the
      Catwalk analysis proved more sensitive than the rotarod test and also added new
      and more detailed information on specific gait parameters. CONCLUSION: The
      automated quantitative gait analysis test may be a useful tool to study both
      motor impairment and recovery associated with various neurological motor
      disorders.

PMID- 20691124
TI  - Nutritional sensitivity of periparturient resistance to nematode parasites in two
      breeds of sheep with different nutrient demands.
AB  - The periparturient relaxation of immunity (PPRI) to parasites in mammals is
      sensitive to both metabolisable protein (MP) supply and animal genotype
      (different reproductive outputs). We tested the hypothesis that the sensitivity
      of PPRI to MP scarcity would not differ between different levels of reproductive
      output when nutrient intake is adjusted for associated differences in MP demand;
      this hypothesis assumes that PPRI has a nutritional basis only. Scottish
      Blackface (BF) and the more productive Mule (MU) ewes were infected with the
      abomasal parasite Teladorsagia circumcincta, and from day -21 to day 32 (day 0 is
      parturition), they were fed restrictedly at either 0.8 (low protein (LP)) or 1.3
      (high protein (HP)) times their breed-specific estimated MP requirement (n 18 for
      each breed-feeding treatment combination). During late pregnancy, LP feeding
      reduced ewe body weight gain in both breeds, tended to increase faecal egg count
      (FEC), but it did not affect plasma pepsinogen. During lactation, LP feeding
      reduced litter growth rate and ewe plasma urea and plasma albumin concentrations
      compared with HP feeding in both breeds. However, breed and feeding treatment
      interacted for ewe FEC, worm egg excretion and plasma pepsinogen, which were
      higher for the LP-MU ewes compared with the HP-MU and BF ewes. The lower degree
      of PPRI of the BF ewes during lactation compared with the MU ewes at a similar
      degree of MP scarcity suggests that the effect of reproductive output on
      nutritional sensitivity of PPRI cannot be explained by associated differences in
      nutrient demand only.

PMID- 20691125
TI  - Dietary histidine supplementation prevents cataract development in adult Atlantic
      salmon, Salmo salar L., in seawater.
AB  - The aim of the present study was to investigate the cataract preventive effect of
      dietary histidine regimes in adult Atlantic salmon (Salmo salar L.) in seawater,
      both through manipulating the dietary histidine level and feeding period. Mean
      body weight of individually tagged Atlantic salmon at the start of the experiment
      was 1662 (sd 333) g. Low prevalence of mild cataracts were recorded in the
      beginning of June. Three fishmeal and fish oil-based extruded diets (crude
      protein: 375 g/kg and fat: 342 g/kg), differing only in histidine content (low
      (L): 9.3, medium (M): 12.8 and high (H): 17.2 g histidine/kg diets), were fed to
      duplicate net pens in seawater. The experimental period was divided into three
      seasons (June-July; July-September; September-October), each starting and ending
      with individual cataract examination, assessment of somatic data, and sampling of
      lens and muscle tissues for analysis of histidine and histidine derivatives. In
      July and September, a part of the population fed L- and H-histidine feeds were
      transferred (crossed over) to respective series of replicate net pens fed L-, M-
      and H-histidine diets (i.e. eleven experimental feeding groups at trial
      conclusion). The fish doubled their body weight from June to October, with no
      systematic effects on weight gain of dietary histidine feeding regimes.
      Development of severe cataracts was observed between July and September. The
      cataract severity was directly related to the dietary histidine level fed during
      the first and second periods. Feeding histidine-supplemented diets (M or H) in
      the first period from June to July mitigated later cataract outbreaks. The status
      of selected free imidazoles in muscle and lens tissues reflected the dietary
      histidine feeding regimes, relative to both feed concentration and feeding
      duration. The study shows the risk for cataract development for adult Atlantic
      salmon, 1 year after the transfer of salmon smolts from freshwater to seawater,
      which to a major extent can be prevented by histidine supplementation just before
      and during the early phase of cataract development.

PMID- 20691126
TI  - Effects of a dietary intervention promoting the adoption of a Mediterranean food
      pattern on fast-food consumption among healthy French-Canadian women.
AB  - It is expected that a dietary intervention based on the traditional Mediterranean
      food pattern should be associated with a reduction in fast-food consumption but
      this has never been tested before. We assessed the impact of a 12-week dietary
      intervention, promoting the adoption of a Mediterranean food pattern, on fast
      food consumption among seventy-one healthy women aged between 30 and 65 years.
      The dietary intervention consisted of two group sessions and seven individual
      sessions with a dietitian. To determine the Mediterranean dietary score
      (MedScore) and fast-food consumption, an FFQ was administered. During the 12-week
      intervention, the MedScore significantly increased (from 21.1 (SD 3.6) units at
      baseline to 28.6 (SD 4.4) units at week 12, P < 0.0001), while the fast-food
      consumption significantly decreased (from 51.7 (SD 46.4) g/d at baseline to 20.5
      (SD 18.2) g/d at week 12, P < 0.0001). Moreover, women who had a higher
      consumption of fast food at baseline decreased their fast-food consumption to the
      most (r - 0.50, P < 0.0001). When four subgroups were formed on the basis of
      median values of Medscore and fast-food consumption changes, it was found that
      only the subgroup of women which increased the most their MedScore and decreased
      the most their fast-food consumption experienced a significant decrease in BMI (P
      < 0.01). In conclusion, a dietary intervention promoting the Mediterranean food
      pattern led to a decrease in fast-food consumption among healthy women even if it
      was not a specific target of the intervention. Dietary strategies for increasing
      intake of healthy foods may be a useful approach for decreasing intake of less
      healthy foods.

PMID- 20691127
TI  - Whey peptides improve wound healing following caesarean section in rats.
AB  - We sought to determine whether postcaesarean treatment with whey peptides (WP)
      affects the healing of skin and uterine incision in rats during puerperium. Forty
      eight rats were randomly divided into two groups. After a caesarean section,
      twenty-four rats were intragastrically administered WP, while others were
      administered a control vehicle. On days 7, 14 and 21 after delivery, the serum
      total protein/albumin concentration, skin tensile strength, uterine bursting
      pressure, skin/uterine hydroxyproline (Hyp) concentration and histological
      characteristics of the scar were measured in eight rats in each group. In the WP
      group, the albumin concentration, skin tensile strength, uterine bursting
      pressure and Hyp concentration in the skin increased significantly on days 21, 7,
      14 and 21, respectively. Low neutrophil count and smaller scar width in the skin
      incision were found in the WP group on day 7. Postcaesarean treatment with WP
      promoted significant wound healing in the skin incision, and had a significant
      wound healing potential in the uterus.

PMID- 20691128
TI  - Plasma appearance and correlation between coffee and green tea metabolites in
      human subjects.
AB  - Coffee and green tea are two of the most widely consumed hot beverages in the
      world. Their respective bioavailability has been studied separately, but
      absorption of their respective bioactive phenolics has not been compared. In a
      randomised cross-over design, nine healthy subjects drank instant coffee and
      green tea. Blood samples were collected over 12 h and at 24 h to assess return to
      baseline. After green tea consumption, (-)-epigallocatechin (EGC) was the major
      catechin, appearing rapidly in the plasma; (-)-EGC gallate (EGCg) and (-)
      epicatechin (EC) were also present, but (-)-EC gallate and C were not detected.
      Dihydroferulic acid and dihydrocaffeic acid were the major metabolites that
      appeared after coffee consumption with a long time needed to reach maximum plasma
      concentration, suggesting metabolism and absorption in the colon. Other phenolic
      acid equivalents (caffeic acid (CA), ferulic acid (FA) and isoferulic acid (iFA))
      were detected earlier, and they peaked at lower concentrations. Summations of the
      plasma area under the curves (AUC) for the measured metabolites showed 1.7-fold
      more coffee-derived phenolic acids than green tea-derived catechins (P = 0.0014).
      Furthermore, we found a significant correlation between coffee metabolites based
      on AUC. Inter-individual differences were observed, but individuals with a high
      level of CA also showed a correspondingly high level of FA. However, no such
      correlation was observed between the tea catechins and coffee phenolic acids.
      Correlation between AUC and maximum plasma concentration was also significant for
      CA, FA and iFA and for EGCg. This implies that the mechanisms of absorption for
      these two classes of compounds are different, and that a high absorber of
      phenolic acids is not necessarily a high absorber of catechins.

PMID- 20691129
TI  - Time-dependent changes in the expression of lymphocyte and monocyte cell adhesion
      molecules after meals of different composition.
AB  - The objective of the present study was to compare the acute effect of meals of
      different composition on the expression of adhesion molecules that play a key
      role in leucocyte trafficking. A total of twenty apparently healthy subjects
      randomly consumed three isoenergetic meals 1 week apart: enriched in
      carbohydrates (CHO), enriched in monounsaturated fat and enriched in saturated
      fat. Blood samples were obtained before the meals and at 2, 4, 6, 8 and 10 h
      after meal ingestion. Samples were analysed for LDL resistance to Cu-mediated
      oxidation and for the surface expression on peripheral blood mononuclear cells
      (PBMC) of CD62L, CD162, CD11a, CD11b, CD49d and CD54 by flow cytometry. The
      present results showed that there were no changes in LDL susceptibility to
      oxidation within and among the meals. After the CHO-enriched meal, there was a
      time-dependent increased expression of CD162, CD49d, CD11a and CD54 on PBMC that
      returned to basal values after 8-10 h. These changes were significantly greater
      than the ones observed after the consumption of the monounsaturated fat- and the
      saturated fat-enriched meals and were more evident in lymphocytes than in
      monocytes. In conclusion, acute ingestion of a CHO-enriched meal induces higher
      increases of lymphocyte activation markers than fat-enriched meals. These results
      suggest that long-term consumption of CHO-enriched diets may be associated with a
      sustained pro-inflammatory state.

PMID- 20691130
TI  - Potent anti-obesity effect of enteric-coated lactoferrin: decrease in visceral
      fat accumulation in Japanese men and women with abdominal obesity after 8-week
      administration of enteric-coated lactoferrin tablets.
AB  - Lactoferrin (LF), a multifunctional glycoprotein in mammalian milk, is reported
      to exert a modulatory effect on lipid metabolism. The aim of the present study
      was to elucidate whether enteric-coated LF (eLF) might improve visceral fat-type
      obesity, an underlying cause of the metabolic syndrome. Using a double-blind,
      placebo-controlled design, Japanese men and women (n 26; aged 22-60 years) with
      abdominal obesity (BMI>25 kg/m2, and visceral fat area (VFA)>100 cm2) consumed
      eLF (300 mg/d as bovine LF) or placebo tablets for 8 weeks. Measurement of the
      total fat area, VFA and subcutaneous fat area from computed tomography images
      revealed a significant reduction in VFA ( - 14.6 cm2) in the eLF group, as
      compared with the placebo controls ( - 1.8 cm2; P = 0.009 by ANCOVA). Decreases
      in body weight, BMI and hip circumference in the eLF group ( - 1.5 kg, - 0.6
      kg/m2, - 2.6 cm) were also found to be significantly greater than with the
      placebo (+1.0 kg, +0.3 kg/m2, - 0.2 cm; P = 0.032, 0.013, 0.041, respectively).
      There was also a tendency for a reduction in waist circumference in the eLF group
      ( - 4.4 cm) as compared with the placebo group ( - 0.9 cm; P = 0.073). No adverse
      effects of the eLF treatment were found with regard to blood lipid or biochemical
      parameters. From these results, eLF appears to be a promising agent for the
      control of visceral fat accumulation.

PMID- 20691131
TI  - Tolerance and safety of the potentially probiotic strain Lactobacillus rhamnosus
      PRSF-L477: a randomised, double-blind placebo-controlled trial in healthy
      volunteers.
AB  - In Europe, the species Lactobacillus rhamnosus is currently on the Qualified
      Presumption of Safety list used by the European Food Safety Authority (EFSA) for
      internal safety assessment, but according to the EFSA the species should remain a
      topic of surveillance. In the present study, the safety and tolerance of the
      potentially probiotic strain L. rhamnosus PRSF-L477 was investigated in a placebo
      controlled double-blind volunteer trial following FAO/WHO guidelines. A total of
      thirty-four subjects received daily doses of 1 * 1011 colony-forming units (cfu)
      of L. rhamnosus PRSF-L477 (n 17) or placebo (n 17) for a period of 3 weeks,
      followed by a wash-out period of another 3 weeks. A questionnaire on
      gastrointestinal tolerance and a diary was kept daily to record compliance
      throughout these 6 weeks. Faecal and blood samples were collected for
      microbiological and haematological analysis. The recorded gastrointestinal
      symptoms, defecation frequency and stool consistency were not influenced
      indicating that L. rhamnosus PRSF-L477 was well tolerated. The species L.
      rhamnosus was detected in the faeces of sixteen out of seventeen subjects of the
      probiotic group during the intervention period. Using pulsed-field gel
      electrophoresis, re-isolates of L. rhamnosus PRSF-L477 were confirmed in nine of
      these subjects. Antibiotic susceptibility profiles of these re-isolates were
      unchanged compared with PRSF-L477. No clinically relevant changes in blood
      parameters such as liver and kidney function and no serious adverse events
      appeared during and after administration. Therefore, we conclude that L.
      rhamnosus PRSF-L477 can safely be administrated to healthy subjects at a daily
      dose of 1 * 1011 cfu.

PMID- 20691132
TI  - Monosodium glutamate is not associated with obesity or a greater prevalence of
      weight gain over 5 years: findings from the Jiangsu Nutrition Study of Chinese
      adults--comments by Samuels.

PMID- 20691134
TI  - Genetic variation of the FADS1 FADS2 gene cluster and n-6 PUFA composition in
      erythrocyte membranes in the European Prospective Investigation into Cancer and
      Nutrition-Potsdam study.
AB  - Delta-5 (D5D) and delta-6 (D6D) desaturases are key enzymes in PUFA metabolism.
      Several factors (e.g. hyperglycaemia, hypertension, blood lipids, statins and
      fatty acids in diet and biological tissues) may influence desaturase activity.
      The goals were to evaluate the associations between variation in genes encoding
      these desaturases (FADS1 and FADS2) and blood concentrations of n-6 PUFA and
      estimated D5D and D6D activities (evaluated as product/precursor ratio), and to
      investigate whether other factors influencing the activity of desaturases modify
      these associations. A random sample of 2066 participants from the European
      Prospective Investigation into Cancer and Nutrition-Potsdam study (n 27 548) was
      utilised in the analyses. Crude and adjusted associations between rs174546
      genotypes (reflecting genetic variation in the FADS1 FADS2 gene cluster), n-6
      PUFA in erythrocytes and estimated desaturase activities were evaluated using
      multiple linear regression. Potential effect modification was determined by
      performing stratified analyses and evaluating interaction terms. We found
      rs174546 genotypes to be related to linoleic (r2 0.060), gamma-linolenic (r2
      0.041), eicosadienoic (r2 0.034), arachidonic (r2 0.026), docosatetraenoic acids
      (r2 0.028), estimated D6D activity (r2 0.052) and particularly strongly to dihomo
      gamma-linolenic acid (DGLA, r2 0.182) and D5D activity (r2 0.231). We did not
      observe effect modifications with regard to the estimated D5D activity, DGLA and
      arachidonic acid (AA) for most of the factors evaluated; however, the genetic
      effect on D5D activity and DGLA may be modified by the dietary n-6:n-3-ratio (P
      values for interaction: 0.008 and 0.002), and the genetic effect on DGLA and AA
      may be modified by lipid-lowering medication (P-values for interaction: 0.0004
      and 0.006). In conclusion, genetic variation in the FADS1 FADS2 gene cluster
      affects n-6 PUFA profiles in erythrocytes reflecting altered D5D activity.

PMID- 20691135
TI  - Dietary fish oil reduces skeletal muscle oxygen consumption, provides fatigue
      resistance and improves contractile recovery in the rat in vivo hindlimb.
AB  - Dietary fish oil modulates skeletal muscle membrane fatty acid composition.
      Similar changes in heart membrane composition modulate myocardial oxygen
      consumption and enhance mechanical performance. The rat in vivo autologous
      perfused hindlimb was used to investigate the influence of membrane composition
      on skeletal muscle function. Male Wistar rats were fed either saturated fat (SF),
      n-6 PUFA (linoleic acid rich) or n-3 PUFA (fish oil) diets for 8 weeks. Hindlimb
      skeletal muscle perfused using the animal's own blood was stimulated via the
      sciatic nerve (1 Hz, 6-12 V, 0.05 ms) to contract in repeated 10 min bouts. The n
      3 PUFA diet markedly increased 22 : 6n-3 DHA, total n-3 PUFA and decreased the n
      6:n-3 PUFA ratio (P < 0.05) in red and white skeletal muscle membranes. There was
      no difference in initial twitch tension but the n-3 PUFA group maintained greater
      twitch tension within all contraction bouts and recovered better during rest to
      produce greater twitch tension throughout the final contraction bout (P < 0.05).
      Hindlimb oxygen consumption during contraction was significantly lower in the n-3
      PUFA group compared with the SF group, producing a significantly higher O2
      efficiency index compared with both SF and n-6 PUFA groups (P < 0.05). Resting
      oxygen consumption was increased in recovery in the SF group (P < 0.05) but did
      not change in the n-3 PUFA group. Membrane incorporation of n-3 PUFA DHA
      following fish oil feeding was associated with increased efficiency of muscle O2
      consumption and promoted resistance to muscle fatigue.

PMID- 20691136
TI  - Chronic administration of Eucommia leaf stimulates metabolic function of rats
      across several organs.
AB  - Eucommia bark (Eucommia ulmoides Oliver) has been used as an herbal medicine, and
      more recently, the plant's leaves have been widely used to prepare tea which may
      have anti-obesity properties. We used a metabolic syndrome-like rat model,
      produced by feeding a 35% high-fat diet (HFD), to examine potential anti-obesity
      and anti-metabolic syndrome effects and mechanisms of chronic administration of
      Eucommia leaf as an extract or green leaf powder. Eighty rats were studied for 3
      months in ten groups. Both forms of Eucommia leaves minimised increases in body
      weight and visceral fat in a dose-dependent fashion. Increases in plasma levels
      of TAG and NEFA, and insulin resistance secondary to HFD were lessened by both
      forms of Eucommia leaf. Concomitantly, an increase in plasma adiponectin levels
      and suppression of plasma resistin and TNF-alpha levels were confirmed. Real-time
      PCR studies showed that both forms of Eucommia leaf enhanced metabolic function
      across several organs, including diminishing ATP production (white adipose
      tissue), accelerating beta-oxidation (liver) and increasing the use of ketone
      bodies/glucose (skeletal muscle), all of which may exert anti-obesity effects
      under HFD conditions. These findings suggest that chronic administration of
      either form of Eucommia leaves stimulates the metabolic function in rats across
      several organs. The anti-obesity and anti-metabolic syndrome activity in this rat
      model may be maintained through secretion and regulation of adipocytokines that
      depend on the accumulation of visceral fat to improve insulin resistance or
      hyperlipaemia.

PMID- 20691137
TI  - Dietary calcium decreases but short-chain fructo-oligosaccharides increase
      colonic permeability in rats.
AB  - An increased intestinal permeability is associated with several diseases.
      Nutrition can influence gut permeability. Previously, we showed that dietary Ca
      decreases whereas dietary short-chain fructo-oligosaccharides (scFOS) increase
      intestinal permeability in rats. However, it is unknown how and where in the
      gastrointestinal tract Ca and scFOS exert their effects. Rats were fed a Western
      low-Ca control diet, or a similar diet supplemented with either Ca or scFOS.
      Lactulose plus mannitol and Cr-EDTA were added to the diets to quantify small and
      total gastrointestinal permeability, respectively. Additionally, colonic tissue
      was mounted in Ussing chambers and exposed to faecal water of these rats. Dietary
      Ca immediately decreased urinary Cr-EDTA excretion by 24 % in Ca-fed rats
      compared with control rats. Dietary scFOS increased total Cr-EDTA permeability
      gradually with time, likely reflecting relatively slow gut microbiota
      adaptations, which finally resulted in a 30 % increase. The lactulose:mannitol
      ratio was 15 % higher for Ca-fed rats and 16 % lower for scFOS-fed rats compared
      with control rats. However, no dietary effect was present on individual urinary
      lactulose and mannitol excretion. The faecal waters did not influence colonic
      permeability in Ussing chambers. In conclusion, despite effects on the
      lactulose:mannitol ratio, individual lactulose values did not alter, indicating
      that diet did not influence small-intestinal permeability. Therefore, both
      nutrients affect permeability only in the colon: Ca decreases, while scFOS
      increase colonic permeability. As faecal water did not influence permeability in
      Ussing chambers, probably modulation of mucins and/or microbiota is important for
      the in vivo effects of dietary Ca and scFOS.

PMID- 20691139
TI  - Resolving disagreement during end of life care in the critical care unit: the
      case for communication not arbitration.

PMID- 20691140
TI  - Translational applications of microRNA genes in medulloblastomas.
AB  - PURPOSE: To provide a critical assessment of the clinical translational
      applications of microRNA (miRNA) genes in medulloblastomas. METHODS: Data were
      obtained from MEDLINE using Boolean-formatted keyword queries. Top articles were
      selected for critical analyses - depending on the novelty of findings,
      qualitative assessment of the citation index and relevance to the diagnosis,
      prognosis and therapeutic targeting of medulloblastomas. RESULTS: MiRNAs, non
      protein-coding RNA molecules, negatively regulate gene expression in a sequence
      specific manner during biological processes. In the past few years, miRNA genes
      have emerged as key regulators of not only molecular events involved in normal
      brain development and function but also in the molecular pathogenesis of
      medulloblastomas. In this manner, microRNA genes are identified with functional
      roles as oncogenes and tumor suppressor genes. At least four miRNAs have proven
      useful in improving the molecular classification of medulloblastomas, and eight
      others have shown potential in predicting patients' overall prognosis. Moreover,
      more than 10 miRNA genes can be potentially utilized in therapies against
      medulloblastomas, using nine recent methods of targetting miRNAs. CONCLUSION: The
      quest to identify miRNA genes that are of biological significance in
      medulloblastomas is on an ongoing venture. Most importantly, these miRNAs have
      been shown to be of clinical importance for improving the accuracy of diagnosis
      and prognosis and even developing therapies that can significantly improve
      patients' overall survival from this deadly disease.

PMID- 20691138
TI  - Rate theories for biologists.
AB  - Some of the rate theories that are most useful for modeling biological processes
      are reviewed. By delving into some of the details and subtleties in the
      development of the theories, the review will hopefully help the reader gain a
      more than superficial perspective. Examples are presented to illustrate how rate
      theories can be used to generate insight at the microscopic level into
      biomolecular behaviors. An attempt is made to clear up a number of misconceptions
      in the literature regarding popular rate theories, including the appearance of
      Planck's constant in the transition-state theory and the Smoluchowski result as
      an upper limit for protein-protein and protein-DNA association rate constants.
      Future work in combining the implementation of rate theories through computer
      simulations with experimental probes of rate processes, and in modeling effects
      of intracellular environments so that theories can be used for generating rate
      constants for systems biology studies is particularly exciting.

PMID- 20691141
TI  - Clinical hallmarks and genetic polymorphisms in the CFTR gene contribute to the
      disclosure of the A1006E mutation.
AB  - Since the identification of the Cystic Fibrosis transmembrane conductance
      regulator (CFTR) gene in 1989, many genetic mutations have been found in cystic
      fibrosis (CF) patients. Dysfunctions of the CFTR gene are responsible for the
      highly variable clinical presentation ranging from severe CF, disseminated
      bronchiectasis, idiopathic chronic pancreatitis and congenital bilateral absence
      of vas deferens (CBAVD). Linkage disequilibrium studies have shown that some
      mutations are stringently coupled with polymorphisms in a genetic complex called
      haplotype. From a familial study of a patient with CBAVD, carrier of the A1006E
      mutation, we have observed its strict association with the polymorphism 5T-TG11.
      In order to speed up the genetic diagnosis and to correlate the clinical setting
      to this genetic feature, we have directly investigated the exon 17a, where the
      A1006E mutation is located, of five cystic fibrosis patients belonging to two
      unrelated families. All patients had the 5T-TG11 tract, F508del and one unknown
      mutation. One more family with two affected individuals carrying the Q220X/A1006E
      mutations was investigated for the poly-T polymorphism. All the members were
      found to have the A1006E mutation and the 5T-TG11 in the same DNA strand,
      demonstrating that this strategy is a reliable and inexpensive method for
      genotyping the CFTR gene. A detailed description of the clinical presentation and
      follow-up are provided in order to highlight common phenotypic features useful to
      improve the management of cystic fibrosis patients.

PMID- 20691142
TI  - A framework for resolving disagreement during end of life care in the critical
      care unit.
AB  - BACKGROUND: End-of-life decisions regarding the administration, withdrawal or
      withholding of life-sustaining therapy in the critical care setting can be
      challenging. Disagreements between health care providers and family members
      occur, especially when families believe strongly in preserving life, and
      physicians are resistant to providing medically "futile" care. Such disagreements
      can cause tension and moral distress among families and clinicians. PURPOSE: To
      outline the roles and responsibilities of physicians, substitute decision makers,
      and the judicial system when decisions must be made on behalf of incapable
      persons, and to provide a framework for conflict resolution during end-of-life
      decision-making for physicians practicing in Canada. SOURCE: We used a case-based
      example to illustrate our objectives. We employed a comprehensive approach to
      understanding end-of-life decision making that included: 1) a search for relevant
      literature; 2) a review of provincial college policies; 3) a review of provincial
      legislation on consent; 4) a consultation with two bioethicists and 5) a
      consultation with two legal experts in health law. PRINCIPAL FINDINGS: In Canada,
      laws about substitute decision-making for health care are primarily provincial or
      territorial. Thus, laws and policies from professional regulatory bodies on end
      of-life care vary across the country. We tabulated the provincial college
      policies on end-of-life care and the provincial legislation on consent and
      advance directives, and constructed a 10-step approach to conflict resolution.
      CONCLUSION: Knowledge of underlying ethical principles, understanding of
      professional duties, and adoption of a process for mediation and conflict
      resolution are essential to ensuring that physicians and institutions act
      responsibly in maintaining a patients' best interests in the context of family
      centred care.

PMID- 20691143
TI  - Prevention of postoperative peritoneal adhesions by O-carboxymethyl chitosan in a
      rat cecal abrasion model.
AB  - PURPOSE: Post-surgical adhesion formation can result in significant morbidity and
      mortality. N,O-carboxymethyl chitosan (N,O-CMC) has been previously shown to be
      effective in the prevention of postsurgical adhesion formation. In this study, we
      evaluated the ability of O-carboxymethyl chitosan (O-CMC), another chitosan
      derivative generated by carboxymethylation of chitosan's oxygen centers, to
      reduce postsurgical adhesion development. METHODS: Twenty male Sprague-Dawley
      rats (250 +/- 20 g) were divided into two equal groups: O-CMC group and saline
      (control) group. All rats underwent a midline laparotomy and the cecum was
      abraded to cause petechial hemorrhages. Following peritoneal injections of either
      saline or O-CMC, the incisions were closed. Seven days after surgery, the animals
      were killed and adhesion formation was scored. Tissue samples from the adhesions
      were examined histochemically. RESULTS: Adhesion formation was significantly
      decreased in the O-CMC group (P < .001) in comparison with the control group.
      Furthermore, significantly less collagen (P < .001) and fewer inflammatory cells
      and fibroblasts were detected in the O-CMC-treated animals. Additionally, a
      significantly (P < .05) lower level of TGF-beta1 expression was found in the O
      CMC group. CONCLUSION: O-CMC appears to be effective in the prevention of
      postoperative peritoneal adhesion formation, which may be attributed to decreased
      accumulation of inflammatory cells and fibroblasts and reduced collagen
      synthesis.

PMID- 20691144
TI  - A questionnaire assessment of physical function in hyperlipidemic patients.
AB  - BACKGROUND: A spectrum of myopathic manifestations has been recognized as
      associated with lipid lowering drug therapy (LLT), but their effect on quality of
      life and physical functioning is uncertain. We conducted a prospective cohort
      study in which physical functioning was the dependent variable, in patients with
      and without exposure to LLT. METHODS: Consecutive patients attending a risk
      reduction clinic were invited to participate in a questionnaire study which
      included demographic data, muscular symptoms, the SF-36 Physical Function Score
      (PF), and the modified Health Assessment Questionnaire (mHAQ). Laboratory and co
      morbidity data was recorded. RESULTS: Of 117 consecutive patients invited to
      participate, 112 consented. Of these, 81 were receiving statins and/or fibrates
      as LLT and 31 were participating in a non-pharmacologic therapeutic program (NPT)
      of diet and exercise therapy. The mean age for the total population was 56.7
      years (20-78): the LLT group 58.6 and NPT group 51.9 years. Women comprised 53%
      of the LLT group and 58% of the NPT. No significant differences in baseline lipid
      profiles, CK level, BMI, waist measurement, gender, cigarette smoking, alcohol
      consumption, non-steroidal anti-inflammatory drugs or acetaminophen use,
      frequency of myalgias, SF-36 PF or mHAQ scores were observed between groups. On
      comparison of gender groups, we observed that men receiving LLT had significantly
      better SF- 36 PF (p = 0.037) than men on NPT. There were no differences in SF-36
      PF or mHAQ scores between groups for females. CONCLUSION: We found no adverse
      effects of LLT on physical functioning or quality of life. Indeed, men treated
      with LLT had significantly better SF-36 PF scores than men treated non
      pharmacologically.

PMID- 20691145
TI  - Proton transport coupled ATP synthesis by the purified yeast H+ -ATP synthase in
      proteoliposomes.
AB  - The H(+)/ATP synthase from yeast mitochondria, MF0F1, was purified and
      reconstituted into liposomes prepared from phosphatidylcholine and phosphatidic
      acid. Analysis by mass spectrometry revealed the presence of all subunits of the
      yeast enzyme with the exception of the K-subunit. The MF0F1 liposomes were
      energized by acid-base transitions (DeltapH) and a K(+)/valinomycin diffusion
      potential (Deltaphi). ATP synthesis was completely abolished by the addition of
      uncouplers as well as by the inhibitor oligomycin. The rate of ATP synthesis was
      optimized as a function of various parameters and reached a maximum value
      (turnover number) of 120s-1 at a transmembrane pH difference of 3.2 units (at
      pH(in)=4.8 and pH(out)=8.0) and a Deltaphi of 133mV (Nernst potential).
      Functional studies showed that the monomeric MF0F1, was fully active in ATP
      synthesis. The turnover increased in a sigmoidal way with increasing internal and
      decreasing external proton concentration. The dependence of the turnover on the
      phosphate concentration and the dependence of K(M) on pH(out) indicated that the
      substrate for ATP synthesis is the monoanionic phosphate species H2PO-4.

PMID- 20691146
TI  - Characterizing a monotopic membrane enzyme. Biochemical, enzymatic and
      crystallization studies on Aquifex aeolicus sulfide:quinone oxidoreductase.
AB  - Monotopic membrane proteins are membrane proteins that interact with only one
      leaflet of the lipid bilayer and do not possess transmembrane spanning segments.
      They are endowed with important physiological functions but until now only few of
      them have been studied. Here we present a detailed biochemical, enzymatic and
      crystallographic characterization of the monotopic membrane protein
      sulfide:quinone oxidoreductase. Sulfide:quinone oxidoreductase is a ubiquitous
      enzyme involved in sulfide detoxification, in sulfide-dependent respiration and
      photosynthesis, and in heavy metal tolerance. It may also play a crucial role in
      mammals, including humans, because sulfide acts as a neurotransmitter in these
      organisms. We isolated and purified sulfide:quinone oxidoreductase from the
      native membranes of the hyperthermophilic bacterium Aquifex aeolicus. We studied
      the pure and solubilized enzyme by denaturing and non-denaturing polyacrylamide
      electrophoresis, size-exclusion chromatography, cross-linking, analytical
      ultracentrifugation, visible and ultraviolet spectroscopy, mass spectrometry and
      electron microscopy. Additionally, we report the characterization of its
      enzymatic activity before and after crystallization. Finally, we discuss the
      crystallization of sulfide:quinone oxidoreductase in respect to its membrane
      topology and we propose a classification of monotopic membrane protein crystal
      lattices. Our data support and complement an earlier description of the three
      dimensional structure of A. aeolicus sulfide:quinone oxidoreductase (M. Marcia,
      U. Ermler, G. Peng, H. Michel, Proc Natl Acad Sci USA, 106 (2009) 9625-9630) and
      may serve as a reference for further studies on monotopic membrane proteins.

PMID- 20691147
TI  - Ice-induced partial unfolding and aggregation of an integral membrane protein.
AB  - Although the deleterious effects of ice on water-soluble proteins are well
      established, little is known about the freeze stability of membrane proteins.
      Here we explore this issue through a combined kinetic and spectroscopic approach
      using micellar-purified plasma membrane calcium pump as a model. The ATPase
      activity of this protein significantly diminished after freezing using a slow
      cooling procedure, with the decrease in the activity being an exponential
      function of the storage time at 253K, with t(1/2)=3.9+/-0.6h. On the contrary, no
      significant changes on enzyme activity were detected when a fast cooling
      procedure was performed. Regardless of the cooling rate, successive freeze-thaw
      cycles produced an exponential decrease in the Ca(2+)-ATPase activity, with the
      number of cycles at which the activity was reduced to half being 9.2+/-0.3 (fast
      cooling) and 3.7+/-0.2 (slow cooling). PAGE analysis showed that neither
      degradation nor formation of SDS-stable aggregates of the protein takes place
      during protein inactivation. Instead, the inactivation process was found to be
      associated with the irreversible partial unfolding of the polypeptide chain, as
      assessed by Trp fluorescence, far UV circular dichroism, and 1-anilino-naphtalene
      8-sulfonate binding. This inactive protein undergoes, in a later stage, a further
      irreversible transformation leading to large aggregates.

PMID- 20691148
TI  - Mitoxantrone is expelled by the ABCG2 multidrug transporter directly from the
      plasma membrane.
AB  - ABC multidrug transporter proteins expel a wide variety of structurally
      unrelated, mostly hydrophobic compounds from cells. The special role of these
      transporters both at the physiological barriers and in cancer cells is based on
      their extremely broad substrate recognition. Since hydrophobic compounds are
      known to partition into the lipid bilayer and accumulate in membranes, the
      "classical pump" model for the mechanism of multidrug transporter proteins has
      been challenged, and alternative models suggesting substrate recognition within
      the lipid bilayer have been proposed. Although much effort has been made to
      validate this concept, unambiguous evidence for direct drug extrusion from the
      plasma membrane has not been provided yet. Here we show a detailed on-line
      microscopic analysis of cellular extrusion of fluorescent anti-cancer drugs,
      mitoxantrone and pheophorbide A, by a key human multidrug transporter, ABCG2.
      Using the fully active GFP-tagged ABCG2 and exploiting the special character of
      mitoxantrone that gains fluorescence in the lipid environment, we were able to
      determine transporter-modulated drug concentrations separately in the plasma
      membrane and the intracellular compartments. Different kinetic models describing
      the various transport mechanisms were generated and the experimental data were
      analyzed using these models. On the basis of the kinetic analysis, drug extrusion
      from the cytoplasm can be excluded, thus, our results indicate that ABCG2
      extrudes mitoxantrone directly from the plasma membrane.

PMID- 20691149
TI  - The multidrug resistance half-transporter ABCG2 is purified as a tetramer upon
      selective extraction from membranes.
AB  - ABCG2 is a human membrane ATP-binding cassette half-transporter that hydrolyzes
      ATP to efflux a large number of chemotherapeutic agents. Several oligomeric
      states of ABCG2 from homodimers to dodecamers have been reported depending on the
      overexpression systems and/or the protocols used for purification. Here, we
      compared the oligomeric state of His(6)-ABCG2 expressed in Sf9 insect cells and
      in human Flp-In-293/ABCG2 cells after solubilization in mild detergents. His(6)
      ABCG2 was purified through a new approach involving its specific recognition onto
      a functionalized lipid layer containing a Ni-NTA lipid. This approach allowed the
      purification of His-ABCG2 in presence of all solubilized membrane components that
      might be involved in the stabilisation of native oligomers and without requiring
      any additional washing or concentration passages. ABCG2 purified onto the NiNTA
      lipid surfaces were directly analyzed by electron microscopy and by biochemical
      assays. Altogether, our data are consistent with a tetrameric organization of
      ABCG2 when expressed in either heterologous Sf9 insect cells or in human
      homologous cells.

PMID- 20691150
TI  - Amino acid derivatives are substrates or non-transported inhibitors of the amino
      acid transporter PAT2 (slc36a2).
AB  - The H(+)-coupled amino acid transporter PAT2 (SLC36A2) transports the amino acids
      proline, glycine, alanine and hydroxyproline. A physiological role played by PAT2
      in amino acid reabsorption in the renal proximal tubule is demonstrated by
      mutations in SLC36A2 that lead to an iminoglycinuric phenotype (imino acid and
      glycine uria) in humans. A number of proline, GABA and tryptophan derivatives
      were examined to determine if they function either as transported substrates or
      non-transported inhibitors of PAT2. The compounds were investigated following
      heterologous expression of rat PAT2 in Xenopus laevis oocytes. PAT2 function was
      characterised by: radiotracer uptake and competition (cis-inhibition) studies;
      radiotracer efflux and trans-stimulation; and measurement of substrate-induced
      positive inward current by two-electrode voltage-clamp. In general, the proline
      derivatives appeared to be transported substrates and the relative ability to
      induce current flow was closely related to the inhibitory effects on PAT2
      mediated l-[(3)H]proline uptake. In contrast, certain heterocyclic GABA
      derivatives (e.g. l-pipecolic acid) were translocated only slowly. Finally, the
      tryptophan derivatives inhibited PAT2 function but did not undergo transport. l
      Proline uptake was inhibited by 5-hydroxy-l-tryptophan (IC(50) 1.6+/-0.4mM),
      alpha-methyl-d,l-tryptophan (3.5+/-1.5mM), l-tryptophan, 1-methyl-l-tryptophan
      and indole-3-propionic acid. Although neither 5-hydroxy-l-tryptophan nor alpha
      methyl-d,l-tryptophan were able to elicit inward current in PAT2-expressing
      oocytes both reduced the current evoked by l-proline. 5-Hydroxy-l-tryptophan and
      alpha-methyl-d,l-tryptophan were unable to trans-stimulate l-proline efflux from
      PAT2-expressing oocytes, confirming that the two compounds act as non-transported
      blockers of PAT2. These two tryptophan derivatives should prove valuable
      experimental tools in future investigations of the physiological roles of PAT2.

PMID- 20691151
TI  - A novel class of photo-triggerable liposomes containing DPPC:DC(8,9)PC as
      vehicles for delivery of doxorubcin to cells.
AB  - Success of nanoparticle-mediated drug delivery is subject to development of
      optimal drug release strategies within defined space and time (triggered
      release). Recently, we reported a novel class of photo-triggerable liposomes
      prepared from dipalmitoyl phosphatidylcholine (DPPC) and photopolymerizable
      diacetylene phospholipid (DC(8),(9)PC), that efficiently released entrapped
      calcein (a water soluble fluorescent dye) upon UV (254nm) treatment. To develop
      these formulations for in vivo applications, we have examined phototriggering of
      these liposomes by visible light, and the effect of released anticancer drugs on
      cellular toxicity. Sonicated liposomes containing various ratios of
      DPPC:DC(8),(9)PC and 4mol% DSPE-PEG2000 were loaded with calcein (Ex/Em,
      485/517nm) or a chemotherapy drug, Doxorubicin (DOX, Ex/Em 490/590nm). Our
      initial experiments showed that 514nm laser treatment of liposomes containing 10
      or 20mol% DC(8,9)PC for 1-3min resulted in significant release of calcein. Based
      on these results, we performed studies with DOX-loaded liposomes. First,
      biophysical properties (including liposome size and stability) and DOX
      encapsulation efficiency of the liposomes were determined. Subsequently, the
      effect of 514nm laser on DOX release, and cellular toxicity by released DOX were
      examined. Since liposomes using the 86:10:04 mole ratio of DPPC:DC(8),(9)PC:DSPE
      PEG2000, showed highest encapsulation of DOX, these formulations were
      investigated further. We report that (i) liposomes retained about 70% of
      entrapped DOX at 37 degrees C in the presence of 0-50% serum. (ii) 514nm laser
      treatment resulted in DOX release from liposomes in a wavelength-specific manner.
      (iii) Laser treatment of co-cultures containing DOX-loaded liposomes and cells
      (Raji and MCF-7) resulted in at least 2-3 fold improved cell killing as compared
      to untreated samples. Taken together, the photo-triggerable liposomes described
      here may provide a platform for future drug delivery applications. To our
      knowledge, this is the first report demonstrating improved cell killing following
      light-triggered release of an encapsulated anticancer agent from photosensitive
      liposomes.

PMID- 20691152
TI  - Tristetraprolin controls the stability of cIAP2 mRNA through binding to the 3'UTR
      of cIAP2 mRNA.
AB  - cIAP2 is a key regulator of programmed cell death and the NF-kappaB pathway.
      Here, we investigated the post-transcriptional regulation of cIAP2 expression by
      tristetraprolin (TTP). Our results showed that overexpression of TTP reduced the
      stability of cIAP2 mRNA and the expression level of cIAP2. In addition, TTP
      destabilized a luciferase mRNA containing cIAP2 mRNA 3'UTR. cIAP2 mRNA 3'UTR
      contains four AU-rich elements (AREs) and the 2nd ARE was responsible for the TTP
      mediated destabilization of the cIAP2 mRNA. RNA EMSA revealed that TTP directly
      bound to 42 nucleotides from the 3'UTR of cIAP2 mRNA containing the 2nd ARE.
      However, the 42 nucleotides did not promote TTP-dependent destabilization of mRNA
      and did not recruit the decapping enzyme Dcp2 and the 5'-3' exonuclease Xrn1.
      When we used a 52 nucleotide sequence containing an additional 5 nucleotides from
      cIAP2 mRNA 3'UTR at both ends, this long nucleotide sequences recruited Dcp2 and
      Xrn1 and promoted TTP-dependent destabilization of mRNA. Collectively, our
      results suggest that TTP can bind to the 2nd ARE of cIAP2 mRNA 3'UTR and
      destabilize cIAP2 mRNA by forming complexes with Dcp2 and Xrn1. However, while a
      short nucleotide sequence containing the 2nd ARE of cIAP2 mRNA can recruit the
      TTP binding, this cannot recruit Dcp2 and Xrn1 and cannot induce TTP-mediated
      destabilize the mRNA. Instead, additional nucleotide sequences are required to
      recruit Dcp2 and Xrn1 and to destabilize mRNA.

PMID- 20691153
TI  - Selective destruction of mouse islet beta cells by human T lymphocytes in a newly
      established humanized type 1 diabetic model.
AB  - Type 1 diabetes (T1D) is caused by a T cell-mediated autoimmune response that
      leads to the loss of insulin-producing beta cells. The optimal preclinical
      testing of promising therapies would be aided by a humanized immune-mediated T1D
      model. We develop this model in NOD-scid IL2rgamma(null) mice. The selective
      destruction of pancreatic islet beta cells was mediated by human T lymphocytes
      after an initial trigger was supplied by the injection of irradiated spleen
      mononuclear cells (SMC) from diabetic nonobese diabetic (NOD) mice. This resulted
      in severe insulitis, a marked loss of total beta-cell mass, and other related
      phenotypes of T1D. The migration of human T cells to pancreatic islets was
      controlled by the beta cell-produced highly conserved chemokine stromal cell
      derived factor 1 (SDF-1) and its receptor C-X-C chemokine receptor (CXCR) 4, as
      demonstrated by in vivo blocking experiments using antibody to CXCR4. The
      specificity of humanized T cell-mediated immune responses against islet beta
      cells was generated by the local inflammatory microenvironment in pancreatic
      islets including human CD4(+) T cell infiltration and clonal expansion, and the
      mouse islet beta-cell-derived CD1d-mediated human iNKT activation. The selective
      destruction of mouse islet beta cells by a human T cell-mediated immune response
      in this humanized T1D model can mimic those observed in T1D patients. This model
      can provide a valuable tool for translational research into T1D.

PMID- 20691154
TI  - Testosterone affects hormone-sensitive lipase (HSL) activity and lipid metabolism
      in the left ventricle.
AB  - Fatty acids, which are the major cardiac fuel, are derived from lipid droplets
      stored in cardiomyocytes, among other sources. The heart expresses hormone
      sensitive lipase (HSL), which regulates triglycerides (TG) breakdown, and the
      enzyme is under hormonal control. Evidence obtained from adipose tissue suggests
      that testosterone regulates HSL activity. To test whether this is also true in
      the heart, we measured HSL activity in the left ventricle of sedentary male rats
      that had been treated with testosterone supplementation or orchidectomy with or
      without testosterone substitution. Left ventricle HSL activity against TG was
      significantly elevated in intact rats supplemented with testosterone. HSL
      activity against both TG and diacylglyceride was reduced by orchidectomy, whereas
      testosterone replacement fully reversed this effect. Moreover, testosterone
      increased left ventricle free fatty acid levels, caused an inhibitory effect on
      carbohydrate metabolism in the heart, and elevated left ventricular
      phosphocreatine and ATP levels as compared to control rats. These data indicate
      that testosterone is involved in cardiac HSL activity regulation which, in turn,
      may affect cardiac lipid and carbohydrate metabolism.

PMID- 20691155
TI  - Phosphorylation of the protein kinase A catalytic subunit is induced by cyclic
      AMP deficiency and physiological stresses in the fission yeast,
      Schizosaccharomyces pombe.
AB  - In the fission yeast, Schizosaccharomyces pombe, cyclic AMP (cAMP)-dependent
      protein kinase (PKA) is not essential for viability under normal culturing
      conditions, making this organism attractive for investigating mechanisms of PKA
      regulation. Here we show that S. pombe cells carrying a deletion in the adenylate
      cyclase gene, cyr1, express markedly higher levels of the PKA catalytic subunit,
      Pka1, than wild type cells. Significantly, in cyr1Delta cells, but not wild type
      cells, a substantial proportion of Pka1 protein is hyperphosphorylated. Pka1
      hyperphosphorylation is strongly induced in cyr1Delta cells, and to varying
      degrees in wild type cells, by both glucose starvation and stationary phase
      stresses, which are associated with reduced cAMP-dependent PKA activity, and by
      KCl stress, the cellular adaptation to which is dependent on PKA activity.
      Interestingly, hyperphosphorylation of Pka1 was not detected in either cyr1(+) or
      cyr1Delta S. pombe strains carrying a deletion in the PKA regulatory subunit
      gene, cgs1, under any of the tested conditions. Our results demonstrate the
      existence of a cAMP-independent mechanism of PKA catalytic subunit
      phosphorylation, which we propose could serve as a mechanism for inducing or
      maintaining specific PKA functions under conditions in which its cAMP-dependent
      activity is downregulated.

PMID- 20691156
TI  - Mitochondrial ND6 T14502C variant may modulate the phenotypic expression of LHON
      associated G11778A mutation in four Chinese families.
AB  - We report here the clinical, genetic, and molecular evaluations of four Han
      Chinese families with Leber's hereditary optic neuropathy. Thirty-one (20
      males/11 females) of 83 matrilineal relatives in these families exhibited the
      variable severity and age-at-onset in visual impairment. The average age-of-onset
      of vision loss was 22years old. Strikingly, these penetrances of visual
      impairment in these Chinese families were higher than those in other 11 Chinese
      pedigrees carrying the only ND4 G11778A mutation. Molecular analysis identified
      the known G11778A mutation and distinct sets of variants belonging to the Asian
      haplogroups M10a and M7c2. Of these, the T14502C mutation caused the substitution
      of a highly conserved isoleucine for valine at position 58 in ND6. This mutation
      has been associated with LHON in other Chinese families with very low penetrance
      of LHON. Thus, the deficient activities of complex I, caused by G11778A mutation,
      would be worsened by the T14502C mutation in these four Chinese families. As a
      result, mitochondrial dysfunctions would lead to the high penetrance and
      expressivity of visual loss in these Chinese families carrying both G11778A and
      T14502C mutations than other 11 Chinese families carrying only G11778A mutation.
      These data suggested that the T14502C variant may modulate the phenotypic
      manifestation of the G11778A mutation in these Chinese pedigrees.

PMID- 20691157
TI  - Osteogenic differentiation of mouse mesenchymal progenitor cell, Kusa-A1 is
      promoted by mammalian transcriptional repressor Rbpj.
AB  - Pluripotent mesenchymal stem cells possess the ability to differentiate into many
      cell types, but the precise mechanisms of differentiation are still unclear.
      Here, we provide evidence that Rbpj (recombination signal-binding protein for
      immunoglobulin kappa j region) protein, the primary nuclear mediator of Notch, is
      involved in osteogenesis. Overexpression of Rbpj promoted osteogenic
      differentiation of mouse Kusa-A1 cells in vitro and in vivo. Transient
      transfection of an Rbpj expression vector into Kusa-A1 cells upregulated promoter
      activities of Runx2 and Ose2. Enhanced osteogenic potentials including high
      alkaline phosphatase activity, rapid calcium deposition, and increased calcified
      nodule formation, were observed in established stable Rbpj-overexpressing Kusa-A1
      (Kusa-A1/Rbpj) cell line. In vivo mineralization by Kusa-A1/Rbpj was promoted
      compared to that by Kusa-A1 host cells. Histological findings revealed that
      expression of Rbpj was primarily observed in osteoblasts. These results suggest
      that Rbpj may play essential roles in osteoblast differentiation.

PMID- 20691158
TI  - LPS-induced NF-kappaB expression in THP-1Blue cells correlates with neopterin
      production and activity of indoleamine 2,3-dioxygenase.
AB  - Neopterin production is induced in human monocyte-derived macrophages and
      dendritic cells upon stimulation with Th1-type cytokine interferon-gamma (IFN
      gamma). In parallel, IFN-gamma induces the tryptophan-(trp)-degrading enzyme
      indoleamine 2,3-dioxygenase (IDO) and triggers the formation of reactive oxygen
      species (ROS). Translocation of the signal transduction element nuclear factor
      kappaB (NF-kappaB) is induced by ROS and accelerates the pro-inflammatory
      response by activation of other pro-inflammatory pathways. Therefore, a close
      relationship between NF-kappaB expression, the production of neopterin and the
      degradation of trp can be assumed, although this has not been demonstrated so
      far. In the present in vitro study we compared the influence of
      lipopolysaccharide (LPS) on NF-kappaB activation, neopterin formation and the
      degradation of trp in THP-1Blue cells, which represent the human myelomonocytic
      cell line THP-1 stably transfected with an NF-kappaB inducible reporter system.
      In cells stimulated with LPS, a significant induction of NF-kappaB was observed,
      and this was paralleled by an increase of kynureunine (kyn) and neopterin
      concentrations and a decline of trp. The increase of the kyn to trp quotient
      indicates accelerated IDO activity. Higher LPS concentrations and longer
      incubation of cells were associated with higher activities of all three
      biochemical pathways and significant correlations existed between NF-kappaB
      activation, neopterin release and trp degradation (all p<0.001). We conclude that
      there is a parallel induction of NF-kappaB, neopterin formation and trp
      degradation in monocytic THP-1 cells, which is elicited by pro-inflammatory
      triggers like LPS during innate immune responses.

PMID- 20691159
TI  - Neonatal mouse testis-derived multipotent germline stem cells improve the cardiac
      function of acute ischemic heart mouse model.
AB  - Multipotent germline stem (mGS) cells have been established from neonatal mouse
      testes. We previously reported that undifferentiated mGS cells are phenotypically
      similar to embryonic stem cells and that fetal liver kinase 1 (Flk1)(+) mGS cells
      have a similar potential to differentiate into cardiomyocytes and endothelial
      cells compared with Flk1(+) embryonic stem cells. Here, we transplanted these
      Flk1(+) mGS cells into an ischemic heart failure mouse model to evaluate the
      improvement in cardiac function. Significant increase in left ventricular wall
      thickness of the infarct area, left ventricular ejection fraction and left
      ventricular maximum systolic velocity was observed 4weeks after when sorted
      Flk1(+) mGS cells were transplanted directly into the hearts of the acute
      ischemic model mice. Although the number of cardiomyocytes derived from Flk1(+)
      mGS cells were too small to account for the improvement in cardiac function but
      angiogenesis around ischemic area was enhanced in the Flk1(+) mGS cells
      transplanted group than the control group and senescence was also remarkably
      diminished in the early phase of ischemia according to beta-galactosidase
      staining assay. In conclusion, Flk1(+) mGS cell transplantation can improve the
      cardiac function of ischemic hearts by promoting angiogenesis and by delaying
      host cell death via senescence.

PMID- 20691160
TI  - ER regulates an evolutionarily conserved apoptosis pathway.
AB  - Estrogen receptor (ER) is regarded as a major causal factor in breast cancer and
      FoxA1, a winged-helix transcription factor belonging to the forkhead family, has
      been found to function as a pioneer factor in the recruitment of ER to several
      cis-regulatory elements in the genome. High throughput chromatin
      immunoprecipitation analyzed by hybridization to microarrays (ChIP-chip) can
      reveal ER and FoxA1 binding sites occupied by transcription factors. However,
      these results are blind to lineage-specific cis-regulatory elements. In this
      study, we identified ER and FoxA1 binding sites conserved in evolution by using
      Detection of LinEage-Specific Selection (DLESS) method. We also analyzed target
      genes close to conserved cis-regulatory elements by combining gene-expression
      data. A total of 7877 ER binding sites and 18,135 FoxA1 binding sites were
      identified in MCF-7 cells by performing an unbiased genome-wide ChIP-chip with
      False Discovery Rate (FDR) of 5%. Using DLESS method, we found target candidate
      genes closest to fully conserved cis-regulatory elements related to apoptosis
      according to gene ontology analysis. Furthermore, network analysis of apoptosis
      related genes within 10 kb of fully conserved cis-regulatory elements was
      constructed using Ingenuity Pathway Analysis (IPA). Apoptosis genes in the
      network showed over- and under-expression in MCF-7 cell-line. And these apoptosis
      related genes closest to fully conserved cis-regulatory elements in network
      showed strong correlation with ER in MCF-7 cells. These results elucidate that ER
      regulates an evolutionarily conserved apoptosis pathway. This opens up new
      perspectives in the apoptosis of human breast cancer from the evolution of cis
      regulatory elements.

PMID- 20691161
TI  - Regulation of neural progenitor cell fate by anandamide.
AB  - Exogenous application of neural progenitor cells (NPCs) has successful
      implications in treating brain disorders, and research is beginning to identify
      ways to mimic this exogenous application by activating endogenous stem cell
      compartments. The recent discovery of a functional endocannabinoid system in
      murine NPCs (mNPCs) represents one potential therapeutic means to influence
      endogenous stem cell compartments. High levels of the endogenous cannabinoids
      anandamide (AEA) and 2-arachidonoylglycerol (2-AG) persist during CNS
      inflammation and infection. The goal of this study was to assess the influence of
      AEA on mNPCs to identify how the endocannabinoid system influences mNPCs in
      vitro, a potential model to investigate effects of endocannabinoids on endogenous
      stem cell compartments. Our results show that AEA affects mNPC cell fate
      determination. Initial glial differentiation was observed, followed by induction
      of neuronal differentiation with AEA treatment. Cell survival and apoptosis was
      not affected by AEA. These effects were coupled by an increased phosphorylation
      of cAMP-responsive element (CRE) binding protein (CREB).

PMID- 20691162
TI  - Indoxyl sulfate, a uremic toxin, promotes cell senescence in aorta of
      hypertensive rats.
AB  - We demonstrated that administration of indoxyl sulfate, a uremic toxin, promotes
      aortic calcification in hypertensive rats. This study aimed to clarify if indoxyl
      sulfate could contribute to cell senescence in the aorta of hypertensive rats.
      The rat groups consisted of (1) Dahl salt-resistant normotensive rats (DN), (2)
      Dahl salt-resistant normotensive indoxyl sulfate-administered rats (DN+IS), (3)
      Dahl salt-sensitive hypertensive rats (DH), and (4) Dahl salt-sensitive
      hypertensive indoxyl sulfate-administered rats (DH+IS). After 32weeks, their
      arcuate aortas were excised for histological and immunohistochemical analysis.
      Cell senescence was evaluated by immunohistochemistry of senescence-associated
      beta-galactosidase (SA-beta-gal), and senescence-related proteins such as
      p16(INK4a), p21(WAF1/CIP1), p53 and retinoblastoma protein (Rb). Both DH and
      DH+IS rats showed significantly higher systolic blood pressure than DN and DN+IS
      rats, respectively. Serum indoxyl sulfate levels were significantly higher in
      DN+IS and DH+IS rats than in DN and DH rats, respectively. In aorta, DH rats
      showed significantly increased aortic calcification and wall thickness, and
      increased expression of SA-beta-gal, p16(INK4a), p21(WAF1/CIP1), p53 and Rb in
      the calcification area of arcuate aorta as compared with DN rats. More notably,
      DH+IS rats showed significantly increased aortic calcification and wall
      thickness, and significantly increased expression of SA-beta-gal, p16(INK4a),
      p21(WAF1/CIP1), p53 and Rb in the cells embedded in the calcification area as
      compared with DH rats. In conclusion, indoxyl sulfate promotes cell senescence
      with aortic calcification and expression of senescence-related proteins in
      hypertensive rats.

PMID- 20691164
TI  - Chain-dependent photocytotoxicity of tricationic porphyrin conjugates and related
      mechanisms of cell death in proliferating human skin keratinocytes.
AB  - Photodynamic therapy (PDT) is a poor treatment option for nodular basal cell
      carcinomas and squamous cell carcinomas. As a result, the search for new
      photosensitizers with better effectiveness is of current interest. The
      photocytotoxicity of conjugates (P-R) of a water-soluble tri-cationic porphyrin
      (P-H) having similar efficiency of production of singlet oxygen, the PDT
      cytotoxin, has been assessed in vitro. Links between uptake, intracellular
      localization, photooxidative stress, photocytotoxicity and ability to induce
      programmed cell death are established. Conjugates bearing methyl (P-Me), Di-O
      isopropylidene-(-d-galactopyranosyl (P-OGal) or N,N'
      dicyclohexylureidooxycarbonyl (P-DDC) chains are efficiently taken-up by
      proliferating NCTC 2544 keratinocytes. The relative order of photocytotoxicity is
      P-OGal >P-DDC=P-Me?P-H. The photocytotoxic potential of P-Me, P-OGal and P-DDC
      equals that of endogenous protoporphyrin IX induced by delta-aminolevulinic acid
      or its esters, the pro-drugs currently employed for PDT of skin lesions.
      Microfluorometry shows that P-Me, P-OGal, and P-DDC localize in endocytotic or
      pinocytotic vesicles but not in mitochondria or nucleus. Absence of annexin V
      binding, caspase activation or chromatin condensation suggests that cell
      photosensitization by P-R does not induce apoptosis. On the other hand, P-OGal
      photocytotoxicity correlates with appearance of multiple vesicles that have
      hallmarks of autophagy compartments, being decorated with the marker LC3 in cells
      transfected with an expression vector encoding GFP-LC3. p38 and JNK
      phosphorylation and inhibition of ERK1/2 phosphorylation suggest close
      relationship between mortality of NCTC 2544 keratinocytes and MAPK pathway
      impairment. Given their potentially easy formulation, water-soluble P-R are
      promising powerful photosensitizers for PDT of skin lesions.

PMID- 20691163
TI  - The Ski protein negatively regulates Siah2-mediated HDAC3 degradation.
AB  - Ski acts as a transcriptional co-repressor by multiple direct and indirect
      interactions with several distinct repression complexes. Ski represses retinoic
      acid (RA) signaling by interacting with, and stabilizing, key components of the
      co-repressor complex, namely, HDAC3. However, little is known as to how the Ski
      protein can stabilize HDAC3. In the present study, we identified the Siah2
      protein as a potential E3 ubiquitin ligase that mediated proteasomal degradation
      of HDAC3. Reciprocal co-immunoprecipitation assays further revealed that Ski
      interacts with Siah2. Furthermore, co-expression of the Ski protein stabilized
      the level of Siah2 protein. Since Siah2 regulates its own level of expression by
      self-degradation, the stabilization of Siah2 by Ski is an indication that Ski
      association leads to inhibition of Siah2 E3 ubiquitin ligase activity. Only wild
      type Ski and Ski truncation mutants that were in the same complex with Siah2
      could stabilize HDAC3 levels. Taken together, the results suggest that
      association with Ski leads to inhibition of Siah2 E3 ubiquitin ligase activity
      and in this way, the Ski protein inhibits Siah2-mediated proteasomal degradation
      of HDAC3.

PMID- 20691165
TI  - Eicosapentaenoic acid improves hepatic steatosis independent of PPARalpha
      activation through inhibition of SREBP-1 maturation in mice.
AB  - Eicosapentaenoic acid (EPA) in fish oil is known to improve hepatic steatosis.
      However, it remains unclear whether such action of EPA is actually caused by
      peroxisome proliferator-activated receptor alpha (PPARalpha) activation. To
      explore the contribution of PPARalpha to the effects of EPA itself, male wild
      type and Ppara-null mice were fed a saturated fat diet for 16 weeks, and highly
      (>98%)-purified EPA was administered in the last 12 weeks. Furthermore, the
      changes caused by EPA treatment were compared to those elicited by fenofibrate
      (FF), a typical PPARalpha activator. A saturated fat diet caused macrovesicular
      steatosis in both genotypes. However, EPA ameliorated steatosis only in wild-type
      mice without PPARalpha activation, which was evidently different from numerous
      previous observations. Instead, EPA inhibited maturation of sterol-responsive
      element-binding protein (SREBP)-1 in the presence of PPARalpha through down
      regulation of SREBP cleavage-activating protein and site-1 protease.
      Additionally, EPA suppressed fatty acid uptake and promoted hydrolysis of
      intrahepatic triglycerides in a PPARalpha-independent manner. These effects were
      distinct from those of fenofibrate. Although fenofibrate induced NAPDH oxidase
      and acyl-coenzyme A oxidase and significantly increased hepatic lipid peroxides,
      EPA caused PPARalpha-dependent induction of superoxide dismutases, probably
      contributing to a decrease in the lipid peroxides. These results firstly
      demonstrate detailed mechanisms of steatosis-ameliorating effects of EPA without
      PPARalpha activation and ensuing augmentation of hepatic oxidative stress.

PMID- 20691167
TI  - Purkinje cell number decreases in the adult female rat cerebellum following
      exposure to 900 MHz electromagnetic field.
AB  - The biological effects of electromagnetic field (EMF) exposure from mobile phones
      have growing concern among scientists since there are some reports showing
      increased risk for human health, especially in the use of mobile phones for a
      long duration. In the presented study, the effects on the number of Purkinje
      cells in the cerebellum of 16-week (16 weeks) old female rats were investigated
      following exposure to 900 MHz EMF. Three groups of rats, a control group (CG),
      sham exposed group (SG) and an electromagnetic field exposed group (EMFG) were
      used in this study. While EMFG group rats were exposed to 900 MHz EMF (1h/day for
      28 days) in an exposure tube, SG was placed in the exposure tube but not exposed
      to EMF (1h/day for 28 days). The specific energy absorption rate (SAR) varied
      between 0.016 (whole body) and 2 W/kg (locally in the head). The CG was not
      placed into the exposure tube nor was it exposed to EMF during the study period.
      At the end of the experiment, all of the female rats were sacrificed and the
      number of Purkinje cells was estimated using a stereological counting technique.
      Histopathological evaluations were also done on sections of the cerebellum.
      Results showed that the total number of Purkinje cells in the cerebellum of the
      EMFG was significantly lower than those of CG (p<0.004) and SG (p<0.002). In
      addition, there was no significant difference at the 0.05 level between the rats'
      body and brain weights in the EMFG and CG or SG. Therefore, it is suggested that
      long duration exposure to 900 MHz EMF leads to decreases of Purkinje cell numbers
      in the female rat cerebellum.

PMID- 20691168
TI  - Effects of resveratrol on membrane biophysical properties: relevance for its
      pharmacological effects.
AB  - The current study gathers a range of spectrophotometric and spectrofluorimetric
      techniques to systematically monitor the effects of resveratrol (trans-3,5,4'
      trihydrostilbene) on the biophysical properties of membrane model systems
      consisting of unilamellar liposomes of phosphatidylcholine (DPPC) with the
      ultimate goal of relating these effects with some of the well documented
      pharmacological properties of this compound, and clarifying some controversial
      results reported on the literature. Physiological conditions have been pursued,
      such as a buffered pH control with adjusted ionic strength similar to the blood
      plasma conditions (pH 7.4, I=0.1M) and the study at different membrane physical
      states (gel phase and fluid phase) for the assessment of resveratrol-membrane:
      aqueous partition coefficient by derivative spectroscopy. Results obtained by
      fluorescence quenching and anisotropy studies indicate that resveratrol has a
      membrane fluidizing effect and is able to permeate the membrane even in the gel
      phase. These results mirror the well described antioxidant effect of resveratrol,
      since antioxidants have to reach peroxidised rigid membranes and increase
      membrane fluidity in order to interact more efficiently with lipid radicals in
      the disordered lipid bilayer. Location of resveratrol pointed also to a membrane
      distribution that is favourable for scavenging the lipid radicals and was
      elucidated using probes positioned at different membrane depths suggesting that
      this compound penetrates into the acyl membrane region but also positions its
      polar hydroxyl group near the headgroup region of the membrane.

PMID- 20691166
TI  - Co-localization of TRHR1 and LepRb receptors on neurons in the hindbrain of the
      rat.
AB  - We have reported a highly cooperative interaction between leptin and thyrotropin
      releasing hormone (TRH) in the hindbrain to generate thermogenic responses
      (Hermann et al., 2006) (Rogers et al., 2009). Identifying the locus in the
      hindbrain where leptin and TRH act synergistically to increase thermogenesis will
      be necessary before we can determine the mechanism(s) by which this interaction
      occurs. Here, we performed heat-induced epitope recovery techniques and in situ
      hybridization to determine if neurons or afferent fibers in the hindbrain possess
      both TRH type 1 receptor and long-form leptin receptor [TRHR1; LepRb,
      respectively]. LepRb receptors were highly expressed in the solitary nucleus
      [NST], dorsal motor nucleus of the vagus [DMN] and catecholaminergic neurons of
      the ventrolateral medulla [VLM]. All neurons that contained LepRb also contained
      TRHR1. Fibers in the NST and the raphe pallidus [RP] and obscurrus [RO] that
      possess LepRb receptors were phenotypically identified as glutamatergic type 2
      fibers (vglut2). Fibers in the NST and RP that possess TRHR1 receptors were
      phenotypically identified as serotonergic [i.e., immunopositive for the serotonin
      transporter; SERT]. Co-localization of LepRb and TRHR1 was not observed on
      individual fibers in the hindbrain but these two fiber types co-mingle in these
      nuclei. These anatomical arrangements may provide a basis for the synergy between
      leptin and TRH to increase thermogenesis.

PMID- 20691169
TI  - Cardiac multi-marker strategy for effective diagnosis of acute myocardial
      infarction.
AB  - BACKGROUND: Heart-type fatty acid-binding protein (H-FABP) is a heart-specific
      and highly sensitive biomarker for early diagnosis of acute myocardial infarction
      (AMI). We investigated the effectiveness of H-FABP for diagnosis of AMI in
      patients with different ethnic background and different time from symptom onset.
      METHODS: Venous blood was withdrawn from consecutive patients with acute chest
      pain admitted to the First Affiliated Hospital of Xinjiang Medical University.
      The blood samples were used for measurement of creatine kinase MB (CK-MB) and
      cardiac troponin I (cTnI) using Beckman Coulter DC-800 analyzer, and detection of
      H-FABP using a one-step bedside immunotest. RESULTS: Two hundred and eighty-nine
      patients admitted within 12h after the onset of symptoms were recruited in the
      study. The H-FABP immunotest was found to have higher diagnostic accuracy than
      cTnI and CK-MB in patients admitted within 3h. The combination of H-FABP and cTnI
      was found to have the highest diagnostic accuracy (91%) among different cardiac
      markers and the other combinations. It gave the highest sensitivity [96% (95% CI:
      91-98%)] and a comparable specificity [84% (95% CI: 76-89%)] to cTnI alone.
      CONCLUSION: A cardiac panel consisting of H-FABP and troponin is recommended.

PMID- 20691170
TI  - Acquired Pelger-Huet: what does it really mean?
AB  - Pelger-Huet anomaly (PHA) is a benign inherited condition characterized by
      hyposegmentation of the neutrophil's nucleus and excessive chromatin clumping. An
      acquired neutrophil dysplasia similar to PHA has been described in hematological
      diseases and in some clinical conditions. It has been known as acquired or pseudo
      PHA. Although some hypotheses have been proposed to explain this phenomenon, the
      mechanism of nuclear change is still unclear. Only the laboratory and clinical
      data combined will yield a better understanding on the need for follow-up and
      management of patients in the appropriate cases. In addition, a possible cause of
      pseudo PHA must always be investigated to add insights to the full understanding
      of this abnormality. Whether this neutrophil phenomenon has clinical implications
      remains to be elucidated. It is clear that only a small number of patients under
      drugs (immunosuppressive and others) may present these neutrophil abnormalities.
      Most of them do not show this phenomenon and we are unable to explain the
      different responses in drug users. Whether these patients display a
      predisposition for developing bone marrow or other diseases in the future, it is
      a very intriguing matter and only a follow-up will solve this question.

PMID- 20691171
TI  - Malondialdehyde (MDA) and protein carbonyl (PCO) levels as biomarkers of
      oxidative stress in subjects with familial hypercholesterolemia.
AB  - OBJECTIVE: Familial hypercholesterolemia (FH) is clinically characterized by
      elevated total and low-density lipoprotein (LDL) cholesterol levels in plasma,
      which has high risk for developing atherosclerosis. Increased oxidative stress
      (OS) and FH have been related to atherosclerosis. The study aims to evaluate
      oxidative stress in patients with hypercholesterolemia by measuring lipid
      peroxidation and protein carbonyl (PCO) levels in these patients. PCO in these
      patients may provide a new diagnostic biomarker for oxidative damage in
      atherosclerosis. DESIGN AND METHOD: Total cholesterol (Tc), low-density
      lipoprotein-cholesterol (LDL-c), triglyceride (TG), high-density lipoprotein
      cholesterol (HDL-c), lipoprotein(a) (Lp-a) levels and carotid intima-media
      thickness were measured to evaluate characteristics of patients (11 homozygous
      and 25 heterozygous) with FH. 25 age-gender-BMI matched healthy control subjects
      were included in the study for comparison. RESULTS: MDA and PCO levels were
      significantly higher in homozygous patients compared with those of heterozygous
      and controls and it was found that they are positively correlated with LDL-c, Tc,
      Lp-a and IMT while negatively correlated with HDL-c. The heterozygous group also
      had significantly higher MDA and PCO levels compared with controls. CONCLUSION:
      The data obtained could be important for understanding the alterations presented
      by FH and could be related to their increased risk of developing atherosclerosis.
      To our knowledge, measurements of PCO in patients with FH are not recorded before
      and this may be used as a biomarker for protein oxidation, which may play a role
      in the increased cardiovascular risk of patients with FH.

PMID- 20691172
TI  - A multi-target screening analysis in human plasma using fast liquid
      chromatography-hybrid tandem mass spectrometry (Part I).
AB  - OBJECTIVES: Evaluate a new LC-MS/MS screening method for drugs and drugs of abuse
      as an alternative to the existing methods used in clinical toxicology
      laboratories. DESIGN AND METHODS: The work was divided in two parts. The first
      part was dedicated to the technical development and evaluation of the method for
      which a set of 97 drugs and relevant metabolites was used to perform a complete
      investigation of matrix effects and lower limit of identification (LOI). The
      second part was a comparison of identified drugs between LC-MS/MS and Remedi(r)
      instrument on clinical serum samples. RESULTS: The method offers good performance
      allowing an automatic peak detection and compound identification. The limit of
      identification is equivalent to 50 MUg/L for the majority of the studied
      compounds. The process efficiency (PE) is higher than 70% for 65% of the
      evaluated compounds. Thus, a sufficient detection capability in terms of limit of
      detection for identification and PE satisfied the expected performance.
      CONCLUSION: The described methodology allows the identification of the main drugs
      incriminated in intoxications within a quite short analysis time. The separation
      of most of the analytes is performed in 15 min. The procedure is sufficiently
      sensitive and selective.

PMID- 20691173
TI  - Serum gamma-glutamyltransferase fractions in myotonic dystrophy type I:
      differences with healthy subjects and patients with liver disease.
AB  - OBJECTIVES: Elevation of serum gamma-glutamyltransferase (GGT), in absence of a
      clinically significant liver damage, is often found in Myotonic Dystrophy type-1
      (DM1). In this study we investigated if a specific GGT fraction pattern is
      present in DM1. DESIGNS AND METHODS: We compared total and fractional GGT values
      (b-, m-, s-, f-GGT) among patients with DM1 or liver disease (LD) and healthy
      subjects (HS). RESULTS: The increase of GGT in DM1 and LD, vs HS, was mainly due
      to s-GGT (median: 32.7; 66.7; and 7.9 U/L, respectively), and b-GGT (8.5; 18.9;
      and 2.1 U/L). The subset of DM1 patients matched with HS with corresponding serum
      GGT showed higher b-GGT (6.0 vs 4.2 U/L). CONCLUSIONS: DM1 patients with normal
      total GGT values showed an alteration of the production and release in the blood
      of GGT fractions. Since increased s-GGT is also found in LD, a sub-clinical liver
      damage likely occurs in DM1 subjects apparently free of liver disease.

PMID- 20691174
TI  - Thyroid hormone testing by tandem mass spectrometry.
AB  - In the euthyroid person, absolute free thyroxine concentrations remain constant
      and correlate with the tissue hormone level, its biologic effect and the
      metabolic status of the patient. However, most circulating thyroid hormone is
      bound to plasma proteins and only a minute amount is in the unbound free form.
      Studies have shown that current free thyroxine immunoassays are binding protein
      dependent. Novel high-performance liquid chromatography tandem mass spectrometry
      (LC/MS/MS) methods have successfully dealt with problems inherent in many
      immunoassays for thyroid hormones and afforded improved specificity and accuracy
      in thyroid hormone measurements. We emphasize problems with thyroid hormone
      testing employing immunoassays including direct and indirect thyroid hormone
      immunoassays, sample processing, methods of free hormone separation and review
      the emerging role of liquid chromatography-tandem mass spectrometry in thyroid
      hormone testing. The latest generation of tandem mass spectrometers has superior
      limits of quantification, permitting omission of previously employed
      derivatization steps. Liquid chromatography-tandem mass spectrometry affords the
      specificity, precision, and limits of quantification necessary for the reliable
      measurement of thyroid hormones, enhancing diagnostic capabilities, and affording
      the profiles of the iodothyronines and thyronamines. These methods are especially
      important in states of disease and during pregnancy when protein binding is a
      factor that interferes with other methods for thyroid hormone analysis.

PMID- 20691175
TI  - C. elegans twist gene expression in differentiated cell types is controlled by
      autoregulation through intron elements.
AB  - The temporospatial regulation of genes encoding transcription factors is
      important during development. The hlh-8 gene encodes the C. elegans mesodermal
      transcription factor CeTwist. Elements in the hlh-8 promoter restrict gene
      expression to predominantly undifferentiated cells of the M lineage. We have
      discovered that hlh-8 expression in differentiated mesodermal cells is controlled
      by two well-conserved E box elements in the large first intron. Additionally, we
      found that these elements are bound in vitro by CeTwist and its transcription
      factor partner, CeE/DA. The E box driven expression is eliminated or diminished
      in an hlh-8 null allele or in hlh-2 (CeE/DA) RNAi, respectively. Expression of
      hlh-8 is also diminished in animals harboring an hlh-8 intron deletion allele.
      Altogether, our results support a model in which hlh-8 is initially expressed in
      the undifferentiated M lineage cells via promoter elements and then the CeTwist
      activates its own expression further (autoregulation) in differentiated cells
      derived from the M lineage via the intron elements. This model provides a
      mechanism for how a transcription factor may regulate distinct target genes in
      cells both before and after initiating the differentiation program. The findings
      could also be relevant to understanding human Twist gene regulation, which is
      currently not well understood.

PMID- 20691176
TI  - Mouse atonal homolog 1 directs intestinal progenitors to secretory cell rather
      than absorptive cell fate.
AB  - The Notch-regulated transcription factor mouse atonal homolog 1 (Math1) is
      required for the development of intestinal secretory cells, as demonstrated by
      the loss of goblet, endocrine and Paneth cell types in null mice. However, it was
      unknown whether Math1 is sufficient to induce the program of secretory cell
      differentiation. To examine the function of Math1 in the differentiation of
      intestinal epithelial cells, intestinal morphology and epithelial and mesenchymal
      cell fate were examined by histological staining and marker gene expression in
      transgenic mice expressing a villin-regulated Math1 transgene. Late prenatal
      transgenic founders exhibited a gross cellular transformation into a secretory
      epithelium. The expansion of secretory cells coupled with the almost complete
      loss of absorptive enterocytes suggested reprogramming of a bipotential
      progenitor cell. Moreover, Math1 expression inhibited epithelial cell
      proliferation, as demonstrated by a marked reduction in Ki67 positive cells and
      blunted villi. Unexpectedly, the transgenic mesenchyme was greatly expanded with
      increased proliferation. Several mesenchymal cell types were amplified, including
      smooth muscle and neurons, with maintenance of basic radial patterning. Since
      transgenic Math1 expression was restricted to the epithelium, these findings
      suggest that epithelial-mesenchymal signaling is altered by the cellular changes
      induced by Math1. Thus, Math1 is a key effector directing multipotential
      precursors to adopt secretory and not absorptive cell fate.

PMID- 20691177
TI  - Drosophila Cand1 regulates Cullin3-dependent E3 ligases by affecting the
      neddylation of Cullin3 and by controlling the stability of Cullin3 and adaptor
      protein.
AB  - Cullin-RING ubiquitin ligases (CRLs), which comprise the largest class of E3
      ligases, regulate diverse cellular processes by targeting numerous proteins.
      Conjugation of the ubiquitin-like protein Nedd8 with Cullin activates CRLs.
      Cullin-associated and neddylation-dissociated 1 (Cand1) is known to negatively
      regulate CRL activity by sequestering unneddylated Cullin1 (Cul1) in biochemical
      studies. However, genetic studies of Arabidopsis have shown that Cand1 is
      required for optimal CRL activity. To elucidate the regulation of CRLs by Cand1,
      we analyzed a Cand1 mutant in Drosophila. Loss of Cand1 causes accumulation of
      neddylated Cullin3 (Cul3) and stabilizes the Cul3 adaptor protein HIB. In
      addition, the Cand1 mutation stimulates protein degradation of Cubitus
      interruptus (Ci), suggesting that Cul3-RING ligase activity is enhanced by the
      loss of Cand1. However, the loss of Cand1 fails to repress the accumulation of Ci
      in Nedd8(AN015) or CSN5(null) mutant clones. Although Cand1 is able to bind both
      Cul1 and Cul3, mutation of Cand1 suppresses only the accumulation of Cul3 induced
      by the dAPP-BP1 mutation defective in the neddylation pathway, and this effect is
      attenuated by inhibition of proteasome function. Furthermore, overexpression of
      Cand1 stabilizes the Cul3 protein when the neddylation pathway is partially
      suppressed. These data indicate that Cand1 stabilizes unneddylated Cul3 by
      preventing proteasomal degradation. Here, we propose that binding of Cand1 to
      unneddylated Cul3 causes a shift in the equilibrium away from the neddylation of
      Cul3 that is required for the degradation of substrate by CRLs, and protects
      unneddylated Cul3 from proteasomal degradation. Cand1 regulates Cul3-mediated E3
      ligase activity not only by acting on the neddylation of Cul3, but also by
      controlling the stability of the adaptor protein and unneddylated Cul3.

PMID- 20691178
TI  - Genetic manipulation of individual somatic mammary cells in vivo reveals a master
      role of STAT5a in inducing alveolar fate commitment and lactogenesis even in the
      absence of ovarian hormones.
AB  - Assessing the molecular control of development and cell fate in individual cells
      in the intact mammary epithelium has not been possible to date. By exploiting an
      intraductal retrovirus (RCAS)-mediated gene delivery method to introduce a marker
      gene, we found that ductal epithelial cells are turned over with a half time of
      approximately 1month in adult virgin mice. However, following RCAS-mediated
      introduction of a constitutively activated STAT5a (caSTAT5a), caSTAT5a-activated
      ductal epithelial cells expand and replace other cells in the epithelium,
      eventually forming a mammary gland resembling that in a late pregnant mouse,
      suggesting that STAT5a activation alone is sufficient to mediate pregnancy
      induced mammary cell expansion, alveolar cell fate commitment, and lactogenesis.
      Furthermore, such caSTAT5a-induced alveolar differentiation does not require
      ovarian functions, although caSTAT5a-induced cell proliferation is partly reduced
      in ovariectomized mice. In conclusion, in this first report of studying the
      developmental role of a gene in a few cells in a normally developed virgin
      mammary ductal tree, STAT5a activation causes alveolar fate commitment and
      lactogenesis, and with the help of ovarian hormones, drives alveolar expansion.

PMID- 20691179
TI  - Berberine induces apoptosis in breast cancer cells (MCF-7) through mitochondrial
      dependent pathway.
AB  - Bioactive compounds found in many plant species have been used in Chinese, Unani,
      and Indian ayurvedic medicine. Accumulative evidences in both in vitro and in
      vivo studies using berberine demonstrated anti-cancer and anti-inflammatory
      properties in different cancer cells. In the present study, a putative compound
      from commercial sample was purified by chromatographic techniques. The structure
      of the pure compound was confirmed by spectroscopic studies. The purified
      berberine was tested against breast cancer (MCF-7) and normal human breast
      epithelial (MCF-12F) cells for 24, 48 and 72 h at various concentrations. Using
      MTT assay, berberine exhibited a significant cytotoxic effect on the MCF-7 cells
      (P<0.01) without affecting the breast normal epithelial cell growth at 25 microM
      concentration. Based on these results, MCF-7 cells were treated with 25 microM
      berberine for 48 and 72 h for further studies to illustrate induction of
      apoptosis through cell cycle distribution and DNA fragmentation with agarose gel
      electrophoresis. Western blotting with treated cells revealed that berberine
      induces apoptosis in MCF-7 cells through a mitochondria-dependent pathway by
      increasing levels of cytoplasmic cytochrome c, caspase-9 activity and cleavage of
      PARP while decreasing levels of Bcl-2. Furthermore, immunoblotting results
      demonstrated that p53 and p27 were up-regulated suggesting that barberine seems
      to play a pro-apoptotic role in cancer cells. In conclusion, berberine inhibits
      the proliferation of MCF-7 breast cancer cells through a mitochondria and caspase
      dependent apoptotic pathway. It is possible that berberine may serve as a
      potential naturally occurring compound for breast cancer therapy.

PMID- 20691180
TI  - Mitochondrial dysfunction in glaucoma and emerging bioenergetic therapies.
AB  - The similarities between glaucoma and mitochondrial optic neuropathies have
      driven a growing interest in exploring mitochondrial function in glaucoma. The
      specific loss of retinal ganglion cells is a common feature of mitochondrial
      diseases - not only the classic mitochondrial optic neuropathies of Leber's
      Hereditary Optic Neuropathy and Autosomal Dominant Optic Atrophy - but also
      occurring together with more severe central nervous system involvement in many
      other syndromic mitochondrial diseases. The retinal ganglion cell, due to
      peculiar structural and energetic constraints, appears acutely susceptible to
      mitochondrial dysfunction. Mitochondrial function is also well known to decline
      with aging in post-mitotic tissues including neurons. Because age is a risk
      factor for glaucoma this adds another impetus to investigating mitochondria in
      this common and heterogeneous neurodegenerative disease. Mitochondrial function
      may be impaired by either nuclear gene or mitochondrial DNA genetic risk factors,
      by mechanical stress or chronic hypoperfusion consequent to the commonly raised
      intraocular pressure in glaucomatous eyes, or by toxic xenobiotic or even light
      induced oxidative stress. If primary or secondary mitochondrial dysfunction is
      further established as contributing to glaucoma pathogenesis, emerging therapies
      aimed at optimizing mitochondrial function represent potentially exciting new
      clinical treatments that may slow retinal ganglion cell and vision loss in
      glaucoma.

PMID- 20691181
TI  - Taenia solium: immune response against oral or systemic immunization with
      purified recombinant calreticulin in mice.
AB  - Recombinant functional Taenia solium calreticulin (rTsCRT) confers different
      degrees of protection in the experimental model of intestinal taeniosis in
      hamsters. The aim of this study was to evaluate the immune response induced after
      oral or systemic immunization with an electroeluted rTsCRT in BALB/c mice. Oral
      immunization elicited high fecal IgA and the production of IL-4 and IL-5 by
      mesenteric lymph node cells after in vitro stimulation with rTSCRT, indicating a
      Th2 response. Mice subcutaneously immunized produced high amounts of serum IgG,
      being IgG1 (Th2-related) the predominant isotype, while in vitro stimulated
      spleen cells synthesized IL-4, IL-5 and also IFN-gamma, indicating a mixed
      Th1/Th2 cellular response after systemic immunization. Our data show that
      purified rTsCRT induces polarized Th2 responses after oral immunization of mice,
      a common characteristic of protective immunity against helminths and,
      consequently, a desirable hallmark in the search for a vaccine.

PMID- 20691182
TI  - Entamoeba invadens: identification of ADF/cofilin and their expression analysis
      in relation to encystation and excystation.
AB  - The differentiation processes of excystation and encystation of Entamoeba are
      essential for infection and completion of their life-cycle, and the processes
      need cell motility and its control by actin cytoskeletal reorganization. This
      study investigated actin depolymerizing factor (ADF)/cofilin (Cfl) family
      proteins, which are important molecules in actin cytoskeletal reorganization, in
      Entamoeba invadens in relation to the encystation and excystation. Axenic culture
      systems were used to induce encystation and excystation. A homology search of the
      E. invadens genome database and molecular cloning identified three ADF/Cfl family
      proteins of the parasite (named for short as EiCfl-1, EiCfl-2, and EiCfl-3). This
      is different from other Entamoeba species, i.e. Entamoeba histolytica and
      Entamoeba dispar, each of which has only one ADF/Cfl family protein. These
      ADF/Cfl of E. invadens do not have Ser3 (serine locates third from first
      methionine), similar to E. histolytica, E. dispar, Saccharomyces cerevisiae and
      Schizosaccharomyces pombe, although the activity of ADF/Cfl is negatively
      regulated by phosphorylation of the Ser3 in metazoans. Phylogenetic analysis
      revealed that Entamoeba Cfl formed a distinctive clade that is separate from
      other organisms, and the branches of the tree were separated in two consistent
      with the presence and absence of Ser3. Rabbit anti-EiCfl-2 serum reacted with all
      recombinant EiCfls and EiCfl in lysates of cysts, trophozoites and metacystic
      amoebae. Immunofluorescence staining with this antiserum showed co-localization
      of EiCfl with actin beneath the cell membrane through the life stages. Both
      proteins proved to be rich in pseudopodia of trophozoites and metacystic amoebae.
      Real-time RT-PCR showed that mRNAs of EiCfl-2 and actins were highly expressed,
      but there were few mRNA of EiCfl-1 and EiCfl-3. Remarkably decreased mRNA levels
      were observed in EiCfl-2 and actins during encystation. All three EiCfls and
      actins became transcribed after the induction of excystation. The mRNAs of only
      EiCfl-1 and EiCfl-3 increased remarkably when the excystation was induced in the
      presence of cytochalasin D. These findings demonstrate that EiCfl-2 and actins co
      localize beneath the cell membrane in trophozoites and cysts as well as
      metacystic amoebae being rich in pseudopodia, that EiCfl-1 and EiCfl-3 are
      expressed only after the induction of excystation, and that enhanced excystation
      by cytochalasin D is associated with high expression of EiCfl-1 and EiCfl-3.

PMID- 20691184
TI  - Protons released during pancreatic acinar cell secretion acidify the lumen and
      contribute to pancreatitis in mice.
AB  - BACKGROUND & AIMS: Secretory granules are acidic; cell secretion will therefore
      lead to extracellular acidification. We propose that during secretion, protons co
      released with proteins from secretory granules of pancreatic acinar cells acidify
      the restricted extracellular space of the pancreatic lumen to regulate normal
      physiological and pathophysiological functions in this organ METHODS:
      Extracellular changes in pH were quantified in real time using 2-photon
      microscopy analysis of pancreatic tissue fragments from mouse models of acute
      pancreatitis (mice given physiological concentrations [10 -20 pM] of
      cholecystokinin or high concentrations of [100 nM] cerulein). The effects of
      extracellular changes in pH on cell behavior and structures were measured.
      RESULTS: With physiological stimulation, secretory granule fusion (exocytosis)
      caused acidification of the pancreatic lumen. Acidifications specifically
      affected intracellular calcium responses and accelerated the rate of recovery
      from agonist-evoked calcium signals. Protons therefore appear to function as
      negative-feedback, extracellular messengers during coupling of cell stimuli with
      secretion. At high concentrations of cerulein, large increases in secretory
      activity were associated with extreme, prolonged acidification of the luminal
      space. These pathological changes in pH led to disruption of intercellular
      junctional coupling, measured by movement of occludin and E-cadherin.
      CONCLUSIONS: By measuring changes in extracellular pH in pancreas of mice, we
      observed that luminal acidification resulted from exocytosis of zymogen granules
      from acinar cells. This process is part of normal organ function but could
      contribute to the tissue damage in cases of acute pancreatitis.

PMID- 20691183
TI  - Collaboration and competition between DNA double-strand break repair pathways.
AB  - DNA double-strand breaks resulting from normal cellular processes including
      replication and exogenous sources such as ionizing radiation pose a serious risk
      to genome stability, and cells have evolved different mechanisms for their
      efficient repair. The two major pathways involved in the repair of double-strand
      breaks in eukaryotic cells are non-homologous end joining and homologous
      recombination. Numerous factors affect the decision to repair a double-strand
      break via these pathways, and accumulating evidence suggests these major repair
      pathways both cooperate and compete with each other at double-strand break sites
      to facilitate efficient repair and promote genomic integrity.

PMID- 20691185
TI  - Should I stay or should I go? Hormonal control of nest abandonment in a long
      lived bird, the Adelie penguin.
AB  - According to life-history theory, long-lived birds should favor their survival
      over the current reproductive attempt, when breeding becomes too costly. In
      seabirds, incubation is often associated with spontaneous long-term fasting.
      Below a threshold in body reserves, hormonal and metabolic shift characteristics
      of a switch from lipid to protein utilization (phase III, PIII) occur. These
      metabolic changes are paralleled by nest abandonment and stimulation of refeeding
      behavior. Parental behavior is then under control of two hormones with opposite
      effects: corticosterone (CORT) and prolactin which stimulate foraging and
      incubation behavior, respectively. The aim of this study was to determine the
      respective role of these two hormones in nest abandonment by Adelie penguins. To
      this end, plasma hormone levels were measured before egg-laying and at departure
      from the colony (i.e. when birds were relieved by their partner or abandoned
      their nest), and related to nutritional state and incubation success. We found
      that males abandoning their nest in PIII presented high CORT levels and low
      prolactin levels. Interestingly, males which presented high plasma levels of
      prolactin in PIII did not abandon. We show that although CORT is the first
      hormone to be affected by prolonged energy constraints, the combined effects of
      high CORT and low prolactin levels are necessary for parents to favor self
      maintenance and abandon the nest. We provide insights into time-course changes of
      the endocrine profile as PIII proceeds and report that reaching proteolytic late
      fasting is not sufficient to induce nest abandonment in a long-lived bird.

PMID- 20691186
TI  - Hosts use altered macronutrient intake to circumvent parasite-induced reduction
      in fecundity.
AB  - Explanations for the evolution of pathogen-induced fecundity reduction usually
      rely on a common principle: the trade-off between host longevity and
      reproduction. Recent advances in nutritional research have, however, challenged
      this assumption and shown that longevity and reproduction are not inextricably
      linked. In this study, we showed that beetles infected by cysticercoids of the
      tapeworm Hymenolepis diminuta increased their total food intake and, more
      particularly, their carbohydrate consumption compared with uninfected insects.
      This increased intake was only pronounced during the first 12 days p.i., when the
      parasite grows and develops into a mature metacestode. Despite consuming more
      nutrients, infected individuals sustained lower levels of body lipid and were
      less efficient at converting ingested protein to body protein. However they
      demonstrated a capacity to compose a diet that sustained high levels of
      reproductive output unless confined to foods that were nutritionally dilute. We
      did not find any indication that macronutrient intakes had an effect on host pro
      phenoloxidase activity; however, phenoloxidase activity was significantly
      affected by protein intake. Our results showed that when offered nutritionally
      complementary diets, infected hosts do not systematically suffer a reduction in
      fecundity. Thus, in our view, the assumption that a reduction in host
      reproduction represents an adaptive response by the host or the parasite to
      divert resources away from reproduction toward other traits should be reassessed.

PMID- 20691187
TI  - Molecular diversity of the microsporidium Kneallhazia solenopsae reveals an
      expanded host range among fire ants in North America.
AB  - Kneallhazia solenopsae is a pathogenic microsporidium that infects the fire ants
      Solenopsis invicta and Solenopsis richteri in South America and the USA. In this
      study, we analyzed the prevalence and molecular diversity of K. solenopsae in
      fire ants from North and South America. We report the first empirical evidence of
      K. solenopsae infections in the tropical fire ant, Solenopsis geminata, and S.
      geminata*Solenopsis xyloni hybrids, revealing an expanded host range for this
      microsporidium. We also analyzed the molecular diversity at the 16S ribosomal RNA
      gene in K. solenopsae from the ant hosts S.invicta, S. richteri, S. geminata and
      S. geminata*S. xyloni hybrids from North America, Argentina and Brazil. We found
      22 16S haplotypes. One of these haplotypes (WD_1) appears to be widely
      distributed, and is found in S. invicta from the USA and S. geminata from
      southern Mexico. Phylogenetic analyses of 16S sequences revealed that K.
      solenopsae haplotypes fall into one of two major clades that are differentiated
      by 2-3%. In some cases, multiple K. solenopsae haplotypes per colony were found,
      suggesting either an incomplete homogenization among gene copies within the 16S
      gene cluster or multiple K. solenopsae variants simultaneously infecting host
      colonies.

PMID- 20691188
TI  - Isolation and identification of Perkinsus olseni from feces and marine sediment
      using immunological and molecular techniques.
AB  - Molecular and immunological probes were used to identify various life stages of
      Perkinsus olseni, a protozoan parasite of the Manila clam Ruditapes
      philippinarum, from a marine environment and decomposing clam tissue. Western
      blotting revealed that the antigenic determinants of the rabbit anti-P. olseni
      antibody developed in this study were peptides with molecular masses of 55.9,
      24.0, and 19.2kDa. Immunofluorescent assay indicated that the rabbit anti-P.
      olseni IgG was specific to all life stages, including the prezoosporangium,
      trophozoite, and zoospore. Perkinsus olseni prezoosporangium-like cells were
      successfully isolated from marine sediment collected from Hwangdo on the west
      coast of Korea, where P. olseni-associated clam mortality has recurred for the
      past decade. Purified cells were positively stained with the rabbit anti-P.
      olseni antibody in an immunofluorescence assay, confirming for the first time the
      presence of P. olseni in marine sediment. Actively replicating zoospores inside
      the prezoosporangia were observed in the decomposing clam tissue collected from
      Hwangdo. P. olseni was also isolated from the feces and pseudofeces of infected
      clams and confirmed by PCR. The clams released 1-2 prezoosporangia per day
      through feces. The data suggested that the fecal discharge and decomposition of
      the infected clam tissue could be the two major P. olseni transmission routes.

PMID- 20691190
TI  - Structural basis for the dual recognition of IL-12 and IL-23 by ustekinumab.
AB  - Interleukin (IL)-12 and IL-23 are heterodimeric proinflammatory cytokines that
      share a common p40 subunit, paired with p35 and p19 subunits, respectively. They
      represent an attractive class of therapeutic targets for the treatment of
      psoriasis and other immune-mediated diseases. Ustekinumab is a fully human
      monoclonal antibody (mAb) that binds specifically to IL-12/IL-23p40 and
      neutralizes human IL-12 and IL-23 bioactivity. The crystal structure of
      ustekinumab Fab (antigen binding fragment of mAb), in complex with human IL-12,
      has been determined by X-ray crystallography at 3.0 A resolution. Ustekinumab Fab
      binds the D1 domain of the p40 subunit in a 1:1 ratio in the crystal, consistent
      with a 2 cytokines:1 mAb stoichiometry, as measured by isothermal titration
      calorimetry. The structure indicates that ustekinumab binds to the same epitope
      on p40 in both IL-12 and IL-23 with identical interactions. Mutational analyses
      confirm that several residues identified in the IL-12/IL-23p40 epitope provide
      important molecular binding interactions with ustekinumab. The electrostatic
      complementarity between the mAb antigen binding site and the p40 D1 domain
      epitope appears to play a key role in antibody/antigen recognition specificity.
      Interestingly, this structure also reveals significant structural differences in
      the p35 subunit and p35/p40 interface, compared with the published crystal
      structure of human IL-12, suggesting unusual and potentially functionally
      relevant structural flexibility of p35, as well as p40/p35 recognition.
      Collectively, these data describe unique observations about IL-12p35 and
      ustekinumab interactions with p40 that account for its dual binding and
      neutralization of IL-12 and IL-23.

PMID- 20691189
TI  - Structural insight into the mechanism of c-di-GMP hydrolysis by EAL domain
      phosphodiesterases.
AB  - Cyclic diguanylate (or bis-(3'-5') cyclic dimeric guanosine monophosphate; c-di
      GMP) is a ubiquitous second messenger that regulates diverse cellular functions,
      including motility, biofilm formation, cell cycle progression, and virulence in
      bacteria. In the cell, degradation of c-di-GMP is catalyzed by highly specific
      EAL domain phosphodiesterases whose catalytic mechanism is still unclear. Here,
      we purified 13 EAL domain proteins from various organisms and demonstrated that
      their catalytic activity is associated with the presence of 10 conserved EAL
      domain residues. The crystal structure of the TBD1265 EAL domain was determined
      in free state (1.8 A) and in complex with c-di-GMP (2.35 A), and unveiled the
      role of conserved residues in substrate binding and catalysis. The structure
      revealed the presence of two metal ions directly coordinated by six conserved
      residues, two oxygens of c-di-GMP phosphate, and potential catalytic water
      molecule. Our results support a two-metal-ion catalytic mechanism of c-di-GMP
      hydrolysis by EAL domain phosphodiesterases.

PMID- 20691191
TI  - Refolding and polymerization pathways of neuroserpin.
AB  - Neuroserpin is a member of the serpin superfamily, and its mutants are retained
      within the endoplasmic reticulum of neurons as ordered polymers in association
      with dementia. It has been proposed that neuroserpin polymers are formed by a
      conformational change in the folded protein. However, an alternative model
      whereby polymers are formed during protein folding rather than from the folded
      protein has recently been proposed. We investigated the refolding and
      polymerization pathways of wild-type neuroserpin (WT) and of the pathogenic
      mutants S49P and H338R. Upon refolding, denatured WT immediately formed an
      initial refolding intermediate I(IN) and then underwent further refolding to the
      native form through a late refolding intermediate, I(R). The late-onset mutant
      S49P was also able to refold to the native form through I(IN) and I(R), but the
      final refolding step proceeded at a slower rate and with a lower refolding yield
      as compared with WT. The early-onset mutant H338R formed I(R) through the same
      pathway as S49P, but the protein could not attain the native state and remained
      as I(R). The I(R)s of the mutants had a long lifespan at 4  degrees C and thus
      were purified and characterized. Strikingly, when incubated under physiological
      conditions, I(R) formed ordered polymers with essentially the same properties as
      the polymers formed from the native protein. The results show that the mutants
      have a greater tendency to form polymers during protein folding than to form
      polymers from the folded protein. Our finding provides insights into biochemical
      approaches to treating serpinopathies by targeting a polymerogenic folding
      intermediate.

PMID- 20691192
TI  - Tail-mediated collapse of HMGB1 is dynamic and occurs via differential binding of
      the acidic tail to the A and B domains.
AB  - The architectural DNA-binding protein HMGB1 consists of two tandem HMG-box
      domains joined by a basic linker to a C-terminal acidic tail, which negatively
      regulates HMGB1-DNA interactions by binding intramolecularly to the DNA-binding
      faces of both basic HMG boxes. Here we demonstrate, using NMR chemical-shift
      mapping at different salt concentrations, that the tail has a higher affinity for
      the B box and that A box-tail interactions are preferentially disrupted.
      Previously, we proposed a model in which the boxes are brought together in a
      collapsed, tail-mediated assembly, which is in dynamic equilibrium with a more
      extended form. Small-angle X-ray scattering data are consistent with such a
      dynamic equilibrium between collapsed and extended structures and are best
      represented by an ensemble. The ensembles contain a significantly higher
      proportion of collapsed structures when the tail is present. (15)N NMR relaxation
      measurements show that full-length HMGB1 has a significantly lower rate of
      rotational diffusion than the tail-less protein, consistent with the loss of
      independent domain motions in an assembled complex. Mapping studies using the
      paramagnetic spin label MTSL [(1-oxyl-2,2,5,5-tetramethyl-3-pyrrolidin-3
      yl)methyl methanethiosulfonate] placed at three locations in the tail confirm our
      previous findings that the tail binds to both boxes with some degree of
      specificity. The end of the tail lies further from the body of the protein and is
      therefore potentially free to interact with other proteins. MTSL labelling at a
      single site in the A domain (C44) causes detectable relaxation enhancements of B
      domain residues, suggesting the existence of a "sandwich"-like collapsed
      structure in which the tail enables the close approach of the basic domains.
      These intramolecular interactions are presumably important for the dynamic
      association of HMGB1 with chromatin and provide a mechanism by which protein
      protein interactions or posttranslational modifications might regulate the
      function of the protein at particular sites, or at particular stages in the cell
      cycle.

PMID- 20691193
TI  - Classification studies based on a spectral representation of DNA.
AB  - The aim of this paper is to provide a new tool to classify the nucleic acid
      sequences. The profiles based on the values characterizing DNA sequences
      (descriptors derived from recently introduced graphical representation) are used
      as a basis of classification schemes related to different aspects of similarity
      of the sequences. New multicomponent similarity measures based on these
      descriptors have been defined. Each component of the new measures can be analyzed
      separately. The new measures are consistent with the standard ones but they
      contain more detailed information. In particular, it has been shown that within
      the new approach one can define a quantity which converges to the standard
      similarity measure. An application of the multicomponent similarity measure to
      families of histone sequences demonstrates the power and efficiency of the
      method.

PMID- 20691194
TI  - Invasions with density-dependent ecological parameters.
AB  - The speed and the minimum carrying capacity needed for a successful population
      expansion into new territory are addressed using a reaction-diffusion model. The
      model is able to encapsulate a rich collection of ecological behaviours,
      including the Allee effect, resource depletion due to consumption, dispersal
      adaptation due to population pressure, biological control agents, and a range of
      breeding suppression mechanisms such as embryonic diapause, delayed development
      and sperm storage. It is shown how many of these phenomena can be characterised
      as density-dependence in a few fundamental ecological parameters. With the help
      of a powerful mathematical technique recently developed by Balasuriya and
      Gottwald (J. Math. Biol. 61, pp. 377-399, 2010), explicit formulae for the effect
      on the speed and minimum carrying capacity are obtained.

PMID- 20691195
TI  - Glial growth factor 2 promotes functional recovery with treatment initiated up to
      7 days after permanent focal ischemic stroke.
AB  - Neuregulins are a family of growth factors essential for normal cardiac and
      nervous system development. The EGF-like domain of neuregulins contains the
      active site which binds and activates signaling cascades through ErbB receptors.
      A neuregulin-1 gene EGF-like fragment demonstrated neuroprotection in the
      transient middle cerebral artery occlusion (MCAO) stroke model and drastically
      reduced infarct volume (Xu et al., 2004). Here we use a permanent MCAO rat model
      to initially compare two products of the neuregulin-1 gene and also assess levels
      of recovery with acute versus delayed time to treatment. In the initial study
      full-length glial growth factor 2 (GGF2) and an EGF-like domain fragment were
      compared with acute intravenous delivery. In a second study GGF2 only was
      delivered starting at 24h, 3 days or 7 days after permanent ischemia was induced.
      In both studies daily intravenous administration continued for 10 days. Recovery
      of neurological function was assessed using limb placing and body swing tests.
      GGF2 had similar functional improvements compared to the EGF-like domain fragment
      at equimolar doses, and a higher dose of GGF2 demonstrated more robust functional
      improvements compared to a lower dose. GGF2 improved sensorimotor recovery with
      all treatment paradigms, even enhancing recovery of function with a delay of 7
      days to treatment. Histological assessments did not show any associated reduction
      in infarct volume at either 48 h or 21 days post-ischemic event. Neurorestorative
      effects of this kind are of great potential clinical importance, given the
      difficulty of delivering neuroprotective therapies within a short time after an
      ischemic event in human patients. If confirmed by additional work including
      additional data on mechanism(s) of improved outcome with verification in other
      stroke models, one can make a compelling case to bring GGF2 to clinical trials as
      a neurorestorative approach to improving outcome following stroke injury.

PMID- 20691196
TI  - Celecoxib induces tolerance in a model of peripheral inflammatory pain in rats.
AB  - Celecoxib is a non-steroidal anti-inflammatory drug (NSAID) that selectively
      inhibits cyclooxygenase-2 (COX-2). Like most NSAIDs, celecoxib exhibits analgesic
      effects in models of inflammatory pain but these appear to be dependent on
      endogenous opioid release. Therefore, this study has assessed the ability of
      celecoxib to induce tolerance in rats, comparable to that induced by morphine.
      Rats were injected subcutaneously (s.c.) twice daily with divided doses of
      celecoxib, morphine or indomethacin. Inflammation was induced in one hind paw of
      rats by injecting prostaglandin E(2) (PGE(2); 200 ng) 30 min after drug
      administration, on days 1, 3, 5 and 6 or 7. Nociceptive thresholds to mechanical
      stimulation were measured 3 h after PGE(2) injection, on the same days. On days 6
      or 7, analgesic effects of the full doses of test drugs were assessed. Celecoxib
      induced tolerance, as did morphine, an effect not shown by another NSAID,
      indomethacin. Cross-tolerance between celecoxib and morphine was observed as they
      did not induce analgesia when animals were chronically treated with morphine or
      celecoxib, respectively. In addition, tolerance to celecoxib's analgesic effects
      persisted for at least two days after the end of the chronic treatment with
      celecoxib. Naltrexone prevented induction of tolerance to morphine or celecoxib.
      The present results strengthen the possibility that celecoxib has also mechanisms
      of analgesia unrelated to COX inhibition but dependent on endogenous opioid
      release. Our results also imply the existence of a new class of analgesics
      without the deleterious effects of COX inhibitors.

PMID- 20691198
TI  - Resonance of cortico-cortical connections of the motor system with the
      observation of goal directed grasping movements.
AB  - Goal directed movements require the activation of parietal, premotor and primary
      motor areas. In monkeys, neurons of these areas become active also during the
      observation of movements performed by others, especially for coding the goal of
      the action (mirror system). Using bifocal transcranial magnetic stimulation (TMS)
      in healthy subjects, we tested whether the observation of goal directed reach to
      grasp actions may lead to specific changes in the short-latency connections
      linking key areas of the mirror system, such as the anterior intraparietal cortex
      (AIP) and the ventral premotor cortex (PMv), with the primary motor cortex (M1).
      We found that AIP-M1 and PMv-M1 cortico-cortical interactions were specifically
      activated when observing successful reaching to grasp goal directed actions, in
      which the hand posture was congruent with the goal of the action performed by the
      actor. On the other hand they were not modified when the same goal directed
      actions were performed wrongly with an inappropriate grasping posture. A similar
      profile of excitability was observed when testing specific intracortical
      facilitatory circuits in M1 (I(2)-waves), known to reflect the activity in
      cortico-cortical pathways transmitting information from PMv. We conclude that the
      simple observation of others' goal directed actions is able to induce specific
      neurophysiological changes in some cortico-cortical circuits of the human motor
      system.

PMID- 20691199
TI  - Frequency responses of age-structured populations: Pacific salmon as an example.
AB  - Increasing evidence of the effects of changing climate on physical ocean
      conditions and long-term changes in fish populations adds to the need to
      understand the effects of stochastic forcing on marine populations. Cohort
      resonance is of particular interest because it involves selective sensitivity to
      specific time scales of environmental variability, including that of mean age of
      reproduction, and, more importantly, very low frequencies (i.e., trends). We
      present an age-structured model for two Pacific salmon species with environmental
      variability in survival rate and in individual growth rate, hence spawning age
      distribution. We use computed frequency response curves and analysis of the
      linearized dynamics to obtain two main results. First, the frequency response of
      the population is affected by the life history stage at which variability affects
      the population; varying growth rate tends to excite periodic resonance in age
      structure, while varying survival tends to excite low frequency fluctuation with
      more effect on total population size. Second, decreasing adult survival
      strengthens the cohort resonance effect at all frequencies, a finding that
      addresses the question of how fishing and climate change will interact.

PMID- 20691197
TI  - The role of ventral medial prefrontal cortex in social decisions: converging
      evidence from fMRI and frontotemporal lobar degeneration.
AB  - The ventral medial prefrontal cortex (vmPFC) has been implicated in social and
      affectively influenced decision-making. Disease in this region may have clinical
      consequences for social judgments in patients with frontotemporal lobar
      degeneration (FTLD). To test this hypothesis, regional cortical activation was
      monitored with fMRI while healthy adults judged the acceptability of brief social
      scenarios such as cutting into a movie ticket line or going through a red light
      at 2 AM. The scenarios described: (i) a socially neutral condition, (ii) a
      variant of each scenario containing a negatively valenced feature, and (iii) a
      variant containing a positively valenced feature. Results revealed that healthy
      adults activated vmPFC during judgments of negatively valenced scenarios relative
      to positive scenarios and neutral scenarios. In a comparative behavioral study,
      the same social decision-making paradigm was administered to patients with a
      social disorder due to FTLD. Patients differed significantly from healthy
      controls, specifically showing less sensitivity to negatively valenced features.
      Comparative anatomical analysis revealed considerable overlap of vmPFC activation
      in healthy adults and vmPFC cortical atrophy in FTLD patients. These converging
      results support the role of vmPFC in social decision-making where potentially
      negative consequences must be considered.

PMID- 20691200
TI  - Ellagic acid protects endothelial cells from oxidized low-density lipoprotein
      induced apoptosis by modulating the PI3K/Akt/eNOS pathway.
AB  - Endothelial apoptosis is a driving force in atherosclerosis development. Oxidized
      low-density lipoprotein (oxLDL) promotes inflammatory and thrombotic processes
      and is highly atherogenic, as it stimulates macrophage cholesterol accumulation
      and foam cell formation. Previous studies have shown that the
      phosphatidylinositol 3-kinase/Akt/endothelial nitric oxide synthase/nitric oxide
      (PI3K/Akt/eNOS/NO) pathway is involved in oxLDL-induced endothelial apoptosis.
      Ellagic acid, a natural polyphenol found in berries and nuts, has in recent years
      been the subject of intense research within the fields of cancer and
      inflammation. However, its protective effects against oxLDL-induced injury in
      vascular endothelial cells have not been clarified. In the present study, we
      investigated the anti-apoptotic effect of ellagic acid in human umbilical vein
      endothelial cells (HUVECs) exposed to oxLDL and explored the possible mechanisms.
      Our results showed that pretreatment with ellagic acid (5-20MUM) significantly
      attenuated oxLDL-induced cytotoxicity, apoptotic features, and generation of
      reactive oxygen species (ROS). In addition, the anti-apoptotic effect of ellagic
      acid was partially inhibited by a PI3K inhibitor (wortmannin) and a specific eNOS
      inhibitor (cavtratin) but not by an ERK inhibitor (PD98059). In exploring the
      underlying mechanisms of ellagic acid action, we found that oxLDL decreased Akt
      and eNOS phosphorylation, which in turn activated NF-kappaB and downstream pro
      apoptotic signaling events including calcium accumulation, destabilization of
      mitochondrial permeability, and disruption of the balance between pro- and anti
      apoptotic Bcl-2 proteins. Those alterations induced by oxLDL, however, were
      attenuated by pretreatment with ellagic acid. The inhibition of oxLDL-induced
      endothelial apoptosis by ellagic acid is due at least in part to its anti-oxidant
      activity and its ability to modulate the PI3K/Akt/eNOS signaling pathway.

PMID- 20691202
TI  - Transforming vision into action.
AB  - Traditionally, research on vision focused on its role in perception and our
      cognitive life. Except for the study of eye movements, which have been regarded
      as an information-seeking adjunct to visual perception, little attention was paid
      to the way in which vision is used to control our actions, particularly the
      movements of our hands and limbs. Over the last 25 years all of that has changed.
      Researchers are now actively investigating the way in which vision is used to
      control a broad range of complex goal-directed action - and are exploring the
      neural substrates of that control. A new model of the functional organization of
      the visual pathways in the primate cerebral cortex has emerged, one that posits a
      division of labor between vision-for-action (the dorsal stream) and vision-for
      perception (the ventral stream). In this review, I examine some of the seminal
      work on the role of vision in the control of manual prehension and on the visual
      cues that play a critical role in this important human skill. I then review the
      key evidence for the perception-action model, particularly with reference to the
      role of the dorsal stream in the control of manual prehension, touching on recent
      work that both reinforces and challenges this account of the organization of the
      visual system.

PMID- 20691201
TI  - Melanopsin-expressing retinal ganglion cells: implications for human diseases.
AB  - In the last decade, there was the seminal discovery of melanopsin-expressing
      retinal ganglion cells (mRGCs) as a new class of photoreceptors that subserve the
      photoentrainment of circadian rhythms and other non-image forming functions of
      the eye. Since then, there has been a growing research interest on these cells,
      mainly focused on animal models. Only recently, a few studies have started to
      address the relevance of the mRGC system in humans and related diseases. We
      recently discovered that mRGCs resist neurodegeneration in two inherited
      mitochondrial disorders that cause blindness, i.e. Leber hereditary optic
      neuropathy and dominant optic atrophy. The mechanism leading to mRGCs sparing in
      these blinding disorders, characterized by extensive and selective loss of RGCs,
      is currently unknown and under investigation. Other studies reported on mRGCs in
      glaucoma, on genetic variation of the melanopsin gene (OPN4) in seasonal
      affective disorder and on the role of mRGCs in migraineous photophobia. Our own
      data and studies from others have shown a significant reduction of mRGCs with
      aging. We anticipate that these studies will lead to many other investigations
      addressing the role of mRGCs and circadian photoreception in the pathogenesis of
      circadian and sleep abnormalities in neurodegenerative disorders.

PMID- 20691203
TI  - System identification in Priming of Pop-Out.
AB  - Inter-trial repetitions of a target's features in a visual search task reduce the
      time needed to find the target. Here I examine these sequential dependencies in
      the Priming of Pop-Out task (PoP) by means of system identification techniques.
      The results are as follows. Response time facilitation due to repetition of the
      target's features increases linearly with difficulty in segmenting the target
      from the distracters. However, z-scoring the reaction times normalizes responses
      by equating facilitation across levels of difficulty. Memory kernels,
      representing the influence of the current trial on any future trial, can then be
      calculated from data normalized and averaged across conditions and observers. The
      average target-defining feature kernel and the target position kernel are well
      fit by a sum of two exponentials model, comprised of a high-gain, fast-decay
      component and a low-gain, slow-decay component. In contrast, the average response
      defining feature kernel is well fit by a single exponential model with very low
      gain and decay similar to the slow component of the target-defining feature
      kernel. Analysis of single participant's data reveals that a fast-decay component
      is often also present for the response-defining feature, but can be either
      facilitatory or inhibitory and thus tends to cancel out in pooled data. Overall,
      the results are similar to integration functions of reward history recently
      observed in primates during frequency-matching experiments. I speculate that
      sequential dependencies in PoP result from learning mechanisms that bias the
      attentional weighting of certain aspects of the stimulus in an effort to minimize
      a prediction error signal.

PMID- 20691204
TI  - Compression of time during smooth pursuit eye movements.
AB  - Humans have a clear sense for the passage of time, but while implicit motor
      timing is quite accurate, explicit timing is prone to distortions particularly
      during action (Wenke & Haggard, 2009) and saccadic eye movements (Morrone, Ross,
      & Burr, 2005). Here, we investigated whether perceived duration is also affected
      by the execution of smooth pursuit eye movements, showing a compression of
      apparent duration similar to that observed during saccades. To this end, we
      presented two brief bars that marked intervals between 100 and 300 ms and asked
      subjects to judge their duration during fixation and pursuit. We found a
      compression of perceived duration for bars modulated in luminance contrast of
      about 32% and for bars modulated in chromatic contrast of 14% during pursuit
      compared to fixation. Interestingly, Weber ratios were similar for fixation and
      pursuit, if they are expressed as ratio between JND and perceived duration. This
      compression was constant for pursuit speeds from 7 to 14 deg/s and did not occur
      for intervals marked by auditory events. These results argue for a modality
      specific component in the processing of temporal information.

PMID- 20691205
TI  - Voltage- and temperature-dependent gating of heterologously expressed
      channelrhodopsin-2.
AB  - Channelrhodopsins are light-activated channels originally isolated from algae
      that are being used increasingly as tools to non-invasively stimulate neurones.
      Despite their widespread use some aspects of their biophysical properties have
      not been fully characterised. Here we report detailed investigation of the gating
      kinetics and voltage-dependence of ChR2 transiently expressed in HEK-293 cells.
      Currents were elicited using light pulses of defined duration and intensity
      generated by a blue LED. Datasets were gathered both at room temperature (RT, ~22
      degrees C) and 37 degrees C. Current responses to light rose rapidly to a peak
      and then desensitized to a steady state plateau. When illumination was terminated
      currents rapidly deactivated. Recovery from desensitization at -85 mV was slow
      with half-times of 1.4 and 3.1s at 37 degrees C and ~22 degrees C, respectively.
      At both temperatures, the reversal potential of ChR2 responses was a few mV
      positive to 0 mV. Both the peak and plateau phases of ChR2 responses exhibited
      strong inward rectification with only small outward currents at positive membrane
      potentials. The rates of ChR2 activation, deactivation and desensitization were
      ~2 times faster at 37 degrees C than at ~22 degrees C. Both the activation and
      deactivation kinetics of ChR2 were significantly slowed by depolarization at both
      temperatures. Additionally, the degree of steady state desensitization was
      greater at more depolarized potentials. The macroscopic desensitization kinetics
      were not voltage-dependent, but recovery from desensitization was slowed by
      depolarization. These gating behaviour data provide an important basis for more
      detailed analysis of the properties and limitations of ChR2 use in more complex
      systems.

PMID- 20691206
TI  - In vitro inhibition of CSFV replication by retroviral vector-mediated RNA
      interference.
AB  - Classical swine fever (CSF) is a highly contagious viral disease of pigs which
      causes major economic losses worldwide. No specific drug is currently available
      for the effective treatment of CSFV infection. RNA interference (RNAi) technology
      depends on effective delivery systems, for which several effective vectors have
      recently been developed. Three retroviral plasmids containing siRNA genes
      targeting different regions of N(pro) and NS4A have been constructed, and 3
      replication-incompetent retroviral vectors have been produced in the human embryo
      kidney cell line GP2-293 by retroviral plasmid transfection. PK-15 cells were
      then infected with these replication-incompetent retroviral vectors and screened
      for siRNA stably expressing PK-15 cell clones. Growth of CSFV in such siRNA
      stably expressing cell clones resulted in a 186-fold reduction in viral genome
      copies and, at 72 h post-infection, only a small % of cells showed infection by
      indirect immunofluorescence microscopy, and effective inhibition of virus
      replication persisted for up to 120 h. Retroviral vector-mediated RNAi can
      therefore be used to study the specific function of viral genes associated with
      CSFV replication and may have potential therapeutic application.

PMID- 20691207
TI  - Mass spectrometry of murine leukemia virus core proteins.
AB  - A mass spectrometry (MS) approach was used to analyze viral core proteins of the
      murine leukemia virus (MuLV)-based gene delivery vector. The retroviral particles
      produced by traditional methods were concentrated and purified by
      ultracentrifugation and spin column for matrix-assisted laser desorption
      ionization (MALDI) and electrospray ionization (ESI) MS. MALDI application
      detected all core MuLV proteins, partial degradation of p10, phosphorylation of
      p12, as well as the previously unknown formation of a polymeric supramolecular
      complex between p15 and p30 core proteins. ESI provided information on the post
      translational modifications of MuLV core proteins. Data suggest myristoylation of
      p15 and oxidation of methionine residues in both p12 and p30, whereas cysteine
      residues in p10, p15 and p30 were not oxidized. The current study demonstrates
      that MALDI and ESI are efficient tools for viral core protein analysis and can be
      used as analytical tools in virology and biotechnology of gene delivery vectors.

PMID- 20691208
TI  - Detection of wheat dwarf virus (WDV) in wheat and vector leafhopper (Psammotettix
      alienus Dahlb.) by real-time PCR.
AB  - Wheat dwarf virus (WDV) is a newly emerging pathogen affecting wheat production
      in China. A real-time PCR method using the TaqMan probe is described for
      quantitative detection of WDV in wheat tissues and in leafhopper (Psammotettix
      alienus Dahlb.). Primers and probes for specific detection of WDV were designed
      within the conserved region of the coat protein (CP) gene sequence. A sensitivity
      assay showed the detection limit of the assay was 30 copies, and the standard
      curve was linear over range 30-3 * 10(6) copies, with good reproducibility.
      Simultaneously, this real-time PCR assay could be used to detect WDV CP genes in
      viruliferous leafhoppers. As determined by an end-point dilution comparison, real
      time PCR was close to 10(4)-fold more sensitive than the indirect enzyme-linked
      immunosorbent assay for WDV detection. Field samples of wheat and leafhopper
      collected from different regions of China were detected by both real-time PCR and
      gel-based PCR. The results showed more positive samples could be identified by
      real-time PCR than by gel-based PCR. This quantitative detection assay provides a
      valuable tool for diagnosis and molecular studies of WDV biology.

PMID- 20691209
TI  - A novel RT-multiplex PCR for detection of Aichi virus, human parechovirus,
      enteroviruses, and human bocavirus among infants and children with acute
      gastroenteritis.
AB  - A novel reverse transcription-multiplex polymerase chain reaction assay was
      developed to detect Aichi virus, human parechovirus, enteroviruses, and human
      bocavirus. A mixture of four pairs of published specific primers, 6261 and 6779,
      ev22(+) and ev22(-), F1 and R1, 188F and 542R, was used to amplify the viral
      genomes and specifically generate four different amplicon sizes of 519, 270, 440,
      and 354 bp for Aichi virus, human parechovirus, enteroviruses, and human
      bocavirus, respectively. A total of 247 fecal specimens previously screened for
      rotavirus, adenovirus, norovirus, sapovirus, and astrovirus-negative, collected
      from infants and children with acute gastroenteritis in Japan from July 2007 to
      June 2008, were tested further for the presence of the four viruses, Aichi virus,
      human parechovirus, enteroviruses, and human bocavirus, by RT-multiplex PCR. The
      total detection rate of these viruses was 26.7% (66 out of 247 samples). Of
      these, HPeV, EVs, and HBoV were identified in 20, 41, and 5 specimens. No Aichi
      virus was found among these subjects. The sensitivity and specificity of RT
      multiplex PCR were assessed and demonstrated a strong validation against RT
      monoplex PCR. This is the first report of detecting these types of viruses in
      fecal samples from infants and children with acute gastroenteritis by RT
      multiplex PCR.

PMID- 20691210
TI  - The impact of PCR-generated recombination on diversity estimation of mixed viral
      populations by deep sequencing.
AB  - Ultra-deep pyrosequencing (UDPS) of targeted amplicons allows to determine a
      large number of individual sequence reads from a single PCR product, and this
      approach is thus extremely valuable for analysis of mixed viral populations. A
      mixture of genetically distinct DNA templates, however, may lead to the
      generation of recombinant sequences during the initial PCR amplification step. In
      the present study, the frequency at which these misleading PCR artefacts are
      formed has been estimated by using artificial mixtures of genetically distinct
      human cytomegalovirus (HCMV) DNA templates for a given cycling profile. The
      presence of similar copy numbers of non-identical HCMV target sequences, combined
      with high levels of input HCMV DNA, as is found in some clinical samples, favored
      the formation of recombinant PCR products. Thus, to estimate the full natural
      diversity within mixed viral populations using UDPS, artificial chimeras
      generated during the PCR step should be taken into account as a potential
      artefact.

PMID- 20691211
TI  - Rapid antiviral assay using QD-tagged fish virus as imaging nanoprobe.
AB  - Development of rapid antiviral assays can expedite the process of screening
      potential agents against viral pathogens. In the present study, fluorescent
      quantum dots (QDs) incorporated with infectious pancreatic necrosis virus (IPNV)
      were used as imaging nanoprobes to detect the threshold amount of poly I:C (an
      interferon inducer) required to induce zebrafish cells into an antiviral state
      against IPNV. QD-IPNV hybrids were formed by colloidal clustering of negatively
      charged QDs and IPNV, using the cationic polymer polybrene (50 MUg/mL). To test
      the screening potential of the QD-IPNV hybrids for anti-IPNV drug candidates,
      zebrafish ZF4 cells primed with the immunostimulant poly I:C at concentrations of
      1, 5, and 10 MUg/mL for 6h were used as a model system. After poly I:C treatment,
      cells were exposed to the QD-IPNV hybrids for 6h at a multiplicity of infection
      (MOI) of 5. The anti-IPNV effectiveness of poly I:C was assessed via fluorescence
      intensity of the QDs. Our results showed that ZF4 cells primed with poly I:C at
      10 MUg/mL were highly protected from IPNV challenge (i.e., no detection of QD
      fluorescence). In summary, a rapid and efficient cell-based imaging platform has
      been developed for assessing the anti-IPNV activity of poly I:C on ZF4 cells
      using QD-IPNV hybrids. This approach may be applied to a wider range of fish
      species and fish pathogenic viruses.

PMID- 20691212
TI  - Repertoire of antibodies against type 1 poliovirus in human sera.
AB  - A blocking-ELISA procedure was used to quantify antibodies in sera of humans
      immunized with poliovirus vaccines. Titers determined by this method demonstrated
      an excellent correlation with the results of neutralization test. Testing of
      serum potency with a panel of type 1 poliovirus strains altered antigenically was
      used to evaluate the composition of polyclonal sera with respect to the epitope
      specificity of constituent antibodies. Paratope profiles of various polyclonal
      sera determined by this new method differed, depending on the type of vaccine
      used for immunization. Antibodies induced in response to inactivated poliovirus
      vaccine (IPV) contained antibodies directed primarily against antigenic site 1,
      while sera from recipients of the oral poliovirus vaccine (OPV) contained
      antibodies to site 3. Antibodies to antigenic sites 2 and 4 were minor
      constituents in both types of sera. Pre-immunization sera had paratope profiles
      similar to OPV-induced antisera, allowing the discrimination between antibodies
      induced by IPV and maternal antibodies. The new method may be useful for
      analyzing results of clinical trials and to compare immunity induced by different
      poliovirus vaccines.

PMID- 20691213
TI  - The effect of purification method on the completeness of the immature HIV-1 Gag
      shell.
AB  - Elucidating the structure of the immature HIV-1 Gag core is an important aspect
      of understanding the biology of this virus. In doing so, preservation of the
      fragile Gag lattice is essential. In this study, the effects of purification
      methods on the structural and mechanical integrity of immature HIV-1 are
      examined. The results show that the morphological and mechanical properties of
      the virion are preserved to a significantly higher degree by Iodixanol (OptiPrep)
      purification compared to the standard sucrose method. In conclusion, these
      results indicate that OptiPrep instead of sucrose purification should be employed
      when conducting structural studies on the HIV-1 virion.

PMID- 20691214
TI  - Loop-mediated isothermal amplification for rapid detection and differentiation of
      wild-type pseudorabies and gene-deleted virus vaccines.
AB  - A loop-mediated isothermal amplification (LAMP) assay was developed specifically
      for detection and differentiation of pseudorabies virus (PRV). One group of
      primers was designed to detect wild-type strains (i.e., strains with the gE gene)
      and the other group of primers was designed to detect both PRV gE-vaccine and
      wild-type strains (i.e., strains with the gG gene and with or without the gE
      gene). After amplification by Bst enzyme at a constant temperature of 65 degrees
      C, a laddering of bright products was visible following electrophoresis on a 2%
      agarose gel. LAMP was 100-1000-fold more sensitive than the standard PCR. The
      assay was specific in that it did not amplify other porcine viruses including
      porcine parvovirus, porcine circovirus type 1, porcine circovirus type 2, porcine
      reproductive and respiratory syndrome virus, classical swine fever virus, swine
      transmissible gastroenteritis coronavirus, and porcine epidemic diarrhea virus.
      Because of its sensitivity, specificity, and simplicity, the LAMP assay could be
      a useful method for early and rapid differentiation of swine vaccinated with PRV
      gE-deleted vaccine from swine infected with wild virus.

PMID- 20691215
TI  - Transmission studies with Cassava brown streak Uganda virus (Potyviridae:
      Ipomovirus) and its interaction with abiotic and biotic factors in Nicotiana
      benthamiana.
AB  - Cassava brown streak disease (CBSD), caused by two distinct species, Cassava
      brown streak Uganda virus (CBSUV) and Cassava brown streak virus (CBSV), is a
      major constraint to cassava (Manihot esculenta Crantz) production in Africa.
      Absence of infectious clones of CBSUV or CBSV and the lack of efficient means of
      mechanical transmission of CBSD has hampered laboratory studies of this disease.
      Mechanical transmission, achieved mainly by plant sap inoculation, is a widely
      used technique for characterizing plant viruses. Efficient sap transmission of
      CBSUV/CBSV to the common laboratory host Nicotiana benthamiana is essential for
      both basic and applied studies of the virus. We report here the development of an
      efficient protocol for sap transmission of CBSUV to N. benthamiana and N.
      debneyi. Several factors affecting transmission efficiency were identified such
      as the effects of buffer composition, antioxidants, inoculum concentration, plant
      age and temperature. Higher temperatures (30  degrees C) favored rapid symptom
      initiation compared to lower temperatures (21  degrees C) when sap prepared in
      phosphate buffer of pH 7.0 was applied on the leaves of N. benthamiana dusted
      with the abrasive (carborundum). We demonstrated the usefulness of the
      transmission method in transient evaluation of CBSUV[UG:Nam:04]-derived RNA
      interference constructs for CBSD resistance and also in studying the interaction
      of CBSUV[UG:Nam:04] with cassava mosaic geminiviruses, another important group of
      viruses infecting cassava.

PMID- 20691216
TI  - An economical single-sided antibody incubation method for Western blotting.
AB  - A simple, single-sided antibody method for incubating primary and secondary
      antibodies in Western blotting was developed, which generates significant savings
      on the use of antibodies. Compared with the conventional immersion technique for
      antibody incubation, the present economical single-sided antibody incubation
      method resulted in a saving of 80% of antibody use. Besides, the present
      incubation method did not compromise the Western blot results and was not
      affected by the expression levels of target proteins.

PMID- 20691217
TI  - Increase of core temperature induced by corticotropin-releasing factor and
      urocortin: a comparative study.
AB  - This study compared the ability of CRF and UCN1 to induce a thermoregulatory
      response when centrally injected into rats. The effects of antipyretic drugs and
      CRF receptor antagonists (CRF1 and CRF2) on the temperature (T) changes induced
      by these peptides were also investigated. Rectal (rT) and tail skin (T(sk))
      temperatures were measured with a thermistor probe while body (bT) temperature
      was measured with a battery-operated biotelemetry transmitter in male Wistar rats
      (200 g) every 30 min over a period of 6h, after intracerebroventricular (i.c.v.)
      injection of 1 nmol of either CRF or UCN1. Rats were pre-treated with
      indomethacin (2 mg kg-1, i.p.) or celecoxib (5 mg kg-1, p.o.), dexamethasone (0.5
      mg kg-1, s.c.), astressin (a CRF1/CRF2 antagonist, 7 nmol, i.c.v.) or antalarmin
      (a CRF1 antagonist, 20 mg kg-1, i.p.). The increase in body temperature induced
      by CRF was accompanied by a reduction in T(sk) while the response induced by UCN1
      was accompanied by an elevation in T(sk). Indomethacin or celecoxib did not
      change the increases in rT caused by either CRF or UCN1. Although dexamethasone
      attenuated the increase in rectal temperature in response to CRF, dexamethasone
      did not modify the response induced by UCN1. Astressin blocked the UCN1-induced
      hyperthermia and reduced CRF-induced fever. Antalarmin did not modify the
      hyperthermia in response to UCN1, but reduced the fever evoked by CRF. This study
      demonstrated that CRF by acting on the CRF1 receptor induces a prostaglandin
      independent fever which seems to depend, at least in part, on the synthesis of
      other mediators while UCN1 acts on the CRF2 receptor, promoting a hyperthermic
      response which seems to be independent on synthesis/release of any mediator.

PMID- 20691218
TI  - Greater expression of inflammatory cytokines, adrenomedullin, and natriuretic
      peptide receptor-C in epicardial adipose tissue in coronary artery disease.
AB  - BACKGROUND: Growing evidence suggests that the epicardial adipose tissue may have
      local interactions with coronary arteries. In addition, vasoactive peptides such
      as adrenomedullin and natriuretic peptide has an interaction with adipose tissue.
      In this study, we investigated the relationship between adipokines,
      adipocytokines, and vasoactive peptides expressed in epicardial adipose tissue
      and subcutaneous adipose tissue in patients with and without coronary artery
      disease (CAD). METHODS: We studied 20 patients with CAD and 14 patients without
      CAD. We obtained blood samples and epicardial and subcutaneous adipose tissue at
      open-heart surgery. We measured serum cytokine levels and used real-time
      polymerase chain reaction (PCR) to measure mRNA levels of various molecules in
      epicardial and subcutaneous tissue and investigated the relation between mRNA
      levels and clinical parameters. RESULTS: The mRNA levels of IL-6, IL-1beta, MCP
      1, and TNF-alpha were significantly higher in epicardial adipose tissue than in
      subcutaneous adipose tissue. Interestingly, the mRNA levels of IL-6, IL-1beta,
      MCP-1, natriuretic peptide receptor-C (NPR-C), adrenomedullin, and leptin in
      epicardial adipose tissue were higher in patients with CAD than those without
      CAD. In contrast, mRNA levels of adiponectin, PPAR-gamma, and NPR-A were similar
      in the two groups. In subcutaneous tissue, mRNA expressions of IL-6, IL-1beta,
      MCP-1, NPR-C, adrenomedullin, and leptin were modestly higher in patients with
      CAD than in those without CAD. There were no differences in plasma cytokine
      levels between the two groups. CONCLUSION: The mRNA levels of inflammatory
      cytokines, adipokines, neurohumoral factors and their receptors appear to be
      increased in epicardial adipose tissue independent of plasma levels of these
      molecules. Further studies are necessary to elucidate the pathophysiological role
      of these molecules in CAD.

PMID- 20691219
TI  - Thymosin beta4 induces the expression of vascular endothelial growth factor
      (VEGF) in a hypoxia-inducible factor (HIF)-1alpha-dependent manner.
AB  - Thymosin beta4 has multi-functional roles in cell physiology, but little is known
      about its mechanism(s) of action. We previously reported that thymosin beta4
      stimulated angiogenesis through the induction of vascular endothelial growth
      factor (VEGF). To identify the mechanism of VEGF induction by thymosin beta4, we
      have used a luciferase assay system with VEGF in the 5' promoter region. We also
      analyzed the effect of thymosin beta4 on VEGF mRNA stability and on the
      expression and stability of hypoxia-inducible factor (HIF)-1alpha. We found that
      thymosin beta4 induces VEGF expression by an increase in the stability of HIF
      1alpha protein. Analysis of the expression patterns of thymosin beta4 and HIF
      1alpha in colon cancer tissue microarray showed that thymosin beta4 and HIF
      1alpha co-localized in these biopsies. These data show that thymosin beta4
      induces the expression of VEGF indirectly by increasing the protein stability of
      HIF-1alpha.

PMID- 20691220
TI  - Primary effect of 1alpha,25(OH)2D3 on IL-10 expression in monocytes is short-term
      down-regulation.
AB  - The biologically most active vitamin D compound, 1alpha,25-dihydroxyvitamin D3
      (1alpha,25(OH)2D3), influences the status of inflammation by modulating the
      expression of several cytokine genes. In this study, we have examined the
      mechanism of transcriptional regulation of interleukin 10 (IL-10) by
      1alpha,25(OH)2D3 in lipopolysaccharide (LPS)-treated human monocytes (THP-1).
      Quantitative PCR showed that IL-10 mRNA expression was significantly down
      regulated (2.8-fold) during the first 8h of 1alpha,25(OH)2D3 treatment, while
      after 48 h it was up-regulated (3-fold). Gel shift and quantitative chromatin
      immunoprecipitation (ChIP) assays showed that the vitamin D receptor (VDR) binds
      in a cyclical fashion to a promoter region 1500-1700 bp upstream of the IL-10
      transcription start site (TSS) containing two conserved VDR binding sites.
      Targeting of VDR binding sites by enhancer specific duplex RNAs revealed that
      only the more distal element is functional and chromosome conformation capture
      analysis suggested that this region loops 1alpha,25(OH)2D3-dependently to the
      TSS. Quantitative ChIP and micrococcal nuclease assays also revealed
      1alpha,25(OH)2D3-dependent cyclical epigenetic changes and nucleosome remodeling
      at this promoter region. In conclusion, in LPS-treated THP-1 cells the primary
      effect of 1alpha,25(OH)2D3 on IL-10 expression is down-regulation, which is
      achieved via a cyclical recruitment of VDR to the promoter.

PMID- 20691221
TI  - A method of purification, identification and characterization of beta-glucosidase
      from Trichoderma koningii AS3.2774.
AB  - In this study, we used native gradient-polyacrylamide gel electrophoresis and
      electroelution (NGGEE) to purify enzymatic proteins from Trichoderma koningii
      AS3.2774. With this method, we purified eight enzymatic proteins and classified
      them to the cellulase system by comparing secretions of T. koningii in inductive
      medium and in repressive medium. It resulted in 24-fold beta-glucosidase (BG)
      purification with a recovery rate of 5.5%, and a specific activity of 994.6IUmg(
      1) protein. The final yield of BG reached 8MUg under purifying procedure of
      NGGEE. We also identified BG using the enzyme assay with thin-layer
      chromatography and MALDI-TOFMS. This BG had one subunit with a molecular mass of
      69.1kDa as determined by sodium dodecylsulfate-polyacrylamide gel
      electrophoresis. The hydrolytic activity of the BG had an optimal pH of 5.0, an
      optimal temperature of 50 degrees C, an isoelectric point of 5.68 and a K(m) for
      p-nitrophenyl-beta-d-glucopyranoside of 2.67mM. Taken together, we show that
      NGGEE is a reliable method through which MUg grade of active proteins can be
      purified.

PMID- 20691222
TI  - A simplified erythromycin resistance cassette for Treponema denticola
      mutagenesis.
AB  - The primary selectable marker for the genetic studies of Treponema denticola is a
      hybrid gene cassette containing both ermF and ermAM (ermB) genes. ErmB functions
      in Escherichia coli, while ErmF has been assumed to confer resistance in T.
      denticola. We demonstrate here that ErmB is sufficient for erythromycin selection
      in T. denticola and that the native ermB promoter drives ErmB expression.

PMID- 20691223
TI  - Effects of sieving, drying and rewetting upon soil bacterial community structure
      and respiration rates.
AB  - Soil microcosm studies often require some form of soil homogenisation, such as
      sieving, to provide a representative sample. Frequently, soils are also
      homogenised following drying and are then rewetted, yet little research has been
      done to understand how these methods impact upon microbial communities. Here we
      compared the molecular diversity and functional responses of intact cores from a
      Scottish grassland soil with homogenised samples prepared by drying, sieving and
      rewetting or freshly sieving wet soils. Results showed that there was no
      significant difference in total soil CO(2)-C efflux between the freshly sieved
      and intact core treatments, however, respiration was significantly higher in the
      dried and rewetted microcosms. Molecular fingerprinting (T-RFLP) of bacterial
      communities at two different time-points showed that both homogenisation methods
      significantly altered bacterial community structure with the largest differences
      being observed after drying and rewetting. Assessments of responsive taxa in each
      treatment showed that intact cores were dominated by Acidobacterial peaks whereas
      an increased relative abundance of Alphaproteobacterial terminal restriction
      fragments were apparent in both homogenised treatments. However, the shift in
      community structure was not as large in the freshly sieved soil. Our findings
      suggest that if soil homogenisation must be performed, then fresh sieving of wet
      soil is preferable to drying and rewetting in approximating the bacterial
      diversity and functioning of intact cores.

PMID- 20691224
TI  - Microalgae as substrates for fermentative biogas production in a combined
      biorefinery concept.
AB  - Most organic matter can be used for bioenergy generation via anaerobic
      fermentation. Today, crop plants like maize play the dominant role as substrates
      for renewable biogas production. In this work we investigated the suitability of
      six dominant microalgae species (freshwater and saltwater algae and
      cyanobacteria) as alternative substrates for biogas production. We could
      demonstrate that the biogas potential is strongly dependent on the species and on
      the pretreatment. Fermentation of the green alga Chlamydomonas reinhardtii was
      efficient with a production of 587 ml(+/-8.8 SE) biogas g volatile solids(-1)
      (VS(-1)), whereas fermentation of Scenedesmus obliquus was inefficient with only
      287 ml(+/-10.1 SE) biogas g VS(-1) being produced. Drying as a pretreatment
      decreased the amount of biogas production to ca. 80%. The methane content of
      biogas from microalgae was 7-13% higher compared to biogas from maize silage. To
      evaluate integrative biorefinery concepts, hydrogen production in C. reinhardtii
      prior to anaerobic fermentation of the algae biomass was measured and resulted in
      an increase of biogas generation to 123% (+/-3.7 SE). We conclude that selected
      algae species can be good substrates for biogas production and that anaerobic
      fermentation can seriously be considered as final step in future microalgae-based
      biorefinery concepts.

PMID- 20691225
TI  - Increasing the thermostability of sucrose phosphorylase by multipoint covalent
      immobilization.
AB  - Sucrose phosphorylase from Bifidobacterium adolescentis was recombinantly
      expressed in Escherichia coli and purified by use of a His-tag. Kinetic
      characterization of the enzyme revealed an optimal temperature for phosphorolytic
      activity of 58 degrees C, which is surprisingly high for an enzyme from a
      mesophilic source. The temperature optimum could be further increased to 65
      degrees C by multipoint covalent immobilization on Sepabeads EC-HFA. The optimal
      immobilization conditions were determined by surface response design. The highest
      immobilization yield (72%) was achieved in a phosphate buffer of 0.04 mM at pH
      7.2, irrespective of the temperature. The immobilized enzyme was able to retain
      65% of its activity after 16 h incubation at 60 degrees C. Furthermore,
      immobilization of the enzyme in the presence of its substrate sucrose, increased
      this value to 75%. The obtained biocatalyst should, therefore, be useful for
      application in carbohydrate conversions at high temperatures, as required by the
      industry.

PMID- 20691226
TI  - Reconstruction of lymph vessel by lymphatic endothelial cells combined with
      polyglycolic acid scaffolds: a pilot study.
AB  - Restoration of lymphatic drainage using lymph vessels or tissue grafting is
      becoming an efficient method for alleviating obstructive lymphedema. However, the
      lack of ideal lymphatic grafts is the key problem that limits the application of
      lymphatic transplantation, but now that may be resolved with tissue-engineered
      lymph vessels. In this study, the feasibility of reconstructing lymph vessels was
      explored using lymphatic endothelial cells (LECs) combined with polyglycolic acid
      (PGA) scaffolds. The highly purified human dermal LECs can be isolated from human
      dermis by immunomagnetic bead sorting and multiplied in culture. The viability
      and growth potential of subcultured LECs make it possible to obtain large amount
      of cells in vitro. Light and scanning electron microscopy (SEM) showed that the
      prefabricated PGA scaffolds, with three-dimensional structure, can support cell
      adhesion, growth and spreading. The constructs formed with LECs combined with PGA
      scaffolds were cultured in vitro for 10 days and then implanted subcutaneously
      into nude mice. Six weeks after implantation, the portions of implanted tubules
      were harvested. Gross and histological observation demonstrated that the tubular
      structure still remained in the experimental groups but not in the control
      groups. Immunohistochemical staining and RT-PCR assay of the implanted vessels
      revealed positive staining in experimental groups for the lymphatic specific
      markers Podoplanin, VEGFR-3 and LYVE-1. The results indicate that LECs can serve
      as seed cells and be successfully combined with PGA scaffolds, and the tissue
      engineered tubular structure using implanted LECs-PGA compounds showed
      preliminary characteristics of lymph vessels. A gap between the nearly normal or
      functional lymph vessel still exists as we have only the endothelial cell-lined
      duct, but this study demonstrates that it is feasible to construct tissue
      engineered lymph vessels using LECs combined with a biodegradable material.

PMID- 20691227
TI  - Ultrasound-triggered release of materials entrapped in microbubble-liposome
      constructs: a tool for targeted drug delivery.
AB  - We investigated the preparation of ultrasound-triggered drug delivery system,
      based on a pendant complex of microbubble coated with liposomes. Biotinylated
      decafluorobutane microbubbles were coated with biotinylated liposomes via a
      streptavidin linker. Liposomes were prepared incorporating calcein and thrombin.
      Based on initial concentration of calcein, over 1 um(3) payload volume per each
      microbubble-liposome particle was achieved, when 100 nm liposomes were used.
      Insonation of microbubble-liposome pendants in vitro resulted in the complete
      destruction of microbubbles and triggered release of a significant fraction of
      the entrapped material. Treatment with 1MHz ultrasound (5 pulses, 100 ms, 7 MPa
      peak negative acoustic pressure) resulted in the release of ~30% of entrapped
      calcein, as estimated by the fluorescence quenching assay. Thrombin release from
      liposomes complexed with microbubbles (11% of entrapped material) due to
      ultrasound treatment was estimated by a chromogenic substrate study. Prior to
      insonation, substrate hydrolysis was at background level. Ultrasound-triggered
      release of thrombin from the pendant complexes caused an acceleration of blood
      clotting.

PMID- 20691228
TI  - Extended release of dexamethasone from silicone-hydrogel contact lenses
      containing vitamin E.
AB  - Ophthalmic drug delivery by contact lenses is expected to be more efficient due
      to continuous extended release of drug and increased residence time in the tear
      film. However, commercial contact lenses release ophthalmic drugs for a short
      period of about an hour and are thus not suitable for extended delivery use. Here
      we explore a novel approach of increasing the release duration of dexamethasone
      (DX) from commercial contact lenses by loading Vitamin E into the lenses. The
      Vitamin E was loaded into the lenses by soaking the lenses in Vitamin E-ethanol
      solution followed by ethanol removal through evaporation. The results show that
      with about 30% of Vitamin E loading in the contact lens, the DX release time can
      be increased to 7 to 9 days for ACUVUE((r)) OASYSTM, NIGHT&DAYTM, and
      O(2)OPTIXTM, which is a 9 to 16 fold increase compared to the DX release duration
      by pure contact lens without Vitamin E loading. The DX delivery by contact lens
      can be viewed as a one-dimensional transport by a flat thin film, and a
      mathematical model based on the drug diffusivity difference between Vitamin E and
      silicone hydrogel was also proposed to explain the DX release time increase by
      Vitamin E loaded contact lens.

PMID- 20691231
TI  - Getting a bigger slice of the pie. Effects on eating and emotion in restrained
      and unrestrained eaters.
AB  - Manipulated perceptions of the portion size of food influence subsequent eating
      by restrained and unrestrained eaters. In the present study, all participants
      were served a same-sized slice of pizza. For one-third of participants, their
      slice appeared larger than the slice being served to another ostensible
      participant, another third perceived their slice as smaller, and the final third
      did not see a second slice. All participants then proceeded to "taste and rate"
      cookies in an ad lib eating opportunity. A significant interaction reflected the
      fact that when the pizza slice was perceived as large, restrained eaters tended
      to eat more cookies whereas unrestrained eaters tended to eat less cookies.
      Emotion data suggest that the differential responses of restrained and
      unrestrained eaters to the belief that they have overeaten relative to another
      eater influenced their subsequent dissimilar ad lib eating behavior.

PMID- 20691229
TI  - Nanoparticle-based theranostic agents.
AB  - Theranostic nanomedicine is emerging as a promising therapeutic paradigm. It
      takes advantage of the high capacity of nanoplatforms to ferry cargo and loads
      onto them both imaging and therapeutic functions. The resulting nanosystems,
      capable of diagnosis, drug delivery and monitoring of therapeutic response, are
      expected to play a significant role in the dawning era of personalized medicine,
      and much research effort has been devoted toward that goal. A convenience in
      constructing such function-integrated agents is that many nanoplatforms are
      already, themselves, imaging agents. Their well-developed surface chemistry makes
      it easy to load them with pharmaceutics and promote them to be theranostic
      nanosystems. Iron oxide nanoparticles, quantum dots, carbon nanotubes, gold
      nanoparticles and silica nanoparticles, have been previously well investigated in
      the imaging setting and are candidate nanoplatforms for building up nanoparticle
      based theranostics. In the current article, we will outline the progress along
      this line, organized by the category of the core materials. We will focus on
      construction strategies and will discuss the challenges and opportunities
      associated with this emerging technology.

PMID- 20691230
TI  - Overcoming drug resistance by regulating nuclear receptors.
AB  - Drug resistance involves multiple mechanisms. Multidrug resistance (MDR) is the
      leading cause of treatment failure in cancer therapy. Elevated levels of MDR
      proteins [members of the ATP-binding cassette (ABC) transporter family] increase
      cellular efflux and decrease the effectiveness of chemotherapeutic agents. As a
      salvage approach to overcome drug resistance, inhibitors of MDR proteins have
      been developed, but have had limited success mainly due to undesired toxicities.
      Nuclear receptors (NRs), including pregnane X receptor (PXR), regulate the
      expression of proteins (including MDR proteins) involved in drug metabolism and
      drug clearance, suggesting that it is possible to overcome drug resistance by
      regulating NR. This review discusses the progress in the development of MDR
      inhibitors, with a focus on MDR1 inhibitors. Recent development of PXR
      antagonists to pharmacologically modulate PXR is also reviewed. The review
      proposes that selectively preventing the elevation of MDR levels by regulating
      NRs rather than non-selectively inhibiting the MDR activity by using MDR
      inhibitors can be a less toxic approach to overcome drug resistance during cancer
      therapy.

PMID- 20691233
TI  - Ghrelin and obestatin promote the allergic action in rat peritoneal mast cells as
      basic secretagogues.
AB  - Ghrelin is an endogenous ligand of the type 1a growth hormone secretagogue
      receptor (GHSR1a) that regulates energy balance. Ghrelin and obestatin, derived
      from the post-translational processing of preproghrelin, are involved in a
      diverse range of biological activities, yet their effect on the immune system is
      not fully understood. In the present study, we investigated the roles of ghrelin
      and obestatin on mast cell degranulation and found that both ghrelin and
      obestatin induce the release of histamine from rat peritoneal mast cells. This
      induced histamine release was inhibited by the pertussis toxin, an inhibitor of
      Galpha(i) protein, and extracellular Ca(2+). Rat peritoneal mast cells and rat
      basophilic leukemia (RBL-2H3) cells did not express the ghrelin receptor GHSR1a,
      suggesting that histamine release induced by ghrelin occurs via a receptor
      independent mechanism. We report here that ghrelin and obestatin, belonging to
      the family of basic secretagogues, stimulate mast cells independent of a
      receptor, and this may play a crucial role at the site of allergy or
      inflammation.

PMID- 20691232
TI  - A new subfamily of conotoxins belonging to the A-superfamily.
AB  - Two novel conotoxins from vermivorous cone snails Conus pulicarius and Conus
      tessulatus, designated as Pu14.1 and ts14a, were identified by cDNA cloning and
      peptide purification, respectively. The signal sequence of Pu14.1 is identical to
      that of alpha-conotoxins, while its predicted mature peptide, pu14a, shares high
      sequence similarity with ts14a, with only one residue different in their first
      intercysteine loop, which contains 10 residues and is rich in proline. Both pu14a
      and ts14a contain four separate cysteines in framework 14 (C-C-C-C). Peptide
      pu14a was chemically synthesized, air oxidized, and the connectivity of its two
      disulfide bonds was determined to be C1-C3, C2-C4, which is the same as found in
      alpha-conotoxins. The synthetic pu14a induced a sleeping symptom in mice and was
      toxic to freshwater goldfish upon intramuscular injection. Using the Xenopus
      oocyte heterologous expression system, 1MUM of pu14a demonstrated to inhibit the
      rat neuronal alpha3beta2-containing as well as the mouse neuromuscular
      alpha1beta1gammadelta subtypes of nicotinic acetylcholine receptors, and then
      rapidly dissociated from the receptors. However, this toxin had no inhibitory
      effect on potassium channels in mouse superior cervical ganglion neurons.
      According to the identical signal sequence to alpha-conotoxins, the unique
      cysteine framework and molecular target of pu14a, we propose that pu14a and ts14a
      may represent a novel subfamily in the A-superfamily, designated as alpha1
      conotoxins.

PMID- 20691234
TI  - Molecular dynamics simulations of Abeta fibril interactions with beta-sheet
      breaker peptides.
AB  - Accumulation and aggregation of the 42-residue amyloid-beta (Abeta) protein
      fragment, which originates from the cleavage of amyloid precursor protein by beta
      and gamma secretase, correlates with the pathology of Alzheimer's disease (AD).
      Possible therapies for AD include peptides based on the Abeta sequence, and
      recently identified small molecular weight compounds designed to mimic these,
      that interfere with the aggregation of Abeta and prevent its toxic effects on
      neuronal cells in culture. Here, we use molecular dynamics simulations to compare
      the mode of interaction of an active (LPFFD) and inactive (LHFFD) beta-sheet
      breaker peptide with an Abeta fibril structure from solid-state NMR studies. We
      found that LHFFD had a weaker interaction with the fibril than the active
      peptide, LPFFD, from geometric and energetic considerations, as estimated by the
      MM/PBSA approach. Cluster analysis and computational alanine scanning identified
      important ligand-fibril contacts, including a possible difference in the effect
      of histidine on ligand-fibril pi-stacking interactions, and the role of the
      proline residue in establishing contacts that compete with those essential for
      maintenance of the inter-monomer beta-sheet structure of the fibril. Our results
      show that molecular dynamics simulations can be a useful way to classify the
      stability of docking sites. These mechanistic insights into the ability of LPFFD
      to reverse aggregation of toxic Abeta will guide the redesign of lead compounds,
      and aid in developing realistic therapies for AD and other diseases of protein
      aggregation.

PMID- 20691235
TI  - 2-Phenylethylamine, a constituent of chocolate and wine, causes mitochondrial
      complex-I inhibition, generation of hydroxyl radicals and depletion of striatal
      biogenic amines leading to psycho-motor dysfunctions in Balb/c mice.
AB  - Behavioral and neurochemical effects of chronic administration of high doses of 2
      phenylethylamine (PEA; 25-75 mg/kg, i.p. for up to 7 days) have been investigated
      in Balb/c mice. Depression and anxiety, as demonstrated respectively by increased
      floating time in forced swim test, and reduction in number of entries and the
      time spent in the open arms in an elevated plus maze were observed in these
      animals. General motor disabilities in terms of akinesia, catalepsy and decreased
      swimming ability were also observed in these animals. Acute and sub-acute
      administration of PEA caused significant, dose-dependent depletion of striatal
      dopamine, and its metabolites levels. PEA caused dose-dependent generation of
      hydroxyl radicals in vitro in Fenton's reaction in test tubes, in isolated
      mitochondrial fraction, and in vivo in the striatum of mice. A significant
      inhibition of NADH-ubiquinone oxidoreductase (complex-I; EC: 1.6.5.3) activity
      suggests the inhibition in oxidative phosphorylation in the mitochondria
      resulting in hydroxyl radical generation. Nissl staining and TH
      immnunohistochemistry in brain sections failed to show any morphological
      aberrations in dopaminergic neurons or nerve terminals. Long-term over
      consumption of PEA containing food items could be a neurological risk factor
      having significant pathological relevance to disease conditions such as
      depression or motor dysfunction. However, per-oral administration of higher doses
      of PEA (75-125 mg/kg; 7 days) failed to cause such overt neurochemical effects in
      rats, which suggested safe consumption of food items rich in this trace amine by
      normal population.

PMID- 20691236
TI  - Protective effects of indomethacin-loaded nanocapsules against oxygen-glucose
      deprivation in organotypic hippocampal slice cultures: involvement of
      neuroinflammation.
AB  - Targeted treatment of diseases of the central nervous system remains problematic
      due to the complex pathogenesis of these disorders and the difficulty in drug
      delivery. Here we investigate the neuroprotective effect of indomethacin-loaded
      nanocapsules (IndOH-NC) in an in vitro model of ischemia. For this purpose we
      used organotypic hippocampal cultures exposed to oxygen-glucose deprivation
      (OGD). When the cultures were exposed to 60 min of OGD, 54.5+/-14.7% of the total
      area of the hippocampal slices was labeled with propidium iodide. On the other
      hand, when the cultures were treated with 50 or 100 MUM of IndOH-NC the cell
      death was significantly reduced to 31+/-7% (P<0.05) and 20+/-4% (P<0.001),
      respectively. The treatment with IndOH-NC markedly inhibited the levels of the
      pro-inflammatory cytokines IL-1beta, IL-6 and TNF-alpha levels even 48 h after
      OGD. Immunoblotting revealed that treatment with 100 MUM of IndOH-NC was able to
      significantly reduce to the levels of control cultures the levels of ERK1/2 and
      JNK phosphorylation, as well as iNOS activation. Additionally, IndOH-NC prevented
      glial activation induced by OGD, as evidenced by a decrease of GFAP immunocontent
      and Isolectin B(4) reactivity. Our results clearly demonstrate that IndOH-NC
      might represent a promising pharmaceutical neuroprotective formulation for
      cerebral ischemia, most probably by inhibiting the inflammatory cascades.

PMID- 20691237
TI  - Olanzapine abuse was relieved after switching to aripiprazole in a patient with
      psychotic depression.

PMID- 20691238
TI  - Protective effect of simple phenols from extravirgin olive oil against lipid
      peroxidation in intestinal Caco-2 cells.
AB  - Complex polyphenols present in extravirgin olive oil are not directly absorbed,
      but undergo gastrointestinal biotransformation, increasing the relative amount of
      tyrosol (TYR) and hydroxytyrosol (HT) entering the small and large intestine. We
      investigated the capacity of TYR and HT to inhibit the insult of dietary lipid
      hydroperoxydes on the intestinal mucosa, using cultures of Caco-2, a cell line
      with enterocyte-like features, and studying the effect of tert-butyl
      hydroperoxide (TBH) treatment on specific cell membrane lipid targets. The effect
      of homovanillic alcohol (HVA), metabolite of HT in humans and detected as
      metabolite of HT in Caco-2 cells, was also evaluated. Exposure to TBH induced a
      significant increase of the level of MDA, the formation of fatty acid
      hydroperoxides and 7-ketocholesterol and the loss of alpha-tocopherol.
      Pretreatment with both HT and HVA protected Caco-2 cells from oxidative damage:
      there was no significant detection of oxidation products and the level of alpha
      tocopherol was preserved. Noteworthy, TYR also exerted a protective action
      against fatty acids degradation. In vitro trials, where the simple phenols were
      tested during linoleic acid and cholesterol oxidation, gave evidence of a direct
      scavenging of peroxyl radicals and suggested a hydrogen atom-donating activity.

PMID- 20691239
TI  - The absence of genotoxicity of sucralose.
AB  - Sucralose is a non-nutritive sweetener that is approximately 600 times sweeter
      than table sugar. It is currently approved for use in over 80 countries. Evidence
      from chronic studies demonstrates that this compound is not carcinogenic. This
      report summarizes the results of genotoxicity studies that were part of the
      original safety assessment of sucralose-conducted early in the safety
      investigation and shared with regulatory agencies around the world. Studies
      included the Ames (Salmonella typhimurium) reverse mutation test, the Escherichia
      coli pol A+/A- test, an in vitro chromosome damage assay in human lymphocytes,
      mutation in TK +/- mouse lymphoma cells, an in vivo chromosome aberration test in
      rats and two separate micronucleus tests in mice. All results were evaluated as
      negative. These results support the overall conclusion by regulatory and heath
      agencies that sucralose is safe for its intended use.

PMID- 20691240
TI  - The dietary flavonoid apigenin blocks phorbol 12-myristate 13-acetate-induced COX
      2 transcriptional activity in breast cell lines.
AB  - Cyclooxygenase (COX)-2 is the inducible isozyme catalyzing the conversion of
      arachidonic acid to prostanoids. Its expression has been linked to the process of
      carcinogenesis, including tumorigenesis of the breast. Apigenin (APG) is a
      flavone commonly found in fruit and vegetables, and is shown to be a potential
      modulator in inflammatory diseases. This study examined the potential suppressive
      effect of the flavone on phorbol ester-induced COX-2 expression in the breast
      cell lines MCF-10A and MCF-7. Real-time PCR and/or Western blotting indicated
      that APG in micromolar range significantly inhibited phorbol 12-myristate 13
      acetate (PMA)-induced COX-2 expression in these breast cells. APG treatment
      reduced the amount of phospho-mitogen-activated protein kinase (MAPK) ERK-1/2,
      but it did not alter the activity of PKC. Activated ERKs might trigger the
      transactivation of AP-1 or CRE, which can be located at COX-2 promoter region (
      72/-53). Reporter gene assay as well as electrophoretic mobility shift assays
      (EMSA) illustrated that APG inhibited transcription factor binding at this region
      in a dose-dependent manner. This study showed that APG down-regulated PMA-induced
      COX-2 expression in breast cells without affecting PKC activity. These findings
      could provide a scientific basis for developing APG nutraceutical against breast
      carcinogenesis.

PMID- 20691241
TI  - Appearance of konzo in South-Kivu, a wartorn area in the Democratic Republic of
      Congo.
AB  - Konzo is an upper motor neuron disease characterized by sudden-onset and
      irreversible spastic paraparesis occurring in nutritionally compromised people.
      It is associated with consumption of insufficiently processed cyanogenic-toxic
      cassava. Cassava, the main caloric source in the Democratic Republic of Congo,
      has been safely consumed for decades in the Eastern Province of South-Kivu.
      However, in the context of long-lasting war and violent conflicts, cases of
      spastic paraparesis resembling konzo appeared in a populous area (Burhinyi). Two
      field surveys (2003 and 2005) identified 41 subjects meeting clinical criteria of
      konzo and suffering from (chronic) malnutrition. Their urinary thiocyanate
      concentrations (median 129, range 20-688, SD 146 MUg/L), and cyanogen levels
      (median 20 ppm, range 5-300 ppm, SD 73 ppm) in cassava roots from their household
      stocks were high. The source of cyanogenic-toxicity was unprocessed fresh cassava
      roots during harvest period, but probably also insufficiently processed roots.
      This first report of konzo in South-Kivu concludes that occurrence of konzo was
      triggered by food shortages because of the longstanding state of insecurity.
      Contributory factors included the introduction of new varieties of (bitter)
      cassava, but konzo may actually be caused by a combination of factors that are
      yet to be understood.

PMID- 20691242
TI  - Mammary gland differentiation by early life exposure to enantiomers of the soy
      isoflavone metabolite equol.
AB  - The role of soy in reducing breast cancer risk has been suggested to be
      associated with early exposure to isoflavones, which alter mammary gland
      morphology. The objective of the study was to determine the effect of dietary
      exposure to the enantiomers of a key soy isoflavone metabolite, equol, on mammary
      gland development and later chemoprotection using the DMBA-induced animal model
      of breast cancer. Animals were exposed to S-(-)equol or R-(+)equol (250 mg/kg
      diet) during the neonatal (0-21 days) or prepubertal (21-35 days) periods only.
      Histological evaluation of the mammary glands showed that both enantiomers fed
      neonatally via the dam led to significant precocial mammary gland
      differentiation. By day 50, early S-(-)equol or R-(+)equol exposure resulted in a
      decrease in immature terminal end structures and an increase in mature lobules,
      suggesting an early 'imprinting' effect. Despite these morphological changes to
      the mammary gland, neonatal and prepubertal exposure to equol had no long-term
      chemoprevention against mammary tumors induced by DMBA, although for R-(+)equol
      there was a trend to delaying tumor formation. In summary, early exposure to
      equol was not chemopreventive, but neither did it increase tumor formation in
      response to DMBA, suggesting exposure in early life does not influence breast
      cancer risk.

PMID- 20691243
TI  - Sulfur amino acids deficiency caused by grass pea diet plays an important role in
      the toxicity of L-beta-ODAP by increasing the oxidative stress: studies on a
      motor neuron cell line.
AB  - Neurolathyrism is a motor neuron disease caused by the overconsumption of grass
      pea (Lathyrus sativus L.) containing L-beta-ODAP. The precise mechanism to cause
      motor neuron degeneration has yet to be elucidated, but should agree with the
      epidemiological backgrounds. Considering the amino acid content of the legume,
      and the epidemiological link with prolonged unbalanced nutrition, the shortage of
      sulfur amino acids methionine and cysteine could affect the toxicity of L-beta
      ODAP. We analyzed the effect of these amino acids in the media on the toxicity
      using primary motor neuron culture and a motor neuron cell line NSC-34.
      Deprivation of both methionine and cysteine exacerbated the toxicity of L-beta
      ODAP by 66% compared to the complete medium. The glutathione content of these
      cells was greatly decreased in sulfur amino acid-deprived medium. L-beta-ODAP
      further lowered the content in the deprived media to be 32-44% of the controls
      compared to normal media being 62-74%. The increased motor neuron toxicity in
      this medium was neutralized by the addition of reduced glutathione ethyl ester or
      N-acetylcysteine suggesting the importance of the mitochondrial oxidative stress
      induced by L-beta-ODAP under sulfur amino acid-deficient conditions.

PMID- 20691244
TI  - Consuming organic versus conventional vegetables: the effect on nutrient and
      contaminant intakes.
AB  - The health benefits of consuming organic compared to conventional foods are
      unclear. This study aimed at evaluating the nutrient and contaminant intake of
      adults through consumption of organic versus conventional vegetables, namely
      carrots, tomatoes, lettuce, spinach and potatoes. A probabilistic simulation
      approach was used for the intake assessment in two adult populations: (1) a
      representative sample of Belgians (n=3245) and (2) a sample of Flemish organic
      and conventional consumers (n=522). Although significant differences in nutrient
      and contaminant contents were previously found between organic and conventional
      vegetables, they were inconsistent for a component and/or vegetable. These
      findings were translated here into inconsistent intake assessments. This means
      that the intake of specific nutrients and contaminants can be higher or lower for
      organic versus conventional vegetables. However, when considering the consumption
      pattern of organic consumers, an increase in intake of a selected set of
      nutrients and contaminants is observed, which are explained by the general higher
      vegetable consumption of this consumer group. In public health terms, there is
      insufficient evidence to recommend organic over conventional vegetables. The
      general higher vegetable consumption of organic compared to conventional
      consumers outweighs usually the role of differences in nutrient and contaminant
      concentrations between organic and conventional vegetables.

PMID- 20691245
TI  - Anti-inflammatory activity of bark of Dioscorea batatas DECNE through the
      inhibition of iNOS and COX-2 expressions in RAW264.7 cells via NF-kappaB and
      ERK1/2 inactivation.
AB  - We identified a bioactive herbal medicine with anti-inflammatory activity from an
      ethanol extract derived from the bark of Dioscorea batatas DECNE (BDB) in
      RAW264.7 cells. We examined the effects of BDB on nitric oxide (NO) and
      prostaglandin E(2) (PGE(2)) production in LPS-induced RAW264.7 cells. BDB
      consistently inhibited both NO and PGE(2) production in a dose-dependent manner,
      with an IC(50) of 87-71 MUg/ml, respectively. The reduction of NO and PGE(2)
      production were accompanied by a reduction in iNOS and COX-2 protein expression,
      as evaluated by Western blotting. To evaluate the action mode of BDB and its
      ability to inhibit iNOS and COX-2 protein expression, we assessed the effects of
      BDB on nuclear factor-kappaB (NF-kappaB) DNA-binding activity, NF-kappaB
      dependent reporter gene activity, inhibitory factor-kappaB (IkappaB)
      phosphorylation and degradation, and p65 nuclear translocation. BDB suppressed
      DNA-binding activity and reporter gene activity as well as translocation of the
      NF-kappaB p65 subunit. BDB also down-regulated IkappaB kinase (IKK), thus
      inhibiting LPS-induced both phosphorylation and the degradation of IkappaBalpha.
      In addition, BDB also inhibited the LPS-induced activation of ERK1/2.

PMID- 20691246
TI  - Down-regulation of the phosphoenolpyruvate carboxykinase gene in human colon
      tumors and induction by omega-3 fatty acids.
AB  - The polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA) reduces
      proliferation of several cell types, including colon tumor cells, and regulates
      gene expression in a cell- and gene-selective manner. In hepatocytes, the fatty
      acid synthase (FAS) gene is down-regulated by DHA whereas the carnitine
      palmitoyltransferase-1 (CPT-1) gene is up-regulated. In adipocytes but not in
      hepatocytes, the expression of the cytosolic phosphoenolpyruvate carboxykinase
      (PEPCK-C) gene is stimulated by unsaturated FA, including DHA. We monitored the
      expression of the FAS, CPT-1 and PEPCK-C genes in rat and human colon and in
      colonic tumors from humans. The ratio of PEPCK-C to FAS transcripts was in favor
      of PEPCK-C in human and rat colon, whereas the opposite occurred in Caco2 tumoral
      cells. FAS gene expression declined from proliferative to differentiated Caco2
      cells, while in contrast the expression of PEPCK-C and CPT-1 genes increased. DHA
      strongly induced expression of the PEPCK-C and CPT-1 genes, in correlation with
      decreased cell growth, while, as expected, it reduced FAS mRNA. We assessed the
      relative expression of PEPCK-C, CPT-1 and FAS genes in fragments of colonic
      tumors and adjacent non-tumoral tissue from a series of 10 patients. PEPCK-C and
      CPT-1 mRNAs are more abundant in non-tumoral tissues than in the tumoral
      counterpart, whereas the opposite occurred for the FAS gene. Therefore, the PEPCK
      C gene can be defined as a new negative marker for colonic tumors and a target
      for the anti-tumorigenic action of omega-3 PUFAs.

PMID- 20691247
TI  - A genome-wide association study of Cloninger's temperament scales: implications
      for the evolutionary genetics of personality.
AB  - Variation in personality traits is 30-60% attributed to genetic influences.
      Attempts to unravel these genetic influences at the molecular level have, so far,
      been inconclusive. We performed the first genome-wide association study of
      Cloninger's temperament scales in a sample of 5117 individuals, in order to
      identify common genetic variants underlying variation in personality.
      Participants' scores on Harm Avoidance, Novelty Seeking, Reward Dependence, and
      Persistence were tested for association with 1,252,387 genetic markers. We also
      performed gene-based association tests and biological pathway analyses. No
      genetic variants that significantly contribute to personality variation were
      identified, while our sample provides over 90% power to detect variants that
      explain only 1% of the trait variance. This indicates that individual common
      genetic variants of this size or greater do not contribute to personality trait
      variation, which has important implications regarding the genetic architecture of
      personality and the evolutionary mechanisms by which heritable variation is
      maintained.

PMID- 20691248
TI  - Combined effect of tumor necrosis factor (TNF)-alpha and heat shock protein (HSP)
      70 in reducing apoptotic injury in hypoxia: a cell culture study.
AB  - Studies have demonstrated neuroprotective effects of either TNF-alpha or HSP-70
      in ischemia/reperfusion injury following exercise. However, the protective
      mechanisms involving combined effect of the two proteins, particularly in
      neuronal apoptosis, remain unclear. This study aims to elucidate the beneficial
      role of TNF-alpha and HSP-70 in the regulation of apoptotic proteins and ERK
      signaling in hypoxic injury. Cortical neurons from 20 Sprague-Dawley rat embryos
      were isolated and cultured in five groups with or without pretreatment with
      recombinant TNF-alpha, HSP-70 protein or both prior to hypoxic conditions: (1)
      control; (2) control/hypoxia; (3) TNF-alpha/hypoxia; (4) HSP-70/hypoxia and (5)
      TNF-alpha/HSP-70/hypoxia. Western blotting was used to detect pro- and anti
      apoptotic proteins, including Bax, AIF, Bcl-xL, Bcl-2, and pERK1/2 protein. TNF
      alpha and HSP-70 significantly (p<0.05) reduced the levels of pro-apoptotic
      proteins, Bax and AIF. Also, pretreatment of hypoxic brain tissue with TNF-alpha
      and HSP-70 significantly (p<0.05) enhanced the levels of anti-apoptotic protein,
      Bcl-xL. TNF-alpha and HSP-70 together increased Bcl-2 levels by 70%. Hypoxia
      caused a significant (p<0.05) increase in ERK1/2 phosphorylation levels by 224%.
      The most effective inhibition of ERK levels was obtained by the combined
      administration of TNF-alpha and HSP-70. This study suggested that TNF-alpha and
      HSP-70 together enhance the decrease in pro-apoptotic protein levels and the
      increase in anti-apoptotic protein levels in the event of neuronal hypoxia
      through ERK1/2 signal transduction.

PMID- 20691249
TI  - Selective cytotoxicity of intense nanosecond-duration electric pulses in
      mammalian cells.
AB  - BACKGROUND: Nanosecond electric pulses (EP) disrupt cell membrane and organelles
      and cause cell death in a manner different from the conventional irreversible
      electroporation. We explored the cytotoxic effect of 10-ns EP (quantitation,
      mechanisms, efficiency, and specificity) in comparison with 300-ns, 1.8- and 9
      MUs EP. METHODS: Effects in Jurkat and U937 cells were characterized by survival
      assays, DNA electrophoresis and flow cytometry. RESULTS: 10-ns EP caused
      apoptotic or necrotic death within 2-20 h. Survival (S, %) followed the absorbed
      dose (D, J/g) as: S=alphaD((-K)), where coefficients K and alpha determined the
      slope and the "shoulder" of the survival curve. K was similar in all groups,
      whereas alpha was cell type- and pulse duration-dependent. Long pulses caused
      immediate propidium uptake and phosphatidylserine (PS) externalization, whereas
      10-ns pulses caused PS externalization only. CONCLUSIONS: 1.8- and 9-MUs EP cause
      cell death efficiently and indiscriminately (LD50 1-3 J/g in both cell lines); 10
      ns EP are less efficient, but very selective (LD50 50-80 J/g for Jurkat and 400
      500 J/g for U937); 300-ns EP show intermediate effects. Shorter EP open propidium
      impermeable, small membrane pores ("nanopores"), triggering different cell death
      mechanisms. GENERAL SIGNIFICANCE: Nanosecond EP can selectively target certain
      cells in medical applications like tumor ablation.

PMID- 20691250
TI  - Furanocoumarins-imperatorin inhibits myocardial hypertrophy both in vitro and in
      vivo.
AB  - The furanocoumarin imperatorin has been reported to have hypotensive effect, and
      we have investigated its activity on myocardial hypertrophy. Imperatorin
      displayed similar chromatographic retention peak to verapamil in the model of
      cardiac muscle/cell membrane chromatography, and could reduce in a concentration
      dependent way protein content and cell size of myocytes prestimulated with
      angiotensin II. The ratio of heart weight to body weight (mg/g) (4.13 +/- 0.06 in
      SHRs, 3.77 +/- 0.02 with imperatorin 25 mg kg(-1)d(-1) 16 17 ig, P<0.01) was
      significantly lower in the imperatorin-treated SHRs. Taken together, our
      observations show that imperatorin exerts anti-hypertrophic effect both in vitro
      and in vivo.

PMID- 20691251
TI  - Sustained prolonged topical delivery of bioactive human insulin for potential
      treatment of cutaneous wounds.
AB  - Skin damaged by heat, radiation, or chemical exposure is difficult to treat and
      slow to heal. Indeed full restoration of the tissue is difficult to obtain. Sub
      dermal insulin injection was recently shown to stimulate wound healing of the
      skin by accelerating wound closure, stimulating angiogenesis and inducing a
      regenerative process of healing. We have developed a topical delivery vehicle
      that is capable of releasing therapeutic levels of bioactive insulin for several
      weeks with the potential to stimulate and sustain healing. By encapsulating the
      crystalline form of insulin within poly(d,l-lactide-co-glycolide) microspheres,
      we succeeded in stabilizing and then releasing bioactive insulin for up to 25
      days. To measure bioactivity we used Rat L6 myofibroblasts, stimulated them with
      this slow release insulin and determined activation of the receptors on the cell
      surface by quantifying AKT phosphorylation. There was only a minor and gradual
      decrease in AKT phosphorylation over time. To determine whether the slow release
      insulin could stimulate keratinocyte migration, wounding was simulated by
      scratching confluent cultures of human keratinocytes (HaCaT). Coverage of the
      scratch "wounds" was significantly faster in the presence of insulin released
      from microspheres than in the insulin-free control. Extended and sustained
      topical delivery of active insulin from a stable protein crystal-based reservoir
      shows promise in promoting tissue healing.

PMID- 20691253
TI  - Postnatal experiences influence the behavior in adult male and female Fischer and
      Lewis rats.
AB  - The postnatal environment with the rat pups' dam as the most important regulator,
      plays a central role in determining developmental processes of the offspring.
      Early disturbances of the dam-pup-dyade, like separation from the dam for hours
      (maternal deprivation, MD), or a short period of separation, and exposure to
      novelty, like the handling stimulation (HA), might induce long-lasting changes
      within the individual. To further investigate the susceptibility to these
      postnatal manipulations with regard to both, sex and genetic background, we used
      male and female Fischer (F344) and Lewis (LEW) rats. F344 and LEW rats were daily
      subjected to either HA, MD, or were left undisturbed until weaning. The immediate
      effects of these manipulations were studied using the mother-pup-interaction-test
      on postnatal days 3-7. At the age of 4 months, animals were subjected to a
      behavioral test battery, determining activity, exploration, and anxiety-like
      behavioral parameters. Postnatal manipulations induced significant alterations of
      the mother-pup-interaction patterns that were more pronounced in F344 dams. MD
      and HA F344 dams were longer off pups than LEW dams. MD F344 pups were longer
      groomed than MD LEW pups and HA F344 pups were longer passive nursed than HA LEW
      pups. In adulthood, F344 rats showed increased anxiety-like behavior compared to
      LEW rats. Furthermore, females of both strains exhibited more anxiety-like
      behavior than males. Test independently, MD led to more anxiety-like behavior and
      less exploratory responses, while handled rats exhibited an anxiolytic-like
      behavior and increased exploratory responses. In conclusion, postnatal
      experiences specifically altered the behavioral phenotype in adulthood. While
      these changes were co-directional in the two strains and in both sexes, the
      degree of susceptibility varied.

PMID- 20691254
TI  - Identification of tuna species in commercial cans by minor groove binder probe
      real-time polymerase chain reaction analysis of mitochondrial DNA sequences.
AB  - Three different minor groove binder (MGB) probe assays have been developed for
      rapid and accurate identification of the species commonly used for production of
      canned tuna, i.e. yellowfin (Thunnus albacares), bluefin (Thunnus thynnus) and
      albacore (Thunnus alalunga) tunas. The assays targeting the mitochondrial
      cytochrome b gene were able to discriminate efficiently between the three species
      contained in fresh or canned tunas and did not react with other Scombroidei that
      were tested. A correct species prediction was obtained even from artificial
      mixtures prepared with different amounts of the reference tuna species and
      subjected to the sterilisation treatment. Testing of 27 commercial canned tunas
      by PCR-RFLP, MGB probe assays and sequence analysis showed a concordance of 100%
      between the last two techniques, whereas by using PCR-RFLP several samples were
      uncharacterised or mischaracterised. These results make the established MGB probe
      assays an attractive tool for direct and rapid species identification in canned
      tuna.

PMID- 20691255
TI  - Identification and delineation of members of the Entamoeba complex by
      pyrosequencing.
AB  - A method using a single-round PCR coupled to pyrosequencing was developed for the
      detection and differentiation of members of the Entamoeba complex. The technique
      was evaluated using DNA isolated directly from faecal specimens and compared with
      a duplex real-time PCR targeting Entamoeba histolytica and Entamoeba dispar, and
      a conventional single-round PCR for the detection of Entamoeba moshkovskii.
      Tetranucleate cysts from 102 faecal specimens from Swedish, Danish and Dutch
      patients test-positive for the Entamoeba complex by coproscopic examination were
      identified to species using each of the three methods. Although none of the
      patients were confirmed to be positive for E. moshkovskii, E. histolytica and E.
      dispar were identified in 17 and 86 of the samples, respectively, one of the
      samples containing both species. There was concordance in results between
      pyrosequencing and the two other methods used. This study showed that PCR and
      pyrosequencing could be used for the rapid and high throughput identification of
      Entamoeba species.

PMID- 20691252
TI  - White matter neuron alterations in schizophrenia and related disorders.
AB  - Increased density and altered spatial distribution of subcortical white matter
      neurons (WMNs) represents one of the more well replicated cellular alterations
      found in schizophrenia and related disease. In many of the affected cases, the
      underlying genetic risk architecture for these WMN abnormalities remains unknown.
      Increased density of neurons immunoreactive for Microtubule-Associated Protein 2
      (MAP2) and Neuronal Nuclear Antigen (NeuN) have been reported by independent
      studies, though there are negative reports as well; additionally, group
      differences in some of the studies appear to be driven by a small subset of
      cases. Alterations in markers for inhibitory (GABAergic) neurons have also been
      described. For example, downregulation of neuropeptide Y (NPY) and nitric oxide
      synthase (NOS1) in inhibitory WMN positioned at the gray/white matter border, as
      well as altered spatial distribution, have been reported. While increased density
      of WMN has been suggested to reflect disturbance of neurodevelopmental processes,
      including neuronal migration, neurogenesis, and cell death, alternative
      hypotheses--such as an adaptive response to microglial activation in mature CNS,
      as has been described in multiple sclerosis--should also be considered. We argue
      that larger scale studies involving hundreds of postmortem specimens will be
      necessary in order to clearly establish the subset of subjects affected.
      Additionally, these larger cohorts could make it feasible to connect the cellular
      pathology to environmental and genetic factors implicated in schizophrenia,
      bipolar disorder, and autism. These could include the 22q11 deletion
      (Velocardiofacial/DiGeorge) syndrome, which in some cases is associated with
      neuronal ectopias in white matter.

PMID- 20691256
TI  - Generalized progressive retinal atrophy in the Irish Glen of Imaal Terrier is
      associated with a deletion in the ADAM9 gene.
AB  - Generalized progressive retinal atrophy (gPRA) belongs to a group of inherited
      retinal diseases which are associated with gradual vision loss in various dog
      breeds, including the Irish Glen of Imaal Terrier (GIT). By genome-wide
      homozygosity mapping using SNP arrays and fine mapping of candidate regions, we
      assigned the gPRA candidate locus in this breed to canine chromosome 16. The
      respective region is syntenic with human chromosome 8 comprising the ADAM
      metallopeptidase domain 9 (ADAM9) gene. ADAM9 represents a strong candidate gene
      for canine retinal disease because mutations have previously been shown to cause
      autosomal recessively inherited human cone-rod dystrophy, a retinal disorder
      affecting photoreceptor function. Sequence analysis of ADAM9 in affected and
      carrier GITs revealed a deletion of exons 15 and 16 which alters the reading
      frame leading to a premature stop codon. This mutation was absent from 34 other
      dog breeds. A variable and, at times, very late onset of gPRA was confirmed in
      GITs by a relatively mild retinal degeneration at an advanced age. Hence, the
      identification of the genetic defect underlying gPRA in the GIT represents a
      suitable model for cone-rod dystrophy of humans, with superior potential to
      elucidate functional consequences of the recently described null mutations in the
      human ADAM9 gene.

PMID- 20691257
TI  - Arecoline, a major alkaloid of the areca nut, causes neurotoxicity through
      enhancement of oxidative stress and suppression of the antioxidant protective
      system.
AB  - Arecoline, an areca nut alkaloid, has been noted for its potential cognition
      enhancing effects in patients with Alzheimer dementia. However, it has been
      confirmed that areca nut use is associated with oral and pharyngeal cancers. In
      addition, arecoline is genotoxic and cytotoxic both in vitro and in vivo through
      oxidative stress-dependent mechanisms. The aim of this study was to investigate
      whether arecoline would interfere with the antioxidant defense system and induce
      cytotoxicity in rat primary cortical neurons. Results indicate that arecoline (50
      200 MUM) induces neuronal cell death, and catalase, NADPH oxidase inhibitors
      (diphenyleneiodonium chloride and apocynin), and a caspase inhibitor (z-VAD-fmk)
      can prevent arecoline-induced cell death. Furthermore, arecoline increased
      reactive oxygen species production and upregulated protein expression and mRNA
      levels of NADPH oxidase 2, which could be attenuated by catalase and NADPH
      oxidase inhibitors. Arecoline also attenuated neuronal antioxidant defense by
      decreasing glutathione (GSH) level and superoxide dismutase activity. In
      addition, arecoline enhanced the expression of proapoptotic proteins (cytochrome
      c, Bax, caspase-9, and caspase-3) and attenuated the expression of the
      antiapoptotic protein Bcl-2. Moreover, NADPH oxidase inhibitors could attenuate
      the arecoline-induced GSH depletion and reverse arecoline-induced changes in
      proapoptotic and antiapoptotic proteins. In conclusion, the results indicate that
      arecoline could induce neuronal apoptotic death by attenuating antioxidant
      defense and enhancing oxidative stress.

PMID- 20691258
TI  - Ciliates rapidly enhance the frequency of conjugation between Escherichia coli
      strains through bacterial accumulation in vesicles.
AB  - The mechanism underlying bacterial conjugation through protozoa was investigated.
      Kanamycin-resistant Escherichia coli SM10lambda+ carrying pRT733 with TnphoA was
      used as donor bacteria and introduced by conjugation into ciprofloxacin-resistant
      E. coli clinical isolate recipient bacteria. Equal amounts of donor and recipient
      bacteria were mixed together in the presence or absence of protozoa (ciliates,
      free-living amoebae, myxamoebae) in Page's amoeba saline for 24 h.
      Transconjugants were selected with Luria broth agar containing kanamycin and
      ciprofloxacin. The frequency of conjugation was estimated as the number of
      transconjugants for each recipient. Conjugation frequency in the presence of
      ciliates was estimated to be approximately 10-6, but in the absence of ciliates,
      or in the presence of other protozoa, it was approximately 10-8. Conjugation also
      occurred in culture of ciliates at least 2 h after incubation. Successful
      conjugation was confirmed by the polymerase chain reaction. Addition of
      cycloheximide or latrunculin B resulted in suppression of conjugation. Heat
      killing the ciliates or bacteria had no effect on conjugation frequency. Co
      localization of green fluorescent protein-expressing E. coli and PKH-67-vital
      stained E. coli was observed in the same ciliate vesicles, suggesting that both
      donor and recipient bacteria had accumulated in the same vesicle. In this study,
      the conjugation frequency of bacteria was found to be significantly higher in
      vesicles purified from ciliates than those in culture suspension. We conclude
      that ciliates rapidly enhance the conjugation of E. coli strains through
      bacterial accumulation in vesicles.

PMID- 20691259
TI  - Methadone induces necrotic-like cell death in SH-SY5Y cells by an impairment of
      mitochondrial ATP synthesis.
AB  - Methadone is a widely used therapeutic opioid in narcotic addiction and
      neuropathic pain syndromes. Oncologists regularly use methadone as a long-lasting
      analgesic. Recently it has also been proposed as a promising agent in leukemia
      therapy, especially when conventional therapies are not effective. Nevertheless,
      numerous reports indicate a negative impact on human cognition with chronic
      exposure to opiates. Thus, clarification of methadone toxicity is required. In SH
      SY5Y cells we found that high concentrations of methadone were required to induce
      cell death. Methadone-induced cell death seems to be related to necrotic
      processes rather than typical apoptosis. Cell cultures challenged with methadone
      presented alterations in mitochondrial outer membrane permeability. A mechanism
      that involves Bax translocation to the mitochondria was observed, accompanied
      with cytochrome c release. Furthermore, no participation of known protein
      regulators of apoptosis such as Bcl-X(L) and p53 was observed. Interestingly,
      methadone-induced cell death took place by a caspases-independent pathway;
      perhaps due to its ability to induce a drastic depletion in cellular ATP levels.
      Therefore, we studied the effect of methadone on isolated rat liver mitochondria.
      We observed that methadone caused mitochondrial uncoupling, coinciding with the
      ionophoric properties of methadone, but did not cause swelling of the organelles.
      Overall, the effects observed for cells in the presence of supratherapeutic doses
      of methadone may result from a "bioenergetic crisis." A decreased level of
      cellular energy may predispose cells to necrotic-like cell death.

PMID- 20691260
TI  - Untranslated regions of thyroid hormone receptor beta 1 mRNA are impaired in
      human clear cell renal cell carcinoma.
AB  - Thyroid hormone receptor beta1 (TRbeta1) is a hormone-dependent transcription
      factor activated by 3,5,3'-l-triiodothyronine (T3). TRbeta1 functions as a tumor
      suppressor and disturbances of the THRB gene are frequent findings in cancer.
      Translational control mediated by untranslated regions (UTRs) regulates cell
      proliferation, metabolism and responses to cellular stress, processes that are
      involved in carcinogenesis. We hypothesized that reduced TRbeta1 expression in
      clear cell renal cell cancer (ccRCC) results from regulatory effects of TRbeta1
      5' and 3'UTRs on protein translation. We determined TRbeta1 expression and
      alternative splicing of TRbeta1 5' and 3'UTRs in ccRCC and control tissue
      together with expression of the type 1 deiodinase enzyme (coded by DIO1, a
      TRbeta1 target gene). Tissue concentrations of T3 (which are generated in part by
      D1) and expression of miRNA-204 (an mRNA inhibitor for which a putative
      interaction site was identified in the TRbeta1 3'UTR) were also determined.
      TRbeta1 mRNA and protein levels were reduced by 70% and 91% in ccRCC and
      accompanied by absent D1 protein, a 58% reduction in tissue T3 concentration and
      2-fold increase in miRNA-204. Structural analysis of TRbeta1 UTR variants
      indicated that reduced TRbeta1 expression may be maintained in ccRCC by
      posttranscriptional mechanisms involving 5'UTRs and miRNA-204. The tumor
      suppressor activity of TRbeta1 indicates that reduced TRbeta1 expression and
      tissue hypothyroidism in ccRCC tumors is likely to be involved in the process of
      carcinogenesis or in maintaining a proliferative advantage to malignant cells.

PMID- 20691261
TI  - Role of IL-6 trans-signaling in CCl4induced liver damage.
AB  - Interleukin-6 (IL-6) plays an important role in liver regeneration and protection
      against liver damage. In addition to IL-6 classic signaling via membrane bound
      receptor (mIL-6R), IL-6 signaling can also be mediated by soluble IL-6R (sIL-6R)
      thereby activating cells that do not express membrane bound IL-6R. This process
      has been named trans-signaling. IL-6 trans-signaling has been demonstrated to
      operate during liver regeneration. We have developed methods to specifically
      block or mimic IL-6 trans-signaling. A soluble gp130 protein (sgp130Fc)
      exclusively inhibits IL-6 trans-signaling whereas an IL-6/sIL-6R fusion protein
      (Hyper-IL-6) mimics IL-6 trans-signaling. Using these tools we investigate the
      role of IL-6 trans-signaling in CCl4 induced liver damage. Blockade of IL-6 trans
      signaling during CCl4 induced liver damage led to higher liver damage, although
      induction of Cyp4502E1 and thus bioactivation of CCl4 was unchanged. Depletion of
      neutrophils resulted in reduced liver transaminase levels irrespective of IL-6
      trans-signaling blockade. Furthermore, IL-6 trans-signaling was important for
      refilling of hepatocyte glycogen stores, which were depleted 24 h after CCl4
      treatment. We conclude that IL-6 trans-signaling via the soluble IL-6R is
      important for the physiologic response of the liver to CCl4 induced chemical
      damage.

PMID- 20691262
TI  - Nuclear localization of cationic solid lipid nanoparticles containing Protamine
      as transfection promoter.
AB  - Protamine has attracted much attention as DNA condenser and nuclear transfer
      enhancer although the excess of hydrophilicity and the strong DNA pack restrain
      its potentialities. In order to overcome this limitation, we added Protamine in
      the composition of solid lipid nanoparticles (SLN-Protamine) and we compared this
      carrier with the same kind of SLN containing Esterquat 1 instead of Protamine
      (SLN-EQ1). Carriers cytotoxicity was assessed on COS-I cells evaluating the cell
      cycle by propidium iodide test, while the transfection efficiency was studied
      using pEGFP as plasmid model. The cell penetrating activity of Protamine inside
      the lipid vectors was evaluated studying cell internalization by confocal
      microscopy using Red Nile-labeled carriers. SLN-Protamine:pDNA showed a mean
      diameter five-times smaller than the size of SLN-EQ1:pDNA and a remarkably lesser
      cytotoxicity. Transfection by SLN-Protamine:pDNA was seven-times more effective
      compared with the Protamine:pDNA polyplexes while no transfection capacity was
      observed for SLN-EQ1:pDNA complexes due to their inability to be internalized
      owing to their larger dimension. Red Nile-SLN-Protamine were localized in
      endocytic-like vesicles into the nuclear membrane suggesting the inclusion of
      Protamine in nano-lipophilic systems may enhance the reduction in the complex
      dimensions, the nuclear pDNA translocation and the pDNA release in the cells.

PMID- 20691263
TI  - A simple method for the preparation of monodisperse protein-loaded microspheres
      with high encapsulation efficiencies.
AB  - A simple method for the preparation of monodisperse protein-loaded polymer
      microspheres is presented in this paper. The method is based on the co-extrusion
      of an internal phase of an aqueous protein solution and an external phase of an
      organic polymer solution through a 200-micron-sized hole. Controlled in the
      correct flow region, this process produces a core-shell-structured laminar liquid
      jet, which breaks to form monodisperse compound liquid droplets. Stabilized in a
      dilute aqueous polyvinyl alcohol (PVA) solution, the droplets are converted into
      solid protein-loaded polymer microspheres through evaporation of the organic
      solvent. Results show that preparation parameters such as polymer concentration,
      total flow rate, flow rate ratio of the aqueous to organic phase have significant
      effects on the mean particle size, particle morphology and protein encapsulation
      efficiency (EE). The results of biodegradation and the protein release
      characteristics of the polymer microspheres are also presented.

PMID- 20691264
TI  - Anticonvulsant effects of a triheptanoin diet in two mouse chronic seizure
      models.
AB  - We hypothesized that in epileptic brains citric acid cycle intermediate levels
      may be deficient leading to hyperexcitability. Anaplerosis is the metabolic
      refilling of deficient metabolites. Our goal was to determine the anticonvulsant
      effects of feeding triheptanoin, the triglyceride of anaplerotic heptanoate. CF1
      mice were fed 0-35% calories from triheptanoin. Body weights and dietary intake
      were similar in mice fed triheptanoin vs. standard diet. Triheptanoin feeding
      increased blood propionyl-carnitine levels, signifying its metabolism. 35%, but
      not 20%, triheptanoin delayed development of corneal kindled seizures. After
      pilocarpine-induced status epilepticus (SE), triheptanoin feeding increased the
      pentylenetetrazole tonic seizure threshold during the chronically epileptic
      stage. Mice in the chronically epileptic stage showed various changes in brain
      metabolite levels, including a reduction in malate. Triheptanoin feeding largely
      restored a reduction in propionyl-CoA levels and increased methylmalonyl-CoA
      levels in SE mice. In summary, triheptanoin was anticonvulsant in two chronic
      mouse models and increased levels of anaplerotic precursor metabolites in
      epileptic mouse brains. The mechanisms of triheptanoin's effects and its efficacy
      in humans suffering from epilepsy remain to be determined.

PMID- 20691265
TI  - Global use of Haemophilus influenzae type b conjugate vaccine.
AB  - Haemophilus influenzae type b (Hib) conjugate vaccines have been underutilized
      globally. We report progress in global use of Hib vaccines included in national
      immunization schedules. The number of countries using Hib vaccine increased from
      89/193 (46%) in 2004 to 158/193 (82%) by the end of 2009. The increase was
      greatest among low-income countries eligible for financial support from the GAVI
      Alliance [13/75 (17%) in 2004, 60/72 (83%) by the end of 2009], and can be
      attributed to various factors. Additional efforts are still needed to increase
      vaccine adoption in lower middle income countries [20/31 (65%) by the end of
      2009].

PMID- 20691266
TI  - Randomized double-blind controlled Phase I/IIa trial to assess the efficacy of
      malaria vaccine PfCS102 to protect against challenge with P. falciparum.
AB  - The aim of this Phase I/IIa double-blind controlled trial was to test the
      efficacy of the sporozoite-based malaria vaccine PfCS 282-383 (PfCS102) to
      protect against Plasmodium falciparum parasitaemia. 16 volunteers were randomized
      to receive twice 30 MUg of PfCS102 formulated in Montanide ISA 720 or ISA 720
      alone (control). Two weeks after 2nd immunization, volunteers were challenged
      using 5 infected mosquitoes. All vaccinees developed antibodies against PfCS102
      versus none control. 8/8 vaccinees and 6/6 controls challenged developed malaria
      parasitaemia. The duration from infection to onset of patent parasitaemia was
      similar in both groups (214 h in vaccinees and 216 in controls). PfCS102 is safe
      and immunogenic but provides no protection against artificial challenge in its
      current formulation.

PMID- 20691267
TI  - An anthrax subunit vaccine candidate based on protective regions of Bacillus
      anthracis protective antigen and lethal factor.
AB  - Studies have confirmed the key role of Bacillus anthracis protective antigen (PA)
      in the US and UK human anthrax vaccines. However, given the tripartite nature of
      the toxin, other components, including lethal factor (LF), are also likely to
      contribute to protection. We examined the antibody and T cell responses to PA and
      LF in human volunteers immunized with the UK anthrax vaccine (AVP). Individual LF
      domains were assessed for immunogenicity in mice when given alone or with PA.
      Based on the results obtained, a novel fusion protein comprising D1 of LF and the
      host cell-binding domain of PA (D4) was assessed for protective efficacy. Murine
      protection studies demonstrated that both full-length LF and D1 of LF conferred
      complete protection against a lethal intraperitoneal challenge with B. anthracis
      STI spores. Subsequent studies with the LFD1-PAD4 fusion protein showed a similar
      level of protection. LF is immunogenic in humans and is likely to contribute to
      the protection stimulated by AVP. A single vaccine comprising protective regions
      from LF and PA would simplify production and confer a broader spectrum of
      protection than that seen with PA alone.

PMID- 20691269
TI  - Expression, purification, and refolding of a recombinant human bone morphogenetic
      protein 2 in vitro.
AB  - In this work, the recombinant human bone morphogenetic protein 2 (rhBMP-2) gene
      was cloned from MG-63 cells by RT-PCR, and the protein was expressed in
      Escherichia coli expression system, purified by Ni-NTA column under denaturing
      conditions and refolded at 4 degrees C by urea gradient dialysis. We found that
      the protein refolding yield was increased with the increase of pH value from pH
      6.0 to pH 9.0. The yield was 42% and 96% at pH 7.4 and pH 9.0, respectively,
      while that at pH 6.0 was only 3.4%. The cell culture results showed that the
      rhBMP-2 refolded at pH 7.4 urea gradient dialysis had higher biological activity
      for MG-63 cell proliferation and differentiation than that refolded at pH 9.0
      since pH 7.4 is closer to the conditions in vivo leading to the formation of
      dimers through the interchain disulfide bond. Moreover, the biological activity
      for MG-63 was promoted with the increase of rhBMP-2 concentration in the cell
      culture medium. This work may be important for the in vitro production and
      biomedical application of rhBMP-2 protein.

PMID- 20691270
TI  - Cholera toxin B subunit-domain III of dengue virus envelope glycoprotein E fusion
      protein production in transgenic plants.
AB  - Envelope glycoprotein E of the dengue virus, which plays a crucial role in its
      entry into host cells, has an immunogenic domain III (EIII, amino acids 297-394),
      which is capable of inducing neutralizing antibodies. However, mice immunized
      with EIII protein without adjuvant elicited low immune responses. To improve low
      immune responses, a DNA fragment, consisting of cholera toxin B subunit and EIII
      gene (CTB-EIII), was constructed and introduced into tobacco plant cells
      (Nicotiana tabacum L. cv. MD609) by Agrobacterium tumefaciens-mediated
      transformation methods. The integration and transcription of CTB-EIII fusion gene
      were confirmed in transgenic plants by genomic DNA PCR amplification and Northern
      blot analysis, respectively. The results of immunoblot analysis with anti-CTB and
      anti-dengue virus antibodies showed the expression of the CTB-EIII fusion protein
      in transgenic plant extracts. Based on the G(M1)-ELISA results, the CTB-EIII
      protein expressed in plants showed the biological activity for intestinal
      epithelial cell membrane glycolipid receptor, G(M1)-ganglioside, and its
      expression level was up to about 0.019% of total soluble protein in transgenic
      plant leaf tissues. The feasibility of using a plant-produced CTB-EIII fusion
      protein to generate immunogenicity against domain III will be tested in future
      animal experiments.

PMID- 20691268
TI  - Tea catechins as inhibitors of receptor tyrosine kinases: mechanistic insights
      and human relevance.
AB  - Receptor tyrosine kinases (RTKs) play important roles in the control of
      fundamental cellular processes, influencing the balance between cell
      proliferation and death. RTKs have emerged as molecular targets for the treatment
      of various cancers. Green tea and its polyphenolic compounds, the catechins,
      exhibit chemopreventive and chemotherapeutic properties in many human cancer cell
      types, as well as in various carcinogenicity models in vivo. Epidemiological
      studies are somewhat less convincing, but some positive correlations have been
      observed. The tea catechins, including (-)-epigallocatechin-3-gallate (EGCG),
      have pleiotropic effects on cellular proteins and signaling pathways. This review
      focuses on the ability of the tea constituents to suppress RTK signaling, and
      summarizes the mechanisms by which EGCG and other catechins might exert their
      protective effects towards dysregulated RTKs in cancer cells. The findings are
      discussed in the context of ongoing clinical trials with RTK inhibitors, and the
      possibility for drug/nutrient interactions enhancing therapeutic efficacy.

PMID- 20691271
TI  - Bordetella pertussis CyaA-RTX subdomain requires calcium ions for structural
      stability against proteolytic degradation.
AB  - Previously, the 126-kDa Bordetella pertussis CyaA pore-forming (CyaA-PF) domain
      expressed in Escherichia coli was shown to retain its hemolytic activity. Here, a
      100-kDa RTX (Repeat-in-ToXin) subcloned fragment (CyaA-RTX) containing a number
      of putative calcium-binding repeats was further investigated. The recombinant
      CyaA-RTX protein, although expressed as a soluble form in a protease-deficient E.
      coli strain BL21(DE3)pLysS, was found to be highly sensitive to proteolytic
      degradation. Interestingly, the addition of calcium ions in a millimolar range
      into the CyaA-RTX preparation significantly prevented the degradation. Moreover,
      levels of proteolytic degradation were dependent on calcium concentrations,
      implying an important role for calcium-binding sites in the RTX subdomain for
      structural stability. Homology-based modeling of the repetitive blocks in the
      CyaA-RTX subdomain supports that this calcium-bound protein folds into a parallel
      beta-roll structure with calcium ions acting as a structural stabilizing bridge.

PMID- 20691272
TI  - Crystal structure of MexZ, a key repressor responsible for antibiotic resistance
      in Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa is responsible for around 10% of all hospital-acquired
      infections and the single most important pathogen of cystic fibrosis lungs. P.
      aeruginosa has high intrinsic and acquired antibiotic resistance, due to the
      extrusion of antibiotics by multidrug efflux pumps. The gene regulator MexZ
      controls the expression of mexXY, the efflux pump responsible for resistance to
      many drugs that are used for treating CF patients. MexZ is shown to be the most
      frequently mutated gene in P. aeruginosa isolated from CF patient lungs,
      confirming its importance in multidrug resistance. Here we present the crystal
      structure of MexZ at 2.9A. Combining the structural information with biochemical
      data on key mutants identified, we provide an explanation for the structural and
      functional consequences of these mutants. This work provides a framework for
      further characterisation of MexZ in order to fully understand its regulation and
      induction.

PMID- 20691273
TI  - New trends in protein expression.

PMID- 20691274
TI  - Predicting EEG single trial responses with simultaneous fMRI and relevance vector
      machine regression.
AB  - The combination of electroencephalography (EEG) and functional Magnetic Resonance
      Imaging (fMRI) has been proposed as a tool to study brain dynamics with both high
      temporal and high spatial resolution. Integration through EEG-fMRI trial-by-trial
      coupling has been proposed as a method to combine the different data sets and
      achieve temporal expansion of the fMRI data (Eichele et al., 2005). To fully
      benefit of this type of analysis simultaneous EEG-fMRI acquisitions are necessary
      (Debener et al., 2006). Here we address the issue of predicting the signal in one
      modality using information from the other modality. We use multivariate Relevance
      Vector Machine (RVM) regression to "learn" the relation between fMRI activation
      patterns and simultaneously acquired EEG responses in the context of a complex
      cognitive task entailing an auditory cue, visual mental imagery and a control
      visual target. We show that multivariate regression is a valuable approach for
      predicting evoked and induced oscillatory EEG responses from fMRI time series.
      Prediction of EEG from fMRI is largely influenced by the overall filtering
      effects of the hemodynamic response function. However, a detailed analysis of the
      auditory evoked responses shows that there is a small but significant
      contribution of single trial modulations that can be exploited for linking
      spatially-distributed patterns of fMRI activation to specific components of the
      simultaneously-recorded EEG signal.

PMID- 20691275
TI  - Domain-general mechanisms of complex working memory span.
AB  - A new fMRI complex working memory span paradigm was used to identify brain
      regions making domain-general contributions to working memory task performance.
      For both verbal and spatial versions of the task, complex working memory span
      performance increased the activity in lateral prefrontal, anterior cingulate, and
      parietal cortices during the Encoding, Maintenance, and Coordination phase of
      task performance. Meanwhile, overlapping activity in anterior prefrontal and
      medial temporal lobe regions was associated with both verbal and spatial recall
      from working memory. These findings help to adjudicate several contested issues
      regarding the executive mechanisms of working memory, the separability of short
      term and working memory in the verbal and spatial domains, and the relative
      contribution of short-term and long-term memory mechanisms to working memory
      capacity. The study also provides a vital bridge between psychometric and
      neuroimaging approaches to working memory, and constrains our understanding of
      how working memory may contribute to the broader landscape of cognitive
      performance.

PMID- 20691276
TI  - Plant microRNAs: an insight into their gene structures and evolution.
AB  - MicroRNAs (miRNAs) are 21-23 nucleotide (nt) non-coding RNAs that play a key role
      in regulating the expression of protein-coding genes at post-transcriptional
      levels in plants and animals. MiRNA genes, which serve as genetic buffers and
      regulators, are primarily located in the intergenic regions of the plant genome.
      The similar structure of a miRNA promoter to that of a protein-coding gene
      signifies the likely origin of miRNA genes from the latter. Imperfect "inverted
      repeats", the hallmark of miRNA genes that defines the asymmetry of the "stem
      loop" region of the miRNA precursors (pre-miRNAs), reflect the evolution of miRNA
      genes from the inverted duplication of their target genes over a long period of
      time. The deep conservation of most miRNAs and the presence of some of the non
      conserved, species-specific miRNAs among various plant species demonstrate a
      continuous, but frequently an uneven evolutionary process of miRNA genes. Thus,
      duplication, inversion, mutation, amplification, and other types of genetic drift
      from protein-coding genes might be the primary events in the genesis and
      evolution of the miRNA genes. Subsequent co-evolution of the miRNA genes and
      their target genes ensures the maintenance and the fine-tuning nature of a
      dynamic gene regulatory network governed by miRNAs in plants.

PMID- 20691277
TI  - Phox2b, congenital central hypoventilation syndrome and the control of
      respiration.
AB  - Neural networks in the hindbrain generate the pattern of motor activity that
      sustains breathing in mammals. Over the last years, increasing knowledge of the
      development and the molecular signatures of different classes of hindbrain
      neurons has led to a better definition of the neuronal circuits essential for
      adequate breathing. Here, we review how, on the basis of earlier clinical and
      genetic studies of a human respiratory disease, evidence from neurophysiology and
      mouse genetics has led to the conclusion that a restricted number of neuronal
      types expressing and depending on the Phox2b transcription factor play crucial
      roles in the control of respiration. Collectively, these studies argue for the
      paramount importance of a small group of neurons in the rostral medulla termed
      the retrotrapezoid nucleus (RTN) both for the vital drive to breathe afforded by
      CO(2) detection in the brain and for the pacing of respiratory rhythm before
      birth. RTN neurons are now among the molecularly and developmentally best defined
      types of respiratory neurons. Such knowledge will enable new genetic approaches
      towards elucidating how respiratory networks are assembled and configured in
      normal and pathological conditions.

PMID- 20691278
TI  - Highly efficient osteogenic differentiation of human mesenchymal stem cells by
      eradication of STAT3 signaling.
AB  - Human bone marrow-derived mesenchymal stem cells (hMSCs) are promising candidates
      for cellular therapy owing to their multipotency to differentiate into several
      cell lineages. Elucidating the signaling events involved in the response of hMSCs
      to diverse stimulants affecting their differentiation may considerably promote
      their clinical use. In this study, we attempted to illuminate the molecular
      signaling networks involved in bone morphogenetic protein (BMP)-stimulated hMSC
      osteogenic differentiation. We demonstrate that eradication of signal transducers
      and activators of transcription (STAT) signaling considerably enhances BMP
      induced osteogenic differentiation of hMSCs. BMP 2 and 4 are shown for the first
      time to activate the Janus-activated kinase (JAK)-STAT pathway in hMSC.
      Specifically, we reveal that JAK2 mediates STAT3 tyrosine phosphorylation in
      response to the two BMPs, whereas BMP2- and BMP4-induced STAT3 serine
      phosphorylation involves two divergent cascades, namely the mTOR and ERK1/2
      cascades, respectively. Furthermore, elimination of the STAT3 signaling pathway
      by the inhibitors, AG490 or STAT3 siRNA, results in the acceleration and
      augmentation of BMPs-induced osteogenic differentiation, thus proposing a role
      for JAK-STAT signaling as a negative regulator of this process in MSCs. We
      believe that the findings presented in this study may be the basis for the
      development of a useful strategy to better control stem cell fate through
      intervention in molecular signaling networks. Hopefully, such a strategy will
      include the development of more efficient and controllable protocols for hMSC
      differentiation and facilitate their use in regenerative medicine.

PMID- 20691279
TI  - Dorsomorphin and LDN-193189 inhibit BMP-mediated Smad, p38 and Akt signalling in
      C2C12 cells.
AB  - Bone morphogenetic proteins (BMPs) are key regulators of cell fate decisions
      during embryogenesis and tissue homeostasis. BMPs signal through a coordinated
      assembly of two types of transmembrane serine/threonine kinase receptors to
      induce Smad1/5/8 plus non-Smad pathways, such as MAPK and Akt. The recent
      discovery of BMP receptor inhibitors opened new avenues to study specific BMP
      signalling and to delineate this effect from TGF-beta and Activin signalling.
      Here we present comprehensive and quantitative analyses on both canonical and non
      Smad mediated BMP signalling under Dorsomorphin (DM) and LDN-193189 (LDN)
      treatment conditions. We demonstrate for the first time, that both compounds
      affect not only the Smad but also the non-Smad signalling pathways induced by
      either BMP2, BMP6 or GDF5. The activation of p38, ERK1/2 and Akt in C2C12 cells
      was inhibited by DM and LDN. In addition "off-target" effects on all branches of
      BMP non-Smad signalling are presented. From this we conclude that the inhibition
      of BMP receptors by DM and more efficiently by LDN-193189 affects all known BMP
      induced signalling cascades.

PMID- 20691280
TI  - Biological effects of propionic acid in humans; metabolism, potential
      applications and underlying mechanisms.
AB  - Undigested food is fermented in the colon by the microbiota and gives rise to
      various microbial metabolites. Short-chain fatty acids (SCFA), including acetic,
      propionic and butyric acid, are the principal metabolites produced. However, most
      of the literature focuses on butyrate and to a lesser extent on acetate;
      consequently, potential effects of propionic acid (PA) on physiology and
      pathology have long been underestimated. It has been demonstrated that PA lowers
      fatty acids content in liver and plasma, reduces food intake, exerts
      immunosuppressive actions and probably improves tissue insulin sensitivity. Thus
      increased production of PA by the microbiota might be considered beneficial in
      the context of prevention of obesity and diabetes type 2. The molecular
      mechanisms by which PA may exert this plethora of physiological effects are
      slowly being elucidated and include intestinal cyclooxygenase enzyme, the G
      protein coupled receptors 41 and 43 and activation of the peroxisome proliferator
      activated receptor gamma, in turn inhibiting the sentinel transcription factor NF
      kappaB and thus increasing the threshold for inflammatory responses in general.
      Taken together, PA emerges as a major mediator in the link between nutrition, gut
      microbiota and physiology.

PMID- 20691281
TI  - Diagnosis-specific characteristics of ventricular tachycardia in children with
      structurally normal hearts.
AB  - BACKGROUND: Improved mechanistic insights and clinical tools provide increasing
      diagnostic refinement for ventricular tachycardia in young patients with
      structurally normal hearts, yielding potentially important prognostic and
      management implications. OBJECTIVE: The purpose of this study was to survey the
      clinical characteristics and outcomes of otherwise healthy children with
      ventricular tachycardia (VT) who were classified according to contemporary
      diagnostic criteria. METHODS: A single-center retrospective review of patients
      younger than 18 years of age with VT diagnosed between January 1980 and December
      2005 was undertaken. Patients with significant systemic illness or with
      underlying structural or functional heart disease were excluded. RESULTS: A total
      of 77 patients met inclusion criteria and were grouped as follows: accelerated
      idioventricular rhythm (AIVR; n = 19), right ventricular tachycardia (RVT; n =
      30), left ventricular tachycardia (LVT; n = 23), and catecholamine sensitive
      polymorphic VT (CPVT; n = 5). AIVR patients were youngest at diagnosis and had
      the most benign natural history, while the opposite was true of CPVT patients.
      Ablation was attempted in 2/30 RVT (50% success) and 10/23 LVT (80% success)
      patients. Severe cardiac events occurred in 3/23 LVT (no deaths) and 2/5 CPVT
      (one death) patients. CONCLUSION: The natural history and appropriate management
      of VT in young patients with structurally normal hearts are highly dependent on
      the specific diagnosis. LVT and CPVT are associated with significantly greater
      morbidity and mortality than AIVR and RVT.

PMID- 20691282
TI  - Preexcitation unmasked after successful accessory atrioventricular connection
      ablation: what is the mechanism?

PMID- 20691283
TI  - Presence of left ventricular contractile reserve predicts midterm response to
      cardiac resynchronization therapy--results from the LOw dose DObutamine stress
      echo test in Cardiac Resynchronization Therapy (LODO-CRT) trial.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) is effective in selected
      patients with heart failure (HF). Nevertheless, the nonresponder rate remains
      high. The low-dose dobutamine stress-echo (DSE) test detects the presence of left
      ventricular (LV) contractile reserve (LVCR) in HF patients of any etiology and
      may be useful in predicting response to resynchronization. OBJECTIVE: The purpose
      of this study was to present the results of the LODO-CRT trial, which evaluated
      whether LVCR presence at baseline increases the chances of response to CRT.
      METHODS: LODO-CRT is a multicenter prospective study that enrolled CRT candidates
      according to guidelines. LVCR presence was defined as an LV ejection fraction
      increase >5 units during DSE test. CRT response is assessed at 6-month follow-up
      as an LV end-systolic volume reduction >=10%. RESULTS: Two hundred seventy-one
      patients were enrolled. The DSE test was feasible without complications in 99% of
      patients. Nine patients died from noncardiac disease, and 31 presented inadequate
      data. Two hundred thirty-one patients were included in the analysis. Mean patient
      age was 67 +/- 10 years; 95% were in New York Heart Association class III, and
      42% had HF of ischemic etiology. Mean QRS and LV ejection fraction were 147 +/-
      25 ms and 27% +/- 6%, respectively. LVCR presence was found in 185 subjects
      (80%). At follow-up, 170 (74%) patients responded to CRT, 145/185 in the group
      with LVCR (78%) and 25/46 (54%) in the group without LVCR. Difference in
      responder proportion to CRT was 24% (P <.001). Reported test sensitivity is 85%.
      CONCLUSION: The DSE test in CRT candidates is safe and feasible. LVCR presence at
      baseline increases the chances of response to CRT.

PMID- 20691284
TI  - Neuropsychological decline after catheter ablation of atrial fibrillation.
AB  - BACKGROUND: Cerebral embolic events represent recognized side effects after
      catheter ablation in the treatment of recurrent atrial fibrillation (AF).
      OBJECTIVE: The study was performed to analyze the neuropsychological outcome and
      to detect new embolic ischemic brain lesions after therapeutic left atrial
      catheter ablation of AF. METHODS: We enrolled 23 patients with recurrent AF who
      underwent elective circumferential pulmonary vein isolation. The primary endpoint
      was the neuropsychological outcome 3 months after intervention in contrast to the
      results of non-AF controls (n = 23) without ablation and in covariance of
      baseline performance. Cerebral diffusion-weighted magnetic resonance imaging
      (DWI) was performed in 21 AF patients at baseline, 2-4 days, and 3 months after
      intervention. RESULTS: In 3/21 patients (14.3%), new ischemic lesions were
      detected on DWI shortly after intervention. In one patient, a territorial middle
      cerebral artery infarct occurred with severe clinical symptoms. The other two
      patients represented clinically silent small lesions. In contrast to the control
      group and in covariance of baseline performance, the ablation group showed worse
      neuropsychological outcome in verbal memory (one of five cognitive domains) with
      an effect size of d = 0.93[t (.05; 42) = -3.53; P < .001; false discovery rate
      (FDR)(crit) <= .01]. CONCLUSION: Adverse neuropsychological changes after left
      atrial catheter ablation are verifiable in verbal memory and, conjoined with
      ischemic brain lesions on DWI, might represent cerebral side effects of this
      procedure.

PMID- 20691285
TI  - POLG exon 22 skipping induced by different mechanisms in two unrelated cases of
      Alpers syndrome.
AB  - The POLG genes were sequenced in two unrelated patients presenting with Alpers
      syndrome. The novel c.3626_3629dupGATA and the c.3643+2T>C alleles were
      associated in trans with p.A467T and p.[W748S;E1143G], respectively. POLG
      transcripts from skin fibroblasts showed complete exon 22 skipping for patient 2,
      but surprisingly partial exon 22 skipping from the c.3626_3629dupGATA for patient
      1. The creation of a putative exonic splicing silencer could be responsible for
      the splicing anomaly observed in patient 1. Both c.3643+2T>C and
      c.3626_3629dupGATA create a premature termination codon and a low polymerase
      gamma activity in skin fibroblasts is responsible for the severe phenotype in
      these patients.

PMID- 20691286
TI  - Toll-like receptor-3-induced mitochondrial dysfunction in cultured human
      hepatocytes.
AB  - Several studies have shown the presence of liver mitochondrial dysfunction during
      sepsis. TLR3 recognizes viral double-stranded RNA and host endogenous cellular
      mRNA released from damaged cells. TLR3 ligand amplifies the systemic
      hyperinflammatory response observed during sepsis and in sepsis RNA escaping from
      damaged tissues/cells may serve as an endogenous ligand for TLR3 thereby
      modulating immune responses. This study addressed the hypothesis that TLR3 might
      regulate mitochondrial function in cultured human hepatocytes. HepG2 cells were
      exposed to TLR-3 ligand (dsRNA--polyinosine-polycytidylic acid; Poly I:C) and
      mitochondrial respiration was measured. Poly I:C induced a reduction in maximal
      mitochondrial respiration of human hepatocytes which was prevented partially by
      preincubation with cyclosporine A (a mitochondrial permeability transition pore
      opening inhibitor). Poly-I:C induced activation of NF-kappaB, and the
      mitochondrial dysfunction was accompanied by caspase-8 but not caspase-3
      activation and by no major alterations in cellular or mitochondrial
      ultrastructure.

PMID- 20691287
TI  - Contraction stresses in dental composites adjacent to and at the bonded interface
      as measured by crack analysis.
AB  - The objective of this study was to calculate stresses produced by polymerization
      contraction in regions surrounding a dental resin composite restoration. Initial
      cracks were made with a Vickers indenter at various distances from the edge of a
      cylindrical hole in a soda-lime glass disk. Indentation crack lengths were
      measured parallel to tangents to the hole edge. Resin composites (three brands)
      were placed in the hole and polymerized (two light irradiation protocols) at
      equal radiation exposures. The crack lengths were re-measured at 2 and 10 min
      after irradiation. Radial tensile stresses due to polymerization contraction at
      the location of the cracks (sigma(crack)) were calculated from the incremental
      crack lengths and the fracture toughness K(c) of the glass. Contraction stresses
      at the composite-glass bonded interface (sigma(interface)) were calculated from
      sigma(crack) on the basis of the simple mechanics of an internally pressurized
      thick-walled cylinder. The greater the distance or the shorter the time following
      polymerization, the smaller was sigma(crack). Distance, material, irradiation
      protocol and time significantly affected sigma(crack). Two-step irradiation
      resulted in a significant reduction in the magnitude of sigma(interface) for all
      resin composites. The contraction stress in soda-lime glass propagated
      indentation cracks at various distances from the cavity, enabling calculation of
      the contraction stresses.

PMID- 20691288
TI  - Biodegradable and synthetic membranes for the expansion and functional
      differentiation of rat embryonic liver cells.
AB  - The insufficient availability of donor organs for orthotopic liver
      transplantation worldwide has urgently increased the requirement for new
      therapies for acute and chronic liver disease. The creation of an unlimited
      source of donor cells for hepatocyte transplantation therapy and pharmaceutical
      applications may be the isolation and expansion of liver progenitor cells or stem
      cells. Here we report the expansion and functional differentiation of rat
      embryonic liver cells on biodegradable and synthetic polymeric membranes in
      comparison with traditional substrates, such as collagen and polystyrene culture
      dishes. Membranes prepared from chitosan and modified polyetheretherketone were
      used for the culture of liver progenitor cells derived from rat embryonic liver.
      Cells proliferated, with a significant increase in their number within 8-11 days.
      The cells displayed functional differentiation showing urea synthesis, albumin
      production and diazepam biotransformation on all substrates investigated. In
      particular, on a chitosan membrane liver-specific functions were expressed at
      significantly higher levels for prolonged times compared with other synthetic
      membranes, utilizing traditional substrates (collagen and PSCD) as references.
      These results demonstrate that chitosan membranes offer cells favourable
      conditions to promote the expansion and functional differentiation of embryonic
      liver cells that could be effectively used in liver tissue engineering and in
      pharmaceutical applications.

PMID- 20691289
TI  - Fabrication and characterization of hierarchically organized nanoparticle
      reinforced nanofibrous composite scaffolds.
AB  - Two different techniques were used to fabricate nanoparticle-reinforced
      nanofibrous scaffolds with different organizations of the minerals. First, a
      three-dimensional (3D) cylindrical nanofibrous scaffold made of poly-L-lactide
      and poly(L-lactide)/collagen (1:1) was fabricated using a modified
      electrospinning method. An alternating dipping method and a flow version of it
      were used to mineralize the 3D scaffolds. Flow mineralization was found to
      significantly improve the distribution of the mineral nanoparticles throughout
      the 3D nanofibrous scaffold, while mineral nanoparticles were found only on the
      periphery of the static mineralized scaffold. As a result of the mineral
      nanoparticle distribution, the compressive strength and modulus of the flow
      mineralized scaffold was found to be significantly greater than that of the
      static mineralized scaffold, despite having a lower mineral content. Energy
      dispersive X-ray analysis and X-ray diffraction studies suggest that the mineral
      was composed of heterogeneous phases of calcium phosphates. This study
      demonstrates the importance of hierarchical and deliberate organization of the
      nanocomponents to optimize the mechanical properties, as is often found in
      nature.

PMID- 20691290
TI  - Simplifying minilap cholecystectomy.

PMID- 20691291
TI  - Risk factors for operative mortality and morbidity in gastric cancer undergoing
      D2-gastrectomy.
AB  - AIM: We have assessed the risk factors for mortality and morbidity subsequent to
      D2-gastrectomy in gastric cancer cases. PATIENTS AND METHOD: The records (age,
      gender, comorbidity, ASA score, POSSUM score, type of gastrectomy, additional
      organ resection and pathologic TNM stage) were reviewed in 49 cases of D2
      gastrectomies (between 2003 and 2008) retrospectively. RESULTS: Mean age was 60.4
      (range: 35-82). The factors of comorbidity (n=38) in 27 patients. The average
      quantity of lymph nodes was 21.2 (range: 16-31) in D2 dissections. The rate of
      mortality was 8.2% (4/49). All the patients who died had major comorbid diseases
      and all were submitted to total gastrectomy. Twenty-one morbidities were detected
      in 13 patients [morbidity rate was 26.5% (13/49)]. We have observed a nearly
      statistically significant (p=0.074) disadvantage of total gastrectomy versus
      subtotal gastrectomy [those who died had undergone total gastrectomy, and the
      morbidity rates were 36.4% vs 14.8%] in concordance with literature. CONCLUSION:
      In these studies, we have observed that our mortality (8.2%) and morbidity
      (26.5%) rates are in concordance with the data from medical literature, and
      POSSUM scores are the only parameter in positive statistical correlation with
      mortality. Preoperative and postoperative resuscitation are of great importance
      if the patients have POSSUM score >20.

PMID- 20691292
TI  - Surgical pathology is a predictor of outcome in post-operative lymph leakage.
AB  - BACKGROUND: Post-operative lymph leak is a potentially serious complication which
      may contribute to fluid and electrolyte imbalance, malnutrition and an increase
      risk of sepsis and mortality. We aimed to study the use of TPN in the treatment
      of post-operative lymph leak. METHODS: Retrospective review of prospectively
      collected clinical database comprising patients with post-operative lymph leak
      treated with TPN collected over 1998-2006. An analysis of morbidity and mortality
      was performed. RESULTS: 36 patients developed lymph leak following radical neck
      dissection (n = 10), Whipples procedure (n = 13), oesophagectomy (n = 10) and
      pulmonary/vascular/retroperitoneal (n = 3) surgery. The survival to discharge was
      89%. The mortality rate in patients with chylothorax following oesophagectomy was
      30% (three out of ten). The majority of patients (67%, 24 out of 36) with lymph
      leak settled on TPN alone. The overall re-intervention rate was 20%. Of the seven
      survivors after oesophagectomy, five underwent re-intervention thoracic surgery
      (two also had ischaemic perforation of gastric remnant needing revision surgery).
      Overall, the re-intervention rate in all patients undergoing oesophageal surgery
      is 60%. CONCLUSION: Most patients with post-operative lymph leak receiving TPN
      alone survived. It is rare for re-operation to be necessary in patients who have
      lymph leaks in the neck or retroperitoneum. Re-operative intervention is more
      commonly performed in lymph leak after oesophagectomy.

PMID- 20691293
TI  - Predictors of length of stay in patients having elective colorectal surgery
      within an enhanced recovery protocol.
AB  - BACKGROUND: Enhanced recovery after surgery (ERAS) pathways has been shown to
      minimize the duration of hospital stay. The aim of this study was to identify
      which factors have the greatest impact at reducing the length of stay within an
      enhanced recovery programme. METHODS: A retrospective case note review of
      patients undergoing open elective colorectal resections between August 2007 and
      May 2009 was performed. Data on numerous pre, peri and postoperative variables
      were collected. Postoperative complications, readmissions, length of stay and
      fitness for discharge were recorded. Using logistic regression analysis,
      univariate and multivariate analysis of predictors for a shorter hospital stay
      was performed. Odd ratios and ninety-five percent confidence intervals were
      calculated and a p-value of less than 0.05 was significant. RESULTS: There were
      231 patients, of which 130 were female. Median age was 68 (IQR 56-76) years.
      Median length of stay was 6 (IQR 5-9) days. On multivariate analysis, ASA grade
      (OR 2.85 (95%CI 1.17-6.89), p = 0.040), the avoidance of oral opiates in the
      postoperative period (OR 0.39 (95%CI 0.18-0.84), p = 0.016) and the duration of
      use of epidurals for postoperative analgesia (OR 0.44 (95%CI 0.12-0.94), p =
      0.023) were found to be significant predictors of reduced hospital stay.
      CONCLUSION: Lower ASA grade, use of epidurals and avoidance of regular oral
      opiates are associated with an earlier discharge in an ERAS programme.

PMID- 20691294
TI  - Meta-analysis of the use of glyceryl trinitrate ointment after haemorrhoidectomy
      as an analgesic and in promoting wound healing.
AB  - INTRODUCTION: Glyceryl Trinitrate (GTN) ointment has been used to treat anal
      fissure and pain relief in haemorrhoids, but the value of its use post
      haemorrhoidectomy as an analgesic and in wound healing is unclear. The side
      effect of headache has often been an associated problem. Therefore, a meta
      analysis of randomised controlled trials was carried out investigating the role
      of GTN post-haemorrhoidectomy as an analgesic, its role in would healing and the
      unwanted incidence of headache. METHOD: A structured literature search from 1966
      to 2009, both paper and online, with no language barrier was carried out. 760
      papers were identified and 5 randomised control trials which met the entry
      criteria were included in this study. RESULTS: A total of 333 patients were
      included in the meta-analysis. The results revealed that GTN ointment was
      statistically significant in reducing pain on Day 3 and 7 compared to the placebo
      group. Day 3 shows a pain score of - 1.51 (p value of 0.029) and Day 7 by - 1.66
      (p value of 0.014) respectively. However, it was not significant in reducing pain
      on Day 1. The Odds ratio for wound healing after GTN treatment at 3 weeks was
      3.57 (P < 0.0001) when compared to the placebo group. Side effect of headache was
      not statistically significant. CONCLUSION: This meta-analysis has shown that GTN
      ointment used post-haemorrhoidectomy has a significant analgesic effect in the
      intermediate time period (ie. Days 3-7). It also significantly improved wound
      healing at 3 weeks.

PMID- 20691296
TI  - Identifying cost-effective treatment with raloxifene in postmenopausal women
      using risk algorithms for fractures and invasive breast cancer.
AB  - INTRODUCTION: The National Osteoporosis Foundation (NOF) recommends considering
      treatment in women with a 20% or higher 10-year probability of a major fracture.
      However, raloxifene reduces both the risk of vertebral fractures and invasive
      breast cancer so that raloxifene treatment may be clinically appropriate and cost
      effective in women who do not meet a 20% threshold risk. The aim of this study
      was to identify cost-effective scenarios of raloxifene treatment compared to no
      treatment in younger postmenopausal women at increased risk of invasive breast
      cancer and fracture risks below 20%. METHOD: A micro-simulation model populated
      with data specific to American Caucasian women was used to quantify the costs and
      benefits of 5-year raloxifene treatment. The population evaluated was selected
      based on 10-year major fracture probability as estimated with FRAX(r) being below
      20% and 5-year invasive breast cancer risk as estimated with the Gail risk model
      ranging from 1% to 5%. RESULTS: The cost per QALY gained ranged from US $22,000
      in women age 55 with 5% invasive breast cancer risk and 15-19.9% fracture
      probability, to $110,000 in women age 55 with 1% invasive breast cancer risk and
      5-9.9% fracture probability. Raloxifene was progressively cost-effective with
      increasing fracture risk and invasive breast cancer risk for a given age cohort.
      At lower fracture risk in combination with lower invasive breast cancer risk or
      when no preventive raloxifene effect on invasive breast cancer was assumed, the
      cost-effectiveness of raloxifene worsened markedly and was not cost-effective
      given a willingness-to-pay of US $50,000. At fracture risk of 15-19.9% raloxifene
      was cost-effective also in women at lower invasive breast cancer risk.
      CONCLUSIONS: Raloxifene is potentially cost-effective in cohorts of young
      postmenopausal women, who do not meet the suggested NOF 10-year fracture risk
      threshold. The cost-effectiveness is contingent on their 5-year invasive breast
      cancer risk. The result highlights the importance of considering a woman's full
      risk profile when considering anti-osteoporosis treatment.

PMID- 20691297
TI  - Towards quantitative 3D imaging of the osteocyte lacuno-canalicular network.
AB  - Osteocytes are the most abundant cells in bone and the only cells embedded in the
      bone mineral matrix. They form an extended, three-dimensional (3D) network, whose
      processes interconnecting the cell bodies reside in thin canals, the canaliculi.
      Together with the osteocyte lacunae, the canaliculi form the lacuno-canalicular
      network (LCN). As the negative imprint of the cellular network within bone
      tissue, the LCN morphology is considered to play a central role for bone
      mechanosensation and mechanotransduction. However, the LCN has neither been
      visualized nor quantified in an adequate way up to now. On this account, this
      article summarizes the current state of knowledge of the LCN morphology and then
      reviews different imaging methods regarding the quantitative 3D assessment of
      bone tissue in general and of the LCN in particular. These imaging methods will
      provide new insights in the field of bone mechanosensation and
      mechanotransduction and thus, into processes of strain sensation and
      transduction, which are tightly associated with osteocyte viability and bone
      quality.

PMID- 20691298
TI  - Bimodal distribution of osteocyte lacunar size in the human femoral cortex as
      revealed by micro-CT.
AB  - Tomographic reconstructions of sections of human femoral bone were created from x
      ray data sets taken using synchrotron radiation of 26.4 keV and with isotropic
      voxels 1.47 MUm on a side. We demonstrate that it is possible to segment the data
      to isolate both the osteocyte lacunae and the Haversian canals in the bone as
      well as identifying osteon boundaries. From this information a wealth of data
      relating to bone structure becomes available. The data were used to map the
      spatial positions of the osteocyte lacunae, relative to the Haversian canals and
      of the osteon boundaries. The dimensions and volume of the imaged osteocyte
      lacunae were measured for close to 10,000 lacunae. When averaged over the 11
      osteons measured, osteocyte densities varied from 4*10(4)per mm(3) close to the
      Haversian canals to about 9*10(4)per mm(3) at 80% of osteon radius. The nearest
      neighbour distances varied from 10 MUm to 40 MUm with a peak at 23 MUm and an
      approximately normal distribution. The distribution of lacunar long-axis length
      was also approximately normal with a small positive skew and the peak value was 8
      MUm with a range from 3 MUm to 20 MUm. The most significant finding from this
      study was that the distribution of the measured volumes of osteocyte lacunae had
      two distinct peaks, one at 200 MUm(3) and a second at 330 MUm(3).

PMID- 20691300
TI  - On-statin cholesteryl ester transfer protein mass and risk of recurrent coronary
      events (from the pravastatin or atorvastatin evaluation and infection therapy
      thrombolysis in myocardial infarction 22 [PROVE IT-TIMI 22] study).
AB  - Although cholesteryl ester transfer protein (CETP) plays an important role in
      human lipoprotein metabolism, its relation to coronary artery disease remains
      controversial. The present study evaluated the relation between on-statin CETP
      mass and recurrent coronary events. The plasma CETP mass, measured after 4 months
      of statin therapy, was quantified in 3,218 patients enrolled in the Pravastatin
      or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial
      Infarction 22 (PROVE IT-TIMI 22) study. Of the 3,218 patients, 150 experienced
      the combined end point of recurrent myocardial infarction or death from coronary
      causes during a mean follow-up of 1.8 years. An increasing on-statin CETP mass
      was inversely related to the risk of coronary events in both unadjusted (hazard
      ratio [HR] per SD increase 0.77, 95% confidence interval 0.65 to 0.92, p = 0.005)
      and fully adjusted (HR per SD increase 0.81, 95% confidence interval 0.67 to
      0.98, p = 0.027) analyses that included traditional cardiovascular risk factors.
      A similar trend was observed across increasing CETP mass quartiles (p trend =
      0.07). A significant interaction between the CETP mass and on-treatment low
      density lipoprotein (LDL) cholesterol was noted (p interaction = 0.007). A CETP
      mass greater than the median was associated with a decreased risk in patients
      with LDL cholesterol less than the median of 80 mg/dl (HR 0.52, 95% confidence
      interval 0.31 to 0.89, p = 0.02), but not in patients with LDL cholesterol
      greater than the median. In conclusion, an increasing on-statin CETP mass was
      inversely related to the coronary outcomes in this large clinical trial-based
      cohort, particularly among those with low LDL cholesterol levels. This finding is
      consistent with CETP facilitating reverse cholesterol transport in the setting of
      robust LDL clearance and might have important implications for efforts to
      optimally target patients with pharmacologic CETP inhibition.

PMID- 20691301
TI  - A proposed clinical model for efficient utilization of invasive coronary
      angiography.
AB  - More than 1/4 of patients who undergo invasive coronary angiography are found to
      have no visible or nonobstructive (<50% stenosis) coronary artery disease (CAD).
      With the rapid evolution of noninvasive imaging for CAD diagnosis, avoiding
      invasive coronary angiography in patients unlikely to require coronary
      revascularization is desirable. We undertook to develop a clinical prediction
      tool to identify patients with a low likelihood of obstructive (> or =50%
      stenosis) CAD. The derivation cohort included 24,637 patients with a diagnosis of
      "stable angina" or "acute coronary syndrome" referred for first cardiac
      catheterization in the province of British Columbia, Canada. The model was
      validated using an external dataset from the province of Alberta and comprised
      18,606 patients. Seven variables (female gender, age <50 years, atypical Canadian
      Cardiovascular Society angina class, absence of ST-segment change on
      electrocardiogram, lifelong nonsmoking, and absence of diabetes and
      hyperlipidemia) were associated with the angiographic finding of "no or
      nonobstructive CAD." The c-statistics for the derivation model were 0.76 and 0.74
      using the validation dataset. In conclusion, this simple clinical prediction
      tool, applied to patients for whom determination of coronary anatomy was
      clinically indicated, identifies patients who have a low likelihood of
      obstructive CAD. The patient population identified by this tool may represent a
      population best suited to a noninvasive diagnostic strategy.

PMID- 20691302
TI  - Usefulness of computed tomographic coronary angiography in patients with acute
      chest pain with and without high-risk features.
AB  - The accuracy of 64-slice computed tomographic coronary angiography (CTA) and its
      ability to direct revascularization in patients with acute chest pain syndrome
      (ACPS) was investigated. A total of 107 patients with ACPS presenting to the
      emergency department and referred to cardiology were prospectively enrolled and
      underwent CTA. From the clinical features, the patients were categorized as
      having high-risk acute coronary syndrome features or no high-risk features. At
      the treating physician's discretion, the patients underwent risk stratification
      with either invasive coronary angiography (ICA) or technetium-99m single photon
      emission computed tomography. All tests were interpreted by experts unaware of
      the clinical information. All 52 patients with high-risk acute coronary syndrome
      features underwent ICA. Of the 55 patients with no high-risk features, 36
      underwent single photon emission computed tomography and 19 underwent ICA. The
      patients were followed up until a decision regarding revascularization was made.
      Compared with ICA, the operating characteristics of CTA (per-patient analysis)
      were excellent, with a sensitivity of 98% (95% confidence interval [CI] 87% to
      100%), specificity of 100% (95% CI 85% to 100%), positive predictive value of
      100% (95% CI 90% to 100%), and negative predictive value of 97% (95% CI 80% to
      100%). The agreement between CTA and routine testing (single photon emission
      computed tomography or ICA) was very good (kappa = 0.94). CTA correctly
      identified 40 patients (100%) who underwent revascularization and 61 (91.0%) who
      were treated medically (kappa = 0.88, 95% CI 0.79 to 0.97). In conclusion, CTA
      might represent a single modality that could be used to triage a wide spectrum of
      patients with ACPS and could have the potential to rule out coronary disease and
      identify those who might require revascularization.

PMID- 20691303
TI  - Usefulness of neutrophil to lymphocyte ratio in predicting short- and long-term
      mortality after non-ST-elevation myocardial infarction.
AB  - Neutrophil/lymphocyte ratio (NLR) is the strongest white blood cell predictor of
      adverse outcomes in stable and unstable coronary artery syndromes. The aim of our
      study was to explore the utility of NLR in predicting long-term mortality in
      patients with non-ST-segment elevation myocardial infarction (NSTEMI).
      Consecutive patients with NSTEMI at Staten Island University Hospital were
      evaluated for study inclusion. Of the 1,345 patients with NSTEMI admitted from
      September 2004 to September 2006, 619 qualified for study inclusion. Survival
      analysis, stratified by NLR tertiles, was used to evaluate the predictive value
      of average inpatient NLR levels. Four-year vital status was accessed with
      electronic medical records and Social Security Death Index. Patients in the
      highest NLR tertile (NLR >4.7) had a higher 4-year mortality rate (29.8% vs 8.4%)
      compared to those in the lowest tertile (NLR <3, Wilcoxon chi-square 34.64, p
      <0.0001). After controlling for Global Registry of Acute Coronary Events risk
      profile scores, average NLR level remained a significant predictor of inpatient
      and 4-year mortality. Hazard ratios per unit increase of average NLR (log)
      increased by 1.06 (p = 0.0133) and 1.09 (p = 0.0006), respectively. In
      conclusion, NLR is an independent predictor of short-term and long-term
      mortalities in patients with NSTEMI with an average NLR >4.7. We strongly suggest
      the use of NLR rather than other leukocyte parameters (e.g., total white blood
      cell count) in risk stratification of the NSTEMI population.

PMID- 20691304
TI  - Usefulness of plasma tissue inhibitors of metalloproteinases as markers of
      prognosis after acute myocardial infarction.
AB  - Alterations in the balance of matrix metalloproteinase to tissue inhibitor of
      metalloproteinase (TIMP) are seen after acute myocardial infarction (AMI) and are
      associated with adverse left ventricular remodeling and prognosis in this
      setting. We aimed to investigate the association between TIMP levels and the
      occurrence of major adverse cardiac events (MACEs) after AMI. We measured plasma
      TIMP-1, -2, and -4 levels in 1,313 patients presenting with AMI. Subjects were
      followed over a median period of 520 days for the occurrence of MACEs. Clinical
      risk was assessed using the Global Registry of Acute Coronary Events (GRACE)
      score. All TIMP levels correlated with patient age and inversely with estimated
      glomerular filtration rate (all p values <0.001). Levels were higher in women
      versus men (p <0.001) and in subjects with a history of diabetes (TIMP-1, p
      <0.001; TIMP-2, p = 0.002; TIMP-4, p <0.001) or hypertension (TIMP-1, p = 0.031;
      TIMP-2, p <0.001; TIMP-4, p <0.001). TIMP-1 and TIMP-4 were higher in subjects
      with previous MI or angina (p <0.001). TIMP levels increased incrementally with
      quartiles of GRACE score (p <0.001). All TIMPs showed univariate association with
      the occurrence of MACEs (p <0.001). Areas under the receiver operator
      characteristic curve for prediction of MACE at 1 year were 0.61 for TIMP-1, 0.57
      for TIMP-2, and 0.64 for TIMP-4. Combination of TIMPs with GRACE risk score
      revealed a greater area under the curve than GRACE score alone (0.72 vs 0.69, p =
      0.0015). On multivariable Cox proportional hazards analysis, GRACE score (p
      <0.001) and plasma TIMPs (log TIMP-1, p = 0.017; log TIMP-2, p <0.001; log TIMP
      4, p = 0.011) independently predicted MACEs. Using Kaplan-Meier analysis, the
      risk of MACEs increased incrementally with the number of TIMPs above their
      respective median (p <0.001 for all comparisons, log-rank test). In conclusion,
      higher plasma TIMP-1, -2, and -4 after AMI are associated with MACEs and provide
      additional prognostic information to that obtained from GRACE clinical risk
      scores alone.

PMID- 20691305
TI  - Usefulness of radial strain mapping by multidetector computer tomography to
      quantify regional myocardial function in patients with healed myocardial
      infarction.
AB  - We introduce and evaluate strain mapping by multidetector computer tomography as
      a new noninvasive method for assessment of myocardial function. In patients (n =
      16) with healed myocardial infarction, peak systolic radial strain was measured
      by automated pixel pattern matching analysis of multiple left ventricular 64
      slice multidetector computer tomographic short-axis recordings. For comparison,
      radial strain and myocardial infarct extent were measured by tagged magnetic
      resonance imaging (MRI) and late enhancement MRI, respectively. In a linear mixed
      model analysis, myocardial infarct extent was a strong predictor of segmental
      strain by multidetector computer tomography (beta = -0.44, p <0.0001). Strain was
      significantly different among noninfarcted (0%), nontransmurally infarcted (0% to
      50%), and transmurally infarcted (>50%) segments (p <0.001) and between infarcted
      and noninfarcted border zone segments (p <0.001). There was a close relation
      between strain by multidetector computer tomography and by tagged MRI (mean
      difference -7.4 +/- 11.7%, r = 0.68, p <0.0001). Mean time-to-peak systolic
      strain was 324 +/- 42 ms by multidetector computer tomography and 335 +/- 56 ms
      by tagged MRI (mean difference 11 +/- 40 ms). In conclusion, to our knowledge
      this is the first study to demonstrate that regional myocardial function can be
      quantified by multidetector computer tomographic imaging, indicating that
      assessment of radial strain by multidetector computer tomography might be a
      useful tool in the evaluation of patients with cardiovascular diseases.

PMID- 20691306
TI  - Comparison of everolimus- versus paclitaxel-eluting stents implanted in patients
      with diabetes mellitus as evaluated by three-dimensional intravascular ultrasound
      analysis.
AB  - Previous reports have shown the advantage of paclitaxel compared to limus
      derivative drugs for the treatment of diabetics. A total of 109 diabetics (115
      lesions) treated with everolimus-eluting stents (EESs, n = 58) or paclitaxel
      eluting stents (PESs, n = 55) undergoing 8 to 9 months of follow-up 3-dimensional
      intravascular ultrasound examinations were enrolled. In addition to the standard
      intravascular ultrasound parameters, the percentage of neointimal volume
      (neointimal volume/stent volume) and maximum percentage of cross-sectional
      narrowing (neointimal area/stent area) was calculated. EESs showed a lower
      percentage of neointimal volume (7.2 +/- 7.1% vs 11.7 +/- 11.0%; p = 0.01) and
      maximum percentage of cross-sectional narrowing (22.5 +/- 16.3% vs 29.4 +/-
      19.2%; p = 0.04) than PESs. One case of severe narrowing (lesions with maximum
      percentage of cross-sectional narrowing >60%) in the EES group developed and 6
      cases in the PESs group (p = 0.05). The EESs showed no serial changes for vessel
      or peri-stent plaque during the follow-up period, and PESs showed significant
      increases in vessel and peri-stent plaque. PESs showed significantly greater peri
      stent plaque increase, with a tendency toward greater vessel enlargement than
      EESs. Late acquired incomplete stent apposition was observed in 2 PES cases. The
      major adverse cardiac event rate was comparable < or =2 years. In conclusion,
      EESs showed greater neointimal suppression without significant vessel expansion
      than PESs in diabetic patients. In this small cohort, no significant differences
      were observed in the major adverse cardiac event rate < or =2 years.

PMID- 20691307
TI  - Coronary revascularization strategy and outcomes according to blood pressure
      (from the International Verapamil SR-Trandolapril Study [INVEST]).
AB  - The optimal blood pressure (BP) to prevent major adverse outcomes (death,
      myocardial infarction, and stroke) for patients with hypertension and coronary
      artery disease who have undergone previous revascularization is unknown but might
      be influenced by the type of revascularization procedure. We analyzed data from
      the INternational VErapamil SR-Trandolapril STudy, focusing on the relation
      between BP and the outcomes of 6,166 previously revascularized patients, using
      the 16,410 nonrevascularized patients as a reference group. The previous
      revascularization strategy consisted of coronary artery bypass grafting (CABG,
      45.2%), percutaneous coronary intervention (PCI, 42.1%), or both (CABG+PCI,
      12.8%). Patients who had undergone both CABG+PCI and CABG-only had a greater
      adverse outcome risk (adjusted hazard ratio 1.27% and 1.20%, 95% confidence
      interval 1.06 to 1.53 and 1.07 to 1.35, respectively). The risk was similar for
      PCI-only patients (adjusted hazard ratio 1.04, 95% confidence interval 0.92 to
      1.19). The relations between the adjusted hazard ratio and on-treatment BP
      appeared J-shaped for each revascularization strategy, accentuated for PCI and
      diastolic BP (DBP), but excepting CABG only and DBP for which the relation was
      linear and positive. In conclusion, major adverse outcomes were more frequent in
      patients with coronary artery disease who had undergone previous CABG, with or
      without PCI, compared to those with previous PCI only. This likely reflected more
      severe vascular disease. The relation to systolic BP was J-shaped for each
      strategy. Among those patients with previous CABG only, the linear relation with
      DBP suggested that more complete revascularization might attenuate hypoperfusion
      at a low DBP. The management of BP might, therefore, require modification of
      targets according to the revascularization strategy to improve outcomes.

PMID- 20691308
TI  - Three-year outcomes following sirolimus- versus paclitaxel-eluting stent
      implantation in an unselected population with coronary artery disease (from the
      REWARDS Registry).
AB  - The Registry Experience at the Washington Hospital Center with Drug-Eluting
      Stents (REWARDS) study includes unselected patients with coronary artery disease
      treated with sirolimus-eluting stents (SESs; n = 2,392) or paclitaxel-eluting
      stents (PES; n = 1,119). This study aimed to examine the long-term safety profile
      of the 2 stents in a "real-world" population, especially in relation to stent
      thrombosis, and to compare differences in the diabetic cohort. Patients were
      followed for 3 years with regard to major adverse cardiac events (MACEs),
      including death, Q-wave myocardial infarction, and target lesion
      revascularization. Rates of stent thrombosis were also studied. Baseline
      characteristics were similar between stents. Although MACE rates at 3 years were
      similar (SES 28.1% vs PES 28.9%, p = 0.62), there was a significant difference in
      unadjusted rates of target lesion revascularization (SES 15.6% vs PES 12.6%, p =
      0.03), death (SES 15.7% vs PES 19.0%, p = 0.02), and Q-wave myocardial infarction
      (SES 0.8% vs PES 2.1%, p = 0.003). After multivariable Cox regression to adjust
      for confounders, there was no significant difference in overall MACEs. Incidence
      of stent thrombosis was higher in the SES group (SES 2.2% vs PES 1.6%, p = 0.22),
      but this was not statistically significant (hazard ratio 1.6, 95% confidence
      interval 0.8 to 2.9, p = 0.17). Overall, diabetics had a higher MACE rate, but
      there was no difference between insulin- and noninsulin-dependent diabetics. In
      conclusion, at 3 years, PES and SES achieved similar results in MACEs and stent
      thrombosis. This should foster confidence that SES or PES can be compared to
      second-generation drug-eluting stents without concerns for safety or efficacy.

PMID- 20691309
TI  - Long-term results (three-year) of emergency coronary artery bypass grafting for
      patients with unstable angina pectoris.
AB  - Satisfactory results are achieved by elective coronary artery bypass grafting
      (CABG), but the results of emergency CABG are less than satisfactory and
      readmission for cardiac events is common. We examined long-term results of
      emergency CABG for unstable angina pectoris from the viewpoints of preoperative,
      intraoperative, and postoperative factors. Subjects were 154 patients who
      underwent emergency CABG for unstable angina pectoris. Operative mortality rate
      was 1.9%. Univariate analysis showed female gender, chronic renal failure,
      hemodialysis, nonuse of human atrial natriuretic peptide (hANP), nonuse of
      angiotensin II receptor blockers and aldosterone blockers, 3-month postoperative
      brain natriuretic peptide level > or =200 pg/ml, and 3-month postoperative
      aldosterone level > or =100 pg/ml as risk factors for late cardiac events.
      Multivariate analysis confirmed nonuse of hANP, nonuse of aldosterone blockers, 3
      month brain natriuretic peptide level > or =200 pg/ml, and 3-month aldosterone
      level > or =100 pg/ml as risk factors. Intraoperative hANP infusion and
      postoperative treatment with aldosterone blockers and angiotensin II receptor
      blockers can control the renin-angiotensin-aldosterone system, inhibit left
      ventricular remodeling, decrease extent of infarction, and improve cardiac
      function, yielding a favorable long-term prognosis. The best results are obtained
      by combining good surgical technique and perioperative management with the long
      term outcome in mind.

PMID- 20691310
TI  - Meta-analysis of folic acid supplementation trials on risk of cardiovascular
      disease and risk interaction with baseline homocysteine levels.
AB  - Experimental models and observational studies suggest that homocysteine-lowering
      therapy with folic acid (FA) may prevent cardiovascular disease (CVD). However,
      FA also stimulates cell proliferation and might promote progression of
      atherosclerosis. Our objectives were to perform a meta-analysis of FA
      supplementation trials on CVD events and to explore a potential interaction
      between FA supplementation and baseline homocysteine levels on CVD events. We
      searched MEDLINE for randomized controlled trials of FA supplementation to
      prevent CVD events (January 1966 to July 2009) and performed meta-analyses using
      random effects models. For trials that reported responses to FA supplementation
      stratified by baseline levels of homocysteine, we pooled within-trial estimates
      of differences in log-relative risks by baseline homocysteine levels using a
      random effects model. Overall, FA supplementation did not affect primary
      cardiovascular clinical end points (relative risk 1.02, 95% confidence interval
      [CI] 0.93 to 1.13, p = 0.66) or stroke (relative risk 0.95, 95% CI 0.84 to 1.08,
      p = 0.43). However, in trials that reported analyses stratified by baseline
      homocysteine, effect of FA supplementation differed by strata of baseline
      homocysteine (p for interaction = 0.030). Specifically, risks of primary clinical
      CVD events comparing FA supplementation to control were 1.06 (95% CI 1.00 to
      1.13) in strata with mean baseline homocysteine levels >12 mumol/L and 0.94 (95%
      CI 0.86 to 1.03) in strata with baseline homocysteine levels <12 micromol/L. In
      conclusion, FA had no effect on CVD or stroke. However, analysis of within-trial
      results stratified by baseline homocysteine suggests potential harm in those with
      high homocysteine at baseline. This interaction may have important implications
      for recommendations of FA supplement use. In the meantime, FA supplementation
      should not be recommended as a means to prevent or treat CVD or stroke.

PMID- 20691311
TI  - Characterization of atrial remodeling studied remote from episodes of typical
      atrial flutter.
AB  - Atrial electrical remodeling has been shown after termination of atrial flutter
      (AFL); however, whether abnormalities persist beyond an arrhythmic episode is not
      known. We aimed to characterize the atrial substrate, remote from arrhythmia, in
      patients with typical AFL. We compared 20 patients, studied remote from episodes
      of typical AFL and without a history of atrial fibrillation, to 20 reference
      patients. Multipolar catheters placed at the lateral right atrium (RA), coronary
      sinus, crista terminalis, and septal RA measured the effective refractory period
      at 5 sites; conduction characteristics at the crista terminalis; and the
      conduction time along the lateral RA and coronary sinus. Electroanatomic right
      atrial maps were created to determine regional differences in voltage and
      conduction. Patients with AFL demonstrated the following compared to the
      reference patients: a larger right atrial volume (121 +/- 30 vs 83 +/- 24 ml, p =
      0.005); a prolonged P-wave duration (122 +/- 18 vs 102 +/- 11 ms, p = 0.007); a
      longer right atrial activation time (107 +/- 23 vs 85 +/- 14 ms, p = 0.02); a
      prolonged conduction time along the lateral RA (67 +/- 4 vs 47 +/- 3 ms, p
      <0.001); a slower mean conduction velocity (1.2 +/- 0.2 vs 2.1 +/- 0.6 mm/ms, p
      <0.001); a greater proportion of fractionated electrographic findings (16 +/- 4%
      vs 10 +/- 6%, p = 0.006); more frequent abnormal electrographic findings at the
      crista terminalis (4.1 +/- 2.6 vs 1.0 +/- 1.1, p = 0.001); a prolonged corrected
      sinus node recovery time (318 +/- 71 vs 203 +/- 94 ms, p = 0.02); a trend toward
      greater effective refractory period (232 +/- 29 vs 213 +/- 12 ms, p = 0.06); and
      a lower voltage (2.1 +/- 0.5 vs 3.0 +/- 0.5 mV, p <0.001). In conclusion, studied
      remote from arrhythmia, patients with AFL demonstrated significant and diffuse
      atrial abnormalities characterized by structural changes, conduction
      abnormalities, and sinus node dysfunction. These persisting abnormalities
      characterize the substrate underlying typical AFL and may account for the
      subsequent development of atrial fibrillation.

PMID- 20691312
TI  - Usefulness of CHADS2 score to predict C-reactive protein, left atrial blood
      stasis, and prognosis in patients with nonrheumatic atrial fibrillation.
AB  - The CHADS2 score (congestive heart failure, hypertension, age >75 years,
      diabetes, and previous stroke/transient ischemic attack) is used for embolic risk
      stratification in patients with atrial fibrillation (AF). Although systemic
      inflammation is a known predictor of left atrial thrombus formation in patients
      with nonrheumatic AF, the relation between the CHADS2 score and systemic
      inflammation is unknown. A total of 165 patients with nonrheumatic AF were
      enrolled and analyzed. According to the CHADS2 score, the study patients were
      grouped into low- (score 0 to 1), intermediate- (score 2 to 3), or high- (score 4
      to 6) risk categories. The plasma C-reactive protein levels, transesophageal
      echocardiographic findings, and cardiovascular events (death, stroke, and heart
      failure) were compared. Patients in the high-risk group had significantly greater
      C-reactive protein levels than those in the intermediate- and low-risk groups
      (0.80 mg/dl, range 0.21 to 1.50, vs 0.16 mg/dl, range 0.06 to 0.50, vs 0.08
      mg/dl, range 0.04 to 0.21, p <0.01). Using transesophageal echocardiography, the
      incidence of left atrial spontaneous echo contrast and left atrial thrombus
      increased with an increasing CHADS2 score. During the follow-up period, the
      cardiovascular event-free survival was significantly lower in the high-risk group
      than in the intermediate- or low-risk groups. In conclusion, in patients with
      nonrheumatic AF, CHADS2 score is related to systemic inflammation, left atrial
      thrombus formation, and prognosis.

PMID- 20691313
TI  - Detection and quantification by deformation imaging of the functional impact of
      septal compared to free wall preexcitation in the Wolff-Parkinson-White syndrome.
AB  - Pacing experiments in healthy animal hearts have suggested a larger detrimental
      effect of septal compared to free wall preexcitation. We investigated the
      intrinsic relation among the site of electrical preexcitation, mechanical
      dyssynchrony, and dysfunction in human patients. In 33 patients with Wolff
      Parkinson-White (WPW) syndrome and 18 controls, regional myocardial deformation
      was assessed by speckle tracking mapping (ST-Map) to assess the preexcitation
      site, shortening sequences and dyssynchrony, and the extent of local and global
      ejecting shortening. The ST-Map data in patients with accessory atrioventricular
      pathways correctly diagnosed as located in the interventricular septum (IVS) (n =
      11) or left ventricular free wall (LFW) (n = 12) were compared to the
      corresponding control values. A local ejecting shortening of <2 SD of the control
      values identified hypokinetic segments. The localization of the atrioventricular
      pathways by ST-Map matched with the invasive electrophysiology findings in 23 of
      33 patients and was one segment different in 5 of 33 patients. In both WPW-IVS
      and WPW-LFW, local ejecting shortening was impaired at the preexcitation site (p
      <0.01). However, at similar electrical and mechanical dyssynchrony, WPW-IVS had
      more extensive hypokinesia than did WPW-LFW (3.6 +/- 0.9 vs 1.8 +/- 1.3 segments,
      p <0.01). Compared to controls, the left ventricular function was significantly
      reduced only in WPW-IVS (global ejecting shortening 17 +/- 2% vs 19 +/- 2%, p =
      0.01; ejection fraction 55 +/- 5% vs 59 +/- 3%, p = 0.02). In conclusion,
      preexcitation is associated with local hypokinesia, which at comparable
      preexcitation is more extensive in WPW-IVS than in WPW-LFW and could adversely
      affect ventricular function. ST-Map might have a future role in detecting and
      guiding treatment of septal pathways with significant mechanical effects.

PMID- 20691314
TI  - Atrial arrhythmias in adult patients with right- versus left-sided congenital
      heart disease anomalies.
AB  - Atrial arrhythmias (AAs) are a common complication in adult patients with
      congenital heart disease. We sought to compare the lifetime prevalence of AAs in
      patients with right- versus left-sided congenital cardiac lesions and their
      effect on the prognosis. A congenital heart disease diagnosis was assigned using
      the International Disease Classification, Ninth Revision, diagnostic codes in the
      administrative databases of Quebec, from 1983 to 2005. Patients with AAs were
      those diagnosed with an International Disease Classification, Ninth Revision,
      code for atrial fibrillation or intra-atrial reentry tachycardia. To ensure that
      the diagnosis of AA was new, a washout period of 5 years after entry into the
      database was used, a period during which the patient could not have received an
      International Disease Classification, Ninth Revision, code for AA. The cumulative
      lifetime risk of AA was estimated using the Practical Incidence Estimators
      method. The hazard ratios (HRs) for mortality, morbidity, and cardiac
      interventions were compared between those with right- and left-sided lesions
      after adjustment for age, gender, disease severity, and cardiac risk factors. In
      a population of 71,467 patients, 7,756 adults developed AAs (isolated right
      sided, 2,229; isolated left-sided, 1,725). The lifetime risk of developing AAs
      was significantly greater in patients with right- sided than in patients with
      left-sided lesions (61.0% vs 55.4%, p <0.001). The HR for mortality and the
      development of stroke or heart failure was similar in both groups (HR 0.96, 95%
      confidence interval [CI] 0.86 to 1.09; HR 0.94, 95% CI 0.80 to 1.09; and HR 1.10,
      95% CI 0.98 to 1.23, respectively). However, the rates of cardiac catheterization
      (HR 0.63, 95% CI 0.55 to 0.72), cardiac surgery (HR 0.40, 95% CI 0.36 to 0.45),
      and arrhythmia surgery (HR 0.77, 95% CI 0.6 to 0.98) were significantly less for
      patients with right-sided lesions. In conclusion, patients with right-sided
      lesions had a greater lifetime burden of AAs. However, their morbidity and
      mortality were no less than those with left-sided lesions, although the rate of
      intervention was substantially different.

PMID- 20691315
TI  - Meta-analysis of pulmonary valve replacement after operative repair of tetralogy
      of fallot.
AB  - The present meta-analysis aimed to determine the outcomes and effect on right
      ventricular (RV) function of surgical pulmonary valve replacement (PVR) in
      patients after repair of tetralogy of Fallot. The reported outcomes of surgical
      PVR in children and adults after tetralogy of Fallot repair were from relatively
      small observational studies. The PubMed database was searched from its inception
      to April 2009. Observational studies reporting on the following outcomes measures
      after surgical PVR were reviewed: early and late all-cause mortalities, the redo
      PVR rate, and changes in the indexed RV volumes, ejection fraction, and QRS
      duration after PVR. Of the 305 citations screened, 15 met the criteria and were
      analyzed. The pooled early mortality rate (n = 595) was 2.1% (95% confidence
      interval [CI] 1.1% to 4.0%). The late mortality rate was 0.5%/patient-year (95%
      CI 0.2% to 0.8%/patient-year), and the redo-PVR rate was 1.9%/patient-year (95%
      CI 1.3% to 2.5%/patient-year). Data on RV volumes and ejection fractions were
      available from 5 studies (n = 141). The pooled mean difference in the indexed RV
      end-diastolic and end-systolic volume was -63 ml/m(2) (95% CI -55 to -72) and -37
      ml/m(2) (95% CI -30 to -45), respectively. No significant changes in the pooled
      mean difference of the RV ejection fraction (95% CI -1% to 3%) or QRS duration
      (95% CI -10 to 1 ms) were observed. In conclusion, surgical PVR in patients after
      tetralogy of Fallot repair has been associated with low early and late mortality
      and significant decreases in RV volumes but no changes in the RV ejection
      fraction or QRS duration.

PMID- 20691316
TI  - Outcome in stable patients with acute pulmonary embolism who had right
      ventricular enlargement and/or elevated levels of troponin I.
AB  - Normotensive patients with acute pulmonary embolism (PE) who have increased
      troponin levels and right ventricular (RV) dysfunction are thought to be at high
      risk of death, but the level of risk is unclear. We retrospectively evaluated
      outcome in 1,273 stable patients with PE who had echocardiographic evaluations of
      RV size and/or measurement of cardiac troponin I (cTnI). In-hospital all-cause
      mortality was higher in those with RV enlargement (8.0%, 19 of 237, vs 3.3%, 22
      of 663, p = 0.003). With an increased cTnI, irrespective of RV enlargement, all
      cause mortality was 8.0% (28 of 330) versus 1.9% (15 of 835) in patients with a
      normal cTnI (p <0.0001). In patients with an increased cTnI combined with an
      enlarged right ventricle, all-cause mortality was 10.2% (12 of 118) compared to
      1.9% (8 of 421) in patients who had neither (p <0.0001). These data show that
      increased levels of cTnI and RV enlargement are associated with an adverse
      outcome in stable patients with acute PE. In conclusion, increased levels of cTnI
      in combination with RV enlargement might indicate a group who would benefit from
      intense monitoring and aggressive treatment if subsequently indicated. The
      outcomes, however, were not extreme enough to warrant routine thrombolytic
      therapy.

PMID- 20691317
TI  - Relation of serum phosphorus levels to ankle brachial pressure index (from the
      Third National Health and Nutrition Examination Survey).
AB  - Higher levels of serum phosphorus that remain within the reference range are
      associated with increased risk of cardiovascular disease (CVD). However, the
      mechanisms by which higher serum phosphorus concentrations may contribute to the
      development of CVD remain unclear. Cross-sectional association between serum
      phosphorus levels and arterial stiffness as estimated by an ankle brachial
      pressure index (ABPI) >1.3 was examined in 581 participants in the Third National
      Health and Nutrition Examination Survey. Logistic regression analysis was
      performed to evaluate whether higher serum phosphorus levels were associated with
      high ABPI, independently of several potential confounders. Of 581 participants,
      38% and 10% had a serum phosphorus levels >3.5 and >4.0 mg/dl, respectively. An
      ABPI >1.3 was present in 7.3% of participants. Higher quartiles of serum
      phosphorus levels were associated with a greater prevalence of high ABPI: 5.4%,
      3.7%, 7.8%, and 12.9% for quartiles 1 (<3.1 mg/dl), 2 (3.1 to 3.4 mg/dl), 3 (3.4
      to 3.7 mg/dl), and 4 (3.7 to 5.0 mg/dl), respectively. There was a strong,
      positive association between the highest quartile of serum phosphorus (3.7 to 5.0
      mg/dl) and high ABPI compared to the reference group (3.1 to 3.4 mg/dl) after
      adjustment for demographics, traditional CVD risk factors, kidney function, C
      reactive protein, serum calcium, and 25-hydroxyvitamin D levels (adjusted odds
      ratio 4.78, 95% confidence interval 1.73 to 13.2, p = 0.003). In conclusion,
      serum phosphorus levels, even within the reference range, are independently
      associated with high ABPI, a marker of arterial stiffness, in the US adult
      population.

PMID- 20691318
TI  - Early repolarization, left ventricular diastolic function, and left atrial size
      in professional soccer players.
AB  - Recent data have suggested a relation among long-term endurance sport practice,
      left atrial remodeling, and atrial fibrillation. We investigated the influence of
      an increased vagal tone, represented by the early repolarization (ER) pattern, on
      diastolic function and left atrial size in professional soccer players. Fifty
      four consecutive athletes underwent electrocardiography, echocardiography, and
      exercise testing as part of their preparticipation screening. Athletes were
      divided into 2 groups according to presence or absence of an ER pattern, defined
      as a ST-segment elevation at the J-point (STE) > or =0.1 mm in 2 leads. For
      linear comparisons average STE was calculated. Mean age was 24 +/- 4 years.
      Twenty-five athletes (46%) showed an ER pattern. Athletes with an ER pattern had
      a significant lower heart rate (54 +/- 9 vs 62 +/- 11 beats/min, p = 0.024), an
      increased E/e' ratio (6.1 +/- 1.2 vs 5.1 +/- 1.0, p = 0.002), and larger volumes
      of the left atrium (25.6 +/- 7.3 vs 21.8 +/- 5.0 ml/m(2), p = 0.031) compared to
      athletes without an ER pattern. There were no significant differences concerning
      maximum workload, left ventricular dimensions, and systolic function. Univariate
      regression analysis revealed significant correlations among age, STE, and left
      atrial volume. In a stepwise multivariate regression analysis age, STE and e'
      contributed independently to left atrial size (r = 0.659, p <0.001). In
      conclusion, athletes with an ER pattern had an increased E/e' ratio, reflecting a
      higher left atrial filling pressure, contributing to left atrial remodeling over
      time.

PMID- 20691319
TI  - Thoracic aortic distensibility and thoracic aortic calcium (from the Multi-Ethnic
      Study of Atherosclerosis [MESA]).
AB  - Decreased arterial distensibility is an early manifestation of adverse structural
      and functional changes within the vessel wall. Its correlation with thoracic
      aortic calcium (TAC), a marker of atherosclerosis, has not been well
      demonstrated. We tested the hypothesis that decreasing aortic compliance and
      increasing arterial stiffness would be independently associated with increased
      TAC. We included 3,540 subjects (61 +/- 10 years, 46% men) from the Multi-ethnic
      Study of Atherosclerosis who had undergone an aortic distensibility (AD)
      assessment using magnetic resonance imaging. TAC was calculated using a modified
      Agatston algorithm on noncontrast cardiac computed tomographic scans.
      Multivariate regression models were calculated for the presence of TAC. Overall,
      861 subjects (24%) had detectable TAC. Lower AD was observed among those with
      versus without TAC (2.02 +/- 1.34 vs 1.28 +/- 0.74, p <0.0001). The prevalence of
      TAC increased significantly across decreasing quartiles of AD (7%, 17%, 31%, and
      42%, p <0.0001). Using multivariate analysis, TAC was independently associated
      with AD after adjusting for age, gender, ethnicity, and other covariates. In
      conclusion, our analysis has demonstrated that increased arterial stiffness is
      associated with increased TAC, independent of ethnicity and other atherosclerotic
      risk factors.

PMID- 20691320
TI  - Differences in QRS axis measurements, classification of inferior myocardial
      infarction, and noise tolerance for 12-lead electrocardiograms acquired from
      monitoring electrode positions compared to standard locations.
AB  - We tested whether the "Lund" (LU) electrode-placement system compared to the
      Mason-Likar (M-L) electrode-placement system would produce waveforms more similar
      to those of standard electrocardiograms (ECGs) with regard to the QRS axis in the
      frontal plane and QRS changes of inferior myocardial infarction (MI). We also
      tested whether LU was more noise immune than standard, and whether the noise
      immunities of the LU and M-L systems were comparable. Four 12-lead ECGs were
      recorded in 80 patients-2 standard ECGs, 1 LU ECG, and 1 M-L ECG. Further, 6 ECGs
      were recorded for 11 patients and 9 healthy volunteers-2 standard, 2 LU, and 2 M
      L ECGs-while the subjects performed limb movements. Three electrocardiographic
      readers made blinded assessments of noise levels. QRS scores in patients with
      inferior MI differed significantly between standard and M-L ECGs but not between
      standard and LU ECGs. Few of those without QRS changes of MI received QRS scores,
      but not more often on LU ECGs than on standard ECGs, and never on M-L ECGs. QRS
      axis differences were small between standard and LU ECGs, but large between
      standard and M-L ECGs. The LU system was significantly more noise immune than the
      standard, whereas the difference in noise immunity between the M-L and LU systems
      was not significant. In conclusion, the results indicate that LU might constitute
      a uniform convention for "diagnostic" ECGs and for monitoring
      electrocardiographic applications.

PMID- 20691321
TI  - Can a statin neutralize the cardiovascular risk of unhealthy dietary choices?
AB  - The cardiovascular risk reduction associated with different statins for the
      prevention of cardiovascular disease and the cardiovascular risk increase
      associated with excess dietary intake of fat have been quantified. However, these
      relative risks have never been directly juxtaposed to determine whether an
      increase in relative risk by 1 activity could be neutralized by an opposing
      change in relative risk from a second activity. The investigators compared the
      increase in relative risk for cardiovascular disease associated with the total
      fat and trans fat content of fast foods against the relative risk decrease
      provided by daily statin consumption from a meta-analysis of statins in primary
      prevention of coronary artery disease (7 randomized controlled trials including
      42,848 patients). The risk reduction associated with the daily consumption of
      most statins, with the exception of pravastatin, is more powerful than the risk
      increase caused by the daily extra fat intake associated with a 7-oz hamburger
      (Quarter Pounder) with cheese and a small milkshake. In conclusion, statin
      therapy can neutralize the cardiovascular risk caused by harmful diet choices. In
      other spheres of human activity, individuals choosing risky pursuits
      (motorcycling, smoking, driving) are advised or compelled to use measures to
      minimize the risk (safety equipment, filters, seatbelts). Likewise, some
      individuals eat unhealthily. Routine accessibility of statins in establishments
      providing unhealthy food might be a rational modern means to offset the
      cardiovascular risk. Fast food outlets already offer free condiments to
      supplement meals. A free statin-containing accompaniment would offer
      cardiovascular benefits, opposite to the effects of equally available salt,
      sugar, and high-fat condiments. Although no substitute for systematic lifestyle
      improvements, including healthy diet, regular exercise, weight loss, and smoking
      cessation, complimentary statin packets would add, at little cost, 1 positive
      choice to a panoply of negative ones.

PMID- 20691322
TI  - What the Tortoise said to Achilles.
AB  - Practitioners and investigators often view clinical trials from very different
      perspectives-the former in terms of individuals and the latter in terms of
      groups. The following whimsical dialogue highlights the philosophical foundations
      of these contrasting perspectives and illustrates their potential impact on
      patient care and public policy. The title alludes to a piece by Lewis Carroll
      regarding Zeno's paradox, purportedly proving that the fleet-footed Achilles
      cannot outrun the plodding Tortoise in a foot race.

PMID- 20691323
TI  - The snow-shoveler's ST elevation myocardial infarction.
AB  - Heavy snowfall, cold temperatures, and low atmospheric pressure during the winter
      months have been associated with increased adverse cardiovascular events.
      However, only a few cases of the "snow shoveler's infarction" have been reported.
      The investigators describe their experience with 6 patients presenting with ST
      elevation myocardial infarctions, all within a 24-hour period during an
      unprecedented snowfall (4 of whom were shoveling snow), and provide a detailed
      review of previously reported cases of snow shoveler's infarction. Consistent
      with other reports, most patients reported here had the traditional cardiac risk
      factors of hypertension, hyperlipidemia, diabetes mellitus, tobacco use, and
      sedentary lifestyle. Unique to this case series, however, was that the 4 patients
      who had histories of coronary artery disease and previous coronary artery
      stenting all presented with subacute stent thromboses documented on coronary
      angiography performed emergently. Moreover, these patients constituted 25% of all
      subacute stent thromboses diagnosed in the cardiac catheterization laboratory in
      the preceding 12 months. In conclusion, these findings suggest that in typically
      sedentary individuals with cardiac risk factors or histories of coronary artery
      disease, snow shoveling may trigger ST elevation myocardial infarction and
      therefore should be avoided. This may be most critical in patients with histories
      of coronary stent placement, considering that these findings suggest that snow
      shoveling may precipitate subacute stent thrombosis.

PMID- 20691325
TI  - Motorized scooters: boon or bane?

PMID- 20691326
TI  - Valsartan inefficacy or ill-effects of concomitant medications!

PMID- 20691327
TI  - Limiting adverse cardiac remodeling after acute myocardial infarction by blocking
      interleukin-1.

PMID- 20691328
TI  - Testing a new cognitive behavioural treatment for obesity: A randomized
      controlled trial with three-year follow-up.
AB  - It is remarkably difficult for people with obesity to maintain a new lower weight
      following weight loss. The aim of the present study was to examine the immediate
      and longer-term effects of a new cognitive behavioural treatment that was
      explicitly designed to minimise this post-treatment weight regain. One hundred
      and fifty female participants with obesity were randomized to the new treatment,
      behaviour therapy (the leading alternative psychological treatment) or guided
      self-help (a minimal intervention). Both of the main treatments resulted in an
      average weight loss of about ten percent of initial weight whereas weight loss
      was more modest with guided self-help. The participants were subsequently
      followed-up for three years post-treatment. The great majority regained almost
      all the weight that they had lost with the new treatment being no better than the
      behavioural treatment in preventing weight regain. These findings lend further
      support to the notion that obesity is resistant to psychological methods of
      treatment, if anything other than a short-term perspective is taken. It is
      suggested that it is ethically questionable to claim that psychological
      treatments for obesity "work" in the absence of data on their longer-term
      effects.

PMID- 20691329
TI  - Overgeneralization from limited data: A commentary on Cooper et al., 2010.
AB  - This article comments on a recent paper by Cooper et al. in BRAT. Its main
      purpose is to comment on the provocative conclusion in the paper that behavioral
      research on weight loss maintenance should be abandoned. We disagree, arguing
      that the authors over generalize from their research, under crediting past
      behavioral weight loss research for its accomplishments, which are considerable.
      We briefly outline areas we believe remain exciting new research directions in
      this field.

PMID- 20691330
TI  - The humbling experience of treating obesity: Should we persist or desist?
AB  - Obesity has humbled one research group after another. Some of the field's
      brightest scientists have attempted to subdue obesity by treating it, but now,
      after decades of work, treatment gains remain small, maintenance is poor, and the
      field produces effects far below what patients want or expect. This can be
      explained by strong biological and environmental forces that oppose weight loss
      and foster regain. Attempts to improve treatment must continue, but with
      recognition that treatment is a clinical measure and will not affect prevalence
      (because treatments are too expensive to be used broadly). Policy change and
      prevention will be necessary to improve public health.

PMID- 20691331
TI  - Gynecologic oncology update 2010.

PMID- 20691332
TI  - Back to the future: Targeting molecular changes for platinum resistance reversal.

PMID- 20691333
TI  - Dietary consumption of antioxidant nutrients and risk of incident cervical
      intraepithelial neoplasia.
AB  - OBJECTIVE: Women with human papillomavirus (HPV) infections are at risk for
      developing squamous intraepithelial lesions (SIL) of the cervix; however, other
      factors are required for infections to progress to SIL. We hypothesize that
      consumption of fruits and vegetables high in antioxidant nutrients may prevent,
      in part, the development of HPV-associated SIL. METHODS: This study is a nested
      case-control study of 265 HPV-positive women (93 SIL cases and 172 cytologically
      normal controls) in the Ludwig-McGill Cohort Study, Sao Paulo, Brazil. Diet was
      assessed by a self-administered food frequency questionnaire. The association
      between food and nutrient intake of antioxidants and incident SIL was determined
      by logistic regression and multinomial regression when comparing LSIL and HSILs.
      RESULTS: Higher reported consumption of papaya was inversely associated with risk
      of SIL (p trend=0.01) and strongest for >or=1 time/week (adjusted odds ratios
      (AORs)=0.19; 95%CI, 0.08-0.49). Risk of SIL was reduced among women reporting
      consumption of oranges >or=1 time/week (AOR=0.32; 95%CI, 0.12-0.87; p
      trend=0.02). Nutrient intakes of ss-cryptoxanthin and alpha-carotene were
      marginally protective against SIL. CONCLUSIONS: Frequent consumption of fruits
      high in antioxidant nutrients appears to be associated with reduced risk of
      incident SIL among Brazilian women.

PMID- 20691334
TI  - A prospective 15-year evaluation of extensive dentin-enamel-bonded pressed
      ceramic coverages.
AB  - OBJECTIVES: The purpose of this study was to investigate the durability of
      extensive dentin-enamel-bonded posterior ceramic coverages in a 15 years follow
      up. METHODS: All extensive dentin-enamel-bonded posterior partial and complete
      all-ceramic coverages placed during the period November 1992-December 1998 were
      included. In 121 patients, 252 coverages (IPS Empress) were placed. The adhesive
      bonding to dentin and enamel was performed with three 3-step and one 2-step etch
      and rinse bonding. In 106 restorations the classic Syntac was used in combination
      with the dual-cured resin composite Variolink. The other restorations were luted
      with the chemically cured resin composite Bisfil 2B and bonded with 3-step etch
      and rinse systems, classic Gluma (37), Allbond 2 (57), Syntac (32) or the 2-step
      etch and rinse system, One step (20). The ceramics were evaluated yearly by
      modified USPHS criteria during 15 years. RESULTS: Postoperative sensitivity was
      registered in 4 patients during bite forces lasting for 2-4 weeks. Fifty-five of
      228 coverages (24.1%) failed. The mean observation period of the acceptable
      coverages was 12.6 years (range 11-15 years). The main reasons for failure were
      lost restorations (18), ceramic fracture (16), and secondary caries (11).
      Significant differences in failure rate were observed between the dentin bonding
      agents but not between the two luting agents. Ceramic coverages placed on non
      vital teeth failed in 39% and on vital teeth in 20.9% (p=0.014). Logistic
      regression indicated three significant predictors for failure of the coverages:
      gender and parafunctional habits of the patient and non-vitality of the tooth.
      SIGNIFICANCE: The technique investigated showed advantages like less destruction
      of healthy tissue, and avoiding of endodontic treatment and/or deep cervical
      placement of restoration margins to obtain retention.

PMID- 20691335
TI  - Sustainability assessment of traditional fisheries in Cau Hai lagoon (South China
      Sea).
AB  - Overfishing and progressive environmental degradation of the Vietnamese Cau Hai
      coastal lagoon appear to be threatening the ecological integrity and water
      quality of the largest estuarine complex of Southeast Asia. This study assessed
      the relationships between the density of traditional fisheries and organic matter
      sedimentary contents in Cau Hai lagoon. Data revealed that the density of stake
      traps (the most common fishing gear used in this lagoon), decreasing hydrodynamic
      energy in shallow water, causes the accumulation of a large fraction of organic
      matter refractory to degradation. The relationship between biopolymeric carbon (a
      proxy of availability of organic matter) and stake traps density fits a S-shape
      curve. The logistic equation calculated a stake traps density of 90 m of net per
      hectare, as the threshold over which maximum accumulation of organic matter
      occurs in Cau Hai. With such level of stake trap density, and assuming a
      theoretical stationary status of the lagoon, the time necessary for the system to
      reach hypoxic conditions has been calculated to be circa three weeks. We
      recommend that this density threshold should not be exceeded in the Cau Hai
      lagoon and that further analyses of organic loads in the sediment should be
      conducted to monitor the trophic conditions of this highly eutrophicated lagoon.

PMID- 20691336
TI  - Nutrient availability modifies species abundance and community structure of Fucus
      associated littoral benthic fauna.
AB  - The brown alga Fucus vesiculosus is a foundation species in the Baltic Sea
      littoral, hosting a rich faunal community. We compared the species composition
      and diversity of invertebrate macrofauna living on F. vesiculosus between sites
      differing in their eutrophication status and exposure to waves at three different
      times during a season. We determined the size, nitrogen and phlorotannin content
      of the alga. The invertebrate community differed substantially between sites near
      fish farms and those in more pristine environment. Snails and bivalves were more
      abundant on the Fucus stands near fish farms than on control stands, where
      crustaceans were more abundant. The abundance of molluscs decreased with the
      increasing shore exposure, while gammaridean amphipods dominated on the exposed
      shores. Abundance of several taxa increased during the proceeding growing season.
      The density of the most important herbivore of F. vesiculosus, Idotea balthica,
      varied 100-fold during the season being the lowest in June and the highest in
      August when the generation born in the summer started to feed on Fucus. Thus, the
      diversity and composition of Fucus-associated invertebrate fauna varies both with
      environmental conditions of the stand and seasonally. Although the negative
      effects of eutrophication on distribution and abundance of Fucus stands are well
      documented, a moderate increase of nutrients was found to increase the species
      richness of Fucus-associated fauna in early summer.

PMID- 20691337
TI  - Therapeutic effects of cantharidin analogues without bridging ether oxygen on
      human hepatocellular carcinoma cells.
AB  - Previous research indicates that cantharidin, norcantharidin and their analogues
      exhibit anticancer activity due to their inhibition of cancer cell lines such as
      HL60, HT29 and L1210. The anticancer activities of cantharidin, norcantharidin
      and their analogues involve the suppression of serine/threonine protein
      phosphatases (PPs) activity. However, cantharidin is not suitable for cancer
      therapy because of its high cytotoxicity in vitro (IC(50) = 21 microM in primary
      cultured rat hepatocytes). In this study, synthetic cantharidin analogues with a
      structure of aminothiazole compounds 3-9 and a structure of anhydride compounds
      10-12 were screened for anticancer activities and cytotoxic effects on human
      hepatocellular carcinoma cell (HCC) lines HepG2, Sk-Hep1, and primary cultured
      rat hepatocytes. Experimental results indicated that compounds 3-9 did not
      perform as expected with regard to anticancer activity and exhibited lower
      cytotoxicity. Compound 10 promoted apoptosis in HepG2 (IC(50) = 62 microM) and SK
      Hep1(IC(50) = 151 microM) cell lines. Compounds 11 and 12 had anticancer
      potential similar to that of compound 10. After treatment with compounds 3-12,
      primary cultured rat hepatocytes exhibited no cytotoxicity (IC(50) > 200 microM).
      By investigating the structure-activity relationship (SAR) of these analogues as
      a whole, this study suggests that the anhydride ether oxygen such as in
      cantharidin, norcantharidin and compounds 10-12 may be correlated with HCC
      survival suppression. The results further suggest that the elimination of
      bridging ether oxygen on the ring, such as in compounds 10-12, can decrease
      cytotoxicity.

PMID- 20691338
TI  - Design, synthesis and biological evaluation of new (E)- and (Z)-1,2,3-triaryl-2
      propen-1-ones as selective COX-2 inhibitors.
AB  - A group of (E)-and (Z)-1,2,3-triaryl-2-propen-1-one derivatives possessing a
      methylsulfonyl COX-2 pharmacophore at the para position of the C-1 phenyl ring
      were synthesized and evaluated as selective COX-2 inhibitors. In vitro COX-1/COX
      2 structure-activity relationships were determined by varying the substituents on
      the C-3 propenone moiety. Among the 1,2,3-triaryl-2-propen-1-ones, (Z)-1-(4
      (methylsulfonyl)phenyl)-2,3-diphenylprop-2-en-1-one (3b) showed the most potency
      and selectivity on COX-2 inhibition (COX-2 IC(50) = 0.07 microM; selectivity
      index = 201). The Z-propenones were also found to be more potent and selective
      than their E-isomers for COX-2 inhibitory activity. The structure-activity data
      acquired indicate that the geometry of propenone and also the type of
      substituents on the C-3 propenone are important for COX-2 inhibitory activity.

PMID- 20691339
TI  - Synthesis of substituted thieno[2,3-d]pyrimidine-2,4-dithiones and their S
      glycoside analogues as potential antiviral and antibacterial agents.
AB  - Previously, we synthesized and evaluated several thienopyrimidine derivatives
      containing heterocyclic ring substituents linked to the pyrimidine-2-thione
      nucleus at C-2 by a two- to four-atom spacer as potential anti-HIV-1 and
      antimicrobial agents. Also, from the literature, S-substituted pyrimidin-4-ones A
      and B exhibited interesting anti-HIV-1 activity. To further investigate the
      synthesis, tools and biological activities, we synthesized several new
      thienopyrimidine derivatives derived from thieno[2,3-d]-pyrimidine-2,4-dithione
      (3a,b) The compounds were designed to comprise the heterocyclic substituents
      directly linked to the thienopyrimidines nucleus at C-2. Moreover, various
      related triazolo[4,3-a]benzothieno[2,3-d]pyrimidines derived from 2
      thioxothienopyrimidine were also prepared as isosteres. Among the synthesized
      derivatives 3-18, the compounds 3a, 8a, 10a, 13a and 14a were showing complete
      inhibition at 128 mg/mL or less.

PMID- 20691341
TI  - Is the education worth the debt?

PMID- 20691342
TI  - Teaching orthodontic residents and clinicians about cleft palate treatment.

PMID- 20691344
TI  - Dehiscence and fenestration in patients with Class I and Class II Division 1
      malocclusion assessed with cone-beam computed tomography.
AB  - INTRODUCTION: The aim of this study was to compare the presence of alveolar
      defects (dehiscence and fenestration) in patients with Class I and Class II
      Division 1 malocclusions and different facial types. METHODS: Seventy-nine Class
      I and 80 Class II patients with no previous orthodontic treatment were evaluated
      using cone-beam computed tomography. The sample included 4319 teeth. All teeth
      were analyzed by 2 examiners who evaluated sectional images in axial and cross
      sectional views to check for the presence or absence of dehiscence and
      fenestration on the buccal and lingual surfaces. RESULTS: Dehiscence was
      associated with 51.09% of all teeth, and fenestration with 36.51%. The Class I
      malocclusion patients had a greater prevalence of dehiscence: 35% higher than
      those with Class II Division 1 malocclusion (P <0.01). There was no statistically
      significant difference between the facial types. CONCLUSIONS: Alveolar defects
      are a common finding before orthodontic treatment, especially in Class I
      patients, but they are not related to the facial types.

PMID- 20691346
TI  - Orthodontic treatment-related white spot lesions: a 14-year prospective
      quantitative follow-up, including bonding material assessment.
AB  - INTRODUCTION: White spots (WS) related to orthodontic treatment are severe
      cariologic and cosmetic complications, but they are shown to be partially reduced
      by remineralization or abrasion in short-term follow-ups. In this prospective
      study, we quantitatively analyzed changes in WS in general and in treatment
      related white spot lesions (WSL) during orthodontic treatment and at a 12-year
      follow-up after treatment. In addition, we quantitatively compared the effects of
      an acrylic bonding material vs a glass ionomer cement (GIC) on WSL. METHODS: Sum
      areas of WS and WSL were calculated on scans of standardized photos of the
      vestibular surfaces of 4 teeth in consecutive orthodontic patients (median
      treatment time, 1.7 years) bonded with the 2 materials in a split-mouth design.
      Comparisons were made in 59 patients before treatment (BF), at debonding (T0), at
      1 year (T1), and at 2 years (T2), and in 30 patients at a 12-year follow-up (T3)
      with the Friedman test followed by pairwise comparisons with the Wilcoxon matched
      pairs signed rank test. Differences of the effects of acrylic vs GIC on the sum
      areas of WSL were tested for each observation period with the Mann-Whitney U
      test. RESULTS: Increases in the sum areas of WS and WSL from BF to T0 (P <0.001)
      were followed by significant decreases at T1 (P <0.001) and T2 (P <0.01 for WS; P
      <0.001 for WSL). Significant changes were also found in the sum areas for WS at
      T3 compared with T2 (P <0.01), but not for WSL (P = 0.328). The sum areas of WS
      and WSL at T3 did not return to BF levels (P <0.001). Sum areas of WSL were
      higher for surfaces bonded with acrylic compared with GIC for each observation
      period from BF to T2 (P >0.001), and from T2 to T3 (P >0.05). CONCLUSIONS:
      Although significantly reduced during the 12-year follow-up and significantly
      lower with the GIC than the acrylic material at bonding, WSL are a cariologic and
      cosmetic problem for many orthodontic patients.

PMID- 20691348
TI  - Efficiency of self-ligating vs conventionally ligated brackets during initial
      alignment.
AB  - INTRODUCTION: The aim of this study was to compare the efficiency of self
      ligating (SL) and conventionally ligated (CL) brackets during the first 20 weeks
      of extraction treatment. METHODS: Study models of 50 consecutive patients who had
      premolar extractions in the maxillary and/or mandibular arch, 0.022 x 0.028-in
      slot brackets, and similar archwire sequences were examined. Forty-four arches
      received SL Damon 3MX brackets (Ormco, Glendora, Calif), and 40 arches received
      either CL Victory Series (3M Unitek, Monrovia, Calif) or Mini-Diamond (Ormco)
      brackets. The models were evaluated for anterior arch alignment, extraction
      spaces, and arch dimensions at pretreatment (T0), 10 weeks (T1), and 20 weeks
      (T2). RESULTS: There were no significant differences between the SL and CL groups
      at 20 weeks in irregularity scores (mandibular arch, P = 0.54; maxillary arch, P
      = 0.81). There were no significant differences in passive extraction space
      closures between the SL and CL groups (mandibular arch, T0-T2, P = 0.85;
      maxillary arch, T0-T2, P = 0.33). Mandibular intercanine widths increased from T0
      to T2: 1.96 and 2.86 mm in the SL and CL groups, respectively. This was not
      significant between the groups (P = 0.31). Logistic regression did not show a
      difference between the SL and CL bracket groups. CONCLUSIONS: SL brackets were no
      more efficient than CL brackets in anterior alignment or passive extraction space
      closure during the first 20 weeks of treatment. Ligation technique is only one of
      many factors that can influence the efficiency of treatment. Similar changes in
      arch dimensions occurred, irrespective of bracket type, that might be attributed
      to the archform of the archwires.

PMID- 20691352
TI  - Force characteristics of nickel-titanium open-coil springs.
AB  - INTRODUCTION: The objective of this study was to quantify the properties of
      commercially available nickel-titanium open-coil springs. METHODS: Eleven springs
      from 3 manufacturers were tested 5 times over a 12-week period. A universal
      testing machine was used to measure the force generated when open-coil springs
      were compressed to half of their original length and then gradually allowed to
      decompress. RESULTS: The average forces generated at the initial recording
      session for uniformly wound springs from GAC International (Bohemia, NY) and 3M
      Unitek (Monrovia, Calif) were 19.3% to 42.7% and 9.7% to 38.8% below the
      manufacturers' labeled force levels, respectively. GAC's 100-, 150-, and 200-g
      stop-wound coils demonstrated statistically and clinically significant stepwise
      force degradation over the 12-week experimental period (P <0.0001). GAC's
      uniformly wound light (100 g) coils generated the lowest load-deflection ratios
      (23.7 g/mm). CONCLUSIONS: Open coils might need to be compressed by more than one
      third of their original length to produce the labeled forces. Uniformly wound
      coils generally produce lower load-deflection ratios and maximum forces, which
      are generally more acceptable for tooth movement.

PMID- 20691350
TI  - Cherubism gene Sh3bp2 is important for optimal bone formation, osteoblast
      differentiation, and function.
AB  - INTRODUCTION: Cherubism is a human genetic disorder that causes bilateral
      symmetrical enlargement of the maxilla and the mandible in children. It is caused
      by mutations in SH3BP2. The exact pathogenesis of the disorder is an area of
      active research. Sh3bp2 knock-in mice were developed by introducing a Pro416Arg
      mutation (Pro418Arg in humans) in the mouse genome. The osteoclast phenotype of
      this mouse model was recently described. METHODS: We examined the bone phenotype
      of the cherubism mouse model, the role of Sh3bp2 during bone formation,
      osteoblast differentiation, and osteoblast function. RESULTS: We observed delays
      in early postnatal development of homozygous Sh3bp2(KI/KI) mice, which exhibited
      increased growth plate thickness and significantly decreased trabecular bone
      thickness and bone mineral density. Histomorphometric and microcomputed
      tomography analyses showed bone loss in the cranial and appendicular skeletons.
      Sh3bp2(KI/KI) mice also exhibited a significant decrease in osteoid formation
      that indicated a defect in osteoblast function. Calvarial osteoblast cell
      cultures had decreased alkaline phosphatase expression and mineralization,
      suggesting reduced differentiation potential. Gene expression of osteoblast
      differentiation markers such as collagen type I, alkaline phosphatase, and
      osteocalcin were decreased in osteoblast cultures from Sh3bp2(KI/KI) mice.
      CONCLUSIONS: These data suggest that Sh3bp2 regulates bone homeostasis through
      not only osteoclast-specific effects, but also through effects on osteoblast
      differentiation and function.

PMID- 20691354
TI  - Comparison of Twin-block and Dynamax appliances for the treatment of Class II
      malocclusion in adolescents: a randomized controlled trial.
AB  - INTRODUCTION: The aim of this study was to compare the effectiveness of Twin
      block and Dynamax appliances for the treatment of Class II Division 1
      malocclusion. METHODS: This was a randomized controlled trial involving 32 boys
      and 32 girls aged 10 to 14 years with Class II Division 1 malocclusion. They were
      randomly allocated to either the Dynamax appliance group or the Twin-block
      appliance group. Treatment was provided by 4 clinicians at 2 centers. Records
      were taken at the start and the end of the functional phase and after all
      treatment. In addition, incisal overjet, the number of appliance breakages, and
      adverse events or side effects of the treatment were recorded at each patient
      visit. RESULTS: The data monitoring committee in an interim analysis at 18 months
      after the start of the trial found significantly greater overjet reduction in the
      Twin-block group than in the Dynamax group and more breakages and adverse events
      with the Dynamax appliance. As a result, treatment with the Dynamax appliance was
      terminated, and those patients completed treatment with the Twin-block or a fixed
      appliance. Regression analysis showed a statistically significant difference in
      the performance over time between the Twin-block and Dynamax appliances in terms
      of reduction in overjet, with the Twin-block appliance performing significantly
      better than the Dynamax. The incidence of adverse events was greater in the
      Dynamax group (82%) than in the Twin-block group (16%), with a statistically
      significant difference (P <0.001) between the 2 groups. CONCLUSIONS: The Twin
      block appliance was more effective than the Dynamax appliance when overjet was
      evaluated and the Dynamax appliance patients reported greater incidence of
      adverse events with their appliance than those who were treated with the Twin
      block appliance.

PMID- 20691355
TI  - Occlusal stability of adult Class II Division 1 treatment with the Herbst
      appliance.
AB  - INTRODUCTION: During recent years, some articles have been published on Herbst
      appliance treatment in adult patients, an approach that has been shown to be most
      effective in Class II treatment in both early and late adulthood. However, no
      results on stability have yet been published. Our objective was to analyze the
      short-term occlusal stability of Herbst therapy in adults with Class II Division
      1 malocclusions. METHODS: The subjects comprised 26 adults with Class II Division
      1 malocclusions exhibiting a Class II molar relationship > or =0.5 cusp
      bilaterally or > or =1.0 cusp unilaterally and an overjet of > or =4.0 mm. The
      average treatment time was 8.8 months (Herbst phase) plus 14.7 months (subsequent
      multi-bracket phase). Study casts from before and after treatment and after an
      average retention period of 32 months were analyzed. RESULTS: After retention,
      molar relationships were stable in 77.6% and canine relationships in 71.2% of the
      teeth. True relapses were found in 8.2% (molar relationships) and 1.9% (canine
      relationships) of the teeth. Overjet was stable in 92.3% and overbite in 96.0% of
      the patients; true relapse did not occur. CONCLUSIONS: Herbst treatment showed
      good occlusal stability 2.5 years after treatment in adults with Class II
      Division 1 malocclusions.

PMID- 20691356
TI  - Oral health-related quality of life and orthodontic treatment seeking.
AB  - INTRODUCTION: The aim of this study was to assess oral health-related quality of
      life (OHQOL) in adolescents who sought orthodontic treatment. A comparison
      between these adolescents and their age-matched peers who were not seeking
      orthodontic treatment provided an assessment of the role of OHQOL in treatment
      seeking. METHODS: The sample consisted of 225 subjects, 12 to 15 years of age;
      101 had sought orthodontic treatment at a university clinic (orthodontic group),
      and 124, from a nearby public school, had never undergone or sought orthodontic
      treatment (comparison group). OHQOL was assessed with the Brazilian version of
      the short form of the oral health impact profile, and malocclusion severity was
      assessed with the index of orthodontic treatment need. RESULTS: Simple and
      multiple logistic regression analysis showed that those who sought orthodontic
      treatment reported worse OHQOL than did the subjects in the comparison group (P
      <0.001). They also had more severe malocclusions as shown by the index of
      orthodontic treatment need (P = 0.003) and greater esthetic impairment, both when
      analyzed professionally (P = 0.008) and by self-perception (P <0.0001). No sex
      differences were observed in quality of life impacts (P = 0.22). However, when
      the orthodontic group was separately evaluated, the girls reported significantly
      worse impacts (P = 0.05). After controlling for confounding (dental caries
      status, esthetic impairment, and malocclusion severity), those who sought
      orthodontic treatment were 3.1 times more likely to have worse OHQOL than those
      in the comparison group. CONCLUSIONS: Adolescents who sought orthodontic
      treatment had more severe malocclusions and esthetic impairments, and had worse
      OHQOL than those who did not seek orthodontic treatment, even though severely
      compromised esthetics was a better predictor of worse OHQOL than seeking
      orthodontic treatment.

PMID- 20691357
TI  - Evaluation of the effects of malocclusion and orthodontic treatment on self
      esteem in an adolescent population.
AB  - INTRODUCTION: The purpose of this study was to evaluate the effects of
      malocclusion and orthodontic treatment on adolescent self-esteem. METHODS: A
      total of 4509 middle school students were clinically evaluated for dental
      crowding. Lip protrusion was also measured with a specially designed ruler.
      Rosenberg's self-esteem scale was used to determine each subject's level of self
      esteem. RESULTS: The results showed that sex played a role in the relationship
      between self-esteem and malocclusion. For the girls, crowding of the anterior
      teeth had significant effects on their self-esteem; however, there was no
      significant difference in the boys' self-esteem. After fixed orthodontic
      treatment, the girls had higher self-esteem than the untreated malocclusion
      group. Girls with an ideal profile and good tooth alignment also showed higher
      self-esteem than students with crowding or protrusion. CONCLUSIONS: This clinical
      study proved that malocclusion and fixed orthodontic treatment can affect self
      esteem in adolescent girls.

PMID- 20691358
TI  - Facial soft-tissue changes in skeletal Class III orthognathic surgery patients
      analyzed with 3-dimensional laser scanning.
AB  - INTRODUCTION: Patients undergoing orthognathic surgery show considerable changes
      in both hard and soft tissues. The purpose of this study was to use a 3
      dimensional (3D) laser scanner to evaluate the soft-tissue changes after the
      correction of skeletal Class III malocclusions with orthognathic surgery.
      METHODS: The subjects consisted of 20 Korean patients with skeletal Class III
      malocclusion who underwent LeFort I osteotomy with maxillary advancement and
      posterior nasal spine impaction, along with bilateral intraoral vertical ramus
      osteotomy for mandibular setback. Ten patients (group 1) had 2-jaw surgery with
      genioplasty, and the other 10 (group 2) had 2-jaw surgery without genioplasty.
      Three-dimensional images of the patients were acquired with a 3D laser scanner.
      The ratios of soft-tissue changes to hard-tissue movements were analyzed and
      compared between the 2 groups. In addition, the changes in the soft-tissue
      landmarks in the 3D coordinates and the 3D linear, angular, and proportional
      changes were measured preoperatively and postoperatively, and compared. RESULTS:
      There was no significant difference between the groups in the horizontal ratios
      of the soft-tissue to hard-tissue changes. In both groups, the ratios of the
      horizontal changes in the paranasal area were higher than in the subnasal area.
      There were more changes in the subalar area than in the supracommissural area,
      and more changes in the chin and labiomental areas than in the subcommissural
      area. Ala moved anterolaterally, and cheilion moved posteroinferiorly. The
      distance between upper-lip point and cheilion increased significantly (P <0.05).
      In the 3D angles, transverse nasal prominence and transverse upper lip prominence
      increased significantly (P <0.05). CONCLUSIONS: The 3D analysis in this study can
      be used to estimate the soft-tissue changes in Class III patients who undergo
      orthognathic surgery.

PMID- 20691359
TI  - Computed tomography evaluation of mandibular incisor bony support in untreated
      patients.
AB  - INTRODUCTION: In this study, we aimed to verify, via computed volumetric
      tomography, a correlation between the morphology of the mandibular symphysis and
      the various facial types. METHODS: From a sample of 148 digital volumetric
      tomographs, the subjects were classified as either short face (25 subjects),
      normal face (27 subjects), or long face (28 subjects) according to the average
      values of their Frankfort-mandibular plane angle. The 80 healthy subjects were
      between 12 and 40 years of age. Tomography was carried out using NewTom 3G volume
      scanner (QRsr1, Verona, Italy). The following parameters were measured on the
      sections corresponding to the 4 mandibular incisors: height, thickness, and area
      of the entire symphysis; height, thickness, and area of the cancellous bone of
      the symphysis; distance of the vestibular and lingual cortices from the apices of
      the 4 incisors; and possible inclination of each mandibular incisor, expressed in
      degrees. The F test or analysis of variance (ANOVA) and the Tukey HSD Test were
      subsequently used. RESULTS: The total thickness of the symphysis was greater in
      the short-face subjects than in the long-face subjects. No statistically
      significant differences in the total and cancellous areas of the symphysis were
      found between the 3 facial types. In all 3 groups, the total and cancellous
      heights and areas were greater at the central incisors than at the lateral
      incisors. CONCLUSIONS: There is a statistically significant relationship between
      facial type and the total thickness of the mandibular symphysis.

PMID- 20691360
TI  - Risk factors for incidence and severity of white spot lesions during treatment
      with fixed orthodontic appliances.
AB  - INTRODUCTION: The development of incipient caries, or white spot lesions (WSLs),
      is a significant clinical problem in orthodontics. The purpose of this study was
      to retrospectively determine the incidence and severity of WSLs by examining
      pretreatment and posttreatment digital photographs. METHODS: A total of 332
      consecutive finished patients from a university graduate orthodontic clinic were
      evaluated. Initial and final digital images were compared to assess WSLs. The
      facial surfaces of the anterior 8 maxillary teeth were analyzed. The percentage
      area of WSL per total facial tooth surface was calculated to control for
      magnification differences. Reliability of the method was assessed by comparison
      with direct clinical examination data. Patient and operator factors, and
      treatment complexity and outcomes were evaluated as predictors of WSL incidence
      and severity. RESULTS: Agreement between direct clinical examination and digital
      photo data was excellent, with an intraclass correlation coefficient 0.88 and a
      0.3% average difference between methods. The incidence of at least 1 WSL on the
      labial surface of the anterior 8 maxillary teeth was 36%. The order of incidence
      was lateral incisor (34%), canine (31%), premolar (28%), and central incisor
      (17%). CONCLUSIONS: Risk factors for the development of incipient caries during
      orthodontic treatment were young age (preadolescent) at the start of treatment,
      number of poor hygiene citations during treatment, unfavorable clinical outcome
      score, white ethnic group, and inadequate oral hygiene at the initial
      pretreatment examination. The use of computer software to evaluate digital photos
      retrospectively is a valid method for assessing the incidence and severity of
      WSLs on the maxillary anterior incisors, canines, and premolars.

PMID- 20691361
TI  - Debonding of ceramic brackets by a new scanning laser method.
AB  - INTRODUCTION: The purpose of this in-vitro study was to develop a new method to
      debond ceramic brackets by scanning with an Er:YAG laser. METHODS: Sixty bovine
      mandibular incisors were randomly divided into 2 groups of 30. Polycrystalline
      ceramic brackets were placed on their labial surfaces by using the orthodontic
      composite adhesive Transbond XT (3M Unitek, Monrovia, Calif) and light cured for
      a total of 40 seconds. The first group was the control group, with no laser
      application performed. The Er:YAG laser was used on each bracket in the study
      group at 4.2 W for 9 seconds with the scanning method. The force required for
      debonding the brackets was applied 45 seconds after laser exposure. Shear bond
      strengths were measured in megapascals with a universal testing machine, and
      adhesive remnant index scores were assigned to each specimen. RESULTS:
      Statistically significant (P <0.001) lower shear bond strengths were found in the
      laser group (9.52 MPa) compared with the control group (20.75 MPa). Likewise, the
      adhesive remnant index scores were statistically different (P <0.001); the laser
      group had twice as many samples with adhesive, with the adhesive remnant index
      scores of 2 or 3. CONCLUSIONS: The application of the Er:YAG laser with the
      scanning method is effective for debonding ceramic brackets by degrading the
      adhesive through thermal softening.

PMID- 20691362
TI  - Effects of high-intensity curing lights on microleakage under orthodontic bands.
AB  - INTRODUCTION: Our objective was to compare the effects of 3 light-curing units
      (LCUs) (quartz-tungsten-halogen [QTH], light-emitting diode [LED], and plasma-arc
      curing [PAC]) on the microleakage patterns of a polyacid-modified composite
      (PAMC) for band cementation between the cement-enamel and the cement-band
      interfaces from the buccal, lingual, occlusal, and gingival margins. METHODS:
      Sixty freshly extracted third molars were randomly divided into 3 groups of 20
      teeth each. Microetched molar bands were cemented in all groups with the PAMC
      (Ultra Band-Lok, Reliance Orthodontic Products, Itasca, Ill) and cured for 30
      seconds with the QTH (Hilux 350, Express Dental Products, Toronto, Ontario,
      Canada), for 20 seconds with the LED (Elipar Freelight 2, 3M Espe, Seefeld,
      Germany), or for 6 seconds with the PAC (Power-Pac, American Medical
      Technologies, Hannover, Germany). A dye penetration method was used for
      microleakage evaluation. Microleakage was determined with a stereomicroscope for
      the cement-band and cement-enamel interfaces from the buccal and lingual sides at
      the occlusal and gingival margins. Statistical analyses were performed with the
      Kruskal-Wallis and Mann-Whitney U tests. The level of significance was set at P
      <0.05. RESULTS: The gingival sides in the LED and PAC groups had higher
      microleakage scores compared with those observed on the occlusal sides at both
      the cement-band and cement-enamel interfaces. The buccal sides had similar
      microleakage values compared with those on the lingual sides for the cement
      enamel and cement-band interfaces in all LCU types. Statistical comparisons
      showed that there were statistically significant differences among the
      investigated LCUs at the cement-enamel interface (P <0.05). Post hoc comparisons
      showed statistically significant microleakage differences between the PAC
      (median, 0.950 mm), the QTH (median, 0.383 mm) (P <0.01), and the PAC and the LED
      (median, 0.558 mm) (P <0.05) LCUs at the cement-enamel interfaces. CONCLUSIONS:
      The high-intensity curing device PAC is associated with more microleakage than
      the LED and QTH at the cement-enamel interface.

PMID- 20691363
TI  - Effect of early orthodontic force on shear bond strength of orthodontic brackets
      bonded with different adhesive systems.
AB  - INTRODUCTION: This study was conducted to evaluate the effect of applying early
      orthodontic force on the shear bond strength (SBS) of orthodontic brackets bonded
      with 4 adhesive systems. METHODS: Eighty stainless steel brackets were bonded to
      the enamel surfaces of extracted premolars with 4 adhesive systems. For each
      adhesive, 10 brackets were bonded without application of force (groups 1, 3, 5,
      and 7), and another 10 were subjected to a 120-g force with a coil spring (groups
      2, 4, 6, and 8). This force was applied 30 minutes after bonding and maintained
      for 24 hours. Groups 1 and 2 had Rely-a-bond primer and Rely-a-bond adhesive
      (Reliance Orthodontic Products, Itasca, Ill). Groups 3 and 4 had Transbond XT
      primer and Transbond XT adhesive (3M Unitek, Monrovia, Calif). Groups 5 and 6 had
      Transbond Plus Self Etching Primer and Transbond XT adhesive (3M Unitek). Groups
      7 and 8 had RelyX Unicem (3M ESPE, Seefeld, Germany). After thermocycling, SBS
      testing was performed by using a universal testing machine (Type 500, Lloyd
      Instruments Ltd, Fareham Hants, UK). The results of SBS testing for all adhesives
      were analyzed by 2-way analysis of variance and the Duncan test. The unpaired
      Student t test was used to compare the effect of force on the SBS of each
      adhesive. RESULTS: Transbond XT primer and its adhesive had the highest values
      (without force, 11.2 +/- 3.1 MPa; with force, 10.7 +/- 2.7 MPa), and RelyX Unicem
      had the lowest (without force, 5.8 +/- 1.5MPa; with force, 5.7 +/- 1.6 MPa).
      Application of force yielded nonsignificant reductions in SBS for all adhesives;
      this reduction was less pronounced with RelyX Unicem. CONCLUSIONS: For all
      studied adhesive systems, orthodontic force up to 120 g can be applied within the
      first hour after bonding with no deleterious effects on bond strength.

PMID- 20691364
TI  - Treatment of an ankylosed maxillary incisor by intraoral alveolar bone
      distraction osteogenesis.
AB  - An ankylosed tooth and adjacent alveolar process can lead to the development of
      an open bite, an unesthetic smile line, and abnormal function in mastication.
      Intraoral alveolar bone distraction osteogenesis is an option for treating an
      ankylosed tooth. The purpose of this clinical report was to show the treatment of
      a growing patient with an ankylosed maxillary central incisor. A simple tooth
      borne intraoral distractor was made with an expansion screw and 0.9-mm stainless
      steel wire, which enabled it to move easily. Intraoral alveolar bone distraction
      osteogenesis will give the best results in patients with favorable root length
      and severely resorbed alveolar bone in the vertical dimension.

PMID- 20691365
TI  - Class III subdivision malocclusion corrected with asymmetric intermaxillary
      elastics.
AB  - Correcting a Class III subdivision malocclusion is usually a challenge for an
      orthodontist, especially if the patient's profile does not allow for any
      extractions. One treatment option is to use asymmetric intermaxillary elastics to
      correct the unilateral anteroposterior discrepancy. However, the success of this
      method depends on the individual response of each patient and his or her
      compliance in using the elastics. The objectives of this article were to present
      a successful treatment of a Class III subdivision patient with this approach and
      to illustrate and discuss the dentoskeletal changes that contributed to the
      correction.

PMID- 20691366
TI  - Interview with an innovator: SureSmile Chief Clinical Officer Rohit C. L.
      Sachdeva.

PMID- 20691367
TI  - Heel Pain. Foreword.

PMID- 20691368
TI  - Heel pain. Preface.

PMID- 20691369
TI  - Pediatric heel pain.
AB  - Heel pain is a condition that is generally more common in the adult population.
      However, it is a condition that the foot and ankle specialist must be prepared to
      treat in pediatric patients. The insidious onset of heel pain in the pediatric
      patient can be an enigma to the foot and ankle specialist. Some of the more
      common etiologies for pediatric heel pain are discussed. The presenting signs and
      symptoms, as well as proper workup and treatment are discussed. Two case reports
      of unusual pediatric calcaneal fractures are also presented.

PMID- 20691370
TI  - Plantar fasciitis: current diagnostic modalities and treatments.
AB  - Plantar fasciitis is a common cause of heel pain. The diagnosis is made
      clinically and validated with different diagnostic modalities ranging from
      ultrasound to magnetic resonance imaging. Treatments vary from stretching
      exercises to different surgical options. No single treatment is guaranteed to
      alleviate the heel pain.

PMID- 20691371
TI  - Internal and external fixation approaches to the surgical management of calcaneal
      fractures.
AB  - Calcaneal fractures are one of the most difficult fractures to surgically manage
      and often require a steep learning curve to achieve consistent results. They
      usually occur in young individuals with labor intensive occupations and are
      associated with major complications. Conservative treatment of intraarticular
      calcaneal fractures with displacement often results in significant deformity,
      bone loss, and posttraumatic arthrosis. Optimally, an open approach is required
      in most cases to achieve anatomic reduction and successful long-term outcomes.

PMID- 20691372
TI  - Complications of heel surgery.
AB  - Surgical complications of the calcaneus are unique to that structure but do not
      have a greater incidence than in any other part of the foot or ankle. The first
      tenet of any complication, however, is to recognize it. When all is said and
      done, recognition is probably the most important step when a complication arises.

PMID- 20691373
TI  - Dermatologic causes of heel pain.
AB  - There are many causes of heel pain. Not all are characterized as plantar
      fasciitis or osseous pathology. Sometimes patients present with heel pain caused
      by a dermatologic entity. This article describes some of the most common
      pathologies.

PMID- 20691374
TI  - Management of calcaneal osteomyelitis.
AB  - Calcaneal osteomyelitis is a complicated clinical scenario, which is often very
      difficult to treat. It can occur in individuals of any age who are injured or
      immunocompromised, and once diagnosed, aggressive management should be initiated.
      Treatment ranges from antibiotics alone to radical debridement or amputation. If
      there is a delay in both diagnosis and treatment, calcaneal osteomyelitis can be
      limb threatening or even life threatening.

PMID- 20691375
TI  - Systemic causes of heel pain.
AB  - The clinical course of heel pain can be frustrating to the clinician and the
      patient. Most heel pain responds to conservative care in a short period of time.
      However, other causes should be considered, especially if the heel pain is
      recalcitrant to treatment. A detailed history and physical examination, along
      with appropriate laboratory tests and radiological studies, can direct the
      physician toward the correct diagnosis. There are many systemic causes of heel
      pain, some common and others uncommon. Regardless of the incidence, a strong
      index of suspicion is raised whenever the heel pain fails to respond as routine
      plantar fasciitis should.

PMID- 20691376
TI  - Painful prominences of the heel.
AB  - Heel pain is a common malady, with reported prevalence ranging from 4% to 21%.
      Referral to foot and ankle specialists for heel pain is also common, but patient
      awareness of the cause of heel pain may be limited. Many misconceptions about how
      heel exostoses relate to heel pain exist in the medical community and the general
      patient population, with many patients referred for or presenting with the simple
      complaint ''I have a heel spur.'' This article reviews the common exostoses of
      the heel, including plantar, lateral, and posterior spurs, with specific
      attention to the cause and treatments.

PMID- 20691377
TI  - Combined distraction osteogenesis and Papineau technique for an open fracture
      management of the distal lower extremity.
AB  - Despite modern surgical techniques and advanced antimicrobial therapy, open lower
      extremity fracture management and osteomyelitis remain a challenge for
      reconstructive surgeons. Posttraumatic composite bone and soft tissue defects are
      usually the result of high-energy trauma and are often associated with
      concomitant injuries, therefore making complex reconstruction more difficult.
      This article presents a case report of an open distal tibial fracture managed by
      a simultaneous distraction osteogenesis and Papineau technique with a long term
      follow-up and literature review.

PMID- 20691378
TI  - Recurrent acute compartment syndrome of the foot following a calcaneal fracture
      repair.
AB  - Acute compartment syndrome is a known possible complication of calcaneal
      fractures and few case reports have documented a recurrent event after initial
      surgical fasciotomies. This article describes a rare case demonstrating a
      recurrence of acute compartment syndrome within days of initial fasciotomies and
      surgical repair of a comminuted calcaneal fracture.

PMID- 20691379
TI  - Liver failure. Preface.

PMID- 20691380
TI  - Infectious diseases in end-stage liver disease patients.
AB  - Patients with chronic liver diseases sustain impairment to immune systems, which
      worsens over time. These defects in their host defense lead to risks of bacterial
      infections and increased morbidity. Providers should have heightened surveillance
      for infectious diseases and suspect one with any acute change in status. Patient
      history may reveal rare infections and allow initiation of early appropriate
      therapy. There should be a low threshold for obtaining diagnostic cultures and
      peritoneal fluid samples and discussing possible causes with an infectious
      diseases consultant or a microbiology laboratory. These maneuvers will maximize
      therapy in patients at high risk for death due to infectious disease.

PMID- 20691381
TI  - Management of ascites.
AB  - Ascites is the most common complication of cirrhosis, and it often leads to
      hospitalization. Quality of life and mortality are negatively impacted by
      ascites. This article highlights the management of this potentially deadly
      complication.

PMID- 20691382
TI  - Correction of coagulopathy in the setting of acute liver failure.
AB  - The depletion of vital coagulation factors and proteins in the setting of acute
      liver failure (ALF) is common and multifactorial. The management of critically
      ill patients with ALF is difficult and requires a multidisciplinary approach to
      effective treatment. Critical care nurses are essential in identifying potential
      sources of bleeding, monitoring for transfusion reactions, and staying vigilant
      for medication-related adverse reactions. Prevention and treatment of bleeding
      disorders is a priority because ineffective therapy can lead to hazardous
      consequences. Correction of coagulopathy for treatment of bleeding and reversal
      for invasive procedures should include a multifactorial therapeutic plan
      emphasizing the correction of all coagulation factors. The limitations of current
      knowledge in effective correction should serve as a stimulus for future research.

PMID- 20691383
TI  - Drug-induced liver disease.
AB  - More than 1000 drugs have been associated with hepatic injury, which can present
      in all forms of acute and chronic liver disease. The identification and
      prevention of drug-induced liver disease remain challenging tasks for health care
      professionals as reliable and practical assessment tools are not currently
      available to diagnose drug-induced liver disease. The management of drug-induced
      liver injury is generally supportive, and the recognition and avoidance of
      causative agents remain the most effective strategy for positive clinical
      outcomes.

PMID- 20691384
TI  - Drug dosing considerations for the critically ill patient with liver disease.
AB  - Hepatic dysfunction in the critically ill patient presents a unique challenge to
      clinicians when designing pharmacotherapeutic treatment plans. Overall, the
      literature regarding drug dosing in critically ill patients with hepatic
      dysfunction is incomplete and current tools available to bedside clinicians have
      limitations. Despite these challenges, rational drug regimens can be implemented
      by critical care nurses who consider the potential impact of hepatic dysfunction
      on drug pharmacokinetics. This information can be applied clinically and careful
      monitoring plans can be implemented to assess a drug for efficacy and safety.
      This article reviews the pharmacokinetic changes that can occur in hepatic
      failure, identifies practical ways to quantify the severity of dysfunction, and
      discusses general drug dosing strategies in this patient population.

PMID- 20691385
TI  - Current and emerging strategies for treating hepatic encephalopathy.
AB  - Hepatic encephalopathy (HE) is caused by liver impairment and has a multitude of
      symptoms in affected patients, including change in level of consciousness,
      intellectual function, and neuromuscular function. Pharmacologic therapy includes
      use of nonabsorbable disaccharides (lactulose and lactitol), and antibiotics such
      as neomycin, paromycin, metronidazole, and rifaximin. Probiotics, acarbose, and
      drugs such as L-carnitine and flumazenil, may also be helpful in treating HE.

PMID- 20691386
TI  - Hepatorenal syndrome: a comprehensive overview for the critical care nurse.
AB  - Over the past 50 years, the pathophysiology and features of the hepatorenal
      syndrome have been illuminated. The syndrome can be divided into 2 distinct
      clinical patterns: a rapidly progressive renal failure with an extremely poor
      prognosis (type 1) and a slow progressive renal failure that correlates with the
      degree of cirrhosis (type 2). Although our understanding of hepatorenal syndrome
      continues to grow, our current methods of treating this condition remain limited
      in their effectiveness. The only definitive therapy is liver transplantation.
      This is a review of the definition, pathophysiology, and current recommendations
      for management of hepatorenal syndrome with the critical care nurse in mind.

PMID- 20691387
TI  - Nutrition support in end-stage liver disease.
AB  - Protein-calorie malnutrition is common in end-stage liver disease, irrespective
      of cause, and adversely affects clinical outcomes. Early diagnosis is important
      to allow appropriate intervention to prevent malnutrition-associated
      complications. Correction of nutrient deficiencies through oral supplementation,
      enteral tube feeding, or parenteral feeding can improve clinical outcomes in this
      patient population. This article addresses the causes of malnutrition, methods
      used to assess nutritional status, and treatment strategies in end-stage liver
      disease.

PMID- 20691389
TI  - Acute liver failure.
AB  - Acute liver failure (ALF) is an uncommon condition involving the rapid
      deterioration of liver functions and coagulation in previously well patients. The
      loss of liver function produces a cascade of systemic effects that rapidly
      overwhelm patients unless acted on. The key to managing patients with ALF
      revolves around having the resources and expertise to manage patients with
      rapidly evolving multiple system failure.

PMID- 20691388
TI  - Medical management of variceal hemorrhage.
AB  - Gastroesophageal variceal hemorrhage is a major complication of portal
      hypertension in 50% to 60% of patients with liver cirrhosis and is a frequent
      cause of mortality in these patients. The prevalence of variceal hemorrhage is
      approximately 5% to 15% yearly, and early variceal rebleeding has a rate of
      occurrence of 30% to 40% within the first 6 weeks. More than 50% of patients who
      survive after the first bleeding episode will experience recurrent bleeding
      within 1 year. Management of gastroesophageal varices should include prevention
      of initial and recurrent bleeding episodes and control of active hemorrhage.
      Therapies used in the management of gastroesophageal variceal hemorrhage may
      include pharmacologic therapy (vasoactive agents, nonselective b-blockers, and
      antibiotic prophylaxis), endoscopic therapy, transjugular intrahepatic
      portosystemic shunt, and shunt surgery. This article focuses primarily on
      pharmacologic management of acute variceal hemorrhage.

PMID- 20691390
TI  - Liver transplant considerations for evaluation, CTP, and MELD.
AB  - The detailed evaluation of a patient for liver transplant candidacy involves
      health care professionals from various disciplines to ensure that liver
      transplantation is optimal for patient morbidity and mortality from the medical
      and psychosocial perspective. The national liver allocation policy is complex and
      should be updated periodically based on continual assessment of outcomes that
      result from current policies. Streamlining of policies and procedures and
      implementing appropriate documentation across all transplant centers is required
      and regulated by National agencies such as OPTN/UNOS and CMS. This ensures safe
      and appropriate organ allocation and the delivery of high-quality transplant
      services.

PMID- 20691391
TI  - The effect of local primary care physician supply on the utilization of
      preventive health services in the United States.
AB  - Little research has examined the effect of physician supply on health-related
      measures at the individual and community level simultaneously. Using telephone
      survey data from six counties in upstate New York, a commuting radius was
      constructed between the zip codes of respondents and their primary care
      physicians. The relationships between local physician supply, the probability of
      having a primary care physician, and receiving preventive health care checks were
      analyzed. Both logistic regression and multilevel modeling results indicated the
      local supply of primary care physicians affects the probability of having a
      primary care physician, which in turn affects preventive healthcare service
      utilization.

PMID- 20691392
TI  - Changes in mood states after coronary artery bypass graft surgery.
AB  - Few studies have investigated the change in mood states, such as anger, fatigue
      and confusion, after coronary artery bypass graft surgery (CABGS). The aim of
      this study was to describe the progression of these mood states over time and to
      determine the factors associated with these trajectories. The Profile of Mood
      States (POMS) was administered to 182 CABGS patients prior to surgery and at two
      and six months post-operatively. Socio-demographic and medical data were
      collected before surgery. Growth curve modelling was used to describe the POMS
      subscale trajectories. Four POMS subscales (tension-anxiety, fatigue-inertia,
      confusion-bewilderment, and vigour-activity) showed rapid improvement over the
      first two months after CABGS followed by a lesser improvement. There was no
      significant change over time for the depression-dejection and anger-hostility
      subscales. Being younger, male, having a manual occupation, and smoking were
      factors associated with poorer pre-operative mood states. Those at risk of
      persistent mood disturbance after CABGS were younger, unpartnered, female and
      those with diabetes. These patients can be identified prior to hospital
      admission.

PMID- 20691393
TI  - The most redundant sequences in human CpG island library are derived from
      mitochondrial genome.
AB  - An altered pattern of epigenetic modifications, such as DNA methylation and
      histone modification, is critical to many common human diseases, including
      cancer. Recently, mitochondrial DNA (mtDNA) was reported to be associated with
      tumorigenesis through epigenetic regulation of methylation patterns. One of the
      promising approaches to study DNA methylation and CpG islands (CGIs) is
      sequencing and analysis of clones derived from the physical library generated by
      methyl-CpG-binding domain proteins and restriction enzyme MseI. In this study, we
      observed that the most redundant sequences of 349 clones in a human CGI library
      were all generated from the human mitochondrial genome. Further analysis
      indicated that there was a 5,845-bp DNA transfer from mtDNA to chromosome 1, and
      all the clones should be the products of a 510-bp MseI fragment, which contained
      a putative CGI of 270 bp. The 510-bp fragment was annotated as part of cytochrome
      c oxidase subunit II (COXII), and phylogenetic analysis of homologous sequences
      containing COXII showed three DNA transfer events from mtDNA to nuclear genome,
      one of which underwent secondary transfer events between different chromosomes.
      These results may further our understanding of how the mtDNA regulates DNA
      methylation in the nucleus.

PMID- 20691394
TI  - Sequence signatures of nucleosome positioning in Caenorhabditis elegans.
AB  - Our recent investigation in the protist Trichomonas vaginalis suggested a DNA
      sequence periodicity with a unit length of 120.9 nt, which represents a sequence
      signature for nucleosome positioning. We now extended our observation in higher
      eukaryotes and identified a similar periodicity of 175 nt in length in
      Caenorhabditis elegans. In the process of defining the sequence compositional
      characteristics, we found that the 10.5-nt periodicity, the sequence signature of
      DNA double helix, may not be sufficient for cross-nucleosome positioning but
      provides essential guiding rails to facilitate positioning. We further dissected
      nucleosome-protected sequences and identified a strong positive purine (AG)
      gradient from the 5'-end to the 3'-end, and also learnt that the nucleosome
      enriched regions are GC-rich as compared to the nucleosome-free sequences as
      purine content is positively correlated with GC content. Sequence
      characterization allowed us to develop a hidden Markov model (HMM) algorithm for
      decoding nucleosome positioning computationally, and based on a set of training
      data from the fifth chromosome of C. elegans, our algorithm predicted 60%-70% of
      the well-positioned nucleosomes, which is 15%-20% higher than random positioning.
      We concluded that nucleosomes are not randomly positioned on DNA sequences and
      yet bind to different genome regions with variable stability, well-positioned
      nucleosomes leave sequence signatures on DNA, and statistical positioning of
      nucleosomes across genome can be decoded computationally based on these sequence
      signatures.

PMID- 20691395
TI  - Genome-wide survey and evolutionary analysis of trypsin proteases in apicomplexan
      parasites.
AB  - Apicomplexa are an extremely diverse group of unicellular organisms that infect
      humans and other animals. Despite the great advances in combating infectious
      diseases over the past century, these parasites still have a tremendous social
      and economic burden on human societies, particularly in tropical and subtropical
      regions of the world. Proteases from apicomplexa have been characterized at the
      molecular and cellular levels, and central roles have been proposed for proteases
      in diverse processes. In this work, 16 new genes encoding for trypsin proteases
      are identified in 8 apicomplexan genomes by a genome-wide survey. Phylogenetic
      analysis suggests that these genes were gained through both intracellular gene
      transfer and vertical gene transfer. Identification, characterization and
      understanding of the evolutionary origin of protease-mediated processes are
      crucial to increase the knowledge and improve the strategies for the development
      of novel chemotherapeutic agents and vaccines.

PMID- 20691396
TI  - Computational identification of miRNAs and their target genes from expressed
      sequence tags of tea (Camellia sinensis).
AB  - MicroRNAs (miRNAs) are a newly identified class of small non-protein-coding post
      transcriptional regulatory RNA in both plants and animals. The use of
      computational homology based search for expressed sequence tags (ESTs) with the
      Ambros empirical formula and other structural feature criteria filter is a
      suitable combination towards the discovery and isolation of conserved miRNAs from
      tea and other plant species whose genomes are not yet sequenced. In the present
      study, we blasted the database of tea (Camellia sinensis) ESTs to search for
      potential miRNAs, using previously known plant miRNAs. For the first time, four
      candidate miRNAs from four families were identified in tea. Using the newly
      identified miRNA sequences, a total of 30 potential target genes were identified
      for 11 miRNA families; 6 of these predicted target genes encode transcription
      factors (20%), 16 target genes appear to play roles in diverse physiological
      processes (53%) and 8 target genes have hypothetical or unknown functions (27%).
      These findings considerably broaden the scope of understanding the functions of
      miRNA in tea.

PMID- 20691397
TI  - ZiF-Predict: a web tool for predicting DNA-binding specificity in C2H2 zinc
      finger proteins.
AB  - Engineering zinc finger protein motifs for specific DNA targets in genomes is
      critical in the field of genome engineering. We have developed a computational
      method for predicting recognition helices for C2H2 zinc fingers that bind to
      specific target DNA sites. This prediction is based on artificial neural network
      using an exhaustive dataset of zinc finger proteins and their target DNA
      triplets. Users can select the option for two or three zinc fingers to be
      predicted either in a modular or synergistic fashion for the input DNA sequence.
      This method would be valuable for researchers interested in designing specific
      zinc finger transcription factors and zinc finger nucleases for several
      biological and biomedical applications. The web tool ZiF-Predict is available
      online at http://web.iitd.ac.in/~sundar/zifpredict/.

PMID- 20691398
TI  - PsRNA: a computing engine for the comparative identification of putative small
      RNA locations within intergenic regions.
AB  - Small RNAs (sRNAs) are non-coding transcripts exerting their functions in the
      cells directly. Identification of sRNAs is a difficult task due to the lack of
      clear sequence and structural biases. Most sRNAs are identified within genus
      specific intergenic regions in related genomes. However, several of these regions
      remain un-annotated due to lack of sequence homology and/or potent statistical
      identification tools. A computational engine has been built to search within the
      intergenic regions to identify and roughly annotate new putative sRNA regions in
      Enterobacteriaceae genomes. It utilizes experimentally known sRNA data and their
      flanking genes/KEGG Orthology (KO) numbers as templates to identify similar sRNA
      regions in related query genomes. The search engine not only has the capability
      to locate putative intergenic regions for specific sRNAs, but also has the
      potency to locate conserved, shuffled or deleted gene clusters in query genomes.
      Because it uses the KO terms for locating functionally important regions such as
      sRNAs, any further KO number assignment to additional genes will increase the
      sensitivity. The PsRNA server is used for the identification of putative sRNA
      regions through the information retrieved from the sRNA of interest. The
      computing engine is available online at
      http://bioserver1.physics.iisc.ernet.in/psrna/ and http://bicmku.in:8081/psrna/.

PMID- 20691399
TI  - BiDiBlast: comparative genomics pipeline for the PC.
AB  - Bi-directional BLAST is a simple approach to detect, annotate, and analyze
      candidate orthologous or paralogous sequences in a single go. This procedure is
      usually confined to the realm of customized Perl scripts, usually tuned for UNIX
      like environments. Porting those scripts to other operating systems involves
      refactoring them, and also the installation of the Perl programming environment
      with the required libraries. To overcome these limitations, a data pipeline was
      implemented in Java. This application submits two batches of sequences to local
      versions of the NCBI BLAST tool, manages result lists, and refines both bi
      directional and simple hits. GO Slim terms are attached to hits, several
      statistics are derived, and molecular evolution rates are estimated through PAML.
      The results are written to a set of delimited text tables intended for further
      analysis. The provided graphic user interface allows a friendly interaction with
      this application, which is documented and available to download at
      http://moodle.fct.unl.pt/course/view.php?id=2079 or
      https://sourceforge.net/projects/bidiblast/ under the GNU GPL license.

PMID- 20691400
TI  - [Manual medicine-osteopathy in France].

PMID- 20691401
TI  - Manual medicine - osteopathy in France organization - education - fields of
      expertise.
AB  - Manual medicine-osteopathy (MMO) is of keen interest among young doctors,
      generalists and specialists alike. Through a discerning semiological approach,
      MMO allows non-pharmaceutical physical treatments to be proposed for many
      musculoskeletal pathologies. In March 2007, some manual therapies (e.g.,
      osteopathy), until then the exclusive preserve of physicians, were recognized in
      France as a part of the field of professional expertise of non-physicians. This
      new opening of the manual medicine profession must make non-physicians and
      physicians aware of their responsibilities.

PMID- 20691402
TI  - Whole-genome genetic diversity in a sample of Australians with deep Aboriginal
      ancestry.
AB  - Australia was probably settled soon after modern humans left Africa, but details
      of this ancient migration are not well understood. Debate centers on whether the
      Pleistocene Sahul continent (composed of New Guinea, Australia, and Tasmania) was
      first settled by a single wave followed by regional divergence into Aboriginal
      Australian and New Guinean populations (common origin) or whether different parts
      of the continent were initially populated independently. Australia has been the
      subject of relatively few DNA studies even though understanding regional
      variation in genomic structure and diversity will be important if disease
      association mapping methods are to be successfully evaluated and applied across
      populations. We report on a genome-wide investigation of Australian Aboriginal
      SNP diversity in a sample of participants from the Riverine region. The
      phylogenetic relationship of these Aboriginal Australians to a range of other
      global populations demonstrates a deep common origin with Papuan New Guineans and
      Melanesians, with little evidence of substantial later migration until the very
      recent arrival of European colonists. The study provides valuable and robust
      insights into an early and important phase of human colonization of the globe. A
      broader survey of Australia, including diverse geographic sample populations,
      will be required to fully appreciate the continent's unique population history
      and consequent genetic heritage, as well as the importance of both to the
      understanding of health issues.

PMID- 20691403
TI  - Homozygous nonsense mutations in TWIST2 cause Setleis syndrome.
AB  - The focal facial dermal dysplasias (FFDDs) are a group of inherited developmental
      disorders in which the characteristic diagnostic feature is bitemporal scar-like
      lesions that resemble forceps marks. To date, the genetic defects underlying
      these ectodermal dysplasias have not been determined. To identify the gene defect
      causing autosomal-recessive Setleis syndrome (type III FFDD), homozygosity
      mapping was performed with genomic DNAs from five affected individuals and 26
      members of the consanguineous Puerto Rican (PR) family originally described by
      Setleis and colleagues. Microsatellites D2S1397 and D2S2968 were homozygous in
      all affected individuals, mapping the disease locus to 2q37.3. Haplotype analyses
      of additional markers in the PR family and a consanguineous Arab family further
      limited the disease locus to approximately 3 Mb between D2S2949 and D2S2253. Of
      the 29 candidate genes in this region, the bHLH transcription factor, TWIST2, was
      initially sequenced on the basis of its known involvement in murine facial
      development. Homozygous TWIST2 nonsense mutations, c.324C>T and c.486C>T, were
      identified in the affected members of the Arab and PR families, respectively.
      Characterization of the expressed mutant proteins, p.Q65X and p.Q119X, by
      electrophoretic mobility shift assays and immunoblot analyses indicated that they
      were truncated and unstable. Notably, Setleis syndrome patients and Twist2
      knockout mice have similar facial features, indicating the gene's conserved role
      in mammalian development. Although human TWIST2 and TWIST1 encode highly
      homologous bHLH transcription factors, the finding that TWIST2 recessive
      mutations cause an FFDD and dominant TWIST1 mutations cause Saethre-Chotzen
      craniocynostosis suggests that they function independently in skin and bone
      development.

PMID- 20691404
TI  - Loss of corneodesmosin leads to severe skin barrier defect, pruritus, and atopy:
      unraveling the peeling skin disease.
AB  - Generalized peeling skin disease is an autosomal-recessive ichthyosiform
      erythroderma characterized by lifelong patchy peeling of the skin. After genome
      wide linkage analysis, we have identified a homozygous nonsense mutation in CDSN
      in a large consanguineous family with generalized peeling skin, pruritus, and
      food allergies, which leads to a complete loss of corneodesmosin. In contrast to
      hypotrichosis simplex, which can be associated with specific dominant CDSN
      mutations, peeling skin disease is characterized by a complete loss of CDSN
      expression. The skin phenotype is consistent with a recent murine Cdsn knockout
      model. Using three-dimensional human skin models, we demonstrate that lack of
      corneodesmosin causes an epidermal barrier defect supposed to account for the
      predisposition to atopic diseases, and we confirm the role of corneodesmosin as a
      decisive epidermal adhesion molecule. Therefore, peeling skin disease will
      represent a new model disorder for atopic diseases, similarly to Netherton
      syndrome and ichthyosis vulgaris in the recent past.

PMID- 20691405
TI  - Mutations in PVRL4, encoding cell adhesion molecule nectin-4, cause ectodermal
      dysplasia-syndactyly syndrome.
AB  - Ectodermal dysplasias form a large disease family with more than 200 members. The
      combination of hair and tooth abnormalities, alopecia, and cutaneous syndactyly
      is characteristic of ectodermal dysplasia-syndactyly syndrome (EDSS). We used a
      homozygosity mapping approach to map the EDSS locus to 1q23 in a consanguineous
      Algerian family. By candidate gene analysis, we identified a homozygous mutation
      in the PVRL4 gene that not only evoked an amino acid change but also led to exon
      skipping. In an Italian family with two siblings affected by EDSS, we further
      detected a missense and a frameshift mutation. PVRL4 encodes for nectin-4, a cell
      adhesion molecule mainly implicated in the formation of cadherin-based adherens
      junctions. We demonstrated high nectin-4 expression in hair follicle structures,
      as well as in the separating digits of murine embryos, the tissues mainly
      affected by the EDSS phenotype. In patient keratinocytes, mutated nectin-4 lost
      its capability to bind nectin-1. Additionally, in discrete structures of the hair
      follicle, we found alterations of the membrane localization of nectin-afadin and
      cadherin-catenin complexes, which are essential for adherens junction formation,
      and we found reorganization of actin cytoskeleton. Together with cleft lip and/or
      palate ectodermal dysplasia (CLPED1, or Zlotogora-Ogur syndrome) due to an
      impaired function of nectin-1, EDSS is the second known "nectinopathy" caused by
      mutations in a nectin adhesion molecule.

PMID- 20691406
TI  - Microdeletions of 3q29 confer high risk for schizophrenia.
AB  - Schizophrenia (SZ) is a severe psychiatric illness that affects approximately 1%
      of the population and has a strong genetic underpinning. Recently, genome-wide
      analysis of copy-number variation (CNV) has implicated rare and de novo events as
      important in SZ. Here, we report a genome-wide analysis of 245 SZ cases and 490
      controls, all of Ashkenazi Jewish descent. Because many studies have found an
      excess burden of large, rare deletions in cases, we limited our analysis to
      deletions over 500 kb in size. We observed seven large, rare deletions in cases,
      with 57% of these being de novo. We focused on one 836 kb de novo deletion at
      chromosome 3q29 that falls within a 1.3-1.6 Mb deletion previously identified in
      children with intellectual disability (ID) and autism, because increasing
      evidence suggests an overlap of specific rare copy-number variants (CNVs) between
      autism and SZ. By combining our data with prior CNV studies of SZ and analysis of
      the data of the Genetic Association Information Network (GAIN), we identified six
      3q29 deletions among 7545 schizophrenic subjects and one among 39,748 controls,
      resulting in a statistically significant association with SZ (p = 0.02) and an
      odds ratio estimate of 17 (95% confidence interval: 1.36-1198.4). Moreover, this
      3q29 deletion region contains two linkage peaks from prior SZ family studies, and
      the minimal deletion interval implicates 20 annotated genes, including PAK2 and
      DLG1, both paralogous to X-linked ID genes and now strong candidates for SZ
      susceptibility.

PMID- 20691407
TI  - Haploinsufficiency of HDAC4 causes brachydactyly mental retardation syndrome,
      with brachydactyly type E, developmental delays, and behavioral problems.
AB  - Brachydactyly mental retardation syndrome (BDMR) is associated with a deletion
      involving chromosome 2q37. BDMR presents with a range of features, including
      intellectual disabilities, developmental delays, behavioral abnormalities, sleep
      disturbance, craniofacial and skeletal abnormalities (including brachydactyly
      type E), and autism spectrum disorder. To date, only large deletions of 2q37 have
      been reported, making delineation of a critical region and subsequent
      identification of candidate genes difficult. We present clinical and molecular
      analysis of six individuals with overlapping deletions involving 2q37.3 that
      refine the critical region, reducing the candidate genes from >20 to a single
      gene, histone deacetylase 4 (HDAC4). Driven by the distinct hand and foot
      anomalies and similar cognitive features, we identified other cases with clinical
      findings consistent with BDMR but without a 2q37 deletion, and sequencing of
      HDAC4 identified de novo mutations, including one intragenic deletion probably
      disrupting normal splicing and one intragenic insertion that results in a
      frameshift and premature stop codon. HDAC4 is a histone deacetylase that
      regulates genes important in bone, muscle, neurological, and cardiac development.
      Reportedly, Hdac4(-/-) mice have severe bone malformations resulting from
      premature ossification of developing bones. Data presented here show that
      deletion or mutation of HDAC4 results in reduced expression of RAI1, which causes
      Smith-Magenis syndrome when haploinsufficient, providing a link to the
      overlapping findings in these disorders. Considering the known molecular function
      of HDAC4 and the mouse knockout phenotype, taken together with deletion or
      mutation of HDAC4 in multiple subjects with BDMR, we conclude that
      haploinsufficiency of HDAC4 results in brachydactyly mental retardation syndrome.

PMID- 20691408
TI  - Resident training for eclampsia and magnesium toxicity management: simulation or
      traditional lecture?
AB  - OBJECTIVE: To compare eclampsia and magnesium toxicity management among residents
      randomly assigned to lecture or simulation-based education. STUDY DESIGN:
      Statified by year, residents (n = 38) were randomly assigned to 3 educational
      intervention groups: Simulation->Lecture, Simulation, and Lecture.
      Postintervention simulations were performed for all and scored using standardized
      lists. Maternal, fetal, eclampsia management, and magnesium toxcity scores were
      assigned. Mann-Whitney U, Wilcoxon rank sum and chi(2) tests were used for
      analysis. RESULTS: Postintervention maternal (16 and 15 vs 12; P < .05) and
      eclampsia (19 vs 16; P < .05) scores were significantly better in simulation
      based compared with lecture groups. Postintervention magnesium toxcitiy and fetal
      scores were not different among groups. Lecture added to simulation did not lead
      to incremental benefit when eclampsia scores were compared between Simulation
      >Lecture and Simulation (19 vs 19; P = nonsignificant). CONCLUSION: Simulation
      training is superior to traditional lecture alone for teaching crucial skills for
      the optimal management of both eclampsia and magnesium toxicity, 2 life
      threatening obstetric emergencies.

PMID- 20691409
TI  - Treatment with docosahexaenoic acid after hypoxia-ischemia improves forepaw
      placing in a rat model of perinatal hypoxia-ischemia.
AB  - OBJECTIVE: Docosahexaenoic acid (DHA) is a dietary fatty acid with
      neuroprotective properties. We hypothesized that DHA treatment after hypoxia
      ischemia would improve function and reduce brain volume loss in a perinatal rat
      model. STUDY DESIGN: Seven-day-old Wistar rat pups from 7 litters (n = 84)
      underwent right carotid ligation, followed by 8% O(2) for 90 minutes. Fifteen
      minutes after hypoxia-ischemia, pups were divided into 3 treatment groups
      (intraperitoneal injections of DHA 1, 2.5, or 5 mg/kg) and 2 control groups (25%
      albumin or saline). At 14 days, rats underwent vibrissae-stimulated forepaw
      placing testing, and bilateral regional volumes were calculated for cortex,
      striatum, hippocampus, and hemisphere. RESULTS: Posthypoxia-ischemia treatment
      with DHA acid significantly improved vibrissae forepaw placing (complete
      responses: 8.5 +/- 2 treatment vs 7.4 +/- 2 controls; normal = 10; P = .032, t
      test). Postinjury DHA treatment did not attenuate brain volume loss in any
      region. CONCLUSION: Posthypoxia-ischemia DHA treatment significantly improves
      functional outcome.

PMID- 20691410
TI  - Screening for preeclampsia using first-trimester serum markers and uterine artery
      Doppler in nulliparous women.
AB  - OBJECTIVE: To evaluate the screening accuracy of pregnancy hypertensive disorders
      by maternal serum biomarkers and uterine artery Doppler in the first trimester.
      STUDY DESIGN: Prospectively enrolled nulliparous women had uterine artery Doppler
      and serum measured at 11-13 weeks. Maternal characteristics, uterine artery
      Doppler, and serum placental biomarkers (pregnancy-associated plasma protein-A,
      Inhibin-A, placental protein 13, A disintegrin and metalloprotease 12, free beta
      hCG, placental growth factor) were recorded. RESULTS: Among 893 women, 20 (2.2%)
      had gestational hypertension developed and 40 (4.5%) had preeclampsia developed,
      including 9 (1.0%) early-onset preeclampsia and 16 (1.8%) severe preeclampsia. A
      combined screening model with clinical characteristics, pregnancy-associated
      plasma protein-A, Inhibin-A, and placental growth factor could detect 75% of
      early-onset preeclampsia at a 10% false-positive rate. After adjustment for
      clinical variables, uterine artery Doppler, placental protein 13, and A
      disintegrin and metalloprotease 12 did not improve the diagnostic accuracy.
      CONCLUSION: A combination of clinical characteristics and first-trimester
      maternal serum biomarkers (pregnancy-associated plasma protein-A, Inhibin-A, and
      placental growth factor) provides an accurate screening for early-onset
      preeclampsia in nulliparous women.

PMID- 20691411
TI  - Myocardial dysfunction in fetuses exposed to intraamniotic infection: new
      insights from tissue Doppler and strain imaging.
AB  - OBJECTIVE: The purpose of this study was to assess myocardial function of fetuses
      who were exposed to intraamniotic infection compared with fetuses of
      uncomplicated pregnancies by the application of tissue Doppler and strain rate
      (SR) imaging. STUDY DESIGN: We evaluated the right ventricular function of
      fetuses with preterm premature rupture of membranes and proven intraamniotic
      infection (n = 12 fetuses) and healthy fetuses (n = 27). Tissue Doppler
      velocities during early diastolic relaxation (E(m)) and atrial contraction (A(m))
      and early diastolic SR were measured as indices of diastolic function, whereas
      the peak systolic strain and SR were used as parameters of systolic function.
      RESULTS: Fetuses with intraamniotic infection exhibit impairment in both
      diastolic and systolic performance, which was characterized by increased
      diastolic compliance (increased E(m)/A(m) ratio, increased early diastolic SR
      compared with the control fetuses), decreased systolic contractile function
      (reduced systolic strain and SR), and longitudinal myocardial dyskinesia.
      CONCLUSION: New echocardiographic tools suggest that fetal heart is a target
      organ in the context of intraamniotic infection.

PMID- 20691412
TI  - Steroid profiling in preeclamptic women: evidence for aromatase deficiency.
AB  - OBJECTIVE: Experimental data have revealed the critical role played by 2-methoxy
      estradiol, a metabolite of 17beta-estradiol, in the pathophysiology of
      preeclampsia. We used gas chromatography/mass spectrometry to measure a whole
      panel of hormonal steroids in the plasma from women during the third trimester of
      their pregnancy. STUDY DESIGN: The population study consists of 24 pregnant
      patients with different outcomes: normal, or complicated by isolated preeclampsia
      or by severe preeclampsia with Hemolysis Enzyme Liver Low Platelets (HELLP)
      syndrome. RESULTS: 17beta-estradiol was reduced by 50% in isolated preeclampsia,
      and by 70% in severe preeclampsia with HELLP syndrome (normal: 8.54 +/- 0.9
      ng/mL; isolated preeclampsia: 4.65 +/- 1.0 ng/mL; severe preeclampsia with HELLP
      syndrome: 2.64 +/- 0.4 ng/mL), as is estrone. Downstream, 2-methoxy-estradiol was
      decreased only in severe preeclampsia with HELLP syndrome. The concentrations of
      estrone and 17beta-estradiol precursors were comparable between groups,
      suggesting that placental aromatase is deficient in preeclampsia. CONCLUSION: The
      gradual decrease of estrogen levels with increasing severity of preeclampsia
      suggests an impairment of placental steroidogenesis.

PMID- 20691413
TI  - Genetic variation in solute carrier genes is associated with preeclampsia.
AB  - OBJECTIVE: The objective of the study was to evaluate allelic variation in 26
      members of the solute carrier (SLC) gene family for an association with
      preeclampsia. STUDY DESIGN: Preeclampsia cases were women with mild or severe
      preeclampsia. Controls were enrolled from women without hypertension-related
      complications who presented for delivery at term (>=37 weeks). The association
      between preeclampsia and SLC gene single-nucleotide polymorphisms (SNPs) and
      haplotypes was evaluated by logistic regression models. RESULTS: Rs4957061 in
      SLC9A3 was significantly associated with a reduced risk of preeclampsia in whites
      (T allele, P = .002; odds ratio [OR], 0.33; 95% confidence interval [CI], 0.16
      0.67). For SLC4A1 in blacks, the G allele of rs2074107 (P = .004; OR, 1.56; 95%
      CI, 1.15-2.12) and the A allele of rs2857078 (P < .001; OR, 1.67; 95% CI, 1.27
      2.17) were significantly associated with preeclampsia. Also in blacks, rs10066650
      in SLCO4C1 (G allele, P = .002; OR, 1.72; 95% CI, 1.21-2.46) was significantly
      associated with increased risk. Sliding window haplotype analyses identified
      significantly associated haplotypes in these genes. CONCLUSION: SNPs and
      haplotypes in SLC9A3 in whites and SLC4A1 and SLCO4C1 in blacks are significantly
      associated with preeclampsia.

PMID- 20691414
TI  - Parity negatively impacts vaginal mechanical properties and collagen structure in
      rhesus macaques.
AB  - OBJECTIVE: The purpose of this study was to determine the impact of parity on
      mechanical behavior of the vagina and to correlate these findings with
      alterations in collagen structure. STUDY DESIGN: Mechanical properties of 5
      nulliparous and 6 parous rhesus macaques were derived from uniaxial tensile
      tests. Collagen ratios and alignment were quantified by quantitative fluorescent
      microscopy and picrosirius red staining. Outcomes were compared by the Student t
      test or Mann Whitney U test (P < .05) and Spearman's rho for correlation
      coefficients. RESULTS: Mechanical properties were inferior in a parous vs
      nulliparous vagina with decreased tangent modulus (P = .03), tensile strength (P
      < .001), and strain energy density (P = .006). Although no difference in collagen
      ratios (P = .26) were observed, collagen alignment decreased with parity (P =
      .06). Worsening pelvic organ support negatively correlated with decreasing
      collagen alignment (r(2) = -0.66) and mechanical properties (r(2) = -0.67).
      CONCLUSION: Vaginal parity is associated with inferior tissue mechanics and loss
      of collagen alignment. Such behavior likely predisposes to the development of
      pelvic organ prolapse.

PMID- 20691415
TI  - Complete trisomy 21 vs translocation Down syndrome: a comparison of modes of
      ascertainment.
AB  - OBJECTIVE: To compare the indications for invasive prenatal testing resulting in
      the detection of translocation Down syndrome and complete trisomy 21. STUDY
      DESIGN: This case control study was based on a large amniocentesis and chorionic
      villi samples database (n = 534,795). All specimens with translocation Down
      syndrome (n = 203) comprised the translocation group and were compared with a
      maternal age-matched group (4 to 1, n = 812) in which complete trisomy 21 was
      detected. Women with a normal karyotype were randomly selected (n = 812) and
      served as controls. Indications for invasive testing were compared among the 3
      paired groups using chi(2) analysis. RESULTS: There were no differences in the
      incidence of abnormal first- and second-trimester screening tests between the
      translocation Down syndrome and the complete trisomy 21 groups. History of prior
      aneuploidy was significantly more frequent in the translocation Down syndrome
      group, as compared with either complete trisomy 21 fetuses or normal controls.
      CONCLUSION: Fetuses with translocation Down syndrome present with the same
      screening abnormalities as fetuses with complete trisomy 21.

PMID- 20691416
TI  - Pelvic magnetic resonance imaging for assessment of the efficacy of the Prolift
      system for pelvic organ prolapse.
AB  - OBJECTIVE: The purpose of this study was to compare pre- and postoperative pelvic
      organ prolapse-quantification (POP-Q) and magnetic resonance imaging (MRI)
      measurements in patients who undergo total Prolift (Ethicon, Inc, Somerville, NJ)
      colpopexy. STUDY DESIGN: Pre- and postoperative MRI and POP-Q examinations were
      performed on patients with stage 2 or greater prolapse who underwent the Prolift
      procedure. MRI measurements were taken at maximum descent. Correlations between
      changes in MRI and POP-Q measurements were determined. RESULTS: Ten subjects were
      enrolled. On MRI, statistically significant changes were seen with cystocele,
      enterocele, and apex. Statistically significant changes were seen on POP-Q
      measurements for Aa, Ba, C, Ap, Bp, and GH. Positive correlations were
      demonstrated between POP-Q and MRI changes. Minimal tissue reaction was seen on
      MRI. CONCLUSION: The Prolift system is effective in the surgical management of
      pelvic organ prolapse as measured by POP-Q and MRI. Postoperative MRIs support
      the inert nature of polypropylene mesh.

PMID- 20691417
TI  - Keratocyte density after laser-assisted subepithelial keratectomy with mitomycin
      C.
AB  - PURPOSE: To study the effects of laser-assisted subepithelial keratectomy (LASEK)
      with mitomycin C (MMC) on the keratocyte population. DESIGN: Prospective,
      nonrandomized, interventional, comparative case series. METHODS: Fifty-six eyes
      treated at Vissum Santa Hortensia, Madrid, Spain, were included in the study. We
      compared 28 eyes treated with LASEK with intraoperative 0.02% MMC versus 28 non
      treated eyes. Keratocyte density was measured 3 months after the surgery in the
      anterior, mid, and posterior stroma and was compared with the corresponding
      layers in the control eyes. The anterior layer in the LASEK group was compared
      with 2 layers in the control group: the most anterior stromal layer and the 80
      MUm-deep layer, because that was the mean ablation depth performed in eyes that
      underwent LASEK. RESULTS: We found a statistically significantly lower keratocyte
      population in the most anterior stromal layer after LASEK with MMC compared with
      both the most anterior stromal layer and the 80 MUm-deep layer in controls. On
      the contrary, the treated group showed a significantly higher keratocyte density
      in both the mid stroma and the deep stroma. The comparison between the average
      densities through the entire cornea showed a significantly higher keratocyte
      population in the LASEK with MMC group. CONCLUSIONS: LASEK with MMC seems to
      cause a decrease in the anterior stromal cells 3 months after the surgery
      compared with nonoperated corneas. There seems to be a compensating proliferation
      of keratocytes in the deeper corneal layers, suggesting that the ability of
      keratocytes to repopulate the cornea is maintained after the surgical procedure.

PMID- 20691418
TI  - Pain perception at laser treatment of peripheral retinal degenerations with green
      and infrared wavelengths.
AB  - PURPOSE: To compare the pain perception at laser treatment of peripheral retinal
      degenerations with green (532-nm) and infrared (810-nm) wavelengths. DESIGN:
      Prospective randomized clinical trial. METHODS: Sequential patients with
      indications for photocoagulation of bilateral peripheral retinal degenerations
      were invited to participate in the study. Thirty patients (60 eyes) were enrolled
      in the study. Each patient had 1 eye treated with infrared laser (diode, 810-nm
      wavelength) and the other eye treated with green laser (frequency-doubled solid
      state laser, diode-pumped, with 532-nm wavelength). The eyes were randomized to
      infrared or green wavelengths. The right eye was the first treated in all cases
      regardless of the wavelength arrangement. Immediately after photocoagulation of
      each eye, the patient was asked to grade pain perception according to an 11-point
      (ie, 0-10) numerical rating scale (NRS), with 0 meaning "No pain" and 10 meaning
      "Pain as bad as you can imagine." The primary outcome was the assessment of pain.
      RESULTS: The mean grading of pain perception was 2.80 (SD 1.27; mode and median =
      2) to green wavelengths and 5.07 (SD 1.36; mode = 4 and median = 5) to infrared
      wavelengths (P < .001). CONCLUSIONS: The results showed a statistically and
      clinically significant difference of pain perception between the 2 groups, with
      advantage to the green laser group.

PMID- 20691419
TI  - In vivo confocal microscopic evaluation of morphologic changes and dendritic cell
      distribution in pterygium.
AB  - PURPOSE: To observe morphologic changes and the distribution of dendritic cells
      in pterygium using in vivo laser scanning confocal microscopy (LSCM). DESIGN:
      Prospective comparative study. METHODS: Twenty-six eyes of 26 patients with
      pterygium and 17 eyes of 17 healthy subjects were recruited. Using LSCM, in vivo
      images of the pterygium and adjacent clear cornea were captured. The density of
      basal corneal epithelial cells and keratocytes in the anterior and posterior
      stroma and the density of dendritic cells in the pterygium and adjacent clear
      cornea were determined. In the controls, the central cornea and nasal bulbar
      conjunctiva were imaged. The density of basal corneal epithelial cells,
      keratocytes, and dendritic cells was evaluated. RESULTS: Morphologic alterations
      of the sub-basal nerve plexus were observed in pterygium. The density of basal
      corneal epithelial cells and anterior keratocytes in pterygium was 5359.0 +/-
      543.1 cells/mm2 and 407.4 +/- 188.7 cells/mm2 respectively, which was
      significantly lower than that in the controls (P < .001). The density of
      dendritic cells in the clear corneas of pterygia was 60.3 +/- 25.5 cells/mm2,
      which was significantly higher than the 23.6 +/- 11.1 cells/mm2 in the central
      corneas of controls (P < .001). The dendritic cell density in the pterygium was
      significantly higher than the density in the nasal bulbar conjunctiva of controls
      (P < .001). CONCLUSIONS: Histopathologic alterations and increased dendritic
      cells were evident in pterygium and the adjacent clear cornea by in vivo LSCM. In
      vivo LSCM was found to be an effective method of observing the morphologic
      alterations of pterygium.

PMID- 20691420
TI  - Identification of new pathogens in the intraocular fluid of patients with
      uveitis.
AB  - PURPOSE: To determine infectious causes in patients with uveitis of unknown
      origin by intraocular fluids analysis. DESIGN: Case-control study. METHODS:
      Ocular fluids from 139 patients suspected of infectious uveitis, but negative for
      herpes simplex virus, varicella-zoster virus, cytomegalovirus, and Toxoplasma
      gondii by polymerase chain reaction and/or antibody analysis in intraocular
      fluids, were assessed for the presence of 18 viruses and 3 bacteria by real-time
      polymerase chain reaction (PCR). The ocular fluids from 48 patients with uveitis
      of known etiology or with cataract were included as controls. RESULTS: Positive
      PCR results were found for Epstein-Barr virus, for rubella virus, and for human
      herpesvirus 6 each in 1 patient and for human parechovirus in 4 patients. Of the
      human parechovirus-positive patients, 1 was immunocompromised and had panuveitis.
      The other 3 patients were immunocompetent and had anterior uveitis, all with
      corneal involvement. CONCLUSIONS: Human parechovirus might be associated with
      infectious (kerato)uveitis.

PMID- 20691421
TI  - Patients with an acute zonal occult outer retinopathy-like illness rapidly
      improve with valacyclovir treatment.
AB  - PURPOSE: To describe 3 cases of an acute zonal occult outer retinopathy-like
      illness responsive to valacyclovir hydrochloride. DESIGN: Retrospective,
      interventional case series. METHODS: Three patients were treated with
      valacyclovir and monitored by clinical examination, Goldmann visual field
      testing, and electroretinography. RESULTS: Patients with an acute zonal occult
      outer retinopathy-like illness presented following progressive vision loss. This
      course was immediately reversed by treatment with oral valacyclovir, and visual
      acuity and visual field improved significantly at 1 week and 1 month. Patients
      remained stable without treatment during a follow-up period ranging from 1 to 3
      years. CONCLUSIONS: Some conditions with features of acute zonal occult outer
      retinopathy may be attributable to a subacute herpetic viral infection that is
      responsive to oral antiviral medication.

PMID- 20691422
TI  - Visual performances with monofocal, accommodating, and multifocal intraocular
      lenses in patients with unilateral cataract.
AB  - PURPOSE: To compare the visual performance of patients with unilateral cataract
      following implantation of monofocal, accommodating, refractive, and diffractive
      multifocal intraocular lenses (IOL). DESIGN: Prospective nonrandomized clinical
      trial. METHODS: Eighty-seven patients with unilateral cataract were enrolled in 4
      groups for phacoemulsification and IOL implantation. Twenty-four patients had
      monofocal (Alcon Acrysof) (group 1), 21 patients had accommodating (Human Optics
      1CU) (group 2), 22 patients had diffractive multifocal (Tecnis ZM900) (group 3),
      and 20 patients had refractive multifocal (AMO Rezoom) (group 4) IOL
      implantations. Ages of patients were between 40 and 70. Parameters analyzed at
      the 18th postoperative month were subjective refractions, monocular and binocular
      distance, intermediate and near uncorrected visual acuities, monocular distance
      and near best-corrected visual acuities, monocular distance-corrected
      intermediate and near visual acuities, stereopsis, visual complaints, and
      spectacle dependency. RESULTS: No significant difference was observed between
      distance and near best-corrected visual acuities of IOL groups, and between
      intermediate visual acuities of groups 2, 3, and 4. Groups 3 and 4 had
      statistically better near vision than the other groups (P < .05). No significant
      difference was observed between near visual acuities of groups 3 and 4. Number of
      patients with better stereoscopic function, spectacle independence, and
      complaints of halo in groups 3 and 4 was significantly higher than in other
      groups (P < .05). CONCLUSIONS: Multifocal IOLs provide better stereopsis, higher
      spectacle independence rates, and satisfactory functional vision over a broad
      range of distances in presbyopic patients with unilateral cataract compared with
      the monofocal and accommodating IOLs.

PMID- 20691423
TI  - Impact of age-related macular degeneration on vision-specific quality of life:
      Follow-up from the 10-year and 15-year visits of the Study of Osteoporotic
      Fractures.
AB  - PURPOSE: To assess vision-specific quality of life (QOL), based on abbreviated
      surveys derived from the National Eye Institute Visual Function Questionnaire
      (NEI-VFQ), in a cohort of United States women who participated in the Study of
      Osteoporotic Fractures. DESIGN: Prospective, observational cohort study. METHODS:
      Age-related macular degeneration (AMD) status, based on a 3-level classification
      (no AMD, early AMD, late AMD), and vision-specific QOL, based on abbreviated NEI
      VFQ surveys, were calculated for 1674 women enrolled in the Study of Osteoporotic
      Fractures at 4 centers within the United States who had gradable fundus
      photographs at both the 10-year and 15-year follow-up visits. The associations
      among 5-year changes in NEI-VFQ composite scores, change in AMD status, and
      distance visual acuity were examined. RESULTS: Compared with study participants
      without AMD at both visits, study participants with late AMD at both visits and
      those who progressed from early AMD to late AMD demonstrated the greatest
      declines in adjusted NEI-VFQ composite scores, up to a mean decrease of 16.2 from
      a scale of 100. Visual acuity declines also were most prominent for patients with
      late AMD at both visits and for those who progressed from early AMD to late AMD.
      Change in visual acuity was found to correlate significantly with change in
      vision-specific QOL. CONCLUSIONS: The abbreviated NEI-VFQ surveys provide
      reliable assessments of vision-specific QOL in AMD patients. The decline in
      vision-specific QOL associated with the progression of AMD is clinically
      meaningful.

PMID- 20691425
TI  - Work hours, workload, sleep and fatigue in Australian Rail Industry employees.
AB  - Research suggests that less than 5 h sleep in the 24 h prior to work and/or more
      than 16 h of wakefulness can significantly increase the likelihood of fatigue
      related impairment and error at work. Studies have also shown exponential safety
      declines with time on shift, with roughly double the likelihood of accident or
      injury after 10 h relative to the first 8h. While it is acknowledged that reduced
      sleep, increased wakefulness and longer work hours produce work-related fatigue,
      few studies have examined the impact of workload on this relationship. Studies in
      the rail industry have focused on drivers. This study investigated fatigue in a
      large sample of Australian Rail Industry Employees. Participants were from four
      companies (n = 90: 85m, 5f; mean age 40.2 +/- 8.6 y). Data was analysed for a
      total of 713 shifts. Subjects wore wrist actigraphs and completed sleep and work
      diaries for 14-days. They also completed the Samn-Perelli Fatigue Scale at the
      beginning and end of shifts, and the NASA-TLX workload scale at least twice
      during each shift. Average (+/-SD) sleep length (7.2 +/- 2.6h), prior wake at
      shift end (12.0 +/- 4.7h), shift duration (8.0 +/- 1.3) and fatigue (4.1 +/- 1.3,
      "a little tired, less than fresh") were within limits generally considered
      acceptable from a fatigue perspective. However, participants received 5 h or less
      sleep in the prior 24 h on 13%, were awake for at least 16 h at the end of 16%
      and worked at least 10 h on 7% of shifts. Subjects reported that they felt
      "extremely tired, very difficult to concentrate," or "completely exhausted,
      unable to function effectively" on 13% of shifts. Sleep length (OR = 0.88, p <
      0.01), shift duration (OR = 1.18, p < 0.05), night shift (REF = morning shift, OR
      = 2.12, p < 0.05) and workload ratings (OR = 1.2, p < 0.05) were significant
      predictors of ratings of extreme tiredness/exhaustion (yes/no). While on average,
      sleep loss, extended wakefulness, longer work hours and work-related fatigue do
      not appear problematic in this sample, there is still a notable percentage of
      shifts that are likely to be associated with high levels of work-related fatigue.
      Given the size of the Australian Rail Industry, with thousands of shifts
      occurring each day, this is potentially of operational concern. Further, results
      indicate that, in addition to sleep length, wakefulness and work hours, workload
      significantly influences fatigue. This has possible implications for bio
      mathematical predictions of fatigue and for fatigue management more generally.

PMID- 20691424
TI  - Improvement of angiographic findings of polypoidal choroidal vasculopathy after
      intravitreal injection of ranibizumab monthly for 3 months.
AB  - PURPOSE: To evaluate the efficacy of 1 intravitreal injection of ranibizumab
      monthly for 3 months in eyes with polypoidal choroidal vasculopathy (PCV), with
      attention to changes on indocyanine green angiography (ICGA) with confocal
      scanning laser ophthalmoscopy (cSLO). DESIGN: Prospective, consecutive case
      series. METHODS: Fifty consecutive eyes of 50 patients with symptomatic PCV who
      had not been treated previously received 1 intravitreal injection of 0.5 mg
      ranibizumab monthly for 3 months. Changes in ICGA findings with cSLO 3 months
      after the primary injection were evaluated. RESULTS: The mean visual acuity (VA)
      at baseline (0.25; range, 0.1-0.8) improved to 0.38 (P = .001) 3 months after the
      primary injection. Nineteen eyes (38%) had an improvement in VA of 0.3 or more
      logMAR unit, and 5 eyes (10%) had a decrease in VA of 0.3 or more logMAR unit.
      Polypoidal lesions disappeared on ICGA in 13 eyes (26%) and the number of lesions
      decreased but did not disappear in 26 eyes (52%), with absorption of the
      accompanying fluid on optical coherence tomography. The remaining 11 eyes (22%)
      had unchanged or worsened polypoidal lesions. A branching vascular network
      remained in all 48 eyes in which the network was detected at baseline. Although
      resolution of the branching vascular networks or decreased diameter of the
      branching vascular network occurred in 11 eyes (23%), the branching vascular
      network was unchanged or worse in 37 eyes (77%). CONCLUSION: Although a
      limitation of this study is the short-term follow-up, polypoidal lesions tended
      to respond to ranibizumab therapy, but the branching vascular network responded
      poorly.

PMID- 20691426
TI  - An experiential avoidance conceptualization of depressive rumination: three tests
      of the model.
AB  - This study examined an experiential avoidance conceptualization of depressive
      rumination in 3 ways: 1) associations among questionnaire measures of rumination,
      experiential avoidance, and fear of emotions; 2) performance on a dichotic
      listening task that highlights preferences for non-depressive material; and 3)
      psychophysiological reactivity in an avoidance paradigm modeled after the one
      used by Borkovec, Lyonfields, Wiser, and Deihl (1993) in their examination of
      worry. One hundred and thirty-eight undergraduates completed questionnaire
      measures and participated in a clinical interview to diagnose current and past
      episodes of depression. Of those, 100 were randomly assigned to a rumination or
      relaxation induction condition and participated in a dichotic listening task,
      rumination/relaxation induction, and depression induction. Questionnaire measures
      confirmed a relationship between rumination status and avoidance; however, no
      significant effects were found in the dichotic listening task.
      Psychophysiological measures indicated no difference in physiological response to
      a depression induction among high ruminators (HR). However, low ruminators (LR)
      in the relaxation condition exhibited a larger IBI response than LR in the
      rumination condition. Overall, these results provide partial support for an
      avoidance conceptualization of depressive rumination. Implications of these
      findings are discussed.

PMID- 20691428
TI  - A cis-phase interaction study of genetic variants within the MAOA gene in major
      depressive disorder.
AB  - BACKGROUND: The genetic basis of major depressive disorder (MDD) has been
      explored extensively, but the mode of transmission of the disease has yet to be
      established. To better understand the mechanism by which the monoamine oxidase A
      (MAOA) gene may play a role in developing MDD, the present work examined the cis
      phase interaction between genetic variants within the MAOA gene for the
      pathogenesis of MDD. METHODS: A variable number tandem repeat (VNTR) and 19
      single nucleotide polymorphisms (SNPs) within the gene were genotyped in 512
      unrelated patients with MDD and 567 unrelated control subjects among a Chinese
      population. Quantitative real-time polymerase chain reaction analysis was applied
      to test the effect of genetic variants on expression of the MAOA gene in MDD.
      RESULTS: Neither the VNTR polymorphism nor seven informative SNPs showed allelic
      association with MDD, but the cis-acting interactions between the VNTR
      polymorphism and four individual SNPs were strongly associated with MDD risk, of
      which the VNTR-rs1465107 combination showed the strongest association (p =
      .000011). Quantitative real-time polymerase chain reaction analysis showed that
      overall relative quantity of MAOA messenger RNA was significantly higher in
      patients with MDD than in control subjects (fold change = 5.28, p = 1.7 * 10-7)
      and that in the male subjects carrying the VNTR-L, rs1465107-A, rs6323-G,
      rs2072743-A, or rs1137070-T alleles, expression of MAOA messenger RNA was
      significantly higher in the patient group than in the control group. CONCLUSIONS:
      The cis-phase interaction between the VNTR polymorphism and functional SNPs may
      contribute to the etiology of MDD.

PMID- 20691427
TI  - Genetic associations of brain structural networks in schizophrenia: a preliminary
      study.
AB  - BACKGROUND: Schizophrenia is a complex genetic disorder, with multiple putative
      risk genes and many reports of reduced cortical gray matter. Identifying the
      genetic loci contributing to these structural alterations in schizophrenia (and
      likely also to normal structural gray matter patterns) could aid understanding of
      schizophrenia's pathophysiology. We used structural parameters as potential
      intermediate illness markers to investigate genomic factors derived from single
      nucleotide polymorphism (SNP) arrays. METHOD: We used research quality structural
      magnetic resonance imaging (sMRI) scans from European American subjects including
      33 healthy control subjects and 18 schizophrenia patients. All subjects were
      genotyped for 367 SNPs. Linked sMRI and genetic (SNP) components were extracted
      to reveal relationships between brain structure and SNPs, using parallel
      independent component analysis, a novel multivariate approach that operates
      effectively in small sample sizes. RESULTS: We identified an sMRI component that
      significantly correlated with a genetic component (r = -.536, p < .00005);
      components also distinguished groups. In the sMRI component, schizophrenia gray
      matter deficits were in brain regions consistently implicated in previous
      reports, including frontal and temporal lobes and thalamus (p < .01). These
      deficits were related to SNPs from 16 genes, several previously associated with
      schizophrenia risk and/or involved in normal central nervous system development,
      including AKT, PI3K, SLC6A4, DRD2, CHRM2, and ADORA2A. CONCLUSIONS: Despite the
      small sample size, this novel analysis method identified an sMRI component
      including brain areas previously reported to be abnormal in schizophrenia and an
      associated genetic component containing several putative schizophrenia risk
      genes. Thus, we identified multiple genes potentially underlying specific
      structural brain abnormalities in schizophrenia.

PMID- 20691430
TI  - Dissociation characteristic of the inclusion complex of cyclomaltohexaose (alpha
      cyclodextrin) with 1-methylcyclopropene in response to stepwise rising relative
      humidity.
AB  - The dissociation of a crystalline complex of cyclomaltohexaose (alpha
      cyclodextrin) and 1-methylcyclopropene has been studied in response to stepwise
      rising relative humidity at 50 degrees C using a dynamic vapor sorption
      instrument. The dissociation of the inclusion complex was monitored with a proton
      transfer reaction mass spectrometer. The increase in relative humidity generally
      triggered the complex dissociation. However, the dissociation was greatly
      retarded at 80% relative humidity, presumably owing to collapse of the
      crystalline structure. Abrupt dissociation was observed at 90% relative humidity
      which corresponded to complex dissolution. The changes in powder X-ray
      diffraction pattern of the inclusion complex during the storage period were also
      investigated.

PMID- 20691429
TI  - Clinically relevant doses of methylphenidate significantly occupy norepinephrine
      transporters in humans in vivo.
AB  - BACKGROUND: Attention-deficit/hyperactivity disorder is a psychiatric disorder
      that starts in childhood. The mechanism of action of methylphenidate, the most
      common treatment for attention deficit hyperactivity disorder, is unclear. In
      vitro, the affinity of methylphenidate for the norepinephrine transporter (NET)
      is higher than that for the dopamine transporter (DAT). The goal of this study
      was to use positron emission tomography to measure the occupancy of brain
      norepinephrine transporter by methylphenidate in vivo in humans. METHODS: We used
      (S,S)-[11C] methylreboxetine ([11C]MRB) to determine the effective dose 50 (ED50)
      of methylphenidate for NET. In a within-subject design, healthy subjects (n = 11)
      received oral, single-blind placebo and 2.5, 10, and 40 mg of methylphenidate 75
      min before [11C]MRB injection. Dynamic positron emission tomography imaging was
      performed for 2 hours with the High Resolution Research Tomograph. The
      multilinear reference tissue model with occipital cortex as the reference region
      was used to estimate binding potential non-displaceable (BP(ND)) in the thalamus
      and other NET-rich regions. RESULTS: BP(ND) was reduced by methylphenidate in a
      dose-dependent manner in thalamus and other NET-rich regions. The global ED50 was
      estimated to be .14 mg/kg; therefore, the average clinical maintenance dose of
      methylphenidate (.35-.55 mg/kg) produces 70% to 80% occupancy of NET.
      CONCLUSIONS: For the first time in humans, we demonstrate that oral
      methylphenidate significantly occupies NET at clinically relevant doses. The ED50
      is lower than that for DAT (.25 mg/kg), suggesting the potential relevance of NET
      inhibition in the therapeutic effects of methylphenidate in attention
      deficit/hyperactivity disorder.

PMID- 20691431
TI  - Synthesis of chitin cycloalkyl ester derivatives and their physical properties.
AB  - A series of acylated chitin derivatives was prepared by reacting chitin in a
      solution of trifluoroacetic anhydride and each of the cyclopropyl, cyclobutyl,
      cyclopentyl, and cyclohexyl carboxylic acids. The degree of O-acyl substitution
      was in a range of 1.1-1.4 depending upon the nature of the cyclic acid added, as
      determined by FT-IR analysis. The solubility of the products in the organic
      solvents of DMF and THF increased with an increase in the cyclic chain length of
      the carboxylic acid. Thermal gravimetric analysis indicated that the products
      were stable up to 220 degrees C for chitin cyclopropanoate and cyclobutanoate,
      and 250 degrees C for chitin cyclopentanoate and cyclohexanoate. The surface
      morphology of the products by scanning electron microscopic analysis revealed
      porous and globular surface for chitin cyclobutanoate, cyclopentanoate, and
      cyclohexanoate, contrast to the dense and smooth organization for the
      cyclopropanoate.

PMID- 20691432
TI  - 3DSDSCAR--a three dimensional structural database for sialic acid-containing
      carbohydrates through molecular dynamics simulation.
AB  - The inherent flexibility and lack of strong intramolecular interactions of
      oligosaccharides demand the use of theoretical methods for their structural
      elucidation. In spite of the developments of theoretical methods, not much
      research on glycoinformatics is done so far when compared to bioinformatics
      research on proteins and nucleic acids. We have developed three dimensional
      structural database for a sialic acid-containing carbohydrates (3DSDSCAR). This
      is an open-access database that provides 3D structural models of a given sialic
      acid-containing carbohydrate. At present, 3DSDSCAR contains 60 conformational
      models, belonging to 14 different sialic acid-containing carbohydrates, deduced
      through 10 ns molecular dynamics (MD) simulations. The database is available at
      the URL: http://www.3dsdscar.org.

PMID- 20691433
TI  - Repetitive long-term prism adaptation permanently improves the detection of
      contralesional visual stimuli in a patient with chronic neglect.
AB  - The aim of the current study was to investigate long-term effects in spatial
      awareness after daily exposure to prism adaptation during three months in a
      patient with hemispatial neglect. Results showed improvement in the detection of
      stimuli in the contralesional visual field, as measured with perimetry, in the
      contralesional visual field up to 24 months after ending prism adaptation. These
      perimetrical results suggest that compensatory eye movements are an unlikely
      candidate for an underlying mechanism.

PMID- 20691434
TI  - Thyroid-stimulating hormone receptor and thyroid hormone receptors are involved
      in human endometrial physiology.
AB  - OBJECTIVE: To study the expression, distribution, and function of thyroid
      stimulating hormone receptor (TSHR) and thyroid hormone receptors (TR) alpha1,
      alpha2, and beta1 in human endometrium. DESIGN: Experimental clinical study.
      SETTING: University hospital. PATIENT(S): 31 fertile women. INTERVENTION(S):
      Endometrial biopsy samples obtained throughout the menstrual cycle. MAIN OUTCOME
      MEASURE(S): Real-time reverse transcriptase polymerase chain reaction,
      immunohistochemistry and Western blot to study the expression of TSHR, TRalpha1,
      TRalpha2, and TRbeta1 messenger RNA (mRNA) and proteins in human endometrium.
      RESULT(S): We found TSHR, TRalpha1, TRalpha2 and TRbeta1 mRNA and proteins
      expressed in human endometrium. Immunostaining for TSHR in the luminal epithelium
      and TRalpha1 and beta1 in the glandular and luminal epithelium increased
      statistically significantly on luteinizing hormone (LH) days 6 to 9, coinciding
      with appearance of pinopodes. Endometrial stromal and Ishikawa cells expressed
      mRNA for TSHR, TR, and iodothyronine deiodinases 1-3. After 48 hours, TSH
      significantly increased leukemia inhibitory factor (LIF) and LIF receptor (LIFR)
      messenger RNA (mRNA) in endometrial stromal cells, but decreased their expression
      in Ishikawa cells. Glucose transporter 1 mRNA was up-regulated by TSH in Ishikawa
      cells. We found that TSH statistically significantly increased secretion of free
      triiodothyronine (T3) and total thyroxin (T4) by Ishikawa cells compared with
      nonstimulated cells. CONCLUSION(S): Thyroid hormones are directly involved in
      endometrial physiology.

PMID- 20691435
TI  - Efficacy of metformin therapy in adolescent girls with androgen excess: relation
      to sex hormone-binding globulin and androgen receptor polymorphisms.
AB  - We studied the effects of the SHBG (TAAAA)(n) and androgen receptor gene [AR]
      (CAG)(n) allele length on endocrine-metabolic features and body composition (by
      dual-energy X-ray absorptiometry) before and after 1 year on metformin (850 mg/d)
      in 70 girls with polycystic ovary syndrome after precocious pubarche; allele
      lengths were assessed by polymerase chain reaction in both patients and in
      population control subjects (n = 107). Longer SHBG (TAAAA)(n) alleles (>8
      repeats) were associated with more improvement of the lipid profile after 1 year
      on metformin, whereas longer AR (CAG)(n) alleles were related to more
      normalization of the androgen and lipid levels after therapy; longer alleles in
      both genes had an additive effect on the beneficial changes of SHBG, T, and
      lipids after metformin.

PMID- 20691436
TI  - Improving of pregnancy rate by modifying embryo transfer technique.

PMID- 20691437
TI  - Ongoing pregnancy after human menopausal gonadotropin stimulation and timed
      intercourse in a 40-year-old woman with undetectable antimullerian hormone
      levels.

PMID- 20691440
TI  - No effect of dynamic loading on bone graft healing in femoral segmental defect
      reconstructions in the goat.
AB  - We studied if a static or dynamic mode of nail fixation influenced the healing of
      segmental defect reconstructions in long bones. Defects in the femur of goats
      were reconstructed using a cage filled with firmly impacted morsellised allograft
      mixed with a hydroxyapatite paste (Ostim). All reconstructions were stabilised
      with an intramedullary nail. In one group (n=6) the intramedullary nail was
      statically locked, in the second group (n=6) a dynamic mode of nail fixation was
      applied. We hypothesised that dynamisation of the nail would load, and by that
      stimulate the healing of the bone graft. Mechanical torsion strength of the
      reconstructions of the femur with the static and dynamic mode of nail fixation
      appeared to be 74.8+/-17.5% and 73.0+/-13.4%, respectively as compared with the
      contralateral femurs after 6 months. In all reconstructions, the grafts united
      radiographically and histologically to the host bone, and remodelled into a new
      vital bone structure. No large differences were found between newly formed bone
      areas inside and outside the mesh of the two groups. The area of callus outside
      the mesh in the dynamic mode of fixation group was smaller (p=0.042), whilst the
      percentage of bone outside the mesh was larger (p=0.049), as compared to the
      static mode of fixation group. The data suggest that healing of these defects
      with impacted morsellised graft in a cage is not significantly influenced by the
      mode of fixation of the nail in this model.

PMID- 20691441
TI  - Should unstable extra-articular distal radial fractures be treated with fixed
      angle volar-locked plates or percutaneous Kirschner wires? A prospective
      randomised controlled trial.
AB  - Fractures of the distal radius are commonly treated with cast immobilisation;
      however, those potentially unstable injuries with dorsal comminution may need
      operative intervention. This intervention is usually with manipulation and
      Kirschner wires but advances in locking-plate technology have enabled surgeons to
      achieve anatomical reconstruction of complex fracture patterns, even in poor
      quality osteoporotic bone.To ascertain if fixed-angle volar-locked plates confer
      a significant benefit over manipulation and Kirschner-wire stabilisation, we
      prospectively randomised 56 adult patients with isolated, closed,unilateral,
      unstable extra-articular fractures into two treatment groups, one fixed with K
      wires and the other fixed with a volar locking plate.Functional outcomes were
      assessed using Gartland and Werley and Disabilities of the Arm, Shoulder and Hand
      (DASH) scores. These were statistically better in the plate group at 3 and 6
      months.Radiological assessment showed statistically better results at 6 weeks, 3
      months and 6 months, postoperatively.In the plate group, there was no significant
      loss of fracture reduction.

PMID- 20691442
TI  - Full body radiography (LODOX-Statscan) as a screening device for maxillofacial
      injuries, where CT scanning is not immediately available.

PMID- 20691443
TI  - On admission haemoglobin in patients with hip fracture.
AB  - Several authors have identified on admission haemoglobin level as the most useful
      predictor of transfusion risk in patients with a hip fracture. A low
      postoperative haemoglobin unexplained by perioperative blood loss is not uncommon
      in these patients. The drop in haemoglobin after re-hydration prior to surgery
      should depend not only on the degree of dehydration but also on the amount of
      blood lost in the fracture.We could find no study in the English literature
      estimating the magnitude of this fall in haemoglobin after re-hydration prior to
      surgery.We conducted a prospective study to estimate the magnitude of fall in
      haemoglobin after rehydration prior to surgery by repeating the full blood count
      after at least 12 h of preoperative fluid resuscitation in 127 patients with hip
      fracture (75 consecutive at one centre and 52 consecutive at another).The average
      preoperative drop in haemoglobin was 2.23 gram/decilitre (g/dL) (p-value = 0.00)
      in subtrochanteric fractures, 1.1 g/dL (p-value = 0.001) in intertrochanteric
      fractures and 0.7 g/dL (p-value = 0.02) in intracapsular fractures. Fifteen
      patients with a haemoglobin level >9 g/dL on admission were found to have a
      haemoglobin level <9 g/dL on repeat test and were prevented from going to theatre
      without arrangements for perioperative transfusion during this study. Their
      predicted average postoperative haemoglobin without perioperative blood
      transfusion was calculated to be 6.5 g/dL.The on admission haemoglobin level was
      found to be falsely reassuring and could lead to a very low postoperative
      haemoglobin level. This could prove to be dangerous for many patients especially
      if remains undetected for several hours. We recommend that all patients with
      subtrochanteric fractures,and all patients with intertrochanteric or
      intracapsular fractures with a haemoglobin of less than 12 g/dL on admission have
      a repeat haemoglobin level performed prior to their surgery.

PMID- 20691444
TI  - Temporary intra-operative reduction techniques for tibial fracture fixation: A
      review of the literature.
AB  - Accurate intra-operative reduction and maintenance of reduction is essential for
      successful fixation of tibial fractures. Although many tibial fractures can be
      reduced with minimal manipulation, numerous techniques have been described to
      facilitate fixation of more difficult fractures. These include use of a traction
      table, manual traction techniques, temporary distracters, reduction clamps and
      temporary unicortical plating. This article reviews the literature and assesses
      the options available for the temporary reduction and maintenance of reduction of
      tibial fractures prior to definitive fixation.

PMID- 20691445
TI  - Term labor management and outcomes in treated HIV-infected women without
      contraindications to vaginal delivery and matched controls.
AB  - OBJECTIVE: To assess labor management and outcomes for treated HIV-infected
      pregnant women with no obstetric or virologic contraindications to vaginal
      delivery. METHOD: A retrospective case-control study was conducted at a single
      center with 146 treated HIV-infected pregnant women without obstetric or
      virologic contraindications to vaginal delivery and 146 controls. Cases and
      controls were matched for parity, previous cesarean delivery, and geographic
      origin. RESULTS: The mode of delivery was similar in the 2 groups but the
      episiotomy rate was significantly lower among the HIV-infected women (29.6% vs
      45.6%, P = 0.01), with no difference in mean birth weight, simple or complex
      perineal laceration rates or neonatal outcome. Postpartum morbidity was also
      similar for controls and HIV-infected women with a CD4(+) cell count of 200
      cells/mL or higher. However, in the study group, postpartum morbidity was higher
      among those whose CD4(+) cell count was lower than this threshold (3.2% vs 22.2%,
      P = 0.007). No case of mother-to-child transmission of HIV occurred. CONCLUSION:
      HIV-infected women with no contraindication to vaginal delivery seem to have the
      same labor outcomes as uninfected women.

PMID- 20691446
TI  - Platelet gene polymorphisms and risk of bleeding in patients undergoing elective
      coronary angiography: a genetic substudy of the PRAGUE-8 trial.
AB  - AIM: Utilization of cardiac catheterization has increased dramatically over time.
      Bleeding is a major prognostic predictor after percutaneous coronary
      catheterization procedures. This study aimed to assess the impact of eight
      polymorphisms of genes encoding platelet receptors and enzymes on the risk of
      bleeding in patients undergoing elective coronary angiography (CAG). METHODS:
      Polymorphisms of platelet receptors, GP Ia (807C>T, rs1126643), GP VI (13254T>C,
      rs1613662), GP IIIa (HPA-1, rs5918), PAR-1 (IVS-14A>T, rs168753), P2Y(12) (34C>T,
      rs6785930 and H1/H2 haplotype, rs2046934), and genetic variations of the gene
      coding for cyclooxygenase-1 (COX-1) (-842A>G, rs10306114 and 50C>T, rs3842787)
      were studied. The frequencies of gene polymorphisms carriers were investigated in
      696 patients undergoing elective CAG because of suspected or proven stable
      coronary artery disease. Genotyping was done using PCR, followed by melting curve
      analysis with specific fluorescent hybridization probes. RESULTS: In patients
      undergoing elective CAG (without ad hoc percutaneous coronary intervention (PCI)
      and without clopidogrel pretreatment) a significant association was found between
      bleeding risk and variations in the gene coding for COX-1 (-842A>G and 50C>T)
      (both p=0.013). Six other investigated polymorphisms did not show any influence
      on bleeding complications. After controlling for potential bleeding confounders,
      the association between COX-1 gene polymorphisms (-842A>G and 50C>T) and bleeding
      risk remained statistically significant (both odds ratios 12.1, p=0.012).
      CONCLUSION: Cyclooxygenase-1 -842G and 50T alleles significantly contribute to
      the risk of bleeding complications in patients undergoing elective CAG. Genetic
      testing is able to influence the safety of diagnostic cardiac catheterization in
      large numbers of low risk patients with borderline indications.

PMID- 20691447
TI  - Parental consanguinity and family history of coronary artery disease strongly
      predict early stenosis.
AB  - BACKGROUND: Coronary artery disease (CAD) is a multifactorial disease with
      acquired and inherited components. AIM: We investigated the roles of family
      history and consanguinity on CAD risk and age at diagnosis in 4284 patients. The
      compounded impact of diabetes, hyperlipidemia, hypertension, smoking, and BMI,
      which are known CAD risk factors, on CAD risk and age at diagnosis was also
      explored. METHODS: CAD was determined by cardiac catheterization. Logistic
      regression and stratification were performed to determine the impact of family
      history and consanguinity on risk and onset of CAD, controlling for diabetes,
      hyperlipidemia, hypertension, smoking, and BMI. RESULTS: Family history of CAD
      and gender significantly increased the risk for young age at diagnosis of CAD
      (p<0.001). Consanguinity did not promote risk of CAD (p=0.38), but did affect age
      of disease diagnosis (p<0.001). The mean age at disease diagnosis was lowest,
      54.8 years, when both family history of CAD and consanguinity were considered as
      unique risk factors for CAD, compared to 62.8 years for the no-risk-factor
      patient category (p<0.001). CONCLUSIONS: Family history of CAD and smoking are
      strongly associated with young age at diagnosis. Furthermore, parental
      consanguinity in the presence of family history lowers the age of disease
      diagnosis significantly for CAD, emphasizing the role of strong genetic and
      cultural CAD modifiers. These findings highlight the increased role of genetic
      determinants of CAD in some population subgroups, and suggest that populations
      and family structure influence genetic heterogeneity between patients with CAD.

PMID- 20691448
TI  - Retention of structurally diverse drugs in human serum albumin chromatography and
      its potential to simulate plasma protein binding.
AB  - The retention behavior of 39 structurally diverse neutral, basic and acidic drugs
      was investigated on an HSA stationary phase using PBS buffer (pH 7.0) and
      acetonitrile or 2-propanol as organic modifiers. Extrapolated or directly
      measured logk(w) values as well as isocratic retention factors were correlated
      with plasma protein binding data taken from the literature. Retention factors
      determined in the presence of 10% acetonitrile led to high quality 1:1
      correlation with apparent logK(HSA) values. The derived reference equation was
      successfully validated using a secondary set of 24 drugs. Further analysis of HSA
      retention into more fundamental properties revealed the involvement of anionic
      species in solute-stationary phase interactions, expressed by the negatively
      charged fraction, besides the partitioning mechanism which was reflected by
      lipophilicity. Protonation of basic drugs, although less important, may also
      influence retention, leading to reduced partitioning into the HSA surface as a
      net effect, while it seems to have no effect on HSA binding. The above results
      were further confirmed by linear solvation energy relationships (LSER).

PMID- 20691449
TI  - Profiling food volatiles by comprehensive two-dimensional ga schromatography
      coupled with mass spectrometry: advanced fingerprinting approaches for
      comparative analysis of the volatile fraction of roasted hazelnuts (Corylus
      avellana L.) from different origins.
AB  - This study examined how advanced fingerprinting methods (i.e., non-targeted
      methods) provide reliable and specific information about groups of samples based
      on their component distribution on the GC x GC chromatographic plane. The
      volatile fractions of roasted hazelnuts (Corylus avellana L.) from nine different
      geographical origins, comparably roasted for desirable flavor and texture, were
      sampled by headspace-solid phase micro extraction (HS-SPME) and then analyzed by
      GC x GC-qMS. The resulting patterns were processed by: (a) "chromatographic
      fingerprinting", i.e., a pattern recognition procedure based on retention-time
      criteria, where peaks correspondences were established through a comprehensive
      peak pattern covering the chromatographic plane; and (b) "comprehensive template
      matching" with reliable peak matching, where peak correspondences were
      constrained by retention time and MS fragmentation pattern similarity criteria.
      Fingerprinting results showed how the discrimination potential of GC x GC can be
      increased by including in sample comparisons and correlations all the detected
      components and, in addition, provide reliable results in a comparative analysis
      by locating compounds with a significant role. Results were completed by a
      chemical speciation of volatiles and sample profiling was extended to known
      markers whose distribution can be correlated to sensory properties, geographical
      origin, or the effect of thermal treatment on different classes of compounds. The
      comprehensive approach for data interpretation here proposed may be useful to
      assess product specificity and quality, through measurable parameters strictly
      and consistently correlated to sensory properties and origin.

PMID- 20691450
TI  - Effects of redox conditions and zinc(II) ions on metallothionein aggregation
      revealed by chip capillary electrophoresis.
AB  - Metallothioneins (MTs) belong to cysteine-rich proteins with unique higher
      structure. One of the most known MT's functions is metals detoxification and
      maintaining their homeostasis in a cell. Structure of MT with naturally occurred
      zinc(II) ions can be affected by concentration of metal ions as well as redox
      milieu inside a cell, however the exact explanation and biochemical effects of
      the structural changes are still missing. In this study we used capillary
      electrophoresis on chip coupled with fluorescence detection to determine
      structural changes of MT with increasing concentration of zinc(II) ions and under
      various redox conditions. To investigate the structural-dependent effects,
      reduced and/or oxidized apo-MT (MT without natural occurred metal ion) was
      prepared. Zinc binding into reduced and/or oxidized apo-MT was compared. MT was
      incubated with 0, 5, 15, 25, 50 and 100 MUM ZnCl(2) for 1h in 37 degrees C.
      Formation of MT aggregates with increasing zinc concentration was observed by
      spectrophotometry, chip capillary electrophoresis, and SDS-PAGE. We found out
      that reduced MT forms aggregates more readily compared to oxidized MT. Using the
      chip capillary electrophoresis allowed us relative quantification of MT
      aggregation as a decrease in the area of the signal corresponding to the monomer
      form of MT (Mw 15 kDa, migration time 26.5s) and its ratio to total signal (sum
      of all signals measured by the electrophoresis). The dependences had an
      exponential character with equation y=2.4*e(-0.01x), R(2)=0.945 for 15 kDa peak
      area and y=0.11 * e(-0.01x), R(2)=0.938 for decrease of 15 kDa peak area ratio to
      the total signal. Zn-MT interaction was 30% faster during the first 15 min and
      50% faster during the whole experiment for reduced MT. It can be concluded that
      formation of MT aggregates is dependent on redox state and Zn(II) concentration.

PMID- 20691451
TI  - Effect of sphingosine on domain morphology in giant vesicles.
AB  - Sphingosine is a bioactive molecule which is known to participate in the
      regulation of a number of cellular processes such as apoptosis, cell
      differentiation, growth, etc. Sphingosine was observed to exhibit different
      domain morphology depending on the surrounding lipid matrix in biomimetic systems
      such as giant vesicles. Our current results showed that in a glycerophospholipid
      matrix sphingosine segregated in gel leaf-like domains whereas cholesterol
      presence increased its miscibility by melting gel domains in a concentration
      dependent manner. Sphingosine and cholesterol did not form merging liquid domains
      on the micron scale as observed for sphingomyelin and cholesterol. However, we
      were able to visualize that sphingosine appears as a stabilizer and amplifier of
      domains in liquid-ordered phase by increasing the temperature of their formation
      and fraction. These results imply that sphingosine acts as a modulator of the
      lipid domain formation and thus it could exert its biological role, not only
      through direct binding to proteins, but also indirectly by influencing their
      sorting in membranes and modulating the processes of signal transduction.

PMID- 20691452
TI  - Immobilization of galactose ligands on thermoresponsive culture surface and its
      influence on cell adhesion/detachment.
AB  - A novel bio-functionalized thermoresponsive surface was prepared by UV-induced
      copolymerization of N-isopropylacrylamide (NIPAAm) and acrylic acid (AAc) and
      grafting onto tissue culture polystyrene (TCPS) dishes, followed by
      immobilization of galactose ligands. The results indicated that the roughness of
      surfaces was increased after copolymerization with NIPAAm and immobilization of
      galactose ligands. The amount of monomers grafted on TCPS was increased with
      increasing photografting time. The temperature sensitivity of surface was
      improved with increasing amount of NIPAAm grafted on TCPS, and surface
      hydrophilicity was enhanced by the introduction of carboxyl groups and galactose
      ligands, which accelerated cell detachment. Adhesion, proliferation, detachment
      and transshipment of human hepatoma cell line (HepG2) on the modified surfaces
      were examined. The immobilization of galactose ligands facilitated the cell
      adhesion and proliferation. HepG2 cells growing on the modified surfaces could be
      recovered spontaneously by only reducing culture temperature. The activity of
      cells obtained by temperature induction was higher than that obtained by
      enzymatic digestion.

PMID- 20691453
TI  - Kinetics of heterogeneous nucleation on a rough surface: nucleation of a liquid
      phase in nanocavities.
AB  - The kinetic theory of heterogeneous nucleation of a liquid developed by
      Nowakowski and Ruckenstein [J. Phys. Chem. 96 (1992) 2313] for a planar surface
      is extended to the nucleation of liquid clusters in spherical nanocavities of a
      solid surface. It is shown that for all considered contact angles and radii of
      the cavity, the nucleation rate is higher than that on a planar surface and that
      it increases with increasing strength of the fluid-solid interactions. The
      difference is small at high supersaturations (small critical clusters), but is
      orders of magnitude higher at lower supersaturations when the cluster has a size
      comparable with the size of the cavity. At constant contact angle the nucleation
      rate increases with increasing curvature of the cavity. The dependence of the
      nucleation rate on the contact angle is not monotonous.

PMID- 20691454
TI  - A hospital-based intermittent nocturnal hemodialysis program for children and
      adolescents.
AB  - OBJECTIVE: To establish a hospital-based nocturnal hemodialysis (NHD) program for
      children and adolescents. STUDY DESIGN: Sixteen patients (age, 0.5 to 17 years)
      were prospectively included. Uremia-associated measures as well as amount and
      dosage of medication were enumerated. Quality of life also was evaluated. Results
      were compared with data of the same patients on conventional hemodialysis and
      with matched control subjects (conventional HD). RESULTS: NHD was well tolerated.
      Median Kt/V values increased. Predialytic mean arterial pressure, urea,
      phosphate, and parathyroid hormone levels decreased. There was an increase in
      protein catabolic rate. Dietary and fluid restrictions could be lifted. Amount
      and dosage of phosphate and potassium binders and antihypertensive medication
      could be reduced. Quality of life improved and days of absence from school
      decreased in all patients. CONCLUSIONS: In addition to a better control of uremia
      associated measures, NHD allows free dietary and fluid intake and improves
      patient well-being. Given the continuing shortage of donor organs for kidney
      transplantation and the high morbidity and mortality on conventional HD,
      intensified dialysis regimens are a much-needed therapeutic option.

PMID- 20691456
TI  - An unusual lanostane-type triterpenoid, spiroinonotsuoxodiol, and other
      triterpenoids from Inonotus obliquus.
AB  - An unusual lanostane-type triterpenoid, spiroinonotsuoxodiol (1), and two
      lanostane-type triterpenoids, inonotsudiol A (2) and inonotsuoxodiol A (3), were
      isolated from the sclerotia of Inonotus obliquus. Their structures were
      determined to be (3S,7S,9R)-3,7-dihydroxy-7(8-->9)abeo-lanost-24-en-8-one (1),
      lanosta-8,24-dien-3beta,11beta-diol (2), and (22R)-3beta,22-dihydroxylanosta-8,24
      dien-11-one (3) on the basis of NMR spectroscopy, including 1D and 2D ((1)H-(1)H
      COSY, NOESY, HMQC, HMBC) NMR, and FABMS. Compounds 1-3 showed moderate activity
      against cultured P388, L1210, HL-60 and KB cells.

PMID- 20691455
TI  - Correlation between serum caffeine levels and changes in cytokine profile in a
      cohort of preterm infants.
AB  - OBJECTIVE: To determine changes in cytokine levels associated with caffeine
      treatment in a cohort of preterm infants. STUDY DESIGN: For this observational
      prospective study, we collected clinical data from 26 preterm infants (<= 30
      weeks gestational age). In addition to caffeine levels, cytokine profiles in
      peripheral blood (PB) and tracheal aspirates (TA) were determined with enzyme
      linked immunosorbent assay at birth, before and after (at 24 hours and 1 week)
      initiation of caffeine. Non-parametric statistics were applied. RESULTS: Included
      infants were 26.9 +/- 1.7 weeks gestational age and weighed 985 +/- 202 g. At
      birth, all cytokine concentrations were significantly greater in TA than PB.
      Serum caffeine levels were 11.1 MUg/mL (interquartile range, 1.85) at
      approximately 24 hours post-load and 16.4 (8.7) MUg/mL at 1 week on treatment. At
      approximately 24 hours post-load, interleukin (IL)-10 levels decreased by 47.5%
      (P = .01) in PB and 38.5% (P = .03) in TA, whereas other cytokine levels remained
      unchanged. At 1 week, caffeine levels were correlated (U-shaped) with changes in
      proinflammatory tumor necrosis factor-alpha (R(2) = 0.65; P = .0008), interleukin
      (IL)-1beta (R(2) = 0.73; P = .0007), and IL-6 (R(2) = 0.59; P = .003), whereas
      inversely correlated (linear) with the anti-inflammatory IL-10 (R(2) = 0.64; P =
      .0008). Altogether, caffeine, at serum levels >= 20 MUg/mL, was associated with a
      proinflammatory profile after 1 week of treatment. CONCLUSIONS: Caffeine
      treatment for apnea of prematurity correlates with changes in cytokine profile.
      Caffeine levels >= 20 MUg/mL are associated with a proinflammatory profile in our
      cohort of preterm infants.

PMID- 20691457
TI  - Agreement among multiple measures of self-reported smoking status in Chinese
      urban residents.
AB  - OBJECTIVE: To compare five alternative self-report methods for assessing the
      smoking status of Chinese urban residents, and to estimate their reliability or
      agreement. STUDY DESIGN: Cross-sectional survey with multistage sampling.
      METHODS: Cross-sectional survey data were collected from residents in two Chinese
      cities, and the prevalence of smoking and smoking frequency were estimated by
      means of six methods of self-report labelled SMD, SM1, SM6, SMF, SMC and SM. SM,
      the method of smoking assessment endorsed by the World Health Organisation (WHO),
      served as a referent in estimating agreement among the domestic methods. Cohen's
      kappa measured overall intermethod agreement. RESULTS: Data on 1167 eligible
      respondents were analysed. kappa values ranged from 0.79 to 0.89 for current
      smoking, from 0.84 to 0.94 for daily smoking, and from 0.23 to 0.62 for
      occasional smoking. Compared with the referent (SM, 61%), SMD (53%), SM1 (57%),
      SM6 (54%) and SMC (55%) significantly understated the prevalence of current
      smoking among Chinese urban residents. SM1 (11%), SM6 (10%), SMD (6%) and SMC
      (6%) significantly understated the prevalence of occasional smoking compared with
      the refererent (SM, 14%). No variation emerged in prevalence estimates of daily
      smoking. CONCLUSIONS: Despite some variability, the five domestic methods used to
      assess smoking status in China generally produced similar results to those based
      on SM, the method advocated by WHO. Discrepancies between domestic assessment
      methods peaked in estimating the prevalence of occasional smoking.

PMID- 20691458
TI  - [Guidelines for the diagnosis and treatment of cutaneous squamous cell carcinoma
      and precursor lesions. Guidelines].

PMID- 20691459
TI  - Mechanisms of arsenic enrichment in geothermal and petroleum reservoirs fluids in
      Mexico.
AB  - The lack of chemical similarity between thermal fluids in geothermal and
      petroleum reservoirs in Mexico indicates a distinct origin for arsenic in both
      types of reservoirs. Deep fluids from geothermal reservoirs along the
      Transmexican Volcanic Belt (TMVB) are characterized by elevated arsenic
      concentrations, within a range between 1 and 100 mg L(-1) at a depth from 600 to
      3000 m b.s.l. Based on hierarchical cluster analysis (HCA), arsenic is linked to
      typical geothermal species like lithium, silica, and boron. The lack of
      correlation between arsenic and salinity reflects the importance of secondary
      water-rock interaction processes. The predominance of arsenic compared to Fe- and
      Cu-concentrations, and the occurrence of secondary minerals (sulfides and clay
      minerals) in temperature-dependent hydrothermal zones, supports this hypothesis.
      Neither magmatic fluids input, nor As mineralization is a prerequisite for As
      enrichment in Mexican geothermal fluids. In contrast, petroleum reservoir waters
      from sedimentary basins in SE-Mexico show maximum As concentrations of 2 mg L(
      1), at depths from 2900 to 6100 m b.s.l. The linear chloride-arsenic correlation
      indicates that evaporated seawater represents the major source for aqueous
      arsenic in oil reservoirs, and only minor arsenic proportions are derived from
      interaction with carbonate host rock. Speciation modeling suggests the lack of
      arsenic solubility control in both geothermal and petroleum reservoirs, but
      precipitation/co-precipitation of As with secondary sulfides could occur in
      petroleum reservoirs with high iron concentrations. Geothermal fluids from
      magmatic-type reservoirs (Los Azufres and Los Humeros at the TMVB and Las Tres
      Virgenes with a granodioritic basement) show relative constant arsenic
      concentrations through varying temperature conditions, which indicates that
      temperatures above 230-250  degrees C provide optimal and stable conditions for
      arsenic mobility. In contrast, temperature conditions for sedimentary-type
      reservoirs are irrelevant for water-rock interaction processes, as suggested by
      low arsenic aqueous concentration for both Cerro Prieto geothermal fluids (high
      temperature - sedimentary type) and oil field formation water (low temperature -
      sedimentary type).

PMID- 20691460
TI  - Enhanced electrokinetic treatment of marine sediments contaminated by heavy
      metals and PAHs.
AB  - Dredged sediments contaminated by heavy metals and PAHs were subjected to both
      unenhanced and enhanced electrokinetic remediation under different operating
      conditions, obtained by varying the applied voltage and the type of conditioning
      agent used at the electrode compartments in individual experiments. While metals
      were not appreciably mobilized as a result of the unenhanced process, metal
      removal was found to be significantly improved when both the anodic and cathodic
      reservoirs were conditioned with the chelating agent EDTA, with removal yields
      ranging from 28% to 84% depending on the contaminant concerned. As for the effect
      on organic contaminants, under the conditions tested the electrokinetic treatment
      displayed a poor removal capacity towards PAHs, even when a surfactant (Tween 80)
      was used to promote contaminant mobilization, indicating the need for further
      investigation on this issue. Further research on organics removal from this type
      of materials through electrokinetic remediation is thus required. Furthermore, a
      number of technical and environmental issues will also require a careful
      evaluation with a view to full-scale implementation of electrokinetic sediment
      remediation. These include controlling side effects during the treatment (such as
      anodic precipitation, oxidation of the conditioning agent, and evolution of toxic
      gases), as well as evaluating the potential ecotoxicological effects of the
      chemical agents used.

PMID- 20691461
TI  - Genotoxic analysis in aquatic environment under influence of cyanobacteria, metal
      and radioactivity.
AB  - The micronucleus (MN) and nuclear abnormality (NA) tests were employed to
      evaluate the genotoxic potential of the Lucrecia dam (RN, Brazil) located in a
      semi-arid region and influenced by crop irrigation and irregular rainfall. The
      analyses of these water samples demonstrated the presence of several
      cyanobacteria as well as metals and radioactivity. The Nile Tilapia (Oreochromis
      niloticus) was used for micronucleus and nuclear abnormality assays and analysis
      of metal concentrations in gills and liver samples. Genotoxic assays in source
      water fish showed a significant increase in the frequency of nuclear damage (MN
      and NA) in relation to the negative control group. In conclusion, the results
      obtained with water surface and biological samples from the Lucrecia dam suggest
      that this important water resource contains a number of chemical and
      microbiological pollutants with genotoxic potential and that these substances may
      be compromising the species inhabiting this ecosystem. Particular care must be
      taken to prevent further degradation of this water supply. Capsule: A battery of
      assay was successfully applied to assess the water quality of Lucrecia dam from a
      Northeastern region of Brazil.

PMID- 20691462
TI  - Effect of landfill characteristics on leachate organic matter properties and
      coagulation treatability.
AB  - This work spans landfill characteristics, leachate organic matter properties, and
      coagulation chemistry to provide new insights into the physical-chemical
      treatability of stabilized landfill leachate. Furthermore, leachate organic
      matter is viewed in terms of dissolved organic matter (DOM) present in the
      natural environment, and coagulation chemistry is evaluated based on previous
      leachate and water treatment coagulation studies. Stabilized leachate was
      collected from four landfills for a total of seven leachate samples, and samples
      were coagulated using ferric chloride, ferric sulfate, and aluminum sulfate.
      Landfill characteristics, such as age, leachate recirculation, and cover
      material, influenced properties of DOM present in the leachate, as measured by
      specific ultraviolet (UV) absorbance at 254 nm (SUVA254) and fluorescence
      excitation-emission matrices. The coagulation performance of the metal salts was
      ferric sulfate>aluminum sulfate>ferric chloride, and DOM removal followed the
      trend of color>UV254>dissolved organic carbon>chemical oxygen demand (COD).
      Finally, a strong association was found between increasing SUVA254 and increasing
      DOM removal for coagulation of both leachate and natural surface water. Thus,
      SUVA254 is expected to be a better predictor of leachate treatability, in
      particular DOM removal, than the traditionally used ratio of biochemical oxygen
      demand to COD.

PMID- 20691463
TI  - Estimating nutrient releases from agriculture in China: an extended substance
      flow analysis framework and a modeling tool.
AB  - Agriculture related pollution has attracted the attention of policy makers as
      well as scientists in China as its contribution to water impairment has
      increased, and quantitative information at the national and regional levels is
      being sought to support decision making. However, traditional approaches are
      either time-consuming, expensive (e.g. national surveys) or oversimplified and
      crude (e.g. coefficient methods). Therefore, this study proposed an extended
      substance flow analysis (SFA) framework to estimate nutrient releases from
      agricultural and rural activities in China by depicting the nutrient flows in
      Chinese agro-ecosystems. The six-step process proposed herein includes: (a)
      system definition; (b) model development; (c) database development; (d) model
      validation; (e) results interpretation; and (f) uncertainty analysis. The
      developed Eubolism (Elementary Unit based nutrient Balance mOdeLIng in agro
      ecoSysteM) model combined a nutrient balance module with an emission inventory
      module to quantify the nutrient flows in the agro-ecosystem. The model was
      validated and then applied to estimate the total agricultural nutrient loads,
      identify the contribution of different agricultural and rural activities and
      different land use types to the total loads, and analyze the spatial pattern of
      agricultural nutrient emissions in China. These results could provide an entire
      picture of agricultural pollution at the national level and be used to support
      policy making. Furthermore, uncertainties associated with the structure of the
      elementary units, spatial resolution, and inputs/parameters were also analyzed to
      evaluate the robustness of the model results.

PMID- 20691464
TI  - Change in International Prostate Symptom storage subscore after long-term medical
      therapy in BPH patients: finasteride and alpha-blocker combination therapy in men
      with moderate-to-severe LUTS/BPH in Korea.
AB  - OBJECTIVE: To evaluate the efficacy and the change of International Prostate
      Symptom Score (IPSS) storage subscore after combination therapy (alpha-blocker
      and finasteride) in patients with lower urinary tract symptoms (LUTS) consistent
      with moderate-to-severe benign prostatic hyperplasia (BPH) and compared with
      alpha-blocker-only treatment. METHODS: A total of 1315 patients seen in 5 urology
      centers in Korea from January 2001 to August 2007, with LUTS secondary to BPH
      were enrolled. Patients were divided into 4 groups according to treatment pattern
      (alpha-blocker monotherapy vs combination therapy) and IPSS storage subscores
      (>=6 vs <6). The changes from baseline in prostate volume, prostate-specific
      antigen concentration, IPSS, and Q(max.) were analyzed. We also determined the
      statistical differences among 4 groups in the IPSS, Q(max.), quality of life
      score (QoL), and prostate volume. RESULTS: Of the 1315 men, 217 (16.5%) completed
      the month 48 visit. All groups showed significant improvements in the IPSS total
      score, IPSS voiding subscores, and QoL at 1 year. However, the high storage
      subscore group at baseline showed a significantly higher improvement in IPSS
      total scores and IPSS voiding subscores compared with the low storage subscore
      group at year 4. IPSS storage subscores were improved only in patients with high
      storage subscores at baseline, especially in combination treatment group. The
      mean change in QoL score from baseline to year 4 was significantly improved in
      high storage subscore groups. CONCLUSIONS: Data from this retrospective analysis
      suggest that long-term combination treatment would be beneficial, especially to
      patients with severe storage symptoms at baseline.

PMID- 20691465
TI  - Prognostic determinants in patients with stage IIIC and IV uterine papillary
      serous carcinoma.
AB  - OBJECTIVE: The aim of this study was to evaluate the survival impact of
      cytoreductive surgery and other prognostic determinants in patients with stage
      IIIC and IV uterine papillary serous carcinoma (UPSC). METHODS: All patients with
      FIGO stage IIIC and IV UPSC who underwent surgical staging at the two
      participating institutions, between January 1, 1995 and December 31, 2007, were
      identified from the tumor registry database. The Kaplan-Meier method was used to
      generate overall survival (OS) data. Factors predictive of outcome were compared
      using the log-rank test and Cox regression analysis. RESULTS: Analysis of 79
      patients with stage IIIC-IV disease was performed. Optimal cytoreduction was
      associated with a median survival of 36 months, compared with 12 months for
      patients who underwent a suboptimal surgical effort (p=0.001), and a disease-free
      survival (DFS) of 21 months vs. 10 months (p=0.001), respectively. Regression
      analysis identified stage (HR=2.4, p=0.03), absence of visible residual disease
      (HR=0.5, p=0.03), and chemotherapy (HR=0.1, p<0.001) as independent predictors of
      OS. CONCLUSIONS: Cytoreduction to no gross residual disease and the use of
      platinum therapy are associated with a significant survival benefit for patients
      with stage IIIC-IV UPSC. Recommended management for this group of patients should
      consist of maximal surgical cytoreduction followed by platinum-based
      chemotherapy, preferably in combination with paclitaxel. Adjuvant radiation
      therapy should also be considered.

PMID- 20691466
TI  - A shaker K+ channel with a miniature engineered voltage sensor.
AB  - Voltage-gated ion channels sense transmembrane voltage changes via a paddle
      shaped motif that includes the C-terminal part of the third transmembrane segment
      (S3b) and the N-terminal part of the fourth segment ((NT)S4) that harbors voltage
      sensing arginines. Here, we find that residue triplets in S3b and (NT)S4 can be
      deleted individually, or even in some combinations, without compromising the
      channels' basic voltage-gating capability. Thus, a high degree of complementarity
      between these S3b and (NT)S4 regions is not required for basic voltage gating per
      se. Remarkably, the voltage-gated Shaker K(+) channel remains voltage gated after
      a 43 residue paddle sequence is replaced by a glycine triplet. Therefore, the
      paddle motif comprises a minimal core that suffices to confer voltage gating in
      the physiological voltage range, and a larger, modulatory part. Our study also
      shows that the hydrophobic residues between the voltage-sensing arginines help
      set the sensor's characteristic chemical equilibrium between activated and
      deactivated states.

PMID- 20691467
TI  - Bovine ovarian follicular cysts: in vitro effects of lecirelin, a GnRH analogue.
AB  - This study investigates the mechanisms of action by which a GnRH analogue may
      modulate the contractility of the bovine ovarian follicular wall. The in vitro
      evaluation of the spontaneous basal contractility of bovine preovulatory and
      cystic follicles was performed, followed by testing the effects of lecirelin, a
      GnRH analogue, on their basal contractility. Strips of tissue in isolated organ
      bath were employed. In addition, to better investigate the mechanism of action of
      lecirelin, the study of the effects of cumulative doses of nifedipine (a calcium
      channel blocker), phentolamine (an alpha-adrenoceptor antagonist) and reserpine
      (an inhibitor of the vesicular up-take of catecholamines) alone and, at the
      highest doses employed, associated to lecirelin, was set up. The results
      demonstrate that in basal conditions and after the addition of lecirelin, the
      strips from preovulatory follicles contract significantly more than strips from
      cysts. Furthermore, among the patterns of contractility evoked by the three drugs
      employed, the one induced by nifedipine was the only one unaffected by the
      addition of lecirelin. The data obtained provide the hypothesis that one of the
      main mechanisms of action of GnRH, could involve calcium channels.

PMID- 20691468
TI  - Gestational weight gain and birthweight.

PMID- 20691469
TI  - The association between pregnancy weight gain and birthweight: a within-family
      comparison.
AB  - BACKGROUND: Excessive weight gain during pregnancy seems to increase birthweight
      and the offspring's risk of obesity later in life. However, this association
      might be confounded by genetic and other shared effects. We aimed to examine the
      association between maternal weight gain and birthweight using state-based birth
      registry data that allowed us to compare several pregnancies in the same mother.
      METHODS: In this population-based cohort study, we used vital statistics natality
      records to examine all known births in Michigan and New Jersey, USA, between Jan
      1, 1989, and Dec 31, 2003. From an initial sample of women with more than one
      singleton birth in the database, we made the following exclusions: gestation less
      than 37 weeks or 41 weeks or more; maternal diabetes; birthweight less than 500 g
      or more than 7000 g; and missing data for pregnancy weight gain. We examined how
      differences in weight gain that occurred during two or more pregnancies for each
      woman predicted the birthweight of her offspring, using a within-subject design
      to reduce confounding to a minimum. FINDINGS: Our analysis included 513 501 women
      and their 1 164 750 offspring. We noted a consistent association between
      pregnancy weight gain and birthweight (beta 7.35, 95% CI 7.10-7.59, p<0.0001).
      Infants of women who gained more than 24 kg during pregnancy were 148.9 g (141.7
      156.0) heavier at birth than were infants of women who gained 8-10 kg. The odds
      ratio of giving birth to an infant weighing more than 4000 g was 2.26 (2.09-2.44)
      for women who gained more than 24 kg during pregnancy compared with women who
      gained 8-10 kg. INTERPRETATION: Maternal weight gain during pregnancy increases
      birthweight independently of genetic factors. In view of the apparent association
      between birthweight and adult weight, obesity prevention efforts targeted at
      women during pregnancy might be beneficial for offspring. FUNDING: US National
      Institutes of Health.

PMID- 20691470
TI  - Preparation of three-dimensional interconnected macroporous cellulosic hydrogels
      for soft tissue engineering.
AB  - This work exploits the thermal responsive phase behavior of
      hydroxypropylcellulose to produce 3D interconnected macroporous hydrogels in
      aqueous environment. Hydroxypropylcellulose was modified with allyl isocyanate,
      and their temperature mediated phase behavior was studied as a function of degree
      of modification (DS). A derivative with a DS of 1.5 was selected for scaffold
      preparation. Its aqueous solutions were warmed up to trigger the formation of
      biphasic systems. Such state was then immobilized efficiently by gamma-ray
      irradiated crosslinking. Lyophilization of the crosslinked hydrogels yielded 3D
      macroporous sponges. The re-hydrated gels demonstrate a combination of
      interconnected macroporosity, high water content and mechanical integrity to soft
      tissues. Cytocompatibility was demonstrated among various cell types, and in vivo
      biocompatibility test showed minimal inflammatory response within 12 weeks'
      subcutaneous implantation in mice. The potential applications of these
      macroporous hydrogels in tissue engineering are discussed.

PMID- 20691471
TI  - Tailoring the efficacy of nimodipine drug delivery using nanocarriers based on
      A2B miktoarm star polymers.
AB  - We report a nanocarrier based on A(2)B type miktoarm polymers (A=polyethylene
      glycol (PEG); B=polycaprolactone (PCL)) for nimodipine (NIM), a hydrophobic drug
      with very poor aqueous solubility that is commonly prescribed for the prevention
      and treatment of delayed ischemic neurological disorders. The A(2)B star polymers
      were constructed on a core with orthogonal functionalities that facilitated the
      performance of "click" chemistry followed by ring-opening polymerization. These
      star polymers assemble into spherical micelles into which NIM can be easily
      loaded by the co-solvent evaporation method. The micelles obtained from the star
      polymer PEG775(2)-PCL5800 showed NIM encapsulation efficiency of up to 78 wt% at
      a feed weight ratio of 5.0%. The loading efficiency of the micelles was dependent
      on the length of the PCL arm in the A(2)B miktoarm polymers. Aqueous solubility
      of NIM was increased by approximately 200 fold via micellar encapsulation. The in
      vitro release of NIM from the micelles was found to occur at a much slower rate
      than from its solution. Lipopolysaccharide induced nitric oxide production in N9
      microglia cells was reduced in the presence of micelle-encapsulated NIM, as well
      as in the presence of micelles alone. The treatment of microglia with micelle
      encapsulated NIM reduced the release of TNF-alpha, a pro-inflammatory cytokine.
      These results suggest that NIM-loaded miktoarm micelles could be useful in the
      treatment of neuroinflammation.

PMID- 20691472
TI  - Smudge cells: very old history and new conclusions.

PMID- 20691473
TI  - Biologic activity of triptolide in t(8;21) acute myeloid leukemia cells.
AB  - Triptolide is a compound isolated from the traditional Chinese medicinal herb
      Tripterygium wilfordii that shows potent anti-tumor activities, but its effects
      on acute myeloid leukemia with t(8;21) remain unclear. Here we report that
      triptolide inhibits cell proliferation and induces apoptosis in a dose- and time
      dependent manner of t(8;21)-bearing Kasumi-1, SKNO-1 and CD34+ cells harvested
      from bone marrow samples of patients with t(8;21) leukemia. We show that
      triptolide triggers cleavage of the resultant AML1-ETO fusion protein of t(8;21),
      and causes downregulation of C-KIT followed by inhibition of JAK-STAT signaling.
      Triptolide downregulates p65 and inhibits the DNA-binding activity of NF-kappaB.
      Our data indicate that triptolide might be an effective agent for t(8;21)
      leukemia.

PMID- 20691474
TI  - Myelodysplastic syndromes with deletions of chromosome 11q lack cryptic MLL
      rearrangement and exhibit characteristic clinicopathologic features.
AB  - Deletions of chromosome 11q[del(11q)] as part of a non-complex karyotype are
      infrequent in myelodysplastic syndromes (MDS), leaving the clinicopathologic and
      genetic features largely undefined. From three large medical centers over a 10
      year period, we identified 32 MDS cases where del(11q) was present either as a
      sole (n=23) or associated with another abnormality (n=9), showing an overall 0.6%
      frequency in MDS. These patients included 15 men and 17 women, with a median age
      of 68 years. Three were therapy-related, and 29 were primary MDS. These cases
      were characterized by transfusion-dependent anemia (65%); frequent ring
      sideroblasts (RS) (59%); bone marrow hypocellularity (22%), and less severe
      thrombocytopenia. With a median follow-up of 32 months, 9/24 (38%) cases
      progressed to acute myeloid leukemia (AML), and the overall survival (OS) was 35
      months (3-105). Fluorescence in situ hybridization (FISH) showed MLL deletion in
      6/10 cases, but no cryptic MLL translocations in all 15 MDS cases tested. In
      contrast, FISH performed in AML with del(11q) showed MLL rearrangement in 3/17
      (18%) cases. In summary, del(11)q occurring in a non-complex karyotype is
      predominantly associated with primary MDS, lack of cryptic MLL rearrangements,
      and shows characteristic clinicopathological features. These clinicopathological
      features are likely attributed to commonly deleted regions of 11q and their
      involved genes.

PMID- 20691475
TI  - A comparative study of different tests for biodegradability enhancement
      determination during AOP treatment of recalcitrant toxic aqueous solutions.
AB  - Four biodegradability tests (Pseudomonas putida bioassay, Zahn-Wellens test,
      BOD5/COD ratio and respirometry assay) have been used to determine the
      biodegradability enhancement during the treatment of wastewater containing 200 mg
      L(-1) of dissolved organic carbon (DOC) of a five commercial pesticides mixture
      (Vydate, Metomur, Couraze, Ditumur and Scala) by an advanced oxidation process
      (AOP). A comparative study was carried out taking into account repeatability and
      precision of each biodegradability test. Solar photo-Fenton was the AOP selected
      for pesticide degradation up to three levels of mineralization: 20%, 40% and 60%
      of initial DOC. Intra- and interday precisions were evaluated conducting each
      biodegradability test by triplicate and they were applied three times on
      different dates over a period of three months. Fisher's least significant
      difference method was applied to the means, P. putida and Zahn-Wellens tests
      giving higher repeatability and precision. The P. putida test requires a shorter
      time to obtain reliable results using a standardized inoculum and constitutes a
      worthwhile alternative to estimate biodegradability in contrast to other less
      accurate or more time consuming methods.

PMID- 20691476
TI  - Health-related quality of life in Brazilian outpatients with Chagas and non
      Chagas cardiomyopathy.
AB  - PURPOSE: To examine differences in demographic, clinical, and health-related
      characteristics of quality of life in heart failure patients with Chagas and non
      Chagas cardiomyopathy in Brazil. METHODS: This observational study was carried
      out with 43 Brazilian out-patients with Chagas and 59 non-Chagas cardiomyopathy.
      RESULTS: No differences were evident between the 2 groups regarding age, sex,
      mean left-ventricular ejection fraction, and duration of follow-up. Compared with
      the non-Chagas group, patients with Chagas cardiomyopathy had a higher percentage
      of participants using artificial pacemakers (P < .001), more symptoms of heart
      failure as measured by New York Heart Association classes III and IV (P = .02),
      higher intakes of aspirin and warfarin, a higher use of artificial pacemakers
      because of bradycardia, and lower health-related quality of life in the Physical
      Functioning (P = .01) and Role Physical (P = .002) domains of the Medical
      Outcomes Study Short Form 36-Item Health Status Survey. CONCLUSION: Our study
      population was limited to one region endemic for Chagas disease in Brazil, and
      therefore findings need to be confirmed and should not be generalized to other
      populations without further research.

PMID- 20691477
TI  - Health-related quality of life: The impact of diagnostic angiography.
AB  - BACKGROUND: Little is known regarding the effects of index angiograms on health
      related quality of life related to angiographic outcome, that is, positive or
      negative for coronary heart disease (CHD). METHODS: A longitudinal, comparative
      design was used. Ninety-three patients underwent initial angiography and
      completed questionnaires (Cardiac-Quality of Life Index, Short Form-36 mental and
      physical, and Cardiac Attitudes Index) before, 1 week and 1 year after
      angiography. Data were evaluated with linear regression and analysis of variance.
      RESULTS: Fifty-five patients were CHD positive (age 65.3 +/- 10.7 years, 49% were
      female), and 38 patients were CHD negative (age 59.5 +/- 12 years, 53% were
      female). Compared with CHD-positive patients over 1 year, CHD-negative patients
      reported lower scores on the Cardiac-Quality of Life Index (P < .008), Short Form
      36 mental and physical measures (P = .004), and Cardiac Attitudes Index (P =
      .05). CONCLUSION: CHD-negative patients experienced lower health-related quality
      of life and lower perceived control than CHD-positive patients. After an index
      angiogram, a negative finding may not be sufficient to relieve negative emotions.

PMID- 20691478
TI  - The pattern of somatic hypermutation of Ig genes is altered when p53 is
      inactivated.
AB  - Mice with a deletion of the p53 gene have normal antibody titers against sheep
      red blood cells and normal switching to all Ig isotypes. In older mice (11 and 16
      weeks old) the somatic hypermutation (SHM) frequencies are progressively reduced.
      In young mice (8 weeks old) with p53 deletion, the SHM frequencies are normal.
      However, the mutation pattern is changed in all p53-/- mice: mutations at A are
      increased. Surprisingly, deletion of the Ung2 gene in addition to the deletion of
      p53 corrected the A mutation frequencies to those of control mice. Known
      interactions of p53 protein with several proteins involved in error-prone BER
      during SHM may explain these findings. There is no indication that the absence of
      p53 affects the function of AID. Inactivation of p21 does not alter SHM,
      supporting the idea that the p53 protein is involved in SHM by its direct
      association with the SHM process. There is no significant change of mutations at
      T. Thus, the hypermutability at A is strand-biased (transcription? replication?).
      The translesion polymerase pol eta has so far been found to be the sole mutator
      at A and T in mice. However, the pattern in p53-/- mice is compatible with the
      possible inhibition by p53 of another translesion polymerase, pol iota, which in
      the absence of p53 may be recruited to error-prone repair of abasic sites in SHM.

PMID- 20691479
TI  - Rigid nylon foil-anchored polytetrafluoroetyhlene (Gore-Tex) sheet stenting for
      conjunctival fornix reconstruction.
AB  - PURPOSE: To describe an operative technique that deepens foreshortened
      conjunctival fornices by providing a scaffold for epithelialization that opposes
      contractile forces during wound healing. DESIGN: Retrospective interventional
      case series. PARTICIPANTS: Seventeen patients with anophthalmic sockets
      containing foreshortened conjunctival fornices. METHODS: Conjunctival fornices
      was reconstructed with stents of expanded polytetrafluoroethylene (e-PTFE) sheet
      draped over rigid, 0.8-mm thick-nylon strips that were anchored to the orbital
      rim. Preoperative and postoperative symptoms, prosthesis retention, fornix depth,
      and lagophthalmos were assessed. MAIN OUTCOME MEASURES: Prosthesis retention,
      fornix depth, and lagophthalmos. RESULTS: All 17 patients had preoperative
      inability to retain their prosthesis. After postoperative follow-up of 47+/-43
      months, retention was improved in all patients and was entirely satisfactory in
      15 (88%) patients. After reconstruction, the repaired fornix was deep in 7 (41%)
      patients, adequate to retain a prosthesis in 9 (53%), and shallow in 1 (6%).
      Lagophthalmos improved in 15 (88%) patients and remained unchanged in 2 (12%).
      The superior fornix was reconstructed concurrently with the inferior fornix in 6
      patients. In these patients, the superior fornix improved to deep (3 patients;
      50%) or adequate (2; 33%). In 1 (17%) patient, it remained shallow. CONCLUSIONS:
      Rigid, nylon foil-anchored e-PTFE stenting opposes postoperative contracture,
      improving prosthesis retention, and lagophthalmos. It does not require an
      additional surgical site for graft harvesting.

PMID- 20691480
TI  - Meta-analysis of 1- versus 2-Site Phacotrabeculectomy.
AB  - TOPIC: Comparison of efficacy of intraocular pressure (IOP) reduction between 1-
      versus 2-site phacotrabeculectomy. CLINICAL RELEVANCE: The last systematic review
      concluded that there was weak evidence to suggest that 2-site phacotrabeculectomy
      provides 1- to 2-mmHg lower IOP than 1-site surgery. Since this study, there have
      been further publications on this topic, stimulating this meta-analysis.
      METHODS/LITERATURE REVIEWED: Randomized controlled trials comparing 1- versus 2
      site phacotrabeculectomy were searched through August 2009 using MEDLINE and the
      Cochrane Registry with the keyword phacotrabeculectomy. Inclusion criteria were
      prospective randomized controlled trials, a minimum of 12 months of follow-up,
      and English language. Quality of the trials was assessed using Cochrane
      collaboration's tool of assessing risk of bias. The main outcome measure was IOP,
      and secondary outcomes included number of glaucoma medications, visual acuity,
      complications, and surgical time. RESULTS: Ten articles were included. There was
      no statistically significant difference in the amount of IOP reduction between 1-
      and 2-site phacotrabeculectomy. The pooled IOP decreases from baseline (95%
      confidence interval) were: 7.85 mmHg (6.76-8.92 mmHg) versus 5.83 mmHg (4.72-6.94
      mmHg) at 1 month; 8.03 mmHg (7.38-8.67 mmHg) versus 7.03 mmHg (6.35-7.71) at 3
      months; 7.78 (7.14-8.42) versus 6.75 (6.04-7.46) at 6 months; 6.44 (5.47-7.41
      mmHg) versus 6.68 mmHg (5.56-7.81 mmHg) at 12 months; 7.17 mmHg (6.45-7.89 mmHg)
      versus 6.56 mmHg (5.77-7.35 mmHg) at 24 months; and 7.76 mmHg (7.02-8.49 mmHg)
      versus 7.14 mmHg (6.36-7.92 mmHg) at 36 months for 1- versus 2-site
      phacotrabeculectomy, respectively. There was no significant difference in the
      reduction in glaucoma medications or change in visual acuity at any time point.
      CONCLUSIONS: There is no significant difference in IOP reduction between 1- and 2
      site phacotrabeculectomy.

PMID- 20691482
TI  - Relation between weight gain and clinical improvement: is there a metabolic
      threshold for second generation antipsychotics?

PMID- 20691481
TI  - Efficacy and tolerability of extended release quetiapine fumarate (quetiapine XR)
      monotherapy in major depressive disorder: a placebo-controlled, randomized study.
AB  - BACKGROUND: Evaluate the efficacy and tolerability of extended release quetiapine
      fumarate (quetiapine XR) once-daily monotherapy for patients with major
      depressive disorder (MDD). METHODS: In this 10-week, (8-week active treatment
      phase and 2-week drug-discontinuation/tapering phase), multicenter, parallel
      group, placebo-controlled, double-blind, randomized, Phase III study
      (D1448C00003: Opal), patients initially received quetiapine XR 150 mg/day or
      placebo. At Week 2, inadequate responders (<20% reduction in MADRS total score)
      were up-titrated to 300 mg/day quetiapine XR or matching placebo for the final 6
      weeks. Primary endpoint: change from randomization to Week 8 in MADRS total
      score. Secondary endpoints included: MADRS response (>=50% reduction in total
      score from randomization) and changes from randomization to Week 8 in HAM-D and
      CGI-S. RESULTS: 310 patients were randomized. At Week 8, quetiapine XR
      significantly reduced mean MADRS total score versus placebo (-16.49 vs -13.10,
      respectively; p<0.01). Mean MADRS score was significantly reduced by quetiapine
      XR versus placebo at Week 1 (p<0.05). MADRS response rates were significantly
      greater at Week 8 for quetiapine XR versus placebo (61.9% vs 48.0%, respectively;
      p<0.05). Significant changes in HAM-D total score and CGI-S were seen at Week 8
      for quetiapine XR versus placebo. Withdrawal rates due to AEs were 9.9% and 2.6%
      for quetiapine XR and placebo, respectively. Common AEs (>10% any group during
      the randomized phase) for quetiapine XR and placebo, respectively were dry mouth
      (32.9% and 6.5%), sedation (21.7% and 1.9%), somnolence (20.4% and 5.2%), and
      headache (10.5% and 10.3%). LIMITATIONS: The study was not designed to compare
      quetiapine XR 150 mg/day and 300 mg/day; it was intended to reflect dose
      titration that might occur in clinical practice. CONCLUSIONS: Quetiapine XR
      monotherapy is effective in patients with MDD, with symptom improvement seen as
      early as Week 1, and tolerability results consistent with the known profile of
      quetiapine.

PMID- 20691483
TI  - The interactions between religion, religiosity, religious delusion/hallucination,
      and treatment-seeking behavior among schizophrenic patients in Taiwan.
AB  - Religion could influence the psychopathology, treatment-seeking behavior, and
      treatment outcome in schizophrenia, but the associations between these factors
      have never been explored thoroughly, and the data in Han-Chinese society are
      scarcer still. The current study recruited 55 schizophrenic patients to explore
      the relationship between religion, psychopathology with religious content,
      treatment-seeking behavior, and outcome. Subjects with religious
      delusions/hallucinations had lower scores on functioning and higher scores on
      religiosity. The higher religiosity scores were correlated with older age, longer
      duration of illness, religious affiliation, lower preference of psychiatric
      treatment, lower functioning score, and delusion/hallucination. As to treatment
      seeking behavior, patients with religious affiliation showed less preference
      toward psychiatric treatment. Individuals with religious delusion/hallucination
      were more likely to receive magico-religious healing and not to be satisfied with
      psychiatric treatment. A more positive view of psychiatric treatment was
      predicted by lower religiosity score, higher satisfaction with psychiatric
      treatment, and lower years of education. The religiosity level seems not directly
      related to clinical severity, but it seems to be a better predictor of religious
      delusions/hallucinations than religious affiliation status. Patients with
      religious delusions/hallucinations did not necessarily have more severe
      psychopathology. There are different profiles associated with religious
      affiliation/religiosity and religious delusions/hallucinations in relation to
      treatment-seeking behavior among schizophrenia patients in Han-Chinese society.

PMID- 20691484
TI  - Rehabilitation: Periodic somatosensory stimulation increases arterial baroreflex
      sensitivity in chronic heart failure patients.
AB  - BACKGROUND: One of the beneficial effects of exercise training in chronic heart
      failure (CHF) is an improvement in baroreflex sensitivity (BRS), a prognostic
      index in CHF. In our hypothesis-generating study we propose that at least part of
      this effect is mediated by neural afferent information, and more specifically, by
      exercise-induced somatosensory nerve traffic. OBJECTIVE: To compare the effects
      of periodic electrical somatosensory stimulation on BRS in patients with CHF with
      the effects of exercise training and with usual care. METHODS: We compared in
      stable CHF patients the effect of transcutaneous electrical nerve stimulation
      (TENS, N = 23, LVEF 30 +/- 9%) with the effects of bicycle exercise training
      (EXTR, N = 20, LVEF 32 +/- 7%). To mimic exercise-associated somatosensory
      ergoreceptor stimulation, we applied periodic (2/s, marching pace) burst TENS to
      both feet. TENS and EXTR sessions were held during two successive days. RESULTS:
      BRS, measured prior to the first intervention session and one day after the
      second intervention session, increased by 28% from 3.07 +/- 2.06 to 4.24 +/- 2.61
      ms/mmHg in the TENS group, but did not change in the EXTR group (baseline: 3.37
      +/- 2.53 ms/mmHg; effect: 3.26 +/- 2.54 ms/mmHg) (P(TENS vs EXTR) = 0.02). Heart
      rate and systolic blood pressure did not change in either group. CONCLUSIONS: We
      demonstrated that periodic somatosensory input alone is sufficient and efficient
      in increasing BRS in CHF patients. This concept constitutes a basis for studies
      towards more effective exercise training regimens in the diseased/impaired, in
      whom training aimed at BRS improvement should possibly focus more on the
      somatosensory aspect.

PMID- 20691485
TI  - Cross-sectional sero-epidemiological survey of sarcoptic mange in sheep of
      Western Castile and Leon, Spain.
AB  - The aim of the present study was to determine the prevalence of Sarcoptes scabiei
      infection of ovine livestock in three provinces (Leon, Zamora and Salamanca) in
      the Western part of the Castile and Leon region in Spain, and to determine the
      association between different variables and seropositivity. A total of 3730 sheep
      sera from 373 flocks (10 sera from each flock) collected from May to September
      over the course of the years 2006 and 2007 were individually analysed by an
      indirect antibody ELISA validated for diagnosing sarcoptic mange in sheep. The
      overall flock-level true prevalence was 22.6% (95% CI: 17.8-27.4), the overall
      individual-level true prevalence within the total flocks was 7.2% (95% CI: 6.1
      8.3) and the overall individual-level true prevalence within the seropositive
      flocks was 31.3% (95% CI: 27.2-35.4). The apparent prevalences, at flock-level
      and at individual-level within the total flocks and within the seropositive
      flocks, were not statistically different (p > 0.05) when the primary production
      objective of the flock is milk vs. meat, or in smaller (< or = 276 sheep, 50th
      percentile) vs. larger flocks (> 276 sheep). The apparent prevalences, at flock
      level and at individual-level within the seropositive flocks, were, likewise, not
      statistically different between the three provinces, but the individual-level
      apparent prevalence within the total flocks showed significant variation from one
      province to another (p < or = 0.05). Sheep maintained in the Provinces of Zamora
      and Salamanca had greater odds (OR = 1.7, 95% CI: 1.2-2.6; OR = 1.9, 95% CI: 1.3
      2.8, respectively) of being seropositive than those located in Leon Province (OR
      = 1.0). The findings of the present study clearly show the need to implement in
      this region effective control measures against sarcoptic mange in sheep.

PMID- 20691486
TI  - Intraherd correlation coefficients and design effects for bovine viral diarrhoea,
      infectious bovine rhinotracheitis, leptospirosis and neosporosis in cow-calf
      system herds in North-eastern Mexico.
AB  - Knowledge of the intraherd correlation coefficient (ICC) and design (D) effect
      for infectious diseases could be of interest in sample size calculation and to
      provide the correct standard errors of prevalence estimates in cluster or two
      stage samplings surveys. Information on 813 animals from 48 non-vaccinated cow
      calf herds from North-eastern Mexico was used. The ICC for the bovine viral
      diarrhoea (BVD), infectious bovine rhinotracheitis (IBR), leptospirosis and
      neosporosis diseases were calculated using a Bayesian approach adjusting for the
      sensitivity and specificity of the diagnostic tests. The ICC and D values for
      BVD, IBR, leptospirosis and neosporosis were 0.31 and 5.91, 0.18 and 3.88, 0.22
      and 4.53, and 0.11 and 2.68, respectively. The ICC and D values were different
      from 0 and D greater than 1, therefore large sample sizes are required to obtain
      the same precision in prevalence estimates than for a random simple sampling
      design. The report of ICC and D values is of great help in planning and designing
      two-stage sampling studies.

PMID- 20691487
TI  - Glucose metabolism in mammalian cell culture: new insights for tweaking vintage
      pathways.
AB  - Cultured mammalian cells are major vehicles for producing therapeutic proteins,
      and energy metabolism in those cells profoundly affects process productivity. The
      characteristic high glucose consumption and lactate production of industrial cell
      lines as well as their adverse effects on productivity have been the target of
      both cell line and process improvement for several decades. Recent research
      advances have shed new light on regulation of glucose metabolism and its links to
      cell proliferation. This review highlights our current understanding in this area
      of crucial importance in bioprocessing and further discusses strategies for
      harnessing new findings toward process enhancement through the manipulation of
      cellular energy metabolism.

PMID- 20691488
TI  - Pharmacokinetic, pharmacodynamic and immunogenicity comparability assessment
      strategies for monoclonal antibodies.
AB  - Regulatory guidance stipulates that comparability assessment is required to
      support manufacturing process changes during the development of a biological
      product or post-approval. However, strategies for assessing the comparability of
      pre- and post-change materials are still evolving. A hierarchical risk-based
      approach is recommended, starting with analytical testing to ensure quality,
      followed by biological characterization and, if needed, in vivo pharmacokinetic
      (PK), PK-pharmacodynamic (PD), safety and/or efficacy studies. The need for an in
      vivo study and the type of study required depend on the magnitude and the
      potential impact of the changes and the timing in the development process. This
      review discusses factors affecting the PK, PD and immunogenicity of monoclonal
      antibodies, and provides guidance for determining non-clinical and clinical
      comparability assessment strategies.

PMID- 20691489
TI  - Polymer- and colloid-mediated bioassays, sensors and diagnostics.
AB  - Synthetic polymers and colloids are increasingly being exploited in bioassays to
      help measure gene expression, sequence genomes, monitor metabolic disorders and
      detect the presence of disease. This can be attributed to their potential to
      reduce reaction scales, improve throughput, lower costs and improve the
      sensitivity, selectivity, stability and reproducibility of assays. This review
      highlights the newest application areas, including some of the strategies
      employed, as well as major technical challenges and future opportunities. The
      move away from conventional assay approaches is being driven by a desire to
      improve our basic understanding of human biology, to diagnose diseases earlier,
      and to manage healthcare resources more efficiently. These endeavors are
      important owing to a rising world population and an increasing average life span.

PMID- 20691490
TI  - Linguistic and perceptual-motor contributions to the kinematic properties of the
      braille reading finger.
AB  - Recordings of the dominant finger during the reading of braille sentences by
      experienced readers reveal that the velocity of the finger changes frequently
      during the traverse of a line of text. These changes, not previously reported,
      involve a multitude of accelerations and decelerations, as well as reversals of
      direction. We investigated the origin of these velocity intermittencies (as well
      as movement reversals) by asking readers to twice read out-loud or silently
      sentences comprising high- or low-frequency words which combined to make
      grammatical sentences that were either meaningful or nonmeaningful. In a control
      condition we asked braille readers to smoothly scan lines of braille comprised of
      meaningless cell combinations. Word frequency and re-reading each contribute to
      the kinematics of finger movements, but neither sentence meaning nor the mode of
      reading do so. The velocity intermittencies were so pervasive that they are not
      easily attributable either to linguistic processing, text familiarity, mode of
      reading, or to sensory-motor interactions with the textured patterns of braille,
      but seem integral to all braille finger movements except reversals. While
      language-related processing can affect the finger movements, the effects are
      superimposed on a highly intermittent velocity profile whose origin appears to
      lie in the motor control of slow movements.

PMID- 20691491
TI  - Effect of Capsicum carotenoids on growth and ochratoxin A production by chilli
      and paprika Aspergillus spp. isolates.
AB  - The aim of this study was to determine the effect of a natural carotenoid mixture
      (Capsantal FS-30-NT), containing capsanthin and capsorubin, on growth and
      mycotoxin production of ochratoxin A-producing A. ochraceus, A. westerdijkiae,
      and A. tubingensis isolates. One isolate of each species, previously isolated
      from paprika or chilli, was inoculated on Czapek Yeast extract Agar (CYA) medium
      supplemented with different amounts of capsantal (0 to 1%) and incubated at 10,
      15 and 25 degrees C for 21days. Growth rates and lag phases were obtained, and
      OTA production was determined at 7, 14 and 21days. The taxonomically related A.
      ochraceus and A. westerdijkiae showed the same behavior at 15 degrees C, but A.
      ochraceus was able to grow at 10 degrees C and had higher growth rates at 25
      degrees C. A. tubingensis had the highest growth rates and lowest OTA production
      capacity of the assayed isolates, and it was not able to grow at 10 degrees C.
      Capsantal addition resulted in increased lag phases at 15 degrees C for all the
      strains, while growth rates remained rather constant. At 25 degrees C capsantal
      reduced growth rates, with rather constant lag phases. However, the effect of
      capsantal on OTA production was inconclusive, because it depended on temperature
      or time, and mostly was not significant. Low temperature has been a crucial
      factor in OTA production, regardless of the capsantal concentration tested,
      especially for A. tubingensis and A. westerdijkiae. Industrial storage
      temperature for paprika and chilli is approximately 10 degrees C. If this
      temperature is maintained, mould growth and OTA production should be reduced.

PMID- 20691493
TI  - Assessing the causes inducing lengthening of hospital stays by means of the
      Appropriateness Evaluation Protocol.
AB  - OBJECTIVES: The objective is to evaluate the use of the Appropriateness
      Evaluation Protocol (AEP) as a screening tool for determining the causes of the
      non-justified days to help hospitals to decrease the length of stay while
      preserving the quality of care. METHODS: Three successive cross-sectional surveys
      were conducted from 2003 till 2005, in 23 Belgian hospitals. During this period,
      10921 days were audited by means of the AEP. This study is focused on adult acute
      non-intensive care units. The appropriateness of each day of the sample was
      assessed, and for those considered as inappropriate, the reasons explaining the
      prolongation of the stay were investigated. RESULTS: The proportion of
      inappropriate days was 24.61%. There is a high variability across specialties and
      hospitals. Regarding inappropriate days, the analysis of causes of prolongation,
      globally, by bed index or by hospital, indicated clearly internal and external
      factors that lengthen stays. The most frequent reasons are waits for an
      examination (22%) and the lack of extra-hospital structures (31%). CONCLUSIONS:
      The use of AEP as a tool of internal audit to measure the proportion of non
      justified days and their causes turns out to be possible and the obtained results
      has provided some accurate and useful information for the participating, and
      allowed them to take concrete decisions which lead to shrinking of the length of
      hospital stay.

PMID- 20691492
TI  - Ferroportin disease: a systematic meta-analysis of clinical and molecular
      findings.
AB  - BACKGROUND & AIMS: Classical ferroportin disease is characterized by
      hyperferritinemia, normal transferrin saturation, and iron overload in
      macrophages. A non-classical form is characterized by additional hepatocellular
      iron deposits and a high transferrin saturation. Both forms demonstrate autosomal
      dominant transmission and are associated with ferroportin gene (SLC40A1)
      mutations. SLC40A1 encodes a cellular iron exporter expressed in macrophages,
      enterocytes, and hepatocytes. The aim of the analysis is to determine the
      penetrance of SLC40A1 mutations and to evaluate in silico tools to predict the
      functional impairment of ferroportin mutations as an alternative to in vitro
      studies. METHODS: We conducted a systematic review of the literature and meta
      analysis of the biochemical presentation, genetics, and pathology of ferroportin
      disease. RESULTS: Of the 176 individuals reported with SLC40A1 mutations, 80 were
      classified as classical phenotype with hyperferritinemia and normal transferrin
      saturation. The non-classical phenotype with hyperferritinemia and elevated
      transferrin saturation was present in 53 patients. The remaining patients had
      normal serum ferritin or the data were reported incompletely. Despite an
      increased hepatic iron concentration in all biopsied patients, significant
      fibrosis or cirrhosis was present in only 11%. Hyperferritinemia was present in
      86% of individuals with ferroportin mutations. Bio-informatic analysis of
      ferroportin mutations showed that the PolyPhen score has a sensitivity of 99% and
      a specificity of 67% for the discrimination between ferroportin mutations and
      polymorphisms. CONCLUSIONS: In contrast to HFE hemochromatosis, ferroportin
      disease has a high penetrance, is genetically heterogeneous and is rarely
      associated with fibrosis. Non-classical ferroportin disease is associated with a
      higher risk of fibrosis and a more severe overload of hepatic iron.

PMID- 20691494
TI  - CAIMAN: an online algorithm repository for Cancer Image Analysis.
AB  - CAIMAN (CAncer IMage ANalysis: http://www.caiman.org.uk) is an online algorithm
      repository that provides specifically designed algorithms to analyse the images
      produced by experiments relevant to Cancer Research and Life Sciences, especially
      vascular biology. CAIMAN is accessed through a user-friendly website where
      researchers can upload their images and the results are returned by email. CAIMAN
      does not intend to replace more sophisticated software solutions such as ImageJ,
      Matlab, or commercial packages, but it will provide a first stop where any
      researcher can upload images and can obtain quantitative results without having
      to do any programming at all.

PMID- 20691495
TI  - Pore-scale modeling of competitive adsorption in porous media.
AB  - In this paper we present a smoothed particle hydrodynamics (SPH) pore-scale
      multicomponent reactive transport model with competitive adsorption. SPH is a
      Lagrangian, particle based modeling method which uses the particles as
      interpolation points to discretize and solve flow and transport equations. The
      theory and details of the SPH pore-scale model are presented along with a novel
      method for handling surface reactions, the continuum surface reaction (CSR)
      model. The numerical accuracy of the CSR model is validated with analytical and
      finite difference solutions, and the effects of spatial and temporal resolution
      on the accuracy of the model are also discussed. The pore-scale model is used to
      study competitive adsorption for different Damkohler and Peclet numbers in a
      binary system where a plume of species B is introduced into a system which
      initially contains species A. The pore-scale model results are compared with a
      Darcy-scale model to investigate the accuracy of a Darcy-scale reactive transport
      model for a wide range of Damkohler and Peclet numbers. The comparison shows that
      the Darcy model over estimates the mass fraction of aqueous and adsorbed species
      B and underestimates the mass fractions of species A. The Darcy-scale model also
      predicts faster transport of species A and B through the system than the pore
      scale model. The overestimation of the advective velocity and the extent of
      reactions by the Darcy-scale model are due to incomplete pore-scale mixing. As
      the degree of the solute mixing decreases with increasing Peclet and Damkohler
      numbers, so does the accuracy of the Darcy-scale model.

PMID- 20691496
TI  - Use of recombinant calreticulin and cercarial transformation fluid (CTF) in the
      serodiagnosis of Schistosoma mansoni.
AB  - Schistosomiasis is traditionally diagnosed by microscopic detection of ova in
      stool samples, but this method is labour intensive and its sensitivity is limited
      by low and variable egg secretion in many patients. An alternative is an ELISA
      using Schistosoma mansoni soluble egg antigen (SEA) to detect anti-schistosome
      antibody in patient samples. SEA is a good diagnostic marker in non-endemic
      regions but is of limited value in endemic regions, mainly because of its high
      cost and limited specificity. Here we assess seven novel antigens for the
      detection of S. mansoni antibody in an endemic region (the Northern Nile Delta).
      Using recombinant S. mansoni calreticulin (CRT) and fragments thereof, anti-CRT
      antibodies were detected in the majority of 97 patients sera. The diagnostic
      value of some of these antigens was, however, limited by the presence of cross
      reacting antibody in the healthy controls, even those recruited in non-endemic
      areas. Cercarial transformation fluid (CTF), a supernatant that contains soluble
      material released by the cercariae upon transformation to the schistosomula, is
      cheaper and easier to produce than SEA. An ELISA using CTF as the detection
      antigen had a sensitivity of 89.7% and an estimated specificity of 100% when used
      in non-endemic regions, matching the performance of the established SEA ELISA.
      CTF was substantially more specific than SEA for diagnosis in the endemic region,
      and less susceptible than SEA to cross-reacting antibody in the sera of controls
      with other protozoan and metazoan infections.

PMID- 20691497
TI  - The effects of manganese and copper in vitro and in vivo on peroxidase catalytic
      cycles.
AB  - Here we present the results of in vitro and in vivo studies of the influence of
      Mn2+ and Cu2+ on the peroxidative and oxidative catalytic functions of class III
      peroxidase. Complex peroxidase catalysis by intermediates generated in the
      reaction was analyzed by utilizing the activating effect of Mn2+ and the
      inhibitory effect of Cu2+ on the oxidative reaction in vitro. p-Coumaric acid was
      used as an enzyme substrate in the peroxidative reaction and as a cofactor in the
      oxidative reaction. In order to correlate the observed in vitro effects with the
      in vivo situation, we exposed maize plants to excess concentrations of Mn2+ and
      Cu2+ in the hydroponic solutions. Copper severely arrested plant growth, while
      manganese exerted no significant effect. The effects on peroxidase activity and
      isoforms profile of root soluble and cell wall bound fractions were studied.
      Inhibition of the peroxidase oxidative function by copper was reversible,
      localized in the cell wall, and accompanied by disappearance of some and
      appearance of new cationic isoforms. Copper-mediated changes were suppressed by
      the presence of manganese, although Mn2+ treatment per se did not affect the
      activity of the peroxidase enzyme. The results on the peroxidase activity in
      maize roots grown with excess Mn2+ and Cu2+ point to the coupling between the
      oxidative cycle, root growth and different peroxidase isoforms.

PMID- 20691498
TI  - Systems involved in K+ uptake from diluted solutions in pepper plants as revealed
      by the use of specific inhibitors.
AB  - Here, the contribution of the HAK1 transporter, the AKT1 channel and a putative
      AtCHX13 homolog to K(+) uptake in the high-affinity range of concentrations in
      pepper plants was examined. The limited development of molecular tools in pepper
      plants precluded a reverse genetics study in this species. By contrast, in the
      model plant Arabidopsis thaliana, these type of studies have shown that NH(4)(+)
      and Ba(2+) may be used as specific inhibitors of the two K(+) uptake systems to
      dissect their contribution in species in which, as in pepper, specific mutant
      lines are not available. By using these inhibitors together with Na(+) and Cs(+),
      the relative contributions of CaHAK1, CaAKT1 and a putative AtCHX13 homolog to
      K(+) acquisition from diluted solutions under different regimens of K(+) supply
      were studied. The results showed that, in plants completely starved of K(+), the
      gene encoding CaHAK1 was highly expressed and this system is a major contributor
      to K(+) uptake. However, K(+) concentrations as low as 50MUM reduced CaHAK1
      expression and the CaAKT1 channel came into play, participating together with
      CaHAK1 in K(+) absorption. The contribution of a putative AtCHX13 homolog seemed
      to be low under this low K(+) supply, but it cannot be ruled out that at higher
      K(+) concentrations this system participates in K(+) uptake. Studies of this type
      allow extension of the tools developed in model plants to understand nutrition in
      important crops.

PMID- 20691499
TI  - Human T-lymphotrophic virus type 1-associated infective dermatitis: a
      comprehensive review.
AB  - Infective dermatitis (ID) is a chronic, relapsing dermatitis associated with
      human T-lymphotrophic virus (HTLV)-1 which was initially described in Jamaican
      children. Although most cases have been reported in Jamaica, ID may be seen in
      other HTLV-1 endemic areas, such as Brazil, Japan, sub-Saharan Africa, and
      Trinidad and Tobago. Since HTLV-1 infection has been implicated in the
      development of adult T-cell leukemia/lymphoma, an aggressive hematologic
      malignancy, and HTLV-1-associated myelopathy/tropical spastic paraparesis, a
      neurodegenerative disease, ID may serve as an early clinical marker for either
      condition. Although HTLV-1-associated infective dermatitis is considered by most
      to be rare, it has been increasingly diagnosed over the past 20 years; some
      suggest ID may be underdiagnosed. One should maintain suspicion of HTLV-1
      infection among individuals in or from endemic areas, recognizing the clinical
      features and prognostic implications of infectious dermatitis.

PMID- 20691500
TI  - Onychomatricoma: genome-wide analyses of a rare nail matrix tumor.
AB  - BACKGROUND: Onychomatricoma (OM) is a rare benign tumor of the nail matrix in
      which genome-wide analyses have never been performed. It is clinically
      characterized by an increased transversal curvature of the nail plate, a
      longitudinal yellowish discoloration, and splinter hemorrhages. Once the nail
      plate has been removed, fingerlike fibrokeratogenous projections appear through
      the proximal nailfold. Histologically, it is a fibroepithelial tumor with well
      established features. In this article, a comprehensive review of this tumor is
      made. OBJECTIVE: We performed a genome-wide analysis of an OM, in an attempt to
      shed light on the mechanisms underlying its development. METHODS: We report a 36
      year-old man who was given a diagnosis of OM involving his fourth right toenail.
      To investigate molecular genetic alterations, we carried out two approaches,
      fluorescent in situ hybridization and array-based comparative genomic
      hybridization, in our patient. RESULTS: Genomic testing of OM showed 34 genomic
      alterations, with most of the genomic losses being on chromosome 11. Array-based
      comparative genomic hybridization showed the deletion of 11p15.4, which harbors
      STIM-1, 11q14.2 (RP-11 292E14), which harbors the Cathepsin C gene, 11q14 (RP11
      281F10-RP11-265F24), and 11q21 (RP11-203F8 and RP11 183A22). LIMITATIONS: This
      work is an initial approach to a genome-wide study of this tumor. Further studies
      (with more cases) must be conducted to pinpoint possible candidate genes for the
      development of OM. CONCLUSIONS: Array-based comparative genomic hybridization
      showed important genomic alterations in OM, especially genomic losses. Most
      genomic losses affected the chromosome 11 in our patient. The STIM-1 and the
      Cathepsin C genes might play a role in the development of OM.

PMID- 20691501
TI  - Twenty-first century lepers: an unfortunate phrase to use?

PMID- 20691502
TI  - All that glistens may be neither gold nor clean.

PMID- 20691503
TI  - An internet-based multimedia education prototype to enhance late-stage dementia
      care: formative research results.
AB  - The goal of this project was to develop a portable, Internet-based multimedia
      education program (IBME) to provide a more efficient training resource for direct
      care workers (DCWs) who care for nursing home residents suffering from late-stage
      dementia. Thirty-four DCWs from 8 nursing homes in 8 states completed 5 posttest
      open-ended questions and 20 Likert items on the feasibility, strengths, and
      weaknesses of the IBME prototype. Pre- and post-test surveys also examined
      whether late-stage dementia care knowledge changed significantly. More than 90%
      of DCWs "agreed" or "strongly agreed" that the IBME prototype improved DCWs'
      feelings of competency and everyday care delivery. Open-ended comments offered
      several suggestions for improvement, including group-based discussion of the
      modules. Results also indicate that DCWs' late-stage dementia care knowledge
      significantly increased (P < .001) following completion of the IBME modules. The
      IBME prototype offers an online, asynchronous training strategy to enhance
      dementia-pertinent knowledge and skills related to everyday care delivery in
      nursing homes.

PMID- 20691504
TI  - Adrenal alpha2-adrenergic receptors in the aging normotensive and spontaneously
      hypertensive rat.
AB  - This study investigates alpha(2)-adrenergic receptor (alpha(2)AR) mediated
      feedback inhibition of catecholamine release from the adrenal medulla of adult
      (52 weeks) and old (98 weeks) spontaneously hypertensive rats (SHR) and
      normotensive controls Wistar Kyoto (WKY) rats. Adrenal epinephrine content as
      well as the spontaneous and the nicotinic-evoked release of epinephrine were
      similar between adult SHR and WKY rats. Aging produced a significant reduction in
      epinephrine synthesis in WKY rats. In contrast, in SHR aging produced a
      significant increase in epinephrine release without significant changes in
      epinephrine synthesis. The alpha(2)AR agonist medetomidine abolished (80-90%
      inhibition) the nicotinic-evoked release of epinephrine in adult SHR and WKY
      rats. With aging, this effect was unaltered in WKY rats but was significantly
      decreased in SHR (30% inhibition). Adrenal alpha(2A)AR mRNA levels were
      significantly reduced in old SHR compared with age matched WKY rats. In
      conclusion, in aging the alpha(2)AR mediated feedback inhibition of epinephrine
      release from the adrenal medulla is preserved in WKY rats but compromised in SHR,
      resulting in increased epinephrine release.

PMID- 20691505
TI  - NOS3 gene rs1799983 polymorphism and incident dementia in elderly stroke
      survivors.
AB  - Stroke is a major risk factor for the development of dementia in the elderly. It
      is unclear which genes influence risk of delayed dementia after stroke. We tested
      a single nucleotide polymorphism (SNP) in endothelial nitric oxide synthase
      (NOS3) gene at codon 298 (single-nucleotide polymorphism rs1799983; p.Asp298Glu)
      in a cohort of 355 older (>75 years) stroke survivors, who had detailed cognitive
      assessments from 3 months poststroke, i.e., baseline when the patients were free
      of dementia and subsequently at annual intervals. Of these, 253 participants were
      genotyped for polymorphisms in NOS3 and apolipoprotein E (APOE). Our analysis
      showed that homozygosity for NOS3 TT rather than the GT or GG genotype was a
      significant factor in the development of dementia. The presence of TT genotype
      increased risk of incident dementia compared with GG genotype; hazard ratio, 3.14
      (95% confidence interval, 1.64-5.99; p = 0.001). We hypothesize that this may be
      mediated by reduction of nitric oxide production and cerebral perfusion. Our
      findings, if replicated widely, have implications for treatments to ameliorate
      cognitive decline in stroke survivors.

PMID- 20691507
TI  - Design, synthesis and qualitative structure-activity evaluations of novel
      hexahydropyrano[3,2-c][1,2]diazepin-3(4H)-one and tetrahydropyrano[3,2-b]pyrrol
      2(1H)-one derivatives as anticancer agents.
AB  - Polysubstituted hexahydropyrano[3,2-c][1,2]diazepin-3(4H)-one and
      tetrahydropyrano[3,2-b]pyrrol-2(1H)-one derivatives were synthesized and
      biologically evaluated as novel anticancer agents. These motifs were produced by
      five steps reaction sequence in which Achmatowicz oxidative cyclization, is the
      basic protocol for such synthesis. To understand the structure-activity
      relationships of the newly synthesized motifs, two traditional medicinal
      chemistry strategies namely, ring expansion and contraction, were followed in
      this article. These studies indicated that tetrahydropyrano[3,2-b]pyrrol-2(1H)
      one derivatives are more selective for breast cancer cell line compared to other
      cell lines under investigations. Furthermore, it was found that
      hexahydropyrano[3,2-c][1,2]diazepin-3(4H)-one derivatives are potent anticancer
      agents compared to tetrahydropyrano[3,2-b]pyrrol-2(1H)-one analogs. These
      findings, however, form the foundation for further investigation in our
      continuing efforts to develop selective anticancer agents.

PMID- 20691506
TI  - Homocysteine, neural atrophy, and the effect of caloric restriction in rhesus
      monkeys.
AB  - Higher serum homocysteine (Hcy) levels in humans are associated with vascular
      pathology and greater risk for dementia, as well as lower global and regional
      volumes in frontal lobe and hippocampus. Calorie restriction (CR) in rhesus
      monkeys (Macaca mulatta) may confer neural protection against age- or Hcy-related
      vascular pathology. Hcy was collected proximal to a magnetic resonance imaging
      (MRI) acquisition in aged rhesus monkeys and regressed against volumetric and
      diffusion tensor imaging indexes using voxel-wise analyses. Higher Hcy was
      associated with lower white matter volume in pons and corpus callosum. Hcy was
      correlated with lower gray matter volume and density in prefrontal cortices and
      striatum. CR did not influence Hcy levels. However, control monkeys exhibited a
      strong negative correlation between Hcy and global gray matter, whereas no
      relationship was evident for the CR monkeys. Similar group differences were also
      seen across modalities in the splenium of the corpus callosum, prefrontal
      cortices, hippocampus, and somatosensory areas. The data suggest that CR may
      ameliorate the influence of Hcy on several important age-related parameters of
      parenchymal health.

PMID- 20691508
TI  - Isoxazole analogs of curcuminoids with highly potent multidrug-resistant
      antimycobacterial activity.
AB  - Curcumin (1), demethoxycurcumin (2) and bisdemethoxycurcumin (3), the curcuminoid
      constituents of the medicinal plant Curcuma longa L., have been structurally
      modified to 55 analogs and antimycobacterial activity against Mycobacterium
      tuberculosis has been evaluated. Among the highly active curcuminoids, the
      isoxazole analogs are the most active group, with mono-O-methylcurcumin isoxazole
      (53) being the most active compound (MIC 0.09 microg/mL). It was 1131-fold more
      active than curcumin (1), the parent compound, and was approximately 18 and 2
      fold more active than the standard drugs kanamycin and isoniazid, respectively.
      Compound 53 also exhibited high activity against the multidrug-resistant M.
      tuberculosis clinical isolates, with the MICs of 0.195-3.125 microg/mL. The
      structural requirements for a curcuminoid analog to exhibit antimycobacterial
      activity are the presence of an isoxazole ring and two unsaturated bonds on the
      heptyl chain. The presence of a suitable para-alkoxyl group on the aromatic ring
      which is attached in close proximity to the nitrogen function of the isoxazole
      ring and a free para-hydroxyl group on another aromatic ring enhances the
      biological activity.

PMID- 20691509
TI  - QSAR study of anthranilic acid sulfonamides as inhibitors of methionine
      aminopeptidase-2 using LS-SVM and GRNN based on principal components.
AB  - Quantitative relationships between molecular structure and methionine
      aminopeptidase-2 inhibitory activity of a series of cytotoxic anthranilic acid
      sulfonamide derivatives were discovered. We have demonstrated the detailed
      application of two efficient nonlinear methods for evaluation of quantitative
      structure-activity relationships of the studied compounds. Components produced by
      principal component analysis as input of developed nonlinear models were used.
      The performance of the developed models namely PC-GRNN and PC-LS-SVM were tested
      by several validation methods. The resulted PC-LS-SVM model had a high
      statistical quality (R(2)=0.91 and R(CV)(2)=0.81) for predicting the cytotoxic
      activity of the compounds. Comparison between predictability of PC-GRNN and PC-LS
      SVM indicates that later method has higher ability to predict the activity of the
      studied molecules.

PMID- 20691510
TI  - Synthesis, molecular docking and biological evaluation of Schiff base transition
      metal complexes as potential urease inhibitors.
AB  - Six transition metal compounds of Schiff base ligands were evaluated for the
      inhibitory activity on jack bean urease, of which compounds 2-6 were determined
      by single crystal X-ray analysis. It was found that copper(II) complexes 1 and 4
      showed strong inhibitory activity against jack bean urease (IC(50) = 0.52 and
      0.46 microM), compared with acetohydroxamic acid (IC(50) = 42.12 microM) as a
      positive reference. Cobalt(II), nickel(II) and zinc(II) compounds also exhibited
      potent inhibitory activity (IC(50) = 3.88-25.20 microM). A docking analysis using
      the AUTODOCK 4.0 program could explain the inhibitory activities of 1 and 4
      against urease.

PMID- 20691511
TI  - Three-dimensional quantitative structure-activity relationship CoMSIA/CoMFA and
      LeapFrog studies on novel series of bicyclo [4.1.0] heptanes derivatives as
      melanin-concentrating hormone receptor R1 antagonists.
AB  - Comparative molecular similarity indices analysis (CoMSIA) and comparative
      molecular field analysis (CoMFA) were performed on a series of bicyclo [4.1.0]
      heptanes derivatives as melanin-concentrating hormone receptor R1 antagonists
      (MCHR1 antagonists). Molecular superimposition of antagonists on the template
      structure was performed by database alignment method. The statistically
      significant model was established on sixty five molecules, which were validated
      by a test set of ten molecules. The CoMSIA model yielded the best predictive
      model with a q(2) = 0.639, non cross-validated R(2) of 0.953, F value of 92.802,
      bootstrapped R(2) of 0.971, standard error of prediction = 0.402, and standard
      error of estimate = 0.146 while the CoMFA model yielded a q(2) = 0.680, non cross
      validated R(2) of 0.922, F value of 114.351, bootstrapped R(2) of 0.925, standard
      error of prediction = 0.364, and standard error of estimate = 0.180. CoMFA
      analysis maps were employed for generating a pseudo cavity for LeapFrog
      calculation. The contour maps obtained from 3D-QSAR studies were appraised for
      activity trends for the molecules analyzed. The results show the variability of
      steric and electrostatic contributions that determine the activity of the MCHR1
      antagonist, with these results we proposed new antagonists that may be more
      potent than previously reported, these novel antagonists were designed from the
      addition of highly electronegative groups in the substituent di(i-C(3)H(7))N- of
      the bicycle [4.1.0] heptanes, using the model CoMFA which also was used for the
      molecular design using the technique LeapFrog. The data generated from the
      present study will further help to design novel, potent, and selective MCHR1
      antagonists.

PMID- 20691512
TI  - Synthesis and antioxidant activity of quinolinobenzothiazinones.
AB  - A new series of structurally diverse quinolinobenzothiazinones has been
      synthesized with the annulation of heterocyclic structural pharmacophores. The
      synthesized quinolinobenzothiazinones have been evaluated for their antioxidant
      (LPO & GSH) and radical scavenging activities (DPPH and ABTS assays).

PMID- 20691513
TI  - [A chronic ulceration of the ala nasi].

PMID- 20691514
TI  - Coffee and liver fibrosis.

PMID- 20691515
TI  - The compliance of medical staff for the routine administration of iron in the 1st
      year to their children.
AB  - BACKGROUND & AIMS: We aimed to study the personal compliance of physicians and
      nurses with recommendations for the administration of iron supplements for their
      own children and their compliance with the routine child and maternal health care
      surveillance recommended during the first year of life. METHODS: Five hundred
      physicians and nurses from Haifa and Tel Aviv area working in hospitals and the
      community were asked to answer a self administered questionnaire. The
      questionnaire included questions assessing their compliance (using a 100 mm
      analogue visual scale) with iron and vitamin A + D supplementation, immunizations
      and routine examinations at the child and maternal health care center for their
      children. RESULTS: One hundred and forty one physicians and 135 nurses (55.2%)
      cooperated and returned the questionnaire. We found that 41.2% of medical
      personnel graded their compliance with iron supplementations as 6 or less, in a
      scale of 0-10. Significant differences were found between the different
      professions. Nurses were significantly more compliant compared to physicians
      (54.9% of nurses reported full compliance compared to only 32.4% of physicians,
      (p = 0.001)). The degree of seniority also affected compliance. Specialists were
      significantly less compliant compared to interns (22% vs. 38.8% respectively).
      Certified nurses were also less compliant compared to uncertified nurses (52.9%
      vs. 61.5% respectively). Significant differences between physicians and nurses
      were also noted in A + D administration and routine health visits. Although
      nurses demonstrated more compliance with vaccinations these differences were not
      significant (p = 0.076). CONCLUSIONS: The compliance of medical staff for iron
      and A + D administration to their own children is poor especially among
      physicians.

PMID- 20691516
TI  - Reliability and validity of a new method of nurse-led assessment of trismus.
AB  - Our aim was to develop a way of measuring trismus and evaluating it in terms of
      reliability and validity for use by nurses who care for patients with head and
      neck cancer. We developed a method from existing resources and tested it for
      interoperator reliability and validity against a "gold standard". We showed that
      within the variables outlined, nursing staff could use it after minimal training
      to identify patients broadly as being "at risk", "low risk", or having "normal
      mouth opening". Interexaminer reliability was poor. There was a trend towards a
      group of people having reasonable interexaminer reliability, and this same group
      showed consistency towards the gold standard. Nurses' accuracy and consistency in
      using a simple method of assessing trismus depends on more than the method used,
      and neither validity nor reliability can be assumed. The accurate assessment of
      trismus for comparison across studies is complex, and future research must define
      exactly what method was used.

PMID- 20691517
TI  - Septic thrombosis of the cavernous sinus and dental infection.
AB  - We report a case of septic thrombosis of the cavernous sinus and dental
      infection, and highlight the clinical features to enable prompt diagnosis and
      management.

PMID- 20691518
TI  - A novel use of a classification system to audit severe maternal morbidity.
AB  - OBJECTIVE: obstetric haemorrhage remains a significant cause of maternal
      morbidity and mortality worldwide and is significant in terms of patient safety
      and quality of care. One drastic outcome of haemorrhage is the need for
      peripartum hysterectomy. A classification system that can be used to audit severe
      events such as peripartum hysterectomy would be a useful adjunct to patient
      safety systems, but it would need to account for pre-existing risk factors, such
      as previous caesarean section. One system that accounts for important risk
      factors is the Robson Ten Group Classification System (TGCS). The aim of this
      study was to examine whether the TGCS could be extended in a novel way to
      classify who required peripartum hysterectomy. SETTING: population-based matched
      case-control study data from the UK Obstetric Surveillance System was used. All
      eligible UK hospitals participated. PARTICIPANTS: women who underwent peripartum
      hysterectomy between February 2005 and February 2006 and their matched controls.
      METHODS: cases and controls were categorised using the TGCS. The odds of having a
      peripartum hysterectomy in each classification group were calculated using
      logistic regression. An adjusted analysis was undertaken controlling for
      potential confounders. FINDINGS: 307 of the 315 women who had a peripartum
      hysterectomy were classified into one of the 10 groups; 606 of the 608 control
      women were classified. Women who underwent a peripartum hysterectomy were
      predominantly from the more complex classification groups. After adjusting for
      age, ethnicity and socio-economic status, the groups with an increased odds of
      peripartum hysterectomy were those who had a previous caesarean section.
      CONCLUSIONS: the TGCS can be used in a novel way, that is, to examine an outcome
      other than caesarean section, and could be part of a new system to monitor
      patient safety. Population-based data were used as an example of how an existing
      classification system could be used in a different way from that for which it was
      created, and could make comparisons across institutions and countries while
      adjusting for case mix in a simple manner. The TGCS may not necessarily be a
      useful way to monitor other events in childbirth. Further work is needed to
      develop other classification systems which could be used as a benchmarking tools
      to monitor patient safety in maternity care.

PMID- 20691519
TI  - The safety and quality of childbirth in the context of health systems: mapping
      maternal health provision in Lebanon.
AB  - OBJECTIVE: to provide basic information on the distribution (public/private and
      geographically) and the nature of maternity health provision in Lebanon,
      including relevant health outcome data at the hospital level in order to compare
      key features of provision with maternal/neonatal health outcomes. DESIGN: a self
      completion questionnaire was sent to private hospitals by the Syndicate of
      Private Hospitals in collaboration with the study team and to all public
      hospitals in Lebanon with a functioning maternity ward by the study team in
      cooperation with the Ministry of Public Health. SETTING: childbirth in an
      institutional setting by a trained attendant is almost universal in Lebanon and
      the predominant model of care is obstetrician-led rather than midwife-led. Yet
      due to a 15-year-old civil war and a highly privatised health sector, Lebanon
      lacks systematic or publically available data on the organisation, distribution
      and quality of maternal health services. An accreditation system for private
      hospitals was recently initiated to regulate the quality of hospital care in
      Lebanon. PARTICIPANTS: in total, 58 (out of 125 eligible) hospitals responded to
      the survey (46% total response rate). Only hospital-level aggregate data were
      collected. MEASUREMENTS: the survey addressed the volume of services, mode of
      payment for deliveries, number of health providers, number of labour and
      childbirth units, availability of neonatal intensive care units, fetal monitors
      and infusion rate regulation pumps for oxytocin, as well as health outcome data
      related to childbirth care and stillbirths for the year 2008. FINDINGS: the study
      provides the first data on maternal health provision from a survey of all
      eligible hospitals in Lebanon. More than three-quarters of deliveries occur in
      private hospitals, but the Ministry of Public Health is the single most important
      source of payment for childbirth. The reported hospital caesarean section rate is
      high at 40.8%. Essential equipment for safe maternal and newborn health care is
      widely available in Lebanon, but over half of the hospitals that responded lack a
      neonatal intensive care unit. The ratio of reported numbers of midwives to
      deliveries is three times that of obstetricians to deliveries. KEY CONCLUSIONS
      AND IMPLICATIONS FOR PRACTICE: there is a need for greater interaction between
      maternal/neonatal health, health system specialists and policy makers on how the
      health system can support both the adoption of evidence-based interventions and,
      ultimately, better maternal and perinatal health outcomes.

PMID- 20691520
TI  - Metal toxicity in a sediment-dwelling polychaete: threshold body concentrations
      or overwhelming accumulation rates?
AB  - We followed the net accumulation of As, Cu and Zn in the deposit-feeding
      polychaete Arenicola marina exposed in the laboratory to natural metal
      contaminated sediments, one exposure leading to mass mortality between day 10 and
      20, and the other not causing lethality over a period of 60 days of exposure. The
      worms showed lower total accumulated metal concentrations just before mortality
      occurred (<20 days) at the lethal exposure, than after 30 days of exposure to
      sediments not causing mortality. Moreover rates of accumulation of As, Cu and Zn
      were significantly higher in the lethal exposure than in the sublethal exposure.
      Our results show that it is not possible to link mortality to a critical total
      body concentration, and we add to a growing body of literature indicating that
      metal toxicity occurs when organisms cannot cope with overwhelming influx and
      subsequent accumulation rates.

PMID- 20691521
TI  - Comparative environmental impacts of glyphosate and conventional herbicides when
      used with glyphosate-tolerant and non-tolerant crops.
AB  - The introduction of glyphosate-tolerant (GT) crops is expected to mitigate the
      environmental contamination by herbicides because glyphosate is less persistent
      and toxic than the herbicides used on non-GT crops. Here, we compared the
      environmental balances of herbicide applications for both crop types in three
      French field trials. The dynamic of herbicides and their metabolites in soil,
      groundwater and air was simulated with PRZM model and compared to field
      measurements. The associated impacts were aggregated with toxicity potentials
      calculated with the fate and exposure model USES for several environmental
      endpoints. The impacts of GT systems were lower than those of non-GT systems, but
      the accumulation in soils of one glyphosate metabolite (aminomethylphosphonic
      acid) questions the sustainability of GT systems. The magnitude of the impacts
      depends on the rates and frequency of glyphosate application being highest for GT
      maize monoculture and lowest for combination of GT oilseed rape and non-GT
      sugarbeet crops.

PMID- 20691522
TI  - Comment on the paper "Antibiotic removal from water: Elimination of amoxicillin
      and ampicillin by microscale and nanoscale iron particles." Environmental
      Pollution 157, 1626-1635.

PMID- 20691523
TI  - The effectiveness of virtual reality distraction for pain reduction: a systematic
      review.
AB  - Virtual reality technology enables people to become immersed in a computer
      simulated, three-dimensional environment. This article provides a comprehensive
      review of controlled research on the effectiveness of virtual reality (VR)
      distraction for reducing pain. To be included in the review, studies were
      required to use a between-subjects or mixed model design in which VR distraction
      was compared with a control condition or an alternative intervention in relieving
      pain. An exhaustive search identified 11 studies satisfying these criteria. VR
      distraction was shown to be effective for reducing experimental pain, as well as
      the discomfort associated with burn injury care. Studies of needle-related pain
      provided less consistent findings. Use of more sophisticated virtual reality
      technology capable of fully immersing the individual in a virtual environment was
      associated with greater relief. Overall, controlled research suggests that VR
      distraction may be a useful tool for clinicians who work with a variety of pain
      problems.

PMID- 20691525
TI  - Poverty and childhood undernutrition in developing countries: a multi-national
      cohort study.
AB  - The importance of reducing childhood undernutrition has been enshrined in the
      United Nations' Millennium Development Goals. This study explores the
      relationship between alternative indicators of poverty and childhood
      undernutrition in developing countries within the context of a multi-national
      cohort study (Young Lives). Approximately 2000 children in each of four countries
      - Ethiopia, India (Andhra Pradesh), Peru and Vietnam - had their heights measured
      and were weighed when they were aged between 6 and 17 months (survey one) and
      again between 4.5 and 5.5 years (survey two). The anthropometric outcomes of
      stunted, underweight and wasted were calculated using World Health Organization
      2006 reference standards. Maximum-likelihood probit estimation was employed to
      model the relationship within each country and survey between alternative
      measures of living standards (principally a wealth index developed using
      principal components analysis) and each anthropometric outcome. An extensive set
      of covariates was incorporated into the models to remove as much individual
      heterogeneity as possible. The fully adjusted models revealed a negative and
      statistically significant coefficient on wealth for all outcomes in all
      countries, with the exception of the outcome of wasted in India (Andhra Pradesh)
      and Vietnam (survey one) and the outcome of underweight in Vietnam (surveys one
      and two). In survey one, the partial effects of wealth on the probabilities of
      stunting, being underweight and wasting was to reduce them by between 1.4 and 5.1
      percentage points, 1.0 and 6.4 percentage points, and 0.3 and 4.5 percentage
      points, respectively, with each unit (10%) increase in wealth. The partial
      effects of wealth on the probabilities of anthropometric outcomes were larger in
      the survey two models. In both surveys, children residing in the lowest wealth
      quintile households had significantly increased probabilities of being stunted in
      all four study countries and of being underweight in Ethiopia, India (Andhra
      Pradesh) and Peru in comparison to children residing in the highest wealth
      quintile households. Random effects probit models confirmed the statistical
      significance of increased wealth in reducing the probability of being stunted and
      underweight across all four study countries. We conclude that, although multi
      faceted, childhood undernutrition in developing countries is strongly rooted in
      poverty.

PMID- 20691526
TI  - Cancer and mastery: do age and cohort matter?
AB  - The prevailing lay and medical views of cancer as an uncontrollable and
      unpredictable disease raise a question about the effect of cancer on personal
      mastery. Does cancer undermine individuals' beliefs? Are cancer survivors more
      likely than persons without cancer to feel that life is beyond their control?
      Using data from the 1994-1995 and 2004-2006 waves of the National Survey of
      Midlife Development in the United States, I compared cancer survivors and
      individuals without cancer to examine the association between cancer and personal
      mastery. According to the stress process perspective, cancer may be detrimental
      to personal mastery, whereas the positive catalyst perspective suggests that
      cancer can enhance mastery. When changes in personal mastery are placed in the
      joint context of developmental aging processes and socio-cultural transformations
      reflected in the experiences of birth cohorts, support is found for both
      perspectives. In the three oldest cohorts born between 1920s and 1940s, personal
      mastery declines with age for all participants regardless of their cancer status.
      Yet, this age-related decline is steeper among cancer survivors than their peers
      without cancer. In the two youngest cohorts born in the 1950s and 1960s,
      individuals without cancer have a higher level of personal mastery than cancer
      survivors, yet cancer survivors exhibit a more pronounced increase in mastery
      with age than persons without cancer. This study suggests that a life course
      framework can enhance our understanding of cancer-related changes in personal
      mastery because the life course perspective integrates a psychological focus on
      adult development and aging with a sociological focus on socio-historical and
      cultural contexts.

PMID- 20691527
TI  - Inequalities in child healthy development: some challenges for effective
      implementation.

PMID- 20691528
TI  - Bullying victimisation, self harm and associated factors in Irish adolescent
      boys.
AB  - School bullying victimisation is associated with poor mental health and self
      harm. However, little is known about the lifestyle factors and negative life
      events associated with victimisation, or the factors associated with self harm
      among boys who experience bullying. The objectives of the study were to examine
      the prevalence of bullying in Irish adolescent boys, the association between
      bullying and a broad range of risk factors among boys, and factors associated
      with self harm among bullied boys and their non-bullied peers. Analyses were
      based on the data of the Irish centre of the Child and Adolescent Self Harm in
      Europe (CASE) study (boys n = 1870). Information was obtained on demographic
      factors, school bullying, deliberate self harm and psychological and lifestyle
      factors including negative life events. In total 363 boys (19.4%) reported having
      been a victim of school bullying at some point in their lives. The odds ratio of
      lifetime self harm was four times higher for boys who had been bullied than those
      without this experience. The factors that remained in the multivariate logistic
      regression model for lifetime history of bullying victimisation among boys were
      serious physical abuse and self esteem. Factors associated with self harm among
      bullied boys included psychological factors, problems with schoolwork, worries
      about sexual orientation and physical abuse, while family support was protective
      against self harm. Our findings highlight the mental health problems associated
      with victimisation, underlining the importance of anti-bullying policies in
      schools. Factors associated with self harm among boys who have been bullied
      should be taken into account in the identification of boys at risk of self harm.

PMID- 20691529
TI  - Research on meaning-making and health in secular society: secular, spiritual and
      religious existential orientations.
AB  - This article proposes a framework of concepts for the field of existential
      meaning-making in secular cultures such as those of Northern Europe. Seeking an
      operational approach, we have narrowed the field's components down to a number of
      basic domains and dimensions that provide a more authentic cultural basis for
      research in secular society. Reviewing the literature, three main domains of
      existential meaning-making emerge: Secular, spiritual, and religious. In
      reconfirming these three domains, we propose to couple them with the three
      dimensions of cognition (knowing), practice (doing), and importance (being),
      resulting in a conceptual framework that can serve as a fundamental heuristic and
      methodological research tool for mapping the field of existential meaning-making
      and health. The proposed grid might contribute to clearer understanding of the
      multidimensional nature of existential meaning-making and as a guide for posing
      adequate research and clinical questions in the field.

PMID- 20691530
TI  - Oral candidal colonization in cleft patients as a function of age, gender,
      surgery, type of cleft, and oral health.
AB  - PURPOSE: To assess the colonization rate of oral Candida species and the
      influence of age, gender, oral health status, number of surgeries, and type of
      cleft. PATIENTS AND METHODS: A prospective study of 60 patients with cleft and 60
      control subjects was carried out at the Cleft Centre at King Abdullah University
      Hospital and the Maxillofacial Unit at Jordan University of Science and
      Technology between October 2007 and June 2008. Oral health was assessed using the
      Gingival, Plaque, and Decayed, Missing, and Filled (DMFT/dmft) indexes using
      World Health Organization criteria. A culture swab was obtained from the tongue
      and buccal and palatal mucosae. Candida albicans and other Candida species were
      identified using the germ tube test and the automated biochemical test panel
      VITEK. RESULTS: The colonization rate of Candida in patients with cleft (63.3%)
      was significantly higher than in healthy control subjects (18.3%). The
      colonization rate of Candida and the distribution of C albicans varied with age
      but were not significantly associated with gender in patients with cleft and
      healthy controls. The candidal colonization rate was highest in patients with
      cleft who had at least 3 surgeries (78.2%) and in patients with bilateral clefts
      (77.7%). Patients with cleft had a significantly poorer health status than
      healthy controls; however, this was not influenced by the type of the cleft or
      the number of surgeries. CONCLUSION: Patients with cleft had a significantly
      higher rate of oral candidal colonization compared with control subjects, which
      varied with age, type of cleft, and the number of surgical interventions. Oral
      health status was significantly poorer in patients with cleft.

PMID- 20691531
TI  - Adipocytokine: a new family of inflammatory and immunologic markers of
      invasiveness in major urologic surgery.
AB  - BACKGROUND: Laparoscopic surgery has been proposed to reduce surgical trauma and
      diminish patients' stress response. OBJECTIVE: To investigate the role of the
      adipocytokine, in combination with changes in other known inflammatory markers,
      in patients undergoing radical prostatectomy. DESIGN, SETTING, AND PARTICIPANTS:
      A total of 580 patients were enrolled in this prospective study. Laparoscopic
      extraperitoneal radical prostatectomy (LRP) was performed in 286 patients, and
      open retropubic radical prostatectomy (RRP) in 294 patients. INTERVENTION: Blood
      samples were collected preoperatively and up to 5 d postoperatively.
      MEASUREMENTS: Serum concentrations of acute phase markers, interleukins (IL), and
      the adipocytokine leptin were measured at each time point by means of enzyme
      linked immunosorbent assay. Clinical data were collected and analysed. RESULTS
      AND LIMITATIONS: Patients undergoing LRP had significantly lower IL-6 and
      adipocytokine levels at all measurement time points. However, biphasic kinetics
      of adipocytokine serum levels were observed during the postoperative course in
      all patients. LRP was associated with less adipocytokine and IL-6 release,
      indicating a smaller degree of surgical insult and the minimal invasive nature of
      this procedure. The limitation of this study was its nonrandomised design.
      CONCLUSIONS: Adipocytokines might serve as additional immunologic markers of
      invasiveness in major urologic surgery.

PMID- 20691532
TI  - HLA class II alleles and multiple sclerosis in Tunisian patients.
AB  - OBJECTIVE: The aim of our study was to investigate the association of HLA-DRB1
      and -DQB1 alleles with multiple sclerosis (MS) in a Tunisian population and their
      effect on age at onset and disease severity. METHODS: 58 MS patients and 105
      healthy controls were genotyped for HLA class II alleles by PCR-SSP technique.
      RESULTS: An association of MS with HLA-DRB1*15 was found (14.7% vs 3.8%, OR (95%
      CI)=4.34 (1.69-11.39), p(c)=2.5*10(-3)) after Bonferroni's correction. Moreover,
      the DRB1*15-DQB1*06 (13.8% vs 2.8%, OR (95% CI)=5.44 (1.92-17.41), p(c)=1.1*10(
      3)) and DRB1*04-DQB1*04 (8.6% vs 1.9%, OR (95% CI)=4.86 (1.36-21.62), p(c)=0.028)
      haplotypes were found to confer a susceptibility to multiple sclerosis.
      CONCLUSION: To our knowledge, this is the first study performed to analyze the
      association of HLA-DRB1/DQB1 alleles on MS susceptibility in Tunisia. The modern
      Tunisian gene pool shows some degree of heterogeneity and reflects a significant
      gene flow from Mediterranean regions.

PMID- 20691533
TI  - Decomposition of aniline in aqueous solution by UV/TiO2 process with applying
      bias potential.
AB  - Application of bias potential to the photocatalytic decomposition of aniline in
      aqueous solution was studied under various solution pH, bias potentials and
      concentrations of potassium chloride. The decomposition of aniline by UV/TiO(2)
      process was found to be enhanced with the application of bias potential of lower
      voltages; however, the electrolysis of aniline became more dominant as the
      applying bias potential exceeding 1.0 V. Based on the experimental results and
      calculated synergetic factors, the application of bias potential improved the
      decomposition of aniline more noticeably in acidic solutions than that in
      alkaline solutions. Decomposition of aniline by UV/bias/TiO(2) process in
      alkaline solutions was increased to certain extent with the concentration of
      potassium chloride present in aqueous solution. Experimental results also
      indicated that the energy consumed by applying bias potential for aniline
      decomposition by UV/bias/TiO(2) process might be much lower than that consumed
      for increasing light intensity for photocatalysis.

PMID- 20691534
TI  - Synthesis of hybrid silica materials with tunable pore structures and morphology
      and their application for heavy metal removal from drinking water.
AB  - Porous silica materials S8, S12, S16, and SBA with controllable pore structures
      and morphology were synthesized by varying the type or alkyl chain length of the
      surfactant. Diverse amino-functionalized organic-inorganic hybrid porous
      materials were then prepared by post-grafting. Depending on the relation between
      the pore diameter of the porous silica materials and the size and content of the
      moiety to be grafted, the functionalized materials exhibited varying degrees of
      decline of structure properties, i.e. regular arrangement of pores, specific
      surface area, pore size, and pore volume. The hybrid silica materials have been
      employed as heavy metal ions adsorbents from simulated drinking water at room
      temperature. The results indicated that the diverse pore structures and different
      amino group densities influence the heavy metal ions adsorption of functionalized
      silicas significantly. The best adsorbent was found to be monoamino
      functionalized silica S16-1N, which could effectively remove heavy metal Cd(II),
      Pb(II), Fe(III), as well as Mn(II). The good performance can be attributed to the
      accessibility of effective amino groups in the pores, as well as the suitable
      pore structure with high specific surface area of 728 m(2)/g and total pore
      volume of 0.34 cm(3)/g.

PMID- 20691535
TI  - Biodegradation of diesel by mixed bacteria immobilized onto a hybrid support of
      peat moss and additives: a batch experiment.
AB  - We report microbial cell immobilization onto a hybrid support of peat moss for
      diesel biodegradation. Three strains isolated from a site contaminated with
      diesel oil were used in this study: Acinetobacter sp., Gordonia sp., and
      Rhodococcus sp. To increase not only diesel adsorption but also diesel
      biodegradation, additives such as zeolite, bentonite, chitosan, and alginate were
      tested. In this study, a peat moss, bentonite, and alginate (2/2.9/0.1 g, w/w/w)
      hybrid support (PBA) was the best support matrix, considering both diesel
      physical adsorption capacity and mixed microbial immobilization.

PMID- 20691536
TI  - Predictive monitoring and diagnosis of periodic air pollution in a subway
      station.
AB  - The purpose of this study was to develop a predictive monitoring and diagnosis
      system for the air pollutants in a subway system using a lifting technique with a
      multiway principal component analysis (MPCA) which monitors the periodic patterns
      of the air pollutants and diagnoses the sources of the contamination. The basic
      purpose of this lifting technique was to capture the multivariate and periodic
      characteristics of all of the indoor air samples collected during each day. These
      characteristics could then be used to improve the handling of strong periodic
      fluctuations in the air quality environment in subway systems and will allow
      important changes in the indoor air quality to be quickly detected. The
      predictive monitoring approach was applied to a real indoor air quality dataset
      collected by telemonitoring systems (TMS) that indicated some periodic variations
      in the air pollutants and multivariate relationships between the measured
      variables. Two monitoring models--global and seasonal--were developed to study
      climate change in Korea. The proposed predictive monitoring method using the
      lifted model resulted in fewer false alarms and missed faults due to non
      stationary behavior than that were experienced with the conventional methods.
      This method could be used to identify the contributions of various pollution
      sources.

PMID- 20691537
TI  - Removal of methylene blue from aqueous solution using cotton stalk, cotton waste
      and cotton dust.
AB  - In this study, cotton stalk (CS), cotton waste (CW) and cotton dust (CD) was used
      as sorbents to remove methylene blue (MB) from aqueous solution by batch sorption
      technique. Effects of initial dye concentration, solution pH, solution
      temperature and sorbent dose on sorption were studied. It was seen that the
      removal of methylene blue increased with increasing initial dye concentration
      (from 25 to 100 mg/l), solution pH (from 5 to 10), solution temperature (from 20
      to 50 degrees C) and sorbent dose (from 0.25 to 1.50 g/50 ml). The maximum dye
      removal was reached at 90 min. Sorption isotherms were analyzed by Langmuir and
      Freundlich models at different temperatures of 20, 30, 40 and 50 degrees C, and
      the results were discussed in detail. Moreover, the thermodynamics of sorption
      were also studied. It was found that the values of standard free energy (DeltaG
      degrees ) were positive for cotton stalk and negative for cotton waste and cotton
      dust. The values of standard enthalpy (DeltaH degrees ) and entropy (DeltaS
      degrees ) were found to be positive, and the obtained results were interpreted in
      detail. The results of this study showed that cotton stalk, cotton waste and
      cotton dust could be employed as effective and low-cost materials for the removal
      of dyes from aqueous solution.

PMID- 20691538
TI  - The adsorptive removal of disinfection by-product precursors in a high-SUVA water
      using iron oxide-coated pumice and volcanic slag particles.
AB  - The main objective of this work was to study the effectiveness of iron oxide
      coated pumice and volcanic slag particles in removing disinfection by-product
      (DBP) precursors from a raw drinking water source with high specific UV
      absorbance (SUVA(254)) value. Iron oxide coating of particles significantly
      increased dissolved organic carbon (DOC) uptakes and decreased DBP formation
      after chlorination compared to uncoated particles. pH values close to neutral
      levels during adsorption and chlorination provided DOC, trihalomethane and
      haloacetic acid reductions around 60-75% employing 6 g/L coated particle dosage.
      Higher degree of DOC and DBP reductions (>85%) were obtained with increasing
      particle dose. The uptake of bromide by iron oxide surfaces was negligible and
      increasing bromide concentrations (up to 550 MUg/L) did not negatively impact the
      DOC uptake. However, due to competition between natural organic matter (NOM) and
      bicarbonate for the iron oxide surfaces, increasing bicarbonate alkalinity levels
      reduced DOC uptakes. Overall, the results indicated that the iron oxide-coated
      pumice/slag particles are effective adsorbents to remove NOM and control DBP
      formation in waters with relatively high DOC and SUVA(254) levels. However, they
      may not be effective for waters with alkalinity levels above 250 mg CaCO(3)/L.

PMID- 20691539
TI  - Association of trace elements with colloidal fractions in leachates from closed
      and active municipal solid waste landfills.
AB  - Leachates from two Czech municipal solid waste (MSW) landfills (closed site and
      active site) were size-fractionated using the cascade frontal
      filtration/ultrafiltration procedure with filter cut-offs of 3 MUm, 0.8 MUm, 0.45
      MUm, 0.1 MUm, 10 kDa and 1 kDa. To evaluate the binding of trace elements to
      colloidal particles, the filtrates were analyzed for major compounds (FAAS, ICP
      OES and HPLC) and trace elements (ICP-MS) and the obtained elemental patterns
      were statistically evaluated. Transmission electron microscopy (TEM) indicated
      that the colloids were mostly inorganic, mainly composed of carbonates and clays.
      Characteristic features of the behaviour of trace elements and the main compounds
      were more pronounced at the active landfill site. Amongst the main compounds,
      only Fe and Ca decrease significantly and have similar patterns to numerous trace
      elements, indicating their capture by colloidal particles (at least 25%).
      Arsenic, Se and Rb exhibit zero or negligible decrease in concentration in the
      leachate during the filtration procedure. This fact indicates their particularly
      high mobility, which should be considered in preventing the flux of harmful
      compounds from landfill systems.

PMID- 20691540
TI  - Calcitonin gene-related peptide as a regulator of neuronal CaMKII-CREB,
      microglial p38-NFkappaB and astroglial ERK-Stat1/3 cascades mediating the
      development of tolerance to morphine-induced analgesia.
AB  - Tolerance to morphine-induced analgesia is an intractable phenomenon, often
      hindering its prolonged applications in the clinics. The enhanced pronociceptive
      actions of spinal pain-related molecules such as calcitonin gene-related peptide
      (CGRP) may underlie this phenomenon and could be a promising target for
      intervention. We demonstrate here how CGRP regulates the development of morphine
      analgesic tolerance at the spinal level. A 7-day treatment with morphine led to
      tolerance to its analgesic effects and enhanced expression of CGRP and its
      receptor subunits calcitonin receptor-like receptor (CRLR) and receptor activity
      modifying protein 1 (RAMP1). Activation of several cell-type-specific kinase
      transcription factor cascades is required to mediate this tolerance, including
      calcium/calmodulin-dependent protein kinase II (CaMKII) and cAMP response element
      binding protein (CREB) in neurons, p38 and nuclear factor kappa B (NFkappaB) in
      microglia and extracellular signal-regulated protein kinase (ERK) and signal
      transducer and activator of transcription 1 and 3 (Stat1/3) in astrocytes,
      because inhibitors of CaMKII, p38 and ERK pathways correspondingly reduced the
      increases in phosphorylated CREB, acetylated-NFkappaB and phosphorylated Stat1/3
      levels and attenuated the development of tolerance. Interestingly, these cascades
      were linked to the regulation of glutamatergic N-methyl-d-aspartate (NMDA)
      receptor expression. Chronic morphine-induced behavioural responses and
      biochemical events were all subjugated to modulation by disrupting CGRP receptor
      signaling. Together, these data suggest that CGRP contributes to the development
      of tolerance to morphine-induced analgesia by regulating the activation of the
      neuronal CaMKII-CREB, microglial p38-NFkappaB and astroglial ERK-Stat1/3
      cascades. Targeting CGRP-associated signaling molecules may prolong or restore
      morphine's analgesic properties upon a chronic exposure.

PMID- 20691541
TI  - Dioctophyma renale (Goeze, 1782) in the abdominal cavity of a capuchin monkey
      (Cebus apella), Brazil.
AB  - This study reports a case of parasitism by Dioctophyma renale (Goeze, 1762)
      encysted in the abdominal cavity of a capuchin monkey (Cebus apella) coming from
      the Centro Nacional de Primatas, Brazil. The animal was sent to the Veterinary
      Clinic sector with an increase in abdominal volume and no occurrence of any other
      clinical signs. Upon palpation, a movable circular mass with a diameter of
      approximately 10 cm was found. Urinalysis, complete blood count and serum
      biochemistry were performed without revealing any alterations. The animal was
      then submitted to an abdominal ultrasound exam. The cyst was punctured and a
      surgical removal procedure was performed, revealing a brownish-colored
      cylindrical structure that was already deteriorated, making it impossible to
      perform morphological analysis and classification. In the sediment of the liquid
      found, eggs were encountered that had morphological characteristics compatible
      with D. renale. The objective of this paper is to report the first case of
      parasitism by D. renale in C. apella (Linnaeus, 1758).

PMID- 20691542
TI  - Quantitative and qualitative study in keratinocytes from foreskin in children:
      Perspective application in paediatric burns.
AB  - BACKGROUND: We performed a quantitative and qualitative evaluation of
      keratinocytes from foreskin in children. MATERIALS AND METHODS: We harvested 18
      foreskins after circumcision. The mean average age of the operated children was 4
      years. The keratinocytes were isolated after double-enzymatic digestion. After
      filtration and centrifugation we put the keratinocytes in culture. Then, the
      keratinocytes were cultivated on collagen lattices. The keratinocytes were
      cultured in submerged condition for 2 days and then in an air-liquid interface
      condition for further differentiation. After cultures, the cells were counted and
      a histological examination was done. An immunohistologic analysis enabled us to
      highlight the markers characteristic of neo-epidermis differentiation. RESULTS:
      After enzymatic digestion, we obtained 11.4 million cells per foreskin. After 10
      days of culture and from 2 million cells, we obtained 24 million cells. In
      contact with the collagen lattices, we obtained a neo-epidermis and we described
      the markers of keratinocytes differentiation as well as the markers of the dermo
      epidermal junction. CONCLUSION: Keratinocytes from foreskin have a high capacity
      for division. These cells can divide for long periods before differentiation.
      These observations allow us to propose foreskin keratinocytes as a potential
      source of cells to provide coverage in burns.

PMID- 20691543
TI  - Use of cigarettes to improve affect and depressive symptoms in a longitudinal
      study of adolescents.
AB  - Smoking to alleviate negative affect or improve physiological functioning (i.e.,
      self-medication) is one explanation for the association between depression and
      smoking in adolescents. This study tests whether using cigarettes to improve mood
      or physiological functioning is associated with the onset, and change over time,
      of elevated depressive symptoms. Data were drawn from the Nicotine Dependence in
      Teens study which followed 1293 participants initially aged 12-13 years in
      Montreal, Canada every three months for five years. The subsample included 662
      adolescents who had been current smokers (reported smoking during the previous
      three months) at any point during the study. Survival analysis was used to test
      whether self-medication scores predicted onset of elevated depressive symptoms.
      Changes over time in depressive symptom scores relative to self-medication scores
      were modeled in growth curve analyses controlling for sex and number of
      cigarettes smoked per week. Smokers who reported higher self-medication scores
      had higher depressive symptom scores. The interaction between self-medication
      scores and the acceleration rate in depressive symptom scores was significant and
      negative, suggesting that participants with higher self-medication scores had
      decelerated rates of change in depression over time compared to participants with
      lower self-medication scores. Smoking appears to be ineffective at reducing
      depressive symptoms. These findings are consistent with a version of the Positive
      Resource Model that suggests that smoking will not lower depressive symptoms, but
      could slow the rate of change over time. Alternatively, the perceived positive
      benefits may be the result of alleviation of symptoms of withdrawal and craving
      resulting from abstinence. The self-medication scale may identify a population at
      risk of increased levels of depressive symptoms.

PMID- 20691544
TI  - Antibiotic-induced psychosis: a link to D-alanine?

PMID- 20691545
TI  - Developmental plasticity of stem cells and diseases.
AB  - Stem cells, which reside in most tissues with high plasticity of self-renewal and
      differentiation, play a critical role in the development and maintenance
      processes of many tissues. It is reasonable to suspect that many undefined
      chronic diseases are caused by the malfunction of stem cells. In this hypothesis,
      we try to explain the origin of undefined chronic diseases by the developmental
      plasticity of stem cells. Chronic diseases are phenotypes of stem cells'
      malfunction. Mutations of multipotent stem cells at the prenatal stage can be
      used to explain phenomena of early development of diseases. In addition, stem
      cells accumulate mutations from fetus stage to aging period and usually develop
      chronic diseases in late life periods.

PMID- 20691546
TI  - Microangiopathic hemolytic anemia and leukoerythroblastic blood film heralding
      bone marrow metastatic gastroesophageal adenocarcinoma.
AB  - Despite modern technological advancements in laboratory hematology, the blood
      film remains an important diagnostic aid. Herein, we report the case of a patient
      with a history of gastric cancer, who presented seven years following apparently
      successful surgery and adjuvant chemo-radio-therapy, with blood film findings of
      microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and
      leukoerythroblastosis (LEB). Although mimicking features of thrombotic
      thrombocytopenic purpura (TTP), subsequent bone marrow examination instead
      revealed an association with occult recurrence of necrotic, metastatic gastric
      adenocarcinoma. This case report and literature review highlight these rare, but
      important, hematological manifestations of gastric cancer, and the importance of
      astute laboratory and bone marrow investigations in preventing delays in
      appropriate treatment of the underlying malignancy.

PMID- 20691547
TI  - Experts and performance in histopathology--a study in breast pathology.
AB  - This study was undertaken to determine if it was possible to identify expertise
      within Histopathologists (trainees, district general pathologists and
      pathologists with a special interest in breast disease) using an objective
      measure of performance. The method of assessment of performance is based on the
      CWS (Cochran-Weiss-Shanteau) ratio formed by the individual's ability to
      discriminate between a spectrum of disease categories and their level of
      inconsistency when assessed at intervals. The slides circulated represented the
      spectrum of breast disease seen in routine practice. The results demonstrated the
      average CWS ratio to be lowest in trainees and highest in pathologists with a
      special interest in breast pathology although there was no statistical difference
      in the CWS scores obtained between the district general pathologists and
      pathologists with a special interest. Differences in inconsistency rather than
      discriminatory ability mainly accounted for the difference in the CWS ratio
      observed between the groups studied. The study shows that the CWS ratio is
      potentially a very useful tool in the assessment of pathologists with regard to
      assessing their progress through training.

PMID- 20691548
TI  - [Cancer genetic predisposition: current events and perspectives in 2010].
AB  - Studies performed during these last 30 years have had a major impact on the
      understanding of carcinogenesis. They have opened a new field: cancer genetic
      predisposition. At the present time, most of the cancer predispositions linked to
      the alteration of one gene, associated with a high risk of cancer and with a
      specific phenotype have been identified. About 70 genes have been identified and
      have led to genetic testing. The indication of genetic testing, the management of
      at risk patients require the establishment of guidelines. The next challenge is
      the identification of cancer susceptibility genes associated with low risk or
      modifying the effect of treatment.

PMID- 20691549
TI  - Comparative susceptibility of Atlantic salmon and rainbow trout to Yersinia
      ruckeri: relationship to O antigen serotype and resistance to serum killing.
AB  - A study was undertaken to compare the virulence and serum killing resistance
      properties of Atlantic salmon and rainbow trout Yersinia ruckeri isolates. Five
      isolates, covering heat-stable O-antigen O1, O2 and O5 serotypes, were tested for
      virulence towards fry and juveniles of both species by experimental bath
      challenge. The sensitivity of 15 diverse isolates to non-immune salmon and
      rainbow trout serum was also examined. All five isolates caused significant
      mortality in salmon fry. Serotype O1 isolate 06059 caused the highest mortality
      in salmon (74% and 70% in fry and juveniles, respectively). Isolate 06041, a
      typical ERM-causing serotype O1 UK rainbow trout strain, caused mortalities in
      both rainbow trout and salmon. None of the salmon isolates caused any mortalities
      in 150-250 g rainbow trout, and only serotype O2 isolate 06060 caused any
      significant mortality (10%) in rainbow trout fry. Disease progression and
      severity was affected by water temperature. Mortality in salmon caused by the
      isolates 06059 and 05094 was much higher at 16  degrees C (74% and 33%,
      respectively) than at 12  degrees C (30 and 4% respectively). Virulent rainbow
      trout isolates were generally resistant to sera from both species, whereas salmon
      isolates varied in their serum sensitivity. Convalescent serum from salmon and
      rainbow trout that had been infected by serotype O1 isolates mediated effective
      classical pathway complement killing of serotype O1 and O5 isolates that were
      resistant to normal sera. Overall, strains recovered from infected salmon possess
      a wider range of phenotypic properties (relative virulence, O serotype and
      possession of serum-resistance factors), compared to ERM-causing rainbow trout
      isolates.

PMID- 20691550
TI  - Contribution of postmortem multidetector CT scanning to identification of the
      deceased in a mass disaster: Experience gained from the 2009 Victorian bushfires.
AB  - CT scanning of the deceased is an established technique performed on all
      individuals admitted to VIFM over the last 5 years. It is used primarily to
      assist pathologists in determining cause and manner of death but is also
      invaluable for identification of unknown deceased individuals where traditional
      methods are not possible. Based on this experience, CT scanning was incorporated
      into phase 2 of the Institute's DVI process for the 2009 Victorian bushfires. All
      deceased individuals and fragmented remains admitted to the mortuary were CT
      scanned in their body bags using established protocols. Images were reviewed by 2
      teams of 2 radiologists experienced in forensic imaging and the findings
      transcribed onto a data sheet constructed specifically for the DVI exercise. The
      contents of 255 body bags were examined in the 28 days following the fires. 164
      missing persons were included in the DVI process with 163 deceased individuals
      eventually identified. CT contributed to this identification in 161 persons. In 2
      cases, radiologists were unable to recognize commingled remains. CT was utilized
      in the initial triage of each bag's contents. If radiological evaluation
      determined that bodies were incomplete then this information was provided to
      search teams who revisited the scenes of death. CT was helpful in differentiation
      of human from non-human remains in 8 bags, recognition of human/animal
      commingling in 10 bags and human commingling in 6 bags. In 61% of cases gender
      was able to be determined on CT using a novel technique of genitalia detection
      and in all but 2 cases this was correct. Age range was able to be determined on
      CT in 94% with an accuracy of 76%. Specific identification features detected on
      CT included the presence of disease (14 disease entities in 13 cases), medical
      devices (26 devices in 19 cases) and 274 everyday metallic items associated with
      the remains of 135 individuals. CT scanning provided useful information prior to
      autopsy by flagging likely findings including the presence of non-human remains,
      at the time of autopsy by assisting in the localization of identifying features
      in heavily disfigured bodies, and after autopsy by retrospective review of images
      for clarification of issues that arose at the time of pathologist case review. In
      view of the success of CT scanning in this mass disaster, DVI administrators
      should explore the incorporation of CT services into their disaster plans.

PMID- 20691551
TI  - The importance of Guthrie cards and other medical samples for the direct matching
      of disaster victims using DNA profiling.
AB  - The identification of disaster victims through the use of DNA analysis is an
      integral part of any Disaster Victim Identification (DVI) response, regardless of
      the scale and nature of the disaster. As part of the DVI response to the 2009
      Victorian Bushfires Disaster, DNA analysis was performed to assist in the
      identification of victims through kinship (familial matching to relatives) or
      direct (self source sample) matching of DNA profiles. Although most of the DNA
      identifications achieved were to reference samples from relatives, there were a
      number of DNA identifications (12) made through direct matching. Guthrie cards,
      which have been collected in Australia over the past 30 years, were used to
      provide direct reference samples. Of the 236 ante-mortem (AM) samples received,
      21 were Guthrie cards and one was a biopsy specimen; all yielding complete DNA
      profiles when genotyped. This publication describes the use of such Biobanks and
      medical specimens as a sample source for the recovery of good quality DNA for
      comparisons to post-mortem (PM) samples.

PMID- 20691552
TI  - Epilepsy and EEG paroxysmal abnormalities in autism spectrum disorders.
AB  - The occurrence of epilepsy in autism is variable; nevertheless, EEG paroxysmal
      abnormalities (PA) are frequently recorded in patients with autism, although the
      influence of epilepsy and/or EEG PA on the autistic regression has not been
      clarified yet. We examine a large sample of 345 inpatients with autism, divided
      into three groups: (1) patients without epilepsy and EEG PA; (2) patients with
      EEG PA but no seizures; (3) patients with epilepsy including febrile convulsions.
      The prevalence of epilepsy (24.9%) and EEG PA (45.5%) was higher than that
      reported in the general population. The significant differences among the three
      groups concerned autistic regression (comparison between groups 1 and 2, p<0.05;
      comparison between groups 1 and 3, p<0.01), cerebral lesions (comparison between
      groups 1 and 2, p<0.05; between groups 1 and 3, p<0.001), and symptomatic autism
      (comparison between groups 1 and 2 as much as comparison between groups 1 and 3,
      p<0.001), which were prevalent in groups 2 and 3; while severe/profound mental
      retardation was more frequent in group 3 compared to group 1 (p<0.01). Focal
      epilepsy (43.0%) and febrile convulsions (33.7%) were frequent in the third group
      with epilepsy. EEG PA were mainly localized in temporal and central areas
      (31.4%). Only 2.6% of patients had subcontinuous/continuous EEG PA during sleep.
      Seizures and EEG PA were not related to autistic regression. EEG PA occurred
      mainly in childhood, while epilepsy tended to occur (p<0.001) as age increased.
      The age at onset of seizures had two peaks: between 0 and 5 and between 10 and 15
      years with no difference between idiopathic and symptomatic cases. In 58.5% of
      subjects aged > or = 20 years, epilepsy including febrile seizures occurred at
      some point of their lives, while cases with only EEG PA were less frequent
      (9.7%). The relationship among autism, EEG PA and epilepsy should be clarified
      and investigated. In autism, seizures and EEG PA could represent an epiphenomenon
      of a cerebral dysfunction independent of apparent lesions.

PMID- 20691553
TI  - Comparison of AngioJet rheolytic thrombectomy before direct infarct artery
      stenting with direct stenting alone in patients with acute myocardial infarction.
      The JETSTENT trial.
AB  - OBJECTIVES: The aim of this study was to determine whether rheolytic thrombectomy
      (RT) before direct infarct artery stenting as compared with direct stenting (DS)
      alone results in improved myocardial reperfusion and clinical outcome in patients
      with acute myocardial infarction. BACKGROUND: The routine removal of thrombus
      before infarct artery stenting is still a matter of debate. METHODS: This is a
      multicenter, international, randomized, 2-arm, prospective study. Eligible
      patients were patients with acute myocardial infarction, angiographic evidence of
      thrombus grade 3 to 5, and a reference vessel diameter >=2.5 mm. Coprimary end
      points were early ST-segment resolution and (99m)Tc-sestamibi infarct size. An
      alpha value = 0.05 achieved by both coprimary surrogate end points or an alpha
      value = 0.025 for a single primary surrogate end point would be considered
      evidence of statistical significance. Other surrogate end points were
      Thrombolysis In Myocardial Infarction (TIMI) flow grade 3, corrected TIMI frame
      count, and TIMI grade 3 blush. Clinical end points were a composite of major
      adverse cardiovascular events at 1, 6, and 12 months. RESULTS: From December 2005
      to September 2009, 501 patients were randomly allocated to RT before DS or to DS
      alone. The ST-segment resolution was more frequent in the RT arm as compared with
      the DS alone arm: 85.8% and 78.8%, respectively (p = 0.043), while no difference
      between groups were revealed in the other surrogate end points. The 6-month major
      adverse cardiovascular events rate was 11.2% in the thrombectomy arm and 19.4% in
      the DS alone arm (p = 0.011). The 1-year event-free survival rates were 85.2 +/-
      2.3% for the RT arm, and 75.0 +/- 3.1% for the DS alone arm (p = 0.009).
      CONCLUSIONS: Although the primary efficacy end points were not met, the results
      of this study support the use of RT before infarct artery stenting in patients
      with acute myocardial infarction and evidence of coronary thrombus. (AngioJet
      Rheolytic Thrombectomy Before Direct Infarct Artery Stenting in Patients
      Undergoing Primary PCI for Acute Myocardial Infarction [JETSTENT]; NCT00275990).

PMID- 20691554
TI  - Is it time to jettison complex mechanical thrombectomy in favor of simple manual
      aspiration devices?

PMID- 20691555
TI  - Decision making is an important aspect of health communication research.

PMID- 20691556
TI  - Student voices in Readers' Theater: exploring communication in the hidden
      curriculum.
AB  - OBJECTIVE: During the clerkship years, students often discover a misalignment
      between formal preclinical communication skills teaching and the actual practices
      of housestaff and attending role models. We developed a workshop for medical
      educators to identify how the hidden curriculum models (or fails to model)
      effective communication skills. WORKSHOP DESIGN: Using Readers' Theater,
      participants enacted and then discussed a scenario designed to trigger
      reflection. The script was adapted from an in-depth student narrative describing
      her team's use of a derogatory term to label a patient. The student must decide
      whether and how to respond. WORKSHOP OUTCOMES: Participants discussed potential
      responses to breaches of professionalism medical hierarchy, ethical conflict
      centered on conforming pressure, "holding ambivalence", and gender inequality in
      medicine. A number of communication options for the student were considered, and
      role-played. CONCLUSION: The use of student narratives in medical education helps
      learners better understand the content and nuance of the hidden curriculum.
      Readers' Theater is a powerful tool to actively invite learners to step into the
      shoes of trainees in order to glean additional perspectives. Engaging educators
      in the task of collaborative solution building using this format can help improve
      learning environments.

PMID- 20691557
TI  - Can patient-provider interaction increase the effectiveness of medical treatment
      or even substitute it?--an exploration on why and how to study the specific
      effect of the provider.
AB  - OBJECTIVE: Numerous studies demonstrate the impact of high-quality patient
      provider interaction (PPI) on health outcomes. However, transformation of these
      findings into clinical practice is still a crucial problem. One reason might be
      that health communication research rarely investigated whether PPI can increase
      the effectiveness of medical treatment and/or even substitute it. Therefore, our
      objective was to provide empirical and methodological background of why and how
      to investigate the specific effect of the provider on patients' health outcomes.
      METHODS: This is a debate paper based on a narrative (non-systematic) literature
      review in Medline and PsycINFO without any year limitation. RESULTS:
      Neurobiological evidence based on expectation and conditioning theory indicates
      that PPI is able to increase the effectiveness of medical treatment. Moreover,
      the use of creative RCT study designs described in this paper enables health
      communication researchers to investigate whether PPI is able to substitute
      medical treatment. CONCLUSION: This paper exemplifies that there exist an
      evidence-based knowledge from neurobiology as well as creative RCT designs which
      enable researcher to investigate the specific effects of PPI. PRACTICE
      IMPLICATIONS: Research on the specific effects of PPI requires intense reflection
      on which patient groups or types of illness are reasonable, suitable, and
      ethically justifiable for interventions.

PMID- 20691558
TI  - Extrahepatic portal vein aneurysm.

PMID- 20691559
TI  - Duplex ultrasound factors predicting persistent type II endoleak and increasing
      AAA sac diameter after EVAR.
AB  - OBJECTIVE: While the significance of type II endoleaks (T2ELs) on the long-term
      outcome of endovascular abdominal aneurysm repair (EVAR) to repair abdominal
      aortic aneurysms (AAAs) is debatable, duplex ultrasonography (DU) parameters have
      been suggested to be predictive of their closure or persistence. The purpose of
      this study was to determine which, if any, of these variables was associated with
      persistent T2EL or increased AAA sac diameter. METHODS: Between 1998 and 2009,
      278 patients underwent EVAR and post-operative DU surveillance during long-term
      follow-up (1-11 years) in our accredited non-invasive vascular laboratory by one
      of three experienced technologists. DU measured intra-sac flow velocity (IFV),
      spectral doppler waveform (SDW) patterns, post-EVAR sac diameter, and number of
      T2ELs. RESULTS: T2ELs developed in 14% (38/278) of patients post-EVAR. Fourteen
      patients had T2ELs that resolved, and sac diameter decreased or remained the
      same: the average IFV was 42 cm/second; SDW patterns were monophasic in five,
      biphasic in seven and bidirectional in two; and multiple T2ELs were not present
      (0%) in any patient. Twelve patients had T2ELs that persisted, but sac diameter
      decreased or remained the same: the average IFV was 47 cm/second; SDW patterns
      were monophasic in one, biphasic in five, bidirectional in five, and undetermined
      in one; and multiple T2ELs were found in 17% (2) of patients. Twelve patients had
      T2ELs that persisted and were associated with increased sac diameter: the average
      IFV was 43 cm/second, SDW patterns were monophasic in one, biphasic in two, and
      bidirectional in nine; and multiple T2ELs were identified in 75% (9) of patients.
      None of the 38 patients with T2ELs treated with selective surgical or
      endovascular intervention for enlarging sac diameters (11/12) experienced a
      ruptured aneurysm. CONCLUSION: Contrary to previous smaller reports of T2ELs and
      DU surveillance, parameters such as IFV did not correlate with increased post
      EVAR sac diameter. The presence of multiple T2ELs and bidirectional SDW may be
      the strongest factors predictive of increased sac diameter.

PMID- 20691560
TI  - Endovascular procedures for aorto-iliac occlusive disease are associated with
      superior short-term clinical and economic outcomes compared with open surgery in
      the inpatient population.
AB  - OBJECTIVES: There has been a rapid increase in the number of endovascular
      procedures performed for peripheral artery disease, and especially aorto-iliac
      occlusive disease (AIOD). Results from single-center reports suggest a benefit
      for endovascular procedures; however, these benefits may not reflect general
      practice. We used a population-based analysis to determine predictors of clinical
      and economic outcomes following open and endovascular procedures for inpatients
      with AIOD. METHODS: All patients with AIOD who underwent open and endovascular
      procedures in the Healthcare Cost and Utilization Project Nationwide Inpatient
      Sample, 2004 to 2007, were identified. Independent patient- and provider-related
      characteristics were analyzed. Clinical outcomes included complications and
      mortality; economic outcomes included length of stay (LOS) and cost (2007
      dollars). Outcomes were compared using chi2, ANOVA, and multivariate regression
      analysis. RESULTS: Four thousand, one hundred nineteen patients with AIOD were
      identified. Endovascular procedures increased by 18%. Patients who underwent
      endovascular procedures were more likely to be >=65 years of age (46% vs 37%),
      female (54% vs 49%), and in the highest quartile of household income (20% vs
      16%), all P<.05. Endovascular patients were more likely to be non-elective (41%
      vs 20%), in the highest comorbidity index group (8% vs 5%), and with iliac artery
      disease (67% vs 33%), all P<=.05. In bivariate analysis, endovascular procedures
      were associated with lower complication rates (16% vs 25%), shorter LOS (2.2 vs
      5.8 days), and lower hospital costs ($13,661 vs $17,161), all P<.001. In
      multivariate analysis, endovascular procedures had significantly lower
      complication rates and cost, and shorter LOS. CONCLUSIONS: Endovascular
      procedures have superior short-term clinical and economic outcomes compared with
      open procedures for the treatment of AIOD in the inpatient setting. Further
      studies are needed to examine long-term outcomes and access-related issues.

PMID- 20691561
TI  - Anterior shoulder instability with Bristow procedure versus conjoined tendon
      transfer alone in a simple soft-tissue model.
AB  - PURPOSE: We compared the Bristow procedure with a conjoined tendon transfer to
      investigate the role of the sling alone in restoring anterior translation in a
      simple soft-tissue instability model without bony defects. METHODS: Ten matched
      cadaveric shoulder pairs were randomly assigned to receive a Bristow procedure or
      a conjoined tendon transfer alone. Specimens were tested in a simple soft-tissue
      model with low load simulating anterior translation of the glenohumeral joint.
      The conditions (intact, cut, and repaired) and treatments (Bristow and conjoined
      tendon transfer alone) were compared for anteroposterior translation. RESULTS:
      Anterior translation increased from 3.4 +/- 0.6 mm (mean +/- SEM) to 12.0 +/- 1.3
      mm after the cut and decreased to 5.2 +/- 0.7 mm with the Bristow procedure.
      Anterior translation increased from 2.8 +/- 0.4 mm to 12.2 +/- 1.9 mm after the
      cut and decreased to 4.9 +/- 0.5 mm after conjoined tendon transfer alone.
      Although the repair increased the stability of the glenohumeral joint as
      reflected in significantly decreased anterior translation, anterior translation
      in the repaired joint was significantly greater than that in the intact condition
      for both procedures (P < .05). There were no significant differences in anterior
      translation between the 2 treatments at any test stage. CONCLUSIONS: There was no
      difference between the Bristow procedure and conjoined tendon transfer alone in
      restoring anteroposterior translation in a simple soft-tissue shoulder
      instability model with low load and no bony defect. CLINICAL RELEVANCE: Further
      investigation of the described conjoined tendon procedure should be done to
      evaluate the procedure with significant bony defects.

PMID- 20691562
TI  - Arthroscopy and the dramatic increase in frequency of anterior acromioplasty from
      1980 to 2005: an epidemiologic study.
AB  - PURPOSE: The purposes of this study was to better understand the utilization of
      anterior acromioplasty over time, in the absence of rotator cuff repair; to
      examine the relation to patient characteristics (age, sex) and types of rotator
      cuff pathology (inflammation or fibrosis, partial-thickness tearing, full
      thickness tearing undergoing debridement); and to assess the utilization of
      arthroscopy in this procedure. METHODS: Using the resources of the Rochester
      Epidemiology Project, cataloging medical records of residents in Olmsted County,
      Minnesota, we identified 246 patients who underwent anterior acromioplasty
      between 1980 and 2005. It has previously been shown that rarely does a resident
      of Olmsted County undergo an orthopaedic procedure at a facility outside the
      county. RESULTS: The incidence of anterior acromioplasty increased over time (P <
      .001), with crude rates of 3.3 per 100,000 persons in 1980 to 1985 and 19.0 per
      100,000 persons in 2000 to 2005. Sex, age, and types of rotator cuff pathology
      did not significantly change over the 26-year period. There was a dramatic shift
      from use of the open approach to the arthroscopic approach over this time period
      (P < .001) and a decrease in the concomitant performance of distal clavicle
      resection (P < .001). CONCLUSIONS: The frequency of anterior acromioplasty has
      dramatically increased over time. Increasing knowledge about this syndrome,
      including better imaging, has facilitated patient treatment for a stable spectrum
      of rotator cuff pathology (inflammation or fibrosis, partial-thickness tearing,
      full-thickness tearing undergoing debridement), as has the application of
      endoscopic surgery. LEVEL OF EVIDENCE: Level III, epidemiologic study.

PMID- 20691563
TI  - Intrathoracic fluid extravasation after hip arthroscopy.
AB  - The case of intrathoracic extravasation of irrigation fluid after hip arthroscopy
      in a 21-year-old woman is presented. In this patient intraperitoneal and
      retroperitoneal fluid collection developed, as seen in other case reports
      documenting irrigation fluid extravasation during hip arthroscopy. The patient
      presented to the emergency department on the first postoperative day complaining
      of shortness of breath. Computed tomography of the chest, abdomen, and pelvis
      showed retroperitoneal fluid, extensive abdominal ascites, and bilateral pleural
      effusions within the chest. The fluid diminished pulmonary volume by elevating
      the diaphragm and causing compression atelectasis of both lungs. The patient's
      hemodynamic status was stable and unaffected. She developed hypothermia during
      the procedure, which is consistent with other reports on extravasated irrigation
      fluid during arthroscopy. She was able to rapidly compensate for fluid overload
      and eliminated it uneventfully, with resolution of her symptoms. A similar
      procedure was performed on the contralateral hip 6 months later. During that
      procedure, there was a suspected (not confirmed) recurrence of intraperitoneal
      extravasation of the pump fluid as well as transient hypothermia, which resolved
      by the first postoperative visit. The physiologic effects of intrathoracic fluid
      accumulation and the literature regarding extravasation of irrigation fluid
      during hip arthroscopy are also reviewed.

PMID- 20691564
TI  - Three-dimensional evaluation of the cyclic loading behavior of different rotator
      cuff reconstructions.
AB  - PURPOSE: To perform a biomechanical comparison of single-row rotator cuff repairs
      with modified suture configurations versus double-row repairs using
      radiostereometric analysis (RSA). METHODS: The infraspinatus tendon and the
      humerus of 40 porcine cadaveric shoulders were marked with tantalum beads and
      placed in an RSA calibration cage that allows for calculation of 3-dimensional
      positions of the tantalum markers. The intact tendon was cyclically loaded (50
      cycles/20 N). After sharp dissection of the infraspinatus from the bone, the
      repairs were made by use of 3 single-row (modified Mason-Allen, double mattress,
      inclined mattress) and 2 double-row (modified Mason-Allen, suture bridge)
      configurations. The reconstructions were cyclically loaded for 50 cycles (10 N to
      40, 60, 80, and 100 N). Displacements under cyclic loading were quantified in the
      anteroposterior (x), craniocaudal (y), and mediolateral (z) direction. The
      craniocaudal measurements were compared with the results of a video extensometer.
      RESULTS: Cyclic loading of the intact tendon showed a mean displacement of 0.06
      +/- 0.08 mm at the x-level, 0.16 +/- 0.18 mm at the y-level, and 0.19 +/- 0.28 mm
      at the z-level. High correlations between the RSA and the video extensometer
      measurements were found (0.87). Comparison of rotator cuff repairs showed
      significant differences in gap formation at 40, 60, 80, and 100 N in the
      craniocaudal plane (P < .0001) and the mediolateral plane (P <or= .05), with the
      double-row Mason-Allen repair providing the lowest gap formation of all tested
      configurations. However, these results were not statistically significant
      compared with the single-row double-mattress repair. No significant differences
      were measured at the anteroposterior level (P > .05). CONCLUSIONS: Single-row
      repairs using modified Mason-Allen or double-mattress repair were able to achieve
      biomechanical results comparable to double-row repairs as measured by RSA and
      digital video. CLINICAL RELEVANCE: Single-row repairs, using modified suture
      configurations, were able to decrease implant costs compared with double-row
      repairs, by achieving comparable results. Furthermore, RSA gives additional
      information on the applied forces acting on the rotator cuff repair in 3
      different planes, which may help to decrease the rerupture rate of rotator cuff
      reconstructions.

PMID- 20691565
TI  - Carotid angioplasty and stenting is safe in women.
AB  - BACKGROUND: Results of randomized controlled trials have shown that carotid
      endarterectomy poses greater perioperative risks to women than to men. There are
      limited studies regarding sex differences in carotid angioplasty and stenting.
      OBJECTIVES: To compare male and female patients undergoing carotid stenting with
      regard to their intraprocedural complications and 30-day outcome. METHODS: We
      reviewed patients who underwent carotid stenting between 1997 and 2007 at our
      tertiary centre. Distal protection devices were used in all patients after 1999.
      Demographics, risk factors, intraprocedural complications, and 30-day outcomes
      were compared between female and male patients. RESULTS: Among 243 patients who
      underwent 255 procedures, 67 were women (27.6%). The mean (SD) age of the female
      patients was 72.2 +/- 8.4 years and that of the male patients was 72.0 +/- 9.6
      years (P = .83). The majority of patients had symptomatic carotid artery disease;
      11 women (16.4%) and 30 men (16.0%) were asymptomatic. The following
      intraprocedural complications were noticed in female vs male patients:
      asymptomatic carotid and/or iliac dissections 7.5% vs 0% (P = .001), minor stroke
      0% vs 1.1% (P = 1.00), major stroke 0% vs 0.5% (P = 1.00), and cardiac
      dysrhythmias 3% vs 2.7% (P = 1.00). At 30 days, the outcomes in women vs men were
      as follows: mortality 3.0% vs 3.2% (P = 1.00), major stroke 3.0% vs 2.1 % (P =
      .66), and minor stroke 3.0% vs 3.2% (P = 1.00). CONCLUSION: Although minor
      asymptomatic intraprocedural dissections were more common in women, we did not
      find any impact of sex on the 30-day outcome. We concluded that carotid stenting
      can be performed as safely in women as in men.

PMID- 20691566
TI  - Angle changes before and after cataract surgery assessed by Fourier-domain
      anterior segment optical coherence tomography.
AB  - PURPOSE: To quantify angle changes after phacoemulsification extracapsular
      cataract extraction using Fourier-domain anterior segment optical coherence
      tomography (AS-OCT). SETTING: Department of Ophthalmology, Tri-Service General
      Hospital, National Defense Medical Center, Taiwan. DESIGN: Case series. METHODS:
      Fourier-domain AS-OCT examinations were performed in patients between 15 and 91
      years of age 1 week before and 1 week after cataract surgery. The angle, angle
      opening distance at 500 MUm, and trabecular-iris space area at 500 MUm in the
      temporal and nasal quadrants were obtained. Patients were then grouped on the
      basis of age (<60 years or >=60 years) and the results compared between groups.
      RESULTS: Eighty-nine eyes of 80 patients were evaluated. The angle, angle-opening
      distance at 500 MUm, and trabecular-iris space area at 500 MUm increased
      significantly after cataract surgery in the entire study population (P<.001).
      There were larger postoperative differences in all 3 parameters in nasal and
      temporal measurements in patients 60 years or older (all P<.001). CONCLUSIONS:
      The angle changed significantly after cataract surgery, particularly in the
      temporal quadrant and its magnitudes. Postoperative angle changes were larger in
      older patients, which may be related to the increase in lens volume during the
      aging process. Fourier-domain AS-OCT can be used as a rapid and safe tool in
      addition to diagnostic gonioscopy in assessing anterior chamber angles.

PMID- 20691567
TI  - Unique affective and cognitive processes in contamination appraisals:
      Implications for contamination fear.
AB  - A large body of evidence suggests an important role of disgust in contamination
      fear (CF). A separate line of research implicates various cognitive mechanisms in
      contamination fear, including obsessive beliefs, memory biases, and delayed
      attentional disengagement from threat. This study is an initial attempt to
      integrate these two lines of research and examines whether disgust and delayed
      attention disengagement from threat explain unique or overlapping processes
      within CF. Non-clinical undergraduate students (N = 108) completed a spatial
      cueing task, which provided measures of delayed disengagement from frightening
      and disgusting cues, and a self-report measure of disgust propensity (DP).
      Participants also completed a chain of contagion task, in which they provided
      contamination appraisals of an object as a function of degrees of removal from an
      initial contaminant. Results demonstrated that DP predicted greater initial
      contamination appraisals, but a sharper decline in estimations across further
      degrees of removal from the contaminant. Delayed disengagement from disgust cues
      uniquely predicted sustained elevations in contamination estimations across
      further degrees of removal from the contaminant. These results suggest that DP
      and delayed disengagement from disgust cues explain unique and complimentary
      processes in contamination appraisals, which suggests the utility of
      incorporating the disparate affective and cognitive lines of research on CF.

PMID- 20691568
TI  - Compromised motor planning and Motor Imagery in right Hemiparetic Cerebral Palsy.
AB  - We investigated whether motor planning problems in people with Hemiparetic
      Cerebral Palsy (HCP) are paralleled by impaired ability to use Motor Imagery
      (MI). While some studies have shown that individuals with HCP can solve a mental
      rotation task, it was not clear if they used MI or Visual Imagery (VI). In the
      present study, motor planning and MI were examined in individuals with right HCP
      (n=10) and controls. Motor planning was measured using an object manipulation
      task, where participants had to anticipate the end of the motor action. MI was
      measured using a mental rotation paradigm, where participants judged laterality
      of hands presented from a back view and a palm view. To test if participants used
      MI or VI we compared reaction times of lateral versus medial rotations, under the
      assumption that MI is subject to biomechanical constraints of rotated hands, but
      VI is not. Individuals with HCP had a higher proportion of task failures due to
      inappropriate grip choice, exemplifying impaired planning. Second, individuals
      with HCP did not show a reaction time difference between lateral and medial
      rotations, indicating an impaired ability to use MI. These findings show that
      compromised motor planning in HCP is paralleled by an impairment in the ability
      to use MI. Training of MI may be a useful entry-point for rehabilitation of motor
      planning problems.

PMID- 20691569
TI  - Grammatical gender vs. natural gender in French Williams syndrome.
AB  - This article reports grammatical gender attribution scores in French Williams
      participants (N=28, mean chronological age=15.1) in an experiment similar to the
      classic one from Karmiloff-Smith (1979) where grammatical gender was pitted
      against natural gender. WS participants massively opted for the masculine gender
      as the default one, just as MA-controls did. They differed from CA-controls,
      however, in that they provided fewer sex-based responses. Splitting the WS group
      into two subgroups did not reveal a shift to sex-based responses similar to the
      one found in controls. It is argued that this latter difference could plausibly
      be related to differences in cognitive, lexical or meta-linguistic abilities.

PMID- 20691570
TI  - B-cell overexpression of Bcl-2 cooperates with p21 deficiency for the induction
      of autoimmunity and lymphomas.
AB  - Genetic abnormalities predisposing to autoimmunity generally act in a cooperative
      manner affecting one or several mechanisms regulating immunological tolerance. In
      addition, many of these genetic abnormalities are also involved in the
      development of lymphoproliferative diseases. In the present study, we have
      determined the possible cooperation between deficiencies in members of the
      Cip/Kip family of cell cycle regulators (p21(WAF1/Cip1) or p27(kip1)) and the
      overexpression of human Bcl-2 in B lymphocytes in the induction of autoimmune and
      lymphoproliferative diseases in non-autoimmune C57BL/6 (B6) mice. Unlike single
      mutant mice, B6.p21(-/-) mice transgenic for human Bcl-2 in B cells developed a
      lethal autoimmune syndrome characterized by the production of autoantibodies, the
      prominent expansion of memory B and CD4(+) T cells and the development of severe
      glomerular lesions resembling IgA nephropathy. Furthermore, these mice presented
      a high incidence of B-cell lymphoproliferative disorders. Such genetic
      cooperation in the induction of autoimmunity was not observed in B6.p27(-/-) mice
      transgenic for human Bcl-2 in B cells. Altogether, what we have demonstrated here
      is the existence of preferential interactions among particular regulators of the
      G(1)/S transition of the cell cycle and B-cell survival in the induction of
      systemic autoimmune and lymphoproliferative diseases.

PMID- 20691571
TI  - Wavelength dependency for UVA-induced suppression of recall immunity in humans.
AB  - BACKGROUND: Ultraviolet (UV) A radiation, which has both mutagenic and immune
      suppressive effects on the skin, is increasingly recognised as a key contributor
      to cutaneous carcinogenesis. Whilst short wavelength UVB (290-320 nm) is well
      recognised as an environmental health hazard, the dangers of UVA (320-400 nm) are
      relatively unexplored. OBJECTIVE: Using the nickel model of recall immunity in
      healthy human volunteers, we determined the wavelength dependency for UV-induced
      immunosuppression across the UVA spectrum. METHODS: Dose-response curves were
      established for local suppression of contact hypersensitivity responses to nickel
      at 7 wavelengths between 331 and 392 nm. RESULTS: We found a broad peak of UVA
      immune suppressive effectiveness at 364-385 nm. Whilst we had previously found
      linear dose-responses for UVB-induced immunosuppression in this model, long
      wavelength UVA caused bell-shaped, Gaussian dose-responses, suggesting different
      chromophores and mechanisms of immunosuppression for UVB and UVA. CONCLUSION: The
      immunosuppressive peak induced by longwave UVA has not been described previously
      for any species and being close to the border with visible light indicates an
      unexpected role for these long wavebands in human health and disease.

PMID- 20691572
TI  - Detection of class 1 and 2 integrons, extended-spectrum beta-lactamases and qnr
      alleles in enterobacterial isolates from the digestive tract of Intensive Care
      Unit inpatients.
AB  - In this study, we searched for extended-spectrum beta-lactamases (ESBLs), class 1
      and 2 integrons, and qnrA, qnrB and qnrS genes in 56 oxyimino-cephalosporin
      and/or ciprofloxacin-resistant enterobacterial isolates obtained from the
      gastrointestinal tract of patients admitted in an Intensive Care Unit in Uruguay.
      ESBLs were detected in 11 isolates (6 CTX-M-2, 3 CTX-M-9, 1 CTX-M-15 and 1 PER
      2). qnr genes and integrons were detected in 5 and 24 isolates, respectively.
      Eight different antibiotic resistance gene cassettes were found within six
      different genetic arrangements. Two types of complex class 1 integrons carrying
      insertion sequence ISCR1 were found, one showing bla(CTX-M-2)-orf3 and the other
      qnrA1-ampR. Ten of the thirteen isolates carrying class 2 integrons presented the
      element IS5 inserted between intI2 and dfrA1, whereas another class 2 integron
      lacked the internal stop codon usually present in intI2. This is the first report
      of the occurrence of qnrA, qnrB and bla(CTX-M-9) in Uruguay. Dissemination of the
      different groups of CTX-M enzymes (i.e. groups 1, 2 and 9) appears to be a recent
      phenomenon in South America.

PMID- 20691573
TI  - Real-time PCR for detection of the O25b-ST131 clone of Escherichia coli and its
      CTX-M-15-like extended-spectrum beta-lactamases.
AB  - CTX-M-15 has become the most prevalent extended-spectrum beta-lactamase amongst
      Escherichia coli in many countries during the past decade. Its dominance partly
      reflects the dissemination of an E. coli O25b:H4 ST131 clone that commonly
      produces this enzyme. We describe rapid real-time polymerase chain reaction (PCR)
      assays able to detect E. coli belonging to the ST131 clone and to identify
      bla(CTX-M-15)-like.

PMID- 20691574
TI  - [Surgical managing of current cutaneous infections in children].
AB  - The cutaneous infectious pathology of the child is varied and frequent. Authors
      deal with surgical infections seen in current pediatrics, which often have to
      appeal to a plastic pediatric surgeon for their treatment. Superficial infections
      of skin and pilo-sebaceous follicles are common in big children. The folliculitis
      and the boil are the most frequent. Their treatment is medical and surgical and
      does not require an antibiotic treatment in most of the cases. The primitive
      abscesses or following an anterior lesion recover from a similar treatment. Some
      localizations or risky context need a particular follow-up. The whitlow is a
      particular example and needs to have a particular follow-up because of the risk
      of hand cellulitis. Nails embodied of the child require a specialized notice
      because of their numerous clinical forms, which must be distinguished according
      to the age. Finally the necrotizing cellulitis and fasciitis are surgical
      emergencies and have a well-codified treatment. These infections in children must
      benefit from an attentive care because when they are badly treated, they can
      involve the aesthetic, functional and vital forecast.

PMID- 20691575
TI  - C-reactive protein does not impair insulin suppression of glucose release in
      primary hepatocytes.
AB  - Recent studies have suggested that CRP may interfere with insulin signaling in
      skeletal muscle and endothelial cells. The aim of this study was to determine
      whether highly purified CRP increased the rate of glucose appearance in primary
      hepatocytes in the absence or presence of insulin. Primary rat hepatocytes were
      provided glucose-free media containing 10 mM lactate, 1 mM pyruvate, 0, 1 or 10
      nM insulin, and 0 or 10 MUg/ml of purified CRP for 6h. Purified CRP did not
      increase glucose release in the absence of insulin and did not reduce the ability
      of insulin to suppress glucose release.

PMID- 20691576
TI  - Gap and tight junctions in the formation of feather branches: A descriptive
      ultrastructural study.
AB  - The present study has focused on the distribution and ultrastructure of gap and
      tight junctions responsible for the formation of the barb/barbule branching in
      developing feathers using immunocytochemical detection. Apart from desmosomes,
      both tight and gap junctions are present between differentiating barb/barbule
      cells and during keratinization. While gap junctions are rare along the perimeter
      of these cells, tight junctions tend to remain localized in nodes joining barbule
      cells and between barb cells of the ramus. Occludin and connexin-26 but not
      connexin-43 have been detected between barb medullary, barb cortical and barbule
      cells during formation of barbs. Gap junctions are present in supportive cells
      located in the vicinity of barbule cells and destined to degenerate, but no close
      junctions are present between supportive and barb/barbule cells. Close junctions
      mature into penta-laminar junctions that are present between mature barb/barbule
      cells. Immunolabeling for occludin and Cx26 is rare along these cornified
      junctions. The junctions allow barb/barbule cells to remain connected until
      feather-keratin form the mature corneous syncytium that constitutes the barbs. A
      discussion of the role of gap and tight junctions during feather morphogenesis is
      presented.

PMID- 20691578
TI  - Novel histone biotinylation marks are enriched in repeat regions and participate
      in repression of transcriptionally competent genes.
AB  - Covalent histone modifications play crucial roles in chromatin structure and
      genome stability. We previously reported biotinylation of lysine (K) residues in
      histones H2A, H3 and H4 by holocarboxylase synthetase and demonstrated that K12
      biotinylated histone H4 (H4K12bio) is enriched in repeat regions and participates
      in gene repression. The biological functions of biotinylation marks other than
      H4K12bio are poorly understood. Here, novel biotinylation site-specific
      antibodies against H3K9bio, H3K18bio and H4K8bio were used in chromatin
      immunoprecipitation studies to obtain first insights into possible biological
      functions of these marks. Chromatin immunoprecipitation assays were conducted in
      human primary fibroblasts and Jurkat lymphoblastoma cells, and revealed that
      H3K9bio, H3K18bio and H4K8bio are enriched in repeat regions such as
      pericentromeric alpha satellite repeats and long-terminal repeats while being
      depleted in transcriptionally active promoters in euchromatin. Transcriptional
      stimulation of the repressed interleukin-2 promoter triggered a rapid depletion
      of histone biotinylation marks at this locus in Jurkat cells, which was
      paralleled by an increase in interleukin-2 mRNA. Importantly, the enrichment of
      H3K9bio, H3K18bio and H4K8bio at genomic loci depended on the concentration of
      biotin in culture media at nutritionally relevant levels, suggesting a novel
      mechanism of gene regulation by biotin.

PMID- 20691579
TI  - A novel sweet taste cell-based sensor.
AB  - In this paper, a novel sweet taste cell-based sensor is proposed for tastants
      detection. The human colorectal carcinoma NCI-H716 cell lines, which express
      alpha-gustducin and sweet taste receptor T1R1/T1R3, are cultured on the carbon
      screen-printed electrode with the pre-coated poly-L-ornithine and lamimin for
      adhesion in extracellular matrix. The electrode is placed into a fluidic and
      environment regulation system. When stimulated by an electric field at a fixed
      frequency of 1 kHz and 10 MUA, the electrochemical impedance spectrum data was
      recorded by EG&G 273A and high performance dual phase analog lock-in amplifier
      5210 and processed by bistable stochastic resonance method. Four basic tastants
      and sucrose solutions in seven concentrations can be decided by maximums of the
      signal-to-noise ratio and relevant noise intensity. A negative control experiment
      utilizing COLO-205 cell lines demonstrate that carbon screen-printed electrode
      with mammalian cell line without the expression of gust TIR2 and TIR3 lacked the
      tastant detecting ability. The sensor system presents good stability and
      repeatability. The proposed sensor is promising for practical applications, and
      provides a novel way for taste mechanism investigation.

PMID- 20691580
TI  - Synthetic gene networks in mammalian cells.
AB  - The design and construction of synthetic gene circuits with complex
      spatiotemporal dynamics was pioneered in bacteria, but it took almost a decade
      until synthetic biologists were able to construct genetic circuits with complex
      spatiotemporal dynamics in mammalian cells. This review highlights the most
      recent advances in mammalian synthetic biology, and it describes metabolite,
      hormone, and light-triggered genetic switches as well as the design and
      construction of synthetic networks that feature tunable oscillations. We conclude
      by discussing not only the current limitations but also possible ways to
      transform the construction of synthetic mammalian systems from an art into a
      predictive engineering discipline.

PMID- 20691581
TI  - Microbial rhodopsins in the spotlight.
AB  - The discovery of the light-gated cation channel Channelrhodopsin-2 (ChR2) and the
      use of the rediscovered light-driven Cl-pump halorhodopsin (HR) as optogenetic
      tools--genetically encoded switches that enable neurons to be turned on or off
      with bursts of light--refines the functional study of neurons in larger networks.
      Cell-specific expression allows a fast optical scanning approach to determine
      neuronal crosstalk following plasticity at the single synapse level or long-range
      projections in locomotion and somatosensory networks. Both rhodopsins proved to
      work functionally and could evoke behavioral responses in lower model organisms,
      reinstall rudimentary visual perception in blind mice and were set in a
      biomedical context with the investigation of neurodegenerative diseases.

PMID- 20691582
TI  - Plasticity of voltage-gated ion channels in pyramidal cell dendrites.
AB  - Dendrites of pyramidal neurons integrate multiple synaptic inputs and transform
      them into axonal action potential output. This fundamental process is controlled
      by a variety of dendritic channels. The properties of dendritic ion channels are
      not static but can be modified by neuronal activity. Activity-dependent changes
      in the density, localization, or biophysical properties of dendritic voltage
      gated channels can persistently alter the integration of synaptic inputs.
      Furthermore, dendritic intrinsic plasticity can induce neuronal output mode
      transitions (e.g. from regular spiking to burst firing). Recent advances in the
      field reviewed here represent an important step toward uncovering the principles
      of neuronal input/output transformations in response to various patterns of brain
      activity.

PMID- 20691583
TI  - Association between Epstein-Barr virus infection and risk for development of
      pregnancy-associated breast cancer: joint effect with vitamin D?
AB  - BACKGROUND: Few studies have evaluated the role of the ubiquitous Epstein-Barr
      virus (EBV) infection, together with levels of the immunomodulator, vitamin D, in
      different breast cancer entities. We studied, prospectively, the association of
      EBV and vitamin D status with the risk of pregnancy-associated breast cancer
      (PABC), breast cancer diagnosed during pregnancy or 1 year post-partum, using a
      nested case-control study. METHODS: Serum vitamin D and antibodies to EBV were
      measured for 108 PABC cases of the Finnish Maternity Cohort, and 208 controls
      matched for date of birth, date of sampling and parity. The joint effect of
      vitamin D and EBV on the risk of PABC was evaluated. RESULTS: EBV seropositivity
      was generally not associated with the risk of PABC. Among individuals with
      sufficient (>=75 nmol/l) levels of vitamin D, we, however, found similar
      increased risk estimates for PABC associated with serum immunoglobulin G (IgG)
      antibodies to EBV early antigens [odds ratio (OR)=7.7, 95% (confidence interval)
      CI 1.4-42.3] and the viral reactivator protein, ZEBRA (OR=7.8, 95% CI 1.1-61.2).
      CONCLUSION: Immunological markers of EBV reactivation status among individuals
      with sufficient vitamin D levels were consistently associated with increased risk
      of the disease. This suggests that EBV reactivation may be an indicator of the
      progression of breast cancer occurring soon after pregnancy, while the virus
      probably is not the aetiological agent.

PMID- 20691584
TI  - Dose-escalation models for combination phase I trials in oncology.
AB  - Designing combination drug phase I trials has become increasingly complex, due to
      the increasing diversity in classes of agents, mechanisms of action, safety
      profiles and drug-administration schedules. With approximately 850 agents
      currently in development for cancer treatment, it is evident that combination
      development must be prioritised, as based on a specific hypothesis, as well as a
      projected development path for the involved combination. In this manuscript the
      most relevant issues and pitfalls for combination drug phase I trial design are
      discussed. Several phase I study designs that incorporate controls to circumvent
      bias due to imbalances in observed background toxicity are discussed.

PMID- 20691585
TI  - Naturally occurring 2-substituted (1,3)-beta-D-glucan producing Lactobacillus
      suebicus and Pediococcus parvulus strains with potential utility in the
      production of functional foods.
AB  - We have isolated three lactic acid bacteria (Lactobacillus suebicus CUPV221,
      Pediococcus parvulus CUPV1 and P. parvulus CUPV22) that produced high levels of 2
      substituted (1,3)-beta-D-glucans which increased the viscosity of the growth
      media. The (1,3)-beta-D-glucan consisted of two main molecular species, with
      masses of approximately 10(7) and 10(4) Da, whose proportions varied among the
      strains. The three strains survived exposure to saliva and simulated gastric
      conditions at pH 5, with P. parvulus CUPV22 surviving at pH 3.1, and L. suebicus
      CUPV221 surviving at pH 1.8. All strains were resistant to pancreatin and bile
      salts. P. parvulus CUPV22 exhibited the highest adhesion (10.5%) to Caco-2 cells,
      which decreased to 1.2% after washing the cells. Finally, P. parvulus CUPV22 and
      L. suebicus CUPV221 induced the production of inflammation-related cytokines by
      polarized macrophages, and interestingly, L. suebicus stimulated the production
      of cytokine IL-10. These results indicate that the three strains have potential
      utility for the production of functional foods.

PMID- 20691586
TI  - Improving the thermostability of Geobacillus stearothermophilus xylanase XT6 by
      directed evolution and site-directed mutagenesis.
AB  - Protein engineering of the thermostable xylanase XT6 from Geobacillus
      stearothermophilus was performed to obtain enzymes with improved thermal
      tolerance. Mutants producing such enzymes were obtained after several rounds of
      directed evolution using error-prone PCR and sequence family shuffling, in
      combination with a consensus-based semi-rational approach. The most thermostable
      mutant enzyme contained 13 amino acid substitutions and its half-life of
      inactivation was 52-fold of that of the wild-type. Its reaction temperature for
      maximum activity increased from 77 degrees C to 87 degrees C, and catalytic
      efficiency (k(cat)/K(m)) increased by 90%. The mutant is of potential interest
      for industrial applications.

PMID- 20691587
TI  - Biodegradation of anthracene and benz[a]anthracene by two Fusarium solani strains
      isolated from mangrove sediments.
AB  - An investigation was undertaken on the biodegradation of two kinds of polycyclic
      aromatic hydrocarbons (PAHs), anthracene (ANT) and benz[a]anthracene (BAA), by
      fungi isolated from PAH-contaminated mangrove sediments environment in Ma Wan,
      Hong Kong. ANT (50mg l(-1)) and BAA (20mg l(-1)), respectively, were added to
      mineral salt medium initially for screening of PAH-degrading fungi, and finally
      two fungal species capable of using ANT or BAA as the sole carbon source were
      isolated and identified as Fusariumsolani species. Removal of ANT and BAA reached
      40% and 60% of the added amount, respectively, after 40 days of incubation. A
      total of six metabolites were isolated and characterized by solid phase
      microextraction (SPME) combined with gas chromatography-mass spectrometry
      (GC/MS), which indicate that F.solani degraded both ANT and BAA via their
      respective quinone molecules to generate phthalic acid. Free extracellular
      laccase was detected during the degradation process without detectable lignin
      peroxidase (LiP) and manganese-dependent peroxidase (MnP), suggesting that
      laccase might play an important role in the transformation of PAHs compounds.

PMID- 20691588
TI  - Bioflocculation of grey water for improved energy recovery within decentralized
      sanitation concepts.
AB  - Bioflocculation of grey water was tested with a lab-scale membrane bioreactor in
      order to concentrate the COD. Three concentration factors were tested based on
      the ratio of sludge retention time (SRT) and hydraulic retention time (HRT): 3, 8
      and 12. COD concentration factor was up to 7.1, achieving a final concentration
      of 7.2 g COD L(-1). Large fractions of suspended COD were recovered in the
      concentrate (57%, 81% and 82% at SRT/HRT ratios of 3, 8 and 12, respectively)
      indicating a strong bioflocculation of grey water. A maximum of 11% of COD
      mineralization of grey water was measured at the longest SRT tested (1 d). The
      integration of bioflocculation of grey water in decentralized sanitation concepts
      may increase the overall production of methane by 73%, based on the biogas
      produced by black water only. Therefore, bioflocculation is a promising grey
      water pre-treatment step for energy recovery within decentralized sanitation
      concepts.

PMID- 20691589
TI  - Design, synthesis, and biological evaluation of new monoamine reuptake inhibitors
      with potential therapeutic utility in depression and pain.
AB  - Two new series of monoamine triple reuptake inhibitors (TRIs) have been
      discovered through scaffold homologation of our recently reported series of 3,3
      disubstituted pyrrolidine TRIs. The regioisomeric 2- and 3-ketopyrrolidines
      demonstrated high levels of potency against all three monoamine transporters as
      well as good human in vitro stability, low drug-drug interaction potential and a
      decreased propensity for hERG channel binding. Representative compounds from
      these series displayed good in vivo pharmacokinetics and high monoamine receptor
      occupancies which are indicators of good brain penetration.

PMID- 20691590
TI  - Disorders of muscle lipid metabolism: diagnostic and therapeutic challenges.
AB  - Disorders of muscle lipid metabolism may involve intramyocellular triglyceride
      degradation, carnitine uptake, long-chain fatty acids mitochondrial transport, or
      fatty acid beta-oxidation. Three main diseases leading to permanent muscle
      weakness are associated with severe increased muscle lipid content (lipid storage
      myopathies): primary carnitine deficiency, neutral lipid storage disease and
      multiple acyl-CoA dehydrogenase deficiency. A moderate lipidosis may be observed
      in fatty acid oxidation disorders revealed by rhabdomyolysis episodes such as
      carnitine palmitoyl transferase II, very-long-chain acyl-CoA dehydrogenase,
      mitochondrial trifunctional protein deficiencies, and in recently described
      phosphatidic acid phosphatase deficiency. Respiratory chain disorders and
      congenital myasthenic syndromes may also be misdiagnosed as fatty acid oxidation
      disorders due to the presence of secondary muscle lipidosis. The main biochemical
      tests giving clues for the diagnosis of these various disorders are measurements
      of blood carnitine and acylcarnitines, urinary organic acid profile, and search
      for intracytoplasmic lipid on peripheral blood smear (Jordan's anomaly). Genetic
      analysis orientated by the results of biochemical investigation allows
      establishing a firm diagnosis. Primary carnitine deficiency and multiple acyl-CoA
      dehydrogenase deficiency may be treated after supplementation with carnitine,
      riboflavine and coenzyme Q10. New therapeutic approaches for fatty acid oxidation
      disorders are currently developed, based on pharmacological treatment with
      bezafibrate, and specific diets enriched in medium-chain triglycerides or
      triheptanoin.

PMID- 20691591
TI  - Predictors of malignancy in screen-detected breast masses with
      indeterminate/equivocal (grade 3) imaging features.
AB  - BACKGROUND: The mammographic grading system used by BreastScreen Australia
      accredited programs requires needle biopsy of lesions with indeterminate features
      (grade 3). We wished to determine the predictors of malignancy for these common
      lesions, so as to reduce surgery for benign lesions. DESIGN: Grade 3 masses
      assessed between Jan 1996-Dec 2005 are included. New or changing lesions were
      identified through film review. Imaging, demographic and final outcome data were
      tabulated. Statistical analysis was performed to determine the predictors of
      malignancy. RESULTS: 1181 lesions, including 623 new or changing masses are
      assessed. Of these 98 (8.3%) were malignant. Malignancy was found in 3% first
      round masses versus 13% of new or changing lesions. Withholding needle biopsy
      results, interval change (OR 2.85, p = 0.0001), increasing age (p = 0.0001) and
      diameter were independent predictors of malignancy, lesion diameter having an
      inverse relationship with malignancy. Once needle biopsy results were included,
      this parameter became the sole predictor of malignancy as other factors lost
      significance in a multivariate model. CONCLUSION: Surgical biopsy is not
      indicated in well-sampled grade 3 masses with benign needle biopsy results.
      Surgery is valuable for diagnosis or treatment of the remaining such masses
      without benign needle biopsy results.

PMID- 20691593
TI  - The role of the magnetite-based receptors in the beak in pigeon homing.
AB  - Magnetite-containing structures in the upper beak of birds have been described as
      putative magnetoreceptors [1-4], but so far, all positive evidence indicating
      their influence on behavior has come from laboratory studies using rather
      unnatural stimuli (e.g., [5-7]). Here, we demonstrate these receptors' possible
      role in a natural situation: we released pigeons with these receptors deactivated
      by a local anesthetic within and outside a magnetic anomaly, together with
      untreated control birds. Within the anomaly, the untreated birds showed unusually
      long vanishing intervals and scattered bearings, indicating confusion by the
      anomalous magnetic conditions. Anesthesia of the beak suppressed this adverse
      effect. Outside the anomaly, in contrast, the treatment had little effect. These
      findings indicate that the receptors in the beak mediate magnetic "map"
      information and that this information is normally included in the navigational
      process yet can be replaced by nonmagnetic factors at most sites.

PMID- 20691592
TI  - Sequential activation of apical and basolateral contractility drives ascidian
      endoderm invagination.
AB  - BACKGROUND: Epithelial invagination is a fundamental morphogenetic behavior that
      transforms a flat cell sheet into a pit or groove. Previous studies of
      invagination have focused on the role of actomyosin-dependent apical contraction;
      other mechanisms remain largely unexplored. RESULTS: We combined experimental and
      computational approaches to identify a two-step mechanism for endoderm
      invagination during ascidian gastrulation. During Step 1, which immediately
      precedes invagination, endoderm cells constrict their apices because of Rho/Rho
      kinase-dependent apical enrichment of 1P-myosin. Our data suggest that endoderm
      invagination itself occurs during Step 2, without further apical shrinkage, via a
      novel mechanism we call collared rounding: Rho/Rho-kinase-independent basolateral
      enrichment of 1P-myosin drives apico-basal shortening, whereas Rho/Rho-kinase
      dependent enrichment of 1P and 2P myosin in circumapical collars is required to
      prevent apical expansion and for deep invagination. Simulations show that
      boundary-specific tension values consistent with these distributions of active
      myosin can explain the cell shape changes observed during invagination both in
      normal embryos and in embryos treated with pharmacological inhibitors of either
      Rho-kinase or Myosin II ATPase. Indeed, we find that the balance of strong
      circumapical and basolateral tension is the only mechanism based on differential
      cortical tension that can explain ascidian endoderm invagination. Finally,
      simulations suggest that mesectoderm cells resist endoderm shape changes during
      both steps, and we confirm this prediction experimentally. CONCLUSIONS: Our
      findings suggest that early ascidian gastrulation is driven by the coordinated
      apposition of circumapical and lateral endoderm contraction, working against a
      resisting mesectoderm. We propose that similar mechanisms may operate during
      other invaginations.

PMID- 20691594
TI  - Biological bifocal lenses with image separation.
AB  - Almost all animal eyes follow a few, relatively well-understood functional plans.
      Only rarely do researchers discover an eye that diverges fundamentally from known
      types. The principal eye E2 of sunburst diving beetle (Thermonectus marmoratus)
      larvae clearly falls into the rarer category. On the basis of two different
      tests, we here report that it has truly bifocal lenses, something that has been
      previously suggested only for certain trilobites. Our evidence comes from (1) the
      relative contrast in images of a square wave grating and (2) the refraction of a
      narrow laser beam projected through the lens. T. marmoratus larvae have two
      retinas at different depths behind the lens, and these are situated so that each
      can receive its own focused image. This is consistent with a novel eye
      organization that possibly comprises "two eyes in one." Moreover, we find that in
      contrast to most commercial bifocal lenses, the lens of E2 exhibits asymmetry,
      which results in separation of the images both dorsoventrally and rostrocaudally
      within the layered retina. Visual contrast might thus be improved over
      conventional bifocal lenses because the unfocused version of one image is shifted
      away from the focused version of the other, an organization which could
      potentially be exploited in optical engineering.

PMID- 20691595
TI  - Bicaudal-D regulates fragile X mental retardation protein levels, motility, and
      function during neuronal morphogenesis.
AB  - The expression of the RNA-binding factor Fragile X mental retardation protein
      (FMRP) is disrupted in the most common inherited form of cognitive deficiency in
      humans. FMRP controls neuronal morphogenesis by mediating the translational
      regulation and localization of a large number of mRNA targets, and these
      functions are closely associated with transport of FMRP complexes within neurites
      by microtubule-based motors. However, the mechanisms that link FMRP to motors and
      regulate its transport are poorly understood. Here we show that FMRP is complexed
      with Bicaudal-D (BicD) through a domain in the latter protein that mediates
      linkage of cargoes with the minus-end-directed motor dynein. We demonstrate in
      Drosophila that the motility and, surprisingly, levels of FMRP protein are
      dramatically reduced in BicD mutant neurons, leading to a paucity of FMRP within
      processes. We also provide functional evidence that BicD and FMRP cooperate to
      control dendritic morphogenesis in the larval nervous system. Our findings open
      new perspectives for understanding localized mRNA functions in neurons.

PMID- 20691596
TI  - The Hydra model: disclosing an apoptosis-driven generator of Wnt-based
      regeneration.
AB  - The Hydra model system is well suited for the eludication of the mechanisms
      underlying regeneration in the adult, and an understanding of the core mechanisms
      is likely to cast light on pathways conserved in other species. Recent detailed
      analyses of the activation of the Wnt-beta-catenin pathway in bisected Hydra
      shows that the route taken to regenerate a structure as complex as the head
      varies dramatically according to the level of the amputation. When decapitation
      induces direct re-development due to Wnt3 signaling from epithelial cells, head
      regeneration after mid-gastric section relies first on Wnt3 signaling from
      interstitial cells, that undergo apoptosis-induced compensatory proliferation,
      and subsequently on activation of Wnt3 signaling in the epithelial cells. The
      relative distribution between stem cells and head progenitor cells is strikingly
      different in these two contexts, indicating that the pre-amputation homeostatic
      conditions define and constrain the route that bridges wound-healing to the re
      development program of the missing structure.

PMID- 20691597
TI  - Surface electromyography does not accurately reflect rectus femoris activity
      during gait: impact of speed and crouch on vasti-to-rectus crosstalk.
AB  - Surface EMG (sEMG) is routinely used in gait analysis laboratories to record
      rectus femoris (RF) activity during gait. This is despite the fact that the
      literature has suggested sEMG may be inaccurate for RF monitoring secondary to
      its susceptibility to crosstalk from the neighboring vasti. If true, one might
      expect this error to be exacerbated by crouch gait when vasti demand is elevated.
      The purpose of this study was to investigate the impact of vasti crosstalk on RF
      sEMG across a variety of speed (four) and crouch (four) combinations. A group of
      20 able-bodied adults were studied walking in 16 different combinations of speed
      and crouch while computerized gait analysis and EMG data were collected. RF EMG
      activity was monitored using both surface and fine wire electrodes
      simultaneously. Results showed that sEMG is affected by vasti crosstalk during
      substantial portions of both stance and swing. At the two slowest speeds tested,
      RF was not active at any point during the gait cycle, though sEMG suggested RF
      activity during some to all of stance phase. Despite sEMG indicating otherwise,
      true RF did not occur during loading response in any of the 16 conditions tested.
      During crouch at the two fastest speeds, a burst of true RF activity occurred
      during a short period of single limb stance, though sEMG incorrectly reflected RF
      activity throughout stance. Vasti-to-rectus crosstalk also occurred regularly
      during terminal swing. Surface EMG incorrectly suggests RF activity during
      portions of both stance and swing secondary to vasti crosstalk. This may lead to
      interpretation errors which could affect clinical recommendations.

PMID- 20691598
TI  - Calcium-responsive paramagnetic CEST agents.
AB  - The assessment of changes in the extracellular calcium concentration by magnetic
      resonance imaging would be a valuable biomedical research tool to monitor brain
      neuronal activity. In this perspective, we report here the synthesis of novel
      ligands consisting of tetraamide and bisamide derivatives of cyclen, L(1) and
      L(2), respectively, each bearing imino(diacetate) moieties for Ca(2+) binding.
      Yb(3+) and Eu(3+) complexes are investigated as chemical exchange saturation
      transfer (CEST) agents that respond to the presence of Ca(2+). A CEST effect is
      observed for both YbL(1) and EuL(1) complexes (B=11.7T), originating from the
      slow exchange of the amide protons and those of the coordinated water,
      respectively, whilst no CEST is detected for complexes of L(2). Upon calcium
      binding, the CEST effect decreases considerably (from 60% to 20% for YbL(1) and
      from 35% to 10% for EuL(1)). A similar variation is observed in the presence of
      Mg(2+). The affinity constants between the lanthanide complexes and the alkaline
      earth metal ions have been estimated from the variation of the CEST effect to be
      K(YbL(1)-Ca)(aff) = 8 +/- 2M(-1), K(YbL(1)-Mg)(aff) = 23 +/- 3M(-1) and K(EuL(1)
      Ca)(aff) = 10 +/- 3M(-1). These low values imply the coordination of the alkaline
      earth ions to a single iminodiacetate arm. Ca(2+)/Mg(2+) binding to the
      lanthanide complexes slows down the exchange of the amide protons on YbL(1) which
      is responsible for the diminished CEST effect. This has been evidenced by
      assessing the proton exchange rates from the dependency of the CEST effect on the
      saturation time and the saturation power, in the absence and in the presence of
      Ca(2+) and Mg(2+). The applicability of the PARACEST MRI agents for Ca(2+)
      detection has been evaluated on a 16T MRI scanner.

PMID- 20691599
TI  - Iodination of verapamil for a stronger induction of death, through GSH efflux, of
      cancer cells overexpressing MRP1.
AB  - The multidrug resistance protein 1 (MRP1), involved in multidrug resistance (MDR)
      of cancer cells, was found to be modulated by verapamil, through stimulation of
      GSH transport, leading to apoptosis of MRP1-overexpressing cells. In this study,
      various iodinated derivatives of verapamil were synthesized, including iodination
      on the B ring, known to be involved in verapamil cardiotoxicity, and assayed for
      the stimulation of GSH efflux by MRP1. The iodination, for nearly all compounds,
      led to a higher stimulation of GSH efflux. However, determination of concomitant
      cytotoxicity is also important for selecting the best compound, which was found
      to be 10-fold more potent than verapamil. This will then allow us to design
      original anti-cancer compounds which could specifically kill the resistant cancer
      cells.

PMID- 20691600
TI  - Synthesis and characterization of mitoQ and idebenone analogues as mediators of
      oxygen consumption in mitochondria.
AB  - Analogues of mitoQ and idebenone were synthesized to define the structural
      elements that support oxygen consumption in the mitochondrial respiratory chain.
      Eight analogues were prepared and fully characterized, then evaluated for their
      ability to support oxygen consumption in the mitochondrial respiratory chain.
      While oxygen consumption was strongly inhibited by mitoQ analogues 2-4 in a chain
      length-dependent manner, modification of idebenone by replacement of the quinone
      methoxy groups by methyl groups (analogues 6-8) reduced, but did not eliminate,
      oxygen consumption. Idebenone analogues 6-8 also displayed significant
      cytoprotective properties toward cultured mammalian cells in which glutathione
      had been depleted by treatment with diethyl maleate.

PMID- 20691601
TI  - Studies on preparation and photodynamic mechanism of chlorin P6-13,15-N
      (cyclohexyl)cycloimide (Chlorin-H) and its antitumor effect for photodynamic
      therapy in vitro and in vivo.
AB  - Photodynamic therapy (PDT) represents a promising method for treatment of
      cancerous tumors. The chemical and physical properties of used photosensitizer
      play key roles in the treatment efficacy. In this study, a novel photosensitizer,
      Chlorin-H [-13,15-N-(cyclohexyl)cycloimide] which displayed a characteristic long
      wavelength absorption peak at 698nm was synthesized. Following flash photolysis
      with 355nm laser, Chlorin-H is potent to react with O(2) and then produce
      (1)O(2). This finding indicates that Chlorin-H takes its effects through type II
      mechanism in PDT. Generally, Chlorin-H is localized in mitochondria and nucleus
      of cell. After light irradiation with 698nm laser, it can kill many types of
      cell, inhibit cell proliferation and colony formation, suppress cancer cell
      invasiveness and trigger apoptosis via the mitochondrial pathway in A549 cells in
      vitro. In addition, Chlorin-H-PDT can destroy A549 tumor in nude mice and a
      necrotic scab was formed eventually. The expression levels of many genes which
      regulated cell growth and apoptosis were determined by RT-PCR following Chlorin-H
      PDT. The results showed that it either increased or decrease. Among which, the
      expression level of TNFSF13, a member of tumor necrosis factor superfamily,
      increased significantly. Silencing of TNFSF13 caused by RNA interference
      decreased the susceptibility of A549 cells to Chlorin-H-PDT. In general, Chlorin
      H is an effective antitumor photosensitizer in vitro and in vivo and is worthy of
      further study as a new drug candidate. TNFSF13 will be an important molecular
      target for the discovery of new photosensitizers.

PMID- 20691602
TI  - Accuracy and precision of (238)Pu determination at fg level by alpha spectrometry
      using (239)Pu and (240)Pu amount analyzed by ICP-MS.
AB  - The accuracy and precision of the determination of (238)Pu amount at the fg (mBq)
      level by a combination of alpha spectrometry and inductively coupled plasma mass
      spectrometry (ICP-MS) were studied using a standard reference material (CRM 137
      Plutonium [corrected] Isotopic Standard, National Bureau of Standards,
      Washington, D.C., USA). The activity of (238)Pu was calculated from the amount of
      (239)Pu and (240)Pu obtained by isotope dilution method and ICP-MS combined with
      the intensity ratio of (238)Pu/(239,240)Pu obtained by alpha spectrometry without
      adding spike. The results show that approximately 130 fg of (238)Pu can be
      analyzed within an accuracy of 7% bias and with 5-12% of total uncertainty. The
      examined analytical procedure was applied to the quantitative analysis of (238)Pu
      in water samples representing Safeguards inspection samples. The combination of
      alpha spectrometry and ICP-MS is useful for quantitative and isotopic analysis in
      low-level Pu samples. Also the method leads to improving the accuracy of (238)Pu
      determination because efficiency calibration is not necessary for alpha
      spectrometry.

PMID- 20691603
TI  - New measurement of excitation functions for (d,x) reactions on (nat)Mo with
      special regard to the formation of (95m)Tc, (96m+g)Tc, (99m)Tc and (99)Mo.
AB  - Cross-sections for the deuteron-induced reactions on natural molybdenum leading
      to (93m)Tc, (93m+g)Tc, (94)Tc, (94m)Tc, (95)Tc, (95m)Tc, (96m+g)Tc, (99m)Tc,
      (99)Mo, (101)Mo, (90m+g)Nb, (92m)Nb, (95)Nb and (89m+g)Zr were measured in the
      energy range 3.0-19.6 MeV on the cyclotron U-120 M in the Institute of Nuclear
      Physics AS CR. Special attention was paid to excitation functions and thick
      target yields for the formation of (95m)Tc, a suitable tracer for (99)Tc, of
      (96m+g)Tc, which might be used as a beam monitor, and of (99m)Tc and (99)Mo, the
      most widespread radionuclide generator pair in nuclear medicine. If appropriate,
      obtained data are compared with the heretofore published cross-sections.

PMID- 20691604
TI  - Transapical aortic valve implantation after previous heart surgery.
AB  - OBJECTIVE: Transcatheter aortic valve implantation is a new method for the
      treatment of very-high-risk patients with aortic valve stenosis. Particularly in
      patients who have had previous cardiac surgery, the operative risk can be
      reduced. Nevertheless, this new procedure has some potential risks in these
      patients, due to the increased danger of endocarditis and in view of potential
      graft damage after previous bypass grafting or prosthesis damage after previous
      valve replacement, caused by wire manipulation or valve liberation. METHODS:
      Between April 2008 and January 2010, 198 consecutive patients underwent
      transapical aortic valve implantation. Group A consisted of 158 patients without
      previous heart surgery and group B had 40 patients with previous heart operation
      (23 coronary artery bypass grafting, three aortic valve replacements, two mitral
      valve repairs, one replacement, and 11 combined operations). Although patients in
      group B (75 +/- 11) were significantly younger than the ones in group A (80 +/-
      8) (p = 0.003), the preoperative risk score was significantly higher in group B
      (group A - the European System for Cardiac Operative Risk Evaluation (EuroSCORE):
      37 +/- 18%; the Society of Thoracic Surgeons (STS) mortality score: 21 +/- 16;
      group B - EuroSCORE: 53 +/- 21%; STS mortality score: 29 +/- 18) (p < 0.001, p =
      0.006). RESULTS: The technical success rate was 99.5% (157/158) in group A and
      100% (40/40) in group B. One patient in group A developed an annulus rupture. The
      postoperative echocardiographic examinations showed low transvalvular gradient
      due to the special design of the valve, without differences between the two
      groups. The 30-day mortality was 6.9% in group A and 5.0% in group B, and the 1
      year survival was 77% and 74% in group A and group B, respectively
      (nonsignificant). CONCLUSIONS: Transcatheter valve implantation can be performed
      successfully after previous heart surgery. Particular care should be taken to
      achieve optimal valve position and not to damage grafts or prosthetic valves
      during manipulation with guide wires or valve positioning.

PMID- 20691605
TI  - Gas-phase meerwein reaction of epoxides with protonated acetonitrile generated by
      atmospheric pressure ionizations.
AB  - Ethylnitrilium ion can be generated by protonation of acetonitrile (when used as
      the LC-MS mobile phase) under the conditions of atmospheric pressure ionizations,
      including electrospray ionization (ESI) and atmospheric pressure chemical
      ionization (APCI) as well as atmospheric pressure photoionization (APPI).
      Ethylnitrilium ion (CH(3)-C=N+H and its canonical form CH(3)-C+=NH) is shown to
      efficiently undergo the gas-phase Meerwein reaction with epoxides. This reaction
      proceeds by the initial formation of an oxonium ion followed by three-to-five
      membered ring expansion via an intramolecular nucleophilic attack to yield the
      Meerwein reaction products. The density functional theory (DFT) calculations at
      the B3LYP/6-311+G(d,p) level show that the gas-phase Meerwein reaction is
      thermodynamically favorable. Collision-induced dissociation (CID) of the Meerwein
      reaction products yields the net oxygen-by-nitrogen replacement of epoxides with
      a characteristic mass shift of 1 Da, providing evidence for the cyclic nature of
      the gas-phase Meerwein reaction products. The gas-phase Meerwein reaction offers
      a novel and fast LC-MS approach for the direct analysis of epoxides that might be
      of genotoxic concern during drug development. Understanding and utilizing this
      unique gas-phase ion/molecule reaction, the sensitivity and selectivity for
      quantitation of epoxides can be enhanced.

PMID- 20691606
TI  - Use of yttrium-90 microspheres in patients with advanced hepatocellular carcinoma
      and portal vein thrombosis.
AB  - PURPOSE: Patients with portal vein thrombosis (PVT) and hepatocellular carcinoma
      (HCC) have limited treatment options because of increased disease burden and
      diminished hepatic perfusion. Yttrium-90 ((90)Y) microspheres may be better
      tolerated than chemoembolization in these patients. The present study reviews the
      safety and efficacy of (90)Y microspheres in HCC with major PVT. MATERIALS AND
      METHODS: A retrospective review of HCC with main (n = 10) or first-branch (n =
      12) PVT treated with (90)Y microspheres (N = 22) was conducted. Cancer of the
      Liver Italian Program (CLIP) scores ranged from 2 to 5, with 18% of patients
      having a score of 4 or greater. Imaging response at 8-12 was based on Response
      Evaluation Criteria In Solid Tumors. Overall survival (OS) was estimated by the
      Kaplan-Meier method. RESULTS: A total of 32 microsphere treatments (26 glass, six
      resin) were administered to 22 patients. Common grade 1/2 toxicities included
      abdominal pain (38%), nausea (28%), and fatigue (22%). Four posttreatment
      hospitalizations occurred, all less than 48 hours in duration. One death occurred
      10 days after therapy. The partial response rate was 8% and progressive disease
      was seen in 42% of patients. Stable disease was achieved in 50% of treatments.
      Median OS was 7 months from initial treatment. Patients with Child-Pugh class A
      disease had a median OS of 7.7 months; those with class B/C disease had an OS of
      2.7 months (P = .01). Median OS for patients with CLIP scores of 2/3 was 7
      months, versus 1.3 months for those with scores of 4/5 (P = .04). CONCLUSIONS:
      Yttrium-90 microspheres are tolerated in patients with HCC and major PVT.
      Compared with chemoembolization, rates of severe adverse events appear low.
      Radiographic response rates are low. The median OS of 7 months is promising and
      warrants further study versus systemic therapy.

PMID- 20691607
TI  - Modified stent-supported coil embolization for treatment of a splenic artery
      pseudoaneurysm.
AB  - A patient presented 2 weeks after distal pancreatectomy and splenectomy with
      increased bloody output from his surgical drain. Catheter angiography found an
      enlarging splenic artery stump pseudoaneurysm. During the procedure, there was
      concern that nontarget embolization may occur, given the short splenic artery
      remnant. Pseudoaneurysm thrombosis was subsequently achieved using a variation of
      stent-supported coil embolization. At 3-month follow-up, the patient had no
      recurrent bleeding from the surgical site. Although this technique has been
      described in the treatment of neurovascular and renal artery aneurysms, it is
      applicable to, and readily adapted for, use in visceral arterial procedures.

PMID- 20691608
TI  - Late stent fractures after endoluminal treatment of ostial supraaortic trunk
      arterial occlusive lesions.
AB  - PURPOSE: Percutaneous catheter-based treatment of supraaortic trunk arterial
      occlusive lesions obviates the need for extraanatomic bypass or median
      sternotomy. Although early results have been encouraging, late outcomes have yet
      to be defined. Reported are long-term outcomes of supraaortic trunk stent
      placement with particular attention to structural failures. MATERIALS AND
      METHODS: This was a retrospective review of 27 ostial supraaortic trunk lesions
      managed with balloon-expandable or self-expandable stents. Treated vessels were
      innominate (n = 9), common carotid (n = 8), and subclavian (n = 10). Access to
      the target lesion was achieved either antegrade via the femoral artery (n = 13),
      retrograde through the brachial artery (n = 2), or through a cutdown on the
      common carotid artery (n = 12). Restenosis and stent integrity were detected with
      duplex imaging, computed tomography, conventional arteriography, and plain
      radiography. Mean follow-up time is 34 months. RESULTS: Mean age was 68 years
      (eight men and 19 women), and mean stenosis was 85%. Preprocedural symptoms,
      including stroke, transient ischemic attack, arm fatigue, digital ischemia, and
      angina were present in 85% (23 of 27) of the group. At 30 days, there were no
      deaths, myocardial infarctions, or strokes. During follow-up, three type IV stent
      fractures in the innominate were detected as well as two midbody stent crush
      deformities with significant restenosis (one innominate and one common carotid).
      All stent failures were identified in heavily calcified lesions. CONCLUSIONS:
      Endoluminal stent placement in supraaortic trunk lesions is a viable early
      solution; however, mid- to long-term restenosis caused by bare metal fatigue and
      fractures, particularly in cases of calcified innominate artery lesions, are a
      worrisome finding.

PMID- 20691609
TI  - Zone I gunshot neck injury treated with common carotid and esophageal stent
      grafts.
AB  - Management of zone I gunshot injuries to the neck is controversial. Endovascular
      and endoscopic therapies are appealing minimally invasive alternatives, but they
      are still evolving. This case report demonstrates effective stent grafting of an
      arterial and an esophageal zone I neck injury after a civilian gunshot.

PMID- 20691610
TI  - Effect of transjugular intrahepatic portosystemic shunt placement on renal
      function: a 7-year, single-center experience.
AB  - PURPOSE: Transjugular intrahepatic portosystemic shunt (TIPS) creation has been
      shown to improve renal function in small series of patients with hepatorenal
      syndrome. The present study examined the effect of TIPS creation on renal
      function in a large series of patients undergoing TIPS creation who had varying
      degrees of baseline renal function. MATERIALS AND METHODS: All de novo TIPS
      creations during a 7-year period at a single institution were retrospectively
      reviewed regardless of indication. Pre- and postprocedural laboratory values were
      obtained and used to calculate Model for End-Stage Liver Disease (MELD) scores
      and glomerular filtration rates. Subanalysis was performed based on degree of
      renal insufficiency and indication for the procedure. RESULTS: A total of 201
      successful conventional TIPS procedures were identified. Of those, 72 patients
      were excluded for lack of follow-up, death during the same hospitalization, lack
      of TIPS function, or end-stage renal failure requiring dialysis before TIPS
      creation, leaving 129 procedures. Patients with preprocedural creatinine levels
      of 1.2-1.9 mg/dL (n = 45) showed an improvement in mean creatinine from 1.5 to
      1.1 mg/dL (P < 10(-12)) and patients with preprocedure creatinine levels greater
      than 2.0 mg/dL (n = 21) showed an improvement from 2.8 to 1.5 mg/dL (P < 10(-5)).
      MELD scores decreased in patients with creatinine levels greater than 2.0 mg/dL
      from 22.1 to 19.2 (P < 0.005) but increased in all other patient groups. Amount
      of iodinated contrast medium administered did not affect creatinine level
      changes. CONCLUSIONS: TIPS creation improves renal dysfunction in chronic liver
      disease. Patients with poorer renal function benefit the most from TIPS creation.

PMID- 20691612
TI  - Outcomes of heart transplantation using donor hearts from infants with sudden
      infant death syndrome.
AB  - BACKGROUND: Uncertainty exists whether hearts from infants who have died of
      sudden infant death syndrome (SIDS) are acceptable for transplantation because
      the mechanism of death in SIDS remains unclear. We analyzed post-transplant
      outcomes in infants who received a heart from a donor where SIDS was the primary
      cause of brain death. METHODS: This retrospective multicenter cohort study used
      data from the Organ Procurement and Transplant Network (OPTN). All infants aged <
      12 months undergoing heart transplant between 1994 and 2008 were included. A Cox
      proportional hazards model was used to determine whether donor SIDS was
      independently associated with post-transplant graft loss (death or retransplant).
      RESULTS: During the study period, 66 of 1033 infants (6.4%) who underwent heart
      transplant received an allograft from a SIDS donor. These infants were similar to
      the remaining infants with respect to age, diagnosis, blood type, and invasive
      support. In multivariable analysis, graft loss was associated with congenital
      heart disease (hazard ratio [HR], 1.6; 95% confidence interval [CI], 1.2-2.1),
      ventilator (HR, 1.4; 95% CI, 1.1-1.9), and extracorporeal membrane oxygenation
      support (HR, 3.0; 95% CI, 2.2-4.3), but not donor SIDS (HR, 1.0; 95% CI, 0.6
      1.5), suggesting graft survival in SIDS-donor heart recipients was similar to the
      remaining infants. Primary causes of post-transplant death in infants receiving
      SIDS-donor hearts and the remaining infants were similar. CONCLUSIONS: Graft
      survival was similar in infants who received SIDS-donor hearts compared with
      those who received hearts from donors who died of other causes. There was no
      increase in incidence of non-rejection-related cardiac deaths after transplant in
      these children.

PMID- 20691611
TI  - Synergistic effect of antibodies to human leukocyte antigens and defensins in
      pathogenesis of bronchiolitis obliterans syndrome after human lung
      transplantation.
AB  - BACKGROUND: This study aims to determine the role of antibodies to donor
      mismatched human leukocyte antigen (HLA) developed during the post-transplant
      period in inducing defensins and their synergistic role in the pathogenesis of
      chronic rejection, bronchiolitis obliterans syndrome (BOS), after human lung
      transplantation (LTx). METHODS: Bronchoalveolar lavage (BAL) and serum from 21
      BOS+ LTx patients were assayed for beta-defensins human neutrophil peptides (HNP)
      1-3 (enzyme-linked immunosorbent assay [ELISA]) and anti-HLA antibodies (Luminex,
      Luminex Corp, Austin, TX). Human airway epithelial cells (AEC) were treated with
      anti-HLA antibodies, HNP-1/2, or both, and the levels of beta-defensin were
      measured by ELISA. Using a mouse model of obliterative airway disease induced by
      anti-major histocompatibility (MHC) class-I antibodies, we quantitatively and
      qualitatively determined neutrophil infiltration by myeloperoxidase (MPO)
      staining and activity by MPO assay, and defensin levels in the BAL. RESULTS: In
      human LTx patients, higher defensin levels correlated with presence of
      circulating anti-HLA antibodies (p < 0.05). AEC treated with anti-HLA antibodies
      or HNP-1/2, produced beta-defensin with synergistic effects in combination (612
      +/- 06 vs 520 +/- 23 pg/ml anti-HLA antibody, or 590 +/- 10 pg/ml for HNP
      treatment; p < 0.05). Neutrophil numbers (6-fold) and activity (5.5-fold) were
      higher in the lungs of mice treated with anti-MHC antibodies vs control. A 2-fold
      increase in alpha-defensin and beta-defensin levels was also present in BAL on
      Day 5 after anti-MHC administrations. CONCLUSIONS: Anti-HLA antibodies developed
      during the post-transplant period and alpha-defensins stimulated beta-defensin
      production by epithelial cells, leading to increased cellular infiltration and
      inflammation. Chronic stimulation of epithelium by antibodies to MHC and
      resulting increased levels of defensins induce growth factor production and
      epithelial proliferation contributing to the development of chronic rejection
      after LTx.

PMID- 20691613
TI  - ROC in animals: uncovering the neural substrates of recollection and familiarity
      in episodic recognition memory.
AB  - It is a consensus that familiarity and recollection contribute to episodic
      recognition memory. However, it remains controversial whether familiarity and
      recollection are qualitatively distinct processes supported by different brain
      regions, or whether they reflect different strengths of the same process and
      share the same support. In this review, I discuss how adapting standard human
      recognition memory paradigms to rats, performing circumscribed brain lesions and
      using receiver operating characteristic (ROC) methods contributed to solve this
      controversy. First, I describe the validation of the animal ROC paradigms and
      report evidence that familiarity and recollection are distinct processes in
      intact rats. Second, I report results from rats with hippocampal dysfunction
      which confirm this finding and lead to the conclusion that the hippocampus
      supports recollection but not familiarity. Finally, I describe a recent study
      focusing on the medial entorhinal cortex (MEC) that investigates the contribution
      of areas upstream of the hippocampus to recollection and familiarity.

PMID- 20691614
TI  - Follicular B cell trafficking within the spleen actively restricts humoral immune
      responses.
AB  - Follicular (FO) and marginal zone (MZ) B cells are maintained in distinct
      locations within the spleen, but the genetic basis for this separation is still
      enigmatic. We now report that B cell sequestration requires lineage-specific
      regulation of migratory receptors by the transcription factor Klf2. Moreover,
      using gene-targeted mice we show that altered splenic B cell migration confers a
      significant in vivo gain-of-function phenotype to FO B cells, including the
      ability to quickly respond to MZ-associated antigens and pathogens in a T cell
      dependent manner. This work demonstrates that in wild-type animals, naive FO B
      cells are actively removed from the MZ, thus restricting their capacity to
      respond to blood-borne pathogens.

PMID- 20691616
TI  - Validation and reference values of automated bone age determination for four
      ethnicities.
AB  - RATIONALE AND OBJECTIVES: Bone age (BA) rating is associated with a considerable
      rater variability, which would be eliminated with an automated computerized
      method. The aim of the study was to validate the BoneXpert method, an automated
      determination of BA, in American children of four ethnicities. MATERIALS AND
      METHODS: The study is based on a publicly available database of hand x-rays of
      healthy children, established in a previous, National Institutes of Health-funded
      study. Radiographs of the left hand were recorded between 1993 and 2006 in Los
      Angeles, including 1100 images with two independent manual BA ratings and 280
      additional images for which the manual ratings were not used. Images were evenly
      split between Caucasian, African American, Hispanic, and Asian children, and the
      age range was 0-18.99 years. RESULTS: The automated method analyzed all images
      with BA >2.5 years for boys and >2 years for girls. The root-mean-square (RMS)
      error between the two manual ratings was 0.63 years, whereas the RMS deviation
      between the automated BA and the average of the two manual ratings was 0.61
      years. The mean BA minus age was computed versus age for each sex and ethnicity.
      The largest deviation from zero was seen for Hispanic and Asian children older
      than 12 years, who were about 1 year advanced relative to the Greulich and Pyle
      standard. CONCLUSION: The automated method can analyze images of all ethnicities
      within a BA range of 2.5-17 years for boys and 2-15 years for girls, and can
      therefore eliminate the problem with rater variability in BA rating.

PMID- 20691615
TI  - Follicular helper T cell differentiation requires continuous antigen presentation
      that is independent of unique B cell signaling.
AB  - Effective humoral immunity depends on the support of B cell responses by T
      follicular helper (Tfh) cells. Although it has been proposed that Tfh cell
      differentiation requires T-B interactions, the relative contribution of specific
      populations of Ag-presenting cells remains unknown. We employed three independent
      strategies that compromised interactions between CD4(+) T cells and activated B
      cells in vivo. Whereas the expansion of CD4(+) T cells was relatively unaffected,
      Tfh cell differentiation was completely blocked in all scenarios. Surprisingly,
      augmenting antigen presentation by non-B cells rescued Tfh cell differentiation,
      as determined by surface phenotype, gene expression, and germinal center
      localization. We conclude that although Ag presentation by responding B cells is
      typically required for the generation of Tfh cells, this does not result from the
      provision of a unique B cell-derived signal, but rather because responding B
      cells rapidly become the primary source of antigen.

PMID- 20691617
TI  - Effect of hospital and surgeon volume on patient outcomes following treatment of
      abdominal aortic aneurysms: a systematic review.
AB  - OBJECTIVES: This systematic review assessed the efficacy of centralisation for
      the treatment of unruptured and ruptured abdominal aortic aneurysms. Patient
      outcomes achieved by low and high volume hospitals/surgeons, including morbidity,
      mortality and length of hospital stay, were used as proxy measures of efficacy.
      DESIGN: Systematic review was designed to identify, assess and report on peer
      reviewed articles reporting outcomes from unruptured and ruptured abdominal
      aortic aneurysms. No language restriction was placed on the databases searched.
      MATERIALS: Only peer-reviewed journals articles were included. METHODS: To ensure
      the contemporary nature of this review, only studies published between January
      1997 and June 2007 were sought. Studies were included if they reported on at
      least one volume type and patient outcome. RESULTS: Twenty two studies were
      included in this review. In the majority of group assessments, the number of
      studies reporting statistical significance was similar to the number of studies
      reporting no statistical significance. CONCLUSION: The paucity of studies
      reporting statistically significant results demonstrates that although this
      evidence exists, its potential to be overstated must also be taken into account
      when drawing conclusions as to its efficacy for twenty first century healthcare
      systems.

PMID- 20691618
TI  - Abdominal aortic aneurysm surgery in renal, cardiac and hepatic transplant
      recipients.
AB  - With advancements in transplantation and improved long-term allograft survival,
      the once rare clinical scenario of an abdominal aortic aneurysm (AAA) in a
      patient with a functioning allograft has become much more frequent. In transplant
      recipients, AAA repair has the potential to cause irreversible ischaemic injury
      to the transplanted organ. Different case series and case reports have mentioned
      a variety of techniques to offer protection to the transplanted organs during
      aneurysm repair such as cold perfusion, shunting, temporary surgical bypass and
      extracorporeal circuits etc. Critical review of these adjuncts seems to suggest
      that that they do not give any better results than just using a "clamp and go"
      approach. Endovascular aneurysm repair (EVAR) may offer some advantages for
      transplant patients who have suitable anatomy for endovascular stent deployment.
      In addition to these surgical techniques, various aspects of medical management
      for renal, cardiac and hepatic transplant recipients undergoing AAA repair are
      discussed.

PMID- 20691619
TI  - Comment on "PTFE bypass to below-knee arteries: distal vein collar or not? A
      prospective randomised multicentre study".

PMID- 20691620
TI  - Iron metabolism gene expression in human skeletal muscle.
AB  - Little is known about iron metabolism in skeletal muscle while hepatic iron
      metabolism is well understood. The aim of this study is to compare the iron
      metabolism gene expression profile in skeletal muscle and the liver in humans.
      Muscle and hepatic biopsies from six normal individuals were acquired. Twelve
      genes involved in iron metabolism( import, storage, export) were selected to be
      studied. Reverse transcriptase polymerase chain reaction (RT-PCR) was performed
      in order to determine the expression profile in skeletal muscle and compare it to
      the one from the liver. Semi-quantification of the gene expression in the studied
      tissues was performed by densitometric analysis (DA). The results were expressed
      relative to the percentage of the beta-actin gene. Fine analysis was performed by
      real-time PCR (q-PCR) quantification for the genes that their expression
      presented a difference of more than 20% in the 2 tissues in the first applied
      densitometric analysis. Most of the studied genes, HJV, TFR1, HFE, DMT1,
      DMT1nonIRE, NGAL, HEPH, IREG1, FTH1 were well expressed (>70% of beta-actin) in
      skeletal muscle . HAMP, CP, and TFR2 were absent or minimally expressed (<10% of
      beta-actin) in skeletal muscle while they were well expressed in liver. HJV and
      Heph were found to have higher expression in skeletal muscle (SM) compared to
      liver (L) (SM/L=2.65 +/- 1.1(p<0.05) and SM/L=1.5 +/- 0.06(p<0.05 respectively in
      q-PCR). The relative expressions of the studied genes in both tissues and their
      relative contribution in iron homeostasis in different pathways are discussed.

PMID- 20691621
TI  - Hemoglobin H disease due to a de novo mutation at the alpha2-globin gene and an
      inherited common alpha-thalassemia deletion found in a Chinese boy.
AB  - Hemoglobin (Hb) H disease is a moderate form of alpha-thalassemia resulting from
      various genetic defects. A novel frameshift mutation cd 43/44(-C) at the alpha2
      globin gene was identified in a Chinese boy with hemoglobin H disease by
      sequencing. The proband's mother carries a common alpha-thalassemia deletion
      while his father was normal both in the hematological phenotype and alpha-globin
      genotype, which suggested that it occurred as a de novo mutation. Molecular
      studies revealed a compound heterozygote for the Southeast Asian alpha
      thalassemia deletion and this novel spontaneous mutation (-/alpha(T)alpha) and
      the patient exhibited the clinical manifestation of classic hemoglobin H disease.
      Based on the results of excluding the possibility of a somatic mosaicism of a
      point mutation in the alpha2-globin gene, we progress that this de novo single
      base deletion should have arisen during the spermatogenic process or earlier
      embryonic stage. The present study provides information in determining a
      supplementary model of inheritance for alpha-thalassemia, which should be useful
      in genetic counseling.

PMID- 20691622
TI  - JAK2 46/1 haplotype seems not to be associated with lower limb deep venous
      thrombosis.

PMID- 20691623
TI  - The effects of hypertonic dehydration changes on renal function and arginine
      vasopressin in the horse during pulling exercises.
AB  - This study investigated the effect of hypertonic dehydration on exercise in
      horses. Valencian draft horses (n=43) with hypertonic dehydration following water
      and food deprivation and competing in pulling events (COM), were compared to
      euhydrated horses (n=11) during a pulling exercise test (PET). Both groups were
      divided into bodyweight (BW) categories A (<=350 kg), B (351-450 kg), and C
      (>=451 kg), and pulled 2, 2.25, and 2.5 times BW, respectively. Exercise duration
      (ED) was 1.3+/-0.8 min. Heart rate, respiratory rate, rectal temperature and
      blood samples were taken at rest, after exercise, and during the first 30 min of
      passive recuperation. The only difference between BW categories was the packed
      cell volume (PCV), which was higher after exercise in COM horses in group A
      (52.7+/-2.3%) than in B (49.3+/-3.4%), so the data for the three BW categories
      were combined. The COM horses had higher levels of resting plasma proteins,
      albumin, urea, creatinine, sodium and arginine vasopressin (AVP) than PET horses.
      Exercise induced significantly greater (P<0.05) increases in heart rate and
      lactate in the COM horses. AVP was negatively correlated with ED and positively
      with PCV, plasma proteins, albumin, urea, and sodium. Peak AVP concentrations did
      not differ in the two groups.

PMID- 20691624
TI  - Comparative efficacy of three commercial PCV2 vaccines in conventionally reared
      pigs.
AB  - The aim of this study was to compare the efficacy of three commercial porcine
      circovirus type 2 (PCV2) vaccines. Twenty 3-week old pigs were injected with one
      of three different vaccines, A, B, C, or were unvaccinated controls. Pigs in
      group A were given a second dose at 6 weeks of age according to the
      manufacturer's protocol. Antibody titers in all pigs declined gradually, but
      increased sharply by 22 weeks of age. Viremia in the three vaccinated groups at
      22 weeks of age was significantly less than in the control group. The average
      daily gains of pigs in groups A-C, and in controls were 0.81 +/- 0.03, 0.80 +/-
      0.05, 0.78 +/- 0.04, and 0.74 +/- 0.05 kg, respectively. It was concluded that
      PCV2 vaccine reduced viremia and improved weight gain, but differences in weight
      gain among vaccinated groups were not statistically significant.

PMID- 20691625
TI  - Investigating decisions to absent from work with low back pain: a study combining
      patient and GP factors.
AB  - BACKGROUND: Determinants of who is and who is not sick-listed following an
      initial consultation for LBP have received little attention. Both patient and
      practitioner factors are suggested to be predictive but the interaction has not
      been investigated. AIMS: To investigate patient and GP factors which determine
      sickness certification for low back pain. METHODS: Thirty-four General
      Practitioners recruited 126 patients into the study. Patients completed
      questionnaires including work status; LBP history; pain; disability, mood and
      beliefs about back pain. RESULTS: No differences between sick-listed and non-sick
      listed groups were observed for age; back beliefs; anxiety; depression or fear
      avoidance beliefs about physical activity. Those sick-listed demonstrated greater
      pain intensity (p=0.009); perceived disability (p=0.040); and fear-avoidance
      beliefs about work (p<0.000). Regression analyses for GP factors only; patient
      factors only; and combined GP and patient factors were performed. The ability of
      the models to correctly classify subjects ranged from 69% for GP variables only;
      75% for patient variables only and 82% for the combined model. DISCUSSION:
      Whether a sickness certificate is issued following an initial consultation for
      LBP was best explained by combining GP and patient factors. The implications for
      this in managing absence from work are discussed.

PMID- 20691626
TI  - Development of highly predictive 3D-QSAR CoMSIA models for anthraquinone and
      acridone derivatives as telomerase inhibitors targeting G-quadruplex DNA
      telomere.
AB  - G-quadruplex structures of DNA represent a potentially useful target for
      anticancer drugs. Telomerase enzyme, involved in immortalization of cancer cells
      is inhibited by stabilization of G-quadruplex at the ends of chromosomes.
      Anthraquinone and acridone derivatives are promising G-quadruplex ligands as
      telomerase inhibitors. So far, optimization of these ligands remained hampered
      due to the lack of creditable quantitative structure-activity relationships. To
      understand the structural basis of anthraquinone and acridone derivatives, a
      predictive 3D-QSAR model has been developed for the first time for telomerase
      inhibitory activity of G4 ligands, employing comparative molecular similarity
      indices analysis (CoMSIA). Considering the proposition that the basic nitrogens
      in these compounds should exist in protonated form at physiological pH the
      protonated forms of the reported compounds were analyzed and investigated. The
      QSAR model from conformational template Conf1 exhibited best correlative and
      predictive properties. The actual predictive abilities of the QSAR model were
      thoroughly validated through an external validation test set of compounds. The
      statistics indicate a significantly high prediction power of the best model
      (r(2), 0.721), supporting the proposed molecular mechanism of DNA G-quadruplex
      ligands.

PMID- 20691627
TI  - Age adjusting severity scores for Anderson-Fabry disease.
AB  - Anderson-Fabry Disease (AFD) is a life-threatening X-linked lysosomal storage
      disorder, caused by a deficiency of alpha galactosidase A. The disease affects
      males and females, and may present in childhood or adulthood. In the absence of a
      biomarker of disease burden or therapeutic response, scoring systems based on
      clinical manifestations, have been developed. Such global scores e.g. the Mainz
      Severity Score Index (MSSI) are confounded by the natural history of disease that
      deteriorates with age, making comparisons across age groups invalid. In this
      study the baseline MSSI, as adapted for data collected in the Fabry Outcome
      Survey (FOS) database (FOS-MSSI), was calculated for 655 females and 617 males
      with confirmed AFD. Using an ANCOVA model, equations for the predicted FOS-MSSI
      based on age were derived for males and females from data where patients from the
      UK or outside Europe were excluded. The initially excluded patients were used for
      validation. The predicted severity scores of UK and non-Europe-cohorts of adult
      and paediatric patients were found to follow the model produced for the European
      cohort thereby providing validation of the methodology. Deviation of the actual
      FOS-MSSI from the predicted was calculated and termed the age-adjusted score.
      Examples of the use of the age-adjusted score in individual patients, in
      comparison of mutations and in investigation of early factors which may impact on
      later severity of Fabry disease are given. This validated age and gender adjusted
      scoring system allows the comparison of disease severity in different subgroups
      such as genotypes without age or sex as confounding factors.

PMID- 20691628
TI  - UPF1 association with the cap-binding protein, CBP80, promotes nonsense-mediated
      mRNA decay at two distinct steps.
AB  - Nonsense-mediated mRNA decay (NMD) is an mRNA surveillance mechanism that in
      mammals generally occurs upon recognition of a premature termination codon (PTC)
      during a pioneer round of translation. This round involves newly synthesized mRNA
      that is bound at its 5' end by the cap-binding protein (CBP) heterodimer CBP80
      CBP20. Here we show that precluding the binding of the NMD factor UPF1 to CBP80
      inhibits NMD at two steps: the association of SMG1 and UPF1 with the two
      eukaryotic release factors (eRFs) during SURF complex formation at a PTC, and the
      subsequent association of SMG1 and UPF1 with an exon-junction complex. We also
      demonstrate that UPF1 binds PTC-containing mRNA more efficiently than the
      corresponding PTC-free mRNA in a way that is promoted by the UPF1-CBP80
      interaction. A unifying model proposes a choreographed series of protein-protein
      interactions occurring on an NMD target.

PMID- 20691629
TI  - Survey of medication usage patterns among essential tremor patients: movement
      disorder specialists vs. general neurologists.
AB  - BACKGROUND: Although small treatment trials have examined the efficacy of front
      line medications in tremor reduction in essential tremor (ET), an overall survey
      of pharmacological management has not been undertaken in a large sample of ET
      cases. OBJECTIVES: To conduct a survey of medication usage among several hundred
      ET patients. METHODS: A computerized database at the Neurological Institute of
      New York was used to identify 223 ET patients cared for by movement disorder
      neurologists and 37 cared for by general neurologists. Each had been seen one or
      more times within past five years. Lifetime treatment data were abstracted from
      clinical records. RESULTS: One-hundred-sixty-three (73.1%) of 223 patients cared
      for by movement disorder neurologists had taken medication for ET during their
      lifetime; 53/163 (32.5%) had taken >=4 medications; 31/163 (19.0%) had taken >=5
      medications; and 3 (1.8%), >=10 medications. Nearly three-quarters (158/223
      [70.9%]) had taken primidone or propranolol, yet 89/158 (56.3%) had discontinued
      both. Among 11 patients who had undergone ET surgery, the mean number of ET
      medications tried was 6.0 +/- 2.8 (range = 3-12). Medication usage by general
      neurologists was less than by movement disorder specialists (p < 0.001). One
      third of general neurologists' patients (14/37 [37.8%]) had taken primidone or
      propranolol at some point and 6/14 (42.9%) had discontinued both. CONCLUSIONS: In
      this large survey, a substantial proportion of ET patients failed treatment with
      both front-line medications. Among patients seeing movement disorder specialists,
      the number of medications they had had to try was sizable. These data demonstrate
      the limitations of current pharmacological options for ET.

PMID- 20691630
TI  - The association between the geography of fast food outlets and childhood obesity
      rates in Leeds, UK.
AB  - OBJECTIVE: To analyse the association between childhood overweight and obesity
      and the density and proximity of fast food outlets in relation to the child's
      residential postcode. DESIGN: This was an observational study using individual
      level height/weight data and geographic information systems methodology. SETTING:
      Leeds in West Yorkshire, UK. This area consists of 476 lower super-output areas.
      PARTICIPANTS: Children aged 3-14 years who lived within the Leeds metropolitan
      boundaries (n=33,594). MAIN OUTCOME MEASURES: The number of fast food outlets per
      area and the distance to the nearest fast food outlet from the child's home
      address. The weight status of the child: overweight, obese or neither. RESULTS:
      27.1% of the children were overweight or obese with 12.6% classified as obese.
      There is a significant positive correlation (p<0.001) between density of fast
      food outlets and higher deprivation. A higher density of fast food outlets was
      significantly associated (p=0.02) with the child being obese (or
      overweight/obese) in the generalised estimating equation model which also
      included sex, age and deprivation. No significant association between distance to
      the nearest fast food outlet and overweight or obese status was found.
      CONCLUSIONS: There is a positive relationship between the density of fast food
      outlets per area and the obesity status of children in Leeds. There is also a
      significant association between fast food outlet density and areas of higher
      deprivation.

PMID- 20691631
TI  - Primary care randomized clinical trial: manual therapy effectiveness in
      comparison with TENS in patients with neck pain.
AB  - This study investigated effectiveness of manual therapy (MT) with transcutaneous
      electrical nerve stimulation (TENS) to reduce pain intensity in patients with
      mechanical neck disorder (MND). A randomized multi-centered controlled clinical
      trial was performed in 12 Primary Care Physiotherapy Units in Madrid Region.
      Ninety patients were included with diagnoses of subacute or chronic MND without
      neurological damage, 47 patients received MT and 43 TENS. The primary outcome was
      pain intensity measured in millimeters using the Visual Analogue Scale (VAS).
      Also disability, quality of life, adverse effects and sociodemographic and
      prognosis variables were measured. Three evaluations were performed (before, when
      the procedure finished and six months after). Seventy-one patients (79%)
      completed the follow-up measurement at six months. In more than half of the
      treated patients the procedure had a clinically relevant "short term" result
      after having ended the intervention, when either MT or TENS was used. The success
      rate decreased to one-third of the patients 6 months after the intervention. No
      differences can be found in the reduction of pain, in the decrease of disability
      nor in the quality of life between both therapies. Both analyzed physiotherapy
      techniques produce a short-term pain reduction that is clinically relevant.

PMID- 20691632
TI  - Spectral analysis and comparison of mineral deposits forming in opacified
      intraocular lens and senile cataractous lens.
AB  - This preliminary report was attempted to compare the chemical components of
      mineral deposits on the surfaces of an opacified intraocular lens (IOL) and a
      calcified senile cataractous lens (SCL) by vibrational spectral diagnosis. An
      opacified intraocular lens (IOL) was obtained from a 65-year-old male patient who
      had a significant decrease in visual acuity 2-years after an ocular IOL
      implantation. Another SCL with grayish white calcified plaque on the subcapsular
      cortex was isolated from a 79-year-old male patient with complicated cataract
      after cataract surgery. Optical light microscope was used to observe both samples
      and gross pictures were taken. Fourier transform infrared (FT-IR) and Raman
      microspectroscopic techniques were employed to analyze the calcified deposits.
      The curve-fitting algorithm using the Gaussian function was also used to
      quantitatively estimate the chemical components in each deposit. The preliminary
      results of spectral diagnosis indicate that the opacified IOL mainly consisted of
      the poorly crystalline, immature non-stoichiometric hydroxyapatite (HA) with
      higher content of type B carbonated apatites. However, the calcified plaque
      deposited on the SCL was comprised of a mature crystalline stoichiometric HA
      having higher contents of type A and type B carbonate apatites. More case studies
      should be examined in future.

PMID- 20691633
TI  - Effect of Lactobacillus reuteri GMNL-263 treatment on renal fibrosis in diabetic
      rats.
AB  - Hyperglycemia is the most important factor in the progression of renal fibrosis
      in diabetic kidney. Prevention and treatment of renal fibrosis may improve
      diabetic nephropathy. To explore whether probiotic Lactobacillus reuteri GMNL-263
      treatment was linked to altered hyperglycemia-mediated renal fibrosis in diabetic
      kidney, the mechanisms of L. reuteri GMNL-263 treatment responsible for the
      inhibition of renal fibrosis in streptozotocin (STZ)-induced diabetic rats were
      examined. Diabetic rats were induced by intraperitoneal injection of STZ (50
      mg/kg). Induction of diabetes was confirmed by measurement of the blood glucose
      using the glucose oxidase method, and hyperglycemic rats with levels >16 mmol/L
      were used. We found that L. reuteri GMNL-263 treatment caused reduction of
      glycated hemoglobin and blood glucose levels in STZ-induced diabetic rats for 28
      days (all p<0.05). Treatment with L. reuteri GMNL-263 increased body weight but
      decreased kidney weight in diabetic rats as compared to diabetic control
      (p<0.05). In diabetic renal cortex, the Janus kinase 2/signal transducers and
      activators of transcription 1 (but not extracellular signal-regulated kinase/c
      Jun N-terminal kinase/p38 mitogen-activated protein kinase) activation was
      markedly blocked by L. reuteri GMNL-263 treatment. The ability of L. reuteri GMNL
      263 treatment to inhibit renal fibrosis was verified by the observation that it
      significantly decreased protein levels of plasminogen activator inhibitor-1,
      p21(Waf1/Cip1), alpha-smooth muscle actin, and fibronectin in diabetic renal
      cortex. The results obtained in this study indicate that L. reuteri GMNL-263
      treatment may protect STZ-induced diabetic rats from hyperglycemia-enhanced renal
      fibrosis.

PMID- 20691634
TI  - IL-17 and IL-22: siblings, not twins.
AB  - T helper (Th) cell subsets secrete cytokines that regulate other immune cells.
      Interleukin (IL)-17 and IL-22 belong to a new class of cytokines with predominant
      effects on epithelial cells. Thus, these cytokines are key molecules in several
      disease processes. IL-17 and IL-22 are released by leukocytes such as Th and
      natural killer cell populations. Both IL-17 and IL-22 induce an innate immune
      response in epithelial cells, but their functional spectra are generally
      distinct. IL-17 induces an inflammatory tissue response and is involved in the
      pathogenesis of several autoimmune diseases, whereas IL-22 is
      protective/regenerative. This review juxtaposes IL-17 and IL-22 and describes
      overlaps and differences regarding their cellular sources, biochemical structure,
      signaling cascades in target cells, and function.

PMID- 20691636
TI  - What is in a name? Nursing education and human rights legislation.

PMID- 20691635
TI  - B cells and autoantibodies: complex roles in CNS injury.
AB  - Emerging data indicate that traumatic injury to the brain or spinal cord
      activates B lymphocytes, culminating in the production of antibodies specific for
      antigens found within and outside the central nervous system (CNS). Here, we
      summarize what is known about the effects of CNS injury on B cells. We outline
      the potential mechanisms for CNS trauma-induced B cell activation and discuss the
      potential consequences of these injury-induced B cell responses. On the basis of
      recent data, we hypothesize that a subset of autoimmune B cell responses
      initiated by CNS injury are pathogenic and that targeted inhibition of B cells
      could improve recovery in cases of brain and spinal cord injury.

PMID- 20691637
TI  - Time-lapse analysis of mouse embryo development in oxygen gradients.
AB  - Atmospheric oxygen (approximately 20%) in culture significantly impairs
      preimplantation embryo development. However, it is not known whether all stages
      of preimplantation embryo development are susceptible to oxygen toxicity. This
      study investigated the temporal responses of preimplantation embryos to oxygen
      conditions in vitro. Mouse embryos were cultured in atmospheric (approximately
      20%) or lower (5%) oxygen concentrations for the first 48 h, followed by culture
      in the same or reciprocal oxygen concentrations for another 48 h: group 1
      (control, 5 and 5%); group 2 (5 and 20%); group 3 (20 and 5%); and group 4 (20
      and 20%). Time-lapse microscopy was performed with imaging of individual embryos
      at 15-min intervals. Compared with embryos cultured in 5% oxygen, embryos
      cultured in 20% oxygen were delayed at the 1st cleavage by 0.45 h (P<0.05), at
      the 2nd cleavage by 0.84 h (P<0.01) and at the 3rd cleavage by 3.19 h (P<0.001).
      Switching from 20% to 5% oxygen after 48 h did not completely alleviate earlier
      induced perturbations. Partial or complete culture in atmospheric oxygen resulted
      in significantly fewer blastocyst cell numbers compared with control (P<0.05).
      Oxygen can influence mouse embryo development at both the cleavage and post
      compaction stages.

PMID- 20691638
TI  - Re: Review article titled, "Rifamycins - Obstacles and opportunities" by Paul A.
      Aristoff, George A. Garcia, Paul D. Kirchhoff, H.D. Hollis Showalter.
      Tuberculosis 2010; 90(2):94-118.

PMID- 20691639
TI  - The challenges of diagnosing thrombotic thrombocytopenic purpura in the
      critically ill. A case report.
AB  - Thrombotic thrombocytopenic purpura (TTP) is associated with high mortality
      rates. TTP may have various and different presentations depending on the organs
      involved. It is now recognized to be the consequence of reduction of blood levels
      of the disintegrin and metalloprotease with thrombospondin motifs (ADAMTS)-13.
      Prompt diagnosis of TTP is paramount, because plasma exchange is the only
      treatment capable of improving patient's survival with a dual mechanism: removal
      of anti-ADAMTS-13 auto-antibodies and infusion of the active protease available
      in the fresh frozen plasma. We report herein on the challenges in diagnosing TTP
      like complications of post-surgical facial surgery in a young male patient.

PMID- 20691640
TI  - Renewed hope for treatment of spinal and bulbar muscular atrophy?

PMID- 20691642
TI  - Outlook: the postictal state--future directions for research.
AB  - Future directions for research need to include studies of the various
      experimental and clinical aspects of the postictal state. More specifically, we
      need reliable and validated instruments that are able to measure the beginning
      and the end of the postictal period. Although a number of questionnaires are
      available, we currently have no evidence that these tests are able to assess drug
      effects on the postictal state, if they exist. In addition to the need for
      sensitive, reproducible and objective measures of the postictal state, we need
      instruments to differentiate the specific effects of AEDs or non-pharmacological
      therapy on the postictal state from indirect effects because of overall reduction
      in seizure severity. Although it would be naive to think that the mechanisms of
      seizure termination are necessarily less complex than those involved in ictal
      onset, it is certainly worthwhile to explore strategies for the development of a
      new class of drugs for seizure control that work primarily through mechanisms
      involved in seizure termination and postictal refractoriness.

PMID- 20691643
TI  - Quadrant dosimetry as a predictor of biochemical relapse in 125I prostate
      brachytherapy.
AB  - PURPOSE: To evaluate region-specific dose metrics as predictors of biochemical
      relapse in prostate brachytherapy patients. METHODS AND MATERIALS: In a cohort of
      1006 low-risk and "low-tier" intermediate-risk prostate brachytherapy patients
      treated to a planned dose of 144 Gy mPD (minimal peripheral dose), 30 of 32 with
      biochemical relapse (nadir+2 ng/mL definition) had postimplant CT scans available
      for retrospective analysis. These were matched to nonrelapsing controls from the
      same era. Three copies of each CT were created and, after randomization and
      deletion of identifiers and original contours, were re-contoured by three
      radiation oncologists. Prostate contours were then divided into quadrants:
      Anterior-Superior (ASQ), Posterior-Superior (PSQ), Anterior-Inferior (AIQ), and
      Posterior-Inferior (PIQ), and dosimetric parameters calculated. Results were
      analyzed using mixed-effects linear regression and multivariate logistic
      regression. RESULTS: Whole prostate volume of the prostate receiving at least
      100% of the prescribed dose (V(100)) and minimum dose, as a percentage of the
      prescribed dose, received by 90% of the prostate volume (D(90)) were similar for
      relapses and controls (p=0.40 and 0.48, respectively). Among the quadrants, the
      largest differences between relapses and controls were seen for the AIQ. Mean AIQ
      V(100)s were 91.2% (relapses) and 95.5% (controls) (p=0.096), and D(90)s were
      112.8% (relapses) and 119.3% (controls) (p=0.145). Overall, the lowest doses were
      in the ASQ, but were not very different for relapses and controls (V(100)=76.5%
      and 78.5%, respectively) (p=0.54). On multivariate analysis along with various
      clinical parameters, AIQ metrics approached significance at the p <= 0.05 level
      in models that also included initial prostate-specific antigen, androgen
      suppression, and risk group. CONCLUSIONS: Although whole prostate dose metrics
      did not predict for biochemical relapse in our data set, dose to the AIQ was
      predictive in multivariate analysis.

PMID- 20691641
TI  - Efficacy and safety of leuprorelin in patients with spinal and bulbar muscular
      atrophy (JASMITT study): a multicentre, randomised, double-blind, placebo
      controlled trial.
AB  - BACKGROUND: Spinal and bulbar muscular atrophy is a hereditary motor neuron
      disease caused by the expansion of a polyglutamine tract in the androgen
      receptor. At present there are no treatments for spinal and bulbar muscular
      atrophy, although leuprorelin suppressed the accumulation of pathogenic androgen
      receptors in a phase 2 trial. We aimed to assess the efficacy and safety of
      leuprorelin for spinal and bulbar muscular atrophy. METHODS: The Japan SBMA
      Interventional Trial for TAP-144-SR (JASMITT) was a 48-week, randomised, double
      blind, placebo-controlled trial done at 14 hospitals between August, 2006, and
      March, 2008. Patients with spinal and bulbar muscular atrophy were randomly
      assigned (1:1) by minimisation to subcutaneous 11.25 mg leuprorelin or identical
      placebo every 12 weeks. Patients and investigators were masked to treatment
      allocation. The primary endpoint was pharyngeal barium residue, which indicates
      incomplete bolus clearance, measured at week 48 by videofluorography. All
      patients who were randomly assigned and who were assessed with videofluorography
      at least once were included in the analyses. This study is registered with the
      JMACCT clinical trials registry, number JMA-IIA00009, and the UMIN clinical
      trials registry, number UMIN000000465. FINDINGS: 204 patients were randomly
      assigned and 199 started treatment: 100 with leuprorelin and 99 with placebo. At
      week 48, the pharyngeal barium residue after initial swallowing had changed by 
      5.1% (SD 21.0) in the leuprorelin group and by 0.2% (18.2) in the placebo group
      (difference between groups -5.3%; 95% CI -10.8 to 0.3; p=0.063). The mean
      difference in pharyngeal barium residue after piecemeal deglutition at week 48
      was -3.2% (-6.4 to 0.0; p=0.049), but there was no significant difference between
      the groups after covariate adjustment for the baseline data (-4.1 to 1.6;
      p=0.392). In a predefined subgroup analysis, leuprorelin treatment was associated
      with a greater reduction in barium residue after initial swallowing than was
      placebo in patients with a disease duration less than 10 years (difference
      between groups -9.8, -17.1 to -2.5; p=0.009). There were no significant
      differences in the number of drug-related adverse events between groups (57 of
      100 in the leuprorelin group and 54 of 99 in the placebo group; p=0.727).
      INTERPRETATION: 48 weeks of treatment with leuprorelin did not show significant
      effects on swallowing function in patients with spinal and bulbar muscular
      atrophy, although it was well tolerated. Disease duration might influence the
      efficacy of leuprorelin and thus further clinical trials with sensitive outcome
      measures should be done in subpopulations of patients. FUNDING: Large Scale
      Clinical Trial Network Project, Japan and Takeda Pharmaceuticals.

PMID- 20691644
TI  - Minimizing the number of implantation needles for prostate (125)I brachytherapy:
      an investigation of possibilities and implications.
AB  - PURPOSE: Reduction of the number of implantation needles for prostate
      brachytherapy will shorten the duration of implantation procedures and possibly
      reduce trauma-related morbidity. The purpose of this study was to investigate
      possibilities for the minimization of the number of needles and to investigate
      the consequences for the dose distribution. METHODS AND MATERIALS: A planning
      study for six different prostate volumes was performed. The number of needles was
      minimized by changing fixed 1cm interseed spacing to free interseed spacing
      within the needles and by increasing the seed activity. Dose-volume parameters of
      prostate and organs at risk (OAR) bladder, rectum, and urethra were determined.
      For plans with different needle and seed configurations, the sensitivity for
      random seed placement inaccuracies was tested. Dose distributions of realized
      implants based on fixed (n=21) and free interseed spacing (n=21) were compared.
      RESULTS: The average number of needles (+/-1 standard deviation) could be reduced
      from 18.8+/-3.6 to 12.7+/-2.9 (-33%) when changing from fixed interseed spacing
      to free interseed spacing and subsequently to 7.3+/-1.0 (-42%) by increasing the
      seed strength from 0.57U to 1.14U. These needle reductions resulted in increased
      dose inhomogeneity within the prostate and increased sensitivity of dose-volume
      parameters of the OAR for random geometrical inaccuracies. Introduction of free
      interseed spacing in our clinic resulted in very satisfactory dose coverage of
      the prostate (D(90)=172+/-17Gy), while the average number of needles was reduced
      by 30%. CONCLUSIONS: Substantial reduction of the number of implantation needles
      is possible without compromising adequate dose coverage of the prostate. However,
      the chance of an unpredicted high dose to the OAR increases as fewer needles are
      used.

PMID- 20691645
TI  - Web-based application to project the burden of Alzheimer's disease.
AB  - BACKGROUND: Health care planning and research would benefit from tools that
      enable researchers to project the future burden of Alzheimer's disease (AD) and
      evaluate the effect of potential interventions. METHODS: We created a web-based
      application of the AD prevalence model developed by Brookmeyer et al (Am J Public
      Health 1998;88:1337-42; Alzheimers Dement 2007;3:186-91). The user defines the
      disease parameters and any interventions that may either reduce risk or slow
      disease progression. We expanded the parameters to include the cost and weights
      for disability-adjusted life years. APPLICATION: The secure, web-based
      application generates detailed AD projections for each calendar year to 2050, and
      allows users to create personal accounts for them to save, retrieve, and modify
      the input parameters. The flexibility of the application is illustrated with a
      forecast for the state of Maryland, USA. CONCLUSIONS: The application generates
      AD burden projections, costs, and disability-adjusted life years, along with
      changes associated with potential interventions.

PMID- 20691646
TI  - The Werner's Syndrome protein collaborates with REV1 to promote replication fork
      progression on damaged DNA.
AB  - DNA damage tolerance pathways facilitate the bypass of DNA lesions encountered
      during replication. These pathways can be mechanistically divided into
      recombinational damage avoidance and translesion synthesis, in which the lesion
      is directly bypassed by specialised DNA polymerases. We have recently shown
      distinct genetic dependencies for lesion bypass at and behind the replication
      fork in the avian cell line DT40, bypass at the fork requiring REV1 and bypass at
      post-replicative gaps requiring PCNA ubiquitination by RAD18. The WRN
      helicase/exonuclease, which is mutated in the progeroid and cancer predisposition
      disorder Werner's Syndrome, has previously been implicated in a RAD18-dependent
      DNA damage tolerance pathway. However, WRN has also been shown to be required to
      maintain normal replication fork progression on a damaged DNA template, a defect
      reminiscent of REV1-deficient cells. Here we use the avian cell line DT40 to
      demonstrate that WRN assists REV1-dependent translesion synthesis at the
      replication fork and that PCNA ubiquitination-dependent post-replicative lesion
      bypass provides an important backup mechanism for damage tolerance in the absence
      of WRN protein.

PMID- 20691647
TI  - [Evaluation of weight, height and BMI in children, adolescents and young adults
      from the Community of Madrid].
AB  - INTRODUCTION: The data of four growth studies involving populations from
      Andalusia, Barcelona, Bilbao and Zaragoza have recently been reported as part of
      the Spanish Cross-sectional Growth Study 2008 (SCGS). With the aim of detecting
      possible differences between the population of the Madrid region and those of the
      SCGS, and by so-doing assess the applicability of the conclusions of this
      reference work to the Madrid region, a cross-sectional study of the latter was
      undertaken, recording the weight, height and body mass index (BMI). SUBJECTS AND
      METHODS: We have analyzed 6463 subjects (3055 females and 3408 males) aged 3-24
      years. All subjects were healthy, Caucasian, and of Spanish origin. Differences
      between the results of the Madrid and SCGS studies were sought by multiple linear
      regression analysis of the log of the height, weight and BMI data adjusted for
      age and geographical area. The Tukey multiple comparisons test was used to
      analyse differences in age ranges. All calculations were performed using SAS v.
      8.2 software. RESULTS: Means and standard deviations are provided for the weight,
      height and BMI of women and men; distributions by percentiles are also provided.
      No differences of clinical importance were seen in the weight, height or BMI
      between the subjects of the Madrid region and those of the SCGS. However,
      comparisons with the results of other studies performed more than 20 years ago
      revealed an increase in the weight and height values in all percentiles.
      CONCLUSIONS: In summary, the official Spanish SCGS reference data for 2008 are
      similar to those recorded for the Madrid region. Bearing in mind that recent
      cross-sectional studies undertaken in Andalusia, Aragon, Catalonia, the Basque
      Country and the present work show no significant differences in mean weights,
      heights or BMIs in any age group, nor in the final height attained by adults, the
      Spanish population would appear to be anthropometrically homogeneous. The
      conclusions of the SCGS may therefore be applicable to the entire country.

PMID- 20691648
TI  - [Signs of punctiform haemorrhage on the pillow].

PMID- 20691649
TI  - Lyophilized somatic cells direct embryonic development after whole cell
      intracytoplasmic injection into pig oocytes.
AB  - The study investigated the feasibility of lyophilization for long-term
      preservation of somatic cells and embryonic development after whole cell
      intracytoplasmic injection (WCICI) into enucleated pig oocyte. Confluent cultured
      porcine fetal fibroblast (pFF) cells were lyophilized and stored at 4 degrees C
      for at least 6 months. Results showed that compared to non-lyophilized control
      cells, lyophilized cells had drastically reduced cellular viability (P<0.01).
      WCICI of reconstituted lyophilized cells could support complete embryonic
      development. However, the rates of cleavage (64.7+/-2.7 vs. 43.5+/-4.7%) and
      blastocyst formation (18.2+/-0.6 vs. 10.2+/-1.6%) were lower than that of control
      (P<0.05). Total nuclei number per blastocyst (30.4+/-4.5 vs. 25.2+/-4.7) and
      intensity of acetylation at histone H3 (AcH3) protein (55.9+/-3.5 vs. 53.3+/-3.8)
      did not differ (P>0.05). The development ability of embryos, produced from
      lyophilized somatic cells, was further increased (19.5+/-2.4 vs. 10.2+/-1.6%;
      P<0.05) by treatment with trichostatin A (TSA) for 24h post-activation. These TSA
      treated embryos also had AcH3 level comparable with in vitro fertilized embryos
      (63.1+/-3.2 vs. 69.9+/-1.3). In conclusion, our results suggest that lyophilized
      somatic cells can direct embryonic development up to blastocyst stage after WCICI
      into pig oocytes. Treatment of embryos, produced from lyophilized somatic cells,
      with TSA can further increase their in vitro developmental potential.

PMID- 20691650
TI  - Acute stress rapidly decreases plasma testosterone in a free-ranging male
      songbird: potential site of action and mechanism.
AB  - We used a free-ranging, seasonally breeding adult male songbird, the rufous
      winged sparrow, Aimophila carpalis, to investigate the effects of acute stress
      induced by capture followed by restraint, on the hypothalamo-pituitary-testicular
      axis. Intra- and interindividual comparisons revealed that males decreased their
      plasma testosterone (T) by 37-52% in response to acute stress. The decrease
      occurred within 15 min of capture and persisted for at least another 15 min.
      Within 15 min, the decrease in plasma T was not associated with a reduction in
      plasma luteinizing hormone (LH). Thirty minutes after capture and restraint, the
      decrease in plasma T either was likewise not associated with decreased plasma LH
      (intraindividual comparison) or concurred with a reduction in plasma LH
      (interindividual comparison). These observations indicate that effects of stress
      may have been mediated at the pituitary gland and also directly at the testicular
      levels. To address this question, we measured the hormonal response to an
      injection of the glutamate receptor agonist N-methyl-d,l-aspartate (NMA) to
      stimulate to stimulate the release of gonadotropin-releasing hormone (GnRH) or of
      GnRH to stimulate the release of LH. Treatment with NMA did not change plasma LH,
      presumably because the birds were in breeding condition and already secreting
      GnRH at a maximum rate. Administration of GnRH increased plasma LH equally in
      birds that were or were not stressed before the treatment. An injection of
      purified ovine LH (oLH) increased plasma T equally in birds that were or were not
      acutely stressed before the hormone injection. Thus, the observed acute stress
      induced decrease in plasma T was apparently not mediated by decreased
      responsiveness of the pituitary gland to GnRH or of the testes to LH. Decreased
      plasma T following stress may involve a direct impairment of the testicular
      endocrine function.

PMID- 20691651
TI  - Molecular cloning of a putative crustacean hyperglycemic hormone (CHH) isoform
      from extra-eyestalk tissue of the blue crab (Callinectes sapidus), and
      determination of temporal and spatial patterns of CHH gene expression.
AB  - Crustacean hyperglycemic hormone (CHH) is a polypeptide neurohormone involved in
      regulation of multiple physiological processes. We report here the cloning from
      thoracic ganglia of the blue crab (Callinectes sapidus) a cDNA (CsCHH-2) encoding
      a putative CHH isoform (CsCHH-2). CsCHH-2 is structurally similar to a putative
      preproCHH (CsCHH-1) previously cloned from eyestalk ganglia of C. sapidus. The
      two preprohormones possess an identical signal peptide and CHH precursor related
      peptide, but differ in the mature CHH polypeptide. An analysis by RT-PCR of the
      tissue distribution of CsCHH-1 and CsCHH-2 revealed the former is restricted to
      eyestalk neural ganglia, while the latter is widely distributed among tissues.
      The type of CHH transcript present in eyestalk and thoracic ganglia did not vary
      as a function of the molt cycle. An assessment of transcript abundance in tissues
      of intermolt crabs showed the abundance of the CsCHH-1 transcript in eyestalk
      ganglia far exceeds the abundance of the CsCHH-2 transcript in extra-eyestalk
      tissue. An assessment of transcript abundance during a molt cycle showed CsCHH-1
      transcript abundance in eyestalk ganglia was low during intermolt, rose during
      premolt, reaching a peak in D(3), then fell prior to molting, and remained low
      during postmolt. By contrast, CsCHH-2 transcript abundance in thoracic ganglia
      was low during intermolt, rose sharply during D(2), then dropped in D(3) and
      remained low during postmolt. The results are consistent with the hypothesis that
      CsCHH-1 and CsCHH-2 differ with respect to physiological function.

PMID- 20691652
TI  - Molecular characterization, tissue distribution, and mRNA expression profiles of
      two Kiss genes in the adult male and female chub mackerel (Scomber japonicus)
      during different gonadal stages.
AB  - Kisspeptins, encoded by the Kiss1 gene, have emerged as key modulators of
      reproduction in mammals. In contrast to the placental mammals, some teleosts
      express two Kiss genes, Kiss1 and Kiss2. In the present study, full-length cDNAs
      of Kiss1 and Kiss2 in the chub mackerel were cloned and sequenced. Chub mackerel
      Kiss1 and Kiss2 cDNAs encode 105 and 123 amino acids, respectively. A comparison
      of the deduced amino acid sequences of chub mackerel Kiss1 and Kiss2 with those
      of other vertebrate species showed a high degree of conservation only in the
      kisspeptin-10 region (Kp-10). The Kp-10 of chub mackerel Kiss1 (YNFNSFGLRY) and
      Kiss2 (FNFNPFGLRF) showed variations at three amino acids. Tissue distribution
      analysis using quantitative real-time PCR (qRT-PCR) revealed that the Kiss1 and
      Kiss2 transcripts were expressed in different tissues of adult chub mackerel. In
      addition, their levels in the adipose tissue exhibited sexually dimorphic
      expression. Further, to have a basic understanding on the involvement of Kiss1
      and Kiss2 in the seasonal gonadal development, their relative mRNA expression
      profiles in the brain, pituitary, and gonads at different gonadal stages were
      analyzed using qRT-PCR. Kiss1 and Kiss2 levels in the brain showed a differential
      expression profile between male and female fish. In males, Kiss1 and Kiss2 levels
      gradually decreased from the immature stage to spermiation and reached a minimal
      level during the post-spawning period. In contrast, Kiss1 levels in the brain of
      females did not vary significantly among the different gonadal stages. However,
      Kiss2 levels fluctuated as that of males, gradually declining from the immature
      stage to the post-spawning period. The pituitary Kiss1 levels did not show
      significant fluctuations. However, Kiss1 levels in the gonads were highly
      elevated during spermiation and late vitellogenesis compared to the immature and
      post-spawning period. These results suggest the possible involvement of two Kiss
      genes in the brain and Kiss1 in the gonads of chub mackerel during seasonal
      gonadal development.

PMID- 20691654
TI  - Differential activation of host cell signalling pathways through infection with
      two variants of influenza A/Puerto Rico/8/34 (H1N1) in MDCK cells.
AB  - In cell culture-based influenza vaccine production, few efforts have been
      undertaken to characterise virus-host cell interactions in detail. Two influenza
      virus strains that grew to different virus titres, and differed in virus
      dynamics, apoptosis induction and proteome changes were observed. In order to
      elucidate biological mechanisms related to these differences, the induction of
      signalling cascades in adherent MDCK cells infected with two variants of
      influenza A/PuertoRico/8/34 (H1N1) was analysed. The pathways chosen for analysis
      are key components of the innate immune response and crucial for influenza A
      virus replication (NF-kappaB, IRF-3, PI3K-Akt, Jak-Stat, Raf/MEK/ERK,
      PKR/eIF2alpha). Interestingly, all investigated pathways were induced stronger by
      PR8-NIBSC than by PR8-RKI, the virus variant which results in higher virus
      titres. In particular, PR8-NIBSC infection lead to a higher induction of IFN-beta
      as well as IFN-stimulated gene expression, which was confirmed by Western blot as
      well as real-time PCR. Overall, results obtained clearly facilitate
      interpretation of observations regarding proteome changes and virus-induced
      apoptosis in cell culture-based vaccine manufacturing processes and support
      efforts towards design of improved host cell lines.

PMID- 20691653
TI  - Delivery of woodchuck hepatitis virus-like particle presented influenza M2e by
      recombinant attenuated Salmonella displaying a delayed lysis phenotype.
AB  - The use of live recombinant attenuated Salmonella vaccines (RASV) is a promising
      approach for controlling infections by multiple pathogens. The highly conserved
      extracellular domain of the influenza M2 protein (M2e) has been shown to provide
      broad spectrum protection against multiple influenza subtypes sharing similar M2e
      sequences. An M2e epitope common to a number of avian influenza subtypes was
      inserted into the core antigen of woodchuck hepatitis virus and expressed in two
      different recombinant attenuated Salmonella Typhimurium strains. One strain was
      attenuated via deletion of the cya and crp genes. The second strain was
      engineered to exhibit a programmed delayed lysis phenotype. Both strains were
      able to produce both monomeric fusion proteins and fully assembled core
      particles. Mice orally immunized with the strain exhibiting delayed lysis induced
      significantly greater antibody titers than the Deltacya Deltacrp strain and
      provided moderate protection against weight loss to a low level challenge with
      the influenza strain A/WSN/33 modified to express the M2e sequence common to
      avian viruses. Further studies indicated that the Salmonella expressed core
      antigen induced comparable antibody levels to the purified core antigen injected
      with an alum adjuvant and that both are able to reduce viral replication in the
      lungs. To our knowledge this is the first report demonstrating Salmonella
      mediated delivery of influenza virus M2e protein in a mammalian host to induce a
      protective immune response against viral challenge.

PMID- 20691655
TI  - A kinetic assay of mitochondrial ADP-ATP exchange rate in permeabilized cells.
AB  - We previously described a method to measure ADP-ATP exchange rates in isolated
      mitochondria by recording the changes in free extramitochondrial [Mg(2+)]
      reported by an Mg(2+)-sensitive fluorescent indicator, exploiting the
      differential affinity of ADP and ATP to Mg(2+). In the current article, we
      describe a modification of this method suited for following ADP-ATP exchange
      rates in environments with competing reactions that interconvert adenine
      nucleotides such as in permeabilized cells that harbor phosphorylases and
      kinases, ion pumps exhibiting substantial ATPase activity, and myosin ATPase
      activity. Here we report that the addition of BeF(3)(-) and sodium orthovanadate
      (Na(3)VO(4)) to medium containing digitonin-permeabilized cells inhibits all ADP
      ATP-using reactions except the adenine nucleotide translocase (ANT)-mediated
      mitochondrial ADP-ATP exchange. An advantage of this assay is that mitochondria
      that may have been also permeabilized by digitonin do not contribute to ATP
      consumption by the exposed F(1)F(o)-ATPase due to its sensitivity to BeF(3)(-)
      and Na(3)VO(4). With this assay, ADP-ATP exchange rate mediated by the ANT in
      permeabilized cells is measured for the entire range of mitochondrial membrane
      potential titrated by stepwise additions of an uncoupler and expressed as a
      function of citrate synthase activity per total amount of protein.

PMID- 20691656
TI  - Novel fluorescent dyes based on oligopropylamines for the in vivo staining of
      eukaryotic unicellular algae.
AB  - Weakly basic fluorescent dyes are used to visualize organelles within live cells
      due to their affinity to acidic subcellular organelles. In particular, they are
      used to stain the silica deposited in the silica deposition vesicles (SDVs) of
      diatoms during the course of their frustule synthesis. This study involved the
      synthesis of fluorescent dyes derived from oligopropylamines, compounds similar
      to those found in diatoms. The dyes were obtained by reacting oligopropylamines
      with 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole. The reaction was realized using
      methylated oligopropylamines with two or three nitrogen atoms and yielded two
      novel fluorescent dyes: NBD-N2 and NBD-N3. The dyes appeared to be highly
      efficient in the in vivo staining of growing siliceous frustules of diatoms at
      concentrations at least 10 times lower than those required for staining with HCK
      123. NBD-N3 also efficiently stained other subcellular vesicles of eukaryotic
      unicellular algae. NBD-N2 stained only growing diatom frustules, whereas NBD-N3
      also stained various subcellular organelles of different eukaryotic unicellular
      algae. NBD-N2 and NBD-N3 were not removed from stained diatom frustules by
      drastic treatments with H(2)SO(4) and H(2)O(2). Fluorescent silica can also be
      obtained by its chemical precipitation in the presence of NBD-N2 and NBD-N3.

PMID- 20691657
TI  - Distribution of radiolabeled l-glutamate and d-aspartate from blood into
      peripheral tissues in naive rats: significance for brain neuroprotection.
AB  - Excess l-glutamate (glutamate) levels in brain interstitial and cerebrospinal
      fluids (ISF and CSF, respectively) are the hallmark of several neurodegenerative
      conditions such as stroke, traumatic brain injury or amyotrophic lateral
      sclerosis. Its removal could prevent the glutamate excitotoxicity that causes
      long-lasting neurological deficits. As in previous studies, we have established
      the role of blood glutamate levels in brain neuroprotection, we have now
      investigated the contribution of the peripheral organs to the homeostasis of
      glutamate in blood. We have administered naive rats with intravenous injections
      of either l-[1-(14)C] Glutamic acid (l-[1-(14)C] Glu), l-[G-(3)H] Glutamic acid
      (l-[G-(3)H] Glu) or d-[2,3-(3)H] Aspartic acid (d-[2,3-(3)H] Asp), a non
      metabolized analog of glutamate, and have followed their distribution into
      peripheral organs. We have observed that the decay of the radioactivity
      associated with l-[1-(14)C] Glu and l-[G-(3)H] Glu was faster than that
      associated with glutamate non-metabolized analog, d-[2,3-(3)H] Asp. l-[1-(14)C]
      Glu was subjected in blood to a rapid decarboxylation with the loss of (14)CO(2).
      The three major sequestrating organs, serving as depots for the eliminated
      glutamate and/or its metabolites were skeletal muscle, liver and gut,
      contributing together 92% or 87% of total l-[U-(14)C] Glu or d-[2,3-(3)H] Asp
      radioactivity capture. l-[U-(14)C] Glu and d-[2,3-(3)H] Asp showed a different
      organ sequestration pattern. We conclude that glutamate is rapidly eliminated
      from the blood into peripheral tissues, mainly in non-metabolized form. The liver
      plays a central role in glutamate metabolism and serves as an origin for
      glutamate metabolites that redistribute into skeletal muscle and gut. The
      findings of this study suggest now that pharmacological manipulations that reduce
      the liver glutamate release rate or cause a boosting of the skeletal muscle
      glutamate pumping rate are likely to cause brain neuroprotection.

PMID- 20691658
TI  - Induction of cereblon by NF-E2-related factor 2 in neuroblastoma cells exposed to
      hypoxia-reoxygenation.
AB  - Cereblon is a protein encoded by the CRBN gene, which has been associated with
      human autosomal recessive nonsyndromic mental retardation. However, little is
      known about the regulation of CRBN expression. Following exposure of mouse
      neuroblastoma N2A cells to hypoxia/reoxygenation (H/R), mRNA and protein
      expression of CRBN were increased. To better understand how CRBN expression is
      regulated, the promoter region of the mouse CRBN gene was characterized
      functionally. Deletion mutations and site-directed mutagenesis led to the
      identification of a functional NF-E2-related factor 2 (Nrf2)-binding site.
      Electrophoretic mobility shift analysis indicated that Nrf2 binds to a putative
      binding site in the CRBN promoter. Nrf2 overexpression and tert-butylhydroquinone
      treatment enhanced CRBN protein expression. These results imply that Nrf2
      stimulates CRBN gene transcription under H/R conditions in neuronal cells.

PMID- 20691659
TI  - EWS-FLI1 inhibits TNFalpha-induced NFkappaB-dependent transcription in Ewing
      sarcoma cells.
AB  - Ewing sarcoma is primarily caused by a t(11;22) chromosomal translocation
      encoding the EWS-FLI1 fusion protein. To exert its oncogenic function, EWS-FLI1
      acts as an aberrant transcription factor, broadly altering the gene expression
      profile of tumor cells. Nuclear factor-kappaB (NFkappaB) is a tightly regulated
      transcription factor controlling cell survival, proliferation and
      differentiation, as well as tumorigenesis. NFkappaB activity is very low in
      unstimulated Ewing sarcoma cells, but can be induced in response to tumor
      necrosis factor (TNF). We wondered whether NFkappaB activity could be modulated
      by EWS-FLI1 in Ewing sarcoma. Using a knockdown approach in Ewing sarcoma cells,
      we demonstrated that EWS-FLI1 has no influence on NFkappaB basal activity, but
      impairs TNF-induced NFkappaB-driven transcription, at least in part through
      inhibition of NFkappaB binding to DNA. We detected an in vivo physical
      interaction between the fusion protein and NFkappaB p65, which could mediate
      these effects. Our findings suggest that, besides directly controlling the
      activity of its primary target promoters, EWS-FLI1 can also indirectly influence
      gene expression in tumor cells by modulating the activity of key transcription
      factors such as NFkappaB.

PMID- 20691660
TI  - A novel nucleic acid analogue shows strong angiogenic activity.
AB  - A novel nucleic acid analogue (2Cl-C.OXT-A) significantly stimulated tube
      formation of human umbilical endothelial cells (HUVEC). Its maximum potency at
      100muM was stronger than that of vascular endothelial growth factor (VEGF), a
      positive control. At this concentration, 2Cl-C.OXT-A moderately stimulated
      proliferation as well as migration of HUVEC. To gain mechanistic insights how 2Cl
      C.OXT-A promotes angiogenic responses in HUVEC, we performed immunoblot analyses
      using phospho-specific antibodies as probes. 2Cl-C.OXT-A induced robust
      phosphorylation/activation of MAP kinase ERK1/2 and an upstream MAP kinase kinase
      MEK. Conversely, a MEK inhibitor PD98059 abolished ERK1/2 activation and tube
      formation both enhanced by 2Cl-C.OXT-A. In contrast, MAP kinase responses
      elicited by 2Cl-C.OXT-A were not inhibited by SU5416, a specific inhibitor of
      VEGF receptor tyrosine kinase. Collectively these results suggest that 2Cl-C.OXT
      A-induces angiogenic responses in HUVEC mediated by a MAP kinase cascade
      comprising MEK and ERK1/2, but independently of VEGF receptor tyrosine kinase. In
      vivo assay using chicken chorioallantoic membrane (CAM) and rabbit cornea also
      suggested the angiogenic potency of 2Cl-C.OXT-A.

PMID- 20691661
TI  - Molecular characterization of TGFbeta-induced epithelial-mesenchymal transition
      in normal finite lifespan human mammary epithelial cells.
AB  - Epithelial-mesenchymal transition (EMT) is a morphogenetic program essential for
      embryonic development and wound healing, but can adversely cause fibrosis and
      metastatic cancer progression when deregulated. Here, we established a model of
      efficient EMT induction in normal finite lifespan human mammary epithelial cells
      (HMEC) using transforming growth factor beta (TGFbeta). We demonstrate that EMT
      in HMEC occurs in three distinctive phases that are governed by a hierarchy of
      EMT-activating transcription factors (TFs). Loss of epithelial cell polarity (ZO
      1), and acquisition of mesenchymal marker (Vimentin, Fibronectin) expression are
      immediate-early events, whereas switching from E-cadherin to N-cadherin protein
      expression occurs only after EMT-like morphological changes become apparent. The
      kinetics of TF induction suggests that ZEB1 and SNAIL mediate early EMT induction
      reinforced by ZEB2, while GOOSECOID and FOXC2 may play a role in EMT maintenance.
      TWIST and SLUG were not significantly induced in this system. Furthermore, we
      show for the first time that normal HMEC acquire a CD44(+)/CD24(-/low) stem cell
      phenotype during a third phase of EMT that is characterized by maximum TF
      expression levels. Our results may have important implications for understanding
      potential changes that might occur in normal breast epithelium under pathological
      conditions triggering elevated TGFbeta levels.

PMID- 20691662
TI  - TCR-induced Akt serine 473 phosphorylation is regulated by protein kinase C
      alpha.
AB  - Akt signaling plays a central role in T cell functions, such as proliferation,
      apoptosis, and regulatory T cell development. Phosphorylation at Ser(473) in the
      hydrophobic motif, along with Thr(308) in its activation loop, is considered
      necessary for Akt function. It is widely accepted that phosphoinositide-dependent
      kinase 1 (PDK-1) phosphorylates Akt at Thr(308), but the kinase(s) responsible
      for phosphorylating Akt at Ser(473) (PDK-2) remains elusive. The existence of PDK
      2 is considered to be specific to cell type and stimulus. PDK-2 in T cells in
      response to TCR stimulation has not been clearly defined. In this study, we found
      that conventional PKC positively regulated TCR-induced Akt Ser(473)
      phosphorylation. PKC-alpha purified from T cells can phosphorylate Akt at
      Ser(473) in vitro upon TCR stimulation. Knockdown of PKC-alpha in T-cell-line
      Jurkat cells reduced TCR-induced phosphorylation of Akt as well as its downstream
      targets. Thus our results suggest that PKC-alpha is a candidate for PDK-2 in T
      cells upon TCR stimulation.

PMID- 20691663
TI  - Flavohemoglobin and nitric oxide detoxification in the human protozoan parasite
      Giardia intestinalis.
AB  - Flavohemoglobins (flavoHbs), commonly found in bacteria and fungi, afford
      protection from nitrosative stress by degrading nitric oxide (NO) to nitrate.
      Giardia intestinalis, a microaerophilic parasite causing one of the most common
      intestinal human infectious diseases worldwide, is the only pathogenic protozoon
      as yet identified coding for a flavoHb. By NO amperometry we show that, in the
      presence of NADH, the recombinant Giardia flavoHb metabolizes NO with high
      efficacy under aerobic conditions (TN=116+/-10s(-1) at 1microM NO, T=37 degrees
      C). The activity is [O(2)]-dependent and characterized by an apparent
      K(M,O2)=22+/-7microM. Immunoblotting analysis shows that the protein is expressed
      at low levels in the vegetative trophozoites of Giardia; accordingly, these cells
      aerobically metabolize NO with low efficacy. Interestingly, in response to
      nitrosative stress (24-h incubation with 5mM nitrite) flavoHb expression is
      enhanced and the trophozoites thereby become able to metabolize NO efficiently,
      the activity being sensitive to both cyanide and carbon monoxide. The NO-donors S
      nitrosoglutathione (GSNO) and DETA-NONOate mimicked the effect of nitrite on
      flavoHb expression. We propose that physiologically flavoHb contributes to NO
      detoxification in G. intestinalis.

PMID- 20691664
TI  - Foxn3 is essential for craniofacial development in mice and a putative candidate
      involved in human congenital craniofacial defects.
AB  - The fork-head transcription factors are involved in a variety of physiological
      processes including development, aging, obesity, and cancer. The fork-head
      transcription factor FOXN3 has been implicated in cell cycle and transcription
      regulation at the cellular level. However, the physiological functions of FOXN3
      in mammals are not known. To understand the role of the fork-head transcription
      factor FOXN3 in mammalian development, we have generated a mutant mouse model for
      the Foxn3 gene. Our analysis shows that the Foxn3 mutation leads to partial
      embryonic and postnatal lethality, growth retardation, eye formation defects,
      dental anomalies and craniofacial defects. Foxn3 mutant tissues and cells are
      also defective in the expression of distinct osteogenic genes. Interestingly, the
      phenotypes of Foxn3 mutant mice show a striking overlap with the clinical
      features of human patients with congenital defects and chromosomal aberrations
      involving the human FOXN3 locus. More than three fourths of human congenital
      disorders involve craniofacial malformations and a majority of the perturbed
      genetic components that lead to such disorders are yet to be identified. Our
      results implicate a role for the FOXN3 gene in the etiology of craniofacial
      defects in humans.

PMID- 20691665
TI  - Monocyte chemoattractant protein-1/CC chemokine ligand 2 enhances apoptotic cell
      removal by macrophages through Rac1 activation.
AB  - Apoptotic cell removal (efferocytosis) is an essential process in the regulation
      of inflammation and tissue repair. We have shown that monocyte chemoattractant
      protein-1/CC chemokine ligand 2 (MCP-1/CCL2) enhances efferocytosis by alveolar
      macrophages in murine bacterial pneumonia. However, the mechanism by which MCP-1
      exerts this effect remains to be determined. Here we explored that hypothesis
      that MCP-1 enhances efferocytosis through a Rac1/phosphatidylinositol 3-kinase
      (PI3-kinase)-dependent mechanism. We assessed phagocytosis of apoptotic cells by
      MCP-1 treated murine macrophages in vitro and in vivo. Rac activity in
      macrophages was measured using a Rac pull down assay and an ELISA based assay
      (GLISA). The downstream Rac1 activation pathway was studied using a specific Rac1
      inhibitor and PI3-kinase inhibitor in in vitro assays. MCP-1 enhanced
      efferocytosis of apoptotic cells by murine alveolar macrophages (AMs), peritoneal
      macrophages (PMs), the J774 macrophage cell line (J774s) in vitro, and murine AMs
      in vivo. Rac1 activation was demonstrated in these cell lines. The effect of MCP
      1 on efferocytosis was completely negated by the Rac1 inhibitor and PI3-kinase
      inhibitor. We demonstrated that MCP-1 enhances efferocytosis in a Rac1-PI3 kinase
      dependent manner. Therefore, MCP-1-Rac1-PI3K interaction plays a critical role in
      resolution of acute lung inflammation.

PMID- 20691666
TI  - The NH(2)-terminus of K(+)-Cl(-) cotransporter 3a is essential for up-regulation
      of Na(+),K(+)-ATPase activity.
AB  - K(+)-Cl(-) cotransporter-3 has two major amino terminal variants, KCC3a and
      KCC3b. In LLC-PK1 cells, exogenously expressed KCC3a co-immunoprecipitated with
      endogenous Na(+),K(+)-ATPase alpha1-subunit (alpha1NaK), accompanying significant
      increases of the Na(+),K(+)-ATPase activity. Exogenously expressed KCC3b did not
      co-immunoprecipitate with endogenous alpha1NaK inducing no change of the
      Na(+),K(+)-ATPase activity. A KCC inhibitor attenuated the Na(+),K(+)-ATPase
      activity in rat gastric mucosa in which KCC3a is predominantly expressed, while
      it had no effects on the Na(+),K(+)-ATPase activity in rat kidney in which KCC3b
      is predominantly expressed. In these tissue samples, KCC3a co-immunoprecipitated
      with alpha1NaK, while KCC3b did not. Our results suggest that the NH(2)-terminus
      of KCC3a is a key region for association with alpha1NaK, and that KCC3a but not
      KCC3b can regulate the Na(+),K(+)-ATPase activity.

PMID- 20691667
TI  - Expression and functional role of inhibitor-of-apoptosis protein livin (BIRC7) in
      neuroblastoma.
AB  - We evaluated the expression of the inhibitor-of-apoptosis protein (IAP)livin
      (BIRC7)in 59 cases ofneuroblastoma (NBL) by quantitative RT-PCR. We also examined
      the role of livin in protecting tumor cells from chemotherapy drugs. Livin
      expression varied significantly amongtumors. High levels of expression were
      observed in 17 of 39 patients with advanced stages (stages 3 and 4) and 6 of 20
      patients with localized stages (stages 1 and 2). Livin-transfected, MYCN
      amplified NBL cells showed increased resistance to doxorubicin and etoposide.
      Conversely, livin knockdown with siRNA enhanced spontaneous and drug-induced
      apoptosis in NBL cells. Multivariate analysis of prognostic factors showed that
      high livin expression worsened prognosis for patients with MYCN-amplified tumors.
      Our data suggest that (i) livin is frequently expressed in NBL and protects tumor
      cells with amplified MYCN oncogene from genotoxic agents; (ii) the antiapoptotic
      effect of livin in NBL is blocked by siRNA; (iii) in the sample studied, high
      livin expression enhanced the adverse prognostic impact of MYCN amplification.
      These findings suggest that livin may contribute to drug resistance in NBL.

PMID- 20691668
TI  - Irreversible inhibition of RANK expression as a possible mechanism for IL-3
      inhibition of RANKL-induced osteoclastogenesis.
AB  - IL-3, a cytokine secreted by activated T lymphocytes, stimulates the
      proliferation, differentiation and survival of pluripotent hematopoietic stem
      cells. In this study, we investigated the mechanism of inhibitory action of IL-3
      on osteoclast differentiation. We show here that IL-3 significantly inhibits
      receptor activator of NF-kappaB (RANK) ligand (RANKL)-induced activation of c-Jun
      N-terminal kinase (JNK). IL-3 down-regulates expression of c-Fos and nuclear
      factor of activated T cells (NFATc1) transcription factors. In addition, IL-3
      down-regulates RANK expression posttranscriptionally in both purified osteoclast
      precursors and whole bone marrow cells. Furthermore, the inhibitory effect of IL
      3 on RANK expression was irreversible. Interestingly, IL-3 inhibits in vivo RANK
      expression in mice. Thus, we provide the first evidence that IL-3 irreversibly
      inhibits RANK expression that results in inhibition of important signaling
      molecules induced by RANKL.

PMID- 20691669
TI  - Peri-hemorrhagic degeneration accompanies stereotaxic collagenase-mediated
      cortical hemorrhage in mouse.
AB  - The cortex is a key brain region vulnerable to intracerebral hemorrhage (ICH)
      associated with stroke and head trauma. Animal models of ICH, via blood or
      collagenase infusion, have been developed most commonly to target the striatum.
      Here, we show that stereotaxic injection of collagenase type IV into two sites of
      the right cortex of adult C57BL6 mice produced hemorrhage to the cortex,
      subcortical white matter and hippocampus at day 1 post-injury, followed by
      cortical volume decrement by day 7. Reductions in MAP2- and NeuN-positive neurons
      were detected at day 1 and 7 post-injury in the core and peri-hemorrhagic cortex,
      respectively. Fluoro-Jade positive degenerating neurons were observed at day 1 in
      the peri-hemorrhagic area. An aberrant aggregation of GFAP-positive astrocytes
      and a significant reduction in RIP-positive oligodendroglial cells were detected
      at day 7 post-injury in the cortical area. In addition, a significant decrement
      in retrogradely Cholera Toxin Subunit B-labeled corticospinal neurons was
      recognized at day 14 post-injury in the ipsilateral cortex. Among the behavioral
      tests employed, the pole climb movement test robustly detected significant motor
      dysfunction at day 1, 3, and 7 post-injury that positively but inversely
      correlated with cortical volume at day 1 and 7 post-injury, respectively. The
      consistent observation of neuronal cell loss in the hemorrhagic core that
      subsequently extended to degeneration of neurons in the peri-hemorrhagic area,
      with accompanying motor abnormalities at least up to the subacute phase, advances
      this cortical hemorrhage model as a platform for examining the pathophysiology of
      and experimental treatments for ICH.

PMID- 20691670
TI  - Separating the visual sentence N400 effect from the P400 sequential expectancy
      effect: cognitive and neuroanatomical implications.
AB  - The N400 is an event-related potential (ERP) component that is elicited by
      semantically meaningful stimuli; one of its defining characteristics is that it
      is amplified for sentence completions that are semantically unexpected or
      incongruous with the preceding context. Some prior reports using visual sentence
      reading paradigms have suggested that there may also be a Cz-centered P400 (a
      P400cz) that is also responding to semantic congruity manipulations, distinct
      from the classic Pz-centered N400 (the N400pz). In the present experiment,
      sentences were presented visually one word at a time, and half of the sentences
      ended with a semantically incongruent ending. High-density 129-channel event
      related potential data were recorded from 26 participants. A combination of
      temporo-spatial principal components analysis (PCA) and item averaging was
      applied to decompose the waveforms. The presence of the P400cz was confirmed. The
      P400cz was much more sensitive to congruity and somewhat more sensitive to cloze
      probability than the N400pz. The separation of the N400 semantic effect into
      these two portions is consistent with both MEG studies and intracranial studies.
      The data suggest that the N400pz has its major source in the bilateral anterior
      medial temporal lobe (AMTL) whereas it is suggested that the P400cz has its major
      source in the medial parietal region. It is further suggested that whereas the
      N400pz process appears to be semantic in nature, some prior reports suggest that
      the P400cz reflects a general sequential expectancy system.

PMID- 20691671
TI  - Mismatch between changes in baicalein-induced memory-related biochemical
      parameters and behavioral consequences in mouse.
AB  - Baicalein is one of the major flavonoids originally isolated from the roots of
      Scutellaria baicalensis Georgi (Labiatae). Reports on baicalein-induced changes
      in memory-related biochemical parameters including extracellular signal-regulated
      kinases (ERK), Akt, cAMP response element-binding protein (CREB), and brain
      derived neurotrophic factor (BDNF) have been scarce, and the action of baicalein
      is controversial. Baicalein promotes phosphorylation of ERK under normal
      conditions; on the other hand, it inhibits phosphorylation of ERK extracellularly
      under oxidative conditions. In the present study, we observed that baicalein
      (20mg/kg, p.o.) as compared to vehicle significantly increased the expression of
      phosphorylated ERK (pERK), phosphorylated CREB (pCREB), and BDNF but did not
      increase phosphorylated Akt expression in the hippocampus of naive mice.
      Baicalein also significantly increased the expression of pERK and BDNF in the
      cortex of naive mice. However, baicalein had no effect on memory acquisition in
      the step-through passive avoidance task. On the contrary, baicalein (20mg/kg,
      p.o.) co-injected with flumazenil (10mg/kg, i.p.) significantly increased the
      retention latency in the passive avoidance task in comparison to the flumazenil
      treated group, baicalein-treated group, and vehicle-treated control group. In
      addition, the number of platform crossings in the Morris water maze test during
      the probe trial session was significantly increased by co-administration of
      baicalein with flumazenil. Furthermore, the expressions level of BDNF was
      significantly increased in the baicalein with flumazenil-treated group compared
      to the baicalein- or flumazenil-treated groups in the hippocampus after an
      acquisition trial. These results suggest that the reasons why baicalein does not
      exert cognitive enhancement although it enhances the expression levels of pERK,
      pCREB, and BDNF are, in part, derived from its GABA(A) receptor agonistic
      property which is antagonized by flumazenil.

PMID- 20691673
TI  - MPTP-induced parkinsonism extends to a subclass of TH-positive neurons in the
      gut.
AB  - Gastrointestinal (GI) dysfunction occurs frequently in early Parkinson's disease
      (PD) and it is supposed to anticipate motor symptoms. About 80% of PD patients
      suffer from constipation before the onset of movement disorders. Despite such a
      high prevalence of gut impairment in PD, the molecular mechanisms remain poorly
      investigated. This is also due to the scarcity of experimental studies. In the
      present work, we tried to reproduce digestive abnormalities observed in PD
      patients by administering the parkinsonism-inducing neurotoxin 1-methyl-4-phenyl
      1,2,3,6,-tetrahydropyridine (MPTP) to C57BL mice. We show that in these mice,
      MPTP (20mg/kg * 3) while producing the classic striatal dopamine (DA)
      denervation, persistently delays colonic motility, produces constipation, and
      reduces the number of enteric TH-positive neurons. The loss of TH-positive cells
      in the gut is selectively due to the disappearance of DA neurons within both
      myenteric and mostly submucosal plexus in the intestine, while no change is
      detected in the esophagus and stomach. In contrast, norepinephrine (NE) neurons
      are not affected. These data were confirmed by immunohistochemistry and by HPLC
      showing the significant loss of DA levels while NE and 5-HT content was not
      affected. Dopamine cell loss was associated with increased alpha-synuclein
      levels. These functional, biochemical, and morphological findings extend the PD
      mimicking effects of MPTP to GI dysfunctions and provide a useful experimental
      model to understand gut dysfunction in PD and to find effective treatments for
      digestive symptoms.

PMID- 20691672
TI  - Effects of reverberation on brainstem representation of speech in musicians and
      non-musicians.
AB  - Perceptual and neurophysiological enhancements in linguistic processing in
      musicians suggest that domain specific experience may enhance neural resources
      recruited for language specific behaviors. In everyday situations, listeners are
      faced with extracting speech signals in degraded listening conditions. Here, we
      examine whether musical training provides resilience to the degradative effects
      of reverberation on subcortical representations of pitch and formant-related
      harmonic information of speech. Brainstem frequency-following responses (FFRs)
      were recorded from musicians and non-musician controls in response to the vowel
      /i/ in four different levels of reverberation and analyzed based on their spectro
      temporal composition. For both groups, reverberation had little effect on the
      neural encoding of pitch but significantly degraded neural encoding of formant
      related harmonics (i.e., vowel quality) suggesting a differential impact on the
      source-filter components of speech. However, in quiet and across nearly all
      reverberation conditions, musicians showed more robust responses than non
      musicians. Neurophysiologic results were confirmed behaviorally by comparing
      brainstem spectral magnitudes with perceptual measures of fundamental (F0) and
      first formant (F1) frequency difference limens (DLs). For both types of
      discrimination, musicians obtained DLs which were 2-4 times better than non
      musicians. Results suggest that musicians' enhanced neural encoding of acoustic
      features, an experience-dependent effect, is more resistant to reverberation
      degradation which may explain their enhanced perceptual ability on behaviorally
      relevant speech and/or music tasks in adverse listening conditions.

PMID- 20691674
TI  - Simvastatin enhances immune responses to Abeta vaccination and attenuates
      vaccination-induced behavioral alterations.
AB  - Statins are widely used to lower cholesterol levels by inhibiting cholesterol
      biosynthesis. Some evidence has indicated that statins might have therapeutic and
      preventive benefits for Alzheimer's disease (AD). We and others also have shown
      the beneficial effect of statin treatment in reversing learning and memory
      deficits in animal models of AD. However, data from clinical trials are
      inconclusive. We previously documented that the adenovirus vector encoding 11
      tandem repeats of Abeta1-6 fused to the receptor-binding domain (Ia) of
      Pseudomonas exotoxin A, AdPEDI-(Abeta1-6)(11), is effective in inducing an immune
      response against amyloid-beta protein (Abeta) and reducing brain Abeta load in
      Alzheimer's mouse models. In the present study, we examined whether the
      administration of simvastatin can modulate immune and behavioral responses of
      C57BL/6 mice to vaccination. Simvastatin was given to the animals as a diet
      admixture for four weeks, followed by nasal vaccination with AdPEDI-(Abeta1
      6)(11) once per week for four weeks. The cholesterol-lowering action of
      simvastatin was monitored by measuring the cholesterol levels in plasma.
      Simvastatin significantly increased the number of the mice responding to
      vaccination compared with the mice receiving only AdPEDI-(Abeta1-6)(11).
      Immunoglobulin isotyping revealed that the vaccination predominantly induced Th2
      immune responses. Simvastatin treatment prevented Abeta-induced production of IFN
      gamma in splenocytes. The adenovirus vaccination altered mouse behavior in T- and
      elevated plus-maze tests and simvastatin counteracted such behavioral changes.
      Our results indicate that simvastatin clearly enhances the immune responses of
      C57BL/6 mice to the nasal vaccination with AdPEDI-(Abeta1-6)(11). Simvastatin may
      be effective in preventing behavioral changes associated with vaccination.

PMID- 20691675
TI  - Children with reading difficulties show differences in brain regions associated
      with orthographic processing during spoken language processing.
AB  - We explored the neural basis of spoken language deficits in children with reading
      difficulty, specifically focusing on the role of orthography during spoken
      language processing. We used functional magnetic resonance imaging (fMRI) to
      examine differences in brain activation between children with reading
      difficulties (aged 9-to-15 years) and age-matched children with typical
      achievement during an auditory rhyming task. Both groups showed activation in
      bilateral superior temporal gyri (BA 42 and 22), a region associated with
      phonological processing, with no significant between-group differences.
      Interestingly, typically achieving children, but not children with reading
      difficulties, showed activation of left fusiform cortex (BA 37), a region
      implicated in orthographic processing. Furthermore, this activation was
      significantly greater for typically achieving children compared to those with
      reading difficulties. These findings suggest that typical children automatically
      activate orthographic representations during spoken language processing, while
      those with reading difficulties do not. Follow-up analyses revealed that the
      intensity of the activation in the fusiform gyrus was associated with
      significantly stronger behavioral conflict effects in typically achieving
      children only (i.e., longer latencies to rhyming pairs with orthographically
      dissimilar endings than to those with identical orthographic endings; jazz-has
      vs. cat-hat). Finally, for reading disabled children, a positive correlation
      between left fusiform activation and nonword reading was observed, such that
      greater access to orthography was related to decoding ability. Taken together,
      the results suggest that the integration of orthographic and phonological
      processing is directly related to reading ability.

PMID- 20691676
TI  - Potentiation of tumour promotion by topical application of argemone oil/isolated
      sanguinarine alkaloid in a model of mouse skin carcinogenesis.
AB  - Several incidences of adverse effects on human health have been reported in many
      countries, due to consumption of edible oil adulterated with argemone oil (AO).
      The clinical manifestation of the disease is commonly referred to as epidemic
      dropsy. Our prior studies have shown that AO and isolated sanguinarine alkaloid
      (SANG) possess genotoxic and tumour initiating activity. In this study, the
      effect of AO/SANG was investigated on the development of tumour formation in mice
      using 7,12-dimethylbenz (a) anthracene (DMBA) initiated followed by tetradecanoyl
      phorbol acetate (TPA)-promoted skin tumour protocol. Single application of AO
      (300MUl) or SANG (4.5MUmol) when used during initiation phase in DMBA/TPA group
      did not reveal substantial difference in tumourigenic response. However, twice
      weekly application of AO (100MUl) or SANG (1.5MUmol) during promotion phase (25
      weeks) resulted in enhanced tumourigenic response by >=30% in DMBA/TPA treated
      group along with significant decrease in dermal tyrosinase (45-49%), histidase
      (30-32%), superoxide dismutase (53-56%), catalase (41%), GSH reductase (37-40%)
      and GSH-peroxidase activity (29-33%) compared to control. Furthermore,
      significant decrease of epidermal GSH (64-66%) content and enhanced formation of
      lipid peroxides (96-121%) was noticed following AO or SANG treatment during
      promotion phase to DMBA/TPA induced animals indicating the modified pro-oxidant
      status in skin. Although dermal biochemical parameters were also altered by AO or
      SANG when used during initiation phase in DMBA/TPA treated animals, nonetheless,
      the response in these parameters were relatively more when AO or SANG were used
      during promotion phase in DMBA/TPA treated animals. These results clearly suggest
      that AO and SANG have the ability to enhance the tumourigenic response, which may
      have relevance to its carcinogenic potential.

PMID- 20691677
TI  - Investigation of the use of Pulse Tube in cell cryopreservation systems.
AB  - In order to obtain an acceptable rate of survival of the frozen cells, they must
      be first cooled in programmable freezers, while controlling the cooling rate, and
      then stored in maintenance freezers. Different solutions are already used to
      preserve cells at cryogenic temperatures without liquid nitrogen, while this is
      not true for controlling the cooling rate. A Pulse Tube (PT) cryorefrigeration
      system type, can be used in the automatic freezing if combined with a system that
      monitors and "drives" the temperature generated on the cold part (cold head). To
      make the Pulse Tube system a suitable one for freezing processes, the cooling
      curve must be "corrected" in a linear one with a slope given by requested cooling
      rate. The temperature regulation is obtained with the use of a power dissipator
      based on Joule effect. In this study, the power to be dissipated is calculated
      individualizing the trend of temperature on the Pulse Tube cold head and inside
      the cell test tubes. The control system is not based on an historical series of
      data so it can be used in different operative conditions. The obtained
      temperature curve is in good agreement with the theoretical values, with errors
      within those accepted by commercial systems. The Pulse Tube cryorefrigerator may
      represent a valid alternative solution to programmable liquid nitrogen freezer,
      especially where nitrogen's supply is difficult or extremely expensive.

PMID- 20691678
TI  - TMF/ARA160: A key regulator of sperm development.
AB  - TMF/ARA160 is a Golgi-associated protein to which several cellular activities
      have been attributed. These include, trafficking of Golgi-derived vesicles and E3
      ubiquitin ligase activity. Here we show that TMF/ARA160 is required for the onset
      of key processes which underlie the development of mature sperm in mammals.
      TMF/ARA160 is highly expressed in specific spermatogenic stages. While the
      protein is not detected in the spermatogenic progenitor cells - spermatogonia, it
      accumulates in the Golgi of spermatocytes and spermatids but then disappears and
      is absent from spermatozoa and epididymal sperm cells. Mice that are homozygous
      null for TMF develop normally are healthy and the females are fertile. However,
      the males are sterile and their spermatids suffer from several developmental
      defects. They lack homing of Golgi-derived proacrosomal vesicles to the
      perinuclear surface, resulting in spermatozoa and epididymal sperm cells which
      lack acrosome. In a later developmental stage, the cytoplasm is not properly
      removed, thus resulting in spermatids which bare the nucleus with tightly packed
      DNA, surrounded by a cytoplasm. Finally, the spermatozoa of TMF(-/-) mice also
      suffer from misshapen heads, tails coiling around the sperm heads, and lack of
      motility. Taken together our findings portray TMF/ARA160 as a key regulator which
      is essential for the onset of key events in the differentiation and maturation of
      mammalian sperm and whose absence severely compromises their ability to fertilize
      ova.

PMID- 20691680
TI  - Down-regulation of UDP-glucose dehydrogenase affects glycosaminoglycans synthesis
      and motility in HCT-8 colorectal carcinoma cells.
AB  - UDP-glucose dehydrogenase (UGDH) catalyzes oxidation of UDP-glucose to yield UDP
      glucuronic acid, a precursor of hyaluronic acid (HA) and other glycosaminoglycans
      (GAGs) in extracellular matrix. Although association of extracellular matrix with
      cell proliferation and migration has been well documented, the importance of UGDH
      in these behaviors is not clear. Using UGDH-specific small interference RNA to
      treat HCT-8 colorectal carcinoma cells, a decrease in both mRNA and protein
      levels of UGDH, as well as the cellular UDP-glucuronic acid and GAG production
      was observed. Treatment of HCT-8 cells with either UGDH-specific siRNA or HA
      synthesis inhibitor 4-methylumbelliferone effectively delayed cell aggregation
      into multicellular spheroids and impaired cell motility in both three-dimensional
      collagen gel and transwell migration assays. The reduction in cell aggregation
      and migration rates could be restored by addition of exogenous HA. These results
      indicate that UGDH can regulate cell motility through the production of GAG. The
      enzyme may be a potential target for therapeutic intervention of colorectal
      cancers.

PMID- 20691679
TI  - Dorsal eye selector pannier (pnr) suppresses the eye fate to define dorsal margin
      of the Drosophila eye.
AB  - Axial patterning is crucial for organogenesis. During Drosophila eye development,
      dorso-ventral (DV) axis determination is the first lineage restriction event. The
      eye primordium begins with a default ventral fate, on which the dorsal eye fate
      is established by expression of the GATA-1 transcription factor pannier (pnr).
      Earlier, it was suggested that loss of pnr function induces enlargement in the
      dorsal eye due to ectopic equator formation. Interestingly, we found that in
      addition to regulating DV patterning, pnr suppresses the eye fate by
      downregulating the core retinal determination genes eyes absent (eya), sine
      oculis (so) and dacshund (dac) to define the dorsal eye margin. We found that pnr
      acts downstream of Ey and affects the retinal determination pathway by
      suppressing eya. Further analysis of the "eye suppression" function of pnr
      revealed that this function is likely mediated through suppression of the
      homeotic gene teashirt (tsh) and is independent of homothorax (hth), a negative
      regulator of eye. Pnr expression is restricted to the peripodial membrane on the
      dorsal eye margin, which gives rise to head structures around the eye, and pnr is
      not expressed in the eye disc proper that forms the retina. Thus, pnr has dual
      function, during early developmental stages pnr is involved in axial patterning
      whereas later it promotes the head specific fate. These studies will help in
      understanding the developmental regulation of boundary formation of the eye field
      on the dorsal eye margin.

PMID- 20691681
TI  - Long-term changes in cerebellar activation during functional recovery from
      transient peripheral motor paralysis.
AB  - Localized altered cerebellar cortical activity can be associated with short-term
      changes in motor learning that take place in the course of hours, but it is
      unknown whether it can be correlated to long-term recovery from transient
      peripheral motor diseases, and if so, whether it occurs concomitantly in related
      brain regions. Here we show in a longitudinal fMRI study of patients with
      unilateral Bell's palsy that increases in ipsilateral cerebellar activity follow
      the recovery course of facial motor functions over at least one and a half years.
      These findings hold true for changes in brain activity related to both oral and
      peri-orbital activation, even though these processes are differentially mediated
      by unilateral and bilateral brain connectivities, respectively. Activation of non
      facial musculature, which was studied for control, does not show any change in
      cerebellar activity over time. The localized changes in cerebellar activities
      following activation of facial functions occur concomitantly with increases in
      activity of the facial region in the contralateral primary motor cortex
      suggesting that the cerebellum acts together with the cerebral cortex in long
      term adaptation to transient pathological sensorimotor processing.

PMID- 20691682
TI  - Morphological and physiological changes in Leishmania promastigotes induced by
      yangambin, a lignan obtained from Ocotea duckei.
AB  - We have previously demonstrated that yangambin, a lignan obtained from Ocotea
      duckei Vattimo (Lauraceae), shows antileishmanial activity against promastigote
      forms of Leishmania chagasi and Leishmania amazonensis. The aim of this study was
      to determine the in vitro effects of yangambin against these parasites using
      electron and confocal microscopy. L. chagasi and L. amazonensis promastigotes
      were incubated respectively with 50 MUg/mL and 65 MUg/mL of pure yangambin and
      stained with acridine orange. Treated-parasites showed significant alterations in
      fluorescence emission pattern and cell morphology when compared with control
      cells, including the appearance of abnormal round-shaped cells, loss of cell
      motility, nuclear pyknosis, cytoplasm acidification and increased number of
      acidic vesicular organelles (AVOs), suggesting important physiological changes.
      Ultrastructural analysis of treated-promatigotes showed characteristics of cell
      death by apoptosis as well as by autophagy. The presence of parasites exhibiting
      multiples nuclei suggests that yangambin may also affect the microtubule dynamic
      in both Leishmania species. Taken together our results show that yangambin is a
      promising agent against Leishmania.

PMID- 20691683
TI  - Ascaris suum: RNAi mediated silencing of enolase gene expression in infective
      larvae.
AB  - Ascaris suum is an important parasite of pigs that causes tremendous economic
      losses globally to agriculture and animal husbandry annually. RNA interference
      (RNAi) technology has been described as a successful and useful approach for the
      elucidation of gene function in parasitic nematodes. In the present study, RNAi
      was used to silence the expression of a gene encoding enolase in A. suum by
      soaking infective larvae in double-stranded RNA derived from an EST (representing
      As-enol-1) selected from an A. suum infective larvae-specific cDNA library. The
      mRNA levels of RNAi-treated larvae were examined by Reverse-Transcription PCR (RT
      PCR) analysis. The survival of RNAi-treated larvae was compared with larvae
      treated with dsRNA-free culture medium. The effect of enolase depletion on the
      development of A. suum larvae was assessed by infecting BALB/c mice with RNAi
      treated larvae. The results showed that enolase gene expression was silenced
      completely and the survival rate of the RNAi-treated nematodes was reduced by
      20.11% (P<0.01) after soaking for 72 h. Although no significant difference was
      detected in the numbers of larvae recovered from the liver and lungs of infected
      mice 4 days post infection, RNAi knockdown of the A. suum enolase mRNA led to
      significant shorter larvae, indicating that loss of enolase expression may cause
      delays in larval development.

PMID- 20691684
TI  - Isolation of a point-mutated p47 lacking binding affinity to p97ATPase.
AB  - p47, a p97-binding protein, functions in Golgi membrane fusion together with p97
      and VCIP135, another p97-binding protein. We have succeeded in creating p47 with
      a point mutation, F253S, which lacks p97-binding affinity. p47 mapping
      experiments revealed that p47 had two p97-binding regions and the F253S mutation
      occurred in the first p97-binding site. p47(F253S) could not form a complex with
      p97 and did not caused any cisternal regrowth in an in vitro Golgi reassembly
      assay. In addition, mutation corresponding to the p47 F253S mutation in p37 and
      ufd1 also abolished their binding ability to p97.

PMID- 20691685
TI  - Molecular characterization of beta1,4-galactosyltransferase 7 genetic mutations
      linked to the progeroid form of Ehlers-Danlos syndrome (EDS).
AB  - beta1,4-Galactosyltransferase 7 (beta4GalT7) is a key enzyme initiating
      glycosaminoglycan (GAG) synthesis. Based on in vitro and ex vivo kinetics studies
      and structure-based modelling, we molecularly characterized beta4GalT7 mutants
      linked to the progeroid form of Ehlers-Danlos syndrome (EDS), a severe connective
      tissue disorder. Our results revealed that loss of activity upon L206P
      substitution due to altered protein folding is the primary cause for the GAG
      synthesis defect in patients carrying the compound A186D and L206P mutations. We
      showed that R270C substitution strongly reduced beta4GalT7 affinity towards
      xyloside acceptor, thus affecting GAG chains formation. This study establishes
      the molecular basis for beta4GalT7 defects associated with altered GAG synthesis
      in EDS.

PMID- 20691686
TI  - Extracellular signal-regulated kinase (ERK) participates in the hypercapnia
      induced Na,K-ATPase downregulation.
AB  - Hypercapnia has been shown to impair alveolar fluid reabsorption (AFR) by
      decreasing Na,K-ATPase activity. Extracellular signal-regulated kinase pathway
      (ERK) is activated under conditions of cellular stress and has been known to
      regulate the Na,K-ATPase. Here, we show that hypercapnia leads to ERK activation
      in a time-dependent manner in alveolar epithelial cells (AEC). Inhibition of ERK
      by U0126 or siRNA prevented both the hypercapnia-induced Na,K-ATPase endocytosis
      and impairment of AFR. Moreover, ERK inhibition prevented AMPK activation, a
      known modulator of hypercapnia-induced Na,K-ATPase endocytosis. Accordingly,
      these data suggest that hypercapnia-induced Na,K-ATPase endocytosis is dependent
      on ERK activation in AEC and that ERK plays an important role in hypercapnia
      induced impairment of AFR in rat lungs.

PMID- 20691687
TI  - Cyclic cytidine 3',5'-monophosphate (cCMP) signals via cGMP kinase I.
AB  - We analysed the function and intracellular signalling of the cyclic pyrimidinic
      nucleotide cCMP. The membrane-permeable cCMP analogue dibutyryl-cCMP mediated
      mouse aorta relaxation. cCMP activated purified cGMP-dependent protein kinase
      (cGK) Ialpha and Ibeta and stimulated cGK in aorta lysates. cCMP-induced
      relaxation was abolished in cGKI-knockout tissue. Additionally, deletion of
      inositol-trisphosphate receptor associated cGKI substrate (IRAG) suppressed cCMP
      mediated relaxation. Signalling of cCMP via cGKI/IRAG appears to be of broader
      physiological importance because cCMP-mediated inhibition of platelet aggregation
      was absent in cGKI- and IRAG-deficient platelets. These results demonstrate that
      cCMP acts as intracellular messenger molecule, most unexpectedly utilizing the
      cGMP signal transduction pathway.

PMID- 20691688
TI  - The correlation coefficient of GC content of the genome-wide genes is positively
      correlated with animal evolutionary relationships.
AB  - In this study, we present a new method for evaluating animal evolutionary
      relationships. We used the GC% levels of genome-wide genes to determine the
      correlation between the GC% content and evolutionary relationship. The
      correlation coefficients of the GC% content of the orthologous genes of the
      paired animal species were calculated for a total of 21 species, and the
      evolutionary branching dates of these 21 species were derived from fossil
      records. The correlation coefficient of the GC% content of the orthologous genes
      of the species pair under study served as an indicator of their evolutionary
      relationship. Moreover, there was a decreasing linear relationship between the
      correlation coefficient and evolutionary branching date (R(2)=0.930).

PMID- 20691690
TI  - Tissue-specific promoter methylation coincides with Cyp19 gene expression in
      buffalo (Bubalus bubalis) placenta of different stages of gestation.
AB  - Aromatase is the key enzyme for estrogen biosynthesis and is encoded by Cyp19
      gene. Placental cotyledons are the main site of Cyp19 gene expression during
      pregnancy. The present study was aimed to investigate if DNA methylation and thus
      epigenetic mechanisms play a potential role in stage-specific regulation of Cyp19
      expression in placental cotyledons of pregnant water buffaloes (Bubalus bubalis).
      Significantly higher expression of Cyp19 gene (p<0.05) in placental cotyledons of
      early gestation period and post parturition period was found in comparison to mid
      gestation placenta. Tissue-specific promoter driven transcript analyses showed
      that the change in expression was mainly due to change in the relative abundance
      of transcripts from exon I.1 while the transcripts from exon II showed
      comparatively less variation. Methylation analysis of 5 CpG dinucleotides of
      placenta-specific promoter I.1 and proximal promoter, PII showed hypo-methylation
      of PI.1 in early and term placenta while hyper-methylation in mid-placenta.
      However, PII was found to be hypomethylated in all the three tissues. In
      conclusion, result of the present study demonstrated that stage-specific
      methylation status of PI.1, the major promoter responsible for aromatase
      expression in buffalo placental cotyledons, coincides with the change in
      expression of Cyp19 gene in different stages of pregnancy.

PMID- 20691689
TI  - Chenodeoxycholate in females with irritable bowel syndrome-constipation: a
      pharmacodynamic and pharmacogenetic analysis.
AB  - BACKGROUND & AIMS: Sodium chenodeoxycholate (CDC) accelerates colonic transit in
      health. Our aim was to examine pharmacodynamics (colonic transit, bowel function)
      and pharmacogenetics of CDC in constipation-predominant irritable bowel syndrome
      (IBS-C). METHODS: In a double-blind placebo-controlled study, 36 female patients
      with IBS-C were randomized to treatment with delayed-release oral formulations of
      placebo, 500 mg CDC, or 1000 mg CDC for 4 days. We assessed gastrointestinal and
      colonic transit, stool characteristics, and associations of transit with fasting
      serum 7alphaC4 (surrogate of bile acid synthesis) and FGF19 (negative regulator
      of bile acid synthesis) levels. Candidate genetic polymorphisms involved in
      regulation of bile acid synthesis were analyzed in the 36 patients with IBS-C and
      57 healthy volunteers to assess genetic influence on effects of CDC on transit.
      RESULTS: Overall colonic transit and ascending colon emptying (AC t(1/2)) were
      significantly accelerated in the CDC group compared with placebo (P = .005 and P
      = .028, respectively). Looser stool consistency (P = .003), increased stool
      frequency (P = .018), and greater ease of passage (P = .024) were noted with CDC
      compared with placebo. The most common side effect was lower abdominal
      cramping/pain (P = .01). Fasting serum 7alphaC4 (but not FGF19) was positively
      associated with colonic transit (r(s) = 0.749, P = .003, placebo group). Genetic
      variation in FGFR4 was associated with AC t(1/2) in response to CDC (uncorrected
      P = .015); alphaKlothobeta variant showed a gene-by-treatment interaction based
      on patient subgroup (uncorrected P = .0088). CONCLUSIONS: CDC accelerates colonic
      transit and improves bowel function in female patients with IBS-C. The rate of
      bile acid synthesis influences colonic transit. Genetic variation in negative
      feedback inhibition of bile acid synthesis may affect CDC-mediated acceleration
      of colonic transit.

PMID- 20691691
TI  - Identification and expression of mRNAs encoding bursicon in the plesiomorphic
      central nervous system of Homarus gammarus.
AB  - Ecdysis in arthropods is a complex process, regulated by many neurohormones,
      which must be released in a precisely coordinated manner. In insects, the
      ultimate hormone involved in this process is the cuticle tanning hormone,
      bursicon. Recently, this hormone has been identified in crustaceans. To further
      define the distribution of bursicon in crustacean nervous systems, and to compare
      hormone structures within the sub-phylum, cDNAs encoding both bursicon subunits
      were cloned and sequenced from the nervous system of the European lobster,
      Homarus gammarus, and expression patterns including those for CCAP determined
      using in-situ hybridisation, quantitative RT-PCR and immunohistochemistry. Full
      length cDNAs encoded bursicon subunits of 121 amino acids (Average M(r):
      13365.48) for Burs alpha, 115 amino acids (Average M(r): 12928.54) for Burs beta.
      Amino acid sequences were most closely related to those of crabs, and for Burs
      beta the sequence was identical to that of the American lobster, Homarus
      americanus. Complete co-localisation with CCAP in the VNC was seen. Copy numbers
      burs alpha, burs beta and CCAP mRNAs were between 0.5 and 1.5 * 10(5) for both
      bursicon subunits, 0.5-6 * 10(5) per cdn neurone for CCAP. The terminal abdominal
      ganglia (AG 6-8) contained about 52 cdn-type neurons, making it the largest
      bursicon producing region in the CNS. Double labelling IHC using recombinant
      Carcinus Burs alpha and CCAP antisera demonstrated complete co-localisation in
      the VNC. On the basis of the results obtained, it is proposed that CCAP and
      bursicon release occur simultaneously during ecdysis in crustaceans.

PMID- 20691693
TI  - Long-term ovariectomy enhances anxiety and depressive-like behaviors in mice
      submitted to chronic unpredictable stress.
AB  - Ovarian hormones exert anti-depressive and anxiolytic actions. In this study we
      have analyzed the effects of ovariectomy on the development of anxiety and
      depression-like behaviors and on cell proliferation in the hippocampus of mice
      submitted to chronic unpredictable stress. Animals submitted to stress 4 months
      after ovariectomy showed a significant increase in immobility behavior in the
      forced swimming test compared to animals submitted to stress 2 weeks after
      ovariectomy. In addition, long-term ovariectomy resulted in a significant
      decrease on the time spent in the open arms in the elevated plus-maze test
      compared to control animals. Stress did not significantly affect cell
      proliferation in the hilus of the dentate gyrus. However, ovariectomy resulted in
      a significant decrease in cell proliferation. These results indicate that long
      term deprivation of ovarian hormones enhances the effect of chronic unpredictable
      stress on depressive- and anxiety-like behaviors in mice. Therefore, a prolonged
      deprivation of ovarian hormones may represent a risk factor for the development
      of depressive and anxiety symptoms after the exposure to stressful experiences.

PMID- 20691692
TI  - Gestational exposure to bisphenol A and cross-fostering affect behaviors in
      juvenile mice.
AB  - Bisphenol-A (BPA) is a component of polycarbonate resins, and, lately, concern
      has been raised about its potential negative effects on human health. BPA is an
      estrogen analog and, in addition, it can act as a DNA hypomethylator. We examined
      the effects of gestational exposure to BPA on several behaviors in C57BL/6J mice.
      Because BPA affects maternal care, which, may have long-lasting effects on
      offspring behavior, we tested mice raised by either biological or fostered dams.
      Both diet and dam affected behavior in juvenile mice in a social novelty task and
      the elevated plus maze (EPM). In a social novelty task, the amount of time spent
      interacting with an adult male was affected by sex and gestational diet, but only
      in juveniles raised by a foster dam. Control females spent less time sniffing a
      novel adult than did control males or females exposed to BPA during gestation. In
      the EPM, juveniles reared by foster dams and exposed to BPA during gestation
      spent less time in the distal half of the open arm as compared with juveniles
      gestated on a control diet. Adult offspring raised by their biological dams
      showed the same response pattern; gestational BPA increased anxiety as compared
      with control diet. Our results show that prenatal BPA exposure affects social
      behavior and anxiety in the EPM. Moreover, some facet(s) of the infant-maternal
      interaction may modify these effects.

PMID- 20691694
TI  - Low luteinizing hormone enhances spatial memory and has protective effects on
      memory loss in rats.
AB  - Though several studies have suggested that estradiol improves hippocampal
      dependent spatial memory, the effects of other hormones in the hypothalamic
      pituitary-gonadal axis on memory have largely been ignored. Estradiol and
      luteinizing hormone (LH) are generally inversely related and LH may significantly
      affect spatial memory. Ovariectomized (ovx) rats treated with Antide (a
      gonadotropin releasing hormone receptor antagonist) had low LH levels and showed
      enhanced spatial memory, comparable to treatment with estradiol. Antide-treated
      ovx females retained spatial memory longer than estradiol-treated ovx females.
      Deficits in spatial memory are a primary symptom of neurodegenerative disorders
      including Alzheimer's disease (AD). Treatment with Antide prevented spatial
      memory deficits in a neurotoxin-induced model typical of early AD. These data
      suggest that memory impairments seen in female rats after ovariectomy or women
      after menopause may be due to high LH levels and that a reduction in LH enhances
      memory. These results also implicate an LH lowering agent as a potential
      preventative therapy for AD.

PMID- 20691695
TI  - Immunohistochemical detection of soluble immunoglobulins in living mouse small
      intestines using an in vivo cryotechnique.
AB  - Some morphological changes are inevitable during immersion- or perfusion-fixation
      and following alcohol-dehydration for tissue preparations. Common immunostaining
      techniques for these specimens have some limitations to capture accurate
      localizations of soluble proteins in cells and tissues. In this study, to examine
      in situ distributions of immunoglobulins (Igs), small intestinal tissues of
      living mice were prepared with our "in vivo cryotechnique" (IVCT). Thin sections
      were first stained with hematoxylin-eosin for morphology, and then some
      immunostainings were performed on serial sections for IgA, Ig kappa light chain,
      IgG1 heavy chain (IgG1), and IgM. Living morphological states of small intestinal
      tissues, including flowing erythrocytes and opening blood vessels, were observed
      on paraffin sections prepared with IVCT. IgA was immunolocalized in many plasma
      cells of the lamina mucosa propria, intestinal matrices, and also in epithelial
      cells of the intestinal villi and crypts. Both IgG1 and IgM immunoreactivities
      were mainly detected in blood vessels, whereas only IgG1 was also immunolocalized
      in interstitial matrices of mucous membranes. By perfusion-fixation and alcohol
      dehydration, however, IgA immunoreactivity was observed in plasma cells, but not
      in epithelial cells or the lamina mucosa propria. Thus, IVCT was more useful to
      examine in vivo immunolocalizations of soluble Igs in small intestines.

PMID- 20691697
TI  - Hematodinium sp. infection of red Paralithodes camtschaticus and blue
      Paralithodes platypus king crabs from the Sea of Okhotsk, Russia.
AB  - A disease caused by a parasitic dinoflagellate of the genus Hematodinium was
      identified in red, Paralithodes camtschaticus, and blue, Paralithodes platypus,
      king crabs from the north-east region of the Sea of Okhotsk, Russia, during
      annual stock surveys. No carapace color change was observed even in heavily
      infected crabs, but diseased crabs possessed creamy-yellow hemolymph, which was
      visible through the arthrodial membranes of the abdomen and appendages. Several
      stages of the parasite's life history, including trophonts, plasmodia, sporonts
      and macrodinospores, were observed in tissues of infected king crabs. Numerous
      parasite cells were observed in the lumina of the myocardium, the gills, the
      connective tissue of antennal glands and the sinuses of nerve ganglia, eyestalks
      and gastrointestinal tract of king crabs with gross signs of infection. Based on
      sequencing of the 18S rDNA, it appears that the Hematodinium sp. found in red and
      blue king crabs is identical or closely related to Hematodinium sp. isolated from
      crabs of the genera Chionoecetes and Lithodes. Observed prevalences were 0.33% in
      sublegal male red king crabs, 0.18% in female red king crabs, 0.34% in sublegal
      male blue king crabs and 0.31% in female blue king crabs.

PMID- 20691696
TI  - Neutrophil activation during transmigration in vivo and in vitro A translational
      study using the skin chamber model.
AB  - Neutrophil transmigration can be studied in vitro by use of the transwell model
      and in vivo by the skin chamber model. Activation during transmigration involves
      translocation of secretory vesicles and granules to the plasma- and phagolysosome
      membranes. In this study, we compared the skin chamber model with the transwell
      model, focusing on the mobilization of CR1 (CD35), CR3 (CD11b/CD18) and CD63 from
      intracellular vesicles and granules. In addition, functional responses towards a
      bacterial related stimulus, formyl-methionyl-leucyl-phenylalanine (fMLP), in
      terms of CR3 expression and production of reactive oxygen species (ROS) were
      assessed. Discrepancies between the skin chamber model and the transwell model
      were observed. The expression of CR1 increased following in vivo transmigration
      (p<0.001) and, in contrast, decreased following in vitro transmigration
      (p=0.004). Furthermore, CR1 was mobilized following an isolation procedure
      included in the transwell model. The expression of CR3 increased following both
      in vivo (p<0.001) and in vitro (p=0.03) transmigration. However, in vitro
      transmigration did not influence the fMLP induced CR3 expression which was
      significantly increased following in vivo transmigration (p=0.01). In addition,
      the fMLP induced production of ROS was significantly reduced following in vitro
      transmigration (p=0.002) but unaltered after in vivo transmigration, indicating
      differences between the impact of the two systems on cellular activation. The
      observed discrepancies between the two models might be partly explained by
      granule mobilization and neutrophil priming, induced during the isolation
      procedure included in the transwell model, which results in an altered cellular
      activation. Therefore, mobilization of granules needs to be accounted for when
      interpreting data from different model systems.

PMID- 20691698
TI  - Inhibition of Rho-ROCK signaling induces apoptotic and non-apoptotic PS exposure
      in cardiomyocytes via inhibition of flippase.
AB  - Subsequent to myocardial infarction, cardiomyocytes within the infarcted areas
      and border zones expose phosphatidylserine (PS) in the outer plasma membrane
      leaflet (flip-flop). We showed earlier that in addition to apoptosis, this flip
      flop can be reversible in cardiomyocytes. We now investigated a possible role for
      Rho and downstream effector Rho-associated kinase (ROCK) in the process of
      (reversible) PS exposure and apoptosis in cardiomyocytes. In rat cardiomyoblasts
      (H9c2 cells) and isolated adult ventricular rat cardiomyocytes Clostridium
      difficile Toxin B (TcdB), a Rho GTPase family inhibitor, C3 transferase (C3), a
      Rho(A,B,C) inhibitor and the ROCK inhibitors Y27632 and H1152 were used to
      inhibit Rho-ROCK signaling. PS exposure was assessed via flow cytometry and
      fluorescent digital imaging microscopy using annexin V. Akt expression and
      phosphorylation were analyzed via Western blot, and Akt activity was inhibited by
      wortmannin. The cellular concentration activated caspase 3 was determined as a
      measure of apoptosis, and flippase activity was assessed via flow cytometry using
      NBD-labeled PS. TcdB, C3, Y27632 and H1152 all significantly increased PS
      exposure. TcdB, Y27632 and H1152 all significantly inhibited phosphorylation of
      the anti-apoptotic protein Akt and Akt inhibition by wortmannin lead to increased
      PS exposure. However, only TcdB and C3, but not ROCK- or Akt inhibition led to
      caspase 3 activation and thus apoptosis. Notably, pancaspase inhibitor zVAD only
      partially inhibited TcdB-induced PS exposure indicating the existence of
      apoptotic and non-apoptotic PS exposure. The induced PS exposure coincided with
      decreased flippase activity as measured with NBD-labeled PS flip-flop. In this
      study, we show a regulatory role for a novel signaling route, Rho-ROCK-flippase
      signaling, in maintaining asymmetrical membrane phospholipid distribution in
      cardiomyocytes.

PMID- 20691700
TI  - A structural model for the DEAD box helicase YxiN in solution: localization of
      the RNA binding domain.
AB  - DEAD box proteins consist of a common helicase core formed by two globular RecA
      domains that are separated by a cleft. The helicase core acts as a nucleotide
      dependent switch that alternates between open and closed conformations during the
      catalytic cycle of duplex separation, thereby providing basic helicase activity.
      Flanking domains can direct the helicase core to a specific RNA substrate by
      mediating high-affinity or high-specificity RNA binding. In addition, they may
      position RNA for the helicase core or may directly contribute to unwinding. While
      structures of different helicase cores have been determined previously, little is
      known about the orientation of flanking domains relative to the helicase core.
      YxiN is a DEAD box protein that consists of a helicase core and a C-terminal RNA
      binding domain (RBD) that mediates specific binding to hairpin 92 in 23S rRNA. To
      provide a framework for understanding the functional cooperation of the YxiN
      helicase core and the RBD, we mapped the orientation of the RBD in single
      molecule fluorescence resonance energy transfer experiments. We present a model
      for the global conformation of YxiN in which the RBD lies above a slightly
      concave patch that is formed by flexible loops on the surface of the C-terminal
      RecA domain. The orientation of the RBD is different from the orientations of
      flanking domains in the Thermus thermophilus DEAD box protein Hera and in
      Saccharomyces cerevisiae Mss116p, in line with the different functions of these
      DEAD box proteins and of their RBDs. Interestingly, the corresponding patch on
      the C-terminal RecA domain that is covered by the YxiN RBD is also part of the
      interface between the translation factors eIF4A and eIF4G. Possibly, this region
      constitutes an adaptable interface that generally allows for the interaction of
      the helicase core with additional domains or interacting factors.

PMID- 20691699
TI  - The role of L1 stalk-tRNA interaction in the ribosome elongation cycle.
AB  - The ribosomal L1 stalk is a mobile structure implicated in directing tRNA
      movement during translocation through the ribosome. This article investigates
      three aspects of L1 stalk-tRNA interaction. First, by combining data from cryo
      electron microscopy, X-ray crystallography, and molecular dynamics simulations
      through the molecular dynamics flexible fitting method, we obtained atomic models
      of different tRNAs occupying the hybrid P/E state interacting with the L1 stalk.
      These models confirm the assignment of fluorescence resonance energy transfer
      states from previous single-molecule investigations of L1 stalk dynamics. Second,
      the models reconcile how initiator tRNA(fMet) interacts less strongly with the L1
      stalk compared to elongator tRNA(Phe), as seen in previous single-molecule
      experiments. Third, results from a simulation of the entire ribosome in which the
      L1 stalk is moved from a half-closed conformation to its open conformation are
      found to support the hypothesis that L1 stalk opening is involved in tRNA release
      from the ribosome.

PMID- 20691701
TI  - Measuring "unmeasurable" folding kinetics of proteins by single-molecule force
      spectroscopy.
AB  - Folding and unfolding are fundamental biological processes in cell and are
      important for the biological functions of proteins. Characterizing the folding
      and unfolding kinetics of proteins is important for understanding the energetic
      landscape leading to the active native conformations of these molecules. However,
      the thermal or chemical-induced unfolding of many proteins is irreversible in
      vitro, precluding characterization of the folding kinetics of such proteins, just
      as it is impossible to "un-boil" an egg. Irreversible unfolding often manifests
      as irreversible aggregation of unfolded polypeptide chains, which typically
      occurs between denatured protein molecules in response to the exposure of
      hydrophobic residues to solvent. An example of such a protein where thermal
      denaturation results in irreversible aggregation is the beta-1,4 endoxylanase
      from Bacillus circulans (BCX). Here, we report the use of single-molecule atomic
      force microscopy to directly measure the folding kinetics of BCX in vitro. By
      mechanically unfolding BCX, we essentially allowed only one unfolded molecule to
      exist in solution at a given time, effectively eliminating the possibility for
      aggregation. We found that BCX can readily refold back to the native state,
      allowing us to measure its folding kinetics for the first time. Our results
      demonstrate that single-molecule force-spectroscopy-based methods can adequately
      tackle the challenge of "un-boiling eggs", providing a general methodology to
      characterize the folding kinetics of many proteins that suffer from irreversible
      denaturation and thus cannot be characterized using traditional equilibrium
      methodologies.

PMID- 20691702
TI  - Crystal structures of the multidrug binding repressor Corynebacteriumglutamicum
      CgmR in complex with inducers and with an operator.
AB  - CgmR (CGL2612) from Corynebacterium glutamicum is a multidrug-resistance-related
      transcription factor belonging to the TetR family, which is a protein family of
      widespread bacterial transcription factors typically involved in environmental
      response. Here, we report the crystal structures of CgmR homodimeric repressor in
      complex with two distinct inducers (1.95 and 1.4 A resolution) and with an
      operator (2.5 A resolution). The CgmR-operator complex showed that two CgmR
      dimers bound to the operator, and each half-site of the palindromic operator was
      asymmetrically recognized by two DNA-binding domains from different dimers on the
      opposite sides of the DNA. The inducer complexes demonstrated that both bound
      inducers act as a wedge to alter the operator-binding conformation of the
      repressor by steric inhibition. As steric hindrance is used, various drugs should
      act as inducers if they have sufficient volume for the conformation change and if
      their bindings sufficiently reduce free energy. The comparative structural study
      of CgmR free protein, in complex with operator, and with inducers, implies the
      other mechanism that might contribute to multidrug response of the repressor.

PMID- 20691703
TI  - Using underdominance to bi-stably transform local populations.
AB  - Underdominance refers to natural selection against individuals with a
      heterozygous genotype. Here, we analyze a single-locus underdominant system of
      two large local populations that exchange individuals at a certain migration
      rate. The system can be characterized by fixed points in the joint allele
      frequency space. We address the conditions under which underdominance can be
      applied to transform a local population that is receiving wildtype immigrants
      from another population. In a single population, underdominance has the benefit
      of complete removal of genetically modified alleles (reversibility) and
      coexistence is not stable. The two population system that exchanges migrants can
      result in internal stable states, where coexistence is maintained, but with
      additional release of wildtype individuals the system can be reversed to a fully
      wildtype state. This property is critically controlled by the migration rate. We
      approximate the critical minimum frequency required to result in a stable
      population transformation. We also concentrate on the destabilizing effects of
      fitness and migration rate asymmetry. Practical implications of our results are
      discussed in the context of utilizing underdominance to genetically modify wild
      populations. This is of importance especially for genetic pest management
      strategies, where locally stable and potentially reversible transformations of
      populations of disease vector species are of interest.

PMID- 20691704
TI  - SecretP: identifying bacterial secreted proteins by fusing new features into
      Chou's pseudo-amino acid composition.
AB  - Protein secretion plays an important role in bacterial lifestyles. Secreted
      proteins are crucial for bacterial pathogenesis by making bacteria interact with
      their environments, particularly delivering pathogenic and symbiotic bacteria
      into their eukaryotic hosts. Therefore, identification of bacterial secreted
      proteins becomes an important process for the study of various diseases and the
      corresponding drugs. In this paper, fusing several new features into Chou's
      pseudo-amino acid composition (PseAAC), two support vector machine (SVM)-based
      ternary classifiers are developed to predict secreted proteins of Gram-negative
      and Gram-positive bacteria. For the two types of bacteria, the high accuracy of
      94.03% and 94.36% are obtained in distinguishing classically secreted, non
      classically secreted and non-secreted proteins by our method. In order to compare
      the practical ability of our method in identifying bacterial secreted proteins
      with those of six published methods, proteins in Escherichia coli and Bacillus
      subtilis are collected to construct the test sets of Gram-negative and Gram
      positive bacteria, and the prediction results of our method are comparable to
      those of existing methods. When performed on two public independent data sets for
      predicting NCSPs, it also yields satisfactory results for Gram-negative bacterial
      proteins. The prediction server SecretP can be accessed at
      http://cic.scu.edu.cn/bioinformatics/secretPV2/index.htm.

PMID- 20691706
TI  - Diselenium, instead of disulfide, bonded analogs of conotoxins: novel synthesis
      and pharmacotherapeutic potential.
AB  - The venoms of the cone snail (Conus) contain toxic peptides (conotoxins) that
      have remarkable selectivity for subtypes of a variety of mammalian voltage- and
      ligand-gated ion channels, G protein-coupled receptors, and neurotransmitter
      transporters. They thus have tremendous potential as pharmacologic tools. Less
      toxic analogs or mimetics could be highly-selective pharmacotherapeutic agents at
      their target sites. For this reason, conopeptides have been extensively studied
      and have progressed to clinical trials and even regulatory approval. However, the
      synthesis of the peptides remains difficult and stability and toxicity remain
      problems. A novel synthesis and testing of analogs incorporating diselenium bonds
      between selenocysteine residues in place of disulfide bonds between cysteine
      residues has recently been reported. The technique results in analogs that retain
      the folding of the native peptides, are more potent, and have the same or greater
      biological activity.

PMID- 20691705
TI  - Cardiac atria are the primary source of ANP release in hypoxia-adapted rats.
AB  - AIMS: atrial natriuretic peptide (ANP) is released from the heart in response to
      hypoxia and helps mitigate the development of pulmonary hypertension. However,
      the mechanism of hypoxia-induced ANP release is not clear. The cardiac atria are
      the primary source of ANP secretion under normal conditions, but right
      ventricular ANP expression is markedly up-regulated during adaptation to hypoxia.
      We sought to better understand mechanisms of cardiac ANP release during
      adaptation to hypoxia. MAIN METHODS: we measured hypoxia-induced ANP release from
      isolated perfused rat hearts obtained from normoxia and hypoxia-adapted rats
      before and after removal of the atria. KEY FINDINGS: in both normoxia- and
      hypoxia-adapted hearts, ANP levels in the perfusate increased within 15 min of
      hypoxia. Hypoxia-induced ANP release was greater from hypoxia-adapted than
      normoxia-adapted hearts. Baseline and hypoxia-induced ANP release were
      considerably greater with the atria intact (213+/-29 to 454+/-62 and 281+/-26 to
      618+/-87 pg/ml for normoxia- and hypoxia-adapted hearts respectively, P<0.001 for
      both) than with atria removed (94+/-17 to 131+/-32 and 103+/-26 to 201+/-55
      pg/ml, respectively, P<0.002 for both). Hypoxia-induced ANP release was reduced
      over 80% by removing the atria in both normoxia- and in hypoxia-adapted hearts.
      Acute hypoxia caused a transient increase in lactate release and reductions in pH
      and left ventricular generated force, but no differences in pH or left
      ventricular generated force were seen between normoxia- and hypoxia-adapted rats.
      SIGNIFICANCE: we conclude that the right ventricle is not a major source of
      cardiac ANP release in normoxia- or hypoxia-adapted rats.

PMID- 20691707
TI  - Tissue viability imaging for assessment of pharmacologically induced vasodilation
      and vasoconstriction in human skin.
AB  - Tissue viability imaging (TIVI) is a novel polarization spectroscopy method for
      assessing dermal vascular viability. The purpose of the present study was to
      compare TIVI with laser Doppler flowmetry (LDF) for assessment of
      pharmacologically induced vasodilation and vasoconstriction in human skin. Eight
      individual skin sites on the backs of seven healthy volunteers were randomized to
      receive an intradermal injection of prostaglandin E2 (PGE2, 10(-6) to 10(-9)M),
      norepinephrine (NE, 10(-5) to 10(-7)M), or vehicle. Vascular responses were
      measured by TIVI and LDF at the injection sites at 1-min intervals starting 2min
      before and ending 15min after the skin challenge. TIVI and LDF demonstrated
      significant dose-dependent and time-related vasodilator responses to PGE2 and
      vasoconstrictor responses to NE, respectively (p<0.001). The time course and dose
      response functions for LDF and TIVI showed notable differences. Dose-response
      data showed a significant reduction in TIVI signal with NE 10-7M (10(-6) NE with
      LDF) whereas PGE2 10(-6)M was required to elicit a significant increase in TIVI
      signal (10(-8)M PGE2 with LDF). TIVI demonstrated relative vascular response
      changes of 0.79 to 1.63 of baseline values at 15min with NE 10(-5)M or PGE2 10(
      6)M compared to values of 0.59 to 8.38 with LDF. There was a modest though
      significant correlation between relative changes in vascular responses measured
      by the two methods (p<0.0001, r(2)=0.521). A Bland-Altman difference plot
      demonstrated significant underestimation of relative increase versus baseline
      measured by TIVI (r(2)=0.99, p<0.0001). We conclude that TIVI polarization
      spectroscopy is a sensitive method for measurement of NE-induced vascular
      responses but that it is less sensitive than LDF for measurement of the PGE2
      induced reactions.

PMID- 20691708
TI  - The Leu7Pro polymorphism of the signal peptide of neuropeptide Y (NPY) gene is
      associated with increased levels of inflammatory markers preceding vascular
      complications in patients with type 2 diabetes.
AB  - AIMS/HYPOTHESIS: The Leucine7 to Proline7 (Leu7Pro) polymorphism of the signal
      peptide of neuropeptide Y (NPY) increases risk for vascular complications in
      diabetes. Diabetes is associated with low-grade inflammation, which has an
      important role in the development of atherosclerosis. Currently, we followed
      diabetes patients to investigate, if the Pro7 allele is associated with the
      inflammation related to atherosclerosis. METHODS: In the 5-year follow-up, the
      genotyped, pair-matched type 2 diabetes patients (12 with the Pro7 allele and 19
      without) were investigated using non-invasive ultrasound based methods to measure
      the development of atherosclerosis (intima media thickness=IMT) and endothelium
      dependent (FMD) and -independent nitrate-mediated (NMD) vasodilatation. The
      development of diabetic complications was followed annually, and the
      concentrations of inflammatory markers and NPY in plasma were determined.
      RESULTS: Patients with the Pro7 had increased U-albumin/creatinine (p=0.037), E
      selectin (p=0.016), fasting insulin (p=0.011) and HOMA index (p=0.013) but
      decreased serum amyloid P concentrations (p=0.021). Furthermore, men with the
      Pro7 had increased CRP (p=0.010) and NPY (p=0.026) concentrations. IMT and FMD
      were similar in all patients, however, NMD decreased more during the follow-up in
      the patients with the Pro7 (p=0.002). NPY correlated positively with bIMT [r 0.04
      (SE 0.02), p=0.007] and E-selectin negatively with FMD [r -0.05 (S.E 0.02),
      p=0.039]. CONCLUSIONS/INTERPRETATIONS: Diabetes patients with the Pro7 allele
      display increased levels of inflammatory molecules and NPY in blood, preceding
      vascular wall thickening and impaired endothelial dilatation, especially in male
      patients.

PMID- 20691709
TI  - Live cell imaging of micronucleus formation and development.
AB  - The micronucleus (MN) test is widely used to biomonitor humans exposed to
      clastogens and aneugens, but little is known about MN development. Here we used
      confocal time-lapse imaging and a fluorescent human lymphoblastoid cell line
      (T105GTCH), in which histone H3 and alpha-tubulin stained differentially, to
      record the emergence and behavior of micronuclei (MNi) in cells exposed to MN
      inducing agents. In mitomycin C (MMC)-treated cells, MNi originated in early
      anaphase from lagging chromosome fragments just after chromosome segregation. In
      gamma-ray-treated cells showing multipolar cell division, MN originated in late
      anaphase from lagging chromosome fragments generated by the abnormal cell
      division associated with supernumerary centrosomes. In vincristine(VC)-treated
      cells, MN formation was similar to that in MMC-treated cells, but MNi were also
      derived from whole chromosomes that did not align properly on the metaphase
      plate. Thus, the MN formation process induced by MMC, gamma-rays, and VC, were
      strikingly different, suggesting that different mechanisms were involved. MN
      stability, however, was similar regardless of the treatment and unrelated to MN
      formation mechanisms. MNi were stable in daughter cells, and MN-harboring cells
      tended to die during cell cycle progression with greater frequency than cells
      without MN. Because of their persistence, MN may have significant impact on
      cells, causing genomic instability and abnormally transcribed genes.

PMID- 20691710
TI  - Epigenomics of human colon cancer.
AB  - DNA methylation exerts critical effects on gene-expression regulation in normal
      cells, and alterations on the normal methylation patterns characterize, and
      likely contribute, to cancer development and progression. The complete
      understanding of the distinctiveness, role and dynamics of the cancer cell
      epigenome has been hindered so far by technical limitations, and new, whole
      genome approaches are required. Here we review the methods that have permitted us
      glimpses of the colon cancer methylome and outline future directions that will
      eventually lead researchers to identify the altered epigenetic patterns in cancer
      cells.

PMID- 20691711
TI  - An "Omics" based survey of human colon cancer.
AB  - Despite an increased understanding of the molecular pathogenesis of colorectal
      cancer (CRC) during the past two decades, reliable and robust biomarkers to
      enable screening, surveillance, and primary prevention of this disease are
      lacking. CRC diagnosis and therapy remain dependent upon descriptive
      classification and staging systems, based primarily on morphology and histology.
      The traditional approach of understanding complex biological systems by studying
      smaller, discrete units of the whole system has been less fruitful for
      understanding complex diseases. The implicit assumption of traditional methods,
      that a single or even only a few factors, play a dominant role in a complex
      disease might be inadequate when studying multifactorial diseases such as cancer.
      The burgeoning field of systems biology adopts a holistic approach, wherein the
      integration of individual parts of the system is sought. The cornerstone of a
      systems biology approach has been the development of a variety of high-throughput
      "omics" sciences, including genomics, transcriptomics, proteomics, and
      metabolomics. This review will focus on the "omics" literature in the field of
      sporadic human CRC and present examples of how a systems approach has been
      extremely useful in understanding concepts that would have been difficult to
      develop using traditional methods.

PMID- 20691712
TI  - Transcriptional characterization of Salmonella TA100 in log and stationary phase:
      influence of growth phase on mutagenicity of MX.
AB  - The Salmonella mutagenicity assay can be performed using cells that are in
      different growth phases. Thus, the plate-incorporation assay involves plating
      stationary-phase cells with the mutagen, after which the cells undergo a brief
      lag phase and, consequently, are exposed to the mutagen and undergo mutagenesis
      while in the logarithmic (log) phase. In contrast, a liquid-suspension assay
      involves exposure of either log- or stationary-phase cells to the mutagen for a
      specified period of time, sometimes followed by a wash, resulting in the cells
      growing in medium in the absence of the mutagen. To explore global gene
      expression in Salmonella, and to test for possible effects of growth phase and
      transcriptional status on mutagenesis, we performed microarray analysis on cells
      of Salmonella strain TA100 exposed to the drinking-water mutagen MX in either the
      log or stationary phase. The genes in functional pathways involving amino acid
      transport and metabolism and energy metabolism were expressed differentially in
      log-phase cells, whereas genes in functional pathways involving protein
      trafficking, cell envelope, and two-component systems using common signal
      transduction were expressed differentially in stationary-phase cells. More than
      90% of the ribosomal-protein biosynthesis genes were up-regulated in stationary-
      versus log-phase cells. MX was equally mutagenic to cells in log- and stationary
      phase growth when the results were expressed as mutant frequencies
      (revertants/survivors/MUM), but it was twice as mutagenic in stationary-phase
      cells when the results were expressed as mutant yields (revertants/nmole or
      revertants/MUM). There was a complex transcriptional response underlying these
      results, with mucA/B being greatly up-regulated in log-phase cells but umuC/D up
      regulated in stationary-phase cells. The transcriptional state of TA100 cells at
      the time of mutagen treatment may influence the outcome of mutagen treatment.

PMID- 20691713
TI  - Pharmacological characterisation of the GlyT-1 glycine transporter using two
      novel radioligands.
AB  - Inhibitors of the glycine transporter GlyT-1 are being developed as potential
      treatments for schizophrenia. Here we report on the use of two novel
      radioligands, [(3)H]-SB-733993 and [(3)H]-GSK931145, for the characterisation of
      GlyT-1 in both cells and native tissue. Binding was evaluated in membranes either
      from HEK293 cells expressing recombinant human GlyT-1 (hGlyT-1) or from rat
      cerebral cortex. Specific binding of both [(3)H]-SB-733993 and [(3)H]-GSK931145
      to hGlyT-1 HEK293 cell membranes and rat cerebral cortex membranes was saturable
      and comprised >90% of total binding. K(d) and B(max) values for the two
      radioligands were fairly similar, with K(d) values of 1-2 nM and B(max) values of
      around 7000 fmol/mg protein in hGlyT-1 membranes and 3000 fmol/mg protein in rat
      cortex membranes. Association of [(3)H]-SB-733993 was faster, with binding
      reaching equilibrium within 30 min compared with 90 min for [(3)H]-GSK931145.
      Dissociation was also much slower for [(3)H]-GSK931145 than for [(3)H]-SB-733993,
      with 50% of specific binding being dissociated by approximately 40 min and 5 min,
      respectively. Autoradiography studies with [(3)H]-GSK931145 showed widespread
      distribution of binding in rat brain, with generally higher binding in caudal
      compared with rostral areas. Initial studies in human frontal cortex membranes
      showed clear specific binding of [(3)H]-GSK931145, though with much lower density
      (B(max) 570 fmol/mg protein) and slightly lower affinity (K(d) 4.5 nM) compared
      with rat cortex. A human brain autoradiography study showed higher specific
      binding in cerebellum compared with frontal cortex. All GlyT-1 inhibitors tested,
      as well as glycine itself, competed fully for the binding of both [(3)H]-SB
      733993 and [(3)H]-GSK931145 in both hGlyT-1 and rat cortex membranes. Studies on
      the effect of varying NaCl concentration showed that [(3)H]-SB-733993 binding was
      reduced by >90% in the absence of added Na(+) ions, whilst [(3)H]-GSK931145
      binding was unaffected. Glycine produced concentration-dependent decreases in
      binding affinity of both radioligands without major changes in B(max) values,
      suggesting that both [(3)H]-SB-733993 and [(3)H]-GSK931145 bind to sites on GlyT
      1 that are orthosteric to the site at which glycine itself binds. Overall, these
      results show that both [(3)H]-SB-733993 and [(3)H]-GSK931145 are useful
      radioligands for studies on GlyT-1 in both cell lines and native tissues, with
      [(3)H]-GSK931145 being the radioligand of choice for further studies on GlyT-1
      expression and pharmacology.

PMID- 20691714
TI  - Oculomotor integration in patients with a pulvinar lesion.
AB  - The pulvinar nucleus of the thalamus, with its connections to visual areas and to
      frontal and parietal oculomotor cortex, might serve as a nexus for integrating
      cortical control of voluntary eye movements with reflexive eye movements
      generated by the superior colliculus. To investigate this hypothesis, we tested
      five patients with a unilateral lesion of the pulvinar on the oculomotor capture
      paradigm. In this task, participants have to ignore a distractor item and make a
      saccade to a target in a visual search display. Results showed that the
      interference of the distractor was stronger when it was presented contralateral
      to their lesion compared to when it was presented in the ipsilesional visual
      field. These findings were confirmed by an additional single case experiment in
      which we measured saccade trajectory deviations as evoked by a single distractor.
      These results show that the pulvinar is involved in the successful influence of
      higher order signals (like our goals and intentions) on the guidance of our eye
      movements.

PMID- 20691715
TI  - Slower eating rate is independent to gastric emptying in obese minipigs.
AB  - The aim of our study was to investigate whether the altered eating behavior
      observed in the context of a diet-induced metabolic syndrome is related to
      changes of the gastric emptying and autonomic balance. Eight adult male Gottingen
      minipigs were subjected during 5months to ad libitum Western diet (WD). Several
      factors were compared between the lean (before WD) and obese conditions: general
      activity and eating behavior, gastric emptying, adiposity, glycemia and
      insulinemia during IVGTT, and heart rate variability (HRV). In our model, obesity
      did not alter the gastric emptying (258+/-26 vs. 256+/-14 min, P>0.10) but
      induced insulin resistance: increased basal insulinemia (12.6+/-0.8 to 36.6+/-6.1
      mU/l, P<0.02) and reduced insulin sensitivity (4.5E-4+/-0.7E-4 to 2.5E-4+/-0.2E-4
      min(-1) per mU.l(-1) of insulin, P<0.05). The HRV and sympathovagal balance were
      not significantly modified (P>0.10). Fed ad libitum with WD, animals overate
      durably (P<0.001). During a 30-min meal test though, the ingestion speed, the
      food ingested (1076+/-48 vs. 520+/-52 g) and energy intake decreased in the obese
      condition (P<0.05), which can be explained by the fragmentation of the daily
      caloric intake. These data suggest that the slower eating rate and increased
      number of meals observed in obese minipigs without neuropathy is independent to
      gastric emptying. The explanation may be sought rather in central modifications
      induced by obesity that might modify the food perception and/or motivation.

PMID- 20691716
TI  - Interaction between organophosphate pesticide exposure and PON1 activity on
      thyroid function.
AB  - Organophosphate pesticides are widely used in agricultural purposes. Recently, a
      few studies have demonstrated the ability of these chemicals to alter the
      function of the thyroid gland in human. Moreover, the paraoxonase-1 enzyme (PON1)
      plays an important role in the toxicity of some organophosphate pesticides, with
      low PON1 activity being associated with higher pesticide sensitivity. This study
      evaluates the interaction between exposure to organophosphate compounds and PON1
      enzyme activity on serum levels of TSH and thyroid hormones in a population of
      workers occupationally exposed to pesticides. A longitudinal study was conducted
      on a population of floriculture workers from Mexico, during two periods of high
      and low-intensity levels of pesticide application. A structured questionnaire was
      completed by workers containing questions on sociodemographic characteristics and
      other variables of interest. Urine and blood samples were taken, and biomarkers
      of exposure (dialkylphosphates), susceptibility (PON1 polymorphisms and activity)
      and effect (thyroid hormone levels) were determined. Interaction between
      dialkylphosphates and PON1 polymorphisms or PON1 activity on hormone levels was
      evaluated by generalized estimating equation (GEE) models. A significant
      interaction was found between serum diazoxonase activity and total
      dialkylphosphates (SigmaDAP) on TSH levels. Thus, when PON1 activity was
      increased we observed a decrease in the percentage of variation of TSH level for
      each increment in one logarithmic unit of the SigmaDAP levels. This interaction
      was also observed with the PON1(192)RR genotype. These results suggest a stronger
      association between organophosphate pesticides and thyroid function in
      individuals with lower PON1 activity.

PMID- 20691717
TI  - NMR-based metabonomic analysis of the hepatotoxicity induced by combined exposure
      to PCBs and TCDD in rats.
AB  - A metabonomic approach using (1)H NMR spectroscopy was adopted to investigate the
      metabonomic pattern of rat urine after oral administration of environmental
      endocrine disruptors (EDs) polychlorinated biphenyls (PCBs) and 2,3,7,8
      tetrachlorodibenzo- p-dioxin (TCDD) alone or in combination and to explore the
      possible hepatotoxic mechanisms of combined exposure to PCBs and TCDD. (1)H NMR
      spectra of urines collected 24h before and after exposure were analyzed via
      pattern recognition by using principal component analysis (PCA). Serum
      biochemistry and liver histopathology indicated significant hepatotoxicity in the
      rats of the combined group. The PCA scores plots of urinary (1)H NMR data showed
      that all the treatment groups could be easily distinguished from the control
      group, so could the PCBs or TCDD group and the combined group. The loadings plots
      of the PCA revealed remarkable increases in the levels of lactate, glucose,
      taurine, creatine, and 2-hydroxy-isovaleric acid and reductions in the levels of
      2-oxoglutarate, citrate, succinate, hippurate, and trimethylamine-N-oxide in rat
      urine after exposure. These changes were more striking in the combined group. The
      changed metabolites may be considered possible biomarker for the hepatotoxicity.
      The present study demonstrates that combined exposure to PCBs and TCDD induced
      significant hepatotoxicity in rats, and mitochondrial dysfunction and fatty acid
      metabolism perturbations might contribute to the hepatotoxicity. There was good
      conformity between changes in the urine metabonomic pattern and those in serum
      biochemistry and liver histopathology. These results showed that the NMR-based
      metabonomic approach may provide a promising technique for the evaluation of the
      combined toxicity of EDs.

PMID- 20691718
TI  - Dose-related gene expression changes in forebrain following acute, low-level
      chlorpyrifos exposure in neonatal rats.
AB  - Chlorpyrifos (CPF) is a widely used organophosphorus insecticide (OP) and
      putative developmental neurotoxicant in humans. The acute toxicity of CPF is
      elicited by acetylcholinesterase (AChE) inhibition. We characterized dose-related
      (0.1, 0.5, 1 and 2mg/kg) gene expression profiles and changes in cell signaling
      pathways 24h following acute CPF exposure in 7-day-old rats. Microarray
      experiments indicated that approximately 9% of the 44,000 genes were
      differentially expressed following either one of the four CPF dosages studied
      (546, 505, 522, and 3,066 genes with 0.1, 0.5, 1.0 and 2.0mg/kg CPF). Genes were
      grouped according to dose-related expression patterns using K-means clustering
      while gene networks and canonical pathways were evaluated using Ingenuity Pathway
      Analysis(r). Twenty clusters were identified and differential expression of
      selected genes was verified by RT-PCR. The four largest clusters (each containing
      from 276 to 905 genes) constituted over 50% of all differentially expressed genes
      and exhibited up-regulation following exposure to the highest dosage (2mg/kg
      CPF). The total number of gene networks affected by CPF also rose sharply with
      the highest dosage of CPF (18, 16, 18 and 50 with 0.1, 0.5, 1 and 2mg/kg CPF).
      Forebrain cholinesterase (ChE) activity was significantly reduced (26%) only in
      the highest dosage group. Based on magnitude of dose-related changes in
      differentially expressed genes, relative numbers of gene clusters and signaling
      networks affected, and forebrain ChE inhibition only at 2mg/kg CPF, we focused
      subsequent analyses on this treatment group. Six canonical pathways were
      identified that were significantly affected by 2mg/kg CPF (MAPK, oxidative
      stress, NFKappaB, mitochondrial dysfunction, arylhydrocarbon receptor and
      adrenergic receptor signaling). Evaluation of different cellular functions of the
      differentially expressed genes suggested changes related to olfactory receptors,
      cell adhesion/migration, synapse/synaptic transmission and
      transcription/translation. Nine genes were differentially affected in all four
      CPF dosing groups. We conclude that the most robust, consistent changes in
      differential gene expression in neonatal forebrain across a range of acute CPF
      dosages occurred at an exposure level associated with the classical marker of OP
      toxicity, AChE inhibition. Disruption of multiple cellular pathways, in
      particular cell adhesion, may contribute to the developmental neurotoxicity
      potential of this pesticide.

PMID- 20691720
TI  - Oculomotor capture by colour singletons depends on intertrial priming.
AB  - In visual search, an irrelevant colour singleton captures attention when the
      colour of the distractor changes across trials (e.g., from red to green), but not
      when the colour remains constant (Becker, 2007). The present study shows that
      intertrial changes of the distractor colour also modulate oculomotor capture: an
      irrelevant colour singleton distractor was only selected more frequently than the
      inconspicuous nontargets (1) when its features had switched (compared to the
      previous trial), or (2) when the distractor had been presented at the same
      position as the target on the previous trial. These results throw doubt on the
      notion that colour distractors capture attention and the eyes because of their
      high feature contrast, which is available at an earlier point in time than
      information about specific feature values. Instead, attention and eye movements
      are apparently controlled by a system that operates on feature-specific
      information, and gauges the informativity of nominally irrelevant features.

PMID- 20691719
TI  - Hormetic effect of methylmercury on Caenorhabditis elegans.
AB  - Research has demonstrated the toxic effects of methylmercury (MeHg), yet
      molecular mechanisms underlying its toxicity are not completely understood.
      Caenorhabditis elegans (C. elegans) offers a unique biological model to explore
      mechanisms of MeHg toxicity given many advantages associated with its ease of use
      and genetic power. Since our previous work indicated neurotoxic resistance of C.
      elegans to MeHg, the present study was designed to examine molecular mechanisms
      associated with this resistance. We hypothesized MeHg would induce expression of
      gst, hsp or mtl in vivo since glutathione (GSH), heat shock proteins (HSPs), and
      metallothioneins (MTs) have shown involvement in MeHg toxicity. Our studies
      demonstrated a modest, but significant increase in fluorescence in gst-4::GFP and
      mtl-1::GFP strains at an acute, low L1 MeHg exposure, whereas chronic L4 MeHg
      exposure induced expression of gst-4::GFP and hsp-4::GFP. Knockout gst-4 animals
      showed no alterations in lethality sensitivity compared to wildtype animals
      whereas mtl knockouts displayed increased sensitivity to MeHg exposure. GSH
      levels were increased by acute MeHg treatment and depleted with chronic exposure.
      We also demonstrate that MeHg induces hormesis, a phenotype whereby a sublethal
      exposure to MeHg rendered C. elegans resistant to subsequent exposure to the
      organometal. The involvement of gst-4, hsp-4, mtl-1, and mtl-2 in hormesis was
      examined. An increase in gst-4::GFP expression after a low-dose acute exposure to
      MeHg indicated that gst-4 may be involved in this response. Our results implicate
      GSH, HSPs, and MTs in protecting C. elegans from MeHg toxicity and show a
      potential role of gst-4 in MeHg-induced hormesis.

PMID- 20691721
TI  - A prospective study of leisure-time physical activity and mental health in
      Swedish health care workers and social insurance officers.
AB  - OBJECTIVE: This study analyzes longitudinal associations between self-reported
      leisure-time physical activity (PA) and perceived stress, burnout and symptoms of
      depression and anxiety. METHOD: Cohort data collected in 2004 and 2006 from
      health care and social insurance workers in western Sweden (2694 women; 420 men)
      were analyzed. Cox regression was conducted to examine associations between
      baseline levels of PA and mental health (MH) problems 2 years later. RESULTS:
      Cross-sectional analysis show that individuals reporting either light physical
      activity (LPA) or moderate-to-vigorous physical activity (MVPA) were less likely
      to report high levels of perceived stress, burnout and symptoms of depression and
      anxiety, as compared to individuals reporting a sedentary lifestyle. The risks of
      symptoms of depression, burnout, and high stress levels at follow-up were
      significantly lower for those reporting LPA or MVPA at baseline. For symptoms of
      anxiety, an activity level corresponding to MVPA was required. CONCLUSION:
      Participation in PA appeared to lower the risk of developing MH problems two
      years later. This relationship involved LPA and MVPA regarding feelings of
      depression, burnout and perceived stress, and exclusively MVPA regarding feelings
      of anxiety. The implications of these findings are important, as preventive
      strategies for psychosocial stress and mental health problems are needed.

PMID- 20691722
TI  - Health screening services--ready for a "virtual" joyride?

PMID- 20691723
TI  - Extraction, chemical analysis of Angelica sinensis polysaccharides and
      antioxidant activity of the polysaccharides in ischemia-reperfusion rats.
AB  - Angelica sinensis polysaccharides were analyzed using high performance liquid
      chromatography (HPLC) and Fourier Transform Infrared (FT-IR). The major sugar of
      the polysaccharide was saccharose (18.55%); and the sugar constituted about 83%
      of the monomer content. Glucose and fructose were found as minor components of
      the polysaccharides. The FT-IR spectra of A. sinensis polysaccharides are used
      for determination of their structural features. The FT-IR spectrum of A. sinensis
      polysaccharides showed bands at 1641 cm(-1), 1415 cm(-1), 1050 cm(-1) and 926 cm(
      1) characteristic for the carboxylic group. Absorptions at 2920-2930 cm(-1) are
      attributed to asymmetrical stretching vibration of CH(2)-group. Medium stretch
      observed in the range 1650-1400 cm(-1) is assigned to C-C stretching of
      polysaccharides. Cardioprotective effects of A. sinensis polysaccharides were
      evaluated by using myocardial ischemia/reperfusion (IR) rats. A. sinensis
      polysaccharides treatment significantly reduced myocardial infarction size,
      enhanced CT-1 and antioxidant enzymes activity, downregulated caspase-12 mRNA
      expression in rats. The study strongly suggests the cardioprotective activity of
      A. sinensis polysaccharides in limiting ischemia-reperfusion induced myocardial
      injury.

PMID- 20691724
TI  - Trehalose protects urea-induced unfolding of alpha-chymotrypsin.
AB  - Trehalose, a naturally occurring osmolyte, appears to be one of the most
      effective protectants for enzymes under various stress conditions while urea, a
      classical denaturant, destabilizes the activity, function, and alters the native
      structure of proteins. Herein, we have characterized the counteracting effects of
      trehalose on the deleterious effect of urea on alpha-chymotrypsin (CT) through
      the calorimetric data (transition temperature (T(m)), enthalpy change (DeltaH),
      heat capacity change (DeltaC(p)) and Gibbs free energy of unfolding (DeltaG(u))
      by using differential scanning calorimeter (DSC) and circular dichroism (CD)
      techniques, respectively, at a 1:2 ratio of trehalose and urea, as well as
      various urea concentration (up to 6 M) in the presence of 1 M trehalose. Our
      parallel experimental results explicitly elucidate that trehalose strongly offset
      the deleterious actions of urea on CT at 1:2 molar ratio of trehalose and urea,
      however, trehalose (1 M) some how failed to counteract the perturbation effects
      of urea (3-6 M) on CT.

PMID- 20691726
TI  - Apropos "Seroprevalence of common vaccine-preventable viral infections in HIV
      positive adults".

PMID- 20691727
TI  - A new rodent behavioral paradigm for studying forelimb movement.
AB  - The center-out task is a standard paradigm often used to study the neural control
      of reaching movements in human and non-human primates. However, there are several
      disadvantages to the use of monkeys, notably costs, infrastructural requirements,
      and ethical considerations. Here we describe a similar task designed to examine
      forelimb movements in rats. Rats were trained to grasp a joystick with their
      forepaw and use it to control the movements of a sipper tube in two dimensions.
      The rats learned to move the joystick in four directions with at least 70%
      accuracy after about 45 days of training. In addition, rats were able to learn a
      reversed mapping between joystick and sipper tube movement. This is a more
      complicated behavior than has been previously demonstrated for rats, and it could
      allow more motor behavior studies to be conducted in rodents instead of monkeys.
      We currently are using this behavior to decode the rats' forelimb movements from
      their brain signals.

PMID- 20691728
TI  - Recordings from human myenteric neurons using voltage-sensitive dyes.
AB  - Voltage-sensitive dye (VSD) imaging became a powerful tool to detect neural
      activity in the enteric nervous system, including its routine use in submucous
      neurons in freshly dissected human tissue. However, VSD imaging of human
      myenteric neurons remained a challenge because of limited visibility of the
      ganglia and dye accessibility. We describe a protocol to apply VSD for recordings
      of human myenteric neurons in freshly dissected tissue and myenteric neurons in
      primary cultures. VSD imaging of guinea-pig myenteric neurons was used for
      reference. Electrical stimulation of interganglionic fiber tracts and exogenous
      application of nicotine or elevated KCl solution was used to evoke action
      potentials. Bath application of the VSDs Annine-6Plus, Di-4-ANEPPS, Di-8-ANEPPQ,
      Di-4-ANEPPDHQ or Di-8-ANEPPS revealed no neural signals in human tissue although
      most of these VSD worked in guinea-pig tissue. Unlike methylene blue and FM1-43,
      4-Di-2-ASP did not influence spike discharge and was used in human tissue to
      visualize myenteric ganglia as a prerequisite for targeted intraganglionic VSD
      application. Of all VSDs, only intraganglionic injection of Di-8-ANEPPS by a
      volume controlled injector revealed neuronal signals in human tissue. Signal-to
      noise ratio increased by addition of dipicrylamine to Di-8-ANEPPS (0.98+/-0.16
      vs. 2.4+/-0.62). Establishing VSD imaging in primary cultures of human myenteric
      neurons led to a further improvement of signal-to-noise ratio. This allowed us to
      routinely record spike discharge after nicotine application. The described
      protocol enabled reliable VSD recordings from human myenteric neurons but may
      also be relevant for the use of other fluorescent dyes in human tissues.

PMID- 20691725
TI  - The influences of environmental enrichment, cognitive enhancement, and physical
      exercise on brain development: can we alter the developmental trajectory of ADHD?
AB  - Attention-deficit/Hyperactivity Disorder (ADHD) is characterized by a pervasive
      pattern of developmentally inappropriate inattentive, impulsive and hyperactive
      behaviors that typically begin during the preschool years and often persist into
      adulthood. The most effective and widely used treatments for ADHD are medication
      and behavior modification. These empirically-supported interventions are
      generally successful in reducing ADHD symptoms, but treatment effects are rarely
      maintained beyond the active intervention. Because ADHD is now generally thought
      of as a chronic disorder that is often present well into adolescence and early
      adulthood, the need for continued treatment throughout the lifetime is both
      costly and problematic for a number of logistical reasons. Therefore, it would be
      highly beneficial if treatments would have lasting effects that remain after the
      intervention is terminated. This review examines the burgeoning literature on the
      underlying neural determinants of ADHD along with research demonstrating powerful
      influences of environmental factors on brain development and functioning. Based
      upon these largely distinct scientific literatures, we propose an approach that
      employs directed play and physical exercise to promote brain growth which, in
      turn, could lead to the development of potentially more enduring treatments for
      the disorder.

PMID- 20691729
TI  - Staining of fluorogold-prelabeled retinal ganglion cells with calcein-AM: A new
      method for assessing cell vitality.
AB  - PURPOSE: The number of retinal ganglion cells (RGC) is often used as an outcome
      measure in neuroprotection. The gold standard for staining RGC is retrograde
      labeling, e.g. with fluorogold (FG). However, this method alone does not permit
      to differentiate between viable and dead cells, because dying cells only avoid
      being counted once they have undergone complete microglial-phagocytosis. To
      differentiate between viable and dead but still existent RGC, we additionally
      stained FG-labeled RGC with calcein-acetoxymethylester (CAM). METHODS: The left
      optic nerves of rats were crushed 6 days after stereotactical injection of FG
      into both superior colliculi. The right eyes served as controls. Retinal whole
      mounts were prepared 2, 5, 8 or 11 days after optic nerve crush (ONC), and
      incubated for 30min in culture media containing 0.01% CAM. RGC densities were
      determined in defined areas at different eccentricities under a fluorescence
      microscope using the appropriate filters. Twice-positive RGC were counted after
      merging both filters. RESULTS: The loss of RGC induced by ONC is identified
      earlier when these cells are detected by FG+CAM rather than by FG-labeling alone.
      The percentages of FG-positive RGC stained with CAM were 83% in controls, 68% on
      day 2, 48% on day 5, 26% on day 8, and 9% on day 11 after ONC. The decay rate of
      FG-prelabeled RGC appears accelerated and becomes more linear when only viable
      RGC positive for CAM are counted. CONCLUSIONS: The staining of FG-prelabeled RGC
      with CAM permits the discrimination between dead and viable RGC in retinal whole
      mounts, which enables to quantify RGC degeneration earlier after injury than by
      using microglial-phagocytosis-dependant retrograde labeling alone.

PMID- 20691730
TI  - Nonspecific CXCR7 antibodies.

PMID- 20691731
TI  - Defining the immunoreactive epitope for the monoclonal anti-human glutathione
      peroxidase-4 antibody anti-hGPx4 Mab63-1.
AB  - Glutathione peroxidases (GPx) form a heterogeneous enzyme family and GPx4
      isoforms have been implicated in anti-oxidative defense, brain development,
      neuroinjury and sperm maturation. In humans seven GPx isoforms (GPx1-GPx7) can be
      separated. To selectively quantify the expression of GPx4-isoforms we have raised
      a monoclonal antibody (anti-hGPx4 Mab63-1) against the pure recombinant Sec46Cys
      mutant of human cytosolic GPx4 and used it for immunoblotting,
      immunoprecipitation and immunohistochemistry. The antibody recognizes human GPx4,
      its mouse ortholog but neither reacted with rat GPx4 nor other human GPx
      isoforms. Sequence alignment of human and rat GPx4 proteins indicated three
      different amino acids (S18, F35, K99 in humans, A18, C35, R99 in rats) and a S18A
      exchange in the human enzyme completely abolished immunoreactivity. To further
      characterize the immunological epitope we synthesized a set of 12-mer peptides
      flanking S18* of human GPx4 and found that the sequence SMHEFS*AKDIDG exhibited
      strongest immunoreactivity. Substitution analysis and peptide length variation
      narrowed down the essential epitope to FS*AKDI and indicated that most mutations
      in this region strongly impaired immunoreactivity. In silico blast searches of
      public protein databases failed to identify proteins with potential
      immunoreactivity suggesting that the antibody exhibits a high specificity for
      human and mouse GPx4 and may not cross-react with unrelated proteins.

PMID- 20691732
TI  - Assessment of bluetongue viraemia in sheep by real-time PCR and correlation with
      viral infectivity.
AB  - Inoculation of embryonated chicken eggs is the standard method for the titration
      of infectious Bluetongue virus (BTV). Here, six RNA extraction methods coupled
      with optimised dsRNA denaturation and real-time RT-PCR were evaluated for the
      quantitation of BTV in blood samples from experimentally infected sheep and
      results were correlated to infectious virus titres. An exogenous dsRNA internal
      control (IC) from the closely related Epizootic hemorrhagic disease virus (EHDV)
      was used to assess the efficiency of BTV genome extraction, dsRNA denaturation,
      RT, and PCR amplification. Recovery rates of IC and BTV dsRNA copies from
      extracted blood samples were highly correlated. Adjustment of BTV concentrations
      according to the IC recovery reduced variation in sample analyses among the
      different extraction methods and improved the accuracy of BTV quantitation. The
      EID(50)/ml titre, determined in blood samples from sheep infected experimentally
      with BTV-1 or BTV-9, correlated highly with the assessed concentration of BTV
      dsRNA copies. However, this correlation was consistent only during the first 28
      days post-infection. The optimised extraction methods and quantitative RT-PCR
      could be useful for experimental studies of BTV transmission, pathogenesis and
      vaccine efficacy, or adapted further for the detection and quantitation of EHDV,
      African horse sickness virus and other dsRNA viruses.

PMID- 20691733
TI  - Cucumber mosaic virus as the expression system for a potential vaccine against
      Alzheimer's disease.
AB  - A primary therapeutic goal in Alzheimer's disease (AD) is to reduce the quantity
      of amyloid beta protein (Abeta) present in the brain. To develop an effective,
      safe system for vaccination against Alzheimer's disease, the plant virus Cucumber
      mosaic virus (CMV) was engineered genetically to express Abeta-derived fragments
      that stimulate mainly humoral immune responses. Six chimeric constructs, bearing
      the Abeta1-15 or the Abeta4-15 sequence in positions 248, 392 or 529 of the CMV
      coat protein (CP) gene, were created. Viral products proved to be able to
      replicate in their natural host. However, only chimeric Abeta1-15-CMVs were
      detected by Abeta1-42 antiserum in Western blot analysis. Experimental evidence
      of Immunoelectron microscopy revealed a complete decoration of Abeta1-15-CMV(248)
      and Abeta1-15-CMV(392) following incubation with either anti-Abeta1-15 or anti
      Abeta1-42 polyclonal antibodies. These two chimeric CMVs appear to be endowed
      with features making them possible candidates for vaccination against Alzheimer's
      disease.

PMID- 20691734
TI  - Enhanced specificity of real-time PCR for measurement of hepatitis B virus cccDNA
      using restriction endonuclease and plasmid-safe ATP-dependent DNase and selective
      primers.
AB  - The persistence of covalently closed circular DNA (cccDNA) of hepatitis B virus
      (HBV) in hepatocytes plays a key role in viral persistence and resistance to
      therapy. Therefore, quantitative cccDNA measurement is of clinical importance for
      evaluating the efficacy of antiviral drugs, selecting an appropriate treatment
      strategy, and predicting the prognosis. Current established methods for
      measurement of cccDNA need further improvement. A modified method was developed
      using digestion with restriction endonucleases that do not recognize sites in the
      HBV DNA and plasmid-safe ATP-dependent DNase (PSAD), and using a cccDNA-specific
      primer set in a real-time PCR reaction. The cccDNA-specific primer has a similar
      amplification efficiency as a commercial kit. Treatment of samples with
      restriction endonuclease followed by PSAD digestion increased significantly the
      specificity of a cccDNA-selective primer set compared with other treatments
      (P<0.05). Analysis of 35 serum and liver DNA samples from patients with
      hepatocellular carcinoma demonstrated that the amount of serum cccDNA is beyond
      the minimum detection limit and that the liver cccDNA quantity is about 0-49.2
      copies/cell, consistent with previous reports. Taken together, this method has
      the potential for evaluating the efficacy of antiviral drugs.

PMID- 20691735
TI  - Comparison of two commercial molecular assays for simultaneous detection of
      respiratory viruses in clinical samples using two automatic electrophoresis
      detection systems.
AB  - Two molecular assays were compared with real-time RT-PCR and viral culture for
      simultaneous detection of common viruses from respiratory samples: a multiplex
      ligation-dependant probe amplification (MLPA) and a dual priming oligonucleotide
      system (DPO). In addition, the positive detections of MLPA and DPO were
      identified using two different automatic electrophoresis systems. A panel of 168
      culture-positive and negative samples was tested by the molecular assays for the
      presence of influenza A and B virus, respiratory syncytial virus, human
      metapneumovirus, rhinovirus, coronaviruses, parainfluenza viruses and adenovirus.
      One hundred and twenty-nine (77%) samples were positive as detected by at least
      one method. Sixty-nine (41%) samples were positive by cell culture (excluding
      human metapneumovirus and coronaviruses), 116 (69%) by RT-PCR, 127 (76%) by MLPA
      and 100 (60%) by DPO. The MLPA yielded results in one attempt for all samples
      included while 12 (7.2%) samples had to be repeated by the DPO assay due to
      inconclusive results. The MLPA assay performed well in combination with either
      electrophoresis system, while the performance of the DPO assay was influenced by
      the electrophoresis systems. Both molecular assays are comparable with real-time
      RT-PCR, more sensitive than viral culture and can detect dual infections easily.
      Results can be obtained within 1 day.

PMID- 20691736
TI  - Expression, purification and immunogenic characterization of hepatitis C virus
      recombinant E1E2 protein expressed by Pichia pastoris yeast.
AB  - Development of an effective vaccine may be the key in the control of hepatitis C
      virus (HCV) infection. Recent studies have shown that HCV envelope proteins can
      induce broadly neutralizing antibodies against conserved domain for HCV binding
      to the cellular receptors. So HCV envelope proteins are considered as the major
      HCV vaccine candidate. In this study, we used Pichia pastoris yeast to express
      truncated HCV E1E2 protein, which consists of E1 residues 187-346 and E2 residues
      381-699. The yeast can produce high level of recombinant HCV E1E2 protein. The
      protein has complex glycosylation and can bind to CD81, the putative HCV
      receptor. Moreover, the purified protein can efficiently induce anti-E1E2
      antibodies in rabbits, which are able to neutralize two kinds of HCV pseudotype
      particles derived from HCV genotype 1a and 1b, as well as HCV virions derived
      from HCV genotype 2a. These findings indicate that the recombinant E1E2
      glycoprotein is effective in inducing broadly neutralizing antibodies, and is a
      potent HCV vaccine candidate.

PMID- 20691737
TI  - Lifelong persistent EBV infection of rabbits with EBER1-positive lymphocyte
      infiltration and mild sublethal hemophagocytosis.
AB  - Most humans become lifelong carriers of Epstein-Barr virus (EBV) by adulthood.
      Primary EBV infection in adolescents causes in one to two-third of cases
      infectious mononucleosis. EBV infection is associated with various diseases,
      neoplasms and hematological disorders. Recently we reported that EBV can infect
      rabbits frequently by intravenous, intranasal or/and peroral inoculation, which
      caused primary EBV infection in rabbits with heterogeneous host reactions. Here
      we presented follow up data that of six primary EBV-infected rabbits out of seven
      inoculated intravenously with EBV, two out of six EBV-infected rabbits showed
      lifetime EBV infection. (1) EBV-DNA were detected in blood through life. (2) High
      antibody titers against EA-D were maintained over 1000 days. (3) A focal mass
      lesion was transiently observed by ultrasonography in the spleen of one rabbit.
      (4) Two lifelong EBV-detected rabbits died on day 1522 or 1400, and autopsy
      revealed proliferation of lymphocytes expressing EBER1 or LMP1 accompanied with
      mild hemophagocytosis in the spleen or lymph nodes. We hypothesized some EBV
      infected rabbits could not eliminate EBV for life and showed somewhat similar
      features to persistent EBV infection, mild CAEBV and/or mild sublethal
      hemophagocytosis. These lifelong EBV-infected rabbits might be a new useful
      animal model for studying lifelong persistent EBV infection, taking place in
      almost all adults.

PMID- 20691738
TI  - Drug delivery system based on chronobiology--A review.
AB  - With the advancement in the field of chronobiology, modern drug delivery
      approaches have been elevated to a new concept of chronopharmacology i.e. the
      ability to deliver the therapeutic agent to a patient in a staggered profile.
      However the major drawback in the development of such delivery system that
      matches the circadian rhythm requires the availability of precise technology
      (pulsatile drug delivery). The increasing research interest surrounding this
      delivery system has widened the areas of pharmaceutics in particular with many
      more sub-disciplines expected to coexist in the near future. This review on
      chronopharmaceutics gives a comprehensive emphasis on potential disease targets,
      revisits the existing technologies in hand and also addresses the theoretical
      approaches to emerging discipline such as genetic engineering and target based
      specific molecules. With the biological prospective approaches in delivering
      drugs it is well understood that safer and more realistic approaches in the
      therapy of diseases will be achieved in the days to come.

PMID- 20691739
TI  - Polymersomes of asymmetric bilayer membrane formed by phase-guided assembly.
AB  - Encapsulating delicate biomolecules into submicron-sized polymer particulate
      systems with preserved native conformation and sufficient loading efficiency is
      of great challenge. To address this issue, we developed a unique polymersome
      which differs from reported polymersome in that its bilayer membrane was formed
      of two different amphiphilic diblock copolymers in an "asymmetric" way. By adding
      two diblock copolymers, poly (ethylene glycol)-block-poly (epsilon-caprolactone)
      (PEG-PCL) and dextran-block-poly (epsilon-caprolactone) (DEX-PCL), into a so
      called dextran-in-PEG aqueous two-phase system, DEX-PCL formed the inner leaflet
      around the dispersed dextran phase and PEG-PCL formed the outer leaflet with the
      PEG block facing the PEG continuous phase. We name this unique assembly process
      as "phase-guided assembly". Polymersomes of asymmetric bilayer membrane possess a
      series of advantages over "symmetric" polymer bilayer vesicles previously
      reported. The asymmetric bilayer created a different chemical environment of the
      interior to which proteins were encapsulated highly efficiently (up to 90%) by
      thermodynamically favored partition. Probably due to the thermodynamic
      preference, erythropoietin (EPO) encapsulated in this system showed a well
      preserved bioactivity in cell proliferation assay. The core of the polymersomes
      may be cross-linked to enhance their mechanical strength. Phase-guided assembly
      system and asymmetric bilayer polymersomes demonstrated in this study may serve
      the high demands for delivering nucleotide and protein medicines and other
      biological applications.

PMID- 20691740
TI  - Transmembrane diffusion of gemcitabine by a nanoparticulate squalenoyl prodrug:
      an original drug delivery pathway.
AB  - We have designed an amphiphilic prodrug of gemcitabine (dFdC) by its covalent
      coupling to a derivative of squalene, a natural lipid. The resulting bioconjugate
      self-assembled spontaneously in water as nanoparticles that displayed a promising
      in vivo anticancer activity. The aim of the present study was to provide further
      insight into the in vitro subcellular localization and on the metabolization
      pathway of the prodrug. Cells treated with radiolabelled squalenoyl gemcitabine
      (SQdFdC) were studied by differential detergent permeation, and microautography
      coupled to fluorescent immunolabeling and confocal microscopy. This revealed that
      the bioconjugate accumulated within cellular membranes, especially in those of
      the endoplasmic reticulum. Radio-chromatography analysis proved that SQdFdC
      delivered dFdC directly in the cell cytoplasm. Mass spectrometry studies
      confirmed that gemcitabine was then either converted into its biologically active
      triphosphate metabolite or exported from the cells through membrane transporters.
      To our knowledge, this is the first description of such an intracellular drug
      delivery pathway. In vitro cytotoxicity assays revealed that SQdFdC was more
      active than dFdC on a transporter-deficient human resistant leukemia model, which
      was explained by the subcellular distribution of the drugs and their metabolites.
      The squalenoylation drug delivery strategy might, therefore, dramatically improve
      the efficacy of gemcitabine on transporter-deficient resistant cancer in the
      clinical context.

PMID- 20691741
TI  - Polymer particle shape independently influences binding and internalization by
      macrophages.
AB  - The interaction of macrophages with micro and nanoparticles (MNPs) is important
      because these cells clear particles from the circulation, and because they are
      potential therapeutic targets in inflammatory conditions, atherosclerosis and
      cancer. Therefore, an understanding of the features of MNPs that influence their
      interaction with macrophages may allow optimization of their properties for
      enhanced drug delivery. In this study, we show that particle shape impacts
      phagocytosis by macrophages, and more importantly, that particle shape and size
      separately impact attachment and internalization. The study provides a
      methodology for further exploring how particle shape can be controlled to achieve
      desired attachment and internalization. The results of the study also give
      mechanistic guidance on how particle shape can be manipulated to design drug
      carriers to evade macrophages, or alternatively to target macrophages.

PMID- 20691742
TI  - Central orexin-A increases gastric motility in rats.
AB  - Orexin receptor type-1 (OX1R) is expressed in the dorsal motor nucleus of vagi
      (DMV). Although orexin-A (OXA) plays an important role in mediating stress
      responses, it remains unclear how central OXA regulates gastric dysmotility
      induced by stress. Acute restraint stress (ARS) delays solid gastric emptying via
      the central corticotropin releasing factor (CRF) and peripheral autonomic neural
      pathways. We have previously shown that ARS impairs postprandial antro-pyloric
      coordination and delays solid gastric emptying in rats. We also showed that
      postprandial gastric contractions were augmented in response to ARS in rats.
      However, the mechanism of augmented postprandial gastric contractions induced by
      ARS remains unclear. We tested the hypothesis that augmented gastric motility
      induced by ARS is mediated via the central OX1R. We also assessed the role of
      endogenous OXA in the mediation of gastric motility under non-stressed conditions
      in conscious rats. A strain gauge transducer was implanted on the antrum to
      record postprandial gastric motility. To investigate whether endogenous OXA is
      involved in ARS-induced augmented gastric motility, selective OX1R antagonist, SB
      334867 (16 MUg), was administered intracerebroventricularly (icv). Icv-injection
      of SB-334867 abolished the augmented gastric contractions induced by ARS.
      Spontaneous postprandial gastric motility was enhanced by icv-injection of OXA
      (10 MUg), while it was attenuated by icv-injection of SB-3334867. It is suggested
      that central OXA mediates augmented gastric motility induced by ARS in rats.
      Central OXA also modulates postprandial gastric contractions in non-stressed
      conditions.

PMID- 20691743
TI  - Nuclear localization of vasoactive intestinal peptide (VIP) receptors in human
      breast cancer.
AB  - Vasoactive intestinal peptide (VIP) and its receptors (VPACs) are involved in
      proliferation, survival, and differentiation in human breast cancer cells. Its
      mechanism of action is traditionally thought to be through specific plasma
      membrane receptors. There is compelling evidence for a novel intracrine mode of
      genomic regulation by G-protein-coupled receptors (GPCRs) that implies both
      endocytosis and nuclear translocation of peripheral GPCR and/or the activation of
      nuclear-located GPCRs by endogenously-produced, non-secreted ligands. Regarding
      to VPAC receptors, which are GPCRs, there is only a report suggesting them as a
      dynamic system for signaling from plasma membrane and nuclear membrane complex.
      In this study, we show that VPAC(1) receptor is localized in cell nuclear
      fraction whereas VPAC(2) receptor presents an extranuclear localization and its
      protein expression is lower than that of VPAC(1) receptor in human breast tissue
      samples. Both receptors as well as VIP are overexpressed in breast cancer as
      compared to non-tumor tissue. Moreover, we report the markedly nuclear
      localization of VPAC(1) receptors in estrogen-dependent (T47D) and independent
      (MDA-MB-468) human breast cancer cell lines. VPAC(1) receptors are functional in
      plasma membrane and nucleus as shown by VIP stimulation of cAMP production in
      both cell lines. In addition, VIP increases its own intracellular and
      extracellular levels, and could be involved in the regulation of VPAC(1)-receptor
      traffic from the plasma membrane to the nucleus. These results support new
      concepts on function and regulation of nuclear GPCRs which could have an impact
      on development of new therapeutic drugs.

PMID- 20691744
TI  - Beyond the serotonin hypothesis: mitochondria, inflammation and neurodegeneration
      in major depression and affective spectrum disorders.
AB  - For many years, a deficiency of monoamines including serotonin has been the
      prevailing hypothesis on depression, yet research has failed to confirm
      consistent relations between brain serotonin and depression. High degrees of
      overlapping comorbidities and common drug efficacies suggest that depression is
      one of a family of related conditions sometimes referred to as the "affective
      spectrum disorders", and variably including migraine, irritable bowel syndrome,
      chronic fatigue syndrome, fibromyalgia and generalized anxiety disorder, among
      many others. Herein, we present data from many different experimental modalities
      that strongly suggest components of mitochondrial dysfunction and inflammation in
      the pathogenesis of depression and other affective spectrum disorders. The three
      concepts of monoamines, energy metabolism and inflammatory pathways are inter
      related in many complex manners. For example, the major categories of drugs used
      to treat depression have been demonstrated to exert effects on mitochondria and
      inflammation, as well as on monoamines. Furthermore, commonly-used mitochondrial
      targeted treatments exert effects on mitochondria and inflammation, and are
      increasingly being shown to demonstrate efficacy in the affective spectrum
      disorders. We propose that interactions among monoamines, mitochondrial
      dysfunction and inflammation can inspire explanatory, rather than mere
      descriptive, models of these disorders.

PMID- 20691745
TI  - Doubtful association of antipsychotic polypharmacy and high dosage with cognition
      in chronic schizophrenia.
AB  - Despite consistent recommendations for antipsychotic monotherapy, antipsychotic
      polypharmacy (the use of two or more antipsychotic agents) and the administration
      of excessive doses (higher than 1000 mgr/day of chloropromazine equivalents) is a
      common practice in schizophrenia. The therapeutic and adverse effects of this
      practice are poorly studied, in particular with regards to the cognitive symptoms
      of the disease. In this cross-sectional study we investigated the cognitive
      effects of antipsychotic polypharmacy and excessive doses in 53 patients with
      chronic schizophrenia using non-verbal cognitive tasks involving speed of
      movement, memory and executive functions. No significant difference in
      performance scores was found between the groups under polypharmacy and
      monotherapy, or the groups receiving either excessive or normal doses of
      antipsychotics. Since these groups did not also differ in demographic, clinical,
      other pharmacologic parameters, in the relative anticholinergic potency of
      antipsychotics, or in intelligence scores, we raise doubts about the association
      of polypharmacy and excessive doses with non-verbal cognitive performance in
      chronic schizophrenia.

PMID- 20691746
TI  - Circadian rhythms and treatment implications in depression.
AB  - In humans almost all physiological and behavioural functions occur on a rhythmic
      basis. Therefore the possibility that delays, advances or desynchronizations of
      circadian rhythms may play a role in the pathophysiology of psychiatric disorders
      is an interesting field of research. In particular mood disorders such as
      seasonal affective disorder and major depression have been linked to circadian
      rhythms alterations. Furthermore, the antidepressant efficacy of both
      pharmacological and non-pharmacological strategies affecting endogenous circadian
      rhythms, such as new antidepressant medications, light-therapy and sleep
      deprivation, is consistent with the idea that circadian alterations may represent
      a core component of depression, at least in a subgroup of depressed patients.
      This paper briefly describes the molecular and genetic mechanisms regulating the
      endogenous clock system, and reviews the literature supporting the relationships
      between depression, antidepressant treatments and changes in circadian rhythms.

PMID- 20691747
TI  - Postoperative cognitive deficits and neuroinflammation in the hippocampus
      triggered by surgical trauma are exacerbated in aged rats.
AB  - Postoperative cognitive dysfunction (POCD) is characterized by the progressive
      deterioration of intellectual/cognitive function following surgery. It has been
      suggested that the senile brain, which characteristically expresses higher levels
      of central proinflammatory cytokines, interleukin (IL)-6, IL-1beta, and tumor
      necrosis factor (TNF)-alpha, is more susceptible to additional insult following
      surgery. The authors of this study investigated the expression of central
      cytokines IL-1beta, IL-6 and TNF-alpha and hippocampal glial cell activation in
      aged and adult rats following partial hepatectomy. Cognitive function was
      assessed in a reversal-learning version of the Morris water maze (MWM) before and
      after surgery. Hippocampal pro-inflammatory cytokines IL-1beta, IL-6 and TNF
      alpha and glial cell activation markers glial fibrillary acidic protein (GFAP)
      and S100beta were measured at each time point; CD200 and CD200R were also
      measured to explore potential mechanisms of glial cell activation. Surgical
      trauma resulted in impairments in distance and latency only on postoperative day
      1 (p<0.001, respectively) in adult rats. Aged rats exhibited impairments on day 1
      (p<0.001) that persisted until postoperative day 3 (p=0.002 and p=0.001,
      respectively). All significant impairments paralleled upregulated cytokine IL
      1beta and IL-6 expression. Immunohistochemistry assay further showed more
      hippocampal glial cell activation in aged rats compared to that in adults.
      Overall, these findings suggest that surgical trauma, rather than anesthesia,
      resulted in cognitive function impairment potentiated by aging. Hippocampal pro
      inflammatory cytokines and glial cell activation might mediate trauma-induced
      POCD.

PMID- 20691749
TI  - Antioxidant and hepatoprotective activities of five eggplant varieties.
AB  - Eggplant is consumed throughout the world and varies in fruit color, shape, and
      size. In this study, five varieties of eggplant (purple colored moderate size,
      white-green colored moderate size, long green, green striped moderate size and
      pale-green colored small size, respectively, called SM1-SM5) were evaluated for
      total phenolic and flavonoid content, antioxidant activity and hepatoprotection
      against cytotoxicity of tert-butyl hydroperoxide (t-BuOOH) in human hepatoma cell
      lines, HepG2. Total phenolic content found in methanol extracts of SM1-SM5 ranged
      from 739.36 +/- 1.59 to 1116.13 +/- 7.30 gallic acid equivalents mg/100g extract
      and total flavonoid content from 1991.29 +/- 6.32 to 3954.20 +/- 6.06 catechin
      equivalents mg/100 g extract. SM1 and SM2 which contained high total phenolic and
      flavonoid had better antioxidant activities than the other varieties.
      Pretreatment of HepG2 cells with 50 and 100 MUg/mL of SM1-SM5 significantly
      increased the viability (p<0.05) of t-BuOOH-exposed HepG2 cells by 14.49 +/-
      1.14% to 44.95 +/- 2.72%. The antioxidant activities of the eggplant were
      correlated with the total amounts of phenolic and flavonoid (r = 0.5310-0.7961).
      Significant correlation was found between hepatoprotective activities and total
      phenolic/flavonoid content (r = 0.6371-0.8842) and antioxidant activities (r =
      0.5846-0.9588), indicating the contribution of the phenolic antioxidant present
      in eggplant to its hepatoprotective effect on t-BuOOH-induced toxicity.

PMID- 20691748
TI  - Cyclooxygenases and 5-lipoxygenase in Alzheimer's disease.
AB  - Typically, cyclooxygenases (COXs) and 5-lipoxygenase (5-LOX), enzymes that
      generate biologically active lipid molecules termed eicosanoids, are considered
      inflammatory. Hence, their putative role in Alzheimer's disease (AD) has been
      explored in the framework of possible inflammatory mechanisms of AD pathobiology.
      More recent data indicate that these enzymes and the biologically active lipid
      molecules they generate could influence the functioning of the central nervous
      system and the pathobiology of neurodegenerative disorders such as AD via
      mechanisms different from classical inflammation. These mechanisms include the
      cell-specific localization of COXs and 5-LOX in the brain, the type of lipid
      molecules generated by the activity of these enzymes, the type and the
      localization of receptors selective for a type of lipid molecule, and the
      putative interactions of the COXs and 5-LOX pathways with intracellular
      components relevant for AD such as the gamma-secretase complex. Considering the
      importance of these multiple and not necessarily inflammatory mechanisms may help
      us delineate the exact nature of the involvement of the brain COXs and 5-LOX in
      AD and would reinvigorate the search for novel targets for AD therapy.

PMID- 20691750
TI  - Eight-year outcome of posterior inlay-retained all-ceramic fixed dental
      prostheses.
AB  - AIM: The main goal of this prospective clinical study was to evaluate the outcome
      of inlay-retained fixed dental prostheses (FDPs) made from heat-pressed lithium
      disilicate glass-ceramic. METHODS: Forty-five FDPs were placed in 42 patients (21
      women, mean age 36.1 years and 21 men, mean age 42.0 years). The FDPs replaced 4
      premolars and 19 molars in the maxilla and 4 premolars and 18 molars in the
      mandible. Preparations were performed in accordance with general principles for
      ceramic inlay restorations. Five of the 45 FDPs were hybrid-retained
      restorations, i.e. one abutment tooth with an inlay retainer and one with a full
      crown retainer. All FDPs were pressed in one piece using lithium-disilicate
      ceramic (IPS e.max Press, Ivoclar Vivadent). The minimum dimensions for the
      proximal connector were 4mm in height and 4mm in width (16 mm(2)) with a minimum
      occlusal ceramic thickness of 1.5mm. The surfaces of the inlay retainer were
      conditioned by etching with hydrofluoric acid 5% and silane application. Standard
      adhesive luting techniques were performed using a dentin adhesive (Syntac
      Classic, Ivoclar Vivadent) and a resin composite (Variolink II, Ivoclar
      Vivadent). Clinical follow-up examinations were performed annually. RESULTS: The
      mean observation periods were 70 months (minimum 4, maximum 123 months). Twenty
      seven FDPs (60%) failed during the observation period and had to be replaced. The
      Kaplan-Meier survival rate for inlay-retained FDPs was 57% after 5 years and 38%
      after 8 years, while for hybrid-retained FDPs it was 100% after 5 and 60% after 8
      years. CONCLUSIONS: Inlay-retained FDPs made from lithium-disilicate ceramic
      present a high clinical failure rate and therefore cannot be recommended.

PMID- 20691751
TI  - Cervical intraepithelial neoplasia: Telomerase activity and splice pattern of
      hTERT mRNA.
AB  - Cervical cancers are characterized by the persistence of human papilloma virus
      (HPV) genome that is found in tissue samples starting from the early stages of
      tumor progression. Just like in other tumors, the activation of telomerase was
      observed in cervical carcinomas, but information about its expression was
      controversial. The aim of this study is to find possible correlations between the
      presence of HPV sequences, activity of telomerase and expression of different
      spliced forms of hTERT RNA in cervical intraepithelial neoplasias (CIN). The
      results show that HPV DNA is present in 60% of normal tissue adjacent to CIN
      lesions and up to 84% in CIN samples. Telomerase activity was found in 28% of
      adjacent normal tissue and in 68% of CIN II-III. hTERT RNA that encodes an active
      enzyme was present almost in all CIN samples. Variations in levels of telomerase
      activity are possibly not regulated by the splicing forms of hTERT mRNA with
      deletions.

PMID- 20691752
TI  - Immunohistochemical localization of calbindin D28-k, parvalbumin, and calretinin
      in the cerebellar cortex of the circling mouse.
AB  - The spontaneous mutant circling mouse has an autosomal recessive pattern of
      inheritance and is an animal model for deafness, which is characterized by
      circling, head tossing, and hyperactivity. Since the main pathology in circling
      mice lies in the organ of Corti, most studies on deaf mice have focused on
      auditory brain stem nuclei. No studies regarding behavior-related CNS changes in
      circling mice have been reported. The major center of sensory input for
      modulation of motor activity is best-studied in the cerebellum. Considering the
      importance of calcium homeostasis in numerous processes, calcium-binding proteins
      (CaBPs), such as calbindin D-28k (CB), parvalbumin (PV), and calretinin (CR), may
      play crucial roles in preserving cerebellar coordinated motor function. Thus, the
      distribution of CB, PV, and CR was determined in the cerebellum using
      immunohistochemical methods to compare immunoreactivity (IR) of CaBPs between
      wild-type (+/+), heterozygous (+/cir), and homozygous (cir/cir) mice. The IR of
      CB and PV was predominantly observed in the Purkinje cell layer of all three
      genotypes. Compared with the +/+ genotype, the relative mean density of CB and PV
      IR in the Purkinje cell layer and CR IR in the granular layer was significantly
      decreased in the cir/cir genotype. Changes in calcium homeostasis in parallel
      fiber/Purkinje cell synapses could diminish cerebellar control of motor
      coordination. A number of deficiencies among the CaBPs lead to distinct
      alterations in brain physiology, which may affect normal behavior.

PMID- 20691753
TI  - Involvement of dorsal hippocampal alpha1-adrenergic receptors in the effect of
      WIN55,212-2 on memory retrieval in inhibitory avoidance task.
AB  - In the present study, the possible role of alpha1-adrenergic receptors of the
      dorsal hippocampus on WIN55,212-2-induced amnesia in male Wistar rats has been
      evaluated. As a model of learning, a step-down passive avoidance task was used.
      Results indicated that post-training or pre-test intra-CA1 administration of
      WIN55,212-2 (0.25 and 0.5 MUg/rat) reduced the step-down latency, showing an
      amnestic response. Amnesia produced by post-training WIN55,212-2 (0.5 MUg/rat)
      was reversed by pre-test administration of the same drug dose. Interestingly, pre
      test intra-CA1 administration of alpha1-noradrenergic agonists, phenylephrine
      alone or with an ineffective dose of WIN55,212-2 (0.25 MUg/rat) reversed post
      training WIN55,212-2 (0.5 MUg/rat)-induced retrieval impairment. On the other
      hand, pre-test intra-CA1 microinjection of an alpha1-adrenergic antagonist,
      prazosin (0.5 MUg/rat), 2 min before administration of WIN55,212-2 (0.5 MUg/rat)
      inhibited the pre-test WIN55,212-2 response. It may be concluded that alpha1
      adrenergic receptors of the dorsal hippocampal CA1 regions play an important role
      in WIN55,212-2-induced amnesia and restoration of memory by pre-test WIN55,212-2
      administration.

PMID- 20691754
TI  - Systemic administration of D-penicillamine prevents the locomotor activation
      after intra-VTA ethanol administration in rats.
AB  - Although recently published studies seem to confirm the important role displayed
      by acetaldehyde (ACH), the main metabolite of ethanol, in the behavioral effects
      of ethanol, the origin of ACH is still a matter of debate. While some authors
      confer more importance to the central (brain metabolism) origin of ACH, others
      indicate that the hepatic origin could be more relevant. In this study we have
      addressed this topic using an experimental approach that combines local
      microinjections of ethanol into the ventral tegmental area (VTA) (which
      guarantees the brain origin of the ACH) to induce motor activation in rats
      together with systemic administration (i.p.) of several doses (0, 12.5, 25 and 50
      mg/kg) of D-penicillamine (DP), a sequestering agent of ACH with contrasted
      efficiency to abolish the behavioral effects of the drug. Our results clearly
      show that DP prevented in a dose-dependent manner the motor activation induced by
      intra-VTA ethanol, being the 50 mg/kg dose the most efficient. DP per se did not
      affect the basal activity of the rats. In order to determine the specificity of
      the DP action, we also studied the effects of DP 50 mg/kg on the DAMGO-induced
      motor activation after the intra-VTA administration of this mu-opioid receptors
      agonist. DP did not significantly modify the motor activation induced by DAMGO
      thus confirming the specificity of the DP effects. Our results clearly suggest
      that the brain-derived ACH is necessary to manifest the activating effects
      resulting from ethanol administration.

PMID- 20691755
TI  - The effects of anesthesia on measures of nerve conduction velocity in male
      C57Bl6/J mice.
AB  - Animal models, particularly mice, are used extensively to investigate
      neurological diseases. Basic research regarding animal models of human
      neurological disease requires that the animals exhibit hall mark characteristics
      of the disease. These include disease specific anatomical, metabolic and
      behavioral changes. Nerve conduction velocity (NCV) is the predominant method
      used to assess peripheral nerve health. Normative data adjusted for age, gender
      and height is available for human patients; however, these data are not available
      for most rodents including mice. NCV may be affected by animal age and size, body
      temperature, stimulus strength and anesthesia. While the effects of temperature,
      age and size are documented, the direct and indirect effects of anesthesia on NCV
      are not well reported. Our laboratory is primarily concerned with animal models
      of diabetic neuropathy (DN) and uses NCV to confirm the presence of neuropathy.
      To ensure that subtle changes in NCV are reliably assayed and not directly or
      indirectly affected by anesthesia, we compared the effects of 4 commonly used
      anesthetics, isoflurane, ketamine/xylazine, sodium pentobarbital and 2-2-2
      tribromoethanol on NCV in a commonly used rodent model, the C57Bl6/J mouse. Our
      results indicate that of the anesthetics tested, isoflurane has minimal impact on
      NCV and is the safest, most effective method of anesthesia. Our data strongly
      suggest that isoflurane should become the anesthetic of choice when performing
      NCV on murine models of neurological disease.

PMID- 20691756
TI  - The extinction of morphine-induced conditioned place preference by histone
      deacetylase inhibition.
AB  - Recent evidence suggests that epigenetic mechanisms have an important role in the
      development of addictive behavior. However, little is known about the role of
      epigenetic mechanisms in the extinction of morphine-induced behavioral changes.
      In this study, we will examine the effect of histone deacetylase (HDAC)
      inhibitors on extinction of morphine-induced conditioned place preference (CPP).
      To facilitate extinction, rats will be administered an HDAC inhibitor (HDACi)
      following nonreinforced exposure to the conditioned context. To measure
      persistence, rats were subject to a reinstatement test using 3 mg/kg dose of
      morphine. To exclude the effect of repeated NaBut injections themselves on
      morphine-CPP in the absence of extinction session, rats received injection of
      either NaBut or vehicle for 8 days. We found that HDAC inhibition during
      nonconfined extinction or confined extinction consolidation can facilitate
      extinction of morphine-induced CPP. We also showed that the extinction of drug
      seeking via HDAC inhibition modulates extinction learning such that reinstatement
      behavior is significantly attenuated. There is no effect of repeated NaBut
      injections themselves on morphine-CPP in the absence of extinction session. In
      conclusion, our results extend earlier reports on the ability of HDACi to modify
      the behavioral effects of drugs of abuse. Our increasing understanding of these
      epigenetic mechanisms will provide key answers to basic processes in drug
      addiction and hopefully provide insight into designing improved treatments for
      drug addiction.

PMID- 20691757
TI  - Protective effects of the citrus flavanones to PC12 cells against cytotoxicity
      induced by hydrogen peroxide.
AB  - Oxidative stress has been considered as a major cause of cellular injuries in a
      variety of clinical abnormalities. One of the plausible ways to prevent the
      reactive oxygen species (ROS)-mediated cellular injury is dietary or
      pharmaceutical augmentation of endogenous antioxidant defense capacity. In this
      study, we investigated the protective actions of citrus flavanones naringin and
      nobiletin against the cytotoxicity induced by exposure to hydrogen peroxide
      (H(2)O(2)) (150MUM, 3h) in PC12 cells. The results showed that naringin and
      nobiletin inhibited the decrease of cell viability (MTT reduction), prevented
      membrane damage (LDH release), scavenged ROS formation, reduced caspase-3
      activity, and attenuated the decrease of mitochondrial membrane potential (MMP),
      respectively, in H(2)O(2)-induced PC12 cells. Meanwhile, naringin and nobiletin
      increased superoxide dismutase (SOD) and glutathione (GSH) activity, while
      decreased malondialdehyde (MDA), the production of lipid peroxidation, in
      H(2)O(2)-induced PC12 cells. In addition, the percentage of cells undergoing
      H(2)O(2)-induced apoptosis was decreased in the presence of naringin and
      nobiletin. These results first demonstrate that naringin and nobiletin, even at
      physiological concentrations, have neuroprotective effects against H(2)O(2)
      induced cytotoxicity in PC12 cells. All the above results suggest that these
      dietary antioxidants are potential candidates for use in the intervention for
      neurodegenerative diseases.

PMID- 20691758
TI  - Aging and antioxidants modulate rat brain levels of homocysteine and
      dehydroepiandrosterone sulphate (DHEA-S): implications in the pathogenesis of
      Alzheimer's disease.
AB  - The study has shown that in aged (22-24 months) rat brains an elevation of
      homocysteine level (42%) and a decrease in dehydroepiandrosterone sulphate (DHEA
      S) content (32%) occur compared to those in the brains of young rats (4-6
      months). Such changes in the brain levels of homocysteine and DHEA-S in aged rats
      are prevented, when the diet daily of the rats is supplemented with a combination
      of antioxidants (N-acetyl cysteine 50 mg, alpha-lipoic acid 3 mg and alpha
      tocopherol 1.5 mg - each per 100 g of body weight) starting from 18 months until
      these are sacrificed between 22 and 24 months. The brain content of reduced
      glutathione is also decreased in aged rats as compared to that in young ones and
      the phenomenon can again be prevented completely by the same regimen of
      antioxidant supplementation. The changes in the levels of homocysteine and DHEA-S
      in aged rat brain have been related to associated glutathione depletion and
      oxidative stress and the implications of the results highlighted in the
      pathogenesis of Alzheimer's disease.

PMID- 20691759
TI  - Descriptive findings on the morphology of dendritic spines in the rat medial
      amygdala.
AB  - The rat posterodorsal medial amygdala (MePD) is a brain area in which gonadal
      hormones induce notable plastic effects in the density of dendritic spines.
      Dendritic spines are post-synaptic specializations whose shape and spacing change
      neuronal excitability. Our aim was to obtain new data on the dendritic spines
      morphology and density from MePD neurons using the carbocyanine dye DiI under
      confocal microscopy. In adult male rats, the dendritic spine density of the
      medial branches of the left MePD (mean+/-SD) was 1.15+/-0.67spines/dendritic
      microm. From the total sampled, approximately 53% of the spines were classified
      as thin, 22.5% as "mushroom-like", and 21.5% as stubby/wide. Other spine shapes
      (3%) included those ramified, with a filopodium-like or a gemule appearance, and
      others with a protruding spinule. Additional experiment joining DiI and
      synaptophysin (a pre-synaptic protein) labeling suggested synaptic sites on
      dendritic shafts and spines. Dendritic spines showed synaptophysin puncta close
      to their head and neck, although some spines had no evident labeled puncta on
      them or, conversely, multiple puncta appeared upon one spine. These results
      advance previous light microscopy results by revealing features and complexities
      of the dendritic spines at the same time that give new insight on the possible
      synaptic organization of the adult rat MePD.

PMID- 20691760
TI  - Cued and spatial learning in the water maze: equivalent learning in male and
      female mice.
AB  - Mammals navigate a complex environment using a variety of strategies, which can
      operate in parallel and even compete with one another. We have recently described
      a variant water maze task in which two of these strategies, hippocampus-dependent
      spatial learning and striatum-dependent cued learning, can be dissociated. Male
      rodents perform better at some spatial learning tasks, while female rodents more
      readily learn certain striatum-dependent behavioral strategies. We therefore
      predicted that sex would differentially influence spatial and cued learning in
      the water maze. We trained adult male and female C57Bl/6 mice for 7 days in the
      two-cue variant of the water maze, with probe trials on days 5 and 7. In two
      independent experiments, males and females performed similarly, with both groups
      showing good spatial learning after 5 and 7 days of training, and both groups
      showing trend-level cued learning after 5 days and robust learning after 7.
      Therefore, contrary to our hypothesis, sex does not significantly affect cued or
      spatial learning in this task.

PMID- 20691761
TI  - A study of cytokines in tuberculous meningitis: clinical and MRI correlation.
AB  - There is paucity of studies on cytokines in tuberculous meningitis (TBM) and
      their relation with clinical and radiological changes; therefore this study was
      undertaken. 16 TBM patients diagnosed on the basis of clinical, CSF and
      radiological criteria were included. They were subjected to TNF-alpha, IL-6, IL
      8, IL-10, IL-1beta, and IL-12p70 estimation in CSF. The cytokine levels were also
      estimated in 10 controls. Initial clinical examination, stage of TBM and MRI
      findings (infarct, hydrocephalus, tuberculoma and exudates) were recorded. The
      patients were treated with 4 drugs antitubercular (RHZE) therapy and after 3
      months clinical examination, cytokine levels, and radiological studies were
      repeated. Outcome was defined by Barthel index score at 3 months into poor,
      partial and complete recovery. The patient's age ranged between 10 and 50 years,
      5 were females. At 3 months, all the patients were clinically followed up and 14
      underwent repeat MRI. 10 patients improved, 1 remained stable and 5 deteriorated.
      There was worsening with respect to tuberculoma in 3, infarction in 2 and exudate
      in 1 patient. TNF-alpha was expressed in 32% patients, IL-6, IL-10, IL-1beta and
      IL-8 were significantly expressed in patients and declined after 3 months
      following treatment. The cytokine levels did not correlate with stage of
      meningitis, outcome and radiological deterioration or improvement.

PMID- 20691762
TI  - State-dependent sculpting of olfactory sensory neurons is attributed to sensory
      enrichment, odor deprivation, and aging.
AB  - Gene-targeted deletion of the predominant Shaker potassium channel, Kv1.3, in the
      mitral cells of the olfactory bulb, decreases the number of presynaptic, odorant
      receptor (OR)-identified olfactory sensory neurons (OSNs) in the main olfactory
      epithelium (MOE) and alters the nature of their postsynaptic connections to
      mitral cell targets. The current study examined whether OSN density was state
      dependent by examining the impact of (1) odor enrichment, (2) sensory
      deprivation, and (3) aging upon the number of P2- or M72-expressing neurons.
      Histological approaches were used to quantify the number of OSNs across entire
      epithelia for wildtype (WT) vs. Kv1.3-null (KO) mice bred onto an ORtauLacZ
      reporter background. Following either odor enrichment or early unilateral naris
      occlusion, the number of M72-expressing OSNs was significantly decreased in WT
      mice, but was unchanged in KO animals. Following naris-occlusion, the number of
      P2-expressing OSNs was decreased regardless of genotype. Animals that were reared
      to 2 years of age demonstrated loss of both P2- and M72-expressing OSNs in WT
      mice and a concomitant loss of only M72-expressing neurons in KO mice. These
      findings suggest that voltage-gated activity of the mitral cells is important for
      OSN plasticity, and can prevent neuronal loss via sensory- and OR-dependent
      mechanisms.

PMID- 20691763
TI  - Distribution and neurochemical characterization of protein kinase C-theta and 
      delta in the rodent hypothalamus.
AB  - PKC-theta (PKC-theta), a member of the novel protein kinase C family (nPKC),
      regulates a wide variety of functions in the periphery. However, its presence and
      role in the CNS has remained largely unknown. Recently, we demonstrated the
      presence of PKC-theta in the arcuate hypothalamic nucleus (ARC) and knockdown of
      PKC-theta from the ARC protected mice from developing diet-induced obesity.
      Another isoform of the nPKC group, PKC-delta (PKC-delta), is expressed in several
      non-hypothalamic brain sites including the thalamus and hippocampus. Although PKC
      delta has been implicated in regulating hypothalamic glucose homeostasis, its
      distribution in the hypothalamus has not previously been described. In the
      current study, we used immunohistochemistry to examine the distribution of PKC
      theta and -delta immunoreactivity in rat and mouse hypothalamus. We found PKC
      theta immunoreactive neurons in several hypothalamic nuclei including the ARC,
      lateral hypothalamic area, perifornical area and tuberomammillary nucleus. PKC
      delta immunoreactive neurons were found in the paraventricular and supraoptic
      nuclei. Double-label immunohistochemisty in mice expressing green fluorescent
      protein either with the long form of leptin receptor (LepR-b) or in orexin (ORX)
      neurons indicated that PKC-theta is highly colocalized in lateral hypothalamic
      ORX neurons but not in lateral hypothalamic LepR-b neurons. Double-label
      immunohistochemistry in oxytocin-enhanced yellow fluorescent protein mice or
      arginine vasopressin-enhanced green fluorescent protein (AVP-EGFP) transgenic
      rats revealed a high degree of colocalization of PKC-delta within paraventricular
      and supraoptic oxytocin neurons but not the vasopressinergic neurons. We conclude
      that PKC-theta and -delta are expressed in different hypothalamic neuronal
      populations.

PMID- 20691764
TI  - Sleep consolidates the effector-independent representation of a motor skill.
AB  - During off-line consolidation a motor skill becomes less vulnerable to
      interference (stabilisation) and improves in performance (enhancement). Here we
      examined whether off-line consolidation contributes to the process of
      generalisation in the extrinsic and intrinsic coordinate frame in the motor
      domain. Participants trained with the left hand a sequential finger tapping task
      that has proved sensitive to off-line consolidation. Generalisation was tested by
      the ability to transfer the original sequence (extrinsic transformation) or the
      mirror sequence (intrinsic transformation) to the right hand, and this was
      compared with performance on a new sequence not learned before. To determine
      acute effects on generalisation, transfer was assessed immediately after training
      of the left hand. To study the effects of off-line consolidation participants
      were tested after an interval of daytime (training at 8 am and retrieval test on
      the transfer sequences at 8 pm) or after an interval of night-time sleep
      (training at 8 pm and retrieval test on the transfer sequences at 8 am). Acutely,
      training of the left hand induced significant transfer effects to the right hand
      for the extrinsic transformation of the sequence, but there was no advantage for
      the intrinsic transformation. After a period of daytime wakefulness the transfer
      from the left to the right hand for the extrinsic sequence transformation had
      vanished and, again, there was no transfer effect for the intrinsic
      transformation of the sequence. By contrast, nocturnal sleep saved the initial
      transfer effect for the extrinsic sequence transformation. The intrinsic sequence
      transformation was not affected by sleep. Our results show that an effector
      independent representation in an extrinsic co-ordinate frame of a skill develops
      soon after initial training. Sleep has the capacity to consolidate this transfer
      and, in this way, contributes to the generalisation of a motor skill.

PMID- 20691766
TI  - Extension of the neuroprotective time window for thiazolidinediones in ischemic
      stroke is dependent on time of reperfusion.
AB  - Stroke is a leading cause of death and disability but has limited therapeutic
      options. Thiazolidinediones (TZDs), agonists for the nuclear receptor, peroxisome
      proliferator-activated receptor (PPAR)gamma, reduce infarct volume and improve
      neurologic function following transient middle cerebral artery occlusion (MCAO)
      in rats. Translation of these findings into clinical therapy will require careful
      assessment of dosing paradigms and effective time windows for treatment.
      Understanding the mechanisms by which TZDs protect the brain provides insight
      into how time windows for neuroprotection might be extended. We find that two
      TZDs, pioglitazone and rosiglitazone, significantly reduce infarct volume at
      doses similar to those used clinically (1 mg/kg for pioglitazone and 0.1 mg/kg
      for rosiglitazone). We also find that pioglitazone reduces infarction volume in a
      transient, but not a permanent MCAO model suggesting that reperfusion plays an
      important role in TZD mediated neuroprotection. Since PPARgamma agonists reduce
      inflammation and oxidative stress, both of which are exacerbated by reperfusion,
      we hypothesized that TZDs would be most effective if administered prior to
      reperfusion. We administered TZDs 3 h after MCAO and found that infarction volume
      and neurologic function are significantly improved in animals reperfused at 3 h
      and 15 min (after TZD treatment), but not in animals reperfused at 2 h (before
      TZD treatment) when assessed either 24 h or 3 weeks after MCAO. While TZDs reduce
      intercellular adhesion molecule (ICAM) expression to a similar extent regardless
      of the time of reperfusion, leukocyte entry into brain parenchyma is more
      dramatically reduced when reperfusion is delayed until after drug treatment. The
      finding that delaying reperfusion until after TZD treatment is beneficial despite
      a longer period of ischemia, is dramatic given the widely held view that duration
      of ischemia is the most important determinate of injury.

PMID- 20691767
TI  - Basal dendrites are present in newly born dentate granule cells of young but not
      aged pilocarpine-treated chronic epileptic rats.
AB  - Epilepsy is known to influence hippocampal dentate granule cell (DGC) layer
      neurogenesis. In young adult rats, status epilepticus (SE) increases the number
      DGC newly borne cells and basal dendrites (BD), which persist at long-term. In
      contrast, little is known on whether these phenomena occur in elderly epileptic
      animals. In the present study, we compare DGC proliferation and the incidence of
      BD in young and aged pilocarpine-treated rats. Three epileptic groups were
      considered: Young animals given pilocarpine at 3 months of age. Aged animals
      treated with pilocarpine at 3 months of age that were sacrificed at 17-20 months.
      Aged animals that had pilocarpine and developed SE at 20 months, being sacrificed
      2 months later. Nine days prior to sacrifice, animals underwent swimming sessions
      in the Morris water maze as a protocol for the development of hippocampal
      neurogenesis. We found a higher incidence of newly born DGC cells in young as
      compared to aged epileptic animals (P<0.001). This later group however, was not
      homogeneous. While a significant increase in DGC neurogenesis was observed when
      aged animals with long lasting epilepsy were compared to non-epileptic controls
      (P<0.01), this has not been recorded in aged animals that had epilepsy for only 2
      months (P>0.05). When the number of DGC containing BD was considered, a
      significantly higher incidence was observed in young as compared to aged
      epileptic rats (P=0.001). Animals in this later group virtually lacked BD in
      newly formed dentate gyrus (DG) cells. Based on these results we conclude that
      plastic changes during epileptogenesis and the development of a pathological
      substrate in young animals is associated with DGC proliferation and the emergence
      of BD. As aging occurs, DGC neurogenesis can still be induced in rats with a long
      term history of epilepsy but the emergence of BD is markedly reduced.

PMID- 20691765
TI  - Inhibition of cerebellar granule cell turning by alcohol.
AB  - Ectopic neurons are often found in the brains of fetal alcohol spectrum disorders
      (FASD) and fetal alcohol syndrome (FAS) patients, suggesting that alcohol
      exposure impairs neuronal cell migration. Although it has been reported that
      alcohol decreases the speed of neuronal cell migration, little is known about
      whether alcohol also affects the turning of neurons. Here we show that ethanol
      exposure inhibits the turning of cerebellar granule cells in vivo and in vitro.
      First, in vivo studies using P10 mice demonstrated that a single intraperitoneal
      injection of ethanol not only reduces the number of turning granule cells but
      also alters the mode of turning at the EGL-ML border of the cerebellum. Second,
      in vitro analysis using microexplant cultures of P0-P3 mouse cerebella revealed
      that ethanol directly reduces the frequency of spontaneous granule cell turning
      in a dose-dependent manner. Third, the action of ethanol on the frequency of
      granule cell turning was significantly ameliorated by stimulating Ca(2+) and cGMP
      signaling or by inhibiting cAMP signaling. Taken together, these results indicate
      that ethanol affects the frequency and mode of cerebellar granule cell turning
      through alteration of the Ca(2+) and cyclic nucleotide signaling pathways,
      suggesting that the abnormal allocation of neurons found in the brains of FASD
      and FSA patients results, at least in part, from impaired turning of immature
      neurons by alcohol.

PMID- 20691768
TI  - Increased response of muscle sensory neurons to decreases in pH after muscle
      inflammation.
AB  - Acid sensing ion channels (ASIC) are found in sensory neurons, including those
      that innervate muscle tissue. After peripheral inflammation there is an increase
      in proton concentration in the inflamed tissue, which likely activates ASICs.
      Previous studies from our laboratory in an animal model of muscle inflammation
      show that hyperalgesia does not occur in ASIC3 and ASIC1 knockout mice.
      Therefore, in the present study we investigated if pH activated currents in
      sensory neurons innervating muscle are altered after induction of muscle
      inflammation. Sensory neurons innervating mouse (C57/Bl6) muscle were
      retrogradely labeled with 1,1-dioctadecyl-3,3,3,3 tetramethylindocarbocyanine
      perchlorate (DiI). Two weeks after injection of DiI, mice were injected with 3%
      carrageenan to induce inflammation (n=8; 74 neurons) or pH 7.2 saline (n=5; 40
      neurons, control) into the gastrocnemius muscle. 24 h later sensory neurons from
      L4-L6 dorsal root ganglia (DRG) were isolated and cultured. The following day the
      DRG neuron cultures were tested for responses to pH by whole-cell patch-clamp
      technique. Approximately 40% of neurons responded to pH 5 with an inward rapidly
      desensitizing current consistent with ASIC channels in both groups. The mean pH
      evoked current amplitudes were significantly increased in muscle sensory neurons
      from inflamed mice (pH 5.0, 3602 +/- 470 pA) in comparison to the controls (pH
      7.4, 1964 +/- 370 pA). In addition, the biophysical properties of ASIC-like
      currents were altered after inflammation. Changes in ASIC channels result in
      enhanced responsiveness to decreases in pH, and likely contribute to the
      increased hyperalgesia observed after muscle inflammation.

PMID- 20691769
TI  - Estrogen-induced activation of extracellular signal-regulated kinase signaling
      triggers dendritic resident mRNA translation.
AB  - Activated extracellular signal-regulated kinase (ERK) signaling mediated
      plasticity-related gene transcription has been proposed for one possible
      mechanism by which 17beta-estradiol (E2) enhances synaptic plasticity and memory.
      Because activated ERK also enhances plasticity-related mRNA translation in the
      dendrites of neurons, we sought to determine the effects of E2 on activation of
      ERK, phosphorylation of translation initiation factors, and dendritic mRNA
      translation in hippocampal neurons. Acute E2 application resulted in a rapid,
      transient increase in phosphorylation of translation initiation factors,
      ribosomal protein (S6) and eIF4E binding protein1 (4EBP1), in an activated ERK
      dependent manner. Since phosphorylation of these translation factors enhance mRNA
      translation, we tested E2's effect on dendritic mRNA translation. Using a green
      fluorescent protein (GFP)-based dendritic mRNA translation reporter (reporter
      plasmid construct consisted of a GFP gene fused to the 3' untranslated region
      (UTR) from CAMKIIalpha, which contains dendritic resident mRNA targeting and mRNA
      translational regulatory elements) we showed that E2 treatment resulted in
      increased somatic and dendritic GFP mRNA translation in GFP-reporter transfected
      hippocampal neurons. Translation inhibitor anisomycin and ERK inhibitor U0126
      blocked E2 effects. Taken together, our results provide a novel mechanism by
      which E2 may trigger local protein synthesis of alpha-CaMKII in the dendrites,
      which is necessary for modulation of synaptic plasticity.

PMID- 20691770
TI  - Neonatal maternal separation exacerbates the reward-enhancing effect of acute
      amphetamine administration and the anhedonic effect of repeated social defeat in
      adult rats.
AB  - Early life adversity or parental neglect is linked to the development of a number
      of psychiatric illnesses, including major depression and substance use disorder.
      These two disorders are often comorbid and characterized by anhedonia, defined as
      the reduced ability to experience pleasure or reward. The aim of the present
      study was to determine the effects of neonatal maternal separation in Long Evans
      rats, a model of early life stress, on anhedonia under baseline conditions and in
      response to drug and stress exposure during adulthood. Three hours of daily
      maternal separation from postnatal day 1 to 14 led to marked decreases in arched
      back nursing, licking, and grooming of pups by their dams. In adulthood, brain
      reward function was assessed using intracranial self-stimulation of the lateral
      hypothalamus. Lowered current thresholds derived from this procedure are
      interpreted as reward-enhancing effects, whereas elevations in thresholds are an
      operational measure of anhedonia. Maternally separated rats did not exhibit
      anhedonia under baseline conditions compared with non-handled controls but
      exhibited a greater reward-enhancing effect of acute amphetamine administration.
      Acute social defeat produced anhedonia in non-handled controls, but not in
      maternally separated rats. Conversely, control rats habituated to 7 days of
      repeated social defeat, whereas maternally separated rats developed an increased
      anhedonic response to the repeated stressor. One week after termination of stress
      exposure, maternally separated rats still exhibited an increased reward-enhancing
      effect of acute amphetamine administration compared with non-handled controls,
      regardless of prior social defeat experience. These data indicate that early life
      stress increases the reward-enhancing properties of amphetamine, protects against
      the anhedonic effects of acute stress exposure, and exacerbates the anhedonic
      response to repeated stress. Thus, early life stress may increase an individual's
      vulnerability to depressive or addictive disorders when confronted with stress or
      drug challenge in adulthood.

PMID- 20691771
TI  - Insulin facilitates repetitive spike firing in rat insular cortex via
      phosphoinositide 3-kinase but not mitogen activated protein kinase cascade.
AB  - The insular cortex (IC) processes gustatory and visceral information, which
      functionally correlate to feeding behavior. Insulin, a well-known hormone
      controlling glucose metabolism, is released by elevation of blood glucose
      concentration following feeding behavior. The IC expresses dense insulin
      receptors and receives projection from the hypothalamus, which monitors changes
      in glucose concentration. Therefore, it is likely that insulin modulates neural
      properties in the IC. However, little is known about the effects of insulin on
      electrophysiological properties of the neocortex including the IC. To explore the
      effects of insulin on subthreshold responses and action potential properties in
      the IC, intracellular recording with sharp glass electrodes was performed from IC
      pyramidal cells using slice preparations. Although application of insulin (100
      nM) had little effect on the resting membrane potential, input resistance and
      rheobase, insulin significantly increased the frequency of repetitive spike
      firing in response to a long depolarizing current pulse injection: the slope of
      the frequency-current curve was increased from 23.7+/-2.3 Hz/nA to 29.5+/-3.4
      Hz/nA. Insulin slightly decreased the action potential threshold without
      affecting the amplitude of medium-duration and slow afterhyperpolarization (sAHP)
      s. The insulin-induced facilitation of repetitive spike firing was dose-dependent
      and blocked by pre-application of 200 nM lavendustin A, a tyrosine kinase
      inhibitor. Moreover, when combined with 200 nM wortmannin, a phosphoinositide 3
      kinase (PI3-K) inhibitor, or 500 nM deguelin, an inhibitor of protein kinase B
      (PKB/Akt) downstream of PI3-K, insulin failed to increase the frequency of
      repetitive spike firing. In contrast, co-application of insulin and (10 MUM) PD
      98059, an inhibitor of mitogen activated protein kinase (MAPK), exerted
      facilitation of repetitive spike firing. These results suggest that acute insulin
      induced facilitation of firing frequency is at least partially induced by
      hyperpolarizing effects on the action potential threshold, and that this
      facilitation is induced by activation of PI3-K but not MAPK cascade.

PMID- 20691773
TI  - The ethyl acetate extract of PGP (Phellinus linteus grown on Panax ginseng)
      suppresses B16F10 melanoma cell proliferation through inducing cellular
      differentiation and apoptosis.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Phellinus linteus and Panax ginseng have been
      widely used as traditional herbal medicines to treat various diseases including
      cancer in East Asia. AIM OF THE STUDY: The present study sought to investigate
      the possible mechanism in anti-proliferative effect of Phellinus linteus that was
      grown on Panax ginseng (PGP) on B16F10 melanoma cells. MATERIALS AND METHODS: The
      anti-proliferative effect of PGP on B16F10 was evaluated by CCK-8 assays.
      Apoptotic cells were detected by flow cytometry analysis. The proteins involved
      in apoptosis and cellular differentiation were assessed by immunoblot analysis.
      Ginsenosides contents of PG or PGP were analyzed using HPLC. RESULTS: The ethyl
      acetate fraction (EtOAc) of PGP exhibited the strongest anti-proliferative
      activity among PGP fractions (butanol or water) on B16F10 cells. PGP EtOAc
      extract showed stronger inhibitory effect than Panax ginseng (PG) or Phellinus
      linteus (PL) EtOAc extract on B16F10 melanoma cell proliferation. PGP EtOAc
      extract induced the dendrite-like structures and the melanin production in B16F10
      cells. PGP EtOAc extract increased a sub-G1 cell population through inducing
      p53/p21 and activated caspase-8 protein expression in B16F10 cells. Notably, PGP
      EtOAc extract contained ginsenosides Rd, Rg3, Rb2, Rg1 and Rb1 more than PG EtOAc
      extract. Rd and Rg3 significantly inhibited B16F10 cell proliferation.
      CONCLUSION: Our data suggest that PGP EtOAc extract inhibits B16F10 cell
      proliferation through inducing apoptosis and cellular differentiation.

PMID- 20691772
TI  - Detecting novel genes with sparse arrays.
AB  - Species-specific genes play an important role in defining the phenotype of an
      organism. However, current gene prediction methods can only efficiently find
      genes that share features such as sequence similarity or general sequence
      characteristics with previously known genes. Novel sequencing methods and tiling
      arrays can be used to find genes without prior information and they have
      demonstrated that novel genes can still be found from extensively studied model
      organisms. Unfortunately, these methods are expensive and thus are not easily
      applicable, e.g., to finding genes that are expressed only in very specific
      conditions. We demonstrate a method for finding novel genes with sparse arrays,
      applying it on the 33.9 Mb genome of the filamentous fungus Trichoderma reesei.
      Our computational method does not require normalisations between arrays and it
      takes into account the multiple-testing problem typical for analysis of
      microarray data. In contrast to tiling arrays, that use overlapping probes, only
      one 25 mer microarray oligonucleotide probe was used for every 100b. Thus, only
      relatively little space on a microarray slide was required to cover the
      intergenic regions of a genome. The analysis was done as a by-product of a
      conventional microarray experiment with no additional costs. We found at least 23
      good candidates for novel transcripts that could code for proteins and all of
      which were expressed at high levels. Candidate genes were found to neighbour ire1
      and cre1 and many other regulatory genes. Our simple, low-cost method can easily
      be applied to finding novel species-specific genes without prior knowledge of
      their sequence properties.

PMID- 20691774
TI  - In vitro antifungal activity of indirubin isolated from a South Indian
      ethnomedicinal plant Wrightia tinctoria R. Br.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Acalypha indica, Cassia alata, Lawsonia inermis,
      Punica granatum, Thespesia populnea and Wrightia tinctoria are folklore medicines
      extensively used in the treatment of ringworm infections and skin related
      diseases in Tamil Nadu, India. AIM: The present study was designed to investigate
      the in vitro antifungal activity of certain medicinal plants and the pure
      compound indirubin isolated from Wrightia tinctoria. MATERIALS AND METHODS: The
      hexane, chloroform, methanol and ethanol extracts of six different plants were
      investigated against dermatophytes, non-dermatophytes and yeasts. Chloroform
      extract of Wrightia tinctoria leaf was fractionated using column chromatography
      and the major compound was identified using spectroscopic techniques. Antifungal
      activity was studied by spore germination test using agar dilution method. The
      minimum inhibitory concentration (MIC) was determined using broth microdilution
      method. RESULTS: Wrightia tinctoria showed promising activity against
      dermatophytic and non-dermatophytic fungi. Leaf chloroform extract showed
      activity at 0.5 mg/ml against Trichophyton rubrum, Epidermophyton floccosum,
      Aspergillus niger and Scopulariopsis brevicaulis. The major compound, identified
      as indirubin, exhibited activity against dermatophytes such as Epidermophyton
      floccosum (MIC=6.25 MUg/ml); Trichophyton rubrum and Trichophyton tonsurans
      (MIC=25 MUg/ml); Trichophyton mentagrophytes and Trichophyton simii (MIC=50
      MUg/ml). It was also active against non-dermatophytes (Aspergillus niger, Candida
      albicans and Cryptococcus sp.) within a MIC range of 0.75-25 MUg/ml. CONCLUSION:
      The indole compound indirubin from Wrightia tinctoria showed antifungal activity
      and may be useful in the treatment of dermatophytosis.

PMID- 20691775
TI  - Changes in gene expression after phencyclidine administration in developing rats:
      a potential animal model for schizophrenia.
AB  - Repeated administration of phencyclidine (PCP), an N-methyl-d-aspartate (NMDA)
      receptor antagonist, during development, may result in neuronal damage that leads
      to behavioral deficits in adulthood. The present study examined the potential
      neurotoxic effects of PCP exposure (10mg/kg) in rats on postnatal days (PNDs) 7,
      9 and 11 and the possible underlying mechanism(s) for neurotoxicity. Brain tissue
      was harvested for RNA extraction and morphological assessments. RNA was collected
      from the frontal cortex for DNA microarray analysis and quantitative RT-PCR. Gene
      expression profiling was determined using Illumina Rat Ref-12 Expression
      BeadChips containing 22,226 probes. Based on criteria of a fold-change greater
      than 1.4 and a P-value less than 0.05, 19 genes including NMDAR1 (N-methyl-d
      aspartate receptor) and four pro-apoptotic genes were up-regulated, and 25 genes
      including four anti-apoptotic genes were down-regulated, in the PCP-treated
      group. In addition, the schizophrenia-relevant genes, Bdnf (Brain-derived
      neurotrophic factor) and Bhlhb2 (basic helix-loop-helix domain containing, class
      B, 2), were significantly different between the PCP and the control groups.
      Quantitative RT-PCR confirmed the microarray results. Elevated neuronal cell
      death was further confirmed using Fluoro-Jade C staining. These findings support
      the hypothesis that neurodegeneration caused by PCP occurs, at least in part,
      through the up-regulation of NMDA receptors, which makes neurons possessing these
      receptors more vulnerable to endogenous glutamate. The changes in schizophrenia
      relevant genes after repeated PCP exposure during development may provide
      important information concerning the validation of an animal model for this
      disorder.

PMID- 20691776
TI  - Developmental PCB exposure induces hypothyroxinemia and sex-specific effects on
      cerebellum glial protein levels in rats.
AB  - Polychlorinated biphenyls (PCBs) are persistent lipophilic environmental
      contaminants which are found in fatty tissues of humans and wild-life alike.
      Maternal transfer of PCBs to offspring is easily achieved across the placenta and
      via lactation. In male rats, perinatal PCB exposure induces behavioral
      abnormalities, in addition to hypothyroxinemia and white matter changes. There
      are sex differences in white matter volume synthesis and density in adult and
      aged rodents. Yet whether PCB exposure effects on white matter are sex-specific
      is unclear, because the previous studies were conducted in male offspring.
      Furthermore, although hypothyroxinemia induced by PCB exposure is thought to
      trigger white matter changes, PCBs also affect interleukin-6 (IL-6) expression,
      and IL-6 regulates white matter growth. We hypothesized that perinatal PCB
      exposure would have sex-specific effects on white matter development associated
      with altered IL-6 levels. We found that female offspring had higher levels of
      myelin basic protein (MBP) than males did, at postnatal day (PND) 7, 18 and 21.
      PCB exposure induced hypothyroxinemia in males and females at PND7, 14, 21, and
      42. PCB exposure also increased MBP and reduced glial fibrillary acidic protein
      (GFAP) levels in males at PND21, but had the opposite effect in females. In
      addition, at PND14 and 21, PCB exposure elevated IL-6 levels in male offspring
      only. The induction of sex-specific changes in white matter proteins, in the
      absence of sex differences in thyroxine levels after PCB exposure, suggests that
      serum thyroxine levels do not directly contribute to the white matter
      alterations. Instead, IL-6 may contribute to increased MBP levels in males,
      whereas in females estromimetic and thyromimetic PCB metabolites may affect white
      matter development. This data adds to an increasing body of literature showing
      that perinatal insults induce sex-specific effects in offspring.

PMID- 20691777
TI  - Mutation in erythroid specific transcription factor KLF1 causes Hereditary
      Spherocytosis in the Nan hemolytic anemia mouse model.
AB  - KLF1 regulates definitive erythropoiesis of red blood cells by facilitating
      transcription through high affinity binding to CACCC elements within its
      erythroid specific target genes including those encoding erythrocyte membrane
      skeleton (EMS) proteins. Deficiencies of EMS proteins in humans lead to the
      hemolytic anemia Hereditary Spherocytosis (HS) which includes a subpopulation
      with no known genetic defect. Here we report that a mutation, E339D, in the
      second zinc finger domain of KLF1 is responsible for HS in the mouse model Nan.
      The causative nature of this mutation was verified with an allelic test cross
      between Nan/+ and heterozygous Klf1(+/-) knockout mice. Homology modeling
      predicted Nan KLF1 binds CACCC elements more tightly, suggesting that Nan KLF1 is
      a competitive inhibitor of wild-type KLF1. This is the first association of a
      KLF1 mutation with a disease state in adult mammals and also presents the
      possibility of being another causative gene for HS in humans.

PMID- 20691778
TI  - Sequence analysis and genetic variability of stearoyl CoA desaturase (SCD) gene
      in the Italian Mediterranean river buffalo.
AB  - Stearoyl-CoA desaturase (SCD) plays a key metabolic role by changing the
      saturated FA content of ruminant milk and meat. In this study we characterized
      for the first time the stearoyl-CoA desaturase (SCD) gene in river buffalo
      (Bubalus bubalis) and investigated its genetic variability. On a total of 78
      buffaloes, 15 SNPs were detected and 6 of them were preliminarily genotyped. In
      particular, the g.133A>C SNP was found to create a new consensus site for the SP1
      binding site, thus generating a new tandem repeat in the promoter region. A
      preliminary association study with the milk fatty acid content showed that the C
      allele significantly affects the total desaturation index (P<0.01). Linkage
      disequilibrium analysis allowed identification of 7 haplotypes and 4 tag SNPs.
      Such polymorphisms could represent useful genetic markers for association studies
      with fatty acid composition, but further studies are needed to evaluate their
      potential use to improve the nutritional quality of the dairy products.

PMID- 20691779
TI  - Role of quinones in the ascorbate reduction rates of S-nitrosoglutathione.
AB  - Quinones are one of the largest classes of antitumor agents approved for clinical
      use, and several antitumor quinones are in various stages of clinical and
      preclinical development. Many of these are metabolites of, or are, environmental
      toxins. Because of their chemical structure they are known to enhance electron
      transfer processes such as ascorbate oxidation and NO reduction. The paraquinones
      2,6-dimethyl-1,4-benzoquinone (DMBQ), 1,4-benzoquinone, methyl-1,4-benzoquinone,
      2,6-dimethoxy-1,4-benzoquinone, 2-hydroxymethyl-6-methoxy-1,4-benzoquinone,
      trimethyl-1,4-benzoquinone, tetramethyl-1,4-benzoquinone, and 2,3-dimethoxy-5
      methyl-1,4-benzoquinone; the paranaphthoquinones 1,4-naphthoquinone, menadione,
      1,4-naphthoquinone-2-sulfonate, 2-ethylsulfanyl-3-methyl-1,4-naphthoquinone and
      juglone; and phenanthraquinone (PHQ) all enhance the anaerobic rate of ascorbate
      reduction of GSNO to produce NO and GSH. Rates of this reaction were much larger
      for p-benzoquinones and PHQ than for p-naphthoquinone derivatives with similar
      one-electron redox potentials. The quinone DMBQ also enhances the rate of NO
      production from S-nitrosylated bovine serum albumin upon ascorbate reduction.
      Density functional theory calculations suggest that stronger interactions between
      p-benzo- or phenanthrasemiquinones and GSNO than between p-naphthosemiquinones
      and GSNO are the major causes of these differences. Thus, quinones, and
      especially p-quinones and PHQ, could act as enhancers of NO release from GSNO in
      biomedical systems in the presence of ascorbate. Because quinones are exogenous
      toxins that could enter the human body via a chemotherapeutic application or as
      an environmental contaminant, they could boost the release of NO from S
      nitrosothiol storages in the body in the presence of ascorbate and thus enhance
      the responses elicited by a sudden increase in NO levels.

PMID- 20691780
TI  - Role of oxidative stress in high-glucose- and diabetes-induced increased
      expression of Gq/11alpha proteins and associated signaling in vascular smooth
      muscle cells.
AB  - We have recently shown that aortic vascular smooth muscle cells (VSMCs) from
      streptozotocin (STZ)-induced diabetic rats and A10 VSMCs exposed to high glucose
      exhibited increased levels of Gqalpha and PLCbeta proteins. In the present study,
      we investigated whether the enhanced oxidative stress in hyperglycemia/diabetes
      contributes to the increased expression of the Gq/11alpha and PLCbeta proteins
      and the associated signaling in VSMCs by using antioxidants. The levels of
      Gq/11alpha and PLCbeta1/2 proteins, as determined by Western blotting, were
      significantly increased in A10 VSMCs exposed to high glucose and in aortic VSMCs
      from STZ-diabetic rats compared with control cells and were restored to control
      levels by antioxidants: apocynin, an NADPH oxidase inhibitor, and catalase, a
      scavenger of hydrogen peroxide. However, (111)Mn-tetrakis(benzoic acid porphyrin)
      and uric acid, scavengers of peroxynitrite, did not affect the high-glucose
      induced enhanced levels of Gq/11alpha and PLCbeta proteins in A10 cells.
      Furthermore, the levels of superoxide dismutase-1 (SOD-1) but not of SOD-2
      protein were augmented by high glucose. In addition, high-glucose-induced
      endothelin-1-stimulated production of IP(3) was also restored toward control
      levels by catalase. These results suggest that hyperglycemia/diabetes-induced
      enhanced expression of Gq/11alpha and PLCbeta proteins and signaling may be
      attributable to the enhanced oxidative stress due to augmented levels of H(2)O(2)
      and not to peroxynitrite.

PMID- 20691781
TI  - Dehydroepiandrosterone effects on Akt signaling modulation in central nervous
      system of young and aged healthy rats.
AB  - Dehydroepiandrosterone (DHEA) is a steroid synthesized in adrenal cortex as well
      as in the nervous system. DHEA effects on central nervous system (CNS) have been
      associated with several brain functions such as marked neurotrophic and
      neuroprotective activity. DHEA plasma concentration decreases steadily with aging
      and studies have reported an inverse correlation between levels of DHEA and
      neurological diseases age-associated. Nonetheless, its mechanisms of action are
      not yet fully understood. Akt signaling pathway is one protein kinase which has
      been related to be DHEA modulated. The goal of this study was to investigate
      whether short-term (6 or 24h) or chronic (5 weeks) DHEA treatment modulates Akt
      in CNS of adult (3 months) and aged (18 and 24 months) healthy rats. Hypothalamus
      and hippocampus homogenates were prepared to quantify total-Akt and
      phosphorylated Akt at Ser(473) (pAkt). The results here presented have shown that
      acute (50mg/kg) and chronic (10mg/kg) DHEA injections modulate total and pAkt
      levels. This effect was dose and time-dependent as well as age and tissue
      dependent. In addition, the age variable also intervenes on total and pAkt levels
      expression independently of DHEA treatment.

PMID- 20691782
TI  - Neofunctionalization in an ancestral insect desaturase lineage led to rare Delta6
      pheromone signals in the Chinese tussah silkworm.
AB  - The Chinese tussah silkworm, Antheraea pernyi (Lepidoptera: Saturniidae) produces
      a rare dienoic sex pheromone composed of (E,Z)-6,11-hexadecadienal, (E,Z)-6,11
      hexadecadienyl acetate and (E,Z)-4,9-tetradecadienyl acetate, and for which the
      biosynthetic routes are yet unresolved. By means of gland composition analyses
      and in vivo labeling we evidenced that pheromone biosynthesis towards the
      immediate dienoic gland precursor, the (E,Z)-6,11-hexadecadienoic acid, involves
      desaturation steps with Delta(6) and Delta(11) regioselectivity. cDNA cloning of
      pheromone gland desaturases and heterologous expression in yeast demonstrated
      that the 6,11-dienoic pheromone is generated from two biosynthetic routes
      implicating a Delta(6) and Delta(11) desaturase duo albeit with an inverted
      reaction order. The two desaturases first catalyze the formation of the (E)-6
      hexadecenoic acid or (Z)-11-hexadecenoic acid, key mono-unsaturated biosynthetic
      intermediates. Subsequently, each enzyme is able to produce the (E,Z)-6,11
      hexadecadienoic acid by accommodating its non-respective mono-unsaturated
      product. Besides elucidating an unusually flexible pheromone biosynthetic
      pathway, our data provide the first identification of a biosynthetic Delta(6)
      desaturase involved in insect mate communication. The occurrence of this novel
      Delta(6) desaturase function is consistent with an evolutionary scenario
      involving neo-functionalization of an ancestral desaturase belonging to a gene
      lineage different from the Delta(11) desaturases commonly involved in moth
      pheromone biosynthesis.

PMID- 20691783
TI  - The catalytic and other residues essential for the activity of the midgut
      trehalase from Spodoptera frugiperda.
AB  - Trehalase (EC 3.2.1.28) hydrolyzes only alpha, alpha'- trehalose and is present
      in a variety of organisms, but is most important in insects and fungi.
      Crystallographic data showed that bacterial trehalase has D312 and E496 as the
      catalytical residues and three Arg residues in the active site. Those residues
      have homologous in all family 37 trehalases including Spodoptera frugiperda
      trehalase (D322, E520, R169, R227, R287). To test the role of these residues,
      mutants of trehalase were produced. All mutants were at least four orders of
      magnitude less active than wild type trehalase and no structural difference
      between these mutants and wild type enzyme were discernible by circular
      dichroism. D322A and E520 pH-activity profile lacked the alkaline arm and the
      acid arm, respectively, suggesting that D322 is the acid and E520 the basic
      catalyst. Azide increases E520A activity three times, confirming its action as
      the basic catalyst. Taking into account the decrease in activity after
      substitution for alanine residue, the three arginine residues are as important as
      the catalytical ones to trehalase activity. This clarifies the previous
      misidentification of an Arg residue as the acid catalyst. As far as we know, this
      is the first report on the functional identification residues important for
      trehalase activity.

PMID- 20691784
TI  - Phenol-oxidizing laccases from the termite gut.
AB  - cDNAs encoding two gut laccase isoforms (RfLacA and RfLacB) were sequenced from
      the termite Reticulitermes flavipes. Phylogenetic analyses comparing translated
      R. flavipes laccases to 67 others from prokaryotes and eukaryotes indicate that
      the R. flavipes laccases are evolutionarily unique. Alignments with
      crystallography-verified laccases confirmed that peptide motifs involved in metal
      binding are 100% conserved in both isoforms. Laccase transcripts and
      phenoloxidase activity were most abundant in symbiont-free salivary gland and
      foregut tissue, verifying that the genes and activities are host-derived. Using a
      baculovirus-insect expression system, the two isoforms were functionally
      expressed with histidine tags and purified to near homogeneity. ICP-MS
      (inductively coupled plasma - mass spectrometry) analysis of RfLacA identified
      bound metals consisting mainly of copper (~4 copper molecules per laccase protein
      molecule and ~3 per histidine tag) with lesser amounts of calcium, manganese and
      zinc. Both recombinant enzyme preparations showed strong activity towards the
      lignin monomer sinapinic acid and four other phenolic substrates. By contrast,
      both isoforms displayed much lower or no activity against four melanin
      precursors, suggesting that neither isoform is involved in integument formation.
      Modification of lignin alkali by the recombinant RfLacA preparation was also
      observed. These findings provide evidence that R. flavipes gut laccases are
      evolutionarily distinct, host-derived, produced in the salivary gland, secreted
      into the foregut, bind copper, and play a role in lignocellulose digestion. These
      findings contribute to a better understanding of termite digestion and gut
      physiology, and will assist future translational studies that examine the
      contributions of individual termite enzymes in lignocellulose digestion.

PMID- 20691785
TI  - Characterization and kinetic analysis of protein tyrosine phosphatase-H2 from
      Microplitis demolitor bracovirus.
AB  - The polydnavirus Microplitis demolitor bracovirus (MdBV) encodes 13 genes that
      share homology with classical protein tyrosine phosphatases (PTPs). Prior
      sequence analysis suggested that five members of the MdBV PTP gene family (ptp
      H2, -H3, -H5, -N1 and -N2) encode PTPs, seven family members encode
      pseudophosphatases, and one family member is a pseudogene. Prior experimental
      studies further implicated PTP-H2 in disabling the function of host hemocytes
      following infection by MdBV. Here we report expression of PTP-H2 and selected
      mutants in Escherichia coli cells as non-fusion or thioredoxin-fusion proteins.
      Following purification by nickel affinity chromatography, the full-length and
      mutant proteins ran as single bands of predicted size on SDS-PAGE gels under
      reducing conditions. The non-fusion form of PTP-H2 exhibited classical Michaelis
      Menten kinetics using the phosphopeptide END(pY)INASL and difluoro-4
      methylumbiliferyl phosphate (DiFMUP) as substrates. As expected, the non-fusion
      mutant PTP-H2(C236S) had no enzymatic activity, while the thioredoxin-fusion form
      of PTP-H2 had low levels of activity. PTP-H2 exhibited optimal activity at pH 4.0
      and 26 degrees C in sodium acetate buffer, and its activity was diminished by
      increasing buffer ionic strength. Activity was also greatly reduced by the
      presence of copper, heparin, and the classical PTP inhibitor vanadate. Using an
      anti-PTP-H2 antibody, immunoblotting and immunocytochemical studies only detected
      PTP-H2 in hemocytes from MdBV-infected Pseudoplusia includens. Overall, our
      results indicate that PTP-H2 is a functional tyrosine phosphatase that is
      specifically expressed in MdBV-infected hemocytes.

PMID- 20691787
TI  - Sub-chronic exposure to atomoxetine up-regulates BDNF expression and signalling
      in the brain of adolescent spontaneously hypertensive rats: comparison with
      methylphenidate.
AB  - The stimulant methylphenidate and the non-stimulant atomoxetine are widely used
      for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD), but the
      molecular mechanisms of their therapeutic action are not fully understood. The
      aim of our study was to investigate, in adolescent rats, the sub-chronic effect
      of these two drugs on neuronal plasticity, through a detailed analysis of BDNF
      expression and signalling in order to establish the contribution of these
      mechanisms in the pharmacotherapy of ADHD. Atomoxetine (ATX) up-regulated BDNF
      mRNA levels in the hippocampus whereas methylphenidate (MPH) increased BDNF gene
      expression in the nucleus accumbens and caudate-putamen. Opposite effects were
      seen in the prefrontal cortex, a critical region in attention disorders, where
      ATX increased while MPH reduced total and exon IV BDNF mRNA levels. Analysis of
      BDNF-mediated signalling in the prefrontal cortex revealed that ATX enhanced AKT
      and GSK3beta phosphorylation whereas MPH reduced the synaptic levels of trkB, the
      high-affinity BDNF receptor, and ERK1/2 activation. Our findings show that ATX
      and MPH exert an opposite modulation of the BDNF system, primarily in prefrontal
      cortex that, independently from the behavioral control exerted by the two drugs,
      may be important for long-term consequences on cognitive function.

PMID- 20691786
TI  - Increased coupling and altered glutamate transport currents in astrocytes
      following kainic-acid-induced status epilepticus.
AB  - Profound astrogliosis coincident with neuronal cell loss is universally described
      in human and animal models of temporal lobe epilepsy (TLE). In the kainic acid
      induced status epilepticus (SE) model of TLE, astrocytes in the hippocampus
      become reactive soon after SE and before the onset of spontaneous seizures. To
      determine if astrocytes in the hippocampus exhibit changes in function soon after
      SE, we recorded from SR101-labeled astrocytes using the whole-cell patch
      technique in hippocampal brain slices prepared from control and kainic-acid
      treated rats. Glutamate transporter-dependent currents were found to have
      significantly faster decay time kinetics and in addition, dye coupling between
      astrocytes was substantially increased. Consistent with an increase in dye
      coupling in reactive astrocytes, immunoblot experiments demonstrated a
      significant increase in both glial fibrillary acidic protein (GFAP) and connexin
      43, a major gap junction protein expressed by astrocytes. In contrast to what has
      been observed in resected tissue from patients with refractory epilepsy, changes
      in potassium currents were not observed shortly after KA-induced SE. While many
      changes in neuronal function have been identified during the initial period of
      low seizure probability in this model of TLE, the present study contributes to
      the growing body of literature suggesting a role for astrocytes in the process of
      epileptogenesis.

PMID- 20691788
TI  - On the evolutionary origins of "Fold Space Continuity": a study of topological
      convergence and divergence in mixed alpha-beta domains.
AB  - Existing protein structure classifications group proteins by overall structural
      similarity at the highest level and by evolutionary relationships at the lowest
      level, deriving higher-level groups by pairwise structure comparison. For this to
      be successful requires that large changes in structure are relatively rare in
      evolution and that proteins with no detectable evolutionary relationship do not
      converge on similar global chain conformations since this creates conflicts
      between structural and evolutionary consistency. Analysis of global structural
      changes using core topological descriptions for 4261 domains from classes C and D
      of the SCOP database and new measures of topological distance and consistency of
      classification showed that the topological consistency of SCOP folds is highly
      variable with some folds having no consistent description and significant
      overlaps between groups including some members of separate folds with identical
      topological descriptions. Topological clustering shows that including sufficient
      indels to allow family members to be joined would also require joining several
      distinct folds. We conclude that evolutionary changes in the global topology of
      protein domains are the root cause of many difficulties for present approaches to
      structure classification using pairwise comparison. As a resolution we propose
      that a purely structural classification should be created using an approach
      similar to that adopted by the Gene Ontology in which proteins are assigned
      labels describing structure.

PMID- 20691789
TI  - Characterization of myosin light chain in shrimp hemocytic phagocytosis.
AB  - Myosin light chain, a well-known cytoskeleton gene, regulates multiple processes
      that are involved in material transport, muscle shrink and cell division.
      However, its function in phagocytosis against invading pathogens in crustacean
      remains unknown. In this investigation, a myosin light chain gene was obtained
      from Marsupenaeus japonicus shrimp. The full-length cDNA of this gene was of 766
      bp and an open reading frame (ORF) of 462 bp encoding a polypeptide of 153 amino
      acids. The myosin light chain protein was expressed in Escherichia coli and
      purified. Subsequently the specific antibody was raised using the purified GST
      fusion protein. As revealed by immuno-electron microscopy, the myosin light chain
      protein was only expressed in the dark bands of muscle. In the present study, the
      myosin light chain gene was up-regulated in the WSSV-resistant shrimp as revealed
      by real-time PCR and western blot. And the phagocytic percentage and phagocytic
      index using FITC-labeled Vibrio parahemolyticus were remarkably increased in the
      WSSV-resistant shrimp, suggesting that the myosin light chain protein was
      essential in hemocytic phagocytosis. On the other hand, RNAi assays indicated
      that the phagocytic percentage and phagocytic index were significantly decreased
      when the myosin light chain gene was silenced by sequence-specific siRNA. These
      findings suggested that myosin light chain protein was involved in the regulation
      of hemocytic phagocytosis of shrimp.

PMID- 20691790
TI  - Encoding and decoding in fMRI.
AB  - Over the past decade fMRI researchers have developed increasingly sensitive
      techniques for analyzing the information represented in BOLD activity. The most
      popular of these techniques is linear classification, a simple technique for
      decoding information about experimental stimuli or tasks from patterns of
      activity across an array of voxels. A more recent development is the voxel-based
      encoding model, which describes the information about the stimulus or task that
      is represented in the activity of single voxels. Encoding and decoding are
      complementary operations: encoding uses stimuli to predict activity while
      decoding uses activity to predict information about the stimuli. However, in
      practice these two operations are often confused, and their respective strengths
      and weaknesses have not been made clear. Here we use the concept of a linearizing
      feature space to clarify the relationship between encoding and decoding. We show
      that encoding and decoding operations can both be used to investigate some of the
      most common questions about how information is represented in the brain. However,
      focusing on encoding models offers two important advantages over decoding. First,
      an encoding model can in principle provide a complete functional description of a
      region of interest, while a decoding model can provide only a partial
      description. Second, while it is straightforward to derive an optimal decoding
      model from an encoding model it is much more difficult to derive an encoding
      model from a decoding model. We propose a systematic modeling approach that
      begins by estimating an encoding model for every voxel in a scan and ends by
      using the estimated encoding models to perform decoding.

PMID- 20691791
TI  - Spatio-temporal brain dynamics in a combined stimulus-stimulus and stimulus
      response conflict task.
AB  - It is yet not well known whether different types of conflicts share common or
      rely on distinct brain mechanisms of conflict processing. We used a combined
      Flanker (stimulus-stimulus; S-S) and Simon (stimulus-response; S-R) conflict
      paradigm both in an fMRI and an EEG study. S-S conflicts induced stronger
      behavioral interference effects compared to S-R conflicts and the latter decayed
      with increasing response latencies. Besides some similar medial frontal activity
      across all conflict trials, which was, however, not statically consistent across
      trials, we especially found distinct activations depending on the type of
      conflict. S-S conflicts activated the anterior cingulate cortex and modulated the
      N2 and early P3 component with underlying source activity in inferior frontal
      cortex. S-R conflicts produced distinct activations in the posterior cingulate
      cortex and modulated the late P3b component with underlying source activity in
      superior parietal cortex. Double conflict trials containing both S-S and S-R
      conflicts revealed, first, distinct anterior frontal activity representing a meta
      processing unit and, second, a sequential modulation of the N2 and the P3b
      component. The N2 modulation during double conflict trials was accompanied by
      increased source activity in the medial frontal gyrus (MeFG). In summary, S-S and
      S-R conflict processing mostly rely on distinct mechanisms of conflict processing
      and these conflicts differentially modulate the temporal stages of stimulus
      processing.

PMID- 20691793
TI  - BA3b and BA1 activate in a serial fashion after median nerve stimulation: direct
      evidence from combining source analysis of evoked fields and cytoarchitectonic
      probabilistic maps.
AB  - This study combines source analysis imaging data for early somatosensory
      processing and the probabilistic cytoarchitectonic maps (PCMs). Human
      somatosensory evoked fields (SEFs) were recorded by stimulating left and right
      median nerves. Filtering the recorded responses in different frequency ranges
      identified the most responsive frequency band. The short-latency averaged SEFs
      were analyzed using a single equivalent current dipole (ECD) model and magnetic
      field tomography (MFT). The identified foci of activity were superimposed with
      PCMs. Two major components of opposite polarity were prominent around 21 and 31
      ms. A weak component around 25 ms was also identified. For the most responsive
      frequency band (50-150 Hz) ECD and MFT revealed one focal source at the
      contralateral Brodmann area 3b (BA3b) at the peak of N20. The component ~25 ms
      was localised in Brodmann area 1 (BA1) in 50-150 Hz. By using ECD, focal
      generators around 28-30 ms located initially in BA3b and 2 ms later to BA1. MFT
      also revealed two focal sources - one in BA3b and one in BA1 for these latencies.
      Our results provide direct evidence that the earliest cortical response after
      median nerve stimulation is generated within the contralateral BA3b. BA1
      activation few milliseconds later indicates a serial mode of somatosensory
      processing within cytoarchitectonic SI subdivisions. Analysis of non-invasive
      magnetoencephalography (MEG) data and the use of PCMs allow unambiguous and
      quantitative (probabilistic) interpretation of cytoarchitectonic identity of
      activated areas following median nerve stimulation, even with the simple ECD
      model, but only when the model fits the data extremely well.

PMID- 20691792
TI  - Interactive effects of physical activity and APOE-epsilon4 on BOLD semantic
      memory activation in healthy elders.
AB  - Evidence suggests that physical activity (PA) is associated with the maintenance
      of cognitive function across the lifespan. In contrast, the apolipoproteinE
      epsilon4 (APOE-epsilon4) allele, a genetic risk factor for Alzheimer's disease
      (AD), is associated with impaired cognitive function. The objective of this study
      was to examine the interactive effects of PA and APOE-epsilon4 on brain
      activation during memory processing in older (ages 65-85) cognitively intact
      adults. A cross-sectional design was used with four groups (n=17 each): (1) Low
      Risk/Low PA; (2) Low Risk/High PA; (3) High Risk/Low PA; and (4) High Risk/High
      PA. PA level was based on self-reported frequency and intensity. AD risk was
      based on presence or absence of an APOE-epsilon4 allele. Brain activation was
      measured using event-related functional magnetic resonance imaging (fMRI) while
      participants performed a famous name discrimination task. Brain activation
      subserving semantic memory processing occurred in 15 functional regions of
      interest. High PA and High Risk were associated with significantly greater
      semantic memory activation (famous>unfamiliar) in 6 and 3 of the 15 regions,
      respectively. Significant interactions of PA and Risk were evident in 9 of 15
      brain regions, with the High PA/High Risk group demonstrating greater semantic
      memory activation than the remaining three groups. These findings suggest that PA
      selectively increases memory-related brain activation in cognitively intact but
      genetically at-risk elders. Longitudinal studies are required to determine
      whether increased semantic memory processing in physically active at-risk
      individuals is protective against future cognitive decline.

PMID- 20691794
TI  - Processing of infant-directed speech by adults.
AB  - Adults typically address infants in a special speech mode called infant-directed
      speech (IDS). IDS is characterized by a special prosody (i.e., higher pitched,
      slower and hyperarticulated) and a special lexicon ("baby talk"). Here we
      investigated which areas of the adult brain are involved in processing IDS, which
      aspects of IDS (prosodic or lexical) are processed, to what extent the experience
      of being a parent affects the way adults process IDS, and the effects of gender
      and personality on IDS processing. Using functional magnetic resonance imaging,
      we found that mothers with preverbal infants showed enhanced activation in the
      auditory dorsal pathway of the language areas, regardless of whether they
      listened to the prosodic or lexical component of IDS. We also found that
      extroverted mothers showed higher cortical activation in speech-related motor
      areas than did mothers with lower extroverted personality scores. Increased
      cortical activation levels were not found for fathers, non-parents, or mothers
      with older children.

PMID- 20691795
TI  - Treatment with TNF-alpha inhibitor infliximab might reduce hand osteoarthritis in
      patients with rheumatoid arthritis.
AB  - OBJECTIVES: To investigate the association between systemic and local
      inflammation and incident and progressive radiographic secondary osteoarthritis
      (OA) in interphalangeal joints (IPJs) over 3 years in rheumatoid arthritis (RA)
      patients and the effect of tumor necrosis factor alpha (TNF-alpha) inhibitor
      infliximab on secondary OA in IPJs. METHODS: In the present observational
      longitudinal study baseline and 3-year hand X-rays of 416 recent-onset RA
      patients were scored for osteophytes and erosions in IPJs, blinded for time,
      using Osteoarthritis Research Society International atlas and Sharp-van der
      Heijde score. The associations between inflammatory factors and incident and
      progressive secondary OA in distal IPJs (DIPJs) and proximal IPJs (PIPJs) and the
      effect of infliximab compared to disease-modifying anti-rheumatic drug treatment
      on secondary OA were analyzed by multivariable regression and generalised
      estimating equations analyses. RESULTS: Sixty-seven percent of the patients were
      female with, at baseline, a mean age of 54 years and OA present in DIPJs and
      PIPJs in 37% and 13%. Three years later, new secondary OA in DIPJs and PIPJs was
      seen in 11% and 10%, and progressive secondary OA in 36% and 35%. High
      erythrocyte sedimentation rate over 3 years and progressive erosive damage were
      risk factors for incident secondary OA in DIPJs, but not in PIPJs. At joint
      level, progression of erosions was associated with both incident and progressive
      secondary OA, only in DIPJs. Infliximab treatment was associated with lower
      incident secondary OA in PIPJs [relative risk 0.5 (95% confidence interval 0.2,
      1.0)], independent of decrease in inflammation. CONCLUSION: Incident and
      progressive secondary OA in DIPJs over 3 years was associated with high
      inflammatory activity in RA. Infliximab treatment reduced incident secondary OA
      in PIPJs independent of decrease in inflammation, suggesting that anti-TNF-alpha
      therapy might be effective against secondary hand OA via other pathways than
      suppression of inflammation. Further studies in populations of primary hand OA
      are necessary to determine the role of anti-TNF-alpha in treatment of primary
      hand OA.

PMID- 20691796
TI  - Anatomical distribution of synovitis in knee osteoarthritis and its association
      with joint effusion assessed on non-enhanced and contrast-enhanced MRI.
AB  - PURPOSE: To describe the anatomical distribution of synovitis and its association
      with joint effusion on non-enhanced and contrast-enhanced (CE) MRI in patients
      with knee osteoarthritis (OA). METHODS: Baseline MRI was performed at 1.5T using
      axial proton density (PD)-weighted (w) fat suppressed (fs) and axial and sagittal
      T1-w fs CE sequences. Synovial enhancement was scored in nine articular
      subregions. Maximum synovial enhancement was grouped as absent (0), equivocal (1)
      and definite (2 and 3). Effusion was scored from 0 to 3 on the axial sequences.
      We described the anatomical distribution of synovitis, its association with
      effusion and compared assessment of effusion on T1-w fs CE and PD fs sequences.
      RESULTS: 111 subjects were included and examined by MRI. 89.2% of knees exhibited
      at least one subregion with a minimum grade 2 and 39.6% at the maximum of a grade
      3. The commonest sites for definite synovitis were posterior to the posterior
      cruciate ligament (PCL) in 71.2% and in the suprapatellar region in 59.5% of all
      knees. On T1-w fs CE, 73.0% of knees showed any effusion. Definite synovitis in
      at least one location was present in 96.3% knees with an effusion and in 70.0%
      without an effusion. Higher grades of effusion were scored on the PD fs sequence.
      CONCLUSION: Definite synovitis was present in the majority of knees with or
      without effusion with the commonest sites being posterior to the PCL and in the
      suprapatellar recess. Joint effusion as measured on PD fs images does not only
      represent effusion but also synovial thickening.

PMID- 20691797
TI  - Association of single-nucleotide polymorphisms in HLA class II/III region with
      knee osteoarthritis.
AB  - OBJECTIVE: A genome-wide association study and a replication using Japanese,
      Spanish and Greek Caucasian populations have recently indicated two single
      nucleotide polymorphisms (SNPs) (rs7775228 and rs10947262) associated with knee
      Osteoarthritis (OA) susceptibility. We have further evaluated the association in
      knee OA subjects from Han Chinese and Australian Caucasian origin. METHODS: Two
      independent case-control association studies were performed using Han Chinese and
      Australian Caucasian populations. The two SNPs were genotyped in patients who had
      primary symptomatic knee OA with radiographic confirmation and/or received total
      knee replacement surgery as well as in matched controls. They were subjected to
      statistic analyses. RESULTS: A total of 991 OA patients and 1536 controls were
      genotyped. No significant difference was detected in genotype or allele
      frequencies of the two SNPs between knee OA and control groups in the two
      populations (all P>0.05). The association was also negative even after
      stratification by sex, body mass index (BMI) and Kellgren/Lawrence scores. The
      significant heterogeneity was detected between Chinese and Japanese (both
      P<0.05). In the Caucasian samples, no significant heterogeneity was detected
      (both P>0.05). The result of meta-analysis showed significant association between
      knee OA and rs10947262 in total subjects [summary OR=1.26, 95%confidence
      intervals (CI)=1.07-1.27, P=3 * 10(-8)] and in Caucasian samples (summary
      OR=1.28, 95%CI=1.04-1.57, P=0.02). CONCLUSION: We demonstrated no association
      between the two SNPs in human leukocyte antigen (HLA) class II/III region and
      knee OA in Han Chinese population. A significant association was detected between
      SNP rs10947262 and knee OA in Caucasian subjects. Further replication studies are
      required to identify the impact of controversial association.

PMID- 20691798
TI  - Reference values and Z-scores for subregional femorotibial cartilage thickness-
      results from a large population-based sample (Framingham) and comparison with the
      non-exposed Osteoarthritis Initiative reference cohort.
AB  - OBJECTIVE: To establish sex-specific (subregional) reference values of cartilage
      thickness and potential maximal Z-scores in the femorotibial joint. METHODS: The
      mean cartilage thickness (ThCtAB.Me) in femorotibial compartments, plates and
      subregions was determined on coronal magnetic resonance imaging (MRI) from a
      population-based sample (Framingham) and from a healthy reference sample of the
      Osteoarthritis Initiative (OAI). RESULTS: 686 Framingham participants (309 men,
      377 women, age 62 +/- 8 years) had no radiographic femorotibial osteoarthritis
      (OA) ("normals") and 376 (156 men, 220 women) additionally had no MRI features of
      cartilage lesions ("supernormals"). The Framingham "normals" had thinner
      cartilage in the medial (3.59 mm) than in the lateral femorotibial compartment
      (3.86 mm). Medially, the femur displayed thicker cartilage (1.86 mm) than the
      tibia (1.73 mm), and laterally the tibia thicker cartilage (2.09 mm) than the
      femur (1.77 mm). The thickest cartilage was observed in central, and the thinnest
      in external femorotibial subregions. Potential maximal Z-scores ranged from 5.6
      to 9.8 throughout the subregions; men displayed thicker cartilage but similar
      potential maximal Z-scores as women. Mean values and potential maximal Z-scores
      in Framingham "supernormals" and non-exposed OAI reference participants (112
      participants without symptoms or risk factors of knee OA) were similar to
      Framingham "normals". CONCLUSIONS: We provide reference values and potential
      maximal Z-scores of cartilage thickness in middle aged to elderly non-diseased
      populations without radiographic OA. Results were similar for "supernormal"
      participants without MRI features of cartilage lesions, and in a cohort without
      OA symptoms or risk factors. A cartilage thickness loss of around 27% is required
      for attaining a Z-score of -2.

PMID- 20691799
TI  - Regulatory T cell content in the bone marrow graft does not predict the
      occurrence of acute GVHD.
AB  - The subpopulation of regulatory T cells (Treg) was shown to play a key role in
      alloreactive responses. In allogeneic hematopoietic stem cell transplantation,
      several groups tested whether Treg content in transplants correlates with graft
      versus-host disease (GVHD) with controversial results. In a retrospective study
      of 49 consecutive HLA-matched sibling transplantations, we studied the
      relationship between Treg content in bone marrow transplants and acute GVHD
      (aGVHD) occurrence. We observed a large variability in Treg in bone marrow
      grafts. However, contrary to previous observations in peripheral blood stem cells
      transplantation, we report that the Treg content of allogeneic bone marrow
      transplantation did not predict the occurrence of aGVHD.

PMID- 20691800
TI  - Individualized intervention guided by BCR-ABL transcript levels after HLA
      identical sibling donor transplantation improves HSCT outcomes for patients with
      chronic myeloid leukemia.
AB  - The aim of this study was to determine the effect of individualized intervention
      guided by BCR-ABL transcript levels after hematopoietic stem cell transplantation
      (HSCT) on relapse and leukemia-free survival (LFS) of patients with chronic
      myelogenous leukemia (CML). Eighty-four consecutive patients who received HLA
      identical sibling HSCT were enrolled. The patients were conditioned with a
      modified busulfan and cyclophosphamide regimen, and received stem cells from a
      HLA-identical sibling donor. Patients were identified as high risk of relapse
      based on serial monitoring of post-HSCT BCR-ABL transcript levels, and patients
      in the high-risk group were given individualized intervention. Interventions
      included immunosuppressant withdrawal, modified donor lymphocyte infusion, and
      imatinib mesylate. Engraftment was successful in all patients. Twenty-eight
      patients were categorized as high risk because of higher post-HSCT BCR-ABL
      transcript levels and received intervention. The 56 low-risk patients received no
      intervention. Twenty-five high-risk patients achieved complete molecular
      remission at a median of 49 days (range: 18-232 days) after intervention. Two
      high-risk patients and 1 low-risk patient ultimately relapsed, the 4-year relapse
      rate was 3.9% +/- 4.4%. Overall 4-year survival was 89.0% +/- 7% and the 4-year
      LFS was 89.2% +/- 6.8%. All surviving patients remains in complete molecular
      remission after a median of 1481 (1040-1794) days follow-up. Individualized
      intervention based on the post-HSCT BCR-ABL transcript level can decrease relapse
      and increase LFS of patients with CML after HLA-identical sibling HSCT.

PMID- 20691801
TI  - Diagnosis and staging of chronic graft-versus-host disease in the clinical
      practice.
AB  - Based on expert opinion and retrospective data the National Institutes of Health
      (NIH) Consensus Development Project proposed criteria for diagnosis and staging
      of both overall severity as well as organ severity of chronic graft-versus-host
      disease (cGVHD) for use in clinical trials. In 2008, representatives of German
      and Austrian allogeneic hematopoietic stem cell transplant (HSCT) centers
      established a study group on cGVHD during the annual meeting of the German
      Working Group on Bone Marrow and Blood Stem Cell Transplantation (DAG-KBT) to
      intensify a dialog among HSCT physicians, pathologists, and medical consultants
      focusing on the usefulness of the NIH consensus criteria for patient care in
      clinical practice and to promote collaborations between HSCT centers as well as
      different medical specialities involved in HSCT. We first conducted a survey of
      current practices of diagnosis, staging, and overall grading of cGVHD in daily
      clinical routine by sending an electronic questionnaire to the heads of the HSCT
      centers. During 3 meetings in 2009, more representatives of allogeneic HSCT
      centers were included into the discussion process, resulting in 81% participation
      representing 88% of all allogeneic HSCT activities in Germany, Austria, and
      Switzerland. During the third consensus meeting held in Regensburg, Germany, from
      November 6 to November 7, 2009, important agreements were achieved among
      participant having a strong impact on care of patients with cGVHD. Areas of
      disagreement such as distinction between classical NIH cGVHD and overlap syndrome
      or assignment of liver GVHD after day 100 to acute or chronic category will be
      further assessed in prospective observational studies among participants in the
      near future.

PMID- 20691802
TI  - [Epidemiology of fungaemia in a paediatric hospital of high complexity].
AB  - BACKGROUND: A retrospective study on the epidemiology of fungaemia due to yeasts
      of medical importance at the Hospital Nacional de Pediatria Prof. Dr. J.
      Garrahan, Buenos Aires was conducted between September 2001 and September 2003.
      OBJECTIVES: To learn the distribution of yeast species and to evaluate their in
      vitro antifungal susceptibility profile. METHODS: The minimum inhibitory
      concentration (MIC) was determined according to the CLSI M27-A2 procedure, and
      time kill curves against amphotericin B were also performed. RESULTS-CONCLUSIONS:
      The species isolated were Candida parapsilosis (32.6% of isolates); Candida
      albicans (26.5%), Candida tropicalis (24.5%), and other yeasts (16.4%). Candida
      isolates were susceptible to the antifungals evaluated, but amphotericin B
      tolerant isolates were detected using time kill curves.

PMID- 20691803
TI  - Does inflammatory acne result from imbalance in the keratinocyte innate immune
      response?
AB  - Acne is a multifactorial chronic disease affecting around 80% of teenage
      population. The pathogenesis of acne involves inflammatory reactions and
      colonization by the Propionibacterium acnes (P. acnes) strain. P. acnes
      stimulates the keratinocytes involved in the innate immune response, the
      intensity of which could be influenced either by bacterial intrinsic factors or
      by endogenous factors of the host.

PMID- 20691804
TI  - Histopathologic and immunologic effects of the itraconazole treatment in a murine
      model of chronic pulmonary paracoccidioidomycosis.
AB  - A comparative study, based on histopathologic findings (inflammation,
      cellularity, and fibrosis) and immunologic parameters (pro-inflammatory and anti
      inflammatory cytokines), was carried out in order to evaluate the effects of
      itraconazole (ITC) treatment and its starting time in a BALB/c murine model of
      chronic pulmonary paracoccidioidomycosis (PCM), induced by intranasal inoculation
      of Paracoccidioides brasiliensis (Pb) conidia. Two different groups of mice were
      exposed to ITC therapy beginning at the 4th or 8th week after Pb infection,
      respectively. ITC was administered daily, via gavage, for a period of sixty days.
      At weeks 0, 4, 8, 12 and 16 the animals were sacrificed and their lungs removed
      for histology staining with hematoxylin and eosin (H&E), Masson's trichromic and
      Gomori-Grocott; pulmonary levels of IL-1beta, TNF-alpha, IFN-gamma, IL-13 and TGF
      beta were also measured by ELISA. The development or absence of the principal
      pulmonary PCM sequela, lung fibrosis, was directly related to the therapy's
      starting time. This and other histopathologic findings were related to the
      behavior of cytokine levels.

PMID- 20691806
TI  - Sodium butyrate down-regulation of indoleamine 2, 3-dioxygenase at the
      transcriptional and post-transcriptional levels.
AB  - The clinical outcomes of most immunotherapeutic strategies have been less
      effective than anticipated partially because of the tumor immune tolerance
      induced by many immune tolerance factors, which originate from the tumor and
      tumor microenvironment. Indoleamine 2, 3-dioxygenase (IDO) is an interferon-gamma
      (IFN-gamma)-inducible enzyme and is one of main immune tolerance factors during
      tumor development. Sodium butyrate (NaB) has received much attention as a
      potential chemopreventive agent for cancer treatment due to its protective action
      against intracellular events including IFN-gamma-mediated signaling transduction.
      Therefore, the question remains whether IDO is a target of the anti-tumor action
      of NaB. In this study, we demonstrate for the first time that NaB down-regulated
      IDO via both transcriptional and post-transcriptional mechanisms. NaB repressed
      the activity of STAT1 to inhibit STAT1-driven transcriptional activity of IDO.
      These mechanisms included inhibiting STAT1 701 tyrosine phosphorylation, nuclear
      translocation, and repression of STAT1 binding to gamma-activated sites (GAS).
      Moreover, immunoprecipitation and immunoblotting assays showed that treatment of
      cells with NaB caused dramatic ubiquitination of total intracellular proteins,
      including IDO. Blocking 26S proteasome activity by addition of its specific
      inhibitor, bortezomib, reversed the ubiquitination and down-regulation of IDO.
      These results suggest that NaB-induced STAT1 activity inhibition and
      ubiquitin/proteasome-dependent proteolysis are involved in the down-regulation of
      IDO. The discoveries in this study represent a new mechanism in the anti-tumor
      action of NaB and may have implications for development of clinical cancer
      immunotherapy.

PMID- 20691805
TI  - Is Mycobacterium tuberculosis stressed out? A critical assessment of the genetic
      evidence.
AB  - Mycobacterium tuberculosis is an obligate human intracellular pathogen which
      remains a major killer worldwide. A remarkable feature of M. tuberculosis
      infection is the ability of the pathogen to persist within the host for decades
      despite an impressive onslaught of stresses. In this review we seek to outline
      the host-inflicted stresses experienced by M. tuberculosis, the bacterial
      strategies used to withstand these stresses, and how this information should
      guide our efforts to combat this global pathogen.

PMID- 20691807
TI  - The human papillomavirus-16 (HPV-16) oncoprotein E7 conjugates with and mediates
      the role of the transforming growth factor-beta inducible early gene 1 (TIEG1) in
      apoptosis.
AB  - The human papillomavirus (HPV) oncoprotein E7 is a major transforming protein.
      The E7 protein does not possess intrinsic enzymatic activity, but rather
      functions through direct and indirect interactions with cellular proteins,
      several of which are well known cellular tumor suppressors. Using the yeast two
      hybrid system, we found that transforming growth factor-beta inducible early gene
      1 (TIEG1), a member of the Kruppel-like family (KLF) that has been implicated as
      a putative tumor suppressor, interacts and forms a specific complex with HPV-16
      E7. TIEG1 has been shown to mimic the effects of TGF-beta in various carcinoma
      cells and plays a critical role in the apoptotic cascade. Our results indicate
      that E7 binds to the C-terminus of TIEG1 and induces its degradation via the
      ubiquitin pathway. E7 not only increased the ubiquitination of TIEG1 but also
      influenced the ability of TIEG1 to affect apoptosis. Our results suggest that
      suppression of TIEG1-mediated signaling by E7 may contribute to HPV-associated
      carcinogenesis.

PMID- 20691808
TI  - The novel protein BboRhop68 is expressed by intraerythrocytic stages of Babesia
      bovis.
AB  - The apical complex of intracellular hemoparasites contains organelles like
      micronemes and rhoptries, specialized structures required for adherence and
      invasion of host cells. Several molecules discharged from rhoptries have been
      identified from Plasmodium spp., but only a single rhoptry associated protein-1
      (RAP-1) has been characterized from Babesia bovis. In silico search of the B.
      bovis genome allowed to identifying a sequence homologous to the gene that
      encodes a P. falciparum rhoptry protein PfRhop148. The intron-less 1830 bp novel
      gene, predicted a 68kDa protein, and it was highly conserved among different B.
      bovis strains and isolates. The deducted protein from the B. bovis T2Bo strain,
      named BboRhop68, showed two putative transmembrane domains, at least seven B-cell
      epitopes, and a well conserved DUF501 super family domain. The bborhop68 gene was
      amplified, analyzed and compared among different B. bovis strains and isolates
      showing overall high sequence conservation. A fragment of bborhop68 was expressed
      as a recombinant fusion protein (rBboRhop68). The mice anti-rBboRhop68 serum
      identified the novel protein in intraerythrocytic trophozoites and merozoites by
      WB and ELISA, but not in free merozoites. Sera from naturally and experimentally
      infected bovines also recognized BboRhop68, suggesting that it is expressed and
      immunogenic during B. bovis infection. Fluorescence microscopy analysis using
      anti-rBboRhop68 antibodies showed a rod structure associated to trophozoites and
      merozoites infected erythrocytes, but this pattern of reactivity was not observed
      in free merozoites. The BboRhop68 was also not detected in ELISA based on
      solubilized merozoites. Thus, at least three independent lines of evidence
      support differential expression of BboRhop68 in intraerythrocytic stages of B.
      bovis and its possible functional role immediately after B. bovis erythrocyte
      invasion. The results of this work suggest that BboRhop68 could be considered as
      a novel additional target for developing improved methods to control bovine
      babesiosis.

PMID- 20691809
TI  - Molecular detection of Cryptosporidium cuniculus in rabbits in Australia.
AB  - In the United Kingdom, rabbits have been reported to harbour genotypes of
      Cryptosporidium (now recognized as C. cuniculus) identical to those from human
      patients exhibiting symptoms of cryptosporidiosis. The high density of rabbits in
      many regions of Australia, including both rural and urban as well as natural
      water catchments areas, and the absence of any information on Cryptosporidium
      from lagomorphs in this country stimulated the present study. We undertook an
      epidemiological study that genetically characterized Cryptosporidium from rabbits
      from four locations in Victoria by PCR-coupled sequencing and phylogenetic
      analysis of sequence data for loci within the small subunit of nuclear ribosomal
      RNA (SSU; for specific identification) and the 60kDa glycoprotein gene (gp60; for
      genotypic/subgenotypic identification). Cryptosporidium was detected in 12 (6.8%)
      of 176 individual faecal samples. For SSU, all 12 sequences were identical to
      each other and to that of C. cuniculus. For pgp60, all corresponding sequences
      matched the known genotype Vb, and were classified as subgenotype VbA23R3 (n=11)
      and VbA26R4 (n=1), which are both new records. Present evidence indicates that
      genotype Vb is limited to rabbits; however, it would be premature to conclude
      that this genotype is not zoonotic. Future studies should focus on the zoonotic
      potential of C. cuniculus from rabbits and a wide range of yet unstudied animals.
      (Nucleotide sequences reported in this paper are available in the GenBank
      database under accession nos. HM852431-HM852433).

PMID- 20691810
TI  - Tnf-alpha expression and promoter sequences reflect the balance of
      tolerance/resistance to Puumala hantavirus infection in European bank vole
      populations.
AB  - The tumor necrosis factor-alpha (TNF-alpha) influences the ability to limit
      parasite infection but its over-production might result in inflammatory
      disorders. The level of Tnf-alpha gene expression could thus mediate a balance of
      tolerance/resistance to infections. This study focused on Puumala hantavirus
      (PUUV) infection in its rodent host, the bank vole (Myodes glareolus). In humans,
      PUUV is responsible of a mild form of hemorrhagic fever with renal syndrome,
      nephropathia epidemica (NE). The severity of NE is associated with an over
      production of TNF-alpha. By contrast, PUUV infection in bank vole is chronic and
      asymptomatic. It is likely that different coevolutionary histories between PUUV
      and its hosts could lead to different balances of resistance/tolerance to PUUV
      infection, at least partly mediated by variable production levels of TNF-alpha.
      We investigated the hypothesis that bank voles from PUUV endemic areas should
      exhibit higher levels of tolerance, i.e. lower levels of TNF-alpha production,
      than bank voles from areas where PUUV prevalence is low. For this purpose, we
      analysed variations of Tnf-alpha gene expression and promoter sequences among
      European populations of bank voles. Our results revealed an absence of up
      regulation of Tnf-alpha gene expression in PUUV infected bank voles and
      significant differences in Tnf-alpha gene expression level with regard to PUUV
      endemicity. These results corroborated the hypothesis of different balances of
      tolerance/resistance to PUUV. Two single-nucleotide polymorphism genotypes within
      the Tnf-alpha promoter (-302 GG/GG and -296 A/A) were associated with higher Tnf
      alpha gene expression and were more frequent in non-endemic areas. This study
      emphasized the potential influence of selection acting on TNF-alpha production
      and mediating a tolerance/resistance balance to PUUV in bank voles. Further
      investigations, including the role of phenotypic plasticity and parasite
      communities on Tnf-alpha expression levels, should provide important keys to
      understand the prevalence of PUUV over Europe.

PMID- 20691811
TI  - Further evidence of constrained radiation in the evolution of pathogenic
      Escherichia coli O157:H7.
AB  - Escherichia coli O157:H7 is a human pathogen that has emerged from its less
      pathogenic progenitor, E. coli O55:H7, to form the EHEC 1 clade. In its
      emergence, E. coli O157:H7 formed three distinct clusters, each of which exists
      today. Sequencing and SNP analysis of Cluster 1 of this clade demonstrated
      constrained radiation from the cluster founder. Here we investigated the
      diversity of Cluster 2 strains by sequencing signature SNPs in six strains
      collected throughout Washington State. Our results suggest that successful
      Cluster 2 strains have radiated on only two branches from their founder; one of
      these two branches leads to Cluster 3. Constrained radiation appears to be a
      common theme among this pathogenic clade.

PMID- 20691812
TI  - Dietary fatty acids and oxidative stress in the heart mitochondria.
AB  - Our study compared the effects of different oils on oxidative stress in rat heart
      mitochondria, as well as on plasma parameters used as risk factors for
      cardiovascular disease. The rats were fed for 16 weeks with coconut, olive, or
      fish oil diet (saturated, monounsaturated, or polyunsaturated fatty acids,
      respectively). The cardiac mitochondria from rats fed with coconut oil showed the
      lowest concentration of oxidized proteins and peroxidized lipids. The fish oil
      diet leads to the highest oxidative stress in cardiac mitochondria, an effect
      that could be partly prevented by the antioxidant probucol. Total and LDL
      cholesterols decreased in plasma of rats fed fish oil, compared to olive and
      coconut oils fed rats. A diet enriched in saturated fatty acids offers strong
      advantages for the protection against oxidative stress in heart mitochondria.

PMID- 20691813
TI  - The role of adenosine receptors in rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA), is the most common inflammatory musculoskeletal
      disease inducing diminished quality-of-life in the affected individuals and
      having major impact on society due to decrease work ability. Early diagnosis and
      immediate, effective therapy are crucial in order to prevent unfavorable outcome.
      Treatment of RA has progressed during the past two decades thanks to the advent
      of a large number of new agents targeting different specific molecules and
      pathways involved in the modulation of the inflammation. In this scenario an
      important role is covered by adenosine, a purine nucleoside released from a
      variety of cells in response to metabolic and inflammatory stress, which is
      considered to be a potent endogenous regulator acting through its interaction
      with 4 cell surface receptors named as A(1), A(2A), A(2B) and A(3). Adenosine
      receptor stimulation has complex effects on the release of pro-inflammatory
      cytokines depending on selective receptor engagement. Recent data show the
      involvement of adenosine pathways in RA and its potential therapeutic
      implications.

PMID- 20691814
TI  - Raman-assisted crystallography of biomolecules at the synchrotron:
      instrumentation, methods and applications.
AB  - Raman spectroscopy is a powerful technique that, in recent years, has been
      successfully coupled to X-ray crystallography for the analysis of biological
      macromolecular systems. The complementarity between both techniques is
      illustrated at multiple stages, including sample preparation, data collection and
      structural interpretation with a mechanistic perspective. The current state of
      instrumentation is described, focusing on synchrotron based setups. Present and
      future applications of Raman microspectrophotometry are reviewed with reference
      to recent examples dealing with metallo-, photosensitive-, and redox-proteins.
      The added value of Raman microspectrophotometry to assess X-radiation damage is
      discussed, and its applicability to investigate crystalline DNA molecules is also
      emphasized. This article is part of a Special Issue entitled: Protein Structure
      and Function in the Crystalline State.

PMID- 20691815
TI  - How different oxidation states of crystalline myoglobin are influenced by X-rays.
AB  - X-ray induced radiation damage of protein crystals is well known to occur even at
      cryogenic temperatures. Redox active sites like metal sites seem especially
      vulnerable for these radiation-induced reductions. It is essential to know
      correctly the oxidation state of metal sites in protein crystal structures to be
      able to interpret the structure-function relation. Through previous structural
      studies, we have tried to characterise and understand the reactions between
      myoglobin and peroxides. These reaction intermediates are relevant because
      myoglobin is proposed to take part as scavenger of reactive oxygen species during
      oxidative stress, and because these intermediates are similar among the haem
      peroxidases and oxygenases. We have in our previous studies shown that these
      different myoglobin states are influenced by the X-rays used. In this study, we
      have in detail investigated the impact that X-rays have on these different
      oxidation states of myoglobin. An underlying goal has been to find a way to be
      able to determine mostly unreduced states. We have by using single-crystal light
      absorption spectroscopy found that the different oxidation states of myoglobin
      are to a different extent influenced by the X-rays (e.g. ferric Fe(III) myoglobin
      is faster reduced than ferryl Fe(IV)?O myoglobin). We observe that the higher
      oxidation states are not reduced to normal ferrous Fe(II) or ferric Fe(III)
      states, but end up in some intermediate and possibly artificial states. For
      ferric myoglobin, it seems that annealing of the radiation-induced/reduced state
      can reversibly more or less give the starting point (ferric myoglobin). Both
      scavengers and different dose-rates might influence to which extent the different
      states are affected by the X-rays. Our study shows that it is essential to do a
      time/dose monitoring of the influence X-rays have on each specific redox-state
      with spectroscopic techniques like single-crystal light absorption spectroscopy.
      This will determine to which extent you can collect X-ray diffraction data on
      your crystal before it becomes too heavily influenced/reduced by X-rays. This
      article is part of a Special Issue entitled: Protein Structure and Function in
      the Crystalline State.

PMID- 20691816
TI  - Quantitative targeted biomarker assay for glycated haemoglobin by
      multidimensional LC using mass spectrometric detection.
AB  - The development of quantitative strategies for targeted biomarker analysis
      represents an urgent task especially in the field of clinical diagnosis. In this
      regard, the measurement of glycohaemoglobin (HbA(1c)) in blood has become the
      most specific way of monitoring long-term glycaemia in diabetic patients. Thus,
      there is an urgent need for methods that provide accurate and precise HbA(1c)
      results. A new method for the determination of HbA(1c) in blood samples based on
      the complementary use of multidimensional liquid chromatography (LC) and
      elemental (inductively coupled plasma mass spectrometry, ICP-MS) and molecular
      (electrospray-mass spectrometry, ESI-MS) MS techniques has been developed and
      validated. Different multidimensional separation possibilities by combining
      affinity and cation exchange chromatography have been explored for the adequate
      isolation of HbA(1c), which purity is addressed by ESI-MS. The workflow includes
      a final quantitative determination of HbA(1c) by elemental (Fe) isotope dilution
      analysis (IDA) with ICP-MS. For this purpose, the post-column addition of the
      isotopically labeled iron ((57)Fe) has been used to quantify the eluting Fe
      species from the column. The IDA methodology has been validated by analyzing a
      certified reference material and several samples from patients whose HbA(1c)
      levels were determined by a standard reference method.

PMID- 20691818
TI  - Low-molecular-weight heparin versus unfractionated heparin in acute ST-segment
      elevation myocardial infarction patients undergoing primary percutaneous coronary
      intervention with drug-eluting stents.

PMID- 20691820
TI  - Detection of elevated right atrial pressure using a simple bedside ultrasound
      measure.

PMID- 20691822
TI  - Effectiveness and safety of drug-eluting stents in vein grafts: a meta-analysis.

PMID- 20691823
TI  - A review of dyspnea in acute heart failure syndromes.
AB  - In acute heart failure syndrome (AHFS), dyspnea is one of the most common but
      least understood presenting symptoms for hospitalization. For this reason,
      dyspnea relief is increasingly becoming a focus in the development of therapies
      for the treatment of AHFS, and currently stands as an acceptable primary end
      point for regulatory approval by governmental agencies. This raises the question
      of how best to measure such a subjective symptom. In this review, we will
      describe the basis for dyspnea, provide a detailed description of the strengths
      and weaknesses of the current best tools used to measure it, and describe future
      directions for future development of dyspnea measurement in AHFS.

PMID- 20691824
TI  - Intramyocardial injection of autologous bone marrow mononuclear cells for
      patients with chronic ischemic heart disease and left ventricular dysfunction
      (First Mononuclear Cells injected in the US [FOCUS]): Rationale and design.
AB  - BACKGROUND: The increasing worldwide prevalence of coronary artery disease (CAD)
      continues to challenge the medical community. Management options include medical
      and revascularization therapy. Despite advances in these methods, CAD is a
      leading cause of recurrent ischemia and heart failure, posing significant
      morbidity and mortality risks along with increasing health costs in a large
      patient population worldwide. TRIAL DESIGN: The Cardiovascular Cell Therapy
      Research Network (CCTRN) was established by the National Institutes of Health to
      investigate the role of cell therapy in the treatment of chronic cardiovascular
      disease. FOCUS is a CCTRN-designed randomized, phase II, placebo-controlled
      clinical trial that will assess the effect of autologous bone marrow mononuclear
      cells delivered transendocardially to patients with left ventricular (LV)
      dysfunction and symptomatic heart failure or angina. All patients need to have
      limiting ischemia by reversible ischemia on single-photon emission computed
      tomography assessment. RESULTS: After thoughtful consideration of both
      statistical and clinical principles, we will recruit 87 patients (58 cell treated
      and 29 placebo) to receive either bone marrow-derived stem cells or placebo.
      Myocardial perfusion, LV contractile performance, and maximal oxygen consumption
      are the primary outcome measures. CONCLUSIONS: The designed clinical trial will
      provide a sound assessment of the effect of autologous bone marrow mononuclear
      cells in improving blood flow and contractile function of the heart. The target
      population is patients with CAD and LV dysfunction with limiting angina or
      symptomatic heat failure. Patient safety is a central concern of the CCTRN, and
      patients will be followed for at least 5 years.

PMID- 20691825
TI  - The new high-sensitivity cardiac troponin T assay improves risk assessment in
      acute coronary syndromes.
AB  - BACKGROUND: Cardiac troponins are currently the markers of choice for diagnosis
      of acute myocardial infarction and risk assessment in acute coronary syndrome
      (ACS). With the introduction of the new high-sensitivity cardiac troponin T (hs
      cTnT) assay, it has become possible to measure cTnT even in healthy subjects.
      However, how the hs-cTnT assay compares with the old cTnT assay for risk
      assessment in ACS is still unknown. METHODS: Cardiac troponin T levels were
      measured with the new hs-cTnT assay and the old third-generation cTnT assay in
      serum samples collected 48 hours after randomization in 1,452 randomly selected
      ACS patients enrolled in the GUSTO-IV trial. During 30 days of follow-up, deaths
      and myocardial infarctions were recorded. At 12 months, only all-cause mortality
      was collected. RESULTS: The 16% of the patients that had levels higher than the
      99th percentile cutoff for hs-cTnT but less than for cTnT had a similar 1-year
      mortality as the 60% that were positive for both assays (9.2% vs 10.7%, P = .52)
      and a higher 1-year mortality compared with the 24% that were negative for both
      assays (9.2% vs 2.6%, P = .001). For death or acute myocardial infarction at 30
      days, the group that was positive only for hs-cTnT had an intermediate risk
      compared with the groups negative or positive for both assays (2.4%, 5.2%, and
      8.7%; P < .001). CONCLUSION: The new hs-cTnT assay, compared with the old cTnT
      assay, identified more patients with myocardial damage and who were at an
      increased risk for new cardiac events.

PMID- 20691826
TI  - High burden of cardiovascular disease risk factors in Mexico: An epidemic of
      ischemic heart disease that may be on its way?
AB  - BACKGROUND: Whereas developed nations have witnessed a drop in the occurrence and
      mortality of ischemic heart disease, developing nations have recorded a constant
      rise. The burden of cardiovascular disease risk factors may explain this
      increase. METHODS: We conducted a population-based cross-sectional survey to
      estimate the prevalence of cardiovascular risk factors in the population
      protected by the Mexican Social Security Institute. A total of 20,062 Mexicans,
      aged >or=20 years, 43.5% (8,727) male and 56.5% (11,335) female, randomly
      selected in a 4-stage stratified population-based sampling process were included.
      RESULTS: The most prevalent cardiovascular risk factor in men was smoking
      (31.9%), whereas in women, it was obesity (26.6%) and central obesity (49.7%). A
      similar high age-adjusted prevalence was observed in women and men for
      hypertension (29.7% and 28.8%), diabetes (12.94% and 12.66%), and
      hypercholesterolemia (13.81% and 12.36%). There was a clear age effect on the
      prevalence of diabetes, hypertension, and hypercholesterolemia, with increasing
      prevalence with aging. Smoking also had an age effect, but its prevalence
      increases as age diminishes. More than half of the subjects in reproductive age
      (20-44 years old) have at least 1 cardiovascular risk factor, mainly smoking.
      CONCLUSIONS: Cardiovascular risk factors are highly prevalent in the Mexican
      population, which seems to be between the second and third stages of the tobacco
      epidemic. The increased prevalence of risk factors clustering indicates the need
      for comprehensive integrated management of cardiovascular risk factors in
      Mexicans, with special emphasis on individuals at younger ages.

PMID- 20691827
TI  - Transcatheter aortic valve implantation for severe aortic stenosis-a new paradigm
      for multidisciplinary intervention: a prospective cohort study.
AB  - BACKGROUND: Transcatheter aortic valve implantation (TAVI) is an alternative
      treatment option for patients with aortic stenosis deemed high risk or unsuitable
      for aortic valve replacement. The aim of this study was to assess the feasibility
      of TAVI in elderly patients, the delivery of this technology with a
      multidisciplinary approach, and the use of traditional surgical scoring systems.
      METHODS: One hundred fifty-one consecutive patients (mean age 82.6 +/- 7.3 years)
      with severe aortic stenosis underwent TAVI with the Edwards Lifesciences (Irvine,
      CA) Sapien bioprosthesis using the transapical (n = 84; 56%) or transfemoral (n =
      67; 44%) approach from August 2007 to September 2009 at King's Health Partners,
      London, United Kingdom. We analyzed procedural outcome, complications, functional
      status, and midterm outcome of patients. RESULTS: The multidisciplinary team
      comprised interventional cardiologists, cardiothoracic surgeons, imaging
      specialists, cardiac anesthetists, and specialist nurses. Seventy percent of
      patients were in New York Heart Association class III/IV, and logistic EuroSCORE
      was 21.6 +/- 11.9. Procedural success was achieved in 98%. Postoperative
      complications included stroke (6%), complete atrioventricular block (5.3%), renal
      failure requiring hemofiltration (9.3%), and vascular injury (8.6%). Overall 30
      day mortality was 9.9% (n = 15). The logistic EuroSCORE was a predictor of short
      term mortality (logistic regression model, P < .05). Thirty-day mortality post
      TAVI for patients with logistic EuroSCORE <20, 20 to 40, and >40 was 5.4%, 13.2%,
      and 22.2%, respectively. CONCLUSIONS: Transcatheter aortic valve implantation is
      a feasible treatment option in this patient group with promising short/medium
      term results. Renal failure is the commonest short-term complication, and the
      incidence of vascular complications remains high. Risk prediction/case selection
      remains challenging, and a multidisciplinary team approach appears to be helpful
      in appropriate patient selection.

PMID- 20691828
TI  - Application of appropriateness criteria to stress single photon emission computed
      tomography sestamibi studies: a comparison of the 2009 revised appropriateness
      criteria to the 2005 original criteria.
AB  - BACKGROUND: The 2005 appropriate use criteria (AUC) for stress single-photon
      emission computed tomographic myocardial perfusion imaging (SPECT MPI) were
      revised in 2009 to reflect changes in published evidence, clinical practice and
      experience with application of the 2005 AUC. The purpose of this study was to
      compare the 2009 AUC for SPECT MPI with the original 2005 criteria. METHODS:
      Using the Mayo Rochester Nuclear Cardiology Laboratory database, we
      retrospectively examined 281 patients who underwent stress SPECT MPI at Mayo
      Clinic Rochester between May 1, 2005, and May 15, 2005, using the revised 2009
      AUC and compared these findings to our previously published results in this same
      cohort using the 2005 AUC. RESULTS: Compared to the 2005 AUC, the 2009 AUC
      resulted in a highly significant overall change (P < .001) in the classification
      of appropriateness. The 2009 AUC eliminated unclassified patients, reduced
      appropriate studies (59.8% vs 63.7%, P = .02), increased studies of uncertain
      appropriateness (16.0% vs 10.7%, P = .01), and increased inappropriate studies
      (24.2% vs 14.6%, P < .001). CONCLUSIONS: In this cohort of patients undergoing
      SPECT MPI, compared to our previous study using the original 2005 AUC, the 2009
      AUC had a significant impact on the classification of appropriateness. The 2009
      AUC eliminated unclassified patients, increased inappropriate studies and
      increased studies of uncertain appropriateness.

PMID- 20691829
TI  - Joint effects of common genetic variants from multiple genes and pathways on the
      risk of premature coronary artery disease.
AB  - OBJECTIVE: The aim of this study is to discover common variants in 6 lipid
      metabolic genes and construct and validate a genetic risk score (GRS) based on
      the joint effects of genetic variants in multiple genes from lipid and other
      pathobiologic pathways. BACKGROUND: Explaining the genetic basis of coronary
      artery disease (CAD) is incomplete. Discovery and aggregation of genetic variants
      from multiple pathways may advance this objective. METHODS: Premature CAD cases
      (n = 1,947) and CAD-free controls (n = 1,036) were selected from our angiographic
      registry. In a discovery phase, single nucleotide polymorphisms (SNPs) at 56 loci
      from internal discovery and external reports were tested for associations with
      biomarkers and CAD: 28 promising SNPs were then tested jointly for CAD
      associations, and a GRS consisting of SNPs contributing independently was
      constructed and validated in a replication set of familial cases and population
      based controls (n = 1,320). RESULTS: Five variants contributed jointly to CAD
      prediction in a multigenic GRS model: odds ratio 1.24 (95% CI 1.16-1.33) per risk
      allele, P = 8.2 x 10(-11), adjusted OR 2.03 (1.53-2.70), fourth versus first
      quartile. 5-SNP genetic risk score had minor impact on area under the receiver
      operating characteristic curve (P > .05) but resulted in substantial net
      reclassification improvement: 0.16 overall, 0.28 in intermediate-risk patients
      (both P < .0001). GRS(5) predicted familial CAD with similar magnitude in the
      validation set. CONCLUSIONS: The Intermountain Healthcare's Coronary Genetics
      study demonstrates the ability of a multigenic, multipathway GRS to improve
      discrimination of angiographic CAD. Genetic risk scores promise to increase
      understanding of the genetic basis of CAD and improve identification of
      individuals at increased CAD risk.

PMID- 20691830
TI  - Economic analysis of a tailored behavioral intervention to improve blood pressure
      control for primary care patients.
AB  - BACKGROUND: Few telemedicine programs have undergone cost analyses, impeding
      their implementation into practice. We report on the economic analysis of a nurse
      administered intervention designed to improve blood pressure control among
      hypertensive veterans. METHODS: We randomized hypertensive patients at the Durham
      Veterans Affairs Medical Center primary care clinic to behavioral (n = 294) or
      nonbehavioral (n = 294) interventions. Behavioral intervention patients received
      tailored information bimonthly for 2 years via telephone. To calculate
      intervention cost, we microcosted the nurse's labor cost and computer hardware
      and software costs, applied a direct-to-indirect cost ratio, and distributed the
      costs over an estimated cohort of patients. We analyzed data from the Veterans
      Affairs Decision Support System to assess whether the intervention impacted
      overall health care utilization and costs. We used life expectancy estimates from
      the literature to develop decision models to calculate cost per life-year saved.
      RESULTS: The mean annual intervention cost was $112 (range $61-$259). During 2
      years of follow-up, patients in the intervention group incurred $7,800 in
      inpatient costs and $9,741 in outpatient costs; the nonintervention group
      incurred $6,866 in inpatient costs and $9,599 in outpatient costs. The total cost
      difference was not statistically significant (P = .56). Cost-effectiveness of the
      behavioral intervention ranged from $42,457 per life-year saved for normal-weight
      women to $87,300 per life-year saved for normal-weight men. CONCLUSIONS: The
      study results suggest that a nurse-administered, tailored behavioral intervention
      can be implemented at nominal cost and be cost-effective; however, there was no
      apparent lowering of health care utilization and costs during the 2 years of
      follow-up.

PMID- 20691831
TI  - Diuretic dose and long-term outcomes in elderly patients with heart failure after
      hospitalization.
AB  - BACKGROUND: The array of outcomes according to longitudinal furosemide doses in
      heart failure (HF) have not been evaluated. We examined the relationship of
      dynamic furosemide dose with mortality and hospitalizations for cardiovascular
      disease and renal dysfunction. METHODS: Among elderly patients with HF (>or=65
      years) newly discharged from hospital, dynamic furosemide exposure was determined
      by examining dose fluctuations up to 5 years of follow-up using the Ontario Drug
      Benefit pharmacare database. Dynamic furosemide exposures were classified as low
      dose (LD; 1-59 mg/d), medium dose (MD; 60-119 mg/d), or high dose (HD; >or=120
      mg/d). Outcomes were assessed by modeling furosemide exposure as a time-dependent
      covariate. RESULTS: Among 4,406 patients (78.4 +/- 7.0 years; 50.5% male), 46%
      changed furosemide dose categories within 1 year, and 63% changed dose categories
      over the follow-up period. High-dose furosemide patients were younger, were
      mostly male, and exhibited more ischemic or valvular disease, diabetes, atrial
      fibrillation, hypotension, hyponatremia, and higher baseline creatinine than LD.
      Compared with LD, MD exposure was associated with increased mortality with
      adjusted hazard ratio 1.96 (95% CI 1.79-2.15), whereas HD exposure conferred
      greater mortality risk with hazard ratio 3.00 (95% CI 2.72-3.31) after multiple
      covariate adjustment (both P < .001). Adjusted risks of hospitalization for HF
      (MD: 1.24 [95% CI 1.12-1.38] and HD: 1.43 [95% CI 1.26-1.63]), renal dysfunction
      (MD: 1.56 [95% CI 1.38-1.76] and HD: 2.16 [95% CI 1.88-2.49]), and arrhythmias
      (MD: 1.15 [95% CI 1.03-1.30] and HD: 1.45 [95% CI 1.27-1.66]) were also higher
      with increasing furosemide exposure. CONCLUSION: Exposure to higher furosemide
      doses is associated with worsened outcomes and is broadly predictive of death and
      morbidity.

PMID- 20691832
TI  - Predicting chronic left ventricular dysfunction 90 days after ST-segment
      elevation myocardial infarction: An Assessment of Pexelizumab in Acute Myocardial
      Infarction (APEX-AMI) Substudy.
AB  - OBJECTIVES: The purpose of this study was to determine predictors of 90-day left
      ventricular function following acute ST-segment elevation myocardial infarction
      (STEMI) using variables from clinical presentation, biomarker testing, and
      cardiovascular magnetic resonance imaging (CMR). BACKGROUND: Identifying patients
      with acute STEMI who experience adverse remodeling and develop left ventricular
      dysfunction 3 months post-MI is a priority for guiding subsequent therapy.
      METHODS: The Assessment of Pexelizumab in Acute Myocardial Infarction trial
      tested pexelizumab treatment in STEMI patients presenting within 6 hours of
      symptom onset who were to undergo primary percutaneous coronary intervention. We
      studied 64 patients within this trial according to a prespecified substudy that
      included paired core laboratory delayed-enhancement CMR at days 3 and 90 as well
      as plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP; in picograms per
      milliliter) measured at randomization and 24 hours. A multivariable model
      predicting day 90 left ventricular ejection fraction (LVEF) was developed from
      clinical, biomarker, and imaging findings. RESULTS: Patients had a median age of
      60 years (52-68), 89% were male, and 60% had anterior STEMI. Time from symptom
      onset to percutaneous coronary intervention was 3 hours. The median baseline LVEF
      was 48% (38%-56%) and was 50% (40%-54%) at 90 days: 7 patients (11%) had an LVEF
      <35% at 90 days. Patients with a lower 90-day LVEF (as a continuous variable) had
      a higher 24-hour NT-proBNP (P = .02) and a larger baseline infarct size by CMR
      (median 15% LV [8%-20% LV]) (P < .01). Microvascular obstruction (no reflow) was
      greater as measured by CMR (median 2.8% [1.4%-6.1%]) in patients with a lower 90
      day LVEF (P < .01). Median baseline and 24-hour NT-proBNP levels were 94 pg/mL
      (54-292 pg/mL) and 1,448 pg/mL (958-2,599 pg/mL), respectively. In a
      multivariable model with clinical, biomarker, and imaging variables, only 3
      variables independently predicted 90-day LVEF: 24-hour NT-proBNP, baseline CMR
      infarct size, and microvascular obstruction. CONCLUSIONS: Three key
      pathophysiologic variables of the post-STEMI myocardium measuring baseline
      infarct size and the extent of microvascular obstruction on CMR and wall tension
      (24-hour NT-proBNP) independently predicted 90-day LVEF. Further studies linking
      these measures with earlier use of clinical therapies may be warranted.

PMID- 20691833
TI  - Serum albumin concentration and heart failure risk The Health, Aging, and Body
      Composition Study.
AB  - BACKGROUND: How serum albumin levels are associated with risk for heart failure
      (HF) in the elderly is unclear. METHODS: We evaluated 2,907 participants without
      HF (age 73.6 +/- 2.9 years, 48.0% male, 58.7% white) from the community-based
      Health ABC Study. The association between baseline albumin and incident HF was
      assessed with standard and competing risks proportional hazards models
      controlling for HF predictors, inflammatory markers, and incident coronary
      events. RESULTS: During a median follow-up of 9.4 years, 342 (11.8%) participants
      developed HF. Albumin was a time-dependent predictor of HF, with significance
      retained for up to 6 years (baseline hazard ratio [HR] per -1 g/L 1.14, 95% CI
      1.06-1.22, P < .001; annual rate of HR decline 2.1%, 95% CI 0.8%-3.3%, P = .001).
      This association persisted in models controlling for HF predictors, inflammatory
      markers, and incident coronary events (baseline HR per -1 g/L 1.13, 95% CI 1.05
      1.22, P = .001; annual rate of HR decline 1.8%, 95% CI 0.5%-3.0%, P = .008) and
      when mortality was accounted for in adjusted competing risks models (baseline HR
      per -1 g/L 1.13, 95% CI 1.05-1.21, P = .001; annual rate of HR decline 1.9%, 95%
      CI 0.7%-3.1%, P = .002). The association of albumin with HF risk was similar in
      men (HR per -1 g/L 1.13, 95% CI 1.05-1.23, P = .002) and women (HR per -1 g/L
      1.12, 95% CI 1.04-1.22, P = .005) and in whites and blacks (HR per -1 g/L 1.13,
      95% CI 1.04-1.22, P< .01 for both races) in adjusted models. CONCLUSIONS: Low
      serum albumin levels are associated with increased risk for HF in the elderly in
      a time-dependent manner independent of inflammation and incident coronary events.

PMID- 20691834
TI  - Prognostic value of osteoprotegerin in chronic heart failure: The GISSI-HF trial.
AB  - BACKGROUND: Circulating levels of osteoprotegerin (OPG), a member of the tumor
      necrosis factor receptor superfamily, is predictive of death and hospitalization
      for heart failure after acute coronary syndrome. The association between OPG and
      outcome in patients with chronic heart failure (CHF) is unknown. METHODS: Plasma
      OPG levels at baseline were assessed in 1,229 patients with CHF recruited from 51
      clinical centers and included in the Gruppo Italiano per lo Studio della
      Sopravvivenza nell'Infarto Miocardico-Heart Failure (GISSI-HF) trial. Patients
      were randomized to n-3 polyunsaturated fatty acids (1 g/d) or rosuvastatin (10
      mg/d) versus placebo. Osteoprotegerin was analyzed by enzyme-linked immunosorbent
      assay. The association between OPG and outcome was assessed by Cox proportional
      hazards regression models. RESULTS: During a median follow-up time of 3.9 years,
      332 patients died; and 791 patients died or were hospitalized because of
      cardiovascular causes. By univariate analysis, baseline OPG levels were strongly
      associated with the incidence of death (hazard ratio {HR} [95% CI] 1.53 [1.40
      1.67] per 1-SD increase in log OPG). After adjustment for conventional risk
      markers, OPG remained a significant predictor of death (HR [95% CI] 1.20 [1.06
      1.35], P < .001). Similar findings were observed for the composite end point (HR
      [95% CI] 1.34 [1.07-1.69], P = .012). CONCLUSION: In patients with CHF, OPG is
      associated with the incidence of death independently of conventional
      cardiovascular risk factors.

PMID- 20691835
TI  - Correlation of heart-type fatty acid-binding protein with mortality and
      echocardiographic data in patients with pulmonary embolism at intermediate risk.
AB  - BACKGROUND: The management strategy in patients presenting with pulmonary
      embolism at intermediate risk still remains controversial. Our aim was to
      determine the role of heart-type fatty acid-binding protein (H-FABP) in this
      patient population. METHODS: One hundred one consecutive patients with confirmed
      pulmonary embolism and echocardiographic signs of right ventricular overload but
      without evidence for hypotension or shock, referred to as pulmonary embolism at
      intermediate risk, were included in the study. Heart-type fatty acid-binding
      protein and other biomarkers were measured in all patients upon arrival in the
      emergency department. RESULTS: Of the included 101 patients, 14 had positive H
      FABP tests. Ten patients with positive H-FABP (71%) had clinical deterioration
      during the hospital course and required inotropic support and 8 of these patients
      died. None of the 87 patients with a negative test worsened or needed inotropic
      support or died during hospital stay (P < .005). In the H-FABP-positive group,
      right ventricular function on echocardiography was more impaired (tricuspid
      annular plane systolic excursion 13 +/- 4 vs 18 +/- 4 mm, RV/LV ratio 1.1 +/- 0.2
      vs 0.9 +/- 0.2, presence of paradoxical septal movement 79% vs 46%, presence of
      McConnell sign 100% vs 60%, respectively, all P < .05) compared to the H-FABP
      negative group. After adjusting for potential confounding parameters, in
      multivariate analysis, H-FABP was the only independent predictor of mortality.
      CONCLUSIONS: Heart-type fatty acid-binding protein significantly predicts
      mortality in patients with pulmonary embolism at intermediate risk. Furthermore,
      it is significantly associated with impaired right ventricular function and shows
      better correlation with mortality than troponin I. It may be a novel prognostic
      parameter enabling the optimization of management strategy in the very difficult
      population of pulmonary embolism at intermediate risk.

PMID- 20691836
TI  - Prognostic value of exercise echocardiography in patients with left ventricular
      systolic dysfunction and known or suspected coronary artery disease.
AB  - BACKGROUND: The prognostic value of exercise echocardiography (ExE) in patients
      with left ventricular systolic dysfunction (LVSD) has not been characterized. We
      sought to assess the value of ExE for predicting outcome in patients with LVSD
      and known/suspected coronary artery disease. METHODS: This study is a
      retrospective analysis of a prospectively collected database of 1,107 patients
      who underwent treadmill ExE and had resting LVSD (left ventricular ejection
      fraction <50%). Ischemia was defined as an increase in wall motion score index
      from rest to exercise. The end points were all-cause mortality and major cardiac
      events (MACE). RESULTS: Overall, 494 patients (44.6%) developed new or worsening
      wall motion abnormalities. During a mean follow-up of 4.1 +/- 3.4 years, 301
      patients died and 166 had a MACE. In patients with mild LVSD, the 5-year
      mortality rate was 8.8% in those without ischemia and 21% in those with ischemia
      (P < .001). For patients with moderate LVSD without ischemia, the 5-year
      mortality rate was 18.3%, whereas it was 29.2% when ischemia was present (P =
      .009). In those with severe LVSD, the 5-year mortality rate was 23.9% without
      ischemia and 35.7% with ischemia (P = .03). In the multivariate analysis,
      increase in wall motion score index was an independent predictor of mortality
      (hazard ratio 2.25, 95% CI 1.26-2.06, P = .001) and MACE (hazard ratio 2.60, 98%
      CI 1.34-5.04, P = .005). The addition of the ExE results to clinical, resting
      echocardiography and exercise variables provided significant incremental
      prognostic information for predicting mortality (P = .001) and MACE (P = .005).
      CONCLUSIONS: The ExE provides significant information for predicting outcome in
      patients with LVSD and known/suspected coronary artery disease.

PMID- 20691837
TI  - Predictors of early readmission or death in elderly patients with heart failure.
AB  - BACKGROUND: Contemporary heart failure (HF) patients are elderly and have a high
      rate of early rehospitalization or death, resulting in a high burden for both the
      patients and the health care system. Prior studies were focused on younger and
      less well-characterized patients. We aimed to identify predictors of early
      hospital readmission and death in elderly patients with HF. METHODS: Patients
      with chronic HF taking part in the TIME-CHF study (n = 614, age 77 +/- 8 years,
      41% female, left ventricular ejection fraction 35% +/- 13%) were evaluated with
      respect to predictors of hospital readmission or death 30 and 90 days after
      inclusion. Demographic, clinical, laboratory, echocardiographic, and social
      variables were obtained at baseline and included in a multivariable logistic
      regression analysis to identify predictors of early events. RESULTS: The rate of
      hospital readmission or death was high at 30 (11%) and 90 days (26%). The reason
      for hospitalization was HF in 33%, other cardiovascular in 32%, and
      noncardiovascular in 45% of the cases, respectively. Predictors of readmission or
      death at 30 days were angina, lower systolic blood pressure, anemia, more
      extensive edema, higher creatinine levels, and dry cough; and at 90 days were
      coronary artery disease, prior pacemaker implantation, high jugular venous
      pressure, pulmonary rales, prior abdominal surgery, older age, and depressive
      symptoms. CONCLUSIONS: Early hospital readmission or death was frequent among
      elderly HF patients. A very large proportion of readmissions were due to
      noncardiovascular causes. In addition to clinical signs of HF, comorbidities are
      important predictors of early events in elderly HF patients.

PMID- 20691838
TI  - Aortic dissection in young adults who abuse amphetamines.
AB  - BACKGROUND: Case reports suggest a relationship between amphetamine
      abuse/dependence and aortic dissection, but no population-based epidemiologic
      studies have examined this link. Our objective was to test the hypothesis that
      young adults with a diagnosis of amphetamine abuse/dependence would be at higher
      risk for aortic dissection after accounting for known risk factors. METHODS: In
      this population-based case-control study of 30,922,098 discharges from the
      Healthcare Cost and Utilization Project Nationwide Inpatient Sample from 1995 to
      2007, among persons aged 18 to 49 years, we identified 3,116 thoracic and
      thoracoabdominal aortic dissections using International Classification of
      Disease, Ninth Edition, Clinical Modification codes 441.01 and 441.03. The
      SURVEYLOGISTIC procedure in SAS 9.2 (SAS Institute, Cary, NC) was used to account
      for the Nationwide Inpatient Sample sampling methodology. RESULTS: In a multiple
      logistic regression analysis, while controlling for known risk factors,
      amphetamine abuse/dependence was significantly associated with aortic dissection
      (adjusted odds ratio = 3.33, 95% CI = 2.37-4.69, P < .0001). CONCLUSIONS: This
      statistically significant association suggests that amphetamine abuse/dependence
      may play a role in aortic dissection in young adults in the United States.

PMID- 20691839
TI  - Cost and health outcome of primary percutaneous coronary intervention versus
      thrombolysis in acute ST-segment elevation myocardial infarction-Results of the
      Swedish Early Decision reperfusion Study (SWEDES) trial.
AB  - BACKGROUND: In ST-elevation myocardial infarction, primary percutaneous coronary
      intervention (PCI) has a superior clinical outcome, but it may increase costs in
      comparison to thrombolysis. The aim of the study was to compare costs, clinical
      outcome, and quality-adjusted survival between primary PCI and thrombolysis.
      METHODS: Patients with ST-elevation myocardial infarction were randomized to
      primary PCI with adjunctive enoxaparin and abciximab (n = 101), or to enoxaparin
      followed by reteplase (n = 104). Data on the use of health care resources, work
      loss, and health-related quality of life were collected during a 1-year period.
      Cost-effectiveness was determined by comparing costs and quality-adjusted
      survival. The joint distribution of incremental costs and quality-adjusted
      survival was analyzed using a nonparametric bootstrap approach. RESULTS: Clinical
      outcome did not differ significantly between the groups. Compared with the group
      treated with thrombolysis, the cost of interventions was higher in the PCI
      treated group ($4,602 vs $3,807; P = .047), as well as the cost of drugs ($1,309
      vs $1,202; P = .001), whereas the cost of hospitalization was lower ($7,344 vs
      $9,278; P = .025). The cost of investigations, outpatient care, and loss of
      production did not differ significantly between the 2 treatment arms. Total cost
      and quality-adjusted survival were $25,315 and 0.759 vs $27,819 and 0.728 (both
      not significant) for the primary PCI and thrombolysis groups, respectively. Based
      on the 1-year follow-up, bootstrap analysis revealed that in 80%, 88%, and 89% of
      the replications, the cost per health outcome gained for PCI will be <$0,
      $50,000, and $100,000 respectively. CONCLUSION: In a 1-year perspective, there
      was a tendency toward lower costs and better health outcome after primary PCI,
      resulting in costs for PCI in comparison to thrombolysis that will be below the
      conventional threshold for cost-effectiveness in 88% of bootstrap replications.

PMID- 20691840
TI  - Preoperative angiotensin-blocking drug therapy is not associated with atrial
      fibrillation after cardiac surgery.
AB  - BACKGROUND: Preoperative use of angiotensin-blocking drug therapy (ABDT) with
      angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers and
      its link to occurrence of postoperative atrial fibrillation (POAF), a common
      marker of poor outcomes after cardiac surgery, remain controversial. METHODS:
      From 1997 to 2003, 10,552 patients underwent coronary artery bypass grafting with
      or without valve surgery. To adjust for differences of clinical characteristics
      between patients who received ABDT within 24 hours before surgery compared with
      those who did not, propensity score analyses were conducted. RESULTS: Angiotensin
      blocking drug therapy was prescribed in 4,795 (45%) before surgery, of which
      1,725 (36%) developed POAF before discharge versus 1,908 (33%) of 5,757 patients
      who did not receive ABDT (unadjusted odds ratio 1.13, 95% CI 1.05-1.25, P < .01).
      In 6,744 propensity score-matched patients with well-balanced comorbidity
      profiles, ABDT was not associated with POAF (odds ratio 1.05, CI 0.95-1.16, P =
      .38). Stratified analysis within quintiles of propensity score and propensity
      adjusted logistic multivariable regression confirmed these findings. CONCLUSIONS:
      In this large observational study, we found no evidence of an association between
      preoperative angiotensin blockade and the occurrence of POAF. Adequately powered
      randomized studies are needed to clarify the best strategy of perioperative ABDT
      in patients with and without guideline-based indications.

PMID- 20691841
TI  - Comparison of the clinical outcome after pulmonary vein isolation based on the
      appearance of adenosine-induced dormant pulmonary vein conduction.
AB  - BACKGROUND: The elimination of transient pulmonary vein (PV) reconduction
      (dormant PV conduction) revealed by adenosine in addition to PV isolation reduced
      the atrial fibrillation (AF) recurrence after catheter ablation. The dormant PV
      conduction is induced in approximately half of the AF patients that undergo PV
      isolation. The present study compared the clinical outcome of AF ablation in
      patients whose dormant PV conduction was eliminated by additional radiofrequency
      applications with the outcome in patients without dormant conduction. METHODS: A
      total of 233 consecutive patients (206 male, 54.2 +/- 10.1 years) that underwent
      AF ablation were included in the present study. Dormant PV conduction was induced
      by the administration of adenosine triphosphate after PV isolation and was
      eliminated by supplemental radiofrequency application. All patients were followed
      up for >12 months (mean 903 days) after the first ablation. RESULTS: Following PV
      isolation, dormant PV conduction was induced in 139 (59.7%) of 233 patients and
      was successfully eliminated in 98% (223/228) of those in the first ablation
      procedure. After the first procedure, 63.9% (149/233) of patients were free from
      AF recurrence events. The success rates of a single or final AF ablation in
      patients with the appearance of the dormant PV conduction were similar to those
      of patients without dormant conduction (P = .69 and P = .69, respectively).
      CONCLUSIONS: Dormant PV conduction was induced in over half of the patients with
      AF. After the elimination of adenosine triphosphate-induced reconnection, the
      clinical outcome of patients with the dormant PV conduction was equivalent to
      that of patients without conduction.

PMID- 20691842
TI  - Adenosine diphosphate-induced platelet-fibrin clot strength: a new
      thrombelastographic indicator of long-term poststenting ischemic events.
AB  - BACKGROUND: Poststenting ischemic events occur despite dual-antiplatelet therapy,
      suggesting that a "one size fits all" antithrombotic strategy has significant
      limitations. Ex vivo platelet function measurements may facilitate risk
      stratification and personalized antiplatelet therapy. METHODS: We investigated
      the prognostic utility of the strength of adenosine diphosphate (ADP)-induced
      (MA(ADP)) and thrombin-induced (MA(THROMBIN)) platelet-fibrin clots measured by
      thrombelastography and ADP-induced light transmittance aggregation (LTA(ADP)) in
      225 serial patients after elective stenting treated with aspirin and clopidogrel.
      Ischemic and bleeding events were assessed over 3 years. RESULTS: Overall, 59
      (26%) first ischemic events occurred. Patients with ischemic events had higher
      MA(ADP), MA(THROMBIN), and LTA(ADP) (P < .0001 for all comparisons). By receiver
      operating characteristic curve analysis, MA(ADP) >47 mm had the best predictive
      value of long-term ischemic events compared with other measurements (P < .0001),
      with an area under the curve = 0.84 (95% CI 0.78-0.89, P < .0001). The univariate
      Cox proportional hazards model identified MA(ADP) >47 mm, MA(THROMBIN) >69 mm,
      and LTA(ADP) >34% as significant independent predictors of first ischemic events
      at the 3-year time point, with hazard ratios of 10.3 (P < .0001), 3.8 (P <
      .0001), and 4.8 (P < .0001), respectively. Fifteen bleeding events occurred.
      Receiver operating characteristic curve and quartile analysis suggests MA(ADP)
      <or=31 as a predictive value for bleeding. CONCLUSION: This study is the first
      demonstration of the prognostic utility of MA(ADP) in predicting long-term event
      occurrence after stenting. The quantitative assessment of ADP-stimulated platelet
      fibrin clot strength measured by thrombelastography can serve as a future tool in
      investigations of personalized antiplatelet treatment designed to reduce ischemic
      events and bleeding.

PMID- 20691843
TI  - Platelet response to clopidogrel and restenosis in patients treated predominantly
      with drug-eluting stents.
AB  - BACKGROUND: Preclinical studies suggest a relationship between early thrombotic
      response after vascular injury and later development of restenosis. The aim of
      this study was to assess the impact of platelet response to clopidogrel on the
      risk of restenosis after drug-eluting stenting (DES). METHODS: A total of 1,608
      consecutive patients were previously enrolled in a study on the relation between
      platelet reactivity and outcomes after DES. All patients received a loading dose
      of 600 mg clopidogrel. Blood samples for the assessment of adenosine diphosphate
      induced platelet aggregation with multiple electrode platelet aggregometry were
      drawn directly before percutaneous coronary intervention. Clopidogrel low
      response was defined as upper quintile of multiple electrode platelet
      aggregometry measurements. Accordingly, 323 patients (20%) were considered as low
      and 1,285 (80%) as normal responders. Primary end point of the present study was
      target lesion revascularization at 1 year. Secondary end points included binary
      angiographic restenosis and late lumen loss at 6- to 8-month angiography.
      RESULTS: Target lesion revascularization rates were comparable in both groups
      (10.9% vs 9.5%, hazard rate [HR] 1.2, 95% CI 0.8-1.7, P = .441). Follow-up
      angiography revealed no difference in binary angiographic restenosis (13.9% vs
      15.9%, P = .445) and late lumen loss (0.32 +/- 0.64 vs 0.35 +/- 0.63 mm, P =
      .477). Low responders had significantly more stent thromboses (2.5% vs 0.5%, HR
      5.4, 95% CI 1.9-15.6, P = .002), Q wave myocardial infarctions (2.5% vs 0.6%, HR
      4.0, 95% CI 1.5-10.7, P = .005), and ischemic strokes (1.3% vs 0.2%, HR 5.4, 95%
      CI 1.2-24.0, P = .028) at 1 year. CONCLUSION: Low platelet responsiveness to
      clopidogrel, a known predictor of thrombotic complications, does not have a
      significant impact on restenosis after DES.

PMID- 20691844
TI  - Incidence and clinical relevance of anti-platelet factor 4/heparin antibodies
      before cardiac surgery.
AB  - BACKGROUND: Heparin-induced thrombocytopenia (HIT) is caused by anti-platelet
      factor 4/heparin (PF4/H) immunoglobulin (Ig) G antibodies, which activate
      platelets. In some patients, anti-PF4/H antibodies are already detectable before
      cardiac surgery. Whether preoperative presence of antibodies confers adverse
      prognosis and which particular antibody classes (IgG, IgA, IgM) might be
      implicated are unknown. METHODS: We prospectively screened 591 patients
      undergoing cardiopulmonary bypass surgery for heparin-dependent antibodies by
      PF4/H immunoassay (separately for IgG, IgA, and IgM) and platelet activation test
      at preoperative baseline and at days 6 and 10. All patients received heparin or
      low-molecular-weight heparin postsurgery regardless of antibody status and were
      followed for postoperative complications, frequency of HIT, length of hospital
      stay, and 30-day mortality. RESULTS: Anti-PF4/H antibodies of any class were
      detected at preoperative baseline in 128 (21.7%) of 591 patients: IgG n = 44
      (7.4%), IgA n = 36 (6.1%), and IgM n = 79 (13.4%); some patients had >1 antibody
      class. Neither IgG nor IgA was a risk factor for any adverse outcome parameter.
      However, preoperative presence of IgM antibodies was associated with an increased
      risk for nonthromboembolic complications (all complications combined: hazard
      ratio 1.73, 95% CI 1.15-2.61) and a longer in-hospital stay (P = .02), but
      without evidence for increased risk of thrombotic complications or subsequent
      HIT. CONCLUSIONS: Patients with preoperative anti-PF4/H antibodies of IgG and IgA
      class are not at increased risk for thrombotic or nonthrombotic adverse events,
      whereas those with baseline anti-PF4/H IgM had an increased risk of nonthrombotic
      adverse outcomes but not of subsequent HIT or thrombosis. Because IgM antibodies
      do not cause HIT, they could represent a surrogate marker for other heparin
      independent risk factors.

PMID- 20691845
TI  - Organogenesis in development. Preface.

PMID- 20691846
TI  - How to make a heart: the origin and regulation of cardiac progenitor cells.
AB  - The formation of the heart is a complex morphogenetic process that depends on the
      spatiotemporally regulated contribution of cardiac progenitor cells. These mainly
      derive from the splanchnic mesoderm of the first and second heart field (SHF),
      with an additional contribution of neurectodermally derived neural crest cells
      that are critical for the maturation of the arterial pole of the heart. The
      origin and distinguishing characteristics of the two heart fields, as well as the
      relation of the SHF to the proepicardial organ and to a proposed third heart
      field are still subjects of debate. In the last ten years many genes that
      function in the SHF have been identified, leading to the establishment of a gene
      regulatory network in the mouse embryo. It is becoming increasingly evident that
      distinct gene networks control subdomains of the SHF that contribute to different
      parts of the heart. Although there is now extensive information about mutant
      phenotypes that reflect problems in the integration of progenitor cells into the
      developing heart, relatively little is known about the mechanisms that regulate
      SHF cell behavior. This important source of cardiac progenitor cells must be
      maintained as a proliferative, undifferentiated cell population. Selected
      subpopulations, at different development stages, are directed to myocardial, and
      also to smooth muscle and endothelial cell fates, as they integrate into the
      heart. Analysis of signaling pathways that impact the SHF, as well as regulatory
      factors, is beginning to reveal mechanisms that control cardiac progenitor cell
      behavior.

PMID- 20691847
TI  - Vascular development: genetic mechanisms and links to vascular disease.
AB  - Vertebrate development depends on the formation of intricate vascular networks at
      numerous sites and in precise patterns; these vascular networks supply oxygen and
      nutrients to the rapidly expanding tissues of the embryo. Embryonic blood vessels
      are composed of endothelial cells and pericytes that organize and expand into
      highly branched conduits. Proper development of the vasculature requires
      heterogeneity in the response of endothelial cells to angiogenic cues provided by
      other tissues and organs. The pathogenesis of vascular diseases results from
      genetic mutations in pathways that provide these cues and in signals that
      coordinate endothelial heterogeneity during blood vessel formation. Here we
      provide a brief overview of different aspects of blood vessel formation and then
      discuss three essential signaling pathways that help establish vessel networks
      and maintain endothelial phenotypic heterogeneity during vascular development:
      the vascular endothelial growth factor (VEGF), bone morphogenetic protein (BMP),
      and the Notch/Delta/Jagged pathways. The VEGF pathway is critical for the
      initiation and spatial coordination of angiogenic sprouting and endothelial
      proliferation, BMP signaling appears to act in a context-dependent manner to
      promote angiogenic expansion and remodeling, and the Notch pathway is a critical
      integrator of endothelial cell phenotypes and heterogeneity. We also discuss
      human genetic mutations that affect these pathways and the resulting pathological
      conditions.

PMID- 20691849
TI  - Transcriptional networks and signaling pathways that govern vertebrate intestinal
      development.
AB  - The vertebrate intestine is a complex and highly specialized organ comprising
      tissues derived from all three germ layers. While a description of the
      morphological events underlying the consolidation and organization of the
      endoderm, mesoderm, and ectoderm-derived cells into a multi-layered, continuously
      renewing organ has been available for several decades, only recently has a strong
      genetic framework for this process started to emerge, and as yet it remains
      incomplete. This review highlights the roles played by a number of transcription
      factors and signaling pathways in the development of the vertebrate intestine
      from the moment the definitive endoderm is formed. These molecular pathways often
      interact with each other and play multiple roles at different stages of
      intestinal formation. What is currently attracting considerable attention in the
      field is the realization that the deregulated activities of these same pathways
      often play a key role in the initiation and progression of a number of complex,
      serious intestinal diseases, including inflammatory bowel disease and cancer.

PMID- 20691850
TI  - Kidney development: two tales of tubulogenesis.
AB  - The mammalian kidney may well be one of the most complex organs of postnatal
      life. Each adult human kidney contains on average more than one million
      functional filtration units, the nephrons, residing within a specialized cellular
      interstitium. Each kidney also contains over 25 distinct cell types, each of
      which must be specifically aligned with respect to each other to ensure both
      normal development and ultimately, normal renal function. Despite this
      complexity, the development of the kidney can be simplistically described as the
      coordinate formation of two distinct sets of tubules. These tubules develop
      cooperatively with each other in time and space, yet represent two distinct but
      classical types of tubulogenesis. The first of these tubules, the ureteric bud,
      forms as an outgrowth of another epithelial tube, the nephric duct, and undergoes
      extensive branching morphogenesis to create the collecting system of the kidney.
      The second tubules are the nephrons themselves which arise via a mesenchyme-to
      epithelial transition induced by the first set of tubules. These tubules never
      branch, but must elongate to become intricately patterned and functionally
      segmented tubules. The molecular drivers for these two tales of tubulogenesis
      include many gene families regulating tubulogenesis and branching morphogenesis
      in other organs; however, the individual players and codependent
      interrelationships between a branched and non-branched tubular network make
      organogenesis in the kidney unique. Here we review both what is known and remains
      to be understood in kidney tubulogenesis.

PMID- 20691851
TI  - The game plan: cellular and molecular mechanisms of mammalian testis development.
AB  - In mammals, biological differences between males and females, which influence
      many aspects of their physical, social, and psychological environments, are
      solely determined genetically. In the presence of a Y chromosome, the gonadal
      primordium will differentiate into a testis, whereas in the absence of the Y
      chromosome an ovary will develop. Testis and ovary subsequently direct the
      differentiation of all secondary sex characteristics down the male and female
      pathway, respectively. The male-determining factor on the Y chromosome, SRY, was
      identified some 20 years ago. Since then, significant progress has been made
      toward understanding the molecular and cellular pathways that result in the
      formation of a testis. Here, we review what is known about testis differentiation
      in mice and humans, with reference to other species where appropriate.

PMID- 20691848
TI  - Lung organogenesis.
AB  - Developmental lung biology is a field that has the potential for significant
      human impact: lung disease at the extremes of age continues to cause major
      morbidity and mortality worldwide. Understanding how the lung develops holds the
      promise that investigators can use this knowledge to aid lung repair and
      regeneration. In the decade since the "molecular embryology" of the lung was
      first comprehensively reviewed, new challenges have emerged-and it is on these
      that we focus the current review. Firstly, there is a critical need to understand
      the progenitor cell biology of the lung in order to exploit the potential of stem
      cells for the treatment of lung disease. Secondly, the current familiar
      descriptions of lung morphogenesis governed by growth and transcription factors
      need to be elaborated upon with the reinclusion and reconsideration of other
      factors, such as mechanics, in lung growth. Thirdly, efforts to parse the finer
      detail of lung bud signaling may need to be combined with broader consideration
      of overarching mechanisms that may be therapeutically easier to target: in this
      arena, we advance the proposal that looking at the lung in general (and branching
      in particular) in terms of clocks may yield unexpected benefits.

PMID- 20691852
TI  - Building pathways for ovary organogenesis in the mouse embryo.
AB  - Despite its significant role in oocyte generation and hormone production in
      adulthood, the ovary, with regard to its formation, has received little attention
      compared to its male counterpart, the testis. With the exception of germ cells,
      which undergo a female-specific pattern of meiosis, morphological changes in the
      fetal ovary are subtle. Over the past 40 years, a number of hypotheses have been
      proposed for the organogenesis of the mammalian ovary. It was not until the turn
      of the millennium, thanks to the advancement of genetic and genomic approaches,
      that pathways for ovary organogenesis that consist of positive and negative
      regulators have started to emerge. Through the action of secreted factors (R
      spondin1, WNT4, and follistatin) and transcription regulators (beta-catenin and
      FOXL2), the developmental fate of the somatic cells is directed toward ovarian,
      while testicular components are suppressed. In this chapter, we review the
      history of studying ovary organogenesis in mammals and present the most recent
      discoveries using the mouse as the model organism.

PMID- 20691854
TI  - The molecular regulation of vertebrate limb patterning.
AB  - The limb has long been considered a paradigm for organogenesis because of its
      simplicity and ease of manipulation. However, it has become increasingly clear
      that the processes required to produce a perfectly formed limb involve complex
      molecular interactions across all three axes of limb development. Old models have
      evolved with acquisition of molecular knowledge, and in more recent times
      mathematical modeling approaches have been invoked to explain the precise spatio
      temporal regulation of gene networks that coordinate limb patterning and
      outgrowth. This review focuses on recent advances in our understanding of
      vertebrate limb development, highlighting the signaling interactions required to
      lay down the pattern on which the processes of differentiation will act to
      ultimately produce the final limb.

PMID- 20691855
TI  - Eye development.
AB  - The vertebrate eye comprises tissues from different embryonic origins: the lens
      and the cornea are derived from the surface ectoderm, but the retina and the
      epithelial layers of the iris and ciliary body are from the anterior neural
      plate. The timely action of transcription factors and inductive signals ensure
      the correct development of the different eye components. Establishing the genetic
      basis of eye defects in zebrafishes, mouse, and human has been an important tool
      for the detailed analysis of this complex process. A single eye field forms
      centrally within the anterior neural plate during gastrulation; it is
      characterized on the molecular level by the expression of "eye-field
      transcription factors." The single eye field is separated into two, forming the
      optic vesicle and later (under influence of the lens placode) the optic cup. The
      lens develops from the lens placode (surface ectoderm) under influence of the
      underlying optic vesicle. Pax6 acts in this phase as master control gene, and
      genes encoding cytoskeletal proteins, structural proteins, or membrane proteins
      become activated. The cornea forms from the surface ectoderm, and cells from the
      periocular mesenchyme migrate into the cornea giving rise for the future cornea
      stroma. Similarly, the iris and ciliary body form from the optic cup. The outer
      layer of the optic cup becomes the retinal pigmented epithelium, and the main
      part of the inner layer of the optic cup forms later the neural retina with six
      different types of cells including the photoreceptors. The retinal ganglion cells
      grow toward the optic stalk forming the optic nerve. This review describes the
      major molecular players and cellular processes during eye development as they are
      known from frogs, zebrafish, chick, and mice-showing also differences among
      species and missing links for future research. The relevance to human disorders
      is one of the major aspects covered throughout the review.

PMID- 20691853
TI  - Vertebrate skeletogenesis.
AB  - Vertebrate skeletogenesis consists in elaborating an edifice of more than 200
      pieces of bone and cartilage. Each skeletal piece is crafted at a distinct
      location in the body, is articulated with others, and reaches a specific size,
      shape, and tissue composition according to both species instructions and
      individual determinants. This complex, customized body frame fulfills multiple
      essential tasks. It confers morphological features, allows controlled postures
      and movements, protects vital organs, houses hematopoiesis, stores minerals, and
      adsorbs toxins. This review provides an overview of the multiple facets of this
      ingenious process for experts as well as nonexperts of skeletogenesis. We explain
      how the developing vertebrate uses both specific and ubiquitously expressed genes
      to generate multipotent mesenchymal cells, specify them to a skeletogenic fate,
      control their survival and proliferation, and direct their differentiation into
      cartilage, bone, and joint cells. We review milestone discoveries made toward
      uncovering the intricate networks of regulatory factors that are involved in
      these processes, with an emphasis on signaling pathways and transcription
      factors. We describe numerous skeletal malformation and degeneration diseases
      that occur in humans as a result of mutations in regulatory genes, and explain
      how these diseases both help and motivate us to further decipher skeletogenic
      processes. Upon discussing current knowledge and gaps in knowledge in the control
      of skeletogenesis, we highlight ultimate research goals and propose research
      priorities and approaches for future endeavors.

PMID- 20691856
TI  - Guide to techniques in mouse development. Preface.

PMID- 20691857
TI  - A survey of internet resources for mouse development.
AB  - The Internet contains many sources of information useful for mouse developmental
      biology research. These include anatomical atlases, gene expression atlases, and
      indexes to genetically engineered mouse strains and embryonic stem (ES) cells.
      Online atlases supersede earlier printed atlases in the quantity of available
      online images and the depth of specialized anatomical terminology and gene
      ontologies. Atlases annotated with gene expression data have increased value for
      comparisons with mouse models designed to study genetic perturbations of
      developmental processes. Gene expression libraries and microarray analyses of
      developmental stages are also available in Internet repositories. Bioinformatic
      interrogation of this data can identify regulatory gene networks and suggest
      putative transcriptional regulators that control cell fate. In silico formulated
      hypotheses about regulatory genes may be tested in vivo with mouse models
      obtained from the international Knockout Mouse Project (KOMP). Many of the genes
      targeted ES cells in KOMP are designed to mark cells with reporter molecules and
      produce conditional alleles. In combination with Cre recombinase mouse strains,
      genes can be inactivated at different developmental stages in specific cell types
      to study their function in embryogenesis. Atlases of mouse development, gene
      expression atlases, transcriptome databases, and repositories of genetically
      engineered mouse strains and ES cells are discussed.

PMID- 20691858
TI  - Transport of mouse lines by shipment of live embryos.
AB  - Advances in techniques for the genetic manipulation of the laboratory mouse have
      resulted in a vast array of novel mouse lines for research. One challenge facing
      researchers is the ability to rapidly share genetically modified mouse lines with
      collaborators at other institutions. The standard method of shipping live animals
      has its share of problems, including the acceptability of the mice at the
      receiving institution based on health status, as well as the length of time that
      mice are maintained in quarantine at the receiving institution. Transfer of mouse
      lines between institutions can also be accomplished by shipment of cryopreserved
      embryos or sperm. This option, however, is limited by the availability of
      properly trained staff at the shipping institution who can prepare the
      cryopreserved materials, as well as staff at the receiving institution who can
      recover live animals from the transferred samples. Overnight shipment of live,
      preimplantation mouse embryos circumvents many of the issues involved with
      shipping live animals or cryopreserved samples. The technique described in this
      chapter for shipping live embryos provides a simple method for transferring mouse
      lines between institutions.

PMID- 20691859
TI  - Strategies and considerations for distributing and recovering mouse lines.
AB  - As more and more genetically modified mouse lines are being generated, it becomes
      increasingly common to share animal models among different research institutions.
      Live mice are routinely transferred between animal facilities. Due to various
      issues concerning animal welfare, intellectual property rights, colony health
      status and biohazard, significant paperwork and coordination are required before
      any animal travel can take place. Shipping fresh or frozen preimplantation
      embryos, gametes, or reproductive organs can bypass some of the issues associated
      with live animal transfer, but it requires the receiving facilities to be able to
      perform delicate and sometimes intricate procedures such as embryo transfer, in
      vitro fertilization (IVF), or ovary transplantation. Here, we summarize the
      general requirements for live animal transport and review some of the assisted
      reproductive technologies (ART) that can be applied to shipping and reviving
      mouse lines. Intended users of these methods should consult their institution's
      responsible official to find out whether each specific method is legal or
      appropriate in their own animal facilities.

PMID- 20691860
TI  - Archiving and distributing mouse lines by sperm cryopreservation, IVF, and embryo
      transfer.
AB  - The number of genetically modified mouse lines has been increasing exponentially
      in the past few decades. In order to safeguard them from accidental loss and
      genetic drifting, to reduce animal housing cost, and to efficiently distribute
      them around the world, it is important to cryopreserve these valuable genetic
      resources. Preimplantation-stage embryos from thousands of mouse lines have been
      cryopreserved during the past two to three decades. Although reliable, this
      method requires several hundreds of embryos, which demands a sizable breeding
      colony, to safely preserve each line. This requirement imposes significant delay
      and financial burden for the archiving effort. Sperm cryopreservation is now
      emerging as the leading method for storing and distributing mouse lines, largely
      due to the recent finding that addition of a reducing agent, monothioglycerol,
      into the cryoprotectant can significantly increase the in vitro fertilization
      (IVF) rate in many mouse strains, including the most widely used C57BL/6 strain.
      This method is quick, inexpensive, and requires only two breeding age male mice,
      but it still remains tricky and strain-dependent. A small change in experimental
      conditions can lead to significant variations in the outcome. In this chapter, we
      describe in detail our sperm cryopreservation, IVF, and oviduct transfer
      procedures for storing and reviving genetically modified mouse lines.

PMID- 20691861
TI  - Isolation and manipulation of mouse gametes and embryos.
AB  - Many experimental approaches to answer questions about mammalian development
      begin with the isolation of mouse gametes and/or embryos. Here, methods used to
      isolate and store growing and fully-grown oocytes, ovulated (unfertilized) eggs,
      cleavage-stage embryos, and sperm from mice are described. Procedures used to
      carry out capacitation of sperm, binding of sperm to oocytes and ovulated eggs,
      and induction and assessment of the acrosome reaction in vitro are also
      described.

PMID- 20691862
TI  - Cryopreservation of mouse gametes and embryos.
AB  - As the use of genetically engineered mouse models continues to expand, the need
      to cryopreserve strains of mice increases in parallel in order to preserve these
      unique research resources and provide a low-cost alternative to maintaining the
      large inventory of strains. This chapter discusses methods for the
      cryopreservation of mouse embryos, sperm, and oocytes, and briefly discusses
      other requirements for implementing a successful cryopreservation program.

PMID- 20691863
TI  - Ovarian follicle culture systems for mammals.
AB  - Current approaches for the propagation and maintenance of mammalian ovarian
      follicles are reviewed in the context of the two dominant functional attributes
      of the follicle: sustaining oogenesis and regulating steroidogensis. Evidence is
      summarized indicating that the major utility for follicle cultures until recently
      has been to understand the steroidogenic properties of the follicle especially
      with regard to estrogen biosynthesis. Less stringent regulation of exposure to
      gonadotropins is tolerated in most systems when cell survival and differentiation
      are monitored for both the theca and granulosa components. In sharp contrast,
      establishing primary cultures of follicles for the maintenance of oogenesis is
      far more sensitive to a variety of experimental conditions and can in many cases
      compromise both the growth and maturative phases of oogenesis, a more recent
      focus for the applications of follicle culture in assisted reproductive
      technologies. Specific parameters that are discussed include media supplements,
      oocyte-granulosa interactions, culture atmosphere requirements, and maintenance
      of three-dimensional architecture. Limitations based upon species variations and
      the need for microfluidic devices are discussed in the context of clinically
      relevant translational goals especially as they pertain to the emerging field of
      fertility preservation.

PMID- 20691864
TI  - Production of mouse chimeras by aggregating pluripotent stem cells with embryos.
AB  - Experimental mouse chimeras have served as immensely important research tools for
      studying many aspects of mammalian development ever since they first were
      produced over 50 years ago. Chimera studies have served as crucial assays in the
      era of modern mouse genetics that was triggered by the advent of mouse embryonic
      stem cells. Lately, chimeras are also used as proof of pluripotency and normality
      of induced pluripotent stem cells. With this long history in mind, it may seem
      surprising that chimeras now have an ever-increasing role to play. The high
      throughput mouse gene targeting projects are in the process of producing ES cell
      lines with a mutation in each of the close to 20,000 known protein coding genes.
      These will all be waiting for germline transmission through chimeras. Such a
      large-scale approach calls for simplified methods for generating germline
      transmitting chimeras. In this chapter, we will describe the currently most cost
      efficient and simple method; the aggregation of pluripotent stem cells with
      diploid or tetraploid mouse embryos. Since most of the large knockout projects
      are using the C57BL/6 background, we will pay special attention to cell lines
      derived from this inbred strain.

PMID- 20691865
TI  - Production of cloned mice from somatic cells, ES cells, and frozen bodies.
AB  - Somatic cell nuclear transfer (SCNT) has become a unique and powerful tool for
      epigenetic reprogramming research and gene manipulation in animals. Although the
      success rates of somatic cloning have been inefficient and the mechanism of
      reprogramming is still largely unknown, therefore, the nuclear transfer (NT)
      method has been thought of as a "black box approach" and inadequate to determine
      the detail of how genomic reprogramming occurs. However, only the NT approach can
      reveal dynamic and global modifications in the epigenome without using genetic
      modification, as well as can create live animals. At present, this is the only
      technique available for the preservation and propagation of valuable genetic
      resources from mutant mice that are infertile or too old, or recovered from
      carcasses, without the use of germ cells. This chapter describes a basic protocol
      for mouse cloning and embryonic stem (ES) cell establishment from cloned embryo
      using a piezo-actuated micromanipulator. This technique will greatly help not
      only in mouse cloning but also in other forms of micromanipulation such as
      intracytoplasmic sperm injection (ICSI) into oocytes or ES cell injection into
      blastocysts. In addition, we describe a new, more efficient mouse cloning
      protocol using histone deacetylase inhibitor (HDACi), which increases the success
      rates of cloned mice or establish rate of ES cells to fivefold.

PMID- 20691866
TI  - Nuclear transfer in mouse oocytes and embryos.
AB  - Nuclear transfer methods provide an invaluable means of dissecting the genetic
      and epigenetic control of development, as well as the interactions between
      ooplasm and nucleus in the oocyte and early embryo. These procedures also provide
      novel means of manipulating animal genomes (e.g., through cloning with
      genetically engineered cells), and also have been applied for clinical purposes
      to treat infertility. This chapter reviews methods employed for a range of
      nuclear transfer techniques including germinal vesicle transfer, spindle
      transfer, intracytoplasmic sperm injection, pronuclear transfer, and somatic cell
      nuclear transfer.

PMID- 20691867
TI  - Culture of whole mouse embryos at early postimplantation to organogenesis stages:
      developmental staging and methods.
AB  - In vitro culture of whole mouse embryos enables the maintenance of growth and
      morphogenesis of postimplantation embryos outside the uterine environment. This
      technological advent facilitates the observation of the development of embryos in
      real time whereby cell lineage and tissue morphogenesis can be traced with
      appropriate vital cell labels and molecular markers. Embryos in culture are also
      amenable to direct experimental manipulations for elucidating developmental
      mechanisms of embryogenesis, germ layer formation, and embryonic patterning. This
      chapter outlines protocols for culturing mouse embryos at the immediate
      postimplantation period. We also present a system of developmental staging so
      that the outcome of different embryo culture studies may be assessed properly
      with reference to the precise developmental stage of the embryos used for the
      specific experiments.

PMID- 20691868
TI  - In utero and exo utero surgery on rodent embryos.
AB  - Mammalian development has been best characterized using the mouse model. Direct
      intervention of the postimplantation mouse embryo in utero represents one of many
      experimental approaches that can be used to probe mammalian embryogenesis.
      Experimental access to the mouse embryo is difficult, but techniques have been
      developed to circumvent some of the challenges of operating on the embryo in
      vivo. Experimental studies have been carried out on postimplantation stage
      embryos from E8.5 to term, so much of the gestational period is accessible for
      experimentation. One approach that has helped to enhance embryo accessibility was
      the development of surgical techniques based on the finding that embryonic
      development continued normally exo utero. Exo utero development refers to the
      surgically created condition in which the embryo develops outside of the uterine
      cavity, yet within the female abdominal cavity and attached, via the placenta, to
      the uterus. Using this approach it is feasible to carry out precise surgical
      manipulations of the mouse embryo without compromising embryo viability
      associated with postsurgery uterine contractions. In this chapter we review
      technical aspects of both in utero and exo utero surgical approaches and how
      these surgeries are used in conjunction with other experimental applications.

PMID- 20691869
TI  - Enhancement of IVF in the mouse by zona-drilling.
AB  - Cryopreservation of mouse sperm has become an essential method for the long-term
      storage of novel, genetically modified mouse lines. Cryopreserved sperm from most
      hybrid lines can be effectively used for in vitro fertilization (IVF) of mouse
      oocytes. Unfortunately, IVF recovery with cryopreserved sperm from inbred lines
      is very inefficient. This is especially troublesome since many transgenic lines
      are created on the popular C57Bl/6 inbred strain. Cryopreserved sperm from
      C57Bl/6 inbred and genetically modified lines is generally very inefficient when
      used in standard IVF recovery experiments, with fertilization rates that can be
      lower than 10%. Assisted reproductive techniques have been developed to improve
      the IVF efficiencies of cryopreserved inbred sperm. These techniques include zona
      drilling, which introduces a hole into the zona pellucida (ZP) surrounding mouse
      oocytes, using a chemical solution (acid Tyrode's), mechanical disruption
      (partial zona dissection or piezo-driven micropipette drilling), or laser
      photoablation. By allowing direct access of the sperm to the cytoplasmic
      membrane, zona-drilling can improve the efficiency of IVF fertilization rates
      with inbred sperm to greater than 90%, thus improving the chances of recovering
      mouse lines on inbred backgrounds that are maintained with cryopreserved sperm.
      The technique described in this chapter makes use of a piezo controller to
      mechanically disrupt the ZP, resulting in dramatic increases in the fertilization
      efficiency of cryopreserved sperm.

PMID- 20691870
TI  - ICSI in the mouse.
AB  - Fertilization by intracytoplasmic sperm injection (ICSI) is a powerful technique
      that can be used to understand better the biology of fertilization, in addition
      to a form of assisted reproduction both in humans and in endangered species.
      Mouse is often the model organism of choice to study mammalian fertilization. The
      ability to fertilize successfully mouse eggs by sperm injection, however, has
      been hard to achieve. The introduction of piezo-actuated injection made possible
      to perform mouse ICSI in an efficient fashion. Piezo-actuated ICSI is also
      currently used to fertilize eggs of other mammalian species, for injection of
      earlier spermatogenic cells into mouse eggs, as well as for somatic cell nuclear
      transfer, and cloning. This chapter provides detailed experimental procedures to
      perform ICSI in mouse eggs.

PMID- 20691871
TI  - A simple procedure for the efficient derivation of mouse ES cells.
AB  - Embryonic stem (ES) cells were first derived from inner cell mass (ICM) explants
      of preimplantation stage mouse blastocysts some 30 years ago. ES cells are of
      primary interest as they are used to genetically modify the genome of mice via
      gene targeting. Although many founder ES lines have been established, there is
      still a need to obtain new ES lines or their derivatives, often from new mutant
      mouse lines, to study the function of a mutated gene in different cell types.
      Existing methods for isolating ES cell lines are inefficient. Here, we describe a
      reproducible, efficient, and economical method to derive ES cells from different
      mouse strains using a defined serum-free, serum replacement (KO-SR) media, with
      50-85% efficiency. We have derived over 100 ES lines, which when karyotyped>70%
      were euploid. Two of these lines, when tested, produced germ-line chimeras. We
      also present procedures for the routine maintenance and karyotyping of the ES
      cells.

PMID- 20691872
TI  - Producing fully ES cell-derived mice from eight-cell stage embryo injections.
AB  - In conventional methods for the generation of genetically modified mice, gene
      targeted embryonic stem (ES) cells are injected into blastocyst-stage embryos or
      are aggregated with morula-stage embryos, which are then transferred to the
      uterus of a surrogate mother. F0 generation mice born from the embryos are
      chimeras composed of genetic contributions from both the modified ES cells and
      the recipient embryos. Obtaining a mouse strain that carries the gene-targeted
      mutation requires breeding the chimeras to transmit the ES cell genetic component
      through the germ line to the next (F1) generation (germ line transmission, GLT).
      To skip the chimera stage, we developed the VelociMouse method, in which
      injection of genetically modified ES cells into eight-cell embryos followed by
      maturation to the blastocyst stage and transfer to a surrogate mother produces F0
      generation mice that are fully derived from the injected ES cells and exhibit a
      100% GLT efficiency. The method is simple and flexible. Both male and female ES
      cells can be introduced into the eight-cell embryo by any method of injection or
      aggregation and using all ES cell and host embryo combinations from inbred,
      hybrid, and outbred genetic backgrounds. The VelociMouse method provides several
      unique opportunities for shortening project timelines and reducing mouse
      husbandry costs. First, as VelociMice exhibit 100% GLT, there is no need to test
      cross chimeras to establish GLT. Second, because the VelociMouse method permits
      efficient production of ES cell-derived mice from female ES cells, XO ES cell
      subclones, identified by screening for spontaneous loss of the Y chromosome, can
      be used to generate F0 females that can be bred with isogenic F0 males derived
      from the original targeted ES cell clone to obtain homozygous mutant mice in the
      F1 generation. Third, as VelociMice are genetically identical to the ES cells
      from which they were derived, the VelociMouse method opens up myriad
      possibilities for creating mice with complex genotypes in a defined genetic
      background directly from engineered ES cells without the need for inefficient and
      lengthy breeding schemes. Examples include creation of F0 knockout mice from ES
      cells carrying a homozygous null mutation, and creation of a mouse with a tissue
      specific gene inactivation by combining null and floxed conditional alleles for
      the target gene with a transgenic Cre recombinase allele controlled by a tissue
      specific promoter. VelociMice with the combinatorial alleles are ready for
      immediate phenotypic studies, which greatly accelerates gene function assignment
      and the creation of valuable models of human disease.

PMID- 20691873
TI  - The loss-of-allele assay for ES cell screening and mouse genotyping.
AB  - Targeting vectors used to create directed mutations in mouse embryonic stem (ES)
      cells consist, in their simplest form, of a gene for drug selection flanked by
      mouse genomic sequences, the so-called homology arms that promote site-directed
      homologous recombination between the vector and the target gene. The VelociGene
      method for the creation of targeted mutations in ES cells employs targeting
      vectors, called BACVecs, that are based on bacterial artificial chromosomes.
      Compared with conventional short targeting vectors, BacVecs provide two major
      advantages: (1) their much larger homology arms promote high targeting
      efficiencies without the need for isogenicity or negative selection strategies;
      and (2) they enable deletions and insertions of up to 100kb in a single targeting
      event, making possible gene-ablating definitive null alleles and other large
      scale genomic modifications. Because of their large arm sizes, however, BACVecs
      do not permit screening by conventional assays, such as long-range PCR or
      Southern blotting, that link the inserted targeting vector to the targeted locus.
      To exploit the advantages of BACVecs for gene targeting, we inverted the
      conventional screening logic in developing the loss-of-allele (LOA) assay, which
      quantifies the number of copies of the native locus to which the mutation was
      directed. In a correctly targeted ES cell clone, the LOA assay detects one of the
      two native alleles (for genes not on the X or Y chromosome), the other allele
      being disrupted by the targeted modification. We apply the same principle in
      reverse as a gain-of-allele assay to quantify the copy number of the inserted
      targeting vector. The LOA assay reveals a correctly targeted clone as having lost
      one copy of the native target gene and gained one copy of the drug resistance
      gene or other inserted marker. The combination of these quantitative assays makes
      LOA genotyping unequivocal and amenable to automated scoring. We use the
      quantitative polymerase chain reaction (qPCR) as our method of allele
      quantification, but any method that can reliably distinguish the difference
      between one and two copies of the target gene can be used to develop an LOA
      assay. We have designed qPCR LOA assays for deletions, insertions, point
      mutations, domain swaps, conditional, and humanized alleles and have used the
      insert assays to quantify the copy number of random insertion BAC transgenics.
      Because of its quantitative precision, specificity, and compatibility with high
      throughput robotic operations, the LOA assay eliminates bottlenecks in ES cell
      screening and mouse genotyping and facilitates maximal speed and throughput for
      knockout mouse production.

PMID- 20691874
TI  - Induced pluripotent stem cells.
AB  - Reprogramming of mouse and human somatic cells into induced pluripotent stem
      (iPS) cells has been possible with retroviral expression of the pluripotency
      associated transcription factors Oct4, Sox2, Nanog, and Lin28 as well as Klf4 and
      c-Myc. iPS cells hold great potential as a model for diseases from the
      perspective of the individual patient and as an alternative source of pluripotent
      stem cells for therapeutic applications. In this chapter, we discuss how the use
      of retroviruses as well as other expression vectors, protein transduction, and
      small molecules can effectively and efficiently induce pluripotent stem cells
      from a variety of mouse and human starting somatic cell populations.

PMID- 20691875
TI  - Imaging mouse embryonic development.
AB  - For the past three decades, methods for culturing mouse embryos ex vivo have been
      optimized in order to improve embryo viability and physiology throughout critical
      stages of embryogenesis. Combining advances made in the production of transgenic
      animals and in the development of different varieties of fluorescent proteins
      (FPs), time-lapse imaging is becoming more and more popular in the analysis of
      dynamic events during mouse development. Targeting FPs to specific cell types or
      subcellular compartments has enabled researchers to study cell proliferation,
      apoptosis, migration, and changes in cell morphology in living mouse embryos in
      real time. Here we provide a guide for time-lapse imaging of early stages of
      mouse embryo development.

PMID- 20691876
TI  - Imaging mouse development with confocal time-lapse microscopy.
AB  - The gene expression, signaling, and cellular dynamics driving mouse embryo
      development have emerged through embryology and genetic studies. However, since
      mouse development is a temporally regulated three-dimensional process, any
      insight needs to be placed in this context of real-time visualization. Live
      imaging using genetically encoded fluorescent protein reporters is pushing the
      envelope of our understanding by uncovering unprecedented insights into mouse
      development and leading to the formulation of quantitative accurate models.

PMID- 20691878
TI  - Use of transgenic fluorescent reporter mouse lines to monitor hematopoietic and
      erythroid development during embryogenesis.
AB  - The use of fluorescent reporter proteins such as GFP, RFP, and their variants to
      tag and track cells within the embryo has revolutionized developmental biology.
      Expression of these proteins within restricted populations has been achieved
      through the use of lineage-specific regulatory elements. This approach has proven
      especially powerful in the hematopoietic system, where it has been possible to
      monitor the generation, expansion, maturation, and migration of primitive
      erythroid cells, macrophages, and megakaryocytes during embryogenesis at
      unprecedented resolution. Such analyses have provided novel insights into the
      development of these lineages. In this chapter, we discuss the design
      considerations and methodologies involved in the production and analysis of
      transgenic mouse lines in which fluorescent reporters are expressed in the
      hematopoietic system of the mouse embryo.

PMID- 20691877
TI  - Ultrasound and magnetic resonance microimaging of mouse development.
AB  - Ultrasound biomicroscopy (UBM) and magnetic resonance microimaging (micro-MRI)
      provide noninvasive, high-resolution images in mouse embryos and neonates,
      enabling volumetric and functional analyses of phenotypes, including longitudinal
      imaging of individual mice over critical stages of in utero and early-postnatal
      development. In this chapter, we describe the underlying principles of UBM and
      micro-MRI, including the advantages and limitations of these approaches for
      studies of mouse development, and providing a number of examples to illustrate
      their use. To date, most imaging studies have focused on the developing nervous
      and cardiovascular systems, which are also reflected in the examples shown in
      this chapter, but we also discuss the future application of these methods to
      other organ systems.

PMID- 20691879
TI  - Identification and in vivo analysis of murine hematopoietic stem cells.
AB  - Hematopoietic stem cells (HSCs) can self-renew and give rise to all the cells of
      the blood and the immune system. As they differentiate, HSCs progressively lose
      their self-renewal capacity and generate lineage-restricted multipotential
      progenitor cells that in turn give rise to mature cells. The development of
      rigorous quantitative in vivo assays for HSC activity combined with multicolor
      flow cytometry and high-speed sorting have resulted in the phenotypic definition
      of HSCs to virtual purity. Here, we describe the isolation and identification of
      HSCs by flow cytometry and the use of competitive repopulation to assess HSC
      number and function.

PMID- 20691880
TI  - Penile cancer--update.

PMID- 20691881
TI  - Diagnosis and staging of penile cancer.
AB  - A comprehensive literature study was conducted to evaluate the levels of evidence
      (LEs) in publications on the diagnosis and staging of penile cancer.
      Recommendations from the available evidence were formulated and discussed by the
      full panel of the International Consultation on Penile Cancer in November 2008.
      The final grades of recommendation (GRs) were assigned according to the LEs of
      the relevant publications. The following consensus recommendations were accepted:
      physical examination of the primary penile lesion is mandatory, evaluating the
      morphologic and physical characteristics of the lesion (GR A). Evaluation of the
      primary lesion with ultrasonography is of limited value for local tumor staging
      (GR C); however, evaluation of the primary tumor with magnetic resonance (MRI)
      imaging during artificial erection induced by intracavernosal injection of
      prostaglandin might be more useful (GR B). Histologic or cytologic diagnosis of
      the primary lesion is mandatory (GR A). For accurate histologic grading and
      staging, a resected specimen is preferable to a biopsy specimen alone (GR B).
      Penile cancer should be staged according to the TNM system; however, the
      1987/2002 TNM staging system requires revision using data from larger patient
      cohorts to validate the recently proposed modifications (GR B). The
      histopathology report should provide information on all prognostic parameters,
      including the tumor size, histologic type, grade, growth pattern, depth of
      invasion, tumor thickness, resection margins, and lymphovascular and perineural
      invasion (GR B). Physical examination of the inguinal and pelvic areas to assess
      the lymph nodes is mandatory (GR B). Ultrasound-guided fine needle aspiration
      cytology is indicated for both palpable and nonpalpable inguinal nodes. If the
      findings confirm lymph node metastasis (LNM), complete inguinal lymph node
      dissection is indicated (GR B). In patients with nonpalpable inguinal nodes, if
      the ultrasound-guided fine needle aspiration cytology findings are negative for
      tumor, dynamic sentinel node biopsy can be performed if the equipment and
      technical expertise are available (GR C). In patients at high risk of inguinal
      LNM according to the available guidelines and nomograms, surgical staging can be
      performed by complete, bilateral inguinal lymph node dissection, which might also
      be curative (GR B). In patients at intermediate risk of LNM, sentinel node biopsy
      or modified (limited) inguinal lymph node dissection might be performed (GR B).
      In patients with nonpalpable inguinal nodes, imaging with computed tomography
      (CT) or MRI is not indicated, because they are not useful in detecting small
      volume LNM. Also, it is very unlikely that large-volume LNM (detectable by
      CT/MRI) would be present in the pelvic nodes (GR B). In patients with confirmed
      inguinal LNM, CT of the pelvis is indicated to detect iliac LNMs (GR B).
      Abdominal CT and chest radiography are advisable if the pelvic CT findings are
      positive (GR B).

PMID- 20691882
TI  - Epidemiology and natural history of penile cancer.
AB  - An extensive literature search was performed using the key words squamous cell
      carcinoma of the penis, phimosis, circumcision, chronic balanitis, cigarette
      smoking, genital warts and human papillomavirus (HPV) infection. All selected
      studies were classified according to the level of evidence (LE). The final grades
      of recommendation were assigned after discussion by the full panel of the
      International Consultation on Penile Cancer in November 2008. The factors
      positively associated with invasive penile cancers include the presence of
      phimosis (LE 3a), tobacco smoking (LE 3a-4), chewing tobacco (LE 3a), injury to
      the penis (LE 3a), balanitis (LE 3a), genital warts (LE 3a), and high-risk HPV
      infection (LE 3a-4).

PMID- 20691883
TI  - Penile cancer--prevention and premalignant conditions.
AB  - OBJECTIVES: Relatively little evidence is available in the published studies on
      the prevention of penile cancer and premalignant conditions of the penis. The
      present review examined the current evidence available in preventing penile
      cancer and pathologic subtypes of premalignant conditions and their treatment.
      The recommendations made in the present review formulate the basis of the recent
      2009 International Consultation on Urologic Disease Consensus Publishing Group.
      METHODS: The association of human papillomavirus subtypes and penile cancer is
      well-established, although the etiology, natural history, and treatment of
      premalignant lesions have mainly been reported in retrospective case series with
      short-term follow-up. The exact pathologic role of chronic inflammatory
      conditions, such as balanitis xerotica obliterans in the etiology of penile
      cancer remains largely unknown. RESULTS: Some of the potential strategies for the
      prevention of penile cancer could include circumcision, reducing the risk of
      transmission of penile human papillomavirus infection with male vaccination,
      early treatment of phimosis, smoking cessation, and hygienic measures.
      Implementing some of these measures would require extensive cost/benefit
      analysis, with significant changes in the global health policy. CONCLUSIONS:
      Owing to the current levels of evidence from published studies, firm guidelines
      cannot be formulated for the treatment of premalignant conditions, although
      preventative measures, such as reducing human papillomavirus transmission, could
      become strategic health targets.

PMID- 20691884
TI  - New developments in the treatment of localized penile cancer.
AB  - OBJECTIVES: To analyze the current trends in local therapy approaches in patients
      with penile carcinoma. METHODS: The relevant published data since 2000 were
      reviewed; important series published before 2000 were also included. The reports
      were classified according to the level of evidence. Review studies and others
      indirectly related to the topic were also included but not classified. RESULTS:
      New information has suggested that surgical margins of only a few millimeters
      might be adequate for most localized tumors. A trend toward the use of more
      conservative therapies instead of amputative surgery has been observed,
      especially in developed countries. Although the local recurrence rate has been
      greater after conservative therapies than after amputative surgery, this
      increased rate does not seemed to have had a negative effect on cancer-specific
      survival. The quality of life has been superior after conservative procedures
      with preservation of the penis that seems to give the best results with regard to
      sexual function. Reconstructive surgery can be performed in selected patients
      after amputative surgery. CONCLUSIONS: Although the level of evidence is low,
      conservative therapies can be recommended for selected patients with penile
      carcinoma. Despite the trend for conservative approaches, these patients need
      psychological support.

PMID- 20691885
TI  - Management of the lymph nodes in penile cancer.
AB  - A comprehensive literature study was conducted to evaluate the levels of evidence
      (LEs) in publications on the diagnosis and staging of penile cancer.
      Recommendations from the available evidence were formulated and discussed by the
      full panel of the International Consultation on Penile Cancer in November 2008.
      The final grades of recommendation (GRs) were assigned according to the LE of the
      relevant publications. The following consensus recommendations were accepted.
      Fine needle aspiration cytology should be performed in all patients (with
      ultrasound guidance in those with nonpalpable nodes). If the findings are
      positive, therapeutic, rather than diagnostic, inguinal lymph node dissection
      (ILND) can be performed (GR B). Antibiotic treatment for 3-6 weeks before ILND in
      patients with palpable inguinal nodes is not recommended (GR B). Abdominopelvic
      computed tomography (CT) and magnetic resonance imaging (MRI) are not useful in
      patients with nonpalpable nodes. However, they can be used in those with large,
      palpable inguinal nodes (GR B). The statistical probability of inguinal
      micrometastases can be estimated using risk group stratification or a risk
      calculation nomogram (GR B). Surveillance is recommended if the nomogram
      probability of positive nodes is <0.1 (10%). Surveillance is also recommended if
      the primary lesion is grade 1, pTis, pTa (verrucous carcinoma), or pT1, with no
      lymphovascular invasion, and clinically nonpalpable inguinal nodes, but only
      provided the patient is willing to comply with regular follow-up (GR B). In the
      presence of factors that impede reliable surveillance (obesity, previous inguinal
      surgery, or radiotherapy) prophylactic ILND might be a preferable option (GR C).
      In the intermediate-risk group (nomogram probability .1-.5 [10%-50%] or primary
      tumor grade 1-2, T1-T2, cN0, no lymphovascular invasion), surveillance is
      acceptable, provided the patient is informed of the risks and is willing and able
      to comply. If not, sentinel node biopsy (SNB) or limited (modified) ILND should
      be performed (GR B). In the high-risk group (nomogram probability >.5 [50%] or
      primary tumor grade 2-3 or T2-T4 or cN1-N2, or with lymphovascular invasion),
      bilateral ILND should be performed (GR B). ILND can be performed at the same time
      as penectomy, instead of 2-6 weeks later (GR C). SNB based on the anatomic
      position can be performed, provided the patient is willing to accept the
      potential false-negative rate of </=25% (GR C). Dynamic SNB with
      lymphoscintigraphic and blue dye localization can be performed if the technology
      and expertise are available (GR C). Limited ILND can be performed instead of
      complete ILND to reduce the complication rate, although the false-negative rate
      might be similar to that of anatomic SNB (GR C). Frozen section histologic
      examination can be used during SNB or limited ILND. If the results are positive,
      complete ILND can be performed immediately (GR C). In patients with cytologically
      or histologically proven inguinal metastases, complete ILND should be performed
      ipsilaterally (GR B). In patients with histologically confirmed inguinal
      metastases involving >/=2 nodes on one side, contralateral limited ILND with
      frozen section analysis can be performed, with complete ILND if the frozen
      section analysis findings are positive (GR B). If clinically suspicious inguinal
      metastases develop during surveillance, complete ILND should be performed on that
      side only (GR B), and SNB or limited ILND with frozen section analysis on the
      contralateral side can be considered (GR C). Endoscopic ILND requires additional
      study to determine the complication and long-term survival rates (GR C). Pelvic
      lymph node dissection is recommended if >/=2 proven inguinal metastases, grade 3
      tumor in the lymph nodes, extranodal extension (ENE), or large (2-4 cm) inguinal
      nodes are present, or if the femoral (Cloquet's) node is involved (GR C).
      Performing ILND before pelvic lymph node dissection is preferable, because pelvic
      lymph node dissection can be avoided in patients with minimal inguinal
      metastases, thus avoiding the greater risk of chronic lymphedema (GR B). In
      patients with numerous or large inguinal metastases, CT or MRI should be
      performed. If grossly enlarged iliac nodes are present, neoadjuvant chemotherapy
      should be given and the response assessed before proceeding with pelvic lymph
      node dissection (GR C). Antibiotic treatment should be started before surgery to
      minimize the risk of wound infection (GR C). Perioperative low-dose heparin to
      prevent thromboembolic complications can be used, although it might increase
      lymph leakage (GR C). The skin incision for ILND should be parallel to the
      inguinal ligament, and sufficient subcutaneous tissue should be preserved to
      minimize the risk of skin flap necrosis (GR B). Sartorius muscle transposition to
      cover the femoral vessels can be used in radical ILND (GR C). Closed suction
      drainage can be used after ILND to prevent fluid accumulation and wound breakdown
      (GR B). Early mobilization after ILND is recommended, unless a myocutaneous flap
      has been used (GR B). Elastic stockings or sequential compression devices are
      advisable to minimize the risk of lymphedema and thromboembolism (GR C).
      Radiotherapy to the inguinal areas is not recommended in patients without
      cytologically or histologically proven metastases nor in those with
      micrometastases, but it can be considered for bulky metastases as neoadjuvant
      therapy to surgery (GR B). Adjuvant radiotherapy after complete ILND can be
      considered in patients with multiple or large inguinal metastases or ENE (GR C).
      Adjuvant chemotherapy after complete ILND can be used instead of radiotherapy in
      patients with >/=2 inguinal metastases, large nodes, ENE, or pelvic metastases
      (GR C). Follow-up should be individualized according to the histopathologic
      features and the management chosen for the primary tumor and inguinal nodes (GR
      B).

PMID- 20691886
TI  - Treatment of visceral, unresectable, or bulky/unresectable regional metastases of
      penile cancer.
AB  - OBJECTIVES: To review the treatment strategies among patients with Stage IV
      penile cancer to describe potentially curative or palliative therapy. METHODS:
      The International Consultation on Urologic Disease for Penile Cancer subcommittee
      on the treatment of Stage IV penile cancer reviewed reports related to the topics
      of advanced penile cancer and metastatic penile cancer alone and combined with
      chemotherapy, radiotherapy, and inguinal lymphadenectomy. The reports were rated
      as to their level of evidence using the criteria of the Oxford Centre for
      evidence-based medicine. Treatment recommendations were made by consensus, with
      the appropriate grades determined from the level of evidence. RESULTS: The
      incidence of Stage IV disease using the current or modified TNM or Jackson
      descriptions was 0%-14%. Cisplatin-containing regimens were the most active, with
      patients exhibiting an average response and survival rate of 26% (range 15%-32%)
      and 5.5 months (range 4.7-7), respectively. Bleomycin-containing regimens were
      associated with significant pulmonary toxicity. The role of radiotherapy for
      advanced penile cancer has been largely palliative. Data have suggested that
      surgical consolidation among patients exhibiting an objective response to
      chemotherapy could be associated with durable survival. CONCLUSIONS: Treatment
      with a cisplatin-containing regimen in Stage IV penile cancer should be
      considered and might facilitate curative resection. The use of bleomycin was
      associated with a high level of toxicity and should be discouraged as first-line
      therapy. Surgical consolidation to achieve disease-free status or palliation
      should be considered in fit patients with an objective response to systemic
      chemotherapy. Palliative radiotherapy to inguinal or skeletal metastases might be
      of benefit.

PMID- 20691887
TI  - Prognostic factors in penile cancer.
AB  - OBJECTIVES: To review the published data concerning the prognostic factors in
      patients with penile squamous cell carcinoma (SCC). METHODS: We performed an
      extensive literature search using the MEDLINE databases. Multiple "free text"
      searches were performed, searching for the following terms individually in the
      fields title and abstract of the records: "squamous cell carcinoma," "penile
      cancer" and "prognostic factors." The search included all studies published in
      English until November 2008. All selected reports were classified according to
      the level of evidence (LE). The final grade of recommendation (GR) was determined
      by discussion among all panel members of the International Consultation on Penile
      Cancer in November 2008. RESULTS: The presence of metastases in the regional
      lymph nodes is the main factor predicting an unfavorable prognosis for patients
      with penile SCC (LE 3, GR B). The prognosis varies according to the number of
      positive lymph nodes, the presence of uni- or bilateral inguinal extension,
      pelvic node involvement, and the presence of lymph node capsular involvement (LE
      3, GR B). The histologic subtype, pathologic extension, histologic grade, and
      lymphatic and/or venous embolization are the most important variables of the
      primary tumor predicting for inguinal lymph node involvement (LE 3, GR B).
      CONCLUSIONS: The use of nomograms will allow for improvements in prognostic
      accuracy compared with the use of each single variable (LE 3, GR B). The use of
      molecular prognostic factors in clinical practice awaits additional confirmatory
      investigation (LE 3, GR B).

PMID- 20691888
TI  - Developments in the pathology of penile squamous cell carcinomas.
AB  - Most penile cancers are squamous cell carcinoma (SCC) originating in the
      epithelium covering glans, coronal sulcus, and foreskin. Several histologic
      subtypes have been described, each with distinctive clinicopathologic and outcome
      features. The most common subtype is the usual SCC, representing one half to two
      thirds of penile carcinomas. Penile verruciform tumors encompass verrucous, warty
      (condylomatous), and papillary, not otherwise specified, carcinomas. As a group,
      verruciform tumors are low grade, with low metastatic and mortality rates. In
      contrast, basaloid and sarcomatoid carcinomas are among the most aggressive
      penile tumors. Other SCC variants, such as carcinoma cuniculatum and
      pseudohyperplastic, adenosquamous and acantholytic carcinomas, are rare. The most
      relevant clinicopathologic and outcome features are outlined for each of these
      SCC subtypes, and an algorithm that might aid the pathologist in the histologic
      classification is presented. In addition, recommendations for handling penile
      cancer specimens, frozen section specimens, and pathology reports are provided.

PMID- 20691889
TI  - Stitching together cross-border research.

PMID- 20691890
TI  - Successes of genome-wide association studies.

PMID- 20691891
TI  - Strategies for genetic studies of complex diseases.

PMID- 20691893
TI  - Fyn-tau-amyloid: a toxic triad.
AB  - The axonal protein tau and amyloid beta-peptide (Abeta) are key players in the
      pathogenesis of Alzheimer's disease, and tau mediates Abeta toxicity, but it is
      not clear how. Ittner et al. (2010) now report an unexpected physiological
      function for tau in neuronal dendrites that may explain how tau mediates Abeta
      toxicity.

PMID- 20691894
TI  - Noncoding RNAs: the missing "linc" in p53-mediated repression.
AB  - The tumor suppressor protein p53 coordinates the cellular response to stress
      through regulation of gene expression. Now, Huarte et al. (2010) identify a long
      intergenic noncoding RNA as a new player in p53-mediated repression of genes
      involved in apoptosis.

PMID- 20691895
TI  - Stem cells and DNA damage: persist or perish?
AB  - Stem cells repopulate tissues after injury while also renewing themselves, but
      this makes them vulnerable to genotoxic damage. Mohrin et al. (2010) and
      Milyavsky et al. (2010) now show that mouse and human hematopoietic stem cells
      make opposing decisions about whether to die or to persist in response to DNA
      damage.

PMID- 20691896
TI  - Mitochondrial matrix reloaded with RNA.
AB  - Although mitochondrial biogenesis requires the import of specific RNAs, the
      pathways and cellular machineries involved are only poorly understood. Wang et
      al. (2010) now find that polynucleotide phosphorylase in the intermembrane space
      of mammalian mitochondria facilitates import of several RNAs into the
      mitochondrial matrix.

PMID- 20691897
TI  - A MAP for bundling microtubules.
AB  - Microtubules assemble into arrays of bundled filaments that are critical for
      multiple steps in cell division, including anaphase and cytokinesis. Recent
      structural and functional studies, including two papers in this issue of Cell
      (Bieling et al., 2010; Subramanian et al., 2010), demonstrate how the MAP65
      protein PRC1 crosslinks microtubules and cooperates with kinesin motors to
      control the dynamics and size of bundled regions.

PMID- 20691898
TI  - The pioneer round of translation: features and functions.
AB  - In mammalian cells, newly synthesized mRNAs undergo a pioneer round of
      translation that is important for mRNA quality control. Following maturation of
      messenger ribonucleoprotein particles during and after the pioneer round, steady
      state cycles of mRNA translation generate most of the cell's proteins.
      Translation factors, RNA-binding proteins, and targets of signaling pathways that
      are particular to newly synthesized mRNAs regulate critical functions of the
      pioneer round.

PMID- 20691899
TI  - Direct reprogramming of fibroblasts into functional cardiomyocytes by defined
      factors.
AB  - The reprogramming of fibroblasts to induced pluripotent stem cells (iPSCs) raises
      the possibility that a somatic cell could be reprogrammed to an alternative
      differentiated fate without first becoming a stem/progenitor cell. A large pool
      of fibroblasts exists in the postnatal heart, yet no single "master regulator" of
      direct cardiac reprogramming has been identified. Here, we report that a
      combination of three developmental transcription factors (i.e., Gata4, Mef2c, and
      Tbx5) rapidly and efficiently reprogrammed postnatal cardiac or dermal
      fibroblasts directly into differentiated cardiomyocyte-like cells. Induced
      cardiomyocytes expressed cardiac-specific markers, had a global gene expression
      profile similar to cardiomyocytes, and contracted spontaneously. Fibroblasts
      transplanted into mouse hearts one day after transduction of the three factors
      also differentiated into cardiomyocyte-like cells. We believe these findings
      demonstrate that functional cardiomyocytes can be directly reprogrammed from
      differentiated somatic cells by defined factors. Reprogramming of endogenous or
      explanted fibroblasts might provide a source of cardiomyocytes for regenerative
      approaches.

PMID- 20691900
TI  - Single-stranded DNA transposition is coupled to host replication.
AB  - DNA transposition has contributed significantly to evolution of eukaryotes and
      prokaryotes. Insertion sequences (ISs) are the simplest prokaryotic transposons
      and are divided into families on the basis of their organization and
      transposition mechanism. Here, we describe a link between transposition of IS608
      and ISDra2, both members of the IS200/IS605 family, which uses obligatory single
      stranded DNA intermediates, and the host replication fork. Replication direction
      through the IS plays a crucial role in excision: activity is maximal when the
      "top" IS strand is located on the lagging-strand template. Excision is stimulated
      upon transient inactivation of replicative helicase function or inhibition of
      Okazaki fragment synthesis. IS608 insertions also exhibit an orientation
      preference for the lagging-strand template and insertion can be specifically
      directed to stalled replication forks. An in silico genomic approach provides
      evidence that dissemination of other IS200/IS605 family members is also linked to
      host replication.

PMID- 20691901
TI  - A minimal midzone protein module controls formation and length of antiparallel
      microtubule overlaps.
AB  - During cell division, microtubules are arranged in a large bipolar structure, the
      mitotic spindle, to segregate the duplicated chromosomes. Antiparallel
      microtubule overlaps in the spindle center are essential for establishing
      bipolarity and maintaining spindle stability throughout mitosis. In anaphase,
      this antiparallel microtubule array is tightly bundled forming the midzone, which
      serves as a hub for the recruitment of proteins essential for late mitotic
      events. The molecular mechanism of midzone formation and the control of its size
      are not understood. Using an in vitro reconstitution approach, we show here that
      PRC1 autonomously bundles antiparallel microtubules and recruits Xklp1, a kinesin
      4, selectively to overlapping antiparallel microtubules. The processive motor
      Xklp1 controls overlap size by overlap length-dependent microtubule growth
      inhibition. Our results mechanistically explain how the two conserved, essential
      midzone proteins PRC1 and Xklp1 cooperate to constitute a minimal protein module
      capable of dynamically organizing the core structure of the central anaphase
      spindle.

PMID- 20691902
TI  - Insights into antiparallel microtubule crosslinking by PRC1, a conserved nonmotor
      microtubule binding protein.
AB  - Formation of microtubule architectures, required for cell shape maintenance in
      yeast, directional cell expansion in plants and cytokinesis in eukaryotes,
      depends on antiparallel microtubule crosslinking by the conserved MAP65 protein
      family. Here, we combine structural and single molecule fluorescence methods to
      examine how PRC1, the human MAP65, crosslinks antiparallel microtubules. We find
      that PRC1's microtubule binding is mediated by a structured domain with a
      spectrin-fold and an unstructured Lys/Arg-rich domain. These two domains, at each
      end of a homodimer, are connected by a linkage that is flexible on single
      microtubules, but forms well-defined crossbridges between antiparallel filaments.
      Further, we show that PRC1 crosslinks are compliant and do not substantially
      resist filament sliding by motor proteins in vitro. Together, our data show how
      MAP65s, by combining structural flexibility and rigidity, tune microtubule
      associations to establish crosslinks that selectively "mark" antiparallel overlap
      in dynamic cytoskeletal networks.

PMID- 20691903
TI  - Aurora kinases and protein phosphatase 1 mediate chromosome congression through
      regulation of CENP-E.
AB  - Opposing roles of Aurora kinases and protein phosphatase 1 (PP1) during mitosis
      have long been suggested. Here, we demonstrate that Aurora kinases A and B
      phosphorylate a conserved residue on the kinetochore motor CENP-E. PP1 binds CENP
      E via a motif overlapping this phosphorylation site and binding is disrupted by
      Aurora phosphorylation. Phosphorylation of CENP-E by the Auroras is enriched at
      spindle poles, disrupting binding of PP1 and reducing CENP-E's affinity for
      individual microtubules. This phosphorylation is required for CENP-E-mediated
      towing of initially polar chromosomes toward the cell center. Kinetochores on
      such chromosomes cannot make subsequent stable attachment to spindle microtubules
      when dephosphorylation of CENP-E or rebinding of PP1 to CENP-E is blocked. Thus,
      an Aurora/PP1 phosphorylation switch modulates CENP-E motor activity as an
      essential feature of chromosome congression from poles and localized PP1 delivery
      by CENP-E to the outer kinetochore is necessary for stable microtubule capture by
      those chromosomes.

PMID- 20691904
TI  - PNPASE regulates RNA import into mitochondria.
AB  - RNA import into mammalian mitochondria is considered essential for replication,
      transcription, and translation of the mitochondrial genome but the pathway(s) and
      factors that control this import are poorly understood. Previously, we localized
      polynucleotide phosphorylase (PNPASE), a 3' --> 5' exoribonuclease and poly-A
      polymerase, in the mitochondrial intermembrane space, a location lacking resident
      RNAs. Here, we show a new role for PNPASE in regulating the import of nuclear
      encoded RNAs into the mitochondrial matrix. PNPASE reduction impaired
      mitochondrial RNA processing and polycistronic transcripts accumulated. Augmented
      import of RNase P, 5S rRNA, and MRP RNAs depended on PNPASE expression and PNPASE
      imported RNA interactions were identified. PNPASE RNA processing and import
      activities were separable and a mitochondrial RNA targeting signal was isolated
      that enabled RNA import in a PNPASE-dependent manner. Combined, these data
      strongly support an unanticipated role for PNPASE in mediating the translocation
      of RNAs into mitochondria.

PMID- 20691907
TI  - SnapShot: Nonhomologous DNA end joining (NHEJ).

PMID- 20691905
TI  - Plzf regulates germline progenitor self-renewal by opposing mTORC1.
AB  - Hyperactivity of mTORC1, a key mediator of cell growth, leads to stem cell
      depletion, although the underlying mechanisms are poorly defined. Using
      spermatogonial progenitor cells (SPCs) as a model system, we show that mTORC1
      impairs stem cell maintenance by a negative feedback from mTORC1 to receptors
      required to transduce niche-derived signals. We find that SPCs lacking Plzf, a
      transcription factor essential for SPC maintenance, have enhanced mTORC1
      activity. Aberrant mTORC1 activation in Plzf(-/-) SPCs inhibits their response to
      GDNF, a growth factor critical for SPC self-renewal, via negative feedback at the
      level of the GDNF receptor. Plzf opposes mTORC1 activity by inducing expression
      of the mTORC1 inhibitor Redd1. Thus, we identify the mTORC1-Plzf functional
      interaction as a critical rheostat for maintenance of the spermatogonial pool and
      propose a model whereby negative feedback from mTORC1 to the GDNF receptor
      balances SPC growth with self-renewal.

PMID- 20691906
TI  - Myc-nick: a cytoplasmic cleavage product of Myc that promotes alpha-tubulin
      acetylation and cell differentiation.
AB  - The Myc oncoprotein family comprises transcription factors that control multiple
      cellular functions and are widely involved in oncogenesis. Here we report the
      identification of Myc-nick, a cytoplasmic form of Myc generated by calpain
      dependent proteolysis at lysine 298 of full-length Myc. Myc-nick retains
      conserved Myc box regions but lacks nuclear localization signals and the bHLHZ
      domain essential for heterodimerization with Max and DNA binding. Myc-nick
      induces alpha-tubulin acetylation and altered cell morphology by recruiting
      histone acetyltransferase GCN5 to microtubules. During muscle differentiation,
      while the levels of full-length Myc diminish, Myc-nick and acetylated alpha
      tubulin levels are increased. Ectopic expression of Myc-nick accelerates myoblast
      fusion, triggers the expression of myogenic markers, and permits Myc-deficient
      fibroblasts to transdifferentiate in response to MyoD. We propose that the
      cleavage of Myc by calpain abrogates the transcriptional inhibition of
      differentiation by full-length Myc and generates Myc-nick, a driver of
      cytoplasmic reorganization and differentiation.

PMID- 20691912
TI  - WFUMB Symposium on Safety of Nonmedical Use of Ultrasound.

PMID- 20691913
TI  - Nonmedical use of ultrasound: bioeffects and safety risk.

PMID- 20691914
TI  - Live scanning of pregnant models for equipment exhibitions.

PMID- 20691915
TI  - A new approach for improving coronary plaque component analysis based on
      intravascular ultrasound images.
AB  - Virtual histology intravascular ultrasound (VH-IVUS) is a clinically available
      technique for atherosclerosis plaque characterization. It, however, suffers from
      a poor longitudinal resolution due to electrocardiogram (ECG)-gated acquisition.
      This article presents an effective algorithm for IVUS image-based histology to
      overcome this limitation. After plaque area extraction within an input IVUS
      image, a textural analysis procedure consisting of feature extraction and
      classification steps is proposed. The pixels of the extracted plaque area
      excluding the shadow region were classified into one of the three plaque
      components of fibro-fatty (FF), calcification (CA) or necrotic core (NC) tissues.
      The average classification accuracy for pixel and region based validations is 75%
      and 87% respectively. Sensitivities (specificities) were 79% (85%) for CA, 81%
      (90%) for FF and 52% (82%) for NC. The kappa (kappa) = 0.61 and p value = 0.02
      indicate good agreement of the proposed method with VH images. Finally, the
      enhancement in the longitudinal resolution was evaluated by reconstructing the
      IVUS images between the two sequential IVUS-VH images.

PMID- 20691916
TI  - Focused maternal ultrasound by midwives in rural Zambia.
AB  - Point-of-care ultrasound is being increasingly implemented in resource-poor
      settings in an ad hoc fashion. We developed a focused maternal ultrasound
      training program for midwives in a rural health district in Zambia. Four hundred
      forty-one scans were recorded by 21 midwives during the 6-month study period. In
      74 scans (17%), the ultrasound findings prompted a change in clinical decision
      making. Eight of the midwives were evaluated with a 14-question observed
      structured clinical examination (OSCE) and demonstrated a slight overall
      improvement with mean scores at 2 and 6 months of 10.0/14 (71%) and 11.6/14
      (83%), respectively. Our pilot project demonstrates that midwives in rural Zambia
      can be trained to perform basic obstetric ultrasound and that it impacts clinical
      decision-making. Ultrasound skills were retained over the study period. More data
      is necessary to determine whether the introduction of ultrasound ultimately
      improves outcomes of pregnant women in rural Zambia.

PMID- 20691917
TI  - CAD algorithms for solid breast masses discrimination: evaluation of the accuracy
      and interobserver variability.
AB  - For a successful computer-aided diagnosis (CAD) approach, investigating the
      benefit of the output for radiologist diagnosis is as important as developing the
      computer algorithm itself. To evaluate the accuracy and the interobserver
      variability of two newly developed CAD algorithms for breast mass discrimination,
      eight radiologists with varied experience in breast ultrasonography (US)
      independently reviewed the lesions according to Breast Imaging Reporting and Data
      System (BI-RADS)-US. They interpreted the original ultrasound images, provided a
      final assessment category to indicate the probability of malignancy and then made
      a further diagnosis using the images processed by the proposed CAD algorithms.
      The receiver operating characteristic (ROC) curve and Cohen's kappa statistics
      were employed to evaluate the effect of the CAD algorithms on radiologist
      diagnoses. By using the proposed CAD approach, the quality of the images was
      improved and more information was provided to the observers. With the processed
      images, the areas under the ROC (Az) of each reader (0.86 approximately 0.89)
      were greater than those with the original ultrasound images (0.81 approximately
      0.86) and all the radiologists improved their performance significantly (p <
      0.05) except two senior radiologists (p > 0.05). The Az values of the junior
      radiologists with CAD were comparable to those of the senior radiologists.
      Cohen's kappa statistics showed that better interobserver agreement was obtained
      by using the processed images. We conclude that the proposed CAD method is more
      helpful for the junior radiologists than for the senior ones and it also showed
      the advantage of decreasing interobserver variability.

PMID- 20691918
TI  - Evaluating biliary anatomy and variations in living liver donors by a new
      technique: three-dimensional contrast-enhanced ultrasonic cholangiography.
AB  - Accurate assessment of the biliary anatomy is important for the safety of liver
      donors in living donor liver transplantation (LDLT). We evaluated the biliary
      anatomy and variations of 12 living liver donors with 3-D contrast-enhanced
      ultrasonic cholangiography (3-D CEUSC) by injecting microbubble contrast agents
      into the common hepatic ducts intraoperatively. Two radiologists assessed the
      diagnostically adequate, delineation of biliary branch orders, visibility scores
      (grades 0 to 3) and anatomical patterns of the intrahepatic biliary tree by
      consensus. The results were compared with findings on intraoperative
      cholangiography (IOC) and surgery. 3-D CEUSC successfully demonstrated the
      spatial structure of the intrahepatic biliary tree in all 12 donors. The maximum
      branching order of intrahepatic bile ducts displayed on 3-D CEUSC was the fifth
      order in the right lobe and fourth order in the left lobe of the liver,
      respectively. The visibility scores of the first-order (3.00 +/- 0.00) and second
      order (2.67 +/- 0.69) branches were significantly (p < 0.001) higher than that of
      the third-order (1.98 +/- 1.13) branches, whereas visibility scores of the second
      order (2.88 +/- 0.34) and third-order (2.44 +/- 1.01) branches in the right lobe
      were significantly (p = 0.040 and p < 0.001, respectively) higher than those in
      the left lobe (2.46 +/- 0.88 and 1.33 +/- 0.99). The 3-D CEUSC images of the 12
      donors were diagnostically adequate for evaluating the biliary anatomy. Normal
      biliary pattern in nine donors and biliary variations in three donors were
      confirmed by both IOC and surgical findings. 3-D CEUSC may be a potential
      alternative to IOC in the evaluation of biliary anatomical variation before graft
      harvesting in LDLT.

PMID- 20691919
TI  - The effect of variable waveform low-intensity pulsed ultrasound in a fourth
      metacarpal osteotomy gap model in horses.
AB  - The objective of this study was to evaluate the effects of variable waveform low
      intensity ultrasound on the healing of a fracture gap of the fourth metacarpal
      bone in horses. A randomized, blinded, controlled trial was conducted in eight
      healthy adult horses. In each horse, a 1-cm osteotomy of the fourth metacarpal
      bone was created. One randomly selected metacarpal gap was treated daily with a
      40-min session of ultrasound and the opposite gap was managed similarly with an
      inactive transducer. The fourth metacarpal bones were radiographed weekly.
      Fluorescent markers were administered at 14, 28, 56 and 70 d. At the completion
      of the study at day 84, the bones were harvested and evaluated with peripheral
      quantitative computed tomography (pQCT) and histology. There were no significant
      differences between treated and control bones for any of the radiographic, pQCT
      or histologic parameters evaluated. These findings suggested that low-intensity
      ultrasound did not affect bone formation in a fracture gap model in the horse.

PMID- 20691920
TI  - Extracorporeal shockwaves versus surgery in the treatment of pseudoarthrosis of
      the carpal scaphoid.
AB  - The peculiar anatomical characteristics and precarious vascularization of the
      carpal scaphoid are responsible for a difficult healing of fractures and a fairly
      frequent subsequent evolution to pseudoarthrosis. Recently, extracorporeal
      shockwaves therapy (ESWT) has yielded encouraging results in the treatment of
      pseudoarthrosis of various bone segments. We report a retrospective study
      comparing the results of application of three sessions of shockwaves therapy (SW)
      with energy flux density (EFD) impulses of 0.09 (SD = 0.02) mJ/mm(2) ESWT emitted
      by an electromagnetic generator in 58 patients (group I) affected by
      pseudoarthrosis of the carpal scaphoid, with the results of surgical treatment
      consisting of stabilization and bone graft according to the Matti-Russe
      technique, performed in 60 subjects (controls, group II). There were no
      statistically significant differences in the mean duration of the pseudoarthrosis
      (p = 0.46), sex distribution (p = 0.41) and mean age at recruitment (p = 0.95)
      between the two patient groups. Posttreatment clinical-functional assessment,
      based on the Mayo Wrist Score, showed a significantly improved score, rising from
      28-74.6 in group I already after 2 mo (p < 0.001), with 86.3% of the results
      judged as satisfactory or excellent; in group II the mean score rose from 27.5
      74.2 after 2 mo, with 83.4% of the results judged as satisfactory or excellent (p
      < 0.001). At the same two-months follow-up (FU), radiographic consolidation was
      shown in 75.9% of patients in group I and 76.7% in group II. These improvements
      persisted at the subsequent controls at six and 12 mo in both groups. The Mayo
      Wrist Score and X-rays did not show statistically significant differences at the
      various FU visits in the two groups (p > 0.05). On the basis of our data, we can
      conclude that the results of ESWT are comparable with those of surgical
      stabilization and bone graft in the treatment of scaphoid pseudoarthrosis. In
      view of their minimal invasiveness, shockwaves should therefore be considered the
      treatment of choice of this disorder.

PMID- 20691921
TI  - Computational evaluation of the compositional factors in fracture healing
      affecting ultrasound axial transmission measurements.
AB  - This work aimed at computationally evaluating the compositional factors in
      fracture healing affecting ultrasound axial transmission (UAT), using four
      numerical daily-changing healing models, representing more realistic clinical
      conditions. Using two-dimensional (2-D) simulations, a 1-MHz source and a
      receiver were positioned parallel to the bone surface to detect the first
      arriving signal (FAS). The time-of-flight of the FAS (TOF(FAS)) was found to be
      sensitive only to superficial modifications in the propagation path. It was also
      shown that callus mature bone better explained alone the variation in TOF(FAS)
      (R(2) >or= 0.70, p < 0.001). Better TOF(FAS) predictions are obtained when using
      the callus composition inside cortical fracture gap (R(2) = 0.98, p < 0.01).
      Callus composition could not well explain the changes in energy attenuation.
      These results suggest that UAT may be an important clinical tool for fracture
      healing assessment, identifying callus degree of mineralization and possible
      consolidation delays and nonunions.

PMID- 20691922
TI  - A study of bubble activity generated in ex vivo tissue by high intensity focused
      ultrasound.
AB  - Cancer treatment by extracorporeal high-intensity focused ultrasound (HIFU) is
      constrained by the time required to ablate clinically relevant tumour volumes.
      Although cavitation may be used to optimize HIFU treatments, its role during
      lesion formation is ambiguous. Clear differentiation is required between acoustic
      cavitation (noninertial and inertial) effects and bubble formation arising from
      two thermally-driven effects (the vapourization of liquid into vapour, and the
      exsolution of formerly dissolved permanent gas out of the liquid and into gas
      spaces). This study uses clinically relevant HIFU exposures in degassed water and
      ex vivo bovine liver to test a suite of cavitation detection techniques that
      exploit passive and active acoustics, audible emissions and the electrical drive
      power fluctuations. Exposure regimes for different cavitation activities (none,
      acoustic cavitation and, for ex vivo tissue only, acoustic cavitation plus
      thermally-driven gas space formation) were identified both in degassed water and
      in ex vivo liver using the detectable characteristic acoustic emissions. The
      detection system proved effective in both degassed water and tissue, but requires
      optimization for future clinical application.

PMID- 20691923
TI  - Site dependence of thickness and speed of sound in articular cartilage of bovine
      patella.
AB  - Researchers have made efforts to quantify thickness of articular cartilage as
      well as its acoustic and mechanical properties using various ultrasound (US)
      techniques during the last decades, because they are important indicators of
      articular cartilage degeneration. However, the variation of the thickness and
      speed of sound of articular cartilage at different anatomical sites would result
      in the uncertainty of US assessment of degeneration. In this paper, the site
      dependences of speed of sound and thickness of bovine patellar articular
      cartilage (n = 10) were investigated using a custom-made US measurement system.
      The thickness and speed of sound of articular cartilage at different locations of
      the bovine patella were measured on excised specimens ex situ using a noncontact
      US approach. A total of 10 patellae were tested. The results showed the overall
      mean value of the speed of sound in the articular cartilage at the 25 measured
      sites was 1626 +/- 86 m/s (range, 1507 to 1834 m/s). No statistically significant
      difference in the speed of sound was observed among the 25 locations or among the
      four quadrants of the patella. The highest speed of sound (1834 +/- 74 m/s) was
      obtained at the medial-upper quadrant and the lowest value (1507 +/- 74 m/s) at
      the medial-lower quadrant. Further grouping of the data revealed that the speed
      of sound in the central region (1633 +/- 21 m/s) was significantly (p < 0.01)
      larger than that for the surrounding region (1621 +/- 22 m/s). The overall mean
      thickness of the patellar articular cartilage was 1.34 +/- 0.34 mm. No
      significant difference was obtained in the thickness among the 25 locations and
      also among the four quadrants. However, when the thickness values were divided
      diagonally, a significant difference (p < 0.01) was observed between the upper
      region (1.27 +/- 0.11 mm) and the lower region (1.31 +/- 0.41 mm) of the
      patellae. Although no significant differences in the thickness and speed of sound
      among the tested sites were observed, it was demonstrated in this study that they
      did show some degree of site dependence.

PMID- 20691924
TI  - SRBF: Speckle reducing bilateral filtering.
AB  - Speckle noise negatively affects medical ultrasound image shape interpretation
      and boundary detection. Speckle removal filters are widely used to selectively
      remove speckle noise without destroying important image features to enhance
      object boundaries. In this article, a fully automatic bilateral filter tailored
      to ultrasound images is proposed. The edge preservation property is obtained by
      embedding noise statistics in the filter framework. Consequently, the filter is
      able to tackle the multiplicative behavior modulating the smoothing strength with
      respect to local statistics. The in silico experiments clearly showed that the
      speckle reducing bilateral filter (SRBF) has superior performances to most of the
      state of the art filtering methods. The filter is tested on 50 in vivo US images
      and its influence on a segmentation task is quantified. The results using SRBF
      filtered data sets show a superior performance to using oriented anisotropic
      diffusion filtered images. This improvement is due to the adaptive support of
      SRBF and the embedded noise statistics, yielding a more homogeneous smoothing.
      SRBF results in a fully automatic, fast and flexible algorithm potentially
      suitable in wide ranges of speckle noise sizes, for different medical
      applications (IVUS, B-mode, 3-D matrix array US).

PMID- 20691925
TI  - Delivery of chlorambucil using an acoustically-triggered perfluoropentane
      emulsion.
AB  - Ultrasound-mediated delivery systems have mainly focused on microbubble contrast
      agents as carriers of drugs or genetic material. This study uses micron-sized,
      perfluoropentane (PFP) emulsions as carriers of chlorambucil (CHL), a lipophilic
      chemotherapeutic. The release of CHL is achieved via acoustic droplet
      vaporization (ADV), whereby the superheated emulsion is converted into gas
      bubbles using ultrasound. Emulsions were made using an albumin shell and soybean
      oil as the CHL carrier. The ratio of the PFP to soybean oil phases in the
      droplets and the fraction of droplets that vaporize per ultrasound exposure were
      shown to correlate with droplet diameter. A 60-min incubation with the CHL-loaded
      emulsion caused a 46.7% cellular growth inhibition, whereas incubation with the
      CHL-loaded emulsion that was exposed to ultrasound at 6.3 MHz caused an 84.3%
      growth inhibition. This difference was statistically significant (p < 0.01),
      signifying that ADV can be used as a method to substantially enhance drug
      delivery.

PMID- 20691926
TI  - The characterisation of mammalian tissue with 2D relaxation methods.
AB  - The potential of two-dimensional (2D) relaxometry for characterising mammalian
      tissue is explored on samples of liver, kidney (cortex, medulla and ureter) as
      well as cartilage. Significant differences are found between the T(1)-T(2)
      spectra of healthy and diseased human cartilage which suggests that 2D
      relaxometry could have potential use in clinical diagnosis. The effect of
      reducing the recovery delay on the T(1)-T(2) spectrum is explored to try to
      identify the optimum balance between speed and accuracy.

PMID- 20691927
TI  - The introduction of simultaneous dual-source/dual-energy computed tomography (CT)
      scanning is one of the recent technological advances in CT imaging.

PMID- 20691928
TI  - Dual-energy computed tomography for integrative imaging of coronary artery
      disease: principles and clinical applications.
AB  - The introduction of coronary CT angiography (cCTA) has reinvigorated the debate
      whether management of patients with suspected coronary artery disease (CAD)
      should be primarily based on physiological, functional versus anatomical testing.
      Anatomical testing (i.e., cCTA or invasive catheterization) enables direct
      visualization and grading of coronary artery stenoses but has shortcomings for
      gauging the hemodynamic significance of lesions for myocardial perfusion.
      Rest/stress myocardial perfusion imaging (MPI) has been extensively validated for
      assessing the clinical significance of CAD by demonstrating fixed or reversible
      perfusion defects but has only limited anatomical information. There is growing
      evidence that contrast medium enhanced dual-energy cCTA (DECT) has potential for
      the comprehensive analysis of coronary artery morphology as well as changes in
      myocardial perfusion. DECT exploits the fact that tissues in the human body and
      iodine-based contrast media have unique absorption characteristics when
      penetrated with different X-ray energy levels, which enables mapping the iodine
      (and thus blood) distribution within the myocardium. The purpose of this
      communication is to describe the practical application of this technology for the
      comprehensive diagnosis of ischemic heart disease. We examine recent scientific
      findings in the context of current pivotal transitions in cardiovascular disease
      management and demonstrate the potential of cardiac DECT for the integrative
      assessment of patients with known or suspected CAD within a single CT-based
      protocol.

PMID- 20691929
TI  - Dual-energy computed tomography imaging of the aorta after endovascular repair of
      abdominal aortic aneurysm.
AB  - Endovascular repair is increasingly considered a less-invasive alternative to
      open repair of abdominal aortic aneurysm. However, there are still many potential
      complications of endovascular repair, including endoleaks, graft migration,
      thrombosis, and fistula formation. Endoleak is the most common complication for
      which these patients undergo long-term imaging surveillance. Most centers acquire
      computed tomographic (CT) data before contrast administration and during an
      arterial and delayed phase of aortic enhancement after the administration of
      intravenous contrast material to optimize detection of endoleaks. Although this
      technique works well, the downside is significant patient radiation exposure.
      Although the carcinogenic risk of ionizing radiation because of CT exposure is
      low, it has been linked to an increase in the lifelong risk of developing fatal
      cancers. Furthermore, this risk is cumulative and increases with multiple
      radiation exposure, as is true in surveillance after endovascular repair. As a
      result, considerable research is being performed to optimize CT protocols in an
      effort to decrease radiation dose. One such approach is to image these patients
      with recently introduced dual source dual-energy CT system. Using this technique,
      virtual noncontrast data may be generated from a postcontrast acquisition which
      may obviate the routine acquisition of noncontrast acquisition, thus decreasing
      radiation dose. In this article, we discuss the role of dual energy CT imaging in
      evaluation of patients after endovascular repair of abdominal aortic aneurysm.

PMID- 20691930
TI  - Dual-energy lung perfusion computed tomography: a novel pulmonary functional
      imaging method.
AB  - Dual-energy computed tomography (DECT) can be used for visualization of pulmonary
      microvascular contrast material distribution, representing regional perfusion. It
      is performed as DECT angiography and allows for the reconstruction of morphologic
      images as well as of "perfusion maps." The authors of previous studies have shown
      its potential to reliably depict perfusion defects, mainly in the context of
      pulmonary embolism. Also in the diagnostic work-up of other pulmonary diseases,
      there might be additional functional information provided by dual-energy
      acquisition techniques. This review focuses on the physical and technical
      background and the potential clinical value of pulmonary DECT. Technical
      improvements of a second-generation dual-source CT system are elucidated.

PMID- 20691931
TI  - Dual-energy based spectral electronic cleansing in non-cathartic computed
      tomography colonography: an emerging novel technique.
AB  - Computed tomography colonography (CTC) with reduced or without bowel catharsis
      and with fecal tagging has emerged to improve CTC tolerability in patients and
      their subsequent compliance with colorectal cancer screening. With fecal tagging,
      electronic cleansing is performed by postprocessing software that removes
      remnants of contrast material. However, because the technique is threshold based,
      artifacts that lower the image quality and accuracy of the examination may be
      noted. Spectral electronic cleansing, based on dual-energy CT and on material
      specific cleansing, decreases the number of artifacts and improves image quality.
      In this review we describe spectral cleansing with reduced catharsis CTC and
      illustrate its potential benefits.

PMID- 20691932
TI  - Determination of renal stone composition with dual-energy computed tomography: an
      emerging application.
AB  - Urinary tract stone disease is common in the Western world. Nonenhanced computed
      tomography (CT) is the method of choice for stone diagnosis; however, it has a
      limited role in predicting stone type. Knowledge of stone composition is
      currently determined by postoperative assessment of stone fragments. A
      noninvasive tool for accurate characterization of stone composition would improve
      patient management. Dual-energy CT aids in the differentiation among calcium,
      uric acid, and cystine stones. In this review we describe the role of dual-energy
      CT for in vitro and in vivo analysis of urinary stones. We illustrate the
      technique, review the literature, and discuss future directions.

PMID- 20691933
TI  - Dual-energy derived virtual nonenhanced computed tomography imaging: current
      status and applications.
AB  - Radiation exposure is a growing concern, and computed tomography is a main
      contributor to overall radiation dose in American patients. Dual-energy computed
      tomography, by allowing virtual nonenhanced (VNE) imaging, may obviate the need
      for image acquisition during a true nonenhanced phase when multiphase studies are
      needed, thereby reducing radiation exposure. Various groups have reported on the
      technical feasibility and clinical applicability of VNE imaging in the kidney,
      liver, lung, brain, and aorta. VNE is consistently reported to be both feasible
      and clinically relevant, although both hardware and postprocessing capabilities
      currently pose various specific challenges. We review the current state of VNE
      imaging and discuss some challenges to its future application.

PMID- 20691934
TI  - Experience with rufinamide in a pediatric population: a single center's
      experience.
AB  - Rufinamide is a new antiepileptic drug recently approved as adjunctive treatment
      for generalized seizures in Lennox-Gastaut syndrome. We undertook a retrospective
      analysis of 77 patients with refractory epilepsy and receiving rufinamide to
      evaluate the drug's efficacy, tolerability, safety, and dosing schedules. It
      appeared efficacious in diverse epilepsy syndromes, with the highest responder
      rate in focal cryptogenic epilepsies (81.1% of patients with >50% response rate),
      and in diverse seizure types, with the highest responder rate in tonic/atonic and
      partial seizures (48.6% and 46.7% of patients with >50% response rate,
      respectively). Rufinamide was well tolerated: only 13% of patients developed side
      effects necessitating drug withdrawal. These findings suggest that rufinamide may
      possess good efficacy and tolerability, and that its efficacy may extend to
      epilepsy syndromes beyond Lennox-Gastaut, including both partial and generalized
      epilepsy syndromes.

PMID- 20691935
TI  - Recognition of impaired atomoxetine metabolism because of low CYP2D6 activity.
AB  - Ten out of 100 children treated for attention deficit hyperactivity disorder with
      standard doses of atomoxetine were selected by a neurologist for cytochrome P450
      2D6 and cytochrome P450 2C19 genotyping, based on late response (>9 weeks) and
      adverse effects (gastrointestinal problems, sleeping disorders, malaise,
      inactivity, and mood instabilities). After genotyping, eight children were
      confirmed to have compromised cytochrome P450 2D6 activity because of at least
      one nonfunctional or less functional allele. Cytochrome P450 C19 is a minor
      pathway in atomoxetine metabolism and therefore of less importance. Tailored
      therapeutic advice was given to the neurologist. Four children with compromised
      cytochrome P450 2D6 activity responded better after decreasing their atomoxetine
      dose. The other four ceased treatment because of initial adverse effects. These
      cases indicate that compromised atomoxetine metabolism can be recognized, based
      on adverse effects and late response to atomoxetine. Physicians should be aware
      of the typical pattern of adverse effects and late response in atomoxetine
      treatment, possibly indicating compromised cytochrome P450 2D6 activity.
      Cytochrome P450 2D6 genotyping before atomoxetine treatment may be beneficial in
      preventing overdosing or early cessation. Further research is needed to establish
      the cost versus benefit ratio of prospective cytochrome P450 2D6 genotyping in
      atomoxetine treatment.

PMID- 20691936
TI  - Effect of price increase of adrenocorticotropic hormone on treatment practices of
      infantile spasms.
AB  - Intramuscular adrenocorticotropic hormone putatively constitutes the most
      efficacious treatment for infantile spasms. Adrenocorticotropic hormone in the
      United States is an "orphan drug," made by a single manufacturer. The price of
      adrenocorticotropic hormone increased almost 14-fold on August 27, 2007. We
      sought to evaluate the impact of this price increase on treatment practices at
      our institution, using a retrospective chart review of all children with
      infantile spasms treated during 2007-2009. We identified 97 patients whose spasms
      were treated using antiepileptic drugs, and we determined the length of stay for
      those hospitalized to initiate adrenocorticotropic hormone. Patients before the
      price increase were more likely to have been treated with adrenocorticotropic
      hormone as first medication, and were hospitalized 2.2 +/- 0.5 S.D. days for
      initiation. Patients after the price increase were more likely to have been
      treated initially with oral antiepileptic drugs rather than adrenocorticotropic
      hormone (P < 0.002). Those commencing adrenocorticotropic hormone after the price
      increase were hospitalized significantly longer (5.1 +/- 0.6 days S.D., P <
      0.001). Treatment choices need to be evidence-based, but other factors often
      influence them.

PMID- 20691937
TI  - Acute nonparaneoplastic limbic encephalitis in childhood: a case series in Japan.
AB  - Limbic encephalitis not associated with malignancy was investigated in Japanese
      children, with particular focus on clinical features distinct from adult cases.
      Clinical, laboratory, and radiographic findings were studied in pediatric
      nonparaneoplastic limbic encephalitis, based on a literature review and
      questionnaire-based analyses. Analysis of 14 cases revealed the predominance of
      seizure occurrence, disturbance in consciousness, and frequent extralimbic signs.
      The majority manifested antecedent febrile illnesses, suggesting the involvement
      of infection-induced autoimmunity targeted to neuronal antigens. These clinical
      observations indicate a child-specific phenotype of limbic encephalitis. Further
      studies on its immunopathogenesis are needed to determine whether childhood
      limbic encephalitis is a distinct subcategory.

PMID- 20691938
TI  - Impact of steroids on surgical experiences of patients with duchenne muscular
      dystrophy.
AB  - We studied surgical experiences within a regional cohort of patients with
      Duchenne muscular dystrophy, managed at a single center. Records of all patients
      with confirmed Duchenne muscular dystrophy who were born after 1962 were reviewed
      from birth until they reached study endpoints: scoliosis surgery, Achilles tendon
      lengthening, cataract surgery, loss to follow-up, or final follow-up point in
      2009. A survival analysis was used to account for the variable follow-up duration
      within this cohort. By the end of the study period, 28/80 (35.0%) of boys with
      Duchenne muscular dystrophy had undergone spinal surgery, 22/80 (27.5%) had
      experienced Achilles tendon lengthening, and 6/80 (7.5%) had had cataracts
      removed. Moreover, 56.8% of this cohort received steroid therapy (prednisone or
      deflazacort; 95% confidence interval, 43.3-68.8%). Boys who had received steroid
      therapy were significantly less likely to undergo spinal surgery (P = 0.001), but
      were subsequently more likely to require cataract surgery (P = 0.005). Achilles
      tendon lengthening did not seem related to medication exposure. The treatment of
      patients with Duchenne muscular dystrophy with steroids significantly modified
      their surgical experience.

PMID- 20691939
TI  - Ratios of nine risk factors in children with recurrent febrile seizures.
AB  - Febrile seizures are the most common convulsive disorder of childhood, with a
      recurrence probability of 33%. The aim of the study was to determine the risk
      factors for recurrence of febrile seizures in children. In this descriptive,
      cross-sectional study, nine risk factors of recurrence of febrile seizures were
      investigated in 259 children with febrile seizures: (1) sex; (2) domicile; (3)
      income level; (4) family history of febrile seizures; (5) family history of
      epilepsy; (6) level of fever; (7) duration of fever; (8) type of seizure, simple
      vs complex; and (9) age at seizure onset. The risk factors were compared for 119
      children with isolated febrile seizures (45.9% of the total) and 140 children
      with two or more febrile seizure recurrences (54.1%). Among the patients with and
      without recurrent febrile seizures, 32% and 18% were domiciled in nonurban areas,
      respectively (P = 0.012). There was a family history of febrile seizures in 57%
      and 44% of cases with and without recurrent febrile seizures, respectively (P =
      0.031). According to the logistic regression analysis, a family history of
      febrile seizures was a risk factor that affected recurrence (P = 0.018; odds
      ratio OR = 1.933; 95% confidence interval CI = 1.121-3.333). We also found that
      domicile (P = 0.001) and income (P = 0.013) were risk factors for recurrence. A
      family history of epilepsy was not a significant risk factor (P = 0.129; OR =
      2.110; 95% CI = 0.804-5.539).

PMID- 20691940
TI  - Clinical manifestations in children with mitochondrial diseases.
AB  - Mitochondrial diseases comprise a group of complex and heterogeneous genetic
      disorders. Variable clinical features present a major challenge in pediatric
      diagnoses. From January 1984-June 2009, 69 patients were diagnosed with either
      syndromic mitochondrial diseases or nonsyndromic mitochondrial diseases. Clinical
      manifestations, laboratory findings, and histopathologic results differentiating
      syndromic from nonsyndromic mitochondrial diseases were analyzed by chi(2) test,
      with cutoff significance at P = 0.05. The commonest clinical manifestation
      involved central nervous system signs (88.4%). A comparison of central nervous
      system signs in syndromic vs nonsyndromic mitochondrial diseases revealed
      significant differences in terms of headache, external ocular motility, and apnea
      (P < 0.05). A comparison of organ systems revealed a significant difference for
      signs of the cardiovascular system. Elevated initial blood lactate levels were
      evident in 40.6% of patients, and 84.8% produced abnormal results after oral
      glucose challenge. Ragged red fibers were observed in 51.6% of patients. The
      positive rate of mitochondrial gene mutation was 27.5%. Age and disease were
      directly related: the younger the age at initial disease onset, the higher the
      frequency of mortality and morbidity. Notorious variability in the presentation
      of mitochondrial diseases exists in all pediatric subspecialties. Greater
      familiarity with those signs will facilitate more accurate diagnoses.

PMID- 20691941
TI  - Restricted diffusion in the corpus callosum in hypoxic-ischemic encephalopathy.
AB  - Restricted diffusion within the splenium of the corpus callosum was described in
      various conditions, but is not a prominent finding in magnetic resonance imaging
      after neonatal hypoxic-ischemic encephalopathy. Perinatal characteristics were
      reviewed in 42 term neonates with hypoxic-ischemic encephalopathy treated with
      selective head cooling. Neonatal images of 34 infants were reviewed. Ten of 34
      (29%) infants demonstrated restricted diffusion changes within the splenium of
      the corpus callosum, with a significantly higher incidence of death or severe
      developmental delay, compared with infants without changes in the splenium of the
      corpus callosum (n = 24) (P = 0.002). The positive predictive value of changes in
      the splenium of the corpus callosum regarding poor outcomes or death was 90%.
      Changes in the splenium of the corpus callosum were also associated with lower
      birth weights, larger base deficits in cord arterial gas, and more severe
      encephalopathy during enrollment in selective head cooling. Restricted diffusion
      within the splenium of the corpus callosum of term infants with hypoxic-ischemic
      encephalopathy is often associated with extensive brain injury, and in these
      circumstances appears to be an early neuroradiologic marker of adverse neurologic
      outcomes.

PMID- 20691942
TI  - Reversible posterior leukoencephalopathy induced by cancer chemotherapy.
AB  - Reversible posterior leukoencephalopathy, defined by both clinical and
      neuroimaging findings, can affect children receiving chemotherapy. The syndrome
      is characterized by hypertension, alterations in mental status, seizures,
      hallucinations, and acute visual changes and is associated with abnormalities
      seen in magnetic resonance imaging of symmetric white matter lesions, especially
      in the parietal and occipital lobes. The etiology of reversible posterior
      leukoencephalopathy is as yet unknown. Presented here are four cases of
      reversible posterior leukoencephalopathy induced by chemotherapy, with a brief
      review of the literature and consideration of possible mechanisms. A diagnosis of
      reversible posterior leukoencephalopathy should be considered when patients
      receiving cancer chemotherapy suddenly develop hypertension followed by
      neurologic complications, especially if presenting with seizures.

PMID- 20691943
TI  - Facial capillary malformation and Dyke-Davidoff-Masson syndrome.
AB  - Described here is the case of a girl with a reticulated capillary malformation on
      the right side of her face, along with Dyke-Davidoff-Masson syndrome, as
      evidenced by microphthalmia and severe associated anomalies in the right eye, and
      right cerebral hemispheric atrophy and cerebral arteries malformations. Capillary
      malformations are a novel finding for children with Dyke-Davidoff-Masson
      syndrome.

PMID- 20691944
TI  - Zonisamide ameliorates symptoms of secondary paroxysmal dystonia.
AB  - A number of medications have been used with varying success to treat the symptoms
      of generalized, focal, and paroxysmal dyskinesias; these agents include
      anticonvulsant, benzodiazepine, neuroleptic, dopaminergic, dopamine antagonist,
      and carbonic anhydrase inhibitor types. The carbonic anhydrase inhibitor drug
      group is best represented by acetazolamide, which has been widely applied in the
      treatment of paroxysmal dyskinesias. Zonisamide, which has several putative
      pharmacologic mechanisms of action, is a member of the carbonic anhydrase
      inhibitor drug group. Zonisamide was chosen for treatment of secondary paroxysmal
      dystonia in a patient with pyruvate dehydrogenase deficiency (case 1) and in two
      patients with neonatal hemochromatosis and family history of neonatal
      hemochromatosis (cases 2 and 3). Although zonisamide ameliorated the symptoms of
      secondary paroxysmal dystonia in these three patients, the precise biochemical
      mechanism remains unclear, and further studies are needed to substantiate and
      explain this finding.

PMID- 20691945
TI  - Developmental disability: duplication of zinc finger transcription factors 673
      and 674.
AB  - The past decade has witnessed a tremendous increase in our ability to identify
      precise genetic etiologies of developmental delay and intellectual disability.
      Mutations in various transcription factors were found in patients with
      intellectual disability. Specifically, the importance of a subgroup of
      transcription factors containing zinc finger motifs have been increasingly
      recognized in developmental delay and intellectual disability. We present a
      patient with intellectual disability in whom the duplication of two genes, ZNF673
      and ZNF674, was identified through array-based comparative genomic hybridization.
      Our report reinforces the role of zinc finger transcription factors in cognitive
      development. Furthermore, it illustrates that not only deletions, but
      duplications, can cause developmental delay and intellectual disability.

PMID- 20691946
TI  - Benign myoclonic epilepsy of infancy evolving to Jeavons syndrome.
AB  - Benign myoclonic epilepsy of infancy is a rare idiopathic generalized epileptic
      syndrome occurring below the age of 3 years. Although benign outcome is presumed,
      some recent studies suggest less favorable outcome. A 14-year-old boy had a
      history of repeated episodes of myoclonic jerks of the shoulders and upper limbs
      in infancy (age 5 months). An ictal electroencephalogram indicated generalized
      spike-wave discharges associated with the myoclonic seizures, and the diagnosis
      of benign myoclonic epilepsy of infancy was made. Valproate treatment resulted in
      control of the myoclonic seizures, and the drug was withdrawn when the patient
      was 5 years of age. At the age of 10, he presented with episodes of eyelid jerks
      associated with brief lapses in concentration triggered by sunlight.
      Electroencephalography revealed photosensitivity and a pattern of eye-closure
      sensitivity. These features were compatible with the diagnosis of eyelid
      myoclonia with absences, or Jeavons syndrome. Lamotrigine eliminated the
      seizures. The evolution of benign myoclonic epilepsy of infancy to eyelid
      myoclonia with absences has been reported in one other case. A possible continuum
      of myoclonic epileptic syndromes, mediated by a common genetic abnormality,
      suggests the need for longer monitoring of patients with benign myoclonic
      epilepsy of infancy.

PMID- 20691947
TI  - Cortical hypometabolism demonstrated by PET in relapsing NMDA receptor
      encephalitis.
AB  - N-methyl-d-aspartate (NMDA) receptor encephalitis is a newly defined type of
      autoimmune encephalitis. Two girls (age 3 years, case 1, and 7 years, case 2)
      with relapsing NMDA receptor encephalitis each had the classic clinical features
      of encephalopathy, movement disorders, psychiatric symptoms, seizures, insomnia,
      and mild autonomic dysfunction. Both patients had persistent neuropsychiatric
      disability, despite immune therapies. Positron emission tomography (PET) scans
      were performed during clinical relapse at 6 weeks (case 1) and 5 months (case 2).
      In both cases, the scans demonstrated reduced fluorodeoxyglucose metabolism in
      the cerebral cortex, with the temporal regions being most affected. PET imaging
      was more sensitive than magnetic resonance imaging in these patients. In
      contrast, the one previous report of acute NMDA receptor encephalitis indicated
      cortical hypermetabolism. Thus, NMDA receptor encephalitis may be associated with
      variable PET findings, possibly dependent upon the timing of the study, or other
      factors. Future studies should investigate whether cortical hypometabolism is
      associated with a relapsing course, and whether it is predictive of a poorer
      outcome in NMDA receptor encephalitis.

PMID- 20691948
TI  - Nonketotic hyperglycinemia: proposal of a diagnostic and treatment strategy.
AB  - Early myoclonic encephalopathy presents neonatally with fragmented myoclonus and
      a suppression-burst electroencephalography pattern. We describe a newborn boy
      with early myoclonic encephalopathy caused by nonketotic hyperglycinemia. He
      presented with severe hypotonia, progressive apneic episodes, and erratic
      myoclonus. Screening of deletions in GLDC, using the multiplex ligation-dependent
      probe amplification method, and a (13)C breath test confirmed the diagnosis of
      nonketotic hyperglycinemia. Treatment with the N-methyl-d-aspartate receptor
      antagonist ketamine exerted dramatic suppressive effects on his seizures, and
      ameliorated his clinical status.

PMID- 20691949
TI  - Venous sinus thrombosis and consumptive coagulopathy: a role for heparin?
AB  - Cerebral venous sinus thrombosis is a relatively rare but serious condition, more
      commonly affecting children and pregnant women. It can be precipitated by
      dehydration. Despite the frequent coexistence of hemorrhage in venous infarcts of
      patients, clinical trials in adults recommended the use of anticoagulation. No
      randomized, clinical trials exist in the pediatric age group. Rarely, consumptive
      coagulopathy is reported to coexist with cerebral venous sinus thrombosis. We
      report on a child with venous sinus thrombosis and consumptive coagulopathy
      developing after routine tonsillectomy and its successful management with
      anticoagulation.

PMID- 20691950
TI  - Steroid profiling and analytics: going towards sterome.

PMID- 20691951
TI  - Transmission of toxoplasmosis (Toxoplasma gondii) by foods.
AB  - Protozoan foodborne diseases are generally underrecognized. Toxoplasma gondii is
      the causative agent of toxoplasmosis, one of the most prevalent parasitic
      infections to humans and domestic animals. The most likely source of T. gondii
      occurring through food is the consumption of raw or undercooked meat contaminated
      with tissue cysts. Sporulated T. gondii oocysts, from the feces of infected cats,
      present in the environment are a potential source of infection. The ingestion of
      water contaminated with oocysts and the eating of unwashed raw vegetables or
      fruits were identified as an important risk factor in most epidemiological
      studies. This review presents information and data to show the importance of T.
      gondii transmission by foods.

PMID- 20691952
TI  - The importance of dietary protein in human health: combating protein deficiency
      in sub-Saharan Africa through transgenic biofortified sorghum.
AB  - Child malnutrition is increasing in Africa. Protein deficiency is an important
      cause since protein is essential for both growth and maintenance of muscle mass.
      Sorghum is a major staple food in Africa on account of its hardiness as a crop.
      However, sorghum protein is very deficient in the indispensable amino acid lysine
      and on cooking has poor protein digestibility. This results in sorghum having a
      very low Protein Digestibility Corrected Amino Acid Score (PDCAAS). The Africa
      Biofortified Sorghum project, a Grand Challenges in Global Heath project, is
      undertaking research to biofortify sorghum in terms of protein and micronutrient
      quality using genetic engineering. Lysine and protein digestibility have been
      improved by suppression of synthesis of the kafirin storage proteins. Transgenic
      biofortified sorghum has double the PDCAAS of conventional sorghum. This
      improvement should enable a young child to meet most of its protein and energy
      requirements from biofortified sorghum porridge. This together with the
      improvement in micronutrients could provide the basis of a sustainable and
      broadly comprehensive solution to child malnutrition in many African countries.

PMID- 20691953
TI  - Clostridium difficile: its potential as a source of foodborne disease.
AB  - Clostridium difficile has been recognized as an important human pathogen for
      several decades, but its importance as an agent of animal disease was established
      only recently. The number of reports on C. difficile in food is rising, but the
      findings vary among studies. In North America, the prevalence of contamination in
      retail meat and meat products ranges from 4.6% to 50%. In European countries, the
      percentage of C. difficile positive samples is much lower (0-3%). This chapter
      summarizes current data on association of C. difficile with different foods and
      the difficulties associated with isolation of the organism, and discusses the
      potential of C. difficile as a food-transmitted pathogen.

PMID- 20691954
TI  - Escherichia coli O157:H7: recent advances in research on occurrence,
      transmission, and control in cattle and the production environment.
AB  - Escherichia coli O157:H7 is a zoonotic pathogen that is an important cause of
      human foodborne and waterborne disease, with a spectrum of illnesses ranging from
      asymptomatic carriage and diarrhea to the sometimes fatal hemolytic uremic
      syndrome. Outbreaks of E. coli O157:H7 disease are often associated with
      undercooked beef, but there are other sources of transmission, including water,
      produce, and animal contact, which can often be linked directly or indirectly to
      cattle. Thus, preharvest control of this pathogen in cattle production should
      have a large impact on reducing the risk of human foodborne illness. In this
      review, we will summarize preharvest research on E. coli O157:H7 in cattle and
      the production environment, focusing on factors that may influence the
      transmission, prevalence, and levels of this pathogen, such as season, diet, high
      level shedders, and animal stress. In addition, we will discuss recent research
      on the reduction of this pathogen in cattle production, including vaccination,
      probiotics, bacteriophage, and manure treatments.

PMID- 20691955
TI  - Fish gelatin.
AB  - Gelatin is a multifunctional ingredient used in foods, pharmaceuticals,
      cosmetics, and photographic films as a gelling agent, stabilizer, thickener,
      emulsifier, and film former. As a thermoreversible hydrocolloid with a narrower
      gap between its melting and gelling temperatures, both of which are below human
      body temperature, gelatin provides unique advantages over carbohydrate-based
      gelling agents. Gelatin is mostly produced from pig skin, and cattle hides and
      bones. Some alternative raw materials have recently gained attention from both
      researchers and the industry not just because they overcome religious concerns
      shared by Jews and Muslims but also because they provide, in some cases,
      technological advantages over mammalian gelatins. Fish skins from a number of
      fish species are among the other sources that have been comprehensively studied
      as sources for gelatin production. Fish skins have a significant potential for
      the production of high-quality gelatin with different melting and gelling
      temperatures over a much wider range than mammalian gelatins, yet still have a
      sufficiently high gel strength and viscosity. Gelatin quality is industrially
      determined by gel strength, viscosity, melting or gelling temperatures, the water
      content, and microbiological safety. For gelatin manufacturers, yield from a
      particular raw material is also important. Recent experimental studies have shown
      that these quality parameters vary greatly depending on the biochemical
      characteristics of the raw materials, the manufacturing processes applied, and
      the experimental settings used for quality control tests. In this review, the
      gelatin quality achieved from different fish species is reviewed along with the
      experimental procedures used to determine gelatin quality. In addition, the
      chemical structure of collagen and gelatin, the collagen-gelatin conversion, the
      gelation process, and the gelatin market are discussed.

PMID- 20691956
TI  - Membrane proteins as drug targets. Preface.

PMID- 20691957
TI  - Inverse agonism at serotonin and cannabinoid receptors.
AB  - Contemporary receptor theory was developed to account for the existence of
      constitutive activity, as defined by the presence of receptor signaling in the
      absence of any ligand. In vitro studies with a variety of cell types have
      revealed the existence of constitutive activity and inverse agonism at a large
      number of receptors and also additional complexities of ligand-receptor
      interactions. Thus, ligands acting at a constitutively active receptor can act as
      agonists, antagonists, and/or inverse agonists, and these pharmacological
      characteristics can differ for an individual ligand depending upon the receptor
      response measured and the physiological state of the system under study. Studies
      with a variety of cell types have established that the serotonin 5-HT(2A) and 5
      HT(2C) receptors and the cannabinoid CB1 receptor demonstrate constitutive
      activity and inverse agonism in vitro. Serotonin and cannabinoid receptors are
      involved in a large number of physiological and behavioral functions. The
      possible existence of constitutive activity and inverse agonism at these
      receptors in vivo would provide new avenues for drug development. Recent studies
      have provided compelling evidence that both the serotonin 5-HT(2A) and 5-HT(2C)
      receptors and cannabinoid CB1 receptor demonstrate inverse agonism and
      constitutive activity also in vivo. This chapter describes our current knowledge
      of constitutive activity in vitro and then examines the evidence for constitutive
      activity in vivo.

PMID- 20691958
TI  - G protein-coupled receptor heteromers as new targets for drug development.
AB  - We now have a significant amount of experimental evidence that indicates that G
      protein-coupled receptor (GPCR) oligomerization, including homo- and
      heteromerization, is a general phenomenon. Receptor heteromers possess unique
      biochemical characteristics that are demonstrably different from those of its
      individual units. These properties include allosteric modulation(s) between
      units, changes in ligand recognition, G protein-coupling and trafficking. The
      discovery of GPCR oligomers have been related to the parallel discovery and
      application of a variety of resonance energy transfer (RET) techniques, such as
      bioluminescence, fluorescence and sequential RET (BRET, FRET and SRET,
      respectively), time-resolved FRET (T-FRET) and fluorescence recovery after
      photobleaching (FRAP) microscopy. However, RET techniques are difficult to
      implement in native tissues. For receptor heteromers, indirect approaches, such
      as the determination of a unique biochemical characteristic ("biochemical
      fingerprint"), permit their identification in native tissues and their use as
      targets for drug development. Dopamine and opioid receptor heteromers are the
      focus of intense research which is related to the possible multiple applications
      of their putative ligands in pathological conditions, which include basal ganglia
      disorders, schizophrenia and drug addiction.

PMID- 20691959
TI  - Receptor activity modifying proteins and their potential as drug targets.
AB  - The receptor activity modifying proteins (RAMPs) are a family of membrane
      proteins that interact with some G protein-coupled receptors (GPCRs) to regulate
      their function. RAMPs can alter GPCR pharmacology and can regulate their
      signaling as well as trafficking to and from the cell surface. GPCRs have been
      successfully exploited as drug targets for many years. RAMPs therefore provide a
      new avenue for drug development, offering opportunities for regulating the
      function of therapeutically relevant RAMP-interacting GPCRs. RAMPs could be
      directly targeted themselves or advantage could be taken of the unique RAMP/GPCR
      interfaces for generating more selective drugs.

PMID- 20691960
TI  - Regulators of G protein signaling proteins as targets for drug discovery.
AB  - Signaling via G-protein-coupled receptors (GPCRs) is central for the function of
      biological systems. Many clinically used drugs target GPCRs directly or target
      molecules involved in GPCR signaling. As an alternative to targeting receptors
      directly, one could modulate signaling cascades downstream of receptor
      activation. In recent years, there has been substantial interest in a family of
      proteins called regulators of G protein signaling (RGS) proteins. They modulate
      GPCR signaling by accelerating GTP hydrolysis on active Galpha subunits, thereby
      reducing the amplitude and duration of signaling. Modulating RGS activity would
      be a useful strategy to control GPCR signaling. An RGS inhibitor would be
      expected to enhance GPCR signaling and could do so in a tissue- or pathway
      specific manner. Apart from the central GAP (GTPase accelerating protein)
      activity, many RGS proteins also have other functions like regulating protein
      protein interactions, subcellular localization of signaling molecules, and
      protein translation. It is clear that these proteins serve important functions in
      a number of physiological and pathophysiological processes, and they are emerging
      as potential drug targets. This chapter gives an overview of what is currently
      known about biological functions of RGS proteins based on in vivo and in vitro
      data. We also summarize the current status in targeting RGS proteins in drug
      discovery.

PMID- 20691962
TI  - The T1R2/T1R3 sweet receptor and TRPM5 ion channel taste targets with therapeutic
      potential.
AB  - Taste signaling is a critical determinant of ingestive behaviors and thereby
      linked to obesity and related metabolic dysfunctions. Recent evidence of taste
      signaling pathways in the gut suggests the link to be more direct, raising the
      possibility that taste receptor systems could be regarded as therapeutic targets.
      T1R2/T1R3, the G protein coupled receptor that mediates sweet taste, and the
      TRPM5 ion channel have been the focus of discovery programs seeking novel
      compounds that could be useful in modifying taste. We review in this chapter the
      hypothesis of gastrointestinal taste signaling and discuss the potential for
      T1R2/T1R3 and TRPM5 as targets of therapeutic intervention in obesity and
      diabetes. Critical to the development of a drug discovery program is the creation
      of libraries that enhance the likelihood of identifying novel compounds that
      modulate the target of interest. We advocate a computer-based chemoinformatic
      approach for assembling natural and synthetic compound libraries as well as for
      supporting optimization of structure activity relationships. Strategies for
      discovering modulators of T1R2/T1R3 and TRPM5 using methods of chemoinformatics
      are presented herein.

PMID- 20691961
TI  - Escorts take the lead molecular chaperones as therapeutic targets.
AB  - The functional and physiological diversity of transmembrane receptors results
      from factors that influence the pharmacology, signaling, and trafficking of these
      receptors. Receptor mutations and other modifications may lead to misfolding,
      intracellular retention, and ineffective signaling of transmembrane receptors.
      The importance of such mutations is highlighted by the fact that various diseases
      have been linked to mutations that lead to ineffective signaling of these
      receptors, resulting from the retention of receptors in intracellular
      compartments. Studies focused on understanding the regulation of trafficking and
      cell surface expression of newly synthesized receptors have highlighted molecular
      chaperones as key regulators of receptor maturation and sorting. In this chapter,
      we discuss the functions of molecular chaperones in the regulation of seven
      transmembrane-containing G-protein-coupled receptor function and trafficking and
      explore ways in which chaperones can serve as novel therapeutic targets.

PMID- 20691963
TI  - Challenges and approaches for assay development of membrane and membrane
      associated proteins in drug discovery.
AB  - In addition to its role as a barrier between the cytoplasm and the extracellular
      milieu, the cell membrane is a scaffold for a diverse collection of receptors and
      enzymes. The organization afforded by this scaffold serves to ensure an efficient
      interaction between the components of the membrane. The desire to maintain this
      organization in solution is a challenge for the appropriate interrogation of
      these biochemical components. This chapter will discuss strategies that allow
      biochemical analysis of membrane-associated enzymes within standard biochemical
      reactions. The advantages of these screening strategies in identifying valuable
      compounds from compound libraries and in understanding the intricacies of complex
      multiprotein complexes (i.e., chemotaxis) will be discussed.

PMID- 20691964
TI  - Preoperative predictors of death in twin-to-twin transfusion syndrome treated
      with laser ablation of placental anastomoses.
AB  - OBJECTIVE: To determine preoperative predictive factors for donor and recipient
      death after laser ablation of placental vessels in twin-to-twin transfusion
      syndrome. STUDY DESIGN: Retrospective analysis of North American Fetal Therapy
      Network center laser procedures, 2002-2009. Factors associated with donor and
      recipient death were identified by regression analysis. RESULTS: There were 466
      patients from 8 centers. Factors significantly associated with donor fetal death
      were low donor estimated fetal weight (odds ratio [OR], 0.69; 95% confidence
      interval [CI], 0.55-0.87) and reversed end diastolic velocity in the umbilical
      artery (OR, 4.0; 95% CI, 1.54-10.2); for recipient fetal death-low recipient
      estimated fetal weight (OR, 0.65; 95% CI, 0.44-0.95), recipient reversed "a" wave
      in the ductus venosus (OR, 2.39; 95% CI, 1.27-4.51) and hydrops (OR, 3.7; 95% CI,
      1.1-12.7); for recipient neonatal death-low donor estimated fetal weight (OR,
      0.54; 95% CI, 0.30-0.95), high recipient estimated fetal weight (OR, 1.55; 95%
      CI, 1.06-2.26) and recipient reversed end diastolic velocity in the umbilical
      artery (OR, 7.8; 95% CI, 1.03-59.3). CONCLUSION: Preoperative findings predict
      fetal and neonatal demise in twin-to-twin transfusion syndrome treated with laser
      therapy.

PMID- 20691965
TI  - Protein:creatinine ratio in uncomplicated twin pregnancy.
AB  - OBJECTIVE: Women with twin pregnancies may have higher rates of isolated
      proteinuria than do those with singletons. We compared protein-to-creatinine
      (P:C) ratios longitudinally through gestation in uncomplicated twin and singleton
      pregnancies. STUDY DESIGN: P:C ratios were compared at 3 times points in 102 (51
      twins, 51 singletons) healthy gravid patients who did not have preeclampsia
      develop, using linear and logistic regression techniques. RESULTS: P:C ratio
      increased significantly over gestation in all patients. This increase was
      significantly greater in twins than in singletons. The odds of P:C ratio >0.19
      was 3.5 times higher in twins between 34 and 38 weeks. CONCLUSION: Women with
      uncomplicated twin pregnancies have greater protein excretion as measured by P:C
      ratios than do those with singletons. In early pregnancy, protein excretion is
      similar, but it diverges significantly by the latter third trimester. We suggest
      that normal values for proteinuria in twins may differ from those in singletons,
      and warrant further evaluation.

PMID- 20691966
TI  - [Weight change, cardiometabolic risk and the impact of antidiabetic medications
      in type 2 diabetic patients].
AB  - In the first part of this review article, the prognostic impact of weight and
      weight changes in terms of clinical outcomes and metabolic control is reviewed,
      through the analysis of the results of several large cohorts and prospective
      studies of diabetic patients followed in "real world" settings. The second part
      of the review focuses on the impact of antidiabetic medications on weight,
      emphasising the importance of a comprehensive approach, taking into account
      weight, in the management of diabetic patients.

PMID- 20691967
TI  - Noninvasive diagnosis of pulmonary hypertension using heart sound analysis.
AB  - Right-heart catheterization is the most accurate method for measuring pulmonary
      artery pressure (PAP). It is an expensive, invasive procedure, exposes patients
      to the risk of infection, and is not suited for long-term monitoring situations.
      Medical researchers have shown that PAP influences the characteristics of heart
      sounds. This suggests that heart sound analysis is a potential method for the
      noninvasive diagnosis of pulmonary hypertension. We describe the development of a
      prototype system, called PHD (pulmonary hypertension diagnoser), that implements
      this method. PHD uses patient data with machine learning algorithms to build
      models of how pulmonary hypertension affects heart sounds. Data from 20 patients
      were used to build the models and data from another 31 patients were used as a
      validation set. PHD diagnosed pulmonary hypertension in the validation set with
      77% accuracy and 0.78 area under the receiver-operating-characteristic curve.

PMID- 20691968
TI  - Role of the precentral gyrus of the insula in complex articulation.
AB  - Previous research has suggested that the left anterior insula, specifically the
      superior precentral gyrus of the insula (SPGI), is a critical brain region for
      the coordination of complex articulatory movements. However, previous studies
      have not determined which articulatory factors are specifically dependent on this
      brain region. In the current study, 33 left hemisphere stroke patients with
      varying degrees of speech impairment were asked to perform multiple repetitions
      of single words that varied along three separate dimensions: number of syllables,
      degree of articulatory travel (i.e., change between places of articulation for
      consonants), and presence/absence of an initial consonant cluster. The role of
      the SPGI in performance across the three conditions was determined using voxel
      based lesion symptom mapping (VLSM), a statistical approach to lesion analysis
      that does not require separating patients based on lesion site or symptom
      profile. Rather, continuous performance data are entered, along with lesions
      reconstructed in normalized space. Based on preliminary analyses, there was
      adequate power to detect differences in the SPGI, which was the focus of our
      predictions. We found that the SPGI was critical for performance on the
      articulation task across all three conditions, namely, when words were multi
      syllabic, required a high degree of travel, or involved an initial consonant
      cluster. As a control, we also generated a VLSM map for articulation of words
      with minimal articulatory complexity (i.e., single-syllable words with no initial
      cluster and a minimal change in place of articulation). In this case, the SPGI
      was not implicated. The current results suggest that the left SPGI is a critical
      area for intra- and inter-syllabic coordination of complex articulatory
      movements, prior to end-stage execution of speech commands.

PMID- 20691969
TI  - Mercury and polychlorinated biphenyls in Asian market fish: a response to results
      from mercury biomonitoring in New York City.
AB  - In 2004, the New York City (NYC) Health and Nutrition Examination Survey measured
      the highest blood mercury levels in Asian and foreign-born Chinese demographic
      groups. Fish consumption was the strongest predictor of exposure. The survey did
      not inquire about consumption of individual species, and subsequent visits to
      fish markets serving the Asian community suggested that many popular species lack
      contaminant data. Our objective was to supplement existing information on
      contaminants in commercial fish by collecting data on species present in markets
      serving the Asian community. We measured total mercury and the sum of 101
      polychlorinated biphenyl (PCB) congeners in 282 individual specimens of 19
      species or products from retail fish markets in Chinese neighborhoods in NYC.
      Species were selected based on their volume in the market, and an absence or
      insufficiency of national data on mercury levels. PCBs were measured because they
      are also contaminants of concern. All measurements were made on a wet weight
      basis on whole fillets (with skin) or products (drained of liquid). Mean mercury
      levels ranged from below the limit of detection (0.004microg/g) in tilapia to
      0.229microg/g in tilefish. The highest mercury level (1.150microg/g) was measured
      in a tilefish specimen, and mercury levels in tilefish increased with the
      specimen size. Mean PCB levels ranged from 1ng/g in red snapper to 98ng/g in
      buffalo carp. The highest PCB levels were measured in a buffalo carp (469ng/g)
      and a yellow croaker (495ng/g). Species-specific differences in PCB levels
      accounted for only 6.3% of total variability, in contrast with 39.2% for mercury.
      Although we did not measure high mean mercury levels in the species we sampled,
      frequent consumption of fish with low to moderate levels can also elevate blood
      mercury. The data we collected can be used to guide fish consumption in Asian
      communities. However, risk-benefit trade-offs also need to be considered.

PMID- 20691971
TI  - Elevated serum lipoprotein(a) as a potential predictor for combined intracranial
      and extracranial artery stenosis in patients with ischemic stroke.
AB  - OBJECTIVES: Despite compelling evidence of lipoprotein(a) [Lp(a)] as a risk
      factor for ischemic stroke, its underlying mechanism remains unclear. Our aim is
      to investigate whether serum Lp(a) level is associated with the extent and
      location of cerebral steno-occlusive lesions, and with large artery
      atherosclerotic (LAA) stroke in Korean patients. METHODS: We analyzed data
      prospectively collected over a 3-year period on consecutive patients with stroke
      or TIA. Based on an angiographic study, a total of 1012 patients were classified
      into four subtypes: non-cerebral stenosis (n=654), intracranial stenosis (n=198),
      extracranial carotid stenosis (n=86), and combined intracranial and extracranial
      carotid stenosis (n=74). Independent associations of Lp(a) levels with the extent
      and location of cerebral stenosis were evaluated, and Lp(a) levels of subtypes by
      the TOAST criteria were compared. RESULTS: Lp(a) levels of LAA stroke were
      significantly higher than those of the other four stroke mechanisms. Patients
      with more advanced intracranial (p=0.001) and extracranial carotid stenoses
      (p=0.001) tended to have higher Lp(a) levels. In multiple regression analysis,
      the third Lp(a) quartile was the strongest risk factor for isolated intracranial
      (OR 3.36, 95% CI 1.77-6.37) or extracranial stenosis (OR 4.82, 95% CI 1.96
      11.88), whereas the fourth Lp(a) quartile was the most powerful predictor for
      combined intracranial and extracranial carotid stenosis (OR 4.98, 95% CI 1.92
      12.91). CONCLUSIONS: Our results indicate that greatly elevated Lp(a) levels are
      associated with LAA stroke and extensive burden of cervicocerebral steno
      occlusive lesions, which might offer indirect evidence of proatherothrombogenic
      role of Lp(a) in ischemic stroke.

PMID- 20691972
TI  - Muscle contributions to propulsion and support during running.
AB  - Muscles actuate running by developing forces that propel the body forward while
      supporting the body's weight. To understand how muscles contribute to propulsion
      (i.e., forward acceleration of the mass center) and support (i.e., upward
      acceleration of the mass center) during running we developed a three-dimensional
      muscle-actuated simulation of the running gait cycle. The simulation is driven by
      92 musculotendon actuators of the lower extremities and torso and includes the
      dynamics of arm motion. We analyzed the simulation to determine how each muscle
      contributed to the acceleration of the body mass center. During the early part of
      the stance phase, the quadriceps muscle group was the largest contributor to
      braking (i.e., backward acceleration of the mass center) and support. During the
      second half of the stance phase, the soleus and gastrocnemius muscles were the
      greatest contributors to propulsion and support. The arms did not contribute
      substantially to either propulsion or support, generating less than 1% of the
      peak mass center acceleration. However, the arms effectively counterbalanced the
      vertical angular momentum of the lower extremities. Our analysis reveals that the
      quadriceps and plantarflexors are the major contributors to acceleration of the
      body mass center during running.

PMID- 20691973
TI  - Fabrication of superporous agarose beads for protein adsorption: effect of CaCO3
      granules content.
AB  - Agarose gels were fabricated by water-in-oil emulsification with the addition of
      CaCO(3) granules at 8-16 wt%. Thus agarose beads of different superporosities
      were produced after dissolving the solid porogen. The superporous agarose (SA)
      and homogeneous agarose gels were double cross-linked and modified with
      diethylaminoethyl chloride to produce anion exchangers. We have proposed to use a
      superporous replica (porous titania microspheres) to examine the superporous
      structure and pore size distribution of the soft gel. The replica was prepared
      with the agarose gel entrapping CaCO(3) granules by a sol-gel-templating method.
      It was found that the superpores created by CaCO(3) granules were uniformly
      distributed and ranged from 0.95 microm to 1.33 microm. The physical properties
      of the gels were significantly affected by the porogen content. Importantly, by
      increasing the solid porogen to 12 wt%, the bed permeability and effective
      porosity increased about 48% and 33%, respectively. Further increase in the
      porogen to 16 wt% led to a decrease of the mechanical strength. With increasing
      superpores in the beads, the dynamic adsorption capacity of the packed columns
      increased obviously at 305-916 cm/h. Besides, the column efficiency changed less
      with increasing flow velocity up to 1200 cm/h. It was concluded that the use of
      12 wt% CaCO(3) granules in agarose solution was beneficial for the fabrication of
      the SA gel with good mechanical stability and promising performance for protein
      chromatography.

PMID- 20691975
TI  - High-temperature solvent stability of sol-gel germania triblock polymer coatings
      in capillary microextraction on-line coupled to high-performance liquid
      chromatography.
AB  - Germania-based sol-gel organic-inorganic hybrid coatings were prepared for on
      line coupling of capillary microextraction with high-performance liquid
      chromatography. For this, a germania-based sol-gel precursor, tetra-n
      butoxygermane and a hydroxy-terminated triblock copolymer, poly(ethylene oxide)
      block-poly(propylene oxide)-block-poly(ethylene oxide) were used. These sol-gel
      germania triblock polymer coatings were chemically anchored to the inner walls of
      a fused silica capillary (0.25 mm I.D.) in course of its evolution from the sol
      solution. Scanning electron microscopy images of the sol-gel germania triblock
      polymer coating were obtained to estimate the coating thickness. For the first
      time, the analyte distribution constants between a sol-gel germania organic
      inorganic hybrid coating and the samples (K(cs)) were determined. For a variety
      of analytes from different chemical classes, including polycyclic aromatic
      hydrocarbons (PAHs), ketones, alcohols, phenols and amines, the K(cs) values
      ranged from 8.1 x 10(1) to 5.6 x 10(4). Also, for the first time, the stability
      of the sol-gel germania-based coating in high-temperature reversed-phase solvent
      environment was evaluated. The sol-gel germania triblock polymer coatings were
      capable of surviving exposure to high-temperature solvent conditions (200 degrees
      C) with little change in extraction capabilities. This demonstrates that sol-gel
      germania triblock polymer hybrid materials might be suitable for further
      applications in high-temperature HPLC. The reproducibility of the method for
      preparation of the sol-gel germania triblock polymer coatings was also evaluated,
      and the capillary-to-capillary RSD values ranged from 5.3 to 6.5%. The use of
      higher flow rates in extraction was found to significantly reduce the time
      required (from 30-40 to 10-15 min) to reach equilibrium between the sol-gel
      germania triblock polymer coating and the analytes in the sample solution.

PMID- 20691974
TI  - A novel method for analyzing solanesyl esters in tobacco leaves using atmospheric
      pressure chemical ionization/mass spectrometer.
AB  - A direct and simple method for analyzing solanesyl esters found in tobacco leaves
      was developed. Sample preparation was performed by accelerated solvent extractor
      200 (ASE200) using n-hexane followed by evaporating solution in vacuo and
      dissolving residue with acetone. The separation of analytes was conducted through
      high-performance liquid chromatography (HPLC) equipped with an SIL-C18/5C column
      and the non-aqueous reversed phase chromatography (NARP) technique using acetone
      and acetonitrile as the mobile phase with a linear gradient. Atmospheric pressure
      chemical ionization/mass spectrometer (APCI/MS) in positive mode was used to
      detect solanesyl esters in the following conditions: capillary voltage 4000 V,
      corona current 10 microA, drying gas flow 5 mL/min, fragmentor voltage 200 V,
      nebulizer pressure 60 psi, and vaporizer temperature 500 degrees C. Each
      solanesyl ester was identified by the comparison of analyte with synthesized
      solanesyl esters. Quantification was conducted by selected ion monitoring (SIM)
      mode in order to detect the specific product ion (613.6 m/z) fragmented from
      solanesyl ester. The calibration curve was made in the range of 0.1-40 microg/mL
      with a regression coefficient over 0.999 on almost all solanesyl esters. The
      limit of detection (LOD) and limit of quantification (LOQ) ranged from 0.01 to
      0.05 microg/mL and from 0.03 to 0.15 microg/mL, respectively, on the SIM mode of
      MS for quantification. Recovery (%) ranged from about 80 to 120%. The direct
      quantification using the developed method succeeded in showing a different amount
      and composition of solanesyl esters among various tobacco leaves.

PMID- 20691976
TI  - Poly(divinylbenzene-alkyl methacrylate) monolithic stationary phases in capillary
      electrochromatography.
AB  - In this study, a series of poly(divinylbenzene-alkyl methacrylate) monolithic
      stationary phases, which were prepared by single step in situ polymerization of
      divinylbenzene and various alkyl methacrylates (butyl-, octyl-, or lauryl
      methacrylate), were developed as separation columns of benzophenone compounds for
      capillary electrochromatography (CEC). In addition to the presence of plenty of
      benzene moieties, the stationary phases contained long and flexible alkyl groups
      on the surface. With an increase in the molecular length of alkyl methacrylate,
      the polymeric monolith, which had higher hydrophobicity, effectively reduced the
      peak tailing of benzophenones, but a weaker retention was observed. The unusual
      phenomenon was likely due to the pi-pi interaction between the aromatic compound
      and the polymeric material. The usage of longer alkyl methacrylate as reaction
      monomer limited the retention of aromatic compounds on the stationary phase
      surface, thus the pi-pi interaction between them was possibly reduced.
      Consequently, the retention time of aromatic compounds was markedly decreased
      with an increase in carbon length of alkyl methacrylate that was carried on the
      polymeric monolith. Compared to previous reports on polystyrene-based columns in
      which the peak-tailing problem was reduced by decreasing the benzene moieties on
      the stationary phase, this study demonstrated that the undesirable retention
      (peak-tailing) could also be improved by the inclusion of long alkyl methacrylate
      to the polystyrene-based columns.

PMID- 20691977
TI  - Drag force on spheres confined on the center line of rectangular microchannels.
AB  - Via Lattice Boltzmann simulations we show there is a great deal of universality
      in the reduced mobility of spheres moving along the centre line of capillaries or
      rectangular microchannels. The reduced mobility follows a generalization of the
      Haberman-Sayre correlation, which is a function of the degree of confinement, e.
      This quantity e=d(p)/D(e), is defined as the ratio of the particle diameter and
      the length scale D(e), which is a weighted mean of the square root of the cross
      section area D(A), and the hydraulic diameter D(h). The force experienced by
      spheres in pressure driven flow can be described by a generalized Faxen theorem,
      combined with effective medium theory. This force can be decomposed in a drag
      force and a pressure gradient force, both inversely proportional to the reduced
      mobility.

PMID- 20691978
TI  - Liquid withdrawal from capillary tubes: explicit and implicit analytical solution
      for constant and dynamic contact angle.
AB  - In a preceding paper, we derived analytical solutions for the displacement of a
      gas by a liquid in horizontal and inclined capillary tubes where the tube inlet
      is connected to a liquid reservoir of constant pressure. We considered quite
      general models for the dynamic contact angle and were able to derive implicit
      equations for the velocity of the gas-liquid interface. These solutions allowed
      us to identify five different flow scenarios for liquid withdrawal that differed
      in the direction of flow and the sign of the acceleration of the gas-liquid
      interface. In this paper, we consider the special case where the dynamic contact
      angle is determined by a nonequilibrium Young force that depends linearly on the
      capillary number. Thus we can derive explicit and the more traditional implicit
      analytical solutions for both the position and the velocity of the gas-liquid
      interface. We also construct diagrams that allow us to predict which of the five
      flow scenarios will occur depending on the nondimensional parameters that define
      the problem. The diagrams can be combined with diagrams previously obtained for
      infiltration and the entire parameter space subdivided into regions that are
      associated with either liquid withdrawal, liquid infiltration, or metastable and
      stable equilibrium states. Our solutions are also valid within the limit where
      the contact angle is constant.

PMID- 20691979
TI  - The influence of neighborhood density and word frequency on phoneme awareness in
      2nd and 4th grades.
AB  - PURPOSE: The purpose of this study was to test the hypothesis that two lexical
      characteristics - neighborhood density and word frequency - interact to influence
      performance on phoneme awareness tasks. METHODS: Phoneme awareness was examined
      in a large, longitudinal dataset of 2nd and 4th grade children. Using linear
      logistic test model, the relation between words' neighborhood density, word
      frequency, and phoneme awareness performance was examined across grades while co
      varying type and place of deletion. RESULTS: A predicted interaction was
      revealed: words from dense neighborhoods or those with high frequency were more
      likely to yield correct phoneme awareness responses across grades. CONCLUSIONS:
      Findings support an expansion of the lexical restructuring model to include
      interactions between neighborhood density and word frequency to account for
      phoneme awareness. LEARNING OUTCOMES: The reader will be able to (1) describe the
      lexical restructuring model; (2) define neighborhood density; (3) define word
      frequency; (4) identify how these variables interact to impact phoneme awareness
      performance; (5) identify ways in which future clinical practice may be impacted
      by the study's findings.

PMID- 20691980
TI  - Triptolide and TRAIL combination enhances apoptosis in cholangiocarcinoma.
AB  - BACKGROUND: Cholangiocarcinoma originates from bile duct epithelial cells in the
      intrahepatic and extrahepatic biliary system. We recently observed that
      triptolide (a diterpenoid triepoxide) is effective in inducing apoptosis in
      pancreatic tumors. Death receptors 4 and 5 are overexpressed in several cancer
      types, and their activation by tumor-necrosis factor-related apoptosis-inducing
      ligand (TRAIL) induces cell death. The principal objective of this study was to
      determine the effects of combination therapy with TRAIL and triptolide in
      cholangiocarcinoma. MATERIALS AND METHODS: Two cholangiocarcinoma cell lines were
      incubated with various doses of triptolide and TRAIL, alone and in combination;
      cell viability was assessed at 24 and 48 h. Annexin-V staining and caspase-3
      activity were measured after 24 h of triptolide, TRAIL or combination treatment.
      Western blots assessed protein levels of poly(ADP-ribose) polymerase (PARP) and X
      linked inhibitor of apoptosis (XIAP). RESULTS: Combination treatment using TRAIL
      and triptolide decreased cell viability in all cell lines at 48 h, with greater
      cell killing than that which was observed with either drug alone. This decrease
      in viability was associated with increases in annexin-V staining and caspase-3
      activity. Western blot analysis demonstrated increases in PARP cleavage and
      decreases in XIAP expression that were dose-dependent. CONCLUSIONS: TRAIL and
      triptolide in combination decreased cell viability and enhanced apoptosis.
      Furthermore, Western blot analysis suggests that triptolide sensitizes cells to
      TRAIL-induced apoptotic cell death by inhibiting expression of XIAP, a protein
      known to inhibit apoptosis. Our results demonstrate that combination of TRAIL and
      triptolide enhance apoptosis in cholangiocarcinoma cell lines.

PMID- 20691981
TI  - Assessment of surgical and obstetrical care at 10 district hospitals in Ghana
      using on-site interviews.
AB  - BACKGROUND: For most of the population in Africa, district hospitals represent
      the first level of access for emergency and essential surgical services. The
      present study documents the number and availability of surgical and obstetrical
      care providers as well as the types of surgical and obstetrical procedures being
      performed at 10 first-referral district hospitals in Ghana. MATERIALS AND
      METHODS: After institutional review board and governmental approval, a study team
      composed of Ghanaian and American surgeons performed on-site surveys at 10
      district hospitals in 10 different regions of Ghana in August 2009. Face-to-face
      interviews were conducted documenting the numbers and availability of surgical
      and obstetrical personnel as well as gathering data relating to the number and
      types of procedures being performed at the facilities. RESULTS: A total of 68
      surgical and obstetrical providers were interviewed. Surgical and obstetrical
      care providers consisted of Medical Officers (8.5%), nurse anesthetists (6%),
      theatre nurses (33%), midwives (50.7%), and others (4.5%). Major surgical cases
      represented 37% of overall case volumes with cesarean section as the most common
      type of major surgical procedure performed. The most common minor surgical
      procedures performed were suturing of lacerations or episiotomies. CONCLUSIONS:
      The present study demonstrates that there is a substantial shortage of adequately
      trained surgeons who can perform surgical and obstetrical procedures at first
      referral facilities. Addressing human resource needs and further defining
      practice constraints at the district hospital level are important facets of
      future planning and policy implementation.

PMID- 20691982
TI  - Setting the standards: how we can be the arbiters of health care quality?

PMID- 20691983
TI  - Dose variation of hepatocyte growth factor and its effects on an animal model of
      TPN-induced liver injury.
AB  - BACKGROUND: Total parenteral nutrition (TPN) induced liver failure is the leading
      indication for transplantation in children. Our previous research demonstrated
      the benefit of a specific intravenous dose of hepatocyte growth factor (HGF) in
      the amelioration of TPN-induced liver injury. This study was designed to
      ascertain the optimum concentration of HGF in an animal model of TPN-induced
      liver injury. MATERIALS AND METHODS: Twenty adult female Sprague-Dawley rats
      underwent 70% small bowel resection and placement of venous catheters connected
      to subcutaneous osmotic minipumps. Four groups (n=5 each) based on the contents
      of the osmotic pump were utilized as follows: group 1 (control): saline; group 2:
      HGF 75 mcg/kg/d; group 3: HGF 150 mcg/kg/d; and group 4: HGF 250 mcg/kg/d. Each
      rat received 14 d of TPN without enteral nutrition. After sacrifice, the liver
      was harvested. Hepatic inflammation was evaluated using antibodies for TNF-alpha
      and IL-6. Apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP
      nick end labeling (TUNEL) technique. RESULTS: All concentrations induced
      statistically significantly less IL-6 and TNF- alpha expression compared to the
      control animals. Increased efficacy was demonstrated with increasing dose
      concentration up to 150 mcg/kg/d but not 250 mcg/kg/d. Apoptotic activity was
      decreased statistically significantly for all dose concentrations compared with
      the controls, as well as to increases in dose concentration. CONCLUSIONS:
      Increasing concentrations of HGF were directly correlated with increased
      modulation of inflammatory response and apoptotic index in this animal model for
      TPN-induced liver injury, up to 150 mcg/kg/d. Further increases were significant
      with respect to apoptotic index only. Further investigations are warranted to
      determine if HGF may be useful to minimize TPN-induced liver injury in children.

PMID- 20691984
TI  - Uncoupling protein-2 deficient mice are not protected against warm
      ischemia/reperfusion injury of the liver.
AB  - BACKGROUND: Uncoupling protein-2 (UCP2) might play an important role in mediating
      ischemia/reperfusion (I/R) injury due to its function in uncoupling of oxidative
      phosphorylation and in the proton leak-associated increase of reactive oxygen
      species (ROS) production. The aim of this study was to elucidate the role of UCP2
      in hepatic I/R injury. MATERIALS AND METHODS: UCP2 wild type and UCP2 deficient
      mice were subjected to I/R of the left liver lobe. Sham-operated animals without
      I/R served as controls. Intravital fluorescence microscopy was used for assessing
      postischemic microcirculatory dysfunction. Indicators of hepatic inflammatory
      response, oxidative stress, and bioenergetic status as well as histomorphology
      were investigated. RESULTS: Under sham conditions UCP2-/-mice presented slightly
      but not significantly higher levels of hepatic ATP and energy charge than wild
      type mice. In addition, they exhibited higher systemic IL-6 levels and
      intrahepatic leukocyte adherence. After exposure to I/R, the extent of
      reperfusion injury did not differ between UCP2+/+ and UCP2-/-mice, as indicated
      by a comparable loss of sinusoidal perfusion, hepatic ATP, and energy charge
      levels, as well as rise of transaminases and disintegration of liver structures.
      Intrahepatic leukocyte adherence and plasma IL-6 levels of postischemic UCP2-/
      mice still exceeded those of UCP2+/+mice. CONCLUSIONS: UCP2 appears to be of
      minor relevance for the manifestation and extent of postischemic reperfusion
      injury in nondiseased livers with the increased ATP availability being
      counteracted by the higher pro-inflammatory IL-6 levels in UCP2 deficient mice.

PMID- 20691985
TI  - LPS-induced epithelial-mesenchymal transition of intrahepatic biliary epithelial
      cells.
AB  - BACKGROUND: Recent studies have revealed that the epithelial-mesenchymal
      transition (EMT) of bile duct epithelial cells is engaged in hepatic
      fibrogenesis. However, the association between etiological factors of liver
      disease such as virus or bacterial infection and EMT remains to be investigated.
      The present study focuses on the inductive role of endotoxin, the main component
      of the cell wall's ectoblast of gram-negative bacteria, in the EMT of human
      intrahepatic biliary epithelial cells (HIBEpiCs). METHODS: The expressions of E
      cadherin, S100A4, alpha-SMA, TGF-beta1, and Smad2/3 in HIBEpiCs cultured with or
      without lipopolysaccharide LPS, were detected by real-time PCR and Western
      blotting. We blocked the expression of TGF-beta1 using paclitaxel and knocked
      down Smad2/3 by siRNA to explore the role of TGF-beta1/Smad2/3 pathway in the EMT
      of HIBEpiCs. RESULTS: Resting HIBEpiCs showed epithelioid cobblestone morphology,
      and underwent a phenotypic change to produce bipolar cells with a fibroblastic
      morphology when co-cultured with LPS. After LPS stimulation and the up-regulation
      of mRNA and protein expression of TGF-beta1 and Smad2/Smad3, the mRNA and protein
      expression of mesenchymal markers (S100A and alpha-SMA) increased significantly.
      Paclitaxel inhibited the mRNA and protein expression of TGF-beta1 in vitro. Knock
      down of Smad2/3 by siRNA led to up-regulation of epithelial markers E-cadherin
      and down-regulation of S100A and alpha-SMA, indicating a reversal of the EMT.
      CONCLUSIONS: LPS can induce the expression of TGF-beta1 and a subsequent EMT in
      HIBEpiCs, and the inhibition of TGF-beta1 or Smad 2/3 could reverse this EMT,
      suggesting that LPS may play a potential role in the EMT of HIBEpiCs.

PMID- 20691986
TI  - The utility of a tissue slice model system to determine breast cancer infectivity
      by oncolytic adenoviruses.
AB  - BACKGROUND: Due to advances in viral design, oncolytic adenoviruses have emerged
      as a promising approach for treatment of breast cancer. Tumor tissue slices offer
      a stringent model system for preclinical evaluation of adenovirus therapies,
      since the slices retain a morphology and phenotype that more closely resembles
      the in vivo setting than cell line cultures, and this system has been shown to
      have utility in the evaluation of viral infectivity and replication. In this
      study, we evaluated the efficacy of viral infection and replication using a
      tropism-modified oncolytic adenovirus. METHODS: Breast tumor tissue slices were
      infected with a tropism-modified oncolytic adenovirus, and a wild-type adenovirus
      for comparison. Efficiency of infection was evaluated using fluorescent
      microscopy, as the viruses used have been modified to express red fluorescent
      protein. Replication of the viruses was evaluated with quantitative real-time
      polymerase chain reaction (PCR) to assay viral E4 genome copy number, a surrogate
      indicator for the number of virions. The breast tumor tissue slices were
      evaluated for the expression of CD46 expression by immunohistochemistry. RESULTS:
      Infection and replication of our tropism modified oncolytic virus has been
      observed in the breast cancer tissue slice model system and is comparative to
      wild-type virus. A qualitative increase in the number of cells showing red
      fluorescent protein (RFP) expression was observed correlating with increasing
      multiplicity of infection. Higher relative infectivity of the virus was observed
      in tumor tissue compared with normal breast tissue. Replication of the virus was
      demonstrated through increases in E4 copy number at 48 and 72 h after infection
      in human breast tumor slices. CONCLUSIONS: We have shown that a tropism modified
      oncolytic adenovirus can infect and replicate in breast cancer tissue slices,
      which may be an important preclinical indicator for its therapeutic utility.

PMID- 20691987
TI  - Dehydroepiandrosterone during sepsis: does the timing of administration influence
      the effectiveness.
AB  - BACKGROUND: Administration of dehydroepiandrosterone (DHEA) has been demonstrated
      to improve survival and cellular immune functions during systemic inflammation.
      Although there is evidence that the time point of drug application may profoundly
      affect the DHEA-induced effects the impact of this parameter remains to be
      established. METHODS: Male NMRI mice were subjected to sham-operation
      (laparotomy) or sepsis (cecal ligation and puncture). Animals received saline or
      DHEA (20 mg/kg/d) given subcutaneously either 1 h before or 8 h after induction
      of CLP. Termination of animals was performed 48 h after induction of sepsis in
      order to monitor splenocyte proliferation ((3)H-thymidine incorporation assay),
      splenocyte apoptosis (annexin V binding capacity), and cytokine release (IL-1beta
      and IL-6, enzyme-linked immunoassay (ELISA). RESULTS: DHEA administration
      improved the survival rate of septic mice 48 h after induction of CLP independent
      of the time point of application (44% versus 75% pretreatment groups; 47% versus
      78% treatment groups). This effect was paralleled by a restoration of splenocyte
      proliferation, a decreased cellular apoptosis rate of splenocytes, and a
      modulation of pro-inflammatory cytokine release. CONCLUSIONS: Administration of
      DHEA either given before or after the development of clinical apparent septic
      symptoms reliably improves survival and cellular immune functions in a murine
      model of sepsis.

PMID- 20691989
TI  - Bradykinin and the heart: left, right, or both?

PMID- 20691988
TI  - The role of 5-HT3 and 5-HT4 receptors in the adaptive mechanism of colonic
      transit following the parasympathetic denervation in rats.
AB  - BACKGROUND: Clinical studies show that disturbed colonic motility induced by
      extrinsic nerves damage is restored over time. We studied whether 5-HT3 and 5HT4
      receptors are involved in mediating the adaptive mechanisms following
      parasympathetic denervation. METHODS: Parasympathetic denervation of the entire
      colon was achieved by bilateral pelvic nerve transection and truncal vagotomy in
      rats. Colonic transit was measured by calculating the geometric center (GC) of
      51Cr distribution. Expression of 5-HT3 and 5HT4 receptor mRNA was determined by
      real time RT-PCR. RESULTS: Parasympathetic denervation caused a significant delay
      in colonic transit (GC=4.36) at postoperative day (POD) 1, compared with sham
      operation (GC=6.31). Delayed transit was gradually restored by POD 7 (GC=5.99)
      after the denervation. Restored colonic transit was antagonized by the
      administration of 5-HT3 and 5HT4 receptors antagonists at POD 7. 5-HT3 and 5HT4
      receptors mRNA expression were significantly increased in the mucosal/submucosal
      layer at POD 3 or POD 7, whereas no significant difference was observed in the
      longitudinal muscle layers adherent with the myenteric plexus (LMMP).
      CONCLUSIONS: It is suggested that up-regulation of 5-HT3 and 5-HT4 receptors
      expression in the mucosal/submucosal layer is involved to restore the delayed
      transit after the parasympathetic denervation in rats.

PMID- 20691990
TI  - A rabbit model for selective portal vein embolization.
AB  - BACKGROUND: Portal vein embolization (PVE) is a technique to increase future
      remnant liver volume. A standardized animal model, resembling the clinical PVE
      procedure, is needed to clarify some of the unresolved issues surrounding PVE.
      For this purpose we developed a new rabbit model for PVE. MATERIALS AND METHODS:
      Twenty female New Zealand white rabbits were allocated to two protocols, each
      containing two subgroups. Eighty percent of the liver portal venous system was
      embolized with polyvinyl-alcohol particles and coils (protocol 1: 300-500 MUm
      particles and one coil; protocol 2: 90-180 MUm combined 300-500 MUm particles and
      three coils). In all rabbits CT-volumetry, ICG clearance test, blood sampling,
      and portography were performed prior to PVE and at d 7 and 14. Additional blood
      sampling and CT volumetry was done on d 3 and 7. RESULTS: PVE was technically
      feasible in the rabbit. CT-volumetry demonstrated a strong correlation with
      actual liver weight and volume measured at sacrifice. The hypertrophy response
      was highest at d 7 in both protocols, which was consistent with the amount of
      proliferating hepatocytes. Protocol 2 showed less revascularization of the portal
      venous system and demonstrated the highest hypertrophy response. Comparable to
      the clinical situation, only a small, transient increase in transaminases was
      observed. There were no changes in liver function parameters after PVE.
      Histopathologic findings in the rabbit livers were comparable to those found in
      human livers. CONCLUSIONS: We successfully devised a rabbit model for PVE, which
      resembles the human clinical situation.

PMID- 20691991
TI  - Kidney transplantation in mice using left and right kidney grafts.
AB  - BACKGROUND: Mouse kidney transplantation is a powerful tool for scientific
      research. The conventional method uses only the left donor kidney for grafting
      because of shorter renal vessels on the right side. MATERIALS AND METHODS: We
      developed a new technique of harvesting both left and right kidneys from one
      donor mouse, and separately transplanted them into two recipients. Forty-six
      kidney grafts (23 left, 23 right kidneys) were transplanted to 46 recipient mice.
      Life-supporting kidney transplantation (in which both recipient kidneys were
      removed) was performed in 12 recipients (six of each group). RESULTS: Cold
      ischemia times were considerably longer for the second kidney graft (2.5-3 versus
      1 h), which resulted in reduced graft function at early time points. However, the
      14 d survival rate was comparable with 80% for right and 70% for left kidney
      grafts. Recipient animals were sacrificed between 1 and 6 wk after
      transplantation. Histologic examination of surviving grafts showed intact renal
      parenchyma, whereas total necrosis was usually seen in failed grafts. The causes
      of graft failure were thrombosis of the renal artery, narrow outflow of the renal
      vein, and fistula of the ureter. In a subgroup of animals, specific staining for
      apoptosis was performed. A tendency for a higher rate of apoptosis was seen at 1
      wk compared with 6 wk post-transplant, but no correlation with cold ischemia time
      was found. CONCLUSION: We report a new microsurgical technique of mouse kidney
      transplantation using both right and left donor kidneys as grafts for two
      recipient mice. Right kidney grafts showed equal survival compared with left
      kidney grafts. Thus, this technique reduces overall operating time and costs for
      microsurgery experiments.

PMID- 20691992
TI  - Enhanced aortic nerve growth factor expression and nerve sprouting in rats
      following gastric perforation.
AB  - BACKGROUND: Nerve growth factor (NGF) up-regulation during inflammation has been
      demonstrated to occur in several different tissues. Herein, the expression of
      aortic nerve growth factor and its association with nerve sprouting in a rodent
      model of self-limited peritonitis were investigated. MATERIALS AND METHODS: Male
      Wistar rats were randomized into one of three groups: gastric perforation (GP),
      sham group, and GP group treated with methylprednisolone (GP-M). Aortic
      expression of NGF and growth associated protein 43 (GAP43) were evaluated at
      several different time points (range, 6 h to 2 wk) after GP or sham. RESULTS:
      Compared with the sham group, expression of NGF was significantly elevated during
      the inflammatory period (the first week post-GP) in GP rats. The GP group also
      had enhanced nerve sprouting, which persisted after the peritonitis recovered.
      Methylprednisolone abrogated NGF up-regulation and nerve sprouting induced by GP.
      CONCLUSIONS: GP resulted in up-regulation of aortic NGF that coincided with
      aortic nerve sprouting. Methylprednisolone effectively blocked GP-induced NGF up
      regulation. Further studies are necessary to decipher the causality of these
      observed changes.

PMID- 20691993
TI  - Protective effects of dexpanthenol and y-27632 on stricture formation in a rat
      model of caustic esophageal injury.
AB  - BACKGROUND: This experimental study was conducted to investigate the effect of
      dexpanthenol (converted in the body to pantothenic acid) and Y-27632 (a selective
      Rho-kinase inhibitor) on stricture formation after caustic (alkaline) esophageal
      injury in rats. MATERIALS AND METHODS: Sixty male Wistar albino rats were
      randomly allocated into six groups. In group 1 (sham) the distal esophagus was
      isolated and cannulated but no caustic injury was induced. In all remaining
      groups, a caustic esophageal burn was induced with 50% sodium hydroxide solution
      for 90 s and drug treatment was given by daily intraperitoneal injection,
      beginning 24 h after injury and continuing for 21 d. In group 2 (controls),
      animals were treated with 0.9% saline; in groups 3 and 4, with 50 and 500 mg/kg/d
      of dexpanthenol, respectively; and in groups 5 and 6, with 0.3 and 3 mg/kg/d of Y
      27632, respectively. Rats were sacrificed 22 d after caustic injury and the
      distal esophagus was isolated for histopathology and biochemical investigation.
      RESULTS: Stenosis index and collagen deposition scores were significantly lower
      in both the dexpanthenol and Y-27632 treated groups (P<0.05). Dexpanthenol and Y
      27632 treatment markedly depressed esophageal tissue malondialdehyde and
      hydroxyproline levels. CONCLUSION: In this experimental model of caustic
      esophageal stricture, dexpanthenol and Y-27632 significantly attenuated
      esophageal stricture formation. These findings indicate that inhibition of Rho
      kinase or dexpanthenol administration may offer novel therapeutic approaches in
      the treatment of caustic esophageal injury.

PMID- 20691994
TI  - Acute appendicitis in latino children: do health disparities exist?
AB  - BACKGROUND: Significant racial and socioeconomic disparities have been found in
      the diagnosis and treatment of acute appendicitis in children. There has been
      little focus on the outcomes of Latino children with appendicitis. This study
      evaluates whether ethnicity or insurance status are associated with differences
      in presentation and outcomes of children with acute appendicitis. MATERIALS AND
      METHODS: A retrospective analysis was performed for all children between the ages
      of 2 and 18 y with acute appendicitis between July 1, 2005 and December 31, 2008
      at the only teaching hospital in the region. chi(2) and regression analyses were
      used to evaluate the impact of ethnicity and insurance status on perforation
      rates and outcomes. RESULTS: A total of 410 children with acute appendicitis were
      identified, of whom 259 (63.2%) were Latino. Latino children were on public
      insurance in greater proportion (34.8% versus 19.9%) compared with non-Latino
      children (P = 0.001). The perforation rate for the entire sample was 29.6%. There
      were no significant differences in perforation rates with respect to ethnicity,
      insurance status (private, public, none), or age. Once within the medical system,
      there were no significant differences in radiologic studies performed, types of
      operations received, length of stay, or number of complications between ethnic
      groups. CONCLUSIONS: There have been multiple reports showing disparities in the
      rates of perforated appendicitis in children. At our institution, we observed no
      differences in the presentation and care of children with acute appendicitis with
      respect to ethnicity and insurance status.

PMID- 20691995
TI  - Cyanoacrylate surgical glue as an alternative to suture threads for mesh fixation
      in hernia repair.
AB  - BACKGROUND: In recent years, the use of synthetic glues has become an established
      practice in several areas of surgical treatment. For example, they are used in
      open and laparoscopic surgery and in digestive tract endoscopy, interventional
      radiology, and vascular neuroradiology. The experiments in this study were aimed
      at elucidating that suture-based permanent mesh fixation can be replaced by
      fixation with N-butyl 2-cyanoacrylate glue (Glubran2) for surgical repair of
      abdominal wall hernias. MATERIALS AND METHODS: In 25 Wistar rats, two hernia
      defects (1.5 cm in diameter) per animal were created bilaterally in the midline
      of the abdominal wall. The peritoneum was spared. The lesions were left untreated
      for 10 d to achieve a chronic condition. Then the defects were covered with
      TiMESH extralight (2 * 2 cm) and fixed by 30 MUL of Glubran2 or traditional
      suture. The time points of sacrifice were 17 and 28 d, 3, 4, and 5 mo. At
      autopsy, histology and immunohistochemistry were performed to evaluate the
      inflammatory response and the presence of apoptotic cells respectively. RESULTS:
      Mesh fixation was excellent in all samples at each time point. At application
      sites, the inflammatory reaction was mild with a small number of macrophages and
      vascularized connective tissue presence around glue and mesh threads. Glue
      residues were observed in histologic sections at each time point. No presence of
      apoptotic cells was found. CONCLUSIONS: This study demonstrated that Glubran2 can
      effectively replace traditional suture in mesh fixation without affecting tissue
      healing and determining a physiological inflammatory reaction at the abdominal
      wall site.

PMID- 20691997
TI  - Multipurpose simulator for technical skill development in thoracic surgery.
AB  - BACKGROUND: Our appreciation for the increased role of simulation in surgical
      education has led us to develop a simulator for effective training of fundamental
      invasive thoracic skills. MATERIALS AND METHODS: Study subjects were fourth year
      medical students (MS-4, n = 6) rotating on a surgery clerkship, and surgical
      interns (PGY-1, n = 6). All subjects completed demographic surveys and rated
      their comfort level performing the thoracic skills. A computerized instructional
      module was given to all participants. Additionally, interns attended a boot camp
      with didactics, live demonstrations, and supervised practice sessions. Subjects
      were asked to perform a thoracentesis and insert a chest tube on the models,
      repetitively, during three sessions, and their skills were rated. Participants
      were asked to rate their comfort levels performing the procedure before and after
      the sessions. RESULTS: Interns reported a greater exposure to surgery (9.7 +/-
      3.2 wk versus 6 +/- 1.8 wk; P = 0.03). Although interns were initially faster,
      operative times were comparable by the third session. Initially, technical skill
      ratings for thoracentesis were significantly lower in the MS-4 group (P < 0.03).
      The scores significantly increased by the final simulation (P <= 0.04), and were
      similar to the PGY-1 skill ratings. Significant improvement with chest tube
      placement each week (P <= 0.05), resulted in scores comparable to the intern
      group as well. Both groups reported higher comfort levels after the simulation
      sessions. CONCLUSIONS: Our simulation trainers were effective educational tools
      for fundamental thoracic procedures. Our study demonstrates improved technical
      skill and higher comfort levels with the simulated procedures.

PMID- 20691996
TI  - Overexpression of COX-2 in celecoxib-resistant breast cancer cell lines.
AB  - BACKGROUND: Cyclooxygenase-2 (COX-2) plays a key role in breast cancer
      progression and metastasis. Effective therapeutic targeting of COX-2 would
      require the knowledge of whether a tumor is addicted to COX-2, and if we can
      counter the potential resistance to anti-COX-2 therapy. Herein we tested the
      hypothesis that celecoxib-resistance involves selection of cancer cells that
      overexpress COX-2. MATERIALS AND METHODS: We selected celecoxib-resistant (CER)
      variants from two metastatic cell lines, SUM149 inflammatory breast cancer (IBC)
      cell line and MDA-MB-231-BSC60 cell line, by culturing them in the presence of
      celecoxib. We measured the relative levels of COX-2 protein and its network
      components Bcl-2, Bcl-xL, and Bax in the parental cell lines and their CER
      variants by Western blotting. To determine whether celecoxib resistance would
      increase tumorigenicity, we performed an in vitro clonogenicity assay. We
      determined the statistical significance of differences between the groups using
      the two-sample t-test. RESULTS: Both the celecoxib-resistant cell lines SUM149
      CER and BSC60-CER produced significantly higher levels of COX-2 protein than
      their parental counterparts (P < 0.05). The CER variants produced a reduced level
      of pro-apoptosis protein Bax (both cell lines) and increased levels of anti
      apoptosis proteins Bcl-2 (BSC60) or Bcl-xL (SUM149). Importantly, the CER
      variants had significantly higher clonogenicity than their parental cell lines (P
      < 0.05). The siRNA-mediated COX-2 knockdown in SUM149-CER cell line resulted in a
      significant decrease in clonogenicity and in Bcl-xL and Bcl-2 protein levels,
      thus supporting our hypothesis. CONCLUSION: Celecoxib-resistant variant cells
      present in breast cancer cell lines overexpress COX-2, which is robustly linked
      with survival pathways and clonogenicity. Since COX-2 is important in the variant
      cancer cells of aggressive nature, it represents a good therapeutic target.

PMID- 20691998
TI  - Serum proteomic analysis from bacteremic and leucopenic rabbits.
AB  - BACKGROUND: Bacteremia causes mild to life-threatening illnesses as a consequence
      of inflammatory pathway activation, and leucopenia can increase mortality rates
      and treatment costs. The identification of novel biomarkers for leucopenia in the
      context of bacteremia would facilitate early detection and provide insights into
      the identification of novel therapeutic targets. METHODS: Rabbits were infected
      with Klebsiella pneumoniae to induce bacteremia with leucopenia, and sera from
      infected and noninfected rabbits was subjected to proteomic analysis using two
      dimensional gel electrophoresis (2-DE) and mass spectrometry (MS) to compare
      serum protein profiles. RESULTS: Five differentially-expressed protein spots were
      identified in bacteremic rabbits with leucopenia compared to protein expression
      profiles prior to infection. The proteins were identified as desmin, cystic
      fibrosis transmembrane conductance regulator (CFTR), interleukin (IL) 4, and the
      interleukin 6 precursor. The increased levels of desmin and CFTR in serum were
      further confirmed by Western blot analysis. CONCLUSIONS: These results indicated
      that desmin, CFTR, IL-4, and the IL-6 precursor may be potential molecular
      biomarkers for leucopenia occurring with bacteremia.

PMID- 20691999
TI  - Predictive value of preoperative tissue Doppler echocardiographic analysis for
      postoperative atrial fibrillation after pulmonary resection for lung cancer.
AB  - OBJECTIVE: The objective of the present study was to evaluate the utility of
      tissue Doppler imaging for predicting the development of postoperative atrial
      fibrillation. METHODS: In this prospective observational study, we evaluated 126
      patients with lung cancer who underwent a lobectomy during the 18-month period
      from August 2007 to January 2009. Preoperative evaluations for all patients
      included tissue Doppler imaging in addition to conventional echocardiographic
      analysis. The study end point was the development of postoperative atrial
      fibrillation. RESULTS: Postoperative atrial fibrillation was identified in 29
      (23%) patients, in whom significantly higher early transmitral velocity/tissue
      Doppler mitral annular early diastolic velocity values were noted compared with
      those seen in patients without atrial fibrillation (9.76 +/- 2.3 vs 7.14 +/- 1.7,
      P < .0001). The area under the receiver operating characteristic curve for early
      transmitral velocity/tissue Doppler mitral annular early diastolic velocity to
      predict postoperative atrial fibrillation after pulmonary resection for lung
      cancer was 0.83 (95% confidence interval, 0.74-0.92; P < .001). An early
      transmitral velocity/tissue Doppler mitral annular early diastolic velocity value
      of greater than 8 had a sensitivity of 90% and a specificity of 73% for
      predicting postoperative atrial fibrillation. CONCLUSIONS: Postoperative atrial
      fibrillation after pulmonary resection might be associated with left ventricular
      diastolic dysfunction before surgical intervention revealed by using tissue
      Doppler imaging. Additional studies to establish the significance of tissue
      Doppler imaging as a tool to predict postoperative atrial fibrillation could
      contribute to improvements in lung cancer treatments.

PMID- 20692000
TI  - A simplified technique of full-thickness transabdominal laparoscopic repair of
      Morgagni hernia.

PMID- 20692001
TI  - The use of ventricular assist devices in pediatric patients with univentricular
      hearts.

PMID- 20692002
TI  - Thyroid storm after coronary artery bypass grafting.

PMID- 20692003
TI  - Risk model of in-hospital mortality after pulmonary resection for cancer: a
      national database of the French Society of Thoracic and Cardiovascular Surgery
      (Epithor).
AB  - OBJECTIVES: The estimation of risk-adjusted in-hospital mortality is essential to
      allow each thoracic surgery team to be compared with national benchmarks. The
      objective of this study is to develop and validate a risk model of mortality
      after pulmonary resection. METHODS: A total of 18,049 lung resections for non
      small cell lung cancer were entered into the French national database Epithor.
      The primary outcome was in-hospital mortality. Two independent analyses were
      performed with comorbidity variables. The first analysis included variables as
      independent predictive binary comorbidities (model 1). The second analysis
      included the number of comorbidities per patient (model 2). RESULTS: In model 1
      predictors for mortality were age, sex, American Society of Anesthesiologists
      score, performance status, forced expiratory volume (as a percentage), body mass
      index (in kilograms per meter squared), side, type of lung resection,extended
      resection, stage, chronic bronchitis, cardiac arrhythmia, coronary artery
      disease, congestive heart failure, alcoholism, history of malignant disease, and
      prior thoracic surgery. In model 2 predictors were age, sex, American Society of
      Anesthesiologists score, performance status, forced expiratory volume, body mass
      index, side, type of lung resection, extended resection, stage, and number of
      comorbidities per patient. Models 1 and 2 were well calibrated, with a slope
      correction factor of 0.96 and of 0.972, respectively. The area under the receiver
      operating characteristic curve was 0.784 (95% confidence interval, 0.76-0.8) in
      model 1 and 0.78 (95% confidence interval, 0.76-0.797) in model 2. CONCLUSIONS:
      Our preference is for the well-calibrated model 2 because it is easier to use in
      practice to estimate the adjusted postoperative mortality of lung resections for
      cancer.

PMID- 20692004
TI  - Validation of an ELISA method for the serological diagnosis of canine brucellosis
      due to Brucella canis.
AB  - In the present study, the validation of an enzyme-linked immunosorbent assay
      (ELISA) for serodiagnosis of canine brucellosis is described. Two different
      antigenic extracts, obtained by heat or ultrasonic homogenization of microbial
      antigens from a wild isolate of Brucella canis bacteria, were compared by ELISA
      and Western blot (WB). A total of 145 canine sera were used to define
      sensitivity, specificity and accuracy of the ELISA as follows: (1) sera from 34
      animals with natural B. canis infection, confirmed by blood culture and PCR, as
      well as 51 sera samples from healthy dogs with negative results by the agar-gel
      immunodiffusion (AGID) test for canine brucellosis, were used as the control
      panel for B. canis infection; and (2) to scrutinize the possibility of cross
      reactions with other common dog infections in the same geographical area in
      Brazil, 60 sera samples from dogs harboring known infections by Leptospira sp.,
      Ehrlichia canis, canine distemper virus (CDV), Neospora caninum, Babesia canis
      and Leishmania chagasi (10 in each group) were included in the study. The ELISA
      using heat soluble bacterial extract (HE-antigen) as antigen showed the best
      values of sensitivity (91.18%), specificity (100%) and accuracy (96.47%). In the
      WB analyses, the HE-antigen showed no cross-reactivity with sera from dogs with
      different infections, while the B. canis sonicate had various protein bands
      identified by those sera. The performance of the ELISA standardized with the heat
      soluble B. canis antigen indicates that this assay can be used as a reliable and
      practical method to confirm infection by this microorganism, as well as a tool
      for seroepidemiological studies.

PMID- 20692005
TI  - Detection of cyprinid herpesvirus-3 DNA in lake plankton.
AB  - The disease caused by cyprinid herpesvirus-3 (CyHV-3) severely impacts the
      natural freshwater ecosystem and damages carp and koi farming, however, the
      pathway of CyHV-3 transmission remains unclear. It is possible that the virus
      adheres to plankton, which then facilitate viral movement and transmission, and
      therefore, it is hypothesised that plankton are involved in the disease dynamics.
      In this study, plankton were collected at eight sites in the Iba-naiko lagoon; we
      detected and quantified CyHV-3 DNA from plankton samples. The results of the
      correlation analysis showed a significant positive correlation between CyHV-3
      copies and the number of Rotifera, suggesting that CyHV-3 binds to and/or is
      concentrated by Rotifera. Our results suggest that plankton affect viral ecology
      in the natural environment.

PMID- 20692006
TI  - Dynamics of sulphur compounds in horizontal sub-surface flow laboratory-scale
      constructed wetlands treating artificial sewage.
AB  - The knowledge regarding the dynamics of sulphur compounds inside constructed
      wetlands is still insufficient. Experiments in planted (Juncus effusus) and
      unplanted horizontal sub-surface-flow laboratory-scale constructed wetlands fed
      with artificial wastewater were carried out to evaluate the sulphate reduction,
      the composition and dynamics of generated sulphur compounds, as well as the
      influence of carbon load and plants on processes of sulphur transformation. In
      planted and unplanted wetlands, the addition of organic carbon (TOC of about 120
      mg L(-1)) immediately affected the transformation of up to 90% of the incoming
      sulphate (150 mg L(-1)), directing it mainly towards elemental sulphur (30%) and
      sulphide (8%). During this experimental period, nearly 52% of the transformed
      sulphate-sulphur was calculated to be immobilized inside the planted wetland and
      66% inside the unplanted one. In subsequent experiments, the deficiency of
      organic carbon inside the planted wetlands favoured the decrease of elemental
      sulphur in the pore water coupled to retransformation of depot-sulphur to
      dissolved sulphate. Nearly 90% of the deposited and reduced sulphur was found to
      be reoxidized. In principle, the results indicate a substantial improvement of
      this reoxidation of sulphur by oxygen released by the helophytes. Surplus of
      organic carbon promotes the ongoing sulphate reduction and the stability of
      deposed and dissolved reduced sulphur compounds. In contrast, inside the
      unplanted control wetland, a relative stability of the formed sulphur depots and
      the generated amount of dissolved sulphur compounds including elemental sulphur
      could be observed independently of the different loading conditions.

PMID- 20692007
TI  - Methanogenic community shift in anaerobic batch digesters treating swine
      wastewater.
AB  - Qualitative and quantitative molecular analysis techniques were used to determine
      associations between differences in methanogenic microbial communities and the
      efficiency of batch anaerobic digesters. Two bioreactors were initially seeded
      with anaerobic sludge originating from a local municipal wastewater treatment
      plant and then supplemented with swine wastewater. Differences were observed in
      the total amount of methane produced in the two bioreactors (7.9L/L, and 4.5L/L,
      respectively). To explain these differences, efforts were taken to characterize
      the microbial populations present using a PCR-based DGGE analysis with
      methanogenic primer and probe sets. The groups Methanomicrobiales (MMB),
      Methanobacteriales (MBT), and Methanosarcinales (MSL) were detected, but
      Methanococcales (MCC) was not detected. Following this qualitative assay, real
      time PCR was used to investigate quantitative differences in the populations of
      these methanogenic orders. MMB was found to be the dominant order present and its
      abundance patterns were different in the two digesters. The population profiles
      of the other methanogenic groups also differed. Through redundancy analysis,
      correlations between the concentrations of the different microbes and chemical
      properties such as volatile fatty acids were calculated. Correlations between MBT
      and MSL populations and chemical properties were found to be consistent in both
      digesters, however, differences were observed in the correlations between MMB and
      propionate. These results suggest that interactions between populations of MMB
      and other methanogens affected the final methane yield, despite MMB remaining the
      dominant group overall. The exact details of why changes in the MMB community
      caused different profiles of methane production could not be ascertained.
      However, this research provides evidence that microbial behavior is important for
      regulating the performance of anaerobic processes.

PMID- 20692008
TI  - Automatic biodetector of water toxicity (ABTOW) as a tool for examination of
      phenol and cyanide contaminated water.
AB  - We describe an automatic biodetector for continuous monitoring of water toxicity
      (ABTOW). Construction of the ABTOW is based on natural ability of the biofilm
      formation to immobilize consortia of nitrifying bacteria (the sensing element) on
      the open cellular polyurethane foam as the support. Change of rates of oxygen
      consumption is used as an indicator of biocatalytic activity (nitrification) of
      the bacteria in response to xenobiotics. Owing to this design the ABTOW features
      stability long-term use, is inexpensive and simple in operation. The dynamics of
      ABTOW response is studied in details for phenol and cyanide as model toxins.
      These data indicate that the sensitivity was 3.5 MUM for phenol and 0.19 MUM for
      cyanide, respectively. The magnitudes of toxic effect were proportional to
      concentration whereas kinetics of the response is an indicator for the mechanism
      of toxicity. Similar methodology is applied to quantify toxicity of a range of
      heavy metals, herbicides and oxidative chain inhibitors. One may conclude that
      the presented biodetector provides a good sensitivity for continuous on-line
      monitoring of toxicity in water.

PMID- 20692009
TI  - Degradation of thiacloprid in aqueous solution by UV and UV/H2O2 treatments.
AB  - Although some studies concerning flash photolysis and photocatalytic ozonation of
      thiacloprid have already been published, no complete investigation and
      explanation of the effects of thiacloprid photodegradation under the conditions
      of UV and UV/H(2)O(2) (high-pressure mercury lamp and H(2)O(2)) have been
      reported yet. The photochemical degradation of thiacloprid (0.32 mM) was studied
      under a variety of solution conditions, by varying the initial concentrations of
      H(2)O(2) from 0 to 162 mM and the pH from 2.8 to 9. In the UV/H(2)O(2) system,
      thiacloprid reacted rapidly, the maximum first-order rate constant (2.7 x 10(
      2)min(-1), r=0.9996) being observed at the H(2)O(2)/thiacloprid molar ratio of
      220 and pH 2.8. Under these conditions, 97% of the thiacloprid was removed in
      about 120 min. The thiacloprid degradation is accompanied by the formation of a
      number of ionic byproducts (Cl(-), acetate, formate, SO(4)(2-), and NH(4)(+)) and
      organic intermediates, so that after 35 h of irradiation, 17% of organic carbon
      remained non-degraded. The application of UV radiation, or H(2)O(2) alone,
      yielded no significant thiacloprid degradation. The study of the rate of removal
      of thiacloprid from natural water showed that it is dominantly influenced by the
      presence of HCO(3)(-).

PMID- 20692010
TI  - First report on interspecies quantitative correlation of ecotoxicity of
      pharmaceuticals.
AB  - Pharmaceuticals being extensively and progressively used in human and veterinary
      medicine are emerging as significant environmental contaminants. Pharmaceuticals
      are designed to have a specific mode of action and many of them are persistent in
      the body. These features among others make pharmaceuticals to be evaluated for
      potential effects on aquatic flora and fauna. Low levels of pharmaceuticals have
      been detected in many countries in sewage treatment plant effluents, surface
      waters, groundwater and drinking waters. In contrast, there is a general scarcity
      of publicly available ecotoxicological data concerning pharmaceuticals.
      Interspecies toxicity correlations provide a tool for estimating contaminant
      sensitivity with known levels of uncertainty for a diversity of wildlife species.
      In this context, we have developed interspecies toxicity correlation between
      Daphnia magna (zooplankton) and fish (species according to OECD guidelines)
      assessing the ecotoxicological hazard potential of diverse 77 pharmaceuticals.
      The developed models are validated and consensus models are presented to predict
      toxicity of the individual compounds for any one species when the data for the
      other species are available. Informative illustrations of the contributing
      structural fragments which are responsible for the greater toxicity of the
      diverse pharmaceuticals are identified by the developed models. Developed models
      are also used to predict fish toxicities of 59 pharmaceuticals (for which Daphnia
      toxicities are present) and Daphnia toxicities of 30 pharmaceuticals (for which
      fish toxicities are present). This study will allow a better and comprehensive
      risk assessment of pharmaceuticals for which toxicity data is missing for a
      particular endpoint.

PMID- 20692011
TI  - Perchlorate in dairy milk and milk-based powdered infant formula in South Korea.
AB  - Perchlorate has been detected in dairy milk and milk-based powdered infant
      formula samples from many different provinces of South Korea. A total of 37 dairy
      milk samples from 12 different brands and 26 milk-based powdered infant formula
      samples from four different brands were tested for the presence of perchlorate.
      These brands and their products, which are analyzed in this study, cover over 95%
      of the dairy milk and milk-based powdered infant formula market share in South
      Korea, which has a population of approximately 50 million inhabitants.
      Perchlorate was explicitly detected by ion chromatography tandem mass
      spectrometry; the limit of quantification (LOQ) for dairy milk and milk-based
      powdered infant formula was 0.12 MUg L(-1) and 1.0 MUg kg(-1), respectively. The
      perchlorate concentration in all the samples was above the LOQ. The perchlorate
      detection data is given as follows: 1.99-6.41 MUg L(-1) (n = 37, mean
      concentration = 4.59 +/- 0.17 MUg L(-1)) for dairy milk and 1.49-33.3 MUg kg(-1)
      (n = 26, mean concentration = 7.83 +/- 0.22 MUg kg(-1)) for milk-based infant
      formula. This study provides increasing evidence that perchlorate commonly occurs
      in dairy products, presumably as the result of perchlorate intake by dairy cattle
      from water and feed.

PMID- 20692012
TI  - Nonideal transport of contaminants in heterogeneous porous media: 8.
      Characterizing and modeling asymptotic contaminant-elution tailing for several
      soils and aquifer sediments.
AB  - Miscible-displacement experiments were conducted to characterize long-term, low
      concentration elution tailing associated with sorption/desorption processes. A
      variety of soils and aquifer sediments, representing a range of particle-size
      distributions and organic-carbon contents, were employed, and trichloroethene
      (TCE) was used as the model organic compound. Trichloroethene transport exhibited
      extensive elution tailing for all media, with several hundred to several thousand
      pore volumes of water flushing required to reach the detection limit. The elution
      tailing was more extensive for the media with higher organic-carbon contents and
      associated retardation factors. However, when normalized by retardation, the
      extent of tailing did not correlate directly to organic-carbon content. These
      latter results suggest that differences in the geochemical nature of organic
      carbon (e.g., composition, structure) among the various media influenced observed
      behavior. A mathematical model incorporating nonlinear, rate-limited
      sorption/desorption described by a continuous-distribution function was used to
      successfully simulate trichloroethene transport, including the extensive elution
      tailing.

PMID- 20692013
TI  - Application of advanced characterization techniques to assess DOM treatability of
      micro-polluted and un-polluted drinking source waters in China.
AB  - China has a very complex water supply system which relies on many rivers and
      lakes. As the population and economic development increases, water quality is
      greatly impacted by anthropogenic processes. This seriously affects the character
      of the dissolved organic matter (DOM) and imposes operational challenges to the
      water treatment facilities in terms of process optimization. The aim of this
      investigation was to compare selected drinking water sources (raw) with different
      DOM character, and the respective treated waters after coagulation, using simple
      organic characterization techniques to obtain a better understanding of the
      impact of source water quality on water treatment. Results from the analyses of
      selected water samples showed that the dissolved organic carbon (DOC) of polluted
      waters is generally higher than that of un-polluted waters, but the specific UV
      absorbance value has the opposite trend. After resolving the high performance
      size exclusion chromatography (HPSEC) peak components of source waters using peak
      fitting, the twelve waters studied can be divided into two main groups (micro
      polluted and un-polluted) by using cluster analysis. The DOM removal efficiency
      (treatability) of these waters has been compared using four coagulants. For water
      sources allocated to the un-polluted group, traditional coagulants
      (Al(2)(SO(4))(3) and FeCl(3)) achieved better removal. High performance poly
      aluminum chloride, a new type of composite coagulant, performed very well and
      more efficiently for polluted waters. After peak fitting the HPSEC chromatogram
      of each of the treated waters, average removal efficiency of the profiles can be
      calculated and these correspond well with DOC and UV removal. This provides a
      convenient tool to assess coagulation removal and coagulant selection.

PMID- 20692014
TI  - Biotransformation of benzothiazole derivatives by the Pseudomonas putida strain
      HKT554.
AB  - We examined the biotransformation of benzothiazole derivatives (BTHs) by an
      axenic microbial culture. A Gram-negative bacterium, tentatively named as strain
      HKT554 and identified as Pseudomonas putida, was able to transform not only
      benzothiazole and 2-mercaptobenzothiazole but also 2-methylthiobenzothiazole,
      which was previously reported as the dead-end product of wastewater treatment.
      GC/MS analysis of the solid-phase extract of the culture broth showed the
      formation of 2-(3H)-benzothiazolone/2-hydroxybenzothiazole from benzothiazole. By
      transposon mutagenesis, a mutant library containing ca. 5000 insertion mutants
      was constructed from the P. putida strain HKT554. Analysis of the disrupted gene
      from one of the mutants showing BTHs transformation deficiency revealed that the
      knocked-out gene was naphthalene dioxygenase. To our knowledge, this is the first
      report on the biotransformation of BTHs by Gram-negative bacteria.

PMID- 20692015
TI  - Occurrence and fate of oseltamivir carboxylate (Tamiflu) and amantadine in sewage
      treatment plants.
AB  - We investigated the occurrence and fate of the two antiviral drugs oseltamivir
      carboxylate (OC)-the active metabolite of Tamiflu-and amantadine (AMT) at three
      sewage treatment plants (STPs) during the 2008-2009 and 2009-2010 influenza
      seasons in Japan. Both compounds were detected in all samples analyzed. The
      concentrations in raw influents at the STPs ranged from 140 to 460 ng L(-1) OC
      and from 184 to 538 ng L(-1) AMT. Primary treatment gave no substantial removal
      of the drugs (OC, 2-9%; AMT, 7-17%). Biological nutrient-removal-based secondary
      treatment (anoxic-oxic-anoxic-oxic and anaerobic-anoxic-oxic) removed 20-37% of
      OC, whereas extended-aeration-based conventional activated sludge treatment
      removed <20%. STPs using primary plus biological secondary treatment removed <50%
      of the drugs. The incorporation of tertiary treatment by ozonation removed >90%.
      Ozonation after secondary treatment in STPs will be necessary during an influenza
      pandemic to reduce the risks associated with the widespread use of antiviral
      drugs.

PMID- 20692016
TI  - Sensitivity of blanket peat vegetation and hydrochemistry to local disturbances.
AB  - At the ecosystem scale, peatlands can be extremely resilient to perturbations.
      Yet, they are very sensitive to local disturbances, especially mechanical
      perturbations (e.g. trampling). The effects of these disturbances on vegetation,
      and potential effects on hydrochemical conditions along the peat surface,
      however, are largely unknown. We used three research tracks (paths researchers
      use to access their study sites) differing in time of abandonment to investigate
      the impact of local disturbance (trampling) on the vegetation and its short-term
      (< or = 2 year) recovery in a flagship research blanket peatland. Additionally,
      we examined the effects of local disturbance on fluvial runoff events and the
      concentrations of dissolved organic carbon (DOC) and particulate organic carbon
      (POC) in runoff water. Local disturbance heavily impacted peat vegetation,
      resulting in large areas of scarred and churned peat. Recovery of vascular plants
      along abandoned tracks was slow, but a functional Sphagnum layer re-established
      after just one year. The absence of vegetation elicited an increase in the number
      of runoff events along the tracks, by which POC runoff from the tracks increased.
      POC concentrations were highest in the surface water from the recently abandoned
      track, while they were low in the runoff water from the track abandoned longest
      and the undisturbed control track. We attribute this to the relatively fast
      recovery of the Sphagnum vegetation. DOC concentrations did not differ
      significantly either spatially or temporally in surface runoff or soil solution
      waters. While at an ecosystem scale local disturbances may be negligible in terms
      of carbon loss, our data points to the need for further research on the potential
      long-term effects of local disturbance on the vegetation, and significant effects
      on local scale carbon fluxes. Moreover, the effects of disturbances could be long
      lasting and their role on ecosystem processes should not be underestimated.

PMID- 20692017
TI  - Removal and accumulation of Cu, Ni and Zn in horizontal subsurface flow
      constructed wetlands: contribution of vegetation and filling medium.
AB  - This study investigated the accumulation and removal of Cu, Ni and Zn in two
      horizontal subsurface flow constructed wetlands for domestic wastewater
      treatment, which differ by shape, presence of macrophytes and water depth.
      Between March and December 2007, the three metals were measured in the influent
      and effluents of the two systems. Average percentage removal rates were extremely
      low for Cu (3% and 9% in the two beds) and higher for Zn and Ni (between 25 and
      35%). Under higher Zn influent concentrations, it was found to be between 78-87%,
      which is in agreement with other literature data. During the peak standing crop
      season (August), biomasses of the different parts of Phragmites australis (stems,
      leaves and flowers, roots and rhizomes) were analysed in terms of weight and
      heavy metal concentration in order to assess heavy metal distribution among the
      tissues. It was found that the plants contribute to total heavy metal removal to
      a lesser extent than the filling medium. Aboveground tissues remove 34% of Cu,
      1.8% of Ni and 6.2% of Zn % and, once harvested, their disposal does not appear
      to pose a problem for the environment. If heavy metals are present at high
      concentrations in the horizontal subsurface flow bed influent, over time, their
      accumulation in the filling medium could necessitate special care in the bed's
      management to avoid release into the surrounding environment.

PMID- 20692018
TI  - Production of phthalate esters by nuisance freshwater algae and cyanobacteria.
AB  - Phthalate esters are widely distributed pollutants which originate from synthetic
      plasticizer and are known to act as toxicants as well as environmental pheromones
      in the aquatic ecosystems. From investigating sixteen species of freshwater algae
      and cyanobacteria we revealed that some of them were capable of producing either
      di(n-butyl)phthalate (DBP) or mono(2-ethylhexyl)phthalate (MEHP) or both. These
      phthalate esters would be released into the environment under stress conditions.
      The incubation of the cells in culture medium containing NaH(13)CO(3) confirmed
      that both phthalates were de novo synthesized by the studied cells. This study
      suggested that the nuisance freshwater micro-algae and cyanobacteria growing in
      eutrophic waters might affect the aquatic ecosystem via the production of these
      phthalate esters.

PMID- 20692020
TI  - Which offers more scope to suppress river phytoplankton blooms: reducing nutrient
      pollution or riparian shading?
AB  - River flow and quality data, including chlorophyll-a as a surrogate for river
      phytoplankton biomass, were collated for the River Ouse catchment in NE England,
      which according to established criteria is a largely unpolluted network. Against
      these data, a daily river quality model (QUESTOR) was setup and successfully
      tested. Following a review, a river quality classification scheme based on
      phytoplankton biomass was proposed. Based on climate change predictions the model
      indicated that a shift from present day oligotrophic/mesotrophic conditions to a
      mesotrophic/eutrophic system could occur by 2080. Management options were
      evaluated to mitigate against this predicted decline in quality. Reducing
      nutrient pollution was found to be less effective at suppressing phytoplankton
      growth than the less costly option of establishing riparian shading. In the Swale
      tributary, ongoing efforts to reduce phosphorus loads in sewage treatment works
      will only reduce peak (95th percentile) phytoplankton by 11%, whereas a reduction
      of 44% is possible if riparian tree cover is also implemented. Likewise, in the
      Ure, whilst reducing nitrate loads by curtailing agriculture in the headwaters
      may bring about a 10% reduction, riparian shading would instead reduce levels by
      47%. Such modelling studies are somewhat limited by insufficient field data but
      offer a potentially very valuable tool to assess the most cost-effective methods
      of tackling effects of eutrophication.

PMID- 20692019
TI  - Effect of pest controlling neem and mata-raton leaf extracts on greenhouse gas
      emissions from urea-amended soil cultivated with beans: a greenhouse experiment.
AB  - In a previous laboratory experiment, extracts of neem (Azadirachta indica A.
      Juss.) and Gliricidia sepium Jacquin, locally known as mata-raton, used to
      control pests on crops, inhibited emissions of CO(2) from a urea-amended soil,
      but not nitrification and N(2)O emissions. We investigated if these extracts when
      applied to beans (Phaseolus vulgaris L.) affected their development, soil
      characteristics and emissions of carbon dioxide (CO(2)) and nitrous oxide (N(2)O)
      in a greenhouse environment. Untreated beans and beans planted with lambda
      cyhalothrin, a commercial insecticide, served as controls. After 117days, shoots
      of plants cultivated in soil amended with urea or treated with lambda
      cyhalothrin, or extracts of neem or G. sepium were significantly higher than when
      cultivated in the unamended soil, while the roots were significantly longer when
      plants were amended with urea or treated with leaf extracts of neem or G. sepium
      than when treated with lambda-cyhalothrin. The number of pods, fresh and dry pod
      weight and seed yield was significantly higher when bean plants were treated with
      leaf extracts of neem or G. sepium treatments than when left untreated and
      unfertilized. The number of seeds was similar for the different treatments. The
      number of nodules was lower in plants fertilized with urea, treated with leaf
      extracts of neem or G. sepium, or with lambda-cyhalothrin compared to the
      unfertilized plants. The concentrations of NH(4)(+), NO(2)(-) and NO(3)(-)
      decreased significantly over time with the lowest concentrations generally found
      at harvest. Treatment had no significant effect on the concentrations of NH(4)(+)
      and NO(2)(-), but the concentration of NO(3)(-) was significantly lower in the
      unfertilized soil compared to the other treatments. It was found that applying
      extracts of neem or G. sepium leaves to beans favored their development when
      compared to untreated plants, but had no significant effect on nitrification in
      soil.

PMID- 20692021
TI  - Fine particle collection of an electrostatic precipitator in CO2-rich gas
      conditions for oxy-fuel combustion.
AB  - The collection of particles in CO(2)-enriched environments has long been
      important for the capture of CO(2) in order to clean gases via oxy-fuel
      combustion. We here report on the collection characteristics of fine and
      ultrafine particles using an electrostatic precipitator (ESP) in a CO(2)-enriched
      atmosphere. In order to understand the characteristics of particle collection in
      CO(2)-rich gas mixtures, the ionic properties of a CO(2)-enriched atmosphere was
      also investigated. The electrical mobility of the ions in a CO(2)-enriched
      atmosphere was found to be about 0.56 times that found in a conventional air
      atmosphere, due to the higher mass of CO(2) gas compared to that of air. The low
      electrical mobility of ions resulted in a low corona current under CO(2)-enriched
      conditions. The collection efficiency of particles in a CO(2)-rich atmosphere for
      a given power consumption was thus somewhat lower than that found in air, due to
      the low quantity of particle charging in CO(2)-enriched air. At the same time,
      higher temperatures led to the higher electrical mobility of ions, which resulted
      in a greater collection efficiency for a given power. The presence of a negative
      corona also led to a greater collection efficiency of particles in an ESP than
      that achieved for a positive corona.

PMID- 20692022
TI  - Vitamin D receptor haplotypes affect lead levels during pregnancy.
AB  - Pregnant women are particularly susceptible to toxic effects associated with lead
      (Pb) exposure. Pb accumulates in bone tissue and is rapidly mobilized from bones
      during pregnancy, thus resulting in fetal contamination. While vitamin D receptor
      (VDR) polymorphisms modify bone mineralization and affect Pb biomarkers including
      blood (Pb-B) and serum (Pb-S) Pb concentrations, and %Pb-S/Pb-B ratio, the
      effects of these polymorphisms on Pb levels in pregnant women are unknown. This
      study aimed at examining the effects of three (FokI, BsmI and ApaI) VDR
      polymorphisms (and VDR haplotypes) on Pb levels in pregnant women. Pb-B and Pb-S
      were determined by inductively coupled plasma mass spectrometry in samples from
      256 healthy pregnant women and their respective umbilical cords. Genotypes for
      the VDR polymorphisms were determined by PCR and restriction fragment length
      digestion. While the three VDR polymorphisms had no significant effects on Pb-B,
      Pb-S or %Pb-S/Pb-B ratio, the haplotype combining the f, a, and b alleles for the
      FokI, ApaI and BsmI polymorphisms, respectively, was associated with
      significantly lower Pb-S and %Pb-S/Pb-B (P<0.05). However, maternal VDR
      haplotypes had no effects on Pb levels in the umbilical cords. To our knowledge,
      this is the first study showing that a combination of genetic polymorphisms
      (haplotype) commonly found in the VDR gene affects Pb-S and %Pb-S/Pb-B ratios in
      pregnant women. These findings may have major implications for Pb toxicity
      because they may help to predict the existence of a group of subjects that is
      genetically less prone to Pb toxicity during pregnancy.

PMID- 20692023
TI  - Hexavalent chromium in house dust--a comparison between an area with historic
      contamination from chromate production and background locations.
AB  - In contrast to Cr(+3), Cr(+6) is carcinogenic and allergenic. Although Cr(+6) can
      occur naturally, it is thought that most soil Cr(+6) is anthropogenic, however,
      the extent of Cr(+6) in the background environment is unknown. Cr(+6)-containing
      chromite ore processing residue (COPR) from chromate manufacture was deposited in
      numerous locations in Jersey City (JC), New Jersey. In the 1990's, significantly
      elevated concentrations of total Cr (Cr(+6)+Cr(+3)) were found in house dust near
      COPR sites. We undertook a follow-up study to determine ongoing COPR exposure. We
      compared Cr(+6) in house dust in JC to selected background communities with no
      known sources of Cr(+6). Samples were collected from living areas, basements and
      window wells. Cr(+6) was detected in dust from all JC and background houses. In
      the JC homes, the mean (+ or - SD) Cr(+6) concentration for all samples was 3.9 +
      or - 7.0 microg/g (range: non-detect-90.4 microg/g), and the mean Cr(+6) loading
      was 5.8 + or - 15.7 microg/m(2) (range: non-detect-196.4 microg/m(2)). In
      background homes, the mean Cr(+6) concentrations of all samples was 4.6 + or -
      7.8 microg/g, (range, 0.05-56.6 microg/g). The mean loading was 10.0 + or - 27.9
      microg/m(2) (range, 0.22-169.3 microg/m(2)). There was no significant difference
      between Cr(+6) dust concentrations in Jersey City and background locations.
      Stratification by sample location within houses and sampling method gave similar
      results. Samples exceeding 20 microg/g were obtained only from single wood
      surfaces in different homes. Lower concentrations in window well samples suggests
      transport from outside is not the major source of indoor Cr(+6). Landscaping and
      groundcover may influence indoor Cr(+6). There appears to be a widespread low
      level background of Cr(+6) that is not elevated in Jersey City homes despite its
      historic COPR contamination. It is possible that house dust, in general, is a
      source of Cr(+6) exposure with potential implications for persistence of chromium
      allergic contact dermatitis.

PMID- 20692024
TI  - Evaluation of the particle measurement programme (PMP) protocol to remove the
      vehicles' exhaust aerosol volatile phase.
AB  - European regulation for Euro 5/6 light duty emissions introduced the measurement
      of non-volatile particles with diameter >23 nm. The volatile phase is removed by
      using a heated dilution stage (150 degrees C) and a heated tube (at 300-400
      degrees C). We investigated experimentally the removal efficiency for volatile
      species of the specific protocol by conducting measurements with two Euro 3
      diesel light duty vehicles, a Euro 2 moped, and a Euro III heavy duty vehicle
      with the system's heaters on and off. The particle number distributions were
      measured with a Scanning Mobility Particle Sizer (SMPS) and a Fast Mobility
      Particle Sizer (FMPS). An Aerosol Mass Spectrometer (AMS) was used to identify
      the non-refractory chemical composition of the particles. A Multi-Angle
      Absorption Photometer (MAAP) was used to measure the black carbon concentration.
      The results showed that the condensed material in the accumulation mode (defined
      here as particles in the diameter range of approximately 50-500 nm) was removed
      with an efficiency of 50-90%. The (volatile) nucleation mode was also completely
      evaporated or was decreased to sizes <23 nm; thus these particles wouldn't be
      counted from the particle counter, indicating the robustness of the protocol.

PMID- 20692025
TI  - SGO White Paper on ovarian cancer: etiology, screening and surveillance.
AB  - Ovarian cancer is a heterogeneous, rapidly progressive, highly lethal disease of
      low prevalence. The etiology remains poorly understood. Numerous risk factors
      have been identified, the most prominent involving an inherited predisposition in
      10% of cases. Women with germline mutations associated with Hereditary
      Breast/Ovarian Cancer and Lynch syndromes have dramatically elevated risks (up to
      46% and 12%, respectively). Risk-reducing salpingo-oophorectomy is the best
      method to prevent ovarian cancer in these high-risk women. Significant risk
      reduction is also seen in the general population who use oral contraceptives.
      Since up to 89% patients with early-stage disease have symptoms prior to
      diagnosis, increased awareness of the medical community may facilitate further
      workup in patients who otherwise would have had a delay. Despite enormous effort,
      there is no proof that routine screening for ovarian cancer in either the high
      risk or general populations with serum markers, sonograms, or pelvic examinations
      decreases mortality. Further evaluation is needed to determine whether any novel
      biomarkers, or panels of markers, have clinical utility in early detection.
      Prospective clinical trials have to be designed and completed prior to offering
      of any of these new diagnostic tests. CA125 is currently the only biomarker
      recommended for monitoring of therapy as well as detection of recurrence. This
      commentary provides an overview on the background, screening and surveillance of
      ovarian cancer.

PMID- 20692026
TI  - Prescribing practices and asthma control with hydrofluoroalkane-beclomethasone
      and fluticasone: a real-world observational study.
AB  - BACKGROUND: Long-term randomized trials comparing asthma outcomes between inhaled
      corticosteroids in real-world populations are lacking. As such, rigorously
      conducted observational studies to complement the findings of randomized trials
      are needed. OBJECTIVE: We sought to compare asthma-related outcomes over 1 year
      as recorded in a large primary care database for patients aged 5 to 60 years
      receiving a first prescription (initiation population) or dose increase (step-up
      population) of hydrofluoroalkane (HFA)-beclomethasone or fluticasone. METHODS: We
      used a retrospective matched cohort study in which patients were matched on
      baseline demographic and disease severity measures. Coprimary outcomes were
      asthma control (a composite measure comprising no unplanned visit or
      hospitalization for asthma, oral corticosteroids, or antibiotics for lower
      respiratory tract infection) and exacerbation rate. RESULTS: More than 80% of
      patients in each population achieved asthma control; 10% and 16% of patients in
      the initiation and step-up populations, respectively, received add-on or
      combination therapy during the year. Fluticasone was prescribed at significantly
      higher doses than HFA-beclomethasone for both populations (P <or= .001). In the
      initiation population (n = 1319 in each cohort) the adjusted odds ratio for
      achieving asthma control with HFA-beclomethasone was 1.30 (95% CI, 1.02-1.65)
      relative to fluticasone. In the step-up population (cohorts: n = 250) the
      adjusted odds ratio for achieving asthma control with HFA-beclomethasone was 1.22
      (95% CI, 0.66-2.26). Exacerbation rates were similar between cohorts.
      CONCLUSIONS: In a real-world setting patients receiving HFA-beclomethasone had a
      similar or better chance of achieving asthma control at lower prescribed doses
      than with fluticasone.

PMID- 20692027
TI  - Are free light chain immunoglobulins related to nasal local allergic rhinitis?

PMID- 20692029
TI  - Dynamic monitoring of refractive index change through photoactive resins.
AB  - OBJECTIVES: The change in optical characteristics through the bulk of curing
      photopolymers is not fully understood. Photopolymerization processes are
      accompanied by photoinitiator absorption, density changes and volumetric
      shrinkage, which alter optical properties and affects curing efficiency through
      depth. METHODS: This investigation demonstrates the use of a novel low coherence
      interferometry technique for simultaneous measurement of optical (refractive
      index) and physical (shrinkage) properties throughout curing of photoactive
      monomers containing various concentrations of bisphenol-A-diglycidyl ether
      dimethacrylate and triethylene glycol dimethacrylate. RESULTS: Reliability of the
      interferometry technique was compared with an Abbe refractometer and showed a
      significant linear regression relationship (p<0.001; adjusted R(2)>0.99) for both
      uncured and cured resins. The extent and rate of refractive index change and
      magnitude of shrinkage strain was dependent upon monomer formulation.
      SIGNIFICANCE: The development of this interferometry technique provides a
      powerful non-invasive tool that will be useful for improving light transmission
      through photoactive resins and filled resin composites by precise control of
      optical properties through material bulk.

PMID- 20692030
TI  - Efficacy of pentavalent rotavirus vaccine against severe rotavirus
      gastroenteritis in infants in developing countries in sub-Saharan Africa: a
      randomised, double-blind, placebo-controlled trial.
AB  - BACKGROUND: Rotavirus gastroenteritis causes many deaths in infants in sub
      Saharan Africa. Because rotavirus vaccines have proven effective in developed
      countries but had not been tested in developing countries, we assessed efficacy
      of a pentavalent rotavirus vaccine against severe disease in Ghana, Kenya, and
      Mali between April, 2007, and March, 2009. METHODS: In our multicentre, double
      blind, placebo-controlled trial, undertaken in rural areas of Ghana and Kenya and
      an urban area of Mali, we randomly assigned infants aged 4-12 weeks without
      symptoms of gastrointestinal disorders in a 1:1 ratio to receive three oral doses
      of pentavalent rotavirus vaccine 2 mL or placebo at around 6 weeks, 10 weeks, and
      14 weeks of age. Infants with HIV infection were not excluded. Randomisation was
      done by computer-generated randomisation sequence in blocks of six. We obtained
      data for gastrointestinal symptoms from parents on presentation to health-care
      facilities and clinical data were obtained prospectively by clinicians. The
      primary endpoint was severe rotavirus gastroenteritis (Vesikari score >or=11),
      detected by enzyme immunoassay, arising 14 days or more after the third dose of
      placebo or vaccine to end of study (March 31, 2009; around 21 months of age).
      Analysis was per protocol; infants who received scheduled doses of vaccine or
      placebo without intervening laboratory-confirmed naturally occurring rotavirus
      disease earlier than 14 days after the third dose and had complete clinical and
      laboratory results were included in the analysis. This study is registered with
      ClinicalTrials.gov, number NCT00362648. FINDINGS: 5468 infants were randomly
      assigned to receive pentavalent rotavirus vaccine (n=2733) or placebo (n=2735).
      2357 infants assigned to vaccine and 2348 assigned to placebo were included in
      the per-protocol analysis. 79 cases of severe rotavirus gastroenteritis were
      reported in 2610.6 person-years in the vaccine group, compared with 129 cases in
      2585.9 person-years in the placebo group, resulting in a vaccine efficacy against
      severe rotavirus gastroenteritis of 39.3% (95% CI 19.1-54.7, p=0.0003 for
      efficacy >0%). Median follow-up in both groups was 527 days starting 14 days
      after the third dose of vaccine or placebo was given. 42 (1.5%) of 2723 infants
      assigned to receive vaccine and 45 (1.7%) of 2724 infants assigned to receive
      placebo had a serious adverse event within 14 days of any dose. The most frequent
      serious adverse event was gastroenteritis (vaccine 17 [0.6%]; placebo 17 [0.6%]).
      INTERPRETATION: Pentavalent rotavirus vaccine is effective against severe
      rotavirus gastroenteritis in the first 2 years of life in African countries with
      high mortality in infants younger than 5 years. We support WHO's recommendation
      for adoption of rotavirus vaccine into national expanded programmes on
      immunisation in Africa. FUNDING: PATH (GAVI Alliance grant) and Merck.

PMID- 20692031
TI  - Efficacy of pentavalent rotavirus vaccine against severe rotavirus
      gastroenteritis in infants in developing countries in Asia: a randomised, double
      blind, placebo-controlled trial.
AB  - BACKGROUND: Rotavirus vaccine has proved effective for prevention of severe
      rotavirus gastroenteritis in infants in developed countries, but no efficacy
      studies have been done in developing countries in Asia. We assessed the clinical
      efficacy of live oral pentavalent rotavirus vaccine for prevention of severe
      rotavirus gastroenteritis in infants in Bangladesh and Vietnam. METHODS: In this
      multicentre, double-blind, placebo-controlled trial, undertaken in rural Matlab,
      Bangladesh, and urban and periurban Nha Trang, Vietnam, infants aged 4-12 weeks
      without symptoms of gastrointestinal disorders were randomly assigned (1:1) to
      receive three oral doses of pentavalent rotavirus vaccine 2 mL or placebo at
      around 6 weeks, 10 weeks, and 14 weeks of age, in conjunction with routine infant
      vaccines including oral poliovirus vaccine. Randomisation was done by computer
      generated randomisation sequence in blocks of six. Episodes of gastroenteritis in
      infants who presented to study medical facilities were reported by clinical staff
      and from parent recollection. The primary endpoint was severe rotavirus
      gastroenteritis (Vesikari score >or=11) arising 14 days or more after the third
      dose of placebo or vaccine to end of study (March 31, 2009; around 21 months of
      age). Analysis was per protocol; infants who received scheduled doses of vaccine
      or placebo without intervening laboratory-confirmed naturally occurring rotavirus
      disease earlier than 14 days after the third dose and had complete clinical and
      laboratory results were included in the analysis. This study is registered with
      ClinicalTrials.gov, number NCT00362648. FINDINGS: 2036 infants were randomly
      assigned to receive pentavalent rotavirus vaccine (n=1018) or placebo (n=1018).
      991 infants assigned to pentavalent rotavirus vaccine and 978 assigned to placebo
      were included in the per-protocol analysis. Median follow up from 14 days after
      the third dose of placebo or vaccine until final disposition was 498 days (IQR
      480-575). 38 cases of severe rotavirus gastroenteritis (Vesikari score >or=11)
      were reported during more than 1197 person-years of follow up in the vaccine
      group, compared with 71 cases in more than 1156 person years in the placebo
      group, resulting in a vaccine efficacy of 48.3% (95% CI 22.3-66.1) against severe
      disease (p=0.0005 for efficacy >0%) during nearly 2 years of follow-up. 25 (2.5%)
      of 1017 infants assigned to receive vaccine and 20 (2.0%) of 1018 assigned to
      receive placebo had a serious adverse event within 14 days of any dose. The most
      frequent serious adverse event was pneumonia (vaccine 12 [1.2%]; placebo 15
      [1.5%]). INTERPRETATION: In infants in developing countries in Asia, pentavalent
      rotavirus vaccine is safe and efficacious against severe rotavirus
      gastroenteritis, and our results support expanded WHO recommendations to promote
      its global use. FUNDING: PATH (GAVI Alliance grant) and Merck.

PMID- 20692032
TI  - Rotavirus: realising the potential of a promising vaccine.

PMID- 20692033
TI  - The promotion of type 1 T helper cell responses to cationic polymers in vivo via
      toll-like receptor-4 mediated IL-12 secretion.
AB  - Cationic polymers with nucleic acid drug delivery ability are widely used in
      experimental and clinical studies. However, their interactions with the immune
      systems are rarely studied. In the present study, cationic polymers including
      PEI, polylysine, cationic dextran and cationic gelatin exhibited strong
      stimulation on Th1 response which was characterized by the induction of the
      proliferation of CD4(+) T cells and the secretion of Th1 related cytokines.
      Experiments performed on macrophages demonstrated that cationic polymers
      specifically stimulated the macrophage to secrete IL-12 which is one of the main
      Th1-inducing cytokines. The result that MyD88 inhibitor remarkably reduced the IL
      12 expression induced by cationic polymers suggested that this stimulation was
      mainly mediated by toll-like receptor (TLR) pathway. Additionally, cationic
      polymers could strongly inhibit LPS-induced TNF-alpha secretion in macrophages.
      This result implied that cationic polymers may interact with macrophages through
      TLR-4 which is the receptor of LPS. The following test of inhibiting IL-12
      expression stimulated by cationic polymers using TLR-4 antibody proved that the
      stimulation was mainly mediated by TLR-4. Data in the present study demonstrated
      that the stimulation ability of cationic polymer was related with its cationic
      degree and neutralizing cationic polymer with anionic polymer completely
      abrogated the stimulation effect. The molecular weight of the polymers also
      influenced their stimulation ability, larger molecular means stronger stimulation
      ability. In conclusion, the present study revealed that cationic polymers could
      promote Th1 responses in vivo via TLR-4 mediated IL-12 secretion and the
      molecular weight and cationic degree of the polymers determined the stimulation
      ability.

PMID- 20692034
TI  - Effect of controlled co-delivery of synergistic neurotrophic factors on early
      nerve regeneration in rats.
AB  - Present interventions to repair severed peripheral nerves provide slow and poor
      early axonal regeneration, which may cause unsatisfactory functional
      reinnervation. To improve early axonal regeneration in a 10 mm rat sciatic nerve
      gap model, we developed collagen nerve conduits loaded with the synergistically
      acting glial cell line-derived neurotrophic factor (GDNF) and nerve growth factor
      (NGF). For controlling the concomitant GDNF and NGF release, the collagen tubes
      were cross-linked by a dehydro-thermal treatment (110 degrees C; 20 mbar; 5 days)
      prior to impregnating the tubes with GDNF and NGF and by coating drug-loaded
      tubes with layers of poly(lactide-co-glycolide). The conduits made of cross
      linked collagen released low initial amounts of GDNF and NGF (2% of both during
      first 3 days) and enhanced significantly the early (2 weeks) nerve regeneration
      in terms of axonal outgrowth and Schwann cell migration in a 10 mm rat sciatic
      nerve gap model, as compared to the conduits made of non-cross-linked collagen
      releasing higher initial amounts of GDNF and NGF (12-16% within 3 days), or those
      releasing GDNF alone. The enhancement of early axonal regeneration using
      controlled co-delivery of multiple synergistic neurotrophic factors is an
      important requisite for eventually establishing functional connections with the
      target organ.

PMID- 20692035
TI  - LAIR2 localizes specifically to sites of extravillous trophoblast invasion.
AB  - PURPOSE: A global gene expression microarray analysis of surplus chorionic villus
      sampling (CVS) tissues identified leukocyte-associated immunoglobulin-like
      receptor 2 (LAIR2) as down-regulated in the first trimester of pregnancies
      destined for preeclampsia. Neither the localization nor the function of LAIR2 has
      been examined in the placenta. Localization studies were conducted in placental
      tissues to determine the precise sites of LAIR2 mRNA production and protein
      binding. RESULTS: Quantitative real time polymerase chain reaction (qRT-PCR)
      indicated LAIR2 expression in CVS, but none in breast, lymph node, kidney, skin,
      uterus, or third trimester placentas. In situ hybridization (ISH) revealed a
      highly restricted LAIR2 localization. LAIR2 mRNA was found only in the more
      distal portions of trophoblast anchoring cell columns, adjacent to the invading
      extravillous trophoblast (EVT). Immunohistochemistry (IHC) detected intracellular
      LAIR2 staining in these same cells. Extracellular staining of this soluble
      receptor was found in the acellular material between invasive EVT cells distal to
      the anchoring cell columns. CONCLUSIONS: ISH and IHC staining for LAIR2 detected
      specific, highly localized expression at the leading edge of EVT anchoring cell
      columns in first trimester placentas. This staining likely identifies the site of
      production for this soluble receptor. Following secretion, the receptor appears
      to bind extracellular material among the invasive EVT. The precise restriction of
      this protein only to the sites of EVT invasion strongly suggests that it
      functions to regulate this invasion. The decreased LAIR2 expression noted in
      first trimester placentas that ultimately developed preeclampsia further suggests
      that alterations in LAIR2 may play an etiologic role in preeclampsia.

PMID- 20692036
TI  - What are RBC-transfusion-dependence and -independence?
AB  - The term RBC-transfusion-dependence is widely-used by hematologists to describe a
      condition of severe anemia typically arising when erythropoiesis is reduced such
      that a person continuously requires >=1 RBC-transfusions over a specified
      interval. Defining a person as RBC-transfusion-dependent has important
      implications in diverse hematological disorders especially because it strongly
      correlated with decreased survival. Conversely, becoming RBC-transfusion
      independent or receiving fewer RBC-transfusions over a specified interval is
      defined as improvement or response in many disease- and/or therapy-setting.
      Whether this correlates with improved survival is controversial. We used a
      structured expert-panel consensus panel process to define RBC-transfusion
      dependence and -independence or improvement. We suggest these definitions may
      prove useful to persons studying or treating these diseases.

PMID- 20692037
TI  - The use of imatinib mesylate has no adverse effects on the heart function.
      Results of a pilot study in patients with chronic myeloid leukemia.
AB  - To investigate cardiac effects of imatinib at an extended follow-up (median 12.4
      months), 12 chronic myeloid leukemia patients underwent cardiac screening. No
      significant changes on the frequency of cardiovascular signs and symptoms,
      electrocardiographic abnormalities, echocardiographic measurements and BNP levels
      were observed. Median ejection fraction was 67% at baseline versus 68% at follow
      up (median intra-patient change 0.5%). Median BNP levels were 8.3 versus 7.3pg/mL
      (median intra-patient change 0.2pg/mL). Troponin I measures were below the lower
      limit of detection, whereas strain measures were similar to healthy control. This
      pilot study suggests that it is probably safe to perform cardiac monitoring on an
      annual basis.

PMID- 20692038
TI  - 'The shape of the human being as a function of time': time, transplantation, and
      tolerance in Peter Brian Medawar's research, 1937-1956.
AB  - Using tissue transplantation, the British scientist Peter Brian Medawar showed
      how extrinsic cells could be permanently integrated into an animal's body without
      provoking immune responses. With his study of this phenomenon--which he called
      'actively acquired tolerance'--Medawar was awarded the Nobel Prize in Medicine
      and Physiology in 1960 along with the Australian scientist Frank Macfarlane
      Burnet, who theoretically predicted the possibility. The monumental work of
      Medawar stems from his long and deep interest in the nature of living organisms'
      changes over time, such as growth, aging, and evolution. In particular, his
      concern for the phenomenon of decline played a critical role in his research
      design regarding tolerance and its interpretation.

PMID- 20692039
TI  - Binding of human antigen R (HuR) to an AU-rich element (ARE) in the
      3'untranslated region (3'UTR) reduces the expression of decay accelerating factor
      (DAF).
AB  - We have investigated the role of the 3'untranslated region (3'UTR) in the
      expression of decay accelerating factor (DAF), one of the major membrane
      regulators of Complement activation. We show here that the 3'UTR of DAF contains
      an adenylate uridine rich element (ARE) AUUUAUUUAUAUUUAUUUA, which belongs to
      Class II Cluster 4 of the AU-rich element-containing mRNA (ARED) database.
      Enhanced Green Fluorescent Protein (EGFP) Reporter constructs containing the DAF
      3'UTR showed reduced levels of expression when transfected into a variety of cell
      lines compared to 3'UTR reporter constructs without the ARE sequence.
      Furthermore, the inhibitor of mRNA transcription Actinomycin D had a much
      stronger effect on mRNA half-life of the ARE-containing 3'UTR demonstrating that
      this ARE destabilises the mRNA. Electrophoretic Mobility Shift Assays (EMSA)
      using biotinylated RNA probes, demonstrated that cytoplasmic Human antigen R
      (HuR) bound to the DAF ARE. Transfection experiments using HuR specific siRNA
      increased DAF expression whilst plasmids containing the coding sequence of HuR
      had the opposite effect, demonstrating that HuR reduced the stability of DAF mRNA
      and suggesting that it is of importance in regulating the expression of DAF.
      These data suggest that modulators of HuR could potentially be used to alter DAF
      expression and therefore increase the susceptibility of malignant cells to
      immunotherapy.

PMID- 20692040
TI  - Risk of placental abruption in relation to maternal depressive, anxiety and
      stress symptoms.
AB  - BACKGROUND: Little is known about the influence of psychiatric factors on the
      etiology of placental abruption (PA), an obstetrical condition that complicates 1
      2% of pregnancies. We examined the risk of PA in relation to maternal psychiatric
      symptoms during pregnancy. METHODS: This case-control study included 373 PA cases
      and 368 controls delivered at five medical centers in Lima, Peru. Depressive,
      anxiety and stress symptoms were assessed using the Patient Health Questionnaire
      (PHQ-9) and the Depression Anxiety Stress Scales (DASS-21). Multivariable
      logistic regression models were fit to calculate odds ratios (aOR) and 95%
      confidence intervals (CI) adjusted for confounders. RESULTS: Depressive symptoms
      of increasing severity (using the DASS depression subscale) was associated with
      PA (p for trend=0.02). Compared with women with no depressive symptoms, the aOR
      (95%CI) for PA associated with each level of severity of depression symptoms
      based on the DASS assessment were as follows: mild 1.84 (0.91-3.74); moderate
      1.25 (0.67-2.33); and severe 4.68 (0.98-22.4). The corresponding ORs for mild,
      moderate, and moderately severe depressive symptoms based on the PHQ assessment
      were 1.10 (0.79-1.54), 3.31 (1.45-7.57), and 5.01 (1.06-23.6), respectively. A
      positive gradient was observed for the odds of PA with severity of anxiety (p for
      trend=0.002) and stress symptoms (p for trend=0.002). LIMITATIONS: These cross
      sectionally collected data may be subject to recall bias. CONCLUSIONS: Maternal
      psychiatric disorders may be associated with an increased occurrence of AP.
      Larger studies that allow for more precise evaluations of maternal psychiatric
      health in relation to PA risk are warranted.

PMID- 20692043
TI  - Validity of the GAD-7 scale as an outcome measure of disability in patients with
      generalized anxiety disorders in primary care.
AB  - OBJECTIVE: To explore the validity of the GAD-7 scale as an outcome measure of
      disability in primary care. METHODS: A random sample of 212 subjects was
      recruited in primary care clinics; 50% diagnosed with generalized anxiety
      disorder (GAD) by DSM-IV criteria and 50% concurrent matched controls. The GAD-7,
      the Hamilton Anxiety Scale (HAM-A), and the abridged 12-item version of World
      Health Organization Disability Scale (WHO-DAS-II) were administered. The number
      of visits to primary care and specialty clinics was also recorded. RESULTS:
      Strong and significant (p<0.001) correlations were found between GAD-7 and HAM-A
      (r=0.852) and WHO-DAS-II (r=0.704) scores, particularly for Participation in
      Society (r=0.741), Understanding and Communication (r=0.679), and Life Activities
      (0.638) dimensions. Moderate but significant correlations were also found between
      GAD-7 score and the number of visits to Primary Care (r=0.393) and Specialty
      clinics (r=0.373). In all cases, an overall relation was observed between GAD-7
      severity levels and disability scores [F (3,208)=25.4, p<0.001] as assessed by
      the WHO-DAS II, with higher mean disability values related to higher severity
      levels. CONCLUSIONS: The GAD-7 scale has been shown to highly correlate not only
      with specific anxiety but also with disability measures. It has been shown that
      more severe GAD levels correlate with higher disability states and tend to demand
      more health care attention. As the GAD-7 is self-administered and is not time
      consuming, this instrument could be a good choice to explore the level of patient
      disability in subjects with GAD in primary care settings.

PMID- 20692042
TI  - A pilot study of acupuncture augmentation therapy in antidepressant partial and
      non-responders with major depressive disorder.
AB  - BACKGROUND: Acupuncture is widely used for treating major depressive disorder
      (MDD). There is evidence supporting acupuncture as an antidepressant monotherapy,
      but its efficacy as augmentation in antidepressant partial and non-responders has
      not been well-investigated. METHODS: Thirty subjects (47% female, mean age 48+/
      11 years) with a history of SCID-diagnosed MDD and partial or non-response after
      >=8 weeks of antidepressant therapy were assigned 8 weeks of standardized 30-min
      open acupuncture augmentation sessions on a weekly (n=24) or twice-weekly (n=6)
      basis. Change in the Hamilton-D-17 score was the primary outcome measure, and
      response rates (based on HAM-D-17 score improvement of >=50%) the secondary
      outcome. RESULTS: Twenty subjects (40% female; 18 in weekly and 2 in twice-weekly
      treatment) completed the study. In the intent-to-treat (ITT) sample (N=30), HAM-D
      17 scores decreased from 18.5+/-3.8 to 11.2+/-5.3 in the weekly group (p<0.001),
      and from 18.5+/-3.3 to 11.8+/-4.8 in the twice-weekly group (p=0.03). Improvement
      did not differ significantly between treatment arms (p=0.76). Response rates were
      47% for all ITT subjects, 50% for the weekly group and 33% for the twice-weekly
      group (p=0.66). The most common side effects included soreness/pain (n=7),
      bruising (n=4), and mild bleeding (n=1) at the needle site. One subject
      discontinued because of side effects (pain). LIMITATIONS: Open design, small
      sample, polypharmacy with antidepressants. CONCLUSIONS: Once or twice-weekly
      acupuncture augmentation was safe, well-tolerated and effective in antidepressant
      partial and non-responders, suggesting good feasibility in outpatient settings.
      Replication in controlled trials is warranted.

PMID- 20692041
TI  - Long chain n-3 fatty acids intake, fish consumption and suicide in a cohort of
      Japanese men and women--the Japan Public Health Center-based (JPHC) prospective
      study.
AB  - OBJECTIVE: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been
      implicated as protective against suicide. However, it is uncertain whether a
      higher intake of EPA and DHA or of fish, a major source of these nutrients,
      lowers suicidal risk among Japanese, whose fish consumption and suicide rate are
      both high. This study prospectively examined the relation between fish, EPA, or
      DHA intake and suicide among Japanese men and women. METHOD: Subjects were 47,351
      men and 54,156 women aged 40-69 years who participated in the JPHC Study,
      completed a food frequency questionnaire in 1995-1999, and were followed for
      death through December 2005. We used the Cox proportional hazards regression
      model to estimate the hazard ratio (HR) and 95% confidence interval (CI) for
      suicide by quintile of intake. RESULTS: A total of 213 and 85 deaths from suicide
      were recorded during 403,019 and 473,351 person-years of follow-up for men and
      women, respectively. Higher intakes of fish, EPA, or DHA were not associated with
      a lower risk of suicide. Multivariate HRs (95% CI) of suicide death for the
      highest versus lowest quintile of fish consumption were 0.95 (0.60-1.49) and 1.20
      (0.58-2.47) for men and women, respectively. A significantly increased risk of
      suicidal death was observed among women with very low intake of fish, with HRs
      (95% CI) for those in 0-5th percentile versus middle quintile of 3.41 (1.36
      8.51). CONCLUSIONS: Our overall result does not support a protective role of
      higher intake of fish, EPA, or DHA against suicide in Japanese men and women.

PMID- 20692044
TI  - Defense style in panic disorder before and after pharmacological treatment.
AB  - Whether or not the use of maladaptive defense style is a trait, as opposed to a
      state dependent phenomenon, in panic disorder (PD) is a topic still very much up
      for debate. The aim of the study was to verify whether PD patients, both before
      and after treatment, used different defense style than the control group. Sixty
      one PD patients (recruited from an original sample of 90 patients) and 64 healthy
      controls were evaluated against the Structured Clinical Interview for DSM-IV
      disorders, the Symptoms Check List-90, the Hamilton Rating Scales for Anxiety and
      for Depression and finally the Defense Style Questionnaire-40 (DSQ). The patients
      were treated with paroxetine or citalopram and were evaluated monthly for one
      year to assess the remission. The DSQ was re-administered to the patients at the
      end of the study. Before treatment, PD patients used more neurotic and immature
      forms of defense than controls. After treatment, those in remission used the same
      defense styles as the control group, whereas non-remitters still used more
      immature defenses. However, all the aforementioned difference disappeared, after
      excluding the effect of symptom severity. Our data supports the hypothesis that
      the use of maladaptive defenses might be the consequence of PD: when subjects
      fall ill, their capacity to use mature adaptive defenses may diminish, but when
      they recover their defensive style returns to a greater maturity. The present
      results are however limited by the dropout rate (one third of patients did not
      complete the study) and the use of just one questionnaire to evaluate the
      complexity of defense styles.

PMID- 20692045
TI  - Association study of microsatellite markers on chromosome 22q11-13 with
      schizophrenia and mood disorder in Chinese Han population.

PMID- 20692046
TI  - Bipolar disorder co-morbidity in children with attention deficit hyperactivity
      disorder.
AB  - The present study aimed at: (1) exploring rate and clinical features of
      superimposed bipolar disorder (BD) in Italian children with attention deficit
      hyperactivity disorder (ADHD), compared with a community sample, matched for age
      and gender; (2) exploring predictors of BD in ADHD children, by comparing ADHD
      children with or without superimposed BD. We studied 173 consecutive drug-naive
      outpatients with ADHD (156 males and 17 females, mean age of 9.2 +/- 2.3years,
      age range 6-17.5 years), diagnosed with a clinical interview (Schedule for
      Affective Disorders and Schizophrenia for School-Age Children-Present and
      Lifetime Version (K-SADS-PL)); the control group consisted of a community-based
      sample of 100 healthy children. The rate of children with a diagnosis of BD was
      higher in the ADHD group (29/173, 16.7%) compared with controls (1/100, 1%),
      (P<0.001). Among the 29 children with ADHD+BD, 16 (55.2%) had a Bipolar Disorder
      Not Otherwise Specified (BD-NOS), and 11 (37.9%) showed ultrarapid cycling.
      Compared with children with ADHD without BD, they showed a higher rate of
      combined sub-type (21/29, 72.4%), a higher score at ADHD-Rating Scale (total
      score and hyperactivity subscale), higher rates of major depression, oppositional
      defiant disorder and conduct disorder. In summary, children with ADHD present a
      higher risk for developing a superimposed BD. The identification of clinical
      features with an increased risk of BD can improve diagnosis, prognosis and
      treatments.

PMID- 20692047
TI  - Are sedentary television watching and computer use behaviors associated with
      anxiety and depressive disorders?
AB  - Sedentary behaviors may be more common among persons with mental disorders and
      thereby result in poorer health outcomes. This study examined whether
      independently of general physical activity level, mental disorders are linked to
      two important examples of sedentary behavior: computer use and watching
      television. We used cross-sectional data from The Netherlands Study of Depression
      and Anxiety (NESDA). Our study sample consisted of 2353 participants (age 18-65)
      of whom 1701 had a current anxiety and/or depressive diagnosis and 652 were
      healthy controls. Anxiety and depression diagnoses were conducted using the DSM
      IV based Composite International Diagnostic Interview. Controlling for
      sociodemographics and physical activity level we found that persons with a major
      depressive disorder (MDD) spend significantly more leisure time using the
      computer. We found that persons with dysthymia, panic disorder and agoraphobia
      spend significantly more daily hours watching television compared to controls.
      This study illustrates that sedentary behaviors occur more frequently among
      persons with a mental disorder, independent of general physical activity level.

PMID- 20692048
TI  - The bovine spleen: interactions among splenic cell populations in the innate
      immunologic control of hemoparasitic infections.
AB  - Over the past several years, innate immunity has been recognized as having an
      important role as a front-line defense mechanism and as an integral part of the
      adaptive immune response. Innate immunity in cattle exposed to hemoparasites is
      spleen-dependent and age-related. In this review, we discuss general aspects of
      innate immunity and the cells involved in this aspect of the response to
      infection. We also provide examples of specific splenic regulatory and effector
      mechanisms involved in the response to Babesia bovis, an important tick-borne
      hemoparasitic disease of cattle. Evidence for the regulatory and effector role of
      bovine splenic monocytes and DC both in directing a type-1 response through
      interaction with splenic NK cells and gammadeltaT-cells will be presented.

PMID- 20692049
TI  - Induction of vascular endothelial growth factor receptor-3 mRNA in glial cells
      following focal cerebral ischemia in rats.
AB  - To identify whether vascular endothelial growth factor receptor (VEGFR)-3, a
      receptor for VEGF-C and VEGF-D, is involved in pathophysiology of stroke, we
      investigated the spatiotemporal regulation of VEGFR-3 mRNA after transient focal
      cerebral ischemia. Most of the increase in VEGFR-3 expression in the ischemic
      core could be attributed to brain macrophages, whereas VEGFR-3 in the peri
      infarct penumbra region was predominantly expressed in reactive astrocytes. A
      subpopulation of VEGFR-3-expressing brain macrophages was positive for NG2
      proteoglycan and showed proliferative activity. In addition, in vitro model of
      stroke revealed no significant induction of VEGFR-3 in activated microglial
      cells, indicating that infiltrating exogenous macrophages expressed VEGFR-3 after
      focal ischemia. These data suggest that VEGFR-3 may be involved in the glial
      reaction and possibly in the recruitment of monocytic macrophages during ischemic
      insults.

PMID- 20692050
TI  - Association to the Glypican-5 gene in multiple sclerosis.
AB  - Multiple sclerosis (MS) is an inflammatory, demyelinating disease affecting the
      central nervous system. MS-associated variants have been reported at both HLA and
      non-HLA loci, the latter including chromosome 13q31-32 and the Glypican-5 and
      Glypican-6 genes. In order to further explore the 13q31-32 region in MS, we
      genotyped 33 SNPs in 1355 Norwegian MS patients and 1446 Norwegian controls. An
      intronic SNP in the Glypican-5 gene (rs9523787) showed association with MS
      (p(corr)=0.006). Thus, this study supports that MS susceptibility at 13q31-32 may
      localize to the Glypican-5 gene, which should lead to further fine-mapping,
      replication and functional studies of this gene.

PMID- 20692051
TI  - Interventions in health care professionals to improve treatment in children with
      upper respiratory tract infections.
AB  - OBJECTIVE: To analyse which strategies are used to promote evidence based
      interventions in the management of children with upper respiratory tract
      infections (URTIs) in daily practice. To assess the effectiveness of these
      interventions, and when more are effective--which works best. And to analyse the
      costs associated with these interventions. METHODS: We systematically searched
      Pubmed, Embase and CENTRAL bibliographies for studies on the effectiveness of
      strategies aimed at changing health care professionals' behavior in the
      management of children with URTIs. RESULTS: The search yielded 11,788 references,
      of which 18 studies were eligible, and 10 met the inclusion criteria. Most
      strategies were aimed at changing antibiotic prescribing behavior in children
      with acute otitis media. All strategies used (i.e. computer interventions,
      educational sessions with or without education materials, collaborative
      development of guidelines and a training video in combination with a risk factor
      checklist) were effective in changing health care professionals practice
      regarding children with URTIs. Multifaceted and computer strategies work best.
      Computer interventions reduced antibiotic prescribing by 4% and 34% and increased
      guideline compliance by 41%. Educational sessions combined with education
      materials reduced inappropriate antibiotic prescription by 2% and 17% and
      increased knowledge of compliance enhancing strategies by 28% and 29%.
      Collaborative guideline development combined with educational materials reduced
      inappropriate antibiotic prescription by 24% and 40%. Finally, by a combination
      of a training video and a risk factor checklist appropriate referrals by the GP
      to the otolaryngologist increased by 37%. Since the costs associated with the
      interventions were not explicitly mentioned in the articles, no conclusion on
      cost-effectiveness can be drawn. CONCLUSION: Multifaceted and computer strategies
      appear to be most effective to put evidence into practice in the area of URTIs in
      children.

PMID- 20692052
TI  - Comparative biological effects and potency of 17alpha- and 17beta-estradiol in
      fathead minnows.
AB  - 17beta-Estradiol is the most potent natural estrogen commonly found in
      anthropogenically altered environments and has been the focus of many
      toxicological laboratory studies. However, fewer aquatic toxicological data on
      the effects of 17alpha-estradiol, a diastereoisomer of 17beta-estradiol, exists
      in the literature even though it has been found in the aquatic environment,
      sometimes at higher concentrations than 17beta-estradiol. The central objective
      of this study was to determine how the anatomical, physiological, and behavioral
      effects of exposure to 17alpha-estradiol compare to the well-documented effects
      of 17beta-estradiol exposures in aquatic vertebrates. A 21-day flow-through
      exposure of mature male and female fathead minnows to three concentrations each
      of 17alpha- and 17beta-estradiol (averaged measured concentrations 27, 72, and
      150 ng/L for 17alpha-estradiol, and 9, 20, and 44 ng/L for beta-estradiol,
      respectively) yielded significant, concentration-dependent differences in plasma
      vitellogenin concentrations among estradiol-exposed males when compared to fish
      from an ethanol carrier control. Interstitial cell prominence in the testis of
      fish was elevated in all estradiol treatments. Aggressiveness of male fish to
      defend nest sites appeared depressed in many of the higher concentration
      estradiol treatments (albeit not significantly). No clear effects were observed
      in female fish. Based on plasma vitellogenin data, it appears that 17beta
      estradiol is 8-9 times more potent than 17alpha-estradiol and that the lowest
      observable effect concentration (LOEC) for 17alpha-estradiol in fathead minnows
      is greater than 25 ng/L and may be less than 75 ng/L.

PMID- 20692053
TI  - Waterborne fluoxetine disrupts feeding and energy metabolism in the goldfish
      Carassius auratus.
AB  - Fluoxetine (FLX) is one of the most commonly detected pharmaceuticals in
      wastewater and bioaccumulates in wild-caught fish, especially in brain, liver and
      muscle tissues. Previous studies indicated that FLX is pharmacologically active
      in fish species exerting anorexigenic effects, but it is not clear whether
      waterborne FLX has any potential effects on regulating food intake and energy
      metabolism. In this study, we investigated the effect of two doses of FLX, an
      environmental concentration of 540 ng/L, and 100-times this concentration (54
      MUg/L), on feeding and key metabolic parameters in goldfish. Fish were exposed
      for a period of 28 days and changes in food intake and body mass were assessed.
      Pair-fed groups were maintained to discern primary FLX-induced effects from
      secondary metabolic responses induced by the decreased food intake. Additionally,
      an untreated control group and a fasted group were used to further compare
      physiological changes in the context of nutritional status of the animals.
      Significant decreases in food intake and weight gain were recorded in goldfish
      exposed to 54 MUg/L FLX. Furthermore a significant decrease occurred in
      circulating glucose levels in the group exposed to 540 ng/L FLX. To elucidate
      potential mechanisms, we investigated gene expression of feeding neuropeptides in
      the neuroendocrine brain of goldfish as well as gene expression and enzymatic
      activity of glycolytic and gluconeogenetic enzymes in liver and muscle tissues.
      The results confirm brain gene expression patterns in line with potential
      anorexigenic effects in the hypothalamus, with increased expression in
      corticotropin-releasing factor (CRF) and decreased expression of neuropeptide Y
      (NPY). With respect to glucose metabolism, liver gene expression of the
      gluconeogenic enzyme fructose-1,6-bisphosphatase decreased and muscle hexokinase
      activity increased in fish exposed to 540 ng/L FLX. Overall, this study
      demonstrated anorectic properties of FLX at a dose of 54 MUg/L FLX and moderate
      but significant effects on glucose metabolism in goldfish exposed to 540 ng/L
      FLX. Future studies investigating the importance of these changes in fish are
      warranted.

PMID- 20692054
TI  - Time course of markers of tissue repair after ablation of atrial fibrillation and
      their relation to left atrial structural changes and clinical ablation outcome.
AB  - BACKGROUND: Radiofrequency ablation of atrial fibrillation (AF) creates left
      atrial (LA) tissue damage with a subsequent healing process. We sought to
      prospectively assess the time course of biomarkers of tissue repair after
      ablation and to evaluate their association with clinical variables. METHODS: 30
      consecutive patients (57.9 +/- 1.7 yrs, 63% males) with paroxysmal AF underwent a
      CARTO-guided LA circumferential ablation, Lasso-guided segmental pulmonary vein
      isolation and ablation of complex fractionated atrial electrograms. Matrix
      metalloproteinase-9 (MMP-9) and transforming growth factor-beta1 (TGF-beta1),
      both key regulators of tissue repair, and the aminoterminal propeptide of type
      III procollagen (PIIINP), reflecting collagen synthesis, were determined in blood
      samples before and 6h, 1, 2, 7, 30, 90 and 180 days post-ablation. RESULTS: All
      markers showed a significant ablation-induced up-regulation (MMP-9: 1.8 +/- 0.1
      fold, TGF-beta1: 2.4 +/- 0.4-fold, PIIINP: 1.3 +/- 0.1-fold). MMP-9 was
      significantly up-regulated until day 90, TGF-beta1 only on day 2. PIIINP
      increased from day 2 to 7. The area under the curve (AUC) of MMP-9 and TGF-beta1
      correlated with the ablation-induced reduction of LA volume (both p<0.05). The
      AUC of MMP-9 was additionally associated with the amount of radiofrequency energy
      delivered during ablation (p < 0.05). At 12 months of follow-up 57% of patients
      were free of AF off antiarrhythmic drugs. The AUC of PIIINP independently
      predicted recurrent AF (p < 0.05). CONCLUSIONS: Markers of healing showed a
      significant up-regulation after AF ablation detectable for up to 90 days. A more
      pronounced up-regulation of MMP-9 or TGF-beta1 is associated with a greater
      reduction of LA size. High PIIINP levels after ablation predict a poor ablation
      outcome.

PMID- 20692055
TI  - Free fatty acids induce endothelial dysfunction and activate protein kinase C and
      nuclear factor-kappaB pathway in rat aorta.
AB  - BACKGROUND: Insulin resistance is associated with an inappropriate elevation of
      plasma free fatty acids (FFAs) and endothelial dysfunction. In this study, we
      asked if elevated circulating FFA levels led to impaired insulin signaling and
      endothelial dysfunction in-vivo via activation of PKC-mediated inflammatory
      pathways. METHODS: Sprague-Dawley (S-D) rats were infused with 1) 20%
      intralipid+heparin (FFA group) or 2) saline alone (Control group) for 6h. The
      intact aorta thoracica and aorta abdominalis were then removed. Aortic rings were
      isolated and evaluated for endothelial-dependent and non-dependent relaxation in
      an organ bath. The activities of eNOS and PKC were measured in endothelial
      homogenates prepared from endothelial cells harvested from the aorta. The
      expression levels of insulin signaling molecules IRS-1, Akt, eNOS, ERK1/ERK2, PKC
      alpha, NFkappaB-p65 subunit and IkappaB-alpha in rat aortic endothelium were
      determined by immunohistochemistry and Western blot. RESULTS: Elevation of FFAs
      resulted in a 35.9% reduction in the response to acetylcholine (p < 0.01), a 26%
      decline in plasma NOx levels (p < 0.05), a 53% decrease in eNOS activity and a 34
      +/- 9% inhibition in IRS-1 tyrosine phosphorylation (p < 0.05). We also found a
      46% decrease in Akt phosphorylation and a 36% decrease in eNOS phosphorylation.
      FFA-induced endothelial insulin resistance was associated with 82% increase in
      total membrane-associated PKC activity, a 1.7-fold increase in total PKC-alpha
      protein, 1.29-fold decrease in IkappaB-alpha expression levels and 1.47-fold
      increase in NF-kappaB p65 subunit expression in rat aortic endothelium.
      CONCLUSION: The molecular mechanisms underlying FFA-induced endothelial insulin
      resistance and eNOS inhibition may provide an important link implicating the PKC
      and IkappaB-alpha/NF-kappaB pathways in FFA-mediated inhibition of vascular
      insulin signaling.

PMID- 20692056
TI  - Cardioprotective effect of dexrazoxane in a rat model of myocardial infarction:
      anti-apoptosis and promoting angiogenesis.
AB  - OBJECTIVES: Dexrazoxane (DZR) is a clinically approved agent for preventive
      treatment of doxorubicin-induced cardiotoxicity. The objective of this study was
      to investigate the cardioprotective effects of DZR in a rat model of myocardial
      infarction (MI). METHODS: Sprague-Dawley rats were randomly divided into four
      groups: MI (n = 16), MI + DZR (n = 16), SHAM-operated (n = 14) and DZR-only (n =
      9). MI animals were subjected to left anterior descending coronary artery
      ligation. DZR was administered as a single dose at 125 mg/kg intraperitoneally.
      Four weeks after treatment, cardiac function by echocardiography, infarct size,
      capillary density in the infarct border zone, bone marrow-derived endothelial
      progenitor cells (EPCs), and cardiac expression of Bax were measured. RESULTS:
      Our results demonstrated that MI animals had compromised heart parameters. DZR
      treatment in MI animals resulted in reduction in infarct size (P = 0.013) and
      improved cardiac functions in terms of fractional shortening (P = 0.004) and
      ejection fraction (P = 0.004). The capillary density (P = 0.008) and bone marrow
      derived EPCs (P < 0.05) were higher in the MI + DZR group than those in the
      untreated MI group. Bax expression was down-regulated in heart tissues of MI +
      DZR animals (P = 0.043). CONCLUSIONS: Our study demonstrated that DZR exerted a
      cardioprotective effect in the rat model of MI, and the mechanism might be
      associated with anti-apoptosis and increased neovascularization.

PMID- 20692057
TI  - A prospective study evaluating duration of swine breeding herd PRRS virus-free
      status and its relationship with measured risk.
AB  - A variety of methods for eliminating the PRRS virus from pig production sites
      have been successfully applied. However, success in maintaining a PRRS virus-free
      status for extended periods of time following elimination has been inconsistent
      and unpredictable. The objective of this study was to evaluate whether risks
      measured using version 1 of the American Association of Swine Veterinarians
      (AASV) PRRS Risk Assessment for the Breeding Herd, season of year and method by
      which swine breeding herd sites were established PRRS virus-free were associated
      with how long they retained their virus-free status. Thirty-three swine farrow-to
      wean breeding herd sites that were established as PRRS virus-free by either
      populating a new site with virus-free breeding animals or by completely
      depopulating the site and repopulating with PRRS virus-free breeding animals were
      enrolled in this study. Survival analysis, using the Cox proportional hazards
      model and Kaplan-Meier survival curves, was performed where the outcome was the
      duration of time PRRS virus-free breeding herd sites remained virus-free
      ("survived"). Covariates evaluated included the internal and external risk scores
      measured by the PRRS Risk Assessment for the Breeding Herd as well as the season
      and the method by which the site was established free of the PRRS virus. All but
      5 (15%) of the 33 sites became positive to the PRRS virus during the course of
      the study and approximately 40% became positive within 1 year from when they were
      established free of the PRRS virus. A higher external risk score was associated
      with a greater risk of becoming positive to the PRRS virus and shorter survival
      times. The internal risk score was not significantly associated with survival.
      Establishing breeding herd sites free of the PRRS virus in winter months
      (November through February) was associated with a greater risk of becoming
      positive to the PRRS virus and shorter survival times compared to those
      established in non-winter months. The association between the risk of becoming
      positive to the PRRS virus and the external risk score was confounded by the
      method the site was established PRRS virus-free.

PMID- 20692058
TI  - Control of cryptosporidiosis in neonatal calves: use of halofuginone lactate in
      two different calf rearing systems.
AB  - To date there is no effective treatment for bovine cryptosporidiosis. This study
      describes the use of halofuginone lactate in preventing cryptosporidiosis in
      naturally infected neonatal calves on a dairy farm with a high prevalence of
      infection. The animals were kept in two different calf rearing systems. A
      randomized double-blind trial was carried out with 32 naturally infected calves,
      divided into four groups. The two prophylactic halofuginone lactate treated
      groups were kept in either individual or group pens. Similarly, the animals
      receiving the placebo were housed in either individual pens or together in a
      large pen. A total of ten faecal samples were collected periodically during the
      28 days study from each calf and tested for the presence of Cryptosporidium spp.
      using microscopic and molecular methods. Generalized estimating equations models
      were used to determine if the effects of the various treatments and/or rearing
      systems on the presence of diarrhoea and infection were statistically
      significant. Further analysis (classification trees models) was carried out to
      explore possible risk factors for cryptosporidiosis and interactions between
      treatments and rearing systems. Halofuginone lactate was shown to be effective in
      reducing clinical signs of cryptosporidiosis and environmental contamination.
      However, the treatment did not delay the onset of diarrhoea and did not reduce
      the risk of infection amongst calves reared together in a highly contaminated
      environment. The use of halofuginone lactate in combination with good hygienic
      measures, such as rearing animals in clean individual pens, was the most
      effective method to reduce the risk of cryptosporidiosis amongst 7-13 days old
      calves. It was concluded that the control of the parasite could be achieved by
      the combination of using effective preventive drugs, such as halofuginone lactate
      and good animal husbandry procedures.

PMID- 20692059
TI  - A "shotgun" method for tracing the birth locations of sheep from flock tags,
      applied to scrapie surveillance in Great Britain.
AB  - Movement records are often used to identify animal sample provenance by retracing
      the movements of individuals. Here we present an alternative method, which uses
      the same identity tags and movement records as are used to retrace movements, but
      ignores individual movement paths. The first step uses a simple query to identify
      the most likely birth holding for every identity tag included in a database
      recording departures from agricultural holdings. The second step rejects a
      proportion of the birth holding locations to leave a list of birth holding
      locations that are relatively reliable. The method was used to trace the birth
      locations of sheep sampled for scrapie in abattoirs, or on farm as fallen stock.
      Over 82% of the sheep sampled in the fallen stock survey died at the holding of
      birth. This lack of movement may be an important constraint on scrapie
      transmission. These static sheep provided relatively reliable birth locations,
      which were used to define criteria for selecting reliable traces. The criteria
      rejected 16.8% of fallen stock traces and 11.9% of abattoir survey traces. Two
      tests provided estimates that selection reduced error in fallen stock traces from
      11.3% to 3.2%, and in abattoir survey traces from 8.1% to 1.8%. This method
      generated 14,591 accepted traces of fallen stock from samples taken during 2002
      2005 and 83,136 accepted traces from abattoir samples. The absence or ambiguity
      of flock tag records at the time of slaughter prevented the tracing of 16-24% of
      abattoir samples during 2002-2004, although flock tag records improved in 2005.
      The use of internal scoring to generate and evaluate results from the database
      query, and the confirmation of results by comparison with other database fields,
      are analogous to methods used in web search engines. Such methods may have wide
      application in tracing samples and in adding value to biological datasets.

PMID- 20692060
TI  - Does competition from ambulatory surgical centers affect hospital surgical
      output?
AB  - This paper estimates the effect of ambulatory surgical centers (ASCs) on hospital
      surgical volume using hospital and year fixed effects models with several
      robustness checks. We show that ASC entry only appears to influence a hospital's
      outpatient surgical volume if the facilities are within a few miles of each
      other. Even then, the average reduction in hospital volume is only 2-4%, which is
      not nearly large enough to offset the new procedures performed by an entering
      ASC. The effect is, however, stronger for large ASCs and the first ASCs to enter
      a market. Additionally, we find no evidence that entering ASCs reduce a
      hospital's inpatient surgical volume.

PMID- 20692061
TI  - More genomic resources for less-studied crops.
AB  - Many of the crop species considered to be minor on a global scale, yet are
      important locally for food security in the developing world, have remained less
      studied crops. Recent years have witnessed the development of large-scale genomic
      and genetic resources, including simple sequence repeat, single nucleotide
      polymorphism and diversity array technology markers, expressed sequence tags or
      transcript reads, bacterial artificial chromosome libraries, genetic and physical
      maps, and genetic stocks with rich genetic diversity, such as core reference sets
      and introgression lines in these crops. These resources have the potential to
      accelerate gene discovery and initiate molecular breeding in these crops, thereby
      enhancing crop productivity to ensure food security in developing countries.

PMID- 20692062
TI  - Test-retest reliability of the soleus H-reflex excitability measured during human
      walking.
AB  - The purpose of the study was to investigate with what accuracy the soleus H
      reflex modulation and excitability could be measured during human walking on two
      occasions separated by days. The maximal M-wave (Mmax) was measured at rest in
      the standing position. During treadmill walking every stimulus elicited an M-wave
      of 25 +/- 10% of Mmax in the soleus muscle and a supra-maximal stimulus elicited
      a maximal M-wave 60 ms after the first stimulus. Both Mmax during rest and during
      walking were later used for normalization. When normalized to resting Mmax, the
      peak reflex amplitude during walking was 5% lower on Day 2 than on Day 1 (p =
      .32). However, when the peak H-reflex was normalized to Mmax in every sweep, Day
      2 showed a significant 15% lower amplitude (p = .037). The same pattern was found
      for the mean H-reflex. Spearman's Rho was .92 when normalized to resting Mmax but
      .88 when normalized to Mmax in every sweep. The Pearson product was used to
      identify one participant at a time on Day 1 among all seven participants on Day
      2. For both normalization procedures 5 of 7 participants were identified by this
      test. Since 5 of 7 participants were recognized between days, it must be
      recommended to use 10-15 participants for training or intervention studies as far
      as the H-reflex pattern of modulation during movement is concerned.

PMID- 20692063
TI  - Effect of Saccharomyces cerevisiae inoculum size on wine fermentation aroma
      compounds and its relation with assimilable nitrogen content.
AB  - Different commercial Saccharomyces cerevisiae strains have been applied at the
      winemaking level, trying to establish a dominant population of selected strains
      from the start of fermentation and ensuring the complete consumption of sugars.
      Although a large population of active yeast cells can be introduced in the
      inoculated wines, resulting in a complete fermentation, this does not necessarily
      mean an improvement of the sensory characteristics of the wines. The impact of
      the size of the inocula in wine quality parameters has been very little studied,
      and in no case the nutrient balance of the grape must utilized was taken into
      account. In this work we present results obtained for wine aroma compounds at
      three inoculum levels (10(4), 10(5) and 10(6)cells/mL), and two different yeast
      assimilable nitrogen (YAN) in a white grape must, using two S. cerevisiae strains
      commonly used for winemaking. A significant effect in the final concentrations of
      higher alcohols, esters, fatty acids, free monoterpenes and lactones was
      attributed to the size of inoculum in both strains but not in an easily
      predictable way. However, a consistent increase of desired aroma compounds
      (esters, lactones and free monoterpenes), and a decrease of less desired
      compounds for white wine (higher alcohols and medium chain fatty acids), was
      shown at inoculum sizes of 10(5)cells/mL for both strains in real winemaking
      conditions. In a discriminant analysis six aroma compounds discriminate the three
      inoculum sizes for all wine samples: 1,8-terpine, hodiol I (trans-3,7-dimethyl
      1,5-octadiene-3,7-diol), isobutyl alcohol, iso C4 acid, ethyl C6 ester and C8
      acid.

PMID- 20692064
TI  - Accuracy of three different techniques for automatically estimating innervation
      zone location.
AB  - The purpose of this study was to compare the accuracy of the estimated
      innervation zone (IZ) locations obtained from cross-correlation, the minimum
      amplitude, and maximum center frequency criteria. Eight healthy men (mean+/-SD
      age=23.0+/-4.3 yrs) performed isometric muscle actions of the leg extensors, and
      15 separate bipolar surface electromyographic (EMG) signals were detected from
      the vastus lateralis. A custom software program was used to estimate the location
      of the IZ based on: (1) the EMG channel that demonstrated the lowest amplitude,
      (2) the EMG channel that showed the highest mean frequency, and (3) the EMG
      channel that demonstrated the lowest peak cross-correlation between the signals
      from adjacent channels. The IZ location estimates from the lowest amplitude and
      highest mean frequency criteria were accurate in only 43.75% and 7.5% of the
      cases, respectively. The accuracy of the cross-correlation-based method was 90%.
      The cross-correlation-based method was much more accurate for estimating IZ
      location than were the lowest amplitude and highest mean frequency criteria.
      Cross-correlation could potentially be used for estimating the location of the IZ
      without the need for visual inspection of EMG signals.

PMID- 20692065
TI  - "Awkward wording. Rephrase": linguistic injustice in ecological journals.

PMID- 20692066
TI  - Invasive group B streptococcal disease in an orthopaedic unit.
AB  - Invasive group B streptococcus (GBS) is an increasing cause of infection in
      orthopaedic patients. Risk factors include increasing age, diabetes mellitus and
      immune deficiency. It may cause native and periprosthetic joint sepsis,
      cellulitis, fasciitis, soft tissue abscesses and osteomyelitis. We describe the
      epidemiology and outcome from GBS infection in a large cohort of general
      orthopaedic patients. All those presenting to our institution with deep tissue or
      aspirate samples containing group B streptococcus over three years were
      identified and their case records examined retrospectively. There were 17 cases,
      giving an annual incidence of 0.69 per 100000 adult population. They comprised
      0.12% of all emergency admissions. Eight were related to joint prostheses, giving
      an incidence of 0.15% following joint replacement. Other infections related to
      underlying metalwork, osteomyelitis or chronic soft tissue infection. All the
      isolates were susceptible to benzylpenicillin, but six demonstrated intermediate
      resistance to macrolides. Sixteen patients required surgical debridement, and two
      ultimately required amputations. This study should raise awareness of GBS as a
      potential infectious agent in soft tissue and joint infections in patients with
      specific risk factors.

PMID- 20692067
TI  - Outbreak of severe sepsis due to contaminated propofol: lessons to learn.
AB  - Nosocomial infections are a frequent concern in healthcare. Despite the available
      knowledge on nosocomial infections and preventive measures, outbreaks of
      infections continue to occur. An outbreak of severe sepsis in patients who
      underwent minor procedures in an operating theatre during two consecutive days is
      described and analysed in this study. We performed a retrospective cohort study
      using epidemiological data in order to investigate the source of infection
      together with microbiological and on-site investigations and interviews. Seven
      patients met the case definition of postoperative systemic inflammatory response
      syndrome (SIRS). All other patients operated on over the same period served as
      controls. Of the risk factors investigated, general anaesthesia and propofol were
      statistically significant (P=0.003). Klebsiella pneumoniae and Serratia
      marcescens were cultured from opened vials of propofol, propofol-related devices
      and from blood cultures from two of the patients. These strains were
      genotypically indistinguishable. Lapses in aseptic preparation, handling and
      storage of the propofol were observed, and were the most probable cause of the
      extrinsic contamination. The daily procedure of handling propofol was not
      performed according to the manufacturer's recommendations, the main departure
      being the use of a single-use vial for multiple patients. This study documents
      the risk of infection due to contaminated propofol and the importance of having
      written guidelines for its handling.

PMID- 20692068
TI  - Unintended consequences and MRSA screening policy.

PMID- 20692069
TI  - Randomisation and sample size for clinical audit on infection control.
AB  - Clinical audit is both a part of clinical governance and an essential component
      of infection prevention and control. It is frequently performed on a proportion
      of the target population. The sample should represent the source population and
      be sufficient for statistical analysis. In a hospital, infection control
      practices are likely to be quite similar within the same clinical area (cluster
      effect). This must be taken into consideration when calculating the necessary
      number of patients. Sample size is determined by the desired level of precision
      for estimating the compliance rate, or by the difference between observed and
      expected rates, or on the difference before and after implementation of
      interventions. To estimate the hospital-wide compliance rate without additional
      costs we suggest focusing the audit on a large number of wards, even if fewer
      observations within each ward are obtained, rather than auditing a large number
      of practices on a restricted number of wards.

PMID- 20692070
TI  - Molecular epidemiology of multidrug-resistant Pseudomonas aeruginosa in a French
      university hospital.
AB  - The aim of this study was to assess the incidence and molecular epidemiology of
      multidrug-resistant (MDR) Pseudomonas aeruginosa in our university hospital.
      Analysis included antimicrobial susceptibility profiling, bla gene identification
      and pulsed-field gel electrophoresis (PFGE). During the one-year study, 654
      patients had at least one sample that tested positive for P. aeruginosa, of whom
      38 (5.8%) were colonised or infected with an MDR isolate, giving an incidence of
      0.1 patient per 1000 patient-days. The 38 non-duplicate isolates yielded 12
      different PFGE patterns, three of which included isolates from four patients and
      one of which included isolates from 15 patients. Two isolates produced acquired
      extended-spectrum beta-lactamase (one OXA-14 and one OXA-28). Genotyping showed
      that cross-transmission was responsible for about 70% of MDR P. aeruginosa cases
      although spatio-temporal analysis failed to demonstrate when this might have
      occurred for most cases. The major epidemic and the three main micro-epidemic
      clones were already present in our hospital with a more susceptible phenotype. It
      is likely that some P. aeruginosa clones are endemic in our hospital and that,
      within these clones, MDR isolates emerge under antibiotic pressure. Our results
      indicate that cross-transmission plays a major role in the spread of MDR P.
      aeruginosa and suggest that priority should be given to the improvement of
      standard hygienic precautions.

PMID- 20692071
TI  - Limiting risk of hospital adverse events: avoiding train wrecks is more important
      than counting and reporting them.
AB  - Targets implemented at national or state levels have been employed in response to
      excessive numbers of adverse events (AEs) such as multiple antibiotic-resistant
      Staphylococcus aureus bacteraemias. Hospital resources are limited and setting
      such targets can result in resource diversion to dealing with the targeted AEs.
      There may be initial success as judged by decreasing counts but underlying
      problems are not necessarily addressed, and there is evidence that other non
      targeted AEs may increase. Moreover, the values of individual observations can be
      greatly influenced by random variation. This can make it difficult using
      comparisons and targets to draw conclusions about the work of an institution.
      Although counting AEs is essential, the key to avoiding episodes of patient harm
      is prevention. This requires the implementation of evidence-based systems. These
      are already available for many AEs in the form of 'bundles' and checklists. When
      these systems are properly implemented and sustained, AE rates tend to occur at
      minimum predictable levels. Unfortunately, in spite of widespread knowledge and
      aggressive promotion, high levels of compliance have often been difficult to
      achieve and sustain. Better understanding and implementation of methods to
      sustain evidence-based systems are needed. Checklists, used as part of an overall
      system involving leadership and empowerment, application of evidence, culture
      change and measurement, may help to overcome this problem.

PMID- 20692072
TI  - Low incidence of arterial catheter infections in a Swedish intensive care unit:
      risk factors for colonisation and infection.
AB  - There is growing concern that arterial catheters (ACs) cause catheter-related
      infections (CRIs). Limited data are available concerning risk factors for AC-CRI
      and there are no studies concerning incidence and micro-organisms from northern
      Europe. The aims of this study were to determine the incidence of, and micro
      organisms responsible for, AC colonisation and AC-CRI in a Swedish intensive care
      unit (ICU), and to determine risk factors contributing to AC colonisation and AC
      CRI. We prospectively studied all patients (N=539) receiving ACs (N=691) in a
      mixed ICU of a county hospital. Six hundred (87%) of all ACs were assessed
      completely. The total catheterisation time for 482 patients was 2567 days. The
      incidence of positive tip culture was 7.8 per 1000 catheter-days, with the
      predominant micro-organism being coagulase-negative staphylococci (CoNS). The
      incidence of AC-CRI was 2.0 per 1000 catheter-days (with no cases of
      bacteraemia). All AC-CRIs were caused by CoNS. Multivariate analysis revealed
      that immunosuppression, central venous catheter (CVC) colonisation and CVC
      infection were significant risk factors for AC-CRI. We conclude that AC
      colonisation and infection with systemic symptoms occur at a low rate in our ICU
      which supports our practice of basic hygiene routines for the prevention of AC
      CRI. Colonisation and infection of a simultaneous CVC seem to be risk factors.
      The role of contemporaneous colonisation and infection of multiple bloodstream
      catheters has received little attention previously. Further studies are needed to
      verify the significance of this finding.

PMID- 20692073
TI  - Natural history of meticillin-resistant Staphylococcus aureus colonisation among
      residents in community long term care facilities in Spain.
AB  - The spread of meticillin-resistant Staphylococcus aureus (MRSA) is a major
      problem for both acute care hospitals and among residents in long term care
      facilities (LTCFs). We performed a cohort study to assess the natural history of
      MRSA colonisation in LTCF residents. Two cohorts of residents (231 MRSA carriers
      and 196 non-carriers) were followed up for an 18 month period, with cultures of
      nasal and decubitus ulcers performed every six months. In the MRSA carrier
      cohort, 110 (47.8%) residents had persistent MRSA colonisation for six months or
      longer, 44 (19.0%) had transient colonisation and nine (3.9%) were intermittently
      colonised. No risk factors for persistent MRSA colonisation could be determined.
      The annual incidence of MRSA acquisition was around 20% [95% confidence interval
      (CI): 14.3-25.5]. Antibiotic treatment was independently associated with MRSA
      acquisition (odds ratio: 2.27; 95% CI: 1.05-4.88; P=0.03). Just two clones were
      distinguishable by pulsed-field gel electrophoresis and multilocus sequence
      typing: CC5-MRSA IV, which is widely disseminated in Spanish hospitals, and ST22
      MRSA IV. This study adds to the knowledge of the epidemiology of MRSA in
      community LTCFs, which are important components of long term care in Spain.

PMID- 20692074
TI  - Accumulation of resident and peripheral dendritic cells in the aging CNS.
AB  - Dendritic cells (DC) are specialized antigen-presenting cells, responsible for
      peripheral immune responses. Recently, resident brain dendritic cells (bDC) were
      identified and functionally characterized in the young adult Itgax (CD11c) EYFP+
      transgenic mouse brain. In the present study, we describe changes in number,
      phenotype, and source of bDC in the aging mouse brain. Immunohistochemistry and
      fluorescent activated cell sorting (FACS) analysis revealed an age-related
      increase in bDC with a concomitant rise in the expression of immune activation
      markers MHCII, CD80, and CD86. Quantification of immunolabeled bDC in the cortex,
      corpus callosum, and cerebellum of the aged brain revealed a 2- to 5-fold
      increase. In contrast, either no change or a decrease in bDC was noted in regions
      of adult neurogenesis. Chimeras (wild type host/EYFP+ bone marrow) suggest that
      the increase of EYFP+ cells in the aging brain is in part due to an accumulation
      of peripherally derived cells. Collectively, the numerical and phenotypic changes
      in bDC indicate these cells may serve as an important immune component in the
      functional and anatomic alterations associated with aging.

PMID- 20692075
TI  - [Septic shock due to primary myonecrosis of psoas].

PMID- 20692076
TI  - [Malignant phyllodes tumor of the breast with lymph node metastases shown by FDG
      PET-CT].

PMID- 20692077
TI  - Lessons learned from measuring safety culture: an Australian case study.
AB  - BACKGROUND: adverse events in maternity care are relatively common but often
      avoidable. International patient safety strategies advocate measuring safety
      culture as a strategy to improve patient safety. Evidence suggests it is
      necessary to fully understand the safety culture of an organisation to make
      improvements to patient safety. AIM: this paper reports a case study examining
      the safety culture in one maternity service in Australia and considers the
      benefits of using surveys and interviews to understand safety culture as an
      approach to identify possible strategies to improve patient safety in this
      setting. SETTING: the study took place in one maternity service in two public
      hospitals in NSW, Australia. Concurrently, both hospitals were undergoing an
      organisational restructure which was part of a major health reform agenda. The
      priorities of the reform included improving the quality of care and patient
      safety; and, creating a more efficient health system by reducing administration
      inefficiencies and duplication. DESIGN: a descriptive case study using three
      approaches: FINDINGS: the safety culture was identified to warrant improvement
      across all six safety culture domains. There was reduced infrastructure and
      capacity to support incident management activities required to improve safety,
      which was influenced by instability from the organisational restructure. There
      was a perceived lack of leadership at all levels to drive safety and quality and
      improving the safety culture was neither a key priority nor was it valued by the
      organisation. CONCLUSION: the safety culture was complex as was undertaking this
      study. We were unable to achieve a desired 60% response rate highlighting the
      limitations of using safety culture surveys in isolation as a strategy to improve
      safety culture. Qualitative interviews provided greater insight into the factors
      influencing the safety culture. The findings of this study provide evidence of
      the benefits of including qualitative methods with quantitative surveys when
      examining safety culture. Undertaking research in this way requires local
      engagement, commitment and capacity from the study site. The absence of these
      factors is likely to limit the practicality of this approach in the clinical
      setting. SIGNIFICANCE: the use of safety culture surveys as the only method of
      assessing safety culture is of limited value in identifying strategies to
      potentially improve the safety culture.

PMID- 20692078
TI  - 'Lending the space': midwives' perceptions of birth space and clinical risk
      management.
AB  - OBJECTIVES: to explore and describe midwives perceptions of birth space and
      clinical risk management and their impact on practice both before and after a
      move to a new facility. DESIGN: an exploratory descriptive study utilising a
      modified participatory approach and observation and focus groups for data
      collection. SETTING: a major metropolitan maternity hospital in Victoria,
      Australia. PARTICIPANTS: 18 midwives, including graduate year midwives, caseload
      midwives and hospital midwives working normal shifts, employed within a hospital.
      FINDINGS: the major themes identified were perceptions of birth space,
      perceptions of risk management, influence of birth space and risk management on
      practice and moving but not changing: geographical space and practice. Midwives
      desire to create the ideal birth space was hampered by a prevailing biomedical
      discourse which emphasised risk. Midwives in all three groups saw themselves as
      the gatekeepers, 'holding the space' or 'providing a bridge' for women, often in
      the face of a hierarchical hospital structure with obstetricians governing
      practice. This situation did not differ significantly after the relocation to the
      new hospital. Despite a warmer, more spacious and private birth space midwives
      felt the care was still influenced by the old hierarchical hospital culture.
      Caseload midwives felt they had the best opportunity to make a difference to
      women's experience because they were able, through continuity of care, to build
      trusting relationships with women during the antenatal period. KEY CONCLUSIONS
      AND IMPLICATIONS FOR PRACTICE: although the physical environment can make a
      marginal contribution to an optimal birth space, it has little effect on clinical
      risk management practices within a major public hospital and the way in which
      this impacts midwives' practice. The importance of place and people are the key
      to providing an optimal birth space, as are women centred midwifery models of
      care and reasonable workloads.

PMID- 20692080
TI  - Management of poisonings: core curriculum 2010.

PMID- 20692079
TI  - Validation of CKD and related conditions in existing data sets: A systematic
      review.
AB  - BACKGROUND: Accurate classification of individuals with kidney disease is vital
      to research and public health efforts aimed at improving health outcomes. Our
      objective is to identify and synthesize published literature evaluating the
      accuracy of existing data sources related to kidney disease. STUDY DESIGN: A
      systematic review of studies seeking to validate the accuracy of the underlying
      data relevant to kidney disease. SETTING & POPULATION: US-based and international
      studies covering a wide range of both outpatient and inpatient study populations.
      SELECTION CRITERIA FOR STUDIES: Any English-language study investigating the
      prevalence or cause of kidney disease, existence of comorbid conditions, or cause
      of death in patients with chronic kidney disease (CKD). All definitions and
      stages of CKD, including end-stage renal disease (ESRD), were accepted. INDEX
      TESTS: Presence of a kidney disease-related variable in existing data sets,
      including administrative data sets and disease registries. REFERENCE TESTS:
      Presence of a kidney disease-related variable defined using laboratory criteria
      or medical record review. RESULTS: 30 studies were identified. Most studies
      investigated the accuracy of kidney disease reporting, comparing coded renal
      disease with that defined using estimated glomerular filtration rate. The
      sensitivity of coded renal disease varied widely (0.08-0.83). Specificity was
      higher, with all studies reporting values >=0.90. Studies evaluating the cause of
      CKD, comorbid conditions, and cause of death in patients with CKD used ESRD or
      transplant populations exclusively, and accuracy was highly variable compared
      with ESRD registry data. LIMITATIONS: Only English-language studies were
      evaluated. CONCLUSIONS: Given the heterogeneous results of validation studies, a
      variety of attributes of existing data sources, including the accuracy of
      individual data items within these sources, should be considered carefully before
      use in research, quality improvement, and public health efforts.

PMID- 20692081
TI  - Intimate partner violence and initiation of smoking and drinking: A population
      based study of women in Yokohama, Japan.
AB  - Intimate Partner Violence (IPV) is prevalent in the lives of women across the
      globe and has been found to be associated with substance use among women. As part
      of the World Health Organization's (WHO) cross-national research effort, this
      study examined the relationship between the experience of IPV and use of alcohol
      and tobacco among a probability sample of women aged 18-49 in Yokohama, Japan.
      Using retrospective data for 2000-2001, we employed methods of survival analysis
      that allowed an examination of the probability of initiating smoking and drinking
      subsequent to the experience of IPV. Experiencing IPV was associated with current
      smoking as well as initiation of smoking and current patterns of drinking. Women
      who had experienced IPV were more likely to be smoking at the time of the
      interview and tended to initiate smoking at earlier ages compared to those who
      had not experienced IPV. At any time point, the risk of starting to smoke was
      more than twice as high for women who had previously experienced IPV than for
      women who had not. In addition, women who had experienced IPV were more likely to
      drink heavily. The present study's findings clearly point to the need to enhance
      coordination between IPV prevention and substance abuse programs in order to
      improve the safety and wellbeing of women who have experienced IPV.

PMID- 20692082
TI  - Physical functioning among mid-life women: associations with trajectory of
      depressive symptoms.
AB  - During midlife, physical functioning limitations emerge and depressive symptoms
      are highly prevalent. We examined the relationship between physical functioning
      and depressive symptoms in the Michigan Study of Women's Health Across the Nation
      (SWAN) cohort of mid-life women (n = 377). Seven performance-based physical
      functioning measures quantifying strength, balance, coordination, flexibility and
      range of motion and perceived physical functioning, assessed with the SF-36
      physical functioning sub-score, were included. The Center for Epidemiological
      Studies Depression Scale (CES-D) identified concurrent depressive symptom
      trajectory from 2000/2001 through 2005/2006 and history of depressive symptoms
      from 1996/1997 through 1999/1900. Longitudinal mixed-effects regression modeling
      was used to evaluate relationships. Median age of participants was 50 years. As
      age increased, higher CES-D scores were associated with performance-based
      functions including slower timed walk sit-to-stand, and stair climb after
      adjusting for five-year history of depressive symptoms and relevant covariates.
      As age increased, those with higher CES-D scores were more likely to have
      perceived limitations in physical functioning, though the association was weak.
      History of depressive symptoms was not significant in any model. These findings
      suggest that higher concurrent depressive symptoms are modestly associated with
      slower movement and a perception of poorer functioning. In contrast, history of
      depressive symptoms played little or no role in current physical functioning of
      mid-life women. When evaluating physical function, women's current mental health
      status should be considered.

PMID- 20692084
TI  - Investing in health to improve the wellbeing of the disadvantaged: reversing the
      argument of Fair Society, Healthy Lives (the Marmot Review).

PMID- 20692083
TI  - Food, eating and taste: parents' perspectives on the making of the middle class
      teenager.
AB  - This paper reports findings from a qualitative study of views and understandings
      of dietary practices in middle class families. Thirty five parents/main food
      providers of boys and girls aged 13/14 years, living in Eastern Scotland, were
      interviewed about their and their teenagers' everyday lives, food, health and
      family practices. One of our aims was to understand more about the social and
      cultural conditions which might be promoting more positive dietary health and
      physical well-being amongst middle class families. Most parents' accounts
      appeared rooted in a taken-for-grantedness that family members enjoyed good
      health, lived in relatively secure and unthreatening environments regarding
      health and resources, and were able to lead active lives, which they valued.
      Although controlling teenagers' eating practices was presented as an ongoing
      challenge, active supervision and surveillance of their diets was described, as
      was guiding tastes in 'the right direction'. Parents described attempts to
      achieve family eating practices such as commensality, cooking from scratch, and
      encouraging a varied and nutritional 'adult' diet and cosmopolitan tastes, though
      work and activities could compromise these. These middle class families might be
      characterized as having future oriented 'hierarchies of luxury and choice', in
      which controlling and moulding teenagers' food practices and tastes was assigned
      a high priority.

PMID- 20692085
TI  - The Marmot Review - social revolution by stealth.

PMID- 20692086
TI  - Giant cell granuloma with aneurysmal bone cyst change within the mandible during
      pregnancy: a management dilemma.

PMID- 20692088
TI  - Multi-walled carbon nanotubes-ionic liquid-carbon paste electrode as a super
      selectivity sensor: application to potentiometric monitoring of mercury ion(II).
AB  - In this article a super selectivity potentiometric methodology, using an ion
      selective electrode, for determination of mercury ion(II) in aqueous solution was
      investigated. For modification of the electrode a room temperature ionic liquid,
      1-n-butyl-3-methylimidazolium tetrafluoroborate (BMIM.BF(4)), was applied as a
      super conductive binder, and Multi-walled carbon nanotubes (MWCNTs) was used in
      the composition of the carbon paste to improve conductivity and transduction of
      chemical signal to electrical signal. Moreover, incorporation of 1-(2
      ethoxyphenyl)-3-(3-nitrophenyl)triazene (ENTZ) as an ionophore to this
      composition caused to significantly enhanced selectivity toward Hg(II) ions over
      a wide concentration range of 1.0*10(-4) to 5.0*10(-9) M with a lower detection
      limit of 2.5*10(-9) M (0.5 ppb) and a Nernstian slope of 29.3+/-(0.2) mV decade(
      1) of Hg(II) activity. The electrode has a short response time (~5s) and can be
      used for at least 55 days without any considerable divergence in potentials, and
      the working pH range was 2.0-4.3. Finally, the proposed electrode was
      successfully used as an indicator for potentiometric determination of Hg(II) in
      dental amalgam and water samples.

PMID- 20692087
TI  - Notch signalling is required for the survival of epithelial stem cells in the
      continuously growing mouse incisor.
AB  - The Notch pathway regulates the renewal and fate decisions of stem cells in
      multiple tissues. Notch1, -2, as well as the Notch target gene Hes1 are expressed
      in the putative stem cells in the continuously growing mouse incisors, but so far
      there has not been any evidence for a function of the Notch pathway in the
      regulation of the incisor stem cells. We have analysed the effects of the Notch
      pathway inhibitor DAPT on the maintenance, proliferation, and differentiation of
      the epithelial stem cells in explant cultures of the mouse incisor. The proximal
      part of the incisor containing the cervical loop stem cell niche was dissected
      from newborn mice and cultured for 2-6 days in vitro. DAPT inhibited the
      expression of Notch target gene Hes1 in the cervical loop indicating that Notch
      signalling was inhibited in the putative stem cells. The most striking effect of
      DAPT was a significant reduction in the size of the cervical loop. DAPT caused a
      marked but partially reversible decrease in cell proliferation, as well as
      massive apoptosis in the epithelial stem cell niche. Interestingly, restricted
      apoptosis was detected within the Notch expressing putative stem cells also in
      the control cultures as well as in incisors in vivo, suggesting that apoptosis
      may be a mechanism regulating the size of the epithelial stem cell pool in the
      incisor. The differentiation of the epithelial cells into enamel-forming
      ameloblasts was not affected by DAPT but the number of preameloblasts was
      progressively decreased during culture period reflecting the depletion of stem
      and progenitor cells. Our results indicate that Notch signalling is required for
      epithelial stem cell survival and enamel formation in the continuously growing
      mouse incisor.

PMID- 20692089
TI  - Removal of hexavalent chromium by new quaternized crosslinked poly(4
      vinylpyridines).
AB  - New quaternized crosslinked poly(4-vinylpyridines) prepared by nucleophilic
      substitution reactions of 4-vinylpyridine: divinylbenzene copolymers of gel and
      porous structure with halogenated compounds such as benzyl chloride and 2
      chloracetone, were used to remove Cr(VI) from the aqueous solution. Batch
      adsorption studies were carried out to determine the effect of the initial
      concentration of Cr(VI), pH, temperature and the presence of sulfate anions. The
      process was found to be pH and concentration dependent. The adsorption capacities
      increase with the increase of the initial concentration of Cr(VI) and both resins
      exhibited the degrees of usage of the exchange capacities higher than 90% and
      good efficiency in the chromium removal. Equilibrium modeling of the process of
      Cr(VI) removal was carried out by using the Langmuir and Freundlich isotherms.
      The experimental data obeyed these isotherm models. The thermodynamic parameters
      (free energy change DeltaG, enthalpy change DeltaS and entropy change DeltaH) for
      the adsorption have been evaluated and therefore, it was showed the spontaneous
      and endothermic process of the adsorption of Cr(VI) on the pyridine resins. In
      the competitive adsorption studies, chromate/sulfate revealed the selectivity of
      the pyridine adsorbents towards chromium ions. At acidic pH the synthesized
      pyridine resins offer much greater chromate removal capacities compared to
      alkaline pH. In the competitive adsorption studies, chromate/sulfate revealed the
      selectivity of the pyridine adsorbents towards chromium ions due to the formation
      a sandwich arrangement with the chromium anion and functional groups attached to
      the quaternary nitrogen atom.

PMID- 20692090
TI  - Computational study of imidazole derivative as high energetic materials.
AB  - Density functional theory (DFT) calculations were performed for a series of
      imidazole derivatives. B3LYP and B3P86 functionals with 6-31G** basis set were
      used. Heats of formation (HOFs) were predicted through designed isodesmic
      reactions. Calculated results show that the HOFs relate to the number and the
      position of nitro groups. The HOFs increase with the augment of the number of the
      NO(2) group for the direct imidazole derivatives and decrease with the augment of
      the number of the NO(2) group for 1-picrylimidazole derivatives. Thermal
      stabilities were evaluated via bond dissociation energies (BDEs). The result
      shows that the increase of nitro group number on imidazole ring reduces the
      stability of the molecule. Further, the correlation was developed between impact
      sensitivity h(50) and the ratio (BDE/E) of the weakest bond BDE to the total
      energy E. The detonation performance data were also calculated.

PMID- 20692091
TI  - Adsorption of surfactant micelles and Cd2+/Zn2+ in micellar-enhanced
      ultrafiltration.
AB  - Micellar-enhanced ultrafiltration (MEUF) is a powerful treatment developed to
      remove heavy metals from wastewater. Efficient removal of Cd(2+)/Zn(2+) from
      wastewater was performed by MEUF using a polysulfone hollow ultrafiltration
      membrane, with sodium dodecyl sulfate (SDS) as the surfactant. The adsorption of
      surfactant micelles and Cd(2+)/Zn(2+) in MEUF was studied by changing the
      surfactant dosage and the Cd(2+)/Zn(2+) concentration in the feed. In addition,
      kinetics, adsorption isotherms, and thermodynamic rules were analyzed, and X-ray
      photoelectron spectroscopy (XPS) was conducted. It was found that when the
      Cd(2+)/Zn(2+) feed concentration was 50 mg/L, and the SDS dosage reached 2.15
      g/L, the concentration of heavy metal ions in the permeate stabilized at around 1
      4 mg/L, and the adsorption of Cd(2+)/Zn(2+) on SDS micelles followed second-order
      kinetics and the Langmuir isotherm laws. Adsorption is a spontaneous endothermic
      process in which the adsorption force is principally the attraction of opposite
      electrical charges.

PMID- 20692092
TI  - Numerical simulations of LNG vapor dispersion in Brayton Fire Training Field
      tests with ANSYS CFX.
AB  - Federal safety regulations require the use of validated consequence models to
      determine the vapor cloud dispersion exclusion zones for accidental liquefied
      natural gas (LNG) releases. One tool that is being developed in industry for
      exclusion zone determination and LNG vapor dispersion modeling is computational
      fluid dynamics (CFD). This paper uses the ANSYS CFX CFD code to model LNG vapor
      dispersion in the atmosphere. Discussed are important parameters that are
      essential inputs to the ANSYS CFX simulations, including the atmospheric
      conditions, LNG evaporation rate and pool area, turbulence in the source term,
      ground surface temperature and roughness height, and effects of obstacles. A
      sensitivity analysis was conducted to illustrate uncertainties in the simulation
      results arising from the mesh size and source term turbulence intensity. In
      addition, a set of medium-scale LNG spill tests were performed at the Brayton
      Fire Training Field to collect data for validating the ANSYS CFX prediction
      results. A comparison of test data with simulation results demonstrated that CFX
      was able to describe the dense gas behavior of LNG vapor cloud, and its
      prediction results of downwind gas concentrations close to ground level were in
      approximate agreement with the test data.

PMID- 20692093
TI  - Combined effects of sugarcane bagasse extract and synthetic dyes on the growth
      and bioaccumulation properties of Pichia fermentans MTCC 189.
AB  - Bioaccumulation of synthetic dyes viz. Acid Blue 93, Direct Red 28 and Basic
      Violet 3 by growing cells of yeast, Pichia fermentans MTCC 189 was investigated
      in growth media prepared from sugarcane bagasse extract. The maximum dye
      bioaccumulation was determined at pH 5.0 for all the dyes tested. Two kinetic
      models viz. Noncompetitive and Uncompetitive models were tested in order to
      determine the toxic effects of dyes on the specific growth rate of P. fermentans
      MTCC 189. Basic Violet 3 was found to be more toxic than the other two dyes. The
      combined effects of sugarcane bagasse extract and initial Basic Violet 3 dye
      concentrations on the specific growth rate and dye bioaccumulation efficiency of
      P. fermentans MTCC 189 was investigated and optimized using Response Surface
      Methodology (RSM). A 2(2) full factorial central composite design was
      successfully used for analysis of results. The optimum combination predicted via
      RSM confirmed that P. fermentans MTCC 189 was capable of bioaccumulating Basic
      Violet 3 dye upto 69.8% in the medium containing 10 mg/L of dye and 24 g/L sugar
      extracted from sugarcane bagasse.

PMID- 20692094
TI  - Complexation properties and synthesis of a novel Schiff base with triphenylene
      nucleus.
AB  - We presented the synthesis of a novel Schiff base and its complexation properties
      with some transition metal ions in this work. For this, the 2,3,4,6,7,10,11
      hexahydroxytriphenylene (HHTP) as starting material was synthesized according to
      known procedure. Moreover, the 2-((2-chloroethylimino)methyl) phenol material was
      prepared with reaction of salicylaldehyde and 2-chloroethylamine hydrochloride.
      To give the 2,3,4,6,7,10,11-hexakis(salicyliminoethoxy)triphenylene (HSE-TP) as a
      novel Schiff base, the HHTP were treated with 2-((2
      chloroethylimino)methyl)phenol in acetone media. Complexation properties of this
      Schiff base were investigated towards Ni(II), Cu(II), Co(II), Zn(II), Pd(II) and
      Cd(II) as transition metals. The structures of these new compounds (ligand and
      complexes) were characterized with FT-IR, magnetic susceptibility measurement,
      thermal methods (TGA), (1)H NMR and elemental analyses.

PMID- 20692095
TI  - Comparison of the removal of ethanethiol in twin-biotrickling filters inoculated
      with strain RG-1 and B350 mixed microorganisms.
AB  - This study aims to compare the biological degradation performance of ethanethiol
      using strain RG-1 and B350 commercial mixed microorganisms, which were inoculated
      and immobilized on ceramic particles in twin-biotrickling filter columns. The
      parameters affecting the removal efficiency, such as empty bed residence time
      (EBRT) and inlet concentration, were investigated in detail. When EBRT ranged
      from 332 to 66 s at a fixed inlet concentration of 1.05 mg L(-1), the total
      removal efficiencies for RG-1 and B350 both decreased from 100% to 70.90% and
      47.20%, respectively. The maximum elimination capacities for RG-1 and B350 were
      38.36 (removal efficiency=89.20%) and 25.82 g m(-3) h(-1) (removal
      efficiency=57.10%), respectively, at an EBRT of 83 s. The variation of the inlet
      concentration at a fixed EBRT of 110 s did not change the removal efficiencies
      which remained at 100% for RG-1 and B350 at concentrations of less than 1.05 and
      0.64 mg L(-1), respectively. The maximum elimination capacities were 39.93
      (removal efficiency=60.30%) and 30.34 g m(-3) h(-1) (removal efficiency=46.20%)
      for RG-1 and B350, respectively, at an inlet concentration of 2.03 mg L(-1).
      Sulfate was the main metabolic product of sulfur in ethanethiol. Based the
      results, strain RG-1 would be a better choice than strain B350 for the
      biodegradation of ethanethiol.

PMID- 20692096
TI  - Characteristics and personal exposures of carbonyl compounds in the subway
      stations and in-subway trains of Shanghai, China.
AB  - Carbonyl compounds including their concentrations, potential sources, diurnal
      variations and personal exposure were investigated in six subway stations and in
      subway trains in Shanghai in June 2008. The carbonyls were collected onto solid
      sorbent (Tenax TA) coated with pentafluorophenyl hydrazine (PFPH), followed by
      solvent extraction and gas chromatography (GC)/mass spectrometry (MS) analysis of
      the PFPH derivatives. The total carbonyl concentrations of in-subway train were
      about 1.4-2.5 times lower than in-subway stations. A significant correlation
      (R>0.5, p<0.01) between the concentrations of the low molecular-weight carbonyl
      compounds (<C(5)) and ozone was found in the subway stations. The diurnal
      variations in both the subway station and in-subway train showed that the
      concentrations of most carbonyls were much higher in the morning rush hour than
      in other sampling periods. Additionally, pronounced diurnal variations of
      acetaldehyde concentration before and after the evening peak hour in the subway
      train suggested that passengers contributed to high acetaldehyde levels. The
      personal exposure showed that the underground subway stations were important
      microenvironment for exposure to formaldehyde and acetaldehyde.

PMID- 20692097
TI  - Do sex differences exist in opioid analgesia? A systematic review and meta
      analysis of human experimental and clinical studies.
AB  - Although a contribution of sex in opioid efficacy has garnered much attention,
      the confirmation and direction of any such difference remain elusive. We
      performed a systematic review of the available literature on sex differences in
      MU and mixed MU/kappa opioid effect on acute and experimental pain. Fifty unique
      studies (including three unpublished studies) were included in the analyses.
      Across the 25 clinical studies on MU-opioids there was no significant sex
      analgesia association. Restricting the analysis to patient-controlled analgesia
      (PCA) studies (irrespective of the opioid) yielded greater analgesia in women
      (n=15, effect size 0.22, 95% c.i. 0.02-0.42, P=0.028). Further restricting the
      analysis to PCA morphine studies yielded an even greater effect in women (n=11,
      effect size=0.36, 95% c.i. 0.17-0.56, P=0.003). Meta-regression indicated that
      the longer the duration of PCA, the difference in effect between the sexes
      further increased. Across experimental pain studies on MU-opioids women had
      greater antinociception from opioids (n=11, effect size=0.35; 95% c.i. 0.01-0.69,
      P=0.047), which was predominantly due to 6 morphine studies. Female patients had
      greater MU/kappa opioid analgesia (n=7, effect size 0.84; 95% c.i. 0.25-1.43,
      P=0.005), but no sex-analgesia association was present in experimental studies
      (n=7). Sex differences exist in morphine-induced analgesia in both experimental
      pain studies and clinical PCA studies, with greater morphine efficacy in women.
      The data on non-morphine MU and mixed MU/kappa-opioids are less convincing and
      require further study.

PMID- 20692098
TI  - Reassessment of neuropathic pain in light of its revised definition: possible
      implications and consequences.

PMID- 20692099
TI  - Double aberration correction in a low-energy electron microscope.
AB  - The lateral resolution of a surface sensitive low-energy electron microscope
      (LEEM) has been improved below 4 nm for the first time. This breakthrough has
      only been possible by simultaneously correcting the unavoidable spherical and
      chromatic aberrations of the lens system. We present an experimental criterion to
      quantify the aberration correction and to optimize the electron optical system.
      The obtained lateral resolution of 2.6 nm in LEEM enables the first surface
      sensitive, electron microscopic observation of the herringbone reconstruction on
      the Au(111) surface.

PMID- 20692100
TI  - Reciprocal and real space maps for EMCD experiments.
AB  - Electron magnetic chiral dichroism (EMCD) is an emerging tool for quantitative
      measurements of magnetic properties using the transmission electron microscope
      (TEM), with the possibility of nanometer resolution. The geometrical conditions,
      data treatment and electron gun settings are found to influence the EMCD signal.
      In this article, particular care is taken to obtain a reliable quantitative
      measurement of the ratio of orbital to spin magnetic moment using energy filtered
      diffraction patterns. For this purpose, we describe a method for data treatment,
      normalization and selection of mirror axis. The experimental results are
      supported by theoretical simulations based on dynamical diffraction and density
      functional theory. Special settings of the electron gun, so called telefocus
      mode, enable a higher intensity of the electron beam, as well as a reduction of
      the influence from artifacts on the signal. Using these settings, we demonstrate
      the principle of acquiring real space maps of the EMCD signal. This enables
      advanced characterization of magnetic materials with superior spatial resolution.

PMID- 20692101
TI  - Responses of serum neurotrophic factors to exercise in pregnant and postpartum
      women.
AB  - It was recently shown in humans that exercise affects the neurotrophic factors
      known to function as neurogenesis regulators. No data related to exercise and
      pregnancy, however, is yet available. Thus, we investigated the effects of acute
      exercise on pregnant women during late pregnancy and women postpartum, on the
      serum concentration of the brain-derived neurotrophic factor (BDNF), the insulin
      like growth factor 1 (IGF-1), the vascular endothelial growth factor (VEGF),
      prolactin (PRL) and cortisol (COR). Twenty women with uncomplicated pregnancies
      underwent a graded submaximal exercise test during pregnancy (weeks 32-36 of
      gestation; T(1)) and postpartum (10-12 weeks after childbirth; T(2)). On two of
      these test days the women carried out an intensifying exercise test (25 W steps)
      on a cycle ergometer until a heart rate of 150 bpm was reached. Blood samples
      were taken in the rest period before beginning the exercise, immediately at the
      end of the exercise and after recovery periods of 5 and 10 min, respectively.
      Basal maternal IGF-1, PRL and COR were found to be higher during T(1) (p<.01),
      while the BDNF was higher during T(2) (p=.00). VEGF was not detectable in the
      serum of the pregnant women. During T(2), VEGF, which was found to be within the
      normal range before exercise, was at a higher level after exercise (p<.01).
      Exercise increased the BDNF and IGF-1 during T(1) and T(2) (p<.01). This study
      also shows that exercise increases the serum concentrations of IGF-1 and BDNF
      during pregnancy and postpartum as well as VEGF postpartum. Thus, exercise might
      be a beneficial lifestyle factor with therapeutic/public health implications i.e.
      with regard to maternal mood and cognitive performance.

PMID- 20692102
TI  - Social isolation and depressed mood are associated with elevated serum leptin
      levels in men but not in women.
AB  - BACKGROUND: Leptin, involved in energy homeostasis and a predictor of
      cardiovascular disease, has recently been recognized as mediator in stress
      reactions. We aimed to explore the association between leptin levels and two
      stress-related conditions, social isolation and depressed mood, both associated
      with increased cardiovascular mortality. METHODS: We analysed leptin levels in
      1229 subjects (643 men, 586 women), derived from the population-based MONIKA/KORA
      study. Standardized questionnaires were used to assess depressive mood and social
      isolation. In a multiple linear regression adjusted for body weight, age and
      survey, the association between leptin, social isolation and depressed mood and
      its interaction was explored in men and women separately. Leptin was then
      dichotomized and four analyses, adjusted for age, BMI, lifestyle factors,
      psychosomatic complaints and metabolic variables were performed to compare the
      risk of elevated leptin levels in the risk groups. RESULTS: Increased leptin
      levels were associated with social isolation (p=0.04) and the interaction between
      social isolation and depressed mood (p=0.02) in men but not in women. In socially
      isolated and depressed men, leptin levels (mean: 6.07 ng/ml) were significantly
      increased compared to neither depressed nor isolated men (mean: 4.51 ng/ml,
      p=0.04). In the multivariate adjusted logistic regression model, the combination
      of depressed state and social isolation was associated with a 4-fold increased
      risk (p<0.001) for elevated leptin levels. CONCLUSION: The finding of elevated
      leptin levels in socially isolated and depressed men raises the possibility that
      increased cardiovascular mortality in socially isolated men is partially mediated
      by hyperleptinemia.

PMID- 20692104
TI  - Does stress alter everyday moral decision-making?
AB  - Recent studies in the field of neuropsychological decision-making as well as
      moral psychology emphasize the role of emotions in decision-making. The current
      study examines whether stress affects moral decision-making. We induced stress in
      20 participants with the Trier Social Stress Test (TSST) and also examined 20
      participants in a control condition (Placebo TSST). The level of stress was
      assessed with questionnaires and endocrine markers (salivary cortisol and alpha
      amylase). All participants performed a moral decision-making task in which
      everyday moral dilemmas were described. Dilemmas varied in emotional intensity
      and each offered a rather egoistic and a rather altruistic option. Results show
      that groups did not differ significantly in everyday moral decision-making.
      However, cortisol responses and egoistic decision-making in emotional dilemmas
      were positively correlated. Our results indicate that stress per se does not
      cause more egoistic decision-making in the current setting but suggest an
      association between the individual's cortisol stress response and egoistic
      decision-making in high-emotional situations.

PMID- 20692103
TI  - Early-life stress, corticotropin-releasing factor, and serotonin transporter
      gene: a pilot study.
AB  - Recent studies have indicated a gene-by-environment interaction between serotonin
      transporter gene (5-HTTLPR) polymorphism and childhood abuse on depressive
      symptoms. In addition, persistent elevation of cerebrospinal fluid (CSF)
      corticotropin-releasing factor (CRF) concentrations following early-life
      adversity has been posited to underlie the subsequent development of major
      depression. This pilot study tested the hypothesis that elevations of juvenile
      CSF CRF concentrations are, in part, determined by an interaction between
      polymorphisms of the 5-HTTLPR and early-life stress. Nine juvenile male bonnet
      macaques (Macaca radiata) had been raised under variable foraging demand (VFD)
      conditions, a nonhuman primate model of early-life stress, whereas nine subjects
      were normatively raised under LFD (low foraging demand) conditions. Genotyping
      revealed that four (44.4%) of the VFD-reared monkeys possessed at least one "s"
      allele whereas five VFD monkeys were of the l/l genotype. Of the nine LFD
      subjects, two (22%) had the s/l genotype and seven had the l/l genotype. A
      "juvenile" CSF sample was obtained at approximately 3 years of age. CSF CRF
      concentrations were elevated specifically in the VFD "s/s" and "s/l" allele group
      in comparison to each of the remaining three groups, indicating a gene-by
      environment (G*E) interaction.

PMID- 20692105
TI  - Vestibular migraine may be an important cause of dizziness/vertigo in
      perimenopausal period.
AB  - Migraine disorders are more prevalent among women than men. The ovarian
      neurosteroids play an important role in this sex difference by modulating
      neurotransmitter systems involving migraine pathogenesis. During perimenopause,
      unlike the postmenopausal period, women are under unstable fluctuations of
      ovarian neurosteroid levels. Such fluctuations might be an important interval
      specific trigger for activating migraines. Along with migraine headache,
      dizziness is one of the most common complaints of perimenopause. A significant
      portion of this dizziness may be caused by vestibular migraine that has
      heterogeneous clinical features with dizziness and/or migraine headache. Because
      of this variation in phenomenology, the symptom of dizziness and vertigo during
      perimenopause is frequently misclassified as being a nonspecific climacteric
      symptom or having psychological origin. The recognition of vestibular migraine
      and its heterogeneous clinical presentations are important to understand,
      differentiate and correctly diagnose the symptom of dizziness and vertigo during
      perimenopausal transition. Further, recognition of the steroid influences on
      migraine genesis will lead to improved treatment regimens for vertigo from
      migraine.

PMID- 20692106
TI  - Using mirror visual feedback and virtual reality to treat fibromyalgia.
AB  - Fibromyalgia is a condition characterized by long term body-wide pain and tender
      points in joints, muscles and soft tissues. Other symptoms include chronic
      fatigue, morning stiffness, and depression. It is well known that these symptoms
      are exacerbated under periods of high stress. When pain becomes severe enough,
      the mind can enter what is known as a dissociative state, characterized by
      depersonalization - the feeling of detachment from one's physical body and the
      illusion of watching one's physical body from outside. In evolutionary terms,
      dissociative states are thought to be an adaptive mechanism to mentally distance
      oneself from pain, often during trauma. Similar dissociative experiences are
      reported by subjects who have used psychoactive drugs such as ketamine. We have
      previously used non-invasive mirror visual feedback to treat subjects with
      chronic pain from phantom limbs and suggested its use for complex regional pain
      syndrome: once considered intractable pain. We wondered whether such methods
      would work to alleviate the chronic pain of fibromyalgia. We tested mirror visual
      feedback on one fibromyalgia patient. On 15 trials, the patient's lower limb pain
      rating (on a scale from 1 to 10) decreased significantly. These preliminary
      results suggest that non-invasive dissociative anesthetics such as VR goggles,
      ketamine, and mirror visual feedback could be used to alleviate chronic pain from
      fibromyalgia. This would furnish us with a better understanding of the mechanism
      by which external visual feedback interacts with the internal physical
      manifestation of pain.

PMID- 20692107
TI  - Tenderness enhancement of beef from Bos indicus and Bos taurus cattle following
      electrical stimulation.
AB  - High voltage electrical stimulation (1130 V peak, 14.28 bidirectional half
      sinusoidal pulses/s) or low voltage stimulation (45 V peak, 36 alternating square
      wave pulses/s) was used on cattle: (1) low voltage stimulation applied for 10 or
      40 s with fast and slow chilling or high voltage stimulation for 60 s with normal
      chilling, applied to 100% Bos taurus cattle, (2) low voltage stimulation (40 s)
      and high voltage stimulation (60 s) with normal chilling applied to mixed Bos
      indicus and B.taurus cattle, (3) high voltage stimulation (54 s) with normal
      chilling applied to B. taurus and B. indicus cattle of 0-100% B. indicus
      composition, and (4) high voltage stimulation (60 s) applied to 100% B. taurus
      and 100% B. indicus cattle. All stimulation parameters enhanced the tenderness of
      steaks from M. longissimus thoracis et lumborum (LTL) aged at 1 degrees C up to
      28 days compared with non stimulated LTL. Short low voltage stimulation of 10s
      was marginally more effective than no stimulation and longer durations of 40s
      were very effective and high voltage stimulation was most effective. The shear
      force values for non stimulated B. indicus LTL are much greater than for B.
      taurus, but following high voltage stimulation LTL of B. indicus were similar to
      B. taurus and all had lower shear force values than from non stimulated
      carcasses. Thus adequate electrical stimulation removes any toughness of LTL
      related to B. indicus genetic composition.

PMID- 20692108
TI  - Effect of weaning status on animal performance and meat quality of Rubia Gallega
      calves.
AB  - The effect of weaning calves at different ages (NW=not weaned, W5=5.5 months old
      and W2=weaned after being born and then fed with natural Holstein Friesian milk
      until 2 months old), on animal performance and carcass and Longissimus thoracis
      muscle quality, was studied in 36 eight month-old Rubia Gallega calves. Feed
      ingestions, weight gains, slaughter (SW) and carcass weights (CW), carcass
      conformation and fat scores, and meat characteristics (24 hours postmortem):
      colour, pH, water holding capacity, chemical composition and texture (Warner
      Bratzler (WB) test, sensory panel), were studied. NW calves showed the highest SW
      and CW (P<0.001). Yellowness (b*), redness (a*) and chroma (C*) were higher in NW
      than W2 calves (P<0.05). Shear firmness was higher in W2 than in NW and W5 veal.
      W2 veal was less elastic (P<0.05), tender (P<0.05) and juicy (P<0.01) than NW and
      W5 veal.

PMID- 20692110
TI  - [The concept of characterized malpractice in wrongful birth].
AB  - OBJECTIVES: The law of March2002 was introducing a new concept of liability in
      the field of prenatal diagnosis, survey and investigations. For wrongful birth,
      medical physicians are responsible for newborn infants with congenital or
      hereditary disorder only in a case of characterized malpractices. MATERIALS AND
      METHODS: We performed a study about decisions that awarded or refused monetary
      damages specifically to the parents in the light of this new law. This research
      was performed by using official court rulings website, crossed in the search
      engine two expression-keys that were characterized: fault and antenatal
      diagnosis. Fifteen rulings were reviewed and studied. The matter of our research
      is to understand how the judges characterize the medical malpractice and insist
      upon the qualification "Blatant" in the field of prenatal medical liability?
      RESULTS: In fact, judicial decisions explicit more what it is not a characterized
      fault than what it is. Such judicial rejections stated that the medical practices
      were based on to established medical references and so couldn't be characterized.
      The taking care, the survey and the biological and radiological investigations of
      the pregnancy were evaluated in accordance to the knowledge of science although
      they didn't diagnose fetal malformations. Only four rulings accepted this kind of
      medical fault, focused the notion of medical neglect accompanied with hurriedness
      for some judges when physicians performed in particular antenatal echography. In
      these circumstances, the physician performed quickly and without interest the
      medical investigations which missed to detect fetal malformations. Two rulings of
      them categorized the malpractice by the inversion of results, and by the no
      information about unusual margin of error for cellular culture. The judge argued
      that negligence of health-care-providers denied to the parents the psychological
      preparation of hosting disabilities newborn. In this point of view, the judges
      want to damage parent's injuries.

PMID- 20692111
TI  - [Fetal hepatosplenomegaly in the third trimester: A sign of leukemia in fetuses
      with Down syndrome].
AB  - Risk for leukemic conditions increases in individuals with Down syndrome. We
      report a third trimester antenatal diagnosis of leukemia in a Down syndrome
      fetus. The third trimester ultrasound examination revealed a hepatosplenomegaly,
      which may suggest a myelopoiesis disorder. A review of the literature of eight
      cases described antenatally and 14 cases in the immediate neonatal period is
      presented.

PMID- 20692112
TI  - [An unexpected aetiology of massive haemoperitoneum during pregnancy].
AB  - We report the case of a 28-year-old woman who was diagnosed with massive
      hemoperitoneum while being 28 weeks pregnant. This para one woman had no previous
      history of endometriosis. During emergency caesarean section, she was diagnosed
      with superficial uterine rupture due to the spontaneous tearing of a sigmoid
      colon endometriotic lesion that was adherent to the posterior wall of the uterus.
      Endometriotic lesion is an exceptional aetiology of spontaneous hemoperitoneum
      during pregnancy and is usually due to the rupture of uterine vessel. To our
      knowledge, spontaneous rupture of a colon lesion adherent to the posterior
      surface of the uterus has not yet been reported.

PMID- 20692113
TI  - [Cervical disease in postmenopausal HIV-1-infected women].
AB  - INTRODUCTION: An increasing number of HIV-1-infected women reaches the age of
      menopause. This infection is associated with a higher incidence of cervical
      squamous intraepithelial lesions (low-grade or LSIL, high grade or HSIL). The aim
      of our study was to describe the cervical disease in these patients during
      menopause. PATIENTS AND METHODS: Retrospective study, identifying all Pap smears
      and colposcopy in HIV-1-infected postmenopausal women between 1995 and 2008, in
      our hospital. RESULTS: Eighteen postmenopausal women, aged of 54 years (43-63),
      have HIV-1 infection since 7.5 years (2-25). Fifty-one pathological exams were
      reviewed in which 27 (50.98%) abnormal, including four (7.84%) ASC-US, 15
      (29.41%) LSIL lesions, and seven (13.73%) HSIL. Ten patients had surgery (laser,
      conisation, hysterectomy) during the period. The evolution of cervical lesions
      was: stability in 40.48%, regression in 35.71% and progression in 23.81%. The
      median time to develop an HSIL at menopause was 5 years. CONCLUSION: In our
      study, postmenopausal HIV-1-infected women have most frequently LSIL and
      persistent. Monitoring of these postmenopausal women should be continued, the
      attitude to realise an initial HPV typing and confirmation of an abnormal
      annually Pap smear with colposcopic exam should be confirmed by larger study.

PMID- 20692114
TI  - Body reserves and ovarian performance in primiparous lactating rabbit does
      submitted to early weaning as a strategy to decrease energy deficit.
AB  - The aim of this work was to study the effect on body composition, serum metabolic
      parameters and ovarian status of early weaning at 25 Days post-partum (dpp) as a
      strategy to decrease energy deficit of primiparous lactating rabbit does prior to
      insemination at 32 dpp following an extensive rhythm. A total of 34 primiparous
      lactating rabbit does were used and distributed in three groups: 10 lactating
      does euthanized at 25 dpp (group L25), 13 does weaned at 25 dpp and euthanized at
      32 dpp (group NL32), and 11 non weaned lactating does euthanized at 32 dpp (group
      L32). No significant differences were observed in live body weight, ovary weight,
      serum NEFA and total protein concentration among groups. Although NL32 does had a
      low feed intake (122+/-23.5g/Day; P<0.001), their estimated lipids (16.9+/-1.09%,
      P<0.008), protein (19.7+/-0.07%, P<0.0001), and energy (1147+/-42.7MJ/kg,
      P<0.006) body contents were higher and their serum glucose concentrations (158+/
      24.5mg/dl, P<0.04) were lower compared to L25 does (11.9+/-1.3%, 18.5+/-0.08%,
      942+/-51.3MJ/kg and 212+/-27.9mg/dl) and L32 does (13.4+/-1.03%, 18.5+/-0.1%,
      993+/-40.4MJ/kg and 259+/-29.5mg/dl), respectively. In the ovarian surface of L25
      does a lower number of follicles > or =1mm was observed compared to NL32 and L32
      groups (12.7+/-1.5 vs. 18.0+/-1.45 and 17.6 +/-1.67; P<0.05). Follicular
      population in the histological ovarian sections and immunolocalization of
      prolactin receptor were similar between groups. In group L25, both nuclear
      maturation of oocytes in terms of Metaphase II rate (67.0 vs. 79.7 and 78.3%;
      P<0.05) and cytoplasmic maturation measured by percentage of cortical granules
      (CG) totally or partially migrated in oocytes were significantly lower than in
      groups NL32 and L32 (16.0 vs. 38.3 and 60.0%; P<0.05). Consequently, a higher
      rate of oocytes with non-migrated CGs was found in group L25 than in groups NL32
      and L32 (76.0 vs. 46.8 and 33.3%; P<0.05). In conclusion, even though early
      weaning at 25 dpp seemed to improve body energy stores of primiparous does, this
      fact was not well reflected on the ovarian status at 32 dpp, which was similar
      regardless of weaning time and it could be performed later.

PMID- 20692115
TI  - Relationship of spermatoscopy, prostatic acid phosphatase activity and prostate
      specific antigen (p30) assays with further DNA typing in forensic samples from
      rape cases.
AB  - In the forensic laboratory the biological analyses for rape investigation
      commonly include vaginal swabs as sample material combined to biochemical tests
      including sperm cytology (SC) and detection of acid phosphatase activity (AP) and
      prostate-specific antigen (PSA, p30) for the conclusive identification of semen
      components. Most reports comparing these tests relied on analysis of semen
      samples or donor swabs taken under controlled conditions; however their
      individual or combined efficacy under real live sampling conditions in different
      laboratories is largely unknown. We carried out SC, APA and PSA analyses in
      vaginal swabs collected from casework rapes submitted to Mexican Forensic
      Laboratories at Texcoco and Toluca. On the basis of positive and negative results
      from each assay and sample, data were classified into eight categories (I-VIII)
      and compared with those obtained in the two only similar studies reported in
      Toronto, Canada and Hong Kong, China. SC and APA assays had the higher overall
      positivity in Toluca and Texcoco samples respectively and otherwise PSA had a
      lower but very similar positivity between these two laboratories. When compared
      to the previous studies some similarities were found, namely similar frequencies
      (at a ratio of approximately 1 out of 3) of samples being positive or negative by
      all techniques (Categories I and VI respectively) and a comparable overall
      positivity of APA and SC but higher than that of PSA. Indeed the combined results
      of using SC, APA and PSA tests was considered as conclusive for semen detection
      from approximately 1 out of 3 cases (Category I) to approximately 1 out of 2
      cases in a scenario where at least SC is positive, strongly presumptive in 2 out
      of 3 cases (with at least one test positive) and the remainder 1 out of 3 cases
      (Category VI) suggested absence of semen. By determining Y-STR polymorphisms (12
      loci) in additional samples obtained at Toluca laboratory, complete DNA profiles
      were determined from all Category I samples, none marker was detected from all
      Category VI samples and mostly partial profiles were obtained from samples of
      other categories. These observations give an overview on the variability in
      efficacy of each test performed at different laboratories and provide a general
      notion about the in praxis contribution of SC, APA and PSA tests for further DNA
      typing in the forensic analysis of rape.

PMID- 20692116
TI  - Radiologically placed tunneled peritoneal catheter in palliation of malignant
      ascites.
AB  - The purpose of this study was to evaluate retrospectively the safety and
      effectiveness of radiologically placed tunneled peritoneal catheter in palliation
      of malignant ascites. Between July 2005 and June 2009, 41 tunneled peritoneal
      catheters were placed under ultrasonographic and fluoroscopic guidance in 40
      patients (mean age, 55 years; 22 women) who had symptomatic malignant ascites. No
      procedure related mortality was observed. Major complication occurred in one
      patient (2.5%) in the form of serious bacterial peritonitis that necessitated
      catheter removal. Minor complications such as minor bacterial peritonitis,
      catheter dislodgement, tunnel infection, and catheter blockage occurred in 11
      patients (27.5%). The mean duration of survival after catheter placement was 11.8
      weeks. All patients expired of their primary malignancies in the follow-up.
      Radiologically placed tunneled peritoneal catheter is safe and effective in
      palliation of symptomatic malignant ascites.

PMID- 20692117
TI  - In vitro assay of the interaction between Rnc1 protein and Pmp1 mRNA by affinity
      capillary electrophoresis with a carboxylated capillary.
AB  - The interaction between Rnc1, an RNA interactive protein, and a Pmp1 mRNA was
      investigated by affinity capillary electrophoresis (ACE). Prior to the ACE
      experiments, the column performances of three capillaries (an untreated fused
      silica capillary, a polybrene-polyacrylic acid (PB-PAA) double layer coating
      capillary, and a carboxylated capillary with a covalent modification) were
      studied with model proteins including ribonuclease B (RNase B) and bovine serum
      albumin (BSA). Using an untreated fused silica and a PB-PAA double layer coating
      capillaries, both of the protein peaks were broad and tailing. However, using a
      carboxylated capillary, the protein peaks were sharp and symmetric, and migration
      times were repeatable (RSD<0.4%). Further, the proteins in human serum also gave
      sharp peaks and its repeatability was kept at a high level by pre-treatment of a
      capillary inner wall with 1M sodium chloride solution before each run. An Rnc1
      protein was analyzed by ACE with background electrolytes containing various
      concentrations of Pmp1 sense mRNA using a carboxylated capillary. Increase in the
      concentration of the mRNA was found to delay the migration time of the protein.
      But the migration time of the protein was kept constant with increasing Pmp1 anti
      sense mRNA instead of Pmp1 sense mRNA. A straight line (r=0.987) was obtained by
      plotting 1/(migration time shift) versus 1/(Pmp1 sense mRNA concentration) and
      the association constant of Rnc1 protein with Pmp1 sense mRNA could be estimated
      to be 4.15x10(6)M(-1). These results suggest that the association constants of
      proteins with mRNAs as ligands were easily determined by the proposed method.

PMID- 20692118
TI  - Patients' reaction to the disclosure of rare dreaded adverse events.
AB  - BACKGROUND: Physicians must frequently inform their patients of the risks of
      rare, but serious, adverse events (AEs). OBJECTIVE: To examine how patients react
      to the disclosure of rare AEs. METHODS: Outpatients viewed a video of a physician
      describing a medication associated with a rare AE. Subjects then rated their
      worry, perceived chance of developing the AE, and willingness to take the
      medication. RESULTS: Non-White men were more likely to perceive a greater chance
      of developing the AE compared to White men [Adjusted odds ratio (95% CI) = 3.37
      (1.09-10.45)]; White women were more likely to be worried [2.00 (0.95-4.24)] and
      to perceive a greater chance of developing the [6.22 (2.50-15.50)], perceive a
      greater chance of developing the AE [6.27 (2.43-16.15)], and be less willing to
      take the medication [0.23 (0.09-0.59)], compared to White men. CONCLUSIONS:
      Gender and ethnicity influence how patients react to disclosure of rare, but
      serious, AEs. PRACTICE IMPLICATIONS: An improved understanding of patients' risk
      perceptions is required to inform the development of best practices to improve
      risk communication.

PMID- 20692119
TI  - Arthroscopic rotator cuff repair with metal and biodegradable suture anchors: a
      prospective randomized study.
AB  - PURPOSE: The purpose of this study was to compare the clinical outcome of
      arthroscopic rotator cuff repair with metal and biodegradable suture anchors.
      METHODS: Arthroscopic rotator cuff repair was performed in 110 patients with a
      full-thickness rotator cuff tear. They were divided into 2 groups of 55 patients
      each, according to suture anchors used: metal anchors in group 1 and
      biodegradable anchors in group 2. Results were evaluated by use of the
      Disabilities of the Arm, Shoulder and Hand (DASH) and Work-DASH self-administered
      questionnaires, as well as the Constant score normalized for age and sex. On
      analyzing the results at 2 years' follow-up, we considered the following
      independent variables: baseline scores; age; sex; arm dominance; location, shape,
      and retraction of cuff tear; fatty degeneration; treatment of biceps tendon;
      rotator cuff repair technique (anchors or anchors and side to side); and number
      of anchors. Univariate and multivariate statistical analyses were performed to
      determine which variables were independently associated with the outcome.
      Significance was set at P < .05. RESULTS: Of the patients, 9 (8.2%) were lost to
      follow-up. Comparison between groups did not show significant differences for
      each variable considered. Overall, according to the results, the mean DASH scores
      were 17.6 +/- 17.2 points in group 1 and 22.8 +/- 19.9 points in group 2; the
      mean Work-DASH scores were 24.9 +/- 28.1 points and 22.5 +/- 24.1 points,
      respectively; and the mean Constant scores were 104 +/- 20.5 points and 98.6 +/-
      14.3 points, respectively. Differences between groups 1 and 2 were not
      significant. Univariate and multivariate analysis showed that only baseline
      score, age, tear location, and fatty degeneration significantly and independently
      influenced the outcome. CONCLUSIONS: At a short-term follow-up, differences
      between arthroscopic repair of full-thickness rotator cuff tears with metal and
      biodegradable suture anchors were not significant. LEVEL OF EVIDENCE: Level I,
      high-quality randomized controlled trial with no statistically significant
      differences but narrow confidence intervals.

PMID- 20692120
TI  - Comparing stability of different single- and double-bundle anterior cruciate
      ligament reconstruction techniques: a cadaveric study using navigation.
AB  - PURPOSE: The objective of this study was to analyze 2 different single-bundle
      anterior cruciate ligament (ACL) reconstruction procedures and compare their
      ability to reduce the pivot-shift phenomenon with an anatomic double-bundle (DB)
      technique. METHODS: Twelve fresh-frozen cadaveric hip-to-toe lower extremity
      specimens were used. ACL reconstructions were performed by conventional single
      bundle, anteromedial (AM) single-bundle, and DB techniques. Anterior tibial
      translation was measured in the intact knee, ACL-deficient knee, and the 3 ACL
      reconstructions in response to a Lachman test and a mechanized pivot-shift test.
      A surgical navigation system (Praxim Medivision, Grenoble, France) simultaneously
      tracked kinematics. RESULTS: Intact knees were clinically graded as grade 0 (n =
      12). ACL-deficient knees were graded as grade 1 (n = 10) and grade 2 (n = 2).
      With a mechanized pivot-shift test, anterior tibial translation was 1.7 +/- 3.0
      mm, 9.7 +/- 3.8 mm, 4.4 +/- 1.0 mm, 1.8 +/- 1.5 mm, and -1.7 +/- 3.3 mm for
      intact knees, ACL-deficient knees, conventional technique, AM technique, and DB
      technique, respectively. There was a significant difference between the DB
      technique and both single-bundle techniques tested (P < .05). CONCLUSIONS: The
      model used represents an isolated ACL injury without concomitant injury to the
      capsuloligamentous restraints or menisci. However, during the pivot shift,
      neither type of single-bundle ACL reconstruction stabilized the knee to the same
      degree as the DB ACL reconstruction. CLINICAL RELEVANCE: In this cadaveric model
      a DB repair offers great anterior and rotational stability. Although this study
      suggests that the DB technique is biomechanically superior to a single-bundle
      technique using traditional transtibial tunnel positions, there appear to be
      minimal differences in knee kinematics during stability testing with the DB
      technique versus an AM graft position. Indeed, compared with the AM position
      alone, the DB technique "overconstrained" the kinematics of the knee during a
      pivoting maneuver at time zero in a cadaveric model with an isolated ACL injury.

PMID- 20692121
TI  - Reconstruction of hyperspectral cutaneous data from an artificial neural network
      based multispectral imaging system.
AB  - The development of an integrated MultiSpectral Imaging (MSI) system yielding
      hyperspectral cubes by means of artificial neural networks is described. The MSI
      system is based on a CCD camera, a rotating wheel bearing a set of seven
      interference filters, a light source and a computer. The resulting device has
      been elaborated for in vivo imaging of skin lesions. It provides multispectral
      images and is coupled with a software reconstructing hyperspectral cubes from
      multispectral images. Reconstruction is performed by a neural network-based
      algorithm using heteroassociative memories. The resulting hyperspectral cube
      provides skin optical reflectance spectral data combined with bidimensional
      spatial information. This combined information will hopefully improve diagnosis
      and follow-up in a range of skin disorders from skin cancer to inflammatory
      diseases.

PMID- 20692122
TI  - Development of the International Classification of Functioning, Disability and
      Health as a brief head and neck cancer patient questionnaire.
AB  - WHO has adopted the International Classification of Functioning, Disability and
      Health (ICF) to assess functioning and disability. A Brief ICF Core Set for head
      and neck cancer comprises 19 items. This study developed a patient self-completed
      questionnaire from the items of the brief core set (BCSQ-H&N), compared the BCSQ
      H&N questionnaire with the University of Washington v.4 (UW-QOLv4) and compared
      the BCSQ-H&N results with a clinician-rated evaluation. UW-QOL v4 and BCSQ-H&N
      were sent to 751 disease-free head and neck cancer patients in April 2008. 376
      patients responded to the questionnaire and 25 were interviewed. The percentage
      reporting significant problems in BCSQ-H&N items ranged between 11% and 43%. The
      type of problem varied with tumour site. Patients with smaller tumours and
      patients without radiotherapy reported better outcomes. The BCSQ-H&N correlated
      well with appropriate items in the UW-QOLv4 especially for functional outcome.
      There were systematic differences between observer-rated scores and patient self
      completed questionnaire responses. Patients suggested additional items for
      inclusion, namely taste, jaw opening, articulation function, structure of
      shoulder region, loss of function at the free flap donor site, and intimate
      relationships. Further validation is required but BCSQ-H&N shows promise as an
      outcome measure for global use.

PMID- 20692123
TI  - Additive interactions of pregabalin with lamotrigine, oxcarbazepine and
      topiramate in the mouse maximal electroshock-induced seizure model: a type I
      isobolographic analysis for non-parallel dose-response relationship curves.
AB  - The aim of this study was to characterize the anticonvulsant effects of
      pregabalin (PGB-a third-generation antiepileptic drug) in combination with three
      second-generation antiepileptic drugs (i.e., lamotrigine [LTG], oxcarbazepine
      [OXC] and topiramate [TPM]) in the mouse maximal electroshock (MES)-induced
      seizure model by using the type I isobolographic analysis for non-parallel dose
      response relationship curves (DRRCs). Tonic hind limb extension (seizure
      activity) was evoked in adult male albino Swiss mice by a current (sine-wave,
      25mA, 500V, 50Hz, 0.2s stimulus duration) delivered via auricular electrodes.
      Potential adverse-effect profiles of interactions of PGB with LTG, OXC and TPM at
      the fixed-ratio of 1:1 in the MES test with respect to motor performance, long
      term memory and skeletal muscular strength were measured. In the mouse MES model,
      PGB administered singly had its DRRC non-parallel to that for LTG, OXC and TPM.
      With type I isobolography for non-parallel DRRCs, the combinations of PGB with
      LTG, OXC and TPM at the fixed-ratio of 1:1 exerted additive interaction. In all
      combinations, neither motor coordination, long-term memory nor muscular strength
      were affected. In conclusion, the additive interactions between PGB and LTG, OXC
      and TPM are worthy of consideration while extrapolating the results from this
      study to clinical settings.

PMID- 20692124
TI  - Aberrant EEG responses to gamma-frequency visual stimulation in schizophrenia.
AB  - Disturbance in the integration of visual information is one of the hallmarks of
      schizophrenia. In the spatial domain, visual integration is compromised,
      resulting in impaired perceptual grouping and contour integration. In the time
      domain, in contrast, visual integration is enhanced, as manifested by increased
      backward masking and lower ability of patients to detect successively presented
      visual stimuli as asynchronous. There is much evidence that integrative processes
      in the brain are supported by dynamic synchronization, or phase-locking, of
      neural firing. In particular, synchrony in the gamma band (>30 Hz) has been
      related to local visual information binding whereas synchrony in lower
      frequencies has been linked to global-scale integration. We recorded EEG signals
      evoked by steady-state gamma-frequency (40 Hz) photic stimulation in order to
      directly test the phase-locking of neural responses in schizophrenia. Compared
      with healthy control subjects, patients showed higher phase-locking of early
      evoked activity in the gamma band (36-44 Hz) over the posterior cortex, but lower
      phase-locking in theta (4-8 Hz), alpha (8-13 Hz) and beta (13-24 Hz) frequencies
      over the anterior cortex. Phase-locking of evoked responses separated
      schizophrenia and control subjects with accuracy of 86%. This result suggests
      that schizophrenia is associated with an enhanced early low-level integration in
      the visual cortex but a deficient high-level integration of visual information
      within the brain global workspace.

PMID- 20692125
TI  - Neuropsychological profiles in individuals at clinical high risk for psychosis:
      relationship to psychosis and intelligence.
AB  - BACKGROUND: Characterizing neuropsychological (NP) functioning of individuals at
      clinical high risk (CHR) for psychosis may be useful for prediction of psychosis
      and understanding functional outcome. The degree to which NP impairments are
      associated with general cognitive ability and/or later emergence of full
      psychosis in CHR samples requires study with well-matched controls. METHODS: We
      assessed NP functioning across eight cognitive domains in a sample of 73 CHR
      youth, 13 of whom developed psychotic-level symptoms after baseline assessment,
      and 34 healthy comparison (HC) subjects. Groups were matched on age, sex,
      ethnicity, handedness, subject and parent grade attainment, and median family
      income, and were comparable on WRAT-3 Reading, an estimate of premorbid IQ.
      Profile analysis was used to examine group differences and the role of IQ in
      profile shape. RESULTS: The CHR sample demonstrated a significant difference in
      overall magnitude of NP impairment but only a small and nearly significant
      difference in profile shape, primarily due to a large impairment in olfactory
      identification. Individuals who subsequently developed psychotic-level symptoms
      demonstrated large impairments in verbal IQ, verbal memory and olfactory
      identification comparable in magnitude to first episode samples. CONCLUSIONS: CHR
      status may be associated with moderate generalized cognitive impairments marked
      by some degree of selective impairment in olfaction and verbal memory.
      Impairments were greatest in those who later developed psychotic symptoms. Future
      study of olfaction in CHR samples may enhance early detection and specification
      of neurodevelopmental mechanisms of risk.

PMID- 20692126
TI  - An investigation of a possible relationship between olfactory identification
      deficits at first episode and four-year outcomes in patients with psychosis.
AB  - OBJECTIVE: Olfactory identification deficits are found in a significant
      proportion of patients with schizophrenia spectrum psychotic disorders and appear
      to be predictive of incomplete remission of negative and cognitive symptoms. In
      the current study, we examined whether patients with first episode psychosis who
      have olfactory identification deficits (microsmic) have poorer functional outcome
      than those whose olfactory status is normal (normosmic). METHOD: Sixty-six (66)
      first episode psychosis patients (46 M and 20 F) were assessed with the
      University of Pennsylvania Smell Identification Test (UPSIT) at baseline. UPSIT
      scores served to classify patients into subgroups. The patients' psychiatrists
      completed the Social and Occupational Functioning Assessment Scale (SOFAS) and
      the Levels of Functioning Scale (LOFS) after at least 6 months of treatment. The
      Premorbid Assessment Scale (PAS) was rated by a parent at baseline. RESULTS:
      Thirty-eight percent (38%) of the sample was identified as 'microsmic'. LOFS and
      SOFAS scores were significantly lower in the microsmic group than in the
      normosmic group. Symptoms were significantly worse in the microsmic group in
      comparison to the normosmic group. PAS scores did not differ between groups.
      CONCLUSIONS: First episode patients identified as microsmic at baseline
      assessment went on to demonstrate poorer functional outcome compared to normosmic
      patients despite no differences in premorbid adjustment. Olfactory identification
      deficits at first episode may provide a marker for poorer outcome. Testing
      olfaction is simple and inexpensive, and could provide clinically valuable
      information at first episode to identify those patients who might benefit from
      more intensive interventions promoting functional recovery.

PMID- 20692127
TI  - Update on brucellosis: therapeutic challenges.
AB  - Brucellosis is an extremely important disease around the world, especially in
      developing countries. Its clinical manifestations and severity vary with the
      patient population studied and the species of Brucella involved. The choice of
      regimen and duration of antimicrobial therapy should be based on whether focal
      disease is present or there are underlying conditions that contraindicate certain
      antibiotics (e.g. pregnant patients or children under 8 years old). Most
      individuals with acute brucellosis respond well to a combination of doxycycline
      plus aminoglycosides or rifampicin for 6 weeks. Monotherapy with doxycycline or
      minocycline, or a combination of doxycycline plus trimethoprim-sulfamethoxazole,
      or a quinolone plus rifampicin may be an alternative. Patients with focal
      disease, such as spondylitis or endocarditis, may require longer courses of
      antibiotics, depending on clinical evolution. Tetracycline monotherapy,
      especially with doxycycline, is a good option for patients with brucellosis with
      no focal lesions and a low risk of relapse. In this clinical situation,
      practitioners should avoid the use of high-cost or more toxic schedules.

PMID- 20692128
TI  - Update on laboratory diagnosis of human brucellosis.
AB  - The persistent worldwide prevalence of human brucellosis causes serious public
      health concerns and economic loss to communities. The multisystem involvement and
      the protean and unusual clinical presentations of the disease pose significant
      diagnostic challenges. The clinical features are non-specific and can overlap
      with a wide spectrum of other infectious and non-infectious diseases, leading to
      brucellosis being labelled the 'disease of mistakes'. Protracted chronicity and
      serious complications can result and mislead physicians onto a path of costly
      laboratory and radiological investigations. To reach a diagnosis clinicians must
      use a wide range of non-specific routine haematological and biochemical tests in
      addition to Brucella-specific assays. The latter are microbiological (culture),
      serological (e.g. slide or tube agglutination, Coombs test, immunocapture
      agglutination, Brucellacapt, immunochromatographic lateral flow, enzyme-linked
      immunosorbent assays and the indirect fluorescent antibody test) and molecular
      (e.g. polymerase chain reaction (PCR) and real-time PCR). Each of these tests has
      advantages and limitations, and thus requires careful interpretation. Since
      brucellosis can have several presentations and phases (acute, subacute, chronic,
      relapsed, active and inactive), the search for reliable, discriminatory
      diagnostic and prognostic markers, especially for monitoring disease evolution,
      are ongoing. Although much progress has been made, further challenges remain to
      the accurate diagnosis of this historic but still common global zoonotic disease.

PMID- 20692129
TI  - Synergistic effect of erythromycin on polymorphonuclear cell antibacterial
      activity against erythromycin-resistant phenotypes of Streptococcus pyogenes.
AB  - To evaluate the synergistic activity of erythromycin and human polymorphonuclear
      cells (PMNs) on the binomial erythromycin-resistant (ERY(R)) Streptococcus
      pyogenes/host, the phagocytic and bactericidal activities of PMNs against ERY(R)
      streptococcal strains (cMLS(B), M, and iMLS(B) A, B and C phenotypes) were
      assessed in the presence of the macrolide. The results showed that when
      erythromycin, PMNs and streptococci [both erythromycin-sensitive (ERY(S)) and
      ERY(R)] were simultaneously present in the culture medium, PMN phagocytic
      activity was similar to that of drug-free controls. In contrast, the results
      emphasised a significant high increase in intracellular killing by PMNs in the
      presence of erythromycin not only for ERY(S) streptococci but also for ERY(R)S.
      pyogenes with high (cMLS(B), iMLS(B) A and iMLS(B) B phenotypes) and moderate (M
      and iMLS(B) C phenotypes) erythromycin resistance compared with controls without
      drug. From literature data it emerged that, even if intracellularly concentrated,
      erythromycin is relatively inactive because of its instability. The results
      indicate that the enhanced intra-PMN streptococcal killing detected is mainly
      attributable to PMN bactericidal systems that synergise with intracellular
      erythromycin in eradicating ERY(R)S. pyogenes strains (both with high and
      moderate resistance). These data confirm that the antibiotic resistance detected
      in vitro does not always imply a failure of antimicrobial treatment.

PMID- 20692130
TI  - Characterisation and evaluation of synthetic antimicrobial peptides against
      Bacillus globigii, Bacillus anthracis and Burkholderia thailandensis.
AB  - Antimicrobial peptides (AMPs) are produced by all forms of living organisms and
      represent a novel class of antibiotics to treat infectious diseases. In this
      study, 29 AMPs of varying length and characteristics were synthesised chemically
      and were evaluated for their ability to inhibit the growth of Bacillus globigii,
      Bacillus anthracis and Burkholderia thailandensis. Amongst the peptides tested,
      sheep myeloid antimicrobial peptide-29 (SMAP-29) was the most potent, inhibiting
      both B. globigii and B. anthracis at submicromolar concentrations. However, SMAP
      29 was less effective against B. thailandensis (minimum inhibitory concentration
      of 71 microM). Haemolytic activity and cytotoxicity were determined using human
      blood cells and human embryonic kidney 293S cells, respectively. Most of the
      peptides tested showed varying degrees of haemolytic activity and cytotoxicity,
      with SMAP-29 being highly haemolytic and cytotoxic under the conditions tested.
      Nevertheless, strategies to reduce toxicity whilst maintaining high antimicrobial
      activity are worth pursuing in light of the results obtained.

PMID- 20692131
TI  - Genes differentially expressed in CB1 knockout mice: involvement in the
      depressive-like phenotype.
AB  - Recent hypotheses to explain the neurobiology of depression underline the role
      played by stress in mood disorders. The endocannabinoid system is one of the
      major physiological substrates involved in emotional responses and stress. Thus,
      mice lacking CB(1) receptor exhibit a depressive-like phenotype and an increased
      vulnerability to deleterious effects of stress. In order to identify possible
      molecular pathways contributing to this phenotype, we have examined the gene
      expression profile of mutants at basal conditions and after the exposure to
      repeated stress. Several genes coding for neurotransmitter receptors,
      neurotrophic factors, neuropeptides and hormones receptors were differentially
      expressed in CB(1) knockout mice.

PMID- 20692132
TI  - The relationship between the concentration of ganglioside GM1 and antitumor
      activity of edelfosine--the Langmuir monolayer study.
AB  - One of the characteristic features of tumor membranes is altered concentration of
      gangliosides level and their over-expression in tumor progression. This fact
      should be considered when the mechanism of activity and selectivity of edelfosine
      (ED)--a membrane-active anticancer drug--is investigated. Strong affinity of this
      drug to ganglioside GM1, found in binary mixed monolayers, encouraged us for a
      deeper investigations on more complex model systems. In this work we have studied
      the influence of edelfosine on the interactions between molecules in model
      sphingomyelin/cholesterol monolayer, mimicking a tumor membrane, containing
      ganglioside in increasing proportion that is characteristic of cancer
      progression. It was found that edelfosine in very low concentration (1%)
      practically does not influence on model membrane system, independently of the
      proportion of ganglioside. On the other hand, at the increased ED concentration
      (10%), the interactions between the lipids in the mixed system become
      progressively stronger upon the increase of ganglioside concentration as compared
      to those in the model tumor membrane. The results of our investigations show that
      the affinity of edelfosine towards tumor cells may be correlated with over
      expression of gangliosides in cancer cells.

PMID- 20692133
TI  - Milk whey proteins and xanthan gum interactions in solution and at the air-water
      interface: a rheokinetic study.
AB  - In this contribution, we present experimental information about the effect of
      xanthan gum (XG) on the adsorption behaviour of two milk whey protein samples
      (MWP), beta-lactoglobulin (beta-LG) and whey protein concentrate (WPC), at the
      air-water interface. The MWP concentration studied corresponded to the protein
      bulk concentration which is able to saturate the air-water interface (1.0 wt%).
      Temperature, pH and ionic strength of aqueous systems were kept constant at 20
      degrees C, pH 7 and 0.05 M, respectively, while the XG bulk concentration varied
      in the range 0.00-0.25 wt%. Biopolymer interactions in solution were analyzed by
      extrinsic fluorescence spectroscopy using 1-anilino-8-naphtalene sulphonic acid
      (ANS) as a protein fluorescence probe. Interfacial biopolymer interactions were
      evaluated by dynamic tensiometry and surface dilatational rheology. Adsorption
      behaviour was discussed from a rheokinetic point of view in terms of molecular
      diffusion, penetration and conformational rearrangement of adsorbed protein
      residues at the air-water interface. Differences in the interaction magnitude,
      both in solution and at the interface vicinity, and in the adsorption rheokinetic
      parameters were observed in MWP/XG mixed systems depending on the protein type
      (beta-LG or WPC) and biopolymer relative concentration. beta-LG adsorption in XG
      presence could be promoted by mechanisms based on biopolymer segregative
      interactions and thermodynamic incompatibility in the interface vicinity,
      resulting in better surface and viscoelastic properties. The same mechanism could
      be responsible of WPC interfacial adsorption in the presence of XG. The
      interfacial functionality of WPC was improved by the synergistic interactions
      with XG, although WPC chemical complexity might complicate the elucidation of
      molecular events that govern adsorption dynamics of WPC/XG mixed systems at the
      air-water interface.

PMID- 20692134
TI  - Coimmobilization of heparin/fibronectin mixture on titanium surfaces and their
      blood compatibility.
AB  - Coimmobilization as a versatile biomodification technique has been widely used in
      the development of biomimetic materials with superior mechanical and biological
      properties. In this study, a mixture of heparin and fibronectin (Hep/Fn) was
      tested for its hemocompatibility after either physisorption or covalent
      coimmobilization to a titanium (Ti) substrate. The process of substrate
      activation and film deposition was associated with an increase of roughness;
      successful immobilization in both cases was demonstrated by FTIR. The immobilized
      heparin amount was probed by toluidine blue O binding, fibronectin by
      immunochemistry. Both molecules had slightly higher concentrations on the
      physisorbed film than after covalent coimmobilization. Plasmatic coagulation
      activation, tested as activated partial thromboplastin time APTT, and platelet
      adhesion were significantly improved on the covalently coimmobilized samples than
      on the physisorbed or blank ones. All these results suggest that the covalent
      coimmobilization of heparin with fibronectin improved the anticoagulant activity
      of heparin and caused a favorable blood compatibility. We envisage that this
      method will provide a potential and effective selection for biomaterials surface
      modification.

PMID- 20692135
TI  - Tumour lysis syndrome after splenic irradiation in a patient with JAK2 V617F post
      polycythaemia vera myelofibrosis.

PMID- 20692136
TI  - Brachytherapy for cervix cancer: time for change.

PMID- 20692137
TI  - Genetic regulation of inflammation-mediated activation of haemostasis: family
      based approaches in population studies.
AB  - Blood coagulation and inflammation play a key role in atherosclerosis and
      thrombosis. Candidate gene and genome wide association studies have identified
      potential specific genes that might have a causal role in these pathogenic
      processes. The analysis of quantitative traits is more powerful as they are
      closer to direct gene action than disease phenotypes. Thus linkage-based studies
      on extended families might be useful both to estimate the heritability and to map
      the genetic loci responsible for the regulation of the trait. Family-based
      studies may estimate high heritability for thrombosis and quantitative traits
      regarding both platelet aggregation and blood coagulation. Some specific loci
      relevant to thrombosis have been identified, with some of them showing a direct
      pleiotropic effect on the risk of thrombosis. Haemostasis factors can be
      activated by inflammatory stimuli. Fibrinogen level is genetically correlated
      with C-reactive protein levels with a link for both traits on chromosomes 12 and
      21. Genes related to prostanoid biosynthesis, involved both in inflammation and
      thrombosis, show high heritability levels in both enzyme expression and
      prostanoid production. Considering that few large family-based linkage studies
      have as yet been performed on haemostasis and inflammation-related traits,
      additional studies are highly needed. We are performing a family-based linkage
      study on large pedigrees (750 subjects from 23 families with juvenile myocardial
      infarction and 31 control families), to identify genes responsible for
      quantitative traits involved in the pathway progressively going from inflammation
      to haemostasis, cell activation, thrombus formation and cardiovascular events.

PMID- 20692138
TI  - Polymorphism at the TRIB1 gene modulates plasma lipid levels: insight from the
      Spanish familial hypercholesterolemia cohort study.
AB  - BACKGROUND AND AIMS: rs17321515 SNP has been associated with variation in LDL-C,
      high density lipoprotein cholesterol and triglycerides concentrations. This
      effect has never been studied in patients with severe hypercholesterolemia.
      Therefore, our aims were to assess the association of the rs17321515 (TRIB1) SNP
      with plasma lipids concentrations and anthropometric variables and to explore the
      interaction between this SNP and some classic risk factors in patients with
      familial hypercholesterolemia (FH). METHODS AND RESULTS: rs17321515 SNP was
      genotyped in 531 subjects with genetic diagnosis of FH. Homozygous A/A had
      significantly higher waist circumference compared with G/G subjects (P = 0.006)
      and carriers of the minor allele G (P = 0.039). Interestingly, smokers homozygous
      for the A allele displayed higher plasma triglycerides concentrations (P =
      0.029), higher VLDL-C levels (P = 0.023) and higher TC/HDL-C ratio (P = 0.035)
      than carriers of the minor allele G. In addition, homozygous A/A with the
      presence of arcus cornealis displayed lower plasma ApoA-I levels (P = 0.024) and
      higher TC/HDL-C ratio (P = 0.046) than carriers of the minor allele G.
      CONCLUSIONS: Smoking status and presence of arcus cornealis modulate the effect
      of rs17321515 (TRIB1) polymorphism on plasma lipids levels in patients with FH.
      These results could explain the differences in the susceptibility to coronary
      heart disease in these patients.

PMID- 20692139
TI  - The impairment of metrial gland development in tamoxifen exposed rats.
AB  - We examined the sequential histopathological changes in the placenta from rats
      exposed to tamoxifen. Tamoxifen was administered intraperitoneally at doses of 0
      and 2 mg/kg/day on gestation days (GDs) 8, 9 and 10, and the placentas were
      sampled on GDs 11, 13, 15, 17, and 21. The fetal mortality rates in the tamoxifen
      group were increased up to 56%. However, there were no effects on the weights of
      live embryos/fetuses and their placentas. Histopathologically, the size of
      metrial gland in the tamoxifen group was reduced on all sampling times. The
      spiral arteries appeared less well developed in the hypoplastic metrial gland. A
      decrease in uterine natural killer (uNK) cells and mitotic uNK cells around the
      spiral arteries in the metrial gland was detected from GD 13 onward and on GDs 11
      and 13, respectively. There were no obvious changes in the labyrinth zone or
      basal zone. We consider that the anti-estrogen effect of tamoxifen inhibits the
      proliferation of decidualized endometrial stromal cells in the metrial gland and
      leads to inhibition of the proliferative activity of uNK cells, followed by
      defective development of spiral arteries, and metrial gland hypoplasia. It is
      assumed that the metrial gland hypoplasia might be involved in the tamoxifen
      induced embryo/fetus-toxicity.

PMID- 20692140
TI  - Budesonide added to formoterol contributes to improved exercise tolerance in
      patients with COPD.
AB  - BACKGROUND: Breathlessness and exercise intolerance frequently impact the daily
      life of patients with COPD. METHODS: This double-blind, multicentre, three-period
      crossover study randomised 111 patients with COPD (mean age 64 years, mean FEV(1)
      38% of predicted normal) to budesonide/formoterol 320/9 microg, formoterol 9
      microg or placebo, twice daily for 1 week, following a 1-week run-in period with
      1-week wash-out between treatments. Terbutaline (0.5 mg/dose) was used as needed.
      The primary efficacy variable was exercise endurance time (EET) at 75% peak work
      capacity with cycle ergometry assessed 1 h post-morning dose. RESULTS:
      Budesonide/formoterol prolonged EET 1 h post-morning dose versus formoterol by 69
      s (P < 0.005) and placebo by 105 s (P < 0.0001) and improved inspiratory capacity
      (IC) at isotime during exercise versus formoterol by 8% (P = 0.011) and placebo
      by 16% (P < 0.0001). Borg score at isotime was reduced by 0.48 (P = 0.12) and
      0.78 (P = 0.014) compared with formoterol and placebo, respectively. At the
      repeated cycle test 6 h after morning dose, the effect on EET still favoured
      budesonide/formoterol over formoterol and placebo, while the isotime IC and Borg
      score were similar but better than placebo for the active study drugs.
      Budesonide/formoterol and formoterol improved health status (St George's
      Respiratory Questionnaire total score: mean difference versus placebo -2.4 and 
      2.2, respectively). All treatments were well tolerated. CONCLUSIONS:
      Budesonide/formoterol resulted in a significant improvement in endurance time 1 h
      after the last morning dose in a 1-week treatment period versus formoterol and
      placebo. This study demonstrates, for the first time, the benefit of inhaled
      corticosteroids in addition to long-acting beta(2)-agonists on exercise tolerance
      in COPD patients. www.clinicaltrials.gov registration number: NCT00489853.

PMID- 20692141
TI  - The effect of challenge method on methacholine-induced changes in sensitivity and
      air trapping.
AB  - BACKGROUND: The methacholine challenge test performed with the tidal breathing
      method induces a greater fall in FEV(1) than the dosimeter method; however, the
      effect of the challenge method on methacholine-induced fall in FVC has not been
      investigated. OBJECTIVE: To determine the influence of the challenge method on
      methacholine-induced changes in FEV(1) and FVC. METHODS: Airway responsiveness to
      methacholine was determined by dosimeter method and tidal breathing method in 37
      subjects with suspected asthma. The dosimeter was modified to deliver an
      identical volume to that obtained with the tidal breathing method and the same
      nebulizer model was used for the two challenges. The response was expressed by
      the provocative concentration of methacholine causing a 20% fall in FEV(1)
      (PC(20)) and by the percent fall in FVC at the PC(20) value relative to FVC after
      saline inhalation. RESULTS: The PC(20) values obtained with the tidal breathing
      method and the dosimeter method were similar, with geometric mean values of 3.15
      (95%CI, 1.85-5.34 mg/mL) and 2.51 (1.37-4.61 mg/mL, P = 0.092), respectively. The
      percent fall in FVC at the PC(20) value obtained with the dosimeter was
      significantly greater than that obtained with the tidal breathing method, with
      mean values of 11.8 (95%CI, 10.0-13.5%) and 9.4 (95%CI, 8.1-10.8, P = 0.002),
      respectively. CONCLUSIONS: Differences in methacholine PC(20) values obtained
      with the two challenge methods recommended in guidelines may be overcome by
      introducing some technical modifications in the dosimeter method. However, the
      technical factors that affect methacholine sensitivity and air trapping are at
      least partially different.

PMID- 20692142
TI  - A novel process for ethanol or biogas production from cellulose in blended-fibers
      waste textiles.
AB  - A novel process has been developed for separation of the cellulose, i.e. cotton
      and viscose, from blended-fibers waste textiles. An environmentally friendly
      cellulose solvent, N-methylmorpholine-N-oxide (NMMO) was used in this process for
      separation and pretreatment of the cellulose. This solvent was mixed with blended
      fibers textiles at 120  degrees C and atmospheric pressure to dissolve the
      cellulose and separate it from the undissolved non-cellulosic fibers. Water was
      then added to the solution in order to precipitate the cellulose, while both
      water and NMMO were reused after separation by evaporation. The cellulose was
      then either hydrolyzed by cellulase enzymes followed by fermentation to ethanol,
      or digested directly to produce biogas. The process was verified by testing 50/50
      polyester/cotton and 40/60 polyester/viscose-blended textiles. The polyesters
      were purified as fibers after the NMMO treatments, and up to 95% of the cellulose
      fibers were regenerated and collected on a filter. A 2-day enzymatic hydrolysis
      and 1-day fermentation of the regenerated cotton and viscose resulted in 48 and
      50 g ethanol/g regenerated cellulose, which were 85% and 89% of the theoretical
      yields, respectively. This process also resulted in a significant increase of the
      biogas production rate. While untreated cotton and viscose fibers were converted
      to methane by respectively, 0.02% and 1.91% of their theoretical yields in 3 days
      of digestion, the identical NMMO-treated fibers resulted into about 30% of yield
      at the same period of time.

PMID- 20692143
TI  - Quantitative detection of DNA by autocatalytic enlargement of hybridized gold
      nanoprobes.
AB  - Quantitative detection of specific viral DNA has become a pressing issue for the
      earlier clinical diagnosis of viral infectious diseases. Therefore, in this
      paper, we report a simple, sensitive, and inexpensive quantitative approach for
      DNA detection based on the autocatalytic Au deposition of gold nanoprobes via the
      surface reduction of AuCl4- to Au0 on their surface in the presence of ascorbic
      acid (AA) and cetyltrimethylammonium bromide (CTAB). On this basis, signal
      enhancements in the absorbance intensity and kinetic behavior of gold enlargement
      in the aqueous phase have been well investigated and explained for the selection
      of analytical parameters. To achieve high sensitivity, magnetic particles
      conjugated with capture probes (PMPs) were employed for the collection of gold
      nanoprobes. After denaturated by ion a pH 11 solution, the amplified signals of
      gold nanoprobes, which is proportional to the concentration of the target DNA,
      could easily be confirmed by a UV-vis scanning spectrophotometer. Limit of
      detection could be obtained as low as 1.0 fM by this simple method.

PMID- 20692144
TI  - Surface plasmon resonance imaging (SPRi)-based sensing: a new approach in signal
      sampling and management.
AB  - Surface plasmon resonance imaging (SPRi) is at the forefront of optical sensing,
      allowing real-time and label free simultaneous multi-analyte measurements. It
      represents an interesting technology for studying a broad variety of affinity
      interactions with impact in chemistry, both in fundamental and applied research.
      Signal sampling and management is a key step in SPRi measurements to achieve
      successful performances. This work aims to develop a strategy for selecting the
      sensing areas, called Regions of Interest (ROIs), to be sampled for recording
      SPRi signals that could results in improved sensor performances. The approach has
      been evaluated using antigen-antibody interaction: anti-human IgGs are
      immobilized on the chip surface in an array format, while the specific ligand
      (hIgG antigen) is in solution. This approach has general applicability and
      demonstrates that rational selection of sensitive areas and standard management
      of SPRi data has dramatic impact on sensor behaviour. The criteria of the method
      are: (a) creation of high density maps of ROIs, (b) evaluation of the SPRi
      binding signals on all the ROIs during a pre-analysis step, (c) 3D elaboration of
      the results, and (d) ranking of the ROIs for their final selection in further
      biosensor analysis. Using standard solution of antigen, three different ROIs
      selection approaches have been compared for their analytical performances. The
      proposed innovative method results to be the best one for SPRi-based sensing
      applications.

PMID- 20692145
TI  - Structure effects of self-assembled Prussian blue confined in highly organized
      mesoporous TiO2 on the electrocatalytic properties towards H2O2 detection.
AB  - Here we report the derivatization of mesoporous TiO2 thin films for the
      preparation of H2O2 amperometric sensors. The coordination of the bifunctional
      ligand 1,10 phenantroline, 5,6 dione on the surface Ti(IV) ions provides open
      coordination sites for Fe(II) cations which are the starting point for the growth
      of a layer of Prussian blue polymer. The porous structure of the mesoporous TiO2
      allows the growth, ion by ion of the coordination polymer. Up to four layer of
      Prussian blue can be deposit without losing the porous structure of the film,
      which results in an enhanced response of these materials as H2O2 sensors. These
      porous confined PB modified electrodes are robust sensors that exhibit good
      reproducibility, environmental stability and high sensitivity towards H2O2
      detection.

PMID- 20692146
TI  - Detection of beta-amyloid peptide (1-16) and amyloid precursor protein (APP770)
      using spectroscopic ellipsometry and QCM techniques: a step forward towards
      Alzheimers disease diagnostics.
AB  - A highly sensitive method of spectroscopic ellipsometry in total internal
      reflection mode (TIRE) was exploited for detecting beta-amyloid peptide (Abeta(1
      16)) in the direct immune reaction with monoclonal DE2 antibodies (raised against
      Abeta(1-16)) electrostatically immobilised on the surface of gold. A rapid
      detection of Abeta(1-16) in a wide range of concentrations from 5 MUg/ml down to
      0.05 ng/ml was achieved using a cost-effective and label-free direct immunoassay
      format. TIRE dynamic spectral measurements proved that the immune reaction
      between DE2 monoclonal antibodies and Abeta(1-16) is highly specific with the
      affinity constant K(D)=1.46*10(-8) mol/l. The same DE2 antibodies were utilised
      for detection of amyloid precursor protein APP(770), a larger protein containing
      Abeta(1-16) domain, using the quartz crystal microbalance (QCM) measurements in
      liquid. A combination of QCM and TIRE kinetics results allowed the evaluation of
      the originally unknown concentration of APP(770) in complete medium solution
      containing other proteins, salts, and amino acids.

PMID- 20692147
TI  - Amplified QCM-D biosensor for protein based on aptamer-functionalized gold
      nanoparticles.
AB  - A highly sensitive quartz crystal microbalance with dissipation monitoring (QCM
      D) biosensor for protein was developed using aptamer-functionalized gold
      nanoparticles (Apt-GNPs) for amplification. Human alpha-thrombin, an important
      physiological protease found in blood, was chosen as the target protein. Captured
      by immobilized aptamers, thrombin was determined on-line using Apt-GNPs to
      enhance both frequency and dissipation signals. The fabricated sandwich of
      aptamer/thrombin/Apt-GNPs on chip surface was confirmed by atomic force
      microscopy (AFM). Compared to direct assay, the detection limit for thrombin was
      down to 0.1 nM, yielding about 2 orders of magnitude improvement in sensitivity.
      This aptamer-based QCM-D biosensor also showed good selectivity and repeatability
      in complex matrix. For the first time, the dual-signal enhancement of Apt-GNPs on
      QCM-D sensing was demonstrated, and such design could provide a promising
      detection strategy for proteins with two binding sites.

PMID- 20692148
TI  - Nonenzymatic free-cholesterol detection via a modified highly sensitive
      macroporous gold electrode with platinum nanoparticles.
AB  - A sensitive macroporous Au electrode with a highly rough surface obtained through
      the use of with Pt nanoparticles (macroporous Au-/nPts) is reported. It has been
      designed for nonenzymatic free-cholesterol biosensor applications. A macroporous
      Au-/nPts electrode was fabricated by electroplating Pt nanoparticles onto a coral
      like shaped macroporous Au electrode structure. The macroporous Au-/nPts
      electrode was physically characterized by field emission scanning electron
      microscopy (FESEM). It was confirmed that the Pt nanoparticles were well
      deposited on the surface of the macroporous Au electrode. The porosity and window
      pore size of the macroporous Au electrode were 50% and 100-300 nm, respectively.
      The electroplated Pt nanoparticle size was approximately 10-20 nm.
      Electrochemical experiments showed that the macroporous Au-/nPts exhibited a much
      larger surface activation area (roughness factor (RF)=2024.7) than the
      macroporous Au electrode (RF=46.07). The macroporous Au-/nPts also presented a
      much stronger electrocatalytic activity towards cholesterol oxidation than does
      the macroporous Au electrode. At 0.2 V, the electrode responded linearly up to a
      5 mM cholesterol concentration in a neutral media, with a detection limit of
      0.015 mM and detection sensitivity of 226.2 MUA mM(-1) cm(-2). Meanwhile,
      interfering species such as ascorbic acid (AA), acetaminophen (AP), and uric acid
      (UA), were effectively avoided. This novel nonenzymatic detection electrode has
      strong applications as an electrochemically based cholesterol biosensor.

PMID- 20692149
TI  - Selection of DNA aptamer against prostate specific antigen using a genetic
      algorithm and application to sensing.
AB  - In order to construct an aptasensor, aptamers that show high affinity for target
      molecules are required. While the systematic evolution of ligands by exponential
      enrichment (SELEX) is an efficient method for selecting aptamers, it sometimes
      fails to obtain aptamers with high affinity and so additional improvements are
      required. We applied a genetic algorithm (GA) to post-SELEX screening as an in
      silico maturation of aptamers. First, we pre-selected DNA aptamers against
      prostate specific antigen (PSA) through three rounds of SELEX. To improve the PSA
      binding ability of the aptamers, we carried out post-SELEX screening using GA
      with the pre-selected oligonucleotide sequences. For screening using GA, we
      replicated the oligonucleotide sequences obtained through SELEX, crossed over and
      mutated in silico resulting in 20 sequences. Those oligonucleotide sequences were
      synthesized and assayed in vitro. Then, the oligonucleotides were ranked
      according to PSA-binding ability and the top sequences were selected for the next
      cycle of GA operation. After GA operations, we identified the aptamer showing a
      48-fold higher PSA-binding ability than candidates obtained by SELEX. The
      dissociation constant (K(D)) of the obtained aptamer was estimated to be several
      tens of nM. We demonstrated sensing of PSA using the obtained aptamer and
      succeeded in sensing PSA concentrations between 40 and 100 nM. This is the first
      report of a DNA aptamer against PSA and its application to PSA sensing.

PMID- 20692150
TI  - Toward specific detection of Dengue virus serotypes using a novel modular
      biosensor.
AB  - Arthropod-borne diseases affect a significant portion of the world's population.
      Dengue fever, a viral disease carried by the Aedes aegypti mosquito, is one of
      the most wide-spread, with many fatalities evident each year. To date, Dengue
      viral diagnostic technologies have been too complex, time-consuming and expensive
      to be widely deployed, particularly in developing countries where the disease is
      most prevalent. Here we demonstrate a modular biosensor that is able to rapidly
      identify sequences associated with the Dengue virus genome. The biosensor
      consists of an oligonucleotide linker module, an aptamer/restriction endonuclease
      signal transducer and a fluorescent signalling molecule. The linker molecule has
      a simple stem/loop conformation and comprises a target-complementary moiety
      within the loop and a trigger moiety within the stem. When bound to the target
      nucleic acid, the trigger strand of the denatured stem can bind to the aptamer
      within the signal transducer. Disruption of the aptamer releases the restriction
      endonuclease EcoRI from aptamer-mediated inhibition. Active EcoRI is able to
      rapidly cleave multiple signalling molecules to generate a detectable signal. The
      biosensor was able to detect sequences derived from each of the four Dengue virus
      serotypes with a great degree of specificity. Along with sequences specific to
      each serotype, a pan-Dengue sequence, common to all serotypes, was also detected.

PMID- 20692151
TI  - Reagentless biosensor for hydrogen peroxide based on self-assembled films of
      horseradish peroxidase/laponite/chitosan and the primary investigation on the
      inhibitory effect by sulfide.
AB  - Horseradish peroxidase (HRP) was successfully incorporated into the
      laponite/chitosan (Chit)-modified glassy carbon electrode (GCE) using step-by
      step self-assembly. The self-assembly processes were monitored by X-ray
      photoelectron spectroscopy (XPS) and electrochemical impedance spectra (EIS).
      Direct electrochemistry and electrocatalysis of the self-assembled HRP were
      investigated. Cyclic voltammetry of HRP/laponite/Chit/GCE, in anaerobic phosphate
      buffer solution (0.025 M PBS, pH 7.0), displayed a pair of stable and quasi
      reversible peaks at potentials Epa=0.024 V and Epc=-0.132 V vs. SCE, attributed
      to the HRP-Fe(III)/HRP-Fe(II) redox couple. The electrochemical reaction of the
      HRP/laponite/Chit/GCE exhibited a surface-controlled electrode process. The
      electron transfer rate constant was estimated to be 1.82 s(-1). The self
      assembled HRP maintained its biological activity and exhibited an excellent
      electrocatalytic performance for the reduction of H2O2 with fast amperometric
      response (10 s), broad linear range (2.9*10(-5) to 1.4*10(-3) M), good
      sensitivity (19.7+/-0.5 mA M(-1) cm(-2)) and low detection limit (5*10(-6) M) at
      a signal-to-noise ratio of 3. Moreover, the inhibitory of sulfide to the self
      assembled HRP was also investigated.

PMID- 20692152
TI  - Biosensing of lipid-prion interactions: insights on charge effect, Cu(II)-ions
      binding and prion oligomerization.
AB  - The molecular mechanism involved in early stages of prion protein (PrP)
      conversion has been investigated using the chip based SPR technology, focusing on
      PrP interactions with membranes, either in its monomeric, oligomeric or Cu(II)
      ions bound forms. We observed a strong interaction between PrP and cell membrane
      models of different lipid compositions. Circular dichroism tests show that
      membrane-bound, oligomerized or Cu(II)-complexed PrP may adopt a beta-sheet-rich
      conformation. Moreover, upon PrP binding membrane vesicles may aggregate and/or
      be fragmented depending on vesicle net-charge and their lipid/raft composition.
      The whole study emphasizes the outstanding performance of the on-a-chip approach
      for the investigation of prion conversion and could be useful for developing
      sensor formats for prion assessments in biological samples.

PMID- 20692153
TI  - Studies on neuronal differentiation and signalling processes with a novel
      impedimetric biosensor.
AB  - The differentiation of neural cells is an important process during the
      development of the central nervous system. Studies on the mechanisms of the
      differentiation process is of special importance, e.g. in the field of
      regenerative medicine. In this contribution the cellular differentiation of gel
      matrix embedded neuronal cells was studied. The three-dimensional organization of
      neuronal cells represents a new cellular model system closer to the physiology
      than conventional two-dimensional cell cultures. Neuro2a (N2a) neuroblastoma
      cells were immobilized in different gel matrices and the grade of differentiation
      was compared. Furthermore, the impact of the cell number and selected
      differentiation factors were analyzed. Experimental results revealed that gel
      matrices based on collagen-laminin mixtures in contact with serum free medium
      enable neural differentiation. Therefore, collagen-laminin gels appear as a
      suitable three-dimensional model for drug screening in developmental
      neurobiology. Following optimization of the immobilization process, a novel
      impedimetric sensor and electrical impedance spectroscopy technique was applied
      to on-line monitor the differentiation process by means of changes in the
      dielectric and conductive properties. Experimental results showed an increase in
      the impedance magnitude that can be mainly attributed to differentiating cells
      accompanied by an increase in the specific resistivity of the bare gel mixture.

PMID- 20692154
TI  - Microbial communities involved in electricity generation from sulfide oxidation
      in a microbial fuel cell.
AB  - Simultaneous electricity generation and sulfide removal can be achieved in a
      microbial fuel cell (MFC). In electricity harvesting from sulfide oxidation in
      such an MFC, various microbial communities are involved. It is essential to
      elucidate the microbial communities and their roles in the sulfide conversion and
      electricity generation. In this work, an MFC was constructed to enrich a
      microbial consortium, which could harvest electricity from sulfide oxidation.
      Electrochemical analysis demonstrated that microbial catalysis was involved in
      electricity output in the sulfide-fed MFC. The anode-attached and planktonic
      communities could perform catalysis independently, and synergistic interactions
      occurred when the two communities worked together. A 16S rRNA clone library
      analysis was employed to characterize the microbial communities in the MFC. The
      anode-attached and planktonic communities shared similar richness and diversity,
      while the LIBSHUFF analysis revealed that the two community structures were
      significantly different. The exoelectrogenic, sulfur-oxidizing and sulfate
      reducing bacteria were found in the MFC anodic chamber. The discovery of these
      bacteria was consistent with the community characteristics for electricity
      generation from sulfide oxidation. The exoelectrogenic bacteria were found both
      on the anode and in the solution. The sulfur-oxidizing bacteria were present in
      greater abundance on the anode than in the solution, while the sulfate-reducing
      bacteria preferably lived in the solution.

PMID- 20692155
TI  - One-chip electronic detection of DNA hybridization using precision impedance
      based CMOS array sensor.
AB  - This paper describes a label-free and fully electronic detection method of DNA
      hybridization, which is achieved through the use of a 16*8 microarray sensor in
      conjunction with a new type of impedance spectroscopy constructed with standard
      complementary metal-oxide-semiconductor (CMOS) technology. The impedance-based
      method is based on changes in the reactive capacitance and the charge-transfer
      resistance after hybridization with complementary DNA targets. In previously
      published label-free techniques, the measured capacitance presented unstable
      capacitive properties due to the parallel resistance that is not infinite and can
      cause a leakage by discharging the charge on the capacitor. This paper presents
      an impedance extraction method that uses excitation by triangular wave voltage,
      which enables a reliable measurement of both C and R producing a highly sensitive
      sensor with a stable operation independent of external variables. The system was
      fabricated in an industrial 0.35-MUm 4-metal 2-poly CMOS process, integrating
      working electrodes and readout electronics into one chip. The integrated readout,
      which uses a parasitic insensitive integrator, achieves an enlarged detection
      range and improved noise performance. The maximum average relative variations of
      C and R are 31.5% and 68.6%, respectively, after hybridization with a 1 MUM
      target DNA. The proposed sensor allows quantitative evaluation of the molecule
      densities on the chip with distinguishable variation in the impedance. This fully
      electronic microsystem has great potential for use with bioanalytical tools and
      point-of-care diagnosis.

PMID- 20692156
TI  - Challenges in the use of 1D nanostructures for on-chip biosensing and
      diagnostics: a review.
AB  - This review outlines the use of one-dimensional nanostructures (1D-NS) for the
      detection of biomolecules on a chip. The materials discussed here include carbon
      nanotubes, metallic and semiconducting nanowires and nanochannels. While
      nanotubes and naowires have predominantly been used as electrical detectors,
      nanochannels are promising frameworks for optical detection in applications such
      as separation, preconcentration and DNA mapping. The primary expectation for all
      the three types of 1D-NS lies in the promise for ultimate single molecule
      detection. Furthermore, the electrical double layer governs the physics behind
      biosensing in all the three systems. The review starts by shedding light on the
      advantages arising due to the use of 1D nanostructures, followed by a discussion
      of fundamental aspects such as double layer effects and sensing methodologies.
      After this, the three kinds of 1D-NS are introduced. The main focus of the review
      is an in-depth analysis of the current achievements in the field and the major
      challenges that are to be overcome for the widespread use of such nanostructures
      in applications such as lab-on-a-chip devices and point-of-care diagnostics.

PMID- 20692157
TI  - Sequential taxane and anthracycline-containing neoadjuvant regimens: the
      sequential order impact.
AB  - BACKGROUND: One can consider as a standard neoadjuvant treatment for breast
      cancer, the sequence of 4 cycles of anthracycline-based chemotherapy followed by
      4 cycles of docetaxel. Based on the belief that the sequence order between
      anthracycline and taxane might be of interest, this study assessed the impact of
      the sequence order. METHODS: One hundred and twenty three patients with breast
      cancer were treated with neoadjuvant chemotherapy in 5 oncologic centers between
      2003 and 2007. This study compared 65 patients treated with 4 cycles of docetaxel
      followed by 4 cycles of anthracycline-based chemotherapy (cohort T), versus
      another cohort of 58 patients treated with 4 cycles of anthracycline-based
      chemotherapy followed by 4 cycles of docetaxel (cohort A). RESULTS: The overall
      dose intensity of docetaxel and clinical complete responses were significantly
      higher in cohort T. No statistically significant differences were observed in
      terms of conservative surgeries or histological responses. The sequence of
      chemotherapy did not significantly influence other treatment-related toxicities.
      Mild neurotoxicity was higher in patients treated in cohort T. Anemias (>=Grade
      1) were higher in cohort A (52% versus 81%; p = 0.0008). CONCLUSION: The present
      study failed to identify an impact of the sequence of taxane administration on
      the efficacy. Nevertheless, starting neoadjuvant chemotherapy by taxane reduces
      the occurrence of anemia. These findings might allow a selection of the sequence
      order based on the toxicity profile.

PMID- 20692158
TI  - Patients' experiences of intensive care diaries--a focus group study.
AB  - The aim of the study was to explore patients' experiences and perceptions of
      receiving intensive care diaries. A focus group and intensive care diaries for
      four former ICU patients were analysed to understand what works and what needs
      further development for patients who receive a diary. The study had a
      triangulated approach and group dynamics were described as the focus group was
      used to explore agreement and disagreement among the participants. Little is
      known about the content of intensive care diaries and their usefulness and
      meaning for the patients. The participants in our study agreed that the diary
      alone provided incomplete information and reading the diary did not necessarily
      bring back memories, but helped complete their story. The patients needed to know
      what they had gone through in ICU and wished to share their story with their
      family. We conclude that diaries might help post-ICU patients to gradually
      construct or reconstruct their own illness narrative, which is pieced together by
      their fragmented memory, the diary, the pictures, the hospital chart and the
      accounts from family and friends.

PMID- 20692159
TI  - The Toe Walking Tool: a novel method for assessing idiopathic toe walking
      children.
AB  - BACKGROUND: The diagnosis of idiopathic toe walking (ITW) is achieved by the
      exclusion of all medical causes associated with toe walking. In order to identify
      children with this gait type, an online Toe Walking Tool questionnaire was
      developed that utilized questions to identify healthy idiopathic toe walkers and
      excluded those who toe walk as a result of a medical condition. METHOD: A Delphi
      panel process was conducted to establish the relevance and validity of the
      questions. A group of 10 allied health professionals assessed 12 children
      utilizing the Toe Walking Tool. A kappa was calculated to determine reliability.
      RESULTS: Clinicians agreed the questionnaire was an appropriate and effective
      assessment tool. The tool proved valid in that no child tested who toe walked as
      a result of a medical condition was able to progress through the testing process.
      Testing group of practitioners had a Fleiss Kappa agreement of 0.928. CONCLUSION:
      The Toe Walking Tool is a valid and reliable method of assessing children who
      present to the general allied health clinician with toe walking. This tool can
      assist with the decision of when to refer a child for further specialist
      investigation of their toe walking.

PMID- 20692160
TI  - Kinematic analysis and dexterity evaluation of upper extremity in activities of
      daily living.
AB  - The redundant kinematic structure of upper extremity (UE) provides it with
      increased dexterity in activities of daily living (ADL). Most functional tasks
      during ADL can be implemented in various positions; however, only some routine
      trajectories are employed in healthy humans. Exploring motion ability and
      analyzing dexterity are clinically helpful in understanding the motion principles
      of the UE during ADL. The aim of this work was to develop a qualitative and
      quantitative evaluation method for unconstrained movement analysis of the UE. Ten
      healthy male volunteers with no UE pathology were tested based on a kinematic
      model proposed in this paper which follows the ISB recommendations. The dexterity
      measure (DM) and manipulability ellipsoid (ME) were used to evaluate the
      dexterity distribution and motion ability in space. Representative dexterity
      trajectories and corresponding ellipsoids were determined for the ADL tasks. The
      results of the study showed that there was a most dexterous posture for each
      functional task. The UE movement followed an approximately optimal kinematic
      performance trajectory when the hand moved in front of the thorax during ADL.

PMID- 20692161
TI  - Age-related differences in cognitive and postural dual-task performance.
AB  - The present experiment assessed, in children aged 7-11 and in adults, whether
      postural control is affected by cognitive processes and vice versa. Using a dual
      task, the level of difficulty of a Stroop task and bipedal quiet stance varied
      alternatively. We hypothesised that the interference between cognitive and
      postural tasks was non-linear during childhood with a so-called turning point
      around 8. Twenty-seven children 7- to 11-years-old and nine adults participated
      in the experiments. The postural task was executed in a semi-tandem Romberg
      position. Two cognitive conditions (congruent and non-congruent Stroop
      conditions) and two postural situations (with and without perturbed
      proprioceptive inputs) were presented simultaneously with the instruction to
      respond as correctly as possible while remaining as stable as possible. Results
      showed that, in the Vib condition, CoP mean velocity decreased with the increased
      cognitive complexity only in children aged 7. Moreover, the data showed a non
      linear decrease in postural sway during childhood, whatever the level of
      complexity of the cognitive and/or postural tasks. CoP mean amplitude and mean
      velocity decreased between 7 and 8, and again between age 11 and adults. This
      study (1) confirmed that the interference between mental activity and postural
      control can be attributed mainly to attentional limitations, (2) showed the
      existence of a turning point around 8 in the development of this capacity, and
      (3) suggested that the mature level of attentional resources was not reached
      until age 11. Further research is needed to assess the development of attention
      implied in a cognitive/postural dual-task, including probably another so-called
      turning point during the adolescence.

PMID- 20692162
TI  - Normative EMG activation patterns of school-age children during gait.
AB  - Gait analysis is widely used in clinics to study walking abnormalities for
      surgery planning, definition of rehabilitation protocols, and objective
      evaluation of clinical outcomes. Surface electromyography allows the study of
      muscle activity non-invasively and the evaluation of the timing of muscle
      activation during movement. The aim of this study was to present a normative
      dataset of muscle activation patterns obtained from a large number of strides in
      a population of 100 healthy children aged 6-11 years. The activity of Tibialis
      Anterior, Lateral head of Gastrocnemius, Vastus Medialis, Rectus Femoris and
      Lateral Hamstrings on both lower limbs was analyzed during a 2.5-min walk at free
      speed. More than 120 consecutive strides were analyzed for each child, resulting
      in approximately 28,000 strides. Onset and offset instants were reported for each
      observed muscle. The analysis of a high number of strides for each participant
      allowed us to obtain the most recurrent patterns of activation during gait,
      demonstrating that a subject uses a specific muscle with different activation
      modalities even in the same walk. The knowledge of the various activation
      patterns and of their statistics will be of help in clinical gait analysis and
      will serve as reference in the design of future gait studies.

PMID- 20692163
TI  - A systematic review of the effect of ageing and falls history on minimum foot
      clearance characteristics during level walking.
AB  - Minimum foot clearance (MFC) is the minimum vertical distance between the lowest
      point of the foot of the swing leg and the walking surface during the swing phase
      of the gait cycle. MFC is a gait variable that is linked to the mechanism of a
      trip because reduced MFC for a given step during walking increases the
      susceptibility to tripping on an unseen obstacle or due to undetected changes in
      surface height. Given that tripping is a common cause of falls in older persons,
      this review was undertaken to determine whether ageing and/or history of falls in
      older adults influences MFC characteristics during level walking. Studies that
      assessed MFC characteristics including measures of central tendency (mean and/or
      median), variability (linear and non-linear measures) and shape (skewness,
      kurtosis) of the MFC distribution were included in the review. The final yield
      from a search of seven electronic research databases was 12 unique articles that
      met all the inclusion criteria. Ageing does not appear to alter measures of
      central tendency or shape of the MFC distribution. However greater MFC
      variability was observed in older compared to younger adults and older fallers
      compared to older non-fallers in the majority of studies. Greater MFC variability
      may contribute to increased risk of trips and associated falls in older compared
      to young adults and older fallers compared to older non-fallers.

PMID- 20692164
TI  - Extraventricular neurocytoma of the vermis in a child.
AB  - Neurocytomas are rare neoplasms, composed of uniform round cells with neuronal
      differentiation. We report a rare extraventricular neurocytoma (EVN) in a 5-year
      old boy who presented with headache and vomiting. His MRI brain showed a vermian
      mass. The histopathological examination and immunohistochemistry revealed it to
      be an EVN. We report this patient for the rarity of the condition and the EVN
      mimicking a medulloblastoma on imaging. This tumor needs to be differentiated
      from a medulloblastoma as the former has a better prognosis.

PMID- 20692165
TI  - Early neurological change in patients with spontaneous supratentorial
      intracerebral hemorrhage.
AB  - The frequency and causes of neurological change that occurs in patients within 24
      hours after the onset of intracerebral hemorrhage (ICH), as well as their
      relationship to outcome, have seldom been reported. This study evaluated 184
      patients with supratentorial ICH and neurological deterioration or improvement;
      measuring their level of consciousness (LOC) and motor skills the day after
      admission using the National Institutes of Health Stroke Scale. Nineteen patients
      (10%) deteriorated and 114 (62%) improved. Patient age, hematoma volume, and
      change in hematoma volume were independent predictors of early neurological
      improvement (p < 0.05). Independent predictors of 1-month functional outcome were
      age, LOC score at admission, motor score at admission, and change in motor score
      the day after admission (p < 0.05). Approximately 70% of the patients showed
      early neurological change. Observing early changes in hemiparesis was important
      for predicting functional outcome.

PMID- 20692166
TI  - A comparison of the outcome of aneurysmal subarachnoid haemorrhage before and
      after the introduction of an endovascular service.
AB  - There has been a rapid change from predominantly surgical to endovascular
      treatment of ruptured intracranial aneurysms giving the opportunity to assess
      change in patient outcome during this transition. We identified and followed 139
      patients with subarachnoid haemorrhage (SAH) treated in the year prior to (group
      1) and following (group 2) the introduction of an endovascular service in a
      retrospective, cross-sectional study. A total of 78.7% of patients in group 1
      underwent surgical treatment, 10.7% underwent endovascular treatment and 10.7%
      received no treatment, whereas patients in group 2 received 29.7%, 65.7% and
      4.7%, respectively. MRS scores were obtained in 91% of patients in group 1 and in
      89% of patients in group 2. A total of 30.7% and 24.0% of patients had a poor
      outcome in groups 1 and 2 respectively (p=0.34). The overall change in the
      management of ruptured cerebral aneurysms in the post-International Subarachnoid
      Aneurysm Trial (ISAT) era has not significantly changed cross-sectional outcome,
      although absolute differences appear to reflect difference in outcome noted in
      the ISAT.

PMID- 20692167
TI  - Acute paresthesia in a patient with migraine.
AB  - Ergot-containing medications are widely used to treat migraine patients in some
      countries but nowadays intoxication is only reported rarely. We report a 35-year
      old woman who presented with acute paresthesia of the extremities. An angiogram
      revealed diffuse vasospasm of the femoral arteries bilaterally and the right
      brachial artery. History taking disclosed a possible interaction between
      ergotamine and macrolide antibiotics. The patient's symptoms improved rapidly
      after discontinuation of the offending medication and administration of
      vasodilators. This report aims to remind physicians that catastrophic adverse
      effects can develop through unrecognized drug interactions, even with widely
      prescribed medications given in safe dosages. The importance of a detailed drug
      history and knowledge of drug interactions cannot be overemphasized in the
      diagnosis of ergotism.

PMID- 20692168
TI  - The transzygomatic approach.
AB  - We aim to describe the technical details of the transzygomatic approach to
      intracranial surgery. The incision begins at the level of the inferior border of
      the zygomatic arch, anterior to the tragus, and extends towards the contralateral
      pupillary line. A subgaleal and interfascial dissection is performed. Then, the
      zygomatic arch is vertically sectioned twice and mobilized downwards, together
      with the masseter muscle. Next, a fronto-temporo-sphenoidal craniotomy is
      performed and complete exposure of the anterior temporal dura achieved. Thus, the
      surgical possibilities are: (i) intradural access to the middle fossa; (ii)
      intradural pretemporal access to the basal cisterns; (iii) intradural
      transtemporal access to the insular region; and (iv) extradural access to the
      middle fossa. The transzygomatic approach offers excellent exposure to the floor
      of the middle fossa and the lateral wall of the cavernous sinus (both
      intradurally and extradurally). Also, combined with a pretemporal approach, it
      affords a good view of the interpeduncular cistern; and using a transtemporal
      approach, it provides good access to the insular region.

PMID- 20692169
TI  - Anti-tuberculosis treatment for Devic's neuromyelitis optica.
AB  - There are no specific treatments for patients with acute, severe neurological
      deficits caused by neuromyelitis optica (NMO) who fail to recover after treatment
      with high-dose corticosteroids. We evaluated the clinical response of anti
      tuberculosis treatment (ATT) in patients suffering from steroid-refractory NMO,
      and investigated the correlation between NMO and tuberculous infection of the
      central nervous system (CNS). We conducted this prospective, controlled study in
      southern China. Twelve patients with steroid-refractory NMO were monitored during
      ATT and compared with a control group of 13 patients with the same type of NMO
      who received current standard therapies. A molecular diagnostic test was carried
      out and Extended Disability Status Scale (EDSS) score analysis, visual acuity,
      the number of relapses and MRI changes were evaluated at study entry and after 1
      and 2years of therapy. ATT may lead to the recovery of important neurological
      functions and all our patients responded positively to therapy. EDSS score and
      visual acuity improved and abnormalities in the spinal cord, observed by MRI,
      markedly decreased over time. ATT also significantly reduced the rate of relapse.
      By comparison, in the control group, a significant clinical deterioration was
      observed, and patients did not show favourable EDSS scores and MRI changes. This
      study suggests that CNS infection with Mycobacterium tuberculosis is an important
      cause of NMO.

PMID- 20692170
TI  - Bilateral psoas abscesses caused by methicillin-resistant Staphylococcus aureus
      (MRSA) after posterolateral fusion of the lumbar spine.
AB  - Psoas abscess following spine surgery is a rare condition that can be overlooked
      or delayed as a result of its vague clinical manifestations. Gone unchecked, it
      can lead to severe morbidity and even death. We present a 71-year-old female
      patient who developed bilateral psoas abscess immediately following L2 through S1
      posterior instrumented fusion. The patient underwent CT-guided percutaneous
      drainage of the bilateral psoas abscess and blood cultures revealed methicillin
      resistant Staphylococcus aureus (MRSA) sensitive to vancomycin. Following
      surgical re-exploration, debridement and removal of part of the instrumentation,
      the patient received antibiotic treatment for 12 weeks and at 1-year follow-up
      the patient continues asymptomatic.

PMID- 20692171
TI  - Angiographic analysis of venous drainage and a variant basal vein of Rosenthal in
      spontaneous idiopathic subarachnoid hemorrhage.
AB  - The aim of this study was to examine the clinical characteristics and
      angiographic findings of spontaneous idiopathic subarachnoid hemorrhage (ISAH)
      and to compare these with those of aneurysmal SAH (ASAH). We retrospectively
      reviewed the clinical characteristics and venograms of 118 consecutive patients
      with ISAH during the past 10years for possible abnormalities in venous
      structures. Also, 57 patients with ASAH during the past 4years were examined.
      Patients with ISAH showed low frequency of hypertension and no patient suffered
      from an episode of re-bleeding, or delayed ischemic deficits. Physical actions,
      including varieties of the Valsalva maneuver, were the causes of ISAH in 17
      (29.8%) patients. Compared with patients with ASAH, patients with ISAH showed a
      significant difference in the drainage patterns of the basal vein of Rosenthal
      (BVR) (p=0.001). In addition, whereas a linearly decreasing trend toward the
      primitive type was evident in ASAH, each drainage pattern was distributed evenly
      in ISAH (linear by linear association, p=0.000). In this study, the primitive
      drainage pattern of BVR has a relationship with ISAH compared to ASAH. The way in
      which this venous configuration might influence bleeding remains unknown.

PMID- 20692172
TI  - Multi-level corpectomies and reconstruction via a single posterolateral approach.
AB  - The surgical treatment of ventral spinal canal compression has traditionally
      required either an anterior or combined anterior-posterior decompression and
      stabilization. These types of approaches carry a significant morbidity and may
      not be appropriate for all patients. We report our experience with multi-level
      corpectomies and reconstruction performed via a single, posterolateral approach.
      A retrospective review was performed of six consecutive patients at a single
      institution who were treated for ventral multi-level spinal cord compression via
      a single posterolateral approach. All six patients underwent reconstruction and
      stabilization with an expandable cage and posterior fixation. Five patients had
      metastatic cancer with spinal cord compression and one patient had osteomyelitis
      with a ventral epidural abscess and vertebral body collapse. All patients
      underwent 2-level corpectomies. Pre-operative and post-operative neurologic
      function and stabilization construct integrity were analyzed. All patients had
      successful decompression and stabilization and there were no hardware
      complications. Three peri-operative complications were encountered: post
      operative pleural effusion needing thoracostomy drainage, transient leg paresis
      that resolved at 2months and a post-operative wound infection needing operative
      debridement. At last follow-up all patients had improvement or stabilization of
      their neurological function. Long-term follow-up was limited by the progression
      of metastatic disease and death in all the patients with cancer. This study
      demonstrates that symptomatic improvement can be achieved in select patients
      requiring multi-level corpectomies when using a single posterolateral approach
      with expandable cage reconstruction and posterior stabilization.

PMID- 20692173
TI  - Synthesis and ribonuclease A inhibition activity of resorcinol and phloroglucinol
      derivatives of catechin and epicatechin: Importance of hydroxyl groups.
AB  - The reported ribonuclease A inhibitory activity of the green tea extracts
      prompted us to synthesize novel catechin/epicatechin based conjugates with
      resorcinol and phloroglucinol with the aim to increase the number of phenolic OH
      groups. These are found to be more effective inhibitors of ribonuclease A as
      compared to catechin and epicatechin thus indicating the importance of number of
      phenolic OH groups for the inhibition of ribonucleolytic activity. Fluorescence
      studies have been carried out to evaluate the binding parameters. The protein
      ligand docking studies are also performed to gain insight into the protein
      polyphenols interactions. The epicatechin based polyphenols 1 and 2 also showed
      inhibition of angiogenin-induced angiogenesis, as determined by chorioallantoic
      membrane (CAM) assay.

PMID- 20692174
TI  - Synthesis, biological evaluation, and docking studies of novel heterocyclic
      diaryl compounds as selective COX-2 inhibitors.
AB  - Three novel series of diaryl heterocyclic derivatives bearing the 2-oxo-5H-furan,
      2-oxo-3H-1,3-oxazole, and 1H-pyrazole moieties as the central heterocyclic ring
      were synthesized and their in vitro inhibitory activities on COX-1 and COX-2
      isoforms were evaluated using a purified enzyme assay. The 2-oxo-5H-furan
      derivative 6b was identified as potent COX inhibitor with selectivity toward COX
      1 (COX-1 IC(50)=0.061 microM and COX-2 IC(50)=0.325 microM; selectivity index
      (SI)=0.19). Among the 1H-pyrazole derivatives, 11b was found to be a potent COX-2
      inhibitor, about 38 times more potent than Rofecoxib (COX-2 IC(50)=0.011 microM
      and 0.398 microM, respectively), but showed no selectivity for COX-2 isoform.
      Compound 11c demonstrated strong and selective COX-2 inhibitory activity (COX-1
      IC(50)=1 microM, COX-2 IC(50)=0.011 microM; SI= approximately 92). Molecular
      docking studies of compounds 6b and 11b-d into the binding sites of COX-1 and COX
      2 allowed to shed light on the binding mode of these novel COX inhibitors.

PMID- 20692175
TI  - A genetically encoded sensor for H2O2 with expanded dynamic range.
AB  - Hydrogen peroxide is an important second messenger controlling intracellular
      signaling cascades by selective oxidation of redox active thiolates in proteins.
      Changes in intracellular [H(2)O(2)] can be tracked in real time using HyPer, a
      ratiometric genetically encoded fluorescent probe. Although HyPer is sensitive
      and selective for H(2)O(2) due to the properties of its sensing domain derived
      from the Escherichia coli OxyR protein, many applications may benefit from an
      improvement of the indicator's dynamic range. We here report HyPer-2, a probe
      that fills this demand. Upon saturating [H(2)O(2)] exposure, HyPer-2 undergoes an
      up to sixfold increase of the ratio F500/F420 versus a threefold change in HyPer.
      HyPer-2 was generated by a single point mutation A406V from HyPer corresponding
      to A233V in wtOxyR. This mutation was previously shown to destabilize interface
      between monomers in OxyR dimers. However, in HyPer-2, the A233V mutation
      stabilizes the dimer and expands the dynamic range of the probe.

PMID- 20692176
TI  - Preparation of (90)YCl(3) radiopharmaceutical precursor for nuclear medicine
      using technology of centrifugal extractors.
AB  - Separation of (90)Y from a parent solution of (90)Sr-(90)Y in 0.5 M nitric acid
      by two-stage liquid-liquid extraction has been investigated using centrifugal
      extractors. The extraction agent used was 0.25 M di-(2-ethylhexyl)phosphoric acid
      (D2EHPA) in n-dodecane. Back-extraction used 5 M HCl. Evaporation of HCl was
      performed in a rotary vacuum evaporator. Experience gained during the design,
      construction and running of more than 100 hot separations is presented. A short
      description of analytical methods used and results of the determination of
      chemical, radionuclidic and radiochemical purities and sterility are given.

PMID- 20692177
TI  - Elemental analysis of Egyptian crude oils by INAA using rabbit irradiation system
      at ETRR-2 reactor.
AB  - Instrumental neutron activation analysis (INAA) using rabbit irradiation system
      at ETRR-2 reactor was utilized to analyze some elements namely Na, Mg, Al, Cl, V,
      Mn, In, and Br in four different crude petroleum samples from different oil
      fields in the Suez-Gulf region of Egypt. The INAA was performed by four different
      standardization methods. Namely absolute, single comparator based on effective
      cross section concept, single comparator based on k(0,Au) factors, and that based
      on k(0,ic) factors defined versus any suitable internal comparator method. A
      FORTRAN computer program was written to calculate the extracted concentrations by
      these methods. A reasonable agreement between the obtained results was noticed.

PMID- 20692179
TI  - First successful trans-catheter aortic valve implantation through ascending aorta
      using Edwards SAPIEN THV system.
AB  - Trans-catheter aortic valve implantation is rapidly becoming an established
      modality of treatment for patients with critical aortic stenosis who are high
      risk for conventional aortic valve replacement. This approach also has its
      limitations; however, with growing experience and improvements in the delivery
      system, it may be possible to overcome these limitations. We describe a case
      where conventional trans-catheter approaches, that is, transfemoral or trans
      apical using the Edwards THV system, were not possible but successful
      implantation was achieved through the trans-aortic route.

PMID- 20692178
TI  - Recurrent spontaneous pneumothorax in a patient with Birt-Hogg-Dube syndrome.
AB  - Recurrent spontaneous pneumothorax is a disorder often managed by thoracic
      surgeons. Most etiologies are benign in nature; however, there are several
      syndromes that are associated with potentially fatal pulmonary or systemic
      manifestations. One such example is Birt-Hogg-Dube syndrome, a rare inheritable
      syndrome characterized by papular skin lesions involving the scalp, head, face
      and neck; pulmonary cysts; and a propensity to develop renal carcinoma. In our
      report, we describe a patient, who was diagnosed with Birt-Hogg-Dube syndrome
      after presenting with a history of recurrent spontaneous pneumothorax, and a
      family history of spontaneous pneumothorax and renal cell carcinoma. This case is
      of particular interest to the cardiothoracic surgery community as the patient
      described as well as several of his family members were managed by multiple
      thoracic surgeons, who did not appreciate the diagnosis.

PMID- 20692180
TI  - Effect of functional electrical stimulation on the effort and walking speed,
      surface electromyography activity, and metabolic responses in stroke subjects.
AB  - OBJECTIVE: To investigate the effects of functional electrical stimulation (FES)
      combined with conventional rehabilitation program on the effort and speed of
      walking, the surface electromyographic (sEMG) activity and metabolic responses in
      the management of drop foot in stroke subjects. METHODS: Fifteen patients with a
      drop foot resulting from stroke at least 3 months prior to the start of the trial
      took part in this study. All subjects were treated 1h a day, 5 days a week, for
      12 weeks, including conventional stroke rehabilitation program and received 30
      min of FES to the tibialis anterior (TA) muscle of the paretic leg in clinical
      settings. Baseline and post-treatment measurements were made for temporal and
      spectral EMG parameters of TA muscle, walking speed, the effort of walking as
      measured by physiological cost index (PCI) and metabolic responses. RESULTS: The
      experimental results showed a significant improvement in mean-absolute-value
      (21.7%), root-mean-square (66.3%) and median frequency (10.6%) of TA muscle EMG
      signal, which reflects increased muscle strength. Mean increase in walking speed
      was 38.7%, and a reduction in PCI of 34.6% between the beginning and at end of
      the trial. Improvements were also found in cardiorespiratory responses with
      reduction in oxygen consumption (24.3%), carbon dioxide production (19.9%), heart
      rate (7.8%) and energy cost (22.5%) while walking with FES device. CONCLUSIONS:
      The results indicate that the FES may be a useful therapeutic tool combined with
      conventional rehabilitation program to improve the muscle strength, walking
      ability and metabolic responses in the management of drop foot with stroke
      patients.

PMID- 20692181
TI  - Analysis of the relationship between the rise-time and the amplitude of single
      fibre potentials in human muscles.
AB  - Using the core-conductor theory, a single fibre action potential (SFAP) can be
      expressed as the convolution of a biolectrical source and a weight function. In
      the Dimitrov-Dimitrova (D-D) SFAP convolutional model, the first temporal
      derivative of the intracellular action potential (IAP) is used as the source. The
      present work evaluates the relationship between the SFAP peak-to-peak amplitude
      (V(pp)) and peak-to-peak interval (rise-time, RT) at different fibre-to-electrode
      distances using simulated signals obtained by the D-D model as well as real
      recordings. With a single fibre electrode, we recorded 63 sets of consecutive
      SFAPs from the m. tibialis anterior of four normal subjects. The needle was
      intentionally moved whilst recording each SFAP set. We used the observed changes
      in RT and V(pp) within each SFAP set as a point of reference with which to
      evaluate how closely the relationship between RT and V(pp) provided by the D-D
      model reflects real data. We found that half of the recorded SFAP sets had rise
      times higher than those generated by the D-D model. We also showed the influence
      of the IAP spatial length on the sensitivity of RT and V(pp) with radial
      distance. The study reveals some inaccuracies in simulated SFAPs whose origin
      might be related to the assumptions made in the core-conductor theory.

PMID- 20692183
TI  - Comparative feasibility of myocardial velocity and strain measurements using 2
      different methods with transesophageal echocardiography during cardiac surgery.
AB  - OBJECTIVE: To assess the feasibility and correlation between tissue Doppler and
      speckle tracking imaging when measuring myocardial velocity, strain, and strain
      rate with transesophageal echocardiography. DESIGN: A prospective, observational
      study. SETTING: An academic tertiary-referral hospital. PARTICIPANTS: Patients
      undergoing elective heart surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: Velocity, strain, and strain rate were measured using both techniques in
      the inferior and anterior walls in transgastric views for radial motion and in
      the lateral, septal, anterior, and inferior walls in midesophageal views for
      longitudinal motion. Nineteen patients and 304 myocardial segments were studied.
      Overall, tissue Doppler was found to be more successful than speckle tracking in
      measuring myocardial velocity, whereas strain and strain rate measurements were
      achieved with comparable success using either method. Tissue Doppler was more
      successful than speckle tracking for radial cardiac motion, and the highest
      success rates were achieved with this method (93.4% v 59.2% for velocity, p <
      0.001; 78.9% v 59.2% for strain, p = 0.01; and 73.7% v 59.2% for strain rate, p =
      0.09). Good correlation between tissue Doppler and speckle tracking was shown in
      4 myocardial segments: radial midinferior, radial basal inferior, radial basal
      anterior, and longitudinal basal septum (R = 0.6-0.82, p < 0.05). CONCLUSIONS:
      The correlation between tissue Doppler and speckle tracking with transesophageal
      echocardiography appears valid when predominantly confined to segments moving in
      a radial direction adjacent to the ultrasound transducer. Tissue Doppler
      echocardiography of radial cardiac motion appears to be the most feasible
      technique of measuring myocardial velocity, strain, and strain rate during
      cardiac surgery.

PMID- 20692182
TI  - Enhancing the effectiveness of community stroke risk screening: a randomized
      controlled trial.
AB  - Stroke risk factors are routinely assessed in community screening programs;
      however, the rate of patient follow-up for health care once risk factors are
      identified is known to be low. This study was conducted to test the effectiveness
      of a brief behavioral telephonic intervention in an ongoing community stroke
      prevention screening program on health care seeking for stroke risk. A total of
      227 participants with 2 or more stroke risk factors were randomly allocated to
      either an attention control arm or a behavioral intervention arm. The control
      group received standard information on risk and advice, whereas the intervention
      group received a brief Health Belief Model telephonic intervention designed to
      motivate care-seeking. The effect of treatment on the participants who completed
      a health care visit for stroke risk concerns was assessed using logistic
      regression. Cox survival analysis was used to compare time to physician visit
      between the 2 groups. Participants in the intervention arm were 1.85 times more
      likely to visit a primary care physician than controls. At 3 months, 69.2% of
      subjects in the intervention arm and 52.9% of those in the controls arm reported
      a new primary care visit after screening (P = .02), with 56.0% in the
      intervention arm and 38.4% in the control arm reporting a primary care visit
      specifically to discuss the stroke screening results (P < .01). Our data indicate
      that the brief, low-cost, motivational intervention effectively promoted
      adherence to screening advice and merits further testing.

PMID- 20692184
TI  - The effects of levetiracetam on urinary 15f-2t-isoprostane levels in epileptic
      patients.
AB  - PURPOSE: We aimed to investigate the effects of levetiracetam on oxidative stress
      which is one of the new antiepileptic drugs in epileptic patients. METHODS: The
      study consisted of 21 patients with cryptogenic partial epilepsy. We determined
      the urinary 15F-2t-isoprostane levels of the 30 patients which is a marker of
      oxidative stress. Morning urine samples were collected from the patients before
      beginning LEV and after 3 months treatment. Of these patients 9 were excluded
      from the study that had seizure history in the last 1 month. Urinary levels of 15
      F2t-isoprostane determined by ELISA initially and after 3 months treatment for
      each patient. RESULTS: Mean age of the 21 patients was 29.6, of these 11 were
      females and 10 males. Mean urinary 15F-2t-isoprostane level of the patients was
      876 +/- 447 ng/mg Cr before the treatment of LEV. After 3 months treatment the
      mean 15F-2t-isoprostane level of the patients was 1560 +/- 630. The patients had
      significantly higher levels of urinary 15F-2t-isoprostane when compared with
      initial levels (p = 0.025). CONCLUSION: Our results showed the increase of
      urinary 15F-2t-isoprostane levels in epileptic patients whom were treated with
      LEV which may indicate that LEV induces the oxidative stress in epileptic
      patients.

PMID- 20692185
TI  - Fibrous cortical defect (nonossifying fibroma) of the mandibular ramus: report of
      2 cases.
AB  - Fibrous cortical defect, also known as metaphyseal fibrous defect and
      nonossifying fibroma, among other terms, is a benign, non-neoplastic
      proliferative process that is relatively common in the long bones of skeletally
      immature adolescents. Although the lesion is thought to be a developmental
      abnormality or defect, the exact etiopathogenesis is largely unknown. The lesion
      has a limited growth potential and good treatment outcome. This process is very
      rare in the gnathic bones, and only a few sporadic case reports are documented.
      This article presents the clinicopathologic features of 2 additional cases and
      reviews the relevant literature in attempt to identify key features and
      facilitate rendering definitive diagnosis for this rare entity.

PMID- 20692186
TI  - Influence of chlorhexidine application at longitudinal push-out bond strength of
      fiber posts.
AB  - OBJECTIVE: The objective of this study was to evaluate the influence of
      chlorhexidine application after dentin phosphoric acid etching at immediate and
      long-term bond strength of a fiber post cemented to root dentin. STUDY DESIGN:
      Seventy-two single-rooted, human upper teeth were selected. After phosphoric acid
      etching, each group received a different dentin treatment: no pretreatment or
      chlorhexidine 0.2% or 2.0%. Three-step etch-and-rinse adhesive and dual-cured
      resin cement was used to cementation procedure. Half of the teeth were submitted
      to push-out bond strength test after 24 hours and the other half after 6 months.
      Data were analyzed by 2-way ANOVA and Tukey. RESULTS: Chlorhexidine application
      had no influence on bond strength when teeth were stored at the same aging time
      (P > .05). The storage time significantly decreased the bond strength values of
      24 hours to 6 months in all groups (P < .05). CONCLUSION: After 6 months,
      chlorhexidine application did not effectively arrest bond strength degradation of
      fiber posts cemented in human roots.

PMID- 20692187
TI  - Clinical experiences of digital model surgery and the rapid-prototyped wafer for
      maxillary orthognathic surgery.
AB  - OBJECTIVE: The aim of this study was to present our clinical experience regarding
      the production and accuracy of digitally printed wafers for maxillary movement
      during the bimaxillary orthognathic surgery. STUDY DESIGN: Fifty-five consecutive
      patients requiring maxillary orthognathic surgery were included in this study.
      The plan for digital model surgery (DMS) was dictated by the surgical plans for
      each clinical case. We carried out digital model mounting, DMS, wafer printing,
      and confirmation of the accuracy of the procedure. RESULTS: Moving the reference
      points to the target position in DMS involved a mean error of 0.00-0.09 mm. The
      mean errors confirmed by the model remounting procedure with the printed wafer by
      DMS were 0.18-0.40 mm (for successful cases; n = 42) and 0.03-1.04 mm (for poor
      cases; n = 3). CONCLUSION: The accuracies of the wafers by DMS were similar to
      those for wafers produced by manual model surgery, although they were less
      accurate than those produced by DMS alone. The rapid-prototyped interocclusal
      wafer produced with the aid of DMS can be an alternative procedure for maxillary
      orthognathic surgery.

PMID- 20692188
TI  - Scanning electron microscope evaluation of chlorhexidine gel and liquid
      associated with sodium hypochlorite cleaning on the root canal walls.
AB  - OBJECTIVE: The aim of this study was to evaluate, by scanning electronic
      microscopy (SEM), the cleaning of the root canal walls after instrumentation and
      irrigation with 2.5% sodium hypochlorite (NaOCl) associated with 2% chlorhexidine
      (CHX) gel or liquid, combined or not with 17% ethylenediamine tetra-acetic acid
      (EDTA). STUDY DESIGN: Sixty single-root human teeth were subjected to
      standardized root canal instrumentation with different irrigants (n = 10): G1)
      NaOCl + CHX liquid; G2) NaOCl + CHX liquid + EDTA + saline solution; G3) NaOCl +
      CHX gel; G4) NaOCl + CHX gel + EDTA + saline solution; G5) saline solution; G6)
      saline solution + EDTA. After instrumentation, the teeth were prepared for SEM
      analysis (*500 and *2,000) to evaluate the cleaning of the cervical, middle, and
      apical thirds. The area analyzed was quantified according to the percentage of
      open and closed tubules, and data were statistically analyzed by analysis of
      variance and Tukey tests (P = .05). RESULTS: The number of open tubules was
      highest in G4 in all root thirds, showing statistically significant difference
      from G1, G2, and G5 (P < .05). G1 presented higher quantity of closed tubules
      significant than G2. CONCLUSION: Irrigation with NaOCl and CHX gel followed by
      EDTA and saline solution produced greater cleaning of the root canal walls.

PMID- 20692189
TI  - Sunitinib may raise the risk of bisphosphonate-related osteonecrosis of the jaw:
      presentation of three cases.
AB  - OBJECTIVE: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a serious
      side effect of bisphosphonate (BP) medication. Tooth extractions are the most
      frequent causes for BRONJ. In some cases BRONJ is observed spontaneously, with
      some anatomic sites carrying a higher risk. Sunitinib, a tyrosine kinase
      inhibitor, is established in renal cell carcinoma and is known to lead to oral
      mucositis as a side effect, which in BP patients may additionally raise the risk
      of BRONJ. STUDY DESIGN: We present 3 patients with renal cell carcinoma under BP
      medication who developed BRONJ during and after sunitinib medication. RESULTS: In
      2 patients, BRONJ was linked to the occurrence of mucositis after sunitinib
      intake. The third patient showed relapse of completely healed BRONJ lesions
      shortly after resumption of a sunitinib therapy. CONCLUSIONS: Oral mucositis
      during chemotherapy may raise the risk of BRONJ in cancer patients with BP
      medication. Especially in renal cell carcinoma patients under sunitinib therapy
      and intravenous BP medication, oral mucositis should be observed closely because
      it could be a risk factor for BRONJ.

PMID- 20692190
TI  - Fixation, registration, and image-guided navigation using a thermoplastic facial
      mask in electromagnetic navigation-guided radiofrequency thermocoagulation.
AB  - OBJECTIVE: For fixation, registration, and image-guided navigation, the aim of
      this study was to evaluate a thermoplastic facial mask with plastic markers in
      achieving frameless stereotactic radiofrequency thermocoagulation (RFT). STUDY
      DESIGN: A thermoplastic facial mask was remolded according to each subject's
      face. Six markers were placed on the surface and 6 inside. Series of 1.25-mm- and
      2.5-mm-slice computerized tomography (CT) scans were made to provide radiologic
      data. During the phantom study, each plastic sphere inside was selected in turn
      as the target for frameless stereotaxy. The clinical Hartel puncture of the
      foramen ovale (FO) was imitated using an electromagnetic navigation system.
      Navigation-guided RFT was tried in 3 patients. RESULTS: The mean location error
      was 1.29 mm (SD +/- 0.39 mm). No significant difference (P > .05) was proven
      between 1.25-mm and 2.5-mm CT slice acquisition for the image datasets used. The
      FO punctures in clinical trials were successful and confirmed by CT. CONCLUSIONS:
      Registration and fixation via a fiducial marker-based thermoplastic facial mask
      is accurate and feasible for use in navigation-guided RFT.

PMID- 20692191
TI  - Case report: endodontic and surgical treatment of an upper central incisor with
      external root resorption and radicular cyst following a traumatic tooth avulsion.
AB  - In the age group between 6 and 12 years, trauma to the upper incisors happens
      frequently. In the case of avulsion, a replantation is the state-of-the-art
      treatment; however, it may lead to several complications, particularly if
      suitable posttraumatic management is not carried out. External cervical
      resorptions as well as apical granuloma and cysts due to microbial contamination
      of the root canal are common complications. In the presented trauma case, a
      conservative approach was chosen to treat a large cystic lesion combined with
      cervical and apical resorptions. After initial placement of Ledermix and calcium
      hydroxide into the root canal, a marsupialization with the temporary insertion of
      an obturator was performed. The gradual reduction led to a fast recovery of the
      bony defect and a root canal filling was placed. The 2-year follow-up showed an
      improved condition. All adjacent teeth remained vital during the course of the
      treatment.

PMID- 20692192
TI  - Unusual oral complications of herpes zoster infection: report of a case and
      review of literature.
AB  - A case of herpes zoster infection with unusual oral complications involving the
      mandibular division of the trigeminal nerve is presented. The post-herpetic
      complications of osteonecrosis, spontaneous exfoliation of teeth, and subsequent
      pathologic fracture of mandible in the absence of concurrent predisposing factors
      in a 65-year-old man are demonstrated. Forty-one cases with osteonecrosis and
      spontaneous exfoliation of teeth previously presented in the literature are
      reviewed. This is the first report of pathologic fracture after herpes zoster
      infection.

PMID- 20692193
TI  - Minor salivary gland squamous cell carcinoma of the lower lip demonstrating
      striking perineural invasion.
AB  - Squamous cell carcinomas (SCC) of minor salivary gland origin are extremely rare.
      We present an unusual case of a 29-year-old female patient who presented with a
      well-differentiated SCC of minor salivary gland origin arising in the lower lip.
      Wedge resections of the lip, including bilateral mental nerve excision, were
      required to clear the tumor because of striking pathological evidence of
      perineural invasion distant from the primary tumor site.

PMID- 20692194
TI  - Partial glutathione reductase deficiency as a cause of diverse clinical
      manifestations in a family with unstable hemoglobin (Hemoglobin Hana, beta63(E7)
      His-Asn).
AB  - Hemoglobin Hana [beta63(E7) His-Asn] is an unstable hemoglobin variant that was
      described in a Czech proband and her sister with Heinz body hemolytic anemia. The
      mother bearing the same mutation was asymptomatic; nevertheless, all three
      carriers had the same proportion of the mutant globin chains. Assessment of
      several erythrocyte antioxidant parameters revealed that both symptomatic
      children, unlike their asymptomatic mother, had significantly decreased
      glutathione reductase (GR) activity. Their GR activities were restorable in vitro
      by flavin adenine dinucleotide. The riboflavin supplementation improved their
      glutathione metabolism and ameliorated their hemolysis. Pre- and post-treatment
      assessment of the B(2) vitamers indicated suboptimal pre-treatment vitamin B(2)
      status in both children. This study provides evidence that partial GR deficiency
      may alter the clinical manifestation of an unstable hemoglobinopathy.

PMID- 20692195
TI  - Anti-NMDA-receptor encephalitis in a 3 year old patient with chromosome 6p21.32
      microdeletion including the HLA cluster.
AB  - Anti-NMDA-receptor encephalitis was initially described as a paraneoplastic
      disorder in young women with ovarian teratoma. We report on a 3-year-old boy who
      developed anti-NMDA-receptor encephalitis one month after a respiratory
      infection. Moreover, array-comparative genomic hybridization in this patient
      revealed an inherited microdeletion in chromosomeband 6p21.32, including the HLA
      DPB1 and HLA-DPB2 genes. The clinical relevance of this microdeletion is
      discussed.

PMID- 20692196
TI  - [Loss of quality of life in family caregivers of stroke patients: an entity to be
      considered].
AB  - INTRODUCTION: Among stroke consequences highlights the negative impact on the
      informal carers' health related quality of life (HRQoL). OBJECTIVES: To identify
      HRQoL dimensions most greatly affected in stroke caregivers and establish
      relations with dependent variables of survivors and caregivers. METHODS:
      Transversal study of 215 informal caregivers of stroke survivors (1:3 man/woman,
      mean age 63.6 (+/-11.03) years). Main outcome measure was health perception
      assessed with the Short Fom 36 (SF-36). Clinical and demographic data of stroke
      patients were also registered. Statistical tests used were Chi-square, t-Student
      test and Spearman correlation coefficient. RESULTS: Vitality and general health
      were the most affected dimensions perceived by caregivers. In comparison with the
      Spanish general population, female caregivers aged 45-54 years presented a
      significant reduction in the SF-36 subscales of vitality (p=0.003), social
      function (p=0.01), emotional role (p=0.038) and mental health (p=0.002). Female
      caregivers aged 55-64 years also showed a significant reduction in social
      function (p=0.027) and emotional role (p=0.024). Male caregivers did not present
      significant lower HRQoL. CONCLUSIONS: Caregiving experience has a negative impact
      on HRQoL, specially middle-aged female caregivers. Some carer physical and
      psychological characteristics (depression, musculoskeletal pain, time spent on
      caring) and survivor disability shown to influence carers outcomes. Caregivers
      play an important role in the recovery of stroke patients, so that the
      identification of strategies which help them to cope with the stroke might avoid
      that the role of caring results in a loss of quality of life.

PMID- 20692197
TI  - Cardiovascular complications in type 1 diabetes mellitus.
AB  - Although the issue of cardiovascular complications in type 2 diabetic patients is
      widely discussed, and recommendations for such screening are available, it is
      less common to do so for type-1 diabetes. Yet, independent of age, the mortality
      rate due to ischaemic cardiac disease is higher among type 1 diabetic patients
      (both male and female) than in the general population. Type 1 diabetic patients
      have certain specific characteristics related not only to atherosclerotic plaque
      and cardiovascular risk factors, but also to their capacity for physical activity
      and to the prevention of cardiovascular complications induced by hypoglycaemia.

PMID- 20692198
TI  - Ultrasound-promoted synthesis of novel spirooxindolo/spiroacenaphthen dicyano
      pyrrolidines and pyrrolizidines through regioselective azomethine ylide
      cycloaddition reaction.
AB  - Novel dicyano functionalised spiropyrrolidine and spiropyrrolizidine were
      synthesized from the reaction of various arylidenemalononitrile Knoevenagel
      adducts with non-stabilized azomethine ylides generated from
      isatin/acenaphthenequinone and sarcosine/N-phenylglycine/proline. The reactions
      were carried out under both conventional heating and ultrasonic irradiation
      conditions. In general, improvement in rates and yields were observed when the
      reactions were carried out under sonication compared with classical conditions.
      The regio and stereochemistry of the products was established by single crystal X
      ray structure and spectroscopic techniques.

PMID- 20692199
TI  - Differential sensing of sugars by colorimetric arrays.
AB  - While the complexes between boronic acids and diols have been studied for
      decades, researchers continue to design new and interesting methods to use these
      interactions to produce saccharide sensors that are more sensitive and selective.
      Herein we discuss how the use of pattern-based colorimetric arrays from a
      collection of crossreactive sensors have been developed as new differential
      sensing platforms for sugars and related saccharides.

PMID- 20692201
TI  - Theoretical studies of molecular structure and vibrational spectra of melaminium
      acetate acetic acid solvate monohydrate.
AB  - The molecular geometry and vibrational frequencies of melaminium acetate acetic
      acid solvate monohydrate in the ground state have been calculated by using the
      Hartree-Fock (HF) and density functional method (B3LYP) with 6-31++G(d,p) basis
      set. The results of the optimized molecular structure are presented and compared
      with the experimental X-ray diffraction. The molecule contains the weak hydrogen
      bonds of N-H...O and O-H...O types, and those bonds are calculated with HF and
      DFT method. The computed vibrational frequencies were used to determine the types
      of molecular motions associated with each of the experimental bands observed. In
      addition, calculated results are related to the linear correlation plot of
      computed data versus experimental geometric parameters and IR data.

PMID- 20692202
TI  - The consistency analysis of different semiempirical calculations on second- and
      third-order nonlinear optical properties of donor-acceptor chromophores
      containing alpha-cyan.
AB  - The static and frequency dependent average polarizability (<alpha>), first- and
      second-hyperpolarizabilities (<beta> and <gamma>) and HOMO and LUMO energies of
      donor-acceptor chromophores containing alpha-cyan (1a-c) have been investigated
      by using the AM1, MNDO, MNDO-d, PM3, RM1 and PM6 methods within a time-dependent
      Hartree-Fock (TDHF) approaches. The electronic properties of 1a-c have been
      reported by employing two-state model calculated at ZINDO/S-SCI, PM3-SCI and RM1
      SCI methods. Also, the molecular hardness (eta) and electronegativity (chi)
      parameters have been obtained by using molecular frontier orbital energies. The
      <alpha>, <beta>, <gamma> HOMO, LUMO energies, eta and chi parameters have been
      investigated with respect to the choice of different semiempirical methods. The
      variation graphics of beta, beta(0), eta and chi parameters according to the
      different semiempirical methods are presented. Furthermore, the variation
      graphics of beta(0) with regard to the mu(eg), Deltamu and lambda(eg) are
      displayed. The frontier molecular orbital and electrostatic potential pictures of
      1a-c using ZINDO/S-SCI level have been examined. The results of 1a-c display
      significant second- and third-order molecular nonlinearity.

PMID- 20692200
TI  - Targeting miRNAs involved in cancer stem cell and EMT regulation: An emerging
      concept in overcoming drug resistance.
AB  - Although chemotherapy is an important therapeutic strategy for cancer treatment,
      it fails to eliminate all tumor cells due to intrinsic or acquired drug
      resistance, which is the most common cause of tumor recurrence. Emerging evidence
      suggests an intricate role of cancer stem cells (CSCs) and epithelial-mesenchymal
      transition (EMT)-type cells in anticancer drug resistance. Recent studies also
      demonstrated that microRNAs (miRNAs) play critical roles in the regulation of
      drug resistance. Here we will discuss current knowledge regarding CSCs, EMT and
      the role of regulation by miRNAs in the context of drug resistance, tumor
      recurrence and metastasis. A better understanding of the molecular intricacies of
      drug-resistant cells will help to design novel therapeutic strategies by
      selective targeting of CSCs and EMT-phenotypic cells through alterations in the
      expression of specific miRNAs towards eradicating tumor recurrence and
      metastasis. A particular promising lead is the potential synergistic combination
      of natural compounds that affect critical miRNAs, such as curcumin or
      epigallocatechin-3-gallate (EGCG) with chemotherapeutic agents.

PMID- 20692203
TI  - Clinical severity of respiratory adenoviral infection by serotypes in Korean
      children over 17 consecutive years (1991-2007).
AB  - BACKGROUND: Human adenoviruses (HAdVs) are important causes of acute respiratory
      tract illness in children. OBJECTIVES: To evaluate the risk factors for severe
      respiratory HAdV infections and the temporal change in case-severity in relation
      to HAdV types. STUDY DESIGN: From January 1991 to December 2007, respiratory HAdV
      infections of Korean children requiring hospitalization or an emergency room
      visit were included. An episode of HAdV infection requiring an intensive care
      unit stay, use of mechanical ventilation and/or death was designated as a severe
      infection. The medical records were reviewed retrospectively. RESULTS: A total of
      428 respiratory HAdV infections were included in the clinical analysis. The mean
      age of patients was 2.6 years. The most frequent diagnosis was a lower
      respiratory tract infection (312/428, 72.9%), and 44% of respiratory HAdV
      infections occurred in patients with underlying co-morbidities. Fifteen percent
      of clinical events resulted in severe HAdV infections with a case-fatality rate
      of 5.1%. HAdV types 7 and 8 were associated with severe infections, after
      adjusting for co-morbidity and the age of patients (adjusted OR 8.5 and 15.1,
      respectively, by a logistic regression model). The case-severity of HAdV-7
      associated with lower respiratory tract infections has decreased over time,
      coinciding with the decreasing size of subsequent epidemics after a large
      outbreak (P for trend = 0.003). CONCLUSIONS: HAdV types 7 and 8 were independent
      risk factors for severe respiratory HAdV infections. In addition, the overall
      severity of HAdV-7 associated lower respiratory tract infections has shown a
      decreasing trend, which may reflect increasing level of herd immunity.

PMID- 20692204
TI  - The riddle of the sphinx: Sleep, pain, and depression.

PMID- 20692206
TI  - IDH mutations in glioma and acute myeloid leukemia.
AB  - The systematic sequencing of glioblastoma multiforme (GBM) genomes has identified
      the recurrent mutation of IDH1, a gene encoding NADP(+)-dependent isocitrate
      dehydrogenase 1 (IDH1) that catalyzes the oxidative decarboxylation of isocitrate
      yielding alpha-ketoglutarate (alpha-KG). Subsequent studies have confirmed
      recurrent IDH1 and IDH2 mutations in up to 70% of low-grade glioma and secondary
      GBM, as well as in 10% of acute myeloid leukemia (AML) cases. The heterozygous
      somatic mutations at arginine R132 (IDH1) and at R140 or R172 (IDH2) in the
      enzyme active site confer a gain of function to the enzymes, which can both
      produce the metabolite 2-hydroxyglutarate. This review surveys the prevalence of
      IDH mutations in cancer and explores current mechanistic understanding of IDH
      mutations with implications for diagnostic and therapeutic development for the
      treatment of gliomas and AML.

PMID- 20692205
TI  - Lessons for cardiac regeneration and repair through development.
AB  - Cell-based regenerative strategies have the potential to revolutionize the way
      cardiovascular injury is treated, but successful therapies will require a precise
      understanding of the mechanisms that dictate cell fate, survival and
      differentiation. Recent advances in the study of cardiac development hold promise
      for unlocking the keys for successful therapies. Using mouse models and embryonic
      stem cells, researchers are uncovering cardiac progenitor cells in both embryonic
      and adult contexts. Furthermore, the signaling molecules and transcriptional
      regulators that govern these cells and their behavior are being revealed. Here,
      we focus on the recent advances in these areas of cardiac developmental research
      and their impact on the expanding field of regenerative medicine.

PMID- 20692207
TI  - Preimplantation genetic diagnosis after 20 years.
AB  - Preimplantation genetic diagnosis (PGD) should not be an option only for the few
      couples at risk of serious genetic conditions who can afford it. We appear to
      have lost sight of the original driving force behind the development of PGD,
      which is that most couples who carry a serious genetic disorder find it more
      acceptable to choose to conceive with healthy embryos tested in-vitro at
      preimplantation stages of development within the first week following
      fertilization, even if that means discarding those diagnosed as affected. It has
      been shown using cystic fibrosis as an example, that the cost savings to the US
      healthcare system of providing free IVF-PGD to all carrier couples compared to
      the lifetime costs of medical treatment for patients affected by this disease,
      run to dozens of billions of dollars. With the increasing emphasis in medicine on
      early diagnosis and prevention of disease together with the availability of new
      molecular genetic diagnostic tools, a national IVF-PGD programme seems to be the
      next step in modern health care.

PMID- 20692208
TI  - Nonconvulsive status epilepticus and the postictal state.
AB  - Postictal symptoms, because of activation of inhibitory systems, have to be
      distinguished from ongoing ictal activity. The categorical concept of pure ictal
      and pure postictal symptoms cannot be supported by clinical observation alone.
      Differentiation between postictal and ictal behavioral phenomena can be difficult
      even with the use of electroencephalography, as clear-cut definitions of ictal
      and postictal changes are not available. Five different aspects can be
      considered: (1) hallucinatory symptoms recorded during and after a seizure, (2)
      prolonged postictal confusional states, (3) prolonged postictal psychotic states,
      (4) epileptic and other encephalopathies, and (5) coma with or without clinical
      signs of nonconvulsive status epilepticus. Presenting symptoms and conceptual
      considerations are presented in this review.

PMID- 20692209
TI  - Suprathreshold heat pain response is associated with clinical pain intensity for
      patients with shoulder pain.
AB  - Quantitative sensory testing (QST) has become commonly used for the assessment of
      pain in subjects with clinical conditions. However, there is no consensus about
      which type of QST is the best predictor of clinical pain responses. The purposes
      of this study were to determine: a) the QST measure with the strongest
      association with clinical pain intensity; and b) if the QST measure continued to
      predict clinical pain intensity in a model including relevant psychological
      factors. Fifty-nine patients seeking treatment for shoulder pain underwent
      experimental pain assessment involving heat and pressure stimuli. The patients
      also completed validated questionnaires for pain intensity, pain catastrophizing,
      anxiety, and depression. The 5th pain rating in a series of suprathreshold heat
      pain stimuli accounted for a significant amount of variance in clinical pain
      intensity, with no other QST measure contributing to the model. The 5th pain
      rating remained a significant contributor to clinical pain intensity when
      psychological factors were included in the model. Furthermore, subjects with
      elevated 5th pain rating, pain catastrophizing, and depression scores had higher
      clinical pain intensity ratings in pre- and postoperative assessments. These data
      suggest that assessment of pain should include suprathreshold heat stimuli and
      psychological factors separately, and a combination of these factors may be
      predictive of pain intensity outcomes. PERSPECTIVE: The current study provides
      evidence for a suprathreshold heat pain response as a clinically relevant QST
      measure for patients with shoulder pain, even after psychological factors were
      considered. The present findings suggest that the 5th pain rating from a series
      of suprathreshold stimuli, pain catastrophizing, and depression might play a role
      in predicting pain intensity outcomes.

PMID- 20692210
TI  - Utility of the anesthetic test dose to avoid catastrophic injury during cervical
      transforaminal epidural injections.
AB  - BACKGROUND CONTEXT: Reports of serious complications from cervical transforaminal
      epidural corticosteroid injections often consider accidental intra-arterial
      injection the most likely mechanism of injury. As a result, many physicians have
      instituted methods to prevent intravascular injections. Routine use of the
      anesthetic test dose is one such method. The utility of the anesthetic test dose
      in this function has not been characterized in the current literature. PURPOSE:
      The aim of this study was to determine the utility of injecting an anesthetic
      test dose before cervical transforaminal epidural corticosteroid injection and
      estimate the rate of false-negative intravascular contrast injection using live
      fluoroscopy and digital subtraction angiography (DSA). STUDY DESIGN: Two-center
      retrospective study. PATIENT SAMPLE: A consecutive cohort of men and women, ages
      of 23 to 83, who underwent cervical transforaminal epidural injection and
      received the anesthetic test dose after contrast injection was negative for
      vascular uptake, observed using live fluoroscopy or DSA. OUTCOME MEASURES:
      Response to the anesthetic test dose was documented in each procedure note and
      recorded as either positive or negative. METHODS: Records of three physiatrists
      at two academic spine centers (Center A and Center B) were reviewed to identify
      all patients who received a cervical transforaminal epidural injection during the
      preceding 5 years, resulting in a cohort of consecutively treated patients at
      each center. Each patient record was reviewed for demographics, indication for
      injection, procedure level and side, needle gauge, use of DSA, volume and type of
      anesthetic test dose used, and result of test dose injection. The test dose was
      considered positive if the following occurred: agitation or other sudden central
      nervous system change; gross motor deficits and/or paresthesias in the trunk,
      legs, or contralateral arm; systemic symptoms of anesthetic toxicity including
      cardiac arrhythmia, perioral numbness, metallic taste, dizziness, and/or ringing
      in the ear. For analysis, injections were separated into groups to compare
      results at Center A to Center B and to compare injections that used DSA to those
      that did not. The incidence of a positive response was calculated as a percentage
      from the total number of injections in the group. Differences between groups were
      analyzed for statistical significance using the Fisher exact test. RESULTS: Six
      hundred seventy-eight injections were included. Of these, 349 were performed at
      Center A with test doses given after contrast injection under live fluoroscopy.
      The remaining 329 were performed at Center B, 183 also using live fluoroscopy,
      and 146 using DSA. The overall incidence of a positive anesthetic test dose was
      0.59% (4/678). There was no significant difference between the incidence at each
      of the two centers (0.86% [3/349] vs. 0.30% [1/329]; p=.63). The overall
      incidence after live fluoroscopy was 0.75% (4/532) and after DSA was 0% (0/146),
      but this difference was not statistically significant (p=.58). Positive symptoms
      elicited by test dose administration included midneck and contralateral arm pain,
      metallic taste, dizziness, tachycardia, full body paresthesias, auditory changes,
      slurred speech, and motor ataxia. In all four cases with a positive response, the
      procedure was immediately terminated, symptoms resolved, and no lasting
      complications were observed. CONCLUSIONS: The routine use of an anesthetic test
      dose appears to be safe and capable of detecting potentially dangerous
      intravascular injections undetected by conventional techniques. Positive
      responses occur in a small portion of those who receive the test dose injection.
      Further studies are required to determine the optimal dose and concentration of
      anesthetic to be used and the time required for observation after test dose
      administration.

PMID- 20692211
TI  - High-dose rate brachytherapy alone in postoperative soft tissue sarcomas with
      close or positive margins.
AB  - PURPOSE: In the management of soft tissue sarcomas, perioperative radiation
      therapy has been used to reduce the risk of local recurrence after resection.
      However, a significance of postoperative high-dose rate brachytherapy (HDRBT)
      remains to be studied. Retrospective analysis was performed to elucidate the role
      of postoperative HDRBT. METHODS AND MATERIALS: Twenty-five patients with 26 soft
      tissue sarcoma lesions underwent postoperative HDRBT using (192)Ir remote
      afterloader without external beam radiation therapy. Ninety-two percent of the
      lesions were Grade 2 or 3 malignancies, and 50% were resected with positive
      surgical margins. The remaining 50% had very close margins. Fourteen lesions were
      treated for local recurrences after previous resections. Applicators of HDRBT
      were placed during the operation to include only the tumor bed excluding surgical
      scars. Applied dose was mainly 36Gy/6 fractions/3 d b.i.d. RESULTS: Five-year
      local recurrence-free survival was 78.2% in all the 26 lesions. Recurrences were
      not seen within the treated volume of HDRBT. Two groups were defined according to
      the marginal status and number of previous operations. Group 1 was the lesions
      with a positive margin and foregoing resections. The remaining lesions were
      classified as Group 2. Five-year local recurrence-free survival was 43.8% and
      93.3% in Group 1 and Group 2, respectively with a statistically significant
      difference (p=0.004). CONCLUSIONS: Postoperative HDRBT was effective in
      controlling local lesions; but in Group 1 lesions, addition of a wide field
      external beam radiation therapy seems to be necessary to improve the local
      control rate.

PMID- 20692213
TI  - Stem cells and cancer - the promise and puzzles.

PMID- 20692212
TI  - Dynamic intraoperative dosimetry for prostate brachytherapy using a nonisocentric
      C-arm.
AB  - PURPOSE: To evaluate a prototypical system of dynamic intraoperative dosimetry
      for prostate brachytherapy using registered ultrasound and fluoroscopy (RUF) with
      a nonisocentric C-arm (GE OEC, Salt Lake City, UT) and to compare intraoperative
      dosimetry of RUF as well as ultrasound-based seed localization (USD) with Day 0
      CT dosimetry. METHODS: Seed positions were independently determined using RUF and
      USD. RUF uses a radio-opaque fiducial for registration to ultrasound and 3
      dimensional reconstruction of seeds relative to prostate using nonisocentric C
      arm fluoroscopy. Postimplant CT was performed on Day 0. Squared differences
      between dosimetric measures for RUF vs. CT and USD vs. CT were calculated and
      mean squared differences evaluated. Paired t test was used to evaluate which
      method was more closely aligned with CT. Accuracies of USD and RUF compared with
      CT were estimated using a nonparametric approach. RESULTS: Six patients were
      treated and compared with USD. RUF identified areas of underdosage
      intraoperatively in all patients and median 5 additional seeds were placed. In 40
      of 42 measures, RUF was equally or more closely correlated with CT than USD. USD
      showed statistically significant variation from CT for 6 of 7 parameters compared
      with 1 of 7 parameters for RUF. Mean squared differences from CT were
      significantly smaller for RUF in 4 of 7 parameters compared with USD.
      CONCLUSIONS: Dynamic intraoperative dosimetry is possible with a conventional
      nonisocentric C-arm. Compared with an USD method, RUF-based intraoperative
      dosimetry was more closely aligned with immediate postimplant CT. RUF identified
      areas of underdosage, which were not detected using USD.

PMID- 20692214
TI  - Extended posterior auricular artery flap for coverage of a large temporo-parietal
      defect.
AB  - We present a case with a large 5*8 cm full-thickness defect in the temporo
      parietal region, which was managed with an extended posterior auricular artery
      based flap in one stage. The flap was shaped like a 'gandasa' (an axe-like
      agricultural implement used in Punjab, India). This allowed ample movement of the
      flap and also permitted a V-Y closure of the donor site. The flap also received
      additional blood supply from the ipsilateral superior auricular artery.

PMID- 20692215
TI  - Rolling of the barrels--a flaming tradition in Ottery St Mary, Devon.

PMID- 20692216
TI  - Safety of fat grafting in secondary breast reconstruction after cancer.
AB  - BACKGROUND: Fat grafting is largely used to correct soft-tissue defects in any
      region of the human body. This study analysed its safety when the technique is
      used to correct defects after breast-cancer reconstruction. METHODS: A total of
      158 patients who underwent 194 breast fat grafting procedures were analysed.
      Almost all patients (98%) had a personal history of breast cancer: conservative
      surgery or mastectomy with breast reconstruction. In all cases, fat grafting was
      performed according to the Coleman's technique by a single surgeon. RESULTS:
      Immediate complications included liponecrosis and infection in seven cases (3.6%)
      that required only daily dressings and oral antibiotics administration. In cases
      of fat grafting after conservative surgery, only four patients (5.9%) showed
      minor alterations in the postoperative mammograms, consisting of the appearance
      of benign images. CONCLUSION: Breast fat grafting can be a good solution to
      repair defects after breast-cancer treatment and reconstruction, and can reduce
      the indication for more extensive surgeries such as myocutaneous flaps.
      Postoperative complication rates are very low and there is little alteration in
      follow-up mammograms. Two points remain unclear--how much of the fat is absorbed
      after grafting and the potential risk of local 'dormant' tumour cells being
      stimulated to induce a local recurrence.

PMID- 20692217
TI  - Pediatric resident perceptions of family-friendly benefits.
AB  - OBJECTIVE: The aim of this study was to examine the importance of family-friendly
      features in residency program selection, benefits offered to and used by
      residents, and importance of benefits in future job selection. METHODS: A survey
      of a random, national sample of 1000 graduating pediatric residents in 2008 was
      mailed and e-mailed. RESULTS: Survey response rate for graduating resident
      respondents was 59%. Among the respondents, 76% were women. Thirty-seven percent
      of men and 32% of women were parents. Residents with children were more likely
      than residents without children to rate family-friendly characteristics as very
      important in their residency selection (P < .05). Many residents reported that
      their programs offered maternity leave (88%), paternity leave (59%), individual
      flexibility with schedule (63%), and lactation rooms (55%), but fewer reported on
      site child care (24%), care for ill children (19%), and part-time residency
      positions (12%). Among residents reporting availability, 77% of women with
      children used maternity leave and lactation rooms. Few held part-time residency
      positions (2%), but many expressed interest (23% of women with children). The
      majority of residents with and without children reported that flexibility with
      schedule was important in their future job selection. Most women with children
      (71%) and many women without children (52%) considered part-time work to be very
      important in their job selection. CONCLUSIONS: Family-friendly benefits are
      important to residents, particularly those with children. The data provides a
      benchmark for the availability and use of family-friendly features at pediatric
      training programs. The data also shows that many residents are unaware if
      benefits are offered, which suggests a need to make available benefits more
      transparent to residents.

PMID- 20692218
TI  - Hamatum osteoblastoma.
AB  - We report the case of an osteoblastoma of the hamate bone that was successfully
      treated by curettage. This tumor is very rare in a carpal bone and only nine
      cases have been reported in the literature. Pathological examination is mandatory
      before treatment due to the lack of distinctive clinical and radiological
      features. Osteoblastomas are benign, but potentially aggressive bone tumors.
      Treatment of the lesion may either be a conservative "intralesional resection" or
      radical "wide en bloc resection". The latter option, which has non-negligible
      functional consequences in the wrist, should be reserved for recurrence after
      curettage but may also be considered a primary immediate alternative for
      aggressive forms.

PMID- 20692219
TI  - WHO Informal Consultation on standardization and evaluation of BCG vaccines
      Geneva, Switzerland 22-23 September 2009.
AB  - The current World Health Organization Requirements for BCG vaccine are in need of
      revision to address the diversity of sub-strains used for production, potential
      improvements of quality control assays for lot release, and the establishment of
      sub-strain specific Reference Reagents. A consultation meeting was organized to
      discuss issues regarding the standardization and evaluation of BCG vaccines in
      the forum of regulators, BCG vaccine manufacturers, developers of selected new
      live tuberculosis (TB) vaccines and researchers. The development of new
      recombinant BCG and live attenuated TB vaccines and the characterisation of
      different BCG sub-strains using state-of-the-art technologies were also reviewed.
      The objective of the meeting was to revise and update the current recommendations
      focused on the scope, terminology, manufacturing issues, and the incorporation of
      new reference reagents and new quality control tests.

PMID- 20692220
TI  - Factors affecting compliance with measles vaccination in Lao PDR.
AB  - In line with WHO objectives, the Lao Government is committed to eliminate measles
      by 2012. Yet from 1992 to 2007, the annual incidence of measles remained high
      while the vaccination coverage showed a wide diversity across provinces. A
      descriptive study was performed to determine factors affecting compliance with
      vaccination against measles, which included qualitative and quantitative
      components. The qualitative study used a convenience sample of 13 persons in
      charge of the vaccination program, consisting of officials from different levels
      of the health care structure and members of vaccination teams. The quantitative
      study performed on the target population consisted of a matched, case-control
      survey conducted on a stratified random sample of parents of children aged 9-23
      months. Overall, 584 individuals (292 cases and 292 controls) were interviewed in
      the three provinces selected because of low vaccination coverage. On the
      provision of services side (supply), the main problems identified were a lack of
      vaccine supply and diluent, a difficulty in maintaining the cold chain, a lack of
      availability and competence among health workers, a lack of coordination and a
      limited capacity to assess needs and make coherent decisions. In the side of the
      consumer (demand), major obstacles identified were poor knowledge about measles
      immunization and difficulties in accessing vaccination centers because of
      distance and cost. In multivariate analysis, a low education level of the father
      was a factor of non-immunization while the factors of good compliance were high
      incomes, spacing of pregnancies, a feeling that children must be vaccinated,
      knowledge about immunization age, presenting oneself to the hospital rather than
      expecting the mobile vaccination teams and last, immunization of other family
      members or friends' children. The main factors affecting the compliance with
      vaccination against measles in Laos involve both the supply side and the demand
      side. Obtaining an effective coverage requires upgrading and training the
      Expanded Programme on Immunization (EPI) staff and a reinforcement of health
      education for target populations in all provinces.

PMID- 20692221
TI  - A high-throughput method for quantification of glycoprotein sialylation.
AB  - Sialic acid can improve qualities of therapeutic glycoproteins such as
      circulatory half-life, biological activity, and solubility. In production of
      therapeutic glycoproteins, a high-throughput method is required for process
      monitoring and optimization to ensure consistent and optimal sialic acid content.
      Current methods for quantifying sialic acid, however, require chromatographic
      separation that is time-consuming and cannot rapidly analyze many samples in
      parallel. Here we present a novel high-throughput method for quantifying
      glycoprotein sialylation. Using chemical reduction, enzymatic release of sialic
      acid, and chemical derivatization of the sialic acid, the method can accurately,
      rapidly (15 min), and specifically analyze many samples in parallel. It requires
      only 45 MUl of sample and has a quantitation limit of 2 MUM sialic acid. It has
      also been validated for monitoring sialylation of recombinant interferon gamma
      (IFN-gamma) produced in Chinese hamster ovary (CHO) cell culture. This method is
      useful for various applications in upstream and downstream bioprocesses.

PMID- 20692222
TI  - A high-throughput colorimetric assay to characterize the enzyme kinetic and
      cellular activity of spermidine/spermine N1-acetyltransferase 1.
AB  - Spermidine/spermine N(1)-acetyltransferase 1 (SSAT1) is a key enzyme that
      catalyzes the catabolism of polyamines. SSAT1 is a very important enzyme because
      it not only maintains the homeostasis of polyamines but also is involved in many
      physiological and pathological events. As such, a rapid assay of SSAT1 activity
      is valuable in drug screening and clinical diagnostics. Here, we report a novel
      colorimetric assay for monitoring SSAT1 activity in zebrafish (zSSAT1). In
      comparison with the available SSAT1 assays, this new method is cost-effective and
      simple. The optimal zSSAT1 activity was obtained below 55 degrees C in a mild
      alkaline environment. The K(m) values of zSSAT1 for spermidine and spermine are
      55 and 182 MUM, respectively, whereas putrescine is not a good substrate for
      zSSAT1. In addition to enzyme kinetic studies, the colorimetric assay was also
      used to detect the cellular activity of SSAT1. Thus, the current method is a
      reliable assay for determining SSAT1 activity with many potential applications in
      medical biology.

PMID- 20692223
TI  - Autodisplay of 60-kDa Ro/SS-A antigen and development of a surface display enzyme
      linked immunosorbent assay for systemic lupus erythematosus patient sera
      screening.
AB  - Enzyme-linked immunosorbent assay (ELISA) is a common tool to test human sera on
      an antibody reaction against a specific antigen. The 60-kDa Ro/SS-A antigen for
      autoantibodies can be found in sera from systemic lupus erythematosus (SLE)
      patients. As in the case of 60-kDa Ro/SS-A, antigens used in ELISAs are
      recombinantly expressed in Escherichia coli and time-consuming purification steps
      are needed to get the proteins. To avoid these disadvantages, 60-kDa Ro/SS-A was
      expressed on the surface of E. coli using autodisplay, an efficient surface
      display system. Cells displaying 60-kDa Ro/SS-A on the surface were applied as an
      antigen source instead of the purified antigen. In total, 39 patients and 30
      control sera were screened on a 60-kDa Ro/SS-A antibody reaction. To eliminate
      antibodies against native E. coli, human sera were preabsorbed with E. coli cells
      prior to the assay. The new ELISA protocol (surface display ELISA [SD-ELISA])
      using E. coli with autodisplayed 60-kDa Ro/SS-A showed a sensitivity of 86.67%
      and a specificity of 83.33% by a cutoff value of 0.28. Our results show that
      autodisplay provides simple, rapid, and cheap access to human antigens for an
      ELISA to screen human sera against specific antibody reactions.

PMID- 20692224
TI  - Subunit composition of Rhodothermus marinus respiratory complex I.
AB  - The basic structural characterization of complex I is still not trivial due to
      its complexity, not only in the number of its protein constituents but especially
      because of the different properties of the several subunits. Bacterial complex I
      generally contains 14 subunits: 7 hydrophilic proteins located in the peripheral
      arm and 7 hydrophobic proteins present in the membrane arm. It is the
      identification of the hydrophobic proteins that makes the characterization of
      complex I, and of membrane proteins in general, very difficult. In this article,
      we report the identification of the subunits of complex I from Rhodothermus
      marinus. The original approach, presented here, combined several protein and
      peptides separation strategies (different reversed phase materials, high
      performance liquid chromatography, and gel electrophoresis) with different
      identification methods (electrospray ionization-tandem mass spectrometry, matrix
      assisted laser desorption/ionization-time-of-flight mass spectrometry, and Edman
      degradation analysis) and represents a step forward in the characterization of
      membrane proteins that studies are still technically highly challenging. The
      combination of the different methodologies allowed the identification of complex
      I canonical subunits and also a possible novel subunit, namely a pterin-4alpha
      carbinolamine dehydratase (PCD). This was the first time that a PCD was suggested
      to be part of complex I, and its possible regulatory role is discussed.

PMID- 20692225
TI  - Corruption of phage display libraries by target-unrelated clones: diagnosis and
      countermeasures.
AB  - Phage display is used to discover peptides or proteins with a desired target
      property-most often, affinity for a target selector molecule. Libraries of phage
      clones displaying diverse surface peptides are subject to a selection process
      designed to enrich for the target behavior and subsequently propagated to restore
      phage numbers. A recurrent problem is enrichment of clones, called target
      unrelated phages or peptides (TUPs), that lack the target behavior. Many TUPs are
      propagation related; they have mutations conferring a growth advantage and are
      enriched during the propagations accompanying selection. Unlike other filamentous
      phage libraries, fd-tet-based libraries are relatively resistant to propagation
      related TUP corruption. Their minus-strand origin is disrupted by a large
      cassette that simultaneously confers resistance to tetracycline and imposes a
      rate-limiting growth defect that cannot be bypassed with simple mutations.
      Nonetheless, a new type of propagation-related TUP emerged in the output of in
      vivo selections from an fd-tet library. The founding clone had a complex
      rearrangement that restored the minus-strand origin while retaining tetracycline
      resistance. The rearrangement involved two recombination events, one with a
      contaminant having a wild-type minus-strand origin. The founder's infectivity
      advantage spread by simple recombination to clones displaying different peptides.
      We propose measures for minimizing TUP corruption.

PMID- 20692226
TI  - Spectrophotometric quantification of horseradish peroxidase with o
      phenylenediamine.
AB  - The assay conditions for the spectrophotometric quantification of horseradish
      peroxidase (HRP) with the chromogenic substrate o-phenylenediamine (OPD) at 25
      degrees C in the presence of hydrogen peroxide (H(2)O(2)) were optimized. With
      [OPD](0)=3.14 mM and [H(2)O(2)](0)=80 MUM at pH 7.2, the initial formation of
      only one of the possible reaction products and intermediates, 2,3
      diaminophenazine (DAP, lambda(max)=417 nm), was observed. The rate of DAP
      formation during the first 30 min of reaction was followed spectrophotometrically
      and found to linearly depend on the HRP concentration between 5 and 45 pM under
      the conditions used.

PMID- 20692227
TI  - Catalytic properties and crystal structure of quinoprotein aldose sugar
      dehydrogenase from hyperthermophilic archaeon Pyrobaculum aerophilum.
AB  - We identified a gene encoding a soluble quinoprotein glucose dehydrogenase
      homologue in the hyperthermophilic archaeon Pyrobaculum aerophilum. The gene was
      overexpressed in Escherichia coli, after which its product was purified and
      characterized. The enzyme was extremely thermostable, and the activity of the
      pyrroloquinoline quinone (PQQ)-bound holoenzyme was not lost after incubation at
      100 degrees C for 10 min. The crystal structure of the enzyme was determined in
      both the apoform and as the PQQ-bound holoenzyme. The overall fold of the P.
      aerophilum enzyme showed significant similarity to that of soluble quinoprotein
      aldose sugar dehydrogenase (Asd) from E. coli. However, clear topological
      differences were observed in the two long loops around the PQQ-binding sites of
      the two enzymes. Structural comparison revealed that the hyperthermostability of
      the P. aerophilum enzyme is likely attributable to the presence of an extensive
      aromatic pair network located around a beta-sheet involving N- and C-terminal
      beta-strands.

PMID- 20692228
TI  - SelK is a novel ER stress-regulated protein and protects HepG2 cells from ER
      stress agent-induced apoptosis.
AB  - Selenoprotein K (SelK), an endoplasmic reticulum (ER) resident protein, its
      biological function has been less-well studied. To investigate the role of SelK
      in the ER stress response, effects of SelK gene silence and ER stress agents on
      expression of SelK and cell apoptosis in HepG2 cells were studied. The results
      showed that SelK was regulated by ER stress agents, Tunicamycin (Tm) and beta
      Mercaptoethanol (beta-ME), in HepG2 cells. Moreover, the SelK gene silence by RNA
      interference could significantly aggravate HepG2 cell death and apoptosis induced
      by the ER stress agents. These results suggest that SelK is an ER stress
      regulated protein and plays an important role in protecting HepG2 cells from ER
      stress agent-induced apoptosis.

PMID- 20692229
TI  - alpha-Hemolysin pore formation into a supported phospholipid bilayer using cell
      free expression.
AB  - Cell-free protein synthesis is becoming a serious alternative to cell-based
      protein expression. Cell-free systems can deliver large amounts of cytoplasmic
      recombinant proteins after a few hours of incubation. Recent studies have shown
      that membrane proteins can be also expressed in cell-free reactions and directly
      inserted into phospholipid membranes. In this work, we present a quantitative
      method to study in real time the concurrent cell-free expression and insertion of
      membrane proteins into phospholipid bilayers. The pore-forming protein alpha
      hemolysin, fused to the reporter protein eGFP, was used as a model of membrane
      protein. Cell-free expression of the toxin in solution and inside large synthetic
      phospholipid vesicles was measured by fluorometry and fluorescence microscopy
      respectively. A quartz crystal microbalance with dissipation was used to
      characterize the interaction of the protein with a supported phospholipid
      bilayer. The cell-free reaction was directly incubated onto the bilayer inside
      the microbalance chamber while the frequency and the dissipation signals were
      monitored. The presence of pores in the phospholipid bilayer was confirmed by
      atomic force microscopy. A model is presented which describes the kinetics of
      adsorption of the expressed protein on the phospholipid bilayer. The combination
      of cell-free expression, fluorescence microscopy and quartz crystal microbalance
      dissipation is a new quantitative approach to study the interaction of membrane
      proteins with phospholipid bilayers.

PMID- 20692230
TI  - A biophysical glance at the outer surface of the membrane transporter SGLT1.
AB  - Proteins mediating the transport of solutes across the cell membrane control the
      intracellular conditions in which life can occur. Because of the particular
      arrangement of spanning a lipid bilayer and the many conformations required for
      their function, transport proteins pose significant obstacles for the
      investigation of their structure-function relation. Crystallographic studies, if
      available, define the transmembrane segments in a "frozen" state and do not
      provide information on the dynamics of the extramembranous loops, which are
      similarly evolutionary conserved and thus as functionally important as the other
      parts of the protein. The current review presents biophysical methods that can
      shed light on the dynamics of transporters in the membrane. The techniques that
      are presented in some detail are single-molecule recognition atomic force
      microscopy and tryptophan scanning, which can report on the positioning of the
      loops and on conformational changes at the outer surface. Studies on a variety of
      symporters are discussed, which use gradients of sodium or protons as energy
      source to translocate (mainly organic) solutes against their concentration
      gradients into or out of the cells. Primarily, investigations of the sodium
      glucose cotransporter SGLT1 are used as examples for this biophysical approach to
      understand transporter function.

PMID- 20692231
TI  - Lipid chain branching at the iso- and anteiso-positions in complex Chlamydia
      membranes: a molecular dynamics study.
AB  - Membranes in the intracellular eubacterial parasite Chlamydia trachomatis consist
      of the elementary body (EB) and reticular body (RB), and contain methyl branches
      at the iso- and anteiso-positions for some phospholipid chains. Acyl chain
      branching is the focus of this study. Molecular dynamics simulations were used to
      study bilayers of 1-13-methylpentadecanoyl-2-palmitoyl-phosphatidylcholine (13
      MpPPC), 1-14-methylpentadecanoyl-2-palmitoyl-phosphatidylcholine (14-MpPPC), and
      diphytanoylphosphatidylcholine (DPhPC). These three membranes were simulated at
      323K and simulations of DPhPC at 298K were also performed for better comparison
      to existing experimental data. Two simulations of representative EB and RB
      membranes of C. trachomatis composed of nine different lipid components were
      performed at 310.15K, to accurately reflect compositions determined by experiment
      and physiological conditions. Based on nearly 0.5MUs of simulation data, we
      report that branching increases average lipid surface area, area elastic moduli,
      and lipid axial relaxation times, while decreasing lipid chain order. Branching
      also has a distinct effect on electron density profiles. Due to their high
      cholesterol concentrations, the EB and RB membranes were found to have relatively
      high area elastic moduli, which may have important biological implications.

PMID- 20692232
TI  - IGF-1 receptor inhibition by picropodophyllin in medulloblastoma.
AB  - The insulin-like growth factor-1 receptor (Igf1r) is a multifunctional membrane
      associated tyrosine kinase associated with regulation of transformation,
      proliferation, differentiation and apoptosis. Increased IGF pathway activity has
      been reported in human and murine medulloblastoma. Tumors from our genetically
      engineered medulloblastoma mouse model over-express Igf1r, and thus this mouse
      model is a good platform with which to study the role of Igf1r in tumor
      progression. We hypothesize that inhibition of IGF pathway in medulloblastoma can
      slow or inhibit tumor growth and metastasis. To test our hypothesis, we tested
      the role of IGF in tumor growth in vitro by treatment with the tyrosine kinase
      small molecule inhibitor, picropodophyllin (PPP), which strongly inhibits the IGF
      pathway. Our results demonstrate that PPP-mediated downregulation of the IGF
      pathway inhibits mouse tumor cell growth and induces apoptotic cell death in
      vitro in primary medulloblastoma cultures that are most reflective of tumor cell
      behavior in vivo.

PMID- 20692233
TI  - Tissue and plasma globotriaosylsphingosine could be a biomarker for assessing
      enzyme replacement therapy for Fabry disease.
AB  - Fabry disease is a genetic disease caused by a deficiency of alpha-galactosidase
      A (GLA), which leads to systemic accumulation of glycolipids, predominantly
      globotriaosylceramide (Gb3). With the introduction and spread of enzyme
      replacement therapy (ERT) with recombinant GLAs for this disease, a useful
      biomarker for assessing the response to ERT is strongly required. We measured the
      tissue level of lyso-globotriaosylsphingosine (lyso-Gb3) in Fabry mice by means
      of high performance liquid chromatography, and compared it with the Gb3 level.
      The results revealed a marked increase in the lyso-Gb3 level in most tissues of
      Fabry mice, and which decreased after the administration of a recombinant GLA as
      in the case of Gb3, which is usually used as a biomarker of Fabry disease. The
      response was more impressive for lyso-Gb3 compared with for Gb3, especially in
      kidney tissues, in which a defect significantly influences the morbidity and
      mortality in patients with this disease. The plasma level of lyso-Gb3 also
      decreased after the injection of the enzyme, and it was well related to the
      degradation of tissue lyso-Gb3. Thus, lyso-Gb3 is expected to be a useful new
      biomarker for assessing the response to ERT for Fabry disease.

PMID- 20692234
TI  - Hypoxia induces adipogenic differentitation of myoblastic cell lines.
AB  - Muscle atrophy usually accompanies fat accumulation in the muscle. In such
      atrophic conditions as back muscles of kyphotic spine and the rotator cuff
      muscles with torn tendons, blood flow might be diminished. It is known that
      hypoxia causes trans-differentiation of mesenchymal stem cells derived from bone
      marrow into adipocytes. However, it has not been elucidated yet if hypoxia turned
      myoblasts into adipocytes. We investigated adipogenesis in C2C12 and G8 murine
      myogenic cell line treated by hypoxia. Cells were also treated with the cocktail
      of insulin, dexamethasone and IBMX (MDI), which has been known to inhibit Wnt
      signaling and promote adipogenesis. Adipogenic differentiation was seen in both
      hypoxia and MDI. Adipogenic marker gene expression was assessed in C2C12.
      CCAAT/enhancer-binding protein (C/EBP) beta, alpha and peroxisome proliferator
      activating receptor (PPAR) gamma were increased by both hypoxia and MDI. The
      expression profile of Wnt10b was different between hypoxia and MDI. The mechanism
      for adipogenesis of myoblasts in hypoxia might be regulated by different
      mechanism than the modification of Wnt signaling.

PMID- 20692235
TI  - Deficiency of autotaxin/lysophospholipase D results in head cavity formation in
      mouse embryos through the LPA receptor-Rho-ROCK pathway.
AB  - Autotaxin, encoded by the Enpp2 gene, generates lysophosphatidic acid (LPA)
      extracellularly, eliciting various cellular responses through specific LPA
      receptors. Previous studies have revealed that Enpp2(-/-) mice die at E9.5 owing
      to angiogenic defects in the yolk sac. Moreover, Enpp2(-/-) embryos show growth
      retardation, allantois malformation, no axial turning, and head cavity formation.
      We have also demonstrated that lysosome biogenesis is impaired in yolk sac
      visceral endoderm cells of Enpp2(-/-) embryos as a result of the downregulation
      of the Rho-ROCK (Rho-associated coiled-coil containing protein kinase)-LIM kinase
      pathway. In this study, we examine what signaling defect(s) is responsible for
      head cavity formation and yolk sac angiogenic defects. By using a whole embryo
      culture system, we show that 10 MUM Ki16425, an antagonist for the LPA receptors,
      induces head cavity formation and yolk sac angiogenic defects in wild-type
      embryos. Moreover, 1 MUM Ki16425 induces both phenotypes in Enpp2 heterozygous
      embryos at significantly higher incidence than in wild-type embryos, suggesting
      an interaction between autotaxin and LPA receptor signaling. Furthermore, we show
      that inhibition of the Rho-ROCK pathway induces head cavity formation, whereas
      multiple pathways are involved in yolk sac angiogenic defects. These results
      reveal the signal transduction defects that underlie the abnormalities in Enpp2(
      /-) embryos.

PMID- 20692236
TI  - A novel preclinical rodent model of collagenase-induced germinal
      matrix/intraventricular hemorrhage.
AB  - Germinal matrix/intraventricular hemorrhage (GMH/IVH) is a complication that
      arises in premature infants associated with neurological sequelae. Greater
      understanding of GMH/IVH is needed to develop therapies, a goal that depends on
      the existence of appropriate animal models. Towards this goal, we aimed to
      develop a rodent model of GMH/IVH based on collagenase-induced hemorrhage that
      exhibits histological and neurological consequences similar to that seen in
      patients. Male 6-day-old rats were placed on a warming pad and anesthetized with
      halothane/nitrous oxide delivered by face mask. Uni- or bilateral periventricular
      injections of 2-MUl collagenase (2.0 U) were performed freehand with a needle
      inserted percutaneously. Sham rats were infused with saline. Early neonatal
      development, long-term motor and cognitive performances and alterations in brain
      volume were assessed. Collagenase-based GMH/IVH negatively affected ambulation,
      surface righting and negative geotaxis outcomes more evidently in bilaterally
      infused rats, which also presented an early decrease in brain volume, as assessed
      by the Cavalieri method. In adult animals, a unilateral collagenase infusion
      produced no significant alteration on forepaw preference. Only bilaterally
      infused rats presented an impairment of object recognition memory and locomotor
      deficit. Nevertheless, histological evaluation also demonstrated a persistent
      brain volume reduction in bilaterally infused rats. Our study provides a
      pioneering animal model of collagenase-based GMH/IVH, which can be used to
      evaluate preventive strategies and potential therapeutic interventions for this
      disorder.

PMID- 20692237
TI  - Postnatal period of caffeine treatment and time of testing modulate the effect of
      acute caffeine on cortical epileptic afterdischarges in rats.
AB  - Recently, we have found that postnatal caffeine treatment results in a dose
      dependent pro- or anticonvulsant effect during brain maturation which effect is
      transient and disappears in adult rats. The aim of the present study was to
      determine whether the developmental period of chronic caffeine treatment and the
      age of testing are crucial for the effects of acute caffeine on cortical
      epileptic afterdischarges (ADs) in rats. Rhythmic electrical stimulation of
      somatosensory cortex was applied to elicit EEG and motor phenomena in 18- and 25
      day-old rats, respectively. Acute injection of caffeine (10 and 20mg/kg s.c.)
      decreased the threshold for stimulation-bound movements in both age groups while
      it increased the thresholds for spike-and-wave ADs and clonic seizures
      accompanying them at P25. Acute caffeine had a similar effect on thresholds for
      spike-and-wave ADs and clonic seizures in 25-day-old rats exposed to the
      methylxanthine at P7-P11 and P13-17, respectively. Though caffeine administration
      per se did not change the duration of ADs at P18 it produced either a pro- or
      anticonvulsant effect after postnatal treatment (P7-P11 and P13-P17,
      respectively). However, acute caffeine exerted a prolongation of ADs at P25 which
      effect was alleviated after both developmental periods of treatment. Taken
      together, acute caffeine effects on cortical epileptic ADs in rats can be
      modulated by the postnatal period of treatment and age of testing.

PMID- 20692238
TI  - The c-Jun N-terminal kinase inhibitor SP600125 is neuroprotective in amygdala
      kindled rats.
AB  - c-Jun N-terminal kinase (JNK) is implicated in cell death in neurodegenerative
      disorders and has been taken as a critical point between the physiological and
      pathological status. JNK specific inhibitor SP600125 has been found to have a
      protective effect against transient brain ischemia/reperfusion-induced neuronal
      death in rat hippocampal CA1 region. Former studies have shown the relation
      between JNK phosphorylation and neuronal damage in models of brain ischemia or in
      chemically or acute electrically kindled animal in which the stimulus-induced JNK
      phosphorylation was temporary or transient. In this study, the effect of repeated
      activation of JNK was examined in the amygdala kindled rats, under or without
      intraventrical infusion of SP600125, compared with the sham control. JNK
      phosphorylation was detected by Western blot and immunofluorescent staining in
      hippocampal extracts and in slices respectively. Nissl staining was performed to
      detect the neuronal defect. We found that the level of JNK phosphorylation (46KD)
      in the hippocampus increased in the amygdala kindled rats, whereas such JNK
      phosphorylation could be inhibited by SP600125. Expression of total JNK in the
      hippocampus remained unchanged in kindled rats compared with the sham control,
      and was not affected by SP600125. Neuronal defect was marked in the kindling
      group and in the vehicle DMSO group, and was alleviated under the administration
      of SP600125. These findings suggest that JNK phosphorylation is involved in the
      process of hippocampal sclerosis in the mesial temporal lobe epilepsy (TLE). JNK
      signaling pathway may be a new target to interfere with the development of
      hippocampal sclerosis in the temporal lobe epilepsy. The JNK inhibitor SP600125
      can show a protective effect on hippocampal neurons in TLE by inhibiting JNK
      activation.

PMID- 20692239
TI  - Cytokine signaling in the human brain capillary endothelial cell line hCMEC/D3.
AB  - Brain microvascular endothelial cells are part of the blood-brain barrier and
      participate actively in immunological processes including cytokine-mediated
      inflammatory reactions. Using the human brain capillary endothelial cell line
      hCMEC/D3, activation of JAK/STAT signaling pathways were studied in response to
      stimulation by cytokines. The phenotype of hCMEC/D3 cells was confirmed by flow
      cytometry analysis of cell adhesion factors (cluster of differentiation molecules
      CD31 and CD34) and the von Willebrand factor endothelial marker was detected by
      immunofluorescence. Strong STAT1, STAT6 and STAT3 activation was observed in
      response to interferon-gamma (IFN-gamma), interleukin 4 (IL-4) and interleukin 6
      (IL-6), respectively. Nuclear translocation of phosphorylated STAT proteins was
      visualized by confocal microscopy. Treatment of hCMEC/D3 cells with IFN-gamma
      resulted in interferon-induced upregulation of major histocompatibility complex
      (MHC) class I within 48h. Interferon-alpha (IFN-alpha) did not activate STAT1 or
      STAT3 nor did it induce MHC class I upregulation. Therefore, hCMEC/D3 cells were
      judged to be non-responsive to IFN-alpha. We also observed that hCMEC/D3 cells
      exhibit functional expression of alternative cytokine signal transduction
      pathways (i.e. TNF-alpha mediated activation of NF-kappaB). Together these
      results indicate that human blood-brain barrier hCMEC/D3 cells are responsive
      towards stimulation with various cytokines. We conclude that this unique cell
      line can be used to explore in vitro human blood-brain barrier functionality
      under proinflammatory conditions.

PMID- 20692240
TI  - Role of p75NTR in NMDAR-mediated excitotoxic brain injury in neonatal mice.
AB  - BACKGROUND: Perinatal brain injury in preterm infants is a major cause of
      neurological handicap. The role of the neurotrophin receptor p75 (p75(NTR)) in
      the pathogenesis and repair of neonatal excitotoxic brain injury is unknown.
      Depending on a complex interplay of neurotrophin signalling, p75(NTR) can, in
      addition to its trophic function, also induce apoptosis. HYPOTHESIS: We
      hypothesised that excitotoxicity increases p75(NTR) expression and p75(NTR)
      knockout (KO) mice have a significantly smaller lesion size upon excitotoxicity
      as compared to wild-type (WT) mice. METHODS: We used an established animal model
      of neonatal excitotoxic brain injury mimicking several key aspects of human
      preterm brain damage. We subjected five-day-old WT and KO mice to excitotoxic
      injury by means of a single intracranial ibotenate injection (N-methyl-D
      aspartate receptor agonist, NMDAR) into one brain hemisphere. Lesion size, number
      of activated caspase-3- and apoptosis-inducing factor (AIF)-positive cells were
      determined as outcome parameters. Gender analyses were taken into account
      retrospectively. RESULTS: NMDAR-mediated excitotoxicity induced an upregulation
      of p75(NTR) expression in the peri-lesion area. Lesion size was significantly
      increased in female KO as compared to male KO animals. Knockout of p75(NTR)
      reduced the number of activated caspase-3 but not AIF-positive cells after NMDAR
      mediated excitotoxic injury independently of gender. CONCLUSION: Since NMDAR
      mediated excitotoxic brain injury induced p75(NTR) expression and caspase-3
      activated apoptosis in p75(NTR) KO animals was decreased, we conclude that
      activation of p75(NTR) contributes to NMDAR-mediated apoptosis in the neonatal
      brain. An increase in lesion size in female animals after excitotoxic brain
      injury suggests that in females p75(NTR) seems to play a dual role.

PMID- 20692241
TI  - Cross-modal and compensatory plasticity in adult deafened cats: a longitudinal
      PET study.
AB  - Although much is known about the cerebral neural plasticity that occurs after
      deafness, it is unclear how much time is required for its development or what
      other cortical changes may consequently occur. This study provides a longitudinal
      assessment of cerebral cortical neural plasticity, as manifested in adult
      deafened cats. A total of 5 male cats were subjected to whole cortex analysis of
      glucose metabolic activity via 2-deoxy-2[(18)F] fluoro-D-glucose (FDG) micro
      positron emission tomography (PET). The imaging was performed at the baseline
      state of normal hearing and then at 4, 9, 24, and 33 months after the induction
      of deafness. We compared glucose metabolism between the normal hearing state and
      each deafened state by using voxel-based statistical analysis (P<0.005).
      Significant changes were observed in the primary auditory (A1) and primary visual
      (V1) cortices. A bilateral metabolic decrease was observed in A1 areas and in
      temporal auditory fields, the extent of which was significantly increased at
      Month 9. Then it was declined at Month 24. And finally it was disappeared by
      Month 33. Auditory cortical plasticity subsequent to deafness was thus
      demonstrated. Furthermore, a significant metabolic upsurge occurred in bilateral
      occipital areas at Month 33. This increase, involving bilateral occipital and
      thalamic areas of V1, suggests compensatory hyperactivity of the visual cortex
      after deafness.

PMID- 20692242
TI  - Metabotropic glutamate receptors 1 and 5 differentially regulate bulbar
      dopaminergic cell function.
AB  - Effects of activation of metabotropic glutamatergic receptors (mGluR) were
      investigated in mouse dopaminergic olfactory bulb neurons. After blockage of
      ionotropic receptors, focal application of glutamate or of group I/II mGluR
      agonist t-ACPD resulted in a depolarization, paralleled by an inward current in
      voltage-clamp conditions. The Group I agonist DHPG induced a depolarization,
      which could be largely blocked by mGluR1 antagonists. The DHPG action i) was
      prevented by buffering intracellular Ca(2+) with BAPTA and by a phospholipase C
      inhibitor; ii) was not affected by the block of Ca(2+) entry, and iii) was
      blocked by inhibitors of the Na(+)/Ca(2+) exchanger. These observations were
      interpreted as a mGluR1-mediated intracellular Ca(2+) release, followed by the
      activation of an electrogenic Na(+)/Ca(2+) exchanger. The mGluR5 agonist CHPG
      induced a hyperpolarization of membrane potential, resulting in a decrease of the
      spontaneous firing frequency. CHPG induced i) a decrease in membrane resistance;
      ii) an increase in the action potential repolarization rate, and iii) an increase
      in the amplitude of the afterhyperpolarization. This was interpreted as a mGluR5
      mediated opening of a K(+) conductance. These data suggest that mGluR1 and mGluR5
      play different and non-overlapping roles in the regulation of the excitability of
      bulbar dopaminergic neurons.

PMID- 20692243
TI  - Down-regulated transcriptional level of Ace1 combined with mutations in Ace1 and
      Ace2 of Aphis gossypii are related with omethoate resistance.
AB  - The degree of insecticide resistance, acetylcholinesterase (AChE) activity
      kinetics, AChE gene expression and the cDNA sequence of AChE gene were
      investigated in resistant and relatively susceptible strains of the cotton
      aphids, Aphis gossypii (Glover). The resistant strain (ORR) exhibited 53.28-fold
      resistance to omethoate compared to the relatively susceptible strain (OSS) in
      cotton aphids. AChE activity, V(max) and K(m) were significantly lower in the ORR
      strain than in the OSS strain (0.13-, 0.04- and 0.31-fold, respectively). Based
      on analysis of IC(50) indices, enzyme inhibition experiments showed that AChE
      from the ORR strain was 7.99-, 4.12-, 4.27-, 8.71- and 4.57-fold insensitive to
      inhibition by eserine, omethoate, paraoxon, paraoxon-methyl and malaoxon than the
      OSS strain. Sequence analysis indicated that there were no amino acid
      substitutions in AChEI (Ace1) and AChEII (Ace2) between the OSS and ORR strain.
      However, when compared with the 81-171B strain (GenBank No. AF502081), we
      detected two site mutations (S146N and L532P) in Ace1 with high frequency in both
      the ORR and OSS strains. One conserved mutation (S431F) in Ace2 was also found in
      both strains when compared with the 171B strain (GenBank No. AJ748114).
      Measurements of the levels of gene expression for Ace1 and Ace2 in ORR and OSS,
      as determined by real-time quantitative PCRs, revealed that the relative
      transcription levels of Ace1 and Ace2 were 0.26- and 1.07-fold, respectively, in
      the ORR strain as compared to the OSS strain. These results indicate that the
      altered AChE sensitivity brought about by a decreased transcriptional level of
      Ace1 mRNA and combined with the site mutants in both Ace1 and Ace2 might be
      related to omethoate resistance in cotton aphids.

PMID- 20692244
TI  - A novel anticancer agent, retigeric acid B, displays proliferation inhibition, S
      phase arrest and apoptosis activation in human prostate cancer cells.
AB  - Retigeric acid B (RB), a naturally occurring pentacyclic triterpenic acid, has
      been noted for its antifungal properties in vitro. Here, we observed that RB
      inhibited prostate cancer cell proliferation and induced cell death in a dose
      dependent manner, but exerted very little inhibitory effect on noncancerous
      prostate epithelial cell viability. Treatment of androgen-independent PC-3 cells
      with RB caused a moderate increase in p21(Cip1), and enforced the cell cycle
      arrest in the S phase. A block of S phase was accompanied with decreases in
      cyclin B, and increases in cyclin E and cyclin A proteins and phosphorylated
      retinoblastoma protein (pRb), whereas the expression of cdk2 remained almost
      unchanged in PC-3 cells exposed to RB. Moreover, RB significantly inhibited DNA
      synthesis with a dose-dependent reduction in the incorporation of BrdU into DNA,
      and enhanced apoptosis of PC-3 cells with induction of a higher ratio of Bax/Bcl
      2 proteins, and activation of caspase-3 which, in turn, promoted the cleavage of
      poly (ADP-ribose) polymerase (PARP). However, pretreatment with the pan-caspase
      inhibitor z-VAD-fmk only partially alleviated RB-triggered apoptosis in PC-3
      cells, suggesting the involvement of both caspase-dependent and caspase
      independent pathways. Additionally, treatment of androgen-sensitive LNCaP cells
      with RB led to a reduction in the expression of androgen receptor (AR), and
      subsequently decreased the transactivity of AR. These observations help to
      support the search for promising candidates to treat prostate cancer.

PMID- 20692245
TI  - Insertion/insertion genotype of alpha(2B)-adrenergic receptor gene polymorphism
      is associated with silent myocardial ischemia in patients with type 2 diabetes
      mellitus.
AB  - OBJECTIVES: We investigated whether alpha(2)-adrenergic receptor (AR)
      polymorphisms (alpha(2A)-AR, alpha(2B)-AR and alpha(2C)-AR gene) affected silent
      myocardial ischemia (SMI) in patients with type 2 diabetes mellitus (T2DM).
      DESIGN AND METHODS: Genetic polymorphisms were determined in 321 patients with
      T2DM and coronary artery disease (CAD). Among them, 129 patients experienced
      transient asymptomatic ST-depression during 24-hour ambulatory electrocardiogram
      (SMI group), and the remaining 192 patients who had ambulatory electrocardiogram
      symptom matching angina were categorized as angina group. RESULTS: The genotype
      distribution and allele frequencies of alpha(2B)-AR gene polymorphism (insertion
      [I]/deletion[D]) exhibited significant difference between SMI group and angina
      group (both P < 0.05), with genotype II (34.9%) being higher in SMI group than in
      angina group (19.8%) (P < 0.01). Multivariable logistic regression analysis
      revealed that duration of diabetes and genotype II of alpha(2B)-AR gene
      polymorphism were independently associated with SMI. CONCLUSIONS: Homozygote for
      I allele of alpha(2B)-AR gene polymorphism is associated with SMI in T2DM
      patients with CAD.

PMID- 20692246
TI  - Paraoxonase activity in athletes with depleted iron stores and iron-deficient
      erythropoiesis.
AB  - OBJECTIVE: The aim of this study was to evaluate how conditions that precede
      anaemia (iron store depletion and iron-deficient erythropoiesis) affect human
      serum paraoxonase PON1 activity. DESIGN AND METHODS: Based on haemoglobin,
      transferrin saturation and serum ferritin values 119 athletes were divided into
      three groups: with iron depletion, with deficient erythropoiesis and controls.
      The following parameters were measured: paraoxonase activity towards paraoxon
      (POase) and diazoxon (DZOase), lipid hydroperoxides (LOOH), the pro-oxidant
      antioxidant balance (PAB), red blood cells (RBC) and lipid status. RESULTS:
      Significant differences were found between athletes with different stages of iron
      deficiency and controls with respect to PON 1 activity and oxidative stress
      status parameters (Wilks' Lambda=0.712, F=5.241, p<0.001, eta(2)=0.156). There
      was no significant difference between the PON1 192 Q and R polymorphism
      distribution in the two groups of athletes with different stages of iron
      deficiency and controls (chi(2)=1.086; p=0.896). PON1 activity was positively
      correlated with RBCs, haemoglobin, transferrin saturation (p<0.001) and ferritin
      (p=0.037) and negatively correlated with LOOH (p=0.044) in all three study
      groups. CONCLUSIONS: Deficient erythropoiesis in athletes contributes to impaired
      PON1 activity. In contrast, iron depletion, regardless of increased oxidative
      stress, does not affect PON1 activity.

PMID- 20692247
TI  - Direct transcriptional regulation of Gata4 during early endoderm specification is
      controlled by FoxA2 binding to an intronic enhancer.
AB  - The embryonic endoderm is a multipotent progenitor cell population that gives
      rise to the epithelia of the digestive and respiratory tracts, the liver and the
      pancreas. Among the transcription factors that have been shown to be important
      for endoderm development and gut morphogenesis is GATA4. Despite the important
      role of GATA4 in endoderm development, its transcriptional regulation is not well
      understood. In this study, we identified an intronic enhancer from the mouse
      Gata4 gene that directs expression to the definitive endoderm in the early
      embryo. The activity of this enhancer is initially broad in all endodermal
      progenitors, as demonstrated by fate mapping analysis using the Cre/loxP system,
      but becomes restricted to the dorsal foregut and midgut, and associated organs
      such as dorsal pancreas and stomach. The function of the intronic Gata4 enhancer
      is dependent upon a conserved Forkhead transcription factor-binding site, which
      is bound by recombinant FoxA2 in vitro. These studies identify Gata4 as a direct
      transcriptional target of FoxA2 in the hierarchy of the transcriptional
      regulatory network that controls the development of the definitive endoderm.

PMID- 20692248
TI  - Concomitant requirement for Notch and Jak/Stat signaling during neuro-epithelial
      differentiation in the Drosophila optic lobe.
AB  - The optic lobe forms a prominent compartment of the Drosophila adult brain that
      processes visual input from the compound eye. Neurons of the optic lobe are
      produced during the larval period from two neuroepithelial layers called the
      outer and inner optic anlage (OOA, IOA). In the early larva, the optic anlagen
      grow as epithelia by symmetric cell division. Subsequently, neuroepithelial cells
      (NE) convert into neuroblasts (NB) in a tightly regulated spatio-temporal
      progression that starts at the edges of the epithelia and gradually move towards
      its centers. Neuroblasts divide at a much faster pace in an asymmetric mode,
      producing lineages of neurons that populate the different parts of the optic
      lobe. In this paper we have reconstructed the complex morphogenesis of the optic
      lobe during the larval period, and established a role for the Notch and Jak/Stat
      signaling pathways during the NE-NB conversion. After an early phase of complete
      overlap in the OOA, signaling activities sort out such that Jak/Stat is active in
      the lateral OOA which gives rise to the lamina, and Notch remains in the medial
      cells that form the medulla. During the third instar, a wave front of enhanced
      Notch activity progressing over the OOA from medial to lateral controls the
      gradual NE-NB conversion. Neuroepithelial cells at the medial edge of the OOA,
      shortly prior to becoming neuroblasts, express high levels of Delta, which
      activates the Notch pathway and thereby maintains the OOA in an epithelial state.
      Loss of Notch signaling, as well as Jak/Stat signaling, results in a premature NE
      NB conversion of the OOA, which in turn has severe effects on optic lobe
      patterning. Our findings present the Drosophila optic lobe as a useful model to
      analyze the key signaling mechanisms controlling transitions of progenitor cells
      from symmetric (growth) to asymmetric (differentiative) divisions.

PMID- 20692249
TI  - Allometric growth of the trunk leads to the rostral shift of the pelvic fin in
      teleost fishes.
AB  - The pelvic fin position among teleost fishes has shifted rostrally during
      evolution, resulting in diversification of both behavior and habitat. We explored
      the developmental basis for the rostral shift in pelvic fin position in teleost
      fishes using zebrafish (abdominal pelvic fins) and Nile tilapia (thoracic pelvic
      fins). Cell fate mapping experiments revealed that changes in the distribution of
      lateral plate mesodermal cells accompany the trunk-tail protrusion. Presumptive
      pelvic fin cells are originally located at the body wall adjacent to the anterior
      limit of hoxc10a expression in the spinal cord, and their position shifts
      rostrally as the trunk grows. We then showed that the differences in pelvic fin
      position between zebrafish and Nile tilapia were not due to changes in expression
      or function of gdf11. We also found that hox-independent motoneurons located
      above the pelvic fins innervate into the pelvic musculature. Our results suggest
      that there is a common mechanism among teleosts and tetrapods that controls
      paired appendage positioning via gdf11, but in teleost fishes the position of
      prospective pelvic fin cells on the yolk surface shifts as the trunk grows. In
      addition, teleost motoneurons, which lack lateral motor columns, innervate the
      pelvic fins in a manner independent of the rostral-caudal patterns of hox
      expression in the spinal cord.

PMID- 20692250
TI  - Defective adult oligodendrocyte and Schwann cell development, pigment pattern,
      and craniofacial morphology in puma mutant zebrafish having an alpha tubulin
      mutation.
AB  - The processes of myelination remain incompletely understood but are of profound
      biomedical importance owing to the several dysmyelinating and demyelinating
      disorders known in humans. Here, we analyze the zebrafish puma mutant, isolated
      originally for pigment pattern defects limited to the adult stage. We show that
      puma mutants also have late-arising defects in Schwann cells of the peripheral
      nervous system, locomotor abnormalities, and sex-biased defects in adult
      craniofacial morphology. Using methods of positional cloning, we identify a
      critical genetic interval harboring two alpha tubulin loci, and we identify a
      chemically induced missense mutation in one of these, tubulin alpha 8-like 3a
      (tuba8l3a). We demonstrate tuba8l3a expression in the central nervous system
      (CNS), leading us to search for defects in the development of oligodendrocytes,
      the myelinating cells of the CNS. We find gross reductions in CNS myelin and
      oligodendrocyte numbers in adult puma mutants, and these deficits are apparent
      already during the larval-to-adult transformation. By contrast, analyses of
      embryos and early larvae reveal a normal complement of oligodendrocytes that
      nevertheless fail to localize normal amounts of myelin basic protein (mbp) mRNA
      in cellular processes, and fail to organize these processes as in the wild-type.
      This study identifies the puma mutant as a valuable model for studying
      microtubule-dependent events of myelination, as well as strategies for
      remyelination in the adult.

PMID- 20692252
TI  - Paraxial T-box genes, Tbx6 and Tbx1, are required for cranial chondrogenesis and
      myogenesis.
AB  - We previously reported that Tbx6, a T-box transcription factor, is required for
      the differentiation of ventral body wall muscle and for segment formation and
      somitic muscle differentiation. Here, we show that Tbx6 is also involved, at
      later stages, in cartilage differentiation from the cranial neural crest and head
      muscle development. In Tbx6 knockdown embryos, the cranial neural crest was shown
      to be correctly induced at the border of the neural plate and migrated in a
      slightly delayed manner, but finally reached positions in the pharyngeal arches
      nearly similar to those in the normal embryos as revealed by in situ
      hybridization and the neural crest-transplantation experiments. However, the
      neural crest cells failed to maintain Sox9 expression. Tbx6 knockdown also
      reduced the expression of Tbx1, another T-box gene expressed in more anterior
      paraxial structures. Tbx1 knockdown caused phenotypes milder but similar to those
      of Tbx6 morphants, including reduced formation of head muscles and cartilages,
      and attenuated Sox9 expression. Furthermore, the phenotypes caused by Tbx6
      knockdown were partially rescued by Tbx1 plasmid injection. These results suggest
      that Tbx6 is involved in the cranial cartilage and head muscle development by
      regulating anterior paraxial genes such as Tbx1 and Sox9.

PMID- 20692251
TI  - poky/chuk/ikk1 is required for differentiation of the zebrafish embryonic
      epidermis.
AB  - An epidermis surrounds all vertebrates, forming a water barrier between the
      external environment and the internal space of the organism. In the zebrafish,
      the embryonic epidermis consists of an outer enveloping layer (EVL) and an inner
      basal layer that have distinct embryonic origins. Differentiation of the EVL
      requires the maternal effect gene poky/ikk1 in EVL cells prior to establishment
      of the basal layer. This requirement is transient and maternal Ikk1 is sufficient
      to allow establishment of the EVL and formation of normal skin in adults. Similar
      to the requirement for Ikk1 in mouse epidermis, EVL cells in poky mutants fail to
      exit the cell cycle or express specific markers of differentiation. In spite of
      the similarity in phenotype, the molecular requirement for Ikk1 is different
      between mouse and zebrafish. Unlike the mouse, EVL differentiation requires
      functioning Poky/Ikk1 kinase activity but does not require the HLH domain.
      Previous work suggested that the EVL was a transient embryonic structure, and
      that maturation of the epidermis required replacement of the EVL with cells from
      the basal layer. We show here that the EVL is not lost during embryogenesis but
      persists to larval stages. Our results show that while the requirement for
      poky/ikk1 is conserved, the differences in molecular activity indicate that
      diversification of an epithelial differentiation program has allowed at least two
      developmental modes of establishing a multilayered epidermis in vertebrates.

PMID- 20692253
TI  - Oxidized low-density lipoprotein (oxLDL) induces cell death in neuroblastoma and
      survival autophagy in schwannoma cells.
AB  - Oxidized low-density lipoprotein (oxLDL) induces apoptosis or autophagy in
      dependence on the cell type. We here investigated the effect of oxLDL on the B104
      neuroblastoma and RN22 schwannoma cells being popular in neuroscience research.
      Cells were cultivated with and without oxLDL. To generate oxLDL, we added 50
      MUg/ml nLDL and 50 MUM CuSO(4) into the culture medium. After a 24-h-long
      treatment, oxLDL was detectable in media from both cell culture types and its
      concentration was approximately 16 MUg/ml. In the oxLDL-treated B104
      neuroblastoma cell cultures 75% cells died after the 24-h exposure. The intact
      cells showed impaired mitochondria at the ultrastructural level. Western blot
      analysis revealed the increased expression of AIF 57 kDa (AIF(57)) protein, as a
      sign of caspase-independent cell death. In RN22 schwannoma cell cultures, oxLDL
      did not have any effect on cleaved caspase-3 and AIF(57) protein levels
      indicating absence of cell death. Treated RN22 schwannoma cells underwent
      survival autophagy by forming conspicuous autophagosomes and by processing LC3-I
      into LC3-II protein. Collectively, oxLDL induces AIF-dependent cell death in B104
      neuroblastoma cells whereas in RN22 schwannoma cells enhanced signs of survival
      autophagy are noted.

PMID- 20692254
TI  - Toll-like receptor 3 mediates expression of clusterin/apolipoprotein J in
      vascular smooth muscle cells stimulated with RNA released from necrotic cells.
AB  - Clusterin/Apolipoprotein J is a protein that is upregulated in a broad spectrum
      of diverse pathological processes. The predominant form is a secreted
      glycoprotein (sCLU) with cytoprotective and anti-inflammatory properties which
      shows enhanced expression in vascular smooth muscle cells (VSMC) following aortic
      injury and in atherosclerotic disease. Recent evidence indicates that during
      atherosclerosis, Toll-like receptors (TLRs) are activated in vascular cells by
      endogenous ligands. Here, we analyzed whether CLU expression in VSMC is
      controlled by TLRs, and stimulated by factors associated with or released by
      necrotic cells. Activation of TLR3 by the synthetic RNA analogue polyinosinic
      polycytidylic acid (poly(I:C)) in CRL2018 VSMC and in mice led to induction of
      CLU mRNA and protein synthesis, respectively. In TLR3-deficient 10A yolk sac
      cells, induction of CLU by poly(I:C) challenge depended on the ectopic expression
      of human TLR3. In mice lacking the TLR3-signaling adaptor protein TRIF (TIR
      domain-containing adaptor protein inducing IFN-beta) CLU induction by poly(I:C)
      was abrogated. In addition to poly(I:C) CLU gene expression in CRL2018 cells was
      induced by purified cellular RNA and RNA present in necrotic cell lysate. Our
      data indicate that cellular RNA following its release from necrotic cells in
      atherosclerotic lesions can act as an endogenous TLR3 ligand to induce CLU
      expression in VSMC and in vivo. Thus, they expand the view on TLR2 and TLR4 as
      known pro-atherosclerotic effectors toward TLR3. Conclusively, TLR3 activation
      induces expression of cytoprotective and anti-inflammatory CLU by VSMC and mice,
      to potentially counteract atherosclerotic pathology.

PMID- 20692255
TI  - Evaluation of functional integrity of the retinohypothalamic tract in advanced
      glaucoma using multifocal electroretinography and light-induced melatonin
      suppression.
AB  - The aim of the study was to investigate the survival of melanopsin-expressing
      retinal ganglion cells (mRGCs) and the functional integrity of the
      retinohypothalamic tract in patients with bilateral advanced glaucomatous optic
      neuropathy by measuring the neuroendocrine light response of the pineal gland.
      Nine patients with bilateral advanced primary open-angle glaucoma (glaucoma
      group) and nine normal control subjects (control group) were included in this
      pilot observational, prospective, case-control study. The best-corrected visual
      acuity logMAR, standard automated perimetry mean deviation, and the retinal nerve
      fiber layer thickness determined by optical coherence tomography and multifocal
      electroretinography were used to evaluate the changes. Melatonin was analyzed in
      the saliva by radioimmunoassay before and after exposure to bright light (600
      lux) for 60 min at night. The advanced glaucoma group did not have any
      significant nocturnal melatonin suppression after exposure to bright light (14.28
      +/- 3.07 pg/ml pre-light melatonin concentration vs. 15.22 +/- 3.56 pg/ml after
      light exposure; p = 0.798) unlike the marked melatonin suppression in the control
      group (22.43 +/- 4.37 pg/ml pre-light melatonin concentration vs. 11.25 +/- 1.89
      pg/ml after light exposure; p < 0.002). Response density estimates by the scalar
      product amplitude measure for the interval 0-80 ms of the first-order kernel
      responses were similar in both groups, indicating that outer retinal function was
      significantly unchanged in the glaucoma group (5.95 +/- 0.54 nV/dg^2) compared
      with the control group (6.20 +/- 0.22 nV/dg^2) (p = 0.689). Our findings are
      consistent with the interpretation that the rhythmic secretion of melatonin was
      affected in advanced glaucoma, suggesting that attention should be paid to non
      image-forming visual functions, such as control of circadian rhythm and the
      clinical impact in patients with glaucoma.

PMID- 20692256
TI  - Subtypes of Cryptosporidium spp. in mice and other small mammals.
AB  - DNA sequence analysis of the 60 kDa glycoprotein (gp60) gene has been used
      extensively in subtyping Cryptosporidium hominis in humans and Cryptosporidium
      parvum in humans and ruminants. In this study, nucleotide sequences of the gp60
      gene were obtained from seven Cryptosporidium species and genotypes related to
      the two species. Altogether, seven subtype families were detected, including four
      new subtype families. These data should be useful in studies of the transmission
      and zoonotic potential of cryptosporidiosis in mice and small wild mammals.

PMID- 20692257
TI  - Leishmania amazonensis: partial purification and study of the biochemical
      properties of the telomerase reverse transcriptase activity from promastigote
      stage.
AB  - Telomeres are protein-DNA complexes that protect chromosome ends from degradation
      and fusion. In Leishmania spp., telomeric DNA comprises a conserved TTAGGG repeat
      and is maintained by telomerase. Telomerase is a multisubunit enzymatic complex
      that ensures the complete DNA replication by adding new telomeric repeats to the
      G-rich strand. In this report we aimed to purify and study the biochemical
      properties of Leishmania amazonensis telomerase. In a first trial we used
      affinity chromatography with antisense 2'-O-methyl oligonucleotide without
      success since the Leishmania telomerase, similarly to Trypanosoma cruzi enzyme,
      was not eluted by competition, but instead, it remained bound to the column.
      Partially purified L. amazonensis telomerase activity was achieved by
      fractionation of extracts on complementary ion exchange and Heparin columns.
      Further purification of these fractions on a G-rich telomeric DNA affinity
      chromatography enriched for telomerase activity. The knowledge of telomerase
      characteristics in Leishmania could help to develop new strategies to overcome
      leishmaniasis.

PMID- 20692258
TI  - Nuclear EGFR shuttling induced by ionizing radiation is regulated by
      phosphorylation at residue Thr654.
AB  - Nuclear localisation of EGFR is associated with treatment resistance of tumor
      cells. The aim of this study was to identify molecular targets to block nuclear
      shuttling of EGFR. Mutation of Thr654, located within the putative EGFR NLS
      demonstrated that phosphorylation of this residue is essential for nuclear EGFR
      shuttling following irradiation. Deletion of Thr654 blocked nuclear transport of
      EGFR, whereas mutation to Glu increased shuttling. Treatment with a peptide,
      corresponding to the phosphorylated NLS, abolished nuclear EGFR transport and
      reduced radiation-induced activation of DNA-PK, essential for DNA-repair. In
      accordance with that, lack of nuclear EGFR increased residual DNA damage in tumor
      cells and reduced cellular survival following irradiation. Blockage of nuclear
      EGFR shuttling may be a new strategy to fight treatment resistance.

PMID- 20692259
TI  - Appetite regulation: the central role of melatonin in Danio rerio.
AB  - Melatonin is the hormonal mediator of photoperiodic information to the central
      nervous system in vertebrates and allows the regulation of energy homeostasis
      through the establishment of a proper balance between energy intake and energy
      expenditure. The aim of this study was to evaluate the role of melatonin in
      appetite central control analyzing the involvement of this hormone in the
      regulation of feeding behavior in the zebrafish Danio rerio. For this purpose,
      the effect of two different melatonin doses (100nM and 1MUM) administered for 10
      days, via water, to zebrafish adults was evaluated at both physiological and
      molecular level and the effect of melatonin was considered in relation to the
      most prominent systems involved in appetite regulation. For the first time, in
      fact, melatonin control of food intake by the modulation of leptin, MC4R,
      ghrelin, NPY and CB1 gene expression was evaluated. The results obtained indicate
      that melatonin significantly reduces food intake and the reduction is in
      agreement with the changes observed at molecular level. A significant increase in
      genes codifying for molecules involved in feeding inhibition, such as leptin and
      MC4R, and a significant reduction in the major orexigenic signals including
      ghrelin, NPY and CB1 are showed here. Taken together these results support the
      idea that melatonin falls fully into the complex network of signals that regulate
      food intake thus playing a key role in central appetite regulation.

PMID- 20692260
TI  - Evidence for cell proliferation in the sheep brain and its down-regulation by
      parturition and interactions with the young.
AB  - Production of new neurons continues throughout life in the subventricular zone
      (SVZ) and the dentate gyrus (DG) of the hippocampus and is influenced by both
      endocrine and social factors. In sheep parturition is associated with the
      establishment of a selective bond with the young based on an olfactory learning.
      The possibility exists that endocrine changes at parturition together with
      interactions with the young modulate cell proliferation in the neurogenic zones.
      In the present study, we first investigated the existence of cell proliferation
      in sheep. Newly born cells labeled by the cell proliferation marker 5-bromo-2'
      deoxyuridine (BrdU) were found in the SVZ, the main olfactory bulb (MOB) and the
      DG and completely co-localized with Ki-67, another mitotic marker. Forty to 50%
      of the BrdU-labeled cells contained GFAP suggestive of the presence of neural
      stem cells. Secondly, parturition with or without interactions with the lamb for
      2 days, down-regulated the number of BrdU-labeled cells in the 3 proliferation
      sites in comparison to no pregnancy. An additional control provided evidence that
      this effect is specific to early postpartum period: estrus with interactions with
      males did not affect cell proliferation. Our results provide the first
      characterization of neural cell proliferation in the SVZ, the DG and unexpectedly
      in the MOB of adult sheep. We hypothesize that the down-regulation of cell
      proliferation observed in the early postpartum period could facilitate the
      olfactory perceptual and memory demands associated with maternal behavior by
      favouring the survival and integration of neurons born earlier.

PMID- 20692261
TI  - Expression of antibody variable region-human alkaline phosphatase fusion proteins
      in mammalian cells.
AB  - Antibody fragments and their fusion proteins are indispensable tools as
      immunoassay reagents in diagnostics and molecular/cellular biotechnology.
      However, bacterial expression of cloned antibody genes with correct tertiary
      structure is not always guaranteed because of the lack of proper folding
      machinery and/or post-translational modifications. In addition, frequently used
      bacterial alkaline phosphatase as a fusion partner generally shows lower specific
      activity than the mammalian enzyme, which hampers its wider use as a detection
      reagent. Here we tried to express the fusion proteins of antibody variable
      region(s) and secreted human placental alkaline phosphatase (SEAP) using
      mammalian cell culture. As a result, functional V(H)-SEAP and single-chain Fv
      SEAP fusion proteins were successfully obtained from COS-1 cells, which was
      confirmed by ELISA and Western blotting. This system will be applicable to the
      rapid production of various antibody-enzyme fusions suitable for ELISA and open
      sandwich ELISA that utilizes antigen-dependent V(H)/V(L) interaction for antigen
      quantitation.

PMID- 20692262
TI  - A cell-based luciferase-dependent assay for the quantitative determination of
      free extracellular adenosine with paracrine signaling activity.
AB  - Extracellular adenosine exerts powerful paracrine effects on immune cells. Thus,
      adenosine signaling has to be strictly regulated. This is achieved by its rapid
      internalization or enzymatic degradation. Consequently, free adenosine is
      extremely difficult to measure in cell culture systems and may escape from
      detection by time-consuming endpoint measurements like high-performance liquid
      chromatography (HPLC). Therefore, we have now developed a highly sensitive assay
      which enables the quantification of biologically relevant extracellular adenosine
      via the activation of an ectopically expressed Adenosine 2a-receptor (ADORA2A) in
      HEK-293 reporter cells. Binding of the short-lived nucleoside to this receptor
      induces a cAMP-dependent signal which can be detected via a cAMP-responsive
      luciferase construct. Tests with exogenously added adenosine confirmed that the
      resulting luminescence signals correlate with the respective adenosine levels and
      thus allow quantitative measurements in a range from 20 nM to 80 MUM free
      extracellular adenosine. Inhibition of adenosine uptake by dipyridamole further
      increased the sensitivity of the assay. We further validated our approach by
      quantifying the adenosine levels that are generated by regulatory T cells via
      ectonucleotidase-mediated cleavage of ATP. As expected, values returned to
      baseline when ADORA2A was inhibited. This confirmed that this new cell-based
      reporter assay constitutes a biologically relevant, technically easy, versatile,
      scalable and cost-effective approach that allows the non-radioactive
      quantification of adenosine as a signaling intermediate.

PMID- 20692263
TI  - Gene expression patterns of abalone, Haliotis tuberculata, during successive
      infections by the pathogen Vibrio harveyi.
AB  - Since 1998, episodic mass mortality of the abalone Haliotistuberculata has been
      observed along the northern Brittany coast of France caused by a complex
      interaction among the host, pathogen and environmental factors. In the present
      study, abalone were submitted to two successive infections with the pathogen
      Vibrioharveyi under controlled conditions. During the first challenge, infection
      by V.harveyi resulted in 64% mortality of mature abalone. After a second
      infection of those surviving the first challenge, only 44% mortality was
      observed. Physiological variability in the host response appears to be a major
      determinant in susceptibility to V.harveyi. In order to isolate differentially
      expressed genes in H.tuberculata challenged with this bacterium, suppression
      subtractive hybridization (SSH) cDNA libraries were constructed from muscle of
      moribund abalone (susceptibles), surviving individuals (apparently resistant to
      the bacterium) and control (unexposed) animals. Of the 1152 clones sequenced, 218
      different partial cDNA sequences were obtained and represented 69 known genes. Of
      these, 65 were identified for the first time in H.tuberculata. Using real-time
      PCR, a time-course study was conducted on 19 of the genes identified by SSH. A
      majority of differentially expressed transcripts were down-regulated in
      susceptible individuals as compared to their resistant counterparts. Bacterial
      challenge of abalone resulted in the up-regulation of three transcripts (encoding
      ferritin, heat shock protein HSP84 and fatty acid binding protein FABP) in those
      that survived exposure to V.harveyi. This study has identified potential
      candidates for further investigation into the functional basis of resistance and
      susceptibility to summer vibriosis outbreaks in abalone.

PMID- 20692264
TI  - Natriuretic peptide pharmacogenetics: membrane metallo-endopeptidase (MME):
      common gene sequence variation, functional characterization and degradation.
AB  - Membrane metallo-endopeptidase (MME), also known as neutral endopeptidase 24.11
      (EC 3.4.24.11), is involved in the metabolism of natriuretic peptides that play a
      key role in modulating cardiac structure and function. Common genetic variation
      in MME has not been addressed by resequencing the gene using DNA from different
      ethnic populations. We set out to identify and functionally characterize common
      genetic variation in MME in three ethnic groups. DNA samples from 96 European
      American, 96 African-American, and 96 Han Chinese-American healthy subjects were
      used to resequence MME. Ninety polymorphisms, 65 novel, were identified,
      including 8 nonsynonymous single nucleotide polymorphisms (nsSNPs). Expression
      constructs for the nsSNPs were created and COS-1 cells were transfected with
      constructs for wild type (WT) and variant allozymes. Recombinant proteins were
      analyzed by quantitative Western blot analysis and by a one-step fluorometric
      assay. A significant reduction in enzyme activity (21% of WT) and immunoreactive
      protein (29% of WT) for the Val73 variant allozyme was observed. Proteasome
      mediated degradation and autophagy participated in the degradation of this
      variant allozyme. The chaperone proteins, BiP and GRP94, were upregulated after
      transfection with Val73 MME, suggesting protein misfolding, compatible with
      conclusions based on the MME X-ray crystal structure. Multiple novel
      polymorphisms of MME were identified in three ethnic groups. The Val73 variant
      allozyme displayed a significant decrease in MME protein quantity and activity,
      with degradation mediated by both proteasome and autophagy pathways. This
      polymorphism could have a significant effect on the metabolism of natriuretic
      peptides.

PMID- 20692265
TI  - Roles of phospho-GSK-3beta in myocardial protection afforded by activation of the
      mitochondrial K ATP channel.
AB  - The aim of this study was to determine the roles of glycogen synthase kinase
      3beta (GSK-3beta) in cardioprotection by activation of the mitochondrial ATP
      sensitive K(+) channel (mK(ATP) channel). In isolated rat hearts, an mK(ATP)
      activator, diazoxide, and a GSK-3beta inhibitor, SB216763, similarly limited
      infarct size and the combination of these agents did not afford further
      protection. The protection by pre-ischemic treatment with diazoxide was abolished
      by inhibition of protein kinase C-epsilon (PKC-epsilon) or phosphatidylinositol-3
      kinase (PI3K) upon reperfusion. Infusion of a GSK-3beta inhibitor (LiCl), but not
      diazoxide, during reperfusion limited infarct size. Inhibition of PKC-epsilon or
      PI3K did not affect the protection by LiCl. Diazoxide infusion alone did not
      induce GSK-3beta phosphorylation. However, diazoxide infusion before ischemia
      increased mitochondrial phospho-GSK-3beta level and reduced cyclophilin-D (CypD)
      binding to adenine nucleotide translocase (ANT) at 10 min after reperfusion. This
      diazoxide-induced GSK-3beta phosphorylation was inhibited by blockade of the
      mK(ATP) channel before ischemia and by blockade of PKC-epsilon, PI3K or the
      adenosine A2b receptor at the time of reperfusion. Inhibition of GSK-3beta by
      LiCl during reperfusion increased phospho-GSK-3beta but had no significant effect
      on CypD-ANT binding. These results suggest that GSK-3beta phosphorylation at the
      time of reperfusion by a PKC-epsilon, PI3K- and A2b receptor-dependent mechanism
      contributes to prevention of myocardial necrosis by pre-ischemic activation of
      the mK(ATP) channel. Inhibition of CypD-ANT interaction may contribute to mK(ATP)
      induced myocardial protection, though it is not the sole mechanism of phospho-GSK
      3beta-mediated cytoprotection.

PMID- 20692266
TI  - An association between gene expression and better survival in female mice
      following myocardial infarction.
AB  - Following myocardial infarction, the prognosis for females is better than males.
      Estrogen is thought to be protective, but clinical trials with hormone
      replacement failed to show protection. Here, we sought to identify novel
      mechanisms that might explain this sex-based difference. By diverging from the
      traditional focus on sex hormones, we employed a conceptually novel approach to
      this question by using a non-biased approach to measure global changes in gene
      expression following infarction. We hypothesized that specific gene programs are
      initiated in the heart following infarction that might account for this sex-based
      difference. We induced small, medium, and large infarcts in male and female mice
      and measured changes in gene expression by microarray following infarction.
      Regardless of infarct size, survival was better in females, while mortality
      occurred 3-10 days following infarction in males. Two days following infarction,
      males developed significant ventricular dilation, the best predictor of mortality
      in humans. Three days following infarction, we measured gene expression by
      microarray, comparing male versus female and sham versus surgery/infarction. In
      general, our results indicate a higher relative level of gene induction in
      females versus males and identified programs for angiogenesis, extracellular
      matrix remodeling, and immune response. This pattern of gene expression was
      linked to less pathologic remodeling in female hearts, including increased
      capillary density and decreased fibrosis. In summary, our results suggest an
      association between improved survival and less pathologic remodeling and the
      relative induction of gene expression in females following myocardial infarction.

PMID- 20692267
TI  - Angiotensin II inhibits the electrogenic Na+/HCO3- cotransport of cat cardiac
      myocytes.
AB  - The Na(+)/HCO(3)(-) cotransporter (NBC) plays an important role in intracellular
      pH (pH(i)) regulation in the heart. In the myocardium co-exist the electrogenic
      (eNBC) and electroneutral (nNBC) isoforms of NBC. We have recently reported that
      angiotensin II (Ang II) stimulated total NBC activity during the recovery from
      intracellular acidosis through a reactive oxygen species (ROS) and ERK-dependent
      pathway. In the present work we focus our attention on eNBC. In order to study
      the activity of the eNBC in isolation, we induced a membrane potential
      depolarization by increasing extracellular K(+) [K(+)](o) from 4.5 to 45 mM (K(+)
      pulse). This experimental protocol enhanced eNBC driving force leading to
      intracellular alkalization (0.19 +/- 0.008, n=6; data expressed as an increase of
      pH(i) units after 14 min of applying the K(+) pulse). This alkalization was
      completely abrogated by the NBC blocker S0859 (-0.004 +/- 0.016*, n=5; *
      indicates p<0.05 vs control) but not by the Na(+)/H(+) exchanger blocker HOE642
      (0.185 +/- 0.04, n=4), indicating that we are exclusively measuring eNBC. The
      K(+) pulse induced alkalization was canceled by 100 nM Ang II (-0.008 +/- 0.018*;
      n=5). This inhibitory effect was prevented when the myocytes were incubated with
      losartan (AT(1) receptor blocker, 0.18 +/- 0.02; n=4) or SB202190 (p38 MAP kinase
      inhibitor, 0.25 +/- 0.06; n=5). Neither chelerythrine (PKC inhibitor, -0.06 +/-
      0.04*; n=4), nor U0126 (ERK inhibitor, -0.07 +/- 0.04*; n=4) nor MPG (ROS
      scavenger, -0.02 +/- 0.05*; n=8) affected the Ang II-induced inhibition of eNBC.
      The inhibitory action of Ang II on eNBC was corroborated with perforated patch
      clamp experiments, since no impact of the current produced by eNBC on action
      potential repolarization was observed in the presence of Ang II. In conclusion,
      we propose that Ang II, binding to AT(1) receptors, exerts an inhibitory effect
      on eNBC activity in a p38 kinase-dependent manner.

PMID- 20692268
TI  - Allogeneic administration of fetal membrane-derived mesenchymal stem cells
      attenuates acute myocarditis in rats.
AB  - We reported previously that the autologous administration of bone marrow-derived
      mesenchymal stem cells (BM-MSC) significantly attenuated myocardial dysfunction
      and injury in a rat model of acute myocarditis by stimulating angiogenesis and
      reducing inflammation. Because BM aspiration procedures are invasive and can
      yield low numbers of MSC after processing, we focused on fetal membranes (FMs) as
      an alternative source of MSC to provide a large number of cells. We investigated
      whether the allogeneic administration of FM-derived MSC (FM-MSC) attenuates
      myocardial injury and dysfunction in a rat myocarditis model. Experimental
      autoimmune myocarditis (EAM) was induced in male Lewis rats by injecting porcine
      cardiac myosin. Allogeneic FM-MSC obtained from major histocompatibility complex
      mismatched ACI rats (5 * 10(5) cells/animal) were injected intravenously into
      Lewis rats one week after myosin administration. At day 21, severe cardiac
      inflammation and deterioration of cardiac function were observed. The allogeneic
      administration of FM-MSC significantly attenuated inflammatory cell infiltration
      and monocyte chemoattractant protein 1 expression in the myocardium and improved
      cardiac function. In a T-lymphocyte proliferation assay, the proliferative
      response of splenic T lymphocytes was significantly lower in cells obtained from
      FM-MSC-treated EAM rats that reacted to myosin than in cells obtained from
      vehicle-treated rats with EAM. T-lymphocyte activation was significantly reduced
      by coculture with FM-MSC. The allogeneic administration of FM-MSC attenuated
      myocardial dysfunction and inflammation, and the host cell-mediated immune
      response was attenuated in a rat model of acute myocarditis. These results
      suggest that allogeneic administration of FM-MSC might provide a new therapeutic
      strategy for the treatment of acute myocarditis.

PMID- 20692269
TI  - Human RegIV protein adopts a typical C-type lectin fold but binds mannan with two
      calcium-independent sites.
AB  - Human RegIV protein, which contains a sequence motif homologous to calcium
      dependent (C-type) lectin-like domain, is highly expressed in mucosa cells of the
      gastrointestinal tract during pathogen infection and carcinogenesis and may be
      applied in both diagnosis and treatment of gastric and colon cancers. Here, we
      provide evidence that, unlike other C-type lectins, human RegIV binds to
      polysaccharides, mannan, and heparin in the absence of calcium. To elucidate the
      structural basis for carbohydrate recognition by NMR, we generated the mutant
      with Pro91 replaced by Ser (hRegIV-P91S) and showed that the structural property
      and carbohydrate binding ability of hRegIV-P91S are almost identical with those
      of wild-type protein. The solution structure of hRegIV-P91S was determined,
      showing that it adopts a typical fold of C-type lectin. Based on the chemical
      shift perturbations of amide resonances, two calcium-independent mannan-binding
      sites were proposed. One site is similar to the calcium-independent sugar-binding
      site on human RegIII and Langerin. Interestingly, the other site is adjacent to
      the conserved calcium-dependent site at position Ca-2 of typical C-type lectins.
      Moreover, model-free analysis of (15)N relaxation parameters and simplified Carr
      Purcell-Meiboom-Gill relaxation dispersion experiments showed that a slow
      microsecond-to-millisecond time-scale backbone motion is involved in mannan
      binding by this site, suggesting a potential role for specific carbohydrate
      recognition. Our findings shed light on the sugar-binding mode of Reg family
      proteins, and we postulate that Reg family proteins evolved to bind sugar without
      calcium to keep the carbohydrate recognition activity under low-pH environments
      in the gastrointestinal tract.

PMID- 20692270
TI  - Herbivore-induced coexistence of competing plant species.
AB  - We study a series of spatially implicit lottery models in which two competing
      plant species, with and without defensive traits, are grazed by a herbivore in a
      homogeneous habitat. One species (palatable) has no defensive traits, while the
      other (defended) has defensive traits but suffers reduced reproduction as the
      result of an assumed trade-off. Not surprisingly, coexistence of these plants
      cannot occur when the herbivore density is very low (the palatable plant always
      wins) or very high (the defended plant wins). At intermediate densities, however,
      herbivory can mediate plant coexistence, even in a homogeneous environment. If
      the herbivore eats several plants per bite, and its forage-selection depends on
      the average palatability of the plants it eats, then palatable species in the
      immediate neighbourhood of defended plants may be more likely to persist
      (associational resistance) even at higher grazing pressure. If the herbivore
      shows a positive numerical response to the average palatability of the habitat as
      a whole, then both plant populations are stabilized and coexistence is promoted,
      because both species obtain a minority advantage through the negative feedback
      caused by herbivory. If the herbivore exhibits both of these traits, the system
      may have at most two non-trivial equilibria, one of which is stable and the other
      unstable. This means that coexistence in such a system is vulnerable to large
      fluctuations in herbivore density and identity, and this has implications for
      conservation in systems where large herbivores are managed to promote plant
      diversity.

PMID- 20692271
TI  - Inappropriate statistical analyses lead to erroneous results [Focke et al.,
      Mutation Research 683 (2010) 74-83].

PMID- 20692273
TI  - Modulation of DNA repair capacity and mRNA expression levels of XRCC1, hOGG1 and
      XPC genes in styrene-exposed workers.
AB  - Decreased levels of single-strand breaks in DNA (SSBs), reflecting DNA damage,
      have previously been observed with increased styrene exposure in contrast to a
      dose-dependent increase in the base-excision repair capacity. To clarify further
      the above aspects, we have investigated the associations between SSBs,
      micronuclei, DNA repair capacity and mRNA expression in XRCC1, hOGG1 and XPC
      genes on 71 styrene-exposed and 51 control individuals. Styrene concentrations at
      workplace and in blood characterized occupational exposure. The workers were
      divided into low (below 50 mg/m3) and high (above 50 mg/m3)) styrene exposure
      groups. DNA damage and DNA repair capacity were analyzed in peripheral blood
      lymphocytes by Comet assay. The mRNA expression levels were determined by qPCR. A
      significant negative correlation was observed between SSBs and styrene
      concentration at workplace (R=-0.38, p=0.001); SSBs were also significantly
      higher in men (p=0.001). The capacity to repair irradiation-induced DNA damage
      was the highest in the low exposure group (1.34+/-1.00 SSB/109 Da), followed by
      high exposure group (0.72+/-0.81 SSB/109 Da) and controls (0.65+/-0.82 SSB/109
      Da). The mRNA expression levels of XRCC1, hOGG1 and XPC negatively correlated
      with styrene concentrations in blood and at workplace (p<0.001) and positively
      with SSBs (p<0.001). Micronuclei were not affected by styrene exposure, but were
      higher in older persons and in women (p<0.001). In this study, we did not confirm
      previous findings on an increased DNA repair response to styrene-induced
      genotoxicity. However, negative correlations of SSBs and mRNA expression levels
      of XRCC1, hOGG1 and XPC with styrene exposure warrant further highly-targeted
      study.

PMID- 20692274
TI  - Ciguatera fish poisoning on the West Africa Coast: An emerging risk in the Canary
      Islands (Spain).
AB  - Ciguatera fish poisoning (CFP) is endemic in certain tropical and subtropical
      regions of the world. CFP had not been described on the West Africa Coast until a
      2004 outbreak in the Canary Islands. In 2008-2009, two additional outbreaks of
      ciguatera occurred. Individuals afflicted had consumed lesser amberjack (Seriola
      rivoliana) captured from nearby waters. Caribbean ciguatoxin-1 (C-CTX-1) was
      confirmed in fish samples by LC-MS/MS. Ciguatoxic fish in this region may pose a
      new health risk for the seafood consumer.

PMID- 20692275
TI  - Reassessment of the toxin profile of Cylindrospermopsis raciborskii T3 and
      function of putative sulfotransferases in synthesis of sulfated and sulfonated
      PSP toxins.
AB  - The toxigenic freshwater cyanobacterium Cylindrospermopsis raciborskii T3 has
      been used as a model to study and elucidate the biosynthetic pathway of
      tetrahydropurine neurotoxins associated with paralytic shellfish poisoning (PSP).
      There are nevertheless several inconsistencies and contradictions in the toxin
      profile of this strain as published by different research groups, and claimed to
      include carbamoyl (STX, NEO, GTX2/3), decarbamoyl (dcSTX), and N-sulfocarbamoyl
      (C1/2, B1) derivatives. Our analysis of the complete genome of another PSP toxin
      producing cyanobacterium, Raphidiopsis brookii D9, which is closely related to C.
      raciborskii T3, resolved many issues regarding the correlation between
      biosynthetic pathways, corresponding genes and the T3 toxin profile. The putative
      sxt gene cluster in R. brookii D9 has a high synteny with the T3 sxt cluster,
      with 100% nucleotide identity among the shared genes. We also compared the PSP
      toxin profile of the strains by liquid chromatography coupled to mass
      spectrometry (LC-MS/MS). In contrast to published reports, our reassessment of
      the PSP toxin profile of T3 confirmed production of only STX, NEO and dcNEO. We
      gained significant insights via correlation between specific sxt genes and their
      role in PSP toxin synthesis in both D9 and T3 strains. In particular, analysis of
      sulfotransferase functions for SxtN (N-sulfotransferase) and SxtSUL (O
      sulfotransferase) enzymes allowed us to propose an extension of the PSP toxin
      biosynthetic pathway from STX to the production of the derivatives GTX2/3, C1/2
      and B1. This is a significantly revised view of the genetic mechanisms underlying
      synthesis of sulfated and sulfonated STX analogues in toxigenic cyanobacteria.

PMID- 20692276
TI  - Age related acute effects of microcystin-LR on Daphnia magna biotransformation
      and oxidative stress.
AB  - As a result of eutrophication among other factors, bloom forming species of
      cyanobacteria frequently thrive and dominate communities in freshwater
      ecosystems. Cyanobacteria are considered as a nuisance and hazardous due to the
      production of toxins. The most potent and studied cyanobacterial toxins are the
      microcystins, especially the variant microcystin-LR (MC-LR). Daphnia magna plays
      a central role in freshwater pelagic food webs and its populations are negatively
      affected by cyanobacteria due to nutritional inadequacy, feeding interference and
      toxic effects on growth and reproduction. Biotransformation and antioxidant
      enzymes, amongst others enable D. magna capacity to cope with MC-LR up to a
      certain concentration. Aim of our study was to investigate the age related acute
      effects of MC-LR on D. magna biotransformation and antioxidant enzymes
      (glutathione S-transferase, GST and catalase, CAT), subsequent lipid peroxidation
      and furthermore to lactate and the enzyme lactate dehydrogenase (LDH). D. magna
      neonates (<3 days old) and young adults (7 days old), were exposed to increasing
      concentrations of MC-LR (up to 100 MUg/L) for 24 and 48 h. D. magna sGST
      activities at both ages, but more pronounced in adults, increased at low MC-LR
      concentrations followed by decreased activities at the higher ones suggesting
      diminished ability to biotransform the cyanotoxin. Oxidative protection was more
      efficient in neonates, where CAT was elevated strongly and contributed to buffer
      oxidative stress, evidenced by the constant TBARS concentrations. LDH was
      negatively affected by MC-LR exposure leading to constant and low concentrations
      of lactate. As this enzyme is involved in the production of rapidly required
      energy, the findings suggest an energetic impairment due to MC-LR.

PMID- 20692277
TI  - Actinoporins from the sea anemones, tropical Radianthus macrodactylus and
      northern Oulactis orientalis: Comparative analysis of structure-function
      relationships.
AB  - Actinoporins Or-A and Or-G from the northern sea anemone Oulactis orientalis and
      actinoporins RTX-A and RTX-SII from the tropical sea anemone Radianthus
      macrodactylus (=Heteractis crispa) were compared with each other and with some
      known actinoporins. In this work the complete amino acid sequence of RTX-SII was
      determined by molecular biology methods. The following differences were revealed
      in functionally significant regions of Radianthus, Oulactis, and some other
      actinoporins: (i) tryptophan is substituted for leucine in the position
      equivalent to Trp112 in the POC binding site of EqtII; (ii) 13 and 5 residues are
      truncated in N-terminal regions of Or-A and Or-G, respectively. A possible role
      of these structural differences in specific regions of the actinoporin sequence
      was analyzed. Some differences in hydrophobicity parameters, distribution of
      charged residues, and length of actinoporins' N-terminus apparently cause
      considerable differences in their hemolytic activities. Homology models of
      Radianthus and Oulactis actinoporin monomers were generated using crystal
      structures of equinatoxin II from Actinia equina and sticholysin II from
      Stichodactyla helianthus as templates. The current data on actinoporin structures
      and activities, coupled with results of our earlier differential scanning
      calorimetric and electrophoretic experiments with RTX-A-modified erythrocyte
      ghosts (Shnyrov et al., 1992), suggests that the exposed RGD motif located near
      the POC binding site can interact with membrane integrin(s).

PMID- 20692279
TI  - Grasping remembered objects: exponential decay of the visual memory.
AB  - The accuracy with which goal-directed movements are executed depends
      substantially on the availability of accurate visuomotor information. When no
      visual information is available during movement execution, movement kinematics
      change and become more variable, indicating that the visual information about the
      movement environment is stored for a restricted period of time. However, little
      is known about the underlying decay characteristics. In this study we
      investigated how increasing memory demands change the kinematics of a grasping
      movement and whether these alterations reflect a continuous or an abrupt decay of
      the underlying visuomotor memory. Ten participants grasped differently sized
      objects under a full vision condition and four different delay conditions.
      Results show that the visuomotor information used for grasping decays rapidly
      after visual occlusion. The information decay over time became obvious in a
      decrease of movement accuracy and an increase in movement variability that were
      both well described by exponential decay models. Our findings suggest that
      visuomotor information is represented in some sort of short-term memory showing
      the same decay characteristics as observed in classical memory research.

PMID- 20692280
TI  - Dendrite plasticity in the lateral geniculate nucleus in primate glaucoma.
AB  - Neural degeneration in glaucoma involves retinal ganglion cells and neurons of
      their major target, the lateral geniculate nucleus (LGN). Dendrites of relay LGN
      neurons projecting to the visual cortex were studied by immunocytochemical and
      quantitative Sholl analysis in combination with confocal microscopy and 3D
      morphometry. In non-human adult primate glaucoma, relay LGN neurons showed
      reduced dendrite complexity and length, and these changes were modified by NMDA
      receptor blockade. Dendrite plasticity of LGN relay neurons in adult primate
      glaucoma has implications for potential disease modification by treatment
      interventions.

PMID- 20692281
TI  - Coronary heart disease risk underestimation in a minority population: the Bronx
      Coronary Risk Perception Study.

PMID- 20692282
TI  - Sustained body weight reduction by an individual-based lifestyle intervention for
      workers in the construction industry at risk for cardiovascular disease: results
      of a randomized controlled trial.
AB  - OBJECTIVE: To evaluate the effectiveness of a lifestyle intervention for male
      workers in the construction industry at risk of cardiovascular disease (CVD).
      METHODS: In a randomized controlled trial performed in the Netherlands between
      2007 and 2009, usual care was compared to 6 months of individual counseling using
      motivational interviewing techniques, delivered face to face and by telephone.
      Participants aimed at improving energy balance-related behavior or smoking
      cessation. Linear regression analyses were performed to determine the effects.
      RESULTS: Body weight had significantly decreased at 6 (beta=-1.9, 95% CI -2.6; 
      1.2) and 12 months (beta=-1.8, 95%CI -2.8; -1.1). The intervention effects were
      also significant for diastolic blood pressure at 6 months (beta=-1.7, 95% CI 
      3.3; -0.1). Among participants who had aimed at energy balance, the intervention
      had a significant favorable effect on body weight at 6 (beta=-2.1, 95% CI -2.9; 
      1.3) and 12 months (beta=-2.2, 95% CI -3.1; -1.3) and at HDL cholesterol
      (beta=0.05, 95% CI 0.01; 0.10) and HbA1c (beta=-0.06, 95%CI -0.12; -0.001) at 12
      months, although there was no intervention effect on these variables over time.
      CONCLUSION: Individual-based counseling resulted in significant beneficial long
      term effects on body weight. This is an important finding for occupational
      health, considering the rising prevalence of obesity and CVD.

PMID- 20692278
TI  - Imaging retinotopic maps in the human brain.
AB  - A quarter-century ago visual neuroscientists had little information about the
      number and organization of retinotopic maps in human visual cortex. The advent of
      functional magnetic resonance imaging (MRI), a non-invasive, spatially-resolved
      technique for measuring brain activity, provided a wealth of data about human
      retinotopic maps. Just as there are differences amongst non-human primate maps,
      the human maps have their own unique properties. Many human maps can be measured
      reliably in individual subjects during experimental sessions lasting less than an
      hour. The efficiency of the measurements and the relatively large amplitude of
      functional MRI signals in visual cortex make it possible to develop quantitative
      models of functional responses within specific maps in individual subjects.
      During this last quarter-century, there has also been significant progress in
      measuring properties of the human brain at a range of length and time scales,
      including white matter pathways, macroscopic properties of gray and white matter,
      and cellular and molecular tissue properties. We hope the next 25years will see a
      great deal of work that aims to integrate these data by modeling the network of
      visual signals. We do not know what such theories will look like, but the
      characterization of human retinotopic maps from the last 25years is likely to be
      an important part of future ideas about visual computations.

PMID- 20692283
TI  - What are physicians' and patients' beliefs about diet, weight, exercise, and
      smoking cessation counseling?

PMID- 20692284
TI  - Hypertension awareness, treatment and control in an urban low-income setting: a
      community-based study in Singapore.

PMID- 20692285
TI  - Interaction of proteinase inhibitors with phospholipid vesicles is modulated by
      pH.
AB  - rBbKI and rBbCI, plant recombinant inhibitors from Bauhinia bauhinioides, and
      BpuTI from Bauhinia purpurea seeds distinctly and specifically block proteolytic
      enzymes. The secondary structures of those inhibitors were compared and their
      interactions with phospholipid vesicles were evaluated by the release of calcein
      and by intrinsic fluorescence of tryptophan residues. The results show that
      rBbKI, rBbCI and BpuTI are able to interact with phospholipd vesicles and induce
      membrane permeabilization in a concentration- and pH-dependent manner. The
      leakage was rapid and extensive at pH 4.5, but at physiological pH, no calcein
      release was observed. These results may suggest that upon inflammation or
      microorganism invasion accompanied by lowering of pH, appropriate conditions may
      occur for the inhibitors to interact with cell membrane and act on specific
      proteolytic enzyme.

PMID- 20692286
TI  - Scophthalmus maximus cystatin B enhances head kidney macrophage-mediated
      bacterial killing.
AB  - Cystatins form a large family of cysteine protease inhibitors found in a wide
      arrange of organisms. Studies have indicated that mammalian cystatins play
      important roles under both physiological and pathological conditions. However,
      much less is known about fish cystatins. In this report, we described the
      identification and analysis of a cystatin B homologue, SmCytB, from turbot
      Scophthalmus maximus. The open reading frame of SmCytB is 300bp, which encodes a
      99-residue protein that shares high levels of sequence identities with the
      cystatin B of a number of fish species and contains the conserved cysteine
      protease inhibitor motif of cystatin B. Constitutive expression of SmCytB is high
      in muscle, brain, heart and liver, and low in spleen, blood, gill and kidney.
      Bacterial infection upregulates SmCytB expression in kidney, spleen, liver and
      brain but not in muscle or heart. Functional analysis showed that recombinant
      SmCytB purified from Escherichia coli exhibits apparent cysteine protease
      inhibitor activity. Transient overexpression of SmCytB in head kidney macrophages
      enhances macrophage bactericidal activity probably through a nitric oxide
      independent mechanism. These results indicate that SmCytB is involved in the
      immune defense of turbot against bacterial infection.

PMID- 20692287
TI  - Molecular characterisation of Toll-like receptors in the black flying fox
      Pteropus alecto.
AB  - Bats are believed to be reservoir hosts for a number of emerging and re-emerging
      viruses, many of which are responsible for illness and mortality in humans,
      livestock and other animals. In other vertebrates, early responses to viral
      infection involve engagement of Toll-like receptors (TLRs), which induce changes
      in gene expression collectively leading to an "antiviral state". In this study we
      report the cloning and bioinformatic analysis of a complete set of TLRs from the
      black flying fox Pteropus alecto, and perform quantitative tissue expression
      analysis of the nucleic acid-sensing TLRs 3, 7, 8 and 9. Full-length mRNA
      transcripts from TLRs homologous to human TLRs 1-10 were sequenced, as well as a
      nearly intact TLR13 pseudogene that was spliced and polyadenylated. This
      prototype data can now be used to design functional studies of the bat innate
      immune system.

PMID- 20692288
TI  - 17beta-Estradiol regulates gilthead seabream professional phagocyte responses
      through macrophage activation.
AB  - In mammals, estrogens regulate the immune system, either directly or indirectly
      via several leukocyte types through autocrine/paracrine mechanisms. In the
      gilthead seabream (Sparus aurata L.) gonad, an intensive remodeling process
      accompanied by the massive infiltration of acidophilic granulocytes (AG) is
      partially triggered by 17beta-estradiol (E(2)). Once AG infiltrated the gonad,
      show impaired activities. In this study we first demonstrate that neither
      testicular nor head-kidney AG express any of the three estrogen receptor (ER)
      genes (ERa, ERb1 and ERb2) described in the gilthead seabream, while head-kidney
      macrophages (Mc) and lymphocytes (Ly) constitutively express ERa gene. Moreover,
      Mc are important in the immune-modulatory role of E(2), as suggested by its
      ability to induce ERb2 gene expression and up-regulate the expression of genes
      coding for ERa, ERb1, pro-inflammatory cytokines, chemokines and tissue
      remodeling molecules. Furthermore, the soluble factors produced by E(2)-treated
      Mc decreased in head-kidney phagocytes, their phagocytic ability and capacity,
      while no effects were observed on their reactive oxygen intermediate (ROI)
      production or their migratory capabilities. However, the role of Ly in the
      regulation of AG migration and the modulation of phagocytic and ROI production
      activities triggered by E(2) can not be ruled out, so that further studies are
      necessary to clarify these issues.

PMID- 20692289
TI  - Synthetic double-stranded RNA oligonucleotides are immunostimulatory for chicken
      spleen cells.
AB  - Toll-like receptors (TLRs) are an integral part of the innate immune system that
      recognize microbe-derived molecular patterns and initiate innate and adaptive
      defenses against invading pathogens. TLR3 and TLR7 are involved in sensing virus
      associated single-stranded and double-stranded RNA (dsRNA) molecules in cellular
      endosomes to activate the type I interferon pathway in mammals. Although certain
      synthetic dsRNA molecules have been identified to show immunostimulation in
      mammalian cells, very little is known about the ability of these sequences to
      stimulate avian cells. The current study investigated immunostimulatory
      properties of four synthetic oligonucleotide sequences using chicken splenocytes.
      Expression of TLR3 and 7, type I interferons and several other cytokines as well
      as TLR signaling pathway-related genes at different time points post-stimulation
      was quantified by real-time PCR. A dose-dependent increase in expression of TLR3
      was observed in splenocytes treated with poly-UGUGU (poly-UG) and beta
      galactosidase dsRNA molecules. TLR3 and TLR7 gene expression was significantly up
      regulated upon stimulation with all four dsRNA molecules. Furthermore, in a time
      course study, a significant increase was noted in the expression of TLR3, TLR7,
      interferon (IFN)-alpha, IFN-beta, interleukin (IL)-1beta, IL-6 as well as 2',5'
      OAS in splenocytes treated with poly-UG. In conclusion, the present study
      demonstrated the immunostimulatory properties of dsRNA oligonucleotides,
      especially those that contain a poly-UG motif, in chickens.

PMID- 20692290
TI  - Study of community-acquired pneumonia: incidence, patterns of care, and outcomes
      in primary and hospital care.
AB  - BACKGROUND: To asses the incidence, patterns of care, and outcomes of community
      acquired pneumonia (CAP) in the population of a defined geographic area. METHODS:
      Prospective study conducted from April 1, 2006, to June 30, 2007. All adult
      patients (age >=18) with CAP in the Comarca Interior region of northern Spain
      were identified through the region's 150 family physicians and the emergency
      department (ED) of the area's general teaching hospital. RESULTS: During a 15
      month period, 960 patients with CAP were identified: 418 hospitalized and 542
      ambulatory patients. The hospitalization rate was 43.5% and the global 30-day
      mortality was 4% (38 patients). Of the patients treated at home, most (90.4%) had
      mild pneumonia, only 3.1% (17 patients) were subsequently hospitalized, with a 30
      day mortality rate of 0%. However, 48.9% were not treated according to antibiotic
      recommendations of the Spanish Society of Pneumology. Mean duration of return to
      daily activity was 18.8 days for the entire population. The incidence study was
      restricted to the first 12 months, during which 787 patients fulfilled the
      inclusion criteria. This represented an incidence of pneumonia of 3.1/1000 adults
      per year. Both the incidence of CAP and hospitalization for it rose with age.
      CONCLUSIONS: Our study offers information about CAP in the general population and
      provides feedback for the management of CAP. Although the selection of patients
      to be treated at home was appropriate, the choice of empiric antibiotic therapy
      for ambulatory CAP was problematic.

PMID- 20692291
TI  - A three-dimensional digital segmented and deformable brain atlas of the domestic
      pig.
AB  - We used high-magnetic field (4.7 T) magnetic resonance imaging (MRI) to build the
      first high-resolution (100 microm x 150 microm x 100 microm) three-dimensional
      (3D) digital atlas in stereotaxic coordinates of the brain of a female domestic
      pig (Sus scrofa domesticus). This atlas was constructed from one hemisphere which
      underwent a symmetrical transformation through the midsagittal plane. Concomitant
      construction of a 3D histological atlas based on the same scheme facilitated
      control of deep brain structure delimitation and enabled cortical mapping to be
      achieved. The atlas contains 178 individual cerebral structures including 42
      paired and 9 single deep brain structures, 5 ventricular system areas, 6 paired
      deep cerebellar nuclei, 12 cerebellar lobules and 28 cortical areas per
      hemisphere. Given the increasing importance of pig brains in medical research,
      this atlas should be a useful tool for intersubject normalization in anatomical
      imaging as well as for precisely localizing brain areas in functional MR studies
      or electrode implantation trials. The atlas can be freely downloaded from our
      institution's Website.

PMID- 20692292
TI  - A new MRI approach for accurately implanting microelectrodes into deep brain
      structures of the rhesus monkey (Macaca mulatta).
AB  - The accurate implantation of microelectrodes is a significant difficulty facing
      many neurophysiologists. This paper reports on a new method used to promote the
      precise positioning of electrode implantation through magnetic resonance imaging
      (MRI), allowing both the relevant brain structure and the MRI-visible external
      markers anchored on the skull (in this case rigid glass tubes with a 0.5mm
      internal diameter) to be displayed. By referencing these markers, the coordinates
      of the brain target were calculated. Using this novel approach, recording
      electrodes were successfully implanted into the superior colliculus (SC) of
      rhesus monkeys, with an error <1mm, and its neuronal discharge signals were
      obtained. This new method allows neurophysiologists to precisely target the small
      deep brain structures of monkeys and study their electrophysiological
      characteristics in detail.

PMID- 20692293
TI  - Spinal cord integrity monitoring by adaptive coherence measurement.
AB  - OBJECTIVE: Injury during routine spinal cord procedures could result in
      devastating consequences for the surgical patient. Spinal cord monitoring through
      somatosensory evoked potentials (SEPs) remains a viable method for prevention of
      serious injury. METHODS: The adaptive coherence estimation (ACE) is a method to
      iteratively calculate signal match quality through successive filter entrainment.
      Here we compare the speed of detection with ACE to conventional amplitude
      measurements. Both absolute magnitude of ACE and amplitude as well as slope
      change detector algorithm (Farley-Hinich) was run as well to determine the
      earliest time when a significant change occurred. RESULTS: The standard error for
      the ACE algorithm is close to one tenth of the amplitude measure, Since the ACE
      algorithm achieved low variance during baseline measurement, we were able to
      achieve rapid detection of injury. For absolute magnitude detection ACE was
      faster than amplitude for the 20 g injury weight class. It took an average of 10
      epochs to detect the injury with adaptive coherence and nearly 19 with standard
      amplitude metrics using absolute magnitude changes. Abrupt change detection
      methods using slope change show that ACE provides more favorable detection
      capabilities comparable to amplitude. Additionally, there was a significant
      increase in the ROC curve between ACE and amplitude alone (p<0.05). CONCLUSIONS:
      Because of its excellent detection capabilities, the adaptive coherence method
      provides an excellent supplement to traditional amplitude for capturing injury
      related changes in SEPs. SIGNIFICANCE: Adaptive coherence remains a viable method
      for rapidly and accurately detecting spinal injury.

PMID- 20692294
TI  - Comparing levels of biochemical markers in CSF from cannulated and non-cannulated
      rats.
AB  - Cerebrospinal fluid (CSF) is commonly used for assessing biomarkers of drug
      efficacy or disease progression in the central nervous system. Studies of CSF
      from pre-clinical species can characterize biomarkers for use in clinical trials.
      However, obtaining CSF from pre-clinical species, particularly rodents, can be
      challenging due to small body sizes, and consequently, low volumes of CSF.
      Surgical cannulation of rats is commonly used to allow for CSF withdrawal from
      the cisterna magna. However, cannulae do not remain patent over multiple days,
      making chronic studies on the same rats difficult. Moreover, CSF biomarkers may
      be affected by cannulation. Thus cannulation may contribute confounding factors
      to the understanding of CSF biomarkers. To determine the potential impact on
      biomarkers, CSF was analyzed from cannulated rats, surgically implanted with
      catheters as well as from non-cannulated rats. Brain protein biomarkers (alphaII
      spectrin SBDP150 and total tau) and albumin, were measured in the CSF using ELISA
      assays. Overall, cannulated rat CSF had elevated levels of the biomarkers
      examined compared to non-cannulated rat CSF. Additionally, the variation in
      biomarker levels observed among CSF from cannulated rats was greater than that
      observed for non-cannulated rat CSF. These results demonstrate that in some
      cases, biomarker assessment using CSF from cannulated rats may differ from that
      of non-cannulated animals and may contribute confounding factors to biomarker
      measurements and assay development for clinical use.

PMID- 20692295
TI  - Trends in transmitted drug-resistant HIV-1 and demographic characteristics of
      newly diagnosed patients: nationwide surveillance from 2003 to 2008 in Japan.
AB  - The emergence and transmission of drug-resistant human immunodeficiency virus-1
      (HIV-1) compromises antiretroviral treatment for HIV-1. Thus, testing for drug
      resistance is recommended at diagnosis and before initiating highly active
      antiretroviral treatment. We conducted an epidemiological study enrolling newly
      diagnosed patients between 2003 and 2008 in our nationwide surveillance network.
      In the 6-year study period, the prevalence of drug-resistant HIV-1 among 2573
      patients, consisting mainly of Japanese men in their late-30s and infected
      through male-to-male sexual contacts, followed an increasing trend from 5.9%
      (16/273) in 2003 to 8.3% (50/605) in 2008. Nucleoside reverse transcriptase
      inhibitor-associated mutations predominated in each year, with T215 revertants
      being the most abundant. The predictive factor for drug-resistant HIV-1
      transmission was subtype B (OR=2.36; p=0.004), and those for recent HIV-1
      infection were male gender (OR=3.79; p=0.009), MSM behavior (OR=1.67; p=0.01),
      Japanese nationality (OR=2.31; p=0.008), and subtype B (OR=5.64; p<0.05).
      Continued activities are needed to raise awareness of the risks of HIV-1
      infection and complications of drug-resistant strains. Continued surveillance is
      also needed to understand trends in the HIV-1 epidemic.

PMID- 20692296
TI  - Antinociception and sedation following intracerebroventricular administration of
      Delta9-tetrahydrocannabinol in female vs. male rats.
AB  - Systemically administered cannabinoids produce greater antinociceptive and
      sedative effects in female compared to male rats. Sex differences in the brain
      endocannabinoid system have also been reported. The aim of this study was to
      determine whether sex differences in antinociceptive and motoric effects of a
      cannabinoid can be attributed to supraspinal mechanisms. Vehicle or Delta9
      tetrahydrocannabinol (THC, 100 MUg) was administered i.c.v., and behavioral
      effects were compared between gonadally intact male and female rats, and among
      females in different estrous stages (early proestrus, late proestrus, estrus and
      diestrus). Antinociception on the tail withdrawal and paw pressure tests after
      i.c.v. THC was slightly but not significantly greater in females (pooled across
      estrous stages) compared to males. THC suppressed locomotor activity similarly in
      all groups, with the exception that only males showed hyperlocomotion at 4 h post
      injection. When females in the four estrous stages were compared, females in late
      proestrus showed significantly greater THC-induced antinociception than females
      in estrus (and males). These results suggest that supraspinal mechanisms may
      contribute to greater systemic THC effects in females compared to males, and to
      estrous stage-dependent differences in THC effects among females.

PMID- 20692297
TI  - Studies on the structural mucins of the Echinococcus granulosus laminated layer.
AB  - The larvae of the cestodes belonging to the genus Echinococcus are outwardly
      protected by the laminated layer (LL), a crucial but poorly understood
      carbohydrate-rich acellular structure. Carbohydrate structural data strongly
      suggest that the main components of the LL are mucins. The most massive LL in the
      genus is featured by E. granulosus, agent of cystic hydatid disease. No
      appropriate methods existed to date for the solubilisation of the E. granulosus
      LL and the electrophoretic visualisation of its proposed structural mucins. We
      report that reduction of disulphides greatly aids LL disassembly, resulting in
      almost full solubilisation in combination with moderate sonication. The
      structural mucins can then be visualised by agarose electrophoresis and blotting
      with galactose-binding lectins, which also react strongly with the LL in tissue
      sections. A substantial portion of the material migrates as if positively
      charged; since the LL glycans are neutral, this may correspond to mucins with
      cationic peptide backbones.

PMID- 20692298
TI  - Transduction of Schistosoma japonicum schistosomules with vesicular stomatitis
      virus glycoprotein pseudotyped murine leukemia retrovirus and expression of
      reporter human telomerase reverse transcriptase in the transgenic schistosomes.
AB  - Although draft genome sequences of two of the major human schistosomes,
      Schistosoma japonicum and Schistosoma mansoni are available, the structures and
      characteristics of most genes and the influence of exogenous genes on the
      metabolism of schistosomes remain uncharacterized. Furthermore, which functional
      genomics approaches will be tractable for schistosomes are not yet apparent.
      Here, the vesicular stomatitis virus glycoprotein (VSVG)-pseudotyped pantropic
      retroviral vector pBABE-puro was modified to incorporate the human telomerase
      reverse transcriptase gene (hTERT) as a reporter, under the control of the
      retroviral long terminal repeat (LTR). Pseudotyped virions were employed to
      transduce S. japonicum to investigate the utility of retrovirus-mediated
      transgenesis of S. japonicum and the activity of human telomerase reverse
      transcriptase as a reporter transgene in schistosomes. Schistosomules perfused
      from experimentally infected rabbits were cultured for 6 days after exposure to
      the virions after which genomic DNAs from virus exposed and control worms were
      extracted. Analysis of RNA from transduced parasites and immunohistochemistry of
      thin parasite sections revealed expression of hTERT in the transduced worms.
      Expression of hTERT was also confirmed by immunoblot analysis. These findings
      indicated that S. japonicum could be effectively transduced by VSVG-pseudotyped
      retrovirus carrying the hTERT gene. Given the potential of hTERT to aid in
      derivation of immortalized cells, these findings suggest that this pantropic
      retroviral approach can be employed to transduce cells from specific tissues and
      organs of schistosomes to investigate the influence of transgene hTERT on growth
      and proliferation of schistosome cells.

PMID- 20692299
TI  - Further studies on the effects of intracrine and extracellular angiotensin II on
      the regulation of heart cell volume. On the influence of aldosterone and
      spironolactone.
AB  - The influence of extracellular and intracellular angiotensin II (Ang II) on the
      cell volume in the failing heart of cardiomyopathic hamsters (TO2) was further
      investigated as well as the influence of aldosterone and spironolactone on the
      Ang II action on cell volume. Measurements of cell width and area of quiescent
      ventricular cardiomyocytes were performed using a video camera and computer
      analysis and the relative cell volume was calculated. All measurements of cell
      volume were performed in the same cell before and after the administration of Ang
      II (10-8M). The results indicated that: a) the increase in cell volume caused by
      extracellular Ang II(10-8 M) was enhanced in cells incubated with aldosterone
      (100 nM) for 48 h; b) the effect of aldosterone was abolished by spironolactone
      (10-8 M); c) the decline in cell volume elicited by intracellular administration
      of Ang II (10-8 M) was increased by aldosterone and inhibited by spironolactone;
      d) the effects of aldosterone and spironolactone were related, in part, to a
      change in expression of AT1 receptors; and e) the intracellular administration of
      Ang II reduced the swelling-dependent chloride current (I(Clswell)). The
      implications of these findings to the failing heart and myocardial ischemia are
      discussed.

PMID- 20692300
TI  - Angiotensin-converting enzymes (ACE and ACE2) are downregulated in renal tumors.
AB  - The angiotensin-converting enzymes (ACE and ACE2) are highly expressed in renal
      tubules and play an important role in the regulation of renal function by the
      intrarenal renin-angiotensin system (iRAS). Dysregulation of these cell-surface
      peptidases has been associated with renal injury. Most of these studies, however,
      have focused on non-neoplastic kidney diseases. In the present study, ACE and
      ACE2 activity and protein and mRNA expression were analysed in a subset of clear
      cell (CCRCC) and chromophobe (ChRCC) renal cell carcinomas, and in renal
      oncocytoma (RO). Enzyme activity was measured by spectrofluorometric (ACE2) and
      spectrophotometric assays (ACE), and protein and mRNA expression were determined
      by immunohistochemistry and qRT-PCR assays, respectively. The enzyme activities
      and immunohistochemistry showed that both enzymes are mainly downregulated in
      these neoplasms. qRT-PCR studies in CCRCC showed no positive correlation between
      ACE and ACE2 activity/protein expression and mRNA levels, whereas downregulation
      of ACE2 mRNA levels was observed in tumors from the distal nephron (ChRCC and
      RO). These findings suggest a metabolic imbalance in iRAS and a role of this
      system in renal neoplastic diseases, and point to ACE and ACE2 as potential
      prognostic/diagnostic markers.

PMID- 20692301
TI  - Short sleeping time and psychobiological responses to acute stress.
AB  - The aim of this study was to examine the association between self-reported
      sleeping time and psychobiological stress responses [3-Methoxy-4
      hydroxyphenylglycol (MHPG) and Secretory immunoglobulin A (IgA), perceived stress
      responses]. Thirty seven healthy men and women were recruited, and participants
      were divided according to the habitual number of hours of sleep as follows:
      adequate sleepers (AS) (6-8h sleep per night regularly) (N=22) and short sleepers
      (SS) (less than 5h sleep per night regularly) (N=15). Salivary MHPG, s-IgA and
      perceived stress were measured at baseline, immediately after task and recovery
      period. An increase in free-MHPG during the task period was observed in AS
      although free-MHPG increased only after the task period in SS. The level of s-IgA
      in both groups significantly increased during the task period, and quickly
      returned to a basal level during the recovery period. The results show that less
      than 5h of sleep was associated with different responsiveness to the Stroop color
      word conflict task compared to sufficient sleep, especially in the NA system.

PMID- 20692302
TI  - Behavioral and gene expression analyses in heterozygous XBP1 knockout mice:
      Possible contribution of chromosome 11qA1 locus to prepulse inhibition.
AB  - The Xbp1 gene, located on chromosome 11qA1 in Mus musculus, encodes a key
      transcription factor in the endoplasmic reticulum stress response pathway. XBP1
      play a role in brain development and implicated in pathogenesis of
      neurodegenerative and psychiatric diseases. To evaluate the role of Xbp1 in
      behavioral phenotypes, we subjected heterozygous Xbp1 knockout (Xbp1+/-) mice to
      a battery of behavioral tests. Xbp1+/- mice showed enhanced prepulse inhibition
      (PPI). We also examined gene expression profiles in frontal cortex and
      hippocampus of Xbp1+/- mice to investigate the molecular basis that could
      underlie behavioral phenotypes. Gene expression analysis showed that several
      genes located on chromosome 11qA1 were differentially expressed. Among them,
      Uqcr10 and Nipsnap1 were strongly up-regulated. Significant up-regulation of
      these genes in 129S compared with BALB/c as well as higher PPI in 129S than
      BALB/c was previously reported. The ES cells used to generation of XBP1 knockout
      mice were derived from 129S and the founder was backcrossed with BALB/c. Thus,
      these findings would be accounted for by 129S-derived chromosomal region flanking
      Xbp1. These results support the contribution of chromosome 11qA1 locus to the
      amount of PPI. Uqcr10 and Nipsnap1 are good candidate genes that could impact
      PPI.

PMID- 20692303
TI  - Production of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) in recombinant
      Corynebacterium glutamicum using propionate as a precursor.
AB  - Lipopolysaccharides free P[3-hydroxybutyrate (3HB)-co-3-hydroxyvalerate (3HV)]
      production was achieved using recombinant Corynebacterium glutamicum harboring
      polyhydroxyalkanoate (PHA) biosynthetic genes from Ralstonia eutropha. Cells
      grown on glucose with feeding of propionate as a precursor of 3HV unit
      accumulated 8-47wt% of P(3HB-co-3HV). The 3HV fraction in the copolymer was
      varied from 0 to 28mol% depending on the propionate concentrations.

PMID- 20692304
TI  - The structural biology of PRRSV.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) is an enveloped,
      positive-sense single-stranded RNA virus belonging to the Arteriviridae family.
      Arteriviruses and coronaviruses are grouped together in the order Nidovirales,
      based on similarities in genome organization and expression strategy. Over the
      past decade, crystal structures of several viral proteins, electron microscopic
      studies of the virion, as well as biochemical and in vivo studies on protein
      protein interactions have led to a greatly increased understanding of PRRSV
      structural biology. At this point, crystal structures are available for the viral
      proteases NSP1alpha, NSP1beta and NSP4 and the nucleocapsid protein, N. The
      NSP1alpha and NSP1beta structures have revealed additional non-protease domains
      that may be involved in modulation of host functions. The N protein forms a dimer
      with a novel fold so far only seen in PRRSV and other nidoviruses. Cryo-electron
      tomographic studies have shown the three-dimensional organization of the PRRSV
      virion and suggest that the viral nucleocapsid has an asymmetric, linear
      arrangement, rather than the isometric core previously described. Together, these
      studies have revealed a closer structural relationship between arteri- and
      coronaviruses than previously anticipated.

PMID- 20692305
TI  - Alphavirus vectors for cancer therapy.
AB  - Alphaviruses contain a single strand RNA genome that can be easily modified to
      express heterologous genes at very high levels in a broad variety of cells,
      including tumor cells. Alphavirus vectors can be used as viral particles
      containing a packaged vector RNA, or directly as nucleic acids in the form of RNA
      or DNA. In the latter case alphavirus RNA is cloned within a DNA vector
      downstream of a eukaryotic promoter. Expression mediated by these vectors is
      generally transient due to the induction of apoptosis. The high expression
      levels, induction of apoptosis, and activation of type I IFN response are the key
      features that have made alphavirus vectors very attractive for cancer treatment
      and vaccination. Alphavirus vectors have been successfully used as vaccines to
      induce protective and therapeutic immune responses against many tumor-associated
      antigens in animal models of mastocytoma, melanoma, mammary, prostate, and
      virally induced tumors. Alphavirus vectors have also shown a high antitumoral
      efficacy by expressing antitumoral molecules in tumor cells, which include
      cytokines, antiangiogenic factors or toxic proteins. In these studies induction
      of apoptosis in tumor cells contributed to the antitumoral efficacy by the
      release of tumor antigens that can be uptaken by antigen presenting cells,
      enhancing immune responses against tumors. The potential use of alphaviruses as
      oncolytic agents has also been evaluated for avirulent strains of Semliki Forest
      virus and Sindbis virus. The fact that this latter virus has a natural tropism
      for tumor cells has led to many studies in which this vector was able to reach
      metastatic tumors when administered systemically. Other "artificial" strategies
      to increase the tropism of alphavirus for tumors have also been evaluated and
      will be discussed.

PMID- 20692306
TI  - Porcine reproductive and respiratory syndrome virus (PRRSV) could be sensed by
      professional beta interferon-producing system and had mechanisms to inhibit this
      action in MARC-145 cells.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) causes an
      economically important disease in swine-producing area, and interferon beta (IFN
      beta) is the first responder against the animal virus infection. However, whether
      PRRSV could induce the production of IFN-beta is controversial. In this paper, we
      first time found that PRRSV could phosphorylate IFN-regulatory factor 3 (IRF-3)
      and weakly activate the IFN-beta promoter in MARC-145 cells in early infection,
      but the activations of IRF-3 and IFN-beta promoter were rapidly inhibited in the
      following infection. Furthermore, which components or products of the invading
      PRRSV cause PRRSV to inhibit IFN-beta promoter activity attracted our attentions.
      The obtained results showed that PRRSV nsp1 could inhibit Poly(I:C)-induced IFN
      beta promoter activity in MARC-145 cells by down-regulating the protein level of
      IRF-3 and inhibiting the phosphorylation of IRF-3. In conclusion, our results
      suggested that PRRSV could be sensed by professional IFN-beta-producing system
      and had mechanisms to inhibit this action in MARC-145 cells.

PMID- 20692307
TI  - Dose sparing enabled by skin immunization with influenza virus-like particle
      vaccine using microneedles.
AB  - To address the limitations of conventional influenza vaccine manufacturing and
      delivery, this study investigated administration of virus-like particle (VLP)
      influenza vaccine using a microneedle patch. The goal was to determine if skin
      immunization with influenza VLP vaccine using microneedles enables dose sparing.
      We found that low-dose influenza (A/PR/8/34 H1N1) VLP vaccination using
      microneedles was more immunogenic than low-dose intramuscular (IM) vaccination
      and similarly immunogenic as high-dose IM vaccination in a mouse model. With a
      1MUg dose of vaccine, both routes showed similar immune responses and protective
      efficacy, with microneedle vaccination being more effective in inducing recall
      antibody responses in lungs and antibody secreting cells in bone marrow. With a
      low dose of vaccine (0.3MUg), microneedle vaccination induced significantly
      superior protective immunity, which included binding and functional antibodies as
      well as complete protection against a high dose lethal infection with A/PR/8/34
      virus, whereas IM immunization provided only partial (40%) protection. Therefore,
      this study demonstrates that microneedle vaccination in the skin confers more
      effective protective immunity at a lower dose, thus providing vaccine dose
      sparing effects.

PMID- 20692308
TI  - A simple method to achieve high doxorubicin loading in biodegradable
      polymersomes.
AB  - Doxorubicin (Dox), an anthracycline anticancer drug, was successfully
      incorporated into block copolymer vesicles of poly(trimethylene carbonate)-b
      poly(L-glutamic acid) (PTMC-b-PGA) by a solvent-displacement (nanoprecipitation)
      method. pH conditions were shown to have a strong influence on loading capacity
      and release profiles. Substantial drug loading (47% w/w) was achieved at pH 10.5.
      After pH neutralization, aqueous dispersions of drug-loaded vesicles were found
      stable for a prolonged period of time (at least 6months) without vesicle
      disruption or drug precipitation. Dox-loaded vesicles exhibited in vitro pH and
      temperature-dependent drug release profiles: release kinetics fastened in acid
      conditions or by increasing temperature. These features strongly support the
      interest of developing PTMC-b-PGA polymersomes as carriers for the controlled
      delivery of Dox.

PMID- 20692309
TI  - Focused ultrasound for targeted nanoparticle delivery to tumors.

PMID- 20692310
TI  - Task-based nutrition labelling.
AB  - Task-based interface design principles (TBI) were evaluated as a framework for
      designing effective nutritional labels. In two experiments a total of 123 people
      assembled a packed lunch, selecting components using labels in GDA or TBI format,
      or when given only the names of the foods. Study 1 found that a GDA label helped
      people make healthier choices than the product name alone, but that for a number
      of types of food, most people would make the same decision with or without a GDA
      label. Moreover, decisions were much faster when made with the name alone. Study
      2 introduced a TBI label in the context of the more specific task of keeping the
      salt in the lunch under 1g. TBI and GDA labels reduced salt equally, but only the
      TBI label was as quick as the name alone. Labels that are aligned with people's
      specific objectives are more efficient. TBI is a potentially useful framework,
      that can be deployed using mobile computing.

PMID- 20692311
TI  - Substance P (SP) and vasoactive intestinal polypeptide (VIP) in the lower uterine
      segment in first and repeated cesarean sections.
AB  - The authors studied the presence of substance P (SP) and vasoactive intestinal
      polypeptide (VIP) and their related fibers in the lower uterine segment (LUS) in
      133 women undergoing cesarean sections (CS) during active labor. These were
      divided into 2 groups: women undergoing repeat or first CSs. Specimens were
      collected from the LUS and were evaluated by light microscopy and by
      immunohistochemistry, for the morphometrical quantification of the SP and VIP
      fibers in the LUS. The SP amount was higher in the post-CS scar, while the VIP
      amount decreased: nerve fibers contained an SP amount of up to 13 +/- 2.6C.U.,
      while nerve fibers contained a VIP amount of up to 7 +/- 1.9 C.U. The SP amount
      counts 10 +/- 1.5% of the total Bodian fibers, and the ratio of the VIP is 10 +/-
      1.8% of their total amount. In normal conditions only 6.61 C.U. of the Bodian
      surface is occupied by SP related nerve fibers in contrast to 6.63 C.U. of the
      total surface by VIP; the amount of SP increased up to 13 +/- 2.6C.U., while it
      decreased in the LUS previous scars. The SP levels are higher in repeat CS, while
      the VIP levels are reduced in the LUS. The increase of SP is probably linked to
      the attempt to achieve cervical ripening in a post-CS LUS, with the possible
      consequences of dystocia during vaginal birth after CS. Nevertheless, the
      decrease of VIP probably affects the relaxation of the internal uterine orifice,
      compromising the LUS formation and cervical ripening.

PMID- 20692312
TI  - Hydroquinone PBPK model refinement and application to dermal exposure.
AB  - A physiologically based pharmacokinetic (PBPK) model for hydroquinone (HQ) was
      refined to include an expanded description of HQ-glucuronide metabolites and a
      description of dermal exposures to support route-to-route and cross-species
      extrapolation. Total urinary excretion of metabolites from in vivo rat dermal
      exposures was used to estimate a percutaneous permeability coefficient (K(p);
      3.6*10(-5) cm/h). The human in vivo K(p) was estimated to be 1.62*10(-4) cm/h,
      based on in vitro skin permeability data in rats and humans and rat in vivo
      values. The projected total multi-substituted glutathione (which was used as an
      internal dose surrogate for the toxic glutathione metabolites) was modeled
      following an exposure scenario based on submersion of both hands in a 5% aqueous
      solution of HQ (similar to black and white photographic developing solution) for
      2 h, a worst-case exposure scenario. Total multi-substituted glutathione
      following this human dermal exposure scenario was several orders of magnitude
      lower than the internal total glutathione conjugates in rats following an oral
      exposure to the rat NOEL of 20 mg/kg. Thus, under more realistic human dermal
      exposure conditions, it is unlikely that toxic glutathione conjugates (primarily
      the di- and, to a lesser degree, the tri-glutathione conjugate) will reach
      significant levels in target tissues.

PMID- 20692313
TI  - Polychlorinated biphenyls (PCBs) contamination and aryl hydrocarbon receptor
      (AhR) agonist activity of Omega-3 polyunsaturated fatty acid supplements:
      implications for daily intake of dioxins and PCBs.
AB  - Omega-3 polyunsaturated fatty acid (n-3 PUFA) rich oils derived primarily from
      fish are frequently consumed as supplements. Due to the tendency of persistent
      organic pollutants (POPs) to accumulate in exposed organisms, n-3 PUFA
      supplements can contain sufficient POPs to present a risk to consumers. Here we
      investigated PCB concentrations and aryl hydrocarbon receptor (AhR) agonist
      activity in 17 n-3 PUFA supplements available in Canada. PCBs ranged from <0.8 to
      793 ng g(-1) oil, with salmon- and seal-derived products yielding the highest
      values. AhR agonist activity from a reporter gene assay ranged from 1.3 to 72.2
      pg TEQ g(-1) oil, with salmon and tuna yielding the highest values. When consumed
      at the recommended doses and as a supplement to the average Canadian diet, seal
      derived oil can contribute to exceedance of the tolerable daily intake of 20 ng
      PCBs kg-BW(-1)day(-1), and salmon-, tuna-, and sea herring-derived oils can
      contribute to exceedance of the tolerable daily intake limit of 2.3 pg TEQ kg-BW(
      1)day(-1). The beneficial properties of fish and n-3 PUFA supplements, and the
      results of this study suggest that it is prudent to consume supplements derived
      from small, cold-water fatty fish. Further research will be necessary to draw
      firm conclusions.

PMID- 20692314
TI  - Safety assessment of Cordyceps guangdongensis.
AB  - Cordyceps guangdongensis as a kind of fungus, has been discovered and cultivated
      successfully in recent years. However, its safety assessments have not been
      studied. In this report, a serial of tests for toxicological safety assessments
      were depicted in details. These tests included bacterial reverse mutation (Ames)
      study, bone marrow cell micronucleus test in mice, sperm aberration test in mice,
      teratogenicaction test in rats, acute toxicity test and 13-week oral toxicity
      study in rats. After a profound analysis of these tests, it clearly demonstrated
      that C. guangdongensis did not have any mutagenic, clastogenic nor genotoxic
      effects; the oral LD50 of the biomass in rats was greater than 15 g/kg body
      weight; the no-observed adverse-effect-levels (NOAEL) was 5.33 g/kg body weight
      according to the 13-week oral toxicity analysis. Therefore, a conclusion can be
      drawn that C. guangdongensis is considered safe for long term consumption.

PMID- 20692315
TI  - Evaluating the accumulation of arsenic in maize (Zea mays L.) plants from its
      growing media by cloud point extraction.
AB  - A cloud point extraction has been developed for the determination of As in maize
      (Zea mays L.) and adjoining agriculture soil. The different parts of maize
      (grains, shoots and roots) and soil were subjected to microwave assisted
      digestion in a mixture of nitric acid and hydrogen peroxide (2:1 ratio). The
      trace amounts of As was pre-concentrated by cloud point extraction, as prior step
      to its determination by electrothermal atomic absorption spectrometry. The main
      factors affecting cloud point extraction efficiency, such as pH of sample
      solution, concentration of ammonium pyrrolidine dithiocarbamate and Triton X-114,
      equilibration temperature and time period for shaking were investigated in
      detail. For validation of proposed method a certified reference material of whole
      meal flour BCR 189 was used. No significant difference p>0.05 was observed
      between the experimental results and the certified values of CRM (paired t-test).
      The translocation of total As in different parts of maize were found in the order
      of, Root>Shoot>Grain.

PMID- 20692317
TI  - Comparative assessment of the sensory irritation potency in mice and rats nose
      only exposed to ammonia in dry and humidified atmospheres.
AB  - Young adult male Wistar rats, a species commonly used in inhalation toxicity
      studies, and OF1 mice, a species often used in sensory irritation studies, were
      simultaneously nose-only exposed for 45-min to ammonia in concentrations from 92
      to 1243 mg/m(3). This study examined airway reflexes by the changes in
      respiratory patterns elicited by ammonia in either dry, steam-humidified
      (approximately 95% relative humidity) or aqueous aerosol containing atmospheres.
      This served the objective to explore whether high concentrations of anhydrous
      ammonia and/or high humidity and aqueous aerosol change the predominant nasal
      deposition site to more distal locations in the lung. Animals from all groups
      tolerated the exposure without evidence of respiratory tract irritation, changes
      in body and lung weights. The evoked changes on breathing patterns resembled
      those known to occur following exposure to 'upper respiratory tract sensory
      irritants', rapid in onset and reversibility. Reflex stimulation from the lower
      airways was not observed in any group. While mice showed some adaption during the
      45-min exposure period, rats displayed more stable changes in respiratory
      patterns. In this species humidity- or aqueous aerosol-related changes in sensory
      irritation potency did not occur to any appreciable extent. The respiratory
      decrease 50%, RD(50), was 972 and 905 mg/m(3) in dry and wet air, respectively.
      In contrast, mice appeared to more susceptible to ammonia in presence of dry air
      (the RD(50), was 582 and 732 mg/m(3) in dry and wet air, respectively). In
      summary, it was shown that the sensory irritation potency of ammonia does not
      increase when inhaling wet atmospheres nor penetrates this gas into the lower
      airways up to 1243 mg/m(3)*45-min. The mild-to-moderate sensory irritation
      related effects observed at ~ 400 mg/m(3) (571 ppm)*45-min do not appear to be
      offensive enough to impair escape as a result of upper airway sensations.
      Interestingly, this rat-based estimate matches almost exactly the experienced
      based RAM TRAC recommendations of 696 and 492 ppm for 30 and 60 min,
      respectively.

PMID- 20692318
TI  - Effect of pH on tooth discoloration from food colorant in vitro.
AB  - OBJECTIVES: The purpose of this study was to evaluate the effect of acidic,
      neutral and alkaline food colorant media (FCM) on tooth discoloration in vitro.
      METHODS: Treatment (n=24) and control (n=24) sterile, hydrated human molars were
      prepared in individual, impervious holders and their color measured (pretest)
      using a non-contact spectroradiometer system. Specimens were randomly assigned to
      and immersed in one of the three buffer solutions (pH 2, pH 7 or pH 12). Red food
      color (Red 40) was added to the treatment buffer solutions at 0.025%. Immersed
      specimens were incubated for 4h at 37 degrees C. Color was also measured after
      immersion/incubation (posttest) and again after subsequent 2-min of polish using
      plain-pumice slurry with a slow-speed handpiece (post-polish). Differences in CIE
      a* (redness parameter) were analyzed by repeated measures ANOVA with Bonferroni
      corrected t-tests for the pairwise comparisons of interest. RESULTS: Tooth
      discoloration was measured as total stain (mean difference in a* between posttest
      minus pretest), extrinsic stain (mean difference in a* post-polish minus
      posttest) and intrinsic stain (mean difference in a* post-polish minus pretest).
      No significant change in color was observed between the control and treatment
      groups for neutral and alkaline FCM. However, acidic FCM caused reddish tooth
      discoloration posttest minus pretest, post-polish minus pretest and post-polish
      minus posttest compared to neutral and alkaline treatment and control groups.
      CONCLUSIONS: The degree and type of tooth discoloration are influenced by both
      the low pH and food color rather than the dietary pigment alone.

PMID- 20692319
TI  - CC-chemokine MIP-1alpha in the spinal cord contributes to nerve injury-induced
      neuropathic pain.
AB  - We investigated the involvement of spinal macrophage inflammatory protein-1alpha
      (MIP-1alpha), an inflammatory chemokine, in partial sciatic nerve ligation (PSL)
      induced neuropathic pain in mice. PSL increased MIP-1alpha mRNA levels as well as
      levels of the MIP-1alpha receptor, CCR1, but not CCR5 in the spinal dorsal horn.
      PSL-induced tactile allodynia and thermal hyperalgesia were prevented by
      intrathecal (i.t.) injection of a neutralizing antibody of MIP-1alpha (2ng).
      Recombinant MIP-1alpha (10pmol, i.t.) elicited long-lasting tactile allodynia and
      thermal hyperalgesia in naive mice. These results suggest that peripheral nerve
      injury elicits the up-regulation of spinal MIP-1alpha and CCR1 to participate in
      neuropathic pain.

PMID- 20692320
TI  - Presynaptic dopaminergic agonists increased gripping-generated immobility
      episodes in the myelin-mutant taiep rat.
AB  - The taiep rat is a myelin mutant whose immobility episodes (IEs) can be caused by
      gripping them by the tail. Electroencephalographic recordings during IEs show a
      rapid-eye movement sleep-like pattern, similar to narcolepsy-cataplexy in
      canines. Systemic administration of alpha(2)-adrenoceptor agonists and the
      alpha(1) antagonist increase gripping-generated IEs. Furthermore, adrenergic
      alpha(2) antagonists decrease them. Serotonin receptors are also involved in the
      regulation of IEs, because the 5-HT(1A)-5-HT(1B) serotonin-receptor agonists
      decrease the IE frequency, as do the postsynaptic-serotonergic 5-HT(2A-2C)
      agonists. The rats were maintained under standard conditions with a 12:12h
      light:dark cycle, lights on at 0700, with free access to rodent pellets and tap
      water. Drugs were freshly prepared using sterile water and administered
      intraperitoneally at 0800 with the observation lasting 90 min. The IEs were
      caused by gripping the rat's tail every 5 min. Systemic injection of (-)
      quinpirole, R(+)-7-hydroxy-2-(dipropylamino)tetralin (7-OH-DPAT), or trans-(+/-)
      3,4,4a,10b-Tetrahydro-4-propyl-2H,5H-[1]benzopyrano[4,3-b]-1,4-oxazin-9-ol ((+/-)
      PD 128,907) increased both the frequency and mean duration of the IEs. The IEs
      produced by (-)-quinpirole were blocked by the previous administration of (-)
      sulpiride and those by 7-OH-DPAT were blocked by tiapride. Systemic injection of
      sulpiride reduced gripping-generated IEs, but not the changes with either
      tiapride or U-99194, two other antagonists. In canine narcolepsy, systemic
      administration of D(2)-dopaminergic agonists increases the frequency of
      cataplexies and decreased them by using (-)-sulpiride similar to the
      pharmacological profile in taiep cataplexies. Because of this evidence, we
      proposed taiep rats as an adequate model of this sleep illness and for the
      evaluation of anticataplexic drugs.

PMID- 20692321
TI  - Vision enhances selective attention to body-related information.
AB  - Viewing ones' own hands while directing attention to one of the hands leads to
      earlier attentional modulations of somatosensory processing than when hands are
      not visible. This effect of vision on tactile-spatial selection could be
      explained by vision providing additional information about the location of the
      hands in external space. The present study investigated whether vision of the
      hands also affected tactile-attentional mechanisms when the relative locations of
      the hands were irrelevant. Participants silently counted infrequent tactile or
      auditory deviants in an alternating stream of tactile and auditory stimuli while
      ignoring stimuli in the other modality, when their hands were either visible or
      covered from view. Modality-selective attentional modulations of ERPs to tactile
      stimuli (when touches vs. tones were attended) were already present for the time
      range of the N80 component when hands were visible, but there were only later
      modulations (starting at N140) when hands were covered. This suggests that,
      rather than being restricted to tasks requiring spatial selection between body
      parts, vision of the hands can facilitate attention toward the body in far more
      general terms. In contrast to tactile stimuli, attentional modulations of ERPs to
      auditory stimuli (when tones vs. touches were attended) were not reliably
      affected by viewing the hands. This suggests that the primary purpose of visual
      facilitation may be to enhance the processing of body-related information only.

PMID- 20692322
TI  - Fluoxetine treatment induces dose dependent alterations in depression associated
      behavior and neural plasticity in female mice.
AB  - Antidepressant-induced increases in neurogenesis and neurotrophin mobilization in
      rodents and primates are proposed to be necessary for behavioral efficacy. The
      current study examines the relationship between the effects of fluoxetine
      treatment on behavior, cell proliferation and the neurotrophin BDNF in females.
      Female MRL/MpJ mice were treated acutely (5 and 10mg/kg) or chronically (2.5, 5
      and 10mg/kg b.i.d.) with fluoxetine and tested in the tail suspension test (TST)
      and or novelty-induced hypophagia test (NIH), respectively. Mice treated
      chronically with fluoxetine received 4 (100mg/kg) injections of 5-bromo-2'
      deoxyuridine (BrdU) on the last 4 days of treatment to measure DNA synthesis. The
      other half of the hippocampus and the frontal cortex was removed and examined for
      BDNF levels. Fluoxetine treatment decreased immobility in the TST and latency to
      eat in the NIH test, but only the highest dose of fluoxetine significantly
      altered behavior in both tests. Chronic treatment with 5 and 10mg/kg of
      fluoxetine significantly increased cell proliferation and BDNF levels in the
      hippocampus. Only chronic treatment with the highest of fluoxetine increased BDNF
      levels in the frontal cortex. Behavioral measures in the NIH test correlated with
      BDNF levels in the frontal cortex but not in the hippocampus or with cell
      proliferation in the hippocampus. These data suggest that females require high
      doses of fluoxetine for behavioral efficacy regardless of elevations of
      neurogenesis and BDNF mobilization in the hippocampus. Elevations in BDNF levels
      in the frontal cortex are related to the behavioral efficacy of fluoxetine.

PMID- 20692324
TI  - Event-related beta oscillations are affected by emotional eliciting stimuli.
AB  - According to previous results, negative emotional facial expressions elicit
      oscillatory beta responses. The present study analyzes event-related beta
      oscillations upon presentation of International Affective Picture System (IAPS)
      and aims to show whether behavior of beta in response to negative IAPS pictures
      also have similar dynamics. IAPS pictures (unpleasant, pleasant, and neutral)
      were presented as a block and random passive viewing to 14 healthy subjects (8
      male). Only with pictures with similar luminance level were selected as stimuli.
      Event-Related Potentials (ERPs) were recorded from 30 different scalp locations,
      and adaptive digital filtering was used for analysis in different frequency
      windows. The maximum peak-to-peak amplitudes were measured for each subject's
      averaged beta responses (15-30Hz) in the 0 and 300ms time window. Beta responses
      were significantly higher for unpleasant pictures than for pleasant and neutral
      pictures (average 50%). Beta responses were significantly higher for unpleasant
      than for pleasant pictures over frontal, central and parietal electrode sides
      (p<0.05). Furthermore, beta responses were significantly higher for unpleasant
      than for neutral pictures over parietal and occipital electrodes (p<0.04). In
      addition, the pleasant pictures elicited higher beta responses than neutral
      pictures over occipital electrode sites (p<0.04). The results of the present
      study indicate that negative emotions are related to increased beta responses in
      humans, independent of stimulus types (facial expression or IAPS pictures).
      Accordingly, beta responses to negative emotions are possibly a common
      phenomenon. The standardization of luminance in pictures may reduce divergences
      between results from different laboratories.

PMID- 20692323
TI  - Altered GABA(A) receptor subunit expression and pharmacology in human Angelman
      syndrome cortex.
AB  - The neurodevelopmental disorder Angelman syndrome is most frequently caused by
      deletion of the maternally derived chromosome 15q11-q13 region, which includes
      not only the causative UBE3A gene, but also the beta(3)-alpha(5)-gamma(3) GABA(A)
      receptor subunit gene cluster. GABAergic dysfunction has been hypothesized to
      contribute to the occurrence of epilepsy and cognitive and behavioral impairments
      in this condition. In the present study, analysis of GABA(A) receptor subunit
      expression and pharmacology was performed in cerebral cortex from four subjects
      with Angelman syndrome and compared to that from control tissue. The membrane
      fraction of frozen postmortem neocortical tissue was isolated and subjected to
      quantitative Western blot analysis. The ratios of beta(3)/beta(2) and
      alpha(5)/alpha(1) subunit protein expression in Angelman syndrome cortex were
      significantly decreased when compared with controls. An additional membrane
      fraction was injected into Xenopus oocytes, resulting in incorporation of the
      brain membrane vesicles with their associated receptors into the oocyte cellular
      membrane. Two-electrode voltage-clamp analysis of GABA(A) receptor currents was
      then performed. Studies of GABA(A) receptor pharmacology in Angelman syndrome
      cortex revealed increased current enhancement by the alpha(1)-selective
      benzodiazepine-site agonist zolpidem and by the barbiturate phenobarbital, while
      sensitivity to current inhibition by zinc was decreased. GABA(A) receptor
      affinity and modulation by neurosteroids were unchanged. This shift in GABA(A)
      receptor subunit expression and pharmacology in Angelman syndrome is consistent
      with impaired extrasynaptic but intact to augmented synaptic cortical GABAergic
      inhibition, which could contribute to the epileptic, behavioral, and cognitive
      phenotypes of the disorder.

PMID- 20692325
TI  - Two-item discrimination and Hamilton search learning in infant pigtailed macaque
      monkeys.
AB  - This study investigated how infant pigtailed macaque monkeys performed on two
      separate learning assessments, two-object discrimination/reversal and Hamilton
      search learning. Although the learning tasks have been tested on several species,
      including non-human primates, there have been no normative results reported for
      young macaque monkeys. The present study provides normative results for these
      learning tasks in very young captive pigtailed macaques and investigates the
      degree to which performances on these assessments are related. In addition, an
      error analysis was conducted to understand the choice patterns of the animals on
      each task. It was found that males took longer to reach criterion than females on
      the two-object reversal task. Performance and latency on the discrimination task
      predicted performance and latency on the reversal task. Performance on Hamilton
      Search Set-Breaking negatively predicted performance on the later Hamilton Search
      Forced Set-Breaking task. Finally, latency on reversal significantly predicted
      the latency on the Hamilton search task. These data provide strong evidence of a
      relationship between performance on discrimination and reversal. This study shows
      that, otherwise, each task assesses a different cognitive function.

PMID- 20692326
TI  - Taking phage integration to the next level as a genetic tool for mycobacteria.
AB  - Genes must be stably integrated into bacterial chromosomes for complementation of
      gene deletion mutants in animal infection experiments or to express antigens in
      vaccine strains. However, with currently available vectors it is cumbersome to
      create multiple, stable, unmarked chromosomal integrations in mycobacteria. Here,
      we have constructed a novel integration vector for mycobacteria that enables
      expression of genes from a cassette protected from transcriptional interference
      by bi-directional transcriptional terminators proven to be highly efficient in in
      vitro transcription termination assays. Removal of the integrase gene by a site
      specific recombinase, easily identifiable by loss of a backbone reporter gene,
      stabilizes the integration cassette and makes this vector ideally suitable for
      infection experiments. This integration vector can be easily adapted to different
      mycobacteriophage attachment sites (attB) due to its modular design. Integration
      of a gfp expression cassette at the L5, Giles and Ms6 attB sites in the
      chromosomes of Mycobacterium smegmatis and Mycobacterium tuberculosis yielded
      identical gfp expression levels, indicating that none of these sites are
      compromised for gene expression. The copy number of pAL5000-based
      extrachromosomal plasmids is 23 in M. smegmatis as determined by quantitative
      real-time PCR and accounts for the previously observed drastic reduction of gene
      expression upon integration of plasmids into the chromosome of mycobacteria. Gfp
      expression and fluorescence of M. smegmatis and M. tuberculosis strains with
      multiple integrations of gfp increased concomitantly with the copy number
      demonstrating that these vectors can be used to generate stronger phenotypes
      and/or to analyze several genes simultaneously in vivo.

PMID- 20692327
TI  - A novel liposomal vaccine improves humoral immunity and prevents tumor pulmonary
      metastasis in mice.
AB  - Basic fibroblast growth factor (bFGF) is an important stimulator of angiogenesis
      involving in neovascularization progression. The aim of this study is to evaluate
      whether a liposomal vaccine (MLB) based on xenogeneic human bFGF plus
      monophosphoryl lipid A (MPLA) could effectively induce cross-reaction immunity in
      mice and increase antitumor activity. Sera of mice were analyzed and IgG antibody
      titer in MLB group was obviously higher than other groups including the mice
      immunized with liposomal bFGF vaccine, bFGF plus Freund's adjuvant, empty
      liposome and PBS. Furthermore, tumor metastasis was significantly inhibited in
      MLB group, compared with L and PBS group. The IFN-gamma production of cultured
      splenocytes in vitro was evidently up-regulated meanwhile IL-4 production
      sustained in a low level, revealing that this vaccine stimulated Th1 immunity
      response preferentially. Taken together, these findings suggested that this novel
      bFGF vaccine could effectively induce humoral immunity through cross-reaction,
      mediate Th1 immune response preferentially and enhance antitumor activity in
      vivo.

PMID- 20692328
TI  - A comparison of skin delivery of ferulic acid and its derivatives: evaluation of
      their efficacy and safety.
AB  - Ferulic acid (FA) can be used as an antioxidant to prevent damage from
      ultraviolet (UV) radiation and skin carcinogenesis. To this end, the feasibility
      of the skin absorption of FA and its derivatives was evaluated in the present
      study. The percutaneous absorption of five compounds into/across porcine skin was
      measured and compared using Franz diffusion cells. The skin delivery from pH 6
      and 9.9 buffers was the highest for ferulic acid ethyl ether (FAEE), followed by
      coniferyl aldehyde (CD), coniferyl alcohol (CA), FA, and 3-hydroxy-4
      methoxycinnamic acid (HMA). The skin deposition and flux of FAEE with a pH 6
      buffer were 136 nmol/g and 26 nmol/cm(2)/h, respectively. No significant
      difference in permeation profiles was observed between the two pH buffers.
      According to permeation via the skin with different treatments (delipidization,
      ethanol, and oleic acid treatments), it was determined that the lipid bilayers in
      the stratum corneum (SC) comprised the predominant barrier for FA permeation. On
      the other hand, FAEE could easily partition into and penetrate across the skin
      through intercellular pathways. Nude mouse was used as an in vivo animal model to
      examine the amount of permeants remaining in the skin. The in vivo skin
      deposition was generally correlated with the in vitro results. The in vivo skin
      deposition of FAEE (145 nmol/g) was comparable to that of CD (150 nmol/g). The
      safety study which examined transepidermal water loss (TEWL), erythema, and the
      skin pH value demonstrated that the topical application of FA and related
      compounds for up to 24h did not cause skin irritation. It can be concluded that
      topical delivery may serve as an efficient and safe route for FA and its
      derivatives against photodamage.

PMID- 20692329
TI  - Identification of medicinal plants used as Tibetan Traditional Medicine jie-ji.
AB  - AIM OF THE STUDY: Based on the authors' collection of specimens used as jie-ji in
      local Tibetan areas, China, and taxonomic determination, this paper aims to give
      a list of medicinal plants as jie-ji, formally identify the ones recognized as
      jie-ji ga-bao or jie-ji na-bao and to offer basic data for further studies on
      these Tibetan herbs. MATERIALS AND METHODS: Local herbalists were visited in
      Tibetan areas, China to observe which plants were being used as jie-ji. Samples
      of the indigenous plants were collected at the same time. Also, the medicinal
      plants as jie-ji were taxonomically identified. RESULTS: A list of medicinal
      plants including 10 species of jie-ji in local Tibetan areas is given, including
      their morphological pictures used for identification. CONCLUSIONS: The origin of
      jie-ji is from 10 species of the Section Cruciata, Genus Gentiana (Gentianaceae).
      five species with dark blue flowers are used as jie-ji na-bao, the other five
      with white flowers are used as jie-ji ga-bao. Also, Gentiana macrophylla Pall.
      with dark blue flowers in the Section Cruciata, Genus Gentiana is not the
      original plant of jie-ji na-bao. The species endemic to the province are used as
      the original plants of jie-ji only in local Tibetan area of the province.
      Finally, the drug use of jie-ji in Traditional Tibetan Medicine is reasonable and
      it is efficacious.

PMID- 20692330
TI  - Neonatal exposure to bisphenol A reduces the pool of primordial follicles in the
      rat ovary.
AB  - We evaluated whether exposure to bisphenol A (BPA) disrupts neonatal follicle
      development in rats. From postnatal day 1 (PND1) to PND7, pups received corn oil
      (control), diethylstilbestrol (DES20: 20 MUg/kg-d, DES0.2: 0.2 MUg/kg-d), or BPA
      (BPA20: 20mg/kg-d, BPA0.05: 0.05 mg/kg-d). We examined follicular dynamics,
      multioocyte follicles (MOFs) incidence, proliferation and apoptosis rates,
      expression of steroid receptors (ERalpha, ERbeta, PR, AR) and cyclin-dependent
      kinase inhibitor 1B (p27) in PND8 ovaries. DES20, DES0.2 and BPA20-ovaries showed
      fewer primordial follicles and increased growing follicles. DES20-ovaries
      exhibited increased incidence of MOFs. Oocyte survival, AR, PR and apoptosis were
      not changed. Primordial and recruited follicles from BPA20-ovaries showed higher
      p27, whereas ERbeta and proliferation were both increased in recruited follicles.
      ERalpha positive primary follicles increased in BPA 20-ovaries. Results show that
      BPA reduces the primordial follicle pool by stimulating the neonatal initial
      recruitment, associated with an increased proliferation rate likely mediated by
      an estrogenic pathway.

PMID- 20692331
TI  - Chronic alcohol-induced liver injury and oxidant stress are decreased in
      cytochrome P4502E1 knockout mice and restored in humanized cytochrome P4502E1
      knock-in mice.
AB  - A major pathway for chronic ethanol-induced liver injury is ethanol-induced
      oxidant stress. Several pathways contribute to mechanisms by which ethanol
      induces oxidant stress. Although some studies support a role for cytochrome P450
      2E1 (CYP2E1), others do not. Most previous studies were conducted in the
      intragastric infusion model of ethanol administration. There is a need to develop
      oral models of significant liver injury and to evaluate the possible role of
      CYP2E1 in ethanol actions in such models. We evaluated chronic ethanol-induced
      liver injury, steatosis, and oxidant stress in wild-type (WT) mice, CYP2E1 knock
      out (KO) mice, and humanized CYP2E1 knock-in (KI) mice, in which the human 2E1
      was added back to mice deficient in the mouse 2E1. WT mice and the CYP2E1 KO and
      KI mice (both provided by Dr. F. Gonzalez, National Cancer Institute) were fed a
      high-fat Lieber-DeCarli ethanol liquid diet for 3weeks; pair-fed controls
      received dextrose. Ethanol produced fatty liver and oxidant stress in WT mice but
      liver injury (transaminases, histopathology) was minimal. Ethanol-induced
      steatosis and oxidant stress were blunted in the KO mice (no liver injury) but
      restored in the KI mice. Significant liver injury was produced in the ethanol-fed
      KI mice, with elevated transaminases, necrosis, and increased levels of collagen
      type 1 and smooth muscle actin. This liver injury in the KI mice was associated
      with elevated oxidant stress and elevated levels of the human CYP2E1 compared to
      levels of the mouse 2E1 in WT mice. Activation of JNK and decreased levels of Bcl
      2 and Bcl-XL were observed in the ethanol-fed KI mice compared to the other
      groups. Fatty liver in the WT and the KI mice was associated with lower levels of
      PPARalpha and acyl-CoA oxidase. No such changes were found in the ethanol-fed KO
      mice. These results show that CYP2E1 plays a major role in ethanol-induced fatty
      liver and oxidant stress. It is the absence of CYP2E1 in the KO mice that is
      responsible for the blunting of steatosis and oxidant stress because restoring
      the CYP2E1 restores the fatty liver and oxidant stress. Moreover, it is the human
      CYP2E1 that restores these effects of ethanol, which suggests that results for
      fatty liver and oxidant stress from rodent models of ethanol intake and mouse
      CYP2E1 can be extrapolated to human models of ethanol intake and to human CYP2E1.

PMID- 20692332
TI  - Proapoptotic effects of long-chain vitamin E metabolites in HepG2 cells are
      mediated by oxidative stress.
AB  - Although the metabolism of vitamin E has been extensively studied in cell
      culture, animals, and humans, biochemical analyses of intermediate metabolites
      are scarce. We here describe the synthesis and proapoptotic properties of long
      chain metabolites of alpha- and delta-tocopherol. Several long-chain vitamin E
      metabolites, namely 13'-hydroxy- and 13'-carboxychromanols, were synthesized from
      garcinoic acid, a delta-tocotrienol derivative extracted from the African bitter
      nut Garcinia kola. Both alpha- and delta-13'-carboxychromanol induced cell death
      in HepG2 cells at EC(50) of 13.5 and 6.5 MUM, respectively. Apoptosis was
      quantified by annexin V/7-AAD staining and flow cytometry analysis. By immunoblot
      analyses, we observed activation of both caspase-3 and caspase-9 as well as PARP
      1 cleavage. Parameters of mitochondrial dysfunction including reduced
      mitochondrial membrane potential and increased intracellular and
      intramitochondrial reactive oxygen species formation were observed after
      metabolite treatment. Last, long-chain hydroxychromanols were readily metabolized
      to the corresponding carboxychromanols in HepG2 cells. Taken together, these
      results indicate that long-chain metabolites may be responsible for
      antiproliferative properties of vitamin E vitamers.

PMID- 20692333
TI  - Thioredoxin-interacting protein inhibits hypoxia-inducible factor transcriptional
      activity.
AB  - Vascular endothelial growth factor (VEGF) is required for proper lung development
      and is transcriptionally regulated in alveolar epithelial cells by hypoxia
      inducible factor (HIF). Previous findings in a newborn mouse model of
      bronchopulmonary dysplasia (BPD) suggest that thioredoxin-interacting protein
      (Txnip) is a novel regulator of VEGF expression. The present studies were
      designed to test the hypothesis that Txnip negatively regulates VEGF through
      effects on HIF-mediated gene expression. To test this hypothesis, we first
      examined the levels of VEGF and Txnip protein in the lungs of 1-day-old newborn
      mice and E19 embryos and detected a significant inverse correlation. To elucidate
      the mechanisms underlying this relationship, we studied the effects of Txnip
      overexpression on HIF-mediated transcription using murine lung epithelial (MLE
      12) cells. Overexpression of Txnip inhibited HIF-mediated reporter activity in
      both hypoxia and room air. Suppression of HIF activity by Txnip seemed to be
      independent of the ability of Txnip to bind to thioredoxin. Thus, our studies
      support a model in which Txnip is a potentially critical regulator of HIF
      mediated gene transcription in the murine lung. Alterations in Txnip expression
      could alter lung VEGF expression in prematurely born human infants and contribute
      to the development of BPD.

PMID- 20692334
TI  - A radiation-induced adaptive response prolongs the survival of prion-infected
      mice.
AB  - Previously, it has been demonstrated that an "adaptive response" that includes
      the prevention, repair, and removal of oxidative damage can be evoked by
      radiation at dose rates substantially lower than those at which risks have been
      observed. The exact pathogenic mechanism of prion diseases is unknown, but
      circumstantial evidence suggests that oxidative stress plays a central role.
      Exposure of prion-infected mice to four 500 mGy/fraction doses of (60)Co gamma
      radiation administered every other day at a low dose rate (0.5 mGy/min) starting
      at 2 days before infection, 7 days postinfection (dpi), or 50 dpi significantly
      prolonged the survival of infected mice. The 500-mGy radiation treatments started
      at 50 dpi also significantly prolonged the symptom-free period of the disease and
      caused a significant delay in the rise of the 8-hydroxydeoxyguanosine
      concentration observed in the urine of nonirradiated infected mice at 98 dpi. The
      duration of the reduction in oxidative stress achieved by the radiation
      treatments was similar in length to the prolonged survival of the irradiated
      mice. This suggests that the adaptive response induced by low-dose whole-body
      radiation treatments prolongs the survival of prion-infected mice by reducing
      oxidative stress.

PMID- 20692335
TI  - Determinants of oxidant stress in extremely low birth weight premature infants.
AB  - Early in life, premature neonates are at risk of oxidant stress. They often
      require total parenteral nutrition (TPN), which is, however, contaminated with
      oxidation products. Coadministration of parenteral multivitamins (MVP) with a
      lipid emulsion (LIP) prevents lipid peroxidation. We hypothesized that LIP+MVP
      induces a lower oxidant load compared to preparations in which MVP is
      administered with an amino acid solution (AA+MVP). The aim of this study was to
      compare markers of oxidant stress in premature neonates receiving LIP+MVP, either
      exposed to or protected from light, or AA+MVP. Antioxidant vitamins, the redox
      potential of glutathione, isoprostane, and dityrosine were measured in urine or
      blood sampled on days 7 and 10 from babies requiring low (<0.25) vs high (>=0.25)
      fractional inspired O(2). Oxygen supplementation induced a more oxidized redox
      potential and increased dityrosine with AA+MVP only. Adding MVP in the lipid
      rather than the amino acid moiety of TPN protects against the oxidant stress
      associated with O(2) supplementation. Photoprotection added no benefit. Blood
      transfusions were found to produce a pronounced oxidant load masking the
      beneficial effect of LIP+MVP. The impact of these findings relates to a strong
      association between a more oxidized redox potential and later bronchopulmonary
      dysplasia, a clinical marker of oxidant stress.

PMID- 20692336
TI  - Knockout of the transcription factor NRF2 disrupts spermatogenesis in an age
      dependent manner.
AB  - Oxidative stress occurs when generation of reactive oxygen species (ROS)
      overwhelms antioxidant defenses. Oxidative stress has been associated with male
      infertility. The transcription factor nuclear factor-erythroid 2-related factor 2
      (NRF2) regulates basal and inducible transcription of genes encoding enzymes
      important for protection against ROS. We hypothesized that deletion of the Nrf2
      gene causes testicular and epididymal oxidative stress, which disrupts
      spermatogenesis. Our results show that male Nrf2(-/-) mice have decreased
      fertility compared to wild-type and heterozygous littermates, due to accumulating
      seminiferous tubule damage with increasing age. Testicular sperm head counts,
      epididymal sperm counts, and epididymal sperm motility in 2-month-old Nrf2(-/-)
      males did not differ from those of wild-type littermates; however, by age 6
      months, Nrf2(-/-) males had 44% lower testicular sperm head counts, 65% lower
      epididymal sperm counts, and 66% lower epididymal sperm motility than wild-type
      males. Two- to 4-month-old Nrf2(-/-) males had elevated levels of testicular and
      epididymal lipid peroxidation and testicular germ cell apoptosis, and decreased
      levels of antioxidants, compared to wild-type males. These results provide
      evidence that oxidative stress has deleterious effects on the testis and
      epididymis and demonstrate a critical role for the transcription factor NRF2 in
      preventing oxidative disruption of spermatogenesis.

PMID- 20692337
TI  - Effect of lysine modification on the stability and cellular binding of human
      amyloidogenic light chains.
AB  - AL amyloidosis is characterized by the pathologic deposition as fibrils of
      monoclonal light chains (i.e., Bence Jones proteins [BJPs]) in particular organs
      and tissues. This phenomenon has been attributed to the presence in amyloidogenic
      proteins of particular amino acids that cause these molecules to become unstable,
      as well as post-translational modifications and, in regard to the latter, we have
      investigated the effect of biotinylation of lysyl residues on cell binding. We
      utilized an experimental system designed to test if BJPs obtained from patients
      with AL amyloidosis or, as a control, multiple myeloma (MM), bound human
      fibroblasts and renal epithelial cells. As documented by fluorescence microscopy
      and ELISA, the amyloidogenic BJPs, as compared with MM components, bound
      preferentially and this reactivity increased significantly after chemical
      modification of their lysyl residues with sulfo-NHS-biotin. Further, based on
      tryptophan fluorescence and circular dichroism data, it was apparent that their
      conformation was altered, which we hypothesize exposed a binding site not
      accessible on the native protein. The results of our studies indicate that post
      translational structural modifications of pathologic light chains can enhance
      their capacity for cellular interaction and thus may contribute to the
      pathogenesis of AL amyloidosis and multiple myeloma.

PMID- 20692339
TI  - The mechanism underlying the appearance of late apoptotic neutrophils and
      subsequent TNF-alpha production at a late stage during Staphylococcus aureus
      bioparticle-induced peritoneal inflammation in inducible NO synthase-deficient
      mice.
AB  - During inflammation, neutrophils infiltrate into the involved site and undergo
      apoptosis. Early apoptotic neutrophils are then cleared by phagocytes, leading to
      resolution of the inflammation, whereas if late apoptotic neutrophils are
      accumulated for some reason, they provoke proinflammatory responses such as TNF
      alpha production. To determine how endogenously produced nitric oxide (NO)
      regulates neutrophil apoptosis and the resolution of inflammation, we compared
      peritoneal inflammation induced by Staphylococcus aureus bioparticles in wild
      type mice with that in inducible NO synthase (iNOS)-deficient ones. In this
      model, NO production was largely dependent on iNOS, the NO level peaking at 24 h.
      There were increases in the numbers of neutrophils and late apoptotic ones at 24
      h in iNOS-deficient mice as compared with in wild type ones, and consequently TNF
      alpha production at 36 h in iNOS-deficient mice. On the other hand, the
      administration of a NO donor to iNOS-deficient mice at 12 h decreased the numbers
      of neutrophils and late apoptotic ones at 24 h, and thereafter TNF-alpha
      production at 36 h. In addition, coculturing of macrophages with late apoptotic
      neutrophils caused TNF-alpha production and a NO donor inhibited the
      transmigration of neutrophils in a dose-dependent manner. Collectively, these
      results suggest a novel mechanism that endogenously produced NO suppresses
      neutrophil accumulation at a late stage of inflammation, thereby preventing the
      appearance of late apoptotic neutrophils and subsequent proinflammatory
      responses.

PMID- 20692338
TI  - The blood-brain barrier, chemokines and multiple sclerosis.
AB  - The infiltration of leukocytes into the central nervous system (CNS) is an
      essential step in the neuropathogenesis of multiple sclerosis (MS). Leukocyte
      extravasation from the bloodstream is a multistep process that depends on several
      factors including fluid dynamics within the vasculature and molecular
      interactions between circulating leukocytes and the vascular endothelium. An
      important step in this cascade is the presence of chemokines on the vascular
      endothelial cell surface. Chemokines displayed along the endothelial lumen bind
      chemokine receptors on circulating leukocytes, initiating intracellular signaling
      that culminates in integrin activation, leukocyte arrest, and extravasation. The
      presence of chemokines at the endothelial lumen can help guide the movement of
      leukocytes through peripheral tissues during normal immune surveillance, host
      defense or inflammation. The expression and display of homeostatic or
      inflammatory chemokines therefore critically determine which leukocyte subsets
      extravasate and enter the peripheral tissues. Within the CNS, however,
      infiltrating leukocytes that cross the endothelium face additional boundaries to
      parenchymal entry, including the abluminal presence of localizing cues that
      prevent egress from perivascular spaces. This review focuses on the differential
      display of chemokines along endothelial surfaces and how they impact leukocyte
      extravasation into parenchymal tissues, especially within the CNS. In particular,
      the display of chemokines by endothelial cells of the blood brain barrier may be
      altered during CNS autoimmune disease, promoting leukocyte entry into this
      immunologically distinct site. Recent advances in microscopic techniques,
      including two-photon and intravital imaging have provided new insights into the
      mechanisms of chemokine-mediated capture of leukocytes within the CNS.

PMID- 20692340
TI  - Targeted mutagenesis in the silkworm Bombyx mori using zinc finger nuclease mRNA
      injection.
AB  - Targeted mutagenesis is one of the key methods for functional gene analysis. A
      simplified variant of gene targeting uses direct microinjection of custom
      designed Zinc Finger Nuclease (ZFN) mRNAs into Drosophila embryos. To evaluate
      the applicability of this method to gene targeting in another insect, we
      mutagenized the Bombyx mori epidermal color marker gene BmBLOS2, which controls
      the formation of uric acid granules in the larval epidermis. Our results revealed
      that ZFN mRNA injection is effective to induce somatic, as well as germline,
      mutations in a targeted gene by non-homologous end joining (NHEJ). The ZFN
      induced NHEJ mutations lack end-filling and blunt ligation products, and include
      mainly 7 bp or longer deletions, as well as single nucleotide insertions. These
      observations suggest that the B. mori double-strand break repair system relies on
      microhomologies rather than on a canonical ligase IV-dependent mechanism. The
      frequency of germline mutants in G(1) was sufficient to be used for gene
      targeting relying on a screen based solely on molecular methods.

PMID- 20692341
TI  - Differential expression of proteins in the midgut of Anopheles albimanus infected
      with Plasmodium berghei.
AB  - The main vector for transmission of malaria in Mexico is the Anopheles albimanus
      mosquito. The midgut of disease-transmitting mosquitoes carries out a variety of
      functions that are related to blood feeding. We analyzed the midgut of A.
      albimanus infected with Plasmodium berghei (resistant mosquito) using a proteomic
      approach to identify putative short peptides that are enriched in the midgut
      after blood feeding. Mosquito midguts were analyzed by two-dimensional
      electrophoresis to determine the changes in protein profiles. We identified 21
      spot proteins that are differentially expressed in the blood of mosquitoes during
      the immune challenge. Molecular weight of the spots varied from 13 to 36 kDa,
      with a broad isoelectric point range of 3.92-8.90. We identified the
      differentially expressed proteins using mass spectrometry and constructed a
      proteomic data base of the A. albimanus midgut with diverse functions, some of
      them proteins with digestive and immunologic functions. Identification of these
      proteins may have important implications for understanding the blood meal
      digestion process, as well as developing novel vector control strategies and
      understanding parasite vector interactions.

PMID- 20692342
TI  - Reversal of age-related thymic involution by an LHRH agonist in miniature swine.
AB  - BACKGROUND AND AIMS OF STUDY: We have previously demonstrated a requirement for
      the presence of a juvenile thymus for the induction of transplantation tolerance
      to renal allografts by a short-course of calcineurin inhibition in miniature
      swine. We have also shown that aged, involuted thymi can be rejuvenated when
      transplanted as vascularized thymic lobes into juvenile swine recipients. The
      present studies were aimed at elucidating the extrinsic factors facilitating this
      restoration of function in the aged thymus. In particular, we tested the impact
      of sex steroid blockade by Luteinizing Hormone-Releasing Hormone (LHRH).
      MATERIALS AND METHODS: 30 naive animals (25 males and 5 females) were used for
      measurement of serum testosterone levels. 3 mature male pigs (aged at 22, 22 and
      29 months old) were used to test the effects of Lupron (LHRH analog) injection at
      45 mg (per 70-80 kg body weight) as a 3-month depot on testosterone levels and
      thymic rejuvenation. Thymic rejuvenation was assessed by histology, flow
      cytometric analysis, morphometric analysis and TREC assays. RESULTS: Hormonal
      alterations were induced by Lupron and resulted in macroscopic and histologic
      regeneration of the thymus of aged animals within 2 months, as evidenced by
      restoration of juvenile thymus architecture and increased cellularity. Two
      animals that were evaluated for TREC both showed increased levels in the
      periphery following Lupron treatment. CONCLUSION: Treatment of aged animals with
      Lupron leads to thymic rejuventaion in adult miniature swine. This result could
      expand the applicability of thymus-dependent tolerance-inducing regimens to adult
      recipients.

PMID- 20692343
TI  - Carvedilol treatment reduces transthyretin deposition in a familial amyloidotic
      polyneuropathy mouse model.
AB  - Carvedilol is a beta-antagonist with strong anti-oxidant effect in lipids,
      proteins and superoxide production protecting biological membranes from oxidative
      stress. We hypothesised a possible therapeutical application of carvedilol in
      familial amyloidotic polyneuropathy (FAP), a neurodegenerative disease caused by
      deposition of transthyretin (TTR) amyloid fibrils. Oxidative stress, apoptosis
      and inflammation related to aggregation of non-fibrillar and fibrillar TTR have
      been detected both in pre-symptomatic and symptomatic stages of the disease,
      respectively. In this study we show by semi-quantitative immunohistochemistry and
      western blot analysis that administration of carvedilol to a transgenic mouse
      model of FAP influences the expression of oxidative and apoptotic biomarkers
      usually associated with TTR deposition, namely oxidation products such as HNE and
      8-OHdG, and markers of ER stress. Most important, carvedilol treatment
      significantly reduced TTR aggregates in as much as 50%. We also observed that
      carvedilol rescues a mice neuroblastoma cell line from death induced by TTR
      oligomers, by decreasing activation of BiP and other ER stress biomarkers. Since
      carvedilol has no effect on TTR aggregation "in vitro", this finding points for
      the "in vivo" modulation of TTR aggregation by oxidative stress and apoptosis and
      prompts for the use of this safe drug in prophylactic and therapeutical measures
      in the FAP population.

PMID- 20692344
TI  - Uncx regulates proliferation of neural progenitor cells and neuronal survival in
      the olfactory epithelium.
AB  - Uncx (Phd1, Chx4) is a paired homeobox transcription factor gene. It and its
      probable functional partners, Tle co-repressors, were expressed by neurally-fated
      basal progenitor cells and olfactory sensory neurons of the olfactory epithelium.
      Uncx expression was rare in olfactory epithelia of Ascl1(-/-) mice, but common in
      Neurog1(-/-) mice. In Uncx(-/-) mice olfactory progenitor cell proliferation,
      progenitor cell number, olfactory sensory neuron survival, and Umodl1 and Kcnc4
      mRNAs were reduced. Evidence of sensory neuron activity and functional
      connections to the olfactory bulb argue that decreased neuronal survival was not
      due to loss of trophic support or activity-dependent mechanisms. These data
      suggest that UNCX acts downstream of neural determination factors to broadly
      control transcriptional mechanisms used by neural progenitor cells to specify
      neural phenotypes.

PMID- 20692345
TI  - Adenylate Cyclase 1 modulates peripheral nerve branching patterns.
AB  - The Ca(2+)-stimulated adenylate cyclase 1 (AC1) is a key mediator of retinotopic
      map refinement and is required for the retraction response of retinal growth
      cones to the guidance cue ephrin-A5. We show here that AC1 is dynamically
      expressed in subpopulations of motor neurons in the spinal cord and sensory
      neurons of the dorsal root ganglia during development. AC1 was first detected
      around E12.5 in motoneurons of the medial aspect of the lateral motor column
      (LMCm) and the lateral region of the medial motor column (MMCl), which project to
      the ventral limb and body wall musculature, respectively. Expression levels
      gradually increased until they reached a maximum at a time when peripheral
      sensory and motor axons branch and establish connections with their targets. In
      barrelless mice, where a mutation inactivates the AC1 gene, sensory projections
      to the skin in the limbs and trunk region as well as innervations of the
      intercostal musculature provided by MMCl axons show increased branching. These
      results suggest a function of AC1 in the formation of peripheral nerve
      trajectories such as branching and pruning, after the initial projections have
      been laid down.

PMID- 20692346
TI  - Production of protein complexes via co-expression.
AB  - Multi-protein complexes are involved in essentially all cellular processes. A
      protein's function is defined by a combination of its own properties, its
      interacting partners, and the stoichiometry of each. Depending on binding
      partners, a transcription factor can function as an activator in one instance and
      a repressor in another. The study of protein function or malfunction is best
      performed in the relevant context. While many protein complexes can be
      reconstituted from individual component proteins after being produced
      individually, many others require co-expression of their native partners in the
      host cells for proper folding, stability, and activity. Protein co-expression has
      led to the production of a variety of biological active complexes in sufficient
      quantities for biochemical, biophysical, structural studies, and high throughput
      screens. This article summarizes examples of such cases and discusses critical
      considerations in selecting co-expression partners, and strategies to achieve
      successful production of protein complexes.

PMID- 20692347
TI  - Immunosuppressive effects of environmental stressors on immunological function in
      Pinctada imbricata.
AB  - This study assessed the effects of mechanical agitation, hypo-saline conditions,
      and exposure to the air on the Akoya pearl oyster, Pinctada imbricata, focusing
      specifically on the immunological activity of haemocytes. Both phagocytosis and
      phenoloxidase activity decreased significantly when oysters were exposed to all
      three stressors. Transient decreases were also evident in total haemocyte counts
      after mechanical stress and exposure to air, while significant increases in total
      haemocyte counts were evident after exposure to low salinity. Acid phosphatase
      activity increased significantly when oysters were exposed to air. The frequency
      of granulocytes in the haemolymph increased significantly when oysters were
      stressed by hypo-saline conditions, whilst the relative frequency of granulocytes
      did not differ significantly after mechanical agitation or exposure to air. The
      total protein content of haemolymph increased significantly when oysters were
      stressed by mechanical agitation and low salinity. These results suggest that
      fluctuations in environmental conditions affect circulating haemocytes and their
      cytochemistry, and that the different immunological parameters tested were
      influenced uniquely according to the type of stressor.

PMID- 20692348
TI  - Molecular cloning and characterization of bloodthirsty from Atlantic cod (Gadus
      morhua).
AB  - The tripartite motif (TRIM) proteins are involved in a variety of cellular
      functions including cell proliferation, differentiation, development,
      oncogenesis, apoptosis and antiviral activity. In this study, we report the
      identification and characterization of an Atlantic cod tripartite motif
      containing protein named bloodthirsty from a poly I:C subtractive cDNA library.
      The Atlantic cod bloodthirsty (Acbloodthirsty) has a predicted open reading frame
      of 541 amino acids, encoding a putative 64-kDa protein. The N-terminal region
      contains the three motifs typical of TRIM proteins, a RING finger, one B-box, and
      a coiled-coil domain, which together form the TRIM motif found in this large
      family of proteins, whereas the C-terminal region contains a PRYSPRY domain. The
      intracellular localization of Acbloodthirsty in CHSE-214 cells showed mostly
      diffuse staining with some discrete compartments in the cytoplasm. The induction
      of bloodthirsty transcripts by poly I:C was seen in spleen using quantitative
      reverse transcriptase PCR (RT-qPCR). The expression pattern indicates that
      Acbloodthirsty is involved in antiviral immune response in Atlantic cod.

PMID- 20692349
TI  - Did you get the beat? Late proficient French-German learners extract strong-weak
      patterns in tonal but not in linguistic sequences.
AB  - Event-related potential (ERP) data in French and German have shown that metric
      violations (i.e. incorrectly stressed words) in a sentence elicit a P600.
      Furthermore, French speakers find it difficult to discriminate stimuli that vary
      in word stress position and have been labelled as "stress deaf." In the current
      study we investigated (i) whether French late learners of German can perceive
      deviations of a regular strong-weak stress pattern (trochee) in German sentences,
      and (ii) whether the same subjects differ in their electrophysiological response
      from German monolinguals in a non-linguistic "subjective rhythmization" paradigm.
      Irrespective of the native language both groups show similar results in the
      latter paradigm in which isochronous stimulus trains are subjectively converted
      into a binary strong-weak grouped percept (trochee). However, we report
      differences between native and non-native speakers of German in the sentence
      paradigm. In contrast to German native speakers French late learners of German
      fail to show a P600 component in response to deviations from a regular trochaic
      stress pattern, although attention was directed to the metric pattern of the
      sentences. The current data suggest that French stress deafness selectively
      affects the perception of a strong-weak pattern in sentences while strong-weak
      grouping of non-linguistic sequences is not language specific. The results imply
      that linguistic and non-linguistic grouping do not rely on the same neural
      mechanisms.

PMID- 20692350
TI  - Perception of object motion in three-dimensional space induced by cast shadows.
AB  - Cast shadows can be salient depth cues in three-dimensional (3D) vision. Using a
      motion illusion in which a ball is perceived to roll in depth on the bottom or to
      flow in the front plane depending on the slope of the trajectory of its cast
      shadow, we investigated cortical mechanisms underlying 3D vision based on cast
      shadows using fMRI techniques. When modified versions of the original illusion,
      in which the slope of the shadow trajectory (shadow slope) was changed in 5 steps
      from the same one as the ball trajectory to the horizontal, were presented to
      participants, their perceived ball trajectory shifted gradually from rolling on
      the bottom to floating in the front plane as the change of the shadow slope. This
      observation suggests that the perception of the ball trajectory in this illusion
      is strongly affected by the motion of the cast shadow. In the fMRI study,
      cortical activity during observation of the movies of the illusion was
      investigated. We found that the bilateral posterior-occipital sulcus (POS) and
      right ventral precuneus showed activation related to the perception of the ball
      trajectory induced by the cast shadows in the illusion. Of these areas, it was
      suggested that the right POS may be involved in the inferring of the ball
      trajectory by the given spatial relation between the ball and the shadow. Our
      present results suggest that the posterior portion of the medial parietal cortex
      may be involved in 3D vision by cast shadows.

PMID- 20692351
TI  - Real-time support vector classification and feedback of multiple emotional brain
      states.
AB  - An important question that confronts current research in affective neuroscience
      as well as in the treatment of emotional disorders is whether it is possible to
      determine the emotional state of a person based on the measurement of brain
      activity alone. Here, we first show that an online support vector machine (SVM)
      can be built to recognize two discrete emotional states, such as happiness and
      disgust from fMRI signals, in healthy individuals instructed to recall
      emotionally salient episodes from their lives. We report the first application of
      real-time head motion correction, spatial smoothing and feature selection based
      on a new method called Effect mapping. The classifier also showed robust
      prediction rates in decoding three discrete emotional states (happiness, disgust
      and sadness) in an extended group of participants. Subjective reports ascertained
      that participants performed emotion imagery and that the online classifier
      decoded emotions and not arbitrary states of the brain. Offline whole brain
      classification as well as region-of-interest classification in 24 brain areas
      previously implicated in emotion processing revealed that the frontal cortex was
      critically involved in emotion induction by imagery. We also demonstrate an fMRI
      BCI based on real-time classification of BOLD signals from multiple brain
      regions, for each repetition time (TR) of scanning, providing visual feedback of
      emotional states to the participant for potential applications in the clinical
      treatment of dysfunctional affect.

PMID- 20692352
TI  - Cultural studies coupled with DNA based sequence analyses and its implication on
      pigmentation as a phylogenetic marker in Pestalotiopsis taxonomy.
AB  - Previous phylogenetic studies based on DNA sequence data have partially resolved
      taxonomic relationships among Pestalotiopsis species. There are still some
      morphological characters whose phylogenetic significance have not been assessed
      properly due to limited taxon sampling, in particular the degree of pigmentation
      of median cells. In this study, the stability of pigmentation of median cells of
      conidia in Pestalotiopsis species was evaluated in subculture, and a molecular
      phylogenetic analysis was conducted on 45 strains belonging to 26 species in
      order to reappraise the pigmentation of median cells for its significance in the
      taxonomy of Pestalotiopsis. Phylogenetic relationships were inferred from
      nucleotide sequences in ITS regions (ITS1, 5.8S and ITS2) and beta-tubulin 2 gene
      (tub2). The results showed that pigmentation of median cells was stable and it
      could be a key character in the taxonomy of Pestalotiopsis species. Instead of
      "concolorous" and "versicolor" proposed by Steyeart (1949), "brown to olivaceous"
      and "umber to fuliginous" are described and proposed in this paper.

PMID- 20692353
TI  - The RETHINK project: impact of toxicity testing in the minipig as an alternative
      approach in regulatory toxicity testing.

PMID- 20692354
TI  - Adult bone marrow stromal cell-based tissue-engineered aggrecan exhibits
      ultrastructure and nanomechanical properties superior to native cartilage.
AB  - OBJECTIVE: To quantify the structural characteristics and nanomechanical
      properties of aggrecan produced by adult bone marrow stromal cells (BMSCs) in
      peptide hydrogel scaffolds and compare to aggrecan from adult articular
      cartilage. DESIGN: Adult equine BMSCs were encapsulated in 3D-peptide hydrogels
      and cultured for 21 days with TGF-beta1 to induce chondrogenic differentiation.
      BMSC-aggrecan was extracted and compared with aggrecan from age-matched adult
      equine articular cartilage. Single molecules of aggrecan were visualized by
      atomic force microscopy-based imaging and aggrecan nanomechanical stiffness was
      quantified by high resolution force microscopy. Population-averaged measures of
      aggrecan hydrodynamic size, core protein structures and CS sulfation compositions
      were determined by size-exclusion chromatography, Western analysis, and
      fluorescence-assisted carbohydrate electrophoresis (FACE). RESULTS: BMSC-aggrecan
      was primarily full-length while cartilage-aggrecan had many fragments. Single
      molecule measurements showed that core protein and GAG chains of BMSC-aggrecan
      were markedly longer than those of cartilage-aggrecan. Comparing full-length
      aggrecan of both species, BMSC-aggrecan had longer GAG chains, while the core
      protein trace lengths were similar. FACE analysis detected a ~ 1:1 ratio of
      chondroitin-4-sulfate to chondroitin-6-sulfate in BMSC-GAG, a phenotype
      consistent with aggrecan from skeletally-immature cartilage. The nanomechanical
      stiffness of BMSC-aggrecan was demonstrably greater than that of cartilage
      aggrecan at the same total sGAG (fixed charge) density. CONCLUSIONS: The higher
      proportion of full-length monomers, longer GAG chains and greater stiffness of
      the BMSC-aggrecan makes it biomechanically superior to adult cartilage-aggrecan.
      Aggrecan stiffness was not solely dependent on fixed charge density, but also on
      GAG molecular ultrastructure. These results support the use of adult BMSCs for
      cell-based cartilage repair.

PMID- 20692355
TI  - Cathepsin K inhibition reduces CTXII levels and joint pain in the guinea pig
      model of spontaneous osteoarthritis.
AB  - Cathepsin K is a cysteine proteinase which is believed to contribute to
      osteoarthritis (OA) pathogenesis. This brief report evaluates the effect of the
      novel selective cathepsin K inhibitor AZ12606133 on cartilage metabolism in the
      Dunkin-Hartley guinea pig model of spontaneous OA. In parallel,
      electrophysiological studies were performed to determine whether acute and
      chronic treatment with the cathepsin K inhibitor could alter joint nociception.
      Acute treatment of OA knees with AZ12606133 had no effect on joint afferent nerve
      activity; however, prolonged (1 month) administration of the cathepsin K
      inhibitor delivered via a chronically implanted osmotic pump significantly
      reduced mechanosensitivity in response to both non-noxious and noxious joint
      movements. Urinal concentrations of the cartilage breakdown products cross-linked
      C-telopeptides of type II collagen (CTXII) were also reduced by chronic cathepsin
      K inhibition. These data suggest that prolonged AZ12606133 administration can
      reduce cartilage turnover and joint nociception in the Dunkin-Hartley guinea pig
      model of spontaneous OA.

PMID- 20692356
TI  - Trial-unique, delayed nonmatching-to-location (TUNL): a novel, highly hippocampus
      dependent automated touchscreen test of location memory and pattern separation.
AB  - The hippocampus is known to be important for learning and memory, and is
      implicated in many neurodegenerative diseases. Accordingly many animal models of
      learning and memory focus on hippocampus-dependent tests of location learning and
      memory. These tests often use dry mazes or water mazes; however automated testing
      in operant chambers confers many advantages over such methods. Some automated
      tests of location memory, such as delayed nonmatching-to-position (DNMTP) have,
      however, fallen out of favor following the discovery that such tasks can be
      solved using mediating behaviors that can bridge the delay and reduce the
      requirement for memory per se. Furthermore some researchers report that DNMTP
      performance may not always require the hippocampus. Thus, in an attempt to
      develop a highly hippocampus-dependent automated test of location memory that
      elicits fewer mediating behaviors, we have developed a trial-unique nonmatching
      to-location (TUNL) task, carried out in a computer-automated touchscreen testing
      apparatus. To test the efficacy of this assay, rats with lesions to the
      hippocampus, or a sham lesion control group, were tested under a variety of
      conditions. Both groups were able to perform well at a delay of 1s, but the
      lesion group was highly impaired when tested at a 6s delay. Moreover, animals
      with lesions of the hippocampus showed a greater impairment when the distance
      between the locations was reduced. This result indicates that TUNL can be used to
      investigate both memory across a delay, and spatial pattern separation (the
      ability to disambiguate similar spatial locations). Performance-enhancing
      mediating behaviors during the task were found to be minimal. Thus, the TUNL task
      has the potential to serve as a powerful tool for the study of the neurobiology
      of learning and memory.

PMID- 20692357
TI  - Activation of heat shock factor 1 plays a role in pyrrolidine dithiocarbamate
      mediated expression of the co-chaperone BAG3.
AB  - Adaptive responses to physical and inflammatory stressors are mediated by
      transcription factors and molecular chaperones. The transcription factor heat
      shock factor 1 (HSF1) has been implicated in extending lifespan in part by
      increasing expression of heat shock response genes. Pyrrolidine dithiocarbamate
      (PDTC) is a small thiol compound that exerts in vivo and in vitro anti
      inflammatory properties through mechanisms that remain unclear. Here we report
      that PDTC induced the release of monomeric HSF1 from the molecular chaperone heat
      shock protein 90 (Hsp90), with concomitant increase in HSF1 trimer formation,
      translocation to the nucleus, and binding to promoter of target genes in human
      HepG2 cells. siRNA-mediated silencing of HSF1 blocked BAG3 gene expression by
      PDTC. The protein levels of the co-chaperone BAG3 and its interaction partner
      Hsp72 were stimulated by PDTC in a dose-dependent fashion, peaking at 6h.
      Inhibition of Hsp90 function by geldanamycin derivatives and novobiocin elicited
      a pattern of HSF1 activation and BAG3 expression that was similar to PDTC.
      Chromatin immunoprecipitation studies showed that PDTC and the inhibitor 17
      dimethylaminoethylamino-17-demethoxygeldanamycin enhanced the binding of HSF1 to
      the promoter of several target genes, including BAG3, HSPA1A, HSPA1B, FKBP4,
      STIP1 and UBB. Cell treatment with PDTC increased significantly the level of
      Hsp90alpha thiol oxidation, a posttranslational modification known to inhibit its
      chaperone function. These results unravel a previously unrecognized mechanism by
      which PDTC and related compounds could confer cellular protection against
      inflammation through HSF1-induced expression of heat shock response genes.

PMID- 20692358
TI  - HDAC inhibitor-induced activation of NF-kappaB prevents apoptotic response of
      E1A+Ras-transformed cells to proapoptotic stimuli.
AB  - HDAC inhibitors (HDACIs) are capable of suppressing the cell growth of tumour
      cells due to the induction of apoptosis and/or cell cycle arrest. This allows of
      considering HDACIs as promising agents for tumour therapy. The final outcome -
      apoptotic cell death or cell cycle arrest - depends on the type of tumour and
      cellular context. In this report, we addressed the issue by analysing effects
      produced in E1A+Ras-transformed MEF cells by HDAC inhibitors sodium butyrate
      (NaB), Trichostatin A (TSA) and some others. It has been shown that the HDACIs
      induced cell cycle arrest in E1A+Ras-transformed cells but not apoptosis. The
      antiapoptotic effect of HDACIs is likely to be a result of NF-kappaB-dependent
      signaling pathway activation. HDACI-induced activation of NF-kappaB takes place
      in spite of a deregulated PI3K/Akt pathway in E1A+Ras cells, suggesting an
      alternative mechanism for the activation of NF-kappaB based on acetylation. HDACI
      dependent activation of NF-kappaB prevents the induction of apoptosis by
      cytostatic agent adriamycin and serum deprivation. Accordingly, suppression of NF
      kappaB activity in HDACI-arrested cells by the chemical inhibitor CAPE or RelA
      siRNA resulted in the induction of an apoptotic programme. Thus, our findings
      suggest that the activation of the NF-kappaB pathway in HDACI-treated E1A+Ras
      transformed cells blocks apoptosis and may thereby play a role in triggering the
      programme of cell cycle arrest and cellular senescence.

PMID- 20692359
TI  - Resveratrol and derivatives for the prevention and treatment of cancer.
AB  - Resveratrol, a naturally derived stilbene that exists in various foods and
      beverages, has attracted increasing attention over the past decade because of its
      multiple beneficial properties, including chemopreventive and antitumor
      activities. There are several other natural derivatives of resveratrol that are
      structurally similar to resveratrol and are also present in food. In addition, a
      series of resveratrol analogs have been synthesized by the addition of defined
      functional groups to increase the potency and/or enhance the activity of specific
      properties of resveratrol. Such resveratrol derivatives might provide promising
      tools as cancer chemopreventive agents, as well as cancer therapeutics in the
      prevention and treatment of cancer. This review provides an overview of key
      derivatives of resveratrol as cancer therapeutics.

PMID- 20692360
TI  - Cancer therapy via modulation of micro RNA levels: a promising future.
AB  - Micro RNAs (miRNAs) are a class of naturally occurring ~ 22 nt long non-coding
      small RNA molecules that regulate the expression of a wide range of genes
      involved in development, growth, proliferation and apoptosis. miRNAs are
      evolutionarily conserved from plants to animals, and they regulate and fine-tune
      a diverse array of biological processes. Recently, they have been shown to act as
      either oncogenes or tumor suppressors in a wide variety of tumors. Here, we
      review the studies that document the role of miRNAs as key players in human
      cancer and the potential therapeutic modality of exploiting miRNAs for cancer
      prognosis and treatment.

PMID- 20692361
TI  - Assessment of DNA damage induced by extracts, fractions and isolated compounds of
      Davilla nitida and Davilla elliptica (Dilleniaceae).
AB  - Davilla nitida and Davilla elliptica (Dilleniaceae) are plants that occur
      predominantly in the cerrado region of South America. They are used in popular
      medicine to treat stomach diseases, diarrhea and swelling, particularly of the
      lymph nodes and testicles. Chemical investigation of these two plant species led
      to the identification of the compounds myricetin-3-O-alpha-l-rhamnoside
      (myricitrin), quercetin-3-O-alpha-l-rhamnoside (quercitrin), myricetin, quercetin
      and gallic acid derivatives in the leaves of D. nitida and D. elliptica.
      Therefore, it was concluded that the two species of Davilla possess qualitatively
      similar chemical profiles. In the present study, the mutagenic and genotoxic
      potential of these plants and of their isolated compounds was tested in the
      Salmonella typhimurium assay (Ames test) with strains TA100, TA98, TA102 and
      TA97a, in the micronucleus test with peripheral blood cells of mice treated in
      vivo, and in plasmid DNA to analyze DNA strand-breaks. In the assessment of
      mutagenic potential by the Ames test, extracts from both plant species and a D.
      nitida ethyl-acetate fraction induced positive responses. On the other hand, none
      of the extracts showed genotoxic activity in the mouse cells. In the presence of
      metal ion, D. nitida and D. elliptica aqueous and ethyl-acetate fractions, as
      well as their isolated compounds, induced single- and double-strand-breaks in
      plasmid DNA in a cell-free system.

PMID- 20692362
TI  - Comparison of different methods for an accurate assessment of cytotoxicity in the
      in vitro micronucleus test without cytokinesis block.
AB  - A European collaborative study was conducted in order to investigate the
      different measurements of cytotoxicity assessment in the in vitro micronucleus
      test. Relative population doubling and relative increase in cell counts were the
      measurements of cytotoxicity assessed in this study. The test chemicals,
      etoposide, benzo[a]pyrene, cytosine arabinoside and diethylstilboestrol were
      tested in this in vitro micronucleus assay, in mouse lymphoma L5178Y cells,
      without cytokinesis block. This study was conducted in support of the toxicity
      measurements recommended in the draft OECD Test Guideline 487. Etoposide,
      benzo[a]pyrene and cytosine arabinoside produced positive responses at
      concentrations where approximately 50% toxicity was observed measured by relative
      population doubling and relative increase in cell counts. Diethylstilboestrol was
      negative at all concentrations tested. These results are in concordance with the
      principles of the draft OECD Test Guideline 487.

PMID- 20692363
TI  - Lipin - The bridge between hepatic glycerolipid biosynthesis and lipoprotein
      metabolism.
AB  - Growing evidence links the three mammalian lipin proteins, i.e., lipin-1, lipin-2
      and lipin-3, to metabolic and cardiovascular diseases such as noninsulin
      dependent diabetes mellitus and atherosclerosis. Lipin proteins play a dual
      function in lipid metabolism by acting as phosphatidate phosphatase (PAP) enzymes
      and as transcriptional regulators. Genetic variants within the human LPIN1 and
      LPIN2 genes are associated with metabolic syndromes. The fatty liver dystrophy
      (fld) mice carrying mutations within the Lpin1 gene display life-long deficiency
      in adipogenesis, insulin resistance, neonatal hepatosteatosis and
      hypertriglyceridemia, as well as increased atherosclerosis susceptibility. Cell
      culture studies show that hepatic lipin-1 expression is selectively stimulated by
      glucocorticoids and repressed by insulin, and its subcellular localization
      governs the assembly and secretion of very low density lipoproteins (VLDL). In
      noninsulin-dependent diabetes, glucocorticoid signals lead to dyslipidemia
      characterized by overproduction of VLDL and atherogenic remnants. This puts lipin
      1 as a key integrator of hormonal signals to the liver in diabetic dyslipidemia.
      This review summarizes the current understanding of the role that hepatic lipin-1
      plays in the synthesis, storage and compartmentalization of glycerolipids, and
      highlights the lipid metabolic consequences associated with dysregulated lipin
      expression.

PMID- 20692364
TI  - Swimming impairment and acetylcholinesterase inhibition in zebrafish exposed to
      copper or chlorpyrifos separately, or as mixtures.
AB  - Pesticides such as chlorpyrifos (CPF) and metals such as copper can impair
      swimming behavior in fish. However, the impact to swimming behavior from exposure
      to mixtures of neurotoxicants has received little attention. In the current
      study, we analyzed spontaneous swimming rates of adult zebrafish (Danio rerio) to
      investigate in vivo mixture interactions involving two chemical classes.
      Zebrafish were exposed to the neurotoxicants copper chloride (CuCl, 0.1 MUM, 0.25
      MUM, 0.6 MUM, or 6.3, 16, 40 ppb), chlorpyrifos (CPF, 0.1 MUM, 0.25 MUM, 0.6 MUM,
      or 35, 88, 220 ppb) and binary mixtures for 24h to better understand the effects
      of Cu on CPF neurotoxicity. Exposure to CPF increased the number of animals
      undergoing freeze responses (an anti-predator behavior) and, at the highest CPF
      dose (0.6 MUM), elicited a decrease in zebrafish swimming rates. Interestingly,
      the addition of Cu caused a reduction in the number of zebrafish in the CPF
      exposure groups undergoing freeze responses. There was no evidence of additive or
      synergistic toxicity between Cu and CPF. Although muscle AChE activity was
      significantly reduced by CPF, there was a relatively poor relationship among
      muscle AChE concentrations and swimming behavior, suggesting non-muscle AChE
      mechanisms in the loss of swimming behavior. In summary, we have observed a
      modulating effect of Cu on CPF swimming impairment that appears to involve both
      AChE and non-AChE mechanisms. Our study supports the utility of zebrafish in
      understanding chemical mixture interactions and neurobehavioral injury.

PMID- 20692365
TI  - Bioinsecticidal activity of Talisia esculenta reserve protein on growth and
      serine digestive enzymes during larval development of Anticarsia gemmatalis.
AB  - Plants synthesize a variety of molecules to defend themselves against an attack
      by insects. Talisin is a reserve protein from Talisia esculenta seeds, the first
      to be characterized from the family Sapindaceae. In this study, the insecticidal
      activity of Talisin was tested by incorporating the reserve protein into an
      artificial diet fed to the velvetbean caterpillar Anticarsia gemmatalis, the
      major pest of soybean crops in Brazil. At 1.5% (w/w) of the dietary protein,
      Talisin affected larval growth, pupal weight, development and mortality, adult
      fertility and longevity, and produced malformations in pupae and adult insects.
      Talisin inhibited the trypsin-like activity of larval midgut homogenates. The
      trypsin activity in Talisin-fed larvae was sensitive to Talisin, indicating that
      no novel protease-resistant to Talisin was induced in Talisin-fed larvae.
      Affinity chromatography showed that Talisin bound to midgut proteinases of the
      insect A. gemmatalis, but was resistant to enzymatic digestion by these larval
      proteinases. The transformation of genes coding for this reserve protein could be
      useful for developing insect resistant crops.

PMID- 20692366
TI  - Source authenticity in the UMLS--a case study of the Minimal Standard
      Terminology.
AB  - As the UMLS integrates multiple source vocabularies, the integration process
      requires that certain adaptation be applied to the source. Our interest is in
      examining the relationship between the UMLS representation of a source vocabulary
      and the source vocabulary itself. We investigated the integration of the Minimal
      Standard Terminology (MST) into the UMLS in order to examine how close its UMLS
      representation is to the source MST. The MST was conceived as a "minimal" list of
      terms and structure intended for use within computer systems to facilitate
      standardized reporting of gastrointestinal endoscopic examinations. Although the
      MST has an overall schema and implied relationship structure, many of the UMLS
      integrated MST terms were found to be hierarchically orphaned, and with lateral
      relationships that do not closely adhere to the source MST. Thus, the MST
      representation within the UMLS significantly differs from that of the source MST.
      These representation discrepancies may affect the usability of the MST
      representation in the UMLS for knowledge acquisition. Furthermore, they pose a
      problem from the perspective of application developers. While these findings may
      not necessarily apply to other source terminologies, they highlight the conflict
      between preservation of authentic concept orientation and the UMLS overall desire
      to provide fully specified names for all source terms.

PMID- 20692367
TI  - Granulocytic sarcoma of the colon.

PMID- 20692368
TI  - Intentional swallowing of foreign bodies is a recurrent and costly problem that
      rarely causes endoscopy complications.
AB  - BACKGROUND & AIMS: Guidelines support endoscopic removal of certain gastric
      foreign bodies (FBs) and all FBs lodged in the esophagus. We studied the poorly
      understood group of patients who intentionally ingest FBs. METHODS: Cases of
      intentional ingestion of FBs (n = 305) were identified, retrospectively, from an
      electronic endoscopy database and followed. Cases occurred among 33 different
      patients, who underwent endoscopy from October 1, 2001, to July 31, 2009 (39.0
      cases/year); 79% were diagnosed with a psychiatric disorder. Financial cost
      analysis was performed using hospital billing and cost systems. RESULTS: Commonly
      ingested FBs included pens (23.6%), batteries (9.2%), knives (7.2%), and razor
      blades (6.9%). Most endoscopic procedures were performed under general
      anesthesia. FBs were commonly retrieved by snares (58.0%), rat-toothed forceps
      (14.4%), and nets (11.5%), assisted sometimes by use of overtubes (10.8%), and
      hoods (4.6%). FB extraction was unsuccessful at the initial endoscopy in only 20
      cases; 2 cases eventually required surgical extraction. Minor complications
      occurred in 11 endoscopies. There were no deaths or perforations. The total
      estimated costs were $2,018,073 ($1,500,627 in hospital costs, $240,640 in
      physician fees, and $276,806 for security services). Costs were significantly
      higher for inpatients. Major payers were Medicare (48%) and Medicaid (31%).
      CONCLUSIONS: Intentional FB ingestion occurs among a relatively small number of
      patients with psychiatric disorders and is costly. Endoscopic retrieval is
      relatively effective and safe, but often requires general anesthesia. These cases
      utilize significant hospital and fiscal resources. Attention should be focused on
      preventing these recurrent and costly episodes.

PMID- 20692369
TI  - Undisclosed use of nonsteroidal anti-inflammatory drugs may underlie small-bowel
      injury observed by capsule endoscopy.
AB  - BACKGROUND & AIMS: Findings from capsule endoscopies (CEs) of patients with
      enteropathy from nonsteroidal anti-inflammatory drugs (NSAIDs) may be
      indistinguishable from those with Crohn's disease, making medication history
      crucial to image interpretation. Undeclared NSAID use has been proposed to cause
      unexplained peptic ulcers; we investigated whether it is also an issue among
      patients referred for small-bowel CE. METHODS: We collected demographic data,
      indications for CE, and medication history prospectively. A salicylate spot test
      and gas chromatography-mass spectrometry were performed for NSAID metabolites in
      urine samples of patients undergoing routine CE. Videos were analyzed by a
      gastroenterologist who was blinded to the urinalysis results. RESULTS: Seventy
      six patients (52 women; mean age, 50 y) underwent CE for suspected small-bowel
      pathology. Urinalysis was positive in 13.6% of patients (salicylates, n = 3;
      ibuprofen, n = 6; and ibuprofen and diclofenac, n = 1) although only 1 of these
      patients declared use of an NSAID (aspirin). Although 2 patients had normal CE
      results, 80% had positive results, including the presence of erosions (n = 5),
      ulceration (n = 2), and ulcers with early stricturing (n = 1, diagnosed with
      Crohn's disease). A patient with small-bowel ulceration underwent surgery and was
      found to have NSAID-associated enteropathy, based on histologic analysis.
      CONCLUSIONS: Of patients who undergo CE, 13.6% took NSAIDs or aspirin, but most
      did not declare using these medications. Small-bowel inflammation was common in
      this cohort and could be mistaken for Crohn's disease. Patients should be
      questioned about use of over-the-counter medications, and routine urinalysis for
      NSAID metabolites may be helpful before interpretation of CE findings.

PMID- 20692370
TI  - Gastric electrical stimulation and the "eye of the beholder".

PMID- 20692371
TI  - Predictors of early treatment discontinuation among patients with genotype 1
      hepatitis C and implications for viral eradication.
AB  - BACKGROUND & AIMS: A significant proportion of patients with hepatitis C virus
      (HCV) infection discontinue antiviral treatment prematurely. Risk factors for
      discontinuation before 48 weeks among patients with genotype 1 HCV vary over the
      course of therapy. We investigated the rates and risk factors for treatment
      discontinuation within 12 weeks, 12-24 weeks, and 24-48 weeks. METHODS: We
      retrospectively evaluated data from all Veterans Affairs (VA) patients with
      genotype 1 HCV who initiated pegylated interferon and ribavirin therapy from 2002
      2007 (n = 11,019). We accounted for appropriate discontinuation because of viral
      nonresponse. RESULTS: Overall, 53% of patients completed at least 38.4 weeks of
      therapy (80% of the projected 48 weeks), 16.5% discontinued early in the setting
      of viral nonresponse, and 30.9% discontinued despite viral response or in the
      absence of virologic data. Cirrhosis, diabetes, pretreatment substance use
      disorder, hemoglobin, and lack of hematopoietic growth factor use independently
      predicted discontinuation before 12 weeks (P < .05 for all). Among patients with
      documented early virologic responses, higher baseline levels of creatinine,
      depression, and lack of growth factor use predicted discontinuation from 12-24
      weeks. No factors independently predicted discontinuation from 24-48 weeks among
      patients responding to treatment at 24 weeks. CONCLUSIONS: Early discontinuation
      of antiviral therapy is common. Use of growth factors was the strongest
      independent predictor of treatment retention before 24 weeks and should be
      evaluated prospectively. Early interventions may also be warranted for other risk
      factors for early discontinuation, such as pre-existing substance use,
      depression, cirrhosis, or diabetes.

PMID- 20692372
TI  - Celiac disease and persistent symptoms.

PMID- 20692373
TI  - Emerging nanotechnology approaches in tissue engineering for peripheral nerve
      regeneration.
AB  - Effective nerve regeneration and functional recovery subsequent to peripheral
      nerve injury is still a clinical challenge. Autologous nerve graft
      transplantation is a feasible treatment in several clinical cases, but it is
      limited by donor site morbidity and insufficient donor tissue, impairing complete
      functional recovery. Tissue engineering has introduced innovative approaches to
      promote and guide peripheral nerve regeneration by using biomimetic conduits
      creating favorable microenvironments for nervous ingrowth, but despite the
      development of a plethora of nerve prostheses, few approaches have as yet entered
      the clinic. Promising strategies using nanotechnology have recently been
      proposed, such as the use of scaffolds with functionalized cell-binding domains,
      the use of guidance channels with cell-scale internally oriented fibers, and the
      possibility of sustained release of neurotrophic factors. This review addresses
      the fabrication, advantages, drawbacks, and results achieved by the most recent
      nanotechnology approaches in view of future solutions for peripheral nerve
      repair. FROM THE CLINICAL EDITOR: Peripheral nerve repair strategies are very
      limited despite numerous advances on the field of neurosciences and regenerative
      medicine. This review discusses nanotechnology based strategies including
      scaffolds with functionalized cell binding domains, the use of guidance channels,
      and the potential use of sustained release neurotropic factors.

PMID- 20692374
TI  - Polymer nanoparticles containing tumor lysates as antigen delivery vehicles for
      dendritic cell-based antitumor immunotherapy.
AB  - Encapsulation of tumor-associated antigens in polymer nanoparticles (NP) is a
      promising approach to enhance efficiency of antigen delivery for anti-tumor
      vaccines. Head and neck squamous carcinoma (HNSCC) cell lines were initially used
      to generate tumor-associated antigens (TAA)-containing poly (lactic-co-glycolic
      acid) (PLGA) NP; encapsulation efficiency and release kinetics were profiled.
      Findings were adopted to entrap fresh tumor lysate from five patients with
      advanced HNSCC. To test the hypothesis that NP enhance antigen presentation,
      dendritic cell (DC) produced from patient blood monocyte precursors were loaded
      with either the un-encapsulated or NP-encapsulated versions of tumor lysates.
      These were used to stimulate freshly-isolated autologous CD8+ T cells. In four of
      five patients, anti-tumor CD8+ T cells showed significantly increased
      immunostimulatory IFN-gamma (p=0.071) or decreased immmunoinhibitory IL-10
      production (p=0.0004) associated with NP-mediated antigen delivery. The
      observations represent an enabling step in the production of clinically
      translatable, inexpensive, highly-efficient, and personalized polymer-based
      immunotherapy for solid organ malignancies. FROM THE CLINICAL EDITOR: Enhancing
      the antigen presentation may be a viable approach to increase the efficiency of
      tumor cell directed cytotoxicity via immune mechanisms. This study presents an
      example for this using head and neck cancer cell lines and nanotechnology-based
      encapsulated antigen presentation to dendritic cells. The observed CD8+ T-cell
      response was significantly enhanced. This method may pave the way to a highly
      efficient cancer cell elimination method with minimal to no toxicity.

PMID- 20692375
TI  - Nanosuspension: a new vehicle for the improvement of the delivery of drugs to the
      ocular surface. Application to amphotericin B.
AB  - Present limitations in the management of ophthalmic fungal infections include the
      inability to provide long-term extraocular drug delivery without compromising
      intraocular structures and/or systemic drug exposure. In the present study, the
      potential of Eudragit RS 100 nanoparticles (NPs) as a new vehicle for the
      improvement of the delivery of drugs to the ocular mucosa was investigated.
      Amphotericin B (AmB) was chosen as a model compound because of its potential
      usefulness for the treatment of fungal diseases. A solvent displacement technique
      was used to produce AmB-loaded Eudragit NPs. These NPs had a mean size range of
      150-290 nm and a zeta potential of +19-28 mV. Even after 6 months of stability
      study, results were unchanged, indicating the good potential for ocular
      application. In vitro release studies revealed that a maximum amount of drug was
      released within 24 hours (60%). The results obtained from microbial assay showed
      that the antifungal activity of drug-loaded NPs was equal to or slightly lower
      than that of free-AmB solution. In vivo experiments showed that, following
      topical instillation of nanosuspension to a rabbit's eye there was no irritation.
      From these results we can conclude that Eudragit RS 100 nanosuspension may
      represent an efficacious vehicle to deliver the drug into the eye. FROM THE
      CLINICAL EDITOR: Amphotericin B encapsulated into Eudragit, a mildly cationic
      nanoparticle, was shown to have 6 month stability, release 60% of its drug
      payload in dissolution within 24 hours, and elicited no irritation when instilled
      into rabbit eyes. The concept is being considered for local ophthalmologic
      therapy of fungal disease.

PMID- 20692376
TI  - Pulsed field gel electrophoresis: a review of application and interpretation in
      the molecular epidemiology of infectious disease.
AB  - Over the years, approaches to the epidemiological analysis of infectious disease
      have undergone a remarkable evolutionary transition moving from phenotypic to
      molecular in nature. As discussed here, the quest for a clearer comparison of
      genomic relatedness between bacterial clinical isolates has involved four
      generations of molecular iteration. First generation plasmid analysis gave way to
      a second generation use of restriction enzymes and probes. This was followed by
      third generation pulsed field gel electrophoresis (PFGE) and PCR-based methods
      with movement now to fourth-generation DNA sequence-based approaches. Remarkably,
      despite (or perhaps because of) its more than 20-year history as a typing method,
      PFGE has demonstrated exceptional staying power. The reasons for this endurance
      as well as the pros and cons of PFGE use are examined in this review. In broad
      context the history and technology behind PFGE are considered. Issues commonly
      influencing the quality of PFGE data and its analysis are discussed. Specifics
      regarding the mechanics of DNA preparation, restriction-enzyme digestion, and
      proper conditions for electrophoresis are detailed and, most importantly for any
      approach to epidemiological assessment, issues regarding the analysis and
      interpretation of PFGE data are explored.

PMID- 20692377
TI  - Molecular characteristics of "Mycobacterium canettii" the smooth Mycobacterium
      tuberculosis bacilli.
AB  - Since the first discovery of the smooth tubercle (SmTB) bacilli "Mycobacterium
      canettii" less than 60 isolates have been reported, all but one originating from
      a limited geographical location, the Horn of Africa. In spite of its rarity, the
      SmTB lineage deserves special attention. Previous investigations suggested that
      SmTB isolates represent an ancestral lineage of the Mycobacterium tuberculosis
      complex (MTBC) and that consequently they might provide essential clues on the
      origin and evolution of the MTBC. There is evidence that unlike the rest of the
      MTBC, SmTB strains recombine chromosomal sequences with a yet unknown
      Mycobacterium species. This behavior contributes to the much larger genetic
      heterogeneity observed in the SmTB isolates compared to the other members of the
      MTBC. We have collected 59 SmTB isolates of which 14 were newly recovered since
      previous reports, and performed extensive phenotypical and genotypical
      characterization. We take advantage of these investigations to review the current
      knowledge of "M. canettii". Their characteristics and the apparent lack of human
      to human transmission are consistent with the previously proposed existence of
      non-human sources of infection. SmTB strains show remarkably common features
      together with secondary and taxonomically minor genetic differences such as the
      presence or absence of the CRISPR (Clustered Regularly Interspersed Palindromic
      Repeat) locus (usually called Direct Repeat or DR region) or number of IS
      sequences. Multiple Locus Variable number of tandem repeat Analysis (MLVA) and DR
      region analyses reveal one predominant clone, one minor clone and a number of
      more distantly related strains. This suggests that the two most frequent clones
      may represent successfully emerging lineages.

PMID- 20692379
TI  - Cardiac involvement in systemic rheumatic diseases: An update.
AB  - The high rates of cardiovascular (CV) mortality and morbidity observed in
      patients with systemic autoimmune diseases (SADs) cannot be fully explained by
      traditional atherosclerosis risk factors as standard therapy (i.e.
      corticosteroids and methotrexate), cytokines and disease activity may all
      contribute to accelerated atherosclerosis. There is considerable evidence showing
      that chronic inflammation and immune dysregulation play a pathogenetic role in
      the development of atherosclerosis in patients with SADs. Chronic inflammation,
      accelerated atherosclerosis and functional abnormalities of the endothelium
      suggest that subclinical CV involvement begins soon after the onset of the
      disease and progresses with disease duration. All cardiac structures may be
      affected during the course of SADs (valves, the conduction system, the
      myocardium, endocardium and pericardium, and coronary arteries), and the cardiac
      complications have a variety of clinical manifestations. As these are all
      associated with an unfavourable prognosis, it is essential to detect subclinical
      cardiac involvement in asymptomatic SAD patients, and begin adequate management
      and treatment early.

PMID- 20692378
TI  - First transcriptomic analysis of the economically important parasitic nematode,
      Trichostrongylus colubriformis, using a next-generation sequencing approach.
AB  - Trichostrongylus colubriformis (Strongylida), a small intestinal nematode of
      small ruminants, is a major cause of production and economic losses in many
      countries. The aims of the present study were to define the transcriptome of the
      adult stage of T. colubriformis, using 454 sequencing technology and
      bioinformatic analyses, and to predict the main pathways that key groups of
      molecules are linked to in this nematode. A total of 21,259 contigs were
      assembled from the sequence data produced from a normalized cDNA library; 7876 of
      these contigs had known orthologues in the free-living nematode Caenorhabditis
      elegans, and encoded, amongst others, proteins with 'transthyretin-like' (8.8%),
      'RNA recognition' (8.4%) and 'metridin-like ShK toxin' (7.6%) motifs.
      Bioinformatic analyses inferred that relatively high proportions of the C.
      elegans homologues are involved in biological pathways linked to 'peptidases'
      (4%), 'ribosome' (3.6%) and 'oxidative phosphorylation' (3%). Highly represented
      were peptides predicted to be associated with the nervous system, digestion of
      host proteins or inhibition of host proteases. Probabilistic functional gene
      networking of the complement of C. elegans orthologues (n=2126) assigned
      significance to particular subsets of molecules, such as protein kinases and
      serine/threonine phosphatases. The present study represents the first,
      comprehensive insight into the transcriptome of adult T. colubriformis, which
      provides a foundation for fundamental studies of the molecular biology and
      biochemistry of this parasitic nematode as well as prospects for identifying
      targets for novel nematocides. Future investigations should focus on comparing
      the transcriptomes of different developmental stages, both genders and various
      tissues of this parasitic nematode for the prediction of essential genes/gene
      products that are specific to nematodes.

PMID- 20692380
TI  - Usefulness of cardiovascular biomarkers and cardiac imaging in systemic rheumatic
      diseases.
AB  - Systemic rheumatic diseases (SRDs) are associated with accelerated
      atherosclerosis. It has recently been recognised that chronic inflammation is an
      important factor in the development of atherosclerotic plaque and endothelial
      dysfunction. The levels of biomarkers such as serum pentraxin 3 (PTX3), an innate
      immunity protein, and asymmetric dimethylarginine (ADMA), an endogenous inhibitor
      of NO synthase, are higher in SRD  patients with cardiovascular (CV) disease and
      are now recognized as new CV risk factors. Many diagnostic methods and imaging
      techniques detect subtle pre-clinical CV abnormalities in SRD patients, although
      their clinical significance has not yet been established in patients.
      Echocardiographic examinations based on the evaluation of coronary flow reserve
      (CFR), tissue Doppler imaging (TDI) and speckle tracking echocardiography (STE)
      seem to be the most suitable means of screening and diagnosis. Furthermore,
      plasma ADMA levels could be used as a simple means of screening SRD patients at
      higher CV risk who need more aggressive treatment aimed at slowing or reversing
      the progression of atherosclerosis.

PMID- 20692381
TI  - IL-1beta acutely increases pulmonary SP and permeability without associated
      changes in airway resistance and ventilation in anesthetized rats.
AB  - Bronchopulmonary C-fibers (PCFs), when activated, promote substance P (SP)
      release, increase microvascular leak, and produce bronchoconstriction and apnea.
      IL-1beta administered systemically or locally into the pulmonary parenchyma
      stimulates PCFs. Thus, we tested whether right atrial bolus injection or aerosol
      inhalation of IL-1beta, to mainly stimulate PCFs, would acutely affect pulmonary
      SP level and vascular permeability, airway resistance (R(L)), and ventilation in
      anesthetized rats. Our results showed that 30min after IL-1beta injection (2-6
      MUg kg-1), SP levels and Evans blue extravasation in bronchoalveolar lavage fluid
      were markedly increased and these responses were eliminated or largely reduced in
      neonatal capsaicin-treated rats. In contrast, neither injection nor inhalation of
      IL-1beta (5-15 MUg ml-1) significantly altered R(L) and ventilation.
      Additionally, the capsaicin-evoked (4 MUg kg-1, i.v.) apneic response was
      unaffected by IL-1beta treatment. Our data suggest that IL-1beta, as administered
      in this study, can acutely increase pulmonary SP and vascular permeability,
      likely via stimulating PCFs, with little impact on R(L) and ventilation.

PMID- 20692382
TI  - Evaluation of respiratory muscle activation in individuals with chronic spinal
      cord injury.
AB  - This study was undertaken to physiologically characterize respiratory muscle
      control in eighteen individuals with spinal cord injury (SCI) through comparison
      with 14 matched non-injured (NI) subjects. Standard pulmonary function measures
      (FVC, FEV(1), PI(max) and PE(max)) were obtained along with surface
      electromyographic (sEMG) recording from respiratory muscles. A vector analysis of
      sEMG was used to calculate Similarity Index (SI) values relating SCI subject sEMG
      patterns to those produced by NI subjects. SI values for inspiratory and
      expiratory tasks were very consistent within the NI group, 0.92+/-0.03 and 0.93+/
      0.04 (mean+/-SD), respectively. Altered multi-muscle patterns in the SCI group
      produced SI values that trended lower 0.84+/-0.11 for inspiratory tasks and were
      significantly lower, 0.59+/-0.22 for expiratory tasks. SI values for expiratory
      tasks were also significantly correlated with SCI levels and pulmonary function
      measures. These results suggest that pulmonary function after SCI is dependent
      upon the degree to which multi-muscle activation patterns are disrupted.

PMID- 20692383
TI  - Conformational and biochemical characterization of a rat epididymis-specific
      lipocalin 12 expressed in Escherichia coli.
AB  - Lipocalin 12 (Lcn12) is a recently identified epididymis-specific protein that
      might play a significant physiological role in male reproduction. However, the
      detailed structure and function of Lcn12 remain to be determined. In the present
      work, we cloned, expressed, and purified the rat Lcn12 (rLcn12) protein in
      Escherichia coli, introduced the Cys176Ala substitution to eliminate the
      aggregation problem associated with the wild-type protein. Homology modeling
      results demonstrated that rLcn12 adopted an eight-stranded, antiparallel beta
      barrel conformation containing a conserved disulfide bond between Cys98 and
      Cys203, which was in accordance with the physicochemical properties elucidated by
      a combination of mass, circular dichroism, and nuclear magnetic resonance
      spectrometry. The purified rLcn12 protein exhibited a high binding affinity for
      all-trans retinoic acid in fluorescence titration experiments, implying that
      rLcn12 could be involved in retinoic acid transport in the epididymis.

PMID- 20692384
TI  - Pre-osteoblasts on poly(L-lactic acid) and silicon oxide: Influence of
      fibronectin and albumin adsorption.
AB  - Cell adhesion and subsequent viability are critical initial steps in biomaterial
      tissue integration and are strongly dependent on the material properties and the
      presence of matrix proteins. In the present study MC3T3-E1 osteoblast-like cell
      behavior on silicon oxide (SO) and poly(L-lactic acid) (PLLA) substrates has been
      examined, with a focus on the influence of the adhesive protein fibronectin and
      the non-adhesive protein albumin adsorbed on the substrates. Quartz crystal
      microgravimetry showed adsorption of fibronectin and albumin to be nearly
      identical on SO and PLLA. Subsequent exposure a previously adsorbed fibronectin
      layer to albumin decreased the rigidity of the adsorbed layer without any
      measurable increase in adsorbed mass. Cell adhesion and spreading were
      significantly enhanced on both SO and PLLA substrates coated with fibronectin or
      with fibronectin and albumin, compared with uncoated or albumin-coated
      substrates. The only statistically significant difference between the two
      substrates in these assays was increased spreading on PLLA compared with SO in
      the presence of fibronectin and albumin. Cell proliferation was significantly
      higher on SO compared with PLLA after 7 days culture, but depended on the
      presence of fibronectin only in the PLLA system. In contrast, mitochondrial
      activity was higher on PLLA than on SO, and was enhanced by fibronectin on both
      substrates. PLLA substrates coated with fibronectin and subsequently exposed to
      albumin exhibited the highest level of cell differentiation, as assayed via
      alkaline phosphatase activity. These results demonstrate the importance of
      adsorbed proteins on osteoblast-like cell-surface interactions.

PMID- 20692385
TI  - Identification of luminal and secreted proteins in bull epididymis.
AB  - The epididymis plays a major role in the acquisition of sperm fertility. In order
      to shed light on specific features of epididymal function in mammalian species,
      we characterized the luminal proteins (luminal proteome) and secreted proteins
      (secretome) in the bovine epididymis. We identified 172 different luminal
      proteins in 9 distinct epididymal regions. The concentration and secretory
      activity of luminal proteins were quantified throughout the epididymis. Among the
      most abundant secreted proteins, we found lipocalin 5, (LCN5), NADP(+)dependent
      prostaglandin dehydrogenase (PTGDS), Niemann-Pick disease type C2 protein (NPC2),
      glutathione peroxidase type 5 (GPX 5), clusterin (CLU), hexosaminidase B (HEXB)
      and galactosidase (GLB1), each of which is released in distinct epididymal
      regions. Gelsolin, (GSN) previously not described in mammalian epididymal fluid,
      appeared to be a major protein secreted exclusively in the distal region of the
      bovine epididymis, where fully mature spermatozoa are stored. Although the major
      epididymal proteins are conserved between mammalian species, this study
      highlights the specificity and mechanisms of protein processing of epididymal
      secretion in the bull. In addition, this study provides a major insight into the
      sequential changes occurring in the sperm environment while gaining fertilizing
      capacity and could provide new information for the future identification of
      potential fertility markers.

PMID- 20692386
TI  - Arabidopsis thaliana as a model organism for plant proteome research.
AB  - Genome sequencing and systems biology revolutionized life sciences. Proteomics
      emerged as a fundamental technique of this novel research area. This review aims
      to summarize the contribution of Arabidopsis thaliana as a model organism for
      plants and the increasing impact of proteome research. Techniques for proteomics
      based on 2-DE and especially gel-free shotgun LC-MS/MS platforms have improved
      significantly during the last decades. Proteomics has proven to be complementary
      to other -omics techniques such as transcriptomics and metabolomics. Arabidopsis
      thaliana as one of the first model organisms worldwide, served in several of the
      most comprehensive studies for enhance genome annotation, profiling of
      organelles, tissues, cells or sub-cellular proteomes, as well as developmental
      processes and responses to biotic and abiotic stresses using differential
      relative and absolute quantitative strategies. Consequently, insights into plant
      proteome dynamics and cell functions are rapidly increasing. A proteomics-toolbox
      developed for systems biology research on Arabidopsis will be introduced.

PMID- 20692387
TI  - Current status of cancer proteomics, how far are we from clinical applications?

PMID- 20692389
TI  - HR-pQCT based FE analysis of the most distal radius section provides an improved
      prediction of Colles' fracture load in vitro.
AB  - The remarkable performances of high-resolution peripheral quantitative computed
      tomography (HR-pQCT) make the distal radius a favorable site for early diagnosis
      of osteoporosis and improved Colles' fracture risk assessment. The goal of this
      study was to investigate if the HR-pQCT-based micro finite element (MUFE) method
      applied on specific sections of the distal radius provides improved predictions
      of Colles' fracture load in vitro compared to bone mineral content (BMC), bone
      mineral density (BMD), or histomorphometric indices. HR-pQCT based BMC, BMD,
      histomorphometric parameters, and MUFE models of 9-mm-thick bone sections were
      used to predict fracture load of 21 distal radii assessed in an experimental
      model of Colles' fracture reported in a previous study. The analysis was
      performed on two bone sections: a standard one recommended by the HR-pQCT
      manufacturer and a second one defined just proximal to the distal subchondral
      plate. For most of the investigated parameters, significant differences were
      found between the values of the two sections. Correlations with experimental
      fracture load and strength were higher in the most distal section, and the
      difference was statistically significant for MUFE strength. Furthermore, the most
      distal section was computed to have significantly lower ultimate force and
      strength by 13% and 35%, respectively, than the standard section. BMC provided a
      better estimation of Colles' fracture load (R(2)=0.942) than aBMD or any other
      histomorphometric indices. The best prediction was achieved with MUFE analyses of
      the most distal slice (R(2)=0.962), which provided quantitatively correct
      ultimate forces.

PMID- 20692388
TI  - Deciphering the iron response in Acinetobacter baumannii: A proteomics approach.
AB  - Iron is an essential nutrient that plays a role in bacterial differential gene
      expression and protein production. Accordingly, the comparative analysis of total
      lysate and outer membrane fractions isolated from A. baumannii ATCC 19606(T)
      cells cultured under iron-rich and -chelated conditions using 2-D gel
      electrophoresis-mass spectrometry resulted in the identification of 58 protein
      spots differentially produced. While 19 and 35 of them represent iron-repressed
      and iron-induced protein spots, respectively, four other spots represent a metal
      chelation response unrelated to iron. Most of the iron-repressed protein spots
      represent outer membrane siderophore receptors, some of which could be involved
      in the utilization of siderophores produced by other bacteria. The iron-induced
      protein spots represent a wide range of proteins including those involved in iron
      storage, such as Bfr, metabolic and energy processes, such as AcnA, AcnB, GlyA,
      SdhA, and SodB, as well as lipid biosynthesis. The detection of an iron-regulated
      Hfq ortholog indicates that iron regulation in this bacterium could be mediated
      by Fur and small RNAs as described in other bacteria. The iron-induced production
      of OmpA suggests this protein plays a role in iron metabolism as shown by the
      diminished ability of an isogenic OmpA deficient derivative to grow under iron
      chelated conditions.

PMID- 20692390
TI  - Re-reading Nightingale: Notes on Hospitals.

PMID- 20692391
TI  - Similar early complication rate in simultaneous pancreas and kidney recipients on
      tacrolimus/mycophenolate mofetil versus tacrolimus/sirolimus immunosuppressive
      regimens.
AB  - INTRODUCTION: We compared the incidence of severe complications among 123
      consecutive simultaneous pancreas and kidney (SPK) recipients randomized for
      treatment either with tacrolimus plus mycophenolate mofetil (MMF) or tacrolimus
      plus sirolimus during their initial postoperative hospital stay. METHODS:
      Patients with type 1 diabetes mellitus (T1DM) and renal failure with no age limit
      who underwent SPK were randomly assigned to tacrolimus/sirolimus or
      tacrolimus/MMF immunosuppressive protocols. We analyzed the rate of adverse
      events that led to death, graft loss, operative revision, or prolonged hospital
      stay. RESULTS: From 2002 to 2009, 62 recipients were included in the MMF and 61
      in the Rapamycin (Rapa) groups. More than 2/3 of recipients suffered from at
      least 1 complication: 74% MMF and 77 % Rapa group (P > .05). No patient died in
      the MMF and 3 in the Rapa group (P = .11). Pancreas graftectomy was performed in
      13% of the MMF group and in 5% of the Rapa group (P = .20). Ten of 62 recipients
      in the MMF and 13/61 in the Rapa group required operative treatment of wound
      infections (P = .49). There were no differences in the rates of gastrointestinal
      bleeding (11% and 8%), kidney lymphocele (6% and 5%), ileus (1.6% both),
      pancreatic leak (1.6% both), or ureteral leak (0 and 3%) between the groups.
      CONCLUSION: We did not observe a difference in the rate of severe postoperative
      complications between groups. With the use of extraperitoneal placement of the
      pancreatic graft, fluid collections and wound infections remain the most frequent
      albeit curable postoperative complications.

PMID- 20692392
TI  - Anti-CD25 antibody (daclizumab) maintenance therapy in pancreas transplantation.
AB  - BACKGROUND: Calcineurin inhibitors (CNI) are the basis of contemporary
      immunosuppression in clinical pancreas transplantation (PT). Nevertheless, CNI
      toxicities, especially nephrotoxicity, have stimulated the search for CNI-sparing
      protocols. We performed a retrospective analysis of 25 PT patients with
      progressive CNI toxicities that were switched to a daclizumab (DAC)-based
      maintenance regimen. METHODS: From 2003 to 2007, 25 PT patients with progressive
      CNI toxicity (predominantly nephrotoxicity) were identified and switched from CNI
      to monthly DAC maintenance therapy. The DAC group was compared with matched
      control subjects (1:1) by transplant type and number, age, year of transplant,
      and duct management. RESULTS AND CONCLUSIONS: Results showed improved graft
      survival rates and decreased immunologic loss rates at 1, 3, and 5 years in the
      DAC group compared with the control group. There was no difference in patient
      survival rate between the 2 groups. Analysis demonstrates that DAC maintenance
      therapy is safe and effective for PT patients experiencing CNI toxicities. A
      randomized trial to compare DAC- and CNI-based regimens is needed in CNI
      intolerant patients, with particular attention to the impact on renal function
      and patient morbidity (eg, infection rates).

PMID- 20692393
TI  - Alemtuzumab with rapid steroid taper in simultaneous kidney and pancreas
      transplantation: comparison to induction with antithymocyte globulin.
AB  - We compared our experience with alemtuzumab induction and rapid steroid taper
      (RST) in simultaneous kidney and pancreas transplantation (SKPT) with a historic
      control group who received rabbit antithymocyte globulin (r-ATG) induction with
      RST. 74 SKPTs performed at our center between January 2005 to November 2008 who
      underwent immunosuppression with RST in combination with r-ATG induction (n = 33;
      1.5 mg/kg x 4 for a total dose of 6 mg/kg) or alemtuzumab induction (n = 41; 30
      mg single dose). Maintenance immunosuppression consisted of tacrolimus and
      mycophenolate mofetil. Steroids were discontinued after postoperative day 4.
      Recipient and transplant characteristics were similar between the 2 groups, with
      82% of the r-ATG and 80% of the alemtuzumab group steroid free at 1 year. The
      rate of clinical acute rejection episodes was 12% in the r-ATG group and 15% in
      the alemtuzumab group. The rates of cytomegalovirus (CMV) infection, BK
      nephropathy, and graft survival were similar between the 2 groups. There was no
      difference in mean serum creatinine, calculated GFR, or fasting blood sugar at 1
      year between the 2 groups, whereas glycosylated hemoglobin (HbA1c) was lower at 1
      year in the alemtuzumab (5.3 +/- 0.4) versus the r-ATG group (5.6 +/- 0.4; P =
      .0021). Induction with r-ATG or alemtuzumab with RST was safe and effective in
      SKPT. The incidences of acute rejection episodes, CMV infection, and BK
      nephropathy were similar. Mean HbA1C at 1 year was lower among the alemtuzumab
      group. Further long-term follow-up is needed to confirm these results.

PMID- 20692394
TI  - Simultaneous pancreas and kidney transplantation with concurrent allograft
      nephrectomy for recipients with prior renal transplants lost to BK virus
      nephropathy: two case reports.
AB  - Candidacy for retransplantation after allograft loss due to BK virus-associated
      nephropathy (BKVN) with or without allograft nephrectomy is controversial. This
      report describes 2 renal transplant recipients who lost their grafts to BKVN and
      subsequently underwent simultaneous kidney and pancreas transplantation with
      allograft nephrectomy.

PMID- 20692395
TI  - Pancreas oxygen persufflation increases ATP levels as shown by nuclear magnetic
      resonance.
AB  - BACKGROUND: Islet transplantation is a promising treatment for type 1 diabetes.
      Due to a shortage of suitable human pancreata, high cost, and the large dose of
      islets presently required for long-term diabetes reversal; it is important to
      maximize viable islet yield. Traditional methods of pancreas preservation have
      been identified as suboptimal due to insufficient oxygenation. Enhanced oxygen
      delivery is a key area of improvement. In this paper, we explored improved oxygen
      delivery by persufflation (PSF), ie, vascular gas perfusion. METHODS: Human
      pancreata were obtained from brain-dead donors. Porcine pancreata were procured
      by en bloc viscerectomy from heparinized donation after cardiac death donors and
      were either preserved by either two-layer method (TLM) or PSF. Following
      procurement, organs were transported to a 1.5-T magnetic resonance (MR) system
      for (31)P nuclear magnetic resonance spectroscopy to investigate their
      bioenergetic status by measuring the ratio of adenosine triphosphate to inorganic
      phosphate (ATP:P(i)) and for assessing PSF homogeneity by MRI. RESULTS: Human and
      porcine pancreata can be effectively preserved by PSF. MRI showed that pancreatic
      tissue was homogeneously filled with gas. TLM can effectively raise ATP:P(i)
      levels in rat pancreata but not in larger porcine pancreata. ATP:P(i) levels were
      almost undetectable in porcine organs preserved with TLM. When human or porcine
      organs were preserved by PSF, ATP:P(i) was elevated to levels similar to those
      observed in rat pancreata. CONCLUSION: The methods developed for human and
      porcine pancreas PSF homogeneously deliver oxygen throughout the organ. This
      elevates ATP levels during preservation and may improve islet isolation outcomes
      while enabling the use of marginal donors, thus expanding the usable donor pool.

PMID- 20692396
TI  - Persufflation improves pancreas preservation when compared with the two-layer
      method.
AB  - Islet transplantation is emerging as a promising treatment for patients with type
      1 diabetes. It is important to maximize viable islet yield for each organ due to
      scarcity of suitable human donor pancreata, high cost, and the large dose of
      islets required for insulin independence. However, organ transport for 8 hours
      using the two-layer method (TLM) frequently results in low islet yields. Since
      efficient oxygenation of the core of larger organs (eg, pig, human) in TLM has
      recently come under question, we investigated oxygen persufflation as an
      alternative way to supply the pancreas with oxygen during preservation. Porcine
      pancreata were procured from donors after cardiac death and preserved by either
      TLM or persufflation for 24 hours and subsequently fixed. Biopsies collected from
      several regions of the pancreas were sectioned, stained with hematoxylin and
      eosin, and evaluated by a histologist. Persufflated tissues exhibited distended
      capillaries and significantly less autolysis/cell death relative to regions not
      exposed to persufflation or to tissues preserved with TLM. The histology
      presented here suggests that after 24 hours of preservation, persufflation
      dramatically improves tissue health when compared with TLM. These results
      indicate the potential for persufflation to improve viable islet yields and
      extend the duration of preservation, allowing more donor organs to be utilized.

PMID- 20692397
TI  - Continuous real-time viability assessment of kidneys based on oxygen consumption.
AB  - BACKGROUND: Current ex vivo quality assessment of donor kidneys is limited to
      vascular resistance measurements and histological analysis. New techniques for
      the assessment of organ quality before transplantation may further improve
      clinical outcomes while expanding the depleted deceased-donor pool. We propose
      the measurement of whole organ oxygen consumption rate (WOOCR) as a method to
      assess the quality of kidneys in real time before transplantation. METHODS: Five
      porcine kidneys were procured using a donation after cardiac death (DCD) model.
      The renal artery and renal vein were cannulated and the kidney connected to a
      custom-made hypothermic machine perfusion (HMP) system equipped with an inline
      oxygenator and fiber-optic oxygen sensors. Kidneys were perfused at 8 degrees C,
      and the perfusion parameters and partial oxygen pressures (pO(2)) were measured
      to calculate WOOCR. RESULTS: Without an inline oxygenator, the pO(2) of the
      perfusion solution at the arterial inlet and venous outlet diminished to near 0
      within minutes. However, once adequate oxygenation was provided, a significant
      pO(2) difference was observed and used to calculate the WOOCR. The WOOCR was
      consistently measured from presumably healthy kidneys, and results suggest that
      it can be used to differentiate between healthy and purposely damaged organs.
      CONCLUSIONS: Custom-made HMP systems equipped with an oxygenator and inline
      oxygen sensors can be applied for WOOCR measurements. We suggest that WOOCR is a
      promising approach for the real-time quality assessment of kidneys and other
      organs during preservation before transplantation.

PMID- 20692398
TI  - Improved method of human islet isolation for young donors.
AB  - BACKGROUND: Although islet transplantation using young donors is more effective
      than older donors, islet isolation from young donor is notoriously difficult.
      This may relate to islet ontogeny and collagen composition in the young pancreas.
      Therefore, we examined whether a high concentration of collagenase could improve
      the separation of islets from exocrine tissues resulting in an high islet yield.
      METHODS: We used six human pancreata from brain-dead donors of less than 30 years
      old. Islet isolation was performed based on the Edmonton protocol with
      modifications. All pancreata were digested with Collagenase NB1 Premium Grade
      (Serva). The pancreas was expanded by injecting either 200 mL of cold collagenase
      solution (2.5 mg/mL, standard group, n = 3) or 100 mL of solution (5 mg/mL, new
      group, n = 3) in a controlled manner under low pressure for 5 minutes. Then the
      pressure was raised for another 5 minutes. The following procedure and evaluation
      were performed based on the Edmonton protocol. RESULTS: Phase II time in the new
      group was significantly shorter than the standard group. The ratio of embedded
      islets in the new group was significantly lower than the standard group. The
      postpurification islet equivalents per pancreas weight (IEQ/g) and the recovery
      rate in the new group were higher than the standard group, but not significantly.
      There was no significant difference in the postpurification purity, viability,
      and final tissue volume. CONCLUSION: Our simple modification with an initially
      concentrated collagenase preparation using a syringe significantly improved the
      ratio of embedded islets, resulting in a higher yield from young donors.

PMID- 20692399
TI  - Islet isolation from human pancreas with extended cold ischemia time.
AB  - The general consensus among transplant centers is that a cold ischemia time (CIT)
      beyond 8 hours results in reduced yields and quality of human islets. We sought
      to optimize the isolation process and enzymes for pancreata with extended CIT. We
      processed 16 extended CIT pancreata (13.2 +/- 0.7 hours). Donors averaged 50.8 +/
      2.6 (standard error of the mean) years old with a body mass index of 28.6 +/-
      1.5. Glands were shipped in cold organ preservation solution without oxygenated
      perfluorocarbon. Isolations were performed under a protocol optimized for
      digestion with the new cGMP collagenase from Roche. Purification used continuous
      Euroficoll/University of Wisconsin gradients. Islets were cultured in two types
      of Prodo cGMP islet culture media and/or in Miami 1A media. Glucose-stimulated
      insulin secretion assays were performed after 8 to 16 days of culture.
      Prepurification yield averaged 415 +/- 41 KIEQ postpurification, 359 +/- 29 KIEQ
      (purification loss 13.5%); and postculture 317 +/- 27 KIEQ (culture loss 11.7%).
      Our process liberated an average of 4278 IEQ/g of pancreas (97 +/- 5 g). Most
      islets were recovered in the purest fraction (purity 79.7% +/- 1.9%). Culture
      loss in our enhanced culture media was 11.7%. After 2 to 3 days in culture,
      viability was 92% +/- 1%. Islets exhibited compactness and dithizone staining.
      Glucose-stimulated insulin secretion assays performed after 3 to 23 days in our
      PIM(R) media resulted in a stimulation index of 6.8 +/- 1.7 (G50 to G350). We
      concluded that our human islet isolation process permitted the recovery of large
      numbers of high-quality human islets from extended CIT pancreata and that our
      cGMP islet culture media was superior to the current standard CMRL-based media.

PMID- 20692401
TI  - Rapid quantitative assessment of the pig pancreas biopsy predicts islet yield.
AB  - BACKGROUND: The cost of islet procurement from donor pigs is increased by the use
      of organs that produce low yields. We developed an assessment system using
      dithizone-stained pig pancreas biopsies to enable the preselection of donor
      organs. METHODS: Pig pancreas biopsy slices were soaked in dithizone solution.
      The islets were evaluated before islet isolation by converting the islet counts
      (IC) to islet equivalents (IE), and then determining the IE/cm(2), IE/IC, %
      islets >150 microm, and % islets >200 microm. These parameters were evaluated in
      3 different areas of the pancreas (duodenal, splenic, and connecting lobe; n = 42
      each). Stepwise multivariate linear regression analysis was performed to assess
      for correlations with islet yield and decide which area of the pancreas had the
      most predictive value. To identify other predictors, including donor and islet
      isolation variables, we performed binary logistic regression analysis with
      significant variables from the univariate analysis (n = 67). For this analysis,
      the pigs were categorized into high (n = 23) and low (n = 44) yield groups.
      RESULTS: Stepwise multivariate linear regression analysis revealed that IE/cm(2)
      of the splenic lobe significantly predicted islet yield. Binary logistic
      regression analysis indicated that the IE/mm(2) of the splenic lobe was the only
      parameter that significantly correlated with successful pig islet isolations (P =
      .01; odds ratio 3.605). Variables associated with donor and islet isolation, such
      as age, gender, ischemic time, or enzyme lot, were not significantly correlated
      with islet yield. CONCLUSION: Our study suggests that the islet distribution of
      splenic lobe biopsies can be a reliable predictor of islet yield from pig
      pancreata.

PMID- 20692400
TI  - Improved method of porcine pancreas procurement with arterial flush and ductal
      injection enhances islet isolation outcome.
AB  - BACKGROUND: Several pancreas procurement procedures have been used for porcine
      islet isolation; however, their impact on outcomes has not been extensively
      studied. We evaluated an advanced procurement technique for porcine islet
      isolation designed to reduce warm ischemia, to remove blood content, and enhance
      cooling of the pancreas by implementing a vascular flush and ductal preservation.
      METHOD: Pancreata procured from adult Landrace pigs were divided into 3 different
      surgical protocols: Pancreatectomy utilizing only surface cooling (group 1; n =
      24); surface cooling and ductal injection with cold preservation solution before
      pancreatectomy (group 2; n = 12); or surface cooling, ductal injection, and an
      approach by selectively flushing through the celiac trunk and the superior
      mesenteric artery (group 3; n = 14). We assessed the islet isolation results and
      quality using in vitro and in vivo assays. RESULTS: Significantly higher overall
      yield and islet yield per gram pancreas were obtained from group 3 pigs compared
      with the other groups. Measurements of islet viability after 7 days of culture,
      as assessed by oxygen consumption rate per DNA, showed that group 3 islets
      displayed the highest values. Sustained normoglycemia was observed in diabetic
      nude mice transplanted with 2000 islet equivalents from all 3 groups. DISCUSSION:
      This study demonstrated that an advanced pancreas procurement technique including
      ductal preservation and selective arterial flush with cold preservation solution
      provided significant improvements in porcine islet isolation outcomes.

PMID- 20692402
TI  - The impact of ischemic stress on the quality of isolated pancreatic islets.
AB  - BACKGROUND: Although the ischemic stress of donated organs has been shown to have
      strong negative effects on islet recovery, the impact on islet quality remains
      uncertain. In the present study, therefore, we examined the influence of ischemic
      stress on the expression of inflammatory mediators among isolated islets.
      MATERIALS AND METHODS: Islets were isolated from adult porcine pancreata
      subjected to 16-hour cold ischemia time (CIT) in addition to 40-minute warm
      ischemia time (WIT). We evaluated the islet yield, islet loss during the first 24
      hours in culture, adenosine diphosphate (ADP)/adenosine triphosphate (ATP) ratio,
      ATP/DNA ratio, glucose-stimulated respiratory activity, in vivo bioassay, and the
      expression of inflammatory mediators (tissue factor [TF], [MCP-1], macrophage
      migration inhibitory factor) on the isolated islets. We also analyzed ATP/DNA
      ratios of the exocrine tissues during isolation procedures. RESULTS: The islet
      yield, survival rate during culture, and glucose-stimulated respiratory activity
      were significantly lower in cases of 16-hour CIT plus 40-minute WIT compared with
      the control group (P < .0001, .0006, and .002, respectively). In contrast,
      ADP/ATP ratio as well as TF and MCP-1 expressions on the isolated islets were
      higher among the ischemic group (P = .005, .16, and .005, respectively). During
      isolation procedures, the ATP/DNA of the exocrine tissues was extremely lower in
      the ischemic compared to the control group (P < .0001). Notably, however, both
      ATP/DNA and ADP/ATP ratio of isolated islets were well preserved even in the
      ischemic group (P = .45 and .40). DISCUSSION: These data suggest that ischemic
      stress during the preservation period negatively affects the energy status of
      exocrine tissues. Destruction of the exocrine tissues, in combination with warm
      ischemic stress during the isolation procedures, subsequently decreases isolated
      islet activity, inducing the expression of inflammatory mediators.

PMID- 20692403
TI  - A new method to value efficiency of enzyme blends for pancreatic tissue
      digestion.
AB  - Islet transplantation, since the 1990s, has been an example of human cell
      therapy. Nevertheless, the islet isolation procedure is not completely
      standardized; in fact, >50% of islet procedures do not eventuate in
      transplantation due both to the variability of a donor's pancreas and to the
      unpredictable efficiency of an enzymatic blend. The enzymes used in pancreas
      isolation to digest several substrates are extracted from Clostridium
      histolyticum. In particular, they have strong collagenolytic activity compared
      with vertebrate collagenases. However, several impediments persist in human islet
      isolation success, probably owing to the variable composition and concentration
      of collagenases employed during the digestion phase. For islet isolation
      processes, neutral proteases play important roles. However, they should be
      considered to be double-edged swords, contributing to tissue dissociation but,
      sometimes, decreasing islet yield through fragmentation, breakdown, and
      inactivation. Protease activities cannot be preciously adjusted in a narrow
      range, there is no approach to determine the optimal dosage and composition of
      enzymes for extraction of human islets from the pancreas. At this time, available
      data on commercial enzymatic activity are not sufficient to predict their
      efficiency for pancreas digestion; consequently, it is difficult to select enzyme
      batches. For these reasons, we sought to generate an innovative evaluation assay
      to select enzymes useful for isolation procedures of pancreatic islets.

PMID- 20692404
TI  - Assessment of human islet isolation with four different collagenases.
AB  - BACKGROUND: The isolation of islets from the human pancreas critically depends on
      the efficiency of the digestive enzymes. Liberase HI had been used as a standard
      preparation until the issues concerning bovine spongiform encephalopathy. Thus,
      we must now use other collagenases for clinical islet transplantation, four of
      which we have evaluated herein. METHODS: The digestion of each of 17 pancreata
      from brain-dead donors was performed using the following collagenases: Liberase
      HI (HI; Roche, n = 9); Liberase MTF C/T (MTF; Roche, n = 4); Collagenase NB1
      Premium Grade (NB1; Serva, n = 7); or Clzyme Collagenase HA (CI, VitaCyte, n =
      4). Islet isolations were based on the Edmonton protocol for HI, whereas our
      modified islet isolation method was used for the three new enzymes (MTF, NB1, and
      CI). RESULTS: There were no significant differences in donor age, body mass
      index, pancreas size, and cold ischemic time among the four groups. The phase I
      time in the NB1 group was significantly shorter than in the CI group (P = .0014).
      The prepurification IEQ/g in the HI group was significantly lower than the others
      (P = .0003 vs MTF, .0007 vs NB1, and .0009 vs CI, respectively). The
      postpurification IEQ/g in the MTF group was significantly higher than in the HI
      group (P = .006). The viability in the NB1 group was significantly greater than
      the HI group (P = .003). CONCLUSION: Three new enzymes (MTF, NB1, and CI) may
      enable us to obtain higher islet yields than with HI.

PMID- 20692405
TI  - Tissue dissociation enzyme neutral protease assessment.
AB  - Neutral proteases, essential components of purified tissue dissociation enzymes
      required for successful human islet isolation, show variable activities and
      effects of substrate on their activities. Initially we used a spectrophotometric
      endpoint assay with azocasein substrate to measure neutral protease activity.
      After critical review of the results, we observed these data to be inconsistent
      and not correlating expected differences in specific activities between
      thermolysin and Bacillus polymyxa proteases. This observation led to the
      development of a fluorescent microplate assay using fluorescein isothyocyanate
      conjugated bovine serum albumin (FITC-BSA) as the substrate. This simpler, more
      flexible method offered a homogeneous, kinetic enzyme assay allowing
      determination of steady state reaction rates of sample replicates at various
      dilutions. The assay had a linear range of 4- to 8-fold and interassay
      coefficients of variation for B polymyxa protease and thermolysin of <9% and
      <15%, respectively, which were lower than those using the spectrophotometric
      endpoint assay, namely, 54% and 36%, respectively. This format allowed for
      incorporation of enzyme inhibitors, as illustrated by addition of sulfhydryl
      protease inhibitors, which, consistent with earlier reports, strongly indicated
      that the main contaminant in purified collagenase preparations was clostripain.
      Determination of the specific activities for several purified neutral proteases
      showed that the B polymyxa and Clostridium histolyticum proteases had
      approximately 40% and 15% specific activities, respectively, of those obtained
      with purified thermolysin, indicating the different characteristics of neutral
      protease enzymes for cell isolation procedures.

PMID- 20692406
TI  - Culture of impure human islet fractions in the presence of alpha-1 antitrypsin
      prevents insulin cleavage and improves islet recovery.
AB  - BACKGROUND: Exocrine tissue is commonly cotransplanted with islets in
      autografting and allotransplantation of impure preparations. Proteases and
      insulin are released by acinar cells and islets, respectively, during
      pretransplantation culture and also systemically after transplantation. We
      hypothesized that released proteases could cleave insulin molecules and that
      addition of alpha-1 antitrypsin (A1AT) to impure islet cultures would block this
      cleavage, improving islet recovery and function. METHODS: Trypsin, chymotrypsin,
      and elastase (TCE) activity and insulin levels were measured in culture
      supernates of pure (n = 5) and impure (n = 5) islet fractions, which were
      isolated from deceased donors. Sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE) was used to detect insulin after incubation with
      proteases. We assessed the effects of A1AT supplementation (0.5 mg/mL; n = 4] on
      TCE activity, insulin levels, culture recovery, and islet quality. The
      ultrastructure of islets exposed to TCE versus control medium was examined using
      electron microscopy (EM). RESULTS: Protease (TCE) activity in culture
      supernatants was indirectly proportional to the percentage purity of islets:
      pure, impure, or highly impure. Increasingly lower levels of insulin were
      detected in culture supernatants when higher protease activity levels were
      present. Insulin levels measured from supernatants of impure and highly impure
      islet preparations were 61 +/- 23.7% and 34 +/- 33% of that in pure preparations,
      respectively. Incubation with commercially available proteases (TCE) or exocrine
      acinar cell supernatant cleaved insulin molecules as assessed using SDS-PAGE.
      Addition of A1AT to impure islet preparations reduced protease activity and
      restored normal insulin levels as detected using enzyme-linked immunosorbent
      assay (ELISA) and SDS-PAGE of culture supernates. A1AT improved insulin levels to
      98% +/- 1.3% in impure and 78% +/- 34.2% in highly impure fractions compared with
      pure islet fractions. A1AT supplementation improved postculture recovery of
      islets in impure preparations compared with nontreated controls (72% +/- 9% vs
      47% +/- 15%). Islet viability as measured using membrane integrity assays was
      similar in both the control (98% +/- 2%) and the A1AT-treated groups (99% +/-
      1%). EM results revealed a reduction or absence of secretory granules after
      exposure to proteases (TCE). CONCLUSION: Culture of impure human islet fractions
      in the presence of A1AT prevented insulin cleavage and improved islet recovery.
      A1AT supplementation of islet culture media, therefore, may increase the
      proportion of human islet products that meet release criteria for
      transplantation.

PMID- 20692407
TI  - Inhibition of inflammatory cytokine-induced response in human islet cells by
      withaferin A.
AB  - BACKGROUND: After islet cell transplantation, a substantial mass of islets are
      lost owing to nonspecific inflammatory reactions. Cytokine exposure before or
      after transplantation can upregulate expression of proinflammatory genes via the
      nuclear factor-kappaB signaling pathway, eventually resulting in islet loss.
      OBJECTIVE: To test the effects of a naturally occurring nuclear factor-kappaB
      inhibitor, withaferin A, on regulation of inflammatory genes in human islets.
      METHODS: Human pancreatic islets were isolated using a modified Ricordi protocol.
      Purified islets were cultured for 2 days. The effect of withaferin A treatment on
      islet cell viability was examined using the fluorescein diacetate-propidium
      iodide dye exclusion test, and on function using a static glucose stimulation
      assay. Islet cells were treated with a cytokine mixture (50 U/mL of interleukin
      1beta, 1000 U/mL of tumor necrosis factor-alpha, and 1000 U/mL of interferon
      gamma) for 48 hours with or without withaferin A, 1 microg/mL. Treated islets
      were used for real-time polymerase chain reaction (PCR) array analysis for
      expression of inflammatory genes, and expression of other selected genes was
      analyzed using real-time PCR with single primers. RESULTS: Glucose stimulation
      and viability assays demonstrated that withaferin A was not toxic to islet cells.
      Of 84 inflammation-related genes examined using real-time PCR array analysis, 9
      were significantly upregulated by cytokine treatment compared with the control
      group. However, addition of withaferin A to the culture significantly inhibited
      expression of all genes. CONCLUSION: Withaferin A significantly inhibits the
      inflammatory response of islet cells with cytokine exposure.

PMID- 20692408
TI  - Excellence of suito index for assessing clinical outcome of islet
      transplantation.
AB  - BACKGROUND: Monitoring functional islet mass after transplantation is critical to
      follow patients. Previously we demonstrated that the average secretory unit of
      islet transplant objects (SUITO) index within 1 month was an excellent predictor
      of insulin-free status or reduction in insulin dose. In this study, we analyzed
      the usefulness of daily SUITO index to assess clinical outcomes. METHODS: Five
      patients underwent islet transplantation, including 3 who received 2
      transplantations and 2 who received a single graft. All 5 patients achieved
      insulin-free status with 3 remaining insulin free at the time of evaluation. We
      analyzed the daily relative insulin dose and SUITO index. The daily relative
      insulin dose was calculated as the total daily insulin dose/average pretransplant
      insulin dose. The SUITO index was calculated as [fasting C-peptide
      (ng/mL)]/[fasting blood glucose (mg/mL) - 63] x 1,500. The data analyzed based on
      time after islet transplantation were categorized as within or after 1 month.
      RESULTS: Within 1 month after islet transplantation, there was no correlation
      between the daily relative insulin dose and the daily SUITO index (P = .068; R = 
      0.33). After 1 month, the daily relative insulin dose and the daily SUITO index
      were strongly correlated (P < .0001; R = -0.70). When the cutoff value of the
      SUITO index was decided at 26 for insulin-free status, the positive predictive
      value was 84.1% and negative predictive value 89.4%. CONCLUSION: SUITO index was
      an excellent index to assess clinical outcomes beyond 1 month after islet
      transplantation.

PMID- 20692409
TI  - Secretory unit of islet transplant objects (SUITO) index can predict outcome of
      intravenous glucose tolerance test.
AB  - BACKGROUND: Simple monitoring of engrafted islet function is important for follow
      up of recipients after islet transplantation. We previously developed a simple
      assessment tool for islet graft function; the secretory unit of islet transplant
      objects (SUITO) index. The aim of this study was to clarify the relationship
      between the SUITO index and the outcomes of intravenous glucose tolerance tests
      (IVGTT). METHODS: Fifteen series of blood samples from 6 islet recipients were
      collected before 3, 5, 10, 20, and 30 minutes after injection of 0.5 g/kg 50%
      dextrose. The SUITO index was calculated using plasma C-peptide and glucose level
      at fasting baseline. Samples were divided into the following 3 groups; low-SUITO
      (SUITO index <10; n = 3); middle-SUITO (SUITO index > or =10 to <26; n = 4); and
      high-SUITO (SUITO index > or =26; n = 8). RESULTS: A threshold SUITO index of 26
      showed good sensitivity (85.7%) and specificity (75.0%) to predict a blood
      glucose level of >10 mmol/L at 30 minutes. Blood glucose levels in the low-SUITO
      group were significantly higher than among the other 2 groups at baseline and 10,
      20 and 30 minutes (P < .05). Glucose-level areas under the receiver-operating
      characteristic curve during IVGTT in the low-SUITO group were also significantly
      larger than among the other 2 groups (P < .05). CONCLUSION: The SUITO index,
      using only a fasting blood sample, predicted IVGTT outcomes.

PMID- 20692410
TI  - Pancreata from pediatric donors restore insulin independence in adult insulin
      dependent diabetes mellitus recipients.
AB  - CONTEXT: The use of pediatric donors can increase the number of donors available
      for pancreas transplantation. AIM: The aim of this study was to verify if
      pancreas transplantation from pediatric donors is as effective as transplantation
      from adult donors to restore metabolic control in type 1 diabetic patients.
      MATERIALS AND METHODS: From 2000 to April 2009 we performed 17 pancreas
      transplantations from pediatric donors: 9 simultaneous kidney-pancreas (SPK), 6
      pancreas transplantation alone (PTA), and 2 pancreas after kidney (PAK). All
      subjects received whole organs with enteric diversion of exocrine secretions; 11
      underwent systemic and 6 underwent portal venous graft drainage. The
      immunosuppressive therapy was as follows: prednisone, mycophenolate mofetil, anti
      thymocyte globulin (ATG), and cyclosporine or tacrolimus. The pediatric donor
      population had a mean age of 15.3 years (range, 12-17), a mean weight of 60.1 kg
      (range, 42-75), and a mean body mass index (BMI) of 21 (range, 17.9-23.4).
      RESULTS: After 9 years the overall patient survival rate was 94.12%, whereas the
      graft survival rate was 63.35%. Normal glucose and insulin levels were maintained
      either fasting or during oral glucose tolerance test (OGTT). The group of
      recipients of pediatric organs was compared with patients receiving organs from
      adult donors (n = 125); the mean glucose values were lower in the pediatric
      group, whereas insulin production was higher in the adult patients. Early venous
      thrombosis was 17.6% in the pediatric group and 20% in adult recipients (Fisher
      exact test, P = not significant [NS]). CONCLUSION: Pediatric donors restored
      insulin independence in adult diabetic recipients, representing a valid source of
      organs for pancreas transplantation.

PMID- 20692411
TI  - Neurogenic differentiation 1 directs differentiation of cytokeratin 19-positive
      human pancreatic nonendocrine cells into insulin-producing cells.
AB  - BACKGROUND: It has been reported that the human pancreatic nonendocrine fraction,
      which remains after islet isolation, can be differentiated toward beta cells.
      However, the optimal method to accomplish this goal has not been established. In
      this study, we introduced the human neurogenic differentiation 1 (NeuroD1) gene
      into human nonendocrine pancreatic epithelial cells (NEPECs) and promoted insulin
      producing cells in vitro. METHODS: The human pancreatic nonislet fractions were
      obtained from brain-dead donors and cultured in suspension for 2-3 days followed
      by culture with G418 for 4 days. These cells (NEPECs) were then plated on dishes.
      The NEPECs spread into a cell monolayer within 7 days and all of the cells were
      cytokeratin-19 (CK19) positive. Seven days after plating, plasmids encoding human
      NeuroD1 gene under human CK19 promoter were transfected 3 times every other day
      (termed NEPEC+ND). Seven days after starting induction, these cells were
      characterized. RESULTS: Seven days after starting the induction of human NeuroD1,
      NEPEC+ND strongly expressed NeuroD1 and insulin mRNA. The ratio of NeuroD1
      positive cells in NEPEC+ND was significantly higher than in NEPEC. Human insulin
      positive cells in NEPEC+ND were also significantly greater than in NEPEC. Human
      insulin and C-peptide levels in culture medium in NEPEC+ND were significantly
      higher than in NEPEC. CONCLUSIONS: These findings demonstrated that human NeuroD1
      under control of the CK19 promoter can induce the differentiation of CK19
      positive NEPECs into insulin-producing cells.

PMID- 20692412
TI  - An acidic pH and activation of phosphoinositide 3-kinase stimulate
      differentiation of pancreatic progenitors into insulin-producing cells.
AB  - Adult pancreatic nonendocrine cells represent a potential alternative source of
      insulin-producing tissue for the treatment of diabetes. Differentiation of these
      cells is regulated by various signaling pathways including the phosphoinositide 3
      kinase (PI3K) pathway. Therefore, we evaluated the effect of PI3K on this
      process. Compared with untreated cells the differentiation of human nonendocrine
      pancreatic cells into insulin-producing elements was increased after treatment
      with IGF-1, EGF, and Exendin-4, growth factors known to be activators of the PI3K
      pathway (12.2 +/- 3.2% vs 9.1 +/- 3.2%). Treatment with PI3K pathway inhibitor
      wortmannin reduced the number of differentiated beta cells from 9.1 +/- 3.2 to
      0.7 +/- 0.4%. Reverse transcriptase polymerase chain reaction (RT-PCR) analysis
      revealed that insulin-like growth factor-1 (IGF-1), epidermal growth factor
      (EGF), and Exendin-4 significantly increased the expression of the transcription
      factor neurogenin-3, whereas the expressions of pancreatic and duodenal homeobox
      1 (PDX-1), neurogenic differentiation 1 (NeuroD) were increased only among
      samples treated with ZnCl2 and not significantly affected by treatment with the
      tested growth factors. Successful differentiation of IGF-1, EGF-, and Exendin-4
      treated cells into functional beta cells was confirmed by C-peptide secretion in
      response to 5 versus 20 mmol glucose stimulation (0.24 vs 0.91 pmol C
      peptide/microg DNA). These results showed that activation of the PI3K signaling
      pathway might be used to stimulate the differentiation of nonendocrine pancreatic
      cells into insulin-producing elements.

PMID- 20692413
TI  - Induction of insulin-producing cells from human pancreatic progenitor cells.
AB  - INTRODUCTION: We previously established a mouse pancreatic stem cell line without
      genetic manipulation. In this study, we sought to identify and isolate human
      pancreatic stem/progenitor cells. We also tested whether growth factors and
      protein transduction of pancreatic and duodenal homeobox factor-1 (PDX-1) and
      BETA2/NeuroD into human pancreatic stem/progenitor cells induced insulin or
      pancreas-related gene expressions. MATERIALS AND METHOD: Human pancreata from
      brain-dead donors were used for islet isolation with the standard Ricordi
      technique modified by the Edmonton protocol. The cells from a duct-rich
      population were cultured in several media, based on those designed for mouse
      pancreatic or for human embryonic stem cells. To induce cell differentiation,
      cells were cultured for 2 weeks with exendin-4, nicotinamide, keratinocyte growth
      factor, PDX-1 protein, or BETA2/NeuroD protein. RESULTS: The cells in serum-free
      media showed morphologies similar to a mouse pancreatic stem cell line, while the
      cells in the medium for human embryonic stem cells formed fibroblast-like
      morphologies. The nucleus/cytoplasm ratios of the cells in each culture medium
      decreased during the culture. The cells stopped dividing after 30 days,
      suggesting that they had entered senescence. The cells treated with induction
      medium differentiated into insulin-producing cells, expressing pancreas-related
      genes. CONCLUSION: Duplications of cells from a duct-rich population were
      limited. Induction therapy with several growth factors and transduction proteins
      might provide a potential new strategy for induction of transplantable insulin
      producing cells.

PMID- 20692414
TI  - Comparison of fresh and cultured islets from human and porcine pancreata.
AB  - INTRODUCTION: For clinical islet transplantation, many centers have recently
      introduced of human islet cultures prior to transplantation. They provide
      flexibility to evaluate isolated islets and pretreat patients. However, isolated
      islets deteriorate rapidly in culture. In the present study, we compared fresh
      human and porcine islets with cultured islets for c-Jun NH(2)-terminal kinase
      (JNK) activity. MATERIALS AND METHODS: Islet isolations from human and porcine
      pancreata were performed using the standard Ricordi technique with a modified
      Edmonton protocol. Isolated islets cultured for 24 hours at 37 degrees C with 5%
      CO(2) in culture medium were evaluated for counts and JNK activity. RESULTS:
      After 24 hours of culture, the percentages of surviving islets were 86.9% for
      human and 47.3% for porcine sources. JNK activity in isolated islets declined to
      a low baseline level after 24-hour culture. CONCLUSION: Both human and porcine
      islets deteriorated rapidly in 24-hour cultures, although the in vitro conditions
      did not induce JNK activation.

PMID- 20692415
TI  - Effects of pancreas transplantation on oxidative stress in pulmonary tissue from
      alloxan-induced diabetic rats.
AB  - PURPOSE: There is considerable evidence that cellular oxidative stress caused by
      hyperglycemia plays an important role in the genesis and evolution of chronic
      diabetic lesions. In this study, we determined the effectiveness of pancreas
      transplantation (PT) in preventing the imbalance caused by excessive production
      of reactive oxygen species over antioxidant defenses in lungs of rats rendered
      diabetic by alloxan injection. METHODS: Sixty inbred male Lewis rats, weighing
      250-280 g, were randomly assigned to 3 experimental groups: NC, 20 nondiabetic
      control rats; DC, 20 untreated diabetic control rats; and PT, 20 diabetic rats
      that received syngeneic PT from normal donor Lewis rats. Each group was further
      divided into 2 subgroups of 10 rats each which were killed after 4 and 12 weeks
      of follow-up. Plasma glucose, glycosylated hemoglobin, and insulin levels were
      determined in all rats. Lipid hydroperoxide (LPO) concentrations and enzyme
      activities of superoxide dismutase (SOD), catalase (CAT), and glutathione
      peroxidase (GSH-Px) were measured in the pulmonary tissue of all rats. RESULTS:
      The DC rats showed elevated blood glucose and glycosylated hemoglobin levels,
      with insulin blood levels significantly lower than the NC rats (P < .001). They
      also showed significantly increased LPO concentrations in the lungs (P < .01)
      after 4 and 12 weeks of follow-up. In contrast, SOD, CAT, and GSH-Px antioxidant
      activities were significantly reduced in these periods (P < .01) 12 weeks after
      diabetes induction. Successful PT corrected all clinical and metabolic changes in
      the diabetic rats, with sustained normoglycemia throughout the study. Excessive
      lung LPO production and low SOD, CAT, and GSH-Px antioxidant activities were
      already back to normal 4 weeks after PT. CONCLUSION: PT can control oxidative
      stress in pulmonary tissue of diabetic rats. It may be the basis for preventing
      chronic diabetic lesions in lungs.

PMID- 20692416
TI  - Pancreas transplantation prevents morphologic and ultrastructural changes in
      pulmonary parenchyma of alloxan-induced diabetic rats.
AB  - PURPOSE: The aim of this study was to evaluate whether pancreas transplantation
      (PT) is a suitable method for controlling histopathologic changes in lungs of
      alloxan-induced diabetic rats. METHODS: Sixty inbred male Lewis rats were
      randomly assigned to 3 experimental groups: NC, 20 nondiabetic control rats; DC,
      20 untreated diabetic control rats; and PT, 20 diabetic rats that received
      syngeneic PT from normal donor Lewis rats. Each group was further divided into 2
      subgroups of 10 rats each, which were killed after 4 and 12 weeks of follow-up.
      Clinical and laboratory parameters, fresh and fixed lung weights, and fixed lung
      volumes were recorded for all rats. Total number of alveoli, alveolar perimeter,
      alveolar surface area, and alveolar epithelial (AE) and endothelial capillary
      (EC) basal laminae thickening were randomly measured in 5 rats from each subgroup
      by using an image analyzer. For light microscopy, 250 alveoli were analyzed in
      each subgroup. For electron microscopy, 50 electron micrographs were examined for
      each subgroup. RESULTS: The DC rats showed elevated blood glucose and
      glycosylated hemoglobin levels, with insulin blood levels significantly lower
      than the NC rats (P < .001). Fresh and fixed lung weights and fixed volumes were
      significantly reduced in these rats, although their proportions to body weight
      were increased at 12 weeks (P < .01). The total number of alveoli in diabetic
      rats was higher than in control rats, whereas alveolar perimeter and surface area
      were significantly diminished (P < .01). AE and EC basal laminae were
      significantly thicker in DC than in NC (P < .01). Successful PT corrected all
      clinical and metabolic changes in diabetic rats, with sustained normoglycemia
      throughout the study. Morphologic and morphometric changes observed in diabetic
      lungs were completely prevented in PT rats from 4 weeks after transplant.
      CONCLUSION: We conclude that PT can control morphologic and ultrastructural
      changes in pulmonary parenchyma, suggesting a promising perspective for
      preventing other chronic diabetic lesions.

PMID- 20692417
TI  - Vascularization of artificial beds for pancreatic islet transplantation in a rat
      model.
AB  - An alternative prevascularized bed with a subcutaneously located entrance would
      substantially improve islet engraftment, requiring much less invasive surgery.
      Studies have described times necessary for the creation of an artificial pouch
      suitable for subsequent islet transplantation. Polymeric mesh shaped in rounded
      scaffolds were implanted both subcutaneously and into the major omentum of Brown
      Norway female rats (n = 7). The connective tissue together with vessels were
      embedded into scaffolds at 1 week without regard to site. In contrast to the
      major omentum, vessels within the subcutaneous connective tissue surrounding the
      devices started to decline in 2 weeks and almost disappeared 1 week later.
      Magnetic resonance imaging (MRI) detected changes in fibrous tissue surrounding
      the wall, but only large veins located beside the devices were visible using
      basic MRI. The blood supply to the internal surface of the created beds was
      important for islet engraftment, but information could be obtained only by using
      dynamic contrast-enhanced MRI.

PMID- 20692418
TI  - C5a-inhibitory peptide combined with gabexate mesilate prevents the instant blood
      mediated inflammatory reaction in a rat model of islet transplantation.
AB  - BACKGROUND: The instant blood-mediated inflammatory reaction (IBMIR), in which
      the activation of both the coagulation and the complement cascades plays a key
      role, is one of the main obstacles to successful islet transplantation. At
      present, however, no useful protocol is clinically available. Therefore the aim
      of this study was to examine whether complementary peptides against an active
      region of C5a were safe to suppress IBMIR, owing to their extremely low molecular
      mass, when combined with a clinically available anticoagulant. METHODS:
      Complement receptors on pancreatic tissues and isolated islets were analyzed by
      immunohistochemical staining and flow cytometry. Two-and-a-half islet equivalents
      per gram of syngeneic rat islet grafts were transplanted intraportally into 4
      groups of 10-13 animals each after streptozotocin induction of diabetes: control,
      gabexate (Gab), C5a-inhibitory peptide (C5aINH), and C5aINH plus Gab. Recipients
      injected with equivalent amounts of saline solution served as control subjects.
      Plasma samples were collected at 0, 0.5, 1, 3, 6, and 24 h after transplantation
      for analysis. We also evaluated the curative rate, intravenous glucose tolerance
      test, and insulin amounts in the liver of the recipients. RESULTS: C3a receptor
      (C3aR) was scarcely expressed on the isolated islets with relatively strong
      expression of C5a receptor (C5aR): C3aR: 0.44 +/- 0.38%; C5aR: 7.91 +/- 2.83%).
      However, C5aR was not expressed on pancreatic tissues before the isolation
      procedures. Thrombin-antithrombin complex was significantly suppressed in the 3
      treated groups (P = .0015). The curative rate was also significantly improved (0%
      vs 33% vs 67% vs 100%, respectively; P = .03). Glucose tolerance was
      significantly improved among the 3 treated groups (P < .0005). Insulin amounts in
      the liver were considerably higher among treated versus control hosts. Notably,
      the treatment did not affect the increased body weight of the recipient.
      CONCLUSIONS: This study suggested that C5a-inhibitory peptide combined with
      gabexate mesilate may be a useful approach to control the IBMIR induced in
      clinical islet transplantation and one that is free of side effects.

PMID- 20692419
TI  - Magnetic resonance imaging of transplanted mouse islets labeled with chitosan
      coated superparamagnetic iron oxide nanoparticles.
AB  - Although only 10% of islet recipients maintain insulin independence, 80% of them
      are C-peptide positive at 5 years after transplantation. To better understand the
      fate of transplanted islets, a magnetic resonance imaging (MRI) technique has
      been used to detect Feridex-labeled islet grafts in rodents. In this study, we
      used a novel MRI contrast agent, chitosan-coated superparamagnetic iron oxide
      (CSPIO) nanoparticles, to monitor mouse islet grafts. Male inbred C57BL/6 mice
      were used as donors and recipients of islet transplantation. The islet
      cytotoxicity was evaluated by fluorescein diacetate and propidium iodide staining
      for RAW cells incubated with CSPIO. After being incubated overnight with and
      without CSPIO (10 mg/mL), 300 islets were transplanted under the left kidney
      capsule of each mouse. After transplantation, 3.0-Tesla MRI of the recipients was
      performed biweekly until 19 weeks. At the end of study, the islet graft was
      removed for insulin and Prussian blue staining. The cell death rates in RAW cells
      did not increase with increasing CSPIO concentrations or incubation time. The
      grafts of CSPIO-labeled islets were visualized on MRI scans as distinct
      hypointense spots homogeneously located at the upper pole of left kidney. Their
      MRI signal was 30%-50% that of control islets and was maintained throughout the
      follow-up period. At 18 weeks, the histology of CSPIO-labeled islet graft
      revealed the insulin- and iron-stained areas to be almost identical. Our results
      indicate that isolated mouse islets labeled with CSPIO nanoparticles can be
      effectively and safely imaged by using MRI as long as 18 weeks after
      transplantation.

PMID- 20692420
TI  - Effect of triple costimulation blockade on islet allograft survival in sensitized
      mice.
AB  - BACKGROUND: Islet allograft rejection in sensitized recipients is difficult to
      control by costimulation blockade using anti-CD154 and cytotoxic T-lymphocyte
      antigen-4 immunoglobulin (CTLA4Ig). Because leukocyte function antigen (LFA) 1 is
      highly expressed on memory T cells, adding an LFA-1 blockade may inhibit memory T
      cell activities. We examined the effects on islet allograft survival of triple
      costimulation blockade in presensitized recipient mice. METHODS: C57BL/6 mice
      were sensitized by transplantation under the kidney capsule or intraperitoneal
      injection of Balb/c islets. Four weeks after transplantation, sensitization was
      confirmed by flow-cytometric detection of alloreactive antibodies. Diabetes was
      induced by a single intravenous injection of streptozotocin. Recipients were
      transplanted with 200 Balb/c islets under the right kidney capsule. Graft
      function was assessed by daily blood glucose and body weight records.
      Transplanted animals were divided into 3 treatment groups: group 1, control
      antibody; group 2, anti-CD154 and CTLA-4 Ig double therapy; group 3, anti-CD154,
      CTLA4Ig, and anti-LFA-1 triple therapy. Injections were administered every second
      day from day -2 to day 8. RESULTS: Naive mice rejected islet allografts between
      days 7 and 29 (mean 16 +/- 6 d; n = 5), sensitized mice in group 1 between days 0
      and 14 (mean 7 +/- 5 d; n = 8), in group 2 between days 4 and 16 (mean 8 +/- 4 d;
      n = 7), and in group 3 between days 4 and 26 (mean 11 +/- 7 d; n = 10).
      CONCLUSION: Triple costimulation blockade with anti-CD154, CTLA4Ig, and anti-LFA
      1 was not sufficient to improve islet allograft survival in sensitized
      recipients.

PMID- 20692421
TI  - Imaging of human islet vascularization using a dorsal window model.
AB  - BACKGROUND: The islets of Langerhans are micro-organs rich in blood vessels. The
      process of islet isolation and culture disrupts the vasculature of the islets.
      The reestablishment of an appropriate microvascular supply is an essential
      prerequisite for long-term survival and function of islet grafts. In this study,
      we examined the effects on the process of neovascularization of coating the
      islets with fibrin. METHODS: Isolated human islets were stained using the
      dioctadecylindocarbocyanine (DII) dye. An aliquot of the human islets were
      embedded in 3-dimensional fibrin. Human islets (100 islets-equivalents) were
      transplanted into a mouse dorsal window model to evaluate angiogenesis over 17
      days. Transplanted islets were divided into 2 groups: either free islets or
      islets coated with fibrin gel. Animals were imaged using intravital microscopy
      immediately and at 3, 4, 8, 11, and 17 days after surgery. The DII dye caused the
      islets to be fluorescent and visible using a rhodamine filter. Fluorescein
      isothiocyanate dextran was used to visualize vasculature structures surrounding
      the islets. RESULTS: Human islets coated with fibrin demonstrated an early
      appearance of a network of immature blood vessels that produced a significantly
      higher density/unit area for neovascularization by day 8 after transplantation.
      CONCLUSION: Our preliminary data showed that fibrin played a role in early
      neovascularization and support to sustain development of new blood vessels.
      Fibrin formed a matrix that helped to maintain the 3-dimensional structure of,
      and therefore reducing the environmental stress on islets.

PMID- 20692422
TI  - A survey of the attitudes of scientists toward xenotransplantation in Taiwan.
AB  - This study examined the attitudes of scientists in Taiwan's leading animal
      research institution toward xenotransplantation. The aim was primarily to
      evaluate the opinions of professionals in the biomedical field on key issues
      including ethical moral, legal, and regulatory issues raised by the
      biotechnology. A secondary objective was to identify potential factors that
      influenced opinions. A questionnaire-based survey was used to evaluate opinions.
      A test for internal consistency of the questionnaires to sample of 91 scientists
      was performed as well as a principal component analysis. We evaluated
      associations between variables using the nonparametric Kruskal-Wallis test. Among
      the subjects 85.2% thought that xenotransplantation can be more beneficial than
      harmful to human society and 94.3% believed that it is important to develop
      xenotransplantation. Also, 97.8% of participants believed that legislative
      guidelines should be adopted to regulate research in biotechnology. Gender was an
      influencing factor, whereas, variables such as religion, marital status, and age
      did not have obvious effects. Further studies on the general public are needed to
      detect other factors and to examine the attitude of nonprofessionals toward
      xenotransplantation.

PMID- 20692423
TI  - Some ethical aspects of xenotransplantation in light of the proposed European
      directive on the protection of animals used for scientific purposes.
AB  - Unlike what has happened in other times, society in general and especially the
      scientific community has become aware that animals share our sensitivity to pain
      and the capacity to suffer. In this regard, it is generally accepted that animals
      must be protected from all types of abuse. In fact, it is unavoidable today that
      animals used in scientific experiments enjoy the maximum degree of protection and
      well-being. This view is based on an ecocentric notion of living matter as
      opposed to the traditional anthropocentric approach because it has become evident
      that ethics should not be limited to those belonging to the same species.
      Likewise, there is a broad consensus-with the exception of members of certain
      animal protection groups-regarding the need to experiment with animals, when no
      alternative methods (AM) are available, given that the current state of
      scientific knowledge still does not allow for this type of experimentation to be
      entirely abolished. Nevertheless, we must keep in mind that not every scientific
      procedure in which animals are used is legitimate. On one side of the scale that
      symbolizes the legislation in this field, we find the weight of science and
      safety, and on the other side, the weight of ethics. In this article we have
      reviewed some of the main ethical criteria that serve as a basis to balance the
      scale, in other words, to guide and legalize animal experimentation in the field
      of xenotransplantation (XT). To that end, we take into account the current
      revisions made to the European Directive regarding the welfare of animals used in
      scientific procedures (86/609/EEC), in order to reflect, in turn, on the
      following issue: where is European institutional ethics headed on this issue?

PMID- 20692424
TI  - The attitude of Scottish citizens to xenotransplantation in the South East of
      Spain: an emerging population subgroup.
AB  - INTRODUCTION: It is important to discover whether xenotransplantation would be
      accepted in society. In populations where there are preclinical projects there is
      the possibility of xenotransplantation to humans. In the South East of Spain in
      recent years there has been a significant social change, due to the migratory
      influx, which is making it necessary to reconsider the level of acceptance of
      xenotransplantation. The objective of this study was to analyze the attitudes of
      and to determine relevant variables among the population from southeastern Spain
      who were born in Scotland. METHOD: A random sample of the population from the
      South East of Spain that was born in Scotland. (n = 350) answered a questionnaire
      with categories validated for our geographical area. The self-administered survey
      was completed anonymously between November 2005 and March 2006. The statistical
      analysis employed Student's t-test, the chi(2) test, and Fisher's exact test.
      RESULTS: The questionnaire completion rate was 93% (n = 325). Assuming the
      results were comparable with those obtained using human organs, most respondents
      (67%) favored xenotransplantation with 8% against and 25% undecided. With regard
      to xenotransplantation, if the results were worse than those achieved using human
      organs, 26% (n = 83) would be in favor, 55% (n = 178) undecided, and the
      remaining 19% (n = 62) against these procedures. The attitude was related to
      belonging to the male gender (P < .001), marital status (P = .008), level of
      education (P = .041), a partner's favorable attitude toward transplantation (P <
      .001), and a favorable attitude toward organ donation, either from a deceased (P
      = .001) or a living (P < .001) donor. CONCLUSION: The attitudes of Scottish
      residents in southeastern Spain were similar to those of the native Spanish
      population and determined by many psychosocial factors, mainly related to
      previous attitudes toward various types of human organ donation.

PMID- 20692425
TI  - Are veterinary students in favor of xenotransplantation? An opinion study in a
      Spanish university with a xenotransplantation program.
AB  - BACKGROUND: The shortage of available transplant organs has made it necessary to
      search for new alternatives, one of which is xenotransplantation. However, the
      use of animal organs and the personnel involved in its implementation could face
      opposition. Our objective was to analyze the attitudes of veterinary degree
      students in a Spanish university toward xenotransplantation and to determine the
      factors that affect its acceptance. METHODS: Of the 515 students registered in a
      veterinary degree course (2007-2008), we surveyed 482 94% of whom completed the
      questionnaire. Attitudes toward organ xenotransplantation were evaluated using a
      validated, self-administered questionnaire concerning organ donation, which was
      completed anonymously. We applied Student's t-tests and chi(2) tests. RESULTS: If
      xenotransplantation was confirmed as a clinical reality, 91% (n = 436) of those
      students surveyed would accept a xenotransplanted organ, whereas 9% (n = 46)
      would not. Furthermore, 95% (n = 457) would accept tissue xenotransplantation and
      97% (n = 467) cell xenotransplantation. Attitudes toward xenotransplantation were
      not affected by the academic year in which a student was studying, even when this
      was the year in which it was taught as a subject. Attitudes were not associated
      with any pyschosocial variable or attitude toward deceased organ donation; (P =
      .779). The students who believed that the demand for organs is not covered had a
      more favorable attitude toward xenotransplantation than those who think that
      there is no shortage (91% vs 70%; P = .027). CONCLUSION: Veterinary students had
      favorable attitudes toward xenotransplantation, assuming that the animal organs
      functioned as well as human organs. Therefore, these students could play
      important roles in the future promotion of this technique.

PMID- 20692426
TI  - Infection of porcine cells with human herpesviruses.
AB  - Porcine organs are valuable candidate materials for xenotransplantation to
      humans. Long-term maintenance of well functioning transplants is a prerequisite
      for success. Transplanted organs may be damaged by immune reactions or by
      infectious agents in hosts. Human herpesviruses (HHVs) establish life-long
      latency in humans after a primary infection. They can be reactivated with various
      stimuli, including immunosuppression. This study was performed to verify the
      infectivity of some HHVs toward porcine cells. PK-15 cells infected with HHV-1
      and HHV-2 showed cytopathology from 1 day after infection. Immunofluorescent (IF)
      staining of HHV-1- and HHV-2-infected PK-15 cells with respective antibodies
      demonstrated the expression of the respective viral antigens. Permissiveness of
      PK-15 to HHV-1 and -2 was confirmed by an infection test on Vero cells. Islet
      cells infected with HHV-5 showed no gross morphologic changes during the
      experimental course. A limited portion of islet cells reacted only to anti-IE1
      and anti-IE2, but not to anti-UL44 or anti-gB antibody by IF staining, whereas a
      small portion of endothelial cells reacted to anti-IEs and anti-UL44, but not to
      anti-gB antibody. HHV-1 and -2 can permissively infect porcine cells, but HHV-5
      infects a small proportion of cells with limited viral protein expression. HHV-4
      could not transform peripheral blood mononuclear cells from miniature pigs.
      Collectively, because some HHVs can infect and damage porcine cells or impair
      their functions, HHVs should be cautiously monitored and controlled in humans
      when porcine cells or organs are transplanted to human beings.

PMID- 20692427
TI  - The in vitro protection of human decay accelerating factor and hDAF/heme
      oxygenase-1 transgenes in porcine aortic endothelial cells against sera of
      Formosan macaques.
AB  - To mitigate hyperacute rejection, pigs have been generated with alpha-Gal
      transferase gene knockout and transgenic expression of human decay accelerating
      factor (hDAF), MCP, and CD59. Additionally, heme-oxygenase-1 (HO-1) has been
      suggested to defend endothelial cells. Sera (MS) (0%, 1%, 5%, 10%, and 15%) from
      Formosan macaques (Macaca cyclopis, MC), an Old World monkey wildly populated in
      Taiwan, was used to test the protective in vitro, effects of hDAF or hDAF/hHO-1
      on porcine aortic endothelial cells (pAEC) derived from hDAF(+), hDAF(+)/hHO
      1(+), and hDAF(+)/hHO-1(-) and 1 nontransgenic pAEC. Ten percent human serum (HS)
      served as a positive control. When MS addition increased to 10% or 15%, all
      transgenic pAEC exhibited a greater survival than nontransgenic pAEC. Noticeably,
      15% MS reduced survived to <10% versus >40% in nontransgenic and transgenic pAEC,
      respectively. These results revealed that hDAF exerted protective effects against
      MC complement activation. However, comparing with 10% MS and HS in pAEC of
      nontransgenic pigs, the survivability was higher in HS, suggesting that
      complement activation by MS was more toxic than that by HS. Furthermore,
      hDAF(+)/hHO-1(+) showed no further protection against effects of MS on transgenic
      pAEC.

PMID- 20692428
TI  - In vitro production of multigene transgenic blastocysts via sperm-mediated gene
      transfer allows rapid screening of constructs to be used in xenotransplantation
      experiments.
AB  - Multigene transgenic pigs would be of benefit for large animal models and in
      particular for xenotransplantation, where extensive genetic manipulation of donor
      pigs is required to make them suitable for organ grafting to humans. We have
      previously produced multitransgenic pigs via sperm-mediated gene transfer (SMGT)
      using integrative constructs expressing 3 different reporter genes. The aim of
      the present work was to evaluate the efficacy and safety of using 3 integrative
      constructs carrying 3 different human genes involved in the modulation of
      inflammatory responses. We developed an in vitro fertilization system to
      demonstrate that SMGT can be used to efficiently produce multigene transgenic
      embryos through a 1-step genetic modification using multiple integrative
      constructs each carrying a different human gene involved in the modulation of
      inflammatory processes (hHO1, hCD39, and hCD73). The results suggest that this
      system allowed an effective preliminary test of transgenesis optimization,
      greatly reducing the number of animals used in the experiments and fulfilling
      important ethical issues. We performed 5 in vitro fertilization experiments using
      sperm cells preincubated with all 3 integrative constructs. A total of 1,498
      oocytes were fertilized to obtain 775 embryos, among which 340 further developed
      into blastocysts. We did not observe any toxicity related to the transgenesis
      procedure that affected normal embryo development. We observed 68.5% transgenesis
      efficiency. Blastocysts were 48% single, 31% double, and 21% triple transgenic.

PMID- 20692429
TI  - ABO and RH1 blood group phenotyping in pigs (Sus scrofa) using microtyping cards.
AB  - Transplantation or transfusion with ABO disparity is a cause for rejection or for
      severe hemodynamic alterations. ABO groups in pigs are commonly an unknown
      variable, which has been previously assessed by means of hemagglutination tests
      or immunohistochemical procedures on tissues. Herein, we have reported a simple
      method using commercial microcards for human ABO typing. However, the reagents
      directly derived from human sera included in these cards can result in false
      determinations due to alpha-gal interference. The ABO groups of 19 wild-type pigs
      (Landrace x Large White) were assessed using 2 commercial cards: Human sera-based
      and monoclonal antibody-based cards. The human sera cards determined that 8 pigs
      belonged to the AB group and 11 to the B group. The monoclonal antibody cards
      determined that 8 pigs belonged to the A group and 11 to the O group. None of the
      pigs showed reactions to Rh1 antibodies. Because the B group has not been
      described in pigs, the reaction in human sera cards represented an interference
      with alpha-gal antigen, a molecule structurally similar to the B blood antigen.
      Thus, microtyping cards based on monoclonal antibodies provided simple, quick way
      to assess ABO groups in pigs used for xenotransplantation. ABO concordance should
      always be investigated for these types of procedures.

PMID- 20692430
TI  - Surgical and nonsurgical complications of a pig to baboon heterotopic heart
      transplantation model.
AB  - A modified immunosuppressive regimen, developed at the National Institutes of
      Health, has been employed in a large animal model of heterotopic cardiac
      xenotransplantation. Graft survival has been prolonged, but despite this, our
      recipients have succumbed to various surgical or nonsurgical complications.
      Herein, we have described different complications and management strategies. The
      most common complication was hypercoagulability (HC) after transplantation,
      causing thrombosis of both small and large vasculature, ultimately leading to
      graft loss. While managing this complication we discovered that there was a
      delicate balance between HC and consumptive coagulopathy (CC). CC encountered in
      some recipient baboons was not able to be reversed by stopping anticoagulation
      and administering multiple blood transfusions. Some complications had iatrogenic
      components. To monitor the animals, a solid state left ventricular telemetry
      probe was placed directly into the transplanted heart via the apex. Induction of
      hypocoagulable states by continuous heparin infusion led to uncontrollable intra
      abdominal bleeding in 1 baboon from this apical site. This occurrence
      necessitated securing the probe more tightly with multiple purse strings and 4
      quadrant pledgeted stay sutures. One instance of cardiac rupture originated from
      a lateral wall infarction site. Earlier studies have shown infections to be
      uniformly fatal in this transplant model. However, owing to the telemetry
      placement, infections were identified early by temperature spikes that were
      treated promptly with antibiotics. We had several cases of wound dehiscence due
      to recipients disrupting the suture line. These complications were promptly
      resolved by either re-approximating the wound or finding distractions for the
      baboon. A few of the most common problems we faced in our earlier experiments
      were related to the jacket, tether, and infusion pumps. It was difficult to keep
      the jackets on some baboons and the tether had to be modified several times
      before we assured long-term success. Infusion catheter replacement resulted in
      transplant heart venous obstruction and thrombosis from a right common femoral
      venous line. Homeostatic perturbations such as HC and CC and baboon-induced wound
      complications comprised most complications. Major bleeding and death due to
      telemetry implantation and infarct rupture occurred in 2 baboons. Despite the
      variety of complications, we achieved significant graft prolongation in this
      model.

PMID- 20692431
TI  - Left ventricular pressure measurement by telemetry is an effective means to
      evaluate transplanted heart function in experimental heterotopic cardiac
      xenotransplantation.
AB  - Evaluation of the function of heterotopic cardiac transplants has traditionally
      been accomplished by either manual palpation or serial biopsies. Both methods
      have drawbacks. Palpation can be difficult to differentiate a pulse from the
      graft versus a transmitted pulse from the native aorta. Serial biopsies, though
      accurate, require multiple laparotomies, leading to increased morbidity and
      possibly mortality rates. In this study we used an advanced telemetry system,
      consisting of an intra-abdominal implant, that was capable of continuously
      monitoring simultaneously several parameters of the transplanted heart and the
      status of the recipient. In a large animal model of heterotopic cardiac
      xenotransplantation (pig donor to baboon recipient), we implanted the device in
      12 animals: 8 with and 4 without immunosuppression. We monitored and continuously
      recorded the left ventricular pressure (both peak-systolic and end-diastolic
      [LVEDP]), heart rate, and the electrocardiogram pattern of the transplanted heart
      as well as the temperature of the recipient. The left ventricular pressure proved
      to be the most valuable parameter to assess graft heart function. In the 4
      nonimmunosuppressed cases, grafts were rejected acutely. In these cases, the end
      diastolic pressure increased sharply and the heart stopped contracting when the
      difference between the systolic and the diastolic pressure decreased to <10 mm
      Hg. The earliest reproducible sign of rejection was an increased LVEDP. Among
      long-term survivors, the increase in diastolic pressure was gradual, indicating
      progressive thickening of the myocardium and decreased compliance of the
      ventricle. Six of 8 immunosuppressed animals died of other complications before
      rejecting the transplanted heart. The telemetry was also helpful to indicate
      early onset of fever in the recipients, thus allowing us to intervene early and
      prevent potentially lethal septic complications. Continuous monitoring of several
      parameters via telemetry allowed detection of changes associated with rejection
      as well as other complications at an early stage, allowing prompt intervention,
      treatment, and possibly reversal of rejection.

PMID- 20692432
TI  - Super-high-dose islet transplantation is associated with high SUITO index and
      prolonged insulin independence: a case report.
AB  - INTRODUCTION: One of the current issues of clinical islet transplantation is the
      difficulty to achieve a prolonged insulin-free status. Functional islet mass
      gradually decreased after transplantation. We developed the SUITO index, which
      reflects engrafted islet mass. The SUITO (Secretory Unit of Islet Transplant
      Objects) index more than 26.0 is associated with an insulin-free status. In this
      study, we have experienced that super-high-dose islet transplantation maintained
      insulin-free status and a high SUITO index for a prolonged period. MATERIALS AND
      METHODS: Two islet isolations were performed in February 2007 and January 2008.
      Ductal injections were performed at the procurement site using the ET-Kyoto
      solution and pancreata preserved by a two-layer method. Islets were isolated
      using the modified Ricordi method. Both isolated islets were transplanted into a
      type 1 diabetic patient. Efficacy of islet transplantation was assessed by the
      amount of insulin requirements and SUITO index. RESULTS: Islet yields were
      514,467 islet equivalents (IE) and 872,174 IE, with purities of 49% and 85% for
      the first and second islet transplantations, respectively. The patient received a
      total of 24,327 IE/kg body weight. The immunosuppression was based on the
      Edmonton protocol. After the second islet transplantation, the average SUITO
      index for the following 1 month was 48.5, and the patient became insulin-free. At
      postoperative day 1006, the SUITO index was 44.6 and the patient maintained an
      insulin-free status with excellent glycemic control. CONCLUSION: Super-high-dose
      islet transplantation was associated with an high SUITO index and prolonged
      insulin independence.

PMID- 20692433
TI  - ET-Kyoto ductal injection and density-adjusted purification combined with potent
      anti-inflammatory strategy facilitated single-donor islet transplantation: case
      reports.
AB  - BACKGROUND: The necessity to use multiple donors for achieving insulin
      independence in clinical islet transplantation is still a major issue. We have
      developed a modified islet isolation method for non-heart-beating donors (Kyoto
      method) to significantly increase islet yield. In this study, we further modified
      the method for brain-dead donors and in addition, introduced a potent anti
      inflammatory strategy aiming for single-donor islet transplantation. MATERIALS
      AND METHODS: Two islet isolations used pancreatic ductal preservation with the
      modified Kyoto solution and a density-adjusted purification method. Anti
      interleukin-1-beta antibody (Anakinra) and anti-tumor necrosis factor-alpha
      (Eternacept) were administered during and after transplantation. The efficacy of
      the islet transplantation was assessed by the insulin requirement and SUITO
      (Secretory Unit of Islet Transplant Objects) index, wherein a value of more than
      26.0 seems to be associated with insulin independence. RESULTS: Both isolated
      islet preparations met the criteria for transplantation. They were transplanted
      into two type 1 diabetic patients, both of whom became insulin independent with
      stable glycemic control. The average SUITO index within 1 month was 29.2 and
      45.3. CONCLUSION: The islet isolation method combined with a potent anti
      inflammation strategy made it possible to achieve single-donor islet
      transplantation achieving a high SUITO index.

PMID- 20692434
TI  - Percutaneous embolization of periduodenal varix due to portal hypertension in a
      patient with kidney-pancreas transplantation: a case report.
AB  - Kidney-pancreas transplantation is a valid therapeutic option for patients with
      insulin-dependent diabetes mellitus. However, vascular complications associated
      with pancreas transplantation are not uncommon. Herein we have reported a 32-year
      old woman with a history of insulin-dependent diabetes mellitus and celiac
      disease. She underwent liver transplantation for acute hepatitis. After 7 years,
      the patient developed end-stage kidney disease beginning hemodialysis and being
      listed for a kidney-pancreas transplantation, which was successfully performed
      when she was 29 years old with enteric diversion (Roux intestinal loop
      reconstruction). Five years after kidney-pancreas transplantation, she was
      admitted to our hospital with serious intestinal bleeding and poor liver
      function. The ultrasound showed a pattern like a arteriovenous fistula near the
      head of the pancreas. Computed Tomography was not diagnostic; an arteriogram
      showed the presence of a mesenteric varix and a mesenteric-caval shunt through
      the duodenum of the pancreatic graft. The liver biopsy and portal pressure
      gradient showed portal hypertension and liver cirrhosis. To obtain time a waiting
      a new liver, the patient underwent percutaneous embolization of the mesenteric
      varix through jugular access. The procedure was uneventful. The patient was
      successfully transplanted 2 months later. Pancreas function was always
      satisfactory.

PMID- 20692435
TI  - First Congress of the Italian Society for Safety and Quality in Transplantation.
      Preface.

PMID- 20692436
TI  - The Italian Society for Safety and Quality in Transplantation (SISQT).
AB  - The Italian Society for Safety and Quality in Transplantation (La Societa
      Italiana per Ia Sicurezza e la Qualita nei Trapianti, SISQT) was founded in 2008
      to bring quality and safety issues at the center of donation and transplantation
      practice. In doing so, the SISQT seeks to involve, all health care professionals
      across the continuum of donation and transplantation, championing a
      collaborative, inclusive, inter-disciplinary, inter-professional, and multi
      stakeholder approach, in order to ease translation of the results of research
      into clinical practice. The program of the SISQT aims to (1) set a patient safety
      agenda with all professionals and stakeholders; (2) design and implement patient
      centered care processes and procedures; 3) help professionals harmonize and
      integrate operational practice with policy and regulatory mandates of the
      European union; (3) lay the scientific evidence on management of complex care
      across the continuum of donation and transplantation; (4) promote behaviors and
      cultural attributes in light of quality and safety. Accomplishment of these
      results requires cooperation of each care provider at all levels, from hospital
      to home to achieve integration of patient expectations within the scope of
      current transplant practice.

PMID- 20692437
TI  - Electrical safety during transplantation.
AB  - Technologic innovations enable management of medical equipment and power supply
      systems, with improvements that can affect the technical aspects, economics, and
      quality of medical service. Herein are outlined some technical guidelines,
      proposed by Istituto Superiore per la Prevenzione e la Sicurezza del Lavoro, for
      increasing the effectiveness of the power supply system and the safety of
      patients and surgeons in the operating room, with particular focus on
      transplantation. The dependence of diagnoses and therapies on operation of the
      electrical equipment can potentially cause great risk to patients. Moreover, it
      is possible that faulty electrical equipment could produce current that may flow
      through the patient. Because patients are particularly vulnerable when their
      natural protection is considerably decreased, as during transplantation or other
      surgery, power supply systems must operate with a high degree of reliability and
      quality to prevent risk, and must be designed to reduce hazards from direct and
      indirect contact. Reliability of the power supply system is closely related to
      the quality of the project, choice of materials, and management of the system
      (eg, quality and frequency of servicing). Among the proposed guidelines, other
      than normal referencing, are (1) adoption of a monitoring system to improve the
      quality of the electrical parameters in the operating room, (2) institution of
      emergency procedures for management of electrical faults, (3) a procedure for
      management of fires in the operating room, (4) and maintenance interventions and
      inspections of medical devices to maintain minimal requirements of safety and
      performance.

PMID- 20692438
TI  - National policies for risk management in Italy.
AB  - The Ministry of Health in Italy considers risk management (RM) to be one of the
      specific objectives to be developed by its national policies, as suggested by the
      European Union recommendations and by several international organizations, such
      as the World Health Organization (WHO), the Council of Europe, and the
      Organization for Economic Cooperation and Development. The National Health Plan
      stated the need to guarantee and monitor safety of health care and biomedical
      technology, with the development of a standardized computerized method to collect
      and analyze data on adverse events and with specific actions for education and
      training of all stakeholders, which is to be conducted at different levels of the
      health system governance, national, regional, and local. Over a 4-year period,
      the National Observatory for the Monitoring of Sentinel Events has collected data
      on 385 sentinel events, with a mortality rate of 54.8%. Compared with earlier
      reports, we have observed a reduction from 41% to 17% of sentinel events
      classified in the "nonspecified sentinel event" and an increase from 20% to 40%
      of cases in which an action plan has been developed. A manual for root cause
      analysis has been released with the aim of offering health operators an
      instrument to analyze the occurrence of an adverse event. Ten recommendations and
      a manual for safety in the operating room, which includes a checklist for safe
      surgery adapted on the basis of WHO suggestions, have been published. To date,
      eight guidelines for safety have been released to improve stakeholders'
      accountability. The Ministry of Health has also elaborated a program of specific
      actions to be developed over the next 2 years in several areas of RM. These
      initiatives confirm the strategic role of policies for RM in our country,
      allowing for a dynamic and proactive process, ensuring continuity of action and
      promoting a deep understanding of patient safety issues.

PMID- 20692439
TI  - Unintended transplantation of three organs from an HIV-positive donor: report of
      the analysis of an adverse event in a regional health care service in Italy.
AB  - In February 2007, three organs from an human immunodeficiency virus (HIV)
      positive donor were transplanted at two hospitals in the Tuscany Regional Health
      Care Service, owing to a chain of errors during the donation process. The heart
      beating donor was a 41-year-old woman who died as a result of head trauma. The
      patient's history did not highlight any risky behavior. The available data on
      previous hospital admissions reported a negative result on HIV testing. During
      the donation process, the result of the lab test performed for evaluation of
      organ suitability was mistakenly transcribed from positive to negative. This
      wrong negative result was then included in the donation record without any cross
      check. Therefore, the Regional Transplant Center allocated the liver and both
      kidneys. The patient also donated tissues, and a second laboratory conducted an
      evaluation of suitability for the tissue banks. During this process, only 5 days
      after the successful transplantation procedures, the positive HIV result was fed
      back to the Regional Transplant Center and the previous error discovered.
      Transplanted patients were immediately assessed and then treated with
      antiretroviral medications. A national commission soon performed a systems
      analysis of the adverse event. Besides the active error committed during the
      manual transcription for the HIV lab test result, the commission also identified
      technological factors, such as the lack of integration between the lab machine,
      the laboratory information system (LIS), and the donor record, as well as
      organizational factors, such as the distribution to two different labs of the
      suitability evaluation for organs and tissues. Recommendations included:
      automatic transmission of lab test results from the lab machine to the LIS and to
      the donor record, centralization of lab tests for suitability evaluation of
      organs and tissues, a training program to develop a proactive quality and safety
      culture in the regional network of donation and transplantations.

PMID- 20692440
TI  - Do "silent" brain deaths affect potential organ donation?
AB  - Brain death (BD) is not a stable, objective condition; in fact, it strongly
      depends on early intensive treatment before death, brain stem reflex testing, and
      intensive care unit (ICU) physician attitudes. Consequently, unpredictable
      "silent" BDs due to inadequate treatment or omitted declaration may affect
      potential organ donations. Several lines of evidence suggest that 55% to 65% of
      all deaths among patients with acute cerebral lesions (DACL) in the ICU may
      become brain deaths. Since DACL are easily measurable, deviations from the
      expected ratio of declarations will disclose "silent" BDs. Results from the
      National Registry of DACL in ICU settings have confirmed that BD declarations are
      consistently fewer than the number expected in Italy, particularly in regions
      where organ donation rates are low. Only 43% of the 10,304 referred DACL were
      potential donors in a 2-year period. Thus, around 1000 BDs per year are missing
      in Italy. Significant clinical factors for lost BDs may be older age and timing
      of death. As DACL represent the global donation potentiality (possible donors),
      we suggest the use of a new indicator-DACL in ICU per million population-and
      careful analyses of differences in DACL per million people among regions. In
      conclusion, since striking deviations from the expected ratio between BD
      declarations and deaths with an acute cerebral lesion exist in some regions,
      targeted training and support to ICUs should be planned. As adequate
      neurointensive treatment can improve outcomes and reduce "silent" BDs, more organ
      donors may exist where patients with acute cerebral lesion are better treated.

PMID- 20692441
TI  - Safety of bone marrow stem cell donation: a review.
AB  - Allogeneic hematopoietic stem cell transplantation (HSCT) represents the first
      choice of treatment or an important therapeutic option for several diseases, but
      it is still marked by morbidity and mortality. In contrast, the donation of
      hematopoietic stem cells (HSCs) is considered to be a safe procedure. The
      invaluable ethical source of donation and its central role in transplantation
      implies that the greatest attention be due to the donor and to the donation
      process through a serious monitoring protocol for donor safety. Both the Joint
      Accreditation Committee and the European Committee pay particular attention to
      the notification of adverse events and adverse reactions. Bone marrow donation is
      a well established procedure, that has now been performed for >30 years. Although
      it does not require drug administration, there is hospital admission for 1-3 days
      with 7-10 days off work. The main risk is related to the anesthesia. Pain in the
      aspiration area, together with astenia are considered to be the most frequent
      side effects, as shown by the USA National Marrow Donor Program experience in
      1,193 donations. In the European Group for Blood and Marrow Transplantation
      analysis performed between 1993 and 2005 on 27,770 first HSCTs from bone marrow,
      only 1 fatal event (pulmonary embolism) and 12 serious adverse events were
      observed. The most frequent adverse events were cardiac. The incidence of adverse
      events was significantly lower (P < .05) compared with peripheral blood HSC
      donors, which confirms the necessity of accurate attention to donor selection and
      evaluation in bone marrow donation.

PMID- 20692442
TI  - Efficiency of the tissue procurement process: what evaluation tools?
AB  - Evaluation of the efficiency of tissue procurement (TP) requires appropriate
      indicators. We report the results of a survey on all in-hospital deaths in
      Tuscany performed to identify potential indicators of efficiency with regard to
      donor identification and evaluation. In January 2004, we established a regional,
      compulsory, prospective program to monitor all in-hospital deaths in Tuscany.
      Currently, in Tuscany TP is performed if donors are < or =75 years without
      evidence of infectious or malignant diseases. Between January 2004 and December
      2008, we analyzed data on 75,921 in-hospital deaths, including 50,001 (66.9%) in
      subjects older than 75 years, while 25,920 (33.1%) were < or =75 years and thus
      considered for TP. Among the latter cohort, 11,657 (15.3%) presented with
      clinical contraindication(s), while 14,263 (18.8%) were fit for tissue donation.
      Of the latter population, tissue donation occurred in 3083 cases (ie, 4% of in
      hospital deaths or 11.8% of potential tissue donors). Contraindications to tissue
      donation were identified in 9861 cases (12.9%) based on clinical files, and in
      1796 (2.4%) after interview with the family. There was a great variability by
      regional hospital in the percent of contraindications identified after the family
      interview, from a low of 4% to a high of 45%. Based on our experience,
      implementation of efficiency parameters and improvement of the efficiency of the
      entire TP process requires compulsory reporting of in-hospital deaths by local
      transplant coordinators.

PMID- 20692443
TI  - Ensuring safety and quality of tissues in Italy: application of European
      directives.
AB  - Three European Directives published in 2004 and 2006 require Member States to
      take a series of regulatory actions to ensure appropriate quality and safety of
      tissues and cells. These directives define responsibilities to inspect and
      certify centers, to put vigilance systems in place and to publish information on
      certified centers and their activities. A European-funded project led by the
      Italian National Transplant Centre has supported Member States in the development
      of common guidelines for inspection, tools for vigilance, and training for
      inspectors. In Italy, inspections are conducted every 2 years at each tissue
      bank, and a vigilance system has been launched. Information on Italian centers
      and their activity is published in the Eurocet Registry.

PMID- 20692444
TI  - The role of nurses in the risk management of organ and tissue donation.
AB  - In the setting of organ and tissue procurement, lack of transplantation and the
      resulting missed opportunity for wait-listed patients might be considered as an
      untoward effect, since it results in longer wait-list times, higher mortality
      rates for potential candidates, and harm to the entire society. Beyond the
      classical definition holding that an adverse event is the inadvertent
      transmission of disease from a donor to a recipient, we advocate it should also
      include nonreporting of potential deceased donors; unsuccessful donor management;
      failure in organ/tissue procurement as the result of impossibility to assess
      brain death, lack of clinical data, or technical problems during surgical
      procedures. Based on their education, experience, and competencies, nurses share
      the responsibility to participate in the evaluation of risks and in the
      implementation of appropriate strategies for error prevention during the entire
      procurement process.

PMID- 20692445
TI  - Calcineurin inhibitors in renal transplantation still needed but in reduced
      doses: a review.
AB  - Despite their contribution in the success of organ transplantation, calcineurin
      inhibitors (CNIs) may be responsible for frequent and severe side effects that
      can affect graft survival and life expectancy. In this article, we have reviewed
      registry studies and randomized controlled trials (RCTs) that seek to avoid,
      withdraw, or minimize CNIs in renal transplant recipients. Attempts to completely
      avoid CNIs by administering mycophenolate mofetil (MMF) and/or sirolimus (SRL)
      have resulted in increased risks of rejection and side effects, with small
      advantage to improve renal graft function. Early withdrawal of CNIs after
      transplantation using administration of MMF can improve graft function but may be
      associated with a greater risk of acute or chronic rejection and graft failure.
      RCTs in which CNIs were replaced a few months after transplantation by SRL
      reported improved graft function among SRL-treated patients, but such a treatment
      was complicated by iatrogenic toxicity. Late replacement of CNIs with SRL did not
      produce a particular advantage and again was complicated by more frequent side
      effects. On the basis of these trials, it seems that CNI elimination can trigger
      rejection or side effects. Recent RCTs showed that minimization of CNI doses in
      association with everolimus does not increase the risk of rejection, allows one
      to obtain good graft function, and is well tolerated. Such an approach seems
      therefore preferable to complete elimination of CNIs with substitution of the
      current immunosuppressive drugs.

PMID- 20692446
TI  - Analysis of four scoring systems and monocentric experience to optimize criteria
      for marginal kidney transplantation.
AB  - There is a strong need among the transplantation community to identify common
      criteria to utilize the pool of expanded criteria donors (ECD), considering the
      disparity between organ demand and supply as well as the benefits of
      transplantation on long-term mortality compared with survival on dialysis, also
      in patients transplanted with these organs. The purpose of this article was to
      analyze scoring systems proposed in literature by Nyberg, Anglicheau, Rao (Kidney
      Donor Risk Index), and Schold, seeking to verify whether our clinical and
      histological allocation strategy matched the Nyberg score. Herein we have
      reported the results of a preliminary retrospective study on the 5-year outcomes
      of organs from 60 marginal donors, who were older than 50 years and
      histologically evaluated before implantation. The donors matched Nyberg class C
      and D, that is, marginal donors. We noted a tendency toward an association
      between global and vascular scores with class D (odds ratio 2.2 and 4.3,
      respectively). Kaplan-Meier graft survival curves were similar to Nyberg data:
      83% for class C versus 73% for class D at 5 years. Without any comparison to the
      Nyberg score, the only feature that was predictive of renal function at 5 years
      in our population was hypertension in the donor. Further studies are required to
      identify which of the scoring systems--clinical and/or histological--is more
      suitable to allocate ECD kidneys and to predict recipient outcomes.

PMID- 20692447
TI  - C4d-positive renal allograft rejection biopsies in cyclosporine-treated patients:
      single-center incidence and outcome.
AB  - T cell-mediated acute rejection (ATCMR) in renal transplant patients can have an
      antibody-mediated component. The aim of this study was to evaluate the incidence
      of renal biopsies showing ATCMR with C4d immunoreactivity and the correlation
      between C4d-positive ATCMRs and graft outcomes. We studied 216 renal transplant
      patients receiving cyclosporine-based immunosuppression (mean follow-up = 203.5
      +/- 42.5 months). Of these, 79 experienced biopsy-proven ATCMR (group 1), whereas
      137 did not show clinical or laboratory evidence of ATCMR (group 2). Mean serum
      creatinine levels were evaluated at 6 months, as well as 2 and 5 years after
      transplantation. The number of graft losses due to interstitial fibrosis and
      tubular atrophy (IF/TA) was greater in group 1 than in group 2 (P < .001 and P <
      .02, respectively), while graft survival was lower (P < .03). Staining with anti
      C4d antibody was performed in 61/77 type I ATCMR biopsies: seven cases showed
      diffuse C4d positivity with CD68(+) monocytes in peritubular capillaries observed
      in all cases. Three cases showed focal C4d positivity. Two ATCMRs were steroid,
      resistant. Graft loss due to IF/TA occurred in 4/7 patients (57.1%) who had
      previously experienced ATCMRs with diffuse C4d positivity; whereas it occurred in
      5/51 patients (9.8%) with previous C4d negative ATCMRs (P < .001). Patients with
      focal C4d positivity did not undergo graft loss due to IF/TA. In conclusion, at
      our center the diffuse C4d positivity that occurred in 11.4% of type I ATCMRs was
      associated with a poor prognosis.

PMID- 20692448
TI  - Kidney graft survival rates do not improve by era: the impact of the age factor.
AB  - We performed this study to evaluate whether older ages of donors and recipients
      negatively affected long-term graft survival. We compared 5-year graft survival
      rates of 89 recipients transplanted between 1991 and 1995 (period A) versus 221
      recipients transplanted between 1996 and 2000 (period B). Acute rejection rates
      and the number of donors and recipients >50 years of age were compared in the two
      periods. The 5-year graft survival rate in period B was 76.3% versus 82% in
      period A. In period B, the acute rejection incidence was 18% versus 40% in period
      A (P < .001). The overall 5-year graft survival was 86.2% for donors aged 21-50
      years and 65.7% for donor's aged >50 years (P < .0001) in period A versus 84.1%
      and 68%, respectively, in period B (P = .0023). In period A, 23.6% of donors and
      35.9% of recipients were >50 years old, versus 50.2% and 42.9%, respectively, in
      period B. The graft survival rate in period B was worse than in period A,
      although the acute rejection rate was lower. The older age of both donors and
      recipients in period B seemed to be an important cause of worse outcomes.

PMID- 20692449
TI  - Fibrosis progression and the pros and cons of antiviral therapy for hepatitis C
      virus recurrence after liver transplantation: a review.
AB  - The progression of fibrosis due to hepatitis C virus (HCV) recurrence after liver
      transplantation (OLT) is faster than in the pretransplant setting, leading to
      histologically documented cirrhosis within 5 years in 25% to 30% of cases.
      Whether it is associated with biliary complications or previous alcohol abuse,
      recurrent HCV is the main cause of graft failure and death after OLT. The most
      important donor risk factor for HCV recurrence is advanced donor age. The
      disease's course is even more aggressive if it is associated with anti-HCV
      positivity or graft steatosis. The type of calcineurin inhibitor does not seem to
      influence HCV recurrence. Avoiding or slowly tapering steroids has been
      associated with less disease recurrence, while steroid pulses to treat acute
      rejection episodes have been associated with a worse progression of fibrosis.
      Antiviral therapy (AT) is not always recommended in OLT patients, but is of some
      benefit. Fibrosis has been shown to ameliorate in sustained virological
      responders to AT and to progress significantly more in nonresponders. Using long
      term maintenance, AT has recently been shown to increase the probability of
      biochemical and histological responses, regardless of the timing of the HCV
      recurrence. In conclusion, the donor- recipient match should be assessed to limit
      HCV recurrences and their severity; AT is recommended to reduce or reverse the
      progression of fibrosis.

PMID- 20692450
TI  - Frozen-section diagnosis in donor livers: error rate estimation of steatosis
      degree.
AB  - A high degree of macrovesicular steatosis is associated with a significant risk
      of graft dysfunction. Most centers, including ours, consider 60% the limit value
      for transplantability, while others have adopted 30% as a cutoff. Pretransplant
      frozen-section (PFS) evaluation is used for reliable quantification of steatosis.
      However, the accuracy of PFS analysis for the degree of steatosis has largely
      been debated due to its high grade of variability and subjectivity. The aim of
      our study was to evaluate the accuracy of PFS diagnosis compared with subsequent
      paraffin histology samples. We retrospectively analyzed PFS from 52 consecutive
      liver donors. All PFS were blindly reviewed by two pathologists. The results were
      graded according to two classifications: (A) lower or higher than 60% steatosis,
      or (B) mild (0%-30%), moderate (30%-60%), or severe (>60%) steatosis. The rate of
      error for A (two-grade classification score) was 1.9% with the erroneous
      discharge of a viable organ. The error rate for B (three-grade classification
      score) was 7.7% with four discrepancies. In three cases, the discrepancy was
      related to the mild to moderate cutoff value, leading to a clinical error rate of
      5.8% (discharging organs with statosis >30%, when we used more strict criteria).
      Our study validated PFS analysis as a reliable technique when the maximum value
      for organ transplantation was 60% steatosis. There was a higher error rate when a
      cutoff value of 30% was used. This finding suggests the usefulness of another
      technique to support a more precise steatosis evaluation.

PMID- 20692451
TI  - Liver transplant quality and safety plan in anesthesia and intensive care
      medicine.
AB  - Patients scheduled for orthotopic liver transplantation (OLT) may have coexisting
      diseases and more likely receive grafts of poorer quality than in the past.
      Perioperative mortality and morbidity are usually due to a combination of factors
      related to the patient, graft, surgery, anesthesia, and intensive care
      management. Anesthesia and intensive care are the areas with the highest
      frequency and severity of errors. Error and accident risks are always present in
      this context where a human component is unavoidable. The matter of medical errors
      is becoming noteworthy worldwide. Nevertheless, data concerning medical errors
      during OLT are not available in Italy. There are only hypothetical evaluations.
      The number of adverse events may be high, but so far no specific programs have
      been developed to increase patient safety. To improve patient safety, anesthesia
      and intensive care units must use a proactive approach dedicated to an OLT
      program. We have presented herein a prevention policy to detect errors before
      they happen through incident reporting, anonymous and voluntary reports of
      adverse events or near misses, operating room checklists (patient, drugs,
      devices, equipment), improved training, safer facilities, equipment function, and
      adequate drug supplies for an OLT program.

PMID- 20692452
TI  - Patient satisfaction among liver transplant recipients: single-center survey.
AB  - A single-center survey using a semistructured questionnaire was conducted in
      liver transplantation recipients at discharge after the primary surgery. The
      objectives of the study were to assess patient satisfaction and to identify
      critical points that negatively affected their perception of the quality of care
      received, and to derive information to enable improvement in current standards of
      care. The questionnaire included 5 sections about quality and 1 section for
      suggestions. Patients were asked to provide answers on a 5-item Likert scale.
      Areas assessed included quality of staff, organization, boarding, privacy, and
      transfer of care. Among 51 recipients, satisfaction was high (>50%) in all areas.
      Lower satisfaction scores were given for room services, diet, and background
      music. The most frequently reported area of dissatisfaction (12%) was lack of
      availability of in-hospital physical rehabilitation programs. Despite overall
      satisfaction with quality of care, recipients reported lack of appropriate
      physical rehabilitation programs in the early posttransplantation period.

PMID- 20692453
TI  - Transplantation of hematopoietic stem cells: role of national transplantation
      center.

PMID- 20692454
TI  - Human de-epidermized dermis as a stem cell carrier.
AB  - Recently several types of skin equivalents have been developed, consisting of
      differentiated keratinocytes cultured on various dermal substitutes. Different
      models of reconstructed human skin have been proposed, such as human and animal
      de-epidermized dermis, inert filters, collagen matrices, lyophilized collagen
      membranes populated with fibroblasts, and other models populated with melanocytes
      and/or Langerhans cells. These skin equivalents mimic native skin in vivo. They
      have provided information about dermal-epidermal interactions, cell-cell, and
      cell-matrix interactions; responses of dermal and epithelial cells to biological
      signals and pharmacological agents; as well as effects of drugs and growth
      factors on wound healing. Human allodermis from tissue banks has been used for
      clinical purposes, namely, as support for autologous keratinocyte cultures and as
      a potentially ideal scaffold for dermal replacement. This bioproduct is
      considered to be the most suitable clinical carrier for autologous fibroblasts
      and keratinocytes, as well as an useful experimental model to study angiogenesis
      and to stimulate vascularization in reconstructed human skin. Because it is human
      derived, it is in our opinion the safest of all available types of skin
      equivalent. Having epidermal and dermal structures, it can be used in one-stage
      grafting procedures for wound closure.

PMID- 20692455
TI  - A common polymorphism in the monocyte chemoattractant protein-1 (MCP-1) gene
      regulatory region influences MCP-1 expression and function of isolated human
      pancreatic islets.
AB  - BACKGROUND AND AIMS: Islet transplantation is an attractive approach to treat
      type 1 diabetic patients. However, suboptimal islet engraftment still represents
      an unsolved problem. It has been shown that human islets release monocyte
      chemoattractant protein-1 (MCP-1), one of the most powerful macrophage
      chemokines, which may impair the fate of the transplant. The aim of this study
      was to evaluate the presence and role of MCP-1 in isolated human islets,
      including genotyping for a common polymorphism. METHODS: Pancreatic islets were
      isolated by enzymatic digestion and gradient purification from 41 nondiabetic
      multiorgan donors. We measured MCP-1 mRNA expression by quantitative real- time
      reverse-transcriptase polymerization chain reaction, analyzed the MCP-1 single
      nucleotide polymorphism, -2518 G/A (SNP, rs 1024611) and evaluated glucose
      stimulated insulin release (IR; microU/islet/min). RESULTS: MCP-1 mRNA expression
      was found in all studied batches of islets. Overall, IR was significantly higher
      at 16.7 mmol/L than 3.3 mmol/L glucose. We observed a significant negative
      correlation between MCP-1 mRNA expression and stimulation index (SI). We found
      that MCP-1 mRNA expression was significantly higher in CC and CT compared with TT
      genotype groups. Finally, SI was significant lower in the CC with respect to the
      TT genotype group. CONCLUSIONS: These data show that MCP-1 gene expression
      regulated by the -2518 G/A polymorphism, is correlated with glucose-stimulated
      insulin release. The study of MCP-1 expression and genotype on isolated islets
      before transplantation may be useful to understand the inflammatory response
      after infusion of human islets into patients with type 1 diabetes mellitus.

PMID- 20692456
TI  - Functional and survival analysis of isolated human islets.
AB  - BACKGROUND AND AIMS: Pancreatic islet transplantation has become one of the
      potential treatments for type 1 diabetes. We evaluated functional and viability
      parameters of isolated islets in relation to donors clinical characteristics and
      preparation variables. METHODS: Islets were isolated from 70 nondiabetic
      multiorgan donors of overall age of 62.5 +/- 15.9 years. There were 41 men and 29
      women. Their mean body mass index (BMI) was 25.62 +/- 3.09 kg/m(2). We evaluated
      the islet number (IEQ/g pancreatic tissue) insulin release (IR; microU/islet/min)
      in response to 3.3 (g) or 16.7 (G) mmol/L glucose; calcium flux concentration
      (CFC); and islet cell viability. RESULTS: IEQ was 5249 +/- 1505, with 73.7 +/-
      14.96% viable islet cells. IR was 0.03 +/- 0.01 at g and 0.11 +/- 0.06 at G
      (stimulation index [S] = 3.24 +/- 1.96). CFC was 1.95 +/- 1.03 DeltaRFU. We
      observed positive correlations between viable cells and IR at g (R(2) = 0.260; P
      = .013), IR at G (R(2) = 0.165; P = .013), and CFC (R(2) = 0.175; P = .047). A
      positive correlation was documented between BMI and g (R(2) = 0.245; P = .016)
      and negative correlations between age with SI (R(2) = 0.188; P = .052) and cold
      ischemia time with IEQ (R(2) = 0.865; P = .0061). CONCLUSIONS: These results
      showed that quality control of isolated human pancreatic islets allowed
      assessment of beta-cell function and survival before transplantation, revealing
      several important variables.

PMID- 20692457
TI  - Risk analysis of hematopoietic stem cell transplant process: failure mode,
      effect, and criticality analysis and hazard analysis critical control point
      methods integration based on guidelines to good manufacturing practice for
      medicinal product ANNEX 20 (February 2008).
AB  - The collection and handling of hematopoietic stem cells (HSCs) must meet high
      quality requirements. An integrated Quality Risk Management can help to identify
      and contain potential risks related to HSC production. Risk analysis techniques
      allow one to "weigh" identified hazards, considering the seriousness of their
      effects, frequency, and detectability, seeking to prevent the most harmful
      hazards. The Hazard Analysis Critical Point, recognized as the most appropriate
      technique to identify risks associated with physical, chemical, and biological
      hazards for cellular products, consists of classifying finished product
      specifications and limits of acceptability, identifying all off-specifications,
      defining activities that can cause them, and finally establishing both a
      monitoring system for each Critical Control Point and corrective actions for
      deviations. The severity of possible effects on patients, as well as the
      occurrence and detectability of critical parameters, are measured on quantitative
      scales (Risk Priority Number [RPN]). Risk analysis was performed with this
      technique on manipulation process of HPC performed at our blood center. The data
      analysis showed that hazards with higher values of RPN with greater impact on the
      process are loss of dose and tracking; technical skills of operators and manual
      transcription of data were the most critical parameters. Problems related to
      operator skills are handled by defining targeted training programs, while other
      critical parameters can be mitigated with the use of continuous control systems.
      The blood center management software was completed by a labeling system with
      forms designed to be in compliance with standards in force and by starting
      implementation of a cryopreservation management module.

PMID- 20692458
TI  - Key role of staff competencies for patient and donor safety in a bone marrow
      transplantation unit: design and implementation of an accredited training and
      self-assessment program.
AB  - Human resources represent at the moment the most critical factor in an hospital
      setting characterized by a high rate of staff turnover. It is important to ensure
      a consistent level of expertise and knowledge of professionals who work in health
      care facilities to provide quality services and simultaneously support the
      implementation of strategies for patient safety. Unfortunately, the development
      of effective interventions for training newly added staff and self-evaluation of
      skills possessed by trained staff are closely related to understanding critical
      aspects of the organization. At the new Center for Bone Marrow Transplantation
      and Blood Transfusion Service in Meyer Hospital, during the last year, a group of
      professional nurses and technicians completed a specific plan to train new staff
      and, at the same time, a program of self-assessment of skills for experienced
      staff. The main purpose of this project was to promote skills development by
      newly added as well as experienced staff, to identify areas of weaknesses, and to
      correct them with training (organized by the hospital, departmental, or
      individual) designed to improve performance.

PMID- 20692459
TI  - Patient satisfaction with nursing staff in bone marrow transplantation and
      hematology units.
AB  - Several validated questionnaires for assessment of hospitalized patient
      satisfaction have been reported in the literature. Many have been designed
      specifically for patients with cancer. User satisfaction is one indicator of
      service quality and benefits. Thus, we conducted a small qualitative survey
      managed by nursing staff in our Bone Marrow Transplantation Unit and Acute
      Leukemia Unit, with the objectives of assessing patient satisfaction, determining
      critical existing problems, and developing required interventions. The sample was
      not probabilistic. A questionnaire was developed using the Delphi method in a
      pilot study with 30 patients. Analysis of the data suggested a good level of
      patient satisfaction with medical and nursing staffs (100%), but poor
      satisfaction with food (48%), services (38%), and amenities (31%). Limitations of
      the study were that the questionnaire was unvalidated and the sample was small.
      However, for the first time, patient satisfaction was directly measured at our
      hospital. Another qualitative study will be conducted after correction of the
      critical points that emerged during this initial study, in a larger sample of
      patients.

PMID- 20692460
TI  - Case report: HIV infection from a kidney transplant.
AB  - The transmission of human immunodeficiency virus (HIV) through transplantation of
      human tissues and organs is rare but not impossible. A 27-year-old Bulgarian
      woman received a kidney transplant from a cadaveric donor owing to chronic renal
      failure due to glomerulonephritis of unknown etiology. Five days after the
      donation, the tissues showed HIV-1 infection, so she was immediately initiated on
      highly active antiretroviral therapy (HAART) with lopinavir/ritonavir,
      zidovudine, enfuvirtide, and lamivudine. Subsequently, according to the genotypic
      test which revealed a complex resistance pattern of the HIV-1, we changed the
      regimen to darunavir/ritonavir, etravirine, lamivudine, and enfuvirtide. The HIV
      1 genome (550 UI/mL), which was detected at 5 days after transplantation, rapidly
      declined to undetectable levels at 3 weeks after HAART. The CD4+ T-cell nadir was
      432 cells/microL (40%) to 1,400 cells/microL after 2 years. The
      posttransplantation course was complicated by cytomegalovirus pneumonia. At 32
      months after transplantation, the patient had experienced hypertension with
      secondary retinopathy, bilateral cataracts, diabetes, hypothyroidism,
      osteoporosis with multiple vertebral fractures, a hip prosthesis, and a bone
      infarction of the femur. Major management problems had been related to steroid
      and HAART treatment side effects. Therapeutic interactions between the
      immunosuppressants and the antiretroviral drugs were complex for management,
      requiring frequent checks of drug levels and dose-adjustments. We finally
      obtained a stable clinical and viroimmunologic condition. The transmission of
      multiresistant strains of HIV from unknown patients requires complex
      multidisciplinary management.

PMID- 20692461
TI  - Case report: cystic fibrosis, lung transplantation, and the novel H1N1 flu.
AB  - The H1N1 pandemic flu is a significant risk factor for both patients with chronic
      disease who need organ transplantation and transplant recipients. This population
      needs special care regarding comorbidities and related complications. MB, a 38
      year-old Italian cystic fibrosis male patient with lung and pancreatic
      involvement, was referred to our division in July 2009 for fever-associated
      arthromyalgia, headache, and rhinitis. Lung transplantation had been performed in
      September 2005, and he was subsequently treated with immunosuppressive therapy:
      tacrolimus, everolimus, and prednisolone. In the past, chronic respiratory
      colonization with Pseudomonas aeruginosa and intermittent infection with
      Aspergillus flavus, chronic renal failure, hypertension, and diabetes mellitus
      complicated his clinical history. He started antiviral treatment with oseltamivir
      despite no travel history and no respiratory symptoms. H1N1 swab was positive.
      Three days later, the patient was admitted to the hospital for the persistence of
      fever and the onset of cough. Chest x-ray showed a left lower pneumonia, which
      was confirmed by computerized tomography. Broad-spectrum antibiotic therapy led
      to an improvement of the clinical condition. The patient was discharged 8 days
      later; a control swab was negative. This case report suggests some general
      considerations regarding solid organ recipients: 1) Flu-related complications
      require early treatment (both antiviral and antibiotic); 2) active microbiologic
      surveillance is important to prevent lethal infections (ie, invasive
      aspergillosis); 3) evaluation of immunosuppressant blood levels is necessary for
      drug-drug interactions. Active prevention is the best option for decreasing
      morbidity and mortality in the transplanted patient.

PMID- 20692462
TI  - Transplantation in Hungary--preface on the occasion of Transplantation
      Proceedings becoming the official journal of the Hungarian Transplantation
      Society.
AB  - The first, long-term successful kidney transplantation happened 37 years ago in
      Hungary. At the same time an organized renal program was initiated followed by
      transplantations of other solid organs. The authors remember previous milestone
      operations and the preceding events. In 1982, Hungary was the first country in
      the Eastern block to introduce cyclosporine. After the Iron Curtain fell new
      circumstances and possibilities opened for the transplant community also. Young
      transplant surgeons were sent to Western countries returning with new
      experiences. In 1992 the heart transplantation program started in Budapest. The
      Universities of Debrecen and Pecs joined Budapest and Szeged with renal
      transplant programs. In 1994, a new Department was initiated at Semmelweis
      University with an immediate increase of 50%. The next year a liver
      transplantation program was launched. Pancreas transplants were performed in 1998
      in Pecs, followed by Budapest. In 2003, a collaboration was initiated between
      Geneva and Budapest for islet transplantation and another with Vienna for lung
      transplantation. This article provides an overview of Hungarian transplant
      activities.

PMID- 20692463
TI  - Changes in pituitary adenylate cyclase-activating polypeptide following renal
      ischemia-reperfusion in rats.
AB  - PACAP (pituitary adenylate cyclase-activating polypeptide) occurs in two
      biologically active forms, with 38 and 37 amino acid residues (PACAP38 and
      PACAP27). In mammalian tissues, PACAP38 is the dominant form. Diverse effects
      have been described in the cardiovascular, respiratory, gastrointestinal, and
      urogenital systems. PACAP is known for its strong cytoprotective effects, which
      are present endogenously as well, as proven by knockout studies and results
      showing that PACAP is up-regulated following diverse injuries. Little is known
      about such effects in the kidney. We have previously shown that PACAP is
      protective in renal ischemia-reperfusion injury. Therefore, the aim of the
      present study was to investigate the changes of endogenous PACAP following 60
      minute renal ischemia using radioimmunoassay. Changes were observed within 24
      hours following renal vessel clamping. In the cortex, an acute decrease was
      followed by an increase on the intact side, and levels returned to original ones
      on the operated side. In the medulla, changes were only observed on the clamped
      side: a marked up-regulation was detected in PACAP38-like immunoreactivity within
      the first 24 hours. The present study showed that PACAP38- and PACAP27-like
      immunoreactivities sensitively react to renal ischemia-reperfusion, the
      physiological importance of which awaits further investigation.

PMID- 20692464
TI  - Examination of protective effect of ischemic postconditioning after small bowel
      autotransplantation.
AB  - Ischemia/reperfusion (I/R) injury is a serious condition that results from some
      surgical procedures, including intestinal transplantation. Ischemic
      postconditioning is defined as brief periods of reperfusion alternating with
      reocclusion applied during the early minutes after reperfusion. The objective of
      this study was to investigate the effect of ischemic postconditioning before
      small bowel autotransplantation. Total orthotopic intestinal autotransplantation
      was performed in 30 white domestic pigs. Grafts were stored in cold University of
      Wisconsin solution for 1, 3, or 6 hours. Duration of reperfusion was 3 hours in
      all grafts. Before reperfusion, the intestine was postconditioned via 3 cycles of
      ischemia for 30 seconds and reperfusion for 30 seconds (ischemic postconditioning
      protocol). Tissue from the small intestine was obtained after laparotomy (control
      group) and at the end of reperfusion periods. To monitor oxidative stress, tissue
      concentrations of malondialdehyde and reduced glutathione, and activity of
      superoxide dismutase were determined at spectrophotometry. Tissue damage on
      sections stained with hematoxylin- eosin was evaluated using a quantitative
      method (Scion Image software; Scion Corp, Frederick, Maryland). Our results
      demonstrated that ischemic postconditioning significantly decreased the
      reperfusion-ended lipid peroxidation value (mean +/- SEM, 142.0 +/- 7.1
      micromol/g vs 125.0 +/- 2.1 micromol/g; P < .05). Moreover, the capacity and
      activity of endogenous antioxidant protective systems (glutathione 789+/-8.0
      micromol/g vs 934 +/- 5.7 micromol/g, and superoxide dismutase 110 +/- 9 IU/g vs
      126 +/- 4 IU/g; P < .05) remained higher in the ischemic postconditioning groups
      compared with tissues without ischemic postconditioning. At quantitative
      analysis, tissue injury was increased by the duration of cold preservation. The
      greatest injury was observed in the mucosal and submucosal layers and in the
      depth of crypts after 6 hours of preservation. Ischemic postconditioning
      significantly decreased intestinal wall injury in each group (P < .05). It was
      concluded that ischemic postconditioning before reperfusion mitigated oxidative
      stress and histologic damage during small bowel autotransplantation.

PMID- 20692465
TI  - Comparison of intestinal cold preservation injury on pituitary adenylate cyclase
      activating polypeptide in knockout and wild-type mice.
AB  - Tissue injury caused by cold preservation remains a problem in small intestinal
      transplantation. Pituitary adenylate cyclase-activating polypeptide (PACAP) has a
      central role in intestinal physiology. The objective of the present study was to
      compare the effects of cold ischemia injury in PACAP-38 knockout and wild-type
      mice after cold storage of small bowel. Cold ischemia was produced using small
      bowel preservation in University of Wisconsin solution at 4 degrees C in 20 PACAP
      38 wild-type mice for 1, 3, and 6 hours (groups 1, 2, and 3, respectively) and 20
      PACAP-38 knockout mice for 1, 3, and 6 hours (groups 4, 5, and 6, respectively).
      Biopsy samples of small bowel were obtained after laparotomy (control) and at the
      end of preservation periods. To determine oxidative stress, malondialdehyde,
      reduced glutathione, and superoxide dismutase concentrations were measured.
      Tissue damage was assessed using a quantitative method on sections stained with
      hematoxylin-eosin. After 6 hours, tissue lipid peroxidation was increased
      significantly in PACAP-38 knockout mice (mean +/- SD, 153.04 +/- 7.2 micromol/g)
      compared with sham-operated mice (110.44 +/- 5.5 micromol/g) and wild-type mice
      (120.0 +/- 1.1 micromol/g) (P < .05). The capacity and activity of the endogenous
      antioxidant system decreased significantly after 3 and 6 hours of preservation
      (reduced glutathione, 808.7 +/- 5.2 micromol/g and 720.4 +/- 8.7 micromol/g; and
      superoxide dismutase, 125.1 +/- 1.4 IU/g and 103.3 +/- 1.9 IU/g vs 212.11 +/- 5.8
      IU/g; P < .05). Quantitative histologic analysis demonstrated destruction of
      mucosal and submucosal layers and crypts in knockout mice compared with wild-type
      mice. These processes depended on duration of cold preservation. These findings
      demonstrate that PACAP-38 has a key role in protection against intestinal cold
      preservation injury.

PMID- 20692466
TI  - Mice deficient in neuropeptide PACAP demonstrate increased sensitivity to in
      vitro kidney hypoxia.
AB  - One of the well-known effects of pituitary adenylate cyclase activating
      polypeptide (PACAP) is its neuroprotective and cytoprotective actions including
      renoprotective effects. Mice deficient in endogenous PACAP exhibit several
      behavioral, metabolic, and developmental alterations. Furthermore, PACAP
      deficient mice have larger infarct volume in a model of cerebral ischemia,
      delayed axonal regeneration, and increased cell death in cerebellar oxidative
      stress. We have previously demonstrated that PACAP-deficient mice have increased
      susceptibility to in vitro oxidative stress, which can be counteracted by
      exogenous PACAP treatment. These results demonstrate that endogenous PACAP has a
      protective role against various stressors. The objective of the present study was
      to investigate whether endogenous PACAP has a protective effect in the kidney
      against in vitro hypoxia. Kidney cell cultures were isolated from wild-type and
      PACAP-deficient mice, and cell viability was assessed after in vitro hypoxia
      induced using CoCl(2). The sensitivity of cells from PACAP-deficient mice was
      increased to hypoxia: both after 24 and 48 hours of exposure, cell viability was
      significantly reduced compared with that in control wild-type mice. These results
      show that endogenous PACAP protects against noxious stimuli in the kidney and
      that PACAP may act as a stress sensor in renal cells.

PMID- 20692467
TI  - Arterial stiffness in chronic renal failure and after renal transplantation.
AB  - Arterial stiffness is an independent cardiovascular risk factor, along with
      aging, hypertension, and cardiovascular disease. The augmentation index (AIx) and
      pulse wave velocity (PWV) are early markers of atherosclerotic vascular changes.
      Arteriography was used to determine systolic and diastolic blood pressure, pulse
      pressure (PP), AIx, and PWV in 82 male and 64 female renal transplant recipients
      (mean [SD] age, 45.3 [11.2] years). Cardiovascular risk was assessed using
      echocardiography and ultrasonography of the carotid arteries. The left
      ventricular wall thickness, ejection fraction, and stenosis of the carotid
      arteries were also measured. Fasting serum creatinine, cystatin C, homocysteine,
      C-reactive protein, immunoreactive parathyroid hormone, lipid, and calcium
      phosphorus concentrations were determined. The serum cystatin concentration was
      2.1 (0.2) mg/L, and the homocysteine concentration, 15.2 (2.6) micromol/L. After
      transplantation, body mass index, fat mass, and visceral fat area increased
      significantly (P < .01). The AIx was increased (AIx > or =10%) in 20% of men and
      37% of women, PWV was increased (>10 m/s) in 43% of men and 34% of women, and PP
      was pathologically high (>12 m/s) in 10% of men and 12% of women. The PWV was
      significantly related to age (r = 0.52) and ventricular wall thickness (r =
      0.46). Pulse pressure, BMI, and systolic and diastolic blood pressure correlated
      positively but modestly with PWV. There was a significant relationship between
      AIx80 and systolic (r = 0.42) and diastolic (r = 0.39) blood pressure and PP (r =
      0.33). The ejection fraction correlated negatively with PWV and AIx. There was a
      strong association between carotid artery stenosis, PWV, and AIx80. All patients
      with PWV greater than 10 m/s demonstrated carotid artery stenosis. In conclusion,
      arteriography is an objective, noninvasive, and convenient method for early
      diagnosis and follow-up of atherosclerosis.

PMID- 20692468
TI  - Insertion/Deletion polymorphism of Angiotensin-converting enzyme as a risk factor
      for chronic allograft nephropathy.
AB  - Angiotensin-converting enzyme (ACE) inhibitor therapy is widely used to treat
      chronic allograft nephropathy (CAN), which suggests a possible role of the renin
      angiotensin system in the pathologic mechanism of the disease. The objective of
      this study was to investigate the possible link between CAN and ACE. The ACE
      insertion/deletion polymorphism and the amount and activity of ACE were
      determined in cadaver kidney recipients with CAN (n = 38) or normal renal
      function (n = 34). The DD genotype was observed significantly more frequently in
      the CAN group compared with the group with normal renal function. Moreover, the
      DD genotype was associated with a higher serum ACE concentration and greater
      serum ACE activity, compared with II genotype homozygotes. The insertion/deletion
      polymorphism of ACE affects ACE expression and activity in serum, and, therefore,
      may have an important role in the pathogenesis of CAN. These findings suggest
      that determination of the ACE genotype may be useful in identifying patients at
      high risk. In particular, the DD genotype may be considered an indication for ACE
      inhibitor therapy.

PMID- 20692469
TI  - Heat shock protein polymorphism predisposes to urinary tract malformations and
      renal transplantation in children.
AB  - BACKGROUND: Anatomical malformations of the kidney and urinary tract account for
      17% of pediatric renal transplantation procedures. Heat shock proteins (HSPs) are
      molecular chaperones with a protective function that promotes cell survival.
      HSP72 is an endogenous ligand for toll-like receptor TLR4, thereby stimulating
      innate immunity. Both in adults and children, decreased expression of HSP70s is
      associated with a number of kidney diseases. OBJECTIVE: To assess the prevalence
      of HSPA1A G(190)C, HSPA1B A(1267)G, and TLR4 A(896)G polymorphisms in children
      who had undergone kidney transplantation. PATIENTS AND METHODS: Genotypes were
      analyzed using allele-specific polymerase chain reaction in 41 pediatric
      recipients. Allelic prevalence was related to reference values in 65 age- and sex
      matched healthy children. RESULTS: Clinical data did not reveal a difference
      between any of the groups. HSPA1B (1267)GG genotype and HSPA1B (1267)G allele
      were observed more frequently in the transplant recipients compared with the
      control group: AA vs AG: odds ratio [OR], 12.6; 95% confidence interval [CI],
      1.58-100.0; P = .004; AA vs GG: OR, 20.80; 95% CI, 2.32-187.00; P = .01; and A vs
      G: OR, 2.10; 95% CI, 1.19-3.07; P = .01. Furthermore, the prevalence of the
      HSPA1B (1267)GG genotype was greater in transplant recipients with vs without
      urinary tract malformations: AG vs GG: OR, 0.10; 95% CI, 0.09-0.48; P = .007. No
      differences were observed in the other studied polymorphisms. CONCLUSION: Our
      findings suggest an association between the carrier status of HSPA1B (1267)G with
      urinary tract malformations, leading to end-stage renal disease requiring kidney
      transplantation. This observation raises further questions about the clinical and
      therapeutic relevance of this polymorphism to pediatric nephrology.

PMID- 20692470
TI  - Results and complications after living related kidney transplantation in Hungary:
      30 years' experience.
AB  - The number of patients suffering from kidney disorders is increasing the need for
      kidney transplantation. Kidneys originating from living donors (LD) show
      substantially better results than those originating from cadaveric donors (CD).
      We performed 3000 kidney transplantations between November 1973 and December
      2007, including 154 from LD (5.13%). The early kidney function as measured by the
      delta creatinine clearance was significantly better among the LD group (P <
      .001). There was no significant difference in the immunologic data between the LD
      and the CD groups (P = .047). Four years after transplantation the glomerular
      filtration rate (GFR) and the serum creatinine level treated to be better among
      the LD group with tacrolimus versus cyclosporine immunosuppression (P = .089). In
      the LD group, the acute rejection rate was lower with tacrolimus- versus
      cyclosporine based immunosuppression (P = .014).

PMID- 20692471
TI  - Small difference in international normalized ratio may yield a significant impact
      on prioritizing patients listed for liver transplantation.
AB  - Priority for liver transplantation is currently based on the Model for End-stage
      Liver Disease (MELD) score. The aim of our study was to assess in detail the
      contribution of international normalized ratio (INR) differences for MELD scores
      because of interlaboratory variability. The samples from 92 cirrhotic patients
      were measured on different systems combining three coagulometers and three
      thromboplastin products to determine variations in INR and MELD score. The INR
      differences among the first four systems varied between 0 and 0.2, resulting in
      MELD differences of 0 to 2. The MELD scores of 92 patients changed only among 10
      possible integers so that normally 2 to 10 patients shared the same MELD value.
      In some cases, one MELD score difference resulted in a 10 superpositioning on the
      waiting list. Including one more system (mechanical vs optical) into our
      investigations achieved a five MELD difference. Supposing an extreme situation
      where one patient competes with his or her lowest, all the other with their
      highest possible score (and visa versa), the difference may be even 20 positions,
      overturning the complete waiting list. In conclusion substantial interlaboratory
      differences in MELD score have profound clinical consequences.

PMID- 20692472
TI  - Can a cutoff value for cystatin C in the operative setting be determined to
      predict kidney function after liver transplantation?
AB  - Correct assessment and follow-up of kidney function is essential in liver
      transplant recipients. Glomerular filtration rate (GFR) represents the functional
      capacity of the kidney. The GFR is generally determined on the basis of
      creatinine clearance using several methods. It has been suggested that cystatin C
      be used rather than GFR. Production of cystatin C is not dependent on the same
      factors as creatinine. It is filtered and completely metabolized in the
      glomeruli, and is not secreted by the kidney tubules. The objective of this study
      was to determine a preoperative cutoff value for cystatin C based on kidney
      function estimated after liver transplantation. At prefixed times before and
      after orthotopic liver transplantation (OLT), serum cystatin C and creatinine
      concentrations were measured, and GFR was calculated using the Cockroft-Gault
      equation. Patients were divided into 2 groups according to GFR on postoperative
      days 1 to 5. Group 1 (healthy recipients) included patients with post-OLT GFR
      greater than 70 mL/min; and group 2 (kidney-impaired recipients), post-OLT GFR
      less than 70 mL/min. Group 2 demonstrated greater risk of postoperative
      complications, abnormal postoperative creatinine concentrations and GFR values,
      and worse patient and graft survival. Based on the preoperative cystatin C
      concentration, postoperative kidney function can be assessed. The cutoff value
      for preoperative cystatin was determined using receiver operating characteristics
      analysis. When the preoperative cystatin C concentration exceeded 1.28 mg/L, the
      postoperative GFR was less than 70 mL/min in the first 5 days after OLT. These
      findings suggest that if the cystatin C concentration exceeds the cutoff point
      preoperatively, there will be deterioration of kidney function after OLT. Along
      with other researchers, we suggest that cystatin C is a sensitive marker of post
      OLT kidney function.

PMID- 20692473
TI  - Outcome of liver transplantation based on donor graft quality and recipient
      status.
AB  - BACKGROUND: Availability of suitable donor organs has always limited the number
      of liver transplantations performed. Use of marginal donor organs is an
      alternative to overcome organ shortage. OBJECTIVE: To analyze the effect of
      various combinations of donor organ quality and recipient status on the outcome
      of liver transplantation. MATERIALS AND METHODS: Data from 260 whole-liver
      transplantations performed between January 2003 and September 2009 were analyzed
      retrospectively. Study groups were established according to donor organ quality
      (marginal score 0-1 vs 2-5) and recipient status (Model for End-Stage Liver
      Disease [MELD] score <17 or >17). In patients at low risk, 102 received optimal
      grafts (good-to-good group [G/G], and 75 received marginal grafts (bad-to-good
      group [B/G]. In patients at high risk, 46 received optimal grafts (good-to-bad
      group [G/B], and 37 received marginal grafts (bad-to-bad group [B/B]. RESULTS: No
      differences were observed in cumulative patient and graft survival rates;
      however, total survival differed in the early period after transplantation, that
      is, within 1 year. There was a higher rate of overall postoperative complications
      including initial poor graft function, bleeding, infection, and kidney failure in
      group B/B compared with group G/B (25 of 37 patients [67.5%] vs 27 of 46 patients
      [59.0%]), group B/G (25 of 37 patients [68%] vs 39 of 75 patients [52%], and
      group G/G (25 of 37 patients [68%] vs 43 of 102 patients [42%]) (P = .04).
      Patients with a high MELD score (G/B and B/B) demonstrated increased risk of
      postoperative complications. Use of donor organs with marginal score of 2 or
      higher in patients with high MELD scores increased early patient mortality.
      CONCLUSION: In summary, patients with a high MELD score (G/B and B/B) are at an
      increased risk of post-OLT complications. In contrast, use of marginal grafts
      (B/G and B/B) increased the rate of hepatitis C virus recurrence and decreased
      the response rate to antiviral therapy. The combination of impaired donor grafts
      and recipients at high risk should be avoided.

PMID- 20692474
TI  - Incidence of nonmelanoma skin cancer after human organ transplantation: single
      center experience in Hungary.
AB  - There is increasing evidence that nonmelanoma skin cancers (NMSCs) are the most
      frequently observed tumors in transplant recipients. The incidence of
      posttransplantation NMSC was determined using our dermatologic screening program.
      Included in the study were 116 white adults (70 men and 46 women; median age,
      49.3 years) who had undergone kidney or combined kidney-pancreas transplantation,
      with follow-up from September 2008 to December 2009. All patients underwent a
      full skin examination for NMSC, and completed a standardized questionnaire.
      Screening resulted in detection of 16 NMSCs in 11 patients out of 116 (9.5%).
      Lesions were equally distributed by sex, and were detected at a median of 4.1
      years posttransplantation. Histologic analysis verified 13 basal cell carcinomas
      and 3 squamous cell carcinomas (ratio, 4:1). The incidence of NMSC was
      significantly greater in patients who received cyclosporine immunosuppression
      therapy (16 vs 1; P < .05), had experienced 2 or more painful sunburns before
      transplantation (10 vs 11), or worked outdoors (10 vs 11). These data indicate
      the relevance of skin cancer surveillance in transplant recipients. Our results
      correspond to international statistics except for the ratio of basal cell
      carcinoma to squamous cell carcinoma. Further studies are needed to elucidate the
      reasons for this difference.

PMID- 20692475
TI  - Changes in oxidative stress in patients screened for skin cancer after solid
      organ transplantation.
AB  - Transplant recipients are at high risk of nonmelanoma skin cancer (NMSC).
      Ultraviolet radiation can generate oxygen free radicals (OFRs), leading to
      oxidative stress and carcinogenesis, primarily during immunosuppression therapy.
      In the present study, changes in oxidative stress were examined in transplant
      recipients with and without NMSC. The study included 116 white adults who had
      undergone kidney or combined kidney-pancreas transplantation. Dermatologic follow
      up revealed 16 NMSCs (13.8%). To monitor oxidative stress, peripheral blood
      samples were used to measure malondialdehyde (MDA), reduced glutathione,
      sulfhydryl (-SH) groups, OFRs, and activity of myeloperoxidase, superoxide
      dismutase, and catalase. The mean (SD) plasma MDA concentration was significantly
      greater in patients without NMSC compared with healthy control individuals
      (0.48+/-0.05 nmol/mL; P < .05), whereas MDA concentration in hemolysate was
      slightly increased. In peripheral blood samples, the MDA concentration in both
      plasma (0.71+/-0.03 nmol/mL) and hemolysate (87.74+/-1.25 nmol/mL) was
      significantly increased in the NMSC group compared with the healthy control group
      (0.24+/-0.05 nmol/mL vs 75.87+/-2.8 nmol/mL; P < .05) or patients without NMSC
      (0.48+/-0.04 nmol/mL vs 79.62+/-2.77 nmol/mL; P < .05). The reduced glutathione
      concentration was significantly decreased in the -SH groups compared with the
      healthy control group (P < .05). Antioxidant activity of myeloperoxidase (0.78+/
      0.05 IU/mL) and catalase (1855.8+/-45.41 IU/mL) was significantly increased in
      the group without NMSC compared with the healthy control group (0.41+/-0.1 IU/mL
      vs 1642.07+/-82.96 IU/mL) and the NMSC group (0.93+/-0.03 IU/mL vs 2180.5+/-15.03
      IU/mL). The superoxide dismutase activity was decreased slightly but not
      significantly. Total production of OFRs was significantly greater in the NMSC
      group compared with the non-NMSC group or the healthy control group (P < .05).
      These findings suggest that an imbalance exists between pro-oxidant and
      antioxidant status in transplant recipients, with a significant difference in
      patients with vs without NMSC.

PMID- 20692476
TI  - Effect of tacrolimus on the excitatory synaptic transmission between the parallel
      fibers and pyramidal cells in the rat dorsal cochlear nucleus.
AB  - AIM: The immunosuppressive drug tacrolimus has several effects on the central
      nervous system. Besides its protective effect in hearing deficiencies, it is also
      considered to be able to cause tinnitus. In the present work, we attempted to
      describe its effects on a characteristic synapse of the auditory system that may
      be involved in the pathogenesis of tinnitus. METHODS/MATERIALS: Slices of the
      dorsal cochlear nucleus (200 microm thick) were prepared from 9- to 14-day-old
      Wistar rats. In response to stimulation targeting the superficial layer of the
      nucleus, we recorded excitatory postsynaptic currents (EPSCs) developing in the
      cell bodies of the pyramidal neurons using whole-cell voltage clamps. Inhibitory
      synaptic activity was inhibited by the application of bicuculline and strychnine.
      Short-term plasticity was investigated using high-frequency stimulation (50 Hz).
      Unambiguous identification of the investigated neurons was ensured by employing
      biocytin in the pipette solution, which allowed the confocal reconstruction of
      the cells after the functional measurements. A concentration of 1 micromol/L
      tacrolimus was applied extracellularly. RESULTS: Tacrolimus effectively and
      reversibly inhibited glutamatergic neurotransmission in the investigated synapse
      from -145 +/- 26 pA to -55 +/- 15 pA (n = 7; P = .00928). In contrast, EPSC
      amplitudes without failures were not significantly reduced (from -153 +/- 26 pA
      to -131 +/- 23 pA) in the presence of tacrolimus, but there were increased
      failure numbers of synaptic transmission. These data suggested that application
      of tacrolimus produced a combined pre- and postsynaptic inhibition. CONCLUSION:
      Tacrolimus affected short-term synaptic plasticity in the rat dorsal cochlear
      nucleus. It was also capable of inhibiting the glutamatergic neurotransmission.
      These effects suggested that tacrolimus may have neuroprotective effects in this
      structure.

PMID- 20692477
TI  - Significance and imaging of lumbar veins and early-branching arteries in planning
      living-donor laparoscopic nephrectomy: two case reports from 21 months'
      experience.
AB  - A key aspect in planning laparoscopic living-donor nephrectomy is mapping of
      vascular variations. Lumbar veins and early-branching renal arteries are of
      utmost importance. To date, 43 candidates including 18 men and 25 women aged 25
      to 67 years have been examined at our clinic using 16-section multidetector-row
      computed tomography angiography. Each examination was double-checked by an
      experienced radiologist. Of the 43 patients, 31 underwent surgery. In 29 of 31
      patients (93.5%), the anatomy observed during surgery was identical to that
      demonstrated on the preoperative computed tomography scan. In 1 of 2 patients, 2
      separate arteries were found at surgery, rather than the prognosticated early
      branching arteries. In this patient, conversion to open surgery was necessary. In
      the other patient, a lumbar vein running into a retroaortic renal vein was
      discovered. In this patient, a 6-mm length of the joint stem contained the wall
      of the aorta and the periaortic tissue; thus, technically they were of separate
      origins. Careful mapping of the anatomy helps to prevent unexpected operative
      complications that are difficult to manage. Correct interpretation of the data
      must always be based on agreement between the radiologist and the surgeon.

PMID- 20692478
TI  - Spontaneous pneumomediastinum after kidney transplantation: case report.
AB  - Spontaneous pneumomediastinum is a rare condition with nonspecific signs and
      symptoms. A 39-year-old underwent cadaver kidney transplantation. After an
      uncomplicated operation, progressive dyspnea of unknown origin developed.
      Findings at chest radiography suggested pneumomediastinum, which was confirmed at
      computed tomography. Esophageal or tracheal injury was ruled out. The rapidly
      developing atelectasis of the left lung necessitated urgent bronchoscopy, which
      revealed occlusion of the left main bronchus. After removal of the occluding
      mucus plug, the clinical symptoms immediately improved, and the spontaneous
      pneumomediastinum resolved within 3 days. Asymptomatic increase in airway
      secretions in patients receiving peritoneal dialysis may result in mucus plug
      formation during general anesthesia, which can cause spontaneous
      pneumomediastinum.

PMID- 20692479
TI  - Mitigation of cytokine storm by intraoperative use of renal replacement therapy
      during combined liver-kidney transplantation.
AB  - BACKGROUND: Combined liver-kidney transplantation (CLKT) is a widely used
      multiorgan transplantation with good graft survival rates. Previous studies have
      shown beneficial effects of renal replacement therapy in critically ill patients.
      This observation led us to use intraoperative continuous veno-venous
      hemofiltration (CVVH) during multiorgan transplantations. METHODS: We analyzed
      (CRP) inflammatory response parameters of tumor necrosis factor (TNF)alpha,
      interleukin(IL)-6, procalcitonin (PCT) and C-reactive protein (CRP) at various
      stages of the combined transplantations. RESULTS: All patients survived with well
      functioning grafts. Mean +/- SD follow-up was 32.8 +/- 14.2 months. During the
      whole operation we used intraoperative CVVH starting at the beginning and
      continuing in the intensive care unit (ICU) afterward (mean +/- SD, 11.2 +/- 8.4
      hours). Intraoperative TNFalpha, IL-6, CRP, and PCT were measured before surgery,
      during hepatectomy in the anhepatic phase, before and after liver reperfusion,
      exactly before kidney reperfusion, after kidney reperfusion, and upon arrival in
      the ICU. The wash-out of cytokines together with hemodynamic stability gave
      optimal circumstances for recovery of the transplanted organs. CONCLUSIONS: CVVH
      based therapy offered stable intraoperative parameters, prevention of fluid
      overload, correction of metabolic disturbances, and wash-out of cytokines, which
      gave optimal circumstances for recovery of transplanted organs.

PMID- 20692480
TI  - Smoking following renal transplantation in Hungary and its possible deleterious
      effect on renal graft function.
AB  - Smoking is a known risk factor for kidney damage and also influences graft
      function following renal transplantation. Because smoking habits following kidney
      transplantation are not systematically evaluated, we analyzed them in a single
      center in Hungary. The survey was conducted among 402 randomly selected kidney
      graft recipients. We assessed smoking-related questions as well as clinical
      kidney disease and transplantation data. Posttransplantation renal function was
      analyzed based on serum creatinine values at 1 month and at 3 years after
      transplantation. In our study 25% (n = 102) of patients continued to smoke after
      transplantation. Smokers who received grafts displayed a significantly younger
      age compared with nonsmokers (40.1 +/- 13.4 vs 47.1 +/- 12.7 years; P < .001)
      independent of underlying kidney disease. Posttransplantation kidney function in
      smokers did not differ at 1 month after engraftment, but was significantly
      impaired at 3 years as assessed based on serum creatinine levels: 138.9 +/- 42.4
      versus 128.4 +/- 48.5 micromol/L (P < .05). Decrease of renal function correlated
      with smoking intensity defined in pack-years (r(2) = 0.102; P < .05). Smoking is
      common following kidney transplantation in Hungary and might represent a risk
      factor for kidney damage following renal transplantation. Therefore, effective
      tobacco-dependence treatment is necessary in this patient population.

PMID- 20692481
TI  - Should a complex uropathy be a contraindication for renal transplantation in
      children?
AB  - BACKGROUND: Anatomic and functional disorders of the lower urinary tract
      represent up to 40% of the causes of renal failure in children. Several centers
      avoid renal transplantation in these patients because of the high risk of
      complications and lower graft survival. The aim of this work was to determine the
      frequency of urinary tract abnormalities (UTAs) among our pediatric series, and
      to compare the frequency of complications, function, and long-term graft survival
      among patients without versus with UTA. METHODS: This single-center,
      retrospective study compared outcomes between pediatric recipients with versus
      without UTA. We analyzed demographic features, etiology, pretransplant protocol,
      urinary tract rehabilitation, incidence of complications, rejection events, as
      well as graft function and survival. RESULTS: Among 328 pediatric cases performed
      between 1998 and 2008, we excluded nine patients due to incomplete medical
      records, analyzing 319 procedures in 312 patients. Sixty-seven patients (21%) had
      UTA. The average age, weight, and height at the time of grafting were
      significantly lower in the urologic group: 11.1 versus 12.6 years, 28.8 versus
      34.4 kg; 125.4 versus 138.4 cm, respectively. There were significantly higher
      frequencies of a transperitoneal approach and vena cavae and aortic anastomoses
      among patients with UTA (P < .001), posing a greater technical challenge in this
      population. No differences in creatinine levels were observed at 0.5, 1, 2, 5,
      and 10 years: 1.3 versus 1.6 at 5 years, and 1.4 versus 1.5 at 8 years. Urologic
      complications, including urinary tract infections (UTIs), occurred among 80.6% of
      patients with UTA versus 42.1% in the non-UTA group (P < .001). UTIs appeared
      predominantly in patients with UTA (62.7% vs 35.3%, P < .001), representing a 2.7
      fold risk compared with those children transplanted for other reasons. Rejection
      incidence was similar in both groups (49.8%). There was no significant difference
      in 5-y (89.8% vs 85%) or 10-year (83% vs 67%) graft survivals between the groups
      (P = .162). CONCLUSION: Our results demonstrated that with proper
      interdisciplinary care, graft and patient survivals of pediatric recipients with
      UTAs were not affected; therefore, these patients should not be rejected for
      transplantation.

PMID- 20692482
TI  - Renal grafts with multiple arteries: a relative contraindication for a renal
      transplant?
AB  - INTRODUCTION: Advances in surgical techniques had achieved good outcomes in renal
      transplantation. There has been controversy with respect to the impact of
      multiple arteries on the outcome of the renal transplantations. OBJECTIVES: The
      objectives of this study were to examine the renal function and incidence of
      complications among grafts with one versus two or more arteries. MATERIALS AND
      METHODS: We evaluated 86 patients with renal transplantations between January
      2006 and January 2008 as a retrospective comparative study. The patients were
      stratified according to the number of renal graft arteries: group 1 had one
      artery (n = 66); group 2, two or more arteries (n = 16). RESULTS: The warm
      ischemia time was shorter among group 1 compared with group 2 (P < .03). There
      were significant differences between the groups with respect to mean blood
      pressure at 1 year (P < .04). The kidney biopsies after 1-year follow-up did not
      show any difference. CONCLUSION: We considered that the presence of anatomic
      variations was not a contraindication for renal transplantation, but that it is
      necessary to continue our follow-up to determine the real impact of these
      variations on graft and patient survivals.

PMID- 20692483
TI  - Role of major histocompatibility complex and ethnicity in acute renal graft
      rejection.
AB  - BACKGROUND: The major histocompatibility complex (MHC) plays a main role in
      antigen presentation. Class I, II, and III genes form defined "blocks" of
      conserved DNA sequences (conserved extended haplotypes) that are useful to follow
      the ancestry of a population. Each variant encodes a specific peptide that
      determines a particular individual's immune response. In addition, differential
      expression of HLA antigens in certain physiological and pathological conditions
      may participate in the pathogenesis of allograft rejection versus tolerance.
      OBJECTIVES: The aim of this study was to determine whether the specific HLA
      ancestry was associated with acute renal graft rejection among the Mexican
      mestizo population. MATERIALS AND METHODS: We studied 544 Mexican mestizo renal
      donors and their respective recipients for their serologically determined HLA and
      based on antigens haplotype assignments. The acute rejection group was compared
      with the nonrejection group among donors and recipients, correspondingly.
      RESULTS: Frequent Mexican alleles were observed in this study. Moreover, HLA
      B*61/-DR*04, HLA-A*35/-DR*06 (Amerindian ancestry), HLA-A*68/-DR*01, HLA-A*28/
      B*65/-DR*01 (African ancestry), and HLA-A*33/-B*65 (Caucasian ancestry) in donors
      were associated with acute renal graft rejection episodes. CONCLUSION: Knowing
      the ancestry of a donor's HLA molecules may help to individualize
      immunosuppressive therapy for posttransplant surveillance, because they may be
      more membrane-exposed in parenchymal cells, making them more susceptible of being
      recognized by the recipient's immune system.

PMID- 20692484
TI  - Risk factors for Banff borderline acute rejection in protocol biopsies and effect
      on renal graft function.
AB  - INTRODUCTION: The interpretation and handling of Banff borderline acute rejection
      observed in protocol biopsies from patients with stable renal function continues
      to be controversial. Our objective was to identify the risk factors for
      borderline acute rejection on 1-year protocol biopsies and to evaluate their
      effect on renal graft function after 2 years' follow-up. METHODS: We included 82
      kidney transplant recipients (KTR), who underwent 1-year protocol biopsies with
      normal or stable graft function. All KTR had follow-up of at least 2 years
      posttransplantation. We formed three groups: (1) KTR with a normal biopsy, (2)
      KTR with borderline changes, and (3) KTR with interstitial fibrosis/tubular
      atrophy (IF/TA). We searched for risk factors related to borderline injury. The
      main outcome to evaluate was renal function at 1 month, at protocol biopsy, and 2
      years posttransplant. RESULTS: The 82 patients included in this study showed no
      differences in immunosuppression, gender, etiology of renal failure, or
      percentage of panel-reactive antibodies. The risk factors associated with
      borderline lesions were: at least one biopsy due to allograft dysfunction and
      acute rejection events during the first year posttransplant (P = .011 and P =
      .021, respectively). Increased serum creatinine and estimated glomerular
      filtration rate decline were greater among the borderline lesion than the normal
      group, but similar to patients with IF/TA. CONCLUSION: Renal function decline was
      greater among borderline and IF/TA groups. However, the sum of insults, and not
      only the borderline injury itself, produces greater declines in renal function
      with greater risk for graft loss.

PMID- 20692485
TI  - Long-term complications and survival of patients after orthotopic liver
      transplantation.
AB  - INTRODUCTION: The survival rates among patients after orthotopic liver
      transplantation (OLT) has increased to 83% and 75% at 1 and 5 years,
      respectively. However, these patients are at increased risk of long-term
      complications. OBJECTIVE: To identify long-term complications and survivals among
      patients after OLT. METHODS: From September 1999 to July 2009 we evaluated long
      term complications among 78 consecutive patients after OLT including 46 males.
      RESULTS: Complications de novo after OLT were metabolic (n = 38; 67%), infections
      (n = 13; 23%), recurrent liver disease (n = 12; 21%), osteopenia/osteoporosis (n
      = 10; 18%), acute/chronic rejection (n = 8; 14%), renal failure (n = 2; 4%) and
      Kaposi's sarcoma (n = 1). Their overall survival at 118 months was 55%.
      CONCLUSIONS: The most common long-term complications after OLT were metabolic,
      infections, and disease recurrence.

PMID- 20692486
TI  - Anesthetic risk factors associated with early mortality in pediatric liver
      transplantation.
AB  - INTRODUCTION: Early mortality in pediatric patients after liver transplantation
      (30 days) may be due to surgical and anesthetic perioperative factors. OBJECTIVE:
      To identify anesthetic risk factors associated with early mortality in pediatric
      patients who undergo liver transplantation (OLT). MATERIALS AND METHODS: This
      retrospective study of all patients who underwent a deceased or living donor
      liver transplantation evaluated demographic variables of age, weight, gender,
      degree of malnutrition, and etiology, as well as qualitative variables of
      anesthesia time, bleeding, massive transfusion, acid-base balance, electrolyte
      and metabolic disorders, as well as graft prereperfusion postreperfusion
      characteristics. Chi-square tests with corresponding odds ratio (OR) and 95%
      confidence intervals as well as Interactions were tested among significant
      variables using multivariate logistic regression models. P < or =.05 was
      considered significant. RESULTS: We performed 64 OLT among whom early death
      occurred in 20.3% (n = 13). There were deaths associated with malnutrition (84.6%
      vs 43.6%) in the control group (P < .01); massive bleeding, 76.9% (n = 10) versus
      25.8% in the control group (P < .05) including transfusions in 84.6% (n = 11)
      versus 43.6% in the control group (P < .03); preperfusion metabolic acidosis in
      84.6% (n = 11) versus 72.5% (n = 37; P < .05); posttransplant hyperglycemia in
      69.2% (n = 9) versus 23.5% (n = 12; P < .01); and postreperfusion hyperlactatemia
      in 92.3% (n = 12) versus 68.6% (n = 35; P < .045). CONCLUSION: Prereperfusion
      metabolic acidosis, postreperfusion hyperlactatemia, and hyperglycemia were
      significantly more prevalent among patients who died early. However, these
      factors were exacerbated by malnutrition, bleeding, and massive transfusions.
      Postreperfusion hypokalemia and hypernatremia showed high but not significant
      frequencies in both groups.

PMID- 20692487
TI  - Surgical technique in cadaveric donors for partial hand allotransplant in
      patients with rheumatoid arthritis.
AB  - For patients with severe hand deformities due to rheumatoid arthritis, we propose
      an allotransplantation of an osteomyotendinose structure (OMTS), preserving the
      recipient's skin and sensory nerves. Our objective was to develop the surgical
      technique in a 10 cadavers, five as donors and five as recipients. The donor's
      hand was 10% to 15% smaller than the recipient's. Dissections were performed by
      two surgical teams under magnification. In the donor, the OMTS was procured at
      the distal third of the forearm, maintaining the integrity of the arterial
      system, with its concomitant veins and motor branches of the median and ulnar
      nerves, leaving the skin envelope. In the recipient, the OMTS was removed, taking
      care to preserve the cutaneous cover with the digital arteries in continuity with
      the superficial palmar arch and radial and ulnar arteries. Also, the digital
      nerves were maintained in the skin flap, in continuity with the median and ulnar
      nerves. Their motor branches were divided after emergence from the main nerves.
      The superficial dorsal veins and radial nerve were kept adhered to the cutaneous
      cover. Then, the donor OMTS was placed within the recipient cutaneous flap; all
      the anatomic structures were repaired. The average surgical time was 780 minutes.
      Methylene blue was present in the digital arteries. There were no difficulties in
      the anatomic repair. The surgical technique is quite laborious, especially the
      dissection of the recipient interdigital spaces. Due to the requirement for
      arterial system integrity, the cutaneous flap must be viable. Also, the
      allotransplanted OMTS has all necessary conditions to obtain good tissue
      perfusion for subsequent function. Procurement without skin permits a greater
      opportunity to find donors, and greater social and personal acceptance by the
      recipient.

PMID- 20692488
TI  - Successful renal transplantation from a deceased donor with pesticide
      intoxication: a case report.
AB  - The number of individuals awaiting organ transplantation exceeds the number of
      organs. Patients who die from intoxication are rarely accepted as potential organ
      donors. Herein we have presented the results of kidney transplantations performed
      from a deceased 20-year-old female donor with suicidal ingestion of a pesticide
      (carbamate). The procured kidneys were successfully transplanted. Patients and
      grafts are doing well at 4 months following transplantation. There are few
      reports of successful transplantation of organs obtained from patients who die
      from various intoxications. Poisoned patients represent another pool of organ
      donors for transplantation services.

PMID- 20692489
TI  - Preface. Summary of content--TCS in the diagnosis of movement disorders.

PMID- 20692490
TI  - Introductory remarks on the history and current applications of TCS.

PMID- 20692491
TI  - Method and validity of transcranial sonography in movement disorders.
AB  - Transcranial sonography (TCS) of the brain parenchyma in patients with movement
      and other neurodegenerative disorders has developed with increasing dynamics
      during the past two decades. The specific advantages of TCS are the different
      visualization of brain structures compared to other neuroimaging methods due to
      the different physical imaging principle, high-resolution imaging of echogenic
      deep brain structures, on-time dynamic imaging with high resolution in time,
      relatively low costs of technical equipment, wide availability, short
      investigation time, noninvasivity, mobility and bedside availability, and little
      corruption by patients' movements. TCS proved sensitive and reliable in detecting
      disease-specific alterations of brainstem structures and basal ganglia in various
      movement disorders. Here, we give an overview on the technical requirements and
      recommendations on the standardized application of TCS of deep brain structures
      in movement disorders. We discuss methodological potentials and limitations of
      TCS, its validity, and future developments.

PMID- 20692492
TI  - Transcranial sonography--anatomy.
AB  - Transcranial B-Mode sonography (TCS) allows quick, reliable, and inexpensive
      depiction of a number of brain structures, which may help in the diagnosis and
      differentiation of various movement disorders. In the following sections the
      anatomical structures in three standardized TCS planes (Section I) and the
      methods of measurement and typical pathological findings in specific structures
      (Section II) will be described. For better orientation, TCS images are
      complemented by compatible MRI images.

PMID- 20692493
TI  - Transcranial sonography in relation to SPECT and MIBG.
AB  - Neuroimaging techniques have substantially progressed over the past several
      years. These developments have provided new information about the degenerative
      processes involved in Parkinson's disease (PD). Functional imaging approaches
      such as positron emission tomography (PET) and single photon emission
      computerized tomography (SPECT) have been successfully employed to detect
      dopaminergic dysfunction in PD, even in preclinical stages. Myocardial
      scintigraphy with (123)I-metaiodobenzylguanidine ((123)I-MIBG) has been used to
      assess cardiac sympathetic function, and recent studies have revealed that the
      cardiac uptake of MIBG is significantly reduced in patients with PD and Lewy body
      dementia. In addition, substantia nigra (SN) hyperechogenicity, detected with
      transcranial sonography (TCS), might provide a marker of susceptibility to PD. We
      briefly review data regarding the clinical significance of these functional
      imaging studies in the diagnosis of PD, and discuss the diagnostic potential of
      the combining TCS of the SN with other functional imaging tools.

PMID- 20692494
TI  - Diagnosis of Parkinson's disease--transcranial sonography in relation to MRI.
AB  - Displaying the echo pattern (echogenicity) of brain tissue transcranial
      sonography (TCS) may provide new and complementary information to other
      neuroimaging methods. In contrast to conventional magnetic resonance imaging
      (MRI), TCS is able to detect highly characteristic changes in signal brightness
      of the substantia nigra (SN) in patients with idiopathic Parkinson's disease. In
      this review, TCS findings are related to conventional and advanced high-field
      brain MRI findings. On the basis of the MRI findings, especially with T2
      relaxometry, the possible role of trace metals in the genesis of altered
      echogenicity on TCS of brain parenchyma, especially of the SN, are discussed.

PMID- 20692495
TI  - Early diagnosis of Parkinson's disease.
AB  - The accuracy of the clinical diagnosis of Parkinson's disease (PD) is still
      limited. Especially in the early stages, when cardinal symptoms are not
      conclusive, diagnosis can be delayed as structural neuroimaging methods such as
      CCT or MRI do not provide characteristic features that allow the diagnosis of
      this chronic neurodegenerative disorder. Functional neuroimaging using PET and
      SPECT techniques is helpful in patients with first signs of parkinsonism, but
      expensive and not broadly available. In this scenario, transcranial sonography
      (TCS) has proven to be helpful. Up to 90% of PD patients show hyperechogenicity
      of the substantia nigra (SN) on TCS. Already in the early stages of PD this
      echofeature is visible, allowing the differentiation of very mildly affected
      patients with idiopathic PD from healthy persons and from patients with atypical
      parkinsonism with high sensitivity and specificity. Additionally, specific
      ultrasound features for some forms of secondary parkinsonism can be detected by
      TCS, helping in the early identification, for example, of patients with Wilson's
      disease. Therefore, especially in the early diagnosis, TCS can be recommended as
      a supplementary tool to facilitate the diagnostic classification of patients with
      first signs of parkinsonism.

PMID- 20692496
TI  - Transcranial sonography in the premotor diagnosis of Parkinson's disease.
AB  - Substantia nigra hyperechogenicity (SN+) is a common finding in transcranial
      ultrasound studies of parkinsonian patients. However, this echofeature is also
      found in 10% of healthy controls and is here associated with PD risk factors such
      as male gender and positive family history for PD, as well as with putative
      premotor symptoms such as hyposmia, depression, sleep disturbances, and subtle
      neuropsychological and motor impairment. SN+ is hypothesized to indicate an
      increased risk to develop PD during lifetime. PET studies substantiate this
      hypothesis, given that SN+ controls showed reduced striatal [(18)Fluoro] Dopa
      uptake in PET studies. First results of longitudinal follow-up studies show a
      higher relative risk for future PD in SN+ asymptomatic individuals.

PMID- 20692497
TI  - Pathophysiology of transcranial sonography signal changes in the human substantia
      nigra.
AB  - The characteristic change in ultrasound signal seen in the substantia nigra in
      Parkinson's disease and related disorders is known as hyperechogenicity and is
      suggested to be a risk or state marker for these disorders. The underlying
      cellular basis of this change, however, is unknown. Imaging studies on
      Parkinson's disease patients, experimental studies on animal models, and human
      postmortem studies support the hypotheses that an alteration in regional iron
      and/or change in regional cell composition within the substantia nigra underlie
      this echo feature. Future quantitative postmortem studies incorporating cellular
      and metal analyses of the substantia nigra, in Parkinson's disease patients and
      healthy controls of known echogenic status during life, will be important to
      clarify the cellular basis of this change.

PMID- 20692498
TI  - Transcranial sonography for the discrimination of idiopathic Parkinson's disease
      from the atypical parkinsonian syndromes.
AB  - We reviewed eight studies on transcranial sonography (TCS) as a tool for
      differentiating idiopathic Parkinson's disease (IPD) from atypical parkinsonian
      syndromes (APS) and included some first data on TCS findings in the subforms of
      PSP. Changes of specific structures on TCS like the substantia nigra (SN),
      lenticular nucleus (LN), and the third ventricle are discussed as well as how
      they can contribute to differentiate between IPD, multiple system atrophy (MSA),
      progressive supranuclear palsy (PSP), Lewy body disease (LBD), and corticobasal
      degeneration (CBD). We finish with an algorithm that may be used to employ TCS as
      a diagnostic instrument delineating IPD from the APS and discerning among the APS
      themselves. As TCS is at present the most promising tool for this particular
      diagnostic problem, this algorithm might be a suitable hypothesis to study in
      future research.

PMID- 20692499
TI  - Transcranial sonography in the discrimination of Parkinson's disease versus
      vascular parkinsonism.
AB  - Cerebro-vascular disease is a well-known cause of parkinsonism. However, so far,
      there are no standardized clinical criteria that allow the diagnosis with
      accuracy and reliability. Rather, there is a great symptom overlap between
      idiopathic Parkinson's disease, other causes for parkinsonism, and vascular
      parkinsonism. Therefore, additional instruments are necessary to improve
      diagnostic accuracy. Transcranial sonography of brain parenchyma (TCS) has become
      a broadly applied tool in the diagnosis of Parkinson's disease, and secondary and
      atypical parkinsonian syndromes. In contrast to patients with idiopathic
      Parkinson's disease, patients with vascular parkinsonism in general show no
      hyperechogenicity of the substantia nigra. In contrast to a number of patients
      with atypical parkinsonian syndromes, also the basal ganglia are usually
      normoechogenic on TCS. A more specific approach to vascular parkinsonism includes
      the Doppler or duplex technique in order to show stenosis of vessels. Therefore,
      the combination of TCS and Doppler/duplex imaging might help to improve diagnosis
      of vascular parkinsonism transcranial.

PMID- 20692500
TI  - TCS in monogenic forms of Parkinson's disease.
AB  - During the last decade, mutations in a growing number of genes have been found to
      cause monogenic forms of Parkinson's disease (PD). Moreover, many studies shed
      light on their contribution to sporadic variants of PD. Since hyperechogenicity
      of the substantia nigra (SN) represents a characteristic hallmark of sporadic PD
      questions arise concerning the echo pattern of monogenic forms of this disorder
      on TCS.

PMID- 20692501
TI  - Transcranial sonography in brain disorders with trace metal accumulation.
AB  - Transcranial sonography (TCS) can detect trace metal accumulation in deep brain
      structures with higher sensitivity than conventional MRI. Especially, increased
      iron content in the substantia nigra in Parkinson's disease, increased copper
      content in the lenticular nucleus (LN) in Wilson's disease and idiopathic
      dystonia, and increased manganese content in the LN in manganese-induced
      Parkinsonism were detected with TCS, even in subjects with normal MRI. TCS,
      therefore, might be useful to detect an increased risk of developing neurological
      symptoms in relatives of patients with Parkinson's or Wilson's disease. The exact
      mechanism of how an elevated trace metal content leads to an increased
      echogenicity needs to be further elucidated.

PMID- 20692502
TI  - Transcranial sonography in dystonia.
AB  - The cause of idiopathic dystonia is not entirely elucidated. In the
      pathophysiological model of dystonia, the basal ganglia play a major role, mainly
      putamen, globus pallidus internus, thalamus, and cortex. However, using
      conventional structural neuroimaging methods, no specific alterations could be
      detected in this area. Using transcranial sonography (TCS) as a noninvasive, easy
      to perform, and side-effect-free method, it could be shown that in up to 75% of
      patients with cervical dystonia (CD), in a high percentage of other focal
      dystonias, but seldom in facial and genetically determined dystonia,
      hyperechogenicity of the medial part of the lentiform nuclei (LN) can be
      visualized in the third ventricular scanning plane. Based on these TCS findings
      an increased copper content of the LN could be verified in dystonia, opening new
      perspectives on possible pathophysiological aspects and future research. In
      clinical routine, this method may be used for early and differential diagnosis of
      primary dystonia.

PMID- 20692503
TI  - Transcranial sonography in essential tremor.
AB  - Essential tremor (ET) is the most common adult movement disorder. Especially in
      early stages the clinical differentiation between essential and Parkinsonian
      tremor may be a diagnostic challenge. Recent studies have consistently found
      hyperechogenic alterations in the area of the substantia nigra (SN) in patients
      with Parkinson's disease (PD) using transcranial sonography (TCS). The present
      chapter summarizes five studies, which have been performed to investigate SN
      echogenicity in patients with ET compared with PD patients and healthy control
      subjects and also includes our own experience. All of the studies published so
      far have shown that hyperechogenicity of the SN is a typical finding in about 90%
      of patients with PD, but not in patients with ET. In ET patients, the prevalence
      of hyperechogenicity is in the range of healthy control subjects or slightly
      above, which may indicate an increased risk for PD in the subgroup of ET patients
      with hyperechogenicity, consistent with the increased risk for PD that has been
      established in ET patient cohorts. As TCS is a noninvasive and inexpensive
      method, it seems to be a valuable instrument in the differentiation between ET
      and PD. Future follow-up studies on ET patients with SN hyperechogenicity will
      reveal whether those with increased echosignal are indeed the ones who may
      develop PD later in life.

PMID- 20692504
TI  - Transcranial sonography in restless legs syndrome.
AB  - Restless legs syndrome (RLS) is one of the most common neurological disorders.
      The diagnosis is mainly based on the patient's report of the characteristic
      symptoms and further on the response to dopaminergic treatment. In the past
      years, transcranial B-Mode sonography (TCS) of the mesencephalic brainstem has
      been introduced as a promising new method to assist the diagnostic approach to
      RLS. This review of literature describes the typical TCS findings in RLS
      including hypoechogenicity of the substantia nigra and raphe as well as
      hyperechogenicity of the red nucleus. The diagnostic parameters for patients with
      idiopathic and various forms of symptomatic RLS will be discussed as well as the
      current knowledge about the pathophysiology underlying these sonographical
      abnormalities.

PMID- 20692505
TI  - Transcranial sonography in ataxia.
AB  - Transcranial sonography (TCS) identifies basal ganglia alterations in
      extrapyramidal movement disorders such as Parkinson's disease or dystonia.
      Although only rarely reported, TCS also reveals signal alterations of basal
      ganglia in several forms of hereditary and nonhereditary ataxia. Here, the
      examination procedure and its diagnostic value for the classification of ataxia
      are reviewed. Three TCS studies reported hyperechogenicity of substantia nigra
      (SN) as a frequent finding in spinocerebellar ataxia type 2, type 3, and type 17,
      indicating a vulnerability of the nigrostriatal system in SCA patients. A new
      "cerebellar examination plane" was proposed, allowing better visualization of
      fourth ventricle enlargement and nucleus dentatus hyperechogenicity as a
      characteristic finding in SCA3 patients. In sporadic Creutzfeldt-Jakob disease, a
      blurry inhomogeneous hyperechogenic signal pattern of lentiform nucleus was
      identified in all of the patients in a small case series. Furthermore, distinct
      bilateral hyperechogenicity of pallidostriatal regions have been described as a
      novel diagnostic feature in the sonographic differentiation of extrapyramidal and
      atactic movement disorders. TCS is a commonly available, noninvasive, and
      inexpensive diagnostic tool, which provides reliable information about the
      morphology of the brain in ataxias, even in agitated patients who do not tolerate
      other imaging techniques. Further neuropathological and multimodal imaging
      studies are needed to elucidate the precise morphological and pathogenetic
      background of the detected echosignal pathology, and also to correlate these
      findings to the various clinical features of this disease entity.

PMID- 20692506
TI  - Transcranial sonography in Huntington's disease.
AB  - Transcranial sonography (TCS) has become a reliable and sensitive diagnostic tool
      in the evaluation of extrapyramidal movement disorders, especially in the
      differentiation of Parkinsonian syndromes. Although only rarely reported, TCS
      reveals also signal alterations of basal ganglia in Huntington's disease (HD).
      Distinct findings are related to all of the three symptom domains of the clinical
      triad of the disease. The TCS finding of substantia nigra hyperechogenicity was
      related to higher clinical disease severity. A poorer cognitive performance
      correlated with larger width of third ventricle. Moreover, widths of frontal
      horns of lateral ventricles measured with TCS corresponded closely to diameters
      estimated by CT imaging. Depressive symptoms were found to be associated with
      abnormal echogenicity of mesencephalic raphe structures. Furthermore, a larger
      number of CAG repeats in the huntingtin gene correlated with presence of SN
      hyperechogenicity. This review provides information about the examination
      procedure and its diagnostic value in HD. Possible morphological and
      pathophysiological mechanisms leading to changes in the reflection of ultrasound
      waves are discussed in the context of established neuroimaging modalities.

PMID- 20692507
TI  - Transcranial sonography in depression.
AB  - Transcranial sonography, which displays tissue echogenicity of the brain through
      the intact skull, reveals reduced echogenicity of the brainstem raphe (BR) as a
      characteristic finding in unipolar depression and in depression associated with
      Parkinson's or Wilson's disease, but in general not in healthy adults, bipolar
      affective disorders, schizophrenia, multiple sclerosis with depression, or
      Parkinson's disease without concomitant depression. The reason for the reduced
      echogenicity of the BR is not entirely clear. Magnetic resonance imaging
      investigations, however, provide evidence that the signal alteration may be
      caused by a modification of tissue cell density, the interstitial matrix
      composition, or an alteration of fiber tracts integrity. An involvement of the
      basal limbic system in the pathogenesis of unipolar depression and depression
      associated with certain neurodegenerative diseases is assumed.

PMID- 20692508
TI  - Transcranial sonography-assisted stereotaxy and follow-up of deep brain implants
      in patients with movement disorders.
AB  - Transcranial sonography (TCS) of the brain parenchyma meanwhile allows a high
      resolution imaging of deep brain structures in the majority of adults. Two pilot
      studies have demonstrated that the intraoperative visualization with TCS and the
      TCS-assisted insertion of deep-brain stimulation (DBS) electrodes into the
      subthalamic nucleus and the globus pallidus interna are feasible and safe
      provided there is exact knowledge on the extent of electrode TCS imaging
      artifacts. Moreover, TCS can be recommended for the postoperative monitoring of
      DBS electrode position. Dislocation of a DBS electrode can be easily detected. It
      is likely that the obvious advantages of TCS will promote its increasing use for
      the intra- and postoperative monitoring of deep brain implants.

PMID- 20692509
TI  - Transcranial sonography in movement disorders. Conclusions.

PMID- 20692511
TI  - New 50 million pound cancer fund already intellectually bankrupt.

PMID- 20692512
TI  - DSM-5: diagnosis of mental disorders.

PMID- 20692513
TI  - Water and sanitation become human rights, albeit turbidly.

PMID- 20692514
TI  - In-vivo tissue engineering of biological joint replacements.

PMID- 20692515
TI  - Singapore embraces international research integrity.

PMID- 20692517
TI  - The price of success.

PMID- 20692519
TI  - Prognostic significance of blood-pressure variability.

PMID- 20692520
TI  - Prognostic significance of blood-pressure variability.

PMID- 20692521
TI  - Prognostic significance of blood-pressure variability.

PMID- 20692524
TI  - Beta blockers in hypertension.

PMID- 20692525
TI  - The Global Fund: replenishment and redefinition.

PMID- 20692526
TI  - Food crisis in Niger: a chronic emergency.

PMID- 20692527
TI  - H1N1 vaccine safety: real-time surveillance in the UK.

PMID- 20692528
TI  - Plain cigarette packs: a creative challenge for Big Tobacco.

PMID- 20692529
TI  - Screening for chronic kidney disease in sub-Saharan Africa.

PMID- 20692530
TI  - Regeneration of the articular surface of the rabbit synovial joint by cell
      homing: a proof of concept study.
AB  - BACKGROUND: A common approach for tissue regeneration is cell delivery, for
      example by direct transplantation of stem or progenitor cells. An alternative, by
      recruitment of endogenous cells, needs experimental evidence. We tested the
      hypothesis that the articular surface of the synovial joint can regenerate with a
      biological cue spatially embedded in an anatomically correct bioscaffold.
      METHODS: In this proof of concept study, the surface morphology of a rabbit
      proximal humeral joint was captured with laser scanning and reconstructed by
      computer-aided design. We fabricated an anatomically correct bioscaffold using a
      composite of poly-epsilon-caprolactone and hydroxyapatite. The entire articular
      surface of unilateral proximal humeral condyles of skeletally mature rabbits was
      surgically excised and replaced with bioscaffolds spatially infused with
      transforming growth factor beta3 (TGFbeta3)-adsorbed or TGFbeta3-free collagen
      hydrogel. Locomotion and weightbearing were assessed 1-2, 3-4, and 5-8 weeks
      after surgery. At 4 months, regenerated cartilage samples were retrieved from in
      vivo and assessed for surface fissure, thickness, density, chondrocyte numbers,
      collagen type II and aggrecan, and mechanical properties. FINDINGS: Ten rabbits
      received TGFbeta3-infused bioscaffolds, ten received TGFbeta3-free bioscaffolds,
      and three rabbits underwent humeral-head excision without bioscaffold
      replacement. All animals in the TGFbeta3-delivery group fully resumed
      weightbearing and locomotion 3-4 weeks after surgery, more consistently than
      those in the TGFbeta3-free group. Defect-only rabbits limped at all times. 4
      months after surgery, TGFbeta3-infused bioscaffolds were fully covered with
      hyaline cartilage in the articular surface. TGFbeta3-free bioscaffolds had only
      isolated cartilage formation, and no cartilage formation occurred in defect-only
      rabbits. TGFbeta3 delivery yielded uniformly distributed chondrocytes in a matrix
      with collagen type II and aggrecan and had significantly greater thickness
      (p=0.044) and density (p<0.0001) than did cartilage formed without TGFbeta3.
      Compressive and shear properties of TGFbeta3-mediated articular cartilage did not
      differ from those of native articular cartilage, and were significantly greater
      than those of cartilage formed without TGFbeta3. Regenerated cartilage was
      avascular and integrated with regenerated subchondral bone that had well defined
      blood vessels. TGFbeta3 delivery recruited roughly 130% more cells in the
      regenerated articular cartilage than did spontaneous cell migration without
      TGFbeta3. INTERPRETATION: Our findings suggest that the entire articular surface
      of the synovial joint can regenerate without cell transplantation. Regeneration
      of complex tissues is probable by homing of endogenous cells, as exemplified by
      stratified avascular cartilage and vascularised bone. Whether cell homing acts as
      an adjunctive or alternative approach of cell delivery for regeneration of
      tissues with different organisational complexity warrants further investigation.
      FUNDING: New York State Stem Cell Science; US National Institutes of Health.

PMID- 20692531
TI  - Cough syncope--a diagnosis under pressure.

PMID- 20692532
TI  - Immunobiology. Editorial.

PMID- 20692533
TI  - Comprehensive analysis of TLR4-induced transcriptional responses in interleukin 4
      primed mouse macrophages.
AB  - Interferon (IFN)gamma and interleukin (IL)-4 are central regulators of T helper 1
      (Th1) and T helper 2 (Th2) immune responses, respectively. Both cytokines have a
      major impact on macrophage phenotypes: IFNgamma-priming and subsequent TLR4
      activation induces so-called "classically activated" macrophages that are
      characterized by pronounced pro-inflammatory responses, whereas IL-4-treated
      macrophages, commonly called "alternatively activated", are known to develop
      enhanced capacity for endocytosis, antigen presentation and tissue repair and are
      generally considered anti-inflammatory. Considering IL-4 as priming rather than
      activating stimulus, we now compared the TLR4-dependent global gene activation
      program in IFNgamma- versus IL-4-pretreated mouse macrophages, which has rarely
      been studied so far. Although both cytokines frequently induced opposing effects
      on gene transcription, the subsequent activation of bone marrow-derived
      macrophages by lipopolysaccharide (LPS) produced a strong, priming-dependent pro
      inflammatory response in both macrophage types. For example, the production of
      key pro-inflammatory cytokines IL-6 and IL-12 was significantly higher in IL-4-
      versus IFNgamma-primed macrophages and several cytokine genes, including Il19,
      Ccl17, Ccl22, Ccl24 and Cxcl5, were preferentially induced in "alternatively"
      primed and LPS activated mouse macrophages. In a subset of genes, including
      IL12a, IFNgamma-priming was actually found to suppress LPS-induced gene
      expression in a Stat1-dependent manner. Our data suggest that IL-4-priming is not
      per se anti-inflammatory but generates a macrophage that is "tissue protective"
      but still capable of mounting a strong inflammatory response after TLR4-dependent
      activation.

PMID- 20692534
TI  - IL-10 regulation of macrophage VEGF production is dependent on macrophage
      polarisation and hypoxia.
AB  - Vascular endothelial growth factor A (VEGF) is critical for vascular remodelling
      during tissue repair subsequent to inflammation or injury, but under pathological
      conditions, VEGF induces tissue damaging angiogenesis. Macrophages generate VEGF
      that supports angiogenesis, when they adapt to their environment and respond with
      a co-ordinated set of signals to promote or resolve inflammation. Depending on
      the stimulus, the phenotype of macrophage activation is broadly classified into
      M1 (NOS2(+)) and M2 (arginase-1(+)). In recent studies, IL-10, an anti
      inflammatory cytokine that suppresses the M1 phenotype, has been shown to dampen
      the angiogenic switch and subsequent neovascularisation. However, as we show
      here, these effects are context dependent. In this study, we have demonstrated
      that IL-10 inhibits M1 bone marrow-derived macrophages (BMDMs) VEGF, stimulated
      by LPS/CGS21680 (adenosine A2A receptor agonist), but does not prevent VEGF
      production from M2 macrophages stimulated with prostaglandin E2 (PGE2).
      Furthermore, we show that hypoxic-conditioned BMDM generated VEGF was maintained
      in the presence of IL-10, but was suppressed when concomitantly stimulated with
      IFN-gamma. Finally, LPS/PGE2 generated an arginase-1(+) M2 macrophage that in
      addition to generating VEGF produced significant quantities of IL-10. Under these
      conditions, neither in IL-10 deficient macrophages nor following IL-10
      neutralization was VEGF production affected. Our results indicate IL-10
      suppressed M1 but not M2 derived VEGF, and that activation signals determined the
      influence of IL-10 on VEGF production. Consequently, therapies to suppress
      macrophage activation that as a result generate IL-10, or utilising IL-10 as a
      potential anti-angiogenic therapy, may result in a paradoxical support of
      neovascularisation and thus on-going tissue damage or aberrant repair.

PMID- 20692536
TI  - Autoantibody testing for autoimmune disease.
AB  - The proper use and interpretation of serologic testing for diagnosing autoimmune
      diseases presents a challenge to clinicians for several reasons. Most laboratory
      tests for autoimmune disease are significantly less than 100% sensitive or
      specific. In addition, different techniques for the same antibody test may give
      different results, such as indirect immunofluorescence and multiplex bead assay
      for antinuclear antibody. Autoantibody testing should only be performed in the
      context of the clinical workup of patients who have a reasonable likelihood of
      having the disease for which the testing is relevant. Otherwise, the predictive
      value of a positive test is too low. Particularly with antinuclear antibody and
      antineutrophil cytoplasmic antibody testing, clinicians must know the methodology
      through which the tests are being performed, and should develop a relationship
      with the laboratory pathologist so that inconsistent or surprising results can be
      investigated.

PMID- 20692537
TI  - Utility of bronchoalveolar lavage in evaluation of patients with connective
      tissue diseases.
AB  - Pulmonary involvement is common in patients with connective tissue diseases
      (CTDs), and significantly contributes to morbidity and mortality in this patient
      population. There are different forms of lung pathology in CTDs, which include
      primary involvement such as interstitial lung disease or pulmonary hemorrhage,
      and pulmonary complications resulting from other CTD-related organ involvement
      including aspiration pneumonia due to muscle weakness or esophageal fibrosis.
      Moreover, iatrogenic lung disease, such as medication-induced hypersensitivity
      pneumonitis or opportunistic infections due to immunosuppression, may develop.
      Appropriate treatment of pulmonary complications in patients with CTDs requires
      careful diagnostic workup because different forms of lung involvement may
      overlap, causing similar clinical manifestations and similar radiological or
      functional impairment. Moreover, in view of the broad variability of clinical
      course of CTD-related interstitial lung disease, identification of biomarkers
      helpful in predicting prognosis becomes of key importance. In addition to
      radiological assessment and functional testing that provide information regarding
      localization and severity of lung disease, bronchoalveolar lavage (BAL) appears
      helpful in revealing the nature of lung pathology and intensity of lung
      inflammation through sampling of cells and fluid from the lower respiratory
      tract. The aim of this article is to critically review available data concerning
      the evaluation of BAL cytology in different forms of lung disease associated with
      CTDs.

PMID- 20692538
TI  - Pulmonary manifestations of scleroderma and mixed connective tissue disease.
AB  - Pulmonary manifestations are common in connective tissue diseases, and are
      associated with significant morbidity and mortality in this patient population.
      Systemic sclerosis (SSc) and mixed connective tissue disease (MCTD) are clinical
      entities for which the detection of lung involvement is essential to improve
      patient care and outcomes. This article discusses the pathogenesis, clinical
      presentation, and evaluation of the patient with pulmonary disease related to SSc
      and MCTD, with an emphasis on interstitial lung disease and pulmonary
      hypertension.

PMID- 20692539
TI  - Pulmonary manifestations of rheumatoid arthritis.
AB  - Pulmonary disease is a major source of morbidity and mortality in rheumatoid
      arthritis, manifesting most commonly as interstitial lung disease, airways
      disease, rheumatoid nodules, and pleural effusions. The diagnostic assessment of
      respiratory abnormalities is complicated by underlying risk for infection, the
      use of drugs with known pulmonary toxicity, and the frequency of lung disease
      related to rheumatoid arthritis itself. Evaluation and management of rheumatoid
      arthritis-associated pulmonary disease frequently necessitates a
      multidisciplinary approach.

PMID- 20692540
TI  - Pulmonary manifestations of systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a potentially severe, frequently disabling
      autoimmune disease with multiorgan involvement and a typically waxing and waning
      course. SLE is often considered the prototypical autoimmune disease. Although SLE
      has the potential to affect any organ, the lungs are commonly involved later in
      the course of the disease in the setting of other organ involvement. Pulmonary
      disease may complicate SLE and is an important cause of morbidity and mortality.
      The most common pulmonary manifestation attributable to SLE is pleuritis, but
      other pleural involvement can be seen, as well as parenchymal disease, pulmonary
      vascular disease, diaphragmatic dysfunction, and upper airway dysfunction.
      Finding the true prevalence of lung involvement with SLE is complicated by the
      high rates of pulmonary infections. This article reviews the diverse clinical
      symptoms and immunologic pulmonary manifestations of SLE.

PMID- 20692541
TI  - Pulmonary involvement in Sjogren syndrome.
AB  - Sjogren syndrome is a slowly progressing autoimmune disease. Pulmonary
      manifestations are frequent in primary Sjogren syndrome but often not clinically
      significant; the most common are xerotrachea, interstitial lung diseases, and
      small airway obstruction. Pulmonary manifestations in Sjogren syndrome have a
      slow progression and favorable prognosis, with the exception of primary pulmonary
      lymphoma and pulmonary hypertension.

PMID- 20692542
TI  - Pulmonary manifestations of the idiopathic inflammatory myopathies.
AB  - Pulmonary involvement in myositis includes interstitial lung disease (ILD),
      respiratory muscle weakness, aspiration, infections, and drug-induced disease.
      ILD may precede myositis, and results in increased morbidity and mortality rates.
      Initial evaluation should include pulmonary function tests and high-resolution
      computed tomography. Nonspecific interstitial pneumonia (NSIP) is the most common
      histologic pattern on lung biopsy. Treatment usually consists of a combination of
      steroids and other immunosuppressive agents, and the response depends on the
      clinical presentation and underlying histology.

PMID- 20692543
TI  - Pulmonary manifestations of relapsing polychondritis.
AB  - Relapsing polychondritis (RP) is a chronic multisystemic disease characterized by
      recurrent episodes of cartilage inflammation throughout the body. The lower
      respiratory tract is involved in 20% to 50% of patients and results in
      significant morbidity. Effective medical therapies and airway interventions are
      available in experienced centers; however, no single treatment is curative, and
      the prognosis of RP with airway disease remains overall guarded.

PMID- 20692544
TI  - The pulmonary vasculitides.
AB  - The vasculitides represent a spectrum of disorders characterized by inflammation
      and destruction of the blood vessel wall, and these entities commonly affect the
      respiratory system. Although challenging to diagnose and manage, recent advances
      in the treatment of these disorders has greatly improved the prognosis for
      patients with vasculitis, and with the advent of increasingly less toxic
      therapies, the future for these patients is brighter still.

PMID- 20692545
TI  - Pulmonary manifestations of the antiphospholipid antibody syndrome.
AB  - A broad spectrum of pulmonary disease may occur in antiphospholipid antibody
      syndrome. The most common pulmonary manifestations are pulmonary thromboembolism
      and pulmonary hypertension. In this article the authors review these
      manifestations, as well as less common findings including acute respiratory
      distress syndrome, alveolar hemorrhage, and pulmonary capillaritis.

PMID- 20692546
TI  - Pulmonary manifestations of ankylosing spondylitis.
AB  - Ankylosing spondylitis, a chronic multisystem inflammatory disorder, can present
      with articular and extra-articular features. It can affect the tracheobronchial
      tree and the lung parenchyma, and respiratory complications include chest wall
      restriction, apical fibrobullous disease with or without secondary pulmonary
      superinfection, spontaneous pneumothorax, and obstructive sleep apnea. Ankylosing
      spondylitis is a common cause of pulmonary apical fibrocystic disease; early
      involvement may be unilateral or asymmetrical, but most cases eventually consist
      of bilateral apical fibrobullous lesions, many of which are progressive with
      coalescence of the nodules, formation of cysts and cavities, fibrosis, and
      bronchiectasis. Mycobacterial or fungal superinfection of the upper lobe cysts
      and cavities occurs commonly. Aspergillus fumigatus is the most common pathogen
      isolated, followed by various species of mycobacteria. Prognosis of patients with
      fibrobullous apical lesions is mainly determined by the presence, extent, and
      severity of superinfection. Pulmonary function test results are nonspecific and
      generally parallel the severity of parenchymal involvement. A restrictive
      ventilatory impairment can develop in patients with ankylosing spondylitis
      because of either fusion of the costovertebral joints and ankylosis of the
      thoracic spine or anterior chest wall involvement. Chest radiographic findings
      may mirror the severity of clinical involvement. Pulmonary parenchymal disease is
      typically progressive, and cyst formation, cavitation, and fibrosis are seen in
      advanced cases. No treatment has been shown to alter the clinical course of
      apical fibrobullous disease. Although several antiinflammatory agents, such as
      infliximab, etanercept, and adalimumab, are being used to treat ankylosing
      spondylitis, their effects on pulmonary manifestations are unclear.

PMID- 20692547
TI  - Osteoporosis and bone health in patients with lung disease.
AB  - Osteoporosis is a common systemic disease whose presentation crosses many
      specialties in medicine. Low bone mass, (osteopenia) and osteoporosis increases a
      patient's risk of suffering from a fracture, and fragility fractures are known to
      have a significant effect on morbidity and mortality, with up to a 1-year 20%
      mortality risk. Early detection of osteoporosis is essential to reduce a
      patient's risk of fracture. Several diseases are associated with an increased
      risk of osteoporosis because of the medications used to treat these diseases,
      including but not limited to the prescribing of glucocorticoids. It is important
      to recognize which patients warrant therapy for bone health and to implement
      medical management as appropriate.

PMID- 20692548
TI  - Toxicity and monitoring of immunosuppressive therapy used in systemic autoimmune
      diseases.
AB  - Systemic autoimmune diseases may be progressive and lead to organ system
      dysfunction and premature death. Current treatment paradigms are usually
      predominantly based on the administration of immunosuppressive and/or
      immunomodulatory drug therapy. Such therapy can stabilize systemic manifestations
      of connective tissue disease (CTD) and may put the disease into remission, and
      many of these agents are commonly used to treat CTD-associated interstitial lung
      disease (ILD). Although these agents have largely revolutionized the treatment of
      the systemic autoimmune diseases, adverse reactions, which can be serious and
      life threatening, to the various immunosuppressive agents used in the treatment
      of CTD can occur. Treating physicians must be aware of mechanisms of action of
      various immunosuppressive agents and be able to recognize the potential adverse
      reactions that may occur with therapy as well as potentially harmful effects on
      fetal development. Appropriate monitoring may prevent or limit toxicity from
      these agents, and knowledge of drug-drug interactions is essential when these
      agents are prescribed.

PMID- 20692549
TI  - Lung transplantation in autoimmune diseases.
AB  - In the last 45 years, lung transplantation has evolved from its status as a rare
      extreme form of surgical therapy for the treatment of advanced lung diseases to
      an accepted therapeutic option for select patients. Although pulmonary fibrosis
      and pulmonary vascular diseases are important indications for lung
      transplantation, only a small percentage of transplants are performed in patients
      with collagen vascular diseases. The reasons for this low number are
      multifactorial. This article reviews issues relevant to all lung transplant
      candidates and recipients as well as those specific to patients with autoimmune
      diseases.

PMID- 20692550
TI  - Predictors of ethanol consumption in adult Sprague-Dawley rats: relation to
      hypothalamic peptides that stimulate ethanol intake.
AB  - To investigate mechanisms in outbred animals that increase the propensity to
      consume ethanol, it is important to identify and characterize these animals
      before or at early stages in their exposure to ethanol. In the present study,
      different measures were examined in adult Sprague-Dawley rats to determine
      whether they can predict long-term propensity to overconsume ethanol. Before
      consuming 9% ethanol with a two-bottle choice paradigm, rats were examined with
      the commonly used behavioral measures of novelty-induced locomotor activity and
      anxiety, as assessed during 15 min in an open-field activity chamber. Two
      additional measures, intake of a low 2% ethanol concentration or circulating
      triglyceride (TG) levels after a meal, were also examined with respect to their
      ability to predict chronic 9% ethanol consumption. The results revealed
      significant positive correlations across individual rats between the amount of 9%
      ethanol ultimately consumed and three of these different measures, with high
      scores for activity, 2% ethanol intake, and TGs identifying rats that consume
      150% more ethanol than rats with low scores. Measurements of hypothalamic
      peptides that stimulate ethanol intake suggest that they contribute early to the
      greater ethanol consumption predicted by these high scores. Rats with high 2%
      ethanol intake or high TGs, two measures found to be closely related, had
      significantly elevated expression of enkephalin (ENK) and galanin (GAL) in the
      hypothalamic paraventricular nucleus (PVN) but no change in neuropeptide Y (NPY)
      in the arcuate nucleus (ARC). This is in contrast to rats with high activity
      scores, which in addition to elevated PVN ENK expression showed enhanced NPY in
      the ARC but no change in GAL. Elevated ENK is a common characteristic related to
      all three predictors of chronic ethanol intake, whereas the other peptides
      differentiate these predictors, with GAL enhanced with high 2% ethanol intake and
      TG measures but NPY related to activity.

PMID- 20692551
TI  - Diverse effects of ethanol on Ca2+ entry and subsequent aggregation of platelets.
AB  - Although alcohol is known to inhibit platelet aggregation, and transplasmalemmal
      Ca(2+) entry is profoundly involved in platelet aggregation, there has been
      limited knowledge about the relationship between alcohol and Ca(2+) entry. The
      purpose of this study was to determine whether and how ethanol in vitro affects
      Ca(2+) entry through different pathways and the subsequent aggregation of
      platelets. Thapsigargin, 1-oleoyl-2-acetyl-sn-glycerol (OAG), and thrombin were
      used to stimulate human platelets. Ca(2)(+) entry and the subsequent aggregatory
      responses of platelets were measured by spectrofluorometry using fura-2/AM as an
      indicator and the light transmission method, respectively. Thapsigargin-induced
      Ca(2+) entry and the following platelet aggregation were significantly inhibited
      by ethanol at concentrations of 0.5% or more. OAG-induced Ca(2+) entry was
      significantly augmented by ethanol at concentrations of 0.5% or more, whereas
      platelet aggregation by OAG was significantly inhibited by ethanol at
      concentrations of 0.5 % or more. Thrombin-induced Ca(2+) entry was not
      significantly affected by ethanol up to 2%, whereas platelet aggregation by
      thrombin was markedly inhibited by ethanol at concentrations of 0.5% or more.
      Thrombin-induced Ca(2+) entry in the presence of SKF-96365 was augmented by
      pretreatment with ethanol. Ethanol in vitro showed diverse effects on the
      different Ca(2+) entry pathways of platelets, whereas aggregatory responses
      induced by activation of the different Ca(2+) entry pathways of platelets were
      all inhibited by ethanol. These results suggest that ethanol inhibits platelet
      aggregation mainly via a mechanism(s) other than transplasmalemmal Ca(2+) entry.

PMID- 20692552
TI  - Intraocular lens calculations: call for more deterministic models.

PMID- 20692553
TI  - Optic capture in the anterior capsulorhexis during combined cataract and
      vitreoretinal surgery.
AB  - We describe an optic capture technique that can be used during combined cataract
      and vitreoretinal surgery if in-the-bag implantation of an intraocular lens (IOL)
      is not possible. The IOL is placed in the ciliary sulcus, and optic capture is
      performed behind an intact anterior continuous curvilinear capsulorhexis, with
      the haptics remaining in the sulcus. The technique maintains IOL stability and
      separation of the anterior and posterior segments intraoperatively and
      postoperatively.

PMID- 20692554
TI  - Microwash or macrowash technique to maintain a clear cornea during cataract
      surgery.
AB  - We describe a technique of irrigating and thereby rapidly and effectively
      clearing the cornea of relatively large amounts of surface contaminants that
      reduce surgical visibility and may contribute to endophthalmitis. This technique
      is referred to as "macrowash." If the technique is required, it is usually at the
      commencement of cataract surgery, immediately after placement of the surgical
      drape. The technique not only saves time, but also reduces the volume of
      irrigating solution required by the "microwash" technique, which is traditionally
      carried out by the scrub nurse/surgical assistant using a Rycroft cannula
      attached to a 15 mL container of irrigating solution.

PMID- 20692555
TI  - Intraocular lens power calculation after myopic excimer laser surgery: clinical
      comparison of published methods.
AB  - PURPOSE: To compare results of intraocular lens (IOL) power calculation methods
      after myopic excimer laser surgery. SETTING: Private practice. METHODS: In this
      prospective study, eyes having phacoemulsification after myopic excimer laser
      surgery were classified into Group 1 (preoperative corneal power available,
      refractive change known), Group 2 (preoperative corneal power available,
      refractive change uncertain), and Group 3 (preoperative corneal power
      unavailable, refractive change known even if uncertain). The IOL power was
      calculated using the following methods: clinical history, Awwad,
      Camellin/Calossi, Diehl, Feiz, Ferrara, Latkany, Masket, Rosa, Savini, Shammas,
      Seitz/Speicher, and Seitz/Speicher/Savini. RESULTS: The lowest mean absolute
      errors (MAEs) in IOL power prediction in Group 1 (n = 12) and Group 2 (n = 11),
      respectively, were with the methods of Seitz/Speicher/Savini (0.51 diopter [D] +/
      0.44 [SD] and 0.55 +/- 0.50 D), Seitz/Speicher (0.58 +/- 0.47 D and 0.54 +/-
      0.45 D), Savini (0.60 +/- 0.44 D and 0.65 +/- 0.63 D), Masket (0.82 +/- 0.49 D
      and 0.69 +/- 0.51 D), and Shammas (0.77 +/- 0.43 D and 1.11 +/- 0.50 D). In Group
      3 (n = 5), the lowest MAEs were with the methods of Masket (0.23 +/- 0.27 D),
      Savini (0.49 +/- 0.86 D), Seitz/Speicher/Savini (0.68 +/- 0.36 D), Shammas (0.84
      +/- 0.98 D), and Camellin/Calossi (0.91 +/- 0.84 D). CONCLUSIONS: When corneal
      power is known, the Seitz/Speicher method (with or without Savini adjustment)
      seems the best solution to obtain an accurate IOL power prediction. Otherwise,
      the Masket method may be the most reliable option.

PMID- 20692556
TI  - Evaluation of intraocular lens power prediction methods using the American
      Society of Cataract and Refractive Surgeons Post-Keratorefractive Intraocular
      Lens Power Calculator.
AB  - PURPOSE: To evaluate the accuracy of methods of intraocular lens (IOL) power
      prediction after previous laser in situ keratomileusis (LASIK) or photorefractive
      keratectomy (PRK) using the American Society of Cataract and Refractive Surgery
      IOL power calculator. SETTING: Cullen Eye Institute, Baylor College of Medicine,
      Houston, Texas, and private practice, Mesa, Arizona, USA. METHODS: The following
      methods were evaluated: methods using pre-LASIK/PRK keratometry (K) and
      surgically induced change in refraction, methods using surgically induced change
      in refraction, and methods using no previous data. The predicted IOL power was
      calculated with each method using the actual refraction after cataract surgery as
      the target. The IOL prediction error was calculated as the implanted IOL power
      minus the predicted IOL power. Arithmetic and absolute IOL prediction errors,
      variances in mean arithmetic IOL prediction error, and percentage of eyes within
      +/-0.50 diopter (D) and +/-1.00 D of refractive prediction errors were
      calculated. RESULTS: Methods using surgically induced change in refraction or no
      previous data had significantly smaller mean absolute IOL prediction errors,
      smaller variances, and a greater percentage of eyes within +/-0.50 D and +/-1.00
      D of refractive prediction errors than methods using pre-LASIK/PRK keratometry
      (K) values and surgically induced change in refraction (all P<.05 with Bonferroni
      correction). There were no statistically significant differences between methods
      using surgically induced change in refraction and methods using no previous data.
      CONCLUSION: Methods using surgically induced change in refraction and methods
      using no previous data gave better results than methods using pre-LASIK/PRK K
      values and surgically induced change in refraction.

PMID- 20692557
TI  - Precision of biometry, keratometry, and refractive measurements with a partial
      coherence interferometry-keratometry device.
AB  - PURPOSE: To evaluate the precision of the axial length (AL), keratometry (K),
      anterior chamber depth (ACD), astigmatism, and minus astigmatic cylinder axis
      measurements by a partial coherence interferometry (PCI)-keratometry device.
      SETTING: Private practice, Lynwood, California. METHODS: This prospective
      comparative observational study analyzed measurements in the second eye to have
      cataract surgery. Before surgery in the first eye, AL, K, ACD, astigmatism, and
      cylinder axis in both eyes were measured with an IOLMaster PCI device. The
      measurements were repeated approximately 1 month later, before second eye
      surgery. The 2 sets of measurements were compared. RESULTS: The study evaluated
      121 eyes of 121 patients. The interclass correlation coefficient (ICC) for AL was
      0.999 in all 3 signal-to-noise ratio (SNR) categories; the highest difference
      range was with an SNR below 100. Astigmatism, K, and cylinder axis had a high
      correlation in flat corneas (K reading <42.0 diopters [D]) (ICC = 0.994, 0.978,
      and 0.918, respectively) and a poorer correlation with K readings between 42.0 D
      and 44.0 D (ICC = 0.905, 0.774, and 0.456, respectively) and K readings above
      44.0 D (ICC = 0.988, 0.729 and 0.446, respectively). CONCLUSIONS: The precision
      of the PCI measurements was extremely high for AL with low fluctuations (95%
      limits of agreement [LoA], 0.06 mm) and was relatively high for K readings with
      higher fluctuations (95% LoA, 0.55 D) and for ACD (95% LoA, 0.2 mm). The
      precision of astigmatism and cylinder axis was high in flat corneas and
      relatively low in steeper corneas.

PMID- 20692558
TI  - Analysis of biometry and prevalence data for corneal astigmatism in 23,239 eyes.
AB  - PURPOSE: To present and analyze biometry data sets and prevalence data for
      corneal astigmatism in a large population. SETTING: High-volume eye surgery
      center, Castrop-Rauxel, Germany. METHODS: Axial length (AL), corneal radii,
      anterior chamber depth (ACD), and horizontal corneal diameter (white-to-white
      [WTW] distance) were optically measured by partial coherence interferometry
      (IOLMaster). Patient data sets acquired between 2000 and 2006 were reviewed and
      analyzed. RESULTS: The study evaluated 23,239 data sets of 15,448 patients with a
      median age of 74 years. The mean values were as follows: AL, 23.43 mm +/- 1.51
      (SD); corneal radius, 7.69 +/- 0.28 mm; WTW distance, 11.82 +/- 0.40 mm; and ACD,
      3.11 +/- 0.43 mm. The ACD and axis of astigmatism were correlated with age. The
      AL, corneal radius, ACD, and WTW were correlated with one other. Eight percent of
      eyes had corneal astigmatism greater than 2.00 diopters (D), and 2.6% had more
      than 3.00 D. Astigmatism was with the rule (WTW) in 46.8% of eyes, against the
      rule in 34.4%, and oblique in 18.9%. High astigmatism was predominantly WTW.
      CONCLUSIONS: The results in this analysis might provide normative data for
      cataract patients and a useful reference for multiple purposes. The correlation
      of AL with corneal radius, ACD, and corneal diameter in normal eyes was not
      present in eyes with extreme myopia or hyperopia.

PMID- 20692559
TI  - Anterior chamber phakic intraocular lens implantation in children to treat severe
      anisometropic myopia and amblyopia: 3-year clinical results.
AB  - PURPOSE: To evaluate the midterm efficacy of Verisyse anterior chamber phakic
      intraocular lens (AC pIOL) implantation in reducing clinically significant (>-8.0
      diopters) myopic anisometropia in children who have been noncompliant with
      traditional medical treatment. SETTING: Private practice in affiliation with San
      Diego Children's Hospital, San Diego, California, USA. METHODS: A retrospective
      interventional chart review identified highly anisometropic myopic pediatric
      patients in a single practice who had AC pIOL implantation in the more myopic
      eye. None of the patients were compliant with spectacle correction or contact
      lens therapy, and all had dense amblyopia. Preoperative and postoperative visual
      acuity, stereoacuity, central corneal thickness, motor alignment, and endothelial
      cell counts were performed in all patients. Occlusion therapy was initiated
      subsequent to pIOL implantation. RESULTS: The review identified 7 patients
      ranging in age from 5 to 11 years; the postoperative follow-up was 34 to 36
      months. All patients had a significant improvement (>6 lines) in visual acuity
      postoperatively. The mean corrected distance visual acuity was 20/40 at 3 years.
      All patients had improved stereoacuity Randot testing, from a mean of 0 seconds
      of arc preoperatively to a mean of 185 seconds of arc at 3 years. No
      intraoperative or postoperative complications were identified. CONCLUSIONS:
      Results indicate that AC pIOL implantation can be considered an alternative
      modality to manage clinically significant, severe anisometropic myopia in
      pediatric eyes when there is poor patient compliance with traditional medical
      treatment. Long-term follow-up of corneal endothelial cell density after
      pediatric AC pIOL implantation is strongly encouraged.

PMID- 20692560
TI  - Outcomes of cataract surgery and intraocular lens implantation with and without
      intracameral triamcinolone in pediatric eyes.
AB  - PURPOSE: To evaluate whether intracameral triamcinolone has an effect on anterior
      segment inflammation and visual axis obscuration after pediatric cataract surgery
      with intraocular (IOL) implantation. SETTING: Iladevi Cataract and IOL Research
      Institute, Ahmedabad, India. METHODS: This retrospective age-matched case-control
      study comprised consecutive eyes of children having phacoaspiration, posterior
      capsulectomy, vitrectomy, and IOL implantation. In the study group, eyes received
      a standardized application of an intracameral preservative-free triamcinolone
      acetonide suspension intraoperatively. In the control group, age-matched
      consecutive eyes had surgery with a similar technique but without intracameral
      preservative-free triamcinolone acetonide. Cell deposits, posterior synechias,
      visual axis obscuration, and intraocular pressure (IOP) were evaluated 1 month
      and 12 months postoperatively. RESULTS: The mean patient age at surgery was 9.15
      months +/- 5.04 (SD) in the study group (41 eyes) and 9.34 +/- 5.10 months in the
      control group (83 eyes) (P = .91). The visual axis was not obscured in any eye in
      the study group, while 9 eyes (10.8%) in the control group had an obscured axis;
      the difference between groups was statistically significant (P<.029). Six eyes
      (7.2%) in the control group required secondary membranectomy with pars plana
      vitrectomy. There was a statistically significant difference between the 2 groups
      in posterior synechias and cell deposits (both P<.033) and no significant
      difference in preoperative or postoperative IOP (P = .29 and P = .50,
      respectively). CONCLUSION: Pediatric eyes receiving intracameral triamcinolone
      intraoperatively had significantly less anterior segment inflammation and no
      visual axis obscuration after cataract surgery with IOL implantation.

PMID- 20692561
TI  - Aqueous penetration of moxifloxacin 0.5% ophthalmic solution and besifloxacin
      0.6% ophthalmic suspension in cataract surgery patients.
AB  - PURPOSE: To determine the aqueous humor concentrations of moxifloxacin and
      besifloxacin after routine preoperative topical dosing in patients having
      cataract surgery. SETTING: Wilmer Eye Institute, Johns Hopkins University,
      Baltimore, Maryland, USA. METHODS: In this prospective randomized parallel double
      masked clinical trial, 1 drop of commercially available moxifloxacin 0.5%
      ophthalmic solution or besifloxacin 0.6% ophthalmic suspension was administered
      every 10 minutes for a total of 4 doses beginning 1 hour before routine cataract
      surgery. Aqueous humor was sampled via the paracentesis, and antibiotic
      concentrations were determined using validated high-performance liquid
      chromatography procedures. RESULTS: The study enrolled 50 patients. The aqueous
      concentration of the antibiotic agent was detectable in all 23 moxifloxacin
      samples and in 10 (40%) of the 25 besifloxacin samples (P<.0001, Pearson chi
      square test). The mean aqueous concentration in the moxifloxacin samples was 50
      fold higher than in the besifloxacin samples (1.6108 microg/mL versus 0.0319
      microg/mL) when all samples were included (P<.0001, Wilcoxon test), while the
      moxifloxacin concentration was 38-fold higher than the besifloxacin concentration
      (1.6108 microg/mL versus 0.0422 microg/mL) in the samples with detectable
      antibiotic agent (P<.0001). CONCLUSIONS: After topical preoperative
      administration, moxifloxacin 0.5% ophthalmic solution had a 38-fold to 50-fold
      higher concentration in the aqueous humor than besifloxacin 0.6% ophthalmic
      suspension. Besifloxacin was undetectable in more than half the aqueous humor
      samples.

PMID- 20692562
TI  - Transconjunctival single-plane sclerocorneal incisions versus clear corneal
      incisions in cataract surgery.
AB  - PURPOSE: To compare a transconjunctival single-plane sclerocorneal incision with
      2 tiny conjunctival cuts at both ends and a clear corneal incision (CCI) in
      cataract surgery. SETTING: Department of Ophthalmology, Institute of Clinical
      Medicine, University of Tsukuba, Ibaraki, Japan. METHODS: Patients having routine
      cataract surgery were randomly divided into 2 groups based on incision type; that
      is, transconjunctival single-plane sclerocorneal or CCI. The incidence of
      intraoperative ballooning of the conjunctiva (chemosis) and the percentage of
      eyes that required stromal hydration to securely close the wound in each group
      were recorded and compared. RESULTS: Each group comprised 61 eyes (61 patients).
      No eye in the transconjunctival sclerocorneal group and 6 eyes (9.8%) in the CCI
      group developed intraoperative conjunctival chemosis (P = .027, Fisher exact
      probability test). Corneal stromal hydration was required in 2 eyes (3.3%) and 15
      eyes (24.6%), respectively (P = .001). CONCLUSION: The transconjunctival single
      plane sclerocorneal incision was effective and combined the merits of CCI
      incisions and sclerocorneal incisions.

PMID- 20692563
TI  - Visual outcomes after implantation of a refractive multifocal intraocular lens
      with a +3.00 D addition.
AB  - PURPOSE: To assess the visual outcomes after cataract surgery with implantation
      of a refractive multifocal intraocular lens (IOL) with a +3.00 D addition (add).
      SETTING: Centro Internacional de Microcirugia Ocular, Seville, Spain. METHODS:
      This prospective study evaluated visual outcomes after cataract surgery with
      implantation of a Rayner M-flex 630F +3 IOL over a 12-month follow-up. Monocular
      and binocular uncorrected and corrected distance, intermediate, and near visual
      acuities were recorded. Distance contrast sensitivity under photopic and mesopic
      conditions, subjective dysphotopic phenomena, and subjective spectacle dependence
      were assessed. RESULTS: The study enrolled 32 eyes of 22 patients. Twelve months
      postoperatively, the mean monocular corrected distance acuity was 0.03 +/- 0.05
      logMAR and the mean corrected near acuity was 0.04 +/- 0.05 logMAR. The binocular
      uncorrected and corrected near acuity was 0.25 +/- 0.08 logMAR and 0.03 +/- 0.02
      logMAR, respectively, at 6 months, with no changes thereafter. No patients
      reported dysphotopic phenomena at the 12-month visit. Of patients having
      binocular IOL implantation, 90% were spectacle independent for distance vision
      and 70% for near vision at 6 months. CONCLUSION: The refractive multifocal IOL
      with a +3.00 D add provided satisfactory visual outcomes through a full range of
      vision.

PMID- 20692564
TI  - Intraocular stability of an angle-supported phakic intraocular lens with changes
      in pupil diameter.
AB  - PURPOSE: To use anterior segment optical coherence tomography (AS-OCT) to
      evaluate the stability of a recently released angle-supported phakic intraocular
      lens (pIOL) in the anterior segment with changes in pupil diameter. SETTING:
      Keratoconus Unit, Vissum Corporation, Alicante, Spain. METHODS: In this
      observational cross-sectional study of consecutive eyes with moderate to high
      myopia, an AcrySof Cachet pIOL was implanted with the aim of minimizing the
      refractive error. An analysis of the position and stability of the pIOL before
      and after pharmacologic pupil dilation was performed 3 months postoperatively
      using the Visante AS-OCT system. A measurement protocol that included several
      anatomic parameters was developed and applied; the parameter values before and
      after dilation were compared. RESULTS: Twenty eyes of 20 patients ranging in age
      from 24 to 48 years old were evaluated. The anterior chamber depth increased
      significantly with pupil dilation (mean change 0.06 mm +/- 0.08 [SD]) (P<.01). A
      significant change was also observed in the distance between the center of the
      cornea at the endothelial plane and the anterior surface of the pIOL (mean change
      0.03 +/- 0.05 mm) (P = .01). The distances between the peripheral edges of the
      pIOL and the corneal endothelium and the distance between the crystalline lens
      and the pIOL did not change significantly (P>or=.14). CONCLUSION: The angle
      supported pIOL showed excellent intraocular behavior after pupil dilation, with
      no shortening of the distance between the pIOL and corneal endothelium at the
      center or peripheral edges of the pIOL.

PMID- 20692565
TI  - Rotational and centration stability of an aspheric intraocular lens with a
      simulated toric design.
AB  - PURPOSE: To assess the stability of the Akreos AO intraocular lens (IOL) platform
      with a simulated toric design using objective image analysis. SETTING: Six
      hospital eye clinics across Europe. METHODS: After implantation in 1 eye of
      patients, IOLs with orientation marks were imaged at 1 to 2 days, 7 to 14 days,
      30 to 60 days, and 120 to 180 days. The axis of rotation and IOL centration were
      objectively assessed using validated image analysis. RESULTS: The study enrolled
      107 patients with a mean age of 69.9 years +/- 7.7 (SD). The image quality was
      sufficient for IOL rotation analysis in 91% of eyes. The mean rotation between
      the first day postoperatively and 120 to 180 days was 1.93 +/- 2.33 degrees, with
      96% of IOLs rotating fewer than 5 degrees and 99% rotating fewer than 10 degrees.
      There was no significant rotation between visits and no clear bias in the
      direction of rotation. In 71% of eyes, the dilation and image quality was
      sufficient for image analysis of centration. The mean change in centration
      between 1 day and 120 to 180 days was 0.21 +/- 0.11 mm, with all IOLs decentering
      less than 0.5 mm. There was no significant decentration between visits and no
      clear bias in the direction of the decentration. CONCLUSION: Objective analysis
      of digital retroillumination images taken at different postoperative periods
      shows the aspheric IOL platform was stable in the eye and is therefore suitable
      for the application of a toric surface to correct corneal astigmatism.

PMID- 20692566
TI  - Reproducibility of intraocular lens decentration and tilt measurement using a
      clinical Purkinje meter.
AB  - PURPOSE: To determine the reproducibility of intraocular lens (IOL) decentration
      and tilt measurements with a new Purkinje meter instrument. SETTING: Moorfields
      Eye Hospital NHS Foundation Trust, London, United Kingdom. METHODS: After pupil
      dilation, images of pseudophakic eyes with a plate-style IOL (Akreos Adapt) were
      obtained using a recently developed Purkinje meter. Intraocular lens decentration
      and tilt were evaluated by analyzing the captured images using a semiobjective
      method by marking the reflexes in the images and automatic calculation using a
      dedicated software program. In study 1, examiner 1 examined the eyes first
      followed by examiner 2. Ten minutes later, examiner 1 performed a second
      measurement, after which the intraexaminer and interexaminer reproducibility were
      determined. In study 2, a Purkinje meter was used to measure pseudophakic eyes
      with slitlamp finding of clinical IOL decentration, IOL tilt, or both. The
      results were compared with retroillumination photographs and slitlamp findings.
      RESULTS: In study 1, there was high intraexaminer reproducibility for
      decentration (r = 0.95) and tilt (r = 0.85) and high interexaminer
      reproducibility for decentration (r = 0.84) and tilt (r = 0.75). In study 2, even
      in extreme cases of decentration and/or tilt, the Purkinje meter measurements
      were possible and appeared to correlate well with slitlamp findings. CONCLUSIONS:
      Acquisition of images in pseudophakic eyes with the Purkinje meter was simple and
      rapid. The method was highly reliable for 1 examiner and between 2 examiners.

PMID- 20692567
TI  - Ocular aberrations and visual performance with an aspheric single-piece
      intraocular lens: contralateral comparative study.
AB  - PURPOSE: To study spherical aberration, coma, and trefoil after implantation of a
      single-piece aspheric Tecnis intraocular lens (IOL) in cataract patients and the
      influence on photopic and mesopic contrast sensitivity. SETTING: Ophthalmology
      Department, Ain-Shams University Hospitals, Cairo, Egypt. METHODS: In this
      randomized prospective contralateral comparative study, patients had bilateral
      senile cataract. Eyes with a pathological condition other than cataract that
      might influence postoperative visual function were excluded. The aspheric IOL was
      compared with the Sensar AR40e spherical IOL. The IOL selection was randomized.
      Study criteria included corrected distance visual acuity (CDVA), wavefront
      aberrometry, and contrast visual acuity. RESULTS: Fifty-six eyes of 28 patients
      were enrolled. All patients completed the 2-month postoperative visit. There was
      no significant difference between the IOLs in CDVA (P>.05). Ocular spherical
      aberration was significantly lower with aspheric IOLs than spherical IOLs
      (P<.001). Two months after surgery, eyes with the aspheric IOL had better
      photopic contrast sensitivity and better mesopic contrast sensitivity at all
      cycles per degree. There was no significant difference in 3rd-order aberrations
      (coma and trefoil) between IOLs. CONCLUSIONS: After cataract surgery, the single
      piece aspheric IOL resulted in significantly lower ocular spherical aberration
      and significantly better mesopic contrast sensitivity. No significant difference
      in 3rd-order aberrations indicates that both IOLs had satisfactory centration in
      the capsular bag.

PMID- 20692568
TI  - Central corneal thickness measurements after myopic photorefractive keratectomy
      using Scheimpflug imaging, scanning-slit topography, and ultrasonic pachymetry.
AB  - PURPOSE: To compare central corneal thickness (CCT) measurements obtained with a
      dual Scheimpflug camera system (Galilei), a scanning-slit topographer (Orbscan
      II), and an ultrasound (US) pachymeter (SP-2000) after photorefractive
      keratectomy (PRK) for myopia. SETTING: Ophthalmic Research Center, Labbafinejad
      Medical Center, Tehran, Iran. METHODS: This prospective study enrolled patients
      who had PRK to correct myopia or myopic astigmatism and a postoperative follow-up
      of at least 5 months. The CCT was measured in a single session using Scheimpflug
      imaging, scanning-slit topography, and US pachymetry. Data were analyzed with
      paired t tests, linear regression, and Bland-Altman plots. RESULTS: The mean CCT
      in the 100 eyes (50 patients) was 524.06 microm +/- 38.56 (SD) with Scheimpflug
      imaging, 505.92 +/- 47.35 microm with scanning-slit topography, and 496.97 +/-
      42.74 microm with US pachymetry. The lower to upper 95% limits of agreement (LoA)
      with US pachymetry were 2.4 to 51.8 microm for Scheimpflug imaging and -22.2 to
      40.1 microm for scanning-slit topography. After application of a correction
      factor (0.95), the mean corrected Scheimpflug CCT measurement was 497.33 +/-
      36.59 microm and the lower to upper 95% LoA with US pachymetry were -25.9 to 25.5
      microm. The acoustic factor for scanning-slit topography was 0.94. CONCLUSIONS:
      The CCT measurements in eyes that had PRK were thicker with Scheimpflug imaging
      than with US pachymetry or scanning-slit topography in the late postoperative
      period. With application of a correction factor, the Scheimpflug measurements
      were closer to US pachymetry values and had better agreement than scanning-slit
      topography.

PMID- 20692569
TI  - Comparison of simulated keratometric changes induced by custom and conventional
      laser in situ keratomileusis after myopic ablation: retrospective chart review.
AB  - PURPOSE: To determine the relationship between the achieved refractive change and
      the change in simulated keratometry (K) after myopic laser situ keratomileusis
      (LASIK) and compare this relationship between custom and conventional treatments.
      SETTING: Department of Ophthalmology, University of California, Davis,
      Sacramento, California, and John A. Moran Eye Center, Salt Lake City, Utah, USA.
      METHODS: The change in simulated K and the refractive change induced by custom
      myopic LASIK and conventional LASIK were determined. The relationship between the
      variables was analyzed by regression methods. RESULTS: Custom treatment was
      performed in 106 eyes and conventional treatment in 224 eyes. Simple linear
      regression analysis did not fit the clinical observation when the refractive
      change was less than 2.00 diopters (D) of myopic correction with both treatments.
      Under the linear model and nonlinear model, each unit of refractive change
      yielded a greater change in corneal topographic power with custom treatment than
      with conventional treatment. With both treatments, the rate of change in
      simulated K was not constant and was much more variable with lower amounts of
      correction. The relationship was more constant and linear with larger amounts of
      refractive correction. CONCLUSIONS: The relationship between the measured change
      in simulated K and the induced refractive change better fit a nonlinear
      relationship with smaller amounts of refractive correction in custom LASIK and
      conventional LASIK. Under all forms of analysis, custom treatments yielded a
      greater per-unit change in corneal curvature than conventional treatments,
      especially for refractive corrections of 4.00 D and higher.

PMID- 20692570
TI  - Comparison of mechanical and femtosecond laser tunnel creation for intrastromal
      corneal ring segment implantation in keratoconus: prospective randomized clinical
      trial.
AB  - PURPOSE: To compare the outcomes of mechanical and femtosecond laser-assisted
      tunnel creation for intrastromal corneal ring segment (ICRS) implantation in eyes
      with keratoconus. SETTING: Kartal Training and Research Hospital, Istanbul,
      Turkey. METHODS: In this prospective study, consecutive eyes with keratoconus
      were randomly assigned to have ICRS tunnel creation with a mechanical device or a
      femtosecond laser. Keraring ICRS with a 5.0 mm diameter and 160-degree arc length
      were implanted in all cases. The uncorrected (UDVA) and corrected (CDVA) distance
      visual acuities, refraction, and keratometry (K) readings were measured
      preoperatively and 1 year postoperatively, and the data in the mechanical group
      and the femtosecond group were compared statistically. RESULTS: One year
      postoperatively, there was significant improvement in UDVA, CDVA, K readings,
      spherical equivalent (SE), and manifest sphere and cylinder in both groups
      (P<.05). The UDVA improved by 2.4 lines in the mechanical group and 2.0 lines in
      the femtosecond group and the CDVA by 3.3 lines and 2.7 lines, respectively; the
      mean reduction in maximum keratometry was 4.50 diopters (D) and 4.70 D,
      respectively, and the mean reduction in SE, 3.18 D and 3.09 D, respectively.
      There were no statistically significant differences between the 2 groups in
      visual or refractive results (P>.05). Anterior corneal perforation, superficial
      segment placement, and segment extrusion occurred in 1 eye each in the mechanical
      group. Segment migration occurred in 1 eye in the femtosecond group. CONCLUSION:
      Despite intraoperative complications in the mechanical group, the visual and
      refractive outcomes were similar to those in the femtosecond group.

PMID- 20692571
TI  - Modification and refinement of astigmatism in keratoconic eyes with intrastromal
      corneal ring segments.
AB  - PURPOSE: To analyze corneal astigmatic changes after implantation of intrastromal
      corneal ring segments (ICRS) in keratoconic eyes using the Alpins vectorial
      method. SETTING: Vissum Corporation, Alicante, Spain. METHODS: Keraring ICRS were
      implanted in eyes with a diagnosis of keratoconus. One of 3 surgeons performed
      the ICRS implantations using femtosecond technology and following the same
      protocol. Visual, refractive, keratometric, and corneal aberrometric changes were
      evaluated during a 12-month follow-up. Corneal astigmatic changes were also
      analyzed using the following Alpins vectorial components: targeted induced
      astigmatism (TIA), surgically induced astigmatism (SIA), difference vector,
      magnitude of error, flattening effect, and torque. RESULTS: Postoperatively,
      there was significant visual improvement (P = .03), significant central
      flattening (P = .03), and a significant reduction in manifest astigmatism
      (P<.01). The magnitude of SIA vector was significantly lower than the TIA
      postoperatively (P>or=.02). The mean magnitude of the difference vector 3 months
      postoperatively was +2.96 diopters (D) +/- 1.68 (SD). The mean magnitude of error
      remained negative and unchanged (P>or=.10). The mean magnitude of the flattening
      effect was significantly lower than the TIA at all postoperative visits
      (P<or=.01). The mean magnitude of torque vector was 1.21 +/- 0.98 D at 3 months.
      Significant negative correlations were found between preoperative corneal
      astigmatism and the magnitude of error and difference vector at all postoperative
      visits. CONCLUSION: Although ICRS implantation significantly reduced the
      magnitude of corneal astigmatism, there was a trend toward undercorrection and
      the meridian of correction was not appropriate in all cases, showing the need for
      nomogram adjustments.

PMID- 20692572
TI  - Surface roughness of intraocular lenses with different dioptric powers assessed
      by atomic force microscopy.
AB  - PURPOSE: To analyze the optic surface roughness and morphology of 2 types of
      hydrophobic acrylic intraocular lenses (IOLs) with various dioptric powers using
      atomic force microscopy (AFM). SETTING: Technical University of Cluj-Napoca,
      Faculty of Mechanics, Cluj-Napoca, Romania. METHODS: Atomic force microscopy was
      used to characterize the topography of 2 types of hydrophobic acrylic IOLs from a
      single manufacturer (SN60AT and SA30AL) with dioptric powers ranging from 10.0
      diopters (D) to 30.0 D. The AFM analysis was performed in contact mode using a V
      shaped silicon nitride cantilever with a pyramidal tip curvature of 15 nm and a
      nominal spring constant of 0.2 N/m. Detailed surface characterization of the IOL
      optic was obtained using 6 quantitative parameters provided by the AFM software.
      RESULTS: Five of 6 roughness parameters indicated statistically significant
      differences (P<.05) between IOLs with different dioptric powers, with the 10.0 D
      IOL in both models providing the smoothest optic surface. Between models with the
      same dioptric power, the SN60AT model had lower values of each surface roughness
      parameter than the SA30AL model. CONCLUSIONS: Atomic force microscopy was an
      accurate tool for assessing the surface properties of IOL optics. Manufacturing
      processes were responsible for introducing detectable differences in the
      topography of IOL biomaterials with identical copolymer constituents but
      different dioptric powers. Nanometric analysis may assist IOL manufacturers in
      developing IOLs with optimal surface characteristics.

PMID- 20692573
TI  - Corneal shaping and ablation of transparent media by femtosecond pulses in deep
      ultraviolet range.
AB  - PURPOSE: To assess the performance of a newly developed solid-state femtosecond
      ultraviolet (UV) laser system in corneal ablation. SETTING: Vilnius University,
      Laser Research Centre, Vilnius, Lithuania. METHODS: Femtosecond pulses in the
      deep UV range (205 nm) were obtained by the generation of the fifth-harmonic of
      an amplified Yb:KGW laser system (fundamental output at 1027 nm). Coupled with
      galvanometric beam-scanning mirrors, this system allowed ablation shaping of
      transparent media, including poly(methyl methacrylate) (PMMA), collagen, and ex
      vivo porcine corneas. The surfaces of ablated structures were characterized using
      a noncontact confocal optical profiler. RESULTS: Spherical structures were
      successfully formed in all 3 materials tested. A 10.0 diopter refraction change
      in the cornea was produced in 180 seconds. The resulting surface quality was
      significantly higher (roughness length >100 microm versus approximately 6 microm)
      in gelatin and ex vivo corneas than in PMMA. CONCLUSION: The solid-state
      femtosecond UV laser system seems an attractive alternative to the currently used
      ophthalmic argon-fluoride excimer laser system because of its small footprint,
      silent operation, and ability to generate femtosecond light pulses at both 1027
      nm (suitable for flap creation) and 205 nm (corneal ablation).

PMID- 20692574
TI  - Emerging antibiotic resistance in ocular infections and the role of
      fluoroquinolones.
AB  - Resistance to antibiotic agents is becoming increasingly prevalent among ocular
      infections. Between 19% and 60% of Streptococcus pneumoniae and Staphylococcus
      aureus isolates have been shown to be resistant to macrolide antibiotic agents,
      penicillin, and older fluoroquinolones. Although topical fluoroquinolones are
      considered first-line treatment of ocular infections, as much as 85% of
      methicillin-resistant S aureus isolates are resistant to ophthalmic
      fluoroquinolones, including the newer 8-methoxy fluoroquinolones, gatifloxacin
      and moxifloxacin. Besifloxacin, an 8-chlorofluoroquinolone, has a lower minimum
      inhibitory concentration against multidrug-resistant staphylococcal strains than
      other fluoroquinolones and less selective pressure for resistance development
      because of the lack of a systemic counterpart. In addition to the development of
      new antibacterial agents, antibiotic resistance in ocular infections may be
      reduced by following the same strategies used to minimize antimicrobial
      resistance in systemic infections.

PMID- 20692575
TI  - Visually significant haze after retreatment with photorefractive keratectomy with
      mitomycin-C following laser in situ keratomileusis.
AB  - Photorefractive keratectomy (PRK) with the adjunctive use of mitomycin-C (MMC)
      for the treatment of residual refractive error after laser in situ keratomileusis
      (LASIK) has been shown to be safe and effective, with no occurrences of visually
      significant postoperative haze reported. We report a case of visually significant
      haze after PRK with MMC for residual myopia following LASIK.

PMID- 20692576
TI  - Long-term follow-up of first-generation posterior chamber phakic intraocular
      lens.
AB  - We present a patient who received a first-generation posterior chamber phakic
      intraocular lens (PC pIOL) (Fyodorov IOL) to correct myopia 18 years previously.
      After a long lapse in the follow-up, the patient presented with a reduced
      endothelial cell count. Although the cataractogenic effect of first-generation PC
      pIOLs is well known, no sign of cataract was present. The patient was totally
      satisfied even after 18 years. To our knowledge, this is the first report of a
      long follow-up of a patient implanted with a first-generation PC pIOL.

PMID- 20692577
TI  - Clinicopathologic correlation of capsulorhexis phimosis with anterior flexing of
      single-piece hydrophilic acrylic intraocular lens haptics.
AB  - We describe 2 cases in which patients with 4-looped single-piece hydrophilic
      acrylic intraocular lenses (IOLs) exhibited postoperative complications including
      capsulorhexis phimosis, decentration, tilt, hyperopic shift, and luxation leading
      to explantation of the IOL-capsular bag complex. The excessive capsule fibrosis
      led to anterior flexing of the IOL haptics in both cases, even in the presence of
      a capsular tension ring (CTR). Histopathological analyses revealed a thick
      fibrocellular tissue attached to the inner surface of the anterior capsules,
      corresponding to the anterior capsule opacification and folds. An amorphous
      substance was observed on the outer surface of the anterior capsule in the case
      with a CTR, suggesting pseudoexfoliation material. These and similar cases raise
      concerns about the postoperative behavior of highly flexible IOLs in the presence
      of excessive capsular bag fibrosis. FINANCIAL DISCLOSURE: No author has a
      financial or proprietary interest in any material or method mentioned.

PMID- 20692578
TI  - Secondary pigment dispersion syndrome with single-piece acrylic IOL.

PMID- 20692579
TI  - Anterior capsular entrapment in an equatorial crack formed during injection of
      hydrophilic acrylic intraocular lens.

PMID- 20692582
TI  - September consultation: Refractive surgical problem.

PMID- 20692588
TI  - Differentiating transient and permanent negative dysphotopsia.

PMID- 20692590
TI  - Optical phenomena causing negative dysphotopsia.

PMID- 20692592
TI  - Comments on lift and crack technique for risky cataract cases.

PMID- 20692593
TI  - Negative dysphotopsia with spherical intraocular lenses.

PMID- 20692594
TI  - Lift and crack technique for phacoemulsification.

PMID- 20692597
TI  - Consensus statement on the adoption of the COPE guidelines.

PMID- 20692596
TI  - Usefulness of hydroimplantation technique for foldable IOL implantation.

PMID- 20692598
TI  - Micronutrients, wound healing, and prevention of pressure ulcers.

PMID- 20692599
TI  - Basics in nutrition and wound healing.
AB  - Wound healing is a process that can be divided into three different phases
      (inflammatory, proliferative, and maturation). Each is characterized by certain
      events that require specific components. However, wound healing is not always a
      linear process; it can progress forward and backward through the phases depending
      on various intrinsic and extrinsic factors. If the wound-healing process is
      affected negatively, this can result in chronic wounds. Chronic wounds demand
      many resources in the clinical daily routine. Therefore, local wound management
      and good documentation of the wound is essential for non-delayed wound healing
      and prevention of the development of chronic wounds. During the wound-healing
      process much energy is needed. The energy for the building of new cells is
      usually released from body energy stores and protein reserves. This can be very
      challenging for undernourished and malnourished patients. Malnutrition is very
      common in geriatric patients and patients in catabolic phases of stress such as
      after injury or surgery. For that reason a close survey of the nutritional status
      of patients is necessary to start supplementation quickly, if applicable. Wound
      healing is indeed a very complex process that deserves special notice. There are
      some approaches to develop guidelines but thus far no golden standard has
      evolved. Because wounds, especially chronic wounds, cause also an increasing
      economic burden, the development of guidelines should be advanced.

PMID- 20692600
TI  - Short-term specialized enteral diet fails to attenuate malnutrition impairment of
      experimental open wound acute healing.
AB  - OBJECTIVE: We assessed the effect of enteral refeeding on the morphology, gene
      expression, and contraction of acute open wounds in previously malnourished rats
      using two different enteral diets. METHODS: Adult male isogenic Lewis rats
      divided into two groups (eutrophic, n = 30; and previously malnourished, 12-15%
      body weight loss, n = 27) were subjected to cutaneous dorsal wounds and
      gastrostomy. Control rats received a standard oral diet (AIN-93M chow) plus
      enteral saline solution. Subject rats received chow plus a standard enteral diet
      or an enteral diet enriched with arginine and antioxidants. On post-trauma days 7
      and 14, wound granulation tissue samples were collected for morphologic analysis
      using hematoxylin and eosin and picrosirius stain or immunohistochemistry slides
      and real-time polymerase chain reaction for collagen I and III gene expression.
      Wound contraction was also evaluated by comparing wound images from days 0, 7,
      and 14. RESULTS: Malnourished control rats had increased intensity and duration
      of wound inflammation, impaired increase of fibroblast cells contingent on post
      trauma days 7 to 14, decreased expression of collagen III, and less wound
      contraction compared with eutrophic control rats. A specialized enteral diet did
      not improve wound healing of malnourished rats but did promote wound contraction
      at post-trauma day 7 in eutrophic rats. CONCLUSION: Short-term enteral refeeding,
      even with a specialized diet, failed to protect previously wounded malnourished
      rats from a prolonged inflammatory phase and impaired healing.

PMID- 20692601
TI  - Plasma albumin levels correlate with decreased microcirculation and the
      development of skin defects in hemodialyzed patients.
AB  - OBJECTIVES: Difficulty healing wounds and skin defects is a frequent problem in
      patients on chronic hemodialysis (HD) because of malnutrition, inflammation, and
      atherosclerosis (MIA) syndrome. The aim of the present study was to estimate the
      influence of peripheral blood flow changes during HD on the development of foot
      defects and its relationship to plasma albumin levels. METHODS: Peripheral skin
      blood flow was measured using a laser Doppler line scanner in 10 different areas
      of the dorsal part of the instep and the toes of each foot before and during HD
      with ultrafiltration (897 +/- 465 mL/procedure) in 31 HD patients (10 female, 21
      male; age 36-79 y, body mass index = 28 +/- 5.0). No skin defects or apparent
      acute disease or infection were detected in any patient at the time of laser
      Doppler line scanner measurement. The feet of the patients were clinically re
      examined carefully over the next 18 mo. RESULTS: We found a significant and
      constant decrease of skin blood flow during the HD procedure (P < 0.001). Skin
      blood flow was significantly correlated with serum albumin level both before HD
      (r = 0.36, P = 0.05) and during HD (r = 0.47, P = 0.007). Skin defects developed
      in 11 patients, with significantly lower skin blood flow during the 18-mo follow
      up period. A significantly larger number of patients who had normal perfusion
      remained defect-free in comparison to patients with critical perfusion (93%
      versus 38%, P = 0.002, Kaplan-Meier analysis). CONCLUSION: Skin blood flow may be
      impaired in HD patients. The apparent malnutrition and inflammation in HD
      patients are likely responsible for the decreased skin blood flow and the
      development of the difficulty to heal skin defects and wounds.

PMID- 20692602
TI  - Dietary effect of lactoferrin-enriched fermented milk on skin surface lipid and
      clinical improvement of acne vulgaris.
AB  - OBJECTIVE: Lactoferrin, a whey milk protein after removing precipitated casein,
      has a prominent activity against inflammation in vitro and systemic effects on
      various inflammatory diseases have been suggested. The objective was to determine
      dietary effects of lactoferrin-enriched fermented milk on patients with acne
      vulgaris, an inflammatory skin condition. METHODS: Patients 18 to 30 y of age
      were randomly assigned to ingest fermented milk with 200 mg of lactoferrin daily
      (n = 18, lactoferrin group) or fermented milk only (n = 18, placebo group) in a
      12-wk, double-blind, placebo-controlled study. Acne lesion counts and grade were
      assessed at monthly visits. The condition of the skin by hydration, sebum and pH,
      and skin surface lipids was assessed at baseline and 12 wk. RESULTS: Acne showed
      improvement in the lactoferrin group by significant decreases in inflammatory
      lesion count by 38.6%, total lesion count by 23.1%, and acne grade by 20.3%
      compared with the placebo group at 12 wk. Furthermore, sebum content in the
      lactoferrin group was decreased by 31.1% compared with the placebo group. The
      amount of total skin surface lipids decreased in both groups. However, of the
      major lipids, amounts of triacylglycerols and free fatty acids decreased in the
      lactoferrin group, whereas the amount of free fatty acids decreased only in the
      placebo group. The decreased amount of triacylglycerols in the lactoferrin group
      was significantly correlated with decreases in serum content, acne lesion counts,
      and acne grade. No alterations in skin hydration or pH were noted in either
      group. CONCLUSION: Lactoferrin-enriched fermented milk ameliorates acne vulgaris
      with a selective decrease of triacylglycerols in skin surface lipids.

PMID- 20692603
TI  - Skin wounds associated with calciphylaxis in end-stage renal disease patients on
      dialysis.
AB  - Calciphylaxis is a rare complication of chronic renal failure mostly with poor
      prognosis. Painful lesions on various skin surface areas are the most prominent
      feature of this serious disease. Subsequent infection of necrotic skin tissue is
      associated with the risk of sepsis. Pathophysiology is unclear, but several risk
      factors are known. The most important risk factor is impaired calcium-phosphate
      metabolism. Our paper describes two cases of different forms of calciphylaxis in
      patients with chronic renal failure. In the first case, pamidronate and
      cinacalcet were used for treatment. In the second described case, calciphylaxis
      was associated with secondary hyperparathyroidism and immediate subtotal
      parathyroidectomy was performed. Both patients were successfully treated, using
      systemic approach as well as dedicated local care for healing of skin wounds.

PMID- 20692604
TI  - Mosquito-specialist spiders.

PMID- 20692605
TI  - Spider monkeys.

PMID- 20692606
TI  - Spontaneous brain rhythms predict sleep stability in the face of noise.
AB  - Quality sleep is an essential part of health and well-being. Yet fractured sleep
      is disturbingly prevalent in our society, partly due to insults from a variety of
      noises [1]. Common experience suggests that this fragility of sleep is highly
      variable between people, but it is unclear what mechanisms drive these
      differences. Here we show that it is possible to predict an individual's ability
      to maintain sleep in the face of sound using spontaneous brain rhythms from
      electroencephalography (EEG). The sleep spindle is a thalamocortical rhythm
      manifested on the EEG as a brief 11-15 Hz oscillation and is thought to be
      capable of modulating the influence of external stimuli [2]. Its rate of
      occurrence, while variable across people, is stable across nights [3]. We found
      that individuals who generated more sleep spindles during a quiet night of sleep
      went on to exhibit higher tolerance for noise during a subsequent, noisy night of
      sleep. This result shows that the sleeping brain's spontaneous activity heralds
      individual resilience to disruptive stimuli. Our finding sets the stage for
      future studies that attempt to augment spindle production to enhance sleep
      continuity when confronted with noise.

PMID- 20692607
TI  - Mammalian herbivore breath alerts aphids to flee host plant.
AB  - Mammalian herbivores profoundly influence plant-dwelling insects [1]. Most
      studies have focused on the indirect effect of herbivory on insect populations
      via damage to the host plant [2,3]. Many insects, however, are in danger of being
      inadvertently ingested during herbivore feeding. Here, we report that pea aphids
      (Acyrthosiphon pisum) are able to sense the elevated heat and humidity of the
      breath of an approaching herbivore and thus salvage most of the colony by
      simultaneously dropping off the plant in large numbers immediately before the
      plant is eaten. Dropping entails the risk of losing the host plant and becoming
      desiccated or preyed upon on the ground [4,5], yet pea aphids may sporadically
      drop when threatened by insect enemies [6]. The immediate mass dropping, however,
      is an adaptation to the potential destructive impact of mammalian herbivory on
      the entire aphid colony. The combination of heat and humidity serves as a
      reliable cue to impending mammalian herbivory, enabling the aphids to avoid
      unnecessary dropping. No defensive behavior against incidental predation by
      herbivores has ever been demonstrated. The pea aphids' highly adaptive escape
      behavior uniquely demonstrates the strength of the selective pressure large
      mammalian herbivores impose on insect herbivores.

PMID- 20692608
TI  - Signal transduction: RABGEF1 fingers RAS for ubiquitination.
AB  - RAS proteins conduct signaling from surface receptors to cytoplasmic effectors,
      and RAS gain-of-function mutations are pervasive in cancer. A new mechanism for
      RAS signal attenuation with implications for receptor trafficking has been
      uncovered.

PMID- 20692609
TI  - Primatology: "a faithful friend is the medicine of life".
AB  - Close, stable social bonds enhance longevity in wild baboons, providing clues
      about the importance of social bonds in our own evolutionary history.

PMID- 20692610
TI  - Cell cycle: deconstructing tension.
AB  - Prior to anaphase, sister chromatids must be attached to microtubules and under
      tension, a condition that satisfies the spindle checkpoint. Removal of sister
      chromatid cohesion is predicted to cause a fall in tension. Two studies shed
      light on how cells avoid re-activation of the spindle checkpoint when cohesion is
      lost.

PMID- 20692611
TI  - Evolutionary genetics: desperate times call for more sex.
AB  - A new study has found that strains of the fungus Aspergillus nidulans produce
      more of their spores sexually in environments where they are less fit, resembling
      a hypothesized transitional stage in the evolution of sex.

PMID- 20692612
TI  - Animal cognition: multi-modal interactions in ant learning.
AB  - A recent study shows that desert ants use a precise behaviour, based on the
      internal cues of path integration, to facilitate the learning of visual landmark
      information. This raises fascinating questions about how insects encode familiar
      terrain.

PMID- 20692613
TI  - Axonal transport: CDKs as traffic signals for motor-ists along the axon?
AB  - A screen for axonal cargo mislocalization in Caenorhabditis elegans neurons
      implicates the cyclin-dependent kinases CDK-5 and PCT-1 and the cyclin CCY-1 in
      the regulation of the microtubule motor cytoplasmic dynein.

PMID- 20692614
TI  - Sensory learning: rapid extraction of meaning from noise.
AB  - Recent studies show that humans can rapidly learn to differentiate originally
      meaningless sounds into long-lasting memories, illustrating the flexibility of
      sensory processes and raising important questions about how sensory memories are
      formed.

PMID- 20692615
TI  - Visual consciousness: the binocular rivalry explosion.
AB  - A new behavioural technique solves a long-standing puzzle of binocular
      suppression, demonstrating that adapting reciprocal inhibition governs visual
      sensitivity and raising key questions about visual awareness.

PMID- 20692616
TI  - Cell polarity: keeping worms LeGaL.
AB  - The protein Lethal giant larvae (LGL) regulates cell polarity in diverse animal
      models. Now, an LGL orthologue has been identified in the worm Caenorhabditis
      elegans and is shown to function redundantly with a worm-specific polarity
      protein, PAR-2.

PMID- 20692617
TI  - Cytoskeletal cross-linking and bundling in motor-independent contraction.
AB  - Eukaryotic and prokaryotic cells use cytoskeletal proteins to regulate and modify
      cell shape. During cytokinesis or eukaryotic cell crawling, contractile forces
      are generated inside the cell to constrict the division site or to haul the rear
      of the cell forward, respectively. In many cases, these forces have been
      attributed to the activity of molecular motors, such as myosin II, which, by
      pulling on actin filaments, can produce contraction of the actin cytoskeleton.
      However, prokaryotic division is driven by the tubulin-like protein FtsZ and does
      not seem to require additional molecular motors to constrict the division site.
      Likewise, Dictyostelium discoideum and Saccharomyces cerevisiae can perform
      cytokinesis under motor-free conditions. In addition, many crawling cells can
      translocate when myosin is inhibited or absent. In this review, we point out
      another force-generation mechanism that can play a significant role in driving
      these processes in eukaryotes and prokaryotes. This mechanism is mediated by
      cross-linking and bundling proteins that form effective interactions between
      cytoskeletal filaments. Some recent studies in this area are reviewed and the
      physical underpinnings of this force-generation mechanism are explained.

PMID- 20692618
TI  - Comparative effectiveness research: what does it mean for imaging?

PMID- 20692619
TI  - Developing a new reference standard: is validation necessary?
AB  - RATIONALE AND OBJECTIVES: A gold standard is often an imperfect diagnostic test,
      falling short of achieving 100% accuracy in clinical practice. Using an imperfect
      gold standard without fully comprehending its limitations and biases can lead to
      erroneous classification of patients with and without disease. This will
      ultimately affect treatment decisions and patient outcomes. Therefore, validation
      is essential before implementing a reference standard into practice. Performing a
      comprehensive validation process is discussed, along with its advantages and
      challenges. The different types of validation methods are reviewed. An example
      from our work in developing a new reference standard for vasospasm diagnosis in
      aneurysmal subarachnoid hemorrhage patients is provided. CONCLUSION: Employing a
      new reference standard may result in a definitional shift of the disease and
      classification scheme of patients; therefore, it is important to also assess the
      impact of a new reference standard on patient outcomes and its clinical
      effectiveness.

PMID- 20692620
TI  - Multimodality computer-aided breast cancer diagnosis with FFDM and DCE-MRI.
AB  - RATIONALE AND OBJECTIVES: To investigate a multimodality computer-aided diagnosis
      (CAD) scheme that combines image information from full-field digital mammography
      (FFDM) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for
      computerized breast cancer classification. MATERIALS AND METHODS: From a
      retrospective FFDM database with 432 lesions (255 malignant, 177 benign) and a
      retrospective DCE-MRI database including 476 lesions (347 malignant, 129 benign),
      we constructed a multimodality dataset of 213 lesions (168 malignant, 45 benign).
      Each lesion was present on both FFDM and DCE-MRI images and deemed to be a
      difficult case given the necessity of having both clinical imaging exams. Using a
      manually indicated lesion location (ie, a seed point on FFDM images or a region
      of interest on DCE-MRI images, the computer automatically segmented the mass
      lesions and extracted lesion features). A subset of features was selected using
      linear stepwise feature selection and merged by a Bayesian artificial neural
      network to yield an estimate of the probability of malignancy. Receiver operating
      characteristic (ROC) analysis was used to evaluate the performance of the
      selected features in distinguishing between malignant and benign lesions.
      RESULTS: With leave-one-lesion-out cross-validation on the multimodality dataset,
      the mammography-only features yielded an area under the ROC curve (AUC) of 0.74
      +/- 0.04, and the DCE-MRI-only features yielded an AUC of 0.78 +/- 0.04. The
      combination of these two modalities, which included a spiculation feature from
      mammography and two kinetic features from DCE-MRI, yielded an AUC of 0.87 +/-
      0.03. The improvement of combining multimodality information was statistically
      significant as compared to the use of single modality information alone.
      CONCLUSIONS: A CAD scheme that combines features extracted from FFDM and DCE-MRI
      images may be advantageous to single-modality CAD in the task of differentiating
      between malignant and benign lesions.

PMID- 20692621
TI  - Correlation among on-call resident study volume, discrepancy rate, and turnaround
      time.
AB  - RATIONALE AND OBJECTIVES: With continued increase in imaging utilization and
      remote access image viewing technology, many academic radiology departments are
      presented with the suggestion to supplement on-call resident preliminary reports
      with an outsourced attending interpretation. This idea is often brought to
      administrative attention because of the subjective impression that outsourced
      studies will benefit from significantly faster interpretation times and lower
      discrepancy rates, especially when study volume is high. We attempt to
      retrospectively analyze on-call resident studies at a busy Trauma I university
      hospital and establish whether a statistical correlation exists among study
      volume, discrepancy rate, and turnaround time. MATERIALS AND METHODS: On-call
      computed tomography and ultrasound studies between January 2008 and June 2008
      were retrospectively reviewed by blinded staff radiologists for discrepancies
      between preliminary and final reports. A correlation analysis between discrepancy
      rate and study volume per shift was performed. In addition, correlation analysis
      between volume per shift and interpretation time was also performed. RESULTS: A
      total of 1133 studies were reviewed. The major discrepancy rate is 1.85% with
      average turnaround time of 28.5 minutes. The correlation coefficient between
      major discrepancy rate and study volume is 0.35. The correlation coefficient
      between interpretation time and study volume is 0.29. CONCLUSION: Our large
      retrospective review of preliminary reports from different residents reveals no
      significant correlation among discrepancy rate, turnaround time, and study
      volume. The overall discrepancy rate is similar to that reported by other
      studies. Other institutions can perform this study to analyze whether their
      volume and resident performance warrants supplemental assistance before depriving
      residents of the educational benefits the independent on-call experience affords.

PMID- 20692622
TI  - Medical education.

PMID- 20692623
TI  - 14-mile hike.

PMID- 20692624
TI  - Techniques to assess tissue oxygenation in the clinical setting.
AB  - The microcirculation plays an essential role in health and disease. Microvascular
      perfusion can be assessed directly using laser Doppler flowmetry and various
      imaging techniques or indirectly using regional capnometry and measurement of
      indicators of mismatch between oxygen delivery and oxygen consumption or indices
      of disturbed cellular oxygen utilization. Assessment of microvascular oxygen
      availability implies measurement of oxygen pressure or measurement of hemoglobin
      oxygen saturation. Microvascular function is assessed using other methods,
      including venous plethysmography. In this paper, I review current knowledge
      concerning assessment of the microcirculation with special emphasis on methods
      that could be used at the bedside.

PMID- 20692625
TI  - Chronic neonatal lung disease in 2010.

PMID- 20692627
TI  - The management of evolving bronchopulmonary dysplasia.
AB  - Bronchopulmonary dysplasia (BPD) is associated with increased mortality and
      significant long-term cardiorespiratory and neurodevelopmental sequelae.
      Treatment of evolving BPD in the neonatal intensive care unit (NICU) is
      challenging due to the complex interplay of contributing risk factors which
      include preterm birth per se, supplemental oxygen, positive pressure ventilation,
      patent ductus arterious, and pre- and postnatal infection. Management of evolving
      BPD requires a multimodal approach including adequate nutrition, careful fluid
      management, effective and safe pharmacotherapy, and respiratory support aiming at
      minimal lung injury. Among pharmacological interventions, caffeine has the best
      risk-benefit profile. Systemic postnatal corticosteroids should be reserved to
      ventilated infants at highest risk of BPD who cannot be weaned from the
      ventilator. Several ongoing randomised trials are evaluating optimal oxygen
      saturation targets in preterm infants. The most beneficial respiratory support
      strategy to minimise lung injury remains unclear and requires further
      investigation.

PMID- 20692626
TI  - Normal development of the lung and premature birth.
AB  - The following review focuses on the normal development of the lung from
      conception to birth. The defined periods of lung development-Embryonic,
      Pseudoglandular, Canalicular, Saccular and Alveolar-will be explored in detail in
      relation to gestational age. Cellular differentiation, formation of the
      conducting airways and respiratory zone and development of the alveoli will be
      reviewed. Pulmonary vascular development will also be examined within these
      periods to relate the formation of the blood-air barrier to the lungs for their
      essential function of gas exchange after birth. The development of the surfactant
      and cortisol systems will also be discussed as these need to be mature before the
      lungs are able to take on their role of respiration following birth. It is clear
      that premature birth interrupts normal lung development so the effect of preterm
      birth on lung development will be examined and the respiratory consequences of
      very preterm birth will be briefly explored.

PMID- 20692628
TI  - Pulmonary hypertension in chronic neonatal lung disease.
AB  - Pulmonary hypertension is an uncommon but significantly challenging complication
      of chronic neonatal lung disease [CNLD] as it occurs in the "new bronchopulmonary
      dysplasia [BPD]". The presence of pulmonary hypertension may be sub-clinical and
      is often overlooked as it is not considered in all but the more severe cases of
      children with CNLD. Whilst the mainstays of therapy are supplemental oxygen and
      time and the majority of children will have resolution of their pulmonary
      hypertension with lung growth, the advent of newer pharmacological treatments has
      offered stability and perhaps a better prognosis for more severe cases of
      pulmonary hypertension.

PMID- 20692629
TI  - Oxygen titration strategies in chronic neonatal lung disease.
AB  - The history of oxygen therapy in neonatology has been littered with error.
      Controversies remain in a number of areas of oxygen therapy, including targets
      and strategies in supplemental oxygen therapy in Chronic Neonatal Lung Disease
      (CNLD). This article reviews some of these controversies, and makes some
      recommendations based on the available evidence. In graduates of neonatal units
      who are left with CNLD, oxygen saturation should be kept above 93-95%, with
      levels below 90% being avoided as far as possible. Titration of oxygen should be
      done using oximetry recordings which include periods of different activities.
      Weaning of oxygen supplementation should only be done based on satisfactory
      recordings during a trial of a lower flow. There is insufficient evidence to say
      whether weaning for increasing hours a day or stepwise weaning to a continuous
      lower flow is a better method.

PMID- 20692630
TI  - What does imaging the chest tell us about bronchopulmonary dysplasia?
AB  - Bronchopulmonary dysplasia (BPD) is a common complication of preterm birth. Chest
      imaging is important in making the diagnosis of BPD, and in assessing for
      complications. More recently computerised tomography (CT) scanning has provided
      insights in to the pathophysiology of BPD. Studies in infants, young and school
      age children as well as young adults have consistently demonstrated abnormalities
      in the peripheral lung, possibly related either to small airway or alveolar
      disease. Advances in CT scanning may increase the clinical role for this
      modality, in addition newer techniques such as hyperpolarised gas magnetic
      resonance imaging are likely to provide further insights in to the nature of BPD
      and its effects on the developing lung.

PMID- 20692631
TI  - Acute lung injury in preterm newborn infants: mechanisms and management.
AB  - Respiratory morbidity and mortality remain common in preterm infants. The
      immature preterm lung is especially prone to injury. This process often starts in
      utero due to maternal chorioamnionitis, priming the lung for further injury in
      response to post-natal ventilation, oxygen and nosocomial infection. Pulmonary
      inflammation has been strongly implicated in the pathway leading to lung injury
      in this population of infants. Several therapeutic approaches have been attempted
      to prevent acute lung injury or to limit its progress. The mechanisms of acute
      lung injury in preterm infants; their clinical correlates and available
      therapeutic approaches are reviewed here.

PMID- 20692632
TI  - Acute lung injury in the child.
AB  - Acute lung injury(ALI) is an important condition in critically ill children,
      contributing to overall mortality and morbidity. ALI represents the severe
      spectrum of lower airways disease in children. It is the pathological culmination
      of diseases such as pneumonia and sepsis. These conditions elicit a host
      response, which results in a clinically and radiologically defined pulmonary
      syndrome, leading to additional physiological burden. Despite ALI being well
      described in the paediatric age group, its management has been largely based on
      adult studies. Ventilatory support with low tidal volumes, positive end
      expiratory pressure(PEEP) and permissive hypercapnoea are the pillars of
      management - derived from adult studies. For those caring for critically unwell
      children, this review outlines recent paediatric studies, current therapies in
      the context of available literature and novel emerging approaches.

PMID- 20692634
TI  - Paediatric asthma: everything that seemed to be certain no longer is.
AB  - 'Paediatric asthma: everything that seemed to be certain no longer is', holds the
      promise of leaving you with more questions than answers at the end of this review
      of paediatric asthma 2008-2009. This has often been true for asthma research, in
      particular over the past few years. Research with direct consequences for a
      clinician managing children with wheezing or asthma is discussed such as
      limitations in the characterisation of asthma phenotypes and the influence of
      early viral infections on asthma and the development of atopic sensitisation. It
      appears that wheezing in preschool children with specific viral pathogens confers
      differential rates of asthma risk. Viruses and day-care shift respiratory
      morbidity to an early age when it is more troublesome than at a later age but are
      not protective for sensitisation or asthma. What needs to be further explored is
      the relationship between viruses and recurrent wheeze or asthma in studies with
      stringently defined phenotypes including personal atopic status, timing of
      infection, and severity of infection. A modification of preschool wheeze
      phenotypes or replacement by other phenotypes that have been defined with the
      application of different methods is needed. Oral corticosteroids should not be
      prescribed in preschool children with acute mild to moderate viral wheeze, unless
      a severe outcome is anticipated or if the child has a classic atopic phenotype.
      Despite initial high expectations, FeNO was proven not to be beneficial for
      routine monitoring of asthma treatment.

PMID- 20692633
TI  - Early eradication of Pseudomonas aeruginosa in patients with cystic fibrosis.
AB  - Pseudomonas aeruginosa (Pa) is the predominant organism infecting the airways of
      patients with cystic fibrosis (CF). This organism has an armamentarium of
      survival mechanisms that allows it to survive in the CF airway. Since
      colonization and chronic infection with Pa is associated with poorer lung
      function and increased morbidity and mortality, therapies that can prevent
      infection could significantly improve the lives of patients with CF. Numerous
      studies have examined the effects of treatment on the eradication of Pa as a
      means to ameliorate disease. This article outlines the pathophysiology and
      clinical implication of Pa acquisition, and reviews the existing treatment
      regimens aimed at early eradication of Pa in patients with CF.

PMID- 20692635
TI  - Laparoscopic distal pancreatectomy with splenic preservation.

PMID- 20692636
TI  - The use of the Alvarado score in the management of right lower quadrant abdominal
      pain in the adult.
AB  - AIM OF THE STUDY: The Alvarado score is a validated test in clinical adult
      surgery practice which can be helpful in the diagnosis of acute appendicitis.
      This study aimed to assess the reliability and the reproducibility of this score
      for patients presenting in the emergency room with acute right lower quadrant
      abdominal pain. MATERIAL AND METHODS: A prospective monocenter study included all
      adults who presented in the emergency room with right lower quadrant abdominal
      pain. The score was calculated by assessing six symptoms and two laboratory
      values weighted by coefficients. The diagnosis of acute appendicitis was
      confirmed by the histological examination of the resected appendix. Three groups
      of patients with high, low, and intermediate scores were defined as described in
      the literature. RESULTS: Of the 233 patients studied, 174 underwent surgery:
      three had a normal appendix on histological exam. The statistical analysis of the
      results showed that a score lower than 4 was significantly associated with the
      absence of acute appendicitis while a score higher than 6 was significantly
      associated with acute appendicitis which required surgical care. But a score
      between 4 and 6 was not discriminant. CONCLUSION: The Alvarado score is a
      reliable, cheap and reproducible tool for the diagnosis of acute appendicitis in
      the emergency room; if the score is higher than 6 or lower than 4, there is no
      need for complementary exams. Patients with a score between 4 and 6, require
      serial reassessment of physical findings and score over 24 hours and/or
      complementary diagnostic exam such as ultrasound or CT scan.

PMID- 20692637
TI  - Latissimus dorsi free flap for reconstruction of extensive full-thickness
      abdominal wall defect. A case of desmoid tumor.
AB  - Desmoid tumor is a rare, benign fibroblastic tumor that is characterized by
      highly aggressive local invasiveness. The authors report the case of a 35-year
      old male who presented with a 20 cm para-umbilical tumor invading the right
      rectus abdominis muscle. This required a wide excision of the abdominal wall. The
      resulting defect was closed with a single-stage latissimus dorsi myocutaneous
      free flap in combination with a prosthetic mesh reconstruction. The authors
      discuss the therapeutic options for management of these rare tumors and the
      variety of available techniques for coverage and reconstruction after extensive
      parietal loss of substance.

PMID- 20692638
TI  - Reconstruction of a full-thickness abdominal wall defect using an anterolateral
      thigh free flap.
AB  - We present an original case of reconstruction of the abdominal wall after full
      thickness parietal resection using an anterolateral thigh flap harvested with its
      aponeurosis; we describe the advantages of this technique which has seldom been
      used for this indication. A 49-year-old male presented with a recurrent
      dermatofibrosarcoma protuberans involving the full thickness of the upper
      anterior abdominal wall; after excision, a 20 x 17 cm full-thickness defect was
      reconstructed with an omentoplasty, a bi-layered parietal prosthesis, and a
      fasciocutaneous free flap with its muscular aponeurosis from the anterolateral
      thigh. The postoperative course was uncomplicated. Functional and aesthetic
      results were satisfactory. There was no tumor recurrence or postoperative
      incisional hernia. Many reconstructive options have been proposed, but the
      anterolateral thigh free flap offers the advantage of an integral reconstruction
      of the abdominal wall without resultant donor site morbidity and with a
      satisfactory cosmetic result. In our hands, this flap is the ideal choice for
      reconstruction of the abdominal wall after loss of substance.

PMID- 20692639
TI  - The voice of self-control: blocking the inner voice increases impulsive
      responding.
AB  - Philosophers and psychologists have long-debated the notion that the voice in our
      heads might help us to control our actions. Evidence from a number of lines of
      research suggests that verbal resources help us to focus attention, providing
      reason to believe that the inner voice might aid self-control via this capacity.
      In this study we explored the link between verbal resources and self-control by
      occupying the inner voice and then assessing behavioral indices of self-control.
      Participants completed regular and switching versions of the Go/No-Go task while
      doing verbal or spatial secondary tasks. Compared with the spatial task, doing
      the verbal task resulted in more impulsive responding, as indicated by a greater
      tendency to make a 'Go' response, a pattern that was accentuated in the switching
      version of the Go/No-Go. Our results suggest that the inner voice helps us to
      exert self-control by enhancing our ability to restrain our impulses.

PMID- 20692640
TI  - A review of the feasibility of lightening structural polymeric composites with
      voids without compromising mechanical properties.
AB  - High performance polymer-fiber composites are high strength, low weight materials
      that have many applications, many of which would benefit from a decrease in
      weight, without a decrease in material properties. Generally, the fibers serve as
      the main load carriers, while the matrix serves to distribute load and protect
      the fibers from the environment. Thus, it is postulated that if the volume
      fraction of matrix is reduced, while still ensuring complete wetting of the
      fibers by the matrix, the per unit weight, i.e., specific, mechanical properties
      could be improved. This can be done by introducing small, spherical bubbles.
      Given the small average inter-fiber distance and assuming that the bubbles must
      not interact with the surface of the reinforcements the bubble diameter would
      need to be less than 1 MUm. Introducing bubbles this small and ensuring that they
      do not form, or become attached, on the surface of the reinforcement are
      significant challenges. Two methods to produce such bubbles and the effect of
      these bubbles on mechanical properties of neat resins are reviewed: the addition
      of hollow spherical fillers, called microballoons, and the creation of bubbles
      from blowing agents. Microballoons in resins are a class of materials called
      syntactic foams. Although commercial microballoons are too large, smaller
      diameters can be made and could be used to reduce the weight of a reinforced
      composite on the order of 10%. The use of a physical blowing agent to produce
      bubbles in a composite is also considered. However, traditional polymer foaming
      techniques may be inadequate, as nucleation on the reinforcing phase is likely,
      and the bubbles formed are generally too large, so the use of blowing agent wells
      is considered. Blowing agent wells are discontinuous regions made from copolymer
      micelles or immiscible polymers that act as reservoirs of blowing agent.
      Additionally, the use of nano-sized materials for use as heterogeneous nucleation
      sites and secondary reinforcement of the matrix is also considered. Bubbles made
      from blowing agent could reduce the weight slightly more than using hollow
      spheres, but the reduction would also be of the order of 10%.

PMID- 20692641
TI  - Plasma 25-hydroxyvitamin D levels in early-onset severe preeclampsia.
AB  - OBJECTIVE: Vitamin D deficiency has been linked to adverse pregnancy outcomes.
      The purpose of this investigation was to assess total 25-hydroxyvitamin D (25-OH
      D) levels at diagnosis of early-onset severe preeclampsia (EOSPE). STUDY DESIGN:
      After institutional review board approval, we enrolled subjects with EOSPE (<34
      weeks' gestation with severe preeclampsia) in this case-control investigation in
      a 1:2 ratio with gestation-matched, contemporaneous control subjects. Demographic
      and outcome information was collected for each subject. Plasma total 25-OH-D
      levels were determined by radioimmunoassay and reported in nanograms per
      milliliter. Results were analyzed by Mann-Whitney U and multivariable regression.
      RESULTS: Subjects with EOSPE (n = 50) were noted to have decreased total 25-OH-D
      levels relative to healthy control subjects (n = 100; P < .001). This difference
      in total 25-OH-D remained significant after control for potential confounders.
      CONCLUSION: Total 25-OH-D is decreased at diagnosis of EOSPE. Further study is
      needed to understand the impact of vitamin D deficiency on pregnancy outcomes.

PMID- 20692642
TI  - Isolation and characterization of true mesenchymal stem cells derived from human
      term decidua capable of multilineage differentiation into all 3 embryonic layers.
AB  - OBJECTIVE: The objective of the study was to isolate and characterize a
      population of mesenchymal stem cells (MSCs) from human term placental membranes.
      STUDY DESIGN: We isolated an adherent cell population from extraembryonic
      membranes. Morphology, phenotype, growth characteristics, karyotype, and
      immunological and differentiation properties were analyzed. RESULTS: The isolated
      placental MSCs were from maternal origin and named as decidua-derived mesenchymal
      stem cells (DMSCs). DMSCs differentiated into derivatives of all germ layers. It
      is the first report about placental MSC differentiation into alveolar type II
      cells. Clonally expanded DMSCs differentiated into all embryonic layers,
      including pulmonary cells. DMSCs showed higher life span than placental cells
      from fetal origin and proliferated without genomic instability. CONCLUSION: The
      data suggest that DMSCs are true multipotent MSCs, distinguishing them from other
      placental MSCs. DMSCs could be safely used in the mother as a potential source of
      MSCs for pelvic floor dysfunctions and immunological diseases. Additionally,
      frozen DMSCs can be stored for both autologous and allogeneic tissue
      regeneration.

PMID- 20692643
TI  - Topography-guided conductive keratoplasty: treatment for advanced keratoconus.
AB  - PURPOSE: To evaluate the use of topography-guided conductive keratoplasty in eyes
      with keratoconus. DESIGN: Interventional case series. METHODS: We examined 21
      eyes in 21 patients with advanced keratoconus. Topography-guided conductive
      keratoplasty was performed with intraoperative monitoring of corneal astigmatism
      using a surgical keratometer. Uncorrected visual acuity (UCVA), best spectacle
      corrected visual acuity (BSCVA), corneal topography, manifest refraction,
      intraocular pressure (IOP), corneal endothelial cell counts, complications, and
      eventual outcomes were evaluated. RESULTS: UCVA (logarithm of the minimal angle
      of resolution [logMAR]), which was 1.65 +/- 0.49 preoperatively, improved to 1.04
      +/- 0.64 at 1 week (P < .001) and 1.12 +/- 0.61 at 1 month after surgery (P <
      .001). BSCVA, which was 1.02 +/- 0.56 preoperatively, improved to 0.76 +/- 0.65
      at 1 week (P = .026) and 0.76 +/- 0.60 at 1 month after surgery (P = .003).
      Manifest refraction, which was -15.13 +/- 6.66 diopters (D) before surgery,
      declined to -9.97 +/- 6.71 D at 1 month after surgery (P = .002). Although
      corneal topography reverted to the preoperative pattern and UCVA and BSCVA also
      regressed toward preoperative values, 12 of 21 eyes were better able to tolerate
      and conduct normal daily activities using contact lenses. Five subjects have
      undergone or are considering corneal transplantation after unsatisfactory
      postoperative results. No serious perioperative complication was observed.
      CONCLUSIONS: Topography-guided conductive keratoplasty may be effective in
      reshaping corneal configuration in eyes with keratoconus, without serious
      complications, and possibly contributed to avoiding or delaying corneal
      transplantation.

PMID- 20692644
TI  - Changes in the lingual muscles of obese rats induced by high-fat diet feeding.
AB  - OBJECTIVE: To elucidate the influences of obesity on the properties and volume of
      lingual (genioglossus and geniohyoid) muscles in obese rats. METHODS: We analysed
      the accumulation of triacylglycerol and the diameter of myofibres in the lingual
      muscles using histochemistry, and the MyHC composition using real-time PCR in
      rats fed a high-fat diet for 10 weeks. In the genioglossus and geniohyoid
      muscles, the percentage of oil droplet areas in the obesity group were 3.6 and
      2.5 times greater than those in the control group, respectively (p<0.025). The
      diameters of the slow myofibres in the genioglossus and geniohyoid muscles were
      approximately 20% greater in the obesity group than in the control group
      (p<0.0001), while that of the fast myofibres in the geniohyoid muscle was
      approximately 10% greater in the obesity group than in the control group
      (p<0.0001). No significant difference in the expressions of any of the MyHC
      isoforms studied was found in any of the muscles studied between the obesity and
      control groups. CONCLUSION: High-fat diet feeding induced the fat deposition in
      the myofibre and influenced the structure of the lingual (genioglossus and
      geniohyoid) muscles.

PMID- 20692645
TI  - Can you feel the beat? Interoceptive awareness is an interactive function of
      anxiety- and depression-specific symptom dimensions.
AB  - Delineating the differential effects of anxiety versus depression on patterns of
      information processing has proved challenging. The tripartite model of mood
      disorders (Clark & Watson, 1991) suggests that one way forward is to adopt a
      dimensional rather than categorical approach, making it possible to explore the
      main and interaction effects of depression- and anxiety-specific symptoms on a
      given cognitive-affective process. Here we examined how the interplay of anxiety
      specific arousal and depression-specific anhedonia symptoms in the same
      individuals relate to interoceptive (bodily) awareness. 113 participants with
      varying levels of mood disorder symptoms completed a heartbeat perception task to
      assess interoceptive accuracy. Superior interoception was associated with anxiety
      specific arousal symptoms, and this relationship held when controlling for
      depression-specific anhedonia symptoms and shared general distress symptoms. This
      main effect was qualified by an interaction between anhedonia and arousal. As
      anhedonia symptoms increased in severity, the relationship between arousal and
      interoceptive accuracy became less strong. These results further validate the
      tripartite framework, help clarify the mixed existing literature on interoception
      in mood disorders, and suggest that considering the unique and interactive
      effects of different symptom dimensions is a useful strategy to help identify the
      cognitive-affective profiles associated with anxiety and depression.

PMID- 20692646
TI  - A meta-analysis of cytokines in Alzheimer's disease.
AB  - BACKGROUND: Studies suggest that inflammation is involved in the
      neurodegenerative cascade leading to Alzheimer's disease (AD) pathology and
      symptoms. This study sought to quantitatively summarize the clinical cytokine
      data. METHODS: Original English language peer-reviewed studies measuring cytokine
      concentrations in AD and healthy control subjects were included. Mean (+/-
      standard deviation) cytokine concentrations for AD and control subjects were
      extracted. RESULTS: Forty studies measuring peripheral blood cytokine
      concentrations and 14 measuring cerebrospinal fluid (CSF) cytokine concentrations
      were included. In peripheral blood, there were significantly higher
      concentrations (weighted mean difference [95% confidence interval]) of
      interleukin (IL)-6 (2.86 [1.68, 4.04] pg/mL, p < .00001, N[AD/control subjects] =
      985/680, 14 studies), tumor necrosis factor (TNF)-alpha (3.25 [.76, 5.74] pg/mL,
      p = .01, N = 680/447, 14 studies), IL-1beta (.55 [.32, .78] pg/mL, p < .00001, N
      = 574/370, 10 studies), transforming growth factor (TGF)-beta (67.23 [28.62,
      105.83] pg/mL, p = .0006, N = 190/158, 5 studies), IL-12 (7.60 [5.58, 9.62]
      pg/mL, p < .00001, N = 148/106, 5 studies), and IL-18 (15.82 [1.98, 29.66] pg/mL,
      p = .03, N = 131/94, 4 studies) but not of IL-4, IL-8, IL-10, interferon-gamma,
      or C-reactive protein in AD subjects compared with control subjects. There were
      significantly higher concentrations of TGF-beta (7.81 [2.27, 13.35] pg/mL, p
      =.006, N = 113/114, 5 studies) but not IL-6, TNF-alpha, and IL-1beta in the CSF
      of AD subjects compared with control subjects. CONCLUSIONS: These results
      strengthen the clinical evidence that AD is accompanied by an inflammatory
      response, particularly higher peripheral concentrations of IL-6, TNF-alpha, IL
      1beta, TGF-beta, IL-12 and IL-18 and higher CSF concentrations of TGF-beta.

PMID- 20692647
TI  - Aerobic exercise attenuates reinstatement of cocaine-seeking behavior and
      associated neuroadaptations in the prefrontal cortex.
AB  - BACKGROUND: Exercise has recently been suggested as an attractive alternative to
      pharmacotherapy for treating drug addiction. The goal of this study was to
      determine, using an animal model, whether aerobic exercise may block
      reinstatement of cocaine-seeking and its underlying neurobiology (i.e., neuronal
      signaling in the prefrontal cortex). METHODS: Following acquisition and 10 days
      of 24-hour access to cocaine (1.5 mg/kg/infusion) or saline under a discrete
      trial procedure (four infusions/hr), rats began a 14-day abstinence period.
      During this period, rats were either given access to a running-wheel for 2-hours
      each day or placed in similar boxes with the wheel locked. Cocaine-seeking was
      assessed following the 14th day of abstinence using a within-session
      extinction/cue-induced reinstatement procedure. Neuronal activity was assessed by
      examining phosphorylated levels of extracellular signal-regulated kinase (pERK)
      using Western blot analysis. RESULTS: Wheel running reduced cocaine-seeking
      during both extinction and reinstatement. Cocaine-seeking was positively
      associated with pERK levels in the prefrontal cortex. Although pERK levels were
      not different among saline controls, in the cocaine group, pERK levels were
      significantly decreased by exercise. CONCLUSIONS: Aerobic exercise may reduce
      relapse vulnerability by preventing the increase in cocaine-seeking and
      associated neuroadaptations in the prefrontal cortex that develop over an
      abstinence period.

PMID- 20692648
TI  - Reduced medial prefrontal cortex volume in adults reporting childhood emotional
      maltreatment.
AB  - BACKGROUND: Childhood emotional maltreatment (CEM) has been associated with a
      profound and enduring negative impact on behavioral and emotional functioning.
      Animal models have shown that adverse rearing conditions, such as maternal
      separation, can induce a cascade of long-term structural alterations in the
      brain, particularly in the hippocampus, amygdala, and prefrontal cortex. However,
      in humans, the neurobiological correlates of CEM are unknown. METHODS: Using high
      resolution T1-weighted 3T magnetic resonance imaging, anatomical scans and a
      whole-brain optimized voxel-based morphometry approach, we examined whether
      healthy control subjects and unmedicated patients with depression and/or anxiety
      disorders reporting CEM before age 16 (n = 84; age: mean = 38.7) displayed
      structural brain changes compared with control subjects and patients who reported
      no childhood abuse (n = 97; age: mean = 36.6). RESULTS: We found that self
      reported CEM is associated with a significant reduction in predominantly left
      dorsal medial prefrontal cortex volume, even in the absence of physical or sexual
      abuse during childhood. In addition, reduced medial prefrontal cortex in
      individuals reporting CEM is present in males and females, independent of
      concomitant psychopathology. CONCLUSIONS: In this study, we show that CEM is
      associated with profound reductions of medial prefrontal cortex volume,
      suggesting that sustained inhibition of growth or structural damage can occur
      after exposure to CEM. Given the important role of the medial prefrontal cortex
      in the regulation of emotional behavior, our finding might provide an important
      link in understanding the increased emotional sensitivity in individuals
      reporting CEM.

PMID- 20692649
TI  - Methylated anthocyanidin glycosides from flowers of Canna indica.
AB  - Methylated anthocyanin glycosides were isolated from red Canna indica flower and
      identified as malvidin 3-O-(6-O-acetyl-beta-d-glucopyranoside)-5-O-beta-d
      glucopyranoside (1), malvidin 3,5-O-beta-d-diglucopyranoside (2), cyanidin-3-O
      (6''-O-alpha-rhamnopyranosyl-beta-glucopyranoside (3), cyanidin-3-O-(6''-O-alpha
      rhamnopyranosyl)-beta-galactopyranoside (4), cyanidin-3-O-beta-glucopyranoside
      (5) and cyanidin-O-beta-galactopyranoside (6) by HPLC-PDA. Their structures were
      subsequently determined on the basis of spectroscopic analyses, that is, (1)H
      NMR, (13)C NMR, HMQC, HMBC, ESI-MS, and UV-vis. Compounds (1-4) were found to be
      in major quantity while compounds (5-6) were in minor quantity.

PMID- 20692650
TI  - Synthesis of new N-substituted 3,4,5-trihydroxypiperidin-2-ones from d-ribono-1,4
      lactone.
AB  - d-Ribono-1,4-lactone was treated with ethylamine in DMF to afford N-ethyl-d
      ribonamide 8a in quantitative yield. Using this reaction procedure, N-butyl, N
      hexyl, N-dodecyl, N-benzyl, N-(3-methyl-pyridinyl)-, N-(2-hydroxy-ethyl)-, and N
      (2-cyano-ethyl)-d-ribonamides 8b-h were obtained in quantitative yield.
      Bromination of the amides 8a-e with acetyl bromide in dioxane followed by
      acetylation gave 2,3,4-tri-O-acetyl-5-bromo-5-deoxy-N-ethyl, N-butyl, N-hexyl, N
      dodecyl, and N-benzyl-d-ribonamides 9a-e in 40-54% yields. To obtain 2,3,4-tri-O
      acetyl-5-bromo-5-deoxy-N-(3-methyl-pyridinyl)-, N-(2-hydroxy-ethyl)-, and N-(2
      cyano-ethyl)-9f-h, the bromination is necessary before the amidation reaction.
      Treatment of the bromoamides 9a-h with NaH in DMF followed by methanolysis
      affords N-alkyl-d-ribono-1,5-lactams 12a-h in quantitative yield.

PMID- 20692652
TI  - Structure of the O-polysaccharide of Cronobacter sakazakii O2 with a randomly O
      acetylated l-rhamnose residue.
AB  - Studies by sugar analysis and partial acid hydrolysis along with one- and two
      dimensional (1)H and (13)C NMR spectroscopy and high-resolution ESI MS showed
      that the O-polysaccharide (O-antigen) Cronobacter sakazakii ATCC 29004 (serotype
      O2) possesses a branched hexasaccharide O-unit with a randomly mono-O-acetylated
      terminal rhamnose residue in the side chain and the following structure:
      [Formula: see text]. A similar structure has been reported for the O
      polysaccharide of C. sakazakii 767, which differs in the presence of an
      additional lateral alpha-d-Glcp residue on GlcNAc and the pattern of O
      acetylation (Czerwicka, M., Forsythe, S. J.; Bychowska, A.; Dziadziuszko, H.;
      Kunikowska, D.; Stepnowski, P.; Kaczynski, Z. Carbohydr. Res.2010, 345, 908-913).

PMID- 20692651
TI  - Activation of glycosyl trichloroacetimidates with perchloric acid on silica
      (HClO(4)-SiO(2)) provides enhanced alpha-selectivity.
AB  - Obtaining high stereoselectivity in glycosylation reactions is often challenging
      in the absence of neighboring group participation. In this study, we demonstrate
      that activation of glycosyl trichloroacetimidate donors with immobilized
      perchloric acid on silica (HClO(4)-SiO(2)) provides higher alpha-selectivity than
      trimethylsilyl triflate (TMSOTf) for reactions that do not involve neighboring
      group participation.

PMID- 20692653
TI  - Synthesis of the 6-deoxytalose-containing tri- and hexasaccharides of the O
      antigen polysaccharide from Mesorhizobium huakuii IFO15243T.
AB  - The synthesis of a trisaccharide and a hexasaccharide, the monomer and dimer of
      the repeating unit of O-antigen polysaccharide from Mesorhizobium huakuii
      IFO15243, has been accomplished through suitable protecting group manipulations
      and stereoselective glycosylation reactions starting from commercially available
      l-rhamnose. The target oligosaccharides in the form of their p-methoxyphenyl
      glycosides are suitable for further glycoconjugate formation via selective
      cleavage of this group.

PMID- 20692654
TI  - Early expression of stem cell-associated genes within the CD8 compartment after
      treatment with a tumor vaccine.
AB  - Using a mouse neuroblastoma cell line, we have demonstrated that vaccination of
      tumor-free mice with a cell-based vaccine leads to productive immunity and
      resistance to tumor challenge, while vaccination of tumor-bearing mice does not.
      The T cell immunity induced by this vaccine, as measured by in vitro assays, is
      amplified by the depletion of Treg. Our goal is to understand this barrier to the
      development of protective cellular immunity. mRNA microarray analyses of CD8(+) T
      cells from naive or tumor-bearing mice undergoing vaccination were carried out
      with or without administering anti-CD25 antibody. Gene-expression pathway
      analysis revealed the presence of CD8(+) T cells expressing stem cell-associated
      genes early after induction of productive anti-tumor immunity in tumor-free mice,
      prior to any phenotypic changes, but not in tumor-bearing mice. These data
      demonstrate that early after the induction of productive immune response, cells
      within the CD8(+) T cell compartment adopt a stem cell-related genetic phenotype
      that correlates with increased anti-tumor function.

PMID- 20692655
TI  - Reading disorders and weak Verbal IQ following left hemisphere stroke in
      children: no evidence of compensation.
AB  - Children who suffer a left-hemisphere (LH) stroke do not appear to experience the
      verbal deficits that are apparent in adults with similar lesions. To explain
      these findings it has been suggested that the plasticity of the developing brain
      enables homologous areas in the right hemisphere (RH) to compensate for LH
      weakness. In this paper we find evidence against this theory from investigations
      into the effect of LH and RH lesions on intelligence and literacy skills in a
      group of children with unilateral postnatal stroke. At group level, there was no
      significant effect of LH stroke on Verbal IQ (VIQ) or upon reading ability, when
      compared with RH stroke. But at the individual level, the majority of children
      with LH stroke achieved standard scores below average, with some below -2 SD. The
      standard scores of children with RH lesions were normally distributed, showing no
      detrimental effect that would indicate compensation. Large discrepancies between
      VIQ and Performance IQ (PIQ), in both directions, were also a characteristic of
      the LH group. Using normative data that we collected on the reading of irregular
      and regular words and nonwords, we identified patterns of phonological and
      surface dyslexia in both lesioned groups. We argue that LH stroke reduces the
      efficiency of verbally-related skills, but that the processes available to
      children with postnatal lesions are those available to normally developing
      children, and that these can entail processes in either hemisphere.

PMID- 20692656
TI  - Determination of bromadiolone residues in fox faeces by LC/ESI-MS in relationship
      with toxicological data and clinical signs after repeated exposure.
AB  - In many countries, the fox (Vulpes vulpes), predator of small mammals, is
      particularly affected by anticoagulant rodenticides such as bromadiolone due to
      secondary poisoning. Nevertheless, to date, no method of exposure monitoring is
      applicable in the field over large areas, and no toxicological data are available
      concerning sensitivity of foxes to bromadiolone. The aim of this work was to
      compare excretion kinetics of bromadiolone in fox faeces with clinical and
      haemostatic effects after repeated exposure to intoxicated voles. A sensitive
      method for the quantification of bromadiolone excretion in fox faeces and plasma
      was developed, using liquid chromatography combined with electrospray ionisation
      mass spectrometry (LC/ESI-MS). The LoD was 0.9microg/kg and 0.15microg/L, and the
      LoQ was 3.0microg/kg and 0.5microg/L, in faeces and in plasma, respectively. Four
      captive foxes were fed for 2 or 5 days with water voles (Arvicola terrestris
      Sherman) spiked with bromadiolone at concentrations close to those measured in
      the field. Faeces and blood were collected for bromadiolone titration, and blood
      clotting tests were performed to monitor fox health daily during 10 days and then
      every 3-4 days until the end of the experiment (D28). Then, after euthanasia, a
      complete necropsy was performed, and levels of bromadiolone residues in the liver
      were determined. Bromadiolone residues were detected in faeces 15h after the
      first exposure. They increased dramatically during the exposure period and then
      gradually decreased, but they remained detectable at the end of the experiment,
      i.e., 26 days after the last exposure. Bromadiolone residues in plasma showed a
      similar pattern but were no longer detectable 7-24 days after the last exposure.
      Two foxes presented very severe external haemorrhages, requiring the
      administration of the antidote vitamin-K1. Bromadiolone residues in faeces and
      their relationships with exposure and other direct-markers that were measured are
      discussed. Liver residues and the toxicity data of our study will help to
      interpret data from fox carcasses collected by wildlife disease surveillance
      networks. These findings provide a basis for programs aiming to monitor the
      exposure of wild fox populations to bromadiolone using non-invasive methods based
      on standard sampling and analysis of residues in faeces.

PMID- 20692658
TI  - Processes underlying adherence to leg ulcer treatment: a qualitative field study.
AB  - BACKGROUND: Non-adherence to leg ulcer regimen is a major problem. Reasons for
      non-adherent behaviour are not fully understood. Literature about processes
      underlying adherence in leg ulcer patients is scarce. OBJECTIVES: To explore the
      processes underlying adherent behaviour in patients with leg ulcers who received
      an intervention to enhance adherence to leg ulcer lifestyle advice. DESIGN: A
      qualitative field study was conducted among patients receiving an adherence
      promoting intervention. SETTINGS: The study was carried out in a home care
      setting in Belgium. PARTICIPANTS: Twenty-six patients with venous leg ulcers were
      included and received the intervention from five tissue viability nurses in a
      community healthcare organisation. METHODS: Semi-structured interviews with open
      ended questions were held with patients and nurses after the end of the
      intervention. Data were also collected by means of participant observation. Data
      collection and data analysis took place iteratively and analysis was validated by
      means of researcher triangulation. RESULTS: Trust in the nurse was central to leg
      ulcer treatment adherence. Patients who had a trusting relationship with their
      nurse showed better adherence to the recommended lifestyle modifications. Trust
      was facilitated by nurses spending meaningful time with the patient, which means
      they took time to talk with the patient. Trust was also established because
      nurses provided care beyond patients' expectations, taking time for wound care
      and being attentive to pain and other problems. A trusting relationship promoted
      'compliance' even if patients were not convinced of the benefits of the leg ulcer
      lifestyle advice. Perceived physical improvement and diminished discomfort after
      following the lifestyle advice convinced patients of the importance and positive
      effect of the regimen, which they doubted at first. Self-efficacy for performing
      leg exercises was often much higher than self-efficacy for being physically
      active and elevating the legs. Physical impediments, co-morbidities and socio
      structural impediments influenced the patient's ability to adhere to leg ulcer
      advice. CONCLUSIONS: A conceptual framework to understand adherence to leg ulcer
      treatment was developed. Nurses should be aware of how nurse-related factors can
      affect adherence. Aspects that foster trust could be incorporated into leg ulcer
      care.

PMID- 20692659
TI  - The association of low selenium and renal insufficiency with coronary heart
      disease and all-cause mortality: NHANES III follow-up study.
AB  - Although prospective studies suggest that low selenium is a risk factor for
      cardiovascular disease, most clinical trials of selenium supplementation have not
      shown this benefit. Prospective studies of renal insufficiency show that it is
      associated with low-selenium levels, and increased cardiovascular disease risk.
      We hypothesized that low selenium and renal insufficiency might show biologically
      important interactions warranting a future trial of selenium supplementation in
      this high-risk group of patients with both renal insufficiency and low selenium.
      We evaluated the prospective association of low selenium and renal insufficiency
      with coronary heart disease and all-cause mortality. A cohort of 10,531 NHANES
      III participants aged 35 years or older with serum selenium measurements and
      creatinine were followed longitudinally and linked to the National Death Index.
      In multivariable-adjusted analysis, low-selenium levels were associated with an
      increased risk of CHD mortality (HR=1.26; 95% CI: 0.94-1.69) and an increased
      risk for all-cause mortality (HR=1.41; 95% CI: 1.18-1.68). Renal insufficiency
      was also associated with increased risk of CHD mortality (HR=1.64; 95% CI: 1.29
      2.08) and all-cause mortality (HR=1.51; 95% CI: 1.31-1.74). Despite the findings
      that adults with impaired renal function and low selenium had an increased risk
      for CHD mortality (HR=2.06; 95% CI: 1.13-3.75), there was no evidence of supra
      additivity between low selenium and renal insufficiency on rate of CHD mortality
      (relative excess risk due to the interaction [RERI=0.16; 95% CI: -1.34 to 1.65]
      or all-cause mortality (RERI=-0.85; 95% CI: -1.50 to -0.20). This analysis
      suggests that the combination of renal insufficiency and low selenium does not
      represent an extremely high-risk group where a randomized trial of selenium
      supplementation would be of greater value than focusing on all adults with low
      serum selenium.

PMID- 20692660
TI  - Research integrity and publication ethics.
AB  - The basic principle for professional conduct of science in all countries and all
      disciplines is honesty towards oneself and towards others. Therefore it is utmost
      important that the scientific community prevents scientific misconduct by
      fostering research integrity. This commentary reports on the experience of a
      German 'Ombudsman' and relates it to the international concepts of good
      scientific practice as well as the questions of publication ethics. Biomedical
      research seems to be most susceptible for scientific misconduct since
      internationally we see many of the cases in this field. Here possible
      explanations for the observed misconduct are discussed as well as ways to prevent
      it. The intention is to both alert scientists and ultimately to adjust the
      scientific system in a way which allows the next generation of scientists to
      develop their careers in true research integrity.

PMID- 20692661
TI  - Peculiarities of cell composition and cell proliferation in different type
      atherosclerotic lesions in carotid and coronary arteries.
AB  - Increased cell proliferation in early atherosclerotic lesions is recognized as an
      essential event in atherogenesis but the levels of cell proliferation in the
      different stages of atherosclerotic plague formation in different types of human
      large arteries are still insufficiently studied. In the present work, we studied
      intima thickness and proliferation of newly "infiltrated" hematogenous and
      resident cells in atherosclerotic lesions of the carotid and coronary arteries
      and compared these parameters with those in the aorta, which we reported in an
      earlier publication (Orekhov et al. [8]). Analysis of intima thickness and
      proliferation in grossly unaffected intima and in different types of
      atherosclerotic lesions (initial lesions, fatty streaks, lipofibrous plaques, and
      fibrous plaques) revealed that, although there were similar tendencies in the
      change of the infiltration levels of hematogenous cells and proliferation in
      different types of arteries, there were significant quantitative differences
      between different types of arteries. Hematogenous cells in lipofibrous plaques of
      the coronary and carotid arteries were found to account for a third and almost
      for a half of the total cell population, respectively, while atherosclerotic
      lesions in the aorta, as shown by us previously, contain no more than 15% of
      hematogenous cells. This suggests that the contribution of hematogenous cells to
      the development of atherosclerosis in the carotid and coronary arteries appears
      to be more significant than in the aorta. Despite the differences in the numbers
      of accumulating hematogenous cells in the intima, a similar "bell-shaped"
      dependence of cell numbers on the lesion type, involved the following sequence:
      unaffected intima--initial lesions--fatty streaks--lipofibrous plaques--fibrous
      plaques, was detected in the coronary and carotid arteries. The visualization of
      PCNA-positive cells in atherosclerotic and unaffected zones of the coronary and
      carotid arteries revealed similar patterns of the distribution of proliferating
      cells. The maximum numbers of PCNA-positive resident cells were identified in
      lipofibrous plaques. The changes in the total cell numbers were found to be
      accompanied by the changes in the numbers of both proliferating resident cells
      and proliferating hematogenous cells. According to our knowledge, this is the
      first report that provides factual data about the similarities and differences in
      cell composition and proliferation between different types of large arteries in
      which the development of atherosclerosis is of crucial importance.

PMID- 20692662
TI  - Quantitative CT imaging of the spatio-temporal distribution patterns of vasa
      vasorum in aortas of apoE-/-/LDL-/- double knockout mice.
AB  - OBJECTIVE: To investigate the distribution of vasa vasorum (VV) relative to
      advanced atherosclerotic lesions (calcified, fibrotic or hemorrhaged) along the
      aortic wall of apoE-/-/LDL-/- mice at the age of 25 and 80 weeks using high
      resolution nano-CT. METHODS: Aortas from male apoE-/-/LDL-/- mice at the age of
      25 weeks (n=4) and 80 weeks (n=7) were infused in situ with contrast agent and
      harvested for scanning with nano-CT. The spatial distribution of vasa vasorum
      [number and area/cross-section (mm2)] was compared to aortic luminal cross
      sectional area and plaque cross-sectional area in the ascending aorta, aortic
      arch and descending aorta. Results were complemented with co-localized histology.
      RESULTS: The number and total luminal cross-sectional area of VV showed a
      significant decrease in the ascending aorta and aortic arch from 25 to 80 weeks
      but not in the descending aorta. The number and cross-sectional area of VV showed
      significant local differences depending on whether it was near a fibrotic, and
      hemorrhaged or calcified plaque in animals at the age of 80 weeks. Area of VV
      progressively increased along the aorta from least in the ascending aorta<aortic
      arch<descending aorta in animals at the age of 80 weeks and is inverse in animals
      aged 25 weeks. CONCLUSION: Atherosclerotic lesion type is correlated to the
      number and cross-sectional area of VV in different aortic segments in apoE-/-/LDL
      /- mice. The chronological development of VV along the aorta proceeds distally
      from the ascending aorta and aortic arch.

PMID- 20692663
TI  - The effect of cement creep and cement fatigue damage on the micromechanics of the
      cement-bone interface.
AB  - The cement-bone interface provides fixation for the cement mantle within the
      bone. The cement-bone interface is affected by fatigue loading in terms of
      fatigue damage or microcracks and creep, both mostly in the cement. This study
      investigates how fatigue damage and cement creep separately affect the mechanical
      response of the cement-bone interface at various load levels in terms of plastic
      displacement and crack formation. Two FEA models were created, which were based
      on micro-computed tomography data of two physical cement-bone interface
      specimens. These models were subjected to tensile fatigue loads with four
      different magnitudes. Three deformation modes of the cement were considered:
      'only creep', 'only damage' or 'creep and damage'. The interfacial plastic
      deformation, the crack reduction as a result of creep and the interfacial
      stresses in the bone were monitored. The results demonstrate that, although some
      models failed early, the majority of plastic displacement was caused by fatigue
      damage, rather than cement creep. However, cement creep does decrease the crack
      formation in the cement up to 20%. Finally, while cement creep hardly influences
      the stress levels in the bone, fatigue damage of the cement considerably
      increases the stress levels in the bone. We conclude that at low load levels the
      plastic displacement is mainly caused by creep. At moderate to high load levels,
      however, the plastic displacement is dominated by fatigue damage and is hardly
      affected by creep, although creep reduced the number of cracks in moderate to
      high load region.

PMID- 20692664
TI  - Novel adsorbent based on multi-walled carbon nanotubes bonding on the external
      surface of porous silica gel particulates for trapping volatile organic
      compounds.
AB  - A novel adsorbent, 3-amino-propylsilica gel-multi-walled carbon nanotubes (APSG
      MW), was prepared by chemical bonding multi-walled carbon nanotubes on silica
      gel. The surface area of APSG-MW was 98 m(2)/g, and the particle size was between
      60 and 80 mesh with the average size of 215.0 microm. The adsorption capability
      of the new adsorbent to volatile organic compounds (VOCs) was measured. The
      effect of water to the adsorbent and its stability during storage were also
      investigated. Duplicate precision (DP) and distributed volume pair (DVP) on the
      basis of the EPA TO-17 criteria were estimated. The results showed that the
      sampling precision of the adsorbent was more superior compared to the MWCNTs
      because of the better air permeability. The new adsorbent was successfully
      applied in the determination of VOCs in ambient indoor air.

PMID- 20692665
TI  - Extraction of pesticides in water samples using vortex-assisted liquid-liquid
      microextraction.
AB  - A simple solvent microextraction method termed vortex-assisted liquid-liquid
      microextraction (VALLME) coupled with gas chromatography micro electron-capture
      detector (GC-microECD) has been developed and used for the pesticide residue
      analysis in water samples. In the VALLME method, aliquots of 30 microL toluene
      used as extraction solvent were directly injected into a 25 mL volumetric flask
      containing the water sample. The extraction solvent was dispersed into the water
      phase under vigorously shaking with the vortex. The parameters affecting the
      extraction efficiency of the proposed VALLME such as extraction solvent, vortex
      time, volumes of extraction solvent and salt addition were investigated. Under
      the optimum condition, enrichment factors (EFs) in a range of 835-1115 and limits
      of detection below 0.010 microg L(-1) were obtained for the determination of
      target pesticides in water. The calculated calibration curves provide high levels
      of linearity yielding correlation coefficients (r(2)) greater than 0.9958 with
      the concentration level ranged from 0.05 to 2.5 microg L(-1). Finally, the
      proposed method has been successfully applied to the determination of pesticides
      from real water samples and acceptable recoveries over the range of 72-106.3%
      were obtained.

PMID- 20692666
TI  - Determination of polyphenolic compounds by liquid chromatography-mass
      spectrometry in Thymus species.
AB  - Polyphenolic compounds represent a wide group of phytochemicals, including well
      known subgroups of phenolic acids, flavonoids, natural dyes, lignans etc., which
      are produced by plants. These natural bioactive compounds possess a variety of
      beneficial effects including antioxidant and anticarcinogenic activities,
      protection against coronary diseases as well as antimicrobial properties. Thymus
      species have already been reported as sources of different phenolic acids and
      flavonoids. Moreover, the composition and content of flavonoids in Thymus species
      play important role as taxonomic markers providing distinction of species. High
      performance liquid chromatography (HPLC) coupled with diode array detector (DAD)
      and on-line mass spectrometry (ESI-MS) method was used for analysis. The method
      was evaluated for a number of validation characteristics (repeatability and
      intermediate precision, LOD, LOQ, calibration range, and recovery). The
      polyphenolic pattern of five native Hungarian Thymus species (T. glabrescens
      Willd., T. pannonicus All., T. praecox Opiz, T. pulegioides L., and T. serpyllum
      L.) was characterized. The dominant compound was rosmarinic acid, which ranged
      between 83.49 MUg g(-1) and 1.436 mg g(-1). Other phenolic acids (ferulic acid,
      caffeic acid and its other derivatives, chlorogenic acid and p-coumaric acids)
      were present in every examined Thymus species, as well as flavanones: naringenin,
      eriodictyol and dihydroquercetin; flavones: apigenin and apigenin-7-glucoside,
      flavonols: quercetin and rutin. The polyphenolic pattern was found to be a useful
      additional chemotaxonomic tool for classification purposes and determination of
      the locality of origin.

PMID- 20692667
TI  - Properties of subcritical water as an eluent for reversed-phase liquid
      chromatography--disruption of the hydrogen-bond network at elevated temperature
      and its consequences.
AB  - The use of subcritical water as an eluent for reversed-phase liquid
      chromatography is further explored. Shape selectivity as well as thermodynamic
      values for solute transfer were measured and compared to those seen with
      traditional ambient methanol/water and acetonitrile/water mobile phases. Linear
      solvation energy analysis was also used to analyze extrapolated values of the
      retention factor in pure water at ambient temperatures (k'w) for subcritical
      water and ambient hydroorganic mobile phases. Results indicate that it is likely
      that a large disruption in the hydrogen-bonding network of water at high
      temperatures causes unique chromatographic selectivity, as well as prohibits
      accurate extrapolation from high temperature to ambient conditions using pure
      water. Additionally, subcritical water was not found to be a suitable mobile
      phase for determining k'w for use in estimating octanol/water partition
      coefficients.

PMID- 20692668
TI  - Simultaneous determination of positive and negative pharmaceutical counterions
      using mixed-mode chromatography coupled with charged aerosol detector.
AB  - A mixed-mode chromatography coupled with charged aerosol detector (CAD) method
      was developed in this work to simultaneously determine pharmaceutical counterions
      including both inorganic ions and organic ions in the forms of cations and
      anions. 25 commonly used pharmaceutical ions were studied and simultaneously
      separated within 20 min by this single method. A silica based mixed-mode column
      with reversed-phase/cation-exchange/anion-exchange modes was used. It provides
      reversed-phase, strong cation-exchange and weak anion-exchange properties at the
      same time. It also provides the HILIC behavior at high percentage of organic
      solvent. The effects of mobile-phase organic strength, buffer ions, ionic
      strength, pH and column temperature have been investigated to optimize the method
      as well as to understand the retention and separation mechanisms. Conventional
      HPLC system was used and no special chromatography system is needed. The
      presented method has been employed successfully for screening and quantitative
      analysis of counterions, unknown ionic impurities and salts in active
      pharmaceutical ingredients and in process control samples with excellent
      accuracy, precision and sensitivity. This method provides a simple, fast and
      generic approach to speed up pharmaceutical research and development process and
      enhance lab efficiency. The similar methodologies can be applied to other ion
      analysis.

PMID- 20692669
TI  - Hydrothermal synthesis of high-quality type-II CdTe/CdSe quantum dots with near
      infrared fluorescence.
AB  - A simple hydrothermal method is developed for the synthesis of high-quality,
      water-soluble, and near-infrared (NIR)-emitting type-II core/shell CdTe/CdSe
      quantum dots (QDs) by employing thiol-capped CdTe QDs as core templates and
      CdCl(2) and Na(2)SeO(3) as shell precursors. Compared with the original CdTe core
      QDs, the core/shell CdTe/CdSe QDs exhibit an obvious red-shifted emission, whose
      color can be tuned between visible and NIR regions (620-740 nm) by controlling
      the thickness of the CdSe shell. The photoluminescence quantum yield (PL QY) of
      CdTe/CdSe QDs with an optimized thickness of the CdSe shell can reach up to 44.2%
      without any post-preparative treatment. Through a thorough study of the
      core/shell structure by high-resolution transmission electron microscopy (HRTEM),
      ultraviolet-visible (UV-vis) absorption spectra, fluorescence spectra, X-ray
      powder diffraction (XRD) and X-ray photoelectron spectroscopy (XPS), the as
      prepared CdTe/CdSe QDs demonstrate good monodispersity, hardened lattice
      structure and excellent photostability, offering a great potential for biological
      application.

PMID- 20692670
TI  - Electrospun nanofibers of V-doped TiO2 with high photocatalytic activity.
AB  - In this work, V-doped TiO(2) nanofibers with different V contents have been
      fabricated by an electrospinning technique. The as-prepared nanofibers were
      characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD),
      Raman spectra, X-ray photoelectron spectroscopy (XPS), and UV-Vis diffuse
      reflectance (DR) spectroscopy. The results indicated that the V(4+) or V(5+) ions
      were successfully incorporated into the crystal lattice of anatase TiO(2)
      nanofibers. Meanwhile, the V doping could extend the visible light absorption of
      TiO(2) nanofibers. The photocatalytic experiments indicated that the obtained V
      doped TiO(2) nanofibers possessed high activity for the photodegradation of
      organic pollutant methylene blue (MB). Especially, the 1.0 and 5.0 wt.% V-doped
      TiO(2) nanofibers exhibited the best catalytic activity under visible and
      ultraviolet (UV) light irradiation, respectively. Also, these nanofibers could be
      easily recycled without a decrease of the photocatalytic activity.

PMID- 20692671
TI  - Drying of colloidal droplets on superhydrophobic surfaces.
AB  - Recent research on the flow patterns during the drying of droplets of solutions
      or suspensions has revealed a characteristic flow of dissolved or suspended
      material to the droplet periphery to produce the 'coffee ring' phenomenon. This
      effect was used to make ceramic well-plates by spontaneous manufacturing. Here we
      demonstrate that when a colloidal droplet dries on a superhydrophobic surface,
      the effect is rather different. Evaporation from the region adjacent to the three
      phase line becomes so restricted that the interior flows, and hence the final
      destination of particles, changes and the characteristic bowl-shape becomes
      inverted.

PMID- 20692672
TI  - Carbon nanotube/raspberry hollow Pd nanosphere hybrids for methanol, ethanol, and
      formic acid electro-oxidation in alkaline media.
AB  - In this paper, raspberry hollow Pd nanospheres (HPNs)-decorated carbon nanotube
      (CNT) was developed for electro-oxidation of methanol, ethanol, and formic acid
      in alkaline media. The electrocatalyst was fabricated simply by attaching HPNs
      onto the surface of CNT which had been functionalized by polymer wrapping. The as
      prepared HPN-CNTs (CHPNs) were characterized by transmission electron microscopy
      (TEM), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy
      (EDX), and X-ray photoelectron spectroscopy (XPS). The increasing interest and
      intensive research on fuel cell inspire us to investigate the electrocatalytic
      properties of the prepared nanostructures. Besides that, previous reports about
      alkaline other than acidic media could supply a more active environment guide us
      to examine the electrocatalytic properties in alkaline electrolyte. It is found
      that this novel hybrid electrocatalyst exhibits excellent electrocatalytic
      properties and can be further applied in fuel cells, catalysts, and sensors.

PMID- 20692673
TI  - Recurrent Hopkin's syndrome: a case report and review of the literature.
AB  - Flaccid paralysis affecting one or more limbs after an asthma attack is a
      poliomyelitis-like illness known as Hopkins' syndrome (HS). Although a viral
      infection or multifactorial immune suppression during an acute attack of
      bronchial asthma has been proposed to be the mechanism involved in this syndrome,
      the precise etiopathogenetic mechanism remains unknown. We report a 13-year-old
      girl who had recurrent acute episodes of myelitis after asthma attacks. She had
      four episodes of acute flaccid paralysis, each of which was preceded by acute
      asthma attacks. Some of the attacks were accompanied by sensory and sphincter
      disturbances. She had hyperIgEaemia and the prick test to Dermatophagoides
      farinae and cedar pollen was strongly positive. The present case is the first HS
      case demonstrating frequent recurrences and suggests a possible link between HS
      and atopic myelitis.

PMID- 20692674
TI  - [Central neurocytoma: Study of 32 cases and review of the literature].
AB  - Central neurocytoma is a rare benign neoplasm of the central nervous system. The
      intraventricular location close to the Monro foramina and the attachment to the
      septum pellucidum are characteristic for the diagnosis. However, atypical
      appearances may be encountered and confused with other neoplasms. The authors
      report the radiological findings of 32 surgically treated and pathologically
      confirmed neurocytomas.

PMID- 20692675
TI  - Propagation of elastic waves in an anisotropic functionally graded hollow
      cylinder in vacuum.
AB  - As a non-destructive, non-invasive and non-ionizing evaluation technique for
      heterogeneous media, the ultrasonic method is of major interest in industrial
      applications but especially in biomedical fields. Among the unidirectionally
      heterogeneous media, the continuously varying media are a particular but
      widespread case in natural materials. The first studies on laterally varying
      media were carried out by geophysicists on the Ocean, the atmosphere or the
      Earth, but the teeth, the bone, the shells and the insects wings are also
      functionally graded media. Some of them can be modeled as planar structures but a
      lot of them are curved media and need to be modeled as cylinders instead of
      plates. The present paper investigates the influence of the tubular geometry of a
      waveguide on the propagation of elastic waves. In this paper, the studied
      structure is an anisotropic hollow cylinder with elastic properties (stiffness
      coefficients c(ij) and mass density rho) functionally varying in the radial
      direction. An original method is proposed to find the eigenmodes of this
      waveguide without using a multilayered model for the cylinder. This method is
      based on the sextic Stroh's formalism and an analytical solution, the matricant,
      explicitly expressed under the Peano series expansion form. This approach has
      already been validated for the study of an anisotropic laterally-graded plate
      (Baron et al., 2007; Baron and Naili, 2010) [6,5]. The dispersion curves obtained
      for the radially-graded cylinder are compared to the dispersion curves of a
      corresponding laterally-graded plate to evaluate the influence of the curvature.
      Preliminary results are presented for a tube of bone in vacuum modelling the in
      vitro conditions of bone strength evaluation.

PMID- 20692676
TI  - Induction of interferon-stimulated genes by Simian virus 40 T antigens.
AB  - Simian virus 40 (SV40) large T antigen (TAg) is a multifunctional oncoprotein
      essential for productive viral infection and for cellular transformation. We have
      used microarray analysis to examine the global changes in cellular gene
      expression induced by wild-type T antigen (TAg(wt)) and TAg-mutants in mouse
      embryo fibroblasts (MEFs). The expression profile of approximately 800 cellular
      genes was altered by TAg(wt) and a truncated TAg (TAg(N136)), including many
      genes that influence cell cycle, DNA-replication, transcription, chromatin
      structure and DNA repair. Unexpectedly, we found a significant number of immune
      response genes upregulated by TAg(wt) including many interferon-stimulated genes
      (ISGs) such as ISG56, OAS, Rsad2, Ifi27 and Mx1. Additionally, we also observed
      activation of STAT1 by TAg(wt). Our genetic studies using several TAg-mutants
      reveal an unexplored function of TAg and indicate that the LXCXE motif and p53
      binding are required for the upregulation of ISGs.

PMID- 20692677
TI  - Comparative transcriptomics of the response of Escherichia coli to the
      disinfectant monochloramine and to growth conditions inducing monochloramine
      resistance.
AB  - Escherichia coli growth in biofilms and growth at a suboptimal temperature of 20 
      degrees C have been shown to decrease sensitivity to monochloramine (Berry, D.,
      C. Xi, L. Raskin. 2009. Environ. Sci. Technol. 43, 884-889). In order to better
      understand why growth conditions affect sensitivity to monochloramine, a
      comparative transcriptomic approach was used to identify common patterns of
      differentially-expressed genes under these growth conditions and during
      monochloramine exposure. This approach revealed a set of differentially-expressed
      genes shared under multiple conditions (planktonic growth at 20  degrees C,
      biofilm growth, and exposure of planktonic cells to monochloramine), with nine
      genes shared under all three conditions. Functional gene categories enriched in
      the shared gene sets included: general metabolic inhibition, redox and
      oxidoreductase response, cell envelope integrity response, control of iron and
      sulfur transport metabolism and several genes of unknown function. Single gene
      deletion mutant analyses verified that loss of 15 of the 24 genes up-regulated
      during monochloramine exposure as well as during other tested conditions
      increased E. coli sensitivity to monochloramine up to two fold. Constitutive
      expression of down-regulated genes in single gene mutants yielded mixed results,
      indicating that the expression of some down-regulated genes actually decreases
      sensitivity to monochloramine. These results contribute to the understanding of
      the bacterial response to disinfectants by characterizing the overlap between
      growth condition associated stress responses and monochloramine-associated stress
      responses. This characterization highlights the bacterial responses responsible
      for decreased sensitivity to monochloramine under different growth conditions.

PMID- 20692678
TI  - Kinetics of inactivation of indicator pathogens during thermophilic anaerobic
      digestion.
AB  - Thermophilic anaerobic sludge digestion is a promising process to divert waste to
      beneficial use, but an important question is the required temperature and holding
      time to achieve a given degree of pathogen inactivation. In this study, the
      kinetics of inactivation of Ascaris suum and vaccine strain poliovirus type 1
      (PVS-1), selected as indicators for helminth ova and enteric viruses
      respectively, were determined during anaerobic digestion at temperatures ranging
      from 51 to 56  degrees C. Inactivation of both indicator organisms was fast with
      greater than two log reductions achieved within 2 h for A. suum and three log
      reductions for PVS-1, suggesting that the current U.S. regulations are largely
      conservative. The first-order inactivation rate constants k followed Arrhenius
      relationship with activation energies of 105 and 39 KJ mol(-1) for A. suum and
      PVS-1, respectively indicating that A. suum was more sensitive to temperature.
      Although inactivation was fast, the presence of compounds in the sludge that are
      known to be protective of pathogen inactivation was observed, suggesting that
      composition-dependent time-temperature relationships are necessary.

PMID- 20692679
TI  - Bacterial community dynamics in horizontal flow constructed wetlands with
      different plants for high salinity industrial wastewater polishing.
AB  - This study is focused on the diversity of bacterial communities from two series
      of horizontal subsurface flow constructed wetlands (CW) polishing high salinity
      tannery wastewater. Each series was planted with Arundo donax or Sarcocornia sp.
      in a substrate composed by expanded clay and sand. Chemical and biochemical
      oxygen demand removal efficiencies were similar in each series, varying between
      58 and 67% (inlet COD 218 +/- 28 mg L(-1)) and 60 and 77% (inlet BOD(5) 37 +/- 6
      mg L(-1)), respectively. High numbers of culturable bacteria were obtained from
      substrate and root samples - 5.75 * 10(6)-3.95 * 10(8) CFU g(-1) recovered on
      marine agar and 1.72 * 10(7)-8.46 * 10(8) CFU g(-1) on nutrient agar. Fifty
      bacterial isolates were retrieved from the CW, related phylogenetically to
      Firmicutes, Actinobacteria, Bacteroidetes, alpha-, beta-, and gamma
      Proteobacteria. Changes in the bacterial communities, from roots and substrate of
      each series, related to the plant species, hydraulic loading rates and along CW
      operation were examined using denaturating gradient gel electrophoresis (DGGE).
      The clustering analysis suggested that a diverse and distinct bacterial community
      inhabits each series, which was related to the type of plant present in each CW.

PMID- 20692680
TI  - State indicators for monitoring the anaerobic digestion process.
AB  - Anaerobic process state indicators were used to monitor a manure digester exposed
      to different types of disturbances, in order to find the most proper indicator(s)
      for monitoring the biogas process. Online indicators tested were biogas
      production, pH, volatile fatty acids (VFA), and dissolved hydrogen. Offline
      indicators tested were methane and hydrogen content in the biogas. A CSTR reactor
      with 7.2 L working volume was operated at a varying hydraulic loading rate (HRT
      10-20 days) for 200 days. During this period, the reactor was overloaded with
      extra organic matter such as glucose, lipid, gelatine, and bio-fibers, in order
      to create dynamic changes in the process state. Biogas production increased in
      response to the increase in organic load with a slight decrease in methane
      content. pH was relatively stable and did not show clear response to hydraulic
      load changes. However, pH changes were observed in response to extra organic
      load. Individual VFA concentrations were an effective indicator, with propionate
      persistent for the longest time after introduction of the disturbance. Dissolved
      hydrogen was very sensitive to the addition of easily degradable organics.
      However, it responded also to other disturbances such as slight air exposure
      which had no impact on process performance. A combination of acetate, propionate
      and biogas production is an effective combination to monitor this type of
      digesters effectively.

PMID- 20692681
TI  - Offensive odorants released from stormwater catch basins (SCB) in an urban area.
AB  - The potent role of stormwater catch basins (SCB) as a source of malodor in urban
      areas has been recognized because of its active involvement in the production and
      release of diverse odorants. Here, the status of odor pollution was investigated
      from two types of SCBs (i.e., wet and dry systems) by measuring a list of
      offensive odorants (i.e., reduced sulfur compounds (RSC), carbonyl compounds,
      nitrogenous, volatile organic compounds (VOCs), and fatty acids). Samples from
      those SCB systems were collected three times a day for five non-consecutive days.
      According to our study, H(2)S recorded consistently the highest mean values of
      2554 ppb (wet) and 699 ppb (dry system) among all major offensive odorants. In
      contrast, the most prevalent VOCs were distinguished between methyl ethyl ketone
      (250 ppb in dry SCB) and toluene (32.8 ppb in wet SCB). In general, most odorants
      tend to exhibit relative enhancement in the afternoon, regardless of SCB types.
      If the concentration values of each odorant are converted into odor intensity
      (OI), the RSC group was identified as the key components of odor formation in
      SCB. If the OI values of each individual component are bound to yield sum of odor
      intensity (SOI), their values for wet and dry system were 4.99 and 4.25,
      respectively. In light of the fact that SCBs can serve as a potential odor source
      in urban areas, it should be managed and maintained properly to suppress the
      propagation of odor into the surrounding environments.

PMID- 20692682
TI  - Biodegradation pathway of mesotrione: complementarities of NMR, LC-NMR and LC-MS
      for qualitative and quantitative metabolic profiling.
AB  - Enhanced knowledge of pesticide transformation products formed in the environment
      could lead to both accurate estimates of the overall effects of these compounds
      on environmental ecosystems and human health and improved removal processes.
      These compounds can present chemical and environmental behaviours completely
      different from the starting active ingredient. The difficulty lies on their
      identification or/and their quantification due to the lack of analytical
      reference standards. In this context, ex situ Nuclear Magnetic Resonance (NMR)
      and Liquid Chromatography-NMR (LC-NMR) were used as complementary tools to LC
      Mass Spectrometry (MS) to define the metabolic pathway of mesotrione, an emergent
      herbicide, by the bacterial strain Bacillus sp. 3B6. The complementarities of ex
      situ and LC-NMR allowed us to unambiguously identify six metabolites whereas the
      structures of only four metabolites were suggested by LC-MS. The presence of a
      new metabolic pathway was evidenced by NMR. These results demonstrate that NMR
      and LC-NMR spectroscopy provided unambiguous structural information for
      xenobiotic metabolic profiling, even at moderate magnetic field and allowed
      direct absolute quantification despite the lack of commercial or synthetic
      standards, required for LC-MS techniques.

PMID- 20692683
TI  - Who were the makers of the Chatelperronian culture?

PMID- 20692684
TI  - Quantification of pathogenic microorganisms and microbial indicators in three
      wastewater reclamation and managed aquifer recharge facilities in Europe.
AB  - Managed Aquifer Recharge (MAR) is becoming an attractive option for water storage
      in water reuse processes as it provides an additional treatment barrier to
      improve recharged water quality and buffers seasonal variations of water supply
      and demand. To achieve a better understanding about the level of pathogenic
      microorganisms and their relation with microbial indicators in these systems,
      five waterborne pathogens and four microbial indicators were monitored over one
      year in three European MAR sites operated with reclaimed wastewater. Giardia and
      Cryptosporidium (oo)cysts were found in 63.2 and 36.7% of the samples
      respectively. Salmonella spp. and helminth eggs were more rarely detected (16.3%
      and 12.5% of the samples respectively) and Campylobacter cells were only found in
      2% of samples. At the Belgian site advanced tertiary treatment technology prior
      to soil aquifer treatment (SAT) produced effluent of drinking water quality, with
      no presence of the analysed pathogens. At the Spanish and Italian sites
      amelioration of microbiological water quality was observed between the MAR
      injectant and the recovered water. In particular Giardia levels decreased from
      0.24-6.14 cysts/L to 0-0.01 cysts/L and from 0.4-6.2 cysts/L to 0-0.07 cysts/L in
      the Spanish and Italian sites respectively. Salmonella gene copies and Giardia
      cysts were however found in the water for final use and/or the recovered
      groundwater water at the two sites. Significant positive Spearman correlations
      (p<0.05, r(s) range: 0.45-0.95) were obtained, in all the three sites, between
      Giardia cysts and the most resistant microbial markers, Clostridium spores and
      bacteriophages.

PMID- 20692685
TI  - Lead exposure is associated with a delay in the onset of puberty in South African
      adolescent females: findings from the Birth to Twenty cohort.
AB  - INTRODUCTION: One of the suggested, yet under-researched, causes of pubertal
      delay is lead exposure. In South Africa blood lead levels are generally higher
      than in resource-rich countries. Thus the effects of lead exposure on pubertal
      development may be significant. OBJECTIVE: The objective of this study is to
      determine the association between lead exposure and pubertal development in
      adolescent females in the Birth to Twenty cohort (Bt20). METHODS: Bt20 is a
      Johannesburg based birth cohort study that commenced in 1990 and includes 1682
      girls. At 13 years of age venous blood samples were collected from 725 adolescent
      female participants for lead content analyses; of these, 712 had menarche data.
      Pubertal measurement was based on age of menarche and self-reported Tanner
      staging for pubic hair (n=684) and breast development (n=682). RESULTS: The mean
      blood lead level for the sample was 4.9 microg/dl. Fifty percent had blood lead
      levels <5.0 microg/dl, 49% were > or = 5.0 microg/dl and 1% was >10.0 microg/dl.
      The average age of menarche was 12.7 years. At 13 years, 4% and 7% had reached
      Tanner stage 5 for pubic hair and breast development, respectively. Analyses
      showed that higher blood lead levels were associated with significant delays in
      the onset of puberty (p<0.001). CONCLUSION: The study found that higher blood
      lead levels were associated with a delay in the onset of puberty, after
      adjustment for confounders. Lead exposure in resource-poor countries is generally
      higher compared to resource-rich countries and thus the effects of high blood
      levels have personal and public health significance.

PMID- 20692686
TI  - Anthropogenic 129I in the atmosphere: overview over major sources, transport
      processes and deposition pattern.
AB  - Wet and, to a lesser extent, dry deposition of atmospheric (129)I are known to
      represent the dominating processes responsible for (129)I in continental
      environmental samples that are remote from (129)I sources and not directly
      influenced by any liquid (129)I release of nuclear installations. Up to now,
      however, little is known about the major emitters and the related global
      deposition pattern of (129)I. In this work an overview over major sources of
      (129)I is given, and hitherto unknown time-dependent releases from these were
      estimated. Total gaseous (129)I releases from the US and former Soviet
      reprocessing facilities Hanford, Savannah River, Mayak, Seversk and Zheleznogorsk
      were found to have been 0.53, 0.27, 1.05, 0.23 and 0.14TBq, respectively. These
      facilities were thus identified as major airborne (129)I emitters. The global
      deposition pattern due to the (129)I released, depending on geographic latitude
      and longitude, and on time was studied using a box model describing the global
      atmospheric transport and deposition of (129)I. The model predictions are
      compared to (129)I concentrations measured by means of Accelerator Mass
      Spectrometry (AMS) in water samples that were collected from various lakes in
      Asia, Africa, America and New Zealand, and to published values. As a result, both
      pattern and temporal evolution of (129)I deposition values measured in and
      calculated for different types of environmental samples are, in general, in good
      agreement. This supports our estimate on atmospheric (129)I releases and the
      considered substantial transport and deposition mechanisms in our model
      calculations.

PMID- 20692687
TI  - Greenhouse gases emissions and energy use of wheat grain-based bioethanol fuel
      blends.
AB  - This study focuses on the potential energetic and environmental impacts
      associated with the production of wheat grain-based bioethanol in Lombardia
      (Italy), with a "seed-to-wheel" approach (i.e. taking into account the production
      and use phase). Greenhouse gas emissions (GHGs) were estimated through the CML 2
      baseline 2000 methodology counting the CO(2) equivalent emissions, while the
      energy flow indicator was estimated using the Ecoindicator 95 methodology. The
      impact of the different phases involved in the production and use of bioethanol
      have been analysed: the agricultural production of wheat grain, its
      transformation into bioethanol, the production of gasoline and the use of 5
      different blends (from pure gasoline to pure ethanol). The results show that
      ethanol fuel, used in the form of blends in gasoline, can help reduce energy use
      and GHGs. In particular, the use of pure ethanol was found to be the best
      alternative presenting the lowest GHGs (saving about 32% of CO(2)eq emissions in
      comparison to gasoline) and the minor energy use (63% saving). Differences
      between low-ethanol blends and gasoline are minimal and dependent on the specific
      fuel consumption of the vehicle. The sensitivity analysis performed to test the
      robustness of results through the change of some basic assumptions (specific fuel
      consumption, N(2)O emissions from agricultural phase, allocation method) shows
      the sensitivity of GHGs saving to the adopted allocation method.

PMID- 20692688
TI  - Tumor grade at margins of resection in radical prostatectomy specimens is an
      independent predictor of prognosis.
AB  - OBJECTIVES: To assess whether reporting the grade of cancer at the site of
      positive margins in a radical prostatectomy (RP) specimen was independently
      prognostic of the outcome. METHODS: We restricted our study to 108 patients with
      Gleason score (GS) 7, nonfocal extraprostatic extension (EPE) (Stage pT3a), and
      positive surgical margins. Patients with a tertiary pattern 5, those who had
      received neoadjuvant therapy, and those with positive margins because of an
      intraprostatic incision were excluded. RESULTS: The overall GS was 3 + 4 in 73
      patients (67%) and 4 + 3 in 35 (33%). The median length of the positive margin
      was 3.0 mm (range 0.5-10). The GS at the margin was 3 + 3, 3 + 4, 4 + 3, and 4 +
      4 in 40 (37%), 41 (38%), 16 (14.8%), and 11 (10.2%) cases, respectively. Of the
      108 patients, 45 (42%) remained free of disease after RP (median follow-up 6
      years, range 3-13). Univariate and multivariate analyses showed no correlation
      between biochemical recurrence and either the preoperative serum prostate
      specific antigen level (P = .7) or overall GS (P = .5). A strong association was
      noted between biochemical recurrence and the GS at the positive surgical margin
      (P = .007), with length of cancer at the margin also predictive (P = .015) on
      multivariate analysis. Using the median length of the positive margin (3 mm) as
      the cutoff, the association with biochemical recurrence was significantly
      different between the 2 groups (P = .004) using Kaplan-Meier analysis.
      CONCLUSIONS: This is the first study to show that the grade of cancer at the site
      of a positive margin influences the outcome. We were able to stratify the grade
      into 3 categories: 3 + 3, 3 + 4, and 4 + 3 or greater (4 + 3 and 4 + 4 at the
      positive margin provided equal prognostic information).

PMID- 20692689
TI  - The diagnosis and management of anaphylaxis practice parameter: 2010 update.
AB  - These parameters were developed by the Joint Task Force on Practice Parameters,
      representing the American Academy of Allergy, Asthma & Immunology (AAAAI); the
      American College of Allergy, Asthma & Immunology (ACAAI); and the Joint Council
      of Allergy, Asthma and Immunology. The AAAAI and the ACAAI have jointly accepted
      responsibility for establishing "The Diagnosis and Management of Anaphylaxis
      Practice Parameter: 2010 Update." This is a complete and comprehensive document
      at the current time. The medical environment is a changing environment, and not
      all recommendations will be appropriate for all patients. Because this document
      incorporated the efforts of many participants, no single individual, including
      those who served on the Joint Task Force, is authorized to provide an official
      AAAAI or ACAAI interpretation of these practice parameters. Any request for
      information about or an interpretation of these practice parameters by the AAAAI
      or ACAAI should be directed to the Executive Offices of the AAAAI, the ACAAI, or
      the Joint Council of Allergy, Asthma and Immunology. These parameters are not
      designed for use by pharmaceutical companies in drug promotion.

PMID- 20692690
TI  - The US Food and Drug Administration and long-acting beta2-agonists: the
      importance of striking the right balance between risks and benefits of therapy?

PMID- 20692691
TI  - Translucency, opalescence and light transmission characteristics of light-cured
      resin composites.
AB  - OBJECTIVES: To evaluate the translucency, opalescence and light transmission
      characteristics of resin composites with different thicknesses. METHODS: Disks of
      three resin composites (Estelite?, Beautifil II, Clearfil Majesty) of A2 shade
      were prepared in diameter of 10mm with various thicknesses (0.5mm, 1.0mm and
      2.0mm). Color was measured according to CIELAB color scale on a reflection
      spectrophotometer and a color haze meter, and translucency parameter (TP) and
      opalescence parameter (OP) were calculated. Using the distribution graphs of
      transmitted light intensity on a goniophotometer, diffusion factor (DF) as an
      indicator for a diffuse transmission property and peak gain (G0) for a straight
      line transmission property were calculated. RESULTS: The TP and G0 values
      significantly decreased in the order: 0.5mm>1.0mm>2.0mm thickness (p<0.05). The
      OP value increased as the thickness of resin composite increased from 1.0mm to
      2.0mm (p<0.05), while was similar for the 0.5mm- and 1.0mm-thick groups. The DF
      value increased from 0.5mm to 1.0mm, but was similar for the 1.0mm- and 2.0mm
      thick groups. There was a significant correlation between TP and DF (R(2)=0.96,
      p<0.001). On the other hand, there was a weak correlation between OP and DF
      (R(2)=0.21, p<0.005), however within the values of the 0.5mm-thick group, OP was
      highly correlated with DF (R(2)=0.84, p<0.001). SIGNIFICANCE: At the 0.5mm
      thickness, the translucency (TP) and opalescence (OP) of resin composites had a
      significant correlation with a diffuse transmission property (DF). When more than
      1.0mm thickness of resin composites, translucency and opalescence were influenced
      by the thickness, in which translucency significantly decreased and opalescence
      significantly increased.

PMID- 20692692
TI  - STAT-C: a full revolution or just a step forward?

PMID- 20692694
TI  - Long-term monitoring using resident and caged mussels in Boston Harbor yield
      similar spatial and temporal trends in chemical contamination.
AB  - Measurements of chemical contaminants in caged (transplanted) and resident mussel
      populations have become a routine tool for monitoring and assessing the status
      and trends of coastal water quality. However, few long-term data sets are
      available to assess the comparability and efficacy of these two monitoring
      approaches. Three long-term independent data sets exist for Boston Harbor: the
      National Mussel Watch program has analyzed resident blue mussels (Mytilus edulis)
      from the Boston Harbor/Massachusetts Bay region for over twenty years, the
      Massachusetts Water Resources Authority has annually deployed caged
      (transplanted) mussels (M. edulis) to assess bioaccumulation potential of sewage
      effluent discharged under its NPDES permit for over fourteen years, and the
      GulfWatch program has analyzed resident blue mussel populations for over twelve
      years. Together, these data provide consistent and comparable information on
      temporal and spatial changes in chemical contamination in Boston Harbor as steps
      were taken to reduce contaminant loading. The data also demonstrate the
      complementary nature of resident and caged (transplanted) mussels for assessing
      contaminant trends even when the basic approaches and sampling frequency differ.
      These fifteen-year data sets demonstrate contaminant concentrations in mussels
      from Boston Harbor are similar and with few exceptions have significantly
      decreased since the early 1990s. The observed trends also demonstrate broad scale
      improvements to the quality of Boston Harbor and expand understanding of the
      response of coastal systems to interventions that reduce the load of chemicals to
      the ocean.

PMID- 20692693
TI  - Efficacy of boceprevir, an NS3 protease inhibitor, in combination with
      peginterferon alfa-2b and ribavirin in treatment-naive patients with genotype 1
      hepatitis C infection (SPRINT-1): an open-label, randomised, multicentre phase 2
      trial.
AB  - BACKGROUND: Peginterferon plus ribavirin achieves sustained virological response
      (SVR) in fewer than half of patients with genotype 1 chronic hepatitis C virus
      infection treated for 48 weeks. We tested the efficacy of boceprevir, an NS3
      hepatitis C virus oral protease inhibitor, when added to peginterferon alfa-2b
      and ribavirin. METHODS: In part 1 of this trial, undertaken in 67 sites in the
      USA, Canada, and Europe, 520 treatment-naive patients with genotype 1 hepatitis C
      virus infection were randomly assigned to receive peginterferon alfa-2b 1.5
      mug/kg plus ribavirin 800-1400 mg daily for 48 weeks (PR48; n=104); peginterferon
      alfa-2b and ribavirin daily for 4 weeks, followed by peginterferon alfa-2b,
      ribavirin, and boceprevir 800 mg three times a day for 24 weeks (PR4/PRB24;
      n=103) or 44 weeks (PR4/PRB44; n=103); or peginterferon alfa-2b, ribavirin, and
      boceprevir three times a day for 28 weeks (PRB28; n=107) or 48 weeks (PRB48;
      n=103). In part 2, 75 patients were randomly assigned to receive either PRB48
      (n=16) or low-dose ribavirin (400-1000 mg) plus peginterferon alfa-2b and
      boceprevir three times a day for 48 weeks (low-dose PRB48; n=59). Randomisation
      was by computer-generated code, and study personnel and patients were not masked
      to group assignment. The primary endpoint was SVR 24 weeks after treatment.
      Analysis was by intention to treat. This study is registered with
      ClinicalTrials.gov, number NCT00423670. FINDINGS: Patients in all four boceprevir
      groups had higher rates of SVR than did the control group (58/107 [54%, 95% CI 44
      64], p=0.013 for PRB28; 58/103 [56%, 44-66], p=0.005 for PR4/PRB24; 69/103 [67%,
      57-76], p<0.0001 for PRB48; and 77/103 [75%, 65-83], p<0.0001 for PR4/PRB44; vs
      39/104 [38%, 28-48] for PR48 control). Low-dose ribavirin was associated with a
      high rate of viral breakthrough (16/59 [27%]), and a rate of relapse (six of 27
      [22%]) similar to control (12/51 [24%]). Boceprevir-based groups had higher rates
      of anaemia (227/416 [55%] vs 35/104 [34%]) and dysgeusia (111/416 [27%] vs nine
      of 104 [9%]) than did the control group. INTERPRETATION: In patients with
      untreated genotype 1 chronic hepatitis C infection, the addition of the direct
      acting antiviral agent boceprevir to standard treatment with peginterferon and
      ribavirin after a 4-week lead-in seems to have the potential to double the
      sustained response rate compared with that recorded with standard treatment
      alone. FUNDING: Merck.

PMID- 20692695
TI  - Injectable, dual cross-linkable polyphosphazene blend hydrogels.
AB  - A new class of injectable, self cross-linkable, and thermosensitive
      polyphosphazene-based blending systems of functional thiolated and acrylated
      polymers was designed and synthesized to develop an ideal injectable carrier, and
      to overcome many barriers associated with developing the injectable carriers,
      such as the uses of monomeric crosslinkers, catalysts, oxidants, pH adjustments,
      initiators, UV light, heat production and organic solvent. The aqueous solutions
      of the polymer blends were exhibited a solution state at low temperature, and
      transformed into a hydrogel state with desired mechanical strength at body
      temperature via thermosensitive hydrophobic interactions. The mechanical strength
      was further improved by the cross-linking of thiol groups with acrylate groups in
      the polymer network under physiological conditions. The thermoresponsive
      hydrophobic interactions in the polymer network accelerated the chemical cross
      linking to improve the mechanical property. The mechanical strength, inner three
      dimensional network, and degradation rate can be tuned through the degree of
      cross-linking between the thermosensitive and functional blended polymers. The
      results suggest that the self cross-linkable thermosensitive polyphosphazene
      blend systems have great potentials to play a crucial role as an injectable
      carrier because of their improved suitable mechanical properties for application
      potentials, in addition to their inherent advantages such as injectable,
      biodegradable and thermosensitive properties.

PMID- 20692696
TI  - Nanodiamonds as intracellular transporters of chemotherapeutic drug.
AB  - To explore the application of nanodiamonds (NDs) as anticancer drug delivery
      vehicles, firstly we examined the toxicity of NDs to three kinds of mammalian
      cells. The studies indicated that serum proteins in cell culture medium had
      significant effect. When cells were exposed to NDs dispersed in complete cell
      culture medium, no cytotoxicity was detected. However, severe cell death was
      found after exposed to NDs dispersed in serum-free medium. Possible reasons for
      serum-dependent cytotoxicity were discussed and the potential influence of serum
      on the test of efficacy was pointed for anticancer drug delivery system based on
      NDs. Then adsorption of anticancer drug 10-hydroxycamptothecin (HCPT) by NDs was
      studied. Experiments indicated that diluted NaOH solution could promote the
      loading of HCPT on NDs. And a slow release of HCPT from the HCPT-ND complex was
      established in low pH media. Assessments of cell viability and imaging with
      transmission electron microscopy demonstrated a much higher efficacy of the HCPT
      ND complex compared with HCPT alone. On the basis of adsorption feature of ND
      aggregates, new strategy for the design of targeting drug delivery systems of NDs
      was proposed.

PMID- 20692697
TI  - Neurotoxicological effects and the impairment of spatial recognition memory in
      mice caused by exposure to TiO2 nanoparticles.
AB  - Titanium dioxide nanoparticles (TiO(2) NPs) are now in daily use including
      popular sunscreens, toothpastes, and cosmetics. However, the effects of TiO(2)
      NPs on human body, especially on the central nervous system, are still unclear.
      The aim of this study was to determine whether TiO(2) NPs exposure results in
      persistent alternations in nervous system function. ICR mice were exposed to
      TiO(2) NPs through intragastric administration at 0, 5, 10 and 50 mg/kg body
      weight every day for 60 days. The Y-maze test showed that TiO(2) NPs exposure
      could significantly impair the behaviors of spatial recognition memory. To fully
      investigate the neurotoxicological consequence of TiO(2) NPs exposure, brain
      elements and neurochemicals were also investigated. The contents of Ca, Mg, Na,
      K, Fe and Zn in brain were significantly altered after TiO(2) NPs exposure.
      Moreover, TiO(2) NPs significantly inhibited the activities of Na(+)/K(+)-ATPase,
      Ca(2+)-ATPase, Ca(2+)/Mg(2+)-ATPase, acetylcholine esterase, and nitric oxide
      synthase; the function of the central cholinergic system was also noticeably
      disturbed and the contents of some monoamines neurotransmitters such as
      norepinephrine, dopamine and its metabolite 3, 4-dihydroxyphenylacetic acid, 5
      hydroxytryptamine and its metabolite 5-hydroxyindoleacetic acid were
      significantly decreased, while the contents of acetylcholine, glutamate, and
      nitric oxide were significantly increased. These first findings indicated that
      exposure to TiO(2) NPs could possibly impair the spatial recognition memory
      ability, and this deficit may be possibly attributed to the disturbance of the
      homeostasis of trace elements, enzymes and neurotransmitter systems in the mouse
      brain. Therefore, the application of TiO(2) NPs and exposure effects especially
      on human brain for long-term and low-dose treatment should be cautious.

PMID- 20692698
TI  - A polymer microstructure array for the formation, culturing, and high throughput
      drug screening of breast cancer spheroids.
AB  - Multicellular spheroid models have been recognized as superior to monolayer cell
      cultures in antitumor drug screening, but their commercial adaptation in the
      pharmaceutical industry has been delayed, primarily due to technological
      limitations. The current study presents a new spheroid culture platform that
      addresses these technical restrictions. The new culturing device is based on a
      multiwell plate equipped with a glass bottom patterned with an array of UV
      adhesive microchambers. Each microchamber is designed to accommodate a single
      spheroid. The system facilitates the simultaneous creation and culturing of a
      large number of spheroids, as well as screening their response to antitumor
      drugs. The volume of the spheroids is easily controlled by seeding density. The
      location of each spheroid is preserved in the same microchamber throughout its
      growth, treatment with soluble agents, and imaging. The growth ratio parameter, a
      non-intrusive size analysis of the same spheroid before and after exposure to
      drugs, was found to be a sensitive indicator for the reaction of MCF7 breast
      cancer spheroids to cytotoxic drugs. This feature helps reveal the heterogeneity
      within the spheroid population during the formation process and their drug
      response, and provides an opportunity to detect specific, highly active or drug
      resistant spheroid sub-groups. The advantages of this spheroid-based system make
      it an efficient drug-screening tool that may be valuable to related fields of
      research and clinical applications.

PMID- 20692699
TI  - Mechanical and biological characteristics of diamond-like carbon coated poly aryl
      ether-ether-ketone.
AB  - Poly aryl-ether-ether-ketone (PEEK) is an alternative to metal alloys in
      orthopedic applications. Although the polymer provides many significant
      advantages such as excellent mechanical properties and non-toxicity, it suffers
      from insufficient elasticity and biocompatibility. Since the elastic modulus of
      diamond-like carbon (DLC) is closer to that of cortical bone than PEEK, the
      DLC/PEEK combination is expected to enhance the stability and surface properties
      of PEEK in bone replacements. In this work, PEEK is coated with diamond-like
      carbon (DLC) by plasma immersion ion implantation and deposition (PIII&D) to
      enhance the surface properties. X-ray photoelectron spectrometry (XPS), Raman
      spectroscopy, and Fourier transform infrared (FTIR) spectroscopy demonstrate
      successful deposition of the DLC film on PEEK without an obvious interface due to
      energetic ion bombardment. Atomic force microscopy (AFM) and contact angle
      measurements indicate changes in the surface roughness and hydrophilicity, and
      nanoindentation measurements reveal improved surface hardness on the DLC/PEEK.
      Cell viability assay, scanning electron microscopy (SEM), and real-time PCR
      analysis show that osteoblast attachment, proliferation, and differentiation are
      better on DLC/PEEK than PEEK. DLC/PEEK produced by PIII&D combines the advantages
      of DLC and PEEK and is more suitable for bone or cartilage replacements.

PMID- 20692700
TI  - Debye function analysis and 2D imaging of nanoscaled engineered bone.
AB  - The Debye Function Analysis of diffraction patterns from nanosized mineral
      crystals showing different average degrees of maturity was carried out on
      engineered bone samples. The analysis relied on a bivariate family of atomistic
      hydroxyapatite nanocrystal models and provided information about crystal
      structure, size and shape distributions of the mineral component of the newly
      formed bone. An average rod-like shape of nanocrystals was found in all samples,
      with average sizes well matching the collagen I gap region. The diffraction
      patterns investigated through the Debye Function Analysis were used as signal
      models to perform the Canonical Correlation Analysis of high resolution X-ray
      micro-diffraction patterns collected on porous and resorbable
      hydroxyapatite/silicon-stabilized tricalcium phosphate (Si-TCP) implants. The
      nosologic maps clearly showed a size gradient in the new formed bone that
      validates the mechanism (mimicking the bone remodelling in orthotopic bones) of a
      continuous deposition of bone by osteoblasts, an increasing mineralization of the
      newly deposited bone, a growth of the new crystals, at the same time that
      osteoclasts adhere to the scaffold surface and resorb the bioceramic. The
      comparison of samples at different implantation times proved that the selective
      resorption of Si-TCP component from the scaffold was already evident after two
      and almost complete after six months.

PMID- 20692701
TI  - Polyion complex stability and gene silencing efficiency with a siRNA-grafted
      polymer delivery system.
AB  - An siRNA-grafted polymer through disulfide linkage was prepared to improve the
      physicochemical properties and transfection efficacies of the polyion complexes
      (PICs) as a nanocarrier of siRNA. The siRNA-grafted polymer formed stable PICs
      due to its larger numbers and higher density of anionic charges compared with
      monomeric siRNA, leading to effective internalization by cultured cells.
      Following the endosomal escape of the PIC, the disulfide linkage of the siRNA
      grafted polymer allowed efficient siRNA release from the PIC under intracellular
      reductive conditions. Consequently, the PIC from the siRNA-grafted polymer showed
      a potent gene silencing effect without cytotoxicity or immunogenicity,
      demonstrating a promising feature of the siRNA-grafted polymer to construct the
      PIC-based nanocarrier for in vivo siRNA delivery.

PMID- 20692702
TI  - Functionalised polysiloxanes as injectable, in situ curable accommodating
      intraocular lenses.
AB  - The aged eye's ability to change focus (accommodation) may be restored by
      replacing the hardened natural lens with a soft gel. Functionalised polysiloxane
      macromonomers, designed for application as an injectable, in situ curable
      accommodating intraocular lens (A-IOL), were prepared via a two-step synthesis.
      Prepolymers were synthesised via ring opening polymerisation (ROP) of
      octamethylcyclotetrasiloxane (D(4)) and 2,4,6,8-tetramethylcyclotetrasiloxane
      (D(4)(H)) in toluene using trifluoromethanesulfonic acid (TfOH) as catalyst.
      Hexaethyldisiloxane (HEDS) was used as the end group to control the molecular
      weight of the prepolymers, which were then converted to macromonomers by
      hydrosilylation of the SiH groups with allyl methacrylate (AM) to introduce
      polymerisable groups. The resulting macromonomers had an injectable consistency
      and thus, were able to be injected into and refill the empty lens capsular bag.
      The macromonomers also contained a low ratio of polymerisable groups so that they
      may be cured on demand, in situ, under irradiation of blue light, in the presence
      of a photo-initiator, to form a soft polysiloxane gel (an intraocular lens) in
      the eye. The pre-cure viscosity and post-cure modulus of the polysiloxanes, which
      are crucial factors for an injectable, in situ curable A-IOL application, were
      controlled by adjusting the end group and D(4)(H) concentrations, respectively,
      in the ROP. The macromonomers were fully cured within 5 min under light
      irradiation, as shown by the rapid change in modulus monitored by photo-rheology.
      Ex vivo primate lens stretching experiments on an Ex Vivo Accommodation Simulator
      (EVAS) showed that the polysiloxane gel refilled lenses achieved over 60% of the
      accommodation amplitude of the natural lens. An in vivo biocompatibility study in
      rabbits using the lens refilling (Phaco-Ersatz) procedure demonstrated that the
      soft gels had good biocompatibility with the ocular tissue. The polysiloxane
      macromonomers meet the targeted optical and mechanical properties of a young
      natural crystalline lens and show promise as candidate materials for use as
      injectable, in situ curable A-IOLs for lens refilling procedures.

PMID- 20692703
TI  - The generation of 3-D tissue models based on hyaluronan hydrogel-coated
      microcarriers within a rotating wall vessel bioreactor.
AB  - With the increasing necessity for functional tissue- and organ equivalents in the
      clinic, the optimization of techniques for the in vitro generation of organotypic
      structures that closely resemble the native tissue is of paramount importance.
      The engineering of a variety of highly differentiated tissues has been achieved
      using the rotating wall vessel (RWV) bioreactor technology, which is an optimized
      suspension culture allowing cells to grow in three-dimensions (3-D). However,
      certain cell types require the use of scaffolds, such as collagen-coated
      microcarrier beads, for optimal growth and differentiation in the RWV. Removal of
      the 3-D structures from the microcarriers involves enzymatic treatment, which
      disrupts the delicate 3-D architecture and makes it inapplicable for potential
      implantation. Therefore, we designed a microcarrier bead coated with a synthetic
      extracellular matrix (ECM) composed of a disulfide-crosslinked hyaluronan and
      gelatin hydrogel for 3-D tissue engineering, that allows for enzyme-free cell
      detachment under mild reductive conditions (i.e. by a thiol-disulfide exchange
      reaction). The ECM-coated beads (ECB) served as scaffold to culture human
      intestinal epithelial cells (Int-407) in the RWV, which formed viable multi
      layered cell aggregates and expressed epithelial differentiation markers. The
      cell aggregates remained viable following dissociation from the microcarriers,
      and could be returned to the RWV bioreactor for further culturing into bead-free
      tissue assemblies. The developed ECBs thus offer the potential to generate
      scaffold-free 3-D tissue assemblies, which could further be explored for tissue
      replacement and remodeling.

PMID- 20692704
TI  - Can we colonize the solar system? Human biology and survival in the extreme space
      environment.
AB  - Throughout the history of the space age the dominant vision for the future has
      been great spaceships plying the solar system, and perhaps beyond, moving living
      beings from one planet to another. Spacesuited astronauts would carry out
      exploration, colonization, and settlement as part of a relentlessly forward
      looking movement of humanity beyond Earth. As time has progressed this image has
      not changed appreciably even as the full magnitude of the challenges it
      represents have become more and more apparent. This essay explores the issues
      associated with the human movement beyond Earth and raises questions about
      whether humanity will ever be able to survive in the extreme environment of space
      and the other bodies of the solar system. This paper deals with important
      historical episodes as well as wider conceptual issues about life in space. Two
      models of expansion beyond Earth are discussed: (1) the movement of microbes and
      other types of life on Earth that can survive the space environment and (2) the
      modification of humans into cyborgs for greater capability to survive in the
      extreme environments encountered beyond this planet.

PMID- 20692705
TI  - An integrated model of risk and protective factors for post-deployment PTSD
      symptoms in OEF/OIF era combat veterans.
AB  - BACKGROUND: Few attempts have been made to integrate the known risk factors for
      combat-related posttraumatic stress disorder (PTSD) into a comprehensive model.
      This study investigated relative contributions of combat experiences, post-battle
      experiences, and perceptions of threat to post-deployment PTSD symptoms, and also
      examined whether pre-deployment preparedness moderated associations among these
      variables. METHODS: Two hundred seven troops deployed to the Middle East between
      2001 and 2008 completed self-report measures. Data were analyzed using path
      analysis and regressions. A comprehensive model including additive effects,
      mediation, and moderation was examined. RESULTS: Perceptions of threat mediated
      the association of combat experiences with PTSD, but not that of post-battle
      experiences with PTSD. Sense of preparedness for deployment moderated the
      association of combat experiences with perceived threat, such that troops with
      low preparedness perceived high levels of threat regardless of combat exposure,
      whereas troops with high preparedness perceived levels of threat that were
      correlated with levels of combat. LIMITATIONS: Data were cross-sectional, all
      assessment was retrospective self-report, and the sample was primarily White,
      male, and married. CONCLUSIONS: Combat and post-battle experiences appear linked
      to PTSD via separate pathways. Thus, PTSD prevention efforts may need to vary
      based on types of events experienced. Pre-deployment preparation mitigated
      perceived threat in the context of low combat exposure, but it did not moderate
      direct associations of risk factors with PTSD symptoms. Thus, pre-deployment
      training and preparation do not appear sufficient to protect against PTSD.

PMID- 20692706
TI  - Range and specificity of war-related trauma to posttraumatic stress; depression
      and general health perception: displaced former World War II children in late
      life.
AB  - BACKGROUND: Dose-response relation of war experiences and posttraumatic stress,
      depression and poor health functioning in late life is well documented in war
      affected populations. The influence of differing trauma types experienced by war
      affected population in the study of dose-response relation of war trauma and
      psychological maladaptation in late life has not been investigated. We examined a
      subgroup of displaced elders and investigated whether specific trauma types were
      associated with differential health outcomes. METHODS: From representative
      practitioner lists, matched groups of former displaced and non-displaced World
      War II children were assigned, yielding a total sample of 417 participants
      (response rate 50%). Measurement encompassed a self-report survey including the
      Impact of Event Scale-Revised, the Patient Health Questionnaire and the Harvard
      Trauma Questionnaire. RESULTS: Consistent dose-relation between war-related
      experiences and posttraumatic stress or depressive symptoms in late life was
      found for both, displaced and non-displaced elders, whereas a gradient for poor
      health perception was only found in displaced people. Trauma types derived from
      principal component analysis showed differential associations with health
      outcomes. Human Right Violations emerged as risk factor for posttraumatic stress
      symptoms and Deprivation & Threat to Life as risk factor for depressive symptoms.
      Poor self-rated health was associated with multiple trauma types. LIMITATIONS:
      Non-random recruitment, retrospective design and use of self-report. CONCLUSIONS:
      Posttraumatic stress and depression are associated with war-related experiences
      more than 60 years after World War II. Results suggest that different trauma
      types lead to unique variants of syndrome configurations, which may result from
      different etiological factors.

PMID- 20692707
TI  - Painting "mania".
AB  - Bipolar mood disorder (manic-depressive illness) has many artistic references,
      especially in the painting domain, depicting moods and associated features. The
      title of some paintings directly refers to the psychopathological state of the
      disorder. There are a great number of painting masterpieces showing the
      depressive pole of manic-depressive illness. In some paintings bearing the title
      Melancholia, some admixture of the opposite manic pole can be traced, the
      phenomenon named today as "mixed depressive state". On the other hand, a painting
      depicting a pure manic pole, as an element of bipolar mood disorder is very
      difficult to find. However, it seems that such criteria could be met by the
      painting presented on the next page entitled "Mania" whose author is Florencio
      Yllana, a contemporary artist of Philippine origin (born 1977), studying in USA
      and presently living in Brazil. The painting was done in 2001 following the acute
      manic episode in the course of bipolar mood disorder in the artist.

PMID- 20692708
TI  - Dimensional measures of personality as a predictor of outcome at 5-year follow-up
      in women with bulimia nervosa.
AB  - Dimensional models are commonly used as a supplement to the categorical model
      within the field of personality disorders. The purpose of this study was to
      examine personality dimensions as predictors of 5-year outcomes among women with
      bulimia nervosa. One hundred and thirty-four women with bulimia nervosa
      participated in a randomised psychotherapy treatment trial. Data was available
      for 109 out of the 134 participants at follow-up. Outcomes were the presence of
      any eating disorder (past year), the presence of a mood disorder episode (past
      year), and the global assessment of functioning at 5-year follow-up. Self
      directedness was the only predictor of any eating disorder diagnosis (past year)
      at 5-year follow-up. Asceticism significantly predicted the presence of a mood
      disorder episode (past year) at 5 years. Borderline personality disorder symptoms
      predicted global functioning at 5 years. These results suggest that high self
      directedness at pre-treatment may offer potential prognostic information
      regarding eating disorder status 5 years post-treatment. Furthermore, no single
      measure predicted outcome for all variables (any eating disorder diagnosis, a
      mood disorder episode (past year), or global functioning) at 5-year follow-up.
      This suggests that a comprehensive personality assessment using multiple measures
      is desirable for predicting outcomes.

PMID- 20692709
TI  - Assessment of standard coil positioning in transcranial magnetic stimulation in
      depression.
AB  - Transcranial magnetic stimulation (TMS) is a non-invasive technique used in the
      treatment of major depression. Meta-analyses have shown that it is more efficient
      than a placebo and that its efficacy is enhanced by the optimum tuning of
      stimulation parameters. However, the stimulation target, the dorsolateral
      prefrontal cortex (DLPFC), is still located using an inaccurate method. In this
      study, a neuronavigation system was used to perform a comprehensive
      quantification of target localization errors. We identified and quantified 3
      sources of error in the standard method: cap repositioning, interexpert
      variability in coil positioning and distance between the stimulated point and the
      expected target. For cap repositioning, the standard deviation was lower than 5mm
      in the 3 axes. For interexpert variability in coil positioning, the spatial
      dispersion of the points was higher than 10mm in 2 of the 3 axes. For
      interindividual anatomical variability, the distance between the actual
      "reference" DLPFC and its standard determination was greater than 20mm for 54% of
      the subjects, while one subject out of eleven was correctly targeted which means
      10mm or less from the reference. Results showed that interindividual anatomical
      variability and interexpert variability were the two main sources of error using
      the standard method. Results demonstrate that a neuronavigation system is
      mandatory to conduct reproducible and reliable studies.

PMID- 20692710
TI  - Characterization of monoclonal antibodies against goat interleukin-18 and their
      application in the measurement of goat interleukin-18 in LPS-stimulated
      peripheral blood mononuclear cells by sandwich ELISA.
AB  - In order to develop a specific assay for the measurement of goat IL-18 level, two
      stable hybridoma cell lines were established which secreted IgG1 monoclonal
      antibodies (mAbs) against goat IL-18. Specific binding of two mAbs named 2E8 and
      4C4 to recombinant goat IL-18 expressed in Escherichia coli was demonstrated in
      an ELISA and Western blotting. Results also showed that mAbs 2E8 and 4C4 bound to
      distinct epitopes in the ELISA additivity test. These two mAbs were applied in
      IFA analysis for the detection of goat IL-18 expressed in 293FT cells and in the
      sandwich ELISA for the measurement of goat IL-18 levels in LPS-stimulated PBMC.
      Results from this study demonstrated that mAbs against goat IL-18 recognize
      bovine and human IL-18 and could be used to measure IL-18 levels in different
      inflammations or immune responses in future studies.

PMID- 20692711
TI  - Not a "sound" decision: is cochlear implantation always the best choice?
AB  - OBJECTIVE: To review the candidacy criteria used to counsel parents of profoundly
      deaf children, to determine if these criteria have changed over time, and to
      evaluate eventual communication outcomes for these patients. DESIGN:
      Retrospective review of 483 pediatric cochlear implant candidates from September
      1995 to December 2006 seen at a tertiary care pediatric hospital. RESULTS: Out of
      483 implant candidates, 191 patients were initially felt not to be favorable
      candidates based on CI team evaluation. Of this group, 3 had insufficient records
      to review and were excluded. The remaining 188 patients underwent a detailed
      analysis of specific possible contraindications to implantation. This included
      audiologic, medical and psychosocial parameters. The data was divided into two
      time periods: Group 1 included 44 patients from 1995 to 2000, and Group 2
      included 144 patients from 2001 to 2006. In Group 1, there was a higher
      percentage of children with language deprivation and developmental concerns and
      patients not ready, compared to Group 2 which had a higher percentage of families
      not ready and inadequate support systems. Group 1 had a higher percentage of
      patients who ultimately underwent cochlear implant, but otherwise the two groups
      were largely similar. CONCLUSION: Analysis of our data showed that the degree of
      concern that the cochlear implant team has in relationship to specific candidacy
      criteria has changed over time. Recommendations against a cochlear implant were
      often revisited after initial concerns were addressed. The use of a team
      approach, in conjunction with a validation tool, is important for establishing
      criteria for successful cochlear implantation in children to support appropriate
      counseling of patients and families and to plan post-implant management.

PMID- 20692712
TI  - Vascular remodeling in pulmonary arterial hypertension: multiple cancer-like
      pathways and possible treatment modalities.
AB  - Most patients with severe pulmonary arterial hypertension (PAH) demonstrate
      persistent structural alterations in small pulmonary arterioles at the time of
      diagnosis, including marked proliferation of pulmonary artery endothelial cells
      (ECs), smooth muscle cells (SMCs) and fibroblasts. Rai et al. have recently
      proposed a paradigm shift to explain the pathobiology of small vessel disease in
      severe PAH patients as a quasi-neoplastic process. Indeed, the vascular lesions
      of patients with severe PAH exhibit some cancer-like characteristics: decreased
      population of apoptotic cells and overexpression of antiapoptotic proteins.
      Nevertheless they lack the capability for tissue invasion and metastasis. The
      article reviews pathomechanisms of vascular lesions in PAH comparing them with
      each of the cancer defining mechanisms and indicates the potential utility of
      antineoplastic drugs as antiproliferative treatment in PAH. PDGF has been
      identified as a novel potential therapeutic target and the successful treatment
      of experimental PAH with a PDGF receptor tyrosine kinase inhibitor has been
      demonstrated recently. These findings justify further clinical trials concerning
      thyrosine kinase inhibitors as future PAH therapies. However, the drugs currently
      developed for malignant neoplasms to target neoplastic proliferation should be
      tested carefully in PAH patients due to their cardiac and pulmonary toxicity.

PMID- 20692713
TI  - Calcific cardiac disease: a comprehensive investigation into its true nature.

PMID- 20692715
TI  - A patient specific electro-mechanical model of the heart.
AB  - This paper presents a patient specific deformable heart model that involves the
      known electrical and mechanical properties of the cardiac cells and tissue. The
      whole heart model comprises ten Tusscher's ventricular and Nygren's atrial cell
      models, the anatomical and electrophysiological model descriptions of the atria
      (introduced by Harrild et al.) and ventricle (given by Winslow et al.), and the
      mechanical model of the periodical cardiac contraction and resting phenomena
      proposed by Moireau et al. During the propagation of the depolarization wave, the
      kinetic, compositional and rotational anisotropy is handled by the tissue, organ
      and torso model. The applied patient specific parameters were determined by an
      evolutionary computation method. An intensive parameter reduction was performed
      using the abstract formulation of the searching space. This patient specific
      parameter representation enables the adjustment of deformable model parameters in
      real-time. The validation process was performed using simultaneously measured ECG
      and ultrasound image records that were compared with simulated signals and shapes
      using an abstract, parameterized evaluation criterion.

PMID- 20692714
TI  - Psoriasis genetics: breaking the barrier.
AB  - Psoriasis is a common incurable inflammatory skin disease affecting 2-3% of the
      European population. Psoriatic skin contains large numbers of immune cells which
      produce many cytokines, chemokines and inflammatory molecules. The epidermis
      divides much faster than normal and has a defective outer layer or barrier which
      under normal circumstances protects from infection and dehydration. Psoriatic
      skin is characterized by a distinct set of inflammation and epidermal
      proliferation and differentiation markers, and it has been unclear whether the
      genetic basis of psoriasis reflects defects of the immune system or of the skin.
      One genetic determinant lies within the major histocompatibility complex class 1
      region. Genome-wide association studies have revealed genetic susceptibility
      factors that play a role in the formation of immune cells found in psoriasis
      lesions. Others affect epidermal proliferation and skin barrier formation. Hence,
      genetic components of both the immune system and the epidermis can predispose to
      disease.

PMID- 20692716
TI  - Dennexin peptides modeled after the homophilic binding sites of the neural cell
      adhesion molecule (NCAM) promote neuronal survival, modify cell adhesion and
      impair spatial learning.
AB  - Neural cell adhesion molecule (NCAM)-mediated cell adhesion results in activation
      of intracellular signaling cascades that lead to cellular responses such as
      neurite outgrowth, neuronal survival, and modulation of synaptic activity
      associated with cognitive processes. The crystal structure of the immunoglobulin
      (Ig) 1-2-3 fragment of the NCAM ectodomain has revealed novel mechanisms for NCAM
      homophilic adhesion. The present study addressed the biological significance of
      the so called dense zipper formation of NCAM. Two peptides, termed dennexinA and
      dennexinB, were modeled after the contact interfaces between Ig1 and Ig3 and
      between Ig2 and Ig2, respectively, observed in the crystal structure. Although
      the two dennexin peptides differed in amino acid sequence, they both modulated
      cell adhesion, reflected by inhibition of NCAM-mediated neurite outgrowth. Both
      dennexins also promoted neuronal survival, and the effect of dennexinA was
      independent of polysialic acid expression. Consistent with the effect of
      dennexinA on NCAM-mediated adhesion in vitro, the peptide impaired long-term
      memory retention in rats in the Morris water maze test. Thus, dennexins are novel
      site-specific pharmacological tools for elucidation of the role of NCAM in a
      variety of biological processes under normal and pathological conditions.

PMID- 20692717
TI  - Analysis by phage display selection and site-directed retromutagenesis of the
      Mustard Trypsin Inhibitor 2 reactive site.
AB  - The Mustard Trypsin Inhibitor (MSI) family is a small family of plant protease
      inhibitors so far only found in Brassicaceae. Using a phage display selection,
      MTI-2 (Mustard Trypsin Inhibitor 2) mutants were detected and analysed for their
      biochemical characteristics. Retromutants of the selected MTI-2 proteins were
      constructed and expressed in the Pichia pastoris system. The recombinant proteins
      were analysed by activity assays against bovine trypsin and Helicoverpa zea
      trypsin, and by circular dichroism. These analyses suggest a strict requirement
      for a specific proline residue adjacent to the inhibitor reactive site and give
      additional insights for future phage display application.

PMID- 20692718
TI  - [Retinal nerve fiber layer in OCT 3: prospective study of 53 normal children].
AB  - PURPOSE: To measure the peripapillary retinal nerve fiber layer thickness (RNFL
      thickness) in normal children using optical coherence tomography (OCT) and
      evaluate the effects of several factors on RNFL thickness, in order to complete
      results of other studies on this topic. MATERIAL AND METHOD: One hundred and four
      eyes of 53 normal children were investigated using OCT (Stratus OCT 3, Carl Zeiss
      Meditec, Dublin, CA, USA) measuring the RNFL thickness. These 28 boys and 25
      girls had a mean age of 9.68+/-3.02 years (range, 4-15 years) and a mean
      refraction in spherical equivalent of +1.79+/-2.11 diopters (range, -3.50-5.75).
      The effects of age, sex, and refraction on RNFL thickness were statistically
      analyzed with the SPSS Package (version 15, Chicago, IL, USA). RESULTS: RNFL
      thickness was 104.33+/-10.22 MUm (range, 85.87-145.82). RNFL thickness was
      greatest inferiorly (132.99+/-16.36 MUm) and superiorly (130.72+/-19.51 MUm),
      thinner nasally (79.01+/-18.48 MUm), and thinnest temporally (73.79+/-12.61 MUm).
      In univariate regression analysis, age had no significant effect on refraction
      and RNFL thickness. In univariate and multivariate analysis, refraction had a
      significant effect only on temporal (p<0.001) RNFL thickness. CONCLUSION: OCT can
      be used to measure RNFL thickness in children. This study confirms normal
      children's RNFL thickness data, which can be useful to the clinician in
      evaluating and treating optic nerve disorders in children.

PMID- 20692719
TI  - [Congenital retinal macrovessel associated with central serous retinopathy].
AB  - Retinal macrovessel is a rare disease. Since the first description in 1869 by
      Mauthner, fewer than 30 cases have been reported. We report a case of congenital
      retinal macrovessel in a 28-year-old patient with no pathological history. The
      patient consulted for functional macular syndrome (decreased visual acuity,
      central scotoma). In the right eye, the ophthalmologic examination found a visual
      acuity of ten over ten and serous detachment of the macular area. Examination of
      the left eye demonstrated the temporal vein crossing the macular area, without
      hemorrhage or exudates. Fluorescein angiography confirmed the diagnosis of
      bilateral central serous chorioretinitis with a congenital retinal macrovessel
      without leakage or arteriovenous anastomosis. Progression was marked by a
      disappearance of central serous retinopathy and visual recovery to ten over ten.
      In light of a literature review, we discuss the clinical classification of this
      disease and its developmental profile. The etiology of congenital retinal
      macrovessel is unknown. The diagnosis is clinical; its course is characterized by
      its stability. Its combination with central serous retinopathy is a fortuitous
      coincidence more than an individualized clinical form.

PMID- 20692720
TI  - [Facial necrotizing fasciitis after mild trauma of the eyelid: role of
      nonsteroidal anti-inflammatory treatment].
AB  - Facial necrotizing fasciitis is a rare but potentially serious and fatal
      infection, especially in children. We report the case of a five-year-old girl who
      developed rapidly progressive necrotizing fasciitis of the face secondary to a
      mild trauma, with a small wound in the upper eyelid. She had received
      nonsteroidal anti-inflammatory treatment before she was referred to our hospital.
      Despite surgical debridement of necrotic tissues and intravenous antibiotic
      therapy, recurrence occurred. Final progression was satisfactory without
      sequelae. We discuss here the role of nonsteroidal anti-inflammatory drugs in the
      development of necrotizing fasciitis in cutaneous lesions, whether traumatic or
      not.

PMID- 20692721
TI  - [Central retinal vein and artery occlusions related to intraocular involvement of
      an anaplastic optochiasmatic glioma].
AB  - Malignant optic tract gliomas are very aggressive and extremely rare tumors
      progressing to blindness and death in a few months. We report here the case of a
      73-year-old patient who presented a sudden decrease in visual acuity in his left
      eye associated with papilledema and headache: it revealed an optochiasmatic
      anaplastic glioma. A few months later, the glioma had grown, with infiltration of
      the right optic nerve and right peripapillary intraocular invasion. Through this
      case, we discuss the importance of achieving imaging for atypical optic
      neuropathies and stress the exceptional nature of intraocular invasion by a
      glioma.

PMID- 20692722
TI  - Obesity and psoriasis: from the Medical Board of the National Psoriasis
      Foundation.
AB  - An association between obesity and psoriasis has been reported. For a variety of
      reasons, obese persons with psoriasis are often more difficult to treat. We
      sought to review the literature on obesity and psoriasis and to discuss efficacy
      and safety data that could be utilized by clinicians who are making treatment
      decisions for obese persons with psoriasis. We performed a literature review
      using the terms "obesity and psoriasis" and "metabolic syndrome and psoriasis."
      Evidence from relevant literature was evaluated and categorized according to the
      criteria of Shekelle et al (published 1999). Numerous reports cite an association
      between obesity and psoriasis. When compared with non-obese patients with
      psoriasis, obese patients with psoriasis are more likely to experience certain
      adverse effects to medications and are less likely to respond favorably to
      systemic therapies. The amount of category I evidence for objectively determining
      the best treatment choices for obese patients with psoriasis was scarce and thus
      did not allow for the development of a treatment algorithm that could be
      generally applied for all psoriasis patients who are obese. Efficacy and safety
      concerns affected by obesity are important considerations for clinicians who are
      making decisions on proper treatment of psoriasis.

PMID- 20692723
TI  - Effect of intravenous immunoglobulin with or without cytotoxic drugs on pemphigus
      intercellular antibodies.
AB  - BACKGROUND: Intravenous immunoglobulin (IVIg)--a relatively new approach to treat
      pemphigus--lowers serum levels of pemphigus antibodies; however, the optimal way
      to use this agent is unknown. OBJECTIVE: We sought to examine whether
      coadministration of a cytotoxic drug to patients with pemphigus improves the
      ability of IVIg to decrease serum levels of intercellular (IC) antibodies.
      METHODS: In this retrospective study, we analyzed changes in IC antibody levels
      in 20 patients with pemphigus who were treated with 24 courses of IVIg
      administered alone (n = 10) or with a cytotoxic drug (n = 14). Each course of
      IVIg consisted of 400 mg/kg daily of immunoglobulin given over 5 days every other
      week; this cycle was repeated 3 to 4 times. Serum levels of IC antibodies were
      measured at baseline, before treatment, and 1 week and 1 month after the last
      IVIg cycle. RESULTS: One week after the last IVIg cycle IC antibodies decreased
      by an average of 77% in the group treated with IVIg and cytotoxic drug compared
      with 48% in the group treated with IVIg alone (P = .54), and by 90% versus 43% 1
      month later (P = .03). LIMITATIONS: A larger sample size is suggested for future
      studies. CONCLUSIONS: These observations confirm that IVIg can rapidly lower
      serum levels of autoantibodies in patients with pemphigus and its ability to do
      so is improved by the coadministration of a cytotoxic drug. These findings imply
      that the clinical effectiveness of IVIg in treating pemphigus, and possibly other
      autoantibody-mediated diseases, may be improved by the concurrent administration
      of a cytotoxic drug.

PMID- 20692724
TI  - Safety of retinyl palmitate in sunscreens: a critical analysis.

PMID- 20692725
TI  - A pilot study of emollient therapy for the primary prevention of atopic
      dermatitis.
AB  - BACKGROUND: Prevention strategies in atopic dermatitis (AD) using allergen
      avoidance have not been consistently effective. New research reveals the
      importance of the skin barrier in the development of AD and possibly food allergy
      and asthma. Correcting skin barrier defects from birth may prevent AD onset or
      moderate disease severity. OBJECTIVE: We sought to determine the feasibility of
      skin barrier protection as a novel AD prevention strategy. METHODS: We enrolled
      22 neonates at high risk for developing AD in a feasibility pilot study using
      emollient therapy from birth. RESULTS: No intervention-related adverse events
      occurred in our cohort followed up for a mean time of 547 days. Of the 20
      subjects who remained in the study, 3 (15.0%) developed AD, suggesting a
      protective effect when compared with historical controls. Skin barrier
      measurements remained within ranges seen in normal-appearing skin. LIMITATIONS:
      No conclusions regarding efficacy can be made without a control group.
      CONCLUSIONS: Skin barrier repair from birth represents a novel and feasible
      approach to AD prevention. Further studies are warranted to determine the
      efficacy of this approach.

PMID- 20692726
TI  - Infectious agents in cutaneous T-cell lymphoma.
AB  - Infectious agents have long been suspected as potential causative agents in
      cutaneous T-cell lymphoma (CTCL). Tissues of patients with CTCL have been
      evaluated for evidence of infection with a number of agents, including
      Staphylococcus aureus, retroviruses, and herpesviruses. These studies have failed
      to reveal a consistent association of CTCL with investigated agents. However,
      there is substantial evidence suggesting a potential role of a yet unidentified
      virus in CTCL. This article will review the findings of studies exploring
      potential roles of infectious agents in CTCL. In addition, we investigated CTCL
      tissues for evidence of infection with Merkel cell polyomavirus, a novel
      polyomavirus that was recently discovered as a probable carcinogenic agent in
      Merkel cell carcinoma. Cutaneous lesions demonstrating mycosis fungoides were
      stained with a monoclonal antibody against the Merkel cell polyomavirus T
      antigen, along with appropriate positive and negative controls.
      Immunohistochemical stains produced negative results in all examined mycosis
      fungoides specimens. These findings, which suggest a lack of association of CTCL
      with Merkel cell polyomavirus, add to the current body of knowledge regarding
      infectious agents and CTCL.

PMID- 20692727
TI  - Point prevalence surveys of healthcare-associated infection in 13 hospitals in
      Hubei Province, China, 2007-2008.
AB  - Successive point prevalence surveys were conducted in November 2007 and 2008 to
      monitor the prevalence of healthcare-associated infection (HCAI) in 13 grade III,
      1st class hospitals in Hubei Province of China, using the case definition
      criteria established by the Ministry of Health in the People's Republic of China.
      In total, of 20 350 patients surveyed, 833 (4.09%) HCAIs were observed in 790
      (3.88%) patients. There was no significant difference between the overall
      prevalence of HCAI in 2007 (4.14%) and 2008 (3.72%). Respiratory tract infection
      was the most common HCAI (63.15%), followed by surgical site infection (9.60%)
      and urinary tract infection (8.64%). Only 35.29% (294/833) of HCAI patients had
      positive microbiology results. Gram-negative bacteria were isolated most
      frequently and the most frequent organism was Pseudomonas aeruginosa, followed by
      Escherichia coli, Acinetobacter baumannii and Staphylococcus aureus. Antibiotic
      use was documented for 10,344 (50.83%) patients, and cephalosporins, penicillins,
      and quinolones were the most commonly used agents for treatment or prophylaxis.

PMID- 20692728
TI  - Stethoscope or 'Staphoscope'? Infection by auscultation.

PMID- 20692729
TI  - Two sequential outbreaks caused by multidrug-resistant Acinetobacter baumannii
      isolates producing OXA-58 or OXA-72 oxacillinase in an intensive care unit in
      France.

PMID- 20692730
TI  - [Red blood cell transfusion increases tissue oxygenation and improves the
      clinical outcome (pro)].

PMID- 20692731
TI  - Current management of biliary complications after liver transplantation: emphasis
      on endoscopic therapy.
AB  - Biliary complications occur in 5-25% of patients after liver transplantation and
      represent a major source of morbidity in this group of individuals. The major
      risk factor for most of these complications is ischemia of the bile tree usually
      due to obstruction or vascular insufficiency of the hepatic artery. The most
      common complications include biliary strictures (anastomostic and
      nonanastomotic), bile leaks, and biliary filling defects. The initial diagnostic
      approach starts with a high index of suspicion along with an abdominal ultrasound
      and Doppler exam. Magnetic resonance imaging is highly sensitive and is usually
      reserved for confirmation. The vast majority of these complications can be
      successfully treated with endoscopic retrograde cholangiography, however if this
      procedure cannot be performed a percutaneous approach or surgery is recommended.
      Nonanastomotic strictures and living donor recipients present a less favorable
      response to endoscopic management. This review focuses on the current diagnostic
      and therapeutic approaches for the management of biliary complications after
      liver transplantation.

PMID- 20692732
TI  - [Anemia in the elderly].
AB  - Anemia is a common disorder in the elderly and is associated with increased
      morbidity and mortality. In elderly subjects, in whom anemia is highly prevalent,
      there are several aspects, such as a hemoglobin at a level which should concern
      us limit, or identifying its causes, that are not easy to establish. This review
      focuses on knowing what is considered to be normal hemoglobin levels in adults
      and the common causes and potential consequences of anemia in elderly patients.
      It provides a diagnostic algorithm and an approach to treatment that addresses
      new treatments such as parenteral iron drugs and erythropoiesis-stimulating
      agents.

PMID- 20692733
TI  - [Frailty: from the epidemiology to the clinic].

PMID- 20692734
TI  - [False positive in the detection of ectopic gastric mucosa in the (99m)Tc
      pertechnetate abdominal scintigraphy].

PMID- 20692735
TI  - [Vibrio fluvialis diarrhoea in an HIV infected patient].

PMID- 20692737
TI  - Roscovitine-based CDK inhibitors acting as N-donor ligands in the platinum(II)
      oxalato complexes: preparation, characterization and in vitro cytotoxicity.
AB  - The reactions of potassium bis(oxalato)platinate dihydrate with two molar
      equivalents of the potent adenine-based cyclin-dependent kinase inhibitor 2-(1
      ethyl-2-hydroxyethylamino)-N6-(benzyl)-9-isopropyladenine (Roscovitine; Ros) and
      its benzyl-substituted analogues, i.e. 2-(1-ethyl-2-hydroxyethylamino)-N6-(2
      methoxybenzyl)-9-isopropyladenine (2OMeRos), 2-(1-ethyl-2-hydroxyethylamino)-N6
      (3-methoxybenzyl)-9-isopropyladenine (3OMeRos) and 2-(1-ethyl-2
      hydroxyethylamino)-N6-(4-methoxybenzyl)-9-isopropyladenine (4OMeRos), were
      performed and the [Pt(ox)(Ros)(2)].(3/4)H(2)O (1), [Pt(ox)(2OMeRos)(2)].H(2)O
      (2), [Pt(ox)(3OMeRos)(2)].(1/2)H(2)O (3) and [Pt(ox)(4OMeRos)(2)].(3/4)H(2)O (4)
      platinum(II) oxalato complexes were obtained. The methods of the elemental
      analysis, IR, Raman and NMR spectroscopy, ESI + mass spectrometry, molar
      conductivity measurement and TG/DTA thermal analysis were performed to
      characterize the obtained products. The complexes 1-4 involve tetracoordinated
      central Pt(II) atom with one bidentate-coordinated oxalate dianion (ox) and two
      monodentate adenine-based molecules (nRos), thus giving the square-planar
      geometry around the metal centre with a PtN(2)O(2) donor set. In vitro cytotoxic
      activity of the complexes against ovarian carcinoma (A2780), cisplatin resistant
      ovarian carcinoma (A2780cis), malignant melanoma (G-361), lung carcinoma (A549),
      cervix epitheloid carcinoma (HeLa), breast adenocarcinoma (MCF7) and osteosarcoma
      (HOS) human cancer cell lines was evaluated. All the tested complexes exceeded
      the in vitro cytotoxicity of cisplatin and oxaliplatin against HeLa, A2780cis
      and, except for 2, also against HOS cancer cells. The complex 1 was also tested
      for its cytotoxicity in primary cultures of human hepatocytes and it was not
      found to be hepatotoxic up to the concentration of 50.0 microM.

PMID- 20692739
TI  - Synthesis, characterization, interaction with DNA and cytotoxicity in vitro of
      novel pyridine complexes with Zn(II).
AB  - Four novel Zn(II) complexes [Zn(L(1))(bipy)(H(2)O)(2)].4H(2)O(1),
      [Zn(L(1))(phen)(H(2)O)(2)].4H(2)O(2), [Zn(L(2))(bipy)(H(2)O)(2)].4H(2)O(3) and
      [Zn(L(2))(phen)(H(2)O)(2)].4H(2)O (4), where bipy=2,2'-bipyridine, phen=1,10
      phenanthroline, L(1)=2,2'-bipyridine 5,5'-dicarboxylic acid, L(2)=2,2'-bipyridine
      4,4'-dicarboxylic acid, have been synthesized and characterized using IR, (1)H
      NMR, element analysis and single-crystal X-ray diffractometry. The unit cell
      parameters for the title complex (1), a=7.9621(10)A, b=12.6853(17)A,
      c=13.3714(17)A, alpha=68.549(2) degrees , beta=79.065(2) degrees ,
      gamma=88.723(2) degrees , V=1232.5(3)A(3), Z=15, space group,P-1(2).complex (4)
      a=9.5710(5)A, b=14.1140(7)A, c=19.0045(9)A, alpha=90 degrees , beta=99.9920(10)
      degrees , gamma=90 degrees , V=2528.3(2)A(3), Z=32, space group, P121/n 1(14).
      The binding of the complexes with fish sperm DNA (FS-DNA) was investigated by
      electronic absorption spectra and fluorescence spectroscopy, showing that the
      complexes have the ability of interaction with DNA of intercalative mode. The
      intrinsic binding constant K of the complexes with FS-DNA is 0.37 x 10(5)M(-1)
      (1) 0.73 x 10(5)M(-1) (2), 0.98 x 10(5)M(-1) (3), and 1.05 x 10(5)M(-1) (4). The
      results indicate that the four complexes bound to DNA with different binding
      affinity, in the order complex 4>3>2>1. Gel electrophoresis assay demonstrates
      the ability of the complexes to cleave the pBR322 plasmid DNA. The cytotoxic
      activity of the complexes was tested against four different cancer cell lines.
      The four complexes exhibited cytotoxic specificity and significant cancer cell
      inhibitory rate.

PMID- 20692738
TI  - Synthesis and activity of endomorphin-2 and morphiceptin analogues with proline
      surrogates in position 2.
AB  - The opioid agonists endomorphins (Tyr-Pro-Trp-Phe-NH(2); EM1 and Tyr-Pro-Phe-Phe
      NH(2); EM2) and morphiceptin (Tyr-Pro-Phe-Pro-NH(2)) exhibit an extremely high
      selectivity for mu-opioid receptor. Here a series of novel EM2 and morphiceptin
      analogues containing in place of the proline at position 2 the S and R residues
      of beta-homologues of proline (HPro), of 2-pyrrolidinemethanesulphonic acid
      (HPrs) and of 3-pyrrolidinesulphonic acid (betaPrs) have been synthesized and
      their binding affinity and functional activity have been investigated. The
      highest micro-receptor affinity is shown by [(S)betaPrs(2)]EM2 analogue (6e)
      which represents the first example of a beta-sulphonamido analogue in the field
      of opioid peptides.

PMID- 20692740
TI  - Synthesis and evaluation of fatty acyl ester derivatives of cytarabine as anti
      leukemia agents.
AB  - Cytarabine is a chemotherapeutic agent predominately used for the treatment of
      acute myeloid leukemia and lymphoblastic leukemia. Cytarabine is a polar
      nucleoside, has a short plasma half-life, and its use is associated with severe
      side effects. Fatty acyl derivatives of cytarabine were synthesized with the
      expectation to improve cellular uptake and generate derivatives with a longer
      duration of action. Multi-step protection and deprotection reactions of hydroxyl
      and amino groups and conjugation with a fatty acid (i.e., myristic acid and 12
      thioethyldodecanoic acid) afforded 5'-O-substituted, 2'-O-substituted, and 2',5'
      disubstituted fatty acyl derivatives of cytarabine. 2',5'-Dimyristoyl derivative
      of cytarabine was found to inhibit the growth of CCRF-CEM cells by approximately
      76% at concentration of 1 microM after 96 h incubation.

PMID- 20692741
TI  - Synthesis and anticancer activity of 5-(3-indolyl)-1,3,4-thiadiazoles.
AB  - A series of 5-(3-indolyl)-2-substituted-1,3,4-thiadiazoles 5a-m were synthesized
      and their cytotoxicity analyzed against six human cancer cell lines. The reaction
      of indole-3-carboxylic acid 3 with aryl or heteroaryl hydrazides afforded the
      N,N'-diacylhydrazines 4, which upon treatment with Lawesson's reagent resulted in
      the formation of indolyl-1,3,4-thiadiazoles 5a-m in good yields. Indolyl-1,3,4
      thiadiazole 5m with 4-benzyloxy-3-methoxyphenyl and 5-bromo indolyl substituents
      is the most active in suppressing the growth of cancer cells (IC(50) 1.5 muM,
      PaCa2). The compounds 5b, 5e and 5h bearing C-2 substituent as benzyl, 3,4
      dimethoxyphenyl and 4-benzyloxy-3-methoxyphenyl, respectively, have shown
      significant cytotoxicity against multiple cancer cell lines. Introduction of 4
      dimethylamino (5d and 5k) and 3,4,5-trimethoxy (5l) groups in the C-2 phenyl ring
      induced selectivity against MCF7 and MDA-MB-231 cancer cell lines (compounds 5d,
      5k and 5l).

PMID- 20692742
TI  - The relationship between birth unit design and safe, satisfying birth: developing
      a hypothetical model.
AB  - Recent advances in cross-disciplinary studies linking architecture and
      neuroscience have revealed that much of the built environment for health-care
      delivery may actually impair rather than improve health outcomes by disrupting
      effective communication and increasing patient and staff stress. This is also
      true for maternity care provision, where it is suggested that the design of the
      environment can also impact on the experiences and outcomes for birthing women.
      The aim of this paper is to describe the development of a conceptual model based
      on literature and understandings of design, communication, stress and model of
      care. The model explores potential relationships among a set of key variables
      that need to be considered by researchers wishing to determine the
      characteristics of optimal birth environments in relation to birth outcomes for
      women and infants. The conceptual model hypothesises that safe satisfying birth
      is reliant on the level of stress experienced by a woman and the staff around
      her, stress influences the quality of communication with women and between staff,
      and this process is mediated by the design of the birth unit and model of care.
      The conceptual model is offered as a starting point for researchers who have an
      appreciation of the complexity of birth and the ability to bring together
      colleagues from a range of disciplines to explore the pre-requisites for safe and
      effective maternity care in new ways.

PMID- 20692743
TI  - How midwives' discursive practices contribute to the maintenance of the status
      quo in English maternity care.
AB  - BACKGROUND: poor relationships between maternity care professionals still
      contribute to poor outcomes for childbearing women, although issues concerning
      power, gender, professionalism and the medicalisation of birth have been
      identified and discussed as germane to this situation for nearly three decades.
      Although power relationships and communication issues are known to affect the way
      maternity care professionals in the UK work together, there has been no study of
      the interplay between these factors, or of how semiotic aspects of professionals'
      communication relate to it. AIM: to explore how National Health Service midwives'
      discursive practices relate to the status quo; that is, how they contribute
      either to maintaining or challenging traditional discourses concerning power,
      gender, professionalism and the medicalisation of birth. METHOD: in a qualitative
      study within a critical discourse analysis framework, data were collected from
      maternity care professionals and women within one English maternity unit, through
      semi-structured interviews and observation of physical behaviour and naturally
      occurring conversation. FINDINGS: midwives in the unit revealed an inconsistent
      professional identity, sometimes challenging established hierarchies and power
      relationships, but often reinforcing traditional notions of gender,
      professionalism and the medicalisation of birth through their discursive
      practices. CONCLUSIONS: given the known effect of wider social factors on
      maternity care, it is not surprising that the status quo persists, and that
      problems linked to these factors are still commonplace. This situation is
      compounded by the conflicting obligations under which UK midwives are forced to
      practice. These findings may have implications for midwives' capacity to respond
      to current challenges facing the profession.

PMID- 20692744
TI  - A community-based participatory research approach to explore community
      perceptions of the quality of maternal-newborn health services in the Dominican
      Republic.
AB  - OBJECTIVE: to understand both men's and women's beliefs and attitudes regarding
      public maternity and newborn services, care and quality. DESIGN: qualitative,
      cross-sectional, retrospective study with an observation arm, using community
      based participatory research as both the mechanism of enquiry and catalyst for
      change. SETTING: four urban neighbourhoods in the Dominican Republic, selected in
      collaboration with the Provincial Medical Public Health Director and the
      partnering local public hospital. PARTICIPANTS: adolescent women (15-20 years of
      age), adult women (21-49 years of age) and adult men (>19 years of age) from the
      four neighbourhoods were recruited to participate in focus sessions, personal
      interviews and/or antenatal observations. A total number of 137 participants were
      recruited: 27 males, 51 adolescent females and 59 adult females. The attrition
      rate was 17% (n=23). Dominican and US midwives and nurses, as well as community
      leaders, comprised the research team. MEASUREMENTS AND FINDINGS: following
      informed consent, self-reported demographics and obstetric history were
      collected. Twelve focus groups and 12 individual interviews were recorded and
      transcribed, then qualitatively analysed for content and interpretation of
      salient themes. Antenatal observations were performed by community leaders to
      identify patterns of antenatal health-care delivery and utilisation. The main
      over-riding theme uncovered by the research was 'no me hace caso', or that women
      and men accessing the maternal health system did not feel valued. The significant
      amount of time required to receive care was interpreted by the participants as a
      lack of respect. Finally, the idea of 'cuna' emerged, in which participants noted
      special treatment for those with social connections to health-care providers.
      Presentation to the hospital was challenging but resulted in hospital volunteers
      joining the community volunteer group to collaborate on improving services. KEY
      CONCLUSIONS AND IMPLICATIONS: this study, conducted in the Dominican Republic,
      illustrates international collaboration between university researchers, maternity
      service providers and community members. Community-based participatory research
      may be an effective mechanism to unite community members and health providers in
      the common mission to improve maternal-newborn health services.

PMID- 20692745
TI  - Knee biomechanics during walking gait following matrix-induced autologous
      chondrocyte implantation.
AB  - BACKGROUND: Matrix-induced autologous chondrocyte implantation is a technique for
      repairing articular cartilage defects in the knee. Despite reported improvements
      in pain, little is known about the recovery of knee biomechanics during walking
      gait. METHODS: A randomized controlled study design was used to investigate knee
      biomechanics during gait in 61 patients following matrix-induced autologous
      chondrocyte implantation, in conjunction with either 'accelerated' or
      'traditional' approaches to post-operative weight-bearing rehabilitation. Gait
      analysis was performed at 3, 6 and 12 months post-surgery in both patient groups,
      and two matched, unaffected control groups for comparison. FINDINGS: The
      spatiotemporal and ground reaction force parameters were similar between patient
      groups and their respective control groups at all time points. When compared with
      controls, both patient groups demonstrated significantly reduced knee extension
      moments up until, and including, 12 months. The traditional group demonstrated a
      significantly reduced knee adduction moment at 3, 6 and 12 months, and a
      significantly reduced knee flexion moment at 3 months. There were no differences
      in these knee moments between the accelerated patient group and controls.
      INTERPRETATION: Overall, a higher level of gait dysfunction was observed in
      patients who underwent traditional rehabilitation. Future research is needed to
      investigate the recovery of normal gait following matrix-induced autologous
      chondrocyte implantation, and its effect on repair tissue development.

PMID- 20692746
TI  - Experimental calf muscle pain attenuates the postural stability during quiet
      stance and perturbation.
AB  - BACKGROUND: The purpose of this study was to evaluate how acute pain changes the
      postural control and stability during quiet standing and after unexpected
      perturbations. METHODS: Nine subjects stood as quiet as possible on a movable
      force platform that recorded the centre of pressure position and provided
      unexpected floor perturbations, before, during and after experimental calf muscle
      pain. Bilateral surface electromyography from the tibialis anterior and medial
      gastrocnemius muscles was recorded. The foot pressure distributions were measured
      using pressure insoles. Intramuscular injections of hypertonic saline were
      administrated (right leg) to induce acute pain in the tibialis anterior and/or
      medial gastrocnemius muscles, and an isotonic injection was used as control.
      FINDINGS: Simultaneous pain in tibialis anterior and medial gastrocnemius altered
      the postural control. During quiet standing: higher medial-lateral centre of
      pressure speed and increased total sway displacement (P<0.05), weight moved to
      the non-painful side, (P<0.05) and plantar centre of pressure of the left foot
      was shifted towards the heel's direction (P<0.05). During forward perturbation:
      higher mean displacement in the medial-lateral direction (P<0.05). After the
      perturbation: larger sway area (P<0.05). Pain only in the medial gastrocnemius
      muscle increased medial-lateral centre of pressure speed (P<0.05) during the
      quiet standing. Pain only in the tibialis anterior muscle increased peak pressure
      on the contralateral foot (P<0.05). INTERPRETATION: These findings suggest that
      large acute painful areas on the calf muscles impair the postural control and
      potentially increase the risk factors for falls. Further strategies aiming to
      reduce pain in patients may lead to improvement in balance.

PMID- 20692747
TI  - Multidimensional modeling of aerosol monitoring data.
AB  - The present study deals with the application of N-way factor analysis for
      modeling and interpretation of a three-dimensional environmental data set
      acquired from monitoring of particulate matter (PM) collected at four different
      sampling locations in Lower Austria region (Central Europe). In the study the
      Tucker3 algorithm for N-way modeling was used. It was statistically validated
      that the Tucker3 model offered having the dimensionality [222] is appropriate for
      correct interpretation of the relationships between chemical parameters, sampling
      locations and sampling period. The Tucker3 model allowed to distinguish three
      major sources of pollution in the region of interest conditionally named "soil
      dust", "combustion" and "street dust" latent factors as responsible for chemical
      profile of PM and to identify seasonal variability. Additionally, some
      specificity of the sampling locations was also pointed out.

PMID- 20692748
TI  - Distribution and sources of polyfluoroalkyl substances (PFAS) in the River Rhine
      watershed.
AB  - The concentration profile of 40 polyfluoroalkyl substances (PFAS) in surface
      water along the River Rhine watershed from the Lake Constance to the North Sea
      was investigated. The aim of the study was to investigate the influence of point
      as well as diffuse sources, to estimate fluxes of PFAS into the North Sea and to
      identify replacement compounds of perfluorooctane sulfonate (PFOS) and
      perfluorooctanoic acid (PFOA). In addition, an interlaboratory comparison of the
      method performance was conducted. The PFAS pattern was dominated by
      perfluorobutane sulfonate (PFBS) and perfluorobutanoic acid (PFBA) with
      concentrations up to 181 ng/L and 335 ng/L, respectively, which originated from
      industrial point sources. Fluxes of SigmaPFAS were estimated to be approximately
      6 tonnes/year which is much higher than previous estimations. Both, the River
      Rhine and the River Scheldt, seem to act as important sources of PFAS into the
      North Sea.

PMID- 20692749
TI  - Comparison of multifrequency bioelectrical impedance analysis and dual-energy X
      ray absorptiometry assessments in outpatient hemodialysis patients.
AB  - BACKGROUND: Malnutrition is common in hemodialysis patients and closely related
      to increased morbidity and mortality. As such, simple, reliable, and easily
      available methods of determining nutritional status and recognition of short-term
      changes in body composition are desirable for routine clinical practice. STUDY
      DESIGN: Diagnostic test study. SETTING & PARTICIPANTS: 53 stable adult
      hemodialysis patients attending for thrice-weekly outpatient hemodialysis in a
      university tertiary hospital dialysis center. INDEX TEST: Comparison of dual
      energy x-ray absorptiometry (DEXA) and multifrequency bioelectrical impedance
      analysis (BIA) using a tetrapolar 8-point tactile electrode system as 2 index
      tests of body composition. REFERENCE TEST: None. RESULTS: Assessment of whole
      body composition showed that lean body mass measured using the 2 techniques
      correlated highly, with good method agreement shown using a Bland-Altman plot (r
      = 0.92; P < 0.001; bias, +1 g [95% CI, -1,173 to 1,175]), as did fat mass (r =
      0.93; P < 0.001; bias, -157 g [95% CI, -1,251 to 937]). Similarly, segmental
      analysis of lean body mass showed strong correlations between lean body mass of
      the trunk and right and left legs with small bias (r = 0.85, 0.89, and 0.86,
      respectively; P < 0.001; Bland-Altman bias, -859, +364, and +552 g,
      respectively), but weaker correlations for lean body mass for the right and left
      arm (r = 0.69 and 0.75, respectively; P < 0.001; Bland-Altman bias, -240 and +12
      g, respectively). Bone mineral content derived using multifrequency BIA
      overestimated that measured using DEXA (r = 0.77; P < 0.001; bias, +530 g [95%
      CI, 422-638]). LIMITATIONS: Retrospective study in a healthy ambulant outpatient
      cohort. CONCLUSIONS: Compared with DEXA, multifrequency BIA appears to be a
      robust tool for measuring and monitoring total-body fat and lean body mass in
      hemodialysis patients; however, there is less agreement in bone mineral content
      assessment between the 2 methods.

PMID- 20692750
TI  - Factors associated with kidney disease progression and mortality in a referred
      CKD population.
AB  - BACKGROUND: Knowing how kidney disease progresses is important for decision
      making in patients with chronic kidney disease (CKD) and for designing clinical
      services. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: We
      examined renal function trajectories in CRISIS (Chronic Renal Insufficiency
      Standards Implementation Study), in which 1,325 patients with CKD stages 3-5 and
      mean age of 65.1 years were followed up prospectively for a median of 26 months
      after referral to a regional nephrology center in the United Kingdom. By
      protocol, estimated glomerular filtration rate was determined every 12 months.
      PREDICTORS: CKD stage defined as estimated glomerular filtration rate >= 45
      (stage 3a), 30-44 (3b), 15-29 (4), and < 15 (5) mL/min/1.73 m2. OUTCOMES: Onset
      of renal replacement therapy (RRT), death, the composite end point of RRT or
      death, or decreasing CKD stage. RESULTS: During a median follow-up of 26 months,
      13% reached the end point of RRT (5.1 events/100 patient-years), 20% died (9.6
      deaths/100 patient-years), and 33% reached the combined end point of RRT or death
      (14.7 events/100 patient-years). For stage 3a, baseline prevalence and annual
      probabilities of decreasing CKD stage, RRT, and death were 18.0%, 0.41, 0.01, and
      0.02, respectively. Corresponding values for stage 3b were 32.5%, 0.22, < 0.01,
      and 0.06; for stage 4, 36.5%, 0.17, 0.03, and 0.10; and for stage 5, 13.2%, zero
      (by definition), 0.31, and 0.08, respectively. Markov model projections suggested
      a steady decrease for proportions with stages 3a, 3b, and 4; a steady increase
      for death and RRT; and a biphasic pattern for (non-RRT) stage 5, with a plateau
      in the first 2 years followed by a steady decrease. LIMITATIONS: Single-center
      observational study. CONCLUSION: This study suggests that death and RRT are the
      dominant outcomes in patients referred for management of CKD and that most
      patients spend comparatively little time in late stages without RRT.

PMID- 20692751
TI  - Donor exchange programs in kidney transplantation: rationale and operational
      details from the north central donor exchange cooperative.
AB  - The increasing need for kidney transplants has led to innovations such as donor
      exchange programs. These programs offer transplant recipients with incompatible
      donors an opportunity to receive a compatible kidney. They also provide an
      alternative to costly desensitization protocols that have unproven long-term
      outcomes. Donor exchange programs have multiple options, including simple 2-pair
      exchanges, more complicated domino exchanges, or chain donations. The United
      States currently is limited by regional programs that provide for kidney donor
      exchanges. However, with the increasing public interest in and need for kidney
      transplants, general nephrologists will be approached with questions about these
      donor exchange programs. The goal of this review is to discuss donor exchange
      programs, including their role in expanding the donor pool, various types of
      exchanges, regional centers that provide these programs, and the process involved
      in patient enrollment. General knowledge of donor exchange programs will help
      providers in discussing options with patients approaching end-stage kidney
      disease and transplant.

PMID- 20692752
TI  - Kidney function, albuminuria, and all-cause mortality in the REGARDS (Reasons for
      Geographic and Racial Differences in Stroke) study.
AB  - BACKGROUND: Chronic kidney disease and albuminuria are associated with increased
      risk of all-cause mortality. STUDY DESIGN: Prospective observational cohort
      study. SETTING & PARTICIPANTS: 17,393 participants (mean age, 64.3 +/- 9.6 years)
      in the REGARDS (Reasons for Geographic and Racial Differences in Stroke) Study.
      PREDICTOR: Estimated glomerular filtration rate (eGFR), urinary albumin
      creatinine ratio (ACR). OUTCOME: All-cause mortality (710 deaths); median
      duration of follow-up, 3.6 years. MEASUREMENTS & ANALYSIS: Categories of eGFR (90
      to <120, 60 to <90, 45 to <60, 30 to <45, and 15 to <30 mL/min/1.73 m(2)) and
      urinary ACR (<10 mg/g or normal, 10 to <30 mg/g or high normal, 30 to 300 mg/g or
      high, and >300 mg/g or very high). Cox proportional hazards models were adjusted
      for demographic factors, cardiovascular covariates, and hemoglobin level.
      RESULTS: The background all-cause mortality rate for participants with normal
      ACR, eGFR of 90 to <120 mL/min/1.73 m(2), and no coronary heart disease was 4.3
      deaths/1,000 person-years. Higher ACR was associated with an increased
      multivariable-adjusted HR for all-cause mortality within each eGFR category.
      Decreased eGFR was associated with a higher adjusted HR for all-cause mortality
      for participants with high-normal (P = 0.01) and high (P < 0.001) ACRs, but not
      those with normal or very high ACRs. LIMITATIONS: Only 1 laboratory assessment
      for serum creatinine and ACR was available. CONCLUSIONS: Increased albuminuria
      was an independent risk factor for all-cause mortality. Decreased eGFR was
      associated with increased mortality risk in those with high-normal and high ACRs.
      The mortality rate was low in the normal-ACR group and increased in the very-high
      ACR group, but did not vary with eGFR in these groups.

PMID- 20692754
TI  - Swimming upstream? Taking action on the social determinants of health
      inequalities.

PMID- 20692753
TI  - Do Mexican immigrants "import" social gradients in health to the US?
AB  - Greater educational attainment is consistently associated with lower mortality
      and better health, a pattern known as the social gradient. However, recent
      research suggests that Mexican-origin adults in the US have weak or flat
      gradients, in contrast to steep gradients for non-Hispanic whites. In this study
      we evaluate one hypothesis for this finding: Is the relative weakness of
      education gradients in health behaviors observed among Mexican-origin adults in
      the US due to weak gradients in the sending population? We test this "imported
      gradients" hypothesis with data from two nationally-representative datasets: the
      US National Health Interview Survey (NHIS) and the Mexican National Health Survey
      (ENSA 2000). We compare education gradients in smoking and obesity for recently
      arrived Mexican immigrants in the US to the corresponding gradients in high
      migration regions of Mexico. Results partially support the imported gradients
      hypothesis and have implications for health education and promotion programs
      targeted to immigrant populations to reduce racial and ethnic disparities in
      health in the US.

PMID- 20692755
TI  - Rising up with shoe leather? A comment on Fair Society, Healthy Lives (the Marmot
      Review).

PMID- 20692756
TI  - A new approach to global health institutions? A case study of new vaccine
      introduction and the formation of the GAVI Alliance.
AB  - There is an emerging research agenda to analyse empirically the forces driving
      changes in global health governance. This study applies analytical tools from
      international relations research to explain the formation of international health
      regimes. The study utilizes two explanatory perspectives: individual leadership,
      and the interests of key non-state actors in the formation process, using the
      case of the formation of the Global Alliance for Vaccines and Immunization (GAVI)
      from 1995 to 1999. The case study is based on material from interviews with key
      actors, an archival review of documents from the Children's Vaccine Initiative
      (CVI), and published literature. Findings show that the regime formation process
      was initiated by individuals who were primarily affiliated to scientific
      communities and who led to the World Bank and the Gates Foundation becoming
      champions of a new coordinating mechanism for new vaccine introduction.
      Negotiations in the regime formation process were between a small group of
      founding agencies with divergent interests regarding immunization priorities. The
      case also sheds light on the authority of the WHO and the resources of the Gates
      Foundation in driving the process towards the final structure of the alliance.
      The paper discusses the potential contribution of the international relations
      approach compared to policy research as a way of understanding the institutional
      dynamics of global health, particularly in respect of relations between countries
      and non-state actors.

PMID- 20692758
TI  - [Descending necrotizing mediastinitis].

PMID- 20692757
TI  - Factors associated with the perpetration of sexual violence among wine-shop
      patrons in Chennai, India.
AB  - With an estimated 2.5 million people living with HIV/AIDS, India has the third
      highest number of HIV-infected people in the world. Despite reductions in
      prevalence among the general population, the percentage of all infections
      occurring among Indian women is continuing to rise. Women's risk of HIV infection
      from their partner and observed associations between sexual violence and HIV
      infection in India underscore the importance of understanding determinants of
      forced sex. A probability survey was conducted from June 2003 to August 2007 in
      Chennai, India, among alcohol venue ("wine shops") patrons to estimate the
      prevalence of sexual violence and to identify risk factors associated with
      perpetrating forced sex. Among 1499 men, 28.5% reported forced sex with at least
      one partner in the past 3 months. In multivariate analysis, earning income for
      less than 12 months a year, visiting the wine shop with friends, STD symptoms,
      perpetration of physical violence, and number of sexual partners were
      statistically significantly associated with perpetrating forced sex. Men who
      reported having 3 or more close friends were less likely to perpetrate violence.
      HIV interventions that facilitate formal groups that foster positive social
      support and address a range of HIV risk behaviors including sexually and
      physically abusive behaviors are recommended to reduce sexual violence.

PMID- 20692759
TI  - [Diaphragmoplasty with patch on the hepatic hydrothorax due to pleuroperitoneal
      fistula].

PMID- 20692760
TI  - Traumatic pericardial effusion: impact of diagnostic and surgical approaches.
AB  - INTRODUCTION: In trauma patients with chest injuries, traumatic pericardial
      effusion is an important scenario to consider because of its close linkage to
      cardiac injury. Even with advances in imaging, diagnosis remains a challenge and
      use of which surgical approach is controversial. This study reviews the treatment
      algorithm, surgical outcomes, and predictors of mortality for traumatic
      pericardial effusion. PATIENTS AND METHODS: Information on demographics,
      mechanisms of trauma, injury scores, diagnostic tools, surgical procedures,
      associated injuries, and hospital events were collected retrospectively from a
      tertiary trauma center. RESULTS: Between June 2003 and December 2009, 31 patients
      (23 males and 8 females) with a median age of 31 (range 16-77), who had undergone
      surgical drainage of pericardial effusion were enrolled in the study. Blunt
      trauma accounted for 27 (87.1%) insults, and penetrating injury accounted for 4
      (12.9%). Patients were diagnosed by Focused Assessment with Sonography for Trauma
      (FAST) (8 patients), computerized tomography (7 patients), echocardiography (9
      patients), and incidentally during surgery (7 patients). Notably, sixteen (51.7%)
      patients required surgical repair for traumatic cardiac ruptures, including 6
      (19.6%) with pericardial defects who presented initially with hemothorax. The
      surgical approaches were subxiphoid in 8 patients (25.8%), thoracotomy in 7
      (22.6%), and sternotomy in 19 (61.2%), including 3 conversions from thoracotomy.
      The survival to discharge rate was 77.4% (24/31). Concomitant cardiac repair,
      associated pericardial defects, and initial surgical approach did not affect
      survival, but the need for massive transfusion, cardiopulmonary cerebral
      resuscitation (CPCR), trauma score, and incidental discovery at surgery all had a
      significant impact on the outcome. CONCLUSIONS: Precise diagnoses of traumatic
      pericardial effusions are still challenging and easily omitted even with FAST,
      repeat cardiac echo and CT. The number of patients with traumatic pericardial
      effusion requiring surgical repair is high. Standardized therapeutic protocol,
      different surgical approaches have not impact on survival. Correct
      identification, prompt drainage, and preparedness for concomitant cardiac repair
      seem to be the key to better outcomes.

PMID- 20692761
TI  - Improvements in fermentative biological hydrogen production through metabolic
      engineering.
AB  - Replacement of fossil fuels with alternative energies is increasingly imperative
      in light of impending climate change and fossil fuel shortages. Biohydrogen has
      several potential advantages over other biofuels. Dark fermentation as a means of
      producing biohydrogen is attractive since a variety of readily available waste
      streams can be used. However, at present its practical application is prevented
      by the low yields obtained. Here the basic metabolisms leading to hydrogen
      production are outlined and current research to increase yields, either through
      modification of existing pathways, or by metabolic engineering to create new,
      higher yielding, pathways, is discussed. Inactivation of competing reactions and
      manipulation of culture conditions has lead to higher hydrogen yields, near those
      predicted by metabolic schemes. However, to be useful, hydrogen production must
      be increased beyond present limits. Several possibilities for surpassing those
      limits using metabolic engineering are presented.

PMID- 20692763
TI  - Biological and photocatalytic treatment integrated with separation and reuse of
      titanium dioxide on the removal of chlorophenols in tap water.
AB  - We investigated biological, photocatalytic, and combination of biological and
      photocatalytic treatments in order to remove a mixture of 2-chlorophenol, 2,4
      dichlorophenol, 2,4,5-trichlorophenol, and pentachlorophenol in tap water (total:
      100 mg L(-1), each: 25 mg L(-1)). The removal of chlorinated phenols was
      conducted with a flow biological treatment and a circulative flow photocatalytic
      treatment under black light and sunlight irradiations integrated with titanium
      dioxide separation and reuse. The combined biological-photocatalytic treatment
      significantly shortened the degradation and mineralization time of both the
      biological treatment and the photocatalytic treatment. The removed chlorophenols
      per hour by the combined biological-photocatalytic treatment was 25.8 mg h(-1),
      whereas by the combined photocatalytic-biological treatment was 10.5 mg h(-1).
      After a large portion of biodegradable 2-chlorophenol and 2,4-dichlorophenol, and
      around half amount of slightly biodegradable 2,4,5-trichlorophenol were removed
      by the biological treatment, the remained three chlorophenols, biorecalcitrant
      pentachlorophenol, and biodegradation products were completely removed by the
      subsequent photocatalytic treatment. Since titanium dioxide particles in tap
      water spontaneously sedimented on standing after the photocatalytic treatment,
      the combined treatment can be operated by integrating with the titanium dioxide
      separation and reuse. The TiO(2) particles were recovered and reused at least
      three times without significantly decreasing the removal efficiency.

PMID- 20692762
TI  - Helicobacter pylori in the pathogenesis of gastric cancer and gastric lymphoma.
AB  - Chronic gastric infection by the gram-negative bacterium Helicobacter pylori is
      strongly associated with the development of distal gastric carcinoma and gastric
      mucosal lymphoma in humans. Eradication of H. pylori with combination antibiotic
      therapy cures most cases of gastric lymphoma and slows progression to gastric
      adenocarcinoma. H. pylori promotes gastric neoplasia, principally via the
      induction of an intense gastric inflammatory response that lasts over decades.
      This persistent inflammatory state produces chronic oxidative stress and adaptive
      changes in gastric epithelial and immune cell pathobiology that in a minority of
      infected subjects eventually proceeds to frank neoplastic transformation.

PMID- 20692764
TI  - Factorial design optimization of experimental variables in the on-line
      separation/preconcentration of copper in water samples using solid phase
      extraction and ICP-OES determination.
AB  - An on-line preconcentration procedure using solid phase extraction (SPE) for the
      determination of copper in different water samples by inductively coupled plasma
      optical emission spectrometry (ICP-OES) is proposed. The copper was retained on a
      minicolumn filled with ethyl vinyl acetate (EVA) at pH 8.0 without using any
      complexing reagent. The experimental optimization step was performed using a two
      level full factorial design. The results showed that pH, sample loading flow
      rate, and their interaction (at the tested levels) were statistically
      significant. In order to determine the best conditions for preconcentration and
      determination of copper, a final optimization of the significant factors was
      carried out using a central composite design (CCD). The calibration graph was
      linear with a regression coefficient of 0.995 at levels near the detection limit
      up to at least 300 MUg L(-1). An enrichment factor (EF) of 54 with a
      preconcentration time of 187.5 s was obtained. The limit of detection (3sigma)
      was 0.26 MUg L(-1). The sampling frequency for the developed methodology was
      about 15 samples/h. The relative standard deviation (RSD) for six replicates
      containing 50 MUg L(-1) of copper was 3.76%. The methodology was successfully
      applied to the determination of Cu in tap, mineral, river water samples, and in a
      certified VKI standard reference material.

PMID- 20692765
TI  - Treatment of VOCs with molecular sieve catalysts in regenerative catalytic
      oxidizer.
AB  - This work prepares molecular sieve catalysts with various metal species and
      various metal weight loadings by impregnation, and then screens them in a
      catalytic combustion system. The current study further investigates the molecular
      sieve catalyst in an RCO system after it performed well in combustion efficiency.
      This work tests its performances in terms of CO(2) yield, pressure drop, the
      difference between temperatures of the inlet and outlet gases (T(d)), and thermal
      recovery efficiency (TRE), with various operational conditions. Experimental
      results demonstrate that the 10 wt% Cu/(MS) catalyst was the most active because
      it has the greatest combustion efficiency to treat volatile organic compounds
      (VOCs) than Co/(MS) catalysts and Mn/(MS) catalysts. The 10 wt% Cu/(MS) catalyst
      used in an RCO system reaches over 95% CO(2) yields under the heating zone
      temperature (T(set))=400 degrees C, gas velocity (U(g))=0.37 m/s, isopropyl
      alcohol (IPA) concentration=200-400 ppm conditions. Moreover, the RCO system
      performed well in economic efficiency with the RCO with in terms of TRE, T(d) and
      pressure drop. The TRE ranged from 90.4% to 94.6% and T(d) ranged from 14.0 to
      34.2 degrees C under various conditions at T(set)=300-450 degrees C. Finally, the
      results of the stability test demonstrated that the catalyst was very stable at
      various U(g) values and various T(set) values.

PMID- 20692766
TI  - Anti-inflammatory treatment of Complex Regional Pain Syndrome.

PMID- 20692767
TI  - Angiostrongylus vasorum infection in dogs: Presentation and risk factors.
AB  - Infection with the nematode Angiostrongylus vasorum is an emerging cause of
      canine disease in Europe and part of North America, yet published data on its
      epidemiology in endemic areas are lacking. This study tested faecal samples from
      897 dogs attending veterinary practices in the southern part of Great Britain, a
      long standing endemic focus. Among 790 dogs presenting with respiratory or other
      signs broadly suggestive of angiostrongylosis, 16% tested positive on a single
      Baermann's examination, compared with 2% of healthy dogs in the same catchment
      areas. Risk factors for positive tests included age (higher risk in younger
      dogs), season (more cases earlier in the calendar year), and worming history
      (lower risk if given milbemycin oxime in the past 12 weeks). Sex, neutering
      status and breed were not significant in terms of risk of testing positive. The
      most common clinical signs in infected dogs were respiratory, along with non
      specific signs such as lethargy and exercise intolerance, while bleeding,
      neurological and gastrointestinal signs were also recorded. Around half the dogs
      sampled that showed signs of extra-pulmonary disease also had respiratory signs.
      Direct faecal smears and Baermann's tests read after one hour detected 56% and
      83% of diagnosed cases respectively. The data confirm that A. vasorum is commonly
      associated with disease in endemic areas, which manifests with a broad range of
      signs at primary care level. Information on risk factors is useful in diagnosis
      and control, and forms a basis for further epidemiological investigation.

PMID- 20692768
TI  - Audit of protocols for treatment of paediatric burns in emergency departments in
      the Ile de France.
AB  - INTRODUCTION: The main purpose of this study was to establish the existence and
      accuracy of protocols for treatment of children with burns in emergency
      departments (EDs) across the Ile de France. In addition, we also analysed the
      incidence of paediatric burns. METHODS: A postal questionnaire was sent to 91 EDs
      in the Ile de France. Data collected were: number of children with burns in 2005,
      the absence or presence of specific written protocols. The ED was asked to send a
      copy of the protocol for analysis. RESULTS: Forty-six EDs (50.5%) replied to the
      questionnaire. These EDs treated a total of 3258 children with burns,
      corresponding to 0.63% of paediatric pathologies in EDs. Amongst responding EDs,
      48% had specific written protocols for the management of children with burns (but
      only in the larger EDs: >10000 patient visits/year). A written protocol for
      managing pain in children was present in 65% of cases. For analgesia, 80% used
      oxygen/nitrous oxide. Concerning second-step analgesics, six EDs 67% used a
      combination of paracetamol/codeine and only 22% used non-steroidal antiflammatory
      drug. Regarding third-step analgesics, 67% used nalbuphine while only 43% used
      morphine. CONCLUSION: 3,200 children were registered with burns in half of the
      region's EDs during 2005 (0.63% of paediatric consultations). The larger the ED
      the higher was the availability of specific written protocols. International
      recommendations appeared to be respected concerning dressings, management of pain
      being marked by an under-utilisation of morphine.

PMID- 20692769
TI  - A randomized, controlled trial of immersive virtual reality analgesia, during
      physical therapy for pediatric burns.
AB  - This randomized, controlled, within-subjects (crossover design) study examined
      the effects of immersive virtual reality as an adjunctive analgesic technique for
      hospitalized pediatric burn inpatients undergoing painful physical therapy. Fifty
      four subjects (6-19 years old) performed range-of-motion exercises under a
      therapist's direction for 1-5 days. During each session, subjects spent
      equivalent time in both the virtual reality and the control conditions (treatment
      order randomized and counterbalanced). Graphic rating scale scores assessing the
      sensory, affective, and cognitive components of pain were obtained for each
      treatment condition. Secondary outcomes assessed subjects' perception of the
      virtual reality experience and maximum range-of-motion. Results showed that on
      study day one, subjects reported significant decreases (27-44%) in pain ratings
      during virtual reality. They also reported improved affect ("fun") during virtual
      reality. The analgesia and affect improvements were maintained with repeated
      virtual reality use over multiple therapy sessions. Maximum range-of-motion was
      not different between treatment conditions, but was significantly greater after
      the second treatment condition (regardless of treatment order). These results
      suggest that immersive virtual reality is an effective nonpharmacologic,
      adjunctive pain reduction technique in the pediatric burn population undergoing
      painful rehabilitation therapy. The magnitude of the analgesic effect is
      clinically meaningful and is maintained with repeated use.

PMID- 20692770
TI  - Acupuncture accelerates wound healing in burn-injured mice.
AB  - The effects of acupuncture on healing of deep second degree burns were compared
      to the conventional hydrocolloid dressing, Duoderm in mice. The expression level
      of inflammatory protein-1alpha (MIP-1alpha) was significantly reduced in the
      injured skin and the number of eosinophils in blood decreased significantly
      following the acupuncture treatment compared to the Duoderm dressing at 7 days
      after the burn. In addition, the acupuncture treatment was more effective in
      decreasing the wound size and inducing epidermal regeneration. Histological
      findings also revealed that there was less leukocyte infiltration and a greater
      reduction in the immunohistochemical reaction to MIP-2 in the wounds treated with
      acupuncture versus Duoderm. Furthermore, the numbers of BrdU- and basic
      fibroblast growth factor (bFGF)-positive cells were significantly increased by
      the acupuncture treatment, compared to the Duoderm treatment at 7 days. Moreover,
      in the acupuncture treated mice, the expression of fibronectin was increased and
      alpha-SMA was decreased at 7 days. Thus, this present study demonstrates that
      acupuncture accelerates the skin regeneration process following deep second
      degree burns.

PMID- 20692772
TI  - [Down syndrome screening: from medical criticism to crisis of conscience].

PMID- 20692771
TI  - Sexual victimization and hazardous drinking among heterosexual and sexual
      minority women.
AB  - AIMS: Although research shows that sexual minority women report high rates of
      lifetime sexual victimization and high rates of hazardous drinking, investigators
      have yet to explore the relationships between sexual victimization and hazardous
      drinking in this population. In addition, because the rates of these problems may
      vary within the sexual minority population, we examined and compared
      relationships between sexual victimization and hazardous drinking in exclusively
      heterosexual and sexual minority (mostly heterosexual, bisexual, mostly lesbian
      and exclusively lesbian) women. METHOD: Data from 548 participants in the
      National Study of Health and Life Experiences of Women and 405 participants in
      the Chicago Health and Life Experiences of Women study were pooled to address
      these relationships. We compared hazardous drinking, childhood sexual abuse
      (CSA), adult sexual assault (ASA), and revictimization (both CSA and ASA) across
      the five sexual identity subgroups. We then fit a multilevel general linear model
      to examine group differences in the relationships between hazardous drinking and
      sexual victimization and to test for potential interactions between victimization
      and identity on hazardous drinking. RESULTS: Sexual minority women reported
      higher levels of hazardous drinking and higher rates of CSA and sexual
      revictimization than did exclusively heterosexual women. Revictimization was the
      strongest predictor of hazardous drinking among women who identified as mostly
      heterosexual and mostly lesbian. CONCLUSIONS: This study extends previous
      research by examining associations between sexual victimization and hazardous
      drinking in heterosexual and sexual minority women and by exploring within-group
      variations in these associations among sexual minority women. Higher rates of
      lifetime sexual victimization and revictimization may help to explain sexual
      minority women's heightened risk for hazardous drinking. The findings highlight
      the need for additional research that examines the meanings of sexual identity
      labels to more fully understand differences in risk within groups of sexual
      minority women as well as how sexual identity may affect responses to and
      interpretations of sexual victimization.

PMID- 20692773
TI  - [Robotic gynecologic surgery: state of the art. Review of the literature].
AB  - Tele-operating robots, that have been developing for 10 years, are a revolution
      in the field of minimally invasive gynaecology. Indeed, by restoring three
      dimensional view and the surgeon's hand freedom, the robot diminishes the
      technical difficulties of laparoscopy. The robot brings the surgeon back to open
      air movements while preserving the minimally invasive aspect of the procedure and
      should, therefore, allow an easier transition for laparotomic surgeons to
      minimally invasive techniques. However, some inconvenients remain: the robot's
      size, its time-consuming installation, the lack of force feedback and the cost of
      robotic surgery. To this day, the robot was used in gynaecology for tubal
      reversal, myomectomies, hysterectomies, promontofixations and the treatment of
      gynaecological cancers, but the benefits compared to laparoscopic techniques have
      not yet been demonstrated and will require large scale prospective studies. These
      benefits will also have to be weighed up to the cost and organizational
      constraints.

PMID- 20692774
TI  - [Role of deambulation during labour: A prospective randomized study].
AB  - OBJECTIVE: To assess the effects of ambulation during the first stage of labor on
      the duration of labor and other maternal and infant outcomes. PATIENTS AND
      METHODS: A prospective randomized trial conducted from 1st November 2008 to 31st
      March 2009 at the department of obstetrics and gynecology, CHU Farhat Hached,
      Sousse, Tunisia. Two hundred mothers with uncomplicated term pregnancies were
      randomly assigned to one of two groups: first group (100 parturients) authorized
      to ambulate until 6cm of cervical dilation and a second group (100 parturients)
      confined to bed in dorsal or lateral recumbence. RESULTS: Upright position
      reduces significantly (for about 34%) the duration of the first stage of labor
      (P<0.0001), the pain intensity, the oxytocin consumption (P=0.001), the rate of
      delivery by cesarean section and of instrumental deliveries. Upright position
      leads also to a net improvement of the maternal outcome (7% side effects versus
      13%) and the fetal outcome (net improvement of the Apgar's score at first and
      fifth minute, and reduction of a factor 5 of the rate of transfer to the
      neonatology clinical care unit. CONCLUSION: Our study allowed to confirm the
      benefits of ambulation on labor progress as well as on the maternal comfort and
      the maternofetal outcome.

PMID- 20692775
TI  - [Contributions of the ex vivo human perfused placenta in the study of placental
      transfer of drugs].
AB  - Perfused human placental lobule was developed during the 1970s. Only this model
      respects the anatomical features of the human placenta. This approach allows
      different technical conditions (concentrations of drugs...) without ethical
      problems. Limitations of this ex vivo model are detailed in this review, also its
      recent contributions in better understanding of placental passage of drugs.

PMID- 20692776
TI  - [Individual factors and mortality associated with hormone replacement therapy in
      a French cohort of women from 60 to 69 years of age].
AB  - OBJECTIVES: Given the specificity of French postmenopausal hormonal replacement
      therapy, we study the link with overall mortality. MATERIALS AND METHODS: A
      cohort of 1200 women from 60 to 69 years of age was followed up from 2001 to
      2009. We computerized from the health care repayment database the current
      reimbursement of behind-the-counter hormonal therapy. We sent a questionnaire to
      identify their lifetime history of hormone use. We test whether current and
      former users have higher risk of death from all cause combined. We adjusted the
      survival analysis on the individuals factors associated to the hormone use. The
      statistical methods Kaplan-Meier curves in univariate analysis and Cox Regression
      Model in multivariate analysis were used. RESULTS: Current users present a
      reduced all-cause mortality rate while former users have a higher all-cause
      mortality rate. This trend suggests a "healthy estrogen user survivor effect"
      bias. After adjustment on confounding factors, hormonal users do not have a
      statistically significant increased risk of overall mortality. CONCLUSION:
      Postmenopausal hormone replacement therapy is not linked with mortality for women
      from 60 to 69 years of age covered by the self-employed workers health and
      retirement French insurance fund.

PMID- 20692777
TI  - [Tetragametic chimerism: Case report].
AB  - We report the third case of spontaneous monochorionic dizygous pregnancy,
      discovered on foetal sex discordance. Blood group testing on the female twin
      revealed a hematopoietic chimera. The mechanism of monochorionic dizygous
      formation could be the fusion of two independent zygotes at a late morula stage.
      A single placental mass with vascular anastomosis then develops. Stem cells
      exchanged during early foetal life can thus lead to chimeras, in similar
      conditions to stem cell transfusion in adults. Immaturity of the foetal immune
      system allows cell graft in the other twin's marrow. Assisted reproductive
      procedures are believed to promote such pregnancies.

PMID- 20692778
TI  - Which indicators can public health authorities use to monitor prescription drug
      abuse and evaluate the impact of regulatory measures? Controlling High Dosage
      Buprenorphine abuse.
AB  - BACKGROUND: Two methods have been recently developed from a drug reimbursement
      database to provide useful indicators for public health authorities concerning
      the abuse potential of psychotropic drugs. The doctor-shopping indicator (DSI)
      measures the proportion of the drug obtained by doctor shopping among the overall
      quantity of the drug reimbursed and the clustering method reveals subgroups of
      deviant patients. OBJECTIVE: The objective of the study was to analyze and
      compare indicators resulting from these two methods, applied to High Dosage
      Buprenorphine (HDB) (a product well-known to be diverted in France), in order to
      determine which public health authorities needs they answer. DATA ANALYSIS: The
      patients with reimbursed HDB were grouped using the clustering method in terms of
      drug dispensations characteristics over a nine month period. The characteristics
      of the resulting subgroups, including their DSI, were then compared. RESULTS:
      4787 Patients (73.4%) had no measurable doctor-shopping behaviour. But the
      comparison of the two methods demonstrated that the more a patient's profile was
      characterized by deviant behavior, the higher was the DSI: from 0.4% in a
      subgroup with a median profile to 72% in a subgroup with a deviant profile.
      CONCLUSION: These two methods are useful surveillance tools for public health
      authorities: the clustering method may help devise pertinent intervention
      strategies to reduce prescription drug abuse while the DSI method provides
      quantitative information demonstrating whether these strategies are useful. We
      discuss the advantages and disadvantages of using these two methods as useful
      indicators for public health authorities.

PMID- 20692779
TI  - Executive and intellectual functions in attention-deficit/hyperactivity disorder
      with and without comorbidity.
AB  - BACKGROUND: Recent neuropsychological theories have targeted deficient executive
      functions (EF) as the main characteristic of Attention Deficit Hyperactivity
      Disorder (ADHD), but the nature of the neuropsychological deficits remains
      elusive and findings are heterogeneous. In particular, it is still unclear
      whether ADHD subtypes and comorbidity affect intellectual and executive
      functioning, because large variability has been found in different patient
      populations. Furthermore, the role of IQ in EF deficits in individuals with ADHD
      has been debated. METHODS: The aim of the present research was to study in detail
      the relationship between EF, ADHD subtypes, and comorbid diagnosis by taking into
      account the potential role of IQ. For this purpose, 23 children (aged from 5 to
      16 years; 20 males and 3 females) with a diagnosis of ADHD were selected.
      RESULTS: Data show no differences between children with different subtypes of
      ADHD on measures of EF, but they evidence differences on EF measures in children
      with different comorbidities (internalizing versus externalizing disorder).
      Namely, compared to the internalizing disorders group, the children with
      externalizing disorders obtained significantly lower scores on different measures
      of EF (i.e., verbal working memory and categorical fluency), but these
      differences were strictly dependent on IQ level. CONCLUSIONS: Comorbidity
      patterns, rather than ADHD subtypes, appear to be more valid for defining the
      neuropsychological features of the ADHD endophenotype. Moreover, general
      intelligence seems to play a substantial role in the cognitive processes
      underling the disorder, especially in relation to externalizing aspects.

PMID- 20692780
TI  - Portal biliopathy.

PMID- 20692781
TI  - Malignant portal vein thrombosis.

PMID- 20692782
TI  - Spin-echo SS-PARSE: a PARSE MRI method to estimate frequency, R(2) and R(2)(') in
      a single shot.
AB  - Spin-echo signals allow separate measurements of irreversible and reversible
      relaxation rates in MRI. A spin-echo version of single-shot parameter assessment
      by retrieval from signal encoding (SE-SS-PARSE) method has been developed to
      quantitatively and accurately map transverse magnetization magnitude, frequency,
      irreversible and reversible relaxation rates in a single shot. These image
      parameters can be applied to fMRI research as well as a number of neuroimaging
      applications. Following a description of the signal model, this article
      demonstrates the performance of SE-SS-PARSE in simulations with different noise
      levels and in phantom experiments. By solving an inverse problem, the estimated
      irreversible and reversible relaxation rates in SE-SS-PARSE are highly correlated
      with the reference relaxation rates from a standard technique (correlation
      coefficients: r(1)=0.9636 for reversible relaxation rate, r(2)=0.9788 for
      irreversible relaxation rate). The rapid SE-SS-PARSE technique has the potential
      to monitor transient changes in R(2) and R(2)(') while minimizing motion
      artifacts and also is free of geometric and ghosting errors. It is expected that
      this fast scan technique will find applications in both scientific research and
      clinical diagnosis.

PMID- 20692783
TI  - Highly undersampled supraaortic MRA at 3.0 T: initial results with parallel
      imaging in two directions using a 16-channel neurovascular coil and parallel
      imaging factors up to 16.
AB  - PURPOSE: To present the feasibility of highly undersampled contrast-enhanced MRA
      (CE-MRA) of the supraaortic arteries with a 16-channel neurovascular coil at 3.0
      T using parallel imaging in two directions with parallel imaging factors (PIF) up
      to 16. MATERIALS AND METHODS: Institutional review board approval and informed
      consent were obtained. In a prospective study, MRA protocols including PIF of 1,
      2, 4, 9 and 16 yielding a spatial resolution from 0.81*0.81*1.0 mm(3) to
      0.46*.46*0.98 mm(3) were acquired. In 32 examinations, image quality and vascular
      segments were rated independently by two radiologists. SNR estimations were
      performed for all MRA protocols. RESULTS: The use of high PIF allowed to shorten
      acquisition time from 2:09 min down to 1:13 min and to increase the anatomic
      coverage while maintaining or even increasing spatial resolution down to
      0.46*0.46*0.98 mm(3). The larger anatomic coverage that was achieved with the use
      of high PIF allowed for visualization of vascular structures that were not
      covered by the standard protocols. Despite the resulting lower SNR using high
      PIF, image quality was constantly rated to be adequate for diagnosis or better in
      all cases. CONCLUSION: The use of high PIF yielded diagnostic image quality and
      allowed to increase the anatomic coverage while maintaining or even improving
      spatial resolution and shortening the acquisition time.

PMID- 20692784
TI  - Three-dimensional T(1), T(2) and proton density mapping with inversion recovery
      balanced SSFP.
AB  - By combining a balanced steady-state free precession (bSSFP) readout with an
      initial inversion pulse, all three contrast parameters, T(1), T(2) and proton
      density (M(0)), may be rapidly calculated from the signal progression in time.
      However, here it is shown that this technique is quite sensitive to variation in
      the applied transmit RF (B(1)) field, leading to pronounced errors in calculated
      values. Two-dimensional (2D) acquisitions are taxed to accurately quantify the
      relaxation, as the short RF pulses required by SSFP's rapid TR contain a broad
      spectrum of excitation angles. A 3D excitation using a large diameter excitation
      coil was able to correctly quantify the parameters. While the extreme B(1)
      sensitivity was previously problematic and has precluded use of IR-bSSFP for
      relaxometry, in this work these obstacles were significantly reduced, allowing
      the rapid quantification of T(1), T(2) and M(0). The results may further be used
      to simulate image contrast from common sequences, such as a T(1)-weighted or
      fluid-attenuated inversion recovery (FLAIR) examination.

PMID- 20692785
TI  - Small bowel perforation secondary to fish bone ingestion managed non-operatively.
AB  - BACKGROUND: The presurgical diagnosis of foreign body (FB)-induced bowel
      perforation is exceedingly difficult. Perforation most commonly occurs in the
      ileocecal region and typically mimics diagnoses more common to the right lower
      quadrant (RLQ), including appendicitis and diverticulitis. OBJECTIVES: This
      report will discuss the events of this particular case of fish bone ingestion and
      subsequent small bowel perforation and the epidemiology, diagnosis, and
      management of FB ingestions. CASE REPORT: This case describes a 28-year-old man
      who presents with a 4-h history of sharp, stabbing abdominal pain localized to
      the RLQ. Abdominal computed tomography revealed a 1.5-cm curvilinear foreign body
      traversing through a loop of small bowel in the RLQ. Upon further questioning,
      the patient recalled eating northern pike 2 days before. During his hospital
      stay, the patient noted improvement of his symptoms and thus was managed non
      operatively without complication. The patient was discharged after complete
      resolution of his abdominal pain on hospital day number 2. CONCLUSION: This
      represents a rare case of small bowel perforation secondary to fish bone
      ingestion that was managed non-operatively without complication.

PMID- 20692786
TI  - Ventilator-associated pneumonia: the potential critical role of emergency
      medicine in prevention.
AB  - BACKGROUND: Delivery of critical care within a certain window of opportunity is
      paramount in many disease states, and providing the right care to these patients
      at the right time in the Emergency Department (ED) can significantly reduce
      mortality. However, aggressive treatment of these patients often requires
      endotracheal intubation and mechanical ventilation either in the pre-hospital or
      ED phase of care. Care of mechanically ventilated patients in the ED is not
      trivial or without potential complications, including ventilator-associated
      pneumonia (VAP). OBJECTIVE/DISCUSSION: This article summarizes the epidemiology,
      pathophysiology, and specific risk factors associated with VAP and provides
      evidence-based recommendations for its prevention. We emphasize practices that
      are particularly important in the early stages of care of intubated, mechanically
      ventilated patients; thus, they should be instituted in the ED. CONCLUSION:
      Specifically, we recommend continuous backrest elevation of 30-45 degrees ,
      chlorhexidine application to the oral cavity after intubation and every 12h
      thereafter, orotracheal intubation with a tube that enables continuous subglottic
      suctioning, and cuff pressure assessments after intubation and every 4h
      thereafter to maintain pressure between 20 and 30cm H(2)O.

PMID- 20692787
TI  - Encapsulating peritoneal sclerosis and aortic calcification with near-total
      occlusion.

PMID- 20692788
TI  - S100b immunoassay: an assessment of diagnostic utility in minor head trauma.
AB  - BACKGROUND: Over 1.4 million patients present annually to United States (US)
      emergency departments with minor head trauma. Many undergo unnecessary head
      computed tomography (HCT). OBJECTIVES: We sought to determine the diagnostic
      accuracy of S100B, a central nervous system peptide, to screen for HCT+ head
      injury. METHODS: This study was a prospective observational study of adults with
      minor head trauma. Patients presenting within 6h of injury and undergoing HCT for
      evaluation were eligible. All HCTs were blindly reviewed for presence of a priori
      defined intracranial injury (HCT+). Quantitative S100B levels were determined by
      enzyme-linked immunosorbent assay. RESULTS: A total of 346 patients were enrolled
      over 12 months, mean age 48 years (+/- 23 years), 62% male. Twenty-two (6.4%)
      were HCT+. Vomiting, headache, anterograde amnesia, Glasgow Coma Scale score<15,
      nausea, and loss of consciousness were associated with HCT+ results. Median S100B
      levels were significantly elevated in HCT+ (115 ng/dL) vs. HCT- (56.0 ng/dL)
      patients (p=0.032). Receiver operator characteristic analysis demonstrated an
      area under the curve of 0.643. Sensitivity and specificity were 86% (95%
      confidence interval [CI] 67-96) and 37% (95% CI 29-45%) at 42 ng/dL, 91% (95% CI
      72-98%) and 24% (95% CI 17-31%) at 32 ng/dL, and 96% (95% CI 78-100%) and 13%
      (95% CI 9-20%) at 24 ng/dL, respectively. CONCLUSION: The study demonstrates that
      S100B may be a sensitive but non-specific marker of HCT+ injury.

PMID- 20692789
TI  - A comparison of the standard bolia technique versus subintimal recanalization
      plus Viabahn stent graft in the management of femoro-popliteal occlusions.
AB  - OBJECTIVE: To assess the potential benefit of the addition of a covered stent to
      a subintimal recanalized artery in patients with femoro-popliteal occlusions.
      METHODS: From September 2003 to October 2005, we retrospectively analyzed all
      patients admitted for severe claudication or critical limb ischemia related to
      long femoro-popliteal occlusions and treated with subintimal recanalization.
      Patients were divided into two groups depending on whether they received a stent
      or not. All patients in the group treated with stent received a stent graft, and
      the entire length of the recanalized artery was covered in each case. Demographic
      data, indications, procedure, and outcomes were examined using survival analysis
      statistical techniques. RESULTS: Fifty-three patients (54 limbs) were treated
      consecutively for severe claudication (n=19) or critical limb ischemia (n=34).
      Thirty-four (64%) had a stent placed, while 19 (35.8%) did not. The mean length
      of the lesions treated was 20.11 cm (range, 5-35 cm). Statistically, there was no
      significant difference in lesion length, Rutherford stage of peripheral-artery
      disease, Transatlantic Inter-Society Consensus classification, and distal run-off
      between the two groups. The technical success rate was 94.5%, and two out of the
      three failures were treated with surgical bypass in one case and major amputation
      in the other. The third patient received only medical treatment. Combined
      procedures were required in the treatment of 68.2% of limbs in the no-stent group
      and 55.8% in the stent group. Mean follow up was 16.9 months (range, 1-35
      months). At 1 year, primary, primary-assisted, and secondary patency for the
      stent vs no-stent groups was, respectively, 61.8% vs 78.9% (P=.49), 70.6% vs
      78.9% (P=.78), and 88.2% vs 78.9% (P=.22). The 1-year limb salvage rate for the
      stent vs no-stent group was 94.1% vs 100% (P=.7). CONCLUSION: Combining
      subintimal angioplasty with a stent graft in femoro-popliteal lesions does not
      improve patency. The limb salvage rate remains high after addition of a stent
      graft. Rigorous monitoring is recommended to diagnose and treat restenosis early
      in order to improve patency.

PMID- 20692791
TI  - Bioengineered vascular graft grown in the mouse peritoneal cavity.
AB  - BACKGROUND: We tested the hypothesis that the mouse peritoneum can function like
      a bioreactor to generate directed bio-engineered tissues such as those used for
      bypass grafting. Additionally, we reasoned that the mouse animal model would
      allow us to elucidate the underlying cellular and molecular mechanisms that are
      responsible for the generation of tissue in peritoneal cavity. METHODS: Plastic
      tubes (two tubes/mouse) were implanted into the peritoneal cavity of three
      strains of mice (C57BL/6, BALB/c, and MRL). The tubes were harvested, tissue
      capsule surrounding the tubes was removed, and analyzed by immunostaining (five
      capsules/five mice/strain) and microarray (three capsules/three mice/strain). In
      addition, the tissue capsules that were harvested from MRL mice (n = 21) were
      grafted into abdominal aorta of the same mice as autografts. The patency of all
      grafts was monitored by micro-ultrasound, and their functionality was assessed by
      laser Doppler imaging of blood flow in femoral arteries. Venous (n = 13) and
      arterial isografts (n = 11) were used as positive controls. In a negative control
      group (five mice/strain), the abdominal aorta was occluded by double ligation
      with 9-0 silk. RESULTS: The implanted plastic tubes required at least 8 weeks of
      incubation in the peritoneum of the three strains of mice in order to generate
      useful grafts. No vascular cells were found in the tissue capsules. Microarray
      analysis of tissue capsules revealed that the capsular cells express a gene
      expression program that is vastly shared among the three strains of mice, and the
      cells exhibit a high degree of plasticity. The micro-ultrasound analysis of the
      grafts showed that 62% of autografts remained patent compared with 77% of venous
      isografts and 91% of arterial isografts. The laser Doppler imaging analysis
      showed that blood flow dropped by 40% and 35% in the autografts and vein
      isografts, respectively, 1 day after surgery. The flow, however, rebounded to the
      level of arterial isografts 1 month post-surgery and remained unchanged among all
      grafts for the next 4 months. Immunostaining of the autografts showed a thick
      vessel wall with endothelial cells that lined the lumen and smooth muscle cells
      that constituted the graft wall. CONCLUSION: The mouse peritoneal cavity of mice
      has the ability to function like a bioreactor to generate bio-engineered tissues.
      The tissue capsules harvested from peritoneal cavity of a mouse are composed of
      nonvascular cells that display phenotype of progenitor cells. After grafting,
      however, the capsule autografts become arterialized and remained patent for at
      least 4 months after surgery, similar to venous or arterial isografts.

PMID- 20692790
TI  - Gender differences in daily ambulatory activity patterns in patients with
      intermittent claudication.
AB  - OBJECTIVES: To compare the pattern of daily ambulatory activity in men and women
      with intermittent claudication, and to determine whether calf muscle hemoglobin
      oxygen saturation (StO2) is associated with daily ambulatory activity. METHODS:
      Forty men and 41 women with peripheral arterial disease limited by intermittent
      claudication were assessed on their community-based ambulatory activity patterns
      for 1 week with an ankle-mounted step activity monitor and on calf muscle StO2
      during a treadmill test. RESULTS: Women had lower adjusted daily maximal cadence
      (mean+/-SE) for 5 continuous minutes of ambulation (26.2+/-1.2 strides/min vs
      31.0+/-1.2 strides/min; P=.009), for 1 minute of ambulation (43.1+/-0.9
      strides/min vs 47.2+/-0.9 strides/min; P=.004), and for intermittent ambulation
      determined by the peak activity index (26.3+/-1.2 strides/min vs 31.0+/-1.2
      strides/min; P=.009). Women also had lower adjusted time to minimum calf muscle
      StO2 during exercise (P=.048), which was positively associated with maximal
      cadence for 5 continuous minutes (r=0.51; P<.01), maximal cadence for 1 minute
      (r=0.42; P<.05), and peak activity index (r=0.44; P<.05). These associations were
      not significant in men. CONCLUSION: Women with intermittent claudication ambulate
      slower in the community setting than men, particularly for short continuous
      durations of up to 5 minutes and during intermittent ambulation at peak cadences.
      Furthermore, the daily ambulatory cadences of women are correlated with their
      calf muscle StO2 during exercise, as women who walk slower in the community
      setting reach their minimum calf muscle StO2 sooner than those who walk at faster
      paces. Women with intermittent claudication should be encouraged to not only walk
      more on a daily basis, but to do so at a pace that is faster than their preferred
      speed.

PMID- 20692792
TI  - Spontaneous retroperitoneal hematoma associated with iliac vein rupture.
AB  - OBJECTIVE: Spontaneous retroperitoneal hematoma (SRH) associated with iliac vein
      rupture is a rare but life-threatening emergency with high operative mortality.
      This study summarizes our experience in providing diagnostic and therapeutic
      management for this rare clinical entity. METHODS: Between May 2002 and May 2009,
      nine patients were admitted to our hospital for SRH and acute deep venous
      thrombosis (DVT). Medical data for demographics, clinical presentation, auxiliary
      examinations, treatment modalities, outcomes, and follow-up were retrospectively
      analyzed. RESULTS: Nine patients (8 women, 1 man) were enrolled in this study.
      All were aged>45 years (range, 46-70 years). The common clinical manifestations
      were sudden onset of left lower abdominal or lumbar pain, swelling of the left
      lower extremity, anemia, and hypotension. Most patients were diagnosed by duplex
      ultrasound imaging and computed tomography scan. Three patients were treated
      conservatively, and six underwent surgical or combined treatments, comprising 2
      repairs of iliac vein, 1 iliac vein ligation and Palma-Dale bypass graft, 1
      pelvic vein ligation, 1 removal of hematoma, and 1 repair of iliac vein,
      thrombectomy, and endovascular stent placement. The iliac vein ruptured in five
      patients. May-Thurner syndrome was found in three patients. One patient died
      after surgery (operative mortality, 16.7%). Postoperative morbidity was 50%. Mean
      volume of perioperative blood transfusion was 900+/-640 mL (range, 0-2000 mL).
      Mean lengths of stay were 2.7+/-1.4 days (range, 2-5 days) in the intensive care
      unit and 16.9+/-2.4 days (range, 14-21 days) in the hospital. Eight patients were
      postoperatively treated with 6 months of warfarin. Mean follow-up was 30.5+/-15.0
      months (range, 6-50 months). The occurrence rate of chronic venous insufficiency
      was 87.5% during follow-up. CONCLUSIONS: SRH with concomitant DVT, especially in
      women aged >45, should be considered in patients with sudden lower abdominal or
      lumbar pain, leg swelling, anemia, and shock. Spontaneous iliac vein rupture and
      the presence of May-Thurner syndrome should be considered in these patients.
      Surgical interventions were associated with high mortality and morbidity. In our
      experience, conservative therapy was safer than open surgical procedures.

PMID- 20692793
TI  - The Semmes Weinstein monofilament examination is a significant predictor of the
      risk of foot ulceration and amputation in patients with diabetes mellitus.
AB  - OBJECTIVE: Diabetic peripheral neuropathy is a major complication of diabetes
      mellitus (DM) and is the leading cause of foot ulceration and lower extremity
      amputations (LEAs). The purpose of this systematic review is to evaluate current
      evidence regarding the prognostic value of the Semmes Weinstein monofilament
      examination (SWME) in predicting foot ulceration and LEA in patients with DM.
      METHODS: The MEDLINE/PubMed database was searched through November 2009 for
      articles pertaining to diabetic foot and SWME with no language or publication
      date restrictions. Prognostic studies with original data assessing the predictive
      value of SWME for foot ulceration or LEA in patients with DM were included in the
      selection. Data were systematically extracted and analyzed by two independent
      investigators. Absolute risks and relative risks were determined for each study.
      RESULTS: Of the 863 studies identified, nine articles were relevant, involving
      11,007 patients with DM. Six studies were identified that assessed the prognostic
      value of SWME regarding diabetic foot ulceration. The relative risk for patients
      with a positive SWME result versus those with a negative result ranged from 2.5
      (95% confidence interval [CI], 2.0 to 3.2) to 7.9 (95% CI, 4.4 to 14.3) in the
      identified studies with follow up between 1 and 4 years. Three of the studies
      assessed the risk of LEA with a positive SWME result. The relative risk for LEA
      ranged from 1.7 (95% CI, 1.1 to 2.6) to 15.1 (95% CI, 4.3 to 52.6) with follow-up
      between 1.5 and 3.3 years. CONCLUSIONS: All nine studies found SWME to be a
      significant and independent predictor of future foot ulceration or likely of
      future LEA as well in patients with DM. Therefore, SWME is an important evidence
      based tool for predicting the prognosis of patients with diabetic foot, thus
      enabling improved patient selection for early intervention and management. More
      research should be conducted to elucidate the relationship between SWME and LEA.

PMID- 20692794
TI  - Carotid artery stenting outcomes are equivalent to carotid endarterectomy
      outcomes for patients with post-carotid endarterectomy stenosis.
AB  - BACKGROUND: Carotid artery stenting (CAS) has been advocated as an alternative to
      redo surgery for patients with post-carotid endarterectomy (CEA) stenosis. This
      study compares early and late clinical outcomes for both groups. METHODS: This
      study analyzes 192 patients: 72 had reoperation (Group A) and 120 had CAS for
      post-CEA stenosis (Group B). Patients were followed prospectively and had duplex
      ultrasounds at 1 month, and every 6 to 12 months thereafter. The perioperative
      complications (perioperative stroke, myocardial infarction/death, cranial nerve
      injury) and 4-year end points were analyzed. A Kaplan-Meier lifetable analysis
      was used to estimate rates of freedom from stroke, stroke-free survival, >=50%
      restenosis, and >=80% restenosis. RESULTS: Demographic/clinical characteristics
      were comparable for both groups, except for diabetes mellitus and coronary artery
      disease, which were significantly higher in Group B. The indications for
      reoperations were transient ischemic attacks/stroke in 72% for Group A versus 57%
      for Group B (P=.0328). The mean follow-up was 33 months (range, 1-86 months) for
      Group A and 24 months (range, 1-78 months) for Group B (P=.0026). The proportion
      of early (<24 months) carotid restenosis prior to intervention was 51% in Group A
      versus 27% in Group B (P=.0013). The perioperative stroke rates were 3% and 1%,
      respectively (P=.5573). There were no myocardial infarctions or deaths in either
      group. The overall incidence of cranial nerve injury was 14% for Group A versus
      0% for Group B (P<.0001). However, there was no statistical difference between
      the groups relating to permanent cranial nerve injury (1% versus 0%). The
      combined early and late stroke rates for Groups A and B were 3% and 2%,
      respectively (P=.6347). The stroke-free rates at 1, 2, 3, and 4 years for Groups
      A and B were 97%, 97%, 97%, and 97% and 98%, 98%, 98%, and 98%, respectively
      (P=.6490). The stroke-free survival rates were not significantly different. The
      rates of freedom from >=50% restenosis at 1, 2, 3, and 4 years were 98%, 95%,
      95%, and 95% for Group A versus 95%, 89%, 80%, and 72% for Group B (P=.0175). The
      freedom from >=80% restenosis at 1, 2, 3, and 4 years for Groups A and B were
      98%, 97%, 97%, and 97% versus 99%, 96%, 92%, and 87%, respectively (P=.2281).
      Four patients (one symptomatic) in Group B had reintervention for >=80%
      restenosis. The rate of freedom from reintervention for Groups A and B were 100%,
      100%, 100%, and 100% versus 94%, 89%, 83%, and 79%, respectively (P=.0634).
      CONCLUSIONS: CAS is as safe as redo CEA. Redo CEA has a higher incidence of
      transient cranial nerve injury; however, CAS has a higher incidence of >=50% in
      stent restenosis.

PMID- 20692795
TI  - Ellagic acid inhibits oxidized LDL-mediated LOX-1 expression, ROS generation, and
      inflammation in human endothelial cells.
AB  - BACKGROUND: LOX-1, a lectin-like receptor on endothelial cells, facilitates the
      uptake of oxidized low-density lipoprotein (oxLDL). Expression of LOX-1 is
      involved in the pathobiological effects of oxLDL in endothelial cells, including
      reactive oxygen species (ROS) generation, suppression of endothelial nitric oxide
      synthase (eNOS) activity, and leukocytic adhesion. Moderate consumption of
      phenolic-enriched food may have a protective effect against the development of
      atherosclerosis via the antioxidant capacity of phenolic compounds at the
      endothelial level. In this study, we determined whether ellagic acid, a
      polyphenolic compound widely distributed in fruits and nuts, protects against
      oxLDL-induced endothelial dysfunction by modulating the LOX-1-mediated signaling
      pathway. METHODS: Human umbilical vein endothelial cells (HUVECs) were pretreated
      with ellagic acid at doses of 5, 10, 15, and 20 MUM for 2 hours and then
      incubated with oxLDL (150 MUg/mL) for an additional 24 hours. RESULTS: LOX-1
      protein expression was markedly lower after exposure to oxLDL in HUVECs
      pretreated with ellagic acid or diphenyleneiodonium, a well-known inhibitor of
      nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, than in HUVECs
      exposed to oxLDL alone, suggesting that ellagic acid deactivates NADPH oxidase.
      We also found that oxLDL activated the membrane assembly of p47phox, Rac1, gp91
      and p22phox, and the subsequent induction of ROS generation; however, ROS
      generation was markedly suppressed in cells pretreated with ellagic acid or anti
      LOX-1 monoclonal antibody. In addition, oxLDL down-regulated eNOS and up
      regulated inducible NO synthase (iNOS), thereby augmenting the formation of NO
      and protein nitrosylation. Furthermore, oxLDL induced the phosphorylation of p38
      mitogen-activated protein kinase, activated the NF-kappaB-mediated inflammatory
      signaling molecules interleukin-(IL) 6 and IL-8 and the adhesion molecules
      intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E
      selectin, and stimulated the adherence of THP-1 (a human acute monocytic leukemia
      cell line) to HUVECs. Pretreatment with ellagic acid, however, exerted
      significant cytoprotective effects in all events. CONCLUSION: Findings from this
      study may provide insight into a possible molecular mechanism by which ellagic
      acid inhibits LOX-1-induced endothelial dysfunction. Our data indicate that
      ellagic acid exerts its protective effects by inhibiting NADPH oxidase-induced
      overproduction of superoxide, suppressing the release of NO by down-regulating
      iNOS, enhancing cellular antioxidant defenses, and attenuating oxLDL-induced LOX
      1 up-regulation and eNOS down-regulation.

PMID- 20692796
TI  - Identifying the source of superficial reflux in venous leg ulcers using duplex
      ultrasound.
AB  - OBJECTIVE: Mapping of venous reflux routes associated with medially or laterally
      located venous leg ulcers and their source of origin. METHODS: This prospective
      report presents the results of duplex investigations performed in consecutive leg
      ulcer patients, all with venous reflux, in a time period over 2 years. A total of
      169 patients (183 legs), with chronic venous leg ulcers (CEAP: C6) were examined
      in a private practice. The data collection integrated an examination that
      included medical history and clinical diagnoses and incorporated measurements
      such as body mass index, oscillometric index, and range of motion of the ankle
      joint. Venous function was assessed with duplex ultrasound, and the cases were
      described using the advanced CEAP classification. Additionally, a "sourcing"
      technique was performed with duplex ultrasound investigation of the ulcer bed and
      the venous system under manual compression and release of the ulcer. The
      principle of "sourcing" is to follow venous reflux from the ulcer area to its
      proximal origin. The detected reflux routes were classified either as "axial" or
      "crossover" type. RESULTS: A total of 20% of the ulcer patients showed no
      clinically visible varicose veins. One hundred three patients had medial ulcers,
      54 lateral ulcers, 21 medial and lateral, and five had gaiter ulcers. Sixty-four
      (35%) of the medially located ulcers had reflux in the great saphenous vein
      (GSV), 28 (15%) showed reflux in the medial perforating veins (axial types), and
      11 (6%) had reflux in the small saphenous vein (SSV; crossover type). From 54
      patients presenting with lateral ulcers, 25 (14%) showed GSV incompetence
      (crossover type) and only 13 (7%) SSV incompetence (axial type). Sixteen patients
      showed refluxes penetrating from deep into lateral perforating veins. CONCLUSION:
      Crossover reflux routes were detected in 25 of 54 (46%) legs with lateral and in
      11 of 103 (11%) legs with medial ulceration (chi2 44.34; P<.001). In venous ulcer
      patients, an extended examination (CEAP classification) and a special duplex
      technique ("sourcing") are recommended to identify the specific route responsible
      for the venous reflux. This seems essential for planning a rational treatment of
      venous reflux ulcers.

PMID- 20692797
TI  - Optimizing supervised exercise therapy for patients with intermittent
      claudication.
AB  - BACKGROUND: The first-line intervention for intermittent claudication is usually
      supervised exercise therapy (SET). The literature describes a range of exercise
      programs varying in setting, duration, and content. The purpose of the present
      study was to examine the exercise protocols offered and to identify the impact of
      the intensity of the SET programs (in terms of frequency, duration, and type of
      exercise) on improvements in walking distance (response) in the first 3 months.
      The present study is part of the Exercise Therapy in Peripheral Arterial Disease
      (EXITPAD) study, a multicenter randomized clinical trial comparing the effects of
      SET provided by regional physiotherapists, with or without daily feedback, on the
      level of activities with the effects of walking advice. METHODS: The analysis
      included patients randomized to receive SET with or without feedback. The
      physical therapists administering the SET were asked to fill out therapy
      evaluation sheets stating frequency, duration, and type of exercises. The
      relationship between training volume and the impact on walking distance was
      explored by dividing training volume data into tertiles and relating them to the
      median change in maximum walking distance at 3 and 12 months. RESULTS: Data of
      169 patients were included in the analysis. A SET program consisting of at least
      two training sessions per week each lasting over 30 minutes, during the first 3
      months of a 1-year program tailored to individual patients' needs led to better
      results in terms of walking distance after 3 and 12 months than the other
      variants. The results of our analysis dividing training volume into tertiles
      suggest that there is a relationship between training volume and improvement in
      walking distance and that at least 590 minutes of training should be offered in
      the first 3 months. No differences were found between program involving only
      walking and a combination of exercises, nor between individual and group
      training. CONCLUSION: A SET programs consisting of at least two training sessions
      a week, each lasting over 30 minutes, should be offered during the first 3 months
      of the SET program to optimize improvement in terms of maximum walking distance.

PMID- 20692798
TI  - Learning new procedures remains one of the most interesting aspects in modern
      practice of medicine, and this series of articles details technical
      considerations common to TEVAR for all indications. Introduction.

PMID- 20692799
TI  - [Obesity: A not well-known digestive precancerous state].

PMID- 20692800
TI  - [Autoimmune blistering skin diseases: recent advances].

PMID- 20692801
TI  - [Cytomegalovirus primary infection with polyradiculoneuritis and myopericarditis
      in a patient without known immunodeficiency].

PMID- 20692802
TI  - [Pemphigoid gestationis].
AB  - Pemphigoid gestationis (PG) is a rare autoimmune bullous dermatosis associated
      with pregnancy. Its previous designation, herpes gestationis, is obsolete. PG is
      characterized by a subepidermic separation induced by the presence of peripheral
      blood autoantibodies against two hemidesmosomal antigens: BPAG1 and BPAG2.
      Clinical diagnosis is confirmed by histology and positive cutaneous
      immunofluorescence tests. The most discriminant examination for other pruritic
      dermatoses of pregnancy is the enzyme-linked immunosorbent assay (Elisa) NC16A BP
      180. First-line treatment is local corticosteroid therapy; if local treatment
      fails, general corticosteroid therapy should be administered. The prognosis is
      good for mother and child, except that there is a risk of preterm delivery and of
      moderate fetal growth restriction. Management in a specialized setting is
      therefore necessary. Recurrence is possible during subsequent pregnancies.

PMID- 20692803
TI  - [Cement-induced finger necrosis].

PMID- 20692805
TI  - Surgical difficulties encountered with use of modular endoprosthesis for limb
      preserving salvage of failed allograft reconstruction after malignant tumor
      resection.
AB  - We reviewed outcomes and discussed surgical difficulties encountered in 10
      patients who had modular endoprosthesis for limb preserving salvage of failed
      allograft reconstruction after malignant tumor resection. Mean allograft survival
      time before failure was 127.4 months (range, 14-264 months). Mean length of
      follow-up since endoprosthesis revision surgery was 62.8 months (range, 16-132
      months). There was one endoprosthesis failure, resulting in a mean endoprosthesis
      survival time of 56.9 months (range, 16-132). Complications included arterial
      laceration, nerve injury, periprosthetic crack fracture, aseptic loosening, and
      infection. Modular endoprosthesis remain a viable option that should be
      considered in any limb preserving salvage of failed allograft reconstructions.
      However, altered anatomy, poor/short remnant host bone, periprosthetic fractures,
      inadequate soft tissue coverage and infection remain important difficulties
      encountered.

PMID- 20692806
TI  - The psychometric qualities of four observational pain tools (OPTs) for the
      assessment of pain in elderly people with osteoarthritic pain.
AB  - CONTEXT: Pain in cognitively impaired elderly people (CIEP) often goes
      unrecognized. Observational pain tools (OPTs) have been designed, but with
      limited evidence to support their psychometric qualities. OBJECTIVES: This study
      compared four OPTs (the Pain Assessment IN Advanced Dementia [PAINAD], Abbey Pain
      Scale [Abbey PS], Pain Assessment Checklist for Seniors with Limited Ability to
      Communicate [PACSLAC], and Discomfort Scale--Dementia of Alzheimer Type [DS
      DAT]), two self-report scales, and two proxy-report scales in assessing
      osteoarthritic (OA) pain among CIEP. METHODS: Participants (n=124) were divided
      into two groups: cognitively intact and impaired. They were observed by two
      raters simultaneously at rest and during a standardized exercise program. Besides
      reliabilities, the correlation between the OPTs and the self-report/proxy-report
      scores was evaluated. The OPT scores collected during different activity levels
      were compared to establish the convergent and discriminant validity. Confirmatory
      factor analysis was used to evaluate the construct validity. RESULTS: Similar and
      accepted patterns of reliability/validity were obtained for all OPTs, in which
      better levels of psychometric properties were consistently obtained during
      exercise. However, a single construct (OA pain) appeared only in the PAINAD and
      Abbey PS after deletion of the "breathing" and "physiological change" indicators,
      respectively. This showed that OPTs were better used to detect OA pain when pain
      was triggered by movement (i.e., an exercise program). CONCLUSION: The PAINAD and
      Abbey PS appeared to be more reliable and valid for assessing OA pain while using
      an exercise program among elderly people, regardless of their cognitive ability.

PMID- 20692807
TI  - Nursing staff, patient, and environmental factors associated with accurate pain
      assessment.
AB  - CONTEXT: Although pain ranks highly among reasons for seeking care, routine pain
      assessment is often inaccurate. OBJECTIVES: This study evaluated factors
      associated with nurses (e.g., registered) and other nursing support staff (e.g.,
      licensed vocational nurses and health technicians) discordance with patients in
      estimates of pain in a health system where routine pain screening using a 0-10
      numeric rating scale (NRS) is mandated. METHODS: This was a cross-sectional,
      visit-based, cohort study that included surveys of clinic outpatients (n=465) and
      nursing staff (n=94) who screened for pain as part of routine vital sign
      measurement during intake. These data were supplemented by chart review. We
      compared patient pain levels documented by the nursing staff (N-NRS) with those
      reported by the patient during the study survey (S-NRS). RESULTS: Pain
      underestimation (N-NRS<S-NRS) occurred in 25% and overestimation (N-NRS>S-NRS) in
      7% of the cases. Nursing staff used informal pain-screening techniques that did
      not follow established NRS protocols in half of the encounters. Pain
      underestimation was positively associated with more years of nursing staff work
      experience and patient anxiety or post-traumatic stress disorder and negatively
      associated with better patient-reported health status. Pain overestimation was
      positively associated with nursing staff's use of the full NRS protocol and with
      a distracting environment in which patient vitals were taken. CONCLUSION: Despite
      a long-standing mandate, pain-screening implementation falls short, and informal
      screening is common.

PMID- 20692808
TI  - Social skills: differences among adults with intellectual disabilities, co-morbid
      autism spectrum disorders and epilepsy.
AB  - Assessing social skills is one of the most complex and challenging areas to study
      because behavioral repertoires vary depending on an individual's culture and
      context. However, researchers have conclusively demonstrated that individuals
      with intellectual disabilities (ID) have impaired social skills as well as those
      with co-morbid autism spectrum disorders (ASD) and epilepsy. However, it is
      unknown how these groups differ. Assessment of social skills was made with the
      Matson Evaluation of Social Skills for Individuals with Severe Retardation. One
      hundred participants with ID were matched and compared across four equal groups
      comprising 25 participants with ID, 25 participants with epilepsy, 25
      participants with ASD, and 25 participants with combined ASD and epilepsy. When
      controlling for age, gender, race, level of ID, and hearing and visual
      impairments, significant differences were found among the four groups on the
      MESSIER, Wilks's Lambda=.58, F(18, 257)=3.05, p<.01. The multivariate eta(2)
      based on Wilks's Lambda was .17. Significant differences were found on the
      Positive Verbal subscale, F(3, 96)=3.70, p<.01, eta(2)=.10, Positive Non-verbal
      subscale, F(3, 96)=8.95, p<.01, eta(2)=.22, General Positive subscale, F(3,
      96)=7.30, p<.01, eta(2)=.19, Negative Non-verbal subscale, F(3, 96)=5.30, p<.01,
      eta(2)=.14, and General Negative subscale, F(3, 96)=3.16, p<.05, eta(2)=.09.
      Based on these results, individuals with ID expressing combined co-morbid ASD and
      epilepsy had significantly more impaired social skills than the ID only or groups
      containing only a single co-morbid factor with ID (ASD or epilepsy only).
      Implications of these findings are discussed.

PMID- 20692809
TI  - The use of clozapine among individuals with intellectual disability: a review.
AB  - Clozapine has been approved in the United States since 1990 for refractory or
      treatment resistant schizophrenia in the general population. However, as with
      many other antipsychotic medications, it is being prescribed for reasons other
      than those indicated. Among individuals with intellectual disabilities, clozapine
      is increasingly being prescribed to treat behavioral problems, although the
      empirical evidence for such a practice is lacking. This review was undertaken as
      an attempt to summarize the available studies regarding the use of clozapine for
      behavioral purposes among individuals with intellectual disabilities. Findings of
      our review suggest that the effectiveness of clozapine in targeting challenging
      behaviors among individuals with intellectual disabilities is relatively
      inconclusive at present. We discuss reasons why these limitations exist and offer
      some solutions to help alleviate these limitations.

PMID- 20692810
TI  - Reducing and eliminating restraint of people with developmental disabilities and
      severe behavior disorders: an overview of recent research.
AB  - This paper provides a brief overview of the most recent research (1999-2009) on
      restraint reduction and elimination efforts in the literature and also examines
      the characteristics of restraint along with the risks and benefits. Some earlier
      papers were included in this review because of their importance to the topic. The
      results of this literature review are discussed in terms of implications for
      practitioners and researchers.

PMID- 20692811
TI  - Serum levels of lamotrigine during delivery in mothers and their infants.
AB  - PURPOSE: We followed up lamotrigine transport through the placenta and analyzed
      maternal and umibilical cord concentrations, its ratio and maternal lamotrigine
      clearance in monotherapy and in combinations. METHODS: Maternal and umbilical
      cord concentrations were analyzed during delivery in a cohort of 63 women between
      2001 and 2009. The request forms for routine therapeutic drug monitoring were
      used as the data source. Maternal concentrations were used for the estimation of
      apparent oral clearance and paired infant and maternal concentrations for
      estimation of the infant (umibilical cord)/maternal serum concentration ratio.
      RESULTS: The lamotrigine infant/maternal serum concentration ratio ranged in
      monotherapy from 0.40 to 1.38 (median 0.91). The ratio in monotherapy showed a
      possible distribution to two subgroups. Concomitant administration of valproic
      acid significantly increased both maternal and infant lamotrigine concentrations
      and significantly decreased lamotrigine clearance by about 65%. Co-medication
      with carbamazepine increased lamotrigine clearance non-significantly. Highly
      significant correlations were found between maternal and umbilical cord
      lamotrigine concentrations, both in monotherapy and in the lamotrigine+valproic
      acid combination. Infant concentrations of valproic acid were found to be about
      30% higher and infant concentrations of carbamazepine were found to be about 20%
      lower than maternal concentrations. CONCLUSIONS: Our data from the large cohort
      showed the interindividual variability of umbilical cord/maternal serum
      concentration ratio in lamotrigine monotherapy caused probably by the different
      activity of the placental lamotrigine metabolizing enzymes UGT1A4 and 2B7
      associated with genetic polymorphism. The potential teratogenic effect of
      lamotrigine combination with valproic acid could be associated with the higher
      lamotrigine and valproic acid concentrations in the fetus.

PMID- 20692812
TI  - Third degree heart block following intramuscular ziprasidone.

PMID- 20692813
TI  - Gene-wide association study between the methylenetetrahydrofolate reductase gene
      (MTHFR) and schizophrenia in the Japanese population, with an updated meta
      analysis on currently available data.
AB  - Methylenetetrahydrofolate reductase (MTHFR) is a critical molecule for single
      carbon transfer reactions. Recent evidence suggests that polymorphisms of MTHFR
      are related to neural tube deficits and the pathogenesis of schizophrenia. While
      several studies have demonstrated associations between the gene encoding the
      MTHFR (MTHFR) polymorphisms and schizophrenia, these studies lack consistency.
      Therefore, we conducted a gene-wide association study (patients with
      schizophrenia = 696, control subjects = 747) and performed imputation analysis.
      Additionally, we performed meta-analysis on currently available data from 18
      studies for two common functional polymorphisms (rs1801131 and rs1801133). There
      were no significant associations with schizophrenia in the single marker analysis
      for the seven tagging SNPs of MTHFR. In the haplotypic analysis, a nominally
      significant association was observed between the haplotypes, which included four
      SNPs (rs1801133, rs17421511, rs17037396, and rs9651118) and the schizophrenic
      patients. Additionally, the imputation analysis demonstrated there were several
      associated markers on the MTHFR chromosomal region. However, confirmatory
      analyses of three tagging SNPs (rs1801133, rs17037396, and rs9651118) and the top
      SNP (rs17421511) for the imputation results (patients with schizophrenia = 797,
      control subjects = 1025) failed to replicate the haplotypic analysis and the
      imputation results. These findings suggest that MTHFR polymorphisms are unlikely
      to be related to the development of schizophrenia in the Japanese population.
      However, since our meta-analysis results demonstrated strong support for
      association of rs1801133 with schizophrenia, further replication studies based on
      a gene-wide approach need to be considered.

PMID- 20692814
TI  - Head-to-head comparisons of metabolic side effects of second generation
      antipsychotics in the treatment of schizophrenia: a systematic review and meta
      analysis.
AB  - OBJECTIVE: The metabolic side effects of second-generation antipsychotics (SGA)
      are serious and have not been compared head to head in a meta-analysis. We
      conducted a meta-analysis of studies comparing the metabolic side effects of the
      following SGAs head-to-head: amisulpride, aripiprazole, clozapine, olanzapine,
      quetiapine, risperidone, sertindole, ziprasidone, zotepine. METHOD: We searched
      the register of the Cochrane schizophrenia group (last search May 2007),
      supplemented by MEDLINE and EMBASE (last search January 2009) for randomized,
      blinded studies comparing the above mentioned SGA in the treatment of
      schizophrenia or related disorders. At least three reviewers extracted the data
      independently. The primary outcome was weight change. We also assessed changes of
      cholesterol and glucose. The results were combined in a meta-analysis. RESULTS:
      We included 48 studies with 105 relevant arms. Olanzapine produced more weight
      gain than all other second-generation antipsychotics except for clozapine where
      no difference was found. Clozapine produced more weight gain than risperidone,
      risperidone more than amisulpride, and sertindole more than risperidone.
      Olanzapine produced more cholesterol increase than aripiprazole, risperidone and
      ziprasidone. (No differences with amisulpride, clozapine and quetiapine were
      found). Quetiapine produced more cholesterol increase than risperidone and
      ziprasidone. Olanzapine produced more increase in glucose than amisulpride,
      aripiprazole, quetiapine, risperidone and ziprasidone; no difference was found
      with clozapine. CONCLUSIONS: Some SGAs lead to substantially more metabolic side
      effects than other SGAs. When choosing an SGA for an individual patient these
      side effects with their potential cause of secondary diseases must be weighed
      against efficacy and characteristics of the individual patient.

PMID- 20692815
TI  - Diagnostic profile and suicide risk in schizophrenia spectrum disorder.
AB  - BACKGROUND: Earlier studies of patients with schizophrenia have investigated
      suicide risk in relation to specific psychiatric symptoms, but it remains to be
      better understood how suicide risk relates to the diagnostic profile in these
      patients. METHODS: We identified all patients with a first clinical ICD-diagnosis
      of schizophrenia, schizophreniform or schizoaffective disorder in Stockholm
      County between 1984 and 2000. Patients who died by suicide within five years from
      diagnosis were defined as cases (n=84) and were individually matched with a
      similar number of living controls from the same population. Sociodemographic and
      clinical variables were retrieved from hospital records through a blind process.
      DSM-IV lifetime diagnoses for cases and controls were derived using the OPCRIT
      algorithm. RESULTS: A schizophrenia spectrum diagnosis (i.e. schizophrenia,
      schizophreniform or schizoaffective disorder) was assigned by OPCRIT to 50% of
      the suicide cases and 62% of the controls. Criteria for schizophrenia were met by
      41% of the cases and 51% of the controls; for schizoaffective disorder by 8% of
      the cases and 10% of the controls; for other psychosis by 23% of the cases and
      25% of the controls; and for mood disorder by 26% of the cases and 12% of the
      controls. Using the schizophrenia diagnosis as a reference, suicide risk was
      significantly higher in patients meeting criteria for a mood disorder diagnosis
      with an adjusted odds ratio of 3.3 (95% CI 1.2-9.0). CONCLUSION: In patients with
      a clinical schizophrenia spectrum diagnosis, a DSM-IV mood disorder diagnosis
      increases the suicide risk more than three-fold.

PMID- 20692816
TI  - Isolation of meticillin-resistant Staphylococcus aureus (MRSA) from swine in
      Japan.
AB  - Meticillin-resistant Staphylococcus aureus (MRSA) sequence type (ST) 398 is
      widely prevalent in swine in Europe and North America. To determine the
      prevalence of MRSA, and specifically ST398, in Japanese swine, a total of 115
      nasal swabs and 115 faecal samples from swine reared at 23 farms located in
      eastern Japan were investigated. MRSA was isolated from a nasal sample (0.9%) but
      not from any faecal samples. The strain of MRSA was classified as ST221 by
      multilocus sequence typing and as t002 by spa typing. The MRSA isolate exhibited
      resistance to ampicillin, meticillin and dihydrostreptomycin. Interestingly, it
      remained susceptible to cefazolin, ceftiofur, imipenem, gentamicin, kanamycin,
      chloramphenicol, oxytetracycline, erythromycin, azithromycin, tylosin,
      vancomycin, enrofloxacin and trimethoprim. The prevalence of MRSA amongst swine
      was low and MRSA ST398 was not recovered in the present study.

PMID- 20692817
TI  - Optimized immobilization of gold nanoparticles on planar surfaces through
      alkyldithiols and their use to build 3D biosensors.
AB  - This paper describes a controlled way to immobilize gold nanoparticles on planar
      gold surfaces and the use of the resulting 3D platform to build up a 3D
      biosensor. The surface was first functionalized by grafting hexanedithiol, this
      molecule has 2 thiol end groups, which enables its chemical grafting to planar
      gold while retaining a free thiol group to attach nanoparticles. This step was
      optimized by varying experimental parameters such as solvent, temperature and
      immersion time. The grafting was monitored by polarization modulation infrared
      reflection absorption spectroscopy (PM-IRRAS) and X-ray photoelectron
      spectroscopy (XPS). The high resolution XPS sulfur peak made clear the existence
      of two contributions, S bound to gold and free S, thus led us to determine the
      optimal conditions to graft hexanedithiol in an extended conformation. 15 nm
      spherical gold nanoparticles were then immobilized on the resulting surface and
      their presence was evidenced by surface enhanced Raman spectroscopy (SERS) and
      atomic force microscopy (AFM). The resulting gold layer was used to build up a 3D
      biosensor by grafting protein A (PrA), rabbit immunoglobulin (rIgG), and bovine
      serum albumin (BSA), respectively. Each step was characterized by PM-IRRAS then
      compared to the results on planar gold surface. Despite the small size of
      particles and their rather low density on the planar surface, the amount of
      immobilized proteins, starting from PrA, was almost doubled. The amount of rIgG
      fixed on the 3D layer was also significantly increased ( approximately 4 times
      higher than on planar surfaces), however accompanied by a slight decrease of
      their accessibility, checked by assaying the recognition of a secondary IgG. This
      work demonstrates the feasibility and interest of building arrays of
      nanoparticles to immobilize molecular receptors; it also shows that controlling
      the conditions of elaboration of the biosensor at each step is determining for
      optimizing the number of molecular receptors.

PMID- 20692818
TI  - Preparation of bioinorganic fertilizing media by adsorption of humates on glassy
      aluminosilicates.
AB  - Surface-modified expanded perlite was synthesized using humic substances from the
      Megalopolis peaty lignite. Adsorption is efficient and increases at higher
      temperatures and lower pHs. The preparation can be carried out under mild
      conditions leading to an eco-friendly, bioinorganic material useful as soil
      conditioner and biofertilizer. Six adsorption models were applied; the Klotz,
      Freundlich and Redlich-Peterson isotherms fit more successfully to the
      experimental data. The obeying of the theoretical models was correlated with the
      heterogeneity and non-uniform distribution of the adsorption sites, host-guest
      attraction forces as well as the formation of self-assembled aggregates and self
      organized multilayers of humic substances onto the aluminosilicate adsorbent,
      consistent with changes in micromorphology. Thermodynamic quantities revealing
      distinct physicochemical characteristics of the adsorption phenomena, i.e.,
      enthalpy, entropy and free energy change, were calculated. Desorption experiments
      and cultivation of microorganisms demonstrated that perlite may act successfully
      as host material for microbial populations upgrading the humic-loaded perlite for
      soil applications.

PMID- 20692819
TI  - Conformational modifications of serum albumins adsorbed on different kinds of
      biomimetic hydroxyapatite nanocrystals.
AB  - Nanosized carbonate-hydroxyapatite represents a suitable material for bone
      substitution and delivery of biomolecules. Its interaction with serum proteins
      plays a central role in the process of implantation of a device. Herein, surface
      interactions of human (HSA) and bovine (BSA) serum albumin with two biomimetic
      carbonate-hydroxyapatites (CHA) differing for size, surface area, crystallinity
      degree and surface properties have been investigated. BSA reached a different
      maximum coverage, being higher with the CHA nanocrystals with the higher surface
      area, the smaller size, the lower crystallinity degree and the plate shape
      morphology. On the contrary, HSA did not show significant differences of maximum
      coverage on the two substrates. The adsorption isotherms have been fitted by the
      Langmuir and Freundlich models, showing that the biomimetic hydroxyapatite matrix
      behaves as a mixture of energetically homogeneous and heterogeneous sites due to
      its surface disorder. By using Fourier Transform Infrared Spectroscopy (FT-IR)
      and Circular Dichroism (CD) it has been found that CHAs affect the conformation
      of the adsorbed proteins. FT-IR spectroscopy shows that protein adhesion on CHA
      surface results in a significant reduction in helicity for both proteins on both
      substrates, as function of the coating extent as well as modification in the beta
      structures. CD spectroscopy of the HSA and BSA released in solution after
      desorption from the matrices shows that, while both proteins partially regain
      their helical structure, they show a distinct behaviour in their tertiary
      structure.

PMID- 20692820
TI  - Implications of abnormal pathology in fulminating colitis on the outcome of
      surgery.
AB  - BACKGROUND: The severe relapse of the diseases in patients with Crohn's disease
      or ulcerative colitis is associated with high morbidity and mortality. Early
      prediction for the failure of aggressive medical treatment and consequently,
      early surgical interference in cases with severe colitis and severe Crohn's
      colitis are supposed to be effective means for reducing these high rates.
      METHODS: Patients who presented at the Accident & Emergency Department with
      severe colitis and severe Crohn's colitis and on whom emergency colectomy was
      operated were identified and they formed the basis of this study. RESULTS:
      Patients (n=34) with acute fulminating colitis and their condition required
      emergency colectomy were seen over a period of 5 years. A strategy of early
      detection of cases of toxic dilatation and/or perforation proved efficient in
      reducing morbidity and mortality in cases of severe colitis. The mortality in the
      presented series was zero and the morbidity occurred mainly in such cases that
      presented with fulminant distal colitis, which was complicated by proximal faecal
      loading. CONCLUSION: Diagnosis of proximal faecal loading in cases with fulminant
      colitis is likely to be an indication for surgery. Further studies are required
      for confirming this conclusion.

PMID- 20692821
TI  - Emerging concepts in autoimmune encephalomyelitis beyond the CD4/T(H)1 paradigm.
AB  - Multiple sclerosis (MS) and its animal model experimental autoimmune
      encephalomyelitis (EAE) have long been regarded as primarily T helper cell type 1
      mediated diseases. However, recent evidence suggests that T(H)17 cells, a mostly
      unexplored subset of T helper cells, may be even more pathogenic than T(H)1
      cells. In the EAE model, this cell type is crucial for the recruitment of
      leukocytes into the CNS and for triggering parenchymal inflammation. In humans,
      T(H)17 cells are found in acutely active and on the borders of chronically active
      lesions. Overall, CD4(+) T cells only recognize antigens presented on MHC class
      II complexes, and these are seldom found in the CNS. MHC class I, in contrast,
      can be induced on neurons and myelin. This also makes CD8(+) T cells promising
      candidates as effector cell types. Indeed, CD8(+) T cells outnumber CD4(+) T
      cells in the lesions of MS patients, and can induce axonal pathology. New data on
      B cells have likewise stimulated unconventional paths of reasoning about the
      disease. B cells can contribute to the pathogenesis by secreting autoantibodies
      and presenting antigens to T cells. By the formation of ectopic B cell aggregates
      in the CNS, B cell differentiation and response can take place remote from the
      periphery, thus autonomously fueling pathology. In addition, cells of the innate
      immune system including macrophages, dendritic cells and mast cells are present
      in the inflamed CNS. On the one hand, these cells can recognize pathogen
      associated molecular patterns via Toll-like receptors (TLRs), generating
      proinflammatory signals that trigger adaptive immune responses. On the other
      hand, these cells support the autoimmune process by the secretion of effector
      molecules such as nitric oxide (NO). Apart from a solely pathogenic autoimmune
      role, regulatory T cells, NK cells and NKT cells can suppress autoreactive cells.
      In this paper, we review data on how a complex network of immune mechanisms is
      involved in the pathogenesis of MS and EAE. We also critically reevaluate the
      traditional CD4/T(H)1 paradigm.

PMID- 20692822
TI  - Short-term weight loss in overweight/obese low-income women improves plasma zinc
      and metabolic syndrome risk factors.
AB  - Metabolic syndrome is a group of disorders involving obesity, insulin resistance,
      dyslipidemia and hypertension. Obesity is the most crucial risk factor of
      metabolic syndrome, because it is known to precede other risk factors. Obesity is
      also associated with disturbances in the metabolism of the trace mineral, zinc.
      The overall purpose of this study was to investigate the effects of short-term
      weight loss on plasma zinc and metabolic syndrome risk factors. An 8-week weight
      loss intervention study was conducted with 90 low-income overweight/obese
      mothers, whose youngest child was 1-3 years old. Plasma levels of zinc, glucose,
      insulin, leptin, triglycerides, total, high-density lipoprotein (HDL) and low
      density lipoprotein (LDL) cholesterol were measured and compared at weeks 0 and 8
      of the weight loss program. At pre-study, plasma zinc was low in 39% and, within
      normal values in 46%, of obese/overweight mothers. By the end of intervention,
      plasma zinc rose by 22% and only 5% of the mothers continued to exhibit low
      plasma zinc. At post-study, the metabolic syndrome risk factors of waist
      circumference, HDL cholesterol, and diastolic blood pressure (p<0.05) showed
      significant improvements. Plasma zinc increased by a greater margin (67%) in
      women with low zinc, as compared to those with normal zinc (18%); weight
      reduction was similar in both the groups. Finally, changes in % body fat were
      related negatively with changes in plasma zinc (r=- 0.28, p<0.05). The
      circulating levels of zinc, as well as the metabolic syndrome components, showed
      significant improvements in overweight/obese low-income women after weight loss.

PMID- 20692823
TI  - Metabolic reconstruction, constraint-based analysis and game theory to probe
      genome-scale metabolic networks.
AB  - With the advent of modern omics technologies, it has become feasible to
      reconstruct (quasi-) whole-cell metabolic networks and characterize them in more
      and more detail. Computer simulations of the dynamic behavior of such networks
      are difficult due to a lack of kinetic data and to computational limitations. In
      contrast, network analysis based on appropriate constraints such as the steady
      state condition (constraint-based analysis) is feasible and allows one to derive
      conclusions about the system's metabolic capabilities. Here, we review methods
      for the reconstruction of metabolic networks, modeling techniques such as flux
      balance analysis and elementary flux modes and current progress in their
      development and applications. Game-theoretical methods for studying metabolic
      networks are discussed as well.

PMID- 20692825
TI  - Interscapular pain during cesarean delivery under epidural anesthesia.

PMID- 20692826
TI  - Spinal anaesthesia for caesarean section for a woman with von Hippel Lindau
      disease.

PMID- 20692827
TI  - Granisetron or ondansetron for prevention of subarachnoid morphine-induced
      pruritus after cesarean delivery.

PMID- 20692828
TI  - Receptor tyrosine kinase and downstream signalling analysis in diffuse malignant
      peritoneal mesothelioma.
AB  - Our aim was to assess the activation profile of EGFR, PDGFRB and PDGFRA receptor
      tyrosine kinases (RTK) and their downstream effectors in a series of
      cryopreserved diffuse malignant peritoneal mesothelioma (DMPM) surgical specimens
      to discover the targets for drug inhibition. We also made a complementary
      analysis of the cytotoxic effects of some kinase inhibitors on the proliferation
      of the human peritoneal mesothelioma STO cell line. We found the
      expression/phosphorylation of EGFR and PDGFRB in most of the tumours, and PDGFRA
      activation in half. The expression of the cognate ligands TGF-alpha, PDGFB and
      PDGFA in the absence of RTK mutation and amplification suggested the presence of
      an autocrine/paracrine loop. There was also evidence of EGFR and PDGFRB co
      activation. RTK downstream signalling analysis demonstrated the
      activation/expression of ERK1/2, AKT and mTOR, together with S6 and 4EBP1, in
      almost all the DMPMs. No KRAS/BRAF mutations, PI3KCA mutations/amplifications or
      PTEN inactivation were observed. Real-time polymerase chain reaction revealed the
      decreased expression of TSC1 c-DNA in half of the tumours. In vitro cytotoxicity
      studies showed the STO cell line to be resistant to gefitinib and sensitive to
      sequential treatment with RAD001 and sorafenib; these findings were consistent
      with the presence of the KRAS mutation G12D in these cells although it was not
      detectable in the original tumour. Our results highlight the ligand-dependent
      activation and co-activation of EGFR and PDGFRB, as well as a connection between
      these activated RTKs and the downstream mTOR pathway, thus supporting the role of
      combined treatment with RTK and mTOR inhibitors in DMPM.

PMID- 20692829
TI  - Allicin and derivates are cysteine protease inhibitors with antiparasitic
      activity.
AB  - Allicin and derivatives thereof inhibit the CAC1 cysteine proteases falcipain 2,
      rhodesain, cathepsin B and L in the low micromolar range. The structure-activity
      relationship revealed that only derivatives with primary carbon atom in vicinity
      to the thiosulfinate sulfur atom attacked by the active-site Cys residue are
      active against the target enzymes. Some compounds also show potent antiparasitic
      activity against Plasmodium falciparum and Trypanosoma brucei brucei.

PMID- 20692830
TI  - Preparation of 4,7-diphenyl-1,10-phenanthroline-2,9-dicarboxylic acid catalyzed
      by iron(III)porphyrins with (diacetoxyiodo)benzene.
AB  - Using iron(III)porphyrins in combination with (diacetoxyiodo)benzene allows for
      the conversion of 2,9-bis(bromomethyl)-4,7-diphenyl-1,10-phenanthroline into 4,7
      diphenyl-1,10-phenanthroline-2,9-dicarboxylic acid. This method provides a cost
      effective and environmentally-friendly oxidation procedure using less toxic
      PhI(OAc)2 and biologically relevant iron(III)porphyrins. The catalytic activity
      of five kinds of iron-metallated functional porphyrins were investigated using
      different oxidants, including air, H2O2, PhI(OAc)2, PhIO and NaClO. Our results
      showed that the use of T(p-NO2)PPFeCl with PhI(OAc)2 as the oxidant in the
      presence of water displays remarkable activity for the desired oxidation
      reaction. The generality of this method was examined by synthesizing the
      carboxylic acids of pyridines and quinolines.

PMID- 20692831
TI  - Relationships between structures of hydroxyflavones and their antioxidative
      effects.
AB  - Even hydroxyflavones show diverse biological functions, they have two common
      features such as showing antioxidative effects and containing hydroxyl groups.
      The authors tested the antioxidative effects of thirty hydroxyflavones using 1,1
      diphenyl-2-picrylhydrazyl radical scavenging assay. While the scavenging activity
      of galangin, 3,5,7-trihydroxyflavone was 52.5%, fisetin, 3,7,3',4'
      tetrahydroxyflavone showed 85.2%. To investigate the relationships between the
      structures of hydroxyflavones and their antioxidative effects, the three
      dimensional quantitative structure-activity relationships were examined.

PMID- 20692832
TI  - Identification of a novel NR2B-selective NMDA receptor antagonist using a virtual
      screening approach.
AB  - We report the identification of a novel NR2B-selective NMDAR antagonist with an
      original scaffold, LSP10-0500. This compound was identified by a virtual high
      throughput screening approach on the basis of a quantitative pharmacophore model
      of NR2B-specific NMDAR antagonists. A SAR study around LSP10-0500 is also
      described.

PMID- 20692833
TI  - N-tetrahydrothiochromenoisoxazole-1-carboxamides as selective antagonists of
      cloned human 5-HT2B.
AB  - The serendipitous discovery of N-cyclohexyl-8-fluoro-3,3a,4,9b-tetrahydro-1H
      thiochromeno[4,3-c]isoxazole-1-carboxamide as a selective human serotonin 5-HT2B
      antagonist with Ki of 42+/-5 nM is reported herein. A subsequent functional assay
      indicated little agonist activity compared to 5-HT itself.

PMID- 20692834
TI  - Discovery of biphenylketones as dual modulators of inflammation and bone loss.
AB  - Biphenylketones were identified as novel inhibitors of NFkappaB activation.
      Structure-activity studies led to the identification of compound 4c, which had
      good potency against osteoclasts (IC50=0.8 microM), showed oral activity, and was
      able to completely prevent inflammation and bone loss in vivo.

PMID- 20692835
TI  - Selectivity improvement of an azole inhibitor of CYP707A by replacing the
      monosubstituted azole with a disubstituted azole.
AB  - The plant growth-retardant uniconazole (UNI), a triazole inhibitor of gibberellin
      biosynthetic enzyme (CYP701A), inhibits multiple P450 enzymes including ABA 8'
      hydroxylase (CYP707A), a key enzyme in ABA catabolism. Azole P450 inhibitors bind
      to a P450 active site by both coordinating to the heme-iron atom via sp2 nitrogen
      and interacting with surrounding protein residues through a lipophilic region. We
      hypothesized that poor selectivity of UNI may result from adopting a distinct
      conformation and orientation for different active sites. Based on this
      hypothesis, we designed and synthesized novel UNI analogs with a disubstituted
      azole ring (DSI). These analogs were expected to have higher selectivity than UNI
      because the added functional group may interact with the active site to restrict
      orientation of the molecule in the active site. DSI-505ME and DSI-505MZ, which
      have an imidazolyl group with a methyl 5-acrylate, strongly inhibited recombinant
      CYP707A3, with no growth-retardant effect.

PMID- 20692836
TI  - [3-azabicyclo[3.1.0]hex-1-yl]phenyl-benzenesulfonamides as selective dopamine D3
      antagonists.
AB  - A new class of azabicyclo[3.1.0]benzenesulfonamides is presented as selective
      dopamine D3 antagonists together with SAR and selectivity data.

PMID- 20692837
TI  - A new distal myopathy with mutation in anoctamin 5.
AB  - We have been following clinically and with muscle MRI for the past 3-decades a
      Finnish family with two patients with distal muscular dystrophy. Previously we
      demonstrated the cellular defect in these patients to be defective membrane
      repair and more recently have identified the causative gene to be anoctamin 5
      (ANO5). The disorder seen in these patients is characterized by onset in the
      third decade. First symptoms were burning sensation on the calves and later on
      calf tightness during running. Muscle weakness and wasting were asymmetric and
      early involving the calf muscles, later spread to the thigh muscles. Biceps
      brachi was later manifestation. Clinical course was slow. CK levels were high.
      Muscle biopsy showed dystrophic pattern and multifocal disruption of the
      sarcolemmal membrane but no subsarcolemmal vesicle accumulation nor active
      inflammation. We conclude that the disease seen in our cases is a new separate
      clinical, genetic and histopathologic entity to include within the classification
      of autosomal recessive distal muscular dystrophies.

PMID- 20692838
TI  - Probiotics and diarrhoea management in enterally tube fed critically ill patients
      -what is the evidence?
AB  - OBJECTIVE: The aim of this literature review is to identify the role of
      probiotics in the management of enteral tube feeding (ETF) diarrhoea in
      critically ill patients. BACKGROUND: Diarrhoea is a common gastrointestinal
      problem seen in ETF patients. The incidence of diarrhoea in tube fed patients
      varies from 2% to 68% across all patients. Despite extensive investigation, the
      pathogenesis surrounding ETF diarrhoea remains unclear. Evidence to support
      probiotics to manage ETF diarrhoea in critically ill patients remains sparse.
      METHOD: Literature on ETF diarrhoea and probiotics in critically ill, adult
      patients was reviewed from 1980 to 2010. The Cochrane Library, Pubmed, Science
      Direct, Medline and the Cumulative Index of Nursing and Allied Health Literature
      (CINAHL) electronic databases were searched using specific inclusion/exclusion
      criteria. Key search terms used were: enteral nutrition, diarrhoea, critical
      illness, probiotics, probiotic species and randomised clinical control trial
      (RCT). RESULTS: Four RCT papers were identified with two reporting full studies,
      one reporting a pilot RCT and one conference abstract reporting an RCT pilot
      study. A trend towards a reduction in diarrhoea incidence was observed in the
      probiotic groups. However, mortality associated with probiotic use in some
      severely and critically ill patients must caution the clinician against its use.
      CONCLUSION: Evidence to support probiotic use in the management of ETF diarrhoea
      in critically ill patients remains unclear. This paper argues that probiotics
      should not be administered to critically ill patients until further research has
      been conducted to examine the causal relationship between probiotics and
      mortality, irrespective of the patient's disease state or projected prophylactic
      benefit of probiotic administration.

PMID- 20692839
TI  - Functional analysis on the treatment of torn discoid lateral meniscus.
AB  - The purpose of this study is to evaluate the functional outcome on the treatment
      of torn discoid lateral meniscus. Thirty-two torn discoid lateral meniscuses in
      29 patients were retrospectively reviewed. There were 13 males and 16 females
      with a mean age of 31.3+/-17.0. The age distribution were 24% in pediatric age (<
      11 years old), 38%in young adult under 25 years and 38% in 25 years and older.
      Subjective symptoms included pain in 63%, popping and snapping in 56%, locking in
      41%, givingway in 17%; and objective signs included decreased knee motion in 16%.
      Partial lateral menisectomy and saucerization were performed in 18 knees (56%),
      meniscus repairs were done in eight knee (25% ) and subtotal lateral menisectomy
      in six knees (19%). At an average follow up of 52.5+/-25.9 months (24-96 months).
      The results showed 84% good to excellent, 16% fair, and none poor. No significant
      difference was noted on the outcomes of different treatment methods. The age of
      symptom onset and the time of operation correlated with the IKDC and Tenger
      score. (p<0.001). Our data showed symptomatic torn discoid lateral meniscus may
      manifest at any age from childhood to adult. The first manifestation of symptom
      before age 11 year old was observed in only 24%. Therefore, discoid lateral
      meniscus should not be considered a childhood disease.

PMID- 20692840
TI  - Design, synthesis, and biological evaluation of conformationally constrained
      glycerol 3-phosphate acyltransferase inhibitors.
AB  - Glycerol 3-phosphate acyltransferase (GPAT) isozymes are central control points
      for fat synthesis in mammals. Development of inhibitors of these membrane-bound
      enzymes could lead to an effective treatment for obesity, but is thwarted by an
      absence of direct structural information. Based on a highly successful study
      involving conformationally constrained glycerol 3-phosphate analogs functioning
      as potent glycerol 3-phosphate dehydrogenase inhibitors, several series of cyclic
      bisubstrate and transition state analogs were designed, synthesized, and tested
      as GPAT inhibitors. The weaker in vitro inhibitory activity of these compounds
      compared to a previously described benzoic acid series was then examined in
      docking experiments with the soluble squash chloroplast GPAT crystal structure.
      These in silico experiments indicate that cyclopentyl and cyclohexyl scaffolds
      prepared in this study may be occluded from the enzyme active site by two protein
      loops that sterically guard the phosphate binding region. In view of these
      findings, future GPAT inhibitor design will be driven toward compounds based on
      planar frameworks able to slide between these loops and enter the active site,
      resulting in improved inhibitory activity.

PMID- 20692841
TI  - A class of novel carboline intercalators: Their synthesis, in vitro anti
      proliferation, in vivo anti-tumor action, and 3D QSAR analysis.
AB  - Based on DOCK scores 18 N-(3-benzyloxycarbonylcarboline-1-yl)ethylamino acid
      benzylesters (6a-r) were synthesized as anti-tumor agents. Their IC(50) values
      against five human carcinoma cell lines ranged from 11.1muM to more than 100muM.
      The in vivo assay identified five derivatives of them had no anti-tumor action,
      the anti-tumor activity of nine derivatives of them equaled that of cytarabine,
      and the anti-tumor activity of three derivatives of them was higher than that of
      cytarabine. The UV and fluorescence spectra, as well as the relative viscosity
      and melting temperature measurements of calf thymus DNA (CT DNA) with and without
      the representative compound suggested that DNA intercalation could be their
      action mechanism. The 3D QSAR analysis of N-(3-benzyloxycarbonylcarboline-1
      yl)ethylamino acid benzylesters (6a-r) revealed that their in vivo anti-tumor
      activity significantly depends on the molecular electrostatic and steric fields
      of the side chain of the amino acid residue.

PMID- 20692842
TI  - A small high sensitivity neutron detector using a wavelength shifting fiber.
AB  - A small neutron detector using an optical fiber was previously developed for
      reaction rate measurements at research reactors and accelerator facilities. This
      detector can be inserted into narrow spaces and its spatial resolution is less
      than 1mm; however, its neutron sensitivity is low because of the small size of
      its detector. The purpose of this study is to develop a new optical fiber
      detector with high neutron sensitivity by using a wavelength shifting fiber.
      Through the measurement of the reaction rate distribution in a reactor core, we
      found that it is possible to increase the effective length of the detector,
      resulting in increased neutron sensitivity compared with a conventional optical
      fiber detector. Additionally, using a longer wavelength shifting fiber, the
      sensitivity can be increased until it is as large as that of a typical small
      BF(3) proportional counter, which means that this detector can be used for even
      low neutron flux fields.

PMID- 20692843
TI  - Therapy of the osteoarthritis of the temporomandibular joint.
AB  - Osteoarthritis is a common condition of the mandible. The treatment of
      osteoarthritis primarily consists of rest therapy (restricting jaw movements),
      the use of pharmaceuticals (analgesics, antiinflammatories), splint therapy,
      thermotherapy or mini-invasive therapy. Our study investigated the effectiveness
      of the various therapeutic options in the treatment of osteoarthritis. We
      compared the effectiveness of rest therapy (restricting mouth opening, analgesic
      therapy), splints, arthrocentesis of the upper joint space, and arthrocentesis in
      combination with splint therapy. We looked at 80 patients diagnosed with
      osteoarthritis of the temporomandibular joint. We only included patients with
      symptoms in one temporomandibular joint (TMJ). This 3 months long-term study
      shows that arthrocentesis combined with the use of a splint is an effective first
      stage treatment method for patients with osteoarthritis of the TMJ (80% patients
      with good outcome 3 months after commencement of therapy).

PMID- 20692844
TI  - How successful is lung-preserving radical surgery in the mesothelioma and radical
      surgery-trial environment? A case-controlled analysis.
AB  - OBJECTIVE: To determine whether there is a survival benefit from open-lung
      preserving surgery (radical decortication) for malignant mesothelioma, when
      compared with the non-radical approach in the mesothelioma and radical surgery
      (MARS)-trial era. METHODS: We compared outcomes between 13 patients with
      malignant mesothelioma, who underwent radical decortication (group RD, n = 13)
      with 13 case-matched patients, who had palliative surgery (group non-radical
      decortication (NRD), n = 13) over a period of 2 years from June 2006 onwards.
      Patients were matched for age, sex, histology, computed tomography (CT) stage,
      haematological indices, body mass index (BMI) and adjuvant chemotherapy. We
      compared perioperative and postoperative courses and long-term survival. RESULTS:
      Histology was 25% biphasic and 75% epithelioid in both the groups. There was no
      significant difference in the proportions receiving adjuvant chemotherapy (54%, p
      = 1.00), but more patients in the RD group received adjuvant radiotherapy (46% vs
      15%, p = 0.20). Median survival was higher for all cell types in the RD group
      (16.9 months vs 6.8 months, p = 0.001). CONCLUSION: Radical open-lung-sparing
      surgery may confer a survival advantage to patients with malignant mesothelioma,
      who are fit to undergo radical decortication followed by chemotherapy and
      radiotherapy. Trials of radical surgery versus no surgery should include lung
      sparing operations.

PMID- 20692845
TI  - Delayed type A aortic dissection after successful endovascular repair of a
      chronic type B dissection.

PMID- 20692846
TI  - Is interleukin-10 the only predictor for inflammation?

PMID- 20692848
TI  - In vitro photodynamic antimicrobial activity of methylene blue and endoscopic
      white light against Helicobacter pylori 26695.
AB  - Photodynamic therapy (PDT) is a method for inactivating cells (viral, bacterial
      and cancer cells) using photosensitizers (PS) and light of various wavelengths.
      Helicobacter pylori might be easily affected by light because it has few genes to
      repair light-induced DNA damage. In vitro PDT against H. pylori was conducted
      using endoscopic white light and methylene blue (MB) as the PS before application
      to in vivo study. The bactericidal effects were measured by counting viable cells
      after PDT. The degree of oxidative damage of DNA was confirmed using alkaline gel
      electrophoresis, real-time PCR (RT-PCR) and an assay of 8-hydroxy-2
      deoxyguanosine (8-OHdG). In the control group, the number of viable cells was
      maintained constantly during the experiment. In the groups treated with either
      0.2mg/mlMB alone or white light with 0.02mg/mlMB for 10min, bacteria decreased
      approximately a hundredfold. The killing effect increased proportionally to the
      PS concentration and the duration of irradiation. DNA damage by PDT proven by
      alkaline gel electrophoresis, RT-PCR and assay of 8-OHdG, was greater in PDT
      treated groups than in control. PDT using MB and endoscopic white light showed
      effective bactericidal activity in vitro by oxidative DNA damage of H. pylori.

PMID- 20692849
TI  - Temperature benefits the photosynthetic performance of the diatoms Chaetoceros
      gracilis and Thalassiosira weissflogii when exposed to UVR.
AB  - The aim of this study was to assess the combined effects of temperature and UVR
      on the photosynthesis performance of two diatoms -Chaetoceros gracilis and
      Thalassiosira weissflogii. In particular, we evaluated the role of UVR in
      inducing photoinhibition and the potential mitigation of this negative effect by
      an increase in temperature. Cultures were pre-acclimated at two temperatures - 18
      degrees C and 23 degrees C - and exposed to different radiation treatments -
      UVR+PAR (280-700nm); UV-A+PAR (315-700nm) and PAR only (400-700nm) under two
      temperatures: 18 degrees C (local surface summer water temperature) and 23
      degrees C (simulating a potential increase estimated by the year 2100). Exposure
      to natural solar radiation resulted in UVR-induced photoinhibition that was
      significantly higher in T. weissflogii than in C. gracilis. Both species
      benefited from the higher temperature (23 degrees C) resulting in a lower
      photoinhibition as compared to samples exposed at 18 degrees C. Inter-specific
      differences were determined in regard to the heat dissipation processes (NPQ)
      which were higher at high temperatures, and much more evident in C. gracilis than
      in T. weissflogii. The analyses of inhibition and recovery rates under different
      irradiances indicate that the balance between negative (inhibition) and positive
      (repair-dissipation) effects shifted towards a more positive balance with
      increasing temperature. Our results highlight for a beneficial effect of
      temperature on photosynthesis performance during exposure to UVR, although
      important inter-specific differences are found, probably due to differences in
      cell size as well as in their distribution within the oceanic realm (i.e.,
      coastal versus oceanic species).

PMID- 20692850
TI  - Novel fluorescent conjugate containing glucose and NBD and its carrier-mediated
      uptake by tobacco cells.
AB  - Some compounds that contain glucose groups can be transported across the plasma
      membrane into the cells through hexose transporters. To test the hypothesis that
      glucose-conjugated insecticides also have similar uptake and translocation
      properties, a novel fluorescent conjugate (12) was prepared by conjugating
      glucose and 7-nitrobenz-2-oxa-1,3-diazole with 4-iodo-1-phenylpyrazoles. Its
      fluorescence spectra and uptake by suspension-cultured tobacco (Nicotiana tabacum
      L.cv.) cells were studied. The fluorescence spectra showed long wavelengths with
      maximum emission at 530nm. After incubating tobacco cell suspensions in 10MUM
      conjugate for 0.5h, green fluorescence of 12 was clearly visible in the cells
      under fluorescence microscopy. After 2h of incubation, more than 70% of 12 was
      absorbed. Carbonyl cyanide m-chlorophenylhydrazone, phloridzin and glucose
      drastically inhibited uptake. In concentration-dependent uptakes, the uptake rate
      of 12 showed a saturable component and was in accordance with Michaelis-Menten
      kinetics. The results proved that the glucose moiety can guide 12 into tobacco
      cells and that hexose transporters mediated the uptake.

PMID- 20692851
TI  - On-line bioaffinity-electrospray mass spectrometry for simultaneous detection,
      identification, and quantification of protein-ligand interactions.
AB  - We describe here an on-line combination of a surface acoustic wave (SAW)
      biosensor with electrospray ionization mass spectrometry (SAW-ESI-MS) that
      enables the direct detection, identification, and quantification of affinity
      bound ligands from a protein-ligand complex on a biosensor chip. A trapping
      column was used between the SAW-biosensor and the electrospray mass spectrometer
      equipped with a micro-guard column, which provides simultaneous sample
      concentration and desalting for the mass spectrometric analysis of the
      dissociated ligand. First applications of the on-line SAW-ESI-MS combination
      include (1), differentiation of beta-amyloid (Abeta) epitope peptides bound to
      anti-Abeta antibodies; (2), the identification of immobilized Substance P peptide
      calmodulin complex; (3), identification and quantification of the interaction of
      3-nitrotyrosine-modified peptides with nitrotyrosine-specific antibodies; and
      (4), identification of immobilized anti-alpha-synuclein-human alpha-synuclein
      complex. Quantitative determinations of protein-ligand complexes by SAW yielded
      dissociation constants (K(D)) from micro-to low nanomolar sample concentrations.
      The on-line bioaffinity-ESI-MS combination presented here is expected to enable
      broad bioanalytical application to the simultaneous, label-free determination and
      quantification of biopolymer-ligand interactions, as diverse as antigen-antibody
      and lectin-carbohydrate complexes.

PMID- 20692852
TI  - Toward total structural analysis of cardiolipins: multiple-stage linear ion-trap
      mass spectrometry on the [M - 2H + 3Li]+ ions.
AB  - ESI multiple-stage linear ion-trap (LIT) mass spectrometric approaches for a near
      complete structural characterization of cardiolipins (CLs), including
      identification of the fatty acyl substituents, assignment of the fatty acid
      substituents on the glycerol backbone, and location of the double-bond(s) or
      cyclopropyl group along the fatty acid chain are described. Upon collisionally
      activated dissociation (CAD) on the [M - 2H + 3Li](+) ions of CL in an ion-trap
      (MS(2)), two sets of fragment ions (designated as (a + 136) and (b + 136) ions)
      analogous to those previously reported for the [M - 2H + 3Na](+) ions were
      observed, leading to assignment of the phosphatidyl moieties attached to 1'- or
      3'-position of the central glycerol. Further dissociation of the (a + 136) (or (b
      + 136)) ions (MS(3)) gives rise to the (a + 136 - R(1(or 2))CO(2)Li) (or b + 136 
      R(1(or 2))CO(2)Li) ion pairs that identify the fatty acid moieties and their
      position on the glycerol backbone. This is followed by MS(4) on the (a + 136 -
      R(1(or 2))CO(2)Li) (or b + 136 - R(1(or 2))CO(2)Li) ion to eliminate a tricyclic
      glycerophosphate ester residue (136 Da) to yield the (a - R(1(or 2))CO(2)Li) ion,
      which is then subjected to MS(5). The MS(5) spectrum contains the structural
      information that locates the double-bond(s) or cyclopropyl group of the fatty
      acid substituents. Finally, the subsequent MS(6) on the dilithiated fatty acid
      ions generated from MS(5) also yields feature ions that confirm the assignment.

PMID- 20692853
TI  - High-frequency AC electrospray ionization source for mass spectrometry of
      biomolecules.
AB  - A novel high-frequency alternating current (AC) electrospray ionization (ESI)
      source has been developed for applications in mass spectrometry. The AC ESI
      source operates in a conical meniscus mode, analogous to the cone-jet mode of
      direct current (DC) electrosprays but with significant physical and mechanistic
      differences. In this stable conical-meniscus mode at frequencies greater than 50
      kHz, the low mobility ions, which can either be cations or anions, are entrained
      within the liquid cone and ejected as droplets that eventually form molecular
      ions, thus making AC ESI a viable tool for both negative and positive mode mass
      spectrometry. The performance of the AC ESI source is qualitatively shown to be
      frequency-dependent and, for larger bio-molecules, the AC ESI source produced an
      ion signal intensity that is an order of magnitude higher than its DC
      counterpart.

PMID- 20692854
TI  - Factors influencing cooperation among healthcare providers in a community-based
      stroke care system in Japan.
AB  - Community-based stroke care in Japan is currently provided in acute hospitals,
      convalescent rehabilitation units, general practices, sanatorium-type wards,
      nursing care facilities, and in-home/commuting care services. We conducted a
      nationwide survey to identify factors influencing cooperation among the various
      providers of community-based stroke care. We sent questionnaires to 11,178
      facilities and assessed the independent variables of excellent and fair
      cooperation among the care providers. Of the providers that responded, 66% were
      engaged in medical practice or long-term care for stroke patients. The following
      independent variables were inversely associated with excellent or fair
      cooperation in the community: area with the higher population density among 3
      groups divided by tertile threshold (odds ratio [OR], 0.53; 95% confidence
      interval [CI], 0.41-0.69), facilities covered by long-term care insurance (OR,
      0.27; 95% CI, 0.22-0.34), and insufficient communication with local government
      (OR, 0.19; 95% CI, 0.14-0.24). Positive independent variables of excellent or
      fair cooperation were the sharing of patient information in the community (OR,
      2.53; 95% CI, 1.78-3.66), use of a scale for assessing activities of daily living
      (OR, 1.93; 95% CI, 1.42-2.63), appropriate utilization of care support managers
      (OR, 1.91; 95% CI, 1.43-2.55), and adequate comprehension of the long-term care
      insurance system (OR, 1.54; 95% CI, 1.24-1.92). Our findings suggest that
      improved communication between healthcare providers and local government, along
      with appropriate attention to the problems facing providers covered by long-term
      care insurance, may improve community-based stroke care in Japan.

PMID- 20692855
TI  - High proportion of lacunar strokes at night: the Bergen stroke study.
AB  - The main objective of this study was to investigate the circadian distribution of
      subtypes of ischemic stroke. The time of onset of stroke in consecutive stroke
      patients was registered and categorized into the following time intervals:
      midnight-6 am, 6 am-noon, noon-6 pm, and 6 pm-midnight. Patients with unknown
      onset of stroke were categorized as woke up with stroke, found with stroke by
      others, and miscellaneous. Patients who woke up with stroke, were included in the
      midnight-6 am interval. Stroke subtypes were categorized according to the Trial
      of ORG 10172 in Acute Stroke Treatment (TOAST) criteria and as lacunar or embolic
      stroke based on diffusion-weighted magnetic resonance imaging (DWI). The study
      group comprised 1101 patients who sustained ischemic stroke between February 2006
      and March 2008. The proportion of lacunar stroke, defined according to both the
      TOAST criteria and DWI findings, was significantly higher in the midnight-6 am
      interval compared with the other time intervals. In our study group, the
      prevalence of lacunar strokes was highest at night.

PMID- 20692856
TI  - Cardiac papillary fibroelastoma: source of cerebral embolism treated with
      intravenous thrombolysis.
AB  - We present the case of a 41-year-old man with sudden development of left
      hemiparesis due to infarction of the right middle cerebral artery that was
      successfully treated with intravenous (IV) thrombolysis with alteplase.
      Transthoracic echocardiography showed a small mass in the left ventricle. The
      patient underwent surgical resection, and histological examination of the mass
      confirmed the diagnosis of papillary fibroelastoma. It remains to be investigated
      whether heart ultrasound evaluation should be performed before IV thrombolysis in
      selected patients with stroke, given the apparently increased risk of bleeding.
      However, IV thrombolysis should not be postponed due to a lengthy investigation,
      because of its potential for reducing morbidity in patients with stroke.

PMID- 20692857
TI  - Use of small ruminant lentivirus-infected rams for artificial insemination.
AB  - The presence of proviral DNA, mRNA transcripts and/or viral proteins in small
      ruminant lentiviral infections may be intermittent. The aim of this study was to
      identify methods of avoiding small ruminant lentivirus (SRLV) transmission to
      ewes when using infected rams in artificial insemination (AI). Semen from rams,
      seropositive and PCR-positive in blood but consistently negative for both
      proviral DNA and viral protein expression in semen, was used to artificially
      inseminate 19 ewes. Follow-up investigation of these ewes and of two of their
      offspring indicated that under the study conditions virus transmission through
      insemination did not occur. These preliminary findings suggest that semen from
      SRLV-infected rams could be used for AI without the risk of transmitting virus to
      susceptible ewes or their lambs. Further larger studies will be required to
      confirm this finding.

PMID- 20692858
TI  - Two novel mutations of SCN9A (Nav1.7) are associated with partial congenital
      insensitivity to pain.
AB  - Insensitivity to pain is a rare disorder that is commonly associated with
      Hereditary Sensory and Autonomic Neuropathies (HSAN I-V) resulting often in
      autonomic dysfunction and premature death. Very few individuals have been
      reported with pain insensitivity lacking such autonomic neuropathies. We
      performed genetic, neurologic, psychological, and psychophysical evaluations in
      such an individual (OMIM 243000) and her first degree relatives. Sequence
      analysis of genomic DNA revealed two novel SCN9A mutations in this index case
      (IC). One was a non-conservative missense mutation (C1719R) in exon 26 present
      only in the IC and one parent. Further sequence analysis of the child's DNA
      revealed a 1-bp splice donor deletion in intron 17 which was also present in the
      other parent and one sibling. Detailed psychophysical testing was used to
      phenotypically characterize the IC, her family members, and 10 matched normal
      controls. Similar to family members and controls the IC showed normal
      somatosensory functioning for non-nociceptive mechanoreception and warmth.
      However, she demonstrated diminished ability to detect cool temperatures combined
      with profound deficits in heat and mechanical nociception. Congenital
      insensitivity to pain in our IC was associated with two novel SCN9A mutations
      which most likely resulted in a Nav1.7 channelopathy. However, in contrast to
      individuals with other SCN9A mutations, the observed pain insensitivity was
      relative and not absolute, which may be consistent with hypomorphic effects of
      one or both mutations. The ability to sense at least some danger signals may be
      advantageous and ameliorate the otherwise increased morbidity and mortality of
      some individuals with congenital insensitivity to pain.

PMID- 20692859
TI  - Exact solution to the Bloch equations and application to the Hahn echo.
AB  - The exact symbolic solution of the Bloch equations is given in the Lagrange form
      and illustrated with R2 experiments using a Hahn echo. Two different methods are
      also applied to approximately solve the Bloch equations, we find that splittings
      with effective-field interpretations are very substantially better than other
      approximations by comparing the errors. Estimates of transverse relaxation, R2,
      from Hahn echos are effected by frequency offset and field inhomogeneity. We use
      exact solutions of the Bloch equations and simulations to quantify both effects,
      and find that even in the presence of expected B0 inhomogeneity, off-resonance
      effects can be removed from R2 measurements, when?omega??0.5gammaB1, by fitting
      the exact solutions of the Bloch equations. Further, the experiments and
      simulations show that the fitting models with the exact solutions of the Bloch
      equations do not depend on the sampling density and delay times.

PMID- 20692860
TI  - Multicentre age-related reference intervals for cerebrospinal fluid serine
      concentrations: implications for the diagnosis and follow-up of serine
      biosynthesis disorders.
AB  - The disorders of serine biosynthesis are a group of inborn errors of metabolism
      characterised by congenital microcephaly, seizures and severe psychomotor
      retardation. Although these disorders are rare the prompt recognition of serine
      deficiency is important as these disorders are treatable. The diagnosis is based
      on decreased concentrations of serine in cerebrospinal fluid (CSF). It has
      previously been reported that CSF serine concentrations are inversely associated
      with age. However, accurate age-related reference intervals have not been
      generated which has contributed to cases not being identified. In a multicentre
      study involving 9 different laboratories a total of 424 CSF serine results were
      obtained. Regression based analyses were performed to calculate age-specific
      reference intervals. Lower reference intervals for subjects aged 1week, 1month,
      6months, 1year, 3years and 15years were 35.0, 31.0, 26.0, 24.0, 21.0 and
      17.0MUmol/L respectively. Assessment of CSF serine concentrations in 11 patients
      (aged 1day to 13years) previously diagnosed with disorders of serine biosynthesis
      (serine concentrations ranging from 5 to 18MUmol/L) were clearly decreased
      compared to our age-related reference intervals and would have correctly
      identified all cases, thus enabling prompt treatment. However, if age had not
      been taken into consideration a reference interval of 12.6-69.4MUmol/L would be
      obtained for the combined data set and would have resulted in 2 cases being
      missed. In conclusion, appropriate age-related reference intervals for CSF serine
      should be used to diagnose patients with inborn errors of serine biosynthesis.

PMID- 20692861
TI  - [Costs and adherence to antiretroviral treatment].
AB  - OBJECTIVE: To develop a system of data management that allows us to estimate the
      comparative effectiveness of the various antiretroviral treatment (ART) regimens.
      METHOD: Retrospective observational study in patients infected with HIV with
      stable ART. Adherence to treatment and unit cost for each patient's treatment was
      determined. The cost/patient/day was calculated and, multiplying by an adherence
      factor (fADH), the (cost/patient/day)(ADH). The comparison of both allowed us to
      obtain the Deltacost/patient, which estimates the additional costs caused by lack
      of adherence. The incremental cost-effectiveness (iCER), grouping the results by
      the various coformulated drugs ("combos"). A study of the budgetary impact of
      these combos was carried out. RESULTS: 468 patients were evaluated (62%
      adherent). Average adherence was 88+/-18%. The average value of
      (cost/patient/day) (ADH) was significantly higher than the cost/patient/day
      (27.3+/-9.8? compared to 24.3+/-7.6?. p<0.001). Just as with the f(ADH), no
      differences were found in the Deltacost/patient between the different ART
      combinations. The combo with the least deviation from the cost/patient/day due to
      lack of adherence was that composed of abacavir/zedovudine/lamivudine
      (ABC/AZT/3TC,Deltacost/patient=8.72+/-14.18%), and that with the greatest
      deviation AZT/3TC (Deltacost/patient=13.52+/-17.68%). No significant differences
      were found in the iCER calculated for any combo. The ART that included
      abacavir/lamivudine (ABC/3TC) obtained the least budgetary impact. CONCLUSIONS:
      The greatest cost and percentage of adherent patients associated with the combos
      composed of Tenovovir/Emtricitabine(TDF/FTC) and ABC/3TC, and the least cost and
      effectiveness of those composed of AZT/#TC and ABC/AZT/3TC, does not allow us to
      identify any option as significantly dominant. The regimens with ABC/3TC were
      shown to be the most favourable from the combined point of view of cost and
      adherence.

PMID- 20692862
TI  - [Quality of records in OMI-AP of the patients with stroke followed in primary
      care].
AB  - OBJECTIVES: 1) To determine the level of registration and control of
      cardiovascular risk factors in stroke patients treated in primary care in Murcia
      through electronic medical records. 2) To describe the registered drug treatment
      in patients with stroke. MATERIAL AND METHODS: Observational descriptive,
      retrospective, evaluated through the records in OMI (electronic medical records)
      in all areas of Murcia Health Service. A sample of 407 patients with stroke was
      analyzed. The analyzed variables were type of stroke, time of evolution,
      registered cardiovascular risk factors, registered cardiovascular disease,
      medication and degree of control of modifiable risk factors. RESULTS:
      Cardiovascular risk factors recorded were hypertension (81.1%), dyslipemia
      (72.5%), diabetes (41.3%), abdominal obesity (22.9%) and tobacco (8.8%).
      Registered cardiovascular diseases were ischemic heart disease (22.1%), atrial
      fibrillation (13.8%), nephropathy (11.8%), myocardial infarction (5.7%) and left
      ventricular hypertrophy (3.4%). 2.5% (10) of patients met all criteria for good
      control. The LDL cholesterol was controlled (<100mg/dl) and recorded in 24.8% of
      patients and blood pressure in 41.3%. 78.1% of patients were being treated with
      antihypertensive drugs, 47.4% with lipid-lowering drugs, and 79.1% with
      antiplatelet or anticoagulant. CONCLUSIONS: According to data recorded at OMI-AP
      the patients who have suffered a stroke have poor control of cardiovascular risk
      factors.

PMID- 20692863
TI  - [Which assisted reproduction technique as a function of sperm morphology?].
AB  - Semen analysis is routinely part of the evaluation of male fertility and includes
      sperm morphology. How sperm morphology can be a diagnostic tool to decide which
      ART to apply for infertile couples (insemination, classical IVF or ICSI)?
      Teratozoospermia has been reported to be one of the most relevant semen
      parameters of clinical interest compared with sperm concentration and sperm
      motility. However, the true potential of this parameter has some limitations
      because of several methodological factors: differences in the classification
      systems, influence of the staining method used, subjective nature of evaluation
      of sperm morphology, regular decreasing of the WHO threshold. According to
      Tygerberg strict criteria that is the most frequently used classification
      worldwide, poor fertilization has been reported when the rate of normal forms was
      less or equal to 4%, suggesting to perform ICSI. However, influence of sperm
      morphology on fertilization outcome remains much debated. Regarding David's
      classification, the threshold of 30% does seem helpful to discriminate in the
      prediction of fertilization success and should probably be reconsidered.

PMID- 20692864
TI  - Acoustic and temporal analysis of speech: A potential biomarker for
      schizophrenia.
AB  - Currently, there are no established objective biomarkers for the diagnosis or
      monitoring of schizophrenia. It has been previously reported that there are
      notable qualitative differences in the speech of schizophrenics. The objective of
      this study was to determine whether a quantitative acoustic and temporal analysis
      of speech may be a potential biomarker for schizophrenia. In this study, 39
      schizophrenic patients and 18 controls were digitally recorded reading aloud an
      emotionally neutral text passage from a children's story. Temporal, energy and
      vocal pitch features were automatically extracted from the recordings. A
      classifier based on linear discriminant analysis was employed to differentiate
      between controls and schizophrenic subjects. Processing the recordings with the
      algorithm developed demonstrated that it is possible to differentiate
      schizophrenic patients and controls with a classification accuracy of 79.4%
      (specificity=83.6%, sensitivity=75.2%) based on speech pause related parameters
      extracted from recordings carried out in standard office (non-studio)
      environments. Acoustic and temporal analysis of speech may represent a potential
      tool for the objective analysis in schizophrenia.

PMID- 20692865
TI  - Delayed-onset oromandibular dystonia after a cerebellar hemorrhagic stroke.

PMID- 20692866
TI  - Polymer complexes: XLXII-interplay of coordination pi-pi stacking and hydrogen
      bonding in supramolecular assembly of [sulpha drug derivatives-N,S:N,O]
      complexes.
AB  - A novel series of nickel(II) polymer complexes of 5-sulphadiazineazo-3
      phenylamino-2-thio-4-thiazolidinone (HL1), 5-sulphamethazine-3-phenylamino-2
      thioxo-4-thiazolidinone (HL2), 5-sulphamethoxazole-3-phenylamino-2-thioxo-4
      thiazolidinone (HL3), 5-sulphacetamide-3-phenyl-2-thioxo-4-thiazolidinone (HL4)
      and 5-sulphaguanidine-3-phenylamino-2-thioxo-4-thiazolidinone (HL5) were prepared
      and characterized. IR spectra show that HL(n) (n=1-5) is coordinated to the metal
      ion in a neutral tetradentate manner with NSNO donor sites of NH (hydrazone's),
      NH (3-phenylamine), carbonyl group and Ph-NH. The title [Ni3(HL(n))2(MU
      OAc)2(OAc)4](n) consists of three Ni(II) atoms linked by interchain pi-pi
      interaction are observed between aromatic rings of two ligands (HL(n)) which are
      further doubly bridged two adjacent nickel atoms by acetate group. The
      geometrical structures of these complexes are found to be octahedral. The nature
      of bonding and the stereochemistry of the complexes have been deduced from
      elemental analyses, thermal, infrared, 1H NMR, electronic spectra, magnetic
      susceptibility and conductivity measurements. The richness of electronic spectral
      in these complexes is also supporting evidence for the trinuclearity of the
      Ni(II) polymer complexes.

PMID- 20692867
TI  - Preliminary evaluation of hydrocarbon removal power of Caulerpa racemosa in
      seawater by means of infrared and visible spectroscopic measurements.
AB  - In this paper we tested the power of Caulerpa racemosa for removal hydrocarbons
      from seawater. C. racemosa was implanted in two aquariums filled with natural
      seawater having a hydrocarbon content lower than 0.05mg/L which is the detection
      limit of the FTIR spectrophotometric method used for the determination. One
      aquarium was submitted to sequential additions of hydrocarbons (n-esadecane 10,
      20 and 40mg/L, n-docosane 15mg/L) and diesel fuels (20mg/L) while the second one
      remained uncontaminated and used as control. After any addition, hydrocarbon
      content in seawater was determined at regular time intervals (one or two days)
      and when comparable hydrocarbon contents (i.e. lower than 0.05mg/L) were again
      observed, the real removal power of hydrocarbons was verified by several
      spectroscopic measurements performed on algae from both aquariums. Total
      hydrocarbon contents in algae determined by infrared (FTIR) spectroscopy, always
      resulted higher in the polluted aquarium for all the concentrations of added
      pollutants. Further FTIR studies performed on algae showed the presence of marked
      quantitative and structural molecular modifications involving carbohydrates,
      proteins, lipids, nucleic acids and chlorophyll pigments in C. racemosa from the
      aquarium test. In addition, visible (VIS) spectroscopic examination of C.
      racemosa showed a reduction of chlorophyll pigments in the polluted aquarium with
      respect to the control one. At last, FTIR spectra all the algal samples submitted
      to hydrocarbon pollution were re-examined by means of two-dimensional correlation
      analysis, a statistical tool helpful for studying the dynamic evolution of any
      molecular and biological system submitted to an external perturbation producing
      compositional and structural changes. This approach showed differences among the
      molecular modifications caused by any type of hydrocarbon used, modifications
      related reasonably to the molecular dimensions and concentration of the added
      pollutants. All these spectroscopic evidences suggested that the removal power of
      C. racemosa depends on its metabolic activities and not only on a simple
      adsorption process.

PMID- 20692868
TI  - Highly diverse and seasonally dynamic protist community in a pristine peat bog.
AB  - Culture-independent molecular methods based on the amplification, cloning and
      sequencing of small-subunit ribosomal RNA genes (SSU rDNAs) are powerful tools to
      study the diversity of microorganisms. Despite so, the eukaryotic microbial
      diversity of many ecosystems, including peatlands has not yet received much
      attention. We analysed the eukaryotic diversity by molecular surveys in water
      from the centre of a pristineSphagnum-dominated peatland in the Jura Mountains of
      Switzerland during a complete seasonal cycle. The clone libraries constructed
      from five different temporal samplings revealed a high diversity of protists with
      representatives of all major eukaryotic phyla. In addition, four sequence types
      could not be assigned to any known high-level eukaryotic taxon but branched
      together with a rather good statistic support, raising the possibility of a
      novel, deep branching eukaryotic clade. The analysis of seasonal patterns of
      phylotypes showed a clear change in the eukaryotic communities between the warm
      period (late spring and summer) and the cold period (autumn and winter).
      Chrysophytes dominated the samples in the cold period while testate amoebae
      (Arcellinida and Euglyphida) and a few other groups peaked in summer. A few
      phylotypes (such as a cryptomonad and a perkinsid) were abundant at given
      sampling times and then almost disappeared, suggesting bloom-like dynamics.

PMID- 20692869
TI  - Low prevalence of fluoroquinolone resistant strains and resistance precursor
      strains in Streptococcus pneumoniae from patients with community-acquired
      pneumonia despite high fluoroquinolone usage.
AB  - We investigated the usage of fluoroquinolones and the prevalence of
      fluoroquinolone resistant pneumococci and their precursors (first step mutants
      and efflux expressing isolates) in patients with community-acquired pneumonia,
      who were enroled into the German CAPNETZ surveillance study from 2002 to 2006
      before the introduction of the pneumococcal conjugate vaccine (n=5780). Thirty
      eight percent of all outpatients received fluoroquinolones. Moxifloxacin
      accounted for 70%, levofloxacin for 19% and ciprofloxacin for 9% of all
      fluoroquinolone prescriptions. One hundred and sixty-three pneumococcal isolates
      from 556 patients with pneumococcal pneumonia were analyzed for fluoroquinolone
      resistance, efflux phenotype, prevalence of mutations within the quinolone
      resistance determining regions and clonality. None of the isolates exhibited
      fluoroquinolone resistance, 1.2% of the isolates contained a first step mutation
      and 6.7% exhibited an efflux phenotype. There was no clonal relationship among
      these strains at increased risk for fluoroquinolone resistance. The absence of
      fluoroquinolone resistance in the context of high fluoroquinolone usage might be
      explained by the high proportion of third-generation fluoroquinolones with
      enhanced activity against pneumococci.

PMID- 20692870
TI  - Conservative treatment of spontaneous dissection of multiple coronary arteries.
AB  - A young woman who presented with chest pain was shown with CT and selective
      coronary angiography to have spontaneous dissections of her left anterior
      descending and distal right coronary arteries. She was managed with enoxaparin,
      aspirin, clopidogrel and metoprolol: she was well with a normal stress
      echocardiogram fourteen months later. Surgical intervention or angioplasty and
      stent deployment may be avoided in such patients if they are clinically stable.

PMID- 20692871
TI  - Pathological complete response: still a relevant endpoint in rectal cancer?

PMID- 20692872
TI  - Long-term outcome in patients with a pathological complete response after
      chemoradiation for rectal cancer: a pooled analysis of individual patient data.
AB  - BACKGROUND: Locally advanced rectal cancer is usually treated with preoperative
      chemoradiation. After chemoradiation and surgery, 15-27% of the patients have no
      residual viable tumour at pathological examination, a pathological complete
      response (pCR). This study established whether patients with pCR have better long
      term outcome than do those without pCR. METHODS: In PubMed, Medline, and Embase
      we identified 27 articles, based on 17 different datasets, for long-term outcome
      of patients with and without pCR. 14 investigators agreed to provide individual
      patient data. All patients underwent chemoradiation and total mesorectal
      excision. Primary outcome was 5-year disease-free survival. Kaplan-Meier survival
      functions were computed and hazard ratios (HRs) calculated, with the Cox
      proportional hazards model. Subgroup analyses were done to test for effect
      modification by other predicting factors. Interstudy heterogeneity was assessed
      for disease-free survival and overall survival with forest plots and the Q test.
      FINDINGS: 484 of 3105 included patients had a pCR. Median follow-up for all
      patients was 48 months (range 0-277). 5-year crude disease-free survival was
      83.3% (95% CI 78.8-87.0) for patients with pCR (61/419 patients had disease
      recurrence) and 65.6% (63.6-68.0) for those without pCR (747/2263; HR 0.44, 95%
      CI 0.34-0.57; p<0.0001). The Q test and forest plots did not suggest significant
      interstudy variation. The adjusted HR for pCR for failure was 0.54 (95% CI 0.40
      0.73), indicating that patients with pCR had a significantly increased
      probability of disease-free survival. The adjusted HR for disease-free survival
      for administration of adjuvant chemotherapy was 0.91 (95% CI 0.73-1.12). The
      effect of pCR on disease-free survival was not modified by other prognostic
      factors. INTERPRETATION: Patients with pCR after chemoradiation have better long
      term outcome than do those without pCR. pCR might be indicative of a
      prognostically favourable biological tumour profile with less propensity for
      local or distant recurrence and improved survival. FUNDING: None.

PMID- 20692873
TI  - Vaccination with a fusion DNA vaccine encoding hepatitis B surface antigen fused
      to the extracellular domain of CTLA4 enhances HBV-specific immune responses in
      mice: implication of its potential use as a therapeutic vaccine.
AB  - Fusion of specific antigens to extracellular domain of cytotoxic-T-lymphocyte
      associated antigen 4 (CTLA4) represents a promising approach to increase the
      immunogenicity of DNA vaccines. We evaluated this interesting approach for its
      enhancement on HBV-specific immune responses and its antiviral effects in HBV
      transgenic mice. A fusion plasmid encoding the extracellular domain of CTLA4
      linked with HBsAg was constructed. Mice were immunized by this fusion plasmid.
      Vaccination with the CTLA4-fused DNA not only induced much higher level of anti
      HBs antibody, but also increased HBsAg-specific CD8+ response as well as CTL
      response in BALB/c mice. Furthermore, both Th1 and Th2 responses were augmented.
      In HBV transgenic mice, the levels of circulating HBsAg and HBV DNA replication
      were down-regulated by induction of higher anti-HBs antibody and HBsAg-specific
      CD8+ response after vaccination with the fusion plasmid. Thus, the CTLA4-fused
      DNA vaccine led to breakdown of immune tolerance to viral infection in HBV
      transgenic mice, which might be used as a therapeutic vaccine in HBV infection.

PMID- 20692874
TI  - Seizures. Introduction.
AB  - Several observations make it worthwhile to take a closer look at postictal
      events, which are defined as manifestations of seizure-induced reversible
      alterations in neuronal function. The postictal period may adversely affect the
      quality of life, considering the duration and severity of postictal events. The
      postictal period is often longer than the seizure itself. Postictal events such
      as psychosis, confusion, aphasia, and paresis can be incapacitating. On a more
      positive side, the increased seizure threshold seen during the postictal period
      may offer clues for development of more effective seizure treatment. In this
      issue, experts in the field elucidate the postictal period from different
      viewpoints, including the mechanism of the postictal period, its diagnostic
      challenges, and its management.

PMID- 20692875
TI  - Clinical features of the postictal state: correlation with seizure variables.
AB  - The postictal period is defined by changes in behavior, motor function, and
      neuropsychological performance that last until the return to a presumed baseline.
      The postictal period has not received as much attention as the time of seizure
      onset or the seizure itself. It may offer information that could be helpful in
      the definition of the epileptogenic zone and its lateralization. Here we review
      different behavioral, neuropsychological, and EEG phenomena of the postictal
      state and discuss several semiological features of the postictal period with
      respect to patient characteristics, seizure duration, influences of drug
      treatment, and secondary generalization. Further evaluation may reveal
      information that could be helpful particularly with respect to resective epilepsy
      surgery, possibly allowing better localization and lateralization.

PMID- 20692876
TI  - Effect of antiepileptic drugs on the postictal state. A critical overview.
AB  - Although postictal events contribute to seizure severity and thus affect quality
      of life, the effect of antiepileptic drugs (AEDs) on the postictal state is not
      well known. This review assesses the available evidence from randomized
      controlled trials on the effect of AEDs on postictal events. The instruments used
      in AED trials include postictal items of The Liverpool Seizure Severity Scale
      (LSSS) and Seizure Severity Scale (SSQ) and postictal recovery of
      electroencephalography (EEG) background activity. The effect of AEDs on postictal
      components of LSSS, if documented separately or at all, was either too small to
      be clinically significant (for lamotrigine) or not different from that of
      controls (topiramate, valproate). However, lacosamide showed improvement on the
      SSQ over placebo, and levetiracetam was associated with a speedier postictal
      recovery of EEG background activity compared with placebo. Although measuring the
      effect of AEDs on postictal state is of great clinical interest, the limited
      evidence found in this review suggests that further work is needed to evaluate
      current instruments used to assess AED-associated changes in postictal events.

PMID- 20692877
TI  - Definition of the postictal state: when does it start and end?
AB  - The postictal state is the abnormal condition occurring between the end of an
      epileptic seizure and return to baseline condition. Applying this definition
      operationally can be difficult, especially for complex partial seizures, where
      cognitive and sensorimotor impairments merge imperceptibly into the postictal
      state. Many patients are unaware of even having had a seizure.
      Electroencephalography sometimes helps to distinguish ictal from postictal
      periods, but may demonstrate focal slowing both during and after a seizure.
      Epileptiform electroencephalographic changes do not always correspond precisely
      to behavioral changes, especially with scalp recordings. The postictal state ends
      at the interictal state, but this too can be ambiguous. Interictal spikes and
      spike-waves can be associated with cognitive and behavioral impairments,
      suggesting that they may represent fragments of ictal episodes. Except where
      boundaries are clear, it is better to describe a sequence of behaviors and
      electroencephalographic changes, without labeling arbitrary stages as being ictal
      or postictal.

PMID- 20692878
TI  - Four-year weight outcomes of laparoscopic gastric bypass surgery and adjustable
      gastric banding among multiethnic adolescents.
AB  - BACKGROUND: Extreme obesity among U.S. adolescents is a serious problem and has
      disproportionally affected ethnic minorities. Recently, surgical intervention for
      morbid obesity in adolescents has gained increasing support. Little information
      is available on the long-term effectiveness of bariatric surgery among ethnic
      minority adolescents. We have reported the weight and body mass index (BMI)
      results for a large cohort of predominantly Hispanic adolescents who underwent
      bariatric surgery in a private practice setting. METHODS: A retrospective medical
      chart analysis of 78 adolescents (77% Hispanic, 19% non-Hispanic white, 1% non
      Hispanic black, and 3% other; 77% female; 16-19 years old), who had undergone
      gastric bypass or banding surgery from 2002 to 2009, was conducted. All patients
      had met the National Institutes of Health criteria for bariatric surgery.
      Repeated measures mixed linear modeling was used to assess the changes in
      weight/BMI from baseline to 4 years after surgery. RESULTS: Non-Hispanic whites
      had lost 104.81 lb and 17.29 BMI units at 1 year after surgery (P <.001 for
      both). Hispanics had lost 91.55 lb and 15.06 BMI units at 1 year after surgery (P
      <.001 for both). The non-Hispanic whites had lost 18.56 BMI units and Hispanics
      16.15 units during the 4 year postoperative period. A weight loss plateau
      occurred at 12 months for the non-Hispanic whites and at 18 months for the
      Hispanics; both groups had maintained their weight loss at 4 years after surgery.
      CONCLUSION: Bariatric surgery resulted in significant weight loss that was
      maintained at 4 years postoperatively among obese ethnic minority adolescents.
      Our results have shown that bariatric surgery is a safe and effective treatment
      option for permanent weight improvements in this demographic.

PMID- 20692880
TI  - Braun's flexor tendons transfer in disabled hands by central nervous system
      lesions.
AB  - INTRODUCTION: Since Braun's article, the nonfunctional hand of brain-injured
      patients has not been the subject of many publications. The objective of surgical
      treatment is to open the hand for hygiene and cosmetic reasons. The technique
      consists in lengthening the extrinsic flexor tendons group. HYPOTHESIS: The
      purpose of this work is to assess eventual functional benefits from superficialis
      to-profundus tendon transfer according to Braun. MATERIAL AND METHODS: Our series
      comprised 15 patients aged a mean 55 years, operated using the Braun procedure
      for a nonfunctional hand (19 hands). Additional procedures were performed as
      required by the local condition (neurotomy of the deep branch of the ulnar nerve,
      wrist fusion, tenotomy of the flexors of the wrist and flexor pollicis longus,
      tenodesis of the extensors of the wrist). The results were assessed by the
      analysis of finger opening ability and by a specific scoring system (Mini Hand
      Score; MHS) rated from 6 (no discomfort) at 20 (major discomfort). RESULTS: The
      mean follow-up was 6 months. We observed imperfect results: thumb opening
      incapacity, spasticity of the intrinsic flexors, and hyperextension of the wrist.
      The preoperative MHS was a mean 13.87 out of 20 and the postoperative MHS was
      9.67 out of 20, with a very substantial difference. DISCUSSION: Our easy-to-use
      system for evaluating the nonfunctional hand (MHS) was shown to be very effective
      in demonstrating the improvement of the postoperative result. The originality of
      our series was to show that Braun's original operation goals were only
      exceptionally and remotely achieved and that an additional technical procedure
      must be nearly systematically considered. All the patients in our series were
      followed up in multidisciplinary team visits where the patient's family and
      caretakers were encouraged to give their point of view. Level of evidence Level
      IV. Retrospective study.

PMID- 20692881
TI  - Shoulder arthroplasty for acute proximal humerus fracture.
AB  - Proximal humerus fracture devascularizing the humeral head may require management
      by prosthesis. Hemiarthroplasty is a logical attitude in such cases, but analysis
      of functional results and complications has identified a certain number of risk
      factors limiting indications. Strict analysis of patient characteristics and of
      fracture type is an essential prerequisite to deciding against treatment by
      immobilization or osteosynthesis. Results in hemiarthroplasty are primarily
      dependent on respecting the rules of the art, which aim at stable anatomic
      osteosynthesis of the surrounding structures so as to restore normal shoulder
      function. The critical steps are the adjustment of implant height and
      retroversion, reduction and fixation of tuberosities and good management of the
      postoperative course. The recent development of fracture-dedicated shoulder
      implants should improve results. In elderly patients, when local conditions are
      unsuitable to hemiarthroplasty, a reverse prosthesis may be used, with an adapted
      surgical technique. Whatever the type of prosthesis, implantation for proximal
      humerus fracture is a demanding operation with definitive impact on the
      functional evolution of the shoulder.

PMID- 20692883
TI  - Effects of hexachlorophene on myelin marker enzymes in rat oligodendrocytes.
AB  - The antibacterial substance hexachlorophene (HCP) can affect myelin formation or
      integrity leading to intramyelinic oedema and vacuolation in the central nervous
      system through an unknown mechanism. These studies were conducted to investigate
      the direct, dose-dependent effects of HCP on myelin membrane markers in cultured
      oligodendrocytes (OLG) isolated from 4-7-day-old rat pups and cultured in vitro
      for up to 5 wk. 2-wk-old OLG cultures were exposed to 0, 0.24 or 0.74 mum HCP for
      48 hr. At 48 hr and again at 5, 12 and 19 days after the end of dosing the myelin
      markers galactosylceramide (GalC), myelin basic protein (MBP), and 2',3'-cyclic
      nucleotide 3'-phosphohydrolase (CNPase) were quantified by ELISA or biochemical
      techniques. DNA was measured to estimate total cell mass and astrocyte
      contamination was determined by an ELISA procedure using anti-glial fibrillary
      acidic protein (GFAP) as the primary antibody. Because of the use of a selective
      culture medium, astrocyte contamination was initially low and continued to
      decrease from wk 2 to 4 as determined by GFAP binding. CNPase, GalC and MBP
      levels were similar in control and low-dose (0.24 mum HCP) cultures with a
      general increase in MBP and CNPase over time. Cultures exposed to 0.74 mum HCP
      showed a decline in GalC proportional to decreased DNA content with time, but
      levels of MBP and CNPase increased after dosing and were always greater than the
      corresponding levels in control or low-dose cultures. These studies suggest a
      direct, dose-related toxic effect of HCP accompanied by a stimulation of MBP and
      CNPase but not of GalC production in the membranes of the recovering OLG
      following removal of HCP.

PMID- 20692884
TI  - Immunomagnetic purification of rat proximal kidney cells.
AB  - A method for producing large quantities of pure proximal tubule cells is
      described. The procedure involves collagenase perfusion to prepare kidney cells
      that are separated by centrifugal elutriation to produce a purified cell
      preparation of proximal tubule cells (PCS). The elutriation-purified cells were
      treated with a rabbit polyclonal antibody to rat gamma-glutamyl transpeptidase
      (GGT). The resulting antibody-labelled cells were then incubated with Dynabeads
      coated with a sheep anti-rabbit IgG antibody. The Dynabeads, which are
      monodispersed polystyrene beads with a magnetic ferrite core, bind specifically
      to the antibody-labelled cells. The cell-bead complexes were then harvested with
      a magnet and washed twice to remove cells not labelled with antibody. The
      procedure is simple and rapid, and can be used to produce 20-25 x 10(6) cells.
      The cells exhibit a well defined brush border membrane with increased GGT and
      alkaline phosphatase enzyme activities. Concomitant with this is a four-fold
      decrease in hexokinase activity, which demonstrates that contaminating distal and
      loop of Henle tubule cells have been removed.

PMID- 20692885
TI  - A quantitative structure-activity relationship (QSAR) investigation of a Draize
      eye irritation database.
AB  - National and international regulations require that the ocular safety of new
      chemicals is established and demand that, unless the substance can be predicted
      to be harmful to the eye, this will be established by means of the Draize rabbit
      eye test. To date, no alternative in vitro methods are accepted by the regulatory
      authorities. Investigation of correlations between physicochemical properties of
      a chemical and its eye irritation potential has received scant attention. A 'gold
      standard' dataset of eye irritation tests collated by the European Centre for
      Ecotoxicology and Toxicology of Chemicals has been supplemented by other
      published data to form a consistent set of biological activities for QSAR
      modelling. Using this dataset, the applicability of QSAR methods for modelling
      the eye irritation responses has been assessed. The possibilities, but also clear
      limitations, of a QSAR approach to the evaluation of eye irritation potential
      have been demonstrated. The dataset is the best available, but nevertheless
      presents several problems: the number of irritants is small compared with the
      number of non-irritants and the whole dataset is chemically heterogeneous, with
      the implication that multiple mechanisms of eye irritation may be involved; the
      data come from several laboratories; the numerical Draize score is a pseudo
      quantitative parameter based on a summation of manipulated subjected scores. A
      molar adjusted eye irritation score proved to be at least partially useful in
      demonstrating and understanding the structure-activity relationships involved
      with such an endpoint. A more promising approach proved to be pattern recognition
      techniques using principal component analysis and relying on the overall
      classification of eye irritation potential. This has led to a qualitative and,
      importantly, testable, relationship between eye irritation potential and
      physicochemical properties, particularly those describing hydrophobicity. The
      availability of quality eye irritation data on more chemicals would allow
      refinement and further testing of this hypothesis.

PMID- 20692886
TI  - Relative importance of oxidation and Ca(2+) in DNA strand breakage by H(2)O(2) in
      the 2sFou cell line.
AB  - The rat hepatoma cell line (2sFou) was used to assess the mechanism of DNA strand
      breakage using the model oxidant H(2)O(2). Exposure of the cells to H(2)O(2) (100
      mum) at 37 degrees C significantly reduced the amount of double-stranded DNA
      remaining after alkaline unwinding at 15 degrees C (control = 75.0 +/- 7.3%, n =
      9, 100 mum H(2)O(2) = 46.5 +/- 8.0, n = 8, P < 0.02). The catalase inhibitor 3
      amino-1,2,4-triazole halved the concentration of H(2)O(2) needed to give a
      significant level of strand breakage (control = 58.6 +/- 3.9%, n = 8, 50 mum
      H(2)O(2) = 36.5 +/- 2.1, n = 3, P < 0.02). The calcium chelator Quin-2 and the
      endonuclease inhibitor aurintricarboxylic acid both inhibited DNA strand breakage
      following treatment with 100 mum H(2)O(2) by 92% and 94%, respectively, whereas
      the lipid peroxidation inhibitor N, N-diphenyl-1,2,4-phenylene-diamine had no
      effect on H(2)O(2)-induced strand breakage. Analysis of the 2sFou cellular DNA
      for the 8-oxodG adduct following H(2)O(2) exposure provided no evidence for
      direct attack of the DNA mediated by hydroxyl radicals. Ca(2+) appears to be the
      major mediator of H(2)O(2)-induced DNA strand breakage.

PMID- 20692887
TI  - Cytotoxic quantification of maitotoxin-like activity from the dinoflagellate
      Gambierdiscus toxicus.
AB  - Gambierdiscus toxicus is a marine dinoflagellate involved in the food-borne
      disease ciguatera. Its toxicity is mainly due to maitotoxin, a hydrophilic toxin,
      the chemical structure of which has recently been described. This toxin increases
      internal Ca(2+) concentration and triggers phosphoinositide breakdown. Three
      cytotoxic tests were set for the detection and quantification of toxicity in G.
      toxicus extracts, further purified by HPLC: the neutral red uptake assay (NRU),
      observation of morphological alterations on baby hamster kidney fibroblasts (BHK
      21/C13) and the measurement of internal Ca(2+) concentration on human lymphocytes
      (Jurkat D). In order to evaluate cytotoxicity tests, results were compared with
      the mouse bioassay. A positive correlation was observed between the minimum
      lethal dose (MLD), estimated at 24 hr by the mouse bioassay, and the IC(50),
      estimated by the NRU assay, for extracts of increasing degree of purity. By the
      use of the NRU assay, a precise detection and quantification of toxicity in
      multiple extracts was possible after 8 hr. Cell blebbing was generally highest
      for extracts that strongly inhibited NRU. The analysis of the correlation between
      the two cytological tests facilitates monitoring of the progression of
      purification. An indication of the presence of maitotoxin activity was supported
      by the increase of internal Ca(2+) concentration in Jurkat D lymphocytes, which
      was maximal in cells exposed to the purest extracts.

PMID- 20692888
TI  - Acute cytotoxicity of ten chemicals in human and rat cultured hepatocytes and in
      cell lines: Correlation between in vitro data and human lethal concentrations.
AB  - The cytotoxicity of ten chemicals from the MEIC list (nos 11-20) was evaluated in
      human and rat cultured hepatocytes and in two established cell lines (HepG2 and
      3T3) according to the Multicentre Evaluation of In Vitro Cytotoxicity programme
      organized by the Scandinavian Society of Cell Toxicology. The lactate
      dehydrogenase intracellular activity and the MTT test were used as endpoints of
      cytotoxicity after 24 hr of exposure to the chemicals. Sodium chloride and
      lithium sulphate were the least cytotoxic compounds in all of the cellular
      systems (IC(50), 25-150 mm). The eight remaining chemicals (1,1,1
      trichloroethane, phenol, sodium fluoride, malathion, 2,4-dichlorophenoxyacetic
      acid, xylene, nicotine and potassium cyanide) showed a similar cytotoxic
      potential in the four in vitro systems in a narrow range of concentrations
      (IC(50), 1-30 mm). The data suggest that these ten chemicals have a basal
      cytotoxic effect common to the four in vitro systems, and probably none of these
      compounds could be considered either hepatotoxic or to exert species-specific
      toxicity. The correlation between in vitro data and human lethal blood
      concentrations showed a relatively low predictability for the toxicity of six
      compounds with important lethal effects on the CNS. The predictability of the in
      vitro systems was similar to that of in vivo rodent tests (LD(50)) only when low
      cytotoxic concentrations (IC(10)) were used for the correlation.

PMID- 20692889
TI  - Comparative cytotoxicity of non-steroidal anti-inflammatory drugs in primary
      cultures of rat hepatocytes.
AB  - The cytotoxicities of 12 non-steroidal anti-inflammatory drugs (NSAIDs) in
      primary monolayer cultures of rat hepatocytes were compared. Toxicity was
      determined by measuring the release of lactate dehydrogenase into the culture
      medium after 20 hr of exposure. Diflunisal was the most cytotoxic, followed, in
      order, by mefenamic acid, diclofenac, indomethacin, flurbiprofen, piroxicam,
      sulindac and ibuprofen. Ketoprofen, naproxen, tolmetin and acetylsalicylic acid
      (ASA) were the least cytotoxic. Phenobarbital pretreatment in vivo potentiated
      the in vitro toxicity of diclofenac, ketoprofen and piroxicam, and SKF525-A
      addition to the medium reduced their toxicity. These results indicate that the
      cytocidal hepatotoxicity of diclofenac, ketoprofen and piroxicam may be mediated,
      at least partially, by cytochrome P-450 metabolism. The cytotoxicity of the other
      nine NSAIDs appears not to be significantly influenced by cytochrome P450
      modulation.

PMID- 20692890
TI  - Development of an in vitro cell culture model to investigate the induction and
      quantification of oxidative stress and its inhibition by alpha-tocopherol.
AB  - The ability of the natural antioxidant alpha-tocopherol to protect against
      oxidative stress in vitro was assessed. Primary cultures of chicken embryo
      fibroblasts (CEF) were oxidatively stressed by exposure to paraquat (PQ).
      Activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT)
      and glutathione peroxidase (GSH-Px) were measured as indices of oxidative stress.
      CEF incubated with 0.125-1.0 mm PQ for 18 hr exhibited increased SOD activity (P
      < 0.05). CAT activity increased with 0.25 mm PQ (P < 0.05). GSH-Px activity
      decreased significantly in the presence of PQ. No cytotoxicity, as indicated by
      lactate dehydrogenase release, was observed at PQ concentrations below 2 mm.
      Incorporation of added alpha-tocopherol (100 nm) into 0.25 mm PQ-treated CEF
      resulted in SOD activity not significantly different from that observed in
      control cells not treated with PQ. Lower levels of added alpha-tocopherol (16 nm)
      returned CAT to its control value. However, even at 1000 nm alpha-tocopherol, GSH
      Px activity was not protected in PQ-treated cells. CEF represent a useful model
      to study both inducers and inhibitors of oxidative stress.

PMID- 20692891
TI  - Use of an in vitro test battery as a prescreen in the assessment of ocular
      irritancy.
AB  - The current OECD guideline for the assessment of eye irritation recommends, in
      initial considerations, the use of data from skin irritation tests as a prescreen
      to detect the most severely irritating materials, assuming that materials that
      are severely irritating to the skin are also significantly irritating to the
      eyes. However, analysis of data for 179 materials tested in this laboratory for
      both dermal and ocular irritancy, revealed that, at most, only 36% of severe eye
      irritants were also severe skin irritants. This resulted in a significant number
      of rabbits developing severe ocular effects that had not been predicted from the
      dermal responses. This study reports the results of an alternative approach for
      predicting severe eye irritants. The approach was a two-stage test battery in
      vitro: the first stage was a cytotoxicity assay utilizing the K562 cell line; the
      second was the isolated rabbit eye test. In contrast to the use of skin
      irritation tests, the in vitro battery was significantly more predictive (83% of
      severe eye irritants were detected). Although the incidence of false positive
      responses in each of the assays precludes their routine use as a replacement from
      the in vivo rabbit eye test they provide a powerful aid to reducing animal use
      and guiding in vivo studies to minimize the severity of effects. The need for an
      interlaboratory assessment to confirm and extend these findings is discussed.

PMID- 20692892
TI  - Organotypic cultures of chick dorsal root ganglia in a semi-solid medium: A model
      for neurotoxicity testing.
AB  - Organotypic cultures of dorsal root ganglia (DRGs) were isolated from 12-day-old
      chick embryos and cultured in a semi-solid medium for use as a model for
      toxicological studies. The mean radial length of neuritic processes growing out
      from the ganglia, the daily rate of neurite elongation, and the area of neurite
      outgrowth were used as parameters to evaluate the toxic influence of three drugs
      (cisplatin, taxol and chlorpromazine) that have neurotoxic side-effects through
      different modes of action on the peripheral nervous system. A significant, dose
      dependent decrease of all parameters of neurite outgrowth was observed in
      cultures treated with different concentrations of the chemicals tested. We
      conclude that the culture system described here may be a useful in vitro method
      to test target organ toxicity in the peripheral nervous system.

PMID- 20692893
TI  - The predominant role of surfactants in the modulation of toxicity of detergent
      products: An in vitro analysis of shampoos.
AB  - 20 shampoos and their component surfactants were studied in vitro using a murine
      epidermal cell line (HEL/30). Lactate dehydrogenase (LDH) leakage into the cell
      medium and the inhibition of protein neosynthesis were evaluated as markers of
      cytotoxicity after 2 hr of exposure. The coefficients of correlation were -0.83
      and -0.69 for comparisons between total surfactant content and inhibition of
      protein synthesis and leakage of LDH, respectively. There was an inverse
      relationship between the inhibition of protein synthesis and the amphoteric
      surfactant content of the shampoo. An excellent correlation (r = 0.94) was found
      between LDH leakage values and scores from eye irritation tests in vivo on seven
      of the shampoos. The results obtained suggest that this model allows quantitative
      evaluation of the cytotoxicity of detergent products (shampoos) and of the
      contribution of their major components (surfactants) to that toxicity.

PMID- 20692894
TI  - Species differences in the time-dependent induction of unscheduled DNA synthesis
      in primary hepatocytes.
AB  - The detectability of quantitative species differences in the in vitro hepatocyte
      DNA repair assay (UDS test) was shown to be strongly dependent on the duration of
      treatment. Primary hepatocytes of rats and Chinese hamsters were treated for 2
      and 18 hr with aflatoxin B(1) (AFB(1)) or 2-acetylaminofluorene (2-AAF). After 18
      hr of treatment with either compound the DNA repair response was much stronger in
      rat hepatocytes than in hamster hepatocytes, whereas after 2 hr of treatment the
      hepatocytes of the two species showed similar responses. Experiments with the
      direct-acting mutagen methylmethane sulfonate indicated that the hepatocytes of
      both species exhibit similar capacities for DNA repair. Since the rates of
      metabolism of AFB(1)- and 2-AAF also did not show significant differences between
      the species, the observed 2 hr/18 hr discrepancy must be attributed to different
      DNA repair kinetics. Further experiments showed that in comparison with rat
      hepatocytes, hamster hepatocytes recovered more rapidly from the isolation
      procedure, but their DNA-repair activity decreased more rapidly during the first
      hours of treatment. Such fundamental differences have to be taken into account
      when comparing the results of UDS tests that have been carried out with
      hepatocytes from different species.

PMID- 20692895
TI  - Effects of cytosine arabinoside on rat and rabbit embryos cultured in vitro.
AB  - The technique of rabbit whole embryo culture for 48 or 24 hr from day 9, 10 or 11
      of gestation has been improved for elucidation of species differences. The
      effects of 1-beta-d-arabinofuranosylcytosine (ara-C) and its metabolite 1-beta-d
      arabinofuranosyluracil (ara-U) on cultured rat and rabbit embryos were examined.
      Slc:SD rats on day 10.5 of gestation were explanted and cultured in rat serum
      containing ara-C (5-10 mug/ml) for 48 hr. Rabbit embryos of the Japanese White
      strain on day 9 or day 10 of gestation were explanted and cultured in rabbit
      serum containing ara-C (0.03-1.0 or 3-30 mug/ml) or ara-U (1.0 or 30 mug/ml) for
      48 or 24 hr. Cultured rat embryos exposed to ara-C showed abnormalities of the
      head (malformations of the telencephalon, mesencephalon and rhombencephalon),
      mandible and limb bud, and short tail. Growth parameters, such as crown-rump
      length, head length, protein content and somite number, were reduced with
      increasing concentrations of ara-C. In the rabbit, embryos cultured from day 9 of
      gestation for 48 hr showed abnormalities of the head (telencephalon,
      rhombencephalon), mandible and limb bud with ara-C at 0.1 mug/ml and higher
      concentrations. Concentration-dependent decreases in crown-rump length, head
      length and protein content were observed. The findings in embryos cultured from
      day 10 of gestation were similar to those in embryos cultured from day 9. Ara-U
      produced no detectable abnormalities in embryos cultured for 48 hr from day 9 of
      gestation, or for 24 hr from day 10. These results indicate that ara-C has
      teratogenicity in vitro that is similar in both rat and rabbit embryos.

PMID- 20692896
TI  - Toxicity to Chinese hamster ovary (CHO) cells of the products of reaction of
      butylated hydroxyanisole with nitrite at low pH.
AB  - Butylated hydroxyanisole (BHA) was found to react readily with nitrite in
      acidified physiological saline. With low concentrations of reactants at pH 2,
      HPLC analysis demonstrated the formation of two products, tert-butylquinone (BQ)
      and a second, unidentified compound. Neutralized BHA/nitrite reaction mixtures
      were highly toxic to cultured Chinese hamster ovary (CHO) cells. At non-lethal
      concentrations, causing some cell cycle delay, there was a statistically
      significant but variable induction of endoreduplication and tetraploidy and a
      very weak induction of chromosome breakage. The effects were similar to those of
      pure BQ. It is suggested that the formation of toxic products from BHA, by an
      oxidative reaction such as that described with nitrite, might be involved in the
      mechanism of BHA carcinogenesis in the rat forestomach.

PMID- 20692897
TI  - Effects of sulfur mustard on selected biochemical parameters of murine peritoneal
      macrophages in culture.
AB  - The effect of the vesicating agent sulfur mustard (SM) has been investigated in
      vitro using murine peritoneal macrophages. The rationale for this study was three
      fold: (1) the first symptoms after exposure to SM are mucous and cutaneous
      erythema, itching and oedema suggesting that inflammatory cells may represent an
      early target of SM toxicity; (2) it has been proposed that macrophages and their
      secretory products may participate in the degradation of the dermal-epidermal
      junction; and (3) macrophages are important components of the immune system and
      any alteration of their metabolism may be relevant in clarifying the immune
      impairments caused by SM. Cell viability, measured by LDH release and lysozyme
      production, was reduced in a concentration-dependent manner following exposure to
      SM at 10 mum or higher. A reduction of superoxide anion and hydrogen peroxide
      production was observed on exposure to concentrations greater than 10 and 1 mum,
      respectively. Cell-associated plasminogen activator activity was significanty
      increased (130% of the control) following exposure to 10 mum and a decrease
      occurred with exposures to 100 mum or more. The release of arachidonic acid
      equivalents was not significantly affected by SM treatment. These results
      demonstrate the cytotoxic effects of SM towards macrophages in culture. While
      activated macrophages may be present in the dermis after in vivo exposure to SM,
      no evidence was found of a direct stimulatory effect of SM on the production of
      macrophage inflammatory products.

PMID- 20692898
TI  - Comparison in human and rat hepatocytes of the DNA-damaging activity of five
      chemicals probably carcinogenic to humans.
AB  - Five chemicals-acrylonitrile, adriamycin, bischloroethyl nitrosourea, phenacetin
      and procarbazine-classified by the International Agency for Research on Cancer as
      probably carcinogenic to humans were assayed for DNA-damaging activity in primary
      cultures of human and rat hepatocytes in order to assess possible interspecies
      differences that might cast doubt on the extrapolation to humans of results
      obtained in rodents. DNA damage was measured by the alkaline elution technique.
      In the range of subtoxic concentrations indicated, dose-related increases in the
      frequencies of DNA single-strand breaks were induced in cells of both species by
      acrylonitrile (1.0-5.6 mm) and procarbazine (5.6-18 mm), whereas phenacetin was
      inactive up to the maximal soluble dose (3.2 mm). Adriamycin (1.8-5.6 mum) and
      bischloroethyl nitrosourea (18-56 mum) produced in cells of both species dose
      dependent increases in the frequencies of both DNA breaks and cross-links. The
      responses of human hepatocytes were qualitatively similar to those of rat
      hepatocytes, but modest statistically significant differences between the two
      species in the average frequencies of DNA lesions were observed with the four
      active agents: the amount of DNA damage was greater in rat than in human
      hepatocytes with acrylonitrile (1.7-fold), adriamycin (1.4-fold), and BCNU (1.3
      fold), whereas procarbazine was more genotoxic (1.4-fold) for human hepatocytes.
      However, as the interindividual variability of the response was greater than that
      occurring between the two species, the results should be interpreted as
      indicating that rat hepatocytes are good predictors of metabolic
      activation/detoxification and DNA-damaging activity in humans for the five
      chemicals studied.

PMID- 20692899
TI  - Acrylonitrile-induced reversible inhibition of uridine uptake by isolated rat
      intestinal epithelial cells.
AB  - Isolated rat intestinal epithelial cells (IEC) were used to investigate the
      mechanism(s) of acrylonitrile (VCN)-induced gastro-intestinal damage. The
      isolated cells were 93% structurally intact for 60 min, as indicated by trypan
      blue exclusion. Uridine uptake by isolated IEC was linear from 6-20 min, after
      which a steady state was reached for up to 40 min. Exposure of isolated IEC to
      various concentrations of VCN reduced the ability of the cells to take up uridine
      in a concentration-dependent manner. A concentration of 82 mum VCN inhibited the
      [(3)H]uridine uptake of the cells by 50% (IU(50)). A time-course study indicated
      that the maximal inhibition of uridine uptake occurred at 15 min after exposure
      to VCN. The VCN-induced inhibition of uridine uptake was found to be reversible.
      IEC exposed to two sublethal doses of VCN (41 and 82 mum) for 15 min regained
      normal uridine uptake activity within 50 min after removal of VCN. The present
      study provides a sensitive approach for the detection and evaluation of cytotoxic
      risk of sublethal doses of the gastro-intestinal toxin VCN using IEC as target
      cells. The observed in vitro cytotoxicity of sublethal doses of VCN will be used
      to investigate further the mechanism of VCN-induced gastro-intestinal damage.

PMID- 20692900
TI  - Biotransformation of carbon tetrachloride in cultured neurons and astrocytes.
AB  - The ability of brain neuronal cells to metabolize carbon tetrachloride (CCl(4))
      has been studied in an attempt to explain earlier observed toxic effects of
      CCl(4) on these cells. The expression of cytochrome P-450, the glutathione (GSH)
      content and the activity of glutathione-S-transferase (GST) were measured in
      cultured neurons and astrocytes from chick embryo cerebral hemispheres. The
      metabolism of CCl(4) in the neuron and astrocyte cultures was also assessed by
      determining the formation of: CCl(2) in membrane preparations of these cells. In
      the membrane fractions of neurons and astrocytes, no measurable levels of
      cytochrome P-450 were observed. Nevertheless, neurons as well as astrocytes had a
      capacity for the metabolism of CCl(4). The metabolic capacity of the neurons was
      significantly greater than that of the astrocytes. The neuron cultures had a
      higher initial content of GSH and a higher control activity of GST than had the
      astrocytes. Neither the GSH level nor GST activity were significantly affected in
      the neuron cultures after exposure to CCl(4). In astrocyte cultures 2 mm CCl(4)
      slightly depleted the GSH level and significantly induced GST activity. At 3 mm
      CCl(4), GSH was depleted by 30% and by more than 50% at 4 mm CCl(4). It can be
      concluded that the metabolic activation of CCl(4) was higher in neurons than in
      astrocytes. This can explain the earlier observation of CCl(4)-induced lipid
      peroxidation in cultured neurons. Moreover, neuron GSH was not able to protect
      these cells against CCl(4)-induced peroxidative damage. In the astrocytes, on the
      other hand, GSH and GST appeared to have a role in detoxification of CCl(4).

PMID- 20692901
TI  - Further evaluation of a teratogenicity screen using an intravitelline injection
      technique.
AB  - A blind trial of 31 compounds was conducted in order to evaluate the
      intravitelline injection technique as a predictor of developmental toxicity. Rat
      conceptuses were explanted on day 9 of gestation and cultured until 11.5 days, at
      which time the compounds were injected into the vitelline circulation of the yolk
      sac. The embryos were then cultured for a further 24 hr after which time they
      were assessed on 14 parameters and assigned to one of three categories based on
      predetermined criteria. The results were then compared with the classifications
      previously allocated using data derived from in vitro studies. The compounds were
      examples of non-teratogens, non-cytotoxic teratogens and cytotoxic teratogens. Of
      the 31 compounds, 23 gave the predicted result, three non-teratogens being false
      positives and five teratogens having no effect in this system. The results
      therefore demonstrate the ability of the technique to distinguish between the
      three categories of compound, displaying a specificity of 75%, a sensitivity of
      74% and an overall accuracy of 74.5%. Furthermore, it allowed the differentiation
      of active and inactive analogues of four paired compounds. This method may have
      applications as a teratogenicity screen or in the elucidation of the mechanism of
      action of teratogenic compounds.

PMID- 20692902
TI  - Evaluation of a three-dimensional human dermal model as a predictor of shampoo
      ocular irritation.
AB  - A three-dimensional human tissue model (Skin(2) ZK1100) was used to evaluate 43
      adult and baby shampoos. The ZK1100 model consists of metabolically active
      proliferating human fibroblasts isolated from the dermis of neonatal foreskins
      and seeded onto a nylon mesh. The fibroblasts multiply and produce matrix
      proteins to form a living tissue. MTT reduction (mitochondrial function) was used
      as the cytotoxicity endpoint. The primary components of the adult shampoos are
      alkyl sulfate surfactants, while the baby shampoos contain ethoxylated alkyl
      sulfates and amphoteric surfactants. All shampoos were diluted to five
      concentrations (100, 300, 700, 1000 and 3000 mug/ml) in aqueous cell culture
      media and the tissue exposed for 24 hr. An EC(50) value for each test was
      generated from a dose-response curve. All samples were tested in two or more
      separate experiments, and the EC(50) values were averaged and plotted versus
      their respective 24-hr unwashed Draize eye irritation values (r(2) = 0.81). The
      adult shampoos had Draize values in the moderate irritation category and EC(50)
      values ranging from 220 to 1051 mug/ml, while the baby shampoos had Draize values
      in the minimal irritation category and EC(50) values ranging from 820 to 2285
      mug/ml. These results indicate that the three-dimensional human tissue model can
      be useful in predicting the Draize ocular irritation category for shampoos.

PMID- 20692903
TI  - Isolation of sinusoidal and canalicular liver plasma membranes: Effects of frozen
      storage of human material.
AB  - Sinudoisal and canalicular plasma membranes were prepared from rat and fresh or
      frozen human liver and characterized using plasma membrane marker enzymes. The
      distributions of these enzymes were used as a means of comparison between the
      plasma membrane fractions and homogenates from the rat and fresh and frozen human
      livers. Compared with their homogenate, all the sinusoidal plasma membrane
      preparations were poorly enriched with Na(+)-K(+)-ATPase (2.6-8.4-fold), a
      sinusoidal marker enzyme. Activities of Na(+)-K(+)-ATPase and Mg(2+)-ATPase were
      much greater in rat membranes whereas leucine aminopeptidase and alkaline
      phosphatase activities were much greater in the human membranes. Consideration of
      the extent of enrichment showed that Mg(2+)-ATPase and alkaline phosphatase are
      better markers in rat canalicular plasma membranes and leucine aminopeptidase in
      human membranes from both fresh and frozen tissue. Intracellular organelle marker
      enzymes were not enriched in the plasma membranes, thus indicating no significant
      contamination. Importantly, the relative enrichments of the marker enzymes showed
      no difference between fresh and frozen human liver. Absolute activities of the
      enzymes were decreased, however (except alkaline phosphatase), after frozen
      storage. This work indicates that human liver tissue may be frozen and stored in
      liquid nitrogen before plasma membranes are isolated with no effect on the
      distribution of marker enzymes in the membranes.

PMID- 20692904
TI  - Developmental toxicity of valproic acid assessed in a sequential culture of
      hepatocytes and embryos.
AB  - The absence of maternal metabolism in the whole rodent embryo culture (WEC) may
      partially be considered as a limitation when chemicals are tested for
      teratogenicity. In the present study, the possibility to combine incubation of
      rat hepatocytes and WEC in a sequential way was investigated, and valproic acid
      (VPA) was used as a model compound. Rat hepatocytes were incubated at a density
      of 2 x 10(6) cells/ml in a mixture of Waymouth medium and human and rat serum
      (5:4:1, by vol.). After 4 hr the culture medium was recovered and used to culture
      8.5-day-old mouse embryos for 24 hr. When VPA (1 mm) was added at the beginning
      of embryo culture, the rates of mortality and dysmorphogenesis were 87 and 100%,
      respectively. When VPA was added at the beginning of the incubation of
      hepatocytes, these values were 18 and 78%, respectively. Moreover, the
      differentiation of embryos was less affected when VPA was added at the beginning
      of the hepatocyte culture. The concentration of VPA decreased during the
      incubation of hepatocytes and glucurono-VPA reached 56% at the end of the
      incubation. Five other unconjugated metabolites were also detected. It is
      concluded that addition of an exogenous metabolic activation system to embryo
      culture results in a decrease of the teratogenic potential of VPA.

PMID- 20692905
TI  - Studies on nickel-induced inhibition of fibroblast growth.
AB  - Nickel chloride inhibited the growth of 3T3 mouse fibroblasts in culture within
      72 hr at 100 mum. This cytostatic effect was not accompanied by a loss in cell
      viability as judged by leakage of lactate dehydrogenase into the culture medium.
      In the log phase of growth the inhibitory effect of 500 mum nickel chloride was
      evident within 4 hr of exposure. This was not accompanied by an alteration in
      cellular reduced glutathione content, indicating that oxidative stress was not
      occurring in the cells. Inclusion of 100 nm alpha-tocopherol in the culture
      medium prevented the cytostatic effect of nickel. Pretreatment with 500 mum
      nickel chloride for 72 hr did not alter glutathione reductase of peroxidase
      activities. Nickel has been implicated in the toxic reactions occurring in
      connective tissue following its use in orthopaedic implants. This study shows
      that the metal inhibits cell growth and may thus depress the ingrowth of
      connective tissue in vivo around the site of implant. Furthermore, alpha
      tocopherol (vitamin E) may be valuable in preventing some of the problems arising
      from poorly fitted or loose implants in vivo.

PMID- 20692906
TI  - In vitro toxicity screening using cultured rat skeletal muscle cells. II. Agents
      affecting excitable membranes.
AB  - The screening of chemicals for their potential to interfere with excitable cell
      membranes should be an important element of in vitro testing for acute toxicity.
      The suitability for this purpose of a test system using primary cultured rat
      skeletal muscle cells was evaluated. The test protocol involved the determination
      of the concentration-dependent effects on three endpoints: (1) spontaneous
      contractility, (2) membrane integrity and (3) energy metabolism. The chemicals
      investigated were: NaCl, KCl and CaCl(2); cardiac glycosides (ouabain, digoxin);
      sodium channel toxins (tetrodotoxin, saxitoxin, veratridine, Anemonia sulcata
      toxin II, Bolocera tuediae toxin II); an acetylcholine agonist (carbachol); a
      calcium antagonist (D600) and three membrane-directed insecticides (deltamethrin,
      DDT, lindane). The response pattern of most of these substances-alteration of
      contractility at concentrations that neither affected the energy metabolism nor
      were cytolethal-characterized them as acting either on the excitable membrane or
      on the excitation-contraction coupling and the contractile apparatus. The results
      indicate that the test system is suited to assess chemical effects resulting in:
      (i) changes of resting membrane and threshold potentials, (ii) altered sodium
      channel function, (iii) opening of endplate channels, (iv) blockade of calcium
      channels, and (v) inhibition of Na(+)/K(+)-ATPase.

PMID- 20692907
TI  - Differential detoxification of two thioether conjugates of menadione in confluent
      monolayers of rat renal proximal tubular cells.
AB  - This in vitro study describes proximal tubular toxicity of quinone thioethers
      after incubation of these compounds on either side of a renal proximal tubular
      cell (RPTC) monolayer. These cells were cultured to confluency on porous supports
      of tissue culture inserts, and the apically and basolaterally induced toxicity of
      two thioether conjugates of menadione (2-methyl-1,4-naphthoquinone) was
      investigated. As judged by lactate dehydrogenase (LDH) leakage, the glutathione
      (GSH) conjugate of menadione (MGNQ) was only toxic after basolateral challenge.
      However, after inhibition of gamma-glutamyl transpeptidase by acivicin, MGNQ was
      also toxic after apical challenge. The mercapturic acid of menadione [M(NAC)NQ]
      displayed cytotoxicity both after apical and basolateral challenge. From the
      basolateral side, MGNQ and M(NAC)NQ-induced cytotoxicity could be enhanced by
      inhibition of the organic anion transport system with probenecid. Inhibition of
      beta-lyase did not influence M(NAC)NQ-induced cytotoxicity. In addition,
      inhibition of intracellular N-deacetylation of M(NAC)NQ using paraoxon
      potentiated the observed toxic effect. Thus, it appears that the MGNQ and
      M(NAC)NQ-induced cytotoxicity is the result of extracellular events, presumably
      redox cycling. Putative uptake of the conjugates is likely to be associated with
      detoxification of these compounds.

PMID- 20692908
TI  - Multivariate factorial analysis of data obtained in seven in vitro test systems
      for predicting eye irritancy.
AB  - Seven in vitro test systems used to predict eye irritancy (EYTEX, SIRC
      cytotoxicity, HeLa cytotoxicity, chorioallantoic membrane (CAM), liposome, red
      blood cell and haemoglobin denaturation test system) were applied to 12
      surfactants, and the results were subjected to multivariate analysis to evaluate
      the relative contributions of five factors. These factors were: (1) cellular
      plasma membrane destruction factor, (2) haemoglobin type protein denaturation
      factor, (3) EYTEX-type protein denaturation factor, (4) cytotoxicity factor and
      (5) an unknown (unidentified) factor. The results clarified the basis on which
      the findings of each test system were related to the Draize results. According to
      the analysis, the Draize eye irritation test could be explained by the
      contribution of the protein denaturation factor and cellular plasma membrane
      destruction factor. This provides support for a previous hypothesis that the
      major mechanisms of eye irritation are cellular plasma membrane destruction and
      protein denaturation. The CAM test value showed a higher correlation coefficient
      (0.906) with the Draize score than did the results of any of the other test
      systems; this was due to the fact that these two tests showed similar patterns of
      dependence on the five factors as indicated by the factorial analysis. The
      haemoglobin denaturation test system had the next highest correlation coefficient
      at about 0.75. Furthermore, by using further tests to make up the deficiency of
      the other necessary factors, a desirable battery system could be predicted; for
      example, the combination of the haemoglobin-denaturation and rat red blood cell
      tests would provide a result similar to that of the Draize test. This study
      should contribute to the development of a rational basis for prediction of eye
      irritancy of chemicals using in vitro test systems.

PMID- 20692909
TI  - Effect of age on the in vitro percutaneous absorption of phenols in mice.
AB  - The effect of age on the in vitro dermal absorption of acetamidophenol, phenol,
      cyanophenol and heptyloxyphenol was examined. Skin from pre-clipped male C57BL/6N
      mice of ages 3, 15 and 27 months was mounted in flow-through diffusion cells.
      [(14)C]Phenol and its analogues (4 mug/cm(2)) were applied to the skin (0.32
      cm(2)) in ethanol (5 mul) and absorption was measured under occluded conditions
      for 72 hr. Significant age effects on the disposition of phenol and
      heptyloxyphenol were observed in the penetration of compound into the receptor
      fluid as well as that retained in the skin. The receptor fluid content of these
      two compounds was significantly greater in 27-month-old mice compared with the
      younger animals. In addition, penetration of phenol in 15-month-old mice was
      significantly greater than in 3-month-old mice. However, the differences in
      phenol penetration were small (< 5%). The maximal flux of cyanophenol and phenol
      penetration were affected by age. The maximal flux for cyanophenol was
      significantly lower in 15-month-old mice than in 3- and 27-month-old animals. The
      maximal flux for phenol was significantly greater in 27-month-old mice compared
      with the younger animals. The overall effect of age on the in vitro dermal
      absorption of phenols in C57BL/6N mouse skin appears to be compound dependent.

PMID- 20692910
TI  - An alternative study of the skin irritant effect of an homologous series of
      surfactants.
AB  - An attempt has been made to differentiate between in vivo and in vitro skin
      reactions to a homologous series of surfactants (sodium alkyl sulfate, R-OSO(3)
      Na) and to determine the usefulness of percutaneous absorption in vitro as an
      alternative test system. Sodium alkyl sulfate showed considerable biological
      activity by virtue of its polar head groups. The length of the lipophilic chain
      in the surfactants was an important factor in their overall activity. The
      following in vivo tests were performed: a primary skin irritation test in guinea
      pigs, a primary eye irritation test in rabbits and a closed patch test in humans.
      Peak skin irritation occurred with C(10)-C(16) sodium alkyl sulfate, which had
      lipophilic groups of different alkyl chain lengths. Cell injury was also
      evaluated by the neutral red dye uptake assay in rabbit corneal (RC) cells. C(4)
      and C(6) compounds had no effect, while maximal effects occurred with C(18).
      Protein denaturation and haemolysis occurred with C(10)-C(16) compounds. In the
      percutaneous absorption test in guinea pig skin, permeation was low for the C(18)
      compound and high for the C(4) compound. The results with the C(18) compound
      suggest that differences between cell injury and skin irritation result from skin
      permeation. Although the C(18) compound caused cell injury, membrane destruction
      and protein denaturation were more severely with the C(10)-C(16) compounds, owing
      to their strong haemolytic and protein-denaturation action.

PMID- 20692911
TI  - Free-radical damage by UV or hypoxanthine-xanthine oxidase in cultured human skin
      fibroblasts: Protective effects of two human plasma fractions.
AB  - Two in vitro methods to investigate free radical damage to cultured human skin
      fibroblasts have been used: irradiation with UVA or UVB, producing intracellular
      free radicals and DNA damage, or free radical production by the enzymatic system
      hypoxanthine-xanthine oxidase, releasing free radicals into the culture medium.
      These methods differ not only in the location of the free radicals generated but
      also in their nature and kinetics. The antioxidant properties of two human plasma
      extracts A and B (derived from Cohn's fraction IV and Cohn's fraction I + III)
      were investigated before, during and/or after the oxidative stress. Protection
      was observed when the fractions were added concomitantly with the enzymatic
      system (at 5 g/litre, fractions A and B exhibited, respectively, 77 and 50%
      activity) or during UVB irradiation (37 and 68% activity for fractions A and B,
      respectively at 5 g/litre). A small degree of protection was observed against UVA
      damage. No preventive or restorative effect was observed with the UVB system. The
      two fractions prevented UVA damage (at 2.5 g/litre, fraction A and B elicited 22
      and 23% activity, respectively) but only fraction A also exhibited a restorative
      effect (at 5 g/litre, activity was 26%). One of the protective mechanisms could
      be the enhancement of intracellular antioxidant enzyme activity by incubation of
      cells with fractions A and B (after 24 hr of contact with fraction B, total
      glutathione peroxidase and glutathione peroxidase Se-dependent activities were
      significantly increased by 60 and 42%, respectively, compared with control
      values).

PMID- 20692912
TI  - A simple fluorescence method for the study of the internalization of particles in
      cultured cells: Application to asbestos and glass fibres.
AB  - A model for the study of internalization of particles in mammalian cells was
      applied to asbestos and glass fibres. Briefly, a fluorescent fluid-phase
      endocytic marker, Lucifer Yellow CH (LY), was allowed to be incorporated into the
      lysosomal compartment of Syrian hamster embryo cells. Mineral fibres that were
      internalized by the cells subsequently became 'fluorescent', presumably when the
      fibre-containing endosome fused with the LY-containing lysosomes. This method was
      compared with differential interference contrast (DIC) optics. Approximately
      three times as many of the cell-associated fibres were determined to be
      internalized by the fluorescence method compared with DIC optics. Both fine and
      coarse glass fibres were internalized as effectively as asbestos fibres. The
      relative frequency of internalized (i.e. fluorescent) fibres increased until 4 hr
      after exposure compared with the total number of cell-associated fibres. The
      frequency of internalized fibres compared with the number of cell-associated
      fibres was constant over the range of fibre levels studied. A surface
      modification (octadecyldimethylchlorosilane-derivatization) of amosite fibres
      that decreased the carcinogenicity of the fibres, decreased slightly the number
      of internalized fibres relative to the number of cell-associated fibres, but this
      was not statistically significant. Cytoskeleton-interfering agents significantly
      decreased the relative number of internalized fibres.

PMID- 20692913
TI  - Percutaneous absorption of diethyl phthalate through rat and human skin in vitro.
AB  - The percutaneous absorption of the plasticizer and fragrance chemical diethyl
      phthalate (DEP) has been evaluated in vitro in flow-through diffusion cells using
      shaved full-thickness skin from male Fischer 344 rats and human breast skin. Neat
      DEP (16.3-20.6 mg/cm(2)) was applied to the epidermal surface of the skin, which
      was then either left uncovered (unoccluded) or covered (occluded) with a teflon
      cap 2.9 cm above the skin surface. The absorption of DEP through rat skin and
      into the receptor fluid was relatively extensive reaching 35.9 +/- 2.9% (mean +/-
      SD, n = 4) of the applied dose over 72 hr when the skin was occluded and 38.4 +/-
      2.5% (mean +/- SD, n = 3) when the skin was unoccluded. Absorption of DEP through
      human skin was significantly less (P < 0.05) than through rat skin reaching 3.9
      +/- 1.2% (mean +/- SD, n = 4) of the applied dose over 72 hr when the skin was
      occluded and 4.8 +/- 0.7% (mean +/- SD, n = 3) when the skin was unoccluded.
      Occlusion of the skin did not significantly alter the percutaneous absorption of
      DEP through rat or human skin. There was a four-fold variation in absorption
      between skin samples taken from human donors, ranging from 1.6 +/- 1.2% (mean +/-
      SD, n = 3) to 8.7 +/- 3.9% (mean +/- SD, n = 6) at 72 hr. This inter-individual
      variation was greater than the variation between animals, which ranged from 26.4
      +/- 3.3% (mean +/- SD, n = 4) to 38.9 +/- 0.6% (mean +/- SD, n = 5). This
      information may be of significance for the safety evaluation of DEP for
      occupational and consumer use. Although human in vivo data are lacking, the
      percutaneous absorption of DEP through rat skin in vitro compares well with rat
      in vivo data from the literature, which supports the use of this technique as a
      model for in vivo absorption.

PMID- 20692914
TI  - An in vitro study of the eye irritation potential of new shampoo formulations.
AB  - Several in vitro methods have been used to investigate the toxicity of potential
      eye irritants with a view to replacing in vivo eye irritation testing. Initially,
      a group of surfactant and surfactant-based products, for which in-house in vivo
      Draize eye irritation data were already available, were studied in a range of in
      vitro assays. This approach obviated the need to generate in vivo data
      specifically to evaluate the current in vitro programme. Chinese hamster V79
      cells, mouse peritoneal macrophages, mouse Balb/c 3T3 cells and mouse L929
      fibroblasts were used together with several different endpoints of toxicity,
      including dye retention techniques, reductive capacity and morphological
      assessment. In addition, the samples were tested in a bacterial bioluminescence
      system, Microtox. The data from previous studies indicated that the best
      agreement with irritancy data was obtained using a test battery consisting of
      fluorescein diacetate incorporation by V79 cells, neutral red uptake by 3T3
      cells, the L929 agarose overlay assay and the Microtox assay. This report
      presents an example of the use of this in vitro evaluation process for surfactant
      based personal products. In each case, the in vitro toxicity of the new
      formulation was compared with that of a range of related products for which
      historical eye irritation data, generated using either the Draize test in vivo or
      the enucleated eye assay in vitro, were available. The data for each in vitro
      assay were evaluated by comparing the toxicity rank order with the available
      historical data. In general, the in vitro ranking was in good agreement with the
      historical data, although the L929 assay proved to be of limited value. This
      approach allowed the completion of the safety evaluation process for the novel
      formulations.

PMID- 20692915
TI  - Glutathione content, glutathione transferase activity and lipid peroxidation in
      acrylamide-treated neuroblastoma N1E 115 cells.
AB  - Acrylamide is a well known neurotoxic compound that produces central and
      peripheral distal axonopathy. Degenerative changes of this type can be induced in
      the neuroblastoma cell line C 1300, clone N1E 115 and have been extensively
      studied in our laboratory particularly with regard to the interference by
      acrylamide with cellular metabolism. In the present study the mechanism of
      acrylamide-induced neurite degeneration in N1E 115 cells is elucidated further.
      Acrylamide concentrations were selected that were not cytotoxic but caused an
      increasingly severe neurite degeneration. The rate of protein synthesis was
      decreased in a concentration-dependent manner in response to acrylamide exposure
      (0-2.5 mm). Detoxification of acrylamide in vivo occurs mainly through
      conjugation with glutathione, (GSH) both non-enzymatically and enzymatically by
      glutathione S-transferases (GST). Cells grown in the presence of acrylamide
      showed a concentration-dependent decrease in GSH content. At the highest
      acrylamide concentration tested this was accompanied by an increased GST
      activity. Despite the reduced level of GSH and possible impaired protection of
      the plasma membrane against oxidative stress no elevated level of lipid
      peroxidation could be observed in the acrylamide-treated cells.

PMID- 20692916
TI  - Evaluation of cytotoxicity and genotoxicity of okadaic acid, a non-phorbol ester
      type tumour promoter, in V79 Chinese hamster lung cells.
AB  - Okadaic acid, a specific phosphatase inhibitor and non-phorbol ester type tumour
      promoter, was examined for cytotoxic and genotoxic properties in a hepatocyte
      mediated assay with V79 Chinese hamster lung fibroblasts. Genetic endpoints
      measured were: mutation to 6-thioguanine resistance at the hgprt gene locus and
      induction of sister chromatid exchange (SCE). The cytotoxicity of okadaic acid to
      V79 cells was determined in the absence of hepatocytes at concentrations from 0
      to 30 ng/ml medium. Okadaic acid decreased colony size at 20 ng/ml, reduced
      colony formation by 50% (LC(50)) at 24 ng/ml, and was lethal to 100% of the cells
      at concentrations above 30 ng/ml. Exposure of V79 cells to okadaic acid for as
      little as 24 hr without hepatocytes invoked morphological changes that were
      concentration related. By comparison, okadaic acid was less able to invoke
      changes in morphology of V79 cells when co-cultivated with rat hepatocytes, but
      did alter hepatocyte morphology. In genotoxicity tests, mutation frequencies were
      increased signficantly by okadaic acid only in the absence of hepatocytes and
      only at the highest tested concentration (20 ng/ml medium). In contrast, SCE
      frequencies were not affected when okadaic acid was tested alone or with
      hepatocyte activation at concentrations as high as 20 ng/ml. It was concluded
      that, within the limits of the test system used, okadaic acid was strongly
      cytotoxic and may function as a direct-acting mutagen, but was otherwise without
      cytogenetic activity towards V79 cells.

PMID- 20692917
TI  - Deoxyuridine suppression test on isolated rat bone marrow cells and the in vitro
      effect of bidisomide.
AB  - The deoxyuridine suppression test was performed on isolated rat bone marrow cells
      in order to study the effect of bidisomide, a new Class I antiarrhythmic agent,
      on folate-dependent DNA synthesis. Methotrexate and 5-fluorouracil, two known
      inhibitors of DNA synthesis, were included in the study to validate the test
      system. Methotrexate and 5-fluorouracil, at a concentration of 5.5 mum, decreased
      thymidine incorporation into DNA by way of the de novo pathway (thymidylate
      synthase activity). The salvage pathway of DNA synthesis (thymidine kinase
      activity), however, was not affected by these anticancer drugs. Bidisomide up to
      1 mm did not affect the folate-dependent thymidylate synthase activity, nor the
      thymidine kinase activity of isolated rat bone marrow cells.

PMID- 20692918
TI  - Episkin, a reconstituted human epidermis for assessing in vitro the irritancy of
      topically applied compounds.
AB  - The Episkin epidermal system is a reconstituted organotypic culture of human
      keratinocytes forming a multilayer differentiated epidermis on a collagen matrix.
      This standardized model was used to measure various parameters reflecting
      irritation observed in vivo following topical application of a variety of
      surfactants. A comparison of the results with historical data from ocular
      irritation testing in vivo showed a strong correlation for cytotoxic potential (r
      = 0.93; n = 23; P < 0.00001) and damage to the epithelial barrier function (r =
      0.87; n = 20; P < 0.00001). In addition, the proportion of agents for which the
      irritative potential is underestimated is low. With regard to cutaneous
      irritation, the release of a major pro-inflammatory cytokine, interleukin 1alpha,
      correlated with the degree of irritation observed in vivo (r = 0.81; n = 20; P <
      0.0001). Given its suitability to testing a wide variety of parameters reflecting
      irritation and the fact that all types of topical formulations can be applied to
      the reconstructed epidermal surface, the Episkin model should be particularly
      useful for assessing the tolerability of topical agents in vitro.

PMID- 20692919
TI  - Urea production in long-term cultures of adult rat hepatocytes.
AB  - To study the functionality of the urea cycle in long-term cultures of adult rat
      hepatocytes, urea production and the activity of two urea cycle enzymes were
      measured in hepatocytes cultured on 3T3 cells for 15 days. Urea production was
      also measured in cultures maintained with medium containing either 0.4 mm
      arginine or 0.4 mm ornithine and in cultures exposed to different concentrations
      of NH(4)Cl, an in vivo inducer of urea production. In hepatocytes seeded on 3T3
      cells, urea production decreased gradually to 50% of the initial value after 15
      days. Urea production was similar in 3T3-hepatocyte cultures maintained for 11
      days with medium containing ornithine or arginine. Hepatocytes exposed for 24 hr
      to 1, 3 and 5 mm NH(4)Cl showed an average increase in urea production of 25, 50
      and 69%, respectively, above that of unexposed cultures over 15 days. Ornithine
      transcarbamylase (OTC) activity decreased by 84% after 5 days in culture and
      remained constant thereafter, while arginase activity remained constant over 15
      days. In contrast, in hepatocytes seeded on plastic substratum, urea production
      decreased to 24% of the initial value after 8 days in culture. OTC and arginase
      activities also decreased to 13 and 10% of their initial values after 8 days in
      culture. These results show that 3T3-hepatocyte cultures from adult rats produce
      urea from ornithine and/or arginine for at least 15 days and respond to an
      inducer of urea production as in vivo. They also show that these cultures have
      decreasing and constant levels of OTC and arginase activities, respectively,
      owing probably to an adaptative response dependent on substrate concentrations
      and hormonal regulation. These findings also suggest that 3T3-hepatocyte cultures
      are a suitable in vitro system to study urea production, its regulation by
      substrates and hormones and its alteration by drugs and toxic chemicals.

PMID- 20692920
TI  - In vitro transformation potential of N-polycyclic aromatic hydrocarbons in rat
      tracheal epithelial cells.
AB  - Nitro-polycyclic aromatic hydrocarbons (nitro-PAHs) are environmental
      contaminants and potential human airway carcinogens. Agents of this class show a
      wide range of potencies for toxicity, mutagenicity and carcinogenicity that are
      associated with the structure of the PAH and the position of the nitro group. In
      order to evaluate the effect of nitro substitution on in vitro biological
      activity, the cytotoxicity and transformation potential of two parent PAHs,
      pyrene and chrysene, and a series of nitro derivatives were examined in the rat
      tracheal epithelial (RTE) cell system. The nitro derivatives, but not pyrene or
      chrysene, produced dose-dependent decreases in the colony forming efficiency of
      the RTE cells. The most cytotoxic agents were 1,6-dinitropyrene and 6
      nitrochrysene with ED(50)s of 1.6 mum and 5.9 mum, respectively, followed by 4
      nitropyrene and 1-nitropyrene with ED(50)s of 26.3 mum and 44.5 mum,
      respectively. These compounds were evaluated for transformation potential at
      three treatment levels that spanned the cytotoxic range, and the assays were
      scored for morphologically transformed preneoplastic colonies. The control or
      spontaneous transformation frequency in this series of experiments was 1.79 +/-
      0.47 (x 10(-4)). 6-Nitrochrysene and 1,6-dinitropyrene were the only compounds
      that produced transformation frequencies (12.17 x 10(-4) and 9.68 x 10(-4),
      respectively) that were statistically different from control. The maximum
      transformation frequencies of the compounds were compared with published data for
      liver tumorigenicity in the newborn mouse assay. The orders for tumorigenicity
      and transformation were the same (1,6-dinitropyrene > 4-nitropyrene > 1
      nitropyrene approximately - pyrene and 6-nitrochrysene > chrysene), and the
      relative potencies of the compounds were similar in the two assays. These results
      suggest that RTE cells are capable of metabolizing nitro-PAHs to reactive
      products, and that, within this limited class of compounds, in vitro
      transformation data in the RTE cell system may be correlated with tumorigenicity
      in animal studies.

PMID- 20692921
TI  - Modulation of thyroxine uptake and efflux in vitro by temelastine and
      phenobarbital in cultured hepatocytes from different species, in relation to
      toxicological effects on the thyroid gland.
AB  - Toxicological studies in the rat with phenobarbital and temelastine (SK&F 93944)
      are associated with thyroid lesions, characterized by thyroid stimulated hormone
      mediated thyroid follicular cell hypertrophy and hyperplasia. It has previously
      been demonstrated that these compounds enhance the hepatocellular accumulation
      and clearance of thyroxine (T(4)), in rat but not dog or mouse. In this study
      these events were further characterized in vitro using cultured hepatocytes from
      different species. Exposure of rat hepatocytes in vitro to phenobarbital and
      temelastine produced significant increases (P < 0.05) in hepatocellular [(125)I]l
      thyroxine accumulation, following 3 hr of exposure to either drug (at a
      concentration of 10 mum), in the presence of [(125)I]T(4) (0.107 nm final
      concentration). At this concentration the accumulation of [(125)I]T(4) after
      xenobiotic exposure was 132.6 +/- 1.5% (phenobarbital) and 135 +/- 2.0%
      (temelastine) of control values. There was no apparent xenobiotic-induced
      cytotoxicity (as determined by the mitochondrial MTT index) up to 20 mum
      temelastine and 50 mum phenobarbital in rat hepatocytes. Experiments performed at
      4 degrees C [or under conditions of cellular ATP depletion, induced by 1 mum
      carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone (FCCP) treatment] failed to
      show any such increase in hepatocellular thyroxine accumulation. Pretreatment of
      hepatocytes with either phenobarbital or temelastine for 3 hr before the addition
      of radiolabelled thyroxine produced increases in hepatocellular hormone
      accumulation similar to those observed when [(125)I]T(4) and drug were added to
      the cultures simultaneously. The earliest time at which any increase in
      [(125)I]T(4) accumulation was observed after drug exposure was approximately 90
      min. Exposure of hepatocytes from guinea pig or beagle dog to phenobarbital or
      temelastine in vitro failed to produce similar increases in hepatocellular
      [(125)I]T(4) accumulation, demonstrating species specificity of the xenobiotic
      effect in vitro.

PMID- 20692922
TI  - Effects of aflatoxin B(1) in a liver cell line from rainbow trout (Oncorhynchus
      mykiss).
AB  - The cytotoxic response to aflatoxin B(1) (AFB) was investigated in RTL-W1, a cell
      line derived from the normal liver of a mature rainbow trout (Oncorhynchus
      mykiss). AFB altered RTL-W1 morphology and ultrastructure and inhibited DNA
      synthesis. The effective concentration required for 50% inhibition (EC(50)) of
      DNA synthesis, after 2 days of treatment was 0.04 mug/ml. This response was
      compared with that of two other salmonid, but non-liver, cell lines [rainbow
      trout gonad (RTG-2) and Chinook salmon embryo (CHSE-214)]. Although RTG-2 cells
      were as sensitive as RTL-W1 cells (EC(50) for inhibition of DNA synthesis was
      0.05 mug/ml), CHSE-214 cells were unresponsive to AFB at concentrations as high
      as 2 mug/ml. After a single AFB exposure, RTL-W1 sublines were isolated that had
      phenotypic changes typical of malignant transformation. These were increased
      growth rate, reduced contact inhibition of growth, altered cellular morphology
      and growth in soft agar. In addition, RTL-W1 metabolized AFB: the major
      metabolites, aflatoxin (AFL) and aflatoxin M(1) (AFM), were detected by thin
      layer chromatography and HPLC. The relative amounts of these metabolites, unlike
      those observed with RTG-2 cells, were in close agreement with those produced by
      trout liver in vivo. Thus, RTL-W1 could provide a sensitive in vitro model system
      for studying the action of biotransformation requiring xenobiotics. Overall, the
      observed responses were similar to those reported for liver cells in AFB-exposed
      trout, suggesting that RTL-W1 cells are suitable for studying cytotoxic effects
      and malignant transformation in vitro.

PMID- 20692923
TI  - Toxicity of structurally related anthraquinones and anthrones to mammalian cells
      in vitro.
AB  - Anthraquinones and structurally related compounds were cytotoxic to mammalian
      cell lines using cloning efficiency and MTT reduction as endpoints. In V79 cells,
      the concentration of chemical causing 50% inhibition ranged from 0.21 to 21.6
      mug/ml for cloning efficiency and from 0.86 to 14.6 mug/ml for MTT reduction. The
      anthrones anthralin and chrysarobin were 4.1 and 3.2 times more toxic,
      respectively, in the cloning efficiency assay than in the MTT assay. In contrast,
      the anthraquinones danthron and emodin were 2.8 and 2.1 times more toxic,
      respectively, in the MTT assay than in the cloning efficiency assay. Among the
      four mammalian cell lines tested using the MTT assay, the human leukaemia cell
      line (K562) was the most sensitive to the test chemicals. In contast,
      anthraquinone toxicity was reduced in rat hepatoma (H4IIE) cultures. In general,
      structures with carbonyl groups in positions 9 and 10 on the anthracene skeleton
      (anthraquinones) were less toxic than structures with carbonyl groups in position
      9 only (anthrones). Toxicity was also influenced by the position of hydroxy
      substituents on the tricyclic skeleton. The results suggested that in vitro
      cytotoxicity assays are useful in elucidating the relationships between structure
      and biological activity for anthraquinones and related compounds.

PMID- 20692924
TI  - Spermine toxicity in BHK-21/C13 cells in the presence of bovine serum: The effect
      of aminoguanidine.
AB  - Spermine was toxic to BHK-21/C13 cells in the presence of newborn calf serum and
      the toxicity, but not the metabolism of spermine, was prevented by
      aminoguanidine. Aminoguanidine treatment resulted in significant alterations in
      the polyamine profile of these cells with loss of intracellular putrescine after
      4 hr of exposure. In the presence of aminoguanidine, intracellular polyamine
      content returned to control values at 24 hr, possibly as a result of increased
      uptake of exogenous spermine.

PMID- 20692925
TI  - Adenine and pyridine nucleotide concentrations and relationships to 2,6
      dinitrotoluene metabolism in cultured rat liver slices.
AB  - The relationships between nucleotide (ATP, ADP, AMP, NADPH, NADP(+), NADH and
      NAD(+)) concentrations and the metabolism of the hepatocarcinogen 2,6
      dinitrotoluene (2,6-DNT) in cultured slices of rat liver were investigated. ATP,
      NADPH and NADH concentrations in freshly prepared rat liver slices at the
      beginning of culture were 48-67% lower than those measured in freeze-clamped rat
      liver (in vivo values). ATP concentrations in cultured liver slices increased
      with time of incubation, and after 4 hr ATP concentrations in liver slices were
      25% greater than in vivo values. In contrast, NADPH and NADH concentrations did
      not recover with time of culture, and after 4 hr NADPH and NADH concentrations in
      liver slices were 50 and 24% of in vivo values, respectively. The addition of
      ethanol (50 mm) to cultured liver slices increased NADH concentrations by 132%,
      relative to untreated liver slices. Treatment of liver slices with ammonium
      chloride (10 mm), 6-aminonicotinamide (1 mm), or the substitution of fructose for
      glucose in the incubation medium significantly decreased NADPH concentrations by
      64, 44 and 63%, respectively. All treatments significantly decreased ATP
      concentrations; fructose was the most effective agent tested and decreased liver
      slice ATP concentrations by 69%. These results indicate that the changes in liver
      slice nucleotide concentrations that occur during culture are not irreversible,
      and we suggest that these changes are a homoeostatic response to culture
      conditions and not a reflection of tissue damage or cytotoxicity. Rates of 2,6
      dinitrotoluene metabolism by rat liver slices were unaffected by fructose or
      ammonium chloride, despite the decrease in NADPH concentrations produced by these
      agents. These results suggest that NADPH concentrations are not rate-limiting to
      2,6-DNT metabolism by rat liver slices.

PMID- 20692926
TI  - Alterations in the glial fibrillary acidic protein content of primary astrocyte
      cultures for evaluation of glial cell toxicity.
AB  - Astrocyte-enriched primary glial cell cultures from the rat cerebral cortex were
      exposed to a range of neurotoxic compounds and the effects on three proteins were
      examined by enzyme-linked immunosorbent assay (ELISA). The most consistent marker
      for astrocyte toxicity was the intermediate filament protein glial fibrillary
      acidic protein (GFAp). Many toxicants reported to have specificity for astrocytes
      (e.g. mercuric chloride, aluminium chloride, toluene or ethanol) produced a
      similar dose-response curve: increases in the GFAp content of the cells at sub
      cytotoxic concentrations with attenuation at higher concentrations. Some of the
      concentrations required to increase GFAp were extremely low, indicating that this
      is a sensitive and consistent marker of cellular damage, as has been shown in
      vivo. Toxicants that have neuronal specificity (such as 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridinium or acrylamide) had no effects on GFAp levels, indicating
      that the system measures the susceptibility of astrocytes to specific toxicants
      rather than neurotoxicity. The levels of S-100 protein and vimentin were measured
      for a smaller number of toxicants. S100 was a less sensitive and inconsistent
      marker in comparison with GFAp, whilst vimentin levels were not seen to increase
      with any tested compound. These results suggest that astrocytes have a valuable
      place in culture models for neurotoxicity testing.

PMID- 20692927
TI  - Interleukin-1 production after treatment with non-ionic surfactants in a murine
      keratinocytes cell line.
AB  - Detergents are well known irritating agents in human as well as in animal models.
      Using a murine keratinocyte cell line (HEL30) changes in the interleukin-1alpha
      profile were characterized in response to three non-ionic detergents, all widely
      used in the cosmetics industry. The compounds used in this study were the most
      active (dodoxynol-9, Delta-9), moderate (polyglyceryl-4-lauryl ether, PEL) and
      mild (PEG-20-glyceryl ricinoleate + ricinoleamide DEA, PEG) in inducing
      cytotoxicity, measured as lactate dehydrogenase leakage and de novo protein
      synthesis, on the same cell line after 2 hr of treatment. All of the surfactants
      tested were able to induce IL-1alpha production both at a secretory and cell
      associated level. However, in order to achieve a similar IL-1 production
      different concentrations of surfactants were necessary. It was possible to
      calculate an EC(50) for IL-1alpha release of 52.9 mug/ml for Delta-9, of 293.7
      mug/ml for PEL and of greater than 9000 mug/ml for PEG. At the concentration of
      30 mug/ml no release could be detected even after 24 hr of treatment with PEL or
      PEG. A time-course experiment also showed significant amounts of IL-1alpha 20 min
      after treatment with Delta-9. These data confirmed Delta-9 as the most potent of
      the three non-ionic detergents tested in inducing IL-1alpha release. The
      surfactants were also tested in vivo using the modified Draize test. Once again
      Delta-9 was the most active, followed by PEL and PEG. Considering the key role of
      IL-1 in the inflammatory response, the release of this cytokine by keratinocytes
      in vitro could be used as a more specific (in comparison with classical cytotoxic
      markers) and early marker to determine the irritant potential of water-soluble
      chemicals.

PMID- 20692928
TI  - Comparative toxicity of valproic acid and its metabolites in liver slices from
      adult rats, weanling rats and humans.
AB  - The incidence of fatal hepatic failure associated with valproic acid (VPA)
      treatment is low but when it occurs, 90% of the affected patients are below the
      age of 20 yr. At present the mechanism of VPA hepatotoxicity is unclear; however,
      it may be a combination of the formation and action of toxic metabolites in
      developing tissues. In the study reported here we investigated the action of VPA
      and its metabolites in liver slices prepared from adult and weanling Sprague
      Dawley rats and from human livers (non-transplantable livers from organ donors,
      or biopsy material from patients undergoing surgical liver resection). VPA, 2
      propyl-2-pentenoic acid (2-en-VPA or Delta(2)-VPA), 2-propyl-4-pentenoic acid (4
      en-VPA or Delta(4)-VPA) were incubated for various times at concentrations of 100
      or 300 mug/ml. Protein synthesis and K(|) content were used to assess functional
      integrity or general viability. The question addressed was whether there were
      differences in the in vitro toxicity of VPA and its metabolites that were related
      to the age of the livers from which the slices were taken. Liver slices from
      weanling rats were significantly more sensitive to VPA and its metabolites than
      the slices from livers of adult rats. The rank order of toxicities (4-en-VPA >
      VPA > 2-en-VPA) was the same in both sets of rat slices. The human liver slices
      were significantly affected by VPA and its metabolites but these compounds were
      equal in their ability to produce this toxicity. There was also an indication of
      differences in sensitivity to the toxicity of VPA in slices from livers of donors
      of different ages.

PMID- 20692929
TI  - Interlaboratory assessment of the bovine corneal opacity and permeability (BCOP)
      assay.
AB  - A multinational interlaboratory study to investigate the bovine corneal opacity
      and permeability (BCOP) assay is presented. The aim of this work was to determine
      the capability and possible limitations of this method to predict ocular
      irritancy of a large set of chemicals. The assays were carried out in 12 European
      laboratories with different types of activity. In each of these laboratories 52
      substances, with a wide range of structure, physical form and irritant
      properties, were tested and in vitro scores were compared with those obtained
      from concurrent rabbit eye (Draize) tests. The technique was easily learned by
      workers in the participating laboratories, as shown by the fact that there were
      consistent responses between treated corneas within an individual laboratory.
      Interlaboratory variability was also very good. It was found that a given
      laboratory had a 96% chance of classifying irritants or non-irritants similarly
      to the other laboratories. In addition, it was observed that corneas preserved
      overnight responded similarly to freshly prepared tissues, thus allowing
      flexibility for those laboratories where the availability of corneas is limited.
      Comparisons between in vivo and in vitro data showed that the BCOP data correctly
      predicted whether a compound would be irritating or non-irritating for 44 of the
      52 compounds (84.6%). Specificity and sensitivity were also greater than 84%, and
      the same number of substances were overestimated as were underestimated (four out
      of 52). All of the false negatives were solids whereas most of false positives
      were liquids, indicating that some adjustment in the protocol may be required
      depending on the physical state of the substance to be tested. All of the
      substances selected could be evaluated, with no limitation such as colour,
      insolubility, low or high pH. Given the number of products evaluated and the
      reproducibility within and among the laboratories involved, the overall results
      are quite satisfactory and therefore confirm the usefulness of the assay for
      screening chemicals for ocular irritation.

PMID- 20692930
TI  - The biochemical effects and toxicity of hydrazine in cultured rat hepatocytes.
AB  - Cultured rat hepatocytes were exposed to hydrazine for 4 hr, 17 hr or 4 hr
      followed by a 13-hr post-exposure period. Hydrazine was cytotoxic as measured by
      leakage of lactate dehydrogenase (LDH), caused depletion of ATP and inhibited
      protein synthesis. The cytotoxicity and depletion of ATP in cultures exposed to
      hydrazine for 4 hr was less than that previously reported in hepatocyte
      suspensions exposed for 4 hr (Ghatineh et al., Archives of Toxicology 1992, 66,
      660). The threshold cytotoxic concentration (20 mm) was also higher in cells in
      culture than in cells in suspension (16 mm). Inhibition of protein synthesis was
      detected at a much lower concentration of hydrazine (0.5 mm) than was required to
      deplete ATP (16 mm) or cause cytotoxicity (20 mm). ATP depletion and inhibition
      of protein synthesis were similar after a 4-hr exposure with or without a 13-hr
      post-exposure period, but leakage of LDH still occurred during this period. After
      the 17-hr exposure, the leakage of LDH, ATP depletion and inhibition of protein
      synthesis were greater and the threshold concentration of hydrazine required for
      a significant effect on all three parameters was lower. This was so whether
      compared with a 4-hr exposure, or a 4-hr exposure plus a 13-hr post-exposure
      period. The results of this study indicate the following: (a) the sensitivity of
      cultured hepatocytes to hydrazine is no greater than that of hepatocytes in
      suspension; (b) the duration of exposure to hydrazine is important but the effect
      depends on the parameter measured; (c) hydrazine causes a dose-dependent
      inhibition of protein synthesis at much lower concentrations than those causing
      LDH leakage; (d) maintenance of cytochrome P-450 in cultured hepatocytes by
      exposure to metyrapone did not alter the cytotoxicity of hydrazine.

PMID- 20692931
TI  - Effects of N,N-dimethylformamide and its degradation products in zebrafish
      embryos.
AB  - The response of zebrafish (Brachydanio rerio) embryos, cultured in reconstituted
      water, to continuous treatment with N,N-dimethylformamide (DMF) or its
      degradation products until hatching, was investigated. The embryos were
      distinctly susceptible to DMF, N-(hydroxymethyl)-N-methylformamide (DMF-OH), N
      methylformamide (NMF), N-acetyl-S-(N-methylcarbamoyl)cysteine (AMCC), and
      formamide (FA). Concentrations of 18 (DMF-OH), 121 (DMF), 163 (AMCC), 186 (NMF)
      and 203 (FA) mmol/litre produced 50% embryo lethality (LC(50)). Only treatment
      with DMF, NMF or FA induced malformations, involving curvature of the spine and
      tail and reduction of heart size and action with decreased blood circulation.

PMID- 20692932
TI  - Glucocorticoid potentiation of lead neurotoxicity in the mouse HN9 hippocampal
      cell line.
AB  - The biochemical events underlying neurobehavioural deficits following persistent
      low-level lead exposure during embryonic and early postnatal development remain
      unclear. Because glucocorticoids have previously been demonstrated to potentiate
      the action of certain neurotoxins, their role in low-level lead-mediated
      neurotoxicity was examined using a glucocorticoid-responsive immortalized
      hippocampal neural cell line (HN9). Low-level lead (10(-10)m) reduced the cell
      number by approximately 30% over a 5-day treatment period. This effect was
      potentiated by treatment with the synthetic glucocorticoid dexamethasone, with a
      52% decrease in cell number. Lead toxicity in actively differentiating cells was
      also potentiated by dexamethasone. However, while neither lead nor dexamethasone
      alone was toxic for cells that had previously been induced to differentiate, a
      combination of both drugs significantly reduced cell number. These results
      suggest that lead is preferentially toxic in actively dividing cells and that
      glucocorticoids may play a role in the potentiation of the lead-induced
      neurotoxicity.

PMID- 20692933
TI  - Effects of short-term exposure to ethanol on mouse embryos in vitro.
AB  - The adverse developmental effects of ethanol consumption have been documented in
      humans and in animal models. In animal models, the organ system affected by
      ethanol administration is dependent on the point in gestation at which the
      xenobiotic is administered. Previous studies have shown that an exposure of 24-48
      hr beginning at the early somite stage in rodent conceptuses alters neural tube
      closure in vitro. However, the concentration and time dependency of this effect
      have not been fully defined. Whole embryo culture was therefore used to expose 3
      6-somite mouse conceptuses (ICR strain) to ethanol at 300, 450, 600 and 800
      mg/dl. The higher concentrations were selected to approximate the peak serum
      ethanol concentrations that have been shown to be teratogenic in vivo. A 24-hr
      exposure produced a concentration-dependent increase in neural tube defects
      (NTDs) and concomitant growth retardation. When shorter exposure periods were
      used (8, 10, 12 or 20 hr) the incidence of NTDs was dependent on the ethanol
      concentration and exposure period. At the 600 and 800 mg/dl concentrations an
      exposure of 8 hr or more produced NTDs, but shorter periods (4 and 6 hr) did not
      affect neural tube closure when evaluated at the end of a 24-hr culture period.
      At the 450 mg/dl concentration a 20-hr exposure induced NTDs, but a 12-hr
      exposure to this level did not. Exposure of conceptuses to ethanol for periods
      similar to their half-life in vivo did not induce NTDs and the highest
      concentration produced only a trend towards a reduction in protein content. When
      the incidence of NTDs was plotted against the area under the time and
      concentration curve (AUC) the correlation coefficient was 0.5779. An analysis of
      covariance indicated that the relationships between NTDs and AUC were similar at
      the 300 and 450 mg/dl concentrations and also at the 600 and 800 mg/dl
      concentrations. In contrast, the relationships between embryonic protein content
      and AUC did not differ at the 300, 450 and 600 mg/dl concentrations, but all
      differed from that at the 800 mg/dl level. These results indicate that ethanol
      induced NTDs do not appear to be due solely to embryonic growth retardation.
      Additionally, ethanol-induced neural tube defects are a function of duration of
      exposure as well as of peak serum concentration.

PMID- 20692934
TI  - Effect of periportal- and centrilobular-equivalent oxygen tension on liver
      specific functions in long-term rat hepatocyte cultures.
AB  - The influence of periportal- and centrilobular-equivalent oxygen tensions on
      cellular functions and xenobiotic metabolism was investigated in rat hepatocytes
      cultured under 20% (air/CO(2)), 13% or 4% O(2) for up to 9 days on teflon
      membrane dishes, coated with crude membrane fractions and collagen. Protein
      content, total cytochrome P-450 content, 7-ethoxy-resorufin-O-deethylase (EROD)
      and the profile of hydroxytestosterone metabolites were not significantly
      affected by the oxygen tension, whereas intracellular lactate dehydrogenase
      activity and albumin secretion were increased at 4% O(2) in comparison with 13
      and 20% O(2) cultures. The induction of P-450 isoenzymes and corresponding
      catalytic activity was determined on days 4 and 9, following a 3-day exposure to
      phenobarbital (PB, 0.75 mm) or 3-methylcholanthrene (3-MC, 6.25 mum). On day 4,
      PB increased CYP2B1/B2 content 19-fold (4% O(2)) or 27-fold (13% O(2)), CYP2C6
      six-fold at both oxygen tensions, and CYP3A2 two-three-fold only in 4% O(2)
      cultures. On day 9, CYP2B1/B2 was still significantly increased. A clear
      correlation was found between P-450 isoenzyme content and corresponding isoenzyme
      activities, as assayed by testosterone hydroxylation and EROD activity on day 4.
      3-MC increased CYP1A1/2 11-fold and eight-fold in 4 and 13% O(2) cultures,
      respectively, and the EROD activity 37-fold (4% O(2)) and 30-fold (13% O(2)) on
      day 4. Activities were still measurable on day 9, whereas the corresponding
      apoproteins CYP1A1 was not detectable. These results suggest that hepatocytes are
      able to adapt their xenobiotic metabolism to different tissue oxygen tensions and
      confirm the likelihood that oxygen tension is an important modulator of the
      region-specific expression of xenobiotic metabolism in liver.

PMID- 20692935
TI  - In vitro cytotoxicity of neutrophil-like human HL-60 cells undergoing an
      oxidative burst with Escherichia coli reporter strains.
AB  - Neutrophil-like human promyelocytic HL-60 cells produced substantial amounts of
      reactive oxygen intermediates (ROIs) after stimulation with the tumour promoter
      phorbol myristate acetate (TPA). Escherichia coli PQ37 and PQ300 reporter strains
      incurred high levels of toxicity after co-incubation with neutrophil-like HL-60
      cells undergoing an oxidative burst. Toxicity was dependent on (a) the
      differentiation of HL-60 cells into neutrophil-like cells, (b) the stimulation of
      HL-60 cells with TPA and (c) the ratio of HL-60 to target cells. It is concluded
      that Escherichia coli PQ37 and PQ300 reporter strains can effectively be used to
      evaluate the cytotoxicity of neutrophils in vitro. The toxicity of HL-60 cells
      was, however, only marginally inhibited by the antioxidative enzymes catalase or
      superoxide dismutase. This indicates that, under the conditions chosen,
      cytotoxicity of HL-60 cells to Escherichia coli is mainly determined by factors
      other than ROIs and appears to be the result of complex interactions of the
      numerous reactive compounds that are released in addition to ROIs.

PMID- 20692936
TI  - In vitro percutaneous absorption of sodium arsenate in B6C3F(1) mice.
AB  - We report the investigation of the percutaneous absorption of sodium
      [(73)As]arsenate through skin of female B6C3F(1) mice under various conditions of
      exposure. In vitro diffusion experiments were conducted for 24 hr using
      previously clipped full-thickness dorsal skin in a flow-through system with HEPES
      buffered Hanks' balanced salt solution as the receptor fluid. Doses of 5, 50, 500
      or 5000 ng were applied to the skin surface (area = 0.64 cm(2)) as the solid
      compound, in aqueous vehicle (100 and 250 mul) or in soil (23 mg/cm(2)). Dermal
      absorption was quantified by summing the amounts of arsenate-derived
      radioactivity in the receptor fluid and skin following washing of the skin
      surface to remove unpenetrated compound. Absorption of sodium arsenate increased
      linearly with the applied dose from all exposure vehicles, with a constant
      fraction of the dose being absorbed. Maximum absorption (62% of the applied dose)
      was obtained from the 100-mul aqueous vehicle and the skin contained a higher
      level of the compound than the receptor fluid. Soil provided the least (<0.3% of
      the applied dose) absorption of the chemical, with the major portion (68%) of the
      absorbed dose residing within the skin. Even short-term (1 hr) dermal exposure to
      arsenate in water resulted in the passage of the chemical into the skin, which,
      on further perfusion (23 hr), passed into the receptor fluid. Thus, the exposure
      vehicle plays an important role in the in vitro dermal absorption of sodium
      arsenate in B6C3F(1) mice, with the aqueous vehicle providing greater absorption
      than the soil.

PMID- 20692937
TI  - Effect of indanyl analogues of diethylstilboestrol on morphological
      transformation of Syrian hamster embryo fibroblasts and micronuclei in vitro.
AB  - Two analogues of the carcinogenic oestrogen diethylstilboestrol (DES),
      indenoestrol A (IA) and indenoestrol B (IB), have been studied with respect to
      their genotoxic and cell transforming properties in mammalian cells. The
      conformation and oestrogenicity of IA and IB are very similar, but they differ
      with respect to their ease of peroxidation and the resulting reactive
      intermediates: only IA is readily converted to a p-quinone. Both DES derivatives
      caused morphological transformation of Syrian hamster embryo (SHE) fibroblasts
      with similar efficiency at concentrations (1 to 10 mum) that did not affect
      cloning efficiency. In addition, IA and IB (5 to 50 mum) induced micronuclei in
      the same cell system. These micronuclei were detectable as early as 1-3 hr after
      a 5-hr treatment with IA or IB. Such a time course is characteristic of compounds
      that cause mitotic disturbances. Indomethacin, an inhibitor of prostaglandin H
      synthase (the enzyme responsible for oxidation of DES in target cells), did not
      affect the frequency of micronuclei induced by IA or by IB. From these data we
      conclude that peroxidative metabolism resulting in quinone formation is not a
      prerequisite for the genotoxicity of these compounds. In addition to DES and
      several of its analogues the indanyl derivatives now also have been shown to be
      active in both of these short-term assays, suggesting that the in vitro
      micronucleus formation and morphological cell transformation are causally related
      events.

PMID- 20692938
TI  - Effect of the dihydropyridine dexniguldipine on the epidermal growth factor
      stimulated proliferation of human lung cancer cell lines.
AB  - The dihydropyridine Dexniguldipine (B859-35) has been shown to inhibit calmodulin
      and protein kinase C in vitro, and has a significant therapeutic effect on
      induced neuroendocrine lung tumours in hamsters. As phase I clinical trials with
      this agent resulted in the development of stable disease in several patients with
      non-small-cell cancers and preliminary in vitro studies revealed several non
      small-cell cancer cell lines susceptible to the antiproliferative effects of
      dexniguldipine, the possibility was investigated that this agent may inhibit cell
      proliferation stimulated by epidermal growth factor (EGF), which is expressed in
      many non-small-cell cancer types. Experiments conducted with six human lung
      cancer cell lines showed that dexniguldipine is a potent inhibitor of EGF
      stimulated cell proliferation. This agent may therefore also be useful for the
      therapy of cancers that express the EGF receptor.

PMID- 20692939
TI  - Anticholinesterase activity of the fusarium metabolite visoltricin and its N
      methyl derivative.
AB  - Visoltricin is a bioactive 4,5-disubstituted N-methylimidazole produced by
      Fusarium tricinctum, which shows toxic activity towards Artemia salina larvae and
      miotic activity on rabbit eye. The anticholinesterase properties and kinetic
      parameters of visoltricin and N-methyl visoltricin were assessed. Visoltricin
      anticholinesterase activity was demonstrated on human serum [median inhibitory
      concentration (IC(50)) = 2.6 x 10(-4)m], bovine erythrocyte acetylcholinesterase
      EC 3.1.1.7 (IC(50) = 4 x 10(-4)m) and human serum cholinesterase EC 3.1.1.8
      (IC(50) = 1.9 x 10(-4)m). The acetylcholinesterase inhibition constants (K(i)) of
      visoltricin and N-methyl visoltricin were 1.88 x 10(-4)m, respectively. Kinetic
      studies showed for both compounds a mixed-type inhibition, with partial binding
      of the inhibitor to the enzyme-substrate complex. Visoltricin was a reversible
      inhibitor of acetylcholinesterase, as it was not hydrolysed by the inhibited
      enzyme, and the inhibition in vitro was concentration dependent but not time
      dependent. The anticholinesterase activity could explain, at least in part, the
      miotic activity of visoltricin.

PMID- 20692940
TI  - Comparative study of the HET-CAM test and the Draize eye test for assessment of
      irritancy potential.
AB  - The ocular irritancy potential of different substances used as vehicles has been
      tested by the Draize test method and the alternative hen's egg test
      chorioallantoic membrane (HET-CAM) test. With the latter test,
      carboxymethylcellulose was not found to be irritant and can be used to suspend
      insoluble substances to be assessed by this method. The ocular irritancy
      potential of six commercial disinfectants was also tested by the Draize test
      method and the alternative HET-CAM test. Products were assigned to categories of
      irritancy, according to two different sets of criteria for the Draize test
      results, and according to irritancy potential assessed by the HET-CAM test. When
      both sets of results for Draize categories were compared with those for the HET
      CAM test, four of the six products tested showed similar irritancy potential. The
      remaining two products gave false positive results on the HET-CAM compared with
      the Draize test.

PMID- 20692941
TI  - Effect of glucose on lipid peroxidation and antioxidant enzyme activities in rat
      liver slices.
AB  - Glucose induced lipid peroxidation in rat liver slices and caused membrane damage
      to liver cells due to oxidative stress. Superoxide dismutase provided an
      antioxidant enzyme protection against the oxidative stress at low glucose
      concentrations (25-75 mm) but catalase showed no significant changes. The
      activity of both of these enzymes decreased in the liver slices at a higher
      concentration of glucose (150 mm). The glutathione content and the activity of
      glutathione S-transferase in the liver slices was decreased in the presence of
      glucose. The decrease in the glutathione content and glutathione S-transferase
      activity cause ineffective neutralization of the electrophiles. These findings
      indicate that glucose induces lipid peroxidation and alters the activity of
      superoxide dismutase and catalase in the liver slices. The decreased glutathione
      content and glutathione S-transferase activity may be the reason for increased
      lipid peroxides.

PMID- 20692942
TI  - Effects of procaine and two of its metabolites on cisplatin-induced kidney injury
      in vitro: Mitochondrial aspects.
AB  - The protective effects of procaine on cisplatin-induced kidney damage were
      studied with rat renal cortical slices in vitro. Cisplatin (2 mm) increased the
      leakage of the enzymes N-acetyl-beta-d-glucosaminidase, aspartate
      aminotransferase and lactate dehydrogenase from the slices into the incubation
      medium five-fold, 10-fold and 11-fold, respectively. Procaine (2 mm) protected
      against this cellular damage and decreased the leakage to 50, 65 and 29% of that
      caused by cisplatin. Protection was also observed when the slices were treated
      with two metabolites of procaine [diethylaminoethanol (DEAE) and p-aminobenzoic
      acid (PABA)], although these were slightly less effective than procaine.
      Cisplatin also increased mitochondrial lipid peroxidation to 177% of controls,
      and procaine, DEAE and PABA inhibited this cisplatin-induced increase by 24, 30
      and 22%, respectively. Procaine, DEAE and PABA had no effects, however, on either
      the loss of mitochondrial protein-sulfhydryls or the decrease of Ca(2+) uptake by
      the mitochondria that were caused by cisplatin. These observations suggest that
      the protection by procaine and its metabolites results from their inhibitory
      activity on the mitochondrial lipid peroxidation that was induced by cisplatin.

PMID- 20692943
TI  - Effect of mercuric ions on human erythrocytes. 1. Rate of haemolysis induced by
      osmotic shock as a function of incubation time.
AB  - Incubation of human erythrocytes with mercuric ions for 5 min causes a transient
      increase in mechanical resistance as measured by osmotic shock. After a longer
      incubation time (necessary for the metal to cross the cell membrane), cells
      recover their normal fragility; however, after 10-20 min of exposure to mercuric
      ions haemolysis occurs in the incubation vessel. In contrast, p-chloromercuriben
      zenesulfonate (a compound known to bind mainly to band 3 of the cell membrane
      without passing into the cell) increases the osmotic resistance of erythrocytes,
      as observed transiently for mercuric ions, but does not induce haemolysis even at
      incubation times of 20-30 min. Therefore it seems that the interaction per se of
      mercuric ions with the membrane does not represent the main damaging event and
      therefore the toxicological effect of mercuric ions must be mostly related to
      subsequent processes, such as the interaction of the metal with intracytoplasmic
      components and/or disruption of the cytoskeleton.

PMID- 20692944
TI  - Problems in using isolated and cultured hepatocytes for xenobiotic
      metabolism/metabolism-based toxicity testing-Solutions?
AB  - Isolated and cultured hepatocytes would seem to be an ideal model for the study
      of hepatic xenobiotic metabolism and metabolism-based hepatotoxicity. However, a
      serious drawback with this system of testing is the loss of xenobiotic
      metabolizing capacity in a reaction-dependent manner when the cells are kept in
      culture for any extended period. Many ways of modifying culture methods to
      overcome this problem have been investigated, for example the use of different
      culture media, culture media additions (e.g. hormones, serum, minerals, vitamins,
      and xenobiotics such as metyrapone and dimethyl sulfoxide), culturing on a
      substratum of components of the extracellular matrix or on microcarriers, and co
      culturing with other hepatic or with non-hepatic cells. However, these methods
      have achieved only limited success, with only some enzyme activities being
      preserved or many activities being preserved to only a limited degree.
      Furthermore, the variations between the methods used in hepatocyte isolation and
      culture preclude interlaboratory correlations of results. It is likely that a
      combination of the methods that have been investigated will yield a workable and
      reliable culture method to maintain xenobiotic metabolizing capacity in isolated
      hepatocytes, and co-ordination of research in this area should be promoted to
      achieve this outcome.

PMID- 20692945
TI  - Preface.

PMID- 20692946
TI  - Relevance of in vitro kinetic parameters to in vivo metabolism of xenobiotics.
AB  - Numerous in vitro systems are available for the study of pathways and kinetics of
      drug metabolism and the question is often posed of their utility as predictors of
      in vivo disposition behaviour. Of particular interest is the feasibility of
      predicting in vivo metabolic clearance of noxious chemicals in humans from data
      obtained in vitro using human tissue/gene expression systems. In theory the
      easily defined in vitro parameters V(max) and K(m) can be scaled to provide in
      vivo metabolic clearance. The cornerstone of this procedure is the parameter
      intrinsic clearance which may be defined biochemically as the V(max)/K(m) ratio.
      Extrapolation from the in vitro data requires scaling factors from either
      microsomal protein recovery, cellularity and/or organ weight and the use of a
      liver model (e.g. well-stirred liver) to express the kinetic data in terms of
      circulating drug concentrations (blood or plasma) rather than concentration at
      the enzyme site. The feasibility of this strategy and the relative merits of
      using hepatic microsomal and hepatocyte data will be discussed using a body of
      information on 25 drugs.

PMID- 20692947
TI  - The complement activation assay: The test for immediate phototoxicity.
AB  - A new in vitro test for phototoxicity has been developed. Nine substances (eight
      photosensitizers and one non-photosensitizer) were screened for their ability to
      activate human complement in the presence of UV light, and all photosensitizers
      were found to be active. Complement activation was quantified by means of ELISA.
      In all cases activation was mediated by alternative, but not by classical,
      pathways. The results of a cell culture test performed with 5-methoxypsoralen
      suggest the existence of two different mechanisms of phototoxicity. This
      indicates that the battery of in vitro assays for phototoxicity prediction must
      contain at least two different tests.

PMID- 20692948
TI  - Renal cytotoxicity of cisplatin in cultured glomerular mesangial and proximal and
      distal tubular cells.
AB  - Cisplatin is of considerable therapeutic value owing to its anti-tumoral
      activity. Unfortunately, its nephrotoxicity can reduce its clinical use. In vivo
      toxicity studies have shown large renal haemodynamic changes and differential
      tubular nephrotoxicity with strong proximal tropism. The present study compared
      renal cytotoxicity of cisplatin in three different cell cultures: glomerular
      mesangial cells and two renal tubular cell lines, LLCPK(1) (proximal) and MDCK
      (distal). Cell viability was assessed by the neutral red test. Cisplatin at 10(
      4)m induced a similar cell mortality in the three targets (about 80%). Mesangial
      cell mortality was concentration dependent, at 82, 31, 19 and 12% for 10(-4)-10(
      7)m, respectively. The IC(50) for MDCK cells was 5.35 x 10(-5)m compared with
      3.25 x 10(-5)m for LLCPK(1). For the different cisplatin concentrations mortality
      was two to three times higher in LLCPK(1), confirming the strong proximal tropism
      of cisplatin. These results demonstrate cisplatin cytotoxicity at both the
      glomerular and tubular levels, and open the way for comparative studies with new
      cisplatin derivatives for the optimization of their clinical use.

PMID- 20692949
TI  - Effect of peroxisome proliferators and inducers of xenobiotic metabolism on
      marker enzyme activities in cultured rat liver slices.
AB  - Previous work has demonstrated that precision-cut liver slices represent a
      valuable in vitro system for studying the metabolism and toxicity of xenobiotics.
      We have investigated their use for enzyme induction studies. Liver slices were
      prepared from male Sprague-Dawley rats and by using a dynamic culture system
      could be maintained in RPMI 1640 medium for up to 72 hr. The addition of 0.02-0.5
      mm concentrations of ciprofibrate, nafenopin and Wy-14,643 for 48 and 72 hr
      produced a concentration and time dependent induction of palmitoyl-CoA oxidation
      and carnitine acetyltransferase activities. Ultrastructural examination of liver
      slices revealed an increase in the number of peroxisomes. Liver slices were also
      cultured with 0.2-5 mm phenobarbitone, 5-50 mum beta-naphthoflavone and 0.5-20
      mug Aroclor 1254/ml and effects on the metabolism of 7-ethoxycoumarin, 7
      benzoxyresorufin and 7-ethoxyresorufin determined. All three compounds produced a
      concentration and time dependent induction of mixed-function oxidase enzyme
      activities. The results of this study demonstrate that rat liver slices can be
      cultured for up to 72 hr and appear to retain functional viability in that they
      respond to some known peroxisome proliferators and inducers of xenobiotic
      metabolism. Cultured liver slices may thus be a useful alternative in vitro
      system to hepatocytes for screening compounds for effects on various enzyme
      activities.

PMID- 20692950
TI  - Distribution of xenobiotic metabolizing enzymes in skin.
AB  - In the present study, the distribution and nature of specific xenobiotic
      metabolizing enzymes has been studied. Immunocytochemistry revealed the specific
      isoenzyme profile of the different cell types in mouse, rat and human skin.
      Constitutive levels of cytochrome P-450 1A1/A2 (CYP1A1/A2), CYP2B1/B2 and
      glutathione S-transferase were concentrated in the epidermis and sebaceous glands
      of all three species. Enzymic digestion followed by density gradient
      centrifugation resulted in fractions enriched in sebaceous cells, basal cells and
      differentiated keratinocytes. The basal and sebaceous cells of mouse skin were
      found to contain high levels of CYP1A1/A2, which was induced approximately 10
      fold following beta-naphthoflavone pretreatment. These findings suggest that
      xenobiotic metabolizing enzymes exhibit a similar qualitative distribution
      between the cell types of rodent and human skin and that these cell types may be
      isolated for use in mechanistic studies involving cutaneous metabolism and
      toxicity.

PMID- 20692951
TI  - Comparison of the cytotoxicity of ACE inhibitors and effects of cytochrome P-450
      and glutathione modulation in primary rat hepatocyte cultures.
AB  - Hepatotoxicity has been reported with angiotensin-converting enzyme (ACE)
      inhibitors. The mechanism of liver injury is not known. In the present study,
      primary rat hepatocytes were used to investigate the cytotoxicity of ACE
      inhibitors. Captopril, enalapril, fosinopril and quinapril were cytotoxic, as
      measured by lactate dehydrogenase release at 24 hr, with the rank order of
      toxicity as quinapril (LC (50) = 0.28 m m ) > fosinopril (LC (50) = 0.4 m m ) >
      enalapril (LC (50) = 2.0 m m ) > captopril (LC (50) = 20 m m ) . Enalaprilat, the
      de-esterified metabolite of enalapril, and lisinopril, the lysine analogue of
      enalaprilat, were not cytotoxic. In vivo pretreatment with pregnenolone-16alpha
      carbonitrile (cytochrome P-450 (CYP) 3A induction) enhanced the toxicities of
      enalapril, fosinopril and quinapril but did not affect the response to captopril.
      Induction with phenobarbital (CYP2B), beta-naphthoflavone (CYP1A) or ethanol
      (CYP2E1) did not influence the cytotoxicity of any of the ACE inhibitors. The
      hypothesis of a CYP3A-mediated bioactivation in the cytotoxicity of enalapril,
      fosinopril and quinapril was further supported by observations of reduced
      toxicity in the presence of SKF525-A and troleandomycin. The enhancement of
      cytotoxicity after pretreatment of the cultures with buthionine sulfoximine
      suggested a role for glutathione in protection, possibly by detoxifying unknown
      reactive metabolites.

PMID- 20692952
TI  - Lack of AFB(1)-induced mutagenicity in the in vitro hepatocyte micronucleus
      assay: Investigation of possible mechanisms.
AB  - Several mechanistic experiments were carried out to investigate negative results
      obtained with aflatoxin B(1) (AFB(1)) in the in vitro hepatocyte micronucleus
      assay. The data showed that the lack of AFB(1)-induced mutogenicity was not due
      to deficient metabolic activation of the mycotoxin or to an inefficiency of the
      test protocol. It appeared that the cytotoxic actions of AFB(1), specifically the
      interference with hepatocyte proliferation, prevented the formation of
      micronuclei.

PMID- 20692953
TI  - Inhibition of intercellular communication: An in vitro assay for detecting
      potential tumour promoters.
AB  - The effects of non-cytotoxic concentrations of 13 chemicals on gap junctional
      intercellular communication (GJIC) in human keratinocytes and WB 344 cells were
      determined using a scrape-labelling method. The chemicals were selected according
      to their reported tumour-promoting effects in either the skin or liver, or their
      known skin irritancy potential. The in vitro assay was able to discriminate
      between genotoxic and non-genotoxic chemicals and, with keratinocyte cultures,
      ranked correctly a series of phorbol esters with regard to their reported tumour
      promoting potencies in vivo. The data obtained support the suggestion that
      measurement of the inhibition of GJIC in vitro may provide a means to distinguish
      substances that have different tumour-promoting potencies.

PMID- 20692954
TI  - Toxicological insult of canalicular function in rat hepatocyte couplets: The role
      of calcium.
AB  - The biliary canalicular function of rat hepatocyte couplets was more sensitive to
      an increase in cytosolic calcium induced by A23187 (up to 30 mum) than by
      thapsigargin (up to 50 nm). This suggests that canalicular function was not
      disrupted by the release of endoplasmic reticulum calcium stores, although this
      was seen to stimulate canalicular contraction. Oxidative stress induced by
      menadione apparently disrupted canalicular function at non-lethal concentrations
      (up to 100 mum) by way of a mechanism other than the involvement of calcium.

PMID- 20692955
TI  - Study of the cardiotoxic potential of pharmaceutical compounds in chick
      myocardial myocyte reaggregate cultures.
AB  - Cardiotoxicity produced by doxorubicin in vivo is considered to be due to a
      direct effect on the myocardium and this is also a major component with toxicity
      of isoprenaline and digoxin. In the case of the cardiotoxicity produced at high
      doses by the antihypertensives hydralazine and pinacidil, an indirect mechanism
      operating by way of their exaggerated pharmacological effects is believed to be
      responsible. These compounds were examined for their cardiotoxic potential in
      vitro using chick myocardial myocyte reaggregate (MMR) cultures; allylamine HCl
      was used as a positive control. Cultures were incubated for up to 24 hr with each
      compound; parameters analysed were: spontaneous beating activity (SBA), lactate
      dehydrogenase (LDH) leakage and microscopic evidence of cytotoxicity. Allylamine,
      doxorubicin, digoxin and to a lesser extent isoprenaline were highly toxic to MMR
      cultures, as demonstrated by their effects on SBA, LDH leakage and morphology.
      Hydralazine showed very mild cytotoxicity at the highest concentrations with no
      LDH leakage; pinacidil was not cytotoxic but showed a dose-related inhibition of
      SBA. These results confirm the direct toxic action of doxorubicin and digoxin on
      myocardial cells and indicate that this is also an important mechanism in vivo
      for isoprenaline. The lack of any significant toxicity with hydralazine and
      pinacidil accords with an indirect mechanism based on their pharmacology.

PMID- 20692956
TI  - Detection and cellular localization of stress-induced 72 kD heat shock protein in
      cultured Swiss 3T3 mouse fibroblasts.
AB  - Cellular expression of the 72 kD heat shock protein (72 kD hsp) is increased
      following exposure to a wide range of physical and chemical stimuli and may be
      useful as a marker of cell toxicity. The primary objective of this work was to
      develop a cytochemical method suitable for the detection and cellular
      localization of stress-inducible 72 kD hsp mRNA and protein in cell cultures.
      Swiss 3T3 mouse fibroblasts, grown on multi-chamber glass slides, were
      transiently exposed to an elevated incubation temperature or various chemical
      agents and cellular 72 kD hsp expression visualized using immunocytochemical and
      in situ hybridization detection methods. Expression of 72 kD hsp was found to be
      dependent on the applied stimulus and recovery time. The combined culture system
      and cytochemical assay for 72 kD hsp provides a convenient method for studying
      cellular responses to a variety of toxins.

PMID- 20692957
TI  - Induction of mixed function oxidase activities in Cynomolgus monkey hepatocyte
      cultures.
AB  - Previous work has demonstrated that primary rat hepatocyte cultures may be used
      to screen compounds for induction of xenobiotic-metabolizing enzyme activities.
      In this study we have examined the effect of some known enzyme inducers in
      cynomolgus monkey hepatocytes. Cynomolgus monkey hepatocytes were isolated by a
      wedge perfusion technique and could be cultured in RPMI 1640 medium for at least
      5 days. Hepatocytes were cultured for 70 hr with 10 mug Aroclor 1254/ml, 10 mum
      beta-naphthoflavone (BNF), 2 mm phenobarbitone (PB) and 100 mum Wy-14,643. All
      four compounds induced 7-benzoxyresorufin O-debenzylase activity to 160-280% of
      control levels, whereas 7-ethoxyresorufin O-deethylase activity was induced by
      WY, PB, BNF and ARO to 165, 215, 605 and 1165% of control, respectively. These
      results demonstrate that cultured Cynomolgus monkey hepatocytes respond to some
      known enzyme inducers and hence may be useful for screening chemicals for
      induction of xenobiotic metabolism in primate liver.

PMID- 20692958
TI  - Skin metabolism of contact allergens.
AB  - Skin possesses metabolic capacity which may be significant for chemicals with
      direct skin effects. The conversion of some chemical contact allergens from an
      inactive to an active hapten has also been described. Eugenol and isoeugenol are
      contact allergens that fit this description, but despite close chemical
      similarity, they are not cross-reactive and this has led to the hypothesis that
      they may be activated by different mechanisms. There is evidence that eugenol
      follows a phenolic radical mechanism, while isoeugenol undergoes demethylation
      followed by oxidation to the orthoquinone. Since these reactions may be
      cytochrome P-450 mediated (the former being cytochrome P4501A driven) we
      investigated how modulation of this system affects skin sensitization to eugenol
      and isoeugenol. Using the local lymph node assay, which measures lymphocyte
      proliferation in draining lymph nodes, the effect of clotrimazole, an inhibitor
      of epidermal cytochrome P4501A, was assessed. Clotrimazole enhanced the response
      to eugenol and potassium dichromate (an irrelevant contact allergen)
      approximately two-fold and isoeugenol five-fold. It was anticipated that
      clotrimazole would have little effect on isoeugenol sensitization, but that
      through inhibition of cytochrome P4501A, eugenol sensitization would be reduced.
      However, the present data suggest that the presence of P4501A in skin may result
      in the metabolism of these chemicals to relatively harmless moieties.

PMID- 20692959
TI  - Effects of some non-genotoxic chemicals on DNA synthesis in rat hepatocytes.
AB  - The effect of the antihistaminic drug methapyrilene (MP) on DNA synthesis in
      primary cultures of rat hepatocytes has been compared with the effects of sodium
      phenobarbitone (PB), clofibric acid (CA), 2-acetylaminofluorene (AAF) and
      dimethyl sulfoxide (DMSO). The response for all chemicals was dependent on the
      concentration of epidermal growth factor (EGF) in the culture medium. MP at
      concentrations between 0.1 and 1 mum stimulated DNA synthesis. PB had a
      stimulatory effect on DNA synthesis at 0.5-1 mm. A greater increase in DNA
      synthesis was observed in the absence of EGF in the culture medium, for both
      chemicals. CA (0.1 mm) increased DNA synthesis in the absence of EGF and
      inhibited DNA synthesis at concentrations of 10 ng/ml or more. A dose-related
      increase in DNA synthesis with DMSO was observed in the presence of 10 ng EGF/ml.
      AAF did not stimulate DNA synthesis and inhibited it in the presence of 10 ng
      EGF/ml.

PMID- 20692960
TI  - Effects of foetal calf serum on cell viability, cytotoxicity and detoxification
      in the two kidney-derived cell lines LLC-PK1 and MDCK.
AB  - Foetal calf serum (FCS) dependent cell viability, cytotoxicity and detoxification
      were investigated in MDCK and LLC-PK1 cells. FCS was used at 0-10% (v/v).
      Viability and cytotoxicity were measured by neutral red uptake and by the MTT
      test. Viability of LLC-PK1 was strongly dependent on the FCS concentration, but
      that of MDCK cells only to a very limited extent. For both cell lines the
      cytotoxicity of HgCl(2) was FCS concentration dependent: lower toxicity was
      observed with 5-10% FCS than with 0-1% FCS. This effect was not observed for
      paracetamol. The results could not be explained by altered glutathione or
      glutathione S-transferase. The optimal FCS concentration of 1%, necessary to
      retain cell viability, had a limited influence on cytotoxicity. FCS concentration
      must be taken into consideration when cytotoxicity data from different studies
      are compared.

PMID- 20692961
TI  - Effect of alkylating and redox cycling quinones on insulin receptor
      autophosphorylation.
AB  - Autophosphorylation is thought to be an essential step in the insulin receptor
      signal transduction cascade. Previous studies have shown that thiol alkylation of
      the receptor can block this receptor autophosphorylation, whereas an oxidative
      environment can increase this process. Since the toxicity of quinones can be
      related to two mechanisms-redox cycling resulting in oxidative stress, and
      arylation of cellular nucleophilic groups-the effects of 1,4-naphthoquinone and
      menadione on insulin receptor autophosphorylation were investigated. The results
      show that these two quinones have a dual effect: lower concentrations leading to
      oxidative stress increase insulin receptor autophosphorylation, whereas higher
      concentrations cause a thiol depletion and inhibit the normal insulin receptor
      autophosphorylation.

PMID- 20692962
TI  - Toxicity of alpha-naphthylisothiocyanate in isolated hepatocytes: Possible role
      of taurine.
AB  - Exposure of isolated rat hepatocytes to alpha-naphthylisothiocyanate (ANIT)
      results in time and dose-dependent decreases in glutathione (GSH), ATP and cell
      viability. When taurine (15 mm) was added to cells no protection was afforded and
      a drop in the initial levels of GSH was also found. Prior treatment of rats with
      beta-alanine (3% in drinking water) did not increase ANIT toxicity, although
      taurine levels significantly dropped in cells. When 15 mm cysteinesulfinate was
      added to taurine depleted cells, some protection was afforded with a smaller drop
      in GSH than for cells incubated with buffer or taurine. The taurine pathway may
      thus play a protective role in ANIT cytotoxicity in isolated hepatocytes.

PMID- 20692963
TI  - Cytoprotective effects of taurine in isolated rat hepatocytes.
AB  - This study examined the protection of isolated rat hepatocytes against carbon
      tetrachloride, hydrazine and 1,4-naphthoquinone (1,4-NQ) toxicity. Hepatocytes
      were incubated with various concentrations of toxicant in the presence and
      absence of taurine (0-15 mm). The presence of taurine significantly decreased the
      cytotoxicity of each compound as measured by trypan blue uptake and lactate
      dehydrogenase leakage. The protection was related to the concentration of
      taurine, with a significant effect at 10 mm for all three compounds. When ATP was
      measured, however, taurine failed to protect against the depletion caused by
      hydrazine, whereas depletion due to 1,4-NQ was significantly ameliorated. The
      results suggest that taurine may protect cells from cytotoxicity as reflected by
      membrane damage but biochemical events underlying the toxicity, such as ATP
      depletion, may not be affected. Taurine may be a useful tool for the
      investigation of mechanisms of cytotoxicity.

PMID- 20692964
TI  - The effects of silymarin on the attachment and viability of primary cultures of
      rat hepatocytes.
AB  - The effects of the hepatoprotective compound silymarin on hepatocytes in primary
      culture were studied. Exposure of cells in primary culture (both conventional
      cells and perivenous or periportal cells isolated by the digitonin-collagenase
      perfusion technique) to high concentrations of silymarin surprisingly
      demonstrated that silymarin per se was cytotoxic. Incubation of cells for 18 hr
      with silymarin at concentrations exceeding 25 mum abruptly increased cell damage,
      whereas viability decreased in a more linear fashion with increasing
      concentrations of its major constituent, silybin. Morphologically, cell cultures
      exposed to silymarin concentrations lower than 20 mum appeared normal, but at
      higher concentrations intercellular contacts were lost; cells appeared granulated
      and took up eosin. Silymarin and silybin at these doses were also found to
      prevent cell attachment. The mechanism responsible for this effect at relatively
      low concentrations of silymarin during prolonged exposure in the primary cell
      culture system is not clear at present. The effects of low doses on cell
      attachment to the matrix suggest an action on the cell membrane and/or on the
      cytoskeleton.

PMID- 20692965
TI  - Comparative study of the hepatoprotective effect of silymarin and silybin on
      isolated rat hepatocytes.
AB  - The flavonoid silymarin and its main active component silybin have been used in
      the treatment of toxic liver diseases. In order to evaluate the hepatoprotective
      potency of both these compounds, their effects on the viability, lipid
      peroxidation and reduced glutathione (GSH) depletion induced by allyl alcohol
      (AA) and tert-butyl hydroperoxide (t-BuOOH) in suspensions of isolated
      hepatocytes were investigated. Cells were preincubated for 30 min with silymarin
      and silybin before the addition of AA or t-BuOOH. Samples were taken after 1-2 hr
      of incubation. Cell death, after 2 hr of incubation with 0.2 mm AA, was prevented
      by 0.01 mm silymarin; however, 2 mm silybin was required to give comparable
      protection. The presence of silymarin reduced AA-induced lipid peroxidation by
      more than 90%, whereas silybin was much less effective. The near-complete
      depletion of intracellular GSH by AA was restored in a dose-dependent manner by
      silymarin, but silybin did not have this effect. Protection by silymarin against
      the toxic effects of t-BuOOH was less pronounced than that against AA. In
      conclusion, silymarin was much more effective than silybin in preventing the
      toxic effects induced by two pro-oxidant toxins, AA and t-BuOOH.

PMID- 20692966
TI  - An in vitro embryotoxicity assay using the differentiation of embryonic mouse
      stem cells into haematopoietic cells.
AB  - The earliest identified state of a specific cell in mammalian embryonic
      development is the embryonic stem cell (ES cell). The murine ES cell line D3 was
      used to establish conditions that allow a reproducible differentiation of ES
      cells in culture. The development of haematopoietic cells in semi-solid medium
      parallels to some extent the onset of haematopoiesis in the developing embryo. In
      methylcellulose cultures, erythropoiesis is observed at day 7 to day 8 of
      culture. An inhibitory influence of retinoic acid is observed both on blood cell
      development and on myocardial cell development. In contrast, retinoic acid
      induces the development of nerve and skeletal muscle cell differentiation in D3
      ES cells. Further optimization of the culture conditions for ES cell
      differentiation will facilitate the use of ES cells for embryotoxicity testing in
      vitro.

PMID- 20692967
TI  - Use of model micro-organism to study cytostatics-membrane interactions.
AB  - A strain of Bacillus stearothermophilus was used as a model system to elucidate
      the interaction of tamoxifen with the cell membrane. This drug inhibits bacterial
      growth in a concentration-dependent manner. The inhibition increases at
      suboptimal and supraoptimal temperatures and is attenuated by the addition of
      Ca(2+) to the growth medium. Opposed physical alterations on bacterial membranes
      were observed when tamoxifen was added to the growth medium (increase in
      structural order) or directly in liposome preparations (decrease in structural
      order).

PMID- 20692968
TI  - Stimulant effect of nitrite on the activation of benzo[a]pyrene-7,8-dihydrodiol
      in human polymorphonuclear leucocytes.
AB  - Addition of sodium nitrite to human polymorphonuclear leucocytes (PMNs),
      previously treated with phorbol myristate acetate (PMA), significantly stimulates
      the activation of (-)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (BP-7,8-diol)
      to products that covalently bind to extracellular DNA and cellular proteins. The
      reactive metabolites formed from BP-7,8-diol have been identified as (+)-trans
      7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene [(+)-anti-BPDE], the
      ultimate carcinogen of benzo[a]pyrene, and benzo[a]pyrene-7,8-dione (BP-7,8
      dione). Isolated myeloperoxidase (MPO) in conjunction with hydrogen peroxide
      (H(2)O(2)) activates BP-7,8-diol to (+)-anti-BPDE. Addition of nitrite to the
      MPO/H(2)O(2) system markedly increased the formation of (+)-anti-BPDE. Taken
      together, the results indicate that the principal pathway for the nitrite
      stimulated formation of (+)-anti-BPDE in PMA-activated PMNs involves
      participation of MPO, whereas alternative pathways seem to be operative in the
      formation of BP-7,8-dione.

PMID- 20692969
TI  - Inhibitory effect of cysteine and methionine on free radicals induced by mercury
      in red blood cells of patients undergoing haemodialysis.
AB  - The inhibitory effects of cysteine and methionine on mercury-induced free
      radicals were studied in the red blood cells (RBC) of haemodialysed (HD)
      patients, using polyacrylonitrile membranes. RBC were taken from a control group
      of 10 healthy subjects and a group of 30 HD patients. The following were
      determined before and after HD: malonyldialdehyde (MDA), total glutathione (GST),
      reduced (GSH) and oxidized (GSSG) glutathione, and percentage haemolysis (before
      HD). RBC were incubated for 6 hr with mercury (Hg(2+); 10(-5)m), mercury and
      cysteine (0.001 m) and mercury and methionine (0.005 m). The percentage of
      mercury induced haemolysis differed between the control group and HD patients.
      The addition of cysteine and methionine to RBC has a markedly inhibitory effect
      on the mercury-induced haemolysis (a reduction from about 80 to 5% for cysteine
      and to 15% for methionine). MDA was increased in HD patients and increased
      further after HD. GST, GSH and GSSG were lower than normal in HD patients, both
      before and after HD. There was very little change in MDA concentration when the
      RBC were incubated with mercury for 6 hr.

PMID- 20692970
TI  - Use of scanning electron microscopy in the study of nephrotoxin-induced renal
      proximal tubular damage in vitro.
AB  - Scanning electron microscopy was used to study cephaloridine and gentamicin
      induced renal cell injury in vitro. Exposure of renal proximal tubular cells to
      these toxicants produced changes in cell surface morphology that occurred at
      concentrations similar to (or below) those affecting neutral red uptake or
      monolayer permeability.

PMID- 20692971
TI  - Effects of retinoic acid on the 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced
      differentiation of in vitro cultured human keratinocytes.
AB  - In order to study the interactive effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (TCDD), polychlorinated dibenzofurans (PCDFs) and retinoic acid on terminal
      differentiation of primary cultured keratinocytes derived from human foreskins,
      the amount of [(35)S]methionine-labelled proteins incorporated into cross-linked
      envelopes (CLEs) was determined. After isolation of the CLEs with sodium dodecyl
      sulfate, the amount of radioactivity collected on a filter was considered as a
      quantitative parameter for keratinocyte differentiation. Treatment of
      keratinocytes with different concentrations of TCDD resulted in a dose-dependent
      increase in differentiation, while only a minor decrease in differentiation
      occurred after treatment with retinoic acid. However, simultaneous application of
      10(-8)m TCDD and different concentrations of retinoic acid led to a dose
      dependent decrease in CLE formation. PCDFs exerted an effect on CLE formation
      similar to that of TCDD but with different potencies. We conclude that (1) TCDD
      induces a dose-dependent induction of human keratinocyte differentiation, (2)
      retinoic acid is a potent antagonist of TCDD-induced keratinocyte
      differentiation, and (3) primary cultures of human keratinocytes can serve as a
      useful model system to study the interactive effects of xenobiotics and hormone
      like substances on the regulation of differentiation.

PMID- 20692972
TI  - In vitro effects of thallium on mouse neuroblastoma cells.
AB  - To compare the effects of thallium at different cellular levels, cultured mouse
      neuroblastoma cells (Neuro-2A) were exposed for 24 hr to thallium(I) acetate. The
      following toxic indicators were assessed in the in vitro test system: cell
      proliferation by quantification of total protein content of the culture;
      cytoplasmic membrane integrity to cytosolic lactate dehydrogenase (LDH) leakage;
      lysosomal hexosaminidase release; lactate dehydrogenase activity; mitochondrial
      succinate dehydrogenase activity; relative neutral red uptake by lysosomes;
      lysosomal hexosaminidase sphingolipid degradation activity; acetylcholinesterase
      activity. The effects of thallium on the various indicators differed. Neural
      acetylcholinesterase activity was extremely sensitive to T1 inhibition. In
      contrast, hexosaminidase, an enzyme involved in glycosphingolipid degradation,
      was stimulated prior to cytoplasmic membrane disruption detected as LDH leakage.
      Relative neutral red uptake was slightly more sensitive than cell growth
      inhibition and the reduction in hexosaminidase release suggests an interaction
      with lysosomes. The low degree of sensitivity of cell proliferation, as judged by
      the protein content of the cultures, may reflect inhibition of protein
      degradation. LDH glycolytic activity was severely inhibited, but succinate
      dehydrogenase activity in the citric acid cycle was increased, probably owing to
      the mitochondrial accumulation of thallium.

PMID- 20692973
TI  - Bioactivation and bioinactivation of drugs and drug metabolites: Relevance to
      adverse drug reactions.
AB  - Adverse drug reactions that cannot be predicted from the pharmacological
      properties of the drug and which are not easily reproduced in laboratory animals
      are a major complication of drug therapy. It is necessary to investigate the
      mechanisms of such reactions in order to (1) define structural features within a
      given drug molecule which are responsible for causing toxicity and (2) to
      identify those individuals who are particularly sensitive to a given drug
      reaction. In theory, drug toxicity may arise by direct toxicity, genotoxicity or
      immune-mediated toxicity caused by either parent drug or chemical. In this
      respect chemically reactive metabolites are of particular importance and the
      balance between bioactivation and bioinactivation pathways of drug metabolism
      will be a critical factor in both the type and extent of toxicity. We have
      therefore developed in vitro techniques that incorporate human cells for the
      detection and characterization of stable, chemically reactive and cytotoxic
      metabolites. In such experiments bioactivation (by CYP1A, CYP2D6, CYP3A, etc.)
      can be investigated by use of a liver bank, while lymphocytes provide accessible
      human cells, which can be obtained from both patients and volunteers, genotyped
      and/or phenotyped for particular drug-metabolizing enzymes (eg. glutathione
      transferase mu). The relevance of in vitro experiments to drug toxicity observed
      in humans will be illustrated by reference to studies with anticonvulsants and
      antimalarials.

PMID- 20692974
TI  - A system to maximize the in vitro immunological stability of human Langerhans
      cells.
AB  - Langerhans cells (LC) are now known to be immunocompetent antigen-presenting
      cells (APC) that are involved with numerous immune reactions initiated in skin,
      including the induction of contact hypersensitivity and the rejection of skin
      grafts. Immortalized cells that closely resemble in vivo LC have not been
      developed and mature LC, in vitro, appear to only briefly pass through a stage of
      differentiation when immunological potential seems stable. The literature
      supports the concept that mature LC possess numerous ultrastructural and antigen
      (Ag) characteristics. These include suface ATPase activity, Fc receptors, MHC
      class II Ag, CD1a Ag and Birbeck granules. These studies were undertaken to
      determine the ideal conditions of LC isolation and enrichment for persistence of
      these characteristics, such that toxicological and immunoreactive studies could
      closely mimic the in vivo situation. Studies were carried out to evaluate sources
      of tissue, duration of manipulations, chemical perturbation, stored v. fresh
      tissue, methods of enrichment, donor serological information and cost. LC were
      evaluated for ultrastructural and Ag stability by light and electron microscopy
      utilizing monoclonal antibodies (Mab) to surface Ag and ultrastructural features.
      It was determined that the most critical conditions included duration of
      manipulations and method of enrichment. Differences between fresh-frozen and
      fresh tissue samples were negligible. Cells evaluated less than 18 hr post
      collection and enriched by density gradient centrifugation consistently
      demonstrated stability while ATPase activity, MHC Ag and ultrastructural
      characteristics varied when other methods were used. Implications for
      immunological and toxicological testing of in vitro skin samples can be drawn.

PMID- 20692975
TI  - Rodent and human mast cells as an in vitro model in neuroimmunotoxicity testing.
AB  - Mast cells derived from rodent or human tissues, either by direct lavage or
      following enzymic dispersal, secrete biogenic amines on challenge with a range of
      xenobiotics. In addition to synthetic pathways, re-uptake systems and
      metabolizing enzymes for histamine and 5-hydroxytryptamine, mast cells are
      responsive to neurotrophic factors, for example nerve growth factor (NGF). In
      these studies, rat peritoneal mast cells and human placental mast cells have been
      compared in terms of histamine release induced by a number of compounds. Of
      particular interest, it has been demonstrated that these mast cell populations
      functionally respond to NGF. Since NGF is essential to the development and
      survival of populations of nerve cells in the peripheral and central nervous
      systems, potential neurotoxicants or exogenously applied growth factors may
      interact with this trophic factor and/or its receptor to produce apparent
      toxicity. It is suggested that mast cells may be a suitable primary cell model
      for use in aspects of in vitro neurotoxicity and neuroimmunotoxicity testing for
      xenobiotics interfering with NGF function, for investigating the effects of
      neurotoxicants on monoamine function and for studying mechanistic aspects of
      neurodegenerative diseases.

PMID- 20692976
TI  - A three-dimensional in vitro model for the study of ocular cytotoxicity and
      irritancy.
AB  - A three-dimensional human tissue model has been developed in our laboratory and
      used as a substrate for assessing ocular cytotoxicity and irritancy potential.
      The full-thickness model is a co-culture of dermal fibroblasts and epithelial
      cells (keratinocytes). Metabolically and mitotically active fibroblasts are
      seeded onto medical-grade nylon mesh, where they attach and secrete collagen and
      extracellular matrix proteins. Then, keratinocytes are seeded onto the top of
      this submerged stromal tissue, and the tissue grows into a multilayered
      epithelium. Histological examination of this cellular co-culture system reveals a
      cellular organization similar to the rabbit/human cornea. The resulting substrate
      has been used effectively to study the effects of a variety of test compounds
      (surfactants, powders, creams) at diluted or full-strength concentrations in a
      time-course assay. The protocol mimics the way in which in vivo animal testing
      (Draize eye test) is performed. The treated tissue is assayed for cytotoxicity
      and irritancy (MTT and PGE(2), respectively) over a period of time. The high
      correlation (R > 0.81) of our in vitro data to existing animal eye data shows the
      potential usefulness of these tissue substrates as an in vitro alternative for
      evaluating the toxicity of test agents from diverse chemical classes.

PMID- 20692977
TI  - The use of in vitro reconstituted human skin in dermotoxicity testing.
AB  - As they simulate the multilayer tissue architecture present in vivo, three
      dimensional (3D) cultures of skin epithelial cells represent an attractive
      alternative for in vitro irritancy testing. In this study histology of non
      commercial (Skin recombinant on de-epidermized dermis) and commercial models
      (Episkin, ZK 1300, Living Skin Equivalent) was compared. All 3D models possess a
      stratified epidermis with a differentiated stratum corneum. Their barrier
      function has been demonstrated by comparison of surfactants cytotoxicity on the
      3D models and on human keratinocyte monolayer culture, and by the evaluation of
      the tritiated water penetration. All the 3D models showed permeability higher
      than fresh skin, the skin recombinant on DDED being the less permeable. However,
      reconstituted skin models possess several advantages for dermotoxicity testing,
      including the standardized nature of the epithelia and their suitability for
      testing water-insoluble compounds.

PMID- 20692978
TI  - Organotypic and epidermal-dermal co-cultures of normal human keratinocytes and
      dermal cells: Regulation of transforming growth factor alpha, beta1 and beta2
      mRNA levels.
AB  - Epidermal-dermal cell-cell interactions are recognized to influence keratinocyte
      proliferation in vivo as well as in vitro. To study the underlying molecular
      mechanisms of epithelial-mesenchymal interactions epidermal-dermal cell co
      cultures and organotypic cultures were used. Steady-state mRNA levels are
      described for transforming growth factors (TGF) alpha, beta1 and beta2, factors
      known to stimulate or inhibit the epidermal proliferation rate. In epidermal
      dermal monolayer co-cultures TGF alpha hybridization signals were absent. TGF
      beta1 mRNA was expressed in all cell types (keratinocytes, fibroblasts and
      microvascular endothelial cells), yet not regulated. In contrast, TGF beta2 mRNA
      was significantly induced in mesenchymal cells when they were co-cultured with
      keratinocytes. In organotypic cultures epidermal proliferation is dependent on
      the presence of fibroblasts within the gel. TGF beta1 was expressed at low levels
      in all cell types whereas TGF beta2 transcripts were not detectable at all. TGF
      alpha mRNA was present in keratinocytes at high levels, independent of epidermal
      cell proliferation or added epidermal growth factor. These results indicate
      complex regulative mechanisms for TGF alpha, beta1 and beta2 at the mRNA level.
      However, post-transcriptional steps are involved in the activation of TGF beta1
      and 2 and also have to be considered.

PMID- 20692979
TI  - Extended-term culture of human T lymphocytes: Material potentially useful in
      genotoxicity testing.
AB  - A simplified method, using recombinant interleukin-2, foetal bovine serum and
      freeze-killed feeder cells, has been developed for the mass culture of T
      lymphocytes derived from human peripheral blood. In this protocol, aliquots of
      bulk cultures can be cryopreserved about 8 days after initiation, and subsequent
      mass cultures generated a further week after recovery. At the end of this period
      the lymphocytes are karyotypically normal, and cultures from different donors are
      very similar in terms of rate of cell division and expression of key antigenic
      markers. Such extended-term T lymphocyte cultures are potentially valuable in
      genotoxicity testing, combining the practical convenience of established cell
      lines with the theoretical advantage of possession of the normal human karyotype.

PMID- 20692980
TI  - Reconstitution of human skin in vitro using readily available sources: Novel
      studies of tumour promotion.
AB  - As part of our development of an assay for skin tumour promoters we have
      standardized a three-dimensional model of human skin. The important features of
      this model for our purposes are (a) that it is characteristic of human skin, (b)
      that the developing epidermis can be seeded with "initiated" keratinocytes, and
      (c) that the calcium level of the medium can be controlled. The procedure used is
      an amalgamation of the methodologies of Asselineau and Prunieras (1984), Lenoir
      et al. (1988) and Rosdy and Clauss (1990). This model does not rely on a source
      of human skin and can be reproduced in any laboratory equipped with basic cell
      culture apparatus. The dermal equivalent consists of human embryonic fibroblasts
      and rat tail collagen. The overlying keratinocytes are derived from the outer
      root sheath of human hair follicles inserted into the collagen-fibroblast gel.
      Stratification is induced by culturing the epidermal cells at the air interface
      of a serum-free medium. The model has been characterized by histological
      staining, electron microscopy and immunostaining.

PMID- 20692981
TI  - Investigation of an in vitro cytotoxicity assay for prediction of skin
      irritation.
AB  - The ability of in vitro cytotoxicity to predict in vivo skin irritation was
      examined using three cell types and a set of previously examined chemicals with
      in vivo skin irritation data. There was concordance in ranking of the test
      chemicals according to their cytotoxicity between primary human keratinocytes
      (NHEK), NCTC 2544 and MDCK cells. When compared against rabbit in vivo skin
      irritation data, cytotoxicity to NHEK in serum-free media showed a better
      correlation (r(2) = -0.833) than the cell lines or NHEK in serum-containing
      medium. These are encouraging results for the use of cytotoxicity as an endpoint
      for the in vitro prediction of skin irritation.

PMID- 20692982
TI  - Cytotoxicity of 12 chemicals of known human and animal skin irritation potential
      in human keratinocyte cultures.
AB  - 12 chemicals were selected for cytotoxicity testing, based on a report of a
      collaborative study (EC Project 86E3-063/86-460) that compared in vitro
      cytotoxicity in animal cell models with animal irritation and non-invasive human
      in vivo data. Neutral red (NR) and acid phosphatase (AP) activity were chosen as
      endpoints of cytotoxicity. AP activity has been shown to be a specific indicator
      of cytotoxicity in keratinocytes. NR(50) values (concentration that produces a
      50% reduction in NR uptake compared with controls) and AP((peak)) values
      (concentration at which a peak activity occurs) were calculated for each
      chemical. Both in vitro assays exhibited good correlations with the animal
      irritation data. Poor correlations were obtained for comparison of the cutaneous
      blood flow volume data. The data presented provide useful information on the
      relationship between in vivo skin irritation and in vitro experimental models.

PMID- 20692983
TI  - In vitro tape stripping as a model for in vivo skin stripping.
AB  - Tape stripping is a useful technique to assess the distribution and amount of
      chemical in the stratum corneum (SC). The aim of this work was to develop an in
      vitro model that could be used to predict the results of in vivo skin stripping.
      Tape stripping experiments were carried out in vivo with the lipophilic penetrant
      fluazifop-butyl (FB) as part of a human volunteer study. Tape stripping was
      carried out at three time points after dosing. In vitro experiments were
      performed to match conditions in the in vivo experiment, using human epidermal
      membranes in static diffusion cells. By analysing the amount of penetrant in each
      pool of strips, the concentration profiles and the total amount of penetrant
      within the SC were determined from both in vivo and in vitro experiments. The
      concentration profiles demonstrate that the amount of penetrant decreases with
      increasing depth into the stratum corneum. The in vitro and in vivo profiles and
      total recovery of FB were found to be similar. These data suggest in vitro tape
      stripping provides a good model for the in vivo situation.

PMID- 20692984
TI  - Episkin: An in vitro model for the evaluation of phototoxicity and sunscreen
      photoprotective properties.
AB  - Exposure to UV radiation has been shown to induce cutaneous biological changes
      and chemical modifications of exogenous compounds. The application of sunscreen
      limits UV-induced cutaneous injury. Besides damages can also be elicited by some
      chemicals following UV irradiation (phototoxic agents). The effects of UVA and
      UVB irradiation have been studied in vitro on a reconstituted epidermis (EPISKIN)
      for cytotoxicity (MTT conversion test) and release of a proinflammatory mediator,
      interleukin 1alpha. When compared with irradiated human keratinocyte monolayers,
      the results obtained with EPISKIN showed the protective function of the stratum
      corneum to UVB. Topical application of a UVB sunscreen directly on EPISKIN
      stratum corneum showed a concentration-dependent relationship between the active
      ingredients and UVB-induced damages evaluated by both parameters. When
      chlorpromazine was tested on EPISKIN, an increase in cytotoxicity and release of
      interleukin 1alpha followed UVA irradiation. A non-cytotoxic dose of 10 J/cm(2)
      of UVA induced a 20-fold decrease in the chlorpromazine IC50. The chlorpromazine
      induced inflammatory reaction was also reflected by a more intense release of
      interleukin 1alpha in the underlying media of EPISKIN. Thus this proinflammatory
      mediator seems to be relevant as a phototoxic marker. The EPISKIN model may be a
      useful tool in the study of UV-induced cutaneous damage. The design of this study
      represents an advance in non-animal test development and could be of great
      interest in the determination of phototoxic or photoprotective effects of
      compounds in vitro.

PMID- 20692985
TI  - Influence of prior freezing on arylamine acetylation by human liver preparations.
AB  - Human liver tissue is an important resource for use in xenobiotic metabolism
      studies. Because of the scarcity of human livers, studies are frequently
      conducted with subcellular preparations from previously frozen material. The
      influence of prior freezing on arylamine acetylation with human S-9 was studied
      and differences were found between S-9 preparations derived from fresh liver and
      from stored frozen liver. Specifically, the capacity for formation of
      diacetylated benzidine was lost as a result of tissue freezing, and the rate and
      extent of monoacetylation appeared to be reduced also, though not as
      dramatically. These results demonstrate that freezing of human tissue prior to
      conducting metabolism studies with arylamines may alter metabolite profiles and
      indicate that, for reliable data, before using frozen human tissue in metabolism
      studies with arylamines one should check first for this possibility.

PMID- 20692986
TI  - In vitro studies of the toxicity of nucleoside analogues used in the treatment of
      HIV infection.
AB  - The nucleoside analogues, 3'-azido-3'-deoxythymidine (AZT, zidovudine), 2',3'
      dideoxyinosine (ddI, didanosine) and 2',3'-dideoxycytidine (ddC, zalcitabine),
      used in the treatment of human immunodeficiency virus (HIV) infection, have been
      associated with a number of dose-limiting toxicities in clinical studies. These
      include myelotoxicity (AZT), myopathy (AZT), peripheral neuropathy (ddC, ddI) and
      pancreatitis (ddI). Myopathy, peripheral neuropathy and pancreatitis are also
      observed in HIV-infected patients who have not been treated with the nucleoside
      analogues. Thus, nucleoside analogue toxicity can be confused with the adverse
      effects of HIV infection. Animal models exist for some, but not all, aspects of
      nucleoside analogue-related toxicity. In vitro studies have been used extensively
      to elucidate the mechanisms of nucleoside analogue toxicity. Cellular purine and
      pyrimidine metabolizing enzymes phosphorylate the analogues, which can then
      interact with DNA polymerases. Inhibition of one of these, HIV reverse
      transcriptase, is responsible for the antiviral activity of the nucleoside
      analogues. Toxicity is caused by inhibition of nuclear or mitochondrial DNA
      polymerases (or both) and by chain termination of replicating DNA at the point of
      insertion of the nucleoside analogue. The different toxicities observed in the
      case of each nucleoside analogue are most likely explained by different
      affinities for each of the cellular DNA polymerases.

PMID- 20692987
TI  - Epidermal cytokines and skin sensitization hazard.
AB  - The induction phase of skin sensitization is associated with the passage of
      antigen-bearing Langerhans cells (LC) from the epidermis to the draining lymph
      nodes. Recent investigations have revealed that the induction of LC migration
      following topical sensitization is dependent on tumour necrosis factor alpha (TNF
      alpha), an epidermal cytokine. While in transit to the lymph nodes LC are subject
      to both phenotypic and functional maturation which, by analogy with in vitro
      studies, is also effected by epidermal cytokines (granulocyte/macrophage colony
      stimulating factor, GM-CSF and interleukin-1, IL-1). It is now apparent that
      Langerhans cell function, the induction of cutaneous immune responses and
      effective sensitization are dependent on the availability of such cytokines and
      that contact allergens are able to provoke their production by keratinocytes and
      by Langerhans cells themselves. The development of screening strategies for the
      evaluation of skin sensitization potential as a function of epidermal cytokine
      production is discussed.

PMID- 20692988
TI  - Use of in vitro methodology to predict the irritancy potential of surfactants.
AB  - A battery of confirmatory and complementary in vitro assays was used to
      investigate a series of surfactants with different irritancy potentials, as
      confirmed by human skin patch testing. This was found to distinguish between
      sodium lauryl sulfate and its analogues, and when further tested on formulations
      the battery of assays was again capable of predicting the human data.

PMID- 20692989
TI  - In vitro assays for detection of diphtheria toxin.
AB  - Subunit-specific antipeptide antibodies have been used to develop a dot blot
      immunoassay for detection of diphtheria toxin (DT) produced by toxigenic strains
      of Corynebacterium diphtheriae. A detection limit of 0.1-1.0 ng DT/ml was
      obtained. DT is cytotoxic to cultured Vero cells and cell viability if
      conveniently assessed using a tetrazolium dye, MTT. This has been used as the
      basis of a cytotoxicity assay for DT, which has a detection limit of 20 pg/ml of
      biologically active toxin. Sixty isolates of C. diphtheriae were assayed for
      toxigenicity. There was complete concordance between the Vero cell cytotoxicity
      assay and guinea pig intradermal assay in vivo, demonstrating the utility of the
      cytotoxicity assay.

PMID- 20692990
TI  - The stem-cell test-A novel in vitro assay for teratogenic potential.
AB  - The micromass test for teratogens (Flint and Orton, 1984) has undergone extensive
      validation for use in reproductive toxicology. A major drawback of this test is
      its use of primary cells derived from rat embryos. The stem-cell test is a novel
      assay for teratogenic potential which uses a propagated cell line. Mouse
      embryonic stem cells (ESC) are maintained in an undifferentiated state in the
      presence of leukaemia inhibitory factor (LIF). On removing LIF, the cells
      differentiate into an embryonic endoderm that is morphologically distinct from
      ESC. Colonies of ESC are maintained from which cells can be harvested daily, and
      these cells, when washed free of LIF, form a population of differentiating cells
      on which the effects of chemicals can be tested. The conditions under which
      differentiating ESC can be substituted for rat primary embryonic cells in a
      micromass test protocol have been determined, and the effects of 25 compounds
      investigated in a blind trial. The stem-cell test predicted the teratogenicity of
      these compounds with a similar sensitivity and specificity to the micromass test,
      with the advantage that the test uses a propagated cell line; there is no use of
      animals.

PMID- 20692991
TI  - In vitro dermal toxicology using skin organ cultures.
AB  - In order to reduce animal discomfort and to obtain more quantitative endpoints,
      there is a need for reliable, preferably simple and inexpensive in vitro
      alternatives to skin toxicity testing. An in vitro model was developed in which
      full-thickness skin from various species can be cultured (rabbit, pig and human).
      Subsequent to topically applied test compounds, parameters of dermal toxicity
      were investigated, including cytotoxicity (MTT assay) and the release of
      inflammatory mediators (HETE's). Moreover, percutaneous absorption and concurrent
      biotransformation of compounds was studied. MTT conversion was inhibited in a
      dose-dependent manner following topical application of a wide range of irritants.
      Repair of initial damage was observed to some extent. The eicosanoid 12-HETE,
      which is thought to play an important role in chemotaxis, is released.
      Interestingly, the anti-inflammatory mediator 15-HETE was released only after a
      prolonged culture time of 48 hr, possibly indicating repair of the induced
      damage. The metabolic fate of the pesticide propoxur was investigated. Permeation
      rates were comparable in human and rabbit skin, while pig skin was found to be
      twice as permeable. Extensive cutaneous metabolism was observed in all three
      species.

PMID- 20692992
TI  - Risk assessment for mutagenic and carcinogenic activities of alpha,beta
      unsaturated carbonyl compounds by a screening strategy based on structure
      activity relationships.
AB  - alpha,beta-Unsaturated compounds are ubiquitous and are formed endogenously. They
      form DNA adducts and are a constant source of DNA damage. A speedy screening
      strategy based on structure-activity relationships and a battery of prescreening
      tests for a rapid and reliable assessment of the role of these compounds in
      mutagenesis and carcinogenesis is presented and discussed. In this screening
      strategy, time-consuming and expensive animal tests are replaced by in vitro test
      with bacteria and cell cultures. The results of the mutagenicity and genotoxicity
      tests, as well as the results of the binding studies of alpha,beta-unsaturated
      carbonyl compounds with DNA components, and the corresponding structure-activity
      relationships, are presented.

PMID- 20692993
TI  - Interleukin 6 production in vitro: An alternative read-out for the local lymph
      node assay.
AB  - The murine local lymph node assay has been developed as an alternative method for
      the identification of contact allergens. In contrast to guinea pig tests, which
      rely on visual assessment of challenge-induced dermal reactions, the local lymph
      node assay measures events occurring during the induction of skin sensitization.
      Contact allergic potential is measured as a function of hyperplastic responses in
      draining lymph nodes following systemic administration of [(3)H]thymidine. We
      have now examined whether the production in vitro of interleukin 6 (IL-6) by
      draining lymph node cells isolated from sensitized mice provides an alternative
      endpoint for the local lymph node assay. In comparative experiments, the
      production of IL-6 by lymph node cells in culture correlated closely with
      proliferative responses in vitro. Only chemicals known to cause contact
      sensitization elicited measurable (> 150 pg/ml) IL-6 production; non-sensitizing
      chemicals, including skin irritants, did not. Experience to date suggests that IL
      6 production may provide a useful alternative read-out for the identification of
      chemicals which have a significant skin-sensitizing potential.

PMID- 20692994
TI  - Safety evaluation of petroleum products using an in vitro eye irritation test
      battery.
AB  - An in vitro eye irritation test battery (IVEye) composed of the EYTEX and
      Modified Agarose Diffusion Method (MADM) assays was evaluated for use as a
      predictive, economical screen and/or adjunct for the Draize eye test. EYTEX
      mimics corneal opacification using a synthetic matrix of proteins that is
      intended to produce measurable opacity on exposure to chemical irritants in
      proportion to their ocular irritation potential. MADM is a cytotoxicity-based
      assay consisting of NCTC clone 929 mouse fibroblasts overlayed with 1% agarose in
      culture medium. Potential eye irritation is measured macroscopically as the area
      of decolorization (neutral red release) around the area of chemical application
      and microscopically as the percentage of cell lysis resulting from chemical
      application. Of the 70 materials tested in the IVEye for which Draize eye test
      data also exist, the battery correctly identified 38 materials as non-irritants
      and 30 as irritants, with two false positives and no false negatives. Non
      parametric analysis of the data show the battery to have a sensitivity of 100%, a
      specificity of 95% and a predictive value of 94%. The irritation class
      correlation (equivalence; irritation ranking) between EYTEX alone and the Draize
      data was 85%. These data support the use of IVEye as an accurate, reproducible
      and cost-effective in vitro method for identifying the eye irritation potential
      of petroleum products.

PMID- 20692995
TI  - The development and evaluation of in vitro tests for photoirritancy.
AB  - Photoirritancy, a reversible inflammatory reaction of the skin after chemical
      contact and UV radiation exposure, is increasingly observed as a side-effect of
      both cosmetics and certain systemic drugs. Despite the quantity of in vitro data
      available, none of the current animal models can be viewed as fully predictive of
      human exposure. It is therefore considered that the emphasis of future work
      should be the development and evaluation of in vitro assays. The aim of this
      study was to establish the interlaboratory performance of a physicochemical
      method, SOLATEX-PI. 12 pure chemicals at several concentrations were evaluated in
      the presence of UVA. In addition, a lymphoid cell assay was undertaken to allow a
      direct in vitro/in vitro comparison. The overall correlation between the
      laboratories was good when expressed in terms of a positive or negative result.
      However, there were some interlaboratory discrepancies, which were compounded by
      the lack of unequivocal in vivo data. Despite these discrepancies, both
      laboratories did agree on the final classification of nine of the 12 chemicals in
      the SOLATEX-PI system, based on the highest concentrations tested. The cellular
      photoirritancy assay, in contrast, predicted the correct classification for only
      eight of the 12 chemicals tested compared with the in vivo data supplied by IVI.

PMID- 20692996
TI  - In vitro alternatives for the detection of photoirritant chemicals: The
      EEC/COLIPA trial.
AB  - The effects of UV irradiation on the cytotoxicities of selected chemicals were
      investigated in cultures of Balb/c 3T3 cells, normal human keratinocytes and
      Jurkat cells. The chemicals were chosen according to their reported
      photoirritancy, or lack thereof, and the abilities of the in vitro tests to
      distinguish between these photoirritants and non-photoirritants were assessed.
      The data obtained suggest that the neutral red uptake assay with Balb/c 3T3 cells
      can be used to provide some indication of the potential photoirritancy of these
      particular chemicals. However, similar results were also obtained using the human
      keratinocytes and these should provide a more relevant in vitro model for
      investigating mechanisms of chemical-induced photoirritation.

PMID- 20692997
TI  - Effect of antivirals on human corneal cells in vitro.
AB  - Toxic effects of 10 antiviral substances [9-(2-hydroxyethoxymethyl)-guanine
      (ACV), E-5-(2-bromovinyl)-2'-deoxyuridine (BVDU), 5-(2-chloroethyl)-2'
      deoxyuridine (CEDU), 9-(1,3-dihydroxy-2-propoxymethyl) guanine (DHPG), (S)-9-(3
      hydroxy-2-phosphonylmethoxypropyl) adenine (HPMPA), (S)-1-(3-hydroxy-2
      phosphonylmethoxypropyl) cytosine (HPMPC), 5'-iodo-2'-deoxyuridine (IDU),
      phosphonoformic acid (PFA), 9-(2-phosphonylmethoxyethyl) adenine (PMEA) and 5
      trifluoromethyl-2'-deoxyuridine (TFT)] on uninfected human corneal cells were
      evaluated in two experimental models (undisturbed adherence and growth, and wound
      closure) under continuous drug exposure. The antiviral drugs were ranked in order
      of toxicity in each of the tests. The influence on toxicity of different
      experimental parameters such as initial cell density, length of exposure and
      trauma, was evaluated. There was significant interaction between toxicity and
      length of exposure. In undisturbed cultures antiviral compounds ranked as
      follows: PMEA </= DHPG </= ACV </= CEDU < PFA </= IDU </= BVDU << HPMPC < TFT <
      HPMPA. Wounding or migration increased the apparent toxicity of the antiviral
      substances; trauma did not have an additional effect. In conditions where corneal
      epithelium is poorly populated and ulcerated, wound healing can be delayed by
      antiviral medication.

PMID- 20692998
TI  - Intravitelline injection of rodent conceptuses: An improved in vitro
      developmental toxicity screen.
AB  - Many in vitro developmental toxicity screens are of limited usefulness, either
      because they lack the cell interactions of a whole embryo or because it is
      difficult to attribute an effect to the substance itself or a generated
      metabolite. Intravitelline injection into rat conceptuses during organogenesis
      bypasses the metabolically active visceral yolk sac and allows accurate delivery
      of specific drugs or their metabolites directly to the embryo. In a blind trial
      using 31 coded compounds, an overall accuracy of approximately 74% was achieved
      and four pairs of active/inactive analogues were distinguished. Additionally,
      thalidomide was shown to have teratogenic effects at low doses, mainly in the
      neural tube region.

PMID- 20692999
TI  - In vitro cytotoxicity studies of particulate samples in cultures of Hamster
      Tracheal Epithelial (HTE) cells.
AB  - Airborne contaminants have been implicated as important contributing factors in
      the aetiology of tumours of the respiratory tract. A major concern is that the
      potential carcinogenic activity of the particulate matter may be enhanced by the
      volatile material, which is adsorbed onto the surface. The cytotoxic potential of
      complex particulates was evaluated using the Neutral Red uptake method in primary
      cultures of hamster tracheal epithelial cells. Cytotoxicity of the reference
      particulates (benzo[a]pyrene adsorbed on to the surface of alumina A, alumina B,
      ferric oxide and titanium dioxide) was increased when cultures were treated with
      adsorbed rather than desorbed (plus dimethyl sulfoxide) samples. Foundry fume
      samples did not show the same effect.

PMID- 20693000
TI  - Use of a filtration plate in the MTT assay.
AB  - The use of the MultiScreen filtration plate enables fluids to be removed
      efficiently from the plate without disturbing cells, or formazan crystals formed
      during the MTT test. Using a 1:1 mix of dimethyl sulfoxide and ethanol as solvent
      allows optical densities to be measured directly on the Multiscreen plate. The
      possibility of washing cells without losses in their number appears to be
      advantageous especially for in vitro studies on cytokines and on the cytotoxicity
      of coloured substances, such as dyes. In this study the results of cytokine
      assessment using the Multiscreen plate were compared with those obtained using a
      normal flat-bottomed plate. Two methods of assessment of the cytotoxicity of the
      dye rose bengal were also compared.

PMID- 20693001
TI  - Differentiation of monocytes in vitro: Influence of different types of
      substances.
AB  - The monocyte is one of the cell types activated in inflammatory processes to
      leave the blood and to enter the site of tissue inflammation through the
      endothelium as part of the cellular infiltrate. In tissue, monocytes
      differentiate to macrophages. This process is characterized by the expression of
      differentiation antigens, which can be monitored by monoclonal antibodies. A set
      of monoclonal antibodies has been used to design a test to analyse the ability of
      substances to influence the pattern of antigen expression during macrophage
      differentiation. Irritant substances stimulate the enhanced expression of an
      'acute marker', which indicates the infiltration of macrophages into acutely
      inflamed tissues. Anti-inflammatory substances stimulate the enhanced expression
      of a 'middle marker' associated with the down-regulatory phase of macrophages.
      The stimulation of the 'acute marker' is positively correlated with the potential
      of substances and products to induce or elicit adverse skin reactions.

PMID- 20693002
TI  - In vitro analysis of immunoprotective effects of topical sunscreens.
AB  - The aim of this study was to evaluate procedures for the assessment of the
      immunoprotective capacities of topical sunscreens, using cell cultures. The
      exposure of humans to solar or ultraviolet radiation has been shown to induce
      numerous changes at the level of the immunoresponsiveness of the skin, which
      could be described as immune suppression. In this study, a sunscreen containing
      the commercially available UVB filters octyl triazone, phenylbenzimidazole
      sulfonic acid and methylbenzylidene camphor, was tested because of its capacity
      to protect from the immunosuppressive effects of UVB radiation. In contrast to
      control suncreens with a comparable sun protector factor (SPF), but that did not
      contain the UVB-filter octyl triazone, the immunoprotective sunscreen protected
      from two forms of immune suppression as assessed in vitro. Expression of the
      immune-relevant cellular communication structure intercellular adhesion molecule
      1 is decreased on the cell surface of epidermal cells under the influence of UVB.
      This effect of immune suppression is totally abolished by the immunoprotective
      capacity of the tested sunscreen, as monitored cytofluorometrically. The mixed
      lymphocyte reaction (MLR) was also used to assess the protective capacities of
      sunscreens against UVB-radiation-induced suppression of the immune response.
      Again, this UVB-induced suppression of the MLR was prevented by the sunscreen
      containing octyl triazone. In summary, the results of this study demonstrate the
      usefulness of the above-mentioned methods for the in vitro evaluation of the
      immunoprotective properties of topical sunscreens.

PMID- 20693003
TI  - Altered gene expression in immunotoxicology screening in vitro: Comparison with
      ex vivo analysis.
AB  - We have proposed in vitro immunotoxicology screening systems utilizing cDNA
      probes to monitor alterations in cytokine expression in defined cell populations.
      In this study we compared responses observed following in vitro exposure with
      responses in cells obtained ex vivo. Peritoneal macrophages and splenic
      lymphocytes were cultured from C3H mice or PVG rats and exposed to graded
      concentrations of the immunomodulators, biostim, cyclosporin A, azathioprine or
      tributyltin oxide (TBTO). Biostim (1 mug/ml) induced the expression of cytokine
      mRNAs in peritoneal macrophage cultures and induced a similar spectrum of
      cytokine expression in macrophages following administration to mice (100 mug/kg
      ip). Cyclosporin A (1 mug/ml) totally inhibited the expression of IL-2 mRNA in
      murine mixed lymphocyte cultures and induced a 40% inhibition of IL-2 mRNA in
      splenocytes isolated from mice repetitively exposed (5 x 100 mg/kg over 10 days).
      Azathioprine (10 mug/ml) inhibited the expression of all mRNAs in rat lymphocyte
      cultures and inhibited both IL-2 mRNA and actin expression in thymocytes isolated
      from PVG rats (2 mg/kg/day for 28 days). TBTO (10 nm) induced a 25% inhibition of
      an early peak of IL-2 receptor mRNA expression within mixed lymphocyte cultures
      and induced a 10% inhibition of expression of IL-2 receptor mRNA within mixed
      lymphocyte cultures from rats exposed to 50 mg/kg/day for 28 days. Our results
      demonstrate that appropriate batteries of in vitro tests can identify the four
      immunomodulatory chemicals described here. Observations made in vitro using
      molecular biological analysis have been shown to correlate with parallel ex vivo
      analysis.

PMID- 20693004
TI  - Combined in vitro assay for photohaemolysis and haemoglobin oxidation as part of
      a phototoxicity test system assessed with various phototoxic substances.
AB  - 12 well-known phototoxicants used in the EC/COLIPA (The European Cosmetic,
      Toiletry and Perfumery Association) interlaboratory validation trial on
      'Photoirritation in vitro' have been analysed in view of their ability to induce
      photohaemolysis. As well as, or instead of, this effect, oxidative reactions
      involving oxyhaemoglobin have been monitored, by assessing intra- and
      extracellular methaemoglobin formation, as an additional parameter in the
      screening of deleterious photoeffects on the cellular protein of red blood cells.
      A combination of both photohaemolysis and photo-oxidation of haemoglobin is
      proposed for the investigation of light-induced toxicity in an in vitro test
      system. Piroxicam and 8-methoxypsoralen did not produce any marked phototoxic
      alterations in this system. Rose bengal and amiodarone demonstrated predominantly
      membrane effects, whereas the antibiotics tetra- and doxycycline damaged
      exclusively the intracellular haemoglobin. All other phototoxins caused both
      photohaemolysis and photo-oxidation of haemoglobin.

PMID- 20693005
TI  - A screen for photoirritants in cultured cells.
AB  - Adverse photoirritant or photoallergic reactions may be caused by the interaction
      of certain chemicals with light. The behaviour of 20 chemicals (of which 12 were
      known UV absorbers and photoirritants, four were known UV absorbers and non
      photoirritants and four were known non-UV-absorbers and non-photoirritants) have
      been screened in an in vitro photoirritation assay using cultured cells [3T3
      neutral red uptake (NRU) assay]. Treated cells were exposed to UVA (5 J/cm(2) in
      50 min) and visible light in Earle's balanced salt solution and compared with
      dark controls. The 3T3 NRU assay has shown some promising results for screening
      photoirritants; however, it is likely that a battery of in vitro assays will be
      required.

PMID- 20693006
TI  - A cell culture model of isolated porcine urinary bladder epithelial cells for
      genotoxicity studies.
AB  - Monolayer cultures of porcine urinary bladder epithelial cells were obtained by
      isolating cells from bladders of freshly slaughtered pigs. The cultures were
      investigated morphologically and characterized according to their growth
      characteristics and enzymatic functions. Ultrastructural investigations
      demonstrated that the cells regain their in vivo polarization with apically
      situated membrane vesicles, tight junctions and desmosomes between neighbouring
      cells when they have built up a confluent monolayer. Membrane integrity and high
      cell viability was indicated by low levels of lactate dehydrogenase activity
      released into the medium. The chromosome set of the cells was stable during the
      first 5 wk of culture. Under standard culture conditions activities of the
      enzymes alkaline phosphatase and acid phosphatase were stable over a period of 4
      wk. gamma-glutamyl transpeptidase activity, indicating a dedifferentiation
      process, did not increase. Activity of NADH-dehydrogenase dropped, indicating a
      decrease in ER as a consequence of adaptation to the culture conditions. By
      measuring concentration dependent increase of sister chromatid exchanges (SCEs)
      induced by N-methyl-N'-nitro-N-nitrosoguanidine and 2-acetylaminofluorine, the
      suitability of this model for genotoxicity tests was estimated. These results
      indicate that the model can be used as a target for bladder cancer inducing
      agents to investigate the effects of such agents on the level of the target organ
      in further genotoxicity studies.

PMID- 20693007
TI  - Characterization of fresh mechanically isolated rat proximal tubule suspensions
      during prolonged incubation.
AB  - The majority of methodologies for tubule isolation involve the use of proteolytic
      enzymes to release the elemental nephronal regions from their connective tissue
      matrix. Although concerns have long been felt regarding potential structural
      damage incurred by the use of these enzymes, little has been done to characterize
      alternative non-enzymatic methods-with most of that being conducted on rabbit
      proximal tubules (PTs). The present work is performed on rat kidneys using the
      standard mechanical technique of Brendel & Meezan (1975), which involves
      perfusion, loading the renal vasculature with magnetic iron oxide, disrupting the
      cortex with a series of meshes, removing the glomeruli with a magnet and finally
      harvesting the rat PTs on a nylon mesh. The PTs were incubated in a 50% mixture
      of Ham's F12: Dulbecco's medium containing only penicillin and dextran as
      supplements. The viability and integrity of these PTs were assessed using
      morphology, enzyme leakage and oxygen uptake and were found to be well maintained
      in excess of 10 hr. It is now hoped to extend these measurements beyond 10 hr and
      to compare these measurements with those obtained with collagenase isolated PTs.

PMID- 20693008
TI  - In vitro toxicity of cephalosporin and aminoglycoside antibiotics to LLC-PK(1)
      cells assessed by changes in glucose uptake.
AB  - Nephrotoxin-induced damage to cultured kidney cells (LLC-PK(1)) was investigated
      using assays of general cytotoxicity (neutral red uptake) and of functional
      impairment (glucose accumulation). The latter correctly ranked both the
      cephalosporin and aminoglycoside antibiotics (acute and chronic proximal tubule
      toxicants respectively) in terms of their relative in vivo toxicities. Functional
      impairment after low-dose long-term exposure to the aminoglycosides occurred at
      sublethal drug concentrations. Assessment of general cytotoxicity correctly
      ranked only the aminoglycoside antibiotics.

PMID- 20693009
TI  - Assessment of membrane toxicity using [(3)H]arachidonic acid release in U937
      cells.
AB  - The release of arachidonic acid (AA) from membrane phospholipids is part of a
      signal system with which cells respond to environmental changes of various kinds.
      Using the promonocytic cell line U937, the kinetics of AA release was studied in
      [(3)H]AA-labelled U937 cells under the influence of various chemicals. Membrane
      toxic agents such as lysolecithin and sodium dodecyl sulfate (SDS) cause
      pronounced enhancement of [(3)H]AA release in U937 cells. The effect occurred
      immediately after exposure and proved to be dose-dependent, non-enzymatic and
      irreversible. With regard to mean [(3)H]AA-releasing rate in untreated U937
      cells, the following maximum tolerable concentrations were found: lysolecithin,
      0.5 mug/ml; SDS, 2 mug/ml; dimethoate, 31.3 mug/ml; chloramine, 160 mug/ml; 2,4
      dichlorophenoxyacetic acid (2,4-D), 1 mg/ml; formamide, 50 mg/ml and dimethyl
      sulfoxide, 100 mg/ml. AA release represents a highly sensitive bioindicator for
      the membrane-toxic effect of a chemical substance.

PMID- 20693010
TI  - The use of cultured skeletal muscle cells in testing for acute systemic toxicity.
AB  - A test system using primary cultured, spontaneously contracting, rat skeletal
      muscle cells has been developed to detect chemical interactions with excitable
      membranes. Taking into account some basic toxicokinetic differences between the
      in vivo and in vitro conditions, results obtained with the first 30 MEIC
      reference chemicals were quantitatively compared with in vivo acute toxicity
      data. The results show that the muscle cell test system is suitable for use in
      acute toxicity assessment and, for instance, for toxicity classification of
      chemicals.

PMID- 20693011
TI  - In vitro cytotoxicity testing of metal alloys used in medicine: Comparison of
      different approaches.
AB  - Metal alloys are used in medicine mainly for implantation in different branches
      of surgery and as indispensable materials in stomatology. The toxicity testing of
      these materials incurs even more technical problems than the toxicity testing of
      new drugs. In principle there are two approaches-direct contact of a tested
      material with cells, or toxicity testing of an eluate prepared from tested
      material. We have tested more than 20 different metal alloys, based either on
      titanium, gold or stainless-steel. We used three different in vitro methods: the
      dynamic assessment of contact cytotoxicity-cell monolayer is in direct contact
      with tested material (Cervinka and Puza, 1990); cell proliferation assessment
      effect of an eluate on cell proliferation is measured (Cervinka and Puza, 1990);
      agar overlayer with neutral red uptake-both effect of eluate and direct contact
      with tested material with agar overlayer could be measured. Based on our results
      we recommended to use all three approaches simultaneously in a battery of in
      vitro tests.

PMID- 20693012
TI  - The role of mechanistic toxicology in test method validation.
AB  - There are two approaches to in vitro toxicity test validation, phenomenological
      and mechanistic. The phenomenological approach uses correlative mathematical
      techniques, with no regard to the identification of mechanistic relationships, to
      relate in vitro measurements of toxicity to in vivo toxicological responses in
      order to establish the validity of the methods under consideration. This approach
      has three major limitations: (1) success or failure of a particular test will
      depend critically on the selection of test chemicals; (2) the reason why a
      chemical fails in a particular test is unknown; (3) without additional
      information there is no rational basis for extrapolation to new cases lying
      outside the domain of validation. The mechanistic approach addresses all of these
      issues: (1) mechanistic considerations are included in the selection of chemicals
      for validation; (2) the failure of a particular test to identify a given toxin
      means that the toxin does not act through the mechanism evaluated by the test,
      which is useful toxicological information; (3) any chemical that acts by the
      mechanism evaluated by the test will be identified. The major limitation of the
      mechanistic approach is our lack of knowledge concerning in vivo mechanistic
      toxicology.

PMID- 20693013
TI  - EEC/COLIPA project on in vitro phototoxicity testing: First results obtained with
      a Balb/c 3T3 cell phototoxicity assay.
AB  - In a joint validation project eight laboratories from the European Cosmetic
      Industry Association (COLIPA) as well as FRAME (England) and ZEBET (Germany) are
      trying to develop validated in vitro methods to be incorporated into new
      international guidelines for acute phototoxicity testing. The first stage of the
      study involved selection of the most promising in vitro phototoxicity tests for
      further validation. 20 chemicals with known phototoxic properties (12
      phototoxins, four UV-absorbing non-phototoxins and four non-UV absorbing non
      phototoxins) were tested under identical conditions of UV exposure conditions
      (sun simulator, UVA 5 J/cm(2)) in a standardized cytotoxicity assay with Balb/c
      3T3 fibroblasts (endpoint: neutral red uptake, NRU). 19 of the 20 chemicals were
      correctly classified by the 3T3 NRU phototoxicity test, and therefore, this
      simple assay for phototoxicity seems very promising and should be validated
      further.

PMID- 20693014
TI  - Evaluation of the EYTEX system as a screen for eye irritancy of petroleum
      products.
AB  - 89 petroleum products were tested in the EYTEX in vitro assay and the results
      were compared with data from Draize tests on the same materials. All 26 chemicals
      assessed as irritant in the Draize test were classified as irritant by the EYTEX
      assay; 61 of the 63 non-irritants were correctly classified by the in vitro
      assay. The correlation between the results from the EYTEX system and the Draize
      data was 89%, and the predictive value of the EYTEX system (percentage of EYTEX
      irritants that are true irritants) was 93%. When the same chemicals were tested
      in another laboratory, the coefficient of determination for the comparison of the
      EYTEX scores from the two laboratories was R(2) = 0.86. The results demonstrate
      the reliability and interpretability of the EYTEX assay carried out in our
      laboratory and therefore the viability, if not the validity, of this in vitro
      method as a screening test for the Draize assay.

PMID- 20693015
TI  - Phase 1 of an in vitro neurotoxicological pre-validation trial.
AB  - In the absence of a formal in vitro alternative model for neurotoxicity testing,
      the CellTox Centre, in collaboration with the University of Salford, FRAME and
      the EEC, has set up an initial pre-validation trial of a three-tiered scheme that
      was originally proposed in 1989. Using a cell battery of neuroblastomas and
      primary neural cultures (Tier I) and primary astrocytes (Tier III) an initial set
      of 20 chemicals (out of a reference set of 40 chemicals) has been assessed for
      neurotoxicity using a multiple end point assay system. The methods used were
      relatively simple, rapid and inexpensive, and the chemical end points were easily
      quantified. The results of the pre-validation trial have enabled us to revise the
      first tier of the proposed tiered system for full micro-validation.

PMID- 20693016
TI  - ECVAM: the European Centre for the Validation of Alternative Methods.
AB  - The European Centre for the Validation of Alternative Methods (ECVAM) has
      recently been established. The Centre will co-ordinate at Community level the
      validation of alternative test methods, maintain a database and act as a focal
      point for the exchange of information on alternative procedure, and carry out
      research and training. ECVAM aims to promote dialogue between legislators,
      industries, biomedical scientists, consumer organisations and animal welfare
      groups with a view to the development, validation and international recognition
      of alternative test methods.

PMID- 20693017
TI  - Principles for the validation of in vitro toxicology test methods.
AB  - This review addresses key aspects of validation of in vitro toxicity test methods
      as they have been presented by different authors during the last decade. The MEIC
      study is presented as a practical case in which several of these aspects have
      been considered.

PMID- 20693018
TI  - Definition of a new intralaboratory limit value for a positive UDS assay in
      vitro.
AB  - In our laboratory, we routinely perform the unscheduled DNA synthesis (UDS) assay
      in vitro using rat primary liver cells and autoradiographical evaluation. The
      fixed limit of +5 nuclear net grains (NNG) for a positive UDS response no longer
      seems to be appropriate because of the advanced techniques that are now used.
      Considering our historical data (mean vehicle control NNG of 45 experiments = 
      1.5; highest observed mean NNG value in 126 control slides = +1.63 NNG) we will
      use a mean value of +2 NNG as our new intralaboratory limit value for a positive
      UDS assay, independent of the statistical evaluation. Experiments with a mean NNG
      count in the vehicle control of > +0.5 will be rejected as invalid and repeated
      since mean values of > +0.23 NNG were never reached. Additionally, the NNG data
      obtained will be subjected to a newly proposed statistical method which includes
      both the actual and the mean historical control NNG value. First, the sum of the
      actual and the mean historical control value is divided by two. Secondly, the
      calculated control value is pairwise compared with the treated groups by the one
      sided Dunnett's test. This might be a helpful tool to evaluate a weak or
      equivocal UDS response.

PMID- 20693019
TI  - Use of astrocytes for in vitro neurotoxicity testing.
AB  - The use of primary cultures of astrocytes as indicators of toxic potential was
      assessed using 20 selected compounds. Multiple endpoints were used to evaluate
      astrocyte reactions. Trypan blue dye exclusion and total cellular protein content
      of the cells were used as general indices. EC(50) values from the trypan blue
      experiments could be used to rank toxicity of compounds in a manner that
      correlates well with known toxicity for compounds that have specific astrocyte
      toxicities. Neurone specific neurotoxicants had no measurable effects on
      astrocytes indicating that this system differentiates gliotoxicity from
      neurotoxicity. Protein content, and content of the astrocyte specific glial
      fibrillary acidic protein (GFAp), were seen to increase at lower doses of
      gliotoxic compounds. This phenomenon appears to be similar to reactive gliosis in
      vivo, as assessed by immunostaining, and is an extremely sensitive indication of
      cellular damage. Support studies using astrocyte uptake of 2-deoxy glucose showed
      a similar pattern of activation in the cells as protein increases. This has been
      confirmed using the nonisotopic technique of MTT reduction.

PMID- 20693020
TI  - The application of sulforhodamine B as a colorimetric endpoint in a cytotoxicity
      assay.
AB  - Sulforhodamine B (SRB), an aminoxanthene dye, has been used as an assay for total
      cell protein, initially developed as an endpoint assay for in vitro screening of
      antitumour agents. In this paper it was investigated as a possible endpoint for a
      cytotoxicity assay using CHO cells. It is a robust assay with a stable
      colorimetric endpoint, capable of semi-automation using microtitre equipment. At
      optimum concentrations (0.05-0.1% SRB) the assay is linear with respect to cell
      number over a range of 5 x 10(3) to 10(5) cells. In comparative studies with the
      neutral red assay the SRB assay was more sensitive, and in cytotoxicity assays
      with test compounds gave comparable dose-response curves. The cytotoxicity of
      five divalent metal chlorides was assessed using the SRB assay. The order of
      toxicity was Cd > Hg > Zn > Mn > Mg, that is similar to the expected in vivo
      ranking. 16 compounds with reported oral LD(50) (rat) ranging from 25,800 mg/kg
      (glucose) to 1 mg/kg (mercuric chloride) were tested in the assay. The relative
      toxicities of the compounds in the in vitro SRB assay were similar to the
      relative in vivo toxicities. The exceptions could be explained by the chemistry
      of the compounds and could be attributed to pharmacokinetic properties or
      mechanism of action. This assay can therefore be used to rank chemically similar
      compounds but is unsuitable as a precise predictor of in vivo toxicity.

PMID- 20693021
TI  - Skin sensitization structure-activity relationships for phenyl benzoates.
AB  - The key to determining whether a chemical has the ability to behave as a contact
      allergen must reside ultimately in the structure and properties of that chemical
      rather than in the immune system. Quantitative structure-activity relationships
      (QSARs) have been demonstrated for a small number of series of chemicals in the
      past, using the relative alkylation index model based on this principle. In the
      present work, a carefully chosen range of phenyl benzoate esters has been
      synthesized such that they would have a single mechanism of action but otherwise
      would span important areas of parameter space-reactivity, skin penetration
      characteristics and biological response. Computer-based methods of analysis were
      used to generate a QSAR. The model showed that molecular volume and particularly
      the calculated logarithm of the partition coefficient (ClogP) were key
      parameters. Surprisingly, while chemical reactivity is a requirement for skin
      sensitization, it was not found to be an important variable in the QSAR. In
      conclusion, the study confirms that within a series of related chemicals it is
      possible to derive a useful QSAR.

PMID- 20693022
TI  - Skin absorption: Flow-through or static diffusion cells.
AB  - Flow-through diffusion cells for the measurement of skin permeability in vitro
      are available commercially. We have designed a new system in our laboratory as an
      improvement on other cells. The CTL system is capable of running 15 cells
      simultaneously. In this study the flow-through diffusion system was compared with
      our well-validated and established static cell system, for ability to measure
      percutaneous absorption. Two hydrophilic chemicals-water and mannitol-were chosen
      as test penetrants. The permeability of whole skin, epidermis and dermatomed skin
      from humans, pigs, and rats was examined. The effect of tissue culture medium as
      receptor fluid was assessed in comparison with saline. Absorption data from the
      flow-through cells were similar to results from contemporary static cell. Thus,
      for each species and skin preparation there was good agreement in the
      permeability coefficients between the cell types. The absorption of the
      hydrophilic test penetrants into saline and tissue culture medium receptor fluid
      was also very similar. Further evaluation of this system, particularly for
      lipophilic molecules, is required.

PMID- 20693023
TI  - Quantitative concentration-toxicity relationship for the injury of rat thymocytes
      by chemical compounds used in inter-laboratory toxicity ring-tests.
AB  - Rat thymic lymphocytes were used to determine the cytotoxic effect of the two
      toxicants, 3,4-dichloroaniline (DCA) and sodium bromide (NaBr), at concentrations
      that have effects in the 21-day reproduction test with Daphnia magna. To evaluate
      the effect of the chemical compounds on cell membrane integrity, we measured the
      permeability of the thymocytes to trypan blue and the leakage of lactate
      dehydrogenase (LDH) from the cells. The viability and metabolic activity of the
      thymocytes were quantified by the MTT assay. The DCA concentrations tested (from
      31 to 310 nm) did not affect significantly the viability of thymocytes, as
      determined by trypan blue exclusion or by LDH leakage; however, with the MTT
      assay we could detect cytotoxicity at 62 nm. Both the trypan blue assay and the
      LDH assay indicated that concentrations of NaBr above 50 mm significantly
      affected the viability of the thymocytes. However, the MTT assay revealed a more
      pronounced toxic effect of NaBr, with significant cell damage being detected at 1
      mm.

PMID- 20693024
TI  - Use of in vitro methods to rank surfactants for irritation potential in support
      of new product development.
AB  - 11 surfactant raw materials with potential applications in light-duty liquid
      cleaning products were evaluated in vitro using a human skin analogue (ATS
      SKIN(2) Model ZK1100) for predicting cytotoxicity (MTT reduction) and
      inflammation [prostaglandin E(2) (PGE(2)) release]. Two of the 11 raw materials,
      both in the same compound family, were selected to be individually combined with
      each of the other nine in a 90:10 (raw:selected raw) mixture. Selection criteria
      were based on desired performance characteristics and low irritation potential as
      suggested from the individual surfactant assay data. To determine whether
      irritation potential was mitigated, MTT and PGE(2) scores were again determined
      for each of the 18 combinations with the resulting data being compared with the
      untreated raw material data. A plot of the data indicated that one of two
      selected materials may have an 'anti-irritant' effect. For raw materials with
      intrinsic MTT scores of less than 50 mug/ml and with the original data corrected
      for possible dilution effects, a statistical comparison between individual raw
      materials and the two sets of combinations was done using a one-sample analysis.
      Both cytotoxicity (MTT) and inflammation (PGE(2)) were significantly decreased by
      the milder of the two selected raw materials. By factoring the data into future
      new product decisions, this methodology has become a useful and practical tool
      for Amway product development.

PMID- 20693025
TI  - Development of an expert system rulebase for identifying contact allergens.
AB  - There are currently no in vitro methods for the identification of skin
      sensitizers (contact allergens). Knowledge relating chemical structure to
      toxicity can be programmed into expert systems. An historical database containing
      results of 294 defined single substances tested in the guinea pig maximization
      test to a single protocol has been used to derive a set of structural alerts for
      skin sensitization. Where possible, the approach used was to group the substances
      according to their most likely mechanism of reaction with skin proteins. Where no
      mechanism could be identified, structural alerts were derived empirically for
      groups of molecules with similar chemical functionality. This process has
      currently resulted in the production of 40 structure-activity rules, which have
      been incorporated into the expert system DEREK. Rulebases of this type have
      potential for use as a preliminary screen in toxicological hazard identification
      and may ultimately lead to a reduction in the use of laboratory animals.

PMID- 20693026
TI  - The UK Animals (Scientific Procedures) Act-Implications for the future of
      alternative toxicity tests.
AB  - The UK Animals (Scientific Procedures) Act 1986 requires a project licence for
      all potentially harmful animal tests in regulatory toxicology. Full consideration
      has to be given to alternatives, to the use of hierarchical strategies and to
      adherence to published guidelines. Advice on these matters is available from the
      Inspectorate. The mechanisms for developing and implementing policies on
      hierarchical strategies and alternatives are discussed. The paper notes some of
      the problems in the general context of toxicology, and uses as an example the
      Home Office guidelines on eye irritation tests published in 1987. These areas of
      regulatory toxicology tests are being considered currently by the Animal
      Procedures Committee.

PMID- 20693027
TI  - The ECITTS integrated toxicity testing scheme: The application of in vitro test
      systems to the hazard assessment of chemicals.
AB  - A multicentre project has been designed, with the purpose of developing the
      concept of integrated in vitro testing. The aim is to use non-animal methods to
      assess the toxicological properties of chemicals, and to improve this assessment
      through the use of knowledge of mechanisms of toxic action. A number of tests or
      test batteries were selected within eight areas: basal cytotoxicity, irritancy,
      developmental toxicology, hepatotoxicity, nephrotoxicity, immunotoxicity,
      neurotoxicity and biokinetics. For each area, a number of calibration chemicals
      were selected. In an initial pilot study, the neurotoxic properties of five
      chemicals will be studied in combination with a biokinetic analysis, in which
      blood and brain concentrations will be predicted from biokinetic modelling.

PMID- 20693028
TI  - An in vitro toxicity testing strategy for the classification and labelling of
      chemicals according to their potential acute lethal potency.
AB  - An in vitro test battery is described which consists of five systems using
      different types of cells: (1) bovine sperm cells, (2) Balb/c 3T3 cells, (3)
      primary cultures of rat hepatocytes, (4) primary cultures of rat muscle cells,
      and (5) co-cultures of microcarrier-attached rate hepatocytes and Balb/c 3T3
      cells. This combination of in vitro systems covers various aspects of cellular
      toxicity and permits determination of the intrinsic activity of chemicals with
      respect to general cytotoxicity, selective cytotoxicity and interference with
      selected cell-specific functions (Seibert et al., 1992). During the current phase
      of evaluation the different test systems are used in parallel, resulting in in
      vitro toxicity profiles which are the basis (a) for interpretation with respect
      to toxic potential, and (b) for the selection of appropriate assays for inclusion
      in a hierarchical approach to testing. Based on the experience with this test
      battery, a preliminary stepwise approach is proposed for the classification of
      chemicals according to their acute lethal potency. The principle steps and
      candidate tests are: (1) determination of cytotoxic activity (cytolethal and
      cytostatic)-sperm cells, 3T3 cell line; (2) determination of hepatocyte-specific
      cytotoxicity and of the role of bioactivation for cytotoxic activity-co-cultures
      of hepatocytes and 3T3 cells; and (3) determination of the potential of chemicals
      to interfere with electrically excitable membranes-muscle cell cultures.

PMID- 20693029
TI  - A strategy for the assessment of percutaneous absorption.
AB  - Percutaneous absorption can be a major route of entry into the body and its
      measurement is a critical part of risk assessment of chemicals contacting the
      skin. This paper outlines an approach for the assessment of a chemical's ability
      to penetrate the skin. Analysis of previously reported data has shown that the
      ability of a chemical to penetrate skin is dependent on its chemical properties.
      Using computational techniques, the physical properties of chemicals can be
      calculated and these are used to estimate permeability constants. At present this
      technique can only give a useful indication of a chemical's ability to penetrate
      skin. The use of properly designed experiments can improve this first estimation
      of percutaneous absorption but they can also give misleading results. The
      essential features of in vitro protocols are discussed. For chemicals shown to
      have a potential to penetrate skin, in vivo studies may be required for more
      accurate risk assessments.

PMID- 20693030
TI  - Strategic hierarchical approaches to acute toxicity testing.
AB  - Acute toxicity testing, including testing for irritation and sensitization,
      traditionally has relied heavily on animal models. While this situation has not
      yet changed dramatically, new developments and approaches offer opportunities to
      minimize or ultimately to eliminate altogether the use of animals in specific
      areas of acute toxicity. The value of a structured approach to toxicological
      evaluation in skin and eye irritation and contact sensitization is discussed in
      this report. The general approach is one of undertaking a thorough evaluation of
      existing knowledge, closely paralleled by consideration of chemical structure
      activity relationships, followed by appropriate in vitro testing, or, if there is
      no alternative, a limited animal study. Then only when absolutely necessary is a
      standard toxicology assay carried out, often to satisfy regulatory requirements.
      When ethically acceptable, the strategy may also include studies in humans. If
      these are done in a thorough manner, they may obviate the need for any animal
      work and should provide the most relevant toxicological assessment. By use of
      such a structured approach not only can some or all of the 3Rs be achieved, but
      data to support alternatives in regulatory toxicology can be generated.

PMID- 20693031
TI  - In vitro skin corrosivity test using human skin.
AB  - The in vitro skin corrosivity test (IVSCT) has been shown to be a reliable
      alternative for detecting substances that would be classified as corrosive in the
      standard in vivo test. The assay is based on the observation that corrosive
      substances produce a significant reduction in the transcutaneous electrical
      resistance (TER) of ex vivo rat skin. The use in the test of human skin to
      provide a means of direct assessment of potential corrosive substances in humans
      has been assessed. The testing of 12 substances allowed a TER threshold for in
      vitro classification as corrosive to be established. In further testing of 15
      surfactants (three classified as corrosive) and eight fatty acid substances (four
      corrosive), the three surfactants but none of the fatty acids were identified as
      corrosive in vitro. Thus the fatty acids labelled as corrosive, on the basis of
      animal data, may be incorrectly classified (i.e. in humans the substances would
      not lead to a corrosive effect following skin contact). It is envisaged that the
      IVSCT using human skin will be used together with human patch testing and lead to
      a reduction in animal testing and a more relevant classification of skin
      irritation potential to humans.

PMID- 20693032
TI  - Development of an in vitro test battery for use within a stepwise approach to the
      assessment of ocular irritancy in vivo.
AB  - The current OECD guideline for the assessment of eye irritation recommends,
      within its initial considerations, the use of data from skin irritation tests as
      a pre-screen to detect the most severely irritating materials, its being assumed
      that materials that are severely irritating to the skin are also significantly
      irritating to the eyes. However, analysis of data for 223 materials, tested in
      this laboratory for both dermal and ocular irritancy, revealed that only 23% of
      severe eye irritants were also severe skin irritants. This resulted in a
      significant number of rabbits developing severe ocular effects that had not been
      predicted from the dermal responses. This study reports the results of an
      alternative approach for predicting severe eye irritants. The approach was a two
      stage in vitro test battery; the first stage was a cytoxicity assay using the
      K562 cell line; the second was the isolated rabbit eye test. In contrast to the
      use of skin irritation tests, the in vitro battery was significantly more
      predictive (83% of severe eye irritants were detected). Although the indicence of
      false positive responses in the assay precludes its routine use as a replacement
      for the in vivo rabbit eye test, the test battery provides a powerful aid to
      reducing animal use and guiding in vivo studies to minimize the severity of
      effects.

PMID- 20693033
TI  - A comparison of two cytotoxicity tests for predicting the ocular irritancy of
      surfactants.
AB  - In vivo rabbit eye tests have attracted criticism on both scientific and ethical
      grounds. Consequently, there is a need to develop new approaches that still
      provide the necessary information on eye irritation hazard but that minimize or
      even avoid the use of whole laboratory animals. Cytotoxicity models have been
      used to predict the ocular irritancy of surfactants, since this class of
      chemicals has an essentially common action on cell membranes which involves
      membrane disruption. The aim of the present studies was to compare the predictive
      ability of two in vitro cytotoxicity tests, the K562 and the red blood cell lysis
      tests, in the assessment of the in vivo eye irritancy of surfactants. The results
      of these studies on 14 selected surfactant materials showed that the K562 assay
      was only modestly predictive of the in vivo response, with a specificity of 86%
      but a sensitivity of only 57%. In contrast, the red blood cell lysis test was
      more predictive, correctly identifying all irritants tested. In addition, all non
      irritant surfactants examined were predicted and a high (89%) ability to rank
      irritant effect was demonstrated. The red blood cell lysis test could be a
      powerful addition to a testing strategy or pre-screen for the evaluation of
      surfactant chemicals.

PMID- 20693034
TI  - Genotoxicity testing strategies.
AB  - Genotoxicity tests contribute to the assessment of whether a chemical has the
      potential to cause somatic or germ-cell effects in animals (i.e. the potential to
      induce cancer or heritable mutation). Such genotoxicity testing is usually
      undertaken in a stepwise approach; first an assessment in vitro, to determine
      intrinsic genotoxic activity, and secondly, an evaluation in vivo to determine
      whether any such activity is expressed in the whole animal. While this core
      principle is now generally accepted, there are still different opinions as to
      when, and how many, in vitro or in vivo assays should be conducted. Such
      strategies would be simplified and harmonized if testing was carried out based on
      the knowledge that there was a precedent for that strategy being required to
      detect a carcinogen or mutagen rather than the possibility that it might.

PMID- 20693035
TI  - Computational techniques for the prediction of toxicity.
AB  - Computational methods for the prediction of biological activity have been in use
      since the early 1960s. The application of these approaches in attempts to predict
      toxicological endpoints was reported within a few years of the establishment of
      the techniques, although early work was criticized on a number of grounds. This
      report reviews three approaches to the prediction of toxicity with examples of
      each approach. A new commercially available system (APEX) for the identification
      of pharmacophores (toxicophores) based on the three-dimensional structures of
      database compounds has been applied to a literature dataset of mutagenicity
      results. This program achieved a success rate of approximately 75% when trained
      on a set of 105 compounds; comparable results from other prediction systems,
      although trained on a much larger dataset, are approximately 85-90%.

PMID- 20693036
TI  - A role for in vitro cytotoxicity testing in the selection and development of
      metal-based pharmaceutical and materials products.
AB  - During the research and development process many similar chemicals or materials
      may be synthesized that accomplish the required task. The most promising examples
      then have to be selected for further development. This is primarily achieved by
      assessing performance in function tests. Where relative toxicity is important,
      cytotoxicity testing is an effective way of further ranking the potential
      products. Though cytotoxicity cannot be used to predict precisely in vivo
      toxicity, used in this fashion it can be successfully incorporated into the
      selection procedures of a product research and development programme. Four
      applications of cytotoxicity testing in an industrial research environment will
      be discussed. Primary screening of metal complexes for potential antitumour
      activity by evaluating selective cytotoxicity against a panel of human tumour
      derived cell lines. The cytotoxicity of a class of novel gold-phosphine complexes
      with antibacterial activity was assessed against the CHO cell line in order to
      select compounds with a favourable in vitro therapeutic index. The VERO cell line
      was used to assess the cytotoxicity of a number of AgCl/TiO(2) compositions with
      antibacterial activity as part of a biomaterials programme designed to produce
      materials suitable for incorporation into medical devices. Cytotoxicity against
      the CHO cell line was used to select possible components for new liquid gold
      compositions for application to ceramic materials.

PMID- 20693037
TI  - Development of a fixed-dose approach for the fluorescein leakage test.
AB  - To answer the question, "How toxic is this material?", rather than the question
      more usually asked in in vitro toxicology, "At what concentration does this
      material produce a given degree of toxicity?", a fixed-dose approach has been
      developed with the FRAME fluorescein leakage (FL) test. Recovery from the initial
      cytotoxic effect was also noted sometimes, after the cells had been maintained in
      fresh medium for a further 72 hr. Chemicals rated R41 or R36 in vivo gave a level
      of FL above 20% immediately, and 66% or more 72 hr later (i.e. there was further
      deterioration, rather than recovery). Acetaldehyde, when duplicated and tested
      either in Hanks' balanced salt solution or oil, showed greater toxicity in the
      oil because of its high volatility. The chemicals classified as no-label gave FL
      values below 12% immediately after exposure, except Brij-35, which showed no
      further deterioration during the 72-hr period in fresh medium.

PMID- 20693038
TI  - A Quantitative Structure-Activity Relationship (QSAR) for prediction of
      alpha(2mu)-globulin nephropathy.
AB  - A number of chemicals induce a toxic syndrome in male rats-referred to as
      alpha(2mu)-globulin nephropathy-that is characterized by an accumulation of the
      urinary protein alpha(2mu)-globulin in renal lysosomes, subsequent cytotoxicity
      and cell death. Binding affinity to alpha(2mu)-globulin has been identified as
      one of the determinants for alpha(2mu)-globulin nephropathy. A quantitative
      structure-activity relationship (QSAR) has been derived by multiple regression
      analysis relating this binding to negative charge density of the binding molecule
      and its molecular volume. Previous data, correlating aliphatic and alicyclic
      hydrocarbon structures with ability to induce renal lysosome accumulation in male
      rats, were analysed by the technique of principal components analysis applied to
      the molecular volumes and principal inertial axes of alcohols predicted to be
      derived from the hydrocarbons. Mapping of the first and second principal
      components showed clustering of molecules relative to their biological activity.
      A combination of the two QSARs is useful in identifying molecules with a
      potential to cause alpha(2mu)-globulin nephropathy.

PMID- 20693039
TI  - New epidermal model for dermal irritancy testing.
AB  - An interlaboratory comparison of a new model of the human epidermis (EpiDerm) was
      conducted using a range of anionic and non-ionic surfactants and surfactant
      containing final formulations. The toxicity of the materials was estimated by MTT
      conversion, using both concentration (EC(50)) and time (ET(50)) protocols. A
      range of 16 compounds was tested on different production lots of EpiDerm
      following storage periods of 1 and 2 days (after shipping) at MatTek and at two
      independent testing laboratories, Microbiological Associates (MA), USA and
      Scotland, UK. The EC(50) and ET(50) values were compared and the least squares
      fit lines with resulting correlation coefficients (r) calculated. Correlation of
      in vitro results to human clinical chamber irritation and repeat handwash testing
      gave r values ranging from 0.977 to 0.993 and comparison of the results obtained
      in the independent laboratories with the site of manufacture was good (MA, USA, r
      = 0.84; MA, UK, r = 0.74). The model appears to have utility in predicting
      clinically observed dermal irritation in vitro which is reproducible in different
      laboratories and after transatlantic shipping, such that it is worthy of further
      investigation.

PMID- 20693040
TI  - The use of in vitro methods in the ocular irritation assessment of cosmetic
      products.
AB  - The ocular tissue is a complex system consisting of corneal and conjunctival
      epithelial cells, the underlying corneal stroma and associated endothelial cells.
      Exposure to chemicals may result in responses ranging from mild, slight redness
      and itching, to severe injury with loss of corneal epithelium, damage to stroma,
      inflammatory infiltration and loss of vision. This complexity hinders the
      development of in vitro methods able to replace animal testing. Various in vitro
      techniques have been proposed and subsequently developed as potential
      replacements for ocular toxicity screening on animals. Over the past 2 years,
      eight methods have been evaluated in these laboratories. The endpoint of these
      methods could be linked to one or to several clinical events occurring in the in
      vivo eye irritancy process described above. Using these systems, a battery of
      four complementary in vitro assays has been developed. For the categories of
      ingredients and cosmetic products investigated, the promising results obtained
      suggest that in vitro methods of ocular risk assessment may be used increasingly
      in the future.

PMID- 20693041
TI  - Barriers to the acceptance of in vitro alternatives.
AB  - Despite a considerable effort by the scientific community over many years, the
      replacement of traditional animal tests by in vitro alternatives has not yet been
      achieved. Why are in vitro alternatives not more widely accepted by scientists
      and regulators? Barriers to acceptance, both overt and covert, must be recognized
      and surmounted if further progress is to be made. At least seven barriers to
      acceptance of an in vitro method will be discussed. VALIDATION: has it been
      adequately validated? Scientific: is it based on good science? Legislative: can
      it replace an OECD Guideline? DEVELOPMENT: has it been developed in another
      laboratory? Psychological: will it make traditional skills redundant? Litigation:
      will it stand up to legal scrutiny in court? Regulatory: will regulators modify
      their traditional hazard assessment criteria?

PMID- 20693042
TI  - Acceptance of in vitro studies by regulatory authorities.
AB  - There has been relatively little progress regarding the acceptance of in vitro
      tests by regulatory authorities since the second Practical In Vitro Toxicology
      Conference in 1989. Advances have been made in the international acceptance of
      the use of in vitro methods to identify compounds with mutagenic potential. The
      recognition, in international guidelines on skin and eye irritancy studies, of
      the need for a hierarchical approach, including the use of in vitro methods to
      screen out severe irritants, has also been welcome. The reasons for the
      relatively slow progress are considered. In the case of repeated-dose animal
      toxicity studies, these represent an effective broad-spectrum approach to
      identifying the general toxic effects and target organs. It will be difficult to
      design in vitro methods capable of mirroring the complex interactions seen in the
      whole animal or the multitudes of potential targets for toxic effects. In vitro
      studies may, however, be valuable in characterizing such effects once identified
      from the animal studies. Similar considerations apply to teratogenicity, where
      possible mechanisms include disturbances in placental function or in maternal
      metabolism. These examples illustrate the fairly substantial scientific obstacles
      that exist in some areas. The relatively rapid acceptance of mutagenicity studies
      was, to some extent, due to their single, underlying mechanism, namely, damage to
      DNA. In view of these problems, effort has concentrated on local effects such as
      skin and eye irritancy. Even here, the in vivo response is a complex series of
      reactions, and there is the assumption that a battery of in vitro tests will be
      needed. There have been difficulties in identifying the most promising
      combination of tests to subject to detailed validation. In addition, the number
      and identity of the 'reference' chemicals to be used and the comparative data (in
      vivo animal data or human data) needed has proved to be a matter of much debate.
      In addition to these difficulties, the need for international acceptance of the
      validation data has necessitated the adoption of a more international
      perspective. However, a large international study is now underway which, it is
      hoped, will lead to some real progress in the eye irritancy area.

PMID- 20693043
TI  - The use of in vitro methods for studying drug metabolism to replace animal
      studies as part of veterinary medicines product licence applications.
AB  - It is currently necessary to carry out drug metabolism studies in the target
      species as part of veterinary Product Licence Applications (PLA). Such studies
      use large numbers of animals. Studies with pig and rat liver homogenates obtained
      from animals slaughtered for human consumption have demonstrated that antipyrine
      shows the same metabolic differences between these species as would be expected
      in vivo. Continuation of these studies in sheep liver homogenates demonstrated
      species differences in the metabolism of antipyrine between sheep and pigs. In
      addition, ruminant isolated cell systems have been used to demonstrate
      differences in sulfadimidine metabolism between rats, goats, sheep and cattle.
      With the increasing availability of farm-animal isolated hepatocyte systems and
      mounting evidence that species differences in vitro reflect the in vivo
      situation, the time is right for such data to be submitted as part of veterinary
      medicine PLA.

PMID- 20693044
TI  - Updated toxicology test methods for new industrial chemicals: Implications for
      regulatory acceptance of in vitro alternatives now and in the future.
AB  - Toxicology studies submitted under the Notification of New Substances Regulations
      are conducted according to standard ('Annex V') methods first published in 1984.
      In December 1992, updated methods became available that indicate where progress
      has been made in developing in vitro alternatives to animal testing which are
      acceptable to the regulatory authority (Health and Safety Executive). Although
      some changes reflect concern for animal welfare (e.g. the introduction of the
      fixed-dose method), for most toxicological endpoints an animal test remains
      obligatory. The major advance in the potential use of in vitro methods is as part
      of a tiered approach to irritancy testing. The updated method for eye irritation,
      for example, allows positive results in 'well-validated alternative studies' to
      override the need for an animal test. The substance is then classified as
      irritant and labelled with R41. The challenge facing such methods is to achieve
      full validation, so that negative data will be acceptable to the regulatory
      authorities. There are other challenges: a validated in vitro screen for
      developmental toxicity is needed for new substances, as are methods for detecting
      respiratory sensitizers and for replacing guinea pig skin sensitization tests.

PMID- 20693045
TI  - Why, when and how in vitro tests should be accepted into regulatory toxicology.
AB  - The use of in vitro techniques in toxicological research is widespread, but, up
      to now, relatively little progress has been made in applying the knowledge gained
      in regulatory toxicity testing. In vitro tests should be accepted into regulatory
      toxicology for at least five reasons: scientific, humanitarian, legislative,
      logistical and economic. In particular, in vitro tests have the potential to
      provide a mechanistic basis for toxicity testing, and they may permit the use of
      tissues from more-appropriate target species and individuals, including humans.
      The relevance and reliability of the in vitro test, with regard to its use for a
      particular purpose and with particular types of chemicals, should have been
      adequately demonstrated (i.e. it should have been validated) prior to regulatory
      acceptance. There are several obstacles to this, including whether validation
      should be based on comparisons between in vitro data and animal data, and whether
      the in vitro tests should be expected to provide regulators with the same kinds
      of predictions and classification criteria that they currently obtain from animal
      tests. Regulatory incorporation should be a permissive process, rather than a
      restrictive one. Any scientifically defensible in vitro test which has been
      properly validated and independently recommended, should be acceptable for the
      specific purposes for which its use would be appropriate.

PMID- 20693046
TI  - Principles for a pragmatic approach to the regulatory acceptance of alternative
      tests.
AB  - Toxicity studies are conducted with a view to identifying and assessing human or
      environmental hazards. Thus, the key issues are those of which, and how much,
      information is considered necessary to make a reliable and valid assessment, and
      to what extent alternative tests can contribute to this assessment. In this
      respect, the following fundamental aspects are of relevance. Toxicology as a
      science focuses on the identification and characterization of adverse effects
      following exposure to chemicals by integrating all available information,
      including physicochemical properties, all observed adverse effects in all
      studies, toxicokinetics and toxicodynamics, exposure conditions, and more. Most
      of this information is generated in tests conducted according to internationally
      accepted guidelines. Next, the art of toxicology is to evaluate and extrapolate
      the information acquired and then to assess human and environmental health
      hazards. Thus, the validity of any hazard prediction relies both on the collected
      data and on the craftsmanship of the assessor. Unfortunately, the experts
      involved in the science of toxicology are frequently not involved in the art of
      toxicology. As a consequence, the artist who is used to his set of fine tools,
      which he bought a long time ago and with which he always managed to create the
      'sculpture' of hazard assessment, is now suddenly asked to use some new and
      rather different tools. It is understandable that this may bring about some
      opposition. In addition to these fundamental aspects, there are also political
      aspects to the issue of acceptance of alternative tests. These and other pitfalls
      have contributed to the author's opinion that progress in this respect can only
      be made by introducing the alternative tests without, at least for the time
      being, deleting the trusted existing ones.

PMID- 20693047
TI  - Preface.

PMID- 20693048
TI  - Opening address.

PMID- 20693049
TI  - Immunotoxicology: An overview.
AB  - Significant progress has occurred in the fields of basic and clinical immunology
      over the past 15 years, leading to the establishment and validation of sensitive
      methods for assessing immune system changes in humans as well as laboratory
      animals. Concern over the potential toxic effects of chemicals and certain drugs
      on the immune system prompted the application of these methods to assess the
      safety evaluation of the immune system and the establishment of the subdiscipline
      of immunotoxicology within toxicology. Methods have been selected and optimized
      for rodent testing, which have led to national and international comparative
      studies to demonstrate the reproducibility and utility of these methods for
      predicting immune system effects. Laboratories for the investigation of
      immunotoxicity have, likewise, been established during the past 10 years among
      industrial research groups for the evaluation of new chemicals and drug
      candidates. 6 years ago, Sterling Winthrop Inc. established an immunotoxicology
      laboratory dedicated to drug discovery and development effort. Experience has
      demonstrated that immunotoxicological assessment can represent an important
      aspect of any drug safety evaluation, and need not be a routine screening
      procedure, but should be driven by data suggestive of an immune system effect or
      concern over the chemical class of the agent. Assays for the evaluation are
      selected from a menu of validated methods on a case-by-case basis.
      Immunotoxicology will continue to play a more significant role in the safety and
      risk assessment process, because of the pivotal role of the immune system in host
      defence. This overview describes the structure, organization and function of the
      immune system, and experience with immunological methods development, application
      to and experience in the preclinical development of new chemical drug entities
      and in vitro applications.

PMID- 20693050
TI  - The integration of immunotoxicology in drug discovery and development:
      Investigative and in vitro possibilities.
AB  - The development of new pharmaceuticals requires a tremendous investment of time
      and resources. The early integration of investigative toxicology studies and new
      toxicological methods, such as immunotoxicological studies, into the selection of
      new drug candidates facilities compound safety evaluation, reduces risk, and
      improves development cycle time. Experience at Sterling Winthrop Inc. has led us
      to believe that immunotoxicology assessment represents an important and useful
      tool in drug discovery and development, but that it should not be applied as a
      routine screening procedure. Instead, immunotoxicity evaluation should be
      initiated as a response to knowledge about the class of drug under investigation,
      or when data from other studies suggest an effect on the immune system. Three
      examples of this approach are given and each one demonstrates the potential of in
      vitro immunotoxicology assays to reduce the time, resources and animal use
      required in the discovery and development of new drug candidates.

PMID- 20693051
TI  - The use of animal tests in risk assessment for immunotoxicology.
AB  - The design and content of a screening battery using a 'tier' approach for
      detecting potential immunotoxic compounds in mice has been described (M. I.
      Luster et al., Fundamental and Applied Toxicology 1988, 10, 2-19). The database
      generated from these studies, which consists of over 50 selected compounds, has
      been analysed in an attempt to improve future testing strategies and provide
      information to aid in developing future quantitative risk assessment for
      immunotoxicity. In a recent study it was shown that as few as two or three immune
      parameters were needed to predict immunotoxicants in mice (M. I. Luster et al.,
      Fundamental and Applied Toxicology 1992, 18, 200-210). The analyses described
      here focus on the use of this database to develop statistical models that examine
      the qualitative and quantitative relationship(s) between the immune function and
      host resistance tests. The conclusions derived from these analyses are as
      follows: (1) A good correlation exists between changes in the immune tests and
      altered host resistance, in that there were no instances where host resistance
      was altered without affecting one or more immune test(s). However, in some
      instances immune changes occurred without corresponding changes in host
      resistance. (2) No single immune test could be identified that was fully
      predictive for altered host resistance, although most assays were relatively good
      indicators (i.e. 70%). Several others, such as proliferative response to
      lipopolysaccharide and leucocyte counts, were found to be relatively poor
      indicators for host resistance changes. (3) The ability to resist infectious
      agent challenge is dependent on the degrees of immunosuppression and the quantity
      of infectious agent administered. (4) Logistic and standard regression modelling
      using one extensive chemical data set from the immunosuppressive agent,
      cyclophosphamide, indicated that most immune function-host resistance
      relationships followed linear rather than linear-quadratic (threshold-like)
      models. For most of the relationships this could not be confirmed using a large
      chemical data set and, thus, a more mechanistically based approach for modelling
      will need to be developed.

PMID- 20693052
TI  - Developments of immunotoxicology methods in the rat and applications to the study
      of environmental pollutants.
AB  - Immunotoxicity can either be expressed as immunosuppression, or as allergy or
      autoimmunity. This paper deals with immunodeficiency investigation in the rat,
      and emphasis is given to the role of histopathology. As current guidelines for
      toxicity testing pay only marginal attention to the immune system, it is evident
      that improvements have been proposed for this type of study. For evaluating the
      immune system as a possible target, we chose a tiered testing approach, in which
      basis testing was done in a subacute toxicity study in the rat following the OECD
      guideline 407. General parameters of the immune system included careful
      histopathological evaluation of lymphoid organs and tissues combined with data on
      the weights of lymphoid organs, white blood cell parameters and serum
      immunoglobulin measurements. No parameters were included in this screening that
      would compromise these toxicity experiments (e.g. immunization). The outcome of
      this first tier determined the need for additional tier-two immune function
      studies that were aimed at confirming and characterizing further immunotoxicity,
      and that comprised non-specific and specific immune responses as well as host
      resistance models to infectious diseases. The latter models are especially of
      great importance for human risk assessment. This tiered system has been validated
      by the known immunosuppressants azathioprine and cyclosporine A. Although
      conventional histopathology has shown its great value in identifying immunotoxic
      agents, morphological characterization can be improved by immunohistochemistry,
      hybrido-histochemistry (in situ hybridization) and morphometric analyses; these
      technologies are also important for the characterization of the mechanism of
      toxicant-induced immune alterations. Insight into the mechanism of action can
      also be provided by using specific animal models such as the athymic rat and the
      so-called severe combined immune deficient (scid) mouse, in which lymphoid cells
      of human and animal origin (e.g. thymus tissue) can be grafted. By comparing the
      sensitivity of the grafted tisues with immunotoxicants, data can be obtained that
      are useful for the assessment of the immunotoxicological risk for humans.
      Examples of chemicals that have been identified to be immunotoxic in the tiered
      test system in the rat are the environmental contaminants hexachlorobenzene and
      tributyltin oxide, and the results of these studies were discussed. Based on
      these data it was recommended that additional test parameters be incorporated
      into the existing OECD guideline.

PMID- 20693053
TI  - Summary of an international methods validation study, carried out in nine
      laboratories, on the immunological assessment of cyclosporin A in the Fischer 344
      rat.
AB  - In evaluating the adverse effects of chemicals on the immune response, the mouse
      has been the predominant animal species of choice. The acceptance of the mouse as
      a validated animal model has been the result, in part, of the studies conducted
      by the US National Toxicology Program (NTP). In these studies functional and host
      resistance assays were developed and validated using five compounds and four
      testing laboratories. In toxicological evaluations of drugs and chemicals, the
      rat has been the rodent species of choice of the worldwide toxicology community.
      The current study was designed to begin the validation of the rat as a model for
      immunotoxicology assessment. Nine laboratories participated in the study,
      including laboratories from Canada, France, the United States and The
      Netherlands. Before the study began a detailed protocol was prepared and standard
      operating procedures were developed. Cyclosporin A was selected as the prototype
      immunosuppressive compound, and was administered orally to male Fischer 344 rats.
      Data were collected on standardized forms and submitted to a central laboratory
      for statistical analysis. Similar dose-response trends were observed between the
      various laboratories. In the natural killer cell assay and concanavalin A mitogen
      assay similar results were observed in at least 63% of the laboratories. In the T
      dependent antibody-plaque forming cell assay, and the mixed leucocyte response,
      100% of the laboratories that conducted the assays had statistically similar
      results. The results from this study support the usefulness of the rat as a model
      species for immunotoxicity assessment and represent a beginning for international
      interlaboratory validation of immunotoxicology assays in this species.

PMID- 20693054
TI  - Immunotoxic effects of xenobiotics in humans: A review of current evidence.
AB  - Immunotoxic effects include immunosuppression and immunostimulation,
      hypersensitivity and autoimmunity. Infections and lymphoproliferative disorders
      have been associated with the use of immunosuppressive drugs, whereas infections
      have seldom been associated with chemical exposure. Fewer drugs and chemicals
      have been shown to enhance immune parameters. Clinical consequences, (i.e. flu
      like syndromes, autoimmune reactions, facilitated allergic reactions to unrelated
      antigens and impaired hepatic drug metabolism) mostly have been associated with
      recombinant cytokines. Hypersensitivity reactions have commonly been reported in
      treated patients as well as in exposed workers. Autoimmune reactions have been
      associated with only a few drugs. Overall, current evidence suggests that marked
      immune changes in humans exposed to xenobiotics can result in overt clinical
      toxicities, but it remains to be established to what extent mild to moderate
      immune changes described in animals and/or humans can result in immune-mediated
      diseases. This issue could be investigated by the follow-up of selected cohorts,
      for example patients from clinical trials, exposed workers, or inhabitants of
      heavily polluted areas, using standardized and validated immunology assays,
      together with the identification of sentinel immune diseases.

PMID- 20693055
TI  - Structure-activity relationship as a tool in contact allergy risk assessment.
AB  - About 3000 substances are known to cause contact allergy (type IV allergy). The
      possibility of predicting the sensitizing capacity of a substance by examining
      its chemical structure is discussed on the basis of the authors' own experience
      and of literature data. Since other factors also influence the allergenic
      activity of a compound, indications based on chemical considerations must be
      confirmed experimentally in animals because no in vitro methods yet exist.

PMID- 20693056
TI  - Contact hypersensitivity: Animal tests.
AB  - After reviewing general aspects and the historical development of predictive
      animal skin sensitization tests, the recommended tests of the OECD and EC are
      discussed. Background information is given on the changes that have occurred
      during the last 2 yr. Although many factors are known to influence induction and
      elicitation of contact allergy in animals, the discussion is focused on the
      choice of induction concentration and the vehicle. Differences in general
      screening strategies between Europe and the USA are considered. The paper
      concludes with a discussion about the importance of in-house validation of the
      methods used for proper prediction of the sensitizing potential of chemicals and
      with remarks on predictive in vitro tests.

PMID- 20693057
TI  - Respiratory allergy: Clinical aspects.
AB  - Human expression of pulmonary disease after exposure to chemicals is highly
      dependent on the locale and circumstances of the exposure. Most of the
      information about environmental hazards that is currently available has been
      obtained from epidemiological investigations. Chemical agents in the workplace
      have received considerable attention because the workplace is an ideal mini
      epidemiological model of air pollution. Many instances of pulmonary
      immunotoxicology are engendered by adverse reactions to drugs but of necessity
      these can only be studied on a case-by-case basis. Although the overall
      expression of pathological processes in the anatomical structures of the
      respiratory system is limited, many of the clinicopathological features induced
      by chemicals present with features that are characteristic enough to suggest that
      several stimulus-response paradigms may be applicable. In this review the
      immunotoxicological impact of chemicals on the major anatomical components of the
      lung (the conducting airways, the alveolar, interstitial and capillary
      compartments, the pleura and the pulmonary vasculature) is considered. The two
      major classes of hypersensitivity induced in humans by chemicals are those
      involving IgE humoral and cell-mediated immune responses. Although other isotypic
      antibodies (IgM, IgG, IgA), as well as complement activation, have been
      demonstrated after specific types of exposure, the role of these immune
      components in the pathogenesis of disease does not appear to be of major
      importance. Chemicals with a special propensity for IgE sensitization and effects
      on the airways include polyisocyanates, acid anhydrides and platinum salts.
      Conditions that involve the lung parenchyma are exemplified by hypersensitivity
      pneumonitis, drug-induced pneumonia and berylliosis.

PMID- 20693058
TI  - Assessment of chemicals for their potential to induce respiratory allergy in
      guinea pigs: A comparison of different routes of induction and confounding
      effects due to pulmonary hyperreactivity.
AB  - Guinea pigs were sensitized either to selected low molecular weight chemicals
      known to induce respiratory allergy in humans, trimellitic anhydride (TMA),
      toluene diisocyanate (TDI), or diphenylmethane-4,4'-diisocyanate (MDI), or to
      ovalbumin (OA) as a positive control. In most instances, sensitization was
      induced either by repeated intradermal injections or by a single brief (15-min)
      high-concentration inhalation exposure. For TMA the repeated high dose
      intradermal injection regimen was compared with a single low dose intradermal
      injection regimen. Additionally, the effectiveness of the single 15-min induction
      protocol was compared with that of five consecutive inhalation exposures each of
      3 hr/day. Animals were challenged 2-3 wk later by exposure to the substance used
      for induction, either as the free chemical or as a hapten-protein conjugate, and
      with increasing concentrations of acetylcholine (ACh). Challenge with the
      parental or conjugated hapten was used to assess compound-specific immediate
      onset respiratory hyperreactivity, while ACh challenges were used to identify non
      specific airway hyperreactivity. After intradermal sensitization with either MDI
      or TMA guinea pigs challenged with the corresponding hapten-protein conjugate
      showed a moderate incidence of immediate-type respiratory responses. However, the
      highest incidence of unequivocal allergic responses was evident from challenge
      with the hapten rather than with the protein conjugate, although these responses
      were only elicited with slightly irritant concentrations. After challenge with
      irritant concentrations of TDI, animals sensitized intradermally did not
      experience characteristic changes in respiratory patterns. On challenge with Ach
      and the TDI-protein conjugate these same animals showed an increased airway
      hyperresponsiveness although characteristic stereotypic breathing patterns, as
      observed in sensitized animals challenged with TMA, TMA-protein conjugate, or OA,
      were not detected. Comparison of the intradermal and inhalation induction
      regimens indicated that prior encounters with irritant haptens by inhalation
      reduces the concentration required to elicit airway hyperresponsiveness. This
      finding supports the conclusion that in animals sensitized and challenged by
      inhalation, irritant respiratory responses may be misconstrued as immediate-onset
      allergic responses. It appeared that the low dose single intradermal injection
      protocol is more effective in sensitizing guinea pigs than the high dose repeated
      injection protocol.

PMID- 20693059
TI  - Chemical allergy: Cellular and molecular mechanisms and novel approaches to
      predictive testing.
AB  - A wide variety of chemicals is known to cause allergy-both allergic contact
      dermatitis and respiratory hypersensitivity. Historically the species of choice
      for the predictive assessment of sensitizing potential has been the guinea pig,
      the emphasis being on measurement of allergic reactions provoked by challenge of
      previously sensitized animals. However, in parallel with enhanced understanding
      of the mechanisms through which chemical allergy is induced and regulated, there
      have emerged opportunities to define novel strategies for predictive testing.
      Much has been achieved in the mouse and this article will focus on new approaches
      to testing in this species where activity is measured as a function of events
      occurring during the induction phase of sensitization.

PMID- 20693060
TI  - MELISA-an in vitro tool for the study of metal allergy.
AB  - The sensitizing properties of metals widely used in medical and dental care have
      been studied with the help of an optimized lymphocyte proliferative assay,
      MELISA. MELISA (memory lymphocyte immuno-stimulation assay) was originally
      developed for the screening of allergenic epitopes of drugs and other chemicals
      of low molecular weight, but has recently been adapted for the study of metal
      induced sensitization. The patients studied suffered from various oral mucosal
      problems which were suspected to be caused by the release of metal ions from
      dental restorations. They were also troubled by chronic fatigue persisting over
      many years. One patient was also occupationally exposed to metals while working
      in a dental practice. Healthy subjects without any discomfort due to metal
      devices served as controls. In addition to metals used in dentistry, lymphocyte
      responses to organic mercurials used widely as preservatives in vaccines,
      eye/nose drops and contact lense fluids were studied. The results indicated that
      mercurials, as well as other metals such as gold or palladium, induce strong
      lymphocyte proliferative responses in patients with oral or systemic symptoms,
      but not in similarly exposed unaffected subjects. The results of MELISA performed
      with a pair of identical twins with chronic fatigue syndrome (CFS) indicated that
      metal-specific responses may be dependent on the genetics of the patient. Thus,
      many metals that are today accepted for use in medicine and dentistry carry a
      definite sensitizing risk for certain genetically predisposed individuals.
      Therefore, the use of these metals should be limited in the future.

PMID- 20693061
TI  - Molecular immunotoxicology testing in vitro.
AB  - Analysis of the modulation of expression of key immunoregulatory cytokines has
      significant potential for the development of in vitro immunotoxicological
      screening assays. Many techniques are available to analyse cytokine mRNA
      expression in cultures derived from specific immune cell populations; in our
      hands reverse transcription-polymerase chain reaction (RT-PCR) analysis was
      extremely sensitive but had low reproducibility, whereas dot-blot analysis gave
      acceptable levels of sensitivity and specificity and was highly reproducible.
      Certain cytokines such as IL-1 and IL-2 are pivotal to the normal development of
      an immune response. We have shown using murine in vitro systems that macrophage
      IL-1 mRNA can be induced by levels of Biostim (an immunostimulatory drug) as low
      as 10 pg/ml. We have also shown that concentrations of cyclosporin A (an
      immunosuppressive drug) down to 1 ng/ml can inhibit the expression of lymphocyte
      derived IL-2 mRNA. Other immunomodulatory compounds such as azathioprine (1
      mug/ml) and tributyltin oxide (1 nm) caused a partial inhibition of IL-2 and/or
      IL-2 receptor mRNA within rodent mixed lymphocyte cultures. Based on these
      results we are proposing a series of simple tests to predict immunomodulatory
      potential of new compounds. These techniques are equally applicable to cell
      cultures of human origin and current research in our laboratory is focused on the
      use of human peripheral blood mononuclear cells to explore the allergenic
      potential of drugs and chemicals by analysing characteristic modulation of
      patterns of normal cytokine expression.

PMID- 20693062
TI  - Skin(2TM): An in vitro model to assess cutaneous immunotoxicity.
AB  - The skin serves as a complex barrier protecting the internal environment against
      external factors (e.g. bacteria, viruses, environmental toxins and UV light). For
      the epidermis to produce the most effective toxicological, immunological and
      biochemical barrier, the major cell types of the epidermis (i.e. keratinocytes)
      and in the dermis (i.e. fibroblasts) must function together in a dynamic
      integrated fashion. Furthermore, epidermal-dermal intercellular biochemical
      signals such as interleukins (IL), cytokines and other growth factors provide the
      skin with local homoeostatic signals to ensure the skin's immune integrity in
      response to a variety of environmental insults. Other investigators have shown
      that exposure of the skin to long-wave ultraviolet light (UVA) and mid-range
      ultraviolet light (UVB) can alter epidermal immune functions, including epidermal
      cytokine (e.g. IL-1, IL-6, TNF-alpha, IL-10 and GM-CSF) levels. The studies
      reported here use a co-culture system of dermal fibroblasts and well
      differentiated epidermal layers with an attached stratum corneum to form an in
      vitro human skin analogue. Baseline endogenous levels of IL-1alpha and tumour
      necrosis factor-alpha (TNF-alpha) were detected by using commercially available
      ELISA kits. The tissue substrates were exposed to UVA/UVB light (280-400 nm). The
      UV light was administered by a Dermsol 3 mercury halide solar simulator
      configured with filters to remove energy levels below 280 nm and above 410 nm.
      Skin tissue irradiated at 4J/cm(2) revealed a significant increase in IL-1alpha
      and TNF-alpha in comparison with non-UV irradiated tissue. Additional experiments
      revealed that the topical administration of indomethacin (0.1 to 10mg/ml) to the
      skin tissue ameliorated the up-regulation of these immune cytokines following UV
      irradiation. The use of such an in vitro co-culture system may provide
      researchers with a unique method to quantify mechanistically immunotoxicological
      events in the skin after exposure to ultraviolet light.

PMID- 20693063
TI  - Activation of cultured glial cells by amitriptyline and platelet activating
      factor.
AB  - The activation of glial cells in culture by exposure to chemicals proceeds
      through two stages. The first stage appears to be an activation of
      oligodendroglial (OG) proliferation and increased activities of 2'3'-cyclic 3'
      phosphodiesterase (CNP). This stage frequently leads to a second stage, which is
      characterized by a transformation of microglia to actively phagocyting cells with
      increased 5'-nucleotidase (5'-NT) activity. Compounds of heavy metals induce OG
      proliferation and activation of CNP, but do not activate microglia. In contrast
      amitriptyline (AT) is a potent activator of microglia cells and stimulates 5'-NT.
      Exposure of the cells to platelet activated factor (PAF) or AT for 2, 5, 7 or 12
      days revealed different effects on the release of prostaglandin E(2) emphasizing
      the fact that the cells have specific receptors for PAG but not for AT.

PMID- 20693064
TI  - The value of in vitro immune function tests in the detection of potential
      immunotoxicants.
AB  - Groups of rats were treated with different doses of cyclosporin A for 28 days.
      Their spleens were then removed aseptically and used to prepare single cell
      suspensions. These were examined for their proliferative response to the T-cell
      mitogens phytohaemagglutinin (PHA) and concanavalin A (Con A), and the B-cell
      mitogen Salmonella typhimurium mitogen (STM), as well as for their ability to
      lyse (51)Cr-labelled YAC-1 cells. The spleen and other lymphoid organs were also
      examined histopathologically and differential white blood cell counts were done.
      Cells from animals treated with cyclosporin A showed a dose-dependent reduction
      in the proliferative response to Con A and, to a lesser extent, to PHA, but not
      to STM. In contrast, natural killer activity, measured by YAC-1 cell lysis,
      increased with greater cyclosporin A dosage. Histological examination of spleen
      and lymph nodes also revealed changes at all doses, particularly in T-dependent
      areas. White blood cell counts were largely unaffected. Thus, while in vitro
      immune function tests did not prove to be necessary for the identification of
      potential immunotoxicity in this model, they provided valuable information about
      possible mechanisms and guidance for further investigations.

PMID- 20693065
TI  - Influence of organophosphorus compounds on different cellular immune functions in
      vitro.
AB  - The effects of two organophosphorus compounds (OP) triphenyl phosphate (TPP) and
      triphenylphosphine oxide (TPPO) on different immune functions in vitro were
      investigated using an economical multiple endpoint approach. The test battery was
      designed as follows: immunocompetent cells (peritoneal cells and splenocytes)
      were isolated from female C57B1 mice and treated in vitro for 1 hr with the test
      article. Then the cells were washed and assessed for the following immune
      functions: Fc-receptor-dependent phagocytosis and lipopolysaccharide-induced
      release of a cytolytic protein (tumour necrosis factor, TNF) of thioglycollate
      elicited peritoneal macrophages; natural killer (NK) cell activity, blastogenesis
      (T and B lymphocytes), and antibody synthesis (B lymphocytes) of spleen-cell
      suspensions. As an additional parameter the survival of the cells was determined
      routinely after treatment during all assays. No substantial effect on macrophage
      phagocytotic activity was observed after TPP or TPPO treatment. TPP led to a
      concentration-dependent suppression of macrophage TNF activity as well as NK
      activity of spleen cells. In addition, a slight reduction of B-lymphocyte
      antibody synthesis was obtained. TPPO treatment revealed a modulation of TNF
      activity of macrophages in a complex, non-concentration-related manner. A
      concentration-related suppression of spleen cell NK activity was observed after
      TPPO treatment. In summary, TPP and TPPO were found to be immunomodulating agents
      eliciting adverse effects predominantly towards cells of the innate immunity. The
      functions of T and B lymphocytes, referred to as adaptive immunity, were not
      substantially impaired. Our results indicate that the in vitro test battery
      described may be a suitable tool for the screening of OP-mediating
      immunotoxicity.

PMID- 20693066
TI  - PCB congeners and the murine immune system: The capacity of isolated congeners to
      decrease spleen specific antibody forming cell numbers varies with the toxic
      equivalence factors of the congeners.
AB  - Polychlorinated biphenyl (PCB) congeners 77 (3,3',4,4'-tetrachlorinated biphenyl)
      and 118 (2,3',4,4',5-pentachlorinated biphenyl) were given by gavage as a single
      dose to female C57BL/6J mice. The dose levels tested were 25 and 100 mumol/kg
      body weight for PCB-77, and 250 and 800 mumol/kg for PCB-118. 2 days after
      dosing, the mice were either immunized with sheep red blood cells (SRBC) or they
      were killed and their livers were removed for determination of ethoxyresorufin-O
      deethylase (EROD) activity, and their spleens were removed for assays of natural
      killer (NK) cells and mitogen stimulation assays. The immunized mice were killed
      4 days after immunization, and their spleens were removed for determination of
      the number of plaque forming cells. Both congeners induced a reduction in anti
      SRBC forming cells and an increase in liver microsomal EROD activity, their
      relative potencies being of the same order of magnitude as reported for their
      general toxicity. No effect was observed on NK cell activity or on the response
      to mitogens in vitro.

PMID- 20693067
TI  - Effects of chlorinated solvents on the natural lymphocytotoxic activities of
      human liver immune cells.
AB  - Inhibition of the natural immune system may be involved in the liver cancer
      caused by some non-genotoxic chemicals when they are administered at high doses
      to certain strains of animals. Previous studies have shown that some chlorinated
      solvents inhibit liver natural immune function in rodents. In this preliminary
      study, the effects of in vitro exposure to three commonly used chlorinated
      solvents were determined on three tumoricidal activities expressed by isolated
      human liver immune cells-natural killer (NK), natural cytotoxic (NC) and natural
      P815 killer (NPK) (Wright and Stacey, 1991) cell activities. The NK, NC and NPK
      cell activities of immune cells isolated from three human livers were 115, 45 and
      53 lytic units (LU(20%)/10(6) effector cells), respectively. In vitro exposure to
      trichloroethylene (TRI) inhibited all three natural immune activities, and the
      ranking of sensitivity was NPK NC NK. Tetrachloroethylene (TET) inhibited NC and
      NPK cell activities, but had little effect on NK cell activity. 1,1,1
      Trichloroethane (TCE) had little or no effect on the three tumoricidal activities
      examined. Overall, these data show clear similarities to the results obtained in
      vitro using cells from experimental animals.

PMID- 20693068
TI  - Lymphocyte proliferative response to drugs: Analysis of the value of a 24-well
      lymphocyte culture system.
AB  - The aim of this study was to analyse the value of a 24-well lymphocyte culture
      system in the detection of lymphocyte sensitization to drugs in 19 patients with
      drug-induced liver injury and 19 healthy controls. Lymphocytes responses to drugs
      under suspicion were assessed in vitro by [(3)H]thymidine incorporation in the
      lymphocytes. The responses observed in cultures with and without the drug were
      compared using Student's t-test for the analysis of significance of differences.
      Data were also analysed to calculate estimates of the frequency of drug-specific
      T cells by Poisson sampling statistics. The mean and the standard deviation (SD)
      of the cpm in the 24-well 'negative' cultures (without drug) were determined. A
      cut-off for negative results, corresponding to the mean plus 2SD, was
      established. Negative wells (lower than the cut-off) were counted in the
      'positive' cultures (cultures with drug) and the Poisson mean (PM) was determined
      as follows: PM = natural logarithm of number of wells tested/number of negative
      wells. The results were compared with those observed using a triplicate culture
      system in the same patients. In 14 out of 19 cases studied, significant
      differences between the means of lymphocyte cultures with and without drug were
      observed, whereas in the triplicate system, reactivity was found only for nine
      cases. In all cases in which more than one drug was tested, lymphocyte
      sensitization was detected to only one drug. No positive cases were detected in
      the group of healthy controls. The estimated precursor frequencies varied between
      0.3 and 1.3 per 100,000 cells. The results represent further evidence that drug
      specific T cells exist in the peripheral blood of patients with drug-induced
      liver injury and justifies a more extensive analysis of the value of the 24-well
      culture system from a diagnostic point of view.

PMID- 20693069
TI  - Prediction of drug-induced immediate hypersensitivity in guinea pigs.
AB  - This study was undertaken to evaluate an assay to assess the risk for drug
      induced immediate hypersensitivity reactions. Groups of five to 10 guinea-pigs
      were given six ip injections of the test compound on days 1, 3, 5, 8, 10 and 12.
      Aluminium hydroxide was also given in the first injection. At day 33, the animals
      were given an iv injection of the test compound and the response was recorded by
      grading the severity of clinical symptoms. Cutaneous passive anaphylaxis was also
      evaluated in six naive guinea pigs using Evans blue and sera collected from
      treated animals on day 26. A panel of six positive model compounds (ovalbumin,
      aprotinin, chymopapain, tetracosactide, cyanocobalamin and procaine), and the
      negative compound Ribomunyl were tested. Positive systemic and/or cutaneous
      anaphylactic responses were observed with ovalbumin, aprotinin, chymopapain and
      tetracosactide whereas no responses were noted with cyanocobalamin, procaine and
      Ribomunyl. Our results suggest that this protocol can help differentiate positive
      model compounds (known to induce reactions in man) from negative model compounds,
      provided that their molecular weight is large enough, but that it is not
      applicable to substances of low molecular weight.

PMID- 20693070
TI  - Specific human IgE response after immunization with birch pollen in scid mice
      transplanted with human peripheral blood mononuclear cells-A model for human
      allergy?
AB  - C.B-17 scid mice were transplanted ip with human peripheral blood mononuclear
      cells. Some transplanted mice were immunized ip with birch pollen. Levels of
      total and birch pollen-specific human IgE were measured in serum. Low levels of
      total human IgE were detected after 9 days. 20 days after transplantation 12 out
      of 12 mice transplanted with cells from a birch pollen allergic donor showed
      higher but variable levels of total human IgE, and a low level of birch pollen
      specific IgE was detected in one mouse that had not been immunized. Immunization
      with birch pollen did not influence the level of total human IgE. In a different
      experiment, mice transplanted with cells from a donor with a high level of total
      IgE, but without birch pollen allergy, developed high levels of total IgE 49 days
      after transplantation, whereas no birch pollen specific IgE was found (two
      immunized, two non-immunized mice). In contrast, two of four mice given cells
      from two donors with birch pollen allergy, but with lower levels of total IgE,
      produced birch pollen-specific IgE after immunization. Thus, measurable levels of
      total human IgE were spontaneously produced in most scid mice transplanted with
      human peripheral blood mononuclear cells. Detectable levels of birch pollen
      specific human IgE appeared to be produced in occasional non-immunized scid mice
      transplanted with cells from allergic donors. In mice given cells from some
      allergic donors, half the mice produced human birch pollen specific IgE after
      immunization.

PMID- 20693071
TI  - An expert system rulebase for identifying contact allergens.
AB  - There are currently no in vitro methods suitable for the prospective
      identification of skin sensitizers (contact allergens). Knowledge relating
      chemical structure to toxicity can be programmed into expert systems. An
      historical database, containing results of 294 defined single substances tested
      in the guinea pig maximization test (GPMT) carried out according to a single
      protocol, has been used to derive a set of structural alerts for skin
      sensitization. Where possible, the approach used was to group the substances
      according to their most likely mechanism of reaction with skin proteins. Where no
      mechanism could be identified, structural alerts were derived empirically for
      groups of molecules with similar chemical functionality. This process has
      currently resulted in the production of 40 structure-activity rules which have
      been incorporated into the expert system DEREK. This system forms an integral
      part of a strategic approach to the identification of contact allergens.

PMID- 20693072
TI  - Delayed developmental immunotoxicity of prenatal benzodiazepines.
AB  - Treatment of pregnant rats with low doses of classical benzodiazepines (BDZ, e.g.
      1.25 mg diazepam/kg body weight) or a peripheral type BDZ receptor (PBR) agonist
      between gestational days 14 and 20 has been shown to result in a long-lasting
      depression of cellular and humoral immune responses in the offspring.
      Considerable alterations in mitogen-stimulated cytokine production in rats
      exposed to diazepam prenatally have now been observed: TNF-alpha liberation by
      splenocytes of diazepam-exposed rats was reduced at 2 wk of age and increased
      above control values at 8 wk, and interleukin (IL)-6 was depressed in the
      offspring at 2 and 8 wk of age. IL-1 was diminished during post-weaning and adult
      periods in male offspring but only in adult life in female offspring. In
      contrast, T-cell derived IL-2 was decreased during the postnatal period and
      normalized in adulthood. Prostaglandin E(2) (PGE(2)), which is known to down
      regulate tumour necrosis factor-alpha (TNF-alpha) was increased and interferon
      gamma (IFN-gamma), which stimulates TNF-alpha release, was depressed in 2-wk-old
      offspring that had been treated prenatally. Release of PGE(2) and IFN-gamma was
      still altered in young adulthood. While the initial action on the foetal immune
      system remains unknown, an interaction of the drugs with the PBR is suggested by
      the effectiveness of the PBR agonist and by altered characteristics of PBR (i.e.
      a decreased B(max) of [(3)H]PK 11195 binding to macrophage membranes of 8-wk-old
      offspring and an increased Kd of spleen cell membranes of 2-wk-old offspring).

PMID- 20693073
TI  - Workshop: Immunotoxicology and in vitro possibilities.

PMID- 20693074
TI  - In vitro cytotoxicity of the chlorinated naphthoquinone dichlone to human
      endothelial ECV304 cells.
AB  - The cytotoxicity of the pro-oxidant fungicide dichlone (2,3-dichloro-1,4
      naphthoquinone), to the human endothelial cell line, ECV304, was evaluated. The
      sensitivity of these cells to dichlone was intermediate between that of human
      hepatoblastoma HepG2 cells (least sensitive) and that of human GMO5757
      fibroblasts. The midpoint cytotoxicity values for a 24-hr exposure to dichlone
      was about 0.02 mm when evaluated with the neutral red, acid phosphatase, and XTT
      tetrazolium assays. Lactic acid dehydrogenase leakage, after a 4-hr exposure,
      occurred initially at 0.05 mm dichlone. As with other naphthoquinones, cellular
      metabolism of dichlone presumably could proceed either by a one- or a two
      electron reduction reaction. The enhancement of potency of dichlone towards
      ECV304 cells pretreated with the glutathione-depleting agents, dl-buthionine
      [S,R]-sulfoximine, 1-chloro-2,4-dinitrobenzene, and 1,3-bis(chloroethyl)-1
      nitrosourea; the reduction in potency of dichlone to cells pretreated with (-)-2
      oxo-4-thiazolidine carboxylic acid; the decrease in intracellular glutathione on
      exposure to dichlone; the subtle damage to the plasma membrane of dichlone
      treated cells (as detected by the leakage of lactate dehydrogenase from these
      cells); and the lack of potentiation of dichlone toxicity by pretreatment with
      dicoumarol, are all consistent with the one-electron reduction reaction as the
      dominant pathway and with the subsequent generation of reactive oxygen molecules.
      The ECV304 cell line proved to be a useful research tool to study cytotoxic
      injury to endothelial cells.

PMID- 20693075
TI  - Cytotoxicity and lamellar body induction potential of a racemic benzamide
      antiarrhythmic compound and enantiomers in cultured rat hepatocytes.
AB  - A wide variety of cationic amphiphilic compounds induce cytoplasmic lamellar
      bodies, accompanied by phospholipidosis and often coincidental with toxicity. The
      in vitro cytotoxic and lamellar body-inducing potentials of a racemic cationic
      amphiphilic benzamide antiarrhythmic compound and its trans-enantiomers were
      examined. Cultured rat hepatocytes were treated for 24 hr with the racemate and
      (+) and (-) trans-enantiomers in increasing concentrations to 1.0 mm. All
      compounds produced significant cytotoxicity at concentrations of 250 mum and
      greater, as assessed by lactate dehydrogenase release, but the (-) enantiomer was
      less cytotoxic than the racemate and (+) enantiomer at 500 mum. Electron
      microscopy revealed significant formation of lamellar bodies in all treated
      cultures at concentrations of 100 mum and higher for all compounds, with the (-)
      enantiomer producing significantly fewer lamellar bodies than the (+) enantiomer
      or racemic mixture. Acid phosphatase cytochemistry indicated that most, but not
      all, lamellar bodies were lysosomes. Fluorescence distributional studies with a
      phospholipid analogue, 1-acyl-2-[12-(7-nitro-2-1-,3-benzoxadiazol-4
      yl)amino]dodecanoyl phosphatidylcholine, in living cells confirmed drug-induced
      cytoplasmic vacuoles to be formed from labelled plasma membrane at racemate drug
      concentrations as low as 10 mum, and suggested that lamellar body formation
      proceeds by a dynamic process involving the plasma membrane. These data indicate
      stereo-selective lamellar body-and cytotoxicity-inducing potentials between
      enantiomers, and that these are dissociable processes.

PMID- 20693076
TI  - Ex vivo study on ATPase activities of rabbit renal proximal tubules as a
      predictive model for nephrotoxicity: Comparison with an in vitro study on a new
      cephalosporin (cefpirome).
AB  - An ex vivo study on adenosine triphosphatase (ATPase) activities of rabbit renal
      proximal tubules was conducted with a new cephalosporin, cefpirome (HR 810), a
      positive control, cephaloridine, and a reference third-generation cephalosporin,
      cefotaxime. Compared with controls, CPH caused a significant time-dependent
      decrease in ATPase activities [12%, 2 hr after treatment (P < 0.01) and 75%, 48
      hr after treatment (P < 0.001)]. This decrease was accompanied by a significant
      loss in the energy charge of the adenylate pool [27%, 2 hr after treatment (P <
      0.001)]. Neither cefotaxime nor cefpirome caused such decreases. The results
      confirmed those of a previously published in vitro study. The advantages and
      disadvantages of these two experimental procedures as predictive models for
      nephrotoxicity are discussed.

PMID- 20693077
TI  - Embryotoxic potency of 2,4,5-trichlorophenoxyacetic acid on sea urchin eggs:
      Association with calcium homoeostasis.
AB  - The effect of 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), a polychlorinated
      herbicide, on the early development of sea urchin eggs and on Ca(2+) permeability
      was investigated. Concentrations lower than 5 x 10(-4)m delayed the first
      cleavages and produced a teratogenic effect characterized by a large spectrum of
      structural malformations at the pluteus stage. The cleaving stage (pre-hatching)
      was the period most sensitive to the compound. Upper concentrations caused a
      stepwise dose-dependent lethality associated with arrest of cleavage. 2,4,5-T
      increased plasmalemma Ca(2+) permeability of unfertilized eggs by opening voltage
      dependent Ca(2+) channels; verapamil (10(-4)m) and nifedipine (10(-4)m) abolished
      this effect. Ca(2+) permeability was also increased by 2,4,5-T after
      fertilization of the eggs. ATP-dependent intracellular sequestration of Ca(2+),
      measured in isolated cortices, was inhibited by 2,4,5-T. Ca(2+) movement was
      affected over a range of concentrations similar to those producing embryonic
      abnormalities and lethality. The results suggest that the teratogenic potency of
      2,4,5-T is associated with delay in first cleavages and alterations in Ca(2+)
      homoeostasis.

PMID- 20693078
TI  - Cytotoxicity of chlorophenols to goldfish GFS cells with the MTT and LDH assays.
AB  - The cytotoxicity of phenol and 14 chlorophenols (CPs) were examined in goldfish
      scale (GFS) cells, a fibroblastic cell line derived from goldfish scales. MTT
      reduction and intracellular LDH activities were examined as cytotoxicity
      indicators. Cell densities at inoculation were 1.0 x 10(5) cells/ml in the MTT
      assay and 0.5 x 10(5) or 0.1 x 10(5) cells/ml in the LDH assay. No change in the
      midpoint cytotoxicity concentration (IC(50)) was observed in either assay at the
      same order of cell density (0.5-1.0 x 10(5) cells/ml). However, at low chemical
      concentrations, the LDH assay was more sensitive than the MTT assay. In addition,
      for many CPs, the LDH assay at 0.1 x 10(5) cells/ml was more sensitive than the
      MTT and LDH assays at the higher cell density levels. The correlation
      coefficients (r) for all IC(50) determinations were greater than 0.97. Good
      correlations between these assays and the neutral red (NR) assay were also
      observed (r > 0.97). The 1-octanol/water partition coefficient (log P) gave good
      correlation coefficients (r > 0.90) with IC(50) values of both the MTT and LDH
      assays in simple linear regression analyses. The study demonstrates that both the
      MTT and LDH cytotoxicity assays with GFS cells, together with the NR assay, can
      be applied to screen the acute toxicities of chemicals.

PMID- 20693079
TI  - Cytotoxicity tests on eye drop preparations by LDH release assay in human
      cultured cell lines.
AB  - Using a simple protocol developed for sensitive assays of lactate dehydrogenase
      (LDH) release by cultured human cell lines, cytotoxicity was observed in seven of
      nine commercially available eye drop preparations tested using a human lung
      carcinoma cell line, SQ-5, and in eight of nine preparations using a human
      leukaemia cell line, HL60. However, six of nine preparations were found to be
      cytotoxic to SQ-5 using the neutral red uptake assay. One of these eye drop
      preparations induced release of LDH within 1 min from SQ-5 cells and within 5 min
      from HL60 cells. This preparation also induced a three-fold increase in LDH
      activity in tears, 10 sec after its application to human eyes, suggesting that
      cells in contact with the tears were injured by the eye drops in vivo. An eye
      drop preparation that had no detectable cytotoxicity in vitro caused no change of
      LDH activity in human tears. LDH release assay has therefore been shown to be a
      useful method for detecting a direct relationship between in vitro cytotoxicity
      and weak in situ cytotoxicity to human eyes.

PMID- 20693080
TI  - Embryopathic effects of diazoxide and the reduction of sulfonylurea-induced
      dysmorphogenesis in vitro.
AB  - Diazoxide is a benzothiadiazine used in oral and intravenous preparations to
      treat hypertension and hypoglycaemia, but its effect on embryonic development has
      not been well studied. Previous in vivo work has suggested placental transfer and
      teratogenicity of diazoxide in humans and laboratory animals, but this study
      represents the first in vitro investigation of the effect of diazoxide on the
      embryo. The in vitro method of whole-embryo culture was used to expose mouse
      embryos to specific levels of diazoxide (0-200 mug/ml) during organogenesis at
      well-defined (4-6 and 20-25 somite) stages of development. In addition, the
      combined effect of diazoxide [ATP-sensitive K(+) (K(ATP)) channel opener] and the
      sulfonylurea oral hypoglycaemic agent chlorpropamide (K(ATP) channel blocker),
      was evaluated in vitro in embryos with 4-6 somites. Diazoxide produced
      malformations and growth retardation in mouse embryos exposed to 100 mug/ml or
      more for 24 hr in vitro at both stages of organogenesis. In addition, a
      subteratogenic concentration of diazoxide (25 mug/ml) reduced the embryopathic
      effects of chlorpropamide (130 mug/ml) in embryos with 4-6 somites. A potential
      mechanism for these effects involves K(ATP) channels.

PMID- 20693081
TI  - Phenobarbital pretreatment in vivo and in vitro and the effect of hepatotoxicity
      of d-galactosamine in rat hepatocytes in culture.
AB  - Galactosamine (GalN) is a known hepatotoxic compound, acting by depletion of
      uracil nucleotides. The relation between an active cytochrome P-450 system (CYP)
      and the hepatotoxicity of GalN was studied in rat hepatocytes that were
      pretreated with phenobarbital (PB) in vivo or in vitro. A 24-hr in vitro
      pretreatment of cultured hepatocytes with PB resulted in a significant decrease
      in GalN toxicity as measured by lactate dehydrogenase (LDH) leakage. Furthermore,
      GalN treatment resulted in an increase in the activity of the PB-induced forms of
      CYP (namely CYP 2B1/2) as measured by 7-pentoxyresorufin O-depentylase (PROD)
      activity. This increase was not found after GalN treatment of microsomes. GalN
      had no effect on the concentration of the apoenzymes. GalN administration to
      hepatocytes of in vivo PB-pretreated rats resulted in a similar effect of GalN on
      the activity of the CYP enzymes but PB in vivo had no effect on GalN toxicity.
      These results suggest that GalN treatment may result in a significant increase in
      the specific activity of CYP 2B1/2 enzymes (PROD), without an obvious increase in
      the amount of PB-induced apoenzymes. This phenomenon was measurable only in
      intact cells. No direct relation is assumed between the activity of the CYP
      apoenzymes and the decrease in GalN toxicity after PB treatment. The toxicity of
      Galn was inhibited by PB treatment in vitro.

PMID- 20693082
TI  - Investigations into the mechanisms of carcinogen-induced nuclear enlargement in
      HeLa S3 cells in vitro.
AB  - Carcinogen-induced nuclear enlargement has been reported both in vitro and in
      vivo, but the mechanism, and whether it is causally related to carcinogenesis,
      has not yet been established. This study was designed to investigate the role of
      increased DNA content, such as might occur in polyploidy, in induction of nuclear
      enlargement. The effects of two genotoxic carcinogens, N-methyl-N-nitrosourea and
      adriamycin, were compared with the effects induced by diethylstilboestrol, which
      is arguably a non-genotoxic carcinogen but is known to induce polyploidy. HeLa S3
      cells were used as the model system for comparison with previous studies. N
      methyl-N-nitrosourea and adriamycin both induced a concentration-related increase
      in nuclear size 24 to 72 hr after a 30 min pulse-treatment. This was accompanied
      by an increase in the proportions of cells in the G(2) + M stage of the cell
      cycle, possibly due to a G(2) block. There was some evidence of polyploidy with
      adriamycin but not with N-methyl-N-nitrosourea. The distributions of nuclear
      areas indicated that increases in ploidy contributed to, but did not totally
      account for, the nuclear enlargement. In contrast, diethylstilboestrol increased
      the range of nuclear areas and DNA content, to both less than and greater than
      that of control cells, but only after a prolonged exposure period of 48 hr. These
      data were consistent with diethylstilboestrol inducing spindle damage. These
      results demonstrate that carcinogen-induced nuclear enlargement is only partially
      explained by increased nuclear DNA content, and that certain classes of non
      genotoxic carcinogen may produce a completely different pattern to that from
      genotoxic carcinogens.

PMID- 20693083
TI  - Assessment of cell-specific cytotoxic responses of the kidney to selected
      aromatic hydrocarbons.
AB  - The present studies were conducted to assess cell-specific cytotoxic responses of
      the kidney to selected aromatic hydrocarbons (AHs) using in vitro culture systems
      of glomerular mesangial cells and cortical tubular epithelial cells. Primary
      cultures of glomerular mesangial cells or cortical tubular epithelial cells were
      treated for 24 hr with naphthalene (NAPH, 0.1-1000 mum), 2-methylnaphthalene (2
      MNAPH, 0.1-1000 mum), benzo[a]pyrene (B[a]P, 0.3-300 mum), pentachlorophenol
      (PCP, 0.1-1000 mum), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, 0.001-1 nm) or
      2,3,7,8-tetrachlorodibenzofuran (TCDF, 0.005-5 nm). [(3)H]Thymidine incorporation
      into DNA, cellular potassium content, and lactate dehydrogenase (LDH) leakage
      were used as indices of cytotoxicity. Glomerular mesangial cells exposed to NAPH
      or 2-MNAPH (0.1-1000 mum) exhibited [(3)H]thymidine incorporation profiles
      similar to those of the vehicle controls, whereas B[a]P at all concentrations and
      PCP at 1000 mum decreased [(3)H]thymidine incorporation in comparison with the
      controls. TCDD and TCDF increased [(3)H]thymidine incorporation relative to
      controls at 0.1 nm and 0.5 nm, respectively. Glomerular mesangial cells treated
      with NAPH or PCP exhibited decreased cellular potassium content and increased LDH
      leakage only at the 1000 mum concentration. In tubular epithelial cells,
      treatment with NAPH (10 or 1000 mum), 2-MNAPH (10 or 1000 mum), B[a]P (300 mum),
      and PCP (10 or 1000 mum) induced concentration-dependent decreases in
      [(3)H]thymidine incorporation relative to controls. In contrast, exposure of
      tubular epithelial cells to TCDD or TCDF did not modulate [(3)H]thymidine
      incorporation at any of the concentrations tested. A modest decrease in cellular
      potassium content and an increase in LDH leakage was observed at the 1000 mum
      concentration of PCP in tubular epithelial cells. On the basis of these data, we
      conclude that renal glomerular mesangial cells and tubular epithelial cells
      exhibit differential cytotoxic response profiles to AHs.

PMID- 20693084
TI  - Xenobiotic metabolizing enzyme activities in isolated and cryopreserved human
      liver parenchymal cells.
AB  - Liver parenchymal cells (hepatocytes) of human organ donors were isolated using a
      two-step collagenase perfusion technique. The average viability of the freshly
      isolated liver parenchymal cells, as judged by trypan blue exclusion, was 82% (SD
      = 7%; n = 6). The inter-individual differences in the determined enzyme
      activities were less than a factor of 7.5, despite the different sexes and ages
      of the donors. Freshly isolated parenchymal cells (PC) were cryopreserved using a
      computer-controlled freezing protocol. After thawing, cryopreserved cells had a
      mean viability of 57% (SD = 18%; n = 6). The activities of xenobiotic
      metabolizing enzymes in freshly isolated and cryopreserved cells were compared
      using PC from two donors. The enzyme activities of phenol sulfotransferase, 1
      naphthol UDP-glucuronosyltransferase and microsomal epoxide hydrolase were well
      maintained after thawing (87-117% of activities in freshly isolated cells),
      whereas the activities of glutathione S-transferase, monitored with the broad
      spectrum substrate 1-chloro-2,4-dinitrobenzene, and the major broad spectrum
      cytosolic epoxide hydrolase were moderately but markedly reduced after
      cryopreservation (34-64% and 45-89% of levels in fresh cells, respectively). The
      decrease of both activities was dependent on the viability after thawing. When
      cryopreserved cells were purified by a Percoll centrifugation after thawing, the
      viability was increased from 62 to 92% for cells from one of the donors and from
      88 to 98% for PC for the other donor. Subsequently the activity of glutathione S
      transferase in Percoll-purified PC from the two donors was increased to 71 and
      96% of levels in freshly isolated cells. It is concluded that the use of
      cryopreserved liver parenchymal cells of humans and other species represents a
      valuable tool in predicting which animal species best represents humans in
      hepatic metabolism and therefore should be the preferred species for
      investigations of metabolism and metabolism-dependent toxicities.

PMID- 20693085
TI  - Quantification of CYP1A1 and 2B1/2 in rat hepatocytes cultured in microwells by
      immunological methods.
AB  - The quantification of P-450 enzymes (CYP proteins) is of great relevance for drug
      metabolism and toxicity studies. Their measurement in cultured cells requires a
      sufficient amount of cellular protein to isolate a minimal amount of functional
      microsomes. The difficulties in obtaining microsomes from a small number of
      cultured hepatocytes make it necessary to use more sensitive methods.
      Immunological methods can overcome such drawbacks. However, their use is
      prevented by the fact that P-450 enzymes are membrane proteins that require the
      use of detergents for adequate solubilization which, in turn, can interfere with
      the antigen-antibody recognition. A sensitive immunoassay (competitive indirect
      ELISA) was developed which allowed quantification of CYP1A1 and CYP2B1/2 in small
      culture plates with a reduced number of cells. The main advantages of this ELISA
      were: (1) precise measurement of both proteins over a wide range of antigen
      concentration (10-10,000 fmol CYP proteins); (2) minimal sample handling allowing
      reproducible titrations in small number of cells; (3) minimization of
      interference by detergents; (4) an excellent correlation (r = 0.96-0.98) between
      the immunologically determined CYP1A1 and CYP2B1/2, and the activities of
      ethoxyresorufin-O-deethylase (EROD) and pentoxyresorufin-O-depentylase (PROD),
      respectively. This assay allowed a precise monitoring of the expression of CYP
      proteins in cultured cells. Upon incubation of hepatocytes with 3
      methylcholanthrene the levels of immunoreactive CYP1A1 and CYP2B1/2 were
      paralleled by an increase of the enzymatic activities of EROD and PROD,
      respectively. In cultured rat hepatocytes treated with phenobarbital, significant
      EROD activity was detected in the absence of immunoreactive CYP1A1 induction.
      Analogously, there was a dissimilarity between enzymatic activity and protein
      levels in ageing cultures: the decrease of PROD activity preceded by several
      hours that of the immunoreactive CYP2B1/2, which emphasizes the need to determine
      individual CYPs, in addition to their enzymatic activities.

PMID- 20693086
TI  - Verification of a mathematical method for the estimation of the acute ingestion
      hazard of detergent preparations.
AB  - The hazard posed by the accidental ingestion of preparations has traditionally
      been assessed either by carrying out an acute oral toxicity test on animals or by
      extrapolation from data on tested preparations of similar composition. The EC
      Directive on the Classification, Packaging and Labelling of Dangerous
      Preparations (CPL Directive; EEC, 1988) requires that a preparation is classified
      by a mathematical procedure known as the Conventional Method. This method can
      result in preparations being classified as "Harmful" by ingestion even though
      they are not considered to be a significant ingestion hazard on the basis of the
      results of tests on similar preparations or surveys of accidents with marketed
      products. This paper proposes an alternative mathematical method, the
      Proportionality Method, for assessing the acute ingestion hazard of detergent
      preparations. Based on historical animal test data, the Proportionality Method
      predicted acute ingestion hazard classification better than the Conventional
      Method. The number of preparations which would be labelled unnecessarily is
      reduced, while the safety to the consumer is not compromised by
      underclassification. The Proportionality Method could reduce the number of animal
      tests needed to overturn incorrect classifications obtained by the Conventional
      Method by providing a more rational estimate of the acute oral ingestion hazard.

PMID- 20693087
TI  - Effects of vitamin C and PCB metabolites on the inhibition of aryl hydrocarbon
      hydroxylase and suppression of mutagenicity of benzo[a]pyrene.
AB  - The reverse mutations of Salmonella typhimurium TA98 and TA100 induced by
      benzo[a]pyrene (BP) were suppressed by about 90% by vitamin C (1500 mug/plate).
      Of 11 polychlorinated biphenyl (PCB) metabolites tested (150 mug/plate), 3
      methylsulfonyl-3',4,4',5-tetrachlorobiphenyl (3-MSF-3',4,4',5-tetraCB), 3-MSF
      3',4,4',5,5'-pentaCB and 4-MSF-3,3',4',5,5'-pentaCB also strongly suppressed the
      mutagenicity of BP. In addition, vitamin C reduced the activity of aryl
      hydrocarbon hydroxylase (AHH) in microsomes from aromatic hydrocarbon-responsive
      (Ah-responsive) and Ah-non-responsive strains of mice that had been pretreated
      with olive oil (vehicle), 3-methylcholanthrene or 2,3,7,8-tetrachlorodibenzo-p
      dioxin. Vitamin C affected the AHH activities in the same way in both strains of
      mice, but the extent of inhibition was somewhat smaller in the Ah-responsive
      strain than in the Ah-non-responsive strain. In contrast, 3-MSF-3',4,4',5
      tetraCB, one of the most potent AHH inhibitors among 11 PCB metabolites showed
      various inhibitory effects depending upon the origin of the microsomes. It is
      suggested that vitamin C is directly bound to the substrate BP, to cytochrome P
      450 itself or to the substrate-enzyme complex, thus lowering the rate of AHH
      reaction, and that the mechanisms of inhibition of AHH and suppression of
      mutagenicity by vitamin C are different from those of PCB metabolites.

PMID- 20693088
TI  - Spermatocyte toxicity of 2-methoxyethanol in vivo and in vitro: Requirement for
      an intact seminiferous tubule structure for germ cell degeneration.
AB  - Cultures of isolated testicular cells are widely used for evaluating mechanisms
      of action of direct-acting testicular toxicants. However, for testicular cells,
      the expression of toxicity in vitro is frequently different from that found in
      vivo. 2-Methoxyethanol (ME) produces testicular lesions in rats which are
      characterized by pachytene spermatocyte degeneration 24 hr after dosing. As part
      of a study to evaluate mechanisms of male germ cell toxicants, we compared the
      morphological aspects of spermatocyte toxicity after in vivo exposure to ME with
      those found in various testicular cell culture systems after in vitro exposure to
      the active ME metabolite, 2-methoxyacetic acid (MAA). Immature rats were used
      because they respond to in vivo ME treatment in the same way as adults, but their
      testes are relatively enriched in pachytene spermatocytes. 24-day-old rats were
      given a single dose of 250 mg ME/kg body weight by gavage and the testes were
      evaluated 24 hr after dosing. In vitro, cultured seminiferous tubules, Sertoli
      germ cell co-cultures, and enriched mixed germ cells, all prepared from 24-day
      old rats, were evaluated after 24-hr in vitro exposure to 5 mm MAA (a level of
      MAA found after ME exposure in vivo). Testes from ME-exposed rats showed the
      expected pachytene spermatocyte degeneration 24 hr after dosing. Similar changes
      were observed in cultured seminiferous tubules after 24 hr of exposure to MAA in
      vitro. However, without the intact seminiferous tubule structure in vitro, the
      expression of MAA spermatocyte toxicity was different. In conventional Sertoli
      germ cell co-cultures, spermatocyte detachment from the Sertoli cell monolayer
      occurred as expected, although no significant morphological degeneration was
      observed in these detached germ cells. Similarly, no increase in degenerating
      spermatocytes was noted in isolated enriched mixed germ cells after in vitro MAA
      exposure. Instead, toxicity in these germ cell fractions was expressed only by
      increased uptake of trypan blue dye, revealing an increase in plasma membrane
      permeability. In summary, this in vivo/in vitro comparison of the spermatocyte
      toxicity of ME/MAA showed that the expression of toxicity is different in the
      different culture architectures and that an intact seminiferous tubule structure
      is required for full expression of the morphological degeneration produced by
      ME/MAA, and suggests the usefulness of culture seminiferous tubules in future
      mechanistic studies.

PMID- 20693089
TI  - Mechanism of cisplatin nephrotoxicity in rat renal proximal tubule suspensions.
AB  - The effect of the nephrotoxic antineoplastic agent, cisplatin, on isolated rat
      renal proximal tubule suspensions was examined. [(195m)Pt]Cisplatin (31.7 mum)
      uptake was progressive over a 5-hr incubation period to a maximum value of 8.39
      nmol/mg protein. The addition of the metabolic inhibitors KCN and iodoacetic acid
      reduced cisplatin uptake at the later time points. The organic cation
      tetraethylammonium (1 mm) reduced [(195m)Pt]cisplatin (31.7 mum) uptake to a
      greater extent than the organic anion p-aminohippuric acid (1 mm) suggesting
      preferential use of the cationic transport system by cisplatin. Biochemical
      perturbations observed included increased release of the lysosomal enzyme N
      acetyl-beta-d-glucosaminidase as well as a time- and concentration-dependent
      increase in lipid peroxidation. Cisplatin inhibited both nystatin-stimulated and
      ouabain-sensitive respiration (Qo(2)) after only 15 min of treatment. The
      biochemical changes observed were correlated with morphological alterations in
      the mitochondria. The results suggest that inhibition of oxidative
      phosphorylation may be a primary event in cisplatin-induced nephrotoxicity with
      later changes in lipid peroxidation and enzyme leakage.

PMID- 20693090
TI  - In vitro dermal absorption of pesticides: IV. In vivo and in vitro comparison
      with the organophosphorus insecticide diazinon in rat, guinea pig, pig, human and
      tissue-cultured skin.
AB  - In vitro skin absorption tests are currently being developed as an alternative to
      in vivo animal tests for predicting the degree of occupational exposure to
      pesticides. In the study reported here, in vitro percutaneous absorption tests
      were conducted with the (14)C-ring-labelled pesticide, diazinon, dissolved in
      acetone and applied to the dermatomed skin (0.5 mm) of a number of species at a
      dose rate of 9.5-16.7 mug/cm(2). Skin permeation was determined for 48 hr after
      exposure using an in vitro flow-through system. Skin permeation was calculated
      from the sum of the percentage recovery of (14)C activity in the receiver
      solution and the percentage recovery obtained in methanol washes of the skin at
      48 hr and in skin digests. Listed in decreasing order, the total percentage in
      vitro dermal absorptions (mean +/- SD) obtained by 48 hr after exposure for the
      five skin types were: 47 +/- 3.4% (rat), 36 +/- 0.9% (tissue cultured Testskin),
      33 +/- 2.8% (hairless guinea pig), 20 +/- 3.1% (human) and 15 +/- 13.1% (pig).
      The percentage recoveries in soapy water skin washes at 24 hr, in methanol washes
      and skin digests at 48 hr and of (14)C-labelled volatiles collected in air traps
      at 48 hr after exposure are reported. Comparative in vivo studies demonstrated 37
      +/- 0.8 and 24 +/- 5.7% recovery of (14)C in the urine of rats (dose rate, 6
      mug/cm(2)) and hairless guinea pigs (dose rate, 5 mug/cm(2)), respectively, by 14
      days after exposure. Total faecal recovery 14 days after exposure was 18 +/- 0.4
      and 4 +/- 0.9% for rats and guinea pigs, respectively. Analysis of tissue taken
      at autopsy 14 days after exposure demonstrated a total tissue recovery of 0.6 +/-
      0.1% [(14)C]diazinon in rats and 1 +/- 0.2% in hairless guinea pigs. The total
      recovery in skin removed from the dose site at 14 days after exposure was 0.2 +/-
      0.02% and 0.1 +/- 0.05% in rats and hairless guinea pigs, respectively. Recovery
      of radioactivity from soapy water skin washes conducted at 24 hr after exposure
      was 21 +/- 3.8% for rats and 2 +/- 0.1% for hairless guinea pigs. Recovery in
      skin patches was 23 +/- 5.4% and 73 +/- 2.9% in rats and hairless guinea pigs,
      respectively. The in vitro data for dermal absorption of [(14)C]diazinon for rats
      (47 +/- 3.4%) and hairless guinea pigs (33 +/- 2.8%) were in good agreement with
      the data observed for rats (56 +/- 1.03%) and hairless guinea pigs (28 +/- 6.0%)
      in vivo. This study supported the use of in vitro skin absorption tests as an
      alternative to in vivo animal testing.

PMID- 20693091
TI  - In vitro dermal absorption of pesticides: V. In vivo and in vitro comparison of
      the herbicide 2,4-dichlorophenoxyacetic acid in rat, guinea pig, pig, human and
      tissue-cultured skin.
AB  - In vitro dermal absorption tests were conducted with the (14)C-ring-labelled
      herbicide 2,4-dichlorophenoxyacetic acid (2,4-D), dissolved in acetone and
      applied to dermatomed skin (0.5 mm) of a number of species at dose rates of 7-8
      mug/cm(2). Skin absorption was determined for 48 hr after exposure using an in
      vitro flow-through system. Skin absorption was calculated from the sum of the
      percentage recovery of (14)C activity in the receiver solution and the percentage
      recovery in the methanol washes of the skin at 48 hr and the skin digest samples.
      Two receiver solutions, Ringer's saline, and Hanks' HEPES buffered saline with 4%
      serum albumin were used. Listed in decreasing order, the total percentage in
      vitro dermal absorptions obtained by 48 hr after exposure for the five skin types
      were: 47 +/- 4.3% [tissue cultured Testskin; Hanks' receiver (HR)], 40 +/- 4.5%
      (rat; HR), 19 +/- 1.8% (human; HR), 14 +/- 2.3% (hairless guinea pig; HR), 14 +/-
      8.8% (pig; Ringer's receiver). The percentage recovery of the radiolabel in soapy
      water skin washes at 24 hr, methanol washes and skin digests at 48 hr, and of
      (14)C-labelled volatiles collected in air traps at 48 hr after exposure are
      reported. Comparative in vivo studies were conducted for 14 days after exposure
      and demonstrated 32 +/- 3.9 and 28 +/- 7.8% recovery of (14)C in the urine of
      rats (dose rate, 3 mug/cm(2)) and guinea pigs (dose rate, 4 mug/cm(2)),
      respectively. Total faecal recovery was 2 +/- 0.3 and 9 +/- 3.5% for rats and
      guinea pigs, respectively. Analysis of tissue taken at autopsy 14 day after
      dosing demonstrated a total tissue recovery of (14)C activity of 1 +/- 0.1 and 2
      +/- 0.5% in rats and guinea pigs, respectively. Including the (14)C activity
      extracted from the skin removed from the dose site at 14 days after exposure, the
      total recovery of dermally absorbed residues was 49 +/- 10.4 and 40 +/- 9.9% in
      rats and guinea pigs, respectively. Recovery of (14)C activity from soapy water
      skin washes conducted at 24 hr after exposure was 28 +/- 8.1 and 43 +/- 9.0% for
      rats and guinea pigs, respectively. Recovery in skin patches was 18% (guinea
      pigs) and 26% (rats). In summary, the in vitro/in vivo concordance for the rat
      dermal absorption data was good but the in vitro data for hairless guinea pigs
      underestimated the in vivo absorption, and therefore for 2,4-D, rat skin may
      provide a better model of percutaneous absorption.

PMID- 20693092
TI  - In vitro dermal absorption of pesticides: VI. In vivo and in vitro comparison of
      the organochlorine insecticide DDT in rat, guinea pig, pig, human and tissue
      cultured skin.
AB  - In vitro dermal absorption tests were conducted with the (14)C-ring-labelled
      pesticide, 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (DDT) dissolved in
      acetone and applied to dermatomed skin (0.5 mm) of a number of species at dose
      rates of 16-27 mug/cm(2). Skin absorption was determined for 48 hr after exposure
      using in vitro flow-through cells. Skin absorption was calculated from the sum of
      the percentage recovery of (14)C activity in the receiver solution added to the
      percentage recovery for the methanol washes of the skin at 48 hr and the skin
      digest samples. Two receiver solutions, Ringer's saline (used with Moody
      aluminium cells), and Hanks' HEPES buffered saline with 4% serum albumin (used
      with Bronaugh flow-through cells) were used. Listed in decreasing order, the
      total percentage in vitro dermal absorptions obtained by 48 hr after exposure for
      the five skin types were: 42 +/- 2.6% [hairless guinea pig; Hanks' receiver
      (HR)], 34 +/- 10.5% (rat; HR), 28 +/- 13.2% [Testskin; Ringer's receiver (RR)],
      28 +/- 2.9% (human; HR), 22 +/- 3.3% (Testskin; HR), 18 +/- 6.2% (pig; RR) and 14
      +/- 2.1% (pig; HR). The percentage (14)C activity recovered in soapy water rinses
      of the skin specimens at 24 hr, and for methanol skin washes and skin digests at
      48 hr, and of (14)C-labelled volatiles collected in air traps are reported. Data
      obtained with pig and Testskin for DDT using the Moody flow-through permeation
      cell was compared with that obtained using the Bronaugh cell. Significantly
      greater (P < 0.05) percentage recovery was obtained for the soap washes at 24 hr
      of the skin following the Bronaugh procedure than was obtained with the Moody
      method. Comparative in vivo studies demonstrated urinary recovery was 2 +/- 0.5
      and 15 +/- 1.7% for rats (dose rate; 6 mug/cm(2)) and guinea pigs (dose rate: 9
      mug/cm(2)), respectively. Total faecal recovery was 20 +/- 1.9 and 44 +/- 2.75%
      for rats and guinea pigs, respectively. Analysis of tissue taken at autopsy 14
      days after dosing demonstrated total tissue recovery of 51 +/- 5.6% in rats but
      of only 3 +/- 0.7% in guinea pigs. Including the (14)C activity extracted from
      the skin removed from the dose site at 14 days after exposure, the total recovery
      of dermally absorbed residues was 73 +/- 5.9 and 62 +/- 4.1% for rats and guinea
      pigs, respectively. Recovery of (14)C from soapy water skin washes conducted at
      24 hr after exposure was 3 +/- 1.4 and 14 +/- 1.8% for rats and guinea pigs,
      respectively, and this was significantly less than that obtained by both the
      Bronaugh and Moody in vitro procedures. Skin patch recovery was 24% for both rats
      and guinea pigs. In summary, the in vitro data underestimed the degree of dermal
      absorption observed in vivo for both rats and guinea pigs, and this was thought
      to be due to an overly vigorous removal of the pesticide skin deposit by the soap
      washing procedures used in vitro in comparison with the in vivo washing
      procedure.

PMID- 20693093
TI  - Adult rat myocardial slices: A tool for studies of comparative cardiotoxicity.
AB  - The applicability of myocardial slices in comparative cardiotoxicity studies was
      investigated using the known cardiotoxicants allylamine (AAM) and doxorubicin
      (DOX). Precision-cut adult rat myocardial slices are a recently developed in
      vitro system. Previously, it has been demonstrated that myocardial slices are
      viable for up to 24 hr in organ culture. Myocardial slices exhibited a
      concentration- and time-dependent loss of viability in response to exposure to
      AAM or DOX (10(-7), 10(-6) or 10(-5)m) during 24 hr in culture, as assessed by
      biochemical parameters including protein synthesis, ATP content, lipid
      peroxidation and the loss of the cytosolic enzyme creatine kinase. Protein
      synthesis and ATP content were sensitive indicators of slice viability, while
      lipid peroxidation was affected only by 10(-5)m DOX. Myocardial slices appear to
      be a useful in vitro system for the study of the cardiotoxic potential of
      chemicals. The maintenance of normal cellular architecture makes myocardial
      slices uniquely attractive for these studies.

PMID- 20693094
TI  - Cadmium-induced lipid peroxidation in rat liver slices: A possible involvement of
      hydroxyl radicals.
AB  - Cadmium-induced lipid peroxidation (LPO) in the presence of various hydroxyl
      radical-generating media was studied in rat liver slices. In the absence of such
      media, Cd showed an inhibitory action on LPO in vitro. Cd-induced LPO in liver
      slices in the presence of OH radical-generating media was inhibited by
      antioxidants. The findings indicate that Cd induced LPO as a result of the
      presence of transition metal ions and the generation of hydroxyl radicals.

PMID- 20693095
TI  - Nephrotoxicity and uptake of 1-benzyl quinolinium in precision-cut rabbit renal
      cortical slices.
AB  - Nephrotoxicity studies have not always meshed toxicity with transport and uptake,
      although the two are interdependent. To begin to address this issue, a series of
      model organic cations (quaternary amines) was examined which revealed differences
      in toxicity that were not explained by slight structural variations. Thus, a
      single model organic cation, 1-benzyl quinolinium (BQ), was used to assess
      organic cations in rabbit renal cortical slices. Histopathological evaluation
      revealed that BQ produced site-specific injury in the S(3) region of the proximal
      tubule. Biochemical assays (K(+), qO(2) and ATP) revealed dose- and time
      dependent decreases of BQ-exposed slices over 2-12 hr. Cation transport (uptake
      of tetraethylammonium) was decreased by BQ at sub-toxic doses within 2 hr,
      although anion transport (uptake of p-aminohippurate) was not affected.
      Understanding the toxicity and transport of model cations such as BQ will help to
      identify the mechanisms associated with organic cation nephrotoxicity as well as
      to facilitate the use of transport parameters to prevent toxicity or prolong drug
      action of cations.

PMID- 20693096
TI  - Quantitative comparison of cytotoxicity of dental antiseptics to normal human
      oral keratinocytes in vitro.
AB  - The cytotoxicities of antiseptics used in dentistry were examined with normal
      human keratinocytes from the oral cavity by the uptake of neutral red (NR assay).
      The NR assay is a quantitative in vitro assay that distinguishes between viable,
      damaged or dead cells. Cultures from different individuals were established, and
      secondary cultures in serum-free medium were used. The amount of NR extracted
      from cells after a 3-hr uptake of the dye was linearly proportional to the number
      of cells exposed to the dye. The cytotoxicity of antiseptics used on mucous
      membranes in the oral cavity was determined from the dose-response curves of
      inhibition of NR uptake in cells treated with antiseptics for 2 days. As a
      quantitative measure of cytotoxicity, NR(50) (i.e. the concentration of
      antiseptics that resulted in a 50% decrease in NR uptake relative to untreated
      controls) was extrapolated from dose-response curves. The rank-order of
      cytotoxicities (NR(50)) was Hyamine (10% benzethonium chloride solution) >
      Hibitane (5% chlorhexidine gluconate solution) > acrinol (0.2% acrinol solution)
      > Iodine Carbol (liquefied phenol with 3% iodine) > iodine glycerin (glycerin
      with 10% iodine) > dilute iodine tincture (3% iodine solution) approximately
      iodine tincture (6% iodine solution) approximately Isodine (10% povidone-iodine
      solution) > Oxydol (3% hydrogen peroxide solution). These results provide useful
      estimates of relative toxicities of antiseptics to human cells, which can be
      compared with antimicro-organism activity to maximize therapeutic benefit with
      minimal toxicity.

PMID- 20693097
TI  - Counteraction by glutathione and selenium of the prooxidant effect of alloxan in
      erythrocytes in vitro.
AB  - Alloxan produces reactive oxygen species which cause injury to the insulin
      producing beta-cells of the pancreas. The action of alloxan in the production of
      free radicals was studied in vitro using rat erythrocytes. Alloxan increased
      lipid peroxidation (LPO) and decreased the activities of the antioxidant enzymes
      such as superoxide dismutase, catalase and glutathione peroxidase in the
      erythrocytes. Treatment with glutathione (GSH) and/or selenium along with alloxan
      was able to decrease LPO and increase the activities of the antioxidant enzymes
      in the erythrocytes. The results suggest that GSH and selenium both counteract
      the prooxidant effect of alloxan in rat erythrocytes.

PMID- 20693098
TI  - The classification of soluble silicates for eye hazard using the enucleated
      rabbit eye test.
AB  - Soluble silicates represent a broad range of chemical substances, which, to meet
      EEC laws, must be classified and labelled to identify their toxicological
      hazards. The wide range of this type of substance which can be manufactured, and
      the potentially severe effects which can be produced in standard eye irritation
      tests, means that classification by standard animal procedures is undesirable.
      One of the most reliable in vitro assays for assessing eye irritation potential
      is the rabbit enucleated eye test. This procedure has been used to test a range
      of soluble sodium silicates to enable these materials to be classified for eye
      hazard. The experimental approach demonstrates an important example of how an in
      vitro procedure can be used to propose classification for materials in a
      reasonable, scientifically valid way, taking account of the nature of the
      potential hazards and the intrinsic limitations of the in vitro methods used.

PMID- 20693099
TI  - Cytotoxic and mutagenic effects of anti- and syn-benzo[a]pyrene diol epoxide in
      human lymphocytes.
AB  - Cytotoxicity and mutagenicity were measured in human lymphocytes after treatment
      in vitro with anti- or syn-benzo[a]pyrene diolepoxide, two diastereoisomer
      metabolites of benzo[a]pyrene. These compounds were incubated with resting and
      cycling lymphocytes to determine the inhibition of cell proliferation induced by
      phytohemoagglutinin and interleukin2 at different times after treatment. Anti
      benzo[a]pyrene diolepoxide was more cytotoxic than the syn-adduct under all
      conditions, and its effect on cell growth was more marked in cycling lymphocytes.
      In contrast, neither of the compounds induced alteration of the ATP intracellular
      pool. Cytotoxic effects of anti- and syn-benzo[a]pyrene diolepoxide were also
      assessed by determining the cloning efficiency. Both compounds affected the
      cloning efficiency in human lymphocytes and the effect of anti-benzo[a]pyrene was
      particularly marked. Mutagenic potency of anti- and syn-benzo[a]pyrene
      diolepoxide at the hgprt locus was measured both in the V79 cell line and in
      human lymphocytes by selection of mutant cells in medium containing 6
      thioguanine. Both compounds increased the mutant frequency in comparison with the
      control and anti-benzo[a]pyrene diolepoxide was more active than the syn
      metabolite.

PMID- 20693100
TI  - The influence of vinyl-4-cyclohexene dioxide on the vimentin-containing
      intermediate filaments and the microtubular cytoskeleton of cultured mouse
      fibroblasts: Immunofluorescence investigations.
AB  - The exposure of 3T3 mouse fibroblasts to vinyl-4-cyclohexene dioxide (VCD), a
      compound used as a chemical intermediate and as a reactive diluent for diepoxides
      and epoxy resins, induces changes in cellular shape and cytoplasmic organization.
      Toxicological effects on the cytoskeletal elements were investigated by culturing
      3T3 cells in medium containing VCD for increasing times (15, 30, 60 and 180 min).
      The immunofluorescence investigations demonstrated that both vimentin-containing
      intermediate filaments and microtubules were compromised by the treatment in a
      time-dependent manner. Increasing the duration of exposure to VCD increased
      cellular damage.

PMID- 20693101
TI  - Cells of different tissues for in vitro and in vivo studies in toxicology:
      Compilation of isolation methods.
AB  - An advantage of using freshly isolated intact cells of different organs in
      toxicology is that they reflect more closely the in vivo situation than do long
      term cultures. In vitro, primary cells provide the possibility of determining
      cell-specific xenobiotic metabolism, in the absence of artificial extracellular
      activation systems, which may result in cytotoxic and genotoxic effects. After in
      vivo exposure of animals to xenobiotics, isolated primary cells can be studied to
      elucidate toxicokinetic effects. In the review presented here, selected methods
      are described for isolating cells with high viability from pig liver and avian
      embryonic liver, and from the nasal cavity, lungs, kidneys, gastro-intestinal
      tract, urinary bladder, testes and thymus of the rat. Two techniques for
      preparing rat lymphocytes are also described. Cell isolation may be initiated
      with an in situ perfusion to clear the organ of blood. Steps to loosen cell-to
      cell contacts and to digest the intercellular connective material may then
      follow. Also, in situ digestion may be performed, as described for the epithelial
      cells from different mucosal tissues. Following initial digestion, a single-cell
      suspension is prepared by tissue mincing and a second digestive step with
      proteolytic enzymes. Frequently used digestive enzymes are collagenase (types I,
      IV and P; from Clostridium histolyticum), trypsin and proteinase K. Follow-up
      filtration is usually required to remove undigested material. The quantities and
      viabilities of the harvested cells vary with the organ of choice and the
      procedure used; the values obtained are stated.

PMID- 20693102
TI  - In vitro cytotoxicity tests for the prediction of acute toxicity in vivo.
AB  - Investigations of the use of in vitro cytotoxicity tests for the prediction of
      acute toxicity in vivo have been reviewed with particular emphasis on those
      studies that have been published during the past 5 years. Numerous cell types,
      endpoints and exposure periods have been used in cytotoxicity tests, although
      these appear generally to have little effect on the resulting correlation between
      in vitro IC(50) values and in vivo LD(50) values. The in vitro data correlate
      better with rodent parenteral (ip or iv) LD(50) values than with oral LD(50)
      values due to kinetic considerations. For certain groups of related chemicals
      (e.g. antitumour compounds, metal salts), and for some sets of unrelated
      chemicals, the in vitro data correlate very well with LD(50) values. However,
      while cytotoxicity tests are useful for screening chemicals for their intrinsic
      and relative toxicities, it is impossible to tell whether predictions based on
      cytotoxicity data alone would be sufficiently accurate for labelling and
      classifying a new chemical according to its likely acute toxicity in vivo. The in
      vitro endpoints need to be of greater relevance to the possible mechanisms of
      chemically-induced acute toxicity in vivo than most of those that are used at
      present.

PMID- 20693103
TI  - Ethanol-induced downregulation of the angiotensin AT2 receptor in murine
      fibroblasts is mediated by PARP-1.
AB  - Molecular mechanisms accompanying ethanol-induced cytotoxicity remain to be
      defined. The renin-angiotensin system with its respective receptors, the
      angiotensin AT1 and AT2 receptor (AT1R and AT2R), has been implicated in these
      processes. The AT2R seems to counteract the pro-inflammatory, pro-hypertrophic,
      and pro-fibrotic actions of the AT1R and is involved in cellular differentiation
      and tissue repair. Recently, we identified poly(ADP-ribose) polymerase-1 (PARP-1)
      as a novel negative transcriptional regulator of the AT2R. However, the complex
      interactions between ethanol, PARP-1, and the AT2R are largely unknown. In this
      in vitro study, we aimed to clarify whether acute ethanol treatment modifies AT2R
      promoter activity or AT2R mRNA and protein levels and whether PARP-1 is involved
      in ethanol-mediated regulation of the AT2R. Murine fibroblasts of the R3T3 and
      MEF line (murine embryonic fibroblasts) were exposed to ethanol for 24h. AT2R
      promoter activity, mRNA and protein levels were analyzed with and without PARP-1
      inhibition and in PARP-1 knockout MEF cells. Expression of PARP-1 was analyzed
      over course of time, and cell viability and DNA fragmentation were measured on
      single-cell level by flow cytometry. Ethanol exposition induced substantial
      downregulation of the AT2R on promoter, mRNA and protein levels in a dose
      dependent manner. Pharmacological inhibition or ablation of PARP-1 completely
      abolished this effect. Ethanol treatment did not have any effect on AT1R mRNA and
      protein levels in MEF cells. Further, acute ethanol treatment promoted DNA
      fragmentation and caused transcriptional induction of PARP-1. Our findings reveal
      that PARP-1 is an upstream transcriptional regulator of the AT2 receptor in the
      context of ethanol exposure and represses the AT2R gene in fibroblasts in vitro.
      Variations in expression of the potentially tissue-protective AT2R might
      contribute to ethanol-mediated pathology.

PMID- 20693104
TI  - Multiscale recurrence quantification analysis of spatial cardiac vectorcardiogram
      signals.
AB  - Myocardial infarction (MI), also known as a heart attack, is a leading cause of
      mortality in the world. Spatial vectorcardiogram (VCG) signals are recorded on
      the body surface to monitor the underlying cardiac electrical activities in three
      orthogonal directions of the body, namely, frontal, transverse, and sagittal
      planes. The 3-D VCG vector loops provide a new way to study the cardiac dynamical
      behaviors, as opposed to the conventional time-delay reconstructed phase space
      from a single ECG trace. However, few, if any, previous approaches studied the
      relationships between cardiac disorders and recurrence patterns in VCG signals.
      This paper presents the recurrence quantification analysis (RQA) of VCG signals
      in multiple wavelet scales for the identification of cardiac disorders. The
      linear classification models using multiscale RQA features were shown to detect
      MI with an average sensitivity of 96.5% and an average specificity of 75% in the
      randomized classification experiments of PhysioNet Physikalisch-Technische
      Bundesanstalt database, which is comparable to the performance of human experts.
      This study is strongly indicative of potential automated MI classification
      algorithms for diagnostic and therapeutic purposes.

PMID- 20693105
TI  - Information filtering for ultrasound-based real-time registration.
AB  - This paper presents methods based on information filters for solving matching
      problems with emphasis on real time, or effectively real-time applications. Both
      applications discussed in this paper deal with ultrasound-based rigid
      registration in computer-assisted orthopedic surgery. In the first application,
      the usual workflow of rigid registration is reformulated such that registration
      algorithms would iterate while the surgeon is acquiring ultrasound images of the
      anatomy to be operated. Using this effectively real-time approach to
      registration, the surgeon would then receive feedback in order to better gauge
      the quality of the final registration outcome. The second application considered
      in this paper circumvents the need to attach physical markers to bones for
      anatomical referencing. Experiments using anatomical objects immersed in water
      are performed in order to evaluate and compare the different methods presented
      herein, using both 2-D as well as real-time 3-D ultrasound.

PMID- 20693106
TI  - A multistage approach to improve performance of computer-aided detection of
      pulmonary embolisms depicted on CT images: preliminary investigation.
AB  - This study developed a computer-aided detection (CAD) scheme for pulmonary
      embolism (PE) detection and investigated several approaches to improve CAD
      performance. In the study, 20 computed tomography examinations with various lung
      diseases were selected, which include 44 verified PE lesions. The proposed CAD
      scheme consists of five basic steps: 1) lung segmentation; 2) PE candidate
      extraction using an intensity mask and tobogganing region growing; 3) PE
      candidate feature extraction; 4) false-positive (FP) reduction using an
      artificial neural network (ANN); and 5) a multifeature-based k-nearest neighbor
      for positive/negative classification. In this study, we also investigated the
      following additional methods to improve CAD performance: 1) grouping 2-D detected
      features into a single 3-D object; 2) selecting features with a genetic algorithm
      (GA); and 3) limiting the number of allowed suspicious lesions to be cued in one
      examination. The results showed that 1) CAD scheme using tobogganing, an ANN, and
      grouping method achieved the maximum detection sensitivity of 79.2%; 2) the
      maximum scoring method achieved the superior performance over other scoring
      fusion methods; 3) GA was able to delete "redundant" features and further improve
      CAD performance; and 4) limiting the maximum number of cued lesions in an
      examination reduced FP rate by 5.3 times. Combining these approaches, CAD scheme
      achieved 63.2% detection sensitivity with 18.4 FP lesions per examination. The
      study suggested that performance of CAD schemes for PE detection depends on many
      factors that include 1) optimizing the 2-D region grouping and scoring methods;
      2) selecting the optimal feature set; and 3) limiting the number of allowed
      cueing lesions per examination.

PMID- 20693107
TI  - Case retrieval in medical databases by fusing heterogeneous information.
AB  - A novel content-based heterogeneous information retrieval framework, particularly
      well suited to browse medical databases and support new generation computer aided
      diagnosis (CADx) systems, is presented in this paper. It was designed to retrieve
      possibly incomplete documents, consisting of several images and semantic
      information, from a database; more complex data types such as videos can also be
      included in the framework. The proposed retrieval method relies on image
      processing, in order to characterize each individual image in a document by their
      digital content, and information fusion. Once the available images in a query
      document are characterized, a degree of match, between the query document and
      each reference document stored in the database, is defined for each attribute (an
      image feature or a metadata). A Bayesian network is used to recover missing
      information if need be. Finally, two novel information fusion methods are
      proposed to combine these degrees of match, in order to rank the reference
      documents by decreasing relevance for the query. In the first method, the degrees
      of match are fused by the Bayesian network itself. In the second method, they are
      fused by the Dezert-Smarandache theory: the second approach lets us model our
      confidence in each source of information (i.e., each attribute) and take it into
      account in the fusion process for a better retrieval performance. The proposed
      methods were applied to two heterogeneous medical databases, a diabetic
      retinopathy database and a mammography screening database, for computer aided
      diagnosis. Precisions at five of 0.809 +/- 0.158 and 0.821 +/- 0.177,
      respectively, were obtained for these two databases, which is very promising.

PMID- 20693108
TI  - Constructive approximation to multivariate function by decay RBF neural network.
AB  - It is well known that single hidden layer feedforward networks with radial basis
      function (RBF) kernels are universal approximators when all the parameters of the
      networks are obtained through all kinds of algorithms. However, as observed in
      most neural network implementations, tuning all the parameters of the network may
      cause learning complicated, poor generalization, overtraining and unstable.
      Unlike conventional neural network theories, this brief gives a constructive
      proof for the fact that a decay RBF neural network with n+1 hidden neurons can
      interpolate n+1 multivariate samples with zero error. Then we prove that the
      given decay RBFs can uniformly approximate any continuous multivariate functions
      with arbitrary precision without training. The faster convergence and better
      generalization performance than conventional RBF algorithm, BP algorithm, extreme
      learning machine and support vector machines are shown by means of two numerical
      experiments.

PMID- 20693109
TI  - Classification-based adaptive filtering for multiframe blind image restoration.
AB  - In this paper, the blind restoration of a scene is investigated, when multiple
      degraded (blurred and noisy) acquisitions are available. An adaptive filtering
      technique is proposed, where the distorted images are filtered, classified and
      then fused based upon the classification decisions. Finite normal-density mixture
      (FNM) models are used to model the filtered outputs at each iteration. For
      simplicity, fixed number of Gaussian components (classes) is, initially,
      considered for each degraded frame and the selection of the optimal number of
      classes is performed according to the global relative entropy criterion. However,
      there exist cases where dynamically varying FNM models should be considered,
      where the optimal number of classes is selected according to the Akaike
      information criterion. The iterative application of classification and fusion,
      followed by optimal adaptive filtering, converges to a global enhanced
      representation of the original scene in only a few iterations. The proposed
      restoration method does not require knowledge of the point-spread-function
      support size or exact alignment of the acquired frames. Simulation results on
      synthetic and real data, using both fixed and dynamically varying FNM models,
      demonstrate its efficiency under both noisy and noise-free conditions.

PMID- 20693110
TI  - Accelerating x-ray data collection using pyramid beam ray casting geometries.
AB  - Image reconstruction from its projections is a necessity in many applications
      such as medical (CT), security, inspection, and others. This paper extends the 2
      D Fan-beam method in [2] to 3-D. The algorithm, called Pyramid Beam (PB), is
      based upon the parallel reconstruction algorithm in [1]. It allows fast capturing
      of the scanned data, and in 3-D, the reconstructions are based upon the discrete
      X-ray transform [1]. The PB geometries are reordered to fit parallel projection
      geometry. The underlying idea is to use the algorithm in [1] by porting the
      proposed PB geometries to fit the algorithm in [1]. The complexity of the
      algorithm is comparable with the 3-D FFT. The results show excellent
      reconstruction qualities while being simple for practical use.

PMID- 20693111
TI  - Window-level rate control for smooth picture quality and smooth buffer occupancy.
AB  - In rate control, smooth picture quality and smooth buffer occupancy are both
      important but contrary to each other at a given bit rate. How to get a good
      tradeoff between them was not devoted much attention previously. To deal with
      this problem, a theoretical window model is proposed in this paper, in which
      several adjacent frames grouped as a window are considered together. The
      smoothness of both picture quality and buffer occupancy can be gracefully
      achieved by regulating the size of the window. To illustrate the usage of window
      model, a window-level rate control algorithm cooperated with the traditional rho
      domain rate-distortion model is further introduced. In experiments, we first show
      how the proposed window model achieves the tradeoff between picture quality
      smoothness and buffer smoothness, and then demonstrate the significant PSNR
      improvement, accuracy of bit control and consistency of visual quality of the
      proposed window-level rate control algorithm.

PMID- 20693112
TI  - From local pixel structure to global image super-resolution: a new face
      hallucination framework.
AB  - We have developed a new face hallucination framework termed from local pixel
      structure to global image super-resolution (LPS-GIS). Based on the assumption
      that two similar face images should have similar local pixel structures, the new
      framework first uses the input low-resolution (LR) face image to search a face
      database for similar example high-resolution (HR) faces in order to learn the
      local pixel structures for the target HR face. It then uses the input LR face and
      the learned pixel structures as priors to estimate the target HR face. We present
      a three-step implementation procedure for the framework. Step 1 searches the
      database for K example faces that are the most similar to the input, and then
      warps the K example images to the input using optical flow. Step 2 uses the
      warped HR version of the K example faces to learn the local pixel structures for
      the target HR face. An effective method for learning local pixel structures from
      an individual face, and an adaptive procedure for fusing the local pixel
      structures of different example faces to reduce the influence of warping errors,
      have been developed. Step 3 estimates the target HR face by solving a constrained
      optimization problem by means of an iterative procedure. Experimental results
      show that our new method can provide good performances for face hallucination,
      both in terms of reconstruction error and visual quality; and that it is
      competitive with existing state-of-the-art methods.

PMID- 20693113
TI  - Direct intermode selection for H.264 video coding using phase correlation.
AB  - The H.264 video coding standard exhibits higher performance compared to the other
      existing standards such as H.263, MPEG-X. This improved performance is achieved
      mainly due to the multiple-mode motion estimation and compensation. Recent
      research tried to reduce the computational time using the predictive motion
      estimation, early zero motion vector detection, fast motion estimation, and fast
      mode decision, etc. These approaches reduce the computational time substantially,
      at the expense of degrading image quality and/or increase bitrates to a certain
      extent. In this paper, we use phase correlation to capture the motion information
      between the current and reference blocks and then devise an algorithm for direct
      motion estimation mode prediction, without excessive motion estimation. A bigger
      amount of computational time is reduced by the direct mode decision and
      exploitation of available motion vector information from phase correlation. The
      experimental results show that the proposed scheme outperforms the existing
      relevant fast algorithms, in terms of both operating efficiency and video coding
      quality. To be more specific, 82 ~92% of encoding time is saved compared to the
      exhaustive mode selection (against 58 ~74% in the relevant state-of-the-art), and
      this is achieved without jeopardizing image quality (in fact, there is some
      improvement over the exhaustive mode selection at mid to high bit rates) and for
      a wide range of videos and bitrates (another advantages over the relevant state
      of-the-art).

PMID- 20693114
TI  - [Sexual risk factors and HIV seroprevalence among the deaf and hearing-impaired
      in Yaounde].
AB  - This quantitative cross-sectional study examines the sexual behaviour of people
      with hearing impairments in Yaounde, the capital of Cameroon, and measures the
      prevalence of HIV infection in this group. The study is intended to assess their
      sexual vulnerability and help to reduce the existing data gaps about HIV serology
      among people with disabilities in general and the deaf in particular. A snowball
      sampling procedure was adopted as an appropriate approach to this hard-to-reach
      population. In all, 118 deaf participants were interviewed in sign language for
      the behavioural component, and 101 participants provided blood samples for HIV
      serology testing. Descriptive analyses of behavioural data were performed with
      Epi info software, and health personnel used rapid and confirmation test reagents
      to diagnose HIV infection. The results make clear that the hearing-impaired are
      highly involved in risky sexual practices, as assessed by indicators including:
      age at first sexual intercourse, multiple sex partners, condom use, and knowledge
      of STIs and AIDS. Furthermore, HIV prevalence rate for the hearing-impaired in
      Yaounde was 4%, close to the level in the general population (4.7%). These
      results point to the need for in-depth behavioral research and serological
      studies in this domain, to improve our understanding of the determinants of risky
      sexual behaviours among the hearing-impaired and to help design operational
      prevention approaches for this target population.

PMID- 20693115
TI  - [Therapeutic alternatives to native L-asparaginase in the treatment of adult
      acute lymphoblastic leukemia].
AB  - L-asparaginase is an effective antineoplastic agent, which is an integral part of
      combination chemotherapy protocols for adult acute lymphoblastic leukemia. Its
      antitumor effect results from the depletion of asparagine, an amino acid
      essential to leukemia cells, and subsequent inhibition of protein synthesis
      leading to cytotoxicity. However, its use has been limited by a high rate of
      hypersensitivity reactions and development of neutrolizing anti-asparaginase
      antibodies, and by the need of frequent administration. To overcome these
      limitations modified versions of L-asparaginase (such as asparaginase from other
      sources, pegylated formulations, and asparaginase loaded into erythrocytes) have
      been recently proposed. Advantages of these therapeutic alternatives to native L
      asparaginase and their results as part of preliminary clinical trials in adults
      have been outlined in this review.

PMID- 20693116
TI  - [Prospective study of quality of life after cytoreductive surgery and
      hyperthermic intraperitoneal chemotherapy using oxaliplatin for peritoneal
      carcinomatosis].
AB  - BACKGROUND: Cytoreductive surgery followed by hyperthermic intraperitoneal
      chemotherapy (HIPEC) is now the reference technique for limited peritoneal
      carcinomatosis (PC). Operative mortality is actually at 3 or 4%, and decrease as
      morbidity. Together, they did not limit acceptation of HIPEC. However, one of the
      major limitation of this aggressive treatment is that patient can be afraid to
      impair overall quality of life (QoL). The aim of this article was to assess QoL
      in patients at least 12 months after HIPEC using Oxaliplatin. METHOD: Patients
      completed a questionnaire before and after surgery at 1, 3, 6 and 12 months. QoL
      was assessed with the EORTC QLQ-C30 questionnaire. RESULTATS: Between September
      2006 and October 2008, 32 of 35 patients who had undergone HIPEC were
      interviewed. PC originated in primary lesions of the colon/rectum (N = 17), ovary
      (N = 3), stomach (N = 3), appendix (N = 2), mesothelium (N = 2), pseudomyxoma
      peritonei (N = 3) and primary carcinoma of peritoneum (N = 2). The percentage of
      patients completing the questionnaire at each time point was: baseline = 87% (N =
      28); 1 and 3 months = 46% (N = 15); 6 months = 62% (N = 20); and 12 months = 59%
      (N = 19). Morbidity and mortality were respectively 35 and 5%. Median hospital
      stay was 19 days. QoL score had decreased considerably in 60% of patients in the
      early postoperative assessment period after HIPEC (1 month), as compared with
      baseline score. Forty five per cent had reported significant pain and limitations
      on physical functioning. QoL score had returned to baseline at 3 months in 53,3%
      of patients: 20% reported lack of energy and fatigue. Fifty-five and 73% of
      patients had recovered their overall QoL at 6 and 12 months, respectively. Also,
      psychosocial problems, diarrhea and constipation, and peripheral neuropathy of
      oxaliplatin were reported in 20% of survivors over the course of the first year
      after HIPEC. CONCLUSION: Short-term QoL with physical and functional well-being
      are impaired in the first few months after surgery plus HIPEC using oxaliplatin.
      Long-term QoL returns to baseline at 3 months; however 20% of patients still
      report psychosocial problems, gastrointestinal symptoms and oxaliplatin-induced
      neuropathy. It is useful and important for patients to see this HIPEC QoL data at
      the time of consultation before treatment.

PMID- 20693117
TI  - Giant left atrial myxoma with dual blood supply accompanying significant coronary
      artery stenosis.

PMID- 20693118
TI  - Aortico-left ventricular fistula associated with infective endocarditis.

PMID- 20693119
TI  - Huge main pulmonary arterial thrombus in a child with increased lipoprotein (a)
      level.

PMID- 20693120
TI  - Ventricular septal defect with bidirectional shunting in a patient with
      congenitally corrected transposition.

PMID- 20693121
TI  - Primary right atrial subendocardial lipoma.

PMID- 20693122
TI  - [Our first impact factor (IF) 0.378, new supplement, scientific summer school and
      targets].

PMID- 20693123
TI  - Effects of caffeic acid phenethyl ester on isoproterenol-induced myocardial
      infarction in rats.
AB  - OBJECTIVE: Caffeic acid phenethyl ester (CAPE) is a natural product with potent
      anti-inflammatory, antitumor and antioxidant activities and attenuates
      inflammation and lipid peroxidation induced by ischemia-reperfusion injury. The
      purpose of the present study was to investigate the effects of CAPE on
      isoproterenol (ISO) -induced myocardial infarction. METHODS: A randomized
      controlled experimental design was used in this study. Rats were divided into
      four groups and treated with saline, CAPE, ISO and ISO+CAPE. Rats were treated
      with CAPE (10 micromol kg/day i.p.) or saline starting 3 days before injecting
      ISO (150 mg /kg s.c., 24 hours). Seven days later, rats were sacrificed and the
      hearts were excised for biochemical analyses and microscopic examination. One-way
      ANOVA test with post hoc multiple comparisons using LSD method were used for
      statistical analysis of the data. RESULTS: The administration of ISO alone
      resulted in higher myeloperoxidase (MPO) activity, lipid peroxidation, superoxide
      dismutase (SOD) and catalase (CAT) than in the control. The enzyme activities did
      not change in rat given CAPE alone. CAPE treatment prevented the increase in MPO
      activity and malondialdehyde, but did not affect the activities SOD and CAT
      enzymes. CONCLUSION: In light of these results, we conclude that CAPE prevents
      MPO-and lipid peroxidation-mediated myocardial injury via inhibition of
      neutrophil's MPO activity.

PMID- 20693124
TI  - The variations of BOP gene in hypertrophic cardiomyopathy.
AB  - OBJECTIVE: The observation that Bop null allele mice show underdeveloped right
      ventricle and excessive development of left ventricle, suggests the possible
      relationship between human BOP gene and hypertrophic cardiomyopathy (HCMP). In
      our study, we investigated this possible relationship between BOP gene variations
      and QT dispersion, a noninvasive arrhythmic risk marker for HCMP. METHODS: This
      cross-sectional study consisted of 50 patients clinically diagnosed with HCMP and
      60 healthy subjects. Exonic regions of BOP gene were amplified by polymerase
      chain reaction and amplified exonic regions were analyzed by Single-Strand
      Conformation Polymorphisms (SSCP). The samples with different migration patterns
      were sequenced through an automated sequencing system. Continuous variables were
      compared by unpaired t-test for independent samples or Mann-Whitney U test.
      Genotype-disease relationship was tested by Chi-square test. RESULTS: The
      nucleotide substitutions G275<or=A and C965<or=A in exon 2 and 7 were determined
      only in HCMP group. The G707<or=C, C710<or=T, T761<or=C, T1217<or=C SNPs in exon
      6 and 9 are also found in the control group. Significant differences were found
      between two groups (p=0.002 and p=0.001). It was found that SNPs in exon 6
      constitute a haplotype and that QT dispersion and corrected QT dispersion in the
      rare homozygote (707C/710T/761C) type carriers of HCMP patients for this
      haplotype were significantly lower than other genotypes (p=0.032 and p=0.030,
      respectively). CONCLUSION: The human BOP gene was analyzed for the first time in
      HCMP to investigate possible association. The result that homozygosity of
      707C/710T/761C haplotype is associated with lower QT dispersion and corrected QT
      dispersion supports the modifier role of BOP gene in HCMP.

PMID- 20693125
TI  - Efficacy of levosimendan in patients with chronic heart failure: Does rhythm
      matter?
AB  - OBJECTIVE: Levosimendan is a relatively new inotropic agent. Unlike other
      inotropic agents, Levosimendan does not increase cellular calcium intake, so
      that, does not cause intracellular calcium overload and related arrhythmias.
      Atrial fibrillation (AF) was shown to be an independent risk factor for mortality
      and morbidity in large heart failure (HF) trials. Heart failure induces AF, AF
      aggravates HF and therefore they generally coexist. We conducted a study to
      investigate if there is any differential effect of Levosimendan in HF patients
      with chronic AF and without AF. METHODS: This is a prospective study. Consecutive
      patients, who were hospitalized because of acutely decompensated HF due to
      systolic dysfunction and decided Levosimendan administration, were enrolled.
      Patients were classified into two as those with AF (group A) and those with sinus
      rhythm (control group, group S). All patients had echocardiography before and
      after administration. Echocardiographic data were evaluated by ANOVA repeated
      measurements test. RESULTS: Baseline left ventricle ejection fraction (LVEF) was
      poorer in group with AF (mean LVEF for group A: 20.9%, for group S: 26.4%,
      p=0.04). Baseline diastolic parameters were equally impaired. After infusion,
      diastolic parameters like velocity of propagation (Vp) and isovolumic relaxation
      time (IVRT) improved almost to same extent in both groups but deceleration time
      (DT) did not. IVRT values decreased (p=0.012) both in group S (from 108.6+/-23.2
      msec to 100.4+/-28.4 msec) and group A (from 117.3+/-25.1 msec to 92.0+/-20.9
      msec) without a significant difference between groups (p=0.180 for interaction).
      Another valuable diastolic parameter, Vp was also similarly improved (p=0.01) in
      both groups to similar extent (for group A, from 35.4+/-8.8 cm/sec to 41.1+/-7.7
      cm/sec, for group S, from 33.7+/-7.5 cm/sec to 37.8+/-7.6 cm/sec; p=0.498 for
      interaction). CONCLUSION: We have shown that in patients with chronic HF and AF,
      levosimendan improves left ventricular systolic and diastolic functions as good
      as those with HF and sinus rhythm. We suggest that a positive
      electrophysiological effect of levosimendan on failing myocardial tissue seems to
      fill the absence of atrial booster in patients with AF who are on beta-blocker
      therapy.

PMID- 20693126
TI  - Plasma renin activity and pro-B-type natriuretic peptide levels in different
      atrial fibrillation types.
AB  - OBJECTIVE: Renin-angiotensin system may be activated during atrial fibrillation
      (AF). Our aim was to evaluate plasma renin activity (PRA) and N-terminal pro-B
      type natriuretic peptide (NT-proBNP) levels in patients with different AF types
      who had normal left ventricular (LV) systolic function. METHODS: This cross
      sectional study included 97 patients with recent (<or=7 days), persistent (7 days
      to 12 months) and permanent AF (<or=12 months), and age- and sex-matched 30
      controls with sinus rhythm. Plasma levels of PRA and NT-pro-BNP were measured and
      presented as median (25th-75th percentiles). Echocardiographic examination was
      performed in all population. Variance and logistic regression analyses were also
      used for multiple comparisons and independent predictors, respectively. RESULTS:
      Median NT-proBNP levels were higher in overall patients with AF than in controls
      [114 (63-165) vs 50 (38-58) pg/ml, p=0.001), but PRA level was comparable in both
      groups. Similarly, NT-proBNP levels were also higher in all subtypes of AF
      compared with controls (p=0.05). In addition, there was a significant difference
      in NT-proBNP level among recent, persistent and permanent AF subtypes (p=0.001).
      This difference mainly derived from the recent AF subtypes. Whereas PRA level was
      similar in all AF subtypes and controls. Age was an independent predictor of PRA
      level >or=1.9 ng/ml/hour (OR=1.1, 95% CI 1.01-1.23, p=0.03). With NT-proBNP level
      >or=52 pg/ml, independent predictors were age (OR=1.1, 95% CI 1.01-1.19, p=0.02),
      presence of persistent and/or permanent AF (OR=6.8, 95% CI 1.03-45.7, p=0.04) and
      left atrial dimension (OR=1.2, 95% CI 1.03-1.36, p=0.02). CONCLUSION: Plasma NT
      proBNP levels can be associated with AF and its subtypes in patients with normal
      LV systolic function, whereas there was no association between PRA levels and AF.

PMID- 20693127
TI  - [The effect of atrial pacing on left ventricular diastolic function and BNP
      levels in patients with DDD pacemaker].
AB  - OBJECTIVE: We aimed to investigate the effect of atrial pacing on left
      ventricular diastolic function and brain natriuretic peptide (BNP) levels in
      patients with DDD pacemaker. METHODS: Thirty patients with complete atrio
      ventricular (AV) block and DDD pacemaker were included. All patients had normal
      left ventricular systolic function. Echocardiographic diastolic function
      parameters (transmitral and tissue Doppler velocities during early (E and E') and
      late (A and A') filling) and NT-pro-BNP levels were evaluated prospectively
      during atrial sensing and pacing periods. Echocardiographic data were compared
      with paired sample t test and NT-pro-BNP levels were compared with Wilcoxon test.
      RESULTS: Echocardiographic E/A, E'/A', E/E' ratios were calculated as 0.72+/
      0.34, 0.61+/-0.21 and 8.76+/-2.58 during atrial sensing period. Same parameters
      were found as 0.71+/-0.23, 0.64+/-0.16 and 8.93+/-3.16 respectively during atrial
      pacing period. Echocardiographic left ventricular diastolic function parameters
      were not significantly different during atrial pacing and atrial sensing periods.
      Median plasma NT-pro-BNP levels were measured as 142 pg/ml (min-max 47-563 pg/ml)
      and 147 pg/ml (min-max 33-1035 pg/ml) during atrial sensing and pacing periods
      respectively. These levels were not significantly different (p=0.86). CONCLUSION:
      The result of this study has shown that, atrial pacing has not any additional
      detrimental effect on left ventricular diastolic function parameters in paced
      patients with normal left ventricular systolic function.

PMID- 20693128
TI  - Evaluation of left ventricular function with strain/strain rate imaging in
      patients with rheumatic mitral stenosis.
AB  - OBJECTIVE: The most important sequel of acute rheumatic fever is mitral stenosis
      in long-term. The aim of the study is to determine left ventricular (LV)
      functions by tissue Doppler imaging (TDI) and strain/strain rate echocardiography
      (SE/SRE) in mitral stenosis patients who had no clinical signs of heart failure.
      METHODS: Our study was designed as cross-sectional study. The study population
      consisted of 32 patients with isolated mitral stenosis and mitral valve area =
      2.0 cm(2) (Group 1) and 25 healthy control subjects (Group 2). In addition to
      standard echocardiographic methods, TDI and SE/SRE were performed to assess LV
      functions in all participants. Student's t-test was used to compare continuous
      variables. Fisher- exact test was used to compare categorical variables. RESULTS:
      Systolic myocardial velocity (Sm) were significantly lower in Group 1 than in
      Group 2 (6.0+/-1.4 cm/sec vs 7.9+/-1.8 cm/sec, p=0.001) also, early diastolic
      myocardial velocity (Em) were significantly lower in Group 1 than in Group 2
      (4.4+/-1.5 cm/sec vs 10.8+/-2.1 cm/sec, p=0.001). But there was no significant
      difference in late diastolic myocardial velocity (Am) between two groups. Peak
      systolic strain and strain rate of septal wall in Group 1 were significantly
      lower than Group 2 (p=0.001 for both). Besides, peak systolic strain and strain
      rate of lateral wall in Group 1 were significantly lower than in Group 2 (p=0.001
      for both). CONCLUSION: Although, global ejection fraction was normal and there
      were no symptoms of heart failure clinically in the patients with mitral
      stenosis, LV dysfunction demonstrated that using by echocardiography. TDI and
      strain/strain rate imaging to be new echocardiographic methods may be used
      reliably for detection LV function in early stage of mitral stenosis.

PMID- 20693129
TI  - Myocardial perfusion SPECT and dobutamine stress tissue Doppler imaging in
      evaluation of patients with stable angina pectoris.
AB  - OBJECTIVE: To evaluate longitudinal function of ischemic and nonischemic
      myocardial tissue detected by Tc-99m MIBI single photon emission computed
      tomography (SPECT) prior to coronary revascularization in patients with stable
      angina pectoris. METHODS: We studied 24 consecutive patients (mean age 62+/-9
      years; 5 women) with stable angina pectoris. All patients underwent myocardial
      perfusion SPECT. Tissue Doppler imaging (TDI) was performed to detect myocardial
      systolic velocities of anterior, inferior, septum and lateral walls at rest and
      peak dobutamine stress. RESULTS: A total of 96 segments were visualized with
      SPECT study. Maximum mean septal, lateral, anterior and inferior TDI systolic
      velocities were similar in ischemic and nonischemic segments (6.73+/-1.04 cm/sec,
      6.93+/-1.34 cm/sec, respectively) at rest. At peak stress, maximum mean TDI
      systolic velocities were lower in the 37 ischemic segments (11.00+/-2.03 cm/sec)
      than 59 nonischemic segments (13.76+/-1.97 cm/sec, p = 0.001). Because we
      detected ischemia in whole group using both diagnostic tests, coronary
      angiography was decided. Critical coronary artery stenosis related to ischemic
      segments was detected and coronary revascularization decided. CONCLUSION: TDI
      with dobutamine stress can be used in patients with stable angina pectoris. In
      this study, we observed that quantitative data by TDI associated with SPECT
      showed an agreement for coronary revascularization.

PMID- 20693130
TI  - Comparison of intracoronary versus intravenous administration of tirofiban in
      primary percutaneous coronary intervention.
AB  - OBJECTIVE: The purpose of this study was to compare the intravenous bolus dose of
      tirofiban with intracoronary bolus dose in primary percutaneous coronary
      intervention (PCI) with regard to in hospital and six months clinical outcomes
      and peak cardiac enzyme levels. METHODS: We retrospectively examined 84 ST
      elevation myocardial infarction (STEMI) patients who underwent primary PCI from
      March 2006 to February 2007. All patients received the systemic bolus dose of
      tirofiban 10 mcg/kg either via intracoronary (IC) or intravenous (IV) route,
      followed by a 36 hours of IV infusion at 0.15 mcg/kg/min. Thirty six patients in
      IC group were compared with 48 patients in IV group in terms of peak cardiac
      enzyme levels, in-hospital and six months major adverse cardiac events (MACE)
      rates (death, myocardial infarction and repeat revascularization). Fisher's exact
      test, Yates Chi-square, unpaired Student's t-test and Mann-Whitney U test were
      used for statistical analysis. RESULTS: There was no difference in cardiovascular
      risk profile or cardiac history between two groups. At six months the incidence
      of MACE was 6.25% in IV group and 11.1% in IC group (p=0.45). Peak cardiac
      phosphokinase (CPK) levels between IV and IC groups were also statistically non
      significant (2657+/-2181 U/L in IV group and 2529+/-1929 U/L in IC group)
      (p=0.92). CONCLUSION: Intracoronary bolus application of tirofiban was not
      associated with reduction in MACE rates compared to intravenous administration in
      patients with STEMI who underwent primary PCI. Future prospective trials with
      higher bolus doses of IC tirofiban should addressed to clarify this issue.

PMID- 20693131
TI  - Investigation of relationship between the D-dimer and ischemia-modified albumin
      levels with the radiological imaging-based pulmonary embolism severity score in
      acute pulmonary embolism.
AB  - OBJECTIVE: To investigate possible relationship between the D-dimer and ischemia
      modified albumin (IMA) levels and radiological imaging-based severity scores in
      pulmonary embolism (PE) based on two different radiological characteristics; the
      pulmonary arterial obstruction index (PAOI) and the right ventricle/left
      ventricle (RV/LV) ratio. METHODS: In this prospective cohort study, forty-seven
      patients presenting to the emergency department and definitively diagnosed with
      PE using spiral computerized tomography (CT) were initially enrolled in the
      study. Levels of IMA and D-dimer were assessed colorimetrical and immuno
      turbidimetric methods, respectively. The PAOI and RV/LV ratios were calculated
      from CT images. The levels of biochemical parameters between the groups were
      compared with use of Mann-Whitney U and Kruskal-Wallis tests and relationship
      between the radiological scores were assessed using the Spearman correlation
      test. RESULTS: Analysis of the calculated PAOI and RV/LV ratio revealed a
      significant correlation between them (r=0.36, p=0.023). D-dimer levels differed
      considerably among the mild (=40%), moderate (40%-60%) and severe (60%) groups
      constituted on the basis of PAOI (p=0.039). This difference stemmed from those in
      D-dimer levels in the mild group, PAOI =40 % and the severe group, PAOI 60%
      (p=0.02; Z= -2.328). In addition, D-dimer levels and PAOI revealed a positive
      correlation, but no similar correlation was determined between D-dimer levels and
      RV/LV. There were no significant correlations between IMA and D-dimer levels,
      PAOI and RV/LV ratios. CONCLUSION: In the biochemical determination of severity
      of PE based on radiological characteristics, D-dimer may be a more relevant
      marker than IMA, which has been proposed as a new marker.

PMID- 20693132
TI  - Angiocardiography and magnetic resonance imaging to assess pulmonary
      regurgitation in repaired tetralogy of Fallot.
AB  - OBJECTIVE: This study aimed to compare the results of angiocardiography and
      cardiovascular magnetic resonance imaging in the assessment of pulmonary
      regurgitation following repair of tetralogy of Fallot. METHODS: We prospectively
      studied 37 patients with repaired tetralogy of Fallot. After routine examination
      cardiovascular magnetic resonance imaging (CMR) and cardiac catheterization and
      angiography were performed. Pulmonary regurgitation (PR) was classified according
      to the following criteria, using a left lateral angiogram of the main pulmonary
      artery; insufficiency jet is limited to right ventricular outflow tract (mild);
      jet reaches the body of right ventricle (moderate); jet fills the apex of the
      right ventricle (severe). RESULTS: Pulmonary regurgitation determined by
      angiocardiography and CMR was severe in 51.4% and 32.4%, moderate in 27% and
      40.5%, and none or mild in 21.6% and 27% of patients respectively. The ability of
      semi-quantitative estimation of PR determined by cardiac catheterization to
      distinguish between mild, moderate and severe pulmonary regurgitation was shown
      to have significant correlation with pulmonary regurgitant fraction obtained by
      CMR. CONCLUSIONS: Angiography obtained during invasive study can be used for the
      diagnosis and follow-up of pulmonary regurgitation confidently in patients with
      repaired tetralogy of Fallot and residual pulmonary regurgitation.

PMID- 20693133
TI  - [Clinical outcome and factors affecting surgical decision for repair versus
      replacement in patients with mitral regurgitation].
AB  - OBJECTIVE: We aimed to identify characteristics differentiating patients
      undergoing mitral valve replacement versus valve repair for mitral regurgitation
      (MR) and to investigate retrospectively mid-term clinical and functional
      outcomes. METHODS: From January, 2004 to January, 2009 146 patients underwent
      mitral valve surgery (62 male / 84 female; age: 55.9+/-13.6 [18-80] years) by one
      surgical team. Mitral valve replacement was performed in 101 patients (69.2 %)
      and valve repair was performed in 45 patients (30.8%). Mean follow-up time was
      586+/-413 days. Life tables were constructed for the analysis of 5-year
      complication free survival and comparisons were performed between the groups
      using Log-rank test within 95%CI. RESULTS: The choice of surgical technique
      depended on the etiology of MR. Degenerative (p=0.001) and ischemic (p=0.014) MR
      were more common in patients undergoing repair whereas patients with complex
      rheumatic mitral valve disease (p=0.001) with subvalvular involvement commonly
      underwent replacement. Overall 30-day mortality was 3.2% (replacement, 3.96%vs
      repair, 2.22%, p=0.59). Although there was no significant difference between the
      groups regarding baseline left ventricular ejection fraction (EF) (ischemic
      p=0.61; non-ischemic p=0.34), improvement was more pronounced in the repair group
      for both etiologies (ischemic MR, p=0.001; non- ischemic MR p=0.002). Survival at
      5-years was 91.7+/-4.7% after repair and 83.5+/-9.2% after replacement,
      respectively (p=0.83). Freedom from grade 2 or more mitral regurgitation,
      reoperation, endocarditis, and thromboembolism were 95+/-5% vs 97+/-3% (p=0.71);
      95+/-4% vs 98+/-2% (p=0.98); 94+/-4% vs 100% (p=0.16); and 85+/-8% vs 100%
      (p=0.095) in replacement and repair groups, respectively. CONCLUSION: This study
      demonstrates that mitral valve repair is associated with an acceptable operative
      mortality, satisfactory mid-term survival and better preservation of left
      ventricular function. Significant differences in favor of repair are expected in
      long-term follow-up particularly regarding freedom from thromboembolism and
      endocarditis.

PMID- 20693134
TI  - Rationing healthcare: Should life-style be used as a criterion?
AB  - Health is considered as important due to its impacts on individuals' lives.
      Although individual health level is determined partly by the accessibility of the
      services and their quality, there are many other factors that may influence an
      individual's health condition, which are mainly social determinants. Since there
      are many factors that determine health conditions of the individuals, it would be
      wrong to hold someone totally responsible for her health condition on the basis
      of her life-style; such as prudency. Indeed, before deciding about whether the
      patient was prudent or not; first, we have to look at those determinants of
      health, and investigate whether there is an effective intervention to avoid those
      determinants. Furthermore, life-styles of the individuals, which are thought to
      be the personal choices, are just one of the relatively less effective factors
      that may influence a person's health and also the autonomy of those choices is
      controversial. In our paper, we will endeavor to develop an argument showing that
      since health is one of our primary goods that needs to be protected as one of our
      basic human rights, and since the health status of individuals are not determined
      only by their personal choices, we claim that it would be unfair to consider
      accessing healthcare as something removable or limitable based on conditions
      other than medical criteria.

PMID- 20693135
TI  - Effects of glucose-insulin-potassium solution on acute myocardial infarction
      outcome in patients received streptokinase according to Killip classes.

PMID- 20693136
TI  - An isolated right ventricular myocardial infarction and severe tricuspid
      regurgitation due to occlusion of a non-dominant right coronary artery: role of
      delayed revascularization.

PMID- 20693137
TI  - Lightning-induced lethal myocardial infarction and ventricular tachycardia in a
      boy.

PMID- 20693138
TI  - Necessity of adequate monitoring during carotid body tumors.

PMID- 20693139
TI  - Kounis syndrome: A forgotten cause of chest pain/ Cardiac chest pain in children.

PMID- 20693140
TI  - Swyer-James syndrome or destroyed lung?/Coronary artery bypass in a patient with
      Swyer-James syndrome due to pulmonary tuberculosis.

PMID- 20693141
TI  - [Cigarette smoking and metabolic syndrome in Turkish women/Frequency and
      affecting factors of metabolic syndrome in women older than 20 years of
      age/Metabolic syndrome: importance and prevention].

PMID- 20693142
TI  - Problem-oriented education and cross-cultural collaboration: experiences and
      comments on the Scientific Summer School in Turkey 2010.

PMID- 20693143
TI  - [Hormonal imprinting--the unforeseeable future].
AB  - Hormonal imprinting takes place at the first encounter between the developing
      receptor and the target hormone, perinatally, causing life-long changes in the
      binding capacity of the receptor and the indexes influenced by it. Perinatal
      hormonal imprinting is absolutely needed for the maturation of receptor, however,
      at the same time, molecules similar to the target hormone (related hormones,
      synthetic drugs acting at receptor level, chemicals, environmental pollutants
      etc.) can cause faulty imprinting, also with (morphological, biochemical,
      receptorial, behavioral) consequences for life. Although imprinting is
      characteristic and inevitable perinatally, it can be provoked in any period of
      life in developing cells, especially at the weanling and adolescent age (late
      imprinting). There is no gene mutation during imprinting, however, the
      methylation pattern of the genes changes and that inherits epigenetically the
      imprinting, which is manifested in disposition to diseases or in diseases (e.g.
      tumor formation, metabolic syndrome). Imprinting is inherited between generations
      that could cause--in the present chemical world--evolutionary consequences. Thus,
      medicaments or preventive drugs, e.g. pregnancy protecting drugs or oral
      contraceptive pills should be given cautiously, especially in the critical
      periods, considering that consequences are manifested always after a long period
      (sometimes decades) or in the next generations.

PMID- 20693144
TI  - [Quality colonoscopy: assumptions and expectations].
AB  - Colonoscopy has become accepted as the most effective method of screening of the
      colon for neoplasia. Evidences prove that utilization of colonoscopy has
      increased dramatically in the past few years, largely because of increased rates
      of CRC screening. Effectiveness and safety of colonoscopy depend on the quality
      of examination, and growing body of evidence suggests that the quality of
      colonoscopy varies in clinical practice. Quality assurance of colonoscopy could
      be expected to contribute significantly to improved patient care. There is a
      clear need for evidence-based quality measures to ensure the quality of
      colonoscopy. In this review we present an overview of literature concerning
      criteria for best practice and important quality indicators for colonoscopy.

PMID- 20693145
TI  - [Sepsis-associated encephalopathy].
AB  - Sepsis-associated encephalopathy is a common but neglected clinical symptom of
      systemic inflammatory reaction in the early phase. The clinical spectrum of
      diffuse cerebral dysfunction induced by systemic sepsis--sepsis-associated
      encephalopathy according to the new terms--varies from transient, reversible
      encephalopathy, to severe irreversible brain damage. The aim of the present
      publication is to summarize the pathophysiology, frequent symptoms and possible
      treatments of the disease based on international and Hungarian articles on this
      topic. We want to emphasize the importance of monitoring the patient's mental
      status due to the fact that consciousness' disturbance of different severity is
      an early warning sign of sepsis, so it has high clinical significance.

PMID- 20693146
TI  - [Anemia in pregnancy: characteristics in Szabolcs-Szatmar-Bereg County, Hungary].
AB  - Nowadays anemia is the most common disease of internal medicine during pregnancy.
      It could cause harmful consequences both to mother and to child. AIM: authors
      examined connection between the blood count data (hemoglobin, red cell mean
      corpuscular volume), the ferritin level and the pregnancy age, the mothers' age,
      schooling, the number of earlier pregnancies, abortions and miscarriages
      frequency of women who gave birth in 2008 at Szabolcs-Szatmar-Bereg County,
      Hungary. METHODS: Authors analyzed the records of health visitors in 2008 year in
      their county. RESULTS: rate of anemia's occurrence in the first trimester was
      2.54%, 0.71% in the second and 1.87% in the third trimester, and it was
      significantly frequented among the youthful (10.30%), the low schooled (5.55%),
      and the multipara women (2.56%). There was no difference in the rate of
      abortions; however, miscarriages were more frequent among pregnant women with
      anemia (7.14% vs. 5.46%). Low mean red cell corpuscular volume values were more
      frequent in all groups (6.06-22.88%) then the number of pregnant women with
      anemia. This fact refers to decreased iron stores in most cases. Ferritin level
      determination was made in 2.42% of cases only, but among these pathological low
      values was found in 93.1%. CONCLUSIONS: Authors draw attention to the careful
      nursing of youthful, low schooled and multipara pregnant women, majority of them
      suffer from iron deficiency. They call attention to the right analysis of blood
      count, the start of correct iron supplementation in early pregnancy and the need
      of correction of iron stores before conception, too. Authors also give
      recommendations to this work on the basis of references.

PMID- 20693148
TI  - Supporting informed decision making for prostate specific antigen (PSA) testing
      on the web: an online randomized controlled trial.
AB  - BACKGROUND: Men considering the prostate specific antigen (PSA) test for prostate
      cancer, an increasingly common male cancer, are encouraged to make informed
      decisions, as the test is limited in its accuracy and the natural history of the
      condition is poorly understood. The Web-based PSA decision aid, Prosdex, was
      developed as part of the UK Prostate Cancer Risk Management Programme in order to
      help men make such informed decisions. OBJECTIVES: The aim of this study was to
      evaluate the effect of the Web-based PSA decision aid, Prosdex, on informed
      decision making. METHODS: A Web-based randomized controlled trial was conducted
      in South Wales, United Kingdom. Men aged 50 to 75 who had not previously had a
      PSA test were randomly allocated to two intervention and two control groups.
      Participants in the intervention groups either viewed Prosdex or were given a
      paper version of the text. The main outcome measures were the three components of
      informed decision making: (1) knowledge of prostate cancer and PSA, (2) attitude
      toward PSA testing, (3) behavior using a proxy measure, intention to undergo PSA
      testing. Decisional conflict and anxiety were also measured as was uptake of the
      PSA test. Outcomes were measured by means of an online questionnaire for the
      Prosdex group, the paper version group, and one of two control groups. Six months
      later, PSA test uptake was ascertained from general practitioners' records, and
      the online questionnaire was repeated. Results are reported in terms of the Mann
      Whitney U-statistic divided by the product of the two sample sizes (U/mm), line
      of no effect 0.50. RESULTS: Participants were 514 men. Compared with the control
      group that completed the initial online questionnaire, men in the Prosdex group
      had increased knowledge about the PSA test and prostate cancer (U/mn 0.70; 95% CI
      0.62 - 0.76); less favourable attitudes to PSA testing (U/mn 0.39, 95% CI 0.31 -
      0.47); were less likely to undergo PSA testing (U/mn 0.40, 95% CI 0.32 - 0.48);
      and had less decisional conflict (U/mn 0.32, 95% CI 0.25 - 0.40); while anxiety
      level did not differ (U/mn 0.50, 95% CI 0.42 - 0.58). For these outcomes there
      were no significant differences between men in the Prosdex group and the paper
      version group. However, in the Prosdex group, increased knowledge was associated
      with a less favourable attitude toward testing (Spearman rank correlation [rho] =
      -0.49, P < .001) and lower intention to undergo testing (rho = -0.27, P = .02).
      After six months, PSA test uptake was lower in the Prosdex group than in the
      paper version and the questionnaire control group (P = .014). Test uptake was
      also lower in the control group that did not complete a questionnaire than in the
      control group that did, suggesting a possible Hawthorne effect of the
      questionnaire in favour of PSA testing. CONCLUSIONS: Exposure to Prosdex was
      associated with improved knowledge about the PSA test and prostate cancer. Men
      who had a high level of knowledge had a less favourable attitude toward and were
      less likely to undergo PSA testing. Prosdex appears to promote informed decision
      making regarding the PSA test. TRIAL REGISTRATION: ISRCTN48473735;
      http://www.controlled-trials.com/ISRCTN48473735 (Archived by WebCite at
      http://www.webcitation.org/5r1TLQ5nK).

PMID- 20693149
TI  - Low seroprevalence of syphilis in Burkina Faso.
AB  - BACKGROUND: Little information is available on the epidemiology of syphilis in
      West Africa, where this infection is routinely screened in antenatal clinics to
      prevent congenital infection. In order to inform control programmes, the burden
      of active syphilis was estimated among pregnant women and adults in Burkina Faso.
      METHODS: This study enrolled 2136 pregnant women from 98 healthcare facilities
      and 1679 consenting women and men from the general population of Ouagadougou, the
      capital city. After a face-to-face interview on demographic characteristics,
      blood samples were collected and tested for syphilis. Active syphilis was defined
      by a dually positive result on rapid plasma reagin and Treponema pallidum
      haemagglutination antibody tests. RESULTS: The overall seroprevalence of active
      syphilis was 1.7% (95% CI 1.3 to 2.2), with similar rates between women (1.2%,
      95% CI 0.7 to 2.3) and men (1.8%, 95% CI 1.0 to 3.0) in Ouagadougou, and a trend
      for higher prevalence among pregnant women from semi-urban areas (2.2%, 95% CI
      1.0 to 4.5) compared with rural areas (1.7%, 95% CI 1.2 to 2.4, p = 0.06). The
      prevalence tended to be higher among women aged 20-24 years (2.6%, 95% CI 1.3 to
      7.6) and men aged 30-34 years (3.9%, 95% CI 0.8 to 11.0) than at other ages.
      However, age, marital status, location and education were not associated with
      syphilis. CONCLUSION: The low prevalence of syphilis among pregnant women and the
      adult general population is very encouraging but should not challenge the amount
      of resources dedicated to sexually transmitted infection and HIV prevention.

PMID- 20693150
TI  - Evolving role of cardiac CT in the diagnosis of coronary artery disease.
AB  - Non-invasive assessment of coronary artery patency has been attempted with
      different imaging modalities over the last few decades. The continuous motion of
      the heart, the respiratory movement, together with the small and tortuous nature
      of the coronary arteries, made this a technically challenging task. Over the last
      decade, significant advances in computed tomography (CT) technology helped CT
      coronary angiography (CTCA) to evolve as a non-invasive alternative to
      conventional catheter based coronary angiography. Clinical experience with CTCA
      has since grown rapidly and led to its acceptance as a useful diagnostic
      technique for coronary artery disease in certain patient populations. Recently,
      there has been exponential growth in the availability and use of CTCA in several
      centres across the world. In order to appreciate the potential impact of CTCA on
      current clinical practice, it is important to understand its advantages and
      limitations and its clinical performance in comparison with established
      techniques.

PMID- 20693151
TI  - Concurrent comparison of epidemiology, clinical presentation and outcome between
      adult patients suffering from the pandemic influenza A (H1N1) 2009 virus and the
      seasonal influenza A virus infection.
AB  - PURPOSE OF STUDY: The demographics, clinical features and outcome of patients
      with pandemic influenza A (H1N1) 2009 infection were compared with a concurrent
      cohort of patients with seasonal influenza A infection. STUDY DESIGN: The
      clinical and microbiological data of hospitalised adult patients admitted between
      29 June and 28 October 2009, with pandemic A (H1N1) 2009 or seasonal influenza A
      infection, were analysed. RESULTS: A total of 186 patients including 69 pandemic
      A (H1N1) and 117 seasonal influenza were analysed. The majority (75%) under 50
      years of age had pandemic A (H1N1). Compared with seasonal influenza, pandemic A
      (H1N1) patients were younger (median age 47 years vs 76 years, p<0.001), less
      likely to have lower respiratory tract symptoms (46.4% vs 66.7%, p=0.007), but
      more likely to be obese (5.8% vs 0%, p=0.018), pregnant (7.2% vs 0.9%, p=0.027)
      or have no underlying predisposing factors (24.6% vs 5.1%, p<0.001). Patients
      with pandemic A (H1N1) were more likely to receive oseltamivir (91.3% vs 40.2%,
      p<0.001), but less likely to receive antibiotics (75.4% vs 90.6%, p=0.005).
      Respiratory failure was the reason for intensive care unit admission for all four
      patients with pandemic A (H1N1), but only for one of three patients with seasonal
      influenza. There were no statistical significant differences in the rate of
      intensive care unit admission or death. CONCLUSIONS: In addition to age, several
      clinical parameters were different between pandemic A (H1N1) and seasonal
      influenza. However, since both seasonal and pandemic influenza can lead to
      significant morbidity and mortality, the impact of pre-existing seasonal
      influenza should not be underestimated during the pandemic period.

PMID- 20693152
TI  - Making time for partnership.

PMID- 20693153
TI  - Barotrauma related extensive pneumothorax, pneumomediastinum, and subcutaneous
      emphysema in a patient with acute respiratory distress syndrome with low tidal
      volume.

PMID- 20693154
TI  - A serious complication of selected internal radiation therapy: case report and
      literature review.
AB  - The use of selective internal radiation therapy (SIRT) with SIR-Spheres(R)
      (Sirtex, Sydney, Australia) is increasingly recognized as a potential therapeutic
      modality of primary and secondary malignant liver tumors. A number of treatment
      related complications have been described despite technical expertise and
      detailed pretreatment investigations to assess suitability. We describe a case of
      gastric ulceration from nontargeted deposition of SIR-spheres(R) in the gastric
      mucosa with life-threatening consequences. This case highlights the need for
      careful screening and appropriate patient selection, and the need to recognize
      ulceration from SIRT as a potential complication of treatment. The characteristic
      endoscopic, radiologic, and histopathologic findings are illustrated and
      recommendations are reviewed with regard to the current literature.

PMID- 20693155
TI  - Pervasive horizontal transfer of rolling-circle transposons among animals.
AB  - Horizontal transfer (HT) of genes is known to be an important mechanism of
      genetic innovation, especially in prokaryotes. The impact of HT of transposable
      elements (TEs), however, has only recently begun to receive widespread attention
      and may be significant due to their mutagenic potential, inherent mobility, and
      abundance. Helitrons, also known as rolling-circle transposons, are a distinctive
      subclass of TE with a unique transposition mechanism. Here, we describe the first
      evidence for the repeated HT of four different families of Helitrons in an
      unprecedented array of organisms, including mammals, reptiles, fish,
      invertebrates, and insect viruses. The Helitrons present in these species have a
      patchy distribution and are closely related (80-98% sequence identity), despite
      the deep divergence times among hosts. Multiple lines of evidence indicate the
      extreme conservation of sequence identity is not due to selection, including the
      highly fragmented nature of the Helitrons identified and the lack of any
      signatures of selection at the nucleotide level. The presence of horizontally
      transferred Helitrons in insect viruses, in particular, suggests that this may
      represent a potential mechanism of transfer in some taxa. Unlike genes, Helitrons
      that have horizontally transferred into new host genomes can amplify, in some
      cases reaching up to several hundred copies and representing a substantial
      fraction of the genome. Because Helitrons are known to frequently capture and
      amplify gene fragments, HT of this unique group of DNA transposons could lead to
      horizontal gene transfer and incur dramatic shifts in the trajectory of genome
      evolution.

PMID- 20693156
TI  - Chromosomal G + C content evolution in yeasts: systematic interspecies
      differences, and GC-poor troughs at centromeres.
AB  - The G + C content at synonymous codon positions (GC3s) in genes varies along
      chromosomes in most eukaryotes. In Saccharomyces cerevisiae, regions of high GC3s
      are correlated with recombination hot spots, probably due to biased gene
      conversion. Here we examined how GC3s differs among groups of related yeast
      species in the Saccharomyces and Candida clades. The chromosomal locations of
      GC3s peaks and troughs are conserved among four Saccharomyces species, but we
      find that there have been highly consistent small shifts in their GC3s values.
      For instance, 84% of all S. cerevisiae genes have a lower GC3s value than their
      S. bayanus orthologs. There are extensive interspecies differences in the Candida
      clade both in the median value of GC3s (ranging from 22% to 49%) and in the
      variance of GC3s among genes. In three species--Candida lusitaniae, Pichia
      stipitis, and Yarrowia lipolytica--there is one region on each chromosome in
      which GC3s is markedly reduced. We propose that these GC-poor troughs indicate
      the positions of centromeres because in Y. lipolytica they coincide with the five
      experimentally identified centromeres. In P. stipitis, the troughs contain
      clusters of the retrotransposon Tps5. Likewise, in Debaryomyces hansenii, there
      is one cluster of the retrotransposon Tdh5 per chromosome, and all these clusters
      are located in GC-poor troughs. Locally reduced G + C content around centromeres
      is consistent with a model in which G + C content correlates with recombination
      rate, and recombination is suppressed around centromeres, although the troughs
      are unexpectedly wide (100-300 kb).

PMID- 20693157
TI  - Lifibrol as a model compound for a novel lipid-lowering mechanism of action.
AB  - Lifibrol is a potent lipid-lowering drug with an unknown mechanism of action. We
      investigated its effects on lipoprotein and sterol metabolism in
      normocholesterolemic male participants. Seven participants were treated for 4
      weeks with 600 mg/d lifibrol and 9 with 40 mg/d pravastatin in a double-blind
      randomized parallel-group trial. Kinetic studies were performed at baseline and
      under acute and chronic treatment. Turnover of apolipoprotein B-100 was
      investigated with endogenous stable-isotope labeling, and kinetic parameters were
      derived by multicompartmental modeling. Lathosterol and cholesterol metabolism
      were investigated using mass isotopomer distribution analysis (MIDA) after [1
      (13)C]acetate labeling. Carbon metabolism was investigated by calculating the
      total isotope incorporation into newly formed sterols and measuring the disposal
      of acetate by (13)CO(2) breath analysis. Total- and low-density lipoprotein (LDL)
      cholesterol decreased by 18% and 27% under lifibrol and by 17% and 28% under
      pravastatin, respectively, whereas very-low-density lipoprotein (VLDL)
      cholesterol, triglycerides, and high-density lipoprotein (HDL) cholesterol did
      not change. Very-low-density lipoprotein apoB fractional synthesis and production
      increased under lifibrol but remained unchanged under pravastatin. Low-density
      lipoprotein apoB fractional synthesis and production increased under pravastatin
      but remained unchanged under lifibrol. Mass isotopomer distribution analysis
      indicated that both drugs decrease endogenous sterol synthesis after acute
      administration, but pravastatin had more powerful effects. Carbon-13 appearance
      in breath was higher during pravastatin than during lifibrol treatment. Mass
      isotopomer distribution analysis and carbon metabolism analysis indicated
      compartmentalization at the site of sterol synthesis, thus suggesting
      differential effects of the 2 drugs. Although having comparable lipid-lowering
      properties, lifibrol seems to have a mechanism of action distinct from that of
      statins. Lifibrol could serve as a model compound for the development of new
      lipid-lowering agents.

PMID- 20693158
TI  - Impact of increases in high-density lipoprotein cholesterol on cardiovascular
      outcomes during the armed forces regression study.
AB  - INTRODUCTION: high-density lipoprotein (HDL) cholesterol is a well-established
      inverse risk factor for cardiovascular disease. The extent to which
      cardiovascular risk can be modified through changes in HDL, however, is less
      clear. We further examined the role of aggressive HDL raising therapy on
      cardiovascular outcomes in the 143 patients enrolled in the Armed Forces
      Regression Study (AFREGS). METHODS: reanalysis of the AFREGS population. Patients
      with stable coronary disease were randomized to receive gemfibrozil, niacin, and
      cholestyramine in combination or matching placebos, on top of aggressive dietary
      and exercise modification for a 30-month period. Blood work was performed at
      baseline and repeated after 1 year of therapy. RESULTS: patients were divided
      into 3 groups based on their therapeutic response: no HDL increase, mild HDL
      increase, and large HDL increase (% change in HDL <= 0, <= the lower 2 tertiles
      of HDL increase, and > the upper tertile of HDL increase, respectively). A
      progressive decrease in cardiovascular events was noted across these groups
      (30.4%, 19.4%, and 3.2%, respectively, P = .01). Kaplan-Meier analysis according
      to percentage change in HDL demonstrated a similar improvement in event-free
      survival (P = .01). Proportional hazards modeling also demonstrated that
      increasing HDL predicted a lower hazard of cardiovascular events, even after
      adjusting for changes in low-density lipoprotein ([LDL] P < .01). For every 1%
      increase in HDL achieved, a 2% decrease in events was recognized. CONCLUSIONS:
      these data suggest that in a population of patients with stable atherosclerosis,
      the greater the percentage increase in HDL achieved, the greater the
      cardioprotective benefit. This further supports HDL raising as a beneficial
      therapeutic strategy.

PMID- 20693159
TI  - Both mitochondrial KATP channel opening and sarcolemmal KATP channel blockage
      confer protection against ischemia/reperfusion-induced arrhythmia in anesthetized
      male rats.
AB  - AIM: this study was performed to assess the effect of selective sarcolemmal
      adenosine triphosphate (ATP)-sensitive K(+) channel (K(ATP)) inhibition and the
      mitochondrial K(ATP) channel activation on ischemia and reperfusion (I/R)-induced
      arrhythmias in different gender of rats. We compared the effect of a selective
      sarcolemmal K(ATP) channel blocker HMR 1098, a selective mitochondrial K(ATP)
      channel opener diazoxide, a nonselective K(ATP) channel opener pinacidil, and the
      combination of pinacidil with HMR 1098 on the incidence and duration of
      ventricular arrhythmias in 2 groups: anesthetized males (n = 31) and females (n =
      31). MAIN METHODS: ischemia and reperfusion was produced by occluding the left
      main coronary artery of Sprague-Dowley rats for 6 minutes followed by re-opening
      of the artery for 6 minutes. KEY FINDINGS: the arrhythmia score and the duration
      of arrhythmias were significantly reduced by HMR 1098, diazoxide, and pinacidil
      in male rats. The combination of the pinacidil with HMR 1098 did not change the
      antiarrhythmic effect of pinacidil. The duration of arrhythmas was shorter in
      females than that in the corresponding males. Drug treatments were not effective
      in decreasing arrhythmias in female groups to the same extent as in the male
      group. However, the mitochondrial K( ATP) channel activation that is provided by
      the combination of pinacidil with HMR 1098 significantly decreased the total
      length of arrhythmias in females. SIGNIFICANCE: results of the current study
      indicate that both mitochondrial K(ATP) channel activation and sarcolemmal K(ATP)
      channel inhibition exert antiarrhythmic action in male rats. The antiarrhythmic
      effect of pinacidil is not depend on the sarcolemmal K(ATP) channel opening.
      These results also indicate that K(ATP) channel modulators show no discernable
      effect in female rats due to the already low incidence of arrhythmias in females.

PMID- 20693160
TI  - Kidney dysfunction during lenalidomide treatment for AL amyloidosis.
AB  - BACKGROUND: Lenalidomide is an immunomodulatory agent used to treat plasma cell
      dyscrasias. We previously observed worsening of kidney function in a high
      proportion of patients with AL amyloidosis during lenalidomide treatment. The
      objective of this study is to characterize alterations in kidney function among
      patients with AL amyloidosis undergoing treatment with lenalidomide. METHODS:
      This is a secondary analysis of an ongoing clinical trial at a single referral
      centre. Forty-one patients with AL amyloidosis received lenalidomide with or
      without dexamethasone in monthly cycles. Kidney dysfunction was defined as >= 50%
      increase in serum creatinine. Severe kidney dysfunction was defined as >= 100%
      increase in serum creatinine. Recovery of renal function was defined as a return
      of serum creatinine to within 25% of the pre-treatment value or discontinuation
      of dialysis. RESULTS: Twenty-seven of 41 patients (66%) developed kidney
      dysfunction during lenalidomide treatment. The kidney dysfunction was severe in
      13 of these patients (32%); four of whom required initiation of dialysis (10%).
      The median time to kidney dysfunction after starting lenalidomide was 44 days
      (interquartile range 15-108 days). Four of eight patients without underlying
      renal amyloidosis developed kidney dysfunction. Patients with severe kidney
      dysfunction were older and had a higher frequency of underlying renal
      amyloidosis, greater urinary protein excretion, and lower serum albumin. Recovery
      of renal function occurred in 12 patients (44%). CONCLUSIONS: Among patients with
      AL amyloidosis, worsening of kidney function occurs frequently during
      lenalidomide treatment. While a causal role of the drug has not been established,
      our findings suggest that kidney function should be monitored closely during
      treatment with this drug.

PMID- 20693161
TI  - Roles of PDGF receptor-beta in the structure and function of postnatal kidney
      glomerulus.
AB  - BACKGROUND: Mesangial cell functions are critically regulated by platelet-derived
      growth factor receptor (PDGFR)-beta signals. In contrast to the well-established
      role of PDGFR-beta in the development of kidney glomerulus, its role in adult
      kidney glomerulus remains controversial. METHODS: We deleted the PDGFR-beta gene
      postnatally using the Cre-loxP system and analysed the long-term effects of PDGFR
      beta inhibition on glomerular changes associated with ageing and subtotal
      nephrectomy. RESULTS: Mice depleted of PDGFR-beta (Deletant) survived without
      showing apparent abnormalities. In glomerulus of Deletant, mesangial PDGFR-beta
      expression was decreased. The glomerular cell numbers were low, and the ageing
      associated increment of mesangial matrix area was suppressed in Deletant as
      compared with control mice with conserved PDGFR-beta expression (Floxed) at 48
      weeks of age. At 2 weeks after subtotal nephrectomy, albuminuria and the
      elevation of blood urea nitrogen were aggravated in Deletant. At this time,
      Deletant showed specific glomerular changes that included many hypertrophic
      podocytes and collapsed capillaries. At 12 weeks after subtotal nephrectomy, the
      kidney function in Deletant restored to the level of Floxed; however, the
      Deletant glomeruli showed dilated capillaries, decreased cell number and reduced
      mesangial matrix area with less extended mesangial cell processes as compared
      with Floxed. CONCLUSIONS: The long-term inhibition of mesangial PDGFR-beta
      prevented age-related mesangial expansion. On the other hand, the kidney
      glomeruli with decreased PDGFR-beta showed increased vulnerability to the acute
      nephron loss, and showed mesangial insufficiency in the following adaptive
      process.

PMID- 20693162
TI  - Mast cell chymase inhibition reduces atherosclerotic plaque progression and
      improves plaque stability in ApoE-/- mice.
AB  - AIMS: mast cells have been shown to accumulate in the adventitia of human
      atherosclerotic plaques and were recently demonstrated by us to contribute to
      plaque progression and instability. In this study, we investigated whether
      selective inhibition of mast cell chymases would affect the lesion development
      and stability. METHODS AND RESULTS: the protease inhibitor RO5066852 appeared to
      be a potent inhibitor of chymase activity in vitro and ex vivo. With this
      inhibitor, we provide three lines of evidence that chymase inhibition can prevent
      many pro-atherogenic activities. First, oral administration of RO5066852 reduced
      spontaneous atherosclerosis in the thoracic aorta of apoE(-/-) mice. Second,
      chymase inhibition prevented the accelerated plaque progression observed in apoE(
      /-) mice that were exposed to repetitive episodes of systemic mast cell
      activation. Furthermore, RO5066852 enhanced lesional collagen content and reduced
      necrotic core size. Third, RO5066852 treatment almost completely normalized the
      increased frequency and size of intraplaque haemorrhages observed in apoE(-/-)
      mice after acute perivascular mast cell activation in advanced atherosclerosis.
      CONCLUSION: our data indicate that chymase inhibition can inhibit pro-atherogenic
      and plaque destabilizing effects which are associated with perivascular mast cell
      activation. Our study thus identifies pharmacological chymase inhibition as a
      potential therapeutic modality for atherosclerotic plaque stabilization.

PMID- 20693163
TI  - The TRIB3 R84 variant is associated with increased carotid intima-media thickness
      in vivo and with enhanced MAPK signalling in human endothelial cells.
AB  - AIMS: TRIB3, a mammalian tribbles homologue, affects insulin signalling and
      action by inhibiting Akt phosphorylation. A TRIB3 Q84R gain-of-function
      polymorphism has been associated with insulin resistance both in vitro and in
      vivo and with several atherosclerotic phenotypes, including increased carotid
      intima-media thickness (IMT). We wanted to replicate this latter association and,
      if so, to get deeper insights about the molecular mechanisms underlying the role
      of the TRIB3 Q84R polymorphism in atherosclerosis. METHODS AND RESULTS: in 430
      Caucasians of European ancestry, carotid IMT was increased in QR (n = 116) and RR
      (n = 15) when compared with QQ (n = 299) subjects (P= 0.009), thus replicating
      similar data recently obtained among Asians. In human umbilical vein endothelial
      cells (HUVECs) naturally carrying the QQ genotype, 24 h insulin stimulation
      increased monocyte adhesion, vascular cell adhesion molecule-1 (VCAM-1) and
      intercellular adhesion molecule-1 (ICAM-1) expression, and mitogen-activated
      protein kinase (MAPK) kinase (MEK)-MAPK activation. Conversely, QR- and RR-HUVECs
      had increased unstimulated monocyte adhesion, VCAM-1 and ICAM-1 expression, and
      MEK-MAPK activation which did not increase further upon insulin stimulation. In
      addition, QQ-, QR-, and RR-HUVECs showed similar basal Akt phosphorylation and
      nitric oxide synthase activity which, however, were significantly increased by
      insulin only in QQ cells. CONCLUSION: the TRIB3 R4 variant is associated with
      increased carotid IMT also in Caucasians, thus replicating previous data obtained
      in Asians. In addition, in HUVECs, this variant is associated with unbalanced
      insulin signalling. This abnormality may favour vasoreactivity, intima-media
      thickening, and plaque formation and may, therefore, underlie the deleterious
      role exerted by the variant on the susceptibility to atherosclerosis.

PMID- 20693164
TI  - Mitochondrial metabolism revisited: a route to cardioprotection.

PMID- 20693165
TI  - Alpha-receptor blockade improves muscle perfusion and glucose uptake in heart
      failure.
AB  - AIMS: Alpha-adrenergic receptor-mediated vasoconstriction might underlie the
      insulin resistance seen in conditions associated with increased sympathetic tone,
      like chronic heart failure (CHF). Alpha-adrenergic receptor blockade by
      phentolamine could improve forearm blood flow (FBF) and forearm glucose uptake
      (FGU) in CHF patients. METHODS AND RESULTS: In 8 CHF patients and in 12 healthy
      volunteers, FBF (plethysmography) and FGU were measured in both forearms during a
      150 min hyperinsulinaemic euglycaemic clamp procedure. During the final 30 min of
      the clamp, phentolamine was infused into one arm (experimental arm) at a dose of
      5.0 MUg; min(-1) dL(-1) of forearm volume. Insulin infusion (t = 0-120 min)
      increased FGU in the two groups, without affecting FBF. In the CHF group, alpha
      adrenergic receptor blockade by phentolamine (t = 120-150 min) further increased
      FGU in the experimental arm from 3.0 +/- 0.7 to 5.0 +/- 0.9 MUmol min(-1) dL(-1)
      (P = 0.03). Forearm glucose uptake in the contralateral forearm remained
      unchanged. In the control group, phentolamine infusion did not increase FGU in
      the experimental forearm. The increase in blood flow in response to phentolamine
      was similar in both groups (CHF: 2.1 +/- 0.3-7.5 +/- 1.7 mL min(-1) dL(-1), P <
      0.001; controls 1.5 +/- 0.2-5.5 +/- 0.8 mL min(-1) dL(-1), P < 0.001 for both,
      CHF vs. control, P = 0.2). Phentolamine did not affect FBF in the control arm in
      either group. CONCLUSION: Alpha-adrenergic receptor blockade improves FGU in CHF
      patients. As the increase in FBF is similar in controls and CHF patients, this
      might be explained by an improved glucose-extraction capacity in CHF patients.

PMID- 20693166
TI  - The European Journal of Heart Failure in 2010: current impact factor, time-to
      first decision, and number of submissions.

PMID- 20693168
TI  - Recurrent pericarditis caused by transdiaphragmatic migration of surgical tacks.

PMID- 20693167
TI  - A new avenue to cure cancer by turning adaptive immune T cells to innate immune
      NK cells via reprogramming.
AB  - Thymocytes after T-lineage commitment develop in the T-cell pathway. However, in
      a recent study, Li et al. (2010) demonstrated that inducing to delete Bcl11b gene
      in these thymocytes, even in mature T cells turns these cells into natural killer
      (NK) cells during the culture. They called this conversion 'reprogramming', and
      the reprogrammed killer cells 'ITNK cells'. The ITNK cells possessed tumor-killer
      ability and did not indiscriminately kill normal cells. This exciting finding
      represents a major breakthrough towards curing cancer and identifies an
      important, novel transcription factor in the thymus development.

PMID- 20693169
TI  - Determinants and prognostic value of pulmonary arterial pressure in patients with
      chronic heart failure.
AB  - AIMS: The epidemiology of pulmonary arterial hypertension (PAH) in patients with
      heart failure (HF) is poorly described. Our aim was to investigate the
      determinants and prognostic significance of PAH in a large representative
      outpatient population with HF. METHODS AND RESULTS: Routine measurement of right
      ventricular tricuspid pressure gradient (RVTG) was attempted among unselected,
      consecutive referrals to an HF clinic. The diagnosis of HF was based on symptoms,
      signs, echocardiography, and N-terminal pro-brain natriuretic peptide (NT
      proBNP). Of 2100 patients referred, 1380 were diagnosed as HF, of whom 1026 had
      left ventricular systolic dysfunction (LVSD) and 354 did not. Right ventricular
      tricuspid pressure gradient could be measured in 270 (26%) patients with and 143
      (40%) without LVSD. The highest RVTG quartile [RVTG > 35 mmHg equivalent to an
      estimated PA systolic pressure (PASP) > 45 mmHg] constituted 7% of all those with
      HF and was associated with higher LV filling pressures, LV end-diastolic volume,
      LVSD, and more severe mitral regurgitation (MR). During a median (inter-quartile
      range) follow-up of 66 (56-74) months, mortality was 40.3%. Mortality was similar
      in the lowest quartile of RVTG and in those in whom RVTG could not be measured
      and rose with increasing RVTG quartile (log-rank: 26.9; P < 0.0001). The highest
      RVTG quartile, age, blood pressure, and log NT-proBNP independently predicted
      mortality. Right ventricular tricuspid pressure gradient >35 mmHg had a 96%
      specificity to discriminate between those with and without HF in patients without
      LVSD. CONCLUSION: Using a definition of PASP > 45 mmHg, 7% of the patients with
      HF have PAH, which is associated with worse LV function, MR, and prognosis.
      Whether PAH is a target for therapy in this population remains to be elucidated.

PMID- 20693170
TI  - Subaortic membrane: correlation of imaging with pathology.

PMID- 20693171
TI  - Right ventricular thrombus and pulmonary embolism in patient with anterior
      myocardial infarction.

PMID- 20693172
TI  - The potent bactericidal activity of streptomycin in the guinea pig model of
      tuberculosis ceases due to the presence of persisters.
AB  - OBJECTIVES: The biphasic kill curve of isoniazid against Mycobacterium
      tuberculosis in guinea pigs is due to the presence of persisters rather than
      selection of isoniazid-resistant mutants. To determine whether this phenomenon is
      common to other bactericidal drugs, we studied the activity of streptomycin and
      its ability to select for streptomycin-resistant mutants in the guinea pig model
      of tuberculosis. METHODS: Pharmacokinetic studies were performed to establish the
      human-equivalent dose of streptomycin. Guinea pigs were aerosol-infected with M.
      tuberculosis and 2 weeks later streptomycin was given for 5 days/week via
      intramuscular injection. Bactericidal activity was assessed by homogenizing and
      plating lungs for cfu until 10 weeks of treatment. At each timepoint, cfu were
      isolated, suspended in normal saline and re-plated on plates containing 0.5, 1.0,
      2.0 or 10.0 mg/L streptomycin. RESULTS: The human-equivalent dose of streptomycin
      was determined to be 70 mg/kg. Streptomycin showed potent activity during the
      first 14 days of treatment, rescuing all animals from acute tuberculosis-related
      death and reducing lung cfu by ~4 log(10). However, streptomycin activity was
      dramatically reduced thereafter, as lung cfu declined by only ~1 log(10) over the
      next 56 days of treatment. Although streptomycin-resistant mutants were
      detectable, their frequency of isolation was identical at treatment initiation
      and after 70 days of treatment. CONCLUSIONS: The reduced activity of streptomycin
      during the second phase of monotherapy is not associated with the selection of
      streptomycin-resistant mutants but, rather, with the presence of phenotypically
      tolerant 'persisters'.

PMID- 20693173
TI  - Cephalosporin MIC creep among gonococci: time for a pharmacodynamic rethink?
AB  - BACKGROUND: Gonorrhoea has been among the easiest infections to cure with
      antibiotics. Nevertheless, emerging resistance has driven repeated treatment
      shifts. Decreased cephalosporin susceptibility is now being reported. We examined
      cephalosporin MIC trends for Neisseria gonorrhoeae in the UK and undertook
      pharmacodynamic analyses to predict efficacy against strains with raised MICs.
      METHODS: Neisseria gonorrhoeae isolates were collected annually in a structured
      surveillance from 26 genitourinary medicine clinics in England and Wales. MICs
      were determined by agar dilution and confirmed by Etests. Pharmacodynamic
      modelling was performed for cefixime and ceftriaxone with Monte Carlo
      simulations. RESULTS: There was a progressive emergence of small numbers of
      gonococci with cephalosporin MICs of 0.125-0.25 mg/L; these were not seen before
      2005 but, for ceftriaxone and cefixime, respectively, accounted for 0.4% (95%
      confidence interval 0.2%-1.1%) and 2.8% (1.6%-4.8%) of the 1253 isolates
      collected in 2008; such MICs are 16-64 times the modal values for the species.
      Pharmacodynamic analysis was complicated by evidence that cephalosporins need a
      longer period with the free drug level above MIC than the 7-10 h required for
      penicillin G; nevertheless, pharmacodynamic analyses predict that failures with
      the standard 400 mg cefixime po and 250 mg ceftriaxone im regimens become likely
      around the present MIC maxima. CONCLUSIONS: Gonococci with ceftriaxone and
      cefixime MICs of 0.125-0.25 mg/L are accumulating in the UK. These MICs lie on
      the edge of likely responsiveness to current regimens, which need review.
      Possible responses include: (i) higher cephalosporin doses; (ii) multidose
      cephalosporin regimens; (iii) multidrug regimens; (iv) microbiologically directed
      treatment; or, in the future, (v) drug cycling. The practicalities of these
      approaches are discussed.

PMID- 20693174
TI  - Pharmacodynamic effect of clinical vancomycin exposures on cell wall thickness in
      heterogeneous vancomycin-intermediate Staphylococcus aureus.
AB  - OBJECTIVES: Heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA)
      have a higher predisposition to select for VISA with thickened cell walls upon
      vancomycin exposure, but the pharmacodynamic relationship of this occurrence with
      clinical doses is unknown. This study investigates the impact of clinical
      vancomycin dose simulations on cell wall thickness (CWT) and the emergence of
      resistance in hVISA in an in vitro pharmacodynamic model. METHODS: In an in vitro
      pharmacokinetic/pharmacodynamic model, we simulated 125-2000 mg of vancomycin
      every 12 h (fAUC/MIC 24-225) over a 72 h period against three clinical hVISA and
      two standard control S. aureus strains. Pharmacodynamic activity, susceptibility
      and resistance populations were assessed, and CWT was determined at the end of
      the exposure. RESULTS: Bactericidal activity occurred in hVISA only with
      vancomycin fAUC/MIC >= 164 exposures, but regrowth occurred after 24 h,
      regardless of initial activity. Following vancomycin exposure, CWT correlated
      with MIC increases (r = 0.66; P  < 0.0001). A significant increase in CWT
      occurred in hVISA with any vancomycin simulation, including the high-dose
      fAUC/MIC 225 regimen (24.4% increase in hVISA versus 3.3% with control; P <
      0.001). Any vancomycin exposure in two of the three hVISA strains resulted in
      isolates with MICs >= 3 mg/L and as high as 8 mg/L, which corresponded with a
      more resistant VISA population profile. CONCLUSIONS: High-dose vancomycin
      exposures in hVISA cannot prevent cell wall thickening, but prudent therapeutic
      strategies including treatment doses >= 1500 mg every 12 h (AUC/MIC >= 364) in
      conjunction with avoidance of long-term vancomycin exposure may avert further
      reduced susceptibility.

PMID- 20693175
TI  - Effect of site of lactate infusion on regional lactate exchange in pigs.
AB  - BACKGROUND: The rate of extra-hepatic lactate production and the route of influx
      of lactate to the liver may influence both hepatic and extra-hepatic lactate
      exchange. We assessed the dose-response of hepatic and extra-hepatic lactate
      exchange during portal and central venous lactate infusion. METHODS: Eighteen
      pigs randomly received either portal (n=5) or central venous (n=7) lactate
      infusion or saline (n=6). Sodium lactate was infused at 33, 66, 99, and 133 umol
      kg-1 min-1 for 20 min each. Systemic and regional abdominal blood flows and
      plasma lactate were measured at 20 min intervals until 1 h post-infusion, and
      regional lactate exchange was calculated (area under lactate uptake-time curve).
      RESULTS: Total hepatic lactate uptake [median (95% confidence interval)] during
      the experimental protocol (140 min) was higher during portal [8198 (5487-12 798)
      umol kg(-1)] than during central venous lactate infusion [4530 (3903-5514) umol
      kg-1, P<0.05]. At a similar hepatic lactate delivery (~400 umol kg-1 min-1),
      hepatic lactate uptake [mean and standard deviation (sd)] was higher during
      portal [118 (sd 55) umol kg-1 min-1] than during central venous lactate infusion
      [44 (12) umol kg-1 min-1, P < 0.05]. Time courses of arterial lactate
      concentrations and lactate uptake at other measured regions were similar in both
      groups. CONCLUSIONS: Higher hepatic lactate uptake during portal compared with
      central venous lactate infusion at a similar total hepatic lactate influx
      underlines the role of portal vein lactate concentration in total hepatic lactate
      uptake capacity. Arterial lactate concentration does not depend on the site of
      lactate infusion. At higher arterial lactate concentrations, all regions
      participated in lactate uptake.

PMID- 20693176
TI  - Safety of glucose-containing solutions during accidental hyperinfusion in
      piglets.
AB  - BACKGROUND: Errors in fluid management can lead to significant morbidity in
      children. We conducted an experimental animal study to determine the margin of
      safety in accidental hyperinfusion of different glucose and electrolyte
      containing solutions. METHODS: Fifteen piglets [bodyweight 12.1 (sd 2.0) kg] were
      randomly assigned to receive either 100 ml kg-1 of balanced electrolyte solution
      with glucose 1% (BS-G1), hypotonic electrolyte solution with glucose 5% (HE-G5),
      or glucose 40% solution (G40) over 1 h. Blood electrolytes, glucose, and
      osmolality and intracranial pressure (ICP) were measured before, during, and
      after fluid administration. RESULTS: Hyperinfusion of BS-G1 led to moderate
      hyperglycaemia [baseline 3.4 (sd 1.3) mmol litre-1, study end 12.6 (1.8) mmol
      litre-1], but no other relevant pathophysiological alterations. Hyperinfusion of
      HE-G5 produced marked hyperglycaemia [baseline 3.9 (1.2) mmol litre-1, study end
      48.6 (4.3) mmol litre-1, P < 0.05] and hyponatraemia [baseline 136.4 (1.3) mmol
      litre(-1), study end 119.6 (2.1) mmol litre-1, P < 0.05], whereas osmolality
      remained stable during the course of the study. Hyperinfusion of G40 induced
      acute hyperglycaemic/hyperosmolar decompensation with an extreme decrease in
      serum electrolytes [e.g. sodium baseline 138 (1.1) mmol litre-1, 30 min 87.8
      (6.4) mmol litre-1, P < 0.01], leading to cardiac arrest after infusion of 50-75
      ml kg-1. ICP remained within a physiological range in all groups. CONCLUSIONS: In
      an animal model of accidental hyperinfusion, BS-G1 showed the widest margin of
      safety and can therefore be expected to enhance patient safety in perioperative
      fluid management in children; HE-G5 proved significantly less safe; and G40 was
      found to be outright hazardous.

PMID- 20693177
TI  - Ventilation-perfusion distributions and gas exchange during carbon dioxide
      pneumoperitoneum in a porcine model.
AB  - BACKGROUND: Carbon dioxide (CO2)-pneumoperitoneum (PP) of 12 mm Hg increases
      arterial oxygenation, but it also promotes collapse of dependent lung regions.
      This seeming paradox prompted the present animal study on the effects of PP on
      ventilation-perfusion distribution (V/Q) and gas exchange. METHODS: Fourteen
      anaesthetized pigs were studied. In seven pigs, single photon emission computed
      tomography (SPECT) was used for spatial analysis of ventilation and perfusion
      distributions, and in another seven pigs, multiple inert gas elimination
      technique (MIGET) was used for detailed analysis of V/Q matching. SPECT/MIGET and
      central haemodynamics and pulmonary gas exchange were recorded during anaesthesia
      before and 60 min after induction of PP. RESULTS: SPECT during PP showed no or
      only poorly ventilated regions in the dependent lung compared with the
      ventilation distribution during anaesthesia before PP. PP was accompanied by
      redistribution of blood flow away from the non- or poorly ventilated regions. V/Q
      analysis by MIGET showed decreased shunt from 9 (sd 2) to 7 (2)% after induction
      of PP (P<0.05). No regions of low V/Q were seen either before or during PP.
      Almost no regions of high V/Q developed during PP (1% of total ventilation).
      Pa(o2) increased from 33 (1.2) to 35.7 (3.2) kPa (P<0.01) and arterial to end
      tidal Pco2 gradient (Pae'(co2) increased from 0.3 (0.1) to 0.6 (0.2) kPa
      (P<0.05). CONCLUSIONS: Perfusion was redistributed away from dorsal, collapsed
      lung regions when PP was established. This resulted in a better V/Q match. A
      possible mechanism is enhanced hypoxic pulmonary vasoconstriction.

PMID- 20693178
TI  - Ischaemic and morphine-induced post-conditioning: impact of mK(Ca) channels.
AB  - BACKGROUND: Mitochondrial calcium-sensitive potassium (mK(Ca)) channels are
      involved in cardiac preconditioning. In the present study, we investigated
      whether also ischaemic-, morphine-induced post-conditioning, or both is mediated
      by the activation of mK(Ca) channels in the rat heart in vitro. METHODS: Animals
      were treated in compliance with institutional and national guidelines. Male
      Wistar rats were randomly assigned to one of seven groups (each n = 7). Control
      animals were not further treated. Post-conditioning was induced either by 3 * 30
      s of ischaemia/reperfusion (I-PostC) or by administration of morphine (M-PostC, 1
      uM) for 15 min at the onset of reperfusion. The mK(Ca)-channel inhibitor
      paxilline (1 uM) was given with and without post-conditioning interventions (M
      PostC+Pax, I-PostC+Pax, and Pax). As a positive control, we determined whether
      direct activation of mK(Ca) channels with NS1619 (10 uM) induced cardiac post
      conditioning (NS1619). Isolated hearts underwent 35 min ischaemia followed by 120
      min reperfusion. At the end of reperfusion, infarct sizes were measured by
      triphenyltetrazolium chloride staining. RESULTS: In the control group, infarct
      size was 53 (5)% of the area at risk. Morphine- and ischaemic post-conditioning
      reduced infarct size in the same range [M-PostC: 37 (4)%, I-PostC: 35 (5)%; each
      P<0.05 vs control]. The mK(Ca)-channel inhibitor paxilline completely blocked
      post-conditioning [M-PostC+Pax: 47 (7)%, I-PostC+Pax: 51 (3)%; each P<0.05 vs M
      PostC and I-PostC, respectively]. Paxilline itself had no effect on infarct size
      (NS vs control). NS1619 reduced infarct size to 33 (4)% (P < 0.05 vs control).
      CONCLUSIONS: Ischaemic- and morphine-induced post-conditioning is mediated by the
      activation of mK(Ca) channels.

PMID- 20693179
TI  - Development and longitudinal validation of the overall benefit of analgesia
      score: a simple multi-dimensional quality assessment instrument.
AB  - BACKGROUND: The goal of this study was to develop and validate the overall
      benefit of analgesic score (OBAS), which assesses pain intensity and the opioid
      related adverse effects. METHODS: The score was developed and validated in four
      trials (n=1470 patients). Data from randomized trial I were used to develop the
      OBAS (factor analysis). Data from randomized trial II were used to compare the
      resolution of rofecoxib's analgesic effects between OBAS and pain scores.
      Randomized trial III (spine surgery) was conducted to evaluate prospectively the
      reliability of the OBAS and to compare its resolution of analgesic treatment with
      the opioid-related symptom distress scale (OR-SDS) and the modified brief pain
      inventory short form (m-BPI-sf). Trial IV was conducted to evaluate in patients
      with a moderate-to-high level of postoperative pain (after major abdominal
      surgery) the relation of OBAS and pain scores for patients' satisfaction with
      analgesic therapy. RESULTS: The seven-item OBAS yielded a higher resolution of
      analgesic treatment effects than pain scores, the OR-SDS and m-BPI-sf. The OBAS
      has a fair inter-rater reliability (concordance correlation of 0.71 c) and is
      more sensitive (P=0.03) in indicating the delivery of opioid boluses than the
      dedicated OR-SDS. The OBAS, but not pain scores at rest or pain scores during
      movement, explained significant variance in patients' satisfaction with
      postoperative pain therapy. CONCLUSIONS: The OBAS is a simple, multi-dimensional
      quality assessment instrument to measure patients' benefit from postoperative
      pain therapy. Opioid symptom distress, pain relief, and patients' satisfaction
      are combined in a reliable and valid tool.

PMID- 20693180
TI  - Expressiveness of global coagulation parameters in dilutional coagulopathy.
AB  - BACKGROUND: Plasma-free volume replacement in haemorrhage often results in
      dilutional coagulopathy. Prothrombin time index (PTI) and activated partial
      thromboplastin time (aPTT) are used for monitoring haemostasis but have not yet
      been clinically evaluated. Our aim was to investigate the effects of
      haemodilution on the course of global coagulation tests and clotting factors
      (CFs). METHODS: Blood samples from each of 10 volunteers were diluted with sodium
      chloride 0.9% (saline) or 6% hydroxyethyl starch 130/0.4 (HAES) by 30-80%. PTI,
      aPTT, CF, and the thrombelastometric parameters (ROTEM((r))) coagulation time
      (CT) and maximum clot firmness (MCF) were determined. RESULTS: Dilution-dependent
      CF decreased in an almost linear manner and was not influenced by the diluent.
      Critically low activities for CF of ~30% and a fibrinogen concentration <100 mg
      dl(-1) were measured at dilutions of between 60% and 75%. Critically low CF
      activities of about 30% were indicated by a PTI of 35-40%. PTI and MCF decreased
      continuously, demonstrating a good correlation with CF activities and fibrinogen.
      aPTT and CT showed a linear course up to a dilution of 65-75% corresponding to CF
      activities of 30-40%. Thereafter, values became pathological. PTI and aPTT were
      not influenced by the type of diluent, whereas the diluents had profound
      differences on results of thromboelastometry. CONCLUSIONS: PTI and MCF are useful
      for monitoring dilution and intervention points. aPTT and CT reflect intervention
      points when showing pathological values. The type of diluents does not seem to
      interfere with PTI and aPTT, but HAES impairs haemostasis in ROTEM((r)) more
      profoundly than saline.

PMID- 20693181
TI  - Continuous non-invasive finger arterial pressure monitoring reflects intra
      arterial pressure changes in children undergoing cardiac surgery.
AB  - BACKGROUND: Continuous non-invasive measurement of finger arterial pressure (FAP)
      is a reliable technology in adults. FAP is measured with an inflatable cuff
      around the finger and simultaneously converted to a reconstructed brachial artery
      pressure waveform (reBAP) by the NexfinTM device. We assessed the adequacy of a
      prototype device (Nexfin-paediatric), designed for a paediatric population, for
      detecting rapid arterial pressure changes in children during cardiac surgery.
      METHODS: Thirteen anaesthetized children with a median age of 11 months (2 months
      7 yr) undergoing congenital cardiac surgery were included in the study. reBAP and
      intra-arterial pressure (IAP) were recorded simultaneously during the surgical
      procedure. To assess the accuracy of reBAP in tracking arterial pressure changes,
      the four largest IAP variations within a 5 min time interval were identified from
      each procedure. These variations were compared offline with reBAP during a 10 s
      control period before and a 10 s period after an arterial pressure change had
      occurred. RESULTS: In 10 out of 13 children, a non-invasive arterial pressure
      recording could be obtained. Therefore, recordings from these 10 children were
      eligible for further analysis, resulting in 40 data points. The correlation
      coefficient between reBAP and IAP in tracking mean arterial pressure (MAP)
      changes was 0.98. reBAP followed changes in IAP with a mean bias for systolic,
      diastolic arterial pressure, and MAP of 0.0 mm Hg (sd 5.8), 0.1 (sd 2.8), and
      0.19 (sd 2.7), respectively. CONCLUSIONS: The prototype device closely follows
      arterial pressure changes in children. However, in a considerable number of
      attempts, obtaining a signal was time-consuming or unsuccessful. This technique
      seems promising but requires further technical development.

PMID- 20693182
TI  - Sevoflurane and propofol anaesthesia differentially modulate the effects of
      epinephrine and norepinephrine on microcirculatory gastric mucosal oxygenation.
AB  - BACKGROUND: Adequate gastrointestinal mucosal oxygenation is regarded to be
      crucial in the prevention and therapy of critical illness. Epinephrine and
      norepinephrine are used for perioperative haemodynamic support. However, their
      per se effects on gastromucosal haemoglobin oxygenation (MUHbO(2)) remain
      unclear. Moreover, respective effects of epinephrine and norepinephrine may be
      affected by the type of underlying anaesthesia. Thus, we studied the effects of
      epinephrine and norepinephrine during anaesthesia with sevoflurane or propofol on
      regional gastromucosal MUHbO(2) and systemic O(2)-derived variables. METHODS: In
      a double-randomized cross-over study, chronically instrumented dogs (n=6 per
      group) were anaesthetized randomly with sevoflurane or propofol, ventilated, and
      then randomly received either epinephrine or norepinephrine (0, 0.05, 0.1, and
      0.2 ug kg(-1) min(-1)). We measured gastromucosal MUHbO(2), systemic
      haemodynamics, and O(2)-derived variables. RESULTS: During sevoflurane
      anaesthesia, norepinephrine markedly increased MUHbO(2) (P<0.0001) and systemic
      oxygen transport (DO(2)) (P=0.0006). In contrast, epinephrine failed to increase
      MUHbO(2), despite doubling DO(2) (P=0.0002). During propofol anaesthesia, in
      contrast to sevoflurane, neither epinephrine nor norepinephrine affected
      MUHbO(2), although epinephrine, but not norepinephrine, again resulted in
      markedly increased DO(2) (P<0.0001). CONCLUSIONS: The effects of epinephrine and
      norepinephrine depended on the type of anaesthesia. In addition, regional effects
      (i.e. MUHbO(2)) were not predictable from systemic effects (i.e. DO(2)).

PMID- 20693183
TI  - Apolipoprotein E genotype and mortality in Southern European and Anglo-Celt
      patients with type 2 diabetes: the Fremantle Diabetes Study.
AB  - OBJECTIVE: To determine whether cardiac and all-cause mortality are lower in
      Southern European (SE) patients than in Anglo-Celt (AC) patients with type 2
      diabetes in an urban Australian setting, and, if so, whether ethnicity-specific
      differences in apolipoprotein E (APOE) genotypes are contributory. DESIGN:
      Longitudinal observational cohort study. METHODS: We analysed detailed data from
      1057 patients from the community-based Fremantle Diabetes Study, 238 were of an
      SE migrant background and 819 of AC ethnicity. Cox proportional hazards modelling
      was used to identify independent predictors of cardiac and all-cause mortality.
      RESULTS: During 9.8+/-3.5 years of follow-up, 411 (38.9%) participants died, 161
      (39.2%) from cardiac causes. Significant positive baseline independent predictors
      of cardiac death were age, male gender, coronary heart disease, cerebrovascular
      disease, peripheral arterial disease, retinopathy and peripheral neuropathy
      (P<=0.004), while maternal history of diabetes was protective (P=0.014). After
      adjusting for these variables, APOE4 carriage was predictive (hazard ratio (95%
      confidence interval) 1.61 (1.01-2.58); P=0.048). SE ethnicity did not add
      significantly to the model either as a single variable or as an interaction term
      with APOE4 carriage (P>=0.86). Significant independent predictors of all-cause
      mortality were age, male gender, smoking, coronary heart disease, cerebrovascular
      disease, peripheral arterial disease, retinopathy, peripheral neuropathy and
      microalbuminuria (P<=0.047), while overweight/obesity, lipid-lowering therapy and
      recent exercise were protective (P<=0.008). APOE4 carriage, SE ethnicity and
      their interaction did not add to the model (P>=0.32). CONCLUSIONS: SE ethnicity
      does not confer an independent survival advantage in community-based Australian
      type 2 diabetic patients, but APOE4 carriers are at higher risk of cardiac death.

PMID- 20693184
TI  - Decision trees as a simple-to-use and reliable tool to identify individuals with
      impaired glucose metabolism or type 2 diabetes mellitus.
AB  - OBJECTIVE: The prevalence of unknown impaired fasting glucose (IFG), impaired
      glucose tolerance (IGT), or type 2 diabetes mellitus (T2DM) is high. Numerous
      studies demonstrated that IFG, IGT, or T2DM are associated with increased
      cardiovascular risk, therefore an improved identification strategy would be
      desirable. The objective of this study was to create a simple and reliable tool
      to identify individuals with impaired glucose metabolism (IGM). DESIGN AND
      METHODS: A cohort of 1737 individuals (1055 controls, 682 with previously unknown
      IGM) was screened by 75 g oral glucose tolerance test (OGTT). Supervised machine
      learning was used to automatically generate decision trees to identify
      individuals with IGM. To evaluate the accuracy of identification, a tenfold cross
      validation was performed. Resulting trees were subsequently re-evaluated in a
      second, independent cohort of 1998 individuals (1253 controls, 745 unknown IGM).
      RESULTS: A clinical decision tree included age and systolic blood pressure
      (sensitivity 89.3%, specificity 37.4%, and positive predictive value (PPV)
      48.0%), while a tree based on clinical and laboratory data included fasting
      glucose and systolic blood pressure (sensitivity 89.7%, specificity 54.6%, and
      PPV 56.2%). The inclusion of additional parameters did not improve test quality.
      The external validation approach confirmed the presented decision trees.
      CONCLUSION: We proposed a simple tool to identify individuals with existing IGM.
      From a practical perspective, fasting blood glucose and blood pressure
      measurements should be regularly measured in all individuals presenting in
      outpatient clinics. An OGTT appears to be useful only if the subjects are older
      than 48 years or show abnormalities in fasting glucose or blood pressure.

PMID- 20693185
TI  - Relationship of soil terrestrial radionuclide concentrations and the excess of
      lifetime cancer risk in western Mazandaran Province, Iran.
AB  - The main goal of this study is to lay out the map of the soil radionuclide
      activity concentrations and the terrestrial outdoor gamma dose rates in the
      western Mazandaran Province of Iran, and to present an evaluation scheme.
      Mazandaran Province was selected due to its special geographical characteristics,
      high population density and the long terrestrial and aquatic borders with the
      neighbouring countries possessing nuclear facilities. A total of 54 topsoil
      samples were collected, ranging from the Nour to Ramsar regions, and were based
      on geological conditions, vegetation coverage and the sampling standards outlined
      by the International Atomic Energy Agency. The excess lifetime cancer risks
      (ELCRs) were evaluated and the coordinates of sampling locations were determined
      by the global positioning system. The average terrestrial outdoor gamma dose rate
      was 612.38 +/- 3707.93 nGy h(-1), at 1 m above the ground. The annual effective
      gamma dose at the western part of Mazandaran Province was 750 MUSv, and the ELCR
      was 0.26 * 10(-2). Soil samples were analysed by gamma spectrometry with a high
      purity germanium detector. The average (226)Ra, (232)Th, (40)K and (137)Cs
      activities were 1188.50 +/- 7838.40, 64.92 +/- 162.26, 545.10 +/- 139.42 and
      10.41 +/- 7.86 Bq kg(-1), respectively. The average soil radionuclide
      concentrations at the western part of Mazandaran Province were higher than the
      worldwide range. The excess lifetime risks of cancer and the annual effective
      gamma doses were also higher than the global average.

PMID- 20693186
TI  - Prospective alpha allocation in the Clarification of Optimal Anticoagulation
      through Genetics (COAG) trial.
AB  - BACKGROUND: The Clarification of Optimal Anticoagulation through Genetics (COAG)
      trial is a large, multicenter, double-blinded, randomized trial to determine
      whether use of a genotype-guided dosing algorithm (using clinical and genetic
      information) to initiate warfarin treatment will improve anticoagulation status
      when compared to a dosing algorithm using only clinical information. PURPOSE:
      This article describes prospective alpha allocation and balanced alpha allocation
      for the design of the COAG trial. METHODS: The trial involves two possibly
      heterogeneous populations, which can be distinguished by the difference in
      warfarin dose as predicted by the two algorithms. A statistical approach is
      detailed, which allows an overall comparison as well as a comparison of the
      primary endpoint in the subgroup for which sufficiently different doses are
      predicted by the two algorithms. Methods of allocating alpha for these analyses
      are given - a prospective alpha allocation and allocating alpha so that the two
      analyses have equal power, which we call a 'balanced alpha allocation.' RESULTS:
      We show how to include an analysis of the primary endpoint in a subgroup as a co
      primary analysis. Power can be improved by incorporating the correlation between
      the overall and subgroup analyses in a prospective alpha allocation approach.
      Balanced alpha allocation for the full cohort and subgroup tests to achieve the
      same desired power for both of the primary analyses is discussed in detail.
      LIMITATIONS: In the COAG trial, it is impractical to stratify the randomization
      on subgroup membership because genetic information may not be available at the
      time of randomization. If imbalances in the treatment arms in the subgroup are
      found, they will need to be addressed. CONCLUSIONS: The design of the COAG trial
      assures that the subgroup in which the largest treatment difference is expected
      is elevated to a co-primary analysis. Incorporating the correlation between the
      full cohort and the subgroup analyses provides an improvement in power for the
      subgroup comparison, and further improvement may be achieved via a balanced alpha
      allocation approach when the parameters involved in the sample size calculation
      are reasonably well estimated.

PMID- 20693187
TI  - Arsenic trioxide reduces 2,4,6-trinitrobenzene sulfonic acid-induced murine
      colitis via nuclear factor-kappaB down-regulation and caspase-3 activation.
AB  - Arsenic trioxide, As(2)O(3), already used in human anti-cancer therapy, is also
      an efficient agent against the autoimmune and inflammatory diseases developed in
      MRL/lpr mice. Inflammatory bowel diseases (IBDs), notably Crohn's disease, which
      remain without efficient treatment, display autoimmune and inflammatory
      components. We, therefore, hypothesized that As(2)O( 3) may be active on IBDs.
      Using the 2,4,6-trinitrobenzene sulfonic acid-induced murine model of colitis, we
      demonstrate that As(2)O(3) used either in a preventive or a curative mode
      markedly reduced the induced colitis as assessed by macroscopic and microscopic
      scores, leading to prolonged mice survival. In addition, As(2)O(3) was able to
      inhibit NF-kappaB expression and DNA-binding in colon extracts leading to
      decreased cytokine gene expression (i.e. tumor necrosis factor-alpha,
      interleukin(IL)-1beta, IL-12, IL-17, IL-18, and IL-23). Interestingly, As(2)O(3)
      also reduced keratinocyte-derived chemokine (KC), inducible nitric oxide synthase
      (iNOS) mRNA levels, and myeloperoxidase (MPO) protein expression suggesting an
      impairment of neutrophils. This was associated with a marked increase of
      procaspase-3 and induced caspase-3 activation. This caspase-3 co-localized with
      MPO in the remaining neutrophils suggesting that As(2)O( 3) might have eliminated
      inflamed cells probably by inducing their apoptosis. These results assessed the
      potent anti-inflammatory effect of As(2)O( 3), that targets both NF-kappaB and
      caspase-3 pathways, and suggests a therapeutic potential for Crohn's disease and
      other severe IBDs.

PMID- 20693188
TI  - Biobanking, consent, and commercialization in international genetics research:
      the Type 1 Diabetes Genetics Consortium.
AB  - BACKGROUND: and PURPOSE: This article describes several ethical, legal, and
      social issues typical of international genetics biobanking, as encountered in the
      Type 1 Diabetes Genetics Consortium (T1DGC). METHODS: By studying the examples
      set and lessons learned from other international biobanking studies and by
      devoting considerable time and resources to identifying, addressing, and
      continually monitoring ethical and regulatory concerns, T1DGC was able to
      minimize the problems reported by some earlier studies. CONCLUSIONS: Several
      important conclusions can be drawn based on the experience in this study: (1)
      Basic international standards for research ethics review and informed consent are
      broadly consistent across developed countries. (2) When consent forms are adapted
      locally and translated into different languages, discrepancies are inevitable and
      therefore require prompt central review and resolution before research is
      initiated. (3) Providing separate 'check-box' consent for different elements of a
      study creates confusion and may not be essential. (4) Creating immortalized cell
      lines to aid future research is broadly acceptable, both in the US and
      internationally. (5) Imposing some limits on the use of stored samples aids in
      obtaining ethics approvals worldwide. (6) Allowing potential commercial uses of
      donated samples is controversial in some Asian countries. (7) Obtaining
      government approvals can be labor-intensive and time-consuming, and can require
      legal and diplomatic skills.

PMID- 20693189
TI  - Measurement of islet cell antibodies in the Type 1 Diabetes Genetics Consortium:
      efforts to harmonize procedures among the laboratories.
AB  - BACKGROUND: and PURPOSE: Three network laboratories measured antibodies to islet
      autoantigens. Antibodies to glutamic acid decarboxylase (GAD65 [GADA]) and the
      intracellular portion of protein tyrosine phosphatase (IA-2(ic) [IA-2A]) were
      measured by similar, but not identical, methods in samples from participants in
      the Type 1 Diabetes Genetics Consortium (T1DGC). METHODS: All laboratories used
      radiobinding assays to detect antibodies to in vitro transcribed and translated
      antigen, but with different local standards, calibrated against the World Health
      Organization (WHO) reference reagent. Using a common method to calculate WHO
      units/mL, we compared results reported on samples included in the Diabetes
      Autoantibody Standardization Program (DASP), and developed standard methods for
      reporting in WHO units/mL. We evaluated intra-assay and inter-assay coefficient
      of variation (CV) in blind duplicate samples and assay comparability in four DASP
      workshops. RESULTS: Values were linearly related in the three laboratories for
      both GADA and IA-2A, and intra-assay technical errors for values within the
      standard curve were below 13% for GADA and below 8.5% for IA-2A. Correlations in
      samples tested 1-2 years apart were >97%. Over the course of the study, internal
      CVs were 10-20% with one exception, and the laboratories concordantly called
      samples GADA or IA-2A positive or negative in 96.7% and 99.6% of duplicates
      within the standard curve. Despite acceptable CVs and general concordance in
      ranking samples, the laboratories differed markedly in absolute values for GADA
      and IA-2A reported in WHO units/mL in DASP over a large range of values.
      LIMITATIONS: With three laboratories using different assay methods (including
      calibrators), consistent values among them could not be attained. CONCLUSIONS:
      Modifications in the assays are needed to improve comparability of results
      expressed as WHO units/mL across laboratories. It will be essential to retain
      high intra- and inter-assay precision, sensitivity and specificity and to confirm
      the accuracy of harmonized methods.

PMID- 20693192
TI  - Characteristics and risk factors for hyperglycemia in Chinese female patients
      with systemic lupus erythematosus.
AB  - The aim of the study was to investigate the characteristics and risk factors for
      hyperglycemia in Chinese female patients with systemic lupus erythematosus (SLE).
      One hundred and forty-six female SLE patients without a history of diabetes
      underwent a 75 g oral glucose tolerance test to evaluate glucose tolerance,
      insulin sensitivity and pancreatic beta cell function. According to the 1999
      World Health Organization criteria, all patients were divided into three groups:
      normal glucose regulation, impaired glucose tolerance and diabetes mellitus.
      Glucocorticoid doses, insulin sensitivity and pancreatic beta cell function were
      compared among these groups. Risk factors for hyperglycemia were analyzed by
      univariate and multi-variate regression analysis. Our results showed that 46 of
      the 146 female SLE patients (31.5 %) were hyperglycemic, including 21 (14.4%)
      diabetes mellitus patients and 25 (17.1%) impaired glucose tolerance patients.
      These female SLE patients with hyperglycemia were characterized by insulin
      resistance and reduced pancreatic beta cell function, and they were relatively
      young. Age >=35 years and high glucocorticoid doses were risk factors for
      hyperglycemia in Chinese female SLE patients. The prevalence of diabetes mellitus
      and impaired glucose tolerance are quite high in Chinese female SLE patients. It
      is suggested that plasma glucose concentration should be monitored regularly and
      oral glucose tolerance test should be recommended for SLE patients who have risk
      factors for hyperglycemia.

PMID- 20693193
TI  - Lupus erythematosus and the skin: a journey at times perplexing, usually complex,
      often challenging, and evermore exhilarating.

PMID- 20693194
TI  - The interferon-alpha signature of systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a prototypic multisystem autoimmune
      disorder where interplay of environmental and genetic risk factors leads to
      progressive loss of tolerance to nuclear antigens over time, finally culminating
      in clinical disease. The heterogeneity of clinical manifestations and the
      disease's unpredictable course characterized by flares and remissions are very
      likely a reflection of heterogeneity at the origin of disease, with a final
      common pathway leading to loss of tolerance to nuclear antigens. Impaired
      clearance of immune complexes and apoptotic material and production of
      autoantibodies have long been recognized as major pathogenic events in this
      disease. Over the past decade the type I interferon cytokine family has been
      postulated to play a central role in SLE pathogenesis, by promoting feedback
      loops progressively disrupting peripheral immune tolerance and driving disease
      activity. The identification of key molecules involved in the pathogenesis of SLE
      will not only improve our understanding of this complex disease, but also help to
      identify novel targets for biological intervention.

PMID- 20693195
TI  - Pathogenesis of cutaneous lupus erythematosus: common and different features in
      distinct subsets.
AB  - The term 'cutaneous lupus erythematosus' (CLE) comprises several related
      autoimmune skin disorders, defined as 'specific' skin manifestations of lupus
      erythematosus (LE). The spectrum of clinical presentation of CLE is wide,
      reaching from mild erythema to disseminated scarring skin lesions. There is
      increasing knowledge concerning the pathogenesis of LE skin lesions and it has
      been shown that a complex network of cutaneous cytokines, chemokines and adhesion
      molecules orchestrate and promote tissue injury observed in LE skin lesions.
      However, a complete understanding of the diverse pathophysiological mechanisms in
      the different CLE subsets does not exist. Here we review the main pathological
      features described in CLE patients against the background of the clinical
      diversity of different CLE subtypes.

PMID- 20693196
TI  - Cutaneous lupus erythematosus: recent lessons from animal models.
AB  - Cutaneous lupus erythematosus (CLE) may present as a clinically heterogeneous
      group of lupus-specific skin lesions that have common histopathological findings.
      Determination of the immunopathological sequence of events in this group of
      disorders has been challenging for dermatologists and immunologists but is vital
      for therapeutic targeting. We review animal models in which different aspects of
      immune alteration in CLE have been addressed. The MRL/lpr mouse develops
      spontaneous skin disease with some features of CLE. Study of this strain and
      related gene-manipulated strains has revealed roles for multiple cytokines,
      including interleukin (IL)-6, IL-18, and IL-21, in disease pathogenesis. A role
      for the growth factor colony stimulating factor 1 and the inflammatory protein
      high-mobility group box 1 has also been suggested. We discuss potential novel
      treatment options suggested by these models.

PMID- 20693197
TI  - Photosensitivity, phototesting, and photoprotection in cutaneous lupus
      erythematosus.
AB  - Cutaneous lupus erythematosus (CLE) is a heterogeneous autoimmune disease
      involving well-defined skin lesions that can be categorized as acute CLE (ACLE),
      subacute CLE (SCLE), chronic CLE (CCLE), or intermittent CLE (ICLE). It is
      commonly accepted that ultraviolet (UV) exposure can induce and exacerbate skin
      lesions in patients with certain subtypes of CLE. Phototesting with UVA and UVB
      irradiation using a standardized protocol has proven to be a reliable model to
      study photosensitivity in CLE and to analyse the underlying pathomechanisms of
      the disease. In addition to UV-mediated induction of apoptosis, the molecular and
      cellular factors that may underlie the abnormal long-lasting photoreactivity in
      CLE include mediators of inflammation such as cytokines and chemokines, inducible
      nitric oxide (NO) synthase (iNOS), and cellular adhesion molecules. The
      photosensitivity associated with CLE requires education of the patient about
      avoidance of excessive sun exposure, continuous photoprotection through physical
      measures such as protective clothing, and daily application of broad-spectrum
      sunscreens. Novel approaches to UV-protection, such as alpha-MSH or thymidine
      dinucleotides, might also have an impact on photosensitivity in patients with
      CLE. In this review, we summarize the current knowledge about photosensitivity in
      patients with CLE, including an overview of standardized phototesting procedures,
      possible molecular pathomechanisms, and photoprotection.

PMID- 20693198
TI  - The need to revisit the nosology of cutaneous lupus erythematosus: the current
      terminology and morphologic classification of cutaneous LE: difficult, incomplete
      and not always applicable.

PMID- 20693199
TI  - Overview of common, rare and atypical manifestations of cutaneous lupus
      erythematosus and histopathological correlates.
AB  - The skin is the second most frequently affected organ system in lupus
      erythematosus. Although only very rarely life threatening--an example is lupus
      erythematosus-associated toxic epidermal necrolysis--skin disease contributes
      disproportionally to disease burden in terms of personal and psychosocial
      wellbeing, vocational disability, and hence in medical and social costs. Since
      several manifestations are closely associated with the presence and activity of
      systemic lupus erythematosus, prompt and accurate diagnosis of cutaneous lupus
      erythematosus is essential. This review aims to cover common, rare, and atypical
      manifestations of lupus erythematosus-associated skin disease with a detailed
      discussion of histopathological correlates. Cutaneous lupus erythematosus covers
      a wide morphological spectrum well beyond acute, subacute and chronic cutaneous
      lupus erythematosus, which are commonly classified as lupus-specific skin
      disease. Other uncommon or less well-known manifestations include lupus
      erythematosus tumidus, lupus profundus, chilblain lupus, mucosal lupus
      erythematosus, and bullous lupus erythematosus. Vascular manifestations include
      leukocytoclastic and urticarial vasculitis, livedoid vasculopathy and livedo
      reticularis/ racemosa. Finally, we discuss rare presentations such as lupus
      erythematosus-related erythema exsudativum multiforme (Rowell syndrome), Kikuchi
      Fujimoto disease, extravascular necrotizing palisaded granulomatous dermatitis
      (Winkelmann granuloma), and neutrophilic urticarial dermatosis.

PMID- 20693200
TI  - Dermatological manifestations of Hughes' antiphospholipid antibody syndrome.
AB  - The dermatological manifestations of antiphospholipid syndrome (APS) may be the
      presenting features of APS syndrome. They are extremely diverse and
      heterogeneous, ranging from minor signs to life-threatening conditions such as
      widespread cutaneous necrosis. Their clinical significance is highly variable.
      Livedo reticularis is strongly associated with the arterial and microangiopathic
      subtypes of APS. Scientific data are required to determine the optimum management
      of these patients, who might benefit from recently developed antithrombotic
      agents.

PMID- 20693201
TI  - Involvement of scalp and nails in lupus erythematosus.
AB  - Lupus erythematosus (LE) is a systemic autoimmune disorder associated with
      polyclonal B-cell activation resulting in diverse patterns of autoantibody
      production and a heterogeneous clinical expression constituting a spectrum
      extending from limited cutaneous disease to life-threatening systemic
      manifestations. For daily clinical practice, the characteristics of cutaneous
      lupus erythematosus (CLE) have been well defined in terms of morphology, and
      clinical and laboratory criteria are available for the classification as systemic
      lupus erythematosus (SLE). The many different types of skin lesions encountered
      in patients with LE have been classified into those that are histologically
      specific for LE and those that are not. While LE non-specific skin lesions on
      their own do not enable a diagnosis of LE, they can be important reflections of
      underlying SLE disease activity. This also applies to the involvement of the
      scalp and nails. Finally, it must be kept in mind that LE patients may also
      develop drug-related, or other unrelated common disorders of the hair and nails
      that do not reflect LE disease activity.

PMID- 20693202
TI  - Diagnostic algorithm for Raynaud's phenomenon and vascular skin lesions in
      systemic lupus erythematosus.
AB  - Skin discolorations and skin lesions due to vascular pathologies are common
      clinical features in systemic lupus erythematosus. A variety of clinical
      manifestations such as Raynaud's phenomenon, acrocyanosis, livedo patterns,
      erythematous or violaceous macules and papules or necrosis are triggered by
      heterogeneous pathophysiological mechanisms such as vasospasm, vasculitis or
      thromboembolism. A standardized macro- and microvascular assessment is necessary
      to establish the correct diagnosis. We describe and illustrate common clinical
      features of vascular skin manifestations in systemic lupus erythematosus and
      present a diagnostic algorithm.

PMID- 20693203
TI  - Cutaneous manifestations of complement deficiencies.
AB  - In this review we address the main cutaneous manifestations and diseases
      associated with deficiencies in components of the complement system. The first
      part is devoted to hereditary angioedema, in which acute, sometimes life
      threatening recurrent attacks of acute swelling, usually associated with
      gastrointestinal symptoms, occur. It is related to a structural or functional
      deficiency of C1 esterase inhibitor. Patients usually have lowered C4 levels, and
      diagnosis relies on determination of antigenic and/or functional C1 inhibitor
      level. The second part focuses on lupus erythematosus, as deficiencies in early
      components of the complement system, such as C1q, C1r, C1s, C2 or C4, are the
      strongest known disease susceptibility genes for the development of human
      systemic lupus erythematosus. Severe infections early in life and marked
      photosensitivity in a patient with lupus erythematosus are clues to an underlying
      complement deficiency. The genetic background and the clinical associations of
      the different components of the complement system will be detailed.

PMID- 20693204
TI  - Drug-induced subacute cutaneous lupus erythematosus.
AB  - Subacute cutaneous lupus erythematosus (SCLE) is a subset of cutaneous lupus
      erythematosus with unique immunologic and clinical features. The first
      description dates back to 1985 when a series of five patients were found to have
      hydrochlorothiazide-induced SCLE. Since that time, at least 40 other drugs have
      been implicated in the induction of SCLE.

PMID- 20693205
TI  - Cutaneous lupus in infancy and childhood.
AB  - Cutaneous lupus may occur in infancy as transient lesions associated with and
      probably caused by maternal autoantibodies, or later in childhood, associated
      with the endogenous development of autoimmunity. In this review, clinical
      findings, diagnosis, management, and pathogenesis of neonatal lupus are
      discussed, and the management of cutaneous lupus in children is detailed.

PMID- 20693206
TI  - Epidemiologic, socioeconomic and psychosocial aspects in lupus erythematosus.
AB  - Epidemiologic, socioeconomic, and psychosocial factors play an important role in
      health care and handling of patients with the various clinical forms of lupus
      erythematosus (LE). Patients with LE are mostly young women; adolescents and some
      ethnic groups are especially prone to a severe course of disease. The
      unpredictable and fluctuating flares of disease, the need for longterm treatment,
      and the side effects and damage caused by the disease itself severely reduce
      quality of life. Problems arise, involving family members, adherence to medical
      advice and therapy, communication and self management. Socioeconomically,
      patients are often unable to take regular employment and to pay for health
      insurance. Stress factors that arise have a negative impact on the course of
      disease, increasing both fatigue and the basic burden of illness. Healthcare
      professionals must pay careful attention to all these items, as they attempt to
      treat flares, minimize drug side effects, provide pain relief, arrange
      communication and exercise programs along with behavioral and psychosocial
      interventions in multidisciplinary cooperation, and also involve and support
      family members.

PMID- 20693207
TI  - Treatment of cutaneous lupus erythematosus.
AB  - In patients with cutaneous lupus erythematosus (CLE) and mild skin involvement,
      local therapy consisting of topically applied pharmacological agents, e.g.,
      topical/intralesional steroids, may be sufficient. Recent reports have also shown
      efficacy of topical calcineurin inhibitors in patients with CLE, particularly on
      the face. Special attention receives consistent sun protection through
      photoresistant clothing and application of light-shielding substances with highly
      potent chemical or physical UVA- and UVB-protective filters. These substances
      should be applied in sufficient amount (ca. 2 mg/cm(2)) at least 20-30 minutes
      before sun exposure in order to avoid induction and exacerbation of cutaneous
      lesions. The mainstay of treatment for disfiguring and widespread skin
      manifestations in patients with CLE, irrespective of the subtype of the disease,
      is antimalarial agents. Our understanding of the use of combinations of
      antimalarials and proper dosing according to the ideal bodyweight limits problems
      with toxicity. Further therapies, such as methotrexate, or retinoids, dapsone,
      mycophenolate mofetil, and thalidomide in selected cases, can be helpful for
      patients with resistant disease; however, side effects need to be taken into
      consideration. Recent advances in biotechnology resulted in the development of
      novel systemic agents, but randomized controlled trials are necessary for the
      approval of new therapeutic strategies in CLE.

PMID- 20693209
TI  - The impact of the EUSCLE Core Set Questionnaire for the assessment of cutaneous
      lupus erythematosus.
AB  - Epidemiological data and standard European guidelines for the diagnosis and
      treatment of cutaneous lupus erythematosus (CLE) are lacking in the current
      literature. In order to provide a standardized tool for an extensive consistent
      data collection, a study group of the European Society of Cutaneous Lupus
      Erythematosus (EUSCLE) recently developed a Core Set Questionnaire for the
      assessment of patients with different subtypes of CLE. The EUSCLE Core Set
      Questionnaire includes six sections on patient data, diagnosis, skin involvement,
      activity and damage of disease, laboratory analysis, and treatment. An instrument
      like the EUSCLE Core Set Questionnaire is essential to gain a broad and
      comparable data collection of patients with CLE from different European centres
      and to achieve consensus concerning clinical standards for the disease. The data
      will also be important for further characterization of the different CLE subtypes
      and the evaluation of therapeutic strategies; moreover, the EUSCLE Core Set
      Questionnaire might also be useful for the comparison of data in clinical trials.
      In this review, the impact of the EUSCLE Core Set Questionnaire is discussed in
      detail with regard to clinical and serological features as well as therapeutic
      modalities in CLE.

PMID- 20693208
TI  - Clinical outcome measures for cutaneous lupus erythematosus.
AB  - Cutaneous lupus erythematosus (CLE) is a clinically heterogeneous group of rare
      skin diseases that only rarely have been subjected to controlled clinical trials.
      This may have been partly due to a lack of suitable validated outcome
      instruments. Recently, the Food and Drug Administration (FDA) mandated that organ
      specific trials for lupus erythematosus need to use a combination of different
      outcome measures. The patient's condition needs to be assessed in terms of
      quality of life, the patient's global response, and organ-specific instruments
      that measure activity of the disease as well as damage due to the disease. For
      the skin, the only formally validated and published instrument is currently the
      Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI). This paper
      discusses the background of the development of the CLASI as well as issues
      related to its use and interpretation in the context of clinical research of CLE.

PMID- 20693210
TI  - Dermatologist versus rheumatologist in the management of lupus patients: this
      debate between father (PF) and daughter (RF) is purely fictional, but it could
      have easily happened.

PMID- 20693211
TI  - WHO editorial. Technology for patient safety.

PMID- 20693212
TI  - Making existing technology safer in healthcare.
AB  - BACKGROUND: Technology, equipment and medical devices are vital for effective
      healthcare throughout the world but are associated with risks. These risks
      include device failure, inappropriate use, insufficient user-training and
      inadequate inspection and maintenance. Further risks within the developing world
      include challenging conditions of temperature and humidity, poor infrastructure,
      poorly trained service providers, limited resources and supervision, and
      inappropriately complex equipment being supplied without backup training for its
      use or maintenance. METHODS: This document is the product of an expert working
      group established by WHO Patient Safety to define the measures being taken to
      reduce these risks. It considers how the provision of safer technology services
      worldwide is being enhanced in three ways: through non-punitive and open
      reporting systems of technology-related adverse events and near-misses, with
      classification and investigation; through healthcare quality assessment,
      accreditation and certification; and by the investigation of how appropriate
      design and an understanding of the conditions of use and associated human factors
      can improve patient safety. RESULTS AND DISCUSSION: Many aspects of these steps
      remain aspirational for developing countries, where highly disparate needs and a
      vast range of technology-related problems exist. Here, much greater emphasis must
      be placed on failsafe, durable and user-friendly design--examples of which are
      described.

PMID- 20693213
TI  - Information technology for patient safety.
AB  - BACKGROUND: Research on patient care has identified substantial variations in the
      quality and safety of healthcare and the considerable risks of iatrogenic harm as
      significant issues. These failings contribute to the high rates of potentially
      avoidable morbidity and mortality and to the rising levels of healthcare
      expenditure seen in many health systems. There have been substantial developments
      in information technology in recent decades and there is now real potential to
      apply these technological developments to improve the provision of healthcare
      universally. Of particular international interest is the use of eHealth
      applications. There is, however, a large gap between the theoretical and
      empirically demonstrated benefits of eHealth applications. While these
      applications typically have the technical capability to help professionals in the
      delivery of healthcare, inadequate attention to the socio-technical dimensions of
      their use can result in new avoidable risks to patients. RESULTS AND DISCUSSION:
      Given the current lack of evidence on quality and safety improvements and on the
      cost-benefits associated with the introduction of eHealth applications, there
      should be a focus on implementing more mature technologies; it is also important
      that eHealth applications should be evaluated against a comprehensive and
      rigorous set of measures, ideally at all stages of their application life cycle.

PMID- 20693214
TI  - Technology as applied to patient safety: an overview.

PMID- 20693215
TI  - Training and simulation for patient safety.
AB  - BACKGROUND: Simulation-based medical education enables knowledge, skills and
      attitudes to be acquired for all healthcare professionals in a safe,
      educationally orientated and efficient manner. Procedure-based skills,
      communication, leadership and team working can be learnt, be measured and have
      the potential to be used as a mode of certification to become an independent
      practitioner. RESULTS: Simulation-based training initially began with life-like
      manikins and now encompasses an entire range of systems, from synthetic models
      through to high fidelity simulation suites. These models can also be used for
      training in new technologies, for the application of existing technologies to new
      environments and in prototype testing. The level of simulation must be
      appropriate to the learners' needs and can range from focused tuition to mass
      trauma scenarios. The development of simulation centres is a global phenomenon
      which should be encouraged, although the facilities should be used within
      appropriate curricula that are methodologically sound and cost-effective.
      DISCUSSION: A review of current techniques reveals that simulation can
      successfully promote the competencies of medical expert, communicator and
      collaborator. Further work is required to develop the exact role of simulation as
      a training mechanism for scholarly skills, professionalism, management and health
      advocacy.

PMID- 20693216
TI  - What should WHO be doing about patient safety and technology?

PMID- 20693217
TI  - Introducing new technology safely.
AB  - AIM: This report considers the introduction of new technology and the
      implications for patient safety. METHODS AND DISCUSSION: A distinction is made
      between 'conceptually' new and 'contextually' new technology. The life cycle of
      technology from development to routine use is discussed and the key role for
      regulation, health technology assessment, clinical engineering and surveillance
      in this life cycle considered. The limitations of each of these disciplines are
      also discussed. Special consideration is given to the needs of developing
      countries. Case study examples of particular challenges in the safe introduction
      of technology are presented.

PMID- 20693218
TI  - Place sustainability at the heart of the quality agenda.

PMID- 20693219
TI  - Progress in paediatric electronic prescribing: good, better, best.

PMID- 20693220
TI  - Evaluation ecology: a new perspective linking improvement and evaluation.

PMID- 20693221
TI  - Developing a common language for evaluation questions in quality and safety
      improvement.
AB  - Evaluation is an important component of service improvement but is not undertaken
      often enough. Many evaluation guides are available, and the language describing
      approaches is complex and varied. This variation is a potential barrier to
      evaluation, particularly in communication between practitioners. A structured
      literature review of development and evaluation frameworks for healthcare quality
      improvement was carried out. Four frameworks with diverse methodological
      perspectives were identified. Partial mapping was possible against an existing
      structure for health promotion research. When the questions in this framework
      were adapted for healthcare evaluation, it provided a common structure for the
      four frameworks. There is significant common ground underpinning these
      terminological differences between descriptions of evaluation techniques. The
      common language developed here has potential to ease communication in healthcare
      evaluation and improvements in quality and safety. It is an aid for practitioners
      in framing pragmatic evaluation of improvement projects.

PMID- 20693222
TI  - Paediatric dosing errors before and after electronic prescribing.
AB  - OBJECTIVE: To compare the incidence and severity rating of dose prescribing
      errors before and after the implementation of a commercially available electronic
      prescribing system at a tertiary care children's hospital. METHODS: Dose errors
      were identified using prescription review to detect errors. Severity rating was
      determined by five judges using a validated, reliable scoring tool. The mean
      score for each error was used as an index of severity. RESULTS: Dose prescribing
      errors occurred in 88 of the 3939 (2.2%) items prescribed for outpatients and
      inpatients, and on discharge prescriptions prior to the implementation of
      electronic prescribing (EP). After EP, there were 57 dose errors in 4784 (1.2%)
      items prescribed (1% absolute reduction (p<0.001 chi(2) test; 95% CI of
      difference in proportions -1.6% to -0.5%)). A decrease in the severity rating of
      dose errors was also seen: dose errors with potentially minor outcomes 35/3939
      (0.89%) pre vs 21/4784 (0.44%) post (95% CI of difference in proportions -0.8% to
      -0.11%, p=0.009 chi(2) test); moderate outcome 46/3939 (1.17%) pre vs 33/4784
      (0.69%) post (95% CI of difference in proportions -0.91% to -0.08, p=0.019,
      chi(2) test); severe outcome: 7/3939 (0.18%) pre vs 3/4784 (0.06%) post (95% CI
      of difference in proportions -0.31% to +0.04, p=0.11, chi(2) test). CONCLUSION:
      Electronic prescribing appears to reduce rates of dosing errors in paediatrics,
      but larger studies are required to assess the effect on the severity of these
      errors and in different settings.

PMID- 20693223
TI  - Improving safety culture on adult medical units through multidisciplinary
      teamwork and communication interventions: the TOPS Project.
AB  - AIM: The goal of this project was to improve unit-based safety culture through
      implementation of a multidisciplinary (pharmacy, nursing, medicine) teamwork and
      communication intervention. METHOD: The Agency for Healthcare Research and
      Quality Hospital Survey on Patient Safety Culture was used to determine the
      impact of the training with a before-after design. RESULTS: Surveys were returned
      from 454 healthcare staff before the training and 368 staff 1 year later. Five of
      eleven safety culture subscales showed significant improvement. Nurses perceived
      a stronger safety culture than physicians or pharmacists. CONCLUSION: While it is
      difficult to isolate the effects of the team training intervention from other
      events occurring during the year between training and postevaluation, overall the
      intervention seems to have improved the safety culture on these medical units.

PMID- 20693224
TI  - Menu selection, glycaemic control and satisfaction with standard and patient
      controlled consistent carbohydrate meal plans in hospitalised patients with
      diabetes.
AB  - PROBLEM: Medical nutrition therapy is an important component of glycaemic
      management in hospitalised patients with diabetes; however, there is a lack of
      information guiding the ordering of specific meal plans in this setting. SETTING:
      University-affiliated academic medical centre. METHODS: An administrative
      decision to gradually replace standard consistent-carbohydrate (CCMP) (standard
      group) with patient-controlled meal plans (patient-controlled group) presented
      the opportunity to compare menu selection, adherence to CCMP, glycaemic control
      and satisfaction as a quality-improvement initiative. Information was obtained
      from consecutive inpatients with diabetes admitted to units receiving standard
      (n=30) or patient-controlled meal plans (n=43). Patients received the meal plan
      according to unit location. RESULTS: No group differences were observed in
      adherence to CCMP (70% vs 64%, p=0.1), mean capillary blood glucose (CBG) or
      hyperglycaemia frequency (CBG>180 mg/dl). Hypoglycaemia (CBG<70 mg/dl) occurred
      more frequently in the patient-controlled group (0.39 vs 3.23%, p=0.04). There
      were no episodes of severe hypoglycaemia (CBG<40 mg/dl) in either group. The
      patient-controlled group reported a greater satisfaction and had more
      opportunities for nutrition education, with a demonstrated improvement in
      adherence to CCMP following targeted education in six of nine patients with
      available menu data. CONCLUSIONS: The standard group experienced less
      hypoglycaemia and required less clinician oversight. The patient-controlled group
      allowed for identification of patients who would benefit from education, required
      more oversight by nutrition services and reported greater satisfaction with their
      meal plan. Both meal plans may be appropriate for inpatients with diabetes,
      provided that a sufficient review is available for patients who make
      inappropriate selections with the patient-controlled meal plan.

PMID- 20693225
TI  - Medical team training and coaching in the Veterans Health Administration;
      assessment and impact on the first 32 facilities in the programme.
AB  - BACKGROUND: Communication is problematic in healthcare. The Veterans Health
      Administration is implementing Medical Team Training. The authors describe
      results of the first 32 of 130 sites to undergo the programme. This report is
      unique; it provides aggregate results of a crew resource-management programme for
      numerous facilities. METHODS: Facilities were taught medical team training and
      implemented briefings, debriefings and other projects. The authors coached teams
      through consultative phone interviews over a year. Implementation teams self
      reported implementation and rated programme impact: 1='no impact' and
      5='significant impact.' We used logistic regression to examine implementation of
      briefing/debriefing. RESULTS: Ninety-seven per cent of facilities implemented
      briefings and debriefings, and all implemented an additional project. As of the
      final interview, 73% of OR and 67% of ICU implementation teams self-reported and
      rated staff impact 4-5. Eighty-six per cent of OR and 82% of ICU implementation
      teams self-reported and rated patient impact 4-5. Improved teamwork was reported
      by 84% of OR and 75% of ICU implementation teams. Efficiency improvements were
      reported by 94% of OR implementation teams. Almost all facilities (97%) reported
      a success story or avoiding an undesirable event. Sites with lower volume were
      more likely to conduct briefings/debriefings in all cases for all surgical
      services (p=0.03). CONCLUSIONS: Sites are implementing the programme with a
      positive impact on patients and staff, and improving teamwork, efficiency and
      safety. A unique feature of the programme is that implementation was facilitated
      through follow-up support. This may have contributed to the early success of the
      programme.

PMID- 20693226
TI  - Priority setting in health care: Swedish efforts and experiences.

PMID- 20693229
TI  - Cardiovascular risk factors associated with migraine among the elderly with a low
      income: the Sao Paulo Ageing & Health Study (SPAH).
AB  - BACKGROUND: To investigate the association between cardiovascular risk-factor
      profile and migraine in the elderly, we evaluated a population sample of ageing
      men and women (65 years or more) living in a low-income area in the city of Sao
      Paulo, Brazil. PATIENTS AND METHODS: We investigated migraine status and
      cardiovascular profile from a baseline of 1450 participants (65-102 years of age)
      of the Sao Paulo Ageing & Health Study (SPAH), a longitudinal population-based
      study with low-income elderly in Brazil. The following age and sex-adjusted
      cardiovascular risk factors were analyzed: blood pressure, pulse pressure, serum
      total and high-density lipoprotein cholesterol, body mass index, smoking, history
      of hypertension, diabetes and the 10-year risk of myocardial infarction or
      coronary heart disease death based on the Framingham Risk Score. RESULTS: The
      overall prevalence of migraine was 11.4%, and it was 3 times more frequent among
      women than men (15.3% vs 5.4%; P < 0.0001). Migraineurs were younger than non
      migraineurs (mean age 70.6 years vs 72.1 years; P = 0.001, respectively). There
      was no statistically significant difference regarding the cardiovascular risk
      factor profile after adjustment for age and sex among migraineurs and non
      migraineurs. Only a decrease in the risk of hypertension among women (OR 0.58;
      95% CI 0.38-0.90; P = 0.01) was also observed even after adjustment for age.
      CONCLUSIONS: Overall, we did not find a worse cardiovascular risk profile among
      elderly migraineurs. An inverse association between hypertension and migraine in
      women warrants further investigation.

PMID- 20693230
TI  - Differential activation of the middle-temporal complex to visual stimulation in
      migraineurs.
AB  - OBJECTIVE: Differences between people with and without migraine on various
      measures of visual perception have been attributed to abnormal cortical
      processing due to the disease. The aim of the present study was to explore the
      dynamics of the basic interictal state with regard to the extrastriate, motion
      responsive middle temporal area (MT-complex) with functional magnetic resonance
      imaging (fMRI) at 3 tesla using coherent/incoherent moving dot stimuli. METHOD:
      Twenty-four migraine patients (12 with aura [MwA], 12 without aura [MwoA]) and 12
      healthy subjects participated in the study. The individual cortical folding
      pattern was accounted for by using a cortical matching approach. RESULTS: In the
      inferior-posterior portion of the MT-complex, most likely representing MT,
      control subjects showed stronger bilateral activation compared to MwA and MwoA
      patients. Compared with healthy controls MwoA and MwA patients showed
      significantly stronger activation mainly at the left side in response to visual
      stimulation in the superior-anterior portion of the MT-complex, representing the
      medial-superior temporal area (MST). CONCLUSION: Our findings strengthen the
      hypothesis that hyperresponsiveness of the visual cortex in migraine goes beyond
      early visual areas, even in the interictal period.

PMID- 20693231
TI  - Temporal profile of vascular changes induced by systemic nitroglycerin in the
      meningeal and cortical districts.
AB  - BACKGROUND: Clinical studies indicated that nitric oxide (NO) donors cause
      regional changes in cerebral blood flow (CBF), similar to those reported in
      spontaneous migraine. Systemic nitroglycerin (NTG), a NO donor, is a well
      accepted experimental model of migraine. In this study we have examined the
      effects of NTG on the meningeal and cortical blood flow in rats. METHODS:
      Regional blood flow was monitored in male Sprague-Dawley rats using laser Doppler
      flowmetry before and after NTG/saline injection over 150 minutes. The effect of
      pre-treatment with Nomega-nitro-L-arginine ester (L-NAME) or 7-nitroindazole (7
      NI) on NTG-induced changes on blood flow was also investigated. RESULTS: In the
      dura NTG caused a biphasic response represented by an initial decrease in blood
      flow followed by a significant increase. At variance, in the cortex NTG caused
      only an increase in blood flow. Pre-treatment with either L-NAME or 7-NI
      prevented NTG-induced increase in blood flow in both districts, while only L-NAME
      also prevented NTG-induced decrease in dural blood flow. CONCLUSION: The present
      findings provide additional information on the timing of effects of NTG on blood
      flow at both the meningeal and cortical levels. These effects seem to be related
      to vasoregulatory mechanisms and/or metabolic activity in response to the
      synthesis of endogenous NO.

PMID- 20693232
TI  - Production and characterization of monoclonal antibodies specific to
      lactotriaosylceramide.
AB  - We have established hybridoma cell lines producing monoclonal antibodies (mAbs)
      directed to N-acetylglucosaminylbeta1-3galactose (GlcNAcbeta1-3Gal) residue by
      immunizing BALB/c mice with lactotriaosylceramide (Lc(3)Cer). These obtained
      hybridoma cells, specific to Lc(3)Cer, were dual immunoglobulin (Ig)-producing
      cells which secreted both IgM and IgG molecules as antibodies. The established
      mAbs are able to react with not only Lc(3)Cer but also GlcNAcbeta1-3-terminal
      glycosphingolipids (GSLs) despite branching or lactosamine chain lengths and
      human transferrin with terminal GlcNAc residues. Comparison of the variable
      regions of the cloned IgM and IgG by reversed transcription-polymerase chain
      reaction analysis confirmed that the variable regions determine the specificity,
      the other amino acids are conserved, and these mAbs are encoded by J558 and
      Vkappa-21family genes. Furthermore, we have analyzed the expression of GSLs with
      GlcNAcbeta1-3 epitope in acute leukemia cell lines and mouse fetal tissues using
      these mAbs, in which antigens were distributed comparatively. These mAbs are
      useful for studying the precise distribution of GlcNAcbeta1-3Gal-terminating GSL
      expression in tissues as well as for detecting GSLs carrying terminal GlcNAcbeta1
      3Gal carbohydrate structure.

PMID- 20693233
TI  - Tobacco smoking in urban neighborhoods: exploring social capital as a protective
      factor in Santiago, Chile.
AB  - INTRODUCTION: Research examining the relationship between social capital and
      health in Latin America has been limited. The aim of this study is to evaluate
      the association between social capital and tobacco use in four low-income
      neighborhoods in Santiago, Chile. METHODS: A multistage probability sample was
      used to select households in 4 of the 10 poorest neighborhoods in the district of
      Puente Alto, in Santiago, Chile. A cross-sectional survey of 781 participants
      (81.2% response rate for households) included sociodemographic variables,
      questions pertaining to neighborhood social capital, and questions pertaining to
      tobacco. Main analyses were carried out at the individual level by performing a
      multiple logistic regression of individual tobacco use on individual perceptions
      of community social capital. RESULTS: The prevalence of smoking was 43.9% of the
      surveyed population. A five-factor structure for social capital was identified,
      including "perceived trust in neighbors," "perceived trust in organizations,"
      "reciprocity within the neighborhood," "neighborhood integration," and "social
      participation." An inverse relationship between trust in neighbors and tobacco
      smoking was statistically significantly with an adjusted odds ratio of 0.95 (95%
      CI: 0.91-0.99). Trust in neighbors was also significantly inversely associated
      with the number of cigarettes smoked. DISCUSSION: Tobacco control remains a
      significant challenge in global health, requiring innovative strategies that
      address changing social contexts as well as the changing epidemiological profile
      of developing regions.

PMID- 20693236
TI  - Survey of injecting drug users' health shows mixed picture.

PMID- 20693237
TI  - Longitudinal changes in access to health care by immigrant status among older
      adults: the importance of health insurance as a mediator.
AB  - PURPOSE: This longitudinal study examined the role of health insurance in access
      to health care among older immigrants. DESIGN AND METHODS: Using data from the
      Second Longitudinal Study of Aging, the longitudinal trajectories of having a
      usual source of care were compared between 3 groups (all 70+ years): (a) late
      life immigrants with less than 15 years of residence in the United States
      ("recent immigrants"; n = 133), (b) "earlier immigrants" (15 years or longer in
      the United States, n = 672), and (c) U.S. born (n = 8,642). A series of
      hierarchical generalized linear models were run to test the mediating
      relationship of health insurance between immigrant status and having a usual
      source of care. RESULTS: Although the probabilities of having a usual source of
      care increased over time across all three groups, recent immigrants were less
      likely to have Medicare and private insurance over time; this in turn was related
      to lower probabilities of having a usual source of care (indirect relationship).
      There was no direct relationship between immigrant status and having a usual
      source of care. IMPLICATIONS: To prevent the use of more expensive forms of care
      in the long run, policy efforts should expand late-life immigrants' health
      insurance coverage by increasing affordable health insurance options.

PMID- 20693238
TI  - A systematic review assessing the effectiveness of interventions to improve
      persistence with anti-resorptive therapy in women at high risk of clinical
      fracture.
AB  - BACKGROUND: despite availability of effective treatments for osteoporosis, impact
      on fracture rates may be suboptimal because of failure to adhere to recommended
      anti-resorptive therapy. OBJECTIVE: to identify randomized controlled trials
      (RCTs) evaluating interventions intended to improve persistence with anti
      resorptive therapy for treating women with osteoporosis or osteopenia. The design
      of the study is a systematic review and meta-analysis of RCTs. METHODS: included
      trials were those reporting interventions to improve persistence with or
      adherence to anti-resorptive treatment compared to a control medication or usual
      care. A search of MEDLINE, EMBASE, CINAHL and the Cochrane Library was
      supplemented by review of cited literature. Reports were reviewed and data pooled
      where appropriate. The primary outcome was duration of persistence with
      medication. RESULTS: six trials met inclusion criteria, including four reporting
      persistence as an outcome measure indicating a relative reduction in non
      persistence of 22% (pooled relative risk: 0.78, 95% confidence interval 0.65
      0.95) for active compared to control interventions. Heterogeneity between the
      trial effects was present but not significant (I(2) = 47%, P = 0.11).
      Interventions were varied in design, and some measurements of adherence were
      subject to self-report bias. Two trials included the majority of participants
      (3386/3497), accounting for >90% of the weight in the pooled estimate.
      CONCLUSIONS: trials to date suggest potential for improving persistence with
      medication taking thus improving treatment outcomes and reducing fracture risk.
      More precise measurement of medication taking and promoting fidelity to a
      precisely defined intervention protocol may lead to better assessment of impact
      on clinically important outcomes.

PMID- 20693239
TI  - Size and spatial orientation of uterine tissue transplants on the peritoneum
      crucially determine the growth and cyst formation of endometriosis-like lesions
      in mice.
AB  - BACKGROUND: In many studies in rodents, intraperitoneal endometriosis-like
      lesions are surgically induced by syngeneic or autologous transplantation of
      uterine tissue samples, which are sutured to the abdominal wall. However, until
      now the surgical techniques have not been standardized, and we address this issue
      here. METHODS: Uterine tissue samples were transplanted to the peritoneum of
      C57BL/6 mice (four study groups, n = 7 each). Using non-invasive high-resolution
      ultrasound imaging over a period of 4 weeks, we analyzed growth characteristics
      and cyst formation of the endometriosis-like lesions which developed, in relation
      to mode of transplantation (syngeneic versus autologous), type of tissue fixed
      adjacent to the peritoneum (endometrium versus perimetrium), and size of tissue
      transplanted (2 versus 3 mm). Immunohistochemical analysis was also performed.
      RESULTS: When the perimetrium, with underlying myometrium, was sutured next to
      the host peritoneum the endometriosis-like lesions which developed exhibited a
      higher growth rate (P< 0.05 versus endometrium), and contained more proliferating
      cell nuclear antigen (PCNA)-positive cells and an increased microvessel density
      (both P< 0.05 versus endometrium). In the group with 3 mm uterine tissue grafts,
      lesion growth was significantly decreased when compared with 2 mm samples (P<
      0.05). However, the larger grafts developed more cysts throughout the observation
      period than the smaller ones. There was no difference between syngeneic and
      autologous endometriosis-like lesions. CONCLUSIONS: Our study demonstrates that
      size and spatial orientation of peritoneally fixed uterine tissue samples
      crucially determine growth and cyst formation of endometriotic lesions in mice.
      These findings should improve the standardization and reliability of future
      studies, performed in the frequently used mouse model of surgically induced
      endometriosis.

PMID- 20693240
TI  - The R438W polymorphism of human DNA polymerase lambda triggers cellular
      sensitivity to camptothecin by compromising the homologous recombination repair
      pathway.
AB  - The human DNA polymerase lambda (Pollambda) is a DNA repair polymerase, which is
      believed not only to play a role in base excision repair but also to contribute
      to DNA double-strand break repair by non-homologous end joining. We described
      here that cellular expression of the recently described natural polymorphic
      variant of Pollambda, Pollambda(R438W), affects the homologous recombination (HR)
      pathway and sister chromatid exchange (SCE) events. We show that the HR defect
      provoked by this polymorphism enhances cellular sensitivity to the anticancer
      agent camptothecin (CPT), most of whose DNA damage is repaired by HR. All these
      effects were dependent on the DNA polymerase activity of Pollambda(R438W) as the
      expression of a catalytically inactive Pollambda(R438W) did not affect either the
      HR and SCE frequencies or the cellular sensitivity to CPT. These results suggest
      that sensitivity to CPT could result from cancer-related mutation in specialized
      DNA repair polymerases.

PMID- 20693241
TI  - Widespread losses of vomeronasal signal transduction in bats.
AB  - The vertebrate vomeronasal system (VNS) detects intraspecific pheromones and
      environmental odorants. We sequenced segments of the gene encoding Trpc2, an ion
      channel crucial for vomeronasal signal transduction, in 11 species that represent
      all main basal lineages of Yinpterochiroptera, one of the two suborders of the
      order Chiroptera (bats). Our sequences show that Trpc2 is a pseudogene in each of
      the 11 bats, suggesting that all yinpterochiropterans lack vomeronasal
      sensitivity. The Trpc2 sequences from four species of Yangochiroptera, the other
      suborder of bats, suggest vomeronasal insensitivity in some but not all
      yangochiropterans. These results, together with the available morphological data
      from the bat VNS, strongly suggest multiple and widespread losses of vomeronasal
      signal transduction and sensitivity in bats. Future scrutiny of the specific
      functions of the VNS in the few bats that still retain the VNS may help explain
      why it is dispensable in most bats.

PMID- 20693242
TI  - Interstitial pressure and lung oedema in chronic hypoxia.
AB  - We evaluated how the increase in lung interstitial pressure correlates with the
      pulmonary vascular response to chronic hypoxia. In control and hypoxic (30 days;
      10% O2) Wistar male rats, we measured: pulmonary interstitial pressure (P(ip)),
      cardiac and haemodynamic parameters by echocardiography, and performed lung
      morphometry on tissue specimens fixed in situ. In control animals, mean +/- sd
      P(ip), air/tissue volume ratio and capillary vascularity index in the air-blood
      barrier were -12 +/- 2.03 cmH2O, 3.9 and 0.43, respectively. After hypoxia
      exposure, the corresponding values of these indices in apparently normal lung
      regions were 2.6 +/- 1.7 cmH2O, 3.6, and 0.5, respectively. In oedematous
      regions, the corresponding values were 12 +/- 4 cmH2O, 0.4 and 0.3, respectively.
      Furthermore, in normal regions, the density of pre-capillary vessels (diameter
      ~50-200 MUm) increased and their thickness/internal diameter ratio decreased,
      while opposite results were found in oedematous regions. Pulmonary artery
      pressure increased in chronic hypoxia relative to the control (39.8 +/- 5.9
      versus 26.2 +/- 2.2 mmHg). Heterogeneity in local lung vascular response
      contributes to developing pulmonary hypertension in chronic hypoxia. In
      oedematous regions, the decrease in capillary vascularity correlated with the
      remarkable increase in interstitial pressure and morphometry of the pre-capillary
      vessels suggested an increase in vascular resistance; the opposite was true in
      apparently normal regions.

PMID- 20693243
TI  - Once-daily indacaterol versus twice-daily salmeterol for COPD: a placebo
      controlled comparison.
AB  - Indacaterol is a novel, inhaled, once-daily, ultra-long-acting beta(2)-agonist
      bronchodilator recently approved in Europe for the treatment of chronic
      obstructive pulmonary disease (COPD). The aim of the present study was to
      investigate the efficacy and safety of indacaterol compared with placebo and the
      twice-daily beta(2)-agonist, salmeterol, as an active control. Patients with
      moderate-to-severe COPD were randomised to 6 months double-blind treatment with
      indacaterol (150 MUg once daily), salmeterol (50 MUg twice daily) or placebo. The
      primary efficacy end-point was trough (24 h post-dose) forced expiratory volume
      in 1 s (FEV(1)) after 12 weeks. 1,002 patients were randomised and 838 (84%)
      completed the study. Indacaterol increased trough FEV(1) at week 12 by 170 mL
      over placebo (p<0.001) and by 60 mL over salmeterol (p<0.001). Both active
      treatments improved health status (St George's Respiratory Questionnaire) and
      dyspnoea (transition dyspnoea index) compared with placebo, with differences
      between them favouring indacaterol. Safety profiles were similar across the
      treatment groups, and both indacaterol and salmeterol were well tolerated. Once
      daily treatment with 150 MUg indacaterol had a significant and clinically
      relevant bronchodilator effect over 24 h post-dose and improved health status and
      dyspnoea to a greater extent than twice-daily 50 MUg salmeterol. Indacaterol
      should prove a useful additional treatment for patients with COPD.

PMID- 20693244
TI  - Association between human rhinovirus C and severity of acute asthma in children.
AB  - A new and potentially more pathogenic group of human rhinovirus (HRV), group C
      (HRVC), has recently been discovered. We hypothesised that HRVC would be present
      in children with acute asthma and cause more severe attacks than other viruses or
      HRV groups. Children with acute asthma (n = 128; age 2-16 yrs) were recruited on
      presentation to an emergency department. Asthma exacerbation severity was
      assessed, and respiratory viruses and HRV strains were identified in a nasal
      aspirate. The majority of the children studied had moderate-to-severe asthma
      (85.2%) and 98.9% were admitted to hospital. HRV was detected in 87.5% and other
      respiratory viruses in 14.8% of children, most of whom also had HRV. HRVC was
      present in the majority of children with acute asthma (59.4%) and associated with
      more severe asthma. Children with HRVC (n = 76) had higher asthma severity scores
      than children whose HRV infection was HRVA or HRVB only (n = 34; p = 0.018), and
      all other children (n = 50; p = 0.016). Of the 19 children with a non-HRV virus,
      13 had HRV co-infections, seven of these being HRVC. HRVC accounts for the
      majority of asthma attacks in children presenting to hospital and causes more
      severe attacks than previously known HRV groups and other viruses.

PMID- 20693245
TI  - A comparative study of two- versus one-lung ventilation for needlescopic bleb
      resection.
AB  - This prospective study was conducted to evaluate the feasibility of two-lung (TL)
      ventilation with low tidal volume anaesthesia compared with one-lung (OL)
      ventilation for needlescopic bleb resection. Patients with spontaneous
      pneumothorax that underwent bleb resection with a 2-mm thoracoscope were
      enrolled. During the operation, the tidal volume was set at 4.0 mL.kg-1 in the TL
      group and 8.0 mL.kg-1 in the OL group; the respiration rate was set at 23 and 12
      breaths.min-1, respectively, at the same inspiratory oxygen fraction (50%). A
      total of 108 patients (55 patients in the TL group and 53 in the OL group) were
      included in this study. Airway pressure was significantly lower in the TL group
      (mean +/- sd 8.0 +/- 3.3 versus 24.0 +/- 3.9 mmHg in the OL group; p<0.001). The
      time from endotracheal intubation to the incision was 17.1 +/- 4.0 min in the TL
      group and 35.3 +/- 7.6 min in the OL group, which was significantly different
      (p<0.001). However, the operation time was not different in comparisons between
      the two groups. Therefore, the total anaesthesia time was significantly longer in
      the OL group (77.9 +/- 21.6 versus 64.9 +/- 14.7 min in the TL group; p = 0.002).
      Needlescopic bleb resection using TL ventilation anaesthesia with low tidal
      volume was technically feasible, cost-effective and time-saving compared with OL
      ventilation anaesthesia.

PMID- 20693246
TI  - Inhibition of p38 MAPK-dependent bronchial contraction after ozone by
      corticosteroids.
AB  - We determined the role of p38 mitogen-activated protein kinase (MAPK) in the
      increased airway smooth muscle (ASM) contractile responses following ozone and
      modulation by corticosteroids. Mice were exposed to air or ozone (3 ppm for 3 h)
      and isometric contractile responses of bronchial rings to acetylcholine (ACh)
      were measured using a myograph in the presence of p38 MAPK inhibitor, SB239063
      (10-6 M) or dexamethasone (10-6 M). Because MAPK phosphatase (MKP)-1 is a
      negative regulator of p38 MAPK, we also studied these effects in MKP-1(-/-) mice.
      Bronchial rings from ozone-exposed wild-type and MKP-1(-/-) mice showed increased
      contractile responses, with a leftward shift of the dose-response curve in MKP-1(
      /-) mice. SB239063 inhibited bronchial contraction equally in air- and ozone
      exposed C57/BL6 and MKP-1(-/-) mice. Dexamethasone inhibited ACh-induced
      bronchial contraction in both air- and ozone-exposed C57/BL6 mice, but not in air
      or ozone-exposed MKP-1(-/-) mice. ACh-stimulated p38 MAPK and heat shock protein
      (HSP)27 phosphorylation, as measured by Western blotting, and this effect was
      suppressed by SB239063 in C57/BL6 and MKP-1(-/-) mice, but not by dexamethasone
      in either air- or ozone-exposed MKP-1(-/-) mice. p38 MAPK plays a role in maximal
      ACh-induced isometric contractile responses and increased contractility induced
      by ozone. Dexamethasone inhibits ACh-induced ASM contraction through
      phosphorylation of p38 MAPK and HSP27.

PMID- 20693248
TI  - The effect of dornase alfa on ventilation inhomogeneity in patients with cystic
      fibrosis.
AB  - Outcome measures to assess therapeutic interventions in cystic fibrosis (CF)
      patients with mild lung disease are lacking. Our aim was to determine if the lung
      clearance index (LCI) can detect a treatment response to dornase alfa in
      paediatric CF patients with normal spirometry. CF patients between 6-18 yrs of
      age with FEV(1 )>= 80% pred were eligible. In a crossover design, 17 patients
      received 4 weeks of dornase alfa and placebo in a randomised sequence separated
      by a 4-week washout period. The primary end-point was the change in LCI from
      dornase alfa versus placebo. A mixed model approach incorporating period
      dependent baselines was used. The mean +/- sd age was 10.32 +/- 3.35 yrs. Dornase
      alfa improved LCI versus placebo (0.90 +/- 1.44; p = 0.022). Forced expiratory
      flow at 25-75% expired volume measured by % pred and z-scores also improved in
      subjects on dornase alfa (6.1% +/- 10.34%; p = 0.03 and 0.28 +/- 0.46 z-score; p
      = 0.03). Dornase alfa significantly improved LCI. Therefore the LCI may be a
      suitable tool to assess early intervention strategies in this patient population.

PMID- 20693249
TI  - A noninvasive algorithm to exclude pre-capillary pulmonary hypertension.
AB  - Current guidelines recommend right heart catheterisation (RHC) in symptomatic
      patients at risk of pre-capillary pulmonary hypertension (PH) with
      echocardiographic systolic pulmonary artery pressures >= 36 mmHg. Growing
      awareness for PH, a high prevalence of post-capillary PH and the inability to
      distinguish between pre- and post-capillary PH by echocardiography have led to
      unnecessary RHCs. The aim of our study was to assess whether standard noninvasive
      diagnostic procedures are able to safely exclude pre-capillary PH. Data from 251
      patients referred for suspicion of pre-capillary PH were used to develop a
      noninvasive diagnostic decision tree. A prospectively collected data set of 121
      consecutive patients was utilised for temporal validation. According to the
      decision tree, patients were stratified by the presence or absence of an
      electrocardiographic right ventricular strain pattern (RVS) and serum N-terminal
      brain natriuretic peptide (NT-proBNP) levels below and above 80 pg.mL-1. In the
      absence of RVS and elevated NT-proBNP, none of the patients in the prospective
      validation cohort were diagnosed with pre-capillary PH by RHC. Combining
      echocardiography with the diagnostic algorithm increased specificity to 19.3% (p
      = 0.0009), while sensitivity remained at 100%. Employing ECG and NT-proBNP on top
      of echocardiography helps recognise one false positive case per five patients
      referred with dyspnoea and echocardiographic suspicion of PH, while not missing
      true pre-capillary PH.

PMID- 20693250
TI  - Bone marrow-derived mononuclear cell therapy attenuates silica-induced lung
      fibrosis.
AB  - This study tests the hypothesis that bone marrow-derived mononuclear cell (BMDMC)
      therapy may reduce lung inflammation and fibrosis leading to an improvement in
      respiratory mechanics in a murine model of silicosis. 52 female C57BL/6 mice were
      randomly assigned into four groups. In the silica group (SIL), silica suspension
      (20 mg/50 MUL in saline) was intratracheally instilled. In the control animals,
      50 MUL saline was administered intratracheally. At 1 h, the control and SIL
      groups were further randomised, receiving BMDMC (2*106 i.v. control-cell and SIL
      cell) or saline (50 MUL i.v. control and SIL). BMDMC were obtained from male
      donor mice. At day 15, lung mechanics, histology, and the presence of Y
      chromosome, interleukin (IL)-1beta, IL-1alpha, IL-1 receptor antagonist (IL-1RN),
      IL-1 receptor type 1, transforming growth factor (TGF)-beta and caspase-3 mRNA
      expressions in lung tissue were analysed. In the SIL-cell group, the fraction
      area of granuloma, the number of macrophages and the collagen fibre content were
      reduced, yielding improved lung mechanics. The presence of male donor cells in
      lung tissue was not confirmed using detection of Y chromosome DNA. Nevertheless,
      caspase-3, IL-1beta, IL-1alpha, IL-1RN and TGF-beta mRNA expression diminished
      after cell therapy. In conclusion, BMDMC acted on inflammatory and fibrogenic
      processes improving lung function through paracrine effects.

PMID- 20693251
TI  - Pulmonary hypertension in smoking mice over-expressing protease-activated
      receptor-2.
AB  - The mechanism(s) involved in the development of pulmonary hypertension (PH) in
      COPD is still the object of investigation. Cigarette smoke (CS) may lead to
      remodelling of intrapulmonary vessels and dynamic changes in vascular function,
      at least in some smokers. A role for proteases in PH has been recently put
      forward. We investigated, in smoking mice, the role of protease-activated
      receptor (PAR)-2 in the pathogenesis of PH associated with emphysema. We
      demonstrated that CS exposure can modulate PAR-2 expression in mouse lung. Acute
      CS exposure induces in wildtype (WT) and in transgenic mice over-expressing PAR-2
      (FVB(PAR-2-TgN)) a similar degree of neutrophil influx in bronchoalveolar lavage
      fluids. After chronic CS exposure WT and FVB(PAR-2-TgN) mice show emphysema, but
      only transgenic mice develop muscularisation of small intrapulmonary vessels that
      precedes the development of PH (~45% increase) and right ventricular hypertrophy.
      Smoking in FVB(PAR-2-TgN) mice results in an imbalance between vasoconstrictors
      (especially endothelin-1) and vasodilators (i.e. vascular endothelial growth
      factor, endothelial nitric oxide synthase and inducible nitric oxide synthase)
      and enhanced production of growth factors involved both in fibroblast-smooth
      muscle cell transaction (i.e. platelet-derived growth factor (PDGF) and
      transforming growth factor beta) and vascular cell proliferation (PDGF). PAR-2
      signalling can influence the production and release of many factors, which may
      play a role in the development of PH in smokers.

PMID- 20693252
TI  - Improving standards in flexible bronchoscopy for lung cancer.
AB  - Can the detection rate of flexible bronchoscopy for lung cancer be increased by a
      series of simple quality improvement measures? Bronchoscopy-associated clinical
      parameters were prospectively recorded between 2001 and 2007 in patients with
      suspected lung malignancy. The detection rate of bronchoscopy, diagnostic yield
      of each biopsy modality and the possible impact of different service-improvement
      measures were assessed. 746 bronchoscopies were performed in 704 patients. The
      detection rate of bronchoscopy for malignancy was 83.6%, and increased over time
      (67.3% detection rate in 2001 (95% CI 52.9-79.7), 89.7% detection rate in 2007
      (95% CI 81.3-95.2); p<0.001). Detection rate increased for bronchoscopically
      visible (75.0% in 2001 to 94.5% in 2007) and non-visible tumours (41.7% in 2001
      to 81.2% in 2007; p<0.001 for both analyses). Prior computed tomography
      availability was associated with a higher diagnostic yield that did not reach
      statistical significance. Logistic regression analysis identified tumour
      visibility, year of study, use of transbronchial needle aspiration and
      pathologist identity as independent predictors of a positive diagnosis. A
      significant increase in bronchoscopic detection rate for malignancy occurred in
      association with a number of simple improvement measures.

PMID- 20693253
TI  - Radial probe endobronchial ultrasound for the diagnosis of peripheral lung
      cancer: systematic review and meta-analysis.
AB  - Improved diagnostic sensitivity of bronchsocopy for the investigation of
      peripheral pulmonary lesions (PPLs) with the use of radial probe endobroncial
      ultrasound (EBUS) has been reported, although diagnostic performance varies
      considerably. A systematic review of published literature evaluating radial probe
      EBUS accuracy was performed to determine point sensitivity and specificity, and
      to construct a summary receiver-operating characteristic curve. Sub-group
      analysis and linear regression was used to identify possible sources of study
      heterogeneity. 16 studies with 1,420 patients fulfilled inclusion criteria.
      Significant inter-study variation in EBUS method was noted. EBUS had point
      specificity of 1.00 (95% CI 0.99-1.00) and point sensitivity of 0.73 (95% CI 0.70
      0.76) for the detection of lung cancer, with a positive likelihood ratio of 26.84
      (12.60-57.20) and a negative likelihood ratio of 0.28 (0.23-0.36). Significant
      inter-study heterogeneity for sensitivity was observed, with prevalence of
      malignancy, lesion size and reference standard used being possible sources. EBUS
      is a safe and relatively accurate tool in the investigation of PPLs. Diagnostic
      sensitivity of EBUS may be influenced by the prevalence of malignancy in the
      patient cohort being examined and lesion size. Further methodologically rigorous
      studies on well-defined patient populations are required to evaluate the
      generalisability of our results.

PMID- 20693254
TI  - Hypersensitivity pneumonitis and metalworking fluids contaminated by
      mycobacteria.
AB  - Metalworking fluids (MWF) are responsible for hypersensitivity pneumonitis (HP).
      The aim of the present study was to identify the antigen (Ag) responsible for MWF
      associated HP, and to optimise serological diagnosis by definition of a threshold
      allowing discrimination between HP patients and asymptomatic exposed workers. 13
      patients, who were workers at a car engine manufacturing plant, were suspected of
      MWF-associated HP. Microbial analysis of 83 used MWFs was carried out. Sera from
      13 MWF-associated HP patients, 12 asymptomatic exposed workers and 18 healthy
      unexposed controls were tested to determine their immunological responses to
      three Ags, including Mycobacterium immunogenum. M. immunogenum was identified in
      40% of used fluids by culture and confirmed by DNA sequencing. The threshold for
      differentiating MWF-associated HP patients from asymptomatic exposed workers was
      five arcs of precipitation (sensitivity 77% and specificity 92%), as determined
      by electrosyneresis (ES). Using ELISA methods with protein extract from M.
      immunogenum, a threshold leading to 92% sensitivity and 100% specificity was
      established. The detection of specific antibodies against M. immunogenum Ag at
      high levels in case sera suggests that M. immunogenum-contaminated MWF is
      responsible for MWF-associated HP. To discriminate MWF-associated HP patients
      from asymptomatic exposed workers, we suggest a five-arc threshold for ES and a
      1.6-AU threshold for ELISA methods.

PMID- 20693255
TI  - Dexamethasone reverses monocrotaline-induced pulmonary arterial hypertension in
      rats.
AB  - Pulmonary arterial hypertension (PAH) is associated with dysregulated bone
      morphogenetic protein receptor (BMPR)-II signaling and pulmonary vascular
      inflammation. We evaluated the effects of dexamethasone on monocrotaline (MCT)
      induced PAH in rats for potential reversal of PAH at late time-points. Saline
      treated control, MCT-exposed, MCT-exposed and dexamethasone-treated rats (5 mg.kg
      1.day-1, 1.25 mg.kg-1 and 2.5 mg.kg-1.48 h-1) were evaluated at day 28 and day 35
      following MCT for haemodynamic parameters, right ventricular hypertrophy,
      morphometry, immunohistochemistry, and IL6 and BMPR2 expression. Dexamethasone
      improved haemodynamics and pulmonary vascular remodelling, preventing PAH
      development at early (day 1-14 and 1-28) and reversing PAH at late (day 14-28 and
      21-35) time-points following MCT, as well as improving survival in MCT-exposed
      rats compared with controls. Both MCT-induced pulmonary IL6 overexpression and
      interleukin (IL)-6-expressing adventitial inflammatory cell infiltration were
      reduced with dexamethasone. This was associated with pulmonary BMPR2
      downregulation following MCT, which was increased with dexamethasone, in whole
      lung and control pulmonary artery smooth muscle cells. Dexamethasone also reduced
      proliferation of rat pulmonary artery smooth muscle cells in vitro. Experimental
      PAH can be prevented and reversed by dexamethasone, and survival is improved. In
      this model, mechanisms may involve reduction of IL-6-expressing inflammatory
      cells, restoration of pulmonary BMPR2 expression and reduced proliferation of
      vascular smooth muscle cells.

PMID- 20693247
TI  - The minimal important difference of exercise tests in severe COPD.
AB  - Our aim was to determine the minimal important difference (MID) for 6-min walk
      distance (6MWD) and maximal cycle exercise capacity (MCEC) in patients with
      severe chronic obstructive pulmonary disease (COPD). 1,218 patients enrolled in
      the National Emphysema Treatment Trial completed exercise tests before and after
      4-6 weeks of pre-trial rehabilitation, and 6 months after randomisation to
      surgery or medical care. The St George's Respiratory Questionnaire (domain and
      total scores) and University of California San Diego Shortness of Breath
      Questionnaire (total score) served as anchors for anchor-based MID estimates. In
      order to calculate distribution-based estimates, we used the standard error of
      measurement, Cohen's effect size and the empirical rule effect size. Anchor-based
      estimates for the 6MWD were 18.9 m (95% CI 18.1-20.1 m), 24.2 m (95% CI 23.4-25.4
      m), 24.6 m (95% CI 23.4-25.7 m) and 26.4 m (95% CI 25.4-27.4 m), which were
      similar to distribution-based MID estimates of 25.7, 26.8 and 30.6 m. For MCEC,
      anchor-based estimates for the MID were 2.2 W (95% CI 2.0-2.4 W), 3.2 W (95% CI
      3.0-3.4 W), 3.2 W (95% CI 3.0-3.4 W) and 3.3 W (95% CI 3.0-3.5 W), while
      distribution-based estimates were 5.3 and 5.5 W. We suggest a MID of 26 +/- 2 m
      for 6MWD and 4 +/- 1 W for MCEC for patients with severe COPD.

PMID- 20693256
TI  - Surfactant protein B polymorphisms, pulmonary function and COPD in 10,231
      individuals.
AB  - The surfactant protein (SP)-B gene may influence chronic obstructive pulmonary
      disease (COPD) and, thus, personalised medicine. We tested whether functional
      polymorphisms in SP-B (rs1130866 (1580T>C), rs2077079 (-18A>C) and rs3024791 (
      384G>A)) associate with reduced lung function and risk of COPD in the general
      population. We genotyped 10,231 individuals from the general adult Danish
      population, and recorded spirometry and hospital admissions due to COPD. Because
      we previously found an association between the rare SP-B 121ins2 mutation and
      COPD among smokers, we stratified the analyses for smoking status. None of the
      individual SP-B genotypes or genotype combinations were associated with reduced
      forced expiratory volume in 1 s (FEV1) % predicted, forced vital capacity (FVC) %
      pred and FEV1/FVC overall or among smokers (p = 0.25-0.99). The odds ratio for
      spirometrically defined COPD did not differ from 1.0 for any of the SP-B
      genotypes or genotype combinations overall or among smokers (p = 0.17-0.78).
      Similar results were obtained for hospitalisation due to COPD (p = 0.07-0.93); we
      could exclude overall hazard ratios for heterozygotes of 1.18-1.21 and for
      homozygotes of 1.25-1.57 or larger for all three polymorphisms. In conclusion,
      the functional rs1130866, rs2077079 and rs3024791 polymorphisms in the SP-B gene
      are not associated with reduced lung function or risk of COPD, making it unlikely
      that these variants will be useful in personalised medicine.

PMID- 20693257
TI  - Treatment of latent infection with Mycobacterium tuberculosis: update 2010.
AB  - Much remains unknown about latent infection with Mycobacterium tuberculosis.
      Existing immunodiagnostic tools for this condition have various limitations, most
      importantly in their ability to predict disease. Randomised controlled trials
      have established protective efficacy of isoniazid therapy for 6-12 months among
      non-HIV-infected and HIV-infected subjects. While efficacy may reach 90%,
      acceptance and adherence to prolonged therapy are less than desired. Rifampicin
      plus pyrazinamide for 2 months, though efficacious, has been associated with
      excess hepatotoxicity in non-HIV-infected persons. Isoniazid plus rifampicin for
      3 months has proven efficacy, but adverse effects may be more frequent than
      isoniazid or rifampicin monotherapy. Rifampicin monotherapy for 3-4 months is
      well tolerated, but efficacy data are currently limited, and concerns remain over
      possible selection of rifampicin-resistant mutants. For contacts of patients with
      multidrug-resistant tuberculosis, expert opinions differ on whether to treat with
      at least two drugs or just a fluoroquinolone, and for how long. With the existing
      diagnostic and treatment tools, efficacy of preventive therapy does not
      necessarily translate into field effectiveness. A targeted approach is required
      to maximise cost-effectiveness. Each geographic region needs to set its own
      priority after taking into account available scientific data and local
      circumstances.

PMID- 20693258
TI  - No increase in the prevalence of COPD in two decades.
AB  - Relevant information on the prevalence of chronic obstructive pulmonary disease
      (COPD) and its trends is scarce. In the present study, we compare the prevalence
      rates and potential determinants of COPD in two national population samples that
      were surveyed 20 yrs apart. In 1978-1980, a sample of 8,000 people was surveyed;
      subjects were representative of the Finnish population and were aged >=30 yrs.
      Among those aged 30-74 yrs, acceptable spirometry was obtained from 6,364 (87%)
      subjects. In a similar survey conducted in 2000-2001, comparable spirometry was
      obtained from 5,495 (80%) participants. Airway obstruction was defined as forced
      expiratory volume in 1 s (FEV(1))/forced vital capacity below the lower limit of
      normal and staged for severity on the basis of FEV(1) % predicted. The age
      adjusted prevalence rates of obstruction (stages I-IV) were rather similar in
      both surveys in males (4.7 versus 4.3%; p = 0.25), but were almost significantly
      higher in females in the later survey (2.2 versus 3.1%; p = 0.06). The rates of
      COPD stage II or higher were 3.9% in 1978-1980, and 3.6% in 2000-2001 (p = 0.36)
      for males, and 1.4 and 1.5% (p = 0.93), respectively, for females. In conclusion,
      no significant difference was found in the prevalence of COPD stages II-IV
      between similar population based surveys performed 20 yrs apart. Since COPD is
      mostly mild or moderate there is a strong case for early prevention.

PMID- 20693259
TI  - Numbers of CD25+Foxp3+ T cells that lack the IL-7 receptor are increased intra
      articularly and have impaired suppressive function in RA patients.
AB  - OBJECTIVES: To investigate numbers and function of CD25(+) regulatory T cells
      (Tregs) that lack IL-7 receptor (CD127) expression in RA. METHODS: Numbers of CD4
      T cells expressing either CD25 or CD127, and those co-expressing or lacking both
      CD25 and CD127 were assessed in peripheral blood (PB) of RA patients and healthy
      controls, and in paired samples of SF and PB from RA patients. All T-cell subsets
      were analysed for FoxP3 expression. The anergic state and the capacity to
      suppress CD127(+) proliferating responder T cells were determined. RESULTS:
      Numbers of CD127(-) T cells and CD25(+) Tregs in PB of RA patients were not
      different from controls but significantly increased in SF compared with PB.
      CD25(+) and CD127(-) T cells showed comparable FoxP3 expression. CD127(+) T cells
      hardly expressed FoxP3. PB CD25(+)CD127(-) T cells identified a subset that
      consisted for 75% of FoxP3(+) cells. SF CD25(+)CD127(-) T-cell number was
      increased; however, in SF fewer of these cells were FoxP3(+). CD25(+)CD127(-) T
      cells were anergic, and in controls potent suppressors of CD127(+) proliferating
      T cells, but in RA patients these cells showed impaired suppression. In line with
      this, IL-7 had an increased capacity to activate total CD4 T cells from SF as
      compared with PB despite increased numbers of CD25(+)CD127(-) in SF. CONCLUSIONS:
      These data demonstrate improved identification of FoxP3(+) T cells in RA patients
      by the absence of CD127 in addition to CD25 expression. Increased numbers of
      CD25(+)CD127(-) T cells are found in inflamed RA joints, but they have an
      impaired suppressive function, which could contribute to the persistent arthritis
      in these patients.

PMID- 20693260
TI  - Observational cohort studies: lessons learnt from the University of Toronto
      Psoriatic Arthritis Program.
AB  - Observational cohorts have emerged as important resources to study course and
      prognosis of chronic disease, and also facilitate phenotype definition for
      genetic studies. We describe the development and accomplishments of the PsA
      cohort at the University of Toronto as an example of an observational cohort that
      has allowed the description of disease manifestations, course and prognosis of
      PsA. We also describe the development of an international collaboration based on
      this cohort, which will further be used to study the incidence, prevalence and
      predictive factors for the development of PsA among patients with psoriasis.

PMID- 20693261
TI  - United Kingdom Primary Sjogren's Syndrome Registry--a united effort to tackle an
      orphan rheumatic disease.
AB  - Primary SS (pSS) is a multi-system autoimmune disease with a prevalence and
      health economic impact that are comparable with RA. However, pSS research has
      been relatively poorly supported. The creation of a large cohort of clinically
      well-characterized pSS patients will provide a catalyst and valuable resources to
      promote high-quality pSS research. In this review, we will describe the creation
      of such a cohort and the associated research biobank that is currently being
      established in the UK--entitled United Kingdom Primary Sjogren's Syndrome
      Registry (UKPSSR). We will discuss the strengths and weaknesses of the design of
      the registry and highlight the key challenges in the establishment of the
      registry and the strategies that we employ to overcome these barriers. Finally,
      we will consider the future development of the UKPSSR including utilization and
      maintenance of the cohort.

PMID- 20693262
TI  - Arrhythmia and cardiac defects are a feature of spinal muscular atrophy model
      mice.
AB  - Proximal spinal muscular atrophy (SMA) is the leading genetic cause of infant
      mortality. Traditionally, SMA has been described as a motor neuron disease;
      however, there is a growing body of evidence that arrhythmia and/or
      cardiomyopathy may present in SMA patients at an increased frequency. Here, we
      ask whether SMA model mice possess such phenotypes. We find SMA mice suffer from
      severe bradyarrhythmia characterized by progressive heart block and impaired
      ventricular depolarization. Echocardiography further confirms functional cardiac
      deficits in SMA mice. Additional investigations show evidence of both sympathetic
      innervation defects and dilated cardiomyopathy at late stages of disease. Based
      upon these data, we propose a model in which decreased sympathetic innervation
      causes autonomic imbalance. Such imbalance would be characterized by a relative
      increase in the level of vagal tone controlling heart rate, which is consistent
      with bradyarrhythmia and progressive heart block. Finally, treatment with the
      histone deacetylase inhibitor trichostatin A, a drug known to benefit phenotypes
      of SMA model mice, produces prolonged maturation of the SMA heartbeat and an
      increase in cardiac size. Treated mice maintain measures of motor function
      throughout extended survival though they ultimately reach death endpoints in
      association with a progression of bradyarrhythmia. These data represent the novel
      identification of cardiac arrhythmia as an early and progressive feature of
      murine SMA while providing several new, quantitative indices of mouse health.
      Together with clinical cases that report similar symptoms, this reveals a new
      area of investigation that will be important to address as we move SMA
      therapeutics towards clinical success.

PMID- 20693263
TI  - A single-nucleotide variation in a p53-binding site affects nutrient-sensitive
      human SIRT1 expression.
AB  - The SIRTUIN1 (SIRT1) deacetylase responds to changes in nutrient availability and
      regulates mammalian physiology and metabolism. Human and mouse SIRT1 are
      transcriptionally repressed by p53 via p53 response elements in their proximal
      promoters. Here, we identify a novel p53-binding sequence in the distal human
      SIRT1 promoter that is required for nutrient-sensitive SIRT1 transcription. In
      addition, we show that a common single-nucleotide (C/T) variation in this
      sequence affects nutrient deprivation-induced SIRT1 transcription, and calorie
      restriction-induced SIRT1 expression. The p53-binding sequence lies in a region
      of the SIRT1 promoter that also binds the transcriptional repressor
      Hypermethylated-In-Cancer-1 (HIC1). Nutrient deprivation increases occupancy by
      p53, while decreasing occupancy by HIC1, of this region of the promoter. HIC1 and
      p53 compete with each other for promoter occupancy. In comparison with the T
      variation, the C variation disrupts the mirror image symmetry of the p53-binding
      sequence, resulting in decreased binding to p53, decreased nutrient sensitivity
      of the promoter and impaired calorie restriction-stimulated tissue expression of
      SIRT1 and SIRT1 target genes AMPKalpha2 and PGC-1beta. Thus, a common SNP in a
      novel p53-binding sequence in the human SIRT1 promoter affects nutrient-sensitive
      SIRT1 expression, and could have a significant impact on calorie restriction
      induced, SIRT1-mediated, changes in human metabolism and physiology.

PMID- 20693264
TI  - "I think he is in his room playing a video game": parental supervision of young
      elementary-school children at home.
AB  - OBJECTIVES: Using a prospective design, this research examined supervision of
      young elementary-school children at home and how this relates to child injury,
      parent permissiveness, and children's risk-taking propensity. METHODS: Mothers
      reported children's history of injuries and recorded home supervision over a 2
      month interval on a weekly basis. Children independently completed diaries about
      daily events, including injuries. RESULTS: Children spent 24% of time alone,
      mostly supervised intermittently or not at all. Parent permissiveness was
      associated with increased time unsupervised, while children's risk-taking
      propensity was associated with decreased time unsupervised. Greater direct
      supervision was associated with fewer injuries, while more indirect and non
      supervision time emerged as risk factors and were associated with more frequent
      injury. CONCLUSIONS: These results extend those from preschool-aged children and
      suggest that caregiver supervision influences risk of injury across a broad age
      range throughout childhood. Implications for children's safety are discussed.

PMID- 20693265
TI  - Early-stage memory loss support groups: outcomes from a randomized controlled
      clinical trial.
AB  - OBJECTIVES: This article describes results of a randomized controlled trial
      comparing a time-limited early-stage memory loss (ESML) support group program
      conducted by a local Alzheimer's Association chapter to a wait-list (WL) control
      condition. METHODS: One hundred and forty-two dyads were randomized in blocks to
      ESML (n = 96) or WL (n = 46). Mean age of participants was 74.9 years, and mean
      Mini-Mental State Examination was 23.4. The primary outcome was participant's
      quality of life; secondary outcomes included mood, family communication, and
      perceived stress. RESULTS: On the intent-to-treat (ITT) pre-post analysis,
      significant differences were seen in participant quality of life (p < .001),
      depression (p < .01), and family communication (p < .05). Within the care partner
      groups, there was no significant difference between ESML and WL in the ITT
      analysis. A post hoc exploratory examination of changes that were associated with
      improved quality of life in ESML participants revealed significant reductions of
      depressive symptoms and behavior problems (p < .05), improved family
      communication (p < .05), self-efficacy (p < .01), Medical Outcomes Study short
      form (SF-36) role-emotional (p < .05), SF-36 social functioning (p < .05), and SF
      36 mental health components (p < .01) in improvers. DISCUSSION: These results
      support the efficacy of ESML support groups for individuals with dementia.

PMID- 20693266
TI  - Cancer incidence in female cosmetologists and manicurists in California, 1988
      2005.
AB  - Health concerns have been pronounced for cosmetologists and manicurists, who are
      exposed daily to cosmetic products containing known or suspected human
      carcinogens and endocrine disruptors. In this retrospective cohort study, the
      authors used probabilistic record linkage between California's statewide
      cosmetology licensee and cancer surveillance files to identify newly diagnosed
      invasive cancers among female workforce members during 1988-2005. Rate ratios and
      95% confidence intervals for cancer among workforce members compared with the
      general female population in California were estimated via Poisson regression.
      For comparison, site-specific proportional incidence ratios were computed. The
      authors identified 9,044 cancer cases in a cohort of 325,228 licensees. Rate
      ratios for all sites combined suggested lower incidence among both cosmetologists
      (rate ratio = 0.84, 95% confidence interval (CI): 0.82, 0.86) and manicurists
      (rate ratio = 0.87, 95% CI: 0.84, 0.90). Proportional incidence ratios were
      modestly elevated for thyroid cancer among all licensees (proportional incidence
      ratio = 1.13, 95% CI: 1.04, 1.23) and for lung cancer among manicurists
      (proportional incidence ratio = 1.21, 95% CI: 1.07, 1.36). Although there did not
      appear to be a cancer excess, these findings may be artifactually influenced by
      limitations in demographic information available from the licensee files.
      Additionally, the relatively young ages of cohort members and demographic shifts
      in the industry composition in recent years suggest a need for further follow-up.

PMID- 20693267
TI  - Diet, supplement use, and prostate cancer risk: results from the prostate cancer
      prevention trial.
AB  - The authors examined nutritional risk factors for prostate cancer among 9,559
      participants in the Prostate Cancer Prevention Trial (United States and Canada,
      1994-2003). The presence or absence of cancer was determined by prostate biopsy,
      which was recommended during the trial because of an elevated prostate-specific
      antigen level or an abnormal digital rectal examination and was offered to all
      men at the trial's end. Nutrient intake was assessed using a food frequency
      questionnaire and a structured supplement-use questionnaire. Cancer was detected
      in 1,703 men; 127 cancers were high-grade (Gleason score 8-10). There were no
      associations of any nutrient or supplement with prostate cancer risk overall.
      Risk of high-grade cancer was associated with high intake of polyunsaturated fats
      (quartile 4 vs. quartile 1: odds ratio = 2.41, 95% confidence interval (CI):
      1.33, 4.38). Dietary calcium was positively associated with low-grade cancer but
      inversely associated with high-grade cancer (for quartile 4 vs. quartile 1, odds
      ratios were 1.27 (95% CI: 1.02, 1.57) and 0.43 (95% CI: 0.21, 0.89),
      respectively). Neither dietary nor supplemental intakes of nutrients often
      suggested for prostate cancer prevention, including lycopene, long-chain n-3
      fatty acids, vitamin D, vitamin E, and selenium, were significantly associated
      with cancer risk. High intake of n-6 fatty acids, through their effects on
      inflammation and oxidative stress, may increase prostate cancer risk.

PMID- 20693268
TI  - Cadmium and peripheral arterial disease: gender differences in the 1999-2004 US
      National Health and Nutrition Examination Survey.
AB  - Gender differences in the association of blood and urine cadmium concentrations
      with peripheral arterial disease (PAD) were evaluated by using data from 6,456 US
      adults aged >=40 years who participated in the 1999-2004 National Health and
      Nutrition Examination Survey. PAD was defined as an ankle-brachial blood pressure
      index of <0.9 in at least one leg. For men, the adjusted odds ratios for PAD
      comparing the highest with the lowest quintiles of blood and urine cadmium
      concentrations were 1.82 (95% confidence interval (CI): 0.82, 4.05) and 4.90 (95%
      CI: 1.55, 15.54), respectively, with a progressive dose-response relation and no
      difference by smoking status. For women, the corresponding odds ratios were 1.19
      (95% CI: 0.66, 2.16) and 0.56 (95% CI: 0.18, 1.71), but there was evidence of
      effect modification by smoking: among women ever smokers, there was a positive,
      progressive dose-response relation; among women never smokers, there was a U
      shaped dose-response relation. Higher blood and urine cadmium levels were
      associated with increased prevalence of PAD, but women never smokers showed a U
      shaped relation with increased prevalence of PAD at very low cadmium levels.
      These findings add to the concern of increased cadmium exposure as a
      cardiovascular risk factor in the general population.

PMID- 20693269
TI  - Folliculogenesis and oogenesis: from basic science to the clinic.

PMID- 20693270
TI  - CCR5 blockade in rheumatoid arthritis: a randomised, double-blind, placebo
      controlled clinical trial.
AB  - OBJECTIVE: C-C chemokine receptor type 5 (CCR5), a chemokine receptor expressed
      on T cells and macrophages, and its ligands are found in inflamed synovial tissue
      (ST) of patients with rheumatoid arthritis (RA). The rationale for testing CCR5
      blockade in patients with RA was supported by the effects of a CCR5 antagonist in
      collagen-induced arthritis in rhesus monkeys. The effects of CCR5 blockade in
      patients with active RA were explored. METHODS: In this phase Ib randomised,
      placebo-controlled trial, treatment with an oral CCR5 inhibitor (SCH351125) in
      patients with active RA was evaluated. Clinical efficacy was assessed using
      European League Against Rheumatism and American College of Rheumatology response
      criteria. ST biopsies were taken before and after 28 days of treatment, and
      analysed for CCR5+ cells. In a subset of patients, MRIs of an inflamed joint were
      obtained before and after treatment. RESULTS: In all, 32 patients were included;
      20 received SCH351125 and 12 placebo. Three patients who received SCH351125 did
      not complete the study due to adverse events; none of these were serious. No
      improvement was observed in the active treatment group compared to placebo.
      Results were consistent for clinical evaluation, ST analysis and MRI. CONCLUSION:
      This proof of concept study does not support the use of CCR5 blockade as a
      therapeutic strategy in patients with active RA.

PMID- 20693271
TI  - Structural and inflammatory sonographic findings in erosive and non-erosive
      osteoarthritis of the interphalangeal finger joints.
AB  - OBJECTIVE: The objectives were: (1) to determine if ultrasound (US) can detect
      more erosions in erosive osteoarthritis (EOA) of the interphalangeal (IP) joints
      than conventional radiography (CR); and (2) to explore the frequency of
      structural and inflammatory findings in EOA and non-EOA. METHODS: Structural
      changes and the anatomical phase were scored on CR in IP joints of 31 patients
      with EOA and 7 patients with non-EOA. Structural and inflammatory changes were
      scored by US. The frequency of sonographic findings was compared between the
      anatomical phases and between EOA and non-EOA by generalised estimation equation
      (GEE) modelling. RESULTS: US detected 68 of 72 (94.4%) erosions seen on CR. US
      detected 45 additional erosive joints in EOA. The frequency of joint effusion and
      power Doppler signal was similar in EOA compared to non-EOA (p = 0.91 and p =
      0.68, respectively). Statistically significantly more synovitis was present in
      full erosive phase compared to non-erosive phases in EOA (p=0.04). No differences
      in inflammatory findings were found between non-erosive phases in EOA and non
      EOA. CONCLUSION: US is capable of detecting erosions in radiographic non-erosive
      phases. The highest frequency of synovitis is present in erosive joints but
      inflammatory findings are common in all anatomical phases of EOA and non-EOA.

PMID- 20693272
TI  - Lipophilic statins prevent matrix metalloproteinase-mediated cartilage collagen
      breakdown by inhibiting protein geranylgeranylation.
AB  - OBJECTIVE: To investigate if statins prevent cartilage degradation and the
      production of collagenases and gelatinases in bovine nasal and human articular
      cartilage after proinflammatory cytokine stimulation. METHODS: In a cartilage
      degradation model, the effects of several statins were assessed by measuring
      proteoglycan degradation and collagen degradation, while collagenolytic and
      gelatinolytic activity in culture supernatants were determined by collagen
      bioassay and gelatin zymography. The production of matrix metalloproteinases
      (MMPs) in cartilage and chondrocytes were analysed by real-time reverse
      transcriptase PCR and immunoassay. Cytokine-induced signalling pathway activation
      was studied by immunoblotting. RESULTS: Simvastatin and mevastatin significantly
      inhibited interleukin 1 (IL-1)+oncostatin M (OSM)-induced collagen degradation;
      this was accompanied with a marked decrease in collagenase and gelatinase
      activity from bovine nasal cartilage. The cholesterol pathway intermediate
      mevalonic acid reversed the simvastatin-mediated protection of cartilage
      degradation, and the expression and production of collagenase (MMP-1 and MMP-13)
      and gelatinase (MMP-2 and MMP-9). Statins also significantly decreased MMP-1 and
      MMP-13 expression in human articular cartilage and chondrocytes stimulated with
      IL-1+OSM, and blocked the activation of critical proinflammatory signalling
      pathways required for MMP expression. The loss of the isoprenoid intermediate
      geranylgeranyl pyrophosphate due to statin treatment accounted for the inhibition
      of MMP expression and signalling pathway activation. CONCLUSIONS: This study
      shows, for the first time, that lipophilic statins are able to block cartilage
      collagen breakdown induced by proinflammatory cytokines, by downregulating key
      cartilage-degrading enzymes. This demonstrates a possible therapeutic role for
      statins in acting as anti-inflammatory agents and in protecting cartilage from
      damage in joint diseases.

PMID- 20693273
TI  - Monitoring adverse events of low-dose glucocorticoid therapy: EULAR
      recommendations for clinical trials and daily practice.
AB  - OBJECTIVE: To develop recommendations on monitoring for adverse events (AEs) of
      low-dose glucocorticoid (GC) therapy (<=7.5 mg prednisone or equivalent daily) in
      clinical trials and daily practice. METHODS: Literature was searched for articles
      containing information on incidence and monitoring of GC-related AEs using
      PubMed, EMBASE and Cochrane databases. Second, the authors searched for broad
      accepted guidelines on the monitoring of certain AEs (eg, WHO guidelines on
      screening for diabetes). Available data were summarised and discussed among
      experts (rheumatologists and patients) of the EULAR Task Force to decide which
      potential AEs should be monitored, how and at which interval. RESULTS: Data on
      monitoring proved to be scarce; most articles were focused on therapeutic effects
      of GCs, not on occurrence and monitoring of AEs. Most recommendations had to be
      based on consensus. Those for clinical trials aimed at getting insights into
      incidence, prevalence and clinical relevance of AEs to create a comprehensive and
      valid AE-profile of GC therapy. The set of AEs to monitor is therefore more
      extensive, and often consists of assessments at baseline and at end of trials.
      Recommendations for daily practice are meant to protect patients from real
      dangers, which can be prevented or treated. Standard care monitoring needs NOT be
      extended for patients on low-dose GC therapy, except for osteoporosis (follow
      national guidelines), and baseline assessments of ankle edema, fasting blood
      glucose and risk factors for glaucoma. CONCLUSION: Given the incompleteness of
      literature data, consensus-based recommendations on monitoring for GC-related AEs
      were created, separately for daily practice and clinical trials.

PMID- 20693274
TI  - Decrease in sick leave among patients with rheumatoid arthritis in the first 12
      months after start of treatment with tumour necrosis factor antagonists: a
      population-based controlled cohort study.
AB  - OBJECTIVE: To investigate the effect of tumour necrosis factor (TNF) antagonist
      treatment of patients with rheumatoid arthritis (RA) on sick leave (SL) and
      disability pension (DP) in a population-based setting in southern Sweden.
      METHODS: All patients with RA in the South Swedish Arthritis Treatment Group
      register living in the county of Skane (population 1.2 million), who started
      their first treatment with a TNF antagonist between January 2004 and December
      2007 and were 18-58 years at treatment start (n = 365), were identified. For each
      patient with RA, four matched reference subjects from the general population were
      randomly selected. Data were linked to the Swedish Social Insurance Agency
      register and the point prevalence of SL and DP as well as days of SL and DP per
      month were calculated from 360 days before until 360 days after treatment start.
      RESULTS: At treatment start 38.6% of the patients with RA were registered for SL.
      During the first 6 months this share dropped to 28.5% (decrease by 26.2%, p<
      0.001). This level remained stable throughout the first treatment year. Comparing
      patients with RA to the reference group the relative risk of being on SL was 6.6
      (95% CI 5.2 to 8.5) at initiation of anti-TNF treatment and 5.2 (95% CI 4.0 to
      6.8) 1 year after that. The corresponding figures for DP were 3.4 (95% CI 2.7 to
      4.2) and 3.2 (95% CI 2.7 to 3.9). CONCLUSIONS: There was a marked decline in SL
      during the first 6 months of TNF antagonist treatment in patients with RA in
      southern Sweden, maintained throughout the first year, which was not offset by a
      corresponding increase in DP.

PMID- 20693275
TI  - Spatiotemporal regulation of multiple overlapping sense and novel natural
      antisense transcripts at the Nrgn and Camk2n1 gene loci during mouse cerebral
      corticogenesis.
AB  - Nrgn and Camk2n1 are highly expressed in the brain and play an important role in
      synaptic long-term potentiation via regulation of Ca(2+)/calmodulin-dependent
      protein kinase II. We have shown that the gene loci for these 2 proteins are
      actively transcribed in the adult cerebral cortex and feature multiple
      overlapping transcripts in both the sense and antisense orientations with
      alternative polyadenylation. These transcripts were upregulated in the adult
      compared with embryonic and P1.5 mouse cerebral cortices, and transcripts with
      different 3' untranslated region lengths showed differing expression profiles. In
      situ hybridization (ISH) analysis revealed spatiotemporal regulation of the Nrgn
      and Camk2n1 sense and natural antisense transcripts (NATs) throughout cerebral
      corticogenesis. In addition, we also demonstrated that the expression of these
      transcripts was organ-specific. Both Nrgn and Camk2n1 sense and NATs were also
      upregulated in differentiating P19 teratocarcinoma cells. RNA fluorescent ISH
      analysis confirmed the capability of these NATs to form double-stranded RNA
      aggregates with the sense transcripts in the cytoplasm of cells obtained from the
      brain. We propose that the differential regulation of multiple sense and novel
      overlapping NATs at the Nrgn and Camk2n1 loci will increase the diversity of
      posttranscriptional regulation, resulting in cell- and time-specific regulation
      of their gene products during cerebral corticogenesis and function.

PMID- 20693276
TI  - Eating without a nose: olfactory dysfunction and sensory-specific satiety.
AB  - Odor stimuli play an important role in the perception of food flavor. Olfactory
      dysfunction is thus likely to affect eating behavior. In the present study, we
      hypothesized that dysfunctional olfactory perception promotes sensory-specific
      satiety, a decrease in pleasure derived from a certain test food during and
      shortly after its consumption relative to other unconsumed control foods. A total
      of 34 hyposmic/anosmic participants were compared with 29 normosmic control
      participants. All participants repeatedly consumed a fixed portion of one and the
      same food item, a procedure known to induce sensory satiation. We found evidence
      for sensory-specific satiety (SSS) regardless of olfactory function. It thus
      appears that olfactory deficits have no major effect on SSS.

PMID- 20693278
TI  - Microtubule-targeted chemotherapeutic agents inhibit signal transducer and
      activator of transcription 3 (STAT3) signaling.
AB  - The transcription factor signal transducer and activator of transcription 3
      (STAT3) is inappropriately activated in the majority of breast tumors, especially
      in aggressive and invasive ones. In addition to driving the expression of genes
      promoting malignancy, STAT3 associates with tubulin and can promote cell
      migration. Because microtubule-targeted drugs are among the most active agents
      used in the treatment of breast cancer, we examined whether microtubule-based
      chemotherapy modulates STAT3 activity. When treated with paclitaxel or
      vinorelbine, breast cancer cells with constitutive activation of STAT3 display a
      loss of STAT3 phosphorylation, and paclitaxel disrupts the interaction of STAT3
      with tubulin. Paclitaxel also inhibits cytokine-induced STAT3 activation. This
      effect is specific for microtubule-targeted agents, because other
      chemotherapeutic drugs, such as doxorubicin, have no effect on STAT3. The loss of
      STAT3 tyrosine phosphorylation is also reflected in an inhibition of expression
      of STAT3 target genes. This effect is not restricted to breast cancer, because
      similar effects are also seen in ovarian cancer and prostate cancer cells. Thus,
      in addition to their role in disrupting microtubule function, microtubule
      targeted agents also suppress STAT3 signaling. This may be an important component
      of their activity, raising the possibility that microtubule targeted therapy may
      be particularly effective in tumors characterized by STAT3 activation.

PMID- 20693277
TI  - Determination of odor detection threshold in the Gottingen minipig.
AB  - The aim of the study was to examine the ability of Gottingen minipigs to acquire
      an olfaction-based operant conditioning task and to determine the detection
      threshold for ethyl acetate and ethanol. We used an automated olfactometer
      developed for rodents to train and test 14 pigs. Odor sampling and reliable
      responding were obtained after three to fifteen 160-trial sessions. Successful
      transfer of the task from ethyl acetate to ethanol was achieved in 1-4 sessions.
      Detection threshold for ethyl acetate varied between 10(-2)% and 10(-6)% v/v and
      for ethanol between 0.1% and 5 * 10(-6)% v/v. The results provide evidence that
      minipigs can successfully acquire 2-odorant discrimination using a food-rewarded
      instrumental conditioning paradigm for testing olfactory function. This olfactory
      discrimination paradigm provides reliable measures of olfactory sensitivity and
      thereby enables detection of changes in olfaction in a porcine model of
      Alzheimer's disease currently being developed.

PMID- 20693279
TI  - Lyn kinase-dependent regulation of miR181 and myeloid cell leukemia-1 expression:
      implications for drug resistance in myelogenous leukemia.
AB  - Imatinib, a BCR-Abl inhibitor, is a successful front-line treatment for chronic
      myelogenous leukemia (CML). Despite the success of imatinib, multiple mechanisms
      of resistance remain a problem, including overexpression of Lyn kinase (Lyn) and
      Bcl-2 family antiapoptotic proteins. Profiling micro-RNA (miRNA) expression in a
      model of Lyn-mediated imatinib-resistant CML (MYL-R) identified approximately 30
      miRNAs whose expression differed >2-fold compared with drug-sensitive MYL cells.
      In particular, the expression of the miR181 family (a-d) was significantly
      reduced (~11- to 25-fold) in MYL-R cells. Incubation of MYL-R cells with a Lyn
      inhibitor (dasatinib) or nucleofection with Lyn-targeting short interfering RNA
      increased miR181b and miR181d expression. A similar Lyn-dependent regulation of
      miR181b and miR181d was observed in imatinib-resistant K562 CML cells. Sequence
      analysis of potential targets for miR181 regulation predicted myeloid cell
      leukemia-1 (Mcl-1), a Bcl-2 family member whose expression is increased in MYL-R
      cells and drug-resistant leukemias. Inhibition of Lyn or rescue of miR181b
      expression reduced Mcl-1 expression in the MYL-R cells. To further investigate
      the mechanism of Mcl-1 repression by miR181, a luciferase reporter construct
      incorporating the Mcl-1 3'-untranslated region was tested. Overexpression of
      miR181b reduced luciferase activity, whereas these effects were ablated by the
      mutation of the seed region of the miR181 target site. Finally, stimulation of
      Lyn expression by 1,25-dihydroxyvitamin D(3) treatment in HL-60 cells, a cell
      model of acute myelogenous leukemia, decreased miR181b expression and increased
      Mcl-1 expression. In summary, our results suggest that Lyn-dependent regulation
      of miR181 is a novel mechanism of regulating Mcl-1 expression and cell survival.

PMID- 20693280
TI  - Membrane curvature induction and tubulation are common features of synucleins and
      apolipoproteins.
AB  - Synucleins and apolipoproteins have been implicated in a number of membrane and
      lipid trafficking events. Lipid interaction for both types of proteins is
      mediated by 11 amino acid repeats that form amphipathic helices. This similarity
      suggests that synucleins and apolipoproteins might have comparable effects on
      lipid membranes, but this has not been shown directly. Here, we find that alpha
      synuclein, beta-synuclein, and apolipoprotein A-1 have the conserved functional
      ability to induce membrane curvature and to convert large vesicles into highly
      curved membrane tubules and vesicles. The resulting structures are
      morphologically similar to those generated by amphiphysin, a curvature-inducing
      protein involved in endocytosis. Unlike amphiphysin, however, synucleins and
      apolipoproteins do not require any scaffolding domains and curvature induction is
      mediated by the membrane insertion and wedging of amphipathic helices alone.
      Moreover, we frequently observed that alpha-synuclein caused membrane structures
      that had the appearance of nascent budding vesicles. The ability to function as a
      minimal machinery for vesicle budding agrees well with recent findings that alpha
      synuclein plays a role in vesicle trafficking and enhances endocytosis. Induction
      of membrane curvature must be under strict regulation in vivo; however, as we
      find it can also cause disruption of membrane integrity. Because the degree of
      membrane curvature induction depends on the concerted action of multiple
      proteins, controlling the local protein density of tubulating proteins may be
      important. How cellular safeguarding mechanisms prevent such potentially toxic
      events and whether they go awry in disease remains to be determined.

PMID- 20693281
TI  - Sulfoacetate is degraded via a novel pathway involving sulfoacetyl-CoA and
      sulfoacetaldehyde in Cupriavidus necator H16.
AB  - Bacterial degradation of sulfoacetate, a widespread natural product, proceeds via
      sulfoacetaldehyde and requires a considerable initial energy input. Whereas the
      fate of sulfoacetaldehyde in Cupriavidus necator (Ralstonia eutropha) H16 is
      known, the pathway from sulfoacetate to sulfoacetaldehyde is not. The genome
      sequence of the organism enabled us to hypothesize that the inducible pathway,
      which initiates sau (sulfoacetate utilization), involved a four-gene cluster
      (sauRSTU; H16_A2746 to H16_A2749). The sauR gene, divergently orientated to the
      other three genes, probably encodes the transcriptional regulator of the presumed
      sauSTU operon, which is subject to inducible transcription. SauU was tentatively
      identified as a transporter of the major facilitator superfamily, and SauT was
      deduced to be a sulfoacetate-CoA ligase. SauT was a labile protein, but it could
      be separated and shown to generate AMP and an unknown, labile CoA-derivative from
      sulfoacetate, CoA, and ATP. This unknown compound, analyzed by MALDI-TOF-MS, had
      a relative molecular mass of 889.7, which identified it as protonated sulfoacetyl
      CoA (calculated 889.6). SauS was deduced to be sulfoacetaldehyde dehydrogenase
      (acylating). The enzyme was purified 175-fold to homogeneity and characterized.
      Peptide mass fingerprinting confirmed the sauS locus (H16_A2747). SauS converted
      sulfoacetyl-CoA and NADPH to sulfoacetaldehyde, CoA, and NADP(+), thus confirming
      the hypothesis.

PMID- 20693282
TI  - Alternative splicing and polyadenylation contribute to the generation of hERG1 C
      terminal isoforms.
AB  - The human ether-a-go-go-related gene 1 (hERG1) encodes the pore-forming subunit
      of the rapidly activating delayed rectifier potassium channel. Several hERG1
      isoforms with different N- and C-terminal ends have been identified. The hERG1a,
      hERG1b, and hERG1-3.1 isoforms contain the full-length C terminus, whereas the
      hERG1(USO) isoforms, hERG1a(USO) and hERG1b(USO), lack most of the C-terminal
      domain and contain a unique C-terminal end. The mechanisms underlying the
      generation of hERG1(USO) isoforms are not understood. We show that hERG1 isoforms
      with different C-terminal ends are generated by alternative splicing and
      polyadenylation of hERG1 pre-mRNA. We identified an intrinsically weak,
      noncanonical poly(A) signal, AGUAAA, within intron 9 of hERG1 that modulates the
      expression of hERG1a and hERG1a(USO). Replacing AGUAAA with the strong, canonical
      poly(A) signal AAUAAA resulted in the predominant production of hERG1a(USO) and a
      marked decrease in hERG1 current. In contrast, eliminating the intron 9 poly(A)
      signal or increasing the strength of 5' splice site led to the predominant
      production of hERG1a and a significant increase in hERG1 current. We found
      significant variation in the relative abundance of hERG1 C-terminal isoforms in
      different human tissues. Taken together, these findings suggest that post
      transcriptional regulation of hERG1 pre-mRNA may represent a novel mechanism to
      modulate the expression and function of hERG1 channels.

PMID- 20693283
TI  - Power of yeast for analysis of eukaryotic translation initiation.

PMID- 20693284
TI  - Translational control mechanisms in long-lasting synaptic plasticity and memory.

PMID- 20693285
TI  - Palmitoylation of the S0-S1 linker regulates cell surface expression of voltage-
      and calcium-activated potassium (BK) channels.
AB  - S-palmitoylation is rapidly emerging as an important post-translational mechanism
      to regulate ion channels. We have previously demonstrated that large conductance
      calcium- and voltage-activated potassium (BK) channels are palmitoylated within
      an alternatively spliced (STREX) insert. However, these studies also revealed
      that additional site(s) for palmitoylation must exist outside of the STREX
      insert, although the identity or the functional significance of these
      palmitoylated cysteine residues are unknown. Here, we demonstrate that BK
      channels are palmitoylated at a cluster of evolutionary conserved cysteine
      residues (Cys-53, Cys-54, and Cys-56) within the intracellular linker between the
      S0 and S1 transmembrane domains. Mutation of Cys-53, Cys-54, and Cys-56
      completely abolished palmitoylation of BK channels lacking the STREX insert (ZERO
      variant). Palmitoylation allows the S0-S1 linker to associate with the plasma
      membrane but has no effect on single channel conductance or the calcium/voltage
      sensitivity. Rather, S0-S1 linker palmitoylation is a critical determinant of
      cell surface expression of BK channels, as steady state surface expression levels
      are reduced by ~55% in the C53:54:56A mutant. STREX variant channels that could
      not be palmitoylated in the S0-S1 linker also displayed significantly reduced
      cell surface expression even though STREX insert palmitoylation was unaffected.
      Thus our work reveals the functional independence of two distinct palmitoylation
      dependent membrane interaction domains within the same channel protein and
      demonstrates the critical role of S0-S1 linker palmitoylation in the control of
      BK channel cell surface expression.

PMID- 20693286
TI  - Protein kinase B (AKT) mediates phospholipase D activation via ERK1/2 and
      promotes respiratory burst parameters in formylpeptide-stimulated neutrophil-like
      HL-60 cells.
AB  - Phospholipase D (PLD), a major source of lipid second messengers (phosphatidic
      acid, diglycerides) in many cell types, is tightly regulated by protein kinases,
      but only a few of them have been identified. We show here that protein kinase B
      (AKT) is a novel major signaling effector of PLD activity induced by the
      formylpeptide f-Met-Leu-Phe (fMLP) in human neutrophil-like HL-60 cells (dHL-60
      cells). AKT inhibition with the selective antagonist AKTib1/2 almost completely
      prevented fMLP-mediated activity of PLD, its upstream effector ERK1/2, but not
      p38 MAPK. Immunoprecipitation studies show that phosphorylated AKT, ERK, and PLD2
      form a complex induced by fMLP, which can be prevented by AKTib1/2. In cell-free
      systems, AKT1 stimulated PLD activity via activation of ERK. AKT1 actually
      phosphorylated ERK2 as a substrate (K(m) 1 MUm). Blocking AKT activation with
      AKTib1/2 also prevented fMLP- but not phorbol 12-myristate 13-acetate-mediated
      NADPH oxidase activation (respiratory burst, RB) of dHL-60 cells. Impaired RB was
      associated with defective membrane translocation of NADPH oxidase components
      p67(phox) and p47(phox), ERK, AKT1, AKT2, but not AKT3. Depletion of AKT1 or AKT2
      with antisense oligonucleotides further indicates a partial contribution of both
      isoforms in fMLP-induced activation of ERK, PLD, and RB, with a predominant role
      of AKT1. Thus, formylpeptides induce sequential activation of AKT, ERK1/2, and
      PLD, which represents a novel signaling pathway. A major primarily role of this
      AKT signaling pathway also emerges in membrane recruitment of NOX2 components
      p47(phox), p67(phox), and ERK, which may contribute to assembly and activation of
      the RB motor system, NADPH oxidase.

PMID- 20693287
TI  - Dependence on vitamin K-dependent protein S for eukaryotic cell secretion of the
      beta-chain of C4b-binding protein.
AB  - The anticoagulant vitamin K-dependent protein S (PS) circulates in plasma in two
      forms, 30% free and 70% being bound to the complement regulatory protein C4b
      binding protein (C4BP). The major C4BP isoform consists of 7 alpha-chains and 1
      beta-chain (C4BPbeta(+)), the chains being linked by disulfide bridges. PS binds
      to the beta-chain with high affinity. In plasma, PS is in molar excess over
      C4BPbeta(+) and due to the high affinity, all C4BPbeta(+) molecules contain a
      bound PS. Taken together with the observation that PS-deficient patients have
      decreased levels of C4BPbeta(+), this raises the question of whether PS is
      important for secretion of the beta-chain from the cell. To test this hypothesis,
      HEK293 cells were stably and transiently transfected with beta-chain cDNA in
      combinations with cDNAs for PS and/or the alpha-chain. The concentration of beta
      chains in the medium increased after co-transfection with PS cDNA, but not by
      alpha-chain cDNA, suggesting secretion of the beta-chains from the cells to be
      dependent on concomitant synthesis of PS, but not of the alpha-chains. Thus, beta
      chains that were not disulfide-linked to the alpha-chains were secreted in
      complex with PS, either as monomers or dimers. Pulse-chase demonstrated that the
      complexes between PS and beta-chain were formed intracellularly, in the
      endoplasmic reticulum. In conclusion, our results demonstrate that successful
      secretion of beta-chains depends on intracellular complex formation with PS, but
      not on the alpha-chains. This provides an explanation for the decreased beta
      chain levels observed in PS-deficient patients.

PMID- 20693288
TI  - N-glycosylation gene DPAGT1 is a target of the Wnt/beta-catenin signaling
      pathway.
AB  - Protein N-glycosylation and the Wnt/beta-catenin signaling pathways play critical
      roles in development and cancer. Although N-glycosylation has been shown to
      influence Wnt signaling through its effects on Wnt ligands, it is unclear whether
      the Wnt/beta-catenin pathway impacts protein N-glycosylation. In this study, we
      show that promoters of the first N-glycosylation gene, DPAGT1, from Chinese
      hamster ovary (CHO), Madin-Darby canine kidney (MDCK), and human epidermoid
      carcinoma (A253) cells contain the T-cell factor/lymphoid enhancer-binding factor
      (TCF/LEF) consensus sequence. Treatment of cells with a Wnt activator, lithium
      chloride, up-regulated DPAGT1 transcript levels that correlated with an increase
      in the beta-catenin abundance. Furthermore, exposure of cells to a Wnt receptor
      ligand, Wnt3a, resulted in an increase in the DPAGT1 transcript levels that was
      abrogated by the Wnt inhibitor, Dickkopf-1. DNA mobility shift assays revealed
      specific protein complexes at the DPAGT1 TCF/LEF binding region that were
      competed off with antibodies to either Tcf3/4 or beta-catenin. Chromatin
      immunoprecipitation analysis confirmed the presence of beta-catenin at the DPAGT1
      promoter in vivo. In addition, the DPAGT1 TCF/LEF sequence drove the expression
      of the luciferase reporter gene. Furthermore, up-regulation of DPAGT1 transcripts
      by Wnt3a led to altered N-glycosylation of E-cadherin. Interestingly, the DPAGT1
      TCF/LEF sequence also interacted with gamma-catenin, a close homologue of beta
      catenin, although not in a lithium chloride-dependent manner. Our results provide
      the first evidence that the Wnt/beta-catenin signaling pathway regulates the
      metabolic pathway of protein N-glycosylation by targeting DPAGT1 expression.
      Moreover, they suggest the existence of another regulatory mechanism involving
      the interaction of Tcf with gamma-catenin at the DPAGT1 promoter.

PMID- 20693289
TI  - Genetic dissection of the amyloid precursor protein in developmental function and
      amyloid pathogenesis.
AB  - Proteolytic processing of the amyloid precursor protein (APP) generates large
      soluble APP derivatives, beta-amyloid (Abeta) peptides, and APP intracellular
      domain. Expression of the extracellular sequences of APP or its Caenorhabditis
      elegans counterpart has been shown to be sufficient in partially rescuing the CNS
      phenotypes of the APP-deficient mice and the lethality of the apl-1 null C.
      elegans, respectively, leaving open the question as what is the role of the
      highly conserved APP intracellular domain? To address this question, we created
      an APP knock-in allele in which the mouse Abeta sequence was replaced by the
      human Abeta. A frameshift mutation was introduced that replaced the last 39
      residues of the APP sequence. We demonstrate that the C-terminal mutation does
      not overtly affect APP processing and amyloid pathology. In contrast, crossing
      the mutant allele with APP-like protein 2 (APLP2)-null mice results in similar
      neuromuscular synapse defects and early postnatal lethality as compared with mice
      doubly deficient in APP and APLP2, demonstrating an indispensable role of the APP
      C-terminal domain in these development activities. Our results establish an
      essential function of the conserved APP intracellular domain in developmental
      regulation, and this activity can be genetically uncoupled from APP processing
      and Abeta pathogenesis.

PMID- 20693290
TI  - Cholinergic modulation of excitatory synaptic input integration in hippocampal
      CA1.
AB  - During theta rhythm, the timing of inputs to hippocampal CA1 from the perforant
      path (PP) of the entorhinal cortex and the Schaffer collaterals (SCs) from
      individual CA3 pyramidal neurons can vary within an individual theta period.
      Importantly, during theta rhythms these interactions occur during elevated
      acetylcholine concentrations. Thus, I examined the effect that PP inputs have on
      SC inputs in hippocampal CA1 during cholinergic receptor activation. To do this I
      measured the impact that a single electrical stimulus of the stratum lacunosum
      moleculare (SLM, which contains the PP) had on excitation evoked by stimulation
      of the stratum radiatum (SR, which contains the SC) using voltage-sensitive dye
      imaging, field excitatory postsynaptic potentials and whole cell patch clamping
      in rat hippocampal brain slices. My data showed that SLM stimulation one half a
      theta cycle or less (25-75 ms) before SR stimulation resulted in the summation of
      excitatory events in SR and SP of hippocampal CA1. The summation was unaffected
      by cholinergic receptor activation by carbachol. SLM stimulation one theta cycle
      (150-225 ms) preceding SR stimulation significantly suppressed excitatory events
      measured in SR and SP. This SLM stimulus inhibition of SR-driven excitatory
      events was augmented by carbachol application. The carbachol effect was blocked
      by atropine and SLM-driven suppression of excitatory events was blocked by the
      GABA(B) receptor antagonist CGP 54626. SR field EPSP slopes were unaffected by
      SLM prepulses. Carbachol increased the probability of SR input to drive action
      potential firing in CA1 pyramidal neurons, which was inhibited by SLM prepulses
      (150-225 ms). Together these data provide important information regarding the
      integration of inputs in hippocampal CA1 during theta rhythms. More specifically,
      SR inputs can be differentially gated by SLM feedforward inhibition at varying
      temporal intervals within a theta cycle.

PMID- 20693291
TI  - alpha-Adrenergic vasoconstrictor responsiveness is preserved in the heated human
      leg.
AB  - This study tested the hypothesis that passive leg heating attenuates alpha
      adrenergic vasoconstriction within that limb. Femoral blood flow (FBF, femoral
      artery ultrasound Doppler) and femoral vascular conductance (FVC, FBF/mean
      arterial blood pressure), as well as calf muscle blood flow (CalfBF, 133xenon)
      and calf vascular conductance (CalfVC) were measured during intra-arterial
      infusion of an alpha1-adrenoreceptor agonist, phenylephrine (PE, 0.025 to 0.8 MUg
      kg-1 min-1) and an alpha2-adrenoreceptor agonist, BHT-933 (1.0 to 10 MUg kg-1 min
      1) during normothermia and passive leg heating (water-perfused pant leg). Passive
      leg heating (~46?C water temperature) increased FVC from 4.5 +/- 0.5 to 11.9 +/-
      1.3 ml min-1 mmHg-1 (P < 0.001). Interestingly, CalfBF (1.8+/-0.2 vs. 2.8+/
      0.3mlmin-1 (100 g)-1) and CalfVC (2.0+/-0.3 vs. 3.9+/-0.5mlmin-1 (100 g)-1 mmHg-1
      *100) were also increased by this perturbation (P <0.05 for both). Infusion of PE
      and BHT-933 resulted in greater absolute decreases in FVC during leg heating
      compared to normothermic conditions (maximal decreases in FVC during heating vs.
      normothermia: PE: 7.8 +/- 1.1 vs. 2.8 +/- 0.5 ml min-1 mmHg-1; BHT-933: 8.6 +/-
      1.7 vs. 2.1 +/- 0.4 ml min-1 mmHg-1; P < 0.01 for both). However, the nadir FVC
      during drug infusion was higher during passive leg heating compared to
      normothermic conditions (FVC at highest dose of respective drugs during heating
      vs. normothermic conditions: PE: 3.7 +/- 0.4 vs. 2.0 +/- 0.3 ml min-1 mmHg-1; BHT
      933: 3.8 +/- 0.2 vs. 2.1 +/- 0.3 ml min-1 mmHg-1; P < 0.001 for both). Leg
      heating did not alter the responsiveness of CalfBF or CalfVC to either PE or BHT
      933. Taken together, these observations suggest that local heating does not
      decrease alpha-adrenergic responsiveness.However, heat-induced vasodilatation
      opposes alpha-adrenergic vasoconstriction. Furthermore, passive heating of a limb
      causes not only an increase in skin blood flow but also in muscle blood flow.

PMID- 20693292
TI  - The effect of passive movement training on angiogenic factors and capillary
      growth in human skeletal muscle.
AB  - The effect of a period of passive movement training on angiogenic factors and
      capillarization in skeletal muscle was examined. Seven young males were subjected
      to passive training for 90 min, four times per week in a motor-driven knee
      extensor device that extended one knee passively at 80 cycles min-1. The other
      leg was used as control. Muscle biopsies were obtained from m. v. lateralis of
      both legs before as well as after 2 and 4 weeks of training. After the training
      period, passive movement and active exercise were performed with both legs, and
      muscle interstitial fluid was sampled from microdialysis probes in the thigh.
      After 2 weeks of training there was a 2-fold higher level of Ki-67 positive
      cells, co-localized with endothelial cells, in the passively trained leg which
      was paralleled by an increase in the number of capillaries around a fibre (P
      <0.05). Capillary density was higher than pre-training at 4 weeks of training (P
      <0.05). The training induced an increase in the mRNA level of endothelial nitric
      oxide synthase (eNOS), the angiopoietin receptor Tie-2 and matrix
      metalloproteinase (MMP)-9 in the passively trained leg and MMP-2 and tissue
      inhibitor of MMP (TIMP)-1 mRNA were elevated in both legs. Acute passive movement
      increased (P <0.05) muscle interstitial vascular endothelial growth factor (VEGF)
      levels 4- to 6-fold above rest and the proliferative effect, determined in vitro,
      of the muscle interstitial fluid ~16-fold compared to perfusate. The magnitude of
      increase was similar for active exercise. The results demonstrate that a period
      of passive movement promotes endothelial cell proliferation and angiogenic
      factors and initiates capillarization in skeletal muscle.

PMID- 20693293
TI  - Modulation of single-channel properties of TRPV1 by phosphorylation.
AB  - Activation of TRPV1, the heat and capsaicin receptor, is known to be promoted by
      phosphorylation, but the molecular details are unclear. In the present study we
      recorded from single TRPV1 ion channels using the cell-attached patch clamp
      technique. The influence of capsaicin concentration on the time constants of open
      and closed states demonstrates the existence of at least four closed and three
      open states, and shows that channel opening can occur from partially liganded
      states. Activation of protein kinase C (PKC) promotes channel opening in some
      channels but not others, consistent with some channels being inaccessible to the
      kinase. The changes in open and closed state time constants following activation
      of PKC are equivalent to an increased affinity of capsaicin binding, but other
      arguments suggest that channel opening must be potentiated by downstream changes
      in channel activation rather than by a direct action of phosphorylation on the
      capsaicin binding site. Mutation of functionally important PKC phosphorylation
      sites on TRPV1, or application of staurosporine, a broad-spectrum kinase
      inhibitor, completely inhibited the effect of PKC in enhancing channel open time.
      Staurosporine also inhibited channel activity in the absence of overt PKC
      activation, showing that TRPV1 is partially phosphorylated at rest. This study
      elucidates the mechanism by which phosphorylation by PKC potentiates the
      activation of single TRPV1 ion channels.

PMID- 20693294
TI  - Physiological roles of voltage-gated proton channels in leukocytes.
AB  - Voltage-gated proton channels are designed to extrude large quantities of
      cytosolic acid in response to depolarising voltages. The discovery of the Hvcn1
      gene and the generation of mice lacking the channel molecule have confirmed
      several postulated functions of proton channels in leukocytes. In neutrophils and
      macrophages, proton channels are required for high-level production of superoxide
      anions by the phagocytic NADPH oxidase, a bactericidal enzyme essential for host
      defence against infections. In B lymphocytes, proton channels are required for
      low-level production of superoxide that boosts the production of antibodies.
      Proton channels sustain the activity of immune cells in several ways. By
      extruding excess cytosolic acid, proton channels prevent deleterious
      acidification of the cytosol and at the same time deliver protons required for
      chemical conversion of the superoxide secreted by membrane oxidases. By moving
      positive charges across membranes, proton channels limit the depolarisation of
      the plasma membrane, promoting the electrogenic activity of NADPH oxidases and
      the entry of calcium ions into cells. Acid extrusion by proton channels is not
      restricted to leukocytes but also mediates the intracellular alkalinisation
      required for the activation of spermatozoids. Proton channels are therefore
      multitalented channels that control male fertility as well as our innate and
      adaptive immunity.

PMID- 20693295
TI  - Prenatal protein restriction leads to a disparity between aortic and peripheral
      blood pressure in Wistar male offspring.
AB  - A host of animal studies have been used to model the effects of exposure to a low
      protein diet in utero on adult blood pressure. Collection of systolic blood
      pressure data by the indirect tail-cuff plethysmography method consistently shows
      increased pressures in low protein exposed rodent offspring compared to controls,
      but this technique has been criticised as the associated stress artefacts may
      confound the observed effects. Conversely, radiotelemetry systems allow
      unrestrained and continuous monitoring of blood pressure through the awake and
      sleep phases of the diurnal cycle. In this novel study, we directly compared
      blood pressure parameters in male offspring from low protein and control-fed dams
      measured simultaneously using tail-cuff and radiotelemetry systems. Control rats
      showed a good correlation between tail-cuff and radiotelemetry derived blood
      pressure data. Conversely, low protein males were relatively hypertensive at 8
      weeks of age when measured by tail-cuff, but had significantly lower blood
      pressure than controls at 12 weeks of age when measured by telemetry. Heart rate
      and length of systole did not differ between the two groups. Individual stress
      protocols mimicking those imposed by tail-cuff plethysmography (novel
      environment, heat, restraint, inflation), caused similar increases in blood
      pressure and heart rate in control and low protein animals, ruling out an effect
      of enhanced pressor response to stress following prenatal protein restriction.
      Instead, an increase in peripheral vascular resistance in these animals is
      considered possible. Such a disparity between central and peripheral blood
      pressure measurements could have important clinical implications regarding
      cardiovascular risk assessment and treatment.

PMID- 20693296
TI  - Sensitive measurement of quantity dynamics of FLT3 internal tandem duplication at
      early time points provides prognostic information.
AB  - BACKGROUND: The level of minimal residual disease (MRD) in acute myeloid leukemia
      (AML) at early time points (TPs) may be an important prognostic factor. Although
      internal tandem duplication of FLT3 (FLT3-ITD) as an MRD marker has been
      questioned for its instability based on semi-quantitative methods, we
      hypothesized that FLT3-ITD dynamics measured by sensitive quantitative real-time
      PCR at early TPs before appearance of instability may provide prognostic
      information. PATIENTS AND METHODS: We measured mutant quantity in 493 serial
      samples from 55 patients with a median follow-up time of 64.8 months. The FLT3
      ITD quantities after induction (TP1) and after the first post-induction
      chemotherapy (TP2) were analyzed. RESULTS: We found that lower FLT3-ITD levels at
      TP2 predicted longer overall survival (OS) and disease-free survival (DFS)
      regardless of cytogenetic risk. Multivariate analysis showed that >=3 log
      reduction of FLT3-ITD at TP2 independently predicted better DFS and a trend
      toward better OS. FLT3-ITD disappeared at relapse in 16.7% of patients and none
      in those harboring mutant NPM1 compared with 29.4% in those with wild-type NPM1
      (P = 0.032). CONCLUSIONS: Though the mutation may disappear at relapse in a few
      patients, FLT3-ITD levels at early TPs after chemotherapy provide prognostic
      information. FLT3-ITD is significantly more stable in those with mutant NPM1.

PMID- 20693297
TI  - Fused FDG-PET/contrast-enhanced CT detects occult subdiaphragmatic involvement of
      Hodgkin's lymphoma thereby identifying patients requiring six cycles of
      anthracycline-containing chemotherapy and consolidation radiation of spleen.
AB  - BACKGROUND: Spleen and liver assessment for occult involvement of Hodgkin's
      lymphoma (HL) challenges current staging procedures. PATIENTS AND METHODS: We
      prospectively evaluated event-free survival (EFS) in 103 HL patients staged with
      fused 2-[fluorine-18]fluoro-2-deoxy-D-glucose-positron emission tomography (FDG
      PET)/contrast-enhanced computed tomography (CT) to identify those at greatest
      risk for abdominal relapse. The EFS of this series was compared with that of a
      historical cohort of 100 HL patients staged with separate FDG-PET and diagnostic
      CT acquisitions. RESULTS: Thirty-one of the 103 patients staged with FDG
      PET/contrast-enhanced CT were found to have spleen involvement and 10 patients
      liver involvement, whereas 14 of the 100 patients staged with separate procedures
      were found to have spleen involvement and 3 patients liver involvement. There
      were significantly more intensive treatments (six courses of anthracycline
      containing chemotherapy and spleen radiation) in the fused PET/CT group than in
      the historical cohort (P <= 0.04). At a median follow-up of 27 months, five
      events occurred in the fused PET/CT group (HL relapse, 4 patients; carcinoma, 1
      patient) and 19 events in the historical cohort (HL relapse, 18 patients; acute
      promyelocytic leukemia, 1 patient). Ten of the 18 relapses in the historical
      cohort were localized in the spleen and/or liver area. None of the four relapses
      in the fused PET/CT group was localized below the diaphragm. Thus, FDG
      PET/contrast-enhanced CT-guided treatment resulted in a 95% EFS, whereas separate
      FDG-PET and diagnostic CT-guided treatment resulted in an 81% EFS (P = 0.002).
      CONCLUSION: FDG-PET/contrast-enhanced CT is an accurate frontline single imaging
      diagnostic tool enabling effective tailored treatment in HL patients.

PMID- 20693298
TI  - Histotype predicts the curative potential of radiotherapy: the example of ovarian
      cancers.
AB  - BACKGROUND: To explore the influence of ovarian cancer histotype on the
      effectiveness of adjuvant radiotherapy (RT). METHODS: A review of a population
      based experience included all referred women with no reported macroscopic
      residuum following primary surgery who underwent adjuvant platin-based
      chemotherapy (CT), with or without sequential RT, and for whom it was possible to
      assign histotype according to the contemporary criteria. RESULTS: Seven hundred
      and three subjects were eligible, of these 351 received RT. For those with
      apparent stage I and II tumors, the cohort with clear cell (C), endometrioid (E),
      and mucinous (M) disease who additionally received RT exhibited a 40% reduction
      in disease-specific mortality and a 43% reduction in overall mortality.
      CONCLUSIONS: The curability of those with stage I and II C-, E-, and M-type
      ovarian carcinomas was enhanced by RT-containing adjuvant therapy. This benefit
      did not extend to those with stage III or serous tumors. These findings
      necessitate reassessments of the role of RT and of the nonselective surgical and
      CT approaches that have characterized ovarian cancer care.

PMID- 20693299
TI  - Weekly combination of non-pegylated liposomal doxorubicin and taxane in first
      line breast cancer: wALT trial (phase I-II).
AB  - BACKGROUND: Through different pharmacodynamic-kinetic interactions, weekly
      administration of proved efficacy agents can overcome resistance with lower
      toxicity and greater benefit. Based on this assumption, we designed a phase I-II
      trial with weekly non-pegylated liposomal anthracycline and taxane in first-line
      breast cancer patients. PATIENTS AND METHODS: We enrolled 56 previously untreated
      metastatic breast cancer patients; they were randomly assigned to receive
      paclitaxel (Taxol) (50 mg/mq) or docetaxel (Taxotere) (30 mg/mq) combined with
      non-pegylated liposomal anthracycline (25 mg/mq) on days 1, 8 and 15 every 4
      weeks. The primary end points were the clinical benefit and treatment-related
      toxic effects assessment. Secondary end points were time-to-disease progression
      (TTP) and overall survival (OS). RESULTS: The overall clinical benefit was
      87.04%. World Health Organization G3-4 toxic effects included neutropenia (45%),
      anemia (44%), complete alopecia (83%), severe onycholysis and neuropathy. The 24%
      of patients developed left ventricular ejection fraction reduction but none >10%
      with recover after treatment completion. The median absolute decrease from
      baseline was 1%. Median TTP was 11 months and median OS was 23 months.
      CONCLUSIONS: Combined weekly administration of taxane and non-pegylated liposomal
      anthracycline is well tolerated and clinical benefit data encourage phase III
      study design.

PMID- 20693300
TI  - Long-term follow-up of HER2-overexpressing stage II or III breast cancer treated
      by anthracycline-free neoadjuvant chemotherapy.
AB  - BACKGROUND: Very effective trastuzumab-based primary systemic therapy (PST) can
      be proposed for conservative surgery purpose to human epidermal growth factor
      receptor 2 (HER2)-positive breast cancer (HER2+BC). Long-term follow-up (LTFU)
      warrants further data. PATIENTS AND METHODS: LTFU of patients, with stage II/III
      HER2+BC, treated by trastuzumab associated with docetaxel (Taxotere((r))) and/or
      carboplatin used as anthracycline-free PST was studied. RESULTS: Among 135
      patients, with a median follow-up of 48.3 months [95% confidence interval (CI)
      45.3-52.4 months], the relapse-free survival (RFS) rate was 73.2% (95% CI 63.76%
      to 80.55%) while the overall survival (OS) rate was 91.87% (95% CI 84.23% to
      95.90%). Adjuvant trastuzumab favorably influenced RFS in univariate analysis
      while the pathological nodal invasion unfavorably influenced RFS [Cox
      multivariate analysis (hazard ratio = 2.80, 95% CI 1.36-5.76, P = 0.0052)] and
      OS. Cardiac toxicity was minor (2.2% transient, reversible asymptomatic decrease
      in left ventricular ejection fraction). CONCLUSION: This is the first report of
      LTFU showing that anthracycline-free trastuzumab-based PST combined either with
      docetaxel and/or carboplatin can achieve, without cardiac toxicity, very
      competitive results in terms of pathological complete response, RFS and OS, in
      HER2+BC. The choice of this schedule could be proposed to patients with vascular
      contraindication for anthracyclines or because patient's or physician's
      preference for a taxane-only schedule.

PMID- 20693301
TI  - Eisosome organization in the filamentous ascomycete Aspergillus nidulans.
AB  - Eisosomes are subcortical organelles implicated in endocytosis and have hitherto
      been described only in Saccharomyces cerevisiae. They comprise two homologue
      proteins, Pil1 and Lsp1, which colocalize with the transmembrane protein Sur7.
      These proteins are universally conserved in the ascomycetes. We identify in
      Aspergillus nidulans (and in all members of the subphylum Pezizomycotina) two
      homologues of Pil1/Lsp1, PilA and PilB, originating from a duplication
      independent from that extant in the subphylum Saccharomycotina. In the aspergilli
      there are several Sur7-like proteins in each species, including one strict Sur7
      orthologue (SurG in A. nidulans). In A. nidulans conidiospores, but not in
      hyphae, the three proteins colocalize at the cell cortex and form tightly packed
      punctate structures that appear different from the clearly distinct eisosome
      patches observed in S. cerevisiae. These structures are assembled late during the
      maturation of conidia. In mycelia, punctate structures are present, but they are
      composed only of PilA, while PilB is diffused in the cytoplasm and SurG is
      located in vacuoles and endosomes. Deletion of each of the genes does not lead to
      any obvious growth phenotype, except for moderate resistance to itraconazole. We
      could not find any obvious association between mycelial (PilA) eisosome-like
      structures and endocytosis. PilA and SurG are necessary for conidial eisosome
      organization in ways that differ from those for their S. cerevisiae homologues.
      These data illustrate that conservation of eisosomal proteins within the
      ascomycetes is accompanied by a striking functional divergence.

PMID- 20693302
TI  - Spitzenkorper, exocyst, and polarisome components in Candida albicans hyphae show
      different patterns of localization and have distinct dynamic properties.
AB  - During the extreme polarized growth of fungal hyphae, secretory vesicles are
      thought to accumulate in a subapical region called the Spitzenkorper. The human
      fungal pathogen Candida albicans can grow in a budding yeast or hyphal form. When
      it grows as hyphae, Mlc1 accumulates in a subapical spot suggestive of a
      Spitzenkorper-like structure, while the polarisome components Spa2 and Bud6
      localize to a surface crescent. Here we show that the vesicle-associated protein
      Sec4 also localizes to a spot, confirming that secretory vesicles accumulate in
      the putative C. albicans Spitzenkorper. In contrast, exocyst components localize
      to a surface crescent. Using a combination of fluorescence recovery after
      photobleaching (FRAP) and fluorescence loss in photobleaching (FLIP) experiments
      and cytochalasin A to disrupt actin cables, we showed that Spitzenkorper-located
      proteins are highly dynamic. In contrast, exocyst and polarisome components are
      stably located at the cell surface. It is thought that in Saccharomyces
      cerevisiae exocyst components are transported to the cell surface on secretory
      vesicles along actin cables. If each vesicle carried its own complement of
      exocyst components, then it would be expected that exocyst components would be as
      dynamic as Sec4 and would have the same pattern of localization. This is not what
      we observe in C. albicans. We propose a model in which a stream of vesicles
      arrives at the tip and accumulates in the Spitzenkorper before onward delivery to
      the plasma membrane mediated by exocyst and polarisome components that are more
      stable residents of the cell surface.

PMID- 20693303
TI  - The transcriptional response to encystation stimuli in Giardia lamblia is
      restricted to a small set of genes.
AB  - The protozoan parasite Giardia lamblia undergoes stage differentiation in the
      small intestine of the host to an environmentally resistant and infectious cyst.
      Encystation involves the secretion of an extracellular matrix comprised of cyst
      wall proteins (CWPs) and a beta(1-3)-GalNAc homopolymer. Upon the induction of
      encystation, genes coding for CWPs are switched on, and mRNAs coding for a Myb
      transcription factor and enzymes involved in cyst wall glycan synthesis are
      upregulated. Encystation in vitro is triggered by several protocols, which call
      for changes in bile concentrations or availability of lipids, and elevated pH.
      However, the conditions for induction are not standardized and we predicted
      significant protocol-specific side effects. This makes reliable identification of
      encystation factors difficult. Here, we exploited the possibility of inducing
      encystation with two different protocols, which we show to be equally effective,
      for a comparative mRNA profile analysis. The standard encystation protocol
      induced a bipartite transcriptional response with surprisingly minor involvement
      of stress genes. A comparative analysis revealed a core set of only 18
      encystation genes and showed that a majority of genes was indeed upregulated as a
      side effect of inducing conditions. We also established a Myb binding sequence as
      a signature motif in encystation promoters, suggesting coordinated regulation of
      these factors.

PMID- 20693304
TI  - Endocytic machinery protein SlaB is dispensable for polarity establishment but
      necessary for polarity maintenance in hyphal tip cells of Aspergillus nidulans.
AB  - The Aspergillus nidulans endocytic internalization protein SlaB is essential, in
      agreement with the key role in apical extension attributed to endocytosis. We
      constructed, by gene replacement, a nitrate-inducible, ammonium-repressible slaB1
      allele for conditional SlaB expression. Video microscopy showed that repressed
      slaB1 cells are able to establish but unable to maintain a stable polarity axis,
      arresting growth with budding-yeast-like morphology shortly after initially
      normal germ tube emergence. Using green fluorescent protein (GFP)-tagged
      secretory v-SNARE SynA, which continuously recycles to the plasma membrane after
      being efficiently endocytosed, we establish that SlaB is crucial for endocytosis,
      although it is dispensable for the anterograde traffic of SynA and of the t-SNARE
      Pep12 to the plasma and vacuolar membrane, respectively. By confocal microscopy,
      repressed slaB1 germlings show deep plasma membrane invaginations. Ammonium-to
      nitrate medium shift experiments demonstrated reversibility of the null polarity
      maintenance phenotype and correlation of normal apical extension with resumption
      of SynA endocytosis. In contrast, SlaB downregulation in hyphae that had
      progressed far beyond germ tube emergence led to marked polarity maintenance
      defects correlating with deficient SynA endocytosis. Thus, the strict correlation
      between abolishment of endocytosis and disability of polarity maintenance that we
      report here supports the view that hyphal growth requires coupling of secretion
      and endocytosis. However, downregulated slaB1 cells form F-actin clumps
      containing the actin-binding protein AbpA, and thus F-actin misregulation cannot
      be completely disregarded as a possible contributor to defective apical
      extension. Latrunculin B treatment of SlaB-downregulated tips reduced the
      formation of AbpA clumps without promoting growth and revealed the formation of
      cortical "comets" of AbpA.

PMID- 20693305
TI  - The N terminus of phosphodiesterase TbrPDEB1 of Trypanosoma brucei contains the
      signal for integration into the flagellar skeleton.
AB  - The precise subcellular localization of the components of the cyclic AMP (cAMP)
      signaling pathways is a crucial aspect of eukaryotic intracellular signaling. In
      the human pathogen Trypanosoma brucei, the strict control of cAMP levels by cAMP
      specific phosphodiesterases is essential for parasite survival, both in cell
      culture and in the infected host. Among the five cyclic nucleotide
      phosphodiesterases identified in this organism, two closely related isoenzymes,
      T. brucei PDEB1 (TbrPDEB1) (PDEB1) and TbrPDEB2 (PDEB2) are predominantly
      responsible for the maintenance of cAMP levels. Despite their close sequence
      similarity, they are distinctly localized in the cell. PDEB1 is mostly located in
      the flagellum, where it forms an integral part of the flagellar skeleton. PDEB2
      is mainly located in the cell body, and only a minor part of the protein
      localizes to the flagellum. The current study, using transfection of procyclic
      trypanosomes with green fluorescent protein (GFP) reporters, demonstrates that
      the N termini of the two enzymes are essential for determining their final
      subcellular localization. The first 70 amino acids of PDEB1 are sufficient to
      specifically direct a GFP reporter to the flagellum and to lead to its detergent
      resistant integration into the flagellar skeleton. In contrast, the analogous
      region of PDEB2 causes the GFP reporter to reside predominantly in the cell body.
      Mutagenesis of selected residues in the N-terminal region of PDEB2 demonstrated
      that single amino acid changes are sufficient to redirect the reporter from a
      cell body location to stable integration into the flagellar skeleton.

PMID- 20693306
TI  - Personalized medicine: marking a new epoch in cancer patient management.
AB  - Personalized medicine (PM) is defined as "a form of medicine that uses
      information about a person's genes, proteins, and environment to prevent,
      diagnose, and treat disease." The promise of PM has been on us for years. The
      suite of clinical applications of PM in cancer is broad, encompassing screening,
      diagnosis, prognosis, prediction of treatment efficacy, patient follow-up after
      surgery for early detection of recurrence, and the stratification of patients
      into cancer subgroup categories, allowing for individualized therapy. PM aims to
      eliminate the "one size fits all" model of medicine, which has centered on
      reaction to disease based on average responses to care. By dividing patients into
      unique cancer subgroups, treatment and follow-up can be tailored for each
      individual according to disease aggressiveness and the ability to respond to a
      certain treatment. PM is also shifting the emphasis of patient management from
      primary patient care to prevention and early intervention for high-risk
      individuals. In addition to classic single molecular markers, high-throughput
      approaches can be used for PM including whole genome sequencing, single
      nucleotide polymorphism analysis, microarray analysis, and mass spectrometry. A
      common trend among these tools is their ability to analyze many targets
      simultaneously, thus increasing the sensitivity, specificity, and accuracy of
      biomarker discovery. Certain challenges need to be addressed in our transition to
      PM including assessment of cost, test standardization, and ethical issues. It is
      clear that PM will gradually continue to be incorporated into cancer patient
      management and will have a significant impact on our health care in the future.

PMID- 20693307
TI  - Fecal occult blood testing has great potential as a screening tool for colorectal
      cancer.

PMID- 20693308
TI  - Serum bilirubin and genes controlling bilirubin concentrations as biomarkers for
      cardiovascular disease.
AB  - BACKGROUND: Serum bilirubin has been consistently shown to be inversely related
      to cardiovascular disease (CVD). Recent studies showed serum bilirubin to be
      associated with CVD-related factors such as diabetes, metabolic syndrome, and
      body mass index. Although the association of serum bilirubin with CVD has been
      found in both retrospective and prospective studies, less information is
      available on the role of genes that control bilirubin concentrations and their
      association with CVD. CONTENT: In this review, we provide detailed information on
      the identity of the major genes that control bilirubin concentrations and their
      association with serum bilirubin concentrations and CVD risk. We also update the
      results of the major studies that have been performed on the association between
      serum bilirubin, CVD, and CVD-related diseases such as diabetes or metabolic
      syndrome. Studies consistently indicate that bilirubin concentrations are
      inversely associated with different types of CVD and CVD-related diseases. A
      conditional linkage study indicates that UGT1A1 is the major gene controlling
      serum bilirubin concentrations, and this finding has been confirmed in recent
      genomewide association studies. Studies also indicate that individuals homozygous
      for UGT1A1*28 have a significantly lower risk of developing CVD than carriers of
      the wild-type alleles. SUMMARY: Serum bilirubin has a protective effect on CVD
      and CVD-related diseases, and UGT1A1 is the major gene controlling serum
      bilirubin concentrations. Pharmacologic, nonpharmacologic, or genetic
      interventions that increase serum bilirubin concentrations could provide more
      direct evidence on the role of bilirubin in CVD prevention.

PMID- 20693309
TI  - Libraries of specific assays covering whole proteomes: from yeast to man.

PMID- 20693310
TI  - A prospective study on dietary acrylamide intake and the risk for breast,
      endometrial, and ovarian cancers.
AB  - BACKGROUND: Acrylamide is a probable human carcinogen formed during cooking of
      many common foods. Epidemiologic studies on acrylamide and breast cancer risk
      have been null; however, positive associations with ovarian and endometrial
      cancers have been reported. We studied acrylamide intake and risk for breast,
      endometrial, and ovarian cancers in a prospective cohort study. METHODS: We
      assessed acrylamide intake among 88,672 women in the Nurses' Health Study using
      food frequency questionnaires administered every 4 years. Between 1980 and 2006,
      we identified 6,301 cases of invasive breast cancer, 484 cases of invasive
      endometrial adenocarcinoma, and 416 cases of epithelial ovarian cancer. We used
      Cox proportional hazards models to study the association between acrylamide and
      cancer risk. RESULTS: We found no association between acrylamide intake and
      breast cancer overall or according to estrogen and progesterone receptor status.
      We found an increased risk for endometrial cancer among high acrylamide consumers
      (adjusted relative risk for highest versus lowest quintile = 1.41; 95% CI, 1.01
      1.97; P for trend = 0.03). We observed a nonsignificant suggestion of increased
      risk for ovarian cancer overall (relative risk, 1.25; 95% CI, 0.88-1.77; P trend
      = 0.12), with a significantly increased risk for serous tumors (relative risk,
      1.58; 95% CI, 0.99-2.52; P trend = 0.04). Associations did not differ by smoking
      status. CONCLUSIONS: We observed no association between acrylamide and breast
      cancer. Risk for endometrial cancer and possibly ovarian cancer was greater among
      high acrylamide consumers. IMPACT: This is the second prospective study to report
      positive associations with endometrial and ovarian cancers. These associations
      should be further evaluated to inform public health policy.

PMID- 20693311
TI  - Species delimitation using dominant and codominant multilocus markers.
AB  - We propose a method for delimiting species based on dominant or codominant
      multilocus data using Gaussian clustering with a noise component for outliers.
      Case studies show that provisional species delimited using Gaussian clustering
      based on dominant multilocus data correspond well with provisional species
      delimited based on other data. However, the performance of Gaussian clustering in
      delimiting species based on few codominant markers was only moderate. Species
      represented by few individuals are usually included in the noise component
      because clusters are difficult to recognize with limited data. As alternative
      methods, we evaluated two model-based clustering methods originally proposed to
      infer population structure and assign individuals to populations based on the
      assumption of Hardy-Weinberg equilibrium within populations, namely STRUCTURE and
      STRUCTURAMA, as well as the "fields for recombination" approach. The latter
      resulted in lumping all individuals of each data set with codominant markers
      together, and whereas STRUCTURE often provides no decision about the number of
      clusters, STRUCTURAMA usually yields correct or almost correct numbers of
      clusters. The classification success of STRUCTURAMA analyses based on codominant
      markers was very good, but its performance with dominant markers was less
      consistent. Based on the classification success of the different methods for
      delimiting species with dominant and codominant multilocus markers in the case
      studies, we recommend using Gaussian clustering for data sets with dominant
      markers and STRUCTURAMA for data sets with codominant markers.

PMID- 20693312
TI  - Glucocorticoids potentiate IL-6-induced SP-B expression in H441 cells by
      enhancing the JAK-STAT signaling pathway.
AB  - The respiratory distress syndrome (RDS) contributes to perinatal morbidity and
      mortality associated with preterm birth. Surfactant protein B (SP-B) is decreased
      in RDS. Both maternal antenatal steroid administration and chorioamnionitis
      reduce the incidence and severity of RDS. An important mediator in
      chorioamnionitis is IL-6 using the JAK-STAT signaling pathway for signal
      transduction. We hypothesized that the steroids, betamethasone (BTM) and
      dexamethasone (DXM), and IL-6 had synergistic effects on SP-B gene expression and
      STAT3 phosphorylation in H441 cells. DXM and BTM increased SP-B mRNA levels by
      16.5 (13.3)-fold and IL-6 alone by 2.3-fold. After 48-h exposure of cells to DXM
      or BTM, IL-6 caused a significantly greater increase in SP-B mRNA levels (28.1
      fold) than IL-6 or glucocorticoids alone. Whereas IL-6 stimulated tyrosine
      phosphorylation of STAT3 in a time- and dose-dependent way, DXM and BTM had no
      effect on STAT3 phosphorylation. Both DXM and BTM could potentiate IL-6-induced
      phosphorylation of STAT3. The synergism of glucocorticoids and IL-6 on SP-B gene
      expression and the effect of glucocorticoids on IL-6-induced STAT3
      phosphorylation could be blocked by a JAK inhibitor. Expression level analysis
      showed that glucocorticoids increased the expression of the IL-6-binding alpha
      subunit receptor (IL-6R) on mRNA and protein level. Our findings could represent
      an example of a pulmonary regulation system in which one role of glucocorticoids
      is to increase the effect of a cytokine by upregulation of its receptor. The
      described in vitro interaction of IL-6 and glucocorticoids could help explain the
      clinical observation that prenatal inflammation in preterm babies with antenatal
      steroid administration can attenuate severity of RDS.

PMID- 20693313
TI  - Entrained pulmonary clocks: epithelium and vasculature keeping pace.

PMID- 20693314
TI  - Expression of store-operated Ca2+ entry and transient receptor potential
      canonical and vanilloid-related proteins in rat distal pulmonary venous smooth
      muscle.
AB  - Chronic hypoxia causes remodeling and alters contractile responses in both
      pulmonary arteries and pulmonary veins. Although pulmonary arteries have been
      studied extensively in these disorders, the mechanisms by which pulmonary veins
      respond to hypoxia and whether these responses contribute to chronic hypoxic
      pulmonary hypertension remain poorly understood. In pulmonary arterial smooth
      muscle, we have previously demonstrated that influx of Ca(2+) through store
      operated calcium channels (SOCC) thought to be composed of transient receptor
      potential (TRP) proteins is likely to play an important role in development of
      chronic hypoxic pulmonary hypertension. To determine whether this mechanism could
      also be operative in pulmonary venous smooth muscle, we measured intracellular
      Ca(2+) concentration ([Ca(2+)](i)) by fura-2 fluorescence microscopy in primary
      cultures of pulmonary venous smooth muscle cells (PVSMC) isolated from rat distal
      pulmonary veins. In cells perfused with Ca(2+)-free media containing
      cyclopiazonic acid (10 MUM) and nifedipine (5 MUM) to deplete sarcoplasmic
      reticulum Ca(2+) stores and block voltage-dependent Ca(2+) channels, restoration
      of extracellular Ca(2+) (2.5 mM) caused marked increases in [Ca(2+)](i), whereas
      MnCl(2) (200 MUM) quenched fura-2 fluorescence, indicating store-operated Ca(2+)
      entry (SOCE). SKF-96365 and NiCl(2), antagonists of SOCC, blocked SOCE at
      concentrations that did not alter Ca(2+) responses to 60 mM KCl. Of the seven
      known canonical TRP (TRPC1-7) and six vanilloid-related TRP channels (TRPV1-6),
      real-time PCR revealed mRNA expression of TRPC1 > TRPC6 > TRPC4 > TRPC2 ~ TRPC5 >
      TRPC3, TRPV2 > TRPV4 > TRPV1 in distal PVSMC, and TRPC1 > TRPC6 > TRPC3 > TRPC4 ~
      TRPC5, TRPV2 ~ TRPV4 > TRPV1 in rat distal pulmonary vein (PV) smooth muscle.
      Western blotting confirmed protein expression of TRPC1, TRPC6, TRPV2, and TRPV4
      in both PVSMC and PV. Our results suggest that SOCE through Ca(2+) channels
      composed of TRP proteins may contribute to Ca(2+) signaling in rat distal PV
      smooth muscle.

PMID- 20693315
TI  - A new role for bicarbonate in mucus formation.
AB  - The impact of small anions on the physical properties of gel-forming mucin has
      been almost overlooked relative to that of cations. Recently, based on the
      coincident abnormalities in HCO(3)(-) secretion and abnormal mucus formed in the
      hereditary disease cystic fibrosis (CF), HCO(3)(-) was hypothesized to be
      critical in the formation of normal mucus by virtue of its ability to sequester
      Ca(2+) from condensed mucins being discharged from cells. However, direct
      evidence of the impact of HCO(3)(-) on mucus properties is lacking. Herein, we
      demonstrate for the first time that mucin diffusivity (~1/viscosity) increases as
      a function of [HCO(3)(-)]. Direct measurements of exocytosed mucin-swelling
      kinetics from airway cells showed that mucin diffusivity increases by ~300% with
      20 mM extracellular HCO(3)(-) concentration. Supporting data indicate that
      HCO(3)(-) reduces free Ca(2+) concentration and decreases the amount of Ca(2+)
      that remains associated with mucins. The results demonstrate that HCO(3)(-)
      enhances mucin swelling and hydration by reducing Ca(2+) cross-linking in mucins,
      thereby decreasing its viscosity and likely increasing its transportability. In
      addition, HCO(3)(-) can function as a Ca(2+) chelator like EGTA to disperse mucin
      aggregates. This study indicates that poor HCO(3)(-) availability in CF may
      explain why secreted mucus remains aggregated and more viscous in affected
      organs. These insights bear on not only the fundamental pathogenesis in CF, but
      also on the process of gel mucus formation and release in general.

PMID- 20693316
TI  - Differential induction of CD38 expression by TNF-{alpha} in asthmatic airway
      smooth muscle cells.
AB  - The ADP-ribosyl cyclase activity of CD38, a membrane protein expressed in human
      airway smooth muscle (ASM) cells, generates cyclic ADP-ribose (cADPR), a Ca2(+)
      mobilizing agent. cADPR-mediated Ca2(+) responses to agonists are augmented in
      human ASM cells by TNF-alpha. CD38-deficient mice fail to develop airway
      hyperresponsiveness following intranasal TNF-alpha or IL-13 challenge, suggesting
      a role in asthma. The role of CD38 in human asthma remains unknown. We
      hypothesized that CD38 expression will be elevated in ASM cells from asthmatic
      donors (ASMA cells). CD38 mRNA and ADP-ribosyl cyclase activity were measured in
      cells maintained in growth-arrested conditions and exposed to vehicle or TNF
      alpha (10-40 ng/ml). TNF-alpha-induced induction of CD38 expression was greater
      in ASMA than in ASM cells from nonasthmatic donors (ASMNA). In four of the six
      donors, basal and TNF-alpha-induced ERK and p38 MAPK activation were higher in
      ASMA than ASMNA cells. JNK MAPK activation was lower in ASMA than ASMNA cells.
      Nuclear NF-kappaB (p50 subunit) and phosphorylated c-Jun were comparable in cells
      from both groups, although nuclear c-Fos (part of the AP-1 complex) levels were
      lower in ASMA than ASMNA cells. NF-kappaB or AP-1 binding to their consensus
      sequences was comparable in ASMNA and ASMA cells, as are the decay kinetics of
      CD38 mRNA. The findings suggest that the differential induction of CD38 by TNF
      alpha in ASMA cells is due to increased transcriptional regulation involving ERK
      and p38 MAPK activation and is independent of changes in NF-kappaB or AP-1
      activation. The findings suggest a potential role for CD38 in the pathophysiology
      of asthma.

PMID- 20693317
TI  - MicroRNA-21 plays a role in hypoxia-mediated pulmonary artery smooth muscle cell
      proliferation and migration.
AB  - Hypoxia stimulates pulmonary artery smooth muscle cell (PASMC) proliferation.
      Recent studies have implicated an important role for microRNAs (miRNAs) in
      hypoxia-mediated responses in various cellular processes, including cell
      proliferation. In this study, we investigated the role of microRNA-21 (miR-21) in
      hypoxia-induced PASMC proliferation and migration. We first demonstrated that miR
      21 expression increased by ~3-fold in human PASMC after 6 h of hypoxia (3% O2)
      and remained high (~2-fold) after 24 h of hypoxia. Knockdown of miR-21 with anti
      miR-21 inhibitors significantly reduced hypoxia-induced cell proliferation,
      whereas miR-21 overexpression in normoxia enhanced cell proliferation. We also
      found that miR-21 is essential for hypoxia-induced cell migration. Protein
      expression of miR-21 target genes, specifically programmed cell death protein 4
      (PDCD4), Sprouty 2 (SPRY2), and peroxisome proliferator-activated receptor-alpha
      (PPARalpha), was decreased in hypoxia and in PASMC overexpressing miR-21 in
      normoxia and increased in hypoxic cells in which miR-21 was knocked down. In
      addition, PPARalpha 3'-untranslated region (UTR) luciferase-based reporter gene
      assays demonstrated that PPARalpha is a direct target of miR-21. Taken together,
      our findings indicate that miR-21 plays a significant role in hypoxia-induced
      pulmonary vascular smooth muscle cell proliferation and migration by regulating
      multiple gene targets.

PMID- 20693318
TI  - Human SP-A1 (SFTPA1) variant-specific 3' UTRs and poly(A) tail differentially
      affect the in vitro translation of a reporter gene.
AB  - Human surfactant protein A (SP-A) is encoded by two functional genes (SFTPA1,
      SFTPA2) with a high degree of sequence identity. Sequence differences among these
      genes and their genetic variants have been observed at the 5' and 3' untranslated
      regions (UTRs). In this work, we studied the impact on translation of the SFTPA1
      (hSP-A1) and SFTPA2 (hSP-A2) gene 5' UTR splice variants and 3' UTR sequence
      variants, in the presence or absence of poly(A) tail. We generated constructs
      containing the luciferase reporter gene flanked upstream by one of the hSP-A 5'
      UTR splice variants and/or downstream by one hSP-A 3' UTR sequence variant. mRNA
      transcripts were prepared by in vitro transcription and used for either in vitro
      translation with a rabbit reticulocyte lysate or transient transfection of the
      lung adenocarcinoma cell line NCI-H441. The luciferase activity results indicate
      that hSP-A 5' UTR and 3' UTR together have an additive effect on translation. In
      this context, the hSP-A1 6A(3) and 6A(4) 3' UTR variants exhibited higher
      translation efficiency than the 6A(2) variant (P <0.05), whereas no significant
      difference was observed between the two hSP-A2 3' UTRs studied (1A(0), 1A(3)).
      Further sequence analysis revealed that a deletion of an 11-nucleotide (nt)
      element in both the 6A(3) and 6A(4) 3' UTR variants changes the predicted
      secondary structure stability and the number of putative miRNA binding sites.
      Removal of this 11-nt element in the 6A(2) 3' UTR resulted in increased
      translation, and the opposite effect was observed when the 11-nt element was
      cloned in a guest 3' UTR (6A(3), 6A(4)). These results indicate that sequence
      differences among hSP-A gene variants may account for differential regulation at
      the translational level.

PMID- 20693319
TI  - Role of ROS in ischemia-induced lung angiogenesis.
AB  - Pulmonary artery obstruction and subsequent lung ischemia have been shown to
      induce systemic angiogenesis despite preservation of normoxia. The underlying
      mechanisms, however, remain poorly understood. In a mouse model of lung ischemia
      induced by left pulmonary artery ligation (LPAL), we showed previously, the
      formation of a new systemic vasculature to the ischemic lung. We hypothesize that
      LPAL in the mouse increases reactive oxygen species (ROS) production, and these
      molecules play an initiating role in subsequent lung neovascularization. We used
      oxidant-sensitive dyes (DHE and H(2)DCF-DA) to quantify ROS and measured the
      antioxidant-reduced glutathione (GSH) and its oxidized form (GSSG) as indicators
      of ROS levels after LPAL. The magnitude of systemic neovascularization was
      determined by measuring systemic blood flow to the left lung with radiolabeled
      microspheres 14 days after LPAL. An increase in ROS was observed early (30 min:
      55% increase in H(2)DCF-DA) after LPAL, with a return to baseline by 24 h.
      GSH/GSSG was decreased (~50%) 4 h after LPAL, suggesting earlier ROS
      upregulation. Mice treated with the antioxidant N-acetylcysteine showed
      attenuated angiogenesis (62% of wild-type LPAL), and mice lacking Nrf2, a
      transcription factor important for antioxidant synthesis, resulted in increased
      neovascularization (207% of wild-type LPAL). Overall, GSH/GSSG was inversely
      associated with the magnitude of neovascularization. These results demonstrate
      that LPAL induces an early and transient ROS upregulation, and ROS appear to play
      a role in promoting ischemia-induced angiogenesis.

PMID- 20693320
TI  - Gene function prediction using semantic similarity clustering and enrichment
      analysis in the malaria parasite Plasmodium falciparum.
AB  - MOTIVATION: Functional genomics data provides a rich source of information that
      can be used in the annotation of the thousands of genes of unknown function found
      in most sequenced genomes. However, previous gene function prediction programs
      are mostly produced for relatively well-annotated organisms that often have a
      large amount of functional genomics data. Here, we present a novel method for
      predicting gene function that uses clustering of genes by semantic similarity, a
      naive Bayes classifier and 'enrichment analysis' to predict gene function for a
      genome that is less well annotated but does has a severe effect on human health,
      that of the malaria parasite Plasmodium falciparum. RESULTS: Predictions for the
      molecular function, biological process and cellular component of P.falciparum
      genes were created from eight different datasets with a combined prediction also
      being produced. The high-confidence predictions produced by the combined
      prediction were compared to those produced by a simple K-nearest neighbour
      classifier approach and were shown to improve accuracy and coverage. Finally, two
      case studies are described, which investigate two biological processes in more
      detail, that of translation initiation and invasion of the host cell.
      AVAILABILITY: Predictions produced are available at
      http://www.bioinformatics.leeds.ac.uk/~bio5pmrt/PAGODA.

PMID- 20693321
TI  - Association screening of common and rare genetic variants by penalized
      regression.
AB  - MOTIVATION: This article extends our recent research on penalized estimation
      methods in genome-wide association studies to the realm of rare variants.
      RESULTS: The new strategy is tested on both simulated and real data. Our findings
      on breast cancer data replicate previous results and shed light on variant
      effects within genes. AVAILABILITY: Rare variant discovery by group penalized
      regression is now implemented in the free program Mendel at
      http://www.genetics.ucla.edu/software/.

PMID- 20693322
TI  - RefProtDom: a protein database with improved domain boundaries and homology
      relationships.
AB  - RefProtDom provides a set of divergent query domains, originally selected from
      Pfam, and full-length proteins containing their homologous domains, with diverse
      architectures, for evaluating pair-wise and iterative sequence similarity
      searches. Pfam homology and domain boundary annotations in the target library
      were supplemented using local and semi-global searches, PSI-BLAST searches, and
      SCOP and CATH classifications. AVAILABILITY: RefProtDom is available from
      http://faculty.virginia.edu/wrpearson/fasta/PUBS/gonzalez09a.

PMID- 20693323
TI  - Regulation of autotrophic CO2 fixation in the archaeon Thermoproteus
      neutrophilus.
AB  - Thermoproteus neutrophilus, a hyperthermophilic, chemolithoautotrophic, anaerobic
      crenarchaeon, uses a novel autotrophic CO(2) fixation pathway, the
      dicarboxylate/hydroxybutyrate cycle. The regulation of the central carbon
      metabolism was studied on the level of whole cells, enzyme activity, the
      proteome, transcription, and gene organization. The organism proved to be a
      facultative autotroph, which prefers organic acids as carbon sources that can
      easily feed into the metabolite pools of this cycle. Addition of the preferred
      carbon sources acetate, pyruvate, succinate, and 4-hydroxybutyrate to cultures
      resulted in stimulation of the growth rate and a diauxic growth response. The
      characteristic enzyme activities of the carbon fixation cycle, fumarate
      hydratase, fumarate reductase, succinyl coenzyme A (CoA) synthetase, and enzymes
      catalyzing the conversion of succinyl-CoA to crotonyl-CoA, were differentially
      downregulated in the presence of acetate and, to a lesser extent, in the presence
      of other organic substrates. This regulation pattern correlated well with the
      differential expression profile of the proteome as well as with the transcription
      of the encoding genes. The genes encoding phosphoenolpyruvate (PEP) carboxylase,
      fumarate reductase, and four enzymes catalyzing the conversion of succinyl-CoA to
      crotonyl-CoA are clustered. Two putative operons, one comprising succinyl-CoA
      reductase plus 4-hydroxybutyrate-CoA ligase genes and the other comprising 4
      hydroxybutyryl-CoA dehydratase plus fumarate reductase genes, were divergently
      transcribed into leaderless mRNAs. The promoter regions were characterized and
      used for isolating DNA binding proteins. Besides an Alba protein, a 18-kDa
      protein characteristic for autotrophic Thermoproteales that bound specifically to
      the promoter region was identified. This system may be suitable for molecular
      analysis of the transcriptional regulation of autotrophy-related genes.

PMID- 20693324
TI  - Sit and stay a while: how BfiSR controls irreversible attachment in Pseudomonas
      aeruginosa biofilms.

PMID- 20693325
TI  - A multitask ATPase serving different ABC-type sugar importers in Bacillus
      subtilis.
AB  - Bacillus subtilis is able to utilize arabinopolysaccharides derived from plant
      biomass. Here, by combining genetic and physiological analyses we characterize
      the AraNPQ importer and identify primary and secondary transporters of B.
      subtilis involved in the uptake of arabinosaccharides. We show that the ABC-type
      importer AraNPQ is involved in the uptake of alpha-1,5-arabinooligosaccharides,
      at least up to four L-arabinosyl units. Although this system is the key
      transporter for alpha-1,5-arabinotriose and alpha-1,5-arabinotetraose, the
      results indicate that alpha-1,5-arabinobiose also is translocated by the
      secondary transporter AraE. This broad-specificity proton symporter is the major
      transporter for arabinose and also is accountable for the uptake of xylose and
      galactose. In addition, MsmX is shown to be the ATPase that energizes the
      incomplete AraNPQ importer. Furthermore, the results suggest the existence of at
      least one more unidentified MsmX-dependent ABC importer responsible for the
      uptake of nonlinear alpha-1,2- and alpha-1,3-arabinooligosaccharides. This study
      assigns MsmX as a multipurpose B. subtilis ATPase required to energize different
      saccharide transporters, the arabinooligosaccharide-specific AraNPQ-MsmX system,
      a putative MsmX-dependent ABC transporter specific for nonlinear
      arabinooligosaccharides, and the previously characterized maltodextrin-specific
      MdxEFG-MsmX system.

PMID- 20693326
TI  - Conserved motifs involved in ATP hydrolysis by MalT, a signal transduction ATPase
      with numerous domains from Escherichia coli.
AB  - The signal transduction ATPases with numerous domains (STAND) are sophisticated
      signaling proteins that are related to AAA+ proteins and control various
      biological processes, including apoptosis, gene expression, and innate immunity.
      They function as tightly regulated switches, with the off and on positions
      corresponding to an ADP-bound, monomeric form and an ATP-bound, multimeric form,
      respectively. Protein activation is triggered by inducer binding to the sensor
      domain. ATP hydrolysis by the nucleotide-binding oligomerization domain (NOD)
      ensures the generation of the ADP-bound form. Here, we use MalT, an Escherichia
      coli transcription activator, as a model system to identify STAND conserved
      motifs involved in ATP hydrolysis besides the catalytic acidic residue. Alanine
      substitution of the conserved polar residue (H131) that is located two residues
      downstream from the catalytic residue (D129) blocks ATP hydrolysis and traps MalT
      in an active, ATP-bound, multimeric form. This polar residue is also conserved in
      AAA+. Based on AAA+ X-ray structures, we proposed that it is responsible for the
      proper positioning of the catalytic and the sensor I residues for the hydrolytic
      attack. Alanine substitution of the putative STAND sensor I (R160) abolished MalT
      activity. Substitutions of R171 impaired both ATP hydrolysis and multimerization,
      which is consistent with an arginine finger function and provides further
      evidence that ATP hydrolysis is primarily catalyzed by MalT multimers.

PMID- 20693327
TI  - Genetic analysis of the nitrogen assimilation control protein from Klebsiella
      pneumoniae.
AB  - The nitrogen assimilation control protein (NAC) from Klebsiella pneumoniae is a
      typical LysR-type transcriptional regulator (LTTR) in many ways. However, the
      lack of a physiologically relevant coeffector for NAC and the fact that NAC can
      carry out many of its functions as a dimer make NAC unusual among the LTTRs. In
      the absence of a crystal structure for NAC, we analyzed the effects of amino acid
      substitutions with a variety of phenotypes in an attempt to identify functionally
      important features of NAC. A substitution that changed the glutamine at amino
      acid 29 to alanine (Q29A) resulted in a NAC that was seriously defective in
      binding to DNA. The H26D substitution resulted in a NAC that could bind and
      repress transcription but not activate transcription. The I71A substitution
      resulted in a NAC polypeptide that remained monomeric. NAC tetramers can bind to
      both long and shorter binding sites (like other LTTRs). However, the absence of a
      coeffector to induce the conformational change needed for the switch from the
      former to the latter raised a question. Are there two conformations of NAC,
      analogous to the other LTTRs? The G217R substitution resulted in a NAC that could
      bind to the longer sites but had difficulty in binding to the shorter sites, and
      the I222R and A230R substitutions resulted in a NAC that could bind to the
      shorter sites but had difficulty in binding properly to the longer sites. Thus,
      there appear to be two conformations of NAC that can freely interconvert in the
      absence of a coeffector.

PMID- 20693328
TI  - Bright mutants of Vibrio fischeri ES114 reveal conditions and regulators that
      control bioluminescence and expression of the lux operon.
AB  - Vibrio fischeri ES114, an isolate from the Euprymna scolopes light organ,
      produces little bioluminescence in culture but is ~1,000-fold brighter when
      colonizing the host. Cell-density-dependent regulation alone cannot explain this
      phenomenon, because cells within colonies on solid medium are much dimmer than
      symbiotic cells despite their similar cell densities. To better understand this
      low luminescence in culture, we screened ~20,000 mini-Tn5 mutants of ES114 for
      increased luminescence and identified 28 independent "luminescence-up" mutants
      with insertions in 14 loci. Mutations affecting the Pst phosphate uptake system
      led to the discovery that luminescence is upregulated under low-phosphate
      conditions by PhoB, and we also found that ainS, which encodes an autoinducer
      synthase, mediates repression of luminescence during growth on plates. Other
      novel luminescence-up mutants had insertions in acnB, topA, tfoY, phoQ, guaB, and
      two specific tRNA genes. Two loci, hns and lonA, were previously described as
      repressors of bioluminescence in transgenic Escherichia coli carrying the light
      generating lux genes, and mutations in arcA and arcB were consistent with our
      report that Arc represses lux. Our results reveal a complex regulatory web
      governing luminescence and show how certain environmental conditions are
      integrated into regulation of the pheromone-dependent lux system.

PMID- 20693329
TI  - Actin-based motility of Burkholderia thailandensis requires a central acidic
      domain of BimA that recruits and activates the cellular Arp2/3 complex.
AB  - Burkholderia species use BimA for intracellular actin-based motility. Uniquely,
      Burkholderia thailandensis BimA harbors a central and acidic (CA) domain. The CA
      domain was required for actin-based motility, binding to the cellular Arp2/3
      complex, and Arp2/3-dependent polymerization of actin monomers. Our data reveal
      distinct strategies for actin-based motility among Burkholderia species.

PMID- 20693330
TI  - The caulobacter Tol-Pal complex is essential for outer membrane integrity and the
      positioning of a polar localization factor.
AB  - Cell division in Caulobacter crescentus involves constriction and fission of the
      inner membrane (IM) followed about 20 min later by fission of the outer membrane
      (OM) and daughter cell separation. In contrast to Escherichia coli, the
      Caulobacter Tol-Pal complex is essential. Cryo-electron microscopy images of the
      Caulobacter cell envelope exhibited outer membrane disruption, and cells failed
      to complete cell division in TolA, TolB, or Pal mutant strains. In wild-type
      cells, components of the Tol-Pal complex localize to the division plane in early
      predivisional cells and remain predominantly at the new pole of swarmer and
      stalked progeny upon completion of division. The Tol-Pal complex is required to
      maintain the position of the transmembrane TipN polar marker, and indirectly the
      PleC histidine kinase, at the cell pole, but it is not required for the polar
      maintenance of other transmembrane and membrane-associated polar proteins tested.
      Coimmunoprecipitation experiments show that both TolA and Pal interact directly
      or indirectly with TipN. We propose that disruption of the trans-envelope Tol-Pal
      complex releases TipN from its subcellular position. The Caulobacter Tol-Pal
      complex is thus a key component of cell envelope structure and function,
      mediating OM constriction at the final step of cell division as well as the
      positioning of a protein localization factor.

PMID- 20693332
TI  - Expression profiling of tobacco leaf trichomes identifies genes for biotic and
      abiotic stresses.
AB  - Nicotiana tabacum (tobacco) plants have short and long glandular trichomes. There
      is evidence that tobacco trichomes play several roles in the defense against
      biotic and abiotic stresses. cDNA libraries were constructed from control and
      cadmium (Cd)-treated leaf trichomes. Almost 2,000 expressed sequence tag (EST)
      cDNA clones were sequenced to analyze gene expression in control and Cd-treated
      leaf trichomes. Genes for stress response as well as for primary metabolism
      scored highly, indicating that the trichome is a biologically active and stress
      responsive tissue. Reverse transcription-PCR (RT-PCR) analysis demonstrated that
      antipathogenic T-phylloplanin-like proteins, glutathione peroxidase and several
      classes of pathogenesis-related (PR) proteins were expressed specifically or
      dominantly in trichomes. Cysteine-rich PR proteins, such as non-specific lipid
      transfer proteins (nsLTPs) and metallocarboxypeptidase inhibitors, are candidates
      for the sequestration of metals. The expression of osmotin and thaumatin-like
      proteins was induced by Cd treatment in both leaves and trichomes. Confocal laser
      scanning microscopy (CLSM) showed that glutathione levels in tip cells of both
      long and short trichomes were higher than those in other types of leaf cells,
      indicating the presence of an active sulfur-dependent protective system in
      trichomes. Our results revealed that the trichome-specific transcriptome approach
      is a powerful tool to investigate the defensive functions of trichomes against
      both abiotic and biotic stress. Trichomes are shown to be an enriched source of
      useful genes for molecular breeding towards stress-tolerant plants.

PMID- 20693331
TI  - Diversity of monomers in nonribosomal peptides: towards the prediction of origin
      and biological activity.
AB  - Nonribosomal peptides (NRPs) are molecules produced by microorganisms that have a
      broad spectrum of biological activities and pharmaceutical applications (e.g.,
      antibiotic, immunomodulating, and antitumor activities). One particularity of the
      NRPs is the biodiversity of their monomers, extending far beyond the 20
      proteogenic amino acid residues. Norine, a comprehensive database of NRPs,
      allowed us to review for the first time the main characteristics of the NRPs and
      especially their monomer biodiversity. Our analysis highlighted a significant
      similarity relationship between NRPs synthesized by bacteria and those isolated
      from metazoa, especially from sponges, supporting the hypothesis that some NRPs
      isolated from sponges are actually synthesized by symbiotic bacteria rather than
      by the sponges themselves. A comparison of peptide monomeric compositions as a
      function of biological activity showed that some monomers are specific to a class
      of activities. An analysis of the monomer compositions of peptide products
      predicted from genomic information (metagenomics and high-throughput genome
      sequencing) or of new peptides detected by mass spectrometry analysis applied to
      a culture supernatant can provide indications of the origin of a peptide and/or
      its biological activity.

PMID- 20693333
TI  - The use of cultured amphibian thyroid glands to detect thyroid hormone
      disruptors.

PMID- 20693334
TI  - Scientific impact considered.

PMID- 20693335
TI  - Scientific impact: opportunity and necessity.
AB  - Recent National Institutes of Health changes have focused attention on the
      potential scientific impact of research projects. Research with the excellent
      potential to change subsequent science or health care practice may have high
      scientific impact. Only rigorous studies that address highly significant problems
      can generate change. Studies with high impact may stimulate new research
      approaches by changing understanding of a phenomenon, informing theory
      development, or creating new research methods that allow a field of science to
      move forward. Research with high impact can transition health care to more
      effective and efficient approaches. Studies with high impact may propel new
      policy developments. Research with high scientific impact typically has both
      immediate and sustained influence on the field of study. The article includes
      ideas to articulate potential scientific impact in grant applications as well as
      possible dissemination strategies to enlarge the impact of completed projects.

PMID- 20693336
TI  - Nurses' perceptions of the organizational supports needed for the delivery of
      culturally competent care.
AB  - The purpose of this study was to determine nurses' views on the organizational
      supports needed for the delivery of culturally competent care. The research
      design was qualitative, with a case study approach. Data collection included face
      to-face interviews with 23 registered nurses, document analysis, and reports of
      critical incidents. The findings of this study revealed that caring for
      culturally diverse clients was challenging and frustrating for most participants.
      Major themes emerging from the data included language barriers, lack of training,
      difficulty with cultural differences, lack of organizational support, and
      reliance on culturally diverse staff members. Few organizational supports existed
      for delivering culturally competent care. Expectations were not explicit, and
      culturally competent care was not rewarded or supported. Recommendations for
      organizations, nursing practice, theory, and future research are made.

PMID- 20693337
TI  - Cool, but is it credible? Adolescents' and parents' approaches to genetic
      testing.
AB  - Advances in genomic science create both opportunities and challenges for future
      generations. Both adolescents and adults may benefit or be harmed by decisions
      they make in response to this new science. Using a qualitative descriptive
      design, the authors interviewed 22 adolescents (11 who were aged 14-17 years and
      11 who were 18-21 years) and 11 parents to determine levels of knowledge and
      approaches to decision making. It was found that younger adolescents and their
      parents have very limited knowledge about genetics and genetic testing. Older
      adolescents have more complete information and consider a broader range of points
      in making decisions about hypothetical situations involving genetic testing.
      Adolescents and parents need much more information to enhance their ability to
      make decisions about using genetic services. These findings have implications for
      developing interventions and public health policy highlighted by the need for
      improved education about the benefits and harms of genetic testing.

PMID- 20693338
TI  - Moderating effect of nurses' customer-oriented perception between organizational
      citizenship behaviors and satisfaction.
AB  - This study investigates whether organizational citizenship behaviors enhance job
      satisfaction among nursing personnel, while exploring whether customer-oriented
      perception has a moderating effect between nursing personnel's organizational
      citizenship behaviors and job satisfaction.The authors used a cross-sectional
      survey sent to 500 nurses with 232 valid responses. According to the research
      findings, nurses' organizational citizenship behaviors have a positive and
      significant influence on job satisfaction. Results also indicated that the
      moderating effect of nurses' customer-oriented perception on the relationship
      between their organizational citizenship behaviors and job satisfaction was
      stronger for high customer-oriented perception than it was low customer-oriented
      perception.

PMID- 20693340
TI  - Maternal depressive symptoms and parenting of children from birth to 12 years.
AB  - Maternal depression, especially in the early years of child development, affects
      parenting behaviors that have been repeatedly linked to poor outcomes in
      children. However, recurrent maternal depression may be a more potent predictor
      of parenting than depression that only occurs in the early years. Longitudinal
      population data were used to examine the influence of depression in the first 2
      years postpartum alone or in combination with recurrent episodes of depression on
      self-reported parenting behaviors known to influence children's development.
      Growth curve hierarchical linear modeling was used to examine the relationships
      among depression in the early years, recurrent depression, and parenting during
      children's first 12 years of life. Findings revealed that 63% of the depressed
      mothers reported recurrent episodes of depression. Self-reported parenting
      behaviors characterized by positive forms of discipline, firmness, and
      consistency were related to recurrent episodes of depression, whereas warmth and
      nurturant parenting behaviors were unaffected by recurrent episodes.

PMID- 20693339
TI  - Goals of fecal incontinence management identified by community-living incontinent
      adults.
AB  - The purpose of this study was to identify goals of fecal incontinence (FI)
      management and their importance to community-living adults if complete continence
      would not be possible. Participants expressed their goals of FI management in a
      semistructured interview, selected others from 12 investigator-identified goals,
      and rated their importance. Five thematic categories emerged from the 114
      participant-identified goal statements: Fecal Incontinence/Bowel Pattern,
      Lifestyle, Emotional Responses, Adverse Effects of Fecal Incontinence, and Self
      Care Practices. Participants selected a median of seven investigator-identified
      goals (range = 2 to 12). Goals selected by the most participants were decreased
      number of leaks of stool and greater confidence in controlling fecal
      incontinence. These goals also had the highest importance along with decreased
      leakage of loose or liquid stool. The type and number of management goals
      identified by participants offer a toolbox of options from which to focus therapy
      when cure is not possible and promote patient satisfaction.

PMID- 20693341
TI  - Reliability and validity of the Dementia Quality of Life measure in nursing home
      residents.
AB  - The purpose of this study was to test the reliability and validity of the
      Dementia Quality of Life (DQOL) in a sample of 486 residents from 12 nursing
      homes in the greater Baltimore area. There was some evidence of validity of the
      DQOL based on confirmatory factor analysis and Rasch model testing and criterion
      related validity. Reliability of the DQOL was somewhat supported in this study
      based on internal consistency and test-retest reliability. Alpha coefficients and
      R(2) estimations were generally low across all of the subscales. Despite these
      findings, the subscale scores remained consistent over a 12-month period. The use
      of the single-item question about QOL may not be an accurate reflection of QOL
      among nursing home residents. These findings provide additional information about
      the psychometric properties of the DQOL and offer some recommendations for
      revisions in the measure to optimally measure QOL in nursing home residents.

PMID- 20693342
TI  - Assessment of cognitive insight: a qualitative review.
AB  - The concept of cognitive insight was introduced in 2004 to describe the capacity
      of patients with psychosis to distance themselves from their psychotic
      experiences, reflect on them, and respond to corrective feedback. The Beck
      Cognitive Insight Scale (BCIS) was developed to evaluate these aspects of
      cognitive flexibility and to complement scales that describe the lack of
      awareness of mental illness and its characteristics. The BCIS has generated a
      moderate research literature, which is the subject of the current review. Several
      independent groups have demonstrated that the BCIS is reliable, demonstrates
      convergent and construct validity, and distinguishes patients with psychosis from
      healthy controls and patients without psychosis. While the majority of the
      studies have focused on the relationship of the BCIS to delusions, several have
      examined its relationship to negative symptoms, depression, anxiety, and
      functional outcome. Cognitive insight has predicted positive gains in
      psychotherapy of psychosis, and improvement in cognitive insight has been
      correlated with improvement in delusional beliefs. Finally, preliminary findings
      relate neurocognition, metacognition, and social cognition, as well as reduced
      hippocampal volume to cognitive insight. A heuristic framework is presented to
      guide future research.

PMID- 20693343
TI  - Catatonic schizophrenia: a cohort prospective study.
AB  - BACKGROUND: In the 20th century, catatonia was usually deemed a subtype of
      schizophrenia. Recently, the nature and classification of catatonia are being
      reconsidered. This study is the first to describe catatonia using prospectively
      collected data and to examine how catatonic schizophrenia differs from, or
      resembles, other types of schizophrenia. METHODS: Data were analyzed in a cohort
      of 90,079 offspring followed from birth till ages 29-41 years. Proportional
      hazards models were used, calculating time to first psychiatric hospital
      admission, to compare risk factors for catatonic schizophrenia vs "other
      schizophrenia." RESULTS: Of 568 cases of schizophrenia, 43 (7.6%) had catatonic
      schizophrenia. The sexes were equally at risk for catatonic schizophrenia in
      contrast to other schizophrenia, for which the incidence was higher in males
      (1.70, 1.42-2.03, P < .0001). Advancing paternal age had no influence on the risk
      of catatonic schizophrenia in contrast to other schizophrenia, in which the risk
      to offspring of fathers age 35+ was 1.27 (1.03-1.57, P = .03) compared with those
      of younger fathers. Those with catatonic schizophrenia were somewhat more likely
      to have older mothers (aged 35+) (relative risk = 2.14, 0.85-5.54) while maternal
      age was not related to other schizophrenia. Both were equally affected by
      parental history of schizophrenia. Patients with catatonia were significantly
      more likely to attempt suicide (P = .006). CONCLUSION: Patients with catatonic
      schizophrenia show a somewhat different profile of risk factors from those with
      other types of schizophrenia in this cohort and are more likely to attempt
      suicide. This lends some support to the hypothesis that catatonic schizophrenia
      may have a distinct etiology.

PMID- 20693344
TI  - Neutralization of interleukin-16 protects nonobese diabetic mice from autoimmune
      type 1 diabetes by a CCL4-dependent mechanism.
AB  - OBJECTIVE: The progressive infiltration of pancreatic islets by lymphocytes is
      mandatory for development of autoimmune type 1 diabetes. This inflammatory
      process is mediated by several mediators that are potential therapeutic targets
      to arrest development of type 1 diabetes. In this study, we investigate the role
      of one of these mediators, interleukin-16 (IL-16), in the pathogenesis of type 1
      diabetes in NOD mice. RESEARCH DESIGN AND METHODS: At different stages of
      progression of type 1 diabetes, we characterized IL-16 in islets using GEArray
      technology and immunoblot analysis and also quantitated IL-16 activity in cell
      migration assays. IL-16 expression was localized in islets by immunofluorescence
      and confocal imaging. In vivo neutralization studies were performed to assess the
      role of IL-16 in the pathogenesis of type 1 diabetes. RESULTS: The increased
      expression of IL-16 in islets correlated with the development of invasive
      insulitis. IL-16 immunoreactivity was found in islet infiltrating T-cells, B
      cells, NK-cells, and dendritic cells, and within an insulitic lesion, IL-16 was
      derived from infiltrating cells. CD4(+) and CD8(+) T-cells as well as B220(+) B
      cells were identified as sources of secreted IL-16. Blockade of IL-16 in vivo
      protected against type 1 diabetes by interfering with recruitment of CD4(+) T
      cells to the pancreas, and this protection required the activity of the chemokine
      CCL4. CONCLUSIONS: IL-16 production by leukocytes in islets augments the severity
      of insulitis during the onset of type 1 diabetes. IL-16 and CCL4 appear to
      function as counterregulatory proteins during disease development. Neutralization
      of IL-16 may represent a novel therapy for the prevention of type 1 diabetes.

PMID- 20693345
TI  - Liver fat content in type 2 diabetes: relationship with hepatic perfusion and
      substrate metabolism.
AB  - OBJECTIVE: Hepatic steatosis is common in type 2 diabetes. It is causally linked
      to the features of the metabolic syndrome, liver cirrhosis, and cardiovascular
      disease. Experimental data have indicated that increased liver fat may impair
      hepatic perfusion and metabolism. The aim of the current study was to assess
      hepatic parenchymal perfusion, together with glucose and fatty acid metabolism,
      in relation to hepatic triglyceride content. RESEARCH DESIGN AND METHODS: Fifty
      nine men with well controlled type 2 diabetes and 18 age-matched healthy
      normoglycemic men were studied using positron emission tomography to assess
      hepatic tissue perfusion, insulin-stimulated glucose, and fasting fatty acid
      metabolism, respectively, in relation to hepatic triglyceride content, quantified
      by proton magnetic resonance spectroscopy. Patients were divided into two groups
      with hepatic triglyceride content below (type 2 diabetes-low) or above (type 2
      diabetes-high) the median of 8.6%. RESULTS: Type 2 diabetes-high patients had the
      highest BMI and A1C and lowest whole-body insulin sensitivity (ANOVA, all P <
      0.001). Compared with control subjects and type 2 diabetes-low patients, type 2
      diabetes-high patients had the lowest hepatic parenchymal perfusion (P = 0.004)
      and insulin-stimulated hepatic glucose uptake (P = 0.013). The observed decrease
      in hepatic fatty acid influx rate constant, however, only reached borderline
      significance (P = 0.088). In type 2 diabetic patients, hepatic parenchymal
      perfusion (r = -0.360, P = 0.007) and hepatic fatty acid influx rate constant (r
      = -0.407, P = 0.007) correlated inversely with hepatic triglyceride content. In a
      pooled analysis, hepatic fat correlated with hepatic glucose uptake (r = -0.329,
      P = 0.004). CONCLUSIONS: In conclusion, type 2 diabetic patients with increased
      hepatic triglyceride content showed decreased hepatic parenchymal perfusion and
      hepatic insulin mediated glucose uptake, suggesting a potential modulating effect
      of hepatic fat on hepatic physiology.

PMID- 20693346
TI  - TNF-alpha signals through PKCzeta/NF-kappaB to alter the tight junction complex
      and increase retinal endothelial cell permeability.
AB  - OBJECTIVE: Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL
      1beta) are elevated in the vitreous of diabetic patients and in retinas of
      diabetic rats associated with increased retinal vascular permeability. However,
      the molecular mechanisms underlying retinal vascular permeability induced by
      these cytokines are poorly understood. In this study, the effects of IL-1beta and
      TNF-alpha on retinal endothelial cell permeability were compared and the
      molecular mechanisms by which TNF-alpha increases cell permeability were
      elucidated. RESEARCH DESIGN AND METHODS: Cytokine-induced retinal vascular
      permeability was measured in bovine retinal endothelial cells (BRECs) and rat
      retinas. Western blotting, quantitative real-time PCR, and immunocytochemistry
      were performed to determine tight junction protein expression and localization.
      RESULTS: IL-1beta and TNF-alpha increased BREC permeability, and TNF-alpha was
      more potent. TNF-alpha decreased the protein and mRNA content of the tight
      junction proteins ZO-1 and claudin-5 and altered the cellular localization of
      these tight junction proteins. Dexamethasone prevented TNF-alpha-induced cell
      permeability through glucocorticoid receptor transactivation and nuclear factor
      kappaB (NF-kappaB) transrepression. Preventing NF-kappaB activation with an
      inhibitor kappaB kinase (IKK) chemical inhibitor or adenoviral overexpression of
      inhibitor kappaB alpha (IkappaBalpha) reduced TNF-alpha-stimulated permeability.
      Finally, inhibiting protein kinase C zeta (PKCzeta) using both a peptide and a
      novel chemical inhibitor reduced NF-kappaB activation and completely prevented
      the alterations in the tight junction complex and cell permeability induced by
      TNF-alpha in cell culture and rat retinas. CONCLUSIONS: These results suggest
      that PKCzeta may provide a specific therapeutic target for the prevention of
      vascular permeability in retinal diseases characterized by elevated TNF-alpha,
      including diabetic retinopathy.

PMID- 20693347
TI  - AMP-activated protein kinase alpha2 subunit is required for the preservation of
      hepatic insulin sensitivity by n-3 polyunsaturated fatty acids.
AB  - OBJECTIVE: The induction of obesity, dyslipidemia, and insulin resistance by high
      fat diet in rodents can be prevented by n-3 long-chain polyunsaturated fatty
      acids (LC-PUFAs). We tested a hypothesis whether AMP-activated protein kinase
      (AMPK) has a role in the beneficial effects of n-3 LC-PUFAs. RESEARCH DESIGN AND
      METHODS: Mice with a whole-body deletion of the alpha2 catalytic subunit of AMPK
      (AMPKalpha2(-/-)) and their wild-type littermates were fed on either a low-fat
      chow, or a corn oil-based high-fat diet (cHF), or a cHF diet with 15% lipids
      replaced by n-3 LC-PUFA concentrate (cHF+F). RESULTS: Feeding a cHF diet induced
      obesity, dyslipidemia, hepatic steatosis, and whole-body insulin resistance in
      mice of both genotypes. Although cHF+F feeding increased hepatic AMPKalpha2
      activity, the body weight gain, dyslipidemia, and the accumulation of hepatic
      triglycerides were prevented by the cHF+F diet to a similar degree in both
      AMPKalpha2(-/-) and wild-type mice in ad libitum-fed state. However, preservation
      of hepatic insulin sensitivity by n-3 LC-PUFAs required functional AMPKalpha2 and
      correlated with the induction of adiponectin and reduction in liver
      diacylglycerol content. Under hyperinsulinemic-euglycemic conditions, AMPKalpha2
      was essential for preserving low levels of both hepatic and plasma triglycerides,
      as well as plasma free fatty acids, in response to the n-3 LC-PUFA treatment.
      CONCLUSIONS: Our results show that n-3 LC-PUFAs prevent hepatic insulin
      resistance in an AMPKalpha2-dependent manner and support the role of adiponectin
      and hepatic diacylglycerols in the regulation of insulin sensitivity. AMPKalpha2
      is also essential for hypolipidemic and antisteatotic effects of n-3 LC-PUFA
      under insulin-stimulated conditions.

PMID- 20693348
TI  - Sugar-sweetened beverages and risk of metabolic syndrome and type 2 diabetes: a
      meta-analysis.
AB  - OBJECTIVE: Consumption of sugar-sweetened beverages (SSBs), which include soft
      drinks, fruit drinks, iced tea, and energy and vitamin water drinks has risen
      across the globe. Regular consumption of SSBs has been associated with weight
      gain and risk of overweight and obesity, but the role of SSBs in the development
      of related chronic metabolic diseases, such as metabolic syndrome and type 2
      diabetes, has not been quantitatively reviewed. RESEARCH DESIGN AND METHODS: We
      searched the MEDLINE database up to May 2010 for prospective cohort studies of
      SSB intake and risk of metabolic syndrome and type 2 diabetes. We identified 11
      studies (three for metabolic syndrome and eight for type 2 diabetes) for
      inclusion in a random-effects meta-analysis comparing SSB intake in the highest
      to lowest quantiles in relation to risk of metabolic syndrome and type 2
      diabetes. RESULTS: Based on data from these studies, including 310,819
      participants and 15,043 cases of type 2 diabetes, individuals in the highest
      quantile of SSB intake (most often 1-2 servings/day) had a 26% greater risk of
      developing type 2 diabetes than those in the lowest quantile (none or <1
      serving/month) (relative risk [RR] 1.26 [95% CI 1.12-1.41]). Among studies
      evaluating metabolic syndrome, including 19,431 participants and 5,803 cases, the
      pooled RR was 1.20 [1.02-1.42]. CONCLUSIONS: In addition to weight gain, higher
      consumption of SSBs is associated with development of metabolic syndrome and type
      2 diabetes. These data provide empirical evidence that intake of SSBs should be
      limited to reduce obesity-related risk of chronic metabolic diseases.

PMID- 20693349
TI  - Mannose-binding lectin genotype and phenotype in patients with type 2 diabetes
      and myocardial infarction: a report from the DIGAMI 2 trial.
AB  - OBJECTIVE: The present study characterizes mannose-binding lectin (MBL), an
      activator of the complement system and thereby important for inflammatory
      activation, in patients with diabetes and myocardial infarction. RESEARCH DESIGN
      AND METHODS: Serum (S)-MBL was determined at hospital admission in 387 patients
      with type 2 diabetes (median age 70 years; 68% male) with myocardial infarction,
      and genotyping was performed in 287 patients. Cardiovascular events
      (cardiovascular mortality and nonfatal myocardial infarction or stroke) were
      recorded during 2.5 years. RESULTS: Median S-MBL was 1,212 MUg/l (interquartile
      range [IQR] 346-2,681 MUg/l). Of the subjects, 54% in the geno- and phenotype
      subgroup had a high-coding MBL genotype (median S-MBL=2,658 MUg/l [IQR 1,715
      3,829]) and 46% a low-coding MBL genotype (373 MUg/l [100-765]). S-MBL did not
      correlate with age, BMI, creatinine clearance, glucose, or A1C. Cardiovascular
      events occurred in 136 (35%) patients. S-MBL did not predict events in
      univariable analyses (hazard ratio 0.93 [95% CI 0.85-1.01]; P=0.09). In
      unadjusted analyses, the risk of events was lower in patients with a high
      genotype and S-MBL above the median for their genotype (0.49 [0.26-0.92];
      P=0.026) than for patients with a low genotype and S-MBL below the median for
      their genotype. The prediction capacity of the geno- and phenotype model was of
      borderline significance in adjusted Cox regression. CONCLUSIONS: Patients with
      type 2 diabetes and myocardial infarction have MBL genotypes that are similar to
      those known in the general population. The combination of a low-coding MBL
      genotype with a low S-MBL appears to be prognostically unfavorable, but the
      association is blunted by traditional risk markers.

PMID- 20693350
TI  - Effect of intrauterine diabetes exposure on the incidence of end-stage renal
      disease in young adults with type 2 diabetes.
AB  - OBJECTIVE: We examined the effect of intrauterine diabetes exposure (IDE) on the
      incidence of diabetic end-stage renal disease (ESRD) in Pima Indians with type 2
      diabetes. RESEARCH DESIGN AND METHODS: Individuals were followed from their first
      diabetic examination until December 2006, death, ESRD, or age of 45 years.
      RESULTS: Among the 1,850 diabetic participants, 102 had IDE. ESRD developed in
      57, 5 of whom had IDE. Cumulative incidence of ESRD by age 45 was 19.3% in
      participants with IDE and 5.1% in those without; the age- and sex-adjusted
      incidence rate ratio was 4.12 (95% CI 1.54-11.02). After additional adjustment
      for age at diabetes onset, ESRD incidence was similar in the two groups
      (incidence rate ratio 1.38, 95% CI 0.45-4.24). CONCLUSIONS: IDE increases the age
      and sex-adjusted incidence of ESRD fourfold in young adults with type 2
      diabetes, mediated primarily by the earlier onset of type 2 diabetes in those
      with IDE.

PMID- 20693351
TI  - Pulsatile stress in middle-aged patients with type 1 or type 2 diabetes compared
      with nondiabetic control subjects.
AB  - OBJECTIVE: Arterial pulse pressure is considered to be an independent
      cardiovascular risk factor. We compared pulse pressure during an active
      orthostatic test in middle-aged patients with type 1 diabetes and with type 2
      diabetes and corresponding nondiabetic control subjects. RESEARCH DESIGN AND
      METHODS: Forty patients with type 1 diabetes (mean age 50 years, diabetes
      duration 23 years, and BMI 23.0 kg/m2) were compared with 40 nonhypertensive
      patients with type 2 diabetes (respectively, 50 years, 8 years, and 29.7 kg/m2).
      Patients taking antihypertensive agents or with renal insufficiency were
      excluded. All patients were evaluated with a continuous noninvasive arterial
      blood pressure monitoring (Finapres) in standing (1 min), squatting (1 min), and
      again standing position (1 min). Patients with type 1 or type 2 diabetes were
      compared with two groups of 40 age-, sex- and BMI-matched healthy subjects.
      RESULTS: Patients with type 1 diabetes and patients with type 2 diabetes showed
      significantly higher pulse pressure, heart rate, and double product of pulse
      pressure and heart rate (PP*HR) (type 1: 5,263 vs. 4,121 mmHg/min, P=0.0004; type
      2: 5,359 vs. 4,321 mmHg, P=0.0023) levels than corresponding control subjects.
      There were no significant differences between patients with type 1 diabetes and
      type 2 diabetes regarding pulse pressure (59 vs. 58 mmHg), heart rate (89 vs.
      88/min), and PP*HR (5,263 vs. 5,359 mmHg/min). CONCLUSIONS: Patients with type 1
      diabetes have increased levels of peripheral PP, an indirect marker of arterial
      stiffness, and PP*HR, an index of pulsatile stress, comparable to those of
      nonhypertensive patients with type 2 diabetes at similar mean age of 50 years.

PMID- 20693353
TI  - Impact of baseline renal function on the efficacy and safety of aliskiren added
      to losartan in patients with type 2 diabetes and nephropathy.
AB  - OBJECTIVE: Proteinuric diabetic patients with reduced glomerular filtration rate
      (GFR) are at high risk of renal and cardiovascular disease progression and
      treatment-related adverse events. This post hoc analysis assessed the efficacy
      and safety of aliskiren added to the maximal recommended dose of losartan
      according to baseline estimated GFR (eGFR) (stage 1-3 chronic kidney disease
      [CKD]). RESEARCH DESIGN AND METHODS: In the Aliskiren in the Evaluation of
      Proteinuria in Diabetes (AVOID) study, 599 hypertensive patients with type 2
      diabetes and nephropathy received 6 months of aliskiren (150 mg daily titrated to
      300 mg daily after 3 months) or placebo added to 100 mg losartan and optimal
      antihypertensive therapy. Exclusion criteria included eGFR<30 ml/min per 1.73 m2
      and serum potassium>5.1 mmol/l. RESULTS: Baseline characteristics were similar
      between treatment groups in all CKD stages. The antiproteinuric effects of
      aliskiren were consistent across CKD stages (19, 22, and 18% reduction). In the
      stage 3 CKD group, baseline serum creatinine levels were equal, but renal
      dysfunction, prespecified as a postrandomization serum creatinine elevation>176.8
      MUmol/l (2.0 mg/dl) occurred more frequently in the placebo group (29.2 vs.
      13.6%, P=0.032). Serum potassium elevations>5.5 mmol/l (based on a single
      measurement) were more frequent with aliskiren (22.5 vs. 13.6%) in stage 3 CKD.
      Adverse event rates were similar between treatments, irrespective of CKD stage.
      CONCLUSIONS: Aliskiren added to losartan reduced albuminuria and renal
      dysfunction and was well tolerated, except for hyperkalemia (stage 3),
      independent of baseline CKD stage in patients with type 2 diabetes, hypertension,
      and nephropathy.

PMID- 20693354
TI  - Premeal injection of rapid-acting insulin reduces postprandial glycemic
      excursions in type 1 diabetes.
AB  - OBJECTIVE: To assess the effect of three premeal timings of rapid-acting insulin
      on postprandial glucose excursions in type 1 diabetes. RESEARCH DESIGN AND
      METHODS: Ten subjects participated in a three-way randomized crossover trial.
      Mean +/- SD age was 45.5 +/- 12.1 years, A1C was 8.55 +/- 1.50%, duration of
      diabetes was 23.8 +/- 7.8 years, and duration of continuous subcutaneous insulin
      infusion therapy was 8.5 +/- 6.1 years. Insulin aspart was administered at 30,
      15, or 0 min before mealtime. RESULTS: Area under the curve was lower in the -15
      stratum (0.41 +/- 0.51 mmol/l/min) than that in the -30 stratum (1.89 +/- 0.72
      mmol/l/min, P = 0.029) and 0 stratum (2.11 +/- 0.66 mmol/l/min, P = 0.030).
      Maximum glucose excursion was lower in the -15 stratum (4.77 +/- 0.52 mmol/l)
      than that in the -30 (6.48 +/- 0.76 mmol/l, P = 0.025) and 0 stratum (6.93 +/-
      0.76 mmol/l, P = 0.022). Peak glucose level was lower in the -15 stratum (9.26 +/
      0.72 mmol/l) than that in the -30 stratum (11.74 +/- 0.80 mmol/l, P = 0.007) and
      the 0 stratum (12.29 +/- 0.93, P = 0.009). Time spent in the 3.5-10 mmol/l range
      was higher in the -15 stratum (224.5 +/- 25.0 min) than that in the 0 stratum
      (90.5 +/- 23.2 min, P = 0.001). There was no significant difference in occurrence
      of glucose levels <3.5 mmol/l between strata (P = 0.901). CONCLUSIONS:
      Administration of rapid-acting insulin analogs 15 min before mealtime results in
      lower postprandial glucose excursions and more time spent in the 3.5-10.0 mmol/l
      range, without increased risk of hypoglycemia.

PMID- 20693355
TI  - Setaria viridis: a model for C4 photosynthesis.
AB  - C(4) photosynthesis drives productivity in several major food crops and bioenergy
      grasses, including maize (Zea mays), sugarcane (Saccharum officinarum), sorghum
      (Sorghum bicolor), Miscanthus x giganteus, and switchgrass (Panicum virgatum).
      Gains in productivity associated with C(4) photosynthesis include improved water
      and nitrogen use efficiencies. Thus, engineering C(4) traits into C(3) crops is
      an attractive target for crop improvement. However, the lack of a small, rapid
      cycling genetic model system to study C(4) photosynthesis has limited progress in
      dissecting the regulatory networks underlying the C(4) syndrome. Setaria viridis
      is a member of the Panicoideae clade and is a close relative of several major
      feed, fuel, and bioenergy grasses. It is a true diploid with a relatively small
      genome of ~510 Mb. Its short stature, simple growth requirements, and rapid life
      cycle will greatly facilitate genetic studies of the C(4) grasses. Importantly,
      S. viridis uses an NADP-malic enzyme subtype C(4) photosynthetic system to fix
      carbon and therefore is a potentially powerful model system for dissecting C(4)
      photosynthesis. Here, we summarize some of the recent advances that promise
      greatly to accelerate the use of S. viridis as a genetic system. These include
      our recent successful efforts at regenerating plants from seed callus,
      establishing a transient transformation system, and developing stable
      transformation.

PMID- 20693356
TI  - Functional differentiation of the glycosyltransferases that contribute to the
      chemical diversity of bioactive flavonol glycosides in grapevines (Vitis
      vinifera).
AB  - We identified two glycosyltransferases that contribute to the structural
      diversification of flavonol glycosides in grapevine (Vitis vinifera):
      glycosyltransferase 5 (Vv GT5) and Vv GT6. Biochemical analyses showed that Vv
      GT5 is a UDP-glucuronic acid:flavonol-3-O-glucuronosyltransferase (GAT), and Vv
      GT6 is a bifunctional UDP-glucose/UDP-galactose:flavonol-3-O
      glucosyltransferase/galactosyltransferase. The Vv GT5 and Vv GT6 genes have very
      high sequence similarity (91%) and are located in tandem on chromosome 11,
      suggesting that one of these genes arose from the other by gene duplication. Both
      of these enzymes were expressed in accordance with flavonol synthase gene
      expression and flavonoid distribution patterns in this plant, corroborating their
      significance in flavonol glycoside biosynthesis. The determinant of the
      specificity of Vv GT5 for UDP-glucuronic acid was found to be Arg-140, which
      corresponded to none of the determinants previously identified for other plant
      GATs in primary structures, providing another example of convergent evolution of
      plant GAT. We also analyzed the determinants of the sugar donor specificity of Vv
      GT6. Gln-373 and Pro-19 were found to play important roles in the bifunctional
      specificity of the enzyme. The results presented here suggest that the sugar
      donor specificities of these Vv GTs could be determined by a limited number of
      amino acid substitutions in the primary structures of protein duplicates,
      illustrating the plasticity of plant glycosyltransferases in acquiring new sugar
      donor specificities.

PMID- 20693357
TI  - Streptomyces sanyensis sp. nov., isolated from mangrove sediment.
AB  - A novel strain, 219820(T), whose metabolites were found to be active against
      tumour cells, was isolated and characterized. The isolate belonged to the genus
      Streptomyces and had white to grey aerial mycelium and long chains of smooth
      spores in the aerial mycelium. A phylogenetic tree based on 16S rRNA gene
      sequences showed that strain 219820(T) had highest similarity to members of the
      genus Streptomyces and was most closely, albeit loosely, associated with
      Streptomyces crystallinus NBRC 15401(T) (98.624 % similarity), Streptomyces
      melanogenes NBRC 12890(T) (98.565 %) and Streptomyces noboritoensis NBRC 13065(T)
      (98.564 %). However, DNA-DNA relatedness and phenotypic data readily
      distinguished strain 219820(T) from these phylogenetically related type strains.
      It is evident from the combination of genotypic and phenotypic data that strain
      219820(T) represents a novel species of the genus Streptomyces, for which the
      name Streptomyces sanyensis sp. nov. is proposed; the type strain is 219820(T) (
      = CGMCC 4.5626(T)  = DSM 42014(T)).

PMID- 20693352
TI  - Interactions of dietary whole-grain intake with fasting glucose- and insulin
      related genetic loci in individuals of European descent: a meta-analysis of 14
      cohort studies.
AB  - OBJECTIVE: Whole-grain foods are touted for multiple health benefits, including
      enhancing insulin sensitivity and reducing type 2 diabetes risk. Recent genome
      wide association studies (GWAS) have identified several single nucleotide
      polymorphisms (SNPs) associated with fasting glucose and insulin concentrations
      in individuals free of diabetes. We tested the hypothesis that whole-grain food
      intake and genetic variation interact to influence concentrations of fasting
      glucose and insulin. RESEARCH DESIGN AND METHODS: Via meta-analysis of data from
      14 cohorts comprising ~ 48,000 participants of European descent, we studied
      interactions of whole-grain intake with loci previously associated in GWAS with
      fasting glucose (16 loci) and/or insulin (2 loci) concentrations. For tests of
      interaction, we considered a P value <0.0028 (0.05 of 18 tests) as statistically
      significant. RESULTS: Greater whole-grain food intake was associated with lower
      fasting glucose and insulin concentrations independent of demographics, other
      dietary and lifestyle factors, and BMI (beta [95% CI] per 1-serving-greater whole
      grain intake: -0.009 mmol/l glucose [-0.013 to -0.005], P < 0.0001 and -0.011
      pmol/l [ln] insulin [-0.015 to -0.007], P = 0.0003). No interactions met our
      multiple testing-adjusted statistical significance threshold. The strongest SNP
      interaction with whole-grain intake was rs780094 (GCKR) for fasting insulin (P =
      0.006), where greater whole-grain intake was associated with a smaller reduction
      in fasting insulin concentrations in those with the insulin-raising allele.
      CONCLUSIONS: Our results support the favorable association of whole-grain intake
      with fasting glucose and insulin and suggest a potential interaction between
      variation in GCKR and whole-grain intake in influencing fasting insulin
      concentrations.

PMID- 20693358
TI  - Thermosipho globiformans sp. nov., an anaerobic thermophilic bacterium that
      transforms into multicellular spheroids with a defect in peptidoglycan formation.
AB  - An anaerobic rod-shaped thermophile was isolated from a hydrothermal vent at
      Suiyo Seamount, Izu-Bonin Arc, western Pacific Ocean, and was named strain
      MN14(T). The rods were gram-negative-staining, non-motile without flagella, 2-4
      um long and 0.5 um wide, and divided by binary fission in the mid-exponential
      phase. The cells were surrounded by a sheath-like structure (toga) and occurred
      singly or in chains. Spheroids containing multiple cells were observed not only
      in the stationary phase, as previously observed for species of the order
      Thermotogales, but also from the early exponential phase. Transmission electron
      microscopy revealed that the peptidoglycan in rods partly disintegrated in the
      early growth phases and that the outer membrane of the spheroids was not
      completely lined with peptidoglycan. These findings suggested that the spheroids
      were formed from rods by the disintegration of peptidoglycan and subsequent
      inflation of the outer membrane. The spheroids eventually generated tiny cells in
      the periplasmic space, indicating a viviparous mode of proliferation in addition
      to binary fission. Strain MN14(T) grew at 40-75  degrees C, pH 5.0-8.2 and with
      0.25-5.20 % (w/v) NaCl, with optimal growth occurring at 68  degrees C, pH 6.8
      and with 2.5 % NaCl. The shortest doubling time was 24 min, assuming that the
      strain propagated only by binary fission. Elemental sulfur enhanced growth, but
      was not essential. Thiosulfate was not an electron acceptor for growth. The
      strain was a chemo-organotroph that grew on yeast extract as the sole growth
      substrate. Tryptone and starch supported its growth in the presence of yeast
      extract. The G+C content of the genomic DNA was 31.7 mol%. Phylogenetic analysis
      based on the 16S rRNA gene sequence indicated that this strain belonged to the
      genus Thermosipho. No significant DNA-DNA hybridization was observed between the
      genomic DNA of strain MN14(T) and phylogenetically related species of the genus
      Thermosipho. Based on this evidence, strain MN14(T) is proposed to represent a
      novel species, named Thermosipho globiformans sp. nov. The species epithet
      globiformans reflects the formation of multicellular and reproductive spheroids
      by the novel strain. The type strain of this species is MN14(T) ( = JCM 15059(T)
      = DSM 19918(T)).

PMID- 20693359
TI  - Halolamina pelagica gen. nov., sp. nov., a new member of the family
      Halobacteriaceae.
AB  - Two extremely halophilic archaeal strains, TBN21(T) and TBN49, were isolated from
      the Taibei marine solar saltern near Lianyungang city, Jiangsu province, China.
      Cells of the two strains were pleomorphic and gram-negative and colonies were
      red. Strains TBN21(T) and TBN49 were able to grow at 25-50  degrees C (optimum 37
      degrees C), at 1.4-5.1 M NaCl (optimum 3.4-3.9 M) and at pH 5.5-9.5 (optimum pH
      7.0-7.5) and neither strain required Mg(2+) for growth. Cells lysed in distilled
      water and the minimal NaCl concentration to prevent cell lysis was 8 % (w/v). The
      major polar lipids of the two strains were phosphatidic acid,
      phosphatidylglycerol, phosphatidylglycerol phosphate methyl ester,
      phosphatidylglycerol sulfate and eight glycolipids; three of these glycolipids
      (GL3, GL4 and GL5) were chromatographically identical to sulfated mannosyl
      glucosyl diether (S-DGD-1), galactosyl mannosyl glucosyl diether (TGD-1) and
      mannosyl glucosyl diether (DGD-1), respectively. Phylogenetic analysis revealed
      that strains TBN21(T) and TBN49 formed a distinct clade with their closest
      relative, Halobaculum gomorrense JCM 9908(T) (89.0-89.5 % 16S rRNA gene sequence
      similarity). The DNA G+C contents of strains TBN21(T) and TBN49 were 64.8 and
      62.7 mol%, respectively. DNA-DNA hybridization between strains TBN21(T) and TBN49
      was 90.1 %. The phenotypic, chemotaxonomic and phylogenetic properties suggest
      that strains TBN21(T) and TBN49 represent a novel species in a new genus within
      the family Halobacteriaceae, for which the name Halolamina pelagica gen. nov.,
      sp. nov. is proposed. The type strain of Halolamina pelagica is TBN21(T) ( =
      CGMCC 1.10329(T)  = JCM 16809(T)).

PMID- 20693360
TI  - Marmoricola korecus sp. nov.
AB  - A novel actinomycete, designated strain Sco-A36(T), was isolated from volcanic
      ash. Cells were aerobic, Gram-stain-positive, oxidase-negative, catalase
      positive, non-motile cocci; colonies were yellow-coloured, smooth, entire and
      convex. Phylogenetic analysis showed that the organism formed a distinct phyletic
      line within the radiation of the genus Marmoricola. Its closest phylogenetic
      neighbours were Marmoricola aurantiacus DSM 12652(T) (97.9 % 16S rRNA gene
      sequence similarity), Marmoricola scoriae Sco-D01(T) (97.9 %), Marmoricola
      aequoreus SST-45(T) (97.4 %) and Marmoricola bigeumensis MSL-05(T) (96.3 %). The
      diagnostic diamino acid in the cell walls was ll-diaminopimelic acid. The
      predominant menaquinone was MK-8(H(4)). The polar lipids contained
      phosphatidylinositol, diphosphatidylglycerol, phosphatidylglycerol,
      phosphatidylcholine and an unknown phospholipid. The predominant fatty acids were
      C(16 : 0), C(17 : 1)omega8c, C(18 : 1)omega9c and C(16 : 1)omega7c and/or iso
      C(15 : 0) 2-OH. The DNA G+C content of strain Sco-A36(T) was 71.0 mol%. Levels of
      DNA-DNA relatedness between the new isolate and the type strains of recognized
      species of the genus Marmoricola were 4.9-29.2 %. The phenotypic and DNA-DNA
      hybridization data presented here strongly suggest that strain Sco-A36(T)
      represents a novel species of the genus Marmoricola, for which the name
      Marmoricola korecus sp. nov. is proposed. The type strain is Sco-A36(T) ( = KCTC
      19596(T) = DSM 22128(T)).

PMID- 20693361
TI  - Streptomyces sparsus sp. nov., isolated from a saline and alkaline soil.
AB  - A salt- and alkali-tolerant actinomycete strain, YIM 90018(T), was isolated from
      a saline and alkaline soil sample collected from Qinghai, China. Aerial hyphae of
      strain YIM 90018(T) were only produced on YIM 82 agar. Vegetative hyphae were
      well developed and did not fragment. Straight or flexuous (rectiflexibiles) spore
      chains were produced. The isolate grew well with 25 % (w/v) MgCl(2)  x  6H(2)O
      and at pH 10. All of these characters indicated that strain YIM 90018(T) belonged
      to the genus Streptomyces. On the basis of phylogenetic analysis of the 16S rRNA
      gene sequence, DNA-DNA hybridization and phenotypic characteristics, strain YIM
      90018(T) could be differentiated from all recognized species of the genus
      Streptomyces. A novel species, Streptomyces sparsus sp. nov., is proposed, with
      strain YIM 90018(T) ( = CCTCC AA204019(T) = DSM 41858(T)) as the type strain.

PMID- 20693363
TI  - Halomonas daqiaonensis sp. nov., a moderately halophilic, denitrifying bacterium
      isolated from a littoral saltern.
AB  - Two novel gram-negative, oxidase- and catalase-positive, rod-shaped bacterial
      strains, designated YCSA28(T) and YCSA39, were isolated from sediment of Daqiao
      saltern, Jimo, Qingdao, on the east coast of China. The two strains grew
      optimally at 28-30  degrees C, at pH 7.5 and in the presence of 7-8 % (w/v) NaCl.
      They were assigned to the genus Halomonas, class Gammaproteobacteria, based on
      16S rRNA gene sequence analysis. The major cellular fatty acids of the two
      strains were C(18 : 1)omega7c (42.9 %), C(16 : 0) (23.1 %) and C(16 :
      1)omega7c/omega6c (18.0 %), and Q-9 was the major ubiquinone. The G+C content of
      the DNA of strains YCSA28(T) and YCSA39 was 63.7 and 63.9 mol%, respectively. The
      predominant respiratory lipoquinone, cellular fatty acid profiles and DNA G+C
      content of strains YCSA28(T) and YCSA39 were consistent with those of recognized
      species of the genus Halomonas. Levels of DNA-DNA relatedness between strains
      YCSA28(T) and YCSA39, between YCSA28(T) and Halomonas ventosae Al12(T), and
      between YCSA39 and H. ventosae Al12(T) were 95, 45 and 50 %, respectively.
      Together, these data indicated that strains YCSA28(T) and YCSA39 represent a
      single novel species of the genus Halomonas, for which the name Halomonas
      daqiaonensis sp. nov. is proposed. The type strain is YCSA28(T) ( = CGMCC
      1.9150(T)  = NCCB 100305(T)  = MCCC 1B00920(T)).

PMID- 20693362
TI  - Mycobacterium europaeum sp. nov., a scotochromogenic species related to the
      Mycobacterium simiae complex.
AB  - Four strains isolated in the last 15 years were revealed to be identical in their
      16S rRNA gene sequences to MCRO19, the sequence of which was deposited in GenBank
      in 1995. In a polyphasic analysis including phenotypic and genotypic features,
      the five strains (including MCRO19), which had been isolated in four European
      countries, turned out to represent a unique taxonomic entity. They are
      scotochromogenic slow growers and are genetically related to the group that
      included Mycobacterium simiae and 15 other species. The novel species
      Mycobacterium europaeum sp. nov. is proposed to accommodate these five strains.
      Strain FI-95228(T) ( = DSM 45397(T)  = CCUG 58464(T)) was chosen as the type
      strain. In addition, a thorough revision of the phenotypic and genotypic
      characters of the species related to M. simiae was conducted which leads us to
      suggest the denomination of the 'Mycobacterium simiae complex' for this group.

PMID- 20693364
TI  - Flavobacterium banpakuense sp. nov., isolated from leaf-and-branch compost.
AB  - A strictly aerobic, Gram-stain-negative, yellow-pigmented, non-spore-forming,
      motile (by gliding), rod-shaped bacterium, designated strain 15F3(T), was
      isolated from leaf-and-branch compost. Phylogenetic analysis based on 16S rRNA
      gene sequences showed that strain 15F3(T) was most closely related to
      Flavobacterium reichenbachii WB 3.2-61(T) and formed a distinct phyletic lineage
      within the genus Flavobacterium, the type genus of the family Flavobacteriaceae.
      Growth was observed at 10-34  degrees C (optimum, 30  degrees C) and pH 6.0-8.0
      (optimum, pH 7.0). No growth occurred in the presence of >=2 % (w/v) NaCl. Strain
      15F3(T) reduced nitrate to nitrogen and showed catalase activity but no oxidase
      activity. The predominant cellular fatty acids were iso-C(15 : 0) and summed
      feature 3 (comprising C(16 : 1)omega7c and/or iso-C(15 : 0) 2-OH). The major
      isoprenoid quinone was menaquinone-6. The G+C content of the genomic DNA was 31.1
      mol%. On the basis of data from this polyphasic study, strain 15F3(T) may be
      classified as a representative of a novel species within the genus
      Flavobacterium, for which the name Flavobacterium banpakuense sp. nov. is
      proposed; the type strain is 15F3(T) ( = KACC 14225(T)  = JCM 16466(T)).

PMID- 20693365
TI  - Rheotaxis and chemoreception in the freshwater snail biomphalaria glabrata (say):
      estimation of the molecular weights of active factors.
AB  - 1. Dilute solutions of lettuce and wheatgerm extracts trigger positive rheotaxis
      in the freshwater snail, Biomphalaria glabrata. This response can be used as the
      basis of a sensitive bioassay for characterizing and identifying the chemicals to
      which the snail is attracted. 2. Using ultrafiltration techniques a range of
      different molecular weight fractions could be attenuated or removed from these
      extracts. By comparing the activity of these solutions with that of the original
      extract an estimate of the molecular weight of the attractant could be made. 3.
      In both cases the molecular weights of the attractants were estimated as being
      greater than 1000. Those in the lettuce were estimated at lying between 1000 and
      10,000; whereas for wheatgerm the values were slightly higher and lay between
      10,000 and 40,000. The ecological significance of these results is discussed.

PMID- 20693366
TI  - Acid phosphatase during the life cycle of the nematode, panagrellus silusiae.
AB  - This study showed that there is a relationship between acid phosphatase levels
      and life cycle stages in the nematode, Panagrellus silusiae. Ten different
      isozymes of acid phosphatase were separated electrophoretically. Relative
      activity peaked at different stages in the life cycle for the different isozymes.
      Later in the life cycle, there is a general decrease in the relative activity of
      acid phosphatase itself, while there is a concurrent increase in the number of
      isozymes present. At least 97% of the acid phosphatase in P. silusiac is soluble
      (unbound). Acid phosphatase appears to be present in large quantities in the
      entire gastrointestinal tract, the excretory canals, and the reproductive system
      of mature Panagrellus silusiae.

PMID- 20693367
TI  - Morphology of the mouthparts of larval lobsters, homarus americanus (decapoda:
      nephropidae), with special emphasis on their setae.
AB  - 1. This study provides a detailed account of the morphology of the mouthparts of
      larval lobsters (Homarus americanus) and the setae they bear. The results
      describe the types of setae found on the mouthparts, present a scheme for their
      classification, describe the distribution of the various setal types, and present
      observations of interesting or previously overlooked features of the mouthparts
      themselves. 2. A scheme of classification (based on the external morphology of
      the setae, particularly the nature and distribution of the setules) has been
      devised to describe and categorize the types of setae found on the mouthparts.
      The setal complement may be arranged into ten major categories, in some of which
      the variation is sufficient to warrant subdivision into several types of setae.
      3. Detailed descriptions of the mouthparts and the distribution of their setae
      are presented and major developmental trends are noted. Changes in the mouthparts
      which occur as lobsters pass through the first four stages generally include
      increases in the size of mouthparts and in the number of setae they bear. Of
      special interest is the transformation of the comparatively delicate teeth of the
      first-stage mandible into the massive molars of the fourth stage. The coordinated
      development of teeth on the gnathal lobe of the mandible and on the ischium of
      the third maxilliped emphasizes the coordinated manner in which these appendages
      function. It is evident that the development of the mandibles and third
      maxillipeds enables lobsters to deal successfully with the more substantial food
      they encounter in the benthic environment, which they usually enter at the fourth
      or fifth stage. 4. The various functions and possible functions (for example,
      chemosensory, tactile, and mechanical) of the setae borne on the mouthparts are
      discussed in light of the available functional and physiological evidence. The
      possibility of filter feeding in lobsters, particularly in the constantly
      swimming, planktonic larval forms, is considered.

PMID- 20693368
TI  - Osmotic and ionic regulation in several Western atlantic callianassidae
      (crustacea, decapoda, thalassinidea).
AB  - Osmotic and ionic regulatory capacities of callianassid mud shrimps, Callianassa
      jamaicense, C. major, and C. islagrande, are correlated to their distributions on
      the Louisiana coast. Callianassa jamaicense burrows in muddy estuaries where
      salinity may commonly fall to < 5 per thousand, but C. major and C. islagrande
      usually burrow in sandy beaches bathed by higher salinities. Lower lethal limits
      of salinity are < 2 per thousand for C. jamaicense, 7-8 per thousand for C. major
      and probably just below 15 per thousand for adult C. islagrande. After exposure
      to low salinity C. jamaicense exhibits better volume control than the other two
      species. Blood osmotic, sodium, and chloride concentrations in C. jamaicense are
      regulated near stable levels at acclimation salinities beneath approximately 20
      per thousand but those of C. major and C. islagrande are not. Blood magnesium is
      slightly hyper-regulated by C. jamaicense at most acclimation salinities < 25 per
      thousand and more markedly hyper-regulated at salinities < 10 per thousand; it is
      also slightly hyper-regulated by C. major at acclimation salinities < 30 per
      thousand. After direct transfer of C. jamaicense from 20 per thousand salinity to
      3 per thousand salinity, blood osmotic, sodium, and chloride concentrations fall
      slightly but approach stable concentrations within 12 hours; blood magnesium
      concentration falls less rapidly. When C. jamaicense is transferred from 20 to 37
      per thousand, blood osmotic, sodium, and chloride concentrations increase
      markedly during the first day and continue to slowly increase through day 9;
      blood magnesium increases to a near stable level by day 4. Differences in
      osmoregulatory capacities, along with substrate preferences, appear to limit
      distributions of Callianassidae on the Louisiana coast. With one exception,
      previous studies suggest that osmoregulatory ability does not occur in this
      group. The present report of osmoregulatory ability in C. jamaicense documents a
      second exception.

PMID- 20693369
TI  - Larval rearing, metamorphosis, growth and reproduction of the eolid nudibranch
      hermissenda crassicornis (eschscholtz, 1831) (gastropoda: opisthobranchia).
AB  - 1. Hermissenda crassicornis is a subannual nudibranch species that reproduces
      year-round. 2. There is a significant positive relationship between adult weight,
      diameter of the egg mass, estimated number of eggs per egg mass, and average
      number of eggs per capsule. 3. There is a planktonic veliger stage of 34 days
      minimum at 13 degrees -15 degrees C. 4. Larvae metamorphose on at least three
      species of hydroids. 5. To develop in reasonable numbers to a state competent to
      metamorphose veligers require a diet that includes phytoplankton of larger cell
      size (10-11 microm) than the commonly used Isochrysis and Monochrysis (5 microm).
      6. Although Hermissenda feeds on a wide variety of sessile invertebrate species
      in the ocean, a diet of tunicate alone (Ciona intestinalis) promotes good growth
      and survival in the laboratory. 7. Egg mass deposition is initiated only after
      first copulation, except in the last month of life, and continues from about one
      month post-metamorphosis to death, at about four months post-metamorphosis.
      Generation time (egg-to-egg) may be as short as 2.5 months. 8. A laboratory
      strain of Hermissenda is being established to provide animals of known history
      for research on the neural correlates of behavior. Animals, at least initially,
      are being selected for fast growth rate.

PMID- 20693370
TI  - Additional experiments on the behavior of buds in the ascidian, aplidium
      multiplicatum.
AB  - In a previous paper by the authors, it was suggested that that behavior of
      growing buds, which form a common cloacal system, is affected by a substance
      which is secreted by the mother zooid and diffuses through the tunic. Four sets
      of experiments were made to confirm the existence of the substance, and to get
      more information about the attractant. In the first set, the thorax of a grown
      zooid was removed before budding, and artificial strobilation was induced. In
      this case the buds lacked the mother zooid from the first. In the second, the
      thorax of a grown zooid was removed before budding, together with the tunic
      covering the thorax. In the third, the anterior tip of a mother zooid, thought to
      be a center of secretion, was removed. In the fourth, the experiment was designed
      to show whether a bud is attracted only by its mother and sisters or also by
      other zooids in the same colony. After these operations the behavior of buds was
      followed. The results supported the existence of the attractant. They suggested
      that the time of secretion is not restricted to the period of budding, that the
      site of secretion is not restricted to a special region of the zooid, and that a
      bud is attracted not only by its mother but also by any other zooid in the same
      colony.

PMID- 20693371
TI  - Seasonal burrowing behavior and ecology of aporrhais occidentalis (gastropoda :
      strombacea).
AB  - 1. SCUBA observations and in situ tagging experiments were carried out on a
      population of Aporrhais occidentalis during 1973-1976. Seasonal changes in
      burrowing behavior were quantified by determining the percentage of tagged snails
      found burrowing each month. Gut content analyses were performed at monthly
      intervals to determine if the intensity of feeding activity fluctuates
      seasonally. Empty A. occidentalis shells were collected and examined for evidence
      of predation. 2. Specimens of A. occidentalis alternate between periods of
      epifaunal activity and infaunal quiescence. Tagged snails tended to remain
      burrowed from August through January, but were active on the surface of the
      substrate from February until late summer. Gut content analyses showed that the
      snails fed actively during their epifaunal period, but ceased feeding while
      burrowed. 3. Laboratory attempts to influence burrowing behavior by manipulating
      water temperature were unsuccessful. 4. Published observations on eastern
      Atlantic species of Aporrhais suggest that seasonal burrowing behavior may be
      characteristic of the genus.

PMID- 20693372
TI  - Food-resources and the influence of spatial pattern on feeding in the phoronid
      phoronopsis viridis.
AB  - 1. In the intertidal zone of Bodega Harbor, California, the phoronid, Phoronopsis
      viridis, aggregates in clusters often composed of thousands of tightly aggregated
      individuals (up to 150,000/m(2)). Within a dense cluster, there is a spacing
      problem for expansion of the lophophores. When nearest-neighbor distances are
      small, a stratification of feeding appendages is a workable solution to the
      spacing problem, allowing simultaneous expansion of clustered feeding appendages.
      2. Suspension-feeding specimens of Phoronopsis expand their lophophores and
      collect food items from the turbid near-bottom layers of water. Comparison of
      ingested items with material collected where the phoronids feed indicates a
      preference for small (< 100 microm) organic encrusted mineral grains, floc
      aggregates, and fecal material, all resuspended from the depositional interface.
      Also taken to a lesser extent are plankton bloom species, such as diatoms and
      dinoflagellates. 3. The fact that Phoronopsis forms dense assemblages in the
      intertidal zone has consequences when the community structure of sandflat areas
      is considered. Although it is probable that no single factor can explain
      aggregation in Phoronopsis, two possible factors, constituting strong selection
      pressures for cluster formation, are relative immunity from disturbance by large
      burrowing infauna and protection from predation by crawling predators.

PMID- 20693373
TI  - The life cycle of corymorpha (=euphysora) bigelowi (maas, 1905) and its
      significance in the systematics of corymorphid hydromedusae.
AB  - 1. Five individuals of the corymorphid jellyfish, Euphysora bigelowi Maas, were
      collected in 1973 in Monterey Bay, California, for a range extension of more than
      8,000 km across the northeastern Pacific Ocean. 2. Larvae released by these
      medusae were cultured and the resulting polyps, the first known from this medusa
      genus, are described. 3. The polyps are a Corymorpha, but share some minor
      characteristics with polyps of the corymorphid genus Euphysa. 4. The polyp and
      medusa are assigned the name Corymorpha bigelowi (Maas); the systematic
      implications of this revision are discussed.

PMID- 20693374
TI  - The anatomy of the decapod crustacean auxiliary heart.
AB  - The anatomy of an auxiliary heart found in many decapod crustaceans is described.
      This heart is found at the anterior end of the dorsal median artery before the
      artery divides to supply the cerebral nervous system. The heart is essentially
      two strips of modified somatic muscle located inside a sinus in the dorsal median
      artery. These muscles are innervated by four motoneurons located in the
      supraesophageal ganglion. Sensory innervation and possible neurosecretory
      elements are also described.

PMID- 20693375
TI  - Rectal gland of freshwater stingrays, potamotrygon spp.
      (Chondrichthyes:potamotrygonidae).
AB  - 1. Contrary to some reports, a rectal gland is present in strictly freshwater
      stingrays of South American rivers (Potamotrygon spp.). 2. The gland has the
      location and histological features of the salt-secreting rectal gland of marine
      elasmobranchs, but is much reduced in size and number of tubules. 3. Its residual
      function, if any, is unknown. 4. The rectal gland is associated with prominent
      myeloid lobes, here designated as rectomyeloid bodies. 5. In the absence of
      potamotrygonid fossils, the atrophied rectal gland is strong evidence of marine
      ancestry for the freshwater rays. 6. Both the reduced gland and the loss of urea
      retention in potamotrygonids are indicative of a long history of freshwater
      adaptation.

PMID- 20693376
TI  - Supranormal expiratory airflow after bilateral lung transplantation is associated
      with improved survival.
AB  - RATIONALE: flow volume loops (FVL) in some bilateral lung transplant (BLT) and
      heart-lung transplant (HLT) patients suggest variable extrathoracic obstruction
      in the absence of identifiable causes. These FVLs usually have supranormal
      expiratory and normal inspiratory flow rates (SUPRA pattern). OBJECTIVES:
      characterize the relationship of the SUPRA pattern to predicted donor and
      recipient lung volumes, airway size, and survival. METHODS: we performed a
      retrospective review of adult BLT/HLT patients. We defined the SUPRA FVL pattern
      as: (1) mid-vital capacity expiratory to inspiratory flow ratio (Ve50:Vi50) >
      1.0, (2) absence of identifiable causes of extrathoracic obstruction, and (3)
      Ve50/FVC >= 1.5 s(-1). We calculated predicted total lung capacity (pTLC) ratio
      by dividing the donor pTLC by the recipient pTLC. We measured airway luminal
      areas on thoracic computer tomographic scans. We compared survival in patients
      with and without the SUPRA pattern. MEASUREMENTS AND MAIN RESULTS: the SUPRA FVL
      pattern occurred in 56% of the 89 patients who qualified for the analysis. The
      pTLC ratio of SUPRA and non-SUPRA patients was 1.11 and 0.99, respectively (P =
      0.004). A higher pTLC ratio was correlated with increased probability of the
      SUPRA pattern (P = 0.0072). Airway luminal areas were larger in SUPRA patients (P
      = 0.009). Survival was better in the SUPRA cohort (P = 0.009). CONCLUSIONS: the
      SUPRA FVL pattern was frequent in BLT/HLT patients. High expiratory flows in
      SUPRA patients could result from increased lung elastic recoil or reduced airway
      resistance, both of which could be caused by the pTLC mismatch. Improved survival
      in the SUPRA cohort suggests potential therapeutic approaches to improve outcomes
      in BLT/HLT patients.

PMID- 20693377
TI  - Eight-year trend of acute respiratory distress syndrome: a population-based study
      in Olmsted County, Minnesota.
AB  - RATIONALE: significant progress has been made in understanding the pathogenesis
      of acute respiratory distress syndrome (ARDS). Recent advances in hospital
      practice may have reduced the incidence of this lethal syndrome. OBJECTIVES: to
      observe incidence trends and associated outcomes of ARDS. METHODS: this
      population-based cohort study was conducted in Olmsted County, Minnesota. Using a
      validated screening protocol, investigators identified intensive care patients
      with acute hypoxemia and bilateral pulmonary infiltrates. The presence of ARDS
      was independently confirmed according to American-European Consensus Conference
      criteria. The incidence of ARDS and associated outcomes were compared over the 8
      year study period (2001-2008). MEASUREMENTS AND MAIN RESULTS: over the 8-year
      period, critically ill Olmsted County residents presented with increasing
      severity of acute illness, a greater number of comorbidities, and a higher
      prevalence of major predisposing conditions for ARDS. The ARDS incidence
      decreased significantly from 82.4 to 38.9 per 100,000 person-years during the
      study period (P < 0.001). A decline in hospital-acquired ARDS (P < 0.001) was
      responsible for the fall in the incidence density with no change on admission (P
      = 0.877). Overall, mortality and hospital and intensive care unit lengths of stay
      decreased over time (P < 0.001), whereas the ARDS case-fatality did not change
      significantly. CONCLUSIONS: despite an increase in patients' severity of illness,
      number of comorbidities, and prevalence of major ARDS risk factors, the incidence
      of ARDS in this suburban community decreased by more than half. Correlation of
      the observed findings with changes in health care delivery may have important
      implications for the planning of acute care services in other regions.

PMID- 20693378
TI  - Threshold of biologic responses of the small airway epithelium to low levels of
      tobacco smoke.
AB  - RATIONALE: Epidemiologic data demonstrate that individuals exposed to low levels
      of tobacco smoke have decrements in lung function and higher risk for lung
      disease compared with unexposed individuals. Although this risk is small, low
      level tobacco smoke exposure is so widespread, it is a significant public health
      concern. OBJECTIVES: To identify biologic correlates of this risk we hypothesized
      that, compared with unexposed individuals, individuals exposed to low levels of
      tobacco smoke have biologic changes in the small airway epithelium, the site of
      the first abnormalities associated with smoking. METHODS: Small airway epithelium
      was obtained by bronchoscopy from 121 individuals; microarrays were used to
      assess genome-wide gene expression; urine nicotine and cotinine were used to
      categorize subjects as "nonsmokers," "active smokers," and "low exposure." Gene
      expression data were used to determine the threshold and induction half maximal
      level (ID50) of urine nicotine and cotinine at which the small airway epithelium
      showed abnormal responses. MEASUREMENTS AND MAIN RESULTS: There was no threshold
      of urine nicotine without a small airway epithelial response, and only slightly
      above detectable urine cotinine threshold with a small airway epithelium
      response. The ID50 for nicotine was 25 ng/ml and for cotinine it was 104 ng/ml.
      CONCLUSIONS: The small airway epithelium detects and responds to low levels of
      tobacco smoke with transcriptome modifications. This provides biologic correlates
      of epidemiologic studies linking low-level tobacco smoke exposure to lung health
      risk, identifies the genes most sensitive to tobacco smoke, and defines
      thresholds at which the lung epithelium responds to low levels of tobacco smoke.

PMID- 20693379
TI  - Management of community-acquired pneumonia in adults.
AB  - Despite many advances in medical science, the mortality rate from community
      acquired pneumonia (CAP) has changed little in the past four decades. Death and
      adverse outcomes from CAP result from a complex interplay between the pathogen
      and the host. Newer information about the effect of pneumonia on comorbidity and
      underlying diseases, especially long term, suggests this is an important
      additional axis that differs from the traditional triangular concept of pathogen,
      host defense, and antibiotic treatment. A number of clinical scoring systems have
      been developed to help physicians identify patients with CAP at risk of adverse
      outcomes. None of the criteria have been prospectively demonstrated to avoid late
      intensive care unit transfers or lower mortality, raising interest in the use of
      biomarkers such as procalcitonin. Quantitative bacterial genomic load represents
      a potentially important risk stratification. Optimal antibiotic management
      appears to include use of a macrolide, although the mechanism of benefit remains
      unclear. Attempts to improve CAP outcomes through setting measurable process of
      care standards are to be applauded, but making sure that these standards do not
      become the end in themselves, but rather that the entire process of care is
      improved, remains critical.

PMID- 20693380
TI  - Protective role of peroxisome proliferator-activated receptor-beta/delta in
      septic shock.
AB  - RATIONALE: Peroxisome proliferator-activated receptor (PPAR)-beta/delta is a
      transcription factor that belongs to the PPAR nuclear hormone receptor family,
      but the role of PPAR-beta/delta in sepsis is unknown. OBJECTIVES: We investigated
      the role of PPAR-beta/delta in murine models of LPS-induced organ injury and
      dysfunction and cecal ligation and puncture (CLP)-induced polymicrobial sepsis.
      METHODS: Wild-type (WT) and PPAR-beta/delta knockout (KO) mice and C57BL/6 mice
      were subjected to LPS for 16 hours. C57BL/6 mice received the PPAR-beta/delta
      agonist GW0742 (0.03 mg/kg intravenously, 1 h after LPS) or GW0742 plus the PPAR
      beta/delta antagonist GSK0660 (0.1 mg/kg intravenously, 30 min before LPS). CD-1
      mice subjected to CLP received GW0742 or GW0742 plus GSK0660. MEASUREMENTS AND
      MAIN RESULTS: In PPAR-beta/delta KO mice, endotoxemia exacerbated organ injury
      and dysfunction (cardiac, renal, and hepatic) and inflammation (lung) compared
      with WT mice. In C57BL/6 mice subjected to endotoxemia, GW0742 significantly (1)
      attenuated organ (cardiac and renal) dysfunction and inflammation (lung); (2)
      increased the phosphorylation of Akt and glycogen synthase kinase (GSK)-3beta;
      (3) attenuated the increase in extracellular signal-regulated kinase (ERK)1/2 and
      signal transducer and activator of transcription (STAT)-3 phosphorylation; and
      (4) attenuated the activation of nuclear factor (NF)-kappaB and the expression of
      inducible nitric oxide synthase (iNOS). In CD-1 mice subjected to CLP, GW0742
      improved 10-day survival. All the observed beneficial effects of GW0742 were
      attenuated by the PPAR-beta/delta antagonist GSK0660. CONCLUSIONS: PPAR
      beta/delta protects against multiple organ injury and dysfunction, and
      inflammation caused by endotoxic shock and improves survival in polymicrobial
      sepsis by a mechanism that may involve activation of Akt and inhibition of GSK
      3beta and NF-kappaB.

PMID- 20693381
TI  - Nosocomial pneumonia in the intensive care unit acquired by mechanically
      ventilated versus nonventilated patients.
AB  - RATIONALE: Most current information on hospital-acquired pneumonia (HAP) is
      extrapolated from patients with ventilator-associated pneumonia (VAP). No studies
      have evaluated HAP in the intensive care unit (ICU) in nonventilated patients.
      OBJECTIVES: To compare pneumonia acquired in the ICU by mechanically ventilated
      versus nonventilated patients. METHODS: We prospectively collected 315 episodes
      of ICU-acquired pneumonia. We compared clinical and microbiologic characteristics
      of patients with VAP (n = 164; 52%) and nonventilator ICU-acquired pneumonia (NV
      ICUAP; n = 151; 48%). Among NV-ICUAP patients, 79 (52%) needed subsequent
      intubation. MEASUREMENTS AND MAIN RESULTS: Compared with NV-ICUAP, patients with
      VAP were more severe (APACHE-II 17 +/- 6 vs. 15 +/- 5; P < 0.001) and pneumonia
      occurred later in the ICU (8 +/- 8 vs. 5 +/- 6 d; P < 0.001). Etiologic diagnosis
      (117, 71% vs. 64, 42%; P < 0.001), nonfermenting (28% vs. 15%; P = 0.009) and
      enteric gram-negative bacilli (26% vs. 13%; P = 0.006), and methicillin-sensitive
      Staphylococcus aureus (14% vs. 6%; P = 0.031) were more frequent in VAP, likely
      caused by more patients with lower respiratory tract samples cultured (100% vs.
      84%; P < 0.001). However, in patients with defined etiology only, the proportion
      of pathogens was similar between groups, except for a higher proportion of
      Streptococcus pneumoniae in NV-ICUAP (P = 0.045). The hospital mortality also was
      similar. CONCLUSIONS: Despite a lower proportion of pathogens in NV-ICUAP
      compared with VAP, the type of isolates and outcomes are similar regardless of
      whether pneumonia is acquired or not during ventilation, indicating they may
      depend on patients' underlying severity rather than previous intubation. With the
      diagnostic techniques currently recommended by guidelines, both types of patients
      might receive similar empiric antibiotic treatment.

PMID- 20693383
TI  - "Why am I out of the loop?" attributions influence responses to information
      exclusion.
AB  - Studies show the importance of information sharing in decision making. However,
      information sharing also affects intrapersonal perceptions and group dynamics.
      Three experiments demonstrated that out-of-the-loop individuals experienced
      thwarted needs (e.g., belonging) and decreased trust and liking of group members.
      Experiment 1 showed these deleterious effects only occurred when information
      exclusion appeared intentional. Experiment 2 established that constructive
      motives could mitigate negative effects of intentional information exclusion.
      Experiment 3 showed that unintentional information exclusion deflated
      participants only when perceived as preventable. These experiments also provided
      evidence for a mediating process. Information exclusion, particularly when ill
      intentioned or preventable, signals poor group standing, leading to deleterious
      psychological effects.

PMID- 20693382
TI  - Targeted delivery of amikacin into granuloma.
AB  - RATIONALE: Nontuberculous mycobacterial (NTM) infection is a growing problem in
      the United States and remains underrecognized in the developing world. The
      management of NTM infections is further complicated by several factors, including
      the need to use high systemic doses of toxic agents, the length of therapy, and
      the development of drug resistance. OBJECTIVES: We have evaluated the use of
      monocyte-derived dendritic cells (DCs) as a delivery vehicle for a luminescent
      derivative of amikacin prepared by conjugation to fluorescein isothiocyanate
      (FITC) (amikacin-FITC) into granulomas formed in the tissues of mice infected
      with Mycobacterium avium. METHODS: Amikacin-FITC was prepared and quantitative
      fluorescence was used to track the intracellular uptake of this modified
      antibiotic. The antibiotic activity of amikacin-FITC was also determined to be
      comparable to unmodified amikacin against M. avium. Amikacin-FITC-loaded DCs were
      first primed with M. avium, and then the cells were injected into the tail vein
      of infected mice. After 24 hours, the mice were sacrificed and the tissues were
      analyzed under fluorescence microscope. MEASUREMENTS AND MAIN RESULTS: We found
      that we were able to deliver amikacin into granulomas in a mouse model of
      disseminated mycobacterial infection. No increase in levels of monocyte
      chemoattractant protein-1 and its CCR2 as markers of inflammation were found when
      DCs were treated with amikacin-FITC. CONCLUSIONS: DC-based drug delivery may be
      an adjunct and useful method of delivering high local concentrations of
      antibiotics into mycobacterial granulomas.

PMID- 20693384
TI  - Being "in" with the in-crowd: the effects of social exclusion and inclusion are
      enhanced by the perceived essentialism of ingroups and outgroups.
AB  - Social belonging is an essential human need. Belonging to social groups serves an
      important role in shaping our social identities. Nonetheless, research indicates
      that exclusion by ingroup and outgroup members seems equally aversive. The
      current studies test the hypothesis that unlike more trivial groups (e.g.,
      smoking or computer preferences), highly essentialized groups may lead to
      differential effects of ingroup versus outgroup rejection. Consistent with this,
      exclusion and inclusion by racial ingroup members (relative to racial outgroup
      members) exacerbated the sting of rejection and the glow of inclusion (Study 1).
      In a second study, direct manipulations of essentialist beliefs about ingroups
      and outgroups (i.e., political affiliations) led to the same results. These
      results offer a novel demonstration that essentialized ingroup-outgroup
      distinctions enhance the sting of social exclusion and the positivity of social
      inclusion.

PMID- 20693385
TI  - Having the power to forgive: when the experience of power increases interpersonal
      forgiveness.
AB  - The present research examined the association between power, defined in terms of
      experienced control over outcomes and resources in a relationship, and
      interpersonal forgiveness. Based on recent findings in the literature suggesting
      that power is associated with goal directedness, it was hypothesized that high
      levels of experienced power should facilitate forgiveness, in particular in
      relationships of strong commitment. The results of three studies, using both
      correlational and experimental designs, supported this prediction: Power was
      positively associated with forgiveness, but this effect was stronger in
      relationships of strong (rather than weak) commitment. This pattern of results
      was observed for both the inclination to forgive hypothetical offenses and actual
      forgiveness regarding a past offense. Study 3 provided some preliminary evidence
      for the role of rumination in the link between power and forgiveness.
      Implications of these findings for the literature on forgiveness and the
      literature on social power are discussed.

PMID- 20693386
TI  - Person categorization and automatic racial stereotyping effects on weapon
      identification.
AB  - Prior stereotyping research provides conflicting evidence regarding the
      importance of person categorization along a particular dimension for the
      automatic activation of a stereotype corresponding to that dimension. Experiment
      1 replicated a racial stereotyping effect on object identification and examined
      whether it could be attenuated by encouraging categorization by age. Experiment 2
      employed socially complex person stimuli and manipulated whether participants
      categorized spontaneously or by race. In Experiment 3, the distinctiveness of the
      racial dimension was manipulated by having Black females appear in the context of
      either Black males or White females. The results indicated that conditions
      fostering categorization by race consistently produced automatic racial
      stereotyping and that conditions fostering nonracial categorization can eliminate
      automatic racial stereotyping. Implications for the relation between automatic
      stereotype activation and dimension of categorization are discussed.

PMID- 20693387
TI  - The cost of self-protection: threat response and performance as a function of
      autonomous and controlled motivations.
AB  - Seventy-seven undergraduates, primed for autonomous or controlled motivation,
      were videotaped and physiologically monitored during a stressful interview and
      subsequent speech. Interview videotapes were coded for behavioral measures of
      threat response; speech videotapes were coded for performance. It was
      hypothesized that relative to controlled motivation, autonomous motivation would
      decrease interview threat response and enhance speech performance, and that
      threat response would mediate the effect of motivation on performance. Results
      support the prediction across measures of verbal, paralinguistic, smiling, vocal
      fundamental frequency, and cardiovascular response. Autonomously primed
      participants continued to show less cardiovascular threat throughout the later
      speech and gave better speeches. Finally, speech performance was mediated by
      interview threat response. Results demonstrate that relative to controlled
      motivation, autonomous motivation lowers threat response, which enhances
      performance.

PMID- 20693388
TI  - Ingroup glorification, moral disengagement, and justice in the context of
      collective violence.
AB  - What aspects of ingroup identification can lead people to resist justice for the
      victims of their ingroup's mistreatment? In three studies carried out in the
      United States and United Kingdom, in which participants read reports of
      mistreatment of prisoners and civilians by coalition troops in the Iraq war,
      ingroup glorification, but not ingroup attachment or other individual-difference
      variables, was a key predictor of lesser demands for justice, but only when the
      perpetrators belonged to the ingroup. This effect of glorification was mediated
      by two moral disengagement mechanisms focusing on the outgroup: minimization of
      the emotional suffering of the victims' families and explicit dehumanization of
      the victim group. These findings further reinforce the difference between
      glorification and other forms of ingroup identification, demonstrating that
      glorification is problematic in maintaining and fostering intergroup relations
      because of its connection to moral disengagement.

PMID- 20693389
TI  - Influence of contingency awareness on neural, electrodermal and evaluative
      responses during fear conditioning.
AB  - In an fMRI study, effects of contingency awareness on conditioned responses were
      assessed in three groups comprising 118 subjects. A differential fear
      conditioning paradigm with visual conditioned stimuli, an electrical
      unconditioned stimulus and two distractors was applied. The instructed aware
      group was informed about the contingencies, whereas the distractors prevented
      contingency detection in the unaware group. The third group (learned aware) was
      not informed about the contingencies, but learned them despite the distractors.
      Main effects of contingency awareness on conditioned responses emerged in several
      brain structures. Post hoc tests revealed differential dorsal anterior cingulate,
      insula and ventral striatum responses in aware conditioning only, whereas the
      amygdala was activated independent of contingency awareness. Differential
      responses of the hippocampus were specifically observed in learned aware
      subjects, indicating a role in the development of contingency awareness. The
      orbitofrontal cortex showed varying response patterns: lateral structures showed
      higher responses in instructed aware than unaware subjects, the opposite was true
      for medial parts. Conditioned subjective and electrodermal responses emerged only
      in the two aware groups. These results confirm the independence of conditioned
      amygdala responses from contingency awareness and indicate specific neural
      circuits for different aspects of fear acquisition in unaware, learned aware and
      instructed aware subjects.

PMID- 20693390
TI  - Forming a negative impression of another person correlates with activation in
      medial prefrontal cortex and amygdala.
AB  - Neural correlates involved in the formation of negative impression from face were
      investigated using event-related functional magnetic resonance imaging and a
      partial conditioning paradigm. Eighteen normal volunteers underwent imaging while
      they viewed the faces of two unfamiliar individuals: one individual's face was
      partially accompanied by negative emotion but the other's was not. After the
      volunteers learned the relationship between the faces and the emotion, they
      formed a more negative impression of the person's face when the emotion was
      presented. Subtraction analysis of the individuals' neutral faces revealed
      activation in the dorsal anterior cingulate cortex and superior temporal sulcus,
      but this activity did not correlate with the change of impression from face. On
      the other hand, the response in the left amygdala negatively correlated with the
      change of impression from face in the first run. Time modulation analysis
      revealed that activity in the dorsomedial prefrontal cortex associated with
      negative emotion was the largest in the initial part of the acquisition. These
      results suggest that a negative impression from face may be formed by
      orchestrated activity in the dorsomedial prefrontal cortex, dorsal anterior
      cingulate cortex and amygdala, and that the activity has a prominent role in the
      initial acquisition of negative emotion.

PMID- 20693391
TI  - Chronic treatment with vitamin D lowers arterial blood pressure and reduces
      endothelium-dependent contractions in the aorta of the spontaneously hypertensive
      rat.
AB  - Vitamin D has cardiovascular protective effects besides regulating calcium
      homeostasis. To examine the chronic in vivo effect of a physiological dose of
      1,25-dihydroxyvitamin D(3) on the occurrence of endothelium-dependent
      contractions, spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY)
      were treated with the vitamin D derivative for 6 wk. The serum 1,25
      dihydroxyvitamin D(3) level of both treated WKY and SHR was significantly higher
      than in untreated rats while the mean arterial blood pressure of the treated SHR
      was significantly lower than that of control SHR. Aortic rings with or without
      endothelium were studied in conventional organ chambers for isometric force
      measurement. Confocal microscopy was used to measure the cytosolic free calcium
      concentration (with the fluorescent dye fluo 4) and reactive oxygen species (ROS;
      with dichlorodihydrofluorescein diacetate). Reverse transcription PCR and Western
      blotting were used to determine the mRNA and protein expression level of
      cyclooxygenase-1 (COX-1), prostacyclin synthase, and thromboxane synthase. The
      endothelium-dependent concentration-contraction curves to both acetylcholine- and
      A-23187-induced contractions were shifted to the right in aortas from treated SHR
      but not from treated WKY. The chronic treatment normalized the relaxations of
      contracted preparations to acetylcholine. There were no significant differences
      in the increases in cytosolic free calcium concentration evoked by acetylcholine
      and A-23187 between control and treated groups. The endothelial ROS level was
      higher in SHR than WKY aortas and reduced by the chronic treatment. The gene and
      protein expression studies indicated that the overexpression of COX-1 observed in
      SHR aorta was reduced by the chronic treatment. These results demonstrate that
      chronic treatment with 1,25-dihydroxyvitamin D(3) modulates vascular tone and
      this modulation is accompanied by a lowered blood pressure, reduced expression of
      COX-1 mRNA and protein, and reduced ROS level in SHR. The reduction in
      endothelium-dependent contractions does not involve the surge in endothelial
      cytosolic calcium concentration that initiates the contractions.

PMID- 20693393
TI  - Isolation of interstitial fluid in skin during volume expansion: evaluation of a
      method in pigs.
AB  - The ability to isolate interstitial fluid (IF) from skin would make it possible
      to study the microcirculation and proteins in this environment both during normal
      and pathophysiological conditions. Traditional IF sampling using implanted wicks
      suffer from low volumes with risk of contamination by local inflammatory,
      intracellular, and vascular proteins. To sample larger volumes of true IF, a
      recently described tissue centrifugation method was compared with dry and wet
      wicks from porcine skin under normal conditions and following volume expansion.
      With all three methods, volume expansion caused a significant lowering of
      interstitial colloid osmotic pressure as expected, and the fluid was similar to
      plasma when compared using size-exclusion HPLC. The centrifugation method was
      superior with respect to isolating larger amounts of true IF for further studies.
      Mass spectrometry of IF sampled with centrifugation showed that most of the
      proteins reflected the major plasma proteins with some tissue-specific proteins
      like decorin, gelsolin, and orosomucoid-1. Lumican, pigment epithelium-derived
      factor, and fatty acid-binding protein 4 were only identified in IF after volume
      expansion, possibly reflecting a local response to increased fluid filtration.
      Tissue centrifugation to collect IF from skin should be applicable to both
      clinical and experimental studies on IF balance during different
      pathophysiological conditions and interventions.

PMID- 20693392
TI  - Interleukin-18 induces EMMPRIN expression in primary cardiomyocytes via JNK/Sp1
      signaling and MMP-9 in part via EMMPRIN and through AP-1 and NF-kappaB
      activation.
AB  - IL-18 and the extracellular matrix metalloproteinase (MMP) inducer (EMMPRIN)
      stimulate the expression of proinflammatory cytokines and MMPs and are elevated
      in myocardial hypertrophy, remodeling, and failure. Here, we report several novel
      findings in primary cardiomyocytes treated with IL-18. First, IL-18 activated
      multiple transcription factors, including NF-kappaB (p50 and p65), activator
      protein (AP)-1 (cFos, cJun, and JunD), GATA, CCAAT/enhancer-binding protein,
      myocyte-specific enhancer-binding factor, interferon regulatory factor-1, p53,
      and specific protein (Sp)-1. Second, IL-18 induced EMMPRIN expression via myeloid
      differentiation primary response gene 88/IL-1 receptor-associated kinase/TNF
      receptor-associated factor-6/JNK-dependent Sp1 activation. Third, IL-18 induced a
      number of MMP genes, particularly MMP-9, at a rapid rate as well as tissue
      inhibitor of metalloproteinase (TIMP)-1 and TIMP-3 at a slower rate. Finally, the
      IL-18 induction of MMP-9 was mediated in part via EMMPRIN and through JNK- and
      ERK-dependent AP-1 activation and p38 MAPK-dependent NF-kappaB activation. These
      results suggest that the elevated expression of IL-18 during myocardial injury
      and inflammation may favor EMMPRIN and MMP induction and extracellular matrix
      degradation. Therefore, targeting IL-18 or its signaling pathways may be of
      potential therapeutic benefit in adverse remodeling.

PMID- 20693394
TI  - Insufficient cutaneous vasoconstriction leading up to and during syncopal
      symptoms in the heat stressed human.
AB  - As much as 50% of cardiac output can be distributed to the skin in the
      hyperthermic human, and therefore the control of cutaneous vascular conductance
      (CVC) becomes critical for the maintenance of blood pressure. Little is known
      regarding the magnitude of cutaneous vasoconstriction in profoundly hypotensive
      individuals while heat stressed. This project investigated the hypothesis that
      leading up to and during syncopal symptoms associated with combined heat and
      orthostatic stress, reductions in CVC are inadequate to prevent syncope. Using a
      retrospective study design, we evaluated data from subjects who experienced
      syncopal symptoms during lower body negative pressure (N = 41) and head-up tilt
      (N = 5). Subjects were instrumented for measures of internal temperature, forearm
      skin blood flow, arterial pressure, and heart rate. CVC was calculated as skin
      blood flow/mean arterial pressure * 100. Data were obtained while subjects were
      normothermic, immediately before an orthostatic challenge while heat stressed,
      and at 5-s averages for the 2 min preceding the cessation of the orthostatic
      challenge due to syncopal symptoms. Whole body heat stress increased internal
      temperature (1.25 +/- 0.3 degrees C; P < 0.001) and CVC (29 +/- 20 to 160 +/- 58
      CVC units; P < 0.001) without altering mean arterial pressure (83 +/- 7 to 82 +/-
      6 mmHg). Mean arterial pressure was reduced to 57 +/- 9 mmHg (P < 0.001)
      immediately before the termination of the orthostatic challenge. At test
      termination, CVC decreased to 138 +/- 61 CVC units (P < 0.001) relative to before
      the orthostatic challenge but remained approximately fourfold greater than when
      subjects were normothermic. This negligible reduction in CVC during pronounced
      hypotension likely contributes to reduced orthostatic tolerance in heat-stressed
      humans. Given that lower body negative pressure and head-up tilt are models of
      acute hemorrhage, these findings have important implications with respect to
      mechanisms of compromised blood pressure control in the hemorrhagic individual
      who is also hyperthermic (e.g., military personnel, firefighters, etc.).

PMID- 20693395
TI  - Tongxinluo reduces myocardial no-reflow and ischemia-reperfusion injury by
      stimulating the phosphorylation of eNOS via the PKA pathway.
AB  - The objective of the present study was to investigate whether pretreatment with
      single low loading dose of tongxinluo (TXL), a traditional Chinese medicine, 1 h
      before myocardial ischemia could attenuate no-reflow and ischemia-reperfusion
      injury by regulating endothelial nitric oxide synthase (eNOS) via the PKA
      pathway. In a 90-min ischemia and 3-h reperfusion model, minipigs were randomly
      assigned to the following groups: sham, control, TXL (0.05 g/kg, gavaged 1 h
      before ischemia), TXL + H-89 (a PKA inhibitor, intravenously infused at a dose of
      1.0 MUg.kg(-1).min(-1) 30 min before ischemia), and TXL + N(omega)-nitro-L
      arginine (L-NNA; an eNOS inhibitor, intravenously administered at a dose of 10
      mg/kg 30 min before ischemia). TXL decreased creatine kinase (CK) activity (P <
      0.05) and reduced the no-reflow area from 48.6% to 9.5% and infarct size from
      78.5% to 59.2% (P < 0.05), whereas these effects of TXL were partially abolished
      by H-89 and completely reversed by L-NNA. TXL elevated PKA activity and the
      expression of PKA, Thr(198) phosphorylated PKA, Ser(1179) phosphorylated eNOS,
      and Ser(635) phosphorylated eNOS in the ischemic myocardium. H-89 repressed the
      TXL-induced enhancement of PKA activity and phosphorylation of eNOS at Ser(635),
      and L-NNA counteracted the phosphorylation of eNOS at Ser(1179) and Ser(635)
      without an apparent influence on PKA activity. In conclusion, pretreatment with a
      single low loading dose of TXL 1 h before ischemia reduces myocardial no-reflow
      and ischemia-reperfusion injury by upregulating the phosphorylation of eNOS at
      Ser(1179) and Ser(635), and this effect is partially mediated by the PKA pathway.

PMID- 20693396
TI  - Sildenafil added to sitaxsentan in overcirculation-induced pulmonary arterial
      hypertension.
AB  - Experimental left-to-right shunt-induced pulmonary arterial hypertension (PAH)
      can be partially prevented by the endothelin-A receptor blocker sitaxsentan or by
      the phosphodiesterase-5 inhibitor sildenafil. We hypothesized that the combined
      administration of these drugs would completely prevent shunt-induced PAH, arguing
      in favor of a major role of endothelial dysfunction in the initiation of the
      disease. Twenty-four 3-wk-old piglets were randomized to a sham operation or to
      placebo, sitaxsentan therapy, or sitaxsentan combined with sildenafil after the
      anastomosis of the left subclavian artery to the pulmonary arterial trunk. Three
      months later, the animals underwent a hemodynamic evaluation, followed by
      pulmonary tissue sampling for morphometry and quantitative real-time PCR for
      endothelin-1, angiopoietin-1, and bone morphogenetic protein receptor (BMPR)
      signaling molecules. Three months of left-to-right shunting induced an increase
      in pulmonary vascular resistance (PVR) and medial thickness, an overexpression of
      endothelin-1, and angiopoietin-1 and decreased expressions of BMPR-2 and BMPR-1A.
      Sitaxsentan partially prevented a shunt-induced increase in PVR, medial
      thickness, and associated biological disturbances. Sildenafil combined with
      sitaxsentan normalized PVR, medial thickness, and the expression of endothelin-1.
      However, the expression of angiopoietin-1 remained increased, and the expressions
      of BMPR-1A and BMPR-2 were incompletely returned to normal. The coupling of right
      ventricular end-systolic to arterial elastances was maintained in all
      circumstances. Sitaxsentan combined with sildenafil prevents shunt-induced PAH
      more effectively than sitaxsentan alone, suggesting a major role for the targeted
      signaling pathways in the initiation of the disease. Sitaxsentan alone or
      combined with sildenafil did not affect right ventricular function.

PMID- 20693397
TI  - Cardiac function is not significantly diminished in hearts isolated from young
      caveolin-1 knockout mice.
AB  - Matrix metalloproteinases (MMPs) are known to degrade components of the
      extracellular matrix. More recently, in myocardial oxidative stress injury
      including ischemia-reperfusion, MMP-2 is activated and degrades troponin I and
      alpha-actinin. MMP activity is regulated at several levels. We recently showed
      that MMP-2 is localized in the caveolae of cardiomyocytes and is negatively
      regulated by caveolin-1 (Cav-1). The caveolin scaffolding domain of Cav-1
      inhibits MMP-2 proteolytic activity in vitro, and Cav-1(-/-) mouse hearts have
      increased MMP-2 activity compared with controls. Whether this increase in MMP-2
      activity translates to impaired cardiac function is unknown. Hearts isolated from
      Cav-1(-/-) mice and their wild-type controls were perfused as isolated working
      hearts and physiologically challenged with increasing increments of left atrial
      preload (7-22.5 mmHg). The hearts were then pharmacologically challenged with
      increasing concentrations of isoproterenol (0.1-100 nM). Functionally, the Cav-1(
      /-) hearts were similar to the controls in heart rate, peak systolic pressure,
      developed pressure, and rate pressure product. At higher preload pressures, the
      Cav-1(-/-) hearts outperformed the control hearts. Coronary flow was
      significantly higher in Cav-1(-/-) hearts under all conditions. The highest
      concentration of isoproternol increased the heart rate of Cav-1(-/-) hearts more
      than in controls. Western blot analysis revealed no significant changes in
      troponin I or alpha-actinin between Cav-1(-/-) hearts and their controls. There
      was a significant loss of MMP-2 from both knockout and control hearts during the
      perfusion. In summary, despite the loss of Cav-1, Cav-1(-/-) hearts show similar
      or better cardiac function compared with wild-type hearts following physiological
      challenge or beta-adrenergic stimulation in vitro, and this appears unrelated to
      changes in MMP-2.

PMID- 20693398
TI  - Protein complex formation with heat shock protein 90 in chronic hypoxia-induced
      pulmonary hypertension in newborn piglets.
AB  - Aberrant interactions between heat shock protein (Hsp)90 and its client proteins
      could contribute to pulmonary hypertension. We tested the hypotheses that 1) the
      interaction between Hsp90 and its known client protein, endothelial nitric oxide
      synthase (eNOS), is impaired in pulmonary resistance arteries (PRAs) from piglets
      with pulmonary hypertension caused by exposure to 3 or 10 days of hypoxia and 2)
      Hsp90 interacts with the prostanoid pathway proteins prostacyclin synthase (PGIS)
      and/or thromboxane synthase (TXAS). We also determined whether Hsp90 antagonism
      with geldanamycin alters the agonist-induced synthesis of prostacyclin and
      thromboxane or alters PRA responses to these prostaglandin metabolites. Compared
      with normoxic piglets, less eNOS coimmunoprecipitated with Hsp90 in PRAs from
      hypoxic piglets. Despite reduced Hsp90-eNOS interactions, dilation to ACh was
      enhanced in geldanamycin-treated PRAs from hypoxic, but not normoxic, piglets. In
      PRAs from all groups of piglets, PGIS and TXAS coimmunoprecipitated with Hsp90.
      Geldanamycin reduced the ACh-induced synthesis of prostacyclin and thromboxane
      and altered responses to the thromboxane mimetic U-46619 in PRAs from all groups.
      Although geldanamycin enhanced responses to prostacyclin in PRAs from both groups
      of hypoxic piglets, geldanamycin had no effect on prostacyclin responses in PRAs
      from either group of normoxic piglets. Our findings indicate that Hsp90
      influences both prostanoid and eNOS signaling in the pulmonary circulation of
      newborn piglets and that the impact of pharmacological inhibition of Hsp90 on
      these signaling pathways is altered during exposure to chronic hypoxia.

PMID- 20693399
TI  - Postconditioning effect of granulocyte colony-stimulating factor is mediated
      through activation of risk pathway and opening of the mitochondrial KATP
      channels.
AB  - Granulocyte colony-stimulating factor (G-CSF) has been reported to improve
      cardiac function after myocardial infarction. However, whether postinfarct acute
      effect of G-CSF is mediated through the same signaling pathways as those of
      ischemic postconditioning is still unclear. We examined the postinfarct acute
      effect of G-CSF on myocardial infarct size and its precise molecular mechanism.
      Japanese white rabbits underwent 30 min of ischemia and 48 h of reperfusion.
      Rabbits were intravenously injected 10 MUg/kg of G-CSF (G-CSF group) or saline
      (control group) immediately after reperfusion. The wortmannin + G-CSF, PD-98059 +
      G-CSF, N(omega)-nitro-L-arginine methyl ester (l-NAME) + G-CSF, and 5
      hydroxydecanoic acid sodium salt (5-HD) + G-CSF groups were respectively injected
      with wortmannin (0.6 mg/kg), PD-98059 (0.3 mg/kg), L-NAME (10 mg/kg), and 5-HD (5
      mg/kg) 5 min before G-CSF administration. Myocardial infarct size was calculated
      as a percentage of the risk area of the left ventricle. Western blot analysis was
      performed to examine the signals such as protein kinase B (Akt), extracellular
      signal-regulated protein kinase (ERK), eNOS, p70S6 kinase (p70S6K), and glycogen
      synthase kinase-3beta (GSK3beta) in the ischemic myocardium after 48 h of
      reperfusion. The infarct size was significantly smaller in the G-CSF group (26.7
      +/- 2.7%) than in the control group (42.3 +/- 4.6%). The infarct size-reducing
      effect of G-CSF was completely blocked by wortmannin (44.7 +/- 4.8%), PD-98059
      (38.3 +/- 3.9%), L-NAME (42.1 +/- 4.2%), and 5-HD (42.5 +/- 1.7%). Wortmannin, PD
      98059, L-NAME, or 5-HD alone did not affect the infarct size. Western blotting
      showed higher myocardial expression of phospho-Akt, phospho-ERK, phosho-eNOS,
      phosho-p70S6K, and phosho-GSK3beta at 10 min and 48 h after reperfusion in the G
      CSF group than in the control group. In conclusion, postreperfusion G-CSF
      administration reduces myocardial infarct size via activation of
      phosphatidylinositol 3-kinase-Akt and ERK prosurvival signaling pathways and
      their downstream targets eNOS, p70S6 kinase, GSK3beta, and mitochondrial ATP
      dependent K(+) channel.

PMID- 20693400
TI  - SEWAL: an open-source platform for next-generation sequence analysis and
      visualization.
AB  - Next-generation DNA sequencing platforms provide exciting new possibilities for
      in vitro genetic analysis of functional nucleic acids. However, the size of the
      resulting data sets presents computational and analytical challenges. We present
      an open-source software package that employs a locality-sensitive hashing
      algorithm to enumerate all unique sequences in an entire Illumina sequencing run
      (~ 10(8) sequences). The algorithm results in quasilinear time processing of
      entire Illumina lanes (~ 10(7) sequences) on a desktop computer in minutes. To
      facilitate visual analysis of sequencing data, the software produces three
      dimensional scatter plots similar in concept to Sewall Wright and John Maynard
      Smith's adaptive or fitness landscape. The software also contains functions that
      are particularly useful for doped selections such as mutation frequency analysis,
      information content calculation, multivariate statistical functions (including
      principal component analysis), sequence distance metrics, sequence searches and
      sequence comparisons across multiple Illumina data sets. Source code, executable
      files and links to sample data sets are available at
      http://www.sourceforge.net/projects/sewal.

PMID- 20693401
TI  - Modulation of NF-kappaB and hypoxia-inducible factor--1 by S-nitrosoglutathione
      does not alter allergic airway inflammation in mice.
AB  - Induction of nitric oxide synthase (NOS)-2 and production of nitric oxide (NO)
      are common features of allergic airway disease. Conditions of severe asthma are
      associated with deficiency of airway S-nitrosothiols, a biological product of NO
      that can suppress inflammation by S-nitrosylation of the proinflammatory
      transcription factor, NF-kappaB. Therefore, restoration of airway S-nitrosothiols
      might have therapeutic benefit, and this was tested in a mouse model of ovalbumin
      (OVA)-induced allergic inflammation. Naive or OVA-sensitized animals were
      administered S-nitrosoglutathione (GSNO; 50 MUl, 10 mM) intratracheally before
      OVA challenge and analyzed 48 hours later. GSNO administration enhanced lung
      tissue S-nitrosothiol levels and reduced NF-kappaB activity in OVA-challenged
      animals compared with control animals, but did not lead to significant changes in
      total bronchoalveolar lavage cell counts, differentials, or mucus metaplasia
      markers. Administration of GSNO also altered the activation of hypoxia-inducible
      factor (HIF)-1, leading to HIF-1 activation in naive mice, but suppressed HIF-1
      activation in OVA-challenged mice. We assessed the contribution of endogenous
      NOS2 in regulating NF-kappaB and/or HIF-1 activation and allergic airway
      inflammation using NOS2(-/-) mice. Although OVA-induced NF-kappaB activation was
      slightly increased in NOS2(-/-) mice, associated with small increases in
      bronchoalveolar lavage neutrophils, other markers of allergic inflammation and
      HIF-1 activation were similar in NOS2(-/-) and wild-type mice. Collectively, our
      studies indicate that instillation of GSNO can suppress NF-kappaB activation
      during allergic airway inflammation, but does not significantly affect overall
      markers of inflammation or mucus metaplasia, thus potentially limiting its
      therapeutic potential due to effects on additional signaling pathways, such as
      HIF-1.

PMID- 20693402
TI  - Diesel exhaust particulate--exposed macrophages cause marked endothelial cell
      activation.
AB  - Exposure to air pollution containing diesel exhaust particulate (DEP) is linked
      to adverse cardiovascular events. This study tested the hypothesis that DEP not
      only causes direct endothelial cell injury, but also induces indirect endothelial
      cell activation via the release of soluble proinflammatory cytokines from
      macrophages. Human umbilical vein endothelial cells (HUVECs) and monocyte-derived
      macrophages (MDMs) were incubated with DEP (1-100 MUg/ml; 24 h). Supernatants
      were analyzed for monocyte chemotactic protein (MCP)-1, IL6, IL8, and TNF-alpha.
      Indirect actions of DEP were investigated by incubating HUVECs with conditioned
      media from DEP-exposed MDMs in the presence and absence of the TNF-alpha
      inhibitor, etanercept. A modified Boyden chamber assay was used to determine
      whether HUVECs treated in this manner induced monocyte chemotaxis. Direct
      incubation with DEP induced a modest increase in MCP-1 concentration, but had no
      effect on IL-6 or IL-8 release from HUVECs. In contrast, direct treatment of MDMs
      with DEP had no effect on MCP-1, but elevated IL-8 and TNF-alpha concentrations.
      Incubation with conditioned media from DEP-exposed MDMs caused a dramatic
      amplification in MCP-1 and IL-6, but not IL-8, release from HUVECs. The
      potentiation of HUVEC activation was suppressed by TNF-alpha inhibition. MCP-1-
      and IL-6-containing HUVEC supernatants caused increased monocyte chemotaxis that
      was not inhibited by anti-MCP-1 antibodies. We conclude that DEP has only modest
      direct endothelial effects. In contrast, proinflammatory cytokines released from
      particle-laden MDMs appear to exacerbate endothelial activation after DEP
      exposure.

PMID- 20693403
TI  - Plasminogen activation by airway smooth muscle is regulated by type I collagen.
AB  - Plasmin, the activated protease product of plasminogen, is involved in collagen
      remodeling, and is strongly implicated in asthma pathophysiology by recent genome
      wide association studies. This study examines plasminogen "activation" by airway
      smooth muscle cells, and its regulation in a fibrotic environment created by
      culture on type I collagen and incubation with transforming growth factor (TGF)
      beta. Urokinase plasminogen activator (uPA) activity was detected in the
      supernatants of human airway smooth muscle cell cultures maintained in serum-free
      conditions. Incubation with plasminogen (1.5-50.0 MUg/ml, 24 h) increased plasmin
      activity in a concentration-dependent manner (P < 0.001). uPA activity was higher
      in cultures maintained on fibrillar type I collagen substrata than in those on
      plastic, as was plasmin activity after incubation with plasminogen (20 MUg/ml).
      Pretreatment with TGF-beta (100 pM) for 18 hours inhibited plasminogen activation
      by airway smooth muscle cells maintained on plastic, but not on collagen. TGF
      beta stimulated an increase in the level of uPA mRNA in airway smooth muscle
      cells grown on collagen, but not on plastic. Reducing the levels of beta1
      integrin collagen receptor, using interference RNA, attenuated plasmin formation
      by airway smooth muscle cells grown on collagen, and restored the inhibitory
      effect of TGF-beta. This study shows that airway smooth muscle activation of
      plasminogen by uPA is accelerated in a collagen-rich environment in which the
      inhibitory effect of TGF-beta is attenuated in association with greater uPA
      expression induced via beta1-integrin signaling. These findings suggest that the
      plasminogen-activation system involving uPA has the potential to contribute to
      airway wall remodeling in asthma.

PMID- 20693404
TI  - A subset of epithelial cells with CCSP promoter activity participates in alveolar
      development.
AB  - Alveolar formation is hallmarked by the transition of distal lung saccules into
      gas exchange units through the emergence of secondary crests and an exponential
      increase in surface area. Several cell types are involved in this complex
      process, including families of epithelial cells that differentiate into alveolar
      type I and II cells. Subsets of cells expressing Clara cell secretory protein
      (CCSP) have been identified in both lung and bone marrow compartments, and are
      described as a progenitor/stem cell pool involved in airway regeneration and
      alveolar homeostasis. Whether these cells also participate in alveolar formation
      during postnatal development remains unknown. Based on their regenerative
      capacity, we asked whether these cells participate in alveogenesis. We used a
      previously described transgenic mouse model (CCSP-tk) in which Ganciclovir
      exposure selectively depletes all cells with CCSP promoter activity through
      intracellular generation of a toxic metabolite of thymidine kinase. Our results
      showed that Ganciclovir treatment in newborn CCtk mice depleted this cell
      population in lung airways and bone marrow, and was associated with alveolar
      hypoplasia and respiratory failure. Hypoplastic lungs had fewer alveolar type I
      and II cells, with impaired secondary crest formation and decreased vascular
      endothelial growth factor expression in distal airways. These findings are
      consistent with a model in which a unique population of cells with CCSP promoter
      activity that expresses vascular endothelial growth factor participates in
      alveolar development.

PMID- 20693405
TI  - N-glycosylation augmentation of the cystic fibrosis epithelium improves
      Pseudomonas aeruginosa clearance.
AB  - Chronic lung colonization with Pseudomonas aeruginosa is anticipated in cystic
      fibrosis (CF). Abnormal terminal glycosylation has been implicated as a candidate
      for this condition. We previously reported a down-regulation of mannose-6
      phosphate isomerase (MPI) for core N-glycan production in the CFTR-defective
      human cell line (IB3). We found a 40% decrease in N-glycosylation of IB3 cells
      compared with CFTR-corrected human cell line (S9), along with a threefold-lower
      surface attachment of P. aeruginosa strain, PAO1. There was a twofold increase in
      intracellular bacteria in S9 cells compared with IB3 cells. After a 4-hour
      clearance period, intracellular bacteria in IB3 cells increased twofold.
      Comparatively, a twofold decrease in intracellular bacteria occurred in S9 cells.
      Gene augmentation in IB3 cells with hMPI or hCFTR reversed these IB3
      deficiencies. Mannose-6-phosphate can be produced from external mannose
      independent of MPI, and correction in the IB3 clearance deficiencies was observed
      when cultured in mannose-rich medium. An in vivo model for P. aeruginosa
      colonization in the upper airways revealed an increased bacterial burden in the
      trachea and oropharynx of nontherapeutic CF mice compared with mice treated
      either with an intratracheal delivery adeno-associated viral vector 5 expressing
      murine MPI, or a hypermannose water diet. Finally, a modest lung inflammatory
      response was observed in CF mice, and was partially corrected by both treatments.
      Augmenting N-glycosylation to attenuate colonization of P. aeruginosa in CF
      airways reveals a new therapeutic avenue for a hallmark disease condition in CF.

PMID- 20693406
TI  - The Epstein-Barr virus latent membrane protein 1 and transforming growth factor-
      beta1 synergistically induce epithelial--mesenchymal transition in lung
      epithelial cells.
AB  - The histopathology of idiopathic pulmonary fibrosis (IPF) includes the presence
      of myofibroblasts within so-called fibroblastic foci, and studies suggest that
      lung myofibroblasts may be derived from epithelial cells through epithelial-
      mesenchymal transition (EMT). Transforming growth factor (TGF)-beta1 is expressed
      and/or activated in fibrogenesis, and induces EMT in lung epithelial cells in a
      dose-dependent manner. A higher occurrence of Epstein-Barr virus (EBV) has been
      reported in the lung tissue of patients with IPF. EBV expresses latent membrane
      protein (LMP) 1 during the latent phase of infection, and may play a role in the
      pathogenesis of pulmonary fibrosis inasmuch as LMP-1 may act as a constitutively
      active TNF-alpha receptor. Our data show a remarkable increase in mesenchymal
      cell markers, along with a concurrent reduction in the expression of epithelial
      cell markers in lung epithelial cells cotreated with LMP-1, and very low doses of
      TGF-beta1. This effect was mirrored in lung epithelial cells infected with EBV
      expressing LMP1 and cotreated with TGF-beta1. LMP1 pro-EMT signaling was
      identified, and occurs primarily through the nuclear factor-kappaB pathway and
      secondarily through the extracellular signal--regulated kinase (ERK) pathway.
      Activation of the ERK pathway was shown to be critical for aspects of TGF-beta1
      induced EMT. LMP1 accentuates the TGF-beta1 activation of ERK. Together, these
      data demonstrate that the presence of EBV-LMP1 in lung epithelial cells
      synergizes with TGF-beta1 to induce EMT. Our in vitro data may help to explain
      the observation that patients with IPF demonstrating positive staining for LMP1
      in lung epithelial cells have a more rapid demise than patients in whom LMP1 is
      not detected.

PMID- 20693407
TI  - The leukocyte nuclear envelope proteome varies with cell activation and contains
      novel transmembrane proteins that affect genome architecture.
AB  - A favored hypothesis to explain the pathology underlying nuclear envelopathies is
      that mutations in nuclear envelope proteins alter genome/chromatin organization
      and thus gene expression. To identify nuclear envelope proteins that play roles
      in genome organization, we analyzed nuclear envelopes from resting and
      phytohemagglutinin-activated leukocytes because leukocytes have a particularly
      high density of peripheral chromatin that undergoes significant reorganization
      upon such activation. Thus, nuclear envelopes were isolated from leukocytes in
      the two states and analyzed by multidimensional protein identification technology
      using an approach that used expected contaminating membranes as subtractive
      fractions. A total of 3351 proteins were identified between both nuclear envelope
      data sets among which were 87 putative nuclear envelope transmembrane proteins
      (NETs) that were not identified in a previous proteomics analysis of liver
      nuclear envelopes. Nuclear envelope localization was confirmed for 11 new NETs
      using tagged fusion proteins and antibodies on spleen cryosections. 27% of the
      new proteins identified were unique to one or the other of the two leukocyte
      states. Differences in expression between activated and resting leukocytes were
      confirmed for some NETs by RT-PCR, and most of these proteins appear to only be
      expressed in certain types of blood cells. Several known proteins identified in
      both data sets have functions in chromatin organization and gene regulation. To
      test whether the novel NETs identified might include those that also regulate
      chromatin, nine were run through two screens for different chromatin effects. One
      screen found two NETs that can recruit a specific gene locus to the nuclear
      periphery, and the second found a different NET that promotes chromatin
      condensation. The variation in the protein milieu with pharmacological activation
      of the same cell population and consequences for gene regulation suggest that the
      nuclear envelope is a complex regulatory system with significant influences on
      genome organization.

PMID- 20693408
TI  - Growth of the C4 dicot Flaveria bidentis: photosynthetic acclimation to low light
      through shifts in leaf anatomy and biochemistry.
AB  - In C(4) plants, acclimation to growth at low irradiance by means of anatomical
      and biochemical changes to leaf tissue is considered to be limited by the need
      for a close interaction and coordination between bundle sheath and mesophyll
      cells. Here differences in relative growth rate (RGR), gas exchange, carbon
      isotope discrimination, photosynthetic enzyme activity, and leaf anatomy in the
      C(4) dicot Flaveria bidentis grown at a low (LI; 150 micromol quanta m(2) s(-1))
      and medium (MI; 500 micromol quanta m(2) s(-1)) irradiance and with a 12 h
      photoperiod over 36 d were examined. RGRs measured using a 3D non-destructive
      imaging technique were consistently higher in MI plants. Rates of CO(2)
      assimilation per leaf area measured at 1500 micromol quanta m(2) s(-1) were
      higher for MI than LI plants but did not differ on a mass basis. LI plants had
      lower Rubisco and phosphoenolpyruvate carboxylase activities and chlorophyll
      content on a leaf area basis. Bundle sheath leakiness of CO(2) (phi) calculated
      from real-time carbon isotope discrimination was similar for MI and LI plants at
      high irradiance. phi increased at lower irradiances, but more so in MI plants,
      reflecting acclimation to low growth irradiance. Leaf thickness and vein density
      were greater in MI plants, and mesophyll surface area exposed to intercellular
      airspace (S(m)) and bundle sheath surface area per unit leaf area (S(b)) measured
      from leaf cross-sections were also both significantly greater in MI compared with
      LI leaves. Both mesophyll and bundle sheath conductance to CO(2) diffusion were
      greater in MI compared with LI plants. Despite being a C(4) species, F. bidentis
      is very plastic with respect to growth irradiance.

PMID- 20693409
TI  - ZmMPK5 is required for the NADPH oxidase-mediated self-propagation of apoplastic
      H2O2 in brassinosteroid-induced antioxidant defence in leaves of maize.
AB  - Brassinosteroids (BRs) have been shown to induce hydrogen peroxide (H(2)O(2))
      accumulation, and BR-induced H(2)O(2) up-regulates antioxidant defence systems in
      plants. However, the mechanisms by which BR-induced H(2)O(2) regulates
      antioxidant defence systems in plants remain to be determined. In the present
      study, the role of ZmMPK5, a mitogen-activated protein kinase, in BR-induced
      anitioxidant defence and the relationship between the activation of ZmMPK5 and
      H(2)O(2) production in BR signalling were investigated in leaves of maize (Zea
      mays) plants. BR treatment activated ZmMPK5, induced apoplastic and chloroplastic
      H(2)O(2) accumulation, and enhanced the total activities of antioxidant enzymes.
      Such enhancements were blocked by pre-treatment with mitogen-activated protein
      kinase kinase (MAPKK) inhibitors and H(2)O(2) inhibitors or scavengers. Pre
      treatment with MAPKK inhibitors substantially arrested the BR-induced apoplastic
      H(2)O(2) production after 6 h of BR treatment, but did not affect the levels of
      apoplastic H(2)O(2) within 1 h of BR treatment. BR-induced gene expression of
      NADPH oxidase was also blocked by pre-treatment with MAPKK inhibitors and an
      apoplastic H(2)O(2) inhibitor or scavenger after 120 min of BR treatment, but was
      not affected within 30 min of BR treatment. These results suggest that the BR
      induced initial apoplastic H(2)O(2) production activates ZmMPK5, which is
      involved in self-propagation of apoplastic H(2)O(2) via regulation of NADPH
      oxidase gene expression in BR-induced antioxidant defence systems.

PMID- 20693410
TI  - Quantitative trait loci associated with longevity of lettuce seeds under
      conventional and controlled deterioration storage conditions.
AB  - Lettuce (Lactuca sativa L.) seeds have poor shelf life and exhibit
      thermoinhibition (fail to germinate) above ~25 degrees C. Seed priming
      (controlled hydration followed by drying) alleviates thermoinhibition by
      increasing the maximum germination temperature, but reduces lettuce seed
      longevity. Controlled deterioration (CD) or accelerated ageing storage conditions
      (i.e. elevated temperature and relative humidity) are used to study seed
      longevity and to predict potential seed lifetimes under conventional storage
      conditions. Seeds produced in 2002 and 2006 of a recombinant inbred line (RIL)
      population derived from a cross between L. sativa cv. Salinas*L. serriola
      accession UC96US23 were utilized to identify quantitative trait loci (QTLs)
      associated with seed longevity under CD and conventional storage conditions.
      Multiple longevity-associated QTLs were identified under both conventional and CD
      storage conditions for control (non-primed) and primed seeds. However, seed
      longevity was poorly correlated between the two storage conditions, suggesting
      that deterioration processes under CD conditions are not predictive of ageing in
      conventional storage conditions. Additionally, the same QTLs were not identified
      when RIL populations were grown in different years, indicating that lettuce seed
      longevity is strongly affected by production environment. Nonetheless, a major
      QTL on chromosome 4 [Seed longevity 4.1 (Slg4.1)] was responsible for almost 23%
      of the phenotypic variation in viability of the conventionally stored control
      seeds of the 2006 RIL population, with improved longevity conferred by the
      Salinas allele. QTL analyses may enable identification of mechanisms responsible
      for the sensitivity of primed seeds to CD conditions and breeding for improved
      seed longevity.

PMID- 20693411
TI  - Is the remobilization of S and N reserves for seed filling of winter oilseed rape
      modulated by sulphate restrictions occurring at different growth stages?
AB  - How the remobilization of S and N reserves can meet the needs of seeds of oilseed
      rape subject to limitation of S fertilization remains largely unclear. Thus, this
      survey aims to determine the incidence of sulphate restriction [low S (LS)]
      applied at bolting [growth stage (GS) 32], visible bud (GS 53), and start of pod
      filling (GS 70) on source-sink relationships for S and N, and on the dynamics of
      endogenous/exogenous S and N contributing to seed yield and quality. Sulphate
      restrictions applied at GS 32, GS 53, and GS 70 were annotated LS(32), LS(53),
      and LS(70). Long-term (34)SO(4)(2-) and (15)NO(3)(-) labelling was used to
      explore S and N partitioning at the whole-plant level. In LS(53), the sulphur
      remobilization efficiency (SRE) to seeds increased, but not enough to maintain
      seed quality. In LS(32), an early S remobilization from leaves provided S for
      root, stem, and pod growth, but the subsequent demand for seed development was
      not met adequately and the N utilization efficiency (NUtE) was reduced when
      compared with high S (HS). The highest SRE (65 +/- 1.2% of the remobilized S)
      associated with an efficient foliar S mobilization (with minimal residual S
      concentrations of 0.1-0.2% dry matter) was observed under LS(70) treatment, which
      did not affect yield components.

PMID- 20693413
TI  - Integration of Phot1, Phot2, and PhyB signalling in light-induced chloroplast
      movements.
AB  - In Arabidopsis thaliana, chloroplasts move towards the periclinal cell walls upon
      exposure to low blue light intensities and to anticlinal walls under high light.
      The regulation of these chloroplast movements involves members of both the
      phototropin and phytochrome families of photoreceptors. Examination of fluence
      rate response dependencies in phot1 and phot2 mutants revealed that although both
      photoreceptors are capable of inducing chloroplast accumulation under low-light
      conditions, the signals from these photoreceptors appear to be antagonistic.
      Chloroplast movements in wild-type plants were intermediate between those of the
      single phot mutants, consistent with each operating through separate signalling
      cascades. Mutants in phot2 showed transient chloroplast avoidance responses upon
      exposure to intense blue light, and slow but sustained chloroplast avoidance
      under intense white light, indicating that in the absence of phot2, phot1 is
      capable of generating both a low and a high-light response signal. Mutations in
      phytochrome B (phyB) caused an enhanced avoidance response at intermediate and
      high light intensities. Examination of phyB, phot1phyB, and phot2phyB mutants
      indicated that this enhancement is caused by PhyB inhibition of the high-light
      avoidance response in wild-type plants. In addition, our results suggest that the
      inhibition by PhyB is not exclusive to either of the phot1 or phot2 signalling
      pathways.

PMID- 20693412
TI  - Functional analysis of the structural domain of ARF proteins in rice (Oryza
      sativa L.).
AB  - Auxin response factors (ARFs) are key regulators of plant growth and development.
      Through interaction with auxin/indole acetic acid (Aux/IAA) proteins, they
      influence the expression of auxin response genes. An ARF gene family has been
      predicted in rice, but the functions of the individual structural domains of the
      OsARFs remain obscure. Bioinformatics was used to analyse the position of the DNA
      binding domain (DBD), middle region (MR), and C-terminal dimerization domain
      (CTD) of OsARFs, and experimentally confirmed the presence of a classical
      monopartite nuclear localization signal (NLS) in the DBD. The DBD was shown to
      contribute to nuclear localization of OsARF proteins in addition to its known DNA
      binding function. Interactions between 14 integrated OsARFs and 15 OsIAA proteins
      were tested using yeast two-hybrid assays. It was found that eight OsARF
      activators interacted with the 15 OsIAA proteins, while six OsARF repressors did
      not. The interactions between the MR+CTD or CTD of 10 OsARFs and 15 OsIAA
      proteins were also tested and the results were consistent with those of each
      intact OsARF, although some slight differences in interaction intensity were
      observed by alpha-galactosidase quantitative assays. The truncated CTD of OsARF11
      did not interact with any OsIAA, implying that the CTD is required for ARF-IAA
      dimerization, and that the MR influences the interaction intensity in yeast. A
      subset of the interactions in yeast were also observed in tobacco plants using
      firefly luciferase complementation imaging assays, indicating that these
      interactions are specific in plants, and might have a special role in the auxin
      signalling response. This study provides new insight into the structure of OsARF
      proteins and ARF-Aux/IAA interactions.

PMID- 20693414
TI  - Assessment of different on-farm measures of beef cattle temperament for use in
      genetic evaluation.
AB  - The aim of this study was to find a simple measure for calf temperament
      discrimination, which can be useful as a selection criterion for on-farm French
      beef cattle breeding schemes. Behavioral records were registered at an average
      age of 5 and 7 mo, respectively, for 1,282 and 1,440 Limousin calves born in 24
      French farms between August 2007 and April 2008. Measures were repeated for 810
      calves at the 2 ages. The test procedure consisted of individually restraining
      the calves in a chute, then exposing them to a stationary human situated in front
      of the chute for 10 s. For every calf and each period of the test, the number of
      rush movements and the total number of movements were scored by visual appraisal
      using a continuous scale ranging from 0 (no movements) to 60 (continuous
      movements). Initial scores were also transformed to categorical scores and
      analyzed. Genetic correlation across ages were very high for all the traits
      (above 0.84 +/- 0.20) suggesting that these traits are governed by the same pool
      of genes at the 2 ages. The corresponding phenotypic correlations were about 0.3
      for all the measures. Heritabilities were moderate for all measures (from 0.11 to
      0.31) with the total number of movements during weighing measured at 7 mo being
      the greatest. All the measures were highly correlated (from 0.73 +/- 0.26 to 0.99
      +/- 0.02). Genetic correlation across sexes was not statistically different from
      1. However, traits measured during weighing showed different genetic variance
      estimates for females and males. Similar results were obtained for the
      transformed categorical scores. According to these results, the total number of
      movements during weighing seems to be the most promising trait for on-farm
      genetic evaluation of French beef cattle temperament.

PMID- 20693415
TI  - Advance provision of emergency contraception for adolescents.
AB  - Emergency contraception is most effective at preventing unintended pregnancy when
      taken as early as possible following unprotected sexual intercourse. Advance
      provision of this medication supports more timely and effective use. In the midst
      of rising teen pregnancy rates, current policies often limit access to emergency
      contraception for adolescents. A literature search identified three recent
      experimental studies of advance provision for adolescents. This article reviews
      those studies and finds strong support for advance provision for adolescents.
      Usage of emergency contraception increased with advance provision and there was
      no increase in negative sexual behaviors or decrease in usage of other
      contraceptive forms. Implications of these findings for school nurses and school
      based health center staff are also discussed.

PMID- 20693416
TI  - Effect of hepatitis C virus infection on the mRNA expression of drug transporters
      and cytochrome p450 enzymes in chimeric mice with humanized liver.
AB  - The expression of drug transporters and metabolizing enzymes is a primary
      determinant of drug disposition. Chimeric mice with humanized liver, including
      PXB mice, are an available model that is permissive to the in vivo infection of
      hepatitis C virus (HCV), thus being a promising tool for investigational studies
      in development of new antiviral molecules. To investigate the potential of HCV
      infection to alter the pharmacokinetics of small molecule antiviral therapeutic
      agents in PXB mice, we have comprehensively determined the mRNA expression
      profiles of human ATP-binding cassette (ABC) transporters, solute carrier (SLC)
      transporters, and cytochrome P450 (P450) enzymes in the livers of these mice
      under noninfected and HCV-infected conditions. Infection of PXB mice with HCV
      resulted in an increase in the mRNA expression levels of a series of interferon
      stimulated genes in the liver. For the majority of genes involved in drug
      disposition, minor differences in the mRNA expression of ABC and SLC transporters
      as well as P450s between the noninfected and HCV-infected groups were observed.
      The exceptions were statistically significantly higher expression of multidrug
      resistance-associated protein 4 and organic anion-transporting polypeptide 2B1
      and lower expression of organic cation transporter 1 and CYP2D6 in HCV-infected
      mice. Furthermore, the enzymatic activities of the major human P450s were, in
      general, comparable in the two experimental groups. These data suggest that the
      pharmacokinetic properties of small molecule antiviral therapies in HCV-infected
      PXB mice are likely to be similar to those in noninfected PXB mice. However,
      caution is needed in the translation of this relationship to HCV-infected
      patients as the PXB mouse model does not accurately reflect the pathology of
      patients with chronic HCV infection.

PMID- 20693417
TI  - Using open source computational tools for predicting human metabolic stability
      and additional absorption, distribution, metabolism, excretion, and toxicity
      properties.
AB  - Ligand-based computational models could be more readily shared between
      researchers and organizations if they were generated with open source molecular
      descriptors [e.g., chemistry development kit (CDK)] and modeling algorithms,
      because this would negate the requirement for proprietary commercial software. We
      initially evaluated open source descriptors and model building algorithms using a
      training set of approximately 50,000 molecules and a test set of approximately
      25,000 molecules with human liver microsomal metabolic stability data. A C5.0
      decision tree model demonstrated that CDK descriptors together with a set of
      Smiles Arbitrary Target Specification (SMARTS) keys had good statistics [kappa =
      0.43, sensitivity = 0.57, specificity = 0.91, and positive predicted value (PPV)
      = 0.64], equivalent to those of models built with commercial Molecular Operating
      Environment 2D (MOE2D) and the same set of SMARTS keys (kappa = 0.43, sensitivity
      = 0.58, specificity = 0.91, and PPV = 0.63). Extending the dataset to ~193,000
      molecules and generating a continuous model using Cubist with a combination of
      CDK and SMARTS keys or MOE2D and SMARTS keys confirmed this observation. When the
      continuous predictions and actual values were binned to get a categorical score
      we observed a similar kappa statistic (0.42). The same combination of descriptor
      set and modeling method was applied to passive permeability and P-glycoprotein
      efflux data with similar model testing statistics. In summary, open source tools
      demonstrated predictive results comparable to those of commercial software with
      attendant cost savings. We discuss the advantages and disadvantages of open
      source descriptors and the opportunity for their use as a tool for organizations
      to share data precompetitively, avoiding repetition and assisting drug discovery.

PMID- 20693418
TI  - On the abundance of zinc in the evolutionarily old protein domains.

PMID- 20693420
TI  - N-ethyl-N-nitrosourea-induced mutation in ubiquitin-specific peptidase 18 causes
      hyperactivation of IFN-alphabeta signaling and suppresses STAT4-induced IFN-gamma
      production, resulting in increased susceptibility to Salmonella typhimurium.
AB  - To deepen our knowledge of the natural host response to pathogens, our team
      undertook an in vivo screen of mutagenized 129S1 mice with Salmonella
      Typhimurium. One mutation affecting Salmonella susceptibility was mapped to a
      region of 1.3 Mb on chromosome 6 that contains 15 protein-coding genes. A
      missense mutation was identified in the Usp18 (ubiquitin-specific peptidase 18)
      gene. This mutation results in an increased inflammatory response (IL-6, type 1
      IFN) to Salmonella and LPS challenge while paradoxically reducing IFN-gamma
      production during bacterial infection. Increased STAT1 phosphorylation correlated
      with impaired STAT4 phosphorylation, resulting in overwhelming IL-6 secretion but
      reduced IFN-gamma production during infection. The reduced IFN-gamma levels,
      along with the increased inflammation, rationalize the S. Typhimurium
      susceptibility in terms of increased bacterial load in target organs and cytokine
      induced septic shock and death.

PMID- 20693421
TI  - IL-33 exacerbates eosinophil-mediated airway inflammation.
AB  - IL-33 has emerged as an important mediator in the immunopathogenesis of allergy
      and asthma. However, the role of IL-33 in eosinophil-mediated inflammation has
      not been fully explored. In this article, we report that IL-33 directly
      stimulates eosinophil differentiation from CD117(+) progenitors in an IL-5
      dependent manner. Although resting eosinophils expressed moderate levels of the
      IL-33R alpha-chain (ST2L), eosinophils that accumulated in the airways of mice
      with OVA-induced asthma expressed increased amounts of ST2L. In vitro, IL-33 and
      GM-CSF are potent inducers of ST2L expression on eosinophils, and IL-33 induced
      the production of IL-13, CCL17, and TGF-beta by eosinophils. In adoptive-transfer
      experiments, IL-33 exacerbated eosinophil-mediated airway inflammation by
      increasing the levels of eosinophils, macrophages, lymphocytes, IL-13, TGF-beta,
      CCL3, CCL17, and CCL24 in the lungs. IL-33 also enhanced the eosinophil-mediated
      differentiation of airway macrophages toward the alternatively activated
      macrophage phenotype in an IL-13-dependent manner. Taken together, this study
      demonstrates that the IL-33/ST2 signaling pathway activates airway eosinophils
      that exacerbate airway inflammation in an autocrine and paracrine manner.

PMID- 20693422
TI  - B and T lymphocyte attenuator is highly expressed on CMV-specific T cells during
      infection and regulates their function.
AB  - B and T lymphocyte attenuator (BTLA), like its relative programmed cell death-1
      (PD-1), is a receptor that negatively regulates murine T cell activation.
      However, its expression and function on human T cells is currently unknown. We
      report in this study on the expression of BTLA in human T cell subsets as well as
      its regulation on virus-specific T cells during primary human CMV infection. BTLA
      is expressed on human CD4(+) T cells during different stages of differentiation,
      whereas on CD8(+) T cells, it is found on naive T cells and is progressively
      downregulated in memory and differentiated effector-type cells. During primary
      CMV infection, BTLA was highly induced on CMV-specific CD8(+) T cells immediately
      following their differentiation from naive cells. After control of CMV infection,
      BTLA expression went down on memory CD8(+) cells. Engagement of BTLA by mAbs
      blocked CD3/CD28-mediated T cell proliferation and Th1 and Th2 cytokine
      secretion. Finally, in vitro blockade of the BTLA pathway augmented, as efficient
      as anti-PD-1 mAbs, allogeneic as well as CMV-specific CD8(+) T cell
      proliferation. Thus, our results suggest that, like PD-1, BTLA provides a
      potential target for enhancing the functional capacity of CTLs in viral
      infections.

PMID- 20693423
TI  - Netrin-1 regulates Th1/Th2/Th17 cytokine production and inflammation through
      UNC5B receptor and protects kidney against ischemia-reperfusion injury.
AB  - Overwhelming evidence suggests that ischemia-reperfusion injury of the kidney is
      an inflammatory disease mediated by innate and adoptive immune systems. The
      neuronal guidance molecule netrin-1 was shown to modulate inflammatory responses.
      Given that ischemic kidney is particularly prone to reperfusion-elicited
      inflammation, we sought to determine the function of netrin-1 and its receptor
      UNC5B in ischemia-reperfusion-induced inflammation. Renal ischemia-reperfusion
      caused a rapid decrease in serum netrin-1 levels. Administration of recombinant
      netrin-1 before or after renal ischemia-reperfusion reduced kidney injury,
      apoptosis, monocyte and neutrophil infiltration, and cytokine (IL-6, IL-1beta,
      and TNF-alpha) and chemokine (MCP-1, macrophage-derived cytokine, monokine
      induced IFN-gamma, keratinocyte-derived chemokine, and chemokine with 6
      cysteines) production. Analysis for different netrin-1 receptors on leukocytes
      showed very high expression of UNC5B but not UNC5C, UNC5D, neogenin, or deleted
      in colorectal cancer. Expression of UNC5A was low. Neutralization of UNC5B
      receptor reduced netrin-1-mediated protection against renal ischemia-reperfusion
      injury, and it increased monocyte and neutrophil infiltration, as well as serum
      and renal cytokine and chemokine production, with increased kidney injury and
      renal tubular cell apoptosis. Finally, investigation into netrin-1's effect on
      CD4 T cell stimulation showed suppression of Th1/Th2/Th17 cytokine (IL-2, IL-6,
      IL-10, IL-13, IL-17, IFN-gamma, IL-4, and TNF-alpha) production in vitro. Our
      studies demonstrate that netrin-1 acting through UNC5B receptor reduces renal
      ischemia-reperfusion injury and its associated renal inflammation.

PMID- 20693424
TI  - The absence of IDO upregulates type I IFN production, resulting in suppression of
      viral replication in the retrovirus-infected mouse.
AB  - Indoleamine 2,3-dioxygenase, the L-tryptophan-degrading enzyme, plays a key role
      in the powerful immunomodulatory effects on several different types of cells.
      Because modulation of IDO activities after viral infection may have great impact
      on disease progression, we investigated the role of IDO following infection with
      LP-BM5 murine leukemia virus. We found suppressed BM5 provirus copies and
      increased type I IFNs in the spleen from IDO knockout (IDO(-/-)) and 1-methyl-D-L
      tryptophan-treated mice compared with those from wild-type (WT) mice.
      Additionally, the number of plasmacytoid dendritic cells in IDO(-/-) mice was
      higher in the former than in the WT mice. In addition, neutralization of type I
      IFNs in IDO(-/-) mice resulted in an increase in LP-BM5 viral replication.
      Moreover, the survival rate of IDO(-/-) mice or 1-methyl-D-L-tryptophan-treated
      mice infected with LP-BM5 alone or with both Toxoplasma gondii and LP-BM5 was
      clearly greater than the survival rate of WT mice. To our knowledge, the present
      study is the first report to observe suppressed virus replication with
      upregulated type I IFN in IDO(-/-) mice, suggesting that modulation of the IDO
      pathway may be an effective strategy for treatment of virus infection.

PMID- 20693425
TI  - Cutting edge: association with I kappa B kinase beta regulates the subcellular
      localization of Homer3.
AB  - The signaling and adaptor protein Homer3 plays a role in controlling immune
      homeostasis and self-reactivity. Homer3 is recruited to the immune synapse (IS)
      following TCR ligation, although the mechanisms regulating this subcellular
      localization are unknown. We show that Homer3 specifically associates with a
      novel ubiquitin-like domain in the IkappaB kinase (IKK) beta subunit of the IKK
      complex. Homer3 associates with IKKbeta in T cells and colocalizes with the IKK
      complex at the IS. However, Homer3 is not required for IKK activation, as NF
      kappaB signaling is intact in Homer3-deficient T cells. Instead, the IKK complex
      recruits Homer3 to the IS following TCR engagement, and we present evidence that
      this association regulates actin dynamics in T cells. These findings identify a
      novel interaction between two major signaling proteins and reveal an unexpected
      NF-kappaB-independent function for the IKK complex in regulating the subcellular
      localization of Homer3.

PMID- 20693426
TI  - Secondary immunization generates clonally related antigen-specific plasma cells
      and memory B cells.
AB  - Rechallenge with T cell-dependent Ags induces memory B cells to re-enter germinal
      centers (GCs) and undergo further expansion and differentiation into plasma cells
      (PCs) and secondary memory B cells. It is currently not known whether the
      expanded population of memory B cells and PCs generated in secondary GCs are
      clonally related, nor has the extent of proliferation and somatic hypermutation
      of their precursors been delineated. In this study, after secondary tetanus
      toxoid (TT) immunization, TT-specific PCs increased 17- to 80-fold on days 6-7,
      whereas TT-specific memory B cells peaked (delayed) on day 14 with a 2- to 22
      fold increase. Molecular analyses of V(H)DJ(H) rearrangements of individual cells
      revealed no major differences of gene usage and CDR3 length between TT-specific
      PCs and memory B cells, and both contained extensive evidence of somatic
      hypermutation with a pattern consistent with GC reactions. This analysis
      identified clonally related TT-specific memory B cells and PCs. Within clusters
      of clonally related cells, sequences shared a number of mutations but also could
      contain additional base pair changes. The data indicate that although following
      secondary immunization PCs can derive from memory B cells without further somatic
      hypermutation, in some circumstances, likely within GC reactions, asymmetric
      mutation can occur. These results suggest that after the fate decision to
      differentiate into secondary memory B cells or PCs, some committed precursors
      continue to proliferate and mutate their V(H) genes.

PMID- 20693427
TI  - Overcoming fixation. Creative problem solving and retrieval-induced forgetting.

PMID- 20693428
TI  - Evidence of dysregulation of dendritic cells in primary HIV infection.
AB  - Myeloid and plasmacytoid dendritic cells (DCs) are important mediators of both
      innate and adaptive immunity against pathogens such as HIV. During the course of
      HIV infection, blood DC numbers fall substantially. In the present study, we
      sought to determine how early in HIV infection the reduction occurs and whether
      the remaining DC subsets maintain functional capacity. We find that both myeloid
      DC and plasmacytoid DC levels decline very early during acute HIV infection.
      Despite the initial reduction in numbers, those DCs that remain in circulation
      retain their function and are able to stimulate allogeneic T-cell responses, and
      up-regulate maturation markers plus produce cytokines/chemokines in response to
      stimulation with TLR7/8 agonists. Notably, DCs from HIV-infected subjects
      produced significantly higher levels of cytokines/chemokines in response to
      stimulation with TLR7/8 agonists than DCs from uninfected controls. Further
      examination of gene expression profiles indicated in vivo activation, either
      directly or indirectly, of DCs during HIV infection. Taken together, our data
      demonstrate that despite the reduction in circulating DC numbers, those that
      remain in the blood display hyperfunctionality and implicates a possible role for
      DCs in promoting chronic immune activation.

PMID- 20693429
TI  - Randomized study of induction therapy comparing standard-dose idarubicin with
      high-dose daunorubicin in adult patients with previously untreated acute myeloid
      leukemia: the JALSG AML201 Study.
AB  - We conducted a multi-institutional randomized study to determine whether high
      dose daunorubicin would be as effective as standard-dose idarubicin in remission
      induction therapy for newly diagnosed adult patients younger than 65 years of age
      with acute myeloid leukemia. Of 1064 patients registered, 1057 were evaluable.
      They were randomly assigned to receive either daunorubicin (50 mg/m(2) daily for
      5 days) or idarubicin (12 mg/m(2) daily for 3 days) in combination with 100
      mg/m(2) of cytarabine by continuous infusion daily for 7 days as induction
      therapy. Complete remission was achieved in 407 (77.5%) of 525 patients in the
      daunorubicin group and 416 (78.2%) of 532 in the idarubicin group (P = .79).
      Patients achieving complete remission received intensive postremission therapy
      that consisted of either 3 courses of high-dose cytarabine or 4 courses of
      standard-dose therapy. Overall survival rates at 5 years were 48% for the
      daunorubicin group and 48% for the idarubicin group (P = .54), and relapse-free
      survival rates at 5 years were 41% and 41% (P = .97), respectively. Thus, high
      dose daunorubicin and standard-dose idarubicin were equally effective for the
      treatment of adult acute myeloid leukemia, achieving a high rate of complete
      remission and good long-term efficacy. This study is registered at
      http://www.umin.ac.jp/ctrj/ as C000000157.

PMID- 20693430
TI  - Next-generation sequencing of the TET2 gene in 355 MDS and CMML patients reveals
      low-abundance mutant clones with early origins, but indicates no definite
      prognostic value.
AB  - Mutations in the TET2 gene are frequent in myeloid disease, although their
      biologic and prognostic significance remains unclear. We analyzed 355 patients
      with myelodysplastic syndromes using "next-generation" sequencing for TET2
      aberrations, 91 of whom were also subjected to single-nucleotide polymorphism 6.0
      array karyotyping. Seventy-one TET2 mutations, with a relative mutation abundance
      (RMA) >= 10%, were identified in 39 of 320 (12%) myelodysplastic syndrome and 16
      of 35 (46%) chronic myelomonocytic leukemia patients (P < .001). Interestingly, 4
      patients had multiple mutations likely to exist as independent clones or on
      alternate alleles, suggestive of clonal evolution. "Deeper" sequencing of 96
      patient samples identified 4 additional mutations (RMA, 3%-6.3%). Importantly,
      TET2 mutant clones were also found in T cells, in addition to CD34(+) and total
      bone marrow cells (23.5%, 38.5%, and 43% RMA, respectively). Only 20% of the TET2
      mutated patients showed loss of heterozygosity at the TET2 locus. There was no
      difference in the frequency of genome-wide aberrations, TET2 expression, or the
      JAK2V617F 46/1 haplotype between TET2-mutated and nonmutated patients. There was
      no significant prognostic association between TET2 mutations and World Health
      Organization subtypes, International Prognostic Scoring System score, cytogenetic
      status, or transformation to acute myeloid leukemia. On multivariate analysis,
      age (> 50 years) was associated with a higher incidence of TET2 mutation (P =
      .02).

PMID- 20693432
TI  - Distinct clinical and biological features of de novo acute myeloid leukemia with
      additional sex comb-like 1 (ASXL1) mutations.
AB  - Mutations in the additional sex comb-like 1 (ASXL1) gene were recently shown in
      various myeloid malignancies, but they have not been comprehensively investigated
      in acute myeloid leukemia (AML). In this study, we analyzed ASXL1 mutations in
      exon 12 in 501 adults with de novo AML. ASXL1 mutations were detected in 54
      patients (10.8%), 8.9% among those with normal karyotype and 12.9% among those
      with abnormal cytogenetics. The mutation was closely associated with older age,
      male sex, isolated trisomy 8, RUNX1 mutation, and expression of human leukocyte
      antigen-DR and CD34, but inversely associated with t(15;17), complex
      cytogenetics, FLT3-internal tandem duplication, NPM1 mutations, WT1 mutations,
      and expression of CD33 and CD15. Patients with ASXL1 mutations had a shorter
      overall survival than patients without, but the mutation was not an independent
      adverse prognostic factor in multivariate analysis. Sequential analyses showed
      that the original ASXL1 mutations were lost at relapse and/or refractory status
      in 2 of the 6 relapsed ASXL1-mutated patients studied, whereas 2 of the 109 ASXL1
      wild patients acquired a novel ASXL1 mutation at relapse. In conclusion, AML
      bearing ASXL1 mutations showed distinct clinical and biological features. The
      ASXL1 mutation status can change during disease evolution in a few patients.

PMID- 20693433
TI  - VE-cadherin expression allows identification of a new class of hematopoietic stem
      cells within human embryonic liver.
AB  - Edification of the human hematopoietic system during development is characterized
      by the production of waves of hematopoietic cells separated in time, formed in
      distinct embryonic sites (ie, yolk sac, truncal arteries including the aorta, and
      placenta). The embryonic liver is a major hematopoietic organ wherein
      hematopoietic stem cells (HSCs) expand, and the future, adult-type, hematopoietic
      cell hierarchy becomes established. We report herein the identification of a new,
      transient, and rare cell population in the human embryonic liver, which
      coexpresses VE-cadherin, an endothelial marker, CD45, a pan-hematopoietic marker,
      and CD34, a common endothelial and hematopoietic marker. This population displays
      an outstanding self-renewal, proliferation, and differentiation potential, as
      detected by in vitro and in vivo hematopoietic assays compared with its VE
      cadherin negative counterpart. Based on VE-cadherin expression, our data
      demonstrate the existence of 2 phenotypically and functionally separable
      populations of multipotent HSCs in the human embryo, the VE-cadherin(+) one being
      more primitive than the VE-cadherin(-) one, and shed a new light on the
      hierarchical organization of the embryonic liver HSC compartment.

PMID- 20693431
TI  - PPARgamma activation normalizes resolution of acute sterile inflammation in
      murine chronic granulomatous disease.
AB  - Absence of a functional nicotinamide adenine dinucleotide phosphate (NADPH)
      oxidase predisposes chronic granulomatous disease (CGD) patients to infection,
      and also to unexplained, exaggerated inflammation. The impaired recognition and
      removal (efferocytosis) of apoptotic neutrophils by CGD macrophages may
      contribute to this effect. We hypothesized that peroxisome proliferator-activated
      receptor gamma (PPARgamma) activation during CGD inflammation is deficient,
      leading to altered macrophage programming and decreased efferocytosis, and that
      PPARgamma agonism would enhance resolution. using the gp91(phox-/-) murine model
      of X-linked CGD in a well-characterized model of sterile, zymosan-induced
      peritonitis, it was demonstrated that PPARgamma expression and activation in CGD
      macrophages were significantly deficient at baseline, and acquisition was delayed
      over the course of inflammation relative to that of wild-type. Efferocytosis by
      macrophages reflected PPARgamma activation during peritonitis and was impaired in
      CGD mice (versus wild-type), leading to accumulation of apoptotic neutrophils.
      Importantly, provision of the PPARgamma agonist, pioglitazone, either
      prophylactically or during inflammation, significantly enhanced macrophage
      PPARgamma-mediated programming and efferocytosis, reduced accumulation of
      apoptotic neutrophils, and normalized the course of peritonitis in CGD mice. As
      such, PPARgamma may be a therapeutic target for CGD, and possibly other
      inflammatory conditions where aberrant macrophage programming and impaired
      efferocytosis delay resolution of inflammation.

PMID- 20693434
TI  - Should we publish pilot/feasibility studies?

PMID- 20693435
TI  - Embrace change and make way for the future.

PMID- 20693439
TI  - Alternate site testing for hemoglobin A1C in children with diabetes.
AB  - PURPOSE: Alternate site testing is appropriate for blood glucose monitoring in
      euglycemic states, but use of alternate sites for collection of hemoglobin A1C
      has not been studied. The purpose of this study was to determine whether A1C
      results obtained from palm or forearm samples are equivalent to A1C results
      obtained from fingertip samples in a pediatric population. The secondary purposes
      were to determine whether there were differences in the perceived level of site
      pain and if there was a site preference. METHODS: Eighty-four children aged 5 to
      20 years with type 1 or type 2 diabetes were randomly assigned to either
      fingertip and palm (N = 41) or fingertip and forearm (N = 40) groups. A1C samples
      were obtained in random order with 1 sample immediately following the other.
      RESULTS: Intraclass correlation coefficients were 0.99 for fingertip and palm,
      and 0.98 for fingertip and forearm. Paired t tests showed no differences between
      either set of values. Bland-Altman bias was minimal: -0.01% (95% confidence
      interval [CI], -0.07% to 0.05%) for the fingertip/palm comparison and 0.0% (95%
      CI, -0.001 to 0.001) for the fingertip/forearm comparison. The fingertip was
      preferred by 54.8%, the forearm by 25%, and the palm by 20.2% of the children.
      Pain ratings were lowest for the forearm followed by the fingertip and palm.
      CONCLUSIONS: Blood samples for measurement of A1C are clinically equivalent from
      the fingertip and palm or fingertip and forearm. Perceived pain was lowest when
      samples were obtained from the forearm. Just over half (54.8%) of the children
      preferred the fingertip.

PMID- 20693440
TI  - Endopeptidase activities of botulinum neurotoxin type B complex, holotoxin, and
      light chain.
AB  - Botulinum neurotoxin (BoNT) serotype B (BoNT/B) is one of the serotypes of BoNT
      that causes deadly human botulism, though it is used clinically for treatment of
      many neuromuscular diseases. BoNT/B is produced by Clostridium botulinum, and it
      is secreted along with a group of neurotoxin-associated proteins (NAPs) in the
      form of a BoNT/B complex. The complex dissociates into a 150-kDa holotoxin and
      NAPs at alkaline pHs. The 150-kDa BoNT/B holotoxin can be nicked to produce a 50
      kDa domain referred to as the light chain (LC) and a 100-kDa heavy chain, with
      the former possessing a unique endopeptidase activity. The two chains remain
      linked through a disulfide bond that can be reduced to separate the two chains.
      The endopeptidase activity is present in all three forms of the toxin (complex,
      purified BoNT/B holotoxin, and separated light chain), which are used by
      different researchers to develop detection methods and screen for inhibitors. In
      this research, the endopeptidase activities of the three forms, for the first
      time, were compared under the same conditions. The results show that enzyme
      activities of the three forms differ significantly and are largely dependent on
      nicking and disulfide reduction conditions. Under the conditions used, LC had the
      highest level of activity, and the complex had the lowest. The activity was
      enhanced by nicking of BoNT/B holotoxin and was enhanced even more by
      dithiothreitol (DTT) reduction after nicking. This information is useful for
      understanding the properties of BoNT endopeptidases and for comparing the
      efficacies of different inhibitors when they are tested with different forms of
      BoNT endopeptidase.

PMID- 20693441
TI  - Development of pyrF-based genetic system for targeted gene deletion in
      Clostridium thermocellum and creation of a pta mutant.
AB  - We report development of a genetic system for making targeted gene knockouts in
      Clostridium thermocellum, a thermophilic anaerobic bacterium that rapidly
      solubilizes cellulose. A toxic uracil analog, 5-fluoroorotic acid (5-FOA), was
      used to select for deletion of the pyrF gene. The DeltapyrF strain is a uracil
      auxotroph that could be restored to a prototroph via ectopic expression of pyrF
      from a plasmid, providing a positive genetic selection. Furthermore, 5-FOA was
      used to select against plasmid-expressed pyrF, creating a negative selection for
      plasmid loss. This technology was used to delete a gene involved in organic acid
      production, namely pta, which encodes the enzyme phosphotransacetylase. The C.
      thermocellum Deltapta strain did not produce acetate. These results are the first
      examples of targeted homologous recombination and metabolic engineering in C.
      thermocellum, a microbe that holds an exciting and promising future in the
      biofuel industry and development of sustainable energy resources.

PMID- 20693442
TI  - Lactobacillus strain ecology and persistence within broiler chickens fed
      different diets: identification of persistent strains.
AB  - Lactobacilli are autochthonous residents in the chicken gastrointestinal tract,
      where they may potentially be used as probiotics, competitive exclusion agents,
      or delivery vehicles. The aim of this study was to use an in vivo model to
      investigate the effect of diet and competing lactic acid bacteria on the
      colonization of inoculated Lactobacillus strains, with the goal of identifying
      strains which can consistently colonize or persist for an extended period of
      several weeks. Chicken-derived Lactobacillus strains were genetically marked with
      rifampin resistance and administered on day 0 to chickens fed either a normal
      commercial diet or a specially formulated high-protein diet. Chickens fed the
      high-protein diet were also coinoculated with two different mixes of additional
      lactic acid bacteria. Enterobacterial repetitive intergenic consensus sequence
      based PCR (ERIC-PCR) was used to identify rifampin-resistant isolates recovered
      from chickens. Three strains, belonging to the species Lactobacillus agilis,
      Lactobacillus crispatus, and Lactobacillus vaginalis, were commonly reisolated
      from the chickens on both diets at days 21 and 42. The ability of these strains
      to persist was confirmed in a second chicken trial. All three strains persisted
      throughout the production period in the chickens fed a commercial diet, while
      only the L. agilis and L. vaginalis strains persisted in the chickens fed the
      high-protein diet. In both in vivo trials, competing lactic acid bacteria
      modified representation of the strains recovered, with all three stains capable
      of competing in the presence of one or both mixes of coinoculated strains. The in
      vivo model successfully identified three persistent strains that will be
      characterized further.

PMID- 20693443
TI  - Anaerobic biotransformation of high concentrations of chloroform by an enrichment
      culture and two bacterial isolates.
AB  - A fermentative enrichment culture (designated DHM-1) was developed that is
      capable of cometabolically biotransforming high concentrations of chloroform (CF)
      to nontoxic end products. Two Pantoea spp. were isolated from DHM-1 that also
      possess this dechlorination capability. Following acclimation to increasing
      levels of CF, corn syrup-grown DHM-1 was able to transform over 500 mg/liter CF
      in the presence of vitamin B(12) (approximately 3% of CF on a molar basis) at a
      rate as high as 22 mg/liter/day in a mineral salts medium. CO, CO(2), and organic
      acids were the predominant biodegradation products, suggesting that hydrolytic
      reactions predominate during CF transformation. DHM-1 was capable of growing on
      corn syrup in the presence of high concentrations of CF (as may be present near
      contaminant source zones in groundwater), which makes it a promising culture for
      bioaugmentation. Strains DHM-1B and DHM-1T transform CF at rates similar to that
      of the DHM-1 enrichment culture. The ability of these strains to grow in the
      presence of high concentrations of CF appears to be related to alteration of
      membrane fluidity or homeoviscous and homeophasic adaptation.

PMID- 20693444
TI  - Influence of the diversity of bacterial isolates from drinking water on
      resistance of biofilms to disinfection.
AB  - Single- and multispecies biofilms formed by six drinking water-isolated bacterial
      species were used to assess their susceptibilities to sodium hypochlorite (SHC).
      In general, multispecies biofilms were more resistant to inactivation and removal
      than single biofilms. Total biofilm inactivation was achieved only for
      Acinetobacter calcoaceticus single-species biofilms and for those multispecies
      biofilms without A. calcoaceticus. Biofilms with all bacteria had the highest
      resistance to SHC, while those without A. calcoaceticus were the most
      susceptible. A. calcoaceticus formed single biofilms susceptible to SHC; however,
      its presence in multispecies biofilms increased their resistance to disinfection.

PMID- 20693445
TI  - Effect of pesticide inoculation, duration of composting, and degradation time on
      the content of compost fatty acids, quantified using two methods.
AB  - Compost biobeds can promote biodegradation of pesticides. The microbial community
      structure changes during the composting process, and simple methods can
      potentially be used to follow these changes. In this study the microbial
      identification (MIDI) and ester-linked (EL) procedures were used to determine the
      composition of fatty acid methyl esters (FAMEs) in composts aged 3 and 12 months,
      inoculated with 3 recalcitrant pesticides (azoxystrobin, chlorotoluron, and
      epoxyconazole and a coapplication of all three) after 0, 56, and 125 days of
      degradation. Pesticide persistence was high, and after 125 days the residue was
      22 to 70% of the applied amount depending mostly on the composting age. Seventy
      one FAMEs belonging to nine groups were detected. The EL method provided three
      times as many detections as did the MIDI method and was more sensitive for all
      FAME groups except alcohol. Thirty-six and five FAMEs were unique to the EL and
      MIDI methods, respectively. The extraction method was of importance. The EL
      method provided a higher number of detections for 57 FAMEs, and the MIDI method
      provided a higher number for 9 FAMEs, while the two methods were equal for 5
      FAMEs; thus, the EL method provided a more uniform overall FAME profile. Effects
      of the other factors were not always clear. Inoculation with pesticide did not
      influence the FAME profile with the MIDI method, while it influenced cyclopropane
      and monounsaturated content with the EL method. Composting age and degradation
      time had an effect on some groups of FAMEs, and this effect was greater with the
      EL method. The use of some FAMEs as biomarkers to follow microbial community
      succession was likely influenced by the type of compost and other factors.

PMID- 20693446
TI  - Prevalence of ColE1-like plasmids and kanamycin resistance genes in Salmonella
      enterica serovars.
AB  - Multi-antimicrobial-resistant Salmonella enterica strains frequently carry
      resistance genes on plasmids. Recent studies focus heavily on large conjugative
      plasmids, and the role that small plasmids play in resistance gene transfer is
      largely unknown. To expand our previous studies in assessing the prevalence of
      the isolates harboring ColE1-like plasmids carrying the aph gene responsible for
      kanamycin resistance (Kan(r)) phenotypes, 102 Kan(r) Salmonella isolates
      collected through the National Antimicrobial Resistance Monitoring System (NARMS)
      in 2005 were screened by PCR using ColE1 primer sets. Thirty isolates were found
      to be positive for ColE1-like replicon. Plasmids from 23 isolates were able to
      propagate in Escherichia coli and were subjected to further characterization.
      Restriction mapping revealed three major plasmid groups found in three or more
      isolates, with each group consisting of two to three subtypes. The aph genes from
      the Kan(r) Salmonella isolates were amplified by PCR, sequenced, and showed four
      different aph(3')-I genes. The distribution of the ColE1 plasmid groups in
      association with the aph gene, Salmonella serovar, and isolate source
      demonstrated a strong linkage of the plasmid with S. enterica serovar Typhimurium
      DT104. Due to their high copy number and mobility, the ColE1-like plasmids may
      play a critical role in transmission of antibiotic resistance genes among enteric
      pathogens, and these findings warrant a close monitoring of this plasmid
      incompatibility group.

PMID- 20693447
TI  - Exploring mechanisms of resistance to respiratory inhibitors in field strains of
      Botrytis cinerea, the causal agent of gray mold.
AB  - Respiratory inhibitors are among the fungicides most widely used for disease
      control on crops. Most are strobilurins and carboxamides, inhibiting the
      cytochrome b of mitochondrial complex III and the succinate dehydrogenase of
      mitochondrial complex II, respectively. A few years after the approval of these
      inhibitors for use on grapevines, field isolates of Botrytis cinerea, the causal
      agent of gray mold, resistant to one or both of these classes of fungicide were
      recovered in France and Germany. However, little was known about the mechanisms
      underlying this resistance in field populations of this fungus. Such knowledge
      could facilitate resistance risk assessment. The aim of this study was to
      investigate the mechanisms of resistance occurring in B. cinerea populations.
      Highly specific resistance to strobilurins was correlated with a single mutation
      of the cytb target gene. Changes in its intronic structure may also have occurred
      due to an evolutionary process controlling selection for resistance. Specific
      resistance to carboxamides was identified for six phenotypes, with various
      patterns of resistance levels and cross-resistance. Several mutations specific to
      B. cinerea were identified within the sdhB and sdhD genes encoding the iron
      sulfur protein and an anchor protein of the succinate dehydrogenase complex.
      Another as-yet-uncharacterized mechanism of resistance was also recorded. In
      addition to target site resistance mechanisms, multidrug resistance, linked to
      the overexpression of membrane transporters, was identified in strains with low
      to moderate resistance to several respiratory inhibitors. This diversity of
      resistance mechanisms makes resistance management difficult and must be taken
      into account when developing strategies for Botrytis control.

PMID- 20693448
TI  - Heterologous expression and extracellular secretion of cellulolytic enzymes by
      Zymomonas mobilis.
AB  - Development of the strategy known as consolidated bioprocessing (CBP) involves
      the use of a single microorganism to convert pretreated lignocellulosic biomass
      to ethanol through the simultaneous production of saccharolytic enzymes and
      fermentation of the liberated monomeric sugars. In this report, the initial steps
      toward achieving this goal in the fermentation host Zymomonas mobilis were
      investigated by expressing heterologous cellulases and subsequently examining the
      potential to secrete these cellulases extracellularly. Numerous strains of Z.
      mobilis were found to possess endogenous extracellular activities against
      carboxymethyl cellulose, suggesting that this microorganism may harbor a
      favorable environment for the production of additional cellulolytic enzymes. The
      heterologous expression of two cellulolytic enzymes, E1 and GH12 from
      Acidothermus cellulolyticus, was examined. Both proteins were successfully
      expressed as soluble, active enzymes in Z. mobilis although to different levels.
      While the E1 enzyme was less abundantly expressed, the GH12 enzyme comprised as
      much as 4.6% of the total cell protein. Additionally, fusing predicted secretion
      signals native to Z. mobilis to the N termini of E1 and GH12 was found to direct
      the extracellular secretion of significant levels of active E1 and GH12 enzymes.
      The subcellular localization of the intracellular pools of cellulases revealed
      that a significant portion of both the E1 and GH12 secretion constructs resided
      in the periplasmic space. Our results strongly suggest that Z. mobilis is capable
      of supporting the expression and secretion of high levels of cellulases relevant
      to biofuel production, thereby serving as a foundation for developing Z. mobilis
      into a CBP platform organism.

PMID- 20693450
TI  - Glutamate decarboxylase-mediated nisin resistance in Listeria monocytogenes.
AB  - Analysis of a complete set of glutamate decarboxylase (gad) mutants of Listeria
      monocytogenes strain LO28 (DeltagadD1, DeltagadDT1, DeltagadD2, DeltagadT2, and
      DeltagadD3 mutants) revealed that the DeltagadD1 mutant is impaired in its
      ability to tolerate exposure to both sublethal and lethal levels of the
      lantibiotic nisin. gadD1 is strain variable and is found only in approximately
      50% of L. monocytogenes strains. Growth and survival experiments revealed that
      possession of gadD1 correlates with a higher degree of tolerance to nisin.
      Significantly, a similar finding using a gadB mutant of L. lactis IL1403 implies
      that this may be a general phenomenon in Gram-positive bacteria. Our findings
      thus suggest that the specific inhibition of GAD activity or a reduction in the
      levels of free glutamate may prevent the growth of otherwise resistant GAD(+)
      bacteria in foods where low pH and/or nisin is used as a preservative.

PMID- 20693449
TI  - Boosting autofermentation rates and product yields with sodium stress cycling:
      application to production of renewable fuels by cyanobacteria.
AB  - Sodium concentration cycling was examined as a new strategy for redistributing
      carbon storage products and increasing autofermentative product yields following
      photosynthetic carbon fixation in the cyanobacterium Arthrospira (Spirulina)
      maxima. The salt-tolerant hypercarbonate strain CS-328 was grown in a medium
      containing 0.24 to 1.24 M sodium, resulting in increased biosynthesis of soluble
      carbohydrates to up to 50% of the dry weight at 1.24 M sodium. Hypoionic stress
      during dark anaerobic metabolism (autofermentation) was induced by resuspending
      filaments in low-sodium (bi)carbonate buffer (0.21 M), which resulted in
      accelerated autofermentation rates. For cells grown in 1.24 M NaCl, the
      fermentative yields of acetate, ethanol, and formate increase substantially to
      1.56, 0.75, and 1.54 mmol/(g [dry weight] of cells.day), respectively (36-, 121-,
      and 6-fold increases in rates relative to cells grown in 0.24 M NaCl). Catabolism
      of endogenous carbohydrate increased by approximately 2-fold upon hypoionic
      stress. For cultures grown at all salt concentrations, hydrogen was produced, but
      its yield did not correlate with increased catabolism of soluble carbohydrates.
      Instead, ethanol excretion becomes a preferred route for fermentative NADH
      reoxidation, together with intracellular accumulation of reduced products of
      acetyl coenzyme A (acetyl-CoA) formation when cells are hypoionically stressed.
      In the absence of hypoionic stress, hydrogen production is a major beneficial
      pathway for NAD(+) regeneration without wasting carbon intermediates such as
      ethanol derived from acetyl-CoA. This switch presumably improves the overall
      cellular economy by retaining carbon within the cell until aerobic conditions
      return and the acetyl unit can be used for biosynthesis or oxidized via
      respiration for a much greater energy return.

PMID- 20693451
TI  - Mutation of high-affinity methionine permease contributes to selenomethionyl
      protein production in Saccharomyces cerevisiae.
AB  - The production of selenomethionine (SeMet) derivatives of recombinant proteins
      allows phase determination by single-wavelength or multiwavelength anomalous
      dispersion phasing in X-ray crystallography, and this popular approach has
      permitted the crystal structures of numerous proteins to be determined. Although
      yeast is an ideal host for the production of large amounts of eukaryotic proteins
      that require posttranslational modification, the toxic effects of SeMet often
      interfere with the preparation of protein derivatives containing this compound.
      We previously isolated a mutant strain (SMR-94) of the methylotrophic yeast
      Pichia pastoris that is resistant to both SeMet and selenate and demonstrated its
      applicability for the production of proteins suitable for X-ray crystallographic
      analysis. However, the molecular basis for resistance to SeMet by the SMR-94
      strain remains unclear. Here, we report the characterization of SeMet-resistant
      mutants of Saccharomyces cerevisiae and the identification of a mutant allele of
      the MUP1 gene encoding high-affinity methionine permease, which confers SeMet
      resistance. Although the total methionine uptake by the mup1 mutant (the SRY5-7
      strain) decreased to 47% of the wild-type level, it was able to incorporate SeMet
      into the overexpressed epidermal growth factor peptide with 73% occupancy,
      indicating the importance of the moderate uptake of SeMet by amino acid permeases
      other than Mup1p for the alleviation of SeMet toxicity. In addition, under
      standard culture conditions, the mup1 mutant showed higher productivity of the
      SeMet derivative relative to other SeMet-resistant mutants. Based on these
      results, we conclude that the mup1 mutant would be useful for the preparation of
      selenomethionyl proteins for X-ray crystallography.

PMID- 20693452
TI  - Quantification of enteric viruses, pathogen indicators, and Salmonella bacteria
      in class B anaerobically digested biosolids by culture and molecular methods.
AB  - The most common class B biosolids in the United States are generated by
      mesophilic anaerobic digestion (MAD), and MAD biosolids have been used for land
      application. However, the pathogen levels in MAD biosolids are still unclear,
      especially with respect to enteric viruses. In this study, we determined the
      occurrence and the quantitative levels of enteric viruses and indicators in 12
      MAD biosolid samples and of Salmonella enterica in 6 MAD biosolid samples. Three
      dewatered biosolid samples were also included in this study for purposes of
      comparison. Human adenoviruses (HAdV) had the highest gene levels and were
      detected more frequently than other enteric viruses. The gene levels of
      noroviruses (NV) reported were comparable to those of enteroviruses (EV) and
      human polyomaviruses (HPyV). The occurrence percentages of HAdV, HAdV species F,
      EV, NV GI, NV GII, and HPyV in MAD samples were 83, 83, 42, 50, 75, and 58%,
      respectively. No hepatitis A virus was detected. Infectious HAdV was detected
      more frequently than infectious EV, and all infectious HAdV were detected when
      samples were propagated in A549 cells. Based on most-probable-number (MPN)
      analysis, A549 cells were more susceptible to biosolid-associated viruses than
      BGM cells. All indicator levels in MAD biosolids were approximately 10(4) MPN or
      PFU per gram (dry), and the dewatered biosolids had significantly higher
      indicator levels than the MAD biosolids. Only two MAD samples tested positive for
      Salmonella enterica, where the concentration was below 1.0 MPN/4 g. This study
      provides a broad comparison of the prevalence of different enteric viruses in MAD
      biosolids and reports the first detection of noroviruses in class B biosolids.
      The observed high quantitative and infectivity levels of adenoviruses in MAD
      biosolids indicate that adenovirus is a good indicator for the evaluation of
      sludge treatment efficiency.

PMID- 20693453
TI  - Design of thermostable beta-propeller phytases with activity over a broad range
      of pHs and their overproduction by Pichia pastoris.
AB  - Thermostable phytases, which are active over broad pH ranges, may be useful as
      feed additives, since they can resist the temperatures used in the feed-pelleting
      process. We designed new beta-propeller phytases, using a structure-guided
      consensus approach, from a set of amino acid sequences from Bacillus phytases and
      engineered Pichia pastoris strains to overproduce the enzymes. The recombinant
      phytases were N-glycosylated, had the correct amino-terminal sequence, showed
      activity over a pH range of 2.5 to 9, showed a high residual activity after 10
      min of heat treatment at 80 degrees C and pH 5.5 or 7.5, and were more
      thermostable at pH 7.5 than a recombinant form of phytase C from Bacillus
      subtilis (GenBank accession no. AAC31775). A structural analysis suggested that
      the higher thermostability may be due to a larger number of hydrogen bonds and to
      the presence of P257 in a surface loop. In addition, D336 likely plays an
      important role in the thermostability of the phytases at pH 7.5. The recombinant
      phytases showed higher thermostability at pH 5.5 than at pH 7.5. This difference
      was likely due to a different protein total charge at pH 5.5 from that at pH 7.5.
      The recombinant beta-propeller phytases described here may have potential as feed
      additives and in the pretreatment of vegetable flours used as ingredients in
      animal diets.

PMID- 20693455
TI  - Evaluating the growth potential of pathogenic bacteria in water.
AB  - The degree to which a water sample can potentially support the growth of human
      pathogens was evaluated. For this purpose, a pathogen growth potential (PGP)
      bioassay was developed based on the principles of conventional assimilable
      organic carbon (AOC) determination, but using pure cultures of selected
      pathogenic bacteria (Escherichia coli O157, Vibrio cholerae, or Pseudomonas
      aeruginosa) as the inoculum. We evaluated 19 water samples collected after
      different treatment steps from two drinking water production plants and a
      wastewater treatment plant and from ozone-treated river water. Each pathogen was
      batch grown to stationary phase in sterile water samples, and the concentration
      of cells produced was measured using flow cytometry. In addition, the fraction of
      AOC consumed by each pathogen was estimated. Pathogen growth did not correlate
      with dissolved organic carbon (DOC) concentration and correlated only weakly with
      the concentration of AOC. Furthermore, the three pathogens never grew to the same
      final concentration in any water sample, and the relative ratio of the cultures
      to each other was unique in each sample. These results suggest that the extent of
      pathogen growth is affected not only by the concentration but also by the
      composition of AOC. Through this bioassay, PGP can be included as a parameter in
      water treatment system design, control, and operation. Additionally, a multilevel
      concept that integrates the results from the bioassay into the bigger framework
      of pathogen growth in water is discussed. The proposed approach provides a first
      step for including pathogen growth into microbial risk assessment.

PMID- 20693454
TI  - Interrelations between the microbiotas in the litter and in the intestines of
      commercial broiler chickens.
AB  - The intestinal microbiota of broiler chickens and the microbiota in the litter
      have been well studied, but the interactions between these two microbiotas remain
      to be determined. Therefore, we examined their reciprocal effects by analyzing
      the intestinal microbiotas of broilers reared on fresh pine shavings versus
      reused litter, as well as the litter microbiota over a 6-week cycle. Composite
      ileal mucosal and cecal luminal samples from birds (n = 10) reared with both
      litter conditions (fresh versus reused) were collected at 7, 14, 21, and 42 days
      of age. Litter samples were also collected at days 7, 14, 21, and 42. The
      microbiotas were profiled and compared within sample types based on litter
      condition using PCR and denaturing gradient gel electrophoresis (PCR-DGGE). The
      microbiotas were further analyzed using 16S rRNA gene clone libraries constructed
      from microbiota DNA extracted from both chick intestinal and litter samples
      collected at day 7. Results showed significant reciprocal effects between the
      microbiotas present in the litter and those in the intestines of broilers. Fresh
      litter had more environmental bacteria, while reused litter contained more
      bacteria of intestinal origin. Lactobacillus spp. dominated the ileal mucosal
      microbiota of fresh-litter chicks, while a group of bacteria yet to be classified
      within Clostridiales dominated in the ileal mucosal microbiota in the reused
      litter chicks. The Litter condition (fresh versus reused) seemed to have a more
      profound impact on the ileal microbiota than on the cecal microbiota. The data
      suggest that the influence of fresh litter on ileal microbiota decreased as
      broilers grew, compared with temporal changes observed under reused-litter
      rearing conditions.

PMID- 20693457
TI  - StatBite: Physicians' role, as reported by patients, and trial enrollment rates.

PMID- 20693456
TI  - Distribution of Legionella species from environmental water sources of public
      facilities and genetic diversity of L. pneumophila serogroup 1 in South Korea.
AB  - A total of 560 Legionella species were isolated from environmental water sources
      from public facilities from June to September 2008 throughout South Korea. The
      distribution of Legionella isolates was investigated according to geographical
      region, facility type, and sample type. The genetic diversity of 104 isolates of
      Legionella pneumophila serogroup 1 (sg 1) was analyzed by sequence-based typing
      (SBT). L. pneumophila was distributed broadly throughout Korea, accounting for
      85.0% of the isolates, and L. pneumophila sg 1 predominated in all of the public
      facilities except for the springs. Legionella anisa and Legionella bozemanii
      predominated among non-L. pneumophila species (48.1% and 21.0%, respectively).
      The second most dominant strain differed depending on the facility type: L. anisa
      was the second most dominant strain in the buildings (10.8%), L. pneumophila sg 5
      in public baths (21.6%), L. pneumophila sg 6 in factories (12.0%), and L.
      pneumophila sg 7 in hospitals (13.1%). In the SBT analysis, 104 L. pneumophila sg
      1 isolates were differentiated into 26 sequence types (STs) and categorized into
      3 clonal groups (CGs) and 10 singleton STs via the eBURST V3 program. ST1, a
      potential founder of major CG1, was commonly distributed (48.1%). The dominant ST
      in hot water was ST-K1 (7, 12, 17, 3, 35, 11, 11), which was designated in this
      study (36.1%). The second most dominant strain differed depending on the type of
      facility from which the samples were obtained. The unique allelic profile of ST
      K1, obtained from hot water, was not found in the European Working Group for
      Legionella Infections (EWGLI) SBT database.

PMID- 20693458
TI  - Shaking up cancer clinical trials: an interview with John Mendelsohn, M.D., by
      Joanne Nicholas.

PMID- 20693459
TI  - Adaptive clinical trial design: has its time come?

PMID- 20693460
TI  - Large trials, small gains: is change on the way?

PMID- 20693461
TI  - Open-source science makes headway.

PMID- 20693462
TI  - The complexity of complex PTSD.

PMID- 20693463
TI  - An opioid deficit in borderline personality disorder: self-cutting, substance
      abuse, and social dysfunction.

PMID- 20693464
TI  - Abrupt withdrawal of antidepressant treatment.

PMID- 20693465
TI  - S-adenosyl methionine (SAMe) augmentation in major depressive disorder.

PMID- 20693466
TI  - Bipolar disorder and pregnancy: maintaining psychiatric stability in the real
      world of obstetric and psychiatric complications.

PMID- 20693467
TI  - Samuel Tuke's description of the Retreat.

PMID- 20693469
TI  - Analysis of antipsychotic dose reduction.

PMID- 20693471
TI  - The value of data on suicidality by treatment arm.

PMID- 20693473
TI  - Placebo group needed for interpretation of combination trial.

PMID- 20693475
TI  - The difficulty of making a sole diagnosis of anti-social personality disorder.

PMID- 20693476
TI  - Elevated prevalence of generalized anxiety disorder in adults with 22q11.2
      deletion syndrome.

PMID- 20693478
TI  - CRX ChIP-seq reveals the cis-regulatory architecture of mouse photoreceptors.
AB  - Approximately 98% of mammalian DNA is noncoding, yet we understand relatively
      little about the function of this enigmatic portion of the genome. The cis
      regulatory elements that control gene expression reside in noncoding regions and
      can be identified by mapping the binding sites of tissue-specific transcription
      factors. Cone-rod homeobox (CRX) is a key transcription factor in photoreceptor
      differentiation and survival, but its in vivo targets are largely unknown. Here,
      we used chromatin immunoprecipitation with massively parallel sequencing (ChIP
      seq) on CRX to identify thousands of cis-regulatory regions around photoreceptor
      genes in adult mouse retina. CRX directly regulates downstream photoreceptor
      transcription factors and their target genes via a network of spatially
      distributed regulatory elements around each locus. CRX-bound regions act in a
      synergistic fashion to activate transcription and contain multiple CRX binding
      sites which interact in a spacing- and orientation-dependent manner to fine-tune
      transcript levels. CRX ChIP-seq was also performed on Nrl(-/-) retinas, which
      represent an enriched source of cone photoreceptors. Comparison with the wild
      type ChIP-seq data set identified numerous rod- and cone-specific CRX-bound
      regions as well as many shared elements. Thus, CRX combinatorially orchestrates
      the transcriptional networks of both rods and cones by coordinating the
      expression of photoreceptor genes including most retinal disease genes. In
      addition, this study pinpoints thousands of noncoding regions of relevance to
      both Mendelian and complex retinal disease.

PMID- 20693479
TI  - Optimization of de novo transcriptome assembly from next-generation sequencing
      data.
AB  - Transcriptome analysis has important applications in many biological fields.
      However, assembling a transcriptome without a known reference remains a
      challenging task requiring algorithmic improvements. We present two methods for
      substantially improving transcriptome de novo assembly. The first method relies
      on the observation that the use of a single k-mer length by current de novo
      assemblers is suboptimal to assemble transcriptomes where the sequence coverage
      of transcripts is highly heterogeneous. We present the Multiple-k method in which
      various k-mer lengths are used for de novo transcriptome assembly. We demonstrate
      its good performance by assembling de novo a published next-generation
      transcriptome sequence data set of Aedes aegypti, using the existing genome to
      check the accuracy of our method. The second method relies on the use of a
      reference proteome to improve the de novo assembly. We developed the Scaffolding
      using Translation Mapping (STM) method that uses mapping against the closest
      available reference proteome for scaffolding contigs that map onto the same
      protein. In a controlled experiment using simulated data, we show that the STM
      method considerably improves the assembly, with few errors. We applied these two
      methods to assemble the transcriptome of the non-model catfish Loricaria gr.
      cataphracta. Using the Multiple-k and STM methods, the assembly increases in
      contiguity and in gene identification, showing that our methods clearly improve
      quality and can be widely used. The new methods were used to assemble
      successfully the transcripts of the core set of genes regulating tooth
      development in vertebrates, while classic de novo assembly failed.

PMID- 20693480
TI  - Massive turnover of functional sequence in human and other mammalian genomes.
AB  - Despite the availability of dozens of animal genome sequences, two key questions
      remain unanswered: First, what fraction of any species' genome confers biological
      function, and second, are apparent differences in organismal complexity reflected
      in an objective measure of genomic complexity? Here, we address both questions by
      applying, across the mammalian phylogeny, an evolutionary model that estimates
      the amount of functional DNA that is shared between two species' genomes. Our
      main findings are, first, that as the divergence between mammalian species
      increases, the predicted amount of pairwise shared functional sequence drops off
      dramatically. We show by simulations that this is not an artifact of the method,
      but rather indicates that functional (and mostly noncoding) sequence is turning
      over at a very high rate. We estimate that between 200 and 300 Mb (~6.5%-10%) of
      the human genome is under functional constraint, which includes five to eight
      times as many constrained noncoding bases than bases that code for protein. In
      contrast, in D. melanogaster we estimate only 56-66 Mb to be constrained,
      implying a ratio of noncoding to coding constrained bases of about 2. This
      suggests that, rather than genome size or protein-coding gene complement, it is
      the number of functional bases that might best mirror our naive preconceptions of
      organismal complexity.

PMID- 20693481
TI  - Signatures of positive selection apparent in a small sample of human exomes.
AB  - Exome sequences, which comprise all protein-coding regions, are promising data
      sets for studies of natural selection because they offer unbiased genome-wide
      estimates of polymorphism while focusing on the portions of the genome that are
      most likely to be functionally important. We examine genomic patterns of
      polymorphism within 10 diploid autosomal exomes of European and African descent.
      Using coalescent simulations, we show how polymorphism, site frequency spectra,
      and intercontinental divergence in these samples would be influenced by different
      modes of positive selection. We examine putatively selected loci from four
      previous genome-wide scans of SNP genotypes and demonstrate that these regions
      indeed show unusual population genetic patterns in the exome data. Using a series
      of conservative criteria based on exome polymorphism, we are able to fine-scale
      map signatures of selection, in many cases pinpointing a single candidate SNP. We
      also identify and evaluate novel candidate selection genes that show unusual
      patterns of polymorphism. We sequence a portion of one novel candidate locus,
      IVL, in 74 individuals from multiple continents and examine global genetic
      diversity. Thus, we confirm, narrow, and supplement existing catalogs of putative
      targets of selection, and show that exome data sets, which are likely to soon
      become common, will be powerful tools for identifying adaptive genetic variation.

PMID- 20693482
TI  - How the public responded to the Schiavo controversy: evidence from letters to
      editors.
AB  - The history and genesis of major public clinical ethics controversies is
      intimately related to the publication of opinions and responses in media
      coverage. To provide a sample of public response in the media, this paper reports
      the results of a content analysis of letters to editors published in the four
      most prolific American newspapers for the Schiavo controversy. Opinions expressed
      in the letters sampled strongly supported the use of living wills and strongly
      condemned public attention to the case as well as political interventions.
      Letters tended to be against withdrawal of life support, proxy consent and
      associated procedures as well as against court decisions and legal procedures. In
      comparison with reports written by journalists, letters to editors contained
      fewer controversial claims about Schiavo''s neurological condition and
      behavioural repertoire but similar loaded language to describe withdrawal of life
      support. Distinct public discourses can be encountered in different stakeholders
      suggesting complex and extensive pluralism even within the media.

PMID- 20693483
TI  - The moral primacy of the human being.
AB  - Can the view that medical science is more important than the individual properly
      persuade recruitment to trials? This paper considers the nature and interests of
      the person and their relationships to the concepts of science and society; and
      analyses a conception of value used to balance the interests of science and
      research subjects. The implications of arguments opposing the primacy of the
      individual are set out to indicate their implausibility; while the primacy
      principle is described to show its necessity in any moral society. Finally, the
      importance of fully informed consent to participate is explained with the
      requirement that the individual human life provide the criteria of moral value
      for human life.

PMID- 20693484
TI  - Comparison of two intravitreal ranibizumab treatment schedules for neovascular
      age-related macular degeneration.
AB  - INTRODUCTION: Ranibizumab (Lucentis), a humanised antibody fragment that inhibits
      vascular endothelial growth factor (VEGF)-A, is widely used for the treatment of
      neovascular age-related macular degeneration (NV-AMD). The objective of this
      study was to compare the outcomes of two different treatment protocols: loading
      dose (LD) and pro re nata (PRN (as needed)) dosing schedule from baseline.
      METHODS: This retrospective chart review was conducted at King's College
      Hospital, London, UK. Consecutive patients were identified using the 'Ranibizumab
      in NV-AMD' database. These patients had treatment-naive choroidal
      neovascularisation (CNV) secondary to AMD, received ranibizumab therapy and had
      completed 12 months of follow-up. Baseline examination included visual acuity
      (Early Treatment Diabetic Retinopathy Study (ETDRS) letters), slit-lamp
      biomicroscopy, fluorescein angiography, and qualitative and quantitative
      assessment of central macular characteristics on optical coherent tomography
      (OCT). Intravitreal ranibizumab (0.5mg/0.05ml) was given to all patients at
      baseline. Patients on LD regimen received two further consecutive monthly
      intravitreal ranibizumab injections independent of clinical findings. Further
      injections were determined by the same re-treatment criteria as patients on PRN
      schedule from baseline. The main outcome variables in the two treatment groups
      were visual acuity and central macular thickness at different time points.
      RESULTS: The LD group contained 47 patients and the PRN group contained 31
      patients. There were no significant differences between groups in the mean
      changes in visual acuity or central macular thickness. Visual acuity was similar
      in both groups at 6&emsp14;months. However, twice as many patients improved
      visual acuity by 15 or more letters in the LD group (29.8% in the LD group
      compared with 12.9% in the PRN group (p=0.01)). CONCLUSION: This study showed
      that standard protocols used for OCT-guided retreatment achieved smaller mean
      gains in vision than those obtained with monthly ranibizumab administration.
      Further, loading doses of ranibizumab resulted in more visual gains than the PRN
      protocol.

PMID- 20693485
TI  - Hypertensive retinopathy in a child.

PMID- 20693486
TI  - Prediction error and myopic shift after intraocular lens implantation in
      paediatric cataract patients.
AB  - AIM: To determine the amount of myopic shift in children after cataract surgery
      with intraocular lens (IOL) implantation and to evaluate success in achieving the
      target refraction. METHODS: The children were assigned into three groups
      depending on age at time of surgery: Group A, 0-1 years old; Group B, 1-7 years
      old; Group C, 7-18 years old. Multiple regression analysis was used to create a
      formula for expected myopic shift and to find out which variables were associated
      with a higher absolute prediction error. RESULTS: Children less than 12 months of
      age experienced higher myopic shifts and a larger mean rate of refractive change
      per year compared with older children. We found higher myopic shifts in younger
      children at time of surgery and children with unilateral cataract. Absolute
      prediction error was significantly higher in Group A compared with Groups B and C
      (p=0.022 and p=0.037, respectively). Multiple regression analysis showed that
      corneal radius was the only variable significantly associated with absolute
      prediction error. CONCLUSION: Our data demonstrate the complexity in predicting
      the postoperative refraction in children under 1 year old and show that age at
      surgery and laterality are factors to consider when deciding which IOL power to
      implant in children.

PMID- 20693487
TI  - Influence of previous vitrectomy on incidence of macular oedema after cataract
      surgery in diabetic eyes.
AB  - PURPOSE: To evaluate the effect of previous vitrectomy on the incidence of
      macular oedema (MO) after cataract surgery in diabetic eyes. METHODS: Ninety
      phakic eyes of 70 patients with diabetes undergoing non-emergent vitrectomy
      surgery were reviewed for rates of postvitrectomy MO, cataract formation and
      postcataract surgery MO. Preoperative and final best-corrected visual acuity were
      recorded. Baseline risk characteristics were analysed. RESULTS: Postvitrectomy MO
      increases initially but then levels off at 28% by 4 years. Cumulative proportion
      of eyes requiring cataract surgery after vitrectomy climbs steadily, reaching 40%
      at 4 years and 60% at 8 years. Of those eyes which underwent vitrectomy and then
      subsequent cataract surgery, the incidence of postvitrectomy MO was 6% at 6
      months, and that of postcataract surgery MO was 30% at 6 months (p<0.02).
      Previous clinically significant macular oedema (CSMO) predicted development of
      postcataract surgery MO (p<0.04). CONCLUSIONS: Previous vitrectomy does not
      appear to lessen rates of postcataract surgery MO. Cataract formation is common
      after vitrectomy in diabetic eyes, and risk of postcataract surgery MO is
      substantial and more likely in eyes with prior CSMO. Cataract formation and risk
      of postcataract surgery MO should be considered when assessing the long-term
      benefits of vitrectomy surgery in patients with diabetes.

PMID- 20693488
TI  - New approach in training in East Africa: vitreo-retinal surgery from 2000 to 2007
      in Kenya.

PMID- 20693489
TI  - Effects of intervention with the SAFE strategy on trachoma across Ethiopia.
AB  - BACKGROUND/AIMS: The impact of the SAFE strategy (surgery, antibiotics, face
      washing, environmental hygiene), recommended to eliminate blinding trachoma, is
      not well explored. We determined the operational effectiveness of the whole SAFE
      intervention package. METHODS: Analytical cross-sectional trachoma surveys were
      conducted in four program areas across Ethiopia before and after 3 years of
      intervention with the SAFE strategy. A total of 8358 children 1-9 years, 4684
      people above 14 and 3572 households were assessed in the follow-up evaluations
      using methodologies recommended by the WHO. Effects were measured by comparing
      follow-up proportions with baseline estimates of four key indicators. RESULTS:
      Coverage was 36% for trichiasis surgery, 59% for antibiotic and 57% for health
      promotion services. Prevalence of trachoma trichiasis (TT) decreased from 4.6%
      (95% CI: 3.6% to 5.8%) down to 2.9% (CI: 2.1% to 3.9%). Prevalence of trachoma
      inflammation-follicular (TF) dropped from 36.7% (33.9% to 39.6%) to 18.4% (CI:
      15.4% to 21.8%). The proportion of unclean faces and households not using
      latrines fell from 72.8% (68.9% to 76.4%) and 74.5% (69.9% to 78.7%) down to
      47.0% (CI: 43% to 51%) and 51.7% (47.2% to 56.2%), respectively. All the
      reductions related with antibiotic (TF), face washing (clean face) and
      environmental (latrine) components were statistically significant except for
      Surgery (TT). CONCLUSIONS: Considerable decline in the magnitude of trachoma and
      its risk factors was observed in areas where the SAFE strategy was implemented.
      The coverage of services should be maintained or improved in order to eliminate
      blinding trachoma by the year 2020.

PMID- 20693490
TI  - Socioeconomic status is not associated with type 2 diabetes incidence in an
      elderly population in Germany: KORA S4/F4 cohort study.
AB  - BACKGROUND: An association between socioeconomic status (SES) and the incidence
      of type 2 diabetes mellitus (T2DM) has been found for younger and middle-aged
      individuals, but studies of this relationship in elderly populations are rare.
      METHODS: In a population-based cohort in southern Germany (KORA S4/F4: 1223
      subjects aged 55-74 years at baseline, 887 subjects (73%) in the follow-up 7
      years later) the identification of incident T2DM was based on oral glucose
      tolerance tests or on validated physician diagnoses. Regression models were
      fitted to predict incident T2DM and (pre)diabetes, respectively, with SES as the
      main independent variable. (Pre)diabetes here means incident T2DM or incident pre
      diabetes. RESULTS: With five different SES measures (global Helmert index,
      income, educational level, occupational status, subjective social status), the
      diabetes risk of low SES groups was not significantly different from the risk of
      higher SES groups (ie, cumulative incidence 10% (low income), 9% (medium income),
      13% (high income)). In subjects with normoglycaemia at baseline, (pre)diabetes
      incidence was more pronounced in lower SES groups, but almost all these
      associations were not significant. With measures of subjective SES stronger
      associations were found than with measures of objective SES. CONCLUSION: There
      was no statistically significant association between objective SES and diabetes
      incidence in this elderly population. This might be due to a larger socioeconomic
      homogeneity of elderly populations and to a strong driving force for diabetes,
      which outweighed the influence of SES, and which was indicated by an adverse
      baseline metabolic profile in participants developing diabetes in the follow-up.

PMID- 20693491
TI  - Moderate coffee consumption reduces the risk of hepatocellular carcinoma in
      hepatitis B chronic carriers: a case-control study.
AB  - BACKGROUND: Recent epidemiological studies have reported a dose-dependent
      protective effect of coffee on hepatocellular carcinoma (HCC) with risk reduction
      ranging from 30% to 80% in daily coffee drinkers compared with non-drinkers. This
      study examined whether coffee has a similar protective effect when consumed in
      moderate quantities in chronic hepatitis B virus (HBV) carriers, a group at high
      risk of developing liver cancer. METHODS: A case-control design was employed. 234
      HBV chronic carriers (109 cases and 125 controls) were recruited from the Prince
      of Wales Hospital in Hong Kong from December 2007 to May 2008. Data collection
      included review of medical records and face-to-face interview. Univariate and
      multivariate logistic regressions adjusting for age, gender, cigarette smoking,
      alcohol use, tea consumption and physical activity were conducted with dose
      response analysis. RESULTS: Moderate coffee consumption significantly reduced the
      risk of HCC by almost half (OR 0.54, 95% CI 0.30 to 0.97) with a significant dose
      response effect (chi2=5.41, df=1, p=0.02), reducing the risk for moderate
      drinkers by 59% (OR 0.41, 95% CI 0.19 to 0.89). CONCLUSION: The findings provided
      evidence to support the protective effect of coffee consumption in moderate
      quantities in HBV chronic carriers.

PMID- 20693492
TI  - Proximal predictors of change in quality of life at older ages.
AB  - OBJECTIVE: To investigate whether changes in health, social and economic
      circumstances predict change in quality of life (QoL) at older ages. DESIGN:
      Secondary analysis, using multiple regression analyses, of waves 1 and 3 of the
      English Longitudinal Study of Ageing. SETTING: England, 2002-6. PARTICIPANTS: A
      nationally representative sample of non-institutionalised adults aged over 50
      years living in England with non-missing data for the variables of interest
      (N=4848). MAIN OUTCOME MEASURE: QoL in 2006, with reference to QoL in 2002, both
      measured using the CASP-19 score. RESULTS: Mean QoL decreased over the
      4&emsp14;years, with becoming depressed (beta -0.12) and developing difficulties
      with activities of daily living (beta -0.08) contributing to this decrease.
      Improvements in family relationships (beta 0.10), the neighbourhood (beta 0.08)
      and perceived financial position (beta 0.07) each counteracted the decline in
      QoL. Initial QoL strongly predicted QoL at follow-up (beta 0.46). Regression
      models explained 59% of variation in QoL, and there were small differences
      between age and gender groups. CONCLUSIONS: The maintenance of good QoL in older
      aged people is enabled by the avoidance of depression, maintenance of physical
      function, good neighbourhood standards, family relationships and financial
      circumstances.

PMID- 20693493
TI  - Deaths in collective dwellings and inequalities in small-area mortality: an
      ecological study in the Madrid region (Spain).
AB  - BACKGROUND: Increasing numbers of elderly persons reside and die in institutions,
      yet there are few studies that analyse the effect of this on mortality in small
      areas and its ensuing effect on the association between material deprivation and
      mortality. METHODS: A cross-sectional, ecological study in the region of Madrid
      covering 3906 census tracts (median 1000 inhabitants), using mortality data for
      1996-2003 and socioeconomic deprivation from the 2001 census. Standardised
      mortality ratios (SMR) were calculated for each census tract. Using the Besag
      York-Mollie model, RR of dying and their 95% CI according to the deprivation
      index considered (with the fourth quartile, Q, being the most unfavourable
      situation) were calculated for deaths among: the total population and the
      population excluding residents who died in institutions. RESULTS: 6% of the
      deceased had been residing in institutions, which affected 16.5% of census
      sections (644) and accounted for 17% of the variability in SMR among men and 10%
      among women, p<0.001. Mortality increased with socioeconomic deprivation, whereas
      the RR for the total population in Q4 with respect to Q1 was 1.46 among men (95%
      CI 1.41 to 1.50) and 1.12 among women (95% CI 1.08 to 1.17), these figures rose
      to 1.48 (95% CI 1.43 to 1.53) and 1.14 (95% CI 1.10 to 1.18), respectively, for
      the population excluding residents who died in institutions. CONCLUSIONS: Deaths
      of residents in institutions affect the variation in small-area mortality, and
      confound the relationship between mortality and socioeconomic deprivation. This
      variable should be recorded in mortality statistics so that its effect can be
      controlled for in subsequent analyses.

PMID- 20693494
TI  - Differences in 5-year survival after a 'homeless' or 'housed' drugs-related
      hospital admission: a study of 15--30-year olds in Scotland.
AB  - BACKGROUND: Young drug misusers and the homeless both have a greater risk of
      death than their peers. This study sought to estimate the additional impact of
      homelessness on the risk of death for young drugs misusers. METHODS: From all
      admissions to NHS hospitals in Scotland between 1986 and 2001, those that were:
      drug misuse related, for people born between 1970 and 1986 and aged over 15 years
      (n=13 303), were selected. All subsequent admissions and registrations of death
      were linked to this dataset. Each admission was coded as homeless if the health
      board of residence was coded as 'no fixed abode'. 5-year survival after an
      admission was modelled using (1) life table and (2) proportional hazard models
      and then (3) differences in causes of deaths were explored. RESULTS: Immediately
      after a drugs-related hospital admission there was no difference in survival
      between the homeless and those with a 'fixed address'. However, over a 3-year
      period the risk for those who were homeless was 3.5 times greater (CI 95% 1.2 to
      12.8). This elevated risk seemed to be particularly focused on the second year
      after an admission. The causes of death were similar for the two groups.
      CONCLUSION: Although a homeless hospital admission is associated with a greater
      risk of death for young drug users, it is also a point in time when a young
      person is in contact with public services. An attempt to link their discharge
      with housing services would seem a potentially productive policy.

PMID- 20693495
TI  - Factors associated with antihypertensive drug compliance in 83,884 Chinese
      patients: a cohort study.
AB  - BACKGROUND: Few studies address the profiles of antihypertensive compliance among
      ethnic Chinese. The levels of and factors associated with antihypertensive drug
      compliance among Chinese patients were evaluated in this study. METHODS: All
      Chinese hypertensive patients who paid at least two consecutive visits in any
      government primary care clinics for antihypertensive drug refill in a large
      territory of Hong Kong from January 2004 to June 2007 were included. Medication
      possession ratio (MPR), defined as the ratio of total days of medication supplied
      (not including the last prescription) to total days in a period of time, was used
      a measure of drug compliance. RESULTS: From 83,884 eligible patients, 71,685
      (85.5%) had good compliance to antihypertensive drugs (MPR>or=80%). Binary
      logistic regression analysis was conducted, with good compliance as the outcome
      variable while controlling for potential confounders. Advanced age (adjusted ORs
      (aOR) 1.36-1.55, p<0.001), female gender (aOR for male patients 0.84, 95% CI 0.80
      to 0.87, p<0.001), payment of fees (aOR 1.14, 95% CI 1.09 to 1.19, p<0.001),
      attendance in family medicine specialist clinic (aOR 1.52, 95% CI 1.40 to 1.66,
      p<0.001), follow-up visits (aOR 3.21, 95% CI 3.06 to 3.36, p<0.001) and use of
      drugs acting on the renin-angiotensin system (aOR 1.18, 95% CI 1.07 to 1.30,
      p=0.001) were positively associated with good compliance to drugs. Use of beta
      blockers was negatively associated with drug compliance (aOR 0.78, 95% CI 0.73 to
      0.84, p<0.001). CONCLUSIONS: Physicians should practice caution when prescribing
      antihypertensive drugs to patients with these factors where closer monitoring of
      their compliance patterns is warranted.

PMID- 20693496
TI  - Heterogeneous trend in smoking prevalence by sex and age group following the
      implementation of a national smoke-free law.
AB  - OBJECTIVE: Given the limited evidence available about the effects of clean indoor
      air laws on smoking behaviour in the general population, the impact of national
      smoke-free workplace, bar and restaurant legislation, implemented on 1 January
      2006, on smoking prevalence in Spain was assessed in this study. METHODS:
      Population-based trend analysis using estimates for 27 periods from the beginning
      of 2000 to the end of 2008-three periods per year. To calculate the period per
      cent change in smoking prevalence, the permutation test for joinpoint regression
      to detect significant changes was used. RESULTS: In men and women aged 15-24
      years, the prevalence of smoking declined between the first period in 2000 and
      the third period in 2008, whereas in women aged 45-64 years, it increased by 1.7%
      per period. A declining trend was detected up to the first period in 2006 in men
      and women aged 25-44 years and in men aged 45-64 years, but between the beginning
      of 2006 and the end of 2008 the prevalence of smoking increased by 1.2%, 0.7% and
      2.0% per period in men aged 25-44 years, in women aged 25-44 years and in men
      aged 45-64 years, respectively. CONCLUSIONS: 3 years after a national smoke-free
      law was implemented, the trend in smoking prevalence in some population groups
      was unchanged; however, in others, the declining trend of previous years was
      reversed. The similarity of these findings to those observed in other countries
      suggests that clean indoor air laws, although effective in reducing exposure to
      second-hand smoke, may not achieve the secondary objective of reducing the
      prevalence of smoking in the population.

PMID- 20693497
TI  - Welfare regimes, labour policies and unhealthy psychosocial working conditions: a
      comparative study with 9917 older employees from 12 European countries.
AB  - BACKGROUND: Recent analyses explored associations of welfare state regimes with
      population health, with particular interest in differences between social
      protection-oriented versus more liberal regimes. Little is known about such
      associations with work-related health. The aims of this contribution are (1) to
      study variations of quality of work according to type of welfare regime and (2)
      to analyse differences in the size of effects of quality of work on workers'
      health according to type of welfare regime. METHODS: The authors use cross
      sectional and longitudinal data from two studies ('Survey of Health, Ageing and
      Retirement in Europe' and the 'English Longitudinal Study on Ageing') with 9917
      employed men and women (aged 50 to 64) in 12 European countries. Psychosocial
      quality of work is measured by low control and effort-reward imbalance at work.
      Depressive symptoms are introduced as a health indicator. Linear multilevel
      models and logistic regression analyses are performed to test the hypotheses. In
      addition to the welfare regime typology, the authors introduce labour policy and
      economy-related macro indicators. RESULTS: Between-country variations in quality
      of work are largely explained by macro indicators and welfare regimes, with
      poorer quality of work in countries with less emphasis on older workers'
      protection. Moreover, in the Liberal and Southern welfare regime, effects of
      quality of work on depressive symptoms are relatively strongest (adjusted ORs
      varying from 1.45 to 2.64). CONCLUSION: Active labour policies and reliable
      social protection measures (eg, Scandinavian welfare regime) exert beneficial
      effects on the health and well-being of older workers. More emphasis on improving
      quality of work among this group is warranted.

PMID- 20693498
TI  - Potential risk factors associated with subtypes of uterine leiomyomata.
AB  - OBJECTIVE: To compare potential risk factors for uterine leiomyomata (UL)
      subtypes among premenopausal African American and Caucasian women. METHODS: This
      cross-sectional study included 986 premenopausal women, aged 35 to 49 years old,
      from the National Institute of Environmental Health Sciences (NIEHS) Uterine
      Fibroid Study (UFS). Uterine leiomyomata were subtyped as submucosal,
      intramural/subserosal, and diffuse, based on ultrasound examinations. RESULTS:
      For both ethnic groups, age, age at menarche, body mass index, and current
      physical activity had similar associations across the 3 UL subtypes. Inverse
      associations with pregnancies after age 24 appeared to be stronger for the
      submucosal subtype. Current smoking was associated only with diffuse UL (adjusted
      odds ratio [aOR] = 1.97, 95% CI: 1.11, 3.51 in African Americans, aOR = 3.00, 95%
      CI: 1.07, 8.38 in Caucasians). CONCLUSIONS: Although the 2 focal UL subtypes had
      similar risk factor profiles, the diffuse UL subtype appeared to have a
      distinctive risk profile with regard to current smoking. Further study of the
      diffuse heterogeneity seen with uterine ultrasound is needed.

PMID- 20693501
TI  - International disease monitoring, April to June.

PMID- 20693500
TI  - Multiple anticancer activities of EF24, a novel curcumin analog, on human ovarian
      carcinoma cells.
AB  - Curcumin, a component of turmeric, has been reported to exhibit potential
      antitumor activities. This study assessed the effects of a novel synthetic
      curcumin analog, EF24, on proliferation, apoptosis, and vascular endothelial
      growth factor (VEGF) regulation in platinum-sensitive (IGROV1) and platinum
      resistant (SK-OV-3) human ovarian cancer cells. EF24 time- and dose-dependently
      suppressed the growth of both cell lines and synergized with cisplatin to induce
      apoptosis. Although treatment with EF24 had no significant effect on VEGF
      messenger RNA (mRNA) expression,VEGF protein secretion into conditioned media was
      dose-dependently reduced with EF24 demonstrating ~8-fold greater potency than
      curcumin (P < .05). EF24 significantly inhibited hydrogen peroxide (H(2)O(2))
      induced VEGF expression, as did the phenolic antioxidant tert-butylhydroquinone
      (t-BHQ). EF24 upregulated cellular antioxidant responses as observed by the
      suppression of reactive oxygen species (ROS) generation and activation of
      antioxidant response element (ARE)-dependent gene transcription. Given its high
      potency, EF24 is an excellent lead candidate for further development as an
      adjuvant therapeutic agent in preclinical models of ovarian cancer.

PMID- 20693499
TI  - Absence of mitochondrial progesterone receptor polymorphisms in women with
      spontaneous preterm birth.
AB  - OBJECTIVE: The truncated mitochondrial progesterone receptor (PR-M) is homologous
      to nuclear PRs with the exception of an amino terminus hydrophobic membrane
      localization sequence, which localizes PR-M to mitochondria. Given the
      matrilineal inheritance of both spontaneous preterm birth (SPTB) and the
      mitochondrial genome, we hypothesized that (a) PR-M is polymorphic and (b) PR-M
      localization sequence polymorphisms could result in variable progesterone
      mitochondrial effects and variable responsiveness to progesterone prophylaxis.
      METHODS: Secondary analysis of DNA from women enrolled in a multicenter,
      prospective, study of 17 alpha-hydroxyprogesterone caproate (17OHPC) versus
      placebo for the prevention of recurrent SPTB. DNA was extracted from stored
      saliva. RESULTS: The PR-M localization sequence was sequenced on 344 patients.
      Sequences were compared with the previously published 48 base-pair sequence, and
      all were identical. CONCLUSIONS: We did not detect genetic variation in the
      mitochondrial localization sequence of the truncated PR-M in a group of women at
      high risk for SPTB.

PMID- 20693502
TI  - Epidemiology of canine parvovirus and coronavirus in dogs presented with severe
      diarrhoea to PDSA PetAid hospitals.
AB  - Canine parvovirus (CPV) and canine enteric coronavirus (CECoV) are often cited as
      causes of diarrhoea in dogs. This study aimed to determine the prevalence of CPV
      and CECoV in dogs presenting with severe diarrhoea to PDSA PetAid hospitals
      throughout the UK. A total of 355 samples were collected from the PDSA between
      2006 and 2008. All samples were tested for CPV using a long range PCR and for
      CECoV using RT-PCR. The prevalence of CPV was 58 per cent (95 per cent confidence
      interval [CI] 52 to 63 per cent), with some evidence for regional variation. The
      prevalence of CECoV was 7.9 per cent (95 per cent CI 5.1 to 10.7 per cent).
      Analysis showed that animals with no history of vaccination were more likely to
      be CPV positive, with greatest effect in younger animals. CPV-positive animals
      were more likely to present with depression/lethargy than CPV-negative cases. The
      volume of diarrhoea and the presence of haemorrhage did not appear to be
      associated with the likelihood of detecting CPV. This study shows that CPV is a
      common finding in dogs presenting to PDSA hospitals with severe diarrhoea, and
      that CECoV is a less common but still potentially important pathogen. It also
      confirms that young and unvaccinated animals appear to be more at risk of
      presenting with CPV.

PMID- 20693503
TI  - Risk factors for seropositivity to bovine coronavirus and bovine respiratory
      syncytial virus in dairy herds.
AB  - A cross-sectional study was conducted to evaluate the association between herd
      level characteristics, management routines and farm-level antibody status of
      bovine coronavirus (BCV) and bovine respiratory syncytial virus (BRSV) in 257
      Swedish dairy herds. The possible spatial clustering of positive herds compared
      with negative herds was also investigated. For each herd, a pooled milk sample
      from five primiparous cows was analysed for the presence of antibodies to BCV and
      BRSV. Herd-level information was obtained by a questionnaire. Logistic regression
      was used to evaluate the association between predictors and antibody status to
      BCV and BRSV. Large herd size, being located in southern Sweden, and not
      providing boots for visitors were found to be associated with being antibody
      positive to BCV and BRSV. A short distance to the nearest cattle herd was an
      additional risk factor for BCV. One of the studied areas was suitable for spatial
      analysis. Positive herds were not spatially autocorrelated when compared with
      negative herds as estimated by the K-function regarding both BCV and BRSV. This
      indicates that local factors such as daily visiting milk trucks and wild animals
      were unlikely to be important sources of infection in this area. Moran's I
      statistics and semi-variogram showed no evidence of spatial autocorrelation in
      the residuals, indicating that remaining unidentified factors are not spatially
      dependent in the areas under study.

PMID- 20693504
TI  - Ultrasonographic evaluation of adrenal glands in dogs with primary
      hypoadrenocorticism or mimicking diseases.
AB  - The adrenal glands of 30 dogs with primary adrenal insufficiency
      (hypoadrenocorticism) were measured ultrasonographically and compared with those
      of 14 healthy dogs and those of 10 dogs with diseases mimicking
      hypoadrenocorticism. Thickness and length of the adrenals were measured on
      abdominal ultrasonography and the results for each group were compared. Dogs with
      primary hypoadrenocorticism had significantly thinner adrenals compared with the
      other two groups, and their left adrenal glands were also significantly shorter
      than those of healthy dogs. Adrenal ultrasonography may be of diagnostic value in
      dogs with clinical signs suggestive of primary hypoadrenocorticism, as a left
      adrenal gland measuring less than 3.2 mm in thickness is strongly suggestive of
      the disease.

PMID- 20693505
TI  - Cross-sectional study of Streptococcus species in quarter milk samples of dairy
      cows in the canton of Bern, Switzerland.
AB  - A total of 2538 quarter milk samples from 638 lactating dairy cows from 47 farms
      in the canton of Bern, Switzerland, were investigated for streptococci. A novel,
      simple and inexpensive laboratory method was used for the differentiation of
      Streptococcus species, and a risk factor analysis was carried out. The prevalence
      in the quarter milk samples was 0.2 per cent for Streptococcus agalactiae, 1.3
      per cent for Streptococcus uberis, 1.3 per cent for Streptococcus dysgalactiae,
      0.1 per cent for Enterococcus species and 2.9 per cent for minor Streptococcus
      species (designated Streptococcus-Lactococcus-Enterococcus [SLE] group). Based on
      the somatic cell count (SCC), S uberis and S dysgalactiae were classified as
      'major' pathogens and the bacteria in the SLE group as 'minor' pathogens. For S
      uberis, S dysgalactiae and bacteria in the SLE group, the most significant risk
      factor was an intramammary infection (IMI) of a neighbouring quarter by the same
      pathogen. Other significant risk factors for S uberis infection were a positive
      California Mastitis Test (CMT) result and a SCC of more than 100,000 cells/ml.
      Significant risk factors for IMI with S dysgalactiae were a positive CMT result,
      teat injury and palpable abnormalities in the udder. Infection with bacteria in
      the SLE group was significantly associated with a SCC of more than 100,000
      cells/ml, a lactation number of more than 2, the right rear quarter (as the
      location of infection) and a positive CMT result.

PMID- 20693506
TI  - Bluetongue virus serotype 8-associated hydranencephaly in two calves in south
      eastern England.

PMID- 20693507
TI  - Mycobacterium intermedium granulomatous pneumonia in a green oropendola
      (Psarocolius viridis).

PMID- 20693511
TI  - Tail injuries in dogs in Great Britain.

PMID- 20693512
TI  - Diseases of racing greyhounds.

PMID- 20693513
TI  - Diagnostic genetic testing requests from owners.

PMID- 20693515
TI  - How different is qualitative health research from qualitative research? Do we
      have a subdiscipline?
AB  - Here, I compare the content, characteristics of participants, and the methods
      used in qualitative health research with qualitative inquiry in general. Special
      problems that occur when conducting research in an institution, with the
      emotional content when participants are ill, in pain, or dying, will be
      discussed. What concerns for the investigator, for the researcher as a person,
      and methodological quandaries occur? The bottom line is: Do we have a
      subdiscipline? Is there a need for a special forum for those practicing
      qualitative health/illness research?

PMID- 20693516
TI  - Women's experience of group prenatal care.
AB  - Group prenatal care (GPNC) is an innovative alternative to individual prenatal
      care. In this longitudinal study we used ethnographic methods to explore African
      American and Hispanic women's experiences of receiving GPNC in two urban clinics.
      Methods included individual, in-depth, semistructured interviews of women and
      group leaders in GPNC, participant observation of GPNC sessions, and medical
      record review. GPNC offered positive experiences and met many of women's
      expressed preferences regarding prenatal care. Six themes were identified, which
      represented separate aspects of women's experiences: investment, collaborative
      venture, a social gathering, relationships with boundaries, learning in the
      group, and changing self. Taken together, the themes conveyed the overall
      experience of GPNC. Women were especially enthusiastic about learning in groups,
      about their relationships with group leaders, and about having their pregnancy
      related changes and fears normalized; however, there were also important
      boundaries on relationships between participants, and some women wished for
      greater privacy during physical examinations.

PMID- 20693517
TI  - Are all perpetrators alike? Comparing risk factors for sexual coercion and
      aggression.
AB  - The present study developed and contrasted predictive models of male nonphysical
      sexual coercion (e.g., verbal pressure or manipulation) and physical sexual
      aggression (e.g., incapacitation, physical force, or threats) using a sample of
      369 incarcerated males to identify shared and unique risk factors for each form
      of sexual perpetration. Results revealed a set of shared risk characteristics
      that predisposed individuals to both sexual coercion and aggression (i.e., belief
      in rape myths, sexual promiscuity, aggressive tendencies, and empathic deficits).
      In addition, findings indicated that whether the offenders engaged in only sexual
      coercion or also used more violent sexually aggressive tactics depended on the
      presence of two sets of traits unique to these forms of perpetration.
      Specifically, sexual coercers tended to possess traits that facilitated the use
      of verbal tactics (i.e., ability to manipulate others and to imagine others'
      emotional reactions). In contrast, sexual aggressors had characteristics that
      could increase their willingness to "cross the line" and resort to more violent
      means to obtain sex from an unwilling partner (i.e., hostility toward women,
      egocentricity, an impulsive disregard for sociolegal proscriptions, and childhood
      emotional abuse). A model of general sexual perpetration that directly contrasted
      sexually coercive and aggressive men was also developed, and hostility toward
      women was identified as the only predictor capable of predicting perpetrator
      group membership. Together, these findings suggest that although sexual coercers
      and aggressors share some underlying risk factors, the etiological patterns of
      these behaviors are distinct and necessitate individual attention by researchers
      and prevention programs.

PMID- 20693518
TI  - Implementing change through education.

PMID- 20693519
TI  - The prospective relationship between binge drinking and physician visits among
      older adults.
AB  - OBJECTIVES: The objectives are to (a) determine if binge drinking is related to
      physician visits and (b) estimate the degree to which the relationship between
      binge drinking and physician visits can be explained by other health
      characteristics. METHOD: Data on a sample of 4,960 older adults (70+ years of age
      in 2002) from the Health and Retirement Study (HRS) were used. Three linear
      regression models estimated the impact of binge drinking on physician visits.
      RESULTS: In the fully adjusted models, binge drinking did have an effect on the
      number of physician visits by older adults, with more frequent binge drinkers
      having fewer physician visits. This negative relationship exists even when
      demographic as well as other current health characteristics are controlled.
      DISCUSSION: The implications of these results are discussed in terms of more
      broadly communicating the risks associated with binge drinking and more
      effectively targeting interventions to older binge drinkers.

PMID- 20693520
TI  - A ''minor'' decision: right to die or manslaughter?

PMID- 20693521
TI  - Decreased neonatal jaundice readmission rate after implementing
      hyperbilirubinemia guidelines and universal screening for bilirubin.
AB  - Readmission rate for neonatal jaundice approximate 10 per 1000 live births. After
      applying hyperbilirubinemia guidelines and universal screening for bilirubin in
      term and near-term newborns, the readmission rate declined significantly from 24
      to 3.7 per 1000 live births. Decreased readmission rate for neonatal jaundice may
      reduce kernicterus rate and health care costs. Further studies are necessary to
      explore these potential benefits.

PMID- 20693522
TI  - A guide for health care practitioners in the assessment of young people's
      capacity to consent to treatment.
AB  - The Health Care Consent Act, 1996, states that every person in Ontario,
      regardless of age, is presumed to be capable of consenting to or refusing medical
      treatment unless he or she is found incapable with respect to a specific
      treatment or plan of treatment. Health care practitioners may find it especially
      challenging to apply the legal test of capacity to young people. As an aid to
      assessment, a guide incorporating both legal and medical perspectives has been
      developed. This article describes the background and context of the development
      of the guide and explains how it helps practitioners to conduct a simpler, more
      focused evaluation of capacity in youth. The guide, along with an introduction
      and comments for parents, is included in an appendix.

PMID- 20693523
TI  - Cardiovascular safety of stimulant medications for pediatric attention-deficit
      hyperactivity disorder.
AB  - Attention-deficit hyperactivity disorder (ADHD) is a common neurobehavioral
      disorder that is often treated with stimulants such as methylphenidate and mixed
      amphetamine salts. Despite their efficacy and long history of use, there is
      concern about their potential for adverse cardiovascular effects in children and
      adolescents. Data from placebo-controlled and open-label extension trials
      published after 2000 were reviewed, and cardiovascular adverse event data were
      compared. Both placebo-controlled and open-label extension trials have repeatedly
      shown stimulant-induced increases in mean blood pressure, heart rate, and QT
      interval in children, adolescents, and adults. Although these increases seem
      relatively minor, their existence raises questions regarding whether stimulants
      could influence the likelihood of sudden death or other serious cardiovascular
      consequences, especially in patients with underlying heart problems. Moreover,
      questions have been raised regarding the necessity of screening patients for
      occult or unrecognized heart problems that are felt to be adversely affected by
      stimulant use. Obtaining a baseline electrocardiogram for any patient starting
      stimulant treatment is reasonable if access to such screening is readily
      available and not too costly.

PMID- 20693524
TI  - Comment on: Increasing incidence of community-associated atypical Clostridium
      difficile disease in children.

PMID- 20693526
TI  - ChIPing the cistrome of PXR in mouse liver.
AB  - The pregnane X receptor (PXR) is a key regulator of xenobiotic metabolism and
      disposition in liver. However, little is known about the PXR DNA-binding
      signatures in vivo, or how PXR regulates novel direct targets on a genome-wide
      scale. Therefore, we generated a roadmap of hepatic PXR bindings in the entire
      mouse genome [chromatin immunoprecipitation (ChIP)-Seq]. The most frequent PXR
      DNA-binding motif is the AGTTCA-like direct repeat with a 4 bp spacer [direct
      repeat (DR)-4)]. Surprisingly, there are also high motif occurrences with spacers
      of a periodicity of 5 bp, forming a novel DR-(5 n+4) pattern for PXR binding. PXR
      binding overlaps with the epigenetic mark for gene activation (histone-H3K4-di
      methylation), but not with epigenetic marks for gene suppression (DNA methylation
      or histone-H3K27-tri-methylation) (ChIP-on-chip). After administering a PXR
      agonist, changes in mRNA of most PXR-direct target genes correlate with increased
      PXR binding. Specifically, increased PXR binding triggers the trans-activation of
      critical drug-metabolizing enzymes and transporters. The mRNA induction of these
      genes is absent in PXR-null mice. The current work provides the first in vivo
      evidence of PXR DNA-binding signatures in the mouse genome, paving the path for
      predicting and further understanding the multifaceted roles of PXR in liver.

PMID- 20693527
TI  - Stimulation of ribosomal frameshifting by antisense LNA.
AB  - Programmed ribosomal frameshifting is a translational recoding mechanism commonly
      used by RNA viruses to express two or more proteins from a single mRNA at a fixed
      ratio. An essential element in this process is the presence of an RNA secondary
      structure, such as a pseudoknot or a hairpin, located downstream of the slippery
      sequence. Here, we have tested the efficiency of RNA oligonucleotides annealing
      downstream of the slippery sequence to induce frameshifting in vitro. Maximal
      frameshifting was observed with oligonucleotides of 12-18 nt. Antisense
      oligonucleotides bearing locked nucleic acid (LNA) modifications also proved to
      be efficient frameshift-stimulators in contrast to DNA oligonucleotides. The
      number, sequence and location of LNA bases in an otherwise DNA oligonucleotide
      have to be carefully manipulated to obtain optimal levels of frameshifting. Our
      data favor a model in which RNA stability at the entrance of the ribosomal tunnel
      is the major determinant of stimulating slippage rather than a specific three
      dimensional structure of the stimulating RNA element.

PMID- 20693528
TI  - Deep sequencing analysis of mutations resulting from the incorporation of dNTP
      analogs.
AB  - Next-generation DNA sequencing technology was used to score >100,000 mutations
      resulting from exposure of a nucleic acid template to a mutagenic dNTP analog
      during a single pass of a DNA polymerase. An RNA template of known secondary
      structure was reverse transcribed in the presence of 8-oxo-dGTP, dPTP or both,
      followed by forward transcription in the presence of standard NTPs. Each mutagen,
      whether used alone or in combination, resulted in a highly characteristic
      mutation profile. Mutations were generated at a mean frequency of 1-2% per
      eligible nucleotide position, but there was substantial variation in the
      frequency of mutation at different positions, with a SD close to the mean. This
      variation was partly due to the identity of the immediately surrounding
      nucleotides and was not significantly influenced by the secondary structure of
      the RNA template. Most of the variation appears to result from idiosyncratic
      features that derive from local sequence context, demonstrating how different
      genetic sequences have different chemical phenotypes.

PMID- 20693529
TI  - The type II restriction endonuclease MvaI has dual specificity.
AB  - The MvaI restriction endonuclease cuts 5'-CC?AGG-3'/5'-CC?TGG-3' sites as
      indicated by the arrows. N4-methylation of the inner cytosines
      (C(m4)CAGG/C(m4)CTGG) protects the site against MvaI cleavage. Here, we show that
      MvaI nicks the G-strand of the related sequence (CCGGG/CCCGG, BcnI site) if the
      inner cytosines are C5-methylated: C(m5)C?GGG/CC(m5)CGG. At M.SssI-methylated
      SmaI sites, where two oppositely oriented methylated BcnI sites partially
      overlap, double-nicking leads to double-strand cleavage (CC(m5)C?GGG/CC(m5)C?GGG)
      generating fragments with blunt ends. The double-strand cleavage rate and the
      stringency of substrate site recognition is lower at the methylation-dependent
      site than at the canonical target site. MvaI is the first restriction
      endonuclease shown to possess, besides the 'normal' activity on its unmethylated
      recognition site, also a methylation-directed activity on a different sequence.

PMID- 20693530
TI  - An engineered mammalian band-pass network.
AB  - Gene expression circuitries, which enable cells to detect precise levels within a
      morphogen concentration gradient, have a pivotal impact on biological processes
      such as embryonic pattern formation, paracrine and autocrine signalling, and
      cellular migration. We present the rational synthesis of a synthetic genetic
      circuit exhibiting band-pass detection characteristics. The components, involving
      multiply linked mammalian trans-activator and -repressor control systems, were
      selected and fine-tuned to enable the detection of 'low-threshold' morphogen
      (tetracycline) concentrations, in which target gene expression was triggered, and
      a 'high-threshold' concentration, in which expression was muted. In silico
      predictions and supporting experimental findings indicated that the key criterion
      for functional band-pass detection was the matching of componentry that enabled
      sufficient separation of the low and high threshold points. Using the circuitry
      together with a fluorescence-encoded target gene, mammalian cells were
      genetically engineered to be capable of forming a band-like pattern of
      differentiation in response to a tetracycline chemical gradient. Synthetic gene
      networks designed to emulate naturally occurring gene behaviours provide not only
      insight into biological processes, but may also foster progress in future tissue
      engineering, gene therapy and biosensing applications.

PMID- 20693531
TI  - High-quality gene assembly directly from unpurified mixtures of microarray
      synthesized oligonucleotides.
AB  - To meet the growing demand for synthetic genes more robust, scalable and
      inexpensive gene assembly technologies must be developed. Here, we present a
      protocol for high-quality gene assembly directly from low-cost marginal-quality
      microarray-synthesized oligonucleotides. Significantly, we eliminated the time-
      and money-consuming oligonucleotide purification steps through the use of
      hybridization-based selection embedded in the assembly process. The protocol was
      tested on mixtures of up to 2000 oligonucleotides eluted directly from
      microarrays obtained from three different chip manufacturers. These mixtures
      containing <5% perfect oligos, and were used directly for assembly of 27 test
      genes of different sizes. Gene quality was assessed by sequencing, and their
      activity was tested in coupled in vitro transcription/translation reactions.
      Genes assembled from the microarray-eluted material using the new protocol
      matched the quality of the genes assembled from >95% pure column-synthesized
      oligonucleotides by the standard protocol. Both averaged only 2.7 errors/kb, and
      genes assembled from microarray-eluted material without clonal selection produced
      only 30% less protein than sequence-confirmed clones. This report represents the
      first demonstration of cost-efficient gene assembly from microarray-synthesized
      oligonucleotides. The overall cost of assembly by this method approaches 5c per
      base, making gene synthesis more affordable than traditional cloning.

PMID- 20693532
TI  - Identification of functional clock-controlled elements involved in differential
      timing of Per1 and Per2 transcription.
AB  - It has been proposed that robust rhythmic gene expression requires clock
      controlled elements (CCEs). Transcription of Per1 was reported to be regulated by
      the E-box and D-box in conventional reporter assays. However, such experiments
      are inconclusive in terms of how the CCEs and their combinations determine the
      phase of the Per1 gene. Whereas the phase of Per2 oscillation was found to be the
      most delayed among the three Period genes, the phase-delaying regions of the Per2
      promoter remain to be determined. We therefore investigated the regulatory
      mechanism of circadian Per1 and Per2 transcription using an in vitro rhythm
      oscillation-monitoring system. We found that the copy number of the E-box might
      play an important role in determining the phase of Per1 oscillation. Based on
      real-time bioluminescence assays with various promoter constructs, we provide
      evidence that the non-canonical E-box is involved in the phase delay of Per2
      oscillation. Transfection experiments confirmed that the non-canonical E-box
      could be activated by CLOCK/BMAL1. We also show that the D-box in the third
      conserved segment of the Per2 promoter generated high amplitude. Our experiments
      demonstrate that the copy number and various combinations of functional CCEs
      ultimately led to different circadian phases and amplitudes.

PMID- 20693533
TI  - Homeotic proteins participate in the function of human-DNA replication origins.
AB  - Recent evidence points to homeotic proteins as actors in the crosstalk between
      development and DNA replication. The present work demonstrates that HOXC13,
      previously identified as a new member of human DNA replicative complexes, is a
      stable component of early replicating chromatin in living cells: it displays a
      slow nuclear dynamics due to its anchoring to the DNA minor groove via the
      arginine-5 residue of the homeodomain. HOXC13 binds in vivo to the lamin B2
      origin in a cell-cycle-dependent manner consistent with origin function; the
      interaction maps with nucleotide precision within the replicative complex. HOXC13
      displays in vitro affinity for other replicative complex proteins; it interacts
      also in vivo with the same proteins in a cell-cycle-dependent fashion. Chromatin
      structure modifying treatments, disturbing origin function, reduce also HOXC13
      origin interaction. The described interactions are not restricted to a single
      origin nor to a single homeotic protein (also HOXC10 binds the lamin B2 origin in
      vivo). Thus, HOX complexes probably contribute in a general, structure-dependent
      manner, to origin identification and assembly of replicative complexes thereon,
      in presence of specific chromatin configurations.

PMID- 20693534
TI  - Dissecting the role of conserved box C/D sRNA sequences in di-sRNP assembly and
      function.
AB  - In all three kingdoms of life, nucleotides in ribosomal RNA (rRNA) are post
      transcriptionally modified. One type of chemical modification is 2'-O-ribose
      methylation, which is, in eukaryotes and archaea, performed by box C/D small
      ribonucleoproteins (box C/D sRNPs in archaea) and box C/D small nucleolar
      ribonucleoproteins (box C/D snoRNPs in eukaryotes), respectively. Recently, the
      first structure of any catalytically active box C/D s(no)RNP determined by
      electron microscopy and single particle analysis surprisingly demonstrated that
      they are dimeric RNPs. Mutational analyses of the Nop5 protein interface
      suggested that di-sRNP formation is also required for the in vitro catalytic
      activity. We have now analyzed the functional relevance of the second interface,
      the sRNA interface, within the box C/D di-sRNP. Mutations in conserved sequence
      elements of the sRNA, which allow sRNP assembly but which severely interfere with
      the catalytic activity of box C/D sRNPs, prevent formation of the di-sRNP. In
      addition, we can observe the dimeric box C/D sRNP architecture with a different
      box C/D sRNP, suggesting that this architecture is conserved. Together, these
      results provide further support for the functional relevance of the di-sRNP
      architecture and also provide a structural explanation for the observed defects
      in catalysis of 2'-O-ribose methylation.

PMID- 20693535
TI  - Stoichiometric incorporation of base substitutions at specific sites in
      supercoiled DNA and supercoiled recombination intermediates.
AB  - Supercoiled DNA is the relevant substrate for a large number of DNA transactions
      and has additionally been found to be a favorable form for delivering DNA and
      protein-DNA complexes to cells. We report here a facile method for
      stoichiometrically incorporating several different modifications at multiple,
      specific, and widely spaced sites in supercoiled DNA. The method is based upon
      generating an appropriately gapped circular DNA, starting from single-strand
      circular DNA from two phagemids with oppositely oriented origins of replication.
      The gapped circular DNA is annealed with labeled and unlabeled synthetic
      oligonucleotides to make a multiply nicked circle, which is covalently sealed and
      supercoiled. The method is efficient, robust and can be readily scaled up to
      produce large quantities of labeled supercoiled DNA for biochemical and
      structural studies. We have applied this method to generate dye-labeled
      supercoiled DNA with heteroduplex bubbles for a Forster resonance energy transfer
      (FRET) analysis of supercoiled Holliday junction intermediates in the lambda
      integrative recombination reaction. We found that a higher-order structure
      revealed by FRET in the supercoiled Holliday junction intermediate is preserved
      in the linear recombination product. We suggest that in addition to studies on
      recombination complexes, these methods will be generally useful in other
      reactions and systems involving supercoiled DNA.

PMID- 20693536
TI  - Coordinated allele-specific histone acetylation at the differentially methylated
      regions of imprinted genes.
AB  - Genomic imprinting is an epigenetic inheritance system characterized by parental
      allele-specific gene expression. Allele-specific DNA methylation and chromatin
      composition are two epigenetic modification systems that control imprinted gene
      expression. To get a general assessment of histone lysine acetylation at
      imprinted genes we measured allele-specific acetylation of a wide range of lysine
      residues, H3K4, H3K18, H3K27, H3K36, H3K79, H3K64, H4K5, H4K8, H4K12, H2AK5,
      H2BK12, H2BK16 and H2BK46 at 11 differentially methylated regions (DMRs) in
      reciprocal mouse crosses using multiplex chromatin immunoprecipitation SNuPE
      assays. Histone acetylation marks generally distinguished the methylation-free
      alleles from methylated alleles at DMRs in mouse embryo fibroblasts and embryos.
      Acetylated lysines that are typically found at transcription start sites
      exhibited stronger allelic bias than acetylated histone residues in general.
      Maternally methylated DMRs, that usually overlap with promoters exhibited higher
      levels of acetylation and a 10% stronger allele-specific bias than paternally
      methylated DMRs that reside in intergenic regions. Along the H19/Igf2 imprinted
      domain, allele-specific acetylation at each lysine residue depended on functional
      CTCF binding sites in the imprinting control region. Our results suggest that
      many different histone acetyltransferase and histone deacetylase enzymes must act
      in concert in setting up and maintaining reciprocal parental allelic histone
      acetylation at DMRs.

PMID- 20693537
TI  - Biophysical and atomic force microscopy characterization of the RNA from
      satellite tobacco mosaic virus.
AB  - Agarose gel electrophoresis, circular dichroism and differential scanning
      calorimetry showed that single-stranded RNA from satellite tobacco mosaic virus
      transforms from a conformationally 'closed state' at 4 degrees C to a more
      conformationally 'open state' at 65 degrees C. The transition is reversible and
      shows no hysteresis. Atomic force microscopy (AFM) allowed visualization of the
      two states and indicated that the conformationally 'closed state' probably
      corresponds to the native encapsidated conformation, and that the 'open state'
      represents a conformation, characterized as short, thick chains of domains, as a
      consequence of the loss of tertiary interactions. Heating from 75 degrees C to 85
      degrees C in the presence of EDTA was necessary to further unravel the 'open'
      conformation RNA into extended chains of lengths >280 nm. Virus exposed to low
      concentrations of phenol at 65 degrees C, extruded RNA as distinctive 'pigtails'
      in a synchronous fashion, and these 'pigtails' then elongated, as the RNA was
      further discharged by the particles. Moderate concentrations of phenol at 65
      degrees C produced complete disruption of virions and only remains of decomposed
      particles and disordered RNA were evident. AFM images of RNA emerging from
      disrupted virions appear most consistent with linear arrangements of structural
      domains.

PMID- 20693538
TI  - Localization of xeroderma pigmentosum group A protein and replication protein A
      on damaged DNA in nucleotide excision repair.
AB  - The interaction of xeroderma pigmentosum group A protein (XPA) and replication
      protein A (RPA) with damaged DNA in nucleotide excision repair (NER) was studied
      using model dsDNA and bubble-DNA structure with 5-{3-[6-(carboxyamido
      fluoresceinyl)amidocapromoyl]allyl}-dUMP lesions in one strand and containing
      photoreactive 5-iodo-dUMP residues in defined positions. Interactions of XPA and
      RPA with damaged and undamaged DNA strands were investigated by DNA-protein
      photocrosslinking and gel shift analysis. XPA showed two maximums of crosslinking
      intensities located on the 5'-side from a lesion. RPA mainly localized on
      undamaged strand of damaged DNA duplex and damaged bubble-DNA structure. These
      results presented for the first time the direct evidence for the localization of
      XPA in the 5'-side of the lesion and suggested the key role of XPA orientation in
      conjunction with RPA binding to undamaged strand for the positioning of the NER
      preincision complex. The findings supported the mechanism of loading of the
      heterodimer consisting of excision repair cross-complementing group 1 and
      xeroderma pigmentosum group F proteins by XPA on the 5'-side from the lesion
      before damaged strand incision. Importantly, the proper orientation of XPA and
      RPA in the stage of preincision was achieved in the absence of TFIIH and XPG.

PMID- 20693539
TI  - Selection of RNA aptamers that bind HIV-1 LTR DNA duplexes: strand invaders.
AB  - RNA that can specifically bind to double-stranded DNA is of interest because it
      might be used as a means to regulate transcription of the target genes. To
      explore possible interactions between RNA and duplex DNA, we selected for RNA
      aptamers that can bind to the long terminal repeats (LTRs) of human
      immunodeficiency virus type 1 DNA. The selected aptamers were classified into
      four major groups based on the consensus sequences, which were found to locate in
      the non-stem regions of the predicted RNA secondary structures, consistent with
      roles in target binding. Analysis of the aptamer consensus sequences suggested
      that the conserved segments could form duplexes via Watson-Crick base-pairing
      with preferred sequences in one strand of the DNA, assuming the aptamer invaded
      the duplex. The aptamer binding sites on the LTR were experimentally determined
      to be located preferentially at these sites near the termini of double-stranded
      target DNA, despite selection schemes that were designed to minimize preferences
      for termini. The results presented here show that aptamer RNAs can be selected in
      vitro that strand-invade at preferred DNA duplex sequences to form stable
      complexes.

PMID- 20693540
TI  - Successful treatment of severe paediatric rheumatic disease-associated macrophage
      activation syndrome with interleukin-1 inhibition following conventional
      immunosuppressive therapy: case series with 12 patients.

PMID- 20693541
TI  - Very early-onset frontotemporal dementia with no family history predicts
      underlying fused in sarcoma pathology.

PMID- 20693542
TI  - Peripheral neuropathy in adult type 1 Gaucher disease: a 2-year prospective
      observational study.
AB  - Type 1 Gaucher disease is currently categorized as non-neuronopathic, although
      recent studies suggest peripheral neurological manifestations. We report
      prevalence and incidence data for peripheral neuropathy and associated conditions
      from a multinational, prospective, longitudinal, observational cohort study in
      patients with type 1 Gaucher disease, either untreated or receiving enzyme
      replacement therapy. The primary outcome parameters were the prevalence and
      incidence of polyneuropathy, evaluated by standardized assessments of
      neurological symptoms and signs, and electrophysiological studies. All diagnoses
      of polyneuropathy were adjudicated centrally. Secondary outcome parameters
      included the prevalence and incidence of mononeuropathy, other neurological or
      electrophysiological abnormalities not fulfilling the criteria for a mono- or
      polyneuropathy and general type 1 Gaucher disease symptoms. Furthermore, a
      literature search was performed to identify all studies reporting on prevalence
      and incidence of polyneuropathy in the general population. One hundred and three
      patients were enrolled [median (range) age: 42 (18-75) years; disease duration:
      15 (0-56) years; 52% female]; 14 (13.6%) were untreated and 89 (86.4%) were on
      enzyme replacement therapy. At baseline, 11 patients [10.7%; 95% confidence
      interval (CI): 5.9-18.3] were diagnosed with sensory motor axonal polyneuropathy.
      Two (1.9%; 95% CI: 0.1-7.2) had a mononeuropathy of the ulnar nerve. The 2-year
      follow-up period revealed another six cases of polyneuropathy (2.9 per 100 person
      years; 95% CI: 1.2-6.3). Patients with polyneuropathy were older than those
      without (P<0.001). Conditions possibly associated with polyneuropathy were
      identified in four patients only, being monoclonal gammopathy, vitamin B(1)
      deficiency, folic acid deficiency, type 2 diabetes mellitus, renal insufficiency,
      alcohol abuse and exposure to toxins related to profession. The 11 cases of
      polyneuropathy found at baseline were confirmed during follow-up. According to
      the literature, the prevalence of polyneuropathy in the general population was
      estimated between 0.09 and 1.3% and the incidence was estimated between 0.0046
      and 0.015 per 100 person-years. Thus, we conclude that the prevalence and
      incidence of polyneuropathy in patients with type 1 Gaucher disease is increased
      compared with the general population.

PMID- 20693543
TI  - Dendritic cell nuclear protein-1, a novel depression-related protein, upregulates
      corticotropin-releasing hormone expression.
AB  - The recently discovered dendritic cell nuclear protein-1 is the product of a
      novel candidate gene for major depression. The A allele encodes full-length
      dendritic cell nuclear protein-1, while the T allele encodes a premature
      termination of translation at codon number 117 on chromosome 5. In the present
      study we investigate whether the two forms of dendritic cell nuclear protein-1
      might act on corticotropin-releasing hormone, which plays a crucial role in the
      stress response and in the pathogenesis of depression. The messenger RNA
      expression of dendritic cell nuclear protein-1 appeared to be increased in the
      laser micro-dissected paraventricular nucleus of patients with depression
      compared with control subjects. Dendritic cell nuclear protein-1 was also found
      to be co-localized with corticotropin-releasing hormone in paraventricular
      nucleus neurons. Moreover, full-length dendritic cell nucleus protein-1 bound to
      and transactivated the promoter of corticotropin-releasing hormone in human
      embryonic kidney 293 cells. We propose that full-length dendritic cell nucleus
      protein-1 may play a role in the pathogenesis of depressive disorders by
      enhancing corticotropin-releasing hormone expression in the hypothalamic
      paraventricular nucleus.

PMID- 20693544
TI  - Morbidity and mortality in heart failure patients treated with cardiac
      resynchronization therapy: influence of pre-implantation characteristics on long
      term outcome.
AB  - AIMS: Cardiac resynchronization therapy (CRT) improves cardiac function, heart
      failure symptoms, and prognosis in selected patients. Many baseline
      characteristics associated with heart failure may influence prognosis after CRT.
      The objective of this study was to evaluate the effect of several baseline
      characteristics in relation to long-term prognosis in heart failure patients
      treated with CRT. METHODS AND RESULTS: A total of 716 consecutive heart failure
      patients treated with CRT were included in an observational registry. All
      available data, including clinical and echocardiographic measurements, were
      analysed in relation to two endpoints: all-cause mortality and a combined
      endpoint of all-cause mortality or major cardiovascular event. Outcome data were
      collected by chart review, device interrogation, and telephone contact. Mean
      follow-up was 25 +/- 19 months. During follow-up, 141 patients (20%) died
      (primary endpoint). Most of these patients (61%) died due to worsening heart
      failure. A total of 214 patients (30%) reached the secondary endpoint. Larger
      left ventricular end-systolic volume, less distance covered in the 6 min walking
      test, poor renal function, more severe heart failure, male gender, presence of
      atrial fibrillation, no posterolateral left ventricular (LV) lead, and no LV
      dyssynchrony were associated with poor prognosis after CRT. CONCLUSION: In this
      large single-centre registry, several baseline clinical and echocardiographic
      characteristics were associated with prognosis after CRT. Worsening heart failure
      was the main cause of death in heart failure patients treated with CRT.

PMID- 20693545
TI  - Dynamic change of mitral apparatus as potential cause of left ventricular outflow
      tract obstruction in hypertrophic cardiomyopathy.
AB  - AIMS: the geometry of the mitral apparatus changes dynamically throughout systole
      and diastole. We investigated how geometric dynamics of the mitral apparatus
      could affect the haemodynamics of the outflow tract in patients with hypertrophic
      cardiomyopathy presenting with systolic anterior motion (HCM(SAM)) using three
      dimensional (3D) echocardiography. METHODS AND RESULTS: we obtained transthoracic
      volumetric images in 21 patients with HCM(SAM) with differing trans-left
      ventricular (LV) outflow tract pressure gradient (PG(LVOT)) and in 23 controls.
      Original software was used to crop the 3D data into 18 radial planes; the mitral
      annulus, leaflets, coaptation point, protruding septum, and papillary muscles
      (PMs) tips were traced in each plane. The data were then reconstructed for 3D
      distance measurements and volumetric assessment. Shorter coaptation-septal
      distance (12 +/- 4 vs. 21 +/- 3 mm, P < 0.001), shorter inter-PM distance (13 +/-
      5 vs. 18 +/- 4 mm, P = 0.02), and larger mitral tenting volume/body surface area
      (TVindex) (2.1 +/- 1 vs. 0.5 +/- 0.3 mL/m(2), P < 0.001) were associated with
      HCM(SAM) vs. control. PG(LVOT) increased with TVindex (r = 0.51, P = 0.01), and
      decreased with coaptation-septal distance(r = -0.83, P < 0.001) and the inter-PM
      distance (r = -0.69, P < 0.001) at mid-systole but not at mid-diastole (all P>
      0.05). In addition, the coaptation-septal distance, TVindex, and inter-PM
      distance correlated each other (all P < 0.05). After adjustment for measures of
      mitral geometric change, the coaptation-septal distance was closely associated
      with PG(LVOT) (beta = -0.73, P < 0.001). CONCLUSION: these findings suggest that
      dynamic geometric changes by interaction of PMs, mitral tenting, and the
      coaptation point at mid-systole may be important contributors to outflow
      obstruction in HCM(SAM).

PMID- 20693546
TI  - Myocardial perfusion echocardiography: a novel use in the diagnosis of sepsis
      induced left ventricular systolic impairment on the intensive care unit.
AB  - Impaired left ventricular systolic function secondary to sepsis can occur in up
      to 20% of patients with septic shock. The electrocardiogram (ECG) and
      echocardiographic changes it produces can be very similar to those occurring
      during acute coronary syndromes (ACS). Myocardial contrast echocardiography (MCE)
      allows assessment of myocardial perfusion. This technique can be performed at the
      bedside of the critically unwell patient. We describe a patient presenting with
      septic shock secondary to pneumonia. While sedated and ventilated in the
      intensive care unit, the patient developed marked ECG changes, a troponin rise
      and widespread left ventricular wall motion abnormality. The clinical picture
      suggested ACS or stress cardiomyopathy was unlikely and was more in keeping with
      a diagnosis of sepsis-induced left ventricular systolic dysfunction. To support
      this, resting and flash impulse MCE was performed which revealed normal perfusion
      in areas of both normal and abnormal wall motion. This suggested that the cardiac
      presentation was more likely to be due to left ventricular impairment secondary
      to sepsis and ACS therapy was discontinued. Pre-discharge ECG and transthoracic
      echocardiogram were normal. Percutaneous coronary angiography 6 weeks later was
      also normal. This is the first described case of MCE being used to aid in the
      decision-making process in distinguishing between ACS, stress cardiomyopathy, and
      left ventricular systolic impairment secondary to sepsis.

PMID- 20693547
TI  - Transseptal puncture using minimally invasive echocardiography during atrial
      fibrillation ablation.
AB  - AIMS: To assess the usefulness of miniature transoesophageal echocardiography
      using a 10 F intracardiac probe (ICE-TEE) for transseptal catheterization during
      atrial fibrillation (AF) ablation. METHODS AND RESULTS: Intracardiac
      echocardiography probe was used transoesophageally in 79 consecutive patients (56
      +/- 11 years, 73% male) referred for AF ablation (60% paroxysmal and 38%
      persistent) to guide transseptal puncture. Transseptal catheterization monitored
      by ICE-TEE was well tolerated and successfully performed in all patients without
      any sedation. No mechanical oesophageal complication was noted. Moreover, the
      mean duration between ICE-TEE probe insertion and successful transseptal puncture
      was 4.5 min and the mean time of ICE-TEE was 10 min. Finally, no tamponade
      occurred during the AF ablation procedure. CONCLUSION: Intracardiac
      echocardiography-TEE is safe and well tolerated for the guidance of transseptal
      catheterization during AF ablation. Moreover, this technique was performed
      without requiring any anaesthesia.

PMID- 20693548
TI  - Cancer care and residents' working hours in oncology and hematology departments:
      an observational real-time study in German hospitals.
AB  - BACKGROUND: Physicians currently working in hematology and oncology wards are
      often frustrated with their working conditions. They express dissatisfaction with
      the working hours, poor organization of work and a low salary compared with the
      burdens of cancer care. However, to date, there have been no real-time
      observational studies to verify these subjective reports. Therefore, this study
      is the first to provide objective data about residents' workload. METHODS: A real
      time task analysis was conducted by individually observing 21 hematology and
      oncology residents at German hospitals. A total of 626 h of observation were
      performed using an Ultra Mobile PC. RESULTS: The residents observed in this study
      worked an average of 9 h 56 min per day, during which time was divided among the
      following activities: 31.20% for internal communication, 22.06% for indirect
      patient care and 10.99% for ward rounds. Per workday residents spent an average
      6.20% of their shift time talking to patients. CONCLUSIONS: This study provides
      the basis for future analyses on physicians' workflow. Some key results may be
      used to recommend measures to improve physicians' work performance and the
      quality of cancer care.

PMID- 20693549
TI  - Clinical analysis of thymic regrowth following chemotherapy in children and
      adolescents with malignant lymphoma.
AB  - OBJECTIVES: Thymic regrowth following chemotherapy has typical clinical and
      imaging manifestations that can be used to diagnose it prior to pathological
      diagnosis. We investigated methods for diagnosing thymic regrowth following
      chemotherapy with non-invasive methods. METHODS: Our study included 26 children
      and adolescents with thymic regrowth following chemotherapy for malignant
      lymphoma. Computed tomography scans were routinely performed for follow-up
      observations. After the emergence of new mediastinal masses, patients either
      underwent Fluorine-18 fluorodeoxyglucose-positron emission tomography scans to
      identify the characteristics of the mass, or were closely followed up. RESULTS:
      Thymic regrowth occurred 1-12 months after the last chemotherapy (mean, 4
      months). Computed tomography mostly revealed diffusely enlarged thymic
      parenchymatous tissues that maintained normal thymic morphology. Computed
      tomography values were 36.72 +/- 9.48 Hu and increased by 5.56 +/- 2.62 Hu in
      contrast enhancement. The mean volume of the mass was 19.2 cm(3). Twenty patients
      underwent positron emission tomography; among them, five (25%) showed no intake
      of Fluorine-18 fluorodeoxyglucose in the anterior mediastinal mass, and 15 (75%)
      showed radioactivity distribution in the mass with a mean standardized uptake
      value of 2.7; the shape was regular and radioactivity distribution was uniform.
      The mean follow-up duration was 40 months and all patients achieved disease-free
      survival. CONCLUSIONS: In the absence of pathological diagnosis, thymic regrowth
      following chemotherapy can be diagnosed by clinical features combined with
      characteristic manifestations in computed tomography and positron emission
      tomography scans.

PMID- 20693550
TI  - The severity of phenotype linked to SUCLG1 mutations could be correlated with
      residual amount of SUCLG1 protein.
AB  - BACKGROUND: Succinate-CoA ligase deficiency is responsible for encephalomyopathy
      with mitochondrial DNA depletion and mild methylmalonic aciduria. Mutations in
      SUCLA2, the gene encoding a beta subunit of succinate-CoA ligase, have been
      reported in 17 patients until now. Mutations in SUCLG1, encoding the alpha
      subunit of the enzyme, have been described in two pedigrees only. METHODS AND
      FINDINGS: In this study, two unrelated patients harbouring three novel pathogenic
      mutations in SUCLG1 were reported. The first patient had a severe disease at
      birth. He was compound heterozygous for a missense mutation (p.Pro170Arg) and a
      c.97+3G>C mutation, which leads to the complete skipping of exon 1 in a minigene
      expression system. The involvement of SUCLG1 was confirmed by western blot
      analysis, which showed absence of SUCLG1 protein in fibroblasts. The second
      patient has a milder phenotype, similar to that of patients with SUCLA2
      mutations, and is still alive at 12 years of age. Western blot analysis showed
      some residual SUCLG1 protein in patient's fibroblasts. CONCLUSIONS: Our results
      suggest that SUCLG1 mutations that lead to complete absence of SUCLG1 protein are
      responsible for a very severe disorder with antenatal manifestations, whereas a
      SUCLA2-like phenotype is found in patients with residual SUCLG1 protein.
      Furthermore, it is shown that in the absence of SUCLG1 protein, no SUCLA2 protein
      is found in fibroblasts by western blot analysis. This result is consistent with
      a degradation of SUCLA2 when its heterodimer partner, SUCLG1, is absent.

PMID- 20693551
TI  - Population-based prevalence of uveitis in Southern India.
AB  - PURPOSE: To estimate the prevalence of uveitis in rural Tamil Nadu, India.
      METHODS: Cluster sampling identified a population-based sample of 5150 persons
      ages 40 years and older, representative of three districts in Tamil Nadu, India.
      Each received a comprehensive dilated ocular examination by an ophthalmologist,
      and results were registered on forms requiring responses about the presence of
      ocular inflammatory signs and inflammatory diagnoses. Potential uveitis cases
      were confirmed by consensus of two uveitis specialists, upon review of study and
      medical records. Crude prevalence rates and prevalence rates age-adjusted to
      reflect the 2001 Tamil Nadu census population were calculated. RESULTS: Crude and
      age-adjusted prevalence rates for endogenous uveitis were 310/100,000 and
      317/100,000. The corresponding rates for all ocular inflammation were 450 and
      467/100,000. Males tended to have a greater prevalence than females in this
      population, and older persons tended to have higher prevalence than younger
      persons. The majority of cases of posterior uveitis and infectious
      endophthalmitis were visually compromised, but few among the cases of other forms
      of ocular inflammation were visually impaired. CONCLUSIONS: The results suggest
      that nearly one in 200 persons in rural, South India has been affected by ocular
      inflammation in at least one eye by mid to late adulthood, about one in 330 if
      cases related to surgery or trauma are not included. Postsurgical endophthalmitis
      and posterior uveitis were associated with a high rate of vision loss. These
      results indicate that uveitis is an important cause of ocular morbidity and of
      vision loss in this population.

PMID- 20693552
TI  - Dark adaptation in vitamin A-deficient adults awaiting liver transplantation:
      improvement with intramuscular vitamin A treatment.
AB  - BACKGROUND/AIMS: Although vitamin A deficiency is common in chronic liver
      disease, limited data exist on impairment of dark adaptation and response to
      therapy. The aims were (1) to assess dark adaptation in patients, (2) to assess
      the relationship between dark adaptation and vitamin A status, zinc and Child
      Pugh score, (3) to compare perceived and measured dark adaptation and (4) to
      assess the dark adaptation response to intramuscular vitamin A. METHODS: This was
      a prospective study of 20 patients (alcoholic liver disease 10, other parenchymal
      diseases six, cholestatic diseases four) awaiting liver transplantation.
      Selection was based on low serum retinol. There were 15 age-matched controls.
      Dark adaptation was measured with a SST-1 dark adaptometer and perception by
      questionnaire. Eight patients received 50, 000 IU of retinyl palmitate, and dark
      adaptation was repeated at 1 month. RESULTS: Forty per cent of patients had
      impaired dark adaptation. Patients with alcoholic liver disease were more
      impaired than those with other parenchymal diseases (p=0.015). No relationship
      was found between dark adaptation and the biochemical indicators or Child-Pugh
      score. Seventy-five per cent of patients with impairment did not perceive a
      problem. After intervention, light of half the previous intensity could be seen
      (p=0.05). CONCLUSIONS: Dark-adaptation impairment was common, was worse in
      alcoholic liver disease, was largely not appreciated by the patients and improved
      with vitamin A treatment.

PMID- 20693553
TI  - Management of keratoconus: current scenario.
AB  - Keratoconus is an ectatic corneal dystrophy and is a leading indication for
      corneal transplantation surgery worldwide. The disease was first described in
      detail more than 150 years ago by Dr John Nottingham, but the understanding of
      the disease and its management have undergone significant changes over the last
      few decades. Corneal specialists have adopted new techniques and technologies for
      the effective management of keratoconus, while adhering to the age-old concepts
      of contact lens fitting and penetrating keratoplasty. Lamellar keratoplasty has
      been revived with improved outcomes and devices such as intracorneal ring
      segments are being used to treat cases of early keratoconus effectively. This
      review article discusses the current scenario on the surgical as well as non
      surgical management of keratoconus with a focus on the established, novel and
      emerging treatment modalities.

PMID- 20693554
TI  - Donor cell density and endothelial keratoplasty.

PMID- 20693555
TI  - A clinicopathological correlation of 67 eyes primarily enucleated for advanced
      intraocular retinoblastoma.
AB  - AIMS: To correlate the clinical and histopathological findings of eyes primarily
      enucleated for advanced intraocular retinoblastoma. METHODS: In a retrospective
      study, the authors identified patients primarily enucleated for advanced
      intraocular retinoblastoma. The authors retrieved patient demographics, clinical
      findings, subsequent treatments and outcomes, and reviewed the histopathology of
      each eye for invasion of the anterior chamber, iris, ciliary body, choroid,
      sclera and optic nerve, and extraocular extension. The authors used the Fisher
      exact, exact Jonkheere-Terpstra, exact Wilcoxon rank sum and Kruskal-Wallis
      statistical tests (p<0.05) to study associations between clinical and
      histopathological findings. RESULTS: The authors identified 67 eyes of 67
      patients (33 males) primarily enucleated for retinoblastoma between March 1997
      and January 2008. Corneal diameter, intraocular pressure and Reese-Ellsworth
      Classification had no significant association with invasive disease. The
      International Classification, however, was associated with optic nerve (p=0.026),
      choroid (p<0.001), ciliary body (p=0.002), iris (p=0.002), anterior chamber
      (p=0.025) and scleral (p<0.001) invasion. Eyes classified as International
      Classification Group E were more likely to have invasion of these sites and have
      more severe optic-nerve invasion. CONCLUSIONS: Corneal diameter, intraocular
      pressure and Reese-Ellsworth Classification do not correlate with
      histopathological evidence of invasive retinoblastoma. Eyes classified as
      International Classification Group E are more likely to have elevated intraocular
      pressure, invasion of the anterior chamber, uveal tract, optic nerve and sclera.
      The findings warrant primary enucleation with meticulous histopathological
      examination of such eyes prior to any adjuvant therapy.

PMID- 20693556
TI  - Clinical characteristics of hydroxychloroquine retinopathy.
AB  - AIMS: To assess the characteristics and outcomes of patients with
      hydroxychloroquine retinopathy and to review the current screening guidelines.
      METHODS: Retrospective chart review of patients diagnosed as having
      hydroxychloroquine retinopathy at our institution between 2004 and 2008. RESULTS:
      All seven patients were women. While every patient received 400 mg of
      hydroxychloroquine per day, every patient exceeded the recommended daily dosage
      allowance (6.5 mg/kg/day). The mean daily dose of hydroxychloroquine was 8.2
      mg/kg/day (range: 6.8-13.6 mg/kg/day). The mean duration of usage was 16.3 years
      (range: 8.5-30 years), and the mean cumulative dose was 2377 g (range: 1241-4380
      g). The mean visual acuity at presentation was 20/30, but all patients exhibited
      significant visual-field defects. Colour vision was impaired in six patients.
      Four patients exhibited granular hyperpigmentation in the central macula, and
      three had a bull's eye appearance. The mean follow-up time was 21 months. The
      visual outcomes remained stable for every patient except for one patient who
      experienced an improvement in visual function after drug cessation. CONCLUSIONS:
      Hydroxychloroquine retinopathy, although rare, still exists despite current
      screening guidelines. The authors recommend that physicians dose
      hydroxychloroquine according to lean body weight and that they use risk
      stratification to guide their screening regimens.

PMID- 20693557
TI  - Ocular manifestations of the antiphospholipid syndrome.
AB  - Antiphospholipid syndrome (APS) is an autoimmune disease characterised by a
      heterogenous group of antibodies directed against negatively charged
      phospholipids including antiphospholipid antibodies (aPL), anticardiolipin
      antibodies (aCL) and beta-2 glycoprotein I (abeta-2-GP1). The major features of
      this disorder include arterial and venous thrombosis and recurrent fetal loss.
      The vasculature of the eye is frequently involved and may be the presenting
      manifestation. A diagnosis of APS should be considered in a young patients
      without traditional thromboembolic risk factors presenting with ocular vaso
      occlusive disease. Management of these patients involves a team-approach with a
      haematologist/oncologist or rheumatologist to manage the coagulation status of
      these patients to prevent further systemic vascular occlusions.

PMID- 20693558
TI  - Cross-linked actin networks (CLANs) are present in lamina cribrosa cells.
AB  - AIMS: A study was undertaken to determine and compare the F-actin staining
      patterns in the cells of the lamina cribrosa (LC) of normal, dexamethasone (DEX)
      treated and glaucomatous dissected tissue and cell cultures. METHODS: About 30
      dissected donor eyes and nine cell lines provided the human specimens; 25 eyes
      and 20 primary cell cultures provided the bovine material. Appropriate samples
      were exposed to 1*10-7 M DEX for up to 14 days. LC tissue and cells were stained
      with Phalloidin-Alexa 488 to identify F-actin, and all samples were examined by
      confocal or epifluorescent microscopy. RESULTS: Both in the LC tissue and LC cell
      cultures the dominant actin arrangement was bundles of stress fibres. However,
      cross-linked actin networks (CLANs) were identified in the tissue and in culture.
      These were markedly increased by steroid treatment and were particularly large
      and abundant in cultures from glaucoma donors. CLANs were not associated with
      optic nerve head astrocytes. CONCLUSIONS: The presence of abundant stress fibres
      in situ and in vitro highlights the biomechanical contribution of LC cells.
      However, the identification of CLANs in these cells shows that they are not
      exclusive to the trabecular meshwork, the only other place they have been found,
      and may have a role in glaucoma pathology.

PMID- 20693559
TI  - Imaging of blebs after phacotrabeculectomy with Ologen collagen matrix implants.
AB  - OBJECTIVE: To analyse blebs of phacotrabeculectomies performed with Ologen
      collagen implants (ProTop & MediKing, Taipei, Taiwan) and to compare these with
      blebs of mitomycin C (MMC)-augmented phacotrabeculectomies. METHODS: 33
      participants underwent phacotrabeculectomy with Ologen implants, and 33 controls
      underwent phacotrabeculectomy with MMC. Blebs were analysed for height and area
      using anterior segment optical coherence tomography (ASOCT) at 30, 60 and 90 days
      after surgery and were also graded clinically with the Moorfields bleb grading
      system (MBGS) 60 days after surgery. RESULTS: With ASOCT, there was no difference
      in mean bleb height at 30 and 60 days, but at 90 days, bleb height was lower in
      the Ologen group (Ologen vs MMC, 0.74+/-0.20 vs 1.00+/-0.28 mm, p<0.001). There
      was no difference in mean bleb area at 30, 60 or 90 days. Mean reduction in
      intraocular pressure at 90 days was greater in the MMC group (Ologen vs MMC,
      2.18+/-4.93 vs 8.00 +/-7.60 mm Hg, p<0.001). At 90 days, the Ologen implants were
      visible in ASOCT images in 13 (39.4%) of 33 participants. With the Moorfields
      bleb grading system at 60 days, there was no difference in maximal bleb area
      score between the groups, but bleb height score was lower (Ologen vs MMC, 1.53+/
      0.51 vs 1.81+/-0.59, p=0.05) and central bleb vascularity score was higher in the
      Ologen group (3.88+/-0.55 vs 2.91+/-0.59, p<0.001). CONCLUSIONS: Within 3 months
      of surgery, mean bleb height was lower in the Ologen blebs compared with the MMC
      blebs. The Ologen implants had not degraded in a third of eyes.

PMID- 20693560
TI  - 'Staircase' square-wave jerks in early Parkinson's disease.
AB  - BACKGROUND/AIMS: Visually guided saccades and gaze-fixation ability were recorded
      in patients with early Parkinson's disease (PD). METHODS: Magnetic search coil
      system was used to measure horizontal and vertical eye positions. RESULTS:
      'Staircase' visually guided saccades (multiple hypometric saccades separated by
      an intersaccadic interval) and 'staircase' square-wave jerks (SWJ) were present
      in all patients. The SWJ amplitude (total amplitude of the series of hypometric
      saccades comprising the SWJ) was abnormally large (mean 2 degrees ). SWJ
      frequency was also abnormally high (50-70 intrusions/min). CONCLUSION: Loss of
      dopaminergic neurons in the substantia nigra pars compacta leading to phasic
      excitation of the substantia nigra pars reticulata and, in turn, phasic
      inhibition of the superior colliculus (SC), may account for 'staircase' visually
      guided saccades in these patients. This mechanism, however, does not explain
      abnormally large SWJ, which in the traditional view results from decreased
      inhibition upon SC. The abnormally large SWJ could be due to a compensatory
      increase in frontal eye field activity secondary to the increased inhibition upon
      the SC. Abnormally large and frequent SWJ are often used clinically to
      distinguish multi-system atrophy from idiopathic PD. Our study, however, suggests
      that idiopathic PD cannot be excluded if the patient has large-amplitude SWJ.

PMID- 20693561
TI  - Sebaceous gland carcinoma of the eyelid masquerading as a cutaneous horn in Li-
      Fraumeni syndrome.

PMID- 20693562
TI  - Pressure-cornea-vascular index (PCVI) for predicting disease progression in
      normal tension glaucoma.
AB  - BACKGROUND: It has been shown that the pressure-to-cornea index (PCI), which
      estimates the relative effects of intraocular pressure (IOP) and central corneal
      thickness (CCT), may differentiate between glaucoma and non-glaucoma states. The
      authors investigated the utility of the pressure-cornea-vascular index (PCVI) in
      predicting field-progression in patients with normal tension glaucoma (NTG).
      METHODS: PCVI was constructed from PCI (maximum IOP/CCT(3)) extended with risk
      factors identified as associated with field-progression in a prospective NTG
      cohort. Receiver operator characteristics and area under the curve (AUC) of a
      range of constructs were calculated to arrive at an optimal PCVI. RESULTS: 415
      eyes from 415 NTG subjects (184 field-progressed and 231 field-stable) with 3
      years of follow-up were analysed. The construct PCVI=(maximum pretreatment office
      IOP * age at presentation * vertical cup-to-disc ratio at presentation * (1.5 if
      presence of systemic hypertension; 2.5 if presence of disc haemorrhage; 3.5 if
      presence of both; 1.0 if none))/(CCT(3)*100) (CCT in mm) gave the highest AUC at
      0.71 (95% CI 0.66 to 0.76, p<0.001). The mean PCVI were 113.1+/-76.8 and 69.7+/
      39.7 for progressed and stable NTG groups, respectively (p<0.001). CONCLUSION:
      PCVI may be useful for predicting progression in NTG with a satisfactory AUC
      comparable to established scoring systems in neurovascular medicine. Validation
      of PCVI in other NTG cohorts, preferably of different ethnicity, is necessary.
      Trial registration number NCT00321386.

PMID- 20693563
TI  - Health-related quality of life measures (HRQoL) in patients with amblyopia and
      strabismus: a systematic review.
AB  - BACKGROUND/AIMS: Health-related quality of life (HRQoL) measures are used in
      healthcare to help inform clinical decision-making and policy-making decisions. A
      number of disease-specific or condition-specific measures have been developed and
      applied in ophthalmology; however, their use in the specific fields of amblyopia
      and strabismus are not as established. The purpose of this study is to identify
      and discuss specific HRQoL instruments that may be used in the investigation and
      management of patients with amblyopia and/or strabismus. METHODS: A systematic
      literature review was undertaken in November 2009. The electronic databases of
      AMED (Allied and Complementary Medicine: 1985 to November 2009), the British
      Nursing Index and Archive (1985 to October 2009), Ovid Medline In-Process and
      Other Non-Indexed Citations and Ovid Medline (1950 to present) and PsycINFO (1806
      to November Week 1 2009) were searched. No language restrictions were applied to
      the search. RESULTS: Four instruments were identified: the Amblyopia and
      Strabismus Questionnaire (A&SQ), the Amblyopia Treatment Index (ATI), the Adult
      Strabismus Questionnaire (AS-20) and the Intermittent Exotropia Questionnaire
      (IXTQ). CONCLUSION: The use of HRQoL measures in patients with amblyopia and/or
      strabismus is a developing area. Further research is necessary to determine the
      impact of issues such as diplopia and poor cosmesis upon patient groups, and to
      determine the influence of ethnicity and parental reporting in these patients.

PMID- 20693564
TI  - Topical 1% 5-fluorouracil in ocular surface squamous neoplasia: a long-term
      safety study.
AB  - BACKGROUND/AIMS: The aim of this study was to evaluate the long-term corneal
      toxicity of topical chemotherapy with 1% 5-fluorouracil (5-FU) as a sole or
      adjuvant treatment of ocular surface squamous neoplasia (OSSN). METHODS: Forty
      one consecutive cases of OSSN were included in this prospective study. Patients
      underwent topical chemotherapy with 1% 5-FU four times/day for 4&emsp14;weeks
      (one course). Adjunctive courses were repeated until clinical and cytological
      tumour regression. Clinical confocal microscopy was used to check for 5-FU long
      term corneal toxicity. RESULTS: Mean follow-up was 89.7+/-14.4&emsp14;months
      (range 63-122&emsp14;months). Twenty-two patients (53.7%) underwent topical 5-FU
      as a sole treatment, and 19 patients (46.3%) as adjuvant and/or debulking
      therapy. The mean number of 5-FU cycles was 1.9 (range 1-5 cycles). Three tumours
      (7.3%) treated with 5-FU alone recurred during follow-up. Recurrences were
      successfully treated with additional 5-FU courses. Clinical confocal microscopy
      showed no long-term difference between the treated eye and fellow (control) eye
      in: endothelial cells count, pleomorphism and polymegatism, anterior stromal
      keratocyte density, sub-basal nerve plexus fibre number, density, and beadings
      and central cornea epithelium thickness (p=NS). CONCLUSION: Topical 5-FU, as a
      sole or combined therapy, must be considered a long-term safe and effective
      treatment for patients affected by OSSN.

PMID- 20693565
TI  - Intravitreal bevacizumab for retinal vein occlusion and early growth of
      epiretinal membrane: a possible secondary effect?
AB  - AIMS: To report the early development of epiretinal membranes (ERM) in eyes with
      retinal vein occlusions (RVO) treated with intravitreal bevacizumab and to
      describe possible mechanisms that may be involved in the growth and contraction
      of these lesions. METHODS: Retrospective and interventional study that included
      25 eyes of 25 patients with RVO (16 eyes with central retinal vein occlusion and
      nine eyes with branch retinal vein occlusion). After an initial 2.5mg/0.1ml
      intravitreal bevacizumab injection all patients were followed-up every 6 weeks.
      Re-treatments were based on visual acuity and optical coherence tomography
      findings. Results Twenty-five eyes were treated with bevacizumab and followed for
      8.3 (range 4.5-13.5) months. Four eyes developed an ERM within 6-7weeks after the
      administration of bevacizumab. ERM was not associated with further deterioration
      of visual acuity or metamorphopsia in these patients. A rebound of macular oedema
      was observed in one patient with ERM and in two other patients. No other side
      effects were observed. CONCLUSIONS: Intravitreal bevacizumab may be associated
      with an early growth of ERM in eyes with RVO, although a causative relationship
      cannot be established. Future randomised clinical trials are necessary to
      determine the efficacy and safety profile of this novel therapy.

PMID- 20693567
TI  - Defining osteopathic medicine: can you put your finger on it?

PMID- 20693566
TI  - GIP increases human adipocyte LPL expression through CREB and TORC2-mediated
      trans-activation of the LPL gene.
AB  - GIP (glucose-dependent insulinotropic polypeptide) is a gastrointestinal hormone
      that regulates pancreatic islet function. Additionally, emerging evidence
      suggests an important physiological role for GIP in the regulation of adipocyte
      metabolism. In previous studies on the lipogenic effects of GIP, it was shown to
      increase adipocyte lipoprotein lipase (LPL) activity in both differentiated 3T3
      L1 cells and human adipocytes through a pathway involving activation of protein
      kinase B (PKB)/Akt. In the current study, we examined the effects of GIP on LPL
      gene expression. GIP in the presence of insulin increased LPL gene expression in
      human adipocytes and LPL promoter activity in GIP receptor-expressing HEK-293
      cells, and both effects were greatly reduced by the transcription inhibitor
      actinomycin D. Subsequent studies established that GIP increased phosphorylation
      of Serine 133 in cAMP-response element binding protein (CREB) and the nuclear
      localization of cAMP-responsive CREB coactivator 2 (TORC2) through a pathway
      involving phosphatidylinositol 3-kinase (PI3-K), PKB, and AMP-activated protein
      kinase (AMPK). However, in the presence of insulin, GIP failed to activate the
      cAMP/PKA pathway. Knockdown of CREB and TORC2 using RNA interference reduced LPL
      expression, supporting a functional regulatory role. GIP-induced phospho-CREB and
      TORC2 were shown to bind to a cAMP-response element (-II) site in the human LPL
      promoter and GIP increased protein-protein interactions of these two factors. The
      lipogenic effects of GIP in the presence of insulin are therefore at least
      partially mediated by upregulation of adipocyte LPL gene transcription through a
      pathway involving PI3-K/PKB/AMPK-dependent CREB/TORC2 activation.

PMID- 20693568
TI  - Stable angina pectoris: what does the current clinical evidence tell us?
AB  - Coronary artery disease is the leading cause of death in the United States. The
      combination of noninvasive cardiovascular testing and invasive cardiac procedures
      accounts for a substantial portion of the yearly healthcare expenditure in the
      United States. Although the diagnosis of ischemically-driven chest pain may
      appear to be simple and straightforward, it often takes an astute clinician to
      confirm that clinically significant coronary artery blockage is the cause of a
      patient's chest pain. Cardiovascular research has provided convincing evidence
      that aggressive treatment of hypertension and hyperlipidemia--along with a
      management plan, based on the patient's combined risk factor profile, that
      includes blood glucose assessment, tobacco cessation, weight loss, healthy eating
      choices, and consistent aerobic exercise--must be provided to achieve optimal
      care for our patients. Over the ensuing decade, we will likely continue to see a
      shift away from routine percutaneous treatment of coronary lesions in favor of an
      aggressive assessment of a patient's cardiac risk profile followed by a treatment
      plan centered on active patient involvement including appropriate lifestyle
      changes and selective medications.

PMID- 20693569
TI  - Characteristics of pediatric patients seen in medical school-based osteopathic
      manipulative medicine clinics.
AB  - CONTEXT: Manual medicine--specifically osteopathic manipulative treatment (OMT)-
      is commonly used in treating patients aged 18 years or younger. However, no
      published reports have described characteristics of this patient population or
      the conditions for which OMT is used with these patients. To better counsel
      parents, train physicians and other healthcare providers, and prioritize
      research, an improved understanding of the use of OMT in children is needed.
      OBJECTIVE: To characterize pediatric patients and their conditions as seen in a
      medical school-based osteopathic manipulative medicine clinic. STUDY DESIGN:
      Retrospective analysis of administrative data on the use of OMT. SETTING: Faculty
      osteopathic manipulative medicine specialty clinics associated with the
      University of New England College of Osteopathic Medicine. PATIENTS: Data were
      analyzed from patients seen in the clinics from January 1, 2007, through December
      31, 2007, if they were younger than 19 years at their first visit during that
      period. OUTCOMES MEASURES: Factors included in the data analysis were patient age
      at first visit, age at time of visit, number of visits during the study period,
      types of clinical diagnoses, and visits with nonmusculoskeletal diagnoses.
      RESULTS: A total of 407 patients generated 1500 clinic visits. Data showed a mean
      of 3.7 visits per patient (25th-75th percentiles = 2-5 visits) during the 1-year
      study period. The mean age at the first clinic visit was 7 years, 3 months, with
      the 25th-to-75th percentile being 1 year, 9 months, to 12 years, 3 months. Clinic
      visits by age group (ie, age at time of visit) as percentages of total visits
      were as follows: 0 to 11 months, 13.7%; 1 to 4 years, 33.3%; 5 to 12 years,
      28.9%, older than 12 years, 24.2%. Diagnoses provided in visits covered a wide
      variety of common pediatric conditions. For the entire study population, 43.5% of
      visits included nonmusculoskeletal diagnoses. The percentages of visits with
      nonmusculoskeletal diagnoses for each age group were as follows: 0 to 11 months,
      33.7%; 1 to 4 years, 64.0%; 5 to 12 years, 48.8%; older than 12 years, 17.7%.
      CONCLUSION: Pediatric patients seen in the faculty osteopathic manipulative
      medicine specialty clinic included the entire pediatric age range and a wide
      range of common pediatric conditions. A substantial number of visits involved
      treatment for nonmusculoskeletal conditions. Further investigation is needed to
      determine if the patient sample of the present study is representative of other
      clinical settings or geographic regions.

PMID- 20693570
TI  - Using one question to identify women at risk for an alcohol-exposed pregnancy.
AB  - CONTEXT: Consumption of 8 alcoholic drinks per week or 5 alcoholic drinks on one
      occasion by a pregnant woman can affect the developing fetus. However, it can be
      difficult to determine which patients are at risk. OBJECTIVE: To evaluate how
      well the answer to a single question about binge drinking could help identify
      women at risk of an alcohol-exposed pregnancy (AEP). METHODS: Using data from a
      study of methods to prevent AEPs, the authors compared the efficacy of self
      reported answers to a screening question about binge drinking (5 or more standard
      drinks on one occasion) within the past 90 days with answers to a question about
      drinking quantity (weekly consumption of 8 or more standard drinks) within the
      past 90 days. RESULTS: The participants were 354 women of childbearing age who
      met screening criteria for being at risk of an AEP. The binge question was
      answered positively by 346 women (97.7%) at risk, while only 209 women (59.0%)
      reported that they drank 8 or more drinks in a week. CONCLUSION: A single
      question about binge drinking can effectively and quickly identify the majority
      of women at risk of an AEP.

PMID- 20693571
TI  - Methods and implications of limiting resident duty hours.
AB  - CONTEXT: Current limitations on residency duty hours came about after the death
      of a patient in 1984 in a New York City hospital. This tragedy served as the
      catalyst for a new public awareness and subsequent change in philosophy regarding
      resident duty hours, fatigue factors, and risks to patients from the long and
      tedious shifts of residency. However, it has proven difficult to limit resident
      physician duty hours. OBJECTIVE: To analyze the impact of resident duty hour
      limitation (RDHL) implementation on residents, faculty, and patients. METHODS:
      The authors conducted a survey of faculty and resident attitudes and experiences
      regarding RDHLs in the graduate medical education department at Arrowhead
      Regional Medical Center (ARMC) in Colton, California. They also conducted a
      review of the literature on faculty and resident attitudes and experiences before
      and after implementation of RDHLs. RESULTS: Of 60 surveys sent to ARMC faculty
      members in 2009, 12 (20.0%) were returned. Of 140 surveys sent to ARMC residents,
      96 (68.6%) were returned. The survey results and literature review indicated that
      most faculty physicians initially believed that decreasing resident duty hours
      would limit the time available to residents for educational experiences and
      participation in treatment procedures, operations, and consultations. In
      addition, faculty initially believed that fewer training hours would diminish the
      quality of residents' educational experiences. Residents also expected negative
      outcomes from RDHLs. However, statistical data on actual outcomes revealed that
      residency programs are not adversely affected by limiting resident work hours to
      80 hours per week. Furthermore, benefits of RDHLs appear to include improved
      patient care and well-rounded and psychologically balanced residents. CONCLUSION:
      A survey and literature review revealed a number of benefits of RDHLs. It is
      unclear, however, whether additional limitations of resident work hours are
      necessary or could accommodate the growing amount of information and skills that
      are required to become a competent physician.

PMID- 20693572
TI  - Re: Empowering patients during insulin initiation: a real-world approach.

PMID- 20693573
TI  - How to avoid a heart attack: putting it all together.

PMID- 20693574
TI  - New COMLEX-USA-to-USMLE conversion formula needed.

PMID- 20693575
TI  - cAMP sensitivity of HCN pacemaker channels determines basal heart rate but is not
      critical for autonomic rate control.
AB  - BACKGROUND: HCN channels activate the pacemaker current I(f), which is thought to
      contribute significantly to generation and regulation of heart rhythm. HCN4
      represents the dominant isotype in the sinoatrial node and binding of cAMP was
      suggested to be necessary for autonomic heart rate regulation. METHODS AND
      RESULTS: In a candidate gene approach, a heterozygous insertion of 13 nucleotides
      in exon 6 of the HCN4 gene leading to a truncated cyclic nucleotide-binding
      domain was identified in a 45-year-old woman with sinus bradycardia. Biophysical
      properties determined by whole-cell patch-clamp recording of HEK293 cells
      demonstrated that mutant subunits (HCN4-695X) were insensitive to cAMP.
      Heteromeric channels composed of wild-type and mutant subunits failed to respond
      to cAMP-like homomeric mutant channels, indicating a dominant-negative
      suppression of cAMP-induced channel activation by mutant subunits. Pedigree
      analysis identified 7 additional living carriers showing similar clinical
      phenotypes, that is, sinus node dysfunction with mean resting heart rate of
      45.9+/-4.6 bpm (n=8) compared with 66.5+/-9.1 bpm of unaffected relatives (n=6;
      P<0.01). Clinical evaluation revealed no ischemic or structural heart disease in
      any family member. Importantly, mutant carriers exhibited normal heart rate
      variance and full ability to accelerate heart rate under physical activity or
      pharmacological stimulation. Moreover, mutant carriers displayed distinctive
      sinus arrhythmias and premature beats linked to adrenergic stress. CONCLUSIONS:
      In humans, cAMP responsiveness of I(f) determines basal heart rate but is not
      critical for maximum heart rate, heart rate variability, or chronotropic
      competence. Furthermore, cAMP-activated I(f) may stabilize heart rhythm during
      chronotropic response.

PMID- 20693576
TI  - Clinical characteristics of patients with persistent atrial fibrillation
      successfully treated by left atrial ablation.
AB  - BACKGROUND: We sought to characterize patients with persistent atrial
      fibrillation (AF) who were successfully treated by ablation targeting the left
      atrium (LA). METHODS AND RESULTS: Ninety-three patients (58+/-10 years, 79 male)
      undergoing ablation of persistent AF were studied. During the first procedure,
      ablation was performed in the LA and coronary sinus, consisting of pulmonary vein
      isolation, linear ablation, and electrogram-based ablation. During follow-up
      after the first procedure, 35 patients (38%) remained free from tachyarrhythmias,
      27 patients (29%) had atrial tachycardia, and 31 patients (33%) had AF. Duration
      of persistent AF according to medical history and whether AF was terminated by
      ablation were associated with the outcome (P=0.005, P=0.004, respectively). In
      multivariate analysis, the duration of persistent AF was the only predictor of
      freedom from AF (sinus rhythm or atrial tachycardia) (odds ratio, 0.80 for a 1
      year increase; 95% confidence interval, 0.67 to 0.95; P=0.01). Of 31 patients in
      whom AF recurred during follow-up, electrogram-based ablation was performed in
      the right atrium in 26 patients. Sixteen of those patients (62%) remained free
      from AF during follow-up. Overall, 82% of patients were free from any
      tachyarrhythmias at 2-year follow-up after a median of 2 procedures. CONCLUSIONS:
      Patients with shorter duration of persistent AF were more likely to be free from
      AF by LA ablation. Right atrial ablation may provide incremental efficacy in
      patients who are refractory to LA ablation.

PMID- 20693577
TI  - ATP-citrate lyase reduction mediates palmitate-induced apoptosis in pancreatic
      beta cells.
AB  - Elevated extracellular lipids, such as the free fatty acid palmitate, can induce
      pancreatic beta cell endoplasmic reticulum (ER) stress and apoptosis, thereby
      contributing to the initiation and progression of type 2 diabetes. ATP-citrate
      lyase (ACLY), a key enzyme in cellular lipid production, was identified as a
      palmitate target in a proteomic screen. We investigated the effects of palmitate
      on ACLY activity and phosphorylation and its role in beta cell ER stress and
      apoptosis. We demonstrated that treatment of MIN6 cells, mouse islets and human
      islets with palmitate reduced ACLY protein levels. These in vitro results were
      validated by our finding that islets from high fat-fed mice had a significant
      decrease in ACLY, similar to that previously observed in type 2 diabetic human
      islets. Palmitate decreased intracellular acetyl-CoA levels to a similar degree
      as the ACLY inhibitor, SB-204990, suggesting a reduction in ACLY activity. ACLY
      inhibitors alone were sufficient to induce CCAAT/enhancer-binding protein
      homologues protein (CHOP)-dependent ER stress and caspase-3-dependent apoptosis.
      Similarly, even modest shRNA-mediated knockdown of ACLY caused a significant
      increase in beta cell apoptosis and ER stress. The effects of chemical ACLY
      inhibition and palmitate were non-additive and therefore potentially mediated by
      a common mechanism. Indeed, overexpression of ACLY prevented palmitate-induced
      beta cell death. These observations provide new evidence that ACLY expression and
      activity can be suppressed by exogenous lipids and demonstrate a critical role
      for ACLY in pancreatic beta cell survival. These findings add to the emerging
      body of evidence linking beta cell metabolism with programmed cell death.

PMID- 20693578
TI  - Atrial tachyarrhythmias and repolarization changes induced by discrete activation
      of dorsal mediastinal cardiac nerves in canines.
AB  - BACKGROUND: Chronotropic "vagal responses" elicited by high-frequency stimulation
      have been used to identify atrial targets for ablative treatment of atrial
      tachyarrhythmias (AT), whereas an anatomic approach consisting of extensive
      ablation of the ganglionated plexus areas has been proposed as an alternative.
      Therefore, there is a need for precise delineation of juxtacardiac nerves
      involved in AT initiation and clarification of their regional influences
      throughout the atria in relation to AT sites of origin, beyond chronotropic
      effects related to sinus node modulation. METHODS AND RESULTS: Unipolar
      electrograms were recorded from 191 biatrial epicardial sites in 13 anesthetized
      canines, with concomitant left atrial endocardial recording from 63 sites in 5 of
      13 animals. When electric stimuli were delivered to dorsal mediastinal nerves
      during the atrial refractory period, atrial premature depolarizations initiating
      AT were elicited in all animals, most frequently without prior sinus cycle length
      modification. Among 63 episodes, the sites of origin of early AT beats were
      localized to (1) the posterolateral left atrial wall in the pulmonary vein region
      (33%), (2) superior left atrial loci along the Bachmann bundle (55%), and (3) the
      region of Bachmann bundle insertion into the superior right atrial wall (11%).
      Moreover, the AT sites of origin were spatially concordant with regional waveform
      changes during the repolarization phase of unipolar recordings. AT induction and
      repolarization changes were abolished after atropine administration. CONCLUSIONS:
      Activation of individual dorsal mediastinal nerves induces AT arising from
      distinct sites of origin which are spatially concordant with regional atrial
      repolarization changes.

PMID- 20693579
TI  - Ultraviolet A regulates adipogenic differentiation of human adipose tissue
      derived mesenchymal stem cells via up-regulation of Kruppel-like factor 2.
AB  - Adipocyte dysfunction is strongly associated with the development of obesity,
      which is a major risk factor for many disorders, including diabetes,
      hypertension, and heart disease. This study shows that ultraviolet A (UVA)
      inhibits adipogenic differentiation of human adipose tissue-derived mesenchymal
      stem cells and its action mechanisms. The mRNA levels of peroxidase proliferator
      activated receptor (PPAR) gamma and CCAAT/enhancer-binding protein alpha
      (C/EBPalpha), but not CCAAT/enhancer-binding protein ((C/EBP) beta and delta,
      were reduced by UVA. Moreover, the mRNA levels of PPAR gamma target genes
      (lipoprotein lipase (LPL), CD36, adipocyte protein (aP2), and liver X receptor
      alpha (LXR)) were down-regulated by UVA. Additionally, attempts to elucidate a
      possible mechanism underlying the UVA-mediated effects revealed that UVA induced
      migration inhibitory factor (MIF) gene expression, and this was mediated through
      activation of AP-1 (especially JNK and p42/44 MAPK) and nuclear factor-kappaB. In
      addition, reduced adipogenesis by UVA was recovered upon the treatment with anti
      MIF antibodies. AMP-activated protein kinase phosphorylation and up-regulation of
      Kruppel-like factor 2 (KLF2) were induced by UVA. Taken together, these findings
      suggest that the inhibition of adipogenic differentiation of human adipose tissue
      derived mesenchymal stem cells by UVA occurs primarily through the reduced
      expression of PPAR gamma, which is mediated by up-regulation of KLF2 via the
      activation of MIF-AMP-activated protein kinase signaling.

PMID- 20693580
TI  - Diastrophic dysplasia in a seven-year-old girl. Case study.
AB  - Diastrophic dysplasia is a rare genetic disorder characterised by short limbs and
      deformities of several joints occurring in conjunction with abnormal spinal
      curvatures, impaired metacarpal modelling and so-called hitchhiker thumbs. The
      condition is progressive and leads to considerable physical disability. It
      continues to constitute a challenge for doctors as the outcomes of corrective
      orthopaedic surgery are limited. The aim of this paper is to present the course
      of diastrophic dysplasia in a 7-year-old girl who also experienced cervical spine
      luxation with signs of compression of the spinal cord and carotid arteries. We
      describe deformities of the motor organs present in the patient and
      characteristic of diastrophic dysplasia, and the findings of specialised
      accessory investigations. The example of evaluation for bone disorders is used to
      draw attention to the principles of interpretation of densitometry measurements
      in a patient with impaired somatic development.

PMID- 20693581
TI  - Introducing pentavalent vaccine in the EPI in India: a counsel for caution.

PMID- 20693582
TI  - Tuberculosis control must be scientifically defined & soundly designed.

PMID- 20693583
TI  - PCR for diagnosis of malaria.

PMID- 20693584
TI  - Myth buster: caffeine does not exhibit a diuretic effect during exercise
      performance.

PMID- 20693585
TI  - Orthopaedic applications of bone graft & graft substitutes: a review.
AB  - Treatment of delayed union, malunion, and nonunion is a challenge to the
      orthopaedic surgeons in veterinary and human fields. Apart from restoration of
      alignment and stable fixation, in many cases adjunctive measures such as bone
      grafting or use of bone-graft substitutes are of paramount importance. Bone-graft
      materials usually have one or more components: an osteoconductive matrix, which
      acts as scaffold to new bone growth; osteoinductive proteins, which support
      mitogenesis of undifferentiated cells; and osteogenic cells, which are capable of
      forming bone in the appropriate environment. Autologous bone remains the "gold
      standard" for stimulating bone repair and regeneration, but its availability may
      be limited and the procedure to harvest the material is associated with
      complications. Bone-graft substitutes can either substitute autologous bone graft
      or expand an existing amount of autologous bone graft. We review the currently
      available bone graft and graft substitutes for the novel therapeutic approaches
      in clinical setting of orthopaedic surgery.

PMID- 20693586
TI  - Detection of mixed Plasmodium falciparum & P. vivax infections by nested-PCR in
      Pakistan, Iran & Afghanistan.
AB  - BACKGROUND & OBJECTIVES: Species identification and information on transmission
      pattern of malaria parasite in any malaria endemic area is key to success for a
      malaria control programme. In this investigation, malaria diagnosis using
      molecular method was used to assess the transmission pattern of malaria parasite
      in three malaria endemic regions: Afghanistan, Iran and Pakistan. METHODS: Blood
      samples were collected from the patients presenting with vivax malaria from
      Afghanistan (n=108), Iran (n=200) and Pakistan (n=199). Malaria parasite
      detection was made by the gold standard (microscopy) and also nested-PCR assay,
      using 18S small sub-unit ribosomal RNA (ssrRNA) gene. RESULTS: Based on
      microscopy method, the level of mixed infection was zero to 2.5 per cent;
      however, nested-PCR assay detected 6.5, 22 and 23.5 per cent mixed infections in
      samples collected from Afghanistan, Iran and Pakistan, respectively. The present
      results showed that the co-infection of P. vivax with P. falciparum was frequent
      in malaria endemic regions of Iran and Pakistan. INTERPRETATION & CONCLUSION: The
      present data suggest the need for improving microscopy diagnosis method and the
      clinician should also have careful clinical observation, along with the reports
      on Giemsa- stained thick blood films, particularly in summer time when P. vivax
      is predominant. Also sharing information on transmission pattern of mixed
      infection among these countries may help in designing better control strategies
      for malaria.

PMID- 20693587
TI  - Effects of acute supplementation of caffeine on cardiorespiratory responses
      during endurance running in a hot & humid climate.
AB  - BACKGROUND & OBJECTIVES: Athletes in Malaysia need to perform in a hot and humid
      climate. Chronic supplementation of caffeine on endurance performance have been
      studied extensively in different populations. However, concurrent research on the
      effects of acute supplementation of caffeine on cardiorespiratory responses
      during endurance exercise in the Malaysian context especially in a hot and humid
      environment is unavailable. METHODS: Nine heat adapted recreational Malaysian
      male runners (aged: 25.4+/-6.9 yr) who were nonusers of caffeine (23.7+/-12.6 mg
      per day) were recruited in this placebo--controlled double--blind randomized
      study. Caffeine (5 mg per kg of body weight) or placebo was ingested in the form
      of a capsule one hour prior to the running exercise trial at 70 per cent of
      VO2max on a motorised treadmill in a heat-controlled laboratory (31 degrees C,
      70% relative humidity). Subjects drank 3 ml of cool water per kg of body weight
      every 20 min during the running trials to avoid the adverse effects of
      dehydration. Heart rate, core body temperature and rate of perceived exertion
      (RPE) were recorded at intervals of 10 min, while oxygen consumption was measured
      at intervals of 20 min. RESULTS: Running time to exhaustion was significantly
      (P<0.05) higher in the caffeine trial compared to the placebo trial. Heart rate,
      core body temperature, oxygen uptake and RPE did not show any significant
      variation between the trials but it increased significantly during exercise from
      their respective resting values in both trials (P<0.001). INTERPRETATION &
      CONCLUSION: Our study showed that ingestion of 5 mg of caffeine per kg of body
      weight improved the endurance running performance but did not impose any
      significant effect on other individual cardiorespiratory parameters of heat
      acclimated recreational runners in hot and humid conditions.

PMID- 20693588
TI  - Anti-albuminuric efficacy of a combination of angiotensin converting enzyme
      inhibitor & angiotensin receptor blocker in type 1 DM with nephropathy.
AB  - BACKGROUND & OBJECTIVES: The efficacy of the combination of angiotensin receptor
      blockers (ARBs) and angiotensin converting enzyme (ACE) inhibitors in patients of
      type 1 diabetes mellitus (DM) with nephropathy is debatable. The antialbuminuric
      efficacy of dual blockade in patients of type 1 DM with micro- or macroabuminuria
      were evaluated. METHODS: In this open label observational study 30 patients (20
      male 10 female) with type 1 DM were included who were initially treated with
      telmisartan 80 mg for eight weeks followed by addition of ramipril 10 mg for a
      further eight weeks. Albuminuria reduction was studied at the end of each phase.
      RESULTS: Therapy with telmisartan for 8 wk resulted in a 39 per cent (P<0.01)
      reduction in albumin excretion rate (AER). Combination therapy with telmisartan
      and ramipril produced a further reduction in AER of 33.4 per cent (P<0.01),
      amounting to a total AER reduction of 59 per cent (P<0.001). Dual blockade was
      more effective in the group of macroalbuminuric as compared to microalbuminuric
      subjects (P<0.05). Telmisartan produced a significant reduction in SBP (P<0.05).
      The addition of ramipril produced a further reduction in BP, the total reduction
      being 10.3 in SBP and 7.2 mmHg in DBP (P<0.001 for both). There was an increase
      in mean serum potassium of 0.39 mmol/l (P<0.01) from baseline at the end of the
      study period and two patients had hyperkalemia>5.5 mmol/l with dual blockade.
      INTERPRETATION & CONCLUSION: Dual blockade with ramipril enhanced the
      antialbuminuric efficacy of telmisartan and further reduced blood pressure. The
      effect of dual blockade was more pronounced in the macroalbuminuric subjects and
      it was well tolerated. However, careful monitoring of serum potassium is
      required.

PMID- 20693589
TI  - Inheritance patterns, consanguinity & risk for asthma.
AB  - BACKGROUND & OBJECTIVES: Family history is an important risk factor for the
      development of asthma, contingent upon genetic and environment interaction. Since
      there is paucity of data on asthma inheritance in Indian population, the present
      study was undertaken to investigate the inheritance patterns of asthma and the
      effect of family history and consanguineous marriage on asthma inheritance.
      METHODS: A total of 200 families, 100 index children and 100 index adults with
      clinically diagnosed asthma, along with 400 non-asthmatic children and adults as
      controls were selected for the present study. Information about the family
      history of each patients and controls was collected and analyzed pedigrees were
      also constructed. RESULTS: A history of asthma in any member of the family was
      observed in 44.5 per cent of cases and 5.3 per cent of controls (P<0.001). A
      differential risk of developing asthma was noted in family history of asthma in
      different first and second degree relatives of children and adult patients.
      Consanguineous marriage was also noted in parents in 24.5 per cent of cases and
      12.3 per cent of controls (P<0.001). The most common mode of asthma inheritance
      was recessive. INTERPRETATION & CONCLUSIONS: Our results showed that
      consanguineous marriage and family history of asthma are important determinants
      in the development of asthma in the offspring.

PMID- 20693590
TI  - Role of GGT in diagnosis of metabolic syndrome: a clinic-based cross-sectional
      survey.
AB  - BACKGROUND & OBJECTIVES: The aim of this study is to know if the liver function
      tests (LFT), especially gamma glutamyl transferase (GGT), have a predictive value
      in diagnosis of metabolic syndrome (MS). METHODS: A cross-sectional, single
      center study was carried out with 908 subjects. Four hundred and forty two of
      these subjects were diagnosed with MS with IDF criteria; while other 466 were sex
      and age matched healthy control subjects. Blood pressure, liver function tests,
      fasting blood glucose levels and lipid profile of the subjects were recorded.
      RESULTS: The mean values of alanine amino transferase (ALT), aspartate
      aminotransferase (AST) and GGT levels were statistically significantly higher in
      MS group. The mean values of liver enzymes, for female/ male subjects in MS
      group, AST; ALT and GGT respectively, were; 20.5/19.7 U/l; 25.9/28.5 U/l;
      35.9/42.1 U/l. When the sample is divided into quartiles of the GGT levels,
      increase in GGT is positively correlated with increased MS prevalence. In ROC
      analysis GGT is as strongly associated with the IDF diagnostic components as is
      each individual IDF component, except elevated systolic blood pressure. In
      covariance analysis, there was significant relationship between elevated GGT
      levels and MS presence after adjustment for age, sex and MS diagnostic criteria;
      but not AST and ALT levels. In multivariance analysis, in MS group, a high GGT
      was positively associated with CVD prevalance (odds ratio: 2.011, 95% CI 1.10
      4.57) compared to low GGT group independent of age, sex and smoking habits.
      INTERPRETATION & CONCLUSIONS: Elevated liver enzymes, although in normal ranges,
      especially at upper quartiles, play a central role in early diagnosis of fat
      overflow to the liver. Regarding the availability and simplicity of these tests
      in routine clinical practice, they, especially GGT, have potential to be
      considered in algorithms for metabolic syndrome.

PMID- 20693591
TI  - Polymorphic variants of beta1 adrenergic receptor gene (Ser49Gly & Arg389Gly) in
      healthy Tamilian volunteers.
AB  - BACKGROUND & OBJECTIVES: Several studies reported the polymorphisms of beta1
      adrenergic receptor gene in healthy volunteers and its influence on
      cardiovascular disorders. We investigated the genotype and allele frequencies of
      Ser49Gly and Arg389Gly polymorphism in healthy volunteers of South Indian
      Tamilian population vis-a-vis other major ethnic groups. METHODS: The genetic
      variants were determined by using Taqman 5' nuclease assay- real time PCR
      analysis in 533 normal healthy volunteers (18-60 yr; M=290; F=243). The allelic
      discrimination analysis was done by 7700 SDS software. RESULTS: The estimated
      genotype and allele frequencies of Ser49Gly and Arg389Gly polymorphism were
      compared with other major populations. The frequencies of the variant alleles
      Gly49 and Gly389 were 15.1 and 25.8 per cent respectively. INTERPRETATION &
      CONCLUSIONS: Our study shows that interethnic variation exists in the
      polymorphisms of beta1-adrenergic receptor gene and the results generated in this
      study might serve as a genetic marker for further studies in Tamilian (South
      India) population.

PMID- 20693592
TI  - Pandemic influenza A(H1N1) 2009 outbreak in a residential school at Panchgani,
      Maharashtra, India.
AB  - BACKGROUND & OBJECTIVES: An outbreak of influenza was investigated between June
      24 and July 30, 2009 in a residential school at Panchgani, Maharashtra, India.
      The objectives were to determine the aetiology, study the clinical features in
      the affected individuals and, important epidemiological and environmental
      factors. The nature of public health response and effectiveness of the control
      measures were also evaluated. METHODS: Real time reverse transcriptase polymerase
      chain reaction was performed on throat swabs collected from 82 suspected cases to
      determine the influenza types (A or B) and sub-types [pandemic (H1N1) 2009, as
      well as seasonal influenza H1N1, H3N2]. Haemagglutination inhibition assay was
      performed on serum samples collected from entire school population (N=415) to
      detect antibodies for pandemic (H1N1) 2009, seasonal H1N1, H3N2 and influenza
      B/Yamagata and B/Victoria lineages. Antibody titres>or=10 for pandemic (H1N1)
      2009 and >or=20 for seasonal influenza A and B were considered as positive for
      these viruses. RESULTS: Clinical attack rate for influenza-like illness was 71.1
      per cent (295/415). The attack rate for pandemic (H1N1) 2009 cases was 42.4 per
      cent (176/415). Throat swabs were collected from 82 cases, of which pandemic
      (H1N1) 2009 virus was detected in 15 (18.3%), influenza type A in (6) 7.4 per
      cent and influenza type B only in one case. A serosurvey carried out showed
      haemagglutination inhibition antibodies to pandemic (H1N1) 2009 in 52 per cent
      (216) subjects in the school and 9 per cent (22) in the community. INTERPRETATION
      & CONCLUSION: Our findings confirmed an outbreak of pandemic (H1N1) 2009 due to
      local transmission among students in a residential school at Panchgani,
      Maharashtra, India.

PMID- 20693593
TI  - Comparison of MGIT 960 & pyrazinamidase activity assay for pyrazinamide
      susceptibility testing of Mycobacterium tuberculosis.
AB  - BACKGROUND & OBJECTIVES: Pyrazinamide is an important front line
      antimycobacterial drug, which is also being used in the treatment of multi drug
      resistant tuberculosis along with second line drugs in DOTS plus programme.
      Conventional testing of pyrazinamide on solid medium is difficult as it is active
      at acidic pH. Therefore, there is a need for a rapid and simple method for
      susceptibility testing of pyrazinamide. This study was carried out to compare
      pyrazinamide susceptibility testing by MGIT 960 and two rapid pyrazinamidase
      activity tests. METHODS: Pyrazinamide susceptibility was tested in 136 clinical
      isolates of Mycobacterium tuberculosis by MGIT 960 and pyrazinamidase activity
      was tested by classical Wayne's method and modified PZase agar method. RESULTS:
      There was 88.9 per cent concordance between MGIT 960 and classical Wayne's method
      and 93.38 per cent with modified method for pyrazinamidase activity. Using MGIT
      960 results as gold standard the sensitivity and specificity of Wayne's method
      was 88.15 and 90 per cent respectively and that of modified method was 89.4 and
      98.3 per cent. INTERPRETATION & CONCLUSIONS: Our study demonstrates that the
      modified pyrazinamidase activity test can be used as a screening test to detect
      resistance to pyrazinamide specially in resource limited settings but
      confirmation of susceptibility should be done by standard methods like MGIT 960.

PMID- 20693594
TI  - Ultrasonography for diagnosis of abdominal tuberculosis in HIV infected people.
AB  - BACKGROUND & OBJECTIVES: There is an increasing incidence of abdominal
      tuberculosis with the advent of HIV infection. This study was aimed at
      determining the pattern of presentation of abdominal tuberculosis on
      ultrasonography (USG) in HIV positive patients. METHODS: This retrospective study
      was carried at the ART Centre, Sir Sunderlal Hospital, Banaras Hindu University,
      Varanasi, between March 2005 to July 2007. HIV positive patients (n=2453) with
      prolonged fever, abdominal pain/distension, altered bowel habits and diarrhoea
      underwent ultrasonography for tuberculosis of abdomen. The different
      ultrasonological findings in abdominal tuberculosis were noted. CD4 counts of
      these patients were also recorded. RESULTS: Of the total 2453 patients, 244
      showed findings suggestive of abdominal tuberculosis. Lymphadenopathy with
      predominantly hypoechoic/necrotic echotexture was seen in 158/244 (64.8%)
      patients. Splenomegaly was seen in 68 patients with 61 of them (89.7%) showing
      multiple hypoechoic lesions in the parenchyma. 53 of 244 (21.7%) showed extensive
      abdominal involvement. Liver enlargement was seen as a part of extensive
      abdominal involvement. A total of 203 patients completed antitubercular
      treatment, of which 198 (97.5%) showed resolution of lesions in USG. CD4 counts
      in patients with extensive abdominal involvement were lowest compared to CD4
      count in patients with others USG findings. INTERPRETATION & CONCLUSION:
      Ultrasonological findings like lymphadenopathy (>or=1.5 cm) with
      hypoechoeic/necrotic echotexture, hypoechoic splenic lesions and extensive
      abdominal involvement in HIV infected patients may be suggestive of abdominal
      tuberculosis.

PMID- 20693595
TI  - Evaluation of risk factors for antituberculosis treatment induced hepatotoxicity.
AB  - BACKGROUND & OBJECTIVES: Antituberculosis (anti-TB) drug induced hepatotoxicity
      (DIH) is the most common side effect leading to interruption of therapy. Wide
      variations have been found in the reported incidence of hepatotoxicity during
      short-course chemotherapy. Several risk factors for hepatotoxicity have been
      suggested in previous studies. We undertook a prospective case-control study to
      assess the role of these putative risk factors in the development of DIH in
      patients receiving anti-TB treatment. METHODS: One hundred and seventy five
      consecutive cases with a diagnosis of anti-TB DIH were compared with 428
      consecutive controls who took anti-TB drugs for the full duration of chemotherapy
      without clinical or biochemical evidence of hepatitis. Cases positive for markers
      of acute viral hepatitis were carefully excluded. Cases and controls were
      compared with respect to age, sex, site of tuberculosis, radiological extent of
      disease on chest radiograph, body mass index (BMI), mid-arm circumference (MAC)
      and liver function at baseline which included serum bilirubin, aspartate
      aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase
      (ALP), serum total protein and serum albumin. RESULTS: Univariate logistic
      regression revealed that the risk of developing DIH was greater in older
      patients. Significantly greater percentage of cases had extrapulmonary
      tuberculosis (TB) (P<0.01). Also, a significantly higher percentage of cases had
      moderate to far advanced disease severity on chest radiograph (P<0.01). On
      multivariate logistic regression, the adjusted odds were significant (P<0.01) for
      age>35 yr, MAC<20 cm and hypoalbuminaemia (albumin<3.5 g/dl). INTERPRETATION &
      CONCLUSIONS: Older age, poor nutritional status including baseline
      hypoalbuminaemia were independent predictors of occurrence of anti-TB DIH.
      Clinicians should be vigilant for occurrence of hepatotoxicity in this high risk
      group.

PMID- 20693596
TI  - Effect of ozone on response to ovalbumin & its modulation by vitamins C & E in
      sensitized guinea pigs.
AB  - BACKGROUND & OBJECTIVES: Exposure to ozone and asthma are both associated with
      increased oxidative stress. Exposure to ozone therefore, may potentiate the
      airway response to allergens. We undertook this study to investigate the effect
      of ozone exposure on airway response to ovalbumin in sensitized guinea pigs and
      its modulation by dietary supplementation with antioxidant vitamins C and E.
      METHODS: After in vivo measurements of specific airways conductance (SGaw) and
      airway hyperresponsiveness (AHR) to inhaled histamine, guinea pigs were
      sensitized to ovalbumin and divided into three groups: (i) sensitized; (ii)
      sensitized and exposed daily to ozone; and (iii) sensitized, exposed daily to
      ozone and given dietary supplementation with vitamin C, 2 mg/kg body wt and E, 7
      IU/kg body wt. A control group of nonsensitized animals was included. After 4 wk,
      AHR was measured again and animals were challenged with inhaled ovalbumin.
      Changes in SGaw were followed for early and late airway bronchoconstrictive
      responses. The following measurements were obtained: (i) parameters of oxidative
      stress--plasma malonaldehyde (MDA) as marker of lipid peroxidation and superoxide
      anion generation by leukocytes and bronchoalveolar lavage (BAL) cells; (ii)
      antioxidant status: red cell superoxide dismutase (SOD); and (iii) glutathione
      peroxidase (GPx). BAL cytology was studied. RESULTS: Ozone exposure resulted in
      an increase in AHR and early and late bronchoconstrictive responses after
      ovalbumin challenge, greater superoxide anion generation in BAL cells, higher
      plasma MDA levels and decrease in red cell SOD activity. Dietary supplementation
      with vitamin C and E prevented or ameliorated these responses. INTERPRETATION &
      CONCLUSIONS: Exposure to ozone at concentrations of 0.12 ppm for 2 h daily for 4
      wk enhances the airway response to allergens in sensitized guinea pigs. Dietary
      supplementation with antioxidant vitamins E and C, affords variable degree of
      protection against this enhancement.

PMID- 20693597
TI  - Antibacterial & antiplasmid activities of Helicteres isora L.
AB  - BACKGROUND & OBJECTIVES: The multiple drug resistance (MDR) is a serious health
      problem and major challenge to the global drug discovery programmes. Most of the
      genetic determinants that confer resistance to antibiotics are located on R
      plasmids in bacteria. The present investigation was undertaken to investigate the
      ability of organic extract of the fruits of Helicteres isora to cure R-plasmids
      from certain clinical isolates. METHODS: Active fractions demonstrating
      antibacterial and antiplasmid activities were isolated from the acetone extracts
      of shade dried fruits of H. isora by bioassay guided fractionation. Minimal
      inhibitory concentration (MIC) of antibiotics and organic extracts was determined
      by agar dilution method. Plasmid curing activity of organic fractions was
      determined by evaluating the ability of bacterial colonies (pre treated with
      organic fraction for 18 h) to grow in the presence of antibiotics. The physical
      loss of plasmid DNA in the cured derivatives was further confirmed by agarose gel
      electrophoresis. RESULTS: The active fraction did not inhibit the growth of
      either the clinical isolates or the strains harbouring reference plasmids even at
      a concentration of 400 microg/ml. However, the same fraction could cure plasmids
      from Enterococcus faecalis, Escherichia coli, Bacillus cereus and E. coli (RP4)
      at curing efficiencies of 14, 26, 22 and 2 per cent respectively. The active
      fraction mediated plasmid curing resulted in the subsequent loss of antibiotic
      resistance encoded in the plasmids as revealed by antibiotic resistance profile
      of cured strains. The physical loss of plasmid was also confirmed by agarose gel
      electrophoresis. INTERPRETATION & CONCLUSIONS: The active fraction of acetone
      extract of H. isora fruits cured R-plasmids from Gram-positive and Gram-negative
      clinical isolates as well as reference strains. Such plasmid loss reversed the
      multiple antibiotic resistance in cured derivatives making them sensitive to low
      concentrations of antibiotics. Acetone fractions of H. isora may be a source to
      develop antiplasmid agents of natural origin to contain the development and
      spread of plasmid borne multiple antibiotic resistance.

PMID- 20693598
TI  - Evaluation of COBAS TaqMan real time PCR assay for the diagnosis of Mycobacterium
      tuberculosis.

PMID- 20693599
TI  - Lesson from surveillance of drug-resistant tuberculosis in Gujarat.

PMID- 20693600
TI  - An outbreak of dengue fever in Tirupur, Coimbatore district, Tamil Nadu.

PMID- 20693601
TI  - The current swine flu pandemic may provide some opportunity for future research
      of schizophrenia.

PMID- 20693602
TI  - ROME scheme: from reorientation to research oriented medical education, a new
      beginning.

PMID- 20693603
TI  - Research oriented medical education.

PMID- 20693604
TI  - miReg: a resource for microRNA regulation.
AB  - MicroRNAs (miRNAs/miRs) are important cellular components that regulate gene
      expression at posttranscriptional level. Various upstream components regulate miR
      expression and any deregulation causes disease conditions. Therefore,
      understanding of miR regulatory network both at upstream and downstream level is
      crucial and a resource on this aspect will be helpful. Currently available miR
      databases are mostly related to downstream targets, sequences, or diseases. But
      as of now, no database is available that provides a complete picture of miR
      regulation in a specific condition. Our miR regulation web resource (miReg) is a
      manually curated one that represents validated upstream regulators (transcription
      factor, drug, physical, and chemical) along with downstream targets, associated
      biological process, experimental condition or disease state, up or down
      regulation of the miR in that condition, and corresponding PubMed references in a
      graphical and user friendly manner, browseable through 5 browsing options. We
      have presented exact facts that have been described in the corresponding
      literature in relation to a given miR, whether it's a feed-back/feed-forward loop
      or inhibition/activation. Moreover we have given various links to integrate data
      and to get a complete picture on any miR listed. Current version (Version 1.0) of
      miReg contains 47 important human miRs with 295 relations using 190 absolute
      references. We have also provided an example on usefulness of miReg to establish
      signalling pathways involved in cardiomyopathy. We believe that miReg will be an
      essential miRNA knowledge base to research community, with its continuous upgrade
      and data enrichment. This HTML based miReg can be accessed from: www.iioab
      mireg.webs.com or www.iioab.webs.com/mireg.htm.

PMID- 20693606
TI  - A novel integrative phylogenetic analysis system.
AB  - Existing phylogenetic methods cannot realistically model the evolutionary
      process. It has become a serious issue for real-life applications which demand
      accurate phylogenetic results. It is desirable to have an integrative approach
      which can effectively incorporate multi-disciplinary analyses and synthesise
      results from various sources. A novel integrative and interactive computing
      system has been developed to address such an issue. We introduce the concept of
      super-quartet and explain how it is adopted for effective integration of other
      computational methods to the algorithm during computation &ndash; a key issue of
      the development of integrative and interactive computing system.

PMID- 20693605
TI  - Xenohormetic, hormetic and cytostatic selective forces driving longevity at the
      ecosystemic level.
AB  - We recently found that lithocholic acid (LCA), a bile acid, extends yeast
      longevity. Unlike mammals, yeast do not synthesize bile acids. We therefore
      propose that bile acids released into the environment by mammals may act as
      interspecies chemical signals providing longevity benefits to yeast and, perhaps,
      other species within an ecosystem.

PMID- 20693607
TI  - Improving CT prediction of treatment response in patients with metastatic
      colorectal carcinoma using statistical learning.
AB  - To establish radiologic imaging as a valid biomarker for assessing the response
      of cancer to different treatments. We study patients with metastatic colorectal
      carcinoma to learn whether Statistical Learning Theory (SLT) improves the
      performance of radiologists using Computer Tomography (CT) in predicting patient
      treatment response to therapy compared with traditional Response Evaluation
      Criteria in Solid Tumours (RECIST) standard. Preliminary research demonstrated
      that SLT algorithms can address questions and criticisms associated with both
      RECIST and World Health Organization (WHO) scoring methods. We add tumour
      heterogeneity, shape, etc., obtained from CT or MRI scans the feature vector for
      processing.

PMID- 20693608
TI  - Predicting protein complexes by data integration of different types of
      interactions.
AB  - The explosion of high throughput interaction data from proteomics studies gives
      us the opportunity to integrate Protein-Protein Interactions (PPI) from different
      type of interactions. These methods rely on the assumption that proteins within a
      complex have more interactions across the different data sets which translate
      into the identification of dense subgraphs. However, the relative importance of
      the types of interaction are not equivalent in their reliability and accuracy
      consequently they should be analysed separately. Here we propose a method that
      use graph theory and mathematical modelling to solve this problem. Our approach
      has four steps that: i) score independently each type of interaction; ii) build
      an interaction specific networks for each type; iii) weight the specific
      networks; and iv) combine and normalise the scores. Using this approach to the
      BRCA1 Associated genome Surveillance Complex (BASC), we correctly identified the
      known core components of the complex and subcomplexes that have solved structures
      as well as predicted new interactions and core complexes. The method presented in
      this study is of general use. It is flexible enough to allow the development of
      any scoring system and can be applied to any protein complex to provide the
      latest knowledge in its interactions and structure.

PMID- 20693609
TI  - Multi-level integrative analysis of Protein Protein Interaction networks:
      connecting completeness, depth and robustness.
AB  - A fully extended Protein Protein Interaction (PPI) network can consist of upwards
      of several thousand nodes and edges. To simplify analysis, smaller child samples
      are often used in substitution of the global network. In this study, the impact
      of different levels of sampling was evaluated on six PPI networks. Results from
      the case studies suggest that restricting analysis to the first network level,
      using metrics such as degree and BC, could lead to misrepresentative results,
      omitting potentially significant nodes. Fault-tolerance analysis also indicates
      that key nodes within the second network level, and above, contribute to the
      stability of the global network.

PMID- 20693611
TI  - Sequence alignment and phylogenetic analysis of Human Herpes Simplex Virus (HHV)
      using bioinformatics tool: a review.
AB  - Bioinformatics is the application of computational techniques to analyse the wet
      lab information associated with biomolecules on a commercial scale. Today's it
      concentrate on structural biology, genomics to gene expression studies. In this
      review we discuss the main principles that desirable bioinformatics analyses,
      sequence alignment and phylogenetic analysis from biological databases that are
      commonly used and examine some of the studies that are being conducted,
      particularly with reference to Human Herpes Simplex Virus (HHV). Finally provide
      an introduction and overview of the bioinformatics tools and software used for
      sequence alignment.

PMID- 20693610
TI  - Identifying genes progressively silenced in preneoplastic and neoplastic liver
      tissues.
AB  - High-throughput genomic technologies are increasingly being used to identify
      therapeutic targets and risk factors for specific diseases. Using 116 independent
      liver samples, we identified 793 probe sets that demonstrated a significant
      association in the frequency of absent calls as tissues progressed from normal to
      pre-neoplastic to neoplastic, followed by a bioinformatic approach which
      identified that 78.9% of the significant probe sets contained at least one CpG
      island in the gene promoter region compared with 58.9% of the remaining genes
      examined. Our results indicate that further high-throughput methylation studies
      to more fully characterize molecular events involved in hepatocarcinogenesis are
      warranted.

PMID- 20693613
TI  - Determination of average LET of therapeutic proton beams using Al2O3:C optically
      stimulated luminescence (OSL) detectors.
AB  - In this work we present a methodology and proof of concept to experimentally
      determine average linear energy transfer (LET) of therapeutic proton beams using
      the optically stimulated luminescence (OSL) of small Al(2)O(3):C detectors. Our
      methodology is based on the fact that the shape of the OSL decay curve of
      Al(2)O(3):C detectors depends on the LET of the radiation field. Thus, one can
      use the shape of the OSL decay curves to establish an LET calibration curve,
      which in turn permits measurements of LET. We performed irradiations at the M D
      Anderson Cancer Center Proton Therapy Center, Houston (PTCH), with passive
      scattering beams. We determined the average LET of the passive scattering beams
      using a validated Monte Carlo model of the PTCH passive scattering nozzle and
      correlated them with the shape of the OSL decay curve to obtain an LET
      calibration curve. Using this calibration curve and OSL measurements, we
      determined the averaged LET at various water-equivalent depths for therapeutic
      spread-out Bragg peaks and compared the results with averaged LETs determined
      using the Monte Carlo simulations. Agreement between measured and simulated
      fluence-averaged LET was within 24% for low energy spread-out Bragg peak (SOBP)
      fields and within 14% for high energy SOBP fields. Agreement between measured and
      simulated dose-averaged LET was within 12% for low energy SOBP fields and within
      47% for high energy SOBP fields. The data presented in this work demonstrated the
      correlation between the OSL decay curve shapes and the average LET of the
      radiation fields, providing proof of concept of the feasibility of using OSL from
      Al(2)O(3):C detectors to measure average LET of therapeutic proton beams.

PMID- 20693612
TI  - A feasibility study using radiochromic films for fast neutron 2D passive
      dosimetry.
AB  - The objective of this paper is threefold: (1) to establish sensitivity of XRQA
      and EBT radiochromic films to fast neutron exposure; (2) to develop a film
      response to radiation dose calibration curve and (3) to investigate a two
      dimensional (2D) film dosimetry technique for use in establishing an experimental
      setup for a radiobiological irradiation of mice and to assess the dose to the
      mice in this setup. The films were exposed to a 10 MeV neutron beam via the
      (2)H(d,n)(3)He reaction. The XRQA film response was a factor of 1.39 greater than
      EBT film response to the 10 MeV neutron beam when exposed to a neutron dose of
      165 cGy. A film response-to-soft tissue dose calibration function was established
      over a range of 0-10 Gy and had a goodness of fit of 0.9926 with the calibration
      data. The 2D film dosimetry technique estimated the neutron dose to the mice by
      measuring the dose using a mouse phantom and by placing a piece of film on the
      exterior of the experimental mouse setup. The film results were benchmarked using
      Monte Carlo and aluminum (Al) foil activation measurements. The radiochromic
      film, Monte Carlo and Al foil dose measurements were strongly correlated, and the
      film within the mouse phantom agreed to better than 7% of the externally mounted
      films. These results demonstrated the potential application of radiochromic films
      for passive 2D neutron dosimetry.

PMID- 20693614
TI  - In vitro characterization of perfluorocarbon droplets for focused ultrasound
      therapy.
AB  - Focused ultrasound therapy can be enhanced with microbubbles by thermal and
      cavitation effects. However, localization of treatment is difficult as bioeffects
      can occur outside of the target region. Spatial control of bubbles can be
      achieved by ultrasound-induced conversion of liquid perfluorocarbon droplets to
      gas bubbles. This study was undertaken to determine the acoustic parameters for
      bubble production by droplet conversion and how it depends on the acoustic
      conditions and droplet physical parameters. Lipid-encapsulated droplets
      containing dodecafluoropentane were manufactured with sizes ranging from 1.9 to
      7.2 microm in diameter and diluted to a concentration of 8 x 10(6) droplets mL(
      1). The droplets were sonicated in vitro with a focused ultrasound transducer and
      varying frequency and exposure under flow conditions through an acoustically
      transparent vessel. The sonications were 10 ms in duration at frequencies of
      0.578, 1.736 and 2.855 MHz. The pressure threshold for droplet conversion was
      measured with an active transducer operating in pulse-echo mode and simultaneous
      measurements of broadband acoustic emissions were performed with passive acoustic
      detection. The results show that droplets cannot be converted at low frequency
      without broadband emissions occurring. However, the pressure threshold for
      droplet conversion decreased with increasing frequency, exposure and droplet
      size. The pressure threshold for broadband emissions was independent of the
      droplet size and was 2.9, 4.4 and 5.3 MPa for 0.578, 1736 and 2.855 MHz,
      respectively. In summary, we have demonstrated that droplet conversion is
      feasible for clinically relevant sized droplets and acoustic exposures.

PMID- 20693615
TI  - An investigation of the trade-off between the count level and image quality in
      myocardial perfusion SPECT using simulated images: the effects of statistical
      noise and object variability on defect detectability.
AB  - Quantum noise as well as anatomic and uptake variability in patient populations
      limits observer performance on a defect detection task in myocardial perfusion
      SPECT (MPS). The goal of this study was to investigate the relative importance of
      these two effects by varying acquisition time, which determines the count level,
      and assessing the change in performance on a myocardial perfusion (MP) defect
      detection task using both mathematical and human observers. We generated ten sets
      of projections of a simulated patient population with count levels ranging from
      1/128 to around 15 times a typical clinical count level to simulate different
      levels of quantum noise. For the simulated population we modeled variations in
      patient, heart and defect size, heart orientation and shape, defect location,
      organ uptake ratio, etc. The projection data were reconstructed using the OS-EM
      algorithm with no compensation or with attenuation, detector response and scatter
      compensation (ADS). The images were then post-filtered and reoriented to generate
      short-axis slices. A channelized Hotelling observer (CHO) was applied to the
      short-axis images, and the area under the receiver operating characteristics
      (ROC) curve (AUC) was computed. For each noise level and reconstruction method,
      we optimized the number of iterations and cutoff frequencies of the Butterworth
      filter to maximize the AUC. Using the images obtained with the optimal iteration
      and cutoff frequency and ADS compensation, we performed human observer studies
      for four count levels to validate the CHO results. Both CHO and human observer
      studies demonstrated that observer performance was dependent on the relative
      magnitude of the quantum noise and the patient variation. When the count level
      was high, the patient variation dominated, and the AUC increased very slowly with
      changes in the count level for the same level of anatomic variability. When the
      count level was low, however, quantum noise dominated, and changes in the count
      level resulted in large changes in the AUC. This behavior agreed with a
      theoretical expression for the AUC as a function of quantum and anatomical noise
      levels. The results of this study demonstrate the importance of the tradeoff
      between anatomical and quantum noise in determining observer performance. For
      myocardial perfusion imaging, it indicates that, at current clinical count
      levels, there is some room to reduce acquisition time or injected activity
      without substantially degrading performance on myocardial perfusion defect
      detection.

PMID- 20693616
TI  - Surface-enhanced localized surface plasmon resonance biosensing of avian
      influenza DNA hybridization using subwavelength metallic nanoarrays.
AB  - We demonstrated enhanced localized surface plasmon resonance (SPR) biosensing
      based on subwavelength gold nanoarrays built on a thin gold film. Arrays of
      nanogratings (1D) and nanoholes (2D) with a period of 200 nm were fabricated by
      electron-beam lithography and used for the detection of avian influenza DNA
      hybridization. Experimental results showed that both nanoarrays provided
      significant sensitivity improvement and, especially, 1D nanogratings exhibited
      higher SPR signal amplification compared with 2D nanohole arrays. The sensitivity
      enhancement is associated with changes in surface-limited reaction area and
      strong interactions between bound molecules and localized plasmon fields. Our
      approach is expected to improve both the sensitivity and sensing resolution and
      can be applicable to label-free detection of DNA without amplification by
      polymerase chain reaction.

PMID- 20693617
TI  - Adsorption of hematite nanoparticles onto Caco-2 cells and the cellular
      impairments: effect of particle size.
AB  - The increasing applications of engineered nanomaterials nowadays have elevated
      the potential of human exposure through various routes including inhalation, skin
      penetration and digestion. To date there is scarce information on a quantitative
      description of the interactions between nanoparticles (NPs) and cell surfaces and
      the detrimental effects from the exposure. The purpose of this work was to study
      in vitro exposure of Caco-2 cells to hematite (alpha-Fe(2)O(3)) NPs and to
      determine the particle size effects on the adsorption behaviors. Cellular
      impairment was also investigated and compared. Hematite NPs were synthesized as
      part of this study with a discrete size distribution and uniform morphology
      examined by dynamic light scattering (DLS) and confirmed by transmission electron
      microscopy (TEM). Caco-2 cells were cultured as a model epithelium to mirror
      human intestinal cells and used to evaluate the impacts of the exposure to NPs by
      measuring transepithelial electrical resistance (TEER). Cell surface disruption,
      localization and translocation of NPs through the cells were analyzed with
      immunocytochemical staining and confocal microscopy. Results showed that hematite
      NPs had mean diameters of 26, 53, 76 and 98 nm and were positively charged with
      minor aggregation in the buffer solution. Adsorption of the four sizes of NPs on
      cells reached equilibrium within approximately 5 min but adsorption kinetics were
      found to be size-dependent. The adsorption rates expressed as mg m(-2) min(-1)
      were greater for large NPs (76 and 98 nm) than those for small NPs (26 and 53
      nm). However, adsorption rates, expressed in units of m(-2) min(-1), were much
      greater for small NPs than large ones. After the adsorption equilibrium was
      reached, the adsorbed mass of NPs on a unit area of cells was calculated and
      showed no significant size dependence. Longer exposure time (>3 h) induced
      adverse cellular effects as indicated by the drop in TEER compared to the control
      cells without the exposure to NPs. NPs initially triggered a dynamic
      reorganization and detachment of microvilli structures on Caco-2 cell surfaces.
      Following this impact, the drop in TEER occurred more significantly, particularly
      for the exposure to 26 nm NPs, which was consistent with the observations with
      confocal microscopy that the junctions were more severely disrupted by 26 nm NPs
      than other sizes. In conclusion, this paper demonstrates the interactions at the
      ultrastructural level from initial surface adsorption of NPs upon cells, to the
      subsequent microvilli reorganization, membrane penetration and the disruption of
      adherens junction and provides the fundamental information on size effects on NP
      behavior which is often poorly addressed for in vitro cytotoxicity studies of
      NPs.

PMID- 20693618
TI  - Zinc oxide scaffolds on MgO nanocubes.
AB  - Powders of isolated and well-dispersed oxide nanocubes are promising components
      for photoelectronic applications that benefit from tunable optical properties,
      surface reactivity and the ease of realization of their controlled assembly.
      Here, we demonstrate that combustion of zinc and magnesium metal vapors at
      reduced pressures followed by subsequent vacuum annealing of the resulting
      nanoparticle powders yields single-crystalline Zn(x)Mg(1-x)O nanocubes of
      exceptional regular cubic shape and edge lengths below 25 nm. In line with ab
      initio calculations, which predict preferential Zn(2+) segregation into low
      coordinated surface elements of the MgO nanocubes, we track the occupation of
      edge sites by chains of Zn(2+)-O(2-) units through their spectroscopic
      signatures. As a method to generate composite nanostructures with controlled
      spatial distribution of the chemical components, the annealing induced ion
      segregation can be extended to other well-dispersed metastable nanoparticles. We
      expect that the energy of segregation mainly depends on the site coordination
      number, which can promote controlled demixing within the nanoparticles.

PMID- 20693619
TI  - Self-assembled structures of hydrogen-bonded poly(vinyl chloride-g-4-vinyl
      pyridine) graft copolymers.
AB  - An amphiphilic graft copolymer of poly(vinyl chloride-graft-4-vinyl pyridine),
      i.e., PVC-g-P4VP was synthesized via atom transfer radical polymerization (ATRP)
      and modified by introducing 1,5-dihydroxynaphthalene (DHN) as a hydrogen bonding
      donor to form hydrogen-bonded macromolecules. The PVC-g-P4VP graft copolymer
      prepared from a selective solvent for PVC, i.e., tetrahydrofuran (THF) exhibited
      a well-organized micellar morphology consisting of a P4VP core and a PVC corona.
      However, the graft copolymer prepared from a good solvent for both domains, i.e.,
      N, N-dimethylformamide (DMF) showed a less-organized, random microphase-separated
      morphology. Upon the introduction of DHN, a more spherical morphology and a more
      organized 'bicontinuous-like' morphology was observed in THF and DMF,
      respectively. This results from strong segregation between the two domains due to
      the enhanced interfacial energy by DHN. When DHN was removed by methanol,
      nanoporous films with versatile pore sizes and shapes were generated.

PMID- 20693620
TI  - Alzheimer Center Reina Sofia Foundation: fighting the disease and providing
      overall solutions.
AB  - As the impact of Alzheimer's disease (AD) on society expands, the reaction aimed
      at neutralizing its effects also increases. In Spain, an initiative arisen from
      the highest institution of the State has launched a crusade for fighting the
      disease from a multidisciplinary stance. In 2002, the "Alzheimer Project" of the
      Reina Sofia Foundation was announced and in 2007, the Alzheimer Center Reina
      Sofia Foundation was inaugurated. This resource includes a long-term inpatient
      care facility, a day-care center, premises for education and training, and a
      research unit. This way, patients and investigators share the space in a clear
      expression of "translational research". The Research Unit is managed by the CIEN
      Foundation, Carlos III Institute of Health, an entity depending on the Ministry
      of Science and Innovation, and financed in part by the Reina Sofia Foundation. It
      includes clinical and social research, laboratory, neuroimaging (MRI 3T), and
      biobank facilities. The connection of the Unit with other research centers and
      laboratories (both in Spain and outside), universities, and associations of AD
      patients' relatives is tight and facilitates a dynamic collaboration. The
      involvement of all social strata in the Alzheimer Project makes evident the
      unitary effort that Spain is carrying out in the fight against neurodegenerative
      diseases and, particularly, AD.

PMID- 20693622
TI  - CYP46A1 functional promoter haplotypes decipher genetic susceptibility to
      Alzheimer's disease.
AB  - We here demonstrate that promoter polymorphisms rs8003602 and rs3783320 of
      cholesterol 24S-hydroxylase (CYP46A1) were significantly associated with
      Alzheimer's disease (AD) in Chinese subjects. Haplotype analyses showed that
      haplotype CG is the risk haplotype. Either single marker or haplotypic
      association was found only in the APOE epsilon4 negative group. The association
      was then replicated in an independent set of case-control samples in Mongolians.
      We also investigated the function of promoter haplotypes and found that
      luciferase expression for TA promoter construct exhibited significantly higher
      expression level than the risk CG promoter construct. This finding might indicate
      individuals bearing the CG haplotype are genetically more susceptible to AD
      compared to those with TA haplotype. Further, we found MYT1 could be the
      potential transcription factor binding to the significant promoter polymorphism
      and mediated gene transcriptional activity. In general, our results show that
      promoter haplotypes could significantly affect CYP46A1 gene transcription level
      possibly through interacting with certain transcription factors.

PMID- 20693628
TI  - Dietary unsaturated fatty acids and risk of mild cognitive impairment.
AB  - An increasing body of epidemiological evidence suggested that elevated saturated
      fatty acids could have negative effects on age-related cognitive decline (ARCD)
      and mild cognitive impairment (MCI). Furthermore, a clear reduction of risk for
      cognitive decline has been found in population samples with elevated fish
      consumption, high intake of monounsaturated fatty acids, and polyunsaturated
      fatty acids (PUFA), particularly n-3 PUFA. In the present article, on the basis
      of increasing body of evidence from cross-sectional and longitudinal population
      based studies, we discussed the issue of the possible impact of dietary PUFA
      (both n-6 and n-3) on ARCD, MCI, and Alzheimer's disease.

PMID- 20693630
TI  - Deficiency of the copper chaperone for superoxide dismutase increases amyloid
      beta production.
AB  - The copper chaperone for superoxide dismutase (CCS) binds to both the beta-site
      AbetaPP cleaving enzyme (BACE1) and to the neuronal adaptor protein X11alpha.
      BACE1 initiates AbetaPP processing to produce the amyloid-beta (Abeta) peptide
      deposited in the brains of Alzheimer's disease patients. X11alpha also interacts
      directly with AbetaPP to inhibit Abeta production. However, whether CCS affects
      AbetaPP processing and Abeta production is not known. Here we show that loss of
      CCS increases Abeta production in both CCS knockout neurons and CCS siRNA-treated
      SHSY5Y cells and that this involves increased AbetaPP processing at the BACE1
      site.

PMID- 20693631
TI  - Is the urea cycle involved in Alzheimer's disease?
AB  - Since previous observations indicated that the urea cycle may have a role in the
      Alzheimer's disease (AD) process, we set out to quantify the expression of each
      gene involved in the urea cycle in control and AD brains and establish whether
      these genes could be genetic determinants of AD. We first confirmed that all the
      urea cycle enzyme genes are expressed in the AD brain. The expression of arginase
      2 was greater in the AD brain than in the control brain. The presence of the rare
      arginase 2 allele rs742869 was associated with an increase in the risk of AD in
      men and with an earlier age-at-onset for both genders. None of the other genes in
      the pathway appeared to be differentially expressed in the AD brain or act as
      genetic determinants of the disease.

PMID- 20693633
TI  - Effect of APOE epsilon4 allele on cortical thicknesses and volumes: the
      AddNeuroMed study.
AB  - The apolipoprotein E (APOE) epsilon4 allele is a risk factor for Alzheimer's
      disease (AD), but its effect on brain volumes is controversial. We explored the
      effect of the epsilon4 allele on regional cortical thickness and volume
      measurements using an automated pipeline in 111 subjects with mild cognitive
      impairment (MCI), 115 AD patients, and 107 age-matched healthy controls. The
      clinical data were used as covariates in the thickness and volume comparisons.
      The epsilon4 carriers had significantly smaller volume than non-carriers in
      caudate (p=0.028) in controls; in amygdala and caudate in the MCI group (p <or=
      0.049); and in hippocampus and amygdala in the AD group (p <or= 0.001). In the
      female subjects, the epsilon4 carriers had significantly thinner cortical
      thickness or smaller volume than non-carriers in medial orbitofrontal gyrus and
      caudate in controls (p <or= 0.014); in amygdala in MCI subjects (p=0.047) and in
      hippocampus and amygdala in AD patients (p <or= 0.024). However, in the male
      subjects, there were significant differences in cortical thickness and volume
      between epsilon4 carriers and non-carriers in several structures in the MCI
      group, but no differences in the controls and AD patients. Compared to the non
      carriers, the homozygous epsilon4 carriers showed significant volume loss in
      hippocampus, deep nuclei, and caudal anterior cingulate cortex in MCI. In the AD
      group, the homozygous epsilon4 carriers had significant volume loss in
      hippocampus and amygdala. We conclude that the APOE epsilon4 allele modulates
      regional cortical thickness and volume in relation to diagnostic group and
      gender. The epsilon4 allele has a dose-dependent and regionally specific effect
      on brain structures.

PMID- 20693638
TI  - An association study of 21 potential Alzheimer's disease risk genes in a Finnish
      population.
AB  - Alzheimer's disease (AD) is a genetically complex disorder encompassing several
      individual susceptibility genes with low risk effects. To assess the risk gene
      effects in a cohort consisting of ~ 1300 Finnish AD patients and controls, 21
      candidate gene polymorphisms were selected for genotyping on the basis of the
      meta-analyses retrieved from the AlzGene database. A significant genotype and
      allele association with AD was observed with rs1800629 in the tumor necrosis
      factor alpha (TNF). Risk analysis revealed a protective effect for the minor
      allele carriers of rs1800629. This suggests that genetic alteration in TNF gene
      may play a role in AD.

PMID- 20693639
TI  - A copper-lowering strategy attenuates amyloid pathology in a transgenic mouse
      model of Alzheimer's disease.
AB  - There is increasing evidence for the crucial role of metals in the pathology of
      Alzheimer's disease. Both the aggregation and neurotoxicity of amyloid-beta are
      dependent on the presence of copper. This study investigated the ability of the
      copper-complexing drug tetrathiomolybdate to reduce amyloid-beta pathology and
      spatial memory impairment in both a prevention and a treatment paradigm in the
      Tg2576 mouse model of Alzheimer's disease. Tetrathiomolybdate treatment lowered
      brain copper and reduced amyloid-beta levels in the prevention paradigm, but not
      in the treatment paradigm. Our data suggests that controlled lowering of systemic
      copper may achieve anti-amyloid effects if initiated early in the disease
      process.

PMID- 20693641
TI  - Clinically different stages of Alzheimer's disease associated by amyloid
      deposition with [11C]-PIB PET imaging.
AB  - We investigated whether [11C]-PIB PET detects underlying amyloid deposition at
      clinically different stages of Alzheimer's disease (AD) and preclinical dementia.
      The Japanese cohort of 214 subjects underwent cognitive testing and 60-min
      dynamic [11C]-PIB PET. [11C]-PIB data were acquired from 35-60 min after
      injection. Regions of interest were defined on co-registered MRI. Distribution
      volume ratios (DVR) of PIB retention were determined using Logan graphical
      analysis. All 56 patients with AD showed a robust increase in PIB retention in
      cortical areas (typical PIB AD-pattern). A mean DVR value in 11 patients with
      moderate AD (CDR: 2.1 +/- 0.4) showed significantly higher PIB retention (2.38 +/
      0.42, p < 0.01) than amyloid-negative healthy control (HC) subjects. The DVR
      values in 23 patients with very mild AD (CDR: 0.5) and 22 patients with mild AD
      (CDR: 1.0) were 2.32 +/- 0.45 and 2.34 +/- 0.42, respectively, similar to
      moderate AD. In contrast, 28 (48%) of the 58 mild cognitive impairment (MCI)
      patients (MMSE: 27.3 +/- 1.7) showed a typical AD-like pattern with a DVR value
      of 2.07 +/- 0.34. Further, 17 (18%) of 91 HC subjects had a typical AD-like
      pattern with a DVR value of 2.06 +/- 0.28. They did not significantly differ from
      very mild AD. The prevalence of AD among the 53 amyloid positive patients aged 75
      years or older increased greatly to 74% whereas that of amyloid positive HC
      decreased by only 9% and amyloid positive MCI by 17%. Prodromal AD and AD
      dementia is identified, based on cognitive function and amyloid deposition by PIB
      PET imaging. Further, the cortical amyloid deposition could be detected at
      preclinical stage of AD.

PMID- 20693656
TI  - Refined structures of placental alkaline phosphatase show a consistent pattern of
      interactions at the peripheral site.
AB  - In order to gain deeper insights into the functional sites of human placental
      alkaline phosphatase, the structures of the enzyme with the putative regulators L
      Phe, pNPP and 5'-AMP [Llinas et al. (2005), J. Mol. Biol. 350, 441-451] were re
      refined. Significant variations in ligand positioning and identity were found
      compared with the previous report. The multiple corrections to the model improved
      the phases and the electron-density maps, allowing the modeling of omitted side
      chains and multiple disordered residues. These improvements led to a change in
      the position of L-Phe at the peripheral binding site, which appeared to be
      reversed. The structure with pNPP contained only p-nitrophenol in three distinct
      sites, while the structure with 5'-AMP contained the p-nitrophenyl group in two
      of the sites instead of 5'-AMP. Comparison of the re-refined models shows a
      consistent pattern of interactions at the peripheral site.

PMID- 20693650
TI  - Ceramide-mediated insulin resistance and impairment of cognitive-motor functions.
AB  - Obesity, type 2 diabetes mellitus (T2DM), and non-alcoholic steatohepatitis
      (NASH) are associated with cognitive impairment, brain insulin resistance, and
      neurodegeneration. Recent studies linked these effects to increased pro-ceramide
      gene expression in liver and increased ceramide levels in serum. Since ceramides
      are neurotoxic and cause insulin resistance, we directly examined the role of
      ceramides as mediators of impaired signaling and central nervous system function
      using an in vivo model. Long Evans rat pups were administered C2Cer:N
      acetylsphinganine or its inactive dihydroceramide analog (C2DCer) by i.p.
      injection. Rats were subjected to rotarod and Morris water maze tests of motor
      and cognitive function, and livers and brains were examined for histopathology
      and integrity of insulin/IGF signaling. C2Cer treatment caused hyperglycemia,
      hyperlipidemia, and mild steatohepatitis, reduced brain lipid content, and
      increased ceramide levels in liver, brain, and serum. Quantitative RT-PCR
      analysis revealed significant alterations in expression of several genes needed
      for insulin and IGF-I signaling, and multiplex ELISAs demonstrated inhibition of
      signaling through the insulin or IGF-1 receptors, IRS-1, and Akt in both liver
      and brain. Ultimately, the toxic ceramides generated in peripheral sources such
      as liver or adipose tissue caused sustained impairments in neuro-cognitive
      function and insulin/IGF signaling needed for neuronal survival, plasticity, and
      myelin maintenance in the brain. These findings support our hypothesis that a
      liver/peripheral tissue-brain axis of neurodegeneration, effectuated by increased
      toxic lipid/ceramide production and transport across the blood-brain barrier,
      could mediate cognitive impairment in T2DM and NASH.

PMID- 20693657
TI  - Purification and crystallization of human Cu/Zn superoxide dismutase
      recombinantly produced in the protozoan Leishmania tarentolae.
AB  - The rapid and inexpensive production of high-quality eukaryotic proteins in
      recombinant form still remains a challenge in structural biology. Here, a protein
      expression system based on the protozoan Leishmania tarentolae was used to
      produce human Cu/Zn superoxide dismutase (SOD1) in recombinant form. Sequential
      integration of the SOD1 expression cassettes was demonstrated to lead to a linear
      increase in expression levels to up to 30 mg per litre. Chromatographic
      purification resulted in 90% pure recombinant protein, with a final yield of 6.5
      mg per litre of culture. The protein was crystallized and the structures of two
      new crystal forms were determined. These results demonstrate the suitability of
      the L. tarentolae expression system for structural research.

PMID- 20693658
TI  - Structure of a fibronectin type III-like module from Clostridium thermocellum.
AB  - The 1.6 A resolution structure of a fibronectin type III-like module from
      Clostridium thermocellum (PDB code 3mpc) with two molecules in the asymmetric
      unit is reported. The crystals used for data collection belonged to space group
      P2(1)2(1)2(1), with unit-cell parameters a=35.43, b=45.73, c=107.72 A, and the
      structure was refined to an R factor of 0.166. Structural comparisons found over
      800 similar structures in the Protein Data Bank. The broad range of different
      proteins or protein domains with high structural similarity makes it especially
      demanding to classify these proteins. Previous studies of fibronectin type III
      like modules have indicated that they might function as ligand-binding modules,
      as a compact form of peptide linkers or spacers between other domains, as
      cellulose-disrupting modules or as proteins that help large enzyme complexes
      remain soluble.

PMID- 20693659
TI  - Structural studies of the catalytic core of the primate foamy virus (PFV-1)
      integrase.
AB  - Retroviral integrases are vital enzymes in the viral life cycle and thus are
      important targets for antiretroviral drugs. The structure of the catalytic core
      domain of the integrase from human foamy virus, which is related to HIV-1, has
      been solved. The structure of the protein is presented in two different crystal
      forms, each containing several molecules in the asymmetric unit, with and without
      the essential manganese or magnesium ion, and the structures are compared in
      detail. This allows regions of high structural variability to be pinpointed, as
      well as the effect of divalent cations on the conformation of the catalytic site.

PMID- 20693661
TI  - Structures of hypoxanthine-guanine phosphoribosyltransferase (TTHA0220) from
      Thermus thermophilus HB8.
AB  - Hypoxanthine-guanine phosphoribosyltransferase (HGPRTase), which is a key enzyme
      in the purine-salvage pathway, catalyzes the synthesis of IMP or GMP from alpha-D
      phosphoribosyl-1-pyrophosphate and hypoxanthine or guanine, respectively.
      Structures of HGPRTase from Thermus thermophilus HB8 in the unliganded form, in
      complex with IMP and in complex with GMP have been determined at 2.1, 1.9 and 2.2
      A resolution, respectively. The overall fold of the IMP complex was similar to
      that of the unliganded form, but the main-chain and side-chain atoms of the
      active site moved to accommodate IMP. The overall folds of the IMP and GMP
      complexes were almost identical to each other. Structural comparison of the T.
      thermophilus HB8 enzyme with 6-oxopurine PRTases for which structures have been
      determined showed that these enzymes can be tentatively divided into groups I and
      II and that the T. thermophilus HB8 enzyme belongs to group I. The group II
      enzymes are characterized by an N-terminal extension with additional secondary
      elements and a long loop connecting the second alpha-helix and beta-strand
      compared with the group I enzymes.

PMID- 20693660
TI  - Structure of uracil-DNA glycosylase from Mycobacterium tuberculosis: insights
      into interactions with ligands.
AB  - Uracil N-glycosylase (Ung) is the most thoroughly studied of the group of uracil
      DNA-glycosylase (UDG) enzymes that catalyse the first step in the uracil excision
      repair pathway. The overall structure of the enzyme from Mycobacterium
      tuberculosis is essentially the same as that of the enzyme from other sources.
      However, differences exist in the N- and C-terminal stretches and some catalytic
      loops. Comparison with appropriate structures indicate that the two-domain enzyme
      closes slightly when binding to DNA, while it opens slightly when binding to the
      proteinaceous inhibitor Ugi. The structural changes in the catalytic loops on
      complexation reflect the special features of their structure in the mycobacterial
      protein. A comparative analysis of available sequences of the enzyme from
      different sources indicates high conservation of amino-acid residues in the
      catalytic loops. The uracil-binding pocket in the structure is occupied by a
      citrate ion. The interactions of the citrate ion with the protein mimic those of
      uracil, in addition to providing insights into other possible interactions that
      inhibitors could be involved in.

PMID- 20693662
TI  - Expression, purification, crystallization and preliminary X-ray crystallographic
      data from TktA, a transketolase from the lactic acid bacterium Lactobacillus
      salivarius.
AB  - The enzyme transketolase from the lactic acid bacterium Lactobacillus salivarius
      (subsp. salivarius UCC118) has been recombinantly expressed and purified using an
      Escherichia coli expression system. Purified transketolase from L. salivarius has
      been crystallized using the vapour-diffusion technique. The crystals belonged to
      the trigonal space group P3(2)21, with unit-cell parameters a=b=75.43, c=184.11
      A, and showed diffraction to 2.3 A resolution.

PMID- 20693663
TI  - Cloning, purification, crystallization and preliminary crystallographic analysis
      of the tandem tudor domain of Sgf29 from Saccharomyces cerevisiae.
AB  - The protein Sgf29 has been identified as a subunit of the SAGA (Spt-Ada-Gcn5
      acetyltransferase) histone acetyltransferase complex in Saccharomyces cerevisiae,
      which is conserved from yeast to humans. The tandem tudor domain at the C
      terminus of Sgf29 was crystallized using the hanging-drop vapour-diffusion method
      and the crystals diffracted to 1.92 A resolution. The crystals belonged to space
      group P2(1)2(1)2(1), with unit-cell parameters a=49.76, b=95.10, c=114.43 A, and
      are estimated to contain one protein molecule per asymmetric unit.

PMID- 20693664
TI  - Overexpression, crystallization and preliminary X-ray crystallographic analysis
      of Pseudomonas aeruginosa MnmE, a GTPase involved in tRNA modification.
AB  - MnmE, an evolutionarily conserved GTPase, is involved in modification of the
      uridine base (U34) at the wobble position of certain tRNAs. Previous crystal
      structures of MnmE suggest that it is a dimer with considerable conformational
      flexibility. To facilitate structural comparisons among MnmE proteins, structural
      analysis of MnmE from Pseudomonas aeruginosa encoded by the PA5567 gene was
      initiated. It was overexpressed in Escherichia coli and crystallized at 297 K
      using a reservoir solution consisting of 100 mM sodium ADA pH 6.5, 12%(w/v)
      polyethylene glycol 4000, 100 mM lithium sulfate, 2%(v/v) 2-propanol and 2.5 mM
      dithiothreitol. X-ray diffraction data were collected to 2.69 A resolution. The
      crystals belonged to the orthorhombic space group C222(1), with unit-cell
      parameters a=96.74, b=204.66, c=120.90 A. Two monomers were present in the
      asymmetric unit, resulting in a crystal volume per protein mass (VM) of 2.99 A3
      Da(-1) and a solvent content of 58.8%.

PMID- 20693665
TI  - Cloning, expression, purification, crystallization and preliminary X-ray
      diffraction analysis of SAICAR synthase from Streptococcus suis serotype 2.
AB  - Phosphoribosylaminoimidazole-succinocarboxamide synthase (SAICAR synthase) plays
      an essential role in the de novo biosynthesis of purine nucleotides. In this
      study, the SAICAR synthase from Streptococcus suis was cloned and overexpressed
      in Escherichia coli. The subsequent product was purified and crystallized using
      the hanging-drop vapour-diffusion method. The crystals diffracted to 2.8 A
      resolution and belonged to space group P2, with unit-cell parameters a=70.2,
      b=52.2, c=153.9 A, beta=102.8 degrees.

PMID- 20693666
TI  - Cloning, purification, crystallization and preliminary crystallographic analysis
      of LsrR from Escherichia coli.
AB  - In Escherichia coli, the lsr operon is composed of six genes lsrACDBFG which
      regulate uptake and modification of the signalling molecule AI-2. LsrR is a
      repressor of the lsr operon and itself, which can bind phospho-AI-2 and be
      released from the promoter region of the operon and thus activate gene
      expression. LsrR fused with an HHHHHH sequence at the C-terminus was expressed,
      purified and crystallized in order to determine its structure and elucidate the
      molecular mechanism of repression. The crystal belonged to space group I222, with
      unit-cell parameters a=79.84, b=116.65, c=186.04 A, and was estimated to contain
      two protein molecules per asymmetric unit.

PMID- 20693667
TI  - Expression, crystallization and preliminary X-ray diffraction analysis of the
      CMM2 region of the Arabidopsis thaliana Morpheus' molecule 1 protein.
AB  - Of the known epigenetic control regulators found in plants, the Morpheus'
      molecule 1 (MOM1) protein is atypical in that the deletion of MOM1 does not
      affect the level of epigenetic marks controlling the transcriptional status of
      the genome. A short 197-amino-acid fragment of the MOM1 protein sequence can
      complement MOM1 deletion when coupled to a nuclear localization signal,
      suggesting that this region contains a functional domain that compensates for the
      loss of the full-length protein. Numerous constructs centred on the highly
      conserved MOM1 motif 2 (CMM2) present in these 197 residues have been generated
      and expressed in Escherichia coli. Following purification and crystallization
      screening, diamond-shaped single crystals were obtained that diffracted to
      approximately 3.2 A resolution. They belonged to the trigonal space group P3(1)21
      (or P3(2)21), with unit-cell parameters a=85.64, c=292.74 A. Structure
      determination is ongoing.

PMID- 20693668
TI  - Expression, purification and preliminary crystallization of amaranth 11S
      proglobulin seed storage protein from Amaranthus hypochondriacus L.
AB  - 11S globulin is one of the major seed storage proteins in amaranth. Recombinant
      protein was produced as up to approximately 80% of the total bacterial protein
      using Escherichia coli Rosetta-gami (DE3) containing pET21d with amaranth 11S
      globulin cDNA. The best expression condition was at 302 K for 20 h using LB
      medium containing 0.5 M NaCl. The recombinant protein was easily separated from
      most of the Escherichia coli proteins by precipitation with 0-40% ammonium
      sulfate solution. It formed aggregates at low temperature and at low salt
      concentrations. This behaviour may imply that it has a more hydrophobic nature
      than other 11S seed globulins. The crystals diffracted to 6 A resolution and
      belonged to space group P6(3), with unit-cell parameters a=b=97.6, c=74.8 A,
      gamma=120.0 degrees. One subunit of a trimer was estimated to be present in the
      asymmetric unit, assuming a Vsol of 41%. To obtain the complete structure
      solution, experiments to improve crystallization and flash-cooling conditions are
      in progress.

PMID- 20693669
TI  - Crystallization and preliminary X-ray crystallographic studies of omega
      transaminase from Vibrio fluvialis JS17.
AB  - Omega-transaminase (omega-TA) catalyzes the transfer of an amino group from a non
      alpha-position amino acid or an amine compound with no carboxylic group to an
      amino acceptor. omega-TA from Vibrio fluvialis JS17 (omega-TAVf) is a novel
      amine:pyruvate transaminase that is capable of stereoselective transamination of
      aryl chiral amines. In this study, omega-TAVf was overexpressed in Escherichia
      coli with engineered C-terminal His tags. omega-TAVf was then purified to
      homogeneity and crystallized at 292 K. X-ray diffraction data were collected to a
      resolution of 2.5 A from a crystal belonging to the orthorhombic space group
      P2(1)2(1)2(1), with unit-cell parameters a=78.43, b=95.95, c=122.89 A.

PMID- 20693670
TI  - Cloning, purification, crystallization and preliminary X-ray crystallographic
      analysis of SET/TAF-Ibeta deltaN from Homo sapiens.
AB  - The histone chaperone SET encoded by the SET gene, which is also known as
      template-activating factor Ibeta (TAF-Ibeta), is a multifunctional molecule that
      is involved in many biological phenomena such as histone binding, nucleosome
      assembly, chromatin remodelling, replication, transcription and apoptosis. A
      truncated SET/TAF-Ibeta DeltaN protein that lacked the first 22 residues of the N
      terminus but contained the C-terminal acidic domain and an additional His6 tag at
      the C-terminus was overexpressed in Escherichia coli and crystallized by the
      hanging-drop vapour-diffusion method using sodium acetate as precipitant at 283
      K. The crystals diffracted to 2.7 A resolution and belonged to space group
      P4(3)2(1)2.

PMID- 20693671
TI  - Crystallization and preliminary crystallographic studies of the C-terminal domain
      of outer membrane protein A from enterohaemorrhagic Escherichia coli.
AB  - Outer membrane protein A (OmpA) of enterohaemorrhagic Escherichia coli (EHEC)
      plays multiple roles in bacterial physiology and pathogenesis, such as mediation
      of bacterial conjunction, maintenance of cell shape, induction of adhesion of
      EHEC to host cells etc. Better understanding of the functions of OmpA will help
      in the control of EHEC infections. OmpA is composed of two domains: the N
      terminal domain and the C-terminal domain. The N-terminal domain is a beta-barrel
      structure and embeds in the outer membrane of the bacterium. The structure and
      function of the C-terminal domain of OmpA (OmpAC) remain elusive. In this study,
      recombinant OmpAC from EHEC was purified and crystallized and a diffraction data
      set was collected to 2.7 A resolution. The crystals belonged to space group
      I4(1)32, with unit-cell parameter a=158.99 A. The Matthews coefficient and
      solvent content were calculated to be 2.55 A3 Da(-1) and 51.77%, respectively,
      for two molecules in the asymmetric unit.

PMID- 20693672
TI  - Crystallization and preliminary crystallographic analysis of the ADP
      ribosyltransferase HopU1.
AB  - Several Gram-negative pathogens of plants and animals and some eukaryotic
      associated bacteria use type III protein-secretion systems (T3SSs) to deliver
      bacterial virulence-associated ;effector' proteins directly into host cells.
      HopU1 is a type III effector protein from the plant pathogen Pseudomonas
      syringae, which causes plant bacterial speck disease. HopU1 quells host immunity
      through ADP-ribosylation of GRP7 as a substrate. HopU1 has been reported as the
      first ADP-ribosyltransferase virulence protein to be identified in a plant
      pathogen. Although several structures of ADP-ribosyltransferases have been
      determined to date, no structure of an ADP-ribosyltransferase from a plant
      pathogen has been determined. Here, the protein expression, purification,
      crystallization and preliminary crystallographic analysis of HopU1 are reported.
      Diffracting crystals were grown by hanging-drop vapour diffusion using
      polyethylene glycol 10,000 as a precipitant. Native and SAD data sets were
      collected using native and selenomethionine-derivative HopU1 crystals. The
      diffraction pattern of the crystal extended to 2.7 A resolution using synchrotron
      radiation. The crystals belonged to space group P4(3), with unit-cell parameters
      a=92.6, b=92.6, c=101.6 A.

PMID- 20693673
TI  - Crystallization and preliminary X-ray crystallographic studies of human FAIM
      protein.
AB  - Fas apoptosis inhibitory molecule (FAIM), an antagonist of Fas-induced cell
      death, is highly conserved and is broadly expressed in many tissues. It has been
      found that FAIM can stimulate neurite outgrowth in PC12 cells and primary
      neurons. However, the molecular mechanisms of action of FAIM are not understood
      in detail. Here, full-length human FAIM and two truncation constructs have
      successfully been cloned, expressed and purified in Escherichia coli. FAIM (1-90)
      was crystallized and diffracted to a resolution of 2.5 A; the crystal belonged to
      space group P3(1), with unit-cell parameters a=b=58.02, c=71.11 A, alpha=beta=90,
      gamma=120 degrees. There were two molecules in the asymmetric unit.

PMID- 20693674
TI  - Expression, purification, crystallization and preliminary X-ray studies of
      Lactobacillus jensenii enolase.
AB  - Recombinant Lactobacillus jensenii enolase fused to a C-terminal noncleavable His
      tag was expressed in Escherichia coli, purified and crystallized by sitting-drop
      vapor diffusion. A complete data set was collected to 3.25 A resolution. The
      crystals belonged to space group I4, with unit-cell parameters a=b=145.31,
      c=99.79 A. There were two protein subunits in the asymmetric unit, which gave a
      Matthews coefficient VM of 2.8 A3 Da(-1), corresponding to 55.2% solvent content.

PMID- 20693675
TI  - Overexpression, crystallization and preliminary X-ray analysis of xylulose-5
      phosphate/fructose-6-phosphate phosphoketolase from Bifidobacterium breve.
AB  - The xylulose-5-phosphate/fructose-6-phosphate phosphoketolase gene from
      Bifidobacterium breve was cloned and overexpressed in Escherichia coli. The
      enzyme was purified to homogeneity and crystallized by the sitting-drop vapour
      diffusion method. Crystals were obtained at 293 K using 0.05 mM thiamine
      diphosphate, 0.25 mM MgCl2, 24%(w/v) PEG 6000 and 0.1 M Bicine pH 9.0. The
      crystals belonged to the tetragonal space group I422, with unit-cell parameters
      a=b=174.8, c=163.8 A, and diffracted to beyond 1.7 A resolution.

PMID- 20693676
TI  - Cloning, overexpression, purification, crystallization and preliminary X-ray
      analysis of CheY3, a response regulator that directly interacts with the
      flagellar 'switch complex' in Vibrio cholerae.
AB  - Vibrio cholerae is the aetiological agent of the severe diarrhoeal disease
      cholera. This highly motile organism uses the processes of motility and
      chemotaxis to travel and colonize the intestinal epithelium. Chemotaxis in V.
      cholerae is far more complex than that in Escherichia coli or Salmonella
      typhimurium, with multiple paralogues of various chemotaxis genes. In contrast to
      the single copy of the chemotaxis response-regulator protein CheY in E. coli, V.
      cholerae contains four CheYs (CheY1-CheY4), of which CheY3 is primarily
      responsible for interacting with the flagellar motor protein FliM, which is one
      of the major constituents of the ;switch complex' in the flagellar motor. This
      interaction is the key step that controls flagellar rotation in response to
      environmental stimuli. CheY3 has been cloned, overexpressed and purified by Ni
      NTA affinity chromatography followed by gel filtration. Crystals of CheY3 were
      grown in space group R3, with a calculated Matthews coefficient of 2.33 A3 Da(-1)
      (47% solvent content) assuming the presence of one molecule per asymmetric unit.

PMID- 20693677
TI  - Expression, purification and crystallization of a plant type III polyketide
      synthase that produces diarylheptanoids.
AB  - Curcuminoid synthase (CUS) from Oryza sativa is a plant-specific type III
      polyketide synthase that catalyzes the one-pot formation of bisdemethoxycurcumin
      by the condensation of two molecules of 4-coumaroyl-CoA and one molecule of
      malonyl-CoA. Recombinant CUS was expressed in Escherichia coli and crystallized
      by the sitting-drop vapour-diffusion method. The crystals belonged to space group
      P2(1), with unit-cell parameters a=72.7, b=97.2, c=126.2 A, alpha=gamma=90.0,
      beta=103.7 degrees. A diffraction data set was collected in-house to 2.5 A
      resolution.

PMID- 20693678
TI  - Crystallization and preliminary X-ray diffraction analysis of the putative aldose
      1-epimerase YeaD from Escherichia coli.
AB  - Escherichia coli YeaD (ecYeaD) is suggested to be a member of the galactose
      mutarotase-like superfamily. Galactose mutarotase is an enzyme that converts
      alpha-galactose to beta-galactose. The known structures of these galactose
      mutarotase-like proteins are similar to those of galactose mutarotases, with the
      catalytic residues being conserved, but there are some differences between them
      in the substrate-binding pocket. In order to reveal the specificity of ecYeaD, a
      three-dimensional structure is essential. Full-length ecYeaD with an additional
      6xHis tag at the C-terminus was crystallized by the hanging-drop vapour-diffusion
      method using polyethylene glycol 4000 as a precipitant at 283 K. An X-ray
      diffraction data set was collected to a resolution of 1.9 A from a single flash
      cooled crystal that belonged to space group P2(1)2(1)2(1).

PMID- 20693679
TI  - Crystallization and preliminary X-ray analysis of tubulin-folding cofactor A from
      Arabidopsis thaliana.
AB  - Tubulin-folding cofactor A (TFC A) is a molecular post-chaperonin that is
      involved in the beta-tubulin-folding pathway. It has been identified in many
      organisms including yeasts, humans and plants. In this work, Arabidopsis thaliana
      TFC A was expressed in Escherichia coli and purified to homogeneity. After
      thrombin cleavage, a well diffracting crystal was obtained by the sitting-drop
      vapour-diffusion method at 289 K. The crystal diffracted to 1.6 A resolution
      using synchrotron radiation and belonged to space group I4(1), with unit-cell
      parameters a=55.0, b=55.0, c=67.4 A.

PMID- 20693681
TI  - Crystallization and preliminary X-ray analysis of the complex of human alpha
      thrombin with a modified thrombin-binding aptamer.
AB  - The thrombin-binding aptamer (TBA) is a consensus DNA 15-mer that binds
      specifically to human alpha-thrombin at nanomolar concentrations and inhibits its
      procoagulant functions. Recently, a modified TBA (mTBA) containing a 5'-5'
      inversion-of-polarity site has been shown to be more stable and to possess a
      higher thrombin affinity than its unmodified counterpart. The structure of the
      thrombin-TBA complex has previously been determined at low resolution, but did
      not provide a detailed picture of the aptamer conformation or of the protein-DNA
      assembly, while that of the complex with mTBA is unknown. Crystallographic
      analysis of the thrombin-mTBA complex has been attempted. The crystals diffracted
      to 2.15 A resolution and belonged to space group I222.

PMID- 20693680
TI  - Crystallization and preliminary X-ray diffraction analysis of Pseudomonas
      aeruginosa phosphorylcholine phosphatase.
AB  - Pseudomonas aeruginosa phosphorylcholine phosphatase (PchP) catalyzes the
      hydrolysis of phosphorylcholine to produce choline and inorganic phosphate.
      Phosphorylcholine is released by the action of haemolytic phospholipase C (PlcH)
      on phosphatidylcholine or sphingomyelin. PchP belongs to the HAD superfamily and
      its activity is dependent on Mg2+, Zn2+ or Cu2+. The possible importance of PchP
      in the pathogenesis of P. aeruginosa, the lack of information about its structure
      and its low identity to other members of this family led us to attempt its
      crystallization in order to solve its three-dimensional structure. Crystals of
      the protein have been grown and diffraction data have been obtained to 2.7 A
      resolution. The crystals belonged to the monoclinic space group C2, with unit
      cell parameters a=137.16, b=159.15, c=73.31 A, beta=117.89 degrees. Statistical
      analysis of the unit-cell contents and the self-rotation function suggest a
      tetrameric state of the molecule with 222 point-group symmetry.

PMID- 20693682
TI  - Crystallization of BMP receptor type IA bound to the antibody Fab fragment
      AbD1556.
AB  - An antibody Fab fragment, AbD1556, was selected against the extracellular domain
      of BMP receptor type IA, which blocks the binding of BMP-2 to BMPR-IA and thereby
      neutralizes BMP-2 activity. To study the mechanism by which BMPR-IA is recognized
      and bound by the Fab fragment, the complex of AbD1556 bound to BMPR-IA was
      prepared and crystallized. Crystals of this binary complex belonged to the
      monoclinic space group P2(1), with unit-cell parameters a=89.32, b=129.25,
      c=100.24 A, beta=92.27 degrees.

PMID- 20693683
TI  - Laser-improved protein crystallization screening.
AB  - Screening of proteins for crystallization under laser irradiation was
      investigated using six proteins: ribonuclease B, glucose dehydrogenase, lysozyme,
      sorbitol dehydrogenase, fructose dehydrogenase and myoglobin. Shining 532 nm
      green circularly polarized laser light with a picosecond pulse and 6 mW power for
      30 s on newly set-up protein drops showed a marked improvement in the number of
      screen conditions amenable for crystal growth compared with control drops under
      identical conditions but without laser exposure. For glucose dehydrogenase and
      sorbitol dehydrogenase, larger and better quality crystals were formed and the
      resolution of X-ray diffraction was improved. The speed of crystallization
      increased in the case of ribonuclease B, lysozyme and sorbitol dehydrogenase.
      During laser irradiation, the amount of precipitation in the screened drops
      increased, indicating a transient decrease in protein solubility. At the
      optimized laser settings, there was no deleterious effect of the laser on crystal
      growth or on the protein. In the cases of ribonuclease B and lysozyme the crystal
      packing did not change owing to the laser exposure.

PMID- 20693684
TI  - Diffraction cartography: applying microbeams to macromolecular crystallography
      sample evaluation and data collection.
AB  - Crystals of biological macromolecules often exhibit considerable inter-crystal
      and intra-crystal variation in diffraction quality. This requires the evaluation
      of many samples prior to data collection, a practice that is already widespread
      in macromolecular crystallography. As structural biologists move towards tackling
      ever more ambitious projects, new automated methods of sample evaluation will
      become crucial to the success of many projects, as will the availability of
      synchrotron-based facilities optimized for high-throughput evaluation of the
      diffraction characteristics of samples. Here, two examples of the types of
      advanced sample evaluation that will be required are presented: searching within
      a sample-containing loop for microcrystals using an X-ray beam of 5 microm
      diameter and selecting the most ordered regions of relatively large crystals
      using X-ray beams of 5-50 microm in diameter. A graphical user interface
      developed to assist with these screening methods is also presented. For the case
      in which the diffraction quality of a relatively large crystal is probed using a
      microbeam, the usefulness and implications of mapping diffraction-quality
      heterogeneity (diffraction cartography) are discussed. The implementation of
      these techniques in the context of planned upgrades to the ESRF's structural
      biology beamlines is also presented.

PMID- 20693685
TI  - Structure of the N-terminal fragment of Escherichia coli Lon protease.
AB  - The structure of a recombinant construct consisting of residues 1-245 of
      Escherichia coli Lon protease, the prototypical member of the A-type Lon family,
      is reported. This construct encompasses all or most of the N-terminal domain of
      the enzyme. The structure was solved by SeMet SAD to 2.6 A resolution utilizing
      trigonal crystals that contained one molecule in the asymmetric unit. The
      molecule consists of two compact subdomains and a very long C-terminal alpha
      helix. The structure of the first subdomain (residues 1-117), which consists
      mostly of beta-strands, is similar to that of the shorter fragment previously
      expressed and crystallized, whereas the second subdomain is almost entirely
      helical. The fold and spatial relationship of the two subdomains, with the
      exception of the C-terminal helix, closely resemble the structure of BPP1347, a
      203-amino-acid protein of unknown function from Bordetella parapertussis, and
      more distantly several other proteins. It was not possible to refine the
      structure to satisfactory convergence; however, since almost all of the Se atoms
      could be located on the basis of their anomalous scattering the correctness of
      the overall structure is not in question. The structure reported here was also
      compared with the structures of the putative substrate-binding domains of several
      proteins, showing topological similarities that should help in defining the
      binding sites used by Lon substrates.

PMID- 20693686
TI  - The first crystal structure of a gramicidin complex with sodium: high-resolution
      study of a nonstoichiometric gramicidin D-NaI complex.
AB  - The crystal structure of the nonstoichiometric complex of gramicidin D with NaI
      has been studied using synchrotron radiation at 100 K. The limiting resolution
      was 1.25 A and the R factor was 16% for 19 883 observed reflections. The general
      architecture of the antiparallel two-stranded gramicidin dimers in the studied
      crystal was a right-handed antiparallel double-stranded form that closely
      resembles the structures of other right-handed species published to date.
      However, there were several surprising observations. In addition to the
      significantly different composition of linear gramicidins identified in the
      crystal structure, including the absence of the gramicidin C form, only two
      cationic sites were found in each of the two independent dimers (channels), which
      were partially occupied by sodium, compared with the seven sites found in the
      RbCl complex of gramicidin. The sum of the partial occupancies of Na(+) was only
      1.26 per two dimers and was confirmed by the similar content of iodine ions (1.21
      ions distributed over seven sites), which was easily visible from their anomalous
      signal. Another surprising observation was the significant asymmetry of the
      distributions and occupancies of cations in the gramicidin dimers, which was in
      contrast to those observed in the high-resolution structures of the complexes of
      heavier alkali metals with gramicidin D, especially that of rubidium.

PMID- 20693687
TI  - Structure of Staphylococcus aureus adenylosuccinate lyase (PurB) and assessment
      of its potential as a target for structure-based inhibitor discovery.
AB  - The medium-resolution structure of adenylosuccinate lyase (PurB) from the
      bacterial pathogen Staphylococcus aureus in complex with AMP is presented.
      Oxalate, which is likely to be an artifact of crystallization, has been modelled
      in the active site and occupies a position close to that where succinate is
      observed in orthologous structures. PurB catalyzes reactions that support the
      provision of purines and the control of AMP/fumarate levels. As such, the enzyme
      is predicted to be essential for the survival of S. aureus and to be a potential
      therapeutic target. Comparisons of this pathogen PurB with the enzyme from
      Escherichia coli are presented to allow discussion concerning the enzyme
      mechanism. Comparisons with human PurB suggest that the close similarity of the
      active sites would make it difficult to identify species-specific inhibitors for
      this enzyme. However, there are differences in the way that the subunits are
      assembled into dimers. The distinct subunit-subunit interfaces may provide a
      potential area to target by exploiting the observation that creation of the
      enzyme active site is dependent on oligomerization.

PMID- 20693688
TI  - Validation of crystallographic models containing TLS or other descriptions of
      anisotropy.
AB  - The use of TLS (translation/libration/screw) models to describe anisotropic
      displacement of atoms within a protein crystal structure has become increasingly
      common. These models may be used purely as an improved methodology for
      crystallographic refinement or as the basis for analyzing inter-domain and other
      large-scale motions implied by the crystal structure. In either case it is
      desirable to validate that the crystallographic model, including the TLS
      description of anisotropy, conforms to our best understanding of protein
      structures and their modes of flexibility. A set of validation tests has been
      implemented that can be integrated into ongoing crystallographic refinement or
      run afterwards to evaluate a previously refined structure. In either case
      validation can serve to increase confidence that the model is correct, to
      highlight aspects of the model that may be improved or to strengthen the evidence
      supporting specific modes of flexibility inferred from the refined TLS model.
      Automated validation checks have been added to the PARVATI and TLSMD web servers
      and incorporated into the CCP4i user interface.

PMID- 20693689
TI  - Quantitive evaluation of macromolecular crystallization experiments using 1,8-ANS
      fluorescence.
AB  - Modern X-ray structure analysis and advances in high-throughput robotics have
      allowed a significant increase in the number of conditions screened for a given
      sample volume. An efficient evaluation of the increased amount of crystallization
      trials in order to identify successful experiments is now urgently required. A
      novel approach is presented for the visualization of crystallization experiments
      using fluorescence from trace amounts of a nonspecific dye. The fluorescence
      images obtained strongly contrast protein crystals against other phenomena, such
      as precipitation and phase separation. Novel software has been developed to
      quantitatively evaluate the crystallization outcome based on a biophysical metric
      correlated with voxel protein concentration. In >1500 trials, 85.6% of the
      successful crystallization experiments were correctly identified, yielding a 50%
      reduction in the number of 'missed hits' compared with current automated
      approaches. The use of the method in the crystallization of three previously
      uncharacterized proteins from the malarial parasite Plasmodium falciparum is
      further demonstrated.

PMID- 20693690
TI  - Structural and functional analysis of Rv0554 from Mycobacterium tuberculosis:
      testing a putative role in menaquinone biosynthesis.
AB  - Mycobacterium tuberculosis, the cause of tuberculosis, is a devastating human
      pathogen against which new drugs are urgently needed. Enzymes from the
      biosynthetic pathway for menaquinone are considered to be valid drug targets. The
      protein encoded by the open reading frame Rv0554 has been expressed, purified and
      subjected to structural and functional analysis to test for a putative role in
      menaquinone biosynthesis. The crystal structure of Rv0554 has been solved and
      refined in two different space groups at 2.35 and 1.9 A resolution. The protein
      is dimeric, with an alpha/beta-hydrolase monomer fold. In each monomer, a large
      cavity adjacent to the catalytic triad is enclosed by a helical lid. Dimerization
      is mediated by the lid regions. Small-molecule additives used in crystallization
      bind in the active site, but no binding of ligands related to menaquinone
      biosynthesis could be detected and functional assays failed to support possible
      roles in menaquinone biosynthesis.

PMID- 20693691
TI  - Structural basis of the histidine-mediated vitamin D receptor agonistic and
      antagonistic mechanisms of (23S)-25-dehydro-1alpha-hydroxyvitamin D3-26,23
      lactone.
AB  - TEI-9647 antagonizes vitamin D receptor (VDR) mediated genomic actions of
      1alpha,25(OH)2D3 in human cells but is agonistic in rodent cells. The presence of
      Cys403, Cys410 or of both residues in the C-terminal region of human VDR (hVDR)
      results in antagonistic action of this compound. In the complexes of TEI-9647
      with wild-type hVDR (hVDRwt) and H397F hVDR, TEI-9647 functions as an antagonist
      and forms a covalent adduct with hVDR according to MALDI-TOF MS. The crystal
      structures of complexes of TEI-9647 with rat VDR (rVDR), H305F hVDR and
      H305F/H397F hVDR showed that the agonistic activity of TEI-9647 is caused by a
      hydrogen-bond interaction with His397 or Phe397 located in helix 11. Both
      biological activity assays and the crystal structure of H305F hVDR complexed with
      TEI-9647 showed that the interaction between His305 and TEI-9647 is crucial for
      antagonist activity. This study indicates the following stepwise mechanism for
      TEI-9647 antagonism. Firstly, TEI-9647 forms hydrogen bonds to His305, which
      promote conformational changes in hVDR and draw Cys403 or Cys410 towards the
      ligand. This is followed by the formation of a 1,4-Michael addition adduct
      between the thiol (-SH) group of Cys403 or Cys410 and the exo-methylene group of
      TEI-9647.

PMID- 20693692
TI  - Promoting crystallization of antibody-antigen complexes via microseed matrix
      screening.
AB  - The application of microseed matrix screening to the crystallization of antibody
      antigen complexes is described for a set of antibodies that include mouse anti-IL
      13 antibody C836, its humanized version H2L6 and an affinity-matured variant of
      H2L6, M1295. The Fab fragments of these antibodies were crystallized in complex
      with the antigen human IL-13. The initial crystallization screening for each of
      the three complexes included 192 conditions. Only one hit was observed for H2L6
      and none were observed for the other two complexes. Matrix self-microseeding
      using these microcrystals yielded multiple hits under various conditions that
      were further optimized to grow diffraction-quality H2L6 crystals. The same H2L6
      seeds were also successfully used to promote crystallization of the other two
      complexes. The M1295 crystals appeared to be isomorphous to those of H2L6,
      whereas the C836 crystals were in a different crystal form. These results are
      consistent with the concept that the conditions that are best for crystal growth
      may be different from those that favor nucleation. Microseed matrix screening
      using either a self-seeding or cross-seeding approach proved to be a fast, robust
      and reliable method not only for the refinement of crystallization conditions but
      also to promote crystal nucleation and increase the hit rate.

PMID- 20693693
TI  - Crystallographic binding studies with an engineered monomeric variant of
      triosephosphate isomerase.
AB  - Crystallographic binding studies have been carried out to probe the active-site
      binding properties of a monomeric variant (A-TIM) of triosephosphate isomerase
      (TIM). These binding studies are part of a structure-based directed-evolution
      project aimed towards changing the substrate specificity of monomeric TIM and are
      therefore aimed at finding binders which are substrate-like molecules. A-TIM has
      a modified more extended binding pocket between loop-7 and loop-8 compared with
      wild-type TIM. The A-TIM crystals were grown in the presence of citrate, which is
      bound in the active site of each of the two molecules in the asymmetric unit. In
      this complex, the active-site loops loop-6 and loop-7 adopt the closed
      conformation, similar to that observed in liganded wild-type TIM. Extensive
      crystal-soaking protocols have been developed to flush the bound citrate out of
      the active-site pocket of both molecules and the crystal structure shows that the
      unliganded open conformation of the A-TIM active site is the same as in
      unliganded wild-type TIM. It is also shown that sulfonate compounds corresponding
      to the transition-state analogue 2-phosphoglycolate bind in the active site,
      which has a closed conformation. It is also shown that the new binding pocket of
      A-TIM can bind 3-phosphoglycerate (3PGA; an analogue of a C4-sugar phosphate) and
      4-phospho-D-erythronohydroxamic acid (4PEH; an analogue of a C5-sugar phosphate).
      Therefore, these studies have provided a rationale for starting directed
      evolution experiments aimed at generating the catalytic properties of a C5-sugar
      phosphate isomerase on the A-TIM framework.

PMID- 20693694
TI  - Enhancing MAD F(A) data for substructure determination.
AB  - Heavy-atom substructure determination is a critical step in phasing an unknown
      macromolecular structure. Dual-space (Shake-and-Bake) recycling is a very
      effective procedure for locating the substructure (heavy) atoms using F(A) data
      estimated from multiple-wavelength anomalous diffraction. However, the estimated
      F(A) are susceptible to the accumulation of errors in the individual intensity
      measurements at several wavelengths and from inaccurate estimation of the
      anomalous atomic scattering corrections f' and f''. In this paper, a new
      statistical and computational procedure which merges multiple F(A) estimates into
      an averaged data set is used to further improve the quality of the estimated
      anomalous amplitudes. The results of 18 Se-atom substructure determinations
      provide convincing evidence in favor of using such a procedure to locate
      anomalous scatterers.

PMID- 20693695
TI  - Emerging from pseudo-symmetry: the redetermination of human carbonic anhydrase II
      in monoclinic P2(1) with a doubled a axis.
AB  - The crystal structure of human carbonic anhydrase II in the monoclinic P2(1)
      space group with a doubled a axis from that of the usually observed unit cell has
      recently been reported, with one of the two molecules in the asymmetric unit
      demonstrating rotational disorder [Robbins et al. (2010), Acta Cryst. D66, 628
      634]. The structure has been redetermined, with the coordinates of both pseudo
      symmetrically related molecules in the crystallographic asymmetric unit
      translated by x' = x +/- 1/4, and no rotational disorder is observed. This
      corresponds to a different choice of how the four molecules in the unit cell
      should be grouped into pairs that represent a single asymmetric unit.

PMID- 20693696
TI  - Using item response modeling methods to test theory related to human performance.
AB  - Testing theories of human performance requires measurement of latent constructs
      like performer perception and motivation, intrinsic parts of performance, but
      nebulous to assess. Item response modeling (IRM) methods model latent constructs
      directly and thus can assist in the development and testing of theory. This
      article presents an application of IRM methods in initial testing of the Movement
      Continuum Theory. A construct was derived from the theory, and an instrument was
      generated to put the construct into operation. Over 300 people of varying
      movement abilities, aged 18 to 101, completed the 24-item Movement Ability
      Measure, a self-report questionnaire asking for participants' perceptions of
      their current and preferred ability to move. Wright Maps derived from estimated
      locations of participants and item thresholds showed the strong relationship
      between the theorized construct and the empirical data. Data gathered with the
      instrument and analyzed with IRM methods provided mixed support for principles of
      the theory.

PMID- 20693697
TI  - From model to measurement with dichotomous items.
AB  - Psychometric models typically represent encounters between persons and
      dichotomous items as a random variable with two possible outcomes, one of which
      can be labeled success. For a given item, the stipulation that each person has a
      probability of success defines a construct on persons. This model specification
      defines the construct, but measurement is not yet achieved. The path to
      measurement must involve replication; unlike coin-tossing, this cannot be
      attained by repeating the encounter between the same person and the same item.
      Such replication can only be achieved with more items whose features are included
      in the model specifications. That is, the model must incorporate multiple items.
      This chapter examines multi-item model specifications that support the goal of
      measurement. The objective is to select the model that best facilitates the
      development of reliable measuring instruments. From this perspective, the Rasch
      model has important features compared to other models.

PMID- 20693698
TI  - Using Guttman's mapping sentences and Many Facet Rasch Measurement Theory to
      develop an instrument that examines the grading philosophies of teachers.
AB  - This study presents an approach to questionnaire design within educational
      research based on Guttman's mapping sentences (Guttman, 1977) and Many-Facet
      Rasch Measurement Theory (Linacre, 1994). The primary purpose of this study was
      to illustrate how Guttman's mapping sentences can be used to develop an
      instrument that explores the grading philosophies of teachers. A secondary
      purpose was to clarify teacher grading philosophies (i.e., severity or leniency)
      as a measurement construct. We designed a 54-item questionnaire in which each
      item represented a unique combination of student characteristics, i.e., varying
      levels of classroom achievement, ability, behavior, and effort. The grades
      assigned by the teachers to the scenarios were analyzed using the FACETS
      (Linacre, 2007) computer program. The results of the analyses suggest that the
      grading philosophies of teachers represent a unidimensional construct which is
      influenced, to varying extents, by the classroom achievement (primarily),
      behavior, and effort of students; whereas the measurement value added by the
      inclusion of the ability facet is uncertain.

PMID- 20693699
TI  - Development of scales relating to professional development of community college
      administrators.
AB  - This article reports the results of an application of the Multidimensional Random
      Coefficients Multinomial Logit Model (MRCMLM) to the measurement of professional
      development activities in which community college administrators participate. The
      analyses focus on confirmation of the factorial structure of the instrument,
      evaluation of the quality of the activities calibrations, examination of the
      internal structure of the instrument, and comparison of groups of administrators.
      The dimensionality analysis results suggest a five-dimensional model that is
      consistent with previous literature concerning career paths of community college
      administrators - education and specialized training, internal professional
      development and mentoring, external professional development, employer support,
      and seniority. The indicators of the quality of the activity calibrations suggest
      that measures of the five dimensions are adequately reliable, that the activities
      in each dimension are internally consistent, and that the observed responses to
      each activity are consistent with the expected values of the MRCMLM. The
      hierarchy of administrator measure means and of activity calibrations is
      consistent with substantive theory relating to professional development for
      community college administrators. For example, readily available activities that
      occur at the institution were most likely to be engaged in by administrators,
      while participation in selective specialized training institutes were the least
      likely activities. Finally, group differences with respect to age and title were
      consistent with substantive expectations - the greater the administrator's age
      and the higher the rank of the administrator's title, the greater the probability
      of having engaged in various types of professional development.

PMID- 20693700
TI  - Comparing decalage and development with cognitive developmental tests.
AB  - The use of Rasch measurement techniques with data from developmental psychology
      has provided important insights into human development (e.g., Bond, 1997, 2003;
      Dawson, 2002 a, b;). In particular, Rasch methods support investigations into
      what has been, up until now, intractable theoretical and empirical problems.
      Research into the development of formal operational thinking using the Rasch
      model (Bond 1995 a, b; Bond and Bunting, 1995; Bond and Fox, 2001) substantiates
      important aspects of the original theorizing of Piaget (Inhelder and Piaget,
      1955/1958), which was based wholly on qualitative structural analyses of
      children's problem-solving responses. Common-person equating of student
      performances has been used across different formal operational thinking tasks to
      estimate the relative difficulties of tasks measuring the same underlying
      developmental construct (Bond, 1995b; Bond and Fox, 2001). Repeated person
      performance measures on the same task have been used in order to estimate
      cognitive development over time. Rasch measurement estimates of cognitive
      development do not exceed 0.5 logits per annum (Bond, 1996; Endler, 1998;
      Stanbridge, 2001); a result that has been estimated independently in two large
      research projects in the United Kingdom (Shayer, 1999) and in Papua-New Guinea
      (Lake, 1996). Interestingly, difficulty differences (decalage) between tests of
      formal thought are as large as 2.0 logits (Bond, 1995a; Bond, 1996; Bond and Fox,
      2001), confounding attempts to differentiate development from decalage. Given the
      problems and possibilities raised by the Rasch measurement quantification of
      cognitive development, this article canvasses the promise of using Rasch
      modelling techniques to investigate systematically these fundamental aspects of
      human cognitive performance.

PMID- 20693701
TI  - Reliability of performance examinations: revisited.
AB  - This article discusses the reliability for performance examinations with respect
      to the reproducibility of candidate pass-fail decisions. The multi-facet Rasch
      model accounts for the difficulty of test forms (examiners + tasks + items) taken
      by each candidate, so that all candidates are measured against the same
      criterion. The examiners provide analytic ratings of candidate performance using
      a defined rating scale. The examination is standardized so that sufficient
      information is collected about the candidates, and facets of the examination are
      linked. When the examination data are properly collected, there are high levels
      of confidence in the reproducibility of candidate outcomes for a high percentage
      of candidates.

PMID- 20693702
TI  - Equating designs and procedures used in Rasch scaling.
AB  - The development of alternate forms of tests requires a statistical score
      adjustment called equating that permits the interchanging of scores from
      different test forms. Equating makes possible several important measurement
      applications, including removing practice effects in pretest-posttest research
      designs, improving test security, comparing scores between new and old forms, and
      supporting item bank development for computerized adaptive testing. This article
      summarizes equating methods from a Rasch measurement perspective. The four
      sections of this article present an introduction and definition of equating and
      related linking methods, data collection designs, equating procedures, and
      evaluating equated measures. The methods are illustrated with worked examples.

PMID- 20693703
TI  - Screening for methylation-silenced genes in acute myeloid leukemia HL-60 cell
      line by a quantitative proteomic approach.
AB  - OBJECTIVE: To screen for new methylation association genes in HL-60 to reveal the
      pathogenesis of leukemia, and provide important theoretical and scientific basis
      for the prevention and cure of leukemia. METHODS: Two-dimensional fluorescence
      difference gel electrophoresis (F-2D-DIGE) was performed to separate the total
      proteins from acute myelogenous leukemia (AML) cell line HL-60 cells with or
      without 5-aza-2-deoxycytidine (5-aza-2-dC) treatment. Imaging software Decyder
      6.5 and PDQuest were used to detect the differential expression protein spots,
      and matrix-assisted laser desorption/ionizaion time-of-flight mas spectrometer
      (MALDI-TOF MS) was adopted to identify the differential expression proteins.
      RESULTS: F-2D-DIGE maps of 5-aza-2-dC-untreated HL-60 and-treated HL-60 cells
      were established. A total of 53 differential protein spots were detected, and 35
      differential proteins were successfully identified. Of the identified proteins,
      32 proteins were up-regulated, and 3 proteins were down-regulated in HL-60 cells
      after 5-aza-2-dC treatment. CONCLUSION: Thirty-five differential proteins may be
      associated with methylation in HL-60 cell line, which provides the important
      clues for epigenetic study of leukemia.

PMID- 20693704
TI  - Interaction between nuclear localization signal-retinoic acid receptor alpha and
      Ubiquilin 1.
AB  - OBJECTIVE: To identify the interaction between nuclear localization signal
      retinoic acid receptor alpha (NLS-RARalpha) and Ubiquilin 1(UBQLN1). METHODS: The
      recombination expression plasmids pGBKT7-NLS-RAR and pACT2-UBQLN1, which
      expressed bait-protein NLS-RARalpha and target protein UBQLN1 respectively, were
      cotransformated into yeast AH109. The interaction of the expression plasmids in
      the living cells was investigated by yeast two-hybrid assay. HA-tagged fusion
      protein (pCMV-HA-NLS-RARalpha) expression vector and Myc-tagged fusion protein
      (pCMV-Myc-JTV1) expression vector were constructed, identified, and cotransfected
      respectively into human embryo kidney 293 cells(HEK293). The interaction was
      detected by co-immunoprecipitation. RESULTS: Blue clones were found on yeast
      AH109 plate cotransformated with pGBKT7-NLS-RARalpha and pACT2-UBQLN1. Double
      restriction enzyme digestion showed that pCMV-HA-NLS-RARalpha and pCMV-Myc-JTV1
      were successfully constructed. Then HA-NLS-RAR protein was immunoprecipitated by
      anti-HA polyclonal antibody and the expression of Myc-UBQLN1 was tested by
      Western blot with anti-Myc monoclonal antibody from immunoprecipitated complex.
      CONCLUSION: The interaction between NLS-RARalpha and UBQLN1 can be verified by
      yeast two-hybrid assay and co-immunoprecipitation.

PMID- 20693705
TI  - Clinical analysis of critically ill patients with H1N1 influenza.
AB  - OBJECTIVE: To determine the clinical characteristic, main treatment, and
      prognosis for the sake of more effective treatments for critically ill patients
      with H1N1 influenza. METHODS: Eight critically ill patients with H1N1 influenza
      in intensive care unit were retrospectively studied, including clinical
      characteristics, indexex of correlation, and prognosis. RESULTS: The acute
      physiology and chronic health evaluation II score was 19.0+/-7.8. Five patients
      died, 4 of whom were caused by respiratory failure. The number of platelets in
      dead patient was lower than that in healing and improved
      ones(chi2=8.000,P<0.05).All the 4 patients treated with glucocorticoid died, 5
      out of the 6 patients received invasive mechanical ventilation rather than
      noninvasive mechanical ventilation, and 3 of them who complicated barotraumas in
      the lung died at last. CONCLUSION: Critically ill patients with H1N1 influenza
      have high mortality. Respiratory failure is the main cause of death. Critically
      ill patients with H1N1 influenza should not be treated with glucocorticoid.
      Patients who need mechanical ventilation should be treated with invasive
      mechanical ventilation with low tidal volume and low positive end-expiratory
      pressure.

PMID- 20693706
TI  - Finite element analysis for interfacial stress and fatigue behaviors of
      biomimetic titanium implant under static and dynamic loading conditions.
AB  - OBJECTIVE: To investigate the stress distributions on implant-bone interface and
      fatigue behaviors of biomimetic titanium implant under static and dynamic loading
      conditions to provide theoretical basis for a new implant which may effectively
      transfer the stress to surrounding bones. METHODS: A 3-D finite element model of
      a posterior mandible segment with an implant bone was constructed by a CAD (Pro/E
      Widefire 2.0) software. Two different implant models (a dense implant No.1 and a
      biomimetic implant No.2) were designed. The stress distributions on bone-implant
      interface under dynamic and static loading conditions were analyzed by Ansys
      Workbench 10.0 software, as well as the fatigue behavior of the biomimetic
      implant. RESULTS: The cervical cortical bones in the 2 implants were all high
      stress region under the same loading condition. The maximum von Mises stress on
      the interface and high-stress region in the cancellous bone region, and the
      maximum stress in the root region of the biomimetic implant were lower than those
      of the dense implant. The stress on the implant-bone interface decreased from the
      top to the bottom. The stress in the cervical cortical bone under the dynamic
      loading was 17.15% higher than that of the static loading. There was no
      significant difference in maximum stress at the cortical bone region between the
      dynamic and static loading conditions. The maximum stress of the dense implant in
      the cancellous bone region was 75.97% higher and that in the root region was
      22.46% higher than that of the biomimetic implant. The maximum stress on the
      implant-bone interface was far less than the yield strength of pure titanium. The
      stress distribution in the cortical region of the biomimetic implant was 7.85%
      higher than that of the dense implant, and the maximum stress in the cortical
      bone was smaller than the yield stress of cortical bone. Within the dynamic
      loading of 50-300 N, the safety coefficient was all higher than 10, and with the
      increase of loading pressure, interface stress in the cancellous region increased
      linearly. Under the loading of 300 N in the axial and 25 N in the lingual 45:,
      the maximum stress was 11.38 MPa. CONCLUSION: Biomimetic style implant can
      effectively transfer the implant-bone interface stress to surrounding bones in
      the cancellous bone and root region, and the structure with the improved design
      is safe under normal loading pressure.

PMID- 20693707
TI  - Vitrification technology in whole embryo freezing.
AB  - OBJECTIVE: To investigate the clinical outcome of patients who underwent whole
      embryo vitrification freezing and thawed frozen embryo transplantation, and to
      compare it with the patients at the same period in the fresh cycle to explore the
      value of vitrification technology in the whole embryo freezing combined with
      recovery transplantation. METHODS: The whole embryo freezing group included 40
      untransplanted cases of in-vitro fertilization (IVF), while another 300 patients
      in the fresh cycle with in vitro fertilization and embryo transfer (IVF-ET) at
      the same period served as the fresh cycle group. The average number of
      transferred embryos, high-quality embryos, endometrial thickness, estradiol (E2)
      level, and clinical pregnancy rate were compared. RESULTS: The average number of
      transferred embryos, high-quality embryos, difference in endometrial thickness
      were not significant between the 2 groups (P>0.05); the E2 level of the fresh
      cylcle group was significantly higher than that of the whole embryo freezing
      group (P<0.05), and the clinical pregnancy rate in the fresh cylcle group was
      significantly lower than that of the whole embryo freezing group (P<0.05).
      CONCLUSION: Vitrification technology is a simple, reliable, and efficient embryo
      freezing technology. For patients who meet the requirements, whole embryo
      vitrfication freezing and thawed frozen embryo transplantation is feasible. It is
      worth for further clinical research.

PMID- 20693708
TI  - [Autobiographical memory of depressed patients].
AB  - OBJECTIVE: To explore the autobiographical memory characteristics in depressed
      patients and their influence factors. METHODS: Autobiographical memory, emotion
      and cognitive executive function of 60 depressed patients and 60 healthy controls
      were assessed with autobiographical memory test (AMT), Hamilton depression scale
      (HAMD), Beck depression inventory (BDI), Beck anxiety inventory (BAI), hospital
      anxiety and depression scale (HAD), arrow-task stroop test (ATST), Wisconsin card
      sorting test (WCST), Backward masking test (BMT) and continuous performance test
      (CPT). RESULTS: The specific memory of the depressed group was significantly less
      than that of the control group, and was negatively related with the negative
      emotion score, the time of anterograde and retrograde reading of ATST, and the
      time difference of ATST. The overgeneral memory increased and the latency to
      response of ATST was significantly longer than that of the control group. The two
      factors were positively related with the negative emotion score, the time of
      anterograde and retrograde reading of ATST, and the time difference of ATST.
      CONCLUSION: The autobiographical memory of the depressed patients is
      overgeneralized and retarded. These characteristics are related with negative
      emotion and impairment of cognitive executive function.

PMID- 20693709
TI  - [Effect of soluble epoxide hydrolase inhibitor on the function of endothelial
      progenitor cells in patients with coronary heart disease].
AB  - OBJECTIVE: To investigate the effect of soluble epoxide hydrolase inhibitor
      (sEHi) tAUCB on the function of endothelial progenitor cells (EPCs) and
      expression of vascular endothelial growth factor (VEGF) in EPCs in patients with
      coronary heart disease (CHD). METHODS: Mononuclear cells, from the peripheral
      blood of CHD patients, were isolated by ficoll density gradient centrifugation
      and cultured. After 7 days of culture in vitro, EPCs were identified by double
      staining and flow cytometry. EPCs were then stimulated by 0, 10(-6), 10(-5), and
      10(-4) mol/L of tAUCB for 24 h. Migration assay was performed in transwell
      chamber and tube formation assay was performed by Matrigel-Matrix in vitro model.
      The expression of VEGF in EPCs was measured by Western blot. EPCs from age and
      gender matched healthy subjects were also cultured as controls. RESULTS: The
      migration and tube formation activities of EPCs from CHD patients were obviously
      damaged compared with those from healthy controls (P<0.05). The tAUCB could dose
      dependently increase the migration and tube formation activities and increase the
      expression of VEGF in EPCs compared with those from CHD patients without
      treatment. The 10(-6) mol/L tAUCB increased those activities of EPCs and the
      expression of VEGF with statistical difference. CONCLUSION: sEHi can positively
      modulate the function of EPCs from CHD patients, suggesting the potential
      predictive significance of sEHi in the therapy of CHD.

PMID- 20693710
TI  - [Sympathetic nervous system level and ambulatory blood pressure in children with
      primary nephrotic syndrome].
AB  - OBJECTIVE: To explore the change in ambulatory blood pressure monitoring (ABPM)
      value and the sympathetic nervous system (SNS) level in children with primary
      nephrotic syndrome(PNS) and their relationship. METHODS: ABPM and casual blood
      pressure(CBP) were tested in 114 children with PNS and 12 normal children as a
      control group. The 24-h urine noradrenaline(NA), adrenaline(A) and dopamine(DA)
      content were detected through high-performance liquid chromatography with
      electrochemical luminescence and the correlation with ABP was analyzed. RESULTS:
      Among 114 children with PNS, 101 had elevated blood pressure (88.6%), 45 showed
      high incidence of masked hypertension (39.5%), and 80 non-dipper blood pressure
      (70.2%). Systolic blood pressure level and blood pressure load were greater than
      diastolic blood pressure. NA, A, and DA levels of the PNS group were
      significantly higher than those of the control group, while those of the elevated
      blood pressure group were significantly higher than those of the normal blood
      pressure group in PNS children. SNS levels were positively correlated with blood
      pressure levels and blood pressure load, and negatively correlated with night BP
      decreasing rates. CONCLUSION: Children with PNS have high incidence of
      hypertension with large proportion of masked hypertension and non-dipper blood
      pressure. Severe masked hypertension classification should be set up. In PNS
      children, SNS activity is elevated that might evaluate the blood pressure level
      and decrease blood pressure circadian rhythm.

PMID- 20693711
TI  - [Change of serum soluble CD14 level in newly diagnosed type 2 diabetes and its
      significance].
AB  - OBJECTIVE: To determine the correlation of serum soluble CD14 (sCD14) level with
      the injury of vascular endothelial cells and chronic low grade inflammation in
      newly diagnosed Type 2 diabetes (T2DM). METHODS: ELISA was used to examine serum
      sCD14 and serum soluble E-selectin (sE-selectin) level, while immunoturbidimetric
      assay was used to detect serum high sensitivity C reactive protein (hsCRP).
      RESULTS: The levels of serum sCD14, sE-selectin, and hsCRP in newly diagnosed
      T2DM group were higher than those in the euglycemic group [sCD14: (300.7+/-136.6)
      ng/mL vs. (273.3+/-86.0) ng/mL); sE-selectin: (21.3+/-7.7) ng/mL vs. (32.9+/
      11.4) ng/mL; hsCRP: (1.45+/-1.21) mg/L vs. (2.37+/-1.45)mg/L], and there was a
      significant difference in the latter two parameters between the 2 groups(P<0.01).
      In the patients with newly diagnosed T2DM, after matching blood pressure, blood
      sugar, and blood lipid, the levels of serum sCD14, sE-selectin, and hsCRP in the
      obese group were higher than those in the non-obese group. There was no
      significant difference in the former 2 parameters between the 2 groups. The serum
      sE-selectin was correlated with fasting blood sugar (r=0.369, P<0.001), 2-hour
      postprandial blood sugar (r=0.421, P<0.001), glycosylated hemoglobin (r=0.291,
      P=0.005), sCD14(r=0.312, P=0.002), and homeostasis model assessment-insulin
      resistance(r=0.247, P=0.018) in the newly diagnosed T2DM group. Stepwise
      regression ana-lysis showed that the serum sCD14 was one of the chief influencing
      factors on serum sE-selectin. CONCLUSION: Serum sCD14 levels tend to increase in
      newly diagnosed T2DM patients, especially in the obese diabetic patients, which
      is one of the chief influencing factors to induce the injury of vascular
      endothelial cells. The innate immunity mediated by Toll-like receptor 4 may take
      part in the injury of vascular endothelial cells in newly diagnosed T2DM
      patients.

PMID- 20693712
TI  - [Urodynamic studies on benign prostatic hyperplasia combined with diabetes
      mellitus].
AB  - OBJECTIVE: To evaluate urinary dynamics in the diagnosis, differential diagnosis,
      disease grades, complications, prognosis, and curative effect on benign prostatic
      hyperplasia (BPH) patients accompanied with diabetic mellitus (DM), and to
      investigate the clinical significance of urodynamic studies. METHODS: A total of
      106 BPH patients with lower urinary tract symptoms were studied, aged 53
      92(63.21+/-7.18) years. The mean duration of voiding symptoms was 3-12 years.
      These patients were divided into 2 groups: Group A consisted of 59 BPH patients
      while Group B consisted of 47 BPH patients combined with DM. Both groups were
      evaluated the international prostate symptom score(IPSS), urine flow rate, and
      residual urine volume. All patients underwent urodynamic examination. Correlation
      analysis was conducted to determine the correlation among the patients. The
      urodynamic results in different groups were compared. RESULTS: The IPSS in Group
      A was higher than Group B, while the Qmax was lower than Group B. The
      unsatisfactory results of Group A was higher than Group B. There was significant
      difference between the 2 groups (P<0.05). There was no significant difference in
      residual urine volume between the 2 groups (P>0. 05). There was significant
      difference between the 2 groups in detrusor instability of the bladder, low
      compliance bladder, and damaged detrusor function (P<0.05). CONCLUSION: The
      influence of DM on the function of the bladder in BPH patients is significant.
      Urodynamics can provide objective basis for the selection of therapeutic methods,
      and forecast the postoperative effect. It has an important reference value in BPH
      patients accompanied with DM.

PMID- 20693713
TI  - [Inhibitory effect of DADS on transplantation tumor from hepatic carcinoma HePG2
      cells in nude mice].
AB  - OBJECTIVE: To investigate the inhibitory effect of diallyl disulfide (DADS) on
      transplantation tumor from hepatic carcinoma HePG2 cells in nude mice and its
      mechanism. METHODS: Hepatic carcinoma HePG2 cell transplantation tumor model in
      nude mice was established and the effect of DADS on the growth of transplantation
      tumor was observed. Cell apoptosis and proliferation associated protein
      expressions were assayed by immunohistochemical method and Western blot. Cell
      apoptosis was assayed by TUNEL. RESULTS: DADS could inhibit HePG2 cell
      transplantation tumor growth in nude mice. TUNEL showed that DADS enhanced the
      cell apoptosis and apoptosis-promoting protein caspase-3 expression, decreased
      apoptosis-inhibiting protein bcl-2 expression, and also inhibited proliferation
      associated protein PCNA expression. CONCLUSION: DADS may inhibit HePG2 cell
      transplantation tumor growth in nude mice and involve in the inhibition of cell
      proliferation and enhancement of cell apoptosis.

PMID- 20693714
TI  - [RNA interference of HDAC7 expression in hepatocellular carcinoma].
AB  - OBJECTIVE: To investigate the role of histone deacetylase 7 (HDAC7) in the
      occurrence and development of hepatocellular carcinoma. METHODS: HepG2 cells and
      human microvascular endothelial cells (HMEC-1) were divided into 3 groups after
      transfection pSUPER-HDAC7 retroviral interference plasmid: a pSUPER(HDAC7RNAi+)
      group, a pSUPER(HDAC7RNAi-) group, and a pSUPER group as the control group. The
      expression of HDAC7, p21, cyclin E, matrix metalloproteinases 10 (MMP10), and
      hypoxiainducible factor-1alpha (HIF-1alpha) were detected by Western blot. The
      expression of HDAC7 in cell lines was determined by 3-(4,5-Dimethylthiazol-2-yl)
      2,5-diphenyltetrazolium bromide (MTT) and flow cytometry, the nude mice modle,
      and vascular endothelial cells 2-dimensional tubulogenesis in vitro and in vivo.
      RESULTS: Compared with the control group and the pSUPER(HDAC7RNAi-) group, the
      expression of HDAC7 was downregulated, the rate of cell growth inhibition and
      apoptosis in the pSUPER(HDAC7RNAi+) group increased more significantly; the
      expression of p21 and HIF-1alpha was increased significantly, while the
      expression of cyclin E and MMP10 in the pSUPER(HDAC7RNAi+) group was
      downregulated (P<0.05). CONCLUSION: The expression of HDAC7 protein plays an
      important role in the apoptosis and vascular tubulogenesis of hepatocellular
      carcinoma by the upregulation of p21 and HIF-1alpha and the downregulation of
      cyclin E and MMP10.

PMID- 20693715
TI  - [Effect of human recombinant PDCD5 protein on cell apoptosis of multiple myeloma
      KM3 cells induced by dexamethasone and its mechanism].
AB  - OBJECTIVE: To observe the effect of programmed cell death 5 (PDCD5) protein on
      the apoptosis of multiple myeloma KM3 cells induced by dexamethasone and to
      understand its mechanism. METHODS: The human recombinant PDCD5 (rhPDCD5) protein
      was added (alone of different concentrations or associated with dexamethasone)
      into KM3 cells. Cultured together for certain time, the cells were collected for
      the following experiments: (1)The effect of rhPDCD5 protein and dexamethasone on
      the apoptotic rate of KM3 cells was determined by flowcytometry (FCM) analysis
      after the cells were stained by Annexin V-FITC & PI (propidium iodide).
      (2)Caspase-3 activity of KM3 cells was evaluated by Western blot. (3)The
      expression of survivin protein in KM3 cells was detected by immunocytochemistry.
      RESULTS: The apoptotic rate of KM3 cells and the activity of caspase-3 increased
      significantly, and that treated with rhPDCD5 protein and dexamethasone was higher
      than that treated with rhPDCD5 protein only. The expression of survivin protein
      in the rhPDCD5 with dexemethas group was down-regulated, and with the
      concentration of rhPDCD5 and dexamethasone increasing, the changes was more
      obviously. CONCLUSION: PDCD5 protein can induce the apoptosis of KM3 cells, and
      accelerate the apoptosis of KM3 cells induced by dexamethasone. PDCD5 protein may
      reduce the expression of survivin protein and increase activation of caspase-3 to
      play its role in promoting apoptosis.

PMID- 20693716
TI  - [Effect of different concentrations of vitamin C on proliferation and apoptosis
      of C2C12 myoblasts].
AB  - OBJECTIVE: To explore the effect of different concentrations of vitamin C on
      proliferation and apoptosis of C(2)C(12) myoblasts. METHODS: C(2)C(12) cells
      cultured in vitro were collected by trypsinization to form monoplast suspension,
      and then centrifuged to float again. The cellular numbers were counted and the
      cell suspension density adjusted, and the cells were inoculated into 96-shadow
      mask according to 200 MUL per hollow. All cells were cultured in the normal way.
      While cell fusion ratio arrived 80% and cells did not differentiate, cells were
      divided into 6 groups: a negative control group (pure DMEM-F12 medium), an
      H(2)O(2) group (DMEM-F12 medium containing 500 MUmol/L H(2)O(2)) and vitamin C
      group 1 to 4(DMEM-F12 medium containing 500 MUmol/L H(2)O(2) and 10, 20, 60, and
      100 mg/L vitamin C, respectively). After each group was treated for 0, 6, 24, 36,
      48,and 72 h, respectively, MTT was used to detect C(2)C(12) cell proliferation in
      each group. Annexin V-PI double staining was applied to detect C(2)C(12) cell
      apoptosis in each group after treatment for 36 h. RESULTS: After the cells were
      treated for 36 h and 72 h, the absorbance of vitamin C group 1 to 4 were higher
      than that of H(2)O(2) group (P<0.001). The absorbance of vitamin C group 4 was
      the highest among all the groups, significantly higher than that of the negative
      control group when the cells were treated for 36 h (P<0.05). When the cells were
      treated for 36 h, the C(2)C(12) cells apoptosis rate of vitamin C group 2 to 4
      was lower than that of H(2)O(2) group; The C(2)C(12) cells apoptosis rate of
      vitamin C group 2 and 3 was higher than that of the negative control group, while
      the C(2)C(12) cells apoptosis rate of vitamin C group 4 was significantly lower
      than that of the negative control group (P=0.009). CONCLUSION: Vitamin C can
      efficiently inhibit the apoptosis of C(2)C(12) myoblasts induced by H(2)O(2), and
      after 36 h intervention, high concentration vitamin C may promote C(2)C(12) the
      proliferation of myoblasts.

PMID- 20693717
TI  - [Human normal sperm morphology rate and in vitro fertilization outcome].
AB  - OBJECTIVE: To determine the effect of sperm morphology on fertilization rate,
      cleavage rate,and clinical pregnancy rate, which may help to choose a best
      protocol before assisted reproductive technology (ART). METHODS: We a
      retrospectively surveyed semen data of 1369 ART patients from January to December
      2008 in our hospital. We divided sperms from 751 patients into 4 groups based on
      the sperm morphology rate: <=5.0% (normal), 5.1%-10.0%, 10.1%-15.0%, and >15.0%.
      In vitro fertilization (IVF) was used for 490 patients or intracytoplasmic sperm
      injection (ICSI) for 261. We also divided sperms from 618 donors into 4 groups
      based on the sperm morphology rate: 14.0%-17.0%(normal), 17.1%-19.0%, 19.1%
      23.0%, and >23.0%. Only IVF was used for these donors. The fertilization rate,
      cleavage rate, and clinical pregnancy rate among each group were analyzed and
      discussed. RESULTS: During the IVF(patients or donors) cycle, there was a
      significant difference among the 4 groups in the fertilization rate and clinical
      pregnancy rate (P<0.05), but there was no difference in the cleavage rate
      (P>0.05). In the ICSI cycle, there was no significant difference among the 4
      groups in the fertilization rate, clinical pregnancy rate, and cleavage rate
      (P>0.05). CONCLUSION: Sperm morphology affects the outcome of IVF. There is no
      significant influence of sperm morphology on the outcome of ICSI. ICSI is an
      optimal alternative for patients with abnormal morphological sperms in ART.

PMID- 20693718
TI  - [A survey on AIDS knowledge rate and sexual behavior among men who have sex with
      men population at sexually transmitted disease clinic].
AB  - OBJECTIVE: To survey on men who have sex with men (MSM) population's sexual
      behaviors, condom-service condition, HIV related knowledge and other issues among
      MSM population at sexually transmitted disease (STD) clinics to understand the
      characteristics of behaviors and offer suggestions for effective health education
      and behavior intervention. METHODS: From January to December, 2009, we used
      anonymous questionnaires which involved in their mastery of demographic
      characteristics, sexual behavior, condom-service condition, HIV related
      knowledge, and so one, to investigate 200 MSM at 3 STD clinics of comprehensive
      hospital. RESULTS: The average age of informant was (26.7+/- 8.9) years and 121
      individuals (62.6%) had confirmed with STD in recent one year. In the recent 6
      months, the average number of homosexual partners was 9.2+/- 4.8 and 102 (52.8%)
      had heterosexual partners. In the sexual intercourse with homosexual, 123
      individuals had anal intercourse (63.7 %) and 117 had oral intercourse (60.6%).
      In the sexual intercourse with heterosexual, 92 (90.2%) individuals had vaginal
      intercourse, 37 (36.2%) had anal intercourse, and 59 (57.8%) had oral sex
      behavior.There were a statistical difference between heterosexual and homosexual
      sex behaviors (P<0.01). The condom-using frequency had statistic difference in
      different sexual behaviors(chi2=188.396, P<0.001). There was no linear
      correlation between HIV related knowledge and condom-using condition in sexual
      behaviors except the heterosexual anal intercourse. CONCLUSION: High AIDS
      knowledge mastery rate is found in our survey. The respondents get HIV/AIDS
      knowledge through various ways actively. There is no obvious relation between the
      mastery of HIV related knowledge and condom-using frequency. The ratio of non
      protected sexual behaviors is high in heterosexuals. How to adopt effective
      methods for behavior intervention to MSM at STD clinic needs to be further
      studied.

PMID- 20693719
TI  - [Effect of genistin on proliferative vitreoretinopathy].
AB  - OBJECTIVE: To examine the effect of genistin on traumatic proliferative
      vitreoretinopathy (PVR) in rabbits. METHODS: Traumatic PVR was induced in
      pigmented rabbits by intravitreal injection of platelet rich plasma. The eyes
      then received an intravitreal injection of dimethyl sulfoxide (0.1 mL), 2 or 40
      MUg genistin (0.1 mL), and 1 mg fluorouracil(0.1 mL), respectively to form 4
      groups. The eyes were examined ophthalmoscopically on distinct days after the
      surgery and the stage of PVR was evaluated. The model eyes and normal eyes in the
      40 MUg genistin group carried ERG test on the 28th day. All model eyes in the 4
      groups were observed by light microscope on the 28th day. RESULTS: In the control
      eyes, the retina was detached after 10 d, the PVR had progressed to higher stages
      with time. In the eyes injected 40 MUg genistin or fluorouracil, the PVR also
      developed; however, the severity of PVR was lower than that in the control eyes.
      PVR was significantly inhibited in the 40 MUg genistin group compared with the
      control eyes after 14 d (P<0.05). Histological examination of the genistin
      treated eyes disclosed no morphological changes, and ERG analysis revealed no
      significant functional changes. CONCLUSION: Intravitreal injection of genistin is
      safe and effective in reducing traumatic PVR in clinical treatment.

PMID- 20693720
TI  - [Effect of length-width ratio on partial necrosis in distally based sural
      neurofasciocutaneous flap: 157 cases].
AB  - OBJECTIVE: To explore the effect of length-width ratio (LWR)on partial necrosis
      in distally based sural neurofasciocutaneous flap. METHODS: Clinical data and
      operative pictures of 157 distally based sural neurofasciocutaneous flaps were
      reviewed and analysed. LWR of the flaps ranged from 2.83:1 to 7.14:1. Based on
      the LWR of the flaps, the flaps were divided into 5 groups: Group A(LWR<=3:1),
      Group B(3:1<LWR<4:1), Group C(4:1<=LWR<5:1), Group D(5:1<=LWR<6:1) and Group E
      (LWR>=6:1). The flaps were harvested by antegrade-retrograde combined method.
      RESULTS: Of the 157 flaps, 125 survived uneventfully, 8 had distal epidermical
      necrosis, wound dehiscence occurred in 6 flaps, 18 flaps(11.5%) had distal
      partial necrosis. Partial necrosis occurred in none of the 6 flaps in Group
      A(0%), 4 of 26 flaps in Group B(12.5%), 2 of 56 flaps in Group C (3.6%), 8 of 50
      flaps in Group D (16.0%), and 4 of 19 flaps in Group E(21.5%). There were no
      statistical differences in partial necrosis ratio between Group A and B, Group B
      and C, Group D and E(P>0.05). Partial necrosis ratio was higher in Group D than
      that in Group C(P<0.05). It was lower in the LWR<5:1 group (Group A+Group B+Group
      C) (6.8%, 6/88) than that in the LWR>=5:1 group (Group D+Group E) (17.4%, 12/69)
      (P<0.05). CONCLUSION: When LWR of the flap is less than 5:1, probability of
      partial necrosis occurring in distally based sural neurofasciocutaneous flaps is
      low, and the flap can survive more reliably. The maximum LWR of the surrival
      flaps can reach 6-7:1.

PMID- 20693721
TI  - [Diffusion-weighted magnetic resonance imaging for acute trauma of the spine
      cord].
AB  - OBJECTIVE: To determine the clinical value of diffusion-weighted magnetic
      resonance imaging (DWI) for acute trauma of the spinal cord. METHODS: Sixteen
      patients with acute trauma of the spinal cord were examined with routine magnetic
      resonance imaging (MRI) and ssh-EPI-DWI, on a 1.5-tesla MR system within 72 h
      trauma. RESULTS: All the 16 patients were examined by MRI and ssh-EPI-DWI: 6
      patients were negative and 10 were positive in MRI, which showed local lesions
      with significant abnormality. Positive cases were classified into 2 categories
      depending on different degrees of tissue injury and characteristics of DWI. (1)
      Edema-type: 7 presented DWI high signals with different degrees in local lesions.
      (2) Mixed-type: 3 showed DWI heterogeneous high signals due to hemorrhage and
      edema in the lesions. There was significant difference in ADC values between the
      lesions and normal parts (t=-7.719, P<0. 01). CONCLUSION: ssh-EPI-DWI of the
      spinal cord may provide satisfactory images and is a useful method for
      visualizing the injury in the superearly stage, helpful to determine the
      integrity and compression degree of the spinal cord.

PMID- 20693722
TI  - [Effect of qinghuobaiduyin on the expression of high mobility group box
      chromosomal protein 1 in macrophage].
AB  - OBJECTIVE: To observe the expression of high mobility group box chromosomal
      protein 1(HMGB1) in RAW264.7 macrophages after interfering with burning serum and
      qinghuobaidu-yin (QHBDY), and to find out the endogenous protection mechanism of
      QHBDY resisting inflammation reaction. METHODS: RT-PCR was used to detect the
      expression of HMGB1 in RAW264.7 macrophages after interfering RAW264.7
      macrophages with normal SD rat serum, burning SD rat serum, and QHBDY feeding SD
      rat serum. RESULTS: Small quantity of HMGB1 mRNA was expressed in RAW264.7. The
      expression of HMGB1 mRNA fluctuated around the standard level after interfering
      with normal serum of SD rats. The expression of HMGB1 mRNA rose at 3 h, and then
      decreased to the standard level; at 18 h, it rose rapidly; at 36 h, it reached
      the peak; and at 48 h, it remained at the high level after interfering with
      burning serum. The expression of HMGB1 mRNA increased at 3 h, and then decreased
      to the standard level. At 24 h, it started to rise after interfering with herb
      serum, and was lower than that of; the burning serum group (P<0.05). CONCLUSION:
      Burning serum can increase the expression of HMGB1 mRNA in RAW264.7. QHBDY can
      decrease the high expression of HMGB1 mRNA in RAW264.7 caused by burning serum.

PMID- 20693723
TI  - An auspicious development: ADA sesquicentennial.

PMID- 20693724
TI  - A childhood obesity program in federally qualified community health centers.

PMID- 20693725
TI  - Using a community partnered participatory research approach to implement a
      randomized controlled trial: planning community partners in care.
AB  - SUMMARY: Quality improvement (QI) for depression in primary care can reduce
      disparities in outcomes. We describe how community-partnered participatory
      research was used to design Community Partners in Care, a randomized trial of
      community engagement to activate a multiple-agency network versus support for
      individual agencies to implement depression QI in underserved communities.

PMID- 20693726
TI  - Levels and correlates of patient activation in health center settings: building
      strategies for improving health outcomes.
AB  - Patient activation refers to people's ability to engage in self-management of
      their health and health care. We assessed the performance of the Patient
      Activation Measure (PAM) for patients attending three inner-city health centers
      and compared resultant scores with those of the general U.S. adult population. We
      approached 801 patients and 527 (65.8%) participated; the majority were Latino(a)
      or African American/Black. No differences in activation were seen according to
      age. Males and more educated patients were more activated (p<.05) and patients
      with better self-rated health and adequate health literacy were more activated
      than their counterparts (p<.001). Patterns of scores resembled those of the U.S.
      general population for educational attainment and self-rated health but not for
      gender and age. Compared with the general population, more patients were
      characterized as level 1 (least activated). Developing strategies that enhance
      patient activation is critical to improving health outcomes, particularly in less
      advantaged populations.

PMID- 20693727
TI  - Protecting citizen-children safeguards our common future.
AB  - For every two adult undocumented immigrants that are deported from the U.S., one
      citizen-child is affected. With roughly 1.3 million adults deported in the past
      decade, the number of citizen-children is staggering. Deportation forces parents
      to make crucial decisions about their U.S.-born children: to take them or leave
      them behind. Our deportation policies and practices fall hardest on citizen
      children in mixed-status families. In this commentary, I review the conditions
      facing citizen-children, and consider the consequences to the children and to the
      U.S. To remedy the effects of deportation policies and practices, federal
      immigration enforcement must follow sound child welfare models. Solid health and
      educational research helps immigration courts in decision-making by documenting
      the effects of parental deportation on citizen-children. Promoting legislation
      such as the Child-Citizen Protection and The Dream Act insures the principled and
      humane treatment of citizen-children. International treaties and programs that
      protect citizen-children will also safeguard our nation's future.

PMID- 20693728
TI  - Strength and courage: the development of a native American cancer survivor
      archive.
AB  - SUMMARY: This report describes the first Native American cancer survivor archive
      and lessons learned from its development. Unusual not only in its holdings, this
      archive project is distinct as it is led by researchers and community health
      advocates without professional archival development training.

PMID- 20693729
TI  - Body image in Hispanic/Latino vs. European American adolescents: implications for
      treatment and prevention of obesity in underserved populations.
AB  - Hispanic/Latino (H/L) vs. European American (EA) perceptions of current and ideal
      body image as well as body dissatisfaction were examined in 416 adolescents aged
      12-15 years. Gender, culture, and body mass index (BMI) were hypothesized to
      affect measures of self-perceived body image and dissatisfaction differentially.
      Participants completed a computerized survey with gender-specific versions of
      applicable test items. Overall, body dissatisfaction (BD) was higher among EAs
      vs. H/Ls, females vs. males, and unhealthy BMI vs. healthy BMI (p<.01). A gender
      x ethnicity interaction trend was also noted (p>.06), in which BD was highest
      among EA females, followed by H/L females, EA males, and H/L males. Results
      suggest that gender and cultural differences in body image among adolescents are
      significant. This study is an important step toward clarifying the nature of
      weight-related health risks facing the understudied population of Hispanic/Latino
      teens.

PMID- 20693730
TI  - Factors associated with pap testing among Hmong women.
AB  - This paper reports the baseline data on the proportion of Hmong women (n=402),
      ages 18-65, in Sacramento, California who reported that they had a Pap test for
      the early detection of cervical cancer. We assessed the association between
      sociodemographic characteristics and Pap test receipt using chi-squared and
      multiple logistic regression analyses. Only 74% had ever had a Pap test, with 61%
      tested in the previous three years, compared with 91% and 86%, respectively, of
      California women overall. Women were more likely to have had a recent Pap test if
      they were age 21-30 (OR=3.0 vs. age 51-65, 95% CI 1.4-6.7) or 31-40 (OR=3.0, 95%
      CI 1.4-6.4), and less likely if they were single (OR=0.4 vs. married/partnered,
      95% CI 0.2-1.0) or born in the U.S. (OR=0.3 vs. <10 years in U.S., 95% CI 0.1
      0.8).

PMID- 20693731
TI  - Factors influencing the receipt of hepatitis B vaccination and screenings in
      Vietnamese Americans.
AB  - This study examined factors affecting the receipt of both hepatitis B vaccination
      and screening in the Vietnamese American community of Philadelphia. Hepatitis B
      is endemic in Southeast Asia; individuals emigrating from endemic areas are at a
      particularly high risk of hepatitis B infection, resulting in a higher prevalence
      of liver cancer in the population. Participants recruited at Vietnamese community
      events in Philadelphia completed a self-administered written questionnaire. In a
      sample of 207 participants (93% foreign-born), over one half reported that they
      had not received either a screening or vaccination for hepatitis B in their
      lifetime. The number one predictor of receiving either service was that the
      participant was aware of the cancer risk posed by hepatitis B. This association
      remained strong even when controlling for socio-demographic factors. Based on
      this finding, future interventions targeting this population should include
      messages on the cancer risk associated with hepatitis B.

PMID- 20693732
TI  - Health care-seeking among Latino immigrants: blocked access, use of traditional
      medicine, and the role of religion.
AB  - Barriers to health care and use of cultural alternatives are studied from open
      ended interviews of 96 Latino immigrants, 12 hometown association leaders, and
      five pastors and health outreach workers. Frequently mentioned barriers to
      approaching hospitals and clinics included problems in communication,
      establishing financial eligibility, and extremely long waits for service. We
      found frequent use of cultural alternatives, such as herbal medications,
      obtaining care from Mexican doctors, and some use of traditional healers. The
      role of religiosity is studied: prayer is viewed as fundamental to health, but
      the church is not perceived as an aid in physical health-seeking. Health care for
      Latino immigrants often involves a blend of mainstream and traditional medicine;
      the study discusses examples of respondents who navigate between the two systems
      within the interplay of culture and structure.

PMID- 20693734
TI  - Policy, autonomy, and physician satisfaction.
AB  - It is important to understand how policy influences physician satisfaction, which
      in turn affects access to and quality of care. Two Mississippi policy crises in
      the past decade indirectly jeopardized its primary health care supply. During a
      volatile malpractice climate in 2002, physician groups claimed physicians would
      retire or relocate or quit medicine entirely. The second crisis in 2005
      temporarily shut down Medicaid reimbursement. Both crises had the capacity to
      undermine physician satisfaction, a predictor of physician retention. We used
      data from two cross-sectional Mississippi physician surveys to test how
      malpractice experiences and Medicaid reimbursement influenced physician
      satisfaction. The Medicaid shutdown had no measurable effect on physician
      satisfaction, while the immediate effects of a litigious malpractice climate
      dampened physician satisfaction. However, the data indicate that the effects of
      malpractice experiences may be quite short-lived.

PMID- 20693733
TI  - More than Tuskegee: understanding mistrust about research participation.
AB  - This paper describes results of a qualitative study that explored barriers to
      research participation among African American adults. A purposive sampling
      strategy was used to identify African American adults with and without previous
      research experience. A total of 11 focus groups were conducted. Groups ranged in
      size from 4-10 participants (N=70). Mistrust of the health care system emerged as
      a primary barrier to participation in medical research among participants in our
      study. Mistrust stems from historical events including the Tuskegee syphilis
      study and is reinforced by health system issues and discriminatory events that
      continue to this day. Mistrust was an important barrier expressed across all
      groups regardless of prior research participation or socioeconomic status. This
      study illustrates the multifaceted nature of mistrust, and suggests that mistrust
      remains an important barrier to research participation. Researchers should
      incorporate strategies to reduce mistrust and thereby increase participation
      among African Americans.

PMID- 20693735
TI  - Racial/Ethnic disparities in socioeconomic status, diagnosis, treatment and
      survival among medicare-insured men and women with head and neck cancer.
AB  - To determine whether racial disparities persist in Medicare-insured elderly
      patients with head and neck cancer, we studied 7,480 patients diagnosed with head
      and neck cancer at age 65 or older in 1991-2002, identified from tumor registries
      maintained by the 16 areas participating in the Surveillance, Epidemiology and
      End Results program. Patients receiving cancer-directed surgery had significantly
      lower risks of both all-cause and disease-specific mortality than others; those
      with lower socioeconomic status were more likely to die of all causes than
      patients with higher socioeconomic status. African Americans had a marginally
      higher risk of all-cause mortality (hazard ratio = 1.19, 95% CI: 1.07-1.33), but
      had no significantly different risk of disease-specific mortality compared with
      Whites (1.09, 0.91-1.30). In conclusion, the risk of mortality was not
      significantly different among African Americans and Hispanics compared with
      Whites in specific tumor sites of head and neck cancer except a marginally
      elevated risk of all-cause mortality in African Americans with oral cavity tumor.

PMID- 20693736
TI  - Health disparities in rural areas: the interaction of race, socioeconomic status,
      and geography.
AB  - The purpose of this study was to explore factors that may help explain the
      mortality differences between African Americans and Whites. This study was a
      retrospective analysis of data from Tennessee's 95 counties. Standardized
      mortality ratios (SMRs) for African Americans were determined based on White, all
      cause, age-specific mortality rates, and served as the dependent variable.
      Potential explanatory variables included measures of demography, socioeconomic
      status, and social environment. Bivariate and multivariate analyses showed a
      significant association between SMR and population density (t=2.18, p=.037) among
      36 counties, with more than 20 African American deaths per year, and between SMR
      and the proportion of the population that is African American (t=2.23, p=.033) in
      an analysis that included all 95 counties. Mortality differences based on
      demographic characteristics, rather than on the usual social determinants of
      health, raise further questions about the root causes of health inequities.

PMID- 20693737
TI  - African American's awareness of disparities in infant mortality rates and sudden
      infant death syndrome risks.
AB  - African American infant mortality rates (IMR) in San Francisco have remained 2.5
      to three times those of Whites for over 20 years. METHODS: A 69-item telephone
      survey of African American residents in four neighborhoods with the most African
      American births assessed awareness of IMR disparities, associated risks, and
      social capital. RESULTS: Of the 804 respondents, 57% were not aware of the IMR
      disparity. Higher levels of awareness occurred in those volunteering (OR 1.5, CI
      1.1-2.0), participating in efforts to benefit the African American community (OR
      1.8, CI 1.3-2.4), sensing that they belonged in their neighborhood (OR 1.7, CI
      1.2-2.3), and being aware of a local African American-led initiative to improve
      infant health (OR 2.3, CI 1.7-3.9). Lack of awareness can be a barrier to a
      population's engagement in improving its overall health. CONCLUSION: Lack of
      awareness of IMR disparities and risk factors exists in the San Francisco African
      American population and is related to less social capital. Improving awareness is
      a prerequisite for implementing community level interventions.

PMID- 20693738
TI  - Presence of medical schools may contribute to reducing breast cancer mortality
      and disparities.
AB  - Understanding differences among counties more or less successful in addressing
      breast cancer (BC) mortality disparities is important. Medical resources may be
      more available in counties with BC mortality rates (BCMR) low and similar for
      White and Black women. Based on Black and White BCMR we classified selected
      counties in four types from failing (high BCMR for both groups of women) to
      successful (low BCMR for both). Medical resource data were from Area Resource
      Files. In multivariate analyses, number of physicians or hospitals, HMO
      penetration, and proportion of hospitals with mammography centers did not predict
      county type. The proportion of hospitals with medical schools predicted counties
      being with Black:White disparities vs. with reverse disparities (OR 0.96, CI 0.94
      0.99), or being successful vs. failing (OR 1.03, CI 1.00-1.06) or vs. with
      disparities (OR 1.04, CI 1.01-1.07). Medical resources did not explain county
      type differences, but type of care available may be important.

PMID- 20693739
TI  - HIV testing and treatment with correctional populations: people, not prisoners.
AB  - Institutional policies, practices, and norms can impede the delivery of ethical
      standard-of-care treatment for people with HIV in correctional settings. In this
      commentary, we focus on the fundamental issues that must be addressed to create
      an ethical environment in which best medical practices can be implemented when
      working with correctional populations. Thus, we consider ethical issues related
      to access to services, patient privacy, confidentiality, informed consent for
      testing and treatment, and issues related to the provision of services in an
      institutional setting in which maintenance of security is the primary mission.
      Medical providers must understand and navigate the dehumanization inherent in
      most correctional settings, competing life demands for incarcerated individuals,
      power dynamics within the correctional system, and the needs of family and
      significant others who remain in the community.

PMID- 20693740
TI  - Microfinance: a general overview and implications for impoverished individuals
      living with HIV/AIDS.
AB  - Microfinance among people living with HIV/AIDS (PLWHA) faces some opposition and
      remains understudied. This literature review examines microfinance's evolution
      and impact on a variety of social and health indicators and its emerging
      implementation as a primary prevention tool for HIV and economic intervention for
      PLWHA. There is an abundance of literature supporting the apparent utility of
      microfinance. However, our understanding of the subject remains clouded by the
      heterogeneity and methodological limitations of existing impact studies, and
      access limitations to microfinance curbs our understanding of microfinance for
      this population. Existing literature suggests PLWHA could attain economic
      stability from microfinance and achieve successful repayment rates in some
      settings. The precarious socioeconomic and health issues of PLWHA pose unique
      challenges to minimizing loan default risk. Carefully-designed clinical studies
      are needed to assess whether PLWHA can be as successful with microfinance as
      healthy individuals.

PMID- 20693741
TI  - Insurance coverage among people living with combined HIV/AIDS, chronic mental
      illness, and substance abuse disorders.
AB  - HIV triply-diagnosed adults (those with chronic mental illness and substance
      abuse disorders) must rely heavily on public insurance to cover high annual
      medical costs (approximately $50,000). This study examines the nature and
      determinants of insurance coverage (including managed care) for this population,
      along with annual transitions in coverage. Relative to people living with
      HIV/AIDS in general, fewer triply-diagnosed adults rely on private coverage (3%
      vs. 30%), but their rate of being uninsured is only slightly lower (16% vs. 20%).
      More than one third of such adults below poverty are uninsured-a matter of
      significant policy concern since the annual income of this group is less than 10%
      of the amount needed to cover their expected medical expenses. Those with the
      lowest mental health status were disproportionately represented in managed care.
      While coverage appears relatively stable over time, those with low incomes and
      moderate mental health status may face barriers in securing Medicaid.

PMID- 20693742
TI  - Assessing the mental health service needs of the homeless: a level-of-care
      approach.
AB  - OBJECTIVE: A level-of-care needs assessment was undertaken at Ontario's largest
      shelter to establish homeless clients' mental health service needs and identify
      service gaps. METHODS: A level-of-care planning model was applied to data on 356
      men. Assessments included the Colorado Client Assessment Record and a Service
      Needs and Use Questionnaire. RESULTS: Among the clients, 32% (N=105) were
      recommended for weekly support, 38% (N=125) for Intensive Case Management or
      Assertive Community Treatment, and 9% (N=29) for 24-hour supervision in a
      residential care facility. Despite on-site health services, half the men did not
      have their level of service need met. CONCLUSION: The wide range of unmet
      specialized mental health needs suggests that interventions of different
      structure and service intensity may be required for this population. A level-of
      care planning model may be a helpful tool for ensuring homeless clients are
      matched to appropriate services and supports.

PMID- 20693743
TI  - Tennessee HIV/AIDS people of color project.
AB  - The 25th anniversary of the acquired immunodeficiency syndrome (AIDS) in the
      United States occurred in 2006. Despite advances in detection, treatment, and
      care, AIDS, along with human immunodeficiency virus (HIV), and other sexually
      transmitted diseases (STDs) remain formidable opponents. Tremendous strides have
      been made in educating the public about associated risk factors and effective
      prevention methods. However, this has occurred less in communities of color. The
      paper describes collaboration among public health practitioners and academics to
      design and conduct research about HIV/AIDS needs and assets in Tennessee's
      communities of color.

PMID- 20693744
TI  - Health care access and utilization in older versus younger homeless adults.
AB  - OBJECTIVES: To examine whether demographic characteristics, health care access,
      and acute health care utilization differ by age among homeless adults. METHODS:
      We interviewed all 2,175 adult attendees of a citywide homeless outreach event.
      RESULTS: Older participants were more likely than younger participants to have a
      regular place for health care (59.8% vs. 44.3%, p<.01), a regular health care
      provider (53.6% vs. 35.6%, p<.01), and health insurance (45.5% vs. 32.1%, p<.01).
      Older participants were less likely to be unable to obtain needed health care
      (15.6% vs. 20.9%, p=.05). In a multivariate analysis, only lack of health
      insurance predicted inability to obtain needed care (AOR 2.9, CI 1.76-4.8).
      CONCLUSIONS: Older and younger homeless adults have similarly high rates of acute
      health care utilization. The better access to care among older homeless adults
      speaks to the importance of insurance in determining access to care among
      homeless adults.

PMID- 20693745
TI  - Sex and condom use in a large jail unit for men who have sex with men (MSM) and
      male-to-female transgenders.
AB  - Few data are available on factors contributing to sexual activity and condom use
      in custody settings, particularly among self-identified sexual minority
      prisoners. To address this gap, we undertook a study of sexual behavior and
      condom use of 101 randomly-selected men who have sex with men (MSM) and male-to
      female transgender inmates in a segregated Los Angeles jail unit that has weekly
      condom access. Most survey participants (53%) reported anal sex during custody.
      Although 65% of these reported using condoms, 75% also reported having sex
      without condoms. Qualitative interviews (n=17) indicate a wide range of reasons
      for participating in protected and unprotected sex during custody, the use of
      cues within the custody environment to assess potential partners' HIV status, and
      support for increased condom availability. Findings also indicate that high-risk
      sex occurs frequently in this unit and that condom distribution likely prevents a
      substantial amount of related HIV/STD risk.

PMID- 20693747
TI  - Neopterin and atherosclerotic plaque instability in coronary and carotid
      arteries.
AB  - Inflammation plays a key role in atherosclerosis and plaque vulnerability, and
      monocyte/macrophage activation contributes to these processes. Neopterin, a by
      product of the guanosine triphosphate pathway, is produced by activated
      macrophages on stimulation with interferon-gamma released from T lymphocytes, and
      is an activation marker for monocytes/macrophages. Coronary angiographic studies
      have shown a relationship between increased circulating levels of neopterin and
      the presence of complex coronary lesions in patients with unstable angina
      pectoris (UAP). Furthermore, in an immunohistochemical study performed using
      coronary atherectomy specimens, a significantly higher prevalence of neopterin
      positive macrophages was found in culprit lesions in patients with UAP than in
      those with stable angina pectoris (SAP). We recently clarified that the presence
      of complex carotid plaques detected by carotid ultrasound was related to
      increased circulating levels of neopterin, and immunohistochemical localization
      of neopterin was observed in complex carotid lesions obtained from carotid
      endarterectomy in patients with SAP. These findings suggest that neopterin is an
      important biomarker of plaque instability in both coronary and carotid
      atherosclerotic lesions.

PMID- 20693748
TI  - A significant association between impaired glucose metabolism and polymyalgia
      rheumatica.

PMID- 20693749
TI  - [Therapeutic cancer vaccines against gastro-intestinal cancer].

PMID- 20693750
TI  - [Virulence factors of Helicobacter pylori: up-to-date].

PMID- 20693751
TI  - [Current topics for H. pylori eradication therapy].

PMID- 20693752
TI  - [Usefulness of ultrasonography for diagnosis and treatment in case of superior
      mesenteric artery (SMA) syndrome].
AB  - A 37-year-old man, who had been admitted to another facility because of
      integration dysfunction syndrome suffered from postprandial epigastric pain,
      vomiting and weight loss. He was referred to our hospital for further
      examinations and treatment. Ultrasound examination revealed gastric and duodenal
      dilatation, reduction of the distance between the superior mesenteric artery
      (SMA) and aorta and to-and-fro movement in his duodenum, suggesting SMA syndrome.
      Computed tomography and upper gastrointestinal tract examination also showed
      findings typical of SMA syndrome. We measured the SMA-aorta distance and the
      passage of duodenal contents in various body positions using ultrasound. He had
      to-and-fro movements in his duodenum in a supine, sitting, and left recumbent
      position. However, when examined in the right recumbent position, the SMA-aorta
      distance became longest, and intestinal juice flowed from the duodenum to the
      jejunum. He underwent postural therapy, maintaining a right recumbent position
      for 30 minutes after every meal, which improved his clinical symptoms.

PMID- 20693753
TI  - [An imported Japanese case of cyclosporiasis].
AB  - A 42-year-old Japanese woman, who resided in Indonesia suffered from watery
      diarrhea. As soon as she returned to Japan, she had a medical examination at our
      hospital. Oocysts of Cyclospora cayetanensis were isolated from her stool on the
      14th day. Treatment with 1.6g/day sulfamethoxazole/trimethoprim combination for 1
      week was effective. Cyclosporiasis is a of newly-emerging infection and causes
      group infection or traveler's diarrhea. Cyclosporiasis should be suspected in
      patients with diarrhea who have returned from the endemic areas to Japan.

PMID- 20693754
TI  - [An autopsy case of alpha-fetoprotein-producing carcinoma of the sigmoid colon
      resulting in sudden death].
AB  - A 63-year-old woman was admitted to our hospital with complaints of abdominal
      distention and bilateral cervical masses. Her serum AFP was 11700 ng/dl. AFP was
      confirmed immunohistochemically by biopsy of a sigmoid colon tumor, yielding a
      diagnosis of AFP-producing carcinoma of the sigmoid colon, accompanied by
      multiple liver metastases, and systemic multiple lymph node metastases. Due to
      her poor general condition with mitral regurgitation, the patient began S-1
      treatment. The patient's general condition rapidly worsened after 1 course of S-1
      had no effect. She died on the 59th hospital day and a pathological autopsy was
      performed. We examined 67 cases of AFP-producing colon cancer in Japan, including
      our own, and report the findings with references.

PMID- 20693755
TI  - [A case of Diphyllobothrium nihonkaiense identified by virtual enterography and
      virtual enteroscopy].
AB  - In October 2007, a woman in her early 30s presented, complaining of worm
      discharge in her stool. We identified it as Diphyllobothrium nihonkaiense, and
      identified it by virtual enterography and virtual enteroscopy. It was treated by
      1500 mg/day praziquantel orally. We think these methods, of pathology as well as
      capsule enteroscopy and enteroscopy, are useful for the searching of the small
      intestinal lesions. We hope these examinations will become more widespread with
      reference to these cases.

PMID- 20693756
TI  - [An adult with chronic active Epstein-Barr virus infection associated with
      repeated liver dysfunction].
AB  - A 30-year-old woman with hepatitis for 5 months was admitted to our hospital. She
      had been given a diagnosis of liver dysfunction 2 years previously, and the
      hepatitis in this case was believed to be drug-induced. On admission, the patient
      was asymptomatic. Serologic tests for hepatitis A, B, and C were negative, and
      the laboratory results showed a WBC count of 7600/mm3 (lymphocytes, 85%), an AST
      level of 559 U/L, ALT level of 427 U/L, and EBV-DNA of 2.9x10(6) copies/microg
      DNA. Histopathological examination of the liver biopsy specimens revealed
      moderate lymphocyte infiltration in the sinusoids and positive Epstein-Barr
      encoded RNA (EBER) -lymphocytes. Therefore, chronic active Epstein-Barr virus
      infection (CAEBV) was diagnosed. However, 9 months after the diagnosis she died
      of mycotic sepsis. We presume that the patient may have developed CAEBV at the
      prior diagnosis of liver dysfunction 2 years previously. Therefore, CAEBV
      associated with liver dysfunction should be considered during the differential
      diagnosis of patients showing persistent liver dysfunction.

PMID- 20693757
TI  - [A case of cardiac sarcoidosis occurring during combination therapy by IFN alpha
      and ribavirin for chronic hepatitis C].
AB  - A 72-year-old woman received combination therapy with peginterferon alpha and
      ribavirin for treatment of chronic hepatitis C. Approximately 40 weeks after
      starting treatment, she developed an eruption in the left inner canthus and
      sarcoidosis was diagnosed after biopsy of the eruption. Combination therapy was
      discontinued, and further detailed examinations revealed bilateral hilar
      lymphadenopathy, uveitis, and complete atrioventricular block. A permanent
      cardiac pacemaker was implanted, and her sarcoidosis improved upon administration
      of corticosteroids.

PMID- 20693758
TI  - [A case of acinar cell carcinoma diagnosed by endoscopic ultrasound-guided fine
      needle aspiration prior to surgical treatment].
AB  - A 65-year-old woman was admitted with upper abdominal pain and pyrexia. She was
      given a diagnosis of acute pancreatitis and treated with intravenous infusion.
      After recovering, abdominal enhanced-CT showed a low density area in the head of
      the pancreas, measuring 2 cm in maximum dimension. Endoscopic ultrasound guided
      fine-needle aspiration (EUS-FNA) revealed acinar cell carcinoma (ACC). She
      underwent curative subtotal stomach-preserving pancreaticoduodenectomy. The
      definitive diagnosis, based on the histopathological examinations including
      immunohistochemical staining, was ACC. ACC of the pancreas is extremely rare,
      occurring in approximately 1% of all cases of pancreatic neoplasm. We report a
      rare case diagnosed as ACC by EUS-FNA prior to surgical treatment.

PMID- 20693759
TI  - [A case of acute pancreatitis after extracorporeal shock wave lithotripsy for
      renal pelvic calculus].
AB  - A 62-year-old man was admitted to receive extracorporeal shock wave lithotripsy
      (ESWL) for a right renal pelvic calculus. During the operation, the patient
      complained of right upper quadrant pain. Later in the day, laboratory data showed
      elevated serum amylase levels, and abdominal CT revealed an enlarged pancreas.
      These findings led to a diagnosis of acute pancreatitis. The following day, urine
      output had decreased, and pleural and ascitic fluid had accumulated. For these
      reasons, the patient was transferred to our hospital to receive combination
      therapy, including arterial infusion therapy with protease inhibitors,
      antibiotics and continuous hemodiafiltration. The condition of the patient
      improved, and he was discharged on day 30. Acute pancreatitis should be
      considered as an early complication after ESWL for urinary tract calculus.

PMID- 20693760
TI  - [Picture in clinical hematology no.4: Disseminated atypical mycobacterium
      infection in a case with AIDS].

PMID- 20693761
TI  - [Intravascular large B-cell lymphoma; recent advances and future perspectives].

PMID- 20693762
TI  - [Treatment strategy for childhood and adolescent acute lymphoblastic leukemia in
      first remission].

PMID- 20693763
TI  - [Treatment strategy for the patients with Philadelphia chromosome negative acute
      lymphoblastic leukemia in first remission].

PMID- 20693764
TI  - [A decision analysis of validity of allogeneic hematopoietic stem cell
      transplantation from an HLA-matched sibling donor for adult acute lymphoblastic
      leukemia in first remission].

PMID- 20693765
TI  - [Treatment for AML in first remission].

PMID- 20693766
TI  - [Autologous peripheral blood stem cell transplantation as a treatment choice for
      adult acute myelogenous leukemia].

PMID- 20693767
TI  - [Classification of T/NK-cell malignancies: Japanese perspective].

PMID- 20693768
TI  - [International consensus on the management of adult T-cell leukemia-lymphoma].

PMID- 20693769
TI  - [Concurrent chemoradiotherapy for localized nasal NK/T-cell lymphoma].

PMID- 20693770
TI  - [Clinical features and gene mutation status of polycythemia vera and essential
      thrombocythemia in Japan].

PMID- 20693771
TI  - [Clinical manifestations and treatment of chronic eosinophilic leukemia
      (CEL)/idiopathic hypereosinophilic syndrome (HES) in Japan].

PMID- 20693772
TI  - [Molecular biology of juvenile myelomonocytic leukemia (JMML)].

PMID- 20693773
TI  - [Molecular genetics of congenital anomaly syndromes (RAS/MAPK syndromes)
      complicated with malignancies].

PMID- 20693774
TI  - [DNA damage response and hematological malignancy].

PMID- 20693775
TI  - [Mechanisms of genomic instability in Fanconi anemia].

PMID- 20693776
TI  - [Hematological malignancies in congenital neutropenia].

PMID- 20693777
TI  - [Secondary chronic myelogenous leukemia following postoperative TS-1 therapy for
      advanced gastric cancer].
AB  - A 78-year-old man received total gastrectomy for advanced gastric cancer in
      September 2006, and was subsequently treated with oral anti-metabolite TS-1 for
      38 months. He had no evidence of recurrence of gastric cancer, although he had a
      continuous poor appetite due to TS-1. Leukocytosis was found in November 2008. On
      the basis of bone marrow findings, Philadelphia chromosome and BCR-ABL fusion
      gene, he was diagnosed as having chronic phase of secondary chronic myeloid
      leukemia (CML). Two weeks after starting imatinib therapy, skin eruption,
      palpebral edema and appetite loss were observed; moreover, thrombocytopenia
      gradually worsened. He stopped taking imatinib and hydroxyurea was subsequently
      started. The above symptoms disappeared and the platelet count normalized. CML is
      rare in secondary leukemia. Our case is the second reported case of secondary CML
      following TS-1 treatment and suggests that therapy for secondary CML should be
      selected on the basis of QOL in patients with advanced cancer.

PMID- 20693778
TI  - [Primary neurolymphomatosis of the cervical nerve root].
AB  - A 74-year-old woman was admitted with muscle weakness and sharp pain in her upper
      limbs. On (18)FDG-PET, abnormal accumulation was noted on both sides of the
      brachial plexus at the cervical spinal cord. A diagnosis of primary peripheral
      nerve neurolymphomatosis was made based on biopsy of the third cervical nerve.
      Following R-CHOP therapy, the abnormal accumulation of (18)FDG-PET scan
      disappeared. However, disturbance of consciousness occurred 6 months later and
      recurrence as multiple brain tumors was detected. Although salvage chemotherapy
      was performed, the patient died of overwhelming sepsis. Primary peripheral nerve
      neurolymphomatosis is extremely rare. Early distinct diagnosis using (18)FDG-PET
      and combination chemotherapy of rituximab and high dose methotrexate may improve
      the outcome for such patients.

PMID- 20693779
TI  - Should blood gas analysis be part of the diagnostic workup of short children?
      Auxological data and blood gas analysis in children with renal tubular acidosis.
AB  - BACKGROUND: Renal tubular acidosis (RTA) is a rare cause of growth failure,
      therefore it is uncertain whether routine screening with blood gas analysis of
      short infants and children is cost-effective. OBJECTIVE: To investigate the
      clinical, growth and laboratory parameters in children with RTA to estimate the
      possible value of laboratory screening for this disorder in infants and children
      referred for short stature according to a recent guideline. METHOD: Retrospective
      chart analysis of 30 children diagnosed between 1978 and 2005 in The Netherlands
      and 3 centers in Belgium. RESULTS: The current guideline for short stature
      detected 33% of children with RTA. Assuming a pre-test probability of RTA of 0.6
      per 100,000 births, the likelihood ratio of poor growth was 58 and 17 below and
      above 3 years, respectively. Sensitivity was 17/30 and 12/24 for a -2.0 SDS
      cutoff for weight and body mass index, respectively. In infants and toddlers
      diagnosed before 3 years of age, the mean weight loss was 1.5 SD, and 0.8 SDS in
      older children. In short children >3 years RTA was extremely rare, always
      associated with clinical symptoms, and rarely detected by blood gas analysis.
      CONCLUSION: According to our data a decreasing weight SDS for age is a sufficient
      indication to perform blood gas analysis in children <3 years of age,
      particularly in the presence of additional clinical features, whereas it can be
      omitted in short children >3 years of age.

PMID- 20693780
TI  - A rare case of centric fission and fusion in a river buffalo (Bubalus bubalis, 2n
      = 50) cow with reduced fertility.
AB  - A 5-year-old river buffalo cow underwent cytogenetic investigation since it had
      only one male offspring, apparently with normal body constitution, which died one
      month after birth. The female carrier had normal body conformation and internal
      sex adducts, as revealed by rectal palpation performed by a specialist veterinary
      practitioner. The cow was found to carry a complex and rare chromosome
      abnormality. Indeed, a centric fission of one river buffalo (BBU) chromosome 1
      with a subsequent (or simultaneous) centric fusion of BBU1p with BBU23 was
      revealed by both RBA-banding and specific molecular markers of BBU1p (DEFB1) and
      BBU23 (ACTA2). CBA-banding revealed a pale, very small C-band in the der1 (BBU1q)
      and a prominent C-band on the new biarmed chromosome originated by rob(1p;23).
      Both telomeric probes and AgNOR staining confirmed the Robertsonian translocation
      (rob), both FITC-signals and the NORs (BBU23) being telomerically located.
      Furthermore, telomeric signals on der1 (BBU1q) indicate that these 2 chromosomal
      events may be the result of a reciprocal translocation which occurred between
      BBU1 and BBU23.

PMID- 20693781
TI  - Conflict in cingulate cortex function between humans and macaque monkeys: More
      apparent than real.

PMID- 20693782
TI  - Conflict over cingulate cortex: Between-species differences in cingulate may
      support enhanced cognitive flexibility in humans.

PMID- 20693783
TI  - Individual behavioral and neuronal phenotypes for arginine vasotocin mediated
      courtship and aggression in a territorial teleost.
AB  - The neuropeptide arginine vasotocin (AVT) is well known to modulate both
      aggression and affiliation, yet few studies relate individual behavioral state to
      a quantitative assessment of AVT distribution in the brain. Here, using a wild
      population of beaugregory damselfish, Stegastes leucostictus, we assess: (1) the
      effect of AVT on courtship, and (2) with reference to our previous study on AVT
      modulation of aggression in this species, the relationship between AVT-like
      immunoreactive (ir) fiber distribution in the forebrain's preoptic area and
      individual courtship and aggression levels. Exogenous AVT did not affect
      courtship, yet Manning compound, an arginine vasopressin (AVP) V1a receptor
      antagonist, significantly lowered but did not eradicate courtship. Consistent
      with AVT's known facilitation of aggression in this species, the density of AVT
      ir fibers in the preoptic area was significantly negatively correlated to
      aggression. Our findings match similar behavioral and immunoreactive patterns of
      neuropeptide secretion in other taxa. Unlike aggression, preoptic AVT-ir fiber
      density was not significantly correlated to individual courtship levels. The
      results suggest a differential involvement of preoptic AVT neurons and/or their
      receptors in supporting the expression of aggression and courtship.

PMID- 20693784
TI  - Comparative morphology of the mechanosensory lateral line system in a clade of
      New Zealand triplefin fishes.
AB  - The mechanoreceptive lateral line system in fishes detects hydrodynamic stimuli
      and plays a critical role in many fundamental behaviours, including orientation
      to water currents and the detection of stationary objects, prey and predators.
      Interspecific variation in lateral line structure may result from a process of
      functional adaptation, with the background level of hydrodynamic activity
      proposed as an important selective pressure. Here we use the eight species of the
      ecologically diverse New Zealand marine triplefin fish of the genus Forsterygion
      and one species from the sister genus Notoclinops to investigate interspecific
      differences in lateral line morphology and to assess the relationship between
      lateral line characteristics and exposure to wave energy (fetch/depth ratio).
      Overall, the results show that lateral line traits are divergent between species,
      and these differences could in part be related to the wave exposure of the
      habitats that the species occupy. Specifically, numbers of canal neuromasts
      differed significantly between species, and most canal groupings increased in
      neuromast number with fetch/depth ratio, while the number and area of some
      superficial neuromast groupings decreased significantly with exposure.
      Distribution of superficial neuromasts along the trunk in the semi-pelagic and
      paedomorphic species F. maryannae differed from the other, demersal species,
      which may be associated with the unique lifestyle of this species and/or
      developmental processes. Canal architecture also differed considerably between
      species, but displayed no relationship with fetch/depth ratio. The results from
      this study indicate that some interspecific differences in lateral line organs
      may be a by-product of selection for habitat divergence. Future work should
      explore additional causal factors that might have influenced the evolution of
      lateral morphology in these species, including phylogenetic and allometric
      effects.

PMID- 20693785
TI  - The Johann Jakob Wepfer Award 2010 of the European Stroke Conference to Professor
      Jan van Gijn.

PMID- 20693786
TI  - Facts versus theories: an everlasting struggle. The Johann Jakob Wepfer Award
      2010.
AB  - Rather than a complete overview of the contribution of Utrecht to stroke
      research, I have selected a few subjects and attempt to put these in historical
      context. Johann Jakob Wepfer (1620-1695) was unique in that he approached
      'apoplexy' through post-mortem observations, in the tradition of Padua. However,
      the interpretation of his findings in haemorrhagic and especially non
      haemorrhagic stroke was still heavily influenced by the authority of Galen's
      writings. Wepfer's category of 'serous apoplexy' assumed that extravasation of
      blood serum might lead to compression of brain substance and blockage of 'nerve
      pores' through which mental 'spirit' was supposed to flow. This notion of
      'cerebral congestion' or 'cerebral hyperaemia' lived on, at least to the middle
      of the 20th century! The pitfalls of theorizing are also evident from recent
      history (the facile assumption that cerebral ischaemia occurs in the same way as
      leg ischaemia). By implication, similar errors may well be hidden in present
      ideas about stroke. Probable or possible examples are the idees recues that 30 mg
      of aspirin is less efficacious in the secondary prevention of stroke than 100 mg,
      that vasospasm is the cause of delayed ischaemia after aneurysmal subarachnoid
      haemorrhage and that perimesencephalic haemorrhage is not caused by rupture of an
      artery. Physicians still speculate more often than they care to admit.

PMID- 20693787
TI  - Report of the 19th European Stroke Conference, Barcelona, May 25-28, 2010.

PMID- 20693789
TI  - Time trends in hospital-referred stroke and transient ischemic attack: results of
      a 7-year nationwide survey in France.
AB  - BACKGROUND: Nationwide evaluations of the burden of stroke are scarce. We aimed
      to evaluate trends in stroke and transient ischemic attack (TIA) hospitalization,
      in-hospital case fatality rates (CFRs) and mortality rates in France during 2000
      2006. METHODS: Hospitalizations for stroke and TIA were determined from National
      Hospital Discharge Diagnosis Records that used the International Classification
      of Disease, 10th revision, codes I60, I61, I63, I64, G45, G46. CFRs and mortality
      rates were estimated from the national death certificates database. RESULTS: The
      total number of stays for stroke increased between 2000 and 2006 (88,371 vs.
      92,118) contrasting with a decrease in that for TIA. The age-standardized
      (European population) hospitalization rates for TIA decreased in men (52.2 vs.
      44.5/100,000/year, p = 0.002), whereas they remained stable in women (32.4 vs.
      31.0/ 100,000/year). Concerning stroke, a decrease in hospitalization rates was
      observed in both men (from 135.3 to 123.4/ 100,000/year, p < 0.001) and women
      (from 85.1 to 80.7, p < 0.001). Whatever the age group and the sex, a sharp
      decrease in in-hospital stroke CFRs was noted. In addition, a 23% decrease in
      mortality rates was observed. This decrease was greater in patients >65 years.
      CONCLUSION: Our results demonstrate a decline in hospitalization rates for
      stroke, and in both stroke CFRs and mortality rates between 2000 and 2006.
      Improvements in stroke prevention and acute stroke care may have contributed to
      these results, and may have been initiated by recent advances in health policy
      with regard to this disease in France.

PMID- 20693790
TI  - Real-time hemodynamic assessment of downstream effects of intracranial stenoses
      in patients with orthostatic hypoperfusion syndrome.
AB  - BACKGROUND: Arterial flow velocity changes on transcranial Doppler can reflect
      changes in cerebral flow during position-induced ischemia if obtained during
      short-term monitoring of positional changes. SUBJECTS AND METHODS: Our
      multicenter group monitored symptomatic and asymptomatic arteries in patients
      with recurrent neurological deficits during positional changes and documented
      intracranial arterial stenosis. Bilateral posterior cerebral and middle cerebral
      arteries were monitored dependent on clinical symptom localization. The
      symptomatic artery was monitored distal to the intracranial stenosis, and mean
      flow velocities (MFV) were recorded at different body positions. The symptomatic
      artery relative MFV ratio was defined as the ratio of symptomatic artery MFV in
      the asymptomatic position--MFV in the symptomatic position/MFV in the
      asymptomatic position. RESULTS: Sixteen patients underwent transcranial Doppler
      monitoring: mean age 62 +/- 19 years, 11 (69%) men, 6 (40%) with transient
      ischemic attacks. Ten patients (63%) had posterior and 6 anterior circulation
      symptoms. Patients developed neurological symptoms while standing up (63%) and/or
      sitting (44%), walking (13%) or during neck extension (6%). Symptomatic artery
      MFV dropped by > or =25% from the resting to the symptomatic position in all
      patients except for one. The mean symptomatic artery MFV relative ratio was
      higher compared with the mean asymptomatic artery MFV relative ratio: 0.5 +/-
      0.28 versus -0.02 +/- 0.1 (p = 0.001, Wilcoxon test). The symptomatic artery
      relative ratio of >0.25 had a 94% sensitivity and 100% specificity for predicting
      neurological symptom development during testing (kappa = 0.9, p < 0.001).
      CONCLUSIONS: A significant reduction in intracranial flow velocity distal to an
      intracranial stenosis can identify patients whose symptoms can worsen with
      positional changes. These patients may prove a target for interventional
      revascularization techniques.

PMID- 20693792
TI  - Atherosclerotic vascular disease rather than metabolic syndrome predicts ischemic
      stroke in diabetic patients.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to evaluate the effect of
      metabolic syndrome on ischemic stroke in Chinese subjects with type 2 diabetes.
      METHODS: Anthropometric parameters (waist circumference and body mass index),
      blood pressure, and plasma biochemical (lipid and glycemic profiles) were
      collected. Subjects with type 2 diabetes were categorized by the criteria of the
      updated Adult Treatment Panel III (ATP III) with the modified definitions of
      obesity in Asians. Transcranial Doppler was performed to define middle cerebral
      artery stenosis. RESULTS: Of 2,197 patients (age 55.4 +/- 11.3 years; male 40.8%;
      median follow-up period 8.7 years, interquartile range 7.8-9.5 years) without
      symptoms of cerebrovascular disease, evidence of middle cerebral artery stenosis
      was identified in 272 subjects (12.4%). According to NCEP ATP III criteria, 1,324
      (60.3%) patients had MetS at baseline. Ischemic stroke occurred in 184 (8.4%,
      184/2197) patients during follow-up. Patients with incident stroke had a higher
      prevalence of MetS compared with those without stroke (p = 0.004), and the number
      of components of MetS was also significantly increased in patients with stroke (p
      = 0.001). Cox regression demonstrated that MetS was not associated with incident
      stroke. CONCLUSIONS: In Chinese type 2 diabetic patients, metabolic syndrome does
      affect stroke occurrence with a higher stroke incidence among those with
      metabolic syndrome, but stroke occurrence seems to be better explained by other
      vascular risk factors than by metabolic syndrome.

PMID- 20693791
TI  - Longitudinal trajectories of cognitive decline among older adults with
      cardiovascular disease.
AB  - BACKGROUND: The long-term course of cognitive impairments secondary to
      cardiovascular disease (CVD) is unclear. In this study, we prospectively
      investigated the temporal pattern, rate and hierarchy of cognitive decline
      attributable to CVD--a risk factor for the development of vascular cognitive
      impairment (VCI)--and examined the influence of cardiac surgery and heart failure
      on cognitive decline. METHODS: A total of 172 older adults with CVD were
      administered a comprehensive battery of neuropsychological tests at study entry,
      and at 12 and 36 months thereafter. Random coefficient regressions were used to
      investigate the temporal course, rate and hierarchy of cognitive decline, as well
      as to examine the effect of heart failure (reported by 21% of the sample) and
      cardiac surgery (reported by 44% of the sample) on trajectories of cognitive
      change. RESULTS: The course of decline in cognition was linear for language and
      attention-executive function-psychomotor speed, and curvilinear for visuospatial
      abilities, memory and overall cognition. The decline in attention-executive
      function-psychomotor speed was smaller than the decline in other domains. The
      greatest decline occurred in visuospatial abilities. The rate of decline in
      cognition was not altered by a history of heart failure. Patients who had
      undergone cardiac surgery exhibited slower deceleration in their rates of decline
      in overall cognition. At baseline, patients with a history of heart failure had
      comparatively poorer attention-executive function-psychomotor speed, overall
      cognition and, to a lesser extent, visuospatial scores. CONCLUSION: There is
      measurable decline in neurocognitive function among patients with CVD. This
      decline is linear in some cognitive domains and curvilinear in others and is not
      attributable to the normal aging process. Cardiac surgery, but not heart failure,
      significantly affects the trajectory of cognitive decline. Because most vascular
      risk factors are modifiable, preventive measures such as lifestyle changes may be
      useful in retarding cognitive decline among patients with CVD, thus preventing
      the onset of VCI.

PMID- 20693793
TI  - Wallerian degeneration of pyramidal tract after paramedian pons infarct.
AB  - BACKGROUND: The intention of this study was the prospective analysis of Wallerian
      degeneration of the pyramidal tract after paramedian pons infarction. METHODS:
      Patients with paramedian pons infarct underwent MR imaging including diffusion
      tensor imaging at admission and got 1-3 MR scans up to 6 months of follow-up.
      Clinical scores and transcranial magnetic stimulation were acquired in the acute
      phase and 3-6 months later. The pyramidal tracts were manually segmented in
      fractional anisotropy (FA) color maps after coregistration of all MR datasets of
      each patient. FA as well as axial and radial diffusivity were measured in the
      volume of lesioned and contralateral pyramidal tracts distally to the ischemic
      lesion. RESULTS: From 11 patients studied, 7 developed Wallerian degeneration
      detected as statistically significant decrease in FA over time in the distal
      pyramidal tract. Wallerian degeneration could be detected at the earliest between
      the first and the third days after the onset of symptoms. A continuous decrease
      in FA and an increase in axial and radial diffusivity in degenerating pyramidal
      tracts over time were demonstrated. A significant correlation between NIHSS score
      on admission and the slope of relative axial diffusivity and a significant
      correlation between motor-evoked potential amplitudes of the arm on admission and
      the outcome relative FA was found. CONCLUSIONS: The initial MR image cannot
      predict the following Wallerian degeneration. However, the severity of motor
      disturbance and the motor-evoked potential of the arm on admission could be
      possible parameters to predict Wallerian degeneration. For estimation of
      Wallerian degeneration over time, at least 2 diffusion tensor imaging
      measurements have to be done at different time points.

PMID- 20693794
TI  - Pathophysiological determinants of worse stroke outcome in atrial fibrillation.
AB  - BACKGROUND: The reasons for worse outcome following ischemic stroke in patients
      with atrial fibrillation (AF) remain unclear. We aimed to elucidate the
      pathophysiological determinants of poorer stroke outcome in patients with AF
      using systematic MRI data from the Echoplanar Imaging Thrombolytic Evaluation
      Trial (EPITHET). METHODS: Comparisons of infarct size, hypoperfusion volume,
      infarct growth, arterial occlusion, recanalization, reperfusion, hemorrhagic
      transformation and stroke severity were made between patients with and without AF
      enrolled in the EPITHET study. RESULTS: AF was present in 42 of 101 patients. At
      baseline, AF patients were older (79 vs. 73 years, p = 0.02), had more severe
      neurological impairment (National Institutes of Health Stroke Scale score 16 vs.
      11, p = 0.006), larger infarcts (29 vs. 15 ml, p = 0.04) and greater volumes of
      more severe hypoperfusion (T(max) > or =8 s, perfusion-weighted imaging volume 70
      vs. 43 ml, p = 0.01) compared to patients without AF. There were no significant
      differences in arterial occlusion site, infarct growth, recanalization or
      reperfusion. At outcome, AF patients had larger infarcts (52 vs. 16 ml, p =
      0.05), more severe hemorrhagic transformation (29 vs. 5%, p = 0.002 for
      parenchymal hematomas), greater disability (modified Rankin Scale score 4 vs. 3,
      p = 0.03) and higher mortality rates (31 vs. 12%, p = 0.04). AF was an
      independent predictor of parenchymal hematoma (OR = 6.90, 95% CI = 1.57-30.25),
      but not mortality (OR = 2.56, 95% CI = 0.83-7.85). CONCLUSIONS: Patients with AF
      have worse clinical and imaging outcomes following ischemic stroke. This study
      suggests that the adverse effect of AF is due to greater volumes of more severely
      hypoperfused tissue, leading to larger infarct size and greater risk of severe
      hemorrhagic transformation.

PMID- 20693795
TI  - Proliferation activity is significantly elevated in partially embolized cerebral
      arteriovenous malformations.
AB  - BACKGROUND: The natural history of cerebral arteriovenous malformations (AVMs) is
      yet to be determined. It has been shown that angiogenic factors are involved in
      the pathogenesis of AVMs, in particular in partially embolized lesions. This
      study was conducted to investigate the expression of angiogenic and proliferative
      factors in relation to different clinical conditions and treatment modalities.
      METHODS: Immunohistochemistry was performed for 145 consecutive cases of cerebral
      AVMs. The specimens were stained with antibodies against VEGF, bFGF, Ki 67, CD 34
      and CD 31. Expression was correlated with clinical presentation (haemorrhage,
      seizures or other symptoms), AVM localization, size, eloquence and venous
      drainage, as well as with preoperative AVM embolization. RESULTS: Whereas no
      correlation was found between the expression of angiogenic factors and different
      clinical conditions, we observed a significantly increased proliferation activity
      as shown by Ki 67 expression in patients with intracerebral haemorrhage (p =
      0.02) and in patients with preoperative embolization (p = 0.02). CONCLUSIONS:
      Increased proliferation activity in partially embolized AVMs supports a 'no
      touch' strategy and clinical observation in high-risk AVMs and demands complete
      AVM elimination in treatable lesions.

PMID- 20693796
TI  - Minimizing wound contamination in a 'clean' surgery: comparison of chlorhexidine
      ethanol and povidone-iodine.
AB  - PURPOSE: There is limited work analyzing the efficacy of different antiseptics in
      reducing wound contamination by the skin flora during hernia repair and its
      influence on the incidence of wound infection, which continues to be a major
      problem in the developing world. This study was designed to test if chlorhexidine
      ethanol has superior antimicrobial efficacy compared with povidone-iodine.
      METHODS: In a prospective randomized trial, the efficacy of chlorhexidine-ethanol
      and povidone-iodine in the reduction of colony counts of the skin flora and the
      incidence of surgical site infection was compared. RESULTS: Both povidone-iodine
      and chlorhexidine-ethanol produced significant reduction in the skin bacterial
      colony counts, from 18.66 x 10(2) to 2.34 x 10(2) colony-forming units with
      povidone-iodine (59%) and from 12.34 x 10(2) to 0.93 x 10(2) colony-forming units
      (82%) with chlorhexidine-ethanol. Infection rates with the use of povidone-iodine
      and chlorhexidine-ethanol groups were not significantly different (9.5 vs. 7.0; p
      = 0.364). The reduction in colony counts in those who developed infection was
      only 15.6% compared with 77.1% in those who did not develop infection.
      CONCLUSIONS: The antibacterial efficacy of chlorhexidine-ethanol and povidone
      iodine is comparable in open hernia repair.

PMID- 20693797
TI  - Transforming growth factor alpha stimulation of mucosal tissue cultures from head
      and neck squamous cell carcinoma patients increases chemoresistance to cisplatin.
AB  - The monoclonal epidermal growth factor receptor (EGFR) antibody cetuximab
      (Erbitux) was recently approved by the European Medicines Agency for the
      treatment of recurrent and/or metastatic head and neck squamous cell carcinoma
      (HNSCC) in combination with a platinum-based chemotherapy. Since the antibody has
      only a limited effect as a monotherapy, possible explanations for the synergistic
      effect with cisplatin are enhanced antibody-dependent cytoxicity and increased
      sensitivity to the drug. Most of our knowledge of EGFR biology in HNSCC is based
      on studies using EGFR inhibitors and/or antibodies. Our study was designed to
      evaluate the impact of EGFR stimulation on cisplatin-induced DNA damage.
      Therefore, tissue cultures were produced of tumor-free oropharyngeal mucosa
      biopsies of HNSCC patients and controls. In a previous study, overexpression of
      EGFR in tissue cultures from tumor patients compared to controls was confirmed by
      immunohistochemical staining. Twenty-four-hour stimulation of tissue cultures
      with transforming growth factor alpha (TGF-alpha), a specific EGFR ligand,
      resulted in a reduction of cisplatin-induced DNA damage by 35% in cases, whereas
      in controls TGF-alpha had no effect. This reflects a statistically significant
      increase in cellular chemoresistance to cisplatin following TGF-alpha stimulation
      and helps to further understand effects of EGFR antisense therapy in combination
      with chemotherapy.

PMID- 20693798
TI  - Prevalence of multidrug-resistant bacteria at a tertiary-care teaching hospital
      in Mexico: special focus on Acinetobacter baumannii.
AB  - Our aim was to determine the prevalence of multidrug resistance of Acinetobacter
      baumannii and other pathogens at a tertiary-care teaching hospital in Mexico over
      a 3-year period. Clinical isolates of A. baumannii (n = 550), Pseudomonas
      aeruginosa (n = 250), some Enterobacteriaceae species (n = 500) and
      Staphylococcus aureus (n = 250) collected over a 3-year period were included.
      Susceptibility tests were performed by the broth microdilution method. 74% of A.
      baumannii, 40% of Escherichia coli, 34% of P. aeruginosa, 22% of Klebsiella
      pneumoniae, 9% of Enterobacter cloacae, and 7% of Serratia sp. were multidrug
      resistant. 59% of A. baumannii clinical isolates were meropenem-resistant. A.
      baumannii isolates from the lower respiratory tract were the most susceptible,
      followed by urine clinical isolates. Species from Enterobacteriaceae showed
      susceptibility rates higher than 90% to meropenem and tigecycline and Serratia
      sp. showed the highest susceptibility to the drugs evaluated. For P. aeruginosa,
      the most potent drug was levofloxacin, followed by meropenem and piperacillin
      tazobactam. With regard to S. aureus, 96% of the isolates were susceptible to
      vancomycin, followed by tigecycline and minocycline (91% of strains susceptible).
      The high multidrug resistance observed underscores the need for surveillance of
      bacterial drug resistance.

PMID- 20693799
TI  - QT prolongation and serum sotalol concentration are highly correlated following
      intravenous and oral sotalol.
AB  - OBJECTIVES: The aim of this study was to evaluate the correlation between QT
      interval (QT) and serum sotalol concentration following a single low dose of oral
      and intravenous sotalol. METHODS: Fifteen healthy volunteers received 75 mg
      intravenous sotalol over 2.5 h and 80 mg oral sotalol in a random order. Serum
      sotalol concentrations and 12-lead electrocardiograms were obtained
      simultaneously at baseline and 7 times following dosings. Rate-corrected QT (QTc)
      was calculated by the Bazett, Fridericia and Framingham formulas. Linear
      regression analysis was performed between sotalol concentrations and QT
      measurements. RESULTS: Significant QT prolongation was seen at very low sotalol
      doses and serum concentrations. QTc intervals calculated by the Framingham and
      Fridericia formulas showed the strongest and virtually identical correlations
      with serum sotalol concentration (r >or= 0.97, p < 0.001) following oral and
      intravenous administrations. The equation QTc = 0.0342 (sotalol concentration) +
      398 closely predicted actual QTc at any sotalol concentration. CONCLUSIONS: A
      strong correlation was observed between serum sotalol concentration and QTc
      prolongation across the entire concentration range. Low-dose sotalol caused
      significant QT prolongation. At similar concentrations, intravenous and oral
      sotalol caused similar QT and QTc effects. Knowing the QT effect can be used to
      guide further dose increase.

PMID- 20693800
TI  - Detection of coronary artery disease in patients with a permanent pacemaker.

PMID- 20693801
TI  - Accuracy and long-term prognostic value of pacing stress echocardiography
      compared with dipyridamole tl201 emission computed tomography in patients with a
      permanent pacemaker and known or suspected coronary artery disease.
AB  - OBJECTIVES: Myocardial ischemia is difficult to assess by noninvasive methods in
      patients with a permanent pacemaker. Pacing stress echocardiography (PASE) has
      been used successfully in the detection of coronary artery disease (CAD).
      However, there are no data comparing PASE and other methods. METHODS: We compared
      agreement and accuracy of PASE and radionuclide tomography (SPECT) in detecting
      CAD in 58 patients, mean age 75 +/- 7 years, with a permanent pacemaker and known
      or suspected CAD. Thirty-nine patients underwent coronary angiography. The
      prognostic value of these tests was determined by prediction of cardiac events
      and cardiac death. RESULTS: PASE and SPECT were positive in 39 and 43 patients,
      respectively. The agreement between the tests was 75%; kappa value 0.64. The
      sensitivity was 87 and 96% and the specificity 78 and 57%, respectively. With
      median follow-up of 51 months, there were 24 cardiac events and 8 cardiac deaths.
      Multivariable analysis determined that positive PASE was the only independent
      predictive factor associated with cardiac events and cardiac death. CONCLUSIONS:
      PASE is a feasible and effective method for detection of significant CAD in
      patients with permanent-pacemaker and allows effective risk stratification. PASE
      merits further study in larger prospective comparative studies.

PMID- 20693802
TI  - Hypothyroid pericardial effusion: multifactorial pathogenesis.

PMID- 20693803
TI  - Basal ganglia volume is associated with aerobic fitness in preadolescent
      children.
AB  - The present investigation is the first to explore the association between
      childhood aerobic fitness and basal ganglia structure and function. Rodent
      research has revealed that exercise influences the striatum by increasing
      dopamine signaling and angiogenesis. In children, higher aerobic fitness levels
      are associated with greater hippocampal volumes, superior performance on tasks of
      attentional and interference control, and elevated event-related brain potential
      indices of executive function. The present study used magnetic resonance imaging
      to investigate if higher-fit and lower-fit 9- and 10-year-old children exhibited
      differential volumes of other subcortical brain regions, specifically the basal
      ganglia involved in attentional control. The relationship between aerobic
      fitness, dorsal and ventral striatum volumes and performance on an attention and
      inhibition Eriksen flanker task was also examined. The results indicated that
      higher-fit children showed superior flanker task performance compared to lower
      fit children. Higher-fit children also showed greater volumes of the dorsal
      striatum, and dorsal striatum volume was negatively associated with behavioral
      interference. The results support the claim that the dorsal striatum is involved
      in cognitive control and response resolution and that these cognitive processes
      vary as a function of aerobic fitness. No relationship was found between aerobic
      fitness, the volume of the ventral striatum and flanker performance. The findings
      suggest that increased childhood aerobic fitness is associated with greater
      dorsal striatal volumes and that this is related to enhanced cognitive control.
      Because children are becoming increasingly overweight, unhealthy and unfit,
      understanding the neurocognitive benefits of an active lifestyle during childhood
      has important public health and educational implications.

PMID- 20693804
TI  - Efficacy and safety of pimecrolimus cream 1% in mild-to-moderate chronic hand
      dermatitis: a randomized, double-blind trial.
AB  - BACKGROUND: Chronic hand dermatitis is common and difficult to treat. OBJECTIVE:
      Our aim was to assess the efficacy of pimecrolimus cream 1% in mild-to-moderate
      chronic hand dermatitis. METHODS: Adult patients (n = 652) were randomized to
      pimecrolimus 1% or vehicle cream twice daily with overnight occlusion for 6
      weeks, followed by a 6-week open-label pimecrolimus treatment. Primary efficacy
      was 5-point Investigators' Global Assessment of prospectively selected 'target
      hand' as treatment success (Investigators' Global Assessment 0 or 1) and
      treatment failure. Pruritus relief was also assessed. RESULTS: Following double
      blind phase treatment, target hand treatment success was achieved in 29.8 and
      23.2% of the patients in the pimecrolimus and vehicle groups, respectively (p =
      0.057). The proportion of patients experiencing pruritus relief was significantly
      higher in the pimecrolimus group compared to the vehicle group at all time points
      throughout the double-blind phase. CONCLUSION: The groups were comparable with
      respect to treating disease signs. Pruritus relief, however, was significantly
      greater in the pimecrolimus group.

PMID- 20693805
TI  - Effect of chorionic villus sampling on uterine artery Doppler.
AB  - INTRODUCTION: The aim of this study was to examine the potential effect of
      chorionic villus sampling (CVS) on placental perfusion by examining the change in
      uterine artery pulsatility index (PI) between the first and second trimesters of
      pregnancy. MATERIALS AND METHODS: This was a prospective screening study for
      pregnancy complications which included measurement of uterine artery PI at 11(+0)
      to 13(+6) weeks and at 20(+0) to 24(+6) weeks of gestation. In women at increased
      risk for fetal aneuploidies, CVS was performed. Uterine artery PI in the first
      and second trimesters, and the change in PI between the two examinations were
      compared between the CVS and non-CVS groups. RESULTS: The study population
      included 8,822 singleton pregnancies, in 308 of which CVS was performed. In the
      CVS group, compared to the non-CVS group, the median uterine artery PI before
      CVS, corrected for gestational age, was higher in both the first and second
      trimesters of pregnancy, but the change in PI between the two examinations was
      not significantly different (p = 0.789). CONCLUSION: The performance of CVS in
      the first trimester is unlikely to interfere with normal placentation.

PMID- 20693806
TI  - Maternal thyroid function at 11-13 weeks of gestation in women with
      hypothyroidism treated by thyroxine.
AB  - OBJECTIVE: The aim of this study in pregnant women with hypothyroidism treated by
      levothyroxine is to examine the interrelations between thyroid-stimulating
      hormone (TSH), free thyroxine (FT(4)) and free tri-iodothyronine (FT(3)), and
      examine whether in such patients the treatment is adequate. METHODS: This was a
      retrospective cross-sectional study. Maternal serum concentrations of FT(3),
      FT(4) and TSH were measured at 11-13 weeks in 164 singleton pregnancies from
      women with hypothyroidism before pregnancy receiving treatment with thyroxine.
      The values were compared to the results in 4,318 normal singleton pregnancies.
      RESULTS: In the hypothyroid group, compared to the normal group, there was an
      increase in median TSH (1.990 vs. 1.007 MoM) and FT(4) (1.052 vs. 0.992 MoM) and
      decrease in FT(3) (0.901 vs. 0.991 MoM). Serum FT(4) was at or above the 2.5th
      centile in 158 (96.3%) cases but TSH was above the 97.5th centile in 48 (29.3%)
      and FT(3) was below the 2.5th centile in 49 (29.9%) cases. In both the
      hypothyroid and unaffected groups there were significant associations between TSH
      and FT(4), TSH and FT(3) and between FT(3) and FT(4). CONCLUSIONS: In a high
      proportion of pregnant women with hypothyroidism treated with levothyroxine there
      is evidence of persistent hypothyroidism because the treatment is inadequate in
      correcting the levels of FT(3).

PMID- 20693807
TI  - Etiopathology of Arnold-Chiari malformation: a fetal rat model of dysraphism.
AB  - OBJECTIVES: We report an experimental fetal rat model with the aim of comparing
      two surgical methods used to check Arnold-Chiari Malformation (ACM) by
      dysraphism. We also wanted to (1) determine which type(s) of ACM akin to human
      anatomical findings were generated with the model and (2) study whether a
      cerebrospinal fluid pressure gradient could be responsible for ACM's
      etiopathology. MATERIALS AND METHODS: At E20, a mean of two fetuses per pregnant
      rat underwent an incision at the 2-3 lumbar level, deep into the medulla
      oblongata central canal, by two different surgical methods. Cesarian section was
      performed at E22. Dysraphic fetuses were examined clinically. Those born alive
      and controls without lesions were anatomically and histologically studied.
      RESULTS: Method 2 was better than method 1 at reproducing the model. 100% of
      operated fetuses showed no spontaneous motility or sensibility to pressure on the
      posterior limbs in addition to anatomopathological evidence of type II ACM.
      CONCLUSIONS: A high rate of ACM could be checked by dysraphism with both methods.
      The opening of the central canal was demonstrated to generate a cerebrospinal
      fluid pressure gradient responsible for the herniation of encephalic structures
      comparable with human ACM. We believe this model may be useful for evaluating
      further strategies for prenatal treatment.

PMID- 20693809
TI  - Addition of infliximab to standard therapy for ANCA-associated vasculitis.
AB  - BACKGROUND: Tumour necrosis factor-alpha (TNF) is implicated in the pathogenesis
      of anti-neutrophil cytoplasm antibody-associated vasculitis (AAV). Current
      immunosuppressive therapy is associated with considerable morbidity and
      mortality. Anti-TNF antibody therapy (infliximab) may help control AAV by
      providing more targeted immunosuppression and allow reductions in the use of
      corticosteroids and cyclophosphamide, thereby reducing the burden of
      immunosuppression with its associated morbidity and mortality. METHODS: 33
      patients with active AAV participated in this cohort study. Patients were treated
      with standard therapy (corticosteroids and cyclophosphamide with additional
      plasma exchange in the case of life- or organ-threatening disease) or standard
      therapy + infliximab at weeks 0, 2, 6 and 10. The primary outcome measure was
      time to remission. Other outcome measures were adverse events, cumulative damage
      scores and relapse, as well as biomarkers for circulating activated and
      regulatory T cells. Follow-up was for 12 months. RESULTS: 17 patients received
      standard therapy alone; 16 patients received additional infliximab. The addition
      of infliximab to standard therapy did not influence remission rates, adverse
      events, damage index scores, relapse rates or biomarker levels in this cohort
      study. CONCLUSION: The addition of infliximab to standard therapy did not confer
      clinical benefit for patients with active AAV.

PMID- 20693810
TI  - Effect of single-dose rituximab on primary glomerular diseases.
AB  - BACKGROUND: A paradigm shift from such toxic 'nonspecific' therapies to selective
      immunomodulating regimens is necessary for glomerular diseases. Rituximab, which
      acts by inhibiting CD20-mediated B cell proliferation and differentiation, could
      be effective in the treatment of nephrotic syndrome as shown in recent reports.
      DESIGN: To assess the effects of rituximab in patients with primary glomerular
      diseases, including minimal-change disease, immunoglobulin A (IgA) nephropathy,
      focal segmental glomerulonephritis, membranous nephropathy and
      membranoproliferative glomerulonephritis, we performed a prospective trial of the
      effects of single-dose rituximab therapy in 24 patients. We prospectively
      evaluated the serum and urinary biochemical parameters before and after 6 months
      of therapy. RESULTS: In all of the patients studied, depletion of CD19 and CD20
      cells was noted, with significant reduction in the degree of proteinuria from 3.7
      +/- 3.4 g/day at baseline to 1.3 +/- 2.0 g/day at 6 months after the drug
      administration (p = 0.002). However, no significant changes of the serum
      creatinine, urinary RBC sediment, serum CD4/8 or serum IL-4 levels were observed
      at 6 months after the drug administration. In subjects with IgA nephropathy,
      while depletion of CD19 and CD20 cells was noted, no significant change in the
      severity of proteinuria was observed at 6 months after the drug administration as
      compared with the level at the baseline. CONCLUSION: For the treatment of primary
      glomerular diseases, the use of a single dose of rituximab is demonstrated with
      no serious adverse events. Further study of the mechanism of action of rituximab
      in successfully treated patients could encourage new perspectives in the
      treatment of primary glomerular diseases.

PMID- 20693811
TI  - Still sad after successful renal transplantation: are we failing to recognise
      depression? An audit of depression screening in renal graft recipients.
AB  - BACKGROUND: Depression is common in chronic physical illness, including renal
      graft recipients. There is evidence that depression is an independent marker of
      poorer prognosis in dialysis patients. In the UK, screening is advocated by the
      National Institute for Health and Clinical Excellence guidelines, and validated
      screening tools exist, such as the Beck Depression Inventory (BDI). METHODS: We
      audited our renal graft recipient outpatient clinic to see if screening was being
      undertaken by our clinicians, and to confirm the rates of depressive symptoms in
      our population as reported by the BDI. RESULTS: In a sample of 58 transplant
      patients, we found that the screening rate for depression was poor, particularly
      by nephrologists (n = 8, 13.8%). In addition, 13 (22.4%) of our patients had
      significant depressive symptoms (BDI score >= 16). Following univariate analysis,
      we found that the most important predictor of current significant depressive
      symptoms was a past history of depression. CONCLUSIONS: Despite the limitations
      of our small audit, our results confirm that depression is under-screened in
      renal graft recipients, even in those with a known history of depression. We
      recommend increased awareness of depression and implementation of regular
      screening in an outpatient setting; in this regard, the BDI may have utility.

PMID- 20693812
TI  - Low iPTH can predict vascular and coronary calcifications in patients undergoing
      peritoneal dialysis.
AB  - BACKGROUND: There is substantial evidence that low levels of serum intact
      parathyroid hormone (iPTH) are associated with vascular calcium deposition and
      subsequent increased cardiovascular risk in chronic kidney disease patients. The
      purpose of this study was to determine the relationship between the serum iPTH
      level, and vascular and coronary artery calcifications (VCs, CACs) and arterial
      stiffness in peritoneal dialysis (PD) patients. METHODS: In this cross-sectional
      study, 93 PD patients were included. VCs, CACs and arterial stiffness were
      measured by simple X-rays of the hands and pelvis, multi-slice coronary CT and
      brachial-ankle pulse wave velocity (BaPWV). RESULTS: Patients were divided into 3
      groups according to iPTH levels. The prevalence of severe VCs (VC score >= 3) was
      highest in the low iPTH group (<150 pg/ml). In multivariate analysis, the
      presence of diabetes mellitus and a low iPTH were shown to be significant risk
      factors for severe VCs. In addition, a simple VC score of >= 1 was a significant
      variable for predicting severe CACs (CAC score >= 400). CONCLUSION: Low iPTH and
      the presence of diabetes mellitus are thought to be independent risk factors for
      predicting VCs. VCs determined by simple X-ray can further predict the
      coexistence of CACs that ultimately might contribute to increased cardiovascular
      risk in PD patients.

PMID- 20693813
TI  - Role of the parathyroid gland vascularization index in predicting percutaneous
      ethanol injection efficacy in refractory uremic hyperparathyroidism.
AB  - AIMS: To evaluate the role of the quantitative vascularization index (VI) as a
      measure of the completeness of percutaneous ethanol injection therapy (PEIT).
      METHODS: A total of 37 dialysis patients with secondary hyperparathyroidism
      refractory to medical therapy received PEIT. We analyzed the role of a
      quantitative marker of parathyroid adenoma activity, i.e. VI, flow index and
      vascular flow index as measured by 3-dimensional Doppler ultrasound with a 3
      dimensional histogram software, for all patients before treatment and at 1 month
      and 6 months after PEIT. RESULTS: Serum intact parathyroid hormone (i-PTH) level
      showed a strong positive correlation with the VI both before (p < 0.001) and
      after (p < 0.001) PEIT. There was no correlation between i-PTH level and the
      volume of the gland either before (p = 0.697) or after (p = 0.564) PEIT. One
      month after PEIT, 20 patients (group 1) reached the target of i-PTH <= 300 pg/ml
      and 17 patients (group 2) did not. Group 2 patients had significantly greater VI
      and i-PTH prior to PEIT than group 1 patients (42.23 +/- 8.38 vs. 14.95 +/- 8.07,
      p <0.001 and 1,447 +/- 243 vs. 859 +/- 231, p < 0.001 respectively). CONCLUSION:
      A higher VI indicates a higher i-PTH, and the VI may be a reliable predictor of
      the completeness of PEIT.

PMID- 20693814
TI  - Prevalence and management of anaemia in renal transplant recipients: data from
      ten European centres.
AB  - BACKGROUND: Although it is a known predictor of mortality, there is a relative
      lack of recent information about anaemia in kidney transplant recipients. Thus,
      we now report data about the prevalence and management of post-transplant anaemia
      (PTA) in Europe 5 years after the TRansplant European Survey on Anemia Management
      (TRESAM) study. METHODS: In a cross-sectional study enrolling the largest number
      of patients to date, data were obtained from 5,834 patients followed at 10
      outpatient transplant clinics in four European countries using the American
      Society of Transplantation anaemia guideline. RESULTS: More than one third (42%)
      of the patients were anaemic. The haemoglobin (Hb) concentration was
      significantly correlated with the estimated glomerular filtration rate (eGFR) (r
      = 0.4, p < 0.001). In multivariate analysis, eGFR, serum ferritin, age, gender,
      time since transplantation and centres were independently and significantly
      associated with Hb. Only 24% of the patients who had a Hb concentration <110 g/l
      were treated with an erythropoiesis-stimulating agent. The prevalence of anaemia
      and also the use of erythropoiesis-stimulating agents were significantly
      different across the different centres, suggesting substantial practice
      variations. CONCLUSIONS: PTA is still common and under-treated. The prevalence
      and management of PTA have not changed substantially since the TRESAM survey.

PMID- 20693815
TI  - The Sask formula to estimate glomerular filtration rate in renal transplant
      patients.
AB  - The aim of this study was to develop a glomerular filtration rate (GFR) equation
      for renal transplant and compare its performance with Chronic Kidney Disease
      Epidemiology Collaboration (CKD-EPI) and isotope dilution mass spectrometry
      (IDMS) equations. Using genetic symbolic regression analysis, the Sask equation
      was developed from a training sample of 772 isotope GFR (iGFR) scans performed in
      99 transplanted patients. It was then validated in two other samples of 269 scans
      with the same number of patients. Standard methods including accuracy at 30%
      range from reference values were compared. In two validation samples, the Sask
      equation maintained the lowest bias of -0.7 +/- 19.0 and 0.4 +/- 18.4 ml/min/1.73
      m(2) (p < 0.05) versus -3.1 +/- 19.6 and -7.2 +/- 18.8 ml/min/1.73 m(2) for CKD
      EPI and -2.2 +/- 19.2 and -6.5 +/- 18.3 ml/min/1.73 m(2) for IDMS, respectively.
      In those with iGFR between 90 and 30 ml/min/1.73 m(2), the Sask equation
      demonstrated: (1) the lowest bias of -1.0 +/- 15.7 and -0.4 +/- 15.7 ml/min/1.73
      m(2) (p < 0.05 vs. other tests); (2) an accuracy of 75.5 and 76.1% (p < 0.05 vs.
      other tests), and (3) a mean percentage error of 1.9 +/- 30.5 and -4.1 +/- 31.4
      ml/min/1.73 m(2) (p < 0.05 vs. other tests). Analysis based on gender
      demonstrated improved performance in the total and subtotal female populations
      with GFR between 90 and 30 ml/min/1.73 m(2). The CKD-EPI and Sask equations
      performed better than IDMS. The Sask equation demonstrated improved bias over CKD
      EPI, with iGFR between 90 and 30 ml/min/1.73 m(2), particularly in females.

PMID- 20693816
TI  - Differential expression of renal proteins in a rodent model of Meckel syndrome.
AB  - BACKGROUND: Meckel syndrome (MKS) is a fatal autosomal recessive condition with
      prominent renal cystic pathology. Renal protein misexpression was evaluated in
      the Wpk rat model of human MKS3 gene disease to identify biomarkers for the
      staging of renal cystic progression. METHODS: Misexpressed proteins were compared
      between early and late stages of MKS renal cystic disease using proteomic
      analysis (two-dimensional gel electrophoresis with LC-MS/MS identification)
      followed by Western blot analysis. RESULTS: A proteomic analysis identified 76
      proteins with statistically different, normalized abundance in at least one
      group. Subsequently, Western blot was used to confirm differential expression in
      several of these and polycystic kidney disease (PKD)-associated proteins.
      Galectin-1 and vimentin were identified as overexpressed proteins, which have
      been previously found in the jck mouse model of nephronophthisis 9. Ciliopathic
      PKD proteins, polycystins 1 & 2, and fibrocystin were also differentially
      expressed in Wpk kidney. CONCLUSION: In the Wpk rat, misexpressed proteins were
      identified that were also implicated in other forms of cystic disease. Numerous
      proteins were either over- or underexpressed in late-stage disease. Differences
      in protein expression may serve as biomarkers of cystic disease and its
      progression.

PMID- 20693817
TI  - Intravitreal triamcinolone.
AB  - BACKGROUND: to provide an update on the intravitreal use of triamcinolone
      acetonide. METHODS: Review of literature regarding triamcinolone-related
      research. RESULTS: after the introduction of bevacizumab and ranibizumab into
      clinical practice, intravitreal triamcinolone has lost its leading position as
      the drug most often injected intravitreally. Due to its properties as a long
      acting steroid, triamcinolone has still been used for various conditions such as
      diffuse diabetic macular edema, retinal vein occlusions, pseudophakic cystoid
      macular edema, chronic prephthisical ocular hypotony and uveitis, and in
      combination with bevacizumab or ranibizumab. The complications of intravitreal
      triamcinolone therapy include secondary ocular hypertension in about 40% of the
      eyes injected, cataract and postoperative infectious or noninfectious
      endophthalmitis. CONCLUSIONS: due to its widespread biological effects as a
      steroid and due to a relatively large therapeutic window, intravitreal
      triamcinolone has remained in clinical use for a variety of intraocular
      disorders, and it may be a promising candidate for intravitreal medical
      combination therapies.

PMID- 20693818
TI  - Ocular manifestations of late-onset behcet disease.
AB  - PURPOSE: to describe the demographic characteristics and ocular manifestations of
      patients with late-onset Behcet disease (BD). PATIENTS AND METHODS: The patients
      for this retrospective study were selected using the data obtained from the
      medical records of 16 patients with late-onset BD between January 2000 and May
      2008. RESULTS: twelve (75%) of the cases were male and 4 (25%) were female. The
      mean age of patients was 53.8 +/- 2.9 years (range, 51-60 years). The mean follow
      up period was 4.3 +/- 1.1 years (range, 3-8 years). Throughout the follow-up
      period, panuveitis, posterior uveitis, and anterior uveitis were detected in 11
      (68.7%), 4 (25%) and 1 (6.2%) of 16 patients, respectively. CONCLUSION: in our
      series, the most frequent type of uveitis was panuveitis and male sex seems to be
      a significant risk factor for developing panuveitis. Late-onset BD showed a
      marked preponderance of males with a sex ratio of 3:1.

PMID- 20693819
TI  - Comparison of central retinal thickness in healthy children and adults measured
      with the Heidelberg Spectralis OCT and the zeiss Stratus OCT 3.
AB  - BACKGROUND/AIMS: to compare retinal thickness measurements obtained by the
      Spectralis and Stratus OCT 3 in healthy children and adults. METHODS: central
      volume scan (25-scan pattern) and macular thickness map protocols were performed
      subsequently using the Spectralis OCT and Stratus OCT 3 on a randomly selected
      eye of 34 healthy adults (18-50 years) and 20 children (6-17 years). Nine Early
      Treatment Diabetic Retinopathy Study (ETDRS) subfields were analyzed and compared
      between the children and adults. RESULTS: All retinal thickness measurements
      obtained by the Spectralis OCT were greater than those measured with the Stratus
      OCT 3 (p < 0.01). In adults, the mean paired difference of measurements with both
      devices was 64.9 +/- 13.2 microm (central minimum) and 75.8 +/- 4.7 MUm (central
      subfield). In children, the respective values were 56.6 +/- 13.1 microm and 69.7
      +/- 9.1 microm, being significantly lower (p < 0.05). CONCLUSION: in healthy
      eyes, measurements with the Stratus OCT 3 can be adjusted to measurements
      obtained using the Spectralis OCT by the values mentioned above, considering
      differences between children and adults.

PMID- 20693820
TI  - Results of one-year follow-up examinations after intravitreal bevacizumab
      administration for chronic central serous chorioretinopathy.
AB  - BACKGROUND: our purpose was to report the results of 1-year follow-up
      examinations after intravitreal bevacizumab injection for the treatment of
      chronic central serous chorioretinopathy (CSC). METHODS: five eyes in 5 patients
      with chronic CSC were intravitreally injected with 1.25 mg/0.05 ml of
      bevacizumab. The need for retreatment was evaluated if spectral-domain optical
      coherence tomography showed the presence of subretinal fluid at the time of a 1
      month follow-up examination. Best-corrected visual acuity and central foveal
      thickness were compared between baseline and 1 year after the first injection.
      RESULTS: the mean logarithm of the minimum angle of resolution (logMAR) best
      corrected visual acuity improved from 0.23 +/- 0.46 to 0.17 +/- 0.47 and the mean
      central foveal thickness significantly decreased from 323 +/- 98 microm to 171 +/
      63 microm (p < 0.05). CONCLUSION: The intravitreal injection of bevacizumab is
      well tolerated in maintaining vision and reducing serous retinal detachment in
      patients with chronic CSC, as evaluated at a 1-year follow-up examination.

PMID- 20693821
TI  - Radial optic neurotomy in central retinal vein occlusion does not influence
      ocular hemodynamics.
AB  - PURPOSE: radial optic neurotomy (RON) is used for the treatment of central
      retinal vein occlusion. Its effects on visual acuity differ substantially between
      patients. Our study aims to evaluate if RON has an impact on ocular
      microcirculation and if analysis of ocular microcirculation might serve as a
      predictor for surgical success. PROCEDURES: a complete ophthalmologic examination
      including color Doppler imaging of the retrobulbar vessels was performed before
      and 2-4 months after RON in 12 patients. RESULTS: mean visual acuity was 0.09 +/-
      0.03 prior to and 0.24 +/- 0.12 after RON. Visual acuity improved in 7 (+3.5 +/-
      0.9 lines), was stable in 3 (+/- 0 lines) and worsened in 2 cases (-6 and -2
      lines). Doppler parameters were not affected by RON, and no correlations between
      visual acuity and perfusion parameters were found. CONCLUSIONS: Our data indicate
      that RON does not influence ocular microcirculation. None of the assessed
      hemodynamic parameters appears to be a predictor for surgical success.

PMID- 20693823
TI  - Imaging studies in metastatic urogenital cancer patients undergoing systemic
      therapy: recommendations of a multidisciplinary consensus meeting of the
      Association of Urological Oncology of the German Cancer Society.
AB  - INTRODUCTION: Imaging studies are an integral and important diagnostic modality
      to stage, to monitor and follow-up patients with metastatic urogenital cancer.
      The currently available guidelines on diagnosis and treatment of urogenital
      cancer do not provide the clinician with evidence-based recommendations for daily
      practice. OBJECTIVES: To develop scientifically valid recommendations with regard
      to the most appropriate imaging technique and the most useful time interval in
      metastatic urogenital cancer patients undergoing systemic therapy. METHODS: A
      systematic literature review was performed searching MedLine, Embase and Web of
      Science databases using the terms prostate, renal cell, bladder and testis cancer
      in combination with the variables lymph node, lung, liver, bone metastases,
      chemotherapy and molecular therapy, and the search terms computed tomography,
      magnetic resonance imaging and positron emission tomography were applied. A total
      of 11,834 records were retrieved from all databases. The panel reviewed the
      records to identify articles with the highest level of evidence using the
      recommendation of the US Agency for Health Care Policy and Research. CONCLUSIONS:
      Contrast-enhanced computed tomography remains the standard imaging technique for
      monitoring of pulmonary, hepatic and lymph node metastases. Bone scintigraphy is
      still the most widely used imaging technique for the detection and follow-up of
      osseous lesions. For clinical trials it might be replaced by either PET-CT or MRI
      of the skeletal axis. Response assessment for patients treated with cytotoxic
      regime is best performed by the RECIST/WHO criteria; treatment response to
      molecular triggered therapy is best assessed by CT evaluating decrease in tumor
      size and density. Cross-sectional imaging studies for response assessment might
      be obtained after each 2 cycles of systemic therapy to early stratify responders
      from non-responders.

PMID- 20693822
TI  - G protein-coupled receptor-associated sorting protein 1 regulates the
      postendocytic sorting of seven-transmembrane-spanning G protein-coupled
      receptors.
AB  - The largest superfamily of membrane proteins that translate extracellular signals
      into intracellular messages are the 7-transmembrane-spanning (7TM) G protein
      coupled receptors (GPCR). One of the ways in which their activity is controlled
      is by the process of desensitization and endocytosis, whereby agonist-activated
      receptors are rapidly and often reversibly silenced through removal from the cell
      surface. Indeed, following endocytosis, individual receptors can be sorted
      differentially between recycling endosomes and lysosomes, which controls the
      reversibility of the silencing. Thus, endocytosis can either serve as a mechanism
      for receptor resensitization by delivering receptors back to the plasma membrane
      or facilitate receptor downregulation by serving as the first step towards
      targeting the receptors to lysosomes for degradation. The sorting of receptors to
      the lysosomal pathway can be facilitated by interaction with an array of
      accessory proteins. One of these proteins is the GPCR-associated sorting protein
      1 (GASP-1), which specifically targets several 7TM-GPCR to the lysosomal pathway
      after endocytosis. Furthermore, GASP-1 was recently found to directly affect the
      signaling capacity of a 7TM-GPCR. Importantly, the in vivo relevance of GASP-1
      dependent receptor sorting has also begun to be verified in animal models. Here,
      we summarize the recent advances in elucidating GASP-1-dependent receptor sorting
      functions and their potential implications in vivo.

PMID- 20693824
TI  - Impact of lymph node invasion and sarcomatoid differentiation on the survival of
      patients with locally advanced renal cell carcinoma.
AB  - INTRODUCTION: The application of current prognosticators in locally advanced
      nonmetastatic renal cell carcinoma (RCC) is controversial. We analyzed the impact
      of clinical and pathological variables on the survival of this subset of
      patients. PATIENTS AND METHODS: We studied patients with RCC in stages III and IV
      without metastases, treated surgically between 1980 and 2009. We calculated
      disease-free (DFS) and cancer-specific survival (CSS), and the relation of
      clinical and pathological variables with these end-points. RESULTS: We identified
      126 patients with locally advanced RCC; 8.7% had sarcomatoid differentiation.
      Tumor stage was pT3a in 48% and pT3b in 42%; 11.9% had lymph node invasion (N+).
      Patients with N- and N+ had a 10-year DFS of 49.0 and 23.4%, respectively (p =
      0.0001). In multivariate analysis N+ (p = 0.0002) was the strongest predictor of
      DFS. The 10-year CSS of patients without sarcomatoid differentiation was 53.1%
      while those with sarcomatoid differentiation did not reach the median time to
      death (p < 0.0001). In multivariate analysis, sarcomatoid differentiation (p =
      0.01) was the strongest predictor of CSS. CONCLUSIONS: Locally advanced RCC
      portends poor prognosis. Preoperatively, weight loss and Eastern Cooperative
      Oncology Group performance status are predictors of recurrence and mortality,
      respectively. However, the most powerful predictors of DFS and CSS in our cohort
      were lymph node status and sarcomatoid differentiation.

PMID- 20693825
TI  - Influence of visceral obesity on oncologic outcome in patients with renal cell
      carcinoma.
AB  - OBJECTIVE: At present, computed tomography (CT) is used in almost all patients
      with renal tumors. We aimed to investigate the relationship between visceral
      adipose tissue (VAT), as assessed by CT, and various other factors in patients
      with renal cell carcinoma (RCC). METHODS: We undertook an examination of VAT in
      117 male patients undergoing nephrectomy or partial nephrectomy at Chiba
      University Hospital using software designed to detect VAT in the horizontal plane
      of the body cavity. Pathological stage, microvascular invasion, tumor grade,
      performance status, C-reactive protein, BMI, hypertension, hyperlipemia,
      hyperglycemia, history of smoking and cause-specific survival rate were examined
      in relation to VAT, and multivariate Cox regression analysis was used to
      determine significant predictors of cause-specific survival. RESULTS: VAT in
      patients with stage I disease was significantly greater than that in patients
      with more advanced disease (p = 0.0219). VAT in patients with microvascular
      invasion was significantly smaller than in those without microvascular invasion
      (p = 0.0260). Patients with high VAT had significantly higher cumulative cause
      specific survival when compared to patients with low VAT (p = 0.0257).
      CONCLUSION: VAT was associated with better clinical features in patients with
      RCC. Further study is necessary in order to clarify the role of VAT in RCC.

PMID- 20693826
TI  - Linking global citizenship, undergraduate nursing education, and professional
      nursing: curricular innovation in the 21st century.
AB  - As we move into the 21st century, our roles as nurses are becoming more complex.
      Inequities in health within and across nations demand that nursing students
      examine the interconnectedness between local and global health challenges and
      contribute to the development and implementation of solutions to these
      challenges. In this article, we examine concepts related to global citizenship,
      globalization, social responsibility, and professionalism and link them to
      curricular innovation in nursing education. We argue that the development of
      global citizenship is a fundamental goal for all nursing students and that to
      achieve this, nurse educators must move beyond the creation of international
      placement opportunities or the use of global examples within existing courses.
      Nurse educators must develop strategies and design innovative curricula to
      provide opportunities for all students to become engaged with the concept of
      global citizenship and the role of nurses in a global world.

PMID- 20693827
TI  - Social justice: hearing voices of marginalized girls expressed in theatre
      performance.
AB  - In this article we describe a research project studying the strengths of
      adolescent girls in an open custody treatment group home. Although the literature
      is replete with research about the deficits of girls in conflict with the law,
      their strengths are poorly understood and seldom researched. Understanding these
      girls' strengths fulfills a nursing mandate to foster social justice by
      challenging the status quo of the prevailing social order. A theatre performance
      of the research findings resulted in a profound audience impact. Arts-based
      research and participatory action research offer new ways of accessing
      marginalized populations' strengths and challenging harmful societal assumptions.

PMID- 20693828
TI  - Silence, stigma, and shame: a postmodern analysis of distress during menopause.
AB  - Because of the complexity of a midlife woman's life and the variation of the
      manifested symptoms of menopause, much remains inconclusive regarding the
      experience of distress during the menopause transition. The purpose of this
      narrative analysis study was to examine experiences of distress during the
      menopause transition using a postmodern feminist framework. Findings include
      experiences of shame related to symptom experience and prevailing social
      discourses on menopause and aging. Clinicians must be cautioned of the potential
      for silencing and withdrawal in women who may not be receiving adequate support,
      and must advocate for more choices for midlife women.

PMID- 20693830
TI  - The advocate-analyst dialectic in critical and postcolonial feminist research:
      reconciling tensions around scientific integrity.
AB  - With increased attentiveness to social justice and the social and economic
      inequities that shape health, well-being, and health care access, nurse
      researchers, particularly those positioning their work as emancipatory, negotiate
      the dialectic of analysis and advocacy. Drawing on postcolonial feminism, we
      explore this dialectic and associated ramifications for scientific integrity.
      Staying true to critical foundations shifts the focus from advocacy as "speaking
      on behalf of" to rigorous reflexive analysis that decenters dominant discourses
      to open up the possibility for those who have been marginalized to exercise human
      agency and work alongside researchers toward social justice for all.

PMID- 20693831
TI  - Policy talk: gender and the regulation of nursing knowledges and practices.
AB  - This article discusses findings from a qualitative policy study using comparative
      life history methodology with 10 Canadian female nurses who were lesbian health
      advocates. A critical gender lens was used to examine policy literature and to
      frame an analysis of how nurses experienced and understood their engagement with
      policy by focusing on their "policy talk." The findings suggest that nurses
      participate in policy processes in multiple ways through their everyday political
      work, but their practice is contested and contextualized by tensions between
      dominant and counter discourses of policy. Complex gendered social relations
      structure diverse nurses' lives as policy actors and regulate nurses' knowledges
      and practices.

PMID- 20693832
TI  - Rethinking biopower: posthumanism, bare life, and emancipatory work.
AB  - This article answers a call, recently published in Advances in Nursing Science,
      to more fully explore the use of Italian political philosopher Giorgio Agamben's
      theory of biopower in nursing research and scholarship. Giorgio Agamben argues
      that biopower is not a modern phenomenon, and critical analysis of the historical
      origins of Western political practice shows how humanist discourse has been
      complicit in a long tradition of marginalization and violence, accomplished in
      each era by designating certain classes of human beings as "bare life." I discuss
      how I have used Agamben's theory to frame my own research, and the challenges of
      applying this theory in emancipatory work.

PMID- 20693833
TI  - Addressing whiteness in nursing education: the sociopolitical climate project at
      the University of Washington School of Nursing.
AB  - This article describes a project designed to change the climate of whiteness in
      academic nursing. Using an emancipatory, antiracist perspective from whiteness
      studies, we describe a project that helped faculty and staff to work together to
      challenge and begin to change the status quo of unnamed white privilege and
      racial injustice in nursing education.

PMID- 20693834
TI  - Interpretation: a political and social practice.
AB  - The purpose of this article was to illustrate that interpretation is a political
      and social practice and to explore the conceptualization of interpretation as a
      political and social practice within the discipline of nursing. A critical view
      of language, meaning, and interpretation reveals that words are influenced by
      sociopolitical context and empiricism is engulfed in interpretations derived from
      the environment. The deliberations reveal that how we perceive our nature of
      being in the world affects our interpretations. In contrast, from a critical
      theory lens the discussion reveals that interpretation becomes a process of
      penetration of different contexts and of an evolutionary praxis effecting
      transformation.

PMID- 20693835
TI  - Positron emission tomography with 18F-fluorodeoxyglucose is a useful tool for the
      diagnosis of pheochromocytomas without distant metastasis, where malignancy is
      suspected on the basis of histopathologic analysis.
AB  - A 69-year-old woman, who had been undergoing treatment for hypertension, was
      admitted to the hospital for the evaluation of a tumor in the right adrenal gland
      and of episodic hypertension. She was diagnosed with pheochromocytoma on the
      basis of elevated urine catecholamine and metabolite concentrations and positron
      emission tomography (PET) results; however, the results of I
      metaiodobenzylguanidine (I-MIBG) scintigraphy were negative. The patient
      underwent laparoscopic right adrenalectomy. Malignancy was suspected on the basis
      of histopathologic studies. After surgery, the elevated catecholamine and
      metabolite concentrations and the blood pressure returned to normal; furthermore,
      the symptoms, including severe headache, reduced. The authors report a case of
      pheochromocytoma that was suspected to be malignant on the basis of
      histopathologic analysis and was detected by F-fluorodeoxyglucose (FDG)-PET but
      not by MIBG. Thus, FDG-PET may be a prognostic marker for malignant
      pheochromocytomas with or without metastasis.

PMID- 20693836
TI  - Successful treatment of a locally invasive cryptococcoma mimicking primary
      thyroid cancer with fluconazole.
AB  - A patient with no immune compromise and no constitutional or pulmonary symptoms
      presented with an enlarging neck mass abutting the thyroid gland and extending
      through the pleura into the lung. Microbiologic evaluation revealed a diagnosis
      of cryptococcoma, and the patient responded well to oral fluconazole therapy. To
      the authors' knowledge, this is the first case describing a locally invasive
      cryptococcoma mimicking a primary thyroid malignancy in the absence of systemic
      symptoms.

PMID- 20693837
TI  - Recent advances: adjuvant therapy for older women with breast cancer.
AB  - The U.S. population is now healthier and more long-lived than ever, and the
      average life expectancy for a woman born today is about 80 years. An elderly
      woman's life expectancy, which is related to comorbidity and functional status,
      is particularly important when determining the appropriate choice of adjuvant
      chemotherapy and endocrine therapy. In addition, the disease stage and the
      tumor's biologic characteristics (grade and hormone/human epidermal growth factor
      [HER]-2 receptor status) must be considered when formulating a treatment plan for
      3 clinically distinctive breast cancer subgroups: (1) hormone receptor negative
      (HR-) and HER-2 negative ("triple-negative" tumors, about 15% of older patients);
      (2) hormone receptor positive (HR+) and HER-2 negative (the largest group
      comprising about 70% of older patients); and (3) HER-2 positive irrespective of
      HR status (about 15% of older patients). The functional status of an older woman
      can be estimated by a Comprehensive Geriatric Assessment (CGA). A traditional CGA
      is time consuming, but testing of shorter, validated CGA instruments is ongoing.
      Monitoring toxicity in the elderly is especially important because even low-grade
      toxicity can have a significant effect on function. Eligible older women should
      be considered for state-of-the-art treatment, including clinical trials to
      determine the optimal adjuvant regimens for this patient population and how the
      therapies affect the woman's functioning and quality of life.

PMID- 20693838
TI  - From the guest editor: introduction for immunotherapy of cancer.

PMID- 20693839
TI  - Chemoimmunotherapy.
AB  - Cancer chemotherapy drugs are historically regarded as detrimental to immunity
      because of their myelosuppressive effects. However, accumulating data suggest
      that the antitumor activity of conventional cancer chemotherapy results in part
      from its ability to harness the innate and adaptive immune systems by inducing
      immunologically active tumor cell death. Additional data broaden the immunologic
      effect of cancer chemotherapy drugs, demonstrating that some drugs have the
      ability to disrupt pathways of immune suppression and immune tolerance in a
      manner that depends on the drug dose, and the timing of its administration in
      relation to immunotherapy. Understanding the cellular and molecular basis of the
      interactions between chemotherapy drugs and the immune system will facilitate the
      strategic development of chemoimmunotherapy treatment regimens that both maximize
      tumor regression and the antitumor immune response for the long-term clinical
      benefit of cancer patients.

PMID- 20693840
TI  - Cellular vaccine approaches.
AB  - Therapeutic cancer vaccines aim to generate immunologic targeting of cancer cells
      through the induction of effective cellular and antibody-mediated responses
      specific for antigens selectively expressed by the tumor. Exploiting the adaptive
      immune system as a targeted tool against cancer is appealing in its capacity for
      exact specificity and avoidance of unintended tissue damage seen by other
      conventional agents such as chemotherapy. There are a multitude of challenges to
      designing effective vaccine strategies. The components of a vaccine strategy
      start with the challenges of selecting immunogenic, tumor-specific antigen
      targets, choosing a platform with which to deliver the antigens, and enhancing
      the immunostimulatory context in which the vaccines are delivered. Although
      understanding the components of effective T-cell activation is essential,
      successful effector T cells can only be produced if there is also an
      understanding of the natural processes that tumors exploit to down-modulate
      active immune responses. These processes are normally used to down-regulate
      excessive tissue-destructive immune responses against infectious agents once the
      infecting agent is cleared or to prevent autoimmunity. Advances in molecular and
      cellular technologies continue to provide insights into the regulation of immune
      responses both to infectious agents and to cancer that may be manipulated to tip
      the balance in favor of tumor regression over immune tolerance. This review
      focuses primarily on cellular vaccines. For the purpose of this review, cellular
      vaccines are defined as vaccines that use whole cells or cell lysates either as
      the source of antigens or the platform in which to deliver the antigens.
      Dendritic cell (DC)-based vaccines focus on ex vivo antigen delivery to DCs.
      Other platforms such as GVAX (tumor cells genetically engineered to produce
      granulocyte-macrophage colony-stimulating factor) aim to deliver tumor antigens
      in vivo in an immune stimulatory context to endogenous DCs. Because data continue
      to emerge regarding the importance of the maturation status of DCs and the
      importance of the particular subset of DCs being targeted, these insights will be
      integrated into vaccine strategies that are likely to produce more effective
      vaccines.

PMID- 20693841
TI  - Immune regulatory antibodies: are they the next advance?
AB  - During the past decade, new insights into the mechanisms by which T-cell
      activation and proliferation are regulated have led to the identification of
      checkpoint proteins that either up- or down-modulate T-cell reactivity. In the
      presence of active malignancy, pathophysiologic inhibition of T-cell activity may
      predominate over stimulation. A number of antibodies have been generated that can
      block inhibitory checkpoint proteins or promote the activity of activating
      molecules. In murine models, their use alone or with a vaccine strategy has
      resulted in regression of poorly immunogenic tumors and cures of established
      tumors. The prototypical immune regulatory antibodies are those directed against
      cytotoxic T-lymphocyte antigen-4, a molecule present on activated T cells. In
      this review, the preclinical rationale and clinical experience with 2
      anticytotoxic T-lymphocyte antigen-4 antibodies are extensively discussed,
      demonstrating that abrogation of an immune inhibitory molecule can result in
      significant regression of tumors and long-lasting responses. The unique kinetics
      of antitumor response and the characteristic immune-related side effects of
      ipilimumab are also discussed. This clinical efficacy of this promising antitumor
      agent has been evaluated in 2 randomized phase III trials, whose results are
      eagerly awaited. Programmed death (PD)-1 is another immune inhibitory molecule
      against which an abrogating human antibody has been prepared. Initial preclinical
      testing with anti-PD-1 and anti-PD-L1 has shown encouraging results. Stimulatory
      molecules such as CD40, 41-BB, and OX-40 are also targets for antibody binding
      and activation, not blockade, and early dose ranging trials with antibodies
      against all 3 have shown that they can mediate regression of tumors, albeit with
      their own spectrum of side effects that are different from those that occur with
      abrogation of immune inhibition.

PMID- 20693843
TI  - Chemokines: can effector cells be redirected to the site of the tumor?
AB  - Chemokines (ie, chemoattractant cytokines) are a family of small secreted
      molecules that mediate leukocyte migration. It is becoming increasingly more
      evident that chemokines play an integral role in the initiation of a specific
      immune response. With respect to cancer, chemokines are being studied for both
      their role in tumor biology and as promising immunotherapy candidates. We review
      several areas of chemokine importance in tumor immunity and discuss the
      experimental evidence that is leading to the clinical use of this cytokine family
      in new treatment approaches for patients with cancer.

PMID- 20693844
TI  - Adoptive cell therapy: genetic modification to redirect effector cell
      specificity.
AB  - Building on the principals that the adoptive transfer of T cells can lead to the
      regression of established tumors in humans, investigators are now further
      manipulating these cells using genetic engineering. Two decades of human gene
      transfer experiments have resulted in the translation of laboratory technology
      into robust clinical applications. The purpose of this review is to give the
      reader an introduction to the 2 major approaches being developed to redirect
      effector T-cell specificity. Primary human T cells can be engineered to express
      exogenous T-cell receptors or chimeric antigen receptors directed against
      multiple human tumor antigens. Initial clinical trial results have demonstrated
      that both T-cell receptor- and chimeric antigen receptor-engineered T cells can
      be administered to cancer patients and mediate tumor regression.

PMID- 20693842
TI  - Dendritic cells: are they clinically relevant?
AB  - Cancer vaccines have undergone a renaissance because of recent clinical trials
      showing promising immunologic data and some clinical benefit to patients. Current
      trials exploiting dendritic cells (DCs) as vaccines have shown durable tumor
      regressions in a fraction of patients. Clinical efficacy of current vaccines is
      hampered by myeloid-derived suppressor cells, inflammatory type 2 T cells, and
      regulatory T cells, all of which prevent the generation of effector cells. To
      improve the clinical efficacy of DC vaccines, we need to design novel and
      improved strategies that can boost adaptive immunity to cancer, help overcome
      regulatory T cells and allow the breakdown of the immunosuppressive tumor
      microenvironment. This can be achieved by exploiting the fast increasing
      knowledge about the DC system, including the existence of distinct DC subsets.
      Critical to the design of better vaccines is the concept of distinct DC subsets
      and distinct DC activation pathways, all contributing to the generation of unique
      adaptive immune responses. Such novel DC vaccines will be used as monotherapy in
      patients with resected disease and in combination with antibodies and/or drugs
      targeting suppressor pathways and modulation of the tumor environment in patients
      with metastatic disease.

PMID- 20693845
TI  - Regulatory T cells: overcoming suppression of T-cell immunity.
AB  - Regulatory T cells inhibit cellular immunity and represent an obstacle for the
      development of cancer immunotherapy. The understanding of Treg cellular biology
      has exponentially increased during the last 10 years, driven primarily by elegant
      in vivo studies of mouse models systems and in vitro studies of human cells.
      Numerous clinical strategies are under active investigation to achieve Treg
      depletion or inhibition in patients with cancer, including low-dose
      cyclophosphamide and interleukin-2 or anti-interleukin-2R immunotoxins. To date,
      only modest results have been reported in patients. Our preliminary data suggest
      that the antihuman CD25 monoclonal daclizumab may be useful as an alternative
      approach for in vivo Treg depletion, but the mechanism of action of this effect
      remains to be elucidated. Certain immune modulatory agents may indirectly affect
      Tregs in patients with cancer but not necessarily in the desired direction for
      the therapeutic setting. More sophisticated techniques that have become available
      for Treg analysis in patients will assist in this important translational effort.

PMID- 20693846
TI  - Myeloid-derived suppressor cells in human cancer.
AB  - Myeloid-derived suppressor cells are one of the major factors responsible for
      immune suppression in cancer. They also contribute to limited efficacy of current
      vaccination strategies. Here, we give an overview of the myeloid-derived
      suppressor cells field focusing primarily on the studies in cancer patients and
      current and future therapeutic options targeting these cells.

PMID- 20693847
TI  - Indoleamine 2,3-dioxygenase: is it an immune suppressor?
AB  - This article covers what is currently known about the role of the enzyme
      indoleamine 2,3-dioxygenase (IDO) in cancer-related immunosuppression and the
      clinical research on IDO inhibitors. A PUBMED search was performed using the
      terms IDO, indoleamine 2,3-dioxygenase, 1-MT. IDO is an inducible enzyme that
      catalyzes the rate-limiting first step in tryptophan catabolism. This enzyme is
      overexpressed in response to IFNgamma in a variety of different malignancies. IDO
      causes immunosuppression through breakdown of tryptophan in the tumor
      microenvironment and tumor-draining lymph nodes. The depletion of tryptophan and
      toxic catabolites renders effector T cells inactive and dendritic cells
      immunosuppressive. Preclinical data suggest that IDO inhibition can delay tumor
      growth, enhance dendritic cell vaccines, and synergize with chemotherapy through
      immune-mediated mechanisms. The lead IDO inhibitor, d-1-methyl-tryptophan (d-1
      MT), was selected for phase I trials and seems to have immune modulating
      activity. Subsequently, another isoform of IDO, IDO2, was discovered and found to
      be the target of d-1-MT. Multiple single-nucleotide polymorphisms in IDO2
      affecting its catalytic activity may serve as a pharmacogenetic predictive
      biomarker for d-1-MT. The IDO pathway is an important mechanism of tumor-related
      immunosuppression and blocking it could improve cancer immunotherapy outcomes.
      Clinical development of d-1-MT and other IDO inhibitors as systemic
      immunomodulators to be combined with other immune modulators, vaccines, and
      chemotherapy are ongoing.

PMID- 20693849
TI  - Adoptive therapy using antigen-specific T-cell clones.
AB  - T-cell therapy involves the ex vivo isolation and expansion of antigen-specific T
      cells for adoptive transfer. The use of T-cell clones represents one embodiment
      of this approach and provides a uniform population of effector cells, so that
      parameters contributing to an effective response can be rigorously evaluated. T
      cells of defined specificity, phenotype, and function are isolated and expanded;
      when infused into patients, these intrinsic factors can be considered in light of
      extrinsic factors such as the type of conditioning regimen, cytokine support, and
      immunomodulatory reagents. In this chapter, 2 topics related to the use of
      antigen-specific T-cell clones are discussed: first, advances enabling the
      isolation and expansion of antigen-specific T-cell clones for human trials of
      adoptive therapy, and second, a contextual framework of advantages and
      limitations in which the use of adoptively transferred T-cell clones can be
      judiciously applied as a means to dissect the requirements for effective therapy.

PMID- 20693848
TI  - Interface of signal transduction inhibition and immunotherapy in melanoma.
AB  - Food and Drug Administration-approved treatment for metastatic melanoma,
      including interferon alpha and interleukin-2, offer a modest benefit.
      Immunotherapy, although has not enjoyed high overall response rates, is capable
      of providing durable responses in a subset of patients. In recent years, new
      molecular-targeted therapies have become available and offer promise of clinical
      benefit, although low durability of response. It is not yet clear how best to
      integrate these 2 novel modalities that target the immune response to melanoma
      (immune therapy) or that target molecular signaling pathways in the melanoma
      cells (targeted therapy). Many signal transduction pathways are important in both
      tumor cell and T-cell proliferation and survival, which generate risk in
      combining targeted therapy and immunotherapy. This review focuses on the role of
      targeted therapy and immunotherapy in melanoma, and discusses how to combine the
      2 modalities rationally for increased duration and response.

PMID- 20693850
TI  - Artificial antigen-presenting cells for use in adoptive immunotherapy.
AB  - The observation that T cells can recognize and specifically eliminate cancer
      cells has spurred interest in the development of efficient methods to generate
      large numbers of T cells with specificity for tumor antigens that can be
      harnessed for use in cancer therapy. Recent studies have demonstrated that during
      encounter with tumor antigen, the signals delivered to T cells by professional
      antigen-presenting cells can affect T-cell programming and their subsequent
      therapeutic efficacy. This has stimulated efforts to develop artificial antigen
      presenting cells that allow optimal control over the signals provided to T cells.
      In this review, we will discuss the advantages and disadvantages of cellular and
      acellular artificial antigen-presenting cell systems and their use in T-cell
      adoptive immunotherapy for cancer.

PMID- 20693852
TI  - Novel gamma-chain cytokines as candidate immune modulators in immune therapies
      for cancer.
AB  - Cytokines that signal through the common-gamma chain are potent growth factors
      for T cells and natural killer cells. Interleukin (IL)-2, the gammac prototype,
      can mediate antitumor effects as a single agent or in the context of
      multimodality regimens but is limited by side effects and a propensity for
      expansion of regulatory T cells. IL-7, IL-15, and IL-21 each possess properties
      that can be exploited in the context of immunotherapy for cancer. Each has been
      demonstrated to mediate potent vaccine adjuvant effects in tumor models, and each
      can enhance the effectiveness of adoptive immunotherapies. Although the overlap
      among the agents is significant, IL-7 is uniquely immunorestorative and
      preferentially augments reactivity of naive populations, IL-15 potently augments
      reactivity of CD8 memory cells and natural killer cells, and IL-21 preferentially
      expands the inflammatory Th17 subset and may limit terminal differentiation of
      effector CD8 cells. Clinical trials of IL-7 and IL-21 have already been completed
      and, so far, demonstrate safety and biologic activity of these agents. Clinical
      trials of IL-15 are expected soon. Ultimately, these agents are expected to be
      most effective in the context of multimodal immunotherapy regimens, and careful
      clinical trial design will be needed to efficiently identify the proper doses,
      regimens, and settings in which to exploit their biologic properties for
      therapeutic gain.

PMID- 20693853
TI  - Gene signature in melanoma associated with clinical activity: a potential clue to
      unlock cancer immunotherapy.
AB  - Immunotherapeutic approaches for melanoma and other cancers can impart profound
      clinical benefit but only for a subset of patients. Interpatient heterogeneity
      could, in principle, be due to somatic differences in the tumor between
      individuals or alternatively be accounted for distinct germline polymorphisms in
      immunoregulatory genes of the host. Analysis of these possibilities has been
      initiated by investigating gene expression profiling of the tumor
      microenvironment in the context of clinical trials of cancer vaccines. Distinct
      gene expression profiles have been identified on pretreatment biopsies that are
      associated with a positive or negative clinical outcome. These observations
      suggest that such profiling might be useful as a predictive biomarker for
      clinical benefit from vaccines and other immunotherapy approaches, and analysis
      of specific gene products has begun to suggest new therapeutic interventions to
      overcome mechanisms of tumor resistance.

PMID- 20693851
TI  - Toll-like receptor agonists: are they good adjuvants?
AB  - Therapeutic immunization leading to cancer regression remains a significant
      challenge. Successful immunization requires activation of adaptive immunity,
      including tumor specific CD4 T cells and CD8 T cells. Generally, the activation
      of T cells is compromised in patients with cancer because of immune suppression,
      loss of tumor antigen expression, and dysfunction of antigen-presenting cells.
      Antigen-presenting cells such as dendritic cells (DCs) are key for the induction
      of adaptive antitumor immune responses. Recently, attention has focused on novel
      adjuvants that enhance dendritic cell function and their ability to prime T
      cells. Agonists that target toll-like receptors are being used clinically either
      alone or in combination with tumor antigens and showing initial success both in
      terms of enhancing immune responses and eliciting antitumor activity. This review
      summarizes the application of these adjuvants to treat cancer and the potential
      for boosting responses in vivo.

PMID- 20693854
TI  - Reversal of intractable hypoxemia with exogenous surfactant (calfactant)
      facilitating complete neurological recovery in a pediatric drowning victim.
AB  - OBJECTIVE: To report the successful reversal of intractable hypoxemia after
      exogenous surfactant (calfactant) administration, facilitating neurological
      recovery in a toddler cold-water drowning victim with significant circulatory
      arrest time. METHODS: Case report and review of literature. RESULTS: A 2(1/2)
      year-old girl cold-water drowning victim with severe, intractable hypoxemia after
      submersion time of approximately 15 minutes and arrest time of approximately 45
      minutes was given 80 mL/m of calfactant endotracheally with reversal of her
      hypoxemia and eventual neurologically intact survival. CONCLUSIONS: Surfactant
      replacement with calfactant is a rational, useful, and potentially lifesaving
      treatment for acute hypoxemic respiratory failure due to drowning.

PMID- 20693855
TI  - Toddler with seizures due to ingesting camphor at an Indian celebration.
AB  - We report a 3-year-old girl who presented to the emergency department with
      seizures. Earlier in the evening, the patient was with her parents at an Indian
      celebration where she vomited once and then became hyperactive. Fifteen minutes
      later, she became unresponsive and had an episode characterized by eye blinking,
      teeth grinding, and posturing that lasted 2 to 3 minutes. To our knowledge, this
      is the first report of seizure after ingestion of ceremonial camphor tablets at
      an Indian ceremony. Given the inadequate packaging and use of many grams of
      camphor at these ceremonies, the pediatric population specifically is at risk for
      camphor toxicity from this source. Health care professionals should be aware of
      this unique and culturally specific source of potential camphor toxicity.

PMID- 20693856
TI  - Recurrent coagulopathy and thrombocytopenia in children treated with crotalidae
      polyvalent immune fab: a case series.
AB  - OBJECTIVES: Recurrent signs and symptoms after initial treatment and control of
      coagulopathy and thrombocytopenia after American pit viper (crotaline)
      envenomations have been previously described in patients treated with Crotalidae
      polyvalent immune Fab antivenom (FabAV). The significance and necessity of
      treatment of these recurrent abnormalities are uncertain. Our goal was to further
      characterize recurrent coagulopathy or thrombocytopenia in pediatric patients.
      METHODS: All cases presenting to our Toxicology Consult Service, which covers 6
      hospitals in a metropolitan area, from May 2007 to April 2008 with recurrent
      coagulopathy after initial control with FabAV were included and retrospectively
      reviewed. RESULTS: Four cases of pediatric patients are presented who presented
      with recurrent coagulopathy and/or thrombocytopenia after initial control with
      FabAV. The patients were all treated with delayed administration of FabAV with
      variable results. Blood products administered without concurrent FabAV were of
      limited use. The laboratory abnormalities took up to 18 days to resolve in one
      case. One patient developed hemodynamically significant spontaneous bleeding.
      CONCLUSIONS: The cases presented here suggest administration of FabAV may correct
      delayed coagulopathy associated with crotaline envenomations. The first 3 cases
      illustrate that in the face of severe derangements in laboratory values, most
      envenomated patients treated with FabAV do not develop significant bleeding.
      These cases may respond to additional antivenom alone. However, case 4
      illustrates that hemodynamically significant spontaneous bleeding can occur.
      Until more data are available, readministration of FabAV is a reasonable first
      line therapy for delayed coagulopathy associated with crotaline envenomations.

PMID- 20693857
TI  - Henoch-schonlein purpura complicated by reversible posterior leukoencephalopathy
      syndrome.
AB  - We report a 7-year-old girl with Henoch-Schonlein purpura who developed
      hypertensive encephalopathy. She showed a sudden onset of neurological symptoms,
      including hypertension, convulsions, disturbance of consciousness, and cortical
      blindness. Reversible posterior leukoencephalopathy syndrome was diagnosed from
      the findings on magnetic resonance imaging. Reports of this syndrome in patients
      with Henoch-Schonlein purpura are very rare. However, if symptoms suggest central
      nervous system involvement, neuroimaging should be done for rapid diagnosis, and
      immediate treatment should be provided to avoid sequelae.

PMID- 20693858
TI  - Point-of-care sonographic detection of intestinal ascaris lumbricoides in the
      pediatric emergency department.
AB  - Point-of-care ultrasound use is rapidly growing in acute-care settings such as
      pediatric emergency departments, and new applications are continually being
      explored. This is especially true in the developing world where the World Health
      Organization estimates that 75% of people have no access to any imaging or
      availability of more costly imaging technology may be limited (Essential Health
      Technologies Strategy 2004-2007). We report a case of intestinal roundworm
      infection in a 3-year-old boy and describe the ultrasound findings of Ascaris
      lumbricoides.

PMID- 20693859
TI  - Spontaneous pneumomediastinum: a report of 2 cases.
AB  - We report 2 cases of spontaneous pneumomediastinum (SPM) with clinical
      presentations similar to pericarditis, including positional chest pain,
      tachycardia, a precordial rub, and electrocardiographic changes. Chest
      radiography is the most commonly used imaging modality for diagnosis, but the
      findings may be subtle. In select patients, a more extensive diagnostic approach
      is warranted. Spontaneous pneumomediastinum is self-limiting, and the risk of
      recurrence is negligible. These cases serve to illustrate the need to include
      spontaneous pneumomediastinum in the differential diagnosis of pericarditis.

PMID- 20693860
TI  - Acute pancreatitis due to rotavirus gastroenteritis in a child.
AB  - OBJECTIVES: Serum amylase can be elevated in various pathological conditions, but
      its primary application is as a biochemical test for the diagnosis of acute
      pancreatitis. Acute gastroenteritis has not been widely recognized as a cause for
      hyperamylasemia and pancreatitis. METHODS: We describe a case of acute
      pancreatitis after rotavirus gastroenteritis occurring in a previously healthy
      child. RESULTS: Rotavirus infection was demonstrated by detection of virus
      particles in stool culture and pancreatitis by raised serum amylase and lipase
      levels. No abnormalities were noticed during clinical follow-up. CONCLUSIONS:
      Further investigation to understand the role of rotavirus as a cause of
      pancreatitis in children may be helpful.

PMID- 20693861
TI  - An update on the epidemiology of pediatric fractures.
AB  - Despite public health measures to prevent childhood injuries, the incidence of
      pediatric fractures is increasing. This fracture incidence is dependent on many
      demographic factors, the various contributors to bone health, and an individual's
      risk-taking behavior. Although traditional play activities continue to be the
      prevalent causes for fractures, there is an evolving array of new sport and
      recreation activities that carry significant fracture risk. The following review
      article outlines the developing epidemiology of pediatric fractures by analyzing
      some of the individual risk factors that influence fracture incidence as well as
      the variety of activities that are associated with these fractures.

PMID- 20693863
TI  - Pediatric emergency medicine: legal briefs.

PMID- 20693864
TI  - Clinical impression: intussusception: an abdominal ultrasound is obtained:
      surprise.

PMID- 20693865
TI  - ECGs in the ED.

PMID- 20693866
TI  - Coping strategies influence caregiver outcomes among Asian family caregivers of
      persons with dementia in Singapore.
AB  - This cross-sectional study used the stress and coping paradigm to examine the
      factors associated with negative and positive adjustment outcomes among Asian
      family caregivers of persons with dementia (PWD) in Singapore. One hundred seven
      family caregivers completed measures assessing patient illness characteristics,
      general coping styles of caregivers, specific dementia management strategies,
      religion and spirituality, and caregiver adjustment outcomes of burden and gain.
      Multiple regressions revealed that behavioral problems in the PWD, dementia
      severity, and the use of behavioral disengagement and criticism as coping
      strategies were significant predictors of burden accounting for 48% of the
      explained variance [F(4,99)=23.12, P<0.001]. The only significant predictor of
      gain was the use of encouragement as a specific dementia management strategy,
      explaining 18% of variance [F(3,102)=7.39, P<0.001]. Religion and spirituality
      predicted gain indirectly through the use of encouragement. Coping strategies had
      an independent effect on caregiver outcomes above and beyond PWD illness
      characteristics and caregiver characteristics. Hence, caregiver interventions
      should target coping strategies to improve outcomes of caregiving for dementia.
      Findings also support the need to examine religion and spirituality in future
      studies of caregiver adjustment outcomes and to explore the factors not measured
      in this study that might explain gain.

PMID- 20693867
TI  - Treatment of a patient with dementia and inappropriate sexual behaviors with
      citalopram.
AB  - Inappropriate sexual behaviors (ISBs) associated with dementias and their
      treatment have not been commonly reported in the medical literature. This report
      presents an elderly male patient with moderately severe dementia and incident
      onset of ISBs who was treated with citalopram (20-mg daily) and subsequently
      displayed a reduction in ISBs. A review of the literature suggests that ISBs may
      be underrecognized and undertreated, and therefore should be actively monitored
      and treated. 

PMID- 20693868
TI  - Combined clinical and cognitive criteria to identify mild cognitive impairment in
      a southern Chinese community.
AB  - Mild Cognitive Impairment (MCI) is a recognized risk condition for clinical
      dementia. This paper attempted to explore the applicability of a combined
      cognitive and clinical approach to identify older Chinese adults at-risk of
      cognitive decline. Seven hundred forty randomly recruited community dwelling
      participants (aged 60 or over) were assessed at baseline and 2 years with
      Clinical Dementia Rating (CDR) and a cognitive battery. Baseline MCI groups were
      categorized by CDR-MCI, cognitive function (Cog-MCI), and a combined CDR-Cog
      approach. The cognitive approach adopted the Mayo clinic criteria. For the
      combined approach, nonamnestic MCI combined CDR 0.5 plus nonmemory cognitive
      deficits. The overall concordance between CDR and Cognitive test ratings were
      65.3% (chi2 = 256.4, P<0.001, kappa=0.44). With a combined approach, 424 (57%)
      participants were classified as normal. CDR-MCI group had higher cognitive scores
      compared with MCI groups by other criteria (1 way analysis of variance or ANOVA).
      At 2 years, the combined CDR-Cog MCI group identified all dementia (N=24)
      converters although group differences were not significant. Cognitive function
      and CDR identified participants potentially at-risk for furthermore decline, but
      exhibited some differences in detection profiles. A combined approach may be more
      practical in screening for MCI participants with diverse educational and cultural
      background.

PMID- 20693869
TI  - Preserving patients' health during WWII. Commentary.

PMID- 20693870
TI  - Taming the ketamine tiger. 1965.
AB  - Pharmacologic actions of CI-581, a chemical derivative of phencyclidine, were
      determined in 20 volunteers from a prison population. The results indicate that
      this drug is an effective analgesic and anesthetic agent in doses of 1.0 to 2.0
      mg per kilogram. With intravenous administration the onset of action is within 1
      min and the effects last for about 5 to 10 min, depending on dosage level and
      individual variation. No tachyphylaxis was evident on repeat doses. Respiratory
      depression was slight and transient. Hypertension, tachycardia, and psychic
      changes are undesirable characteristics of the drug. Whether these can be
      modified by preanesthetic medication was not determined in this study. Recovery
      from analgesia and coma usually took place within 10 min, although from
      electroencephalographic evidence it may be assumed that subjects were not
      completely normal until after 1 to 2 h. No evidence of liver or kidney toxicity
      was obtained. CI-581 produces pharmacologic effects similar to those reported for
      phencyclidine, but of shorter duration. The drug deserves further pharmacologic
      and clinical trials. It is proposed that the words "dissociative anesthetic" be
      used to describe the mental state produced by this drug.

PMID- 20693871
TI  - Inhibitors of angiogenesis: new hopes for oncologists, new challenges for
      anesthesiologists.

PMID- 20693873
TI  - Clinical teaching improves with resident evaluation and feedback.
AB  - BACKGROUND: The literature is mixed on whether evaluation and feedback to
      clinical teachers improves clinical teaching. This study sought to determine
      whether resident-provided numerical evaluation and written feedback to clinical
      teachers improved clinical teaching scores. METHODS: Anesthesia residents
      anonymously provided numerical scores and narrative comments to faculty members
      who provided clinical teaching. Residents returned 19,306 evaluations between
      December 2000 and May 2006. Faculty members received a quantitative summary
      report and all narrative comments every 6 months. Residents also filled out
      annual residency program evaluations in which they listed the best and worst
      teachers in the department. RESULTS: The average teaching score for the entire
      faculty rose over time and reached a plateau with a time constant of
      approximately 1 yr. At first, individual faculty members had average teaching
      scores that were numerically diverse. Over time, the average scores became more
      homogeneous. Faculty members ranked highest by teaching scores were also most
      frequently named as the best teachers. Faculty members ranked lowest by teaching
      scores were most frequently named as the worst teachers. Analysis of ranks,
      differential improvement in scores, and a decrease in score diversity effectively
      ruled out simple score inflation as the cause for increased scores. An increase
      in teaching scores was most likely due to improved teaching. CONCLUSIONS: A
      combination of evaluation and feedback, including comments on areas for
      improvement, was related to a substantial improvement in teaching scores.
      Clinical teachers are able to improve by using feedback from residents.

PMID- 20693874
TI  - A role for acid-sensing ion channel 3, but not acid-sensing ion channel 2, in
      sensing dynamic mechanical stimuli.
AB  - BACKGROUND: Acid-sensing ion channels 2 and 3 (ASIC2 and ASIC3, respectively)
      have been implicated as putative mechanotransducers. Because mechanical
      hyperalgesia is a prominent consequence of nerve injury, we tested whether male
      and female ASIC2 or ASIC3 knockout mice have altered responses to mechanical and
      heat stimuli at baseline and during the 5 weeks after spinal nerve ligation.
      METHODS: Age-matched, adult male and female ASIC2 knockout (n=21) and wild-type
      (WT; n=24) mice or ASIC3 knockout (n=20) and WT (n=19) mice were tested for
      sensitivity to natural stimuli before and after spinal nerve ligation surgery.
      All animals were first tested for baseline sensitivity to mechanical and heat
      stimuli and in a novel dynamic mechanical stimulation test. The same testing
      procedures were then repeated weekly after spinal nerve injury. RESULTS: Compared
      with their respective WT counterparts, ASIC2 and ASIC3 knockout mice had normal
      baseline sensitivity to standard mechanical and heat stimuli. However, when
      exposed to a novel stroking stimulus to test sensitivity to dynamic mechanical
      stimulation, ASIC3 knockout mice were significantly more sensitive than were WT
      mice. After spinal nerve ligation, ASIC2 and ASIC3 knockout mice developed
      mechanical and heat hyperalgesia comparable with that of their respective WT
      controls. In addition, in both experiments, female mice were more sensitive than
      male mice to heat at baseline and after the nerve injury. CONCLUSIONS: We
      conclude that ASIC2 and ASIC3 channels are not directly involved in the
      development or maintenance of neuropathic pain after spinal nerve ligation.
      However, the ASIC3 channel significantly modulates the sensing of dynamic
      mechanical stimuli in physiologic condition.

PMID- 20693875
TI  - In vivo fluorescence-mediated tomography for quantification of urokinase receptor
      dependent leukocyte trafficking in inflammation.
AB  - BACKGROUND: Inflammation is characterized by leukocyte recruitment. Macrophages
      and neutrophils contribute to tissue damage and organ dysfunction. Modulating
      leukocyte invasion can protect from these adverse effects. Leukocyte recruitment
      critically depends on the urokinase-type plasminogen activator receptor (u-PAR).
      We here use a novel technique to longitudinally quantify cell trafficking in
      inflammatory models in live animals. METHODS: Near-infrared fluorophore-labeled
      leukocytes were adoptively transferred to mice with thioglycollate peritonitis to
      study leukocyte trafficking to sites of inflammation. Macrophage and neutrophil
      trafficking was followed with three-dimensional fluorescence-mediated-tomography.
      u-PAR-/- and wild-type macrophage recruitment was studied by cross-over adoptive
      cell transfer to elucidate the role of leukocytic versus u-PAR expressed on other
      cells. Endotoxic shock-induced pulmonary inflammation was used to study u-PARs
      role for pulmonary neutrophil recruitment. RESULTS: Mice experiencing peritonitis
      showed a significant increase in mean fluorescence intensity because of enhanced
      macrophage (315%, n=9-10), P<0.05) or neutrophil (194%, n=6, P<0.02) recruitment.
      Fluorescence-mediated-tomography uncovered a macrophage recruitment defect in the
      peritonitis model for u-PAR-/- mice (147% of baseline) compared with control mice
      (335% of baseline, n=8-9, P<0.05). When u-PAR-/--macrophages were transferred to
      wild-type mice fluorescence intensity increased to 145% while wild-type
      macrophage transfer into u-PAR-/- resulted in 192% increase compared with
      baseline (n=6, P<0.05). Reduced neutrophil recruitment in pulmonary inflammation
      in u-PAR-/- mice was accompanied by improved pulmonary gas exchange. CONCLUSION:
      Using noninvasive in vivo fluorescence-mediated tomography to image leukocyte
      recruitment in inflammatory mouse models, we describe a novel macrophage
      recruitment defect in u-PAR-/- mice. Targeting u-PAR for modulation of leukocyte
      recruitment is a promising therapeutic strategy to ameliorate leukocyte induced
      tissue damage.

PMID- 20693876
TI  - Intraoperative ketamine reduces perioperative opiate consumption in opiate
      dependent patients with chronic back pain undergoing back surgery.
AB  - BACKGROUND: Ketamine is an N-methyl-d-aspartate receptor antagonist that has been
      shown to be useful in the reduction of acute postoperative pain and analgesic
      consumption in a variety of surgical interventions with variable routes of
      administration. Little is known regarding its efficacy in opiate-dependent
      patients with a history of chronic pain. We hypothesized that ketamine would
      reduce postoperative opiate consumption in this patient population. METHODS: This
      was a randomized, prospective, double-blinded, and placebo-controlled trial
      involving opiate-dependent patients undergoing major lumbar spine surgery. Fifty
      two patients in the treatment group were administered 0.5 mg/kg intravenous
      ketamine on induction of anesthesia, and a continuous infusion at 10 microg kg(
      1) min(-1) was begun on induction and terminated at wound closure. Fifty patients
      in the placebo group received saline of equivalent volume. Patients were observed
      for 48 h postoperatively and followed up at 6 weeks. The primary outcome was 48-h
      morphine consumption. RESULTS: Total morphine consumption (morphine equivalents)
      was significantly reduced in the treatment group 48 h after the procedure. It was
      also reduced at 24 h and at 6 weeks. The average reported pain intensity was
      significantly reduced in the postanesthesia care unit and at 6 weeks. The groups
      had no differences in known ketamine- or opiate-related side effects.
      CONCLUSIONS: Intraoperative ketamine reduces opiate consumption in the 48-h
      postoperative period in opiate-dependent patients with chronic pain. Ketamine may
      also reduce opioid consumption and pain intensity throughout the postoperative
      period in this patient population. This benefit is without an increase in side
      effects.

PMID- 20693877
TI  - Influence of tidal volume on pulse pressure variations in hypovolemic ventilated
      pigs with acute respiratory distress-like syndrome.
AB  - BACKGROUND: Sensitivity and specificity of respiratory change in pulse pressure
      (DeltaPP) to predict preload dependency has been questioned at small tidal
      volumes (VT) in critically ill patients suffering from acute respiratory distress
      syndrome (ARDS). We studied DeltaPP in pigs with ARDS-like syndrome during
      reversible hemorrhagic shock. METHODS: Prospective, observational animal study in
      a Laboratory Investigation Unit. Sixteen deeply sedated mechanically ventilated
      pigs were successively ventilated with VT of 10 ml/kg at a respiratory rate of 15
      breaths/min (RR15) and VT of 6 ml/kg at RR15 and RR25. ARDS-like syndrome was
      produced by lung lavage in eight pigs (ARDS group). Severe hemorrhagic shock was
      induced by removal of 40% of total blood volume followed by restoration. RESULTS:
      After bleeding, in the control group ventilated with a VT of 10 ml/kg, DeltaPP
      increased from 8.5 (95% confidence interval [CI], 7.1 to 9.9%) to 18.5% (CI, 15.3
      to 21.7%; P<0.05). In the ARDS group, this index increased similarly, from 7.1%
      (95% CI, 5.3 to 9.0%) to 20.1% (CI, 15.3 to 24.9%; P<0.05). In control lungs,
      reduction in VT from 10 to 6 ml/kg reduced the DeltaPP reaction by 40%, although
      it remained a statistically valid indicator of hypovolemia regardless of the RR
      value. In contrast, in the ARDS group, DeltaPP was an unreliable hypovolemia
      marker at low VT ventilation, regardless of the RR value (p=not statistically
      significant). CONCLUSIONS: The present study suggests that DeltaPP is a reliable
      indicator of severe hypovolemia in pigs with healthy lungs regardless of VT or
      RR. In contrast, in pigs with ARDS-like syndrome ventilated with small VT,
      DeltaPP is not a good indicator of severe hemorrhage. However, in this setting,
      indexing DeltaPP to respiratory changes in transpulmonary pressure allows this
      marker to significantly indicate the occurrence of hypovolemia.

PMID- 20693878
TI  - Block of neuronal Na+ channels by antidepressant duloxetine in a state-dependent
      manner.
AB  - BACKGROUND: Duloxetine is a mixed serotonin-norepinephrine reuptake inhibitor
      used for major depressive disorder. Duloxetine is also beneficial for patients
      with diabetic peripheral neuropathy and with fibromyalgia, but how it works
      remains unclear. METHODS: We used the whole cell, patch clamp technique to test
      whether duloxetine interacts with the neuronal Nav1.7 Na+ channel as a potential
      target. Resting and inactivated Nav1.7 Na+ channel block by duloxetine were
      measured by conventional pulse protocols in transfected human embryonic kidney
      cells. The open-channel block was determined directly using inactivation
      deficient mutant Nav1.7 Na+ channels. RESULTS: The 50% inhibitory concentration
      (IC50) of duloxetine for the resting and inactivated wild-type hNav1.7 Na+
      channel were 22.1+/-0.4 and 1.79+/-0.10 microM, respectively (mean+/-SE, n=5).
      The IC50 for the open Na+ channel was 0.25+/-0.02 microM (n=5), as determined by
      the block of persistent late Nav1.7 Na+ currents. Similar open-channel block by
      duloxetine was found in the muscle Nav1.4 isoform (IC50=0.51+/-0.05 microM; n=5).
      Block by duloxetine appeared via the conserved local anesthetic receptor as
      determined by site-directed mutagenesis. Finally, duloxetine elicited strong use
      dependent block of neuronal transient Nav1.7 Na+ currents during repetitive
      stimulations. CONCLUSIONS: Duloxetine blocks persistent late Nav1.7 Na+ currents
      preferentially, which may in part account for its analgesic action.

PMID- 20693880
TI  - Cervical epidural pressure measurement: comparison in the prone and sitting
      positions.
AB  - BACKGROUND: The hanging drop technique is used for identifying the cervical
      epidural space, using its negative pressure. However, it is doubtful whether the
      epidural space intrinsically exhibits a negative pressure. We designed this study
      to test the hypothesis that the cervical epidural pressure (CEP) is significantly
      higher in the prone position than in the sitting position. To evaluate this
      hypothesis, we measured and compared 30 CEP values in the prone and sitting
      positions. METHODS: We measured and compared 15 CEPs in the prone group and 15 in
      the sitting group using a closed pressure measurement system under fluoroscopic
      guidance. RESULTS: All CEPs in the prone group were consistently positive
      (median, 10 mmHg; range, 4.8-18.7; mean+/-SD, 10.5+/-4.4) in contrast to the
      sitting group (median, -0.3 mmHg; range, -2.4-7.9; mean+/-SD, 0.5+/-2.8). CEPs in
      the prone group were significantly higher than in the sitting group (P<0.001).
      CONCLUSION: CEP was found to be significantly higher in the prone position than
      in the sitting position. Furthermore, CEPs were not consistently negative even in
      the sitting position. These results suggest that the hanging drop technique is
      inappropriate for identifying the cervical epidural space in either the prone or
      sitting positions. Clinical Trials Ref: NCT01009385.

PMID- 20693879
TI  - Sevoflurane binds and allosterically blocks integrin lymphocyte function
      associated antigen-1.
AB  - BACKGROUND: Volatile anesthetics have been shown to modify immune cell functions
      via several mechanisms, some of which have been only partially elucidated. We
      demonstrated that isoflurane inhibits primary leukocyte integrin lymphocyte
      function-associated antigen-1 (LFA-1) by binding to the allosteric cavity
      critical for conformational activation to its high-affinity form. It remains to
      be determined whether the allosteric inhibition of LFA-1 by isoflurane can be
      generalized to other anesthetics such as sevoflurane. METHODS: The effects of
      sevoflurane on the ability of LFA-1 to bind to its counter-ligand, intercellular
      adhesion molecule-1, was studied in leukocytes by flow cytometry. To examine
      whether sevoflurane acts directly on LFA-1, we measured ligand-binding using
      beads coated with purified LFA-1 protein. To distinguish between competitive
      versus allosteric inhibition, we analyzed the effects of sevoflurane on both wild
      type and mutant-locked high-affinity LFA-1. One-way analysis of variance was
      employed for statistical analysis of the data. Nuclear magnetic resonance
      spectroscopy was used to identify sevoflurane binding site(s). RESULTS:
      Sevoflurane at clinically relevant concentrations inhibited the ligand-binding
      function of LFA-1 in leukocytes as well as in cell-free assays (P<0.05).
      Sevoflurane blocked wild-type but not locked high-affinity LFA-1, thereby
      demonstrating an allosteric mode of inhibition. Nuclear magnetic resonance
      spectroscopy revealed that sevoflurane bound to the allosteric cavity, to which
      LFA-1 allosteric antagonists and isoflurane also bind. CONCLUSIONS: This study
      suggests that sevoflurane also blocks the activation-dependent conformational
      changes of LFA-1 to the high-affinity form. The allosteric mode of action
      exemplified by sevoflurane and isoflurane via LFA-1 might represent one of the
      underlying mechanisms of anesthetic-mediated immunomodulation.

PMID- 20693881
TI  - Variations in pharmacology of beta-blockers may contribute to heterogeneous
      results in trials of perioperative beta-blockade.
AB  - BACKGROUND: Randomized controlled trials and meta-analyses provide conflicting
      guidance on the role of beta-adrenergic receptor blockers (beta-blockers) in
      reducing perioperative complications. We hypothesize that variability in trial
      results may be due in part to heterogeneous properties of beta-blockers. First,
      we propose that the extent of beta-blocker metabolism by cytochrome P-450 and the
      time available to titrate the dosage before surgery (titration time) may
      interact; dependence on P-450 may be most harmful when titration time is short.
      Second, beta-blockers vary in their selectivity for the beta-1 receptor and
      reduced selectivity may contribute to cerebral ischemia. METHODS: We used meta
      analysis and meta-regression of existing trials to explore the role of these
      pharmacological properties. RESULTS: We found that both of these pharmacological
      factors are significantly associated with reduced efficacy of beta-blockers.
      CONCLUSIONS: Pharmacological properties of beta-blockers may contribute to
      heterogeneous trial results. Many trials have used metoprolol, which is
      extensively metabolized by cytochrome P450 and is less selective for the beta-1
      receptor. For these two reasons, the efficacy of metoprolol to prevent
      perioperative cardiac complications should be compared with the efficacy of other
      beta-blockers.

PMID- 20693882
TI  - Pregnancy does not enhance volatile anesthetic sensitivity on the brain: an
      electroencephalographic analysis study.
AB  - BACKGROUNDS: Parturients are thought to be more sensitive to inhalational
      anesthetics because their minimum alveolar concentration is decreased. However,
      this conventional theory may be wrong, because, according to recent animal
      studies, minimum alveolar concentration indicates anesthetic effect on the spinal
      cord but not on the brain. The aim of this electroencephalographic study was to
      investigate the differences in the hypnotic effect of sevoflurane on parturients
      and nonpregnant patients. METHODS: Fifteen parturients undergoing cesarean
      section and 15 patients undergoing elective gynecologic surgery were enrolled.
      Anesthesia was induced with 4 mg/kg thiopental, 2 microg/kg fentanyl, and 2 mg/kg
      suxamethonium or 0.15 mg/kg vecuronium. Anesthesia was maintained with
      sevoflurane and fentanyl. The electroencephalographic signals, obtained from the
      bispectral index monitor, were recorded on a computer. We calculated 95% spectral
      edge frequency, amplitude, and bicoherence using custom software (Bispectrum
      Analyzer for bispectral index). After confirming that end-tidal sevoflurane had
      reached equilibrium, we measured electroencephalographic parameters of
      sevoflurane at 2.0 and 1.5% during surgery and at 1.0 and 0.5% after surgery.
      RESULTS: With the decrease of end-tidal sevoflurane concentration from 2.0 to
      0.5%, 95% spectral edge frequency, amplitude, bispectral index, and bicoherence
      values changed dose-dependently in pregnant and nonpregnant women (P<0.0001).
      However, there were no significant differences in those electroencephalographic
      parameters in pregnant and nonpregnant women. CONCLUSIONS: This
      electroencephalographic study has shown that pregnancy does not enhance hypnotic
      effect of sevoflurane. These results suggested that the decrease in minimum
      alveolar concentration during pregnancy does not mean an enhanced volatile
      anesthetic effect on the brain.

PMID- 20693883
TI  - An update on the pathophysiology of complex regional pain syndrome.
AB  - Complex regional pain syndrome (CRPS) is a neuropathic pain disorder with
      significant autonomic features. Few treatments have proven effective, in part,
      because of a historically poor understanding of the mechanisms underlying the
      disorder. CRPS research largely conducted during the past decade has
      substantially increased knowledge regarding its pathophysiologic mechanisms,
      indicating that they are multifactorial. Both peripheral and central nervous
      system mechanisms are involved. These include peripheral and central
      sensitization, inflammation, altered sympathetic and catecholaminergic function,
      altered somatosensory representation in the brain, genetic factors, and
      psychophysiologic interactions. Relative contributions of the mechanisms
      underlying CRPS may differ across patients and even within a patient over time,
      particularly in the transition from "warm CRPS" (acute) to "cold CRPS" (chronic).
      Enhanced knowledge regarding the pathophysiology of CRPS increases the
      possibility of eventually achieving the goal of mechanism-based CRPS diagnosis
      and treatment.

PMID- 20693884
TI  - Fentanyl-sparing effect of acetaminophen as a mixture of fentanyl in intravenous
      parent-/nurse-controlled analgesia after pediatric ureteroneocystostomy.
AB  - BACKGROUND: Although acetaminophen has been used widely and is well tolerated in
      children, its efficacy and safety have not been clarified when combined with an
      opioid in intravenous parent-/nurse-controlled postoperative analgesia. METHODS:
      Sixty-three children (aged 6-24 months) who had undergone elective
      ureteroneocystostomies were enrolled in this prospective, randomized, double
      blinded study. After the surgery, an analgesic pump was programmed to deliver
      fentanyl at a basal infusion rate of 0.25 microg.kg(-1).h(-1) and 0.25 microg/kg
      bolus after a loading dose of 0.5 microg/kg(-1). In the fentanyl-acetaminophen
      group, acetaminophen was coadministered as a solution mixture at a basal infusion
      rate of 1.5 mg.kg(-1).h(-1) and 1.5 mg/kg bolus after a loading dose of 15 mg/kg,
      whereas saline was administered to the fentanyl group. RESULTS: Postoperative
      pain scores were similar between the two groups. The total dose (micrograms per
      kilogram per day, mean+/-SD) of fentanyl at postoperative days 1 (8.3+/-3.7 vs.
      18.1+/-4.6, P=0.021) and 2 (7.0+/-2.4 vs. 16.6, P=0.042) was significantly less
      in the fentanyl-acetaminophen group compared with that in the fentanyl group. The
      incidences of vomiting (16.1 vs. 56.3%, P=0.011) and sedation (9.7 vs. 46.9%,
      P=0.019) were significantly lower in the fentanyl-acetaminophen group than those
      in the fentanyl group. CONCLUSIONS: Acetaminophen has significant fentanyl
      sparing effects and reduces side effects when combined with fentanyl in
      intravenous parent-/nurse-controlled analgesia for postoperative pediatric pain
      management.

PMID- 20693885
TI  - Trachea rupture in tenascin-X-deficient type Ehlers-Danlos syndrome.

PMID- 20693886
TI  - C1-esterase inhibitor attenuates the inflammatory response during human
      endotoxemia.
AB  - OBJECTIVE: Besides its role in regulation of the complement and contact system,
      C1-esterase inhibitor has other immunomodulating effects that could prove
      beneficial in patients with acute inflammation such as during sepsis or after
      trauma. We examined the immunomodulating properties of C1-esterase inhibitor
      during human experimental endotoxemia, in which the innate immune system is
      activated in the absence of activation of the classic complement pathway. DESIGN:
      Double-blind placebo-controlled study. SETTING: Research intensive care unit of
      the Radboud University Nijmegen Medical Centre. SUBJECTS: Twenty healthy
      volunteers. INTERVENTIONS: Intravenous injection of 2 ng/kg Escherichia coli
      lipopolysaccharide. Thirty minutes thereafter (to prevent binding of
      lipopolysaccharide), C1-esterase inhibitor concentrate (100 U/kg, n = 10) or
      placebo (n = 10) was infused. MEASUREMENTS AND MAIN RESULTS: Pro- and anti
      inflammatory mediators, markers of endothelial and complement activation,
      hemodynamics, body temperature, and symptoms were measured. C1-esterase inhibitor
      reduced the release of proinflammatory cytokines as well as C-reactive protein
      (peak levels of: interleukin-6 1521 +/- 209 vs. 932 +/- 174 pg/mL [p = .04],
      tumor necrosis factor-alpha 1213 +/- 187 vs. 827 +/- 167 pg/mL [p = .10],
      monocyte chemotactic protein-1 6161 +/- 1302 vs. 3373 +/- 228 pg/mL [p = .03],
      interleukin-1beta 34 +/- 5 vs. 23 +/- 2 pg/mL [p < .01], C-reactive protein 39 +/
      4 vs. 29 +/- 2 mg/L [p = .02]). In contrast, release of the anti-inflammatory
      cytokine interleukin-10 was increased by C1-esterase inhibitor (peak level 73 +/-
      11 vs. 121 +/- 18 pg/mL, p = .02). The increase in interleukin-1 receptor
      antagonist tended to be smaller in the C1-esterase inhibitor group, but this
      effect did not reach statistical significance (p = .07). Markers for endothelial
      activation were increased after lipopolysaccharide infusion, but no significant
      differences between groups were observed. The lipopolysaccharide-induced changes
      in heart rate, blood pressure, body temperature, and symptoms (all p < .001 over
      time) were not influenced by C1-esterase inhibitor. Complement fragment C4 was
      not increased after lipopolysaccharide challenge. CONCLUSIONS: This study is the
      first to demonstrate that C1-esterase inhibitor exerts anti-inflammatory effects
      in the absence of classic complement activation in humans.

PMID- 20693887
TI  - Erythropoietin is equally effective as fresh-blood transfusion at reducing
      infarct size in anemic rats.
AB  - OBJECTIVE: We recently demonstrated that transfusion of anemic animals up to 100
      g/L hemoglobin with fresh blood protects the heart from ischemic injuries
      following myocardial infarction. Erythropoietin has cardioprotective effects
      independent of its erythropoietic activity. The objective of this study was to
      compare the cardioprotective effects of erythropoietin treatment to fresh-blood
      transfusion in anemic rats after acute myocardial infarction. DESIGN: Randomized
      animal study. SETTING: University laboratory. SUBJECTS: Male Sprague-Dawley rats
      weighing 200-300 g. INTERVENTION: Myocardial infarction was induced by coronary
      artery ligation in 76 rats, 55 of which were anemic (80-90 g/L) and 21 of which
      had normal hemoglobin levels. Animals were randomized to erythropoietin (2000
      units/kg), fresh-blood transfusion to 100 g/L hemoglobin, or saline-treatment
      groups immediately following myocardial infarction. MEASUREMENTS AND MAIN
      RESULTS: At 24 hrs after myocardial infarction, cardiac function and infarct size
      were determined. Myocardial apoptosis was determined by caspase-3 activity and
      terminal deoxynucleotidyl transferase d-UTP nick end labeling (TUNEL) assay.
      Infarct size was significantly decreased in anemic rats treated with
      erythropoietin or blood transfusion compared to those in the saline-treatment
      group. Cardiac function, as measured by maximal positive and minimal negative
      first derivatives of left ventricular pressure, was better preserved in the
      normal hemoglobin groups and the erythropoietin- or transfusion-treated anemic
      animals compared to saline-treated anemic animals. Myocardial caspase-3 activity
      and TUNEL-positive nuclei were significantly increased in anemic rats but were
      decreased by erythropoietin treatment or red blood cell transfusion. CONCLUSIONS:
      Erythropoietin treatment is equally effective as fresh-blood transfusion in
      anemic rats after acute myocardial infarction at reducing infarct size,
      myocardial apoptosis, and improving cardiac function.

PMID- 20693888
TI  - The effects of epinephrine on outcomes of normothermic and therapeutic
      hypothermic cardiopulmonary resuscitation.
AB  - OBJECTIVE: To investigate the effects of epinephrine when administered during
      either normothermic or therapeutic hypothermic cardiopulmonary resuscitation on
      postresuscitation myocardial and cerebral function and survival. DESIGN:
      Prospective, randomized, placebo-controlled experimental study. SETTING:
      University-affiliated animal research laboratory. SUBJECTS: Thirty-two healthy
      male Sprague-Dawley rats. INTERVENTIONS: Ventricular fibrillation was induced and
      untreated for 8 mins. The animals were then randomly assigned to one of four
      groups: normothermic placebo control; normothermic epinephrine; hypothermic
      placebo control; and hypothermic epinephrine. Hypothermia was initiated
      coincident with the start of cardiopulmonary resuscitation. The blood temperature
      was reduced and maintained at 32 +/- 0.2 degrees C and continued for 4 hrs after
      resuscitation. Normothermic animals were maintained at 37 +/- 0.2 degrees C.
      Either placebo or epinephrine (20 MUg/kg) was administered 5 mins after the start
      of cardiopulmonary resuscitation and 3 mins before defibrillation. MEASUREMENTS
      AND MAIN RESULTS: Postresuscitation cardiac output, ejection fraction, and
      myocardial performance index were measured hourly for 4 hrs after resuscitation;
      neurologic deficit scores were measured daily for 7 days, and durations of
      survival were observed for up to 3 mos. Except for three normothermic control
      animals, all animals were resuscitated. When epinephrine was administered during
      normothermic cardiopulmonary resuscitation, postresuscitation myocardial function
      was severely impaired when compared with the normothermic control group. However,
      postresuscitation myocardial function was significantly better in animals treated
      with epinephrine during hypothermic cardiopulmonary resuscitation when compared
      with hypothermic controls. This was associated with significantly fewer
      postresuscitation ventricular arrhythmias, less ST-segment elevation, better
      postresuscitation neurologic deficit scores, and longer duration of survival.
      CONCLUSIONS: Epinephrine, when administered during normothermic cardiopulmonary
      resuscitation, significantly increases the severity of postresuscitation
      myocardial dysfunction and decreases the duration of survival. These detrimental
      effects of epinephrine, however, no longer exist when it is administered during
      therapeutic hypothermic cardiopulmonary resuscitation.

PMID- 20693889
TI  - Regional anesthesia and co-existing chronic pain.
AB  - PURPOSE OF REVIEW: Investigate the rational for incorporation of regional
      anesthesia techniques into a multimodal approach toward patients with co-existing
      chronic pain as increasing numbers of chronic pain patients are presenting for
      surgery. RECENT FINDINGS: There is a growing body of evidence suggesting that
      regional anesthesia may be superior to opioids for improved pain control along
      with increased patient satisfaction and decreased perioperative morbidity and
      mortality comparing to general anesthesia in patients with significant medical
      disease(s) and may also carry several economic benefits. Despite the prevalence
      of chronic pain and data suggesting that patients with chronic pain are prone to
      exacerbation of their condition(s) following surgery, regional anesthesia
      techniques for these patients is only beginning to be developed. SUMMARY: The
      systemic condition of chronic pain has important practical and clinical
      implications for regional anesthesia implementation by anesthesiologists and pain
      management physicians. Comprehensive preadmission assessment together with a
      complete medication history and close follow-up management should always be
      employed in patients with pre-existing chronic pain throughout the perioperative
      setting. Despite successful implementation of neural blockade, and to avoid
      opioid withdrawal, at least half the chronic pain patient's daily pre-admission
      opioid dose should be continued daily throughout the perioperative period.
      Regional anesthesia is a preferable anesthetic option for perioperative
      management technique of patients with co-existing chronic pain, even if it
      requires supplementation with sedation or general anesthesia. The specifics of
      regional anesthesia performance and practical strategies for regional anesthesia
      application in chronic pain patients, including implanted pain management
      devices, are reviewed in this study.

PMID- 20693890
TI  - Indications and management of continuous infusion of local anesthetics at home.
AB  - PURPOSE OF REVIEW: The review examines recent research activity in the field of
      continuous peripheral nerve blocks in the ambulatory setting and places it in
      context with regard to previous research efforts. RECENT FINDINGS: Use of
      continuous peripheral nerve blocks at home following outpatient surgery is an
      increasingly accepted form of anesthesia practice. Researchers continue active
      investigation of optimal strategies for the relationship between continuous local
      anesthetic infusion volume and concentration as well as assisted and ideal
      catheter placement techniques including ultrasound. SUMMARY: Continuous
      peripheral nerve blockade at home offers good short-term control of postoperative
      pain in the outpatient setting. Long-term outcomes remain to be evaluated fully.
      More information is becoming available on local anesthetic volume and
      concentration relationships in both the upper and lower extremities--optimal
      strategies are not yet clear. Ultrasound may offer benefits in terms of speed and
      ease of continuous catheter placement while reducing the necessary number of
      needle passes required to reach the target structure site(s).

PMID- 20693891
TI  - Update on mucosal immunoglobulin A in gastrointestinal disease.
AB  - PURPOSE OF REVIEW: To review recent findings dealing with the involvement of
      mucosal immunoglobulin A (IgA) in the gut barrier function and various
      gastrointestinal diseases. New information will be discussed in the context of
      previous knowledge in this field. RECENT FINDINGS: The epithelial barrier
      function seems to be central in many mucosal disorders because it is decisive for
      host-microbial interactions and penetration of soluble antigens into the lamina
      propria. Secretory IgA contributes to the barrier function and recent evidence
      strongly supports the notion that such antibodies are involved in immunological
      homeostasis. SUMMARY: Inflammatory bowel disease involves a break of tolerance to
      the commensal microbiota. Aberrations in the mucosal IgA system may, therefore,
      be part of the inflammatory bowel disease pathogenesis. In gluten-induced
      enteropathy, however, it has been suggested that a mucosal IgA response may
      promote the progression of celiac disease and dermatitis herpetiformis by
      enhancing the uptake of gluten peptides and inhibiting the enzyme activity of
      tissue transglutaminase. A mucosal IgA response may also promote gastritis by
      protecting Helicobacter pylori from complement attack. In food allergy, several
      facets of the epithelial barrier function may show deficiency, including
      secretory IgA.

PMID- 20693892
TI  - Paneth cells and innate mucosal immunity.
AB  - PURPOSE OF REVIEW: Recent evidence shows that disruption of Paneth cell
      homeostasis by induction of endoplasmic reticulum stress or autophagy, with
      consequent apoptosis, contributes to inflammation and morbidity in a variety of
      experimental mouse models. RECENT FINDINGS: Recent advances show that
      proinflammatory mediators in Paneth cell dense core secretory granules mediate
      tumor necrosis factor-alpha-induced shock, that Paneth cell alpha-defensins
      modulate the composition of the small intestinal microflora, that development of
      crypt organoid culture systems provides a novel means for investigating the crypt
      microenvironment, and that varied genetic defects that disrupt Paneth cell
      homeostasis are emergent as risk factors in inflammatory bowel disease. SUMMARY:
      This recent literature identifies Paneth cells as particularly sensitive targets
      of endoplasmic reticulum stress responses and implicates this unique small
      intestinal lineage in inflammatory bowel disease pathogenesis resulting from
      diverse heritable and environmental causes.

PMID- 20693893
TI  - Enhanced mucosal imaging.
AB  - PURPOSE OF REVIEW: The continued application of innovative imaging systems to
      endoscopic procedures has vastly improved the detection of indiscriminant tissue
      anomalies. This article describes the fundamental principles of these
      technologies and reviews the advances of each over the past 18 months,
      considering their utility in the diagnosis and surveillance of various
      gastrointestinal diseases. RECENT FINDINGS: Through a combination of novel
      optics, processors and filters, real-time high-resolution contrast endoscopy
      provides increased visual data without greater procedure duration or difficulty.
      Optical contrast techniques incorporated into endoscopes, such as narrow band
      imaging (Olympus), i-Scan (Pentax), and Fujinon Intelligent Chromo Endoscopy,
      have become standard of care for many endoscopists. These technologies, as well
      as autofluorescence imaging, potentially improve detection of mucosal
      abnormalities, serving as 'red flag' tools for the evaluation of wide areas of
      mucosa. In addition, a number of promising devices allow virtual histology and in
      vivo diagnosis, thereby directing biopsies and potentially guiding concurrent
      interventions. One such technology, confocal laser endomicroscopy, continues to
      establish its role in clinical practice. Because of inherent shortcomings
      affecting each modality's sensitivity and specificity, the coupling of various
      devices, as with endoscopic trimodal imaging, has shown great promise; however,
      most are not widely available and not definitively proven to be superior to more
      established techniques. Emerging technologies, including in-vivo molecular
      tagging, provide a powerful means of detecting disease without reliance on
      morphologic diagnostic criteria. SUMMARY: Endoscopy continues to evolve from a
      field that previously allowed only macroscopic imaging dependent on subsequent
      pathology to one that allows real-time in-vivo diagnosis. Although the promise of
      enhanced endoscopic technologies seems limitless, practical and technological
      considerations slow their adoption into the standard of care.

PMID- 20693894
TI  - Quality measures and credentialing in gastrointestinal endoscopy.
AB  - PURPOSE OF REVIEW: Quality assessment and improvement are now mainstream
      activities in medicine. This review presents recent publications pertaining to
      quality, proposed quality measures, and associated topics in credentialing and
      delivery of endoscopic services. RECENT FINDINGS: The literature continues to
      focus primarily on colonoscopy services. Surveillance colonoscopy continues to
      suffer from underuse in high-risk patients and overuse in average to moderate
      risk patients, based upon current guidelines for application. Several series
      update and add to our understanding of adenoma detection rates as measures of
      quality. One study confirmed an inverse association between adenoma detection
      rates at screening endoscopy and the risk for identification of colorectal cancer
      at a subsequent diagnostic or surveillance procedure. Credentialing guidelines
      proposed for worldwide application are becoming uniform and similar to those from
      several national societies. Quality measures for use in endoscopic
      ultrasonography and endoscopic retrograde cholangiopancreatography are just
      beginning to be assessed in large series. SUMMARY: Proposed quality measures for
      colonoscopy are maturing, with increasing emphasis on adenoma detection rates
      rather than indirect proxies for neoplasia detection. Personal and unit-based
      benchmarking appears to be gaining favor and is facilitated by use of automated
      reporting systems. Greater attention is being focused on individual performance
      and assuring competence of the endoscopy workforce.

PMID- 20693895
TI  - Natural orifice translumenal endoscopic surgery.
AB  - PURPOSE OF REVIEW: Since its introduction in 2000, natural orifice translumenal
      endoscopic surgery (NOTES) has gained a great deal of attention from
      gastroenterologists and surgeons all over the world. In this article, we will
      review the progress in the field of NOTES and present the latest publications
      that provide some answers and solutions to the barriers suggested by the Natural
      Orifice Surgery Consortium for Assessment and Research white paper. RECENT
      FINDINGS: Because of the first human NOTES procedure by Rao and Reddy, more
      pioneering procedures, including transgastric and transvaginal cholecystectomies,
      appendectomies, and hernia repairs, have been performed. Although NOTES
      researchers continue to experiment with new innovative equipment and procedures
      in the lab, more structured work, including randomized controlled trials, has
      been published. SUMMARY: In the last several years, there has been growing
      interest in NOTES, which has translated into exciting animal research work and
      publication of randomized controlled trials. Additionally, preliminary NOTES
      human procedures have been successfully performed. When suitable instruments
      become available, the subsequent step should be comparing NOTES with current
      laparoscopic approaches. Superiority or even equality of NOTES to laparoscopic
      surgery would be the best argument for advancing and integrating implementation
      into clinical practice.

PMID- 20693896
TI  - Chronic pancreatitis.
AB  - PURPOSE OF REVIEW: We review important new clinical observations in chronic
      pancreatitis made in the past year. RECENT FINDINGS: Cigarette smoking is a dose
      dependent risk factor for acute pancreatitis, recurrent acute pancreatitis, and
      chronic pancreatitis. A minority of chronic alcohol consumers develop recurrent
      acute pancreatitis but very heavy drinking associates with chronic pancreatitis.
      More patients with alcohol-induced chronic pancreatitis have cirrhosis than
      patients with cirrhosis have chronic pancreatitis (39 vs. 18%). Most patients
      with asymptomatic hyperenzymemia have no pancreatic lesions. Pancreatic
      calcifications are most frequently due to chronic pancreatitis, followed by
      cystic neoplasms and other disorders. The new Rosemont consensus classification
      of endoscopic ultrasonography criteria for chronic pancreatitis is unvalidated.
      Zinc deficiency correlates only with severe chronic pancreatitis and the fecal
      elastase test is an inaccurate marker of pancreatic steatorrhea. Patients
      commonly receive insufficient lipase to abolish pancreatic steatorrhea.
      Ultrastructural neuropathies are common to chronic pancreatitis and pancreatic
      cancer and correlate with pain severity. SUMMARY: Results of this year's
      investigations further elucidated risk factors for pancreatic disease, the
      natural history of alcoholic pancreatitis, the differential diagnosis of
      pancreatic calcifications, the diagnosis of chronic pancreatitis with the
      Rosemont criteria, the limited diagnostic utility of fecal elastate test and zinc
      measurements, the proper dosing of pancreatic enzyme supplements, and treatment
      of pancreatic pain.

PMID- 20693897
TI  - Diagnosis and treatment of autoimmune pancreatitis.
AB  - PURPOSE OF REVIEW: To summarize the existing knowledge of autoimmune pancreatitis
      (AIP) and to review the progress made in the diagnosis and treatment of AIP in
      the past year. RECENT FINDINGS: The term 'AIP' appears to encompass at least two
      distinct subtypes, type 1 and type 2. Type 1 AIP is the pancreatic manifestation
      of a systemic fibroinflammatory disease called immunoglobulin G4-associated
      systemic disease. Type 2 AIP affects younger patients, does not have a gender
      predilection and is associated with normal serum immunoglobulin G4 levels.
      Existing criteria are geared toward diagnosis of type 1; type 2 AIP can be
      definitively diagnosed only on pancreatic histology. Both subtypes respond to
      corticosteroid therapy. However, there are no standardized protocols for initial
      treatment or management and prevention of relapses in AIP. A novel antibody for
      AIP has recently been identified and its performance needs validation from other
      centers. Newly published strategies for differentiating AIP from pancreatic
      cancer are available. SUMMARY: AIP is a rare disease whose recognition and
      understanding are evolving. Much needs to be elucidated with regard to its cause,
      pathogenesis, treatment of relapse and long-term outcomes. A multidisciplinary
      team, familiar with the disease, is critical in making the correct diagnosis.

PMID- 20693898
TI  - The contribution of airway and lung tissue ischemia to primary graft dysfunction.
AB  - PURPOSE OF REVIEW: Primary graft dysfunction (PGD) is the primary obstacle to
      short-term survival for post-lung transplant patients. PGD is a form of acute
      lung injury secondary to donor brain death and ischemia-reperfusion damage to the
      allograft affecting 10-25% of all lung transplant recipients. This article
      reviews the significant role of allograft ischemia in the phenotypic presentation
      of PGD and the evidence for activation and disruption of normal cellular pathways
      for the development and long-term sequelae. RECENT FINDINGS: Pathways implicated
      in the pathogenesis of PGD resultant from tissue ischemia include abnormalities
      in coagulation and fibrinolysis, epithelial cell injury, endothelial cell
      dysfunction, chemotaxis, and alterations in cell adhesion. Blood and
      bronchoalveolar lavage fluid biomarkers from these pathways have been
      increasingly identified as useful for diagnosing and predicting the development
      of severe PGD. SUMMARY: Future efforts at preventing and treating severe PGD
      should focus on techniques for altering the pathways involved in PGD
      pathogenesis. Ex-vivo lung perfusion and transduction with interleukin-10 are
      promising modalities for preventing PGD and expanding the available lung
      transplant donor pool.

PMID- 20693899
TI  - The contribution of airway ischemia and vascular remodelling to the
      pathophysiology of bronchiolitis obliterans syndrome and chronic lung allograft
      dysfunction.
AB  - PURPOSE OF REVIEW: Chronic allograft dysfunction continues to limit the enduring
      success of lung transplantation. Increasingly it is recognized that events very
      early post-transplant such as primary graft dysfunction can be linked to poor
      clinical outcomes at much later time points. In this article we review a number
      of the different processes that predispose the allograft to ischemia early post
      transplant and explore how these events may contribute to obliterative
      bronchiolitis, the histological correlate of chronic lung allograft dysfunction.
      RECENT FINDINGS: Allograft ischemia may arise during explantation (warm
      ischemia), at implantation (in the absence of bronchial arterial reanastomosis)
      or at later time points (small airway microvascular damage). We describe how
      allograft ischemia may result in a hypoxic inflammatory milieu within the lung
      allograft that is conducive to vascular remodelling and angiogenesis. SUMMARY:
      Whilst the published literature for vascular remodelling in post-transplant
      obliterative bronchiolitis is not as extensive as that for asthma, a disease also
      characterized by airway pathology, there are clear parallels and shared
      pathophysiological pathways between the two diseases. An understanding of the
      complex interaction between ischemia, vascular remodelling and chronic lung
      allograft dysfunction may lead to the future development of therapeutic
      strategies that can unravel this association.

PMID- 20693901
TI  - Mechanisms of vestibular compensation: recent advances.
AB  - PURPOSE OF REVIEW: This article reviews recent studies that have provided
      experimental evidence for mechanisms of neural and synaptic plasticity in the
      brain during vestibular compensation, the behavioural recovery that takes place
      following peripheral vestibular lesions. RECENT FINDINGS: First, experimental
      evidence from animal studies indicates that an unbalanced vestibular commissural
      system is a fundamental cause of the syndrome of oculomotor and postural deficits
      after unilateral labyrinthectomy. Second, recent studies suggest the involvement
      of both GABAergic and glycinergic commissural neurons. In addition gliosis and
      reactive neurogenesis in the ipsilesional vestibular nuclei appear to be involved
      in compensation. Third, evidence from cerebellar-deficient mutant mice
      demonstrates an important role for cerebellum-dependent motor learning in the
      longer term. Factors such as stress steroids and neuromodulators such as
      histamine influence these plasticity mechanisms and may thus contribute to the
      development of compensation in patients. SUMMARY: Vestibular compensation
      involves multiple, parallel plastic processes at various sites in the brain.
      Experimental evidence suggests that adaptive changes in the sensitivity of
      ipsilesional vestibular neurons to the inhibitory neurotransmitters GABA and
      glycine, changes in the electrophysiological excitability of vestibular neurons,
      changes in the inhibitory control of the brainstem vestibular networks by the
      cerebellum, gliosis and neurogenesis in the ipsilesional vestibular nuclei, and
      activity-dependent reorganization of the synaptic connectivity of the vestibular
      pathways are mechanisms involved in compensation.

PMID- 20693900
TI  - Ion homeostasis in the ear: mechanisms, maladies, and management.
AB  - PURPOSE OF REVIEW: To describe ion and water homeostatic mechanisms in the inner
      ear, how they are compromised in hearing disorders, and what treatments are
      employed to restore auditory function. RECENT FINDINGS: The ion and water
      transport functions in the inner ear help maintain the proper endolymph K
      concentration required for hair cell function. Gene defects and idiopathic
      alterations in these transport functions cause hearing loss, but often the
      underlying cause is unknown. Current therapies largely involve glucocorticoid
      treatment, although the mechanisms of restoration are often undeterminable.
      Recent studies of these ion homeostatic functions in the ear are characterizing
      their cellular and molecular control. It is anticipated that future management of
      these hearing disorders will be more targeted to the cellular processes involved
      and improve the likelihood of hearing recovery. SUMMARY: A better understanding
      of the ion homeostatic processes in the ear will permit more effective management
      of their associated hearing disorders. Sufficient insight into many homeostatic
      hearing disorders has now been attained to usher in a new era of better therapies
      and improved clinical outcomes.

PMID- 20693902
TI  - Cochlear otosclerosis.
AB  - PURPOSE OF REVIEW: The aim of this study is to summarize current advances in
      research and clinical aspects of cochlear otosclerosis. RECENT FINDINGS: Recent
      studies have revealed that otosclerosis is a process of bone remodeling that is
      unique to the otic capsule only. Even though no obvious bone remodeling is seen
      in the otic capsule under normal conditions, remodeling starts when some
      molecular factors trigger the capsule in certain patients who have genetic and/or
      environmental tendencies. SUMMARY: Cochlear otosclerosis is defined as
      otosclerosis located in the otic capsule involving the cochlear endosteum and
      causing sensorineural hearing loss or mixed-type hearing loss. It has been
      clearly shown that, when otosclerosis is sufficiently severe to involve the
      cochlear endosteum, it usually fixes the stapes as well.

PMID- 20693903
TI  - Role of diet in the development of immune tolerance in the context of allergic
      disease.
AB  - PURPOSE OF REVIEW: Diet is arguably one of the most significant environmental
      exposures during early development. Here, we explore the effects of key perinatal
      dietary exposures on immune development and susceptibility to allergic disease.
      RECENT FINDINGS: Dietary changes are at the centre of the emerging epigenetic
      paradigms that underpin the rise in many modern diseases. There is growing
      evidence that exposures in pregnancy and the early postnatal period can modify
      gene expression and disease susceptibility. Specific nutrients, including
      antioxidants, oligosaccharides, polyunsaturated fatty acids, folate and other
      vitamins, have documented effects on immune function. Some have also been
      implicated in modified risk of allergic disease in observational studies.
      Intervention studies are largely limited to trials with polyunsaturated fatty
      acids and oligosaccharides, showing preliminary but yet unconfirmed benefits in
      allergy prevention. Avoidance of food allergens in pregnancy, lactation or
      infancy has provided no clear evidence in allergy prevention and is no longer
      recommended. Rather there is focus on their role in tolerance induction. SUMMARY:
      Modern dietary changes are clearly implicated in the rising propensity for
      inflammatory immune responses. These dietary changes, which appear to be
      providing less tolerogenic conditions during early immune programming, may
      provide important avenues for preventing disease.

PMID- 20693904
TI  - Overcoming barriers to breastfeeding continuation and exclusivity.
AB  - PURPOSE OF REVIEW: To review recent research that delineates predictors of
      breastfeeding duration and exclusivity. RECENT FINDINGS: Many mothers find it
      difficult to meet personal goals and follow expert recommendations for continued
      and exclusive breastfeeding despite increased rates of initiation. Recent studies
      have revealed varied sociodemographic, biomedical, and psychosocial determinants
      of breastfeeding duration and exclusivity. SUMMARY: In order to help mothers meet
      personal goals and expert recommendations for breastfeeding, pediatricians should
      educate themselves regarding predictors of and barriers to successful
      breastfeeding. Once these predictors and barriers have been identified, targeted
      anticipatory guidance can be provided to help mothers achieve breastfeeding
      success.

PMID- 20693906
TI  - Recent advances in pulmonary fibrosis: implications for scleroderma.
AB  - PURPOSE OF REVIEW: The term 'pulmonary fibrosis' encompasses a heterogeneous
      group of disorders characterized by replacement of the lung parenchyma with scar
      tissue. Despite many years of research, its pathogenesis remains obscure and a
      cure remains elusive. The bulk of human data in this area derive from patients
      with idiopathic pulmonary fibrosis. Pulmonary fibrosis has also emerged as a
      leading cause of mortality in patients with systemic sclerosis. Because of a lack
      of effective therapy, better understanding of the mechanism(s) driving this
      disease has the potential to impact the proximate cause of death in most patients
      with scleroderma. RECENT FINDINGS: Animal modeling and translational human
      studies lend insight into the pathogenesis of lung fibrosis. Recent developments
      include the role of epithelial cell injury, endoplasmic reticulum stress and Wnt
      signaling, the contributions of alternatively activated macrophages and
      efferocytosis, the extra-mesenchymal origin of fibroblasts including epithelial
      mesenchymal transition and fibrocytes, a possible association with senescence and
      aging, and the emerging role of lymphocytes in the fibrotic response. SUMMARY:
      Novel investigations defining the mechanism of epithelial cell injury,
      alternative macrophage activation and efferocytosis, alternate sources of
      fibroblasts, cellular senescence, and lymphocyte function may lend new insight
      into the pathogenesis of scleroderma-related pulmonary fibrosis.

PMID- 20693905
TI  - Peroxisome proliferator-activated receptor gamma: innate protection from
      excessive fibrogenesis and potential therapeutic target in systemic sclerosis.
AB  - PURPOSE OF REVIEW: Progressive organ fibrosis and pulmonary arterial hypertension
      (PAH) are the leading causes of death in patients with systemic sclerosis (SSc).
      However, the pathogenesis and the link between these two processes remain
      obscure. A better understanding of these events is needed in order to facilitate
      the discovery and development of effective therapies for SSc. RECENT FINDINGS:
      Recent reports provide evidence that the orphan receptor peroxisome proliferator
      activated receptor gamma (PPARgamma), better known for its pivotal role in
      metabolism, has potent effects on inflammation, fibrogenesis and vascular
      remodeling and is important in the pathogenesis of fibrosis and PAH, and as a
      potential therapeutic target in SSc. The studies discussed in this review
      indicate that ligands of PPARgamma potently modulate connective tissue turnover
      and suggest that aberrant expression or function of PPARgamma is associated with,
      and very likely contributes to, the progression of pathological fibrosis and
      vascular remodeling. These observations are of particularly relevance because FDA
      approved drugs of the thiazolidinedione class currently used for the treatment of
      obesity-associated type 2 diabetes activate PPARgamma signaling. Moreover, novel
      PPARgamma ligands with selective activity are under development or in clinical
      trials for inflammatory diseases, asthma, Alzheimer disease and cancer. SUMMARY:
      Drugs targeting the PPARgamma pathway might be effective for the control of
      fibrosis as well as pathological vascular remodeling underlying PAH and,
      therefore, might have a therapeutic potential in SSc. A greater understanding of
      the mechanisms underlying the antifibrogenic and vascular remodeling activities
      of PPARgamma ligands will be necessary in order to advance these drugs into
      clinical use.

PMID- 20693907
TI  - Contribution of anorexia to tissue wasting in cachexia.
AB  - PURPOSE OF REVIEW: Anorexia is a severe debilitating symptom characterizing the
      clinical course of several chronic diseases. It negatively impacts on patient
      outcome by contributing to weight loss, lean body mass catabolism and adipose
      tissue wasting. Although disease-associated anorexia may stand alone as a
      clinically relevant symptom, it is now considered as a component of the cachexia
      syndrome. The present review discusses experimental and clinical data indicating
      that the pathogenic mechanisms of anorexia may also suggest a neural control of
      tissue wasting in cachexia. RECENT FINDINGS: Consistent data show that selective
      melanocortin receptor antagonism modulates food intake and reduces wasting in
      experimental models of chronic disease. Consequently, ghrelin administration,
      whose prophagic effects are related to melanocortin antagonism, has been tested
      both in animal studies and human trials, with promising effects, although
      restoration of lean body mass has been not achieved. More interest is driven by
      the use of small molecules selectively antagonising hypothalamic melanocortin
      receptors. SUMMARY: The 'brain-muscle axis' coordinated by the hypothalamus seems
      to mediate the onset of not only anorexia but also tissue wasting in cachexia, by
      centrally influencing energy homeostasis and the balance between anabolism and
      catabolism.

PMID- 20693908
TI  - Hydration in cancer patients.
AB  - PURPOSE OF REVIEW: To provide an overview of issues central to hydration in an
      oncology population while highlighting recent advances and publications in the
      clinical and scientific literature. RECENT FINDINGS: Dehydration accounts for a
      significant number of unplanned visits to cancer clinics and emergency rooms. The
      decision to provide or withhold fluid in patients with terminal cancer is
      strongly influenced by subjective beliefs and the decision to use of hydration at
      the end of life should be individualized. Chronic dehydration may play a role in
      the pathogenesis of cancer. SUMMARY: Cancer patients are at high risk for
      dehydration from both the disease and the treatment. Treating physicians should
      have a low threshold for providing additional fluids to prevent dehydration. For
      patients at the end of life, hydration may be indicated in select patients.

PMID- 20693909
TI  - Body cooling ameliorating spinal cord injury may be neurogenesis-, anti
      inflammation- and angiogenesis-associated in rats.
AB  - BACKGROUND: Body cooling (BC) or mild hypothermia therapy (about 33 degrees C) is
      reportedly effective for spinal cord injury (SCI). However, the mechanisms
      underlying the beneficial effects of BC remain unclear, so does BC ameliorating
      SCI via promoting neurogenesis, anti-inflammation, and angiogenesis. METHODS: The
      standard rat compression SCI model was tested hypothetically in two groups: one
      receiving BC (33 degrees C) and the other, normothermia (37 degrees C).
      Afterward, the effects of BC therapy on the hind limb locomotion, spinal cord
      infarction and apoptosis, angiogenesis, neurogenesis, and inflammation in these
      two groups of SCI were assessed. The other group of sham SCI was used as
      controls. RESULTS: Apoptosis (evidenced by higher numbers of terminal
      deoxynucleotidyl- transferase-mediated and duDP-biotin nick end-labeling-positive
      cells), infarct, activated inflammation (evidenced by higher levels of tumor
      necrosis factor-alpha, interleukin-1beta, and myeloperoxidase), and hind limb
      locomotor dysfunction were inspected in the untreated (37 degrees C) SCI rats 4
      days after SCI. When compared with those of untreated SCI rats, SCI rats
      receiving BC (33 degrees C) displayed lower levels of apoptosis, infarct volume,
      activated inflammation, and hind limb locomotor dysfunction. In addition, that BC
      promoted both angiogenesis (evidenced by increased numbers of both vascular
      endothelial growth factors and bromodeoxyuridine-positive endothelial cells) and
      neurogenesis (evidenced by increased numbers of both glial cell line-derived
      neurotrophic growth factors and bromodeoxyuridine-neuronal-specific nuclear
      protein double positive cells) in the injured spinal cord was evaluated 4 days
      after SCI. CONCLUSION: BC (33 degrees C) improved SCI outcomes by promoting
      angiogenesis, neurogenesis, and anti-inflammation in a rat SCI model.

PMID- 20693910
TI  - Caveolin-1 siRNA increases the pulmonary microvascular and alveolar epithelial
      permeability in rats.
AB  - BACKGROUND: Increased pulmonary microvascular and epithelial permeability are
      important contributors to pulmonary edema in acute lung injury. In this study, we
      used small interfering RNA (siRNA) to knock down caveolin-1 expression in rat
      lungs and to confirm the important role of caveolin-1 in regulating pulmonary
      edema. METHOD: After pulmonary injection of siRNA against caveolin-1 messenger
      RNA incorporated in liposomes with three concentrations of 0.4, 0.8, and 1.2
      mg/kg, the gene silencing rate and the effects of caveolin-1 siRNA on aquaporin
      (AQP)-1, AQP-5, and epithelial sodium channel (ENaC) were detected. For pulmonary
      permeability analysis, Evans blue fluorimetry, ratios of albumin concentrations
      between blood and bronchoalveolar lavage, and wet/dry weight ratios were
      measured. The impacts of caveolin-1 suppression on interendothelial junctions
      were evaluated by the performance of electron microscopy and the analysis of
      vascular endothelial (VE)-cadherin Western blot. Alveolar wall thickness analysis
      and chest fluoroscopy were performed to determine the pulmonary edema degree.
      RESULTS: After 72 hours of injection, the gene silencing rate of caveolin-1 siRNA
      is about 87%. AQP-1, AQP-5, ENaC-alpha, ENaC-beta, ENaC-gamma, and VE-cadherin
      protein levels were decreased by 63%, 66%, 80%, 90%, 89%, and 50%, respectively.
      Caveolin-1 siRNA also resulted in increasing microvascular and epithelial
      permeability and pulmonary edema. CONCLUSION: These data suggest that caveolin-1
      plays an important part in regulating the pulmonary permeability by modifying AQP
      1, AQP-5, ENaC, and VE-cadherin.

PMID- 20693911
TI  - Neurological and functional recovery in multiple injured patients with
      paraplegia: outcome after 1 year.
AB  - BACKGROUND: Injuries of thoracic vertebrae in multiple trauma patients are often
      accompanied by severe thoracic injuries and sensorimotor deficits. However, until
      now, it is not clear whether and how the severity of trauma influences the
      neurologic and functional outcome in paraplegic patients during the first year
      after the trauma. The aim of the study was to compare two cohorts of multiple
      injured paraplegic patients with and without conversion in the American Spinal
      Injury Association Impairment Scale (AIS) with regard to the severity of spinal
      trauma, the severity of thorax trauma, the type of fracture, and the functional
      outcome 1 year after the date of injury. METHODS: Twenty-one traumatic paraplegic
      patients (neurologic level T1-T12) were included in the study based on a
      retrospective analysis of the Heidelberg European Multicenter Study about Spinal
      Cord Injury database (www.emsci.org) from 2002 to 2007. In all patients, the
      Polytraumaschluessel (PTS), the AO classification, the AIS, and the Spinal Cord
      Independence Measure were collected. Patients with no change in the AIS (group 1,
      n=14) were compared with patients with AIS changes (group 2, n=7), and t test and
      chi test were performed (p<0.05). RESULTS: Differences in both groups concerning
      fracture classification were confirmed (p=0.046). A relation between neurologic
      improvement in the AIS and the severity of trauma (p=0.058) after 1 year was not
      found. The subitem PTST in the thoracic area showed statistical significance
      comparing the two groups (p=0.005). Both groups significantly improved
      functionally (Spinal Cord Independence Measure, p=0.035) during the first year
      but with no significant difference between the groups after 1 year. CONCLUSIONS:
      Our data suggest that functional improvement is achieved independently from
      neurologic recovery. The combined assessment of the PTS, the AO classification,
      and the AIS in multiple-injured paraplegic patients can contribute to provide a
      better prognostication of the neurologic changes during rehabilitation and the
      outcome after 1 year than the AIS alone.

PMID- 20693912
TI  - Altered expression of the microRNAS and their potential target genes in the
      soleus muscle after peripheral denervation and reinnervation in rats.
AB  - BACKGROUND: To profile the expression of microRNAs (miRNAs) and their potential
      target genes in the soleus muscles after denervation and reinnervation of the
      sciatic nerve in rats. MATERIALS AND METHODS: The 4 months denervated and
      reinnervated soleus muscles were analyzed with Agilent Rat miRNA array to detect
      the expressed miRNAs against those from the sham control. These differentially
      expressed miRNAs were applied for hierarchical cluster analysis using average
      linkage and Pearson correlation as a measure of similarity. A combined approach
      using computational prediction by the miRanda algorithm and the Agilent Whole Rat
      Genome 4* 44K oligo microarray experiment was performed to identify the potential
      target genes of these up-regulated miRNAs. Gene ontology (GO) analysis of these
      potential target genes into one of the three ontologies, biological process,
      molecular function, or cellular component, was performed and compared between the
      denervated and reinnervated muscles. RESULTS: Thirty-six and 39 miRNAs of 350 rat
      miRNAs tested were significantly up-regulated in the denervated and reinnervated
      muscles, respectively. The expressed miRNAs in these two groups were similar but
      with different folds, and the unsupervised hierarchy clustering was able to
      separate the samples into denervation and reinnervation groupings. In the GO
      analysis, all three categories indicated a considerable reduced number of the
      potential target genes of the up-regulated miRNAs and less fraction of
      differentially expressed genes in most of the GO terms in the reinnervated
      muscle. CONCLUSIONS: This study demonstrated a different involvement of miRNAs
      and their potential target genes in the soleus muscle after denervation and after
      reinnervation of the sciatic nerve in a rat model.

PMID- 20693913
TI  - Incidence and predictors of intracranial hemorrhage after minor head trauma in
      patients taking anticoagulant and antiplatelet medication.
AB  - BACKGROUND: The yield of head computed tomography (CT) for patients who suffered
      head trauma with a presenting Glasgow Coma Scale (GCS) score of 15 has been
      reported to be low, even in patients who are anticoagulated or on antiplatelet
      therapy. We undertook this study to (1) determine the frequency of intracranial
      hemorrhage in anticoagulated patients and patients on antiplatelet therapy and
      its impact on clinical management, (2) identify predictors of positive imaging
      findings, and (3) assess potential differences between anticoagulation and
      antiplatelet therapy. METHODS: We conducted a retrospective review of the trauma
      registry at our institution, a Level II trauma center. All trauma registry
      patients with a minor head injury registered between the years 2004 and 2006 who
      were taking warfarin or clopidogrel, had a presenting GCS score of 15, and
      underwent head CT were included in this study. Intracranial hemorrhage on head CT
      was considered a positive result. RESULTS: One hundred forty-one patients (male,
      n=67; female, n=74), mean age 79 years (range, 36-101 years), were included in
      this study. Forty-one patients (29%) were diagnosed with intracranial hemorrhage.
      Thirty-nine (95%) of these 41 patients underwent reversal and/or discontinuation
      of clopidogrel and/or warfarin. Five patients required surgical evacuation of an
      intracranial hemorrhage. Four patients died. Loss of consciousness (Wald=7.468,
      beta=1.179, p=0.008) predicted a positive CT result. Type of medication
      (warfarin, aspirin, or clopidogrel) did not reach statistical significance as a
      predictor of positive result. CONCLUSION: Despite a presenting GCS score of 15,
      patients with minor head injury from the trauma registry at our institution
      taking anticoagulation or antiplatelet therapy have a high incidence of
      intracranial hemorrhage especially after reported loss of consciousness.

PMID- 20693914
TI  - Mortality after thermal injury: no sex-related difference.
AB  - BACKGROUND: Young women have been reported to be more likely to survive than men
      after severe trauma. Girls also have less inflammation and hypermetabolism after
      major burns. Yet burned women have been found to have a twofold greater risk of
      death than men. Our aim was to find out if there is a sex-related difference in
      mortality after thermal injury, particularly in the age group between 16 years
      and 49 years, when hormonal differences would be most influential. METHODS: All
      patients admitted to the Linkoping University Hospital Burn Unit with thermal
      injuries during the years 1993-2008 were included and the variables percentage
      burned total body surface area (TBSA%), age, type of burn, mechanical
      ventilation, and year were included in a multiple regression (Poisson log) model.
      RESULTS: Of 1,119 patients with thermal injury, 792 (71%) were men. Crude
      mortality was 5% among men, and 8% among women (p = 0.04). After adjustment for
      age and TBSA%, there was no correlation between mortality and sex, in any age
      group. Eight men and four women died in the group of young adults (16-49 years)
      in which TBSA% correlated with mortality (p < 0.01) but age did not. Mortality
      was 14% (32 of 221) among the men and 23% (23 of 102) of women in the group of
      older adults (50 years and older), and both age and TBSA% correlated with
      mortality (p < 0.001). CONCLUSIONS: There is no relevant sex-related difference
      in survival after thermal injury. The conclusion is, however, tempered by the few
      deaths, particularly among younger adults.

PMID- 20693915
TI  - Prevalence of posttraumatic stress disorder and major depression after trauma
      center hospitalization.
AB  - BACKGROUND: Individuals hospitalized after physical trauma are at heightened risk
      for mental disorders. We examined prevalence rates of both posttraumatic stress
      disorder (PTSD) and major depression at 6 and 12 months in a sample of 677
      individuals experiencing different types of trauma who were representative of
      physical trauma survivors hospitalized in Los Angeles County trauma centers.
      Demographic and injury-related risk factors for these disorders were also
      evaluated. METHODS: Bivariate logistic regressions estimated risk for PTSD and
      depression at either 6 or 12 months associated with baseline risk factors.
      RESULTS: At 6 months, 31% of participants met screening criteria for probable
      PTSD and 31% met criteria for probable depression. At 12 months, 28% and 29% met
      criteria for PTSD and depression, respectively. There were also high rates of
      comorbidity; depression and PTSD co-occurred in 21% of individuals at 6 months
      and in 19% of patients at 12 months. Bivariate logistic regressions indicated
      that preexisting disability and lower education were associated with higher odds
      of PTSD at either 6 or 12 months. African Americans and Hispanics had higher odds
      of PTSD compared with non-Hispanic Caucasians. Assault-related injury (versus
      accident), more severe injury, and longer hospitalizations were also associated
      with greater odds of PTSD. By contrast, higher odds of depression at 6 or 12
      months were only associated with preexisting disability, losing consciousness,
      more severe injury, and longer hospitalizations. CONCLUSIONS: Key demographic and
      injury characteristics may enhance identification of at-risk trauma survivors who
      would benefit from targeted screening, patient education, and early intervention
      efforts.

PMID- 20693916
TI  - Results of dynamic treatment of fractures of the proximal phalanx of the hand.
AB  - BACKGROUND: The treatment of fractures of the proximal phalanx in three-phalanx
      fingers has for a long time been the domain of conservative static treatment in a
      plaster cast. After removal of the plaster, there was usually limitation of
      mobility of the interphalangeal joints. Fractures of the proximal phalanx are
      managed with conservative functional treatment in our clinic. The aim of this
      method is to achieve bony healing and free mobility at the same time and not in
      succession. We evaluated our treatment outcomes in a follow-up study. METHODS:
      The dressing consists of a dorsopalmar plaster splint and a so-called finger
      splint. The wrist and metacarpophalangeal joints are immobilized with the plaster
      cast. The wrist is dorsiflexed 30 degrees, and the metacarpophalangeal joints are
      flexed 70 degrees to 90 degrees. In this intrinsic plus position, the extensor
      aponeurosis is taut and covers two-thirds of the proximal phalanx, thus leading
      to firm splinting of the fracture. RESULTS: Sixty-five patients (46 men and 19
      women) with 78 proximal phalanx fractures were followed up after an average of 23
      months (12-69 months). The average age of the patients was 41 years (18-93
      years). Among our patients, the ring finger was affected most often, with
      transverse fractures predominating. As regards the location, fractures in the
      proximal third were most frequent (51%). All fractures consolidated. Delayed
      fracture healing or pseudarthrosis was not observed. Sixty-seven fingers (86%)
      showed full range of motion at follow-up. In 11 cases (14%), there was limitation
      of finger joint movements, with inhibition of extension of the proximal
      interphalangeal joint in nine patients up to a maximum of 20 degrees. Two
      patients had limitation of flexion with a fingertip-palm distance of 1.1 cm.
      CONCLUSION: The aim of functional treatment of proximal phalanx fractures is to
      achieve bony healing and free mobility at the same time and not in succession.
      Active exercises in the proximal and distal interphalangeal joints prevent
      limitations of mobility and the subsequent occurrence of rotational and axial
      deformities.

PMID- 20693917
TI  - Revision internal fixation and nonvascular fibular graft for femoral neck
      nonunion.
AB  - BACKGROUND: The rates of nonunion after internal fixation for femoral neck
      fractures have been reported to range from 0% to 59%. Existing treatment options
      are osteotomy (with or without graft), osteosynthesis using various implants and
      grafting techniques (muscle pedicle, vascularized, and nonvascularized fibula),
      or arthroplasty. The objective of this study was to assess the outcome results of
      revision internal fixation and nonvascular fibular bone grafting for symptomatic
      aseptic femoral neck nonunion. METHODS: This is a retrospective case series study
      involving 17 patients with symptomatic femoral neck nonunion that were treated
      with revision internal fixation and fibular bone graft. The inclusion criteria
      were aseptic symptomatic femoral neck nonunion with no or minimal varus
      alignment. There were eight men and nine women. The average age was 46 years
      (range, 24-58 years). Thirteen patients had autogenous fibular bone graft, and
      six patients had fibular allograft. RESULTS: Of the 13 patients who had
      autogenous nonvascularized fibular bone grafts, four remained in nonunion.
      Fibular autograft had a 69.2% success rate with the mean time to union 4.8
      months. Four of the six patients who had fibular allografts remained in nonunion.
      Fibular allograft had a 33.3% success rate with the mean time to union 13.3
      months. CONCLUSION: This study showed that revision internal fixation and fibular
      autograft have resulted into a better and faster union rate than fibular
      allografts.

PMID- 20693918
TI  - Mitigating effects of captopril and losartan on lung histopathology in a rat
      model of fat embolism.
AB  - BACKGROUND: Fat embolization (FE) is an often overlooked and poorly understood
      complication of skeletal trauma and some orthopedic procedures. Fat embolism can
      lead to major pulmonary damage associated with fat embolism syndrome (FES).
      METHODS: A model of FE in unanesthetized rats, using intravenous injection of the
      neutral fat triolein, was used to study the potential therapeutic effect on lung
      histopathology of altering the production of, or response to, endogenous
      angiotensin (Ang) II. Either captopril, an Ang I converting enzyme inhibitor, or
      losartan, an Ang II type 1 receptor blocker, was injected 1 hour after FE by
      triolein injection. After euthanasia at 48 hours, histopathologic evaluation was
      used to compare the drug-treated animals with control animals that received only
      triolein. RESULTS: Histology of the lungs of rats treated only with triolein
      revealed severe, diffuse pathology. Alveolar septa showed severe, diffuse
      inflammation. Bronchial lumina showed severe mucosal epithelial loss. The media
      of the pulmonary small arteries and arterioles was thicker, and the lumen patency
      was reduced 60% to 70%. Trichrome staining confirmed the abundant presence of
      collagen in the media and adventitia, as well as collagen infiltrating the
      bronchial musculature. Both captopril and losartan treatments reduced the
      inflammatory, vasoconstrictor, and profibrotic effects present at 48 hours
      (p<0.001). With treatment, the vascular lumen remained patent, and the fat
      droplets were reduced in size and number. There was a reduction in the number of
      infiltrating leukocytes, macrophages, myofibroblasts, and eosinophils, along with
      a significant decrease in hemorrhage and collagen deposition (p<0.001).
      Pathologic changes in bronchial epithelium were also diminished. CONCLUSIONS: The
      results suggest that the use of drugs that act on the renin-Ang system might
      provide an effective and targeted therapy for fat embolism syndrome.

PMID- 20693919
TI  - Carbon monoxide-releasing molecule-2 enhances coagulation and diminishes
      fibrinolytic vulnerability in diluted plasma in vitro.
AB  - BACKGROUND: A carbon monoxide-releasing molecule (tricarbonyldichlororuthenium
      (II) dimer; CORM-2) enhances coagulation and attenuates vulnerability to
      fibrinolysis in normal and hemophiliac human plasma. We tested the hypothesis
      that plasma diluted with resuscitative fluids would demonstrate improved
      coagulation and decreased fibrinolytic vulnerability after exposure to CORM-2.
      METHODS: Normal, platelet-poor plasma was diluted 0%, 20%, 30%, 40%, or 50% with
      0.9% NaCl (NS) or low-molecular-weight hydroxyethyl starch (VOL) and,
      subsequently, exposed to 0 MUmol/L or 100 MUmol/L CORM-2 before activation with
      tissue factor (n = 4 per condition). Additional plasma samples diluted with NS or
      VOL (0% or 30%) were exposed to 0 MUmol/L or 100 MUmol/L CORM-2 and 0 U/mL or 100
      U/mL tissue-type plasminogen activator to assess fibrinolytic vulnerability (n =
      8 per condition). Thrombelastographic data were collected until either clot
      strength stabilized or clot lysis occurred, as appropriate. RESULTS: CORM-2
      exposure maintained normal to supranormal velocity of clot formation and strength
      in plasma diluted up to 40% with NS. In contrast, although CORM-2 exposure
      improved coagulation kinetics, dilution with VOL markedly degraded thrombus
      formation kinetics. Similarly, fibrinolytic vulnerability to tissue-type
      plasminogen activator was markedly improved by CORM-2 exposure in samples diluted
      with NS, whereas VOL-diluted thrombi were still abnormally weak and easily lysed
      compared with undiluted samples despite CORM-2 exposure. CONCLUSIONS: CORM-2
      exposure attenuated the decrease in coagulation kinetics and enhancement of
      fibrinolytic vulnerability associated with hemodilution. Extensive preclinical
      investigation remains to be performed to determine the route of administration,
      safety, and efficacy of CORM-2 and other CORMs to treat trauma-associated
      bleeding.

PMID- 20693920
TI  - Triage and trauma workload in mass casualty: a computer model.
AB  - BACKGROUND: The aim of this study was to quantitatively analyze the impact of
      hospital triage on the workload of trauma teams in the Emergency Department
      during a mass casualty incident, using a computer model. METHODS: The inflow and
      triage of casualties into an Emergency Department with 5 trauma teams was modeled
      using the Monte Carlo method. Triage was represented as a binary classification
      task performed in one or two sequential steps. The input variables were triage
      accuracy (specificity and sensitivity) and casualty load, and the key output
      variable was the time to saturation (TTS) of the trauma teams, which was computed
      from the available and needed team minutes. RESULTS: The relationship between an
      increasing casualty load and the TTS describes a sigmoid-shaped curve. Improving
      triage accuracy extends the TTS and shifts the curve to the right. Switching to
      sequential competent triage (80% accuracy) results in TTS that is similar to
      perfect single-step triage (100% accuracy) but at the cost of investing less team
      time in urgent casualties. The optimal ratio of trauma teams to urgent casualties
      in sequential mode is 1:8, indicating that the treatment of urgent casualties
      must be delegated to reinforcement staff. CONCLUSIONS: This study introduces
      innovative tools for quantitative analysis of hospital triage in mass casualty
      incidents and shows how triage accuracy and mode affect the ability of trauma
      teams to cope with heavy casualty loads. These tools can be used to optimize the
      hospital response to future threats.

PMID- 20693922
TI  - Intraabdominal vascular injury: are we getting any better?
AB  - BACKGROUND: Intraabdominal vascular injury (IAVI) as a result of penetrating and
      blunt trauma carries a high mortality rate. This study was performed to compare
      current mortality rates with a previously reported historic control. METHODS: The
      experience at our institution from 1970 to 1981 was previously reported with an
      overall mortality rate of 32% in 112 patients with penetrating IAVI. In a
      retrospective analysis, this historic cohort was compared with 248 patients with
      penetrating and blunt IAVI during a 138-month interval ending in June 2007.
      RESULTS: Overall mortality rate was 28.6%. The most commonly injured arteries
      were the iliac artery, aorta, and superior mesenteric artery. The most commonly
      injured veins were the inferior vena cava, iliac vein, and portal vein. Injury to
      the aorta, IVC, and portal vein had the highest mortality rates of 67.8%, 42.1%,
      and 66.6%, respectively. One hundred forty-four patients with one vessel injured
      had a mortality rate of 18.7%, whereas those with more than one vessel injured
      had a mortality rate of 48.7% (p < 0.001). A total of 46% of 117 patients in
      shock died compared with 9.6% of 104 patients not in shock (p < 0.001). Patients
      with a base deficit of less than -15 had a mortality rate of 72%, whereas those
      with a base deficit of 0 to -15 (p < 0.001) had a mortality rate of 18.9%. There
      was no difference in the overall mortality rate for penetrating trauma compared
      with the previous study. CONCLUSIONS: Although over 20 years have passed, no
      significant changes have occurred in the mortality associated with IAVI. Patients
      presenting in shock with IAVI continue to have a high mortality rate.

PMID- 20693923
TI  - Early administration of L-arginine in experimental acute spinal cord injury
      impairs long-term motor function recovery.
AB  - BACKGROUND: Recently, we reported that L-arginine, a nitric oxide precursor,
      reverses altered drug disposition induced by acute spinal cord injury (SCI) by
      increasing hepatic blood flow, without affecting mean arterial pressure and heart
      rate, whereas others have shown that it produces neuroprotection in several
      models of acute neurologic damage. Its use as a therapeutic agent for
      microcirculatory alterations associated with spinal shock seems promising.
      Therefore, here we have tested its influence on long-term morphofunctional
      neurologic outcome. METHODS: Intravenous L-arginine (300 mg/kg per dose) was
      administered to adult rats after SCI of moderate intensity according to the
      following schemes (n=6): (1) single dose at 1 hour, (2) single dose at 24 hour,
      and (3) repeated doses first at 24 hour and then daily for 7 days. Control
      injured rats received the vehicle (saline solution). RESULTS: Contrary to our
      expectations, locomotor function, assessed using the Basso-Beattie-Bresnahan
      scale for 8 weeks, was significantly worse in the L-arginine treated groups
      compared with the control group. Areas of both spared white matter and myelin
      stain at the epicenter seemed reduced in rats that received L-arginine as a
      single dose at 1 hour after injury but were not significantly different from the
      control group. CONCLUSIONS: L-arginine as used here interfered with the
      functional outcome of rats subjected to SCI, suggesting that L-arginine or its
      metabolic products may be neurotoxic. Because of its potential utility for acute
      SCI suggested in the past, strategies should be designed to block its apparent
      neurotoxicity.

PMID- 20693924
TI  - Volar locking plates versus K-wire fixation of dorsally displaced distal radius
      fractures--a functional outcome study.
AB  - BACKGROUND: Fractures of the distal radius are common. As the population of the
      western world ages, their incidence is set to increase further. There are various
      methods of treating these fractures, but optimal management remains
      controversial. In the United Kingdom, the most common surgical treatment of
      closed distal radius fractures is by Kirschner-wires (K-wires) or volar locking
      plate. In this study, we compared long-term functional outcomes of volar locking
      plates with those of K-wires. METHODS: A retrospective comparative study of 71
      patients with dorsally displaced distal radius fractures treated
      contemporaneously in two independent hospitals was performed. One group was
      treated with a volar locking plate (n = 36) and the other group with manipulation
      and K-wire fixation (n = 35). There was no difference between the two groups in
      terms of demographics or grade of fracture. Outcome was measured 15 months to 27
      months post surgery using the Disabilities of the Arm, Shoulder and Hand score
      and the Patient-Rated Wrist Evaluation score. RESULTS: We found no statistical
      difference between the two groups in the Patient-Rated Wrist Evaluation score or
      Disabilities of the Arm, Shoulder and Hand score at 1 year to 2 years
      postsurgery. CONCLUSION: We have been unable to demonstrate a clinically relevant
      advantage of using volar locking plates over K-wires at 1 year to 2 years
      postoperatively.

PMID- 20693925
TI  - Directness of transport of major trauma patients to a level I trauma center: a
      propensity-adjusted survival analysis of the impact on short-term mortality.
AB  - BACKGROUND: Whether severely injured patients should be transported directly to
      tertiary trauma centers, bypassing closer nontertiary facilities, or be
      transported first to nearby, less-specialized facilities for immediate care and
      stabilization has been studied with mixed findings. Differences in study locale,
      case mix, and variation in the structure and level of maturation of the trauma
      system may explain some of the discrepancy in findings. In addition, risk
      adjustment strategies used in these studies did not take into account prehospital
      baseline characteristics as well as time since injury. METHODS: This was a
      retrospective cohort study of 1,998 patients treated at a Level I trauma center
      between January 1, 2006, and December 31, 2007. Propensity-adjusted survival
      analyses were used to compare short-term mortality outcomes in transferred versus
      directly transported major trauma patients. RESULTS: A total of 1,398 patients
      were transported directly to the Level I trauma center and 600 patients were
      transferred from lower level facilities. After adjusting for the propensity to be
      transported directly, age, injury severity score, severe head injury, emergency
      medical service or emergency department intubation, comorbid conditions, and time
      to definitive Level I trauma care, the 2-week mortality risk in transferred
      patients was almost three-fold that of patients transported directly to a Level I
      trauma center (hazard ratio, 2.7; 95% confidence interval, 1.31-5.6). CONCLUSION:
      Transferred patients in a predominantly rural region are at an increased risk of
      short-term mortality. This suggests that severely injured patients should be
      transported directly to tertiary trauma centers. For patients requiring immediate
      stabilization at nontertiary facilities, this should be performed promptly
      without unnecessary delays.

PMID- 20693926
TI  - The effects of injury magnitude on the kinetics of the acute phase response.
AB  - BACKGROUND: The acute-phase response (APR) is critical to the body's ability to
      successfully respond to injury. A murine model of closed unilateral femur
      fractures and bilateral femur fracture were used to study the effect of injury
      magnitude on this response. METHODS: Standardized unilateral femur fracture and
      bilateral femur fracture in mice were performed. The femur fracture sites,
      livers, and serum were harvested over time after injury. Changes in mRNA
      expression of cytokines, hepatic acute-phase proteins, and serum cytokines
      overtime were measured. RESULTS: There was a rapid and short-lived hepatic APR to
      fracture injuries. The overall pattern in both models was similar. Both acute
      phase proteins' mRNA (fibrinogen-gamma and serum amyloid A-3) showed increased
      mRNA expression over baseline within the first 48 hours and their levels
      positively correlated with the extent of injury. However, increased severity of
      injury resulted in a delayed induction of the APR. A similar effect on the gene
      expression of cytokines (interleukin [IL]-1beta, IL-6, and tumor necrosis factor
      alpha) at the fracture site was seen. Serum IL-6 levels increased with increased
      injury and showed no delay between injury models. CONCLUSIONS: Greater severity
      of injury resulted in a delayed induction of the liver's APR and a diminished
      expression of cytokines at the fracture site. Serum IL-6 levels were calibrated
      to the extent of the injury, and changes may represent mechanisms by which the
      local organ responses to injury are regulated by the injury magnitude.

PMID- 20693927
TI  - Treatment of complex elbow injuries with a postoperative custom-made progressive
      stretching static elbow splint.
AB  - BACKGROUND: Complex elbow injuries consist of fractures of one or several of the
      bony stabilizers of the elbow, including the radial head, proximal ulna, coronoid
      process, collateral ligaments, and capsular complex. These injuries, if not
      properly treated, were reported to have a poor prognosis with recurrent
      instability, stiffness, posttraumatic arthrosis, and pain. This study was
      conducted to review clinical outcomes after fracture stabilization and ligament
      repair with a postoperative custom-made progressive stretching (CMPS) elbow
      splint in the treatment of complex elbow injuries. METHODS: From December 2001 to
      October 2006, 14 patients with complex elbow fractures or instability underwent
      surgery in Far Eastern Memorial Hospital by Chang Chih-Hung, using suture
      anchors. All patients used our CMPS static elbow splint postoperatively. No
      hinged elbow external skeletal fixator was necessary. The results were reviewed
      retrospectively. RESULTS: The patients were followed up for an average of 14
      months. The mean (standard deviation) flexion-extension range of motion (ROM) was
      116-degree angle (23-degree angle). The mean Mayo Elbow Performance Score was 92
      points; the results were excellent in 10 patients, good in three patients, and
      fair in one patient. CONCLUSION: The dilemma in managing complex elbow injuries
      is that extended immobilization leads to stiffness, but without proper
      reconstruction of the stabilizer, joint instability recurs. Our surgical protocol
      included removal of all loose bodies within the joint, stable fixation of
      fracture fragments if possible, and use of suture anchors to repair medial or
      lateral ulnar collateral ligaments. CMPS static elbow splints provided both
      postoperative protection and ROM movement. In our experience, if the stabilizers
      were reconstructed, hinged elbow external skeletal fixator is usually not
      necessary, and progressive stretching by CMPS splint can result in good ROM.

PMID- 20693928
TI  - Facial fractures in the elderly: a retrospective study in a hospital in Belo
      Horizonte, Brazil.
AB  - BACKGROUND: An increasing incidence of maxillofacial trauma in the elderly has
      been noted, as a consequence of increased longevity, resulting in a higher
      percentage of elderly people in the population. METHODS: A retrospective study
      was undertaken to assess facial fractures in elderly presenting during the period
      2000 to 2002 in Belo Horizonte, Brazil. The data collected included age, gender,
      etiology, date of trauma, maxillofacial trauma, anatomic site of fracture, and
      treatment. The statistical analysis involved evaluation of measures of central
      tendency and variability and calculation of proportions. RESULTS: It encountered
      165 facial fractures in 122 elderly aged 60 years or older. The majority of
      fractures were sustained by elderly in the age group 60 years to 69 years. Falls
      was the major cause of trauma followed by car accidents. The mandible was found
      to be the most common fractured bone in the facial skeleton, followed by the
      zygomatic complex. A conservative approach was accomplished in the most of cases.
      CONCLUSION: Gender was associated with the presence or absence of fractures and
      with the etiology. There was no association between age and fractures. No
      association was found between etiology and age for women and men. The proportion
      of fractures of the zygomatic arch, mandible body, and parasymphysis treated
      surgically were statistically higher than the same proportion among the cases of
      other fractures. The fractures of the nose were more often treated conservatively
      than other fractures.

PMID- 20693929
TI  - Back to basics: Identifying and managing acute spinal cord injury.

PMID- 20693930
TI  - Who do you want to be when you grow up?

PMID- 20693931
TI  - Computed tomography may demonstrate pseudosubarachnoid hemorrhage in diffuse
      cerebral edema after cardiorespiratory arrest.
AB  - OBJECTIVE: To report the cases of two children who died from diffuse cerebral
      edema after cardiorespiratory arrest and who had radiologic findings of
      subarachnoid hemorrhage on computed tomography, the presence of which was
      excluded on subsequent postmortem examination. DATA SOURCES: Case notes, clinical
      records, and postmortem reports of two children who became brain stem dead after
      cardiorespiratory arrest. CONCLUSIONS: Radiologic mimics of subarachnoid
      hemorrhage have been reported in the adult literature and are termed
      pseudosubarachnoid hemorrhage. A diagnosis of pseudosubarachnoid hemorrhage,
      rather than true subarachnoid hemorrhage, should be considered in the context of
      diffuse cerebral edema after cardiorespiratory arrest. Interpretation of the
      radiologic finding of subarachnoid hemorrhage in a child after a prolonged
      cardiac arrest should be cautious to avoid unnecessary and deleterious management
      and investigation for aneurysms.

PMID- 20693932
TI  - Ipsilateral lobar emphysema in an infant with a repaired congenital diaphragmatic
      hernia.
AB  - OBJECTIVE: To report a case of lobar emphysema in an infant who had a congenital
      diaphragmatic hernia that was surgically repaired at birth. DESIGN: Case report.
      SETTING: Pediatric critical care unit in a tertiary care hospital. PATIENT: A 9
      month-old infant who had massive hyperinflation of the right lung and respiratory
      failure. INTERVENTIONS: Confirmation of lobar hyperinflation of the right lung
      with ventilation and perfusion defects and surgical treatment with lobectomy.
      MEASUREMENTS AND MAIN RESULTS: Successful treatment of respiratory failure.
      CONCLUSION: Lobar emphysema can be a rare development in patients who had a
      congenital diaphragmatic hernia at birth. This can result in respiratory failure
      and needs surgical intervention.

PMID- 20693933
TI  - Inhaled nitric oxide improves oxygen saturation in children with pulmonary
      arteriovenous malformations after the Fontan procedure.
AB  - OBJECTIVE: To report the utility of inhaled nitric oxide to ameliorate excessive
      hypoxemia in children with pulmonary arteriovenous malformations after the Fontan
      procedure. DESIGN: Case series. SETTING: A tertiary pediatric cardiac intensive
      care unit in a freestanding children's hospital. PATIENTS: Three children with
      complex congenital heart disease and pulmonary arteriovenous malformations who
      underwent the Fontan procedure. INTERVENTIONS: The 3 patients all exhibited
      moderate-to-severe hypoxemia in the immediate postoperative period. The hypoxemia
      persisted despite mechanical ventilation and oxygen at an Fio2 of 1.0. Inhaled
      nitric oxide was initiated with immediate and dramatic improvements in oxygen
      saturation in all patients. All patients were eventually weaned off inhaled
      nitric oxide. CONCLUSIONS: The use of inhaled nitric oxide in patients with
      pulmonary arteriovenous malformations after having the Fontan procedure improves
      hypoxemia and may potentially reduce postoperative morbidity, unnecessary
      testing, and duration of hospital stay.

PMID- 20693934
TI  - Survival after extreme left atrial hypertension and pulmonary hemorrhage in an
      infant supported with extracorporeal membrane oxygenation for refractory atrial
      flutter.
AB  - OBJECTIVE: We report here the survival of an infant who developed extreme left
      atrial hypertension and severe pulmonary hemorrhage while supported with
      extracorporeal membrane oxygenation for refractory atrial flutter. The patient
      recovered after decompression of the left heart and catheter ablation of the
      atrioventricular node. SETTING: Lucile Packard Children's Hospital (Stanford,
      CA). DATA SOURCE: Chart review. CONCLUSIONS: Recovery of lung function is
      possible despite systemic-level left atrial pressure resulting in pulmonary
      hemorrhage and complete solidification of lung parenchyma on gross inspection.
      Resolution of pulmonary hemorrhage despite anticoagulation while on
      extracorporeal membrane oxygenation can occur after relief of left atrial
      hypertension.

PMID- 20693935
TI  - Spectrum bias and loss of statistical power in discordant couple studies of
      sexually transmitted infections.
AB  - BACKGROUND: Discordant couple studies are frequently used to evaluate preventive
      interventions for sexually transmitted infections (STI). This study design may be
      vulnerable to spectrum bias when transmission risk is heterogeneous. METHODS: We
      used Markov models to assess the effect of heterogeneous transmission risk on the
      ability to detect effective interventions using a discordant couple study design.
      We also evaluated the implications that such bias may have for statistical power.
      Models incorporated potential health states in a population of initially
      infection-discordant couples, according to infection status with a hypothetical
      STI and participation in a hypothetical clinical research study. We evaluated the
      effect of length of discordant relationship at time of study enrollment, the
      shape of distribution describing transmission risk among couples, and the effect
      of sex-specific differential transmission probabilities, on model outcomes.
      RESULTS: The results demonstrate that discordant couple studies are prone to
      spectrum bias, the degree of which is affected by the shape of the underlying
      transmission probability density function. CONCLUSIONS: Such bias could lead to
      unexpected study findings, including gender-specific vaccine effects, and loss of
      statistical power, making this an important and underrecognized consideration in
      the design and interpretation of discordant couple studies.

PMID- 20693936
TI  - Improving partner services by embedding disease intervention specialists in HIV
      clinics.
AB  - BACKGROUND/OBJECTIVES: Notifying partners of HIV-infected persons and referring
      them for testing and treatment is an effective method of disease control and
      identification of undiagnosed STD and/or HIV. To improve partner elicitation
      interviews, disease intervention specialists (DIS) were placed in 3 HIV clinics
      during 2008 and 2009. METHODS: We reviewed the Arizona state STD surveillance
      database for 2007 to identify the providers (outside of the public STD clinics)
      reporting the highest number of syphilis cases. DIS were placed in the clinics
      for half a day per week (2 clinics) or on an on-call basis (1 clinic) to deliver
      penicillin and interview patients. We calculated changes in the number of
      patients interviewed, days elapsed from specimen collection to treatment (time to
      treatment), days elapsed from specimen collection to initial DIS contact (time to
      interview), and number of reported and locatable partners from these 3 clinics
      before and after the clinic placement of DIS. RESULTS: Before the placement of
      clinic-based DIS, 219 syphilis cases were diagnosed at the 3 clinics (January
      2006 through January 2008). After DIS placement, 115 syphilis cases were
      diagnosed (February 2008 through September 2009) for a total of 334 cases in this
      analysis. A greater percent of patients completed a partner elicitation interview
      during the period of DIS placement (94% after vs. 81% before, P = 0.001). There
      were increases in the average number of locatable partners (1.1 after vs. 0.6
      before, P = 0.004) and an increase in the average number of partners exposed and
      brought to treatment (CDC Disposition A) or infected and brought to treatment
      (CDC Disposition C) (0.6 after vs. 0.3 before, P = 0.02), and the time to
      interview decreased (18 days before vs. 9 days after, P = 0.02).
      CONCLUSIONS/IMPLICATIONS: Placing DIS within community HIV clinics improved
      partner services. STD and/or HIV programs should consider this method to improve
      partner notification.

PMID- 20693937
TI  - Evaluation of a novel serology algorithm to detect herpes simplex virus 1 or 2
      antibodies.
AB  - BACKGROUND: Herpes simplex virus (HSV)-type specific serology (TSS) testing has
      been commercially available for nearly a decade. Guidelines on appropriate use of
      such testing exist, including Canadian-based recommendations. Despite this, most
      Canadian laboratories do not offer HSV-type specific serology and many provide
      only nontype-specific HSV serology tests. METHODS: At the Alberta Provincial
      Laboratory, HSV TSS is performed using the following algorithm (termed the
      Alberta algorithm). Eligible specimens are first tested with a nontype-specific
      kit (Behring Enzygnost IgG). If positive, sera are then tested using the Focus
      HerpeSelect-2 assay to establish HSV-2 infection. If the HerpeSelect-2 result is
      negative, the result is reported as anti-HSV-1 positive. In this study we sought
      a validation of the Alberta algorithm by testing 344 serum samples with the
      Behring Enzygnost IgG assay, the type specific Focus HerpeSelect 1 and 2 assays,
      and by Western blot (WB). RESULTS: Taking the WB as a gold standard, the Behring
      Enzygnost IgG assay showed a sensitivity of 94% and a specificity of 100%,
      whereas the Alberta algorithm had a sensitivity of 92% and a specificity of 97%
      for the detection of HSV-2 antibodies, and a sensitivity of 94% and a specificity
      of 100% for the detection of HSV-1 antibodies in HSV-2 negative sera. Focus
      HerpeSelect 1 and HerpeSelect 2 sensitivities against WB were 88% and 91%,
      whereas specificities were 95% and 97% for HSV-1 and HSV-2, respectively.
      CONCLUSIONS: The Alberta algorithm was at least equivalent to HerpeSelect 1 and 2
      in detecting anti-HSV antibodies. Although sensitivity and specificity were
      higher, the differences were not statistically significant.

PMID- 20693938
TI  - Potential for sexual transmission of HIV infection from male injecting-drug users
      who have sex with men in Tehran, Iran.
AB  - BACKGROUND: Iran faced an HIV epidemic among injecting-drug users (IDUs) and has
      responded to this threat. Meanwhile, there is growing concern over the
      possibility of bridging HIV infection from IDUs to other populations, including
      men who have sex with men (MSM). METHODS: Cross-sectional biobehavioral surveys
      were conducted among 370 injecting-drug users recruited from drug treatment
      centers, a drop-in center, as well as streets in drug-populated areas in Tehran,
      Iran, between 2003 and 2004. RESULTS: Data from these surveys showed that about
      12% of male, sexually experienced IDUs have had same-gender sex, and HIV
      prevalence is high (19%), but condom use during the last sexual encounter was low
      (20%). A multivariate analysis showed that IDUs who had sex with men (MSM IDUs),
      compared to other sexually experienced IDUs, are younger (AOR, 0.89; 95% CI, 0.81
      0.98), more likely to have used a shared needle/syringe for drug injection (AOR,
      4.29; 95% CI, 1.82-10.12), and have had more than 5 sexual partners in their
      lifetime (AOR, 2.71; 95% CI, 1.14-6.44). CONCLUSIONS: These results show that MSM
      IDUs exhibit more drug-related and sexual risk behaviors that may serve as a
      bridge for sexual transmission of HIV to other populations, including the broader
      MSM community, in Tehran. This report intends to encourage health authorities in
      Iran to take serious action to prevent sexual transmission of HIV from MSM IDUs
      to their sexual networks.

PMID- 20693940
TI  - Unknown case: low back pain in a patient with cafe au lait spots. Diagnosis: NF
      1.

PMID- 20693942
TI  - Radiographic evaluation of the technique for C1 lateral mass and C2 pedicle screw
      fixation in three hundred nineteen cases.
AB  - STUDY DESIGN: Retrospective radiographic study of the technique for C1 lateral
      mass screw (C1LMS) and C2 pedicle screw (C2PS) fixation. OBJECTIVE: To evaluate
      (1) the accuracy of the C1LMS and C2PS placement; (2) the fusion rate between C1
      and C2; (3) the risk for vertebral artery (VA) injury. SUMMARY OF BACKGROUND
      DATA: C1LMS and C2PS fixation is widely used when treating atlantoaxial
      instability. Several authors have reported their experience focusing on the
      technical outcomes, with many reporting fusion rates near 100%. However, most of
      them are relatively small series, and many have applied only plain postoperative
      radiographs instead of computed tomography (CT). Thus, we feel that the accuracy
      of C1LMS and C2PS placement has not been fully analyzed, as well as the anatomic
      relationship between the VA and the screws. METHODS: Between December 2000 and
      September 2008, the fusion status and accuracy of the screws were evaluated on
      the postoperative reconstructive CT of 319 patients with atlantoaxial
      instability. Cases with malpositioned screws underwent CT angiography or magnetic
      resonance angiography after surgery, to evaluate potential VA injury. RESULTS:
      C1LMS of 95.5% and C2PS of 92.8% were found to be in a "good" position. After
      2007, six cases had malpositioned screws, which were all in the "out" or "down"
      area of the C2 pedicle. Five cases underwent CT angiography and 1 had magnetic
      resonance angiography to evaluate potential VA injury. No occlusion, associated
      aneurysm or fistula of the VA was found. All cases (100%) achieved solid fusion
      between C1 and C2. CONCLUSION: C1LMS of 95.5% and C2PS of 92.8% were confirmed to
      be in good position. None of the screws including the malpositioned caused VA
      injury, clinically or radiographically. The technique for C1LMS and C2PS fixation
      appears to be safe and effective.

PMID- 20693943
TI  - How to prevent and manage Diabetic Kidney Disease in the Republic of Macedonia.
AB  - The Macedonian Society of Nephrology, Dialysis, Transplantation and Artificial
      Organs, the Macedonian Society of Nephrology and the Macedonian Society of
      Endocrinology and Metabolic Diseases and the general physicians held a one-day
      meeting on 11 March 2010 at the Macedonian Academy of Sciences and Arts devoted
      to the prevention and treatment of diabetic kidney disease. In the Republic of
      Macedonia there are about 100,000 patients with diabetes mellitus type 1 and 2;
      85-95 % have diabetes mellitus type 2. On insulin therapy there are around 28,000
      30,000 patients. In our papers: Chronic Kidney Disease: a Hidden Epidemic (2) and
      Public Health Aspects of Renal Disease in the Republic of Macedonia 1983-2007 (3)
      we have shown a continuous increase of end stage renal disease and renal
      replacement therapy (RRT) in the Republic of Macedonia. In 2002, we had 1,056
      patients on RRT compared to 1,216 in 2005. In some dialysis centres 20% of the
      patients on haemodialysis are diabetics. Our message was that there is an urgent
      need for a screening programme for the detection of Chronic Kidney Disease (CKD)
      and we will suggest developing a strategy to check each patient in the Republic
      of Macedonia with diabetes mellitus, to detect early diabetic kidney disease by
      screening for albuminuria as well as for a reduced glomerular filtration rate.
      Health authorities, nephrologists and general physiccians should collaborate on
      the detection of CKD. In our country we should work harder on the prevention of
      diabetic kidney diseases, to stop or postpone the development of CKD and chronic
      renal failure with modern therapy and the need for RRT.

PMID- 20693944
TI  - The new Oxford Clinico-Pathological Classification of IgA nephropathy.
AB  - The new Oxford Classification of the Pathology of IgA nephropathy originated from
      an international collaborative effort of the Working Group of the International
      IgA Nephropathy Network and Renal Pathology Society. It provides a new common
      language to categorizing glomerular and tubulo-interstitial lesions in IgA
      nephropathy having a proved effect on progression. Although retrospective in
      design and requiring future prospective validation, the Oxford collaboration
      defined and scored four pathologic parameters having an influence on outcome
      (independently of clinical information at renal biopsy or during follow-up);
      including mesangial (M) and endocapillary (E) proliferation (hypercellularity),
      glomerulosclerosis (S) and tubular atrophy and interstitial fibrosis (T). The
      scheme will likely become known as the OXFORD-MEST scoring system.

PMID- 20693945
TI  - Benefits of screening for Chronic Kidney Disease.
AB  - The number of patients on renal replacement therapy has doubled every decade
      since 1980, and prevalence of chronic kidney disease (CKD) in the early stages is
      also markedly increased. In addition, CKD is a significant risk factor for
      cardiovascular morbidity and mortality. The only effective approach to this
      problem is prevention and early detection of CKD. In recent years, screening
      studies have been carried out in several countries. The findings have defined the
      scope of the problem and indicated which population groups are at risk of
      developing CKD. The most numerous are patients with hypertension and diabetes.
      Also, these studies have indicated that screening should include measurement of
      serum creatinine for eGFR as well as urine albumin. Early detection of CKD allows
      proper management that could slow down CKD progression, prevent cardiovascular
      and other comorbidities and enable timely initiation of dialysis. Screening for
      CKD could be best managed by partnership between primary care physicians and
      nephrologists. It is necessary to educate primary care physicians about CKD, its
      risk factors and associated co-morbidities. Although multiple benefits of
      screening for CKD are doubtless, the results obtained by screening should be
      interpreted with caution, bearing in mind that screening detects only markers of
      kidney disease but not the disease itself.

PMID- 20693946
TI  - Diabetics on dialysis in the Republic of Macedonia: A nationwide epidemiological
      study.
AB  - BACKGROUND: Incidence increase of diabetes mellitus (DM) has taken epidemic
      proportions in the world. Diabetic nephropathy (DN) is a most serious
      complication, taking a leading place as a factor in the progression of chronic
      kidney disease (CKD). Dialysis treatment of these patients is complex, expensive,
      and exerts an excessive burden on the health budgets of the affected countries.
      METHODS: We performed a nationwide precise observational study with the aim of
      analysing diabetics on dialysis in dialysis centres throughout the Republic of
      Macedonia (RM) in 2002 and in 2006; to compare the results from patients records;
      and to gather data on the epidemiology, clinical characteristics and
      complications of diabetes type 1 (DM1) and diabetes type 2 (DM2). RESULTS: The
      prevalence of HD patients in RM was 1114 vs 1074 in 2002 and 2006, respectively.
      Of these, 109 (9.78%) vs. 115 (10.71%) had DM in 2002 and 2006, respectively. The
      percentage of diabetics on dialysis between different centers varied between 3%
      to 21% vs. 2.4% to 22.07% in 2002 and 2006, respectively. The mean age of the
      patients was 58+/-10.29 vs. 56.5+/-10.71 in 2002 and 2006, respectively. Patients
      with DM1 were 19 (17.43%) vs. 15 (13.04%) and with DM2 were 90 (82.57%) vs. 100
      (86.96%) in 2002 and 2006, respectively. 28 (25.68%) vs. 31 (26.96%) patients
      were on oral anti-diabetic drugs and 62 (57.21%) vs. 69 (60%) patients were on
      insulin in 2002 and 2006, respectively. Mean age of DM1 patients was 47+/-11.6 y.
      vs. 45+/-7.32 y. respectively and of DM2 was 60.37+/-8.33 y. vs. 61.14+/-10.23
      y., in 2002 and 2006, respectively. Mean time of insulin treatment was 9.5+/-6.63
      y. vs. 10.85+/-9.29 y. in 2002 and 2006. Mean Body Mass Index (BMI) was 26.4 vs.
      23.49+/-4.74 kg/m2 in DM1 and 25.5 vs. 24.77+/-3.70 kg/m2 in DM2 patients in 2002
      and 2006, respectively. Thrombosis of first arteriovenous fistulae (AVF) occurred
      in 41% vs. 25.22% in 2002 and 2006, respecttitvely. Hepatitis C virus (HCV)
      infection was confirmed in 57% vs. 44% of DM patients in 2002 and 2006,
      respectively. Most common co-morbidity in patients was hypertension, 91% vs.
      80.87% in 2002 and 2006, respectively. CONCLUSION: The number of diabetics on
      dialysis in the Republic of Macedonia did not increase in the period from 2002 to
      2006. In DM2 diabetics on dialysis the frequency of complications is higher and
      time on dialysis is shorter than in DM1 patients. Early detection of diabetic
      nephropathy by primary care physicians as well as collaborative treatment by
      diabetologists, nephrologists, cardiologists and ophthalmologists before and
      during dialysis are important for improvement of treatment and survival of
      diabetic patients on dialysis.

PMID- 20693947
TI  - Dose-dependent therapeutic effects of 2-Methoxyestradiol on Monocrotaline-Induced
      pulmonary hypertension and vascular remodelling.
AB  - 2-Methoxyestradiol (2ME) is a major non-oestrogenic metabolite of oestradiol. Our
      previous studies, performed in several models of cardiac and/or vascular injury,
      suggest that 2ME strongly inhibits both pressure-dependent and pressure
      independent cardiac and vascular remodelling. Furthermore, recently we have shown
      that in male rats 2ME attenuates the development and retards the progression of
      monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH); and in female
      rats 2ME eliminates the exacerbation of PAH and increased mortality due to
      ovariectomy. In the present study we compared the therapeutic effects of three
      different doses of 2ME (3, 10 and 30 microg/kg/hour; 2ME-3, 2ME-10 and 2ME-30,
      respectively) in male rats with MCT-induced PAH. The animals were also monitored
      for plasma 2ME levels and potential oestrogenic effects. Treatments were
      initiated 12 days after administration of MCT (60 mg/kg, i.p.). Twenty-eight days
      post MCT, right ventricular peak systolic pressure (RVPSP) was measured and
      morphometric analysis was conducted. All three doses of 2ME produced beneficial
      therapeutic effects in pulmonary hypertensive animals, i.e. reduced pulmonary
      artery pressure and right ventricular hypertrophy, attenuated pulmonary vascular
      remodelling and inflammatory response, and had favourable effects on survival.
      Notably, none of the three doses had any effect on plasma testosterone levels or
      on seminal vesicle or testicle weight. Dose-dependent increases in 2ME plasma
      levels were observed only with 2ME-3 and 2ME-10; 2ME-30 produced 2ME plasma
      levels similar to those seen with 2ME10. Nonetheless, 2ME-30 was significantly
      more efficacious than 2ME-3 or 2ME-10 and eliminated the high mortality (34%)
      induced by MCT. In summary, the present study indicates that 2ME, used in doses
      that produce plasma levels similar to those seen in the last trimester of
      pregnancy (1000-3000 pg/ml), is effective and safe (i.e. has no oestrogenic
      effects) in experimental PAH. These data also suggest that 2ME disposition,
      rather than plasma concentration, determines the therapeutic effects of 2ME in
      PAH.

PMID- 20693948
TI  - Post-corrosive injuries of upper gastrointestinal tract.
AB  - Acute poisonings with corrosive substances may cause serious chemical injuries to
      upper gastrointestinal tract, the most common location being the esophagus and
      the stomach. If the patient survives the acute phase of the poisoning,
      regenerative response may result in esophageal and/or gastric stenosis and
      increased risk for esophageal cancer. Acute corrosive intoxications pose a major
      problem in clinical toxicology since the most commonly affected population are
      the young with psychic disorders, suicidal intent and alcohol addiction. In
      establishing the diagnosis of acute corrosive poisonings, the severity of the
      post-corrosive endoscopic changes of the esophagus, stomach and duodenum is of
      major importance. According to Holinder and Fridman classification, post
      corrosive endoscopic changes are classified in three degrees: First degree-
      superficial damage associated with hyperthermia, epithelial desquamation and
      mucous edema. Second degree--transmucous damage affecting all of the mucosal
      layers, followed by exudation, erosions and ulcerations. Third degree--transmural
      damage associated with ulcer's penetration in the deep layers of the tissue and
      neighboring organs. Severity of the lesions depends on the nature, quantity and
      concentration of the corrosive substance, the duration of exposure and current
      state of the exposed organs. Most often caustic injuries occur to the esophagus
      and stomach since the corrosive substance remains there for a longer period of
      time. Treatment of the acute corrosive intoxications include: neutralization of
      corrosive agents, antibiotics, corticosteroids, anti-secretory therapy,
      nutritional support, collagen synthesis inhibitors, esophageal dilation and stent
      placement, and surgery. The most common complications that may appear are:
      perforation, gastrointestinal bleeding, sepsis, esophageal strictures and
      stenosis, stenosis of gastric antrum and pylorus, cancer of the esophagus and the
      stomach. Today, owing to the substantially enhanced diagnostic and therapeutic
      approach, the mortality percentage has been reduced from 20% to 1-5%. Women more
      often than men are intoxicated with corrosive substances; suicidal poisonings
      prevail; the most abused agents are hydrochloric acid (HCl) and sodium hydroxide;
      intoxications are more common in children (80% out of the total number of
      intoxications). In spite of the preventive measures for restriction of the trade
      with corrosive substances, standardization of their concentration and protective
      safety bottle caps, still the number of corrosive intoxications, the percentage
      of post-corrosive complications and the handicap are high. Acute corrosive
      intoxications are the leading cause of death in clinical toxicology.

PMID- 20693949
TI  - Dermatophytes in Republic of Macedonia.
AB  - A total of 1742 clinically suspected samples was examined for the incidence and
      distribution of dermatophytes in the Republic of Macedonia from June 2007 to Jan.
      2009. 600 dermatophytes were isolated and identified. In the studied period 9
      different dermatophyte species were isolated, namely Trichophyton rubrum
      (48.83%), Microsporum canis (20%), Trichophyton mentagrophytes var. interdigitale
      (16.83%), Epidermophyton floccosum (4.17%), Trichophyton verrucosum (3.83%),
      Trichophyton mentagrophytes var. mentagrophytes (3%), Trichophyton violaceum
      (1.67%), Microsporum ferrugineum (1%) and Microsporum gypseum (0.67%). The
      anthropophilic dermatophytic species are predominant. Tinea unguium
      (onychomycosis) (37.50%) is the most frequently diagnosed dermatophytosis
      followed by tinea pedis (19.17%), tinea corporis (15.33) and tinea capitis
      (15.17%). Furthermore there is an increased number of Microsporum canis isolates
      in tinea capitis patients. Microsporum canis infection of the scalp remains a
      serious epidemiological problem in R. Macedonia.

PMID- 20693950
TI  - Are there any clinical and EEG features associated with the occurrence of
      executive dysfunctions in patients with JME?
AB  - The aim of the study was to determine the possible relationship between different
      clinical and EEG features and executive functions in patients with juvenile
      myoclonic epilepsy (JME), i.e. to determine if sex, age, duration, absences,
      clinical asymmetric seizures, asymmetry or focality in epileptiform activity in
      EEG, EEG slow activity and familiar occurrences are associated with frontal
      dysfunction in JME patients. 28 patients (17 females, 11 males), mean age--22 y.
      were enrolled in the study. Executive functions were evaluated with the Wisconsin
      Card Sorting Test (WCST). Crosstabulation of certain characteristics have been
      used. The mean age at the beginning of epilepsy for the whole group was 13.5 y.
      and duration 8.5 y. All patients had myoclonic jerks, 28.6% of patients described
      unilateral predominance. Absences were registered in 42.9% patients. Bilateral
      spike or polyspikes/wave complexes were registered in 89.2% of patients,
      asymmetry of generalized discharges or focality in at least one EEG in 53.6% of
      patients, with anterior slow activity in 25% of them. Familiar occurrence was
      found in 42.9%. Of 28 patients, 14 had normal findings on WCST, while the other
      half of the patients did very poorly, achieving only 1-3 categories. Statistical
      analysis showed that only the female sex had p-value of 0.05, while other
      clinical and EEG features were not significantly associated with the occurrence
      of frontal impairment. Aside from female sex, no other clinical or EEG parameters
      were associated with the occurrence of executive dysfunction. But considering the
      relatively small sample size, our study may have been underpowered to detect
      subtle association and in our opinion, the current results must be replicated
      with a larger group of subjects to confirm the findings.

PMID- 20693951
TI  - Measuring nasal volumes with acoustic rhinometry.
AB  - OBJECTIVES: Acoustic rhinometry is used to objectively measure the minimal cross
      sectional area and volumes of nasal cavities. However, no data for healthy
      subjects has been reported in Macedonia. Therefore, we wanted to establish the
      normal range among healthy adults and to evaluate the changes after nasal
      decongestion. METHODS: We included 50 males and 50 females in this study (mean
      age: 23.2 years; age range: 19 to 40 years). An acoustic rhinometer was used to
      evaluate the first minimal cross-sectional area (MCA1), the distance from the tip
      of the probe to the first minimal cross-sectional area (D1), the second minimal
      cross sectional area (MCA2), the distance from the tip of the probe to the second
      minimal cross sectional area (D2), the volume between the tip of the nosepiece
      and 3 cm into the nasal cavity (V03), the volume of the nasal cavity between 2 to
      5 cm from the tip of the nosepiece (V25), the volume of the nasal cavity between
      4 to 7 cm from the tip of the nosepiece (V47), and the volume between the tip of
      the nosepiece and 7 cm into the nasal cavity (V07). These measurements were taken
      before and after nasal decongestion. RESULTS: Data acquired from the male group
      before decongestion were as follows: MCA1 L: 0.71+/-0.07 (cm2); D1 L: 0.34+/-0.05
      (cm); MCA2 L: 0.46+/-0.13 (cm2); D2 L: 2.46+/-0.11 (cm); MCA1 R: 0.73+/-0.06
      (cm2); D1 R: 0.35+/-0.05 (cm); MCA2 R: 0.47+/-0.11 (cm2); D2 R: 2.41+/-0.18 (cm);
      V03 L 2.59+/-0.82 (cm3); V25 L; 4.83+/-1.93 (cm3); V47 L; 7.82+/-2.94 (cm3); V07
      L: 11.48+/-4.23 (cm3); V03 R 2.55+/-0.72 (cm3); V25 R; 4.71+/-1.76 (cm3); V47 R;
      7.60+/-2.30 (cm3); V07 R: 12.03+/-3.65 (cm3); data acquired from the female group
      before decongestion were: MCA1 L: 0.65+/-0.12 (cm2); D1 L: 0.35+/-0.05 (cm); MCA2
      L: 0.50+/-0.12 (cm2); D2 L: 2.36+/-0.15 (cm); MCA1 R: 0.65+/-0.11 (cm2); D1 R:
      0.35+/-0.04 (cm); MCA2 R: 0.49+/-0.13 (cm2); D2 R: 2.41+/-0.13 (cm); V03 L 2.64+/
      0.58 (cm3); V25 L; 5.11+/-1.17 (cm3); V47 L; 8.30+/-2.20 (cm3); V07 L: 12.38+/
      3.19 (cm3); V03 R 2.42+/-0.56 (cm3); V25 R; 4.43+/-1.34 (cm3); V47 R; 7.35+/-2.29
      (cm3); V07 R: 11.06+/-3.19 (cm3) The increase in MCA1 and MCA2 after nasal
      decongestion was significant (p<0.001), both in females and males. The increases
      in V03, V25, V47 and V07 after nasal decongestion were statistically significant
      both in the female and male groups as well (p<0.001). CONCLUSION: Acoustic
      rhinometry is a convenient method for assessing the geometry of the nasal cavity.
      The maximal effect of decongestion is found in the anterior and middle parts of
      the nasal cavity, at the level of the inferior and middle turbinates.

PMID- 20693952
TI  - A case report of aggressive adult neuroblastoma mimicking acute leukemia with
      fulminant course and fatal outcome.
AB  - A case of aggressive adult neuroblastoma mimicking acute leukemia with fulminant
      course and fatal outcome is described. Pancytopenia and circulating blasts cells
      at presentation suggested the diagnosis of acute leukemia in the previously
      healthy 38 years old Caucasian male patient, but flow-cytometry analysis of the
      bone marrow disclosed the correct diagnosis of neuroblastoma. The immunophenotype
      was CD45-/CD56+/CD9+ in around 50% of the mononuclear cells, indicating
      neuroectodermal origin of the malignant cells. Subsequently, the diagnosis was
      confirmed by immunohistochemical staining of a bone marrow biopsy. A review of
      the reported cases of neuroblastoma with leukemic features showed that several of
      them were misdiagnosed as having leukemia and that the diagnosis of neuroblastoma
      was made at autopsy examination, indicating that misdiagnosis may happen more
      often than is appreciated. It is in our opinion that the diagnosis of
      neuroblastoma should be considered in all cases of acute leukemia and
      pancytopenia, regardless of the age group of the patients.

PMID- 20693954
TI  - Changes in bone mineral density and bone turnover markers in obese women after
      short-term weight loss therapy during a 5-year follow-up.
AB  - INTRODUCTION: The protective effect of adipocity on bone metabolism has not been
      confirmed during long-term follow-up. It is not known whether the rate of bone
      turnover and changes in mineral metabolism in obese people result from endocrine
      properties of the adipose tissue or merely the mechanical load. OBJECTIVES: The
      aim of the study was to evaluate bone and calcium-phosphorus metabolism in obese
      women during a 5-year follow-up. PATIENTS AND METHODS: The study involved 47
      obese women who underwent a 3-month weight loss therapy. We evaluated changes in
      the serum levels of parathormone (PTH), calcidiol (25(OH)D3), collagen type I
      crosslinked C-telopeptide (CTx-I), osteocalcin, total calcium, inorganic
      phosphates, and in bone mineral density. The control group consisted of 17
      healthy women with proper body weight. RESULTS: We observed a similar decrease in
      bone mineral density (BMD) in the lumbar spine and femoral neck, and a comparable
      decrease in the serum levels of CTx-I and osteocalcin in both groups during the 5
      year follow-up. Changes in serum PTH levels were not statistically significant.
      In obese women, a nonsignificant increase in the serum level of 25(OH)D3 was
      observed as early as after a 3-month weight loss therapy and during follow-up. In
      controls, serum 25(OH)D3 levels tended to decrease. During follow-up, the number
      of obese patients with disturbances in vitamin D metabolism decreased from 78.7%
      to 53.2% (P = 0.01). Such disturbances were observed in 35.3% of the control
      group. In obese patients, there was a positive correlation between the change in
      body mass and BMD in the proximal femur (r = 0.279, P = 0.04). In controls, there
      was a positive correlation between the change in body mass and BMD in the lumbar
      spine (r = 0.477, P = 0.05). CONCLUSIONS: In obese women who underwent weight
      loss therapy, the levels of bone turnover markers decreased and abnormal vitamin
      D metabolism was still observed during the 5-year follow-up.

PMID- 20693955
TI  - Insulin sensitivity in chronic pancreatitis and features of insulin resistance
      syndrome.
AB  - INTRODUCTION: Chronic pancreatitis predisposes to diabetes. Loss of endocrine
      function by beta-cells in the Langerhans islets is considered to be the main
      causative factor, although several studies have also suggested insulin resistance
      as a possible additional mechanism. OBJECTIVES: The aim of the study was to
      estimate insulin sensitivity in chronic pancreatitis in view of the coexisting
      meta bolic syndrome components. PATIENTS AND METHODS: The study involved 30
      patients (mean age 50.83 +/-6.61 years; 23.33% women, 76.66% men) diagnosed with
      chronic pancreatitis (using imaging tests). Insulin sensitivity with regard to
      the coexistent obesity, dyslipidemia, and arterial hypertension was measured
      using the euglycemic clamp method. RESULTS: Diabetes was present in 22 patients,
      impaired glucose tolerance in 4, and no carbohydrate metabolism disturbances in
      4. Insulin resistance was present in 22 patients (73.33%), in whom a higher
      prevalence of diabetes (77.27% vs. 62.5%) and prediabetes (13.63% vs. 12.5%) was
      observed. The analysis of anthropometric para meters revealed that individuals
      with a high index of central obesity had a statistically significantly lower
      tissue glucose utilization (TGU) (3.23 vs. 4.89 mg/kg/min; P = 0.02), although
      there were no obese patients in the study group according to the body mass index.
      No statistically significant differences in TGU were observed in relation to
      lipid disorders (total cholesterol, low- and high-density lipoprotein
      cholesterol, triglycerides) and arterial hypertension. CONCLUSIONS: In patients
      with chronic pancreatitis, lack of correlation between insulin sensitivity and
      meta bolic syndrome components may indicate that insulin resistance is related to
      primary disease or that an additional mechanism underlying pancreatic diabetes
      operates.

PMID- 20693956
TI  - Usefulness of transbronchial needle aspiration for initial lung cancer staging.
AB  - INTRODUCTION: Besides radio logical methods (especially positron emission
      tomography combined with computed tomography), endoscopic techniques including
      transbronchial needle aspiration (TBNA) of mediastinal lymph nodes play an
      important role in lung cancer staging, thus having a significant effect on
      further patient management. OBJECTIVES: The aim of the study was to investigate
      the diagnostic value of blind TBNA in staging of lung cancer, using systematic
      mediastinal lymph node dissection (SLND) at thoracotomy as a confirmatory test.
      PATIENTS AND METHODS: Patients with lung cancer and enlarged mediastinal lymph
      nodes on computed tomography scans underwent TBNA. Non-small cell lung cancer
      (NSCLC) patients with negative TBNA or with single-level N2 disease underwent
      thoracotomy with appropriate pulmonary resection and with SLND. RESULTS: In 84
      lung cancer patients, 166 TBNA were performed. Metastatic lymph node involvement
      was identified in 57 patients (67.9%). There were 10 patients (11.9%) with small
      cell lung cancer. Of the 74 NSCLC patients, TBNA revealed meta stases in 48
      (64.9%). Twenty-four TBNA-negative patients (32.4%) and 4 patients (5.4%) with
      single-level N2 disease underwent pulmonary resection with SLND. In 8 of 28
      operated patients (28.6%), N2 meta static nodes were identified. The per-patient
      analysis showed the sensitivity of TBNA to be 81.5%, specificity - 100%, accuracy
      - 86.5%, and negative predictive value (NPV) - 66.7%. CONCLUSIONS: Our results
      suggest that TBNA may be a useful method for initial NSCLC staging in patients
      suspected of N2-3 disease. Positive TBNA in 1 station only should not be
      considered as a true single-level N2 disease, because of a relatively low NPV for
      TBNA.

PMID- 20693957
TI  - TGF-beta1 in bronchoalveolar lavage fluid in diffuse parenchymal lung diseases
      and high-resolution computed tomography score.
AB  - INTRODUCTION: In the pathogenesis of diffuse parenchymal lung diseases (DPLDs),
      growth factors, including transforming growth factor beta1 (TGF-beta1), are
      responsible for cell proliferation, apoptosis, chemotaxis, and angiogenesis, and
      also for the production and secretion of some components of the extracellular
      matrix. OBJECTIVES: The aim of the study was to evaluate correlations in DPLDs
      between TGF-beta1 levels in bronchoalveolar lavage (BAL) fluid and high
      resolution computed tomography (HRCT) score. PATIENTS AND METHODS: The study was
      performed in 31 DPLD patients in whom a selection of lung segments with high and
      low intensity of abnormalities was estimated by HRCT score. All patients
      underwent BAL with TGF-beta1 measured by an enzyme immunoassay in BAL fluid and
      video-assisted thoracic surgery lung biopsy from both selected segments. RESULTS:
      All 31 patients were diagnosed, and based on histopathology, they were classified
      into 2 groups: idiopathic interstitial pneumonia (usual interstitial pneumonia -
      12, nonspecific inter stitial pneumonia - 2, cryptogenic organizing pneumonia -
      2, and desquamative interstitial pneumonia - 1) and granulomatous disease
      (sarcoidosis - 7, extrinsic allergic alveolitis - 5, and histiocytosis X - 2).
      The final analysis was performed in 28 patients who showed nonhomogenous
      distribution on HRCT. TGF-beta1 levels in BAL fluid were significantly higher in
      the areas with high intensity of abnormalities assessed by HRCT score (P = 0.018,
      analysis of variance). These levels were not different between the groups, but a
      trend towards higher levels in idiopathic inter stitial pneumonia was observed.
      CONCLUSIONS: The results confirm that TGF-beta1 may be a good but not specific
      marker of fibrosis in DPLDs. A significant positive correlation between TGF-beta1
      levels in BAL fluid and the HRCT score was observed.

PMID- 20693958
TI  - Self-assessed health status in Poland: EQ-5D findings from the Polish valuation
      study.
AB  - INTRODUCTION: There are no population norms currently available in Poland for any
      generic health-related quality of life (HRQoL) questionnaire for adults.
      OBJECTIVES: The aim of the study was to evaluate the health status of a
      representative sample of the general Polish population using the EQ-5D
      questionnaire. MATERIAL AND METHODS: Adult subjects who were visiting patients in
      8 medical centers in Warsaw, Skierniewice, and Pulawy, were inter viewed during
      the Polish EQ-5D valuation study. Stratified quota sampling was used. The
      respondents completed the EQ-5D questionnaire and provided information on age,
      sex, marital status, education, employment, income, housing conditions, medical
      history, and smoking habits. The interviews were conducted between February and
      May 2008. RESULTS: The final sample (n = 317) was representative of the general
      Polish population with respect to age and sex. Moderate problems in at least 1
      dimension of the HRQoL were reported by 57% of the respondents, while extreme
      problems by 4.7%. Pain or discomfort was reported by 40% of the respondents,
      anxiety or depression by 38%. Problems with mobility were reported by 16% of the
      respondents, with usual activities (work, school) by 13%, and with self-care by
      3%. The mean state of health recorded on the visual analogue scale (VAS) was 81.6
      +/-14.4 points. The mean VAS value decreased from 87 and 91 points in the
      youngest age group to 67 and 72 points in the oldest age group, in men and women,
      respectively. CONCLUSIONS: Pain and anxiety are commonly reported problems in the
      Polish population, especially by young women. EQ-5D is a valuable tool for
      studying health outcomes and differences in health status within the Polish
      population.

PMID- 20693959
TI  - In vitro fertilization and stem cell harvesting from human embryos: the law and
      practice in the United States.
AB  - The challenges before science and medicine are these: science must explore the
      natural world as thoroughly as possible, while still honoring, protecting,
      serving and preserving the subject of its investigations, and the human beings
      for whom it is a tool; medicine must confront disease and disability as
      effectively as possible, while also honoring, protecting, and preserving those
      beings for whom it serves - all of those beings, not just some, or even most, at
      the potential expense of others. These goals are challenged by embryo-destructive
      human embryonic stem cell research. The human embryo is a human being as clearly
      defined by embryology, and as such should be protected by the codes governing
      human subject research. However, because of the "potential" benefits offered by
      pluripotent stem cells, coupled with abortion politics and a very poorly
      regulated infertility industry, United States governmental advisory commissions
      and the scientific, medical, and political communities have attempted to define
      away the humanity of the human embryo, with a few notable exceptions. Because
      infertility treatments in the United States are poorly regulated, there are large
      numbers of supernumerary embryos in cryopreservation. However, only a tiny
      portion of these will ever be potentially available for research, and thus are
      not a realistic source of the cells necessary to provide treatments to the
      millions who might benefit from proposed stem cell based therapies. Cloning will
      not be the answer either, given the millions of women who must be exploited to
      provide sufficient numbers of eggs to generate the cloned cell lines. Moreover,
      the disposition decisions parents must make for their extra embryos are often
      agonizing, and not uncommonly change. The use of supernumerary embryos as a
      source for human embryonic stem cells is unethical, will never be a sufficient
      source for the medical treatments expected from stem cell research, and is often
      a source of great distress for the conceiving parents. The United States
      experience is not a positive model for other countries to emulate.

PMID- 20693960
TI  - Antithrombotic therapy in anticoagulated patients with atrial fibrillation
      presenting with acute coronary syndromes and/or undergoing percutaneous coronary
      intervention/stenting.
AB  - The management of antithrombotic therapy in atrial fibrillation patients
      presenting with acute coronary syndrome and/or undergoing percutaneous coronary
      inter vention/stenting cannot be done according to a regimented common protocol,
      and stroke and bleeding risk stratification schema should be employed to
      individualize treatment options. A delicate balance is needed between the
      prevention of thromboembolism, against recurrent cardiac ischemia or stent
      thrombosis, and bleeding risk. New guidance from a consensus document of the
      European Society of Cardiology Working Group on Thrombosis, endorsed by the
      European Heart Rhythm Association and the European Association of Percutaneous
      Cardiovascular Interventions on the management of Antithrombotic Therapy in
      Atrial Fibrillation Patients Presenting with Acute Coronary Syndrome and/or
      Undergoing Percutaneous Coronary Intervention/Stenting has sought to clarify some
      of the major issues and problems surrounding this practice, and will allow
      clinicians to make much more informed decisions when faced with treating such
      patients.

PMID- 20693961
TI  - European Society of Cardiology 2009 guidelines for preoperative cardiac risk
      assessment and perioperative cardiac management in noncardiac surgery: key
      messages for clinical practice.
AB  - Patients undergoing noncardiac surgery are at risk of adverse perioperative and
      long-term outcome. When considering a patient for noncardiac surgery, a careful
      preoperative clinical risk evaluation and subsequent risk-reduction strategies
      are essential to reduce postoperative complications. To assist physicians with
      decision making, clinical guidelines are developed. The aim of clinical
      guidelines is to improve patient care by providing recommendations about
      appropriate healthcare in specific circumstances. Development of clinical
      guidelines is an important component in improving the quality of care. By
      translating the best available scientific evidence into specific recommendations,
      guidelines can serve as a useful tool to achieve effective and efficient patient
      care. In 2009, the first European Society of Cardiology guidelines on
      perioperative care were developed. This decisionmaking process integrates
      clinical markers, early coronary evaluation, functional capacity, and the type of
      surgery involved.

PMID- 20693962
TI  - KDIGO clinical practice guidelines for the diagnosis, evaluation, prevention, and
      treatment of mineral and bone disorders in chronic kidney disease.
AB  - KIDNEY DISEASE: Improving Global Outcomes (KDIGO) is an international nonprofit
      foundation established in 2003 to improve the care and outcomes of kidney disease
      patients worldwide through coordination of different initiatives to develop and
      implement clinical practice guidelines. After almost 4 years of intensive work,
      the mineral and bone disorder of chronic kidney disease guidelines were presented
      during the American Society of Nephrology Renal Week at the end of 2008, to be
      finally published in Kidney International, August 2009. In this paper, the main
      points of the guidelines are discussed: the diagnosis of biochemical, bone, and
      vascular abnormalities, the treatment targeted at lowering high serum phosphorus,
      the normalization of serum calcium, and, in dialysis patients, maintaining
      parathormone levels in the range of 2 to 9 times exceeding the normal limit.
      Because there are no randomized clinical trials that compare the efficacy and
      toxicity of different phosphate binders, vitamin D analogs, and calcimimetics,
      and there is no evidence that these drugs decrease mortality, the KDIGO experts
      do not make any specific recommendation in regard to these treatments. Finally,
      the guidelines for treatment of osteoporosis using bisphosphonates, and for
      evaluation and treatment of bone disease developing after the kidney transplant
      are presented in this review.

PMID- 20693963
TI  - Xenogenic cancer vaccines.
AB  - In the current review the latest literature data on design of cancer vaccines on
      the basis of xenogenic tumor-associated antigens and proteins that play an
      important role in tumor progression have been summarized. The main benefits and
      disadvantages of xenogenic cancer vaccines, the results of experimental studies
      and clinical trials, and perspectives of use are analyzed.

PMID- 20693964
TI  - Alcohol consumption and prostate cancer: a mini review.
AB  - Prostate cancer has become a major public health problem worldwide although the
      etiology of prostate cancer remains largely unknown. Dietary factors, dietary
      supplements, and physical activity might be important in the prevention of the
      disease. In the majority of studies published, it was observed that high
      consumption of meat, alcohol and dairy products has been linked to a greater
      risk. Specifically, alcohol use, and particularly heavy use, may cause cancers of
      liver, esophagus, larynx, pharynx and oral cavity, with risks for the aero
      digestive cancers. Moderate use among women has been related with increases in
      breast cancer. Alcohol consumption is a modifiable lifestyle factor that may
      affect prostate cancer risk. Alcohol alters the hormonal environment and in
      parallel, containing chemical substances such as flavonoids (red wine), may alter
      tumor cell growth. In this mini review, the relation between alcohol consumption
      and prostate cancer risk is analyzed.

PMID- 20693965
TI  - Genetic and epigenetic changes of NKIRAS1 gene in human renal cell carcinomas.
AB  - Renal cell carcinoma (RCC) is the most common malignant tumor of kidney
      associated with the worst clinical outcome. No molecular markers for RCC
      diagnostics and prognosis that could be applied in clinics were described yet.
      Large-scale screening of 3p human chromosome genes/loci in RCC and histologically
      normal tissues surrounding the tumors using NotI-microarray approach demonstrated
      that NKIRAS1 gene contained the largest percent of genetic/epigenetic changes in
      RCC tumor cells. AIM: To validate the results of NotI microarray analysis and
      study genetic, epigenetic changes, and the expression level of NKIRAS1 gene in
      human RCC samples. METHODS: DNA and RNA were isolated from freshly-frozen renal
      tumors' samples (n = 12) and from normal tissues surrounding the tumors.
      Epigenetic changes (methylation status) of NKIRAS1 were detected by bisulfite
      sequencing. Genetic changes and expression level were analyzed by Quantitative
      real-time PCR (qPCR) with SYBR Green. For relative quantification 2
      (DeltaDeltaCP) method was used. Nonparametric tests (Wilcoxon, Kruskal - Wallis
      and Mann - Whitney) were applied for statistical data analysis using the BioStat
      software. RESULTS: NKIRAS1 expression was downregulated in 75% of RCC samples (9
      of 12) compared with surrounding normal tissue. High grade tumors (3 and 4)
      showed lower expression of NKIRAS1 at the mRNA level than tumors of low grade (1
      and 2). No significant association was found between gene expression level and
      gender or age. Analysis of NKIRAS1 gene copy number was performed in 19 tumor
      samples. Changes in the copy number of NKIRAS1 gene were observed in 64% (9 of
      14) of cRCC samples. 9 samples displayed ratio (< 0.85 and >or= 0.35), thus were
      considered as hemizygous deletions. 3 samples showed ratio (> 0.85) and were
      considered as normal copy number. Changes in NKIRAS1 gene copy number were
      detected in all 3 benign oncocytomas, 1 papillary cancer and 1 sarcoma, where
      hemizygous deletion was observed. No changes in methylation status of NKIRAS1
      were found in RCC. CONCLUSIONS: We have validated the results of NotI microarray
      analysis of NKIRAS1 gene in RCC. It was shown the decreased expression level of
      NKIRAS1 in this type of tumor.

PMID- 20693966
TI  - Jurkat/A4 cells with multidrug resistance exhibit reduced sensitivity to
      quercetin.
AB  - BACKGROUND: While multidrug resistance of cancer cells is a well-known
      phenomenon, little is known on the cross resistance between cytotoxic
      chemotherapeutical agents and unrelated substances such as natural flavonoids.
      AIM: To compare the effects of cytotoxic drug, vepeside and natural flavonoid,
      quercetin in Jurkat cells and their multidrug-resistant subline Jurkat/A4, in
      particular to analyze the effector mechanisms of apoptosis and the profiles of
      several pro- and antiapoptotic proteins in these cells upon exposure to vepeside
      or quercetin. METHODS: Apoptosis and poly (ADP-ribose) polymerase cleavage were
      assessed by flow cytometry. Expression of apoptosis-related proteins was analyzed
      by Western blotting. RESULTS: Jurkat/A4 cells are less sensitive to
      antiproliferative effects of quercetin as compared with the parental Jurkat cell
      line. While vepeside as well as quercetin initially induces apoptosis in both
      cell lines, the following survival of the exposed cells is essentially different.
      In resistant Jurkat/A4 cells, vepeside or quercetin treatment activates
      significantly less caspase-9 and -3 as compared with that in the parental cells.
      The expression of Bad and BNip1 proteins in Jurkat/A4 cells is lower than in the
      parental cell line. At the same time, XIAP and CAS levels in Jurkat/A4 cells
      increase. Upon apoptosis induction, XIAP and CAS levels in Jurkat cells decrease,
      this effect being negligible in resistant cells. CONCLUSION: Multidrug-resistant
      Jurkat/A4 cells exhibit reduced sensitivity to cytotoxic effects of quercetin.
      The expression profile of Jurkat/A4 cells is characterized by the increased
      levels of XIAP and CAS representing the endogenous inhibitors of apoptosis.

PMID- 20693967
TI  - Immunocytochemical study of Bcr and Bcr-Abl localization in K562 cells.
AB  - AIM: To obtain polyclonal antibodies against recombinant proteins recognizing Bcr
      domain and fusion region of Bcr-Abl and analyze the patterns of intracellular
      distribution of Bcr and Bcr-Abl proteins in K562 cells of chronic myelogenous
      leukemia. METHODS: The coding sequences of DH and PH domains of Bcr-Abl were
      cloned, and the recombinant proteins were expressed in E. coli. The rabbit
      polyclonal antibodies were produced and used for immunocytochemical study of Bcr
      and Bcr-Abl localization in K562 cells. RESULTS: The gene constructs containing
      sequences coding for DH and PH domains of Bcr-Abl have been obtained. The
      antibodies with relative specificity to corresponding recombinant proteins differ
      by the patterns of their intracellular reactivity with Bcr- and Bcr-Abl related
      structures. While Bcr protein is located predominantly perinuclearly, antibody
      against hybrid Bcr-Abl protein is reacted with the structures in cell periphery,
      namely on cell membranes. CONCLUSION: Antibodies against DH and PH domains of Bcr
      Abl react with proteins located differently in chronic myelogenous leukemia
      cells. The difference in intracellular localization of Bcr and Bcr-Abl may be
      attributable to the different domains interacting with different multiprotein
      complexes.

PMID- 20693968
TI  - In vivo and In vitro effect of a nutrient mixture on human hepatocarcinoma cell
      line SK-HEP-1.
AB  - Long-term survival of patients with hepatocellular carcinoma (HCC), a common
      cancer worldwide, remains poor, due to metastasis and recurrence. AIM: To
      investigate the effect of a novel nutrient mixture (NM) containing ascorbic acid,
      lysine, proline, and green tea extract on human HCC cell line Sk-Hep-1 In vivo
      and In vitro. METHODS: After one week of isolation, 5-6 week old male athymic
      nude mice were inoculated with 3 x 10(6) SK-Hep-1 cells subcutaneously and
      randomly divided into two groups; group A was fed a regular diet and group B a
      regular diet supplemented with 0.5% NM. Four weeks later, the mice were
      sacrificed and their tumors were excised, weighed and processed for histology. We
      also tested the effect of NM In vitro on SK-Hep-1 cells, measuring cell
      proliferation by MTT assay, invasion through Matrigel, apoptosis by green caspase
      detection kit, MMP secretion by zymography, and morphology by H&E staining.
      RESULTS: NM inhibited tumor weight and burden of SK-Hep-1 xenografts by 42% and
      33% respectively. In vitro , NM exhibited 33% toxicity over the control at 500
      and 1,000 microg/ml concentration. Zymography demonstrated MMP-2 and MMP-9
      secretion which was inhibited by NM in a dose dependent fashion, with virtual
      total inhibition at 1000 microg/ml. Invasion through Matrigel was inhibited at
      100, 500 and 1,000 microg/ml by 53%, 83% and 100% respectively. NM induced slight
      apoptosis at 100 microg/ml, and profound apoptosis at 500 microg/ml and 1000
      microg/ml concentration. CONCLUSIONS: These results suggest that NM has
      therapeutic potential in treatment of HCC.

PMID- 20693969
TI  - The effect of NSC-631570 (ukrain) alone and in combination with pathogen
      associated molecules on cell cycle distribution and apoptosis induction of mouse
      melanoma cells with different biological properties.
AB  - Monotherapy and combined application of antitumor drug NSC-631570 (Ukrain) are
      successfully used for treatment of malignant melanoma since 1996. Melanoma cells
      of different origin have distinct susceptibility to components of Ukrain. AIM: To
      carry out comparative investigation of the effect of Ukrain used alone and in
      combination with pathogen associated molecules (PAM) on mitotic cycle and
      apoptosis induction in mouse melanoma cell lines with different biological
      properties. METHODS: Two cell lines with different biological properties (rate of
      cell division, level of hematogenous metastasis, sensitivity to tumor necrosis
      factor (TNF)-induced apoptosis) established from B16 mouse melanoma cell line,
      were used. Apoptosis induction and cell viability were analyzed using trypan blue
      exclusion test, morphological criteria, DNA gel electrophoresis and flow
      cytometry. Cell cycle distribution of tumor cells was determined by flow
      cytometry. Transporters associated with antigen processing (TAP) genes expression
      was analyzed using reverse transcriptase-polymerase chain reaction (RT-PCR)
      method. RESULTS: The melanoma cells with different metastatic capabilities
      differed markedly by the growth rate, sensitivity to apoptosis inducers, and the
      character of TAP gene expression. Treatment of melanoma cells with Ukrain
      resulted in apoptosis induction in a dose dependent manner. Melanoma cells with
      high-metastatic properties were more sensitive to Ukrain than their low
      metastatic variants. However combined use of drug with PAM induced apoptosis more
      effectively in melanoma cells with low-metastatic potential. CONCLUSION:
      Sensitivity to Ukrain in vitro may depend on biological properties of melanoma
      cells and may be modified by combined treatment of cells with TLR ligands. The
      results can be useful to optimize the regimen of mono and combined treatment of
      melanoma with Ukrain.

PMID- 20693970
TI  - The use of cardiac biomarkers in detection of cardiotoxicity associated with
      conventional and high-dose chemotherapy for acute leukemia.
AB  - AIM: Monitoring of cardiotoxicity of conventional and high-dose chemotherapy (HD
      CT) with multiple biomarkers of cardiac injury - glycogen phosphorylase BB
      (GPBB), heart-type fatty acid binding protein (H-FABP), cardiac troponins (cTnT,
      cTnI), creatine kinase MB (CK-MB mass), myoglobin. METHODS: A total of 47 adult
      acute leukemia patients were studied - 24 patients treated with conventional CT
      containing anthracyclines (ANT) and 23 patients treated with HD-CT (myeloablative
      preparative regimen) followed by hematopoietic cell transplantation (HCT).
      Cardiac biomarkers were assessed prior to treatment (before CT/HD-CT), after
      first CT with ANT, after last CT with ANT in the first group, after HD-CT and
      after HCT in the second group. Values above the reference range were considered
      elevated. RESULTS: Before CT/HD-CT, all biomarkers of cardiac injury were below
      the cut-offs in all patients. GPBB increased above the cut-off (7.30 microg/L) in
      4 (16.7%) patients after first CT and in 5 (20.8%) patients after last CT with
      ANT. GPBB increased above the cut-off in 5 (21.7%) patients after HD-CT and
      remained elevated in 5 (21.7%) patients after HCT. CTnI became elevated (above
      0.40 microg/L) in 2 (8.3%) patients after first and last CT with ANT. Both
      patients with cTnI positivity had elevated GPBB. Other tested biomarkers remained
      below the cut-offs during the study. CONCLUSION: Our results suggest that GPBB
      could become a sensitive biomarker for detection of acute cardiotoxicity
      associated with conventional CT containing ANT and HD-CT followed by HCT. The
      predictive value for development of cardiomyopathy in the future is not known and
      should be evaluated during a prospective follow-up. Based on our data, a larger
      prospective and multicenter study would be most desirable to define the potential
      role of new circulating biomarkers in the assessment of cardiotoxicity in
      oncology.

PMID- 20693971
TI  - Experimental study of antiangiogenic and photodynamic therapies combination for
      treatment of peritoneal carcinomatosis: preliminary results.
AB  - AIM: To create adequate orthotopic model of peritoneal carcinomatosis in rats
      using a transplantable rat tumor M-1 sarcoma, to assess the early tumor response
      after intraperitoneal photodynamic and/or antiangiogenic therapy for peritoneal
      carcinomatosis. METHODS: In 14-18 days after intraperitoneal inoculation,
      eighteen tumor-bearing animals were divided into three groups and undergone
      intraperitoneal photodynamic therapy and/or antiangiogenic therapy. Assessment of
      the tumor posttreatment changes was performed using a method of vital staining
      with Evans blue, MRI-monitoring and morphologic investigation. RESULTS:
      Percentage of necrosis in disseminated tumors of animals undergone combination
      therapy significantly higher then after each of the methods alone and achieved
      89.46% vs 41.47% after antiangiogenic therapy and 69.73% after photodynamic
      therapy. Contrast-enhanced MRI showed entirely necrotic tumor nodes in rats
      undergone the combination therapy. Morphologic study confirmed that tumor
      response after combination therapy was characterized by maximal spread of
      necrotic and inflammatory changes in tumor. CONCLUSION: Preliminary results
      demonstrate enhance of the treatment outcome after combination of antiangiogenic
      and intraperitoneal photodynamic therapies for peritoneal carcinomatosis in rats.

PMID- 20693972
TI  - Diffusion-weighted magnetic resonance imaging in non-invasive monitoring of
      antiangiogenic therapy in experimental tumor model.
AB  - AIM: To show usefulness of diffusion-weighted magnetic resonance imaging (MRI)
      for non-invasive assessment of experimental tumor after antiangiogenic treatment.
      METHODS: M1 sarcoma was implanted to the peritoneal cavity of the rat and allowed
      to grow to a palpable tumor size. Animal was treated with a single injection of
      endothelial growth factor antibody Bevacizumab (Avastin). Serial MRI scanning
      including diffusion-weighted sequence was performed before and up to 100 h after
      treatment. Animal was sacrificed thereafter and MRI data were correlated with
      morphology. RESULTS: Apparent diffusion coefficient (ADC) maps derived tumor
      necrotic area correlated well with histology-derived tumor necrotic area. ADC
      threshold of 1.39 x 10(-3) mm(2)/s appeared to be optimal for tumor necrosis
      quantification in this tumor model and allowed to follow temporal changes of
      tumor internal structure after treatment. CONCLUSION: Diffusion-weighted MRI
      permits non-invasive tissue characterization without the need for exogenous
      contrast agents and, therefore, may be used to individualise therapy and to
      monitor tumor response.

PMID- 20693973
TI  - Comparative investigation of the effect of ukrain on growth of ascites and solid
      forms of Ehrlich's carcinoma.
AB  - Ukrain (NSC-631570) is a cytostatic and immunomodulating semisynthetic compound
      of thiophosphate-modified alkaloids of Chelidonium majus L. It has selective
      cytotoxicity against cancer cells without healthy cells damaging. Dosage range,
      methods of introduction and duration of administration of the drug vary. AIM: To
      carry out comparative investigation of effect of Ukrain on growth of different
      form of Ehrlich's carcinoma. METHODS: Ehrlich's carcinoma cells were transplanted
      intraperitoneally and subcutaneously between the scapulas. Ukrain was
      administered intraperitoneally for 6 days (0.25 mg per mice of 20 g, it's 0.1
      LD50). The effect of drug on tumor growth was evaluated by the indexes of tumor
      growth inhibition (in the case of solid form), total number of tumor cells in
      ascites, number of viable tumor cells (in the case of ascitic form) and average
      life span of experimental animals. Cell cycle distribution of cancer cells was
      determined by flow cytometry. The number of circulating phagocytes was determined
      by flow cytometry with use of FITC-labelled S. aureus Cowan. RESULTS:
      Intraperitoneal Ukrain administration in mice with ascite form of Ehrlich's
      carcinoma resulted in moderate tumor growth retardation, but was accompanied by
      acute local inflammation and caused reduction of life span of experimental
      animals. In mice bearing solid form of Ehrlich's carcinoma treatment with Ukrain
      led to significant tumor growth inhibition and slight increase of life span. In
      mice bearing both of tumor variants treatment with drug caused restitution of the
      number of circulating phagocytes in peripheral blood, more expressed in mice
      bearing ascite tumor variant. CONCLUSION: Thus, anticancer activity of the Ukrain
      is more expressed in the case of solid variant of Ehrlich's carcinoma. This
      effect is mediated by direct apoptotic action of drug on Ehrlich's carcinoma
      cells and positive immunomodulating effect on tumor-bearing organism.

PMID- 20693974
TI  - Multidisciplinary approach in diagnosis of lung carcinoma.
AB  - AIM: To employ multidisciplinary approach in order to make the correct diagnosis
      of lung carcinoma clinically and morphologically mimicking lymphoma. METHODS:
      Immunostaining was performed by incubating tissue sections with appropriate
      antibodies, using the streptavidin-biotin technique. Antigen-antibody complexes
      were visualized with 3-amino-9-ethylcarbasole or diaminobenzidine hydrochloride
      substrate solution. We have investigated p53 gene mutations by polymerase chain
      reaction and DNA sequence analysis of exons 5, 6, 7, 8 and 9. RESULTS: Tumor
      cells expressed cytokeratin AE1/AE3, epithelial membrane antigen (EMA) and
      thyroid transcription factor-1 (TTF-1) without thyreoglobulin positivity.
      Further, tumor cells expressed neuroendocrine mar kers: synaptophysin,
      chromogranin A, neuron-specific enolase (NSE), CD56/NCAM, CD57/Leu-7 and protein
      gene product 9.5 (PGP9.5). P53 was also expressed. Diffuse large cell lymphomas
      of B and T cell origin were excluded. Direct sequencing analysis of exon 6 of the
      p53 gene revealed ATC to ACC mutation at codon 195. Final diagnosis of large cell
      lung neuroendocrine carcinoma (LCNEC) was established. CONCLUSIONS: Morphological
      pattern of tumor complied with large cell non-Hodgkin's lymphoma, but large cell
      lung carcinoma with neuroendocrine differentiation was proved
      immunohistochemically and confirmed by genetic analysis of p53 mutations in tumor
      tissue sample. Multidisciplinary approach in diagnosis of lung carcinoma is
      useful for its final diagnosis.

PMID- 20693975
TI  - Cancer prevention today: from healthy lifestyle and early detection to
      integrative multidisciplinary prevention and treatment.
AB  - Cancer prevention is recognized to be one the most efficient strategy in reducing
      cancer incidence and mortality. The world leading experts in the field of basic,
      clinical, epidemiologic and behavioral science presented their most innovative
      and promising findings and achievements during the Eighth Annual AACR
      International Conference on Frontiers in Cancer Prevention Research held from
      December 6-9, 2009, in Houston, TX, USA. In total around 800 participants from
      all over the world took an active part in the rich variety of the Conference
      session formats covering wide area of the most vital cancer research problems
      with strong emphasis on the early detection research, the latest developments in
      the tumor microenvironment, international prevention mechanisms, integrative
      prevention, targeted prevention and treatment, and efficient implementation of
      basic sciences into clinical practice.

PMID- 20693976
TI  - Risks of carcinogenesis from electromagnetic radiation of mobile telephony
      devices.
AB  - Intensive implementation of mobile telephony technology in everyday human life
      during last two decades has given a possibility for epidemiological estimation of
      long-term effects of chronic exposure of human organism to low-intensive
      microwave (MW) radiation. Latest epidemiological data reveal a significant
      increase in risk of development of some types of tumors in chronic (over 10
      years) users of mobile phone. It was detected a significant increase in incidence
      of brain tumors (glioma, acoustic neuroma, meningioma), parotid gland tumor,
      seminoma in long-term users of mobile phone, especially in cases of ipsilateral
      use (case-control odds ratios from 1.3 up to 6.1). Two epidemiological studies
      have indicated a significant increase of cancer incidence in people living close
      to the mobile telephony base station as compared with the population from distant
      area. These data raise a question of adequacy of modern safety limits of
      electromagnetic radiation (EMR) exposure for humans. For today the limits were
      based solely on the conception of thermal mechanism of biological effects of
      RF/MW radiation. Meantime the latest experimental data indicate the significant
      metabolic changes in living cell under the low-intensive (non-thermal) EMR
      exposure. Among reproducible biological effects of low-intensive MWs are reactive
      oxygen species overproduction, heat shock proteins expression, DNA damages,
      apoptosis. The lack of generally accepted mechanism of biological effects of low
      intensive non-ionizing radiation doesn't permit to disregard the obvious
      epidemiological and experimental data of its biological activity. Practical steps
      must be done for reasonable limitation of excessive EMR exposure, along with the
      implementation of new safety limits of mobile telephony devices radiation, and
      new technological decisions, which would take out the source of radiation from
      human brain.

PMID- 20693978
TI  - The FOXL2 C134W mutation is characteristic of adult granulosa cell tumors of the
      ovary.
AB  - Granulosa cell tumors of the ovary represent ~5% of malignant ovarian cancers. It
      has recently been reported that 95-97% of adult granulosa cell tumors carry a
      unique somatic mutation in the FOXL2 gene. We undertook this study to verify the
      presence of the FOXL2 Cys134Trp mutation in two geographically independent
      cohorts of granulosa cell tumors and to examine the expression pattern of FOXL2
      in these tumors. A total of 56 tumors with the histological diagnosis of adult
      granulosa cell tumor from two centers, Melbourne and Helsinki, were examined for
      the presence of the mutation using direct sequence analysis. Two granulosa cell
      tumor-derived cell lines, COV434 and KGN, three juvenile granulosa cell tumors
      and control tissues were also examined. The expression of the FOXL2 gene was
      determined using quantitative RT-PCR and/or immunohistochemistry. We found that
      52 of the 56 adult granulosa cell tumors harbor the mutation, of which three were
      hemi/homozygous. Of the four cases with wild-type FOXL2 sequence, reappraisal
      suggests that three may have been misclassified at primary diagnosis. The KGN
      cells were heterozygous for the mutation, whereas the COV434 cells had a wild
      type FOXL2 genotype. The expression levels of FOXL2 were similar across the adult
      granulosa cell tumors and the normal ovary controls; one mutation-negative
      granulosa cell tumor had high FOXL2 mRNA levels, whereas the COV434 cells and two
      of the three juvenile granulosa cell tumors lacked the expression of FOXL2. Our
      data provide confirmation of the frequent presence of the FOXL2 C134W mutation in
      adult granulosa cell tumors and demonstrate that the mutation is not associated
      with altered FOXL2 expression. The mutation analysis may be a useful tool to
      differentiate particularly between cell-rich diffuse granulosa cell tumors and
      mitotically active sex cord-stromal tumors. This unique FOXL2 mutation appears to
      be characteristic of adult granulosa cell tumors.

PMID- 20693977
TI  - Regulation of DNA-damage responses and cell-cycle progression by the chromatin
      remodelling factor CHD4.
AB  - The chromatin remodelling factor chromodomain helicase DNA-binding protein 4
      (CHD4) is a catalytic subunit of the NuRD transcriptional repressor complex.
      Here, we reveal novel functions for CHD4 in the DNA-damage response (DDR) and
      cell-cycle control. We show that CHD4 mediates rapid poly(ADP-ribose)-dependent
      recruitment of the NuRD complex to DNA-damage sites, and we identify CHD4 as a
      phosphorylation target for the apical DDR kinase ataxia-telangiectasia mutated.
      Functionally, we show that CHD4 promotes repair of DNA double-strand breaks and
      cell survival after DNA damage. In addition, we show that CHD4 acts as an
      important regulator of the G1/S cell-cycle transition by controlling p53
      deacetylation. These results provide new insights into how the chromatin
      remodelling complex NuRD contributes to maintaining genome stability.

PMID- 20693979
TI  - ETS family-associated gene fusions in Japanese prostate cancer: analysis of 194
      radical prostatectomy samples.
AB  - The incidence and clinical significance of the TMPRSS2:ERG gene fusion in
      prostate cancer has been investigated with contradictory results. It is now
      common knowledge that significant variability in gene alterations exists
      according to ethnic background in various kinds of cancer. In this study, we
      evaluated gene fusions involving the ETS gene family in Japanese prostate cancer.
      Total RNA from 194 formalin-fixed and paraffin-embedded prostate cancer samples
      obtained by radical prostatectomy was subjected to reverse-transcriptase
      polymerase chain reaction to detect the common TMPRSS2:ERG T1-E4 and T1-E5 fusion
      transcripts and five other non-TMPRSS2:ERG fusion transcripts. We identified 54
      TMPRSS2:ERG-positive cases (54/194, 28%) and two HNRPA2B1:ETV1-positive cases
      (2/194, 1%). The SLC45A3-ELK4 transcript, a fusion transcript without structural
      gene rearrangement, was detectable in five cases (5/194, 3%). The frequencies of
      both TMPRSS2:ERG- and non-TMPRSS2:ERG-positive cases were lower than those
      reported for European, North American or Brazilian patients. Internodular
      heterogeneity of TMPRSS2:ERG was observed in 5 out of 11 multifocal cases (45%);
      a frequency similar to that found in European and North American cases. We found
      a positive correlation between the TMPRSS2:ERG fusion and a Gleason score of <=7
      and patient age, but found no relationship with pT stage or plasma prostate
      specific antigen concentration. To exclude the possibility that Japanese prostate
      cancer displays novel TMPRSS2:ERG transcript variants or has unique 5' fusion
      partners for the ETS genes, we performed 5' RACE using fresh-frozen prostate
      cancer samples. We identified only the normal 5' cDNA ends for ERG, ETV1 and ETV5
      in fusion-negative cases. Because we identified a relatively low frequency of
      TMPRSS2:ERG and other fusions, further evaluation is required before this
      promising molecular marker should be introduced into the management of Japanese
      prostate cancer patients.

PMID- 20693980
TI  - A novel kind of tumor type-characteristic junction: plakophilin-2 as a major
      protein of adherens junctions in cardiac myxomata.
AB  - Using novel antibodies of high avidity to--and specificity for--the constitutive
      desmosomal plaque protein, plakophilin-2 (Pkp2), in a systematic study of the
      molecular composition of junctions connecting the cells of soft tissue tumors, we
      have discovered with immunocytochemical, biochemical and electron microscopical
      methods, a novel type of adherens junctions in all 32 cardiac myxomata examined.
      These junctions contain cadherin-11 as their major transmembrane glycoprotein,
      which we could repeatedly show in colocalization with N-cadherin, anchored in a
      cytoplasmic plaque formed by alpha- and beta-catenin, together with the further
      armadillo-type proteins plakoglobin, p120, p0071 and ARVCF. Surprisingly, all
      adherens junctions of these tumors contained, in addition, another major
      armadillo protein Pkp2, hitherto known as an obligatory and characteristic
      constituent of desmosomes in epithelium-derived tumors. We have not detected Pkp2
      in a series of noncardiac myxomata studied in parallel. Therefore, we conclude
      that this acquisition of Pkp2, which we have recently also observed in some
      mesenchymally derived cells growing in culture, can also occur in tumorigenic
      transformations in situ. We propose to examine the marker value of Pkp2 in
      clinical diagnoses of cardiac myxomata and to develop Pkp2-targeted therapeutic
      reagents.

PMID- 20693981
TI  - TIMP-4 and CD63: new prognostic biomarkers in human astrocytomas.
AB  - Based on the molecular profiling of astrocytomas, we previously identified a
      series of genes involved in astrocytoma invasion. Of these, tissue inhibitor of
      metalloproteinase-4 (TIMP-4) was found to be overexpressed in pilocytic
      astrocytomas relative to diffuse astrocytomas of any histological grade. Although
      some data suggest that TIMP-4 may be an anti-tumoral actor in astrocytomas,
      recent findings challenge this concept. The present study aims to investigate the
      diagnostic and prognostic values of TIMP-4 and its putative partner CD63 in human
      astrocytomas. Tissue microarray and image analysis were first carried out to
      quantitatively analyze the immunohistochemical expression of these proteins in
      471 gliomas including 354 astrocytomas. Pathological semi-quantitative scores of
      both markers' expression were then established and correlated to astrocytoma
      diagnosis and patient prognosis. TIMP-4 and CD63 expressions were both
      overexpressed in astrocytomas compared with oligodendrogliomas (P<0.001) and in
      pilocytic astrocytomas compared with grade II diffuse astrocytomas (P<0.001). In
      glioblastomas, high TIMP-4/CD63 co-expression scores were identified as
      independent prognostic factors associated with progression and shorter survival.
      In conclusion, this work provides the first evidence of a TIMP-4/CD63 association
      in astrocytoma tumor cells. It identifies TIMP-4 and CD63 as markers of the
      astrocytic phenotype in patients with gliomas. In addition, this work highlights
      the contribution of high TIMP-4/CD63 co-expression to the adverse outcomes of
      patients with glioblastomas.

PMID- 20693982
TI  - ERG rearrangement is present in a subset of transition zone prostatic tumors.
AB  - A majority of prostate cancers exhibit a recurrent gene rearrangement involving
      chromosome 21. In approximately 90% of cases, the rearrangement is characterized
      by fusion of the androgen-regulated gene TMPRSS2 with the oncogene ERG. A recent
      study suggested that TMPRSS2-ERG gene fusion is lacking in cancers arising from
      the transition zone of the prostate. A dominant transition zone cancer was
      detected in 62/397 (16%) patients who underwent radical prostatectomy at our
      institution and were reviewed and mapped by a single pathologist. In 46/62
      specimens, a secondary tumor was identified in the peripheral zone of the
      prostate. A tissue microarray containing both transition and peripheral zone
      tumors was constructed and evaluated for gene fusion analysis. TMPRSS2-ERG fusion
      status was determined using a multicolor interphase fluorescence in situ
      hybridization assay for ERG break-apart. The median age of the patients was 59
      years. Prostatectomy Gleason score was 6 in 21, 7 in 34, and >=8 in 7 cases.
      Median tumor volume was 200 mm(2). TMPRSS2-ERG gene fusion was present in 7/59
      (12%) transition zone, and in 12/35 (34%) peripheral zone tumors. Transition zone
      fusion-positive cases were larger than their negative counterparts. No
      significant correlation was found between fusion status and Gleason score or
      pathologic stage. Gene fusion through deletion occurred in 4/7 transition zone
      and 7/12 peripheral zone tumors. Transition zone prostate cancers are considered
      biologically and genetically different from peripheral zone tumors. Although ERG
      rearrangement is more common in peripheral zone tumors, we have detected TMPRSS2
      ERG fusion in a subset of transition zone cancers (12%). The lower frequency of
      gene fusion in transition zone prostate cancer may suggest distinct molecular
      alterations from peripheral zone tumors and the association with a high tumor
      volume may indicate a growth advantage for transition zone tumors harboring the
      gene fusion. Further studies are necessary to confirm this hypothesis.

PMID- 20693983
TI  - beta-catenin/Wnt signalling pathway in fibromatosis, metaplastic carcinomas and
      phyllodes tumours of the breast.
AB  - Wnt signalling pathway is known to have a critical role in carcinogenesis and in
      epithelial-to-mesenchymal transition. Upon Wnt activation, beta-catenin is
      translocated from the membrane to the cytoplasm and nucleus, where it interacts
      with transcriptional activators. It has been suggested that various spindle cell
      lesions of the breast may harbour Wnt pathway activation. Given that beta-catenin
      nuclear localization constitutes a good surrogate marker of Wnt canonical pathway
      activation, we have investigated the distribution of beta-catenin in spindle cell
      lesions of the breast and whether it could be employed in the differential
      diagnosis of these lesions. A total of 52 metaplastic breast carcinomas, eight
      fibromatoses and 23 phyllodes tumours were retrieved from our institutions'
      archives. We performed immunohistochemistry using two anti-beta-catenin
      antibodies. In all, three fibromatoses and 21 metaplastic breast carcinomas were
      subjected to CTNNB1 (beta-catenin encoding gene) mutation analysis by direct gene
      sequencing. A good correlation between the two antibodies was observed
      (Spearman's r>0.82, P<0.001). All fibromatoses and 23% of metaplastic breast
      carcinomas expressed nuclear beta-catenin. In fibromatosis, beta-catenin was more
      often diffusely expressed, whereas in metaplastic breast carcinomas, expression
      was more frequently focal. Membranous beta-catenin expression was significantly
      lower in spindle cell carcinomas than in other subtypes of metaplastic breast
      carcinomas. In phyllodes tumours, stromal cells of benign and malignant subtypes
      displayed nuclear beta-catenin expression in 94 and 57% of cases, respectively.
      No CTNNB1 mutation was identified in any of the 21 metaplastic carcinomas
      analysed, whereas the mutations 45S>S/P and 41T>T/A were found in samples of
      fibromatosis. In conclusion, beta-catenin nuclear expression is a common feature
      in fibromatoses and in the stromal component of phyllodes tumours, but may also
      be observed in metaplastic breast carcinomas. beta-catenin nuclear expression
      should not be used as a single marker to differentiate fibromatosis from other
      spindle cell tumours of the breast.

PMID- 20693984
TI  - Using oligonucleotide aptamer probes for immunostaining of formalin-fixed and
      paraffin-embedded tissues.
AB  - For tissue immunostaining, antibodies are currently the only clinically validated
      and commercially available probes. Aptamers, which belong to a class of small
      molecule ligands composed of short single-stranded oligonucleotides, have emerged
      as probes over the last several decades; however, their potential clinical value
      has not yet been fully explored. Using cultured cells and an RNA-based CD30
      aptamer, we recently demonstrated that the synthetic aptamer is useful as a
      specific probe for flow cytometric detection of CD30-expressing lymphoma cells.
      In this study, we further validated the use of this aptamer probe for
      immunostaining of formalin-fixed and paraffin-embedded lymphoma tissues. Using
      CD30 antibody as a standard control, we demonstrated that the synthetic CD30
      aptamer specifically recognized and immunostained tumor cells of classical
      Hodgkin lymphoma and anaplastic large cell lymphoma, but did not react with
      background cells within tumor sites. Notably, the CD30 aptamer probe optimally
      immunostained lymphoma cells with lower temperature antigen retrieval (37 vs 96
      degrees C for antibody) and shorter probing reaction times (20 vs 90 min for
      antibody) than typical antibody immunostaining protocols. In addition, the CD30
      aptamer probe showed no nonspecific background staining of cell debris in
      necrotic tissue and exhibited no cross-reaction to tissues that do not express
      CD30, as confirmed by a standard CD30 antibody staining. Therefore, our findings
      indicate that the synthetic oligonucleotide CD30 aptamer can be used as a probe
      for immunostaining of fixed tissue sections for disease diagnosis.

PMID- 20693985
TI  - Epidermal growth factor receptor in adrenocortical tumors: analysis of gene
      sequence, protein expression and correlation with clinical outcome.
AB  - Adrenocortical carcinoma is a rare but highly malignant neoplasm with still
      limited treatment options. Epidermal growth factor receptor (EGFR) has been shown
      to be overexpressed in many solid tumors, but its expression in adrenocortical
      carcinoma has been studied only in a limited number of cases. Therefore, we
      analyzed the expression of EGFR in 169 adrenocortical carcinoma samples and
      compared it with 31 adrenocortical adenomas. Additionally, in 30 cases of
      adrenocortical carcinoma, exons 18-21 of the EGFR gene were cloned and sequenced.
      EGFR expression was found in 128 of 169 adrenocortical carcinoma samples (76%),
      and in 60 of these samples (=36%) strong membrane staining was detected. However,
      there was no significant correlation with clinical outcome. In addition, all 30
      sequenced cases revealed unmutated EGFR genes. In contrast, only 1 out of 31
      adrenocortical adenomas weakly expressed the EGFR (3%). In summary, EGFR was
      overexpressed in more than three-quarters of adrenocortical carcinoma cases of
      this series. However, no mutations of the EGFR gene were found and EGFR
      expression was not of prognostic relevance. As EGFR is hardly expressed in
      adrenocortical adenomas, our results suggest that its expression in
      adrenocortical tumors indicates a malignant phenotype, which may be used in the
      differential diagnosis between adrenocortical adenomas and carcinomas.

PMID- 20693987
TI  - OncomiR addiction in an in vivo model of microRNA-21-induced pre-B-cell lymphoma.
AB  - MicroRNAs (miRNAs) belong to a recently discovered class of small RNA molecules
      that regulate gene expression at the post-transcriptional level. miRNAs have
      crucial functions in the development and establishment of cell identity, and
      aberrant metabolism or expression of miRNAs has been linked to human diseases,
      including cancer. Components of the miRNA machinery and miRNAs themselves are
      involved in many cellular processes that are altered in cancer, such as
      differentiation, proliferation and apoptosis. Some miRNAs, referred to as
      oncomiRs, show differential expression levels in cancer and are able to affect
      cellular transformation, carcinogenesis and metastasis, acting either as
      oncogenes or tumour suppressors. The phenomenon of 'oncogene addiction' reveals
      that despite the multistep nature of tumorigenesis, targeting of certain single
      oncogenes can have therapeutic value, and the possibility of oncomiR addiction
      has been proposed but never demonstrated. MicroRNA-21 (miR-21) is a unique miRNA
      in that it is overexpressed in most tumour types analysed so far. Despite great
      interest in miR-21, most of the data implicating it in cancer have been obtained
      through miRNA profiling and limited in vitro functional assays. To explore the
      role of miR-21 in cancer in vivo, we used Cre and Tet-off technologies to
      generate mice conditionally expressing miR-21. Here we show that overexpression
      of miR-21 leads to a pre-B malignant lymphoid-like phenotype, demonstrating that
      mir-21 is a genuine oncogene. When miR-21 was inactivated, the tumours regressed
      completely in a few days, partly as a result of apoptosis. These results
      demonstrate that tumours can become addicted to oncomiRs and support efforts to
      treat human cancers through pharmacological inactivation of miRNAs such as miR
      21.

PMID- 20693986
TI  - MICU1 encodes a mitochondrial EF hand protein required for Ca(2+) uptake.
AB  - Mitochondrial calcium uptake has a central role in cell physiology by stimulating
      ATP production, shaping cytosolic calcium transients and regulating cell death.
      The biophysical properties of mitochondrial calcium uptake have been studied in
      detail, but the underlying proteins remain elusive. Here we use an integrative
      strategy to predict human genes involved in mitochondrial calcium entry based on
      clues from comparative physiology, evolutionary genomics and organelle
      proteomics. RNA interference against 13 top candidates highlighted one gene,
      CBARA1, that we call hereafter mitochondrial calcium uptake 1 (MICU1). Silencing
      MICU1 does not disrupt mitochondrial respiration or membrane potential but
      abolishes mitochondrial calcium entry in intact and permeabilized cells, and
      attenuates the metabolic coupling between cytosolic calcium transients and
      activation of matrix dehydrogenases. MICU1 is associated with the mitochondrial
      inner membrane and has two canonical EF hands that are essential for its
      activity, indicating a role in calcium sensing. MICU1 represents the founding
      member of a set of proteins required for high-capacity mitochondrial calcium
      uptake. Its discovery may lead to the complete molecular characterization of
      mitochondrial calcium uptake pathways, and offers genetic strategies for
      understanding their contribution to normal physiology and disease.

PMID- 20693988
TI  - Very large magnetoresistance in graphene nanoribbons.
AB  - Graphene has unique electronic properties, and graphene nanoribbons are of
      particular interest because they exhibit a conduction bandgap that arises due to
      size confinement and edge effects. Theoretical studies have suggested that
      graphene nanoribbons could have interesting magneto-electronic properties, with a
      very large predicted magnetoresistance. Here, we report the experimental
      observation of a significant enhancement in the conductance of a graphene
      nanoribbon field-effect transistor by a perpendicular magnetic field. A negative
      magnetoresistance of nearly 100% was observed at low temperatures, with over 50%
      magnetoresistance remaining at room temperature. This magnetoresistance can be
      tuned by varying the gate or source-drain bias. We also find that the charge
      transport in the nanoribbons is not significantly modified by an in-plane
      magnetic field. The large observed values of magnetoresistance may be attributed
      to the reduction of quantum confinement through the formation of cyclotron orbits
      and the delocalization effect under the perpendicular magnetic field.

PMID- 20693989
TI  - Repeated administrations of carbon nanotubes in male mice cause reversible testis
      damage without affecting fertility.
AB  - Soluble carbon nanotubes show promise as materials for in vivo delivery and
      imaging applications. Several reports have described the in vivo toxicity of
      carbon nanotubes, but their effects on male reproduction have not been examined.
      Here, we show that repeated intravenous injections of water-soluble multiwalled
      carbon nanotubes into male mice can cause reversible testis damage without
      affecting fertility. Nanotubes accumulated in the testes, generated oxidative
      stress and decreased the thickness of the seminiferous epithelium in the testis
      at day 15, but the damage was repaired at 60 and 90 days. The quantity, quality
      and integrity of the sperm and the levels of three major sex hormones were not
      significantly affected throughout the 90-day period. The fertility of treated
      male mice was unaffected; the pregnancy rate and delivery success of female mice
      that mated with the treated male mice did not differ from those that mated with
      untreated male mice.

PMID- 20693990
TI  - Nanomechanical mass sensing and stiffness spectrometry based on two-dimensional
      vibrations of resonant nanowires.
AB  - One-dimensional nanomechanical resonators based on nanowires and nanotubes have
      emerged as promising candidates for mass sensors. When the resonator is clamped
      at one end and the atoms or molecules being measured land on the other end (which
      is free to vibrate), the resonance frequency of the device decreases by an amount
      that is proportional to the mass of the atoms or molecules. However, atoms and
      molecules can land at any position along the resonator, and many biomolecules
      have sizes that are comparable to the size of the resonator, so the relationship
      between the added mass and the frequency shift breaks down. Moreover, whereas
      resonators fabricated by top-down methods tend to vibrate in just one dimension
      because they are usually shaped like diving boards, perfectly axisymmetric one
      dimensional nanoresonators can support flexural vibrations with the same
      amplitude and frequency in two dimensions. Here, we propose a new approach to
      mass sensing and stiffness spectroscopy based on the fact that the nanoresonator
      will enter a superposition state of two orthogonal vibrations with different
      frequencies when this symmetry is broken. Measuring these frequencies allows the
      mass, stiffness and azimuthal arrival direction of the adsorbate to be
      determined.

PMID- 20693991
TI  - Zinc availability regulates exit from meiosis in maturing mammalian oocytes.
AB  - Cellular metal ion fluxes are known in alkali and alkaline earth metals but are
      not well documented in transition metals. Here we describe major changes in the
      zinc physiology of the mammalian oocyte as it matures and initiates embryonic
      development. Single-cell elemental analysis of mouse oocytes by synchrotron-based
      X-ray fluorescence microscopy (XFM) revealed a 50% increase in total zinc content
      within the 12-14-h period of meiotic maturation. Perturbation of zinc homeostasis
      with a cell-permeable small-molecule chelator blocked meiotic progression past
      telophase I. Zinc supplementation rescued this phenotype when administered before
      this meiotic block. However, after telophase arrest, zinc triggered
      parthenogenesis, suggesting that exit from this meiotic step is tightly regulated
      by the availability of a zinc-dependent signal. These results implicate the zinc
      bolus acquired during meiotic maturation as an important part of the maternal
      legacy to the embryo.

PMID- 20693992
TI  - Biotin synthesis begins by hijacking the fatty acid synthetic pathway.
AB  - Although biotin is an essential enzyme cofactor found in all three domains of
      life, our knowledge of its biosynthesis remains fragmentary. Most of the carbon
      atoms of biotin are derived from pimelic acid, a seven-carbon dicarboxylic acid,
      but the mechanism whereby this intermediate is assembled remains unknown. Genetic
      analysis in Escherichia coli identified only two genes of unknown function
      required for pimelate synthesis, bioC and bioH. We report in vivo and in vitro
      evidence that the pimeloyl moiety is synthesized by a modified fatty acid
      synthetic pathway in which the omega-carboxyl group of a malonyl-thioester is
      methylated by BioC, which allows recognition of this atypical substrate by the
      fatty acid synthetic enzymes. The malonyl-thioester methyl ester enters fatty
      acid synthesis as the primer and undergoes two reiterations of the fatty acid
      elongation cycle to give pimeloyl-acyl carrier protein (ACP) methyl ester, which
      is hydrolyzed to pimeloyl-ACP and methanol by BioH.

PMID- 20693994
TI  - Low-field magnetoelectric effect at room temperature.
AB  - The discoveries of gigantic ferroelectric polarization in BiFeO(3) (ref. 1) and
      ferroelectricity accompanied by a magnetic order in TbMnO(3) (ref. 2) have
      renewed interest in research on magnetoelectric multiferroics, materials in which
      magnetic and ferroelectric orders coexist, from both fundamental and
      technological points of view. Among several different types of magnetoelectric
      multiferroic, magnetically induced ferroelectrics in which ferroelectricity is
      induced by complex magnetic orders, such as spiral orders, exhibit giant
      magnetoelectric effects, remarkable changes in electric polarization in response
      to a magnetic field. Many magnetically induced ferroelectrics showing the
      magnetoelectric effects have been found in the past several years. From a
      practical point of view, however, their magnetoelectric effects are useless
      because they operate only far below room temperature (for example, 28 K in
      TbMnO(3) (ref. 2) and 230 K in CuO (ref. 11)). Furthermore, in most of them, the
      operating magnetic field is an order of tesla that is too high for practical
      applications. Here we report materials, Z-type hexaferrites, overcoming these
      problems on magnetically induced ferroelectrics. The best magnetoelectric
      properties were obtained for Sr(3)Co(2)Fe(24)O(41) ceramics sintered in oxygen,
      which exhibit a low-field magnetoelectric effect at room temperature. Our result
      represents an important step towards practical device applications using the
      magnetoelectric effects.

PMID- 20693993
TI  - Transgenic mice with a diverse human T cell antigen receptor repertoire.
AB  - Because of tolerance mechanisms, it has been hard to identify the T cell
      receptors (TCRs) of high-avidity T cells against self (for example, tumor)
      antigens. TCRs that are specific for foreign human antigens from the nontolerant
      T cell repertoire can be identified in mice. Moreover, if mice are constructed to
      express the human TCR repertoire, they can be used to analyze the unskewed
      repertoire against human self antigens. Here we generated transgenic mice with
      the entire human TCRalphabeta gene loci (1.1 and 0.7 Mb), whose T cells express a
      diverse human TCR repertoire that compensates for mouse TCR deficiency. A human
      major histocompatibility class I transgene increases the generation of CD8+ T
      cells with human compared to mouse TCRs. Functional CD8+ T cells against several
      human tumor antigens were induced, and those against the Melan-A melanoma antigen
      used similar TCRs to those that have been detected in T cell clones from
      individuals with autoimmune vitiligo or melanoma. These mice will allow
      researchers to identify pathogenic and therapeutic human TCRs.

PMID- 20693995
TI  - Designer spoof surface plasmon structures collimate terahertz laser beams.
AB  - Surface plasmons have found a broad range of applications in photonic devices at
      visible and near-infrared wavelengths. In contrast, longer-wavelength surface
      electromagnetic waves, known as Sommerfeld or Zenneck waves, are characterized by
      poor confinement to surfaces and are therefore difficult to control using
      conventional metallo-dielectric plasmonic structures. However, patterning the
      surface with subwavelength periodic features can markedly reduce the asymptotic
      surface plasmon frequency, leading to 'spoof' surface plasmons with subwavelength
      confinement at infrared wavelengths and beyond, which mimic surface plasmons at
      much shorter wavelengths. We demonstrate that by directly sculpting designer
      spoof surface plasmon structures that tailor the dispersion of terahertz surface
      plasmon polaritons on the highly doped semiconductor facets of terahertz quantum
      cascade lasers, the performance of the lasers can be markedly enhanced. Using a
      simple one-dimensional grating design, the beam divergence of the lasers was
      reduced from approximately 180 degrees to approximately 10 degrees, the
      directivity was improved by over 10 decibels and the power collection efficiency
      was increased by a factor of about six compared with the original unpatterned
      devices. We achieve these improvements without compromising high-temperature
      performance of the lasers.

PMID- 20693996
TI  - CellCognition: time-resolved phenotype annotation in high-throughput live cell
      imaging.
AB  - Fluorescence time-lapse imaging has become a powerful tool to investigate complex
      dynamic processes such as cell division or intracellular trafficking. Automated
      microscopes generate time-resolved imaging data at high throughput, yet tools for
      quantification of large-scale movie data are largely missing. Here we present
      CellCognition, a computational framework to annotate complex cellular dynamics.
      We developed a machine-learning method that combines state-of-the-art
      classification with hidden Markov modeling for annotation of the progression
      through morphologically distinct biological states. Incorporation of time
      information into the annotation scheme was essential to suppress classification
      noise at state transitions and confusion between different functional states with
      similar morphology. We demonstrate generic applicability in different assays and
      perturbation conditions, including a candidate-based RNA interference screen for
      regulators of mitotic exit in human cells. CellCognition is published as open
      source software, enabling live-cell imaging-based screening with assays that
      directly score cellular dynamics.

PMID- 20693997
TI  - Two-photon high-resolution measurement of partial pressure of oxygen in cerebral
      vasculature and tissue.
AB  - Measurements of oxygen partial pressure (pO(2)) with high temporal and spatial
      resolution in three dimensions is crucial for understanding oxygen delivery and
      consumption in normal and diseased brain. Among existing pO(2) measurement
      methods, phosphorescence quenching is optimally suited for the task. However,
      previous attempts to couple phosphorescence with two-photon laser scanning
      microscopy have faced substantial difficulties because of extremely low two
      photon absorption cross-sections of conventional phosphorescent probes. Here we
      report to our knowledge the first practical in vivo two-photon high-resolution
      pO(2) measurements in small rodents' cortical microvasculature and tissue, made
      possible by combining an optimized imaging system with a two-photon-enhanced
      phosphorescent nanoprobe. The method features a measurement depth of up to 250
      microm, sub-second temporal resolution and requires low probe concentration. The
      properties of the probe allowed for direct high-resolution measurement of
      cortical extravascular (tissue) pO(2), opening many possibilities for functional
      metabolic brain studies.

PMID- 20693998
TI  - Live-cell super-resolution imaging with trimethoprim conjugates.
AB  - The spatiotemporal resolution of subdiffraction fluorescence imaging has been
      limited by the difficulty of labeling proteins in cells with suitable
      fluorophores. Here we report a chemical tag that allows proteins to be labeled
      with an organic fluorophore with high photon flux and fast photoswitching
      performance in live cells. This label allowed us to image the dynamics of human
      histone H2B protein in living cells at approximately 20 nm resolution.

PMID- 20693999
TI  - Spontaneous network activity visualized by ultrasensitive Ca(2+) indicators,
      yellow Cameleon-Nano.
AB  - We report ultrasensitive Ca(2+) indicators, yellow cameleon-Nano (YC-Nano),
      developed by engineering the Ca(2+)-sensing domain of a genetically encoded
      Ca(2+) indicator, YC2.60 or YC3.60. Their high Ca(2+) affinities (K(d) = 15-140
      nM) and large signal change (1,450%) enabled detection of subtle Ca(2+)
      transients associated with intercellular signaling dynamics and neuronal
      activity, even in 100,000-cell networks. These indicators will be useful for
      studying information processing in living multicellular networks.

PMID- 20694000
TI  - Dissecting the molecular architecture of integrin adhesion sites by cryo-electron
      tomography.
AB  - Focal adhesions are integrin-based multiprotein complexes, several micrometres in
      diameter, that mechanically link the extracellular matrix with the termini of
      actin bundles. The molecular diversity of focal adhesions and their role in cell
      migration and matrix sensing has been extensively studied, but their
      ultrastructural architecture is still unknown. We present the first three
      dimensional structural reconstruction of focal adhesions using cryo-electron
      tomography. Our analyses reveal that the membrane-cytoskeleton interaction at
      focal adhesions is mediated through particles located at the cell membrane and
      attached to actin fibres. The particles have diameters of 25 +/- 5 nm, and an
      average interspacing of approximately 45 nm. Treatment with the Rho-kinase
      inhibitor Y-27632 induces a rapid decrease in particle diameter, suggesting that
      they are highly mechanosensitive. Our findings clarify the internal architecture
      of focal adhesions at molecular resolution, and provide insights into their
      scaffolding and mechanosensory functions.

PMID- 20694001
TI  - A calcineurin/AKAP complex is required for NMDA receptor-dependent long-term
      depression.
AB  - AKAP79/150 is a protein scaffold that is thought to position specific kinases
      (protein kinase A and C) and phosphatases (calcineurin) in appropriate synaptic
      domains so that their activities can regulate excitatory synaptic strength. Using
      a viral-mediated molecular replacement strategy in rat hippocampal slices, we
      found that AKAP is required for NMDA receptor-dependent long-term depression
      solely because of its interaction with calcineurin.

PMID- 20694002
TI  - GABAergic circuits control stimulus-instructed receptive field development in the
      optic tectum.
AB  - During the development of sensory systems, receptive fields are modified by
      stimuli in the environment. This is thought to rely on learning algorithms that
      are sensitive to correlations in spike timing between cells, but the manner in
      which developing circuits selectively exploit correlations that are related to
      sensory inputs is unknown. We recorded from neurons in the developing optic
      tectum of Xenopus laevis and found that repeated presentation of moving visual
      stimuli induced receptive field changes that reflected the properties of the
      stimuli and that this form of learning was disrupted when GABAergic transmission
      was blocked. Consistent with a role for spike timing-dependent mechanisms, GABA
      blockade altered spike-timing patterns in the tectum and increased correlations
      between cells that would affect plasticity at intratectal synapses. This is a
      previously unknown role for GABAergic signals in development and highlights the
      importance of regulating the statistics of spiking activity for learning.

PMID- 20694003
TI  - SRF binding to SRE 6.9 in the Arc promoter is essential for LTD in cultured
      Purkinje cells.
AB  - It has been suggested that gene expression and protein synthesis are required for
      both long-term memory consolidation and late phases of long-term potentiation and
      long-term depression (LTD). The necessary genes and the specific transcription
      factor binding sites in their promoters remain unknown. We found that inhibition
      of the transcription factor SRF or its cofactor MAL blocked the late phase of LTD
      in mouse cultured cerebellar Purkinje cells, as did deletion of the immediate
      early gene Arc. Using neuronal bacterial artificial chromosome (BAC)
      transfection, we found that, in Arc-/- cells transfected with a wild-type Arc
      BAC, late-phase LTD was rescued. However, mutation of one SRF-binding site in the
      Arc promoter (SRE 6.9) blocked this rescue. Co-transfection of wild-type Arc and
      SRF engineered to bind mutated SRE 6.9 restored late-phase LTD in Arc-/-, SRE 6.9
      mutant BAC cells. Thus, SRF binding to SRE 6.9 in the Arc promoter is required
      for the late phase of cerebellar LTD.

PMID- 20694005
TI  - Structural rearrangements of the ribosome at the tRNA proofreading step.
AB  - Discrimination of tRNA on the ribosome occurs in two consecutive steps: initial
      selection and proofreading. Here we propose a proofreading mechanism based on
      comparison of crystal structures of the 70S ribosome with an empty A site or with
      the A site occupied by uncharged cognate or near-cognate tRNA. We observe that
      ribosomal proteins S13, S19, L16, L25, L27 and L31 are actively involved in the
      proofreading of tRNA. We suggest that proofreading begins with the monitoring of
      the entire anticodon loop of tRNA by nucleotides from 16S rRNA (helices 18 and
      44) of the small subunit and 23S rRNA (helix 69) of the large subunit with
      involvement of magnesium ions. Subsequently, the elbow region is scanned by rRNA
      (helices 38 and 89) and proteins from the large subunit determining whether to
      accommodate the acceptor end of tRNA in the peptidyl transferase center or not.

PMID- 20694004
TI  - PTEN deletion enhances the regenerative ability of adult corticospinal neurons.
AB  - Despite the essential role of the corticospinal tract (CST) in controlling
      voluntary movements, successful regeneration of large numbers of injured CST
      axons beyond a spinal cord lesion has never been achieved. We found that
      PTEN/mTOR are critical for controlling the regenerative capacity of mouse
      corticospinal neurons. After development, the regrowth potential of CST axons was
      lost and this was accompanied by a downregulation of mTOR activity in
      corticospinal neurons. Axonal injury further diminished neuronal mTOR activity in
      these neurons. Forced upregulation of mTOR activity in corticospinal neurons by
      conditional deletion of Pten, a negative regulator of mTOR, enhanced compensatory
      sprouting of uninjured CST axons and enabled successful regeneration of a cohort
      of injured CST axons past a spinal cord lesion. Furthermore, these regenerating
      CST axons possessed the ability to reform synapses in spinal segments distal to
      the injury. Thus, modulating neuronal intrinsic PTEN/mTOR activity represents a
      potential therapeutic strategy for promoting axon regeneration and functional
      repair after adult spinal cord injury.

PMID- 20694006
TI  - Mycobacterium tuberculosis lipoprotein LprG (Rv1411c) binds triacylated
      glycolipid agonists of Toll-like receptor 2.
AB  - Knockout of lprG results in decreased virulence of Mycobacterium tuberculosis
      (MTB) in mice. MTB lipoprotein LprG has TLR2 agonist activity, which is thought
      to be dependent on its N-terminal triacylation. Unexpectedly, here we find that
      nonacylated LprG retains TLR2 activity. Moreover, we show LprG association with
      triacylated glycolipid TLR2 agonists lipoarabinomannan, lipomannan and
      phosphatidylinositol mannosides (which share core structures). Binding of
      triacylated species was specific to LprG (not LprA) and increased LprG TLR2
      agonist activity; conversely, association of glycolipids with LprG enhanced their
      recognition by TLR2. The crystal structure of LprG in complex with
      phosphatidylinositol mannoside revealed a hydrophobic pocket that accommodates
      the three alkyl chains of the ligand. In conclusion, we demonstrate a glycolipid
      binding function of LprG that enhances recognition of triacylated MTB glycolipids
      by TLR2 and may affect glycolipid assembly or transport for bacterial cell wall
      biogenesis.

PMID- 20694007
TI  - An overlapping kinase and phosphatase docking site regulates activity of the
      retinoblastoma protein.
AB  - The phosphorylation state and corresponding activity of the retinoblastoma tumor
      suppressor protein (Rb) are modulated by a balance of kinase and phosphatase
      activities. Here we characterize the association of Rb with the catalytic subunit
      of protein phosphatase 1 (PP1c). A crystal structure identifies an enzyme docking
      site in the Rb C-terminal domain that is required for efficient PP1c activity
      toward Rb. The phosphatase docking site overlaps with the known docking site for
      cyclin-dependent kinase (Cdk), and PP1 competition with Cdk-cyclins for Rb
      binding is sufficient to retain Rb activity and block cell-cycle advancement.
      These results provide the first detailed molecular insights into Rb activation
      and establish a novel mechanism for Rb regulation in which kinase and phosphatase
      compete for substrate docking.

PMID- 20694008
TI  - Double-stranded RNAs containing multiple IU pairs are sufficient to suppress
      interferon induction and apoptosis.
AB  - Adenosine deaminases acting on RNA (ADARs) catalyze hyperediting of long double
      stranded RNAs (dsRNAs), whereby up to 50% of adenosines are converted to inosine
      (I). Although hyperedited dsRNAs (IU-dsRNAs) have been implicated in various
      cellular functions, we now provide evidence for another role. We show that IU
      dsRNA suppresses the induction of interferon-stimulated genes (ISGs) and
      apoptosis by poly(IC). Moreover, we show that IU-dsRNA inhibits the activation of
      interferon regulatory factor 3 (IRF3), which is essential for the induction of
      ISGs and apoptosis. Finally, we speculate that the inhibition of IRF3 results
      from specific binding of IU-dsRNA to MDA-5 or RIG-I, both of which are cytosolic
      sensors for poly(IC). Although our data are consistent with a previous study in
      which ADAR1 deletion resulted in increased expression of ISGs and apoptosis, we
      show that IU-dsRNA per se suppresses ISGs and apoptosis. We therefore propose
      that any IU-dsRNA generated by ADAR1 can inhibit both pathways.

PMID- 20694009
TI  - Complement regulator CD46 temporally regulates cytokine production by
      conventional and unconventional T cells.
AB  - In this study we demonstrate a new form of immunoregulation: engagement on CD4(+)
      T cells of the complement regulator CD46 promoted the effector potential of T
      helper type 1 cells (T(H)1 cells), but as interleukin 2 (IL-2) accumulated, it
      switched cells toward a regulatory phenotype, attenuating IL-2 production via the
      transcriptional regulator ICER/CREM and upregulating IL-10 after interaction of
      the CD46 tail with the serine-threonine kinase SPAK. Activated CD4(+) T cells
      produced CD46 ligands, and blocking CD46 inhibited IL-10 production. Furthermore,
      CD4(+) T cells in rheumatoid arthritis failed to switch, consequently producing
      excessive interferon-gamma (IFN-gamma). Finally, gammadelta T cells, which rarely
      produce IL-10, expressed an alternative CD46 isoform and were unable to switch.
      Nonetheless, coengagement of T cell antigen receptor (TCR) gammadelta and CD46
      suppressed effector cytokine production, establishing that CD46 uses distinct
      mechanisms to regulate different T cell subsets during an immune response.

PMID- 20694010
TI  - The human cytomegalovirus microRNA miR-UL112 acts synergistically with a cellular
      microRNA to escape immune elimination.
AB  - Although approximately 200 viral microRNAs are known, only very few share similar
      targets with their host's microRNAs. A notable example of this is the stress
      induced ligand MICB, which is targeted by several distinct viral and cellular
      microRNAs. Through the investigation of the microRNA-mediated immune-evasion
      strategies of herpesviruses, we initially identified two new cellular microRNAs
      that targeted MICB and were expressed differently both in healthy tissues and
      during melanocyte transformation. We show that coexpression of various pairs of
      cellular microRNAs interfered with the downregulation of MICB, whereas the viral
      microRNAs optimized their targeting ability to efficiently downregulate MICB.
      Moreover, we demonstrate that through site proximity and possibly inhibition of
      translation, a human cytomegalovirus (HCMV) microRNA acts synergistically with a
      cellular microRNA to suppress MICB expression during HCMV infection.

PMID- 20694011
TI  - Association of IFIH1 and other autoimmunity risk alleles with selective IgA
      deficiency.
AB  - To understand the genetic predisposition to selective immunoglobulin A deficiency
      (IgAD), we performed a genome-wide association study in 430 affected individuals
      (cases) from Sweden and Iceland and 1,090 ethnically matched controls, and we
      performed replication studies in two independent European cohorts. In addition to
      the known association of HLA with IgAD, we identified association with a
      nonsynonymous variant in IFIH1 (rs1990760G>A, P = 7.3 x 10(-10)) which was
      previously associated with type 1 diabetes and systemic lupus erythematosus.
      Variants in CLEC16A, another known autoimmunity locus, showed suggestive evidence
      for association (rs6498142C>G, P = 1.8 x 10(-7)), and 29 additional loci were
      identified with P < 5 x 10(-5). A survey in IgAD of 118 validated non-HLA
      autoimmunity loci indicated a significant enrichment for association with
      autoimmunity loci as compared to non-autoimmunity loci (P = 9.0 x 10(-4)) or
      random SNPs across the genome (P < 0.0001). These findings support the hypothesis
      that autoimmune mechanisms may contribute to the pathogenesis of IgAD.

PMID- 20694012
TI  - Germline CBL mutations cause developmental abnormalities and predispose to
      juvenile myelomonocytic leukemia.
AB  - CBL encodes a member of the Cbl family of proteins, which functions as an E3
      ubiquitin ligase. We describe a dominant developmental disorder resulting from
      germline missense CBL mutations, which is characterized by impaired growth,
      developmental delay, cryptorchidism and a predisposition to juvenile
      myelomonocytic leukemia (JMML). Some individuals experienced spontaneous
      regression of their JMML but developed vasculitis later in life. Importantly,
      JMML specimens from affected children show loss of the normal CBL allele through
      acquired isodisomy. Consistent with these genetic data, the common p.371Y>H
      altered Cbl protein induces cytokine-independent growth and constitutive
      phosphorylation of ERK, AKT and S6 only in hematopoietic cells in which normal
      Cbl expression is reduced by RNA interference. We conclude that germline CBL
      mutations have developmental, tumorigenic and functional consequences that
      resemble disorders that are caused by hyperactive Ras/Raf/MEK/ERK signaling and
      include neurofibromatosis type 1, Noonan syndrome, Costello syndrome,
      cardiofaciocutaneous syndrome and Legius syndrome.

PMID- 20694013
TI  - Genome-wide association study identifies variants in the CFH region associated
      with host susceptibility to meningococcal disease.
AB  - Meningococcal disease is an infection caused by Neisseria meningitidis. Genetic
      factors contribute to host susceptibility and progression to disease, but the
      genes responsible for disease development are largely unknown. We report here a
      genome-wide association study for host susceptibility to meningococcal disease
      using 475 individuals with meningococcal disease (cases) and 4,703 population
      controls from the UK. We performed, in Western European and South European
      cohorts (consisting of 968 cases and 1,376 controls), two replication studies for
      the most significant SNPs. A cluster of complement factor SNPs replicated
      independently in both cohorts, including SNPs within complement factor H (CFH)
      (rs1065489 (p.936D<E), P = 2.2 x 10(-11)) and in CFH-related protein 3
      (CFHR3)(rs426736, P = 4.6 x 10(-13)). N. meningitidis is known to evade
      complement-mediated killing by the binding of host CFH to the meningococcal
      factor H-binding protein (fHbp). Our study suggests that host genetic variation
      in these regulators of complement activation plays a role in determining the
      occurrence of invasive disease versus asymptomatic colonization by this pathogen.

PMID- 20694014
TI  - Genome-wide association analyses identifies a susceptibility locus for
      tuberculosis on chromosome 18q11.2.
AB  - We combined two tuberculosis genome-wide association studies from Ghana and The
      Gambia with subsequent replication in a combined 11,425 individuals. rs4331426,
      located in a gene-poor region on chromosome 18q11.2, was associated with disease
      (combined P = 6.8 x 10(-9), odds ratio = 1.19, 95% CI = 1.13-1.27). Our study
      demonstrates that genome-wide association studies can identify new susceptibility
      loci for infectious diseases, even in African populations, in which levels of
      linkage disequilibrium are particularly low.

PMID- 20694017
TI  - Inhibitory actions of mibefradil on steroidogenesis in mouse Leydig cells:
      involvement of Ca(2+) entry via the T-type Ca(2+) channel.
AB  - Intracellular cAMP and Ca(2+) are involved in the regulation of steroidogenic
      activity in Leydig cells, which coordinate responses to luteinizing hormone (LH)
      and human chorionic gonadotropin (hCG). However, the identification of Ca(2+)
      entry implicated in Leydig cell steroidogenesis is not well defined. The
      objective of this study was to identify the type of Ca(2+) channel that affects
      Leydig cell steroidogenesis. In vitro steroidogenesis in the freshly dissociated
      Leydig cells of mice was induced by hCG incubation. The effects of mibefradil (a
      putative T-type Ca(2+) channel blocker) on steroidogenesis were assessed using
      reverse transcription (RT)-polymerase chain reaction analysis for the
      steroidogenic acute regulatory protein (StAR) mRNA expression and testosterone
      production using radioimmunoassay. In the presence of 1.0 mmol L(-1)
      extracellular Ca(2+), hCG at 1 to 100 IU noticeably elevated both StAR mRNA level
      and testosterone secretion (P < 0.05), and the stimulatory effects of hCG were
      markedly diminished by mibefradil in a dose-dependent manner (P < 0.05).
      Moreover, the hCG-induced increase in testosterone production was completely
      removed when external Ca(2+) was omitted, implying that Ca(2+) entry is needed
      for hCG-induced steroidogenesis. Furthermore, a patch-clamp study revealed the
      presence of mibefradil-sensitive Ca(2+) currents seen at a concentration range
      that nearly paralleled those inhibiting steroidogenesis. Collectively, our data
      provide evidence that hCG-stimulated steroidogenesis is mediated at least in part
      by Ca(2+) entry carried out by the T-type Ca(2+) channel in the Leydig cells of
      mice.

PMID- 20694018
TI  - Efficacy of maximal androgen blockade versus castration alone in the treatment of
      advanced prostate cancer: a retrospective clinical experience from a Chinese
      medical centre.
AB  - In this retrospective study, we evaluated and compared the efficacy and
      toxicities of maximal androgen blockade (MAB) versus castration alone in Chinese
      patients with advanced prostate cancer. From 1996 to 2004, 608 patients with
      advanced prostate cancer were included in the study. Patients were
      retrospectively divided into two groups according to different therapeutic
      regimens. Of the 608 patients, 300 patients were treated with MAB (castration
      plus nonsteroidal antiandrogens) and the remaining 308 were treated with
      castration alone. The 2- and 5-year overall survival rates of these patients were
      73.7% and 56%, respectively. Multivariate analysis showed that, in patients with
      metastatic prostate cancer, MAB was associated with not only the improvement of
      progression-free survival (PFS) (increased by 10 months) but also a 20.6%
      reduction in mortality risk compared with castration alone. In contrast, the
      efficacy of MAB was not superior to castration alone for patients with
      nonmetastatic prostate cancer. Interestingly, among patients with MAB, those
      using bicalutamide had a longer PFS than those using flutamide; this was
      especially so in patients with metastatic prostate cancer. Almost all of the
      toxicities due to the hormone therapy were mild to moderate and manageable. To
      conclude, in China, hormone therapies, including MAB and castration alone, have
      been standard treatments for advanced prostate cancer. For patients with
      nonmetastatic prostate cancer, castration alone might be adequately practical and
      efficient. In patients with metastatic prostate cancer, however, MAB has superior
      efficacy over castration alone. It is clear that MAB should be considered the
      first-line standard treatment for patients with metastatic prostate cancer.

PMID- 20694019
TI  - Protein tyrosine phosphorylation of the human sperm head during capacitation:
      immunolocalization and relationship with acquisition of sperm-fertilizing
      ability.
AB  - The occurrence of tyrosine phosphorylation (TP) in the sperm head during
      capacitation has been poorly investigated, and no data exist on the relationship
      of its dynamics with the acquisition of sperm fertilizing ability. This study
      localized TP of head proteins in human spermatozoa during capacitation and
      explored its relationship with acquisition of the ability to display progesterone
      (P)-stimulated acrosome reactions (ARs) and to penetrate zona-free hamster
      oocytes. By immunofluorescence, TP immunoreactivity was revealed in the acrosomal
      region of formaldehyde-fixed/unpermeabilized samples, whereas it was abolished in
      fixed/permeabilized samples, in which TP immunoreactivity was high in the
      principal piece. No TP immunoreactivity was detectable in unfixed spermatozoa.
      Head TP immunoreactivity was localized externally to the acrosome, close to the
      cytoplasmic membrane, as assessed by transmission electron microscopy. The
      increase in head TP was an early event during capacitation, occurring within 1 h
      in capacitating conditions. At this time, the P-stimulated ARs were also
      increased, whereas egg penetration was as poor as in uncapacitated spermatozoa.
      At 5 h of capacitation, the extent of neither head TP nor the P-induced ARs were
      greater than that at 1 h, whereas egg penetration had significantly increased.
      Seminal plasma inhibited head TP, P-induced ARs and egg penetration. None of
      these inhibitory effects, unlike those on tail TP, were prevented by the cAMP
      analogue dbcAMP (N,2-O-dibutyryladenosine 3',5'-cyclic monophosphate). In
      conclusion, head TP is a subsurface event occurring early during capacitation and
      is closely related to acquisition of the ability to display P-stimulated ARs,
      whereas the ability to fuse with oolemma and to decondense is a later
      capacitation-related event.

PMID- 20694020
TI  - Type I natural killer T cells: naturally born for fighting.
AB  - Type capital I, Ukrainian natural killer T cells (NKT cells), a subset of CD1d
      restricted T cells with invariant Valphabeta TCR, are characterized by prompt
      production of large amounts of Th1 and/or Th2 cytokines upon primary stimulation
      through the TCR complex. The rapid release of cytokines implies that type capital
      I, Ukrainian NKT cells may play a critical role in modulating the upcoming immune
      responses, such as anti-tumor response, protection against infection, and
      autoimmunity. As a bridge between innate and adaptive immunity, type capital I,
      Ukrainian NKT cells differentiate and mature upon stimulations to achieve and
      maintain a homeostasis. Orchestrating with other arms of adaptive immunity, type
      capital I, Ukrainian NKT cells show strong cytotoxic effects in response to
      various tumors in a direct and/or indirect manner(s). This review will focus
      primarily on type capital I, Ukrainian NKT cell development, homeostasis, and
      effector functions, especially in anti-tumor immunity, and followed by their
      potential applications in treatment of cancers.

PMID- 20694021
TI  - Research and development of next generation of antibody-based therapeutics.
AB  - Monoclonal antibodies (mAb) are emerging as one of the major class of therapeutic
      agents in the treatment of many human diseases, in particular in cancer and
      immunological disorders. To date, 28 mAb have been approved by the United States
      Food and Drug Administration for clinical applications. In addition, several
      hundreds of mAb are being developed clinically by many biotech and pharmaceutical
      companies for various disease indications. Many challenges still remain, however,
      and the full potential of therapeutic antibodies has yet to be realized. With the
      advancement of antibody engineering technologies and our further understanding of
      disease biology as well as antibody mechanism of action, many classes of novel
      antibody formats or antibody derived molecules are emerging as promising new
      generation therapeutics. These new antibody formats or molecules are carefully
      designed and engineered to acquire special features, such as improved
      pharmacokinetics, increased selectivity, and enhanced efficacy. These new agents
      may have the potential to revolutionize both our thinking and practice in the
      efforts to research and develop next generation antibody-based therapeutics.

PMID- 20694023
TI  - Emerging role of junctophilin-2 as a regulator of calcium handling in the heart.
AB  - Junctophilin-2 (JPH2) is a membrane-binding protein that plays a key role in the
      organization of the junctional membrane complex (JMC) in cardiac myocytes. JPH2
      is believed to keep the plasma membrane and sarcoplasmic reticulum at a fixed
      distance within the JMC, which is essential for proper Ca(2+)-induced Ca(2+)
      release during the excitation-contraction process. Recent studies have revealed
      that mutations in the JPH2 gene are associated with hypertrophic cardiomyopathy,
      highlighting the importance of this protein for normal cardiac physiology. In
      this paper, we review current knowledge about the structure and function of
      junctophilin-2 in the heart.

PMID- 20694022
TI  - Autophagic pathways as new targets for cancer drug development.
AB  - Autophagy is an evolutionarily conserved lysosomal self-digestion process
      involved in degradation of long-lived proteins and damaged organelles. In recent
      years, increasing evidence indicates that autophagy is associated with a number
      of pathological processes, including cancer. In this review, we focus on the
      recent studies of the evolutionarily conserved autophagy-related genes (ATGs)
      that are implicated in autophagosome formation and the pathways involved. We
      discuss several key autophagic mediators (eg, Beclin-1, UVRAG, Bcl-2, Class III
      and I PI3K, mTOR, and p53) that play pivotal roles in autophagic signaling
      networks in cancer. We discuss the Janus roles of autophagy in cancer and
      highlighted their relationship to tumor suppression and tumor progression. We
      also present some examples of targeting ATGs and several protein kinases as
      anticancer strategy, and discuss some autophagy-modulating agents as antitumor
      agents. A better understanding of the relationship between autophagy and cancer
      would ultimately allow us to harness autophagic pathways as new targets for drug
      discovery in cancer therapeutics.

PMID- 20694024
TI  - Recent advances in (patho)physiology of astroglia.
AB  - Our view of astrocytes in the operation of the brain is changing dramatically
      over the last 3 decades. Astroglial calcium excitability controls the release of
      gliotransmitters, which can occur at the tripartite synapse. Astrocytes not only
      modulate synaptic transmission by releasing and taking up transmitters, but also
      receiving neuronal signals that act upon astrocytic plasma membrane receptors.
      This process represents the bidirectional neurone-glia communication.
      Additionally, astrocytes play role in the regulation of blood flow as well as ion
      and water homeostasis. Many of the brain dysfunctions are primary astropathies,
      including hepatic encephalopathy and Alexander disease, while other brain
      malfunctions, such as epilepsy and Alzheimer disease, may have substantial
      astrocytic contribution. Thus, these star-shaped cells by their roles in
      (patho)physiology of the brain seem to live up to the expectation one can have
      from their given name - astrocyte.

PMID- 20694025
TI  - Potential therapeutics specific to c-MET/RON receptor tyrosine kinases for
      molecular targeting in cancer therapy.
AB  - Products of proto-oncogenes c-MET and RON belong to a subfamily of receptor
      tyrosine kinases that contribute significantly to tumorigenic progression. In
      primary tumors, altered c-MET/RON expression transduces signals regulating
      invasive growth that is characterized by cell migration and matrix invasion.
      These pathogenic features provide the basis for targeting c-MET/RON in cancer
      therapy. In the last decade, various approaches have been investigated to
      suppress c-MET/RON-transduced oncogenesis. Among the therapeutics developed,
      monoclonal antibodies (mAbs) and small-molecule inhibitors (SMIs) have emerged as
      promising candidates. The mechanism of these therapeutic candidates is the
      disruption of tumor dependency on c-MET/RON signals for survival. The mAbs
      specific to hepatocyte growth factor (AMG102) and c-MET (MetMAb) are both
      humanized and able to block c-MET signaling, leading to inhibition of tumor cell
      proliferation in vitro and inhibition of tumor growth in xenograft models. The
      mAb AMG102 neutralizes hepatocyte growth factor and enhances the cytotoxicity of
      various chemotherapeutics to tumors in vivo. AMG102 is currently in phase II
      clinical trials for patients with advanced solid tumors. IMC-41A40 and Zt/f2 are
      RON-specific mAbs that down-regulate RON expression and inhibit ligand-induced
      phosphorylation. Both mAbs inhibit tumor growth in mice mediated by colon and
      pancreatic cancer cells. SMIs specific to c-MET (ARQ107 and PF-02341066) are in
      various phases of clinical trials. Therapeutic efficacy has also been observed
      with dual inhibitors such as Compound I, which is specific to c-MET/RON. However,
      a potential issue is the emergence of acquired resistance to these inhibitors.
      Clearly, development of c-MET/RON therapeutics provides opportunities and
      challenges for combating cancer in the future.

PMID- 20694028
TI  - The Role of Ethnicity in Father Absence and Children's School Enrollment in
      Guatemala.
AB  - Despite the historical prevalence of single motherhood in Latin America and its
      rise in recent years, there is limited knowledge on the magnitude and
      consequences of father absence as experienced by children. Using a nationally
      representative sample from the 2002 Guatemalan Reproductive Health Survey, this
      study provides unprecedented documentation on the national prevalence of
      children's separate living arrangements from their biological fathers and
      nonresident fathers' paternity establishment and child support payments. Using
      random-intercept models, this study further demonstrates that father absence has
      a negative effect on the school enrollment of indigenous children of both sexes
      and Ladino male children. Increased poverty in father-absent households explains
      a smaller proportion of this adverse effect on indigenous children, suggesting
      that their fathers, when present, play a stronger social, rather than economic,
      role compared to their Ladino counterparts. Finally, child support payments
      attenuate the negative effects of father absence, particularly among Ladino male
      children.

PMID- 20694029
TI  - Ethnicity at the Individual and Neighborhood Level as an Explanation for Moving
      Out of the Neighborhood.
AB  - We address the influence of both the ethnic composition of the neighborhood and
      the ethnicity of individual residents on moving out of neighborhoods in the
      Netherlands. Using the Housing Research Netherlands survey and multinomial
      logistic regression analyses of moving out versus not moving or moving within the
      neighborhood, we found that ethnicity at the individual level was not of much
      importance for moving out. The combination of ethnicity at the individual level
      and the neighborhood level, however, appeared to be a rather important
      explanation of geographical mobility. Ethnic minorities are more likely than
      native Dutch to move within neighborhoods, and less likely to move away from
      them, as the share of non-western minorities in those neighborhoods increases.
      Native Dutch move away more frequently than ethnic minorities as the share of non
      western ethnic minorities in neighborhoods is greater. These results suggest
      ethnic enclave formation or place stratification in the Netherlands.

PMID- 20694026
TI  - A field guide to bacterial swarming motility.
AB  - How bacteria regulate, assemble and rotate flagella to swim in liquid media is
      reasonably well understood. Much less is known about how some bacteria use
      flagella to move over the tops of solid surfaces in a form of movement called
      swarming. The focus of bacteriology is changing from planktonic to surface
      environments, and so interest in swarming motility is on the rise. Here, I review
      the requirements that define swarming motility in diverse bacterial model
      systems, including an increase in the number of flagella per cell, the secretion
      of a surfactant to reduce surface tension and allow spreading, and movement in
      multicellular groups rather than as individuals.

PMID- 20694027
TI  - The role of secretory antibodies in infection immunity.
AB  - The mucosal secretory immune system provides an important primary defence against
      disease, as studies of humans with mucosal humoral immunodeficiencies suggest
      that the absence of secretory immunoglobulin A leads to an increase in mucosal
      infections. However, the infection risks posed do not seem to provide the
      evolutionary drive to retain constitutive secretion of often 'hard won' protein,
      suggesting that secretory antibodies may have some other important function (or
      functions). This Review examines the evidence that secretory antibodies provide
      an important defence against infection in specific animal models and explores
      complementary explanations for the evolution of the secretory immune system.

PMID- 20694030
TI  - Demography and Public Health Emergency Preparedness: Making the Connection.
AB  - THE TOOLS AND TECHNIQUES OF POPULATION SCIENCES ARE EXTREMELY RELEVANT TO THE
      DISCIPLINE OF PUBLIC HEALTH EMERGENCY PREPAREDNESS: protecting and securing the
      population's health requires information about that population. While related
      fields such as security studies have successfully integrated demographic tools
      into their research and literature, the theoretical and practical connection
      between the methods of demography and the practice of public health emergency
      preparedness is weak. This article suggests the need to further the
      interdisciplinary use of demography by examining the need for a systematic use of
      population science techniques in public health emergency preparedness.
      Ultimately, we demonstrate how public health emergency preparedness can
      incorporate demography to develop more effective preparedness plans. Important
      policy implications emerge: demographers and preparedness experts need to
      collaborate more formally in order to facilitate community resilience and
      mitigate the consequences of public health emergencies.

PMID- 20694031
TI  - The Context of Current Content Analysis of Gender Roles: An Introduction to a
      Special Issue.
AB  - The aim of this paper is to provide context for the quantitative content analyses
      of gender roles that are to be included in both parts of this special issue.
      First, a timeline of historical uses of the content analysis methodology is
      presented. Second, research objectives that frequently drive content analysis of
      gender roles are described; these include: to support feminist claims, to compare
      media with real life, to predict effects on audiences, and to detect effects of
      media producers on content. Third, previous content analyses published in Sex
      Roles and other gender-focused journals are reviewed and categorized in terms of
      medium, genre, time span, gender, and nationality. Finally, contributions of each
      of the articles in this special issue are outlined.

PMID- 20694032
TI  - Factors associated with hernia and bulge formation at the donor site of the
      pedicled TRAM flap.
AB  - The purpose of this study was to evaluate the correlation between risk factors
      and hernia or bulge formation at the donor site of the transverse rectus
      abdominis myocutaneous (TRAM) flap. A retrospective study was conducted between
      September 2005 and December 2008 in 206 patients who underwent breast
      reconstruction with pedicled TRAM flap. Eight (3.9%) of these patients had
      abdominal wall hernia and 26 (12.6%) had abdominal bulging. The incidence of
      hernia was significantly higher (P < 0.05) among patients with body mass index
      (BMI) >/= 30 kg/m(2) (hernia incidence, 15.0%) than that among patients with BMI
      <30 kg/m(2) (hernia incidence, 3.2%), while the incidence of abdominal bulge was
      significantly lower (P < 0.05) among patients with BMI >/= 30 kg/m(2) (abdominal
      bulge incidence, 5.0%) than that among patients with BMI >/= 30 kg/m(2)
      (abdominal bulge incidence, 19.1%). Therefore, obesity was identified as a risk
      factor for abdominal wall hernia. It was also found that the use of mesh to
      reinforce the abdominal wall significantly reduced (P < 0.025) the incidence of
      hernia (use of mesh (hernia incidence, 2.5%) versus non-mesh (hernia incidence,
      5.9%)) and abdominal bulge (use of mesh (abdominal bulge incidence, 9.9%) versus
      non-mesh (abdominal bulge incidence, 17.3%)) among the patients.

PMID- 20694033
TI  - Early outcome of facial reconstructive surgery abroad: a comparative study.
AB  - Every year, many medical missions are undertaken in the developing world but
      there is almost a universal lack of outcome data on the quality of these
      missions. The present study compares early clinical outcome and complication rate
      in two consecutive missions (facial reconstruction) undertaken to Ethiopia in
      2007 and 2008. The object was to establish if measures adopted following feedback
      from the first mission led to improvement of the results. A significant
      improvement was observed in early clinical outcome and there were less severe
      complications in the 2008 compared to the 2007 mission. On both occasions,
      significantly more complications were experienced after complex compared to
      simple procedures. Despite improved outcome in 2008, 50% of the complex cases had
      an unfavourable clinical result. The data suggest that early outcome studies are
      a useful method of critically evaluating the quality of surgical mission. The
      unsatisfactory outcome of complex procedures underlines the need for feedback on
      the quality of these missions.

PMID- 20694034
TI  - Evidence-Based Mental Health Programs in Schools: Barriers and Facilitators of
      Successful Implementation.
AB  - Although schools can improve children's access to mental health services, not all
      school-based providers are able to successfully deliver evidence-based practices.
      Indeed, even when school clinicians are trained in evidence-based practices
      (EBP), the training does not necessarily result in the implementation of those
      practices. This study explores factors that influence implementation of a
      particular EBP, Cognitive Behavioral Intervention for Trauma in Schools (CBITS).
      Semi-structured telephone interviews with 35 site administrators and clinicians
      from across the United States were conducted 6-18 months after receiving CBITS
      training to discuss implementation experiences. The implementation experiences of
      participants differed, but all reported similar barriers to implementation. Sites
      that successfully overcame such barriers differed from their unsuccessful
      counterparts by having greater organizational structure for delivering school
      services, a social network of other clinicians implementing CBITS, and
      administrative support for implementation. This study suggests that EBP
      implementation can be facilitated by having the necessary support from school
      leadership and peers.

PMID- 20694035
TI  - Association mapping of spot blotch resistance in wild barley.
AB  - Spot blotch, caused by Cochliobolus sativus, is an important foliar disease of
      barley. The disease has been controlled for over 40 years through the deployment
      of cultivars with durable resistance derived from the line NDB112. Pathotypes of
      C. sativus with virulence for the NDB112 resistance have been detected in Canada;
      thus, many commercial cultivars are vulnerable to spot blotch epidemics. To
      increase the diversity of spot blotch resistance in cultivated barley, we
      evaluated 318 diverse wild barley accessions comprising the Wild Barley Diversity
      Collection (WBDC) for reaction to C. sativus at the seedling stage and utilized
      an association mapping (AM) approach to identify and map resistance loci. A high
      frequency of resistance was found in the WBDC as 95% (302/318) of the accessions
      exhibited low infection responses. The WBDC was genotyped with 558 Diversity
      Array Technology (DArT((R))) and 2,878 single nucleotide polymorphism (SNP)
      markers and subjected to structure analysis before running the AM procedure.
      Thirteen QTL for spot blotch resistance were identified with DArT and SNP
      markers. These QTL were found on chromosomes 1H, 2H, 3H, 5H, and 7H and explained
      from 2.3 to 3.9% of the phenotypic variance. Nearly half of the identified QTL
      mapped to chromosome bins where spot blotch resistance loci were previously
      reported, offering some validation for the AM approach. The other QTL mapped to
      unique genomic regions and may represent new spot blotch resistance loci. This
      study demonstrates that AM is an effective technique for identifying and mapping
      QTL for disease resistance in a wild crop progenitor. ELECTRONIC SUPPLEMENTARY
      MATERIAL: The online version of this article (doi:10.1007/s11032-010-9402-8)
      contains supplementary material, which is available to authorized users.

PMID- 20694036
TI  - The Role of Rumination and Reduced Concreteness in the Maintenance of
      Posttraumatic Stress Disorder and Depression Following Trauma.
AB  - Rumination has been linked to posttraumatic stress disorder (PTSD) and depression
      following trauma. A cross-sectional (N = 101) and a prospective longitudinal
      study (N = 147) of road traffic accident survivors assessed rumination, PTSD and
      depression with self-report measures and structured interviews. We tested the
      hypotheses that (1) rumination predicts the maintenance of PTSD and depression
      and (2) reduced concreteness of ruminative thinking may be a maintaining factor.
      Rumination significantly predicted PTSD and depression at 6 months over and above
      what could be predicted from initial symptom levels. In contrast to the second
      hypothesis, reduced concreteness in an iterative rumination task was not
      significantly correlated with self-reported rumination frequency, and did not
      consistently correlate with symptom severity measures. However, multiple
      regression analyses showed that the combination of reduced concreteness and self
      reported frequency of rumination predicted subsequent PTSD better than rumination
      frequency alone. The results support the view that rumination is an important
      maintaining factor of trauma-related emotional disorders.

PMID- 20694037
TI  - Apolipoprotein E Genotype and Cardiovascular Diseases in the Elderly.
AB  - The apolipoprotein E (APOE) genotype is a genetic risk factor for dementia,
      Alzheimer's disease, and cardiovascular disease (CVD). It includes three alleles
      (e2, e3, e4) that are located on chromosome 19q3.2. The e3 allele is the most
      common and is more common in people of Northern European ancestry and less common
      in those of Asian ancestry. Those with at least one e4 allele are at increased
      risk for CVD outcomes. It is well established that the presence of an e4 allele
      is linked to higher low-density lipoprotein cholesterol levels, even at young
      ages. Even though most CVD occurs in older people, there are few studies of the
      effects of APOE on CVD in older people. This review addresses recent research on
      the links between APOE, CVD, and vascular mechanisms by which APOE may affect CVD
      in the elderly.

PMID- 20694038
TI  - Assessment of Relapse Following Intraoral Vertical Ramus Osteotomy Mandibular
      Setback and Short-term Immobilization.
AB  - AIM: Relapse is an important issue of concern following operations for mandibular
      setback. Decreasing the immobilization (IMF) period may play a role in this
      regard. Usual IMF period ranges from 1 to 2 months. We aimed to assess relapse
      following a 1-week IMF period. MATERIALS AND METHODS: This study aimed to assess
      40 purely prognathic patients who had undergone Vertical Ramus osteotomy for
      mandibular setback. After the release of IMF, guiding elastics were used to
      direct the mandible to maximal intercuspation for 3 weeks. Relapse was measured
      from cephalometric radiographs preoperatively and 1 year postoperatively.
      RESULTS: The mean skeletal horizontal relapse after 1 year in 40 treated patients
      was 0.6 mm. CONCLUSION: The mean skeletal horizontal relapse after 1 year was
      similar to figures reported for this operation with longer fixation.

PMID- 20694039
TI  - Religion and Self: Notions from a Cultural Psychological Perspective.
AB  - After a brief introduction of a cultural psychological perspective, this paper
      turns to the concept of self. The paper proposes to conceive of that reality to
      which the concepts of self refer as a narrative, employing especially
      autobiographies and other ego-documents in empirical exploration. After
      discussing some psychological theories about "self," the paper points out that
      they may well be applied in research on personal religiosity.

PMID- 20694040
TI  - Random Partition Models with Regression on Covariates.
AB  - Many recent applications of nonparametric Bayesian inference use random partition
      models, i.e. probability models for clustering a set of experimental units. We
      review the popular basic constructions. We then focus on an interesting extension
      of such models. In many applications covariates are available that could be used
      to a priori inform the clustering. This leads to random clustering models indexed
      by covariates, i.e., regression models with the outcome being a partition of the
      experimental units. We discuss some alternative approaches that have been used in
      the recent literature to implement such models, with an emphasis on a recently
      proposed extension of product partition models. Several of the reviewed
      approaches were not originally intended as covariate-based random partition
      models, but can be used for such inference.

PMID- 20694041
TI  - Quantitative Study of Rigid-Body and Respiratory Motion of Patients Undergoing
      Stress and Rest Cardiac SPECT Imaging.
AB  - We report patient motion in 110 Tl-201 cardiac perfusion SPECT studies in 66
      patients. The imaging consisted of emission followed by sequential transmission
      imaging during which motion tracking with a visual tracking system (VTS) was
      performed. We investigated the extent, time, and frequency of respiratory and
      rigid-body motion in these patients. We also determined whether the motion
      occurred gradually or in sudden jumps, whether it was sustained, and if it
      occurred along one or more axes predominantly. We then studied the differences in
      respiratory and body motion (BM), if any, between stress versus rest imaging
      groups, male versus female subjects, and exercise versus pharmacological stress
      groups. We found that 23% of the studies had sustained motion (> 4min.) of
      between 3-6 mm, and 5% had sustained motion larger than 6 mm during emission
      imaging. In terms of respiratory motion, 13% showed a downward trend of the
      respiratory baseline of more than 6 mm during emission imaging. Also, in 9% of
      the studies, the average position of patients was displaced by more than 3 mm
      between emission and transmission imaging phases. Both of these motions may lead
      to misalignment of the attenuation map. In hypothesis testing of grouped studies,
      it was determined that stress and rest imaging did not show any significant
      differences in body motion but did in respiratory motion associated with a change
      in respiration following stress. Exercise-stress studies showed a larger extent
      of respiratory motion than the pharmacologically induced stress studies.
      Significant differences in body and respiratory motion of male and female groups
      were also observed. A visual assessment of the reconstructed slices in the
      studies with measured motion was made to investigate the impact of the motion.
      Illustrative example studies are included.

PMID- 20694042
TI  - Bioorthogonal Chemistry-A Covalent Strategy for the Study of Biological Systems.

PMID- 20694043
TI  - A Bayesian Discovery Procedure.
AB  - We discuss a Bayesian discovery procedure for multiple comparison problems. We
      show that under a coherent decision theoretic framework, a loss function
      combining true positive and false positive counts leads to a decision rule based
      on a threshold of the posterior probability of the alternative. Under a semi
      parametric model for the data, we show that the Bayes rule can be approximated by
      the optimal discovery procedure (ODP), recently introduced by Storey (2007a).
      Improving the approximation leads us to a Bayesian discovery procedure (BDP),
      which exploits the multiple shrinkage in clusters implied by the assumed
      nonparametric model. We compare the BDP and the ODP estimates in a simple
      simulation study and in an assessment of differential gene expression based on
      microarray data from tumor samples. We extend the setting of the ODP by
      discussing modifications of the loss function that lead to different single
      thresholding statistics. Finally, we provide an application of the previous
      arguments to dependent (spatial) data.

PMID- 20694044
TI  - Olfactory experience affects the response of meadow voles to the opposite-sex
      scent donor of mixed-sex over-marks.
AB  - Scent marking and over-marking are important forms of communication between the
      sexes for many terrestrial mammals. Over the course of three experiments, we
      determined whether the amount of time individuals investigate the scent marks of
      opposite-sex conspecifics is affected by four days of olfactory experience with
      those conspecifics. In experiment 1, female meadow voles, Microtus
      pennsylvanicus, spent more time investigating the scent mark of the novel male
      conspecific than that of the familiar male donor, whereas male voles spent
      similar amounts of time investigating the scent mark of the familiar female and a
      novel female conspecific. In experiment 2, voles were exposed to a mixed-sex over
      mark in which subjects did not have four days of olfactory experience with either
      the top-scent donor or the bottom-scent donor. During the test phase, male and
      female voles spent more time investigating the scent mark of the opposite-sex
      conspecific that provided the top-scent mark than that of a novel, opposite-sex
      conspecific. Male and female voles spent similar amounts of time investigating
      the scent mark of the bottom-scent donor and that of a novel opposite-sex
      conspecific. In experiment 3, voles were exposed to a mixed-sex over-mark that
      contained the scent mark of an opposite-sex conspecific with which they had four
      days of olfactory experience. During the test phase, male voles spent more time
      investigating the mark of the familiar, top-scent female than the scent mark of a
      novel female donor but spent similar amounts of time investigating the mark of
      the familiar, bottom-scent female and that of a novel female donor. In contrast,
      female voles spent more time investigating the mark of a novel male donor than
      that of either the familiar, top-scent male or that of the familiar, bottom-scent
      male. The sex differences in the responses of voles to scent marks and mixed-sex
      over-marks are discussed in relation to the natural history and non-monogamous
      mating system of meadow voles.

PMID- 20694045
TI  - A Pairwise Preferential Interaction Model for Understanding Peptide Aggregation.
AB  - A pairwise preferential interaction model (PPIM), based on Kirkwood-Buff
      integrals, is developed to quantify and characterize the interactions between
      some of the functional groups commonly observed in peptides. The existing
      experimental data are analyzed to determine the preferential interaction (PI)
      parameters for different amino acid and small peptide systems in aqueous
      solutions. The PIs between the different functional groups present in the
      peptides are then isolated and quantified by assuming simple pairwise additivity.
      The PPIM approach provides consistent estimates for the pair interactions between
      the same functional groups obtained from different solute molecules. Furthermore,
      these interactions appear to be chemically intuitive. It is argued that this type
      of approach can provide valuable information concerning specific functional group
      correlations which could give rise to peptide aggregation.

PMID- 20694046
TI  - Quantification of Self Pollution from Two Diesel School Buses using Three
      Independent Methods.
AB  - We monitored two Seattle school buses to quantify the buses' self pollution using
      the dual tracers (DT), lead vehicle (LV), and chemical mass balance (CMB)
      methods. Each bus drove along a residential route simulating stops, with windows
      closed or open. Particulate matter (PM) and its constituents were monitored in
      the bus and from a LV. We collected source samples from the tailpipe and
      crankcase emissions using an on-board dilution tunnel. Concentrations of PM(1),
      ultrafine particle counts, elemental and organic carbon (EC/OC) were higher on
      the bus than the LV. The DT method estimated that the tailpipe and the crankcase
      emissions contributed 1.1 and 6.8 mug/m(3) of PM(2.5) inside the bus,
      respectively, with significantly higher crankcase self pollution (SP) when
      windows were closed. Approximately two-thirds of in-cabin PM(2.5) originated from
      background sources. Using the LV approach, SP estimates from the EC and the
      active personal DataRAM (pDR) measurements correlated well with the DT estimates
      for tailpipe and crankcase emissions, respectively, although both measurements
      need further calibration for accurate quantification. CMB results overestimated
      SP from the DT method but confirmed crankcase emissions as the major SP source.
      We confirmed buses' SP using three independent methods and quantified crankcase
      emissions as the dominant contributor.

PMID- 20694047
TI  - Health Insurance and the Labor Supply Decisions of Older Workers: Evidence from a
      U.S. Department of Veterans Affairs Expansion.
AB  - This paper exploits a major mid-1990s expansion in the U.S. Department of
      Veterans Affairs health care system to provide evidence on the labor market
      effects of expanding health insurance availability. Using data from the Current
      Population Survey, we employ a difference-in-differences strategy to compare the
      labor market behavior of older veterans and non-veterans before and after the VA
      health benefits expansion to test the impact of public health insurance on labor
      supply. We find that older workers are significantly more likely to decrease work
      both on the extensive and intensive margins after receiving access to non
      employer based insurance. Workers with some college education or a college degree
      are more likely to transition into self-employment, a result consistent with "job
      lock" effects. However, less-educated workers are more likely to leave self
      employment, a result suggesting that the positive income effect from receiving
      public insurance dominates the "job-lock" effect for these workers. Some
      relatively disadvantaged sub-populations may also increase their labor supply
      after gaining greater access to public insurance, consistent with complementary
      positive health effects of health care access or decreased work disincentives for
      these groups. We conclude that this reform has affected employment and retirement
      decisions, and suggest that future moves toward universal coverage or expansions
      of Medicare are likely to have significant labor market effects.

PMID- 20694048
TI  - FORMING SELF-ASSEMBLED CELL ARRAYS AND MEASURING THE OXYGEN CONSUMPTION RATE OF A
      SINGLE LIVE CELL.
AB  - We report a method for forming arrays of live single cells on a chip using
      polymer micro-traps made of SU8. We have studied the toxicity of the
      microfabricated structures and the associated environment for two cell lines. We
      also report a method for measuring the oxygen consumption rate of a single cell
      using optical interrogation of molecular oxygen sensors placed in micromachined
      micro-wells by temporarily sealing the cells in the micro-traps. The new
      techniques presented here add to the collection of tools available for performing
      "single-cell" biology. A single-cell self-assembly yield of 61% was achieved with
      oxygen draw down rates of 0.83, 0.82, and 0.71 fmol/minute on three isolated live
      A549 cells.

PMID- 20694049
TI  - Solvation Effect on the Conformations of Alanine Dipeptide: Integral Equation
      Approach.
AB  - We present an implicit solvent model based on the extended reference interaction
      site model (XRISM) integral equation theory, which is a molecular theory of
      solvation. The solvation free energy is composed of additive potentials of mean
      force (PMF) of various functional groups. The XRISM theory is applied to
      determine the PMF of each group in water and NaBr electrolyte solutions. The
      method has been coupled to Brownian dynamics (BD) and is illustrated here on
      alanine dipeptide. The results of the method are compared with those obtained by
      explicit water simulations and other popular implicit solvent models for detailed
      discussion. The comparison of our model with other methods indicates that the
      intramolecular correlation and the solvation structure influence the stability of
      the P(II) and alpha(R) conformers. The results of NaBr electrolyte solutions show
      that the concentration of electrolyte also has a substantial effect on the
      favored conformations.

PMID- 20694050
TI  - Negotiated Identities: Male Migration and Left-Behind Wives in India.
AB  - This paper examines the impact of husbands' migration on the lives of women left
      behind. Using data from the India Human Development Survey 2005, we focus on two
      dimensions of women's lives: women's autonomy and control over their lives; and
      women's labour force participation. Results suggest that household structure
      forms the key mediating factor through which husbands' absence affects women.
      Women not residing in extended families are faced with both higher levels of
      responsibilities and greater autonomy, while women who live in extended
      households do not experience these demands or benefits.

PMID- 20694051
TI  - Does Negative Interaction in the Church Increase Depression? Longitudinal
      Findings from the Presbyterian Panel Survey.
AB  - This study examines a neglected topic in research on religion and psychological
      well-being: the effects of negative interaction in church on depression. After
      outlining a series of theoretical arguments linking negative interaction with
      health and well-being, relevant hypotheses are tested using longitudinal data
      from two surveys of the 1997-99 Presbyterian Panel, a nationwide panel of members
      and elders (lay leaders) in congregations of the Presbyterian Church (USA).
      Findings confirm that negative interaction appears to foster or exacerbate
      depression over the study period. In addition, specific dimensions of social
      negativity have distinctive effects; the impact of criticisms on depression
      surface only in cross-sectional models, while the effects of excessive demands
      emerge only in the longitudinal models. No subgroup variations in these effects
      are detected. Implications of these findings are discussed with regard to (a)
      research on religion and health and (b) congregational life, and a number of
      promising directions for future research are elaborated.

PMID- 20694052
TI  - SEMIPARAMETRIC MARGINAL AND ASSOCIATION REGRESSION METHODS FOR CLUSTERED BINARY
      DATA.
AB  - Clustered data arise commonly in practice and it is often of interest to estimate
      the mean response parameters as well as the association parameters. However, most
      research has been directed to inference about the mean response parameters with
      the association parameters relegated to a nuisance role. There is little work
      concerning both the marginal and association structures, especially in the
      semiparametric framework. In this paper, our interest centers on inference on the
      association parameters in addition to the mean parameters. We develop
      semiparametric methods for both complete and incomplete clustered binary data and
      establish the theoretical results. The proposed methodology is illustrated
      through numerical studies.

PMID- 20694053
TI  - A Note on Adapting Propensity Score Matching and Selection Models to Choice Based
      Samples.

PMID- 20694054
TI  - Old-Age Wealth in Mexico: The Role of Reproductive, Human Capital, and Employment
      Decisions.
AB  - The authors examined relationships between the wealth of older adults and their
      early-life decisions regarding investment in human capital, family formation, and
      work activities in Mexico, using the 2001 Mexican Health and Aging Study. The
      authors examined correlates of accumulated financial wealth by gender and across
      three age cohorts: 50 to 59, 60 to 69, and 70 years or older. The authors outline
      the changing context these cohorts experienced during their lifetimes; describe
      patterns of net financial worth by main covariates across groups defined by age,
      sex, and marital status; and present the results of multivariate models of net
      worth. Simulations were conducted to illustrate patterns of net worth associated
      with alternative scenarios depicting differing representative combinations of
      life-course characteristics by age cohort. The findings suggest that old-age
      financial wealth in Mexico is more closely associated with family formation and
      human capital decisions than with employment decisions over the lifetime.

PMID- 20694055
TI  - Community-acquired pneumonia in elderly patients.
AB  - Community-acquired pneumonia continues to have a significant impact on elderly
      individuals, who are affected more frequently and with more severe consequences
      than younger populations. As the population ages it is expected that the medical
      and economic impact of this disease will increase. Despite these concerns, little
      progress has been made in research specifically focusing on community-acquired
      pneumonia in the elderly. Data continue to show that a high index of suspicion,
      early antimicrobial therapy and appropriate medications to cover typical
      pathogens are extremely important in treating community-acquired pneumonia in
      older individuals. This review is designed to serve as an update to our previous
      work published in Aging Health in 2006, with specific emphasis on the most recent
      evidence published since that time.

PMID- 20694056
TI  - Individual flexor tendon identification within the carpal tunnel: A semi
      automated analysis method for serial cross-section MR images.
AB  - Carpal tunnel syndrome is commonly viewed as resulting from chronic mechanical
      insult of the median nerve by adjacent anatomical structures. Both the median
      nerve and its surrounding soft tissue structures are well visualized on magnetic
      resonance (MR) images of the wrist and hand. Addressing nerve damage from
      impingement of flexor digitorum tendons co-occupying the tunnel is attractive,
      but to date has been restricted by lack of means for making individual
      identifications of the respective tendons. In this image analysis work, we have
      developed a region-growing method to positively identify each individual digital
      flexor tendon within the carpal tunnel by tracking it from a more distal MR
      section where the respective tendon identities are unambiguous. Illustratively,
      the new method was applied to MRI scans from four different subjects in a variety
      of hand poses. Conventional shape measures yielded less discriminatory
      information than did evaluations of individual tendon location and arrangement.
      This new method of rapid identification of individual tendons will facilitate
      analysis of tendon/nerve interactions within the tunnel, thereby providing better
      information about mechanical insult of the median nerve.

PMID- 20694058
TI  - Simultaneous Truth and Performance Level Estimation with Incomplete, Over
      complete, and Ancillary Data.
AB  - Image labeling and parcellation are critical tasks for the assessment of
      volumetric and morphometric features in medical imaging data. The process of
      image labeling is inherently error prone as images are corrupted by noise and
      artifact. Even expert interpretations are subject to subjectivity and the
      precision of the individual raters. Hence, all labels must be considered
      imperfect with some degree of inherent variability. One may seek multiple
      independent assessments to both reduce this variability as well as quantify the
      degree of uncertainty. Existing techniques exploit maximum a posteriori
      statistics to combine data from multiple raters. A current limitation with these
      approaches is that they require each rater to generate a complete dataset, which
      is often impossible given both human foibles and the typical turnover rate of
      raters in a research or clinical environment. Herein, we propose a robust set of
      extensions that allow for missing data, account for repeated label sets, and
      utilize training/catch trial data. With these extensions, numerous raters can
      label small, overlapping portions of a large dataset, and rater heterogeneity can
      be robustly controlled while simultaneously estimating a single, reliable label
      set and characterizing uncertainty. The proposed approach enables parallel
      processing of labeling tasks and reduces the otherwise detrimental impact of
      rater unavailability.

PMID- 20694059
TI  - Adolescent Dose and Ratings of an Internet-Based Depression Prevention Program: A
      Randomized Trial of Primary Care Physician Brief Advice versus a Motivational
      Interview.
AB  - BACKGROUND: Internet-based interventions for education and behavior change have
      proliferated, but most adolescents may not be sufficiently motivated to engage in
      Internet-based behavior change interventions. We sought to determine how two
      different forms of primary care physician engagement, brief advice (BA) versus
      motivational interview (MI), could enhance participation outcomes in an Internet
      based depression prevention intervention. METHODS: Eighty-three adolescents at
      risk for developing major depression were recruited by screening in primary care
      and randomized to two groups: BA (1-2 minutes) + Internet program versus MI (10
      15 minutes) + Internet program. We compared measures of participation and
      satisfaction for the two groups for a minimum of 12 months after enrollment.
      RESULTS: Both groups engaged the site actively (MI: 90% versus BA: 78%, p=0.12).
      MI had significantly higher levels of engagement than BA for measures including
      total time on site (143.7 minutes versus 100.2 minutes, p=0.03), number of
      sessions (8.16 versus 6.00, p=0.04), longer duration of session activity on
      Internet site (46.2 days versus 29.34 days, p=0.04), and with more characters
      typed into exercises (3532 versus 2004, p=0.01). Adolescents in the MI group
      reported higher trust in their physician (4.18 versus 3.74, p=0.05) and greater
      satisfaction with the Internet-based component (7.92 versus 6.66, p=0.01).
      CONCLUSIONS: Primary care engagement, particularly using motivational
      interviewing, may increase Internet use dose, and some elements enhance and
      intensify adolescent use of an Internet-based intervention over a one to two
      month period. Primary care engagement may be a useful method to facilitate
      adolescent involvement in preventive mental health interventions.

PMID- 20694060
TI  - Exforge (amlodipine/valsartan combination) in hypertension: the evidence of its
      therapeutic impact.
AB  - INTRODUCTION: Hypertension is an important risk factor for cardiovascular disease
      and its management requires improvement. New treatment strategies are needed.
      AIMS: This review analyses one of these strategies, which is the development of
      effective and safe combination therapy. Indeed, at least two antihypertensive
      agents are often needed to achieve blood pressure control. Exforge((R))
      (Novartis) is a new drug combination of the calcium channel blocker, amlodipine,
      and the angiotensin II receptor blocker, valsartan. EVIDENCE REVIEW: The
      amlodipine/valsartan combination is an association of two well-known
      antihypertensive products with specific targets in cardiovascular protection,
      namely calcium channel blockade and antagonism of the renin-angiotensin
      aldosterone system. This kind of association, with neutral metabolic properties
      and significant antihypertensive efficacy, could be a useful new antihypertensive
      product. Currently available data have shown that this new combination is well
      tolerated and effective even in severe hypertension. CLINICAL VALUE: Clinical
      trials are ongoing for further assessment of the efficacy, compliance, and safety
      of this combination and its congeners. No data exist to prove that the
      amlodipine/valsartan combination is better than other antihypertensive strategies
      for cardiovascular or renal protection, but some trials with other combination
      therapies show such potential advantage.

PMID- 20694061
TI  - Intravenous zoledronic acid for the treatment of osteoporosis: The evidence of
      its therapeutic effect.
AB  - INTRODUCTION: Osteoporosis is a disease characterized by low bone mineral density
      and poor bone quality resulting in reduced bone strength and increased risk of
      fracture. Oral bisphosphonates, first-line therapy for most patients with
      osteoporosis, are associated with suboptimal adherence to therapy due to factors
      that include a complex dosing regimen and gastrointestinal intolerance in some
      patients. Intravenous bisphosphonates address these limitations through
      infrequent injectable dosing that assures 100% bioavailability. Intravenous
      zoledronic acid is the newest bisphosphonate to be approved for the treatment of
      osteoporosis. AIMS: This review assesses the evidence for the therapeutic effects
      of intravenous zoledronic acid for the treatment of osteoporosis. EVIDENCE
      REVIEW: Zoledronic acid 5 mg administered as an annual 15-min intravenous
      infusion has been shown to reduce the risk of vertebral fractures, hip fractures,
      and other fractures in a three-year randomized, double-blind, placebo-controlled
      trial in women with postmenopausal osteoporosis. In a randomized, double-blind,
      placebo-controlled trial in women and men with a recent surgical repair of low
      trauma hip fracture, it reduced the risk of new clinical fractures and improved
      survival. In both studies, zoledronic acid was associated with a good safety
      profile and was generally well tolerated. Zoledronic acid has the potential to
      improve clinical outcomes by reducing the risk of fracture in patients with
      osteoporosis. CLINICAL VALUE: Intravenous zoledronic acid 5 mg every 12 months
      reduces fracture risk in women with postmenopausal osteoporosis and in women and
      men with recent low-trauma hip fracture.

PMID- 20694062
TI  - Febuxostat: the evidence for its use in the treatment of hyperuricemia and gout.
AB  - INTRODUCTION: Gout is a common and disabling cause of arthritis in middle-aged
      and elderly populations, with its main predisposing factor being hyperuricemia
      (serum urate > 6.8 mg/dL). Options for treatment of chronic gout until 2008 were
      allopurinol, a xanthine oxidase inhibitor, and the group of drugs known as
      uricosurics that stimulate the renal excretion of uric acid. A proportion of
      patients, including some with chronic kidney disease and solid organ
      transplantations, could not be treated with the those therapies because of
      intolerance, drug interactions, or adverse events. Febuxostat is a nonpurine
      xanthine oxidase inhibitor, recently approved in Europe and the United States for
      the treatment of chronic gout. AIM: To review the clinical evidence (phase II and
      III studies) of the effectiveness and safety of febuxostat for treatment of
      hyperuricemia and gout. EVIDENCE REVIEW: Febuxostat, at doses ranging from 40 to
      240 mg/day, is efficacious in reducing serum urate in patients with hyperuricemia
      and gout, comparing favorably with fixed doses of allopurinol in that respect.
      Early safety signals with respect to liver test abnormalities and cardiovascular
      outcomes have not been confirmed in recent large prospective trials but need to
      be further monitored. CLINICAL POTENTIAL: Given its low cost and extensive
      clinical experience, allopurinol will likely remain the first-line drug for
      management of hyperuricemia and gout. Febuxostat may provide an important option
      in patients unable to use allopurinol, those with very high serum urate levels,
      or in the presence of refractory tophi.

PMID- 20694063
TI  - Indacaterol: a new once daily long-acting beta(2) adrenoceptor agonist.
AB  - INTRODUCTION: Indacaterol is a novel once daily long-acting beta agonist (LABA)
      developed for the treatment of chronic obstructive pulmonary disease (COPD) and
      asthma. AIMS: This review summarizes preclinical and clinical data of
      indacaterol, including all data generated during the phase II trial program, and
      further discusses the outlook and potential of the drug in the future treatment
      of COPD and asthma. EVIDENCE REVIEW: Clinical studies suggest that indacaterol
      produces rapid and sustained bronchodilation in COPD patients and asthmatics of
      different severities. Until now, clinical studies of up to 28 days' duration have
      been published that have confirmed the suitability of indacaterol for once daily
      dosing, along with a favorable overall safety and tolerability profile. OUTCOMES
      SUMMARY: Indacaterol monotherapy has potential in COPD, where antiinflammatory
      treatment is not fully established and issues about a potential risk of LABA use
      causing excess mortality have not been raised. In addition, indacaterol
      represents an option for future combination therapies in both asthma and COPD.
      However, more data are required, particularly in COPD, to fully assess the
      therapeutic potential of indacaterol in improving symptoms, quality of life,
      exacerbation rates, disease progression, exercise capacity, and hyperinflation.
      The currently ongoing phase III clinical trial program will add knowledge in
      respect to many long-term efficacy outcomes and gather further safety and
      tolerability data in both asthma and COPD.

PMID- 20694064
TI  - Axitinib: The evidence of its potential in the treatment of advanced thyroid
      cancer.
AB  - INTRODUCTION: Thyroid cancer is a rare disease with an incidence of around 37,000
      cases per year. However, its incidence is rising faster than many other cancers
      and for men this disease ranks highest overall in the rate of increase (2.4%
      annual increase) in cancer deaths. As the number of radioactive iodine-resistant
      thyroid cancers increases, the need for newer treatments has become more
      important. Axitinib is one of many new small molecule inhibitors of growth factor
      receptors that have shown promise in the treatment of many cancers. It targets
      the vascular endothelial growth factor receptors 1, 2 and 3. AIMS: The goal of
      this article is to review the published evidence for the use of axitinib in the
      treatment of thyroid cancer and define its therapeutic potential. EVIDENCE
      REVIEW: The major evidence of axitinib activity has appeared in meeting report
      abstracts. One phase II study has been published. This included patients with any
      histological type of thyroid cancer that was not amenable to treatment with
      radioactive iodine. CLINICAL POTENTIAL: To date, in phase II clinical studies
      axitinib has demonstrated antitumor activity in advanced refractory thyroid
      cancer. As a monotherapy it resulted in a 30% response rate with another 38% of
      patients having stable disease. Axitinib appears to have a good tolerability
      profile, with hypertension being the most common grade 3 or greater side effect.

PMID- 20694065
TI  - Eptifibatide: The evidence for its role in the management of acute coronary
      syndromes.
AB  - INTRODUCTION: Acute coronary syndromes and non-Q-wave myocardial infarction are
      often initiated by platelet activation. Eptifibatide is a cyclic heptapeptide and
      is the third inhibitor of glycoprotein (Gp) IIb/IIIa that has found broad
      acceptance after the specific antibody abciximab and the nonpeptide tirofiban
      entered the global market. Gp IIb/IIIa inhibitors act by inhibiting the final
      common pathway of platelet aggregation, and play an important role in the
      management of acute coronary syndromes. AIMS: This review assesses the evidence
      for therapeutic value of eptifibatide as a Gp IIb/IIIa inhibitor in patients with
      acute coronary syndromes. EVIDENCE REVIEW: Several large, randomized controlled
      trials show that eptifibatide as adjunctive therapy to standard care in patients
      with non-ST segment elevation acute coronary syndrome is associated with a
      significant reduction in the incidence of death or myocardial infarction. Data
      are limited regarding the use of eptifibatide in patients with ST segment
      elevation myocardial infarction. Cost-effectiveness analysis indicates that
      eptifibatide is associated with a favorable cost-effectiveness ratio relative to
      standard care. According to US cost-effectiveness analysis about 70% of the
      acquisition costs of eptifibatide are offset by the reduced medical resource
      consumption during the first year. Eptifibatide was well tolerated in most of the
      trials. Bleeding is the most commonly reported adverse event, with most major
      bleeding episodes occurring at the vascular access site. Major intracranial
      bleeds, stroke, or profound thrombocytopenia rarely occurred during eptifibatide
      treatment. PLACE IN THERAPY: Eptifibatide has gained widespread acceptance as an
      adjunct to standard anticoagulation therapy in patients with acute coronary
      syndromes, and may be particularly useful in the management of patients with
      elevated troponin or undergoing percutaneous coronary interventions.

PMID- 20694066
TI  - Desvenlafaxine in major depressive disorder: an evidence-based review of its
      place in therapy.
AB  - INTRODUCTION: Desvenlafaxine, the active metabolite of venlafaxine, is a
      serotonin norepinephrine reuptake inhibitor (SNRI) recently approved for the
      treatment of major depressive disorder. It is one of only three medications in
      this class available in the United States. AIMS: The objective of this article is
      to review the published evidence for the safety and efficacy of desvenlafaxine,
      and to compare it to other antidepressants to delineate its role in the treatment
      of depression. EVIDENCE REVIEW: At the recommended dose of 50 mg per day the rate
      of response and remission was similar to other SNRIs, as was the adverse effect
      profile. The rate of discontinuation was no greater than placebo, and a
      discontinuation syndrome was not observed at this dose. Higher doses were not
      associated with greater efficacy, but they did lead to more side effects, and the
      use of a taper prior to discontinuation. The most common side effects reported
      were insomnia, somnolence, dizziness, and nausea. Some subjects experienced
      clinically significant blood pressure elevation. PLACE IN THERAPY: Like
      duloxetine, desvenlafaxine inhibits the reuptake of both norepinephrine and
      serotonin at the starting dose. Dual reuptake inhibitors have been shown to have
      small but statistically significantly greater rates of response and remission
      compared to selective serotonin reuptake inhibitors, and they have also shown
      early promise in the treatment of neuropathic pain. Desvenlafaxine may prove to
      be a valuable treatment option by expanding the limited number of available dual
      reuptake inhibitors.

PMID- 20694067
TI  - Conivaptan: Evidence supporting its therapeutic use in hyponatremia.
AB  - INTRODUCTION: The available treatment options for euvolemic and hypervolemic
      hyponatremia are limited, and consist mainly of fluid restriction, diuresis, or
      hypertonic solutions. Most of these therapies are neither well tolerated nor
      totally effective, and many are associated with significant adverse effects.
      Vasopressin receptor antagonists, also known as vaptans, are a new class of
      agents that now offer an additional treatment option for hyponatremic patients.
      Conivaptan hydrochloride, a competitive antagonist of vasopressin V1a and V2
      receptors, is the first agent in this class to be approved for treatment of
      euvolemic and hypervolemic hyponatremia in hospitalized patients. AIMS: This
      review critically assesses the evidence that support the use of conivaptan for
      the treatment of patients with euvolemic and hypervolemic hyponatremia. EVIDENCE
      REVIEW CONCLUSION: Conivaptan is effective in raising serum sodium levels in a
      predictable and safe fashion in euvolemic and hypervolemic hyponatremic patients.
      Conivaptan provides the first molecularly targeted approach for correcting
      hyponatremia in hospitalized patients.

PMID- 20694068
TI  - Temozolomide: The evidence for its therapeutic efficacy in malignant
      astrocytomas.
AB  - INTRODUCTION: Malignant gliomas are a heterogeneous group of primary central
      nervous system neoplasms that represent less than 2% of all cancers yet carry a
      significant burden to society. They are frequently associated with considerable
      and progressive neurological disability and are ultimately intractable to all
      forms of treatment. Temozolomide (TMZ) is a new second generation DNA alkylating
      agent that has become part of malignant astrocytoma management paradigms because
      of its proven efficacy, ease of administration, and favorable toxicity profile.
      AIMS: To review the role of TMZ in the management of malignant astrocytomas
      (World Health Organization grades III and IV) including newly diagnosed (n) and
      recurrent (r) anaplastic astrocytomas (AA) and glioblastomas. EVIDENCE REVIEW: A
      series of pivotal clinical trials have established a role for TMZ in the
      treatment of malignant astrocytomas. A large phase II trial examining the role of
      TMZ in rAA showed a response rate of 35%, and a 6-month progression-free survival
      of 46%. This led to the accelerated approval of TMZ by the FDA and the EU for the
      treatment of rAA. Evidence for a role of TMZ in nAA is currently limited but
      research is ongoing in this area. The role of TMZ in the management of
      glioblastoma at the time of recurrence (rGBM) is less impressive but evidence for
      its activity was demonstrated in two large phase II trials that led to the
      approval of TMZ for this indication in Europe and Canada but not in the US. A
      recent large prospective randomized phase III trial showed that the addition of
      TMZ during and after radiation therapy (RT) in newly diagnosed (nGBM) patients
      prolonged median overall survival by 2.5 months; perhaps more importantly, the 2
      year survival rate for patients receiving TMZ and RT was 26% compared with 10%
      for those receiving RT alone. Concurrent TMZ with RT followed by adjuvant TMZ has
      become the standard of care for nGBM patients. Based on the evidence presented in
      this trial, TMZ received approval from the FDA and the EU for patients with nGBM
      in 2005. PLACE IN THERAPY: THERE IS EVIDENCE TO SUPPORT THE USE OF TMZ FOR THE
      FOLLOWING DISEASES IN THE ORDER OF MOST TO LEAST CONVINCING: nGBM, rAA, rGBM, and
      nAA. This order may quickly change as more trials are being designed and
      implemented, particularly with novel TMZ dosing schedules.

PMID- 20694069
TI  - Lasofoxifene: Evidence of its therapeutic value in osteoporosis.
AB  - INTRODUCTION: Osteoporosis is a skeletal disorder characterized by compromised
      bone strength and increased risk of fracture. It is a common disorder in elderly
      subjects and represents a major public health problem, affecting up to 40%
      postmenopausal women and 15% of men. Among the several therapeutical
      interventions, hormone replacement therapy (HRT) was traditionally seen as the
      gold standard for preventing osteoporotic fractures in postmenopausal women, as
      well as for the management of menopausal symptoms. However HRT, especially if
      administered long-term, may lead to an increased risk of breast and, when
      unopposed by progestins, endometrial cancers. Alternative therapies include
      bisphosphonates and raloxifene, a selective estrogen receptor modulator (SERM).
      While the former have been associated with suboptimal adherence, the latter was
      considerably less potent than estrogen and its effect in the prevention of
      nonvertebral fractures remain uncertain. AIMS: The purpose of this article is to
      review the clinical trials of lasofoxifene, a new SERM for the treatment of
      postmenopausal osteoporosis. The medical literature was reviewed for appropriate
      articles containing the terms "lasofoxifene" and SERMs". EVIDENCE REVIEW: There
      are three (phase II or phase III) clinical trials that clearly demonstrate
      efficacy and safety of this new SERM in the suppression of bone loss and the
      prevention of vertebral and nonvertebral fractures. Moreover, lasofoxifene
      treatment also reduced breast cancer risk and the occurrence of vaginal atrophy.
      PLACE IN THERAPY: With its increased potency and efficacy on the prevention of
      nonvertebral fractures lasofoxifene may be an alternative and cost-effective
      therapy for osteoporosis in postmenopausal women.

PMID- 20694070
TI  - Raltegravir: The evidence of its therapeutic value in HIV-1 infection.
AB  - INTRODUCTION: The antiretroviral treatment paradigm for human immunodeficiency
      virus-1 (HIV-1) infection has undergone a significant change with the addition of
      a new class of therapeutic agents targeting HIV-1 integrase (IN). IN inhibitors
      prevent the integration of viral DNA into the human genome and terminate the
      viral life cycle. As the first member of this new class of anti-HIV drugs,
      raltegravir has shown promising results in the clinic. AIMS: To review the
      emerging evidence for the use of the IN inhibitor raltegravir in the treatment of
      HIV-1 infection. EVIDENCE REVIEW: Strong evidence shows that raltegravir is
      effective in reducing the viral load to less than 50 copies/mL and increasing CD4
      cell count in treatment-experienced patients with triple-drug class-resistant HIV
      1 infection. Substantial evidence also indicates that while raltegravir is able
      to achieve treatment response in patients with drug-resistant HIV-1, it is
      susceptible to development of resistance. Raltegravir should be used with at
      least one other active drug. In addition to its use in salvage therapy upon
      failure of first-line antiretroviral treatment, a raltegravir-based treatment
      regimen may also be effective as initial therapy. Substantial evidence also shows
      that raltegravir-based treatment regimen is well tolerated with minimal
      clinically severe adverse events and toxicities. Modeling studies suggest a cost
      effectiveness of US$21,339 per quality-adjusted life year gained with raltegravir
      use, though further direct evidence on quality of life and cost-effectiveness is
      needed. PLACE IN THERAPY: Raltegravir shows significant and sustained virologic
      and immunologic response in combination with other antiretrovirals in treatment
      experienced HIV-1 infected patients who show evidence of viral replication or
      multidrug-resistant HIV-1 strains, without any significant tolerability issues.

PMID- 20694071
TI  - Etravirine (TMC-125): The evidence for its place in the treatment of HIV-1
      infection.
AB  - INTRODUCTION: Etravirine is a novel nonnucleoside reverse transcriptase inhibitor
      (NNRTI) specifically designed to suppress the replication of viruses resistant to
      the three currently approved NNRTIs efavirenz, nevirapine, and delavirdine. AIMS:
      To assess the evidence for the place of etravirine in the treatment of HIV-1
      infection. EVIDENCE REVIEW: In combination with a ritonavir-boosted protease
      inhibitor etravirine has demonstrated high antiviral activity against strains
      exhibiting up to three NNRTI resistance mutations. The drug appears to be well
      tolerated, with only nausea and rash occuring significantly more frequently with
      etravirine compared with placebo. Of note, neuropsychologic side effects that
      frequently limit the use of efavirenz were not reported more frequently with
      etravirine. PLACE IN THERAPY: Given its high activity against most NNRTI
      resistant strains and its very good tolerability, etravirine is of high value for
      pretreated patients with NNRTI resistance and protease inhibitor exposure.
      Efforts should be made to demonstrate activity in switching strategies (due to
      toxicity) and earlier lines of failure or in the setting of primary NNRTI
      resistance in order to explore the potential of the drug beyond salvage therapy.

PMID- 20694072
TI  - Golimumab: A novel human anti-TNF-alpha monoclonal antibody for the treatment of
      rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis.
AB  - INTRODUCTION: The introduction of tumor necrosis factor-alpha (TNF-alpha)
      inhibitors represented a significant advance in the management of rheumatoid
      arthritis (RA) and other chronic inflammatory diseases. Although three TNF-alpha
      inhibitors have been approved for the treatment of RA by the US Food and Drug
      Administration (FDA) and the European Medicinal Products Evaluation Agency
      (EMEA), not all patients achieve a satisfactory clinical improvement with these
      therapeutic agents. The mode of administration of these medications is
      inconvenient for some patients. AIMS: Golimumab is a novel anti-TNF-alpha
      monoclonal antibody that is in clinical development for the treatment of RA,
      psoriatic arthritis (PsA), and ankylosing spondylitis (AS), either as a first
      line biologic therapy or an alternative after other TNF-alpha inhibitors have
      been discontinued. This review summarizes the development of, and clinical
      evidence achieved with, golimumab. EVIDENCE REVIEW: Golimumab has demonstrated
      significant efficacy in randomized, double-blind, placebo-controlled trials when
      administered subcutaneously once every four weeks. It has been generally well
      tolerated in clinical trials and demonstrates a safety profile comparable with
      currently available TNF-alpha inhibitors. OUTCOMES SUMMARY: Golimumab has been
      confirmed to be an effective treatment for patients with RA, PsA, and AS in phase
      III clinical trials as evaluated by traditional measures of disease activity,
      such as signs and symptoms, as well as measures of physical function, patient
      reported outcomes, and health economic measures. The efficacy and safety profile
      of golimumab in RA, PsA, and AS appears to be similar to other anti-TNF agents.
      However, golimumab has the potential advantage of once monthly subcutaneous
      administration and the possibility of both subcutaneous and intravenous
      administration.

PMID- 20694073
TI  - Agomelatine: The evidence for its place in the treatment of depression.
AB  - INTRODUCTION: Depressive disorders are among the main causes of disability due to
      disease. In spite of recent progress in the pharmacotherapy of depression, there
      is still a high nonresponse rate of approximately 30% to the first antidepressant
      treatment. Furthermore, the latency of several weeks until sufficient clinical
      improvement and the risk of side effects remain unresolved problems. Therefore,
      there is still further need for the development of new antidepressants. In the
      last years a variety of melatonin receptor agonists have been synthesized and
      evaluated for the treatment of sleep disorders. Animal studies suggested that
      agomelatine (S-20098), a synthetic melatonergic MT(1) and MT(2) receptor agonist
      with serotonin receptor antagonistic properties, may have additional activating
      properties and may represent a new approach in the treatment of depression. AIMS:
      Clinical trials that have demonstrated efficacy and safety of agomelatine for the
      treatment of depression are reviewed. EVIDENCE REVIEW: In clinical trials,
      including phase III studies, superior efficacy compared to placebo and good
      efficacy compared to standard antidepressants was shown for agomelatine for the
      acute treatment of major depression. In all studies published so far agomelatine
      was safe and the overall tolerability profile was superior to selective serotonin
      reuptake inhibitors or selective serotonin and norepinephrine reuptake
      inhibitors. PLACE IN THERAPY: Agomelatine may represent a novel perspective in
      the treatment of acute depression. The improvement of sleep disturbances, the
      tolerability in terms of sexual side effects, and the lack of withdrawal symptoms
      after abrupt discontinuation of treatment may represent important clinical
      benefits compared to established antidepressants.

PMID- 20694074
TI  - Tocilizumab: The evidence for its place in the treatment of juvenile idiopathic
      arthritis.
AB  - INTRODUCTION: Juvenile idiopathic arthritis (JIA) is one of the most common
      chronic diseases with childhood onset. It comprises different subtypes of which
      the systemic onset subtype is often resistant to treatment. With the advent of
      biological treatment with tumor necrosis factor-alpha (TNFalpha)-inhibitors, the
      clinical outcome of JIA has improved considerably, but only for subtypes other
      than systemic JIA. Substantial evidence shows that the proinflammatory cytokine
      interleukin-6 (IL-6) plays a pivotal role in systemic JIA. The blockage of IL-6
      action by tocilizumab, a humanized anti-IL-6-receptor monoclonal antibody, could
      therefore be an effective treatment of systemic JIA. AIMS: The purpose of this
      article was to review the clinical trials of tocilizumab and to discuss its place
      in the treatment of JIA with the focus on the systemic onset of disease. EVIDENCE
      REVIEW: Two phase II studies and one phase III clinical trial of tocilizumab
      demonstrating the clinical efficacy and safety in systemic onset JIA have been
      published. Within those studies, sustained and high response rates of clinical
      improvement have been achieved with American College of Rheumatology Pediatric
      criteria (ACRPed) 30, 50, and 70 observed in 98%, 94%, and 90% of patients,
      respectively, after 48 weeks. One study regarding the clinical efficacy of
      tocilizumab for the treatment of oligo- and polyarticular JIA has been presented
      only as a conference abstract. PLACE IN THERAPY: The very promising results seen
      so far in patients with severe systemic JIA and acceptable tolerability gives
      tocilizumab a central role in the future therapy in controlling this disease. No
      other biological therapy has achieved similar high response rates when treating
      with tocilizumab 8 mg/kg every two weeks to patients with systemic onset JIA, but
      direct comparison of the efficacy of different biological agents are not yet
      available.

PMID- 20694075
TI  - Trabectedin: the evidence for its place in therapy in the treatment of soft
      tissue sarcoma.
AB  - INTRODUCTION: Soft tissue sarcoma accounts for less than 1% of all malignant
      neoplasms and is comprised of a very heterogeneous group of tumors with over 50
      different subtypes. Due to its diversity and rarity, developing new therapeutics
      has been difficult, at best. The standard of care in the treatment of advanced
      and metastatic disease over the last 30 years has been doxorubicin and
      ifosfamide, either alone or in combination. There has been significant focus on
      developing new therapeutics to treat primary and metastatic disease. Trabectedin
      (ecteinascidin-743) is a tetrahydroiso-quinoline alkaloid which has been
      evaluated in the treatment of metastatic soft tissue sarcoma. AIMS: To review the
      current evidence for the therapeutic use of trabectedin in patients with soft
      tissue sarcoma. EVIDENCE REVIEW: Five phase I studies in patients with solid
      tumors, all of which include sarcoma patients, evaluating the dosing and toxicity
      of trabectedin were performed with efficacy being evaluated as a secondary
      endpoint. Additionally, there are four phase I trials evaluating trabectedin in
      combination with frontline therapeutic drugs in soft tissue sarcoma. Four phase
      II studies were performed in soft-tissue sarcoma patients with objective response
      rates ranging from 3.7% to 17.1%. Additionally, in two compassionate use trials,
      objective response rates between 14% and 51% were seen, the largest response
      resulting from a study specifically focusing on liposarcoma. PLACE IN THERAPY:
      Trabectedin is a potential therapeutic option for the management of soft-tissue
      sarcoma. It appears to have specific activity in a select group of histologies,
      most notably myxoid/round cell liposarcoma. Although it would be helpful to study
      the use of trabectedin in a randomized, controlled fashion, the relative rarity
      of soft-tissue sarcoma, and heterogeneity of the histologic subtypes, makes phase
      III trials a difficult prospect.

PMID- 20694076
TI  - Efficacy of palifermin (keratinocyte growth factor-1) in the amelioration of oral
      mucositis.
AB  - PURPOSE: Oral mucositis is a significant toxicity of cytotoxic chemo- and
      radiation-therapy used to treat cancer. Palifermin is the first
      pharmaceutical/biological agent approved for the intervention of oral mucositis.
      The major objective of this review is to evaluate the evidence supporting the use
      of palifermin. METHODS: A literature search was performed using an appropriate
      keyword search in MEDLINE and PubMed databases. RESULTS: Of 100 full papers and 4
      abstracts identified, 12 papers and 3 abstracts were appropriate for analysis.
      Level 2 evidence supporting palifermin use in patients with hematologic
      malignancies being treated with autologous hematopoietic stem cell
      transplantation (HSCT) is clear. Level 2 evidence also exists for the use of
      palifermin in the prevention of oral mucositis in patients with solid tumors
      (colorectal cancer, head and neck cancer), but is incomplete. Level >/= 3 data
      support the use of palifermin in allogeneic HSCT recipients and cycled
      chemotherapy. A single health economic study concluded that palifermin is
      essentially cost neutral in the autologous HSCT population. CONCLUSION: Data
      supporting the use of palifermin in autologous HSCT recipients with hematologic
      malignancies is clear. Some data exist demonstrating its efficacy in other
      oncologic indications. Additional studies are needed to broaden the potential
      applications of palifermin and to ascertain its economic, but not symptomatic,
      effectiveness.

PMID- 20694077
TI  - Nilotinib for the treatment of chronic myeloid leukemia: An evidence-based
      review.
AB  - INTRODUCTION: Chronic myelogenous leukemia (CML) is a progressive and often fatal
      hematopoietic neoplasm. The Bcr-Abl tyrosine kinase inhibitor imatinib mesylate
      represented a major therapeutic advance over conventional CML therapy, with more
      than 90% of patients obtaining complete hematologic response, and 70%-80% of
      patients achieving a complete cytogenetic response. Despite the high efficacy of
      imatinib, a minority of patients in chronic phase CML and more patients in
      advanced phases are resistant to imatinib, or develop resistance during
      treatment. This is attributed, in 40% to 50% of cases, to the development of
      mutations in the Bcr-Abl tyrosine kinase domain that impair imatinib binding.
      Attempts to circumvent resistance led to the discovery of nilotinib (Tasigna), a
      novel, potent and selective oral Bcr-Abl kinase inhibitor. AIMS: To review the
      evidence for the use of nilotinib in the management of CML. EVIDENCE REVIEW:
      Preclinical and clinical investigations demonstrate that nilotinib effectively
      overcomes imatinib resistance, and has further improved the treatment of CML.
      PLACE IN THERAPY: Nilotinib is currently indicated for patients with CML in
      chronic and accelerated phases following imatinib failure. Randomized studies are
      ongoing to assess the efficacy of nilotinib in patients with newly diagnosed CML.

PMID- 20694078
TI  - Lenalidomide in multiple myeloma: an evidence-based review of its role in
      therapy.
AB  - INTRODUCTION: Multiple myeloma (MM) is a relatively common and incurable
      hematological malignancy. Currently, there is no single standard therapy, with
      choice of treatment dependent on individual patient factors. Lenalidomide is an
      immunomodulatory drug with potent antitumor, antiangiogenic, immunomodulatory,
      and proapoptotic activity in MM. AIMS: To evaluate the evidence for the use of
      lenalidomide in its current indication in relapsed or refractory MM, and
      additionally its investigational use for the treatment of newly diagnosed MM.
      EVIDENCE REVIEW: In patients with relapsed and refractory MM, adding lenalidomide
      to high-dose dexamethasone significantly improves response rates and time-to
      progression, relative to high-dose dexamethasone alone. This translates into a
      significant extension of overall survival (with a median extension of 9.1 months
      in a pivotal phase III study). Outcome is independent of patient age, number of
      previous therapies, type of previous therapy (including thalidomide or autologous
      stem cell transplantation), renal impairment, and beta(2)-microglobulin level.
      Evidence suggests that combining lenalidomide with low-dose dexamethasone
      improves outcomes in patients with newly diagnosed disease and is superior to
      lenalidomide combined with high-dose dexamethasone. Myelosuppression is the
      predominant toxicity observed, although some studies have shown high incidences
      of venous thromboembolism in the absence of prophylactic antithrombotic
      anticoagulation therapy. There is currently only limited evidence regarding the
      health economics of lenalidomide. ROLE IN THERAPY: The encouraging results
      obtained with lenalidomide alone and in combination with dexamethasone in
      patients with relapsed or refractory MM have led to its adoption as a recommended
      therapy in patients who have received at least one prior treatment. Emerging
      evidence supports the ongoing investigation of lenalidomide in combination with
      low-dose dexamethasone, and in other combinations including bortezomib, for use
      both in relapsed, refractory, and newly diagnosed MM.

PMID- 20694079
TI  - Methylnaltrexone: the evidence for its use in the management of opioid-induced
      constipation.
AB  - INTRODUCTION: Constipation is a distressing side effect of opioid treatment,
      being so irksome in some cases that patients would rather suffer the pain than
      the side effect of opioid analgesics. Stool softeners or stimulating laxatives
      are often ineffective or even aggravate the situation. A new efficacious and safe
      drug is needed to limit the frequently observed side effects induced by effective
      opioid-based analgesic therapy and to improve the quality of life for patients,
      most of whom are impaired by a severe disease. AIMS: The purpose of this article
      is to assess current evidence supporting the use of the peripherally acting mu
      opioid receptor antagonist, methylnaltrexone, to restrict passage across the
      blood-brain barrier in patients with opioid-induced bowel dysfunction. EVIDENCE
      REVIEW: There are now convincing data from phase II and multicenter phase III
      randomized, double-blind, placebo-controlled trials that methylnaltrexone induces
      laxation in patients with long-term opioid use without affecting central
      analgesia or precipitation of opioid withdrawal. Onset of the effect is rapid and
      improvement is maintained for at least 3 months during the drug treatment. The
      action of methylnaltrexone is dose dependent. Weight-related dosing appeared to
      be effective. There were no severe side effects or signs of opioid withdrawal.
      Adverse events, most frequently abdominal cramping or nausea, were usually mild
      to moderate. Methylnaltrexone is contraindicated in patients with known or
      suspected mechanical intestinal stenosis. Patients receiving methylnaltrexone
      must be monitored. PLACE IN THERAPY: Methylnaltrexone applied subcutaneously
      every other day may be given to patients suffering from chronic constipation due
      to opioid therapy for whom laxatives do not provide adequate relief of their
      symptoms.

PMID- 20694080
TI  - Ivabradine: the evidence of its therapeutic impact in angina.
AB  - INTRODUCTION: Stable angina pectoris (SAP) is a widely prevalent disease
      affecting 30 000 to 40 000 per million people in Europe and the US. SAP is
      associated with reductions in quality of life and ability to work, and increased
      use of healthcare resources. Ivabradine is a drug with a unique therapeutic
      target, the I(f) current of the sinus node, developed for the treatment of
      cardiovascular diseases including SAP. It has an exclusive heart rate reducing
      effect, without any negative effect on left ventricular function or coronary
      vasodilatation. AIMS: The aim of this paper is to review the evidence concerning
      the use of ivabradine in the treatment of SAP. EVIDENCE REVIEW: Ivabradine is an
      effective antianginal and antiischemic drug, not inferior to the beta blocker
      atenolol and the calcium channel antagonist (CCA) amlodipine. It decreases the
      frequency of angina attacks and increases the time to anginal symptoms during
      exercise. Because of its exclusive chronotropic effect, ivabradine is not
      associated with the typical adverse reactions associated with beta blockers or
      other antianginal drugs. CLINICAL VALUE: Clinical evidence shows that ivabradine
      is a very good antiischemic and antianginal agent, being as effective as beta
      blockade and CCA therapy in controlling myocardial ischemia and symptoms of
      stable angina. Ongoing studies will determine the potential of ivabradine to
      improve morbidity and mortality in coronary artery disease and heart failure.

PMID- 20694081
TI  - Vildagliptin: the evidence for its place in the treatment of type 2 diabetes
      mellitus.
AB  - INTRODUCTION: Type 2 diabetes is increasing in prevalence worldwide and is a
      leading cause of morbidity and mortality, mainly due to the development of
      complications. Vildagliptin is an inhibitor of dipeptidyl peptidase 4 (DPP-4), a
      new class of oral antidiabetic agents. AIMS: To evaluate the role of vildagliptin
      in the management of type 2 diabetes. EVIDENCE REVIEW: Clear evidence shows that
      vildagliptin improves glycemic control (measured by glycosylated hemoglobin and
      blood glucose levels) more than placebo in adults with type 2 diabetes, either as
      monotherapy or in combination with metformin. Vildagliptin is as effective as
      pioglitazone and rosiglitazone, and slightly less effective than metformin,
      although better tolerated. Further glycemic control is achieved when adding
      vildagliptin to metformin, pioglitazone, or glimepride. There is evidence that
      vildagliptin improves beta-cell function and insulin sensitivity. Vildagliptin
      does not appear to be associated with weight gain or with a higher risk of
      hypoglycemia than placebo or other commonly used oral antidiabetic agents.
      Economic evidence is currently lacking. PLACE IN THERAPY: Vildagliptin improves
      glycemic control with little if any weight gain or hypoglycemia in adult patients
      with type 2 diabetes when given alone or in combination with metformin,
      thiazolidinediones, or sulfonylureas. Since many diabetic patients require
      combination therapy, the complementary mechanism of action of vildagliptin and
      other commonly prescribed antidiabetic drugs represents an important new
      therapeutic option in diabetes management.

PMID- 20694082
TI  - Tolvaptan: the evidence for its therapeutic value in acute heart failure
      syndrome.
AB  - INTRODUCTION: Acute heart failure syndrome (AHFS) is one of the leading causes of
      hospital admission in the US. Tolvaptan is a vasopressin V(2) receptor antagonist
      that blocks the effect of arginine vasopressin (AVP) in reabsorbing water from
      the collecting ducts of the nephrons in congestive heart failure. AIMS: To review
      the evidence for utilizing tolvaptan in the treatment of AHFS. EVIDENCE REVIEW:
      Several clinical trials have sought to assess the clinical effects of tolvaptan
      in heart failure. Compared with placebo, tolvaptan has been shown to reduce
      bodyweight and improve serum sodium in patients with AHFS without worsening renal
      function. Tolvaptan appeared to be well tolerated with a good safety profile. It
      caused a significant reduction in pulmonary capillary wedge pressure compared
      with placebo, but has yet to demonstrate reversal of cardiac remodeling. A large
      scale mortality trial showed no differences in long-term mortality rates between
      tolvaptan and placebo, although early symptom relief was apparent with tolvaptan
      and lower diuretic use. PLACE IN THERAPY: Tolvaptan has shown to be safe and
      effective in treating congestion in AHFS. Free water excretion in fluid
      overloaded patients vulnerable to cardiorenal compromise with standard diuretic
      therapy makes V(2) vasopressin receptor blockade an attractive adjunct to
      standard medical therapy aimed at reducing congestion in AHFS.

PMID- 20694083
TI  - Prucalopride: the evidence for its use in the treatment of chronic constipation.
AB  - INTRODUCTION: Chronic constipation is a common condition that is difficult to
      treat. Existing options for the treatment of patients with different subgroups of
      constipation are limited. A new efficacious and safe drug is needed to limit the
      frequently observed adverse effects induced by laxatives, to improve general
      wellbeing and quality of life, and to provide an alternative for enemas or even
      resectional surgery in patients in whom stimulant laxatives cause disabling
      adverse effects or fail to increase bowel movement frequency. AIMS: The purpose
      of this article is to assess the current evidence supporting the use of the
      selective and high affinity serotonin-4 (5-HT(4)) receptor agonist prucalopride
      in the management of chronic constipation. EVIDENCE REVIEW: There are now
      convincing data from phase II and multicenter phase III randomized, double-blind,
      placebo-controlled trials that prucalopride treatment results in a clinically
      meaningful increase in the number of spontaneous complete bowel movements, a
      reduction of perceived severity of symptoms and improved disease-related quality
      of life in a significant proportion of patients. There is a rapid onset of the
      effect and the improvement is maintained for at least 12 weeks. Prucalopride in a
      dose of up to 4 mg per day appeared generally well tolerated and devoid of
      serious cardiac events. Adverse events, most frequently headache and nausea, are
      usually mild or moderate and occur mainly during the first days of treatment.
      Prucalopride should be used with prudence and with careful assessment of the
      benefit-risk ratio until more clinical and electrophysiologic data become
      available, because relatively few patients have been exposed to the drug for long
      periods of time. PLACE IN THERAPY: Prucalopride 1-2 mg once daily may be given to
      patients suffering from chronic constipation for whom laxatives do not provide
      adequate relief of their symptoms. Patients with severe constipation and slow
      transit, who frequently develop tolerance to stimulant laxatives, are also
      eligible for prucalopride treatment.

PMID- 20694084
TI  - Omalizumab: the evidence for its place in the treatment of allergic asthma.
AB  - INTRODUCTION: Asthma is a chronic inflammatory airways disease associated with
      reversible airflow obstruction and bronchial hyperresponsiveness. Asthma is
      prevalent worldwide and results in significant morbidity, mortality, and
      healthcare costs, the majority of which arise from those with severe disease.
      Omalizumab is a monoclonal antibody to immunoglobulin E (IgE) that has been
      developed for the treatment of severe persistent allergic (IgE mediated) asthma.
      AIMS: The aim of this review is to evaluate the available clinical evidence on
      omalizumab to determine the role it has to play in the treatment of persistent
      allergic asthma. EVIDENCE REVIEW: There is clear evidence to show that omalizumab
      is effective in reducing the rate of asthma exacerbations, inhaled corticosteroid
      dose, and the need for rescue medication in patients with allergic asthma.
      Clinical data indicate beneficial effects on patient-reported symptoms and
      perceived quality of life, as well as a reduction in unscheduled healthcare
      visits. There is little evidence to suggest omalizumab may enhance lung function
      or reduce the requirement for oral corticosteroids. Omalizumab has a favorable
      safety profile, although anaphylaxis has occurred. A study in children showed
      similar results to those achieved in adults and adolescents, with fewer asthma
      exacerbations and school days missed. Omalizumab may be cost effective in
      patients when used as add-on therapy to inhaled corticosteroids and long-acting
      beta(2) agonists (LABA). PLACE IN THERAPY: Omalizumab is an effective add-on
      therapy to inhaled corticosteroids and LABAs in adults and adolescents with
      severe persistent allergic asthma. Currently there is insufficient evidence to
      support the use of omalizumab in children.

PMID- 20694085
TI  - Histological changes in the human prostate after radiotherapy and salvage high
      intensity focused ultrasound.
AB  - The histological changes (both macroscopic and microscopic) in the prostate
      following the combination of external beam radiotherapy and salvage high
      intensity focused ultrasound (HIFU) have not been previously described. This
      article describes the case of a 65-year-old male who presented with recurrent
      localized prostate cancer after undergoing external beam radiotherapy for low
      risk prostate cancer. He was treated with salvage HIFU, and 4 weeks later
      presented with symptoms and signs consistent with a prostatorectal fistula.
      During a period of conservative management, his serum prostate-specific antigen
      levels started rising after having reached a nadir. A radical cystoprostatectomy
      and repair of fistula were performed after conservative management failed.
      Histological changes of dense fibrosis were noted in the region where the
      prostate should have been located. A literature review of the histological
      findings in the prostate after HIFU is discussed in this article, as well as the
      available evidence for the management of patients with local failure after the
      combination of external beam radiotherapy and salvage HIFU.

PMID- 20694086
TI  - Malignant melanoma representing with testicular metastasis: a case report and
      review of the literature.
AB  - We present the case of a 52-year-old man, with a history of malignant melanoma,
      who presented with a testicular lump. Radical orchidectomy confirmed a metastatic
      malignant melanoma. We discuss salient features of this disease in the light of
      the published literature.

PMID- 20694087
TI  - Antegrade balloon occlusion of inferior vena cava during thrombectomy for renal
      cell carcinoma.
AB  - Nephrectomy with inferior vena cava (IVC) thrombectomy for advanced renal cell
      carcinoma (RCC) is a challenging and morbid surgical case. We describe the use of
      a simple endoluminal technique to occlude the suprahepatic IVC during
      thrombectomy. A 60-year-old male presented with a large right-sided RCC and IVC
      tumour thrombus. The tip of the thrombus, which was non-adherent to the caval
      wall, extended to the level of the hepatic veins. After complete dissection of
      the kidney, we obtained suprahepatic control of the IVC by a large compliant
      balloon, introduced through the right internal jugular vein and inflated just
      below the level of the diaphragm. The IVC thrombectomy was performed in a
      bloodless field. Mean blood pressure remained stable during IVC balloon inflation
      with a total occlusion time of 10 minutes. Intraprocedural completion cavogram
      and postoperative Doppler ultrasonography showed no residual IVC clot. Blood loss
      during the thrombectomy portion of the case was scant. The patient's
      postoperative course was uncomplicated and, at the last follow-up, he had stable
      metastatic disease on sunitinib therapy. For the surgical treatment of RCC with
      retrohepatic IVC tumour extension, transjugular balloon occlusion of the
      suprahepatic IVC offers an alternative to extensive hepatic mobilization to
      obtain suprahepatic thrombus control. Advantages over traditional surgical
      methods may include decreased surgical time, lower risk of liver injury and
      tumour embolism. We suggest this method for further evaluation.

PMID- 20694088
TI  - Myxoid chondrosarcoma of the scrotum: a case report and review of the literature.
AB  - Extraskeletal myxoid chondrosarcomas are relatively rare soft tissue malignant
      tumours, most commonly located in the extremities. Their occurrence in the
      genitourinary tract is extremely rare. We present a clinical case report of an
      extraskeletal myxoid chondrosarcoma originating in the scrotum.

PMID- 20694089
TI  - Primary testicular mucinous neoplasms: case report and literature review.
AB  - Testicular epithelial mucinous tumours are an extremely rare, but interesting
      form of testicular neoplasm. We reviewed the medical literature using PubMed
      search terms: testis, mucinous cystadenoma, mucinous cystadenocarcinoma,
      neoplasms and testicular neoplasms. We describe a case from our institution and
      provide a review of the literature. Only 11 previously reported cases of mucinous
      testicular tumours have been reported in the English literature. The natural
      history of these tumours is poorly understood, due to their rarity, but it
      appears that, like their ovarian counterparts, they have an excellent prognosis.
      Exclusion of metastasis is an important point for the urologist when encountering
      a mucinous testicular tumour, as metastatic cystic lesions may mimic a primary
      mucinous tumour. We describe a case of ossified testicular mucinous tumour of low
      malignant potential. Such tumours are common in the ovary, but arise very rarely
      in the testicle. The clinical and histological features of this tumour are
      presented, and previously reported cases are reviewed to highlight important
      clinical features.

PMID- 20694090
TI  - Outpatient tubeless percutaneous nephrolithotomy: the initial case series.
AB  - INTRODUCTION: Percutaneous nephrolithotomy (PCNL) has traditionally been
      performed on an inpatient basis. To the best of our knowledge, this is the first
      report of tubeless PCNL on a completely outpatient basis. The purposes of this
      study were to assess the safety and efficacy of outpatient PCNL. METHODS: We
      reviewed the initial consecutive outpatient tubeless PCNLs performed at our
      institution by a single surgeon. Patients were discharged home the day of surgery
      only after meeting strict discharge criteria. Preoperative, intraoperative and
      postoperative data were collected prospectively. RESULTS: Outpatient tubeless
      PCNL was performed in 3 patients. The mean maximum stone diameter was 14 mm. The
      average hospital stay was 175 minutes. All 3 patients were discharged home in
      stable condition after meeting all of the inclusion criteria. There were no
      emergency room visits or hospital readmissions postoperatively. The mean follow
      up period was 47 days. All stones were calcium oxalate and the stone free rate
      was 100%. There were no minor or major complications. CONCLUSION: In properly
      selected patients, outpatient tubeless PCNL is safe and effective. Our initial
      experience with outpatient PCNL has been favourable and warrants further
      investigation in a larger patient population.

PMID- 20694091
TI  - Xanthogranulomatous cystitis associated with inflammatory bowel disease.
AB  - Xanthogranulomatous inflammation is a benign condition characterized by the
      presence of multinucleated giant cells, chronic inflammatory cells and lipid
      laden macrophages, known as xanthoma cells. Only 22 cases of xanthogranulomatous
      cystitis (XGC) have been reported in the Japanese and English literature. In this
      report, we describe the twenty-third case of XGC and the third case associated
      with inflammatory bowel disease (IBD). A 50-year-old woman with quiescent Crohn's
      disease was incidentally found to have a bladder mass on ultrasound. The lesion
      was resected through a transurethral approach. Pathology demonstrated XGC. At 3
      months post-resection, there was no evidence of recurrence adjacent to the
      previous resection scar.

PMID- 20694092
TI  - Atrophic upper pole of a duplex collecting system masquerading as suprarenal
      mass: a case study and literature review.
AB  - The growing use of maternal fetal ultrasound is leading to the discovery of an
      increasing number of suprarenal masses. Our experience with a cystic suprarenal
      mass detected on antenatal ultrasound is described. Location and radiographic
      features could not rule out the possibility of a cystic neuroblastoma; therefore,
      surgical resection of the mass was performed. Despite the absence of common
      radiologic characteristics, the pathology of the specimen revealed a non
      functioning upper pole of a duplex kidney with complete duplication of the
      collecting system. Neonatal evaluation and management and the differential
      diagnosis are discussed.

PMID- 20694093
TI  - Resection of a staggering 36-cm angiomyolipoma.
AB  - Angiomyolipomas (AMLs) are benign tumours characterized by fat, smooth muscle and
      vascular components. Epithelioid AML is a recognized variant of AML that is
      comprised of epithelioid smooth muscle cells. We present a case of a 41-year-old
      male who presented with light-headedness, dizziness, right-sided abdominal pain
      and, on subsequent computed tomography, was found to have an enormous right
      kidney mass characteristic of an AML. The patient underwent preoperative
      selective arterial embolization followed by a right radical nephrectomy. The
      pathology revealed a 36-cm AML with focal epithelioid features. Although
      uncommon, AMLs can present as enormous retroperitoneal masses.

PMID- 20694094
TI  - MRI and prostate cancer: the next frontier.

PMID- 20694095
TI  - Next year - Montreal!

PMID- 20694096
TI  - High-intensity focused ultrasound for prostate cancer: a practice guideline.
AB  - OBJECTIVE: The aim of this practice guideline was to develop evidence-based
      recommendations for clinicians on the use of high-intensity focused ultrasound
      (HIFU) in patients with localized prostate cancer. METHODS: The guideline was
      developed using the methods of Cancer Care Ontario's Program in Evidence-Based
      Care (PEBC). The core methodology of the PEBC's guideline development process is
      systematic review. A comprehensive literature search was undertaken to identify
      high-quality studies, reviews and other practice guidelines on the use of HIFU in
      prostate cancer. The evidence formed the basis of the recommendations, which were
      reviewed and amended where necessary, by clinical experts in medical and
      radiation oncology and urology. RESULTS: The literature review yielded limited
      evidence. No randomized controlled trials or meta-analyses comparing HIFU with
      currently accepted management approaches were identified. The body of evidence is
      primarily based on data from case series. Internal feedback was provided by the
      PEBC Genitourinary Disease Site Group membership and the Report Approval Panel.
      External peer review included targeted review by clinical experts specifically
      requested to comment on the guideline, and professional consultation through an
      online survey of health care professionals. CONCLUSION: HIFU is currently not
      recommended as an alternative to accepted curative treatment approaches for
      localized prostate cancer.

PMID- 20694097
TI  - A cost-analysis comparison of laparoscopic radical prostatectomy versus open
      radical prostatectomy: the McMaster Institute of Urology experience.
AB  - INTRODUCTION: The objective of this study was to identify and compare the costs
      of laparoscopic radical prostatectomy (LRP) and radical retropubic prostatectomy
      (RRP) at our centre. METHODS: We conducted a retrospective chart review of our
      first 70 consecutive LRP cases and 70 consecutive RRP cases at St. Joseph's
      Healthcare in Hamilton, Ontario, Canada. We performed cost analysis, including
      operating room costs, disposable instruments, blood transfusions, analgesic
      requirements and length of hospital stay. Overall expenses were then analyzed and
      compared. RESULTS: Preoperative patient demographics and disease stages were
      comparable between the LRP and RRP groups. On a per procedure basis, large
      discrepancies were found in mean disposable instrument costs (LRP = $659.18 vs.
      RRP = $236.59), operating room costs (LRP = $4278.00 vs. RRP = $3139.00), mean
      cost of blood transfusions (LRP = $21.00 vs. RRP = $394.34), mean analgesia
      requirements (LRP = $12.94 vs. RRP = $41.06) and mean hospital stay bed costs
      (LRP = $3690.00 vs. RRP = $5027.14). Overall, costs for all patients in the LRP
      and RRP groups, respectively, were $606 307.29 and $618 721.57 with a cost saving
      of $12 414.28 in favour of the LRP arm. CONCLUSION: At our institution, we found
      that LRP costs are slightly less than those for RRP. Higher operative time and
      disposable instrument expenses are offset by the shorter hospital stays, fewer
      blood transfusions and less analgesic requirements for the LRP group. Further
      financial advantages for LRP will likely be achieved with additional reduction of
      operating room time and by minimizing disposables.

PMID- 20694098
TI  - A cost analysis of radical prostatectomies: Will it ever be possible?

PMID- 20694099
TI  - Wait times in prostate cancer diagnosis and radiation treatment.
AB  - INTRODUCTION: Wait times for cancer diagnosis and treatment are a significant
      concern for Canadians. Men with prostate cancer experience longer waiting times
      for diagnosis and treatment than those observed for other cancers. Longer waits
      are associated with both patient and family psychosocial distress and may be
      associated with worse prognosis. METHODS: Men referred for treatment of prostate
      cancer at a single Canadian cancer centre were interviewed. The intervals from
      suspicion to definitive therapy were calculated, factors associated with delays
      along this pathway were identified, and common causes of delay identified by
      patients were described. RESULTS: A total of 41 consecutive patients
      participated. The median interval from suspicion to the first fraction of
      radiotherapy for all patients was 247 days (interquartile range [IQR] 168-367 d).
      The median diagnostic interval was 53 days (IQR 28-166 d). The median treatment
      interval was 127 days (IQR 100-180 d). Patients under 70 years old and patients
      with <T2c disease had shorter intervals from suspicion to treatment. From
      diagnosis to start of radiotherapy, patients with low-risk disease had longer
      intervals. Seventy percent of patients perceived a delay in their care, of which
      45%, 31% and 24% of patients felt the delays were due to the health care system,
      patient or physician factors, respectively. INTERPRETATION: In this study, 12%
      and 0% of patients met Canadian Strategy for Cancer Control and Canadian
      Association of Radiation Oncologists wait time recommendations, respectively. A
      large component of wait time is patient driven. Alternate strategies should be
      developed and measured to shorten the intervals between the suspicion and
      treatment of prostate cancer.

PMID- 20694100
TI  - Dealing with wait times in prostate cancer.

PMID- 20694101
TI  - Impact of body mass index on perioperative outcomes during the learning curve for
      robot-assisted radical prostatectomy.
AB  - INTRODUCTION: Previous studies of robotic-assisted radical prostatectomy (RARP)
      have suggested that obesity is a risk factor for worse perioperative outcomes. We
      evaluated whether body mass index (BMI) adversely affected perioperative
      outcomes. METHODS: A prospective database of 153 RARP (single surgeon) was
      analyzed. Obesity was defined as BMI >/= 30 kg/m(2); normal BMI < 25 kg/m(2); and
      overweight as 25 to 30 kg/m(2). Two separate analyses were performed: the first
      50 cases (the initial learning curve) and the entire cohort of 153 RARP. RESULTS:
      In the initial cohort of 50 cases (14 obese patients), there was no statistically
      significant difference with regards to operative times, port-placement times and
      estimated blood loss (EBL). Length of stay (LOS) was longer in the obese group
      (4.3 vs. 2.9 days); BMI remained an independent predictor of increased LOS on
      multivariate linear regression analysis (p = 0.002). There was no statistically
      significant difference in the postoperative outcomes of leak rates, margin rates
      and incisional herniae. In the entire cohort, when comparing obese patients to
      those with a normal BMI, there was no statistically significant difference in
      operative times, EBL, LOS, or immediate postoperative outcomes. However, on
      multivariate linear regression analysis, BMI was an independent predictor of
      increased operative time (p = 0.007). CONCLUSION: Obese patients do not have an
      increased risk of blood loss, positive margins or the postoperative complications
      of incisional hernia and leak during the learning curve. They do, however, have
      slightly longer operative times; we also noted an increased LOS in our first 50
      cases.

PMID- 20694102
TI  - Robotic surgery techniques for obese patients.

PMID- 20694103
TI  - Diagnostic accuracy of surface coil magnetic resonance imaging at 1.5 T for local
      staging of elevated risk prostate cancer.
AB  - INTRODUCTION: Preoperative prostate cancer stage predicts prognosis and affects
      treatment decisions. The purpose of this study was to estimate the sensitivity
      and specificity of surface coil magnetic resonance imaging (MRI) for prostate
      cancer stage using surgical pathologic data as the reference standard. METHODS:
      High-risk patients (>/=cT3 or PSA >/=20 ng/mL or Gleason >/=8) and selected
      intermediate-risk patients (clinically bulky disease on exam or biopsy, cT2b/c,
      or Gleason 7 with >/=3 of 5 biopsy cores positive in a lobe) routinely received a
      pelvic MRI at our institution. The images of identified patients were reviewed by
      one radiologist who was blinded to clinical information. The radiologist reported
      presence or absence of tumour within each lobe of the prostate. Extraprostatic
      extension (EPE), seminal vesicle (SV) invasion and pelvic lymph node (PLN)
      metastasis were also reported. Radiological findings were compared with
      prostatectomy pathology reports. RESULTS: During the study period, about 320
      radical prostatectomies were performed. Of these, 32 had a preoperative surface
      coil pelvic MRI adequate for analysis. Pathologically, 53 of 64 (82.8%) prostate
      lobes contained tumour, 17 (26.6%) lobes had associated EPE, 12 (18.8%) had SV
      involvement and 7 (10.9%) sets of PLNs contained cancer. Magnetic resonance
      imaging sensitivity and specificity were, respectively, 94.3% and 81.8% for
      tumour location, 82.4% and 87.2% for EPE, 83.3% and 92.3% for SV invasion and
      71.4% and 94.7% for PLN involvement. INTERPRETATION: Surface coil MRI accurately
      stages many prostate cancer patients with elevated risk of extraprostatic
      disease. This mode of imaging may be reasonable at centres that do not have
      endorectal coil MRI.

PMID- 20694105
TI  - Using clinical practice guidelines in our own backyard: treating our patients
      with bladder cancer.

PMID- 20694104
TI  - Referral and treatment rates of neoadjuvant chemotherapy in muscle-invasive
      bladder cancer before and after publication of a clinical practice guideline.
AB  - INTRODUCTION: The objective of this study was to compare referral and treatment
      rates of neoadjuvant chemotherapy for patients with muscle-invasive bladder
      cancer before and after publication of a clinical practice guideline. METHODS:
      This was a retrospective comparative cohort study of 236 patients diagnosed with
      clinical stage >/= T2 bladder cancer in Alberta, Canada. Patients were divided
      into 2 groups based on the time of diagnosis relative to the publication of the
      Alberta Genitourinary Oncology Group Clinical Practice Guideline on Bladder
      Cancer (CPG), which recommends cisplatin-based neoadjuvant chemotherapy for
      muscle-invasive disease. The pre-CPG group included patients (n = 129) diagnosed
      prior to publication of the CPG (November 1, 2002 to October 31, 2004,
      inclusively). The post-CPG group included patients (n = 107) diagnosed after
      publication of the CPG (November 1, 2005 to October 31, 2007). There was an
      accrual blackout period of 6 months before and after the CPG release date. The
      primary analysis compared the two groups with respect to neoadjuvant chemotherapy
      referral rates, treatment-offered rates and treatment-administered rates.
      RESULTS: Referral to medical oncology regarding neoadjuvant chemotherapy occurred
      in 2.3% and 23.4% of patients in the pre- and post-CPG groups, respectively (p <
      0.01). Neoadjuvant chemotherapy was offered to 0.8% and 18.7% of patients in the
      pre- and post-CPG groups, respectively (p < 0.01). Neoadjuvant chemotherapy was
      administered to 0.8% and 14.0% of patients in the pre- and post-CPG groups,
      respectively (p < 0.01). INTERPRETATION: Neoadjuvant referral and treatment rates
      increased after publication of the CPG. However, overall referral and treatment
      rates remained low, which warrants additional exploration.

PMID- 20694106
TI  - A practical guide to diagnosis, management and treatment of testosterone
      deficiency for Canadian physicians.
AB  - The percentage of men receiving appropriate management for testosterone
      deficiency syndrome (TDS) is small in comparison to prevalence estimates. This is
      despite linkages to cardiovascular disease, osteoporosis, diabetes, sexual
      function, sarcopenia, emotional well-being and the metabolic syndrome.
      Furthermore, the availability of guidelines has not significantly enhanced the
      care of TDS patients. A multidisciplinary group of medical experts sought to
      improve the management of testosterone-deficient patients by Canadian physicians.
      This report describes their conclusions and defines an algorithm for appropriate
      TDS management.

PMID- 20694108
TI  - Rebuttal.

PMID- 20694107
TI  - Medical versus surgical management for vesicoureteric reflux: the case for
      medical management.

PMID- 20694109
TI  - Learning from history or the rationale for considering surgical correction of
      vesicoureteral reflux.

PMID- 20694110
TI  - Rebuttal.

PMID- 20694111
TI  - The impact of body image on patient care.

PMID- 20694112
TI  - Cancer as a precipitating event.

PMID- 20694113
TI  - Beyond symptomatic improvement:assessing real-world outcomes in patients with
      major depressive disorder.
AB  - OBJECTIVE: To quantify the negative impact that major depressive disorder (MDD)
      has on quality of life, disability, and work, family, and overall psychosocial
      functioning. Available scales that assess these areas of impairment as they
      relate to patients with MDD are described. DATA SOURCES: PUBMED SEARCHES WERE
      CONDUCTED USING THE FOLLOWING TERMS: (MDD OR major depressive disorder) AND
      (absenteeism OR absente*); AND (quality of life OR QOL); AND (psychosocial
      function*); AND (presente* OR presenteeism); AND (health care cost* OR [health
      care] cost*); AND (health outcome*); AND (functional outcome*); AND (family
      life); AND (disabil* OR disability); AND (work function*); AND (unemployment OR
      unemploy*). The literature search was conducted in July 2008 and was restricted
      to English language articles. There were no limits set on the dates of the
      search. STUDY SELECTION: Two hundred twenty potential articles were identified.
      Among these studies, 48 presented primary data directly demonstrating the effect
      of MDD on quality of life, disability, and work, family, and overall psychosocial
      functioning. DATA EXTRACTION: Primary data were compiled from these studies and
      are summarily described. Available scales that assess quality of life,
      disability, and work, family, and overall psychosocial functioning are also
      described. DATA SYNTHESIS: MDD was found to be associated with significant
      disability and declines in functioning and quality of life. The Sheehan
      Disability Scale, the 36-item Short-Form Health Survey, and the Work Limitations
      Questionnaire were the most commonly used scales according to this review of the
      literature, but the majority of studies used direct and indirect disability
      measures, such as health care and other disability-related costs. CONCLUSIONS: In
      addition to assessing symptomatic outcomes, physicians should routinely assess
      their depressed patients on "real-world" outcomes. The development of a concise
      functional outcome measure specific to MDD is necessary for busy clinical
      practices.

PMID- 20694114
TI  - Management of generalized anxiety disorder in primary care: identifying the
      challenges and unmet needs.
AB  - BACKGROUND: Generalized anxiety disorder (GAD) is one of the most common
      psychiatric disorders in primary care, although it is often underrecognized and
      undertreated. GAD is chronic, disabling, and associated with other health
      problems. Treatment response is often unsatisfactory, but the clinical evidence
      base for new treatments has expanded substantially in the past decade and
      suggests a growing range of options for reducing the burden of GAD. The objective
      of this article was to review current literature on GAD and its management to
      provide an overview of the clinical importance of GAD in primary care and
      available treatments. DATA SOURCES: Recent studies (ie, over the past decade) on
      the epidemiology and treatment of GAD were identified by searching Medline using
      the term generalized anxiety disorder only and in combination with the terms
      epidemiology and treatment and for each drug class (benzodiazepines, azapirones,
      antidepressants, antihistamines, alpha-2-delta ligands, and antipsychotics) and
      for named drugs (buspirone, venlafaxine, duloxetine, fluoxetine, escitalopram,
      olanzapine, paroxetine, pregabalin, quetiapine, and risperidone in addition to
      psychological therapies and cognitive-behavioral therapy. The literature search
      was conducted in August 2008 for the period 1987-2009. STUDY SELECTION: Studies
      were included if judged to be relevant to a review of the epidemiology and
      management of GAD. Articles were excluded if they were not written in English or
      were published more than 10 years before the literature search was conducted. A
      few older studies were included for which more recent research evidence was not
      available. Recent national and international guidelines for the management of GAD
      were also reviewed. DATA EXTRACTION/SYNTHESIS: Most currently available
      interventions have similar overall efficacy, and treatment choices should reflect
      the situation of individual patients. Important unmet needs exist for treatments
      (1) that work rapidly, with (2) broad spectrum benefits, (3) that can improve
      rates of remission and well-being, (4) are devoid of risk for withdrawal
      symptoms, and (5) have few if any adverse interactions with other drugs.
      Additional needs include (6) safer drugs for the elderly, (7) safe and effective
      drugs for children with GAD, (8) further evaluation of psychotherapy, and (9)
      understanding the appropriate circumstances for, and optimal choices of, drug
      combination. CONCLUSION: While the development of novel treatments evolves,
      current management approaches can focus on improving identification and defining
      optimal use of available therapies for GAD.

PMID- 20694115
TI  - Impulse-control disorders in a college sample: results from the self-administered
      Minnesota Impulse Disorders Interview (MIDI).
AB  - OBJECTIVE: This study sought to examine the prevalence rates of and gender
      differences among impulse-control disorders in a college sample. METHOD: During
      the fall semester of 2006, 791 college students from 2 private colleges in the
      Midwest completed a self-administered, modified version of the Minnesota Impulse
      Disorders Interview to assess lifetime rates of DSM-IV-TR-diagnosed impulse
      control disorders. Participation was voluntary and anonymous. RESULTS: The mean
      age of the sample was 20.0 +/- 1.25 years, with females comprising 67.9% of the
      respondents. Of the individuals, 10.4% (n = 82) met criteria for at least 1
      lifetime impulse-control disorder. The most common disorders were
      trichotillomania (3.91%) and compulsive sexual behavior (3.66%). Kleptomania was
      the least common (0.38%). Males were significantly more likely to screen positive
      for pathological gambling (P = .003) and compulsive sexual behavior (P = .002).
      Females were more likely to have compulsive buying (P = .033). CONCLUSIONS:
      Impulse-control disorders appear to be common among college students. The high
      rates indicate that these disorders may be incipient during late adolescence and
      early adulthood and should be addressed prior to onset of clinical versions of
      the impulse-control disorder.

PMID- 20694116
TI  - What about telepsychiatry? A systematic review.
AB  - BACKGROUND: Mental illness has become a significant worldwide health issue in
      recent years. There is presently insufficient evidence to definitively determine
      the clinical effectiveness and cost-effectiveness of different health care
      models. The objective of this study was to evaluate the effectiveness of
      videoconferencing in mental illness. DATA SOURCES: Literature searches were
      performed in Medline, EMBASE, PsycINFO, Centre for Reviews and Dissemination, and
      The Cochrane Library Controlled Trial Registry databases (1997-May 2008). A
      search of the following terms was used: e-health, mental disorders (MeSH term),
      mental health (MeSH term), mental health services (MeSH term), telecare,
      teleconsultation, telehome, telemedical, telemedicine, telemental,
      telepsychiatric, telepsychiatry, televideo, videoconference, and videophone.
      STUDY SELECTION: Type of disease, interventions, and clinical outcomes or patient
      satisfaction were identified. Exclusion criteria included studies that did not
      analyze intervention outcomes and studies with a sample size of fewer than 10
      cases. Peer review and quality assessment according to Cochrane recommendations
      were required for inclusion. DATA EXTRACTION/SYNTHESIS: Of 620 identified
      articles, 10 randomized controlled trials are included (1,054 patients with
      various mental disorders). There were no statistically significant differences
      between study groups for symptoms, quality of life, and patient satisfaction.
      CONCLUSIONS: There is insufficient scientific evidence regarding the
      effectiveness of telepsychiatry in the management of mental illness, and more
      research is needed to further evaluate its efficiency. However, there is a strong
      hypothesis that videoconference-based treatment obtains the same results as face
      to-face therapy and that telepsychiatry is a useful alternative when face-to-face
      therapy is not possible.

PMID- 20694117
TI  - Hospital admission for schizophrenia and discharge against medical advice in the
      United States.
AB  - OBJECTIVE: Hospital discharge against medical advice may leave a patient at risk
      for adverse health outcomes and/or readmission, yet little is known regarding its
      occurrence, especially among patients with mental illness. The objective of this
      study was to discern the prevalence of, and predictive factors for, being
      discharged against medical advice among hospitalized patients with a primary
      diagnosis of schizophrenia. METHOD: The 2004 US Healthcare Cost and Utilization
      Project Nationwide Inpatient Sample was used to discern demographic predictors,
      length of stay, and costs for discharge against medical advice relative to
      discharge with medical approval. Inpatient discharges from US community hospitals
      for patients of all ages with The International Classification of Diseases, 9th
      Revision, Clinical Modification diagnostic codes 295.0-295.9 were included.
      Conditional logistic regression was used to discern factors predictive of
      discharge against medical advice, and least squares mean analysis was used to
      examine differences in length of stay and mean cost per day relative to discharge
      with medical approval. Least squares means were adjusted for age (continuous),
      sex, race, region, payer, hospital setting, and bed size. RESULTS: Within the
      study population, 1.6% of patients admitted for schizophrenia were discharged
      against medical advice (n = 3,382/210,722). Patients discharged against medical
      advice were significantly more likely to be younger (OR = 0.985, 95% CI, 0.982
      0.987) and male (OR = 1.421, 95% CI, 1.321-1.529). Race was not a significant
      factor. Mean +/- SE length of stay for discharge against medical advice was 5.0
      +/- 0.24 days, as compared to 8.7 +/- 0.06 days for patients discharged with
      medical approval (P < .0001). Mean cost per day was significantly higher for
      discharge against medical advice ($1,886.02 +/- 49.67 vs $1,565.79 +/- 13.42, P <
      .0001). CONCLUSIONS: Although the percentage of patients discharged against
      medical advice was small, the numeric magnitude on a nationwide basis was
      substantial. The adjusted mean length of stay for discharge against medical
      advice was significantly reduced, while cost per day was significantly higher.
      Discharge against medical advice represents a challenge to the provision of care
      for patients with schizophrenia and may contribute to increased use of primary
      and specialty outpatient services, rehospitalization rates, morbidity, and
      mortality.

PMID- 20694118
TI  - Burden of chronic sleep maintenance insomnia characterized by nighttime
      awakenings among anxiety and depression sufferers: results of a national survey.
AB  - OBJECTIVE: To identify and quantify the burden of chronic sleep maintenance
      insomnia characterized by nighttime awakenings (CINA) among depression and
      anxiety sufferers. METHOD: Data were obtained from the 2006 US National Health
      and Wellness Survey, an annual cross-sectional study of US adults. Analyses were
      limited to respondents diagnosed with depression or anxiety. The term CINA was
      defined as experiencing nighttime awakenings, without difficulty falling asleep,
      at least twice per week for more than 1 month that have moderate-severe impact on
      daily life. Outcomes included resource utilization in past 6 months, the Work
      Productivity and Activity Impairment questionnaire, and the Medical Outcomes
      Study 8-item Short-Form Health Survey (SF-8). Independent effects of CINA on
      outcomes adjusting for demographics and comorbidity were assessed using linear
      regression models. RESULTS: Among depression sufferers, 643 experienced CINA and
      1,675 experienced no insomnia. Among anxiety sufferers, 476 experienced CINA and
      1,356 experienced no insomnia. Adjusting for demographics and comorbidity,
      depression sufferers with CINA had 2.4 more provider visits, 13.2% greater work
      impairment (among full-time employed), 18.2% greater activity impairment, and SF
      8 physical and mental summary scores that were 4.8 and 6.7 points lower than
      noninsomnia sufferers (P < .001 for all). Anxiety sufferers with CINA had 3.0
      more provider visits, 15.8% greater work impairment (among full-time employed),
      20.4% greater activity impairment, and SF-8 physical and mental summary scores
      that were 5.4 and 7.6 points lower than noninsomnia sufferers (P < .001 for all).
      CONCLUSIONS: Among depression and anxiety sufferers, CINA in relative isolation
      was associated with a significant negative impact on health care utilization and
      its associated costs, health-related quality of life, and work productivity.

PMID- 20694119
TI  - Prevalence and correlates of clinically significant depressive symptoms in an
      urban hospital emergency department.
AB  - BACKGROUND: In hospital settings, depression is an underdetected, undertreated,
      but prevalent and interfering illness that is associated with significant
      disability, morbidity, and mortality. A general hospital emergency department
      (ED) setting may be well suited to identify individuals with clinically
      significant depressive symptoms, facilitating their referral and treatment.
      METHOD: Cross-sectional data of adult ED patients in a general hospital enrolling
      in a human immunodeficiency virus (HIV) screening study between February 2007 and
      March 2008 were analyzed. Data included demographic factors, the Center for
      Epidemiologic Studies Depression Scale (CES-D), alcohol and substance use
      history, sexual risk taking, and brief medical history. The primary outcome was a
      dichotomous measure of self-reported clinically significant depressive symptoms.
      Patients who scored >/= 16 on the CES-D were considered to screen positive for
      depressive symptoms. RESULTS: Of the 3,262 patients enrolled in the screening
      trial, 2,588 (79%) completed the survey between February 2007 and March 2008.
      Among these, 1,945 (75%) completed the psychosocial assessment battery; 596 (31%)
      survey completers screened positive for clinically significant depressive
      symptoms. In a multivariable model, female sex (RR = 1.36; 95% CI, 1.16-1.57),
      being unemployed (RR = 1.61; 95% CI, 1.32-1.93), and lower annual income (RR from
      1.73 to 2.24) were associated with increased rates of clinically significant
      depressive symptoms (CES-D score >/= 16). Clinically significant depressive
      symptoms were more often present in patients who screened positive for alcohol
      dependence (RR = 1.48; 95% CI, 1.19-1.78), individuals reporting current smoking
      (RR = 1.39; 95% CI, 1.17-1.62), those with a prior psychiatric disorder diagnosis
      (RR = 2.20; 95% CI, 1.80-2.57) or history of hypertension (RR = 1.47; 95% CI,
      1.18-1.79), and those who reported ever having sex with an HIV-infected partner
      (RR = 1.58; 95% CI, 1.08-2.09). CONCLUSIONS: This study identified a high
      frequency of undiagnosed clinically significant depressive symptoms among ED
      patients and highlights several new demographic and clinical correlates of such
      symptoms. Screening for and diagnosis of clinical depression in the ED setting
      introduces important opportunities for acute care providers and for the health
      care system as a whole.

PMID- 20694120
TI  - The effect of antipsychotic medication on neuromotor abnormalities in neuroleptic
      naive nonaffective psychotic patients: a naturalistic study with haloperidol,
      risperidone, or olanzapine.
AB  - OBJECTIVE: To examine the effect of antipsychotic medication on neuromotor
      abnormalities in a sample of psychotic patients never exposed to antipsychotic
      drugs. METHOD: One hundred psychotic patients were assessed (from January 1998 to
      December 2002) using DSM-IV criteria for parkinsonism, dyskinesia, akathisia,
      catatonia, and dystonia at baseline and after 4 weeks of treatment with
      haloperidol (n = 23), risperidone (n = 52), or olanzapine (n = 25). We examined
      change scores in neuromotor ratings over the treatment period across treatment
      groups and rates of drug-responsive and drug-emergent neuromotor syndromes in
      patients with and without preexisting neuromotor abnormalities. RESULTS: Overall
      time effects revealed a worsening of parkinsonism (P = .002) and akathisia (P =
      .002) ratings and an improvement of dyskinesia (P = .001) and catatonia (P <
      .001) ratings. Main treatment effects revealed that patients taking haloperidol
      had a significant mean increase in akathisia scores compared with those of
      patients taking risperidone (P = .002) or olanzapine (P < .001). A significantly
      greater percentage of olanzapine-treated patients experienced remission of
      preexisting parkinsonism than did the other treatment groups (P = .047). Patients
      without preexisting motor abnormalities were more likely to experience drug
      emergent parkinsonism if they were treated with haloperidol or risperidone than
      with olanzapine (P = .001) and were more likely to experience drug-emergent
      dystonia (P = .014) and akathisia (P = .013) if they were treated with
      haloperidol than with risperidone or olanzapine. CONCLUSIONS: The relationship
      between antipsychotic medication and neurologic abnormalities is more complex
      than previously acknowledged since antipsychotic drugs may both improve
      preexisting abnormalities and cause "de novo" neurologic syndromes. Overall,
      olanzapine has a more favorable neuromotor profile than risperidone, which in
      turn has a more favorable profile than haloperidol.

PMID- 20694121
TI  - Quetiapine treatment for delirious mania in a military soldier.

PMID- 20694122
TI  - An open-label trial of topiramate in the treatment of skin picking in pervasive
      developmental disorder not otherwise specified.

PMID- 20694123
TI  - Suicidal risk in a patient receiving tamoxifen treatment for breast cancer.

PMID- 20694124
TI  - Penile amputation after trazodone-induced priapism: a case report.

PMID- 20694125
TI  - Self-harm behaviors among buprenorphine-treated patients.

PMID- 20694126
TI  - Duloxetine may improve some symptoms of attention-deficit/hyperactivity disorder.

PMID- 20694127
TI  - Adjuvant metformin worsens psychosis in schizophrenia: a case report.

PMID- 20694128
TI  - Addition of bupropion SR to varenicline alleviated depression and suicidal
      ideation: a case report.

PMID- 20694129
TI  - Narcolepsy presenting as pseudoseizures.

PMID- 20694130
TI  - Comorbid bipolar disorder and Usher syndrome.

PMID- 20694134
TI  - Correlates of daytime sleepiness in patients with posttraumatic stress disorder
      and sleep disturbance.
AB  - OBJECTIVE: To assess the correlates of daytime sleepiness in patients with a
      lifetime diagnosis of posttraumatic stress disorder (PTSD) and ongoing sleep
      disturbance not due to sleep apnea or other diagnosed sleep disorders. METHOD:
      The sample consisted of 26 veterans receiving mental health care at the
      Minneapolis VA Medical Center, Minneapolis, Minnesota. The Epworth Sleepiness
      Scale was the primary outcome measure. Other sleep-related instruments consisted
      of the Pittsburgh Sleep Quality Scale, a daily sleep log, and daily sleep
      actigraphy. In addition, data included 3 symptom ratings (Posttraumatic Stress
      Disorder Checklist, Clinician Administered PTSD Scale [CAPS], and Beck Depression
      Inventory). Data were collected from 2003 to 2005. Current and lifetime PTSD
      diagnoses were based on DSM-IV criteria and were obtained by experienced
      psychiatrists using the CAPS interview. RESULTS: Univariate analyses showed that
      daytime sleepiness on the Epworth Sleepiness Scale was associated with daytime
      dysfunction on the Pittsburgh Sleep Quality Index (P < .001), less use of
      sleeping medication (P = .02), and more self-rated posttraumatic symptoms (P =
      .05). Within posttraumatic symptom categories, hypervigilance symptoms were more
      correlated with daytime sleepiness (P = .03) than were reexperiencing and
      avoidance symptoms (P = .09 for both). CONCLUSION: In this selected sample,
      daytime sleepiness was most strongly and independently associated with daytime
      dysfunction.

PMID- 20694135
TI  - Carbidopa/levodopa/entacapone: the evidence for its place in the treatment of
      Parkinson's disease.
AB  - INTRODUCTION: Parkinson's disease (PD) is a common neurodegenerative disease. In
      the 1960s, it was shown that the degeneration of dopamine producing neurons in
      the substantia nigra (SN) caused the motor features of PD. Dopamine replacement
      with levodopa, a dopamine precursor, resulted in remarkable benefit. Yet, the
      intermittent administration of levodopa is a major cause of motor complications,
      such as "wearing-off" of levodopa's benefit and involuntary movements, known as
      dyskinesia. Therefore, agents that prolong levodopa's half-life were employed,
      such as carbidopa, an aromatic amino acid decarboxylase (AADC) inhibitor, and
      entacapone, a catechol-O-methyltransferase (COMT) inhibitor. The combination
      product carbidopa/levodopa/entacapone (CLE) was approved in 2003 for the
      treatment of PD patients. AIMS: To assess the evidence for the place of CLE in
      the treatment of PD. EVIDENCE REVIEW: CLE has a good efficacy, safety and
      tolerability profile, similar to that of entacapone taken separately with
      carbidopa/levodopa (CL). Compared to CL alone, it prolongs levodopa's benefit,
      and improves the quality of life but not the motor performance in PD patients
      with nondebilitating "wearing-off" or dyskinesia. However, it increases the
      dyskinesia rate in early PD patients, and has adverse events in advanced patients
      with significant motor complications. There is insufficient evidence regarding
      cost-effectiveness. PLACE IN THERAPY: CLE is an attractive alternative for
      patients with nondisabling "wearing-off" or dyskinesia taking CL with or without
      entacapone. It cannot be recommended for early PD patients, as it can induce more
      dyskinesia than CL alone, or in any patients who seem to have more adverse
      events.

PMID- 20694136
TI  - Ustekinumab: an evidence-based review of its effectiveness in the treatment of
      psoriasis.
AB  - INTRODUCTION: Psoriasis is a chronic inflammatory skin disease affecting
      approximately 2% to 3% of the population worldwide. Discoveries over the past 3
      to 5 years have significantly altered our view of psoriasis as primarily a T-cell
      mediated condition. The most recent research has demonstrated the essential role
      of specific cytokines in the development of this complex disease, including TNF
      alpha, interleukin-23 (IL-23), and potentially, IL-22. These are all part of a
      newly defined autoimmune pathway directed by specialized T cells called Th17
      helper T cells. Ustekinumab is a fully human monoclonal antibody that targets IL
      12 and IL-23, thus targeting both Th1 and Th17 arms of immunity. It has a
      promising efficacy and safety profile that not only represents a valuable
      treatment alternative, but also a continuation in our constantly evolving
      understanding of this disorder. AIMS: To review the emerging evidence supporting
      the use of ustekinumab in the management of moderate to severe plaque psoriasis.
      EVIDENCE REVIEW: There is clear evidence that ustekinumab is effective in the
      treatment of moderate to severe psoriasis. Phase III trials (PHOENIX 1 and 2)
      demonstrated a statistically significant difference between Psoriasis Area and
      Severity Index (PASI) 75 responses achieved by patients receiving ustekinumab,
      given as a 45 mg or 90 mg subcutaneous injection every 12 weeks, than their
      placebo counterparts. Treatment with this novel agent resulted in a rapid onset
      of action, with over 60% of treated patients attaining Physician's Global
      Assessment (PGA) scores of "cleared" or "minimal" by week 12. Quality of life
      assessments paralleled clinical improvements. CLINICAL POTENTIAL: Ustekinumab is
      an effective and efficient therapeutic option for patients with moderate to
      severe psoriasis. Although further studies are required to establish
      ustekinumab's place in the therapy of psoriasis, with its convenient dosing
      schedule and rapid onset of action, this drug could provide a great addition to
      the current therapeutic armamentarium available for psoriatic patients.

PMID- 20694137
TI  - Optical imaging of retinotopic maps in a small songbird, the zebra finch.
AB  - BACKGROUND: The primary visual cortex of mammals is characterised by a
      retinotopic representation of the visual field. It has therefore been speculated
      that the visual wulst, the avian homologue of the visual cortex, also contains
      such a retinotopic map. We examined this for the first time by optical imaging of
      intrinsic signals in zebra finches, a small songbird with laterally placed eyes.
      In addition to the visual wulst, we visualised the retinotopic map of the optic
      tectum which is homologue to the superior colliculus in mammals.
      METHODOLOGY/PRINCIPAL FINDINGS: For the optic tectum, our results confirmed
      previous accounts of topography based on anatomical studies and conventional
      electrophysiology. Within the visual wulst, the retinotopy revealed by our
      experiments has not been illustrated convincingly before. The frontal part of the
      visual field (0 degrees +/-30 degrees azimuth) was not represented in the
      retinotopic map. The visual field from 30 degrees -60 degrees azimuth showed
      stronger magnification compared with more lateral regions. Only stimuli within
      elevations between about 20 degrees and 40 degrees above the horizon elicited
      neuronal activation. Activation from other elevations was masked by activation of
      the preferred region. Most interestingly, we observed more than one retinotopic
      representation of visual space within the visual wulst, which indicates that the
      avian wulst, like the visual cortex in mammals, may show some compartmentation
      parallel to the surface in addition to its layered structure.
      CONCLUSION/SIGNIFICANCE: Our results show the applicability of the optical
      imaging method also for small songbirds. We obtained a more detailed picture of
      retinotopic maps in birds, especially on the functional neuronal organisation of
      the visual wulst. Our findings support the notion of homology of visual wulst and
      visual cortex by showing that there is a functional correspondence between the
      two areas but also raise questions based on considerable differences between
      avian and mammalian retinotopic representations.

PMID- 20694138
TI  - Virtual screening for HIV protease inhibitors: a comparison of AutoDock 4 and
      Vina.
AB  - BACKGROUND: The AutoDock family of software has been widely used in protein
      ligand docking research. This study compares AutoDock 4 and AutoDock Vina in the
      context of virtual screening by using these programs to select compounds active
      against HIV protease. METHODOLOGY/PRINCIPAL FINDINGS: Both programs were used to
      rank the members of two chemical libraries, each containing experimentally
      verified binders to HIV protease. In the case of the NCI Diversity Set II, both
      AutoDock 4 and Vina were able to select active compounds significantly better
      than random (AUC = 0.69 and 0.68, respectively; p<0.001). The binding energy
      predictions were highly correlated in this case, with r = 0.63 and iota = 0.82.
      For a set of larger, more flexible compounds from the Directory of Universal
      Decoys, the binding energy predictions were not correlated, and only Vina was
      able to rank compounds significantly better than random.
      CONCLUSIONS/SIGNIFICANCE: In ranking smaller molecules with few rotatable bonds,
      AutoDock 4 and Vina were equally capable, though both exhibited a size-related
      bias in scoring. However, as Vina executes more quickly and is able to more
      accurately rank larger molecules, researchers should look to it first when
      undertaking a virtual screen.

PMID- 20694139
TI  - Effects of wolves on elk and cattle behaviors: implications for livestock
      production and wolf conservation.
AB  - BACKGROUND: In many areas, livestock are grazed within wolf (Canis lupus) range.
      Predation and harassment of livestock by wolves creates conflict and is a
      significant challenge for wolf conservation. Wild prey, such as elk (Cervus
      elaphus), perform anti-predator behaviors. Artificial selection of cattle (Bos
      taurus) might have resulted in attenuation or absence of anti-predator responses,
      or in erratic and inconsistent responses. Regardless, such responses might have
      implications on stress and fitness. METHODOLOGY/PRINCIPAL FINDINGS: We compared
      elk and cattle anti-predator responses to wolves in southwest Alberta, Canada
      within home ranges and livestock pastures, respectively. We deployed satellite-
      and GPS-telemetry collars on wolves, elk, and cattle (n = 16, 10 and 78,
      respectively) and measured seven prey response variables during periods of wolf
      presence and absence (speed, path sinuosity, time spent head-up, distance to
      neighboring animals, terrain ruggedness, slope and distance to forest). During
      independent periods of wolf presence (n = 72), individual elk increased path
      sinuosity (Z = -2.720, P = 0.007) and used more rugged terrain (Z = -2.856, P =
      0.004) and steeper slopes (Z = -3.065, P = 0.002). For cattle, individual as well
      as group behavioral analyses were feasible and these indicated increased path
      sinuosity (Z = -2.720, P = 0.007) and decreased distance to neighbors (Z = 
      2.551, P = 0.011). In addition, cattle groups showed a number of behavioral
      changes concomitant to wolf visits, with variable direction in changes.
      CONCLUSIONS/SIGNIFICANCE: Our results suggest both elk and cattle modify their
      behavior in relation to wolf presence, with potential energetic costs. Our study
      does not allow evaluating the efficacy of anti-predator behaviors, but indicates
      that artificial selection did not result in their absence in cattle. The costs of
      wolf predation on livestock are often compensated considering just the market
      value of the animal killed. However, society might consider refunding some
      additional costs (e.g., weight loss and reduced reproduction) that might be
      associated with the changes in cattle behaviors that we documented.

PMID- 20694140
TI  - Evolutionary origin and phylogeography of the diploid obligate parthenogen
      Artemia parthenogenetica (Branchiopoda: Anostraca).
AB  - BACKGROUND: Understanding the evolutionary origin and the phylogeographic
      patterns of asexual taxa can shed light on the origin and maintenance of sexual
      reproduction. We assessed the geographic origin, genetic diversity, and
      phylogeographic history of obligate parthenogen diploid Artemia parthenogenetica
      populations, a widespread halophilic crustacean. METHODOLOGY/PRINCIPAL FINDINGS:
      We analysed a partial sequence of the Cytochrome c Oxidase Subunit I
      mitochondrial gene from an extensive set of localities (including Eurasia,
      Africa, and Australia), and examined their phylogeographic patterns and the
      phylogenetic relationships of diploid A. parthenogenetica and its closest sexual
      relatives. Populations displayed an extremely low level of mitochondrial genetic
      diversity, with one widespread haplotype shared by over 79% of individuals
      analysed. Phylogenetic and phylogeographic analyses indicated a multiple and
      recent evolutionary origin of diploid A. parthenogenetica, and strongly suggested
      that the geographic origin of parthenogenesis in Artemia was in Central Asia. Our
      results indicate that the maternal sexual ancestors of diploid A.
      parthenogenetica were an undescribed species from Kazakhstan and A. urmiana.
      CONCLUSIONS/SIGNIFICANCE: We found evidence for multiple origin of
      parthenogenesis in Central Asia. Our results indicated that, shortly after its
      origin, diploid A. parthenogenetica populations underwent a rapid range expansion
      from Central Asia towards the Mediterranean region, and probably to the rest of
      its current geographic distribution. This contrasts with the restricted
      geographic distribution, strong genetic structure, and regional endemism of
      sexual Artemia lineages and other passively dispersed sexual continental aquatic
      invertebrates. We hypothesize that diploid parthenogens might have reached their
      current distribution in historical times, with a range expansion possibly
      facilitated by an increased availability of suitable habitat provided by
      anthropogenic activities, such as the spread of solar saltworks, aided by their
      natural dispersal vectors (i.e., waterbirds).

PMID- 20694141
TI  - Long-term survival of an urban fruit bat seropositive for Ebola and Lagos bat
      viruses.
AB  - Ebolaviruses (EBOV) (family Filoviridae) cause viral hemorrhagic fevers in humans
      and non-human primates when they spill over from their wildlife reservoir hosts
      with case fatality rates of up to 90%. Fruit bats may act as reservoirs of the
      Filoviridae. The migratory fruit bat, Eidolon helvum, is common across sub
      Saharan Africa and lives in large colonies, often situated in cities. We screened
      sera from 262 E. helvum using indirect fluorescent tests for antibodies against
      EBOV subtype Zaire. We detected a seropositive bat from Accra, Ghana, and
      confirmed this using western blot analysis. The bat was also seropositive for
      Lagos bat virus, a Lyssavirus, by virus neutralization test. The bat was fitted
      with a radio transmitter and was last detected in Accra 13 months after release
      post-sampling, demonstrating long-term survival. Antibodies to filoviruses have
      not been previously demonstrated in E. helvum. Radio-telemetry data demonstrates
      long-term survival of an individual bat following exposure to viruses of families
      that can be highly pathogenic to other mammal species. Because E. helvum
      typically lives in large urban colonies and is a source of bushmeat in some
      regions, further studies should determine if this species forms a reservoir for
      EBOV from which spillover infections into the human population may occur.

PMID- 20694142
TI  - Characterization of substrate preference for Slc1p and Cst26p in Saccharomyces
      cerevisiae using lipidomic approaches and an LPAAT activity assay.
AB  - BACKGROUND: Phosphatidic acid (PA) is a key regulated intermediate and precursor
      for de novo biosynthesis of all glycerophospholipids. PA can be synthesized
      through the acylation of lysophosphatidic acid (LPA) by 1-acyl-3-phosphate
      acyltransferase (also called lysophosphatidic acid acyltransferase, LPAAT).
      Recent findings have substantiated the essential roles of acyltransferases in
      various biological functions. METHODOLOGIES/PRINCIPAL FINDINGS: We used a flow
      injection-based lipidomic approach with approximately 200 multiple reaction
      monitoring (MRM) transitions to pre-screen fatty acyl composition of
      phospholipids in the yeast Saccharomyces cerevisiae mutants. Dramatic changes
      were observed in fatty acyl composition in some yeast mutants including Slc1p, a
      well-characterized LPAAT, and Cst26p, a recently characterized
      phosphatidylinositol stearoyl incorporating 1 protein and putative LPAAT in S.
      cerevisiae. A comprehensive high-performance liquid chromatography-based multi
      stage MRM approach (more than 500 MRM transitions) was developed and further
      applied to quantify individual phospholipids in both strains to confirm these
      changes. Our data suggest potential fatty acyl substrates as well as fatty acyls
      that compensate for defects in both Cst26p and Slc1p mutants. These results were
      consistent with those from a non-radioactive LPAAT enzymatic assay using C17-LPA
      and acyl-CoA donors as substrates. CONCLUSIONS: We found that Slc1p utilized
      fatty acid (FA) 18:1 and FA 14:0 as substrates to synthesize corresponding PAs;
      moreover, it was probably the only acyltransferase responsible for acylation of
      saturated short-chain fatty acyls (12:0 and 10:0) in S. cerevisiae. We also
      identified FA 18:0, FA 16:0, FA 14:0 and exogenous FA 17:0 as preferred
      substrates for Cst26p because transformation with a GFP-tagged CST26 restored the
      phospholipid profile of a CST26 mutant. Our current findings expand the enzymes
      and existing scope of acyl-CoA donors for glycerophospholipid biosynthesis.

PMID- 20694143
TI  - Inhibition of the soluble epoxide hydrolase promotes albuminuria in mice with
      progressive renal disease.
AB  - Epoxyeicotrienoic acids (EETs) are cytochrome P450-dependent anti-hypertensive
      and anti-inflammatory derivatives of arachidonic acid, which are highly abundant
      in the kidney and considered reno-protective. EETs are degraded by the enzyme
      soluble epoxide hydrolase (sEH) and sEH inhibitors are considered treatment for
      chronic renal failure (CRF). We determined whether sEH inhibition attenuates the
      progression of CRF in the 5/6-nephrectomy model (5/6-Nx) in mice. 5/6-Nx mice
      were treated with a placebo, an ACE-inhibitor (Ramipril, 40 mg/kg), the sEH
      inhibitor cAUCB or the CYP-inhibitor fenbendazole for 8 weeks. 5/6-Nx induced
      hypertension, albuminuria, glomerulosclerosis and tubulo-interstitial damage and
      these effects were attenuated by Ramipril. In contrast, cAUCB failed to lower the
      blood pressure and albuminuria was more severe as compared to placebo. Plasma EET
      levels were doubled in 5/6 Nx-mice as compared to sham mice receiving placebo.
      Renal sEH expression was attenuated in 5/6-Nx mice but cAUCB in these animals
      still further increased the EET-level. cAUCB also increased 5-HETE and 15-HETE,
      which derive from peroxidation or lipoxygenases. Similar to cAUCB, CYP450
      inhibition increased HETEs and promoted albuminuria. Thus, sEH-inhibition failed
      to elicit protective effects in the 5/6-Nx model and showed a tendency to
      aggravate the disease. These effects might be consequence of a shift of
      arachidonic acid metabolism into the lipoxygenase pathway.

PMID- 20694144
TI  - Monkey steering responses reveal rapid visual-motor feedback.
AB  - The neural mechanisms underlying primate locomotion are largely unknown. While
      behavioral and theoretical work has provided a number of ideas of how navigation
      is controlled, progress will require direct physiolgical tests of the underlying
      mechanisms. In turn, this will require development of appropriate animal models.
      We trained three monkeys to track a moving visual target in a simple virtual
      environment, using a joystick to control their direction. The monkeys learned to
      quickly and accurately turn to the target, and their steering behavior was quite
      stereotyped and reliable. Monkeys typically responded to abrupt steps of target
      direction with a biphasic steering movement, exhibiting modest but transient
      overshoot. Response latencies averaged approximately 300 ms, and monkeys were
      typically back on target after about 1 s. We also exploited the variability of
      responses about the mean to explore the time-course of correlation between target
      direction and steering response. This analysis revealed a broad peak of
      correlation spanning approximately 400 ms in the recent past, during which
      steering errors provoke a compensatory response. This suggests a continuous,
      visual-motor loop controls steering behavior, even during the epoch surrounding
      transient inputs. Many results from the human literature also suggest that
      steering is controlled by such a closed loop. The similarity of our results to
      those in humans suggests the monkey is a very good animal model for human
      visually guided steering.

PMID- 20694145
TI  - Control of cerebellar long-term potentiation by P-Rex-family guanine-nucleotide
      exchange factors and phosphoinositide 3-kinase.
AB  - BACKGROUND: Long-term potentiation (LTP) at the parallel fibre-Purkinje cell
      synapse in the cerebellum is a recently described and poorly characterized form
      of synaptic plasticity. The induction mechanism for LTP at this synapse is
      considered reciprocal to "classical" LTP at hippocampal CA1 pyramidal neurons:
      kinases promote increased trafficking of AMPA receptors into the postsynaptic
      density in the hippocampus, whereas phosphatases decrease internalization of AMPA
      receptors in the cerebellum. In the hippocampus, LTP occurs in overlapping
      phases, with the transition from early to late phases requiring the consolidation
      of initial induction processes by structural re-arrangements at the synapse. Many
      signalling pathways have been implicated in this process, including PI3 kinases
      and Rho GTPases. PRINCIPAL FINDINGS: We hypothesized that analogous phases are
      present in cerebellar LTP, and took as the starting point for investigation our
      recent discovery that P-Rex--a Rac guanine nucleotide exchange factor which is
      activated by PtdIns(3,4,5)P(3)--is highly expressed in mouse cerebellar Purkinje
      neurons and plays a role in motor coordination. We found that LTP evoked at
      parallel fibre synapses by 1 Hz stimulation or by NO donors was not sustained
      beyond 30 min when P-Rex was eliminated or Rac inhibited, suggesting that
      cerebellar LTP exhibits a late phase analogous to hippocampal LTP. In contrast,
      inhibition of PI3 kinase activity eliminated LTP at the induction stage.
      CONCLUSIONS: Our data suggest that a PI3K/P-Rex/Rac pathway is required for late
      phase LTP in the mouse cerebellum, and that other PI3K targets, which remain to
      be discovered, control LTP induction.

PMID- 20694146
TI  - Calpain 3 is a rapid-action, unidirectional proteolytic switch central to muscle
      remodeling.
AB  - Calpain 3 (CAPN3) is a cysteine protease that when mutated causes Limb Girdle
      Muscular Dystrophy 2A. It is thereby the only described Calpain family member
      that genetically causes a disease. Due to its inherent instability little is
      known of its substrates or its mechanism of activity and pathogenicity. In this
      investigation we define a primary sequence motif underlying CAPN3 substrate
      cleavage. This motif can transform non-related proteins into substrates, and
      identifies >300 new putative CAPN3 targets. Bioinformatic analyses of these
      targets demonstrate a critical role in muscle cytoskeletal remodeling and
      identify novel CAPN3 functions. Among the new CAPN3 substrates are three E3 SUMO
      ligases of the Protein Inhibitor of Activated Stats (PIAS) family. CAPN3 can
      cleave PIAS proteins and negatively regulates PIAS3 sumoylase activity.
      Consequently, SUMO2 is deregulated in patient muscle tissue. Our study thus
      uncovers unexpected crosstalk between CAPN3 proteolysis and protein sumoylation,
      with strong implications for muscle remodeling.

PMID- 20694147
TI  - ABO blood group and incidence of skin cancer.
AB  - BACKGROUND: Previous studies have examined the association between ABO blood
      group and the risk of some malignancies. However, no prospective cohort study to
      date has examined the association between ABO blood group and the risk of skin
      cancer. METHODOLOGY/PRINCIPAL FINDINGS: Using two large cohorts in the US, we
      examined ABO blood type and incidence of skin cancer, including melanoma,
      squamous cell carcinoma (SCC), and basal cell carcinoma (BCC). We followed up
      study participants (70,650 female nurses and 24,820 male health professionals) on
      their diagnosis of incident skin cancer from cohort baseline (1976 in women and
      1986 in men) until 2006. Study participants reported their blood type in 1996 in
      both cohorts. During the follow-up, 685 participants developed melanoma, 1,533
      developed SCC and 19,860 developed BCC. We used Cox proportional hazards models
      to calculate the hazard ratios (HR) and 95% confidence intervals (CI) of each
      type of skin cancer. We observed that non-O blood group (A, AB, and B combined)
      was significantly associated with a decreased risk of non-melanoma skin cancer
      overall. Compared to participants with blood group O, participants with non-O
      blood group had a 14% decreased risk of developing SCC (multivariable HR: 0.86;
      95% CI: 0.78, 0.95) and a 4% decreased risk of developing BCC (multivariable HR:
      0.96; 95% CI: 0.93, 0.99). The decreased risk of melanoma for non-O blood group
      was not statistically significant (multivariable HR: 0.91; 95% CI: 0.78, 1.05).
      CONCLUSION/SIGNIFICANCE: In two large independent populations, non-O blood group
      was associated with a decreased risk of skin cancer. The association was
      statistically significant for non-melanoma skin cancer. Additional studies are
      needed to confirm these associations and to define the mechanisms by which ABO
      blood type or closely linked genetic variants may influence skin cancer risk.

PMID- 20694148
TI  - A genome-wide association study of the metabolic syndrome in Indian Asian men.
AB  - We conducted a two-stage genome-wide association study to identify common genetic
      variation altering risk of the metabolic syndrome and related phenotypes in
      Indian Asian men, who have a high prevalence of these conditions. In Stage 1,
      approximately 317,000 single nucleotide polymorphisms were genotyped in 2700
      individuals, from which 1500 SNPs were selected to be genotyped in a further 2300
      individuals. Selection for inclusion in Stage 1 was based on four metabolic
      syndrome component traits: HDL-cholesterol, plasma glucose and Type 2 diabetes,
      abdominal obesity measured by waist to hip ratio, and diastolic blood pressure.
      Association was tested with these four traits and a composite metabolic syndrome
      phenotype. Four SNPs reaching significance level p<5x10(-7) and with posterior
      probability of association >0.8 were found in genes CETP and LPL, associated with
      HDL-cholesterol. These associations have already been reported in Indian Asians
      and in Europeans. Five additional loci harboured SNPs significant at p<10(-6) and
      posterior probability >0.5 for HDL-cholesterol, type 2 diabetes or diastolic
      blood pressure. Our results suggest that the primary genetic determinants of
      metabolic syndrome are the same in Indian Asians as in other populations, despite
      the higher prevalence. Further, we found little evidence of a common genetic
      basis for metabolic syndrome traits in our sample of Indian Asian men.

PMID- 20694149
TI  - A new acoustic portal into the odontocete ear and vibrational analysis of the
      tympanoperiotic complex.
AB  - Global concern over the possible deleterious effects of noise on marine organisms
      was catalyzed when toothed whales stranded and died in the presence of high
      intensity sound. The lack of knowledge about mechanisms of hearing in toothed
      whales prompted our group to study the anatomy and build a finite element model
      to simulate sound reception in odontocetes. The primary auditory pathway in
      toothed whales is an evolutionary novelty, compensating for the impedance
      mismatch experienced by whale ancestors as they moved from hearing in air to
      hearing in water. The mechanism by which high-frequency vibrations pass from the
      low density fats of the lower jaw into the dense bones of the auditory apparatus
      is a key to understanding odontocete hearing. Here we identify a new acoustic
      portal into the ear complex, the tympanoperiotic complex (TPC) and a plausible
      mechanism by which sound is transduced into the bony components. We reveal the
      intact anatomic geometry using CT scanning, and test functional preconceptions
      using finite element modeling and vibrational analysis. We show that the
      mandibular fat bodies bifurcate posteriorly, attaching to the TPC in two distinct
      locations. The smaller branch is an inconspicuous, previously undescribed
      channel, a cone-shaped fat body that fits into a thin-walled bony funnel just
      anterior to the sigmoid process of the TPC. The TPC also contains regions of thin
      translucent bone that define zones of differential flexibility, enabling the TPC
      to bend in response to sound pressure, thus providing a mechanism for vibrations
      to pass through the ossicular chain. The techniques used to discover the new
      acoustic portal in toothed whales, provide a means to decipher auditory
      filtering, beam formation, impedance matching, and transduction. These tools can
      also be used to address concerns about the potential deleterious effects of high
      intensity sound in a broad spectrum of marine organisms, from whales to fish.

PMID- 20694150
TI  - Copper-dependent trafficking of the Ctr4-Ctr5 copper transporting complex.
AB  - BACKGROUND: In Schizosaccharomyces pombe, copper uptake is carried out by a
      heteromeric complex formed by the Ctr4 and Ctr5 proteins. Copper-induced
      differential subcellular localization may play a critical role with respect to
      fine tuning the number of Ctr4 and Ctr5 molecules at the cell surface.
      METHODOLOGY/PRINCIPAL FINDINGS: We have developed a bimolecular fluorescence
      complementation (BiFC) assay to analyze protein-protein interactions in vivo in
      S. pombe. The assay is based on the observation that N- and C-terminal
      subfragments of the Venus fluorescent protein can reconstitute a functional
      fluorophore only when they are brought into tight contact. Wild-type copies of
      the ctr4(+) and ctr5(+) genes were inserted downstream of and in-frame with the
      nonfluorescent C-terminal (VC) and N-terminal (VN) coding fragments of Venus,
      respectively. Co-expression of Ctr4-VC and Ctr5-VN fusion proteins allowed their
      detection at the plasma membrane of copper-limited cells. Similarly, cells co
      expressing Ctr4-VN and Ctr4-VC in the presence of Ctr5-Myc(12) displayed a
      fluorescence signal at the plasma membrane. In contrast, Ctr5-VN and Ctr5-VC co
      expressed in the presence of Ctr4-Flag(2) failed to be visualized at the plasma
      membrane, suggesting a requirement for a combination of two Ctr4 molecules with
      one Ctr5 molecule. We found that plasma membrane-located Ctr4-VC-Ctr5-VN
      fluorescent complexes were internalized when the cells were exposed to high
      levels of copper. The copper-induced internalization of Ctr4-VC-Ctr5-VN complexes
      was not dependent on de novo protein synthesis. When cells were transferred back
      from high to low copper levels, there was reappearance of the BiFC fluorescent
      signal at the plasma membrane. SIGNIFICANCE: These findings reveal a copper
      dependent internalization and recycling of the heteromeric Ctr4-Ctr5 complex as a
      function of copper availability.

PMID- 20694151
TI  - Genome-wide analysis of effectors of peroxisome biogenesis.
AB  - Peroxisomes are intracellular organelles that house a number of diverse metabolic
      processes, notably those required for beta-oxidation of fatty acids. Peroxisomes
      biogenesis can be induced by the presence of peroxisome proliferators, including
      fatty acids, which activate complex cellular programs that underlie the induction
      process. Here, we used multi-parameter quantitative phenotype analyses of an
      arrayed mutant collection of yeast cells induced to proliferate peroxisomes, to
      establish a comprehensive inventory of genes required for peroxisome induction
      and function. The assays employed include growth in the presence of fatty acids,
      and confocal imaging and flow cytometry through the induction process. In
      addition to the classical phenotypes associated with loss of peroxisomal
      functions, these studies identified 169 genes required for robust signaling,
      transcription, normal peroxisomal development and morphologies, and transmission
      of peroxisomes to daughter cells. These gene products are localized throughout
      the cell, and many have indirect connections to peroxisome function. By
      integration with extant data sets, we present a total of 211 genes linked to
      peroxisome biogenesis and highlight the complex networks through which
      information flows during peroxisome biogenesis and function.

PMID- 20694153
TI  - Generalized Selectivity Description for Polymeric Ion-Selective Electrodes Based
      on the Phase Boundary Potential Model.
AB  - A generalized description of the response behavior of potentiometric polymer
      membrane ion-selective electrodes is presented on the basis of ion-exchange
      equilibrium considerations at the sample-membrane interface. This paper includes
      and extends on previously reported theoretical advances in a more compact yet
      more comprehensive form. Specifically, the phase boundary potential model is used
      to derive the origin of the Nernstian response behavior in a single expression,
      which is valid for a membrane containing any charge type and complex
      stoichiometry of ionophore and ion-exchanger. This forms the basis for a
      generalized expression of the selectivity coefficient, which may be used for the
      selectivity optimization of ion-selective membranes containing electrically
      charged and neutral ionophores of any desired stoichiometry. It is shown to
      reduce to expressions published previously for specialized cases, and may be
      effectively applied to problems relevant in modern potentiometry. The treatment
      is extended to mixed ion solutions, offering a comprehensive yet formally compact
      derivation of the response behavior of ion-selective electrodes to a mixture of
      ions of any desired charge. It is compared to predictions by the less accurate
      Nicolsky-Eisenman equation. The influence of ion fluxes or any form of
      electrochemical excitation is not considered here, but may be readily
      incorporated if an ion-exchange equilibrium at the interface may be assumed in
      these cases.

PMID- 20694152
TI  - Dynamics of Kv1 channel transport in axons.
AB  - Concerted actions of various ion channels that are precisely targeted along axons
      are crucial for action potential initiation and propagation, and neurotransmitter
      release. However, the dynamics of channel protein transport in axons remain
      unknown. Here, using time-lapse imaging, we found fluorescently tagged Kv1.2
      voltage-gated K(+) channels (YFP-Kv1.2) moved bi-directionally in discrete puncta
      along hippocampal axons. Expressing Kvbeta2, a Kv1 accessory subunit, markedly
      increased the velocity, the travel distance, and the percentage of moving time of
      these puncta in both anterograde and retrograde directions. Suppressing the
      Kvbeta2-associated protein, plus-end binding protein EB1 or kinesin II/KIF3A, by
      siRNA, significantly decreased the velocity of YFP-Kv1.2 moving puncta in both
      directions. Kvbeta2 mutants with disrupted either Kv1.2-Kvbeta2 binding or
      Kvbeta2-EB1 binding failed to increase the velocity of YFP-Kv1.2 puncta,
      confirming a central role of Kvbeta2. Furthermore, fluorescently tagged Kv1.2 and
      Kvbeta2 co-moved along axons. Surprisingly, when co-moving with Kv1.2 and
      Kvbeta2, EB1 appeared to travel markedly faster than its plus-end tracking.
      Finally, using fission yeast S. pombe expressing YFP-fusion proteins as reference
      standards to calibrate our microscope, we estimated the numbers of YFP-Kv1.2
      tetramers in axonal puncta. Taken together, our results suggest that proper
      amounts of Kv1 channels and their associated proteins are required for efficient
      transport of Kv1 channel proteins along axons.

PMID- 20694154
TI  - Joint Metabonomic and Instrumental Analysis for the Classification of Migraine
      Patients with 677-MTHFR Mutations.
AB  - Migraine is a neurological disorder that correlates with an increased risk of
      cerebrovascular lesions. Genetic mutations of the MTHFR gene are correlated to
      migraine and to the increased risk of artery pathologies. Also, migraine patients
      show altered hematochemical parameters, linked to an impaired platelet
      aggregation mechanism. Hence, the vascular assessment of migraineurs is of
      primary importance.Transcranial Doppler sonography (TCD) is used to measure
      cerebral blood flow velocity (CBFV) and vasomotor reactivity (by an index
      measured during breath-holding - BHI). Aim of this study was the metabolic
      profiling of migraine subjects with T/T677-MTHFR and C/T677-MTHFR mutations and
      its correlation with CBFV and BHI.Metabonomic multidimensional techniques were
      used to describe and cluster subjects. Fifty women suffering from migraine (age:
      18-64; 21 with aura) underwent TCD examination, hematochemical blood analysis,
      Born test, and genetic tests for MTHFR mutation. Fourteen (7 with aura) had
      T/T677, 18 (8 with aura) had C/T677, and 18 (6 with aura) had no mutation. The
      total number of variables was 24.Unsupervised and supervised techniques_showed
      the correlation between CBFV and BHI with mutation. Discriminant analysis allowed
      for classifying the subjects with 95.9% sensitivity and 89.0% specificity. Aura
      was not correlated to mutation or variations of instrumental data.Our study
      showed that metabonomics could be effectively applied in clinical problems to
      show the overall correlation structure of complex systems in pathology.
      Specifically, our results confirmed the importance of TCD in the metabolic
      profiling and follow-up of migraine patients.

PMID- 20694155
TI  - Finger motion classification by forearm skin surface vibration signals.
AB  - The development of prosthetic hand systems with both decoration and motion
      functionality for hand amputees has attracted wide research interests. Motion
      related myoelectric potentials measured from the surface of upper part of
      forearms were mostly employed to construct the interface between amputees and
      prosthesis.However, finger motions, which play a major role in dexterous hand
      activities, could not be recognized from surface EMG (Electromyogram) signals.The
      basic idea of this study is to use motion-related surface vibration, to detect
      independent finger motions without using EMG signals. In this research,
      accelerometers were used in a finger tapping experiment to collect the finger
      motion related mechanical vibration patterns. Since the basic properties of the
      signals are unknown, a norm based, a correlation coefficient based, and a power
      spectrum based method were applied to the signals for feature extraction. The
      extracted features were then fed to back-propagation neural networks to classify
      for different finger motions.The results showed that, the finger motion
      identification is possible by using the neural networks to recognize vibration
      patterns.

PMID- 20694156
TI  - Data mining techniques in medical informatics.

PMID- 20694157
TI  - Diagnosis of esophagitis based on face recognition techniques.
AB  - Face recognition technology has evolved over years with the Principal Component
      Analysis (PCA) method being the benchmark for recognition efficiency. The face
      recognition techniques take care of variation of illumination, pose and other
      features of the face in the image. We envisage an application of these face
      recognition techniques for classification of medical images. The motivating
      factor being, given a condition of an organ it is represented by some typical
      features. In this paper we report the use of the face recognition techniques to
      classify the type of Esophagitis, a condition of inflammation of the esophagus.
      The image of the esophagus is captured in the process of endoscopy. We test PCA,
      Fisher Face method and Independent Component Analysis techniques to classify the
      images of the esophagus. Esophagitis is classified into four categories. The
      results of classification for each method are reported and the results are
      compared.

PMID- 20694158
TI  - Region quad-tree decomposition based edge detection for medical images.
AB  - Edge detection in medical images has generated significant interest in the
      medical informatics community, especially in recent years. With the advent of
      imaging technology in biomedical and clinical domains, the growth in medical
      digital images has exceeded our capacity to analyze and store them for efficient
      representation and retrieval, especially for data mining applications. Medical
      decision support applications frequently demand the ability to identify and
      locate sharp discontinuities in an image for feature extraction and
      interpretation of image content, which can then be exploited for decision support
      analysis. However, due to the inherent high dimensional nature of the image
      content and the presence of ill-defined edges, edge detection using classical
      procedures is difficult, if not impossible, for sensitive and specific medical
      informatics-based discovery. In this paper, we propose a new edge detection
      technique based on the regional recursive hierarchical decomposition using
      quadtree and post-filtration of edges using a finite difference operator. We show
      that in medical images of common origin, focal and/or penumbral blurred edges can
      be characterized by an estimable intensity gradient. This gradient can further be
      used for dismissing false alarms. A detailed validation and comparison with
      related works on diabetic retinopathy images and CT scan images show that the
      proposed approach is efficient and accurate.

PMID- 20694159
TI  - Dynamic modelling of heart rate response under different exercise intensity.
AB  - Heart rate is one of the major indications of human cardiovascular response to
      exercises. This study investigates human heart rate response dynamics to moderate
      exercise. A healthy male subject has been asked to walk on a motorised treadmill
      under a predefined exercise protocol. ECG, body movements, and oxygen saturation
      (SpO2) have been reliably monitored and recorded by using non-invasive portable
      sensors. To reduce heart rate variation caused by the influence of various
      internal or external factors, the designed step response protocol has been
      repeated three times. Experimental results show that both steady state gain and
      time constant of heart rate response are not invariant when walking speed is
      faster than 3 miles/hour, and time constant of offset exercise is noticeably
      longer than that of onset exercise.

PMID- 20694161
TI  - Health Disparities and Discrimination: Three Perspectives.
AB  - This article presents three perspectives on health discrimination and
      disparities, organized around different conceptualizations of the way "space"
      perpetuates health disparities. The first two perspectives are grounded in
      conceptualizing space in a physical sense by exploring the manifestation of
      discrimination as a problem both among and within nations. The third perspective
      juxtaposes geographical space with cyberspace. The internet, with its ability to
      blur sense of place, social demarcations, and behavior is often considered a
      panacea that can eliminate the health disparities. The internet, however, may not
      be fulfilling its promise as an equal source of health information for all and
      disparities related to international and rural geography remain problematic.
      Solutions are proposed for reducing health disparities based on The Principle of
      Cultural Grounding (Hecht & Krieger, 2006; Hecht & Miller-Day, in press).

PMID- 20694160
TI  - Porcine skin-derived progenitor (SKP) spheres and neurospheres: Distinct
      "stemness" identified by microarray analysis.
AB  - Skin-derived progenitors (SKP) are neural crest derived and can generate neural
      and mesodermal progeny in vitro, corresponding to the multipotency of neural
      crest stem cells. Likewise, neural stem/progenitor cells (displaying as
      neurospheres) have the capacity of self-renewing, and can produce most phenotypes
      in the nervous system. Both form spheres when cultured with epidermal growth
      factor (EGF) and basic fibroblast growth factor (bFGF). Although the "stemness"
      of neural stem/progenitor cells has been extensively investigated, the molecular
      comparison of SKP spheres and neurospheres has not been elucidated. Here, SKP
      spheres and neurospheres from the same individual porcine fetuses were isolated
      with the same culture medium, and the multipotency was tested by in vitro
      differentiation assays. Microarray analysis was used to illustrate the "stemness"
      of SKP spheres and neurospheres. The upregulated genes that were in common in the
      SKP spheres and neurospheres are involved in ribosome, tight junction, gap
      junction, cell communication, calcium signaling, ErbB signaling, JAK-STAT
      signaling, MAPK signaling, etc. The differentially expressed genes between SKP
      spheres and neurospheres are mainly involved in ECM-receptor interaction and the
      transforming growth factor-beta (TGF-b) signaling pathway. Finally, treatment
      with leukemia inhibitory factor (LIF) or MEK inhibitor results in a distinctive
      impact on the "stemness" and differentiation genes of SKP spheres and
      neurospheres. Thus, the cell-intrinsic genetic program may contribute to the
      innate "stemness" of SKP spheres and neurospheres in a similar local
      microenvironment.

PMID- 20694163
TI  - QUANTITATIVE VALIDATION OF OPTICAL FLOW BASED MYOCARDIAL STRAIN MEASURES USING
      SONOMICROMETRY.
AB  - Dynamic cardiac metrics, including myocardial strains and displacements, provide
      a quantitative approach to evaluate cardiac function. However, in current
      clinical diagnosis, largely 2D strain measures are used despite the fact that
      cardiac motions are complex 3D volumes over time. Recent advances in 4D
      ultrasound enable the capability to capture such complex motion in a single image
      data set. In our previous work, a 4D optical flow based motion tracking algorithm
      was developed to extract fully 4D dynamic cardiac metrics from such 4D ultrasound
      data. In order to quantitatively evaluate our tracking method, in-vivo coronary
      artery occlusion experiments at various locations were performed on three canine
      hearts. Each dog was screened with 4D ultrasound and sonomicrometry data was
      acquired during each occlusion study. The 4D ultrasound data from these
      experiments was then analyzed with our tracking method and estimated principal
      strain measures were directly compared to those recorded by sonomicrometry, and
      showed strong agreement. This is the first validation study of optical flow based
      strain estimation for 4D ultrasound with direct comparison with sonomicrometry
      using in-vivo data.

PMID- 20694162
TI  - Prolylcarboxypeptidase (PRCP) as a new target for obesity treatment.
AB  - Recently, we serendipitously discovered that mice with the deficiency of the
      enzyme prolylcarboxypeptidase (PRCP) have elevated alpha-melanocyte-stimulating
      hormone (alpha-MSH) levels which lead to decreased food intake and weight loss.
      This suggests that PRCP is an endogenous inactivator of alpha-MSH and an appetite
      stimulant. Since a modest weight loss can have the most profound influence on
      reducing cardiovascular risk factors, the inhibitors of PRCP would be emerging as
      a possible alternative for pharmacotherapy in high-risk patients with obesity and
      obesity-related disorders. The discovery of a new biological activity of PRCP in
      the PRCP-deficient mice and studies of alpha-MSH function indicate the importance
      and complexity of the hypothalamic pro-opiomelanocortin (POMC) system in altering
      food intake. Identifying a role for PRCP in regulating alpha-MSH in the brain may
      be a critical step in enhancing our understanding of how the brain controls food
      intake and body weight. In light of recent findings, the potential role of PRCP
      in regulating fuel homeostasis is critically evaluated. Further studies of the
      role of PRCP in obesity are much needed.

PMID- 20694164
TI  - Multivariate Visual Explanation for High Dimensional Datasets.
AB  - Understanding multivariate relationships is an important task in multivariate
      data analysis. Unfortunately, existing multivariate visualization systems lose
      effectiveness when analyzing relationships among variables that span more than a
      few dimensions. We present a novel multivariate visual explanation approach that
      helps users interactively discover multivariate relationships among a large
      number of dimensions by integrating automatic numerical differentiation
      techniques and multidimensional visualization techniques. The result is an
      efficient workflow for multivariate analysis model construction, interactive
      dimension reduction, and multivariate knowledge discovery leveraging both
      automatic multivariate analysis and interactive multivariate data visual
      exploration. Case studies and a formal user study with a real dataset illustrate
      the effectiveness of this approach.

PMID- 20694165
TI  - Presurgical nasoalveolar molding for correction of cleft lip nasal deformity:
      experience from northern India.
AB  - CONTEXT: The cleft lip type nasal deformity presents one of the most complex
      surgical challenges. The long-term postoperative results are still not
      satisfactory despite an emphasis on primary nasal correction. This is attributed
      to tissue memory and healing. Nasoalveolar molding is used effectively to reshape
      the nasal cartilage and to mold the maxillary arch before cleft lip repair. AIMS:
      This study was undertaken to evaluate the role of presurgical nasoalveolar
      molding in correction of cleft lip nasal deformity for patients with unilateral
      and bilateral clefts of the lip. SETTINGS AND DESIGN: Twenty-three cases of
      clefts of lip and palate with nasal deformity were subjected to present study
      from May 2004 to May 2006. These cases were initially treated on outpatient
      basis, and they were admitted at the time of operation. All of these patients
      were children of less than 1 year of age, belonging to north Indian population.
      MATERIAL AND METHODS: Study consisted of patients of cleft lip and palate who
      were given presurgical nasoalveolar splints at early age. Lip repair was done
      after at least 2 months of molding. These patients along with control group
      (without presurgical nasoalveolar molding) were followed up for 1 year.
      Measurements were taken at different intervals in study over dental cast and on
      patients. Data obtained from comparison of 2 groups were analyzed using "MSTAT"
      analysis software (developed by Dr Russel Freed, Professor & Director, Crop &
      Soil Sciences Department, Michigan State University, East Lansing, Michigan).
      RESULTS: In our study, we found that nostril height was more in patients of
      experimental group (P = .18), while nostril width and alar perimeter were not
      changed significantly. Children with nasoalveolar molding had significant
      lengthening of columella (P = .02). Patients of unilateral cleft lip had more
      reduction in alveolar gap (P = .08) than bilateral group (P = .15). CONCLUSIONS:
      Nasoalveolar molding can be a useful adjunct for treatment of cleft lip nasal
      deformity. It is a cost-effective technique that can reduce the number of future
      surgeries such as alveolar bone grafting and secondary rhinoplasties.

PMID- 20694166
TI  - Autonomous magnetically actuated continuous flow microimmunofluorocytometry
      assay.
AB  - This article presents a microfluidic device which integrates autonomous serial
      immunofluorocytometry binding reactions of cytometric beads with fluorescence
      detection and quantification in a continuous flow environment. The microdevice
      assay is intended to alleviate the extensive benchwork and large sample volumes
      used when conducting traditional immunoassays, without requiring complex external
      controls. The technology is based on the miniaturization and automation of the
      serial processing steps of an antigen sandwich immunoassay, with integrated
      fluorescence detection using paramagnetic microbeads. The continuous flow design
      may enable temporal tracking of time-varying protein concentrations in a
      continuously infused sample for clinical applications, specifically for
      monitoring inflammation marker proteins in blood produced during cardiac
      surgeries involving cardiopulmonary bypass (CPB) procedures. The device operation
      was first validated via a single incubation device which measured the
      concentration of a fluorescently labeled biotin molecule using streptavidin
      coated paramagnetic cytometric beads. Subsequently, a dual incubation device was
      tested with samples of the anaphylatoxin complement protein C3a, and was shown to
      be capable of differentiating between samples at typical systemic concentrations
      of the protein (1-5 mug/ml), with very low sample usage (<6 mul/h). It is
      believed that this continuous flow, automated microimmunosensor technology will
      be a platform for high sample rate immunoassays capable of tracking and more
      thoroughly characterizing the systemic inflammation process, and may aid in the
      development of better treatment options for systemic inflammation during and
      after CPB.

PMID- 20694167
TI  - [carbonyl-C]Benzyl acetate: automated radiosynthesis via Pd-mediated [C]carbon
      monoxide chemistry and PET measurement of brain uptake in monkey.
AB  - [carbonyl-(11)C]Benzyl acetate ([(11)C]1) has been proposed as a potential agent
      for imaging glial metabolism of acetate to glutamate and glutamine with positron
      emission tomography (PET). [(11)C]1 was synthesized from [(11)C]carbon monoxide,
      iodomethane and benzyl alcohol via palladium-mediated chemistry. The
      radiosynthesis was automated with a modified Synthia platform controlled with in
      house developed Labview software. Under production conditions, [(11)C]1 was
      obtained in 10% (n = 6) decay-corrected radiochemical yield from [(11)C]carbon
      monoxide in > 96% radiochemical purity and with an average specific radioactivity
      of 2,415 mCi/micromol. The total radiosynthesis time was about 45 min. Peak
      uptake of radioactivity in brain (SUV = 3.1) was relatively high and may be
      amenable to measuring uptake and metabolism of acetate in glial cells of the
      brain.

PMID- 20694168
TI  - Item Selection, Evaluation, and Simple Structure in Personality Data.
AB  - We report an investigation of the genesis and interpretation of simple structure
      in personality data using two very different self-reported data sets. The first
      consists of a set of relatively unselected lexical descriptors, whereas the
      second is based on responses to a carefully constructed instrument. In both data
      sets, we explore the degree of simple structure by comparing factor solutions to
      solutions from simulated data constructed to have either strong or weak simple
      structure. The analysis demonstrates that there is little evidence of simple
      structure in the unselected items, and a moderate degree among the selected
      items. In both instruments, however, much of the simple structure that could be
      observed originated in a strong dimension of positive vs. negative evaluation.

PMID- 20694169
TI  - Development of Safe and Scalable Continuous-Flow Methods for Palladium-Catalyzed
      Aerobic Oxidation Reactions.
AB  - The synthetic scope and utility of Pd-catalyzed aerobic oxidation reactions has
      advanced significantly over the past decade, and these reactions have potential
      to address important green-chemistry challenges in the pharmaceutical industry.
      This potential has been unrealized, however, because safety concerns and process
      constraints hinder large-scale applications of this chemistry. These limitations
      are addressed by the development of a continuous-flow tube reactor, which has
      been demonstrated on several scales in the aerobic oxidation of alcohols. Use of
      a dilute oxygen gas source (8% O(2) in N(2)) ensures that the oxygen/organic
      mixture never enters the explosive regime, and efficient gas-liquid mixing in the
      reactor minimizes decomposition of the homogeneous catalyst into inactive Pd
      metal. These results provide the basis for large-scale implementation of
      palladium-catalyzed (and other) aerobic oxidation reactions for pharmaceutical
      synthesis.

PMID- 20694170
TI  - Properties of the Magnitude Terms of Orthogonal Scaling Functions.
AB  - The spectrum of the convolution of two continuous functions can be determined as
      the continuous Fourier transform of the cross-correlation function. The same can
      be said about the spectrum of the convolution of two infinite discrete sequences,
      which can be determined as the discrete time Fourier transform of the cross
      correlation function of the two sequences. In current digital signal processing,
      the spectrum of the contiuous Fourier transform and the discrete time Fourier
      transform are approximately determined by numerical integration or by densely
      taking the discrete Fourier transform. It has been shown that all three
      transforms share many analogous properties. In this paper we will show another
      useful property of determining the spectrum terms of the convolution of two
      finite length sequences by determining the discrete Fourier transform of the
      modified cross-correlation function. In addition, two properties of the magnitude
      terms of orthogonal wavelet scaling functions are developed. These properties are
      used as constraints for an exhaustive search to determine an robust lower bound
      on conjoint localization of orthogonal scaling functions.

PMID- 20694171
TI  - Independence Giving or Autonomy Taking? Childhood Predictors of Decision-Sharing
      Patterns Between Young Adolescents and Parents.
AB  - This article reports on a study of whether young adolescents make decisions
      autonomously, share decisions with their parents, or have decisions made for them
      by parents. Using a sample of 2,632 12-and 13-year-olds from the National
      Longitudinal Survey of Youth 1979 Child Survey we examine how childhood behavior
      and competence influence decision patterns in young adolescence. Individual
      models are used to test whether traits predict decision patterns, and sibling
      fixed-effects models allow us to estimate effects of child characteristics net of
      stable family contributions. In both individual and sibling fixed-effects models,
      children with higher verbal ability share more decision-making with parents.
      Children with greater mathematical aptitude and children who are impulsive are
      more likely to make decisions without consulting parents. The impulsivity effect
      is stronger in families with fewer resources. These results suggest that children
      directly and indirectly influence household decision-sharing patterns.

PMID- 20694172
TI  - A Non-Orthogonal Block-Localized Effective Hamiltonian Approach for Chemical and
      Enzymatic Reactions.
AB  - The effective Hamiltonian-molecular orbital and valence bond (EH-MOVB) method
      based on non-orthogonal block-localized fragment orbitals has been implemented
      into the program CHARMM for molecular dynamics simulations of chemical and
      enzymatic reactions, making use of semiempirical quantum mechanical models.
      Building upon ab initio MOVB theory, we make use of two parameters in the EH-MOVB
      method to fit the barrier height and the relative energy between the reactant and
      product state for a given chemical reaction to be in agreement with experiment or
      high-level ab initio or density functional results. Consequently, the EH-MOVB
      method provides a highly accurate and computationally efficient QM/MM model for
      dynamics simulation of chemical reactions in solution. The EH-MOVB method is
      illustrated by examination of the potential energy surface of the hydride
      transfer reaction from trimethylamine to a flavin cofactor model in the gas
      phase. In the present study, we employed the semiempirical AM1 model, which
      yields a reaction barrier that is more than 5 kcal/mol too high. We use a
      parameter calibration procedure for the EH-MOVB method similar to that employed
      to adjust the results of semiempirical and empirical models. Thus, the relative
      energy of these two diabatic states can be shifted to reproduce the experimental
      energy of reaction, and the barrier height is optimized to reproduce the desired
      (accurate) value by adding a constant to the off-diagonal matrix element. The
      present EH-MOVB method offers a viable approach to characterizing solvent and
      protein-reorganization effects in the realm of combined QM/MM simulations.

PMID- 20694173
TI  - Symbols Build Communication and Thought: The Role of Gestures and Words in the
      Development of Engagement Skills and Social-Emotional Concepts during
      Toddlerhood.
AB  - Social skills and symbol skills are positively associated in middle childhood,
      but the relation between these domains is less clear in newly verbal toddlers.
      Vygotsky (1934/1986) proposed that symbols are both tools for interaction and
      mental tools for thought. Do symbols help even very young children build skills
      for interacting with and conceptualizing the social world? Longitudinal data from
      108 children and mothers were collected when children were 14, 24, and 36 months.
      Children's gestures and words during mother-child interactions were used as
      symbol skill indicators to predict children's abilities to engage others and the
      number of social-emotional concepts children portray during play. In a series of
      growth models, words had a stronger effect on engagement skills while early
      gesture use predicted later development of social-emotional concepts. Therefore,
      even in early development, symbols serve as both communication tools and mental
      tools to construct understanding of the social-emotional world.

PMID- 20694174
TI  - Spirastrellolide Studies. Synthesis of the C(1)-C(25) Southern Hemispheres of
      Spirastrellolides A and B, Exploiting Anion Relay Chemistry.
AB  - Construction of the C(1)-C(25) southern fragments of both spirastrellolide A and
      B are described. Highlights of the syntheses include effective use of the three
      component anion relay chemistry (ARC) tactic recently introduced by our
      laboratory, a stereoselective spirocyclization via concomitant Ferrier reaction
      to elaborate the BC spiroketal and use of two dithiane unions to install the A
      ring as well as C(22)-C(25) fragment. The synthesis proceeded with longest linear
      sequences of 33 and 32 steps respectively for spirastrellolide A and
      spirastrellolide B.

PMID- 20694175
TI  - Molecular rotors: Synthesis and evaluation as viscosity sensors.
AB  - It has been shown that compounds containing the p-N,N,-dialkylaminobenzylidene
      cyanoacetate motif can serve as fluorescent non-mechanical viscosity sensors.
      These compounds, referred to as molecular rotors, belong to a class of
      fluorescent probes that are known to form twisted intramolecular charge-transfer
      complexes in the excited state. In this study we present the synthesis and
      spectroscopic characterization of these compounds as viscosity sensors. The
      effects of the molecular structure and electronic density of these rotors to the
      emission wavelength, fluorescence intensity and viscosity sensitivity are
      discussed.

PMID- 20694176
TI  - Tuning hydrogel properties and function using substituent effects.
AB  - The physical properties and function of hydrogels are shown to depend on the
      substituents present in three novel 1,3,5-tri-azaadamantane (TAA) cross-linkers.
      Gel stiffness and degradation rate at varied pHs could be predictably tuned with
      the cross-linker substituents used to form the gel. Subsequently, protein release
      from the hydrogel were controlled with chemical structure of the cross-linker.

PMID- 20694177
TI  - Partnership in the Treatment of Childhood Mental Health Problems: A Pediatric
      Perspective.
AB  - Pediatricians understand their role as promoting both the physical and mental
      health of children from birth until adulthood. Within the context of this long
      term relationship, parents approach clinicians to address a full range of
      behavioral concerns ranging from variations of normal development to major mental
      illness. In this commentary that builds upon the earlier manuscripts in this
      collection, we explore the pediatrician's role in mental health care through the
      example of attention-deficit hyperactivity disorder (ADHD). ADHD is an ideal
      prototype for the exploration of partnership in mental health care because ADHD
      is the most common neurobehavioral disorder in childhood, it is commonly treated
      in primary care settings, multiple evidence-based treatments exist, personal
      values strongly influence the acceptability of treatment, treatment adherence is
      often poor, and effective treatment relies on the collaboration of pediatricians
      with families, schools, and the mental health system. Through the use of the
      Chronic Care Model for Child Health that emphasizes the importance of optimizing
      and coordinating systems of care for effective partnership, the following
      manuscript reviews the challenges and opportunities for pediatricians partnering
      with families and schools to address mental health problems. Strategies
      highlighted in the preceding papers are discussed within the context of this
      model.

PMID- 20694178
TI  - Dealing with grief related to loss by death and chronic pain: suggestions for
      practice. Part 2.
AB  - OBJECTIVE: This paper, the second of two, represents a theoretical framework for
      interventions related to loss by death of someone close, or chronic pain. This
      work is based on our previous understanding where grief is considered an
      integrated experience which involves movements on several continua. METHODS: We
      have performed a comparison between two interventions dealing with grief and
      chronic pain using different designs. Interrelated experiences and processes were
      identified. RESULTS: Life phenomena like grief and loss caused by death and
      chronic pain, seem to have many qualities in common and may overlap each other. A
      common core containing emptiness, vulnerability and exhaustion is identified.
      DISCUSSION: Despite advances in research and thinking in recent years, several
      issues related to grief caused by death or chronic pain remain a challenge in
      clinical settings and research. When preparing interventions, we must pay
      attention to the relearning process, the common core and the interplay between
      these bodily expressions. CONCLUSION: We believe there is a value in future
      research and practice to consider losses caused by death and chronic pain,
      together as well as separately. Our comprehensive approach indicates that
      understanding the processes involved in one sort of grief may help understand the
      processes involved in the other.

PMID- 20694179
TI  - Exploring patients' perceptions for insulin therapy in type 2 diabetes: a
      Brazilian and Canadian qualitative study.
AB  - OBJECTIVE: To explore which attributes of insulin therapy drive patients'
      preferences for management in Canada and Brazil. METHODS: A qualitative design
      was implemented in which a total of 32 patients with type 2 diabetes from Canada
      and Brazil, were interviewed in one of the 4 focus groups, or 16 individual
      interviews. Eighteen participants (56%) were women and fourteen participants
      (44%) were men (15 insulin nonusers and 17 insulin users). Two focus groups of 4
      participants each and 9 individual interviews were conducted in Brazil. In
      Canada, 2 focus groups of 4 participants each and 7 individual interviews were
      conducted. A framework analysis was used to analyse all data. RESULTS: Brazilian
      participants, when considering two insulin treatments, would prefer the one that
      had fewer side-effects (specially hypoglycemia events), was noninjectable, had
      the lowest cost and was most effective. Meanwhile, Canadian participants would
      prefer a treatment that had fewer side-effects (specially weight gain), was less
      invasive, was more convenient and was most effective. CONCLUSIONS: Finding the
      insulin-delivery system and the attributes of insulin therapy that best meet
      patients' preferences may lead to improved control, through improved compliance,
      which may ultimately reduce the financial burden of the disease and improve
      quality of life.

PMID- 20694180
TI  - Individual patients hold different beliefs to prescription medications to which
      they persist vs nonpersist and persist vs nonfulfill.
AB  - OBJECTIVE: Our objective was to explore whether adults hold different beliefs
      about medications to which they persist vs nonpersist and persist vs nonfulfull.
      METHODS: We conducted a cross-sectional survey of adults with asthma,
      hypertension, diabetes, hyperlipidemia, osteoporosis, or other cardiovascular
      disease from the Harris Interactive Chronic Illness Panel. A quota was set to
      obtain a sample of respondents who were persistent to a medication for one
      disease and nonpersistent or nonfulfilling to a medication for a second,
      different disease. Respondents completed 32 items yielding five multi-item
      scales: perceived need for medication (k = 12), side-effect concerns (k = 5),
      medication-safety concerns (k = 5), perceived disease severity (k = 3), and
      knowledge about the prescribed medication (k = 7). Respondents completed the 32
      items twice - once for their persistent medication and a second time for their
      nonpersistent or nonfulfilling medication. Paired sample t-tests (bivariate) and
      generalized estimating equations (GEE) models (multivariate) were used to test
      the study hypotheses. RESULTS: Overall, 178 respondents were sampled for being
      persistent to one medication and nonpersistent to another, while 48 respondents
      were persistent to one medication and nonfulfilling to a second. For the
      medication to which an individual patient was persistent vs nonpersistent, there
      was significantly higher perceived need, fewer side-effect concerns, higher
      perceived disease severity, and better knowledge about the medication. For the
      medication to which an individual patient was persistent vs nonfulfilling, there
      was significantly higher perceived need, fewer side-effect concerns, and better
      knowledge about the medication. CONCLUSION: Individual patients hold different
      beliefs about medications to which they persist vs nonpersist or nonfulfill.
      Patients exhibit different medication-taking behaviors for different medications
      because they weigh the perceived risks and benefits for each medication
      separately. These results suggest that adherence interventions should be tailored
      to patients' beliefs about specific medications.

PMID- 20694181
TI  - Maternal and neonatal complications in mothers aged under 18 years.
AB  - OBJECTIVE: The aim of this study was to evaluate maternal and neonatal
      complications in mothers delivering babies when aged younger than 18 years.
      METHODS: In this retrospective study, all labors attended during a one-year
      period at Alzahra Referral Hospital were evaluated for level of risk. We recorded
      maternal risk factors, including age, type of delivery, health status, and other
      factors including marital status and familial marriage. Neonates were evaluated
      according to prematurity, birth weight, and general health status. RESULTS: There
      were 186 mothers under the age of 18 years, comprising 2.6% of all deliveries at
      our institution. We divided them in two groups according to age, ie, Group 1
      (under 15 years) and Group 2 (15-18 years). Rates of normal vaginal delivery and
      cesarean section were 83% and 17%, respectively. The prevalence of eclampsia and
      pre-eclampsia in Group 1 was twice that in Group 2. Rates of still birth,
      prematurity, low birth weight and very low birth weight were higher in Group 1
      than in Group 2 (9.09%, 18.1%, 16.7%, and 4.5% versus 4.6%, 13.9%, 13.6%, and
      1.9%, respectively). The rate of familial marriage was 18%, and 16% of the
      offspring of these marriages were complicated by congenital malformations and
      still birth. These complications were twice as common in Group 1 compared with
      Group 2 (11% versus 5%, respectively). CONCLUSION: Maternal age under 18 years is
      a risk factor for complications in both mothers and neonates, and even more so in
      mothers aged younger than 15 years.

PMID- 20694182
TI  - The efficacy of herbal therapy on quality of life in patients with breast cancer:
      self-control clinical trial.
AB  - BACKGROUND: Mounting evidence indicates that herbal therapy is effective in
      alleviating anxiety, lessening cancer treatment-related side-effects, and
      facilitating rehabilitation. This is the first trial to examine the herbal
      therapy of combined yunzhi and danshen on quality of life among breast cancer
      patients. METHODS: A multicenter, longitudinal, and self-control study was used.
      Eighty-two breast cancer patients were given combined yunzhi and danshen capsules
      for six months on a daily basis. Data collection including quality of life,
      vitality status and adverse effects were taken. RESULTS: Results showed a
      significant improvement in physical function, role-physical, role-emotion and
      health transition (P < 0.05). Patients also reported less fatigue, better quality
      of sleep, better appetite, more regular bowel movements and more stable emotions
      (P < 0.05). As far as side-effects were concerned, only mild discomforts
      including sore throat (13.4%) and dry mouth (9.8%) were recorded. CONCLUSION: The
      findings add clinical evidence to support the beneficial effects of herbal
      therapy on quality of life and vitality status in breast cancer patients.
      Therefore, herbal therapy has a potentially important role to play in managing
      psychological distress in cancer patients. This study also suggests that herbal
      therapy is clinically acceptable and can be used safely with breast cancer
      patients.

PMID- 20694183
TI  - Development of clinical utility of zoledronic acid and patient considerations in
      the treatment of osteoporosis.
AB  - Osteoporosis is a major health concern, which results in the increased risk of
      fractures. There is a high risk for the first or consecutive fractures leading to
      considerable morbidity and debilitating consequences if osteoporosis is
      untreated. Currently, bisphosphonates are the mainstay of treatment for
      osteoporosis though long-term persistence and adherence to bisphosphonates,
      especially those taken orally, remain low. This medication noncompliance has
      serious consequences on osteoporotic patients as it is associated with a
      significantly higher fracture risk. Intravenous (IV) zoledronic acid (ZOL),
      developed to increase compliance by overcoming the frequent and burdensome dosing
      requirements of oral bisphosphonates, is the first and the only once-yearly
      bisphosphonate globally approved for use in the treatment of up to 6 indications
      of osteoporosis. Several clinical studies have documented that a single infusion
      of IV ZOL resulted in decreased bone turnover and improved bone density for at
      least 12 months post infusion. This article traces the development of ZOL's
      clinical utility and evaluates its patient preference by collating data from all
      major clinical trials, studying the efficacy and safety of ZOL in the treatment
      of osteoporosis and other benign bone disorders.

PMID- 20694184
TI  - The utility of an electronic adherence assessment device in type 2 diabetes
      mellitus: a pilot study of single medication.
AB  - OBJECTIVES: The primary objective of this pilot study was to determine if the
      Medication Event Monitoring System (MEMS) is capable of providing meaningful
      estimates of compliance within the indigenous Qatari population. The secondary
      objective was to highlight any specific problems which might be associated with
      the use of MEMS within this population. METHOD: A sample of adult diabetic Qatari
      patients attending an outpatient diabetic clinic were administered a Knowledge,
      Attitude, and Practices (KAP) questionnaire and then dispensed one of their
      regular medications in a MEMS((R))-fitted bottle. Data contained in the MEMS((R))
      were downloaded after the patients returned for a refill and adherence was
      estimated using 2 methods: pill count and MEMS((R)) data. RESULTS: A total of 54
      patients agreed to participate in this pilot study. Adherence to daily doses was
      67.7% and with regimen 13.7%. No correlation was found between adherence assessed
      by pill count and MEMS((R)). The association between KAP and adherence was
      generally poor. A number of other issues and challenges in the use of MEMS((R))
      that could affect its utility were noted and will be discussed. CONCLUSIONS: Our
      results revealed problems associated with the use of MEMS((R)) that could affect
      its usefulness in assessing adherence in this part of the world. Some issues
      identified in this pilot study included retrieving the MEMS((R)), registering
      extra opening of MEMS((R)), desire to hoard medicine by taking doses at different
      frequency than recorded in MEMS((R)). All these issues could be closely
      associated with the attitudes and practices of the patients, as demonstrated by
      our KAP analysis and correlations.

PMID- 20694185
TI  - Is there a nonadherent subtype of hypertensive patient? A latent class analysis
      approach.
AB  - To determine subtypes of adherence, 636 hypertensive patients (48% White, 34%
      male) reported adherence to medications, diet, exercise, smoking, and home blood
      pressure monitoring. A latent class analysis approach was used to identify
      subgroups that adhere to these five self-management behaviors. Fit statistics
      suggested two latent classes. The first class (labeled "more adherent") included
      patients with greater probability of adhering to recommendations compared with
      the second class (labeled "less adherent") with regard to nonsmoking (97.7%
      versus 76.3%), medications (75.5% versus 49.5%), diet (70.7% versus 46.9%),
      exercise (63.4% versus 27.2%), and blood pressure monitoring (32% versus 3.4%).
      Logistic regression analyses used to characterize the two classes showed that
      "more adherent" participants were more likely to report full-time employment,
      adequate income, and better emotional and physical well-being. Results suggest
      the presence of a less adherent subtype of hypertensive patients. Behavioral
      interventions designed to improve adherence might best target these at-risk
      patients for greater treatment efficiency.

PMID- 20694186
TI  - Antipsychotic adherence, switching, and health care service utilization among
      Medicaid recipients with schizophrenia.
AB  - OBJECTIVE: To evaluate health care resource utilization in patients with
      schizophrenia who continued newly prescribed antipsychotic medications, compared
      with those switching to different treatments. METHODS: Adults with schizophrenia
      in the California Medicaid (MediCal) database who initiated treatment with index
      medications in 1998-2001, were classified as having: 1) abandoned antipsychotic
      medications; 2) switched to another medication; or 3) continued with the index
      antipsychotic, for up to 6 months after the index date. RESULTS: Of 2300 patients
      meeting eligibility criteria, 1382 (60.1%) continued index medications, 480
      (20.9%) switched, and 438 (19.0%) abandoned antipsychotic treatment. Utilization
      in several resource categories occurred significantly more frequently among
      patients whose regimens were switched (vs those continuing index medications).
      These included using psychiatric (24.2% vs 14.5%; P < 0.001) or nonpsychiatric
      (31.5% vs 24.3%; P < 0.05) emergency services; being admitted to a hospital
      (10.6% vs 7.4%; P < 0.05); making nonpsychiatric outpatient hospital visits
      (43.3% vs 36.4%; P < 0.05) or nonpsychiatric physician visits (62.7% vs 56.4%; P
      < 0.05); and using other outpatient psychiatric (53.3% vs 40.7%; P < 0.001) or
      nonpsychiatric (82.7% vs 74.6%; P < 0.001) services. CONCLUSIONS: Switching
      antipsychotic medications is associated with significantly increased health care
      resource utilization (vs continuing treatment).

PMID- 20694187
TI  - AUTOMATIC IDENTIFICATION AND DELINEATION OF GERM LAYER COMPONENTS IN H&E STAINED
      IMAGES OF TERATOMAS DERIVED FROM HUMAN AND NONHUMAN PRIMATE EMBRYONIC STEM CELLS.
AB  - We present a methodology for the automatic identification and delineation of germ
      layer components in H&E stained images of teratomas derived from human and
      nonhuman primate embryonic stem cells. A knowledge and understanding of the
      biology of these cells may lead to advances in tissue regeneration and repair,
      the treatment of genetic and developmental syndromes, and drug testing and
      discovery. As a teratoma is a chaotic organization of tissues derived from the
      three primary embryonic germ layers, H&E teratoma images often present multiple
      tissues, each of having complex and unpredictable positions, shapes, and
      appearance with respect to each individual tissue as well as with respect to
      other tissues. While visual identification of these tissues is time-consuming, it
      is surprisingly accurate, indicating that there exist enough visual cues to
      accomplish the task. We propose automatic identification and delineation of these
      tissues by mimicking these visual cues. We use pixel-based classification,
      resulting in an encouraging range of classification accuracies from 74.9% to
      93.2% for 2- to 5-tissue classification experiments at different scales.

PMID- 20694188
TI  - Chain- and Regioselective Ethylene and Styrene Dimerization Reactions Catalyzed
      by a Well-Defined Cationic Ruthenium-Hydride Complex: New Insights on the Styrene
      Dimerization Mechanism.
AB  - The cationic ruthenium-hydride complex [(eta(6)-C(6)H(6))(PCy(3))(CO)RuH](+)BF(4)
      (-) was found to be a highly regioselective catalyst for the ethylene
      dimerization reaction to give 2-butene products (TOF = 1910 h(-1), >95%
      selectivity for 2-butenes). The dimerization of styrene exclusively produced the
      head-to-tail dimer (E)-PhCH(CH(3))CH=CHPh at an initial turnover rate of 2300 h(
      1). A rapid and extensive H/D exchange between the vinyl hydrogens of styrene
      d(8) and 4-methoxystyrene was observed within 10 min without forming the dimer
      products at room temperature. The inverse deuterium isotope effect of k(H)/k(D) =
      0.77+/-0.10 was measured from the first order plots on the dimerization reaction
      of styrene and styrene-d(8) in chlorobenzene at 70 degrees C. The pronounced
      carbon isotope effect on both vinyl carbons of styrene as measured by using
      Singleton's method ((13)C(recovered)/(13)C(virgin) at C(1) = 1.096 and C(2) =
      1.042) indicates that the C-C bond formation is the rate-limiting step for the
      dimerization reaction. The Eyring plot of the dimerization of styrene in the
      temperature range of 50-90 degrees C led to DeltaH(double dagger) = 3.3(6)
      kcal/mol and DeltaS(double dagger) = -35.5(7) e.u. An electrophilic addition
      mechanism has been proposed for the dimerization of styrene.

PMID- 20694189
TI  - Preparation and Characterization of Tetrabenazine Enantiomers against Vesicular
      Monoamine Transporter 2.
AB  - As a clinical medication for the treatment of hyperkinetic movement disorders, in
      conditions such as Huntington's disease, tetrabenazine (TBZ) has been always used
      in its racemic form. To establish whether or not its beneficial therapeutic
      actions are enantiospecific, a practical total synthetic route was developed to
      yield each enantiomeric form to allow their chemical and pharmacological
      characterization. We briefly summarize the total synthesis of TBZ and report a
      detailed procedure for resolution of TBZ into its enantiomers, (+)-TBZ and (-)
      TBZ. This allowed determination of the optical rotation and absolute
      configurations of each TBZ enantiomer, based on X-ray crystallographic analysis,
      together with characterization of their inhibitory action at the vesicular
      monoamine transporter 2, where (+)-TBZ proved three-fold more active than (-)
      TBZ.

PMID- 20694190
TI  - Comparing the Ethnic Identity and Well-Being of Adopted Korean Americans with
      Immigrant/U.S.-Born Korean Americans and Korean International Students.
AB  - This study compared the ethnic identity and well-being of Korean Americans who
      were adopted internationally with immigrant/U.S.-born Korean Americans and Korean
      international students, as well as the relationship between ethnic identity and
      well-being for each group. One-hundred and seven college students completed
      measures of ethnic identity and subjective well-being. Immigrant/U.S.-born Korean
      Americans had higher ethnic identity scores than the other two groups.
      Immigrant/U.S.-born Korean Americans also had higher positive affect scores than
      international students. Ethnic identity was positively correlated with positive
      affect for all three groups (r's = .27 - .34), but was negatively correlated with
      negative affect for international students (r = -.44). Overall, the results
      suggest that ethnic identity, although slightly lower than non-adopted peers, is
      relevant to the well-being of adopted Korean American college students.

PMID- 20694191
TI  - SYNTHESIS OF SPIROBORATE ESTERS FROM 1,2-AMINOALCOHOLS, ETHYLENE GLYCOL AND
      TRIISOPROPYL BORATE: PREPARATION OF (S)-1-(1,3,2-DIOXABOROLAN-2-YLOXY)-3-METHYL
      1,1-DIPHENYLBUTAN-2-AMINE.

PMID- 20694193
TI  - Detection of cervical intraepithelial neoplasias and cancers in cervical tissue
      by in vivo light scattering.
AB  - OBJECTIVE: To examine the utility of in vivo elastic light scattering
      measurements to identify cervical intraepithelial neoplasias (CIN) 2/3 and
      cancers in women undergoing colposcopy and to determine the effects of patient
      characteristics such as menstrual status on the elastic light scattering
      spectroscopic measurements. MATERIALS AND METHODS: A fiber optic probe was used
      to measure light transport in the cervical epithelium of patients undergoing
      colposcopy. Spectroscopic results from 151 patients were compared with
      histopathology of the measured and biopsied sites. A method of classifying the
      measured sites into two clinically relevant categories was developed and tested
      using five-fold cross-validation. RESULTS: Statistically significant effects by
      age at diagnosis, menopausal status, timing of the menstrual cycle, and oral
      contraceptive use were identified, and adjustments based upon these measurements
      were incorporated in the classification algorithm. A sensitivity of 77+/-5% and a
      specificity of 62+/-2% were obtained for separating CIN 2/3 and cancer from other
      pathologies and normal tissue. CONCLUSIONS: The effects of both menstrual status
      and age should be taken into account in the algorithm for classifying tissue
      sites based on elastic light scattering spectroscopy. When this is done, elastic
      light scattering spectroscopy shows good potential for real-time diagnosis of
      cervical tissue at colposcopy. Guiding biopsy location is one potential near-term
      clinical application area, while facilitating "see and treat" protocols is a
      longer term goal. Improvements in accuracy are essential.

PMID- 20694194
TI  - Portable, battery-operated, low-cost, bright field and fluorescence microscope.
AB  - This study describes the design and evaluation of a portable bright-field and
      fluorescence microscope that can be manufactured for $240 USD. The microscope
      uses a battery-operated LED-based flashlight as the light source and achieves a
      resolution of 0.8 microm at 1000x magnification in fluorescence mode. We tested
      the diagnostic capability of this new instrument to identify infections caused by
      the human pathogen, Mycobacterium tuberculosis. Sixty-four direct,
      decontaminated, and serially diluted smears were prepared from sputa obtained
      from 19 patients suspected to have M. tuberculosis infection. Slides were stained
      with auramine orange and evaluated as being positive or negative for M.
      tuberculosis with both the new portable fluorescence microscope and a laboratory
      grade fluorescence microscope. Concordant results were obtained in 98.4% of
      cases. This highly portable, low cost, fluorescence microscope may be a useful
      diagnostic tool to expand the availability of M. tuberculosis testing at the
      point-of-care in low resource settings.

PMID- 20694195
TI  - Recruitment strategies and colony size in ants.
AB  - Ants use a great variety of recruitment methods to forage for food or find new
      nests, including tandem running, group recruitment and scent trails. It has been
      known for some time that there is a loose correlation across many taxa between
      species-specific mature colony size and recruitment method. Very small colonies
      tend to use solitary foraging; small to medium sized colonies use tandem running
      or group recruitment whereas larger colonies use pheromone recruitment trails.
      Until now, explanations for this correlation have focused on the ants' ecology,
      such as food resource distribution. However, many species have colonies with a
      single queen and workforces that grow over several orders of magnitude, and
      little is known about how a colony's organization, including recruitment methods,
      may change during its growth. After all, recruitment involves interactions
      between ants, and hence the size of the colony itself may influence which
      recruitment method is used--even if the ants' behavioural repertoire remains
      unchanged. Here we show using mathematical models that the observed correlation
      can also be explained by recognizing that failure rates in recruitment depend
      differently on colony size in various recruitment strategies. Our models focus on
      the build up of recruiter numbers inside colonies and are not based on optimality
      arguments, such as maximizing food yield. We predict that ant colonies of a
      certain size should use only one recruitment method (and always the same one)
      rather than a mix of two or more. These results highlight the importance of the
      organization of recruitment and how it is affected by colony size. Hence these
      results should also expand our understanding of ant ecology.

PMID- 20694192
TI  - Research into Specific Modulators of Vascular Sex Hormone Receptors in the
      Management of Postmenopausal Cardiovascular Disease.
AB  - Cardiovascular disease (CVD) is more common in men and postmenopausal women than
      premenopausal women, suggesting vascular benefits of female sex hormones. Studies
      on the vasculature have identified estrogen receptors ERalpha, ERbeta and a novel
      estrogen binding membrane protein GPR30, that mediate genomic and/or non-genomic
      effects. Estrogen promotes endothelium-dependent relaxation by inducing the
      production/activity of nitric oxide, prostacyclin, and hyperpolarizing factor,
      and inhibits the mechanisms of vascular smooth muscle contraction including
      [Ca(2+)](i), protein kinase C, Rho kinase and mitogen-activated protein kinase.
      Additional effects of estrogen on the cytoskeleton, matrix metalloproteinases and
      inflammatory factors contribute to vascular remodeling. However, the experimental
      evidence did not translate into vascular benefits of menopausal hormone therapy
      (MHT), and the HERS, HERS-II and WHI clinical trials demonstrated adverse
      cardiovascular events. The discrepancy has been partly related to delayed MHT and
      potential changes in the vascular ER amount, integrity, affinity, and downstream
      signaling pathways due to the subjects' age and preexisting CVD. The adverse
      vascular effects of MHT also highlighted the need of specific modulators of
      vascular sex hormone receptors. The effectiveness of MHT can be improved by
      delineating the differences in phramcokinetics and pharmacodynamics of natural,
      synthetic, and conjugated equine estrogens. Estriol, "hormone bioidenticals" and
      phytoestrogens are potential estradiol substitutes. The benefits of low dose MHT,
      and transdermal or vaginal estrogens over oral preparations are being evaluated.
      Specific ER modulators (SERMs) and ER agonists are being developed to maximize
      the effects on vascular ERs. Also, the effects of estrogen are being examined in
      the context of the whole body hormonal environment and the levels of progesterone
      and androgens. Thus, the experimental vascular benefits of estrogen can be
      translated to the outcome of MHT in postmenopausal CVD, as more specific
      modulators of sex hormone receptors become available and are used at the right
      dose, route of administration and timing, depending on the subject's age and
      preexisting cardiovascular condition.

PMID- 20694196
TI  - Methyl sulfone induces loss of metastatic properties and reemergence of normal
      phenotypes in a metastatic cloudman S-91 (M3) murine melanoma cell line.
AB  - BACKGROUND: The most deadly form of cancer is not lung or colon, breast or
      prostate; it is any cancer that has become metastatic. Mortality due to
      metastatic melanoma, one of the most aggressive and deadly cancers, has increased
      steadily over the last several decades. Unfortunately, the arsenal of
      chemotherapeutic agents available today is most often unsuccessful at extending
      and improving the life expectancy of afflicted individuals. We sought to identify
      an effective and nontoxic agent against metastatic melanoma.
      METHODOLOGY/PRINCIPAL FINDINGS: We chose to study Cloudman S-91 mouse melanoma
      cells (sub-clone M3, CCL53.1) because these cells are highly aggressive and
      metastatic, representing one of the deadliest types of cancer. Melanoma cells
      also had an experimental advantage because their morphology, which is easily
      monitored, relates to the physiology of metastatic cells and normal melanocytes.
      We chose to test methyl sulfone as a chemotherapeutic agent for two reasons.
      Because of its chemical structure, we speculated a potential anti-cancer activity
      by targeting microtubules. Equally important, methyl sulfone has a well
      established safety profile in humans. Surprisingly, we found that malignant
      melanoma cells exposed to methyl sulfone demonstrated the loss of phenotypes
      characteristic of malignant cells, and the reemergence of phenotypes
      characteristic of healthy melanocytes. Briefly, over time methyl sulfone induced
      contact inhibition, loss of ability to migrate through an extracellular matrix,
      loss of anchorage-independent growth, proper wound healing followed by contact
      inhibition, irreversible senescence followed by arborization with melanosomes in
      arbors as seen in normal melanocytes. CONCLUSIONS/SIGNIFICANCE: Methyl sulfone
      may have clinical potential as a non-toxic agent effective against metastatic
      melanoma. Additionally, methyl sulfone has promise as a tool to explore molecular
      mechanisms of metastatic transformation as well as fundamental processes such as
      cell migration, contact inhibition, wound healing and cellular senescence.

PMID- 20694202
TI  - Tripodal transmembrane transporters for bicarbonate.
AB  - Easy-to-make tripodal tris-thiourea receptors based upon tris(2-aminoethyl)amine
      are capable of chloride/bicarbonate transport and as such represent a new class
      of bicarbonate transport agent.

PMID- 20694203
TI  - Pyrrolizine-1,3-dione.
AB  - Pyrrolizine-1,3-dione 4 was made by oxidation of the alcohol 2 using pyridinium
      chlorochromate. The dione 4 shows ketone properties (e.g. formation of DNP
      derivative 11) and, in common with other pyrrolizinones, the lactam unit is
      readily ring-opened by methanol under basic conditions. The active methylene unit
      of 4 couples readily with diazonium salts to provide the hydrazone 15 whose
      structure was confirmed by X-ray crystallography. The 'Meldrumsated' derivative
      18 exists exclusively as the tautomer 18F; flash vacuum pyrolysis (FVP) of 18 at
      700 degrees C gives the pyronopyrrolizine 20 exclusively. Reaction of 4 with DMF
      acetal gives the dimethylaminomethylene derivative 22 which exists as a mixture
      of rotamers at room temperature.

PMID- 20694204
TI  - Systematic microcanonical analyses of polymer adsorption transitions.
AB  - In detailed microcanonical analyses of densities of states obtained by extensive
      multicanonical Monte Carlo computer simulations, we investigate the caloric
      properties of conformational transitions that adsorbing polymers experience near
      attractive substrates. For short chains and strong surface attraction, the
      microcanonical entropy turns out to be a convex function of energy in the
      transition regime, indicating that surface-entropic effects are relevant. Albeit
      known to be a continuous transition in the thermodynamic limit of infinitely long
      chains, the adsorption transition of nongrafted finite-length polymers thus
      exhibits a clear signature of a first-order-like transition, with coexisting
      phases of adsorbed and desorbed conformations. Another remarkable consequence of
      the convexity of the microcanonical entropy is that the transition is accompanied
      by a decrease of the microcanonical temperature with increasing energy. Since
      this is a characteristic physical effect it might not be ignored in analyses of
      cooperative macrostate transitions in finite systems.

PMID- 20694205
TI  - Room-temperature ionic liquid assisted fabrication of sensitive electrochemical
      immunosensor based on ordered macroporous gold film.
AB  - A novel label-free highly sensitive electrochemical impedance spectroscopy (EIS)
      immunosensor was fabricated based on the highly ordered macroporous gold film
      (HOMGF) in the presence of room-temperature ionic liquid (IL) for the detection
      of human Apolipoprotein B-100 (ApoB-100). The antibody of ApoB-100 (Ab) was
      adsorbed directly onto the HOMGF electrode surface and maintained its
      bioactivity. After the residual active sites at the electrode were passivated by
      BSA, the mixture of BMIm(+)BF(4)(-) and silica sol was dropped onto the electrode
      to entrap the adsorbed Ab and BSA molecules firmly. The addition of IL could
      prevent the inactivation of Ab by releasing alcohol during the sol-gel process,
      and the conductivity of the IL-gel membrane was increased. Of particular interest
      is the fact that the fabricated immunosensor could be used at 60  degrees C. This
      could be attributed to the interconnected porosity of the IL-gel membrane, which
      can prevent Ab from unfolding and losing its bioactivities. The immunosensor also
      exhibited a highly sensitive response to ApoB-100 with the lowest concentration
      of 5 fg mL(-1). The detection of ApoB-100 levels in five sera samples obtained
      from hospital showed acceptable accuracy with that using commercial
      immunonephelometry method.

PMID- 20694206
TI  - Molecular characterisation of post-bio-electrosprayed human brain astrocytoma
      cells.
AB  - Bio-electrospraying (BES) is a method for directly jetting living cells under
      conditions that allow their distribution in the x, y, and z axes. Previous work
      has been focused on achieving jetting in stable cone-jet mode, which is required
      for precision placement, and these studies have demonstrated that there are no
      significant effects of bio-electrospraying on cell morphology or viability. In
      this work, we examine the biological properties of bio-electrosprayed cells using
      assays of cellular function that range from the molecular level through to
      integrated cellular systems, and include proteomics, signal transduction, cell
      growth and proliferation, and the characterisation of apoptotic blebs. From these
      molecular methods, we have determined that bio-electrospraying, under the
      electric field conditions used to achieve stable cone-jet mode, causes no
      alterations to the biological properties and function of the cells being jetted.
      Bio-electrosprayed and control cells had similar viability, proliferation
      properties and virtually indistinguishable cell cycle profiles. The biophysical
      properties of large conducting (BK) potassium channels were unchanged, as were
      the pharmacological responses of the endogenous muscarinic and exogenous P2Y(11)
      receptors, both of which are cell surface receptors of the 7TM superfamily.
      Proteomic analyses revealed that although three proteins had subtle differences
      in expression level between bio-electrosprayed and control cells, none of these
      fold differences was above the 1.5-fold cut-off threshold required for further
      analyses. These findings support the further development of bio-electrosprays as
      a viable technology for a wide diversity of tissue engineering, regenerative
      biology, advanced cellular therapeutics and medicinal applications, having
      significance in the clinic.

PMID- 20694207
TI  - Single-walled carbon nanotube chemoresistive label-free immunosensor for salivary
      stress biomarkers.
AB  - The present work is focused on the development, analytical characterization and
      evaluation of selective and sensitive SWNT-chemiresistor immunosensor for the
      label-free detection of salivary alpha-amylase (SAA). SWNTs were aligned to
      bridge lithographically patterned gold microelectrodes using AC dielectrophoresis
      followed by functionalization with anti-SAA antibodies. The nano-immunosensors
      exhibited excellent sensitivity over the clinically relevant range (19 to 308 U
      ml(-1)) with a limit of detection (LOD) of 6 ug ml(-1) (0.6 U ml(-1)) and 7.8 ug
      ml(-1) (0.78 U ml(-1)) in phosphate buffer and artificial saliva, respectively,
      and no interference from other components of saliva. This label-free nano
      immunosensor technology has potential application in clinical diagnosis for
      stress biomarkers expressed in human saliva at the point-of-care.

PMID- 20694209
TI  - Shape control of platinum and palladium nanoparticles for catalysis.
AB  - Platinum and palladium are important catalysts for a wide variety of industrial
      processes. With the increasing demands of these materials, the development of
      high-performance catalysts is an important area of research, and as a result,
      shape control synthesis has become one of the leading research focuses. This
      minireview surveys the different approaches in solution-phase synthesis that have
      been successfully adopted for achieving shaped platinum and palladium
      nanoparticles that are enclosed with specific crystallographic facets. In
      addition, catalytic studies of the shaped nanoparticles are highlighted, in which
      promising results have been reported in terms of enhanced activity and
      selectivity. The future outlook discusses the aspects in synthesis and catalysis
      to be considered for the development of highly efficient and effective catalysts.

PMID- 20694208
TI  - High-performance nanostructured MR contrast probes.
AB  - Magnetic resonance imaging (MRI) has become a powerful technique in biological
      molecular imaging and clinical diagnosis. With the rapid progress in nanoscale
      science and technology, nanostructure-based MR contrast agents are undergoing
      rapid development. This is in part due to the tuneable magnetic and cellular
      uptake properties, large surface area for conjugation and favourable
      biodistribution. In this review, we describe our recent progress in the
      development of high-performance nanostructured MR contrast agents. Specifically,
      we report on Gd-enriched nanostructured probes that exhibit T(1) MR contrast and
      superparamagnetic Fe(3)O(4) and CoFe(2)O(4) nanostructures that display T(2) MR
      contrast enhancement. The effects of nanostructure size, shape, assembly and
      surface modification on relaxivity are described. The potential of these contrast
      agents for in vitro and in vivo MR imaging with respect to colloidal stability
      under physiological conditions, biocompatibility, and surface functionality are
      also evaluated.

PMID- 20694210
TI  - Microemulsion-based synthesis of nanoscaled silver hollow spheres and direct
      comparison with massive particles of similar size.
AB  - Nanoscale silver hollow spheres are first prepared via a microemulsion approach
      with 15-20 nm as the outer diameter, 3-5 nm as the wall thickness, and 10-15 nm
      as the diameter of the inner cavity. The presence of hollow spheres is confirmed
      by electron microscopy (SEM, BF-/HAADF-STEM, HRTEM) as well as by X-ray
      diffraction with a line-shape analysis to characterize the microcrystalline
      properties. In addition to the hollow spheres, massive silver nanoparticles of
      similar size (outer diameter of 15-20 nm) are gained via microemulsions. Based on
      the similarity of experimental conditions and the resulting particle size, as
      prepared silver hollow spheres and massive nanoparticles are used to compare
      their optical properties and surface-plasmon resonance. In contrast to reducing
      the diameter of massive particles, "hollowing" of silver nanoparticles leads to a
      red-shift of the plasmon resonance. With a red shift of about 33 nm in the case
      of the hollow spheres, a quantum-size effect is indeed observed and in accordance
      with the thin sphere wall.

PMID- 20694211
TI  - A universal and ready-to-use heterotrifunctional cross-linking reagent for facile
      synthetic access to sophisticated bioconjugates.
AB  - We describe for the first time, the synthesis and some bioconjugation
      applications of an original heterotrifunctional cross-linking reagent (also named
      tripod) bearing three different bioorthogonal functional groups which are fully
      compatible amongst themselves. Contrary to the first generation tripod recently
      reported by us (Org. Biomol. Chem., 2008, 6, 3065), the use of an azido group
      instead of the nucleophile-sensitive active carbamate moiety enables us to reach
      the targeted chemical orthogonality without the use of temporary aminooxy- and
      thiol protecting groups. Thus, the preparation of sophisticated bioconjugates
      through the sequential derivatisation of the tripod by means of copper-mediated
      1,3-dipolar cycloaddition, oxime ligation and aqueous compatible mild thiol
      alkylation reactions, is significantly simpler and more convenient. The
      chemoselective bioconjugation protocols were optimised through the preparation of
      FRET cassettes based on cyanine and/or xanthene fluorescent dye pairs and
      subsequent anchoring to fragile biomolecules. The applicability of this universal
      cross-linking reagent was also illustrated by the preparation of biochips
      suitable for aflatoxin B1 detection through the SPIT-FRI method.

PMID- 20694216
TI  - Droplet-based microfluidic system for multicellular tumor spheroid formation and
      anticancer drug testing.
AB  - Creating multicellular tumor spheroids is critical for characterizing anticancer
      treatments since it may provide a better model than monolayer culture of tumor
      cells. Moreover, continuous dynamic perfusion allows the establishment of long
      term cell culture and subsequent multicellular spheroid formation. A droplet
      based microfluidic system was used to form alginate beads with entrapped breast
      tumor cells. After gelation, the alginate beads were trapped in microsieve
      structures for cell culture in a continuous perfusion system. The alginate
      environment permitted cell proliferation and the formation of multicellular
      spheroids was observed. The dose-dependent response of the tumor spheroids to
      doxorubicin, and anticancer drug, showed multicellular resistance compared to
      conventional monolayer culture. The microsieve structures maintain constant
      location of each bead in the same position throughout the device seeding process,
      cell proliferation and spheroid formation, treatment with drug, and imaging,
      permitting temporal and spatial tracking.

PMID- 20694217
TI  - Characterizing the connectivity of poly-ubiquitin chains by selected reaction
      monitoring mass spectrometry.
AB  - Protein ubiquitination is an essential post-translational modification (PTM)
      involved in the regulation of a variety of cellular functions, including
      transcription and protein degradation. Proteins can be both mono- or poly
      ubiquitinated. Poly-ubiquitin chains vary in the manner by which the ubiquitin
      proteins are linked and their total length. Different poly-ubiquitin structures
      are thought to specify different fates for the target protein but the correlation
      between poly-ubiquitin structures and their specific cellular function(s) is not
      well understood. We have developed a set of specific and quantitative targeted
      mass spectrometry assays to determine the frequency of different types of inter
      ubiquitin linkages in poly-ubiquitin chains relative to the total ubiquitin
      concentration. We chemically synthesized heavy isotope labeled reference peptides
      that represent the products generated by tryptic digestion of the known forms of
      inter-ubiquitin links for the yeast Saccharomyces cerevisiae and human, in
      addition to all peptides from tryptic digestion of a single ubiquitin molecule
      for these two species. We used these peptides to develop optimized Selected
      Reaction Monitoring (SRM) assays for their unambiguous detection in biological
      samples. We used these assays to profile the frequency of the different types of
      inter-ubiquitin linkages in a mixture of in vitro assembled human poly-ubiquitin
      chains and 15 isolated poly-ubiquitinated proteins from S. cerevisiae. We then
      applied the method to detect toxin induced changes in the poly-ubiquitination
      profile in complex and enriched protein samples.

PMID- 20694218
TI  - The role of double hydrogen bonds in asymmetric direct aldol reactions catalyzed
      by amino amide derivatives.
AB  - The double hydrogen bonding activation of carbonyl functionality has been a
      general strategy for the design of amino amide organocatalysts for highly
      enantioselective direct aldol reactions of various ketones with aldehydes
      conducted in either organic solvents or aqueous media. Moreover, this concept may
      suggest an activation mode to create new catalysts for other related asymmetric
      transformations.

PMID- 20694219
TI  - Spectral and redox properties of zinc porphyrin core dendrimers with
      triarylamines as dendron.
AB  - The first and second generation of zinc porphyrin core dendrimers (3 and 4) with
      triarylamine as dendron have been synthesized via Ullmann coupling reaction.
      Their absorption and emission spectra indicate that there are strong interactions
      between zinc porphyrin core and triarylamine dendrons. Zinc porphyrin links with
      triarylamine causes Soret band broadening and Q band shift as compared with
      ZnTPP. Because of the antenna effect on these dendrimers, the fluorescence
      quantum yields were strongly enhanced when more triarylamine moieties were
      linked. Cyclic voltammetry and spectroelectrochemical methods were used to
      investigate the redox properties of dendrimers. Axial ligation of zinc porphyrin
      with N-methylimidazole is useful in differentiating the oxidation site of
      dendrimers. For the first generation dendrimer (3), porphyrin ring oxidation
      potential shifts cathodically because the periphery dendrons are strong electron
      donating groups. On the other hand, the dendrons of the second generation (4) are
      oxidized first and generate an atmosphere of eight positive charges. The
      porphyrin ring core is then oxidized with an anodic shift in potential due to the
      electron-withdrawing effect of the oxidized substituents.

PMID- 20694220
TI  - The role of metal ions and counterions in the switching behavior of a carboxylic
      acid functionalized spiropyran.
AB  - The ability of a carboxylic acid functionalized spiropyran, SP, to act as a
      reversible and selective receptor for metal ions has been systematically
      examined. A series of spectroscopic measurements, combined with single-crystal X
      ray diffraction have been employed in order to determine metal-ion sensitivity
      and selectivity, binding constants, solution compositions, binding kinetics as
      well as solid-state structure of a metal-complex of this ligand. This molecule
      acts as a chelating ligand and binds to metal ions using a triad of
      functionalities and will release the metal ion by application of visible light.
      Altering the complex from ZnCl(2) and Zn(ClO(4))(2), leads to only a small change
      in the complex absorption maxima from 494 to 492 nm, but produced a drastic
      increase in the sensitivity for the zinc(II) ion. Fluorescence spectroscopy was
      employed to establish that the detection limit for Zn(II) is approximately 3 x
      10(-7) M for Zn(ClO(4))(2). The counterion also influences binding constants and
      the equilibrium constants for Cu(ClO(4))(2) and CuCl(2) are K = 3.37 x 10(4) M(
      1) to K = 2.04 x 10(3) M(-1), respectively. Additionally, in the presence of
      perchlorate, the spiropyran-Cu complex formation is fast enough to allow for real
      time naked eye detection of this metal ion in less than three minutes; the
      formation of other metal complexes takes between 50 minutes to 2 hours. Finally,
      the single-crystal structure determination of the SP-zinc chloride complex shows
      that the Zn(II) ion displays a distorted square-pyramidal arrangement, and
      neighbouring metal ions are bound together into a 1-D coordination polymer with a
      hydrophilic core, surrounded by hydrophobic 'cladding'.

PMID- 20694221
TI  - Synthesis and characterization of enantiopure copper(II) complexes using chiral
      bidentate ligands.
AB  - Chiral copper(ii) complexes of the types [Cu(II)(R/S-ppme)(3)](ClO(4))(2) and
      [Cu(II)(R/S-ppme)(2)(SO(4))] have been synthesized by reactions of
      Cu(ClO(4))(2).6H(2)O and CuSO(4).5H(2)O with R/S-ppme in methanol under aerobic
      conditions (R/S-ppme = (R/S)-(+/-)-1-phenyl-N-(pyridine-2
      ylmethylene)ethanamine). All complexes were isolated and characterized by X-ray
      crystallography and circular dichroism (CD): (Lambda)-[Cu(II)(R
      ppme)(3)](ClO(4))(2) (1), (Delta)-[Cu(S-ppme)(3)](ClO(4))(2).H(2)O (2), (Delta)
      [Cu(II)(R-ppme)(2)(SO(4))].4CH(3)OH (3), and (Lambda)-[Cu(II)(S
      ppme)(2)(SO(4))].4CH(3)OH (4). 1 and 2 with ClO(4)(-) anions are formed as
      tris(R/S-ppme) copper(ii) complexes, while 3 and 4 with SO(4)(2-) are formed as
      bis(R/S-ppme) copper(ii) complexes. The structures of 1 with R-ppmes and 4 with S
      ppmes show the same absolute configurations (Lambda). In contrast, 2 with S-ppmes
      and 3 with R-ppmes exhibit Delta configurations. In the electron paramagnetic
      resonance (EPR) spectra of 1 and 3, both compounds demonstrate z-axis elongated
      structures. The CD spectra of 1 and 2 show Cotton effects in an enantiomeric
      pattern; those of 3 and 4 also display the same effects.

PMID- 20694222
TI  - Chiral sulfur derivatives in the allylation of acyl hydrazones: C(2)-symmetric
      bis-sulfinamides as enhanced chiral organic promoters.
AB  - Monosulfinamides and C(2)-symmetric bis-sulfinamides are convenient neutral
      chiral promoters in the allylation of acyl hydrazones, the nature of the spacer
      and the substituent at the sulfinyl sulfur are key elements for the
      enantioselectivity of the process.

PMID- 20694223
TI  - Rigid adamantane tripod linkage for well-defined conductance of a single-molecule
      junction.
AB  - We present a systematic analysis of molecular level alignments and electron
      transport characteristics based on the non-equilibrium Green's function (NEGF)
      approach combined with density functional theory (DFT) for phenyl dithiol (PDT)
      derivatives with two different linkages, simple thiol (ST) and tripod-shaped
      adamantane trithiol (ATT). The substantial adamantane-metal bonds afford a rigid
      contact structure and well-defined conductance of a single-molecule junction
      irrespective of interfacial phenomena, which accordingly allows us to utilize the
      intrinsic nature of the molecule for designing molecular devices with prescribed
      transport characteristics. We suggest a feasible application of the ATT linkage
      embedded single-molecule junction to a molecular transistor based on the
      practical feature of the ATT linkage, which is the unsusceptible behavior of
      transmission under the applied bias voltage. The present result may serve as an
      important reference point for designing molecular devices with prescribed
      transport properties.

PMID- 20694224
TI  - Discovering new block terpolymer micellar morphologies.
AB  - The self-assembly of a new type of triblock terpoly(2-oxazoline) was investigated
      in water revealing vesicular and aggregated cylindrical micellar structures.

PMID- 20694225
TI  - Measuring individual overpotentials in an operating solid-oxide electrochemical
      cell.
AB  - We use photo-electrons as a non-contact probe to measure local electrical
      potentials in a solid-oxide electrochemical cell. We characterize the cell in
      operando at near-ambient pressure using spatially-resolved X-ray photoemission
      spectroscopy. The overpotentials at the interfaces between the Ni and Pt
      electrodes and the yttria-stabilized zirconia (YSZ) electrolyte are directly
      measured. The method is validated using electrochemical impedance spectroscopy.
      Using the overpotentials, which characterize the cell's inefficiencies, we
      compare without ambiguity the electro-catalytic efficiencies of Ni and Pt,
      finding that on Ni H(2)O splitting proceeds more rapidly than H(2) oxidation,
      while on Pt, H(2) oxidation proceeds more rapidly than H(2)O splitting.

PMID- 20694226
TI  - Monitoring adsorption-induced switching by (129)Xe NMR spectroscopy in a new
      metal-organic framework Ni(2)(2,6-ndc)(2)(dabco).
AB  - The synthesis and structure of a new flexible metal-organic framework Ni(2)(2,6
      ndc)(2)(dabco) (DUT-8(Ni), DUT = Dresden University of Technology, 2,6-ndc = 2,6
      naphthalenedicarboxylate, dabco = 1,4-diazabicyclo[2.2.2]octane) as well as its
      characterization by gas adsorption and (129)Xe NMR spectroscopy is described. The
      compound shows reversible structural transformation without loss of crystallinity
      upon solvent removal and physisorption of several gases. Xenon adsorption studies
      combined with (129)Xe NMR spectroscopy turn out to be favorable methods for the
      detection and characterization of the so-called "gate-pressure" effect in this
      novel MOF material. The linewidth and chemical shift of the (129)Xe NMR signal
      are shown to be very sensitive parameters for the detection of this structural
      transition from a narrow pore system with low porosity to a wide pore state. The
      transition and threshold temperature is clearly detected.

PMID- 20694227
TI  - Micellar transitions in the aqueous solutions of a surfactant-like ionic liquid:
      1-butyl-3-methylimidazolium octylsulfate.
AB  - We have observed dual transitions in various physical properties while
      investigating the surfactant-like behavior of the ionic liquid (IL) 1-butyl-3
      methylimidazolium octylsulfate [C(4)mim][C(8)SO(4)] in aqueous media.
      Interestingly, in conductivity measurements, it was found that the second
      transition, which is comparatively weak in pure water, can be modulated and tuned
      to the desired concentration without affecting the first transition by the
      addition of a suitable electrolyte. Using an array of techniques, such as
      conductivity, ultrasonics, TEM, cryo-TEM, DLS, (1)H NMR and 2D (1)H-(1)H NOESY,
      it has been revealed that the first transition corresponds to the anionic
      aggregation with imidazolium cations adsorbed as counterions, and the second
      transition corresponds to the restructuring of the initially formed aggregates in
      a way that the alkyl chain of the imidazolium cation is incorporated towards the
      micellar core, leading to a unique mixed micelle-type structure in a single IL
      system.

PMID- 20694228
TI  - Pigments of fungi (macromycetes).

PMID- 20694229
TI  - Electrogenerated chemiluminescence from CdS hollow spheres composited with carbon
      nanofiber and its sensing application.
AB  - The electrogenerated chemiluminescence (ECL) from nanometre-sized CdS hollow
      spheres and carbon nanofiber (CdSHS-CNF) nanocomposites in aqueous solution and
      their sensing applications were studied by entrapping them in carbon paste. The
      CdSHS-CNF nanocomposites exhibited a peak at -1.02 V (vs. Ag/AgCl) in 0.1 M pH
      8.0 PBS containing 20 mM H(2)O(2) during the cyclic sweep between 0 and -1.2 V at
      40 mV s(-1). Compared with CdS hollow spheres (CdSHS), carbon nanofiber (CNF) and
      CdS nanocrystals and carbon nanofiber (CdSNC-CNF) nanocomposites, CdSHS-CNF not
      only enhanced the electrochemiluminescent intensity but also decreased the ECL
      starting potentials. Furthermore, by immobilizing cholesterol oxidase (ChOx) on
      CdSHS-CNF nanocomposites modified electrode, a sensitive and selective method was
      developed for detection of cholesterol using oxygen as a coreactant which
      captured more electrons from electrochemically reduced CdSHS-CNF than H(2)O(2).
      Under optimal conditions, the sensor could be used for the determination of
      cholesterol from 1 * 10(-6) to 4.4 * 10(-4) M with a correlation coefficient of
      0.9991 and a detection limit was 8 * 10(-7) M at 3sigma. The unique ECL intensity
      and stability of CdSHS-CNF would promote the application of nanometre-sized
      semiconductor hollow spheres based composites in fabricating sensors for chemical
      and biochemical analysis.

PMID- 20694230
TI  - Fluorescence resonance-energy-transfer in systems of Rhodamine 6G with ionic
      liquid showing emissions by excitation at wide wavelength areas.
AB  - Fluorescence resonance-energy-transfer occurred in a solution of Rhodamine 6G in
      an ionic liquid by excitation at wide wavelength areas owing to specific
      fluorescent behavior of the ionic liquid to show emissions at each excitation
      wavelength, which was also observed in the guar gum/ionic liquid gel material
      containing Rhodamine 6G.

PMID- 20694231
TI  - Caesium ion sequestration by a fluoro-metallocrown [16]-MC-8.
AB  - A fluoro-metallocrown selectively binds caesium, extracting it from aqueous
      solutions into an organic layer; the binding of Cs is monitored by (1)H-NMR of
      the paramagnetic complexes.

PMID- 20694232
TI  - Synthesis of double mesoporous core-shell silica nanospheres with radially
      oriented mesopores via one-templating step using anionic surfactant.
AB  - In this communication, we report the fabrication of silica nanospheres with a
      double mesoporous core-shell structure by a one-templating step two-pot synthesis
      route using an anionic surfactant.

PMID- 20694233
TI  - Photopolymerization of self-organizing ionic liquids.
AB  - In this article we describe the photo-initiated cyclopolymerization of N,N
      diallyl-N-dodecylammonium chloride and N,N-diallyl-N-hexadecylammonium chloride
      in aqueous lyotropic mesophases using a low power UVA domestic sunlamp to produce
      anisotropic polymers. We further demonstrate the formation of cross-linked
      anisotropic polymer networks upon the addition of 1,8-bis-(N,N
      diallylammonium)octane chloride.

PMID- 20694234
TI  - Dual stimuli-responsive interconvertible heteroleptic platinum coordination
      modes.
AB  - The exchange between different equilibrium and out-of-equilibrium platinum
      coordination modes can be orthogonally controlled thermodynamically with a proton
      input and kinetically using light.

PMID- 20694235
TI  - Au/SiO(2) core/shell nanoparticles enhancing fluorescence resonance energy
      transfer efficiency in solution.
AB  - Tailor-designed Au/SiO(2) core/shell nanoparticles are employed to enhance the
      efficiency of fluorescence resonance energy transfer based on quantum dots and R
      phycoerythrin in solution.

PMID- 20694236
TI  - Practical iron-catalyzed dehalogenation of aryl halides.
AB  - An operationally simple iron-catalyzed hydrodehalogenation of aryl halides has
      been developed with 1 mol% Fe(acac)(3) and commercial t-BuMgCl as reductant. The
      mild reaction conditions (THF, 0 degrees C, 1.5 h) effect rapid chemoselective
      dehalogenation of (hetero)aryl halides (I, Br, Cl) and tolerate F, Cl, OR, SR,
      CN, CO(2)R, and vinyl groups.

PMID- 20694237
TI  - N-heterocyclic carbene catalysed asymmetric cross-benzoin reactions of
      heteroaromatic aldehydes with trifluoromethyl ketones.
AB  - A new triazolium salt derived N-heterocyclic carbene catalyses an asymmetric
      cross-benzoin-type reaction of heteroaromatic aldehydes and various
      trifluoromethyl ketones in good to excellent yields (69-96%) and moderate to good
      enantioselectivities (ee = 39-85%). Up to 99% ee can be achieved by
      recrystallisation.

PMID- 20694238
TI  - Quantum-chemical study and FTIR jet spectroscopy of CHCl(3)-NH(3) association in
      the gas phase.
AB  - High level ab initio quantum chemical calculations have been performed on the
      association of chloroform with ammonia in the gas phase (counterpoise corrected
      MP2 and coupled-cluster CCSD(T) calculations with 6-311++G(d,p) basis functions).
      Minimum energy equilibrium structures have been found for CHCl(3)-NH(3) dimer,
      CHCl(3)-(NH(3))(2) trimer and CHCl(3)-(NH(3))(3) tetramer. Association is
      characterised by a CHN hydrogen bond between a chloroform and an ammonia
      molecule, with further ammonia units attached by hydrogen bonds to ammonia and by
      an electrostatic NHCl interaction to chloroform. Cooperative effects provide
      additional stabilisation. The complexes exhibit characteristic shifts of
      vibrational bands and change of IR intensity; in particular there is a pronounced
      progressive shift of the CH-stretching vibration towards lower wavenumber with
      each unit of ammonia attached in the complex. The shift is accompanied by an up
      to 600 fold increase in IR intensity. The experimental FTIR jet spectra have
      provided firm evidence of CHCl(3)-NH(3) association, with the clearest effects
      seen in the region of the CH-stretching vibration. First tentative assignments
      have been made based on the dependence of relative intensities of cluster
      features on the concentration of monomers, and assignments have been corroborated
      by the quantum chemical calculations. The present combined ab initio and FTIR
      spectroscopy study reveals the structure and energetics of cluster formation and
      intermolecular bonding in CHCl(3)-NH(3) association.

PMID- 20694239
TI  - Interpenetrating icosahedra chains based zinc-rich ternary phases
      Ru4.0Sn2.9Zn11.6 and Ru3.0Sb0.97Zn11.0: synthesis, structures and physical
      properties.
AB  - Substituting of Ru with Sn and Sb in the phase RuZn(3) led to two new zinc-rich
      ternary compounds: Ru(4)Sn(2.9)Zn(11.6) (SnRZ: Monoclinic, C2/m, Pearson symbol
      oC46-delta, a = 6.8011(14), b = 7.9760(16), c = 11.083(2) A, beta = 97.56(3)
      degrees, Z = 2) and Ru(3.0)Sb(0.97)Zn(11.0) (SbRZ: Orthorhombic, Cmcm, Pearson
      symbol oC60, a = 7.8936(16), b = 6.8347(14), c = 16.904(3) A, Z = 4). The
      structures of SnRZ and SbRZ are composed of four identical atomic layers but with
      different stacking sequences. They exhibit structural units of either three or
      two interpenetrating icosahedra fusing to form chains along the c axis. Their a
      and b lattice parameters are alike-interchanged in the chosen conventional
      setting-while the c parameters are related by c(SbRZ)/2 x (1 + tau) approximately
      = 2c(SnRZ) with tau = (1 + square root(5))/2 being the golden mean (known as tau
      inflated phases). Both two compounds exhibit diamagnetic properties, and SnRZ and
      SbRZ congruently melt at 1296 K and 1233 K, respectively. Temperature-dependent
      resistivities reveal metallic behavior. The negative Seebeck coefficients
      indicate transport processes are dominated by electrons as carriers.

PMID- 20694240
TI  - A sensitive phosphorescent thiol chemosensor based on an iridium(III) complex
      with alpha,beta-unsaturated ketone functionalized 2,2'-bipyridyl ligand.
AB  - An iridium(III)-containing phosphorescent chemosensor Ir(ppy)(2)(L)(PF(6)) (1,
      ppy = 2-phenylpyridine) containing a 2,2'-bipyridyl ligand (L) functionalized
      with an alpha,beta-unsaturated ketone for selective detection of thiol was
      synthesized and characterized by spectroscopic and photophysical measurements.
      The structure of complex 1 was determined by X-ray crystallography. In order to
      get an insight into 1,4-addition reactions of thiol to complex 1, the adduct 2
      from reaction of 1 with benzenethiol was successfully prepared and characterized.
      Complex 1 shows a lowest energy absorption at ca. 450 nm, primarily ascribable to
      an intraligand charge transfer (ILCT) transition from the HOMO (pi) resident on
      the fragment -C(O)C(6)H(4)N(C(2)H(5))(2) to the LUMO (pi*) localized on the 2,2'
      bipyridyl moiety in the functionalized 2,2'-bipyridyl ligand as suggested from
      DFT computational studies. Complex 1 is weakly emissive at ca. 587 nm at ambient
      temperature, arising likely from the (3)ILCT excited state. Upon addition of
      thiol to a semi-aqueous solution of complex 1, the lowest energy absorption is
      obviously blue-shifted and the emission is remarkably enhanced due probably to a
      conversion from the primary ILCT state to the predominant [pi(ppy)-->pi*(L)] LLCT
      and the [5d(Ir)-->pi*(L)] MLCT state caused by the formation of the 1-thiol
      adduct. The sensing properties of 1 to thiol were also investigated by ESI-MS
      spectrometry and (1)H NMR spectroscopy.

PMID- 20694241
TI  - Hydrothermal syntheses, crystal structures and physicochemical properties of 2-D
      and 3-D inorganic coordination cobalt(II)-sulfite polymers.
AB  - The hydrothermal reaction of [Co(III)(NH(3))(6)]Cl(3) with Na(2)SO(3) yields,
      depending on the concentration of Na(2)SO(3), compounds
      {Na[Co(II)(2)(SO(3))(2)(mu(3)-OH)(H(2)O)]}(infinity) (1) and
      {Na(4)[Co(II)(2)(SO(3))(4)]}(infinity) (2). When (NH(4))(2)SO(3) x H(2)O was
      substituted for Na(2)SO(3), the trinuclear mixed valence cobalt(II/III) complex
      (NH(4))(4){Co(II)[Co(III)(SO(3))(3)(NH(3))(3)](2)} x 2H(2)O (3 x 2H(2)O) was
      isolated. The cobalt-sulfites 1-3 x 2H(2)O were structurally characterized. In 1,
      the 1-D chains along the a-axis of the subunit
      [Co(II)(2)Co(II)(3)(OH)(2)(SO(3))(2)] are cross-linked with Co(II)(1) atoms via
      Co-O(sulfite) and Co-O(hydroxide) bonds in 2-D sheets, that are further stacked
      through interlayer hydrogen bonds. In 2, the [Co(II)(2)(SO(3))(2)](infinity)
      chains along the b-axis are cross-linked with tetrahedral cobalts via Co(II)
      O(sulfite) bonds in 2-D sheets parallel to the ab-plane and the sheets are
      further bound to sodium atoms via Na(+)-O(sulfite) bonds to form a 3-D structure.
      The 3-D inorganic coordination polymer, 2, crystallizes in the non
      centrosymmetric space group P2(1)2(1)2(1). In addition, in compound 2 octahedral
      and tetrahedral cobalt atoms coexist, which is rather unusual for cobalt
      clusters. Compound 3 x 2H(2)O is a 0-D mixed-valence {[(NH(3))(3)Co(III)(mu
      SO(3))(3)]Co(II)[(mu-SO(3))(3)Co(III)(NH(3))(3)]}(4-) trinuclear cluster and can
      be considered as an octahedral {Co(II)O(6)} complex ligated to two tridentate
      [(NH(3))(3)Co(III)(SO(3))(3)](3-) ligands. The trinuclear clusters are stacked
      through an extended network of hydrogen bonding into a 3-D structure. Variable
      temperature magnetic susceptibility studies for 1-3 x 2H(2)O revealed that 1 and
      2 are 2-D magnetic systems with strong antiferromagnetic interaction between the
      Co(II) atoms leading to an S = 0 ground state for 1, while in compound 2 there is
      an almost zero interaction between the cobalt(II) atoms leading to a non-zero
      ground state. The trinuclear compound 3 x 2H(2)O has two diamagnetic Co(III)
      atoms and a high-spin Co(II) atom with D = 84(1) cm(-1), E = 6(1) cm(-1) and g =
      2.56(1). The IR, the solid-state UV-vis spectra and the thermogravimetric
      analyses of compounds 1-3 x 2H(2)O are also reported.

PMID- 20694242
TI  - Single chain versus single aggregate spectroscopy of conjugated polymers. Where
      is the border?
AB  - Single chains of conjugated polymers e.g. MEH-PPV (poly(2-methoxy-5-(2'
      ethylhexyloxy)-1,4-phenylenevinylene) have become interesting objects for single
      molecule spectroscopy (SMS) studies. However, most of the experiments so far were
      performed without full awareness of the isolation status of the polymer chains in
      host matrices. We used steady-state and time-resolved fluorescence methods and 2D
      polarization single molecule imaging technique to unravel the
      isolation/aggregation status of MEH-PPV in spin-coated films prepared at
      different conditions. It turned out that a sample showing isolated bright spots
      in fluorescence images could be obtained in a very broad concentration range of
      MEH-PPV when toluene was used as a solvent and PMMA as a matrix. If the MEH-PPV
      concentration was not sufficiently low, a substantial fraction of the
      fluorescence spots should be assigned to individual nano-aggregates rather than
      truly isolated chains of the polymer. Contrary to single aggregates, truly
      isolated MEH-PPV chains showed blue-shifted emission spectra, mono-exponential
      fluorescence decay dynamics with relatively long lifetimes (0.4-1.2 ns), and high
      polarization anisotropy. We argue that insufficient control of the concentration
      in the published SMS studies of MEH-PPV resulted in incorrect assigning of some
      spectroscopic properties of single aggregates to isolated MEH-PPV chains. We
      believe this to be the main origin of discrepancies among the published data in
      this field.

PMID- 20694243
TI  - Benzoyl peroxide (BPO)-promoted oxidative trifluoromethylation of tertiary amines
      with trimethyl(trifluoromethyl)silane.
AB  - The benzoyl peroxide (BPO)-promoted oxidative functionalization of tertiary
      amines under transition-metal-free reaction conditions was developed. Various 1
      trifluoromethylated tetrahydroisoquinoline derivatives were prepared by employing
      this method. It constitutes the first example of direct trifluoromethylation of
      tertiary amines.

PMID- 20694244
TI  - Low-bandgap conjugated polymer for high efficient photovoltaic applications.
AB  - We investigate the morphological and performance of organic photovoltaics based
      on blended films of alternating poly(thiophene-phenylene-thiophene) and [6,6]
      phenyl-C(71)-butyric acid methyl ester (PC(71)BM). The resulting fine-scale phase
      separation leads to enhanced performance and the highest power efficiency (6.4%
      under AM 1.5G (100 mW cm(-2))) when we use solvent annealing process.

PMID- 20694245
TI  - An electroswitchable fluorescence thin-film based on a luminescent
      polyoxometalate cluster.
AB  - We selected a Eu(3+)-containing tungstogermanate
      [(CH(3))(4)N](2.5)H(7.5)[Eu(GeW(11)O(39))(H(2)O)(2)](2).4.5H(2)O (EuGeW) as a
      molecular dyad combining fluorescence and electroactivity components within the
      same framework and studied its electroswitchable fluorescence in solution and in
      the thin-film, which can be reversibly switched by electrochemical stimulation.

PMID- 20694246
TI  - Templating molecular adsorption using a covalent organic framework.
AB  - A two-dimensional nanoporous covalent organic framework can be prepared on a
      Au(111) substrate with near complete surface coverage and can be used to control
      the organisation of a sublimed layer of C(60).

PMID- 20694248
TI  - Thermodynamic evidence for K(+)-SO4(2-) ion pair formation on Pt(111). New
      insight into cation specific adsorption.
AB  - This work contributes to the understanding of cation specific effects on platinum
      electrochemistry by means of a thorough thermodynamic analysis of potassium
      adsorption on Pt(111) in sulfuric acid solutions. It is concluded that potassium
      specific adsorption is better described as the adsorption of the K(+)-SO ion
      pair. From the evaluation of the potassium sulfate concentration, it is found
      that potassium specific adsorption only takes place in the presence of coadsorbed
      sulfate species. Within the main sulfate adsorption state, for ~0.3 V < E < ~0.4
      V (vs. SHE), the extent of potassium specific adsorption is small, reaching ~0.1
      * 10(14) species per cm(2) for c(K(+)) > 0.1 M. Then, at higher potentials, E >
      0.55 V (vs. SHE), a second potassium adsorption process takes place, concomitant
      with the second sulfate adsorption process (associated to the small voltammetric
      feature called "the hump"). This last process involves the adsorption of an equal
      amount of potassium and sulfate species, leading to the adsorption of ~0.5 *
      10(14) ion pair species per cm(2) (~0.03 ion pair species per platinum surface
      atom). Furthermore, the results of the formal partial charge numbers corroborate
      that potassium adsorption involves sulfate cooperative coadsorption, in such a
      way that the effective adsorbing species is anionic, rather than cationic. In
      conclusion, this work evidences that cation specific effects may originate from
      the formation of surface ion pairs, which is probably related to the presence of
      ion pairs in solution.

PMID- 20694247
TI  - Lithographically-featured photonic microparticles of colloidal assemblies.
AB  - We have described a new and promising strategy for the fabrication of composite
      and porous photonic crystal microparticles that combines the self-assembly of
      colloidal particles with photolithography techniques. We fabricated silica/SU-8
      composite microparticles with photonic bandgaps via four steps: (1) deposition of
      the silica colloidal crystals on the photoresist, (2) embedding of the colloidal
      crystals in the photoresist, (3) UV exposure through a photomask and subsequent
      development, and (4) release of the microparticles from the substrate. Embedding
      was performed above the glass transition temperature (T(g)) of uncrosslinked SU
      8. At such temperatures, capillary forces on the silica particles facilitate the
      migration of colloidal crystals in the SU-8 matrix. Particle migration ceased
      when the top colloidal crystal layer was trapped at the interface between air and
      SU-8. In addition, we also prepared porous microparticles with an inverse opaline
      structure by dissolving the embedded silica particles from the composite
      structures. The porous microparticles showed enhanced reflectivity at the bandgap
      position due to the large refractive index contrast. The bandgap position of the
      microparticles was controlled by the size of the silica particles, which
      determined the lattice constant. Bilayered composite and porous microparticles
      with two distinct photonic bandgaps were also prepared by sequential deposition
      of colloidal crystals composed of two differently sized silica particles.

PMID- 20694249
TI  - Self-assembled monolayers of perfluoroterphenyl-substituted alkanethiols:
      specific characteristics and odd-even effects.
AB  - Self-assembled monolayers (SAMs) formed by perfluoroterphenyl-substituted
      alkanethiols (C(6)F(5)-C(6)F(4)-C(6)F(4)-(CH(2))(n)-SH, FTPn) with variable
      length of the aliphatic linker (n = 2 and 3) were prepared on (111) Au and Ag and
      characterized by a combination of several complementary spectroscopic and
      microscopic techniques. A specific feature of these systems is the helical
      conformation of the FTP moieties, which, along with the high electronegativity of
      fluorine, distinguishes them from the analogous non-fluorinated systems and makes
      them attractive for different applications. The SAMs were found to be well
      defined, highly ordered, and densely packed, which suggests a perfect correlation
      between the orientations and, in particular, twists of the FTP helices in the
      adjacent molecules. Significantly, the SAM exhibited pronounced odd-even effects,
      i.e. a dependence of the molecular orientation and packing density on the length
      of the aliphatic linker in the target molecules, with parity of n being the
      decisive parameter and the direction of the effects on Au opposite to that on Ag.
      The presence of the odd-even effects in the FTPn system brings new aspects into
      the discussion about the origin and mechanism of these phenomena. Specifically,
      the helical conformation of the FTP moieties in the dense phase excludes a
      variation of the intramolecular torsion and molecular twist as the mechanism
      behind the odd-even effects.

PMID- 20694250
TI  - (CH3)3COOH (tert-butyl hydroperoxide): OH reaction rate coefficients between 206
      and 375 K and the OH photolysis quantum yield at 248 nm.
AB  - Rate coefficients, k, for the gas-phase reaction of the OH radical with
      (CH(3))(3)COOH (tert-butyl hydroperoxide) were measured as a function of
      temperature (206-375 K) and pressure (25-200 Torr (He, N(2))). Rate coefficients
      were measured under pseudo-first-order conditions using pulsed laser photolysis
      to produce OH and laser induced fluorescence (PLP-LIF) to measure the OH temporal
      profile. Two independent methods were used to determine the gas-phase infrared
      cross sections of (CH(3))(3)COOH, absolute pressure and chemical titration, that
      were used to determine the (CH(3))(3)COOH concentration in the LIF reactor. The
      temperature dependence of the rate coefficients is described, within the
      measurement precision, by the Arrhenius expression k(1)(T) = (7.0 +/- 1.0) * 10(
      13) exp[(485 +/- 20)/T] cm(3) molecule(-1) s(-1) where k(1)(296 K) was measured
      to be (3.58 +/- 0.54) * 10(-12) cm(3) molecule(-1) s(-1). The uncertainties are
      2sigma (95% confidence level) and include estimated systematic errors. UV
      absorption cross sections of (CH(3))(3)COOH were determined at 185, 214, 228, and
      254 nm and over the wavelength range 210-300 nm. The OH quantum yield following
      the 248 nm pulsed laser photolysis of (CH(3))(3)COOH was measured relative to the
      OH quantum yields of H(2)O(2) and HNO(3) using PLP-LIF and found to be near
      unity.

PMID- 20694251
TI  - Primary 1,2-diamine catalysis III: an unexpected domino reaction for the
      synthesis of multisubstituted cyclohexa-1,3-dienamines.
AB  - The first organocatalyzed multicomponent domino reactions of aryl ketones,
      aldehydes and malononitrile were carried out successfully to afford
      multisubstituted cyclohexa-1,3-dienamines in satisfactory yields.

PMID- 20694252
TI  - An improved method to measure the rate of vaporisation and thermal decomposition
      of high boiling organic and ionic liquids by thermogravimetrical analysis.
AB  - The vapour pressure and the thermal stability of liquids are important material
      properties. For high boiling organic and ionic liquids (ILs), the determination
      of these properties is laborious and it is not easy to discriminate between
      evaporation and thermal decomposition. In this work, a simple but accurate method
      is presented to determine the parameters of decomposition and evaporation by
      thermogravimetrical analysis (TGA). The mass transfer coefficient was calculated
      based on a new correlation for the Sherwood number for cylindrical crucibles in
      overflow of a carrier gas. This correlation is valid for any diameter-to-height
      ratio and for any filling degree of the crucible and was derived from numerical
      simulations and proven by experiments with hexadecane, dodecane, and anthracene.
      The TGA analysis of two ILs was conducted. [EMIM][EtSO(4)] decomposes at ambient
      pressure without a measurable contribution of evaporation. To the contrary,
      [BMIM][NTf(2)] is relatively volatile. The vapour pressure of [BMIM][NTf(2)] and
      the kinetics of decomposition of both ILs were determined.

PMID- 20694253
TI  - Differences between the macroscopic and tracer level chemistry of rhenium and
      technetium: contrasting cage isomerisation behaviour of Re(I) and Tc(I) carborane
      complexes.
AB  - Carboranes form stable complexes with the [M(CO)(3)](+) (M = (99m)Tc, Re) core
      and are viable ligands for the development of targeted radiopharmaceuticals.
      (99m)Tc-carborane complexes were found to exhibit substantially different 1,2-
      >1,7 cage isomerisation behaviour than their Re counterparts, challenging the
      validity of the routine use of rhenium as a surrogate for the development of
      technetium-99m based molecular imaging agents.

PMID- 20694254
TI  - Cluster control in oligouranyl complexes of p-t-butylcalix[8]arene.
AB  - Formation of uranyl ion complexes of p-t-butylcalix[8]arene by reaction of the
      calixarene with [UO(2)(dmso)(5)](2+) in the presence of various bases leads to
      the crystallisation of solids with interestingly different stoichiometry,
      involving both di- and tri-uranate oligomers bound to the calixarene in anionic
      species. In all, the calixarene hexa-anion is present in a virtually identical
      conformation, suggesting that conformational preferences of the ligand must be a
      major factor controlling the form of the bound oxo-metal complex. Hydrogen
      bonding to the anions does not appear to be prominent even in the presence of
      protonated amines and this may explain the formation of some remarkable
      cation/solvent/simple anion clusters found within the lattices.

PMID- 20694255
TI  - Detection of waterborne parasites using field-portable and cost-effective
      lensfree microscopy.
AB  - Protection of human health and well-being through water quality management is an
      important goal for both the developed and the developing parts of the world. In
      the meantime, insufficient disinfection techniques still fail to eliminate
      pathogenic contaminants in freshwater as well as recreational water resources.
      Therefore, there is a significant need for screening of water quality to prevent
      waterborne outbreaks and incidents of water-related diseases. Toward this end,
      here we investigate the use of a field-portable and cost-effective lensfree
      holographic microscope to image and detect pathogenic protozoan parasites such as
      Giardia Lamblia and Cryptosporidium Parvum at low concentration levels. This
      compact lensless microscope (O. Mudanyali et al., Lab Chip, 2010, 10, 1417-1428),
      weighing approximately 46 grams, achieves a numerical aperture of approximately
      0.1-0.2 over an imaging field of view that is more than an order of magnitude
      larger than a typical 10X objective lens, and therefore may provide an important
      high-throughput analysis tool for combating waterborne diseases especially in
      resource limited settings.

PMID- 20694256
TI  - An automated, high-throughput experimental system for induced charge
      electrokinetics.
AB  - Recent experiments in induced charge electrokinetics (ICEK) have shown that the
      standard theory generally overpredicts experimentally observed velocities. Such
      discrepancies reduce the efficacy of practical ICEK devices, and highlight our
      incomplete understanding of electrokinetic phenomena. Here, we present an
      automated experimental system that allows for the rapid collection of ICEK data
      under a variety of conditions ( approximately 1000 per day) to help develop and
      constrain new theories. We demonstrate this system by studying the ICEK slip
      flows over electrodes that have been controllably "contaminated" with a
      dielectric layer, either SiO(2) or an alkanethiol self-assembled monolayer, of
      known thickness. We also develop a theory that accounts for the effects of the
      dielectric coatings surface chemistry that yields quantitative agreement with
      experiments over nearly a thousand distinct conditions in the SiO(2) system and
      present an additional three thousand experiments of flows over alkanethiol
      monolayers. Our experimental system allows the direct interrogation of the
      physico-chemical effects that influence ICEK flows and for the optimization of
      these flows in lab-on-a-chip systems.

PMID- 20694257
TI  - Stacking interaction in the middle and at the end of a DNA helix studied with non
      natural nucleotides.
AB  - Base stacking is important for the base pair interaction of a DNA duplex, DNA
      replication by polymerases, and single-stranded nucleotide overhangs. To study
      the mechanisms responsible for DNA stacking interactions, we measured the thermal
      stability of DNA duplexes containing a non-natural nucleotide tethered to a
      simple aromatic hydrocarbon group devoid of dipole moments and hydrogen bonding
      sites. The duplexes containing tetrahydrofuran were paired with a deoxyadenosine
      derivative (A/T base pair analog) or a deoxycytidine derivative (C/G base pair
      analog) and showed a lower stability than Watson-Crick base pairing, partly due
      to the loss of interbase hydrogen bonds. Conversely, non-natural nucleotides
      present at a dangling end yielded an interaction energy as high as that observed
      with base pairing. Importantly, the non-natural nucleotides yielded an
      interaction energy with a linear correlation similar to that of the analogous
      Watson-Crick base pairs both in the middle and at the end of a DNA duplex,
      although a different stacking mechanism between the middle and the end was
      suggested. Moreover, a positive cooperativity was observed in dangling end
      stacking of the nucleotide base moiety and aromatic hydrocarbon group. These
      observations are useful to understand nucleic acid interactions and to design new
      non-natural nucleotides.

PMID- 20694258
TI  - DNA as supramolecular scaffold for functional molecules: progress in DNA
      nanotechnology.
AB  - Oligonucleotides have recently gained increased attraction as a supramolecular
      scaffold for the design and synthesis of functional molecules on the nanometre
      scale. This tutorial review focuses on the recent progress in this highly active
      field of research with an emphasis on covalent modifications of DNA; non-covalent
      interactions of DNA with molecules such as groove binders or intercalators are
      not part of this review. Both terminal and internal modifications are covered,
      and the various points of attachment (nucleobase, sugar moiety or phosphodiester
      backbone) are compared. Using selected examples of the recent literature, the
      diversity of the functionalities that have been incorporated into DNA strands is
      discussed.

PMID- 20694259
TI  - The role of porphyrin chemistry in tumor imaging and photodynamic therapy.
AB  - In recent years several review articles and books have been published on the use
      of porphyrin-based compounds in photodynamic therapy (PDT). This critical review
      is focused on (i) the basic concept of PDT, (ii) advantages of long-wavelength
      absorbing photosensitizers (PS), (iii) a brief discussion on recent advances in
      developing PDT agents, and (iv) the various synthetic strategies designed at the
      Roswell Park Cancer Institute, Buffalo, for developing highly effective long
      wavelength PDT agents and their utility in constructing the conjugates with tumor
      imaging and therapeutic potential (Theranostics). The clinical status of certain
      selected PDT agents is also summarized (205 references).

PMID- 20694260
TI  - On the atomic structure of thiol-protected gold nanoparticles: a combined
      experimental and theoretical study.
AB  - In the present work new findings on the structure of the S-Au interface are
      presented. Theoretical calculations using a new semiempirical potential, based on
      density functional theory and a bond-order Morse potential, are employed to
      simulate the adsorption process in a more realistic way. The simulation results
      reveal the formation of gold adatoms on the nanoparticle surface and high surface
      disorder due to the strong S-Au bond. Experimental data were acquired by
      aberration (Cs) corrected scanning transmission electron microscopy (STEM) using
      a high angle annular dark field detector (HAADF) that showed a great similarity
      with the theory predicted.

PMID- 20694261
TI  - High hydrostatic pressure-induced conformational changes in protein disulfide
      oxidoreductase from the hyperthermophilic archaeon Pyrococcus furiosus. A Fourier
      transform infrared spectroscopic study.
AB  - Protein disulfide oxidoreductases (PDOs) are ubiquitous redox enzymes that
      catalyse dithiol-disulfide exchange reactions. PDOs have been well studied in
      bacteria and eukarya, and they have been described in a number of thermophilic
      and hyperthermophilic species, where they play a critical role in the structural
      stabilization of intracellular proteins. In this study, the effect of high
      hydrostatic pressure on the structural properties of PDO from the
      hyperthermophilic archaeon Pyrococcus furiosus (PfPDO) was analysed in order to
      gain insights on the possible mechanisms used to endure extreme environmental
      conditions. The protein is highly thermostable and the data indicate that PfPDO
      is highly piezostable as well, and that different areas of the protein have a
      different local compressibility and resistance to high hydrostatic pressure. In
      particular, the results show that alpha-helices are more sensitive to pressure up
      to 5 kbar, whilst within 5-9 kbar the loss of beta-sheets is more pronounced than
      the loss of alpha-helices. Examination of the PfPDO structure and calculations of
      the solvent accessible surface areas for each amino acid indicate that 42% of the
      PfPDO residues are buried and that the protein contains four small internal
      hydrophobic cavities. These findings are discussed in terms of important factors
      contributing to the high piezostability and thermostability of the enzyme.

PMID- 20694263
TI  - CoCoCo: a free suite of multiconformational chemical databases for high
      throughput virtual screening purposes.
AB  - In the last few decades, virtual screening has proved to be able to guide the
      selection of new hit compounds with predefined biological activity. However, the
      usage of these computational techniques is often associated with resource- and
      time-consuming preparation protocols. In this work we present Commercial Compound
      Collection (CoCoCo), a suite of free and ready-to-use chemical databases to help
      setting up in silico screening projects. CoCoCo collects molecular structural
      information of commercial compounds from various chemical vendors by merging them
      in a unique, non-redundant format. CoCoCo databases are prepared with transparent
      and straightforward routines based on state-of-the-art computational tools that
      introduce comprehensive structural information about tautomers, stereoisomers and
      conformational states of each compound. CoCoCo suite is especially conceived as a
      set of valuable tools that may help a wide range of researchers who wish to
      initiate their own project in the field of computational drug design. CoCoCo
      suite is available free of charge at the website .

PMID- 20694264
TI  - Lipo-oligoarginines as effective delivery vectors to promote cellular uptake.
AB  - An effective cellular delivery vector with enhanced intracellular retention was
      developed by conjugating a cell-penetrating peptide (CPP) with a fatty acid
      chain. The optimized lipopeptide (LP), myristoylated hendecaarginine (C14R11),
      penetrated the cell membrane with high efficiency, and achieved superior
      metabolic stability and versatility as compared with unmodified oligoarginine
      CPPs, offering no adverse effect on cell viability and function. Cellular uptake,
      intracellular localization, cytotoxicity, and release kinetics of oligoarginines
      and LPs were investigated using flow cytometry analysis, cytotoxicity assay, and
      confocal microscopy. The cellular uptake efficiency and intracellular metabolic
      stability of C14R11 LP was further enhanced by replacing the L-arginine residues
      with D-arginine isomers. The cellular uptake and intracellular metabolic
      stability of D-form C14R11 (C14dR11) was significantly increased without any
      noticeable cytotoxicity compared to the unmodified parent hepta-arginine CPP or L
      arginine LPs.

PMID- 20694265
TI  - Reversible photoswitching of protein function.
AB  - Using light to tune the activity of proteins represents a very attractive avenue
      for creating various temporal interferences in living systems. In this mini
      review, we highlight a few recent developments in this broad and exciting field.
      Among the various methods, we have discussed in more detail the advantages and
      future challenges in using light switchable drugs to regulate the signaling
      proteins in the immune system.

PMID- 20694267
TI  - Improving the compatibility of fullerene acceptors with fluorene-containing donor
      polymers in organic photovoltaic devices.
AB  - Fluorene-containing PCBM analogs have been synthesized and tested with a
      polyfluorene copolymer, PF10TBT, in organic photovoltaic devices resulting in an
      increase of ~130 mV in the open circuit voltage compared to devices with PCBM as
      acceptor material.

PMID- 20694266
TI  - Excursions in polynuclear platinum DNA binding.
AB  - Polynuclear platinum agents are a structurally unique class of anti-cancer drugs,
      distinct from the cisplatin family. To describe the chemistry and biology of this
      class, it was necessary to challenge the accepted paradigms for the structure
      activity relationships; design new chemotypes and delineate the structures and
      consequences of their DNA binding modes. This article summarizes the structural
      changes induced in DNA by both covalent (bond-forming) and non-covalent (ligand
      recognition) adducts. Solution (Nuclear Magnetic Resonance), solid state
      (crystallography) and gas-phase (Electrospray Ionization Mass Spectrometry)
      techniques have all been used to describe the new DNA structures along with
      molecular biological techniques. The combined approaches allow molecular
      description of hitherto unobserved adducts such as long-range major-groove
      interstrand crosslinks; directional isomers on DNA and a third class of ligand
      DNA binding, the phosphate clamp. The phosphate recognition is distinct from
      ''classic'' minor-groove recognition or intercalation.

PMID- 20694268
TI  - Preparation of supported Mo(2)C-based catalysts from organic-inorganic hybrid
      precursor for hydrogen production from methanol decomposition.
AB  - An effective and safe route is proposed to prepare supported Mo(2)C-based
      catalysts from organic-inorganic hybrids, which exhibit high activity and
      stability for producing H(2) from methanol catalytic decomposition.

PMID- 20694269
TI  - Single-cell detection using a thin film transistor photosensor with micro
      partitions.
AB  - A thin film transistor (TFT) photosensor was applied to single-cell detection by
      identifying cell surface molecules based on chemiluminescence. Micro-partitions
      were directly fabricated on the TFT photosensor surface by photolithography. The
      surface of each pixel was surrounded by 25 MUm-height partitions, forming areas
      of approximately 30 MUm * 30 MUm for cell entrapment and photosensing.
      Visualization of individual JM cells, stained with mouse anti-human CD8 IgG1
      primary antibody and Horseradish peroxidase (HRP)-labeled anti-mouse IgG1
      secondary antibody, as bright-pixels was successfully achieved using the micro
      partitioned TFT photosensor integrated into a microfluidic chamber. Furthermore,
      real-time monitoring of HRP-labeled JM cells was also accomplished. The
      fabrication of micro-partitions on the surface of the TFT photosensor allows
      highly efficient single-cell entrapment and chemiluminescence-based detection of
      JM cells. This is the first report of single-cell entrapment and subsequent
      signal detection on the photosensing area of individual pixels of TFT
      photosensor. This system will allow high-throughput and real-time analysis of
      more than 10(4) cells with minimum optical system requirements.

PMID- 20694270
TI  - Splitting of beta-carotene in the sexual interaction of Phycomyces.
AB  - Two new 7-carbon compounds, 1 and 2, have been found in the culture medium of
      Phycomyces blakesleeanus. A genetic test showed that they derive from beta
      carotene. These new molecules represent the missing link that proves that beta
      carotene is split into fragments of 18, 15 and 7 carbon fragments, each head of a
      separate family of apocarotenoids.

PMID- 20694271
TI  - Substitution position effect on photoluminescence emission and chain conformation
      of poly(diphenylacetylene) derivatives.
AB  - The significant variation in photoluminescence emission of
      poly(diphenylacetylene) derivatives according to the substitution position is due
      to the differences in the intramolecular pi-stack structure and chain
      conformation.

PMID- 20694272
TI  - Terephthalate as a probe for photochemically generated hydroxyl radical.
AB  - Hydroxyl radical ( OH) production in sunlit natural waters is known to be an
      important factor in pollutant degradation and nutrient cycling, and various
      probes have been developed to study this species in aquatic systems. Many of
      these probes have limitations in sensitivity and/or selectivity for OH, leaving
      room for improvement. Terephthalate (TPA) is a known probe for OH that produces a
      fluorescent product, hydroxyterephthalate (hTPA), upon hydroxylation, but its
      suitability for studying photochemical OH production has not been fully tested.
      To that end, the photochemical behavior of TPA and hTPA was characterized. TPA
      and hTPA react with OH with rate constants of (4.4 +/- 0.1) x 10(9) M(-1) s(-1)
      and (6.3 +/- 0.1) x 10(9) M(-1) s(-1), respectively. They were found to react
      with singlet oxygen ((1)O(2)) with significantly lower rate constants of <<10(4)
      M(-1) s(-1) and (5.0 +/- 0.1) x 10(4) M(-1) s(-1), respectively, indicating that
      TPA is selective for OH versus(1)O(2). TPA did not undergo direct photolysis,
      while hTPA was shown to undergo direct photochemical degradation with a
      Phi(direct,365nm) of (6.3 +/- 0.1) x 10(-3). TPA was applied to monitoring
      photochemical OH production by nitrate, nitrite and dissolved organic matter
      (DOM), and OH quenching rate constants measured for DOM were similar to results
      from previous studies. TPA provides a stable and sensitive probe for OH under
      significantly shorter photo-exposure times than similarly structured probe
      molecules, such as benzoate. However, the photoinstability of the analyte, hTPA,
      makes TPA an unsuitable probe for the study of photochemical systems under
      ultraviolet irradiation with wavelengths shorter than 360 nm.

PMID- 20694273
TI  - Randomised, parallel-group, multicentre, multinational phase 2 study comparing
      edoxaban, an oral factor Xa inhibitor, with warfarin for stroke prevention in
      patients with atrial fibrillation.
AB  - The primary objective of this study was to compare the safety of four fixed-dose
      regimens of edoxaban with warfarin in patients with non-valvular atrial
      fibrillation (AF). In this 12-week, parallel-group, multicentre, multinational
      study, 1,146 patients with AF and risk of stroke were randomised to edoxaban 30
      mg qd, 30 mg bid, 60 mg qd, or 60 mg bid or warfarin dose-adjusted to a target
      international normalised ratio of 2.0-3.0. The study was double-blind to edoxaban
      dose, but open-label to warfarin. Primary outcomes were occurrence of major
      and/or clinically relevant non-major bleeding and elevated hepatic enzymes and/or
      bilirubin. Mean age was 65 +/- 8.7 years and 64.4% were warfarin-naive. Whereas
      major plus clinically relevant non-major bleeding occurred in 3.2% of patients
      randomised to warfarin, the incidence of bleeding was significantly higher with
      the edoxaban 60 mg bid (10.6%; p=0.002) and 30 mg bid regimens (7.8%; p=0.029),
      but not with the edoxaban 60 mg qd (3.8%) or 30 mg qd regimens (3.0%). For the
      same total daily dose of 60 mg, both bleeding frequency and trough edoxaban
      concentrations were higher in the 30-mg bid group than in the 60-mg qd group.
      There were no significant differences in hepatic enzyme elevations or bilirubin
      values among the groups. The safety profiles of edoxaban 30 and 60 mg qd in
      patients with AF were similar to warfarin. In contrast, the edoxaban bid regimens
      were associated with more bleeding than warfarin. These results suggest that in
      this three-month study, edoxaban 30 or 60 mg qd are safe and well-tolerated.

PMID- 20694274
TI  - Intriguing outcome of JAK2V617F mutation seen in a patient with MYH9-related
      hereditary macrothrombocytopenia.

PMID- 20694275
TI  - Haemophilia, human immunodeficiency virus and human immunodeficiency virus
      pathogenesis.
AB  - In July 1982, the occurrence of three cases of acquired immunodeficiency syndrome
      (AIDS) in men with haemophilia was an immediate signal to Oscar Ratnoff that AIDS
      was transmissible through blood products. Work that he led provided important and
      clear indication that the AIDS agent was transmissible through pooled plasma
      products and had rapidly infected many men who had haemophilia. Before the blood
      supply was protected, the risk for infection in haemophilia was related directly
      to the intensity of therapy with pooled anti-haemophilic factor concentrates.
      Studies performed among the small proportion of haemophiliacs who remained
      uninfected despite heavy exposure to these plasma products revealed that the rare
      protective genotype - homozygosity for the 32 base pair deletion in the CCR5 gene
      was heavily concentrated in this population. Among those who did not have this
      protective genotype, a state of diminished immune activation distinguished these
      high risk uninfected haemophiliacs from haemophiliacs who later acquired human
      immunodeficiency virus (HIV) infection and from healthy uninfected controls.
      Immune activation state may not only predict risk for HIV acquisition but also
      appears to be an important predictor and likely determinant of HIV disease
      progression. The potential drivers of immune activation in chronic HIV infection
      include HIV itself, other co-infecting pathogens, homeostatic responses to
      cytopenia as well as the recently recognised phenomenon of translocation of
      microbial products across a damaged gut mucosal surface. This latter process is
      particularly compelling as clinical studies have shown a good relationship
      between indices of microbial translocation and markers of both immune activation
      and T cell homeostasis in chronic HIV infection. More recently, we have also
      found evidence that these microbial products also may drive a heightened tendency
      to thrombus formation in HIV infection via induction of monocyte tissue factor
      expression. Thus systemic exposure to microbial elements that are translocated
      through a gut mucosa damaged in the first few weeks of HIV infection may
      contribute to the pathogenesis of both immune deficiency and the heightened risk
      for vascular events that have been noted in persons with HIV infection.

PMID- 20694276
TI  - High platelet turnover and reactivity in renal transplant recipients patients.
AB  - Renal transplant recipients (RTRs) patients are at increased risk of
      cardiovascular morbidity and mortality. We aimed this study to assess reticulated
      platelets (RP), platelet reactivity and von Willebrand factor (vWF) levels in
      RTRs patients. In 150 RTRs patients [84 (56%) not on acetylsalicylic acid (ASA)
      treatment, group A; 66 (44%) on ASA 100 mg treatment, group B] and in 60 healthy
      control subjects, RP were measured by a Sysmex XE-2100 and were expressed as the
      percentage of RP of the total optical platelet count (immature platelet fraction;
      IPF), as the percentage of RP highly fluorescent (H-IPF) and as the absolute
      number of RP (IPF#). Platelet function was assessed by optical aggregometry (PA)
      induced by 1 mmol arachidonic acid (AA-PA), 2 and 10 MUM ADP (ADP2-PA and ADP10
      PA) and 2 MUg/ml collagen (Coll-PA). vWF levels were measured by using a
      miniVidas analyser. Group A and group B showed significant higher values of RP
      than controls. At a multiple linear regression analysis IPF and IPF# were
      significantly and positively related to collagen-PA. By analysing group B
      according to residual platelet reactivity (RPR), we observed a significant higher
      number of RP among patients with RPR by collagen. Moreover at a multiple logistic
      regression analysis, IPF# significantly affected the risk of having a RPR by
      collagen. With regard to vWF, RTRs patients showed higher levels than control
      subjects. We documented a higher platelet turn-over in both groups of RTRs
      patients and increased platelet reactivity in RTRs patients not on ASA therapy
      than controls.

PMID- 20694277
TI  - Enoxaparin for the secondary prevention of placental vascular complications in
      women with abruptio placentae. The pilot randomised controlled NOH-AP trial.
AB  - Administration of heparin in the secondary prevention of placental vascular
      complications is still experimental. In women with a previous placental
      abruption, we investigated the effectiveness of enoxaparin, a low-molecular
      weight heparin, in preventing these complications. Between January 2000 and
      January 2009, 160 women from the NOHA First cohort, with previous abruptio
      placentae but no foetal loss during their first pregnancy and negative for
      antiphospholipid antibodies, were randomised to either a prophylactic daily dose
      of enoxaparin starting from the positive pregnancy test (n=80), or no enoxaparin
      (n=80). The primary outcome was a composite of at least one of the following:
      abruptio placentae, preeclampsia, birthweight < 5th percentile, or foetal loss
      after 20 weeks. Enoxaparin was associated with a lower frequency of primary
      outcome: 12.5% (n=10/80) vs. 31.3 % (25/80), p=0.004, adjusted hazard ratio =
      0.37, 95% confidence interval (0.18-0.77), p=0.011. Enoxaparin was safe, with no
      obvious side-effect, no thrombocytopenia nor major bleeding event excess. This
      pilot study shows that enoxaparin given early during the second pregnancy
      decreases the occurrence of placental vascular complications in women with a
      previous placental abruption during their first pregnancy.

PMID- 20694278
TI  - The role of CD154 in haematopoietic development.
AB  - CD154 (CD40 ligand, CD40L, gp139) is a co-stimulatory molecule of the tumour
      necrosis factor (TNF) family. CD154 was originally discovered on T-cells, and was
      found to be involved in many immune responses including B-cell activation,
      isotype switching, and germinal centre formation. The expression of CD154 on
      other haematopoietic and non-haematopoietic cells suggests that CD154 has other
      functions as well. Indeed, CD154 is involved in many pathological processes,
      including inflammatory and autoimmune diseases. Genetic studies in patients and
      mice taught us that CD154 might affect haematopoietic stem and progenitor cells
      (HSPCs), T-cell, B-cell, and dendritic cell (DC) progenitors. Moreover, the
      development of specific T-cell and DC subsets critically depends on CD154.
      Furthermore, CD154 is involved in lymphoid malignancies. Here we highlight the
      role of CD154 in the developing lymphoid system, including the biology of HSPC
      and lineage-committed T-cell, B-cell, NK, and DC progenitors. Further, the
      clinical and therapeutic implications of CD154 interactions in lymphopoiesis will
      be discussed.

PMID- 20694279
TI  - The D2194G mutation is responsible for increased levels of FV1 in carriers of the
      factor V R2 haplotype.

PMID- 20694280
TI  - The vessel wall: A forgotten player in post thrombotic syndrome.
AB  - Much research in venous thrombotic diseases focuses on the acute thrombotic
      process such as anticoagulation and risk factors. Deep-vein thrombosis directly
      leads to post thrombotic syndrome, and this can cause significant patient
      disability. Little research has focused on the vein wall injury response to the
      thrombotic inflammatory insult. Herein, we review what is currently known about
      this process with emphasis on the matrix, mediators, and vascular medial smooth
      muscle response after thrombotic injury. Translational therapies and potential
      future agents are reviewed.

PMID- 20694282
TI  - New horizons in vascular biology and thrombosis: Highlights from EMVBM 2009.

PMID- 20694281
TI  - Evolution of untreated calf deep-vein thrombosis in high risk symptomatic
      outpatients: the blind, prospective CALTHRO study.
AB  - The natural history of calf deep-vein thrombosis (DVT) is still uncertain and it
      is debated whether it warrants to be diagnosed and treated. We aimed to
      investigate the complication rate of untreated isolated calf DVT (ICDVT).
      Symptomatic outpatients were prospectively managed with serial compression
      ultrasonography (SCUS). Those without proximal DVT and with likely pre-test
      clinical probability (PCP) or altered D-dimer received immediate subsequent
      complete examination of calf deep veins (CCUS) by a different operator. The
      result of CCUS was kept blind both to the managing doctor and the patient and
      disclosed after three months. Primary outcome was the rate of venous
      thromboembolism at three months. We examined 431 subjects (196 males; median age
      68.0 years) in whom five outcomes were recorded (1.2%; 95% confidence intervals
      [CI]: 0.4-2.7). If CCUS results had been available, outcomes would have been
      recorded in 3/424 patients (0.7%; 95% CI: 0.2-2.1) with two events in subjects
      negative at both serial and complete CUS. ICDVT was diagnosed in 65 subjects
      (15.3%; 95% CI: 12-19); of whom 59 remained uneventful (one was lost to follow
      up). A significant higher rate of outcomes was recorded in subjects with than
      without ICDVT (5/64; 7.8%; 95% CI: 3-17 vs. 3/351; 0.8%; 95% CI: 0-2; p=0.003).
      However, after excluding two events picked at serial CUS in subjects with ICDVT,
      the difference became barely significant (3/64; 4.7%; 95% CI: 1-13; p=0.049).
      Thrombotic evolution of untreated ICDVT in high-risk subjects may be relevant.
      Larger studies are needed to address this issue.

PMID- 20694283
TI  - Gamma-glutamyl carboxylase and its influence on warfarin dose.
AB  - Via generation of vitamin K-dependent proteins, gamma-glutamyl carboxylase (GGCX)
      plays a critical role in the vitamin K cycle. Single nucleotide polymorphisms
      (SNPs) in GGCX, therefore, may affect dosing of the vitamin K antagonist,
      warfarin. In a multi-centered, cross-sectional study of 985 patients prescribed
      warfarin therapy, we genotyped for two GGCX SNPs (rs11676382 and rs12714145) and
      quantified their relationship to therapeutic dose. GGCX rs11676382 was a
      significant (p=0.03) predictor of residual dosing error and was associated with a
      6.1% reduction in warfarin dose (95% CI: 0.6%-11.4%) per G allele. The prevalence
      was 14.1% in our predominantly (78%) Caucasian cohort, but the overall
      contribution to dosing accuracy was modest (partial R2 = 0.2%). GGCX rs12714145
      was not a significant predictor of therapeutic dose (p = 0.26). GGCX rs11676382
      is a statistically significant predictor of warfarin dose, but the clinical
      relevance is modest. Given the potentially low marginal cost of adding this SNP
      to existing genotyping platforms, we have modified our non-profit website
      (www.WarfarinDosing.org) to accommodate knowledge of this variant.

PMID- 20694284
TI  - Characterisation and potential diagnostic value of circulating matrix Gla protein
      (MGP) species.
AB  - Matrix gamma-carboxyglutamate (Gla) protein (MGP) is an important local inhibitor
      of vascular calcification, which can undergo two post-translational
      modifications: vitamin K-dependent gamma-glutamate carboxylation and serine
      phosphorylation. While carboxylation is thought to have effects upon binding of
      calcium-ions, phosphorylation is supposed to affect the cellular release of MGP.
      Since both modifications can be exerted incompletely, various MGP species can be
      detected in the circulation. MGP levels were measured with two commercially
      available competitive and two novel sandwich assays in healthy controls, in
      patients with rheumatic disease, aortic valve disease, and end-stage renal
      disease, as well as in volunteers after vitamin K supplementation (VKS) and
      treatment with vitamin K antagonists (VKA). Major differences were found between
      the MGP assays, including significantly different behaviour with regard to
      vascular disease and the response to VKA and VKS. The dual-antibody assay
      measuring non-phosphorylated, non-carboxylated MGP (dp-ucMGP) was particularly
      sensitive for these changes and would be suited to assess the vascular vitamin K
      status. We conclude that the different assays for particular circulating MGP
      species allows the assessment of various aspects of the MGP system.

PMID- 20694285
TI  - Adjunctive treatment with ticagrelor, but not clopidogrel, added to tPA enables
      sustained coronary artery recanalisation with recovery of myocardium perfusion in
      a canine coronary thrombosis model.
AB  - Reperfusion therapy for myocardial infarction is limited by significant re
      occlusion rates and less-than-optimal myocardial tissue perfusion. It was the
      objective of this study to assess and compare the effect of ticagrelor, the first
      reversibly binding oral P2Y12 receptor antagonist, with that of clopidogrel, in
      conjunction with thrombolytic therapy, on platelet aggregation, thrombus
      formation, and myocardial perfusion in a canine model. Thrombus formation was
      induced by electrolytic injury and blood flow was measured with a Doppler
      ultrasonic flowmeter. All animals received tissue plasminogen activator (tPA) (1
      mg/kg over 20 min); 10 animals received clopidogrel (10 mg/kg IV bolus over 5
      min), 10 animals received ticagrelor initiated with a 1-min bolus (75
      microg/kg/min), followed by continuous infusion (10 microg/kg/min) for 2 h, and
      10 animals received IV saline. Re-occlusion rate and cyclic flow variation
      decreased with ticagrelor compared to saline groups (p<0.05). Adenosine phosphate
      (ADP)-induced platelet aggregation decreased with ticagrelor (1.9% +/- 2.67) and
      clopidogrel (1.11% +/- 2.0) vs. saline (26.3% +/- 23.5, p<0.05) at the end of
      adjunctive therapy. Bleeding time increased in the clopidogrel compared to the
      ticagrelor group (p=0.01). Infarct size was reduced with ticagrelor compared to
      the clopidogrel and saline groups (p<0.05). Blood flow remained significantly
      below baseline values at 20 min after tPA administration in the saline and
      clopidogrel groups but not in the ticagrelor group. In conclusion, in a dog
      coronary thrombosis model, ticagrelor blocks ADP-induced platelet activation and
      aggregation; prevents platelet-mediated thrombosis; prolongs reperfusion time and
      reduces re-occlusion and cyclic flow variation; and significantly decreases
      infarct size and rapidly restores myocardial tissue perfusion.

PMID- 20694286
TI  - [SENPE'S working group on bioethics].

PMID- 20694287
TI  - Dietary fiber and its interaction with drugs.
AB  - As the intake of purified dietary fibers is increasing in the society, it is
      necessary to know how these fibers interact with simultaneously administered
      drugs, in order to ensure adequate therapeutic effects, minimizing the risk for
      adverse effects. This paper reviews the literature on the interactions between
      different types of purified fibers and several drugs.

PMID- 20694288
TI  - [Education on nutrition: from the university to specialized care].
AB  - The 7th Abbott-SENPE Forum is structured facing the new regulations of the
      European Space of High Education regarding the studies on Nutrition in the
      different degrees (Medicine, Pharmacology, Nutrition, Nursing) and post-doctoral
      education. A multi-professional and multidisciplinary discussion on the current
      situation of university education on nutrition, and its capabilities and
      limitations, is carried out. The value of the role of continuous medical
      education, the inhouse training programme, masters, and of scientific societies
      is also assessed. It is concluded that there is a need to urge academic
      authorities, the National Commission of Medical Specialties, the persons in
      charge of continuous medical education, and scientific societies of the
      importance of the studies relating to nutrition, feeding, and dietetics at both
      pre-graduate and post-graduate educational levels, and to implement and develop
      these studies in their areas of influence.

PMID- 20694289
TI  - [Glossary of bioethics terms frequently used in nutrition support].
AB  - Bioethical decisions are present in every clinical decision. Nutrition support
      participates the same situation. Feeding critically ill patients, etriminal
      patients or in permanent vegetative status is almost always involved in
      bioethical dilemmas. A common problem is the confusion in concepts regarding
      bioethics. This lack of uniformity does not help in the deliberation process.
      From the Working Group in Bioethics of the Spanish Society for Parenteral and
      Enteral Nutrition Support (SENPE) it has been considered to gather the commonest
      terms used in our academic area. Each term is accompanied by a definition, a
      description or a commentary related to its main application.

PMID- 20694290
TI  - [Effect of an oral hyperproteic nutritional supplement in malnourished elderly
      patients in nursing homes].
AB  - INTRODUCTION: Nutritional problems develop complications in geriatric patients
      and increase their morbidity and mortality. Hyperproteic nutritional supplements
      are one of the options to improve nutritional deficiencies. OBJECTIVES: To assess
      the beneficial effect and tolerance of one hyperproteic nutritional supplement
      (Ensure Plus High Protein, Abbott Laboratories, S.A.) in malnourished subjects
      over 65 years. METHODS: Observational, prospective, open, multicenter study. We
      included malnourished subjects over 65 years living in nursing homes located in
      Spain. Malnutrition was considered as GNRI score < 92 or BMI < 19. Before
      inclusion, we obtained signed informed consent of patients or their relatives.
      All participants received Ensure Plus High Protein for 8 weeks. The primary
      endpoints were changes observed in weight, BMI and GNRI. RESULTS: We analyzed 255
      evaluable patients valid for intention-to-treat (ITT) analysis and 243 for the
      per-protocol (PP) analysis; 69% (n = 172) were female and 31% (n = 77) male. The
      average protein amount administered was 51 g/day. At the end of the study,
      statistically significant differences (p < 0.001) were found in weight, BMI and
      GNRI when compared to baseline, both in the ITT and the PP analysis. The average
      weight increase was (mean +/- SE) 2.86 +/- 0.13 kg for PP analysis; 80% of
      participants (n = 202) achieved a weight gain > 1 kg and 96 patients (39.5% PP
      analysis) had a weight gain > 7%. CONCLUSIONS: The addition of a hyperproteic
      oral nutritional supplement contributes positively in improving the nutritional
      status of our study malnourished geriatric patients in terms of significant
      increase in body weight, BMI and GNRI.

PMID- 20694291
TI  - [Pro-hepcidin, its relation with indicators of iron metabolism and of
      inflammation in patients hemodialyzed treated or not with recombinant
      erythropoietin].
AB  - Hepcidin, an antimicrobial peptide which synthesis is regulated by iron status
      and inflammation, plays an important role in iron homeostasis in hemodialysed
      (HD) patients. It is measured by measuring serum prohepcidin. OBJECTIVE: To
      determine serum prohepcidin levels and their relationship with serum ferritin, C
      reactive protein (CRP), and albumin in HD patients treated or not with
      recombinant erythropoietin (EPO) that attended the Health Centre of the Carabobo
      State in Venezuela. METHODOLOGY: This is a descriptive, correlational, and field
      investigation with a sample comprised by 71 HD patients of whom 57 were treated
      with EPO. Serum prohepcidin, ferritin, haemoglobin, hematocrit, CRP, and albumin
      were determined. Anaemia (haemoglobin < 10 g/dL) and iron deficiency (ferritin <
      100 ng/mL) were defined according to the criteria recommended by the K/DOQUI
      group. Reference values: Albumin 3.5-4.8 g/dL, and for acute inflammatory
      conditions (CRP > 10 mg/L.). RESULTS: The mean value for prohepcidin was 397.5
      ng/mL. A high percentage of anaemia was observed (87.3%) and 22.5% of the
      patients had low levels of serum ferritin. There were no statistically
      significant differences for ferritin, albumin, CRP, or prohepcidin, between
      patients with and without EPO therapy. Only the CRP value was significantly
      correlated (rho = 0.276; p = 0.020) with prohepcidin. CONCLUSION: HD patients
      present high levels of prohepcidin, and this may be due to the common ongoing
      inflammatory process in these patients and not to the iron status measured
      through serum ferritin levels.

PMID- 20694292
TI  - Polyphenolic profile and antiproliferative activity of bioaccessible fractions of
      zinc-fortified fruit beverages in human colon cancer cell lines.
AB  - INTRODUCTION: Colorectal cancer risks could be reduced by polyphenol-rich diets
      that inhibit tumour cell growth. AIMS: To determine the polyphenolic profile of
      four fruit beverages (FbZn, FbZnFe, FbZnM and FbZnFeM) as affected by the
      presence of Zn with/without Fe and with/without skimmed milk, and the digestion
      conditions. To evaluate the antiproliferative activity of bioaccessible fractions
      against Caco-2 and HT-29 cells. To clarify whether cell cycle arrest and/or
      apoptosis is involved in their possible antiproliferative activity. METHODS: The
      polyphenolic profiles were analyzed by RP-HPLC-DAD before and after in vitro
      gastrointestinal digestion. Cell proliferation and viability were measured using
      Trypan blue test, mitochondrial enzyme activity by means MTT test, cell cycle
      distribution using flow cytometry and apoptosis by means Hoechst dye. RESULTS AND
      DISCUSSION: The presence of zinc, iron and/or milk decreased the soluble
      extractable phenolic content before digestion probably by chelate formation, FbZn
      and FbZnFe being the samples with the highest soluble extractable phenolics.
      After digestion, a decrease in phenolics was observed in all zinc-fortified
      samples (up to 32% with respect to the original fruit beverages) - the FbZnFeM
      sample showing the lowest soluble extractable phenolic content, though with the
      lowest percentage decrease in phenolics (14%). FbZnM digest (approximately 50
      microM total soluble extractable phenolics) was the sample that most inhibited
      Caco-2 and HT-29 cell proliferation after 24 h of incubation, without
      cytotoxicity. The specific combination of phytochemicals in FbZnM digest proved
      cytostatic and significantly suppressed proliferation through cell cycle arrest
      in the S-phase in both cell lines, without apoptosis.

PMID- 20694293
TI  - Role of -55CT polymorphism of UCP3 gene on non alcoholic fatty liver disease and
      insulin resistance in patients with obesity.
AB  - BACKGROUND AND AIMS: Some studies have pointed to a role of UCP3 in the
      regulation of biochemical and fat parameters in overweight patients. The aim of
      our study was to investigate the influence of -55CT polymorphism of UCP3 gene
      (rs1800849) on histological changes and insulin resistance in patients with non
      alcoholic fatty liver disease (NAFLD). MATERIAL AND METHODS: A population of 39
      patients with NAFLD was recruited in a cross sectional study. The inclusion
      criterion was the presence of biopsy-proven NAFLD. A biochemical analysis of
      serum (lipid profile, and adipocytokines) was measured. An anthropometric
      analysis was assessed, too. Genotype of UCP3 gene -55CT was studied. RESULTS:
      Nine patients (23%) had the genotype 55CC (mutant type group) and 30 patients
      (77%) 55CT (wild type group).TT genotype was not detected. Insulin levels and
      HOMA were higher in mutant type group (insulin: 17.7 +/- 10.9 mUI/L vs 11.9 +/-
      4.7 mUI/L/; p < 0.05) and (HOMA: 3.2 +/- 1.8 vs 4.5 +/- 2.8; p < 0.05).
      Adiponectin levels were lower in mutants type group (36.5 +/- 28.1 ug/ml vs 21.5
      +/- 18.6 ug/ml:p < 0.05). Moderate-severe inflammation and moderate-severe
      steatosis were more frequent in mutant type group, with higher levels of insulin
      and lower levels of adiponectin than mild stages. CONCLUSION: -55CT genotype is
      associated with high insulin resistance and low adiponectin levels than -55CC
      genotype. Patients with -55CT genotype have more frequently moderate-severe
      steatosis and inflammation than -55CC genotype.

PMID- 20694294
TI  - Evaluation of chemopreventive response of two cycloxygenase-2 inhibitors,
      etoricoxib and diclofenac in rat colon cancer using FTIR and NMR spectroscopic
      techniques.
AB  - Non steroidal anti inflammatory drugs (NSAIDs) are efficacious in chemoprevention
      of colorectal cancer. Therefore, the potential ability of Etoricoxib, a selective
      cycloxygenase-2(COX-2) inhibitor and Diclofenac, a preferential COX-2 inhibitor
      are considered in the chemoprevention of 1, 2-dimethylhydrazine (DMH) induced
      colon carcinogenesis in rat model. DMH was injected s.c. for six weeks while
      Etoricoxib and Diclofenac were fed daily orally alone and also in combination
      with an weekly subcutaneous injection of 1,2-dimethylhydrazine dihydrochloride
      (DMH) to the rats. After the treatment period of 6 weeks the animals were
      sacrificed by an overdose of ether anesthesia and the colonic tissues were
      removed and studied by the FTIR and NMR Spectroscopic techniques to evaluate the
      changes occurring in the lipid bilayer of colonic membrane lipids. The
      alterations in wave number of FTIR spectra as well as the chemical shifts of NMR
      spectra were recorded which signify the modulation of membrane lipids during
      colon carcinogenesis and possible cancer prevention by the oral administration of
      NSAIDs in an experimental model of chemical induced colon carcinogenesis.

PMID- 20694295
TI  - Life quality of postsurgical patients with colorectal cancer after supplemented
      diet with agaricus sylvaticus fungus.
AB  - INTRODUCTION: Therapeutical alternatives, directed to improve life quality and
      reduce adverse effects of cancer treatment, have been the purpose of studies that
      try to prove the immunomodulator efficacy of medicinal fungi as coadjuvant for
      conventional therapies. OBJECTIVE: The objective of this study was to evaluate
      the impact on the life quality of post-surgical patients with colorectal cancer
      after supplemented diet with Agaricus sylvaticus fungus cultivated in Brazil.
      METHODS: Randomized, double-blind, placebo-controlled clinical trial carried out
      at the Federal District Base Hospital-Brazil, for six months. Samples of 56
      enrolled patients (24 men and 32 women), stadium phases I, II and III, separated
      as placebo and Agaricus sylvaticus (30 mg/kg/day) supplemented groups. Form
      standard and direct anamnesis-standard were used to evaluate indicators for life
      quality. The method of analysis was qualitative and descriptive, processed with
      Microsoft Excel 2003 and Epi Info 2004 programs. The protocol was approved by the
      Ethics Research Committee-Health Department-Federal District. RESULTS: After six
      months of treatment, the supplemented group had increased adhesion to physical
      activity; improved disposition and good mood; reduced complaints of pains and
      alterations of sleep such as insomnia and restless sleep; presenting more
      appetite, reduced constipation, diarrhea, alternate diarrhea/constipation,
      flatulence, flatus retention, pyrosis, postprandial fullness, nausea, abdominal
      distention and abdominal pain, facts not observed in the placebo group.
      CONCLUSIONS: The results suggest that a dietary supplement with Agaricus
      sylvaticus fungus is capable of improving the life quality of patients with
      colorectal cancer in post-surgical phase.

PMID- 20694296
TI  - Chronic liver disease and cirrhosis mortality and social deprivation: a spatial
      analysis in small areas of Madrid region.
AB  - OBJECTIVES: To study census-tract distribution of chronic liver disease and
      cirrhosis mortality in the Madrid Region and its association with socio-economic
      deprivation. METHODS: Cross-sectional, ecological (3906 census-tract) study,
      using mortality data for 1996-2003 and a deprivation index drawn up on the basis
      of 2001 census data. Standardised mortality ratios were calculated taking Spanish
      rates for 2001 as reference. Smoothed census-tract relative risks were computed
      using the Besag-York-Mollie model. Relative risks (RRs) of dying and their 95%
      credibility intervals (95% CIs) were calculated according to quartiles of the
      deprivation index (with the fourth quartile -Q- of the indicator being the most
      unfavourable situation). Maps were plotted depicting the distribution of the
      posterior probability of RR > 1. RESULTS: Census tracts with a high risk of
      mortality were detected, mostly located in the centre and on the eastern, south
      eastern and south-western fringes of the city of Madrid. Mortality increased with
      deprivation. RRs of mortality according to quartiles of the deprivation index
      were: Q2 = 1.5 (CI: 1.3-1.6), Q3 = 1.9 (CI:1.7-2.2) and Q4 = 2.5 (CI:2.2-2.8) for
      men; and Q2 = 1.3 (CI:1.1-1.5), Q3 = 1.5 (CI:1.3-1.7) and Q4 = 1.6 (CI:1.3-1.8)
      for women. CONCLUSIONS: This small-area study enabled census tracts with excess
      mortality eligible for a special public health intervention to be identified, and
      their association with socio-economic deprivation to be confirmed.

PMID- 20694297
TI  - [Comparative study of two enteral feeding formulas in hospitalized elders: casein
      versus soybean protein].
AB  - OBJECTIVES: To compare the incidence of gastrointestinal side effects of two
      enteral feeding formulas with changes in the origin of protein (casein and
      isolated soy protein) in hospitalised elderly patients. METHOD: A cross sectional
      survey was done among a sample of elderly patients carrying nasogastric tube
      admitted to the Reina Sofia General Hospital (Murcia) during a period of 6
      months. A formula based on casein or soybean protein was randomly assigned. The
      variables studied were: age, sex, cause for indication of EN, duration of the EN
      and maximum amount of EN administered per day. Nutritional status at admission
      and discharge, mortality and gastrointestinal side effects (diarrhoea,
      constipation, vomits or regurgitation) were also collected. Statistical analyses
      were performed with the Student's T and chi 2 tests, with a significance of 95%.
      RESULTS: Sample conformed by 50 patients over 65 years (48% casein, 52% soybean)
      without statistically significant differences in age nor cause of indication of
      the EN. Either there were no differences in the nutritional status at the
      admission and discharge in both groups. Significant differences were observed in
      the incidence of diarrhoea (C: 45.83%, S: 7.69%, p = 0.009) and vomits (C:
      41.66%, S: 15.38%, p = 0.05). CONCLUSIONS: A significant reduction in the
      incidence of gastrointestinal complications, a reduction in the incidence of
      ulcers by pressure and less mortality occurred on the group that took formula
      based on the soybean protein. The individualized nutritional evaluation must be
      performed routinely when the patient is admitted to the hospital for detection
      and treatment of early signs of malnutrition.

PMID- 20694298
TI  - Food habits and nutritional status of adolescents in Emilia-Romagna, Italy.
AB  - INTRODUCTION: The prevalence of childhood and adolescent obesity is increasing,
      with negative medical and psychosocial consequences. AIMS: This study examines
      the association between weight status and nutrient intake, sport and leisure
      habits of middle school students in Bologna (Italy). METHODS: Anthropometric data
      (height, weight) of 598 subjects (321 males and 277 females) 11-14 years old were
      collected. Questionnaires on nutrient intake, sport and leisure behaviour were
      administered. RESULTS: Protein, carbohydrate and total fat intakes of the
      adolescents were higher than the recommended ranges in all age groups and in both
      sexes. The proportion of energy from protein and total fat was higher than
      recommended, but the percentage from carbohydrate was lower. A significant
      proportion of the adolescents had a cholesterol intake above the Italian RDA and
      lower than recommended intakes for micronutrients. The prevalence of overweight
      and obesity is higher in males than in females at all ages (overweight: 35.2 vs
      31.6 at 11 yrs.; 27.5 vs 20.2 at 12 yrs.; 18.6 vs 17.8 at 13 yrs.; 18.7 vs 10.9
      at 14 yrs.; obesity: 5.5 vs 3.2 at 12 yrs.; 3.9 vs 1.1 at 13 yrs.; 5.3 vs 3.6 at
      14 yrs.), except in subjects 11 years old (obesity: 7.4 vs 10.5). The overweight
      and obese adolescents consumed less carbohydrates and less fibre than their
      normal weight and underweight counterparts. CONCLUSION: The results of the
      present study indicate an unbalanced diet of the Bologna adolescents, which could
      damage their health and quality of life.

PMID- 20694299
TI  - [Influence of fat diet in glicidic metabolism in obese women with Pro12Pro
      genotype in PPARgamma2 gene].
AB  - INTRODUCTION: The peroxisome proliferator-activated receptor gamma 2 (PPARgamma2)
      is an adipogenic transcription factor that influences in insulin resistance (IR)
      in the presence of agonists such as polyunsaturated fatty acids (PUFA).
      OBJECTIVE: Evaluate the influence of dietary fat in glicidic metabolism in
      morbidly obese women with Pro12Pro genotype in the gene PPARgamma2. METHODS: Were
      selected 25 women with genotype Pro12Pro. The fat intake was estimated by food
      records, being used for the division of groups, GA (until 30% of the total energy
      expenditure (TEE)) and GB (greater than 30% of the TEE). Biochemical and
      anthropometric evaluations were conducted in fasting, following the test meal
      high in n-6 PUFA and postprandial biochemical evaluations. IR and insulin
      sensitivity (IS) were assessed by HOMA-IR (Homeostasis Model Assessment) and
      QUICKI (Quantitative Insulin Sensitivity Check Index), respectively. RESULTS AND
      DISCUSSION: GA presented normal HOMAIR and QUICKI. GB presented higher body mass
      index (BMI), HOMA-IR, saturated fatty acids (SFA) and monounsaturated (MUFA)
      intake higher, compared with GA (p < 0.05). In GA, the MUFA intake was negatively
      correlated with HOMA-IR, fasting glucose and insulin, and positively with QUICKI.
      The fat and SFA intake contributed to the increase in body mass and IR. However,
      MUFA intake may have reduced the impact of high fat diet in glicidic metabolism.
      It is suggested that obese women with Pro12Pro genotype in the PPARgamma2 gene
      avoid high fat and SFA diets, prioritizing MUFA for controlling obesity and
      improving the IS.

PMID- 20694300
TI  - Resistin levels and inflammatory markers in patients with morbid obesity.
AB  - BACKGROUND: The aim of the present study was to explore the relationship of
      resistin levels with inflammatory markers and anthropometric parameters in morbid
      obese patients. SUBJECTS: A population of 46 morbid obese was analyzed. A
      complete nutritional and biochemical evaluation was performed. Patients were
      divided in two groups by median resistin value (3.49 ng/ml), group I (low values,
      average value 2.60 +/- 0.5) and group II (high values, average value 5.71 +/-
      2.25). RESULTS: Patients in the group II had higher weight, BMI, fat mass, waist
      circumference, LDL-cholesterol, triglycerides, fibrinogen and C reactive protein
      than patients in group I. In the multivariate analysis with age- and sex-adjusted
      basal resistin concentration as a dependent variable, only fibrinogen and LDL
      cholesterol remained as an independent predictor in the model (F = 8.5; p <
      0.05). Resistin concentration increase 0.01 ng/ml (CI 95%: 0.003-0.017) for each
      mg/dl of fibrinogen increased. Resistin concentration increase 0.03 ng/ml (CI
      95%: 0.003-0.049) for each mg/dl of LDL-cholesterol increased. CONCLUSION:
      Circulating resistin concentrations are associated with different inflammatory
      markers, triglycerides, LDL cholesterol and anthropometric variables in morbid
      obese patients. Further studies are needed to explore these interesting
      relationships.

PMID- 20694301
TI  - Progression to overweight, obesity and associated factors after antiretroviral
      therapy initiation among Brazilian persons with HIV/AIDS.
AB  - OBJECTIVES: To assess body weight changes, progression to overweight/obesity and
      investigate the associated factors among HIV/AIDS patients. METHODS: A
      retrospective study was conducted involving a sample group of 203 adults with
      HIV/AIDS. Medical records were used to gather demographic, clinical and
      anthropometric information. The variables were compared by Chi-square tests,
      Student's t tests and One-way analysis of variance. RESULTS: The majority of the
      individuals studied were men (72.4%) with an average age of 34.68 +/- 8.3 years,
      and time of HIV infection of 4.12 +/- 1.8 years. 63% of the patients gained
      weight. The greatest weight gain was observed among patients with lower CD4 cell
      count on admission (8.45 +/- 6.6 vs. 5.97 +/- 4.97) p = 0.019. 39/203 new cases
      of overweight/obesity were identified, with a progression rate of 19%. Men were
      more likely to progress to overweight (p < 0.001) and women to obesity (p <
      0.001). A direct and significant relationship was observed between the BMI level
      on admission and being overweight/obese at the end of the study for individuals
      admitted with normal weight. CONCLUSIONS: The results of the study show that in
      the course of HIV infection overweight/obesity affected men and women admitted
      with normal weight, although a greater proportion of women progressed to obesity.
      A higher weight gain contributed in a negative manner to the presence of
      dyslipidemias in these patients. These data show the importance of monitoring
      body weight in the course of HIV/AIDS treatment, even in those individuals who
      present normal body weight.

PMID- 20694302
TI  - [Implication of the anxiety and depression in eating disorders of young obese].
AB  - OBJECTIVES: the goals of the present study were: 1) to compare the levels of
      anxiety, depression, and eating disorders in young patients assisted at a
      children's hospital for obesity; 2) to determine whether anxiety and depression
      explain the symptoms of the eating disorders; and 3) to know which of these
      symptoms better discriminate the young people with different degrees of obesity.
      MATERIALS AND METHOD: Descriptive, cross-sectional study with a sample comprised
      by 281 youngsters (56% girls) aged 11-17 years. The BMI percentiles were
      calculated by using the WHO growth tables. Two study groups were created: severe
      obesity and overweight/light-moderate obesity. The following questionnaires were
      used: Eating Disorders Inventory-2 (EDI-2), depression questionnaire (DQ), and
      Status-Trait Anxiety Questionnaire (STAI). RESULTS: The youngsters with obesity
      showed more psychological problems than youngsters with overweight/light-moderate
      obesity, 12% had anxiety, and 11% depression. In both groups, the behaviours
      related with eating disorders were partially explained by the presence of
      symptoms of anxiety and depression. Dissatisfaction with the body and high
      anxiety trait increased the risk for perpetuating the obesity and were the two
      symptoms that better discriminated the patients with or without severe obesity.
      CONCLUSION: Obesity prevention programmes should include body dissatisfaction and
      the anxiety trait into the assessment and management protocols, and prevent
      anxiety getting fixed as a personality trait.

PMID- 20694303
TI  - Equation to estimate body weight in elderly Mexican women using anthropometric
      measurements.
AB  - INTRODUCTION: Body weight is useful for many medical and nutritional procedures.
      When it is difficult or impossible to measure body weight in
      hospitalized/institutionalized elderly, it can be estimated through equations
      based on anthropometry generated in other countries, although their validity in
      other contexts has been poorly studied. OBJECTIVES: To create and validate an
      equation for estimating body weight for both, hospitalized and nursing home
      residents Mexican elderly women (institutionalized) using anthropometric
      measurements. METHODS: A validation study was carried out in elderly women (> or
      = 60 years old), admitted to the Geriatrics Service of the Hospital Civil de
      Guadalajara "Fray Antonio Alcalde" during February-April 19th (n = 43) and April
      20th-June 2005 (n = 29), and elderly women residing in three nursing homes in the
      Metropolitan Area of Guadalajara evaluated during June 2003-June 2004 (n = 23).
      Subjects were weighed using a scale which was adapted to their clinical situation
      and were anthropometrically assessed. In the first sample, we generated a new
      equation using multiple regression analyses. Then, the equation was validated in
      the other two samples. We also estimated weight using Chumlea's equations: in all
      samples, estimated and actual weights were compared between each other through a
      paired t-test. A p < 0.05 was considered as significant. RESULTS: Mean ages in
      each sample were: 84.3 +/- 7.3, 84.4 +/- 9.1, and 84.2 +/- 8.5 years,
      respectively. Mean actual weights were: 48.2 +/- 13.5, 48.1 +/- 10.1, and 55.0 +/
      12.3 kg, respectively. The resulting equation was: estimated weight = (1.599*
      knee height) +(1.135* mid arm circumference) + (0.735*calf circumference) +
      (0.621* tricipital skinfold thickness)-83.123 (R2 = 0.896, p < 0.001). In
      hospitalized women, there were no significant differences between estimated and
      actual weight (sample 1:D-0.02 +/- 4.3 kg, p = 0.976; sample 2: D-0.7 +/- 4.2 kg,
      p = 0.352). In female nursing homes residents (institutionalized women) weight
      was significantly overestimated (1.9 +/- 3.2 kg p < 0.01), but the mean
      difference was smaller than the ones found using Chumlea's equations.
      CONCLUSIONS: The developed equation predicted accurately hospitalized elderly
      women's body weight in our context. In institutionalized elderly women, weight
      was significantly overestimated. It would be useful to derive equations for
      different settings.uals who present normal body weight.

PMID- 20694304
TI  - Accuracy of sagittal abdominal diameter as predictor of abdominal fat among
      Brazilian adults: a comparation with waist circumference.
AB  - AIM: We aim was to compare the sagittal abdominal diameter (SAD) with waist
      circumference (WC) as a predictor of central obesity among adults and to identify
      the sensitivity and specificity of the best cut-off point for SAD. METHODS: A
      cross-sectional study of 266 Brazilians adults (euthrophic and overweight), aged
      31-84 years old, of which 89 men and 177 women, was carried out. Anthropometric
      measurements such as SAD, weight, height, waist and hip circumferences, waist and
      hip ratio, body mass index, body fat percentage were performed. Receiver
      Operating Characteristics (ROC) curve was used to identify the sensitivity and
      specificity of the best cut off point for SAD as a predictor of central obesity.
      Statistical analysis were considered significant with a value of p < 0.05.
      RESULTS: The SAD measurement was positively correlated with WC for both genders,
      although stronger among overweight and obesity women (r = 0.71; p < 0.001 and r =
      0.79; p < 0.001, respectively) than men. ROC curves identified the best cut-off
      points for SAD of 23.1 cm and 20.1 cm for men and women (96% and 85% sensitivity,
      86% and 84% specificity, respectively). CONCLUSION: SAD measurement may be used
      as an anthropometric tool to identify central obesity among women for presenting
      adequate sensitivity and specificity.

PMID- 20694305
TI  - [Circumferences to evaluate changes in body mass and amount of total fat of women
      in second and third trimester of pregnancy].
AB  - OBJECTIVE: To evaluate the maternal nutritional state through simple
      anthropometric indicators as middle-arm circumference (MAC), half thigh (HTC) and
      calf (CC), to value changes in the body mass and quantity of total fat, in women
      on second and third pregnancy trimester. METHODOLOGY: A sample of 76 pregnant
      aged between 18 and 40 years, from suburban communities of the municipalities
      Baruta and The Hatillo, Venezuela were evaluated. Weigh, height, MAC, HTC and CC,
      besides triceps, biceps, subscapular, half thigh and calf skinfolds were measured
      that allowed the construction of indicators of mass and quantity of total body
      fat. RESULTS: The HTC and CC showed differences (p < 0.05) between second and
      third pregnancy trimester. Average values of MAC presented no statistical
      significance among the evaluated trimesters, neither the arm fat area, but the
      thigh fat area and calf what could explain the differences observed in the
      circumferences of these members among the evaluated trimesters. CONCLUSIONS:
      Circumferences of inferior members (half thigh and calf), probably be the
      variables that can be used for evaluate the anthropometric nutritional maternal
      status, allow to predict the possible changes in the fat component, and therefore
      in the body composition of pregnant.

PMID- 20694306
TI  - [Compared nutritional assessment for older adults at family medicine settings].
AB  - INTRODUCTION AND OBJECTIVE: The nutritional state assessment have important
      implications to consider both: prognosis and prevention of diseases related to
      older adults. This study was designed to compare the assessment of the
      nutritional state, in alder adults, via Mini Nutritional Assessment with those
      obtained via evaluation of caloric ingest and anthropometric, biochemical and
      immunological parameters at family medicine centers. POPULATION AND METHODS: The
      nutritional status was assessed in 153 older adults, 93 men and 64 women, whose
      received medical attention at a primary care unit, the age average was 69.66 +/-
      7.94 years old. The nutritional assessment obtained with Mini Nutritional
      assessment was compared to those obtained via biochemical and immunological
      parameters (hemoglobin, serum total proteins, albumin, cholesterol and
      lymphocytes) and anthropometric parameters (size, weight, body mass index).
      RESULTS: Body Mass Index (BMI) was 26.96 +/- 5.1 kg/m(2). Once the adults were
      evaluated with the MNA questionnaire, malnourishment was found in 47 patients
      (29.9%), risk of malnutrition in 86 patients (54.8%), and no risk for
      malnutrition 24 patients (15.3%). The MNA questionnaire was the strongest
      instrument to assess the nutritional status in older adults and to predict the
      risk of malnutrition in such population, (sensibility =96%, specificity= 98%,
      positive predictive value=97% and negative predictive value= 88%). The most
      important relations founded among variables to assess the nutritional status in
      older adults were the following: MNA-BMI (c(2) = 51.314 con gl = 6, p < 0.001);
      MNA-serum total proteins (c(2) = 46.989, gl = 2; p < 0.001); BMI-serum albumin
      (c(2) = 37.508, gl = 3; p < 0.001); MNA-Daily Carbone-hidrate ingestion (c(2) =
      21.50, gl = 4; p < 0.001); MNA-Daily lipids ingestion (c(2) = , gl = 2; p <
      0.001). CONCLUSION: The MNA predicts in opportune form the risk of malnutrition
      and the state of malnutrition the older adults previously to anthropometric,
      biochemical and immunological parameters. We recommend to use it, to do
      nutritional evaluation of older adults one time a year and in those adults in
      whom the risk of malnutrition or malnutrition have been detected, we recommend to
      complete the nutritional evaluation via determination of biochemical,
      immunological and anthropometric parameters mentioned above.

PMID- 20694307
TI  - [Nutritional status in elderly patients with a hip fracture].
AB  - BACKGROUND AND OBJECTIVE: Undernutrition is very common in elderly patients with
      a hip fracture. Malnutrition is associated with increased risk of complications
      after surgery. Few data exist about the presence of nutritional risk in these
      patients. The aim of this study was to evaluate the prevalence of undernutrition
      and the nutritional risk in elderly patients with a hip fracture admitted to a
      hospital. PATIENTS AND METHOD: A cross sectional study assessing the nutritional
      status of 80 patients with hip fracture (mean age 80 years) was carried out.
      Functional capacity, anthropometric measurements, biochemical markers and dietary
      intake were evaluated. The Mini Nutritional Assessment test has been used to
      detect nutritional risk. RESULTS: 8.8% of patients were undernourished. 43.7% at
      risk of malnutrition and 47.5% well-nourished according to MNA test. If only BMI
      was considered the prevalence of malnutrition was 5%. Energy and micronutrient
      intake was low and could contribute to the development of complications after
      surgery. CONCLUSIONS: Our study shows a high prevalence of nutritional risk in
      elderly patients with a hip fracture. The inclusion of MNA in the preoperative
      evaluation could contribute to a better nutritional intervention during their
      stay in the hospital and to provide specific dietary advices to avoid
      malnutrition after surgery.

PMID- 20694308
TI  - [Body composition assessment in patients with chronic renal failure].
AB  - INTRODUCTION: Assessment of body composition is paramount in early assessment of
      nutritional status impairments due to excess or deficit. There are, however, few
      field reliable methods for this objective for patients with chronic renal failure
      (CRF.). OBJECTIVE: To assess the reliability of the estimations of body
      composition by different methods as compared to dual energy X-ray absorptiometry
      (DEXA) as the gold standard method in patients with CRF and on regular chronic
      haemodialysis. PATIENTS AND METHODS: We assessed body composition in 30
      haemodialysis patients (46.9 +/- 15.1 years (18-76); BMI 25.9 +/- 5.7 kg/m(2)
      (18.1-41.5)), observing agreement in the percentage of fat mass (%FM) between the
      sum of the 4 folds (SP; calibrator Lange) and bioimpedantiometry by using
      different equations (BIA; Biodynamics 450) versus DEXA (Lunar DPX-L). RESULTS: (X
      +/- SD) By BMI, 3 subjects had low weight (10%), 14 normal weight (46.7%), 7
      overweight (23.3%), and 6 obesity (20%). The %FM with SP (30.7 +/- 7.1%)
      significantly differed from DEXA (27.3 +/- 10.3%; p < 0.001). With BIA there was
      a significant difference in %FM with the Deurenberg and Formica equations. The
      %FM obtained with the manufacturer's equations (Segal, Lukaski and Kyle) did not
      show a significant difference from DEXA. With Kyle's equation we observed a
      better agreement (difference with DEXA: -0.58 +/- 4.2%). CONCLUSIONS: We found a
      low percentage of patients with low weight as compared to previous studies. The
      skin folds show low reliability to estimate the fat mass. The bioimpedantiometry,
      using Kile's equation may be a good filed method to assess haemodialysis
      patients.

PMID- 20694309
TI  - [Dietary intakes in a group of marihuana smoking patients].
AB  - BACKGROUND: Marihuana use has effects on appetite; studies in the literature on
      this topic area are limited. The aim of our work was to evaluate the dietary
      intake of marihuana smoking patients. PATIENTS AND METHODS: A total of 32 male
      subjects were enrolled (average age 37.25 +/- 8.8 years). In all patients were
      determined weight, height and body mass index and a three days nutritional
      questionnaire. RESULTS: Total calories intakes were higher (3,350.1 +/- 979
      kcal/day). Distribution of calories was 44.3% of carbohydrates, 14% of proteins
      and 41.7% of lipids (50.6% mono-unsaturate fats, 36.3% saturate fats and 13.1%
      poluunsaturated fats). Total protein intake was 109.6 +/- 38.5 g/day and
      corrected by weight was 1.62 +/- 0.73 g/kg. Low intake of vitamin D, E, folic,
      magnesium and iodine were detected. High intake of vitamin A, C, K, thiamine,
      riboflavine, B6, niacin, B12, calcium, iron and zinc were observed. No
      statistical differences in dietary intake or weight were detected between groups
      of marihuana users by median of consumption time of this drug. CONCLUSIONS:
      Marihuana smoking patients realized a hipercloric and hiperproteic diet, with
      high amounts of fats and with an intake of micronutrients above international
      recommendations. This dietary intake has not related with weight.

PMID- 20694310
TI  - [Post graduation programs in Public Health in Brazil: the vital role of
      evaluation].

PMID- 20694311
TI  - [Post-graduation in Public Health from 1997 to 2007: challenges, advances and
      tendencies].
AB  - This article debates the performance of the Collective Health Post-Graduation in
      the last 12 years. It is based on a wide evaluative research performed by a group
      of researches of the area, through a project financed by CNPq, during the years
      of 2008-2009. This proposal is a sequence of another study with the same
      importance that occurred among the years of 1994-1997 taking it in comparison.
      The investigation realized in 2008-2009 analyzed the field construction, the
      demand, and the alumnus, the teaching staff profile, the scientific production
      and the internationalization of the area. There was field work and the
      utilization of secondary sources, mainly from Cadernos CAPES. The study showed a
      field that is in growing organization and powerful on the point of view of the
      demand, the number of masters and PhDs being titled, the content adequacy and the
      teaching staff as well as the scientific production. Among the persistent
      problems are: the high concentration of programs in the southeast region, the
      difference in quality among them, the difficult to absorption of the number of
      titled and the erratic investment in international cooperation. The Collective
      Health Post-Graduation is increasingly more oriented to the improvement of SUS.

PMID- 20694312
TI  - [Janus bifrons and the post graduation].

PMID- 20694313
TI  - [Leaving the resistance and following to new competences].

PMID- 20694315
TI  - [The field of Collective Health in the courses perspective].
AB  - This article discusses the field of Collective Health from the disciplines that
      structure the curriculum of the Collective Health area postgraduate courses in
      2006. From the database of programs, including master's, doctoral and
      professional masters were classified 1,171 subjects, in what we call disciplinary
      fields, linking this to the P. Bourdieu's notion of champ (field). Twenty-eight
      disciplinary fields were described, in three large groups. It was concluded that
      the field of collective health has a wide range of disciplinary fields,
      especially the frequency: Epidemiology (16%), Humanities and Social Sciences in
      Health (7.9%); Curriculum (7.9%); Systems and Health Services (7.4%), Environment
      and Health (7.2%) Health Policies (6.3%).

PMID- 20694316
TI  - [Public Health post-graduation in Brazil: trajectory].
AB  - In this paper we review the issue of post-graduate in Public Health in Brazil.
      The review aims to situate the main specific aspects of building the field of
      postgraduate studies and its institutionalization, preceded by a study of the
      main features of post-graduate courses. The main sources are documents setting
      out the legislation on the graduate and data on their development in the country.
      All studies reviewed show an increase in the number of programs and courses that
      began in the 1970s, diversification of the names and areas of concentration and
      continuity of regional imbalance, since 66% of the programs are in the Southeast
      region.

PMID- 20694317
TI  - [The curricular issue for academic training plan in Public Health: theoretical
      aspects].
AB  - The article analyses the literature on curriculum and its impact on the field of
      public health. This analysis aims to locate the specific lines of theoretical
      developments of the curriculum in order to establish a theoretical framework and
      conceptual study to the curricula of public health in graduate courses. The main
      source of data is bibliographic, national and international. It was concluded
      that the formulation of a 'curriculum as fact' and a 'curriculum as practice' is
      interesting as starting point for analyzing the structure and process of
      formation of the curricula of graduate health courses. Other points concern the
      need to formalize that the curriculum should be based on a framework to define
      the characteristics that distinguish the contents and methodology of the areas,
      classically known as social science, epidemiology and planning. On the other
      hand, establishing a framework that supports inclusion of new areas and which
      parameters are established between the curriculum of undergraduate and
      postgraduate studies in public health.

PMID- 20694318
TI  - [Qualitative dimensions of the scientific, technological and innovation
      production at Public Health].
AB  - This article shows the results of a qualitative evaluation on the expansion of
      the Collective Health area according with the production of the triennial
      Collective Health Congresses Annals which happen between 1997 to 2006, promoted
      by Abrasco - Brazilian Association of Collective Health. The specific objective
      was to estimate the growth of importance of the area in the scientific as well as
      in the social Brazilian scenario in the last decennary through the analysis of
      aspects and substantive dimensions. The methodological strategy of the study was
      to consider the complexity and data profusion referred to the dimensions of this
      multidisciplinary field (more and more interdisciplinary) of knowledge and
      intervention. From this perspective, analysis and interpretations of document
      sources were done, applying theoretical, methodological and analytical
      referential of the social science and X statistics techniques. It could be
      observed that: (1) in the last decade, the Collective Health area expanded into
      its three subareas (Epidemiology, Planning/Management and Health Services and,
      Human Sciences); (2) there is a tendency of more interactivity among the programs
      and with their communities and the institutions; (3) there is a growth in the
      quantity of authors writing about the field and different authors by article; (4)
      it is being elaborated a big internal specialization into the subareas.

PMID- 20694319
TI  - [Themes and approaches of academic production at Social and Human Sciences in
      Health from 1997 to 2007].
AB  - This article is a summary on the intellectual production of Social and Human
      Science in Health concerned to the Public Health area in Brazil. It includes 498
      articles and books reviews, from eight Public Heath journals consulted in the
      electronic database SciELO. A theoretical and methodological analysis was
      performed on the main and secondary's themes, the changes in the previous
      decades, considering also the literature reviews (1997-2007). The themes and its
      perceptual distributions are: health policies and institutions 32.5% ; health and
      illness 18.5%; gender and health 16.5%; violence and health 9.0%; old age and
      aging 4.0%; human resources, health professions and education 7.5%; social
      studies on sciences production and techniques 7.0% as well as health education
      and communication 4.0%. The results show an academic production growth; the use
      of combined theories, approaches and methodologies; the residual
      interdisciplinary between live science and social science and the guarantee of
      the disciplinarian's approaches. A multi-institutional research agenda is
      recommended to refine the investigations on health conditions and social
      transformations; health policies and services; professional training; knowledge
      and technologies.

PMID- 20694320
TI  - [Epidemiology and Public Health: tendencies of the Brazilian epidemiology
      production regarding volume, indexation and investigation areas - 2001 to 2006].
AB  - This article examines and interprets the trends of epidemiological production in
      Brazil in the Public Health context. CAPES indicators from 2001 to 2006 were used
      as database. We analyzed 26 programs and select the 10 major ones to analyze
      their bibliographic production in indexed journals. It was observed that the
      total production of epidemiological articles accounted for 40% of production in
      Public Health and 55% of the production was published in international journals,
      especially Cadernos de Saude Publica, Revista de Saude Publica and Ciencia &
      Saude Coletiva. The most prevalent themes were public health nutrition, maternal
      and infant health and, infectious diseases, particularly AIDS. Environmental e
      worker's heath, oral health, violence and health of the elderly have been
      ratified as objects of study for the discipline, while meta-analysis and
      geoprocessing appear as a useful tool for health services. We conclude that the
      epidemiological production tends to increase in indexed publications, covering
      various topics and a wide spectrum of relevant issues to Brazilian health policy.

PMID- 20694321
TI  - [Scientific production of Brazilian graduate courses in Public Health during 1998
      2006].
AB  - The massive growth of graduate programs in Brazil, observed in the areas of
      Health Sciences and Public Health, makes it necessary to consider the processes
      underlying the diffusion of science. Qualitative analyses on the main themes of
      the field have been conveyed using scientific journals and a directory of
      research groups. The agreement made between ABRASCO and CAPES opened the
      possibility of using a database that, although construed for the evaluation of
      graduate programs, may be useful for different purposes. In this study, the full
      papers registered in three triennials from 1998 to 2006 were analyzed. In order
      to accomplish this it was necessary to standardize the titles of the scientific
      journals and also the titles of full text articles published, in large part
      because the co-authorship of researchers from different programs resulted in
      duplications of entries. Only then was possible to build a database where every
      article is registered no more than once. From this point, the changes throughout
      the three periods were analyzed, as well as the most frequently consulted
      journals, number of authors, language, national and foreign journals, and
      regional and interregional cooperation. The data presented here may be useful for
      the discussions on the scientific production and dissemination of knowledge in
      the area of Public Health.

PMID- 20694322
TI  - [A frame nearly without retouch of the Public Health post-graduation alumni, 1998
      2007].
AB  - We present the results of a data collection that allowed to identify where are
      and what the alumni of the Public Health post-graduation programs think about
      some attributes of their post-graduation, from 1998 to 2007. By means of two
      distinctive and concomitant phases, this subproject was initiated with
      information request along with the programs. The answers allowed the construction
      of a student census that defended thesis or equivalent, in three modalities:
      doctorate, academic and professional master. Besides the data provision that
      allowed us to construct and describe an academic-professional profile of the
      Public Health area alumni, the information allowed electronic contact with most
      of the alumni located. In the second phase, we sent the alumni a form to be
      answered online, with appreciative questions regarding the role of the post
      graduation on their intellectual and professional path, aiming to characterize
      their post-graduation degree. We forwarded some suggestions to future researches,
      as for example the creation of a standardized and digitalized enrollment form
      open to consultation.

PMID- 20694323
TI  - [International cooperation at Public Health: proposals to a debate].
AB  - In the available literature, there is no study devoted to international
      cooperation in public health. This paper aims to partly fill this gap, raising
      and examining the state of art in this area as well as how it interferes in the
      evaluation of post-graduate programs. The study used secondary data available at
      CAPES "Indicators Journals", during the years of 1998 to 2006. It also analyzes
      foreign scholarships and special programs of cooperation of CAPES from 2005 to
      2009 through a quantitative descriptive methodology. It shows that international
      cooperation in the area is relatively developed in a variety of themes and
      diverse partnerships, focusing in the United States. It is observed a positive
      correlation between the number of international cooperation and a high-concept
      program into the evaluation of CAPES, the last triennium of evaluation. The sub
      areas where there is more cooperation are, in order: epidemiology; planning, and
      others. There is a variety of institutions, themes and subareas involved in
      international cooperation that could be a positive indicator in the evaluation,
      but as far as was possible to infer, no significant correlation in this direction
      was found.

PMID- 20694324
TI  - [Evaluation of egressing students of the specialization course on Family Care
      Health in Espirito Santo State, Brazil].
AB  - The purpose of this study was to evaluate the contribution of the specialization
      course on Family Health Care (PG-PSF), in Espirito Santo State, for the
      reorientation of the practices in health. It is a cross-sectional study with a
      population of 47 egressing students of the PG-PSF course in 2007. It was used a
      semi-structured questionnaire for data collection data. The analysis of the
      generated contributions showed some reports regarding the changes in the work
      actions after the acquired knowledge during the course. The majority of the
      students declared that the acquired knowledge have applicability in their daily
      work. They also declared that can plan their actions based in the epidemic
      profile of the area where worked. The relevance of this course was verified for
      the egressing students, with the perspective of a constant adaptation of the
      contents and improvement of the didactic-pedagogic process, through a system of
      continuous education or permanent education, as well as the attendance processes
      and supervision in service.

PMID- 20694325
TI  - [Undergraduate on Public Health: limits and possibilities as a professional
      education strategy].
AB  - This article aims to call into question Public Health as a field for
      professionalization by systematizing theoretical, social and ethical-political
      bases for undergraduate education. We also attempt to record the trajectory in
      formulating undergraduate courses in that field and, more recently, the emergence
      of these projects in Brazilian Universities. In Brazil, the current projects are
      a result of institutional experience gained in Public Health teaching in
      different undergraduate courses in the field of health. Additionally, there is
      also a teaching tradition in non-degree and master's and PhD graduate courses.
      International experiences from similar courses, as well as orientation from
      international agencies represent important information for such initiatives.
      Furthermore, policies targeting social inclusion and the expansion in the number
      of student places in higher education have been propelling the movement. There is
      also the realization that the Brazilian Public Health System demands new actors
      able to provide answers which are both different and complementary to those
      offered by traditional undergraduate courses. While several institutions are in
      the stage of offering this education to society, this article presents a set of
      elements which are derived from reflection in the epistemological, sociological
      and political-sanitary spheres.

PMID- 20694326
TI  - [An analysis of the Ministry of Health of Brazil investments in research and
      development between 2000-2002: a base line towards future valuations beginning
      with the implementation of the National Health Research Priority Agenda].
AB  - The aim of this paper is to examine the Ministry of Health of Brazil investments
      in research and development in health (R&D/H) between the years of 2000-2002,
      trying to contrast them with the items of the National Health Research Priority
      Agenda, in order to attempt a base line that makes capable future evaluations on
      the inductor role. The data was collected by a research carried out with the main
      goal of measure resources invested in R&D/H in the country on the period,
      considering only the Ministry of Health investments. The researches were
      independently categorized by 2 researchers based on 24 subdivisions which compose
      the Agenda. The amount of the resources invested by the Ministry of Health on the
      period was of R$ 199.3 millions. Most of the expense was related to researches in
      transmittable diseases (31.5%), followed by systems and policies in health
      (16.3%) and communication and information in health (8.6%). Conditions that
      represent a substantial disease burden (non transmittable diseases, mental
      health, violence, accidents and traumas, elderly person health) received relative
      small amount of resource. The work establishes a starting point from which
      managers of scientific and technological policy may assess the progressive
      influence of the Agenda and the reduction of the identified imbalances.

PMID- 20694327
TI  - [Characteristics and limits of Professional Master in the Health area: study with
      alumni from Oswaldo Cruz Foundation].
AB  - This paper discuss findings of a follow-up study with alumni of three graduate
      courses known as "professional master" oriented toward institutional innovation
      in management of science and technology, offered by Oswaldo Cruz Foundation to
      its employees. The study analyzed alumni profile and characteristics, identified
      evidence of changes in their original workplace and assessed the relationship
      between the courses proposals, institutional needs and alumni expectations. The
      paper presents limits and possibilities of this new format of graduate courses,
      emphasizing its evaluation as strategic for institutional development. Despite of
      respondents' satisfaction with the courses, this inquiry discloses institutional
      difficulties to incorporate some innovations, including those concerned to its
      institutional management.

PMID- 20694328
TI  - A framework for examining social stress and susceptibility to air pollution in
      respiratory health.
AB  - There is growing interest in disentangling the health effects of spatially
      clustered social and physical environmental exposures and in exploring potential
      synergies among them, with particular attention directed to the combined effects
      of psychosocial stress and air pollution. Both exposures may be elevated in lower
      income urban communities, and it has been hypothesized that stress, which can
      influence immune function and susceptibility, may potentiate the effects of air
      pollution in respiratory disease onset and exacerbation. In this paper, we review
      the existing epidemiologic and toxicologic evidence on synergistic effects of
      stress and pollution, and describe the physiologic effects of stress and key
      issues related to measuring and evaluating stress as it relates to physical
      environmental exposures and susceptibility. Finally, we identify some of the
      major methodologic challenges ahead as we work toward disentangling the health
      effects of clustered social and physical exposures and accurately describing the
      interplay among these exposures. As this research proceeds, we recommend careful
      attention to the relative temporalities of stress and pollution exposures, to
      nonlinearities in their independent and combined effects, to physiologic pathways
      not elucidated by epidemiologic methods, and to the relative spatial
      distributions of social and physical exposures at multiple geographic scales.

PMID- 20694329
TI  - [Traffic injuries among youth in Goiania, Goias State].
AB  - Traffic injuries are currently one of the world's main public health issues in
      both developed and developing countries. This study aimed to describe the
      circumstances involved in the traffic accidents and the profile of the victims
      attended at the Emergency Hospital of Goiania, aged 15 to 24 years and residents
      in Goiania, Goias State, Brazil. It's a prospective cross-sectional study carried
      out from August 2005 to August 2006 by systematic sampling. Data were analyzed by
      descriptive statistics. Most of the 301 victims were male, mean age of 19.94 +/-
      2.73 years, and drivers. Motorcycles (67.33%) and bicycles (16.67%) were
      frequently mode of transport. Accidents usually occurred around 6 pm, on Fridays
      and Sundays. The victims were generally traveling/walking to/from exercise,
      sports, school, recreational or entertainment activities. Suspicion of alcohol
      use was reported by 15.16% of the cases. More motorcyclists believed that there
      was imprudence/ negligence than the cyclists. Security equipment was not used by
      8.58% of motorcyclists, 95.45% of cyclists. Educational measures for
      motorcyclists and law enforcement highlighting the nights and weekends are
      needed.

PMID- 20694330
TI  - [The human right to adequate food: an urban vision].
AB  - The human right to adequate food is comprehended in two dimensions: being free of
      hunger and denutrition and having access to an adequate food. The urban context,
      in which the possession of food is done primarily through merchandising because
      of its strong consuming appealing, became a big challenge to debate this topic in
      poor districts today. Here we combine considerations of a qualitative study
      carried out in Sao Joao de Meriti, Rio de Janeiro State, joining leaders from
      Pastoral da Crianca in focal group sessions. The unemployment, the sub-employment
      and the difficulty in reaching the public health system, the social assistance
      and basic sanitation were presented as the major obstacles to bring into effect
      the human right to food. It was possible to determine that, among the strategies
      to fight the poverty and hunger, a big highlight is the establishment of mutual
      help mechanisms. The social support, generosity and religiousness were presented
      as the most important categories among the thoughts of the leaders. Facing a
      reality in which poverty and hunger appear as something inherent or become a
      mechanism of change during elections, the issue of the clienteles appears as a
      huge concern and challenge for those leaders.

PMID- 20694331
TI  - [The media and the body: what the young people have to say?].
AB  - The aim of this article is to verify the perception of the young about the
      relation between the media, especially the TV and magazine access and the body of
      the adolescent. It is a cross-section study carried out with 121 adolescents of a
      private school in Sao Paulo. A semi-structured individual interview was applied
      and recorded in magnetic ribbon using the methodology of the discourse of the
      collective subject based in the concept of social representation. The data were
      tabulated using three methodological approaches: central idea; key expressions
      and discourse of the collective subjective. The discourses of adolescents were
      evaluated, indicating that 95% of central ideas expressed relations among TV,
      magazines and the body and the most common ideas were about the stimulation of
      the thinness ideal physicist and the negative influence with hazard experience
      and illnesses appear. In 5% of central ideas registered no relation among TV,
      magazines and the body. We could conclude that young people show the knowledge
      about the intense media's interference in the adolescent body.

PMID- 20694332
TI  - The influence of religiosity on health.
AB  - The relationship between religion and health has been a subject of interest in
      the past and in the latest years becoming increasingly visible in the social,
      behavioral, and health sciences. Among several approaches to be considered, the
      present work provides a briefly discuss concerning the bond between health and
      religiosity in the cure process and diseases treatment. Several investigations
      show that religious participation is related with better outcomes for persons who
      are recovering from physical and mental illness, also the psychology science have
      committed special issues to positive correlations between religious belief and
      practice, mental and physical health and longevity. On the other hand, religion
      may also be associated with negative outcomes and the inappropriate use of health
      services as fanaticism, asceticism, mortifications and oppressive traditionalism.
      The potential for both positive and negative effects of spirituality on health,
      combined with the high levels of engagement with spirituality suggests that this
      area is ripe for future sustained research. Independent of the possible
      mechanisms, if individuals receive health profits by the religion; those should
      be motivated, respecting the individual faith of each one.

PMID- 20694333
TI  - [Social participation in mental health: space of construction of citizenship,
      policy formulation and decision making].
AB  - The article approaches the comprehension of professionals that act in the mental
      health area about the movement of construction of social participation in the
      health system of Fortaleza, Ceara State. The methodology adopted is based upon
      qualitative approach. The study was developed with semi-structured interviews
      with 17 mental health professionals of the city above mentioned. The empirical
      data was analyzed through the technique of thematic content analysis, where it
      was identified three cores of analysis: social participation as space of
      citizenship and policy formulation; oriented to attention of collective needs;
      and decision taking. The study reveals that social participation represents a
      possibility of amplifying X the relations between the Civil Society and the
      State, which makes possible the social intervention in proposals of the health
      policies. It is highlighted the right to health linked to the consolidation of
      democracy in the attention to the needs and collective edification.

PMID- 20694334
TI  - [Participation and creativity as tools of analysis of public policies].
AB  - In the context of current globalization, important modifications of the
      international relations and of the ideological, technical, and cultural
      components in the administration of the States are expressed by non-legitimate
      public action principles which account for social iniquity and the weakening of
      the role of the State. Regardless of its political origin or ideological
      orientation, the economic development plans and programs exhibit a prevailing
      uniformity. The challenge today implies mobilizing in local capacities with the
      objective of changing the quality of public action through the adoption of new
      development strategies able to integrate new social dimensions with other
      mechanisms of action. One of them, the intersectoral action, demands the
      structural revision of the administrative and cultural frontiers of the public
      and private social agents as a means of making a new tentative sociopolitical
      arrangement. The complexity of politics, projects and programs is taken as a
      methodological landmark based on the following theoretical presuppositions:
      integrality, social networks, and sociopraxis, constructing a participative
      process of knowledge to a political analysis in search of a change in the
      approach of the sociopolitical processes, starting from local social networks.

PMID- 20694335
TI  - [Understanding the user's health behavior change through their participation in
      the Family Health Program].
AB  - This study aimed to understand how users from Family Health Program (FHP) make
      their decision about health-illness. It was used the Stages of Change Model from
      Prochaska and DiClemente to identify the level of change of FHP users. It was a
      qualitative research developed with users and FHP health professionals from
      Crato, Ceara State, Brazil. The data were collected by semi-structured
      interviews, focal group and observation from May to September in 2005. They were
      organized by means of content analysis and analyzed in the light of theoretical
      reference. The changes of the FHP users are depicted as following: in the pre
      contemplation stage the emphasis is on disease and care itself. In the
      contemplation stage, the care is on the family. It is centred in the cure and
      treatment of diseases. In the determination stage, we have some improvement
      concerning prevention in the family, with registers of looking around. In the
      action stage, behaviour from the user to reach autonomy and emancipation is
      registered. These results seem to indicate ascendency in FHP users' learning and
      participation towards health promotion.

PMID- 20694336
TI  - [Family Health Strategy: evaluating the access to SUS from the perception of the
      users of the health unit Resistencia, in the region of Sao Pedro, Vitoria,
      Espirito Santo State].
AB  - Family Health is a re-orientation strategy of the assistance model. One of its
      guiding principles is the establishment of a link between the health teams and
      the SUS users. The purpose of this research is to evaluate user access to the
      Family Health Unit (FHU) and the local problems faced. It is an exploratory,
      qualitative research, developed at the FHU Resistencia of Sao Pedro, located in
      the Greater Vitoria, Espirito Santo State, with data collected individually
      through a semi-structured survey. It was found that the main needs of the
      population are incorporated in the services provided by the FHU, and the users
      face many difficulties with access. The main criticism is related to access to
      the specialized services. The majority of the participants of the survey showed
      satisfaction with the access to the services, and were not intimidated to express
      the difficulties faced. The work developed by the Family Heath Strategy (FHS) at
      FHU Resistencia has been contributing to the improvement of the quality of the
      services offered by FHS to the users served, although many problems have been
      identified, which demonstrates the great challenge in redefining the assistance
      model, as proposed by this public policy.

PMID- 20694337
TI  - [Interface between the work of the community health agent and physiotherapist in
      the basic health care].
AB  - The study is intended to identify the actions of the physiotherapist and
      community health agent in the context of the integration of their performances in
      the basic health care. A systematic review was performed with the purpose of
      knowing what are these performances, and then list them. The interest came from
      the "Supervised Training in the Primary Health Care" and the observation of their
      acts. From a law review and updated scientific works related to this subject, we
      noted that both, community health agent and physiotherapist, are important
      professionals in the composition of a health team, once they contribute to the
      qualification of the health actions among the community and the effectiveness of
      an universal, integral and equitable health system. Lastly we found that there is
      an interaction between these professionals and integration among their
      activities.

PMID- 20694338
TI  - [The impact on life quality due to oral conditions in people fifty years or
      above].
AB  - The objective of this work was to evaluate the influence of socio-demographic
      variables and oral health conditions in the quality of life of non
      institutionalized people aged 50 or above, living in Bauru, Sao Paulo State.
      Clinical oral examinations were conducted on a sample of 224 people including
      dental caries, periodontal disease and usage or need of dental prosthesis
      according to WHO suggestions for community dental health surveys. They were also
      asked to answer a questionnaire comprised of 49 questions about the impact of
      their oral status on the activities of daily living (OHIP). Descriptive
      statistics and multiple regression analysis were computed with individual scores
      of each domain as dependent variables. The results were: 60% were retired people,
      42% exercise no social activity and 65.5% earned less than three minimum wages.
      Dentate people had a mean of 15.3 missing teeth, 117 people (53% of the sample)
      had full dentures. It could be concluded that regression analysis showed no socio
      demographic variable but age having a significant impact on quality of life; as
      people get older oral disorders seems to produce lower impact on quality of life.
      As it concerns to oral clinical data only periodontal disease showed impact on
      quality of life.

PMID- 20694339
TI  - [Inequalities in distribution of dental caries in teenagers of Indaiatuba, Sao
      Paulo State, 2004].
AB  - The objectives of this work was to know the dental caries prevalence and
      treatment need, besides the distribution of the dental caries in a population of
      12 year-old teenagers with high incidence of dental caries. 309 adolescents of
      public schools of Indaiatuba, Sao Paulo State, in 2004, were examined. They were
      selected by process systematic random and the exams followed the World Health
      Organization criteria. The percentile of school caries free was of 38.8%. Among
      the adolescents examined, 36.6% (n=113) presented dental caries. DMFT was of 2.50
      (IC95%=2.07-2.93). The decayed component was the highest (61.0%). The coefficient
      of Gini was 0.602 and SiC value was of 5.97 (IC95%=5.32-6.62); in this group
      especially, 74.7% (n=74) presented dental caries activity in the moment of the
      exam. Thus, it can be concluded that the adolescents of this city presented low
      dental caries experience; however, their needs were not assisted, once most of
      DMFT was formed of the decayed component at 12 years old. In the group SiC, it
      was verified that this came quite high, being recommended actions addressed to
      this specific group of adolescents.

PMID- 20694340
TI  - [Reproducibility of a scale for oral health among children and adolescents
      HIV+/AIDS].
AB  - The aim of this study was to investigate the intraobserver reproducibility of a
      Portuguese version scale used to evaluate aspects of oral health among children
      and adolescents HIV+. The scale was proposed by Balbo and a questionnaire was
      applied in two occasions, within a one week period, to 27 children and
      adolescents. The reproducibility was estimated by kappa statistics by point (k).
      With relation to the mother, it was reached a maximum of agreement for items
      related to the importance of maintaining the oral health, diary tooth brushing
      and the individual utilization of dental brush; breath and esthetics presented a
      good agreement. Regarding the children, a regular agreement was observed on the
      dental floss use. In contrast, the respondents had difficulties in reporting the
      name and address of the professionals that gave guidance in prevention activities
      to them. The k-values for perception, care and promotion were 0.48, 0.21 and 0.64
      respectively, pointing to reproducibility levels classified as regular, fair and
      good. Given the different levels of reproducibility offered by the dental scale
      for HIV+ oral health, we suggest that it could be modified, especially in the
      domain of care.

PMID- 20694341
TI  - [Analysis of oral health attention in the Family Health Strategy of the Sanitary
      District VI, Recife, Pernambuco State].
AB  - The aim of this study was to analyze the work process developed by the oral
      health teams of the VI Sanitary District of Recife, Pernambuco State, in 2006. It
      is a descriptive study of qualitative approach in that secondary data were
      obtained of a previous research accomplished in Recife, where the Sanitary
      District VI is located. Four semi-structured interviews were accomplished with
      the oral health coordinator, two surgeon-dentists and a nurse that acted in the
      Family Health Strategy. The results showed that some practices accomplished by
      the teams are still incipient such as the epidemic survey, patient reference and
      counter reference, and the control and evaluation of the actions. However, the
      progress in the preventive vision and in education practice in the professional
      health became evidenced through the interviews. In conclusion, in spite of the
      difficulties for the execution of the practices established by the National
      Policies of Oral Health, it is noticed a change in the attention model in oral
      health, being necessary some adjustments and corrections in the activity of the
      teams, besides a larger participation of other administration levels for the full
      exercise of oral health in the Family Health Strategy.

PMID- 20694342
TI  - [The integrality of the attention in diabetics with periodontal disease].
AB  - The aim of this study was to evaluate the periodontal conditions of individuals
      with diabetes and to analyze how SUS has contributed to the health attention of
      these people in Belo Horizonte, Minas Gerais State. For that, a sample of 300
      individuals was selected and interviews with diabetics and health unit managers
      were conducted. From those, 55% presented gingivitis, 35.3% periodontitis and
      9.7% were healthy. As for the integral attention for diabetics in SUS, it was
      observed that despite the fact that most of them were under medical supervision,
      only 27.3% were under dental treatment in basic health care units, 3.6% had
      specialized dental care and only 3.4% were seen by other health workers.
      Interdisciplinary care and attention in all levels of the system are essential
      factors for the integrality of health actions.

PMID- 20694343
TI  - [Oral health status of elderly women from the Brazilian Federal District].
AB  - Data from Brazilian researches that evaluated oral health of elderly people show
      a worrisome situation. The purpose of this study was to estimate the frequency of
      edentulism, analyze both the use and need profiles of prosthesis, calculate the
      DMFT index and check the condition of periodontal elderly residents in the
      Federal District. One hundred and forty women aged 60 years or above were
      examined. The condition of each prosthesis was evaluated to detect the presence
      of functional or aesthetic damage. Then, clinical examination was carried out to
      detect the number of decayed, missing or filled teeth in order to calculate the
      DMFT index. The periodontal examination included the index of visible plaque,
      bleeding index, measurement of clinical probing depth, measurement of clinical
      attachment level and teeth mobility. The results showed poor oral conditions of
      the patients. The rate of edentulism was high, the DMFT index was elevated (29.8)
      with a predominance of the extracted component (87.1%) and periodontal condition
      was considered severe. From these data we can conclude that the oral condition of
      elderly represented in this study is precarious and reflects the need for health
      promotion and rehabilitation programs for this segment of the population.

PMID- 20694344
TI  - [Health surveillance: foundations, interfaces and tendencies].
AB  - The present article rescues initially the forms, content and operational
      projection of the epidemiological surveillance as indispensable tool for the
      knowledge field and public health practices. After that, we verify that the
      health surveillance model establishes an enlargement of this operational concept
      of surveillance by integrating the collectives and individuals practices in
      different health necessities dimensions, which includes beyond of the risks and
      damages control also the eco-socials determinants. In the sequence, we search to
      dimension the distinct levels of actuation of this sanitary practice articulated
      to the interventions of promotion, protection and recovery under a located and
      integrated logic of the unique system of Brazilian health. Finally, we argue that
      all the conceptual-operational model framework of public health surveillance
      itself constitutes as a politics and sanitary base for the consolidation of the
      health promotion paradigm in the collective health field.

PMID- 20694345
TI  - [From garbage production to residue transformation].
AB  - This research has a starting point the promising articulation between recyclable
      waste materials pickers and visual artists. Their intersection point is the way
      they reshape the remnants of the consumption society: waste pickers give new uses
      to objects bringing dignity to cast out materials, while visual artists reshape
      these subjectively refused objects into art, giving them new social value. This
      study tries to locate the continuity gap we created in regard to waste materials
      processing - what may they tell about us? Where do they stand at our social scale
      of values? Thus it becomes clear how waste objects aren't just technical
      realities but renewed values. Approaching waste objects with a logic that merely
      envisages their technical side would leave behind something they had as an
      essential part.

PMID- 20694346
TI  - [The protocols and the medical decision: evidences based in experience or
      existence?].
AB  - The main purpose of this study is to understand the concepts and interests
      concerning the transformation of the practical quotidian knowledge produced by
      experience into probabilistic epistemological models. The object is the
      argumentation and practices surrounding consensus-forming which knowledge
      criteria are valid for diagnostic and therapeutic decisions. Our starting point
      is Ludwik Fleck's work, which states that facts are not objectively given but
      collectively and contingently created so as to adjust themselves to a style of
      thought. Our research strategy was an ethnographic observation of medical rounds
      and clinical meetings in a cardiology ICU in Rio de Janeiro. The analysis was
      based on the works of Knorr-Cetina (transepistemic arenas) and Perelman's
      argumentation theory. It revealed the consolidation of a tendency to incorporate
      explicit cost-benefit criteria and the interests of different agents such as
      doctors, government and the medical-industrial complex in the introduction of
      protocols. The observation demonstrated an ambivalent use: protocols/scientific
      studies and clinical experience as well. A certain skepticism of the clinicians
      and their relative inability in the usage of the analytic tools of the
      epidemiological thought style were particularly remarkable.

PMID- 20694348
TI  - The persistence of acute respiratory infections as a Public Health problem.

PMID- 20694349
TI  - [International cooperation and affirmative action policies: the role of the Pan
      American Health Organization (PAHO)].
AB  - The article analyzes the formulation, legitimation, and implementation of a
      policy with an ethnic/race approach by the Pan American Health Organization
      (PAHO). The study includes the emergence of the theme within this international
      organization, the institutional dynamics related to it, and the proposals focused
      on the Black population in Latin America. These issues are discussed on the basis
      of interaction between PAHO and a range of intergovernmental agencies and private
      organizations working in the international health domain. Participation by PAHO
      in the ethnic/racial theme provides elements for understanding the dual role
      played by intergovernmental organizations in the new global scenario, as both
      social actors and arenas. As an important social actor in the international
      health field, PAHO has produced and disseminated values and guidelines related to
      the ethnic/racial theme. As an arena, the organization has proven open to various
      interests, seeking to work harmoniously with them through its internal
      administration.

PMID- 20694350
TI  - [Debate on the paper by Maio et al].

PMID- 20694351
TI  - [How to set agendas in International Health?].

PMID- 20694352
TI  - [The incorporation of agenda by international health organizations].

PMID- 20694353
TI  - [From fight to "harmonization"].

PMID- 20694354
TI  - [The authors reply.].

PMID- 20694355
TI  - Suicide time trends in Brazil from 1980 to 2005.
AB  - The aim of this study was to describe suicide time trends in Brazil from 1980 to
      2005. The data were obtained from the National Mortality Information System and
      the Brazilian Institute of Geography and Statistics (IBGE). Suicides rates were
      calculated for the entire period for the country as a whole and the 26 States and
      Federal District. Annual increases or decreases in mortality rates were also
      estimated using Prais-Winsten generalized linear regression. The mean suicide
      rate was 4.12 per 100,000 inhabitants (6.45/100,000 in men and 1.80/100,000 in
      women). The study showed an increasing suicide trend in men (+1.41% per year,
      95%CI: 1.00;1.23) and a decreasing trend in women (-0.53% per year, 95%CI: -0.04;
      1.02). Suicide rates increased with age. In general, for all age groups and for
      both genders, the highest rates were in Sao Paulo and in the States of the South
      and Central-West regions.

PMID- 20694356
TI  - [Temporal evolution of overweight and obesity among Brazilian male adolescents,
      1980-2005].
AB  - Analysis of the temporal trend in obesity shows the increasing risk posed by this
      condition worldwide. This article aims to verify and compare the prevalence rates
      for overweight and obesity in male adolescents in all States of Brazil, from 1980
      to 2005. We used the Brazilian Army's database, with 8,989,508 males 17-19 years
      of age. We defined overweight as body mass index (BMI) from 25 kg/m2 to 29.9
      kg/m2 and obesity as BMI>or=30 kg/m2. The analysis showed an increasing trend in
      the prevalence of overweight and obesity in all States of Brazil for the period
      studied. There was a three-fold increase in adolescents with overweight and a six
      fold increase in obesity. The absolute numbers for overweight were higher than
      for obesity, but the rate of increase over the period was greater for obesity.
      Analyzing the trend in prevalence rates by five-year period, we observed that
      from 1980 to 2005, as the prevalence of overweight decreased, that of obesity
      increased in all States of Brazil.

PMID- 20694357
TI  - Challenges in organizing care networks for the elderly in two regions of Brazil.
AB  - The global trend of ageing populations is present in Brazil. Brazilian society is
      going through an intensive process of transformation, where young adults are
      increasingly fewer, thus raising the question of who will take care of the
      elderly in the 21st Century? There is an urgent need to establish care networks
      for the elderly, covering primary care, including care with housing (Healthy
      Housing), as well as to ensure access to secondary and tertiary levels of care,
      providing early diagnoses and rapid access to treatment. This article reports two
      Brazilian experiences: the restructuring of a shelter for elderly indigents, with
      500 elderly residents in Rio de Janeiro, which involved a broad process of
      humanization, with strong physical restructuring of the buildings that dated from
      1930; and the process of organizing the care referral line for the elderly within
      the Conceicao Hospital Group, in Rio Grande do Sul State, which included a health
      care complex with diverse health units, encompassing all stages of care: from
      primary care to the most complex hospital treatment.

PMID- 20694358
TI  - [Characteristics, depressive symptoms, and associated factors in incarcerated
      women in the State of Rio Grande do Sul, Brazil].
AB  - The study's objective was to describe the socio-demographic and clinical
      characteristics of women inmates and verify the prevalence of depressive symptoms
      and hopelessness and drug and alcohol use, abuse, and addiction. The sample
      included 287 inmates at a Women's Penitentiary in the State of Rio Grande do Sul,
      Brasil. The study design was quantitative and cross-sectional. According to the
      findings, the typical female inmate was single, young, had at least two children,
      had worked in the informal market, and had low social and/or economic status and
      incomplete primary schooling. There was a high prevalence of depressive symptoms
      and drug use, abuse, and addiction, but a low prevalence of symptoms of
      hopelessness. Various factors, especially linked to the participants' life
      history, were significantly associated with depressive symptoms.

PMID- 20694359
TI  - [Diarrheal illnesses on the Ecuadorian coast: socio-environmental changes and
      health concepts].
AB  - The authors present an ethnoepidemiological study of diarrheal illnesses in 21
      communities on the northern coast of Ecuador, where numerous social and
      environmental changes have taken place since 2001 due to a new highway. As
      communities realize that nature itself is changing, changes occur in their
      interpretations of health and disease, which the authors present through a
      taxonomic classification of diarrheal illnesses. Given the high incidence of
      diarrheal diseases, alternative concepts have emerged (as compared to those of
      biomedicine) in relation to causes, symptoms, and treatments. The non-biomedical
      and biomedical systems overlap, with mixtures of coexistence and resistance.
      Recognizing this reality means understanding a series of challenges for the
      official health system, including the indiscriminate use of antibiotics, non-use
      of health services for some diseases, and perceived relations between
      environmental contamination and the efficacy of modern and traditional medicines.

PMID- 20694360
TI  - [Cross-cultural adaptation of section A of the Cambridge Examination for Mental
      Disorders of the Elderly-Revised Version (CAMDEX-R) for dementia diagnosis].
AB  - This article concerns the first phase of the cross-cultural equivalence of
      Section A in the Cambridge Examination for Mental Disorders of the Elderly
      Revised Version (CAMDEX-R), a clinical interview for dementia diagnosis.
      Evaluating conceptual and item equivalencies involved a literature review and
      expert groups. Semantic equivalence involved translations of the original into
      Portuguese and back-translations, with analysis of the versions and the original
      text; meetings with experts; discussions with 52 elders using the focus group
      technique; further meeting with experts; pretesting on 35 elders; and elaboration
      of the final version. For the reliability analysis, the version was applied to
      160 patients. Inter-observer reliability was nearly perfect in all sub-sections
      of present state and in individual items of past medical history. Test-retest
      reliability was moderate or higher in the sub-sections and substantial or nearly
      perfect in 70% of the items in past history. The Brazilian version shows
      satisfactory equivalence to the original and good reliability levels.

PMID- 20694361
TI  - Qualitative analysis of the diet of a probabilistic sample of schoolchildren from
      Florianopolis, Santa Catarina State, Brazil, using the Previous Day Food
      Questionnaire.
AB  - A qualitative evaluation of the diet of a probabilistic sample of 7-10 year old
      schoolchildren (n=1,232) from Florianopolis (southern Brazil) was carried out by
      analyzing compliance with recommendations from the Brazilian Food Guidelines. The
      strengths and limitations of the Previous Day Food Questionnaire (PDFQ) are also
      presented. Frequencies of intake were defined as how many times per day the food
      group was reported on the PDFQ. The percentages of schoolchildren who met the
      minimum recommendations and who ate foods that were not recommended in the
      guidelines were compared for boys versus girls, private versus public school and
      by family income level. Although most of the children complied with the
      guidelines regarding consumption of meat/fish, dry beans, sweets, and eating
      three meals and two snacks, only 6.5% of the children met the recommendations for
      cereals, and 15% for fruit and vegetables. The PDFQ was confirmed as a practical
      and cost-effective method for the evaluation of compliance with health promotion
      targets.

PMID- 20694362
TI  - [Profile of suicide attempts using intentional overdose with medicines, treated
      by a poison control center in Parana State, Brazil].
AB  - This study presents the profile of suicide attempts using intentional overdose
      with medicines, treated at the Poison Control Center in Londrina, Parana State,
      Brazil. A retrospective study of cases treated from 1997 to 2007 was performed.
      Suicide attempts were significant among unemployed men, housewives, and retired
      women, and there was an association with other substances in 51.5% of the cases,
      with a higher frequency among men. 51.1% of the men combined the medicine with an
      alcoholic beverage, while in women, 84.8% of the associations involved other
      medicines. The most frequent pharmacological groups were tranquilizers (25.5%),
      antidepressants (17%), anticonvulsants (15%), and NSAIDs (11.9%). Prescribers
      must evaluate patients correctly before prescribing psychoactive drugs, since
      this is the pharmacological group most frequently associated with suicide
      attempts. Awareness-raising campaigns for rational use of medicines and social
      programs for suicidal patients should also help decrease the frequency of such
      cases.

PMID- 20694363
TI  - [Volunteers and negotiation of anti-HIV vaccine protocols in Brazil].
AB  - This study monitored the protocol of a clinical trial for experimental anti-HIV
      vaccines in Rio de Janeiro, Brazil, focusing on the recruitment, selection, and
      follow-up of volunteers. The techniques included observation of the research
      center's routine and interviews with health professionals and volunteers. The
      results show that the trial is a collective activity, in which constant
      negotiations are needed between the protocol requirements and what can, should,
      or must be adapted in order for it to work, as a function of: prolonged time
      before the trial's approval by the regulatory bodies, difficulties in recruiting
      volunteers, and even larger problems like discontinuity in the vaccines (which
      occurred in a specific protocol). The article discusses how the protocol's
      application extends beyond the technical and scientific "script", transforming it
      into a boundary object between different social worlds. The protocol is adapted
      according to a local order, based on the dynamics of social relations and the
      constant interrelationship between science, society, technique, and politics.

PMID- 20694364
TI  - [Use of the Internet to report congenital malformations on birth certificates at
      four public maternity hospitals in the city of Sao Paulo, Brazil].
AB  - The aim of this study was to improve the completion of item 34 on birth
      certificates at four maternity hospitals in the city of Sao Paulo, Brazil, in the
      year 2008. The database of the Municipal Health Department's Information System
      on Live Births was used to monitor trends in reporting birth defects. An
      electronic web-based medical record was used to refer indeterminate cases to a
      leading medical genetics referral center. The electronic medical record contained
      the patient history, physical examination, and photographs of the newborn. Four
      maternity hospitals were assessed, with a total of 10,000 births during the year.
      None of the four hospitals had a staff geneticist. According to the Information
      System on Live Births, there was an increase in the number of birth defects
      reported by the four maternity hospitals when compared to previous years and to
      records for the city of Sao Paulo as a whole. Based on the findings, the web
      based referral and counter-referral method proved efficient.

PMID- 20694365
TI  - [Prevalence of intestinal constipation and associated factors: a population-based
      study in Pelotas, Rio Grande do Sul State, Brazil, 2007].
AB  - The aim of this study was to estimate the prevalence of intestinal constipation
      and associated factors in adults 20 years and older. A cross-sectional study was
      conducted in the rural area of Pelotas, Rio Grande do Sul State, Brazil, in 2007.
      Intestinal constipation was defined according to the Rome III criteria. The study
      began with a descriptive analysis, followed by bivariate and multivariate
      analyses using Poisson regression. Prevalence of intestinal constipation was
      26.9% (95%CI: 25.1-28.8). Women had 2.5 times more constipation than men (36.8%
      vs. 13.9%). The adjusted analysis showed that risk factors for men were age (>60
      years), skin color (black/brown), and low economic status. Among women, age was
      inversely related, i.e., having a protective effect among the elderly. Intestinal
      constipation is common in this population. Associated factors were the same for
      men and women, except socioeconomic status, which showed no association in women.

PMID- 20694366
TI  - [Hospitalization and risk factors among elderly individuals living in nursing
      homes].
AB  - The aim of the present study was to evaluate the prevalence of hospital
      admissions over a one-year period and associated factors through a survey of
      elderly subjects living in nursing homes in Pelotas, Rio Grande do Sul State,
      Brazil. Hospital admissions were assessed using the question: "From 'month' last
      year to today, were you admitted to a hospital?" Out of 521 eligible individuals,
      information was collected for 466 (89.4%). Prevalence of hospital admissions in
      the previous 12 months was 23.9% (95%CI: 19.9-27.8). Admissions were directly
      associated with: inability to perform basic activities of daily living, falls,
      and history of smoking. Single and divorced individuals were less likely to be
      hospitalized. There was an inverse association between hospitalization and self
      rated health. The high prevalence of hospitalization among elderly subjects
      living in nursing homes is an important indicator for the organization of health
      services, in order to ensure high-quality services for a population group
      experiencing a demographic and epidemiological transition.

PMID- 20694367
TI  - [Incidence of respiratory symptoms and the association with air pollution in
      preschoolers: a multilevel analysis].
AB  - The aim of this study was to evaluate the association between air pollution and
      respiratory symptoms in preschoolers from Bucaramanga, Colombia. A cohort study
      was conducted by reporting daily symptoms in preschoolers living in two zones of
      the city with different PM10 air pollution levels. Individual and neighborhood
      variables were included in a multilevel analysis. In 707 preschoolers followed
      for a year, sneezing and cough with mucus were the most frequent symptoms, with
      incidence rates of 277.2 and 203.3 events per 100 child months at risk. In the
      high pollution zone, an increase of 10 microg/m3 in PM10 concentration increased
      the reporting of daily symptoms by 1.3. Multilevel analysis showed no statistical
      association between PM10 and respiratory symptoms, but asthma history, heavy
      traffic in front of the residence, presence of domestic pets, and dirt floors
      were associated with respiratory symptoms.

PMID- 20694368
TI  - [Prevalence of physical inactivity and associated factors among adolescents
      commuting to school].
AB  - The aim of this study was to verify the prevalence of physical inactivity and
      associated factors among adolescents commuting to school. This was an
      epidemiological study based on secondary data from a sample of 4,207 adolescents
      (14-19 years). Data were collected through a previously validated questionnaire
      (GSHS-WHO). Adolescents were classified as "inactive in commuting" when they
      reported not commuting to school actively (e.g., walking or bicycling) and/or
      spent less than 20 minutes getting to and from school. 43% (95%CI: 41.5-44.5) of
      adolescents were physically inactive in commuting. Place of residence and
      maternal schooling were statistically associated with outcome (inactivity in
      commuting to school) (p<0.01). Among male adolescents, physical inactivity in
      commuting was significantly associated with age (p=0.02) and skin color (p=0.04).
      Inactivity in commuting was relatively common when compared to other studies.

PMID- 20694369
TI  - Accuracy of a probabilistic record linkage strategy applied to identify deaths
      among cases reported to the Brazilian AIDS surveillance database.
AB  - Since record linkage errors can bias measures of disease occurrence and
      association, it is important to assess their accuracy. The aim of this study is
      to assess the accuracy of a multiple pass probabilistic record linkage strategy
      to identify deaths among persons reported to the Brazilian AIDS surveillance
      database. An HIV/AIDS national surveillance database (N=559,442) was linked to a
      total of 6,444,822 deaths registered (all causes) in the Brazilian mortality
      database. To estimate standard measures of accuracy, we selected all AIDS cases
      with a date of death registered in the surveillance database from 2002 to 2005
      (N=19,750) and 38,675 cases known to be alive in 2006. The linkage strategy
      presented a sensitivity of 87.6% (95%CI: 87.1-88.2), a specificity of 99.6%
      (95%CI: 99.6-99.7), and a positive predictive value of 99.2% (95%CI: 99.1-99.3).
      We observed a small variation in the validity measures according to some putative
      predictors of mortality. Our findings suggest that even large and heterogeneous
      databases can be linked with a satisfactory accuracy.

PMID- 20694370
TI  - Factorial validity and reliability of the General Health Questionnaire (GHQ-12)
      in the Brazilian physician population.
AB  - The 12-item General Health Questionnaire (GHQ-12) is a widely used screening
      instrument. One- and two-factor structures have been identified in some
      countries. In Brazil, the best factor structure is still unclear. This study
      aimed at knowing its factorial validity and reliability, and testing the one
      factor and two-factor models. The participants were 7,512 Brazilian physicians.
      They answered the GHQ-12 and demographic questions. Unrotated (one-factor) and
      rotated (two-factor) structures of the GHQ-12 were extracted by principal
      component analysis. Confirmatory factor analyses (ML) were used to compare the
      one- and two-factor solutions. The two-factor model fitted the data better than
      the one-factor one. Those two factors were depression and social dysfunction, and
      they showed themselves to be directly correlated to one another. They also showed
      adequate reliability coefficients. The two-factor model is remarkably adequate,
      showing better fit indices, although it is acceptable to admit a common factor,
      which could be defined as psychological distress.

PMID- 20694371
TI  - Mortality due to cancer of the uterine cervix in the state of Minas Gerais,
      Brazil, 1980-2005: period and cohort analysis.
AB  - This study identifies the period and cohort effects on the decreasing mortality
      trend of cancer of the uterine cervix and of the uterus, part unspecified, in the
      state of Minas Gerais, Brazil, during the period 1980-2005. 11,243 cases were
      included. A non-parametric method was used to calculate Z statistics and p
      values. The cohorts were assessed one by one and also in blocks of three, so as
      to allow for a larger number of comparisons to be made. Greater than expected
      mortality reduction was observed for the cohort blocks of women born in 1913
      1920; 1927-1936; 1937-1946; 1949-1956; 1963-1970; and 1969-1976. For the 1901
      1908 and 1921-1928 cohort blocks a smaller than expected mortality decrease was
      found. As for period effect, we found a greater than expected reduction for the
      2000-2001 period, in comparison with the previous one. The study suggests the
      existence of a significant cohort effect on mortality due to cancer of the
      uterine cervix in the study population, and such results have been placed in
      their social and political contexts.

PMID- 20694372
TI  - Survey of Brazilian governmental health agencies shows conflicting
      recommendations concerning oral hygiene practices for children.
AB  - The aims of this study were to detect whether recommendations concerning oral
      hygiene practices for children among Brazilian health agencies are consistent and
      to verify whether possible inconsistencies in these recommendations might be
      associated with an apparent gap in the scientific evidence. Fifty-four Brazilian
      health agencies were contacted by mail or electronic mail and were asked to send
      any material containing recommendations on oral hygiene practices aimed at
      children. A search was subsequently carried out on the Cochrane Oral Health
      Review Group and PubMed-Clinical Queries websites in order to assess the
      scientific evidence available on this subject. Forty (74%) agencies answered and
      21 materials containing oral hygiene recommendations were obtained. Eleven
      pertinent systematic reviews were identified. This preliminary study detected
      some conflicting and not evidence-based oral hygiene messages, which emphasizes
      the need to carry out and disseminate systematic reviews on these controversial
      issues in order to bridge the gap between knowledge and practice.

PMID- 20694373
TI  - [Guidelines for pregnancy in the woman with heart disease].

PMID- 20694393
TI  - Case 4/2010: seven-month-old female infant with transposition of the great
      arteries and subpulmonary ventricular septal defect (Taussig-Bing anomaly).

PMID- 20694394
TI  - Use of 6-minute walk test in pulmonary hypertension management.
AB  - The 6-minute walk test (T6) is used to assess cardiopulmonary diseases due to its
      prognosis capacity, easy performance and reproducibility. Pulmonary hypertension
      (PH) is defined and classified as a hemodynamic consequence leading to increased
      pulmonary arterial pressure and may result in right ventricular failure and
      consequent death. This case reports the prescription of T6 by the cardiology team
      at a university hospital as a means of physical control of a patient with HP,
      after the introduction and initiation of therapy.

PMID- 20694395
TI  - The cardiologist--a chained Prometheus.
AB  - This critical review discusses the deviations from the Flexnerian hegemonic model
      of medical practice, carried out under the point of view of paleomedicine and
      relevant evidence from research. If we, on the one hand, have the required and
      sufficient knowledge on the burden of diseases that afflict mankind and its
      determinant factors, on the other hand the attention turns to strategies that do
      not have an effective impact on such diseases, consuming a larger portion of
      resources directed to healthcare: ischemic cardiovascular diseases, followed by
      type 2 diabetes mellitus. Their risk factors are well-known and have been shown
      to be controllable through health promotion actions, which constitute a process
      technology that is more cost-effective than biotechnology. However, we choose to
      apply large part of the financial resources on the care of the affected
      individual to the detriment of health promotion in the general population, who
      goes without this benefit, which characterizes an injustice in terms of
      healthcare actions.

PMID- 20694396
TI  - Anthropometric indicators of insulin resistance.
AB  - Some studies have analyzed the efficacy of anthropometric indicators in
      predicting insulin resistance (IR), for they are more economic and accessible. In
      this study, the objective was to discuss the measures and anthropometric indices
      that have been associated with IR. A bibliographic review was done, based on
      Scielo, Science Direct and Pubmed. Among these studies, waist and sagittal
      abdominal diameter presented better predictive capacity for IR, with more
      consistent results. The waist-to-thigh, waist-to-size, neck-to-thigh ratios, the
      conicity and the sagittal index have showed positive results; nevertheless, more
      studies are necessary to consolidate them as predictors to IR. The obtained
      results, with the use of body mass index and of the waist-to-hip ratio, were
      inconsistent. In the Brazilian population, the realization of studies evaluating
      the performance of these indicators in predicting IR is suggested, since the
      results of the studies conducted in other populations are not always applicable
      to ours, due to ethnic differences resulting from the great miscegenation in the
      country.

PMID- 20694397
TI  - Noncompaction of the myocardium, Chagas' disease and dysfunction: a case report.
AB  - We report the association between heart disease associated with noncompaction of
      the left ventricular myocardium (NCLVM) and chronic Chagas' heart disease (CCHD)
      in a patient with heart failure, ischemic stroke and cardiac arrhythmia. Images
      typical of NCLVM and CCHD were documented by cardiac magnetic resonance imaging
      (CMRI).

PMID- 20694398
TI  - The impact of continuous positive airway pressure (CPAP) on the cardiac
      rehabilitation of patients with congestive heart failure: case report.
AB  - Congestive heart failure is a pathology that limits the patient's physical
      function. This study analyzed one patient who was submitted to a cardiac
      rehabilitation program associated to Continuous Positive Airway Pressure (CPAP),
      by assessing the results of the six-minute walk test (6MWT) and a questionnaire
      on the quality of life and performing an echocardiographic assessment before the
      study and after six weeks. The distance walked by the patient increased from
      152.5 m to 520.44 m at the 6MWT. The Minnesota questionnaire score decreased from
      62 to 18. Ejection fraction increased from 33% to 36%. Therefore, the management
      chosen for this case improved the patient's physical performance and quality of
      life.

PMID- 20694399
TI  - The Archives and the publication of its first impact factor.

PMID- 20694400
TI  - Real-world use of drug-eluting stents: the importance of registries.
AB  - Over the last decades the efficacy and safety of bare metal (BMS) and drug
      eluting stents (DES) have been demonstrated in many different clinical scenarios,
      leading to their use in more than 75% of the procedures worldwide. Compared to
      BMS, DES have shown lower rates of angiographic restenosis and target-vessel
      revascularization. This benefit was initially demonstrated in trials that
      excluded patients with more complex lesions, such as those with larger or smaller
      vessels, chronic total occlusions, bifurcation lesions, stent restenosis, long
      lesions and left main coronary artery disease. This real-world population has
      been recently evaluated in many registries and meta-analyses that are reviewed
      herein.

PMID- 20694401
TI  - Effects of resistance training on blood pressure in the elderly.
AB  - The aging process drastically reduces muscle mass, strength and power, decreasing
      the capacity to perform the activities of daily living. The practice of
      resistance exercises can reverse this picture, helping to maintain the muscular
      mass and improving muscular strength and resistance. However, the aging process
      causes cardiovascular alterations, which can result in increased blood pressure
      levels at rest and it is important to analyze the effects of resistance exercises
      on the blood pressure of elderly individuals. The objective of this study is to
      evaluate the current scientific knowledge on the responses of the blood pressure
      to resistance exercises and their mechanisms in elderly individuals. In order to
      do that, we carried out a literature review related to the theme, in both
      Portuguese and English. Based on the studies found, the current corpus, although
      scarce and controversial, suggests that, chronically, resistance exercises can
      have a hypotensive effect on elderly individuals. However, this effect occurs
      mainly in normotensive elderly individuals submitted to low-intensity training.
      The mechanisms involved in the hypotensive response still need to be clarified.
      Although the resistance training is recommended for elderly individuals and there
      is some evidence that it can have a chronic hypotensive effect, there is still
      lack of scientific data and much debate on the subject, which demonstrates that
      this field is still open to investigation.

PMID- 20694402
TI  - [Small for gestational age infants: need for medical follow-up during all the
      period of growth].

PMID- 20694403
TI  - The difficult patient: drug interaction and the influence of concomitant diseases
      on the treatment of hypothyroidism.
AB  - Although most hypothyroid patients do well with one single tablet of thyroxine
      daily, approximately 10% are dissatisfied and another important group of patients
      is difficult to control. We reviewed the most common causes for frequent-dose
      adjustment or high-dose requirement, including poor compliance with therapy and
      inadequate medication. Since these two causes have been ruled out, drug
      interaction and other concomitant diseases need to be investigated. Requirements
      of thyroxine increase in all conditions characterized by impaired gastric acid
      secretion. Proton-pump inhibitors, antacids and a long list of drugs may decrease
      thyroxine absorption. In addition, a series of diseases including celiac disease
      and chronic inflammatory intestinal diseases, as well as nutritional habits may
      be important in patient control. Finally, we mention the effects of a growing
      list of drugs and thyroid disruptors that may also affect thyroid hormone
      metabolism at many levels.

PMID- 20694404
TI  - [Clinical predictors of growth response in the first year of treatment with a
      fixed dose of growth hormone in children born small for gestational age].
AB  - OBJECTIVE: To identify clinical predictors associated with catch-up growth in the
      first year of treatment with somatropin (rhGH) in a group of children born small
      for gestational age (SGA). SUBJECTS AND METHODS: Thirty nine children who have
      been on rhGH therapy for at least one year (0.33 mg/kg/week) were evaluated. The
      clinical parameters analyzed were chronological age (CA), bone age (BA), target
      height and standard deviations scores (SDS) of birth weight and length, height,
      weight and growth rate. RESULTS: rhGH therapy was associated with a first year
      height increment of 0.67 SDS (p < 0.01). BA and birth weight SDS were predictive
      of growth response, with statistical difference in height SDS variation between
      prepubertal and pubertal subgroups (p = 0.016). CONCLUSION: These data show a
      significant growth response with a fixed rhGH dose, those children who started
      rhGH in prepubertal ages presented the best outcomes.

PMID- 20694405
TI  - [GADA persistence and detectable C peptide in patients with long standing
      diabetes mellitus type 1].
AB  - OBJECTIVE: The aim of this study was to evaluate if GADA+ and detectable CP had
      any influence in other autoimmune diseases, glycemic control, and risks of
      retinopathy in diabetes mellitus type 1 (T1DM) lasting longer than 3 years of
      duration. SUBJECTS AND METHODS: Fifty T1DM subjects were interviewed, performed
      fundoscopic examination, and measured CP before and after glucagon, HbA1C, and
      GADA. RESULTS: GADA+ (n = 17) had a higher frequency of other autoimmune diseases
      when compared to GADA (p = 0.02). Detectable CP was also associated with a higher
      prevalence of these diseases (p = 0.03), although, retinopathy was not influenced
      by either one. Detectable CP had no influence in the glycemic control (mean
      HbA1C) (p = 0.28). However, insulin daily doses were lower in this group (0.62
      vs. 0.91 U/kg/day; p = 0.004). CONCLUSION: Although not recommend as a marker of
      other autoimmune diseases, GADA+ seems to be not only a pancreatic autoimmunity
      signal. Detectable CP may also have some promising influence in detecting these
      diseases. Neither influenced the presence of retinopathy, but insulin daily
      requirements were smaller when CP was present.

PMID- 20694406
TI  - [Consumption of sweeteners and dietetic foods by individuals with type 2 diabetes
      mellitus, assisted by the National Health System in Ribeirao Preto, SP].
AB  - OBJECTIVE: To analyze the consumption of sweeteners and dietetic foods by
      individuals with type 2 diabetes, assisted by the Brazilian National Health
      System, in the city of Ribeirao Preto, SP. SUBJECTS AND METHODS: Through a
      questionnaire were interviewed 120 patients were interviewed, stratified by sex,
      age and level of health care. RESULTS: The use of sweeteners is very frequent by
      the population in study, with predominance of the liquid type, and the use of
      dietetic foods is less common, with predominance of soft drinks. The diagnosis of
      diabetes was determinant for starting the use of both and the used criterion for
      selection of the sweetener is its flavor. The percentage of the population that
      knows the difference between diet and light products, that has the habit to read
      labels, and that is worried with the amount used of sweetener, is small.
      CONCLUSION: There is a need to include information about the adequate use of
      these products in the health care activities for patients with diabetes in the
      different levels of the Brazilian National Health System.

PMID- 20694407
TI  - [Effect of n-3 fatty acids in glycemic and lipid profiles, oxidative stress and
      total antioxidant capacity in patients with the metabolic syndrome].
AB  - OBJECTIVE: Metabolic syndrome (MS) is a cluster of factors which favors the
      development of cardiovascular diseases. Previous studies have shown that
      polyunsaturated fatty acids (PUFAs) can improve some of these factors. This study
      aimed to evaluate the effect of fish oil on glucose and lipid profiles, oxidative
      stress and total antioxidant capacity (TRAP) in patients with MS. SUBJECTS AND
      METHODS: We conducted a clinical trial in 40 patients with the MS (20 controls
      and 20 patients receiving 3 g/day of PUFAs). SUBJECTS AND RESULTS: The group that
      received treatment showed a significant decrease in levels of triglycerides and
      increased in TRAP, but they had a significant increase in LDL, glucose and
      insulin resistance. CONCLUSION: We conclude that intake of fish oil resulted in
      decreased levels of triglycerides and increased the TRAP of patients with MS;
      however, increased LDL levels and insulin resistance, were observed.

PMID- 20694408
TI  - [Characterization of metabolic resting rate and proposal of a new equation for a
      female Brazilian population].
AB  - OBJECTIVES: The goals of this study were to standardize resting metabolic rate
      (RMR) in the Brazilian female population and evaluate the suitability of the HB
      equation. SUBJECTS AND METHODS: In order to do so, 760 indirect calorimetry (CI)
      measurements performed in Brazilian female patients between 18 and 65 years old,
      were used. The results were tabulated, the population distributed according to
      the quintiles of weight, and the statistical analyses applied. RESULTS: The
      average RMR varied from 1,226 to 1,775 calories/day. The HB equation
      overestimated the RMR by about 7%. From the correlation between the variables, we
      conclude that weight has a positive correlation with RMR and age a negative
      correlation. CONCLUSION: The RMR and respiratory quotient (QR) can be used as
      obesity predictors. Two new equations were proposed in our study, one for the
      population with body mass index (BMI) > 35 kg/m(2) and another for the population
      with BMI < 35 kg/m(2).

PMID- 20694409
TI  - Normal values of serum IGF-1 in adults: results from a Brazilian population.
AB  - OBJECTIVE: To determine the normal values of serum IGF-1 (Immulite 2000) in a
      Brazilian adult (21-70 years) population. SUBJECTS AND METHODS: Healthy
      volunteers were divided into 10 groups according to age (5-year intervals), with
      100 subjects (50 men and 50 women) per group. One-hundred participants were
      selected for repetition of the test after 12 weeks. RESULTS: No difference in IGF
      1 values was observed between men and women, but a progressive reduction of serum
      IGF-1 with age was seen. The reference values provided by the manufacturer of the
      assay, although discretely higher, were very close to the values found in this
      study. A second measurement of IGF-1 after 12 weeks revealed a variation < 20% in
      99% of subjects. CONCLUSIONS: This study established the reference range for IGF
      1 determined with the Immulite 2000 assay for a large number of healthy Brazilian
      adults stratified according to age, and suggests that variations > 20% in IGF-1
      levels within an interval of 12 weeks cannot be attributed to interassay
      variability.

PMID- 20694410
TI  - Molecular analysis of the PROP1 and HESX1 genes in patients with septo-optic
      dysplasia and/or pituitary hormone deficiency.
AB  - OBJECTIVE: The present study aimed at evaluating the PROP1 and HESX1 genes in a
      group of patients with septo-optic dysplasia (SOD) and pituitary hormone
      deficiency (combined - CPHD; isolated GH deficiency - GHD). Eleven patients with
      a clinical and biochemical presentation consistent with CPHD, GHD or SOD were
      evaluated. SUBJECTS AND METHODS: In all patients, the HESX1 gene was analyzed by
      direct sequence analysis and in cases of CPHD the PROP1 gene was also sequenced.
      RESULTS: A polymorphism (1772 A > G; N125S) was identified in a patient with SOD.
      We found three patients carrying the allelic variants 27 T > C; A9A and 59 A > G;
      N20S in exon 1 of the PROP1 gene. Mutations in the PROP1 and HESX1 genes were not
      identified in these patients with sporadic GHD, CPHD and SOD. CONCLUSION: Genetic
      alterations in one or several other genes, or non-genetic mechanisms, must be
      implicated in the pathogenic process.

PMID- 20694411
TI  - Is there a link between glucose levels and heart failure? An update.
AB  - It has been well documented that there is an increased prevalence of standard
      cardiovascular (CV) risk factors in association with diabetes and with diabetes
      related abnormalities. Hyperglycemia, in particular, also plays an important
      role. Heart failure (HF) has become a frequent manifestation of cardiovascular
      disease (CVD) among individuals with diabetes mellitus. Epidemiological studies
      suggest that the effect of hyperglycemia on HF risk is independent of other known
      risk factors. Analysis of datasets from populations including individuals with
      dysglycemia suggests the pathogenic role of hyperglycemia on left ventricular
      function and on the natural history of HF. Despite substantial epidemiological
      evidence of the relationship between diabetes and HF, data from available
      interventional trials assessing the effect of a glucose-lowering strategy on CV
      outcomes are limited. To provide some insight into these issues, we describe in
      this review the recent important data to understand the natural course of CV
      disease in diabetic individuals and the role of hyperglycemia at different times
      in the progression of HF.

PMID- 20694412
TI  - Pituitary gland metastasis from renal cell carcinoma presented as a non
      functioning macroadenoma.
AB  - Metastatic tumors involving the pituitary gland are an uncommon finding and occur
      in up to 1% of all pituitary tumor resections. A 74-year-old man had progressive
      vision deterioration, over the 30 days prior to consultation. He did not complain
      of headache or polyuria, but referred to intestinal constipation. Five years ago,
      he underwent a right radical nephrectomy for renal cell carcinoma, followed by
      chemotherapy and radiotherapy for lung and parotid metastases. On ophthalmologic
      examination, there was a left abducens nerve palsy and bitemporal hemianopia.
      Magnetic resonance imaging demonstrated a sellar mass with suprasellar cistern
      extension compressing the optic chiasm. Endocrinological evaluation revealed
      central adrenal and gonadal insufficiencies. The patient underwent a
      transsphenoidal tumor resection that revealed renal cell carcinoma. This case
      illustrates that metastatic pituitary lesions can mimic typical symptoms and
      signs of pituitary macroadenoma. Furthermore, clinical diabetes insipidus, a
      common finding of pituitary metastases, can be absent.

PMID- 20694413
TI  - Long term treatment of a thyrotropin-secreting microadenoma with somatostatin
      analogues.
AB  - Thyrotropin (TSH) secreting pituitary adenomas (TSH-omas) account for < 1% of all
      pituitary adenomas and are a rare cause of hyperthyroidism. The diagnosis is
      often made at the stage of macroadenoma because of the aggressive nature of the
      tumor and due to the fact that patients are mistakenly treated for more common
      primary hyperthyroidism for a long time. First line therapy is transsphenoidal
      resection of the tumor, which can cure one-third of the patients completely.
      However, if surgery is not possible or curative, pituitary radiotherapy and/or
      somatostatin analogs (SSA) can be useful. We report the case of a 54-year-old
      woman treated 20 years earlier for a mistakenly suspected primary
      hyperthyroidism. Given the persistence of symptoms she was studied further and
      was diagnosed with a thyrotropinoma. Despite the delay in diagnosis and prior
      thyroid ablation, a microadenoma was found. As transsphenoidal surgery was not
      considered effective, medical therapy with a somatostatin analogue was initiated.
      Currently, at four years of follow-up, the patient continues on this treatment
      and remains euthyroid and asymptomatic. We report a case of successful long-term
      treatment with SSA, after unsuccessful surgery.

PMID- 20694414
TI  - Nadir growth hormone after oral glucose overload in obese subjects.

PMID- 20694415
TI  - [Summarizing the results of the studies on the drug phenomenon].

PMID- 20694416
TI  - [Alcohol consumption in administrative and service personnel in an Ecuadorian
      university].
AB  - The aim of this descriptive study was to characterize the consumption of alcohol
      among workers in the administrative and service sectors at an Ecuadorian
      university and to determine differences in consumption between the two groups of
      workers. The Alcohol Use Disorders Identification Test (AUDIT) was applied to 102
      participants. The results showed that the service personnel consumed more alcohol
      than the administrative personnel with a mean total score of 7.26 against 1.84.
      The total prevalence of non-prejudicial consumption was 79.41%, prejudicial
      consumption 19.61% and dependency 0.98%. The total scores of 76.47% of the
      participants were within risk zone one; 18.63% risk zone two; 3.92% risk zone
      three; 0.98% risk zone four. In conclusion, due to the identification of
      hazardous consumption, it is necessary to implement a program of alcohol use
      prevention in the institution studied.

PMID- 20694417
TI  - [Alcohol consumption and stress in second year nursing students].
AB  - The aim of this study was to identify the consumption of alcohol and academic
      stress in nursing students. This was a descriptive, cross-sectional study,
      performed in 2005. The questionnaires Academic Stress Inventory and AUDIT were
      applied to 82 students of a private University in Lima, Peru. The students had a
      mean age of 20.4 years, 92.7% were single, 69.5% did not work, 91.5% had no
      children and 86.6% lived with their parents. The academic overload represented
      the stressor of highest prevalence. Regarding the consumption of alcohol, 56.1%
      consumed alcohol once a month, 48.0% consumed 1-2 glasses a day, and 51.2% more
      than three glasses during a normal day; 11.0% failed to comply with their
      obligations. One third reported smoking, drinking or eating in excess. All
      situations, related to the factor activity/time, generated various levels of
      stress, with worry reported as the main response to stress.

PMID- 20694418
TI  - [Protective factors for preventing the use of drugs in the families of a Colombia
      locality].
AB  - The aim of this study was to analyze the protective factors that prevent drug use
      in the families of children who attend Community Homes of Family Well-being in a
      small Colombian locality. This was a quantitative, descriptive, transversal
      study, with 256 families constituting the sample. Data were collected through a
      self-applied questionnaire throughout March and April 2007. Protective factors
      found included demonstrations of affection toward the children, playing with them
      and talking to them about things they like, open communication, decision making
      as a couple, flexibility of the nursing process, and establishment of rules.
      However, some risk factors were also found, such as consumption of legal drugs
      such as cigarettes and alcohol, and in a low percentage, consumption of illicit
      drugs. A high percentage of families consider that drug use must be prevented in
      the first years of life, by the parents. The protective factors found require
      reinforcement as they are not very strong, and the risk factors must be
      controlled to turn them into protective factors.

PMID- 20694419
TI  - [Alcohol use and traffic accidents: a study of alcohol levels].
AB  - This was an exploratory, descriptive study that aimed to correlate alcohol levels
      detected in fatal victims of traffic accidents, in Rio de Janeiro city, with the
      victims profile and the characteristics of the accident. The data were retrieved
      from the registers of the Legal Medicine Institute/IML, through the registers of
      the medical records of the fatal victims of traffic accidents. Compiled and
      tabulated using the Statistics Program SPSS, for the period between January and
      May 2005, 348 fatal victims of traffic accidents were reported. Of these victims,
      94 had been tested for alcohol, of these, 83 had levels of alcohol detected,
      60.2% presented levels above 0.6g/l blood. The use of alcohol was evident, at
      levels above and below 0.6g per liter of blood, in the cases of fatal victims of
      traffic accidents.

PMID- 20694420
TI  - [Accidents and injuries due to consumption of alcohol or drugs in patients
      treated at an emergency room].
AB  - The aims of the study were to describe the differences in alcohol consumption by
      sex, education and occupation and to understand the effects of the socio
      demographic characteristics on alcohol consumption, in 120 emergency room
      patients. The results showed significant differences for sex (t=-3.570, p <.01)
      and education (t=2.636, p <.01) in alcohol consumption. In addition the factors;
      age, age alcohol consumption started, quantity of alcohol ingested, age marijuana
      consumption started, and hours lapsed between the consumption of marijuana and
      the accident (F(7, 116)=15.519, p <.00), were also significant on the consumption
      of alcohol with an explained variance of 40%.

PMID- 20694421
TI  - [Nursing students knowledge about alcohol and drugs].
AB  - The aim of this study was to verify the knowledge of nursing students regarding
      the use of alcohol and other drugs, particularly addiction, tolerance, withdrawal
      and intoxication, the reasons students give for drug addiction and commencement,
      and personal interest in the issue of drug use. A descriptive-exploratory design
      was used, with a sample of 44 students, by applying a semi-structured
      questionnaire, constructed by the researchers based on the objectives, with open
      and closed questions, totaling 24 points. Ethical procedures were followed and
      data were submitted to exploratory descriptive analysis. It was shown that
      students knowledge is still limited, comprehension about a patients reasons for
      using and becoming addicted is incomplete and the interest is current.

PMID- 20694422
TI  - [Characterization of students of the nursing degree course and their perceptions
      about licit and illicit drug consumption].
AB  - This was a quantitative, descriptive, cross-sectional study. The participant
      population consisted of 69 students who were attending the fifth year of the
      Nursing Degree course. A self-administered questionnaire was applied, which was
      previously validated with a sample of nursing students that were attending other
      years of the course. The instrument was divided into five domains: general,
      sociodemographic, economic, personal, familiar and sociocultural information. The
      study evidence, that the phenomenon of drugs is multifactorial, is associated
      with sociodemographic, economic, personal, familiar and sociocultural
      characteristics. The students were predominantly female, of the middle-economic
      class, with good academic performance, but had unhealthy life styles. Concerning
      drug consumption, 44.9% had consumed alcoholic beverages and consumed at the time
      of the study, another smaller percentage smoked tobacco and 1.4% smoked
      marijuana; in addition, a clear knowledge of risk behaviors and of the
      consequences to which they are exposed did not exist within this group.

PMID- 20694423
TI  - [Care for family caregivers living with alcoholics through the problem solving
      technique].
AB  - The aim of this study was to offer training to family caregivers of alcoholic
      patients through the problem solving technique. This was a descriptive study, in
      which eight family caregivers participated. Three meetings were held, which
      addressed themes such as: behavioral changes and exhaustion of those giving care.
      From these meetings, feelings emerged which were mobilized by the situation of
      behavioral changes; self care of the caregiver by sharing responsibilities with
      relatives and other people and the search for specialized care. Study
      participants considered the proposed intervention as positive, since it allowed
      them to reflect on their experiences and their potential to cope with
      difficulties. It is believed that nurses trained for care delivery to family
      caregivers should explore this area.

PMID- 20694424
TI  - [Smoking among nurses of the national hospital in Lima, Peru].
AB  - Nurses have unique opportunities to help their patients to stop smoking. The aim
      of this study was to identify, among nurses of a hospital, the consumption of
      smoking products, their attitudes and information received on smoking. It was a
      descriptive study, carried out with 204 (48%) nurses of the Hospital Arzobispo
      Loayza, Lima, Peru. The Global Health Professional Survey (GHPS) was used. Among
      the sample the prevalence of smoking in life was 67.1% and 3% in the last month.
      The majority of nurses presented positive attitudes and knew the importance and
      responsibility of advising patients to quit. The majority had received general
      information regarding the topic, though half of them had not received specific
      information regarding treatment. In view of the importance of this theme, this
      study identified a need for further research of this nature as well as revision
      of the curricula regarding the approach toward the theme of smoking.

PMID- 20694425
TI  - [Alcohol consumption and domestic violence against women: a study with university
      students from Mexico].
AB  - Domestic violence against women and alcohol consumption are considered public
      health problems. This descriptive study aimed at determining the occurrence of
      domestic violence against women enrolled in the Nursing and Midwifery Program at
      the University of Celaya, Mexico and its relation with alcohol consumption by
      their partners. A sample of 73 students was randomly selected. Data were
      collected using the CASIQUE-QUEJ TUN questionnaire and analyzed using SPSS. With
      respect to physical violence, results showed that 91.9% were not maltreated by
      their partners. Regarding alcohol consumption, 57.5% of the women interviewed and
      67.1% of their partners drank alcohol, especially at social events. Results also
      showed that 41.1% of the subjects did not know about their rights in cases of
      domestic violence. Thus, there is a need for actions which increase women's
      awareness of their rights and the possibilities of legal support in cases of
      violence.

PMID- 20694426
TI  - [Characterization of the students of a nursing course regarding the consumption
      of licit and illicit drugs].
AB  - The aim of this quantitative, descriptive, transversal study was to characterize
      drug use among students in the second year of the Nursing Degree course. The
      sample of 119 students answered a questionnaire divided into: general
      information, sociodemographic, economic, personal, familiar, sociocultural and
      drug usage. The study showed that students possess factors that protect them from
      drug usage and the acquisition of drug habits; but that they also have risk
      factors which must be taken into consideration in prevention programs, such as
      unhealthy life styles or drug abusage in people close to them (family, friends or
      classmates). We found that the profile of drugs used, containing both legal and
      illegal drugs, was similar to those in the national and international context. It
      is important to emphasize that even though the consumption of alcohol and tobacco
      occupy the highest places, in the student environment as well as nationally,
      these are not considered as problematic as the illegal drugs.

PMID- 20694427
TI  - [Roles of professionals in drug outpatient care centers, in the city of Bogota,
      Colombia].
AB  - The aim of this descriptive, cross-sectional study, developed with 93
      professionals, was to characterize the roles of the professionals who were
      working in the drug addiction outpatient centers of the city of Bogota, Colombia.
      The results showed that psychologists were the predominant professionals (38%),
      followed by occupational therapists (34%). Nurses corresponded to 8% of the
      professionals, with their roles predominantly in the aspects of health promotion
      and self care (100%), in the administrative area (43%) and in prevention (57%)
      and very little in rehabilitation and social rehabilitation (14%). The roles of
      the professionals agreed with the expected activities of the different
      professions, with the exception of the occupational therapists. It is considered
      that nurses need to gain more space within the team to focus on drug users.

PMID- 20694428
TI  - [Knowledge and practice regarding tobacco use among pharmacy undergraduate
      students in Lima, Peru].
AB  - The aim of this study was to determine the knowledge and the practices regarding
      tobacco consumption in pharmacy students according to their demographic and
      academic characteristics. The sample consisted of 276 (55.2%) pharmacy students
      of a Peruvian Private University to whom the Global Youth Tobacco Survey (GYTS)
      was applied. In men, the prevalence of lifetime use of tobacco of 93.7%, of
      alcohol 70.8% and of illegal drugs 14.1% was identified. The prevalence of
      lifetime and current consumption of tobacco in the sample was very high. The
      majority of students began using drugs at 16 years old. There was a strong
      association between the consumption of tobacco and the fact that at least one of
      the parents smoked and the exposure to smoke inside the home.

PMID- 20694429
TI  - [An attractive force: the meaning of drugs to users from an island in Cape
      Verde].
AB  - This qualitative study aimed to understand the meaning of drug consumption from
      the view of users who receive care in an outpatient clinic of a Mental Health
      Service on an island of the Cape Verde archipelago. The methodological framework
      was based on the Data-founded Theory, in the light of Symbolic Interactionism.
      Participants were nine drug users from the mentioned outpatient clinic. Recorded
      interviews and observation were the strategies for data collection. The
      comparative data analysis resulted in the central phenomenon An attractive force,
      which expresses the great difficult users have to stop the abusive consumption of
      psychoactive substances, knowing that all problems faced in the personal,
      familiar and social areas come from drug habituation. Thus, this study permitted
      the identification of vulnerable points for possible action by the health team,
      aiming for the prevention of drug abuse.

PMID- 20694430
TI  - [Drug consumption in young people in Guayaquil City, Ecuador].
AB  - This study aimed to characterize the predominant causes and the types of drugs
      consumed among young people between 10 and 18 years old at an institution that
      receives young lawbreakers in an Ecuadorian city. A descriptive and qualitative
      study was carried out, using individual and semi-structured interviews as the
      main source of data collection. Ten young people between 10 and 16 years old
      participated. Content analysis resulted in three themes: lack of family support,
      influence from the environment where young people develop and ignorance about the
      side effects drugs produce and plans for the future. Marijuana was identified as
      the most consumed drug, followed by alcohol and inhaled drugs. Exploration of the
      causes that make these young people consume drugs contributes to identifying
      their needs and creating important spaces for health care, particularly health
      promotion.

PMID- 20694431
TI  - [Drug use among students of the Faculty of Medical Sciences of the National
      Autonomous University of Nicaragua, Leon, Nicaragua].
AB  - The aim of this study was to characterize the relationships of students of the
      Faculty of Medical Sciences of UNAN Leon, with licit and illicit drugs. This was
      accomplished by means of a traversal, descriptive study carried out in the year
      2008 in the City of Leon, Nicaragua. The SAMSHA (Substance Abuse and Mental
      Health Services Administration) questionnaire, adapted for the Nicaraguan
      context, was applied anonymously. The questionnaire was completed by a total of
      954 students, between 17 and 35 years old, of both sexes. It was found that 52.6%
      of the students used alcohol, 25.3% tobacco, 48.7% medication and 2.6% cocaine.
      It is necessary to develop other studies to guide prevention and intervention in
      the university context.

PMID- 20694432
TI  - [Traffic accidents and alcohol consumption in an emergency unit of La Paz,
      Bolivia].
AB  - The aim of this quantitative, descriptive, observational, cross-sectional study
      was to characterize the distribution and characteristics of motor vehicle
      accidents related to alcohol consumption. The sample was composed of 62 drivers
      and pedestrians, over 15 years old, who were involved in motor vehicle accidents
      involving alcohol, and were attended at the Emergency Unit of the Clinical
      Hospital of La Paz - Bolivia. A survey designed by the researchers to collect
      partner-demographic data and morbidity of the victim was applied and data that
      evaluated the alcohol consumption of the driver responsible for the accident was
      collected. The results demonstrated that 71% of the victims were men; 32.3% were
      between 21 and 30 years old; 29% were students and 25.8% were the drivers. This
      study shows the characterization of victims, alcohol consumption and accidents.

PMID- 20694433
TI  - [Assessment of alcohol use in families of the suburbs of Guayaquil City, Ecuador,
      by nursing students].
AB  - The aim of this study was to present the demographic and alcohol use profiles of
      families assessed by nursing students during the Community and Family Nursing
      Program. This is a case study using The family assessment questionnaire as its
      data source, which was applied by nursing students to assess family health
      conditions, during their practical training. Family selection was by convenience
      according to risk indicators and poverty, assessed from the outside condition of
      the dwelling or from public health services records of the area. A questionnaire
      correlated with the one that students applied was prepared to obtain data. This
      instrument obtained information about the socioeconomic profile, family
      environment and alcohol consumption. The Alcohol Use Disorder Identification Test
      (AUDIT) was applied to families that reported alcohol use. Of the 128 families
      evaluated by students we found 47 families who reported alcohol consumption,
      these families answered AUDIT, the average total score was 10.66 which equates to
      risk level 2. The suggested intervention for this level of risk is simple
      counseling that can be offered by nurses in the primary health care.

PMID- 20694434
TI  - [The discourse on alcohol in the Brazilian Journal of Nursing: 1932-2007].
AB  - This was a literature review study which examined the theme of alcohol in the
      papers of the Brazilian Journal of Nursing, from 1932 to 2007. A manual search
      was performed using the keywords: alcohol, alcoholism, drugs and psychoactive
      substances. The discourse on alcohol, used by the authors, was analyzed according
      to the methodological proposals of Bardin. Eight papers were found that showed
      three categories: biopsychosocial aspects, conceptions of alcohol and alcoholism,
      and image of the alcoholic. The study shows how the discourse on alcohol and
      alcoholism has progressed from common sense to scientific status, corresponding
      to the historical moment of its production.

PMID- 20694435
TI  - [Alcohol consumption and self esteem in adolescents].
AB  - The aim of this study was to analyze the relationship of levels of self esteem
      and alcohol consumption in adolescents, by carrying out a transversal,
      descriptive study, in a college of nursing of Queretaro in Mexico, in the month
      of July 2008, with a sample of 109 adolescents, between 17 and 20 years old. For
      attainment of the data two instruments were applied: AUDIT and the Rosemberg self
      esteem scale. The majority of the participating adolescents had high self esteem
      (94.5%) and none presented low self esteem. Of the adolescents in the study 80.7%
      did not consume alcohol hazardously. It was concluded that the adolescents
      presented high self esteem and low alcohol consumption. Therefore, it is
      necessary to implement preventive programs related to alcohol consumption and to
      identify the protective factors to guarantee the maintenance of healthy habits
      for the adolescents.

PMID- 20694436
TI  - [Meanings about smoking for women participant in a group for smokers].
AB  - The aim of this study was to understand the meanings produced about smoking by
      women participating in a group for smokers in Florianopolis, SC, Brazil. Seven
      participants took part in structured interviews with five open questions. The
      theoretical framework was social constructionism with two themes: 1) Cigarettes
      in the women's life cycle 2) Expectations regarding treatment. The repertories
      used to describe the beginning of consumption in adolescence included glamour,
      charm, independence and peer acceptance and those used to describe the
      maintenance of consumption in adulthood included anxiety, depression and coping
      with daily stress. Regarding expectations for treatment they believed that
      contact with people who experience the same difficulties in relation to the
      cessation of consumption and the dream of a healthy life would be motivating. The
      treatment offered to smokers should explore strategies for women to achieve what
      they want regarding the consumption of cigarettes.

PMID- 20694437
TI  - [Analysis of the frequency of experimentation with and consumption of drugs in
      high-school students].
AB  - The aim of this study was to survey the frequency of experimentation and
      consumption of drugs in high-school students in Cordoba, Argentina, relating it
      to socio-demographic variables. An observational-analytical method was employed,
      on the basis of the records of the Secretary for the Planning of Drug-Addiction
      Prevention and Fighting of Drug-Trafficking. Statistical. Bivariate analysis,
      odds ratio and confidence interval were applied in the processing of each
      variable. Alcohol consumption was found to be more frequent among males. Of the
      subjects 12.2% had tried some type of illicit substance. Tranquilizers were the
      most commonly used psycho-medicine. Drug consumption increased with age, years of
      schooling and availability of money. Our detection of an epidemiological
      situation is deemed useful for prevention strategies for drug addiction among
      teenagers.

PMID- 20694439
TI  - Validity of the Mood Disorder Questionnaire in a Brazilian psychiatric
      population.
AB  - OBJECTIVE: Bipolar spectrum disorders are prevalent and frequently underdiagnosed
      and undertreated. This report describes the development and validation of the
      Brazilian version of the Mood Disorder Questionnaire, a screening instrument for
      bipolar spectrum disorders, in an adult psychiatric population. METHOD: A total
      of 114 consecutive patients attending an outpatient psychiatric clinic completed
      the Brazilian version of the Mood Disorder Questionnaire. A research
      psychiatrist, blind to the Mood Disorder Questionnaire results, interviewed
      patients by means of the mood module of the Structured Clinical Interview for DSM
      IV ('gold standard'). RESULTS: The internal consistency of the Brazilian Mood
      Disorder Questionnaire, evaluated with Cronbach's alpha coefficient was 0.76 (95%
      CI; 0.69-0.92). Principal component analysis with varimax rotation indicated an
      'irritability-racing thoughts' factor and 'energized-activity' factor, which
      explained 39.1% of variance. On the basis of the SCID, 69 (60.5%) individuals
      received a diagnosis of bipolar disorders. A Brazilian Mood Disorder
      Questionnaire screening score of 8 or more items yielded sensitivity of 0.91 (95%
      CI; 0.85-0.98), specificity of 0.70 (95% CI; 0.62-0.75), a positive predictive
      value of 0.82 (95% CI; 0.75-0.88) and a negative predictive value of 0.84 (95%
      CI; 0.77-0.90). CONCLUSION: The present data demonstrate that the Brazilian Mood
      Disorder Questionnaire is a valid instrument for the screening of bipolar
      disorders. The instrument needs to be validated in other settings (e.g., in
      general practice).

PMID- 20694438
TI  - [Self-efficacy and attitudes towards drug consumption in childhood: exploring
      concepts].
AB  - This paper aims to explore the concepts of self-efficacy and attitude towards
      consumption, approached by the theory of motivation and human behavior. This is a
      theoretical study based on literature. High levels of self-efficacy have
      beneficial consequences for the functioning of the individual. Concerning
      attitudes towards drugs, the presence or absence of preconceptions and positive
      values of drugs increases risk or consumer protection. Nurses should apply the
      concepts of self-efficacy and attitudes towards consumption to guide actions of
      health promotion and prevention of drug consumption in children and adolescents.

PMID- 20694442
TI  - Depressive symptoms in rheumatoid arthritis.
AB  - OBJECTIVE: To determine the prevalence of depressive and anxiety symptoms in
      patients with rheumatoid arthritis (a chronic inflammatory disease) in comparison
      to a control group with osteoarthritis (a chronic non-inflammatory degenerative
      disease) and to identify the sociodemographic and clinical variables associated
      with depressive symptoms in these patients. METHOD: Sixty-two rheumatoid
      arthritis patients and 60 osteoarthritis patients participated in the study.
      Sociodemographic and clinical data were collected and the Hospital Anxiety and
      Depression Scale and the Disability Index of the Health Assessment Questionnaire
      were applied. RESULTS: The prevalence of depressive symptoms was of 53.2% in
      rheumatoid arthritis and 28.3% in osteoarthritis (p = 0.005). The prevalence of
      anxiety symptoms was of 48.4% in rheumatoid arthritis and 50.0% in osteoarthritis
      (p = 0.859). The mean (and standard deviation) scores in the Disability Index of
      the Health Assessment Questionnaire were 1.4 (0.8) in rheumatoid arthritis and
      1.4 (0.6) in osteoarthritis (p = 0.864). Rheumatoid arthritis patients with
      depressive symptoms had lower education and higher disease activity and
      functional disability. CONCLUSION: Although these two rheumatic diseases are
      similar in terms of the pain and functional disability that they cause, a
      significantly higher prevalence of depressive symptoms was found in rheumatoid
      arthritis patients. This difference might be explained by the hypothesis of a
      neuroimmunobiological mechanism related to cytokines in inflammatory diseases,
      which has been considered as a candidate to the development of depressive
      symptoms.

PMID- 20694443
TI  - Effects of reversible inactivation of the dorsomedial hypothalamus on panic- and
      anxiety-related responses in rats.
AB  - The medial hypothalamus is part of a neurobiological substrate controlling
      defensive behavior. It has been shown that a hypothalamic nucleus, the
      dorsomedial hypothalamus (DMH), is involved in the regulation of escape, a
      defensive behavior related to panic attacks. The role played by the DMH in the
      organization of conditioned fear responses, however, is less clear. In the
      present study, we investigated the effects of reversible inactivation of the DMH
      with the GABA A agonist muscimol on inhibitory avoidance acquisition and escape
      expression by male Wistar rats (approximately 280 g in weight) tested in the
      elevated T-maze (ETM). In the ETM, inhibitory avoidance, a conditioned defensive
      response, has been associated with generalized anxiety disorder. Results showed
      that intra-DMH administration of the GABA A receptor agonist muscimol inhibited
      escape performance, suggesting an antipanic-like effect (P < 0.05), without
      changing inhibitory avoidance acquisition. Although a higher dose of muscimol
      (1.0 nmol/0.2 uL; N = 7) also altered locomotor activity in an open field when
      compared to control animals (0.2 uL saline; N = 13) (P < 0.05), the lower dose
      (0.5 nmol/0.2 uL; N = 12) of muscimol did not cause any motor impairment. These
      data corroborate previous evidence suggesting that the DMH is specifically
      involved in the modulation of escape. Dysfunction of this regulatory mechanism
      may be relevant in the genesis/maintenance of panic disorder.

PMID- 20694444
TI  - Effects of furrow irrigation on the growth, production, and water use efficiency
      of direct sowing rice.
AB  - Rice farming is the major crop production in Asia and is predicted to increase
      significantly in the near future in order to meet the demands for the increasing
      human population. Traditional irrigation methods used in rice farming often
      result in great water loss. New water-saving methods are urgently needed to
      reduce water consumption. Three field and pot experiments were conducted to
      evaluate the furrow irrigation (FI) system to improve water use efficiency (WUE)
      and production of direct sowing rice in southern China. Compared to the
      conventional irrigation (CI) system (continuous flooding irrigation), for every
      square hectometer of rice field, the FI system reduced water use by 3130 m3, or
      48.1%, and increased grain production by 13.9% for an early cultivar. For a late
      cultivar, the FI system reduced water use by 2655 m3, or 40.6%, and an increase
      of grain production by 12.1%. The improved WUE in the FI system is attributed to
      (1) a significant reduction of irrigation rate, seepage, evaporation, and
      evapotranspiration; (2) a significant reduction in the reduced materials, such as
      ferrous ion (Fe2+), and therefore an increase in the vitality of the root system,
      evident by the increases in the number of white roots by 32.62%, and decreases in
      the number of black roots by 20.04% and yellow roots by 12.58%; the use of the FI
      system may also reduce humidity of the rice field and enhance gas transport in
      the soil and light penetration, which led to reduced rice diseases and increased
      leaf vitality; and (3) increases in tiller and effective spikes by 11.53% and the
      weight per thousand grains by 1.0 g. These findings suggest that the shallow FI
      system is a promising means for rice farming in areas with increasing water
      shortages.

PMID- 20694445
TI  - Phosphorus leaching in an acid tropical soil "recapitalized" with phosphate rock
      and triple superphosphate.
AB  - With high rates of phosphorus applied to increase "capital P" as a stock for
      plant uptake over several years, the question of P leaching is inevitable. We
      conducted an intact soil column experiment in the field to evaluate P leached
      from soils treated with triple superphosphate (TSP) and Gafsa phosphate rock
      (GPR) at 300, 600, and 900 kg P ha-1 with and without integration of cattle
      manure. The lysimeters, made from PVC tubes of 30-cm length, were inserted into
      the soil up to the 25-cm depth. The tubes were fitted with a resin bag containing
      a mixture of cation and anion exchange resin (50:50) at the lower end of the tube
      inserted into the soil. The tubes, arranged in a completely randomized design,
      were sampled randomly at 10-week intervals for 12 months. Phosphorus extractable
      from the top- and subsoil at the end of experiment and leached P were determined.
      More P was leached out from TSP (threefold) compared to GPR, and the amount of P
      leached increased with increasing rates of P fertilizer applied. Application of
      manure intensified the amounts of P leached from TSP, particularly at the 6-month
      sampling time. There was hardly any substantial P leached from the soil treated
      with GPR. Thus, for effective and efficient long-term P fertilizer management
      strategies, choosing the right P fertilizer source and monitoring P losses
      through leaching has to be done for enhanced fertilizer use efficiency and thus
      reducing P pollution of ground waters.

PMID- 20694446
TI  - Effectiveness of the Tier 1 Program of Project P.A.T.H.S.: findings based on
      three years of program implementation.
AB  - The Tier 1 Program of the Project P.A.T.H.S. (Positive Adolescent Training
      through Holistic Social Programmes) is a positive youth development program
      implemented in school settings, utilizing a curricular-based approach. In the
      third year of the Full Implementation Phase, 19 experimental schools (n = 3,170
      students) and 24 control schools (n = 3,808 students) participated in a
      randomized group trial. Utilizing the six-wave longitudinal data, ANCOVA, and
      linear mixed models controlling for differences between the two groups in terms
      of Wave 1 pretest scores, personal variables, and random effects of schools, it
      was revealed that participants in the experimental schools showed significantly
      better development than did participants in the control schools at post-test
      (Wave 6) based on different indicators of positive youth development derived from
      the Chinese Positive Youth Development Scale and other measures. Students in the
      experimental schools also displayed a lower level of intention to engage in
      problem behavior and better school adjustment than did students in the control
      schools. Similarly, differences between experimental participants who perceived
      the program to be beneficial and control participants were found.

PMID- 20694447
TI  - Proposal of a holistic model to support local-level evidence-based practice.
AB  - In response to a central drive for evidence-based practice, there have been many
      research support schemes, setups, and other practices concentrating on
      facilitating access to external research, such as the Centre for Evidence Based
      Healthcare Aotearoa, the Cochrane Collaboration, and the York Centre for Reviews
      and Dissemination. Very little attention has been paid to supporting internal
      research in terms of local evidence and internal research capabilities. The whole
      evidence-based practice movement has alienated internal decision makers and,
      thus, very little progress has been made in the context of evidence informing
      local policy formation. Health and social policies are made centrally based on
      dubious claims and often evidence is sought after implementation. For example, on
      record, most health care practitioners appear to agree with the causal link
      between depression and mental illness (sometimes qualified with other social
      factors) with suicide; off the record, even some psychiatrists doubt that such a
      link is applicable to the population as a whole. Therefore, be it through
      misplaced loyalty or a lack of support for internal researchers/decision makers,
      local evidence informing local decision making may have been ignored in favour of
      external evidence. In this paper, we present a practical holistic model to
      support local evidence-based decision making. This approach is more relevant in
      light of a new approach to primary health care of "local knowledge" complementing
      external evidence. One possible outcome would be to network with other regional
      programmes around the world to share information and identify "best" practices,
      such as the "Stop Youth Suicide Campaign" (www.stopyouthsuicide.com).

PMID- 20694448
TI  - Ashy ears.
AB  - Alkaptonuria is a rare, autosomal-recessive disease of tyrosine degradation
      resulting from accumulation of homogentisic acid (HGA) within the body due to
      deficiency of the hepatic enzyme homogentisate 1,2-dioxygenase[1]. HGD is the
      gene encoding homogentisate 1,2-dioxygenase and is the only gene known to be
      associated with alkaptonuria. In this patient the disease also manifested itself
      with symmetric blue-gray discoloration on the helix cartilage of his ears. The
      initial diagnosis of alkaptonuria was made some 20 years earlier because of the
      appearance of low back pain and dark urine. HGA is responsible for the black
      color of urine and is deposited in the cartilage of the body, including ears.

PMID- 20694449
TI  - Liver abscess due to sewing needle perforation.
AB  - A 45-year-old female was admitted to the hospital with a 1-week history of right
      upper abdominal pain and nausea. Ultrasonography showed a thickened duodenum with
      infiltration. Subsequent gastroscopy did not reveal any abnormalities. CT scan
      showed a foreign body perforation at the duodenum and a liver abscess (Fig.
      1A,B). A diagnostic laparoscopy was performed. During the operation, the abscess
      was drained (Fig. 2A,B) and a sewing needle was removed (Fig. 3A,B). The patient
      claimed to have no recollection of swallowing the needle and made a quick
      recovery. Although rare, gastrointestinal perforations due to ingested foreign
      bodies most frequently occur at ileocecal, rectosigmoid, and duodenal regions[1].
      Sewing needle perforations into the liver have been reported in children, adults,
      and psychiatric cases. Symptoms can vary from mild gastric pain to signs of
      peritonitis[2]. "Wait and see" is recommended for asymptomatic patients with no
      complications. Symptomatic patients (e.g., liver abscess) need surgical
      intervention[1,2,3].

PMID- 20694450
TI  - Ureteritis cystica presenting with atrophic kidney: report of a case.
AB  - Ureteritis cystica is a rare proliferative condition that is found predominantly
      in the bladder, renal pelvis, and upper ureter. It may occlude the ureteral lumen
      and should be considered in the reasons for an atrophic kidney. A 65-year-old
      female with a 2-year history of right flank pain that increased in the last 2
      months was presented. Abdominal ultrasonography revealed right-sided atrophic
      kidney. Nephroureterectomy was performed. On the gross examination, along the
      ureter wall, there were numerous polyps, 0.5 cm in maximum diameter, protruding
      into the lumen. On the histopathological evaluation, ureteritis cystica and
      chronic pyelonephritis was detected. In conclusion, ureteritis cystica is a
      benign and indolent lesion that needs to be kept in mind among the causes of
      renal atrophy.

PMID- 20694451
TI  - Acute renal failure and severe hypertension from a page kidney post-transplant
      biopsy.
AB  - Page kidney refers to a clinical picture characterized by acute onset of
      hypertension due to external compression of the kidneys from hematoma, tumor,
      lymphocele, or urinoma. Hypertension is believed to result from renin-angiotensin
      aldosterone activation triggered by renal hypoperfusion and microvascular
      ischemia. Renal failure, in addition to hypertension, may occur in the setting of
      a single functional kidney or a diseased contralateral kidney. We report a case
      of a patient who had a transplant kidney biopsy complicated by a subcapsular
      perinephric hematoma. The patient presented with an acute increase in blood
      pressure and a rapid rise in serum creatinine following a transplant kidney
      routine biopsy. He underwent emergent evacuation of the perinephric hematoma,
      with consequent decrease of his blood pressure and return of serum creatinine
      back to his baseline level. Early recognition and rapid intervention are needed
      in order to correct hypertension and reverse acute renal failure in Page kidney
      occurring in renal transplant recipients.

PMID- 20694452
TI  - Heat shock proteins: cell protection through protein triage.
AB  - Heat shock proteins (HSPs) are chaperones that catalyze the proper folding of
      nascent proteins and the refolding of denatured proteins. The ubiquitin
      proteasome system is an error-checking system that directs improperly folded
      proteins for destruction. A coordinated interaction between the HSPs
      (renaturation) and the proteasome (degradation) must exist to assure protein
      quality control mechanisms. Although it still remains unknown how the decision of
      folding vs. degradation is taken, many pieces of evidence demonstrate that HSPs
      interact directly or indirectly with the proteasome, assuring quite selectively
      the proteasomal degradation of certain proteins under stress conditions. In this
      review, we will describe the different data that demonstrate a role for HSP90,
      HSP70, HSP27, and aB-crystallin in the partitioning of proteins to either one of
      these pathways, referred as protein triage.

PMID- 20694453
TI  - Publication of a special issue: resolution of acute inflammation and the role of
      lipid mediators.

PMID- 20694454
TI  - [Chronic urticaria. Prevalence, course, prognostic factors and impact].
AB  - Chronic urticaria (CU) is one of the most frequent diseases in the field of
      dermatology. Recent studies have shown a point prevalence between 0.5 and 1% in
      the total population with a predominance of females. In general, all age groups
      and all classes of the population can be affected. An incidence peak has been
      found in the third and fourth decades. According to the current guidelines, CU is
      characterized by the spontaneous occurrence of wheals and/or angioedema for more
      than 6 weeks. However, epidemiological studies have revealed that the majority of
      patients suffer for several months, or frequently years. Disease duration is
      likely to be longer in case of angioedema, a combination with physical urticaria,
      positivity in the autologous serum skin test (autoreactivity) and a high disease
      severity. Studies on the impairment of quality of life have been shown that many
      CU patients suffer as strong from their disease as patients with coronary artery
      disease. Apart from pure physical symptoms, patients experience restrictions in
      daily life activities and social life. In addition, sleep disturbances are common
      and CU patients frequently exhibit psychiatric comorbidities. To avoid
      frustration in care, it is important to perceive all different dimensions of CU
      that impact the patient's life and to take the patients and their disease
      seriously. The aim of therapy should be to obtain total symptom control.

PMID- 20694455
TI  - Cholesterol toxicity in pancreatic islets from LDL receptor-deficient mice.

PMID- 20694456
TI  - Bisphosphonate use and risk of post-operative fracture among patients undergoing
      a total knee replacement for knee osteoarthritis: a propensity score analysis.
AB  - SUMMARY: We have shown that patients with osteoarthritis are at increased risk of
      fracture after total knee replacement (TKR). We conducted a population-based
      cohort study to assess the effect of bisphosphonate use on their post-surgery
      fracture risk. Cox regression adjusted by propensity score suggested a 50-55%
      reduction in risk of fracture post-surgery. INTRODUCTION: Patients with
      osteoarthritis have a higher bone mass but similar or higher risk of fracture. We
      recently demonstrated that patients have an elevated fracture risk after TKR, but
      it is unknown if bisphosphonate therapy in this patient group would reduce
      fracture risk. We aimed to assess the effect of bisphosphonate prescription to
      patients undergoing a TKR, on their risk of fracture after surgery. METHODS: From
      the General Practice Research Database, all patients >= 40 years old, who
      received a TKR from 1986 to 2006 for knee osteoarthritis were eligible. We
      identified bisphosphonate use (BPU) as the main exposure. Propensity scores
      (equivalent to the estimated conditional probability of being treated given the
      individual's covariates) were calculated using logistic regression and used to
      reduce observed confounding. We fitted Cox models to study the effect of BPU on
      post-surgery fracture occurrence. Analyses were stratified by history of previous
      fracture: no fracture, osteoporotic fracture (hip, wrist, humerus, spine), and
      other fractures. RESULTS: The hazard ratio (HR) associated with BPU in non
      previously fractured patients was 0.50 (95% confidence interval, 0.37-0.68;
      propensity-adjusted model), and 0.48 (0.35-0.65; matched analysis). In subjects
      with osteoporotic and with other previous fracture, BPU was associated with a
      propensity-adjusted HR of 0.46 (0.30 to 0.71) and 0.47 (0.26-0.85), respectively,
      and with a propensity-matched HR of 0.45 (0.29 to 0.70) and 0.45 (0.25-0.82).
      CONCLUSION: Our results suggest that BPU in primary prevention could reduce post
      operative risk of fracture by 50% and by 55% in secondary prevention.

PMID- 20694457
TI  - Associations of physical activity duration, frequency, and load with volumetric
      BMD, geometry, and bone strength in young girls.
AB  - SUMMARY: More efficacious physical activity (PA) prescriptions for optimal bone
      development are needed. This study showed that PA duration, frequency, and load
      were all independently associated with bone parameters in young girls. Increased
      PA duration, frequency, and load are all important osteogenic stimuli that should
      be incorporated into future PA interventions. INTRODUCTION: This study evaluated
      the associations of physical activity (PA) duration, frequency, load, and their
      interaction (total PA score = duration * frequency * load) with volumetric bone
      mineral density, geometry, and indices of bone strength in young girls. METHODS:
      Four hundred sixty-five girls (aged 8-13 years) completed a past year physical
      activity questionnaire (PYPAQ) which inquires about the frequency (days per week)
      and duration (average minutes per session) of leisure-time PA and sports. Load
      (peak strain score) values were assigned to each activity based on ground
      reaction forces. Peripheral quantitative computed tomography was used to assess
      bone parameters at metaphyseal and diaphyseal sites of the femur and tibia of the
      non-dominant leg. RESULTS: Correlations across all skeletal sites between PA
      duration, frequency, load and periosteal circumference (PC), bone strength index
      (BSI), and strength-strain index (SSI) were significant (p <= 0.05), although low
      (0.10-0.17). A 2.7-3.7% greater PC across all skeletal sites was associated with
      a high compared to a low PYPAQ score. Also, a high PYPAQ score was associated
      with greater BSI (6.5-8.7%) at metaphyseal sites and SSI (7.5-8.1%) at diaphyseal
      sites of the femur and tibia. The effect of a low PYPAQ score on bone geometric
      parameters and strength was greater than a high PYPAQ score. CONCLUSIONS: PA
      duration, frequency, and load were all associated with bone geometry and
      strength, although their independent influences were modest and site specific.
      Low levels of PA may compromise bone development whereas high levels have only a
      small benefit over more average levels.

PMID- 20694458
TI  - The development of a rapid method for the isolation of four azaspiracids for use
      as reference materials for quantitative LC-MS-MS methods.
AB  - The azaspiracids are a family of lipophilic polyether marine biotoxins that have
      caused a number of human intoxication incidents in Europe since 1995 after
      consumption of contaminated shellfish (Mytilus edulis). Levels of azaspiracids in
      shellfish for human consumption are monitored in accordance with EU guidelines:
      only shellfish with less than 160 microg kg(-1) are deemed safe. The limited
      availability of commercially available standards for azaspiracids is a serious
      problem, because validated LC-MS methods are required for routine analysis of
      these toxins in shellfish tissues. The procedure described herein has been used
      for the separation and the isolation of four azaspiracid (AZA) toxins from
      shellfish, for use as LC-MS-MS reference materials. Five separation steps have
      been used to isolate azaspiracids 1, 2, 3, and 6. The purity of the toxins
      obtained has been confirmed by multiple mass spectrometric methods using
      authentic azaspiracid standards. The same techniques have been used for
      quantification of the toxins extracted. The isolation procedure involves several
      chromatographic purification techniques: solid-phase extraction (diol sorbent,
      90% mass reduction, and 95 +/- 1% toxin recovery); Sephadex size-exclusion
      chromatography (87% mass reduction and up to 95 +/- 2% toxin recovery), Toyopearl
      HW size-exclusion chromatography (90% mass reduction and up to 92.5 +/- 2.5%
      toxin recovery), and semi-preparative LC (78 +/- 3% toxin recovery). The
      procedure effectively separates the toxins from the sample matrix and furnishes
      azaspiracid toxins (AZA1, AZA2, AZA3 and AZA6) of sufficient purity with an
      average yield of 65% (n = 5). Triple-quadrupole mass spectrometry was used for
      qualitative and quantitative monitoring of the isolation efficiency after each
      stage of the process. High-resolution mass spectrometric evaluation of the toxic
      isolated material in both positive and negative modes suggests high purity.

PMID- 20694459
TI  - Appropriateness of treatment recommendations for PPI in hospital discharge
      letters.
AB  - PURPOSE: The reasons for the dramatic increase in proton pump inhibitors (PPI)
      prescriptions remain unclear and cannot be explained solely by increased
      morbidity, new indications or a decrease in alternative medication. Inappropriate
      use and discharge recommendations in hospitals are considered to be possible
      explanations. As the quality of PPI recommendations in hospital discharge letters
      in Germany has not been investigated to date, we have studied the appropriateness
      of these referrals. METHODS: Hospital discharge letters with recommendations for
      PPI medication from 35 primary care practices in the county of Mecklenburg
      Western Pomerania (MV; North-east Germany) were collected and analysed, and the
      appropriateness of the PPI indication was rated. RESULTS: No information
      justifying the recommendation for continuous PPI medication could be identified
      in 54.5% of the discharge letters; in 12.7%, the indication was uncertain, and in
      32.7%, we found an evidence-based indication for PPI medication. The most common
      indication for adequate PPI use was nonsteroidal anti-inflammatory drug
      prophylaxis in high-risk patients. CONCLUSIONS: Inadequate recommendations for
      PPIs in discharge letters are frequent. This may lead to a continuation of this
      therapy in primary care, thereby unnecessarily increasing polypharmacy and the
      risk of adverse events as well as burdening the public health budget. Hospitals
      should therefore critically review recommendations for PPI medication and the
      dosage thereof in their discharge letters and clearly document the reason for PPI
      use and the need for continuous prescription in primary care.

PMID- 20694461
TI  - Using CT perfusion during the early baseline period in aneurysmal subarachnoid
      hemorrhage to assess for development of vasospasm.
AB  - INTRODUCTION: The aim of this study is to evaluate computed tomography perfusion
      (CTP) during admission baseline period (days 0-3) in aneurysmal subarachnoid
      hemorrhage (A-SAH) for development of vasospasm. METHODS: Retrospective analysis
      was performed on A-SAH patients from Dec 2004 to Feb 2007 with CTP on days 0-3.
      Cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time
      (MTT) maps were analyzed for qualitative perfusion deficits. Quantitative
      analysis was performed using region-of-interest placement to obtain mean CTP
      values. Development of vasospasm was determined by a multistage hierarchical
      reference standard incorporating both imaging and clinical criteria. Student's t
      test and threshold analysis were performed. RESULTS: Seventy-five patients were
      included, 37% (28/75) were classified as vasospasm. Mean CTP values in vasospasm
      compared to no vasospasm groups were: CBF 31.90 ml/100 g/min vs. 39.88 ml/100
      g/min (P < 0.05), MTT 7.12 s vs. 5.03 s (P < 0.01), and CBV 1.86 ml/100 g vs.
      2.02 ml/100 g (P = 0.058). Fifteen patients had qualitative perfusion deficits
      with 73% (11/15) developed vasospasm. Optimal threshold for CBF is 24-25 mL/100
      g/min with 91% specificity and 50% sensitivity, MTT is 5.5 s with 70% specificity
      and 61% sensitivity and CBV is 1.7 mL/100 g with 89% specificity and 36%
      sensitivity. CONCLUSION: These initial results support our hypothesis that A-SAH
      patients who develop vasospasm may demonstrate early alterations in cerebral
      perfusion, with statistically significant CBF reduction and MTT prolongation.
      Overall, CTP has high specificity for development of vasospasm. Future clinical
      implications include using CTP during the baseline period for early
      identification of A-SAH patients at high risk for vasospasm to prompt robust
      preventative measures and treatment.

PMID- 20694462
TI  - Tanshinone biosynthesis in Salvia miltiorrhiza and production in plant tissue
      cultures.
AB  - Salvia miltiorrhiza Bunge (Lamiaceae) root, generally called Danshen, is an
      important herb in Chinese medicine widely used for treatment of cardiovascular
      diseases. Diterpenoid tanshinons are major bioactive constituents of Danshen with
      notable pharmacological activities and the potential as new drug candidates
      against some important human diseases. The importance of Danshen for traditional
      and modern medicines has motivated the research interest over two decades in the
      biosynthesis and biotechnological production of tanshinones. Although diterpenes
      in plants are presumably derived from the non-mevalonate (MVA) pathway,
      tanshinone biosynthesis in S. miltiorrhiza may also depend on the MVA pathway
      based on some key enzymes and genes detected in the early steps of these
      pathways. Plant tissue cultures are the major biotechnological processes for
      rapid production of tanshinones and other bioactive compounds in the herb.
      Various in vitro cultures of S. miltiorrhiza have been established, including
      cell suspension, adventitious root, and hairy root cultures, which can accumulate
      the major tanshinones as in the plant roots. Tanshinone production in cell and
      hairy root cultures has been dramatically enhanced with various strategies,
      including medium optimization, elicitor stimulation, and nutrient feeding
      operations. This review will summarize the above developments and also provide
      our views on future trends.

PMID- 20694460
TI  - The potential of cytokines as safety biomarkers for drug-induced liver injury.
AB  - Drug-induced liver injury (DILI) is an event that has a detrimental impact on
      drug development and patient safety; therefore the identification of novel
      biomarkers that are both sensitive and specific to the liver would have great
      benefit. Inflammation is known to be associated with human cases of DILI, and
      given the role of cytokines in modulating the inflammatory response, changes in
      cytokine expression patterns certainly show promise as potential biomarkers of
      DILI. Cytokines are interesting candidates for novel biomarkers as they are
      relatively accessible (by blood sampling) and accurately quantifiable. In
      particular, recent interest has developed in mechanism-specific, rather than
      tissue-specific, biomarkers. However, without fully understanding the role of
      inflammation in DILI and the role of cytokines in modulating the inflammatory
      response, cytokines may be limited in their use, being either diagnostic of the
      type of injury that has occurred and/or prognostic of outcome (recovery from
      DILI, cirrhosis, acute liver failure). Intracellular components released by
      damaged hepatocytes, although inaccessible and currently difficult to quantify,
      may be better biomarkers for the prognosis of severity of injury. In both cases
      there is a pressing need for the development and validation of assays sensitive
      enough and with a sufficient dynamic range to detect changes upon drug treatment.
      Although promising candidates are appearing in the literature, much remains to be
      done to understand the role of inflammation in DILI and the role that a given
      cytokine has in the inflammatory cascade associated with DILI before cytokines
      are viewed as biomarkers for DILI.

PMID- 20694463
TI  - 18F-fluorodeoxyglucose positron emission tomography and computed tomography in
      anaplastic thyroid cancer.
AB  - PURPOSE: Our aim was to evaluate in anaplastic thyroid carcinoma (ATC) patients
      the value of 18F-FDG PET/CT compared with total body computed tomography (CT)
      using intravenous contrast material for initial staging, prognostic assessment,
      therapeutic monitoring and follow-up. METHODS: Twenty consecutive ATC patients
      underwent PET/CT for initial staging. PET/CT was performed again during follow
      up. The gold standard was progression on imaging follow-up (CT or PET/CT) or
      confirmation with another imaging modality. RESULTS: A total of 265 lesions in 63
      organs were depicted in 18 patients. Thirty-five per cent of involved organs were
      demonstrated only with PET/CT and one involved organ only with CT. In three
      patients, the extent of disease was significantly changed with PET/CT that
      demonstrated unknown metastases. Initial treatment modalities were modified by
      PET/CT findings in 25% of cases. The volume of FDG uptake (>=300 ml) and the
      intensity of FDG uptake (SUVmax>=18) were significant prognostic factors for
      survival. PET/CT permitted an earlier assessment of tumour response to treatment
      than CT in 4 of the 11 patients in whom both examinations were performed. After
      treatment with combined radiotherapy and chemotherapy, only the two patients with
      a negative control PET/CT had a confirmed complete remission at 14 and 38 months;
      all eight patients who had persistent FDG uptake during treatment had a clinical
      recurrence and died. CONCLUSION: FDG PET/CT appears to be the reference imaging
      modality for ATC at initial staging and seems promising in the early evaluation
      of treatment response and follow-up.

PMID- 20694464
TI  - Cone over guide wire technique for difficult IVC filter retrieval.

PMID- 20694465
TI  - Transcatheter arterial embolization for spontaneous rupture of the omental
      artery.
AB  - We encountered a rare case of spontaneous rupture of the omental artery. A 25
      year-old man without any episode of abdominal trauma or bleeding disorders came
      to the emergency unit with left upper abdominal pain. Hematoma with extravasation
      of the greater omentum and a hemoperitoneum was confirmed on abdominal contrast
      enhanced computed tomography. Bleeding from the omental artery was suspected
      based on these findings. Transcatheter arterial embolization was successfully
      performed after extravasation of the omental artery, which arises from the left
      gastroepiploic artery, was confirmed on arteriography. Partial ometectomy was
      performed 10 days after transcatheter arterial embolization, revealing that the
      hematoma measured 10 cm in diameter in the greater omentum. Pathological
      examination showed rupture of the branch of an omental artery without abnormal
      findings, such as an aneurysm or neoplasm. Thus, we diagnosed him with
      spontaneous rupture of the omental artery. The patient recovered and was
      discharged from the hospital 10 days after the surgery, with a favorable
      postoperative course.

PMID- 20694466
TI  - Recanalization of dialysis catheter-related subclavian vein occlusion using a re
      entry device: report of two patients.

PMID- 20694467
TI  - Staff radiation doses in a real-time display inside the angiography room.
AB  - METHODS: The evaluation of a new occupational Dose Aware System (DAS) showing
      staff radiation doses in real time has been carried out in several angiography
      rooms in our hospital. The system uses electronic solid-state detectors with high
      capacity memory storage. Every second, it archives the dose and dose rate
      measured and is wirelessly linked to a base-station screen mounted close to the
      diagnostic monitors. An easy transfer of the values to a data sheet permits
      further analysis of the scatter dose profile measured during the procedure,
      compares it with patient doses, and seeks to find the most effective actions to
      reduce operator exposure to radiation. RESULTS: The cumulative occupational doses
      measured per procedure (shoulder-over lead apron) ranged from 0.6 to 350 MUSv
      when the ceiling-suspended screen was used, and DSA (Digital Subtraction
      Acquisition) runs were acquired while the personnel left the angiography room.
      When the suspended screen was not used and radiologists remained inside the
      angiography room during DSA acquisitions, the dose rates registered at the
      operator's position reached up to 1-5 mSv/h during fluoroscopy and 12-235 mSv/h
      during DSA acquisitions. In such case, the cumulative scatter dose could be more
      than 3 mSv per procedure. CONCLUSION: Real-time display of doses to staff members
      warns interventionists whenever the scatter dose rates are too high or the
      radiation protection tools are not being properly used, providing an opportunity
      to improve personal protection accordingly.

PMID- 20694468
TI  - Novel image-guided management of a uterine arteriovenous malformation.
AB  - The investigators present a novel image-guided embolization, not previously
      described, of a uterine arteriovenous malformation (AVM) resistant to
      endovascular management. The uterus was exposed surgically, and Histoacryl
      (Braun, Fulda, Germany) was injected directly into the nidus using ultrasound
      guidance and fluoroscopy. The patient had a successful full-term pregnancy after
      this procedure. This technique may be a useful alternative management strategy in
      patients with uterine AVM who fail traditional endovascular embolization and who
      still desire fertility.

PMID- 20694469
TI  - Sickle-cell disease and malaria: evaluation of seasonal intermittent preventive
      treatment with sulfadoxine-pyrimethamine in Senegalese patients-a randomized
      placebo-controlled trial.
AB  - Sickle-cell disease (SCD) patients are at high risk of developing malaria which
      is a major contributor to morbidity and mortality in this disease. In Senegal,
      malaria transmission is high during rainy season, between July and October, and
      it was noted that sickle-cell crisis are frequent during this period. Then we
      carried out a double-blind randomized controlled trial to compare the impact of
      monthly sulfadoxine-pyrimethamine (SP) during the high-transmission season versus
      placebo on malaria incidence and morbidity of sickle-cell anemia. Sixty (60) SCD
      patients were randomized either to receive three intermittent preventive
      treatment (ITP) with SP or placebo using the random permutation table with nine
      elements. The drug was administrated as follows: sulfadoxine 25 mg/kg and
      pyrimethamine 1.25 mg/kg and this treatment was given once during the following
      months: September, October, and November. Overall four episodes of malaria
      disease were diagnosed, all these cases in the placebo arm. Thus, overall
      prevalence was 6.6% and there was no other case of malaria in the SP arm during
      the study period. Parasitological diagnosis confirmed the presence of Plasmodium
      falciparum in all four cases. No patient death was encountered during the study.
      SP treatment was well tolerated as only one patient (1.6%) in the SP arm reported
      pruritus. A significant reduction of patients' complaints (p = 002) and blood
      requirements (p = 0.001) was noted in the SP group; whereas, no impact was
      observed on vaso-occlusive crisis and hospitalization occurrence. Malaria
      prophylaxis by monthly intake of SP during the transmission period of the
      parasite reduced the prevalence of malaria and was safe in SCD patients leaving
      in malaria endemic area.

PMID- 20694470
TI  - Diffusion-weighted MRI for detecting liver metastases: importance of the b-value.

PMID- 20694471
TI  - Liver iron concentration quantification by MRI: are recommended protocols
      accurate enough for clinical practice?
AB  - OBJECTIVE: To assess the accuracy of quantification of liver iron concentration
      (LIC) by MRI using the Rennes University (URennes) algorithm. METHODS: In the
      overall study period 1999-2006 the LIC in 171 patients was calculated with the
      URennes model and the results were compared with LIC measured by liver biopsy.
      RESULTS: The biopsy showed that 107 patients had no overload, 38 moderate
      overload and 26 high overload. The correlation between MRI and biopsy was r=0.86.
      MRI correctly classified 105 patients according to the various levels of LIC.
      Diagnostic accuracy was 61.4%, with a tendency to overestimate overload: 43% of
      patients with no overload were diagnosed as having overload, and 44.7% of
      patients with moderate overload were diagnosed as having high overload. The
      sensitivity of the URennes method for high overload was 92.3%, and the
      specificity for the absence of overload was 57.0%. MRI values greater than 170
      MUmol Fe/g revealed a positive predictive value (PPV) for haemochromatosis of
      100% (n=18); concentrations below 60 MUmol Fe/g had a negative predictive value
      (NPV) of 100% for haemochromatosis (n=101). The diagnosis in 44 patients with
      intermediate values remained uncertain. CONCLUSIONS: The assessment of LIC with
      the URennes method was useful in 74.3% of the patients to rule out or to diagnose
      high iron overload. The method has a tendency to overestimate overload, which
      limits its diagnostic performance.

PMID- 20694472
TI  - Psychosocial aspects of follow-up of children operated for intermediate anorectal
      malformations.
AB  - PURPOSE: To determine the degree of stress in parents of children operated for
      intermediate anorectal malformations, and their quality of life (QOL) at follow
      up. METHODS: Forty-two of the 166 children who had undergone a sacroperineal
      pullthrough operation for an intermediate type of anorectal malformation, between
      1996 and 2005, in the department of paediatric surgery at Christian Medical
      College, Vellore, responded to follow-up. The psychosocial well-being of the
      parents and the QOL of the children were assessed by an independent observer.
      RESULTS: The main factor which aggravated the stress and caused dissatisfaction
      with the final outcome was fecal soiling. Mothers bore the brunt of the care of
      these children, with some help from the fathers and grandparents. The QOL was
      also significantly affected by soiling, and improvement in soiling resulted in a
      dramatic improvement in the QOL. CONCLUSION: Managing fecal soiling aggressively
      in the child with anorectal malformation, and providing social support to the
      family, are crucial for achieving a better QOL in these children and their
      families.

PMID- 20694473
TI  - Spherical aberration and higher order aberrations with Balafilcon A (PureVision)
      and Comfilcon A (Biofinity).
AB  - BACKGROUND: Advances in the optical design of soft contact lenses have seen
      certain manufacturers incorporate aspheric optics into soft lenses in an attempt
      to reduce spherical aberration, to provide superior visual performance. The aim
      of this study is to determine the on-eye differences in spherical aberration and
      higher order aberrations (HOA) between the Bausch and Lomb PureVision (Balafilcon
      A) and the CooperVision Biofinity (Comfilcon A). METHODS: Twenty subjects were
      recruited in a prospective, randomized, unilateral study. The right eye was
      dilated and HOA measured with the NIDEK OPD-Scan. Each eye was fitted randomly
      with a -3.00D PureVision and a -3.00D Biofinity, and HOA were measured with
      lenses in situ across a 6 mm pupil. Paired t-tests were performed to determine
      HOA differences with the lenses in situ compared to baseline. RESULTS:
      Aberrometry was successfully performed on all subjects. Statistical analysis
      indicated no changes in spherical aberration, but changes in other HOA. With the
      PureVision, there were increases in Zernike terms Z (3) (1) (from 0.01 MUm to 
      0.11 MUm), Z (4) (-2) (from 0.01 MUm to 0.13 MUm) and Z (5) (-1) (from -0.01 MUm
      to 0.03 MUm). With the Biofinity there was an increase in Zernike term Z (3) (3)
      (from 0.00 MUm to 0.09 MUm). CONCLUSIONS: No statistically significant changes
      occurred in spherical aberration. The PureVision caused statistically significant
      increases in Z (3) (1) , Z (4) (-2) and Z (5) (-1) , and the Biofinity caused an
      increase in Z (3) (3) . Clinically significant changes (>0.1 MUm) occurred with
      terms Z (3) (1) and Z (4) (-2) with the PureVision only.

PMID- 20694474
TI  - Effects of sweep VEP parameters on visual acuity and contrast thresholds in
      children and adults.
AB  - BACKGROUND: There are many parameters that may impact the thresholds obtained
      with sweep visually evoked potentials (sVEP), yet a number of these parameters
      have not been systematically studied, and there is no recognised standard for
      sVEP recording. In this study, the effects of electrode placement, temporal
      frequency, sweep direction, presence of a fixation target, stimulus area, and
      sweep duration on visual acuity (VA) and contrast thresholds of the sVEP were
      investigated. Additionally, the effect of these parameters on the number of
      viable threshold readings obtained from five active electrodes was investigated.
      METHODS: Participants were six children (aged 6-8 years) and six adults (aged 17
      30 years) with normal vision. Binocular sVEP VA and contrast thresholds were
      measured for two electrode placements (ISCEV and PowerDiva) of five active
      electrodes, three temporal frequencies (6, 7.5, and 10 Hz), two sweep directions
      (low to high and high to low), presence or absence of a fixation target, three
      stimulus areas, and three sweep durations. RESULTS: There were differences
      between adults and children with respect to visual acuity, the adults having
      better VA than the children (p = 0.033 in experiment 2). Overall, there were more
      viable readings at 7.5 Hz than at either 10 or 6 Hz (p = 0.0014 for VA and 0.001
      for contrast thresholds). The adults performed better (in terms of viable
      readings) with the fixation target than without it (p = 0.04). The smallest
      stimulus size used gave rise to fewer viable readings in both adults and children
      (p = 0.022 for VA and 0.0001 for contrast thresholds). The other parameters
      (electrode placement, sweep direction and sweep duration) did not give rise to
      significant differences. CONCLUSIONS: A temporal frequency of 7.5 Hz, a stimulus
      area of 4 degrees  or larger for VA and 10 degrees  or larger for contrast
      thresholds, and the use of a fixation target gave more viable readings, and may
      be indicated for future application. Consideration of the number of viable
      readings showed more differences between parameters than the actual thresholds,
      and it is suggested that more readings presumably would yield more reliable
      threshold measurements.

PMID- 20694475
TI  - Totally endoscopic lateral parathyroidectomy: prospective evaluation of 200
      patients. ESES 2010 Vienna presentation.
AB  - PURPOSE: Several new minimally invasive techniques (mini-open, video-assisted,
      and endoscopic procedures) for parathyroidectomy have been described. However,
      totally endoscopic lateral approach parathyroidectomy (Henry technique) is not
      routinely performed. METHODS: This is a prospective study of 200 consecutive
      patients that underwent totally endoscopic lateral parathyroidectomy. RESULTS:
      Two hundred of 387 patients (52%) with primary hyperparathyroidism were included.
      Fifty-six patients (28%) were converted to open parathyroidectomy. Causes for
      conversion were lack of intraoperative localization (11%), difficult dissection
      (10%), bleeding (4%), failure of normalization of IOPTH results (2%), and other
      causes (1%). Gland localization (areas 1 to 2 versus area 3) and CaPTHus score
      (<3 versus >=3) were not associated with the risk of conversion. Mean
      postoperative follow-up was 13 months, and 196 patients (98%) were cured.
      CONCLUSIONS: Totally endoscopic lateral approach can be proposed in more than
      half of the patients with good immediate results. Conversion rate remains
      important and may explain low acceptance rate of this technique.

PMID- 20694476
TI  - Growth/differentiation factor-11: an evolutionary conserved growth factor in
      vertebrates.
AB  - Growth and differentiation factor-11 (GDF-11) is a member of the transforming
      growth factor-beta superfamily and is thought to be derived together with
      myostatin (known also as GDF-8) from an ancestral gene. In the present study, we
      report the isolation and characterization of GDF-11 homolog from a marine
      teleost, the gilthead sea bream Sparus aurata, and show that this growth factor
      is highly conserved throughout vertebrates. Using bioinformatics, we identified
      GDF-11 in Tetraodon, Takifugu, medaka, and stickleback and found that they are
      highly conserved at the amino acid sequence as well as gene organization.
      Moreover, we found conservation of syntenic relationships among vertebrates in
      the GDF-11 locus. Transcripts for GDF-11 can be found in eggs and early embryos,
      albeit at low levels, while in post-hatching larvae expression levels are high
      and decreases as development progresses, suggesting that GDF-11 might have a role
      during early development of fish as found in tetrapods and zebrafish. Finally,
      GDF-11 is expressed in various tissues in the adult fish including muscle, brain,
      and eye.

PMID- 20694477
TI  - TTF1 expression in normal lung neuroendocrine cells and related tumors:
      immunohistochemical study comparing two different monoclonal antibodies.
AB  - Thyroid transcription factor-1 (TTF1) regulates lung morphogenesis and
      differentiation, and its immunohistochemical expression is used for identifying
      lung neoplasms. The 8G7G3/1 antibody has been used in previous studies, but a
      different and more sensitive anti-TTF1 antibody, named SPT24, has become
      commercially available. Since the immunohistochemical expression of TTF1 in
      normal lung neuroendocrine (NE) cells has not been previously investigated and
      its utility in the diagnosis of lung NE tumors is a controversial issue, we
      studied the TTF1 expression in normal adult and fetal lungs, in 83 pulmonary NE
      neoplasms, in 131 non-lung NE tumors and in 36 metastases from these neoplasms
      using these two antibodies. A TTF1 immunoreactivity was demonstrated in normal
      fetal and adult NE cells when using the SPT24 clone. Conversely, using the
      8G7G3/1 antibody, only rare fetal neuroendocrine cells were TTF1 positive while
      adult NE cells were negative. The SPT24 clone identified TTF1 expression in more
      carcinoids, most of them peripherally located, and poorly differentiated NE
      carcinomas than the 8G7G3/1 clone. Non-pulmonary well-differentiated NE tumors
      were negative for both antibodies. Among the 45 non-pulmonary poorly
      differentiated NE carcinomas 11% were positive for 8G7G3/1 and 18% for SPT24.
      TTF1 expression in metastases perfectly reflected that detected in the related
      primary tumors. Our results indicate that the SPT24 antibody is more sensitive
      than the 8G7G3/1 clone for labeling lung carcinoids and it appears particularly
      useful in detecting peripheral neoplasms. In addition, the expression of TTF1 in
      normal NE cells suggests a possible role for the transcription factor in their
      development and differentiation.

PMID- 20694478
TI  - Spermatogenic cyst and organ culture in Drosophila pseudoobscura.
AB  - Spermatogenesis is a complex series of processes that involves (1) the
      maintenance of a renewable pool of diploid stem cells within a niche, (2) the
      mitotic expansion of a subpopulation of stem cells committed to the spermatogenic
      pathway, and (3) the differentiation of diploid cells into highly specialized,
      haploid spermatozoa through meiotic and post-meiotic cellular transformations.
      Drosophila melanogaster is a desirable model for studying spermatogenesis, as
      similarities exist between mammalian and fly spermatogenesis. Like mammals, flies
      maintain a spermatogenic stem cell niche; the steps involved in mammalian
      spermatogenesis are mimicked in flies, with the main difference being that fly
      sperm develop within cysts rather than an epithelial cell layer. Here, we report
      a reliable robust system for culturing whole testes and individual spermatogenic
      cysts obtained from mid- to late-pupal stages of Drosophila pseudoobscura. D.
      pseudoobscura testes can be easily distinguished in later pupal stages because of
      their intense red pigmentation and are easily handled because of their simple
      ellipsoidal morphology. Cultured cysts are comparable in length to cysts obtained
      from adult flies, and motility is consistently achieved in vitro. This system not
      only offers a method for dissecting the mechanisms involved in meiotic and post
      meiotic cellular transformations, but also can be used for the study of signaling
      during spermatogenesis.

PMID- 20694479
TI  - Systematic review of randomized controlled trial quality in pediatric kidney
      transplantation.
AB  - Limited pediatric-specific research can lead to sub-standard evidence for
      clinical decision making in children. We sought to systematically evaluate the
      methodological quality and the reporting standards of randomized controlled
      trials (RCTs) of transplantation trials in children. We included RCTs of kidney
      transplant recipients that had enrolled at least one child (aged 17 years or
      less) and that were reported in English language, peer reviewed journals from
      2000 onward in the Cochrane Renal Group's specialized register. Trial reports
      were assessed against the 22 item checklist of the CONsolidated Standards Of
      Reporting Trials (CONSORT) statement. Twenty-seven RCTs were included. The
      reporting of the essential components of the methods, results and discussion
      domains was unsatisfactory. Mean CONSORT criteria score for the pediatric trials
      was 67% and 66% for trials including both adults and children (p value for the
      difference = 1.00). Trial reporting quality in pediatric transplantation trials
      is not different from trials involving adults. It is evident that the reporting
      standards of RCTs in both adult and pediatric transplantation require major
      improvements. This work bench-marks current standards for future quality
      improvement.

PMID- 20694480
TI  - Duodenum-preserving versus pylorus-preserving pancreatic head resection for
      benign and premalignant lesions.
AB  - BACKGROUND/PURPOSE: Pylorus-preserving pancreaticoduodenectomy (PPPD) is the
      treatment of choice for benign or premalignant pancreatic head lesions. Duodenum
      preserving pancreatic head resection (DPPHR) has been reported in only 132
      patients. This study aimed to compare the long-term results of DPPHR and PPPD.
      METHODS: Patients who underwent DPPHR or PPPD for benign or borderline disease
      between 1991 and 2008 were followed up until December 2009 or their death.
      Endocrine and exocrine pancreatic functions were evaluated at their last follow
      up. RESULTS: Twenty-seven patients underwent DPPHR (Group 1) and 37 PPPD (Group
      2). They were followed for a mean of 100 and 135 months, respectively. Group 1
      had a higher complication rate (81.5 vs. 40.5%) and pancreatic fistula rate (40.1
      vs. 18.9%). Hospital mortality was 0 and 2.7%, respectively. Two patients died
      3.3 and 97 months after DPPHR. Significantly more Group 2 patients needed medical
      treatment for benign cholangitis (P < 0.0001). Insulin-dependent diabetes
      mellitus was observed in six Group 1 and 15 Group 2 patients (P = 0.077). Ten
      Group 1 and 21 Group 2 patients are taking pancreatic enzymes (P = 0.003).
      CONCLUSIONS: DPPHR for benign or premalignant lesions is a difficult procedure
      with a higher complication rate than PPPD, but was without mortality. Preserving
      the entire duodenum and a normal biliary tree allows better long-term results.

PMID- 20694481
TI  - Remifentanil increases the incidence of mesenteric traction syndrome: preliminary
      randomized controlled trial.
AB  - PURPOSE: The use of remifentanil is often associated with the observation of
      mesenteric traction syndrome (MTS) soon after manipulation of the intestine
      during abdominal surgery. MTS symptoms include facial flushing, hypotension, and
      tachycardia. In the study reported here, we prospectively investigated the
      effects of remifentanil on the incidence of MTS in abdominal surgery. METHODS:
      One hundred patients scheduled for abdominal surgery were randomly assigned to
      two groups. In one group (n = 50), fentanyl alone was used as intravenous
      analgesic (control, group C); in the second group (n = 50), both fentanyl and
      remifentanil were used (remifentanil group, group R). In all patients, anesthesia
      was induced with propofol and rocuronium and then maintained with sevoflurane
      inhalation. Remifentanil was continuously infused for patients in group R as an
      analgesic. Plasma concentration of 6-keto-PGF(1alpha) was measured before surgery
      and 20 min after the skin incision was made in six patients of group R and seven
      patients of group C. RESULTS: MTS occurred in 20 cases in group R (40.0%), but in
      only five cases in group C (10.0%). In both groups, the incidence of MTS was
      higher in laparotomy than in laparoscopic surgery. The plasma concentration of 6
      keto-PGF(1alpha) was low in both groups before surgery and was elevated 20 min
      after skin incision in both groups in patients in whom MTS appeared. CONCLUSIONS:
      The results of this study suggest that the use of remifentanil in laparotomy
      facilitates MTS.

PMID- 20694482
TI  - National survey to assess the content and availability of difficult-airway carts
      in critical-care units in the United States.
AB  - We have surveyed the availability of equipment, content of difficult-airway carts
      (DAC), and training in the use of such equipment in intensive-care units (ICU).
      We devised a set of proposals regarding what constitutes the ideal DAC. We
      surveyed 300 ICU in the United States. The survey was conducted to inquire about
      the presence and content of a DAC. Only 70% of respondents had a DAC in their
      unit. 82% of units surveyed checked the contents of the cart daily. 80% of
      directors were aware of its location. 80% of units had an attached list of
      contents and 51% had an attached algorithm for management of a difficult airway.
      LMA was present in 80% followed by 35 and 30% for Combitube and pre-assembled
      needle cricothyroidotomy set. Under non-invasive airway devices, video
      laryngoscope with 48% was ahead of fibreoptic bronchoscope (38%) and lighted
      stylet (15%). 80% of units had a CO2-detection device immediately available.
      Limited data are available on the impact of DAC in airway management in the ICU.
      It is strongly recommended that a DAC be present. What constitutes the ideal
      contents of a DAC is open to questions. We hope discussion will lead to consensus
      of what should or should not be included on the cart.

PMID- 20694483
TI  - Postoperative blindness associated with posterior reversible encephalopathy
      syndrome: a case report.
AB  - We report the case of a 46-year-old woman presenting with postoperative bilateral
      cerebral visual loss that was initially misinterpreted as an irreversible
      ischemic event. Magnetic resonance imaging of the brain showed high signal
      intensity on T2-weighted and fluid-attenuated inversion recovery images and
      normal signal intensity on diffusion-weighted images of the posterior lobe, which
      mostly disappeared with the improvement of clinical symptoms. Subsequent
      diagnosis revealed posterior reversible encephalopathy syndrome (PRES).
      Recognition of PRES as the correct diagnosis led to the appropriate management
      strategy and the recovery of normal vision. Differentiation from acute cerebral
      ischemia is important in order to prevent permanent vision loss due to delay in
      initiating prompt and vigorous treatment of exacerbating factors, such as
      intermittent hypertension. We believe that it is important for anesthesiologists
      and critical care physicians to accurately diagnose PRES in view of the key
      differences in the management of similarly presenting conditions.

PMID- 20694484
TI  - Extensive venous malformation: an alternative diagnosis to Klippel-Trenaunay
      syndrome.

PMID- 20694485
TI  - Parker Flex-Tip Tube((r)) facilitates intubation when the Pentax-AWS((r)) fails
      to reach the larynx.

PMID- 20694486
TI  - Confirmation rate of blinded (99m)Tc-SPECT compared to neurochemical dementia
      biomarkers in CSF in patients with Alzheimer disease.
AB  - In Alzheimer disease, CSF biomarkers and nuclear imaging are of particular
      interest. Many studies investigated only one technique, limiting comparison.
      Here, in 76 patients blinded 99mTc-SPECT was compared to CSF. Sensitivity of CSF
      was 92%; and 51% for SPECT. Specificity favored SPECT (90 vs. 80%). Both
      techniques showed no coherence (p = 0.17-0.47). Our results confirm that CSF
      biomarkers show higher sensitivity. SPECT has higher specificity and can also be
      used for other dementias without established CSF biomarkers.

PMID- 20694487
TI  - Behavioral sensitization to nicotine in female and male rats.
AB  - Behavioral sensitization to nicotine has been studied in both male and female
      rats, but studies up to now have been difficult to compare due to different
      experimental conditions. Including both sexes in scientific research is of great
      importance since clinical data indicate gender differences both in response to
      nicotine and in ability for smoking cessation. The aim of the present study was
      to compare behavioral sensitization and body-weight gain to two chronic doses of
      nicotine in female and male Wistar rats housed in unisex conditions. The rats
      received daily subcutaneous injections of vehicle or nicotine (0.2 or 0.4 mg/kg,
      free base) and locomotor activity was measured at days 1, 7, 14, 21, 28 and 37
      after administration of vehicle or nicotine (0.4 mg/kg). On day 45, all rats
      received an injection of nicotine. Body weights were monitored throughout the
      experiment. All rats receiving nicotine developed a sensitized response to the
      locomotor stimulatory effects of the drug. Male and female rats displayed a
      similar effect on horizontal and rearing activity after treatment with nicotine.
      Acute nicotine treatment induced a depressed rearing activity in male, but not
      female, rats; however, after chronic treatment the rats displayed a sensitized
      response. Furthermore, females treated with nicotine gained less weight compared
      to controls, while no such effect was seen in males. In conclusion, the present
      study does not support findings suggesting sex differences in development of
      behavioral sensitization to nicotine, while it demonstrates differences in
      nicotine-induced effects on weight gain in female and male rats.

PMID- 20694488
TI  - Further evidence that methylenetetrahydrofolate reductase A1298C polymorphism is
      a risk factor for schizophrenia.
AB  - Previous work suggests that the methylenetetrahydrofolate reductase gene (MTHFR)
      functional polymorphism A1298C may be a risk factor for schizophrenia. In this
      study, the genetic association between the MTHFR A1298C polymorphism and
      schizophrenia was investigated in 379 patients with schizophrenia and 380 age-
      and sex-matched controls subjects. The results showed an association between the
      1298C allele and the disorder (OR 1.39, 95% confidence interval 1.08-1.79). This
      provides further evidence that the MTHFR A1298C polymorphism may play a role in
      conferring risk for schizophrenia in the Chinese Han population.

PMID- 20694489
TI  - Serum concentrations of carboxylated osteocalcin are increased and associated
      with several components of the polycystic ovarian syndrome.
AB  - Intriguing studies suggest that osteocalcin (OC) and its carboxylated
      (Gla)/uncarboxylated form are involved in the regulation of insulin secretion and
      action. Additionally, advanced glycated end products (AGEs) directly regulate the
      secretion of these osteoblast-derived molecules. In polycystic ovarian syndrome
      (PCOS), among the pathophysiological aberrations, deregulation of insulin
      secretion and action as well as elevated AGEs levels have been demonstrated. In
      this study, we evaluated the serum levels of osteocalcin and Gla osteocalcin and
      their possible associations with metabolic, hormonal, and ultrasonographic
      components of PSOS: 97 women were studied, 50 PCOS patients and 47 controls,
      matched for age and body mass index (BMI). In each subject, the levels of bone
      metabolism markers have been evaluated, and metabolic and hormonal profiles as
      well as ovarian ultrasound were carried out. Osteocalcin (4.30 +/- 1.74 vs. 6.20
      +/- 1.78 ng/ml, P < 0.0005) values were significantly lower, whereas Gla
      osteocalcin (37.93 +/- 6.87 vs. 9.64 +/- 8.21 ng/ml, P < 0.0005) and receptor
      activator for nuclear factor-kappaB ligand (0.54 +/- 0.26 vs. 0.16 +/- 0.15
      pmol/l, P < 0.0005) values were significantly higher in PCOS subjects compared to
      the control group, independently of obesity. A significant association was
      disclosed between osteocalcin and Gla osteocalcin with androgens, insulin
      resistance, AGEs, and ovarian morphology. Receiver operating curve analysis
      revealed that Gla osteocalcin [AUC, 0.975 (95% CI, 0.93-1.00)] as well as AGEs
      are significant prognostic factors of PCOS [AUC, 0.986 (95% CI, 0.97-1.00)].
      Lower osteocalcin and elevated serum levels of its carboxylated form are
      displayed in PCOS subjects and are associated with several PCOS components. These
      findings suggest a potential interaction between bone-derived markers and the
      metabolic/hormonal abnormalities observed in PCOS. However, the
      pathophysiological mechanisms and moreover the possible clinical implications
      require further investigation.

PMID- 20694490
TI  - Boronated phosphonium salts containing arylboronic acid, closo-carborane, or nido
      carborane: synthesis, X-ray diffraction, in vitro cytotoxicity, and cellular
      uptake.
AB  - The preparation of boronated triaryl and tetraaryl phosphonium salts of the type
      [PPh(3)CH(2)R]Br [R is 4-boronophenyl (1), 4-(4,4,5,5-tetramethyl-1,3,2
      dioxaborolan-yl)phenyl (2), 3-boronophenyl (3), 3-(4,4,5,5-tetramethyl-1,3,2
      dioxaborolan-yl)phenyl (4), 2-boronophenyl (5), 2-(4,4,5,5-tetramethyl-1,3,2
      dioxaborolan-yl)phenyl (6), and closo-1,2-carboran-1-yl (7)] is described. These
      compounds were prepared by the reaction of triphenylphosphine with benzylic
      bromides or 1-bromomethyl-closo-1,2-carborane in acetonitrile solution at 85 
      degrees C. The zwitterionic nido-7,8-carborane derivative
      PPh(3)CH(2)C(2)B(9)H(11) (8) was prepared by treatment of 7 with cesium fluoride
      in refluxing ethanol. All compounds were fully characterized by multinuclear
      ((1)H, (11)B, (13)C, and (31)P) 1D- and 2D-NMR spectroscopy, electrospray
      ionization mass spectrometry, and elemental analysis, and single-crystal X-ray
      structures were determined for compounds 1, 3, 7, and 8. The cytotoxicities and
      boron uptake of selected derivatives were investigated in vitro using human
      glioblastoma (T98G) and canine kidney tubule (MDCK II) cells. The zwitterionic
      species 8 was found to be the least cytotoxic agent while also delivering the
      greatest amount of boron to the T98G cells, peaking at 9.15 +/- 2.65 MUg B/mg
      protein.

PMID- 20694491
TI  - Reply to the letter: "Histology of the internal inguinal ring: it is really a
      novelty?" by Barria et al. Hernia (2010) 14:339-340.

PMID- 20694492
TI  - Cognitive deficits in multiple sclerosis: a review of functional MRI studies.
AB  - Cognitive dysfunction frequently occurs during the course of multiple sclerosis
      (MS). In patients with MS the severity of cognitive manifestations is not closely
      related to indices of structural brain damage. Neuroplasticity may contribute to
      the maintenance of normal performance despite scattered brain lesions. Changes in
      functional organization of the cerebral cortex have been reported by functional
      magnetic resonance imaging (fMRI) studies in MS. fMRI studies provide an
      interesting way of understanding how the brain changes its functional
      organization in response to MS, and might be useful in the study of the effects
      of rehabilitative or pharmacological therapy on brain plasticity. The purpose of
      this review is to examine major fMRI studies focusing on cognitive dysfunction in
      MS.

PMID- 20694493
TI  - The effect of Er:YAG laser irradiation on the scanning electron microscopic
      structure and surface roughness of various implant surfaces: an in vitro study.
AB  - The purpose of this study was to evaluate the surface roughness (R(a)) and
      microscopic change to irradiated dental implant surfaces in vitro and ultimately
      to determine the proper pulse energy power and application time for the clinical
      use of Er:YAG lasers. Anodic oxidized surface implants and sand-blasted, large
      grit, and acid-etched (SLA) surface implants were used. Each experimental group
      of implant surfaces included ten implants. Nine implants were used for the laser
      irradiation test groups and one for the control group. Each test group was
      equally divided into three subgroups by irradiated pulse energy power. Using an
      Er:YAG laser, each subgroup of anodic oxidized surface implants was split into 60
      , 100-, and 140-mJ/pulse groups, with each subgroup of SLA surface implants
      irradiated with a 100-, 140-, or 180-mJ/pulse. Three implants in every test
      subgroup were respectively irradiated for 1, 1.5, and 2 min. The R(a) values for
      each specimen were recorded and every specimen was observed by SEM. Irradiation
      by Er:YAG laser led to a decrease in implant surface roughness that was not
      statistically significant. In anodic oxidized surfaces, the oxidized layer peeled
      off of the surface, and cracks appeared on implant surfaces in the 100- and 140
      mJ/pulse subgroups. However, with SLA surfaces, no significant change in surface
      texture could be found on any implant surface in the 100- and 140-mJ/pulse
      subgroups. The melting and fusion phenomena of implant surfaces were observed
      with all application times with 180 mJ/pulse irradiation. The SLA implant
      surfaces are stable with laser intensities of less than 140 mJ/pulse and an
      irradiation time of less than 2 min. The anodic oxidized surfaces were not stable
      with laser intensities of 100 mJ/pulse when an Er:YAG laser was used to detoxify
      implant surfaces.

PMID- 20694494
TI  - Leiomyosarcoma of the renal vein.
AB  - A 43-year-old woman was referred to our clinic for evaluation of a left
      retroperitoneal mass. She presented to our internal medicine department
      complaining of back pain. Computed tomography (CT) scan revealed a left
      retroperitoneal mass 55 mm in size in the hilum of the left kidney. Enhanced CT
      scan and magnetic resonance imaging (MRI) disclosed a poorly staining mass.
      Metaiodobenzylguanidine scintigraphy demonstrated no accumulation in the mass;
      moreover, endocrinologic examination was normal. Laparoscopic resection of the
      left retroperitoneal tumor was attempted; however, strong adhesion between the
      tumor and the left renal vein was encountered. Thus, left nephrectomy after open
      conversion was performed. Histological findings indicated leiomyosarcoma
      originating from the left renal vein. The postoperative course has been
      uneventful; neither recurrence nor metastasis is evident 2 years postsurgery.

PMID- 20694495
TI  - Salvage repair of anastomotic dehiscence following colon surgery using an
      expanded polytetrafluoroethylene graft.
AB  - Anastomotic dehiscence is a serious complication of colorectal surgery that
      causes death in up to 40% of cases in which it occurs. Edema and inflammation due
      to abdominal sepsis can prevent the use of standard management (i.e., colostomy,
      ileostomy or Hartmann's procedure), in which case alternative salvage repair
      methods are required. The present report describes the treatment of a 73-year-old
      female patient at high risk of mortality because of intraabdominal sepsis due to
      suture dehiscence following a right hemicolectomy and ileo-transversostomy.
      Several surgical repair procedures were tried, but all failed. We then used an
      expanded polytetrafluoroethylene (ePTFE) graft in salvage repair, and this
      approach proved successful. This is the first report to describe clinical,
      macroscopic and histopathological findings, following use of an ePTFE graft in
      colorectal repair in humans.

PMID- 20694496
TI  - Laparoscopic sigmoidectomy for colon cancer.
AB  - The aim of this study is to report our experience with laparoscopic sigmoidectomy
      due to cancer. Between 2007 and 2009, laparoscopic sigmoidectomy for cancer was
      performed in 3 patients. The average operative time was 176 min. The average
      hospital stay was 10.2 days. There was one anastomotic leak. The patient was
      subjected to laparotomy and a Hartmann's procedure and drainage of the peritoneal
      cavity was performed. In conclusion, laparoscopic sigmoidectomy for cancer is a
      safe and efficient procedure.

PMID- 20694497
TI  - Anastomotic leakage following low anterior resection for rectal cancer.
AB  - AIM: Aim of this study is to present the incidence of anastomotic leakage after
      anterior resection for rectal cancer and to demonstrate the therapeutic approach
      for the treatment of this complication. PATIENTS AND METHODS: Between 1990 and
      2009, 170 patients underwent low anterior resection with total mesorectal
      excision (TME). RESULTS: A total of 14 (8.2%) anastomotic leaks were confirmed.
      Reoperation was carried out in six patients with major leaks. Eight patients with
      minor leaks were treated conservatively by nutritional support and antibiotic
      therapy. CONCLUSION: The incidence of anastomotic leakage after anterior
      resection of the rectum for rectal cancer is relatively low.

PMID- 20694498
TI  - Mycophenolate mofetil-induced agranulocytosis in a renal transplant recipient.
AB  - A 27-year-old woman underwent living kidney transplantation from her mother. She
      received basiliximab, tacrolimus, mycophenolate mofetil (MMF), and a
      corticosteroid. Before transplantation, her complete blood count and white cell
      differential were normal. On about the 70th postoperative day (POD 70), her white
      blood cell (WBC) count began to decrease. On POD 113, her WBC count was 2800/MUL.
      There was no evidence of viral infection, other systemic infection or malignancy.
      Drug-induced neutropenia, especially MMF-induced neutropenia, was suspected, and
      the dosage of MMF was reduced. However, the neutrophil count fell to 0/MUL within
      2 weeks. We further reduced the dosage of MMF and administered granulocyte-colony
      stimulating factor (G-CSF), which only temporarily increased the neutrophil
      count. Then, MMF was discontinued and switched to azathioprine, resulting in
      recovery of neutrophil count without subsequent rejection. MMF-induced
      neutropenia frequently occurs and should be monitored not only by WBC count but
      also by white cell differential count, since early discontinuation is the key to
      successful resolution of neutropenia. Switching from MMF to azathioprine or
      administration of G-CSF with or without MMF discontinuation might be options for
      treatment to avoid subsequent rejection.

PMID- 20694500
TI  - The effect of sociodemographic factors on infant mortality according to cause of
      death: a birth cohort in Seoul, Korea, 1999-2003.
AB  - OBJECTIVES: The aim of this study was to examine the effect of socioeconomic
      status and demographic factors on infant mortality, classified by cause of death,
      in a group of children born in Seoul, Korea during 1999-2003. METHODS: Linked
      infant birth and death data were collected from the Korea National Statistical
      Office. Logistic regression models were used to investigate the effect of
      socioeconomic and demographic factors on infant mortality. The results were
      adjusted to take into account the infants' length of gestation and birth weight.
      RESULTS: Infant death rates from all causes tended to decrease as the parents'
      educational level increased. We observed a similar pattern for deaths from other
      specific causes. We also found higher mortality rates for mothers less than 20
      years of age and over 35. CONCLUSIONS: Our analysis shows that socioeconomic and
      demographic factors affect infant mortality. In the case of postneonatal infant
      death, we confirmed that adequate follow-up care can reduce the risks of death
      from these acquired factors. This suggests that these are important factors to
      consider in reducing infant mortality.

PMID- 20694501
TI  - Combining prospective motion correction and distortion correction for EPI:
      towards a comprehensive correction of motion and susceptibility-induced
      artifacts.
AB  - OBJECT: State-of-the-art MR techniques that rely on echo planar imaging (EPI),
      such as real-time fMRI, are limited in their applicability by both subject motion
      and B(0) field inhomogeneities. The goal of this work is to demonstrate that in
      principle it is possible to accurately predict the B(0) field inhomogeneities
      that occur during echo planar imaging in the presence of large scale head motion
      and apply this knowledge for distortion correction. MATERIALS AND METHODS: In
      this work, prospective motion correction is combined with a field-prediction
      method and a method for correcting geometric distortions in EPI. To validate the
      methods, echo planar images were acquired of a custom-made phantom rotated to
      different angles relative to the B(0) field. For each orientation, field maps
      were acquired for comparison with the field predictions. RESULTS: The calculated
      field maps are very similar to the measured field maps for all orientations used
      in the experiments. The root mean squared error (RMSE) of the difference maps was
      between 15 to 20 Hz. The quality of distortion correction using calculated field
      maps is comparable to distortion correction done with measured field maps.
      CONCLUSION: The results suggest that distortion-free echo planar imaging of
      moving objects may be feasible if prospective motion correction is combined with
      a field inhomogeneity estimation approach.

PMID- 20694502
TI  - Increasing temporal resolution of DSC perfusion MRI using the analytic image
      concept.
AB  - OBJECT: Dynamic susceptibility contrast MRI (DSC-MRI) is increasingly being used
      to evaluate cerebral microcirculation. In this study, the use of the analytic
      image reconstruction (AIR), with the aim to increase the temporal resolution, is
      evaluated for DSC-MRI in small animals. MATERIALS AND METHODS: Imaging was
      performed using a T (2)*- weighted sequence to acquire male Lewis rats raw data.
      Results show that AIR satisfactory reconstructs DSC-MRI while preserving a good
      reconstruction quality and the image characteristics compared to the full k-space
      and keyhole reconstructed images. The combination of the choice of the baseline
      image and the proposed asymmetric acquisition schema enables an increase in
      temporal resolution, by a factor of four, thus having more sample points for
      better estimating perfusion parameters. RESULTS: Computer simulations result in a
      mean cerebral blood volume of 1.22 that deviates from the full k-space value by 
      3% and a mean cerebral blood flow of 1.97 deviating from the full k-space value
      by -3% when the mean transit time did not change. Even if these deviations
      increase when achieving real acquisitions, AIR still better computes quantitative
      values than keyhole. CONCLUSION: AIR allows a good reconstruction of the dynamic
      stage of the image series thus leading to better dynamic effects analysis.

PMID- 20694503
TI  - Environmental management for malaria control: knowledge and practices in Mvomero,
      Tanzania.
AB  - Environmental conditions play an important role in the transmission of malaria;
      therefore, regulating these conditions can help to reduce disease burden.
      Environmental management practices for disease control can be implemented at the
      community level to complement other malaria control methods. This study assesses
      current knowledge and practices related to mosquito ecology and environmental
      management for malaria control in a rural, agricultural region of Tanzania.
      Household surveys were conducted with 408 randomly selected respondents from 10
      villages and qualitative data were collected through focus group discussions and
      in-depth interviews. Results show that respondents are well aware of the links
      between mosquitoes, the environment, and malaria. Most respondents stated that
      cleaning the environment around the home, clearing vegetation around the home, or
      draining stagnant water can reduce mosquito populations, and 63% of respondents
      reported performing at least one of these techniques to protect themselves from
      malaria. It is clear that many respondents believe that these environmental
      management practices are effective malaria control methods, but the actual
      efficacy of these techniques for controlling populations of vectors or reducing
      malaria prevalence in the varying ecological habitats in Mvomero is unknown.
      Further research should be conducted to determine the effects of different
      environmental management practices on both mosquito populations and malaria
      transmission in this region, and increased participation in effective techniques
      should be promoted.

PMID- 20694504
TI  - K252a induces anoikis-sensitization with suppression of cellular migration in
      Epstein-Barr virus (EBV)--associated nasopharyngeal carcinoma cells.
AB  - Recent studies revealed an unexpected role of the neurotrophin receptor pathway,
      BDNF/TrkB signaling, in cancer metastasis and anoikis (i.e. detachment-induced
      cell death). Survival of cancer cells in detached state (known as anoikis
      resistance) is known to be pre-requisite for metastasis. Nasopharyngeal carcinoma
      (NPC), an endemic head and neck cancer in Southeast Asia, is highly invasive,
      metastatic, and etiologically associated with Epstein-Barr virus (EBV, an
      oncovirus) infection. Mechanistic studies on the invasive/metastatic nature of
      NPC can facilitate the development of anti-metastatic therapy in NPC. Thus far,
      the role of BDNF/TrkB signaling in virus-associated human cancer is unclear.
      Here, using multiple cell line models of NPC with EBV-association (HONE-1-EBV,
      HK1-LMP1 and C666-1), we investigated the potential involvement of BDNF/TrkB
      signaling in cellular migration and anoikis-resistant characteristics of NPC. We
      found that all three EBV-associated NPC cell lines tested were intrinsically
      anoikis-resistant (i.e. survived in detached state) and expressed both BDNF and
      TrkB. BDNF stimulation induced cellular migration, but not proliferation of these
      cells. Further, we examined if pharmacologic targeting of anoikis-resistance of
      NPC cells can be achievable by a proof-of-concept Trk inhibitor, K252a, in these
      EBV-associated NPC models. Our results demonstrated that K252a, was able to
      attenuate BDNF-induced migration and proliferation of NPC cells. More
      importantly, we demonstrated for the first time that K252a harbored potent
      anoikis-sensitization activity (i.e. sensitizing cancer cells to detachment
      induced cell death) against EBV-associated human cancer cells, namely NPC cells.
      This proof-of-concept study demonstrated that K252a, a Trk inhibitor, can
      potentially be used as an anoikis-sensitizing agent in NPC.

PMID- 20694505
TI  - Facile measurement of 1H-15N residual dipolar couplings in larger perdeuterated
      proteins.
AB  - We present a simple method, ARTSY, for extracting 1J(NH) couplings and 1H-15N
      RDCs from an interleaved set of two-dimensional 1H-15N TROSY-HSQC spectra, based
      on the principle of quantitative J correlation. The primary advantage of the
      ARTSY method over other methods is the ability to measure couplings without
      scaling peak positions or altering the narrow line widths characteristic of TROSY
      spectra. Accuracy of the method is demonstrated for the model system GB3.
      Application to the catalytic core domain of HIV integrase, a 36 kDa homodimer
      with unfavorable spectral characteristics, demonstrates its practical utility.
      Precision of the RDC measurement is limited by the signal-to-noise ratio, S/N,
      achievable in the 2D TROSY-HSQC spectrum, and is approximately given by 30/(S/N)
      Hz.

PMID- 20694506
TI  - Proteomic alterations of Brassica napus root in response to boron deficiency.
AB  - Boron (B) deficiency is a worldwide problem, and Brassica napus is one of the
      most sensitive crops to B deficiency. To better understand the B starvation
      response of Brassica napus, we conducted a comparative proteomic analysis of
      seedling stage Brassica napus root between B-sufficient and B-limited conditions:
      45 differentially expressed proteins were successfully identified by 2-DE coupled
      with MALDI-TOF/TOF-MS and LTQ-ESI-MS/MS analysis. Among these proteins, 10 were
      down-regulated and 35 were up-regulated under B-limited condition. Combining GO
      and KEGG analyses with data from previous reports, proteins were categorized into
      several functional groups, including antioxidant and detoxification, defense
      related proteins, signaling and regulation, carbohydrate and energy metabolism,
      amino acid and fatty acid metabolism, protein translation and degradation, cell
      wall structure, and transporter. The genes of selected proteins were analyzed by
      quantitative RT-PCR. Our results provide novel information for better
      understanding the physiological and biochemical responses to B deficiency in
      plants.

PMID- 20694507
TI  - Mothers of children with developmental disorders in the bedouin community in
      Israel: family functioning, caregiver burden, and coping abilities.
AB  - This preliminary study compares the family functioning, caregiver burden, and
      coping abilities between mothers of 300 children with developmental disorders and
      mothers of 100 children with no such disorders in the Bedouin community in
      Israel. The mothers completed the McMaster Family Assessment Device Scale, the
      Caregiver Burden Index, and the Sense of Coherence Scale. Mothers of children
      with developmental disorders reported lower family functioning, a higher
      caregiver burden, and a lower sense of coherence and thus lower coping abilities
      than mothers of children with no disorders. The study highlights the need to
      provide professional support for mothers of children with developmental disorders
      and to develop awareness and culturally appropriate intervention programs to
      enhance these mothers' coping abilities.

PMID- 20694508
TI  - Anxiety disorders in typically developing youth: autism spectrum symptoms as a
      predictor of cognitive-behavioral treatment.
AB  - Symptoms of autism spectrum disorder (ASD) were assessed (Social Responsiveness
      Scale-Parent (SRS-P); coded in-session behavior) in typically-developing, anxiety
      disordered children (N = 50) treated with cognitive-behavioral therapy (CBT).
      Study 1: children with moderate autistic symptomology (per SRS-P) were
      significantly more likely to improve from family CBT (FCBT) than individual CBT
      (ICBT; OR = 8.67). Coded behavior did not predict outcome. Study 2: CBT
      components were compared by treatment and ASD symptom status. At-home exposure
      completion was greater in FCBT and there was an interaction in child involvement
      for treatment and ASD status. Though both treatments reduced anxiety, FCBT
      outperformed ICBT for children with moderate ASD symptoms, a benefit potentially
      linked to more at-home exposures and greater child involvement in FCBT.

PMID- 20694509
TI  - Male to female and female to male transgender persons have different sexual risk
      behaviors yet similar rates of STDs and HIV.
AB  - The epidemiology of STDs and HIV among male-to-female (MTF) and female-to-male
      (FTM) transgender persons is limited, which makes prevention for transgender
      populations challenging. We examined data collected at visits for all self
      identified MTF and FTM patients at the municipal STD clinic in San Francisco from
      January 1, 2006 to December 31, 2009. We compared demographic and socio
      behavioral characteristics, as well as STD and HIV positivity and history of
      previous STD. Despite demographic and behavioral risk differences, there were no
      differences in STD positivity or HIV prevalence between MTF and FTM. A more
      complete understanding of the prevention needs for transgender persons is needed.

PMID- 20694510
TI  - Latent class analysis of sexual risk patterns among esquineros (street corner
      men) a group of heterosexually identified, socially marginalized men in urban
      coastal Peru.
AB  - We explored patterns of sexual risk behavior among esquineros, heterosexually
      identified, socially-marginalized Peruvian men using latent class analysis. We
      used data from the Peru site of the National Institute of Mental Health (NIMH)
      Collaborative HIV/STD Prevention Trial which included n = 2,109 heterosexually
      identified men. The latent class analysis used seven risk behaviors to group
      esquineros into risk classes. We identified four latent classes, of which two
      classes had lower probabilities and two classes had higher probabilities of these
      risk behaviors. Comparing the two lower risk classes to the two higher risk
      classes yielded significantly more unprotected sex acts (Chi square P value <
      0.001). The risk behaviors in two of the latent classes identified were primarily
      related to alcohol and drug use. Future HIV/STI prevention interventions may
      benefit from this information by tailoring messages to fit the observed risk
      patterns and should focus on drug and alcohol use.

PMID- 20694511
TI  - Organochlorine pesticides in the surface water and sediments from the Peacock
      River Drainage Basin in Xinjiang, China: a study of an arid zone in Central Asia.
AB  - Fourteen surface water and nine surface sediment samples were collected from the
      Peacock River and analyzed for organochlorine pesticides (OCPs) by gas
      chromatograph-electron capture detector (GC-ECD). All the analyzed organochlorine
      pesticides, except o,p'-DDT, were detected in sediments from the Peacock River;
      but in the water samples, only beta-HCH, HCB, p,p'-DDD, and p,p'-DDT were
      detected at some sites. The ranges for total OCPs in the water and sediments were
      from N.D. to 195 ng l( - 1) and from 1.36 to 24.60 ng g( - 1), respectively. The
      only existing HCH isomer in the water, beta-HCH, suggested that the contamination
      by HCHs could be attributed to erosion of the weathered agricultural soils
      containing HCHs compounds. Composition analyses showed that no technical HCH,
      technical DDT, technical chlordanes, endosulfans, and HCB had been recently used
      in this region. However, there was new input of gamma-HCH (lindane) into the
      Peacock River. The most probable source was water flowing from Bosten Lake and/or
      agricultural tailing water that was returned directly into the Peacock River. DDT
      compounds in the sediments may be derived mainly from DDT-treated aged and
      weathered agricultural soils, the degradation condition was aerobic and the main
      product was DDE. HCB in the sediment might be due to the input from Bosten Lake
      and the lake may act as an atmospheric deposition zone. There was no significant
      correlation between the concentrations of OCPs (including ?HCH, ?DDT, chlordanes,
      endosulfans, HCB and total OCPs) and the content of fine particles (<63 MUm). The
      concentrations of OCPs were affected by salinity.

PMID- 20694512
TI  - Role of EUS-FNA-based cytology in the diagnosis of mucinous pancreatic cystic
      lesions: a systematic review and meta-analysis.
AB  - BACKGROUND: Preoperative diagnosis of malignancy in pancreatic cystic lesions
      (PCLs) remains challenging. Most non-mucinous cystic lesions (NMCLs) are benign,
      but mucinous cystic lesions (MCLs) are more likely to be premalignant or
      malignant. AIM: The aim of this study was to assess the sensitivity, specificity,
      and positive and negative likelihood ratios (LRs) of EUS-FNA-based cytology in
      differentiating MCLs from non-mucinous PCLs. METHODS: We conducted a
      comprehensive search of MEDLINE, SCOPUS, Cochrane, and "CINAHL Plus" databases to
      identify studies, in which the results of EUS-FNA-based cytology of PCLs were
      compared with those of surgical biopsy or surgical excision histopathology. A
      DerSimonian-Laird random effect model was used to estimate the pooled
      sensitivity, specificity, and LRs, and a summary receiver-operating
      characteristic (SROC) curve was constructed. RESULTS: We included 376 patients
      from 11 distinct studies who underwent EUS-FNA-based cytology and also had
      histopathological diagnosis. The pooled sensitivity and specificity in diagnosing
      MCLs were 0.63 (95% CI, 0.56-0.70) and 0.88 (95% CI, 0.83-0.93), respectively.
      The positive and negative LRs in diagnosing MCLs were 4.46 (95% CI, 1.21-16.43)
      and 0.46 (95% CI, 0.25-0.86), respectively. The area under the curve (AUC) was
      0.89. CONCLUSIONS: EUS-FNA-based cytology has overall low sensitivity but good
      specificity in differentiating MCLs from NMCLs. Further research is required to
      improve the overall sensitivity of EUS-FNA-based cytology to diagnose MCLs while
      evaluating PCL.

PMID- 20694513
TI  - MCM-2 and MCM-5 expression in gastric adenocarcinoma: clinical significance and
      comparison with Ki-67 proliferative marker.
AB  - BACKGROUND: Minichromosome maintenance (MCM) proteins are essential components of
      DNA replication, being related to cell proliferation, and serve as useful
      biomarkers for cancer screening, surveillance and prognosis. The aim of the
      present study was to evaluate the clinical significance of MCM-2 and MCM-5
      expression in gastric adenocarcinoma in comparison with Ki-67 proliferative
      marker. METHODS: MCM-2, MCM-5 and Ki-67 expression was assessed
      immunohistochemically in 66 tumoral samples of gastric adenocarcinoma patients
      and was statistically analyzed in relation to clinicopathological characteristics
      and patient survival. RESULTS: MCM-2 expression did not show significant
      associations with any clinicopathological parameters, while Ki-67 expression was
      merely significantly associated with tumor size (P = 0.0150). MCM-2 and Ki-67
      expression were more frequently in intestinal (median values: 67.5 and 60%)
      compared to diffuse-type (median values: 60 and 45%) gastric adenocarcinoma cases
      without though reaching statistical significance (P > 0.05). MCM-5 expression was
      significantly associated with tumor size (P = 0.0295), presence of lymph node
      metastases (P = 0.0216) and tumor histopathological stage (P = 0.0098). Patients
      presenting high MCM-5 expression had significantly shorter survival times (log
      rank test, P = 0.0042), whereas neither MCM-2 nor Ki-67 expression showed
      significant prognostic value (log-rank test, P = 0.9618 and P = 0.7174,
      respectively). In multivariate analysis, patient age, histopathological stage and
      grade of differentiation, but not MCM-5 expression, were identified as
      independent prognostic factors (Cox regression analysis, P = 0.0097, P = 0.0195,
      P = 0.0035 and P = 0.3245, respectively). CONCLUSIONS: The present study showed
      that MCM-5 expression was associated with clinicopathological parameters in
      gastric adenocarcinoma. However, further studies highlighting the distinct impact
      of the two histopathological types, intestinal and diffuse, are warranted to
      delineate whether MCMs could be used as diagnostic and prognostic markers in
      gastric neoplasia.

PMID- 20694514
TI  - EMDR treatment in people with mild ID and PTSD: 4 cases.
AB  - Although there is evidence to suggest that people with intellectual disabilities
      (ID) are likely to be more susceptible to the development of posttraumatic stress
      disorder (PTSD) than persons in the general population, until now only eight case
      reports on the treatment of people with ID suffering from PTSD symptoms have been
      published. In an effort to enrich the literature on this subject, the aim was to
      investigate the applicability of an evidence-based treatment for PTSD (i.e.,
      EMDR) in four people with mild ID, suffering from PTSD following various kinds of
      trauma. In all cases PTSD symptoms decreased and the gains were maintained at 3
      months to 2.5 year follow-up. In addition, depressive symptoms and physical
      complaints subsided, and social and adaptive skills improved. It is concluded
      that clients' improvements converge to suggest the applicability of EMDR in
      people with mild ID. Difficulties involved in arriving at an accurate PTSD
      diagnosis in ID clients are discussed.

PMID- 20694516
TI  - Thermal conduction tensor imaging and energy flow analysis of brain: a
      feasibility study using MRI.
AB  - The imaging of the distribution of thermal conductivity tensor at various points
      in a tissue is an essential need when accurate knowledge of heat energy flow in
      tissue is required for diagnostic and therapeutic management in oncology,
      neurology, and interventional radiology. Conventionally, tissue thermal
      conductivity is assumed as scalar, which induces errors in obtaining proper heat
      flow distribution. Using statistical thermodynamics principles, we present a
      method for constructing thermal conductivity tensor image of a tissue or an
      organ, using an MRI scanner. We elucidate the necessary tensorial cross-property
      relationship between different transport processes and confirm the same by
      experimental data. Using the proposed method, we perform a preliminary study of
      the procedure of thermal conductivity tensor imaging of the human brain as a case
      study. The methodology is quantitatively elucidated by measurement of tissue
      anisotropy distribution, tensor eigenvalues, and path tracking, along with three
      illustrative examples showing that transport properties estimated by the proposed
      thermal conductivity approach closely corroborates, with over 90% accuracy, to
      the experimentally measured values of the transport parameters which have been
      independently experimentally measured directly. By combining diffusion and
      perfusion tensor imaging approaches using mobility-encoding and spin-labelling
      methodologies respectively, we delineate the possible applications of this novel
      imaging modality to clinical problems of energy flow mapping involving biological
      heat transfer equations, such as planning of hyperthermic treatment to brain
      tumors, and electrode localization for deep brain stimulation in Parkinson's
      disease.

PMID- 20694515
TI  - A purging procedure for pantoprazole and 4-lumen catheters to prevent IV drug
      incompatibilities.
AB  - OBJECTIVE OF THE STUDY: The purpose of this prospective intervention study was to
      assess the number of patients with Y-site incompatibilities before and after
      implementation of quality improvement measures to prevent incompatibilities
      consisting of a focused instruction for pantoprazole as a drug frequently
      involved in incompatible drug pairs and of a recommendation to use 4-lumen
      instead of 3-lumen catheters to increase the number of available central infusion
      lines. SETTING: Cardiovascular intensive care unit where several standard
      operating procedures (SOPs) dealing with compatibility were already in place.
      METHOD: In a prospective intervention study, patients' IV medication was assessed
      for potential incompatibilities using a database containing compatibility
      information on approximately 60,000 drug pairs. In a first period, routine
      administration was monitored in 53 consecutive patients (control group). Then,
      quality improvement measures were implemented recommending a purging procedure
      before and after bolus administration of pantoprazole as a drug frequently
      causing incompatibilities in this setting. Additionally, the use of 4-lumen
      instead of 3-lumen catheters was suggested whenever considered useful by the
      responsible physicians. The monitoring was repeated during a second period in
      another 58 patients consecutively admitted to the same unit (intervention group).
      MAIN OUTCOME MEASURE: Overall number of patients with at least one incompatible
      drug pair and number of patients receiving incompatible pantoprazole
      combinations. RESULTS: The number of patients receiving incompatible pantoprazole
      combinations decreased from 15 of the 15 patients receiving pantoprazole (100.0%)
      in controls to 9/16 (56.2%) in the intervention group (P < 0.01). The overall
      number of patients with incompatibilities was not influenced by the intervention
      with 36/58 (62.1%) compared to controls with 38/53 (71.7%, P = 0.28). The
      fraction of central lines contributed by four lumen central catheters was larger
      due to the intervention (80/168 lines, 47.6%) compared to controls (16/184, 8.7%,
      P < 0.001). Only sporadically there were incompatible combinations of drugs
      governed by the already existing SOPs. CONCLUSION: In an intensive care setting
      with good SOP adherence, purging before and after administration decreased the
      respective incompatibility rate whereas the use of 4-lumen instead of 3- lumen
      catheters had not the expected benefit on separating drug pairs.

PMID- 20694517
TI  - Simultaneous LC-MS/MS determination of phenylbutyrate, phenylacetate benzoate and
      their corresponding metabolites phenylacetylglutamine and hippurate in blood and
      urine.
AB  - Inborn errors of urea metabolism result in hyperammonemia. Treatment of urea
      cycle disorders can effectively lower plasma ammonium levels and results in
      survival in the majority of patients. Available medications for treating urea
      cycle disorders include sodium benzoate (BA), sodium phenylacetate (PAA), and
      sodium phenylbutyrate (PBA) and are given to provide alternate routes for
      disposition of waste nitrogen excretion. In this study, we develop and validate a
      liquid chromatography tandem mass spectrometry (LC-MS/MS) method for simultaneous
      determination of benzoic acid, phenylacetic acid, phenylbutyric acid,
      phenylacetylglutamine, and hippuric acid in plasma and urine from children with
      inborn errors of urea synthesis. Plasma extracts and diluted urine samples were
      injected on a reverse-phase column and identified and quantified by selected
      reaction monitoring (SRM) in negative ion mode. Deuterated analogues served as
      internal standards. Analysis time was 7 min. Assay precision, accuracy, and
      linearity and sample stability were determined using enriched samples.
      Quantification limits of the method were 100 ng/ml (0.3-0.8 MUmol/L) for all
      analytes, and recoveries were >90%. Inter- and intraday relative standard
      deviations were <10%. Our newly developed LC-MS/MS represents a robust,
      sensitive, and rapid method that allows simultaneous determination of the five
      compounds in plasma and urine.

PMID- 20694520
TI  - Genetic modification of T cells improves the effectiveness of adoptive tumor
      immunotherapy.
AB  - Appropriate combinations of immunotherapy and gene therapy promise to be more
      effective in the treatment of cancer patients than either of these therapeutic
      approaches alone. One such treatment is based on the application of patients'
      cytotoxic T cells, which can be activated, expanded, and genetically engineered
      to recognize particular tumor-associated antigens (TAAs). Because T cells
      recognizing TAAs might become unresponsive in the process of tumor development as
      a result of tumor evasion strategies, immunogenic viral antigens or alloantigens
      could be used for the expansion of cytotoxic T cells and then redirected through
      genetic engineering. This therapeutic approach has already demonstrated promising
      results in melanoma patients and could be used in the treatment of many other
      tumors. The graft-versus-leukemia, or more generally graft-versus-tumor, reaction
      based on the application of a donor lymphocyte infusion can also be ameliorated
      through the incorporation of suicide genes into donor lymphocytes. Such
      lymphocytes could be safely and more extensively used in tumor patients because
      they could be eliminated should a severe graft-versus-host reaction develop.

PMID- 20694518
TI  - High-fidelity patch-clamp recordings from neurons cultured on a polymer
      microchip.
AB  - We present a polymer microchip capable of monitoring neuronal activity with a
      fidelity never before obtained on a planar patch-clamp device. Cardio-respiratory
      neurons Left Pedal Dorsal 1 (LPeD1) from mollusc Lymnaea were cultured on the
      microchip's polyimide surface for 2 to 4 hours. Cultured neurons formed high
      resistance seals (gigaseals) between the cell membrane and the surface
      surrounding apertures etched in the polyimide. Gigaseal formation was observed
      without applying external force, such as suction, on neurons. The formation of
      gigaseals, as well as the low access resistance and shunt capacitance values of
      the polymer microchip resulted in high-fidelity recordings. On-chip culture of
      neurons permitted, for the first time on a polymeric patch-clamp device, the
      recording of high fidelity physiological action potentials. Microfabrication of
      the hybrid poly(dimethylsiloxane)-polyimide (PDMS-PI) microchip is discussed,
      including a two-layer PDMS processing technique resulting in minimized shrinking
      variations.

PMID- 20694521
TI  - Grid-based implementation of XDS-I as part of image-enabled EHR for regional
      healthcare in Shanghai.
AB  - PURPOSE: Due to the rapid growth of Shanghai city to 20 million residents, the
      balance between healthcare supply and demand has become an important issue. The
      local government hopes to ameliorate this problem by developing an image-enabled
      electronic healthcare record (EHR) sharing mechanism between certain hospitals.
      This system is designed to enable healthcare collaboration and reduce healthcare
      costs by allowing review of prior examination data obtained at other hospitals.
      Here, we present a design method and implementation solution of image-enabled
      EHRs (i-EHRs) and describe the implementation of i-EHRs in four hospitals and one
      regional healthcare information center, as well as their preliminary operating
      results. METHODS: We designed the i-EHRs with service-oriented architecture (SOA)
      and combined the grid-based image management and distribution capability, which
      are compliant with IHE XDS-I integration profile. There are seven major
      components and common services included in the i-EHRs. In order to achieve quick
      response for image retrieving in low-bandwidth network environments, we use a
      JPEG2000 interactive protocol and progressive display technique to transmit
      images from a Grid Agent as Imaging Source Actor to the PACS workstation as
      Imaging Consumer Actor. RESULTS: The first phase of pilot testing of our image
      enabled EHR was implemented in the Zhabei district of Shanghai for imaging
      document sharing and collaborative diagnostic purposes. The pilot testing began
      in October 2009; there have been more than 50 examinations daily transferred
      between the City North Hospital and the three community hospitals for
      collaborative diagnosis. The feedback from users at all hospitals is very
      positive, with respondents stating the system to be easy to use and reporting no
      interference with their normal radiology diagnostic operation. CONCLUSIONS: The i
      EHR system can provide event-driven automatic image delivery for collaborative
      imaging diagnosis across multiple hospitals based on work flow requirements. This
      project demonstrated that the grid-based implementation of IHE XDS-I for image
      enabled EHR could scale effectively to serve a regional healthcare solution with
      collaborative imaging services. The feedback from users of community hospitals
      and large hospital is very positive.

PMID- 20694522
TI  - Efficient physics-based tracking of heart surface motion for beating heart
      surgery robotic systems.
AB  - PURPOSE: Tracking of beating heart motion in a robotic surgery system is required
      for complex cardiovascular interventions. METHODS: A heart surface motion
      tracking method is developed, including a stochastic physics-based heart surface
      model and an efficient reconstruction algorithm. The algorithm uses the
      constraints provided by the model that exploits the physical characteristics of
      the heart. The main advantage of the model is that it is more realistic than most
      standard heart models. Additionally, no explicit matching between the
      measurements and the model is required. The application of meshless methods
      significantly reduces the complexity of physics-based tracking. RESULTS: Based on
      the stochastic physical model of the heart surface, this approach considers the
      motion of the intervention area and is robust to occlusions and reflections. The
      tracking algorithm is evaluated in simulations and experiments on an artificial
      heart. Providing higher accuracy than the standard model-based methods, it
      successfully copes with occlusions and provides high performance even when all
      measurements are not available. CONCLUSIONS: Combining the physical and
      stochastic description of the heart surface motion ensures physically correct and
      accurate prediction. Automatic initialization of the physics-based cardiac motion
      tracking enables system evaluation in a clinical environment.

PMID- 20694523
TI  - The novel role of fenofibrate in preventing nicotine- and sodium arsenite-induced
      vascular endothelial dysfunction in the rat.
AB  - The present study investigated the effect of fenofibrate, an agonist of PPAR
      alpha, in nicotine- and sodium arsenite-induced vascular endothelial dysfunction
      (VED) in rats. Nicotine (2 mg/kg/day, i.p., 4 weeks) and sodium arsenite (1.5
      mg/kg/day, i.p., 2 weeks) were administered to produce VED in rats. The scanning
      electron microscopy study in thoracic aorta revealed that administration of
      nicotine or sodium arsenite impaired the integrity of vascular endothelium.
      Further, administration of nicotine or sodium arsenite significantly decreased
      serum and aortic concentrations of nitrite/nitrate and subsequently reduced
      acetylcholine-induced endothelium-dependent relaxation. Moreover, nicotine or
      sodium arsenite produced oxidative stress by increasing serum thiobarbituric acid
      reactive substances (TBARS) and aortic superoxide generation. However, treatment
      with fenofibrate (30 mg/kg/day, p.o.) or atorvastatin (30 mg/kg/day p.o., a
      standard agent) significantly prevented nicotine- and sodium arsenite-induced VED
      and oxidative stress by improving the integrity of vascular endothelium,
      increasing the concentrations of serum and aortic nitrite/nitrate, enhancing the
      acetylcholine-induced endothelium-dependent relaxation and decreasing serum TBARS
      and aortic superoxide anion generation. Conversely, co-administration of L-NAME
      (25 mg/kg/day, i.p.), an inhibitor of nitric oxide synthase, markedly attenuated
      these vascular protective effects of fenofibrate. The administration of nicotine
      or sodium arsenite altered the lipid profile by increasing serum cholesterol and
      triglycerides and consequently decreasing high-density lipoprotein levels, which
      were significantly prevented by treatment with fenofibrate or atorvastatin. It
      may be concluded that fenofibrate improves the integrity and function of vascular
      endothelium, and the vascular protecting potential of fenofibrate in preventing
      the development of nicotine- and sodium arsenite-induced VED may be attributed to
      its additional properties (other than lipid lowering effect) such as activation
      of eNOS and generation of NO and consequent reduction in oxidative stress.

PMID- 20694524
TI  - Electrolyte orders in the neuroscience intensive care unit: worth the value or
      waste?
AB  - BACKGROUND: To assess the value of the practice of obtaining frequent electrolyte
      measurements in patients with extended stay in a neuroscience intensive care unit
      (NICU). METHODS: We identified consecutive patients 18 years or older, admitted
      to the NICU between January 1 and July 31, 2009 with length of stay >= 5 days. We
      collected potassium, sodium, magnesium, ionized calcium, phosphorus laboratory
      measurements and hemoglobin levels, and recorded electrolyte replacement orders
      and red blood cell transfusions. Average laboratory costs were estimated.
      RESULTS: 93 patients were included in the study (54 men, mean age 54 years, range
      18-85 years). Mean length of stay was 10.4 days (range 5-36 days). Sodium and
      potassium were the electrolytes most frequently measured (averages of 14.1 and
      13.1 per patient, respectively). More than 75% of the results were within normal
      range for all electrolytes measured and critical values were extremely uncommon.
      The number of phlebotomies for electrolyte measurements was strongly associated
      with the degree of hemoglobin drop (P < 0.0001). Electrolyte panels were ordered
      much more often than individual electrolytes with average cost exceeding $2200
      per patient. Replacing half of these electrolyte panels with single sodium or
      potassium orders would have resulted in savings greater than $100,000 in our
      population. CONCLUSIONS: Electrolytes measurements are very frequent in the NICU,
      but results are most often normal and only exceptionally critical. The
      phlebotomies required for these tests significantly worsen hemoglobin levels. A
      more conservative use of electrolyte measurements can result in reduction of
      blood loss and substantial cost savings.

PMID- 20694525
TI  - Clinical experience with transcranial Doppler ultrasonography as a confirmatory
      test for brain death: a retrospective analysis.
AB  - BACKGROUND: Transcranial Doppler (TCD) ultrasonography to demonstrate cerebral
      circulatory arrest (CCA) is a confirmatory test for brain death (BD). The primary
      aim of this retrospective study was to evaluate the practical utility of TCD to
      confirm BD when clinical diagnosis was not feasible due to confounding factors.
      Secondary aims were to evaluate the reasons for inability of TCD to confirm BD
      and to assess the outcome of patients not brain dead according to the TCD
      criteria. METHODS: TCD waveforms and medical records of all the patients examined
      to confirm suspected BD between 2001 and 2007, where clinical diagnosis was not
      possible, were analyzed. BD was diagnosed based on CCA criteria recommended by
      the Task Force Group on cerebral death of the Neurosonology Research Group of the
      World Federation of Neurology. Final outcome of patients and the use of other
      ancillary tests were noted. RESULTS: Ninety patients (61 males), aged 40 +/- 21
      (range 3-84) years underwent TCD examination for confirmation of suspected BD.
      TCD confirmed BD in 51 (57%) patients and was inconclusive in 38 (43%), with no
      flow signals on the first examination in 7 (8%) patients and the waveform
      patterns in 31 (35%) being inconsistent with BD. Fourteen of the 19 patients who
      had CCA pattern in at least one artery but did not meet all the criteria for BD
      were subsequently found brain dead according to SPECT/clinical criteria or
      suffered cardiovascular death. CONCLUSION: Using the conventional criteria, TCD
      confirmed BD in a large proportion, of patients where clinical diagnosis could
      not be made. The presence of CCA pattern in one or more major cerebral artery may
      be prognostic of unfavorable outcome, even when BD criteria are not satisfied.

PMID- 20694526
TI  - Simultaneous delivery of chemotherapeutic and thermal-optical agents to cancer
      cells by a polymeric (PLGA) nanocarrier: an in vitro study.
AB  - PURPOSE: To test the effectiveness of a dual-agent-loaded PLGA nanoparticulate
      drug delivery system containing doxorubicin (DOX) and indocyanine green (ICG) in
      a DOX-sensitive cell line and two resistant cell lines that have different
      resistance mechanisms. METHODS: The DOX-sensitive MES-SA uterine sarcoma cell
      line was used as a negative control. The two resistant cell lines were uterine
      sarcoma MES-SA/Dx5, which overexpresses the multidrug resistance exporter P
      glycoprotein, and ovarian carcinoma SKOV-3, which is less sensitive to
      doxorubicin due to a p53 gene mutation. The cellular uptake, subcellular
      localization and cytotoxicity of the two agents when delivered via nanoparticles
      (NPs) were compared to their free-form administration. RESULTS: The cellular
      uptake and cytotoxicity of DOX delivered by NPs were comparable to the free form
      in MES-SA and SKOV-3, but much higher in MES-SA/Dx5, indicating the capability of
      the NPs to overcome P-glycoprotein resistance mechanisms. NP-encapsulated ICG
      showed slightly different subcellular localization, but similar fluorescence
      intensity when compared to free ICG, and retained the ability to generate heat
      for hyperthermia delivery. CONCLUSION: The dual-agent-loaded system allowed for
      the simultaneous delivery of hyperthermia and chemotherapy, and this
      combinational treatment greatly improved cytotoxicity in MES-SA/Dx5 cells and to
      a lesser extent in SKOV-3 cells.

PMID- 20694528
TI  - Male-specific cuticular compounds of the six Drosophila paulistorum semispecies:
      structural identification and mating effect.
AB  - We have identified cuticular pheromones that sustain the integrity of the six
      Drosophila paulistorum semispecies. Hexane extracts of male and female cuticles
      were separated on a silica gel column and analyzed using gas chromatography/mass
      spectrometry. Both sexes of each of the six semispecies have the same fifteen
      major cuticular components, all hydrocarbons ranging from C31 to C37. However,
      all males have four additional ester compounds. Bioassay observations showed that
      this four-component ester complex imparts a strong anti-aphrodisiac effect on
      intra-semispecific mating behavior, thus confirming its pheromonal role. The
      three major ester components are methyl (Z)-9-tetradecenoate (C(15)H(28)O(2)), 11
      docosenyl acetate (C(24)H(46)O(2)), and 19-triacontenyl acetate (C(32)H(62)O(2)).
      The fourth ester is a di-unsaturated acetate with molecular formula
      C(32)H(60)O(2), but the positions of unsaturation have not been determined.
      Bioassays indicate that the male-specific complex of the transitional
      semispecies, the relict ancestor, imparts anti-aphrodisiac effects on the other
      semispecies as well, but effectiveness decreases with phylogenetic distances.
      Across the six semispecies, the male-specific compounds are the same, but vary
      quantitatively. Apparently, the quantitative differences among these incipient
      species act efficiently to preclude hybridization in nature. Because Drosophila
      paulistorum is a cluster of incipient species, this opportunity to observe
      pheromonal influences on speciation is unique.

PMID- 20694527
TI  - Poly(I:C)-mediated tumor growth suppression in EGF-receptor overexpressing tumors
      using EGF-polyethylene glycol-linear polyethylenimine as carrier.
AB  - PURPOSE: To develop a novel polyethylenimine (PEI)-based polymeric carrier for
      tumor-targeted delivery of cytotoxic double-stranded RNA
      polyinosinic:polycytidylic acid, poly(I:C). The novel carrier should be
      chemically less complex but at least as effective as a previously developed tetra
      conjugate containing epidermal growth factor (EGF) as targeting ligand,
      polyethylene glycol (PEG) as shielding spacer, 25 kDa branched PEI as RNA binding
      and endosomal buffering agent, and melittin as endosomal escape agent. METHODS:
      Novel conjugates were designed employing a simplified synthetic strategy based on
      22 kDa linear polyethylenimine (LPEI), PEG spacers, and recombinant EGF. The
      efficacy of various conjugates (different PEG spacers, with and without targeting
      EGF) in poly(I:C)-mediated cell killing was evaluated in vitro using two human
      U87MG glioma cell lines. The most effective polyplex was tested for in vivo
      activity in A431 tumor xenografts. RESULTS: Targeting conjugate LPEI-PEG2 kDa-EGF
      was found as most effective in poly(I:C)-triggered killing of tumor cells in
      vitro. The efficacy correlated with glioma cell EGFR levels. Repeated intravenous
      administration of poly(I:C) polypexes strongly retarded growth of A431 human
      tumor xenograft in mice. CONCLUSIONS: The optimized LPEI-PEG2 kDa-EGF conjugate
      displays reduced chemical complexity and efficient poly(I:C)-mediated killing of
      EGFR overexpressing tumors in vitro and in vivo.

PMID- 20694529
TI  - Market Basket Analysis: a new tool in ecology to describe chemical relations in
      the environment--a case study of the fern Athyrium distentifolium in the Tatra
      National Park in Poland.
AB  - In this study, the novel data mining technique Market Basket Analysis (MBA) was
      applied for the first time in biogeochemical and ecological investigations. The
      method was tested on the fern Athyrium distentifolium, in which we measured
      concentrations of the elements Ca, Cd, Cr, Cu, Fe, K, Mg, Mn, Na, Ni, Pb, and Zn.
      Plants were sampled from sites with different types of bedrock in the Tatra
      National Park in Poland. MBA was used to investigate whether specimens of
      Athyrium distentifolium that contain elevated levels of certain elements occur
      more frequently on a specific type of bedrock and to identify relationships
      between the type of bedrock and the concentrations of the elements in this fern.
      The results were compared with those of the commonly used principal component and
      classification analysis (PCCA) technique. MBA and PCCA ordination both yielded
      distinct groups of ferns growing on different types of bedrock. Although the
      results of MBA and PCCA were similar, MBA has the advantage of being independent
      of the size of the data set. In addition, MBA revealed not only dominant elements
      but, in the case of limestone bedrock, also showed very low concentrations of Cd,
      Fe, Mn, and Pb in ferns growing on this type of parent material. MBA, thus,
      appeared to be a promising data mining method to reveal chemical relations in the
      environment as well as the accumulation of chemical elements in bioindicators.
      This technique can be used to reveal associations and correlations among items in
      large data sets collected on a national or even larger scale.

PMID- 20694530
TI  - Chronic kidney disease and albuminuria in arterial hypertension.
AB  - Chronic kidney disease is a major public health problem worldwide: it is
      estimated that in the general population, 1 person in 10 has some degree of renal
      damage. Adequate blood pressure control represents the mainstay of treatment, to
      delay deterioration of renal function and prevent cardiovascular complications.
      Current evidence supports a target blood pressure value of 130/80 mm Hg or less
      (ie, <125/75 mm Hg) when proteinuria exceeds 1 g/L. Angiotensin-converting enzyme
      inhibitors or angiotensin II receptor blockers represent the treatment of choice,
      especially in the presence of proteinuria. More complete blockade of the renin
      angiotensin-aldosterone system (RAAS) has been advocated, using a combination of
      multiple RAAS blocker drugs or supramaximal doses to maximize renal protection.
      Achieving recommended blood pressure target values usually requires the use of
      multiple antihypertensive drugs, including diuretics and calcium channel
      blockers.

PMID- 20694532
TI  - Use of foscarnet for cytomegalovirus infection after allogeneic hematopoietic
      stem cell transplantation from a related donor.
AB  - Foscarnet is an active agent against cytomegalovirus (CMV) infection after
      hematopoietic stem cell transplantation (HSCT), as well as ganciclovir. We
      investigated the usefulness of foscarnet in patients who underwent related
      allogeneic HSCT. Foscarnet was used in 320 patients with a median age of 45 years
      (range 15-72). The purpose of administration was CMV disease in 65, preemptive
      use in 248 and prophylaxis in 7. Totally, 194 patients had a history of prior
      ganciclovir treatment. The reason for foscarnet use was insufficient therapeutic
      effect of prior ganciclovir in 99, and adverse event including myelosuppression
      in 95. The response rate in symptom was 52% for the CMV disease patients.
      Antigenemia disappeared in 77% of the preemptive treatment and improved in 13% of
      the patients. No outbreak of CMV disease was recognized. The total effectiveness
      of therapeutic and preemptive use was significantly higher for patients without
      prior ganciclovir (91 vs. 76%, P = 0.001). Adverse events of grade 3 or higher
      were recognized in 24%, including electrolyte abnormalities in 11%, neutropenia
      in 8%, and thrombocytopenia in 8%. Renal damage was only observed in 3% of
      patients. Foscarnet was concluded to be a safe and effective anti-CMV agent and
      to be a suitable alternative to ganciclovir.

PMID- 20694531
TI  - Rare causes of dystonia parkinsonism.
AB  - The list of genetic causes of syndromes of dystonia parkinsonism grows
      constantly. As a consequence, the diagnosis becomes more and more challenging for
      the clinician. Here, we summarize the important causes of dystonia parkinsonism
      including autosomal-dominant, recessive, and x-linked forms. We cover dopa
      responsive dystonia, Wilson's disease, Parkin-, PINK1-, and DJ-1-associated
      parkinsonism (PARK2, 6, and 7), x-linked dystonia-parkinsonism/Lubag (DYT3),
      rapid-onset dystonia-parkinsonism (DYT12) and DYT16 dystonia, the syndromes of
      Neurodegeneration with Brain Iron Accumulation (NBIA) including pantothenate
      kinase (PANK2)- and PLA2G6 (PARK14)-associated neurodegeneration,
      neuroferritinopathy, Kufor-Rakeb disease (PARK9) and the recently described SENDA
      syndrome; FBXO7-associated neurodegeneration (PARK15), autosomal-recessive
      spastic paraplegia with a thin corpus callosum (SPG11), and dystonia parkinsonism
      due to mutations in the SLC6A3 gene encoding the dopamine transporter. They have
      in common that in all these syndromes there may be a combination of dystonic and
      parkinsonian features, which may be complicated by pyramidal tract involvement.
      The aim of this review is to familiarize the clinician with the phenotypes of
      these disorders.

PMID- 20694533
TI  - Optimization of immunomagnetic selection of myeloma cells from bone marrow using
      magnetic activated cell sorting.
AB  - Plasma cells (PCs) enrichment from bone marrow samples of multiple myeloma (MM)
      patients is frequently performed by immunomagnetic separation (magnetic activated
      cell sorting, MACS) using anti-CD138 MicroBeads. The aim of our work was to find
      optimal strategy for immunomagnetic separation of PCs and determine optimal
      algorithm of separation techniques for samples with various percentage of
      neoplastic cells. From 2007 to 2008, selection of PCs using separation programs
      Possels and Posseld(2) was carried out on 234 bone marrow samples obtained from
      208 MM patients. In 2008, an optimal algorithm for separation programs was
      introduced based on the analysis of the previous experiments. The Possels program
      is applicable for samples with >10% PCs in the mononuclear fraction, while the
      Posseld(2) program is used for samples with 5-10% PCs in the mononuclear
      fraction. Median purity of 92.6% for the positive fraction of cells (range 14.5
      99.6%) and median recovery of 60.4% (range 25.7-99.5%) were obtained when the
      Possels program was applied (n = 45). A total of 80% (36/45) of processed samples
      had purity of >70%. Median purity for the positive fraction of 83.7% (range 14.3
      99.7%) and median recovery of 14.3% (range 3.6-50.0%) were achieved using the
      Posseld(2) program (n = 99). A total of 68% (67/99) of processed samples reached
      >70% purity. This separation strategy enabled us to obtain sufficient amounts of
      highly purified PCs required for subsequent research purposes. The MACS method
      has been unsuccessful if the percentage of PCs in the initial sample was <5%.
      These samples were processed by fluorescence activated cell sorting (FACS).

PMID- 20694534
TI  - Formulation of dacarbazine-loaded cubosomes. Part III. Physicochemical
      characterization.
AB  - The purpose of this study was to investigate the physicochemical properties of
      dacarbazine-loaded cubosomes. The drug-loaded cubosome nanocarriers were prepared
      by a fragmentation method and then freeze dried. They were then characterized for
      size, morphology, thermal behavior, and crystallography using dynamic light
      scattering, transmission electron microscopy (TEM), differential scanning
      calorimetry (DSC), and powder X-ray diffraction (PXRD), respectively. The drug
      loading and encapsulation efficiency were determined by UV spectrophotometry. The
      results showed that the prepared dacarbazine-loaded cubosomes had mean diameters
      ranging from 86 to 106 nm. In addition to the TEM, the characteristic peaks from
      PXRD data suggested that the freeze-dried nanoformulations were indeed cubic in
      nature. DSC and PXRD analysis suggested the 0.06 or 0.28% w/w actual drug loaded
      inside cubosomes was in the amorphous or molecular state. These physicochemical
      characteristics would affect the nanoformulation shelf-life, efficacy, and
      safety.

PMID- 20694535
TI  - Pilon fractures.

PMID- 20694536
TI  - Application of the Ilizarov technique to the correction of neurologic
      equinocavovarus foot deformity.
AB  - BACKGROUND: The treatment of rigid equinocavovarus foot deformities caused by
      neurologic disorders is often difficult and relapse is common.
      QUESTIONS/PURPOSES: We asked whether the Ilizarov technique could be used for
      correction of neurologic equinocavovarus foot deformities resulting in improved
      foot and ankle function and patient satisfaction. PATIENTS AND METHODS: The
      neurologic equinocavovarus foot deformities of 26 patients (mean age, 18.7 years;
      29 feet) were treated using the Ilizarov technique. Nine feet were treated by
      distraction histiogenesis only with limited soft tissue release, whereas 20 feet
      needed additional osteotomy and/or tendon transfer/lengthening. Minimum followup
      was 12 months (mean, 72.9 months; range, 12-155 months). RESULTS: The mean time
      required for deformity correction was 27.1 days (range, 14-47 days) and the mean
      time for stabilization in the apparatus was 23.2 days (range, 7-53 days). A
      painless, stable, and plantigrade result was obtained by 22 patients (24 feet).
      Mild residual foot deformity was observed in the remaining five feet of four
      patients. Six patients (six feet) experienced postoperative complications. Three
      patients (four feet) experienced recurrence of the deformity requiring surgical
      correction. CONCLUSIONS: Ilizarov soft tissue distraction with or without
      callotasis of tarsal bone(s) allows a greater degree of correction of neurologic
      equinocavovarus foot deformities. However, to reduce the risk of recurrence after
      fixator removal, it may be necessary to overcorrect the deformity while in the
      fixator, to use nighttime splinting, and most importantly, to eliminate
      neuromuscular imbalance, if necessary, by combining arthrodesis with or without
      tendon transfer. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines
      for Authors for a complete description of levels of evidence.

PMID- 20694537
TI  - Hospital economics of primary total knee arthroplasty at a teaching hospital.
AB  - BACKGROUND: The hospital cost of total knee arthroplasty (TKA) in the United
      States is a major growing expense for the Centers for Medicare & Medicaid
      Services (CMS). Many hospitals are unable to deliver TKA with profitable or
      breakeven economics under the current Diagnosis-Related Group (DRG) hospital
      reimbursement system. QUESTIONS/PURPOSES: The purposes of the current study were
      to (1) determine revenue, expenses, and profitability (loss) for TKA for all
      patients and for different payors; (2) define changes in utilization and unit
      costs associated with this operation; and (3) describe TKA cost control
      strategies to provide insight for hospitals to improve their economic results for
      TKA. RESULTS: From 1991 to 2009, Lahey Clinic converted a $2172 loss per case on
      primary TKA in 1991 to a $2986 profit per case in 2008. The improved economics
      was associated with decreasing revenue in inflation-adjusted dollars and
      implementation of hospital cost control programs that reduced hospital expenses
      for TKA. Reduction of hospital length of stay and reduction of knee implant costs
      were the major drivers of hospital expense reduction. CONCLUSIONS: During the
      last 25 years, our economic experience with TKA is concerning. Hospital revenues
      have lagged behind inflation, hospital expenses have been reduced, and our
      institution is earning a profit. However, the margin for TKA is decreasing and
      Managed Medicare patients do not generate a profit. The erosion of hospital
      revenue for TKA will become a critical issue if it leads to economic losses for
      hospitals or reduced access to TKA. LEVEL OF EVIDENCE: Level III, Economic and
      Decision Analyses. See Guidelines for Authors for a complete description of
      levels of evidence.

PMID- 20694538
TI  - Acute exercise activates myocardial nuclear factor kappa B.
AB  - The myocardial stress response to exercise is dependent on exercise intensity and
      thus understanding the molecular responses between various exercise intensity
      levels might aid in exercise prescription. Nuclear factor kappa B (NF-kappaB) is
      a ubiquitous transcription factor that mediates a variety of cellular processes
      including inflammation, immune responses, apoptosis and cell growth/development.
      NF-kappaB can be comprised of homo- and/or heterodimers formed from five distinct
      proteins: p50 (NF-kappaB1), p52 (NF-kappaB2), RelA (p65), c-Rel, and RelB. NF
      kappaB is located in the cytoplasm and kept inactive by inhibitory proteins but
      following the exposure to a myriad of stimuli, an activated NF-kappaB dimer
      translocates to the nucleus and exerts transcriptional effects on upwards of 150
      genes. To examine the activation of NF-kappaB in the myocardium following
      exercise, male Sprague-Dawley rats (n = 24) were exercised by treadmill running
      at 20 m/min for 30 min or 30 m/min for 20 min. At 0, 2, or 24 h following
      exercise, animals were anesthetized, hearts excised and immediately frozen in
      liquid nitrogen. Portions of hearts were homogenized, protein concentrations
      determined and extracts assayed for NF-kappaB activation (DNA binding activity)
      using electrophoretic mobility shift assays (EMSA). Visual examination of EMSA
      autoradiographs revealed an enhanced NF-kappaB activation in the hearts from
      exercised animals when compared with non-running controls. Subsequent supershift
      analyses using antibodies specific for NF-kappaB subunits showed the higher
      intensity exercise was associated with p65 (RelA) in the activated NF-kappaB
      complex while the NF-kappaB complex in hearts from animals exercised at the lower
      intensity was comprised primarily of p50. These data suggest exercise is capable
      of activating myocardial NF-kappaB and that a threshold for the activation of
      specific NF-kappaB subunits may exist.

PMID- 20694539
TI  - Purinergic modulation of granule cells.
AB  - Extracellular purines exert their action in the nervous system through purinergic
      neurotransmission and neuromodulatory processes. Among brain areas, efforts have
      been made to investigate the purinergic modulation of the cerebellar cortex. In
      addition, the use of granule cells in culture as a neuronal in vitro model
      provided important information about the implications of purines in mechanisms
      such as cell survival and differentiation. This short review is focused on the
      function of purines in the physiology of granule cells in situ and in vitro. In
      situ, adenosine has been shown to inhibit some of the glutamatergic and GABAergic
      synaptic inputs to granule cells. The inhibition of GABA input allows an increase
      in the excitability of the cell while the output (parallel fibers) of granule
      cells is also down-regulated by adenosine, suggesting a complex mode of
      regulation by purines. In vitro, granule cells have been shown to express members
      of all classes of purinergic receptors, P2X (ionotropic), P2Y (metabotropic) and
      adenosine receptors. The specific expression of these receptors and the
      downstream signaling pathways coupling them to cell survival and growth have been
      extensively studied.

PMID- 20694540
TI  - Vasoactive intestinal polypeptide relaxes isolated rat pulmonary artery rings
      through two distinct mechanisms.
AB  - Vasoactive intestinal polypeptide (VIP), an endogenous neuropeptide normally
      present in lungs and other organs, relaxes pulmonary arteries (PAs) in different
      species, whereas the underlying mechanisms are still not fully understood. The
      aim of this study, therefore, is to investigate the signal transduction of VIP in
      the relaxation of isolated rat PA rings. The isometric tension of the rings was
      studied in vitro with force-electricity transducers. In endothelium-intact (EI)
      rings, VIP elicited concentration-dependent relaxation after the rings were pre
      contracted by phenylephrine. A similar effect, though smaller, was observed in
      endothelium-denuded (ED) rings. Inhibition of the endothelial nitric oxide
      synthase (eNOS) by NG-nitro-L-arginine methyl ester diminished the VIP-induced
      vasodilatation of PA rings. The VIP-induced vasorelaxation was markedly reduced
      by the inhibition of the phosphatidylinositol 3-kinase/protein kinase B
      (PI3K/Akt) signaling pathway with wortmannin and LY294002, respectively, which
      was seen in EI rings, but not in ED rings. Western blot analysis revealed that
      VIP increased the phosphorylation of eNOS at Ser 1177, but did not affect the
      overall expression of eNOS. In ED rings, the PKA inhibitor H-89 and K(ATP)
      channel inhibitor glibenclamide almost totally abolished the vasodilatation
      effect of VIP. The results suggested that the vasodilatation effect of VIP on rat
      PAs is mediated by both vascular endothelium and smooth muscle, involving
      respectively the PI3K/Akt-eNOS pathway and the PKA-K(ATP) channel pathway.

PMID- 20694541
TI  - Anal sphincter repair for fecal incontinence: experience from a tertiary care
      centre.
AB  - AIM: Structural anal sphincter damage may be secondary to obstetric anal
      sphincter injury, perineal trauma or anorectal surgery. We reviewed the spectrum
      of anal sphincter injuries and their outcomes in a tertiary care colorectal unit.
      METHODS: Data of patients who underwent anal sphincter repair between 2004 and
      2008 were analyzed retrospectively. Outcomes were compared with respect to
      etiology, type of repair, previous attempts at repair and manometry findings.
      Outcomes were defined as good or poor based on patient satisfaction as the
      primary criteria. RESULTS: Thirty-four patients underwent anal sphincter repair.
      Twenty-two injuries were obstetric, eight traumatic, and four iatrogenic. All
      patients underwent overlap sphincteroplasty with six additional anterior
      levatorplasty and seven graciloplasty. Twenty-three (67.6%) patients had a good
      outcome while nine (26.4%) had a poor outcome. All patients who had augmentation
      anterior levatorplasty had a good outcome. Fifty percent of patients with a
      previous sphincter repair and 42.9% requiring augmentation graciloplasty had a
      poor outcome. Median resting and squeeze anal pressures increased from 57.5 to 70
      cmH2O and 90.25 to 111 cmH2O in those with a good outcome. CONCLUSIONS: Overlap
      sphincteroplasty has a good outcome in majority of the patients with incontinence
      due to a structural sphincter defect. Additional anterior levatorplasty may
      improve outcomes. Previous failed repairs or use of a gracilis muscle
      augmentation may have a worse outcome secondary to poor native sphincter muscle.
      Improvement in resting and squeeze pressures on anal manometry may be associated
      with a good outcome.

PMID- 20694543
TI  - [Oncological follow-up].

PMID- 20694542
TI  - Influence of nitric oxide synthase inhibition on vasopressin and corticosterone
      secretion during water deprivation in rats.
AB  - Nitric oxide (NO) is a short-lived radical that functions as a neurotransmitter
      in the central nervous system and plays a physiological role in the regulation of
      hypothalamic-pituitary-adrenal axis and vasopressinergic axis. In the present
      study, we aimed to investigate the interaction between the generation of NO and
      vasopressin (AVP) and corticosterone release after 3 days of water deprivation in
      rats. Animals were previously treated with intraperitoneal (i.p.) saline or L
      nitro-arginine methyl ester (L-NAME) injection. L-NAME is a nonspecific inhibitor
      of nitric oxide synthases. In control rats given i.p. saline or L-NAME,
      hypothalamic, pituitary, and plasma AVP levels and plasma corticosterone did not
      change from baseline levels (p>0.05). Three days of water deprivation increased
      significantly the corticosterone levels in plasma (p<0.01) and AVP levels in
      hypothalamus and plasma (p<0.01), but not in pituitary, which showed a
      significant decrease. These variations were concomitant with the elevation of
      nitrates/nitrates in plasma. L-NAME injection abolished significantly (p<0.01)
      the elevation of plasma corticosterone and hypothalamic AVP levels induced by
      water deprivation. These findings showed that in water-deprived rats, nitric
      oxide synthase inhibition by L-NAME inhibits corticosterone and vasopressin
      release, suggesting a potent stimulatory role of NO.

PMID- 20694544
TI  - [Patients with malignancies of the oro- and hypopharynx as well as the larynx.
      Significance/importance of oncological aftercare consultation].
AB  - The necessity of a long-time, closely monitored, well-structured, personal and
      time-consuming aftercare consultation is still discussed controversially. Based
      on the analysis of our oncological patients with tumours of the pharynx and
      larynx in the period from 1999-2000 we want to emphasize that after treatment is
      of vital importance. Besides the main focus of oncology on the early detection of
      recurrent tumours, distant metastases and second primary tumours as well as a
      fast interdisciplinary and mostly multimodal treatment planning, consultation is
      also a central point of reference and coordination site for rehabilitation,
      psycho-oncology and quality assurance of treatment. Last but not least
      consultation serves for purposes of continuous data collection and oncological
      epidemiology.

PMID- 20694545
TI  - [Prophylaxis of venous thromboembolism and anticoagulation bridging. Strategies
      in otorhinolaryngology].
AB  - Various interdisciplinary guidelines recommend that in-patients at risk of venous
      thromboembolism should receive pharmacologic prophylaxis. Among the
      anticoagulants low-molecular-weight heparins (LMWH) and fondaparinux can be
      considered the medications of choice because of the favorable pharmacokinetic
      properties when compared with unfractionated heparin. Treatment with vitamin K
      antagonists has to be interrupted in patients undergoing major surgery or
      invasive procedures. Oral anticoagulation has to be temporarily replaced by short
      acting anticoagulants such as LMWH in order to prevent thromboembolic
      complications (anticoagulation bridging). Although LMWHs have not been approved
      for this clinical setting their efficacy and safety has been demonstrated in
      several recent studies. Detailed recommendations for prophylaxis of venous
      thromboembolism in otorhinolaryngology are lacking although numerous surgical
      procedures are considered to be associated with a significant risk of
      thromboembolism. A strategy for pharmacologic prophylaxis of venous
      thromboembolism and anticoagulation bridging in otorhinolaryngology is proposed.

PMID- 20694546
TI  - [Unilateral neck mass, dysphagia and dyspnea].
AB  - Extraocular sebaceous carcinoma is a rare malignant tumor, arising from skin and
      salivary glands. An important differential diagnosis in the head and neck region
      is metastasizing squamous cell carcinoma. Using case histories, the clinical and
      histological findings as well as the therapeutic principles of this entity are
      described. Only a few cases of this malignancy in the ENT area are published in
      the literature.

PMID- 20694548
TI  - [Not Available].

PMID- 20694547
TI  - [Rare mechanisms of blowout fractures. Discussion of two case reports].
AB  - In the emergency room different forms of traumata with resulting insulating
      orbital blowout fracture are observed. The cause of accident is almost always
      impact to the central face with a solid object or on a hard surface. The
      hydraulic pressure theory and buckling force theory in terms of the
      pathomechanism are valid and accepted explanation models. We report two clinical
      cases of unusual injury mechanisms, which we discuss with reference to the
      available literature.

PMID- 20694549
TI  - [Not Available].

PMID- 20694551
TI  - [Not Available].

PMID- 20694550
TI  - [Not Available].

PMID- 20694552
TI  - Summaries of articles.

PMID- 20694553
TI  - Erratum to: Emergences de la philosophie au Moyen Age.

PMID- 20694554
TI  - Levamisole-induced reduction in seizure threshold: a possible role of nicotinic
      acetylcholine receptor-mediated pathway.
AB  - Levamisole produces seizures in man and is also known to activate the neuronal
      nicotinic acetylcholine receptors, which are further known to elicit seizure
      activity. Therefore, the present study has been designed to investigate the role
      of nicotinic acetylcholine receptor activation in the seizure-inducing effect of
      levamisole. Levamisole, at the doses of 5, 10 and 20 mg kg(-1), i.p. were used to
      elicit seizures in mice. Seizures were assessed in terms of the onset time of
      Straub's tail phenomenon, jerky movements of whole body and convulsions.
      Additionally, an isobolographic design was used to examine the interaction of
      systemically administered levamisole and nicotine. Prior administration of 2, 2,
      6, 6-tetramethylpiperidin-4-yl heptanoate (TMPH), a selective inhibitor of
      neuronal nicotinic acetylcholine receptors, markedly attenuated the seizure
      inducing effect of levamisole. Moreover, administration of TMPH per se did not
      produce any behavioural changes in mice. Furthermore, nicotine was observed exert
      a synergistic interaction with levamisole. Therefore, it may be suggested that
      levamisole-induced reduction in seizure threshold might be ascribed to the
      activation of a neuronal nicotinic acetylcholine receptor activation-linked
      mechanism.

PMID- 20694555
TI  - Impact of obstructive sleep apnea on global myocardial performance in children
      assessed by tissue Doppler imaging.
AB  - This study aimed to assess the impact of obstructive sleep apnea (OSA) due to
      adenotonsillar hypertrophy (ATH) on the global myocardial performance in children
      using tissue Doppler imaging (TDI) and to evaluate the reversibility of the
      disorder after adenotonsillectomy (AT). The study included 42 children with OSA
      due to ATH (mean age, 5 +/- 3.14 years) as the study group and 45 age- and sex
      matched healthy children (mean age, 5.2 +/- 3.08 years) as the control group.
      Polysomnography and echocardiography were performed. Indexed left ventricular
      mass (LVMi), pulmonary artery systolic pressure, mean pulmonary artery pressure
      (mPAP), and pulmonary vascular resistance (PVR) were calculated by
      echocardiography. Tissue Doppler imaging was used to determine the left
      ventricular and right ventricular myocardial performance index (MPI) of patients
      and control subjects before and after AT. The patients were classified into mild
      OSA (apnea-hypopnea index [AHI] 1-5; n = 18)] and moderate to severe OSA (AHI >5;
      n = 24) according to polysomnography findings. All the children in the control
      group had an AHI less than 1. They were treated using AT, then reevaluated by
      polysomnography and echocardiographic examination 6 to 8 months after surgery.
      Results are described as mean +/- standard deviation. The patients with OSA had
      higher pulmonary artery systolic pressure, mPAP, PVR, LVMi, and right ventricular
      diastolic diameter than the control subjects. The patients with moderate to
      severe OSA showed more prominent changes than the patients with mild OSA, but the
      latter still differed significantly from the control subjects. The TDI-derived
      right ventricular MPI and left ventricular MPI measurements of the patients with
      OSA were higher (mean, 0.40 +/- 0.08 vs 0.28 +/- 0.01; p < 0.001) than those of
      the control subjects and (0.45 +/- 0.05 vs 0.32 +/- 0.05; p < 0.001) and
      correlated well with AHI and mPAP. In addition, mPAP was significantly correlated
      with AHI. Postoperatively, relief of OSA was validated by polysomnography, and a
      repeat of the echocardiographic parameters showed no significant differences
      between the patients and the control subjects. Tissue Doppler imaging can detect
      the subtle, subclinical changes in cardiac performance that occur in OSA due to
      adenotonsillar hypertrophy. Such changes generally are reversible after surgical
      treatment.

PMID- 20694556
TI  - Germinable soil seed banks and the restoration potential of abandoned cropland on
      the Chinese hilly-gullied loess plateau.
AB  - Poor vegetation cover is generally considered to be a major factor causing soil
      erosion on the Loess Plateau in China. It has been argued that tree planting
      restoration is ineffective, and natural re-vegetation is an alternative
      ecological solution for restoring abandoned cropland and controlling soil
      erosion. The aims of this study were to investigate the characteristics of soil
      seed banks and to assess the natural restoration potential of abandoned cropland
      in the hilly-gullied Loess Plateau. The soil seed bank was identified by the
      germination method with the soil samples, which were collected at four sampling
      times (April, August, and October 2005 and August 2006) from 12 plots abandoned 3
      30 years prior to sampling. The seed bank densities of all of the samples in the
      0-10 cm soil layer varied from 1,067 +/- 225 to 14,967 +/- 1,606 seeds m(-2).
      Fifty-one species (24 annual and 27 perennial species) belonging to 18 families
      were identified, and 39% of these species belonged to the families Compositae and
      Gramineae. The pioneer species Artemisia scoparia dominated the seed bank, with
      an average seed density of 3,722 seeds m(-2), and accounted for 74.4% of the
      seeds in the bank. The local dominant species (such as Lespedeza davurica,
      Artemisia gmelinii, Bothriochloa ischaemun and Stipa bungeana) of the later
      succession stages also existed at densities varying from 17 to 1, 383 seeds m(
      2). The combination of soil seed bank characteristics, reproductive traits of the
      species, the specific landscape conditions indicates that the potential to
      restoring the abandoned croplands in the hilly-gullied Loess Plateau via natural
      re-vegetation could be substantial.

PMID- 20694557
TI  - Endoscopic third ventriculostomy for hydrocephalus in children younger than 1
      year of age.
AB  - OBJECTIVE: The purpose of this study is to assess the role of endoscopic third
      ventriculostomy (ETV) in the treatment of hydrocephalus in children under 1 year
      of age. The authors analyzed data of ETV in their institution. METHODS: Between
      January 1995 and December 2008, 52 ETV procedures were performed for the
      treatment of hydrocephalus in 49 infants (32 male and 17 female). Their age
      ranged from 6 days to just under 12 months (mean age 6.2 months). The cause of
      hydrocephalus was occlusive in 43 patients (aqueduct stenosis in 31, Chiari II
      malformation in eight, Dandy-Walker cyst in two, quadrigeminal lipoma in one, and
      cerebellopontine angle arachnoid cyst in one patient). Communicating
      hydrocephalus was caused by intraventricular hemorrhage, meningitis, and/or
      ventriculitis in six patients. RESULTS: The overall success rate was 69.4% with
      mean follow-up period of 68.2 months. Patients with aqueduct stenosis had a
      higher success rate of ETV which was 77.4%. Seven infants were born preterm, six
      of them required a permanent ventriculoperitoneal shunts (VPS; P = 0.003).
      Malfunctioned VPS was removed in two patients following ETV. There was one death
      from intracranial hemorrhage, two cerebrospinal fluid leaks, and one meningitis.
      CONCLUSION: Endoscopic third ventriculostomy can be considered a possible
      treatment procedure alternative to VPS for the treatment of occlusive
      hydrocephalus in infants. ETV was effective in full-term infants while the
      results in low birth weight, preterm infants were poor. Success of ETV is not
      only age dependent but also etiology dependent. Infants with occlusive
      hydrocephalus treated with VPS, who present with shunt failure, could be treated
      by ETV and removal of the shunt device.

PMID- 20694558
TI  - ASPM gene expression in medulloblastoma.
AB  - PURPOSE: Medulloblastomas are the most common malignant tumors of the central
      nervous system in childhood. The incidence is about 19-20% between children
      younger than 16 years old with peak incidence between 4 and 7 years. Despite its
      sensibility to no specific therapeutic means like chemotherapy and radiotherapy,
      the treatment is very aggressive and frequently results in regression, growth
      deficit, and endocrine dysfunction. From this point of view, new treatment
      approaches are needed such as molecular targeted therapies. Studies in
      glioblastoma demonstrated that ASPM gene was overexpressed when compared to
      normal brain and ASPM inhibition by siRNA-mediated inhibits tumor cell
      proliferation and neural stem cell proliferation, supporting ASPM gene as a
      potential molecular target in glioblastoma. The aim of this work was to evaluate
      ASPM expression in medulloblastoma fragment samples, and to compare the results
      with the patient clinical features. METHODS: Analysis of gene expression was
      performed by quantitative PCR real time using SYBR Green system in tumor samples
      from 37 children. The t test was used to analyze the gene expression, and Mann
      Whitney test was performed to analyze the relationship between gene expressions
      and clinical characteristics. Kaplan-Meier test evaluated curve survival.
      RESULTS: All samples overexpressed ASPM gene more than 40-fold. However, we did
      not find any association between the overexpressed samples and the clinical
      parameters. CONCLUSION: ASPM overexpression may modify the ability of stem cells
      to differentiate during the development of the central nervous system,
      contributing to the development of medulloblastoma, a tumor of embryonic origin
      from cerebellar progenitor cells.

PMID- 20694560
TI  - Common genetic polymorphisms in moyamoya and atherosclerotic disease in
      Europeans.
AB  - PURPOSE: Moyamoya is the most common cerebrovascular disease in children in
      Japan. The disease's etiology is still widely unknown. Several publications
      describe histopathological changes in the walls of affected vessels similar to
      those seen in atherosclerosis. In this study, we analyzed the DNA of European
      patients with Moyamoya disease for single nucleotide polymorphisms associated
      with atherosclerotic changes. METHODS: We genotyped 17 SNPs in or adjacent to 11
      genes (ELN, LIMK1, CDKN2A/B, CXCL12, Pseudogene ENSG00000197218, PSRC1, MTHFD1L,
      SMAD3, MIA3, PDGF-B, TIMP2) comparing 40 DNA samples of Moyamoya disease patients
      to 68 healthy controls from central Europe. The mean age of onset of Moyamoya
      disease (MMD)-related symptoms was 15.4 years of age. Genotyping was performed by
      sequencing the SNP containing genetic regions with custom-made primers. RESULTS:
      We found strong association of one SNP (rs599839 [A/G], OR = 2.17, 95% CI = 1.17,
      4.05; p = 0.01) with the risk allele G located in the 3' UTR region of the PSRC-1
      gene. Three further SNPs (rs8326, rs34208922, rs501120) in or adjacent to the
      genes ELN and CXCL12 showed tendencies towards risk alleles with p values between
      0.1 and 0.2 but did not reach statistical significance in our cohort.
      CONCLUSIONS: Our results indicate a possible parallel of common processes in the
      genesis of Moyamoya disease and atherosclerotic disease. Further analyses in
      larger European cohorts and replication in patients of different ethnicity may
      lead to possible early detection of patients at risk for developing MMD and
      subsequently to future causative therapies.

PMID- 20694561
TI  - Control theoretic interpretation of directional motion preferences in optic flow
      processing interneurons.
AB  - In this article, we formalize the processing of optic flow in identified fly
      lobula plate tangential cells and develop a control theoretic framework that
      suggests how the signals of these cells may be combined and used to achieve
      reflex-like navigation behavior. We show that this feedback gain synthesis task
      can be cast as a combined static state estimation and linear feedback control
      problem. Our framework allows us to analyze and determine the relationship
      between optic flow measurements and actuator commands, which greatly simplifies
      the implementation of biologically inspired control architectures on terrestrial
      and aerial robotic platforms.

PMID- 20694562
TI  - Silymarin treatment reduces granuloma and hepatic fibrosis in experimental
      schistosomiasis.
AB  - The schistosomiasis is a parasitic infection with relevant social impact and an
      important health problem in many countries around world. The pathology of this
      infection is characterized by a granulomatous reaction around parasite eggs and
      by hepatic fibrosis. Silymarin, a complex compound isolated from Silybum marianum
      (L.) Gaertner, have been described as hepatoprotective, antioxidant,
      antifibrotic, immunomodulator, and anti-neoplastic agent. Some of these
      capacities could potentially protect against pathology in schistosomiasis.
      Herein, we evaluated the effects of silymarin on parasite burden, granuloma
      sizes, and liver fibrosis, which are associated with severity and morbidity of
      this disease. BALB/c mice treated intraperitoneally with 10, 20, or 25 doses of
      silymarin (10 mg kg(-1)) suspended in carboxymethylcellulose were analyzed at 55
      days post-infection. Silymarin (1) did not affect parasite oviposition capacity;
      (2) reduced granulomatous peri-ovular reaction in the liver, and (3) decreased
      hepatic fibrosis in this infection. Taken together, these data suggest that
      treatment with silymarin at acute phase of schistosomiasis may result in a mild
      course of murine schistosomiasis and can be a promising complementary treatment
      reverting sequelae of this infection.

PMID- 20694563
TI  - Genetic variability of Anisakis simplex s.s. parasitizing European hake
      (Merluccius merluccius) in the Little Sole Bank area in the Northeast Atlantic.
AB  - In this study, we researched the presence of anisakids in specimens of Merluccius
      merluccius caught in the area of Little Sole Bank, in the Northeast Atlantic, and
      found that 100% of the European hake examined were infected and showed high
      average values of abundance (976.88) and intensity (976.88). The larvae were
      identified in morphological terms as morphotype type I and in molecular terms as
      Anisakis simplex s.s via polymerase chain reaction (PCR) restriction fragment
      length polymorphism of the rDNA. The genetic variability of the A. simplex s.s
      population in the North Atlantic is notable, with at least two ribosomal and
      three mitochondrial haplotypes which are different from the specimen used as
      control, reflecting the diversity of this species, an aspect which has scarcely
      been studied to date. The cox-2 gene appears to be an interesting candidate for
      generating new genetic markers which can be applied to differentiate between A.
      simplex s.s and Anisakis pegreffii. We detected 11 fixed differences in this
      gene, and it also offers the advantage of being easily amplified by PCR. The high
      prevalence of infection by A. simplex s.s and the extremely high average
      intensity and abundance values can have significant repercussions on public
      health, especially among populations which regularly eat insufficiently cooked or
      raw fish and have a certain genetic predisposition; the genetic variability of
      the parasite could be another factor to take into account.

PMID- 20694564
TI  - Toxicity and quality of life outcomes in ovarian cancer patients participating in
      randomized controlled trials.
AB  - MAIN PURPOSE: The objective of this study was to determine the relationship
      between clinician-graded symptoms based on the common toxicity criteria (CTC) and
      patient-reported quality of life (QoL). We hypothesized that toxicity symptoms
      that are objective or observable would have a higher correlation with QoL than
      subjective data. MATERIAL AND METHODS: A retrospective analyses of data from
      three closed randomized chemotherapy trials was performed. A total of 2,110
      patients with ovarian cancer (stage IIB-IV) who had complete toxicity and QoL
      data at cycles 3 and 6 were included. Toxicities were graded according to the
      National Cancer Institute Common Toxicity Criteria. Quality of life was assessed
      every other cycle by using the European Organization for Research and Treatment
      of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). MAIN RESULTS:
      Correlations between CTC grading and the QLQ-C30 functioning scales were weak
      (<0.30); correlation coefficients between CTC ratings and the QLQ-C30 symptom
      scales including nausea, vomiting, constipation, pain, and dyspnea ranged from
      0.32 to 0.49 except for constipation (0.55). On a symptom level exact agreement
      between clinician and patient reporting ranged from 54.2% (pain) to 80.8%
      (emesis/vomiting). When symptom grading differed, patients reported greater
      severity for pain, constipation, and dyspnea, whereas clinicians graded
      emesis/vomiting and nausea as more severe than the grading by patients.
      CONCLUSION: Patient experience is not routinely captured by CTC toxicity scales.
      Therefore, clinicians should not entirely rely on the CTC grading but consider
      patient-reported outcomes as well.

PMID- 20694566
TI  - The complete genome sequence of the BD variant of grapevine leafroll-associated
      virus 2.

PMID- 20694565
TI  - What to eat when off treatment and living with involuntary weight loss and
      cancer: a systematic search and narrative review.
AB  - PURPOSE: The aim of this study was to report a systematic search and narrative
      review of the evidence base that can inform dietary advice for patients off
      treatment living with cancer cachexia syndrome (CCS). METHODS: Searches were
      conducted in MEDLINE, EMBASE, PsycINFO and CINAHL databases for publications
      about diet and cancer patients off treatment with symptoms of CCS. The following
      limits were applied: English language, from September 1998 to September 2008 and
      adults. In addition, a hand search included the reference lists of papers
      identified. Seven hundred and eighteen abstracts were assessed against
      inclusion/exclusion criteria and 88 were selected for full text independent
      examination by two researchers. Information from 48 papers was extracted, quality
      assessed, thematically analyzed and presented as a narrative synthesis. RESULTS:
      Two dominant perspectives emerged on what should be eaten by weight-losing cancer
      patients. The majority of authors advocated a nutrient-dense diet, facilitated by
      nutritional counselling. The alternative approach was to advise the patient to
      'eat what they want'. There is little robust evidence to justify either approach
      as able to deliver on the range of physical and psychosocial objectives that they
      aim to achieve. CONCLUSION: A new model for the delivery of nutritional care may
      benefit cancer patients (off treatment) living with weight loss. The proposed
      model integrates the two identified perspectives to facilitate optimal food
      intake taking into account the patient's (1) disease symptoms and treatment side
      effects (2) emotional adaptation to illness and (3) social circumstances.
      Research is needed to establish which of these obstacles to eating can be changed
      for which patient groups to improve patient outcomes.

PMID- 20694567
TI  - Influence of ultrasound application on inlays luting with self-adhesive resin
      cements.
AB  - The study was aimed at assessing the influence of the cement manipulation and
      ultrasounds application on the bonding potential of self-adhesive resin cements
      to dentin by microtensile bond strength testing and microscopic observations of
      the interface. Fifty-six standardized mesio-occlusal class II cavities were
      prepared in extracted third molars. Class II inlays were made using the nano
      hybrid resin composite Gradia Forte (GC Corp, Tokyo, Japan), following the
      manufacturer's instruction. The sample was randomly divided into two groups (n =
      28) according to the luting technique. Half of the specimens were luted under a
      static seating pressure (P), while the other ones were cemented under vibration
      (V). The inlays were luted using the following self-adhesive resin cements: G-Cem
      (G, GC Corp., Tokyo, Japan) Automix (GA) and Capsule (GC); RelyX Unicem (RU, 3 M
      ESPE, Seefeld, Germany) Clicker (RUC) and Aplicap (RUA). Microtensile sticks and
      specimens for scanning electron microscope (SEM) observations were obtained from
      the luted teeth. The interfacial strengths measured for the cements under static
      pressure or ultrasonic vibration were [median (interquartile range)]: GC/V 4 (2.3
      7.9); GC/P 6.8 (4.1-10.1); GA/V 3 (1.9-6.7); GA/P 1.9 (0-5.1); RUC/V 6.6 (4.6
      9.8); RUC/P 4.1 (1.8-6.4); RUA/V 6.2 (2.4-10.4); RUA/P 3.4 (0-5.4). The cement
      formulation influenced dentin bond strength of G. RU bond strength was affected
      by the luting technique. SEM analysis revealed a homogeneous structure and
      reduced porosities for both cements as a result of ultrasonic vibration. RU
      benefited from the application of ultrasounds, while GC achieved higher bond
      strengths than GA.

PMID- 20694568
TI  - Accuracy of low-dose chest CT in intensive care patients.
AB  - In this prospective study, we set out to determine the accuracy of low-dose
      computerized tomography (LDCT) of the chest in intensive care patients. Fifteen
      adult intensive care patients were examined with a standard-dose CT protocol
      (average radiation dose = 6.7 mSv), chosen as the reference standard, followed by
      a non-contrast-enhanced LDCT protocol (average radiation dose = 0.59 mSv). Each
      examination was then read by two separate groups of radiologists blinded to both
      the purpose and the protocol of the study. In the small group examined, the
      results showed 100% accuracy in the diagnosis of pneumomediastinum, pericardial
      effusion, and pleural effusion, and 90% accuracy in the diagnosis of pneumothorax
      and consolidation. There were no false-positive findings, and the few false
      negative findings were unlikely to lead to any clinical interventions. Our
      examination protocol, while providing a tenfold reduction of the radiation dose,
      nevertheless remained accurate enough for resolving certain clinical questions
      common in the intensive care patient. Thus, we suggest that protocols aimed at
      reducing the radiation dose in chest CT could be applied to the intensive care
      patient for resolving some specific questions, without compromising the
      diagnostic yield of the examinations.

PMID- 20694569
TI  - Anti-inflammatory and antimicrobial effects of nanocatechin in a chronic
      bacterial prostatitis rat model.
AB  - Chronic bacterial prostatitis (CBP) is one of the most common relapsing urinary
      tract infection (UTI) in males. Catechin, an extract of green tea, is known to
      have anti-inflammatory and antimicrobial effects against various bacteria.
      However, catechin can be easily degenerated during digestion, and this may result
      in decreased absorption into the body. Nanocatechin is catechin coated with
      hydroxypropyl methyl cellulose by nanotechnology. It reduces degeneration during
      digestion and enhances absorption of catechin into the body. We evaluated the
      anti-inflammatory and antimicrobial effect of nanocatechin on CBP and also
      analyzed plasma concentration of catechins to evaluate absorptivity in an animal
      model. Forty rats demonstrating CBP were randomly divided into four groups:
      control, ciprofloxacin, catechin, and nanocatechin. After treatment, the results
      of microbiological culture of prostate and urine samples as well as histological
      findings of the prostate in each group were analyzed. Plasma concentration of
      catechins in catechin and nanocatechin groups was compared. The use of
      ciprofloxacin, catechin, and nanocatechin showed statistically significant
      decrease in bacterial growth and improvement in prostatic inflammation compared
      with the control group. The nanocatechin group showed statistically significant
      decrease in bacterial growth and improvement in prostatic inflammation compared
      with the catechin group. Plasma concentrations of epicatechin, gallocatechin
      gallate, and epigallocatechin gallate were significantly higher in the
      nanocatechin group than those in the catechin group. These results suggest that
      nanocatechin has better antimicrobial and anti-inflammatory effects on rat CBP
      than catechin due to higher absorption into the body.

PMID- 20694570
TI  - Antimicrobial-susceptible patterns of Staphylococcus aureus isolated from
      surgical infections: a new approach.
AB  - Our goal was to analyze minimum inhibitory concentration (MIC) data for
      Staphylococcus aureus isolated from surgical infections (SIs) and to look for
      correlations among the clinically available antimicrobials that were tested.
      Clinical isolates from SIs were collected by a multicenter surveillance group
      involving 34 institutions in Japan. During the period April 1998 to March 2007,
      312 strains of S. aureus [71 methicillin susceptible (MSSA) and 241 methicillin
      resistant (MRSA)] were consecutively obtained from these institutions. MIC data
      for 18 clinically available antimicrobial agents [ABPC, CEZ, CTM, CMX, CPR, FMOX,
      CFPM, CZOP, IPM, MEMP, GM, ABK, MINO, CLDM, FOM, LVFX, VCM, and TEIC
      (abbreviations defined in Tables 2 and 3)] against these isolates was analyzed
      using a principal component analysis (PCA). PCA revealed that four principal
      components explained 71.1% of the total variance. The first component consisted
      of major contributions from MEPM and IPM. The second component consisted of major
      contributions from MINO. These two-first axes, which were strong and explained
      54.2% of the total variance, were able to classify the clinical isolates into
      four clusters. Furthermore, the proportion of the four clusters provided the
      characteristics of the S. aureus that were clinically isolated at each institute.
      PCA is a clinically applicable method for analyzing MIC patterns. Such analyses
      might contribute to the establishment of a practical classification of
      antimicrobial agents and to the identification of the characteristic
      antimicrobial resistance patterns at each institute.

PMID- 20694571
TI  - Clinical effects of 2 days of treatment by fosfomycin calcium for acute
      uncomplicated cystitis in women.
AB  - Fosfomycin calcium is a fosfomycin antimicrobial agent with a characteristic
      structure. After oral administration, the drug is absorbed and excreted via the
      kidneys in the unchanged form, without being metabolized in the body. It is,
      therefore, indicated for the treatment of urinary tract diseases, including
      cystitis and pyelonephritis. In the present study, the clinical usefulness of
      fosfomycin calcium (FOSMICIN(r) TABLETS 500) administered orally at the dosage of
      1 g (two tablets) three times daily for 2 days was examined in female patients,
      who were at least 20 years of age, with acute uncomplicated cystitis of bacterial
      origin. Of the 48 patients enrolled between February 2008 and August 2008, 39
      were evaluable for efficacy and safety. Overall evaluation of the cure revealed
      that microbiological eradication rate (microbiological outcome) and clinical
      efficacy rate (clinical outcome) at 5-9 days after drug administration (visit 2)
      were 94.9%. Determination of the microbiological and clinical outcomes for the
      evaluation of recurrence at 4-6 weeks after drug administration (visit 3) were
      75.8 and 85.7%, respectively. Of the 48 patients, 40 (83.3%) returned to the
      clinic at visit 3. The causative bacterial species for cystitis was Escherichia
      coli in 31 (79.5%) of the 39 patients evaluable for efficacy and safety. Adverse
      drug reactions observed during the administration and follow-up periods included
      mild diarrhea and loose stools in 1 patient each, neither requiring any specific
      treatment. Evaluation of cure at visit 2 in patients in whom the causative
      bacterial species for the infection was E. coli revealed a microbiological
      outcome of 93.5%, and clinical outcome was 96.8%. Furthermore, evaluation for
      recurrence at visit 3 revealed a microbiological outcome of 74.1% and clinical
      outcome of 82.1%. When the patients were divided by age into an under 60 years of
      age group and an over 60 years of age group, the microbiological and clinical
      outcomes determined for evaluation of cure at visit 2 were 96.4 and 92.9%,
      respectively, and the corresponding rates determined for the evaluation of
      recurrence at visit 3 were 87.0 and 96.0%, respectively, in the under 60 years of
      age group. In the over 60 years of age group, the corresponding microbiological
      outcome and clinical outcome rates evaluated for cure were 90.9 and 100%,
      respectively, and those evaluated for recurrence were 50.0 and 60.0%,
      respectively. These results indicate the usefulness of fosfomycin calcium
      administered at 1 g three times daily for 2 days for acute uncomplicated
      cystitis.

PMID- 20694572
TI  - The effect of diazepam on myocardial function and coronary vascular tone after
      endotoxemia in the isolated rat heart model.
AB  - OBJECTIVE AND DESIGN: Tumor necrosis factor alpha (TNF-alpha) has been implicated
      in the pathogenesis of cardiovascular disease and sepsis-associated cardiac
      dysfunction. Although initially described solely as a lipopolysaccharide (LPS)
      induced macrophage product, evidence exists that cardiac myocytes themselves
      produce substantial amounts of TNF-alpha in response to ischemia as well as LPS.
      The use of phosphodiesterase inhibitors has been shown to decrease LPS-induced
      TNF-alpha elaboration. The aim of the present study was to determine the effect
      of diazepam (Type IV phosphodiesterase inhibitor) on (1) myocardial function and
      (2) coronary vascular flow after LPS-induced endotoxic shock in an isolated rat
      heart model. MATERIALS AND METHODS: Endotoxemia was induced by intraperitoneal
      LPS administration in adult male Wistar rats. Hearts were isolated after 6 h and
      perfused in a working mode with oxygenated Krebs-Henseleit buffer at 37 degrees
      C. Diazepam was mixed with Krebs-Henseleit buffer and administered (3.0 MUg/ml)
      for 20 min. RESULTS: LPS-treated hearts showed depressed cardiac function and
      reduced coronary flow. Myocardial functional parameters (LVDP, +dP/dt, -dP/dt,
      RPP) and coronary flow (ml/min) were significantly (p < 0.01) improved by
      diazepam administration. CONCLUSIONS: These findings suggest that diazepam can
      salvage myocardial function and undo coronary vascular constriction in the
      endotoxemic rat heart. These findings are clinically relevant to the treatment of
      cardiovascular depression caused by endotoxic shock.

PMID- 20694573
TI  - Repeated treatments with bevacizumab for recurrent radiation necrosis in patients
      with malignant brain tumors: a report of 2 cases.
AB  - Bevacizumab is expected to constitute a new treatment modality for radiation
      necrosis. In the present cases, we observed a recurrence of radiation necrosis
      after temporary improvement by bevacizumab treatment. Re-treatment with
      bevacizumab controlled the necrosis again. A 39-year-old male and a 57-year-old
      female were diagnosed with glioblastoma and lung cancer metastasis, respectively.
      The former patient underwent partial resection of the glioblastoma, followed by
      boron neutron capture therapy (BNCT) and 30 Gy of fractionated X-ray
      radiotherapy. Eleven months after BNCT, he suffered from left hemiparesis and
      convulsions with enlargement of a perifocal edema. The latter patient underwent
      stereotactic radiosurgery twice for the same tumor. Three months after the second
      radiosurgery, she had an uncontrollable convulsion and right hemiplegia with a
      massive perifocal edema. Both lesions were suggested to be radiation necroses by
      positron emission tomography using amino acids as a tracer. Neither patient
      responded to corticosteroids, anticoagulants, or vitamin E. They underwent
      treatment with 5 mg/kg bevacizumab biweekly, for a total of 6 cycles. The size of
      the perifocal edema was clearly reduced in response to the treatments. The
      neurological status of the patients improved concomitant with therapy. However,
      the clinical status of both patients was aggravated several months after the
      bevacizumab was stopped, and the perifocal edemas enlarged again. The patients
      underwent a second treatment with bevacizumab, and the perifocal edemas again
      decreased. Although radiation necrosis may recur several months after bevacizumab
      treatment, repeated bevacizumab treatments also appear to be effective.

PMID- 20694574
TI  - Factors associated with preservation of facial nerve function after surgical
      resection of vestibular schwannoma.
AB  - Avoidance of facial nerve palsy is one of the major goals of vestibular
      schwannoma (VS) microsurgery. In this study, we examined the significance of
      previously implicated prognostic factors (age, tumor size, the extent of
      resection and the surgical approach) on post-operative facial nerve function. We
      selected all VS patients from prospectively collected database (1984-2009) who
      underwent microsurgical resection as their initial treatment for
      histopathologically confirmed VS. The effect of variables such as surgical
      approach, tumor size, patient age and extent of resection on rates facial nerve
      dysfunction after surgery, were analyzed using multivariate logistic regression.
      Patients with preoperative facial nerve dysfunction (House-Brackman [HB] score 3
      or higher) were excluded, and HB grade of 1 or 2 at the last follow-up visit was
      defined as "facial nerve preservation." A total of 624 VS patients were included
      in this study. Multivariate logistic regression analysis found that only pre
      operative tumor size significantly predicted poorer facial nerve outcome for
      patients followed-up for >=6 and >=12 months (OR 1.27, 95% CI 1.09-1.49, p <
      0.01; OR 1.35, 95% CI 1.10-1.67, P < 0.01, respectively). We found no significant
      relationship between facial nerve function and age, extent of resection, surgical
      approach, or tumor size (when extent of resection and surgical approach were
      included in the regression analysis). Because facial nerve palsy is a
      debilitating and psychologically devastating condition for the patient, we
      suggest altering surgical aggressiveness in patients with unfavorable tumor
      anatomy, particularly in cases with large tumors where overaggressive resection
      might subject the patient to unwarranted risk. Residual disease can be followed
      and controlled with radiosurgery if interval growth is noted.

PMID- 20694575
TI  - Residue 544 in domain III of the Bacillus thuringiensis Cry1Ac toxin is involved
      in protein structure stability.
AB  - A unique residue W544 in the beta18-beta19 loop of the Bacillus thuringiensis
      Cry1Ac toxin has been implicated in its toxicity. In this study, the effects of
      mutations at this residue on protein stability during protease treatment, UV
      irradiation, and preservation were examined. Residue 544 of Cry1Ac was involved
      in maintaining structural stability, and substitution of a polar group at this
      position was unfavorable to protein stability. One mutant, W544F, produced larger
      crystals and was more stable. This mutant showed greater resistance to UV
      radiation than the wild type Cry1Ac but retained equal toxicity. This is the
      first report showing that residue 544 in the Cry1Ac domain III plays a
      significant role in toxin structural stability. Our W544F mutant is a significant
      development in terms of field applications of Cry1Ac toxin.

PMID- 20694576
TI  - Growing up in violent communities: do family conflict and gender moderate impacts
      on adolescents' psychosocial development?
AB  - This study examined the moderating effects of family conflict and gender on the
      relationship between community violence and psychosocial development at age 18.
      The study sample consisted of 728 children and families who were part of the
      Infant Health and Development Program study of low-birth-weight, pre-term
      infants. In this sample, adolescent psychosocial outcomes were predicted by
      community violence differently for male and female children and based on their
      experiences of conflict at home. For male children, being in a high conflict
      family as a child exacerbated the negative effects of community violence such
      that internalizing problems (depression and anxiety) and risk-taking behaviors
      increased as community violence increased, while being in a low conflict family
      protected the child against the negative impacts of the community. For female
      adolescents, there were no moderating effects of family conflict on the
      relationship between community violence and externalizing problems. Moderating
      effects for internalizing problems demonstrated that being in low conflict
      families did not serve as protection against community violence for girls as was
      demonstrated for boys. These findings demonstrate the long-term effects of
      community violence on child development, highlighting the importance of gender
      and family context in the development of internalizing and externalizing
      problems.

PMID- 20694577
TI  - The role of friends' disruptive behavior in the development of children's tobacco
      experimentation: results from a preventive intervention study.
AB  - Having friends who engage in disruptive behavior in childhood may be a risk
      factor for childhood tobacco experimentation. This study tested the role of
      friends' disruptive behavior as a mediator of the effects of a classroom based
      intervention on children's tobacco experimentation. 433 Children (52% males) were
      randomly assigned to the Good Behavior Game (GBG) intervention, a universal
      preventive intervention targeting disruptive behavior, and facilitating positive
      prosocial peer interactions. Friends' disruptive behavior was assessed from age 7
      10 years. Participants' experimentation with tobacco was assessed annually from
      age 10-13. Reduced rates in tobacco experimentation and friends' disruptive
      behavior were found among GBG children, as compared to controls. Support for
      friends' disruptive behavior as a mediator in the link between intervention
      status and tobacco experimentation was found. These results remained after
      controlling for friends' and parental smoking status, and child ADHD symptoms.
      The results support the role of friends' disruptive behavior in preadolescents'
      tobacco experimentation.

PMID- 20694578
TI  - Spiritual well-being, cortisol, and suicidality in Croatian war veterans
      suffering from PTSD.
AB  - We present our preliminary results of work that aims to observe the relationship
      between the cortisol level, the level of spiritual well-being, and suicidal
      tendencies in Croatian war veterans suffering from PTSD. The survey was conducted
      on 17 PTSD veterans who completed the Spiritual Well-Being Scale and the Beck
      Hopelessness Scale. The plasma cortisol level was obtained by venepuction at
      8.00, 12.00, 13.00, 16.00, and 22.00 h. Results showed that veterans with higher
      spiritual well-being scores had lower cortisol levels, and evening cortisol
      levels showed significant correlation with suicidal risk. The results of the
      present study could be a stimulus for further investigation into spiritually
      based interventions, exploring their impact both on mental status and physical
      health.

PMID- 20694579
TI  - Blood clearance kinetics, biodistribution, and radiation dosimetry of a kit
      formulated integrin alphavbeta3-selective radiotracer 99mTc-3PRGD 2 in non-human
      primates.
AB  - PURPOSE: (99m)Tc-3PRGD(2) is a (99m)Tc-labeled dimeric cyclic RGD peptide with
      increased receptor binding affinity and improved kinetics for in vivo imaging of
      integrin alpha(v)beta(3) expression in nude mouse model. To accelerate its
      clinical translation, we reported here the evaluation of the kit-formulated
      (99m)Tc-3PRGD(2) in healthy cynomolgus primates for its blood clearance kinetics,
      biodistribution, and radiation dosimetry. PROCEDURES: Healthy cynomolgus primates
      (4.1 +/- 0.7 kg, n = 5) were anesthetized, and the venous blood samples were
      collected via a femoral vein catheter at various time points after injection of
      ~555 MBq of (99m)Tc-3PRGD(2). Serial whole-body scans were performed with a dual
      head single photon emission computed tomography system after administering ~555
      MBq of (99m)Tc-3PRGD(2) in the non-human primates, and the radiation dosimetry
      estimate was calculated. RESULTS: (99m)Tc-3PRGD(2) could be easily obtained from
      freeze-dried kits with high radiochemical purity (>95%) and high specific
      activity (~5 Ci/MUmol). (99m)Tc-3PRGD(2) had a rapid blood clearance with less
      than 1% of the initial radioactivity remaining in the blood circulation at 60 min
      postinjection. No adverse reactions were observed up to 4 weeks after the
      repeated dosing. The whole-body images exhibited high kidney uptake of (99m)Tc
      3PRGD(2) and high radioactivity accumulation in the bladder, demonstrating the
      rapid renal clearance of this tracer. The highest radiation doses of (99m)Tc
      3PRGD(2) were found in the kidneys (13.2 +/- 1.08 MUGy/MBq) and the bladder wall
      (33.1 +/- 1.91 MUGy/MBq). CONCLUSION: (99m)Tc-3PRGD(2) can be readily available
      using the kit formulation. This tracer is safe and well tolerated, and no adverse
      events occurred in non-human primates. Further clinical testing and translation
      of (99m)Tc-3PRGD(2) for noninvasive imaging of integrin alpha(v)beta(3) in humans
      are warranted.

PMID- 20694580
TI  - Bioaccumulation of trace elements in trophic levels of wetland plants and
      waterfowl birds.
AB  - Present study investigates relationships between total and bioaccessibility of
      trace elements (Cd, Co, Cr, Cu, Mn, NI, Pb, V, and Zn) concentrations in sediment
      and their bioaccumulation in species in Shadegan wetland in southwest of Iran.
      Bioavailability factor (BAF) and translocation factor (TF) were calculated in
      plants and trophic transfer factor (TTF) was determined in bird species. For this
      purpose, sampling of sediments, aquatic plants including Phragmites australis,
      Typha australis, Scripus maritimus and two bird species encircling Porphyrio
      porphyrio and globally threatened Marmaronetta angustirostris were carried out
      during winter 2009. Result of chemical analysis show that bioaccessibility
      concentrations of Mn (8.31 mg/kg), V (1.33 mg/kg), and Pb (1.03 mg/kg) are higher
      than other metals. The uptake trend of trace elements in plant decreases as root
      > stem > leaf. Accumulation levels of trace elements in different tissues of P.
      porphyrio and M. angustirostris are almost identical and considerable.
      Accumulation and toxicity of Cd in birds is more than plants. In addition, BAF of
      V, Pb, and Cr indicates high accumulation by plants and great pollution rate in
      the area of study. In S. maritimus TF for Mn, Cu, Pb, and V are high whereas in
      T. australis, Cu and Pb posses the highest TF. Also Cr, Co, Mn, Ni, and Zn have
      higher TF from stem to leaf than root to stem in P. australis. Finally, TTFs were
      compared in various bird species.

PMID- 20694581
TI  - The proliferation and differentiation of stem cell journals.
AB  - As scientists position themselves in translating the therapeutic potential of
      stem cells from laboratory to clinical applications, publishing companies have
      taken this rapidly evolving field as a unique opportunity to launch new journals
      for dissemination of stem cell research. Over the last decade, the significant
      increase in the number of stem cell-based journals has created a conundrum. At
      stake is the pressure for these new journals to build their reputation by
      maintaining publication standards, while at the same time attracting a cadre of
      stem cell researchers to consider their journals as the publication of choice. We
      discuss here a prophetic path of survival for these journals which likely will
      closely mimic the core scientific and translational value of stem cells, namely
      their capacity to proliferate and differentiate into something meaningful!

PMID- 20694582
TI  - Enhanced functions of human embryonic stem cell-derived hepatocyte-like cells on
      three-dimensional nanofibrillar surfaces.
AB  - Human embryonic stem cell (hESC)-derived hepatocytes provide a promising
      unlimited resource for the treatment of liver disease. However, current protocols
      for the generation of mature and functional hepatocytes are inefficient.
      Therefore, in order to better differentiate and maintain the function of
      differentiating hESCs, we have hypothesized that hESCs undergo better
      differentiation into hepatocyte-like cells (HLCs) when induced on three
      dimensional nanofibrillar surfaces. We have demonstrated that, during stepwise
      differentiation of induction, the markers of hepatic lineage expressed and
      finally lead to the generation of functional mature cells. In the presence of an
      ultraweb nanofiber, HLCs produced lower AFP, greater urea, glycogen storage,
      metabolic PROD activity, uptake of LDL and organic anion ICG, all of which are
      indicative of the differentiation of HLCs. These results show that
      topographically treated hESCs at the nano level have a distinct hepatic
      functionality profile which has implications for cell therapies.

PMID- 20694583
TI  - Attention-deficit/Hyperactivity Disorder in the context of Autism spectrum
      disorders.
AB  - Autism spectrum disorders (ASD) are frequently marked by symptoms consistent with
      attention-deficit/hyperactivity disorder (ADHD), namely inattention,
      hyperactivity, and impulsivity. Recent work has established that about half of
      the ASD population also meets diagnostic criteria for ADHD, although the comorbid
      diagnoses are precluded by the DSM-IV-TR. Individuals with co-occurring ASD and
      ADHD symptoms are more severely impaired, with significant deficits seen in
      social processing, adaptive functioning, and executive control. Children with ASD
      and ADHD symptoms are also prone to motor problems, which lead to especially poor
      outcomes. Recent work has also demonstrated high rates of ASD symptoms in a
      subset of children with ADHD. Medication studies have demonstrated the efficacy
      of methylphenidate, atomoxetine, and guanfacine, among others, in treating ADHD
      symptoms co-occurring with ASD. However, these effects were not as great as those
      seen when treating primary ADHD, and they are less well-tolerated in the ASD
      population.

PMID- 20694584
TI  - Economic consequences of severe bleeding in patients with acute coronary syndrome
      in the USA.
AB  - INTRODUCTION: Previous studies have demonstrated increased costs associated with
      bleeding in clinical trials, but none have yet examined the association of
      bleeding with costs/charges in a real-world setting. This study examines the
      association between health care charges and severe bleeding events among patients
      with acute coronary syndrome (ACS) in a real-world US setting. METHODS: This
      retrospective study of ACS patients enrolled in a regional, 570,000-member
      commercial health plan evaluated resource utilization for patients with and
      without severe bleeding using medical encounter data in health care
      administrative records. Inclusion criteria were continuous health plan enrollment
      in the 6 months before initial ACS-related hospitalization, age of at least 18
      years, and an inpatient ACS claim between January 1995 and May 2007. Severe
      bleeding events were defined as having an in-hospital record for: (a) bleeding
      plus blood transfusion, (b) intracranial hemorrhage, or (c) blood transfusion
      followed by death. Hospitalizations in which the patient had a nonsevere bleeding
      event, defined as having an International Classification of Diseases, Ninth
      Revision, Clinical Modification (ICD-9-CM) code for bleeding without transfusion
      or death, were removed from analysis. Resource utilization was assessed using
      hospital charges. Multiple linear regression analyses controlling for key
      covariates were used to assess the association of severe bleeding during initial
      hospitalization with an ACS diagnosis/procedure with charges and length of stay
      (LOS). RESULTS: There were 11,266 ACS patients identified: 928 patients (8.2%)
      had severe bleeding during initial hospitalization. Severe bleeding events were
      associated with significantly higher hospital charges and increased LOS than
      hospitalizations without severe bleeding events. After adjusting for patient
      characteristics, in-hospital ACS-related procedures, and LOS, patients with
      severe bleeding incurred initial hospitalization charges that were $48,114 higher
      than those of patients without bleeding (P<0.001). CONCLUSION: In a real-world
      setting, hospitalizations with both severe bleeding and an ACS diagnosis or
      procedure are associated with significantly higher hospitalization charges and
      resource use compared with ACS-related hospitalizations without bleeding events.
      However, due to the limitations of retrospective analyses, no causal relationship
      can be determined as patient comorbidities represent a possible source of
      confounding.

PMID- 20694585
TI  - Incremental prognostic value of left ventricular function analysis over non
      invasive coronary angiography with multidetector computed tomography.
AB  - BACKGROUND: The purpose of this study was to determine the prognostic value of
      computed tomography coronary angiography (CTA)-derived left ventricular (LV)
      function analysis and to assess its incremental prognostic value over the
      detection of significant stenosis using CTA. METHODS: In 728 patients (400 males,
      mean age 55 +/- 12 years) with known or suspected CAD, the presence of
      significant stenosis (>= 50% stenosis) and LV function were assessed using CTA.
      LV end-systolic volume (LVESV), LV end-diastolic volume (LVEDV), and LV ejection
      fraction (LVEF) were calculated. LV function was assessed as a continuous
      variable and using cutoff values (LVEDV > 215 mL, LVESV > 90 mL, LVEF < 49%). The
      following events were combined in a composite end-point: all-cause mortality, non
      fatal myocardial infarction, and unstable angina pectoris requiring
      hospitalization. RESULTS: On CTA, a significant stenosis was observed in 221
      patients (30%). During follow-up [median 765 days, 25-75th percentile: 493-978]
      an event occurred in 45 patients (6.2%). After multivariate correction for
      clinical risk factors and CTA, LVEF < 49% and LVESV > 90 mL were independent
      predictors of events with an incremental prognostic value over clinical risk
      factors and CTA. CONCLUSIONS: The present results suggest that LV function
      analysis provides independent and incremental prognostic information beyond
      anatomic assessment of CAD using CTA.

PMID- 20694658
TI  - A review of post-translational modifications and subcellular localization of Ets
      transcription factors: possible connection with cancer and involvement in the
      hypoxic response.
AB  - Post-translational modifications and subcellular localizations modulate
      transcription factors, generating a code that is deciphered into an activity. We
      describe our current understanding of these processes for Ets factors, which have
      recently been recognized for their importance in various biological processes. We
      present the global picture for the family, and then focus on particular aspects
      related to cancer and hypoxia. The analysis of Post-translational modification
      and cellular localization is only beginning to enter the age of "omic," high
      content, systems biology. Our snap-shots of particularly active fields point to
      the directions in which new techniques will be needed, in our search for a more
      complete description of regulatory pathways.

PMID- 20694586
TI  - Heat-shock protein expression in leukemia.
AB  - Heat-shock proteins (Hsps) are thought to play a role in the development of
      cancer and to modulate tumor response to cytotoxic therapy. In this study, Hsp27,
      Hsp60, Hsp90alpha, and HspBP1 gene expression was investigated in human leukemia
      cell lines as well as in leukemia cells derived from patients with the onset of
      the disease. Hsp70 membrane expression and expression of Hsp27, Hsp60, Hsp70,
      Hsp90alpha, and HspBP1 genes were also tested in samples from leukemia patients.
      Relative Hsps gene expression was examined in human leukemia cell lines and also
      in patients, using real-time quantitative reverse-transcriptase polymerase chain
      reaction (RT-PCR). Hsp70 cell surface expression was studied in patients with
      leukemia onset using flow cytometry. All tested cell lines showed significantly
      increased expression of Hsp60, Hsp90alpha, and HspBP1 genes compared with a
      cohort of healthy controls; additionally there was increased Hsp27 expression
      except for Jurkat and CCRF cells. Significantly higher gene expression of Hsp27,
      Hsp60, Hsp90alpha, and HspBP1 was observed in the peripheral blood of patients
      compared with bone marrow and healthy control samples, while Hsp70 expression was
      without any significant difference among cohorts. Hsp70 cell surface expression
      was found on defrosted and cultured leukemia cells but not on unprocessed
      biological samples from patients. Leukemia cells showed a heterogeneous pattern
      of Hsp gene expression among leukemia cell lines as well as in peripheral blood
      and bone marrow of patients.

PMID- 20694659
TI  - Regulation of transcription factor function by targeted protein degradation: an
      overview focusing on p53, c-Myc, and c-Jun.
AB  - Regulation of protein degradation is an important mechanism by which
      concentrations of proteins is controlled in cells. In addition to proteins
      involved in cell cycle regulation or mitosis, protein levels of many
      transcription factors are regulated by targeted proteosomal degradation.
      Regulation of protein degradation and stability is usually linked to post
      translational modification of the target protein by phosphorylation. The
      resulting phosphoaminoacid in the context of the adjacent protein sequence is
      then recognized by E3 ubiquitin ligase enzymes that covalently attach small
      ubiquitin protein to the target protein and thereby direct them to be degraded by
      the proteosomes. Here, we present an overview of mechanisms regulating stability
      of p53, c-Myc, and c-Jun transcription factors. Especially, the purpose is to
      highlight the role of protein phosphorylation in the regulation of stability of
      these transcription factors. We also present examples where phosphorylation can
      either enhance or inhibit protein degradation. Lastly, we discuss the common
      theme among p53, c-Myc, and c-Jun proteins that the N-terminal phosphorylation
      both increases the transactivation capacity of the protein and protects the
      protein from proteolytic degradation.

PMID- 20694660
TI  - Review of molecular mechanisms involved in the activation of the Nrf2-ARE
      signaling pathway by chemopreventive agents.
AB  - Human exposures to environmental toxicants have been associated with etiology of
      many diseases including inflammation, cancer, and cardiovascular and
      neurodegenerative disorders. To counteract the detrimental effect of
      environmental insults, mammalian cells have evolved a hierarchy of sophisticated
      sensing and signaling mechanisms to turn on or off endogenous antioxidant
      responses accordingly. One of the major cellular antioxidant responses is the
      induction of antioxidative and carcinogen-detoxification enzymes through the
      cytoplasmic oxidative stress system (Nrf2-Keap1) activated by a variety of
      natural and synthetic chemopreventive agents. Under normal conditions, Keap1
      anchors the Nrf2 transcription factor within the cytoplasm targeting it for
      ubiquitination and proteasomal degradation to maintain low levels of Nrf2 that
      mediate the constitutive expression of Nrf2 downstream genes. When cells are
      exposed to chemopreventive agents and oxidative stress, a signal involving
      phosphorylation and/or redox modification of critical cysteine residues in Keap1
      inhibits the enzymatic activity of the Keap1-Cul3-Rbx1 E3 ubiquitin ligase
      complex, resulting in decreased Nrf2 ubiquitination and degradation. As a
      consequence, free Nrf2 translocates into the nucleus and in combination with
      other transcription factors (e.g., sMaf, ATF4, JunD, PMF-1) transactivates the
      antioxidant response elements (AREs)/electrophile response elements (EpREs) of
      many cytoprotective genes, as well as Nrf2 itself. Upon recovery of cellular
      redox homeostasis, Keap1 travels into the nucleus to dissociate Nrf2 from the
      ARE. Subsequently, the Nrf2-Keap1 complex is exported out of the nucleus by the
      nuclear export sequence (NES) in Keap1. Once in the cytoplasm, the Nrf2-Keap1
      complex associates with the Cul3-Rbx1 core ubiquitin machinery, resulting in
      degradation of Nrf2 and termination of the Nrf2/ARE signaling pathway. The
      discovery of multiple nuclear localization signals (NLSs) and nuclear export
      signals (NESs) in Nrf2 also suggests that the nucleocytoplasm translocation of
      transcription factors is the consequence of a dynamic equilibrium of multivalent
      NLSs and NESs. On the other hand, Keap1 may provide an additional regulation of
      the quantity of Nrf2 both in basal and inducible conditions. This chapter
      summarizes the current body of knowledge regarding the molecular mechanisms
      through which ARE inducers (chemopreventive agents) regulate the coordinated
      transcriptional induction of genes encoding phase II and antioxidant enzymes as
      well as other defensive proteins, via the nuclear factor-erythroid 2 (NF-E2-p45)
      related factor 2(Nrf2)/(ARE) signaling pathway.

PMID- 20694661
TI  - Subnuclear localization and intranuclear trafficking of transcription factors.
AB  - Nuclear microenvironments are architecturally organized subnuclear sites where
      the regulatory machinery for gene expression, replication, and repair resides.
      This compartmentalization is necessary to attain required stoichiometry for
      organization and assembly of regulatory complexes for combinatorial control.
      Combined and methodical application of molecular, cellular, biochemical, and in
      vivo genetic approaches is required to fully understand complexities of
      biological control. Here we provide methodologies to characterize nuclear
      organization of regulatory machinery by in situ immunofluorescence microscopy.

PMID- 20694662
TI  - Analysis of ligand-dependent nuclear accumulation of Smads in TGF-beta signaling.
AB  - The growth inhibition of dividing cells and most of the transcriptional responses
      upon TGF-beta treatment depend on the Smad2, Smad3, and Smad4 transcription
      factors. These proteins shuttle continuously between the cytoplasm and the
      nucleus, transmitting the ligand status of the TGF-beta receptors to the nuclear
      transcription machinery. In the absence of TGF-beta ligand, Smads 2/3/4 reside
      predominantly in the cytoplasm. Following ligand binding to the TGF-beta
      receptors, the dynamic equilibrium of shuttling Smads 2/3/4 shifts toward a
      predominantly nuclear state, where a high concentration of these transcription
      factors drives transcriptional activation and repression of genes required for
      proper cellular response. Here, we describe live cell imaging and
      immunofluorescence microscopy methods for tracking Smads subcellular localization
      in response to TGF-beta and leptomycin B treatment. In addition, a method of
      fractionating nuclear and cytoplasmic proteins used to confirm the imaging
      results was presented. Our results support the notion that the R-Smad shuttling
      mechanism is distinct from Co-Smad.

PMID- 20694663
TI  - Raf/MEK/MAPK signaling stimulates the nuclear translocation and transactivating
      activity of FOXM1.
AB  - The proliferation-associated transcription factor FOXM1 is essential for cell
      cycle progression into mitosis. Using synchronized human fibroblasts we detected,
      by immunostaining, that FOXM1 is localized predominantly in the cytoplasm in
      cells at late-G1 and S phases. Nuclear translocation occurs just before
      progression into the G2/M phase of the cell cycle and requires activity of the
      Raf/MEK/MAPK signaling pathway. Using pharmacological modulators, we demonstrated
      that activity of the Raf/MEK/MAPK pathway is both necessary and sufficient for
      the nuclear translocation of FOXM1. Consistent with FoxM1c being the major
      isoform expressed in proliferating fibroblasts, constitutively active MEK1
      enhances the transactivating effect of FOXM1c, but not FOXM1b, on the cyclin B1
      promoter in transient reporter assays. Here, we describe in detail the methods
      involved in generating these findings, which support the notion that FOXM1 is an
      effector of Raf/MEK/MAPK signaling in G2/M regulation.

PMID- 20694664
TI  - Coupling of dephosphorylation and nuclear export of Smads in TGF-beta signaling.
AB  - In eukaryotes, regulation of signaling mediators/effectors in the nucleus is one
      of the principal mechanisms that govern duration and strength of signaling. Smads
      are a family of structurally related intracellular proteins that serve as
      signaling effectors for transforming growth factor beta (TGF-beta) and TGF-beta
      related proteins. Accumulating evidence demonstrates that Smads possess intrinsic
      nucleocytoplasmic shuttling capacity, which enables them to transmit TGF-beta
      signals from cell membrane to nucleus. We recently identified two important steps
      in the termination of nuclear Smad signaling. The first step is initiated by a
      serine/threonine phosphatase PPM1A that dephosphorylates Smad2/3 in the nucleus,
      thereby shutting down signaling capacity of phosphorylated Smad2/3. The second
      step involves nuclear export of dephosphorylated Smad2/3 with the aid of nuclear
      protein RanBP3 to terminate Smad signaling. This chapter introduces methods for
      examining nuclear export of Smad2/3 in TGF-beta signaling.

PMID- 20694665
TI  - Assessing sequence-specific DNA binding and transcriptional activity of STAT1
      transcription factor.
AB  - Continuous nucleocytoplasmic shuttling of signal transducer and activator of
      transcription (STAT) proteins is a key to understand their function as cytokine
      responsive transcription factors. STATs enter the nucleus both by carrier
      dependent and carrier-independent transport pathways, and it was previously shown
      that STAT1 exits the nucleus only after its prior enzymatic dephosphorylation by
      nuclear phosphatases. The identification of different transport pathways for
      unphosphorylated and tyrosine-phosphorylated STAT dimers was made possible by a
      combination of a diverse set of experimental approaches in the field of molecular
      biology. In the following, we will summarize some of the techniques that have
      been successfully used to decipher molecular mechanisms engaged in STAT1
      dynamics.

PMID- 20694666
TI  - Analysis of nuclear export using photoactivatable GFP fusion proteins and
      interspecies heterokaryons.
AB  - In this chapter, we review protocols for the analysis of nucleocytoplasmic
      shuttling of transcription factors and nuclear proteins, using two different
      approaches. The first involves the use of photoactivatable forms of the protein
      of interest by fusion to photoactivatable green fluorescent protein to follow its
      movement out of the nucleus by live-cell confocal microscopy. This methodology
      allows for the kinetic characterization of protein movements as well as
      measurement of steady-state levels. In a second procedure to assess the ability
      of a nuclear protein to move into and out of the nucleus, we describe the use of
      interspecies heterokaryon assays, which provide a measurement of steady-state
      distribution. These technologies are directly applicable to the analysis of
      nucleocytoplasmic movements not only of transcription factors, but also other
      nuclear proteins.

PMID- 20694667
TI  - Determination of nuclear localization signal sequences for Kruppel-like factor 8.
AB  - Transcription factor proteins function in the nucleus to regulate gene
      expression. Many transcription factors are critical regulators of tumor
      progression. Conversely, many oncogenic and tumor suppressor proteins are
      transcription factors or other types of nuclear proteins. Because of their
      critical physiological and pathological roles, these tumor regulators are tightly
      regulated not only in the protein expression but also in their subcellular
      localization. This chapter is focused on experimental strategies and method
      details for the identification and characterization of nuclear localization
      signal sequences for nuclear proteins using the Kruppel-like transcription factor
      8 as an example.

PMID- 20694668
TI  - Methods to measure nuclear export of beta-catenin using fixed and live cell
      assays.
AB  - beta-Catenin is a multifunctional protein which is overexpressed in several types
      of cancers. The subcellular location of beta-catenin at the membrane junctions or
      in the nucleus determines its function in cell adhesion and transcription
      activation, respectively. The aberrant localization of beta-catenin in the
      nucleus activates transcription of a number of genes involved in cancer
      progression. Our laboratory studies intracellular trafficking of beta-catenin
      with particular emphasis on its movement and regulation in and out of the
      nucleus. In this chapter, we outline a number of assays to measure the nuclear
      export of beta-catenin in fixed and live cells.

PMID- 20694669
TI  - Imaging of transcription factor trafficking in living cells: lessons from
      corticosteroid receptor dynamics.
AB  - Adrenal corticosteroids (cortisol in humans/corticosterone in rodents) readily
      enter the brain and exert markedly diverse effects, such as the stress response
      of target neural cells. These effects are regulated via two receptor systems, the
      mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR), both are
      ligand-inducible transcription factors. GR and MR predominantly reside in the
      cytoplasm in the absence of corticosterone (CORT), but are quickly translocated
      into the nucleus upon binding CORT. Then these receptors form dimers to bind
      hormone responsive elements and regulate the expression of target genes. Given
      the different actions of MR and GR in the central nervous system, it is important
      to elucidate how the trafficking of these receptors between the cytoplasm and
      nucleus and their interaction are regulated by ligands or other molecules to
      exert transcriptional activity. However, these processes have still not been
      completely clarified. To address these issues, we have tried to observe more
      dynamic subcellular trafficking processes in living cells by employing a green
      fluorescent protein (GFP). In this chapter, we describe our recent studies of
      corticosteroid receptor dynamics in living cells focusing on three points: (1)
      time-lapse imaging of GFP-labeled corticosteroid receptors; (2) intranuclear
      dynamics of GFP-labeled corticosteroid receptors using the fluorescence recovery
      after photobleaching (FRAP) technique; and (3) the possibility of heterodimers
      formation using the fluorescence resonance energy transfer (FRET) technique.
      These studies demonstrate that GR and MR were quickly translocated from the
      cytoplasm to nucleus after CORT treatment. The time course of the nuclear
      translocation of GR and MR differed depending on the concentration of CORT. The
      FRAP study showed that liganded GR and MR in the nucleus were highly mobile, and
      not trapped by specific organelles. We detected GR-MR heterodimers, which were
      affected by changes in CORT concentrations in response to various hormonal milieu
      such as circadian rhythm and stress. Our findings may provide new insights into
      the dynamic status of corticosteroid receptors in living cells and the molecular
      basis of the regulation of stress by these receptors.

PMID- 20694670
TI  - Hypoxia-inducible factors: post-translational crosstalk of signaling pathways.
AB  - Hypoxia-inducible factor-1 (HIF-1) has a central role in the mammalian program by
      which cells respond to hypoxia in both physiological and pathological situations.
      HIF-1 transcriptional activity, protein stabilization, protein-protein
      interaction, and cellular localization are mainly modulated by Post-translational
      modifications such as hydroxylation, acetylation, phosphorylation, S
      nitrosylation, and SUMOylation. Here, we summarize current knowledge about Post
      translational HIF-1 regulation and give additional information about useful
      methods to determine some of these various modifications.

PMID- 20694671
TI  - The basic-helix-loop-helix-leucine zipper gene Mitf: analysis of alternative
      promoter choice and splicing.
AB  - The activity of transcription factors is often regulated by Post-translational
      modifications. A precondition for such modifications is the presence, in the
      corresponding mRNAs, of the exons that either directly encode the modifiable
      residues in question, or encode protein domains that influence their modification
      indirectly. The inclusion or exclusion of coding exons is regulated predominantly
      by alternative splicing but can also depend on promoter choice and
      polyadenylation site selection. Information about exon inclusion and exclusion,
      both qualitatively and quantitatively, is particularly important for experiments
      designed to mutate endogenous codons because such mutations can alter splicing
      patterns. Therefore, we here describe methods employed to quantitate exon
      inclusion and exclusion, using as example a mouse transcription factor gene,
      Mitf.

PMID- 20694672
TI  - Phosphorylation control of nuclear receptors.
AB  - Most transcription factors including nuclear receptors (NRs) act as sensors of
      the extracellular and intracellular compartments. As such, NRs serve as
      integrating platforms for a variety of stimuli and are targets for Post
      translational modifications such as phosphorylations. During the last decade,
      knowledge of NRs phosphorylation advanced considerably because of the emergence
      of new technologies. Indeed, the development of a wide range of phosphorylation
      site databases, high accuracy mass spectrometry, and phospho-specific antibodies
      allowed the identification of multiple novel phosphorylation sites in NRs. New
      and improved methods also emerge to connect these data with the downstream
      consequences of phosphorylation on NRs structure (computational prediction, NMR),
      intracellular localization (FRAP), interaction with coregulators (proteomics,
      FRET, FLIM), and affinity for DNA (ChIP, ChIP-seq, FRAP). In the future, such
      integrated strategies should provide data with a treasure-trove of information
      about the integration of numerous signaling events by NRs.

PMID- 20694673
TI  - Regulation of Krupple-like factor 5 by targeted protein degradation.
AB  - Transcription factors are usually unstable proteins. The degradation of the
      majority of transcription factors is through the ubiquitin proteasome pathway and
      is tightly regulated by E3 ubiquitin ligases. KLF5 is an important transcription
      factor regulating cell proliferation, cell cycle, survival, migration,
      differentiation, angiogenesis, and stem cell self-renewal. We have shown that the
      WWP1 E3 ligase targets KLF5 for ubiquitin-mediated degradation. Several methods
      to determine whether a protein is ubiquitinated have been described [Kaiser,
      Tagwerker (Methods Enzymol 399:243-248, 2005); Bloom, Pagano (Methods Enzymol
      399:249-266, 2005)]. This chapter focuses on experimental approaches testing KLF5
      transcription factor ubiquitination and degradation by its E3s.

PMID- 20694674
TI  - Post-translational control of ETS transcription factors: detection of modified
      factors at target gene promoters.
AB  - ETS transcription factors are implicated in gene regulation during cell
      proliferation and in the development of the haematopoietic cell lineage.
      Characteristically, ETS proteins act in concert with other transcription factors
      and are regulated by post-translational modifications, most frequently
      phosphorylation. These events have been shown to modulate the DNA binding
      affinity and interactions of ETS transcription factors with co-activators, events
      that can ultimately determine the formation of productive transcription complexes
      on target gene promoters. However, direct implication of a transcription factor
      or one of its post-translational modifications in the regulation of a given gene
      requires detection of the modified factor at the target gene promoter. Chromatin
      immunoprecipitation assays were originally adopted to probe modifications to
      histone proteins associated with transcriptionally active genes in yeast. They
      have since been used to confirm the presence of numerous proteins at diverse gene
      promoters including, for example, recruitment of the mitogen-activated protein
      (MAP) kinases ERK1 and ERK2 to the promoters of mitogen-responsive genes. Here
      chromatin immunoprecipitation is used to demonstrate the inducible appearance of
      phosphorylated Elk-1 at the human c-fos promoter.

PMID- 20694675
TI  - Integration of protein kinases into transcription complexes: identifying
      components of immobilised in vitro pre-initiation complexes.
AB  - Regulation of gene expression is essential for coordinated cell growth and
      development. The de-regulation of certain genes is also recognised to contribute
      to both heritable and acquired disease. Transcription factors influence the
      assembly and activity of transcription complexes, which they achieve in part by
      recruiting co-activators to gene promoters to participate in the dynamic cycle of
      polymerase binding, initiation and escape from the promoter. Co-activator
      recruitment and accompanying post-translational modifications to components of
      promoter complexes appear to differ between genes and as a consequence of varying
      signal input. Thus a full understanding of transcriptional initiation and control
      will ultimately require the elucidation of these processes. The method described
      here was designed to detect the presence of proteins and post-translational
      modifications in complexes formed in vitro on gene-specific promoters. It has
      been used, among other things, to detect the recruitment of the Mitogen-Activated
      Protein (MAP) kinases ERK1 and ERK2 to the promoters of mitogen-responsive genes.

PMID- 20694676
TI  - Post-translational modification of p53 by ubiquitin.
AB  - Post-translational modification of p53 by ubiquitin resides in the center of a
      fine-tuned regulatory network that activates the tumor suppressor in response to
      genotoxic stress. Inhibition of p53 ubiquitination by DNA damage not only
      prevents p53 from degradation but also promotes its nuclear accumulation leading
      to transactivation of a number of downstream genes that are essential for the
      control of cell cycle progression, cell survival, and cellular senescence.
      Therefore, there are growing interests in studying p53 ubiquitination under
      physiological/pathological conditions. We describe herein a cell-based method and
      an in vitro reconstituted assay that are convenient, reproducible, and adaptable
      for various experimental conditions for detection of p53 ubiquitination. Wide
      application of these methods in studying mechanisms underlying regulation of p53
      ubiquitination shall assist us in better understanding of the function of the
      tumor suppressor.

PMID- 20694677
TI  - Phosphorylation-dependent regulation of SATB1, the higher-order chromatin
      organizer and global gene regulator.
AB  - The chromatin organizer SATB1 regulates distant genes by selectively tethering
      matrix attachment regions (MARs) to the nuclear matrix. Post-translational
      modifications (PTMs) are important regulators of functional activities of
      proteins. Recently, a phosphorylation-dependent molecular switch that provided
      insights into the molecular mechanism of transcriptional repression and
      activation by SATB1 was discovered. SATB1 is specifically phosphorylated by
      protein kinase C (PKC) at serine 185 in vivo, and this modification leads to
      repression of transcription by SATB1 via increased association with the histone
      deacetylase 1 (HDAC1) corepressor. In this chapter, we describe methods for
      overexpression and purification of full length SATB1 protein and for its in vitro
      phosphorylation. We also describe method for in vivo phosphorylation of SATB1
      upon immunoprecipitation using anti-SATB1. Finally, we describe a functional
      assay to monitor the effect of phosphorylation on transcription activity of SATB1
      in vivo using MAR-linked reporter assay, in the presence and absence of PKC
      inhibitors.

PMID- 20694678
TI  - In vivo and in vitro tools to identify and study transcriptional regulation of
      USF-1 target genes.
AB  - In response to environmental stress, cells trigger a number of molecular
      mechanisms to control their survival and growth. These include changes in gene
      expression with corresponding Post-translational modifications to critical
      transcriptional-control proteins. Transcription is a highly-regulated process
      that is impacted by a large number of ubiquitous and specific factors. In order
      to determine how gene expression is regulated in response to environmental cues,
      it is necessary to correlate modifications to specific transcription proteins
      with an accurate assessment of the transcriptional response. This chapter details
      quantitative Real Time PCR (qPCR) and Luciferase assay protocols to illustrate,
      both in vivo and in vitro, the role of the USF-1 transcription factor in the UV
      dependant regulation of pigmentation genes (POMC and MC1R). The procedures have
      been optimized for the USF-1 transcription factor and the regulation of specific
      target genes in response to physiological UV doses.

PMID- 20694679
TI  - Measuring the absolute abundance of the Smad transcription factors using
      quantitative immunoblotting.
AB  - In the age of systems biology, biologists seek to quantify the absolute number of
      molecules in experimentally treated samples. Immunoblotting remains a technique
      of choice for assessing the relative differences between the protein levels in
      different samples. Here we discuss how to exploit immunoblotting for estimating
      the number of Smad transcription factor molecules per cell. We focus on
      describing the calculations needed to analyze the data. Our methods are generally
      applicable to the quantification of other cellular proteins.

PMID- 20694680
TI  - Flow cytometry analysis of transcription factors in T lymphocytes.
AB  - Detection of transcription factors in immune cell populations, particularly in
      subpopulations that are represented at low frequencies in lymphoid and
      nonlymphoid organs, presents a particular challenge when using traditional
      methods such as western blot analysis. Therefore, development of flow cytometry
      based methods which allow identification of transcription factors in specific
      immune cell populations is of main interest. Here we developed and optimized a
      methodology for rapid and convenient detection of the transcription factor BCL11B
      in T lymphocyte subpopulations using flow cytometry. The optimal protocol employs
      saponin and Tween 20 both during the fixation and permeabilization steps, and we
      demonstrate that it is efficient for three anti-BCL11B antibodies covering
      distinctive BCL11B epitopes. In addition, we prove that the method preserves the
      staining of surface markers.

PMID- 20694681
TI  - Identification of specific protein/E-box-containing DNA complexes: lessons from
      the ubiquitously expressed USF transcription factors of the b-HLH-LZ super
      family.
AB  - In order to determine how gene expression is regulated in response to
      environmental cues, it is necessary to identify the specific interaction between
      transcription factors and their cognate cis-regulatory DNA elements. Here we have
      out-lined electrophoretic mobility shift assay (EMSA) and chromatin
      immunoprecipitation (ChIP) protocols to define in vitro and in vivo USFs specific
      interacting sequences. The proposed procedures have been optimized for the USFs
      transcription factor family, allowing the identification of USF-specific targets.

PMID- 20694682
TI  - An historical overview of drug discovery.
AB  - Drug Discovery in modern times straddles three main periods. The first notable
      period can be traced to the nineteenth century where the basis of drug discovery
      relied on the serendipity of the medicinal chemists. The second period commenced
      around the early twentieth century when new drug structures were found, which
      contributed for a new era of antibiotics discovery. Based on these known
      structures, and with the development of powerful new techniques such as molecular
      modelling, combinatorial chemistry, and automated high-throughput screening,
      rapid advances occurred in drug discovery towards the end of the century. The
      period also was revolutionized by the emergence of recombinant DNA technology,
      where it became possible to develop potential drugs target candidates. With all
      the expansion of new technologies and the onset of the "Omics" revolution in the
      twenty-first century, the third period has kick-started with an increase in
      biopharmaceutical drugs approved by FDA/EMEA for therapeutic use.

PMID- 20694683
TI  - Ligand macromolecule interactions: theoretical principles of molecular
      recognition.
AB  - Molecular recognition is mediated by three main factors: surface complementarity,
      thermodynamics, and associated physicochemical properties. These principles are
      responsible for ligand-target binding and therefore serve as the foundation for
      the design of new biologically relevant chemical entities. As these principles
      are involved in nearly all biological processes, a firm understanding of the
      details involved in binding is necessary for drug design. The consideration of
      these factors individually has proven useful; however, the combined effect of
      these governing principles is most important. And despite extensive studies,
      there are still many gaps in our understanding of this recognition process. The
      aim of this chapter is to introduce the basic concepts of ligand binding to set
      the stage for the following chapters, while briefly discussing fundamental
      techniques of drug design, including the indispensable tools of molecular
      modeling.

PMID- 20694684
TI  - X-ray crystallography in drug discovery.
AB  - Macromolecular X-ray crystallography is an important and powerful technique in
      drug discovery, used by pharmaceutical companies in the discovery process of new
      medicines. The detailed analysis of crystal structures of protein-ligand
      complexes allows the study of the specific interactions of a particular drug with
      its protein target at the atomic level. It is used to design and improve drugs.
      The starting point of these studies is the preparation of suitable crystals of
      complexes with potential ligands, which can be achieved by using different
      strategies described in this chapter. In addition, an introduction to X-ray
      crystallography is given, highlighting the fundamental steps necessary to
      determine the three-dimensional structure of protein-ligand complexes, as well as
      some of the tools and criteria to validate crystal structures available in
      databases.

PMID- 20694685
TI  - Virtual screening of compound libraries.
AB  - During the last decade, Virtual Screening (VS) has definitively established
      itself as an important part of the drug discovery and development process. VS
      involves the selection of likely drug candidates from large libraries of chemical
      structures by using computational methodologies, but the generic definition of VS
      encompasses many different methodologies. This chapter provides an introduction
      to the field by reviewing a variety of important aspects, including the different
      types of virtual screening methods, and the several steps required for a
      successful virtual screening campaign within a state-of-the-art approach, from
      target selection to postfilter application. This analysis is further complemented
      with a small collection important VS success stories.

PMID- 20694686
TI  - Combinatorial chemistry and the synthesis of compound libraries.
AB  - Solid Phase Organic Synthesis (SPOS) has become a powerful tool for the
      preparation of compound libraries used for screening efforts in Chemical Biology.
      While different types of screening libraries have become commercially available
      through several vendors, the elaboration of a hit compound in a screening
      campaign to a useful chemical probe still requires the preparation of a focused
      library. In this report, protocols are given which allow the synthesis of a
      focused compound library on solid phase by the diversification of a central
      scaffold using reliable functionalization reactions. Diversity elements can be
      introduced by attaching building blocks via amidation, esterification, reductive
      amination, and Suzuki cross-coupling.

PMID- 20694687
TI  - Ligand-based nuclear magnetic resonance screening techniques.
AB  - A critical step in the drug discovery process is the identification of high
      affinity ligands for macromolecular targets, and, over the last 10 years, NMR
      spectroscopy has become a powerful tool in the pharmaceutical industry.
      Instrumental improvements in recent years have contributed significantly to this
      development. Digital recording, cryogenic probes, autosamplers, and higher
      magnetic fields shorten the time for data acquisition and improve the spectral
      quality. In addition, new experiments and pulse sequences make a vast amount of
      information available for the drug discovery process. All these techniques take
      advantage of the fact that upon complex formation between a target molecule and a
      ligand, significant perturbations can be observed in NMR-sensitive parameters of
      either the target or the ligand. These perturbations can be used qualitatively to
      detect ligand binding or quantitatively to assess the strength of the binding
      interaction. In addition, some of the techniques allow the identification of the
      ligand-binding site or which part of the ligand is responsible for interacting
      with the target.In this chapter, we will use examples from our own research to
      illustrate how NMR experiments to characterize ligand binding may be used to both
      screen for novel compounds during the process of lead generation, and provide
      structural information useful for lead optimization during the latter stages of a
      discovery program.

PMID- 20694688
TI  - Isothermal titration calorimetry and differential scanning calorimetry.
AB  - Isothermal titration [Holdgate (BioTechniques 31:164-184, 2001); Ward and
      Holdgate (Prog. Med. Chem. 38:309-376, 2001); O'Brien et al. (2001) Isothermal
      titration calorimetry of biomolecules. In: Harding, S. E. and Chowdhry, B. Z.
      (eds.), Protein-Ligand Interactions: Hydrodynamics and Calorimetry, A Practical
      Approach. Oxford University Press, Oxford, UK] and differential scanning
      calorimetry [Jelesarov and Bosshard (J. Mol. Recognit. 12:3-18, 1999); Privalov
      and Dragan (Biophys. Chem. 126:16-24, 2007); Cooper et al. (2001) Differential
      scanning microcalorimetry. In: Harding, S. E. and Chowdhry, B. Z. (eds.), Protein
      Ligand Interactions: Hydrodynamics and Calorimetry, A Practical Approach. Oxford
      University Press, Oxford, UK] are valuable tools for characterising protein
      targets, and their interactions with ligands, during the drug discovery process.
      The parameters obtained from these techniques: triangle DeltaH, triangle DeltaG,
      triangle DeltaS, and triangle DeltaC (p), are properties of the entire system
      studied and may be composed of many contributions, including the binding reaction
      itself, conformational changes of the protein and/or ligand during complexation,
      changes in solvent organisation or other equilibria linked to the binding
      process. Dissecting and understanding these components, and how they contribute
      to binding interactions, is a critical step in the ability to design ligands that
      have high binding affinity for the target protein.

PMID- 20694689
TI  - Adaptive combinatorial design of focused compound libraries.
AB  - Low-throughput screening for bioactive substances often represents the only way
      to discover new ligands of a drug target. This limits the number of compounds
      that can be tested for bioactivity. In such a situation, the design of small,
      focused compound libraries provides an alternative to the concept of large,
      maximally diverse screening collections. We present the technique of "adaptive"
      compound library design, which implements a simulated evolutionary process.
      Compound assembly and determination of bioactivity can be performed using
      computer-based methods (virtual screening), or in the laboratory. We show that
      there exists an optimal combination of the size of a screening library and the
      number of iterative screening rounds with the aim to keep experimental efforts at
      a minimum.

PMID- 20694690
TI  - Chemical microarrays: a new tool for discovery enzyme inhibitors.
AB  - Enzymes, the catalytic proteins, are playing pivotal roles in regulating basic
      cell functions. Drugs that inhibit enzyme activities cover varying aspects of
      diseases and offer potential cures. One of the major technologies used in the
      drug discovery industry for finding the enzyme inhibitors is high-throughput
      screening, which is facing a daunting challenge due to the fast-growing numbers
      of drug targets arising from genomic and proteomic research and the large
      chemical libraries generated from high-throughput synthesis. Chemical microarray,
      as a new technology, could be an excellent alternative for traditional well-based
      screening, since the technology can screen more compounds against more targets in
      parallel with a minimum amount of materials, reducing cost and increasing
      productivity. In this chapter, we have introduced the basic techniques and
      applications of chemical microarrays, and how to use them routinely for
      identifying enzyme inhibitors with functional-based assays. Sample assays for
      kinases, proteases, histone deacetylases, and phosphatases are demonstrated.

PMID- 20694691
TI  - Fluorescence polarization and time-resolved fluorescence resonance energy
      transfer techniques for PI3K assays.
AB  - Fluorescence-based biochemical assays are sensitive and convenient to use;
      therefore, they are widely employed for enzyme assays and molecular interaction
      studies. However, when this method is applied for screening of a compound library
      for drug discovery, high fluorescence compounds, which usually exist in large
      numbers in chemical libraries, are problematic. Fluorescence Polarization (FP)
      and Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) assays are
      less affected by compound fluorescence and suitable for large-scale high
      throughput screening (HTS). In this section, we describe homogenous FP and TR
      FRET methods for PI3-kinase (PI3K), a family of lipid kinases that is "difficult
      to-do-HTS" since traditional radioisotope assays are hard to apply to HTS format.
      The application of FP and TR-FRET techniques for PI3K HTS will be described and
      advantages and disadvantages of these assays will be discussed.

PMID- 20694692
TI  - Small molecule protein interaction profiling with functional protein microarrays.
AB  - Small molecules possess the ability to interact with proteins and perturb their
      specific functions, a property that has been exploited for numerous research
      applications and to produce therapeutic agents in disease treatment. However,
      commonly utilized mass spectrometry-based approaches for identifying the target
      proteins for a small molecule have a number of limitations, particularly in terms
      of throughput and time and resource consumption. In addition, current
      technologies lack a mechanism to broadly assess the selectivity profile of the
      small molecule, which may be important for understanding off-target effects of
      the compound. Protein microarray technology has emerged as a powerful tool in the
      systems biology arsenal. Here, we describe how protein microarray technology can
      be applied to the study of small molecule protein interactions, with sensitivity
      sufficient to detect interactions with low muM affinity. These assays are highly
      reproducible, sensitive, and scalable, and provide an enabling technology for
      small molecule selectivity profiling in the context of drug development.

PMID- 20694693
TI  - Capillary electrophoresis in drug discovery.
AB  - The several advantages that capillary electrophoresis (CE) offers in the study of
      protein folding, protein-ligand and protein-protein interactions, render this
      methodology appealing in several areas. In this chapter, a specific example is
      reported, where the use of affinity CE (ACE) in drug discovery is particularly
      advantageous over other separative and spectroscopic techniques. ACE is an
      analytical approach in which the migration patterns of interacting molecules in
      an electric field are recorded and used to identify specific binding and to
      estimate binding constants. A library of compounds has been tested, in free
      solution and with minimum sample consumption, for the affinity to two targets
      previously separated by CE, the native form and the partially structured
      intermediate of the folding of beta(2)-microglobulin (beta(2)-m) [Chiti et al.
      (J. Biol. Chem. 276:46714-46721, 2001), Quaglia et al. (Electrophoresis 26:4055
      4063, 2005)]. beta(2)-m is an intrinsically amyloidogenic protein, and its
      tendency to misfold is responsible for dialysis-related amyloidosis, an
      unavoidable complication of chronic haemodialysed patients. The criteria for
      choosing the compounds to be screened, the method conditions, and the possible
      data analysis strategies are detailed and discussed in this chapter.

PMID- 20694694
TI  - SPR in drug discovery: searching bioactive compounds in plant extracts.
AB  - Biosensors represent an interesting tool in the search of bioactive compounds. In
      particular, optical sensors based on Surface Plasmon Resonance transduction (SPR)
      allow monitoring of biomolecular interaction in real time and without any
      labelling of the interactants. The biosensor analysis can be applied to both pure
      compounds or to complex mixtures (e.g. plant extract). The SPR detection
      principle is here presented and the application to the analysis of plant extracts
      (i.e. of Chelidonium majus L.) as a paradigmatic example for the search of
      bioactive compounds able to interact with DNA, is also discussed.

PMID- 20694695
TI  - Application of frontal affinity chromatography with mass spectrometry (FAC-MS)
      for stereospecific ligand-macromolecule interaction, detection and screening.
AB  - Using frontal affinity chromatography coupled to mass spectrometry (FAC-MS) we
      have established a general stereoselective detection and screening method of
      intact racemates which can generate binding affinity information about the
      individual enantiomers that is also applicable to other ligand isomeric mixtures.
      FAC-MS has been shown to be a versatile technology utilizing direct binding in
      screening assays and extending its application toward chiral drug development,
      especially in the early discovery stages as well as its utility in secondary
      Structure-activity relationship (SAR) studies allow this platform to make a
      significant step toward facilitating the demand for pure enantiomeric drugs.
      Using renin, which is as an important drug target, we show that for detection and
      screening purposes there is no need to first use timely and costly methods of
      separating racemates in order to get precise information about the binding
      affinities of the composite enantiomers.

PMID- 20694696
TI  - GPC spin column HPLC-ESI-MS methods for screening drugs noncovalently bound to
      proteins.
AB  - Secondary drug screening methods are described for determining the relative
      degree of non-covalent binding between drug candidates and a protein of
      therapeutic interest by gel centrifugation chromatography using GPC spin columns
      for isolating the protein-drug complexes, under native conditions, and reversed
      phase HPLC coupled with ESI-MS for highly resolved and sensitive detection of the
      drug in the complex, under denaturing conditions. The necessary control samples
      and limitations of this work are fully described. The GPC spin column HPLC-ESI-MS
      methodology for screening of drugs non-covalently bound to proteins is
      illustrated for the non-covalent binding of geldanamycin with Hsp90cat protein.

PMID- 20694697
TI  - A scintillation proximity assay for fatty acid amide hydrolase compatible with
      inhibitor screening.
AB  - Scintillation proximity assay (SPA) is a homogenous and versatile technology for
      the simple and sensitive detection of the interaction of protein targets with
      their ligands. Herein, we described a SPA assay developed to identify compounds
      that bind to human fatty acid amide hydrolase (FAAH). This SPA assay utilizes the
      specific binding of [(3)H]-R(+)-methanandamide ((3)H-MAEA), a competitive
      nonhydrolyzed FAAH inhibitor, to FAAH expressing microsomes and evaluates its
      displacement by FAAH inhibitors. In contrast to the classical SPA radioligand
      binding assay which detects bound ligand, in our assay the released radiolabel is
      detected through its interaction with the SPA beads. This novel SPA assay has
      been validated and demonstrated to be simple, sensitive, and amenable to high
      throughput screening.

PMID- 20694698
TI  - A natural products approach to drug discovery: probing modes of action of
      antitumor agents by genome-scale cDNA library screening.
AB  - In the last few years, genomic tools have been incorporated in natural product
      approaches to drug discovery, including understanding mechanisms of action which
      cannot be elucidated from phenotypic screens such as cell viability assays. The
      characterization of perturbed biological pathways and target identification are
      important for the evaluation of the compounds' potential as drug leads and for
      subsequent medicinal chemistry efforts; however, general procedures to tackle
      this task are lacking. The combination of high-throughput screening and genomic
      scale assays has proven to be a powerful tool to aid in the identification of
      mechanisms and potentially of protein targets, not only in yeast but also
      mammalian cells. Arrayed libraries of cDNAs can be transfected into cancer cell
      lines in a high-throughput fashion to generate variants of spatially separated
      cancer cells with increased gene dosages for one particular cDNA. Cells
      overexpressing gene products that are directly targeted by a small molecule or
      that lie in the perturbed pathway may be less susceptible to the effects of the
      compound. This fact provides the basis for drug susceptibility screens employing
      cDNA libraries. The general procedures to optimize and execute those screens and
      subsequently validate putative screening hits are discussed in detail.

PMID- 20694699
TI  - Ligand-macromolecule interactions in live cells by fluorescence correlation
      spectroscopy.
AB  - The receptor concept is the primary theoretical basis for modern pharmacology.
      Drugs, hormones, neurotransmitters, toxin, and other biologically active
      substances are referred to as ligands. Ligands exert their actions by way of
      interaction with receptors/macromolecules. The resulting receptor/macromolecule
      ligand complexes produce alterations in physiological processes.
      Receptor/macromolecule-binding studies most often require the use of
      radioactively labeled ligands. When the numbers of receptors/macromolecules are
      few per cell, it is impossible to detect the specific binding because of a high
      background. Specific interactions between certain ligands and their
      receptors/macromolecules are, therefore, often overlooked by the conventional
      binding technique. Fluorescence correlation spectroscopy (FCS) allows detection a
      ligand-macromolecule interaction in live cells in a tiny confocal volume element
      (0.2 femtoliter (fL)) at single-molecule detection sensitivity. FCS permits the
      identification of macromolecules that were not possible to detect before by
      isotope labeling. The beauty of the FCS technique is that there is no need for
      separating an unbound ligand from a bound one to calculate the macromolecule
      bound and free ligand fractions. This study will demonstrate FCS as a sensitive
      and a rapid technique to study ligand-macromolecule interaction in live cells
      using fluorescently labeled ligands (Fl-L). This study is of pharmaceutical
      significance since FCS assay of ligand-macromolecule interactions in live cells
      is one step forward toward a high throughput drug screening in cell cultures.

PMID- 20694712
TI  - [Treatment of polytrauma in the intensive care unit].
AB  - The treatment of severely injured trauma patients (polytrauma) is one of the
      outstanding challenges in medical care. Early in the initial course the patient's
      diagnostics have to be scrupulously reevaluated by an interdisciplinary team
      (tertiary trauma survey) to reduce deleterious sequelae of missed injuries after
      the initial assessment. Severely injured patients stay in intensive care for an
      average of 11 days. During this time the patient's therapy has to ensure a high
      quality evidence-based intensive care treatment and simultaneously has to be
      tailored to the current individual injuries. Because of the fact that the damage
      control strategy is gaining increasing acceptance, the intensive care unit plays
      a pivotal role in the critical time between emergency and elective surgery.
      Therefore a close cooperation between physicians of the intensive care unit and
      all surgical disciplines involved is essential to reach the aim of therapeutic
      efforts. After survival of emergency treatment patients with severe trauma should
      be reintegrated into social and occupational life as soon as possible.

PMID- 20694713
TI  - [Acute renal failure and sepsis : Just an organ dysfunction due to septic
      multiorgan failure?].
AB  - Acute renal failure (ARF) is clinically defined as an abrupt, but in principle
      reversible deterioration of glomerular and tubular function. Regarding
      pathophysiology, ARF is caused by ischemic renal conditions and toxic mediators.
      Sepsis is the most common cause of ARF in the intensive care unit and ARF is an
      independent risk factor for lethality of septic patients. Interventions to
      protect the kidneys against ARF include preliminary optimization of renal
      perfusion by volume load with cristalloid solutions and the administration of
      vasopressors. Daily maximum permissible dosages for colloids should not be
      exceeded and hyperoncotic colloid solutions should be generally avoided. Dopamine
      in "renal dosage" is nowadays obsolete. Loop diuretics produce diuresis and can
      be beneficial to extrarenal organs by improving fluid homeostasis, however
      diuretics do not improve kidney function and outcome. Therefore, diuretics are
      not indicated for patients with imminent or existing ARF. Septic patients with
      ARF can be treated by intermittent and continuous forms of renal replacement
      therapy, whereas continuous convective and intermittent diffusive methods are
      equivalent when utilizing an ultrafiltration rate > or =20 ml/h*kg body weight or
      a therapeutic interval > or =3 times/week.

PMID- 20694714
TI  - [Minimal provider volume in total knee replacement : an analysis of the external
      quality assurance program of North Rhine-Westphalia (QS-NRW)].
AB  - BACKGROUND: A minimal provider volume for total knee replacement (TKR) was
      introduced in 2006. Does this lead to an improvenment in quality or not? The
      records of treatment in the compulsory external quality assurance program of the
      Land of North Rhine-Westphalia (QS-NRW) were evaluated. METHOD: A total of
      125,324 comparable records from the QS-NRW program were available to determine
      the appearance of general and surgical complications. In a logistical regression
      model the risk factors age, gender, ASA classification, comorbidity and duration
      were taken into account. RESULTS: A significant reduction could only be shown for
      pneumonia, thrombotic events and lung embolisms as well as vascular injury. In
      2006 and 2007 malpositioning of implants was significantly higher and from 2005
      to 2008 the number of fractures rose compared to 2004. Deep infections and
      reoperations did not change significantly during the whole study period.
      CONCLUSION: This evaluation could not show an improvement in quality due to the
      minimal provider volume. Thus the minimal provider volume should not be taken
      into account as a main criterion to improve quality. Further outcome studies and
      creating an arthroplasty register in Germany are more useful.

PMID- 20694715
TI  - [Living donation liver transplantation in children].
AB  - Liver transplantation is the first-line therapy for children with acute and
      chronic hepatic failure, metabolic liver diseases and liver tumors. As most of
      the children with end-stage liver disease are very small in stature the resources
      of compatible organs of deceased donors are limited. Living liver donation was
      able to nearly eliminate waiting list mortality with excellent patient and graft
      survival. As 80% of the pediatric recipients have a body weight <25 kg donation
      of the left lateral lobe (segments II+III) is sufficient in most of the cases.
      According to a standardization of the surgical procedures as well as the
      preoperative, intraoperative and postoperative management donation of the left
      lateral lobe advanced to a procedure with very low donor morbidity and mortality
      rates. The complexity of hepatic disease patterns in pediatric patients which
      often affect other organ systems demand a close cooperation with an experienced
      pediatric team. Pediatric living donor liver transplantation requires high
      expertise in liver surgery and split liver transplantation and should therefore
      only be performed in transplant centers meeting these high qualifications.

PMID- 20694716
TI  - [Heparin-induced thrombocytopenia].
AB  - Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction that carries
      an increased risk of thromboembolic complications. HIT is caused by platelet
      activating antibodies directed against a complex of platelet factor 4 (PF4) and
      heparin. HIT typically manifests in the second week after initiation of heparin
      therapy with a platelet count reduction of more than 50% of the highest level
      after the start of heparin administration as well as thromboembolic events. The
      clinical probability can be calculated by the 4 T's score. The laboratory
      diagnosis of HIT is based on confirmation of PF4/heparin antibodies or on
      functional tests that provide evidence of heparin-dependent platelet-activating
      antibodies. A low 4 T's score and negative HIT test virtually rule out the
      presence of HIT. Patients with acute HIT require anticoagulation with a
      compatible anticoagulant in a therapeutic dose. The drugs currently available for
      this include the direct thrombin inhibitors argatroban, lepirudin, bivalirudin,
      and desirudin and the indirect factor Xa inhibitors danaparoid and fondaparinux.

PMID- 20694717
TI  - [Presacral schwannoma with degenerated areas ("ancient schwannoma")].
AB  - A presacral, degenerative schwannoma ("ancient schwannoma") is a rare entity. The
      clinical signs are nonspecific, and a reliable preoperative diagnosis is
      difficult. Tumor heterogeneity with calcifications may be seen in degenerated
      schwannomas on MRI or CT but not necessarily. First-line treatment is complete
      surgical excision. We present the case of a 44-year-old male who required surgery
      for a presacral mass. Histopathological examination revealed the diagnosis of a
      schwannoma with degenerated areas.

PMID- 20694718
TI  - A mutation in KCNJ11 causing human hyperinsulinism (Y12X) results in a glucose
      intolerant phenotype in the mouse.
AB  - AIMS/HYPOTHESIS: We identified a mouse with a point mutation (Y12STOP) in the
      Kcnj11 subunit of the K(ATP) channel. This point mutation is identical to that
      found in a patient with congenital hyperinsulinism of infancy (HI). We aimed to
      characterise the phenotype arising from this loss-of-function mutation and to
      compare it with that of other mouse models and patients with HI. METHODS: We
      phenotyped an N-ethyl-N-nitrosourea-induced mutation on a C3H/HeH background
      (Kcnj11 ( Y12STOP )) using intraperitoneal glucose tolerance testing to measure
      glucose and insulin plasma concentrations. Insulin secretion and response to
      incretins were measured on isolated islets. RESULTS: Homozygous male and female
      adult Kcnj11 ( Y12STOP ) mice exhibited impaired glucose tolerance and a defect
      in insulin secretion as measured in vivo and in vitro. Islets had an impaired
      incretin response and reduced insulin content. CONCLUSIONS/INTERPRETATION: The
      phenotype of homozygous Kcnj11 ( Y12STOP ) mice is consistent with that of other
      Kcnj11-knockout mouse models. In contrast to the patient carrying this mutation
      homozygously, the mice studied did not have hyperinsulinaemia or hypoglycaemia.
      It has been reported that HI patients may develop diabetes and our mouse model
      may reflect this clinical feature. The Kcnj11 ( Y12STOP ) model may thus be
      useful in further studies of K(ATP) channel function in various cell types and in
      investigation of the development of hyperglycaemia in HI patients.

PMID- 20694719
TI  - Kosmotoga arenicorallina sp. nov. a thermophilic and obligately anaerobic
      heterotroph isolated from a shallow hydrothermal system occurring within a coral
      reef, southern part of the Yaeyama Archipelago, Japan, reclassification of
      Thermococcoides shengliensis as Kosmotoga shengliensis comb. nov., and emended
      description of the genus Kosmotoga.
AB  - A novel thermophilic and sulfur-reducing bacterium, strain S304(T), was isolated
      from the Taketomi submarine hot spring shallow hydrothermal field located at
      southern part of the Yaeyama Archipelago, Japan. The cells were non-motile short
      thick rods or oval cocci 1.1-2.7 MUm in length and 1.1-1.9 MUm in width. Strain
      S304(T) was an obligately anaerobic heterotroph and sulfur reduction stimulates
      growth. Growth was observed between 50-65 degrees C (optimum 60 degrees C), pH
      6.2-8.0 (optimum pH 7.1), 1.0-6.0% NaCl concentration (optimum 3.0%). The fatty
      acid composition was C(16:0) (71.4%), C(18:0) (20.9%) and C(18:1) (7.7%). The G +
      C content of genomic DNA was 40.8 mol%. The 16S rRNA gene sequence analysis
      indicated that strain S304(T) belonged to the genus Kosmotoga. Based on
      physiological and phylogenetic features of a new isolate, we propose new species
      in the genus Kosmotoga: the type strain of Kosmotoga arenicorallina sp. nov is
      S304(T) (=JCM 15790(T) = DSM22549(T)). Thermococcoides shengliensis 2SM-2(T) is
      phylogenetically associated with Kosmotoga olearia 14.5.1(T). Based on the
      phylogenetic relationship between Thermococcoides shengliensis 2SM-2(T) and
      Kosmotoga olearia 14.5.1(T), we propose the reclassification of Thermococcoides
      shengliensis as Kosmotoga shengliensis comb. nov. (type strain 2SM-2(T)). In
      addition, an emended description of the genus Kosmotoga is proposed.

PMID- 20694720
TI  - Stability assessment of gas mixtures containing terpenes at nominal 5 nmol/mol
      contained in treated aluminum gas cylinders.
AB  - Studies of climate change increasingly recognize the diverse influences exerted
      by terpenes in the atmosphere, including roles in particulates, ozone formation,
      and their oxidizing potential. Measurements of key terpenes suggest atmospheric
      concentrations ranging from low pmol/mol (parts per trillion) to nmol/mol (parts
      per billion), depending on location and compound. To accurately establish
      concentration trends, assess the role of terpenes in atmospheric chemistry, and
      relate measurement records from many laboratories and researchers, it is
      essential to have good calibration standards. The feasibility of preparing well
      characterized, stable gas cylinder standards for terpenes at the nmol/mol level
      is not yet well established. Several of the world's National Metrology Institutes
      (NMIs) are researching the feasibility of developing primary and secondary
      reference gas standards at the nmol/mol level for terpenes. The US NMI, the
      National Institute of Standards and Technology, has prepared several nmol/mol
      mixtures, in treated aluminum gas cylinders, containing terpenes in dry nitrogen
      at nominal 5 nmol/mol for stability studies. Overall, 11 terpenes were studied
      for stability. An initial gas mixture containing nine terpenes, one oxygenate,
      and six aromatic compounds, including benzene as an internal standard, was
      prepared. Results for four of the nine terpenes in this initial mixture indicate
      stability in these treated aluminum gas cylinders for over 6 months and project
      long term (years) stability. Interesting results were seen for beta-pinene, which
      when using a linear equation rate decline predicts that it will reach a zero
      concentration level at day 416. At the same time, increases in alpha-pinene, D: 
      limonene (R-(+)-limonene), and p-cymene were observed, including camphene, a
      terpene not prepared in the gas mixture, indicating a chemical transformation of
      beta-pinene to these species. Additional mixtures containing combination of
      either alpha-pinene, camphor, alpha-terpinene, and benzene indicate a second
      order quadratic rate decline for the alpha-pinene and alpha-terpinene, a linear
      rate decline for camphor, and a second-order quadratic rate increase of camphene.

PMID- 20694721
TI  - A novel FRET approach for in situ investigation of cellulase-cellulose
      interaction.
AB  - A novel real-time in situ detection method for the investigation of cellulase
      cellulose interactions based on fluorescence resonance energy transfer (FRET) has
      been developed. FRET has been widely used in biological and biophysical fields
      for studies related to proteins, nucleic acids, and small biological molecules.
      Here, we report the efficient labeling of carboxymethyl cellulose (CMC) with
      donor dye 5-(aminomethyl)fluorescein and its use as a donor in a FRET assay
      together with an Alexa Fluor 594 (AF594, acceptor)-cellulase conjugate as
      acceptor. This methodology was successfully employed to investigate the
      temperature dependency of cellulase binding to cellulose at a molecular level by
      monitoring the fluorescence emission change of donor (or acceptor) in a
      homogeneous liquid environment. It also provides a sound base for ongoing
      cellulase-cellulose study using cellulosic fiber.

PMID- 20694722
TI  - Detection of quorum sensing molecules in Burkholderia cepacia culture
      supernatants with enzyme-linked immunosorbent assays.
AB  - The Burkholderia cepacia complex (Bcc) employs a quorum sensing (QS) mechanism
      which is a cell density-dependent bacterial communication system to regulate
      certain gene expressions. As with many other Gram-negative bacteria, Burkholderia
      cepacia species use (N-acyl-)homoserine lactones (AHLs or HSLs) as signalling
      molecules. Because of the essential role of QS in bacterial behavior, the aim of
      this study was to demonstrate the applicability of our in-house-developed enzyme
      linked immunosorbent assays (ELISAs) for the detection of bacterial activities
      via HSLs in B. cepacia strain LA3 culture supernatants. For this purpose the
      previously developed monoclonal antibodies (mAbs) HSL1/2-2C10 and HSL1/2-4H5 were
      exploited. N-3-Oxo-decanoyl-L-homoserine lactone (3-oxo-C10-HSL) was used as main
      analyte throughout all experiments. With the bacterial culture medium (named ABC
      medium) a matrix effect in both ELISAs was visible (slight increase in optical
      density, shift in test midpoints (IC(50)) and working ranges). For example, ELISA
      with mAb HSL1/2-2C10 and enzyme tracer HSL3-HRP (HSL derivative conjugated to
      horseradish peroxidase) had an IC(50) of 120 MUg L(-1) for 3-oxo-C10-HSL in
      phosphate-buffered saline versus 372 MUg L(-1) in ABC medium. A significant
      increase of HSLs in B. cepacia strain LA3 culture supernatants after 12 h to 48 h
      of growth was observed. Although the analytical result of these immunoassays
      cannot distinguish HSLs from homoserines (HSs), the appearance of these compounds
      can be easily followed. Hydrolysis and spiking experiments were carried out with
      these biological samples. According to our knowledge, these are the first
      immunoassays for the detection of quorum sensing molecules in biological culture
      supernatants. This study provides a cost-effective, fast, and sensitive
      analytical method for detection of HSLs/HSs in biological samples without complex
      sample preparation and will offer a quick idea about B. cepacia activities. The
      low sample amount requirement (less than 1 mL) constitutes a tremendous advantage
      for many analytical questions with biological samples.

PMID- 20694723
TI  - Cutaneous silent period in human FDI motor units.
AB  - In this study, we aimed to use both the probability-based and the frequency-based
      analyses methods simultaneously to examine cutaneous silent period (CSP) induced
      by strong electrical currents. Subjects were asked to contract their first dorsal
      interosseus muscles so that one motor unit monitored via intramuscular wire
      electrodes discharged at a rate of approximately 8 Hz. Strong electrical stimuli
      were delivered to the back of the hand that created a subjective discomfort level
      of between 4 and 7 [0-10 visual analogue scale] and induced cutaneous silent
      period in all units. It was found that the duration of the CSP was significantly
      longer when the same data were analysed using frequency-based analysis method
      compared with the probability-based methods. Frequency-based analysis indicated
      that the strong electrical stimuli induce longer lasting inhibitory currents than
      what was indicated using the probability-based analyses such as surface
      electromyogram and peristimulus time histogram. Usage of frequency-based analysis
      for bringing out the synaptic activity underlying CSP seems essential as its
      characteristics have been subject to a large number of studies in experimental
      and clinical settings.

PMID- 20694724
TI  - Osteoid osteoma of the femur in a 7-month-old infant treated with radiofrequency
      ablation.
AB  - Osteoid osteoma occurs most commonly in children, adolescents, and young adults
      between the ages of 5 and 30 years. In the preschool age group, it is quite
      uncommon, accounting for only 3-8% of all osteoid osteoma cases. We report a case
      of osteoid osteoma in a 7-month-old infant, who presented with decreased use of
      the right lower extremity due to pain. Magnetic resonance imaging (MRI) showed an
      atypical appearance. A biopsy of the lesion, with histopathological examination,
      confirmed the diagnosis of osteoid osteoma. Radiofrequency ablation (RFA) of the
      nidus under computed tomography (CT) guidance was performed. The patient
      developed a recurrence after 3 months, which was treated with a second RFA. On
      subsequent follow-up, the infant did not show signs of pain after 1 month. In
      summary, this case report shows that osteoid osteoma can present in early infancy
      and can be successfully treated with RFA at this age, however, recurrence after
      the procedure can occur and close follow-up is recommended.

PMID- 20694725
TI  - Significance of clinical and radiographic findings in young adults after slipped
      capital femoral epiphysis.
AB  - The purpose of this study was to assess the clinical and radiographic
      presentation of young adults in the mid-term follow-up after pinning in situ for
      mild to moderate slipped capital femoral epiphysis (SCFE). We postulated that
      there was a correlation between the degree of head-neck-offset decrease and
      clinical and radiographic signs of hip joint degeneration. Thirty-eight young
      adults (average age 23.4 +/- 3.6 years old) with various grades of femoral head
      neck-offset pathologies were assessed clinically via Harris hip score (HHS),
      Tegner-Lysholm score (TLS) and Short Form 36 (SF-36), and radiographic signs of
      OA were measured on plain X-ray films after a follow-up of 11.1 +/- 3.8 years. We
      conclude that clinical and radiographic signs of joint degeneration appear early
      in the follow-up after SCFE, but there is no linear correlation between offset
      pathology and joint degeneration.

PMID- 20694726
TI  - Ascorbate exerts anti-proliferative effects through cell cycle inhibition and
      sensitizes tumor cells towards cytostatic drugs.
AB  - PURPOSE: While the benefits of ascorbic acid (vitamin C, ascorbate) as an
      essential nutrient are well established, its effects on tumor cells and in tumor
      treatment are controversial. In particular, conflicting data exist whether
      ascorbate may increase the cytotoxic effects of antineoplastic drugs or may
      rather exert adverse effects on drug sensitivity during cancer treatment.
      Findings are further obscured regarding the distinction between ascorbate and
      dehydroascorbate (DHA). Thus, the purpose of this study was to evaluate and
      directly compare the cytotoxic efficacy of ascorbate compared to DHA, and to
      analyse if ascorbate at pharmacological concentrations affects the efficacy of
      antineoplastic agents in prostate carcinoma cells. METHODS: We directly compare
      the effects of ascorbate (supplied as 'Pascorbin solution for injection') and DHA
      on tumor cell viability, and determine IC(50) values for various cell lines. At
      concentrations well below the IC(50), ascorbate effects on cell proliferation and
      cell cycle are analysed. We furthermore determine changes in cellular sensitivity
      towards various cytostatic drugs upon pre-treatment of cells with ascorbate.
      RESULTS: We demonstrate higher therapeutic efficacy of ascorbate over DHA in
      various cell lines, independent of cell line-specific differences in ascorbate
      sensitivity, and identify the extracellular generation of H(2)O(2) as critical
      mechanism of ascorbate action. We furthermore show that, in addition to pro
      apoptotic effects described previously, ascorbate treatment already at
      concentrations well below the IC(50) exerts anti-proliferative effects on tumor
      cells. Those are based on interference with the cell cycle, namely by inducing a
      G(0)/G(1) arrest. Pre-treatment of tumor cells with ascorbate leads to increased
      cellular sensitivity towards Docetaxel, Epirubicin, Irinotecan and 5-FU, but not
      towards Oxaliplatin and Vinorelbin. For Docetaxel and 5-FU, a linear correlation
      between this sensitizing effect and the ascorbate dosage is observed.
      CONCLUSIONS: The redox-active form of vitamin C, ascorbate, shows therapeutic
      efficacy in tumor cells. These antitumor effects of ascorbate are mainly based on
      its extracellular action and, in addition to the induction of apoptosis, also
      include an anti-proliferative effect by inducing cell cycle arrest. Furthermore,
      ascorbate treatment specifically enhances the cytostatic potency of certain
      chemotherapeutics, which implicates therapeutic benefit during tumor treatment.

PMID- 20694728
TI  - [Femtosecond lenticule extraction (FLEx)].
AB  - Starting in 2006 a new "all femto" method of refractive correction for myopia and
      myopic astigmatism was introduced. This new method was originally introduced as
      femtosecond lenticule extraction (FLEx) and further developed with a small
      incision into SMILE (small incision lenticule extraction). To simplify the
      terminology the manufacturer brought this onto the market in April 2010 as ReLEx
      (refractive lenticule extraction). In this procedure a lenticule of intrastromal
      corneal tissue and a flap-like access cut are subsequently cut utilizing the
      VisuMax(r) femtosecond system (Carl Zeiss Meditec, Jena, Germany). The lenticule
      is then manually removed and the flap repositioned (only by FLEx). In
      approximately 1,000 successful surgical operations only few side effects were
      found. The number of eyes treated is currently being expanded in order to further
      standardize this new clinical procedure.

PMID- 20694727
TI  - A Phase 1 study of UCN-01 in combination with irinotecan in patients with
      resistant solid tumor malignancies.
AB  - PURPOSE: UCN-01 (7-hydroxystaurosporine) is a multi-targeted protein kinase
      inhibitor that exhibits synergistic activity with DNA-damaging agents in
      preclinical studies. We conducted a Phase I study to determine the maximum
      tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetic, and
      pharmacodynamic effects of UCN-01 and irinotecan in patients with resistant solid
      tumors. EXPERIMENTAL DESIGN: Patients received irinotecan (75-125 mg/m(2) IV on
      days 1, 8, 15, 22) and UCN-01 (50-90 mg/m(2) IV on day 2 and 25-45 mg/m(2) on day
      23 and subsequent doses) every 42 days. Blood for pharmacokinetics of UCN-01 and
      irinotecan, and blood, normal rectal mucosa, and tumor biopsies for
      pharmacodynamic studies were obtained. RESULTS: Twenty-five patients enrolled to
      5 dose levels. The MTD was irinotecan 125 mg/m(2) on days 1, 8, 15, 22 and UCN-01
      70 mg/m(2) on day 2 and 35 mg/m(2) on day 23. DLTs included grade 3
      diarrhea/dehydration and dyspnea. UCN-01 had a prolonged half-life and a low
      clearance rate. There was a significant reduction in SN-38 C(max) and
      aminopentanocarboxylic acid (APC) and SN-38 glucuronide half-lives.
      Phosphorylated ribosomal protein S6 was reduced in blood, normal rectal mucosa,
      and tumor biopsies at 24 h post-UCN-01. Two partial responses were observed in
      women with ER, PgR, and HER2-negative breast cancers (TBNC). Both tumors were
      defective for p53. Twelve patients had stable disease (mean duration 18 weeks,
      range 7-30 weeks). CONCLUSION: UCN-01 and irinotecan demonstrated acceptable
      toxicity and target inhibition. Anti-tumor activity was observed and a study of
      this combination in women with TNBC is underway.

PMID- 20694729
TI  - [Rituximab].
AB  - Rituximab as a monoclonal antibody against CD20 was approved for treatment of
      patients with rheumatoid arthritis (RA) with inadequate response to or
      contraindication for the use of a TNF blocker. This article focuses on current
      results from clinical trials at different developmental stages as well as from
      registry data in anti-TNF non-responders regarding the documented efficacy with
      respect to RA activity, radiological progression and improvement of functional
      indices. The available safety data for rituximab for this particular indication
      showed that the overall risk of infection, including severe manifestations, is
      not further increased. The occurrence of progressive multifocal
      leukoencephalopathy (PML) after rituximab requires further observation; the risk
      has currently been estimated at about 1:15.000-20.000 of RA patients treated. Of
      relevance, decreased IgG levels prior to treatment have been reported to be
      associated with a substantially increased risk for infections, and therefore, in
      such cases other treatment options should be considered.

PMID- 20694730
TI  - A survey of metastatic central nervous system tumors to cervical lymph nodes.
AB  - In the realm of head and neck diseases, one particularly common clinical
      presentation is that of the patient with a cervical mass. In children, neck
      masses often prove to be developmental cysts; in adults, the recent onset of a
      neck mass can signal a metastasis from a head and neck squamous carcinoma. Less
      often, both adults and children may present with cervical masses caused by either
      non-Hodgkin's lymphoma or Hodgkin's disease. There are, of course, less
      frequently encountered differential diagnostic possibilities; one of the most
      uncommon of all is the possibility of metastasis from an intracranial tumor.
      Intracranial tumors rarely give rise to cervical node metastases. The present
      review examines the published experience with 128 tumors that gave rise to
      cervical node metastases in both adult and in pediatric patients. While it is
      presumed that the blood-brain barrier blocks the spread of most tumors beyond the
      intracranial locale, this is speculative. Although many of the cervical node
      metastases reported here arose after craniotomy (and, presumably, after breaching
      of the blood-brain barrier), some arose in the absence of any preceding surgical
      procedure. Cervical node metastases may arise from glial tumors (including
      glioblastoma multiforme, in both adult and pediatric patients) and non-glial
      tumors (such as medulloblastoma in pediatric patients). The history of a previous
      intracranial lesion is often the key to correct diagnosis, since, without
      prompting, neither the pathologist nor the radiologist is likely to think of a
      cervical node metastasis from a brain tumor when assessing a cervical mass of
      unknown etiology.

PMID- 20694731
TI  - Practical neck cooling and time-trial running performance in a hot environment.
AB  - The aim of this two-part experiment was to investigate the effect of cooling the
      neck on time-trial performance in hot conditions (~30 degrees C; 50% RH). In
      Study A, nine participants completed a 75-min submaximal (~60% V(O2(max)) pre
      load phase followed by a 15-min self-paced time-trial (TT) on three occasions:
      one with a cooling collar (CC(90)), one without a collar (NC(90)) and one with
      the collar uncooled (C(90)). In Study B, eight participants completed a 15-min TT
      twice: once with (CC(15)) and once without (NC(15)) a cooling collar. Time-trial
      performance was significantly improved in Study A in CC(90) (3,030 +/- 485 m)
      compared to C(90) (2,741 +/- 537 m; P = 0.008) and NC(90) (2,884 +/- 571 m; P =
      0.041). Fifteen-minute TT performance was unaffected by the collar in Study B
      (CC(15) = 3,239 +/- 267 m; NC(15) = 3,180 +/- 271 m; P = 0.351). The collar had
      no effect on rectal temperature, heart rate or RPE. There was no effect of
      cooling the neck on S100beta, cortisol, prolactin, adrenaline, noradrenaline or
      dopamine concentrations in Study A. Cooling the neck via a cooling collar can
      improve exercise performance in a hot environment but it appears that there may
      be a thermal strain threshold which must be breached to gain a performance
      benefit from the collar.

PMID- 20694732
TI  - Proposal for modification of the ENSAT staging system for adrenocortical
      carcinoma using tumor grade.
AB  - PURPOSE: Various staging systems for adrenocortical carcinoma (ACC) have been
      proposed. We hypothesized that incorporating tumor grade into the current
      European Network for the Study of Adrenal Tumors (ENSAT) staging system would
      improve the ability to more accurately predict time to recurrence and death.
      METHODS: A retrospective review of patients included in the University of
      Michigan ACC database from 2005 to 2009 was done; and stage, tumor grade, time to
      recurrence, and death were recorded and analyzed using the Cox regression and
      Kaplan-Meier survival curves. RESULTS: Ninety one patients had complete
      information for inclusion. The median follow-up was 24 months while the median
      time to recurrence was 4.1 months. There were 28 deaths; overall, tumor grade
      showed a significant difference in time to tumor recurrence (p = 0.011) and time
      to death (p = 0.004). Time to death among stage 2 patients separated into those
      with high- and low-grade tumors reached statistical significance (p = 0.05), and
      notable but not statistically significant differences were identified in all
      stages. Based on tumor grade and survival curves, modifications to the current
      ENSAT staging system were made. CONCLUSION: Tumor grade plays a significant role
      in the outcome of patients with ACC. High-grade tumors are associated with
      shorter disease-free intervals and shorter overall survival. The proposed
      modification of the ENSAT staging system allows for incorporation of tumor grade
      when predicting overall survival.

PMID- 20694733
TI  - Fatal necrotizing fasciitis following two suicide attempts with petroleum oil
      injection.
AB  - PURPOSES: Necrotizing fasciitis is an aggressively progressing complication of
      the skin and soft tissue infections. It has dramatic course and often leads to
      patient's death. METHODS: In our research, we present the casuistic case
      concerning double suicide attempt with petroleum oil injection, complicated by
      the necrotizing fasciitis, patient was with deliberately withheld mental
      disorders. RESULTS: During the first suicide attempt, the oil substance was
      injected into the left cubital fossa and left toes areas, what lead to amputation
      of the upper left limb above the cubitial fossa and the left toes. Afterward,
      patient gradually recovered and survived. Two years later, another suicide
      attempt took place with the same substance: a 27-year-old man injected the
      petroleum oil into the right supraclavicular area. That affected a necrosis
      penetrating into the mediastinum and the patient died. CONCLUSIONS: To our
      knowledge, such case of the necrotizing fasciitis has not been previously
      reported. The mechanism of derivatives of oil influence on tissues is not
      investigated yet; therefore, treatment method is uncertain and sometimes
      ineffective.

PMID- 20694734
TI  - Sensitivity to change of the Neck Pain and Disability Scale.
AB  - The Neck Pain and Disability Scale (NPAD) is a 20-item instrument to measure neck
      pain and related disability. The aim of this study was to assess sensitivity to
      change of the NPAD. A total of 411 participants from 15 general practices in the
      middle of Germany completed a multidimensional questionnaire including the German
      version of the NPAD and self-reported demographic and clinical information.
      Sensitivity to change was analysed by linear regression analysis of the NPAD at
      follow-up and educational level, age class, depression, anxiety, and deficits in
      social support, respectively, and by Pearson's correlation analyses between mean
      change in NPAD at follow-up and mean change in prognostic markers. Those having
      more than basic education (regression coefficient -7.2, p < 0.001) and/or being
      in a younger age class (-2.9, p = 0.020) consistently reported significantly
      lower average NPAD scores at follow-up compared to those with basic education
      and/or a older age class. In contrast, those who were classified to be depressed
      (regression coefficient 2.1, p < 0.001), anxious (1.9, p < 0.001), or having
      deficits in social support (5.5, p = 0.004) reported significantly higher NPAD
      scores. Change in depression, anxiety, and social support scale between baseline
      and follow-up was significantly correlated with change in the NPAD score. Hence,
      these data are in the direction anticipated across all baseline factors
      investigated. In conclusion, the NPAD seems to be a sensitive measure for use in
      clinical practice and future studies of neck pain and related disability.

PMID- 20694735
TI  - Cervical spondylotic amyotrophy.
AB  - Cervical spondylotic amyotrophy is characterized with weakness and wasting of
      upper limb muscles without sensory or lower limb involvement. Two different
      mechanisms have been proposed in the pathophysiology of cervical spondylotic
      amyotrophy. One is selective damage to the ventral root or the anterior horn, and
      the other is vascular insufficiency to the anterior horn cell. Cervical
      spondylotic amyotrophy is classified according to the most predominantly affected
      muscle groups as either proximal-type (scapular, deltoid, and biceps) or distal
      type (triceps, forearm, and hand). Although cervical spondylotic amyotrophy
      always follows a self-limited course, it remains a great challenge for spine
      surgeons. Treatment of cervical spondylotic amyotrophy includes conservative and
      operative management. The methods of operative management for cervical
      spondylotic amyotrophy are still controversial. Anterior decompression and fusion
      or laminoplasty with or without foraminotomy is undertaken. Surgical outcomes of
      distal-type patients are inferior to those of proximal-type patients.

PMID- 20694736
TI  - Modeling the adsorptive selectivity of carbon nanotubes for effective separation
      of CO2/N2 mixtures.
AB  - Canonical Monte Carlo (CMC) simulations were carried out to investigate the
      behavior of CO(2) and N(2) mixtures upon adsorption on single walled carbon
      nanotubes (CNTs). In the simulation, all the particle-particle interactions
      between CO(2), N and C were modeled using Lennard-Jones (LJ) potential. To
      provide deep insight into the effect of pore width, temperature, pressure and
      bulk composition on the adsorption behavior of CO(2) /N(2) mixtures, five
      different CNTs [(6,6), (7,7), (8,8) (9,9) and (10,10) CNT] with diameters ranging
      from 0.807 to 1.35 nm, three temperatures (300 323 and 343 K), six pressures
      (0.15, 2, 4, 6, 8 and 10 MPa), and three bulk mole compositions of carbon dioxide
      (0.3 0.5 and 0.7) were tested. The results from all the simulation conditions
      investigated in this work show that CNTs preferentially adsorb carbon dioxide
      relative to nitrogen in a binary mixture. The results are consistent with the
      hypothesis that stronger interaction of one component with the nanotube surface
      results in a higher adsorption capacity compared to the other component. An
      optimized pore size of D = 8.07 nm corresponding to (6, 6) CNT, at T = 300 K and
      P = 0.15 MPa at a bulk mole composition of y(CO2) =0.3 was identified in which
      carbon nanotubes demonstrate the greatest selectivity for separation of carbon
      dioxide relative to nitrogen. In addition, it is worth pointing out that, under
      similar simulation conditions, CNTs exhibit higher selectivity compared to other
      carbon-based materials [carbon membrane polyimide (PI) and PI/multi-wall carbon
      nanotubes (MWCNTs)] for CO(2) adsorption. As a prototype, the selectivity of an
      equimolar mixture of CO(2) /N(2) for adsorption on (6, 6) CNTs at 300 K and 0.15
      MPa reaches 9.68, which is considerably larger than that reported in carbon
      membrane. Therefore, it can be concluded that carbon nanotubes can act as a
      capable adsorbent for adsorption/desorption of CO(2) in comparison with other
      carbon-based materials in the literature.

PMID- 20694737
TI  - Cellular communications in bone homeostasis and repair.
AB  - Cellular communication between the bone component cells osteoblasts, osteocytes
      and (pre-)osteoclasts is essential for bone remodeling which maintains bone
      integrity. As in the remodeling of other organs, cell death is a trigger for
      remodeling of bone. During the systematic process of bone remodeling, direct or
      indirect cell-cell communication is indispensable. Thus, osteoblasts induce
      migration and differentiation of preosteoclasts, which is followed by bone
      resorption (by mature multinuclear osteoclasts). After completion of bone
      resorption, apoptosis of mature osteoclasts and differentiation of osteoblasts
      are initiated. At this time, the osteoblasts do not support osteoclast
      differentiation but do support bone formation. Finally, osteoblasts differentiate
      to osteocytes in bone or to bone lining cells on bone surfaces. In this way, old
      bone areas are regenerated as new bone. In this review the role of cell-cell
      communication in bone remodeling is discussed.

PMID- 20694738
TI  - The epididymis-specific antimicrobial peptide beta-defensin 15 is required for
      sperm motility and male fertility in the rat (Rattus norvegicus).
AB  - Spermatozoa acquire forward motility and fertilizing capacity during their
      transit through the epididymis. The maturation process involves modifications of
      the sperm surface by different proteins that are secreted by a series of
      specialized regions in the epididymal epithelium. Here we show that the rat
      epididymis-specific beta-defensin 15 (Defb15) exhibits an androgen-dependent
      expression pattern, and it can bind to the acrosomal region of caput sperm.
      Coculture of caput spermatozoa with Defb15 antibody in vitro resulted in a
      significant decline in sperm motility. Moreover, the total and progressive
      motility of the spermatozoa dramatically decreased in rats when Defb15 was
      downregulated by lentivirus-mediated RNAi in vivo. Remarkably, knock down of
      Defb15 led to a reduction in fertility and embryonic development failure. In
      addition, the recombinant Defb15 showed antimicrobial activity in a dose
      dependent fashion. These results suggest that Defb15 plays a dual role in both
      sperm maturation and pathogen defense in rat epididymis.

PMID- 20694740
TI  - Thromboxane-prostanoid receptor expression and antagonism in dextran-sodium
      sulfate-induced colitis.
AB  - OBJECTIVE: In the current study of murine colitis, the potential roles of
      thromboxane and the thromboxane-prostanoid (TP) receptor were investigated, in as
      much as thromboxane signaling has been implicated in human inflammatory bowel
      disease. METHODS: Colitis was induced in C57BL/6 mice via ingestion of dextran
      sodium sulfate (DSS), with or without co-administration of the thromboxane
      synthase inhibitor ozagrel (25 mg/kg/day) or the TP receptor antagonist vapiprost
      (2.5 mg/kg/day). RESULTS: Immunohistochemistry of colonic tissue demonstrated a
      DSS-induced increase in TP receptor expression, but not of thromboxane synthase.
      Moreover, tissue levels of the metabolite thromboxane B(2) were unchanged by DSS.
      Vapiprost, but not ozagrel, partially attenuated histologic signs of inflammation
      induced by DSS, with vapiprost allowing a smaller increase in colon weight per
      unit length than ozagrel. Vapiprost also tended to attenuate DSS-induced
      alterations in intestinal transit. CONCLUSIONS: In summary, TP receptor
      antagonism was more effective than thromboxane synthase inhibition in alleviating
      DSS-induced colitis in mice.

PMID- 20694739
TI  - Triosephosphate isomerase: a highly evolved biocatalyst.
AB  - Triosephosphate isomerase (TIM) is a perfectly evolved enzyme which very fast
      interconverts dihydroxyacetone phosphate and D: -glyceraldehyde-3-phosphate. Its
      catalytic site is at the dimer interface, but the four catalytic residues, Asn11,
      Lys13, His95 and Glu167, are from the same subunit. Glu167 is the catalytic base.
      An important feature of the TIM active site is the concerted closure of loop-6
      and loop-7 on ligand binding, shielding the catalytic site from bulk solvent. The
      buried active site stabilises the enediolate intermediate. The catalytic residue
      Glu167 is at the beginning of loop-6. On closure of loop-6, the Glu167
      carboxylate moiety moves approximately 2 A to the substrate. The dynamic
      properties of the Glu167 side chain in the enzyme substrate complex are a key
      feature of the proton shuttling mechanism. Two proton shuttling mechanisms, the
      classical and the criss-cross mechanism, are responsible for the interconversion
      of the substrates of this enolising enzyme.

PMID- 20694741
TI  - Chicken feathers: a complex substrate for the co-production of alpha-amylase and
      proteases by B. licheniformis NH1.
AB  - This study is concerned with the co-production of alkaline proteases and
      thermostable alpha-amylase by some feather-degrading Bacillus strains: B.
      mojavensis A21, B. licheniformis NH1, B. subtilis A26, B. amyloliquefaciens An6
      and B. pumilus A1. All strains produced both enzymes, except B. pumilus A1, which
      did not exhibit amylolytic activity. The best enzyme co-production was obtained
      by the NH1 strain when chicken feathers were used as nitrogen and carbon sources
      in the fermentation medium. The higher co-production of both enzymes by B.
      licheniformis NH1 strain was achieved in the presence of 7.5 g/l chicken feathers
      and 1 g/l yeast extract. Strong catabolic repression on protease and alpha
      amylase production was observed with glucose. Addition of 0.5% glucose to the
      feather medium suppressed enzyme production by B. licheniformis NH1. The growth
      of B. licheniformis NH1 using chicken feathers as nitrogen and carbon sources
      resulted in its complete degradation after 24 h of incubation at 37 degrees C.
      However, maximum protease and amylase activities were attained after 30 h and 48
      h, respectively. Proteolytic activity profiles of NH1 enzymatic preparation grown
      on chicken feather or casein-based medium are different. As far as we know, this
      is the first contribution towards the co-production of alpha-amylase and
      proteases using keratinous waste. Strain NH1 shows potential use for
      biotechnological processes involving keratin hydrolysis and industrial alpha
      amylase and proteases co-production. Thus, the utilization of chicken feathers
      may result in a cost-effective process suitable for large-scale production.

PMID- 20694742
TI  - Deletion of the eIFiso4G subunit of the Arabidopsis eIFiso4F translation
      initiation complex impairs health and viability.
AB  - Arabidopsis thaliana knockout lines for the plant-specific eukaryotic translation
      initiation factors eIFiso4G1 (i4g1) and eIFiso4G2 (i4g2) genes have been
      obtained. To address the potential for functional redundancy of these genes,
      homozygous double mutant lines were generated by crossing individual knockout
      lines. Both single and double mutant plants were analyzed for changes in gross
      morphology, development, and responses to selected environmental stressors.
      Single gene knockouts appear to have minimal effect on morphology, germination
      rate, growth rate, flowering time, or fertility. However, double mutant i4g1/i4g2
      knockout plants show reduced germination rates, slow growth rates, moderate
      chlorosis, impaired fertility and reduced long term seed viability. Double mutant
      plants also exhibit altered responses to dehydration, salinity, and heat stress.
      The i4g2 and i4g1/i4g2 double mutant has reduced amounts of chlorophyll a and b
      suggesting a role in the expression of chloroplast proteins. General protein
      synthesis did not appear to be affected as the levels of gross protein expression
      did not appear to change in the mutants. The lack of a phenotype for either of
      the single mutants suggests there is considerable functional overlap. However,
      the strong phenotypes observed for the double mutant indicates that the
      individual gene products may have specialized roles in the expression of proteins
      involved in plant growth and development.

PMID- 20694743
TI  - Drcd-1 related: a positively selected spermatogenesis retrogene in Drosophila.
AB  - Gene duplication is a major force driving genome evolution, and examples of this
      mode of evolution and of the functions of duplicated genes are needed to reveal
      general patterns. Here, our study focuses on a particular retrogene (i.e.,
      CG9573) that originated about 5-13 million years ago that we have named Drcd-1
      related. It originated in Drosophila through retroposition of the parental gene
      Required for cell differentiation 1 of Drosophila (Drcd-1; CG14213), which is a
      known transcription cofactor. Drcd-1r is only present in D. melanogaster, D.
      simulans, D. sechellia, and D. mauritiana. Drcd-1r is an X to autosome
      retroposition event. Many retrogenes are X to autosome copies and it has been
      shown that positive selection underlies this bias. We sought to understand Drcd
      1r mode of evolution and function to contribute to the understanding of the
      selective pressures acting on X to autosome retrogenes. Drcd-1r overlaps with
      another gene, it is within the 3' UTR of the gene CG13102 and is encoded in the
      opposite orientation. We have studied the characteristics of the transcripts and
      quantified expression of CG13102 and Drcd-1r in wild-type flies. We found that
      Drcd-1r is transcribed specifically in testes. We also studied the molecular
      evolution of Drcd-1r and Drcd-1 and found that the parental gene has evolved
      under very strong purifying selection but the retrogene has evolved very rapidly
      (Ka/Ks ~1) under both positive and purifying selection, as revealed using
      divergence and polymorphism data. These results indicate that Drcd-1r has a novel
      function in the Drosophila testes. To further explore Drcd-1r function we used a
      strain containing a P element inserted in the region where CG13102 and Drcd-1r
      are located that shows recessive male sterility. Analysis of this strain reveals
      the difficulties that can be encountered in studying the functions of genes with
      overlapping transcripts. Avenues for studying of the function of this gene are
      proposed.

PMID- 20694744
TI  - The inhibition of autophagy potentiates anti-angiogenic effects of sulforaphane
      by inducing apoptosis.
AB  - BACKGROUND: Sulforaphane (SUL), a kind of isothiocyanate, has recently been
      focused due to its strong pro-apoptotic effect on cancer cells as well as tumor
      vascular endothelial cells (ECs). And recently, we demonstrated the induction of
      autophagy by colon cancer cells as a protective mechanism against SUL. In the
      present study, we aimed to investigate the possible role of autophagy induction
      by ECs as a defense mechanism against SUL. METHODS: Human umbilical vein
      endothelial cells (HUVECs) were used as the in vitro model of angiogenic ECs. The
      induction of autophagy was evaluated by the detection of acidic vesicular
      organelles (AVOs) by flow-cytometry, after the staining with acridine orange, as
      well as the detection of light chain 3(LC3) by Western blot. Finally, the
      functional implication of autophagy inhibition and SUL treatment in ECs was
      investigated by their ability to form vascular-like structures on Matrigel.
      RESULTS: Treatment of HUVECs with relatively low concentrations of SUL for 16 h
      resulted in the evident formation of AVOs and the recruitment of LC3 to
      autophagosomes, the pathognomonic features of autophagy. Co-treatment of cells
      with the specific autophagy inhibitor (3-methyladenine) potentiated the
      proapoptotic effect of SUL. And inhibition of autophagy potentiated the
      inhibitory effect of SUL on the ability of ECs to form capillary-like structures.
      CONCLUSION: Similar to cancer cells, ECs induced autophagy in response to the pro
      apoptotic agent, SUL, and the inhibition of autophagy potentiated the pro
      apoptotic effect. These findings open premises for the use of autophagy
      inhibitors in combination with anti-angiogenic agents.

PMID- 20694745
TI  - Dead-box or black-box: is DDX1 a potential biomarker in breast cancer?

PMID- 20694746
TI  - A comparison of the heart and muscle total lipid and fatty acid profiles of nine
      large shark species from the east coast of South Africa.
AB  - We have assessed the fatty acid profiles of the hearts and different muscle
      tissues from nine large shark species (Carcharhinus limbatus (blacktip),
      Carcharhinus obscurus (dusky), Carcharhinus brevipinna (spinner), Carcharhinus
      leucas (Zambezi/bull), Galeocerdo cuvier (tiger), Sphyrna lewini (scalloped
      hammerhead), Sphyrna zygaena (smooth hammerhead), Carcharodon carcharias (great
      white) and Carcharias taurus (raggedtooth/grey nurse/sand tiger)) found off the
      east coast of South Africa. While there was generally little variation between
      the species, all species showed profiles rich in both n6 and n3 polyunsaturated
      fatty acids compared to terrestrial commercial meats that have low n3. Thus,
      utilizing skeletal muscle tissues from sharks caught as part of the bycatch when
      fishing for teleosts would avoid unnecessary wastage of a potentially valuable
      resource, with all the possible health benefits of high quality protein combined
      with balanced polyunsaturates, although contamination with high levels of
      metabolic wastes, such as urea, may be a negative consideration.

PMID- 20694747
TI  - Multiwalled carbon nanotubes activate NF-kappaB and AP-1 signaling pathways to
      induce apoptosis in rat lung epithelial cells.
AB  - Our previous report on multiwall carbon nanotubes (MWCNT) has demonstrated the
      generation of reactive radicals and depletion of intracellular antioxidants which
      in turn cause cell death through activation of caspases. The molecular mechanism
      of cellular death due to MWCNT is not clear yet. In this study, we investigated
      the signaling pathways implicated in MWCNT-induced apoptosis in rat lung
      epithelial cells. First, we assessed the DNA damage in response to MWCNT
      treatment and showed the significant DNA damage as compared to control. The
      collapse of the mitochondrial membrane integrity, release of cytochrome c into
      the cytosol, reduction in cellular ATP content, increased levels of mitochondrial
      apoptogenic factor and activation and nuclear translocation of NF-kappaB were
      observed in MWCNT treated cells. In addition, a time-dependent induction of
      phosphorylated IkappaBalpha and its degradation were detected in cells exposed to
      MWCNT. Furthermore, MWCNT activated several death related proteins including
      apoptosis inducing factor, p53, p21 and bax. Together, our results suggest that
      signaling pathways such as NF-kappaB and AP-1 are activated upon MWCNT treatment
      for cellular cytotoxicity.

PMID- 20694748
TI  - Peak systolic longitudinal strain of the lateral left ventricular wall improves
      after septal ablation for symptomatic hypertrophic obstructive cardiomyopathy: a
      follow-up study using speckle tracking echocardiography.
AB  - Speckle tracking echocardiography (STE) or two-dimensional (2D) strain imaging is
      a novel ultrasound method to assess myocardial deformation. Peak systolic
      longitudinal strain (PSLS) of the basal septum (IVS) and the opposite lateral
      (LVFW) wall were measured in addition to standard echocardiography in 88
      consecutive patients (pts) with obstructive hypertrophic cardiomyopathy (HOCM)
      who underwent a septal ablation procedure (PTSMA) and who were re-evaluated 12 +/
      12 after months. At baseline, PSLS was substantially reduced both in basal
      regions. While PSLS remained unchanged in the basal IVS, i.e. the target region
      for PTSMA (baseline: -5.3 +/- 4.1%; follow-up: -6.0 +/- 4.3%; P=0.06), it
      improved in the opposite LVFW (from -9.4 +/- 4.7 to -12.4 +/- 4.8%; P<0.0001).
      Wall thickness decreased in both regions (Septum: from 20 +/- 4 to 17 +/- 4 mm;
      P<0.0001; LV free wall: from 13 +/- 2 to 12 +/- 2 mm; P=0.001). PSLS correlated
      significantly with wall thickness, both at baseline and at follow-up. NYHA
      functional class (from 2.9 +/- 0.4 to 1.6 +/- 0.6; P<0.0001) and objective
      exercise capacity (from 96 +/- 42 to 114 +/- 42 W; P=0.001) improved together
      with the reduction of outflow obstruction (LVOTO: from 62 +/- 30 to 11 +/- 19 mm
      Hg at rest, from 121 +/- 26 to 43 +/- 40 mm Hg with provocation; P<0.0001).
      During the 12 months of observation, no patient had a severe adverse event.
      Regional myocardial deformation can be assessed quantitatively by STE. Reduction
      of LV afterload by elimination of the outflow gradient following a successful
      PTSMA with low doses of alcohol results in improvement of systolic lateral
      longitudinal function.

PMID- 20694749
TI  - Comprehensive BRCA1 and BRCA2 mutation analyses and review of French Canadian
      families with at least three cases of breast cancer.
AB  - Few studies have reported on the comprehensive BRCA1/2 mutation analyses of
      hereditary breast cancer (HBC) families of French Canadian descent. Here we
      report the investigation of 82 families with at least 3 cases of breast cancer
      evaluated for mutations by DNA sequencing and/or multiplex ligation-dependent
      probe amplification (MLPA) assay. DNA sequencing identified pathogenic mutations
      in 37 (45.1%) families, of which 70.2% were one of three recurring mutations
      (BRCA1:R1443X, BRCA2:8765delAG, and BRCA2:E1953X) frequently reported in this
      founder population; and variants of uncertain clinical significance in 7 (8.5%)
      families of which two harbored BRCA2:E3002K. MLPA analysis of the 38 DNA sequence
      negative families did not reveal any large rearrangements in BRCA1/2. A
      phenotypic characterization of the cancer families based on pathogenic mutation
      status revealed that there were significantly fewer very young age at diagnosis
      breast cancer cases (<36 years) in mutation-negative families (5.9%, 9 of 153)
      than in BRCA1 (22.8%, 13 of 57; P = 0.0003) or BRCA2 (22.9%, 27 of 118; P < 1*
      10E5) mutation-positive families. There were significantly more mutation-positive
      families (29 of 36, 80.6%) with a very young age of onset of breast cancer case
      than those that did not (8 of 39, 20.5%) (P < 10E6). The comprehensive mutation
      analysis of BRCA1/2 suggests that genomic rearrangements are unlikely to account
      for sequence-negative HBC families and affirms that the presence of a very young
      age of diagnosis of breast cancer is strongly predictive of mutation carrier
      status of French Canadian HBC families.

PMID- 20694750
TI  - A review of 100 consecutive sutureless child and adult circumcisions.
AB  - BACKGROUND: Circumcision is one of the world's most common operations. Series
      describing a new technique involving the use of fibrin-based glue have become
      more apparent in the literature. Here we outline the first 100 such cases for 62
      children and 38 adults in our practice describing complications and learning
      curve. METHODS: We reviewed all cases noting age, indication, cosmetic appearance
      and any potential complications. Reviews were carried out 2-6 weeks
      postoperatively. RESULTS: Phimosis accounted for 42% of cases; 58% were for
      religious reasons. Ages ranged from 6 months to 72 years, with 99% satisfied with
      the cosmetic immediate postoperative appearance. Three had minor delayed post-op
      bleeding, none necessitating a return to theatre. One had a reaction to the glue
      requiring antihistamines for a week. Two postoperative cases of balanitis were
      reported. CONCLUSION: Sutureless circumcision is a practical alternative to the
      standard method. This series supports a role for sutureless circumcisions in
      adults.

PMID- 20694751
TI  - Prevalence and clinical significance of 15 autoantibodies in patients with new
      onset systemic lupus erythematosus.
AB  - INTRODUCTION: It is necessary to assay multiple autoantibodies simultaneously in
      the same group of new-onset systemic lupus erythematosus (SLE) patient. AIM: To
      determine the prevalence and clinical significance of 15 autoantibodies in
      patients with new-onset SLE. METHODS: Twenty new-onset patients with SLE and 32
      healthy individuals were enrolled in the present study. Serum levels of 15
      autoantibodies were detected by enzyme linked immunosorbent assay. The clinical
      parameters of the patients were also recorded. RESULTS: The positive rate of anti
      ssDNA was the highest (85%). The positive rates of anti-dsDNA, anti-ssDNA, AHA,
      anti-SSA, anti-SSB, anti-Sm, anti-U1RNP, AnuA, and rRNP were significantly higher
      in SLE patients than in nomal controls. In terms of clinical manifestation, there
      were significant associations of rRNP with photaesthesia and of AHA with
      nephritis. CONCLUSION: Clusters of autoantibodies were identified and
      associations of antibodies with symptoms were found in new-onset patients with
      SLE.

PMID- 20694752
TI  - [Radiological procedures in the traumatised wrist].
AB  - Injuries of the wrist are difficult to diagnose because of the complex and narrow
      anatomic structures. On the basis of precise clinical examination, X-rays, CT and
      MRI are valuable additional tools that can be used. In the case of bone injury,
      spiral computer tomography with multiplanar reformatting is currently the method
      of choice. MRI is indicated for the identification of soft tissue or ligamentous
      injury and avital fragments or necrosis. Other diagnostic tools for the wrist are
      currently of minor importance. Technical and methodological innovations allow
      ever better visualisation and classification of lesions, as well as their extent,
      thus enabling more targeted therapy. However, prerequisites of effective use
      include differential assessment and precise knowledge of the procedures.

PMID- 20694756
TI  - Abstracts of the Annual Symposium of the Society for the Study of Inborn Errors
      of Metabolism. Istanbul, Turkey. August 31-September 3, 2010.

PMID- 20694755
TI  - Clomipramine treatment and repeated restraint stress alter parameters of
      oxidative stress in brain regions of male rats.
AB  - This study aimed to compare the effects of repeated restraint stress alone and
      the combination with clomipramine treatment on parameters of oxidative stress in
      cerebral cortex, striatum and hippocampus of male rats. Animals were divided into
      control and repeated restraint stress, and subdivided into treated or not with
      clomipramine. After 40 days of stress and 27 days of clomipramine treatment with
      30 mg/kg, the repeated restraint stress alone reduced levels of Na(+), K(+)
      ATPase in all tissues studied. The combination of repeated restraint stress and
      clomipramine increased the lipid peroxidation, free radicals and CAT activity as
      well as decreased levels of NP-SH in the tissues studied. However, Na(+), K(+)
      ATPase level decreased in striatum and cerebral cortex and the SOD activity
      increased in hippocampus and striatum. Results indicated that clomipramine may
      have deleterious effects on the central nervous system especially when associated
      with repeated restraint stress and chronically administered in non therapeutic
      levels.

PMID- 20694757
TI  - [Communication and autonomy - key topics in palliative medicine].

PMID- 20694758
TI  - [Vertigo as a symptom of psychosocial pain].
AB  - Vertigo in a patient with end stage lung cancer challenges the caring team. No
      relief can be achieved by various treatment attempts. In a retrospective analysis
      it turns out that the physical symptom of vertigo makes up for psychosocial pain.
      Causes for this reaction can be found in the patient's history and deal with
      solitude and loss in a wider sense. Finding out what means quality of life to an
      individual patient leads to general ideas about human needs. Considerations about
      the best place to stay for a dying person need to be merged with the options a
      medical system offers.

PMID- 20694759
TI  - [Communication with palliative care patients: truth and hope--a contradiction?].
AB  - Especially in western countries an open communication with cancer patients has
      gained increasing importance in the last years. Balancing between truth and hope
      in view of bad prognosis presents a special challenge. Oncologists have the
      responsibility and duty of truthful disclosure. On the other hand they have to
      accept the patients handling with given information and to respect that sometimes
      patients do not want to know the whole truth. In this paper the difficulties to
      prevent hope and the importance of an individualized and empathic care will be
      discussed on the basis of a case report.

PMID- 20694760
TI  - Resilience, childhood disability and the Internet--case report.
AB  - We describe a family with a severely disabled child who demonstrates many of the
      characteristics of resilient families: strong relationships, good communication,
      and profound love of the disabled child. But this family has a characteristic
      that is infrequently described in the literature yet common in practice: the
      mother initiated many medical decisions based on knowledge gathered on the
      Internet. Parental education on the Internet can now allow families to gain a
      sense of mastery over their child's disease.

PMID- 20694761
TI  - [Percutaneous endoscopic gastrostomy-tube for a patient with glioblastoma to
      enable his admission into a nursing home].
AB  - The medical care for people in the end-stage of their carcinoma-disease demands
      extensive medical and nursing resources. If the admission to a hospice is not
      possible because of financial and personal reasons, or the medical care at home
      cannot be fulfilled personnel, a medical care in a nursing home would be possible
      for some patients on condition that a stable general condition and the support of
      mobile palliative teams are given. Besides a practicable pain therapy and the
      control of symptoms the hydration and ingestion are the criteria for the approval
      to a possible admission to a nursing home. If the ingestion is only limited
      possible respectively impossible and no advance directive respectively nor
      provision full power can be submitted, the admission is often denied, because
      mainly the people occupying a nursing profession are afraid to be situated in an
      ethic or lawful dispute situation, despite comprehensive information.

PMID- 20694762
TI  - [Ethical discussion of palliative sedation].
AB  - This article discusses ethical implications of palliative sedation at the end of
      life. Terminal or palliative sedation, like other denominations are discussed in
      literature, which invite to a profound discussion. From an ethical point of view,
      terminal or palliative sedation seems to be a way out when in intolerable
      suffering or situations without prospects, the demand for euthanasia arises. The
      possibility to use palliative sedation for effective control of otherwise
      refractory suffering provokes the question if it even can be used with the
      intention to hasten death. This has led to ethical concerns on the use and limits
      of sedation. Therefore it seems to be necessary to elaborate clear guidelines in
      handling sedation in end-of-life care to prevent misuse. The contribution of
      ethical considerations can clarify the position and use of palliative sedation.

PMID- 20694763
TI  - [Palliative sedation therapy for severe dyspnoea].
AB  - In this case study we report on a patient with advanced myxofibrosarcoma and lung
      metastases, suffering from severe dyspnoea. Symptoms were not manageable by means
      of standard palliative care, which made palliative sedation therapy necessary in
      order to alleviate dyspnoea. On the basis of this case study, indications, drugs,
      therapy monitoring and ethical aspects of palliative sedation therapy are
      discussed.

PMID- 20694764
TI  - [Limits of curation and palliation].
AB  - Informed consent is the condition for treating a patient, in curative and
      palliative settings. If, due to the medical situation, a valid consent cannot be
      acquired a substituted judgement based on information about the patients
      preferences will be applied. Accordingly the mobile palliative team of Caritas
      Socialis requires that patients are informed about their disease condition and
      agree to palliative measures. The team asks for clear communication about end of
      life situations, death and dying, which is sometimes difficult for relatives and
      patients. Sometimes defense mechanisms appear to deny the true situation in order
      to cope with the disease. The case report shows an example of a particular
      problematic challenge to combine palliative ideas with impossible curative hopes.
      An open discussion tries to clarify positions and seeks for future solutions.

PMID- 20694765
TI  - Sleep apnea is common in patients with coronary artery disease.
AB  - Sleep-disordered breathing (SDB) has a prognostic impact in patients with cardiac
      diseases. We included 257 patients with preserved left ventricular function and
      angiographically proven coronary artery disease (CAD). All patients underwent
      cardiorespiratory polygraphy. In 251 patients high-sensitive C-reactive protein
      and fibrinogen were measured. SDB was documented in 188 patients (apnea-hypopnea
      index [AHI] 16.4+/- 1.9/h): 58 patients presented central sleep apnea (CSA) and
      130 patients obstructive sleep apnea (OSA). All patients (73%) with SDB had
      higher blood fibrinogen levels than those without SDB (p = 0.01). We found 197
      patients with CRP-values below the cut-off of 0.5 mg/dl (group 1) and 54 patients
      with no active infection but CRP>0.5 mg/dl (group 2). Severity of SDB was
      significantly higher in group 2 (p = 0.01). SDB has a high prevalence in CAD
      patients and seems to be associated with chronic inflammation, which may be
      linked to CAD progression and/or acute coronary events.

PMID- 20694766
TI  - The extent of inaccurate aneroid sphygmomanometers in a hospital setting.
AB  - All 832 hospital hand-held aneroid sphygmomanometers without exception were
      examined for their accuracy within a +/- 3 mmHg margin by comparing them to a
      certified mercury device. Of these, 59.9% were inaccurate, with the majority
      giving lower readings than noted on the mercury scale. The findings are
      unsatisfactory and correspond to earlier reports whose study designs and
      interpretations of permissible limits varied widely. The instruments daily wear
      and tear is compounded by damage incurred by dropping and/or jolting, which could
      render the device inaccurate. Although it is generally recommended that aneroid
      manometers be inspected every six months, this seems not to be adequate.

PMID- 20694767
TI  - [Effects of acute altitude exposure: which altitude can be tolerated?].
AB  - Exposures to natural and simulated altitudes are combined with a reduction of the
      available oxygen (hypoxia) and may provoke health problems or even emergencies.
      Although millions of people are living at high altitudes, are regularly or
      occasionally performing mountain sport activities, are transported by airplanes,
      and are increasingly frequently exposed to hypoxia at their workplace, e.g. with
      fire control systems, there is no consensus about the level of hypoxia which is
      well tolerated by most of human beings. Thus, the present mini review tries to
      define such a level. This review indicates that although humans show adaptive
      responses even to altitudes below 2000 m or corresponding normobaric hypoxia
      (FiO2: >16%) most of these subjects without severe pre-existing diseases well
      tolerate altitudes up to 3000 m (FiO2: 14.5%). If at all, symptoms of acute
      mountain sickness may develop in some persons after a minimum exposure time of
      about 6 hours. This also applies to children, elderly persons and pregnant women.
      Physical activity and unusual environmental conditions may increase the risk to
      get sick. Also patients with not severe cardiovascular, respiratory or metabolic
      diseases well tolerate such levels of altitude. However, individual differences
      in responses to hypoxia have to be considered and can at least partly be tested
      by simple hypoxia challenge tests. For safety reasons altitudes up to 2700 m or
      normobaric hypoxia up to FiO2 values of 15% are proposed to be well tolerated by
      most humans who are not severely diseased.

PMID- 20694768
TI  - Infrarenal aortic coarctation.
AB  - Hypoplastic infrarenal aorta or infrarenal aortic coarctation is an uncommon
      vascular pathology characterized with diffuse stenosis in the infrarenal
      abdominal aorta. It is a variant of atherosclerotic occlusive diseases. The exact
      incidence and etiology are not known. Presenting symptoms are versatile and
      incidentally most of the patients have severe hypertension with an unidentified
      mechanism. Here, we report a 49-year-old male patient diagnosed with abdominal
      aortic coarctation together with the review of the literature. He underwent
      successful revasvcularization of the lower extremities.

PMID- 20694770
TI  - Herb-drug interaction: an emerging issue of integrative medicine.

PMID- 20694771
TI  - Recent clinical trials of acupuncture in the West: responses from the
      practitioners.
AB  - In the West, hundreds of randomized controlled trials (RCTs) have been performed
      testing acupuncture. They include two types: those that compare acupuncture to
      other therapies, usual care or no treatment (pragmatic trials), and those that
      have placebo controls (efficacy trials). Acupuncture has generally performed well
      against other therapies or no treatment, but until recently, the evidence from
      placebo controlled trials has been considered equivocal or contradictory. A
      recent series of large RCTs, mostly performed in Germany and also in the US have
      included both pragmatic and placebo comparisons. The evidence poises a conundrum
      for the profession of acupuncture. This essay first describes the two types of
      RCTs used to examine acupuncture and examine the results of two recent large RCTs
      for chronic low back pain as representative examples of recent large studies. The
      essay then presents the most common Euro-American acupuncture professions'
      interpretation of these results. Western responses have included: (1)
      methodological weaknesses; (2) inappropriateness of placebo controls; (3)
      questions as to whether acupuncture placebo controls are "inert"; (4) rejection
      of evidence-based medicine epistemology; (5) discrepancy between acupuncture
      performed in RCTs with real world acupuncture; (6) enhanced placebo effects of
      acupuncture; and (7) needs to re-evaluate acupuncture theory. The authors do not
      necessarily agree with all of these responses; they are presented in an attempt
      to foster critical discussion. The paper also looks at recent neuroimaging
      experiments on acupuncture that may point to some worthwhile new avenues of
      investigation. Finally, the Euro-American health care policy consequences of
      these recent RCTs are discussed.

PMID- 20694772
TI  - Definition and classification of acute kidney injury: contributions and problems
      in the clinical practice.

PMID- 20694773
TI  - Experiences on the integrative medical diagnosis and treatment of acute kidney
      injury.

PMID- 20694774
TI  - Preliminary experience of integrative medicine in acute kidney injury.

PMID- 20694775
TI  - Effect of traditional and integrative regimens on quality of life and early renal
      impairment in elderly patients with isolated systolic hypertension.
AB  - OBJECTIVE: To observe the effect of Chinese medical regimen and integrative
      medical regimen on quality of life and early renal impairment in elderly patients
      with isolated systolic hypertension (EISH). METHODS: A multi-center, randomized,
      double-blinded controlled trail was adopted. A total of 270 cases of EISH were
      randomly divided into 3 groups: Chinese medicine group (CM), combination group
      and Western medicine group (WM). The course of treatment was 4 weeks. The
      clinical blood pressure, integral of quality of life (SF-36 scale), immunoglubin
      G (IgG), microalbumin (mALB), beta(2)-microglobulin (beta(2)-MG), transferrin
      (TRF) and N-acetyl-beta'-D-glucosa-minidase (NAG) in urine were determined before
      and after the treatment. RESULTS: After treatment, systolic blood pressure
      depressed significantly in each group (P<0.05), and the combination group was
      superior to CM or WM group in depressing SBP (P<0.05); in each group, integral of
      quality of life improved in different degree, and combination group was superior
      to WM group in all 8 dimensions (P<0.05). The level of mALB and beta(2)-MG in
      urine decreased in all groups (P<0.05), and the combination group was superior to
      CM group or WM group in decreasing mALB (P<0.05). CONCLUSIONS: Chinese medical
      regimen has affirmative effect in treating EISH patients, and could lower the
      systolic blood pressure, improve quality of life and early renal impairment of
      the patients, and integrative medical regimen has superiority on account of
      cooperation, and deserves further study.

PMID- 20694776
TI  - Treatment of inflammatory bowel disease with Chinese drugs administered by both
      oral intake and retention enema.
AB  - OBJECTIVE: To study the clinical effect of Chinese drugs administered by both
      oral intake and retention enema on inflammatory bowel diseases (IBD). METHODS:
      Adopting a randomized controlled design, 78 patients were assigned to three
      groups: 26 patients in group A treated with Chinese drugs given by both oral
      intake and retention enema, 27 in group B with Chinese drugs given by retention
      enema only, and 25 in group C with given Western medicine. The changes before and
      after a 30-day treatment of the patients' symptoms (including diarrhea, abdominal
      pain, mucous or pus-bloody stool), colonoscopic examination scores and
      histopathology of the colonic membrane were observed. RESULTS: Group A showed the
      best outcomes in all the aspects of clinical comprehensive effectiveness.
      Improvements in the main symptoms, colonoscopic scores and histopathology of the
      colonic membrane were significantly different from those in groups B and C,
      respectively (P<0.05). Meanwhile comparisons between groups B and C showed
      insignificant differences (P>0.05); group B was better in ameliorating tenesmus
      (P<0.05). CONCLUSION: Through the use of Chinese drugs administered by both oral
      intake and retention enema to treat IBD, which combined external-internal
      therapies for both overall regulation and local management, it was confirmed that
      the Chinese medicine could embody the therapeutic principle of attending to both
      disease-diagnosis and syndrome-differentiation.

PMID- 20694777
TI  - Effect of electroacupuncture preconditioning on serum S100beta and NSE in
      patients undergoing craniocerebral tumor resection.
AB  - OBJECTIVE: To investigate the effect of electroacupuncture preconditioning on the
      serum level of S100 calcium-binding protein beta (S100beta) and neuron-specific
      enolase (NSE) in patients undergoing craniocerebral tumor operation. METHODS: A
      total of 32 patients, who would go through craniocerebral tumor resection under
      general anesthesia, were randomly assigned to two groups, 16 in each group.
      Patients in the electroacupuncture (EA) group received electroacupuncture on
      Fengfu acupoint (Du16) and Fengchi acupoint (GB20) for 30 min, 2 h before
      operation. The stimulus is 1-4 mA with a density wave frequency of 2/15 Hz.
      Patients in the control group received no pretreatment. Anesthesia was maintained
      with remifentanil at the dose of 4-8 mg/kg per hour, pumped intravenous drip of
      vecuronium at 1.0-2.0 microg/kg each hour, and discontinuous intravenous dripped
      with vecuronium bromide at 0.5-1 mg. The serum levels of S100beta and NSE were
      measured with ELISA before operation, before skin incision, after tumor removal,
      at the end of operation, and at 24 h after operation. RESULTS: The serum level of
      S100beta and NSE did not change before skin incision. The serum level of NSE
      increased significantly and the level of S100beta increased insignificantly after
      the tumor resection. The serum levels of S100beta and NSE in the EA group and the
      control group were 1.16+/-0.28 microg/L vs 1.47+/- 0.33 microg/L, 24.7+/-13.3
      microg/L vs 31.4+/-14.1 microg/L at the end of the operation, respectively.
      Twenty-four h after operation, the correspondence indices were 1.18+/-0.31
      microg/L vs 1.55+/-0.26 microg/L, and 25.5+/-12.4 microg/L vs 32.4+/- 11.7
      microg/L. The two indices at these two time points were significantly increased
      than those before operation, respectively (P<0.05). At the end of the operation
      and 24 h post-operation, the serum levels of S100beta and NSE in the EA group
      were significantly lower than those in the control group (P<0.05). CONCLUSION:
      Electroacupuncture Fengchi and Fengfu for 30 min before craniocerbral tumor
      operation could decrease the serum level of S100beta and NSE, thus may have
      potential protective effect on brain damage, which needs to be further studied.

PMID- 20694778
TI  - Transcutaneous electrical nerve stimulation on acupoints relieves labor pain: a
      non-randomized controlled study.
AB  - OBJECTIVE: To investigate the efficacy of transcutaneous electrical nerve
      stimulation (TENS) on four specific acupuncture points Hegu (LI4), Neiguan (PC6),
      Danshu (BL19) and Weishu (BL21) for reducing pain in labor. METHODS: A total of
      160 voluntary nulliparous women who were willing to receive TENS for analgesia
      were assigned to the treatment group after cervical dilation of more than 2 cm.
      Another 145 matched nullipara were recruited as the control group. Visual
      analogue scale (VAS) was used to assess the pain before and 0.5 h after the
      application of TENS. Then, VAS was assessed every one hour until delivery.
      Percentage of VAS score decreased by > 25% was the primary outcome, the delivery
      mode and neonatal outcome were measured as secondary outcomes. Adverse reactions
      were also recorded during TENS. RESULTS: The percentage of VAS score decreased by
      > 25% was 68.6% in the TENS treatment group. Maternal delivery mode and neonatal
      outcomes were not significantly different between the two groups. In addition,
      the incidence of postpartum hemorrhage in the TENS treatment group was less than
      the control group (P<0.05). There was no adverse reaction recorded with TENS on
      acupoints. CONCLUSION: As a novel and non-invasive approach, TENS on specific
      acupoints including Hegu (LI4), Neiguan (PC6), Danshu (BL19) and Weishu (BL21)
      was an effective method for analgesia in labor.

PMID- 20694779
TI  - Effects of Huanshuai Recipe Oral Liquid on restructuring glomerular
      microvasculature and expression of vascular endothelial growth factor in subtotal
      nephrectomized rats.
AB  - OBJECTIVES: To explore the effects and significance of Huanshuai Recipe Oral
      Liquid (, HSR), a formula with supplementing qi, nourishing blood and activating
      blood on restructuring glomerular microvasculature and expression of vascular
      endothelial growth factor (VEGF) in subtotal nephrectomized (SNX) rats. METHODS:
      A total of 76 male Wistar rats were randomly divided into four groups: 16 in the
      sham-operated group and fed with tap water 10 mL/kg per day; 20 in the model
      group were operated with 5/6 SNX and fed with tap water 10 mL/ kg per day; 20 SNX
      rats in the HSR group were treated with HSR 10 mL/kg per day; 20 SNX rats in the
      losartan group were treated with losartan 40 mg/kg per day. Serum creatinine
      (SCr) and urinary protein excretion (Upro) were examined at the 2nd, 4th, 8th,
      and 12th weeks of the treatment, and the remnant kidneys were harvested. Changes
      in histological microstructure were evaluated using light microscopy, and the
      expression of VEGF was detected by using ELISA. RESULTS: Upro, microvasculature
      injury and glomerulosclerosis were found to be alleviated in HSR and Losartan
      groups, respectively. The change of VEGF expression showed positive correlation
      with glomerular capillary area and peritubular capillary number (r=0.448,
      r=0.422, P<0.01), but negative correlation with that of SCr and Upro (r=-0.592,
      r=-0.481, P<0.01). CONCLUSIONS: HSR could regulate the VEGF expression, reduce
      the loss of microvasculature, which demonstrated similar renal protective effects
      to losartan in SNX rats. Examination of Chinese herbal medicine influence on VEGF
      signaling and restructuring renal microvasculature may elucidate the molecular
      mechanism of renal protection to a certain degree.

PMID- 20694780
TI  - Effect of Chinese herbal medicine for activating blood circulation and
      detoxifying on expression of inflammatory reaction and tissue damage related
      factors in experimental carotid artery thrombosis rats.
AB  - OBJECTIVE: To observe the pharmaceutical effect of Chinese drugs for activating
      blood circulation (Xiongshao Capsule, XSC, ) and for activating blood circulation
      and detoxification (Xiongshao Capsule and Huanglian Capsule, XSHLC, ) in terms of
      the indices of thrombosis, inflammatory reaction and tissue damage related
      factors in experimental carotid artery thrombosis rats. METHODS: Fifty Wistar
      rats were randomly divided into the sham operation group, the model group, the
      Simvastatin group (SG), the activating blood circulation (ABC) group, and the
      activating blood circulation and detoxifying (ABCD) group, with 10 rats in each
      group. Simvastatin (1.8 mg/kg), XSC (0.135 g/kg) and XSHLC (0.135 g/kg) were
      administered to Simvastatin, ABC and ABCD group by gastrogavage, and an equal
      volume of normal saline was given to the sham operation group and the model
      group. After 2 weeks of successive medication, the rats in the model and all drug
      therapy groups were made into experimental carotid artery thrombosis model. The
      serum levels of matrix metalloproteinases (MMP-9), tissue inhibitors to
      metalloproteinase (TIMP-1), granule membrane protein-140 (GMP-140), tissue-type
      plasminogen activator (t-PA), high-sensitivity C-reactive protein (hs-CRP) and
      interleukin-6 (IL-6) were detected with enzyme-linked immunoassay 24 h later.
      RESULTS: Compared with the model group, the levels of serum GMP-140, hs-CRP, IL-6
      and MMP-9 were significantly decreased, and the level of t-PA was significantly
      increased in the ABC and ABCD group ( P<0.05), while the level of serum hs-CRP in
      ABCD group decreased significantly compared with that in the ABC group (P<0.05).
      CONCLUSIONS: Chinese drugs both for activating blood circulation and for
      activating blood circulation and detoxifying have good effects on regulating
      indices of thrombosis, inflammatory reaction and tissue damage in experimental
      carotid artery thrombosis rats. The effect of activating blood circulation and
      detoxifying drugs on regulating the level of serum hs-CRP is superior to that of
      activating blood circulation drug alone.

PMID- 20694781
TI  - Effect of Kangshuai Yizhi Formula I on learning and memory dysfunction induced by
      scopolamine in mice.
AB  - OBJECTIVE: To evaluate the improvement of Kangshuai Yizhi Formula I ( I, KYF I)
      on: the learning and memory dysfunction in mice, and on the mechanism of the
      hippocampal cholinergic system and the nervous system of monoamine which are
      closely related to learning and memory function. METHODS: Mice: in the low-,
      middle-, and high-dose KYF I groups were given low-, middle-, and high-dose KYF,
      respectively, by gastrogavage for 35 successive days. Animals in the control
      group and the model group were treated with distilled water. The acute learning
      and memory dysfunction model was established by injection of scopolamine from day
      31, and Morris water maze was used to assess the behavior performance of
      scopolamine-induced model mice for five days. The activities of
      acetylcholinesterase (AChE), choline acetyl transferase (ChaT) and the content of
      monoamine neurotransmitters in hippocampus were measured. The activity of
      monoamine oxidase (MAO) in hippocampus and serum was also detected. RESULTS: (1)
      Compared with the control group, the: mean escape latency was shortened, and the
      frequency across the platform and the staying time at the platform area on the
      5th day were decreased in the model group by Morris water maze test. The
      activities of AChE and MAO were increased, and the ChaT activity and monoamine
      neurotransmitter content were decreased as well. (2) The escape latency for 4
      days in the low-, middle-, and high-dose KYF I groups was significantly shortened
      than that in the model group, with the shortest latency in the high-dose KYF I
      group (P<0.05, P<0.01). The frequency across the platform was significantly
      increased and the staying time at the platform was significantly prolonged in the
      middle- and high-dose KYF I groups (P<0.05, P<0.01). (3) As compared with the
      model group, the activity of ChaT and the content of monoamine neurotransmitters
      in the hippocampus were significantly increased, and the activities of AchE and
      MAO were significantly decreased in the hippocampus in the high-dose KYF I group
      (P<0.01). CONCLUSIONS: High-dose KYF I can significantly improve the learning and
      memory dysfunction: induced by scopolamine in mice. Its mechanism may be related
      to improving the central cholinergic system and regulating the hippocampal
      monoamine neurotransmitters.

PMID- 20694782
TI  - Effects of Erlong Zuoci pill and its disassembled prescriptions on gentamicin
      induced ototoxicity model in vitro.
AB  - OBJECTIVE: To study the effects of Erlong Zuoci Pill (, ELZCP) and its
      disassembled: prescriptions on gentamicin (GM)-induced ototoxicity model in
      vitro. METHODS: After the spiral organ of cochleae: of newborn mice (postnatal
      days: 2-3) cultured for 24 h, GM alone or combined with water extracting-alcohol
      precipitating solution of ELZCP or with its disassembled prescriptions was added.
      Hair cells were observed under a fluorescence microscope after TRITC-phalloidin
      staining, and the cochlear hair cell loss rate was calculated by counting the
      whole cochlear hair cells and analyzed by whole cochlear hair cells analyzing
      software. RESULTS: GM induced cochlear outer hair cells (OHCs) and inner hair
      cells (IHCs) injuries in a dose-dependent manner, and they were significantly
      different as compared with those in the normal control group (P<0.05, P<0.01).
      ELZCP at the concentration of 0.003-3 mg/mL could decrease the hair cells loss
      induced by the 0.3 mmol/L GM (P<0.05, P<0.01), the effects was in a dose
      dependent manner, and the concentration of 0.3 mg/mL showed the optimal
      protective effect. For the ELZCP disassembled prescriptions, Liuwei-Dihuang could
      decrease OHC loss rate than that in the 0.3 mmol/L GM model group (P<0.05), but
      the OHC loss rate was still higher than that in the ELZCP group (P<0.01), which
      indicated that the protective effect of hair cells by Liuwei-Dihuang was not
      better than that of ELZCP. Poria decreased OHC loss rate from 72.1 % +/-3.7 % to
      58.8 %+/- 8.2 % (P<0.05). CONCLUSIONS: ELZCP could play a role in antagonizing
      the injury of cochlear hair cells induced by GM ototoxicity,: and its
      disassembled prescriptions, Liuwei-Dihuang was the main component to protect the
      cochlear hair cells from GM-induced ototoxicity, and Magnetitum combined with
      Radix Bupleurui could strengthen the action of the whole prescription; Poria
      could reduce GM-induced OHC loss.

PMID- 20694783
TI  - Effect of treatment based on syndrome differentiation by Chinese medicine on post
      traumatic elbow arthritis.
AB  - OBJECTIVE: To compare the clinical efficacy of treatment based on syndrome
      differentiation of Chinese medicine and modern conservative therapeutic program
      on post-traumatic elbow arthritis (PTEA) in order to provide the guidance in
      clinical practice. METHODS: Seventy-six patients with PTEA requesting the
      conservative therapy were equally assigned to two groups randomly. The 38
      patients in the treated group were administered with Chinese herbal medicines
      according to their syndrome typing for oral intake and external washing; while
      the other 38 patients in the control group were treated orally with glucosamine
      hydrochloride and Celecoxib, combined with intra-articular injection of sodium
      hyaluronate and peri-articular pain spot blocking with Triamcinolone Acetonaide
      Acetate injection. All were followed-up for six months with the therapeutic
      efficacy assessed by Japanese Orthopaedic Association (JOA) and the Hospital for
      Special Surgery (HSS) Scale scoring. RESULTS: All the 76 patients completed the
      trial. The JOA and HSS scores in the two groups were not significantly different
      before treatment (P>0.05), but they did show significant difference after
      treatment in terms of total score, joint pain, range of motion, and daily
      activity (P<0.05). However, there was no difference between the two groups in the
      improvement of joint stability and deformity (P>0.05). CONCLUSION: Both the
      Chinese drug therapy according to syndrome differentiation and modern
      conservative therapy are effective in treating PTEA, but the former shows more
      superiority, and so it is worthy of clinical spreading.

PMID- 20694784
TI  - MS14, an Iranian herbal-marine compound for the treatment of multiple sclerosis.
AB  - MS14 is a natural herbal-marine drug, which has shown to slow down or halt the
      progression of multiple sclerosis (MS). This drug consists of 90% Penaeus
      latisculatus, 5% Apium graveolens, and 5% Hypericum perforatum L. Preclinically,
      the effects of MS14 have mostly been examined in an animal model of multiple
      sclerosis called experimental allergic encephalomyelitis (EAE). Clinical studies
      of the effects of MS14 in MS patients also showed that it could improve the
      patients' quality of life. MS14 is a safe drug in MS patients and might also be
      effective in the treatment of other neurodegenerative disorders with the same
      mechanisms.

PMID- 20694785
TI  - Magnetic resonance imaging of Alzheimer's disease: from diagnosis to therapeutic
      evaluation.
AB  - Alzheimer's disease (AD) is a devastating late-life dementia that produces
      progressive loss of memory and mental faculties in elderly people. It is
      important to identify the earliest evidence of AD and to monitor the development
      of this disease for us to make positive response to its management. Magnetic
      resonance imaging (MRI) is powerful to image the tissue or organ without
      damnification. MRI can be employed to diagnose the early AD development and
      monitor the key biomarker development in AD. MRI may be helpful not only in
      diagnosing early AD, but also in evaluating its development. This article reviews
      the progress of MRI on the diagnosis and detection of AD, and makes comments on
      its therapeutic application.

PMID- 20694786
TI  - Current progress of Chinese medicinal treatment of endometriosis.
AB  - Endometriosis (EM) is one of the common and frequently encountered gynecological
      diseases that seriously influences women's health. Its morbidity reaches 10%-15%
      in women at reproductive ages, and shows an evident rising tendency. In recent
      years, the Chinese medicine treatment of EM has won favorable therapeutic effects
      with few adverse reactions. A brief review on this topic has been made through
      analyzing and summarizing recent pertinent literatures in terms of treatment
      depending on syndrome differentiation, cycle treatment, external treatment,
      integrative medicinal treatment, so as to try to know the status quo of Chinese
      medicine treatment on EM, and to provide some instructive views for clinical
      treatment and research.

PMID- 20694787
TI  - [Intra-operative local tumor cell dissemination in rectal carcinoma surgery:
      effect of operation principles and neoadjuvant therapy].
AB  - BACKGROUND: The influence of surgical principles and neoadjuvant therapy on the
      frequency of local tumor cell dissemination (LTCD) in rectal carcinoma surgery
      and its consequences for local recurrence and survival rates were analyzed.
      PATIENTS AND METHODS: Data from the Erlangen registry for colorectal carcinomas
      (ERCRC) from 1969-2008 were compared with data from the literature published in
      1980-2008. RESULTS: LTCD was observed in 6.7% in the ERCRC (n=2764) and a
      frequency of 6.9% was reported in in the literature (n=13,395). In the course of
      time and especially since the introduction of total mesorectal excision (TME)
      surgery, the incidence of LTCD has significantly decreased. Neoadjuvant treatment
      did not influence the frequency of LTCD. Following LTCD the rate of local
      recurrence significantly increased and the 5 year survival rate significantly
      decreased. This also applied to patients with neoadjuvant therapy. CONCLUSIONS:
      Even in the era of TME surgery attention must to be paid to avoidance of LTCD. It
      is obligatory to document the occurrence of LTCD and it must be taken into
      consideration in routine quality assurance. In cases of LTCD postoperative
      chemoradiation is indicated for patients without neoadjuvant irradiation.

PMID- 20694789
TI  - [Cystic tumors of the pancreas].
AB  - Cysts of the pancreas most often develop after chronic or acute inflammation of
      the pancreas. Cystic neoplasia of the pancreas have been increasingly recognized
      in clinical practice and 90% are represented by four types: serous microcystic
      (SCN), mucinous cystic (MCN), intraductal papillary-mucinous (IPMN) and solid
      pseudopapillary (SPN) neoplasia. IPMN is the most common form nowadays and main
      duct and branch duct types can be differentiated by morphology. This
      classification is of prognostic and therapeutic relevance. While main duct IPMNs
      have a high risk of malignant progression and resection is therefore recommended,
      branch duct IPMNs have a much lower risk of harboring malignancy. Small branch
      duct IPMNs (<2 cm) without symptoms or mural nodules can be managed by periodic
      surveillance. Recently, it has become clear that IPMN constitutes a heterogeneous
      group with at least four subtypes. Their stratification reveals that the various
      subtypes of IPMN have different biological properties with different prognostic
      implications, but the subclassification is usually not known prior to surgery.
      Moreover, even differentiation between inflammatory and neoplastic cysts can be
      challenging. Clear indications for resection are local complications (jaundice or
      gastric outlet obstruction), large and increasing tumors, symptoms or secretion
      of mucinous fluid from the papilla of Vater.

PMID- 20694790
TI  - [Neurological aspects of chronic heart failure].
AB  - Chronic heart failure (CHF) is one of the leading causes of hospitalization,
      morbidity and mortality. Moreover, there is a high rate of neurological as well
      as neuropsychological comorbidities, namely ischemic stroke, structural brain
      alterations, cognitive impairment, sleep apnea and possible side-effects of HF
      medication such as delirium or (intracerebral) hemorrhage. The higher stroke risk
      in patients with HF increases further with age, concomitant arterial hypertension
      or atrial fibrillation (AF). In women the stroke risk increases with reduced
      ejection fraction (EF). In general stroke in HF patients is associated with a
      poor outcome and higher mortality, which is increased more than 2-fold.
      Furthermore, approximately 25-80% of all patients with CHF experience cognitive
      impairments such as decreased attention and concentration, memory loss,
      diminished psychomotor reaction time and decreased executive functions. Cognitive
      impairment in patients with HF has been linked to losses in gray matter, (silent)
      ischemic strokes, decreased cerebral perfusion and higher mortality. Moreover,
      sleep apnea occurs in more than half of all patients with CHF and reduced EF.
      However, prospective studies are needed to test whether early detection and
      optimal treatment of HF reduces the burden of neurological and neuropsychological
      sequelae.

PMID- 20694791
TI  - Quercetin restores plasma nitrite and nitroso species levels in renovascular
      hypertension.
AB  - Quercetin has antioxidants properties which may increase nitric oxide (NO)
      bioavailability. However, the effects of quercetin on NO status have been poorly
      studied. We evaluated whether quercetin improves the plasma levels of NO
      metabolites in two-kidney one-clip (2K1C) hypertensive rats and assessed its
      effect on endothelial function. Sham-operated and 2K1C rats were treated with
      quercetin (10 mg(-1) kg(-1) day(-1) by gavage) or vehicle for 3 weeks. Systolic
      blood pressure (SBP) was monitored weekly. Vascular responses to acetylcholine
      (Ach) and sodium nitroprusside (SNP) were assessed in hindquarter vascular bed.
      Plasma nitrate levels were assessed by Griess reagent and plasma nitrite and
      nitroso species (S, N-nitroso species) were assessed by ozone- based
      chemiluminescence. Aortic NADPH oxidase activity and superoxide production were
      evaluated. While quercetin had no effects in control normotensive rats (P >
      0.05), it significantly reduced SBP in 2K1C rats (P < 0.05). At the end of
      treatment, plasma nitrate levels were similar in all experimental groups (P >
      0.05). However, plasma nitrite and the nitroso species levels were significantly
      lower in 2K1C rats when compared with controls (P < 0.05). Quercetin treatment
      restored plasma nitrite and nitroso species levels to those found in the sham
      vehicle group (P < 0.05). While quercetin treatment induced no significant
      changes in responses to SNP (P > 0.05), it restored the vascular responses to
      Ach. Quercetin significantly attenuated 2K1C-hypertension-induced increases in
      NADPH oxidase activity and vascular superoxide production (P < 0.05). These
      results suggest that the antihypertensive effects of quercetin were associated
      with increased NO formation and improved endothelial function, which probably
      result from its antioxidant effects.

PMID- 20694792
TI  - Oxygen/ozone protects the heart from acute myocardial infarction through local
      increase of eNOS activity and endothelial progenitor cells recruitment.
AB  - The purpose of this study is to investigate whether an oxygen/ozone (O(2)/O(3))
      mixture protects the heart from acute myocardial infarction through local
      involvement of endothelial nitric oxide synthase (eNOS) and endothelial
      progenitor cells (EPCs). Male Sprague-Dawley rats were subject to 25-min
      occlusion and 2-h reperfusion of the left descending coronary artery. O(2)/O(3)
      mixture was insufflated i.p. 30 min prior to ischemia/reperfusion (I/R) procedure
      at doses of 100, 150, and 300 microg/kg. Myocardial infarct size (IS) measurement
      and myocardial immunohistochemistry for EPCs were done. For these latter cells,
      immunoreactivities for CD34, and CD117/c-kit were assessed within the infarcted
      tissue. Moreover, cardiac eNOS was monitored. I/R in rats treated with O(2)
      produced an IS as a percentage of the area at risk (IS/AR) equal to 51 +/- 5%.
      I/R in rats treated with the O(2)/O(3) mixture showed reduced IS (for example,
      IS/AR for 150 microg/kg O(2)/O(3) was 35 +/- 2.1%; P < 0.01 vs. O(2)). The
      O(2)/O(3) cardio-protection was paralleled by an increased number of
      immunopositive particles per area for CD34 and CD117/c-kit. The increase of these
      markers was associated with an increase of cardiac eNOS expression as assayed by
      immunohistochemistry. Interestingly, N5-(1-Iminoethyl)-L-ornithine
      dihydrochloride (L-NIO), a selective eNOS activity inhibitor (30 mg/kg s.c.),
      prior to O(2)/O(3) and I/R almost abolished the cardio-protection exerted by the
      O(2)/O(3) mixture. L-NIO also abolished the increase in immunostaining for CD-34
      and CD117/c-kit as compared with the rats receiving O(2)/O(3) and I/R only.
      O(2)/O(3) mixture protects the heart from acute myocardial infarction through
      local increase of eNOS expression/activity and consequent EPCs recruitment.

PMID- 20694793
TI  - Efficacy is a contributing factor to the clinical onset of bronchodilation of
      inhaled beta(2)-adrenoceptor agonists.
AB  - Inhaled beta(2) adrenoceptor (beta(2) AR) agonists are widely used as
      bronchodilator therapies for asthma and COPD. Different agonists have varying
      rates of onset of action, e.g. indacaterol and salbutamol are effective
      bronchodilators within 5 min whereas salmeterol takes 15 min to achieve
      significant bronchodilation over baseline (Brookman et al., Curr Med Res Opin
      23:3113-3122, 2007). This has been attributed to differences in the lipophilicity
      of the agonists such that hydrophobic ligands take longer to diffuse into tissue
      and may even access the receptor via the membrane compartment (Anderson et al.,
      Eur Respir J 7:569-578, 1994). While this holds true for salmeterol and
      salbutamol, the relatively high lipophilicity of indacaterol should result in a
      slower onset of action. Here we have explored the possibility that the efficacy
      of these ligands may also contribute to their onset of action. We have
      characterised efficacy and rate of cyclic adenosine monophosphate (cAMP)
      accumulation in primary human bronchial smooth muscle cells using a competition
      assay (AlphaScreen, Perkin Elmer) and in HEK 293-GloSensor cells endogenously
      expressing the beta(2) AR using a luminescence readout. For all agonists tested,
      cAMP was generated in a concentration-dependent manner. For both assay formats,
      the relative efficacies were unchanged, with isoprenaline > formoterol >
      indacaterol > salbutamol > salmeterol. The rate of cAMP generation varied for
      each agonist and correlated well with intrinsic efficacy in that the high
      efficacy agonists promoted the most rapid rise in cAMP levels. We have
      demonstrated that the rate of cAMP accumulation is influenced by agonist efficacy
      and that this, in combination with lipophilicity, may explain why beta(2) AR
      agonists demonstrate differences in their onset of action.

PMID- 20694794
TI  - Prevention of bacterial adhesion.
AB  - Management of bacterial infections is becoming increasingly difficult due to the
      emergence and increasing prevalence of bacterial pathogens that are resistant to
      available antibiotics. Conventional antibiotics generally kill bacteria by
      interfering with vital cellular functions, an approach that imposes selection
      pressure for resistant bacteria. New approaches are urgently needed. Targeting
      bacterial virulence functions directly is an attractive alternative. An obvious
      target is bacterial adhesion. Bacterial adhesion to surfaces is the first step in
      colonization, invasion, and biofilm formation. As such, adhesion represents the
      Achilles heel of crucial pathogenic functions. It follows that interference with
      adhesion can reduce bacterial virulence. Here, we illustrate this important topic
      with examples of techniques being developed that can inhibit bacterial adhesion.
      Some of these will become valuable weapons for preventing pathogen contamination
      and fighting infectious diseases in the future.

PMID- 20694795
TI  - Combined magnetic resonance imaging of deep venous thrombosis and pulmonary
      arteries after a single injection of a blood pool contrast agent.
AB  - OBJECTIVE: Agreement rate between magnetic resonance imaging (MRI) and Doppler
      ultrasound (DUS) for the detection of deep vein thrombosis (DVT) in the lower
      extremities was attempted by using the intravascular MRI contrast agent
      gadofosveset trisodium. The potential of this method to detect pulmonary embolism
      (PE) was also evaluated. MATERIAL AND METHODS: Forty-three consecutive inpatients
      with ultrasound-confirmed DVT but no clinical signs of PE were prospectively
      enrolled in this feasibility study. MRI was performed after a single injection of
      gadofosveset trisodium. The pulmonary arteries were imaged using a 3D Fast Low
      Angle Shot (FLASH) gradient recalled echo sequence. Additionally, pulmonary
      arteries, abdominal veins, pelvic and leg veins were imaged using a fat
      suppressed 3D gradient echo Volume Interpolated Breath-hold Examination (VIBE
      FS). RESULTS: Gadofosveset trisodium-enhanced MRI detected more thrombi in the
      pelvic region, upper leg and lower leg than the initial DUS. In addition, PE was
      detected in 16 of the 43 DVT patients (37%). CONCLUSION: This study shows the
      feasibility of a combined protocol for the MRI diagnosis of DVT and PE using
      gadofosveset trisodium. This procedure is not only more sensitive in detecting
      DVT compared to standard DUS, but is also able to detect PE in asymptomatic
      patients.

PMID- 20694796
TI  - Molecular pathology of human prion disease.
AB  - Human prion diseases are associated with a range of clinical presentations and
      are classified by both clinicopathological syndrome and aetiology with sub
      classification according to molecular criteria. Considerable experimental
      evidence suggests that phenotypic diversity in human prion disease relates in
      significant part to the existence of distinct human prion strains encoded by
      abnormal PrP isoforms with differing physicochemical properties. To date,
      however, the conformational repertoire of pathological isoforms of wild-type
      human PrP and the various forms of mutant human PrP has not been fully defined.
      Efforts to produce a unified international classification of human prion disease
      are still ongoing. The ability of genetic background to influence prion strain
      selection together with knowledge of numerous other factors that may influence
      clinical and neuropathological presentation strongly emphasises the requirement
      to identify distinct human prion strains in appropriate transgenic models, where
      host genetic variability and other modifiers of phenotype are removed. Defining
      how many human prion strains exist allied with transgenic modelling of
      potentially zoonotic prion strains will inform on how many human infections may
      have an animal origin. Understanding these relationships will have direct
      translation to protecting public health.

PMID- 20694797
TI  - Assessing the efficacy of targeted therapy using circulating epithelial tumor
      cells (CETC): the example of SERM therapy monitoring as a unique tool to
      individualize therapy.
AB  - PURPOSE: In malignant tumors, predictive markers have been developed with respect
      to targeted therapies. One of the first targeted therapies was the hormone
      blocking treatment of tumors of the male and female reproductive system. A
      typical therapy in breast cancer is the use of the selective estrogen receptor
      modulator, tamoxifen. However, only some of the patients, positive for the target
      molecules, respond to the selected therapy. It would, therefore, be highly
      desirable to have a tool to promptly assess the therapeutic efficacy of the
      applied agent in the individual patient. METHODS: Longitudinal observation of
      CETC provides a unique tool for monitoring therapy response. About 178 patients
      with breast cancer were followed prospectively during hormone therapy, requiring
      only 1 ml of peripheral blood, using a fluorochrome-labeled antibody against
      surface-epithelial antigen. Image analysis allowed CETC numbers to be calculated
      in relation to blood volume and monitoring over the entire course of treatment.
      RESULTS: A more than tenfold increase in CETC during therapy was a strong
      indicator of looming relapse (P = 0.0001 hazard ratio 5.5; 95% confidence
      interval 1,297-23,626), and a Cox regression analysis of age, tumor size,
      receptor expression, nodal status and previous treatment resulted in a regression
      model, in which CETC behavior was the parameter with the highest independent
      correlation to relapse-free survival. CONCLUSIONS: The change in the number of
      CETC (increase or decrease) may, in the future, be used to guide therapy in order
      to change to other available treatment options in good time.

PMID- 20694798
TI  - Single-dose palonosetron for prevention of chemotherapy-induced nausea and
      vomiting in patients with aggressive non-Hodgkin's lymphoma receiving moderately
      emetogenic chemotherapy containing steroids: results of a phase II study from the
      Gruppo Italiano per lo Studio dei Linfomi (GISL).
AB  - PURPOSE: The control of nausea and vomiting induced by chemotherapy is paramount
      for overall treatment success in cancer patients. Antiemetic therapy during
      chemotherapy in lymphoma patients generally consists of anti-serotoninergic drugs
      and dexamethasone. The aim of this trial was to evaluate the efficacy of a single
      dose of palonosetron, a second-generation serotonin type 3 (5-HT(3)) receptor
      antagonist, in patients with aggressive non-Hodgkin's lymphoma receiving
      moderately emetogenic chemotherapy (MEC) containing steroids. METHODS: Patients
      received a single intravenous bolus of palonosetron (0.25 mg) before
      administration of chemotherapy. Complete response (CR) defined as no vomiting and
      no rescue therapy during overall phase (0-120 h) was the primary endpoint.
      Complete control (CC) defined as CR and only mild nausea was a secondary
      endpoint. RESULTS: Eighty-six evaluable patients entered in the study. A CR was
      observed in 74 patients (86.0%) during the overall phase; the CR during the acute
      (0-24 h) and delayed (24-120 h) phases was 90.7% and 88.4%, respectively. CC was
      89.5% during the acute and 84.9% during the delayed phase; the overall CC was
      82.6%. CONCLUSIONS: This was the first trial, which demonstrated the efficacy of
      a single dose of palonosetron in control CINV in patients with aggressive non
      Hodgkin's lymphoma receiving MEC regimen containing steroids.

PMID- 20694799
TI  - Internal herniation of the anterior gastric wall through an attenuated Nissen
      Fundoplication wrap: an unusual complication and its laparoscopic management.
AB  - Laparoscopic Nissen fundoplication is the treatment of choice for medically
      refractive gastro-oesophageal reflux disease as it is considered safe, cost
      efficient and effective. Unusual variants of internal abdominal herniation,
      however, have been reported after the procedure. Here, we present a case of a 38
      year-old woman who presented 3 months after a successful laparoscopic Nissen
      Rossetti fundoplication, with abdominal pain and persistent vomiting. Abdominal X
      ray at the time of admission was normal but CT suggested internal herniation of
      the stomach. Laparoscopy confirmed internal herniation of the anterior wall of
      the stomach through an attenuated fundoplication wrap. We show that a prompt
      diagnosis of this complication, which we have not found reported previously in
      the English literature, can be achieved by CT, permitting an early laparoscopic
      intervention to preserve the viability of the obstructed segment of stomach.

PMID- 20694800
TI  - High dose methotrexate for pediatric high grade glioma: results of the HIT-GBM-D
      pilot study.
AB  - We conducted a phase II study to test methotrexate (5 g/m(2)), as a single agent
      prior to radiochemotherapy for pediatric high-grade glioma and diffuse intrinsic
      pontine glioma. Thirty patients (19 male, median age 10.8) were enrolled. Tumors
      were located as follows: cortex 10, pons 7, other 13. Tumor resection was
      classified as gross total in 6, subtotal in 6, partial in 4, biopsy in 11 and not
      performed in 3. WHO grading of the histology was: IV: 11, III: 12 and II: 3.
      Patients received methotrexate 5 g/m(2) in 24-hour infusions on days 1 and 15.
      Subsequently 54 Gy radiation was administered with simultaneous chemotherapy
      including cisplatin, etoposide, vincristine and ifosfamide as previously
      described. Eight 6-weeks cycles of maintenance chemotherapy consisted of
      vincristine 1.5 mg/m(2) on days 1, 8 and 15; lomustine 100 mg/m(2) on day 2 and
      prednisone 40 mg/kg on days 1-17. Event-free survival rates in the whole group of
      30 patients were: 43, 20, and 13% after 1, 2 and 5 years, respectively. The
      response evaluation after methotrexate was available in 19 of the 24 patients who
      started treatment with measurable disease: CR: 0, PR: 1, SD 18, PD: 0. After
      radiochemotherapy the response of 24 patients with measurable disease was CR: 1,
      PR 10, SD 12, PD 1. Both response and event-free survival were superior to the
      control group of 330 patients treated in various protocols of the same
      cooperative group. In subgroup analyses the use of dexamethasone during early
      treatment was linked to poor event free survival. Giving two cycles of high-dose
      methotrexate prior to radiochemotherapy was feasible, and the approach was taken
      forward to a randomized phase III trial.

PMID- 20694801
TI  - An integrated pharmacokinetic-pharmacodynamic model for an Aurora kinase
      inhibitor.
AB  - The spindle assembly checkpoint is a cell cycle surveillance mechanism that
      ensures the proper separation of chromosomes prior to cell division at mitosis.
      Aurora kinases play critical roles in mitotic progression and hence small
      molecule inhibitors of Aurora kinases have been developed as a new class of
      potential anti-cancer drugs. In this paper we present for the first time an
      integrated pharmacokinetic-pharmacodynamic model of the functional effects of
      CYC116 (a known inhibitor of Aurora kinases A and B) on the spindle assembly
      checkpoint. We use the model to simulate two common experimental systems: cell
      culture and p.o. dosing of mice and present predictions of the effects of CYC116
      for a range of doses and drug scheduling regimes. The model reveals that a
      critical peak drug concentration is required to cause aberrant kinetochore
      microtubule attachments. The model also predicts that provided this threshold
      concentration is exceeded, a high total oral dose causes a high number of
      aberrant attachments within any given damaged cell. However, the proportion of
      cells which enter anaphase with aberrant attachments is associated with the total
      length of time for which the plasma concentration is maintained above the
      threshold. Moreover, our model reveals that the length of prometaphase/metaphase
      is a nonlinear function of drug dose and this time period can be extended or
      shortened. Finally, a strong saturation effect on CYC116 efficacy is predicted by
      the model. We discuss how these predictions may have implications for further
      drug trials using CYC116 and other similar AK inhibitors.

PMID- 20694802
TI  - The effectiveness of a community-based intervention program for women at-risk for
      giving birth to a child with Fetal Alcohol Spectrum Disorder (FASD).
AB  - The goal of this study was to determine whether the First Steps program (modeled
      after the Parent-Child Assistance Program) resulted in improved outcomes among
      women at-risk for giving birth to a child with FASD. We conducted a retrospective
      analysis of data on 70 participants in the First Steps program. Clients were high
      risk and faced many life challenges, including: being on welfare, substance
      abuse, physical and sexual abuse as children, mental health issues, criminal
      activity, and unplanned pregnancies. We found a significant increase in birth
      control use and decrease in welfare rates from pre- to post-program. At program
      exit, many participants were abstinent from alcohol and/or drugs and the majority
      did not experience a subsequent pregnancy. Clients also showed significant
      increases in goals and decreases in needs from pre-to post-program. The First
      Steps program demonstrated promising outcomes for women at-risk for giving birth
      to a child with FASD.

PMID- 20694804
TI  - Abstracts of the UCD School of Medicine and Medical Science (SMMS) Summer Student
      Research Awards. October 7, 2009. Dublin, Ireland.

PMID- 20694803
TI  - Solitary pulmonary nodules: consequences for patient quality of life.
AB  - PURPOSE: The aim was to describe levels of health-related quality of life (HRQoL)
      and its determinants in patients with solitary pulmonary nodule (SPN) and to
      compare them with the French general population. METHODS: A prospective
      multicentre study of patients diagnosed with SPN, in northeastern regions of
      France, was carried out between 2002 and 2005. Six months after the end of
      diagnostic procedure, patients completed the SF-36 self-reported questionnaire
      (where 100 indicates high HRQoL). For a comparison, HRQoL data from a sample of
      the French general population collected by INSEE in 2002-2003 (n = 17,750).
      RESULTS: Among 171 participating patients, 39 had malignant nodules and had
      lesser mean scores on physical and emotional role, vitality and social
      functioning (-6 to -18 points) than those with nonmalignant nodule. Compared to
      the French general population, patients with SPN had lower scores, by 11-30
      points, in all dimensions (P < 0.001). Older age and smoking history were
      associated with low HRQoL. CONCLUSIONS: Six months after receiving a diagnosis of
      SPNs, whether malignant, patients have worse HRQoL compared to the French general
      population. It indicates areas where physicians can help patients coping with
      their disease.

PMID- 20694805
TI  - Effectiveness of thrombolysis in patients with intermediate-risk pulmonary
      embolism: influence on length of hospital stay.
AB  - INTRODUCTION: The effects of thrombolysis on the clinical outcome of patients
      with intermediate-risk pulmonary embolism (PE) are still under debate. The effect
      of thrombolysis on the length of stay (LOS) in hospital is unknown. The aim of
      this study was to identify factors associated with LOS and to investigate whether
      LOS is suitable to assess effectiveness of thrombolysis in patients with
      intermediate-risk PE. METHODS: Data were reviewed from December 2005 until
      October 2009. The LOS in the intensive care unit (ICU) was expressed in hours,
      and total LOS was recorded in days. Total LOS was not noted in case of preterm
      withdrawal of therapy or death. RESULTS: Of a total of 202 patients, 84 received
      alteplase plus heparin and 118 patients were treated with anticoagulants alone.
      Total median LOS was significantly shorter (10 vs. 12 days) in the alteplase
      group (P=0.005), while there was no difference in the LOS in the ICU. Age above
      65 years (P=0.036) and comorbidity (P<0.001) were independent predictors for a
      prolonged hospital stay, whereas thrombolysis independently predicted a shorter
      total LOS in multivariate analysis (P=0.001). Thrombolysis has shown to be able
      to independently predict home discharge (P=0.029). CONCLUSION: LOS is influenced
      by patient-related factors such as age and comorbidity. Thrombolysis may lead to
      a reduction of total median LOS for patients with intermediate-risk PE, possibly
      indicating that it is more effective than anticoagulant therapy alone in this
      group of patients.

PMID- 20694806
TI  - Quantitative analysis of cycloartane glycosides in black cohosh rhizomes and
      dietary supplements by RRLC-ELSD and RRLC-qTOF-MS.
AB  - In this study, a fast and reproducible RRLC-ELSD method for the quantitative
      analysis of 17 cycloartane glycosides and the aglycone cimigenol in black cohosh
      rhizomes and dietary supplements has been developed. Separation of the 18
      triterpenes was achieved within 16 min using reversed phase material and a
      gradient elution system consisting of water, acetonitrile and methanol. The
      method was validated for accuracy (recovery rates from 96.79% to 102.86%),
      precision (intra-day variation <=5.98%, inter-day variation <=3.74%),
      repeatability (R.S.D. <= 6.94%) and sensitivity, with detection limits below 4.0
      MUg/mL and quantification limits lower than 13.2 MUg/mL. Calibration curves were
      established in the range from 5-1,000 MUg/mL, with correlation coefficients
      higher than 0.998 for all constituents investigated. Peak purity and peak
      assignment were confirmed by means of RRLC-qTOF-MS and in comparison with
      reference compounds. Three different MS sources (ESI, APCI and APPI) were
      compared for their ionisation potential regarding cycloartane derivatives. One of
      the isolated black cohosh constituents, 24-O-acetylhydroshengmanol-3-O-alpha-L
      arabinopyranoside, could be identified as new natural compound.

PMID- 20694807
TI  - Thin-layer chromatography combined with MALDI-TOF-MS and 31P-NMR to study
      possible selective bindings of phospholipids to silica gel.
AB  - High-performance thin-layer chromatography (HPTLC) is a highly established
      separation method in the field of lipid and (particularly) phospholipid (PL)
      research. HPTLC is not only used to identify certain lipids in a mixture but also
      to isolate lipids (preparative TLC). To do this, the lipids are separated and
      subsequently re-eluted from the silica gel. Unfortunately, it is not yet known
      whether all PLs are eluted to the same extent or whether some lipids bind
      selectively to the silica gel. It is also not known whether differences in the
      fatty acyl compositions affect the affinities to the stationary phase. We have
      tried to clarify these questions by using a readily available extract from hen
      egg yolk as a selected example of a lipid mixture. After separation, the complete
      lanes or selected spots were eluted from the silica gel and investigated by a
      combination of MALDI-TOF MS and (31)P NMR spectroscopy. The data obtained were
      compared with the composition of the total extract (without HPTLC). Although
      there were significant, solvent-dependent losses in the amount of each lipid, the
      relative composition of the mixture remained constant; there were also only very
      slight changes in the fatty acyl compositions of the individual PL classes.
      Therefore, lipid isolation by TLC may be used without any risk of major sample
      alterations.

PMID- 20694808
TI  - Simultaneous determination of ochratoxin A, mycophenolic acid and fumonisin B(2)
      in meat products.
AB  - Here we present a method for simultaneous determination of the fungal metabolites
      mycophenolic acid, ochratoxin A (OTA) and fumonisin B(2) (FB(2)) in meat
      products. Extraction was performed with water-acetonitrile, followed by acetone
      induced precipitation of salts and proteins. Purification and identification of
      analytes was performed by mixed-mode reversed-phase anion-exchange chromatography
      in direct ion-exchange mode, followed by liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) detection. Quantification was based on isotope dilution
      with fully (13)C-labelled FB(2) and OTA, and matrix-spiked calibration curves.
      Fermented sausages inoculated with an OTA- and FB(2)-producing strain of
      Aspergillus niger were analysed, but no analytes were detected. Analysis of 22
      retail products showed one Parma meat with a very high level of OTA contamination
      (56-158 microg/kg) that clearly exceeded the Italian regulatory limit of 1
      microg/kg. This sample and uninfected control samples were subsequently
      reanalysed, and the high OTA content was verified by two other techniques: (i) LC
      time-of-flight MS confirmed the accurate mass as well as chlorine isotope
      pattern; and (ii) sample methylation in methanol-BF(3) and subsequent LC-MS/MS
      provided indirect confirmation by detection of the OTA methyl ester. In the
      contaminated Parma ham, the high OTA level most likely originated from growth of
      Penicillium nordicum on the meat.

PMID- 20694809
TI  - Quantum dots for positional registration in live cell-based arrays.
AB  - For a better understanding of complex biological processes, it is desirable to
      simultaneously follow the dynamics of multiple components in living cells or
      organisms in real time. An encoding scheme was developed that enables the
      observation of multiple cell populations with single-cell resolution.
      Specifically, different yeast cell types were labeled with quantum dots and added
      to an array of microwells, where they randomly self-assemble into the
      complementary-sized cavities. Quantum dots conjugated to cells externally,
      internally, or in combination generated unique optical patterns to differentiate
      various cell types in the array. For the model system described herein, cells
      were monitored for their lacZ expression levels through the processing of a
      fluorescent precursor by ss-galactosidase. The encoding schemes employed were
      independent of the reporter emission and had no affect on the cellular activity.
      The live cell array platform allowed analysis of hundreds of individual cells
      simultaneously and continuously in real time. By coupling this platform with
      quantum dot cell labeling, the utility of this array format is extended to mixed
      cellular populations.

PMID- 20694810
TI  - A compact miniaturized continuous flow system for the determination of urea
      content in milk.
AB  - A multicommutation-based flow system with photometric detection was developed,
      employing an analytical microsystem constructed with low temperature co-fired
      ceramics (LTCC) technology, a solid-phase reactor containing particles of
      Canavalia ensiformis DC (urease source) immobilized with glutaraldehyde, and a
      mini-photometer coupled directly to the microsystem which monolithically
      integrates a continuous flow cell. The determination of urea in milk was based on
      the hydrolysis of urea in the solid-phase reactor and the ammonium ions produced
      were monitored using the Berthelot reaction. The analytical curve was linear in
      the urea concentration range from 1.0 x 10(-4) to 5.0 x 10(-3) mol L(-1) with a
      limit of detection of 8.0 x 10(-6) mol L(-1). The relative standard deviation
      (RSD) for a 2.0 x 10(-3) mol L(-1) urea solution was lower than 0.4% (n = 10) and
      the sample throughput was 13 h(-1). To check the reproducibility of the flow
      system, calibration curves were obtained with freshly prepared solutions on
      different days and the RSD obtained was 4.7% (n = 6). Accuracy was assessed by
      comparing the results of the proposed method with those from the official
      procedure and the data are in close agreement, at a 95% confidence level.

PMID- 20694811
TI  - Dried plasma spots as an alternative sample collection technique for the
      quantitative LC-MS/MS determination of gabapentin.
AB  - Dried plasma spots were employed as an alternative sample collection technique
      for the quantitative determination of gabapentin in human plasma, using an
      automated liquid chromatography tandem mass spectrometry method. After the
      methanolic extraction of single plasma, 1/8-in. disks which contained only 1.98
      microL plasma volume, were placed in 96-well format plates, then gabapentin and
      its internal standard, 4-aminocyclohexanecarboxylic acid, were derivatized with n
      butanol/HCl (3 M) and detected as butyl esters. The assay exhibited excellent
      linearity over the concentration range of 40.0-10.0 x 10(3) ng/mL, which is
      suitable for the determination of gabapentin after per os administration of a
      single tablet. Variations in intra- and inter-assay accuracy and precision were
      within internationally accepted criteria. Homogeneity of plasma spots was proven,
      whilst butyl ester stability for both analytes was estimated and found very
      satisfactory. The quantitative analysis of Gabapentin with dried plasma spot
      specimens seems to be a prominent and advantageous technique, especially when
      applied to pharmacokinetic studies, where plasma sampling procedure becomes rapid
      and required plasma volumes negligible.

PMID- 20694812
TI  - Response surface optimization for determination of pesticide residues in grapes
      using MSPD and GC-MS: assessment of global uncertainty.
AB  - In this work, a simple and low-cost method based on matrix solid-phase dispersion
      (MSPD) and gas chromatography to determine eight multi-class pesticides such as
      vinclozolin, dichlofluanid, penconazol, captan, quinoxyfen, fluquinconazol,
      boscalid, and pyraclostrobin in grapes is described. Fungicide residues were
      identified and quantified using gas chromatography-mass spectrometry in selected
      ion monitoring mode (GC-MS, SIM). The experimental variables that affect the MSPD
      method, such as the amount of solid phase, solvent nature and elution volume were
      optimized using an experimental design. The best results were obtained using 0.5
      g of grapes, 1.0 g of silica as clean-up sorbent, 1.50 g of C(18) as bonded phase
      and 10 mL of dichloromethane/ethyl acetate (1:1, v/v) as eluting solvent.
      Significant matrix effects observed for most of the pesticides tested were
      eliminated using matrix-matched standards. The pesticide recoveries in grapes
      samples were better than 80% except for captan. Intra-laboratory precision in
      terms of Horwitz ratio of the pesticides evaluated was below 0.5, suggesting
      ruggedness of the method. The quantification limits of the pesticides were in the
      range of 3.4-8.7 microg kg(-1), which were lower than the maximum residue limits
      (MRLs) of the pesticides in grapes samples established by the European
      legislation. Decision limits (CCalpha) and detection capability (CCbeta) have
      been calculated. The expanded uncertainties at two levels of concentration were
      <20% for all analytes.

PMID- 20694813
TI  - Monitoring of troponin release from cardiomyocytes during exposure to toxic
      substances using surface plasmon resonance biosensing.
AB  - Troponin T (TnT) is a useful biomarker for studying drug-induced toxicity effects
      on cardiac cells. We describe how a surface plasmon resonance (SPR) biosensor was
      applied to monitor the release of TnT from active HL-1 cardiomyocytes in vitro
      when exposed to cardiotoxic substances. Two monoclonal human TnT antibodies were
      compared in the SPR immunosensor to analyse the TnT release. The detection limit
      of TnT was determined to be 30 ng/ml in a direct assay set-up and to be 10 ng/ml
      in a sandwich assay format. Exposure of the cardiomyocytes to doxorubicin,
      troglitazone, quinidine and cobalt chloride for periods of 6 and 24 h gave
      significant SPR responses, whereas substances with low toxicity showed
      insignificant effects (ascorbic acid, methotrexate). The SPR results were
      verified with a validated immunochemiluminescence method which showed a
      correlation of r (2) = 0.790.

PMID- 20694814
TI  - Determination of antibacterials in animal feed by pressurized liquid extraction
      followed by online purification and liquid chromatography-electrospray tandem
      mass spectrometry.
AB  - A fully automated method has been developed for analysis of eighteen
      antibacterial compounds, including penicillins, cephalosporins and sulfonamides,
      in animal feed with limits of quantification in the range 0.25-5.79 microg kg(
      1). The method is based on pressurized liquid extraction of 3 g homogenized feed
      with water and online clean-up of 500 microL of the extract with C(18)HD
      cartridges. The purified sample was directly analysed by liquid chromatography
      electrospray tandem mass spectrometry (SPE-LC-ESI-MS-MS). Chromatographic
      separation was achieved within 10 min by use of a C(12) Phenomenex Hydro-RP
      reversed-phase analytical column and a mobile phase gradient (water + 0.1% formic
      acid-methanol + 0.1% formic acid). The method was validated, revealing capability
      for detection of concentrations as low as 0.09 microg kg(-1), decision limits
      (CCalpha) and detection capabilities (CCbeta) in the range 10-174 microg kg(-1)
      and 22-182 microg kg(-1), respectively, and inter-day precision ranging from 0.7
      to 8.3%. Recovery, with internal standard correction, was in the range 93-134%
      for all analytes. The method was then applied to analysis of fifteen feed
      samples, nine of which contained at least one antimicrobial at concentrations
      between 0.006 and 1.526 mg kg(-1). The performance data and results from the
      method were compared with those from a previous method developed by our group,
      using offline SPE, by analyzing the same set of samples by both methods. The
      online SPE approach resulted in slightly improved sensitivity, with LODs of 0.09
      2.12 microg kg(-1) compared with 0.12-3.94 microg kg(-1) by the offline approach.
      In general, better recovery was achieved by use of online purification (for 72%
      of the analytes) and the correlation between the two methods was good. The main
      advantages of the new online method are rapid and automated sample pre-treatment,
      and reduction of sample manipulation, enabling high-throughput analysis and
      highly accurate results. Because of all these characteristics, the proposed
      method is applicable and could be deemed necessary within the field of food
      control and safety.

PMID- 20694815
TI  - Stability of Abeta (1-42) peptide fibrils as consequence of environmental
      modifications.
AB  - beta-Amyloid peptide (Abeta) plays a key role in the pathogenesis of Alzheimer
      disease (AD). Monomeric Abeta undergoes aggregation, forming oligomers and
      fibrils, resulting in the deposition of plaques in the brain of AD patients. A
      widely used protocol for fibril formation in vitro is based on incubation of the
      peptide at low pH and ionic strength, which generates Abeta fibrils several
      microns long. What happens to such fibrils once they are brought to physiological
      pH and ionic strength for biological studies is not fully understood. In this
      investigation, we show that these changes strongly affect the morphology of
      fibrils, causing their fragmentation into smaller ones followed by their
      aggregation into disordered structures. We show that an increase in pH is
      responsible for fibril fragmentation, while increased ionic strength is
      responsible for the aggregation of fibril fragments. This behavior was confirmed
      on different batches of peptide either produced by the same company or of
      different origin. Similar aggregates of short fibrils are obtained when monomeric
      peptide is incubated under physiological conditions of pH and ionic strength,
      suggesting that fibril morphology is independent of the fibrillation protocol but
      depends on the final chemical environment. This was also confirmed by experiments
      with cell cultures showing that the toxicity of fibrils with different initial
      morphology is the same after addition to the medium. This information is of
      fundamental importance when Abeta fibrils are prepared in vitro at acidic pH and
      then diluted into physiological buffer for biological investigations.

PMID- 20694816
TI  - Ultrasound-guided percutaneous injection of triamcinolone acetonide for treating
      capsular contracture in patients with augmented and reconstructed breast.
AB  - OBJECTIVES: To evaluate ultrasound (US)-guided treatment of capsular contracture
      (CC) in patients with reconstructed/augmented breast. METHODS: Twenty-five
      patients with grade IV CC were treated with peri-implant US-guided injection of
      triamcinolone acetonide. Before/after treatment, maximum capsular thickness (MCT)
      was measured by ultrasound and pain assessed with visual analogue score (pain
      VAS). Patients with pain relief at 1 month were considered early responders
      (ERs). Another injection was performed in patients without pain relief at 1 month
      (late responders, LRs). RESULTS: One patient (treated with chemo-radiotherapy)
      experienced severe pain and local reaction after the second injection, requiring
      surgery. Twenty-four patients had baseline MCT of 1.8 +/- 0.3 mm and pain-VAS of
      4.9 +/- 0.5, the baseline MCT of 19 ERs (1.7 +/- 0.2 mm) being significantly
      lower than that of 5 LRs (2.1 +/- 0.2 mm) (p = 0.030). ERs had significantly
      reduced MCT and pain-VAS at one (1.1 +/- 0.3 mm; 1.5 +/- 0.5) and 6 months (1.1
      +/- 0.2 mm; 0.9 +/- 0.7, respectively) (p < 0.001). At 1 month, LRs had a
      significantly reduced MCT (1.6 +/- 0.1 mm, p = 0.042) but non-significantly
      changed pain-VAS (4.7 +/- 0.2); 5 months later, MCT reached 1.0 +/- 0.1 mm, pain
      VAS reached 0.8 +/- 0.5 (p < 0.044). Significant correlation between the relative
      variation of MCT and pain-VAS (1 month/baseline) was found. CONCLUSIONS: US
      guided injection of triamcinolone acetonide is effective in treating grade IV CC.

PMID- 20694817
TI  - Characterization of ex vivo healthy human axillary lymph nodes with high
      resolution 7 Tesla MRI.
AB  - OBJECTIVE: To characterize ex vivo healthy human axillary lymph nodes on 7 Tesla
      MRI and to correlate the findings with pathological analysis as a first step
      towards non-invasive staging of breast cancer patients in the future. METHODS:
      Four axillary lymph node dissection (ALND) specimens from 2 autopsy patients, who
      had no cancer, were examined on a clinical 7 Tesla MRI system. For morphological
      analysis a 3D T1-weighted fat-suppressed fast-field-echo [isotropic resolution
      180 MUm] was acquired. For quantitative analyses 2D T1-, 3D T2-, T2*- and
      diffusion-weighted images were acquired. The ALNDs were mapped and stained for
      precise correlation of MRI to pathology. Nodes were sliced in 3 MUm sections,
      Haematoxylin & Eosin stained, and examined by an experienced pathologist.
      RESULTS: MRI detected all 45 nodes and 6 additional nodes that were not detected
      at pathological analysis. B-cell follicles, efferent- and afferent lymph vessels
      and blood vessels were identified. Mean T1, T2, T2*, ADC values (+/- standard
      deviation) were 944 +/- 113 ms, 32 +/- 2 ms, 16 +/- 2 ms, 0.39 +/- 0.09.10-3
      mm2/s, respectively. CONCLUSIONS: 7 Tesla MRI of ex vivo human axillary lymph
      nodes correlated well with pathology. MRI detected all nodes present in the
      specimens and allowed visualization of fine structural detail. Pathology
      correlated quantitative MRI data are presented.

PMID- 20694818
TI  - Keiichi Maruyama MD, professor of surgery, Tokyo.

PMID- 20694819
TI  - Transient hyperoxaluria in a patient with inherited distal renal tubular
      acidosis.

PMID- 20694820
TI  - Parathyroid hormone and growth in chronic kidney disease.
AB  - Growth failure is common in children with chronic kidney disease, and successful
      treatment is a major challenge in the management of these children. The aetiology
      is multi-factorial with "chronic kidney disease-metabolic bone disorder" being a
      key component that is particularly difficult to manage. Parathyroid hormone is at
      the centre of this mineral imbalance, consequent skeletal disease and,
      ultimately, growth failure. When other aetiologies are treated, good growth can
      be achieved throughout the course of the disease when parathyroid hormone (PTH)
      levels are in the normal range or slightly elevated. A direct correlation between
      PTH levels and growth has not been convincingly established, and the direct
      effect of PTH on growth has not been adequately described; furthermore, direct
      actions of PTH on the growth plate are unproven. The effects of PTH on growth
      stem from the pivotal role that PTH plays in the development of renal
      osteodystrophy. In severe secondary hyperparathyroidism, the growth plate is
      altered and growth is affected. At the other end of the spectrum, with an over
      suppressed parathyroid gland, the rate of bone turnover and remodelling is
      markedly diminished, and some data suggest this is associated with poor growth.
      Most of the data available suggests that avoiding the development of significant
      bone disease through the strict control of PTH levels permits good growth.
      Absolute optimal ranges for PTH that maximise growth or minimise growth failure
      are not yet established.

PMID- 20694821
TI  - Cancer patients' informational needs on health promotion and related factors: a
      multi-institutional, cross-sectional study in Korea.
AB  - BACKGROUND: As the survival rates of cancer patients increase, health promotion
      for cancer survivors becomes a more important issue. This study examines whether
      the informational needs on health promotion by cancer patients is being met and
      evaluates other factors associated with those informational needs. METHODS:
      Questionnaires were collected from a total of 2,661 cancer patients at ten cancer
      centers in Korea from July to August 2008. The questionnaire was designed to
      elicit informational needs related to healthy behaviors, nutrition, and
      complementary and alternative medicine (CAM). Multiple logistic regression models
      were developed to identify factors affecting the informational needs of cancer
      survivors regarding health promotion. RESULTS: In our study sample, we found that
      64.83%, 66.38%, and 47.40% of patients have unmet informational needs regarding
      healthy behaviors, nutrition, and CAM, respectively. The desire for information
      about health promotion appears to be related to socio-demographic factors,
      clinical factors, behavioral factors, and quality of life. Younger patients with
      higher levels of education, shorter time since diagnosis, greater stress levels,
      previous experience using CAM, and problems identified on EQ5D expressed greater
      needs for health-related information. Cancer recurrence and smoking status were
      also associated with greater informational needs about nutrition and CAM.
      CONCLUSIONS: A significant proportion of cancer patients have unmet informational
      needs on health promotion. We identified several factors that influence the
      desire for more health-related information. A tailored approach to providing
      informational resources to patient groups with unmet informational needs is
      recommended to enhance the quality of life of cancer patients.

PMID- 20694822
TI  - Is education an effective management strategy for reducing cancer-related
      fatigue?
AB  - PURPOSE: The use of education is recommended to teach patients self-care
      behaviours to reduce cancer-related fatigue, however, there is little evidence of
      its effectiveness or optimal timing. This educationally based cancer-related
      fatigue intervention trial, CAN-FIT, aimed to reduced severity of fatigue in
      radiotherapy patients. METHODS: One hundred and ten participants aged>=18 years
      undergoing curative radiotherapy were randomly assigned to receive (1) pre- and
      post-radiotherapy fatigue education and support (RFES); (2) pre-RFES only; (3)
      post-RFES only; or (4) no RFES (standard care). Data collection occurred at pre-
      and post- radiotherapy and at 6-weeks follow-up. RESULTS: The intervention was
      not associated with reduction in fatigue levels at any assessment point.
      Significant changes were seen with secondary activity-based outcomes: Physical
      activity participation: Pre-RFES was associated with significantly greater
      increase in vigorous [Assessment (Ax)1-Ax2: 1.05 (0.24, 1.86) p<0.01: Ax2-Ax3:
      1.24, (0.44, 2.03) p<0.01] and moderate physical activity participation [Ax1-Ax2:
      1.4 (0.53, 2.26) p<0.01]. Post-RFES was associated with significant improvements
      in walking levels [Ax1-Ax3: 5.82 (0.07, 11.56) p<0.05] compared with no pre-RFES.
      Paid and unpaid employment: Pre-RFES was associated with slower return to pre
      treatment levels of paid work [Ax2-Ax3: -0.72 (-1.41, -0.04) p<0.05] than no pre
      RFES. Post-RFES was associated with decreased levels of unpaid work [Ax1-Ax3:
      561.79 (51.21, 1,072.37) p<0.05] compared with no post-RFES. CONCLUSION: The CAN
      FIT programme did not significantly improve the primary outcome, level of
      fatigue, regardless of when it was delivered, however, significant changes were
      observed in activity-based outcomes. Further investigations into educationally
      based programmes should target activity participation rather than changes in
      underlying fatigue to improve overall patient health.

PMID- 20694823
TI  - Clinical use of oral laxatives in palliative care services in Spain.
AB  - OBJECTIVES: This study was aimed at evaluating the clinical use of laxatives in
      palliative care treatment, their overall effectiveness, and their relationship to
      opioid treatment. POPULATION AND METHOD: A cross-sectional prospective study on
      patients attended by 21 palliative care teams on two pre-determined dates was
      carried out. The variables analyzed were demographic data, underlying disease,
      functional status, laxative use, use of enemas, concomitant opioid medication,
      and bowel movements. RESULTS: Of the 283 patients studied, 54 (19%) have had
      three or fewer bowel movements per week in the 3 weeks prior to the study, 53
      patients (19%) were using rectal measures, 177 patients (63%) were being treated
      with opioids, and 164 patients (58%) were taking laxatives. Sixty seven percent
      (119/177) of the patients being treated with opioids were also being treated with
      laxatives, as were 43% (45/106) of those not receiving opioid treatment. The
      laxative most used was lactulose (65%). Only 10% used the most recommended
      combination of an osmotic or softener laxative mixed with another stimulant
      laxative. Some 24% of patients used enemas or micro enemas in addition to
      laxatives, 14 patients treated their constipation without laxatives, using only
      rectal measures. CONCLUSION: The clinical practice of the use of oral laxatives
      in palliative care in our environment differs widely from that recommended in the
      literature. Further studies are required to confirm if a revision of clinical
      guidelines are required.

PMID- 20694824
TI  - Wavesense technology glucometer Linus for routine self-monitoring and clinical
      practice.
AB  - Conventional glucometer systems for plasma/blood glucose monitoring are based on
      colorimetry or static electrochemistry using a fixed input signal. The recent
      glucometer Linus, Wellion, Agamatrix, USA, based on wavesense dynamic
      electrochemistry, uses a time-varying input signal to give a more accurate
      glucose reading. The purpose of this study was to compare the plasma glucose (PG)
      readings obtained by nursing staff from glucometer Linus and PG values estimated
      on an approved analyzer DaytonaTM, Randox, Global Medical Instrumentation, Inc.,
      MN, USA. In the course of 5 weeks, 221 fingerprick capillary blood samples were
      taken from persons with diabetes at different times and investigated using
      glucometer Linus. Within two following minutes, blood from the same fingerprick
      was also collected in a tube and centrifuged; the plasma was analyzed on the
      DaytonaTM analyzer. Statistical analysis was performed using the software SPSS v.
      15.0, SPSS Inc., Chicago, IL, USA. A total of 221 paired PG values were plotted
      on the error grid diagram indicating that 218 values (98.6%) of the glucose
      readings (Linus vs. Daytona) were within the clinically accurate zone A (maximum
      difference +/-20%) and 3 values (1.4%) within the acceptable zone B. Daytona
      showed 4 PG values <4.2 mmol/l (75 mg/dl) and their difference of respective
      Linus readings was always <0.83 mmol/l (15 mg/dl). Correlation of results was
      strong (r = 0.992). Glucometer Linus readings correspond to the ISO and FDA
      standards. So, Linus appears to be an accurate device for PG-self-monitoring and
      clinical practice.

PMID- 20694825
TI  - Conformational and thermodynamic characterization of the premolten globule state
      occurring during unfolding of the molten globule state of cytochrome c.
AB  - It has already been shown that the mutant Leu94Gly of horse cytochrome c exists
      in a molten globule (MG) state. We have carried out studies of reversible folding
      and unfolding induced by LiCl of this mutant at pH 6.0 and 25  degrees C by
      observing changes in the difference molar absorption coefficient at 402 nm, the
      mean residue ellipticity at 222 nm, and the difference mean residue ellipticity
      at 409 nm. This process is a three-state process when measured by these probes.
      The stable folding intermediate state has been characterized by far- and near-UV
      circular dichroism, tryptophan fluorescence, 8-anilino-1-naphthalenesulfonic acid
      binding, and dynamic light scattering measurements, which led us to conclude that
      the intermediate is a premolten globule (PMG). Analysis of the reversible
      unfolding transition curves for the stability of different states in terms of the
      Gibbs free energy change at pH 6.0 and 25  degrees C led us to conclude that the
      MG state is more stable than the PMG state by 5.4 +/- 0.1 kcal mol(-1), whereas
      the PMG state is more stable than the denatured (D) state by only 1.1 +/- 0.1
      kcal mol(-1). A comparison of the conformational and thermodynamic properties of
      the LiCl-induced PMG state at pH 6.0 with those of the PMG state induced by NaCl
      at pH 2.0 suggests that a similar PMG state is obtained under both denaturing
      conditions. Differential scanning calorimetry measurements suggest that heat
      induces a reversible two-state transition between MG and D states.

PMID- 20694826
TI  - Polysaccharides from Capsosiphon fulvescens stimulate the growth of IEC-6 Cells
      by activating the MAPK signaling pathway.
AB  - Seaweed extracts show diverse bioactivities, such as antioxidant and antitumor
      activity. Capsosiphon fulvescens is a green alga that is abundant along the
      southwest coast of South Korea. Although it is consumed for its purported health
      enhancing properties, particularly as a treatment for stomach disorders and
      hangovers, the health effects of dietary C. fulvescens remain unclear. We
      extracted polysaccharides from C. fulvescens (Cf-PS), investigated their effects
      on the proliferation of rat small intestinal epithelial IEC-6 cells, and
      determined the signaling cascade involved. We cultured IEC-6 cells in the
      presence of Cf-PS, which stimulated cell proliferation in a dose-dependent
      manner, and analyzed the Wnt and MAPK signaling pathways, which are related to
      cell proliferation. Cf-PS treatment induced the translocation of beta-catenin, an
      effector of the Wnt signaling pathway, from the cytosol to the nucleus and
      increased the expression of cyclinD1 and c-myc. Cf-PS also induced ERK1/2
      phosphorylation, which is activated by mitogenic and proliferative stimuli such
      as growth factors, but the phosphorylation of JNK and p38 was not enhanced. Our
      results show that Cf-PS regulates proliferation via stimulating the nuclear
      translocation of beta-catenin and ERK1/2 activation in intestinal epithelial
      cells.

PMID- 20694827
TI  - Vitreoscilla hemoglobin (VHb) overexpression increases hypoxia tolerance in
      zebrafish (Danio rerio).
AB  - Aquaculture farming may benefit from genetically engineering fish to tolerate
      environmental stress. Here, we used the vector pCVCG expressing the Vitreoscilla
      hemoglobin (vhb) gene driven by the common carp beta-actin promoter to create
      stable transgenic zebrafish. The survival rate of the 7-day-old F(2) transgenic
      fish was significantly greater than that of the sibling controls under 2.5% O(2)
      (dissolved oxygen (DO), 0.91 mg/l). Meanwhile, we investigated the relative
      expression levels of several marker genes (hypoxia-inducible factor alpha 1, heat
      shock cognate 70-kDa protein, erythropoietin, beta and alpha globin genes,
      lactate dehydrogenase, catalase, superoxide dismutase, and glutathione
      peroxidase) of transgenic fish and siblings after hypoxia exposure for 156 h. The
      expression profiles of the vhb transgenic zebrafish revealed that VHb could
      partially alleviate the hypoxia stress response to improve the survival rate of
      the fish. These results suggest that that vhb gene may be an efficient candidate
      for genetically modifying hypoxia tolerance in fish.

PMID- 20694829
TI  - Segregation of myoblast fusion and muscle-specific gene expression by distinct
      ligand-dependent inactivation of GSK-3beta.
AB  - Myogenic differentiation involves myoblast fusion and induction of muscle
      specific gene expression, which are both stimulated by pharmacological (LiCl),
      genetic, or IGF-I-mediated GSK-3beta inactivation. To assess whether stimulation
      of myogenic differentiation is common to ligand-mediated GSK-3beta inactivation,
      myoblast fusion and muscle-specific gene expression were investigated in response
      to Wnt-3a. Moreover, crosstalk between IGF-I/GSK-3beta/NFATc3 and Wnt/GSK
      3beta/beta-catenin signaling was assessed. While both Wnt-3a and LiCl promoted
      myoblast fusion, muscle-specific gene expression was increased by LiCl, but not
      by Wnt-3a or beta-catenin over-expression. Furthermore, LiCl and IGF-I, but not
      Wnt-3a, increased NFATc3 transcriptional activity. In contrast, beta-catenin
      dependent transcriptional activity was increased by Wnt-3a and LiCl, but not IGF
      I. These results for the first time reveal a segregated regulation of myoblast
      fusion and muscle-specific gene expression following stimulation of myogenic
      differentiation in response to distinct ligand-specific signaling routes of GSK
      3beta inactivation.

PMID- 20694831
TI  - Distribution and chemical partitioning of heavy metals in marine near-shore
      sediment cores: a case study from the Xugou, Lianyungang, China.
AB  - The concentrations and chemical partitioning of heavy metals (Co, Cr, Ni, Zn, Cu,
      and Pb) in the marine near-shore sediment cores were investigated. Typically, the
      mean concentrations from Core B sediment samples were 98.6, 21.1, 47.0, 46.4,
      107.6, and 31.9 mg kg( - 1) for Cr, Co, Ni, Cu, Zn, and Pb, respectively. The
      heavy metal concentrations were normalized to commonly used reference elements
      Al, Li, Sc, and total organic carbon. Based on Pearson coefficients, Li was found
      to be a good normalizer for Co (r = 0.974), Cr (r = 0.967), Ni (r = 0.898), and
      Zn (r = 0.929) in 80 sediment samples from three sampling sites. However, the
      correlation coefficients between Li and Cu, and Li and Pb were relatively low.
      Multivariate statistic approaches (Principal Component Analysis and Cluster
      Analysis) were adopted for data treatment, allowing the identification of two
      main factors controlling the heavy metal variability in the sediments. Heavy
      metals in the enrichment sections were evaluated by a sequential extraction
      method for possible chemical forms in sediments. The results showed that the
      residual, Fe/Mn oxides and Organic/sulfide fractions were dominant geochemical
      phases in the enriched sections, indicating low bioavailability of heavy metals
      in sediments.

PMID- 20694830
TI  - A new schedule of fotemustine in temozolomide-pretreated patients with relapsing
      glioblastoma.
AB  - In the present study we investigated the feasibility and effectiveness of a new
      biweekly schedule of fotemustine (FTM) in patients with recurrent glioblastoma,
      after at least one previous treatment. The primary endpoint was progression-free
      survival at 6 months; secondary objectives were clinical response, overall
      survival, disease-free survival, and toxicity. Forty patients (median age 52.8
      years; median Karnofsky Performance Status at progression 90) underwent second
      line chemotherapy with FTM. Selected patients were previously treated with a
      standard radiotherapy course with concomitant temozolomide (TMZ). After tumor
      relapse or progression proven by magnetic resonance imaging (MRI), all patients
      underwent chemotherapy with FTM, given intravenously at dose of 80 mg/m(2) every
      2 weeks for five consecutive administrations (induction phase), and then every 4
      weeks at 80 [DOSAGE ERROR CORRECTED] mg/m(2) as maintenance. A total of 329
      infusions were administered; the median number of cycles administered was 8. All
      patients completed the induction phase, and 29 patients received at least one
      maintenance infusion. Response to treatment was assessed using MacDonald
      criteria. One complete response [2.5%, 95% confidence interval (CI): 0-10%], 9
      partial responses (22.5%, 95% CI: 15-37%), and 16 stable diseases (40%, 95% CI:
      32-51%) were observed. Median time to progression was 6.7 months (95% CI: 3.9-9.1
      months). Progression-free survival at 6 months was 61%. Median survival from
      beginning of FTM chemotherapy was 11.1 months. The schedule was generally well
      tolerated; the main toxicities were hematologic (grade 3 thrombocytopenia in two
      cases). To the best of our knowledge, this is the first report specifically
      dealing with the use of a biweekly induction schedule of FTM. The study
      demonstrates that FTM has therapeutic efficacy as single-drug second-line
      chemotherapy with a favorable safety profile.

PMID- 20694832
TI  - Innate immunity and remodelling.
AB  - A wide variety of cardiac disease states can induce remodelling and lead to the
      functional consequence of heart failure. These complex disease states involve a
      plethora of parallel signal transduction events, which may be associated with
      tissue injury or tissue repair. Innate immunity is activated in hearts injured in
      different ways, evident as cytokine release from the heart, activation of toll
      like receptors involved in recognizing danger, and activation of the
      transcription factor nuclear factor kappa B. Nuclear factor kappa B regulates
      gene programmes involved in inflammation as well as the resolution of
      inflammation. The impact of this is an enigma; while cytokines, toll-like
      receptors, and nuclear factor kappa B appear to elicit myocardial protection in
      studies of preconditioning, the literature strongly indicates a detrimental role
      for activation of innate immunity in studies of acute ischaemia-reperfusion
      injury. The impact of activation of cardiac innate immunity on the long-term
      outcome in in vivo models of hypertrophy and remodelling is less clear, with
      conflicting results as to whether it is beneficial or detrimental. More research
      using genetically engineered mice as tools, different models of evoking
      remodelling, and long-term follow-up is required for us to conclude whether
      activation of the innate immune system is good, bad, or unimportant in chronic
      injury models.

PMID- 20694833
TI  - Restriction analysis and partial sequencing of the 16S rRNA gene as index for
      rapid identification of Bacillus species.
AB  - Restriction fragment length analysis of PCR amplified 16S rDNA with AluI revealed
      the presence of a 265 bp fragment in all species of Bacillus with the exception
      of B. cereus and B. thuringiensis, which contains two restriction sites within
      this fragment which results in three smaller fragments totalling to 265 bp. Some
      distant species of Bacillus with no evidence of this fragment could be delineated
      into other genera based on phenotypic and genotypic parameters. BLAST search for
      homologous sequences of individual species revealed that it is a highly conserved
      region. Multiple alignment of the fragment suggests that a region between 160 and
      265 bp of the 265 bp fragment was a hypervariable region and were highly species
      specific. A set of primers was designed for amplification of this hypervariable
      region. Partial sequencing of the hypervariable region within the 265 bp fragment
      seems an index for identification of Bacillus species.

PMID- 20694834
TI  - Seasonal patterns of the bacterioplankton community composition in a lake
      threatened by a pesticide disposal site.
AB  - BACKGROUND AIM AND SCOPE: The objective of the study was to determine the effects
      of ca. 35 years of pesticide contamination (pesticide dump-PD) of Lake Szelag
      Wielki (located in the north-eastern Poland) on changes in the microbial
      communities of aquatic ecosystems. In the years 2008-2009, analyses were carried
      out for seasonal changes in the quantity and composition of bacterioplankton in
      the lake examined, which is of high significance to the tourism and fishing
      industries and is located in the vicinity of an area subjected to reclamation
      after a pesticide dump. METHODS: Bacterioplankton composition was assayed by
      fluorescence in situ hybridisation technique for the contribution of major groups
      of the Bacteria domain: alpha-, beta- and gamma-Proteobacteria, Cytophaga
      Flavobacterium and Actinobacteria as well as bacteria capable of degrading
      pesticides in an aquatic environment-Pseudomonas spp. Seasonal patterns of the
      total number of bacteria were determined by direct counting of 4',6-diamidino-2
      phenylindole (DAPI)-stained cells. RESULTS: The percentage of the detected
      Eubacteria (EUB 338 probe) relative to all the DAPI-stained bacteria in Lake
      Szelag Wielki ranged from 46% to 63%. Bacteria capable of degrading pesticides in
      an aquatic environment-Pseudomonas spp.-were identified with a highly specific
      probe PEA 998. The highest mean values of this parameter reached 5.1%. In the
      spring, Pseudomonas spp. bacteria accounted for up to 80% of all Gamma
      Proteobacteria microbes. CONCLUSION: The study showed that the qualitative and
      quantitative changes in the bacterioplankton of the lake can be characterised by
      tendencies which are typical of a eutrophic water reservoir. However, a higher
      contribution of microorganisms capable of degrading sparingly degradable, toxic
      compounds and pesticides was determined in bacterioplankton from the PD
      contaminated lake, as compared to microbial communities of a lake not
      contaminated with pesticides.

PMID- 20694835
TI  - Seasonal atmospheric deposition variations of polychlorinated biphenyls (PCBs)
      and comparison of some deposition sampling techniques.
AB  - INTRODUCTION: Ambient air and bulk deposition samples were collected between June
      2008 and June 2009. Eighty-three polychlorinated biphenyl (PCB) congeners were
      targeted in the samples. DISCUSSION: The average gas and particle PCB
      concentrations were found as 393 +/- 278 and 70 +/- 102 pg/m(3), respectively,
      and 85% of the atmospheric PCBs were in the gas phase. Bulk deposition samples
      were collected by using a sampler made of stainless steel. The average PCB bulk
      deposition flux value was determined as 6,020 +/- 4,350 pg/m(2) day. The seasonal
      bulk deposition fluxes were not statistically different from each other, but the
      summer flux had higher values. Flux values differed depending on the
      precipitation levels. The average flux value in the rainy periods was 7,480 +/-
      4,080 pg/m(2) day while the average flux value in dry periods was 5,550 +/- 4,420
      pg/m(2) day. The obtained deposition values were lower than the reported values
      given for the urban and industrialized areas, yet close to the ones for the rural
      sites. The reported deposition values were also influenced by the type of the
      instruments used. The average dry deposition and total deposition velocity values
      calculated based on deposition and concentration values were found as 0.23 +/-
      0.21 and 0.13 +/- 0.13 cm/s, respectively.

PMID- 20694836
TI  - Adsorption of Pb, Cd, Cu, Zn, and Ni to titanium dioxide nanoparticles: effect of
      particle size, solid concentration, and exhaustion.
AB  - PURPOSE: Adsorption of metals (Pb, Cd, Cu, Ni, Zn) to TiO(2) nanoparticles and
      bulk particles was examined for use as a contaminant removal substrate as a
      function of particle size, sorbent concentration, and exhaustion. METHODS:
      Adsorption experiments were conducted with 0.01, 0.1, and 0.5 g/L nanoparticles
      in a pH 8 solution and in spiked San Antonio tap water. RESULTS: When results
      were normalized by mass, nanoparticles adsorbed more than the bulk particles but
      when results were surface-area normalized, the opposite was observed. The
      adsorption data shows the ability of the TiO(2) nanoparticles to remove Pb, Cd,
      and Ni from solution with similar adsorption at 0.1 and 0.5 g/L. Adsorption
      kinetics for all metals tested was described by a modified first order rate
      equation with the nanoparticles having a faster rate of adsorption than the bulk
      particles. The nanoparticles were able to simultaneously removal multiple metals
      (Zn, Cd, Pb, Ni, Cu) from both pH 8 solution and spiked San Antonio tap water.
      Exhaustion experiments showed that both the nanoparticles and bulk particles were
      exhausted at pH 6 but at pH 8, exhaustion did not occur for the nanoparticles.
      CONCLUSION: Comparison of K (d), distribution coefficient, with other literature
      showed that the nanoparticles were better sorbents than other metal oxide
      nanoparticles and a commercial activated carbon.

PMID- 20694837
TI  - Evolution of mycotic aortic aneurysm treatment by endovascular repair.
AB  - INTRODUCTION: Endovascular intervention for mycotic aortic aneurysms is now an
      alternative treatment option. CASE REPORT: An 83-year-old male presented with
      confusion and pyrexia of unknown origin. Acute deterioration and subsequent
      computed tomography scan of the abdomen revealed a contained rupture of a mycotic
      aortic aneurysm for which the patient had a successful endovascular repair.
      CONCLUSION: Endovascular management of aortic mycotic aneurysms provides an
      alternate and potentially safer method of intervention, particularly in patients
      deemed unsuitable for open repair.

PMID- 20694838
TI  - Vitamin D insufficiency: a common and treatable problem in the Irish population.
AB  - INTRODUCTION: Vitamin D insufficiency is an extremely common condition
      particularly in the older Irish population. This is a consequence of Ireland's
      geographical position and climate. A recent study showed more than 75% of a
      cohort of older Irish females had vitamin D insufficiency. OBJECTIVES: We outline
      the definition of vitamin D insufficiency and deficiency, its sources and
      metabolism as well as the clinical consequences of deficiency. We explore the
      current guidelines and discuss the pitfalls in the management of vitamin D
      replacement and in particular address recent Irish data on the feasibility and
      efficacy of intramuscular treatment. CONCLUSION: Vitamin D is important for
      calcium homeostasis and bone metabolism and reduced levels lead to osteomalacia,
      exacerbate osteoporosis and increase the risk of falls. Evidence is emerging that
      vitamin D has a role beyond musculoskeletal health and may impact on the
      cardiovascular and autoimmune systems, as well as the risk of malignancy.

PMID- 20694839
TI  - Features and management of colonic diverticular disease.
AB  - Diverticular disease is one of the most prevalent gastrointestinal conditions to
      afflict Western populations. Although the majority of patients with
      diverticulosis remain asymptomatic, about one third will develop symptoms at some
      point in their lives. Symptomatic diverticular disease can range from chronic
      mild gastrointestinal distress to acute bouts of diverticulitis complicated by
      abscess or frank colonic perforation. The mainstay of treatment of symptomatic
      diverticular disease has long been bowel rest, antibiotics, and pain control,
      reserving surgery for those with complicated disease. This review discusses the
      epidemiology, pathophysiology, clinical presentation, and management of the
      spectrum of diverticular disease, including recent advances in the treatment of
      chronic diverticular disease.

PMID- 20694840
TI  - Functional abdominal pain.
AB  - Functional abdominal pain syndrome (FAPS) is a relatively less common functional
      gastrointestinal (GI) disorder defined by the presence of constant or frequently
      recurring abdominal pain that is not associated with eating, change in bowel
      habits, or menstrual periods (Drossman Gastroenterology 130:1377-1390, 2006),
      which points to a more centrally targeted (spinal and supraspinal) basis for the
      symptoms. However, FAPS is frequently confused with irritable bowel syndrome and
      other functional GI disorders in which abdominal pain is associated with eating
      and bowel movements. FAPS also differs from chronic abdominal pain associated
      with entities such as chronic pancreatitis or chronic inflammatory bowel disease,
      in which the pain is associated with peripherally acting factors (eg, gut
      inflammation or injury). Given the central contribution to the pain experience,
      concomitant psychosocial disturbances are common and strongly influence the
      clinical expression of FAPS, which also by definition is associated with loss of
      daily functioning. These factors make it critical to use a biopsychosocial
      construct to understand and manage FAPS, because gut-directed treatments are
      usually not successful in managing this condition.

PMID- 20694841
TI  - Emerging pharmacologic therapies for irritable bowel syndrome.
AB  - New therapies are being developed for irritable bowel syndrome (IBS). These
      advances are based on understanding pathophysiology or the development of
      medications with greater selectivity in classes of agents with known efficacy.
      Prucalopride, the newest European Medicines Agency-approved 5-hydroxytryptamine
      receptor 4 (5-HT(4)) agonist, is effective in the treatment of chronic
      constipation with improved cardiovascular safety relative to older 5-HT(4) drugs;
      similarly, ramosetron, the 5-hydroxytryptamine receptor 3 (5-HT(3)) antagonist,
      appears efficacious in diarrhea-predominant IBS. Secretagogues with different
      mechanisms of action target apical domains in enterocytes that are involved in
      chloride secretion, such as chloride channels, the cystic fibrosis transmembrane
      regulator, and guanylate cyclase C. As a class, such secretagogues have high
      efficacy and safety for constipation. With more data obtained from phase 2 and 3
      trials, we expect other classes of medications, including bile acid modulators,
      anti-inflammatory agents, visceral analgesics, and newer centrally acting agents
      to be efficacious and enter the armamentarium for the treatment of IBS in the
      future.

PMID- 20694842
TI  - CD56 antigen expression and hemophagocytosis of leukemic cells in acute myeloid
      leukemia with t(16;21)(p11;q22).
AB  - The translocation t(16;21)(p11;q22) is rare, occurs with an incidence of 1%, in
      acute myeloid leukemia (AML), forming TLS/FUS-ERG fusion transcript, and it is
      known to cause the hemophagocytosis and vacuolation of leukemic cells. As
      previously reported cases numbered less than 60, we aimed to identify the
      clinical and genetic aspects of AML with t(16;21). Among 1,277 patients diagnosed
      with de novo and secondary AML, 12 AML patients with t(16;21) were
      retrospectively evaluated (0.94%, 12/1,277). AML with t(16;21) expressed CD56
      with a median value of 45% (7.8-87%), and the rate of hemophagocytosis plus
      vacuolation of leukemic cells was 2.9% (2.0-9.0%). CD56 antigen expression showed
      a correlation with the total rate of hemophagocytosis plus vacuolation, with a
      correlation coefficient of 0.663 (P = 0.019). AML with t(16;21) expressed CD13,
      CD33, CD34, CD117, CD56, HLA-DR, and cytoplasmic myeloperoxidase. RUNX1, which
      regulates a gene for hematopoiesis, is frequently mutated in AML and, in this
      study, one out of three patients showed the mutation R174Q in RUNX1. All of these
      3 patients showed the fusion transcript TLS/FUS-ERG, which was detected by
      multiplex or nested PCR. AML with t(16;21) showed a very low rate of complete
      remission after induction chemotherapy (8.3%), and high relapse (75%) and
      mortality (75%) rates. AML with t(16;21) exhibited a distinct morphology with
      frequent CD56 expression and a poor prognosis.

PMID- 20694843
TI  - Favorable outcomes of intravenous busulfan, fludarabine, and 400 cGy total body
      irradiation-based reduced-intensity conditioning allogeneic stem cell
      transplantation for acute myelogenous leukemia with old age and/or co
      morbidities.
AB  - Traditional transplant conditioning regimens have a limiting factor regarding co
      morbidities or old age. Therefore, reduced-intensity conditioning (RIC) regimens
      have been increasingly used. To define the role of RIC in AML with old age
      (>or=55 years) and/or co-morbidities (HCT-CI scores >or=2), we analyzed patients
      who received allogeneic stem cell transplantation (SCT) with Flu/Bu/TBI 400
      cGy/+/-antithymocyte globulin (ATG) conditioning regimen. Seventeen men and 15
      women were enrolled. The median age was 45 years (range 17-65 years). All
      patients were in first (n = 25) or second (n = 7) complete remission before
      undergoing allogeneic SCT. Patients were transplanted from HLA-mismatched
      unrelated donors (n = 5), matched unrelated donors (n = 10), and matched sibling
      (n = 17). Calcineurin inhibitor and a short course of standard dose methotrexate
      were used to prevent graft-versus-host disease (GVHD). All patients achieved
      engraftment. At a median follow-up of 18 months (range 4-40) for survivors, the
      estimated 2-year rates of overall survival, event-free survival, transplantation
      related mortality, and relapse were 66, 63, 26, and 16%, respectively. The
      incidence of acute (grades II-IV) and chronic GVHD by NIH consensus criteria was
      34.4 and 62.5%. This study suggests that the Flu/Bu/TBI 400 cGy or Flu/Bu/TBI 400
      cGy/ATG-based conditioning regimens maybe a feasible therapeutic approach for AML
      with old age and/or co-morbidities.

PMID- 20694845
TI  - Clinical features associated with REM sleep behavior disorder symptoms in the
      early stages of Parkinson's disease.
AB  - We aimed to characterize the clinical features associated with REM sleep
      behaviour disorder (RBD) in early stage Parkinson's disease (PD). Presence of
      clinical RBD was determined according to ICSD minimal clinical criteria and a
      validated RBD questionnaire. We registered time of appearance of RBD symptoms in
      relation to PD onset and the occurrence of RBD symptoms in the past in non-RBD
      patients. RBD and non-RBD groups were compared in terms of motor and cognitive
      dysfunction. The same comparisons were made between patients who reported RBD
      symptoms at some point in time (including those non-RBD patients that reported
      occurrence of RBD symptoms in the past) and those who did not (RBDS and non-RBDS,
      respectively). We assessed 75 patients. Forty-one (55%) patients presented with
      RBD, 19 beginning before PD onset. Five non-RBD patients reported having had RBD
      symptoms in the past. There were no significant differences between RBD and non
      RBD patients. RBDS group presented a significantly higher proportion of non
      tremor motor sub-type compared to non-RBDS patients. Our results suggest that RBD
      is very frequent in the early stages of PD. In some patients, RBD symptoms could
      have disappeared before or in the first years after motor disturbance onset. Non
      tremor motor sub-type was related to RBD symptoms history, rather than to the
      presence of RBD clinical criteria at time of evaluation, suggesting that the
      physiopathological changes that cause the association with motor status could
      remain, in spite of symptom fluctuation.

PMID- 20694844
TI  - Meta-analysis of heat- and chemically upregulated chaperone genes in plant and
      human cells.
AB  - Molecular chaperones are central to cellular protein homeostasis. In mammals,
      protein misfolding diseases and aging cause inflammation and progressive tissue
      loss, in correlation with the accumulation of toxic protein aggregates and the
      defective expression of chaperone genes. Bacteria and non-diseased, non-aged
      eukaryotic cells effectively respond to heat shock by inducing the accumulation
      of heat-shock proteins (HSPs), many of which molecular chaperones involved in
      protein homeostasis, in reducing stress damages and promoting cellular recovery
      and thermotolerance. We performed a meta-analysis of published microarray data
      and compared expression profiles of HSP genes from mammalian and plant cells in
      response to heat or isothermal treatments with drugs. The differences and
      overlaps between HSP and chaperone genes were analyzed, and expression patterns
      were clustered and organized in a network. HSPs and chaperones only partly
      overlapped. Heat-shock induced a subset of chaperones primarily targeted to the
      cytoplasm and organelles but not to the endoplasmic reticulum, which organized
      into a network with a central core of Hsp90s, Hsp70s, and sHSPs. Heat was best
      mimicked by isothermal treatments with Hsp90 inhibitors, whereas less toxic
      drugs, some of which non-steroidal anti-inflammatory drugs, weakly expressed
      different subsets of Hsp chaperones. This type of analysis may uncover new HSP
      inducing drugs to improve protein homeostasis in misfolding and aging diseases.

PMID- 20694846
TI  - Penetration of linezolid into rabbit intervertebral discs and surrounding
      tissues.
AB  - Linezolid belongs to a new class of synthetic antimicrobial agent that is
      effective for a variety of methicillin-resistant Staphylococcus aureus (MRSA)
      infections including bone and joint MRSA infections, but the effectiveness of
      linezolid for the treatment of MRSA spine infection remains controversial. In
      this study, we investigated the diffusion of linezolid or vancomycin into normal
      rabbit spinal tissues to determine the adequacy of linezolid for the treatment of
      spinal infection. The penetration efficacy of linezolid into the annulus
      fibrosus, nucleus pulposus, and vertebral bone (10, 8, and 10%, respectively) was
      lower than that of vancomycin (27, 11, and 14%, respectively). The penetration
      efficacy of linezolid into the bone marrow and iliopsoas muscle (88 and 84%,
      respectively), however, was higher than that of vancomycin (67 and 9%,
      respectively). These results suggest that linezolid is inadequate for the
      treatment of spine infection limited to the intervertebral disc, but may be
      effective for the treatment of infection extending into the muscle and bone
      marrow, such as in vertebral osteomyelitis, iliopsoas abscess, and postsurgical
      infection.

PMID- 20694847
TI  - Evaluation of ABM/P-15 versus autogenous bone in an ovine lumbar interbody fusion
      model.
AB  - A prospective, randomized study was performed in an ovine model to compare the
      efficacy of an anorganic bovine-derived hydroxyapatite matrix combined with a
      synthetic 15 amino acid residue (ABM/P-15) in facilitating lumbar interbody
      fusion when compared with autogenous bone harvested from the iliac crest. P-15 is
      a biomimetic to the cell-binding site of Type-I collagen for bone-forming cells.
      When combined with ABM, it creates the necessary scaffold to initiate cell
      invasion, binding, and subsequent osteogenesis. In this study, six adult ewes
      underwent anterior-lateral interbody fusion at L3/L4 and L4/L5 using PEEK
      interbody rings filled with autogenous bone at one level and ABM/P-15 at the
      other level and no additional instrumentation. Clinical CT scans were obtained at
      3 and 6 months; micro-CT scans and histomorphometry analyses were performed after
      euthanization at 6 months. Clinical CT scan analysis showed that all autograft
      and ABM/P-15 treated levels had radiographically fused outside of the rings at
      the 3-month study time point. Although the clinical CT scans of the autograft
      treatment group showed significantly better fusion within the PEEK rings than
      ABM/P-15 at 3 months, micro-CT scans, clinical CT scans, and histomorphometric
      analyses showed there were no statistical differences between the two treatment
      groups at 6 months. Thus, ABM/P-15 was as successful as autogenous bone graft in
      producing lumbar spinal fusion in an ovine model, and it should be further
      evaluated in clinical studies.

PMID- 20694848
TI  - Outcome of thoracolumbar burst fractures treated with indirect reduction and
      fixation without fusion.
AB  - Indirect reduction and fixation is not a new method in the treatment of
      thoracolumbar burst fractures but the indications and efficacy are controversial.
      The current study was designed to evaluate the efficacy of indirect reduction
      without fusion. Sixty-four patients with single-level thoracolumbar burst
      fractures were identified and treated by this method. The outcome was analyzed by
      the Frankel method, radiographic measurements, and at the latest follow-up the
      Denis Pain Scale and Oswestry disability index (ODI) were used to assess back
      pain and functional outcome. The average follow-up period was 40.1 months. The
      anterior vertebral height (AVH) was corrected from 55.2 to 97.2% post-operatively
      and decreased to 88.9% after hardware removal. The posterior vertebral height
      (PVH) increased from 88.9 to 99.1% post-operatively and decreased slightly after
      implant removal to 93.7%. The average pre-operative canal compromise was 41.4%,
      which decreased to 13.7% at last follow-up. Except for three paraplegic patients,
      neurological status significantly improved or stayed normal in the study's
      remaining 61 patients. Fifty-two of sixty-four patients had excellent or good
      function. At latest follow-up the average ODI score was 16.7 and the Denis pain
      score improved in all patients but one. Indirect reduction and fixation can not
      only restore vertebral column structure but also, more importantly, patients'
      functional outcome.

PMID- 20694849
TI  - Thoracoscopic assisted en bloc resection of a spine tumor.
AB  - Spine tumors are fairly common and the management is through a multimodality
      approach. Lesions of the thoracic and lumbar vertebrae have been treated with
      such extensive anterior and/or posterior approaches. The authors present a case
      of a 56-year-old lady with solitary T11 metastases from colonic carcinoma and a
      case of a 43-year-old lady with T5-T6 high-grade osteogenic sarcoma. The
      treatment consists of a wide vertebrectomy by posterior approach, after anterior
      release and sub-pleural dissection using a thoracoscopic approach. A
      thoracoscopic assisted anterior approach could reduce the duration and the
      morbidity of a vertebrectomy without affecting oncological management.

PMID- 20694850
TI  - Prosthetic incisional hernioplasty: clinical experience with 354 cases.
AB  - BACKGROUND: The use of prosthetic materials has become the standard of care in
      the management of incisional hernias because of its association with a low rate
      of recurrence. In this paper, the results of the treatment of incisional hernias
      is reported. METHODS: Over a 15-year period, 354 open abdominal wall incisional
      hernia repairs were performed using the Rives-Stoppa, onlay and inlay techniques.
      The prosthetic materials used were polypropylene and Mersilene mesh. Using a
      questionnaire, the individual characteristics, type of operation (technique),
      type of prosthesis, complications and surgical outcome were recorded and analysed
      by SPSS software. RESULTS: A total of 354 patients underwent prosthetic
      incisional hernioplasty, comprising 265 women and 89 men, with a mean age of 52.1
      years, using three techniques that included Rives-Stoppa (312), onlay (33) and
      underlay (9). The majority of complications included seroma (10), infection (8),
      intestinal fistula (2), mesh removal (2) and respiratory complication (4). Eighty
      percent of the patients used abdominal belts after the surgical procedure.
      Recurrent hernias were observed in four patients with a mean of 98 months follow
      up. All patients received pre-operative intravenous antibiotics and were
      discharged with oral antibiotics. CONCLUSION: In this series, the prosthetic
      incisional hernioplasty approaches, especially the Rives-Stoppa method, yielded
      excellent long-term results, with minimal morbidity in patients and large primary
      or recurrent incisional repair.

PMID- 20694851
TI  - Increasing Pleurotus ostreatus laccase production by culture medium optimization
      and copper/lignin synergistic induction.
AB  - Laccases have great biotechnological potential in diverse industries as they
      catalyze the oxidation of a broad variety of chemical compounds. Production of
      laccases by basidiomycetes has been broadly studied as they secrete the enzymes,
      grow on cheap substrates, and they generally produce more than one isoenzyme
      (constitutive and/or inducible). Laccase production and isoenzyme profile can be
      modified through medium composition and the use of inducers. The objective of
      this work was to increase laccase production by Pleurotus ostreatus CP-50 through
      culture medium optimization and the simultaneous use of copper and lignin as
      inducers. Increased fungal growth was obtained through the use of a factorial
      fractional experimental design 26-2 where the influence of the nature and
      concentration of carbon and nitrogen sources was assessed. Although specific
      laccase production (U/mg biomass) decreased when malt extract medium was
      supplemented with carbon and nitrogen sources, fungal growth and laccase
      volumetric activity increased four and sixfold, respectively. The effect of media
      supplementation with copper and/or lignin on laccase production by P. ostreatus
      CP-50 was studied. A positive synergistic effect between copper and lignin was
      observed on laccase production. Overall, the use of an optimized medium and the
      simultaneous addition of copper and lignin improved growth, laccase volumetric
      activity, and process productivity by 4-, 60-, and 10-fold, respectively.

PMID- 20694852
TI  - L: (+)-Lactic acid production from non-food carbohydrates by thermotolerant
      Bacillus coagulans.
AB  - Lactic acid is used as an additive in foods, pharmaceuticals, and cosmetics, and
      is also an industrial chemical. Optically pure lactic acid is increasingly used
      as a renewable bio-based product to replace petroleum-based plastics. However,
      current production of lactic acid depends on carbohydrate feedstocks that have
      alternate uses as foods. The use of non-food feedstocks by current commercial
      biocatalysts is limited by inefficient pathways for pentose utilization. B.
      coagulans strain 36D1 is a thermotolerant bacterium that can grow and efficiently
      ferment pentoses using the pentose-phosphate pathway and all other sugar
      constituents of lignocellulosic biomass at 50 degrees C and pH 5.0, conditions
      that also favor simultaneous enzymatic saccharification and fermentation (SSF) of
      cellulose. Using this bacterial biocatalyst, high levels (150-180 g l(-1)) of
      lactic acid were produced from xylose and glucose with minimal by-products in
      mineral salts medium. In a fed-batch SSF of crystalline cellulose with fungal
      enzymes and B. coagulans, lactic acid titer was 80 g l(-1) and the yield was
      close to 80%. These results demonstrate that B. coagulans can effectively ferment
      non-food carbohydrates from lignocellulose to L: (+)-lactic acid at sufficient
      concentrations for commercial application. The high temperature fermentation of
      pentoses and hexoses to lactic acid by B. coagulans has these additional
      advantages: reduction in cellulase loading in SSF of cellulose with a decrease in
      enzyme cost in the process and a reduction in contamination of large-scale
      fermentations.

PMID- 20694853
TI  - Effect of trace metals on ethanol production from synthesis gas by the
      ethanologenic acetogen, Clostridium ragsdalei.
AB  - The effect of trace metal ions (Co2+, Cu2+, Fe2+, Mn2+, Mo6+, Ni2+, Zn2+, SeO4-
      and WO4-) on growth and ethanol production by an ethanologenic acetogen,
      Clostridium ragsdalei was investigated in CO:CO2-grown cells. A standard acetogen
      medium (ATCC medium no. 1754) was manipulated by varying the concentrations of
      trace metals in the media. Increasing the individual concentrations of Ni2+,
      Zn2+, SeO4- and WO4- from 0.84, 6.96, 1.06, and 0.68 MUM in the standard trace
      metals solution to 8.4, 34.8, 5.3, and 6.8 MUM, respectively, increased ethanol
      production from 35.73 mM under standard metals concentration to 176.5, 187.8,
      54.4, and 72.3 mM, respectively. Nickel was necessary for growth of C. ragsdalei.
      Growth rate (MU) of C. ragsdalei improved from 0.34 to 0.49 (day-1), and carbon
      monoxide dehydrogenase (CODH) and hydrogenase (H2ase)-specific activities
      improved from 38.45 and 0.35 to 48.5 and 1.66 U/mg protein, respectively, at
      optimum concentration of Ni2+. At optimum concentrations of WO4- and SeO4-,
      formate dehydrogenase (FDH) activity improved from 32.3 to 42.6 and 45.4 U/mg
      protein, respectively. Ethanol production and the activity of FDH reduced from 35
      mM and 32.3 U/mg protein to 1.14 mM and 8.79 U/mg protein, respectively, upon
      elimination of WO4- from the medium. Although increased concentration of Zn2+
      enhanced growth and ethanol production, the activities of CODH, FDH, H2ase and
      alcohol dehydrogenase (ADH) were not affected by varying the Zn2+ concentration.
      Omitting Fe2+ from the medium decreased ethanol production from 35.7 to 6.30 mM
      and decreased activities of CODH, FDH, H2ase and ADH from 38.5, 32.3, 0.35, and
      0.68 U/mg protein to 9.07, 7.01, 0.10, and 0.24 U/mg protein, respectively.
      Ethanol production improved from 35 to 54 mM when Cu2+ was removed from the
      medium. The optimization of trace metals concentration in the fermentation medium
      improved enzyme activities (CODH, FDH, and H2ase), growth and ethanol production
      by C. ragsdalei.

PMID- 20694854
TI  - Lovastatin induces neuronal differentiation and apoptosis of embryonal carcinoma
      and neuroblastoma cells: enhanced differentiation and apoptosis in combination
      with dbcAMP.
AB  - Differentiation-based therapeutics are an underutilized but a potentially
      significant treatment option for cancer patients. We show that lovastatin, a
      competitive inhibitor of the rate-limiting enzyme of mevalonate synthesis HMG-CoA
      reductase, is able to induce tumour cell differentiation and apoptosis in vitro.
      We used embryonal carcinoma (EC) and neuroblastoma (NB) cell lines and found that
      lovastatin promoted apoptosis and induced expression of the neuronal
      differentiation markers, tyrosine hydroxylase (TH), and growth-associated protein
      43. The apoptotic and differentiation responses were time and dose-dependant and
      rescued by the co-administration of mevalonate. The expression of TH is regulated
      primarily by a cyclic AMP (cAMP) response element (CRE) in its promoter.
      Lovastatin enhanced the expression of a CRE-driven luciferase construct in P19
      cells. Furthermore, combining lovastatin with 1 mM dibutyryladenosine 3',5'
      cyclic monophosphate treatments induced higher expression from the CRE construct,
      enhanced differentiation and cytotoxicity. This study suggests the potential of
      combining these therapeutic approaches in EC and NB patients.

PMID- 20694855
TI  - Identification and characterization of toxigenic fusaria associated with sorghum
      grain mold complex in India.
AB  - Fusarium species are dominant within the sorghum grain mold complex. Some species
      of Fusarium involved in grain mold complex produce mycotoxins, such as
      fumonisins. An attempt was made to identify Fusarium spp. associated with grain
      mold complex in major sorghum-growing areas in India through AFLP-based grouping
      of the isolates and to further confirm the species by sequencing part of alpha
      Elongation factor gene and comparing the sequences with that available in the
      NCBI database. The dendrogram generated from the AFLP data clustered the isolates
      into 5 groups. Five species of Fusarium--F. proliferatum, F. thapsinum, F.
      equiseti, F. andiyazi and F. sacchari were identified based on sequence
      similarity of alpha-Elongation factor gene of the test isolates with those in the
      NCBI database. Fusarium thapsinum was identified as predominant species in
      Fusarium--grain mold complex in India and F. proliferatum as highly toxigenic for
      fumonisins production. Analysis of molecular variance (AMOVA) revealed 54% of the
      variation in the AFLP patterns of 63 isolates was due to the differences between
      Fusarium species, and 46% was due to differences between the strains within a
      species.

PMID- 20694856
TI  - Validity and reliability of the Philadelphia Geriatric Center Morale Scale among
      Turkish elderly people.
AB  - PURPOSE: We translated the original 17-item Philadelphia Geriatric Morale Scale
      (PGCMS) into Turkish and examined its validity and reliability to determine
      whether it may used as a tool to measure quality of life (QOL) in a Turkish
      elderly sample people. METHODS: The sample included 398 participants aged 65
      years living in institutions. Participants who were cognitively impaired
      (Abbreviated Mental Test score less than 7) or who could not answer questions for
      other reasons were excluded. Preliminary analysis was conducted to investigate
      multicollinearity, univariate and multivariate outliers, normality, item
      difficulty and discriminatory power of individual items. Confirmatory factor
      analysis (CFA) was used to test the structure of the PGCMS. By means of
      convergent-divergent validity, correlations between PGCMS and Turkish SF-36,
      correlations between PGCMS and social support scores, and correlations between
      PGCMS and hopelessness scores were investigated. Reliability was based on
      internal consistency investigated by Kuder-Richardson-20 (KD-20) and item-total
      correlation. RESULTS: By means of multicollinearity, we deleted two items.
      Neither univariate nor multivariate outliers were found. No items showed skewness
      and kurtosis value greater than recommended. A model containing 15 of the PGCMS
      items was found to fit Turkish data perfectly. We identified three underlying
      factors including agitation, attitude toward own aging, and lonely
      dissatisfaction similar to original PGCMS's three-factor solution. There were
      strong correlations between PGCMS's subscales. The correlations with the physical
      and mental domain in SF-36, correlations between PGCMS and social support, and
      correlation between PGCMS and hopelessness supported construct validity. We found
      satisfactory evidence of internal consistency (KD-20 was 0.92 for total PGCMS and
      it ranged from 0.76 to 0.85 for subscales in the PGCMS) with item-total
      correlations ranging from 0.39 to 0.73. CONCLUSIONS: The PGCMS is a valid and
      reliable quality of life measure in elderly Turkish people.

PMID- 20694857
TI  - New model to explain the EQ-5D VAS in patients who have undergone spinal fusion.
AB  - BACKGROUND: In the health sector, the EQ-5D has been widely used to evaluate
      health-related quality of life, mainly due to its simplicity, robustness and
      plasticity in calculating years of life adjusted for quality. METHODS: However,
      its model has remained stable over time and knowledge of the influence of such
      biodemographical variables as age and gender has not been incorporated. This
      information, along with the well-known non-linear behavior of the VAS, which
      measures the self-concept of the 'General State of Health', forms the basis for a
      new model, which we present here from a sample of patients who were operated on
      for chronic low back pain. RESULTS: These are obtained using multiple regression
      analysis are consistent in terms of goodness-of-fit given that this new model is
      able to explain 91.3% of the self-concept of the 'general state of health'.
      CONCLUSIONS: Above leads to an improvement of 21.6% compared to the available
      models more robust and meets most of the restrictions for this type of
      statistical modeling.

PMID- 20694858
TI  - Masked hypertension: evidence of the need to treat.
AB  - The diagnosis of masked hypertension has been made easier with the widespread
      availability of home blood pressure monitoring devices with levels of accuracy
      comparable to ambulatory blood pressure monitoring. The negative impact of masked
      hypertension on cardiovascular morbidity and mortality is evidenced by numerous
      well-designed clinic-based and population-based studies. The relationship of
      masked hypertension and target organ damage is also well documented. These two
      factors, combined with the robust evidence of reduced cardiovascular morbidity
      and mortality achieved with blood pressure treatment, makes the argument for
      actively identifying patients with masked hypertension and prescribing treatment
      similar to that for patients with sustained hypertension. In this paper, we
      review the evidence for the cardiovascular prognosis of masked hypertension
      compared with sustained hypertension, we review its impact on target organ
      damage, we propose an algorithm for the treatment of patients with masked
      hypertension, and we point out the pitfalls in adopting such an approach.

PMID- 20694860
TI  - The impact of experienced emotion on evaluative judgments: the effects of age and
      emotion regulation style.
AB  - Adults aged from 24 to 79 were exposed to four commercial advertisements within
      the context of television programs designed to induce either a positive or
      negative mood. Although age was associated with memory for the content of the
      commercials, it did not moderate the impact of mood on evaluations of the
      advertised products. Instead, participants who reported engaging in expressive
      suppression as a common emotion regulation strategy were more likely to make
      evaluations that were biased by moods than those individuals who reported low use
      of this strategy. The results suggest that the maintenance of emotion regulation
      ability in later adulthood may help people control certain affective influences
      on thought.

PMID- 20694861
TI  - Dissociative and metacognitive factors in hallucination-proneness when
      controlling for comorbid symptoms.
AB  - INTRODUCTION: Recent studies have linked hallucination-proneness to dysfunctional
      metacognitive beliefs, dissociation, and disrupted capacity to discriminate
      between internal and external cognitive events (reality discrimination). This
      study addressed a number of methodological limitations of previous research by
      investigating the relationship between hallucination-proneness and the
      aforementioned variables while controlling for comorbid symptoms. METHOD: A large
      sample of nonclinical participants was screened on measures of hallucination
      proneness, cognitive intrusions, paranoid ideation, metacognitive beliefs, and
      dispositional mindfulness (including measures of dissociation-like experiences).
      In addition, a signal detection task was used to investigate reality
      discrimination in four subgroups of participants selected on the basis of their
      scores on hallucination-proneness and intrusions. RESULTS: Regression analyses
      for the self-report data were conducted to investigate the predictors of
      hallucination-proneness and paranoia when controlling for comorbid symptoms.
      Also, between-group differences on the behavioural data were tested to determine
      whether perturbed reality discrimination is specifically associated with
      hallucination-proneness rather than cognitive intrusions. Results revealed that
      metacognitive beliefs are more strongly associated with intrusions and paranoia
      than hallucination-proneness, whereas hallucination-proneness is related to
      perturbed reality discrimination and dissociation. CONCLUSIONS: These results
      clarify previous research on metacognitive dysfunction in hallucination
      proneness, and highlight the importance of controlling for the covariation among
      symptoms when investigating the cognitive processes underlying psychotic
      experiences.

PMID- 20694862
TI  - A new intelligent approach for estimation of blood potassium concentration.
AB  - This paper introduces a new approach for estimation of blood potassium
      concentration. This approach is based on a neurofuzzy inference system that
      combines the attributes of both fuzzy logic and neural networks. This approach
      has many attractive clinical features. First, it represents a computerised
      intelligent method for accurately estimating blood potassium without the need for
      a potassium sensor. Second, it helps the clinicians in diagnosis and treatment of
      potassium disorders and also reduces the time required to deal with them. Third,
      it enhances the patient's comfort and compliance due to a significant reduction
      in blood sample volume required to conduct the electrolytes analysis. Lastly, the
      developed approach explains the complex physiological homeostasis of blood
      electrolytes which is very important for the design of decision-making systems
      for medical applications. Furthermore, the validation results of this method
      showed that it is capable of estimating the blood potassium with an accuracy
      satisfying clinical standards.

PMID- 20694863
TI  - Effects of sitting postures on risks for deep tissue injury in the residuum of a
      transtibial prosthetic-user: a biomechanical case study.
AB  - Transtibial amputation prosthetic-users are at risk of developing deep tissue
      injury (DTI) while donning their prosthesis for prolonged periods; however, no
      study addresses the mechanical loading of the residuum during sitting with a
      prosthesis. We combined MRI-based 3D finite element modelling of a residuum with
      an injury threshold and a muscle damage law to study risks for DTI in one sitting
      subject in two postures: 30 degrees -knee-flexion vs. 90 degrees -knee-flexion.
      We recorded skin-socket pressures, used as model boundary conditions. During the
      90 degrees -knee-flexion simulations, major internal muscle injuries were
      predicted (>1000 mm(3)). In contrast, the 30 degrees -knee-flexion simulations
      only produced minor injury ( < 14 mm(3)). Predicted injury rates at 90 degrees 
      knee-flexion were over one order of magnitude higher than those at 30 degrees 
      knee-flexion. We concluded that in this particular subject, prolonged 90 degrees 
      knee-flexion sitting theoretically endangers muscle viability in the residuum. By
      expanding the studies to large subject groups, this research approach can support
      development of guidelines for DTI prevention in prosthetic-users.

PMID- 20694864
TI  - Validation of the Boussinesq equation for use in traction field determination.
AB  - Cell traction force plays an important role in many biological processes. Several
      traction force microscopy methods have been developed to determine cell traction
      forces based on the Boussinesq solution. This approach, however, is rooted in a
      half-space assumption. The purpose of this study was to determine the error
      induced in the half-space assumption using a finite element method (FEM). It
      demonstrates that displacement error between the FEM and the Boussinesq equation
      can be used to measure the accuracy of the Boussinesq equation, although
      singularity exists in the loading point. For one concentrated force, significant
      difference between the FEM and the Boussinesq equation occurs in the whole field;
      this difference decreases with an increase in the plate thickness. However, in
      the case of the balanced forces, the offset of the balanced forces decreases the
      errors in the middle area. Overall, this study demonstrates that increasing the
      thickness of the polyacrylamide gel is important for reducing the error of the
      Boussinesq equation when determining the displacement field of the gel under
      loads.

PMID- 20694865
TI  - Exploring health beliefs and care-seeking behaviors of older USA-dwelling
      Mexicans and Mexican-Americans.
AB  - OBJECTIVE: This study explored health beliefs and healthcare-seeking behaviors of
      older USA-dwelling Mexicans and Mexican-Americans using the Theory of Planned
      Behavior (TPB) as a conceptual guide. DESIGN: A mixed-method cross-sectional
      design was utilized using semi-structured interviews to obtain detailed
      descriptions of 31 older (50+) participants' behavioral, normative, and control
      beliefs about health and healthcare utilization. An interview schedule consisting
      of open-ended and demographic questions and one standardized tool, the
      Bidimensional Acculturation Scale (BAS) for Hispanics, was used to collect data.
      RESULTS: Several themes emerged for each belief area. Behavioral belief themes
      reflect participants' faith in, comfort with, and knowledge of traditional
      methods of care (e.g., herbs, teas, and use of curanderas) as well as their faith
      in the effectiveness of conventional care (e.g., medicine, technology, and use of
      physicians). Normative belief themes indicate that participants perceive that
      family and community contacts support participants' use of traditional methods
      and that family supports use of conventional methods. Control belief themes
      suggest that traditional methods are accessible and affordable but that
      conventional methods are not. BAS scored indicated that most (90.3%) participants
      adhered to Hispanic culture. Two (6.5%) participants adhered to non-Hispanic
      culture and one (3.2%) scored as bi-cultural. CONCLUSIONS: Themes from the data
      suggest that beliefs about healthcare impact the types of care utilized and the
      ways in which they are utilized. Clinicians and researchers striving to reduce
      health disparities and develop more culturally competent healthcare services for
      ethnic minority groups should work toward a better understanding of minority
      groups' belief systems about healthcare and its utilization. Utilization of the
      TPB allows for empirical model development that can better predict healthcare
      utilization behavior, further augmenting efforts to provide services that will
      help reduce health disparities for older Mexicans and Mexican-Americans and other
      populations.

PMID- 20694866
TI  - How Iranian lay people in three ethnic groups conceptualize a case of a depressed
      woman: an explanatory model.
AB  - OBJECTIVE(S): Although depression is a major public health problem, little is
      known about lay people's views of this subject in Iran. The aim of this study was
      to explore how depression in women is viewed among lay people in three major
      ethnic groups--Kurd, Turk, and Fars. DESIGN: Participants were selected from
      public urban healthcare centers. Four focus group discussions were conducted for
      each of the three ethnic groups and classified by level of education from three
      locations, in the capital city (Tehran), west (Ilam), and the northwest (Tabriz)
      of Iran. Twelve focus groups; 38 men and 38 women have been conducted by using a
      case vignette describing a woman with major depression. RESULTS: Depression
      symptoms were perceived as a temporary phenomenon. It was regarded as a
      colloquial term for feeling blue, mostly related to external stressors (social
      model). The common terms used in all ethnic groups were depression, and
      nerve/soul distress. Environmental cause and war were considered as external
      causes of the symptoms, and emotional factors, cognition distortion, and
      biological reasons, as internal factors. The participants believed it was
      necessary to seek help from religion, family and friends, positive thinking, and
      distraction from social problems, besides consultations with psychologists as
      counselors. Medication was often seen as the last resort. Stigma was mentioned as
      an important factor that makes people avoid visiting psychiatrists. CONCLUSION:
      These data may have implications for mental healthcare practice, especially for
      the approach to diagnosis of depression. Moreover, there is a need for developing
      and integrating gender-relevant and cultural indicators in the existing national
      mental health systems in Iran.

PMID- 20694867
TI  - Ethnic notions and healthy paranoias: understanding of the context of experience
      and interpretations of healthcare encounters among older Black women.
AB  - OBJECTIVES: To report the first-hand perspectives of older Black women within
      healthcare encounters that impact the trajectories of health-seeking behavior; to
      examine their perceptions, expectations, and beliefs about the role of cultural
      difference within predominantly White (US) healthcare settings; and to explore
      how sharing personal experiences (theirs and others') as a fund of knowledge
      influences ethnic notions. This research is aimed at the development of community
      resource partnerships and effective healthcare service delivery with intervention
      and promotion efforts targeting older Black women. DESIGN: Ethnographic data
      collected over a 24-month period (2003-2005) from 50 older Black women in Tucson,
      AZ, USA are discussed on three levels: (1) expectations and beliefs; (2) the use
      of ethnic notions in the form of healthy paranoias as part of individual and
      communal health advocacy; and (3) perceptions of interethnic communication within
      healthcare settings, including feeling uncared for by healthcare providers and
      support staff. RESULTS: Disparities in older Black women's health and well-being
      are often constructed and filtered through 'non-clinical' influences, such as
      cultural differences, individual experiences, and beliefs about 'race' or 'being'
      a Black female. CONCLUSIONS: Unfamiliarity with ethnic notions may cause
      misinterpretations and misunderstandings and may influence interactions between
      older Black women and healthcare providers.

PMID- 20694868
TI  - Suicidal behavior and ethnicity of young females in Rotterdam, The Netherlands:
      rates and risk factors.
AB  - OBJECTIVE: Although Western Europe is becoming increasingly multicultural, ethnic
      minorities are scarcely included in studies of suicidology. We investigated the
      prevalence of non-fatal suicidal behavior and examined risk factors in non
      western female immigrant adolescents compared to majority female adolescents in
      the city of Rotterdam, The Netherlands. DESIGN: We conducted logistic regression
      on a dataset that consisted of self-reported health and well-being questionnaires
      filled out by 4527 adolescents of Dutch, South Asian-Surinamese, Moroccan, and
      Turkish origin. We examined whether young females of specific ethnic groups had
      elevated risk for attempted suicide. Well-known risk factors in suicidology of
      social economic class, level of education, life events, abuse, and family context
      were investigated to verify whether these factors are beneficial to explaining
      ethnic differences in suicidal behavior. RESULTS; We found that rates of
      attempted suicide among Turkish and South Asian-Surinamese young women were
      higher than of Dutch females, while Moroccan females had lower rates than Dutch
      female adolescents. Physical and sexual abuse, and an impaired family
      environment, as well as parental psychopathology or parental substance abuse
      contributed to non-fatal suicidal behavior of females across ethnicities.
      However, these risk factors, as well as low social economic class and of level of
      education, did not fully explain the vulnerability of Turkish and South Asian
      Surinamese females. CONCLUSION: Our findings underscored the need for developing
      suicide prevention for specific minority females in multicultural cities in
      Western Europe. Screening programs, which aim at preventing suicide attempts by
      young immigrant women should include risk factors in the family environment and
      relationship with the parents as well as physical and sexual abuse. However, the
      study also showed that the disproportionate risk of Turkish and South Asian
      Surinamese females could not be understood by risk factors alone and transpired
      that the origins of ethnic disparities in suicidal behavior deserve further
      examination.

PMID- 20694869
TI  - Lifetime, low-dose ochratoxin A dietary study on renal carcinogenesis in male
      Fischer rats.
AB  - Carcinoma arising from male rat renal parenchyma is an aspect of the
      nephrotoxicity of ochratoxin A (OTA) and is a factor in considering application
      of animal data to human health risk assessment. We present experimental data to
      complement already published and to complete dose-response findings for dietary
      OTA. From 34 rats, only four unilateral renal carcinomas (12%) developed during a
      2-year exposure to dietary OTA, contaminated to give the same weekly overall
      dosage as in the 50 ug kg(-1) gavage-dosing regimen of an NTP study (30%).
      Statistical analysis included adjustment for premature leukaemia deaths,
      resulting in the carcinoma incidence of 35% (10-81%), and showed no significant
      difference from NTP (incidence of 43% (23-49%)) due to the smaller number of
      animals. However, absence of microscopic neoplastic renal lesions in premature
      decedents argues for minimal effect of the 47% leukaemia on carcinoma expression
      in the present experiment. This would fit with previously published findings
      showing significantly less carcinoma expression from a regimen administering an
      OTA dose in feed than was achieved by a lower dose by gavage as in the NTP study.
      It is concluded that chronic gavage administration of OTA to male rats may
      optimise carcinoma incidence for toxicological purposes, but that the dietary
      mode gives data more applicable to assessing putative health risk for humans.

PMID- 20694870
TI  - HIV+ men and women show different performance patterns on procedural learning
      tasks.
AB  - The literature suggests that nondeclarative, or nonconscious, learning might be
      impaired among HIV-seropositive (HIV+) individuals compared with HIV-seronegative
      (HIV-) matched control groups, but these studies have included relatively few
      women. We administered measures of motor skill and probabilistic learning, tasks
      with a nondeclarative or procedural learning component that are dependent on
      integrity of prefrontal-striatal systems, to well-matched groups of 148 men and
      65 women with a history of substance dependence that included 45 men and 30 women
      seropositive for HIV. All participants were abstinent at testing. Compared to HIV
      women, HIV+ women performed significantly more poorly on both tasks, but HIV+
      men's performance did not differ significantly from that of HIV- men on either
      task. These different patterns of performance indicate that features of HIV
      associated neurocognitive disorder (HAND) cannot always be generalized from men
      to women. Additional studies are needed to address directly the possibility of
      sex differences in HAND and the possibility that women might be more vulnerable
      to the effects of HIV and substance dependence on some neurocognitive functions.

PMID- 20694871
TI  - Attentional set shifting in autism spectrum disorder: differentiating between the
      role of perseveration, learned irrelevance, and novelty processing.
AB  - Autism spectrum disorders (ASD) are associated with impaired attentional set
      shifting, which may reflect enhanced perseverative responding, enhanced learned
      irrelevance, and/or reduced novelty processing. We assessed the contribution of
      these potential error sources in ASD adults. A total of 17 ASD and 19 matched
      comparison individuals first solved a discrimination learning task. Thereafter,
      the participants faced three types of attentional shift, specifically designed to
      isolate the effect of the three possible error sources. ASD participants made
      more errors than comparison individuals in a shift implying a choice between a
      novel relevant stimulus attribute and a familiar attribute that was previously
      relevant but now irrelevant. However, they made fewer errors in a shift involving
      a choice between a novel irrelevant attribute and a familiar, previously
      irrelevant but now relevant attribute. The results in combination suggest that
      the performance difference, at least in the present shift task, is caused by
      reduced novelty processing in ASD participants.

PMID- 20694872
TI  - Discounting of delayed rewards and executive dysfunction in individuals infected
      with hepatitis C.
AB  - OBJECTIVE: Determine whether adults with hepatitis C (HCV), regardless of
      substance use disorder, are more likely to discount delayed rewards than adults
      without hepatitis C, and explore the relationship between delay discounting and
      neuropsychological functioning. METHODS: Procedures included clinical interviews,
      neuropsychological testing, and a delay discounting task. RESULTS: Regardless of
      substance abuse history, adults with hepatitis C were significantly more likely
      to choose smaller immediate rewards over larger delayed rewards. Delay
      discounting correlated with performance on executive functioning tasks.
      CONCLUSIONS: Increased discounting is associated with broad executive
      dysfunction, suggesting that HCV-associated executive dysfunction may lead to
      altered decision-making style.

PMID- 20694873
TI  - Medication and finance management among HIV-infected adults: the impact of age
      and cognition.
AB  - This study examined the effects of aging and cognitive impairment on medication
      and finance management in an HIV sample. We observed main effects of age (older <
      younger) and neuropsychological impairment on functional task performance.
      Interactions between age and cognition demonstrated that older impaired
      individuals performed significantly more poorly than all other comparison groups.
      There were no relationships between laboratory performance and self-reported
      medication and finance management. The interaction of advancing age and cognitive
      impairment may confer significant functional limitations for HIV individuals that
      may be better detected by performance-based measures of functional abilities
      rather than patient self-report.

PMID- 20694874
TI  - Community collaboration in a community H1N1 vaccination program.
AB  - This community's utilization of their Medical Reserve Corps (MRC) unit proved to
      be a valuable resource in their vaccination clinics as part of their response to
      the novel influenza A (H1N1) virus. Early planning, mock vaccination drills, and
      use of a strategic analysis process aided in the formulation and development of
      an efficient vaccination campaign.

PMID- 20694875
TI  - Postflood disaster management and the home health nurse: using theory to guide
      practice.
AB  - Few frameworks exist to guide home health nurses during the response and recovery
      phases of disasters such as flooding. The Double ABCX Model of Family Adaptation
      is offered as an example of a guiding framework for nurses in postflood
      management. Phases of the model are linked to the nursing process, and management
      strategies are applied to individuals and families living in the community.
      Postcrisis decision-making is detailed through the discussion of nursing
      diagnoses, interventions, and evaluation. Implications highlight the value of
      using a theoretical framework to guide practice, develop knowledge, and clarify
      the home health nurse's role in postflood management.

PMID- 20694876
TI  - A cost consequence analysis of outreach strategies for high risk pregnant women.
AB  - This retrospective, cost consequence analysis examined three distinct outreach
      strategies used by a community-based public health agency to enroll uninsured,
      low-income pregnant women in perinatal health care services. The three strategies
      included outreach workers, liaison workers, and case managers. Data analysis
      revealed that costs per enrollee by strategy were: outreach workers: $429;
      liaison workers: $98; and case managers: $187. Cost per strategy must be
      considered cautiously, however, because outreach and enrollment strategies at
      this agency are not mutually exclusive. Data analysis also revealed that the
      number of low and very low birth weight babies born to women enrolled in the
      study agency was half that of the general population, even though less than half
      the participants were enrolled in prenatal care during the first trimester of
      pregnancy. Findings from this study support the use of outreach and enrollment
      strategies to reduce barriers to access to health care and reduce health
      disparities of low-income, vulnerable populations.

PMID- 20694877
TI  - A welfare-to-wellness-to-work program.
AB  - This cross-sectional, exploratory study evaluates and describes a welfare-to
      wellness-to-work program developed by a nurse located in the western United
      States. Adults (N = 34) aged 23-57-years-old, who participated in the program
      from 2001 to 2007, completed a demographic/health survey and were interviewed.
      From open-ended, semistructured questions, the study identified key themes
      related to the program. Content analysis of the data revealed significant
      insights about the program's curriculum, positive changes for the participants,
      obstacles and challenges they confronted, employment success, and a motivational
      tool (affirmations). Participants gained overwhelming benefit from the program
      and enhanced their functioning as individuals, family members, and parents.

PMID- 20694878
TI  - Culturally sensitive community engaged research with African American young
      women: lessons learned.
AB  - The use of culturally sensitive research approaches is of paramount importance in
      conducting community-engaged research with African American communities. The
      purpose of this article is to describe the development and use of culturally and
      community sensitive research methods in a study to understand social messages
      about pregnancy and childbearing among low-income urban African American
      adolescent girls. Key elements of this community accepted focused ethnography
      study are described, including study design, recruitment, data collection, and
      analysis techniques.

PMID- 20694880
TI  - Kinetic study of laser-induced photocatalytic degradation of dye (alizarin
      yellow) from wastewater using nanostructured ZnO.
AB  - Nanoparticles of zinc oxide semiconductor were applied for removal of toxic
      organic pollutants such as dyes (alizarin yellow GG) from wastewater using laser
      induced photocatalytic process. A special photoreactor was designed for this
      purpose using local resources. Laser enhanced photo degradation of alizarin
      yellow GG (AYGG) was carried out by irradiating the contaminated aqueous solution
      with a 355 nm radiation generated from third harmonic of Nd:YAG laser. The effect
      of different operational parameters such as the initial dyes concentration, the
      concentration of photocatalyst, laser irradiation time, laser energy and pH on
      photocatalytic degradation of the dyes was investigated. It was observed that pH
      and the initial dyes concentration has a significant role in the dyes removal
      process. Using the optimum conditions (parameters), almost 90% degradation was
      achieved by nano ZnO in a short span of time. The efficiency achieved in this
      work using nano ZnO was much higher than micro ZnO catalyst and using
      conventional custom made setups. This is a first study of its kind where laser
      and nano ZnO particles have been employed for removal of dyes from wastewater.

PMID- 20694881
TI  - Spatial and temporal changes of water quality, and SWAT modeling of Vosvozis
      river basin, North Greece.
AB  - The results of an investigation of the quantitative and qualitative
      characteristics of Vosvozis river in Northern Greece is presented. For the
      purposes of this study, three gaging stations were installed along Vosvozis
      river, where water quantity and quality measurements were conducted for the
      period August 2005 to November 2006. Water discharge, temperature, pH, dissolved
      oxygen (DO) and electrical conductivity (EC) were measured in situ using
      appropriate equipment. The collected water samples were analyzed in the
      laboratory for the determination of nitrate, nitrite and ammonium nitrogen, total
      Kjeldalh nitrogen (TKN), orthophosphate (OP), total phosphorus (TP), COD, and
      BOD. Agricultural diffuse sources provided the major source of nitrate nitrogen
      loads during the wet period. During the dry period (from June to October), the
      major nutrient (N, P) and COD, BOD sources were point sources. The trophic status
      of Vosvozis river during the monitoring period was determined as eutrophic, based
      on Dodds classification scheme. Moreover, the SWAT model was used to simulate
      hydrographs and nutrient loads. SWAT was validated with the measured data.
      Predicted hydrographs and pollutographs were plotted against observed values and
      showed good agreement. The validated model was used to test eight alternative
      scenarios concerning different cropping management approaches. The results of
      these scenarios indicate that nonpoint source pollution is the prevailing type of
      pollution in the study area. The SWAT model was found to satisfactorily simulate
      processes in ephemeral river basins and is an effective tool in water resources
      management.

PMID- 20694882
TI  - Funnel-and-gate remediation systems augmented with passive filter wells.
AB  - The objective of this study was to evaluate the ability of funnel-and-gate
      structures augmented with passive wells containing filter cartridges to capture
      contaminated groundwater in hypothetical, homogeneous and heterogeneous,
      unconfined aquifers. Perpendicular to groundwater flow, linear structures were 15
      m wide, 1 m thick, and keyed into the base of the aquifer. Gates occupied 4 m of
      the total width of each simulated structure; one gate was 5 m from a contaminant
      plume's leading tip, while others occupied cross-gradient margins of the plume.
      Results suggest a modest reduction in remediation timeframes, up to 425 d per
      well added in these simulations; however, incremental benefits are highly
      variable and case specific.

PMID- 20694883
TI  - Arsenic remediation of drinking water using iron-oxide coated coal bottom ash.
AB  - We describe laboratory and field results of a novel arsenic removal adsorbent
      called 'Arsenic Removal Using Bottom Ash' (ARUBA). ARUBA is prepared by coating
      particles of coal bottom ash, a waste material from coal fired power plants, with
      iron (hydr)oxide. The coating process is simple and conducted at room temperature
      and atmospheric pressure. Material costs for ARUBA are estimated to be low
      (approximately $0.08 per kg) and arsenic remediation with ARUBA has the potential
      to be affordable to resource-constrained communities. ARUBA is used for removing
      arsenic via a dispersal-and-removal process, and we envision that ARUBA would be
      used in community-scale water treatment centers. We show that ARUBA is able to
      reduce arsenic concentrations in contaminated Bangladesh groundwater to below the
      Bangladesh standard of 50 ppb. Using the Langmuir isotherm (R(2) = 0.77) ARUBA's
      adsorption capacity in treating real groundwater is 2.6 x 10(- 6)mol/g (0.20
      mg/g). Time-to-90% (defined as the time interval for ARUBA to remove 90% of the
      total amount of arsenic that is removed at equilibrium) is less than 1 hour.
      Reaction rates (pseudo-second-order kinetic model, R(2) > or = 0.99) increase
      from 2.4 x 10(5) to 7.2 x 10(5) g mol(- 1)min(- 1) as the groundwater arsenic
      concentration decreases from 560 to 170 ppb. We show that ARUBA's arsenic
      adsorption density (AAD), defined as the milligrams of arsenic removed at
      equilibrium per gram of ARUBA added, is linearly dependent on the initial arsenic
      concentration of the groundwater sample, for initial arsenic concentrations of up
      to 1600 ppb and an ARUBA dose of 4.0 g/L. This makes it easy to determine the
      amount of ARUBA required to treat a groundwater source when its arsenic
      concentration is known and less than 1600 ppb. Storing contaminated groundwater
      for two to three days before treatment is seen to significantly increase ARUBA's
      AAD. ARUBA can be separated from treated water by coagulation and clarification,
      which is expected to be less expensive than filtration of micron-scale particles,
      further contributing to the affordability of a community-scale water treatment
      center.

PMID- 20694884
TI  - Comparison of amphipods Corophium insidiosum and C. orientale (Crustacea:
      Amphipoda) in sediment toxicity testing.
AB  - The aim of this study was to compare the sensitivity of two Corophidae: Corophium
      orientale a standardized species and Corophium insidiosum a species more
      available in the Ionian sea (Southern Italy), in order to evaluate the
      suitability and applicability of C. insidiosum to sediment toxicity test. The
      sensitivity of the 2 species was compared through simultaneous bioassays: the 96
      h static water-only toxicity test and a 10-day static sediment toxicity test.
      Sediment samples were collected in the Livorno harbour (Ligurian Sea). Both
      amphipods showed high sensitivity to reference toxicant and no significant
      differences were found between the two Corophiidae (t test; p > 0.05). Numerical
      Sediment Quality Guidelines (SQGs) have been used to relate the chemical
      concentrations of sediment samples to biological effects. Both amphipod species
      indicated the same sediment samples as potentially toxic according to chemical
      data. The results indicate that Corophium insidiosum would be suitable as an
      alternative test species to the recommended species C. orientale, in the
      development of sediment toxicity test.

PMID- 20694885
TI  - Maternal exposure to low-level heavy metals during pregnancy and birth size.
AB  - We evaluated the effect of environmental, low-level exposure to heavy metals
      during pregnancy, as estimated by urine analysis, on birth size of the newborns.
      Spot urine samples were collected from unexposed 78 pregnant women in Tokyo
      during 2007 and 2008. The urinary concentrations of beryllium (Be), copper (Cu),
      arsenic (As), zinc (Zn), selenium (Se), molybdenum (Mo), cadmium (Cd), tin (Sn),
      antimony (Sb), and lead (Pb) were measured by ICP-MS. The birthweight (BW),
      length (BL) and head circumference (HC) of the newborns delivered to the subjects
      were measured and relationship with urinary metal concentration was examined. The
      geometric mean concentration of urinary Be, Cu, As, Zn, Se, Mo, Cd, Sn, Sb, and
      Pb were 0.031, 12.8, 393, 76.9, 37.6, 79.0, 0.766, 0.232, < 0.21, 0.483 microg g
      creatinine(-1), respectively. The mean birth size of the newborn was close to the
      national average value in Japan. Stepwise multiple regression analysis using
      birth size as a dependent variable and urinary metal concentrations and
      covariates as independent variables extracted urinary Cd with a significant
      negative standardized partial regression coefficient (beta) for BW along with
      gestational age and maternal BMI. For HC, Sn was selected with a negative beta.
      The present study suggested that even a low-level Cd body burden of general
      population has slight but significant negative effect on BW.

PMID- 20694886
TI  - Inhalation exposure to jet fuel (JP8) among U.S. Air Force personnel.
AB  - As jet fuel is a common occupational exposure among military and civilian
      populations, this study was conducted to characterize jet fuel (JP8) exposure
      among active duty U.S. Air Force personnel. Personnel (n = 24) were divided a
      priori into high, moderate, and low exposure groups. Questionnaires and personal
      air samples (breathing zone) were collected from each worker over 3 consecutive
      days (72 worker-days) and analyzed for total hydrocarbons (THC), benzene,
      toluene, ethylbenzene, xylenes, and naphthalene. Air samples were collected from
      inside the fuel tank and analyzed for the same analytes. Linear mixed-effects
      models were used to evaluate the exposure data. Our results show that the
      correlation of THC (a measure of overall JP8 inhalation exposure) with all other
      analytes was moderate to strong in the a priori high and moderate exposure groups
      combined. Inhalation exposure to all analytes varied significantly by self
      reported JP8 exposure (THC levels higher among workers reporting JP8 exposure), a
      priori exposure group (THC levels in high group > moderate group > low group),
      and more specific job task groupings (THC levels among workers in fuel systems
      hangar group > refueling maintenance group > fuel systems office group > fuel
      handling group > clinic group), with task groupings explaining the most between
      worker variability. Among highly exposed workers, statistically significant job
      task-related predictors of inhalation exposure to THC indicated that increased
      time in the hangar, working close to the fuel tank (inside > less than 25 ft >
      greater than 25 ft), primary job (entrant > attendant/runner/fireguard > outside
      hangar), and performing various tasks near the fuel tank, such as searching for a
      leak, resulted in higher JP8 exposure. This study shows that while a priori
      exposure groups were useful in distinguishing JP8 exposure levels, job task-based
      categories should be considered in epidemiologic study designs to improve
      exposure classification. Finally, the strong correlation of THC with naphthalene
      suggests that naphthalene may be an appropriate surrogate of JP8 exposure.
      [Supplementary materials are available for this article. Go to the publisher's
      online edition of the Journal of Occupational and Environmental Hygiene for the
      following free supplemental resource: a pdf file containing a table detailing
      concentrations of JP8 components.].

PMID- 20694887
TI  - Effect of drink temperature on core temperature and endurance cycling performance
      in warm, humid conditions.
AB  - The aims of this study were to determine the effect of cold (4  degrees C) and
      thermoneutral (37  degrees C) beverages on thermoregulation and performance in
      the heat and to explore sensory factors associated with ingesting a cold
      stimulus. Seven males (age 32.8 +/- 6.1 years, [V(.)]O(2peak) 59.4 +/- 6.6 ml x
      kg(-1) x min(-1)) completed cold, thermoneutral, and thermoneutral + ice trials
      in randomized order. Participants cycled for 90 min at 65%[V(.)]O(2peak) followed
      by a 15-min performance test at 28  degrees C and 70% relative humidity. They
      ingested 2.3 ml x kg(-1) of a 7.4% carbohydrate-electrolyte solution every 10 min
      during the 90-min steady-state exercise including 30 ml ice puree every 5 min in
      the ice trial. Absolute changes in skin temperature (0.22 +/- 1.1  degrees C vs.
      1.14 +/- 0.9  degrees C; P = 0.02), mean body temperature (1.2 +/- 0.3 vs. 1.6 +/
      0.3  degrees C; P = 0.03), and heat storage were lower across the 90-min
      exercise bout for the cold compared with the thermoneutral trial. Significant
      improvements (4.9 +/- 2.4%, P < 0.01) in performance were observed with cold but
      no significant differences were detected with ice. Consumption of cold beverages
      during prolonged exercise in the heat improves body temperature measures and
      performance. Consumption of ice did not reveal a sensory response, but requires
      further study. Beverages consumed by athletes exercising in the heat should
      perhaps be cold for performance and safety reasons.

PMID- 20694888
TI  - Playing level achieved, throwing history, and humeral torsion in Masters baseball
      players.
AB  - Humeral torsion is thought to be beneficial for throwing. To examine this
      hypothesis, the throwing and non-throwing arms of 84 Masters baseball players
      over 35 years of age were measured for humeral torsion, and the highest playing
      level they achieved and their playing history were recorded. Regression analyses
      were used to obtain predictors of the highest playing level achieved, throwing
      arm humeral torsion, and side-to-side difference in humeral torsion. Equations
      accounting for 36%, 46%, and 12% of the variance respectively were produced.
      Achieving representative level playing status was associated with the number of
      seasons played under 16 years of age and having greater throwing arm humeral
      retrotorsion. Throwing arm humeral retrotorsion was associated with non-throwing
      arm humeral retrotorsion and an increased number of seasons played before the age
      of 16 years. A model in which repeated throwing develops an adaptive unilateral
      bone torsion along with growth in baseball expertise is proposed. Thus dominant
      arm humeral retrotorsion is a predictor of highest baseball playing level
      achieved, which in turn is influenced by genetic endowment (as seen in the
      torsion of the non-throwing arm) and amount of throwing activity, particularly
      prior to the age of 16.

PMID- 20694889
TI  - Anthropology is missing: on the World Development Report 2010: Development and
      Climate Change.
AB  - When the World Bank publishes a report on climate change, the world takes notice.
      What are its diagnoses and treatments, and how present is anthropology in this
      analysis? The 2010 World Development Report on climate change provides few new
      diagnostic tools and no clear Bank policy revisions. It often fails to harmonize
      neoliberal development rhetoric with new climate-change imperatives. It nods to
      the importance of social context and risk perception yet refers primarily to
      behavioral economics and psychological constructs. Although anthropologists are
      documenting the local effects and human responses to larger-scale, climate-driven
      processes, our work is absent in the report. To play a role at global scale we
      would do well to learn more about concepts like nonlinearity and emergence,
      systems analysis, modeling, and disease dynamics. Our adroitness in developing
      metaphors and methods for crossing scale will make our efforts more visible and
      applicable.

PMID- 20694890
TI  - Chinese medicine in action: on the postcoloniality of medical practice in China.
AB  - Since the early twentieth century, there has been strong opposition to Chinese
      medicine within Chinese society. Critics have attacked Chinese medicine as
      unscientific and a hindrance to the development of the nation. I argue that
      doctors of Chinese medicine have responded to this charge by developing a
      "postcolonial" form of medicine that is based on the celebrated methodology of
      "pattern recognition and treatment determination bianzheng lunzhi [image
      omitted]." I show that bianzheng lunzhi plays two contradictory roles in everyday
      clinical practice, distinguishing the uniqueness of Chinese medicine from
      biomedicine while providing a technology for integrating these two medical
      practices. Through the close examination of a typical medical case, I show how
      these dual processes of purification and hybridization have become the central
      dynamic in the postcolonial transformation of Chinese medicine.

PMID- 20694891
TI  - Holistic medicine not "torture": performing acupuncture in Galway, Ireland.
AB  - This article examines how the aesthetic design of clinics and interactive
      discourse and rituals construct the social reality of acupuncture sessions as a
      form of holistic medical therapy. Verbal and nonverbal interactions create an
      appealing medical environment but also help prevent the emergence of undesired
      counter-realities (e.g., pain, biomedical intervention). Based on observations of
      acupuncture sessions conducted in Galway, Ireland, I illustrate how ambiance and
      aesthetic elements of clinics create a complex medico-cultural environment that
      balances oppositional associations (Western/non-Western, exoticism/convention,
      medical alterity/medical professionalism). Patients interviewed continually
      referred to acupuncture as a natural and non-invasive form of medical treatment.
      This suggests that interpersonal discourse and aesthetic design play key roles in
      how patients define acupuncture treatment, and that these ephemeral agents may
      also influence how patients come to define efficacy.

PMID- 20694892
TI  - Contestations over "tradition" and "culture" in a time of AIDS.
AB  - In Malawi, the distress and unease caused by rising numbers of deaths and chronic
      illness due to HIV infection have led people to search for explanations. Here, we
      describe two particular "turns to culture." Zomba villagers over two decades have
      come to link AIDS with kanyera, an indigenous illness syndrome. In contrast, the
      public media, government, and donors blame "promiscuity" and "cultural practices"
      for HIV infection. The resulting stigmatization causes people to avoid naming
      AIDS, and both turns to culture tend to link blame and stigma to women.

PMID- 20694893
TI  - It gets better if you do? Measuring quality care in Puerto Rico.
AB  - Quantifying quality is supposed to unite health policy, health plans, and health
      care consumers in a circuit of constant improvement. In practice, significant
      gulfs separate how policymakers, health plan administrators, and consumers write
      and talk about quality. Drawing on policy literature, ethnography inside a
      managed care organization, and interviews with health plan members, this article
      examines a quality improvement program at a health plan in Puerto Rico. The
      findings challenge the assumption underwriting neoliberal health policy that
      quality measurement leads to quality improvement.

PMID- 20694894
TI  - Patient willingness to be seen by physician assistants, nurse practitioners, and
      residents in the emergency department: does the presumption of assent have an
      empirical basis?
AB  - Physician assistants (PAs), nurse practitioners (NPs), and medical residents
      constitute an increasingly significant part of the American health care
      workforce, yet patient assent to be seen by nonphysicians is only presumed and
      seldom sought. In order to assess the willingness of patients to receive medical
      care provided by nonphysicians, we administered provider preference surveys to a
      random sample of patients attending three emergency departments (EDs).
      Concurrently, a survey was sent to a random selection of ED residents and PAs.
      All respondents were to assume the role of patient when presented with
      hypothetical clinical scenarios and standardized provider definitions. Despite
      presumptions to the contrary, ED patients are generally unwilling to be seen by
      PAs, NPs, and residents. While seldom asked in practice, 79.5% of patients fully
      expect to see a physician regardless of acuity or potential for cost savings by
      seeing another provider. Patients are more willing to see residents than
      nonphysicians.

PMID- 20694895
TI  - Translational research beyond approval: a two-stage ethics review.

PMID- 20694896
TI  - Responses to open peer commentaries on "research exceptionalism".

PMID- 20694897
TI  - The ethics of substituting physician assistants, nurse practitioners, and
      residents for attending physicians.

PMID- 20694898
TI  - Nurse practitioners: what does the public need to know?

PMID- 20694899
TI  - Is it reasonable to refuse to be seen by a nurse practitioner in the emergency
      department?

PMID- 20694900
TI  - Doctors, patients, and the ED: the resident's role.

PMID- 20694901
TI  - The diverse ethics of translational research.
AB  - Commentators on the ethics of translational research find it morally problematic.
      Types of translational research are said to involve questionable benefits,
      special risks, additional barriers to informed consent, and severe conflicts of
      interest. Translational research conducted on the global poor is thought to
      exploit them and increase international disparities. Some commentators support
      especially stringent ethical review. However, such concerns are grounded only in
      pre-approval translational research (now called T1). Whether or not T1 has these
      features, translational research beyond approval (T2: phase IV, health services,
      and implementation research) is unlikely to and, when conducted on the global
      poor, may support development. Therefore, insofar as T1 is morally problematic,
      and no independent objections to T2 exist, the ethics of translational research
      is diverse: while some translational research is problematic, some is not.
      Funding and oversight should reflect this diversity, and T2 should be encouraged,
      particularly when conducted among the global poor.

PMID- 20694902
TI  - The ethical urgency of advancing implementation science.

PMID- 20694903
TI  - Ethical analysis of translational research is more complex than distinguishing T1
      from T2.

PMID- 20694904
TI  - Bioethics and post-approval research in translational science.

PMID- 20694905
TI  - Community engagement and the ethics of global, translational research: a response
      to Sofaer and Eyal.

PMID- 20694906
TI  - Impediments to "T2" research: are ethics really to blame?

PMID- 20694907
TI  - Diverse ethics of translational research in the developing world.

PMID- 20694908
TI  - Post-approval translational research itself has diverse ethics.

PMID- 20694909
TI  - Research exceptionalism.
AB  - Research involving human subjects is much more stringently regulated than many
      other nonresearch activities that appear to be at least as risky. A number of
      prominent figures now argue that research is overregulated. We argue that the
      reasons typically offered to justify the present system of research regulation
      fail to show that research should be subject to more stringent regulation than
      other equally risky activities. However, there are three often overlooked reasons
      for thinking that research should be treated as a special case. First, research
      typically involves the imposition of risk on people who do not benefit from this
      risk imposition. Second, research depends on public trust. Third, the complexity
      of the moral decision making required favors ethics committees as a regulative
      solution for research.

PMID- 20694910
TI  - The recipe for overreaching regulation.

PMID- 20694911
TI  - Civic trust, scientific objectivity, and the publicity condition.

PMID- 20694912
TI  - Beyond research exceptionalism: a call for process redesign.

PMID- 20694913
TI  - One size does not fit all: the ethical imperative to limit the concept of
      research exceptionalism.

PMID- 20694914
TI  - Not all human subjects research is exceptional.

PMID- 20694915
TI  - Assessing the case for the regulation of research.

PMID- 20694916
TI  - Striking the right balance in research ethics and regulation.

PMID- 20694917
TI  - Reversing "research exceptionalism".

PMID- 20694918
TI  - Three worries about three arguments for research exceptionalism.

PMID- 20694919
TI  - Simultaneity and temporal order perception: Different sides of the same coin?
      Evidence from a visual prior-entry study.
AB  - Attended stimuli are perceived as occurring earlier than unattended stimuli. This
      phenomenon of prior entry is usually identified by a shift in the point of
      subjective simultaneity (PSS) in temporal order judgements (TOJs). According to
      its traditional psychophysical interpretation, the PSS coincides with the
      perception of simultaneity. This assumption is, however, questionable.
      Technically, the PSS represents the temporal interval between two stimuli at
      which the two alternative TOJs are equally likely. Thus it also seems possible
      that observers perceive not simultaneity, but uncertainty of temporal order. This
      possibility is supported by prior-entry studies, which find that perception of
      simultaneity is not very likely at the PSS. The present study tested the percept
      at the PSS in prior entry, using peripheral cues to orient attention. We found
      that manipulating attention caused varying temporal perceptions around the PSS.
      On some occasions observers perceived the two stimuli as simultaneous, but on
      others they were simply uncertain about the order in which they had been
      presented. This finding contradicts the implicit assumption of most models of
      temporal order perception, that perception of simultaneity inevitably results if
      temporal order cannot be discriminated.

PMID- 20694920
TI  - Follow you, follow me: continuous mutual prediction and adaptation in joint
      tapping.
AB  - To study the mechanisms of coordination that are fundamental to successful
      interactions we carried out a joint finger tapping experiment in which pairs of
      participants were asked to maintain a given beat while synchronizing to an
      auditory signal coming from the other person or the computer. When both were
      hearing each other, the pair became a coupled, mutually and continuously adaptive
      unit of two "hyper-followers", with their intertap intervals (ITIs) oscillating
      in opposite directions on a tap-to-tap basis. There was thus no evidence for the
      emergence of a leader-follower strategy. We also found that dyads were equally
      good at synchronizing with the irregular, but responsive other as with the
      predictable, unresponsive computer. However, they performed worse when the
      "other" was both irregular and unresponsive. We thus propose that interpersonal
      coordination is facilitated by the mutual abilities to (a) predict the other's
      subsequent action and (b) adapt accordingly on a millisecond timescale.

PMID- 20694921
TI  - Ideomotor effects of pitch on continuation tapping.
AB  - The ideomotor principle predicts that perception will modulate action where
      overlap exists between perceptual and motor representations of action. This
      effect is demonstrated with auditory stimuli. Previous perceptual evidence
      suggests that pitch contour and pitch distance in tone sequences may elicit tonal
      motion effects consistent with listeners' implicit awareness of the lawful
      dynamics of locomotive bodies. To examine modulating effects of perception on
      action, participants in a continuation tapping task produced a steady tempo.
      Auditory tones were triggered by each tap. Pitch contour randomly and
      persistently varied within trials. Pitch distance between successive tones varied
      between trials. Although participants were instructed to ignore them, tones
      systematically affected finger dynamics and timing. Where pitch contour implied
      positive acceleration, the following tap and the intertap interval (ITI) that it
      completed were faster. Where pitch contour implied negative acceleration, the
      following tap and the ITI that it completed were slower. Tempo was faster with
      greater pitch distance. Musical training did not predict the magnitude of these
      effects. There were no generalized effects on timing variability. Pitch contour
      findings demonstrate how tonal motion may elicit the spontaneous production of
      accents found in expressive music performance.

PMID- 20694922
TI  - Elucidating the effects of ageing on remembering perceptually distorted word
      pairs.
AB  - We investigated the effects of age, background babble, and acoustic distortion of
      the word itself on serial position memory in a series of experiments involving
      six different auditory environments (quiet, and 12-talker background babble
      presented between, overlapping, or concurrent with word presentation or with two
      kinds of distortion applied to the words). To control for hearing, the level of
      babble or distortion was adjusted so that younger and older adults could hear the
      words equally well. Although the presence of continuous and word-flanking
      background babble adversely affected memory in the early serial positions in both
      age groups, only older adults' memory was adversely affected in the later serial
      positions. Moreover, younger adults' memory was not affected by acoustic word
      distortion, whereas one of the two types of temporal distortion adversely
      affected memory for later serial positions in older adults. The exact pattern of
      impairment and its interaction with age suggests that memory in older adults is
      more affected than that in younger adults in complex listening situations because
      they either need more time or have to employ more attentional resources to
      segregate different auditory streams, thereby depleting the pool of resources
      available for memory encoding.

PMID- 20694923
TI  - Hygiene and cleanability: a focus on surfaces.
AB  - Hygiene is a permanent concern for food industries since they must commercialize
      high quality products in order to comply with the legislation and the
      expectations of the consumers. The hygienic state of a surface is thus a critical
      parameter with respect to the performances of the production process and to the
      final quality of the product. For this reason, cleaning and disinfection are
      essential. However, the efficiency of the cleaning process will not only depend
      on the optimization of the process by itself and on the equipment design but also
      on the characteristics of the soiled surface i.e. mainly its roughness, surface
      chemical composition, and surface energy. The relation between these parameters
      and the cleanability are presented here, mainly for food applications. Some
      examples of existing easy-to-clean and self-cleaning surfaces based on the
      modification of these surface parameters are also presented.

PMID- 20694924
TI  - Prediction of in vivo short-chain fatty acid production in hindgut fermenting
      mammals: problems and pitfalls.
AB  - Short-chain fatty acids (SCFA) are considered to have important physiological
      functions. However, to prove this, SCFA must be determined, which is rather
      difficult as a lot of factors interfere with their production. This review
      focuses on the factors that influence the prediction of short-chain fatty acid
      formation in the large intestine of monogastric mammals. To mimic the in vivo
      situation, when predicting the amount of short-chain fatty acids produced from a
      certain substrate based on in vitro models, one has to estimate the amount of
      this substrate entering the large intestine, the retention time in the different
      parts of the large intestine, and the substrate fermentability. Instead of in
      vitro models, direct and indirect techniques may be used to measure short-chain
      fatty acid production in vivo. Direct techniques include the measurement of input
      and output or measuring differences in SCFA between portal and venous blood
      whereas indirect techniques measure the end products of fermentation. In this
      case, other factors have to be taken into account, including technical
      limitations and ethical considerations. In this review it is concluded that the
      choice for a method will rely on the purpose of the study taking into account the
      (dis)advantages of every method.

PMID- 20694925
TI  - Plant metabolism and the environment: implications for managing phenolics.
AB  - The presence of phenolic compounds in food has garnered much attention over the
      years. The diversity of these compounds and their contribution to nutritive and
      sensory qualities has been investigated in depth to elucidate benefits and modes
      of action. This review is intended to provide information on the impact of
      growing conditions on the accumulation of phenolics in plants. The aim is to
      provide knowledge of factors that influence phenolic biosynthesis in plants to
      help us manage them prior to harvest. Through improving our understanding of
      plant responses to the environment we may be able to manipulate growing
      parameters to suit the needs of the consumer. In this review, research regarding
      plant responses to climate, farming practices, biotic, and abiotic stresses is
      presented.

PMID- 20694926
TI  - Meat shelf-life and extension using collagen/gelatin coatings: a review.
AB  - Different factors lead to the end of shelf-life for fresh meat products. The
      factors depend upon the animal including breed difference and muscle fiber type,
      external influences such as diet and stress, and post-harvest storage conditions
      including time, temperature, and packaging atmosphere. The characteristics that
      indicate the end of shelf-life for fresh meat products include water loss/purge
      accumulation, color deterioration due to myoglobin oxidation, rancidity due to
      lipid oxidation, and microbial spoilage. The characteristics can be measured and
      studied in the laboratory. Meat shelf-life is extended with the application of a
      surface coating because it provides a water and oxygen barrier. Collagen and
      gelatin coatings are used as a barrier on meat products to reduce purge, color
      deterioration, aroma deterioration, and spoilage, improve sensory scores, and act
      as an antioxidant.

PMID- 20694927
TI  - Nigella sativa: reduces the risk of various maladies.
AB  - Coinage of terms like nutraceuticals, functional, and pharma foods has diverted
      the attention of human beings to where they are seeking more natural cures.
      Though pharmaceutical drugs have been beneficial for human health and have cured
      various diseases but they also impart some side effects. Numerous plants have
      been tested for their therapeutic potential; Nigella sativa, commonly known as
      black cumin, is one of them. It possesses a nutritional dense profile as its
      fixed oil (lipid fraction), is rich in unsaturated fatty acids while essential
      oil contains thymoquinone and carvacrol as antioxidants. N. sativa seeds also
      contain proteins, alkaloids (nigellicines and nigelledine), and saponins (alpha
      hederin) in substantial amounts. Recent pharmacological investigations suggested
      its potential role, especially for the amelioration of oxidative stress through
      free radical scavenging activity, the induction of apoptosis to cure various
      cancer lines, the reduction of blood glucose, and the prevention of complications
      from diabetes. It regulates hematological and serological aspects and can be
      effective in dyslipidemia and respiratory disorders. Moreover, its
      immunopotentiating and immunomodulating role brings balance in the immune system.
      Evidence is available supporting the utilization of Nigella sativa and its
      bioactive components in a daily diet for health improvement. This review is
      intended to focus on the composition of Nigella sativa and to elaborate its
      possible therapeutic roles as a functional food to prevent an array of maladies.

PMID- 20694928
TI  - Bioactive compounds in cranberries and their biological properties.
AB  - Cranberries are healthy fruit that contribute color, flavor, nutritional value,
      and functionality. They are one of only three fruits native to America. Over the
      past decade, public interest for the North American cranberry (Vaccinium
      macrocarpon) has been rising with reports of their potential health benefits
      linked to the numerous phytochemicals present in the fruit--the anthocyanins, the
      flavonols, the flavan-3-ols, the proanthocyanidins, and the phenolic acid
      derivatives. The presence of these phytochemicals appears to be responsible for
      the cranberry property of preventing many diseases and infections, including
      cardiovascular diseases, various cancers, and infections involving the urinary
      tract, dental health, and Helicobacter pylori-induced stomach ulcers and cancers.
      Recent years have seen important breakthroughs in our understanding of the
      mechanisms through which these compounds exert their beneficial biological
      effects, yet these remain to be scientifically substantiated. In this paper these
      characteristics, as well as the antioxidant, radical scavenging, antibacterial,
      antimutagen, and anticarcinogen properties of cranberry major bioactive compounds
      are explained.

PMID- 20694929
TI  - Proteomics for the food industry: opportunities and challenges.
AB  - In this review, we outline the state-of-the-art of proteomic techniques and their
      application within the plant-based food industry. The relevance of high
      throughput proteomic approaches is to increase insight and understanding of how
      food processing is affected by the physiology of the product and through this, to
      enable the optimization of the overall food production process. Food areas with
      large potential for application of proteomics technologies are discussed,
      including novel and controversial areas such as food irradiation, GMOs, non
      thermal processing, obesity, and functional foods.

PMID- 20694930
TI  - Microarray technology: a promising tool in nutrigenomics.
AB  - Microarray technology is a powerful tool for the global evaluation of gene
      expression profiles in tissues and for understanding many of the factors
      controlling the regulation of gene transcription. This technique not only
      provides a considerable amount of information on markers and predictive factors
      that may potentially characterize a specific clinical picture, but also promises
      new applications for therapy. One of the most recent applications of microarrays
      concerns nutritional genomics. Nutritional genomics, known as nutrigenomics, aims
      to identify and understand mechanisms of molecular interaction between nutrients
      and/or other dietary bioactive compounds and the genome. Actually, many
      nutrigenomic studies utilize new approaches such as microarrays, genomics, and
      bioinformatics to understand how nutrients influence gene expression. The
      coupling of these new technologies with nutrigenomics promises to lead to
      improvements in diet and health. In fact, it may provide new information which
      can be used to ameliorate dietary regimens and to discover novel natural agents
      for the treatment of important diseases such as diabetes and cancer. This
      critical review gives an overview of the clinical relevance of a nutritional
      approach to several important diseases, and proposes the use of microarray for
      nutrigenomic studies.

PMID- 20694932
TI  - Removal and leakage of environmental tobacco smoke from a model smoking room.
AB  - Experimental studies on the removal of accumulated environmental tobacco smoke
      (ETS) and the effectiveness of ETS leakage control were carried out in a model
      smoking room using carbon monoxide, nicotine, 3-ethenylpyridine, respirable
      suspended particulates, and ultrafine particles (UFP) as the ETS tracers. The
      study investigated the effectiveness of the designated smoking room, equipped
      with a displacement ventilation system under different ventilation rates (10-58
      L/sec per person,) in removing the ETS tracers. The extent of ETS leakage through
      different door operating scenarios under various ventilation rates was
      intensively studied. In particular, a manikin installed on a motorized rail was
      used to study the effect of human movement on the leakage of the ETS tracers. A
      double-door anteroom design was incorporated into the smoking room to study its
      effectiveness in ETS leakage prevention. It shows that at least 5 Pa of negative
      pressure, a fresh air supply rate 3-5 times higher than a typical office, direct
      air exhaust without air recirculation, and keeping the door closed are important
      for reducing ETS leakage. However, with the smokers moving in and out and the
      opening of the door, noticeable leakage of ETS can occur. The double-door
      anteroom design can improve leakage prevention. Among the five tracers, nicotine
      required the longest purging time to remove, after the smoking activity was
      stopped in the smoking room, due to its highly sorptive property. At least 4.4-6
      hr of purging is needed for minimizing ETS exposure by non-smokers entering the
      smoking room. The peak size of particulate matter inside the smoking room is
      about 80-100 nm, suggesting the importance of including UFP as an indicator for
      monitoring the exposure and leakage of ETS. The impact of manikin movement on
      contaminant transport was studied, providing useful information on the effects of
      human activities on indoor air quality multicompartmental modeling.

PMID- 20694933
TI  - Development of the talent development environment questionnaire for sport.
AB  - As sporting challenge at the elite level becomes ever harder, maximizing
      effectiveness of the talent development pathway is crucial. Reflecting this need,
      this paper describes the development of the Talent Development Environment
      Questionnaire, which has been designed to facilitate the development of sporting
      potential to world-class standard. The questionnaire measures the experiences of
      developing athletes in relation to empirically identified "key features" of
      effective talent development environments. The first phase involved the
      generation of questionnaire items with clear content and face validity. The
      second phase explored the factor structure and reliability. This was carried out
      with 590 developing athletes through application of exploratory factor analysis
      with oblique rotation, principal axis factoring extraction and cronbach alpha
      tests. This yielded a 59-item, seven-factor structure with good internal
      consistency (0.616-0.978). The Talent Development Environment Questionnaire
      appears to be a promising psychometric instrument that can potentially be useful
      for education and formative review in applied settings, and as a measurement tool
      in talent development research.

PMID- 20694934
TI  - Examination of adolescents' screen time and physical fitness as independent
      correlates of weight status and blood pressure.
AB  - Physical fitness performance is an important health correlate yet is often
      unrelated to sedentary behaviour in early adolescence. In this study, we examined
      the association of sedentary behaviour (i.e. screen time) with weight-related
      health markers and blood pressure, after controlling for cardiorespiratory
      fitness performance. American middle school students (N = 153, 56% females) aged
      11-15 years (mean 12.6 years, s = 0.5) completed assessments of cardiorespiratory
      fitness performance, screen time, weight status (BMI percentile, waist-to-height
      ratio), and blood pressure. Multivariate analysis of covariance, controlling for
      cardiorespiratory fitness performance, found those who met the daily
      recommendation of 2 h or less of screen time (n = 36, 23.5%) had significantly
      lower BMI (p < 0.05) and systolic blood pressure (p < 0.01) compared with those
      who exceeded this recommendation. Findings suggest specific intervention
      programmes may be designed to target both cardiorespiratory fitness and sedentary
      behaviours to maximize early adolescent health because these behaviours are
      likely to have unique and independent effects on youth health markers.

PMID- 20694935
TI  - Trunk extensor and flexor strength of long-distance race car drivers and
      physically active controls.
AB  - Seventy percent of motor sports athletes report low back pain. Information on the
      physical capacity of race car drivers is limited. The purpose of this study was
      to compare the maximum trunk extensor and flexor strength of elite race car
      drivers and physically active controls. Thirteen elite race car drivers and 13
      controls were measured in concentric mode for maximal trunk flexion and extension
      at 60 degrees  x s(-1) and 120 degrees  x s(-1). Peak torque (mean +/- s) at 60
      degrees  x s(-1) in trunk extension was 283 +/- 80 N x m in the drivers and 260
      +/- 88 N x m in controls (P > 0.05). At 120 degrees  x s(-1), drivers produced
      peak torques of 248 +/- 55 N x m compared with 237 +/- 74 N x m for controls (P >
      0.05). Peak torques in flexion were less than in extension for both groups (60
      degrees  x s(-1): drivers 181 +/- 56 N x m, controls 212 +/- 54 N x m, P > 0.05;
      120 degrees  x s(-1): drivers 191 +/- 57 N x m, controls 207 +/- 48 N x m, P >
      0.05). Individual ratios of flexion to extension forces exhibited ratios of 0.88
      (60 degrees  x s(-1)) and 0.93 (120 degrees  x s(-1)) for controls and 0.66 (60
      degrees  x s(-1)) and 0.77 (120 degrees  x s(-1)) for drivers (60 degrees  x s(
      1): P > 0.05; 120 degrees  x s(-1): P > 0.05). The maximum strength performance
      capacity of the trunk muscles of elite motor sport athletes competing in long
      distance racing did not differ from that of anthropometrically matched and
      physically active controls.

PMID- 20694936
TI  - Terrorists brought down the plane!--No, actually it was a technical fault:
      processing corrections of emotive information.
AB  - It is well known that people often continue to rely on initial misinformation
      even if this information is later corrected and even if the correction itself is
      remembered. This article investigated the impact of emotionality of the material
      on people's ability to discount corrected misinformation. The focus was on
      moderate levels of emotionality comparable to those elicited by real-world news
      reports. Emotionality has frequently been shown to have an impact upon reasoning
      and memory, but the generality of this influence remains unclear. In three
      experiments, participants read a report of a fictitious plane crash that was
      initially associated with either an emotionally laden cause (terrorist attack) or
      an emotionally more neutral cause (bad weather). This initial attribution was
      followed by a retraction and presentation of an alternative cause (faulty fuel
      tank). The scenarios demonstrably affected participants' self-reported feelings.
      However, all three experiments showed that emotionality does not affect the
      continued influence of misinformation.

PMID- 20694937
TI  - [Which properties are necessary for a marker in early and differential diagnosis
      of neurodegenerative disease?].

PMID- 20694938
TI  - [Depression in Parkinson's disease--Part 2: Therapy and management].
AB  - A good number of different methods and antidepressive agents are now available
      for the management of depressive symptoms, the efficacy of which has been
      confirmed by clinical studies. Various approaches--be it medication,
      electroconvulsive therapy (ECT), psychoeducation and psychotherapy--have also
      been developed to treat depression in patients with Parkinson's disease.
      Unfortunately, only a few controlled studies exist for this very specific group
      of patients. Systematic knowledge of treatment options, however, is lacking.
      Efficient management of depressive symptoms is absolutely indispensable
      considering the proven impact of a depression on the patients' quality of life.
      So far, more than half of the patients afflicted with Parkinson's disease and
      depression do not receive proper antidepressive therapy. This survey gives an
      overview on the pharmacological, somatic and psychological procedures of
      treatment applied in this group of patients, along with useful suggestions.

PMID- 20694939
TI  - [Recovery and remission in schizophrenia. Results from a naturalistic 2-year
      follow-up inpatient study].
AB  - INTRODUCTION: Remission in schizophrenia is defined as a period of at least 6
      months in which symptom reduction occurs. In comparison, the term recovery is
      defined to include not only long-term symptomatic improvement but also good
      psychosocial functioning and improved quality of life. The aim of this
      naturalistic study is to prospectively investigate all these variables and their
      interrelationship in a sample of subjects with schizophrenia over a period of two
      years. METHODS: Seventy-seven subjects were included into the analysis. Criteria
      of remission for each domain were assessed using the BPRS (brief psychiatric
      rating scale, symptomatic remission), GAF (global assessment of functioning,
      functional remission) and the SWN-K (subjective well-being under neuroleptics,
      remission of subjective well-being). Subjects were considered to have "recovered"
      if they remitted in all three domains at discharge (t0), one (t1) and two-year
      (t2) follow-up assessments. RESULTS: Symptomatic and functional remissions were
      rare and occurred only in 10 % of the subjects at t0, t1 and t2. Approximately
      one-third of the individuals had remission with a stable quality of life.
      Correlations between quality of life and functional and symptomatic remissions
      were weak. None of the subjects met the criteria for recovery. CONCLUSION:
      Compared to previous studies, the rates of remission and recovery in the current
      sample were quite low. The contrasting results may be due to the naturalistic
      characteristics of this sample of initially inpatient subjects while previous
      studies investigated selected samples of schizophrenic individuals. However,
      despite their functional and symptomatic impairments, the results also indicate
      that the schizophrenic subjects have a largely satisfying quality of life.

PMID- 20694940
TI  - [Expert opinion on post-traumatic stress disorder].
AB  - There is a high prevalence of post-traumatic stress disorder in community-based
      samples.Therefore, psychiatric assessment and expert opinion are often required.
      Professional standards for psychiatric expert opinion in the assessment of post
      traumatic stress disorder are outlined. The significance of symptom validity
      tests is critically discussed. Test results have to be considered carefully in
      the medicolegal context and require thorough clinical assessment.

PMID- 20694941
TI  - [Phraseology of disk herniation: an inevitable revision renaming the posterior
      disk prolapse--retrolapse is better].
AB  - Etymology teaches us to use the term prolapse exclusively for describing the part
      of the intervertebral disk that has slipped forwards, that is, towards the
      anterior longitudinal ligament. Consequently, the word retrolapse has to be
      introduced as the corresponding term in order to designate the posterior slipped
      disk. The common use of matching pairs like propulsion/retropulsion or
      prognathism/retrognathia is another justification for the recommended revision.

PMID- 20694943
TI  - [Olfactory dysfunction in parkinsonian syndromes. Its role in early and
      differential diagnosis].

PMID- 20694944
TI  - Preterm birth and adolescent bone mineral content.
AB  - The purpose of this study was to determine the influence of preterm low birth
      weight on bone mineral content in adolescence. In 2007 to 2008, data on
      adolescents were obtained for study, including 16 females and 25 males who were
      born preterm (<=37 weeks' gestation) between October 1, 1989, and December 31,
      1995, with a birth weight of less than 1850 g. Preterm low-birth-weight
      individuals were age- and sex-matched to full-term (>37 weeks) normal-birth
      weight (>2500 g) controls. Total body, hip, and spine bone mineral content (BMC)
      was assessed using dual energy X-ray absorptiometry. Male preterm individuals had
      less BMC at the proximal femur in adolescence compared with controls ( p < 0.05).
      However, once adjusted for age, maturity, height, weight, physical activity, and
      diet, there were no differences between groups ( p < 0.05) in any bone
      parameters. These findings suggest that preterm birth and low birth weight did
      not influence bone accrual in these individuals at adolescence.

PMID- 20694945
TI  - Guidelines of the German Respiratory Society for diagnosis and treatment of
      adults suffering from acute or chronic cough.
AB  - The first set of German guidelines for diagnosis and treatment of patients
      suffering from acute or chronic cough was published in 2004. Scientific
      developments over the past five years necessitate an update. The purpose of this
      document is to assist in ascertaining underlying causes and treating cough, in
      order to eliminate or minimize impairments of patients' health. The guidelines
      aim to introduce scientifically founded, evidence-based steps for the diagnosis
      and treatment of cough and optimize cost-effectiveness. Recommendations are
      assessed through the GRADE system (The Grades of Recommendation, Assessment,
      Development and Evaluation). Cough as a symptom is categorized as either acute
      (lasting up to 8 weeks) or chronic (lasting more than 8 weeks) and attributed to
      distinct diseases. For acute and chronic cough the diagnostic algorithms are
      updated; cost effectiveness is also taken into account. Additionally, the most
      frequent diagnostic errors are highlighted. Finally, available therapeutic
      options are discussed.

PMID- 20694947
TI  - Ethics and reproductive medicine. Preface.

PMID- 20694948
TI  - The value of diffusion-weighted MRI for prostate cancer detection and
      localization.
AB  - PURPOSE: The aim of this study was to evaluate the role of prebiopsy T2-weighted
      imaging (T2WI), quantitative diffusion-weighted imaging (DWI), and the
      combination of these magnetic resonance (MR) techniques (T2WI+DWI) in the
      detection and localization of peripheral zone prostate cancer. MATERIALS AND
      METHODS: T2WI and DWI (b value = 800 s/mm2) with an endorectal coil at 1.5 T were
      performed prospectively in 43 consecutive male patients with suspicion of
      prostate cancer before a systematic 12-core prostate biopsy. The peripheral zone
      of the prostate was evaluated after dividing it into sextants (n = 258). Minimum
      apparent diffusion coefficient (ADC) values of each sextant in the peripheral
      zone were measured. Two core biopsies were obtained from each sextant under
      transrectal ultrasound guidance. RESULTS: The mean minimum ADC values of the
      malignant sextants were significantly lower than that of noncancerous tissue,
      with a significant negative correlation between the ADC value and the Gleason
      score. The sensitivity, specificity, and area under the receiver operating
      characteristic curve for the detection and localization of prostate cancer within
      the peripheral zone were 71%, 77%, and 0.741 for T2WI alone; 84%, 82%, and 0.830
      for quantitative DWI alone; and 81%, 92%, and 0.863 for T2WI+DWI, respectively.
      The use of quantitative DWI, alone or combined with T2WI, improved diagnostic
      performance in prostate cancer detection and localization compared with T2WI
      alone (P = 0.020 and P = 0.001, respectively). CONCLUSION: Prebiopsy DWI is
      valuable in detecting, localizing, and grading prostate cancer within the
      peripheral zone, and the lowest ADC values can indicate the regions to be
      biopsied.

PMID- 20694950
TI  - Respiratory mucosal immunization with adenovirus gene transfer vector induces
      helper CD4 T cell-independent protective immunity.
AB  - BACKGROUND: Virus-vectored vaccine is a powerful activator of CD8 T cell-mediated
      immunity and is especially amenable to respiratory mucosal immunization, offering
      hopes for use in humans with diminished helper CD4 T cell function. However,
      whether virus-mediated mucosal immunization can produce immune protective CD8 T
      cells without the CD4 T cell help remains to be investigated. METHODS: We used a
      replication-deficient adenovirus vector expressing an Mycobacterium tuberculosis
      antigen Ag85A for intranasal vaccination and evaluated its effect on CD8 T cell
      activation and protection in mice depleted of CD4 T cells. RESULTS: Intranasal
      vaccination of CD4 T cell-depleted mice led to suboptimal generation of Ag
      specific tetramer(+) or interferon (IFN)-gamma-producing CD8 T cells in the lung
      and spleen but this was observed mainly at the early time after vaccination.
      Reduced CD8 T cell priming was also accompanied by decreased CD8 T cell responses
      (CTL). Nevertheless, the ratio of Ag-specific CD8 T cells to IFN-gamma-producing
      CD8 T cells in CD4 T cell-depleted hosts remained comparable to that in CD4 T
      cell-competent hosts. Furthermore, the 'unhelped' CD8 T cells also displayed a
      similar immune phenotype as the 'helped' counterparts. The animals with
      'unhelped' CD8 T cells were as well-protected from pulmonary M. tuberculosis
      challenge as those with 'helped' CD8 T cells in the absence of CD4 T cells.
      CONCLUSIONS: The data obtained in the present study suggest that the fully immune
      protective CD8 T cells can still be generated by respiratory mucosal viral
      mediated immunization without CD4 T cells and that CD8 T cells, 'helped' or
      'unhelped', can confer significant protection against pulmonary tuberculosis
      independent of CD4 T cells.

PMID- 20694951
TI  - Enhanced gene transfection with addition of a cell-penetrating peptide in
      substrate-mediated gene delivery.
AB  - BACKGROUND: To overcome extracellular barriers in gene therapy, controlled
      release technology has been adapted to protect DNA from degradation and maintain
      elevated DNA concentration. Although cell-penetrating peptides (CPPs) have been
      widely utilized to enhance the transfection efficiency of solution-based
      transfections, as far as we are aware, the effect of these peptides on substrate
      mediated transfection has not yet been reported. METHODS: In the present study,
      the effect of a CPP, KALA, on the substrate-mediated gene delivery was studied. A
      fast degrading cholic acid functionalized star poly((DL)-lactide) was used to
      fabricate Ca-P/DNA/KALA co-precipitates-deposited films and Ca-P/DNA/KALA co
      precipitates-encapsulated films for mediating substrate-mediated transfection.
      The in vitro gene transfections in HEK293T and HepG2 cells mediated by the
      different films were investigated. The effect of KALA content on gene
      transfection was studied. RESULTS: Gene expression of film-mediated transfections
      could be significantly enhanced by the addition of KALA at a quite low content
      with a DNA/KALA ratio of 10 : 1. As a result of the surface erosion mechanism of
      the functionalized star poly((DL)-lactide), our substrate-mediated transfection
      system could rapidly release Ca-P/DNA/KALA to mediate efficient gene expression.
      During the transfection, the degradation of the polymer films could be observed
      and the degradation did not show any unfavorable effects on gene expression.
      CONCLUSIONS: The presence of a CPP could significantly enhance the gene
      expression of substrate-mediated transfections.

PMID- 20694955
TI  - Health SWAps and external aid--a case study from Tajikistan.
AB  - As it moves from a relief to a development phase, the Republic of Tajikistan (RT)
      needs to attract more external aid and to ensure adequate alignment of this aid
      with health systems development priorities. A potential response to these two
      needs is a Sector-Wide Approach (SWAp), a method originating from post-colonial
      Africa and Asia that is increasingly being introduced in new contexts. However,
      little is known about whether SWAps are appropriate in the context of the former
      Soviet Union (FSU). This paper explores SWAps using Tajikistan as a case study. A
      number of lessons are identified for the Tajik health system, for other FSU
      countries and for health SWAps in general, covering issues of practical relevance
      to national and international health policy-makers.We conclude that context
      specific SWAps may be developed to suit Tajikistan, and other FSU countries.
      Tajikistan currently does not yet have all the key SWAp elements in place, but
      this should be seen as a motive for, rather than an impediment to, developing a
      SWAp. Other FSU countries have a more favourable environment for implementing
      health SWAps.

PMID- 20694956
TI  - Evaluation of the lipid-rich layer of reamer aspirate.
AB  - The fatty layer of aspirate obtained by reaming the femoral shaft using a
      reamer/irrigator/aspirator (RIA) device was characterized for fatty acid content
      and the presence of adult stem cells. Gas chromatography analysis was performed
      on samples taken from multiple patients to determine and compare the fatty acid
      contents of aspirate lipid samples. All four patients had the same four fatty
      acids present in the highest percentages: oleic, palmitic, linoleic and stearic.
      After successful isolation from bulk material, cells isolated from this lipid
      rich layer were studied to determine their osteogenic and growth potential on a
      clinically available ceramic bone graft substitute. The results of metabolic
      activity and intracellular protein assays indicated that the ceramics supported
      growth of the cells isolated from the aspirate fat layer, although levels of
      alkaline phosphatase (ALP) expression were low for cells grown on the ceramics.
      Cells will not transition along the osteogenic pathway when they are actively
      dividing, and active growth may have contributed to the lack of ALP expression in
      this study. Isolated cells grown on tissue culture plastic expressed significant
      levels of the bone marker ALP. The results of this study suggest that cells
      isolated from the fat layer of RIA aspirate proliferate on ceramic bone void
      filler and have the potential to differentiate along an osteogenic pathway.
      Previously considered waste, the lipid-rich fat layer of aspirate may be a source
      of mesenchymal stem cells that, either alone or in conjunction with currently
      available synthetic bone graft material, could be used to stimulate new bone
      growth.

PMID- 20694959
TI  - Distinguishing anxiety and depression in self-report: purification of the Beck
      Anxiety Inventory and Beck Depression Inventory-II.
AB  - The overlap of symptoms associated with anxiety and depressive disorders hinders
      their differentiation using self-report scales. The aim of this study was to
      develop purified versions of the Beck Anxiety Inventory (BAI) and the Beck
      Depression Inventory-II (BDI-II) that encompass only items highly specific to
      anxiety and depression, respectively. However, using these purified scales only
      increased the ability to differentiate anxiety and depressive disorders slightly.
      Anxiety and depression seem to be inherently linked and, thus, the high
      comorbidity of anxiety and depressive disorders seems to be not a function of the
      same types of symptoms being reported for each disorder. Nevertheless, purified
      BAI and BDI-II scales might be useful for separating the effects of interventions
      on anxiety and depressive symptoms.

PMID- 20694958
TI  - Generation of life events in bipolar spectrum disorders: a re-examination and
      extension of the stress generation theory.
AB  - The extent to which stress generation occurs in bipolar spectrum disorders (BSD)
      is not well understood. The present study examined whether 75 BSD participants
      experienced elevated rates of behavior-dependent life events, as compared with 38
      normal control participants. Within the BSD group, we also examined whether
      depressive or hypomanic symptoms prospectively predicted increases in various
      types of negative and positive life events. Results indicated that BSD
      participants experienced overall increases in behavior-dependent events over the
      follow-up, as compared with normal controls. At the symptom level, the event
      generation process occurred in more specific event domains. Results suggest that
      the stress generation theory of unipolar depression can be extended to BSD and
      that the type of generated events may be polarity-specific.

PMID- 20694960
TI  - Reasons for terminating psychotherapy: a general population study.
AB  - Clients' (N=693) reasons for ending psychotherapy and their associations with
      demographics, mental disorder caseness, and type of mental health care service
      provider were examined. The most frequently reported reason for termination was
      feeling better, however, a substantial minority of individuals reported
      terminating because of treatment dissatisfaction or wanting to solve problems
      independently. Lower income was associated with lower odds of termination because
      of feeling better and higher odds of termination because of a perception that
      therapy was not helping. Meeting criteria for an anxiety disorder, a mood
      disorder, or substance dependence decreased the odds of termination because of
      feeling better. These findings provide important information on the challenges to
      the successful completion of psychotherapy.

PMID- 20694961
TI  - Discrepancies between adolescent, mother, and father reports of adolescent
      internalizing symptom levels and their association with parent symptoms.
AB  - Discrepancies among informants on measures of internalizing symptoms in children
      and adolescents are common in the literature. One reason proposed for such
      discrepancies is that psychopathology may distort or bias third-party reports. In
      the present study, measures of adolescent internalizing symptom levels were
      completed by adolescents aged 13 to 18 years and their mothers and fathers.
      Parents also completed measures of their own depression, anxiety, and stress
      symptoms. Parent symptoms explained a small amount of variance in discrepancies
      between informants. Specifically, mothers' depression and stress symptoms were
      associated with discrepancies regarding sons' symptomatology and fathers' anxiety
      and stress symptoms were associated with discrepancies regarding daughters'
      symptomatology. Implications of informant discrepancies for both clinical
      practice and research are discussed.

PMID- 20694962
TI  - Depression Anxiety Stress Scale: is it valid for children and adolescents?
AB  - The Depression Anxiety Stress Scale (Lovibond & Lovibond, 1995) is used to assess
      the severity of symptoms in child and adolescent samples although its validity in
      these populations has not been demonstrated. The authors assessed the latent
      structure of the 21-item version of the scale in samples of 425 and 285 children
      and adolescents on two occasions, one year apart. On each occasion, parallel
      analyses suggested that only one component should be extracted, indicating that
      the test does not differentiate depression, anxiety, and stress in children and
      adolescents. The results provide additional evidence that adult models of
      depression do not describe the experience of depression in children and
      adolescents.

PMID- 20694963
TI  - The Youth Coping Responses Inventory: development and initial validation.
AB  - This study aimed to develop a comprehensive and representative measure of youths'
      dispositional coping. A sample of 450 youth, aged 10 to 16 years old, were
      recruited from public and private schools. The majority of the sample consisted
      of African American and Caucasian youth. After initial item generation, pilot
      testing, and item elimination, exploratory factor analyses resulted in a 44-item
      coping measure with a 3-factor solution (Diversion, Ameliorative Coping, and
      Destructive Coping). Internal consistency analyses indicated strong reliabilities
      (all coefficient alphas above .85) for the three scales and the composite score
      across races. Preliminary validity data confirmed that Diversion is the most
      adaptive coping factor and Destructive Coping the most maladaptive. These
      preliminary results indicate that the Youth Coping Responses Inventory presents a
      promising new measure of youths' coping.

PMID- 20694964
TI  - SSRI treatment during pregnancy: are we asking the right questions?

PMID- 20694965
TI  - Association of the serotonin transporter promoter region polymorphism with biased
      attention for negative word stimuli.
AB  - BACKGROUND: Biased attention for emotional stimuli reflects vulnerability or
      resilience to emotional disorders. The current study examines whether the 5
      HTTLPR polymorphism is associated with attentional biases for negative word
      stimuli. METHODS: Unmedicated, young adults with low current depression and
      anxiety symptoms (N=106) were genotyped for the 5-HTTLPR, including the single
      nucleotide polymorphism (SNP) rs25531 in the long allele of the 5-HTTLPR.
      Participants then completed a standard dot-probe task that measured attentional
      bias toward anxiety, dysphoric, and self-esteem words. RESULTS: The L(A)L(A)
      allele group demonstrated an attentional bias away from negative word stimuli.
      This attentional bias was absent among the S/L(G) carriers. CONCLUSIONS: These
      findings replicate previous work and suggest that 5-HTTLPR L(A) homozygotes
      possess a protective attentional bias that may decrease susceptibility to
      depression and anxiety.

PMID- 20694966
TI  - Impact of the HTR3A gene with early life trauma on emotional brain networks and
      depressed mood.
AB  - BACKGROUND: The risk for mental illnesses such as depression is increasingly
      conceptualized as the product of gene-environment interactions and their impact
      on brain structure and function. The role of serotonin 3A receptor gene (HTR3A 
      42C>T polymorphism) and its interaction with early life stress (ELS) was
      investigated in view of the receptor's localization to brain regions central to
      emotion processing. METHODS: Fronto-limbic grey matter (GM) loss was measured
      using magnetic resonance imaging and assessed using voxel-based morphometry
      analysis in 397 nonclinical individuals from the Brain Resource International
      Database. Negative mood symptoms were also assessed. RESULTS: The HTR3A CC
      genotype group, compared to the T carriers, demonstrated comparative loss to GM
      in hippocampal structures, which extended to the frontal cortices for those CC
      genotype individuals also exposed to ELS. Elevations in depressed mood were also
      evident. CONCLUSIONS: These findings suggest that the HTR3A CC genotype may be
      associated with alterations in brain structures central to emotion processing,
      particularly when exposed to stress, and further highlight the potential role of
      the serotonin system in the pathophysiology of affective disorders. In contrast,
      those individuals with the T allele, in particular the TT genotype, may be more
      protected from such alterations combined with minimal exposure to ELS events.

PMID- 20694967
TI  - Guidance of neurite outgrowth on aligned electrospun polypyrrole/poly(styrene
      beta-isobutylene-beta-styrene) fiber platforms.
AB  - The purpose of this work was to investigate the potential biomedical application
      of novel aligned electrospun polypyrrole (PPy)/poly(styrene-beta-isobutylene-beta
      styrene) (SIBS) fibers. After successfully aligning the electroactive PPy/SIBS
      fibers based on our modified electrospinning method, we demonstrated that neurite
      outgrowth from PC12 cells could be highly orientated parallel to the aligned
      PPy/SIBS fibers. Physical interactions between the nerve cells and PPy/SIBS
      fibers through filopodia "sensing" were observed using atomic force microscopy.
      These observations indicate a role of contact guidance as a mechanism for the
      observed alignment. This work highlights the capacity for electroactive PPy/SIBS
      fibers to support and guide nerve cell differentiation through topographic cues,
      which is a highly desirable characteristic in medical implants for neurological
      applications.

PMID- 20694968
TI  - The effect of anatase TiO2 nanotube layers on MC3T3-E1 preosteoblast adhesion,
      proliferation, and differentiation.
AB  - Titanium oxide nanotube layers by anodization have received considerable
      attention in biomedical application. Previous studies have demonstrated increased
      osteoblast (bone-forming cell) adhesion and function on nanotube layers compared
      with unanodized counterparts. More recently, one study showed amorphous TiO(2)
      nanotube diameter determined cell fate. The anatase phase is known to be much
      more beneficial for bone growth than amorphous phase, so there is increasing
      demand to explore the response of osteoblast on anatase phase TiO(2) nanotube
      layers. For this reason, we evaluated MC3T3-E1 preosteoblast behavior on
      different diameter nanotube layers with anatase phase. The results showed that
      the diameter of 20-70 nm provided an effective length scale for cell adhesion,
      alkaline phosphatase activity, and mineralization. However, cell adhesion,
      alkaline phosphatase activity, and mineralization were severely impaired on
      nanotube layers with 100-120 nm. Interestingly, the filopodia seemed not spread
      into the nanotubular and like extending anatase nanotube walls, where there may
      be higher numbers of atoms at the surface compared to the nanotubular
      architecture. To our surprise, the proliferation rates of cells cultured on
      anatase nanotube layers increased with increasing tube diameter from 20 to 120
      nm, which may be attributed to different length and nanometer-scale roughness of
      the nanotube layers.

PMID- 20694969
TI  - Enhanced osteoblastic activity and bone regeneration using surface-modified
      porous bioactive glass scaffolds.
AB  - The potential use as a bone substitute material of a three-dimensional bioactive
      glass fiber scaffold composed of Na(2)O-K(2)O-MgO-CaO-B(2)O(3)-P(2)O(5)-SiO(2)
      (BG1) was investigated in this work. Scaffolds were pre-treated with simulated
      body fluid (SBF) to promote the formation of two different bone-like apatite
      layers on their surfaces. The topography and roughness of the deposited layers
      were assessed by scanning electron microscopy (SEM), while the chemical
      composition and structure using X-ray photoelectron spectroscopy (XPS) and Raman
      spectroscopy, respectively. Based on surface analysis, the bioactive glass
      surfaces were ranked from smoothest to roughest: 0 SBF (untreated), 1x SBF and 2x
      SBF. A calcium-deficient carbonated hydroxyapatite (HCA) layer was present on
      both SBF-treated scaffolds, with higher number and larger bone-like apatite
      nodule formation in the 2x SBF case. MC3T3-E1 preosteoblasts showed a more
      flattened morphology and higher cell proliferation on the nontreated scaffolds;
      whereas, cells were more elongated and had higher osteoblastic activity on SBF
      treated samples. In vivo results in a rabbit calvarial bone defect model showed
      enhanced bone formation with SBF pretreated scaffolds, compared with untreated
      ones, commercially available Perioglass particles and empty defects. Our findings
      demonstrate that the formation of a rough HCA layer on bioactive glass porous
      scaffolds enhanced preosteoblast maturation in vitro, as well as bone formation
      in vivo.

PMID- 20694970
TI  - Carboxymethyl-chitin promotes chondrogenesis by inducing the production of growth
      factors from immune cells.
AB  - Many techniques have been tested for their ability to restore cartilage defects,
      but several problems still remain in the complete healing of injured cartilage.
      In our previous study, we found that a carboxymethyl-chitin/beta-tricalcium
      phosphate (CM-chitin/beta-TCP) composite induced cartilage regeneration in the
      osteochondral defects of rabbits in vivo. We also found that CM-chitin stimulated
      peritoneal exudate cells (PEC) in mice and induced several kinds of inflammatory
      cytokines and transforming growth factor beta-1 (TGF-beta1). In this study, we
      examined whether CM-chitin is responsible for the induction of chondrogenesis via
      the production of TGF-beta1 in vitro. The murine pluripotent cell line C3H10T1/2
      was maintained as a micromass culture in conditioned medium prepared from PEC
      stimulated with and without CM-chitin. CM-chitin-conditioned medium induced RNA
      expression of the chondrogenic-factor Sox9 and the matrix proteins aggrecan,
      Col2a1, and Comp. Their expression levels were decreased in the presence of anti
      TGF-beta1 antibody. The micromass tissues cultured in CM-chitin conditioned
      medium at day 21 were clearly stained by Toluidine blue or Alcian blue
      (histological staining) and collagen II antibody (immunohistological staining),
      showing the expression of acidic glycosaminoglycan and type II collagen. Similar
      results were observed in micromass tissue stimulated with TGF-beta1 as a positive
      control. However, no chondrogenesis occurred when CM-chitin was added directly to
      a C3H10T1/2 cell culture. These results indicated that CM-chitin is a potent
      inducer of chondrogenesis via the induction of TGF-beta1 in immune cells.

PMID- 20694971
TI  - Greater endothelial cell responses on submicron and nanometer rough titanium
      surfaces.
AB  - An in vitro competitive coculture system was designed in this study to
      investigate vascular cell functions on submicron (lateral feature sizes larger
      than 100 nm) and nanometer (lateral and vertical feature sizes smaller than 50
      nm) rough titanium surface features created via e-beam evaporation with identical
      chemistry to that of control (unmodified) titanium. Rat aortic endothelial cells
      (RAEC) and rat aortic smooth muscle cells (RASMC) were individually cultured and
      cocultured on such substrates for 4 h as well as 1, 3, and 5 days. In addition,
      RAEC and RASMC intracellular collagen and elastin synthesis were determined for
      up to 14 days on the various substrates. Compared to control flat titanium
      surfaces, the results showed for the first time that submicron rough surface
      features on titanium enhanced RAEC proliferation (followed by nanometer surface
      features), while simultaneously inhibiting RASMC proliferation. In addition,
      protein synthesis assays demonstrated enhanced collagen and elastin production by
      RAEC cultured on submicron rough titanium substrates (followed by nano rough)
      compared to control flat titanium substrates. Surface characterization results
      showed that submicron rough featured titanium possessed the greatest
      hydrophilicity (followed by nanometer surface featured), which may have promoted
      select protein adsorption to increase RAEC over RASMC function. In contrast to
      RASMC, RAEC morphology was significantly altered by the underlying titanium
      surface features, which may also explain the altered vascular cell functions on
      the different substrates. Thus, this study suggested that submicron to nanometer
      rough surface features should be further studied for improving titanium for
      vascular stent applications.

PMID- 20694972
TI  - Concentrated collagen-chondroitin sulfate scaffolds for tissue engineering
      applications.
AB  - Collagen-chondroitin sulfate biomaterial scaffolds have been used in a number of
      tissue-engineered products under development or in the clinics. In this article,
      we describe a new approach based on centrifugation for obtaining highly
      concentrated yet porous collagen scaffolds. Water uptake, chondroitin sulfate
      retention, morphology, mechanical properties, and tissue-engineering potential of
      the concentrated scaffolds were investigated. Our results show that the new
      approach can lead to scaffolds containing four times as much collagen as that in
      conventional unconcentrated scaffolds. Further, water uptake in the concentrated
      scaffolds was significantly greater while chondroitin sulfate retention in the
      concentrated scaffolds was unaffected. The value of mean pore diameter in the
      concentrated scaffolds was smaller than that in the unconcentrated scaffolds and
      the walls of the pores in the former comprised of a continuous sheet of collagen.
      The mechanical properties measured as moduli of elasticity in compression and
      tension were improved by as much as 30 times in the concentrated scaffolds. In
      addition, our tissue culture results with human mesenchymal stem cells and
      foreskin keratinocytes show that the new scaffolds can be used for cartilage and
      skin tissue-engineering applications.

PMID- 20694973
TI  - Combination of enzymes and flow perfusion conditions improves osteogenic
      differentiation of bone marrow stromal cells cultured upon starch/poly(epsilon
      caprolactone) fiber meshes.
AB  - Previous studies have shown that alpha-amylase and lipase are capable of
      enhancing the degradation of fiber meshes blends of starch and poly(epsilon
      caprolactone) (SPCL) under dynamic conditions, and consequently to promote the
      proliferation and osteogenic differentiation of bone marrow stromal cells (MSCs).
      This study investigated the effect of flow perfusion bioreactor culture in
      combination with enzymes on the osteogenic differentiation of MSCs. SPCL fiber
      meshes were seeded with MSCs and cultured with osteogenic medium supplemented
      with alpha-amylase, lipase, or a combination of the two for 8 or 16 days using
      static or flow conditions. Lipase and its combination with alpha-amylase enhanced
      cell proliferation after 16 days. In addition, the flow perfusion culture
      enhanced the infiltration of cells and facilitated greater distribution of
      extracellular matrix (ECM) throughout the scaffolds in the presence/absence of
      enzymes. A significant amount of calcium was detected after 16 days in all groups
      cultured in flow conditions compared with static cultures. Nevertheless, when
      alpha-amylase and lipase were included in the flow perfusion cultures, the
      calcium content was 379 +/- 30 microg/scaffold after as few as 8 days. The
      highest calcium content (1271 +/- 32 microg/scaffold) was obtained for SPCL/cell
      constructs cultured for 16 days in the presence of lipase and flow. Furthermore,
      von Kossa staining and tetracycline fluorescence of histological sections
      demonstrated mineral deposition within the scaffolds for all groups cultured for
      16 days under flow. However, all the data corroborate that lipase coupled with
      flow perfusion conditions improve the osteogenic differentiation of MSCs and
      enhance ECM mineralization.

PMID- 20694974
TI  - Comparison of morphology, orientation, and migration of tendon derived
      fibroblasts and bone marrow stromal cells on electrochemically aligned collagen
      constructs.
AB  - There are approximately 33 million injuries involving musculoskeletal tissues
      (including tendons and ligaments) every year in the United States. In certain
      cases the tendons and ligaments are damaged irreversibly and require replacements
      that possess the natural functional properties of these tissues. As a
      biomaterial, collagen has been a key ingredient in tissue engineering scaffolds.
      The application range of collagen in tissue engineering would be greatly
      broadened if the assembly process could be better controlled to facilitate the
      synthesis of dense, oriented tissue-like constructs. An electrochemical method
      has recently been developed in our laboratory to form highly oriented and densely
      packed collagen bundles with mechanical strength approaching that of tendons.
      However, there is limited information whether this electrochemically aligned
      collagen bundle (ELAC) presents advantages over randomly oriented bundles in
      terms of cell response. Therefore, the current study aimed to assess the
      biocompatibility of the collagen bundles in vitro, and compare tendon-derived
      fibroblasts (TDFs) and bone marrow stromal cells (MSCs) in terms of their ability
      to populate and migrate on the single and braided ELAC bundles. The results
      indicated that the ELAC was not cytotoxic; both cell types were able to populate
      and migrate on the ELAC bundles more efficiently than that observed for random
      collagen bundles. The braided ELAC constructs were efficiently populated by both
      TDFs and MSCs in vitro. Therefore, both TDFs and MSCs can be used with the ELAC
      bundles for tissue engineering purposes.

PMID- 20694975
TI  - Endothelialization of PVA/gelatin cryogels for vascular tissue engineering:
      effect of disturbed shear stress conditions.
AB  - Mechanically, poly(vinyl alcohol) (PVA)-based cryogels are extremely well suited
      for vascular tissue engineering applications. However, their surface properties
      lead to a slow rate of endothelialization, and the mode of cell attachment leaves
      the endothelium susceptible to removal under physiological shear stress
      conditions. In this study, abrupt and ramped disturbed shear stress conditions
      created by a turbulent orbital flow were used to examine endothelialization on
      PVA/gelatin cryogels. Cell proliferation rate and apoptosis were evaluated by
      fluorescent activated cell sorter (FACS) analysis, and the expression of cell
      adhesion molecules was used to evaluate the response of cells on cryogels to
      static and shear conditions by real-time polymerase chain reaction (RT-PCR).
      Application of a ramped shear stress had a profound effect on endothelial cell
      proliferation (22.30 +/- 0.20-fold increase), necrosis (eliminated), apoptosis
      (1.04 +/- 0.18 increase), and overall facilitation of endothelialization while
      concomitantly increasing nitric oxide (NO) synthesis levels. Ramped shear stress
      was also effective in helping the retention of the endothelial cells on the
      cryogel surface, whereas abrupt application caused widespread removal. Under
      static conditions, Selectin-P expression decreased, whereas both inter-cellular
      adhesion molecule (ICAM) and platelet endothelial cell adhesion molecule (PECAM)
      I expression increased on cryogels over a 10-day culture period. Under both shear
      stress conditions, Selectin-P expression was decreased both on cryogels and
      tissue culture polystyrene (TCPS). Controlled application of disturbed shear
      stress shortens endothelialization times on cryogel surfaces, in contrast to the
      established antiproliferative effect of shear stress caused by laminar flow,
      without compromising their functionality. This demonstrates how such mechanical
      stimuli can be exploited to alter cellular behavior and facilitate the required
      outcomes for tissue engineering applications.

PMID- 20694976
TI  - Surface nanoscale patterning of bioactive glass to support cellular growth and
      differentiation.
AB  - Bioactive glasses (BGs) have been widely used for bone tissue regeneration as
      they are able to bond directly with bone. Clinical applications of these
      materials are likely to be in particulate form. Nanoscale materials can mimic the
      surface properties of natural tissues, which have exhibited superior
      cytocompatible property and improved tissue regeneration. The objective of this
      study is to prepare bioactive glass particles with nanoscale or non-nanoscale
      surface features and investigate their microstructure, apatite-forming
      bioactivity and cellular response. The microstructure and micro-nanoscale surface
      morphology were controlled by adding a hydroxyl-carboxyl acid (citric acid) in
      the sol-gel process. Results shown that the addition of citric acid induced the
      formation of nanoscale surface structure and increased the specific surface area,
      pore volume and pore size of bioactive glass particles. The citric acid with low
      concentration-derived sol-gel bioactive glasses (CBGs) resulted in an enhanced
      apatite-formation ability in simulated body fluids (SBF) compared to normal
      bioactive glasses. The attachment and proliferation of rat marrow mesenchymal
      stem cells (RMSCs) on CBGs (low concentration) were higher than those of normal
      BGs, demonstrating that the CBGs had the excellent cytocompatibility. RMSCs on
      CBGs (low concentration) expressed the higher alkaline phosphatase activity (ALP)
      than normal BGs and tissue culture plastic, revealing that CBGs can induced
      differentiation of RMSCs to the osteogenic lineage. Such improved physical and
      biological properties of CBGs (low concentration) should be useful in developing
      new bioactive glass materials for stem cell-based bone regeneration or biomimic
      tissue engineering scaffolds.

PMID- 20694978
TI  - Statistical approach of chemistry and topography effect on human osteoblast
      adhesion.
AB  - Our objective in this work was to determine statistically the relative influence
      of surface topography and surface chemistry of metallic substrates on long-term
      adhesion of human bone cell quantified by the adhesion power (AP). Pure titanium,
      titanium alloy, and stainless steel substrates were processed with electro
      erosion, sandblasting, or polishing giving various morphologies and amplitudes.
      The surface chemistry was characterized by X-ray photoelectron spectroscopy (XPS)
      associated with an extensive analysis of surface topography. The statistical
      analysis demonstrated that the effect on AP of the material composition was not
      significant. More, no correlation was found between AP and the surface element
      concentrations determined by XPS demonstrating that the surface chemistry was not
      an influencing parameter for long-term adhesion. In the same way, the roughness
      amplitude, independently of the process, had no influence on AP, meaning that
      roughness amplitude is not an intrinsic parameter of long-term adhesion. On the
      contrary, the elaboration process alone had a significant effect on AP. For a
      same surface elaboration process, the number of inflexion points, or G parameter,
      was the most pertinent roughness parameter for describing the topography
      influence on long-term adhesion. Thus, more the inflexion points, more the
      discontinuities, higher the long-term adhesion.

PMID- 20694977
TI  - Fabrication of cardiac patch with decellularized porcine myocardial scaffold and
      bone marrow mononuclear cells.
AB  - Tissue engineered cardiac grafts are a promising therapeutic mode for ventricular
      wall reconstruction. Recently, it has been found that acellular tissue scaffolds
      provide natural ultrastructural, mechanical, and compositional cues for
      recellularization and tissue remodeling. We thus assess the potential of
      decellularized porcine myocardium as a scaffold for thick cardiac patch tissue
      engineering. Myocardial sections with 2-mm thickness were decellularized using
      0.1% sodium dodecyl sulfate and then reseeded with differentiated bone marrow
      mononuclear cells. We found that thorough decellularization could be achieved
      after 2.5 weeks of treatment. Reseeded cells were found to infiltrate and
      proliferate in the tissue constructs. Immunohistological staining studies showed
      that the reseeded cells maintained cardiomyocyte-like phenotype and possible
      endothelialization was found in locations close to vasculature channels,
      indicating angiogenesis potential. Both biaxial and uniaxial mechanical testing
      showed a stiffer mechanical response of the acellular myocardial scaffolds;
      however, tissue extensibility and tensile modulus were found to recover in the
      constructs along with the culture time, as expected from increased cellular
      content. The cardiac patch that we envision for clinical application will benefit
      from the natural architecture of myocardial extracellular matrix, which has the
      potential to promote stem cell differentiation, cardiac regeneration, and
      angiogenesis.

PMID- 20694979
TI  - Behavior of human chondrocytes in engineered porous bacterial cellulose
      scaffolds.
AB  - Regeneration of articular cartilage damage is an area of great interest due to
      the limited ability of cartilage to self-repair. The latest cartilage repair
      strategies are dependent on access to biomaterials to which chondrocytes can
      attach and in which they can migrate and proliferate, producing their own
      extracellular matrix. In the present study, engineered porous bacterial cellulose
      (BC) scaffolds were prepared by fermentation of Acetobacter xylinum (A. xylinum)
      in the presence of slightly fused wax particles with a diameter of 150-300
      microm, which were then removed by extrusion. This porous material was evaluated
      as a scaffold for cartilage regeneration. Articular chondrocytes from young adult
      patients as well as neonatal articular chondrocytes were seeded with various
      seeding techniques onto the porous BC scaffolds. Scanning electron microscopy
      (SEM) analysis and confocal microscopy analysis showed that cells entered the
      pores of the scaffolds and that they increasingly filled out the pores over time.
      Furthermore, DNA analysis implied that the chondrocytes proliferated within the
      porous BC. Alcian blue van Gieson staining revealed glycosaminoglycan (GAG)
      production by chondrocytes in areas where cells were clustered together. With
      some further development, this novel biomaterial can be a suitable candidate for
      cartilage regeneration applications.

PMID- 20694980
TI  - Synthesis, in vitro macrophage response and detoxification of bamboo charcoal
      beads for purifying blood.
AB  - Bamboo charcoal beads (BCBs) were formed by coprecipitating bamboo charcoal
      particles with chitosan in alkaline solution. The amount of chitosan in the BCBs
      and their surface properties were measured. When 13-52 mg BCBs were exposed to
      RAW 264.7 macrophages, the amount of nitric oxide released and the cell viability
      were close to those of the blank. The amount of cytokine IL-6 secreted by
      macrophages did not depend on the dose of BCBs but macrophages secreted more TNF
      alpha in response to higher doses of BCBs. However, the cytokine levels were
      relatively low, suggesting the favorable biocompatibility of BCBs. In adsorption
      experiments, BCBs adsorbed and released bovine serum albumin at particular
      concentrations, whereas BCBs adsorbed L-phenylalanine without a sign of release.
      This difference is attributed to the hydrophilicity and the pore size of the
      BCBs. Finally, the potential of BCBs as biocompatible adsorbents in blood
      detoxification is considered.

PMID- 20694981
TI  - Fabrication and in vitro and in vivo cell infiltration study of a bilayered
      cryogenic electrospun poly(D,L-lactide) scaffold.
AB  - Cryogenic electrospinning has previously been demonstrated for controlling the
      pore sizes of electrospun scaffolds, which has been impossible with traditional
      electrospinning processes. This article describes the application of the
      cryogenic technique to fabricate a bilayered electrospun poly(D,L-lactide)
      scaffold (BLES) in a single uninterrupted process. The resulting BLES consisted
      of a traditional electrospun (ES) fibrous layer with a dense pore area of 17 +/-
      3 microm(2) adjacent to a cryogenic electrospun layer (CES) with a pore area of
      3300 +/- 500 microm(2). The significance of this bilayered scaffold was to mimic
      the anatomical structure of tissues with dense basement membrane followed by
      loose and highly porous connective tissue such as skin and blood vessels. Cell
      infiltration in the BLES was compared in vitro and in vivo. Both studies
      suggested the CES supported high cell infiltration, whereas the ES could serve as
      a physical barrier to prevent cell infiltration across the CES-ES boundary
      because of its size exclusion. The bilayered structure produced by this technique
      suggests a great potential for engineering tissues with similar architectures.

PMID- 20694982
TI  - Role of mesenchymal stem cells in tissue engineering of meniscus.
AB  - Tissue engineering is a promising approach for the treatment of tissue defects.
      Mesenchymal stem cells are of potential use as a source of repair cells or of
      important growth factors for tissue engineering. The purpose of this study was to
      examine the role of mesenchymal stem cells in meniscal tissue repair. This was
      tested using several cell and biomaterial-based treatment options for repair of
      defects in the avascular zone of rabbit menisci. Circular meniscal punch defects
      (2 mm) were created in the avascular zone of rabbit menisci and left empty or
      filled with hyaluronan-collagen composite matrices without cells, loaded with
      platelet-rich plasma, autologous bone marrow, or autologous mesenchymal stem
      cells. In some experiments, matrices with stem cells were precultured in
      chondrogenic medium for 14 days before implantation. Rabbits were then allowed
      free cage movement after surgery for up to 12 weeks. Untreated defects and
      defects treated with cell-free implants had muted fibrous healing responses.
      Neither bone marrow nor platelet-rich plasma loaded in matrices produced
      improvement in healing compared with cell-free implants. The implantation of 14
      days precultured chondrogenic stem cell-matrix constructs resulted in
      fibrocartilage-like repair tissue, which was only partially integrated with the
      native meniscus. Non-precultured mesenchymal stem cells in hyaluronan-collagen
      composite matrices stimulated the development of completely integrated meniscus
      like repair tissue. The study shows the necessity of mesenchymal stem cells for
      the repair of meniscal defects in the avascular zone. Mesenchymal stem cells seem
      to fulfill additional repair qualities besides the delivery of growth factors.

PMID- 20694983
TI  - Effect of macromer weight percent on neural cell growth in 2D and 3D
      nondegradable PEG hydrogel culture.
AB  - Neural precursor cells (NPCs) are a renewable cell source that may be useful for
      neural cell transplant therapies. Their expansion and differentiation potential
      have traditionally been explored by culturing them on stiff tissue culture
      polystyrene. Here we describe advantages of an alternative culture system: bio
      inert poly(ethylene glycol) (PEG) hydrogels. Specifically this work reports the
      effect that macromer weight percent has on the metabolic and apoptotic activity,
      proliferation, and cellular composition of a mixed population of neurons and
      multipotent NPCs grown both on 2D and within 3D PEG hydrogels. In 2D culture,
      hydrogel properties did not affect metabolic or apoptotic activity but did impact
      cell proliferation and composition leading to an increase in glial cell
      reactivity as stiffness increased. In 3D culture, low weight percent hydrogels
      led to greater metabolic activity and lower apoptotic activity with significant
      proliferation observed only in hydrogels that closely matched the stiffness of
      native brain tissue. PEG hydrogels therefore provide a versatile in vitro culture
      system that can be used to culture and expand a variety of neural and glial cell
      types simply by altering the material properties of the hydrogel.

PMID- 20694984
TI  - Epidermal and dermal integration into sphere-templated porous poly(2-hydroxyethyl
      methacrylate) implants in mice.
AB  - Percutaneous medical devices remain susceptible to infection and failure. We
      hypothesize that healing of the skin into the percutaneous device will provide a
      seal, preventing bacterial attachment, biofilm formation, and subsequent device
      failure. Porous poly(2-hydroxyethyl methacrylate) [poly(HEMA)] with sphere
      templated pores (40 microm) and interconnecting throats (16 microm) were
      implanted in normal C57BL/6 mice for 7, 14, and 28 days. Poly(HEMA) was either
      untreated, keeping the surface nonadhesive for cells and proteins, or modified
      with carbonyldiimidazole (CDI) or CDI reacted with laminin 332 to enhance
      adhesion. No clinical signs of infection were observed. Epidermal and dermal
      response within the poly(HEMA) pores was evaluated using light and transmission
      electron microscopy. Cells (keratinocytes, fibroblasts, endothelial cells,
      inflammatory cells) and basement membrane proteins (laminin 332, beta4 integrin,
      type VII collagen) could be demonstrated within the poly(HEMA) pores of all
      implants. Blood vessels and dermal collagen bundles were evident in all of the 14
      and 28-day implants. Fibrous capsule formation and permigration were not
      observed. Sphere-templated polymers with 40 microm pores demonstrate an ability
      to recapitulate key elements of both the dermal and the epidermal layers of skin.
      Our morphological findings indicate that the implant model can be used to study
      the effects of biomaterial pore size, pore interconnect (throat) size, and
      surface treatments on cutaneous biointegration. Further, this model may be used
      for bacterial challenge studies.

PMID- 20694985
TI  - Bone regeneration by bioactive hybrid membrane containing FGF2 within rat
      calvarium.
AB  - This study examined the bone regeneration potential of a novel hybrid membrane
      consisting of collagen and nano-bioactive glass (nBG) incorporating basic
      fibroblast growth factor (FGF2) for use in guided bone regeneration. nBG was
      added to a reconstitution of collagen at a concentration of 30%, and the hybrid
      was formulated into a thin membrane. FGF2 (50 microg/ml) was adsorbed to the
      hybrid membrane. This level of FGF2 was found to be the optimal concentration to
      stimulate osteoblastic differentiation in vitro. Three membrane groups, including
      pure collagen, collagen-nBG hybrid and its combination with FGF2 were implanted
      within a rat calvarium defect (phi = 5 mm) for a period of 3 weeks.
      Histomorphometric analysis was carried out to evaluate the bone regeneration
      within the defect. The results showed that the defect in the collagen-nBG-FGF2
      membrane was recovered almost completely, while partial recovery was observed in
      the other membrane groups (collagen and collagen-BG). However, there was little
      defect recovery in the blank control. The new bone formation was as high as
      approximately 60, approximately 45, and approximately 30% of the defect treated
      with the collagen-nBG-FGF2, collagen-BG, and collagen, respectively, whilst only
      4% of new bone was observed in the blank control. Overall, the nBG was shown to
      stimulate bone formation of the collagen membrane, and FGF2 synergistically
      accelerated the bone regeneration within a rat calvarium defect.

PMID- 20694986
TI  - Electrospun scaffold topography affects endothelial cell proliferation, metabolic
      activity, and morphology.
AB  - A family of methacrylic terpolymer biomaterials was electrospun into three
      dimensional fibrous scaffolds. The glass transition temperature of the polymer
      correlates with the morphology of the resulting scaffold. Glassy materials
      produce scaffolds with discrete fibers and a high percent void space (84%) while
      the rubbery materials produced scaffolds with fused fibers and a much lower
      percent void space (18%). By electrospinning onto a rotating mandrel, aligned
      fiber scaffolds were fabricated, and it was shown that controlling the rotation
      speed of the collector allowed for control over the degree of fiber alignment.
      The electrospinning was shown to not degrade the number average molecular weight
      of the polymer chains. Human umbilical vein endothelial cells (HUVECs) were
      seeded onto the electrospun scaffolds under static conditions and it was found
      that the morphology of the scaffold controlled the cellular proliferation, the
      metabolic activity, and the morphology of adherent cells. In particular, HUVECs
      seeded onto low void space scaffolds exhibited enhanced cellular spreading,
      enzymatic activity, and proliferation. HUVECs seeded onto aligned fiber scaffolds
      did not demonstrate increased proliferation; however, the cells did organize
      themselves in the direction of fiber alignment resulting in cells with elongated
      morphology.

PMID- 20694987
TI  - Bladder tissue engineering: tissue regeneration and neovascularization of HA-VEGF
      incorporated bladder acellular constructs in mouse and porcine animal models.
AB  - Successful tissue engineering requires appropriate recellularization and
      vascularization. Herein, we assessed the regenerative and angiogenic effects of
      porcine bladder acellular matrix (ACM) incorporated with hyaluronic acid (HA) and
      vascular endothelial growth factor (VEGF) in mouse and porcine models. Prepared
      HA-ACMs were rehydrated in different concentrations of VEGF (1, 2, 3, 10, and 50
      ng/g ACM). Grafts were implanted in mice peritoneum in situ for 1 week.
      Angiogenesis was quantified with CD31 and Factor VIII immunostaining using Simple
      PCI. Selected optimal VEGF concentration that induced maximum vascularization was
      then used in porcine bladder augmentation model. Implants were left in for 4 and
      10 weeks. Three groups of six pigs each were implanted with ACM alone, HA-ACM,
      and HA-VEGF-ACM. Histological, immunohistochemical (Uroplakin III, alpha-SMA,
      Factor VIII), and immunofluorescence (CD31) analysis were performed to assess
      graft regenerative capacity and angiogenesis. In mouse model, statistically
      significant increase in microvascular density was demonstrated in the 2 ng/g ACM
      group. When this concentration was used in porcine model, recellularization
      increased significantly from weeks 4 to 10 in HA-VEGF-ACM, with progressive
      decrease in fibrosis. Significantly increased vascularization, coupled with
      increased urothelium and smooth muscle cell (SMC) regeneration, was observed in
      HA-VEGF grafts at week 10 in the center and periphery, compared with week 4. HA
      VEGF grafts displayed highest in vivo epithelialization, neovascularization, and
      SMCs regeneration. A total of 2 ng/g tissue VEGF when incorporated with HA proved
      effective in stimulating robust graft recellularization and vascularization,
      coordinated with increased urothelial bladder development and SMC augmentation
      into bundles by week 10.

PMID- 20694988
TI  - In vitro biological evaluation of electrospun cellulose acetate fiber mats
      containing asiaticoside or curcumin.
AB  - Ultra-fine cellulose acetate (CA; M(w) approximately 30,000 Da; degree of acetyl
      substitution approximately 2.4) fiber mats containing either asiaticoside [from
      the plant Centella asiatica (L.); either in the form of a crude extract (CACE) or
      pure substance (PAC)] or curcumin (CM; from the plant Curcuma longa L.) were
      successfully prepared. The proposed use of these materials is as
      topical/transdermal patches or wound dressings. Here, the potential for use of
      these herb-loaded CA fiber mats as wound dressings was evaluated in terms of the
      stability and the antioxidant activity of the as-loaded herbal substances, the
      ability to support both the attachment and the proliferation of fibroblasts and
      the ability of the cultured fibroblasts to synthesize collagen. Normal human
      dermal fibroblasts (NHDF) were used as the reference fibroblastic cells. The
      results showed that the as-loaded herbal substances were stable even after the
      herb-loaded CA fiber mats had been aged either at room temperature or at 40
      degrees C for a period of up to 4 months. The inclusion of asiaticoside [either
      2% (w/w) CACE or 40% (w/w) PAC] rendered the resulting CA fiber mats their
      superiority in supporting the attachment, promoting the proliferation, and
      upregulating the production of collagen of the seeded and/or the cultured NHDF to
      the corresponding solvent-cast films and the neat CA fiber mats. On the other
      hand, the presence of CM imparted the antioxidant activity to the resulting CA
      fiber mats.

PMID- 20694989
TI  - Bioactivation of porous polyurethane scaffolds using fluorinated RGD surface
      modifiers.
AB  - Biomaterial scaffolds for tissue engineering require appropriate cell adhesion,
      proliferation, and infiltration into their three-dimensional (3D) porous
      structures. Surface modification techniques have the potential to enhance cell
      infiltration into synthetic scaffolds while retaining bulk material properties
      intact. The objective of this work was to assess the potential of achieving a
      uniform surface modification in 3D porous constructs through the blending of
      surface-modifying additives known as bioactive fluorinated surface modifiers
      (BFSMs) with a base polyurethane material. By coupling RGD peptides to the
      fluorinated surface modifiers to form RGD-BFSMs, the BFSMs can act as a vehicle
      for the delivery of RGD moieties to the surface without direct covalent
      attachment to the polymer substrate. Fluorescent RGD-BFSMs were shown to migrate
      to the polymer-air interfaces within the porous scaffolds by two-photon confocal
      microscopy. A-10 rat aortic smooth muscle cells were cultured for 4 weeks on
      nonmodified and RGD-BFSM-modified porous scaffolds, and cell adhesion,
      proliferation, and viability were quantified at different depths. RGD-BFSM
      modified scaffolds showed significantly greater cell numbers within deeper
      regions of the scaffolds, and this difference became more pronounced over time.
      This study demonstrates an effective approach to promote cell adhesion and
      infiltration within thick (approximately 0.5 cm) porous synthetic scaffolds by
      providing a uniform distribution of adhesive peptide throughout the scaffolds
      without the use of covalent surface reaction chemistry.

PMID- 20694990
TI  - Tailoring the degradation kinetics of mesoporous silicon structures through
      PEGylation.
AB  - Injectable and implantable porosified silicon (pSi) carriers and devices for
      prolonged and controlled delivery of biotherapeutics offer great promise for
      treatment of various chronic ailments and acute conditions. Polyethylene glycols
      (PEGs) are important surface modifiers currently used in clinic mostly to avoid
      uptake of particulates by reticulo-endothelial system (RES). In this work we show
      for the first time that covalent attachment of PEGs to the pSi surface can be
      used as a means to tune degradation kinetics of silicon structures. Seven PEGs
      with varying molecular weights (245, 333, 509, 686, 1214, 3400, and 5000 Da) were
      employed and the degradation of PEGylated pSi hemispherical microparticles in
      simulated physiological conditions was monitored by means of ICP-AES, SEM, and
      fluorimetry. Biocompatibility of the systems with human macrophages in vitro was
      also evaluated. The results clearly indicate that controlled PEGylation of
      silicon microparticles can offer a sensitive tool to finely tune their
      degradation kinetics and that the systems do not induce release of
      proinflammatory cytokines IL-6 and IL-8 in THP1 human macrophages.

PMID- 20694991
TI  - Primary human osteoblast culture on 3D porous collagen-hydroxyapatite scaffolds.
AB  - There is a need in tissue-engineering for 3D scaffolds that mimic the natural
      extracellular matrix of bone to enhance cell adhesion, proliferation, and
      differentiation. The scaffold is also required to be degradable. A highly porous
      scaffold has been developed to incorporate two of the extracellular components
      found in bone-collagen and hydroxyapatite (HA). The scaffold's collagen component
      is an afibrillar monomeric type I atelocollagen extracted from foetal calf's
      skin. This provided a novel environment for the inclusion of HA powder. Five
      hundred thousand primary human osteoblasts were seeded onto 4 mm cubed scaffolds
      that varied in ratio of HA to collagen. Weight ratios of 1:99, 25:75, 50:50, and
      75:25 hydroxyapatite:collagen (HA:Collagen) were analysed. The scaffolds plus
      cells were cultured for 21 days. DNA assays and live/dead viability staining
      demonstrated that all of the scaffolds supported cell proliferation and
      viability. An alkaline phosphatase assay showed similar osteoblast phenotype
      maintenance on all of the 3D scaffolds analysed at 21 days. MicroCT analysis
      demonstrated an increase in total sample volume (correlating to increase in
      unmineralised matrix production). An even distribution of HA throughout the
      collagen matrix was observed using this technique. Also at 3 weeks, reductions in
      the percentage of the mineralised phase of the constructs were seen. These
      results indicate that each of the ratios of HA/collagen scaffolds have great
      potential for bone tissue engineering.

PMID- 20694992
TI  - Corrosion resistance and in vitro response of laser-deposited Ti-Nb-Zr-Ta alloys
      for orthopedic implant applications.
AB  - While direct metal deposition of metallic powders, via laser deposition, to form
      near-net shape orthopedic implants is an upcoming and highly promising
      technology, the corrosion resistance and biocompatibility of such novel metallic
      biomaterials is relatively unknown and warrants careful investigation. This
      article presents the results of some initial studies on the corrosion resistance
      and in vitro response of laser-deposited Ti-Nb-Zr-Ta alloys. These new generation
      beta titanium alloys are promising due to their low elastic modulus as well as
      due the fact that they comprise of completely biocompatible alloying elements.
      The results indicate that the corrosion resistance of these laser-deposited
      alloys is comparable and in some cases even better than the currently used
      commercially-pure (CP) titanium (Grade 2) and Ti-6Al-4V ELI alloys. The in vitro
      studies indicate that the Ti-Nb-Zr-Ta alloys exhibit comparable cell
      proliferation but enhanced cell differentiation properties as compared with Ti
      6Al-4V ELI.

PMID- 20694993
TI  - The effect of the association of near infrared laser therapy, bone morphogenetic
      proteins, and guided bone regeneration on tibial fractures treated with internal
      rigid fixation: a Raman spectroscopic study.
AB  - Fractures have different etiology and treatment and may be associated or not to
      bone losses. Laser light has been shown to improve bone healing. We aimed to
      assess, through Raman spectroscopy, the level of CHA (approximately 958 cm(-1))
      on complete fractures animals treated with IRF treated or not with Low Level
      Laser Therapy-LLLT and associated or not to BMPs and GBR. Complete tibial
      fractures were created on 15 animals that were divided into five groups. LLLT
      (Laser Unit, Kondortech, Sao Carlos, SP, Brazil, lambda790 nm, 4 J/cm(2)/point,
      40 mW, phi approximately 0.5 cm(2), 16 J/cm(2) session) started immediately after
      surgery and repeated at 48 h interval (2 weeks). Animal death occurred after 30
      days. Raman spectroscopy was performed at the surface of the fracture. Our
      results showed significant differences between the groups IRF + BL /IRF_NBL (p =
      0.05); between all experimental groups and untreated bone; bone/IRF + BL; IRF +
      BL + Bio + GBR; IRF + BL + LLLT; IRF + BL + Bio + GBR + LLLT; IRF_NBL (p < 0.001,
      all); IRF_NBL/IRF + BL + LLLT (p = 0.03); IRF_NBL/IRF + BL + Bio + GBR + LLLT (p
      = 0.02); IRF + BL/IRF + BL + LLLT (p = 0.04); IRF + BL/IRF + BL + Bio + GBR +
      LLLT (p = 0.002); IRF + BL + Bio + GBR/IRF + BL + Bio + GBR + LLLT (p = 0.05). It
      is concluded that the use of NIR LLLT associated to BMPs and GBR was effective in
      improving bone healing on fractured bones due to increased levels of CHA.

PMID- 20694994
TI  - Effects of orthopedic polymer particles on chemotaxis of macrophages and
      mesenchymal stem cells.
AB  - Wear particles generated from total joint arthroplasty (TJA) stimulate
      macrophages to release chemokines. The role of chemokines released from wear
      particle-stimulated macrophages on the migration of macrophages and
      osteoprogenitor cells in vitro has not been elucidated. In this study, we
      challenged murine macrophages (RAW 264.7) with clinically relevant polymethyl
      methacrylate (PMMA, 1-10 microm) and ultra high molecular weight polyethylene
      (UHMWPE, 2-3 microm) particles. The chemotactic effects of the conditioned media
      (CM) were tested in vitro using human macrophages (THP-1) and human mesenchymal
      stem cells (MSCs) as the migrating cells. CM collected from both particle types
      had a chemotactic effect on human macrophages, which could be eliminated by
      monocyte chemotactic protein-1 (MCP-1) neutralizing antibody. Blocking the CCR1
      receptor eliminated the chemotactic effect, while CCR2 antibody only partially
      decreased THP-1 cell migration. CM from PMMA but not UHMWPE-exposed macrophages
      led to chemotaxis of MSCs; this effect could be eliminated by macrophage
      inflammatory protein-1 alpha (MIP-1alpha) neutralizing antibody. Neither CCR1 nor
      CCR2 blocking antibodies showed an effect on the migration of MSCs. Chemokines
      released by macrophages stimulated by wear particles can have an effect on the
      migration of macrophages and MSCs. This effect seems to be dependent on the
      particle type, and may be modulated by MCP-1 and MIP-1alpha, however, more than
      one chemokine may be necessary for chemotaxis.

PMID- 20694995
TI  - Aligned poly(L-lactic-co-e-caprolactone) electrospun microfibers and knitted
      structure: a novel composite scaffold for ligament tissue engineering.
AB  - We developed a novel technique involving knitting and electrospinning to
      fabricate a composite scaffold for ligament tissue engineering. Knitted
      structures were coated with poly(L-lactic-co-e-caprolactone) (PLCL) and then
      placed onto a rotating cylinder and a PLCL solution was electrospun onto the
      structure. Highly aligned 2-microm-diameter microfibers covered the space between
      the stitches and adhered to the knitted scaffolds. The stress-strain tensile
      curves exhibited an initial toe region similar to the tensile behavior of
      ligaments. Composite scaffolds had an elastic modulus (150 +/- 14 MPa) similar to
      the modulus of human ligaments. Biological evaluation showed that cells
      proliferated on the composite scaffolds and they spontaneously orientated along
      the direction of microfiber alignment. The microfiber architecture also induced a
      high level of extracellular matrix secretion, which was characterized by
      immunostaining. We found that cells produced collagen type I and type III, two
      main components found in ligaments. After 14 days of culture, collagen type III
      started to form a fibrous network. We fabricated a composite scaffold having the
      mechanical properties of the knitted structure and the morphological properties
      of the aligned microfibers. It is difficult to seed a highly macroporous
      structure with cells, however the technique we developed enabled an easy cell
      seeding due to presence of the microfiber layer. Therefore, these scaffolds
      presented attractive properties for a future use in bioreactors for ligament
      tissue engineering.

PMID- 20694996
TI  - Oriented immobilization of anti-CD34 antibody on titanium surface for self
      endothelialization induction.
AB  - Inducing spontaneous endothelialization of synthetic cardiovascular implant in
      vivo is thought to be a promising approach to solve the surface-induced
      thrombosis and restenosis problem. In the present study, anti-CD34 antibody, a
      kind of special marker of EPC, was oriented immobilized on titanium surface by
      means of a layer-by-layer self-assembly coating technique. The multilayer coating
      was prepared by first depositing one layer of avidin on the NaOH-treated titanium
      substrate, then depositing a layer of biotinylated protein A binding to the
      avidin, and finally anti-CD34 antibody was oriented immobilized by protein A
      binding to the Fc fragment (COOH-terminal of a antibody molecule, which has no
      antigen binding sites) of the anti-CD34 antibody with its antigen binding
      fragment (Fab) away from the titanium surface. The coated titanium was exposed to
      EPC derived from mouse bone marrow in vitro, and implanted into dog femoral
      arteries. The results suggested that the anti-CD34 antibody immobilized surfaces
      could increase EPC attachment and capture, and induce rapid complete
      endothelialization of the lumenal surface of the implant in vivo. It suggests
      that the approach described here may be used for fabrication of titanium-based
      vascular implant surfaces for inducing endothelialization in vivo.

PMID- 20694997
TI  - Design and characterization of PEGylated terpolymer biomaterials.
AB  - A terpolymer copolymerized from hexyl methacrylate, methyl methacrylate, and
      poly(ethylene glycol) methacrylate (PEGMA) was synthesized. Polymers containing 0
      25 mol % PEGMA were studied. As the mole fraction of PEGMA in the polymer chains
      increased, the material becomes more hydrophilic as observed by a decrease in the
      contact angle of water (81 degrees -68 degrees) and an increase in the
      equilibrium water absorption (0.7-237 wt %). Furthermore, the material shows
      nonfouling interfacial properties through resistance to protein adsorption and
      cellular attachment. A total of 1.2 microg/cm(2) fibrinogen, 18,000 HUVECs/cm(2),
      and 3,000,000 platelets/cm(2) adsorbed or adhered on non-PEGylated materials,
      whereas very low amounts of protein or cells were observed on materials
      containing >or=15 mol % PEGMA. Being thermoplastic, the polymer can be processed
      postsynthesis. To illustrate the processing capabilities of the material, polymer
      solutions were electrospun into nonwoven fibrous scaffold, which also retained
      their nonfouling character.

PMID- 20694998
TI  - Cryogenic prototyping of chitosan scaffolds with controlled micro and macro
      architecture and their effect on in vivo neo-vascularization and cellular
      infiltration.
AB  - A major challenge in tissue engineering has been to develop scaffolds with
      controlled complex geometries, on both the macro- and micro-scale. One group of
      techniques, using rapid prototyping (RP) processes, has the capability to produce
      complex three-dimensional structures with good control over the size, geometry,
      and connectivity of the pores. In this article, a novel technique based on RP
      technology, that is, cryogenic prototyping (CP), that has the capability to
      fabricate scaffolds with controlled macro- and micro-structures, is presented.
      Our in vivo studies showed that the micro architecture (i.e., both pore size and
      pore orientation) and macro structures of the CP scaffolds affect both cellular
      infiltration and neo-vascularization. Full cellular infiltration and neo
      vascularization were observed after 28 days in scaffolds with micropore sizes of
      90 microm. In addition, it was observed that channels (300 microm) created in
      scaffolds were effective at enhancing cellular infiltration and vascularization.
      Our results have demonstrated that CP is a viable method for fabricating
      scaffolds for a wide range of tissue engineering applications.

PMID- 20694999
TI  - Fiber diameters control osteoblastic cell migration and differentiation in
      electrospun gelatin.
AB  - Defined electrospinning conditions were used to create scaffolds with different
      fiber diameters to investigate their interactions with osteoblastic MG63 cells.
      Nonwoven gelatin scaffolds were electrospun with varied fiber diameters to
      investigate the effect of fiber size and resultant porosity on cell
      proliferation, viability, migration, and differentiation. The low toxicity
      solvent acetic acid:ethyl acetate:water ratio and gelatin concentrations were
      optimized to create small and large diameter fibers. The fiber diameters obtained
      by this procedure were 110 +/- 40 nm for the small and 600 +/- 110 nm for the
      large fibers. Cell viability assays showed that MG63 cells grew similarly on both
      fibers at the early time point (day 3) but preferred the scaffold with large
      diameter fibers by the later time points (day 5 and day 7). Confocal microscopic
      imaging showed that MG63 cells migrated poorly (maximum depth of 18 microm) into
      the scaffold of small diameter fibers, but readily penetrated (maximum depth of
      50 microm) into the scaffold of large diameter fibers. Alkaline phosphatase (ALP)
      assays showed that MG63 cells differentiated on scaffolds made from both diameter
      fibers. In longer term experiments, MG63 cells differentiated to a greater extent
      on scaffolds made from small diameter fibers compared to large diameter fibers at
      days 3 and 7, but the ALP levels were the same for both diameter fibers by day
      14. These results indicate that cells can perceive differences in the diameter
      and resultant pore size of electrospun gelatin fibers and that they process this
      information to alter their behavior.

PMID- 20695003
TI  - The challenge of publishing newsworthy epidemiology.

PMID- 20695004
TI  - Interruption of SOX10 function in myelinopathies.

PMID- 20695005
TI  - A review of paroxysmal sympathetic hyperactivity after acquired brain injury.
AB  - Severe excessive autonomic overactivity occurs in a subgroup of people surviving
      acquired brain injury, the majority of whom show paroxysmal sympathetic and motor
      overactivity. Delayed recognition of paroxysmal sympathetic hyperactivity (PSH)
      after brain injury may increase morbidity and long-term disability. Despite its
      significant clinical impact, the scientific literature on this syndrome is
      confusing; there is no consensus on nomenclature, etiological information for
      diagnoses preceding the condition is poorly understood, and the evidence base
      underpinning our knowledge of the pathophysiology and management strategies is
      largely anecdotal. This systematic literature review identified 2 separate
      categories of paroxysmal autonomic overactivity, 1 characterized by relatively
      pure sympathetic overactivity and another group of disorders with mixed
      parasympathetic/sympathetic features. The PSH group comprised 349 reported cases,
      with 79.4% resulting from traumatic brain injury (TBI), 9.7% from hypoxia, and
      5.4% from cerebrovascular accident. Although TBI is the dominant causative
      etiology, there was some suggestion that the true incidence of the condition is
      highest following cerebral hypoxia. In total, 31 different terms were identified
      for the condition. Although the most common term in the literature was
      dysautonomia, the consistency of sympathetic clinical features suggests that a
      more specific term should be used. The findings of this review suggest that PSH
      be adopted as a more clinically relevant and appropriate term. The review
      highlights major problems regarding conceptual definitions, diagnostic criteria,
      and nomenclature. Consensus on these issues is recommended as an essential basis
      for further research in the area.

PMID- 20695007
TI  - Pilot trial of low-dose naltrexone and quality of life in multiple sclerosis.
AB  - OBJECTIVE: To evaluate the efficacy of 4.5mg nightly naltrexone on the quality of
      life of multiple sclerosis (MS) patients. METHODS: This single-center, double
      masked, placebo-controlled, crossover study evaluated the efficacy of 8 weeks of
      treatment with 4.5mg nightly naltrexone (low-dose naltrexone, LDN) on self
      reported quality of life of MS patients. RESULTS: Eighty subjects with clinically
      definite MS were enrolled, and 60 subjects completed the trial. Ten withdrew
      before completing the first trial period: 8 for personal reasons, 1 for a non-MS
      related adverse event, and 1 for perceived benefit. Database management errors
      occurred in 4 other subjects, and quality of life surveys were incomplete in 6
      subjects for unknown reasons. The high rate of subject dropout and data
      management errors substantially reduced the trial's statistical power. LDN was
      well tolerated, and serious adverse events did not occur. LDN was associated with
      significant improvement on the following mental health quality of life measures:
      a 3.3-point improvement on the Mental Component Summary score of the Short Form
      36 General Health Survey (p = 0.04), a 6-point improvement on the Mental Health
      Inventory (p < 0.01), a 1.6-point improvement on the Pain Effects Scale (p =.04),
      and a 2.4-point improvement on the Perceived Deficits Questionnaire (p = 0.05).
      INTERPRETATION: LDN significantly improved mental health quality of life indices.
      Further studies with LDN in MS are warranted.

PMID- 20695006
TI  - Visceral fat is associated with lower brain volume in healthy middle-aged adults.
AB  - OBJECTIVE: Midlife obesity has been associated with an increased risk of
      dementia. The underlying mechanisms are poorly understood. Our aim was to examine
      the cross-sectional association of body mass index (BMI), waist circumference
      (WC), waist-to-hip ratio (WHR), and computed tomography (CT)-based measurements
      of subcutaneous (SAT) and visceral (VAT) adipose tissue with various magnetic
      resonance imaging (MRI) markers of brain aging in middle-aged community adults.
      METHODS: Participants from the Framingham Offspring cohort were eligible if in
      addition to having measurements of BMI, WC, WHR, SAT, and VAT, they had undergone
      a volumetric brain MRI scan with measurements of total brain volume (TCBV),
      temporal horn volume (THV), white matter hyperintensity volume (WMHV), and MRI
      defined brain infarcts (BI). All analyses were adjusted for age, sex, and time
      interval between abdominal CT and brain MRI. RESULTS: In a sample of 733
      community participants (mean age, 60 years; 53% women), we observed an inverse
      association of BMI (estimate by standard deviation unit +/- standard error = 
      0.27 +/- 0.12; p = 0.02), WC (-0.30 +/- 0.12; p = 0.01), WHR (-0.37 +/- 0.12; p =
      0.02), SAT (-0.23 +/- 0.11; p = 0.04), and VAT (-0.36 +/- 0.12; p = 0.002) with
      TCBV, independent of vascular risk factors. The association between VAT and TCBV
      was the strongest and most robust, and was also independent of BMI (-0.35 +/-
      0.15; p = 0.02) and insulin resistance (-0.32 +/- 0.13; p = 0.01). When adjusting
      for C-reactive protein levels, the associations were attenuated (-0.17 +/- 0.13;
      p = 0.17 for VAT). No consistently significant association was observed between
      the anthropometric or CT-based abdominal fat measurements and THV, WMHV, or BI.
      INTERPRETATION: In middle-aged community participants, we observed a significant
      inverse association of anthropometric and CT-based measurements of abdominal,
      especially visceral, fat with total brain volume.

PMID- 20695008
TI  - Human prion strain selection in transgenic mice.
AB  - OBJECTIVE: Transgenic (Tg) mice expressing chimeras of mouse and human prion
      proteins (PrPs) have shorter incubation periods for Creutzfeldt-Jakob disease
      (CJD) prions than mice expressing full-length human PrP. Increasing the sequence
      similarity of the chimeric PrP to mouse PrP, by reverting human residues to
      mouse, resulted in a Tg line, denoted Tg22372, which was susceptible to sporadic
      (s) CJD prions in approximately 110 days. METHODS: Mice expressing chimeric
      mouse/human PrP transgenes were produced. The mice were inoculated
      intracerebrally with extracts prepared from the brains of patients who died of
      CJD. Onset of neurological dysfunction marked the end of the incubation time.
      After sacrifice of the Tg mice, their brains were analyzed for PrP(Sc) and
      neuropathological changes. RESULTS: Reversion of 1 additional residue (M111V)
      resulted in a new Tg line, termed Tg1014, susceptible to sCJD prions in
      approximately 75 days. Tg1014 mice also have shorter incubation periods for
      variant (v) CJD prions, providing a more tractable model for studying this prion
      strain. Transmission of vCJD prions to Tg1014 mice resulted in 2 different
      strains, determined by neuropathology and biochemical analysis, which correlated
      with the length of the incubation time. One strain had the biochemical,
      neuropathological, and transmission characteristics, including longer incubation
      times, of the inoculated vCJD strain; the second strain produced a phenotype
      resembling that of sCJD prions including relatively shorter incubation periods.
      Mice with intermediate incubation periods for vCJD prions had a mixture of the 2
      strains. Both strains were serially transmitted in Tg1014 mice, which led to
      further reduction in incubation periods. Conversion of vCJD-like to sCJD-like
      strains was favored in Tg1014 mice more than in the Tg22372 line. The single
      amino acid difference therefore appears to offer selective pressure for
      propagation of the sCJD-like strain. INTERPRETATION: These 2 Tg mouse lines
      provide relatively rapid models to study human prion diseases as well as the
      evolution of human prion strains.

PMID- 20695010
TI  - No cerebrocervical venous congestion in patients with multiple sclerosis.
AB  - OBJECTIVE: Multiple sclerosis (MS) is characterized by demyelination centered
      around cerebral veins. Recent studies suggested this topographic pattern may be
      caused by venous congestion, a condition termed chronic cerebrospinal venous
      insufficiency (CCSVI). Published sonographic criteria of CCSVI include reflux in
      the deep cerebral veins and/or the internal jugular and vertebral veins (IJVs and
      VVs), stenosis of the IJVs, missing flow in IJVs and VVs, and inverse postural
      response of the cerebral venous drainage. METHODS: We performed an extended extra
      and transcranial color-coded sonography study including analysis of extracranial
      venous blood volume flow (BVF), cross-sectional areas, IJV flow analysis during
      Valsalva maneuver (VM), and CCSVI criteria. Fifty-six MS patients and 20 controls
      were studied. RESULTS: Except for 1 patient, blood flow direction in the IJVs and
      VVs was normal in all subjects. In none of the subjects was IJV stenosis
      detected. IJV and VV BVF in both groups was equal in the supine body position.
      The decrease of total jugular BVF on turning into the upright position was less
      pronounced in patients (173 +/- 235 vs 362 +/- 150 ml/min, p < 0.001), leading to
      higher BVF in the latter position (318 ml/min +/- 242 vs 123 +/- 109 ml/min; p <
      0.001). No differences between groups were seen in intracranial veins and during
      VM. None of the subjects investigated in this study fulfilled >1 criterion for
      CCSVI. INTERPRETATION: Our results challenge the hypothesis that cerebral venous
      congestion plays a significant role in the pathogenesis of MS. Future studies
      should elucidate the difference between patients and healthy subjects in BVF
      regulation.

PMID- 20695009
TI  - Variably protease-sensitive prionopathy: a new sporadic disease of the prion
      protein.
AB  - OBJECTIVE: The objective of the study is to report 2 new genotypic forms of
      protease-sensitive prionopathy (PSPr), a novel prion disease described in 2008,
      in 11 subjects all homozygous for valine at codon 129 of the prion protein (PrP)
      gene (129VV). The 2 new PSPr forms affect individuals who are either homozygous
      for methionine (129MM) or heterozygous for methionine/valine (129MV). METHODS:
      Fifteen affected subjects with 129MM, 129MV, and 129VV underwent comparative
      evaluation at the National Prion Disease Pathology Surveillance Center for
      clinical, histopathologic, immunohistochemical, genotypical, and PrP
      characteristics. RESULTS: Disease duration (between 22 and 45 months) was
      significantly different in the 129VV and 129MV subjects. Most other phenotypic
      features along with the PrP electrophoretic profile were similar but
      distinguishable in the 3 129 genotypes. A major difference laid in the
      sensitivity to protease digestion of the disease-associated PrP, which was high
      in 129VV but much lower, or altogether lacking, in 129MV and 129MM. This
      difference prompted the substitution of the original designation with "variably
      protease-sensitive prionopathy" (VPSPr). None of the subjects had mutations in
      the PrP gene coding region. INTERPRETATION: Because all 3 129 genotypes are
      involved, and are associated with distinguishable phenotypes, VPSPr becomes the
      second sporadic prion protein disease with this feature after Creutzfeldt-Jakob
      disease, originally reported in 1920. However, the characteristics of the
      abnormal prion protein suggest that VPSPr is different from typical prion
      diseases, and perhaps more akin to subtypes of Gerstmann-Straussler-Scheinker
      disease.

PMID- 20695011
TI  - Apoptosis-inducing factor deficiency sensitizes dopaminergic neurons to
      parkinsonian neurotoxins.
AB  - OBJECTIVE: Mitochondrial complex I deficits have long been associated with
      Parkinson disease (PD). However, it remains unknown whether such defects
      represent a primary event in dopaminergic neurodegeneration. METHODS: Apoptosis
      inducing factor (AIF) is a mitochondrial protein that, independently of its
      proapoptotic properties, plays an essential physiologic role in maintaining a
      fully functional complex I. We used AIF-deficient harlequin (Hq) mice, which
      exhibit structural deficits in assembled complex I, to determine whether primary
      complex I defects linked to AIF depletion may cause dopaminergic
      neurodegeneration. RESULTS: Despite marked reductions in mitochondrial complex I
      protein levels, Hq mice did not display apparent alterations in the dopaminergic
      nigrostriatal system. However, these animals were much more susceptible to
      exogenous parkinsonian complex I inhibitors, such as 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP). Subtoxic doses of MPTP, unable to cause damage to wild
      type animals, produced marked nigrostriatal dopaminergic degeneration in Hq mice.
      This effect was associated with exacerbated complex I inhibition and increased
      production of mitochondrial-derived reactive oxygen species (ROS) in Hq brain
      mitochondria. The antioxidant superoxide dismutase-mimetic compound tempol was
      able to reverse the increased susceptibility of Hq mice to MPTP. Supporting an
      instrumental role for mitochondrial-derived ROS in PD-related neurodegeneration,
      transgenic mice overexpressing mitochondrially targeted catalase exhibited an
      attenuation of MPTP-induced mitochondrial ROS and dopaminergic cell death.
      INTERPRETATION: Structural complex I alterations linked to AIF deficiency do not
      cause dopaminergic neurodegeneration but increase the susceptibility of
      dopaminergic neurons to exogenous parkinsonian neurotoxins, reinforcing the
      concept that genetic and environmental factors may interact in a common molecular
      pathway to trigger PD.

PMID- 20695012
TI  - Higher 25-hydroxyvitamin D is associated with lower relapse risk in multiple
      sclerosis.
AB  - OBJECTIVE: A protective association between higher vitamin D levels and the onset
      of multiple sclerosis (MS) has been demonstrated; however, its role in modulating
      MS clinical course has been little studied. We investigated whether higher levels
      of serum 25-hydroxyvitamin D (25-OH-D) were associated with a lower risk of
      relapses in people with MS. METHODS: We conducted a prospective cohort study of
      145 participants with relapsing-remitting MS from 2002 to 2005. Serum 25-OH-D
      levels were measured biannually, and the hazard of relapse was assessed using
      survival analysis. RESULTS: There was an inverse linear relationship between 25
      OH-D levels and the hazard of relapse over the subsequent 6 months, with hazard
      ratio (HR) 0.91 (95% confidence interval [CI]: 0.85-0.97) per 10 nmol/l increase
      in 25-OH-D level (p = 0.006). When variation due to timing of blood collection
      was removed by estimating 25-OH-D at the start of each season, this association
      persisted, with HR 0.90 (95% CI, 0.83-0.98) per 10 nmol/l increase (p = 0.016).
      Taking into account the biological half-life of 25-OH-D, we estimated 25-OH-D at
      monthly intervals, resulting in a slightly enhanced association, with HR 0.88
      (95% CI, 0.82-0.95) per 10 nmol/l increase (p = 0.001). Adjusting for potential
      confounders did not alter these findings. INTERPRETATION: In this prospective
      population-based cohort study, in a cohort largely on immunomodulatory therapy,
      higher 25-OH-D levels were associated with a reduced hazard of relapse. This
      occurred in a dose-dependent linear fashion, with each 10 nmol/l increase in 25
      OH-D resulting in up to a 12% reduction in risk of relapse. Clinically, raising
      25-OH-D levels by 50 nmol/l could halve the hazard of a relapse.

PMID- 20695013
TI  - Altered inflammatory responses in preterm children with cerebral palsy.
AB  - OBJECTIVE: Perinatal inflammatory responses contribute to periventricular
      leukomalacia (PVL) and cerebral palsy (CP) in preterm infants. Here, we examined
      whether preterm children with CP had altered inflammatory responses when school
      aged. METHODS: Thirty-two preterm children with PVL-induced CP (mean [+/-standard
      deviation] age, 7.2 +/- 3.6 years) and 32 control preterm children with normal
      neurodevelopment (6.2 +/- 2.2 years) and matched for gestational age were
      recruited. We measured tumor necrosis factor (TNF)-alpha levels in the plasma and
      the supernatants of peripheral blood mononuclear cells (PBMCs) before and after
      lipopolysaccharide (LPS) stimulation, and proinflammatory gene expression in the
      PBMCs. RESULTS: TNF-alpha expression was significantly higher in the plasma (p <
      0.001) and supernatants of LPS-stimulated PBMCs (p = 0.003) in the CP group than
      in the control group. After LPS stimulation, the intracellular TNF-alpha level in
      the PBMCs was significantly lower in the control group (p = 0.016) and
      significantly higher in the CP group (p = 0.01). The CP group also had, in their
      nonstimulated PBMCs, significantly higher mRNA levels of inflammatory molecules:
      toll-like receptor 4 (TLR-4) (p = 0.0023), TNF-alpha (p = 0.0016), transforming
      growth factor-beta-activated kinase 1 (p = 0.038), IkappaB kinase-gamma (p =
      0.029), and c-Jun N-terminal kinase (p = 0.045). The TLR-4 mRNA levels in the
      PBMCs were highly correlated with TNF-alpha levels in LPS-stimulated PBMCs
      (Spearman rank correlation = 0.38, p = 0.03). INTERPRETATION: The finding that
      preterm children with PVL-induced CP have altered inflammatory responses
      indicates the possibility of programming effect of PVL or inflammation-related
      events during early life.

PMID- 20695014
TI  - Coagulopathy and embolic signal in cancer patients with ischemic stroke.
AB  - OBJECTIVE: It has been reported that embolic signal (ES) detected by transcranial
      Doppler (TCD) has clinical significance, especially in patients with recent
      stroke attributable to arterial or cardiac embolism. Therefore, we conducted this
      study to determine whether the prevalence of ES is high in ischemic stroke
      patients with cancer and related to hypercoagulopathy. METHODS: We prospectively
      studied cancer patients with acute ischemic stroke within the middle cerebral
      artery (MCA) distribution on diffusion-weighted imaging. Conventional stroke
      mechanisms (CSMs) were determined using cardiologic and vascular studies.
      Additionally, the coagulation status was assessed based on the serum D-dimer
      levels, and TCD monitoring was performed on both MCAs for 30 minutes to detect
      ES. Clinical features including vascular risk factors, characteristics of
      ischemic stroke, and cancer and laboratory findings associated with the presence
      of ES were evaluated. RESULTS: A total of 74 patients were finally included in
      this study. ES was more commonly observed in patients without CSMs (22 of 38
      patients, 57.9%) than in those with CSMs (12 of 36 patients, 33.3%) (p = 0.034).
      Moreover, ES was more commonly detected in patients with high D-dimer levels (p <
      0.001), and D-dimer levels were significantly correlated with the number of ESs
      in patients without CSMs (r = 0.732, p < 0.001), but were poorly correlated in
      patients with CSMs (r = 0.152, p = 0.375). Higher levels of D-dimer (odds ratio
      [OR], 1.082 per 1 microg/ml increase; 95% confidence interval [CI], 1.014-1.154)
      and adenocarcinoma (OR, 3.829; 95% CI, 1.23-13.052) were independently associated
      with the presence of ES. The use of anticoagulants dramatically decreased the D
      dimer levels. INTERPRETATION: A high prevalence of ES was observed in cancer
      patients with ischemic stroke, especially in those without CSMs. Elevated D-dimer
      levels were independently associated with ES, and decreased dramatically with the
      use of anticoagulants. ANN NEUROL 2010;68:213-219.

PMID- 20695015
TI  - Atherosclerosis, dementia, and Alzheimer disease in the Baltimore Longitudinal
      Study of Aging cohort.
AB  - OBJECTIVE: Although it is now accepted that asymptomatic cerebral infarcts are an
      important cause of dementia in the elderly, the relationship between
      atherosclerosis per se and dementia is controversial. Specifically, it is unclear
      whether atherosclerosis can cause the neuritic plaques and neurofibrillary
      tangles that define Alzheimer neuropathology and whether atherosclerosis, a
      potentially reversible risk factor, can influence cognition independent of brain
      infarcts. METHODS: We examined the relationship between systemic atherosclerosis,
      Alzheimer type pathology, and dementia in autopsies from 200 participants in the
      Baltimore Longitudinal Study of Aging, a prospective study of the effect of aging
      on cognition, 175 of whom had complete body autopsies. RESULTS: Using a
      quantitative analysis of atherosclerosis in the aorta, heart, and intracranial
      vessels, we found no relationship between the degree of atherosclerosis in any of
      these systems and the degree of Alzheimer type brain pathology. However, we found
      that the presence of intracranial but not coronary or aortic atherosclerosis
      significantly increased the odds of dementia, independent of cerebral infarction.
      Given the large number of individuals with intracranial atherosclerosis in this
      cohort (136/200), the population attributable risk of dementia related to
      intracranial atherosclerosis (independent of infarction) is substantial and
      potentially reversible. INTERPRETATION: Atherosclerosis of the intracranial
      arteries is an independent and important risk factor for dementia, suggesting
      potentially reversible pathways unrelated to Alzheimer pathology and stroke
      through which vascular changes may influence dementia risk.

PMID- 20695016
TI  - Voxel-based morphometry depicts central compensation after vestibular neuritis.
AB  - OBJECTIVE: Patients who have had vestibular neuritis (VN) show a remarkable
      clinical improvement especially in gait and posture >6 months after disease
      onset. METHODS: Voxel-based morphometry was used to detect the VN-induced changes
      in gray and white matter by means of structural magnetic resonance imaging.
      Twenty-two patients were compared an average 2.5 years after onset of VN to a
      healthy sex-and age-matched control group. RESULTS: Our analysis revealed that
      all patients had signal intensity increases for gray matter in the medial
      vestibular nuclei and the right gracile nucleus and for white matter in the area
      of the pontine commissural vestibular fibers. A relative atrophy was observed in
      the left posterior hippocampus and the right superior temporal gyrus. Patients
      with a residual canal paresis also showed an increase of gray matter in middle
      temporal (MT)/V5 bilaterally. INTERPRETATION: These findings indicate that the
      processes of central compensation after VN seem to occur in 3 different sensory
      systems. First of all, the vestibular system itself showed a white matter
      increase in the commissural fibers as a direct consequence of an increased
      internuclei vestibular crosstalk of the medial vestibular nuclei. Second, to
      regain postural stability, there was a shift to the somatosensory system due to
      an elevated processing of proprioceptive information in the right gracile
      nucleus. Third, there was a bilateral increase in the area of MT/V5 in VN
      patients with a residual peripheral vestibular hypofunction. This seems to be the
      result of an increased importance of visual motion processing.

PMID- 20695017
TI  - Disrupted SOX10 regulation of GJC2 transcription causes Pelizaeus-Merzbacher-like
      disease.
AB  - Mutations in the gap junction protein gamma-2 gene, GJC2, cause a central
      hypomyelinating disorder; Pelizaeus-Merzbacher-like disease (PMLD; MIM311601).
      Using a homozygosity mapping and positional candidate gene approach, we
      identified a homozygous mutation (c.-167A>G) within the GJC2 promoter at a potent
      SOX10 binding site in a patient with mild PMLD. Functionally, this mutation
      completely abolished the SOX10 binding and attenuated GJC2 promoter activity.
      These findings suggest not only that the SOX10-to-GJC2 transcriptional
      dysregulation is a cause of PMLD, but also that GJC2 may be in part responsible
      for the central hypomyelination caused by SOX10 mutations.

PMID- 20695018
TI  - Venous and cerebrospinal fluid flow in multiple sclerosis: a case-control study.
AB  - The prevailing view on multiple sclerosis etiopathogenesis has been challenged by
      the suggested new entity chronic cerebrospinal venous insufficiency. To test this
      hypothesis, we studied 21 relapsing-remitting multiple sclerosis cases and 20
      healthy controls with phase-contrast magnetic resonance imaging. In addition, in
      multiple sclerosis cases we performed contrast-enhanced magnetic resonance
      angiography. We found no differences regarding internal jugular venous outflow,
      aqueductal cerebrospinal fluid flow, or the presence of internal jugular blood
      reflux. Three of 21 cases had internal jugular vein stenoses. In conclusion, we
      found no evidence confirming the suggested vascular multiple sclerosis
      hypothesis.

PMID- 20695019
TI  - Mutations in PEX10 are a cause of autosomal recessive ataxia.
AB  - Peroxisomal biogenesis disorders typically cause severe multisystem disease and
      early death. We describe a child and an adult of normal intelligence with
      progressive ataxia, axonal motor neuropathy, and decreased vibration sense. Both
      patients had marked cerebellar atrophy. Peroxisomal studies revealed a
      peroxisomal biogenesis disorder. Two mutations in PEX10 were found in the child,
      c.992G>A (novel) and c.764_765insA, and in the adult, c.2T>C (novel) and
      c.790C>T. Transfection with wild-type PEX10 corrected the fibroblast phenotype.
      Bile acid supplements and dietary restriction of phytanic acid were started.
      Peroxisomal biogenesis disorders should be considered in the differential
      diagnosis of autosomal recessive ataxia.

PMID- 20695021
TI  - Chronic cerebrospinal venous insufficiency and multiple sclerosis.

PMID- 20695020
TI  - Residual tumor cells are unique cellular targets in glioblastoma.
AB  - Residual tumor cells remain beyond the margins of every glioblastoma (GBM)
      resection. Their resistance to postsurgical therapy is considered a major driving
      force of mortality, but their biology remains largely uncharacterized. In this
      study, residual tumor cells were derived via experimental biopsy of the resection
      margin after standard neurosurgery for direct comparison with samples from the
      routinely resected tumor tissue. In vitro analysis of proliferation, invasion,
      stem cell qualities, GBM-typical antigens, genotypes, and in vitro drug and
      irradiation challenge studies revealed these cells as unique entities. Our
      findings suggest a need for characterization of residual tumor cells to optimize
      diagnosis and treatment of GBM.

PMID- 20695022
TI  - Quasi-amorphous inorganic thin films: non-crystalline polar phases.
AB  - Quasi-amorphous thin films of BaTiO3, SrTiO3, and BaZrO3 are the only known
      examples of inorganic, non-crystalline, polar materials. The conditions under
      which they are formed and the origin of their polarity set these materials apart
      from other classes of inorganic materials. The most important feature of the
      quasi-amorphous phase is that the polarity is the result of the orientational
      ordering of local bonding units but without any detectable spatial periodicity.
      This mechanism is reminiscent of that observed in ferroelectric polymers and
      permits compounds that do not have polar crystalline polymorphs, such as SrTiO3
      and BaZrO3, to form polar non-crystalline solids. In the present report, we
      provide an overview of the essential features of these materials including
      preparation, structure, and chemical composition. The report also reviews our
      current level of understanding and offers some guidelines for further development
      and application of non-crystalline inorganic polar materials.

PMID- 20695023
TI  - Direct patterning of oriented metal-organic framework crystals via control over
      crystallization kinetics in clear precursor solutions.

PMID- 20695024
TI  - Biology of fungal cell walls--from single proteins to regulatory networks.

PMID- 20695025
TI  - Application of AFM in microbiology: a review.
AB  - Atomic force microscopy (AFM) is a powerful tool for microbiological
      investigation. This versatile technique cannot only image cellular surfaces at
      high resolution, but also measure many forms of fundamental interactions over
      scales ranging from molecules to cells. In this work, we review the recent
      development of AFM applications in the microbial area. We discuss several
      approaches for using AFM scanning images to investigate morphological
      characteristics of microbes and the use of force-distance curves to investigate
      interaction of microbial samples at the nanometer and cellular levels.
      Complementary techniques used in combination with AFM for study of microbes are
      also discussed.

PMID- 20695026
TI  - Application of atomic force microscopy in bacterial research.
AB  - The atomic force microscope (AFM) has evolved from an imaging device into a
      multifunctional and powerful toolkit for probing the nanostructures and surface
      components on the exterior of bacterial cells. Currently, the area of application
      spans a broad range of interesting fields from materials sciences, in which AFM
      has been used to deposit patterns of thiol-functionalized molecules onto gold
      substrates, to biological sciences, in which AFM has been employed to study the
      undesirable bacterial adhesion to implants and catheters or the essential
      bacterial adhesion to contaminated soil or aquifers. The unique attribute of AFM
      is the ability to image bacterial surface features, to measure interaction forces
      of functionalized probes with these features, and to manipulate these features,
      for example, by measuring elongation forces under physiological conditions and at
      high lateral resolution (<1 A). The first imaging studies showed the morphology
      of various biomolecules followed by rapid progress in visualizing whole bacterial
      cells. The AFM technique gradually developed into a lab-on-a-tip allowing more
      quantitative analysis of bacterial samples in aqueous liquids and non-contact
      modes. Recently, force spectroscopy modes, such as chemical force microscopy,
      single-cell force spectroscopy, and single-molecule force spectroscopy, have been
      used to map the spatial arrangement of chemical groups and electrical charges on
      bacterial surfaces, to measure cell-cell interactions, and to stretch
      biomolecules. In this review, we present the fascinating options offered by the
      rapid advances in AFM with emphasizes on bacterial research and provide a
      background for the exciting research articles to follow.

PMID- 20695027
TI  - A systematic method for predetermined scanning electron microscope analysis in
      dental science.
AB  - Scanning electron microscope evaluation could be criticized if the method adopted
      to correct for bias is not specified in the study design. Observers can draw
      conclusions from images unconsciously chosen to best support their research
      hypotheses, impairing the basic research principle of operator's impartiality. In
      this study, a systematic observation method has been described and verified for
      repeatability. The number and the observation points on a certain specimen have
      been predetermined using a scheme along with observation rules previously
      established in the research protocol. When our instrument is used at an operating
      magnification between 500x and 1,000x (corresponding to a frame of 250x190 micro
      and 120x90 micro, respectively), the method allowed 100% repeatable observation
      frames, with linear frame errors in finding an observation point of 12.5% in
      length and 16.8% in height. With modifications to accommodate research objective
      and statistical requirements, the method could be applied to many SEM observation
      study.

PMID- 20695028
TI  - Evaluation of residents' competency in professionalism and communication skills
      in northern China: a 360-degree assessment.

PMID- 20695029
TI  - Evaluating effectiveness and usability of an e-learning portal: the e-MedEdu
      site.

PMID- 20695030
TI  - Research using SSCs.

PMID- 20695031
TI  - Using videotaped vignettes to improve the teaching quality in child and
      adolescent psychiatry.

PMID- 20695032
TI  - Posttraumatic stress disorder in cancer ICUs.

PMID- 20695033
TI  - Non-invasive magnetic resonance imaging of blood vessel growth in tumors using
      nanosized contrast agents.

PMID- 20695034
TI  - Cannabidiol inhibitory effect on marble-burying behaviour: involvement of CB1
      receptors.
AB  - Cannabidiol (CBD) is a major non-psychotomimetic component of Cannabis sativa
      that has been shown to have an anxiolytic effect in human and animal models.
      Earlier studies suggest that these effects involve facilitation of serotonin, a
      neurotransmitter that has also been related to obsessive-compulsive disorder. On
      the basis of this evidence, this study investigated the effects of CBD in
      C57BL/6J mice submitted to the marble-burying test (MBT), an animal model
      proposed to reflect compulsive behaviour. CBD (15, 30 and 60 mg/kg) induced a
      significant decrease in the number of buried marbles compared with controls (34,
      41 and 48%, respectively). A similar, although larger, decrease was also found
      after the serotonin selective reuptake inhibitor paroxetine (10 mg/kg, 77%
      decrease) and the benzodiazepine diazepam (2.5 mg/kg, 84% decrease). The effect
      of CBD (30 mg/kg) was still significant after 7 days of daily repeated
      administration, whereas the effect of diazepam disappeared. Pretreatment with
      WAY100635 (3 mg/kg), a 5HT1A receptor antagonist, prevented the effects of
      paroxetine but failed to alter those of CBD. These latter effects, however, were
      prevented by pretreatment with the CB1 receptor antagonist AM251 (1 mg/kg). These
      results indicated that CBD and paroxetine decrease the number of buried marbles
      in the MBT through distinct pharmacological mechanisms. They also suggest a
      potential role of drugs acting on the cannabinoid system in modulating compulsive
      behaviour.

PMID- 20695035
TI  - Spousal agreement on maternal health practices in Kathmandu, Nepal.
AB  - Growing recognition of the influential roles that men play in health behaviours
      and decision-making has prompted a number of couples' agreement studies,
      particularly in the areas of contraceptive use and household decision-making.
      While such findings have had important implications on the design, measurement
      and evaluation of family planning interventions, few studies on couples'
      agreement on maternal health behaviours have been conducted. Findings from a
      descriptive analysis of agreement levels regarding maternal health practices
      among 129 couples that delivered a baby in urban Nepal in 2003-2004 are
      presented. These data indicate that agreement levels between husbands and wives
      pertaining to maternal health behaviours are low, with 5-55% of couples
      disagreeing on whether the behaviour had occurred. These data and the surrounding
      discussion raise important issues that ought to be taken into consideration when
      conducting maternal health research and designing and evaluating maternal health
      programmes.

PMID- 20695036
TI  - Measuring the usefulness of family planning job aids following distribution at
      training workshops.
AB  - A job aid is a tool, such as a flowchart or checklist, that makes it easier for
      staff to carry out tasks by providing quick access to needed information. Many
      public health organizations are engaged in the production of job aids intended to
      improve adherence to important medical guidelines and protocols, particularly in
      resource-constrained countries. However, some evidence suggests that actual use
      of job aids remains low. One strategy for improving utilization is the
      introduction of job aids in training workshops. This paper summarizes the results
      of two separate evaluations conducted in Uganda and the Dominican Republic (DR)
      which measured the usefulness of a series of four family planning checklists 7-24
      months after distribution in training workshops. While more than half of the
      health care providers used the checklists at least once, utilization rates were
      sub-optimal. However, the vast majority of those providers who utilized the
      checklists found them to be very useful in their work.

PMID- 20695037
TI  - TRICARE; diabetic education. Final rule.
AB  - The Department of Defense is publishing this final rule to clarify TRICARE
      coverage for diabetic education. This rule introduces new definitions and
      addresses revisions or omissions in policy or procedure inadvertently missed in
      previous regulatory changes pertaining to diabetic education.

PMID- 20695038
TI  - Findings of research misconduct.

PMID- 20695039
TI  - Preventing primary postpartum hemorrhage in unskilled births in Africa.

PMID- 20695040
TI  - Knowledge of HIV and AIDS in women in sub-Saharan Africa.
AB  - Although most African people have heard of HIV and AIDS, there is still
      widespread misunderstanding about how HIV is spread, the consequences of
      infection, and how to protect against infection. The most vulnerable groups are
      poorly educated women, those from rural backgrounds, and women who are
      economically dependent on men. Lower levels of education, taboos associated with
      the discussion of sexuality and sexual health, the submissive role of women in a
      relationship, and male control of decision-making regarding sexual relations
      might explain why African women are less knowledgeable about HIV/AIDS than men.
      Although most African men and women are aware of the protective benefits of
      condoms, negative attitudes towards the acceptability and safety of condom use
      are widespread. More sexual health campaigns tailored to women, especially those
      with low education levels and those from rural areas, are needed to reduce the
      spread of HIV in Africa.

PMID- 20695041
TI  - Family planning methods among women in a vaginal microbicide feasibility study in
      rural KwaZulu-Natal, South Africa.
AB  - This study investigated contraceptive use among women in rural KwaZulu-Natal,
      South Africa. Of 866 sexually active women not intending pregnancy and screened
      for a microbicide feasibility study, 466 (54%) reported currently using modern
      contraceptives: injectables (31%), condoms (12%), sterilization (60%) and pills
      (4%). Multivariable logistic regression analyses revealed statistically
      significantly higher odds of current contraceptive use among married vs.
      engaged/unmarried women (aOR 1.64), multiparous vs. nulliparous (aOR 4.45) and
      women who completed secondary education or above vs. primary or less (aOR 1.64).
      Significantly lower odds of use were observed among women aged 40+ vs. age 15-19
      (aOR 0.38). Age, marital status, education level and parity were associated with
      different contraceptive method choices. Among 195 women followed longitudinally
      for 9 months, contraceptive use increased significantly from 56% to 70%, largely
      due to increased condom use (15% to 28%). Results highlight the importance of
      integrating family planning and HIV/STI prevention counseling and informing
      promotion of further contraceptive uptake among women not intending pregnancy.

PMID- 20695042
TI  - Premarital fertility and HIV/AIDS in sub-Saharan Africa.
AB  - The paper investigates the complex relationships between premarital fertility and
      HIV/AIDS in sub-Saharan African countries. The DHS surveys provided data to
      compute the prevalence of premarital fertility, defined as any birth before the
      first marriage. The UNAIDS database provided data to compute the prevalence of
      HIV infection among pregnant women. Results indicate a moderate association
      between the prevalence of premarital fertility and the prevalence of HIV
      infection (correlation coefficient = 0.64, P < 0.0001), and similar geographical
      patterns. Compared with the average pattern, outlier countries had either high
      levels of premarital fertility and relatively low HIV prevalence (Liberia,
      Madagascar, Gabon, Congo), or high levels of HIV prevalence despite low levels of
      premarital fertility (Lesotho, Malawi, Zambia, Zimbabwe). The overall
      relationship is discussed in light of the relationships between age at marriage,
      permissiveness and lack of protection during intercourse and their impact on
      premarital fertility and HIV infection among women.

PMID- 20695043
TI  - Child sexual abuse, harmful alcohol use and age as determinants of sexual risk
      behaviours among freshmen in a Nigerian university.
AB  - In Nigeria, freshmen constitute a risk group of adolescents and young adults
      capable of engaging in unsafe sexual practices. This study documents the
      associated factors to sexual risk behaviours practices of University of Ibadan,
      Nigeria freshmen. Eight hundred and forty one (841), freshmen who attended a
      routine orientation program were asked to respond to a questionnaire. Results
      showed that 30.8% were sexually active and 47% did not use condom in their last
      sexual episode. Associated with sexual risk behaviours include: being a male
      freshman increasing age; lower tendency for violence; increase sexual
      compulsivity; alcohol abuse; history of rape and a history of Child Sexual Abuse
      (CSA). Three variables: alcohol abuse; history of CSA and increasing age remained
      significant in a multiple regression analysis. The paper presents the first
      evidence of vulnerability of freshmen to sexual risk practices in a Nigerian
      University.

PMID- 20695044
TI  - Sexual behaviour of in-school adolescents in Ibadan, South-West Nigeria.
AB  - This study was a crossectional survey conducted among 716 senior secondary school
      adolescents in Ibadan from March to August 2005. The result of 695 that was
      analyzed revealed that the mean age of 15 +/- 2.6years. 28.3% of the respondents
      had previous sexual exposure with higher proportions being male (p = 0.00043).
      Majorities' first sexual exposure was unplanned. Family settings and educational
      level do not have significant influence on the previous sexual exposure. The
      methods of sexual activity were mainly through vagina route while some had also
      practiced oral and anal sex. Most of those that are sexually exposed had more
      than one partner. About half of the respondents learn about sex from their
      friends while others through their parents and media. We conclude that in-school
      adolescents practiced unsafe sexual activity and they are therefore predisposed
      to STI/HIV and other reproductive health risks.

PMID- 20695045
TI  - Social context of premarital fertility in rural South-Africa.
AB  - A qualitative study was conducted in Agincourt, a rural area of South Africa, to
      document the perceptions and attitudes towards premarital fertility and late
      marriage among young adults of both sexes. Two focus groups and 35 individual
      interviews were conducted among 17-30 year olds, randomly selected. Most
      interviewees perceived premarital fertility as undesirable, and a new phenomenon
      in a context of major social changes, in particular loss of authority of parents
      and increasing freedom of the youth. In contrast, late marriage was perceived as
      positive, by both sexes, primarily for economic reasons. Much stigma was
      associated with premarital fertility, from friends, institutions and families who
      occasionally apply mild or severe sanctions. Consequences of premarital fertility
      were numerous: school abandonment, economic adversity, health risks,
      stigmatization. In extreme cases, premarital fertility might lead to exclusion
      and deviant behavior. Premarital fertility was ultimately due to a lack of
      contraception among young women, and to refusal of abortion for religious
      reasons, and is associated with the risk of contracting STD's.

PMID- 20695046
TI  - Sexual abuse among juvenile female street hawkers in Anambra State, Nigeria.
AB  - Street hawking exposes young girls to all forms of hazards, including sexual
      abuse. This descriptive study examines the size of the problem and the
      consequences of sexual abuse on juvenile female street hawkers randomly recruited
      from two urban towns in Anambra State of Nigeria. Data was collected with semi
      structured, interviewer administered questionnaires. The mean age of the female
      hawkers was 13.0 +/- 2.2 years. Out of 186 respondents, 130 (69.9%) had been
      sexually abused with 32 (17.2%) having had penetrative sexual intercourse (28.1%
      were forced and 56.3% submitted willingly) while hawking. Majority (59.4%) of the
      sexual partners were adults. Other types of sexual abuse experienced include
      inappropriate touches (106 cases; 81.5%) and verbal abuses (121 cases; 93.1%).
      There was low awareness of the twin risks of pregnancy (43.1%) and sexually
      transmitted infections (54.3%) following sexual abuse among the respondents.
      Sexual abuse of young female hawkers is an issue of great public health
      importance. Poverty alleviation, health education and protective child right
      policies will decrease its prevalence and the associated risks.

PMID- 20695047
TI  - Qualitative study on maternal referrals in rural Tanzania: decision making and
      acceptance of referral advice.
AB  - The aim of this study was to describe perceptions of maternal referrals in a
      rural district in Tanzania. Focus group discussions (FGDs) with health workers
      and community members, stratified by age and gender, were conducted. The FGDs
      revealed that husbands and relatives are the decision makers in maternal
      referrals, whereas the women had limited influence, especially on emergency
      referrals. The process in deciding to seek referral care is envisaged within
      community perception of seriousness of the condition, difficulty to access and
      cost involved in transport, living expenses at the hospital, and perceived
      quality of care at facility level. The hospitals were seen as providing
      acceptable quality of care, whereas, the health centres had lower quality than
      expected. To improve maternal referral compliance and reduce perinatal and
      maternal morbidity and mortality, community views of existing referral
      guidelines, poverty reduction, women's empowerment and male involvement in
      maternal care are necessary.

PMID- 20695048
TI  - Is poor maternal mortality index in Nigeria a problem of care utilization? A case
      study of Anambra State.
AB  - Maternal mortality in Nigeria is unacceptably high. Some of the reasons may
      include poor socioeconomic development, weak health care system, low
      socioeconomic status of women and socio-cultural barriers to care utilization. A
      cross sectional study was carried out to assess the use of maternal services in
      Anambra State. A multi stage sampling technique was used to select 800 nursing
      mothers from the State who were interviewed on the use of maternal services
      during their last pregnancy. Over 95% of the subjects had formal education.
      Almost all the subjects (99.7%) attended antenatal clinics during their last
      pregnancy with 92.3% (646) of them making 4 or more visits before delivery. Over
      97% (680) of the deliveries took place in formal health facilities. Obviously,
      the women in the study population utilize maternal health services. The problem
      of maternal mortality in the country may not necessarily lie with utilization but
      with the quality of services.

PMID- 20695049
TI  - Prevalence of malaria at booking among antenatal clients in a secondary health
      care facility in Ibadan, Nigeria.
AB  - The prevalence of malaria parasitemia at booking was studied in 1,848 pregnant
      women in a secondary hospital in Ibadan, Nigeria. Main outcome variables were
      patent parasitemia and fever. 8.4% hadpatent malaria parasitaemia. Most clients
      (89%) with parasitemia were asymptomatic. Febrile subjects booked at an earlier
      gestational age [22.7 versus 24.2 weeks] than afebrile patients (p = 0.0052).
      Anemia was more prevalent among patients with patent parasitemia than those
      without (58.1% versus 22.6%, p < 0.0001). Malaria parasitaemia was higher among
      nulliparous women than other parity groups (p < 0.0001). Symptomatic malaria was
      associated with early booking for antenatal care and malaria parasitemia was a
      significant determinant of anemia. The prevalence of malaria parasitaemia in this
      study is much lower than in previous reports.

PMID- 20695050
TI  - Comparative evaluation of haemoglobin estimation amongst pregnant women in
      Ibadan: Hemocue - B haemoglobin analyzer versus haemiglobincyanide (standard)
      method as the gold standard.
AB  - This was a comparative crossectional study that was conducted among 557 antenatal
      women at the University College Hospital, Ibadan, Nigeria between 1st April and
      30th May 2006. The study compared the accuracy of haemoglobin estimation using an
      automated HemoCue B analyzer kit with a standard laboratory method
      (haemogloincyanide) as the gold standard. The result showed a positive
      correlation of HaemoCue haemoglobin results when compared with the standard
      methods (Pearson's correlation coefficient = 0.892; p value = 0.000). We
      concluded that the use of the automated HemoCue kit for haemoglobin estimation
      gives an objective assessment which overcomes the challenge of extra skilled
      manpower or power outages in rural areas thereby enhancing access to quality of
      care in resource poor countries.

PMID- 20695051
TI  - Cardiovascular disease risk profile tools and New Zealand--absolutely the best
      way forward.

PMID- 20695052
TI  - Let the haggling begin. Medical-loss-ratio provision stirs up debate.

PMID- 20695053
TI  - High risk, high demand. $5 billion insurance pool opening in some states.

PMID- 20695054
TI  - Irked by CMS rule quirk. IT subsidies cut by provider-number provision.

PMID- 20695055
TI  - Transparent reaction. Suppliers oppose FDA move to disclose more data.

PMID- 20695056
TI  - Harvard targets conflicts. New faculty policy includes disclosure of interests.

PMID- 20695057
TI  - Something to repeal and replace. Ongoing rhetoric is more about electioneering
      than policy discussion.

PMID- 20695058
TI  - Loads of potential.

PMID- 20695059
TI  - Ensuring success. Must focus on patients, eliminating inefficiencies.

PMID- 20695060
TI  - Reason for optimism. Key roles for states, providers, insurers a good thing.

PMID- 20695061
TI  - Foreign concepts.

PMID- 20695062
TI  - A new round of reform in U.K. Primary-care docs gain more control under revamp.

PMID- 20695063
TI  - Nurse and medical (general) practitioners.

PMID- 20695064
TI  - Bring back the NZ Family Physician.

PMID- 20695065
TI  - Battlefield acupuncture.

PMID- 20695066
TI  - Battlefield acupuncture.

PMID- 20695068
TI  - Should we give aspirins and statins to the elderly?

PMID- 20695070
TI  - Back to the future.

PMID- 20695069
TI  - A lament for art in/of medicine.

PMID- 20695071
TI  - Use of psychoactive drugs in children.

PMID- 20695072
TI  - Move to online only?

PMID- 20695073
TI  - In support of intravenous vitamin C.

PMID- 20695074
TI  - There is no scientific basis for acupuncture.

PMID- 20695075
TI  - Pharmacist prescribers.

PMID- 20695076
TI  - CXCL12/SDF-1 alpha activates NF-kappaB and promotes oral cancer invasion through
      the Carma3/Bcl10/Malt1 complex.
AB  - AIM: To determine how SDF-1 alpha/CXCR4 activates nuclear factor-kappa B (NF
      kappaB) and promotes oral squamous cell carcinoma (OSCC) invasion. METHODOLOGY: A
      lentivirus-based knockdown approach was utilized to deplete gene expression. NF
      kappaB activation was evaluated by Western blot analysis and electrophoretic
      mobility shift (EMSA). RESULTS: We show that the activation of NF-kappaB by CXCR4
      occurs through the Carma3/Bcl10/Malt1 (CBM) complex in OSCC. We found that loss
      of components of the CBM complex in HNSCC can inhibit SDF-1 alpha induced
      phosphorylation and degradation of IkappaBalpha, while TNF alpha induced IKK
      activation remains unchanged. Further, we identified a role for novel and
      atypical, but not classical, PKCs in activating IKK through CXCR4. Importantly,
      inhibition of the CBM complex leads to a significant decrease in SDF-1 alpha
      mediated invasion of OSCC. CONCLUSION: The CBM complex plays a critical role in
      CXCR4-induced NF-kappaB activation in OSCC. Targeting molecular components of the
      NF-kappaB signaling pathway may provide an important therapeutic opportunity in
      controlling the progression and metastasis of OSCC mediated by SDF-1 alpha.

PMID- 20695077
TI  - Human papillomavirus as an independent predictor in oral squamous cell cancer.
AB  - AIM: There is an increasing evidence for the role of high risk human
      papillomavirus (HPV) in the pathogenesis of oral squamous cell carcinoma (OSCC).
      The purpose of this study is to evaluate the relevance of HPV infection to the
      survival and prognosis of OSCC. METHODOLOGY: Fifty-two patients with OSCC were
      followed from 4 to 88 months with a median of 50.7 months. HPV DNA was identified
      in formalin-fixed, paraffin-embedded tumor specimens by nested PCR with MY09/MY11
      and GP5+/GP6+ primer pairs and the HPV genotype was determined by direct DNA
      sequencing. Association between the HPV status and risk factors for cancer as
      well as tumor-host characteristics were analyzed. Survival curves were calculated
      by the Kaplan-Meier method and analyzed using the log-rank test. RESULTS: HPV was
      found in 40.4% of the tumors with HPV16 accounting for 63.5%, HPV18 for 30.8%,
      HPV6 for 3.9% and HPV11 for 1.8%. No infection with more than one HPV genotype
      was detected. HPV infection was significantly associated with poor histological
      grade, TNM stage I-II, alcohol usage and no smoking status. Multivariate analysis
      showed that HPV had an independent prognostic effect on the overall survival
      after adjusting other confounding factors such as histological grade, TNM stage
      and tobacco usage. The presence of HPV was significantly correlated with a better
      survival in patients with OSCC. CONCLUSION: HPV infection can act as an
      independent predictor for the survival and prognosis of OSCC.

PMID- 20695078
TI  - Simulated microbe removal around finger rings using different hand sanitation
      methods.
AB  - AIM: It is our opinion that the CDC and the WHO have underestimated cross
      contamination under examination gloves in dental clinics while wearing jewelry,
      such as finger rings. These agencies only "recommend" removing jewelry, and only
      washing hands for 15 seconds with soap and warm water before donning gloves. This
      study examined several washing procedures and finger rings using simulated
      microbes. METHODOLOGY: A gloved rubber hand manikin was made and fitted with a
      fresh disposable vinyl glove. Four fingers were fitted with rings or no ring,
      dusted with simulated microbes, and washed with a scrub brush for 5, 15, and 25
      seconds under 20 degrees C and 40 degrees C water alone, or with liquid hand
      soap. Light levels (in lux) of fluorescent powder before and after washing were
      measured and delta scores calculated for changes in light levels, equivalent to
      effectiveness of hand washing procedures. A full-factorial, 3-factor analysis of
      variance (ANOVA) was used to test for differences among levels of the three study
      factors-time, temperature, and soap use. Tukey's post hoc honestly significant
      difference (HSD) test was applied to significant factors to examine pair-wise
      differences between factor levels. RESULTS: It was found that the longer the
      hands with rings were washed with a scrub brush under flowing water, the more
      simulated microbes were removed. By 25 seconds, all methods were essentially the
      same. Simulated microbes were more difficult to remove from the palm compared to
      the back of the hand. The liquid hand soap used in this study was more effective
      with warm water than cold. When given a choice of washing with cold water up to
      15 seconds, it would be preferable not to use soap to remove simulated microbes.
      Qualitatively, the outer surface of finger rings were more effectively cleaned
      than the crevice below the ring, and the ring with a stone setting appeared to
      accumulate and retain simulated microbes more than other rings. CONCLUSION: The
      most effective treatment was washing with warm water and liquid soap. Longer
      times were more effective. Rings should not be worn under examination gloves due
      to difficulty cleaning in the crevice under the ring, and the well-known
      consequences of cross-contamination between the patient and the health care
      worker.

PMID- 20695079
TI  - Expression of bone-related genes in bone marrow MSCs after cyclic mechanical
      strain: implications for distraction osteogenesis.
AB  - AIM: Understanding the response of mesenchymal stem cells (MSCs) to mechanical
      strain and their consequent gene expression patterns will broaden our knowledge
      of the mechanobiology of distraction osteogenesis. METHODOLOGY: In this study, a
      single period of cyclic mechanical stretch (0.5 Hz, 2,000 microepsilon) was
      performed on rat bone marrow MSCs. Cellular proliferation and alkaline
      phosphatase (ALP) activity was examined. The mRNA expression of six bone-related
      genes (Ets-1, bFGF, IGF-II, TGF-beta, Cbfa1 and ALP) was detected using real-time
      quantitative RT-PCR. RESULTS: The results showed that mechanical strain can
      promote MSCs proliferation, increase ALP activity, and up-regulate the expression
      of these genes. A significant increase in Ets-1 expression was detected
      immediately after mechanical stimulation, but Cbfa1 expression became elevated
      later. The temporal expression pattern of ALP coincided perfectly with Cbfa1.
      CONCLUSION: The results of this study suggest that mechanical strain may act as a
      stimulator to induce differentiation of MSCs into osteoblasts, and that these
      bone-related genes may play different roles in the response of MSCs to mechanical
      stimulation.

PMID- 20695080
TI  - The effect of funding cuts on the utilization of an oral pathology diagnostic
      service.
AB  - AIM: To examine what impact the loss of funding had on the utilization of the
      oral pathology service. METHODOLOGY: Biopsy records were retrieved and examined
      in the two year period before and after the elimination of the subsidies in 2003.
      RESULTS: After the loss of funding, there was a 31% decrease in the number of
      specimens submitted from practitioners in private practice, with the greatest
      drop noted in submissions from endodontists. CONCLUSION: Despite the immediate
      decrease in the number of biopsies submitted after the introduction of fee-for
      service, the number of specimens being submitted appears to be on the rise again,
      as practitioners appear to recognize the value of a specialized oral pathology
      diagnostic service.

PMID- 20695082
TI  - CLS managers' role in the profession.

PMID- 20695081
TI  - Fluconazole susceptibility and genotypic heterogeneity of oral Candida albicans
      colonies from the patients with cancer receiving chemotherapy in China.
AB  - AIM: To identify heterogeneity of Candida albicans (C. albicans) isolated from
      the population with cancer in China by using identification medium, subculture
      molecular typing, and antifungal susceptibility test. METHODOLOGY: Oral cheek
      mucosal specimens from 52 cancer patients receiving chemotherapy were cultured on
      CHROMagar Candida plates for Candida identification. All the C. albicans colonies
      on the plates were subcultured and reconfirmed by API20C, then submitted to the
      antifungal drug susceptibility test with fluconazole and molecular typing using
      randomly amplified polymorphic DNA-PCR (RAPD) with primers RSD6 and RSD12.
      RESULTS: 54% (28/52) patients were oral yeast carriage in which C. albicans
      predominated. More than 7 C. albicans colonies were isolated from each of 12
      patients (Group A), while less than 5 colonies were isolated from each of 16
      patients (Group B). RSD6 and RSD12 were successful in eliciting 17 (A1-A17) and 2
      (B1-B2) genotypes, respectively from among the 205 isolates. The two primers were
      combined to generate 21 genotypes. The C. albicans isolates obtained from the
      same patient and episode showed a diversity for fluconazole revealed by MIC50 and
      MIC90. CONCLUSION: The heterogeneity of the C. albicans colonies isolated from
      the same patients can be detected. C. albicans with varied fluconazole
      susceptibility and genotypic characteristics may coexist in the same oral Candida
      population.

PMID- 20695083
TI  - Intravenous vitamin C.

PMID- 20695084
TI  - DH raises cost-cuts target by a third.

PMID- 20695085
TI  - Lansley challenges a decade of NHS spending. Interview by Alastair McLellan.

PMID- 20695086
TI  - NHS executive pay.

PMID- 20695087
TI  - Gimme 5: why this price is right.

PMID- 20695089
TI  - Change dynamics: Our mutual trends.

PMID- 20695088
TI  - A new interaction.

PMID- 20695090
TI  - Roundtable: The do better dynamic.

PMID- 20695091
TI  - Interaction with individuals: Driving with dual controls.

PMID- 20695092
TI  - Interaction with the public: So we all know where we are.

PMID- 20695093
TI  - Community involvement: Popular ideas.

PMID- 20695094
TI  - Self management: Best in the long term.

PMID- 20695095
TI  - Shared decision making: A decisive improvement.

PMID- 20695096
TI  - Efficiency: Essential items for your recession survival kit.

PMID- 20695097
TI  - Innovation: How to drive quality from pilot to practice.

PMID- 20695098
TI  - Government policy: It's public health, Jamie, but not as we know it...

PMID- 20695099
TI  - Lansley's plan: DH forced to rethink vision.

PMID- 20695100
TI  - How the third sector will save the NHS.

PMID- 20695101
TI  - Unhealthy? Then help yourself.

PMID- 20695102
TI  - Commissioning: part 1 of 2. Ideal decisions for well defined areas.

PMID- 20695103
TI  - Service design: Home is where the heart of significant savings is.

PMID- 20695104
TI  - Medical publishing. Will paper live on?

PMID- 20695105
TI  - Love song.

PMID- 20695106
TI  - Re "A fatal zest for living".

PMID- 20695107
TI  - Hospitals face shortfalls as emergency demand spirals.

PMID- 20695108
TI  - Has Lansley called time on falling waiting lists?

PMID- 20695109
TI  - GPs in the hotseat.

PMID- 20695110
TI  - The bones of a PCT recovery plan.

PMID- 20695111
TI  - Innovation: An uninterrupted flow of ideas.

PMID- 20695112
TI  - GOP looks to get even. Berwick appointment may be trouble for Obama.

PMID- 20695113
TI  - PhRMA's new chief. Castellani seen as coalition builder, but some skeptical.

PMID- 20695114
TI  - Preventive approval. Insurers, rest of industry applaud free screenings.

PMID- 20695115
TI  - Is RAC ready to roll?

PMID- 20695116
TI  - Emory, HCA to end venture. Cultural differences, control cited as obstacles.

PMID- 20695117
TI  - Tactical decisions. How clinic chain adopted EHR, quality tracking.

PMID- 20695118
TI  - Slow growing.

PMID- 20695119
TI  - Data trackers. Fifteen firms provided compensation data on wide variety of
      specialties.

PMID- 20695120
TI  - Just add nine zeroes. Billion-dollar hospital construction projects becoming
      commonplace.

PMID- 20695121
TI  - Contract investigators.

PMID- 20695122
TI  - On the habits of transposons: Dissociation mapping in maize and megabase
      sequencing in wheat reveal site preferences, distribution, and evolutionary
      history.

PMID- 20695123
TI  - Re "Consultations ... going, going, gone?".

PMID- 20695124
TI  - A wake-up call.

PMID- 20695125
TI  - Withdrawn: Norelgestromin/ethinyl estradiol transdermal system.

PMID- 20695126
TI  - Mental health status and use of mental health services by California adults.
AB  - In 2005, nearly one in five adults in California, about 4.9 million people, said
      they needed help for a mental or emotional health problem. Approximately one in
      25, or over one million Californians, reported symptoms associated with serious
      psychological distress (SPD). Of those adults with either perceived need or SPD,
      only one in three reported visiting a mental health professional for treatment.
      This policy brief, based on data from the 2005 California Health Interview Survey
      (CHIS 2005), presents the first comprehensive overview of mental health status
      and service use in California, and highlights differences by age, gender,
      race/ethnicity, income and insurance status. It also demonstrates the critical
      need for continued efforts to expand mental health services and threats to such
      services caused by the ongoing state budget crisis.

PMID- 20695127
TI  - TRICARE; extended care health option. Final rule.
AB  - The Department of Defense is publishing this final rule to implement the
      requirements enacted by Congress in Section 732 of the Duncan Hunter National
      Defense Authorization Act for Fiscal Year 2009 which changes the limit of the
      Government's share of providing certain benefits under the Extended Care Health
      Option (ECHO) from $2,500 per month to $36,000 per year, and for other non
      legislated changes to the ECHO.

PMID- 20695128
TI  - TRICARE; elimination of voluntary disenrollment lock-out. Final rule.
AB  - This final rule eliminates the 1 year lock out for non-Active Duty members who
      disenroll from TRICARE Prime before their annual enrollment renewal date.

PMID- 20695129
TI  - [Successful resection of locally advanced gastrointestinal stromal tumor of the
      ampulla of Vater after treatment with imatinib].
AB  - Gastrointestinal stromal tumor (GISTs) are the most common mesenchymal tumors of
      the gastrointestinal tract arising from Cajal's cells, expressing CD 117. The
      standard treatment for primary GIST is complete surgical resection. Imatinib
      mesylate, a specific tyrosine kinase inhibitor, is effective against locally
      advanced and metastatic GIST. There are several reports of the effect of
      preoperative imatinib in patients with unresectable and locally advanced primary
      GIST. We report a case of unresectable primary GIST of the ampulla of Vater,
      which we were able to completely resect after treatment with a dosage of imatinib
      400 mg daily for 5 months. Twelve months later, the patient was treated with
      imatinib and doing well with no evidence of recurrence.

PMID- 20695130
TI  - [A case of hemophagocytic syndrome in an ulcerative colitis patient].
AB  - A case of hemophagocytic syndrome associated with ulcerative colitis is very
      rare. A 32-year-old man visited the hospital complaining of fever and severe
      abdominal pain for 7 days. He was diagnosed to have ulcerative colitis 2 years
      ago and had been treated with sulfasalazine. Three months ago, he had abdominal
      pain, weight loss, and hematochezia, so prednisolone and mercaptopurine were
      added to the treatment. On admission, the physical examination showed
      splenomegaly. Peripheral blood counts revealed pancytopenia, and bone marrow
      aspirate smears showed many histiocytes with active hemophagocytosis. There was
      no evidence of viral and bacterial infections and other neoplasms, which were
      commonly associated with hemophagocytic syndrome. He was successfully treated
      with high dose steroid. We report this case along with a review of the related
      literatures.

PMID- 20695131
TI  - Hematopoietic stem cell transplantation. Introduction.

PMID- 20695132
TI  - Skin cancer after organ transplantation. Foreword.

PMID- 20695133
TI  - [The Susy Safe project: an international initiative aimed at preventing choking a
      caused by foreign bodies in children: invitation to participation].

PMID- 20695134
TI  - [Orthopedics, traumatology, surgery and the current concept of musculoskeletal
      trauma care].

PMID- 20695135
TI  - Promoting and prioritizing reproductive health commodities: understanding the
      emergency contraception value chain in South Africa.
AB  - Use of emergency contraception is low in South Africa despite high rates of
      unplanned and unwanted pregnancies. Existing studies have demonstrated that women
      access emergency contraception from commercial pharmacies rather than from public
      health facilities at no charge. Research has also demonstrated that awareness of
      emergency contraception is a key barrier to improving uptake, especially in the
      public health sector. This study investigates the low use of emergency
      contraception in South Africa and employs a qualitative value chain analysis to
      explore the role of market and regulatory structures in creating an enabling
      environment for the supply and promotion of emergency contraception. The results
      suggest that there are several 'market imperfections' and information barriers
      impacting on the effective supply of emergency contraception to women who are
      dependent on the public health sector for their health care. Balancing commercial
      interests with reproductive health needs, it is argued, may form a crucial part
      of the solution to the low uptake of emergency contraception in South Africa.

PMID- 20695136
TI  - Birth preparedness, complication readiness and fathers' participation in
      maternity care in a northern Nigerian community.
AB  - The role of men in maternity care in Africa is understudied, despite their
      economic dominance and decision making power. In a patriarchal society like
      northern Nigeria, pregnancy and childbirth are often regarded as exclusively
      women's affairs. Using data from interviewer administered questionnaires and in
      depth interviews; we assessed birth preparedness, complication readiness and male
      participation in maternity care in Ungogo, a northern Nigerian community.
      Majority of pregnancies were unplanned (96%). Only 32.1% of men ever accompanied
      their spouses for maternity care. There was very little preparation for skilled
      assistance during delivery (6.2%), savings for emergencies (19.5%) or
      transportation during labour (24.2%). Young paternal age (adjusted odds ratio
      [AOR] = 1.5, 95% confidence interval [CI] = 1.2-2.6), formal education (AOR =
      1.9, 95% CI=1.1-3.4) and non-Hausa Fulani ethnicity (AOR=2.3, 95% CI = 1.4-3.3)
      were independent predictors of male participation in maternity care. There is a
      need to increase involvement of men in their partner's maternity care through
      peer-led, culturally-sensitive community education and appropriate health system
      reforms.

PMID- 20695137
TI  - The attitudes of Kenyan in-school adolescents toward sexual autonomy.
AB  - This was a cross-sectional study to examine the attitudes of Kenyan in-school
      adolescents towards premarital sex, unwanted pregnancies/abortions and
      contraception. Data collection was undertaken using a structured questionnaire.
      Kenyan in-school adolescents have conservative attitudes toward premarital sex,
      disagreeing that adolescent boy and girls should be left alone to satisfy their
      sexual needs. The girls had the view that boys have uncontrollable sexual
      appetites. With regards to unwanted pregnancies, the majority of the respondents
      disagreed with allowing abortions for pregnant school girls while they agreed
      that a pregnant school girl should be allowed to return to school. However, the
      majority of the girls held the view that a school boy who had impregnated a
      school girl should be expelled from school. The attitudes of the respondents to
      contraception were also largely conservative. The conservative attitudes of the
      respondents conflicts with the findings of high levels of unsafe sex and
      reproductive ill-health among Kenyan adolescents. There is need to help Kenyan in
      school adolescents to develop more realistic attitudes toward sexuality in order
      to improve their reproductive health.

PMID- 20695138
TI  - Unmet reproductive health needs and health-seeking behaviour of adolescents in
      Owerri, Nigeria.
AB  - The study examined unmet reproductive health needs and health-seeking behaviour
      of adolescents in Owerri, Nigeria. Primary information was obtained through
      questionnaire, FGDs and in-depth interviews. The adolescents were mostly
      Christians (99.6%) and Catholics (78.6%), with 66.4% living with their parents.
      Half (50.8%) of the adolescents have had sex. Contraceptive use was low, due to
      culture. Data showed that 27.2% of the ever had sex have had STIs, mostly
      gonorrhea and syphilis; 30.2% of the female adolescents have had unintended
      pregnancies, amongst who 73.3% had recurrent pregnancies and 19.6% of all the
      females have had abortion. The primary contact for health-care was patent
      medicine operators. In conclusion, more accessible and cost-effective method of
      disseminating STI/HIV information involving the use of vernacular and
      traditional/local opinion leaders should be used.

PMID- 20695139
TI  - Factors that influence attitudes and sexual behavior among constituency youth
      workers in Oshana Region, Namibia.
AB  - This survey was carried out to assess attitudes and behaviour among youth within
      four constituencies in Oshana region, Namibia and to understand to how certain
      social and cultural factors inform attitudes and influence sexual behaviour among
      the population of young people surveyed. Using a structured questionnaire, data
      were collected from a random sample of eighty young men and women between the
      ages of 15-30 years from four constituencies in Oshana region. Survey outcomes
      revealed attitudes and certain factors that are linked to sexual risk behaviour
      such as multiple sexual partnerships. Outcomes also reveal an influence of
      established socio-cultural norms on gender dynamics within relationships and a
      culture of reserve around discussions of sex and sexuality among young people.
      Stakeholder interventions should be directed towards incorporating approaches
      that address these factors as part of efforts to curb the incidence of HIV among
      young people in Namibia.

PMID- 20695140
TI  - "Not a boy, not a child": A qualitative study on young people's views on
      childbearing in Uganda.
AB  - To understand reasons for persistent high fertility rate, we explored perceptions
      and influences of fertility motivation among young people from Uganda.
      Qualitative inquiry was used, data were organised using NVivo 2 package and
      latent content analysis performed. Major themes that emerged on factors that
      entrench high fertility included "Sustenance of 'men's blood' through the male
      child"; "poverty, joblessness and child bearing", and "other socio-cultural
      issues: religion, kin, elders and child bearing". Factors that reduce fertility
      included "perception on women emancipation, job security and couple fertility
      communication". Young peoples' views on motivation for childbearing in Uganda are
      embedded in cultural norms and linked strongly to patriarchy, social
      respectability and women's sustenance. Innovative cultural practices and programs
      that increase women's social respectability such as emphasis that a girl can be
      heir and inherit her father's property are needed to reduce son-preference and
      fertility rates in the younger generation.

PMID- 20695141
TI  - Attitude towards mandatory pre-marital HIV testing among unmarried youths in
      Ibadan northwest local government area, Nigeria.
AB  - This study assessed the attitude of unmarried youths towards Mandatory Premarital
      HIV Testing (MPHT) in Ibadan Northwest Local Government Area. A three-stage
      sampling technique was used to select 571 unmarried youths from households. A
      validated questionnaire was used for the collection of the data. Descriptive, Chi
      square statistics and logistics regression were used to analyze the data. Mean
      age of respondents was 20.6 +/- 2.6 years, 52.0% were males and 52.7% had
      completed their senior secondary education. Though 82.8% believed that MPHT could
      reduce the spread of HIV, 43.8% stated that it will increase the stigma
      associated with HIV infection. Attitude towards mandatory pre-marital HIV testing
      however was positive. Males were about two times more likely to have positive
      attitude towards mandatory pre-marital HIV testing (OR = 1.507, CI = 1.067
      2.129). Positive attitude towards MPHT among study respondents offers a window of
      opportunity of undergoing HIV testing before marriage.

PMID- 20695142
TI  - Knowledge and attitudes towards cervical cancer and human papillomavirus: a
      Nigerian pilot study.
AB  - This study aimed to ascertain the knowledge and attitudes of urban and rural
      dwellers to cervical cancer and HPV in Gwagwalada Area Council of Nigeria. 400
      participants aged 15-45 years were selected from Gwagwalada town and the
      adjourning Giri village to respond to a multi-choice-free response questionnaire
      designed to obtain information on respondents' biodata, knowledge of STIs, human
      papilloma virus and cervical cancer, health and communication resources in their
      communities. This was supplemented by focus group discussions among religious and
      tribal groups within the urban and rural communities. We found a low level of
      awareness about HPV and cervical cancer which majority felt could not be
      prevented. Although awareness of STDs was high in both urban and rural dwellers,
      condom use was low. The study underscores the need for a well planned and
      implemented health communication and education program on STIs, HPV and cervical
      cancer in Nigeria.

PMID- 20695143
TI  - Integrating reproductive health and HIV indicators into the Nigerian health
      system--building an evidence base for action.
AB  - The lack of integrated M&E system makes it difficult to assess the effectiveness
      of HIV and family planning (FP) service integration. Since 2007, Nigeria
      integrated FP and HIV M&E systems. A pre-post survey compared the availability
      and use of FP-HIV integration M&E tools six months pre- and 12-months post
      integration in 71 health facilities supported by the Global HIV/AIDS Initiative
      Nigeria (GHAIN). Pre-integration, four facilities (6%) had national FP registers,
      32 (45%) had monthly aggregated FP data and 33 (46%) reported data up to national
      level. Post-integration, all (100%) facilities used national FP register with FP
      HIV integration indicators, and reported data up to national level. Sixty six
      facilities (93%) had at least one monthly supervisory visit. Average number of FP
      clients per facility referred for HIV testing increased from five in the first
      month to 15 by month 12 post-integration. Leveraging resources of HIV programs
      improved significantly the monitoring of FP-HIV services integration.

PMID- 20695144
TI  - Perceptions on the use of insecticide treated nets in parts of the Imo River
      Basin, Nigeria: implications for preventing malaria in pregnancy.
AB  - This study aimed at assessing perceptions on use of ITNs in parts of the Imo
      River Basin, Nigeria and its implications in preventing malaria in pregnancy.
      Data was collected using focus group discussions, key informant interviews and
      structured questionnaires. Results showed high awareness on the benefits of ITNs.
      Factors affecting use of ITNs included its high cost, perceptions of chemicals
      used to treat them as having dangerous effects on pregnancy, low utilization of
      antenatal care, husband's lack of interest in malaria prevention and perceptions
      that adolescent girls are at low risk of getting malaria. The implications of
      these findings include demystifying the negative perceptions on the chemicals
      used for net treatment and subsidizing the cost of ITNs to increase access. These
      findings provide important lessons for malaria programmes that aim at increasing
      access to ITNs by pregnant women in developing countries.

PMID- 20695145
TI  - Longitudinal evaluation of foetal transverse lie using ultrasonography.
AB  - The purpose of this study was to assess the risk of persistence of transverse lie
      detected earlier in pregnancy and associated predisposing factors using follow-up
      ultrasound (US). A longitudinal study was carried out from January 2004 to august
      2004 at Federal Medical centre, Lokoja, Nigeria. All singleton pregnancies, with
      ultrasound diagnosis of transverse lie, between 24-28 weeks were followed to
      term. At 24-28 weeks, 183 fetuses presented with transverse lie. Thirty seven
      were lost to follow-up; out of the remaining 146 babies, 22 persisted to term.
      Overall persistence rate was 15.1%. No identifiable predisposing factors were
      seen in 91.1%, placenta previa in 5.5%, lower segment fibroids in 2.7%, and
      ectopic kidney in 0.7%. In conclusion, transverse lie detected early in pregnancy
      is transient, and majority would convert to a longitudinal lie at term. Potential
      predisposing factors highlighted above increases the risk of persistent
      transverse lie at term, with placenta previa and lower segment fibroids being the
      major predisposing factors.

PMID- 20695146
TI  - An unusual case of cervico-cutaneous fistula.
AB  - A lady presented with 6 months of amenorrhea and cyclical menstruation through an
      opening in the abdominal wall for the same duration, following septic abortion.
      Examination and investigations revealed an extraperitoneal Cervicocutaneous
      fistula, which was excised in toto. She had an uneventful recovery and resumed
      normal periods.

PMID- 20695147
TI  - Acquired salpingo-enteric fistula--a case report.
AB  - Hysterosalpingogram a common radiological examination is routinely used in the
      investigation of infertility and sub-fertility in women. The close proximity of
      the uterus to adjacent pelvic structures results in various types of pelvic
      fistulas after pelvic disease, pelvic radiation therapy, trauma or pelvic
      surgery. The case of a 34 years old Para 0(+1) woman with a diagnosis of
      secondary infertility and booked for hysterosalpingogram as part of the routine
      work-up is presented. There was a positive history of chronic pelvic inflammatory
      disease, myomectomy and appendicectomy. The result showed evidence of
      opacification of the right fallopian tube with contrast outlining the adjacent
      large bowels.Asymptomatic pelvic fistulas maybe a silent cause of infertility,
      and association can only be stated as all other factors of infertility could not
      be convincingly ruled out.

PMID- 20695148
TI  - Intussusception in pregnancy--a rarely considered diagnosis.
AB  - Intussusception in pregnancy is rare and making a preoperative diagnosis is
      extremely difficult. The objective of this paper is to report a case of
      intussusception in a pregnant woman and to review the literature on the subject
      with a view to highlighting the peculiarities of this condition. The case file of
      a 26 year old Gravida 3, Para(0+2) lady who had appendectomy 5 years earlier and
      now presented at 33 weeks of gestation with features of intestinal obstruction
      was evaluated. Ultrasound scan showed dilated bowel loops suggestive of
      intestinal obstruction. At operation, an ileo-ileal intussusception was found
      without a lead point. Histology of the resected bowel segment showed haemorrhagic
      infarction without evidence of malignancy. Even though bands and adhesions are
      the commonest causes of intestinal obstruction in a patient that has had a
      previous abdominal surgery, possibility of other aetiological factors should
      always be considered.

PMID- 20695149
TI  - Ethical concerns in female genital cutting.

PMID- 20695150
TI  - Statistical approach for evaluation of contraceptive data.
AB  - This article will define how best to analyse data collected from a longitudinal
      follow up on contraceptive use and discontinuation, with special consideration to
      the needs of developing countries. Accessibility and acceptability of
      contraceptives at the ground level remains low and it is an overlooked area of
      research. The author presents a set of propositions that are closer in spirit to
      practical recommendations than to formal theorems. We will comment specifically
      on issues of model validation of model through bootstrapping techniques. The
      paper makes a presentation of a multivariate model to assess the rate of
      discontinuation of contraception, while accounting for the possibility that there
      may be factors that influence both a couple's choice of provider and their
      probability of discontinuation.

PMID- 20695151
TI  - Knowledge and utilization of the partograph among obstetric care givers in south
      west Nigeria.
AB  - This cross-sectional study assessed knowledge and utilization of the partograph
      among health care workers in southwestern Nigeria. Respondents were selected by
      multi-stage sampling method from primary, secondary and tertiary levels of care.
      719 respondents comprising of CHEWS--110 (15.3%), Auxiliary Nurses--148 (20.60%),
      Nurse/Midwives--365 (50.6%), Physicians--96 (13.4%) were selected from primary
      (38.2%), secondary (39.1%) and tertiary levels (22.7%). Only 32.3% used the
      partograph to monitor women in labour. Partograph use was reported significantly
      more frequently by respondents in tertiary level compared with respondents from
      primary/secondary levels of care (82.4% vs. 19.3%; X2 = 214.6, p < 0.0001). Only
      37.3% of respondents who were predominantly from the tertiary level of care could
      correctly mention at least one component of the partograph (X2 = 139.1, p <
      0.0001). The partograph is utilized mainly in tertiary health facilities;
      knowledge about the partograph is poor. Though affordable, the partograph is
      commonly not used to monitor the Nigerian woman in labour.

PMID- 20695152
TI  - Experience with conscious sedation for oocyte retrieval in Nigeria.
AB  - Conscious sedation is the most common method of pain relief used during
      ultrasound-directed transvaginal follicle aspiration (UDFA) for in-vitro
      fertilisation/embryo transfer (IVF/ETI). It is associated with minimal risks and
      facilitates early discharge following UDFA. The aim of this study was to assess
      clients' pain experience, acceptance of conscious sedation and correlates of pain
      during oocyte retrieval for in vitro fertilisation (IVF) at The Bridge Clinic,
      Port Harcourt. It was a cross-sectional survey conducted between May 1 and
      October 31 2004. Pain was assessed using a 100 mm visual analog scale (VAS).
      Clients' pain experience and correlates were evaluated using Pearson's
      correlation and the student's t-test. The mean pain score was low and the
      duration of the procedure did not significantly affect the severity of pain felt
      by the client. Most (69.0%) clients would prefer the same sedation and analgesia
      for any subsequent procedure. Conscious sedation and analgesia are one of several
      methods used to relieve pain during oocyte retrieval in IVF procedures. The
      information in this study is of value when considering the management of pain in
      patients undergoing oocyte retrieval procedures.

PMID- 20695153
TI  - Sexuality and health: a study of Tanzanian men's experiences of living with
      HIV/AIDS.
AB  - The aim of this study was to explore Tanzanian men's experiences regarding their
      health and sex life after they had been diagnosed with HIV. In-depth interviews
      were performed with a purposive sample of ten men living in an urban area in
      Tanzania and who had been HIV positive for more than one year. A phenomenological
      hermeneutic approach was used for analyzing the transcribed interviews. Three
      themes emerged from the texts; "awareness of HIV infection", "perceived and ideal
      health", and "sex life a source of happiness and caring". Living with HIV meant
      profound adjustments to daily life activities for the participants. HIV forced
      them to learn new ways of having sexual intercourse and new ways of acting as a
      man. The meaning of being a "real man" had changed from being a man with great
      sexual prowess to being a "caring man" within one relationship.

PMID- 20695154
TI  - Evaluation of cardiovascular morbidity in Nigerian women after 3 years of
      Norplant contraception.
AB  - This study was conducted to determine any cardiovascular morbidity with Norplant
      use by electrocardiography. Thirty Nigerian women seeking long-term reversible
      contraception were recruited. The clients had baseline blood pressure checks and
      electrocardiography (ECG) tracings. These were repeated at the 12, 24 and 36
      months follow-up visits and the results were analysed. The mean age of subjects
      was 32.4 +/- 3.98 years. The mean weight at pre-insertion and at the 12, 24 and
      36 months follow-up visits showed a statistically significant rise after 2 years
      (p < 0.01). The blood pressures did not show any significant changes throughout
      the period of study. There was statistically significant prolongation of the PR
      and QRS intervals at the 12 month visit; mean PR interval (seconds) pre-insertion
      0.153 +/- 0.003, and at 12 months 0.173 +/- 0.006 (P = 0.019), mean QRS interval
      (seconds) pre-insertion 0.056 +/- 0.003 and at 12 months 0.074 +/- 0.002 (P =
      0.005). After 3 years of Norplant use, prolongation of the mean QRS interval
      remained evident (p = 0.011) while mean PR interval had returned to pre-insertion
      levels. There is a tendency to prolongation of PR and QRS (ECG) intervals in
      Norplant users; accordingly, it may be prudent for clients with cardiac
      conditions showing longer ECG intervals, to consider alternative methods of
      contraception.

PMID- 20695155
TI  - Male infertility secondary to varicocele: a study of the management of 45
      patients.
AB  - Varicocele is a common condition worldwide. The aim of this five-year prospective
      study is to examine the effect of varicocelectomy on the fertility profile of
      affected men in a male infertility clinic in Benin City, Edo State. A total of 45
      men aged 16-65 years were diagnosed with varicocele during the period. Forty one
      (91.1%) had infertility while 4 (8.9%) were unmarried boys with third degree
      varicocele. Thirty seven (82.2%) consented to varicocelectomy; thirty three had
      infertility. Varicocelectomy was done through an open subinguinal approach.
      Restored testicular volume and semen quality were achieved within the first 12
      months in all but one. Among the 33 men who had infertility, the spouses of 23
      (69.7%) achieved pregnancy during the period of follow-up after varicocelectomy
      while the spouses of 10 (30.3%) had not. No major complication was recorded after
      operation. It is recommended that in subtropical Africa where there are no
      facilities for microscopic varicocelectomy and embolization, open varicocelectomy
      should be used. It is safe, effective and has much to offer.

PMID- 20695156
TI  - Obstetric hysterectomy in rural Democratic Republic of the Congo: an analysis of
      40 cases at Katwa Hospital.
AB  - The objective of this study was to determine the incidence, indication, and
      outcome of obstetric hysterectomy at an Eastern DRC rural hospital. This was a
      seven year retrospective study. The incidence was 0.28%. Mean age and parity of
      patients was 35.8 and 7 respectively. Trend to have Obstetric Hysterectomy
      increased with an age of = 35 years and parity of = 5. The main indications were
      Post-Partum Hemorrhage (PPH) (40%) and Ruptured Uterus (27.5%). Maternal
      mortality was 5% compared to 0.18% for Caesarean practiced at the same study
      period; and perinatal mortality 35.5%. Most indications could be avoided by
      improvement of Obstetric care.

PMID- 20695157
TI  - Prevalence of low sperm count and abnormal semen parameters in male partners of
      women consulting at infertility clinic in Abakaliki, Nigeria.
AB  - In order to provide an insight to the prevalence of low sperm count and abnormal
      semen parameters in suspected subfertile/infertile men in our environment, semen
      samples collected from one hundred and seventy (170) men aged 21-50 years, whose
      wives were seen at a private fertility clinic in Abakaliki, Nigeria with
      diagnosis of primary and secondary infertility (78 and 92 respectively) were
      analysed in accordance with World Health Organization guidelines. Significantly
      high proportion (70%) of the study population had low sperm count (p < 0.05) with
      significantly high defective parameters (64%). Asthenozoospermia and
      teratozoospermia were the major abnormal parameters recorded. Higher prevalence
      of oligospermia was found in the civil servants and age-group 31-40 years (74%
      and 75% respectively). Using 10(5) cfu/ml as a significant level of bacteria
      growth, the prevalence of bacteria growth was found to be 56% of which 18% were
      from normospermic semen d 38% from oligospermic semen.

PMID- 20695158
TI  - Perceptions and practices on menstruation amongst Nigerian secondary school
      girls.
AB  - This cross-sectional descriptive study was conducted amongst 550 secondary school
      girls in southeastern Nigeria to determine their perceptions, problems, and
      practices on menstruation. Majority of the students, (75.6%), were aged 15-17
      years. Only 39.3% perceived menstruation to be physiological. Abdominal
      pain/discomfort, (66.2%), was the commonest medical problem encountered by the
      respondents, although 45.8% had multiple problems. Medical problems were most
      commonly discussed with the mother, (47.1%), and least commonly discussed with
      the teachers, 0.4%. Analgesics, (75.6%), were most commonly used to relieve
      menstrual pain. Only 10% of respondents used non-pharmacologic remedies.
      Unsanitary menstrual absorbents were used by 55.7% of the respondents.
      Menstruation perceptions are poor, and practices often incorrect. A multi
      dimensional approach focusing on capacity building of mothers, and teachers on
      sexuality education skills; using religious organizations as avenues for
      sexuality education; and effectively using the Mass Media as reproductive health
      education channels are recommended towards improving adolescents' perceptions and
      practices on menstruation.

PMID- 20695159
TI  - Haemorheological changes in African breast cancer patients.
AB  - Several studies have indicated the existence of thrombo-embolic complications in
      cancer patients and that this could be associated with changes in
      heamorheological parameters. Packed cell volume (PCV), heamoglobin (Hb), relative
      plasma viscosity (RPV) and plasma Fibrinogen concentration (PFC) were measured in
      50 healthy control women, 50 age-matched women with breast cancer, and 10 women
      with histophathologically proven benign breast tumour. There were significant
      differences between the controls and breast cancer patients in all the parameters
      measured (p < 0.05). However, patients with cancer have significantly higher RPV
      and PFC (P < 0.001) respectively than controls. There was significant mean
      difference between pre and post mastectomy in fibrinogen concentration (p < 0.05)
      and this was observed over the 5-week study period. Since increased fibrinogen
      may give rise to increase fibrin formation which has been asserted as an
      independent cardiovascular risk factor for thromb-oembolic complications, African
      patients with breast cancer may well be predisposed to thrombotic complications
      during illness. The theological assessment may offer valuable benefit for the
      management and early diagnosis of breast cancer in African women.

PMID- 20695160
TI  - Age at menarche and the menstrual pattern of Igbo women of southeast Nigeria.
AB  - This study determines the age at menarche and menstrual pattern of an Igbo
      population in 12 randomly selected rural communities of Ebonyi State. Information
      on recalled ages at menarche, menstrual flow duration and cycle length was
      collected using a semi structured questionnaire over three months. 1209 women of
      reproductive age were interviewed. The mean age at menarche was 15.0 years and
      this declined over the years. The mean menstrual flow duration and cycle lengths
      were 3.3 days and 29.7 days respectively. Only 10.2% had a menstrual cycle length
      of 28 days. Account should be taken of the average length of 29-30 days in the
      rural Igbo population when calculating the expected date of delivery and in the
      family planning clinics.

PMID- 20695161
TI  - Postpartum sexual abstinence and breastfeeding pattern in Sagamu, Nigeria.
AB  - This was a prospective study involving 371 mothers. The mean age of the mothers
      was 27.5 (.3.6) years with a mean years at school (Educational years) of 11.3
      (2.9) years. All the mothers had previously breastfed at one of their infants for
      at least 6 months, while the mothers also breastfed their last child for an
      average (mean) of 10.3 (4.0) months. The overall mean of previous live births was
      1.9 (0.8). In the first month postpartum, 84.6% of the mothers abstained from
      sexual intercourse, but by the 4th-5th month the proportion had dropped to 18.1%,
      with just 2.1% of the study population abstaining from sexual intercourse at 11
      15 months post-partum. Forty seven (13.5%), 30 (8.6%) and 3 (0.9%) mothers in
      social classes 2,3 and 1 respectively have resumed sexual intercourse at 4-5
      months, while only 12 (3.4%) and 4 (1.1%) in social classes 2 and 3 respectively
      continued with sexual intercourse at 11-15 months. More mothers resumed sexual
      intercourse from 1 to 15 months post-partum when they breast fed for 6-10 minutes
      and 11-15 minutes than those who breast fed for 1-5 minutes, 16-20 minutes and 21
      25 minutes. Also more mothers within the 25-29 years age group resumed sexual
      intercourse from the first month to the fifteenth month post-partum than mothers
      in the other age groups.

PMID- 20695162
TI  - Use of modern birth control methods among rural communities in Imo State,
      Nigeria.
AB  - This paper studied the extent of utilization of Modern Birth Control Methods
      (MBCM) among rural dwellers in Imo State Nigeria. Three hundred and sixty
      households were randomly selected and data were obtained from them with the use
      of questionnaires and Focus Group Discussion. The results showed that only 30% of
      the respondents used MBCM while 57% of them used the traditional birth control
      methods. The most popular modern method was the condom (24.2%). This was followed
      by the IUD, used by only 2.5% of the respondents. Some of the identified factors
      that hindered the use of MBCM included perceived negative health reaction, fear
      of the unknown effects, cost, spouse's disapproval, religious belief and
      inadequate information. For a better understanding and utilization of MBCM, it is
      recommended that adequate educational campaign should be mounted in the rural
      areas on the advantages of MBCM. This campaign should target the men the more
      because they make the major decisions on MBCM use.

PMID- 20695163
TI  - Menstruation in rural Igbo women of south east Nigeria: attitudes, beliefs and
      practices.
AB  - Many cultures hold on to different beliefs and retain community-defined
      restrictions for menstruating women. The Igbo society of southeast Nigeria is
      rich in culture, myths and superstitions but, surprisingly no documentation
      exists on menstrual beliefs and practices among the population. This
      questionnaire-based cross sectional study supplemented with in-depth interviews
      evaluated the beliefs, myths and traditional practices associated with
      menstruation within rural Igbo communities. It revealed that the menstrual egress
      is of great significance in Igbo culture and must be disposed of carefully to
      avoid exposure to witchcraft and rituals. Some respondents observed self-imposed
      restrictions on exercises, food items, visits and sex in order to maintain
      physical and spiritual cleanliness, lessen discomfort and avoid embarrassment.
      Gynaecologists working in this region should utilize the opportunities of
      clinical consultations to discuss menstrual health issues with their female
      patients and educate them on the physiology and significance of menstruation.

PMID- 20695164
TI  - [Health sites and controlled spaces. A morphological study of quarantine
      architecture].
AB  - Taking as a chronological field the period between the black plague pandemic and
      the beginning of the bacteriological era in Europe, the Mediterranean and North
      America and other areas, this article addresses the morphology of lazarets as a
      whole, taking account of the different traditions and knowledge that influenced
      their configuration.

PMID- 20695165
TI  - [Spanish influenza in the Bahia de Todos os Santos: between science rituals and
      faith rituals].
AB  - This article aims to analyze responses of the population to the influenza
      epidemic that struck Salvador, capital of Bahia state, Brazil, in early September
      1918. From this perspective, we discuss the measures taken by health authorities,
      the defensive actions of ordinary people, and the adoption of religion-based
      practices to confront a disease hitherto considered benign and seasonal, which
      appeared with a surprising virulence at an unusual time of year. We used
      newspapers published in Salvador during the influenza epidemic as a privileged
      source for this research.

PMID- 20695166
TI  - Spain and the international scientific conferences on polio, 1940s-1960s.
AB  - The development of international health from a historical point of view has
      undergone major advances in recent times and constitutes a substantial part of
      the current agenda for historians of medicine. Within this framework, and
      focussing on a specific case study (international responses to poliomyelitis
      outbreaks in the 20th century), we explore the main actions and achievements of
      agencies such as the WHO and other private and international scientific
      organizations. Furthermore, this paper seeks to identify the Spanish presence and
      absence in these activities, their causes and consequences.

PMID- 20695167
TI  - Milk, social acceptance of a new food in Europe: Catalonia, 19th-20th centuries.
AB  - In this article we analyse the time course of the consumption of fresh milk in
      different regions of Europe between the 1870s and 1930s. Working from the case of
      Catalonia, we affirm that the increasing consumption of milk in that period must
      be especially linked to the spreading of new scientific knowledge in microbiology
      and nutrition that followed Pasteur's discoveries. We particularly highlight the
      information dissemination activities in this direction carried out by health
      sector professionals (medical doctors and pharmacists), governing local
      institutions and the milk industry. The initiatives developed by these groups
      changed people's preferences--fresh milk became accepted as a necessary food
      stuff, and demand for it increased. However, the evolution of consumption was not
      the same in all regions of Europe due to their different environmental and
      agronomic conditions.

PMID- 20695168
TI  - Popularizing right food and feeding practices in Spain (1847-1950). The handbooks
      of domestic economy.
AB  - The aim of this paper is to analyze a sample of domestic economy handbooks in
      order to assess the popularization of correct food and feeding practices in Spain
      between 1847 and 1950. With this contribution, we wish to evaluate another factor
      that would influence the Spanish food transition. We are aware that this is a
      very indirect source, given the high levels of illiteracy among women in Spain
      during the last third of the 19th century and the beginning of the 20th century.
      A further factor to be considered is the low proportion of girls attending
      school. We have analyzed the handbooks published in three periods. The first
      ranges from the last third of the 19th century to the first decade of the 20th.
      These handbooks are considered in order to provide background for a comparison
      with the works published from 1900 onwards. The second period focuses on the
      1920s and the 1930s. The last period covers the handbooks published after the
      Civil War under the monopoly of the Seccion Femenina (women's section of the
      Falange). Over the years under consideration, recommendations underwent a
      progressive modification from the very simple leaflets used in the 19th century
      to the introduction of scientific factors into the teaching of domestic
      economy.The work of Rosa Sensat represented the beginnings of this trend. A
      further modernizing factor was the appearance of vitamins in some of the
      handbooks. After the war, the number of handbooks decreased and they were, in
      general, very poor. If we consider the content on vitamins, there was a lack or
      shortage of information in comparison with some of the books published in the
      same period outside the monopoly of the Seccion Femenina. In conclusion, we can
      state that the repetition of recommendations on good feeding habits and the
      increase in girls attending school would exert a positive influence on the food
      transition of the Spanish population.

PMID- 20695169
TI  - [The prehistory of mathematics and the modern mind: mathematical thought and
      resourcefulness in the Palaeolithic Franco-Cantabrian region].
AB  - In the present article, we begin by reviewing the different types of symbolic
      records produced by prehistoric groups from the oldest probable origins of the
      modern human mind. Next, we review some of the most outstanding prehistoric
      pieces related to counting, enhancing the relevance (both quantitatively and
      qualitatively) of this type of piece in the Franco-Cantabrian region. These
      reviews lead us finally to note the tremendous relevance, within this context, of
      four horse-bone plaques from the Altamira Cave, dated in the Solutrean period
      (18,500 years). These small plaques, apparently constituting a coherent group of
      interrelated elements, are proposed here as the representation of a recursive
      process, recursion being a feature proposed as proper and exclusive of human
      language.

PMID- 20695170
TI  - [Scholarships for a science in crisis: the JAE as sponsor for macroscopic anatomy
      (1912-1931)].
AB  - Beside the creation of national research institutions, the patronage work of the
      JAE (through scholarships and recognition given to Spanish scientists in the
      first third of the 20th century) was important in opening the door to the silver
      age of Spanish science. In the morphologic sciences, macroscopic anatomy was an
      almost closed science and in crisis with regard to the microscopic sciences and
      embryology. Despite this setting, the JAE chose to promote this science,
      importing European anatomical pedagogy and including the technologies and
      philosophy of the new dynamic anatomy under way on the continent. In this paper,
      we analyze the grantholders listed in the JAE archives and the studies that they
      published by them. We conclude that the utilization of these grants played an
      important role in promoting the international exchange necessary for the reform
      of a science in crisis, with anatomical pedagogy and technology being the major
      protagonists of this renewal.

PMID- 20695171
TI  - [The "Chapter on health preservation" in the Kitab al-taysir fi l-mudawat wa-l
      tadbir by Avenzoar (1095-1162)].
AB  - The Kitab al-taysir fi l-mudawat wa-l-tadbir (The Method of Preparing Medicines
      and Diet) was written in Arabic by Avenzoar (1095-1162). It has yet to be
      translated into any Western modern language, and we wish to take on this task. We
      begin by offering an annotated Spanish translation (with commentary) of its
      preliminary "Chapter on the preservation of health". The Al-mohad caliph 'Abd al
      Mu'min, for whom Avenzoar served as court physician, requested the book for his
      personal use. The work begins with this chapter, which contains measures for
      preventing and curing certain diseases. This section is followed by the main body
      of the book. It consists of a complete list of diseases working from head to toe
      and including their description, symptoms and treatment. The translated chapter
      is an atypical and concise treatise on the subject. It is presented in a quasi
      aphoristic style that appears to have been used by Avenzoar to rapidly deal with
      the prevention area, in order to concentrate his efforts on what is surely one of
      the finest and most extensive mediaeval nosographies. We make this claim because
      our author does not exclusively use for this purpose the so-called "non-naturals"
      -the usual focus of health preservation measures of the time. Rather, he makes
      wide use of simple medicines with preventative ends--an unusual practice.
      Moreover, he indiscriminately intersperses prevention elements with others that
      are intended to cure. In order to better understand the meaning of this text, we
      previously refer to the foundations of health preservation practices in the
      mediaeval world, to the reasons why Avenzoar wrote the Kitab al-taysir fi l
      mudawat wa-l-tadbir, and to the characteristics of its translated chapter. We
      also examine the medical sources and contents of this chapter.

PMID- 20695172
TI  - [My colleague and friend Juan Antonio Paniagua, historian of medicine].

PMID- 20695173
TI  - Trepanation and Roman medicine: a comparison of osteoarchaeological remains,
      material culture and written texts.
AB  - Evidence for prehistoric trepanation is limited to preserved osteoarchaeological
      material, namely human skulls, and the occasional discovery of surgical
      instruments. However, the Roman empire gave rise to an abundant and diverse range
      of source types, including skeletal remains, material culture and detailed
      medical texts, each of which harbours the potential to contribute to our
      understanding of trepanation during this historical period. This paper highlights
      the advantages and inherent biases of each of these source types, and proposes
      that the simultaneous analysis and integration of different types of historical
      evidence is essential for the study of trepanation as a surgical procedure.

PMID- 20695174
TI  - A brief history of malaria chemotherapy.
AB  - Malaria is one of the worst sicknesses to affect humankind. For centuries there
      was no specific treatment, and it was not until the seventeenth century that
      Spanish colonisers brought back from Peru tree bark from which quinine was later
      extracted. In the twentieth century, synthetic alternatives to quinine were
      developed. Of these, chloroquine was the most successful, but by the 1970s
      widespread resistance had developed and the world was left without an effective
      treatment for malaria. During the same decade Chinese scientists extracted from
      sweet wormwood plant the drug artemisinin, which has proved to be very effective
      against chloroquine-resistant malarial parasites. The use of a combination
      therapy including artemisinin has made it possible to contemplate the eradication
      of malaria. Efforts to produce a stable and inexpensive supply of artemisinin are
      under way.

PMID- 20695175
TI  - The Maclagan family: six generations of service.
AB  - The Maclagans were a Scots family from humble origins who produced famous
      physicians and surgeons (two of them presidents of Royal Colleges), ministers of
      religion (including one archbishop and several missionaries), a director of the
      Victoria & Albert Museum, a famous anthropologist, many army officers, a leading
      Oxford historian, several town mayors and politicians. Their lasting legacies
      include many books, papers and reports, new university departments and degrees, a
      new and much-needed focus on public health and hygiene, the care of the mentally
      ill and the development of military medicine, as well as a heightened reputation
      for the Royal College of Physicians of Edinburgh and the Victoria & Albert
      Museum, all seemingly achieved without thought for personal aggrandisement.
      People who knew the Maclagans well characterised them by their energy, vision,
      graciousness, humour and commitment to serving others and their Christian faith.

PMID- 20695176
TI  - Redi's denial of spontaneous generation in insects.

PMID- 20695177
TI  - William Porterfield (1696-1771).

PMID- 20695178
TI  - [An assessment of the sympathetic function within the hand in patients with
      partial laceration of the median nerve].
AB  - The objective of this study was an assessment of sympathetic activity within the
      hand in patients with traumatic, incomplete nerve lacerations. In 12 patients, 1
      female and 11 male in the mean age of 30 years with injuries of these nerves
      within forearm, the sympathetic skin response was obtained with index fingers of
      the affected and unaffected hand. Capillaroscopy examination of nail folds of the
      middle fingers was performed in affected and unaffected hand. Over and above,
      symptoms and signs attributed to the sympathetic function were registered.
      RESULTS: Mean values of the sympathetic skin response parameters: amplitude and
      area were statistically significantly reduced in the affected hand, comparing to
      the unaffected: amplitude 0.5 vs 1.0 mV, area 0.6 vs 1.2 mVms, respectively.
      Latency was not different between the hands; 1.4 vs. 1.5 ms. Qualitative analysis
      of the SSR graphs revealed no response in two patients, reduced SSR in 7 and
      normal SSR in 3 patients. Wide individual variability of the parameters of the
      sympathetic skin response was observed. Capillaroscopy. Mean diameters of
      afferent capillary vessels were greater in the affected (11.7 pm) than in the
      unaffected (10.7 microm) hand, but the difference was not significant. Mean
      diameters of efferent capillary vessels were statistically significantly greater
      in the affected (15.2 microm) than in the unaffected (14.2 microm) hand, what may
      be attributed to reduced sympathetic activity in the distribution of the examined
      nerve. All patients reported symptoms and signs attributed to sympathetic
      dysfunction, which majority of them were considered troublesome in their daily
      life. Results obtained in our study does not allow for a definitive conclusion
      regarding the severity of sympathetic dysfunction due to partial laceration of
      the median or median and ulnar nerves. The results indicate on limited ability of
      employed diagnostic techniques in detection of factual effect of the loss of
      sympathetic fibres in the median nerve on the activity of sympathetic system in
      the distribution of this nerve.

PMID- 20695179
TI  - [Long follow-up radiological assessment of the cemented hip prosthesis].
AB  - MATERIALS AND METHODS: The postoperative and last follow-up radiograms: 7 to 25
      years after surgery (mean: 10.4 +/- 3.9) were evaluated in 123 patients (167
      hips). The radiological evaluation was performed according to Hip Society
      recommendations. The position of the cup and the stem, polyethylene wear, the
      migration of the cup or stem, radiolucent lines and ectopic ossification were
      evaluated. RESULTS: At last follow-up in 17 hips a prior revision was performed
      and further radiological assessment revealed 16 cases of prosthesis loosening.
      The retrospective analysis of the postoperative radiograms of 33 hips with
      loosening revealed radiolucent lines around the cup in de-Lee zones I, II, III
      respectively in 5, 2, 5 hips where in patients without loosening radiolucent
      lines were found in respectively 11, 4, 17 hips. The correlation between the cup
      or stem positioning and the rate of loosening was not significant. Fracture of
      the cup cement was found in 5 hips and radiolucent line around the cup cement in
      I, II and III zone of deLee was found respectively in 70, 26, 52 hips at last
      follow-up. No polyethylene wear was found in 77 hips when mean wear of 2.9 mm was
      found in the rest. The radiolucent line was most often detected in Gruen zones 3,
      9 and 10. The ectopic ossification was found in 67% hips at last follow-up.
      CONCLUSIONS: The radiolucent line around the cup is more often detected on
      postoperative radiograms in patients with early cup loosening but this
      correlation is not so clear in stem loosning. The increased osteolysis around the
      implant as well as ectopic ossifications are found in long follow-up of the
      cemented hip prosthesis.

PMID- 20695180
TI  - [Assessment of absolute knee joint linear and angular velocity in patients with
      spastic cerebral palsy after operative treatment of lever arm disfunction
      deformities--prospective study].
AB  - INTRODUCTION: Lever arm dysfunction (LAD) deformities in patients with CP are
      based on imbalanced forces acting in lower limbs during gait. Muscle imbalance
      results in bone axial deformities, simultaneously magnifying biomechanical
      disturbances. Goal. Analysis of knee joint velocity in patients with spastic
      dipegia treated with use of single event multi level surgery (SEMLS). MATERIAL:
      15 patients (21 limbs), mean age--15 years (12-23) at operation, with spastic CP
      treated with use of SEMLS were included. In all ceases the distal derotational
      femoral osteotomy, combined with various additional operative correction were
      performed. Patients were divided into two groups depending on distal RF transfer
      as a single criteria. METHOD: Patients were examined with use of VICON 460 motion
      analysis system: before and 12 months after operative treatment. Lower limb
      joints ROM, with changed parameters of coronal and sagittal plane moments, was
      subjected to detailed analysis, with assessment of influence of mentioned moments
      on knee joint absolute LV and AV during terminal stance (TS), toe off (TO) and
      initial swing (IS). RESULTS: The statistically significant increase in knee joint
      LV in TS, TO, IS, p < 0,001, before (mean: TS--536.3 mm/s; TO--668.7 mm/s; 826.1
      mm/s) and after (mean: TS--828 mm/s; TO--1007.5 mm/s; 174.5 mm/s) treatment was
      observed and compared to normal healthy adults. The difference in knee joint AV
      was statistically significant in TS p = 0.018 (mean: before: 82.2 deg/s; after:
      81.2 deg/s) and IS p = 0.023 (mean: before: 53 deg/s; after: 20.2 deg/s).
      CONCLUSIONS: Joints moments improvement, as an outcome of operative treatment,
      resulted in increase of absolute LV and AV of knee joint towards values of
      healthy adults, consequently improving CP patients gait.

PMID- 20695181
TI  - [Arthrodesis of the lisfranc joint as salvage procedure after trauma injury].
AB  - Dislocations and fractures of the tarsometatarsal joints (Lisfranc joint) are
      rare, often non properly diagnosed and treated. Lack of proper diagnosis and
      postponed operative treatment causes painful deformity of the foot. There are
      presented results of operative treatment in 6 patients (6 feet) with
      fracture/dislocation of the Lisfranc joint. In all of them arthrodesis as
      salavage procedure was performed. Age at the fracture/dislocation ranged from 13
      to 58 years. After trauma no one was treated operatively. Injury was overlooked
      in 2 patients. Indications for arthrodesis were pain causing limping as well
      flattening and abduction deformity fo the foot. Arthrodesis was performed from 1
      to 39 years after trauma. It was closing wedge resection of the Lisfranc joint,
      stabilization with Kischner wires for 6 weeks and below knee plaster cast for 3
      months. Follow-up ranged from 14 to 52 months. Functional results in AOFAS scale
      ranged from 6 do 90 points (mean 63 points) of 100. Subjective results ranged
      from 1 to 8 points (mean 5.6 points) of 10. Two females were not satisfied with
      the results of treament.

PMID- 20695182
TI  - [Arthrodesis of the first metatarsophalangeal joint using a spherical reamer and
      titanium compression staples--preliminary report].
AB  - BACKGROUND: The role of arthrodesis of the first metatarsophalangeal joint (MTP
      I) for the treatment of many primary foot problems or as a salvage procedure is
      an well accepted procedure. In this study, authors present the results of a
      surgical technique using spherical reaming and compression with two titanium
      staples in perpendicular planes to achieve fusion. Compression across arthrodesis
      site is achieved by difference in width between holes in drill guide and width of
      titanium staple. MATERIALS AND METHODS: 27 metatarsophalangeal joint arthrodeses
      were performed in 24 patients with different forefoot deformities. The average
      age of the patients was 53 years and average followup period was 28 months.
      RESULTS: The authors obtained MTP I joint fusion in 26 treated feet within 6-12
      weeks. The mean AOFAS score was 49 points preoperatively and increased to 76
      points at last followup. CONCLUSION: Arthrodesis of the first metatarsophalangeal
      joint with spherical reaming and fixation with two titanium compression staples
      placed in perpendicular planes is a valuable and reproducible procedure for
      achieving fusion in a majority of patients.

PMID- 20695183
TI  - [The shape of the spine among children with cerebral palsy].
AB  - AIM: The objective of the study was to determine the posture among children with
      cerebral palsy referring to type of paralysis. METHODOLOGY: The research was
      performed out of 33 children with Cerebral Palsy (aged 1-18 years) who attend
      Zespol Szkol Specjalnych number 103, Accident-Orthopaedic Department in Hospital
      nr 4 in Poznan and Rehabilitation Center "Bartek" in Poznan. The questionnaire
      was used in order to check whether there is any failure curvature in cervical,
      thoracic and lumbar spine in plantar and frontal plane. The study was performed
      by visual analysis of the spine in November and December in 2007. RESULTS: (1)
      The visual analysis of the vertebral column showed that the cervical spine is
      asymmetric among two children with hemiplegia bilateralis, three with hemiplegia
      spastica and one with atetosis. (2) Among group of patients with lumbar
      hyperlordosis there are eight who are diagnosed with hemiplegia bilateralis. (3)
      These are seven patients who have the proper position of pelvis in frontal plane
      and can stand by oneself (referring to Levene's Test for Equality of Variances p
      = 0.039820). CONCLUSIONS: (1) The failure posture is common among children with
      cerebral palsy. (2) Vertebral column is asymmetrical in frontal plane among many
      patients with cerebralpalsy, especially with hemiplegia spastica. (3) The
      position of pelvis in frontal plane influence on the ability of standing by
      oneself.

PMID- 20695184
TI  - [The value of bowel preparation procedure in major orthopedic procedures
      performed in spinal anesthesia].
AB  - In common orthopedic practice the preoperative bowel preparation is used for
      orthopedic surgery made in spinal anesthesia. This procedure is done to clean
      bowel from remaining stool and enema or suppository made of laxative substance
      were used. This activity is undertaken to decrease epidemiological risk and
      streamline work of orthopedic theater. The purpose of this study was to analyze
      the value of any of the preoperative bowel preparation procedures. The study was
      performed randomly and prospective on two groups of patients, 50 patients in each
      group. The group A consisted of 50 patients who were qualified for a total hip or
      knee replacement made in spinal anesthesia and were not prepared in any way prior
      to surgery. The group B consisted of 50 patients who had any of the preoperative
      bowel preparation procedure. We evaluate the uncontrolled defecation in
      preoperative period. We have not found any uncontrolled defecation in group A
      compared with four of those cases in group B. The results allowed us to draw a
      conclusion about groundlessness of any preoperative bowel preparation procedure
      for surgery performed in spinal anesthesia.

PMID- 20695185
TI  - [Costs of surgical site infections in selected procedures in orthopedic surgery].
AB  - The aim of this work is to analyze costs of surgical site infections (SSI) in
      selected orthopedic procedures. Cases of SSI after hip and knee prosthesis
      detected in the year 2005 in the specialistic hospital situated in the southern
      Poland was taking into account in this study. CDC's definitions for detection of
      SSIs cases were used in this study. There were 22 cases of SSIs detected in the
      whole year. Estimated direct costs of additional hospitalization reached 131,000
      PLN. Costs of antibiotics used for treatment SSI cases were equal to 38 249 PLN.
      Hospital acquired infections are extremely costly side effect of hospitalization
      so their detailed and continuous surveillance is necessary. But it won't be
      possible without systemic change of management and organization of health care
      sector in Poland.

PMID- 20695186
TI  - [Orthopedic diagnostic and therapeutic problems in avascular poststeroid necrosis
      of femur head in the course acute lymphoblastic leukemia--description of 3
      cases].
AB  - INTRODUCTION: Chronic use of steroids in acute lymphoblastic leukemia is a
      significant supportive therapy. Whereas steroids have adverse effect on vessels
      leading to avascular osteonecrosis of femur head (ANFH). The aim of the study was
      to present a ANFH of three young persons diagnosed too late that ended with
      implantation of total hip arthoplasty (THA). DESCRIPTION OF CASES AND RESULTS:
      Authors described chemotherapy of acute lymphoblastic leukemia according to
      established program. The fight for patient's life finished with success, but with
      side effect--ANFH. It was not diagnosed in an early period, because diagnosis was
      based only on X-ray of the hips. According to literature pain in the hip
      accompanying negative X-ray, should be supplemented with MRI, which allows
      confirmation of oedema of femur head bone marrow. Only early decompression in I
      degree of ANFH according to ARCO classification may stop a further progress of
      disease. Pain, impairment of gait, and necrosis covering over 30% of head was an
      indication for THA. CONCLUSION: THA of hip among young people is allowed when
      joints are completely destroyed and painful.

PMID- 20695187
TI  - [Salter pelvic osteotomy in operative treatment in patients with bladder
      extrophy].
AB  - BACKGROUND: Bladder extrophy malformation includes outward rotation of the
      innominate bones, pubic symphysis diastasis and acetabular retrovertion. We have
      corrected the pelvic deformation during the reconstruction of the bladder neck
      and the urethra in older children. METHODS: From 1/01/2002 to 1/01/2006 in the
      Department of Pediatric Urology and the Department of Pediatric Orthopedics in
      Katowice 4 children were operated on for bladder extrophy. The age of the
      patients ranged from 2.3 to 4.1 years; an average of 3.6 years. In the patients
      with bladder extrophy we performed the urological reconstruction and
      simultaneously the bilateral Salter's osteotomy was done. RESULTS: The follow up
      was 52 months (48-84).The consolidation of the osteotomy was obtained in all
      patients after 62 days (48-72) with the correction of the retroversion of the
      hips and symphysis to 2.4 cm (0.9-5.8). CONCLUSION: The innominate Salter's
      osteotomy is helpful in the bladder neck reconstruction and allows to achieve the
      proper anatomy of the pelvic ring.

PMID- 20695188
TI  - 18 months of experiences with the biotitanium replacement (Implaspin) used in
      treatment of degenerative lumbar spine diseases.
AB  - Between 2007-2008 forty two patients neurosurgery department of the KNTB
      (Regional Hospital of T. Bat'a) Zlin underwent surgery using the bioactive
      replacement Implaspin. The group of 21 patient of the total of number of 42
      patients was operated first time for diagnosis degenerative instability or
      spondylolisthesis gr I-II. In this group was the follow-up period of 18 months,
      the mean baseline Oswestry score was 57%. A value of 37% was achieved after 18
      months during the evaluation of the clinical status using the Oswestry
      questionnaire. This result represented a improvement of the condition. No change
      of the position of the instruments occurred during the X-ray and CT, MRI
      controls. Therefore, the Implaspin replacement appeared to be a perfect
      alternative to other lumbar spine replacements combining the osteoconductive
      properties of the bioactive material with the rigidity of titanium.

PMID- 20695189
TI  - [HOXA11 gene expression in women with and without impaired infertility].
AB  - INTRODUCTION: HOXA genes are receptivity markers and their altered expression can
      help identify women with implantation defect. OBJECTIVES: The purpose of this
      study was to examine the expression pattern of HOXA11 and expression and
      localization of its protein product in the endometrium of women with
      endometriosis, idiopathic infertility and normal fertile patients during
      different phases of the menstrual cycle. MATERIAL AND METHODS: We evaluated
      HOXA11 mRNA level in the endometrium from endometriosis (n=36), idiopathic
      infertility (n=48) and fertile patients (n=30) during a menstrual cycle. The
      amounts of mRNA were determined by real-time quantitative PCR. Using the
      immunohistochemical techniques we compared the localization of HOXA11 protein in
      the proliferative, early secretory and midsecretory endometrium in all of the
      studied groups. Endometrial biopsy was performed by pipelle or during
      hysteroscopy. RESULTS: We observed statistically significantly elevated HOXA11
      transcripts levels in the midsecretory phase in both, the idiopathic infertility
      and the fertile control groups (p<0.05). Patients with endometriosis had low
      HOXA11 transcript level in the implantation window. Normal fertile patients
      showed statistically significantly decreased (p=0.003) HOXA11 mRNA level in the
      proliferative phase and statistically significantly increased level (p=0.018) in
      midsecretory phase, comparing to endometriosis patients. HOXA11 protein were
      localized in the nuclei of the endometrial stromal cells whereas the cytoplasm of
      these cells did not stain. CONCLUSION: Our results suggest that altered HOXA11
      gene expression in the endometrium during a menstrual cycle may be a common
      phenomenon among patients with endometriosis and may cause infertility in this
      group of patients. Further research should explain the mechanism of altered
      expression of HOXA11 gene.

PMID- 20695190
TI  - Prognostic significance of VEGF and its receptors in endometrioid endometrial
      cancer.
AB  - BACKGROUND: Angiogenesis is of crucial importance for endometrial tumor growth
      and Vascular Endothelial Growth Factor (VEGF) is the key mediator of
      angiogenesis. OBJECTIVE: The purpose of our study was to assess the prognostic
      value of VEGF and its receptors in relation to endometrioid endometrial
      carcinomas. MATERIAL AND METHODS: In this study we conducted an
      immunohistochemical evaluation of VEGF and VEGFRs expression in 84 tissue samples
      obtained from endometrioid endometrial cancer patients undergoing curative
      surgical treatment. RESULTS: Out of 84 cancers, strong positive expression of
      VEGF was seen in 35 (42%) tumors. The overall strong positive rates were 33% for
      VEGFR-1 and for 15% for VEGFR-2. There was a significant correlation between
      clinical stage and VEGF and VEGFR-1 overexpression (p=0.027 and p=0.004,
      respectively). Additionally there was a significant correlation between
      histological grade and VEGF and VEGFR-1 overexpression (p<0.001 and p<0.01,
      respectively). The 5-year DFS of patients with VEGF and VEGFR-1 overexpression
      was significantly lower than that of those with a weakly positive or negative
      tumor (p<0.001). CONCLUSION: Immunohistochemical evaluation of VEGF and VEGFR-1
      overexpression may be a useful marker for predicting 5-year DFS in endometrioid
      endometrial cancer.

PMID- 20695191
TI  - [Assessment of optoelectronic method and molecular test usefulness for cervical
      intraepithelial neoplasia and cervical cancer detection].
AB  - INTRODUCTION: Biophysics and molecular biology are disciplines dynamically
      entering the area of cervical cancer prevention. The combined test, comprising
      optoelectronic and molecular diagnostics, may play a significant role in the
      decrease of cervical cancer incidence and mortality. OBJECTIVE: Assessment of the
      combined test usefulness--optoelectronic method and HPV test for the presence of
      oncogenic HPV types, in the detection of cervical intraepithelial neoplasia and
      cervical cancer. MATERIAL AND METHOD: From August 2006 to October 2008 the study
      included 250 patients from the Laboratory of Pathophysiology of Uterine Cervix in
      Gynecology and Obstetrics Clinical Hospital of Karol Marcinkowski University of
      Medical Sciences. The patients underwent the following diagnostic tests:
      optoelectronic method, PCR test for the presence of DNA HPV HR, colposcopic
      examination and histopathologic biopsy. RESULTS: Sensitivity of the combined test
      for low-grade intraepithelial changes in the area of squamous epithelium (CIN 1)
      was 81%, while for high-grade changes (CIN 2, CIN 3) and carcinoma
      planoepitheliale together with adenocarcinoma was 100%. CONCLUSIONS:
      Optoelectronic and molecular diagnostics methods are useful in detecting
      neoplastic cervical changes. Both methods may become a key diagnostic tool of
      basic and advanced level of cervical screening. The advantage of the combined
      optoelectronic method and molecular diagnostics method over prevention based on
      cytodiagnostics and colposcopy has its source in the possibility of test
      automation and standardization.

PMID- 20695192
TI  - [Tumor necrosis factor in uterine leiomyomas at various stages of tumor growth].
AB  - OBJECTIVES: The aim of the study was to evaluate the expression of tumor necrosis
      factors -alpha and beta (TNF), their receptor and content in human uterine
      leiomyomas at various stages of tumor growth. MATERIAL AND METHODS: Studies were
      performed on human myometrium and uterine leiomyomas of various weights (small:
      less than 10 g and large: more than 100 g). Presence of both growth factors and
      their receptor was detected by Western Immunoblotting technique. The content of
      TNF-alpha was evaluated by immunoenzymatic method (ELISA). RESULTS: Changes in
      the expression of tumor necrosis factors and their receptor and difference in
      content of TNF-alpha during the tumor growth were found. CONCLUSIONS: Myometrium
      conversion into leiomyoma and an increase in its mass is accompanied by changes
      in the expression and contents TNF and TNF RI.

PMID- 20695193
TI  - [Evaluation of selected morphological markers of inflammation in afterbirth from
      idiopathic premature labors].
AB  - OBJECTIVE: To evaluate morphological markers of inflammation in afterbirth tissue
      from idiopathic premature labors, with regard to symptoms of infection in
      newborns. MATERIAL AND METHODS:  STUDY GROUP: 83 afterbirth specimens from
      spontaneous labors between 22 and 37 weeks gestation. CONTROL GROUP: 30
      afterbirth specimens from physiological labors. The histopathological examination
      included evaluation of placenta with umbilical membranes and umbilical cords from
      the abovementioned labors; next the results were juxtaposed with the incidence of
      neonatal infections. The evaluation covered sensitivity specificity, as well as
      the positive and negative predicative value of morphological markers in
      afterbirth infection as a diagnostic test for predicting the incidence of
      neonatal infections. RESULTS: 1. Morphological markers of afterbirth inflammation
      were reported in 28.9% of women giving premature birth (p<0.05). 2. Features of
      afterbirth inflammation were most frequently observed in the fetal membranes, and
      in the fetal membranes and placenta. 3. Premature disruption of the fetal
      membranes occurred in 66.7% of women with morphological markers of afterbirth
      inflammation and in 23.7% of women giving premature birth with no features of
      afterbirth inflammation (p<0.05). 4. Neonatal infection was reported in 75% of
      labors with morphological markers of afterbirth inflammation and in 5.1% of
      labors with no features of afterbirth inflammation (p<0.05). 5. Usefulness of
      confirming afterbirth inflammation for diagnosing neonatal infections:
      sensitivity 85.7%, specificity 90.3%, positive predicative value 75%, negative
      predicative value 94.9%. CONCLUSION: 1. Afterbirth inflammation occurs in 28.9%
      of all premature labors; however, the percentage differs depending on gestational
      age, from 84.2% in week 22-28 to 4.9% in week 33-37 of gestation. 2. Afterbirth
      inflammatory changes were reported in 2/3 of premature labors with premature
      disruption of the fetal membranes. 3. Identification of morphological markers of
      afterbirth inflammation has high sensitivity (85.7%) and specificity (90.3%) in
      predicting neonatal infections.

PMID- 20695194
TI  - [Physiotherapy in obstetrics].
AB  - Physical activity during pregnancy, active preparation for the delivery and
      rehabilitation after delivery are factors that can influence the quality of life
      of a woman at those stages of life. Treatment and prevention of leg edemas
      decreases the risk of hospitalization. Kinezytherapy helps pregnant women to
      prevent obesity and stay in good physical condition. Physiological changes in
      skeleton and muscle system may be the reason of pain during pregnancy and
      physiotherapy may effectively prevent it. Preparation for the delivery by
      physical activity, kinezytheraphy and respiratory exercises increase awareness
      and help a pregnant woman to participated more actively in the act of the
      delivery.

PMID- 20695195
TI  - [Influence of oncological treatment on fertility of women and pregnancy outcome].
AB  - Advances in cancer treatment of young patients have resulted in markedly improved
      survival rates and quality of life. However infertility remains to be one of
      adverse effects of anticancer therapy. Female patients who receive high-dose
      abdominal and/or pelvic irradiation or chemotherapy based on alkylating agents
      are at highest risk of developing ovarian failure. Among women whose fertility
      was not impaired during oncologic treatment, there is a significantly increased
      number of premature labors. High-dose irradiation also predisposes to low
      birthweight infants. Neither chemotherapy nor radiotherapy increase a risk of
      congenital malformations.

PMID- 20695196
TI  - [Vesicovaginal fistulas--current therapeutical strategy].
AB  - OBJECTIVES: Clinical evaluation of Latzko operation in primary and recurrent
      vesicovaginal fistulas and an update on current therapeutical strategy. MATERIAL
      AND METHODS: Evaluation of clinical efficacy has been performed in a group of 5
      patients with confirmed vesicovaginal fistulas and in 1 woman with urethrovaginal
      fistula. Prior to the operation, four patients had undergone eight fistula
      operations in our department with unsuccessful outcome. RESULTS: Fistula closure
      by Latzko operation has been achieved in 5 patients, including one patient who
      had surgery treatment repeated 3 months after the primary fistula operation. In
      total, additional Martius flap has been introduced twice. In patient, where
      fistula has been operated after 45 days since primary TVM and IVSO4 surgery
      closure therapy failed. CONCLUSIONS: Surgical treatment by vaginal approach
      offers great therapeutical efficacy in the primary and recurrent vesicovaginal
      fistulas, even in cases when previous abdominal surgical treatment had failed.

PMID- 20695197
TI  - [Laparoscopic gonadectomy for androgen insensitivity syndrome--case report].
AB  - Androgen insensitivity syndrome (AIS, Morris syndrome) is an X-linked recessive
      disorder of sexual development caused by the mutation of the androgen receptor
      coding gene (locus Xq11-q12). We present a case of a 17-year-old girl diagnosed
      because of primary amenorrhea. Her cytogenetic analysis revealed the kariotype of
      46, XY. Clinical examinations, based on the Quigley's scale, showed features of
      complete AIS. Hormonal tests brought the following results: FSH - 2.81 mIU/ml, LH
      - 13.88 mIU/ml. Testosterone value met the norm for a male individual in
      reproductive age (7.97 ng/ml). Family anamnesis revealed no episodes of genetic
      diseases. Due to the risk of neoplasia, the diagnosis was an indication for
      surgical gonads removal, which was performed laparoscopically. Histopathologic
      examination showed tubular adenoma with immature seminiferous tubules without
      spermatogenesis, and serous cysts. Patient was discharged on the next day after
      the operation in good general condition, and estrogen therapy was prescribed.
      CONCLUSION: Laparoscopy is an effective method in AIS treatment.

PMID- 20695199
TI  - [Recommendations of The Polish Society of Obstetrics and Gynaecology regarding
      omega-3 fatty acids in diet of women during pregnancy and lactation].

PMID- 20695198
TI  - [Prenatal ultrasonographic diagnosis of congenital epulis--two case reports and
      literature review].
AB  - The following work presents prenatal ultrasonographic examination of two rare
      fetal cases of epulis, among 13 792 fetuses referred to our unit due to suspected
      fetal anomalies by obstetricians (estimated prevalence 1/7000 among fetuses with
      different anomalies). Sonographic differential diagnosis, value of fetal nasal
      amniotic fluid flow assessment by color Doppler and the probability of EXIT
      procedure have been described.

PMID- 20695200
TI  - [Activity of carbohydrate metabolism enzymes in Streptomyces imbricatus,
      producing imbricin in controlled antibiotic biosynthesis].
AB  - Changes in the fermentative activity of Streptomyces imbricatus under the
      conditions of stimulated biosynthesis of imbricin with addition of a crude
      endoregulator to the medium were studied. The activity of the two main enzymes of
      the glycolysis, i. e. phosphofructokinase and fructose-1,6-diphosphate aldolase
      (aldolase) was determined and the functioning of the pentozophosphate pathway was
      estimated by the activity of glucose-6-phosphate dehydrogenase and NADP-specific
      glutamate dehydrogenase. Under the conditions of the endoregulation the increase
      of the imbricin production was observed when the level of the glucose catabolism
      either by the glycolytic pathway or by the pentozophosphate pathway was
      comparatively high, thus providing the antibiotic biosynthesis with the required
      precursors and reducing equivalents.

PMID- 20695201
TI  - [Antiviral activity of Ingavirin in experimental lethal influenza due to
      influenza virus B in albino mice].
AB  - The protective activity of Ingavirin against experimental infection caused by
      influenza B virus was studied on albino mice vs. Arbidol. Oral use of Ingavirin
      was shown to decrease the infectious titers of the virus in the animal lung
      tissue, to normalize the body weight dynamics, to lower the mortality and to
      increase the average lifespan vs. the placebo-treated animals. The activity of
      Ingavirin was higher than that of the reference drug. The results allowed to
      consider Ingavirin as a prospective agent for the treatment of influenza
      infection in humans.

PMID- 20695202
TI  - [In vitro efficacy of Ingavirin against the pandemic influenza virus
      A(H1N1/09)v].
AB  - Ingavirin was shown to be efficient in inhibition of the influenza virus strains
      A/California/04/2009 (H1N1)v, A/California/07/2009 (H1N1)v, A/Moscow/225/2009
      (H1N1)v and A/Moscow/226/2009 (H1N1)v, as well as the strains
      A/Chicken/Kurgan/05/2005 (H5N1) and A/Aichi/2/68 (H3N2) in the MDCK cell culture.
      The hemagglutinin and cytopathic activity of the influenza virus strains
      decreased at entering Ingavirin in vitro.

PMID- 20695203
TI  - [Estimation of in vitro Monclavit-1 virucide activity against influenza virus A
      (H5N1)].
AB  - The virucide activity of Monclavit-1 against the influenza virus
      A/Chicken/Kurgan/2/Russia/05 (H5N1) was investigated in the MDCK cell culture. It
      was shown that at a temperature of 14.0 +/- 1.0 degrees C Monclavit-1 in a 20
      fold dilution within an hour inactivated the cytopathic activity of the virus and
      the specific hemagglutinin generation by 100 and 87.5% respectively. In a 40-fold
      dilution it inactivated at the average by 50% both the cytopathic activity and
      the specific hemagglutinin generation. In an 80-fold dilution it inactivated the
      cytopathic activity at the average by 20%. In a 160-fold dilution it did not
      inactivate the pathogen. At a temperature of 25.0 +/- 1.0 degrees C Monclavit-1
      inactivated the influenza virus A/Chicken/Kurgan/2/Russia/05 (H5N1) by 90.0% only
      in the highest concentration.

PMID- 20695204
TI  - [Use of antibiotics in the treatment of ulceronecrotic tonsillitis due to
      vaccination by tabletted smallpox vaccine].
AB  - Clinical trials of tabletted pox vaccine revealed development of tonsillitis as a
      postvaccinal reaction in some volunteers: ulceronecrotic lesions in the tonsils,
      lymphadenitis, hyperthermia and asthenia. The main cause of the local
      inflammatory reactions was activation of the host opportunistic microflora
      including hemolytic streptococci and Staphylococcus aureus. For the treatment of
      the infectious complications systemic antimicrobials, such as benzylpenicillin,
      amoxicillin, ampicillin, cefazolin and fluoroquinolones (ciprofloxacin) in
      combination with the symptomatic therapy were used. The treatment course of 9
      days provided complete elimination of the postvaccinal reactions, the specific
      antibody generation being not affected.

PMID- 20695205
TI  - [Rational antibacterial therapy of patients with lower urinary tract injury].

PMID- 20695206
TI  - [Etiotropic drug therapy of widespread and socially significant human viral
      infections].

PMID- 20695207
TI  - [Hyphomycetes as organisms producing cyclodepsipeptides].
AB  - The review deals with cyclodepsipeptides produced by hyphomycetes. The
      cyclodepsipeptide compounds are prospective new agents for the treatment of
      diseases of the infectious and pathophysiologic nature.

PMID- 20695208
TI  - [Pathogenetically substantiated therapy of patients with virus hepatitis C,
      quality of life, and the disease outcome risk (clinical survey)].
AB  - The aspects of virus hepatitis C immunopathogenesis are discussed. The main
      attention is paid to higher production of Th1 cytokines providing active
      protection of the host from HCV. The up-to-date approaches to the therapy of
      chronic hepatitis C, described in the literature and the original ones, including
      the triple therapy with immunomodulators of various mechanisms of action, i.e.
      cycloferon (injections and tablets), galavit and derinat are presented. The
      comparative efficacy of the therapy is estimated. Cycloferon is shown to be the
      drug of choice in the treatment of patients with virus hepatitis addicted to
      narcotics. The clinical and laboratory efficacy of the metabolic hepatoprotector
      remaxol with antioxidant activity is described. Its high effictivity and
      satisfactory tolerability (side effects requiring discontinuation of the drug use
      were recorded only in 0.3% of the cases), as well as the minimal risk of no
      biochemical remission after its use allow to conseder remaxol as a highly
      efficient metabolic hepatoprotector for pathogenetic therapy of chronic
      hepatitis.

PMID- 20695209
TI  - [Impact of antiviral therapy on psychological factors, quality of life, and ego
      conception in infected patients].

PMID- 20695210
TI  - [Low-molecular regulators of polypeptide hormones receptors containing LGR
      repeats].
AB  - During the last years the low-molecular non-peptidic regulators of the
      polypeptide hormones receptors containing LGR-repeats were identified. In the
      review the data on the structure and the molecular mechanisms of action of these
      regulators as agonists and antagonists of the luteinizing, follicle-stimulating
      and thyrotropin hormones are analyzed and systematized. The regulators interact
      with the serpentine domain of LGR-receptor and trigger the signaling cascades
      coupled with the receptor. Low-molecular agonists and antagonists of the LGR
      receptors are considered as a new generation of the drugs that regulates the
      functional activity of sensitive to pituitary glycoprotein hormones signaling
      systems with high efficiency and selectivity. These regulators are more
      accessible compared to the hormones and can be use orally.

PMID- 20695211
TI  - [Molecular mechanisms of genetic damages of the myocardium in cardiomyopathy].
AB  - The review highlighted problems of reorganization of myocardical contractile and
      cytoskeletal proteins in cardiomyopathy (CM). The role of the genetic factors
      coding contractile proteins, proteins of thin and thick filaments, and also
      extracellular matrix proteins in processes of formation and development of
      hypertrophic (HCM) and dilated (DCM) cardiomyopathy are analyzed. The mechanisms
      responsible for the changes in cardiac proteins on regulation involved into force
      generation, its transfer, recycling ATP, impairments in transmembranal signals,
      that finally lead to cardiac cell dysfunction determining various manifestations
      of CM are considered.

PMID- 20695212
TI  - [A novel vector for construction of a cDNA library].
AB  - A new original vector pEM-(dT)40(f+) has been prepared. It can be used for cDNA
      library construction from polyadenylated mRNA, isolated from various sources. The
      pGEM-(dT)40f(+) is initially transformed into single stranded and then into a
      linear form and its (dT)40 tail at 3'-end is used as the vector-primer for
      synthesis of the first strand cDNA. The use of a synthetic oligonucleotide
      complementary to the vector and recombinant DNA results in vector cyclization and
      synthesis of the second strand cDNA. This approach significantly simplifies cDNA
      library construction, it does not require PCR reaction (which can induce artifact
      mutations in cDNA sequences) and restrictase treatment.

PMID- 20695213
TI  - [Antioxidant activity of vegetable oils with various omega-6/omega-3 fatty acids
      ratio].
AB  - Antioxidant activity and the oxidative stability were investigated in flax,
      sesame, silybum oils and oils with different omega-6/omega-3 fatty acid ratio.
      The content of antioxidants (AO) in crude oils and their reactivity towards
      peroxyl radicals were studied using kinetic method for addition of oil in a model
      reaction of cumol oxidation. There were correlations between PUFA/omega-9 and
      thermal stability (50 degrees C); between gamma-tocopherol content and
      resistantance to oxidative changes after storage at (10 +/- 2) degrees C for 6
      months.

PMID- 20695214
TI  - [Inhibition of adherence of Corynebacterium diphtheriae to human buccal
      epithelium by glycoside hydrolases from marine hydrobiontes].
AB  - A possibility of adhesion inhibition of Corynebacterium diphtheriae to human
      buccal epithelium by glycoside hydrolases of marine hydrobiontes was investigated
      using alpha-galactosidase from marine bacterium Pseudoalteromonas sp. KMM 701,
      total enzyme preparation and beta-1,3-glucanase from marine fungi Chaetomium,
      total enzyme preparation and beta-1,3-glucanase from marine mollusk Littorina
      kurila, and total enzyme preparation from crystalline style of marine mollusk
      Spisula sachalinensis were used. The enzymes were added to test-tubes containing
      buccal epithelial cells and/or the toxigenic bacterial strain C. diphtheriae No
      1129, v. gravis. All the investigated enzymes were able to abort C. diphtheriae
      adherence, to human buccal epithelocytes. Inhibition of adhesion was more
      pronounced in the case of treatment of epithelocytes with highly purified enzymes
      of marine hydrobiontes in comparison with total enzyme preparations. The
      significant inhibition of C. diphtheriae adhesion was observed when the enzymes
      were added to the epithelocytes with the attached microorganisms. The results
      obtained show that glycoside hydrolases of marine hydrobiontes degrade any
      carbohydrates expressed on cell surface of bacterium or human buccal
      epithelocytes, impair unique lectin-carbohydrate interaction and prevent the
      adhesion.

PMID- 20695215
TI  - [Effect of emotional painful stress on affinity of blood to oxygen, on the
      antioxidant system and physical properties of the hepatocyte microsomal
      membrane].
AB  - The emotional-painful stress causes a more pronounced decrease in affinity of
      hemoglobin to oxygen in portal blood compared with mixed blood. This contributes
      to increased oxygen pressure in hepatocytes and activates free radical processes
      in liver microsomes. Activation of lipid peroxidation is accompanied by changes
      in physical properties (microviscosity, polarity) of microsomal membranes.
      However, the increase in duration of stress treatment changes in the studied
      parameters become adaptive; this is accompanied by gradual normalization in blood
      affinity to oxygen, physical properties of membranes and the increase in
      antioxidant defence. Possible mechanisms of interaction of these systems during
      adaptation and regulation of free radical oxydation are discussed.

PMID- 20695216
TI  - [Comparative characteristics of oxygen-dependent and nitroxide-forming enzymatic
      systems of macrophages in Staphylococcus aureus and Listeria monocytogenes
      infections].
AB  - The reactivity of oxide-dependent and nitroxide-forming enzymatic systems of
      macrophages infected by bacteria, characterized by intraphagosomal
      (Staphylococcus aureus) and intracytoplasmatic (Listeria monocytogenes)
      localization in the phagocyte has been investigated. The correlation analysis
      revealed links between indices of the activity of oxide-dependent and nitroxide
      forming enzymatic systems of infected macrophages.

PMID- 20695217
TI  - [General mechanism of ozone decomposition in physiologic solutions and a method
      for evaluation of the ozone dose in solutions administered to patients].
AB  - Ozone solutions in water and in NaCl solutions found are widely used in
      technology and medicine. Some times ozone employment meets difficulties due to
      instability of ozone in solution. The paper describes the results of study of
      ozone decomposition prepared using solutions in distilled water, solutions of
      NaCl in water, including physiologic solutions from different manufacturers. Also
      it was proposed the reaction mechanisms explained influence of OH- and Cl- ions
      on the decomposition rate. Experimental follow the monomolecular law and are
      described by a straight line in Ig(Ct/C0) = f(t) coordinates. It can be used as a
      basis for a new method of evaluation of real ozone dose introduced to patients.

PMID- 20695218
TI  - [Study of peptide content of antibacterial fractions by liquid chromatography and
      mass spectrometry].
AB  - The fractions containing antimicrobic peptides have been purified from a
      haemolymph of caterpillars Galleria mellonella by chromatographic methods and
      studied by mass spectrometry.

PMID- 20695219
TI  - [Antioxidant status of patients with thyrotoxicosis syndrome treated with the
      combined regimen containing epifamin].
AB  - The work purpose was research of degree of free-radical processes intensity and
      catalase activity in blood serum of patients with a thyreotoxicosis syndrome at
      traditional treatment and the combined therapy with epifamin. Patients (n=25)
      have been divided into 2 groups: the first group of patients--12 persons who are
      on traditional treatment (antithyreoid drugs, beta-adrenoblockers); the second
      group--13 persons, are padding to basic therapy received epifamin on 1 tablet (10
      mg) 3 times a day 10-15 minutes prior to meal within 7 days. Patients with
      thyreotoxicosis syndrome had an intensification of free-radical oxidation that
      was traced at measurement of biochemiluminescence parameters in blood serum. At
      the combined therapy with epifamin less expressed intensity of free-radical
      processes, and also increasing of the general antioxidant activity of an organism
      that did not descend at traditional treatment was observed. At carrying out of
      standard therapy of thyreotoxicosis syndrome, including application of
      antithyreoid drugs and beta-adrenoblockers, catalase activity decreased, that
      unfavorable affected antioxidant potential of an organism. At the combined
      therapy with epifamin level of catalase activity, on the contrary, increased,
      that could influence positively on antioxidant protection of an organism.

PMID- 20695220
TI  - [Comparative thermodynamic analysis of thrombin interaction with anti-thrombin
      aptamers and their heterodimeric construct].
AB  - Aptamers interacting selectively with the anion-binding exosites 1 and 2 of
      thrombin were merged into dimeric oligonucleotide constructs with use of a poly
      (dT)-linker of 35 nucleotides (nt) long. Complexes of thrombin with the aptamers
      and their hetero- and homodimeric constructs were measured using the optical
      biosensor Biacore-3000. K(D) values measured for the hetero- and homodimeric
      constructs were correspondingly 25-30- and 2-3-fold lower than those for the
      primary aptamers. Analysis of temperature dependencies of K(D) values within the
      temperature interval of 10 degrees C-40 degrees C has shown that the values of
      enthalpy change deltaH upon formation of complexes of thrombin with the aptamers
      and the hetrodimeric construct are close. The value of the entropy change deltaS
      upon complex formation of thrombin with the aptamer heterodimeric construct was
      1.5-2-fold higher than deltaS values for the complexes with the aptamers. The
      complex formation and dissociation rates increased with the elevation of
      temperature from 10 degrees C to 37 degrees C. However, the dissociation rate for
      the complex of thrombin with the heterodimeric construct was evidently lower that
      that for the complexes with the aptamers.

PMID- 20695221
TI  - [Novel view of the structure of the non-catalytic N-terminal region of ATP
      dependent LonA proteases].
AB  - ATP-Dependent Lon proteases are components of the protein quality control system,
      which maintains a keeping of cellular proteome. Lon family consists of two
      subfamilies A and B, differing in subunit architecture and intracellular
      location. The reinterpretation of the domain organization of the non-catalytic N
      terminal region of ATP-dependent LonA proteases is proposed. Using Escherichia
      coli LonA protease (EcLon) as an example it has been shown that a fragment
      (alphaN-domain), which is located between the N-terminal domain and the AAA+
      module of that protein, is similar to the alpha1-domain of the first AAA+ module
      of chaperone-disaggregase C1pB. A coiled-coil (CC) region included in the alphaN
      domain of LonA is similar to the M domain of C1pB chaperones, which is inserted
      into the alpha1-domain. This region is suggested to adopt the structure similar
      to the propeller-like (PL) domain. The typical architecture of the N-terminal
      region of LonA proteases is postulated to be characterized by the obligatory
      presence of a PL domain, included in the alphaN-domain, but may vary in the
      length and topology of the preceding N-terminal domain.

PMID- 20695222
TI  - [Use of Pseudomonas bacteria strains for determining water-assimilable carbon].
AB  - The ability of 12 Pseudomonas putida and Pseudomonas fluorescens strains for
      growth in the tap water has been studied. All of them grew well in pasteurized
      Kyiv tap water at 500 colony-forming units--CFU/ml inoculum reaching the maximal
      titre 1.7 x 10(4)-4.6 x 10(6) CFU/ml after 240 hours of incubation. The most
      intensive growth was observed in strain P. putida UCM B-143, capable to
      assimilation of 84 different sources of carbon nutrition. The linear dependence
      between strain 143 growth and acetate carbon concentration in the interval of 10
      to 60 microg/l has been demonstrated in deionized water with addition of
      necessary mineral salts; its yield was 4.5 x 10(6) CFU/microg of assimilable
      acetate carbon (AOC). Determination of AOC of water using standard methods,
      standard strain P. fluorescens UCM B-385 (P17, ATCC 49642) and selected strain P.
      putida B-143 gave the similar values of AOC quantities in the Kyiv tap water (536
      and 600 microg of AOC in 11, accordingly). Viability of strain 143 grown in the
      artesian water decreased more quickly than that of the standard strain which is
      possibly connected with origin of both cultures: strain 143 was isolated from
      wheat rhizosphere while strain P17--from the drinking water.

PMID- 20695223
TI  - [Resistance to UV radiation of microorganisms isolated from the rock biotopes of
      the Antarctic region].
AB  - Microbiological analysis of terrestrial biotopes of the Antarctic Region has
      shown, that vertical rocks of the Antarctic islands open for the Sun were
      characterized by special microcenoses. The wide distribution of pigmented
      microorganisms in the rock Antarctic samples, a higher frequency of their
      occurrence, the total number and biologic diversity, than in other Antarctic
      biotopes, has been demonstrated. For the first time the presence of bacteria and
      yeast, resistant to high doses of UV radiation on the vertical rocks in the
      Antarctic Region was shown. The lethal doze of UV radiation for the Antarctic
      pink pigmented Methylobacterium strains exceeded 200-300 J/m2, for coal-black
      yeast--500-800 J/m2, for red yeast--1200-1500 J/m2. The distinctions in lethal UV
      effect against strains of Methylobacterium isolated from the regions with
      different climate have not been found. Probably, adaptation of the rock
      microcenosis to extreme factors of the environment proceeds by natural selection
      of microorganisms, which resistance to this factor is genetically determined.

PMID- 20695224
TI  - [Optimization of vermicomposting of organics enriched with phosphorites with
      participation of phosphate-mobilizing microorganisms].
AB  - Active strains of microorganisms capable to mobilize phosphorus from poorly
      soluble compounds were isolated from the vermicompost. Representatives of
      Pseudomonas genus dominate in assemblages of phosphate-mobilizing humus
      microbiota. The strains Pseudomonas sp. 17 and Pseudomonas sp. 22, which promote
      liberation of the greatest quantity of water-soluble phosphorus were selected
      under vermicomposting of organics enriched with phosphorites with participation
      of active phosphate-mobilizing microorganisms. The use of compost derived with
      participation of Pseudomonas sp. 17 in cucumbers growth technologies makes the
      plants development better and raises the cultures productivity.

PMID- 20695225
TI  - [Changes in quantity and species composition of streptomycetes associations in
      soil polluted by heavy metals].
AB  - High content of Cu, Fe, Cd, Zn, Ni mobile forms in industrial platform technozems
      of ore-concentrating factory causes a 1.5-6.3-fold decrease of microorganisms
      total quantity and 3-4 fold decrease of streptomycetes amount. The obtained
      results are confirmed by the model experience information, in accordance to which
      the streptomycetes amount decreases 1.8-2.4 times on the 1st and 10th days when
      CdSO4, Fe2(SO4)3, Ni(NO3)2, CuSO4, ZnSO4, (CH3COO)2Pb.Pb(OH) are brought in
      chernozem at the maximal concentration of heavy metals. The renewal of common
      chernozem microbiocenosis quantity under the effect of maximum possible
      concentration of heavy metals salts (MPC) is observed already on the 30th day of
      research, while at 5 MPC it is observed--after 90 days, and at 15 MPC--the
      cenosis homeostasis is violated irreversibly. The dominants of technozems
      streptomycetes association are S. albocrustosus, S. sporostellatus, S.
      sporoherbeus, S aerionidulus and S. violobrunneus. The influence of heavy metals
      blend in the industrial platform technozem results in the decline of
      streptomycetes variety in the association.

PMID- 20695226
TI  - [Effect of cultivation conditions on fatty acid content of Clavibacter
      michiganensis subsp. michiganensis lipids].
AB  - The fatty acid content of C. michiganensis subsp. michiganensis cellular lipids
      in different culture conditions was investigated. It was established, that it
      lies in a narrow range C14-C18 and belongs to isoanteiso type. The species
      character is constant, independent of temperature, duration of cultivation and
      medium content dominance of saturated branched-chain fatty acids, among which the
      anteiso-acids dominate, generally a-C15. A response to the temperature
      modification of bacteria cultivation, medium and age of culture is expressed by
      relations between separate fatty acids. Thus the modifications of fatty acid
      content, connected with age of culture and temperature of cultivation, depend on
      a strain. The cultivation of bacteria on a rich medium in comparison with poor
      one enlarges the content of nonbranched-chain and anteiso-acids in lipids.

PMID- 20695227
TI  - [Contamination of solid-cast rubber tires by microscopic fungi].
AB  - The main peculiarities of fungal resistance of two types of unit cast rubber
      tires of domestic manufacture have been investigated. Rubber tires which
      contained synthetic plasticizer were non-resistant to fungal contamination in
      contrast to ones with natural plasticizer. Using the method of confocal laser
      scanning microscopy, it was shown that inner layers of two types of rubber tires
      were contaminated with fungal mycelium. Our findings indicate that the
      investigation of microscopic fungi resistance of new materials is necessary for
      general mechanical rubber goods, especially exported to tropical climate
      countries.

PMID- 20695228
TI  - [Antiviral effect of cerium dioxide nanoparticles stabilized by low-molecular
      polyacrylic acid].
AB  - Antiviral activity of nanosize cerium dioxide sols (CeO2) in animal cell culture
      has been studied. The inhibiting effect of the mentioned sols upon reproduction
      of vesicular stomatitis test-virus was demonstrated for the first time in case of
      preliminary 24-hour contact with cells lines L929 and EPT. The effectiveness of
      protective action depends on initial precursor and the way of obtained water
      nanosize nanosols.

PMID- 20695229
TI  - [Cloning of amplicon of chromosomal SCO1206 sequences of Streptomyces coelicolor
      A 3(2)].
AB  - With the help of polymerase cycle reaction a fragment of chromosome Streptomyces
      coelicolor A 3(2) was amplified which contains gene SCO1206 coding subunit
      proteins of polyketide synthase III. Cloning of amplified DNA in the structure of
      shuttle vectors pAX5a and pWHM4 in Escherichia coli XL1 Blue was done. Plasmids
      of some selected ampicillin-resistent clones were transformed into protoplasts of
      plasmidless variant of Streptomyces globisporus 1912. Restrictional analysis of
      plasmid DNA of all investigated transformants both Escherichia coli and
      Streptomyces globisporus 1912 showed that 1.1 kb fragments of DNA were cloned in
      them. Research of the complex of metabolites, synthesized by transformants of
      Streptomyces globisporus 1912 revealed the presence of new substances which were
      not synthesized by the recipient.

PMID- 20695230
TI  - [Characteristic of one-paired pea virus].
AB  - The new virus isolated from Vicia unijuga A.Br. with filament particles with size
      1000-1200 x 10-12 nm is revealed. A thermal inactivation point is 55 degrees C;
      dilution end point - 10(-5)-10(-6) longevity in vitro in broad bean sap--less
      than one day. It is transferred by aphids and by pea, bean and broad bean seeds.
      The plants of Fabaceae, Solanaceae and Chenopodiaceae fam. were affected by this
      virus isolate. The virus yield was 40-50 mg per 100 g of leaves. The ratio of
      absorption E260/E280 corresponded to 1.4-1.5. The molecular mass of a core
      protein of the virus was 34 kD. The virus has a high immunogenic properties-
      titer is 1:256000 (indirect method of ELISA). It is presumably identified as a
      member of Closteroviridae.

PMID- 20695231
TI  - [Biofilm on a metal surface as a factor of microbial corrosion].
AB  - Main attention was given in the present review to the research methods, phases of
      biofilm's forming, exopolymer compounds of bacteria as main biofilm forming
      factor. A microbial corrosion as a result of interaction between the biofilm and
      metal surface was considered. The interaction was displayed in biomineralization.
      The future trends of biofilms study were bound with research of their
      architecture. That architecture was determined by the structure and function of
      biofilms compounds: biopolymers and biominerals.

PMID- 20695232
TI  - [Hnat Omelianovych. Ruchko (1883-1937): tragic destiny of the scientist].
AB  - The life and scientific activity of Gnat O.Ruchko, an outstanding scientist
      microbiologist, the former director of the Institute of Microbiology and
      Epidemiology are investigated. Many data and facts are represented for the first
      time, some of them are refined and corrected, since their sources are both the
      recollections of scientist's colleagues kept in the Institute archives and
      extracts from personal file trumped-up by NKVD (People's Commissariat of Internal
      Affairs) after Ruchko's imprisonment and kept in SBU (Ukrainian Security Service)
      archives. Special attention is devoted to analysis of scientist's works on
      bacteriophages, epidemiology and also to role of Gnat O.Ruchko in the Institute
      reorganization and creation of the Department of Agricultural Plants Bacterioses.

PMID- 20695234
TI  - A time of transition: Thomas Mayleigh--pharmacist or physician?

PMID- 20695233
TI  - Lapis de Goa: the 'cordial stone'.

PMID- 20695235
TI  - "Lessons of life": unconscious competent.

PMID- 20695236
TI  - The Amazonia experience: one dentist's journey to the future.

PMID- 20695237
TI  - The cult of Franz Boas and his "conspiracy" to destroy the white race.

PMID- 20695238
TI  - On alternating Boasians: generational connections.

PMID- 20695239
TI  - Boasian ethnography and contemporary intellectual property debates.

PMID- 20695240
TI  - The industry responds to the passing of healthcare reform.

PMID- 20695241
TI  - How your practice can earn $88,000 per physician over the next five years.
AB  - Your medical practice could earn as much as $88,000 per physician over the next
      five years through three new programs provided through the federal stimulus
      package. By participating in electronic health records, using electronic
      prescribing, and performing standard quality procedures that your practice most
      likely already follows, your practice could earn part of $19 billion that has
      been designated in the American Recovery and Reinvestment Act of 2009 to improve
      health information technology. You won't want to delay, however, because the
      funding is front-loaded, with of the funding provided in the first two years.

PMID- 20695242
TI  - Independent contractors versus employees: the costs and benefits for your
      practice.
AB  - Every business is interested in reducing costs. Payroll and employee benefit
      costs can be reduced through the use of independent contractors, because they are
      not employees to whom training, overtime wages, and benefits must be provided.
      Using the services of an independent contractor presents some disadvantages,
      however, as an independent contractor cannot be controlled and disciplined in the
      same fashion as an employee. There are a variety of tests applied under various
      statutes to determine whether an individual is an employee or an independent
      contractor, and it is important to carefully analyze all of the facts of a given
      situation in light of these tests before entering into an independent contractor
      relationship. If you engage an individual as an independent contractor, and that
      individual is found to actually be an employee, your business may be subject to
      significant financial penalties.

PMID- 20695243
TI  - Disruptive and toxic behaviors in healthcare: zero tolerance, the bottom line,
      and what to do about it.
AB  - In this economic downturn, healthcare leaders must attend to both the human- and
      bottom-line. Unfortunately, one significant problem affecting both-disruptive
      behaviors-has long been under the radar screen in healthcare. People who
      habitually exhibit these behaviors have been referred to in many ways: toxic,
      uncivil, and intimidating, to name a few. This article provides the results of
      the authors' research study of over 400 leaders and mitigation strategies for
      dealing with toxic, uncivil behaviors. In particular, it presents a three-point
      systems approach for intervention--one that is both proactive and reactive, and
      aligned with the new Joint Commission standards.

PMID- 20695244
TI  - Take positive steps to avoid the practice blues.

PMID- 20695245
TI  - The business end of health information technology. Can a fully integrated
      electronic health record increase provider productivity in a large community
      practice?
AB  - Electronic health records (EHRs) are expected to transform and improve the way
      medicine is practiced. However, providers perceive many barriers toward
      implementing new health information technology. Specifically, they are most
      concerned about the potentially negative impact on their practice finances and
      productivity. This study compares the productivity of 75 providers at a large
      urban primary care practice from January 2005 to February 2009, before and after
      implementing an EHR system, using longitudinal mixed model analyses. While
      decreases in productivity were observed at the time the EHR system was
      implemented, most providers quickly recovered, showing increases in productivity
      per month shortly after EHR implementation. Overall, providers had significant
      productivity increases of 1.7% per month per provider from pre- to post-EHR
      adoption. The majority of the productivity gains occurred after the practice
      instituted a pay-for-performance program, enabled by the data capture of the
      EHRs. Coupled with pay-for-performance, EHRs can spur rapid gains in provider
      productivity.

PMID- 20695246
TI  - Is it time for a new practice environment? Part II: an operational approach to
      determining space needs.
AB  - In today's practice of medicine, seeing patients requires space. The amount and
      type of space a practice needs are based on the volume of patients to be seen,
      services provided, and the number of providers in the practice. To evaluate
      whether or not your current practice space effectively houses your practice or if
      a new building could better support your practice, the amount and type of space
      the practice needs must be determined. Once this space needs assessment is done,
      it can be used to evaluate the current practice environment, and if need be
      develop preliminary drawings to evaluate new space. Both operational flow and the
      economics of creating the new improved practice (whether it is a renovation of
      existing space or brand new space) should be compared.

PMID- 20695247
TI  - Giving and receiving constructive feedback: a staff training tool.
AB  - Good feedback is rare. That is because it takes considerable time, effort, skill,
      and know-how to be able to provide and use feedback effectively. This article
      explores why feedback is a frequently misused and underused practice management
      tool. It describes the tenets of useful feedback and five common medical practice
      feedback errors. It explores the value of feedback and the particular ways that
      the medical practice staff can harness feedback to improve its work performance
      and professional skills. This article also explores the value of feedback as a
      team-building tool. It includes 15 ground rules each for receiving and for giving
      feedback. Finally, this article describes four assumptions that bad critics make
      and that members of the medical practice staff will want to avoid when giving
      feedback to their co-workers.

PMID- 20695248
TI  - Just ask: a proposal to hone the indications for sophisticated radiology
      examinations.
AB  - AIthough MRI and CT have revolutionized healthcare, the growth in their
      utilization comes with a commensurate and unsustainable growth in spending. The
      cost of sophisticated radiology tests goes beyond the cost of the technology
      itself because the tests can be so sensitive, they can lead to excessive
      treatments when incidental findings are not labeled as such. Thus to improve
      utilization for its own sake, but more importantly to limit spending on
      unnecessary treatments, we propose that requests for MRI and CT studies must be
      accompanied by a clinical question, and all reports offering interpretations must
      include a direct answer. This approach should increase the effective specificity
      of the tests that are performed, and in turn decrease provocation for unnecessary
      treatments. This question/answer policy can be implemented by new Medicare
      payment guidelines that echo the Medicare reimbursement rules for standard
      medical consultations.

PMID- 20695249
TI  - The transgender patient and your practice: what physicians and staff need to
      know.
AB  - This article describes challenges faced by transgender patients in seeking
      medical treatment and details best practices that medical practices should
      implement in order to optimize positive outcomes for their transgender patients.
      It provides an initial lexicon of terminology practitioners should use. The
      article then turns to developing cultural competence across the entire practice,
      implementing policies and practices to provide effective and appropriate
      healthcare services to transgender patients, ensuring legal compliance, and
      fostering a safe, open, and nondiscriminatory treatment environment for all
      patients. It also examines some of the specific health insurance challenges
      transgender patients face.

PMID- 20695250
TI  - ICD-10 implementation process: have a strategy that works.
AB  - This article provides background information on some of the basic elements and
      assumptions of lCD-10 and 5010 implementation. It will focus on basic
      implementation strategies that may be implemented over several months, thereby
      giving you an opportunity to fine-tune your implementation time line while
      meeting the daily demands of running your practice. We will discuss the
      importance of a team effort and of obtaining the support of physicians, billers,
      staff payers, vendors, etc.

PMID- 20695251
TI  - Patient safety: make it a priority for your organization!
AB  - Ten years have passed since the lnstitute of Medicine released its landmark
      report To Err is Human-Building a Safer Health System. Creating public awareness
      that tens of thousands of Americans were dying every year because of medical
      errors led to the establishment of multiple agencies and efforts to address this
      problem. Research on patient safety had originally focused on systems within the
      hospital setting, and now more attention is directed toward studying processes in
      the ambulatory setting (e.g., physician practices). This article reviews the
      research and other tools that are available to help leaders, executives, and
      providers create safer systems of care for patients seen throughout the physician
      practice environment.

PMID- 20695252
TI  - Branding your medical practice.
AB  - Branding is the process of differentiating your medical practice from all other
      practices in the industry. Branding takes into account the "look and feel" of
      your office, you and your staff your materials, and every other detail that gives
      your patients clues as to who you are and what you value. This article will
      review the strategies that go into building your own solid brand so your existing
      patients, as well as prospective ones, are attracted and loyal to you and your
      brand.

PMID- 20695253
TI  - Taking aim at medical identity theft. Document security key element to comply
      with government regulations.
AB  - Sensitive paper documents, such as patient records, customer data, and legal
      information, must be securely stored and destroyed when no longer needed. This is
      not only a good business practice that reduces costs and protects reputations,
      but also a legal and regulatory imperative. According to some experts, medical
      identity theft is the fastest-growing form of identity theft in North America.
      The Federal Trade Commission's Red Flags Rule, due to take effect June 1, 2010,
      requires banks; credit card companies; and, in some situations, retailers,
      hospitals, insurance companies, health clinics, and other organizations to store
      confidential personal information that can expose consumers to significant
      identity theft risks. This also includes healthcare providers and other
      organizations that are considered creditors according to their billing/payment
      procedures. This article highlights the steps healthcare providers must take to
      ensure data security.

PMID- 20695254
TI  - Five-star lessons learned: how to move up the curve in today's environment.

PMID- 20695255
TI  - Day at a time: a home care visit with Rep. Shelley Moore Capito.

PMID- 20695256
TI  - Saying goodbye.

PMID- 20695257
TI  - Whisper your way into their world: a loving and gentle approach to those with
      Alzheimer's disease.

PMID- 20695258
TI  - Alzheimer's: an overview, and its impact on our lives.

PMID- 20695259
TI  - Reciprocity: providing balanced care for those suffering from dementia.

PMID- 20695260
TI  - The little things that lead to excellence. Interview by Gerry Romano.

PMID- 20695261
TI  - Serving like a pack of wild dogs.

PMID- 20695262
TI  - Window to the world: are you OPEN for business?

PMID- 20695263
TI  - The healing mask.

PMID- 20695264
TI  - The power of caring.

PMID- 20695265
TI  - Armigeres subalbatus (Diptera: Culicidae) prophenoloxidase III is required for
      mosquito cuticle formation: ultrastructural study on dsRNA-knockdown mosquitoes.
AB  - We previously suggested that Armigeres subalbatus (Coquillett) prophenoloxidase
      III (As-pro-PO III) might be associated with morphogenesis of larvae and pupae.
      Because PO and its activation system are present in the insect cuticle, and
      cuticle formation is a major event during pupal morphogenesis, we used
      ultrastructural analysis to examine the effects of As-pro-PO III knockdown on the
      formation of pupal and adult cuticle. Inoculation of As-pro-PO III dsRNA resulted
      in the incomplete formation of nascent pupal endocuticle and pharate adult
      cuticle, i.e., significantly fewer cuticular lamellae were deposited, the
      helicoidal pattern of chitin microfibrils was disorganized, and numerous electron
      lucent spaces were present in the cuticular protein matrix. Similar disruptions
      were observed in the cuticle of adults derived from As-pro-PO III dsRNA
      inoculated pupae. It has long been suggested that the quinines, generated by PO
      catalyzed oxidation reactions, function as cross-linking agents; therefore, it
      seems reasonable to suggest that the loss of As-pro-PO III-mediated protein
      protein linkages causes morphological abnormalities in the protein matrix. Our
      findings suggest that As-pro-PO III plays a role in cuticle formation in
      mosquitoes, a novel function for phenol-oxidizing enzymes.

PMID- 20695266
TI  - Resurrection of two species from synonymy of Anopheles (Nyssorhynchus) strodei
      Root, and characterization of a distinct morphological form from the Strodei
      Complex (Diptera: Culicidae).
AB  - Anopheles albertoi Unti and Anopheles arthuri Unti are revived from the synonymy
      with Anopheles strodei Root, and a distinct morphological form (designated in
      this study as Anopheles CP Form) from the Strodei Complex of Anopheles
      (Nyssorhynchus) is characterized. The male genitalia of An. arthuri and An.
      albertoi are described and illustrated for the first time. An. strodei, An.
      arthuri, and An. albertoi were first distinguished based on scanning electron
      microphotos of the eggs, and then each egg type was associated with diagnostic
      characters of the male genitalia. Identification of Anopheles CP Form was based
      on morphological characters of the male genitalia, characterized and illustrated
      in this study. Molecular phylogenetic analysis was most clear when an outgroup
      was not included, in which case using the nuclear white gene, or the white gene
      in combination with the mitochondrial cytochrome c oxidase subunit I (COI) gene,
      clearly separated these four taxa. When Anopheles quadrimaculatus Say and
      Anopheles stephensi Liston were included as an outgroup, combined white and COI
      data resolved An. strodei and An. albertoi, whereas An. arthuri was not well
      resolved. The single sequence of Anopheles CP Form was recovered well separated
      from other groups in all analyses.

PMID- 20695267
TI  - Molecular phylogenetics of Aedes japonicus, a disease vector that recently
      invaded Western Europe, North America, and the Hawaiian islands.
AB  - We used two mitochondrial loci (nicotinamide adenine dinucleotide dehydrogenase
      subunit 4 and cytochrome oxidase II) and a nuclear locus (28S-D2 spacer) for a
      total of 1337 bp to evaluate the relationships among the four subspecies of Aedes
      (Finlaya) japonicus Theobald. Ae. j. japonicus was recently introduced into the
      United States and has been expanding rapidly. We also included in our analysis a
      morphologically very closely related species, Aedes (Finlaya) koreicus Edwards,
      as well as three more distantly related species: Aedes (Finlaya) togoi Theobald,
      Aedes (Finlaya) hatorii Yamada, and Aedes (Aedimorphus) vexans Meigen. We found
      that the four subspecies in the Ae. japonicus complex are genetically quite
      distinct but seem to form a monophyletic group that surprisingly also includes
      Ae. koreicus, suggesting the need for a taxonomic reconsideration of the group.
      We also found that the two southern subspecies are more closely related to each
      other than to any of the remaining subspecies or to Ae. koreicus and may indicate
      an ancient north-south split of the lineage. Considering the overlap between Ae.
      j. japonicus and Ae. koreicus, but the stronger association between Ae. koreicus
      and humans, we are surprised it also has not expanded from its original range. As
      a proactive reaction to this possibility, we designed and tested a DNA-based
      rapid assay to differentiate Ae. koreicus from some of the species with which it
      may be confused in the United States. These Aedes are putative vectors of several
      important viral encephalitides.

PMID- 20695268
TI  - Amblyomma triste (Acari: Ixodidae): new North American collection records,
      including the first from the United States.
AB  - New distribution records for the Neotropical tick, Amblyomma triste Koch, are
      identified from 27 specimens in 18 separate collections. These collections
      originated from six now recognized geographical foci in two states in the United
      States (Cochise and Santa Cruz Counties, Arizona, and Brewster and Jeff Davis
      Counties, Texas) and from import cattle, Bos taurus L., presented for entry at
      the United States border and originating in three Mexican states (Coahuila,
      Durango, and Sonora). For at least 67 yr, A. triste has existed in some areas of
      the United States as a cryptic species, and specimens there have been confused
      with and identified as Gulf Coast ticks, Amblyomma maculatum Koch, even by noted
      tick specialists. Most of the records reported in this study were from
      reidentified, archived specimens of putative A. maculatum.

PMID- 20695269
TI  - Stratified entomological sampling in preparation for an area-wide integrated pest
      management program: the example of Glossina palpalis gambiensis (Diptera:
      Glossinidae) in the Niayes of Senegal.
AB  - The riverine tsetse species Glossina palpalis gambiensis Vanderplank 1949
      (Diptera: Glossinidae) inhabits riparian forests along river systems in West
      Africa. The government of Senegal has embarked on a project to eliminate this
      tsetse species, and African animal trypanosomoses, from the Niayes area using an
      area-wide integrated pest management approach. A stratified entomological
      sampling strategy was therefore developed using spatial analytical tools and
      mathematical modeling. A preliminary phytosociological census identified eight
      types of suitable habitat, which could be discriminated from LandSat 7 ETM+
      satellite images and denominated wet areas. At the end of March 2009, 683
      unbaited Vavoua traps had been deployed, and the observed infested area in the
      Niayes was 525 km2. In the remaining area, a mathematical model was used to
      assess the risk that flies were present despite a sequence of zero catches. The
      analysis showed that this risk was above 0.05 in 19% of this area that will be
      considered as infested during the control operations. The remote sensing analysis
      that identified the wet areas allowed a restriction of the area to be surveyed to
      4% of the total surface area (7,150 km2), whereas the mathematical model provided
      an efficient method to improve the accuracy and the robustness of the sampling
      protocol. The final size of the control area will be decided based on the
      entomological collection data. This entomological sampling procedure might be
      used for other vector or pest control scenarios.

PMID- 20695270
TI  - Population genetic structure of the German cockroach (Blattodea: Blattellidae) in
      apartment buildings.
AB  - The German cockroach, Blattella germanica (L.) (Blattodea: Blattellidae), is a
      major residential pest with the potential to vector various pathogens and produce
      and disseminate household allergens. Understanding population genetic structure
      and differentiation of this important pest is critical to efforts to eradicate
      infestations, yet little is known in this regard. Using highly polymorphic
      microsatellite markers, we investigated patterns of genetic diversity and
      differentiation within and among 18 apartments from six apartment complexes
      located in Raleigh, NC. No departure from panmixia was found between rooms within
      apartments, indicating that active dispersal resulting in gene flow may occur
      among rooms within apartment units. Alternatively, aggregations within apartments
      may exist in relative isolation under a metapopulation framework, derived from a
      recent, common source. Thus, in the event of population control practices leading
      to incomplete cockroach eradication within an apartment, recolonization of
      shelters and rooms is likely to occur from a genetically similar aggregation. A
      pattern of isolation-by-distance across the six apartment complexes indicated
      that dispersal was more common within complexes than among them, and F statistics
      suggested greater genetic similarity between apartments in a single building than
      between separate buildings of an apartment complex. Similarly, neighbor-joining
      tree and Bayesian clustering analyses were able to cluster only those apartments
      that were within a single building, indicating higher dispersal with associated
      gene flow within buildings than between them. The lack of any broader
      connectivity, as indicated by significant F(ST) and G-tests suggests that human
      mediated dispersal of B. germanica between buildings of an apartment complex or
      between complexes occurs infrequently enough to have negligible effects on gene
      flow.

PMID- 20695271
TI  - Deep mitochondrial DNA lineage divergences within Alberta populations of
      Dermacentor albipictus (Acari: Ixodidae) do not indicate distinct species.
AB  - The winter tick Dermacentor albipictus (Packard) has a single-host life cycle
      that allows it to reach severe infestation levels on ungulates, particularly
      moose. Genotypic variation within these and related ticks has been a source of
      taxonomic confusion, although the continuity in their morphology and life history
      has generally been interpreted as indicating the existence of a single species.
      To further investigate this variation, we sequenced regions of two mitochondrial
      DNA (mtDNA) genes (COI and 16S rDNA),two nuclear genes (lysozyme and ITS-2), and
      two bacterial markers from Francisella-like endosymbionts found in these ticks
      (eubacterial mtDNA 16S rRNA and a homolog of Francisella tularensis [Dorofe'ev]
      17-kDa lipoprotein). We sampled 42 D. albipictus individuals from whitetail and
      mule deer culled from three populations in east-central Alberta, as well as four
      D. albipictus and two Dermacentor variabilis (Say) from other locations. We then
      compared DNA sequence variation between the genes and related this to variation
      in the morphology of spiracle plates. Both mtDNA regions indicated two deeply
      diverged lineages (mean difference of 7.1% for COI and 4.5% for 16S) that would
      normally be considered diagnostic of distinct species in DNA barcoding studies.
      However, very little divergence was revealed by nuclear gene sequences, bacterial
      endosymbionts, and morphometric analyses, and any variation that did occur in
      these markers was not congruent with mtDNA divergences. We conclude that the
      sampled populations in Alberta represent a single species, D. albipictus, and
      reiterate the importance of integrative approaches in species delimitation.

PMID- 20695272
TI  - Repellency to Stomoxys calcitrans (Diptera: Muscidae) of plant essential oils
      alone or in combination with Calophyllum inophyllum nut oil.
AB  - The repellency to female Stomoxys calcitrans (L.) (Diptera: Muscidae) of 21
      essential oils (EOs) alone or in combination with Calophyllum inophyllum L.
      (Clusiaceae) nut oil (tamanu oil) was examined using an exposed human hand
      bioassay. Results were compared with those of commonly used repellent N,N-diethyl
      3-methylbenzamide (DEET). In tests with six human male volunteers at a dose of
      0.5 mg/cm2, patchouli (protection time [PT], 3.67 h) was the most effective EO
      but less active than DEET (4.47 h), as judged by the PT to first bite. Very
      strong repellency also was produced by clove bud, lovage root, and clove leaf EOs
      (PT, 3.50-3.25 h), whereas strong repellency was obtained from thyme white EO
      (2.12 h). Thyme red, oregano, and geranium EOs exhibited moderate repellency (PT,
      1.24-1.11 h). At 0.25 mg/cm2, protection time of clove bud, clove leaf, and
      lovage root EOs (PT, approximately equal to 1 h) was shorter than that of DEET
      (2.17 h). An increase in the protection time was produced by binary mixtures (PT,
      2.68-2.04 h) of five EOs (clove bud, clove leaf, thyme white, patchouli, and
      savory) and tamanu oil (0.25:2.0 mg/cm2) compared with that of either the
      constituted essential oil or tamanu oil alone (PT, 0.56 h). The protection time
      of these binary mixtures was comparable with that of DEET. With the exception of
      savory EO, the other EOs, tamanu oil, and binary mixtures did not induce any
      adverse effects on the human volunteers at 0.5 mg/cm2. Thus, binary mixtures of
      essential oils and tamanu oil described merit further study as potential
      repellents for protection from humans and domestic animals from biting and
      nuisance caused by S. calcitrans.

PMID- 20695273
TI  - Gamma ray dosimetry and mating capacity studies in the laboratory on Aedes
      albopictus males.
AB  - In Italy, Aedes albopictus Skuse is currently recognized as the most dangerous
      mosquito, and as currently applied conventional control methods gave
      unsatisfactory results, we are developing alternative strategies such as the
      sterile insect technique. To find the optimal sterilizing dose, male pupae were
      exposed to different doses of gamma rays in the range 20-80 Gy, generated by a
      Cesium-137 source. The effects of male pupal age at irradiation and gamma ray
      dose on adult male emergence, sterility level, longevity, and mating capacity
      were evaluated, and dose-response curves of residual fertility were calculated.
      Radiation tests were also performed on female pupae to observe their reproductive
      capacity in case of accidental release. Results confirmed that the age at which
      the male pupa is irradiated is an important factor that affects the longevity of
      the adult, whereas the effect of age on the induced sterility level is less
      pronounced. When male pupae older than 30 h were irradiated, the longevity of the
      adults was not affected by doses up to 40 Gy. The 40-Gy dose appeared sufficient
      to induce high level of sterility (>99%) at any male pupal age for all the
      strains tested. The duration of coupling and the number of mated females per male
      appeared to be affected by the radiation received by male pupae only at doses
      higher than 40 Gy. The female pupae were more sensitive to radiation than male
      pupae, with strong reduction in fecundity and fertility at 20 Gy and complete
      suppression of oviposition at higher doses.

PMID- 20695274
TI  - Establishment of quantitative sequencing and filter contact vial bioassay for
      monitoring pyrethroid resistance in the common bed bug, Cimex lectularius.
AB  - Two point mutations (V419L and L925I) in the voltage-sensitive sodium channel
      alpha-subunit gene have been identified in deltamethrin-resistant bed bugs. A
      quantitative sequencing (QS) protocol was developed to establish a population
      based genotyping method as a molecular resistance-monitoring tool based on the
      frequency of the two mutations. The nucleotide signal ratio at each mutation site
      was generated from sequencing chromatograms and plotted against the corresponding
      resistance allele frequency. Frequency prediction equations were generated from
      the plots by linear regression, and the signal ratios were shown to highly
      correlate with resistance allele frequencies (r2 > 0.9928). As determined by QS,
      neither mutation was found in a bed bug population collected in 1993. Populations
      collected in recent years (2007-2009), however, exhibited completely or nearly
      saturating L925I mutation frequencies and highly variable frequencies of the
      V419L mutation. In addition to QS, the filter contact vial bioassay (FCVB) method
      was established and used to determine the baseline susceptibility and resistance
      of bed bugs to deltamethrin and lambda-cyhalothrin. A pyrethroid-resistant strain
      showed >9,375- and 6,990-fold resistance to deltamethrin and lambda-cyhalothrin,
      respectively. Resistance allele frequencies in different bed bug populations
      predicted by QS correlated well with the FCVB results, confirming the roles of
      the two mutations in pyrethroid resistance. Taken together, employment of QS in
      conjunction with FCVB should greatly facilitate the detection and monitoring of
      pyrethroid-resistant bed bugs in the field. The advantages of FCVB as an on-site
      resistance-monitoring tool are discussed.

PMID- 20695275
TI  - A biosecurity response to Aedes albopictus (Diptera: Culicidae) in Auckland, New
      Zealand.
AB  - A biosecurity response was triggered by the detection of Aedes albopictus (Skuse)
      (Diptera: Culicidae) at the Port of Auckland, New Zealand. Ae. albopictus does
      not occur in New Zealand and is the most significant mosquito threat to this
      country. The possibility that a founding population had established, resulted in
      a large-scale biosecurity surveillance and control program. The response was
      initiated in early March 2007 and completed by mid-May 2007. No further exotic
      mosquitoes were detected. The response surveillance program consisted of larval
      habitat surveys and high density ovi- and light trapping. It was coordinated with
      a habitat modification and S-methoprene treatment control program. The response
      policies were guided by analysis of surveillance and quality assurance data,
      population modeling, and trace-back activities. Mosquito habitat and activity
      close to port were both more abundant than expected, particularly in storm water
      drain sumps. Sumps are difficult to treat, and during the response some
      modification was required to the surveillance program and the control regime. We
      were assured of the absence or eradication of any Ae. albopictus population, as a
      result of nil detection from surveillance, backed up by four overlapping rounds
      of insecticide treatment of habitat. This work highlights the importance of port
      surveillance and may serve as a guide for responses for future urban mosquito
      incursions.

PMID- 20695276
TI  - Salivary gland thrombostasin isoforms differentially regulate blood uptake of
      horn flies fed on control- and thrombostasin-vaccinated cattle.
AB  - Thrombostasin (TS) is an anticlotting protein found in saliva of Haematobia
      irritans (horn flies). The polymorphic nature of the ts gene was first associated
      with success of horn flies blood feeding on a laboratory host, New Zealand White
      rabbits. In this study, we report results of similar studies testing blood uptake
      of horn flies feeding on a natural host, cattle. These studies confirmed the
      association of ts genotype with blood uptake of horn flies and showed that it was
      host species specific. In contrast to rabbits, blood uptake volumes of homozygous
      ts10 horn flies were lower than those of other ts genotypes when fed on control
      (ovalbumin-vaccinated) cattle. Cattle vaccinated with recombinant protein
      isoforms, rTS9 or rTB8, resisted horn fly feeding by yielding lower blood volumes
      compared with flies feeding on control cattle. The specific impact of
      vaccination, however, varied by ts genotype of flies. Cattle vaccinated with
      isoform rTS9 resisted flies of ts2, ts9, and tb8 genotype. Vaccination with
      isoform rTB8 produced resistance to ts8, ts9, and tb8 genotype flies. Horn flies
      of genotype ts10 were not affected by vaccination with either TS isoform and fed
      as well on rTS9- and rTB8-vaccinated as on control-vaccinated cattle. These
      experimental results confirm the efficacy of vaccines targeting horn fly salivary
      proteins and provide new insight into the dynamics of horn fly-cattle
      interactions in nature.

PMID- 20695277
TI  - Temporal dynamics of malaria transmission in two rural areas of Burkina Faso with
      two ecological differences.
AB  - To determine the relationship between malaria transmission intensity, clinical
      malaria, immune response, plasmodic index, and to furthermore characterize a
      malaria vaccine trial site for potential malaria vaccines candidate testing, a
      study was conducted in Tensobtenga and Balonguen, two villages in Burkina Faso
      characterized by different malaria transmission levels. The study villages are
      located in a Sudan savanna area. Malaria transmission is seasonal and peaks in
      September in these villages. Tensobtenga and Balonguen are comparables in all
      aspects, except the presence of an artificial lake and wetlands in Tensobtenga.
      The mosquitoes sampling sites were randomly selected, taking into consideration
      the number of potential breeding sites, and the number of households in each
      village. Three times a week during 12 mo mosquitoes were collected by the Center
      for Disease Control and Prevention light traps in sentinel sites. To assess the
      infectivity the mosquitoes double ELISAs tests were performed on thoraces of
      female Anopheles gambiae s.l. (Giles) and Anopheles funestus. A total of 54,392
      female Anopheles, representing 92.71% of the total mosquitoes, were collected.
      The peaks of aggressiveness because of either An. gambiae s.l. or An. funestus
      were observed in September in each of the villages. However, these peaks were
      lower in Balonguen compared with Tensobtenga. Malaria cumulative aggressiveness
      and transmission intensity because of both species peaked in September in each of
      the two villages, with lower values in Balonguen in comparison to Tensobtenga
      From February to May, malaria transmission intensity is negligible in Balonguen
      and <1 bite/person/mo is observed in Tensobtenga. These results have confirmed
      the marked seasonality of malaria transmission in the study area.

PMID- 20695278
TI  - Detection of West Nile virus RNA in mosquitoes and identification of mosquito
      blood meals collected at alligator farms in Louisiana.
AB  - Since 2001, alligator farms in the United States have sustained substantial
      economic losses because of West Nile virus (WNV) outbreaks in American alligators
      (Alligator mississippiensis). Once an initial infection is introduced into
      captive alligators, WNV can spread among animals by contaminative transmission.
      Some outbreaks have been linked to feeding on infected meat or the introduction
      of infected hatchlings, but the initial source of WNV infection has been
      uncertain in other outbreaks. We conducted a study to identify species
      composition and presence of WNV in mosquito populations associated with alligator
      farms in Louisiana. A second objective of this study was to identify the origin
      of mosquito blood meals collected at commercial alligator farms. Mosquitoes were
      collected from 2004 to 2006, using Centers for Disease Control light traps,
      gravid traps, backpack aspirators, and resting boxes. We collected a total of
      58,975 mosquitoes representing 24 species. WNV was detected in 41 pools of
      females from 11 mosquito species: Anopheles crucians, Anopheles quadrimaculatus,
      Coquillettidia perturbans, Culex coronator, Culex erraticus, Culex nigripalpus,
      Culex quinquefasciatus, Mansonia titillans, Aedes sollicitans, Psorophora
      columbiae, and Uranotaenia lowii. The blood meal origins of 213 field-collected
      mosquitoes were identified based on cytochrome B sequence identity. Alligator
      blood was detected in 21 mosquitoes representing six species of mosquitoes,
      including Cx. quinquefasciatus and Cx. nigripalpus. Our results showed that
      mosquitoes of species that are known to be competent vectors of WNV fed regularly
      on captive alligators. Therefore, mosquitoes probably are important in the role
      of transmission of WNV at alligator farms.

PMID- 20695279
TI  - Detection of Dirofilaria immitis (Nematoda: Filarioidea) by polymerase chain
      reaction in Aedes albopictus, Anopheles punctipennis, and Anopheles crucians
      (Diptera: Culicidae) from Georgia, USA.
AB  - Potential mosquito vectors of Dirofilaria immitis (Leidy) (Nematoda:
      Filarioidea), the causative agent of dog heartworm in the southeastern region of
      the United States, were collected with CDC light traps and gravid traps in seven
      counties in the state of Georgia, USA. The presence of D. immitis in these
      mosquitoes was detected by polymerase chain reaction using species-specific
      primers for the D. immitis surface or cuticular antigen. Overall, 1,574
      mosquitoes of 13 species in seven genera were collected; 92% of the specimens
      were Aedes albopictus (Skuse), Aedes vexans (Meigen), or Anopheles punctipennis
      (Say). Ae. albopictus, An. punctipennis, and Anopheles crucians Wiedemann were
      positive for D. immitis DNA. Ae. albopictus had the highest maximum likelihood
      rate of infection (2.30%; 95% confidence interval [CI] = 1.15-4.00%) followed by
      An. crucians (1.38%: 95% CI = 0.04-6.93%), and An. punctipennis (0.85%: 95% CI
      0.03-4.29%). The detection of D. immitis DNA in the heads and thoraxes of Ae.
      albopictus (0.40%; 95% CI = 0.12-2.02%) indicates that these mosquitoes can
      support the development of D. immitis to the infective stage 3 larvae.

PMID- 20695280
TI  - Detection of Francisella tularensis in Alaskan mosquitoes (Diptera: Culicidae)
      and assessment of a laboratory model for transmission.
AB  - Tularemia is a zoonotic disease caused by the Category A bioterrorism agent
      Francisella tularensis. In Scandinavia, tularemia transmission by mosquitoes has
      been widely cited in the literature. We tested >2,500 mosquitoes captured in
      Alaska and found Francisella DNA in 30% of pooled samples. To examine the
      potential for transmission of Francisella by mosquitoes, we developed a mosquito
      model of Francisella infection. Larvae of Anopheles gambiae Giles and Aedes
      aegypti (L.) readily ingest F. tularensis but do not efficiently transfer
      infective doses of the bacterium to the pupal or adult stage. After a bloodmeal
      containing Francisella, adult female An. gambiae and Ae. aegypti retained
      detectable levels of Francisella DNA for 3 d, but when they took a second
      bloodmeal, the mammalian host was not infected. This study suggests that although
      Francisella DNA can be detected in a significant portion of wild-caught
      mosquitoes, transmission of Francisella is either very inefficient or is species
      dependent for the Francisella strain or the arthropod vector.

PMID- 20695281
TI  - Sampling biases of the BG-sentinel trap with respect to physiology, age, and body
      size of adult Aedes aegypti (Diptera: Culicidae).
AB  - Currently, Aedes aegypti (L.) control strategies are being developed that involve
      manipulation of the vector at the adult stage (e.g., the use of the bacterial
      endosymbiont Wolbachia to shorten the life span of the vector population). These
      novel strategies demand adult sampling methods to measure changes in population
      size, structure (age, sex ratio), and, ultimately, the success of the program.
      Each sampling method presents certain biases. Once these biases are defined,
      methods used to estimate population size and structure can be calibrated
      accordingly, resulting in more accurate and complex estimates of the vector
      population. A series of mark-release-recapture experiments with adult Ae. aegypti
      were conducted in a large outdoor flight cage and an indoor setting in far north
      Queensland, Australia. The biases of the BG-Sentinel trap (BGS) were investigated
      across several categories, as follows: 1) mosquito age; 2) sex; 3) physiological
      status; and 4) body size. Biases were not detected across age groups or body
      sizes. A significant bias was detected across physiological groups: nulliparous
      females were recaptured at a significantly lower rate than all other groups
      except blood-fed parous females, which were also recaptured at a low rate by the
      BGS. Males were recaptured at a higher rate than all groups, but only a
      significant difference in recapture rates was observed between males and
      nulliparous females. Previous studies show that the BGS is a highly effective
      tool for Ae. aegypti surveillance. The BGS proves to be a reliable tool in Ae.
      aegypti surveillance with consistent sampling outcomes. The sampling bias of the
      BGS is measurable and can be used to generate more accurate estimates of the
      adult population and its attributes.

PMID- 20695282
TI  - Evaluation of BG-sentinel trap trapping efficacy for Aedes aegypti (Diptera:
      Culicidae) in a visually competitive environment.
AB  - The BG-Sentinel (BGS) trap uses visual and olfactory cues as well as convection
      currents to attract Aedes aegypti (L.). The impact of the visual environment on
      trapping efficacy of the BGS trap for Ae. aegypti was investigated. Four- to 5-d
      nulliparous female and male Ae. aegypti were released into a semicontrolled room
      to evaluate the effect of the presence, reflectance, and distribution of
      surrounding harborage sites on BGS trapping efficacy. Low-reflective (dark)
      harborage sites near the BGS had a negative effect on both male and nulliparous
      female recapture rates; however, a more pronounced effect was observed in males.
      The distribution (clustered versus scattered) of dark harborage sites did not
      significantly affect recapture rates in either sex. In a subsequent experiment,
      the impact of oviposition sites on the recapture rate of gravid females was
      investigated. Although gravid females went to the oviposition sites and deposited
      eggs, the efficacy of the BGS in recapturing gravid females was not compromised.
      Ae. aegypti sampling in the field will mostly occur in the urban environment,
      whereby the BGS will be among oviposition sites and dark harborage areas in the
      form of household items and outdoor clutter. In addition to understanding
      sampling biases of the BGS, estimations of the adult population size and
      structure can be further adjusted based on an understanding of the impact of dark
      harborage sites on trap captures. Outcomes from this suite of experiments provide
      us with important considerations for trap deployment and interpretation of Ae.
      aegypti samples from the BGS trap.

PMID- 20695283
TI  - Laboratory evaluation of the efficacy of fluorescent biomarkers for sugar-feeding
      sand flies (Diptera: Psychodidae).
AB  - The purpose of this study was to evaluate the use of four fluorescent dyes
      (rhodamine B, uranine O, auramine O, and erythrosin B) and two nonfluorescent
      dyes (carmoisine and indigotine) incorporated into sugar baits as biomarkers for
      phlebotomine sand flies. Each dye could be detected in sand flies fed baits with
      dye for 24 h when examined using bright field microscopy, although there was
      considerable variability in the marking produced; all sand flies that had
      ingested rhodamine B-treated sucrose solution were marked clearly. Sand flies
      that had ingested sucrose solution containing rhodamine B or uranine O at
      concentrations as low as 10 mg/L were consistently detected under fluorescence
      microscopy. None of the treatments in this study reduced the longevity of sand
      flies. All sand flies fed sucrose solution containing rhodamine B or uranine O
      were marked for at least 14 d, whereas only 20% of sand flies were marked 3 d
      after feeding on a carmoisine-treated solution. When rhodamine B and uranine O
      were combined in a single sucrose solution or when the dyes were fed sequentially
      to sand flies, both dyes could be detected in sand flies using fluorescence
      microscopy. We propose that rhodamine B- or uranine O-treated sucrose baits could
      be used in ecological studies or to identify portions of the adult sand fly
      population that could be targeted with insecticide-treated sugar baits.

PMID- 20695284
TI  - Caiman-biting mosquitoes and the natural vectors of Hepatozoon caimani in Brazil.
AB  - Mosquitoes that feed on crocodilians are poorly known, despite the potential role
      of these exothermic animals as reservoirs of arboviruses. In this article, we
      assessed the frequency, abundance, and temporal variation of caiman-biting
      mosquitoes as well as searched for the natural vectors of the blood parasite of
      caimans, Hepatozoon caimani, in the Pantanal area of central-western Brazil from
      captures conducted bimonthly from September 2006 to September 2007 and in
      February 2008. A total of 5,272 mosquitoes belonging to 10 species of five genera
      was caught on caimans. The most abundant species were Culex (Melanoconion)
      theobaldi, Mansonia (Mansonia) titillans, Mansonia (Man.) humeralis, and Mansonia
      (Man.) amazonensis, which together accounted for 80% of all sampled individuals.
      Other blood-feeding Melanoconion species were also found quite frequently on
      caimans, including Culex clarki, Culex idottus, and Culex bastagarius. Oocysts of
      H. caimani were exclusively detected in Culex species, mainly in individuals of
      the subgenus Melanoconion, and we accomplished experimental transmission from
      naturally infected mosquitoes to uninfected Caiman yacare. The highest infection
      rates were observed in Cx. theobaldi (0.55%), which is therefore indicated as the
      primary vector of H. caimani. In addition, because the above mentioned
      Melanoconion and Mansonia species are abundant, widespread, and have a broad set
      of hosts, including crocodilians, they may be suggested as potential vectors of
      arboviruses, such as West Nile virus, in the Southern Cone in South America.

PMID- 20695285
TI  - Changes in development and heat shock protein expression in two species of flies
      (Sarcophaga bullata [Diptera: Sarcophagidae] and Protophormia terraenovae
      [Diptera: Calliphoridae]) reared in different sized maggot masses.
AB  - Development of two species of necrophagous flies, Sarcophaga bullata Parker
      (Sarcophagidae) and Protophormia terraenovae (Robineau-Desvoidy) (Calliphoridae),
      was examined in different size maggot masses generated under laboratory
      conditions. Larvae from both species induced elevated mass temperatures dependent
      on the number of individuals per mass. The relationship was more evident for S.
      bullata, as larvae generated higher temperatures in every size maggot mass than
      P. terraenovae. Several development events were altered with increasing maggot
      mass size of flesh flies, and to a lesser extent blow flies, which corresponded
      with elevated temperatures. Duration of development of all feeding larval stages
      decreased with increased size of maggot mass. However, the length of development
      during puparial stages actually increased for these same flies. Puparial weights
      also declined with maggot mass size, as did the ability to eclose. The altered
      fly development was attributed to the induction of heat stress conditions, which
      was evident by the expression of heat shock proteins (23, 60, 70, and 90) in
      larval brains of both fly types.

PMID- 20695286
TI  - Breeding of Ornidia obesa (Diptera: Syrphidae: Eristalinae) on pig carcasses in
      Brazil.
AB  - Ornidia obesa F. (Diptera: Syrphidae) is usually neglected in forensic
      entomology, although adults are rather frequent on vertebrate carrion. In this
      study, conducted in southeastern Brazil in 2008, we used two pig carcasses, one
      killed by cocaine overdose and the other by shooting, to evaluate mainly the
      possible influences of the type of death on the larval development of O. obesa in
      the pig remains. We recorded the breeding of 218 adult specimens of this syrphid
      fly from the carcass killed by shooting, and none from the carcass killed by
      cocaine. These observations may open a new perspective for the use of O. obesa in
      forensic studies, considering its breeding preferences and its complete
      development on vertebrate carrion.

PMID- 20695287
TI  - Trial of a minimal-risk botanical compound to control the vector tick of Lyme
      disease.
AB  - We compared the application of IC2, a minimal-risk (25B) botanical compound
      containing 10% rosemary oil, with bifenthrin, a commonly used synthetic compound,
      and with water for the control of Ixodes scapularis Say (= Ixodes dammini
      Spielman, Clifford, Piesman & Corwin), on tick-infested grids in Maine, in an
      area where Lyme disease is established and other tick-borne diseases are
      emerging. High-pressure sprays of IC2, bifenthrin, and water were applied during
      the peak nymphal (July) and adult (October) seasons of the vector tick. No ticks
      could be dragged on the IC2 grids within 2 wk of the July spray, and few adult
      ticks were found in October or the following April. Similarly, no adult ticks
      could be dragged 1.5 wk after the October IC2 spray, and few the following April.
      No ticks were found on the bifenthrin grids after either spray through the
      following April, whereas substantial numbers of ticks remained throughout on the
      grids sprayed with water. Thus, IC2 appears to be an effective, minimum-risk
      acaricide to control the vector tick of Lyme disease.

PMID- 20695288
TI  - Formulations of deet, picaridin, and IR3535 applied to skin repel nymphs of the
      lone star tick (Acari: Ixodidae) for 12 hours.
AB  - The efficacies of a 20% 1-methyl-propyl-2- (hydroxyethyl)-1-piperidinecarboxylate
      (picaridin) spray, 20% 3-(N-acetyl-N-butyl)aminopropionic acid ethyl ester
      (IR3535) spray, 20% picaridin lotion, 10% IR3535 lotion, and 33% N,N-diethyl-3
      methylbenzamide (deet) cream in repelling nymphal lone star ticks, Amblyomma
      americanum (L.), were determined at 2-h intervals over 12 h using human subjects.
      A repellent formulation was applied in a 5-cm-wide band encircling a volunteer's
      lower leg. For each challenge, 70 host-seeking nymphs were released on each
      volunteer's ankle, and tick locations were recorded 10 min after the ticks were
      released. Ticks that crawled entirely across the repellent band were considered
      not repelled. For all formulations and time points, significantly fewer (all P <
      0.0001) A. americanum nymphs crossed the treatment bands on the volunteers'
      ankles than crossed the corresponding area on the untreated control legs.
      Formulations containing > or = 20% active ingredient were highly effective, with
      <10% of the ticks crossing through the treatment bands for any challenge during
      the 12 h. At least 40% of ticks exposed to any formulation for any challenge fell
      or crawled off the volunteers. There was no difference in effectiveness between
      the 20% spray and 20% lotion formulations of picaridin. The 10% IR3535 lotion was
      significantly less effective than the formulations with higher concentrations of
      repellent. In the formulations tested, deet, picaridin, and IR3535 provided
      lasting protection against A. americanum.

PMID- 20695289
TI  - North African and Latin American parents' and adolescents' perceptions of
      physical discipline and physical abuse: when dysnormativity begets exclusion.
AB  - This research documents the cultural norms around physical discipline and
      physical abuse among immigrant parents and youth, and assesses the impact that
      perceived divergences in these norms have on the relation between the family and
      the outer social world. Interviews were conducted with 10 parents and 10
      adolescents from North African Arab countries, and 10 parents and 10 adolescents
      from Latin America living in Canada. Results highlight that divergent discipline
      practices were perceived by participants as an important source of tension when
      they were accompanied with a demeaning image, projected by the host society onto
      the immigrant family.

PMID- 20695290
TI  - The long-term effects of the Houston Child Advocates, Inc., program on children
      and family outcomes.
AB  - The objective of the study is to investigate the longitudinal effects of the
      Houston Child Advocates, Inc., program on children's outcomes. The treatment
      group consisted of children in the court system that were assigned Child
      Advocates volunteers, and the comparison children were chosen randomly from a
      similar population of children. The treatment group had significantly higher
      scores on the protective factor and family functioning measures and received more
      social services than those in the comparison group. Children in the treatment
      group also had significantly fewer placement changes and did better academically
      and behaviorally in school than children in the comparison group.

PMID- 20695291
TI  - Child welfare professionals' experiences of childhood exposure to domestic
      violence.
AB  - This study explores the impact of childhood exposure to domestic violence and
      using family intervention techniques. In interviews, 12 child welfare
      professionals explored their experiences with the violence, the family
      interventions, the lifelong impact, and its influence on their career choice. The
      results pointed to a need for creating more opportunities for children to talk
      about their lives with professionals, for improved screening techniques, and for
      a preference for interventions focusing on rehabilitation for the batterer, which
      maintained family preservation.

PMID- 20695292
TI  - What happens when family resources are across international boundaries? An
      exploratory study on kinship placement in Mexican immigrant families.
AB  - Children in Latino immigrant families are significantly less likely to be placed
      in kinship care than other children are. Using grounded theory, the researchers
      conducted focus groups and individual interviews with child welfare workers
      working with Mexican origin families in south Texas to study the extent to which
      they use international kin placement resources. Key barriers to international
      kinship placement include lack of accurate information concerning international
      placements and conflicting agency mandates. Lack of child protective services
      policy enforcement also plays a role. Recommendations for practice and agency
      policy are discussed.

PMID- 20695293
TI  - Child welfare employee recruitment and retention: an organizational culture
      perspective.
AB  - Drawing data from an organizational culture study, this cross-sectional study
      investigates the effect of organizational culture on child welfare employee
      recruitment and retention (N=92). Findings from quantitative analyses of the
      organizational culture inventory suggest that constructive culture style in child
      welfare organizations, especially humanistic-encouraging and self-actualizing
      culture norms, highly predict recruitment through employees' perception of "fit"
      and satisfaction as a member of the organization. Limitations, future research,
      and relevant implications are discussed.

PMID- 20695294
TI  - Culturally competent systems of care with Latino children and families.
AB  - The Latino population represents the fastest growing ethnic minority in the
      United States. As a result, child welfare agencies need to be prepared to provide
      culturally appropriate services to Latino families. This paper describes an
      evaluation of a federally funded initiative designed to train child welfare
      practitioners in using an existing evidence-based framework--systems of care-
      with Latino children and families to address the need for culturally competent,
      community-based services with this population. Results indicate that trained
      participants responded positively to the systems of care framework, increased
      their knowledge of systems of care, and reported positive benefits to their
      clients through using this framework. However, challenges to implementing systems
      of care were identified. Implications of these findings and the use of systems of
      care in child welfare are presented.

PMID- 20695295
TI  - Kinship care in northern British Columbia.
AB  - An exploratory case study design using three sources of data-interviews with
      kinship caregivers, interviews with social workers, and file reviews-was used to
      identify the needs of kinship caregivers in northern British Columbia. The
      research found that kinship caregivers identified many needs that must be
      addressed if kinship caregiving is to be a viable and sustainable option for
      children in need of care.

PMID- 20695296
TI  - [Physician, society and community--a review of the development of medical
      profession in Finland].
AB  - The history of the Finnish medical profession can be considered to have begun in
      the 1830's. From the primary health care viewpoint, the history is divided into
      four periods: the era of the district doctor (1832 to 1900), the era of the
      municipal doctor (1900 to 1972), the era of the health care center doctor (from
      1972 onwards) and--as it seems--the era of the locum doctor (from the beginning
      of the 21th century onwards). In addition to education, methods and patient
      material, the physician's social status has also undergone significant changes
      with the progress from one period to another.

PMID- 20695297
TI  - [Mitochondrial recessive ataxia syndrome (MIRAS) and valproate toxicity].
AB  - The clinical phenotypes vary considerably and can be divided into three groups:
      1) childhood-onset encephalopathy and hepatopathy, 2) juvenile onset refractory
      epilepsy and migraine-like headaches, and 3) adult-onset ataxia and neuropathy
      with additional symptoms such as psychiatric symptoms and cognitive impairment.
      The life-threatening MIRAS epilepsy should be actively treated, as it is
      associated with poor prognosis. The form of MIRAS, starting as acute, treatment
      resistant epilepsy, is important to diagnose, since valproate therapy almost
      always leads to acute liver failure requiring liver transplantation.

PMID- 20695298
TI  - [Cardiovascular problems during pregnancy].
AB  - Extensive changes occur in cardiovascular haemodynamics during pregnancy. These
      adaptations are usually well tolerated by healthy women. On the other hand, for a
      pregnant woman with heart disease, these changes can sometimes be fateful. For
      doctors, it is important to understand haemodynamic changes that occur during
      pregnancy. Patients at higher risk need to be managed within a specialised
      cardiac centre. In a previously healthy woman with cardiac symptoms during
      pregnancy, a basic clinical investigation is warranted. If clinical findings
      indicate heart disease, a thorough cardiological investigation with
      echocardiography is advisable.

PMID- 20695299
TI  - [Adolescence and psychopathy].
AB  - Personality disorder refers to pervasive and inflexible behaviour causing
      problems in everyday life. Psychopathy is a personality disorder characterized by
      lack of guilt, poorly developed empathy, manipulative behaviour and callousness.
      According to most researchers, adult psychopathy has its roots in childhood
      conduct disorder, although the applicability of psychopathy in adolescents has
      been questioned. Psychopathic features have, however, raised increased interest
      in the field of adolescent psychiatry and promising findings have been published
      concerning both biological and psychosocial underpinnings of this phenomenon.

PMID- 20695300
TI  - [The Noro story--viral gastoenteritis as a problem in inpatient facilities].
AB  - Norovirus is easily transmitted from a patient, patient secretions, or spread by
      surfaces, food and drinking water infected by the virus. The symptoms are
      characterized by rapid onset, abundant vomiting or diarrhoeal disease. The
      duration of symptoms varies from half a day to five days. In hospitals the
      epidemic spreads effectively to others in the room, to other patients within the
      ward and to the staff. In suspected cases of patient infection caused by
      norovirus, new patients should not be admitted to the same room, and a separate
      WC and shower room should be reserved for the patients.

PMID- 20695301
TI  - [It is worthwhile to examine the optic disc].
AB  - Ophthalmoscopy is sometimes very difficult, especially if special ophthalmologic
      equipments are not available. However, the examination of the optic disc is a
      skill a general practitioner needs. The use of mydriatics makes it much easier.
      Examination of the optic disc head is essential when increased intracranial
      pressure is suspected. Diabetes and systemic hypertension are also diseases in
      which ophthalmoscopy is needed.

PMID- 20695302
TI  - [Amyloidosis--uncommon etiology for ascites].
AB  - Ascites is an accumulation of fluid into the peritoneal cavity. Most often it is
      an end-complication of chronic liver disease. Other reasons for ascites should be
      considered sometimes in clinical practice. We present a patient who had primary
      (AL) amyloidosis as the reason for remarkable amount of ascites. The prognosis of
      amyloidosis is poor especially if the diagnosis is delayed.

PMID- 20695303
TI  - [Update on current care guidelines: venous thrombosis and pulmonary embolism].
AB  - Approximately 50% of hospitalised patients need thromboprophylaxis. However, 30
      50% of these high-risk patients remain without adequate treatment. Treatment of
      venous thrombombolism has remained unchanged, apart from the option of
      replacement of low-molecular-weight heparin by fondaparinux in the initial
      regimen. Practical guidance is now available for unfractionated heparin.
      Administration of thrombolysis is restricted to haemostatically unstable patients
      and local massive thrombosis, where catheter-based strategies are preferred to
      systemic fibrinolytics. Although anticoagulation therapy is life-long in the case
      of patients with idiopathic thrombosis and permanent risk factors, repeated
      safety evaluations must be performed. Otherwise, the duration of anticoagulation
      treatment is individualised.

PMID- 20695304
TI  - Spending cuts start to surface.

PMID- 20695305
TI  - Oncology patients need a specialised support network.

PMID- 20695306
TI  - School nurses could be trained to identify children with problems.

PMID- 20695307
TI  - An unbalanced view.

PMID- 20695308
TI  - Challenging adverse reactions in children with food allergies.
AB  - The Department of Health (2006) has highlighted that food allergy is increasing
      in prevalence. In response, Tameside General Hospital in Greater Manchester has
      developed a dedicated children's allergy service. By using skin tests, followed
      by oral consumption of a particular food, the clinic is able to establish
      allergies and prevent future adverse reactions. This article summarises the
      findings of an audit of food challenges that were undertaken at the clinic.

PMID- 20695309
TI  - Supportive holding or restraint: terminology and practice.
AB  - The meaning of supportive holding versus restraint in children's nursing has been
      debated for some time. Supportive holding has been defined as a hold that
      supports the child through a therapeutic intervention, and restraint as a hold
      that overpowers the child who may be a danger to themselves or others. Both are
      conducted in the philosophy of best interest. The Royal College of Nursing (2010)
      guidance suggests adopting the terms therapeutic holding and restrictive physical
      intervention. This article was accepted before the new guidance was published.
      However, with authors still using terms interchangeably, it is important to
      debate whether there is a clear demarcation in terminology and practice, or
      whether one is a continuation of the other, differentiated by the degree of force
      used.

PMID- 20695310
TI  - A need for play specialists in Japanese children's wards.
AB  - The importance of distraction techniques and play therapy for sick children has
      long been recognised by nurses in the UK and other western countries. Although
      these techniques are not so well established in Japan there is growing interest
      in them. The authors conducted a survey and found that children's nurses in Japan
      appreciated the value of distraction techniques and play therapy. They argue that
      attitudes to using them on children's wards in Japan are changing, but there is
      still a lack of training and few play specialists.

PMID- 20695311
TI  - Stark contrasts in hospital care.
AB  - As a third-year nursing student Sofia Razaq spent a four-week elective working in
      a children's ward in Morocco. In this article she describes the main differences
      between working there and in the U.K.

PMID- 20695312
TI  - Never too young to learn.

PMID- 20695313
TI  - Team players.

PMID- 20695314
TI  - Think on your feet.

PMID- 20695315
TI  - Overcoming challenges.

PMID- 20695316
TI  - Congress, pay thy physicians.

PMID- 20695317
TI  - Health care reform still forming.

PMID- 20695318
TI  - The renal diet in 2010: is it time for a shake up?
AB  - Food manufacturers add phosphate salts to their products to act as a preservative
      to extend shelf life. However, this added phosphorus poses a problem for dialysis
      patients and their caregivers because it is difficult to quantify the amount of
      phosphorus in a patient's diet. This article discusses the difference between
      organic and inorganic phosphorus, how the added phosphorus affects previously
      safe food choices, and the need to update renal diet information so hemodialysis
      patients can more effectively track their intake.

PMID- 20695319
TI  - The changing tide in ESRD care.

PMID- 20695320
TI  - Preparing for the bundle: one year later.

PMID- 20695321
TI  - The ESRD bundle creates a perfect storm.

PMID- 20695322
TI  - Will the new ESRD payment bundle signal the end of rural hospital-based dialysis
      clinics?

PMID- 20695323
TI  - Preparing for the bundle. Small and independent providers brace for the impact.

PMID- 20695324
TI  - Provider rankings see minor adjustments, ready for bundle's arrival.

PMID- 20695325
TI  - Renal Advantage looks toward home as part of its growth strategy.

PMID- 20695326
TI  - Careful with that axe.

PMID- 20695327
TI  - On a mission to be the advocates of excellence.

PMID- 20695328
TI  - Infectious enthusiasm. Interview by Sue Learner.
AB  - A nurse specaist's dedication and achievements in infection control have earned
      her a national award.

PMID- 20695329
TI  - The power of purchase.
AB  - The fourth of six articles on challenges to nursing explores the importance of
      service commissioning.

PMID- 20695330
TI  - Future questions.
AB  - The charity C3 Collaborating for health wants nurses' views on how health care
      and nursing roles might evolve.

PMID- 20695331
TI  - The allergen that is all around us.

PMID- 20695332
TI  - Aliens among us.

PMID- 20695333
TI  - Deaf patient showed me value of two-way communication.

PMID- 20695334
TI  - Management of long-term conditions in a prison setting.
AB  - This article, the fourth in a five-part series, explores the management of long
      term conditions in the prison population, as well as patient-centred approaches
      to care and the challenges this may present. It discusses the effective
      management of chronic diseases and the importance of evidence-based practice in
      improving offender health care. The need for an understanding of the sociological
      and psychological perspectives of living with a long-term condition is explained.

PMID- 20695335
TI  - Best practice in the measurement of body temperature.
AB  - In the last two decades, there has been a significant change in the technology of
      clinical thermometry. Mercury-in-glass thermometers have been replaced with
      electronic devices that offer faster readings with minimal inconvenience to the
      patient. Each user should be aware of the characteristics and limitations of
      these devices to interpret correctly the temperature reading on the display. The
      article provides an insight into commonly used clinical thermometers, how they
      determine each temperature reading and, crucially, how users affect the
      measurement process.

PMID- 20695336
TI  - Prevention of unintentional injury in the community setting.
AB  - This article focuses on the types of unintentional injuries that may occur in the
      community and individuals who are most vulnerable. It discusses the nurse's role
      in the prevention of injuries through the assessment of risk and health promotion
      strategies.

PMID- 20695337
TI  - Acute stroke.

PMID- 20695338
TI  - Speak my language.

PMID- 20695339
TI  - In the media spotlight.

PMID- 20695340
TI  - A workplace menace.

PMID- 20695341
TI  - [Peter Simon Pallas (1741-1811). The structure of the organic world and the
      notion of species. On the bicentenary of the death of P. S. Pallas].
AB  - An attempt has been made in the current paper to dispel two myths concerning
      Peter Simon Pallas, myths which have led historians of biology to distort the
      picture of some of the general biological ideas developed by that eminent
      naturalist of the Age of Enlightenment. The first point dealt with in the paper
      involves the myth that Pallas had allegedly drafted a 'tree of life' diagram, one
      of the many graphic representations of this kind to appear in later times,
      illustrating the structure of the organic world. The tree, of which Pallas merely
      left a short description (but not a depiction), took--in the articles of authors
      who wrote about it--a variety of graphic forms (largely dependent on the authors'
      pictorial inventiveness), with all the authors assuring the readers that they
      illustrated their reasoning with the help of Pallas's tree of life, but never
      mentioning that it was they themseIves who had drawn it. The current paper
      presents a juxtaposition of a number of such diagrams, drawn by different
      authors: the great diversity of the diagrams is sufficient proof that the
      existence of one, original 'Pallas tree' is just a myth. Another aspect of the
      myth has to do with the view that the tree supposedly illustrated phylogenetic
      dependencies - in fact, Pallas described affinity relationships between groups in
      the animal world. The present paper investigates how the 'tree of life' myth has
      developed, and reveals the mechanism that has most likely led to the myth being
      perpetuated in writings on the history of biology. The second issue discussed in
      the current paper relates to the myth of how Pallas's general views on biology
      allegedly evolved. The naturalist was supposed to have moved from transformism
      (characteristic of early stages of his work) to the idea of the immutability of
      species, formed in the period of his full scientific maturity. The current paper
      proves, inter alia on the basis of little known and not easily accessible
      writings by the scholar, that Pallas espoused the Age of Enlightenment's deism,
      an important element of which was the idea of the immutability of species, to
      which Pallas steadfastly subscribed. On the other hand, the analysis presented in
      the paper has revealed that Pallas seemed to consider the problem of species on
      two planes: that of free-roaming wild species, which remained absolutely
      immutable, and that of domesticated species, which did manifest some mutability,
      largely sustained by human effort but never transgressing species boundaries. It
      was also--and only--under domestication that monsters appeared. Pallas did
      contemplate, not without much hesitation, teratogenesis as a possible mechanism
      behind speciation, but--given the lethal character of monstrous modifications--he
      did not treat it as the real mechanism of speciation.

PMID- 20695343
TI  - Join us to show your commitment to the eight high impact actions.

PMID- 20695344
TI  - Exploring the principles of best practice discharge to ensure patient
      involvement.
AB  - Recent guidance features 10 practical steps to improve the process of patient
      discharge and transfer- one of the eight high impact actions for nursing and
      midwifery. This article examines the current policy context surrounding discharge
      in the health service, and gives practical advice on implementing the 10 steps.
      For each step the Lean methodology has been used. According to the NHS Institute
      for Innovation and Improvement, Lean is an improvement approach to improve flow
      and eliminate waste, developed by Toyota. The principles discussed in this
      article should help hospital trusts to apply a systematic approach to the
      discharge planning process and prevent readmissions while improving the quality
      of patient discharge.

PMID- 20695345
TI  - Why do patients with complex palliative care needs experience delayed hospital
      discharge?
AB  - Patients with complex palliative care needs often experience delays in being
      discharged from hospital. A clinical audit examined the reasons for this by
      examining the case notes of 40 patients. Recommendations were made and
      implemented, and a repeat audit will assess their effectiveness.

PMID- 20695346
TI  - Using an accreditation scheme to demonstrate quality in mental healthcare
      settings.
AB  - A new accreditation programme for psychiatric intensive care units aims to
      improve the quality of services. This article examines the programme's content,
      the process of accreditation and why such schemes are important.

PMID- 20695347
TI  - Dementia care. 2: Exploring how nursing staff manage challenging behaviour.
AB  - BACKGROUND: This second in a three part series on dementia care explores
      different approaches to care; part 1 examined communication issues. Dementia care
      traditionally uses a medical approach to management, which focuses on the
      standard neurogenic disease paradigm, but now many care home staff and health
      professionals are moving towards a person centred approach, based on
      biopsychosocial explanations. AIM: This study sought to examine the extent to
      which care home staff have adopted a person centred approach. METHOD: Focus
      groups were carried out with 36 direct care staff from nine care homes. RESULTS:
      The study found evidence that both models of dementia care were in use. Three
      homes mainly used the medical approach, four the person centred approach and two
      were moving towards the latter. CONCLUSION: Training in biopsychosocial
      approaches to managing challenging behaviours in dementia is needed for care home
      staff, family and other health professionals.

PMID- 20695348
TI  - NHS Evidence helps you to provide cost effective care.

PMID- 20695350
TI  - New government, fresh focus.

PMID- 20695351
TI  - Nurse prescribing and community practitioners.
AB  - More than 30,000 nurses across the United Kingdom are qualified to prescribe from
      the Nurse Prescribers' Formulary for Community Practitioners. Approximately
      14,000 nurses have become qualified to prescribe as both independent and
      supplementary prescribers. The numbers of community nurses undertaking
      independent/supplementary prescribing training and extending their prescribing
      skills has increased. Prerequisites for nurses wishing to undertake
      independent/supplementary prescribing training include the ability to study at
      level3 (degree level), at least three years' experience as a qualified nurse,
      agreement from a doctor that they will contribute to the 12/13 days' learning in
      practice, and occupying a post in which they would be expected to prescribe. The
      39-day training programme leading to the dual qualification of
      independent/supplementary prescriber generally runs over 3-6 months, but must be
      completed within one year. Although the initial implementation of nurse
      prescribing was slow, changes surrounding prescribing policy have been rapid over
      recent years. Prescribing is now an extended role for many thousands of nurses,
      and independent supplementary prescribers have virtually the same prescribing
      rights as doctors. The many benefits of prescribing as predicted by the
      Government have been achieved and additional benefits have been reported. A
      number of benefits have been reported by nurses who prescribe from the Community
      Practitioners' Formulary. These benefits include time savings and convenience, a
      belief that patients receive better information from nurses about prescriptions,
      as well as an increased sense of satisfaction, status and autonomy. However, it
      is apparent that many of these nurses are not utilising their prescribing skills
      and this needs further exploration.

PMID- 20695352
TI  - Understanding emotional abuse.
AB  - Research shows that many practitioners do not feel they have adequate knowledge
      to understand and respond to cases of emotional abuse. Emotional abuse is present
      in all types of child abuse but can exist in its own right without other forms of
      abuse. It can be difficult to identify because there may be no signs of physical
      injury and there is usually no disclosure from the child. This article provides a
      guide, including definitions, prevalence statistics and key research findings.

PMID- 20695353
TI  - Current issues in midwifery.

PMID- 20695354
TI  - Postnatal pelvic floor dysfunction: conservative treatment and management
      options.
AB  - Thirty per cent of postnatal women will suffer with one or more symptoms of
      pelvic floor dysfunction. Left untreated, symptoms can lead to social isolation
      and embarrassment. Long-term co-morbidity is increased in women who have symptoms
      of pelvic floor dysfunction postnatally, therefore assessing and treating these
      symptoms when they develop is crucia for the wellbeing of women. This article
      describes the key issues in the identification, assessment and conservative
      management of women with pelvic floor dysfunction in the postnatal period.

PMID- 20695355
TI  - Empowering parents to understand and manage children's behaviour.
AB  - While there are many projects successfully targeting the problems associated with
      the management of unwanted behaviour in children, this article suggests that all
      parents would benefit from a greater understanding of how to manage such
      behaviour. Health visitors and their teams are well placed to help parents to
      understand what is normal behaviour for different ages and developmental stages
      and empower them to find solutions for unwanted behaviours. However, current
      financial constraints which allow health visitors to focus only on specific
      groups mean that they are not able to provide this help as a universal service.
      Teaching parents to observe their child and record their findings, an approach
      used by a health visitor-led programme in Wales, provides an opportunity for
      significant learning to take place. Through such programmes, parents acquire
      skills that boost their self-esteem and confidence, which in turn empower them to
      be proactive in the promotion of their family's health and well-being.

PMID- 20695356
TI  - Encouraging and supporting women through breast-feeding.
AB  - The Department of Health and the World Health Organization recommend that mothers
      should exclusively breast-feed their infants for the first six months of their
      lives. Very few mothers in the UK achieve this, but with good support and
      encouragement from health professionals this could be attained. Health
      professionals, however, need to have knowledge of the process of breastfeeding
      and be able to adopt a problem-solving approach to the difficulties mothers
      encounter, in order to give appropriate evidence-based care.

PMID- 20695357
TI  - Preventing cancer: the role of food, nutrition and physical activity.
AB  - The recommendations of a major report on dietary aspects of cancer prevention are
      summarised and discussed. The findings of The World Cancer Research Fund
      (WCRF)/American Institute for Cancer Research (AICR) Second Expert Report Food,
      Nutrition, Physical Activity, and the Prevention of Cancer: a Global Perspective
      were published in 2007 and remain valid. The Report reviewed the relationship
      between food, nutrition, physical activity, body fatness and 17 cancer sites. The
      goal of the Report was to review all the relevant research, using precise and
      reproducible methodologies. An expert panel reviewed the evidence. Based upon
      evidence that was graded "convincing" or "probable", a series of 10
      recommendations to reduce the risk of developing cancer was produced. One of the
      most important factors is maintaining a healthy weight throughout life, which can
      be achieved by regular physical activity and limiting consumption of energy-dense
      foods and sugary drinks. Other important dietary measures include consuming a
      diet high in plant-based foods, limiting intakes of red meat, and avoiding salty
      foods and processed meat. Alcohol should be consumed in modest amounts, if at
      all. Dietary supplements are not recommended for cancer prevention.

PMID- 20695358
TI  - Food allergies in children: the difference between cow's milk protein allergy and
      food intolerance.

PMID- 20695359
TI  - [Demographic, clinical and polysomnographic differences between men and women].
AB  - Obstructive sleep apnea (OSA) is still an undiagnosed disease in women, possibly
      due to differences in clinical presentation or a higher tolerance to symptoms.
      There are no studies to assess these differences in Romanian population. AIM: we
      conducted this study to assess these differences (demographics, clinical
      presentation, and polysomnographic findings) between men and women. MATERIAL AND
      METHODS: Our study group comprised 131 patients (57 women) diagnosed with OSA in
      the sleep lab from Clinic of Pulmonary Diseases, Iasi, Romania. We analyzed
      polysomnographic recordings, demographic data and all the information gathered in
      their personal files from sleep lab. RESULTS: Women were significantly older than
      men (59.3 +/- 12.6 vs, 46.7 +/- 22.8), and their body mass index was also
      significantly higher (39.6 +/- 5.7 vs, 31.2 +/- 7.9). Women declared more
      frequent insomnia, morning headaches and excessive daytime sleepiness. Men accuse
      more frequent snoring and witnessed apneas. Apnea-hypopnea index (AHI) was
      statistically higher in men compared to women (64.0 +/- 25.7 vs, 45 +/- 21.9, p <
      0.001), and also the snoring percentage (35.7 +/- 23.9 vs. 16.8 +/- 2.5, P <
      0.001); women had a higher sleep onset latency (26.8 +/- 36.5 vs. 20.6 +/- 25.4,
      P < 0.03), the arousal index was significantly higher in women than in men (AI:
      42.7 +/- 34.5 vs. 25.4 +/- 15.6, P < 0.04), and also an increased total sleep
      time was observed in women compared to men. There were no significant differences
      between time bellow 90% saturation in men vs. women. CONCLUSION: women with OSA
      are presenting with complaints that send us to other disorders than sleep apnea
      (depressive moods, insomnia, morning headaches) and the polysomnographic features
      that characterize sleep quality are more affected in women. Clinicians need to be
      aware of these differences when assessing women for the possibility of OSA in
      order to allow a correct management of the disease.

PMID- 20695360
TI  - [Lung metastases secondary to bronchopulmonary cancer].
AB  - OBJECTIVES: The goal of this study is to establish the surgical options in the
      management of patients with lung metastases secondary to lung cancer. MATERIAL
      AND METHOD: A retrospective study was performed on 34 patients admitted in our
      hospital between January 2000 and June 2009. RESULTS: Most of the patients were
      males over 45 years old. There are 2 groups: one (the most numerous) represents
      the patients in whom the metastases were discovered concomitantly with the
      symptomatic primary lung tumor and the other group consists in patients who
      previously underwent surgery and in whom the metastases were detected at
      imagistic postoperative follow-ups after a variable disease-free interval of time
      ranging from 5 months to 11 years. The therapeutic option most commonly used in
      the first-group patients was pneumonectomy and wedge resection in the second
      group. Post-operative evolution was favourable in 88% of the cases. CONCLUSIONS:
      The surgical treatment of lung metastases secondary to lung cancer is a valuable
      therapeutic option. When surgical treatment is indicated the most frequently used
      technique is wedge resection followed by pneumonectomy. The postoperative imaging
      follow-ups play an important role in the early detection of lung metastases
      developing after the surgical management of the primary lung tumour.

PMID- 20695361
TI  - [Inhaled corticosteroids in COPD and the risk of pneumonia].
AB  - Concern is continuing about increased risk of pneumonia in patients with chronic
      obstructive pulmonary disease (COPD) who use inhaled corticosteroids. The aim of
      this work is to present a few results from the literature about this problem.

PMID- 20695362
TI  - [Peanut allergy].
AB  - Peanut allergy currently affects around 1% of the UK and US paediatric population
      and represents a major healthcare concern because it is outgrown in less than 20%
      of cases and is a major cause of anaphylaxis. Its main symptoms, triggered by
      peanut ingestion, are cutaneous (urticaria, erythema, angioedema),
      gastrointestinal (abdominal pain, vomiting, diarrhoea), respiratory (wheezing,
      dyspnoea) and cardiovascular (hypotension, arrhythmia, shock). The usual onset of
      symptoms occurs soon after peanut ingestion (minutes to hours); however some
      patients have biphasic reactions, with exacerbations occurring up to 8 hours
      later. Peanut allergy diagnostic is based mainly upon the medical history
      (preferably including a diet diary and elimination diets), skin testing, peanut
      specific IgE measurement and ideally a peanut oral challenge. Peanut allergy
      management includes monitorisation and education for avoiding peanut-containing
      foods and for recognising and treating anaphylactic episodes (self-injectable
      adrenalin and rapid-acting antihistamines). In the past, anti-IgE antibodies were
      shown to decrease the risk of anaphylaxis by reducing the allergic patients'
      reactivity to peanuts. Recent investigations, driven by the need to develop
      efficient treatment and prevention strategies for peanut allergy, suggest that
      oral immunotherapy with peanuts, although exposing the patients to significant
      risk, may represent a promising therapeutic approach. Furthermore, contrary to
      the general view that peanut avoidance in infants could prevent peanut allergy, a
      recent study shows that the opposite may be true as early consumption of peanuts
      in infancy is associated with a low prevalence of peanut allergy.

PMID- 20695363
TI  - Multiple bilateral traumatic pulmonary pseuodocysts in a 53 year-old male
      diagnosed retrospectively.
AB  - Traumatic pulmonary pseudocyst (TPPC) is a rare complication, which might be
      encountered after thoracic trauma. It is most often (75-100%) seen in children
      and young adults. A 53 year-old male presented with multiple bilateral pulmonary
      cysts after a motor vehicle accident. We evaluated the patient for abscess,
      tuberculosis, and Wegener's granulomatosis with negative results. Follow up chest
      X-rays showed spontaneous resolutions of pseudocysts with replacement with
      pneumatocelae. In patients with recent chest trauma, TPPC should be kept in mind
      to prevent unnecessary invasive tests.

PMID- 20695364
TI  - [Mycobacterial mediastinal adenopathy].
AB  - Tuberculosis is a frequent cause of prolonged fever. Mediastinal lymph node
      enlargement is an uncommon feature of intrathoracic tuberculosis in adults. The
      authors present the case of a 64 year old man who developed prolonged fever and
      was admitted to Clinical Hospital of Infectious Diseases and Pneumophtisiology
      Dr. Victor Babes Timisoara during 06.04-15.04.2009. Diagnosis of mediastinal
      lymph node tuberculosis was established only after axillary thoracotomy and
      biopsy of tumoral mass, although the first results obtained after mediastinoscopy
      were negative. Dynamics of biological features, diagnostic pitfalls, differential
      diagnosis difficulties and peculiar aspects of evolution are presented.
      Mediastinal tuberculous adenopathy, without associated pulmonary involvement is a
      rare form of presentation among adults, generally evolving with sustained fever.
      Diagnosis of mediastinal tuberculosis is difficult due to non-specific clinical
      aspects and lack of characteristic radiographic features and so invasive
      diagnostic procedures gain importance (mediastinoscopy and biopsy).

PMID- 20695365
TI  - [Remediastinoscopy--current indications. A case report].
AB  - Current indications for remediastinoscopy include an inadequate first procedure,
      recurrent and second primary lung cancer, lung cancer occurring after an
      unrelated disease such as lymphoma, and restaging after induction therapy.
      Nowadays, restaging is the most frequent indication for remediastinoscopy. We
      present the case of a 42 years old male with a mediastinoscopy performed in
      another surgical unit 4 months before being admitted in our department. The CT
      scan showed bulky mediastinal lymph node enlargement, in evolution compared with
      the prior one, and no other lesions in the lung parenchyma. As the
      histopathological examination from the first specimen was negative, a diagnosis
      was requested in order to allow a correct treatment. A remediastinoscopy was
      successfully performed and avoided a more invasive procedure.

PMID- 20695366
TI  - [Bronchiolitis and pulmonary hypertension].
AB  - OBJECTIVES: The study was undertaken to assess whether previously healthy infants
      with bronchiolitis develop elevated pulmonary artery pressures. MATERIAL AND
      METHODS: We performed 2D and Doppler echocardiography in 94 infants, aged between
      2 and 12 months, from November 2007 to December 2009. 47 infants had
      bronchiolitis and 47 were in the control group. We excluded children with
      congenital heart diseases and other conditions associated with pulmonary
      hypertension. The method of time to peak velocity corrected for heart rate was
      used to estimate pulmonary arterial pressure (PAP). A Student's t-test for
      independent samples was used to compare the mean values of variables. OUTCOMES:
      Increased mean pulmonary pressures (> 25 mmHg) were measured in 13 infants with
      bronchiolitis. The values were categorized as mild-moderate pulmonary
      hypertension. Mean PAP were significantly increased in subjects with
      bronchiolitis, vs. control (p = 0.001). In infants with bronchiolitis,
      hospitalisation was significantly longer at patients with pulmonary hypertension
      vs. normal PAP (p = 0.006). Mean PAP were significantly increased in subjects
      with a moderate/severe episode of wheezing at admission vs. a mild episode (p =
      0.001). CONCLUSION: Echocardiography brings valuable informations regarding
      pulmonary hypertension in bronchiolitis. PHT could be a criterion in establishing
      the severity of disease, a prognosis factor and an element of therapeutic
      guidance.

PMID- 20695367
TI  - [Esophageal pathology with respiratory impact].
AB  - We present some of digestive diseases: achalazia, esophageal diverticula and
      esophageal fistula, which in their evolution determine respiratory symptoms:
      dispnea, cough and imitate until confusion respiratory diseases. The diagnosis is
      most of the time difficult and it needs special investigations. A better
      knowledge of these diseases helps us to avoid mistakes in diagnosis.

PMID- 20695368
TI  - [Anticholinergics and their cardiovascular effects--between fear and reality].

PMID- 20695369
TI  - [New progress of related research of bone tissue engineering].
AB  - OBJECTIVE: To review new progress of related research of bone tissue engineering
      in recent years. METHODS: Domestic and international literature concerning bone
      tissue engineering was reviewed and analyzed. RESULTS: In the recent years, great
      progression had been made in the research and development of bone tissue
      engineering, it had been used in more and more hospitals, and relevant national
      regulations and protocols had been set up. As to seed cells of bone tissue
      engineering, autologous and allogeneic stem cells had been widely used, while
      recently embryonic stem cells and induced pluri potent stem cells had attracted
      most attentions. In the field of scaffolds materials, significant improvements
      had been made, from natural extractions to artificial polymers; from single
      construction to multiple compounds with surface modifications. As to the methods
      of construction, the static seeding approach had been widely accepted, and the
      applications of bioreactor had provided a stable and various micro-environment
      for the vitro-culture of different stem cells, which had been regarded as an
      alternative way of vitro-culture and construction for bone tissue engineering.
      CONCLUSION: With the tremendous help of the techniques and approaches above, we
      shall expect a promising future of a new generation bone tissue engineering based
      medical products in the years to come.

PMID- 20695370
TI  - [Combined application of green fluorescent protein labeling and confocal laser
      scanning microscope three-dimensional reconstruction to monitor construction and
      in vivo transplantation of tissue engineered bone].
AB  - OBJECTIVE: The combined application of green fluorescent protein (GFP) and
      confocal laser scanning microscope three-dimensional reconstruction (CLSM-3DR)
      were used to monitor the construction and in vivo transplantation of tissue
      engineered bone (TEB), to provide for technology in selection of scaffolds and
      three-dimensional constructional methods. METHODS: After bone marrow mesenchymal
      stem cells (BMSCs) were isolated from a 2-year-old green goat by a combination
      method of density gradient centrifugation and adherent culture, and the
      expressions of CD29, CD60L, CD45, and CD44 in BMSCs were detected by flow
      cytometry. Plasmid of pLEGFP-N1 was amplified, digested by enzymes (Hind III,
      BamH I, Sal I, and Bgl II), and identified. Transfection of pLEGFP-N1 into PT67
      cells was performed under the help of liposome. Positive PT67 cells were picked
      out with G418, and proliferated for harvesting virus. Based on the titre of
      virus, after BMSCs were infected by virus containing pLEGFP-N1, GFP positive
      BMSCs were collected and proliferated for seeding cells. TEB was fabricated by
      GFP positive BMSCs and decalcified bone matrix (DBM) and observed by CLSM-3DR for
      the evaluation of the distribution and proliferation of seeding cells. After TEB
      was transplanted in the defect of goat femur, CLSM was used for observing the
      survival and distribution of GFP positive cells in the grafts. RESULTS: The
      isolated cells were fibroblast-like amorphous, with the positive expression of
      CD29 and CD44, and negative expression of CD60L and CD45. The digested production
      of pLEGFP-N1 was collected for ionophoresis, whose results showed the correct
      fragment length (6 900 bp). The virus of pLEGFP-N 1 was harvested by transfection
      of pLEGFP-N1 into PT67 cells and used for further infection to obtain GFP
      positive BMSCs. The proliferated GFP positive BMSCs and DBM were used for
      fabrication of TEB. The distribution, proliferation, and migration of BMSCs in
      TEB were observed by CLSM-3DR. GFP positive cells also were observed in images of
      TEB graft in goat femur 28 days after transplantation. CONCLUSION: The BMSCs
      labeled by GFP in three-dimensional scaffold in vivo were monitored well by CLSM
      3DR. It suggests a wide use potency in monitoring of three-dimensional cultured
      TEB.

PMID- 20695371
TI  - [Experimental comparative study on osteogenic activity between freeze-dried
      tissue engineered bone and tissue engineered bone].
AB  - OBJECTIVE: Tissue engineered bone (TEB) lacks of an effective and feasible method
      of storage and transportation. To evaluate the activity of osteogenesis and
      capability of ectopic osteogenesis for TEB after freeze-dried treatment in vitro
      and in vivo and to explore a new method of preserving and transporting TEB.
      METHODS: Human bone marrow mesenchymal stem cells (hBMSCs) and decalcified bone
      matrix (DBM) were harvested from bone marrow and bone tissue of the healthy
      donators. TEB was fabricated with the 3rd passage hBMSCs and DBM, and they were
      frozen and dried at extremely low temperatures after 3, 5, 7, 9, 12, and 15 days
      of culture in vitro to obtain freeze-dried tissue engineered bone (FTEB). TEB and
      FTEB were observed by gross view and scanning electron microscope (SEM). Western
      blot was used to detect the changes of relative osteogenic cytokines, including
      bone morphogenetic protein 2 (BMP-2), transforming growth factor beta1 (TGF
      beta1), and insulin-like growth factor 1 (IGF-1) between TEB and FTEB. The
      ectopic osteogenesis was evaluated by the methods of X-ray, CT score, and HE
      staining after TEB and FTEB were transplanted into hypodermis space in athymic
      mouse. RESULTS: SEM showed that the cells had normal shape in TEB, and secretion
      of extracellular matrix increased with culture time; in FTEB, seeding cells were
      killed by the freeze-dried process, and considerable extracellular matrix were
      formed in the pore of DBM scaffold. The osteogenic cytokines (BMP-2, TGF-beta1,
      and IGF-1) in TEB were not decreased after freeze-dried procedure, showing no
      significant difference between TEB and FTEB (P > 0.05) except TGF-beta1 15 days
      after culture (P < 0.05). The ectopic osteogenesis was observed in TEB and FTEB
      groups 8 and 12 weeks after transplantation, there was no significant difference
      in the calcified level of grafts between TEB and FTEB groups by the analysis of X
      ray and CT score. On the contrary, there was no ectopic osteogenesis in group DBM
      12 weeks after operation. HE staining showed that DBM scaffold degraded and
      disappeared 12 weeks after operation. CONCLUSION: The osteogenic activity of TEB
      and FTEB is similar, which provides a new strategy to preserve and transport TEB.

PMID- 20695372
TI  - [Effect of tissue engineered bone implantation with vascular bundle and sensory
      nerve bundle on expression of neurokinin 1 receptor and vasoactive intestinal
      peptide type 1 receptor in vivo].
AB  - OBJECTIVE: Vascular bundle and sensory nerve bundle implantation can promote the
      osteogenesis of tissue engineered bone. To investigate whether vascular bundle
      and sensory nerve bundle implantation will affect the expressions of neurokinin 1
      receptor (NK1R) and vasoactive intestinal peptide type 1 receptor (VIPR1).
      METHODS: Fifty-four 5-month-old New Zealand rabbits were selected. Autologous
      bone marrow was aspirated from the posterior iliac spine of rabbits, and the bone
      marrow mesenchymal stem cells (BMSCs) were proliferated in vitro. At the 3rd
      passage, the BMSCs were cultured in the osteogenic culture medium for 7 days. The
      tissue engineered bone was prepared by the combined culture of these osteoblastic
      induced BMSCs and beta tricalcium phosphate scaffold material. A 1.5 cm segmental
      bone defect was created at the right femur of rabbits. After the plate fixation,
      defects were repaired with sensory nerve bundle plus tissue engineered bone
      (group A, n = 18), with vascular bundle plus tissue engineered bone (group B, n =
      18), and tissue engineered bone only (group C, n = 18). X-ray examination was
      used to evaluate the degree of the ossification. The expression levels of NK1R
      and VIPR1 were measured by the immunohistochemistry analysis and the mRNA
      expression of NK1R and VIPR1 by real-time PCR at 4, 8, and 12 weeks after
      operation. RESULTS: The better osteogenesis could be observed in group A and
      group B than in group C at all time points. X-ray scores were significantly
      higher in group B than in groups A and C (P < 0.05) at 4 weeks, and in groups A
      and B than in group C (P < 0.05) at 8 and 12 weeks. The mRNA expressions of NK1R
      and VIPR1 were highest at 8 weeks in groups A and B and gradually decreased at 12
      weeks (P < 0.05); the expressions were higher in groups A and B than that in
      group C (P < 0.05), and in group B than group A (P < 0.05). Immunohistochemistry
      analysis showed that the expressions of NK1R and VIPR1 were highest at 8 weeks in
      3 groups, and the expressions were higher in groups A and B than in group C.
      CONCLUSION: Implanting vascular bundles into the tissue engineered bone can
      significantly improve the expression levels of NK1R and VIPR1. It is an ideal
      method to reconstruct composite tissue engineered bone.

PMID- 20695373
TI  - [Osteogenic activity of porous calcium phosphate ceramics fabricated by rapid
      prototyping].
AB  - OBJECTIVE: Calcium phosphate bioceramics has a broad application prospect because
      of good biocompatibility, but porous scaffolds with complex shape can not be
      prepared by the traditional methods. To fabricate porous calcium phosphate
      ceramics by rapid prototyping and to investigate the in vitro osteogenic
      activities. METHODS: The porous calcium phosphate ceramics was fabricated by
      rapid prototyping. The bone marrow mesenchymal stem cells (BMSCs) were isolated
      from bone marrow of Beagle canine, and the 3rd passage BMSCs were seeded onto the
      porous ceramics. The cell/ceramics composite cultured in osteogenic medium were
      taken as the experimental group (group A) and the cell/ceramics composite
      cultured in growth medium were taken as the control group (group B). Meanwhile,
      the cells seeded on the culture plate were cultured in osteogenic medium or
      growth medium respectively as positive control (group C) or negative control
      (group D). After 1, 3, and 7 days of culture, the cell proliferation and
      osteogenic differentiation on the porous ceramics were evaluated by DNA
      quantitative analysis, histochemical staining and alkaline phosphatase (ALP)
      activity. After DiO fluorescent dye, the cell adhesion, growth, and proliferation
      on the porous ceramics were also observed by confocal laser scanning microscope
      (CLSM). RESULTS: DNA quantitative analysis results showed that the number of
      BMSCs in all groups increased continuously with time. Plateau phase was not
      obvious in groups A and B, but it was clearly observed in groups C and D. The
      CLSM observation indicated that the activity of BMSCs was good and the cells
      spread extensively, showing good adhesion and proliferation on the porous calcium
      phosphate ceramics prepared by rapid prototyping. ALP quantitative analysis
      results showed that the stain of cells on the ceramics became deeper and deeper
      with time in groups A and B, the staining degree in group A were stronger than
      that in group B. There was no significant difference in the change of the ALP
      activity among 4 groups at the first 3 days (P > 0.05); the ALP activity
      increased obviously in 4 groups at 7 days, group A was significantly higher than
      other groups (P < 0.05) and groups C, D were significantly higher than group D (P
      < 0.05). CONCLUSION: The porous calcium phosphate ceramics has good
      cytocompatibility and the designed pores are favorable for cell ingrowth. The
      porous ceramics fabricated by rapid prototyping has prominent osteogenic
      differentiation activity and can be used as a choice of scaffolds for bone tissue
      engineering.

PMID- 20695374
TI  - [Bone histocompatibility of surface modified nitinol memory alloy by coating
      titanium-niobium alloy].
AB  - OBJECTIVE: Surface modification of nitinol (NiTi) shape memory alloy is an
      available method to prevent nickel ion release and coating with titanium-niobium
      (TiNb) alloy will not affect the superelasticity and shape memory of NiTi. To
      evaluate the bone histocompatibility of NiTi shape memory alloy implants coated
      by TiNb in vivo. METHODS: NiTi memory alloy columns which were 4 mm in diameter
      and 12 mm in length were coated with Ti (Ti-coating group) and TiNb alloy (TiNb
      coating group) respectively by magnetron sputtering technique. And NiTi group
      were not coated on the surface. Fifteen mongrel dogs were divided into 3 groups
      randomly with 5 dogs in each group. NiTi, Ti-coating and TiNb-coating columns
      were implanted into the lateral femoral cortex of each group, respectively. There
      were 10 columns embedded in each dog's femur whose distance was 1.0 cm to 1.5 cm
      from each other. The materials were obtained 12 months after operation. After X
      ray photography, only those columns which were perpendicular to the cortex of the
      femur shaft were selected for subsequent analysis. Push-out tests were performed
      to attain the maximum shear strength (the number of specimens of TiNi group, Ti
      coating group, and TiNb-coating group were 12, 10, and 14, respectively).
      Undecalcified sections were used for histological observation and the calculation
      of osseointegration rate (the number of specimens of TiNi group, Ti-coating
      group, and TiNb-coating group were 8, 5, and 10, respectively). RESULTS: The
      maximum shear strength of Ti-coating group (95.10 +/- 10.03) MPa, and TiNb
      coating group (91.20 +/- 15.42) MPa were significantly higher than that of NiTi
      group (71.60 +/- 14.24) MPa (P < 0.01). Gimesa staining showed that no obvious
      macrophage and inflammation cell was observed in 3 groups. The osseointegration
      rates of NiTi group, Ti-coating group, and TiNb-coating group were (21.30% +/-
      0.23%), (32.50% +/- 0.31%), and (38.60% +/- 0.58%), respectively; there were
      significant differences among 3 groups (P < 0.01). CONCLUSION: The implants of 3
      groups all have good bone histocompatibility. But the osseointegration rate and
      the shear strength in the Ti-coating group and the TiNb-coating group were better
      than those in the NiTi group, the TiNb-coating group is the best among them.

PMID- 20695375
TI  - [Treatment of spinal cord injury by mild hypothermia combined with bone marrow
      mesenchymal stem cells transplantation in rats].
AB  - OBJECTIVE: Bone marrow mesenchymal stem cells (BMSCs) play an important role in
      repairing nerve injury, meanwhile external temperature has significant effect on
      BMSCs transplantation, proliferation, and differentiation. To investigate the
      effect of BMSCs transplantation and mild hypothermia on repair of rat spinal cord
      injury (SCI). METHODS: Forty-five female adult SD rats (weighing 200-250 g) were
      made the models of hemitransection SCI and divided randomly into 3 groups
      according to different treatments: group A (SCI group), group B (BMSCs
      transplantation group), and group C [BMSCs transplantation combined with mild
      hypothermia (33-35 degrees C) group]. At 1, 2, 4, 6, and 8 weeks after injury,
      the function of hind limb was evaluated with Basso Beattie and Bresnahan (BBB)
      score and inclined plane test. At 4 weeks after injury, histopathology and BrdU
      immunohistochemistry staining were performed. At 8 weeks after injury,
      horseradish peroxidase (HRP) retrograde nerve trace and transmission electron
      microscope (TEM) testing were performed to observe the regeneration of axon.
      RESULTS: After 4 weeks, the function of hind limb obviously recovered in groups B
      and C, there were significant differences in BBB score between groups B, C and
      group A (P < 0.05), between group B and group C (P < 0.05). There was no
      significant difference (P > 0.05) in tilt angle among 3 groups after 1 and 2
      weeks, and there were significant differences (P < 0.05) among 3 groups after 4
      weeks. HE staining showed that significant cavity could be seen in group A,
      little in group B, and no cavity in group C. BrdU immunohistochemistry staining
      showed that the number of positive cells was 0, 90.54 +/- 6.23, and 121.22 +/-
      7.54 in groups A, B, and C, respectively; showing significant differences (P <
      0.01) among 3 groups. HRP retrograde neural tracing observation showed that the
      number of HRP positive nerve fibers was 10.35 +/- 1.72, 43.25 +/- 2.65, and 84.37
      +/- 4.59 in groups A, B, and C, respectively, showing significant differences (P
      < 0.01) among 3 groups. TEM observation showed that a great amount of
      unmyelinated nerve fibers and myelinated nerve fibers were found in central
      transverse plane in group C. CONCLUSION: The BMSCs transplantation play an
      important role in promotion of recovering the function of hind limb after SCI,
      and mild hypothermia has synergism effects.

PMID- 20695376
TI  - [Comparison study on injectable tissue engineered nucleus pulposus constructed by
      different cells and chitosan hydrogel].
AB  - OBJECTIVE: To compare the growth and extracellular matrix biosynthesis of nucleus
      pulposus cells (NPCs) and bone marrow mesenchymal stem cells (BMSCs) in thermo
      sensitive chitosan hydrogel and to choose seed cells for injectable tissue
      engineered nucleus pulposus. METHODS: NPCs were isolated and cultured from 3-week
      old New Zealand rabbits (male or female, weighing 150-200 g). BMSCs were isolated
      and cultured from bone marrow of 1-month-old New Zealand rabbits (male or female,
      weighing 1.0-1.5 kg). The thermo-sensitive chitosan hydrogel scaffold was made of
      chitosan, disodium beta glycerophosphate, and hydroxyethyl cellulose. Then, NPCs
      at the 2nd passage or BMSCs at the 3rd passage were mixed with chitosan hydrogel
      to prepare NPCs or BMSCs-chitosan hydrogel complex as injectable tissue
      engineered nucleus pulposus. The viabilities of NPCs and BMSCs in the chitosan
      hydrogel were observed 2 days after compound culture. The shapes and
      distributions of NPCs and BMSCs on the scaffold were observed by scanning
      electron microscope (SEM) 1 week after compound culture. The histology and
      immunohistochemistry examination were performed. The expressions of aggrecan and
      collagen type II mRNA were analyzed by RT-PCR 3 weeks after compound culture.
      RESULTS: The thermo-sensitive chitosan hydrogel was liquid at room temperature
      and solidified into gel at 37 degrees C (after 15 minutes) due to crosslinking
      reaction. Acridine orange/propidium iodide staining showed that the viability
      rates of NPCs and BMSCs in chitosan hydrogel were above 90%. The SEM observation
      demonstrated that the NPCs and BMSCs distributed in the reticulate scaffold, with
      extracellular matrix on their surfaces. The results of HE, safranin O histology
      and immunohistochemistry staining confirmed that the NPCs and BMSCs in chitosan
      hydrogel were capable of producing extracellular matrix. RT-PCR results showed
      that the expressions of collagen type II and aggrecan mRNA were 0.564 +/- 0.071
      and 0.725 +/- 0.046 in NPCs culture with chitosan hydrogel, and 0.713 +/- 0.058
      and 0.852 +/- 0.076 in BMSCs culture with chitosan hydrogel; showing significant
      difference (P < 0.05). CONCLUSION: The thermo-sensitive chitosan hydrogel has
      good cellular compatibility. BMSCs culture with chitosan hydrogel maintains
      better cell shape, proliferation, and extracellular matrix biosynthesis than
      NPCs.

PMID- 20695377
TI  - [Differentiation of bone marrow mesenchymal stem cells into nucleus pulposus-like
      cells transfected by SOX9 eukaryotic expression vector in vitro].
AB  - OBJECTIVE: The biological treatment of intervertebral disc degeneration becomes a
      research hotspot in recent years. It is necessary to find an effective approach
      to induce bone marrow mesenchymal stem cells (BMSCs) differentiate to disc cells
      which could make application of cell transplantation as a treatment of
      intervertebral disc degeneration. To investigate the effects of the recombinant
      plasmid pcDNA3.1IE-SOX9Flag on differentiation of rabbit BMSCs into nucleus
      pulposus-like cells. METHODS: The eukaryotic expression vector of pcDNA3.1IE
      SOX9Flag was constructed. Rabbit BMSCs were isolated and cultured from one-month
      old New Zealand white rabbits and were induced into osteogenetic cells in the
      osteogenesis supplement medium; and the cell surface markers were detected by
      flow cytometry. The cells at the 3rd passage were randomly divided into 3 groups:
      in transfected group, the cells were transfected with recombinant plasmid
      pcDNA3.1IE-SOX9Flag; in negative control group, the cells were transfected with
      plasmid pcDNA3.1; and in blank control group, the cells were treated with the
      media without recombinant plasmid. After selected by G418 for 7 days, the cells
      were harvested and RT-PCR was employed to assay SOX9 mRNA and collagen type II
      gene (Col2al) mRNA expressions in BMSCs. The expression of SOX9 protein was
      assayed by Western blot and collagen type II expression was also observed by
      immunohistochemical staining. RESULTS: The SOX9 eukaryotic expression vector was
      constructed successfully. The BMSCs after 5 days of osteogenetic induction were
      positive for the alkaline phosphatase staining. What was more, CD44 expression
      was positive but CD34 and CD45 expressions were negative. The transfection
      efficiency was 34.32% +/- 1.75% at 72 hours after transfection. After 2 weeks of
      transfection, BMSCs turned to polygonal and elliptical. And the cell
      proliferation was gradually slow which was similar to the growth characteristic
      of nucleus pulposus cells. RT-PCR identification showed that SOX9 mRNA and Col2al
      mRNA expressions were positive in transfected group, and were negative in 2
      control groups. Western blot detection showed that SOX9 protein expressed in
      transfected group but did not express in the control groups. At 2 weeks after
      transfection, the result of the immunohistochemical staining for collagen type II
      was positive in transfected group. CONCLUSION: The recombinant plasmid pcDNA3.1IE
      SOX9Flag can be successfully transfected into rabbit BMSCs, the transfected BMSCs
      can differentiate into nucleus pulposus-like cells, which lays a theoretical
      foundation for treatment of intervertebral disc degeneration with BMSCs
      transplantation.

PMID- 20695378
TI  - [Strain-induced tenogenic differentiation of bone marrow mesenchymal stem cells].
AB  - OBJECTIVE: To study the possibility of bone marrow mesenchymal stem cells (BMSCs)
      differentiation into tenocytes (TCs) under strain stimulation by co-culture of
      BMSCs-small intestinal submucosa (SIS) composites in vitro. METHODS: BMSCs were
      isolated by adherent culture from the bone marrow of 1-week-old SD rats. Inducing
      method of multiple differentiation and flow cytometry were applied to identify
      the cells. The stress-strain curve of SIS was measured with Instron machine.
      Purified BMSCs (2nd passage, 2.5 x 10(5) cells/cm2) were seeded on SIS (3 cm x 1
      cm at size) and cultured for 2 days and then continued for another 5 days under
      strain stimulation (stretching frequency was 0.02 Hz, action time was 15
      minutes/hour and 12 hours/day, strain amplitude was 5%) as experimental group,
      while the BMSCs-SIS composites were sustained static culture as control group.
      TCs were isolated from tail of 1-week-old SD rats. TCs-SIS composites were
      cultured under non-strained as positive control group. Scanning electron
      microscope (SEM) was used to examine the morphological changes of BMSCs after
      strain stimulation. The contents of Scleraxis and Tenomodulin in supernatant were
      tested by ELISA kit. Results The BMSCs could be induced to differentiate into
      osteoblasts and lipocytes, and showed the results of CD34-, CD45-, and CD90+,
      which were accorded with the biological characteristics of BMSCs. The failure
      test of SIS showed that the average elastic strain was 39.5%. SEM observation
      showed that the strain-stimulated BMSCs had the TCs-like morphological
      characteristics. The contents of Scleraxis and Tenomodulin in supernatant of
      experimental group, control group, and positive control group were (3.56 +/-
      0.91) micromol/L and (4.27 +/- 1.10) micromol/L, (0.23 +/- 0.14) micromol/L and
      (0.16 +/- 0.10) micromol/L, and (14.73 +/- 2.30) micromol/L and (10.65 +/- 1.51)
      micromol/L, respectively. There were significant differences among 3 groups (P <
      0.05). CONCLUSION: Appropriate strain stimulation could induce BMSCs
      differentiate into TCs, and the best conditions of strain stimulation need more
      experiments.

PMID- 20695379
TI  - [Recombinant human insulin gene lentivirus transfecting human umbilical cord
      mesenchymal stem cells in vitro].
AB  - OBJECTIVE: To construct the lentiviral vector to co-express enhanced green
      fluorescent protein (EGFP) gene and human insulin (insulin) gene, and to explore
      the condition to transfect human umbilical cord mesenchymal stem cells (hUCMSCs)
      so as to lay a foundation for tissue engineered adipose reconstruction and
      transplantation in vivo in future. METHODS: The insulin gene was cloned to
      lentiviral expression vector with EGFP [pLenti6.3-internal ribosome entry site
      (IRES)-EGFP] by recombinant DNA technology, the positive clones were screened,
      and lentiviral packaged systems and target gene plasmid were co-transfected to
      package virus in 293T cells by lipofectin. The reporter gene expression was
      observed by fluorescent inverted phase contrast microscope, virus supernatant was
      collected, purified and concentrated, and the titer of recombinant viruses was
      determined, hUCMSCs from umbilical cord tissue of mature neonates were isolated
      and cultured by different multiple of infection (MOI, 0, 1, 3, 5, 7, 10, 15, and
      20). By recombinant lentiviral infected hUCMSCs with reporter gene green
      fluorescent protein expression, the best MOI was screened; recombinant lentiviral
      infected hUCMSCs at the best MOI, then real-time PCR and Western blot methods
      were applied to detect insulin gene and insulin protein expression levels in
      cells. RESULTS: The recombinant lentiviral vector of co-expressing insulin gene
      and EGFP gene (pLenti6.3-insulin-IRES EGFP) was successfully constructed. Virus
      could be packaged, purified and concentrated successfully. The virus titer was
      1.3 x 10(8) TU/mL. The best MOI was 10 and the transfer efficiency was up to 90%
      in the same time. Real-time PCR results showed that insulin gene expression of
      transfected group was positive and non-transfected group was negative; Western
      blot detection confirmed that insulin protein expression of transfected group was
      positive in cells and supernatant, but that of non-transfected group was both
      negative. CONCLUSION: Lentiviral vector pLenti6.3-insulin-IRES-EGFP carrying
      recombinant insulin gene could effectively transfect hUCMSCs and express insulin
      protein.

PMID- 20695380
TI  - [An experimental study on rabbit bone marrow mesenchymal stem cells double
      labeled by PKH26 and 5-bromo-2'-deoxyuridine in vitro and application in cardiac
      patch].
AB  - OBJECTIVE: To study the biological characteristic of rabbit bone marrow
      mesenchymal stem cells (BMSCs) double-labeled by PKH26 and BrdU in vitro, and to
      construct tissue engineered cardiac patch in vitro. METHODS: The BMSCs were
      harvested from 6-month-old New Zealand rabbits and labeled with PKH26 and BrdU.
      The growth and fluorescent intensity were observed by inverted phase contrast
      microscope, fluorescent microscope, flow cytometry, and MTT detection. The
      characteristics of double-labeled BMSCs differentiating into osteoblasts and
      adipocytes, respectively, in vitro were identified by alkaline phosphatase (ALP)
      staining, Alizarin red staining, Oil red O staining, immunocytochemical technique
      of collagen type I, and osteocalcin expression. The labeled BMSCs were seeded on
      the small intestinal submucosa (SIS) and co-cultured for 5-7 days to construct
      tissue engineered cardiac patch. The patches were tested by inverted phase
      contrast microscope, fluorescent microscope, scanning electron microscope, and HE
      staining to observe the cell proliferation. RESULTS: The double-labeled cells
      grew well and showed red fluorescence. There was no significant difference in the
      growth characteristic between the labeled and unlabeled cells. There was no
      significant difference in the expression of stem cell specific surface antigen
      between before labeling and after labeling. After osteogenic induction of labeled
      BMSCs, ALP staining and Alizarin red staining were positive, and the cells
      expressed collagen type I and osteocalcin. After adipocytes induction, lipid
      droplets could be observed in cytoplasm by Oil red O staining. After the co
      culture in vitro for 5-7 days, the double-labeled cells grew well, showing a
      multi-layer cellular structure on the surface of SIS. CONCLUSION: Rabbit BMSCs
      can be double-labeled with PKH26 and BrdU stably. The labeled cells still have
      the potential of self-renewal ability and multi potent differentiation ability;
      tissue engineered cardiac patch can be constructed by co-culturing labeled BMSCs
      and SIS in vitro.

PMID- 20695381
TI  - [Experimental study on effect of monocyte chemoattractant protein 1 on migration
      of induced and differentiated mouse bone marrow mesenchymal stem cells in vitro].
AB  - OBJECTIVE: To investigate the effect of monocyte chemoattractant protein 1 (MCP
      1) on the migration of the induced and differentiated mouse bone marrow
      mesenchymal stem cells (BMSCs) for raising the efficacy of intravenous
      transplantation of BMSCs. METHODS: The BMSCs were cultured with the method of
      differential adhesion and density gradient centrifugation of C57/BL10 mice, and
      were identified by alkaline phosphatase Gomori modified staining after osteogenic
      inducing. At the 3rd passage, the BMSCs were induced to the myoblasts with 5
      azacytidine (5-Aza). The chemotaxis of MCP-1 in the induced and differentiated
      BMSCs in vitro at concentrations of 25, 50, 100, 200, and 400 ng/mL was observed
      through the migration test, by counting the number of the migrated cells. The
      expression of the chemokine receptor 2 (CKR-2) in the induced and differentiated
      BMSCs was detected with the flow cytometry. RESULTS: The cells could be cultured
      with the methods of differential adhesion and density gradient centrifugation and
      still had higher proliferative and differentiative potency; the induced cells at
      the 3rd passage could differentiate to the osteoblasts, confirming that the cells
      were BMSCs; the myogenic induced BMSCs possessed the sarcotubule structure. The
      number of the migrating BMSCs at MCP-1 concentrations of 25-400 ng/mL were
      respectively 35.066 7 +/- 6.584 2, 43.200 0 +/- 6.460 8, 44.466 7 +/- 4.823 5,
      45.600 0 +/- 8.650 3, and 50.733 3 +/- 7.582 5; showing significant difference
      when compared with control group (28.333 3 +/- 8.917 6, P < 0.05), and presenting
      significant difference among 25, 50, 400 ng/mL groups compared with each other (P
      < 0.05). The expression of CKR-2 in the mouse BMSCs (48.0%) was significantly
      higher (P < 0.001) than those of blank control (0.6%) and negative control
      (17.0%). CONCLUSION: The results indicate that the MCP-1 can induce the migration
      of mouse BMSCs by MCP-1/CKR-2 pathway.

PMID- 20695382
TI  - [Differentiation of human embryonic stem cells into hepatocyte-like cells in an
      adherent culture system with single-step induction].
AB  - OBJECTIVE: To establish a new induction method from human embryonic stem cells
      (hESCs) differentiating into hepatocyte-like cells using an adherent culture
      system with single-step induction. METHODS: Undifferentiated hESCs were cultured
      on Matrigel-coated culture plates for 4 days, hepatic differentiation was
      initiated at 60%-70% confluence by adding Activin A for 5 days. Then the
      induction medium was replaced by hepatocyte induction medium (HIM) supplemented
      with fibroblast growth factor 1 (FGF-1) and bone morphogenetic protein 4 (BMP-4)
      for another 6 days. Finally, the cells were treated with HIM adding hepatocyte
      growth factor (HGF) and Oncostatin M (OSM) for 5-7 days. The characteristics of
      differentiated cells were determined by morphology, immunofluorescence staining,
      RT-PCR, and Periodic acid-Schiff (PAS) test. RESULTS: Differentiated cells
      treated with Activin A, FGF-1, BMP-4, HGF, and OSM sequentially were
      morphologically larger and became spherical, oval or polygon. Some cells had 2 or
      3 nuclei, suggesting that the cells have a hepatocyte-like morphology.
      Differentiated cells at first induction stage could be stained positive by SOX17
      and Forkhead (FOX)A2 after induction by Activin A. Then they turned to be a
      fetoprotein (AFP) and al antitrypsin positive cells at second induction stage
      after induction by FGF-1 and BMP-4. Finally, the differentiated cells treated
      with HGF and OSM showed PAS positive for glycogen detection. The differentiated
      cells at various stages also expressed at early (SOX17, FOXA2, and GATA-4),
      middle (AFP, albumin, and cytokeratin 18), and mature (alcohol dehydrogenase 1C
      and Cytochrome P4501B1) stage hepatic genes, respectively. CONCLUSION: Using a
      simple-step induction method and by supplied with cytokines consequently, hESCs
      can be induced to differentiate into hepatocyte-like cells. The differentiation
      method can provide seed cells for hepatic tissue engineering or cell-therapy.

PMID- 20695383
TI  - [Preparation of decellularized carotids and its biocompatibility].
AB  - OBJECTIVE: To study the preparation method for acellular vascular matrix and to
      evaluate its biocompatibility and safety so as to afford an ideal scaffold for
      tissue engineered blood vessel. METHODS: Fresh caprine carotids (length 50 mm)
      were harvested and treated with repeated frozen (-80 degrees C)/thawing (37
      degrees C), cold isostatic pressing (506 (MPa, 4 degrees C), and 0.125% sodium
      dodecyl sulfate separately for preparation of acellular vascular matrix.
      Fluorescence staining and DNA remain test were used to assess the cell extracting
      results. Biological characteristics were compared with the raw caprine carotids
      using HE staining, Masson staining, scanning electron microscope (SEM), and
      mechanical test. Biocompatibility was detected using cell adhesion test, MTT
      assay, and subcutaneously embedding test. Ten SD rats were divided in 2 groups (n
      = 5). In experimental group, acellular vascular matrix preserved by the
      combination of repeated frozen/thawing, ultrahigh pressure treatment and chemical
      detergent was subcutaneously embedded; and in control group, acellular vascular
      matrix preserved only by repeated frozen/thawing and ultrahigh pressure treatment
      was subcutaneously embedded. RESULTS: HE staining and Masson staining revealed
      that no nucleus was detected in the acellular vascular matrix. SEM demonstrated
      that a lot of collagen fibers were preserved which were beneficial for cell
      adhesion. Fluorescence staining and DNA remain test showed that the cells were
      removed completely. There was no significant difference in stress and strain
      under the maximum load between before and after treatment. Mechanical test
      revealed that the acellular vascular matrix reserved mechanical properties of the
      raw caprine carotids. Cell adhesion test and MTT assay confirmed that
      cytotoxicity was grade 0-1, and the acellular vascular matrix had good
      compatibility to endothelial cells. After subcutaneously embedding for 8 weeks,
      negligible lymphocyte infiltration was observed in experimental group but obvious
      lymphocyte infiltration in control group. CONCLUSION: The acellular vascular
      matrix, which is well-preserved by the combination of repeated frozen/thawing,
      ultrahigh pressure treatment, and chemical detergent, is an ideal scaffold for
      tissue engineered blood vessel.

PMID- 20695385
TI  - [Research progress of full-thickness tissue engineered skin].
AB  - OBJECTIVE: To review the latest research progress of full-thickness tissue
      engineered skin (FTTES), to thoroughly understand its current state of research
      and application so as to lay a solid foundation for developing new type FTTES and
      improving the quality of skin substitutes. METHODS: Domestica and international
      literature concerning FTTES in recent years was extensively reviewed and
      comprehensively analyzed. RESULTS: Some progress of FTTES had made in seed cells,
      scaffold materials and construction, and some therapeutic efficacy had also been
      achieved in clinical application. But FTTES grafting successful rate was lower,
      and it had no complete skin structure and had not reached the requirements of
      clinical application. CONCLUSION: FTTES is an ideal skin substitute and has great
      development prospects. However, in seed cells, scaffold materials, construction
      and applications of FTTES, further studied is still needed.

PMID- 20695384
TI  - [Research and application of functional tissue engineered tendons].
AB  - OBJECTIVE: To review the research and application of functional tissue engineered
      tendons (FTETs). METHODS: Recent literature concerning the research of FTETs was
      reviewed and analyzed. RESULTS: Functional tissue engineering (FTE) was a new
      approach that placed an emphasis on the importance of mechanical stress in
      determining the success of tissue engineered constructs and the effect of tissue
      remodeling in vivo. The concept of FTE was introduced into the research of tissue
      engineered tendons; by measuring in vivo loads of normal tendon and using the
      information as a guideline, the appropriate tissue engineered tendon which can
      withstand in vivo loads was designed. It would be possible to solve the problems
      that the biomechanical function of the tissue engineered tendons could not meet
      the requirements of the loading environment in vivo. CONCLUSION: FTETs have a
      more promising future for the treatment of tendon defects.

PMID- 20695386
TI  - [Research progress of tissue engineered nerve grafts].
AB  - OBJECTIVE: To summarize the recent advance in the research of tissue engineered
      nerve grafts. METHODS: The clinical and experimental research papers about tissue
      engineered nerve grafts were extensively reviewed and analyzed. RESULTS: The
      porosity, mechanical property and surface topography of a nerve scaffold, which
      was either made up of natural biodegradable polymers or synthetic polyesters,
      were pivotal factors that influenced the capacity of the scaffold in supporting
      nerve regeneration. Of various candidate supporting cells for nerve tissue
      engineering, the bone marrow mesenchymal stem cells had been paid more attention
      because of their advantages. Several model designs of drug delivery systems for
      controlled release of growth factors had been attempted. In clinical settings,
      short nerve gaps were demonstrated to be treatable with several nerve conduits
      which were commercially available, with functional recovery approximating to
      nerve autografting. CONCLUSION: The field of nerve tissue engineering has
      witnessed a rapid development not only in experimental research but also in
      clinical application.

PMID- 20695387
TI  - [An experimental study on antimicrobial efficacy of platelet-rich plasma for bone
      infection prophylaxis].
AB  - OBJECTIVE: Platelet-rich plasma (PRP) contains high concentrations of platelets
      and leucocytes, which play a key role in antimicrobial host defense system. To
      evaluate the antimicrobial efficacy of autologous PRP in vitro and in vivo and to
      explore the mechanism of action so as to provide the experimental basis for the
      prevention and treatment of bone infection. METHODS: PRP was prepared with the
      method of two centrifugation from 15 health volunteers. Platelet-leukocyte gel
      (PLG) was obtained after activation of PRP with bovine thrombin. Next, PLG was
      incubated with Staphylococcus aureus (1 x 10(6) cfu/mL) in vitro compared with
      PRP, platelet-poor plasma (PPP) and PBS. Samples were taken out after 2, 4, 6, 8,
      12, and 24 hours for bacterial culture and colony count. Thirty-six New Zealand
      adult rabbits, weighing (2.85 +/- 0.11) kg, were divided into 4 groups: PLG (n =
      10), antibiotic (n = 10), infection (n = 10), and PBS (n = 6) groups. The
      osteomyelitis models were made by injecting 0.1 mL Staphylococcus aureus
      suspension (1 x 10(6) cfu/mL) into the tibial canal in PLG group, antibiotic
      group, and infection group; equal volumes of PBS was injected in PBS group as a
      control. Autologous PLG was injected immediately after operation in PLG group.
      Cefazolin (30 mg/kg) was injected through the auricular vein from 1 hour before
      operation to 72 hours after operation in antibiotic group, once per 8 hours. No
      treatment was given in infection and PBS groups. The efficacy of PLG for
      osteomyelitis prophylaxis was evaluated by microbiological, X-ray and
      histological observation within 28 days. RESULTS: The contents of leucocyte and
      platelet of PRP were 6.2 times and 5.5 times of whole blood, showing significant
      differences (P < 0.05); the contents of leucocyte and platelet of PPP were
      significantly lower than those of whole blood and PRP (P < 0.05). In vitro test
      showed that PLG had the most obvious bacteriostasis effect. The bacterial count
      reached a minimum value at 4 hours after incubation in PLG and at 6 hours after
      incubation in PRP. PPP had slow and no obvious bacteriostasis effect and PBS had
      no bacteriostasis effect. At 2, 4, 6, 8, 12, and 24 hours of incubation, the
      bacterial count reduced significantly when compared PLG with PRP and PPP (P <
      0.05), when compared PRP with PPP (P < 0.05). In PLG group and antibiotic group,
      1 rabbit died, respectively; 34 rabbits survived to the end of the experiment.
      There was no significant difference (P > 0.05) in temperature, body weight,
      erythrocyte sedimentation rate and content of leucocyte between 28 days after
      operation and before operation in 4 groups. After 28 days, the X-ray scores were
      2.78 +/- 1.39, 1.55 +/- 1.48, 4.17 +/- 1.25, and 0 in PLG, antibiotic, infection,
      and PBS groups, respectively, which was significantly higher in infection group
      than in other 3 groups (P < 0.05). Also, the histological scores were 5.89 +/-
      3.92, 3.00 +/- 2.31, 10.33 +/- 4.03, and 0, respectively, which was significantly
      higher in infection group than in other 3 groups (P < 0.05), and was
      significantly lower in antibiotic group than in PLG group (P < 0.05). The results
      of bacterial culture showed that the infection rates of PLG group (44.4%) and
      antibiotic group (20.0%) were significantly lower (P < 0.05) than that of
      infection group (88.9%). The quantitative analysis of bacteria showed that the
      number of bacteria was signficantly lower (P < 0.05) in PLG and antibiotic groups
      than in infection group. CONCLUSION: PRP forms into PLG after activating, it can
      inhibit Staphylococcus aureus reproduction in vitro and can effectively prevent
      bone infection in vivo.

PMID- 20695388
TI  - [Effect of brominated furanones on biofilm formation of Escherichia coli on
      polyvinyl chloride material].
AB  - OBJECTIVE: To study the influence of brominated furanones on the biofilm
      formation of Escherichia coli on the polyvinyl chloride (PVC) material, and to
      provide new ideas for the research of surface modification of materials and
      clinical treatment of biomaterial centered infection. METHODS: Three brominated
      furanones with representative chemical structure were chosen and coated on the
      surface modification of PVC materials, respectively [furanone 1: 3, 4-dibromo-5
      hydroxy-furanone; furanone 2: 4-bromo-5-(4-methoxyphenyl)-3-(methylamino)
      furanone; furanone 3: 3, 4-dibromo-5, 5-bis (4-methylphenyl)-2 (5H)-furanone].
      All the modificated PVC materials and Escherichia coli were co-cultivated. The
      PVC material soaked with 75% ethanol for 5 minutes and Escherichia coli were co
      cultivated together as the control group. The thickness of bacterial community
      and bacterial community quantity in the unit area on PVC materials were measured
      by confocal laser scanning microscope (CLSM), and the surface structure of
      biofilm formation was observed by scanning electron microscope (SEM). RESULTS:
      The CLSM showed that the thickness of bacterial community and the bacterial
      community quantity in the unit area of PVC materials was significantly less (P <
      0.05) in furanone 3 group than in control group, but no significant difference (P
      > 0.05) was found between furanone 1, furanone 2 groups and control group. SEM
      showed that the quantity of bacterial community in the unit area of PVC materials
      surface in furanone 3 group was fewer than that in control group at 6 hours; the
      biofilm structure on PVC materials surface formed at 18 hours in control group,
      furanone 1 group, and furanone 2 group, but there was no mature biofilm structure
      on PVC materials surface in furanone 3 group at 18 hours. CONCLUSION: The impact
      of different brominated furanones on Escherichia coli biofilm formation on the
      surface of PVC materials is different, 3, 4-dibromo-5, 5-bis (4-methylphenyl)-2
      (5H)-furanone can inhibit Escherichia coli biofilm formation on the surface of
      PVC material. Polyvinyl chloride

PMID- 20695389
TI  - [Arthroscopical subtalar arthrodesis for malunion of calcaneal fractures].
AB  - OBJECTIVE: To evaluate the clinical results of arthroscopical subtalar
      arthrodesis for malunion of calcaneal fractures. METHODS: Between July 2006 and
      December 2008, 12 cases of malunion of calcaneal fractures were treated with
      arthroscopical subtalar arthrodesis, including 10 males and 2 females with an age
      range of 38-54 years (44.8 years on average). The location was left side in 5
      cases and right side in 7 cases. The injury was caused by falling from height in
      8 cases, by traffic accident in 3 cases, and other in 1 case. It was 3-7 months
      from injury to operation. All cases were classified as Stephens type II. The
      total score was 35.68 +/- 10.35 and the pain score was 8.14 +/- 1.83 before
      operation according to Hindfoot scores system of American Orthopaedic Foot &
      Ankle Society (AOFAS). RESULTS: All incisions achieved primary healing and the
      patients were all followed up 14-32 months (18 months on average). The X-ray
      films showed bony fusion after 10-14 weeks (11.5 weeks on average). The total
      score was 76.45 +/- 9.83 and the pain score was 1.52 +/- 1.48 after operation
      according to Hindfoot scores system of AOFAS, showing significant difference when
      compared with those before operation (P < 0.01). CONCLUSION: Arthroscopical
      subtalar arthrodesis can get satisfactory fusion rate with few complications for
      malunion of calcaneal fractures.

PMID- 20695390
TI  - [Analysis of diagnosis and treatment of talus lateral process fracture].
AB  - OBJECTIVE: To analyse and summarize the diagnosis, treatment, and clinical
      effects of talus lateral process fracture. METHODS: Between February 2001 and
      March 2009, 21 male patients with an average age of 33.6 years (range, 18-46
      years) with talus lateral process fractures were treated. Fracture was caused by
      falling from height in 18 cases, by tumbling in 2 cases, and by sprain in 1 case.
      According to Hawkins classification, there were 4 cases of type I, 15 cases of
      type II, and 2 cases of type III, all being closed fractures. The disease course
      was from 2 hours to 26 days. In 17 patients whose fracture fragments were more
      than 1 cm x 1 cm x 1 cm or whose fracture fragments shifting was more than 1 mm,
      open reduction and internal fixation with AO hollow titanium nails were performed
      in 14 patients, open reduction and internal fixation with door-shape self-made
      nail in 1 patient, and open reduction and internal fixation with absorbable
      screws in 2 patients. In 4 patients whose fracture fragments were less than 0.6
      cm x 0.5 cm x 0.5 cm or whose fracture fragments shifting was less than 1 mm,
      fragments removal was performed in 2 patients, Kirschner pins in 1 patient, and
      plaster conservative therapy in 1 patient. In patients with ligaments injury, the
      ligaments was reconstructed during the operation. RESULTS: All the incisions
      achieved primary healing. Twenty-one patients were followed up 9.5 months to 8
      years. No ankle pain occurred and the range of joint motion was normal after
      operation. The X-ray films showed that all cases achieved fracture union. And the
      healing time was from 8 weeks to 14 weeks (10 weeks on average). According to
      American Orthopaedic Foot & Ankle Society (AOFAS) for foot, the results were
      excellent in 17 cases, good in 3 cases, and moderate in 1 case; the excellent and
      good rate was 95.24%. CONCLUSION: The size and displacement of fracture fragment
      should be considered first in the treatment of lateral process fracture of talus;
      in patients who are complicated by lateral malleolus ligament injury, the
      ligament should be reconstructed to avoid the chronic non-stability of lateral
      ankle.

PMID- 20695391
TI  - [Surgical treatment of proximal femoral malignant tumors].
AB  - OBJECTIVE: To evaluate the clinical outcomes of the wide resection and the
      functional reconstruction for treating malignant tumors of the proximal femur.
      METHODS: The clinical data were analysed from 62 patients with malignant tumors
      of the proximal femur treated between January 1987 and December 2007. There were
      29 males and 33 females with a median age of 35 years (range, 14-73 years). In 41
      patients with primary malignant tumors having a disease course of 0.5-14.0
      months, there were 16 cases of osteosarcoma, 7 cases of fibrosarcoma, 6 cases of
      chondrosarcoma, 6 cases of malignant fibrous histiocytoma, 4 cases of mesenchymal
      sarcoma,1 case of Ewing sarcoma, and 1 case of angiosarcoma, including 3 cases of
      type IB, 2 cases of type IIA, 35 cases of type IIB, and 1 case of type III
      according to Enneking stage. In 21 patients with metastatic tumors, 16 had a
      malignant tumor history; the disease course was 0.1-28.0 months (3.4 months on
      average). Radical resection was performed in 9 cases, extensive resection in 39
      cases, and marginal resection in 14 cases. After resection, 39 cases underwent
      reconstruction with prostheses (prostheses group) and 14 cases underwent
      reconstruction with allograft-prosthetic composites (APC, APC group). RESULTS:
      All incision healed by first intention. Twenty-six cases died of tumor
      metastasis, their postoperative survive time was 16-56 months (28 months on
      average). The average follow-up time was 64 months (range, 28-221 months) in 36
      survival patients. The local recurrence rate of primary malignant tumors was
      4.88% (2/41). In prostheses group, dislocation of femoral head occurred in 2
      cases, fracture of prosthetic stem in 1 case, hip pain in 3 cases, acetabular
      wear in 3 cases, and stem loosening in 5 cases. In APC group, nonunion of APC
      occurred in 3 cases and acetabular wear in 1 case. At last follow-up, the average
      Musculoskeletal Tumor Society (MSTS) functional scores were 77.69% +/- 6.50% in
      prostheses group and 85.71% +/- 7.45% in APC group, showing significant
      difference (P < 0.001). CONCLUSION: When the wide resection is performed for
      malignant tumors of the proximal femur, better local control could be achieved.
      Compared with reconstruction of the prosthesis, the APC reconstruction can
      provide better function.

PMID- 20695392
TI  - [Spinal wedge osteotomy by posterior approach for correction of severe rigid
      scoliosis].
AB  - OBJECTIVE: To introduce operation skill of the spinal wedge osteotomy by
      posterior approach for correction of severe rigid scoliosis and to discuss the
      selection of the indications and the range of fusion and fixation. METHODS:
      Between July 1999 and January 2009, 23 patients with severe rigid scoliosis were
      treated with spinal wedge osteotomy by posterior approach, including 16
      congenital scoliosis, 5 idiopathic scoliosis, and 2 neurofibromatosis scoliosis.
      There were 11 males and 12 females with a median age of 15 years (range, 8-29
      years). Two patients had previous surgery history. The Cobb's angles of scoliosis
      and kyphosis before operation were (85.39 +/- 13.51) degrees and (56.78 +/-
      17.69) degrees, respectively. The mean spinal flexibility was 14.4% (range, 4.7%
      22.5%). The trunk shift was (15.61 +/- 4.89) mm. The preoperative CT or MRI
      showed bony septum in the canal in 2 patients. RESULTS: The mean operative time
      was 241 minutes and the mean blood loss was 1 452 mL. The average fused vertebrae
      were 10.7 segments (range, 8-14 segments). The follow-up ranged from 1 to 4 years
      with an average of 2 years and 6 months. The postoperative Cobb's angle of
      scoliosis was (38.70 +/- 6.51) degrees, the average correction rate was 54.7%.
      The postoperative Cobb's angle of kyphosis was (27.78 +/- 6.01) degrees, the
      average correction rate was 51.0%. The trunk shift was improved to (4.69 +/-
      1.87) mm, the increased height was 5.2 cm on average (range, 2.8-7.7 cm). The
      Cobb's angle of scoliosis was (41.57 +/- 6.80) degrees with an average 2.9
      degrees loss of correction at the final follow-up; the Cobb's angle of kyphosis
      was (30.39 +/- 5.94) degrees with an average 2.6 degrees loss of correction at
      the final follow-up; the trunk shift was (4.78 +/- 2.00) mm at the final follow
      up. There were significant differences (P < 0.05) in the Cobb's angles of
      scoliosis and kyphosis and the trunk shift between preoperation and
      postoperation, between preoperation and last follow-up. Four cases had pedicle
      fracture, 1 had Li nerve root injury, 2 had superior mesenteric artery syndrome,
      1 had exudates of incision, and 2 had temporary dysfunction of both lower
      extremity. CONCLUSION: Spinal wedge osteotomy by posterior approach is a reliable
      and safe surgical technique for correcting severe rigid scoliosis. With segmental
      pedical screw fixation, both the spinal balance and stability can be restored.

PMID- 20695393
TI  - [Complex of auto-cartilage grafting and silicone implant for open nasal plasty].
AB  - OBJECTIVE: To investigate the surgical methods and outcome of reshaping the nose
      by using autologous cartilage grafting-silicone gel complex combined with
      trimming the lower lateral cartilages and thinning the superfluous tissue of the
      tip. METHODS: Between May 2006 and July 2008, 36 patients with ugly nose shape
      received open nasal plasty by thinning the superfluous tissue and trimming the
      lower lateral cartilages combined with implant of auto-cartilage and silicone gel
      complex. There were 3 males and 33 females with an average age of 23 years
      (range, 18-36 years), including 20 cases of hypertrophy and obtuse round of nasal
      tip, 10 cases of flat of nasal tip, 2 cases of slight nostril exposure, and 4
      cases of small whole nose with hypertrophy of nasal tip. Among them, 8 cases
      received 2-time operations. RESULTS: All incisions achieved healing by first
      intention. No deformation and complication occurred at donor sites of cartilage.
      The appearance, contour, color, and touch sensation of the nose were satisfactory
      and no complications of prosthesis exposure and skin redness of the nasal tip
      occurred. At 3-5 months after operation, the appearance of the nasal tip was
      satisfactory when part of the soft tissue was absorbed. Thirty-two patients were
      followed up 3-12 months (6 months on average), who were satisfied with the
      appearance of nose with good correct rate. CONCLUSION: Nasal plasty by using auto
      cartilage grafting and silicone implant combined with trimming the lower lateral
      cartilages and thinning the superfluous tissue of the tip is an effective method
      especially for round or bulbous nasal tip.

PMID- 20695394
TI  - Sharing cases: the Observationes in early modern medicine.
AB  - This paper examines the rise of an epistemic genre, the Observationes, a new form
      of medical writing that emerged in Renaissance humanistic medicine. The
      Observationes (collections of case-histories) originated in the second half of
      the sixteenth century, grew rapidly over the course of the seventeenth, and had
      become a primary form of medical writing by the eighteenth century. The genre
      developed initially as a form of self-advertisement by court and town physicians,
      who stressed success in practice, over and above academic learning, as a core
      element of their professional identity. This unprecedented emphasis on practice
      as a source of knowledge remained a key feature of the Observationes in its
      subsequent development. As the genre evolved, the original emphasis on
      therapeutic success gave way to a new focus on the descriptive knowledge of
      disease through detailed observation. The authorial identity projected by the
      writers of Observationes was increasingly that of the learned and experienced
      observer, bent on comparing notes and sharing his cases with the fellow members
      of the res publica medica. This paper charts the development of the genre,
      examining how its growth contributed to the new epistemological value of
      observation in the age of the Scientific Revolution.

PMID- 20695395
TI  - Julius Caesar Scaliger on plant generation and the question of species constancy.
AB  - The sixteenth-century physician and philosopher Julius Caesar Scaliger combines
      the view that living beings are individuated by a single substantial form with
      the view that the constituents of the organic body retain their identity due to
      the continued existence and operation of their own substantial forms. This essay
      investigates the implications of Scaliger's account of subordinate and dominant
      substantial forms for the question of the constancy of biological species.
      According to Scaliger, biological mutability involves not only change on the
      ontological level of accidents but, in some cases, also change on the level of
      substantial forms. While he shares the received view that substantial forms
      themselves cannot undergo change, he maintains that relations of domination and
      subordination between substantial forms can undergo change. He uses his theory of
      how such changes can occur to explain cases of revertible plant degeneration.
      Moreover, in his view plants that belong to previously unknown biological species
      can emerge from changes in the relations between the many forms contained in
      plant seeds.

PMID- 20695396
TI  - Iatrosophia and an eighteenth-century oneirokrites in the National Library of
      Greece.
AB  - Medical dreams were not discussed by Greek popular dream interpreters, but were
      the domain of physicians like Hippocrates, Galen, and Rufus of Ephesus, or the
      followers of the healing god Asclepius. An exception is an oneirokrites
      (dreambook) in Codex 1350 of the National Library of Greece in Athens. This
      eighteenth-century text reflects Ottoman Greek iatrosophia. An iatrosophion,
      widely used in Byzantine and Ottoman Greece, was a physician's notebook of
      recipes and treatments or was the collective compendium of classical and
      Byzantine medical and pharmacological texts consulted in hospital settings. Some
      iatrosophia included medical cures and drugs, but also spells, exorcisms, magic,
      astrology, and practical advice. The writer of our oneirokrites used such a
      magico-medical iatrosophion. After interpreting a dream symbol, he often advises
      a prophylactic (usually dietary) cure or treatment for restoring or maintaining
      health, or recommends religious prayers and spells, or apotropaic magic.

PMID- 20695397
TI  - [Dreams in ancient Hebrew sources].
AB  - As in many cultures dreams are, in Hebrew sources, the object of numerous
      questions where are dreams from? Which is their function? Are they a physical or
      metaphysical phenomenon? The article analyzes the topic of nature of dreams in
      the Bible, with a particolar attention devoted to the Joseph's history. Talmudic
      text are, in particular, rich in references.

PMID- 20695398
TI  - [Tertullianus and Agostinus. Approaches to dreams in ancient Christianity].
AB  - The author analyzes the nature and typologies of dreams in Tertullianus' De anima
      and, briefly, in the work of Agostinus, two centuries later. What are made dreams
      of? Are they autonomous productions of psyche or phantasia, or rather messages
      sent by demons or God, according to dreams' bad or good intimate nature? Is there
      a relation between time of the night and nature of the dreams? Moreover, is there
      a relation between seasons and dreams? Does a specific relationship between food,
      regimen and dreams exist? Which is the soul's faculty able to generate dreams? Is
      phantasia moved by some other deep and mysterious principle? Which are the
      connections linking human physiology and dreams?

PMID- 20695399
TI  - [Dreaming archetypes].
AB  - The Jungian notion of archetype is compared with the one developed by Ernst
      Curtius, also derived from Jung. Both notions are seen against the background of
      modernity--that both authors identify with Nazism--thus highlighting the
      ambiguity and potentiality embedded in Jung's original thought, generally
      neglected in later developments.

PMID- 20695400
TI  - [Mauro Mancia: the dream between psychoanalysis and neurosciences].
AB  - "Dreaming, in any case, remains a mental activity and not a physiological
      process, even though it springs from this process". This sentence of Mauro Mancia
      encapsulates the entire significance of his studies on sleeping/dreaming. A
      totality of observations and reflections grounded in neurophysiology and
      psychoanalysis which led him to study and to "see" the two faces of a problem
      that has engaged man's attention since the remotest antiquity. Mancia has thus
      given us the resources to see the dream-and not only the dream-with the marvelled
      eye of the artist who seeks and finds a sense in things and at the same time with
      the cold eye of the scientist who demands of things only their how and wherefore.

PMID- 20695401
TI  - [The Sante De Sanctis' psychophysiology of dreams].
AB  - Sante De Sanctis (1862-1935), a pioneer of psychology in Rome at the end of the
      19th century, applied methods from the expanding field of experimental psychology
      to the study of dreams, which was considered one of the leading ways to gain an
      understanding of normal and pathological psychic life. The multi-faceted
      methodology that he adopted for the study of an, until then, marginal phenomenon
      of the 'new' psychology, represented an element of originality that also included
      the elaboration of a psychophysiological theory of dreams. Although the Italian
      psychologist's work on dreams was characterized by these important methodological
      changes, it disappeared from the references of those who contributed to the
      foundation of modern dreaming psychology after the Second World War.

PMID- 20695402
TI  - Somnium and visio in the Decameron.
AB  - The article focuses on dreams and visions in Boccaccio's Decameron. Starting with
      medieval dream categorization and interpretation, both classical and popular
      influences are explored, showing how Boccaccio combines them in an original
      perspective, in which the truthfulness of dreams relies on the accuracy of their
      premonitions rather than their factual or historical content. A careful
      assessment of Lisabetta da Messina's novella brings out subtle psychological and
      moral nuances, through a dark but suggestive symbolism, as the main character
      defies authority and 'waters'her lover's severed head with her tears, thus
      generating a figurative offspring in the basilico plant. A comparative analysis
      of Boccaccio's novella on Nastagio degli Onesti and Passavanti's text dwells on
      the importance of supernatural references and highlights a radical subversion of
      moral values. Boccaccio appears to depart from tradition, as he ascribes worth to
      love and abandonment instead of restraint, framing the concept of 'superstition'
      in a new, positive context.

PMID- 20695403
TI  - [Dreams and medicine in the pergamum asklepieion].
AB  - The article discusses the main aspects of the onirical theraphy in Greek
      theurgical medicine, practised, as well known, in Asklepius' temples all over
      Greek territories. Iamata, written sources and chronicles furnish reliable
      testimonies of activities performed in the sacred structures, most of which
      concerning the reading and interpretations of dreams. A privileged witness of
      these practices is Aelius Aristides, in the Ieroi Logoi describing the particular
      link connecting his psychological and metaphorical diseases to the divine power
      of Asklepius, revealing his healing terrific capacities mainly through
      therapeutic dreams.

PMID- 20695404
TI  - [Female erotic dreams and female seed in ancient Greek medicine].
AB  - This paper analyses passages of the Hippocratic Corpus, of Aristotle and Galen
      about oneirogmos, spermatic emission during sleep, referring specifically to
      women. Into the Hippocratic texts there is only one gynaecological case among
      many cases about males: for them this nocturnal emission is symptom of dangerous
      illness and De genitura gives a causal explanation of such phaenomenon. Instead,
      in Aristotle and Galen erotic dream is evidence for or against emission of female
      seed and female contribution to generation. As the argument ofHistoria animalium
      book X shows clear theoretical differences from that of De generatione animalium,
      the topic of erotic dream also concerns issues of authenticity.

PMID- 20695405
TI  - ["Interpreter of dreams" and "dreamer" in Homer].
AB  - In this essay I examine the figure of the homeric [Greek characters: see text], a
      term which recurs in two passages of the Iliad (I 63; V 149). It has been
      explained both with the meaning of "interpreter of dreams" and of "dreamer" using
      his own gifts in favour of the community. This latter seems to be the most
      ancient use of the word, as it results in the episode told in the first book of
      the Iliad (crisis in the Greek army after the plague sent by Apollo). This use
      has an interesting parallel in some functions of the Spartan ephors and, in the
      second millennium, in the professional figure of the "dreamer" in the nearby
      Hittite area. More doubtful is the meaning in the Iliad V 149, since, in this
      case, there are no sufficient reasons to give the commonly attributed meaning of
      "interpreter of dreams". The analysis of the word, which is undoubtedly linked to
      the epic tradition, also offers the occasion to linger on some important homeric
      dreams (Agamemnon, Penelope) and on the use of the same word in the Stories by
      Herodotus.

PMID- 20695406
TI  - [Introduction to a history of dreams in art].
AB  - The article traces a brief history "by images" of the representation of dreams in
      art, from the Greek iamata to engravures, printings and paintings of Early Modern
      Age. Particular attention is devoted to the representation of alchemic processes
      in a printed image by Marcantonio Raimondi.

PMID- 20695407
TI  - [Oniric images as illusory appearances in Greek ancient thought].
AB  - This essay traces the history of 'oniric images' as phantasmata in the Greek
      ancient thought from Homer to Stoicism. The author will follow the indications
      furnished by the concept of 'oniric deceit', i.e., phantasma as illusory
      appearance hiding to the sleeper its own deceitful nature.

PMID- 20695408
TI  - [Modernity in dreams and myths].
AB  - The very presence of myths in psychoanalysis raises questions about their
      scientific status: that leads to reconsider the whole issue of Freudian mythology
      in a non-medical manner, by envisaging it in the more general context of modern
      myths, both political and artistic. Special attention is then paid to Surrealism,
      as the only avant-garde movement at the same time focused on psychoanalysis and
      politics: the role played by dreams in foundering myths is examined in both
      Surrealism and psychoanalysis. Surrealistic myths, such as Dali's Grand
      Paranoiaque Comestible, finally prove to be so non-oedipian as the Nazi
      Ubermensch myth; nevertheless, their comparison with Freudian mythology points
      out their common origin, as they all fulfilled the need of the mass society for a
      modern myth, able to express his deeply renewed self-awareness.

PMID- 20695409
TI  - British prisoners-of-war: from resilience to psychological vulnerability: reality
      or perception.
AB  - In contemporary culture, soldiers held as prisoners-of-war (POWs) or as hostages
      are considered at significant risk of mental illness, in particular post
      traumatic stress disorder (PTSD). This assumption contrasts with the psychiatric
      orthodoxy of the First World War when it was concluded in both Britain and
      Germany that POWs were protected against 'war neurosis'. Although 'barbed wire
      disease' was identified during time of captivity, post-release effects were not
      recognized. The repatriation of 'protected' POWs in 1943 prompted a reassessment
      of the psychological impact of imprisonment when servicemen of previous good
      character began to behave aberrantly. Rehabilitation programmes were designed to
      enable soldiers to re-adapt to service or civilian roles. Difficulties of
      adjustment were cast in social and cognitive terms, and corrective measures were
      occupational and educational. Psychiatric disorders found in POWs were explained
      in terms of a pre-conflict predisposition to, or a history of, mental illness.
      However, retrospective studies of veteran POWs have found a high prevalence of
      PTSD. A change in attitudes is explored in relation to the advance of medical
      terminology into the territory of emotions and the attribution of pathological
      processes to self-recovering mental states. The reclassification of the effects
      of imprisonment implies that diagnoses in military psychiatry are culturally
      determined and can be understood only if they are placed in a context that
      includes changing beliefs about mental illness, the formal development of the
      psychiatric profession and the immediate needs of the armed forces.

PMID- 20695410
TI  - [Temporal layers of the clone. Remarks on a conceptual history].
AB  - This paper aims at a history of the clone concept in 20th-century life science
      and culture. The first part of the paper is concerned with conceptual history
      approaches. Here, the idea of 'Zeitschichten' by Reinhart Koselleck is discussed
      and its implications for the history of science are explored. In the following
      parts of the paper, I trace the historical dynamics of the clone concept in
      various fields of 20th-century life sciences. I argue that the clone concept,
      which originated in plant breeding around 1900, soon developed into a technical
      tool in a variety of research areas. With this, specific meanings became
      attached: the idea of standardization, genetic identity, and mass reproduction. A
      further connotation of the clone was the idea of stagnancy with respect to
      processes in time: The clone was seen as something that was exempt from
      evolutionary changes. In the last section of the paper, I trace the shifting
      meanings of the clone concept in the 1960s and 1970s, when the clone became a
      widespread metaphor that pointed to future biotechnologically driven
      possibilities to reshape the nature of human beings. In this regard, the debates
      of the 1970s are analyzed as a turning point: Whereas utopian and eugenic visions
      predominated the debates in the 1960s (when the human clone was seen as something
      which will occur in a distant future), the 1970s discussion focused on the advent
      of a biotechnological era and the human clone had became a reality.

PMID- 20695411
TI  - [On Georges Canguilhem's "What does a scientific ideology mean?" and on French
      German contributions on science and ideology in the last forty years].
AB  - This paper is based on Canguilhem's text on the concept of scientific ideology,
      which he introduced in 1969. We describe Canguilhem's attempts at designing a
      methodological framework for the history of science including the status of kinds
      of knowledge related to science, like scientific ideologies preceding particular
      scientific domains (like ideologies about inheritance before Mendel, or Spencer's
      universal evolutionary laws preceding Darwin). This attempt at picturing the
      relationships between science and ideology is compared with Jurgen Habermas's
      book Technology and Science as 'Ideology' in 1968. The philosphical issue of
      human normativity provides the framework of this discussion.

PMID- 20695412
TI  - (Re)cognizing postmodernity: helps for historians--of science especially.
AB  - Postmodernity, a historical era demarcated from modernity by a broad reversal in
      cultural presuppositions, is distinguished from postmodernism, an intellectual
      posture adopted by self-identified postmodernists early in postmodernity. Two
      principal features of postmodernity are addressed: first, the downgrading of
      science and the upgrading of technology in cultural rank--on which postmodernity
      and postmodernism are in accord; second, the displacement of the methodical,
      disinterested scientist, modernity's beau ideal, not by a fragmented subject as
      postmodernism claims, but by the single-minded entrepreneur, resourcefully
      pursuing his self-interest in disregard of all rules. The reversal in rank and
      role as between science and technology, setting in circa 1980, is a marker of the
      transition from modernity to postmodernity. That reversal is to be cognized
      primarily as rejection of rule-following, of proceeding methodically--'methodism'
      being the cultural perspective that uniquely distinguished modernity--but also as
      rejection of disinterestedness, the quality of mind especially highly esteemed in
      modernity. Postmodernity is constituted by this transvaluation of values, whose
      well-spring is the egocentric, transgressive (hence 'risk taking'), postmodern
      personality and its anti-social presumptions regarding personhood. Within the
      history of science itself there has been since circa 1980 a corresponding turn of
      scholarly attention away from science to technology, and a growing distaste for
      social perspectives, reflected, i.a., in the rejection of causalist 'influence'
      explanations in favor of voluntarist 'resource' explanations.

PMID- 20695413
TI  - [In search of politics in knowledge production. A plea for a historical-political
      epistemology].
AB  - Knowledge production has an intrinsic political dimension. Starting from this
      presupposition, it is argued that the systematic integration of and reflection on
      the political dimension is necessary for an adequate understanding of historical
      processes of knowledge production in the sciences. The consecutive plea for a
      historical-political epistemology proceeds in two steps: First, it is illustrated
      that in a number of recent historical science study cases, the political
      dimension is frequently marginal, or even absent. After a short discussion of
      previous theoretical concepts to describe the impact of politics for the
      production of scientific knowledge, an approach is sketched which builds on Hans
      Jorg Rheinberger's historical epistemology and Bruno Latour's symmetrical
      anthropology. It is argued that in addition to Rheinberger's program to describe
      epistemic systems, the political dimension is intrinsic to three stages of the
      process of data production: First to an initial phase which consists in the
      arrangement socio-technical configurations to produce new evidence. Here, factors
      such as the culturally shaped perception and evaluation of "relevant" problems,
      as well as the perception of career resources have to be taken into account.
      Second, the political dimension is relevant in view of the continuous re
      adjustments of the configuration of epistemic systems, e.g., towards newly
      available financial, technical, or intellectual resources and "relevant"
      challenges from outside the system. Thirdly, the data produced and represented by
      epistemic systems--"evidence"--are yet in need of interpretation. This process is
      in itself imbued with continuously shifting mechanisms of selecting and creating
      hierarchies amongst the pool of available data.

PMID- 20695414
TI  - [A political matter: science and ideology in the 21st century].
AB  - In the last two decades, history of science and science studies have been quite
      reluctant to adopt the notion of ideology when analyzing the dynamics of science.
      This may be an effect of the decreasing popularity of neo-marxist approaches
      within this disciplinary field; but it is also due to the fact that alternative
      approaches have been developed, for example Michel Foucault's notion of
      problematization, Roland Barthes' semiotic mythology, Bruno Latour's re
      interpretation of the ontological difference between fact and fetish in science,
      or Donna Haraway's semi-fictional re-narrations of the techno-scientific world.
      This contribution undertakes to sketch the impact of two strands of 19th century
      immanentism on the authors named above, and on their use of concepts related to
      the notion of ideology, namely fetish, fetishism, myth and mythology
      respectively. It is argued that in some respect, Marx' concept of commodity
      fetishism is worth being re-examined, since it articulates a dialectical relation
      of 'reality' and 'seeming', and its impact on Barthes' mythology is deeper than
      it might appear at first glance.

PMID- 20695415
TI  - Instrumental images: the visual rhetoric of self-presentation in Hevelius's
      Machina Coelestis.
AB  - This article places the famous images of Johannes Hevelius's instruments in his
      Machina Coelestis (1673) in the context of Hevelius's contested cometary
      observations and his debate with Hooke over telescopic sights. Seen thus, the
      images promote a crafted vision of Hevelius's astronomical practice and skills,
      constituting a careful self-presentation to his distant professional network and
      a claim as to which instrumental techniques guarantee accurate observations.
      Reviewing the reception of the images, the article explores how visual rhetoric
      may be invoked and challenged in the context of controversy, and suggests renewed
      analytical attention to the role of laboratory imagery in instrumental cultures
      in the history of science.

PMID- 20695416
TI  - 2009 employment decisions under the ADA Title I--survey update.

PMID- 20695417
TI  - Patriarchal families and national wars.

PMID- 20695418
TI  - The unreality principle and deregulation: a psychocultural exploration.

PMID- 20695419
TI  - Dwight D. Eisenhower: The call of duty and the love of applause.

PMID- 20695420
TI  - Saving boys from the church: a thematic survey and a personal odyssey.

PMID- 20695421
TI  - [Does not know of time but marks destiny].

PMID- 20695422
TI  - Rapid and simultaneous determination of essential minerals and trace elements in
      human milk by improved flame atomic absorption spectroscopy (FAAS) with microwave
      digestion.
AB  - A method for the simultaneous and economical determination of many trace elements
      in human milk is developed. Two multi-element hollow cathode lamps (HCLs) were
      used instead of single-element HCLs to improve the sample throughput of flame
      atomic absorption spectroscopy (FAAS). The microwave digestion of milk is
      optimized prior to detection, and the performance characteristics of the improved
      analysis method are identified. Clinical samples are detected by both FAAS and
      inductively coupled plasma-optical emission spectroscopy (ICP-OES) for
      methodology evaluation. Results reveal that the proposed FAAS with multi-element
      HCLs could determine six essential minerals and trace elements within 15 min.
      This method provides a linear analytical range of 0.01-10 mg L(-1). For Ca, Cu,
      Fe, Mg, Mn, and Zn, the limits of determination are 1.5, 3, 1.8, 2.2, 2.1, and
      1.3 microg L(-1), respectively. The mean relative standard deviations (RSDs) of
      intra- and interassays are lower than 7%. Excellent operational characteristics
      of rapidity, simplicity, and economy make the proposed method a promising one for
      the quantification of trace elements in human milk in clinics of underdeveloped
      areas.

PMID- 20695424
TI  - Analysis of carotenoids in grapes to predict norisoprenoid varietal aroma of
      wines from Apulia.
AB  - To determine a correlation between carotenoid precursors in grapes and
      norisoprenoid varietal aroma of wine, carotenoids were identified and quantified
      by HPLC-DAD-MS (ESI+) from four representative wine grape varieties of the
      Apulian region (Chardonnay, Merlot, Negroamaro, Primitivo) in two years of study
      (2006-2007), and C13-norisoprenoid aroma potential, DeltaC (microg/kg), was
      calculated from the difference of total carotenoid concentration between veraison
      and maturity. C13-norisoprenoids were analyzed by GC-MS in the obtained wines
      from 2006 and 2007 vintages. Higher DeltaC values, found in Chardonnay and Merlot
      grapes, corresponded to higher norisoprenoid contents in the respective wines,
      particularly characterized by highly flavorant compounds such as beta-damascenone
      and 3-oxo-alpha-ionol. A linear regression was determined that was significant at
      the 0.01% level (F=36.12, p=0.00096) with R=0.9261, between grape DeltaC values
      and total norisoprenoid contents in wine. These findings support the hypothesis
      that DeltaC could be a useful technological tool to predict norisoprenoid aroma
      of wine and, consequently, to identify grapes with higher aroma potential.

PMID- 20695423
TI  - Effects of PEGylation and acetylation of PAMAM dendrimers on DNA binding,
      cytotoxicity and in vitro transfection efficiency.
AB  - Poly(amidoamine) (PAMAM) dendrimers are promising multipotent gene delivery
      vectors, providing favorable DNA condensation properties also in combination with
      the possibility of conjugation of different targeting ligands to their surface.
      They have been used for transfection both in vitro and in vivo, but their
      application is currently somewhat limited due to inherent cytotoxicity. In this
      work we investigate how two types of surface modification, acetylation and
      PEGylation, affect the DNA binding characteristics, the cytotoxicity and the in
      vitro transfection efficiency of generation 4 and 5 PAMAM dendrimers.
      Particularly, we address how the morphology of DNA-dendrimer complexes, formed
      under low salt conditions, changes upon dilution in cell growth medium, an event
      that inevitably occurs before the complexes reach the cell surface in any
      transfection experiment. We find that acetylation and PEGylation essentially
      eliminates the inherent dendrimer cytotoxicity. However, the transfection
      efficiency of the modified dendrimers is lower than that of the corresponding
      unmodified dendrimers, which can be rationally understood by our observations
      that DNA is less condensed when complexed with these modified dendrimers.
      Although small DNA-dendrimer particles are formed, the availability for ethidium
      intercalation and nuclease degradation is significantly higher in the modified
      DNA-dendrimer complexes than in unmodified ones. Dilution in cell growth medium
      has a drastic effect on these electrostatically assembled complexes, resulting in
      increase in size and DNA availability. Our results strongly add to the notion
      that it is of importance to perform a biophysical characterization under
      conditions as close to the transfection situation as possible, to enable
      conclusions regarding structure-activity relations of gene delivery vectors.

PMID- 20695425
TI  - Ewe's diet (pasture vs grain-based feed) affects volatile profile of cooked meat
      from light lamb.
AB  - The effects of ewe's diet during gestation and lactation on the volatile
      compounds profile in cooked meat from light lamb were compared. Two lamb groups
      from ewes that had been fed pasture (PA) or grain-based concentrate (FE) were
      tested. Cooked loin mixed with saliva was analyzed by solid phase
      microextraction, gas chromatography, and mass spectrometry. The fiber coating
      used was divinylbenzene-carboxen-polydimethylsiloxane. The volatiles detected and
      quantified were aldehydes, alcohols, ketones, phenols, indole, and sulfur
      compounds. The ewe's diet strongly affected the volatile compounds profile of the
      cooked meat. The total volatiles concentration was higher in PA (409 mg kg(-1))
      than in FE (201 mg kg(-1)). The major volatiles in PA were phenol, 4
      methylphenol, and hexanoic acid, while the major volatile in FE was 3-hydroxy-2
      butanone. No branched C8-C9 fatty acids responsible for mutton flavor were
      detected in either group. The findings suggest that nutritional strategies can be
      use during gestation and lactation to modify the aroma of light lamb meat in the
      light of consumer preferences.

PMID- 20695426
TI  - Dynamic changes in gamma-aminobutyric acid and glutamate decarboxylase activity
      in oats (Avena nuda L.) during steeping and germination.
AB  - Gamma-aminobutyric acid (GABA) is the principal inhibitory neurotransmitter in
      the central nervous system and provides beneficial effects for human and other
      animals health. To accumulate GABA, samples from two different naked oat
      cultivars, Baiyan II and Bayou I, were steeped and germinated in an incubator.
      The content of GABA and glutamic acid as well as the activity of the glutamate
      decarboxylase (GAD) in oats during steeping and germination were investigated
      with an amino acid automatic analyzer. Compared with raw groats, an increase in
      GABA content of oat groats during steeping and germination was continuously
      observed for two oat cultivars. The activity of GAD increased greatly at the end
      of steeping and the second stage of germination for Baiyan II and Bayou I,
      respectively. Glutamic acid content of treated oat groats was significantly lower
      than that in raw groats until the later period of germination. GABA was
      correlated (p<0.01) significantly and positively with the glutamic acid rather
      than GAD activity in the current study. The results indicates that steeping and
      germination process under highly controlled conditions can effectively accumulate
      the GABA in oat groats for Baiyan II and Bayou I, which would greatly facilitate
      production of nutraceuticals or food ingredients that enable consumers to gain
      greater access to the health benefits of oats. However, more assays need to be
      further performed with more oat cultivars.

PMID- 20695428
TI  - Dioxin formations from the radical/radical cross-condensation of phenoxy radicals
      with 2-chlorophenoxy radicals and 2,4,6-trichlorophenoxy radicals.
AB  - It is important to understand the role of phenol in the dioxin formations because
      it is present in the high amount in municipal waste incinerators (MWIs). The
      formation mechanism of dioxins from the cross-condensation of PhRs with 2-CPRs
      and 2,4,6-TCPRs was investigated by using hybrid density functional theory (DFT)
      and compared with the dioxin formation mechanism from the self-condensation of
      single chlorophenol precursors. The geometrical parameters were optimized at the
      MPWB1K level with the 6-31+G(d,p) basis set without symmetry constraints. Single
      point energy calculations were carried out at the MPWB1K/6-311+G(3df,2p) level of
      theory. The rate constants were deduced by using canonical variational transition
      state (CVT) theory with small curvature tunneling (SCT) contribution over the
      temperature range of 600-1200 K. The Arrhenius formulas were reported for the
      first time. Results show that phenol is responsible for the formation of dioxin
      congeners. This work, together with results already published from our group,
      provides a comprehensive investigation of the homogeneous gas-phase formation of
      dioxins from (chloro)phenol precursors and should help to clarify the formation
      mechanism of dioxins in real waste combustion and to develop more effective
      control strategies.

PMID- 20695427
TI  - Structural and functional basis of resistance to neuraminidase inhibitors of
      influenza B viruses.
AB  - We have identified a virus, B/Perth/211/2001, with a spontaneous mutation, D197E
      in the neuraminidase (NA), which confers cross-resistance to all NA inhibitors.
      We analyzed enzyme properties of the D197 and E197 NAs and compared these to a
      D197N NA, known to arise after oseltamivir treatment. Zanamivir and peramivir
      bound slowly to the wild type NA, but binding of oseltamivir was more rapid. The
      D197E/N mutations resulted in faster binding of all three inhibitors. Analysis of
      the crystal structures of D197 and E197 NAs with and without inhibitors showed
      that the D197E mutation compromised the interaction of neighboring R150 with the
      N-acetyl group, common to the substrate sialic acid and all NA inhibitors.
      Although rotation of the E275 in the NA active site occurs upon binding peramivir
      in both the D197 and E197 NAs, this does not occur upon binding oseltamivir in
      the E197 NA. Lack of the E275 rotation would also account for the loss of slow
      binding and the partial resistance of influenza B wild type NAs to oseltamivir.

PMID- 20695429
TI  - New class of algicidal compounds and fungicidal activities derived from a
      chromene amide of Amyris texana.
AB  - A chromene amide, N-[2-(2,2-dimethyl-2H-1-benzopyran-6-yl)ethyl]-N,3
      dimethylbutanamide, was isolated from the EtOAc extract of the leaves of Amyris
      texana and found to have moderate antifungal activity against Colletotrichum spp.
      and selective algicidal activity against Planktothrix perornata, a cyanobacterium
      (blue-green alga) that causes musty off-flavor in farm-raised channel catfish
      (Ictalurus punctatus). To improve the selective algicidal activity and provide
      water solubility, a series of chromene analogues were synthesized and evaluated
      for algicidal activity using a 96-well microplate rapid bioassay. In addition,
      the chromene analogues were evaluated for antifungal and phytotoxic activities.
      Hydrochloride salts of a chromene amine analogue showed improved water solubility
      and selectivity toward P. perornata with activity comparable to that of the
      naturally occurring chromene amide.

PMID- 20695430
TI  - Sulfur-based redox reactions in Mo3S7(4+) and Mo3S4(4+) clusters bearing halide
      and 1,2-dithiolene ligands: a mass spectrometric and density functional theory
      study.
AB  - The gas phase fragmentation reactions of sulfur-rich [Mo(3)S(7)Br(6)](2-) (1(2
      )), [Mo(3)S(7)(bdt)(3)](2-) (2(2-)), and [Mo(3)S(4)(bdt)(3)](2-) (3(2-)) (bdt =
      benzenedithiolate) complexes have been investigated by electrospray ionization
      (ESI) tandem mass spectrometry and theoretical calculations at the density
      functional theory level. Upon collision induced dissociation (CID) conditions,
      the brominated 1(2-) dianion dissociates through two sequential steps that
      involves a heterolytic Mo-Br cleavage to give [Mo(3)S(7)Br(5)](-) plus Br(-)
      followed by a two-electron redox process that affords [Mo(3)S(5)Br(5)](-) and
      diatomic S(2) sulfur. Dianion [Mo(3)S(7)(bdt)(3)](2-) (2(2-)) dissociates through
      two sequential redox processes evolving diatomic S(2) sulfur and neutral bdt to
      yield [Mo(3)S(5)(bdt)(3)](2-) and [Mo(3)S(5)(bdt)(2)](2-), respectively.
      Conversely, dianion [Mo(3)S(4)(bdt)(3)](2-) (3(2-)), with sulfide instead of
      disulfide S(2)(2-) bridged ligands, remains intact under identical fragmentation
      conditions, thus highlighting the importance of disulfide ligands (S(2)(2-)) as
      electron reservoirs to trigger redox reactions. Regioselective incorporation of
      (34)S and Se at the equatorial position of the Mo(3)S(7) cluster core in 1(2-)
      and 2(2-) have been used to identify the product ions along the fragmentation
      pathways. Reaction mechanisms for the gas-phase dissociation pathways have been
      elucidated by means of B3LYP calculations, and a comparison with the solution
      reactivity of Mo(3)S(7) and Mo(3)S(4) clusters as well as closely related
      Mo/S/dithiolene systems is also discussed.

PMID- 20695431
TI  - Comparison of hydrazone heterobifunctional cross-linking agents for reversible
      conjugation of thiol-containing chemistry.
AB  - Reversible covalent conjugation chemistries that allow site- and condition
      specific coupling and uncoupling reactions are attractive components in
      nanotechnologies, bioconjugation methods, imaging, and drug delivery systems.
      Here, we compare three heterobifunctional cross-linkers, containing both thiol-
      and amine-reactive chemistries, to form pH-labile hydrazones with hydrazide
      derivatives of the known and often published water-soluble polymer, poly[N-(2
      hydroxypropyl methacrylamide)] (pHPMA), while subsequently coupling thiol
      containing molecules to the cross-linker via maleimide addition. Two novel cross
      linkers were prepared from the popular heterobifunctional cross-linking agent,
      succinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate (SMCC), modified to
      contain either terminal aldehyde groups (i.e., 1-(N-3-propanal)-4-(N
      maleimidomethyl) cyclohexane carboxamide, PMCA) or methylketone groups (i.e., 1
      (N-3-butanone)-4-(N-maleimidomethyl) cyclohexane carboxamide, BMCA). A third
      cross-linking agent was the commercially available N-4-acetylphenyl maleimide
      (APM). PMCA and BMCA exhibited excellent reactivity toward hydrazide-derivatized
      pHPMA with essentially complete hydrazone conjugation to polymer reactive sites,
      while APM coupled only ~60% of available reactive sites on the polymer despite a
      3-fold molar excess relative to polymer hydrazide groups. All polymer hydrazone
      conjugates bearing these bifunctional agents were then further reacted with thiol
      modified tetramethylrhodamine dye, confirming cross-linker maleimide reactivity
      after initial hydrazone polymer conjugation. Incubation of dye-labeled polymer
      conjugates in phosphate buffered saline at 37  degrees C showed that hydrazone
      coupling resulting from APM exhibited the greatest difference in stability
      between pH 7.4 and 5.0, with hydrolysis and dye release increased at pH 5.0 over
      a 24 h incubation period. Polymer conjugates bearing hydrazones formed from cross
      linker BMCA exhibited intermediate stability with hydrolysis much greater at pH
      5.0 at early time points, but hydrolysis at pH 7.4 was significant after 5 h.
      Hydrazones formed with the PMCA cross-linker showed no difference in release
      rates at pH 7.4 and 5.0.

PMID- 20695432
TI  - Efficient gene transfection using novel cationic polymers poly(hydroxyalkylene
      imines).
AB  - A series of novel cationic polymers poly(hydroxyalkylene imines) were synthesized
      and tested for their ability to transfect cells in vitro and in vivo.
      Poly(hydroxyalkylene imines), in particular, poly(2-hydroxypropylene imine)
      (pHP), poly(2-hydroxypropylene imine ethylene imine) (pHPE), and
      poly(hydroxypropylene imine propylene imine) (pHPP) were synthesized by
      polycondensation reaction from 1,3-diamino-2-propanol and the appropriate
      dibromide. Electron microscopic examination demonstrated that the resulting
      polymers condensed DNA into toroid shape complexes of 100-150 nm in size.
      Transfection studies showed that all three polymers were able to deliver genetic
      material into the cell, with pHP being superior to pHPP and pHPE. pHP acted as an
      efficient gene delivery agent in a variety of different cell lines and
      outcompeted most of the widely used polymer or lipid based transfection reagents.
      Intravenous administration of pHP-DNA polyplexes in mice followed by the reporter
      gene analysis showed that the reagent was suitable for in vivo applications. In
      summary, the results indicate that pHP is a new efficient reagent for gene
      delivery in vitro and in vivo.

PMID- 20695433
TI  - Band gap and composition engineering on a nanocrystal (BCEN) in solution.
AB  - Colloidal nanocrystals with "artificial" composition and electron band structure
      promise to expand the fields of nanomaterials and inorganic chemistry. Despite
      their promise as functional materials, the fundamental science associated with
      the synthesis, characterization, and properties of colloidal nanocrystals is
      still in its infancy and deserves systematic study. Furthermore, such studies are
      important for our basic understanding of crystallization, surface science, and
      solid state chemistry. "Band gap and composition engineering on a nanocrystal"
      (BCEN) refers to the synthesis of a colloidal nanocrystal with composition and/or
      electron energy band structure that are not found in natural bulk crystals. The
      BCEN nanostructure shown in the Figure includes a magnetic domain for the
      separation and recycling of the complex nanostructure, a photoactivated catalytic
      center, and an additional chemical catalytic center. A thin but porous film (such
      as a silicate) might be coated onto the nanocrystal, both to provide chemical
      stability and to isolate the reaction processes from the bulk solution. This
      example is a catalytic complex analogous to an enzyme that facilitates two
      sequential reactions in a microenvironment different from bulk solution. The
      synthesis of colloidal nanocrystals has advanced by a quantum leap in the past
      two decades. The field now seems ready to extend colloidal nanocrystal synthesis
      into the BCEN regime. Although BCEN is a very new branch of synthetic chemistry,
      this Account describes advances in related synthetic and characterization
      techniques that can serve as a useful starting point for this new area of
      investigation. To put these ideas into context, this Account compares this new
      field with organic synthesis, the most developed branch in synthetic chemistry.
      The structural and functional diversity of organic compounds results from
      extending design and synthesis beyond the construction of natural organic
      compounds. If this idea also holds true for inorganic nanocrystals, "artificial"
      BCEN nanocrystals will most likely outperform the inorganic nanocrystals with
      naturally occurring structure and composition. If the importance of artificial
      molecules is a positive lesson from organic synthesis, the practical disadvantage
      of organic chemistry is that purification can prove much more time consuming than
      the reaction itself. To get around this problem, colloidal nanocrystal chemists
      can attempt to avoid these potential purification challenges in the early stages
      of synthetic method development.

PMID- 20695435
TI  - Atmospheric pressure-ion drift chemical ionization mass spectrometry for
      detection of trace gas species.
AB  - This paper describes atmospheric pressure-ion drift chemical ionization mass
      spectrometry (AP-ID-CIMS) for monitoring of ambient trace species. Operation of
      the drift tube at atmospheric pressure allows a significantly longer ion-molecule
      reaction time and eliminates dilution of the ambient samples, while a well
      defined electric field inside the drift tube provides the benefits to confine the
      flight path and velocity of reagent/product ions, to break down ion clusters, and
      to control the ion-molecule reaction time. The AP-ID-CIMS exhibits advantages
      over the conventional low pressure ID-CIMS and flow tube AP-CIMS, improving the
      detection sensitivity by 3 orders of magnitude and a factor of 3, respectively.
      We demonstrate that the AP-ID-CIMS allows quantification of sulfuric acid
      concentrations and is capable of detecting gaseous sulfuric acid with a detection
      limit of less than 10(5) molecules cm(-3), on the basis of 3sigma of the baseline
      noise and an integration time of 12 s. A field evaluation of the AP-ID-CIMS is
      presented for ambient H(2)SO(4) measurements.

PMID- 20695434
TI  - Silver-catalyzed late-stage fluorination.
AB  - Carbon-fluorine bond formation by transition metal catalysis is difficult, and
      only a few methods for the synthesis of aryl fluorides have been developed. All
      reported transition-metal-catalyzed fluorination reactions for the synthesis of
      functionalized arenes are based on palladium. Here we present silver catalysis
      for carbon-fluorine bond formation. Our report is the first example of the use of
      the transition metal silver to form carbon-heteroatom bonds by cross-coupling
      catalysis. The functional group tolerance and substrate scope presented here have
      not been demonstrated for any other fluorination reaction to date.

PMID- 20695436
TI  - CdSe/ZnS quantum dots-G-quadruplex/hemin hybrids as optical DNA sensors and
      aptasensors.
AB  - The luminescence of CdSe/ZnS QDs is quenched via electron transfer by hemin/G
      quadruplex associated with the particles. This phenomenon is implemented to
      develop DNA sensors or aptasensors by tailoring hairpin-functionalized QDs that
      generate the hemin/G-quadruplex quenchers upon sensing of the respective
      analytes.

PMID- 20695437
TI  - Theoretical prediction of stable noble-gas anions XeNO(2)(-) and XeNO(3)(-) with
      very short xenon-nitrogen bond lengths.
AB  - We have predicted a new type of noble-gas anions, XeNO(2)(-) and XeNO(3)(-) with
      very short Xe-N bond lengths ( approximately 1.8 A), using high-level electronic
      structure theory with extended atomic basis sets. The chemical bonding between
      xenon and nitrogen atoms could formally be assigned as triple bonds. The best
      estimates of the atomization energies of the two anions were found to be 50 and
      101 kcal/mol, respectively, and the lowest unimolecular dissociation barriers
      were estimated to be approximately 42 kcal/mol. These anions were predicted to be
      kinetically stable at low temperature. The possible neutral "salts" formed
      between the lithium cation and these two anions were also discussed.

PMID- 20695438
TI  - Design and synthesis of a long-wavelength latent fluorogenic substrate for
      salicylate hydroxylase: a useful fluorimetric indicator for analyte determination
      by dehydrogenase-coupled biosensors.
AB  - Salicylate hydroxylase (SHL) catalyzes the production of catechol (plus CO(2) and
      H(2)O) from salicylate, NADH, and O(2). Coimmobilization of SHL with a NAD(P)(+)
      dependent dehydrogenase in front of a Clark-type oxygen electrode has been
      investigated in the development of a general type of dehydrogenase-based
      biosensors that can detect various biological analytes; however, currently, no
      fluorophores are available for these applications. We synthesized the first new
      long-wavelength latent fluorogenic substrate SHLF (3) for SHL. In the presence of
      NADH and under aerobic conditions, SHL catalyzes the decarboxylative
      hydroxylation of SHLF followed by a quinone-methide-type rearrangement reaction
      concomitant with the ejection of a fluorescence coumarin 2, which is spontaneous
      and irreversible at physiological temperatures in aqueous media. The fluorescence
      signal generated by this process is specific and, in the near red spectral region
      with an emission maximum at 595 nm, is suppressed by salicylic acid. The
      fluorescence response of SHLF is insensitive to various biological reactive
      oxygen species (ROS) and reductants. Furthermore, SHLF is a sensitive
      fluorimetric indicator for analyte determination in the SHL-coupled dehydrogenase
      assay in which NAD(+) is converted to NADH. This novel fluorescence assay
      detected 3-hydroxybutyrate and cholesterol in the nanomolar range and is more
      sensitive than the current SHL-dehydrogenase amperometric sensors, making it
      applicable to the construction of a fiber-optic fluorescence biosensor for
      clinical diagnostic uses.

PMID- 20695439
TI  - Coupling desorption electrospray ionization with solid-phase microextraction for
      screening and quantitative analysis of drugs in urine.
AB  - Direct analysis of silica C(18)-coated solid-phase microextraction (SPME) fibers
      using desorption electrospray ionization mass spectrometry (DESI-MS) for the
      purpose of analyzing drugs from raw urine is presented. The method combines a
      simple, inexpensive, and solvent-less sample preparation technique with the
      specificity and speed of DESI-MS and MS/MS. Extraction of seven drugs from raw
      urine is performed using specially designed SPME fibers coated uniformly with
      silica-C(18) stationary phase. Each SPME device is inserted into unprocessed
      urine under gentle agitation and, then, removed, rinsed, and analyzed directly by
      DESI-MS (MS/MS). Rapid screening over a wide mass range is afforded by coupling
      the method with a time of flight (TOF) mass spectrometer while quantitative
      analysis is performed using selected reaction monitoring (SRM) using a triple
      quadrupole mass spectrometer. The performance of the SPME DESI-MS/MS method was
      evaluated by preparing calibration standards and quality control (QC) samples of
      the seven drug compounds from urine over a range from 20 to 1000 ng/mL, with the
      exception of meprobamate which was prepared from 200 to 10000 ng/mL. The
      calibration curves constructed for each analyte had an R(2) > 0.99. The range of
      precision (%CV) and accuracy values (% bias) for low QC samples was 1-11% and 3
      38%, respectively. Precision and accuracy values for high QC samples range from
      0.9 to 8% and -31 to -8%. Results from urine specimens of actual exposure to
      drugs screened using the SPME DESI-MS/MS method showed good agreement with the
      conventional immunoassays and GC/MS analysis. Liquid desorption of the SPME fiber
      followed by LC/MS/MS also showed good agreement with the SPME DESI-MS/MS method.

PMID- 20695440
TI  - Monitoring the uptake and redistribution of metal nanoparticles during cell
      culture using surface-enhanced Raman scattering spectroscopy.
AB  - We describe the uptake of silver nanoparticles by CHO (Chinese hamster ovary)
      cells and their subsequent fate as a result of cell division during culture, as
      monitored by surface-enhanced Raman scattering (SERS) spectroscopy. Mapping of
      populations of cells containing both labeled and native nanoparticles by SERS
      spectroscopy imaging provided a quantitative method by which the number of
      intracellular nanoparticles could be monitored. Initially, for a given amount of
      nanoparticles, the relationship between the number taken up into the cell and the
      time of incubation was explored. Subsequently, the redistribution of
      intracellular nanoparticles upon multiple rounds of cell division was
      investigated. Intracellular SERS signatures remained detectable in the cells for
      up to four generations, although the abundance and intensity of the signals
      declined rapidly as nanoparticles were shared with daughter cells. The intensity
      of the SERS signal was dependent both on stability of the label and their
      abundance (nanoparticle aggregation increases the extent of the SERS
      enhancement). The data show that while the labeled nanoparticles remain stable
      for prolonged periods, during cell division, the changes in signal could be
      attributed both to a decrease in abundance and distribution (and hence
      aggregation).

PMID- 20695441
TI  - New diffusive gradients in a thin film technique for measuring inorganic arsenic
      and selenium(IV) using a titanium dioxide based adsorbent.
AB  - A new diffusive gradients in a thin film (DGT) technique, using a titanium
      dioxide based adsorbent (Metsorb), has been developed and evaluated for the
      determination of dissolved inorganic arsenic and selenium. As(III), As(V), and
      Se(IV) were found to be quantitatively accumulated by the adsorbent (uptake
      efficiencies of 96.5-100%) and eluted in 1 M NaOH (elution efficiencies of 81.2%,
      75.2%, and 88.7%). Se(VI) was not quantitatively accumulated by the adsorbent
      (<20%). Laboratory DGT validation experiments gave linear mass uptake over time
      (R(2) >or= 0.998) for As(III), As(V), and Se(IV). Consistent uptake occurred over
      pH (3.5-8.5) and ionic strength (0.0001-0.75 mol L(-1) NaNO(3)) ranges typical of
      natural waters, including seawater. Field deployments of DGT probes with various
      diffusive layer thicknesses confirmed the use of the technique in situ, allowing
      calculation of the diffusive boundary layers and an accurate measurement of
      inorganic arsenic. Reproducibility of the technique in field deployments was good
      (relative standard deviation <8%). Limits of detection (4 day deployments) were
      0.01 microg L(-1) for inorganic arsenic and 0.05 microg L(-1) for Se(IV). The
      results of this study confirmed that DGT with Metsorb was a reliable and robust
      method for the measurement of inorganic arsenic and the selective measurement of
      Se(IV) within useful limits of accuracy.

PMID- 20695442
TI  - A facile template-free approach to magnetodriven, multifunctional artificial
      cilia.
AB  - Flexible and magnetic artificial cilia were grown on various substrates by a
      facile bottom-up approach based on template-free magnetic assembly. The magnetic
      cilia formed spontaneously from a suspension of micrometer-sized ferromagnetic
      particles and elastomeric polymer in a liquid solvent when dried in an external
      magnetic field. The cilia mimics were mechanically stable even in the absence of
      an external magnetic field and a solvent due to the polymer, which acted as
      "glue" holding the particles together and connecting the cilia to the substrate.
      The length of the magnetic cilia was in the millimeter range, that is, two to
      three orders of magnitude times the length of typical biological cilia. The
      aspect ratio reached values over 100 and was tunable with the magnetic field
      gradient and the size of the ferromagnetic particles. The cilia mimics responded
      to an external magnetic field by reversibly bending along the field. The bending
      actuation was sufficiently powerful to allow two functions: to translate
      macroscopic nonmagnetic objects placed over the cilia mimics and to mix liquids
      of even high viscosity. The mechanical properties of the magnetic cilia could be
      easily tuned by changing the impregnating polymer. The particularly simple
      template-free construction and fixation on various surfaces suggest applications
      as an externally controllable surface.

PMID- 20695446
TI  - Multimode Fabry-Perot conductance oscillations in suspended stacking-faults-free
      InAs nanowires.
AB  - We report on observation of coherent electron transport in suspended high-quality
      InAs nanowire-based devices. The InAs nanowires were grown by low-temperature
      gold-assisted vapor-liquid-solid molecular-beam-epitaxy. The high quality of the
      nanowires was achieved by removing the typically found stacking faults and
      reducing possibility of Au incorporation. Minimizing substrate-induced scattering
      in the device was achieved by suspending the nanowires over predefined grooves.
      Coherent transport involving more than a single one-dimensional mode transport
      was observed in the experiment and manifested by Fabry-Perot conductance
      oscillations. The length of the Fabry-Perot interferometer, deduced from the
      period of the conductance oscillations, was found to be close to the physical
      length of the device. The high oscillations visibility imply nearly ballistic
      electron transport through the nanowire.

PMID- 20695444
TI  - Tuning electronic and magnetic properties of wurtzite ZnO nanosheets by surface
      hydrogenation.
AB  - Through density functional theory computations, we systematically investigated
      the structural, electronic, and magnetic properties as well as the relative
      stabilities of fully and partially hydrogenated ZnO nanosheets. Unlike bare ZnO
      nanosheets terminating with polar {0001} surfaces, their hydrogenated
      counterparts preserve the initial wurtzite configuration. Full hydrogenation is
      more favorable energetically for thinner ZnO nanosheets, whereas
      semihydrogenation at O sites is preferred for thicker ones. Moreover,
      semiconductor --> half-metal --> metal transition occurs with nonmagnetic -->
      magnetic transfer upon adopting surface hydrogenation and increasing sheet
      thickness. The predicted diverse and tunable electronic and magnetic properties
      endow ZnO nanosheets potential applications in electronics and spintronics.

PMID- 20695447
TI  - Tunable band gap in hydrogenated quasi-free-standing graphene.
AB  - We show by angle-resolved photoemission spectroscopy that a tunable gap in quasi
      free-standing monolayer graphene on Au can be induced by hydrogenation. The size
      of the gap can be controlled via hydrogen loading and reaches approximately 1.0
      eV for a hydrogen coverage of 8%. The local rehybridization from sp(2) to sp(3)
      in the chemical bonding is observed by X-ray photoelectron spectroscopy and X-ray
      absorption and allows for a determination of the amount of chemisorbed hydrogen.
      The hydrogen induced gap formation is completely reversible by annealing without
      damaging the graphene. Calculations of the hydrogen loading dependent core level
      binding energies and the spectral function of graphene are in excellent agreement
      with photoemission experiments. Hydrogenation of graphene gives access to tunable
      electronic and optical properties and thereby provides a model system to study
      hydrogen storage in carbon materials.

PMID- 20695448
TI  - Free-radical addition to ketimines generated in situ. New one-pot synthesis of
      quaternary alpha-aminoamides promoted by a H2O2/TiCl4-Zn/HCONH2 system.
AB  - A free radical multicomponent reaction mediated by an acidic TiCl(4)-Zn/H(2)O(2)
      system allows the assembly of an amine, a ketone, and formamide in one pot,
      affording instant access to quaternary alpha-amino acid derivatives.

PMID- 20695449
TI  - Functionalization of aromatic amino acids via direct C-H activation: generation
      of versatile building blocks for accessing novel peptide space.
AB  - Functionalized alpha-amino acid building blocks have been prepared in good yield
      with high regiocontrol and preservation of stereochemistry via iridium-catalyzed
      borylation of suitably protected aromatic alpha-amino acid derivatives. The
      utility of these systems in peptide couplings and Suzuki reactions has been
      demonstrated.

PMID- 20695450
TI  - Stretchable graphene: a close look at fundamental parameters through biaxial
      straining.
AB  - Tunable biaxial stresses, both tensile and compressive, are applied to a single
      layer graphene by utilizing piezoelectric actuators. The Gruneisen parameters for
      the phonons responsible for the D, G, 2D and 2D' peaks are studied. The results
      show that the D peak is composed of two peaks, unambiguously revealing that the
      2D peak frequency (omega(2D)) is not exactly twice that of the D peak (omega(D)).
      This finding is confirmed by varying the biaxial strain of the graphene, from
      which we observe that the shift of omega(2D)/2 and omega(D) are different. The
      employed technique allows a detailed study of the interplay between the graphene
      geometrical structures and its electronic properties.

PMID- 20695452
TI  - Ruthenium-catalyzed aromatic C-H activation of benzylic alcohols via remote
      electronic activation.
AB  - Remote electronic activation of benzylic alcohols via temporary oxidation
      facilitates ruthenium-catalyzed arene C-H activation for a range of aromatic
      alcohols.

PMID- 20695451
TI  - NMR metabolomic profiling reveals new roles of SUMOylation in DNA damage
      response.
AB  - Post-translational modifications by the Small Ubiquitin-like Modifier (SUMO)
      family of proteins have been established as critical events in the cellular
      response to a wide range of DNA damaging reagents and radiation; however, the
      detailed mechanism of SUMOylation in DNA damage response is not well understood.
      In this study, we used a nuclear magnetic resonance (NMR) spectroscopy-based
      metabolomics approach to examine the effect of an inhibitor of SUMO-mediated
      protein-protein interactions on MCF7 breast cancer cell response to radiation.
      Metabolomics is sensitive to changes in cellular functions and thus provides
      complementary information to other biological studies. The peptide inhibitor
      (SUMO interaction motif mimic, SIM) and a control peptide were stably expressed
      in MCF-7 cell line. Metabolite profiles of the cell lines before and after
      radiation were analyzed using solution NMR methods. Various statistical methods
      were used to isolate significant changes. Differences in the amounts of
      glutamine, aspartate, malate, alanine, glutamate and NADH between the SIM
      expressing and control cells suggest a role for SUMOylation in regulating
      mitochondrial function. This is also further verified following the metabolism of
      (13)C-labeled glutamine. The inability of the cells expressing the SIM peptide to
      increase production of the antioxidants carnosine and glutathione after radiation
      damage suggests an important role of SUMOylation in regulating the levels of
      antioxidants that protect cells from free radicals and reactive oxygen species
      generated by radiation. This study reveals previously unknown roles of
      SUMOylation in DNA damage response.

PMID- 20695453
TI  - Efficient syntheses of thiadiazole peptides.
AB  - Novel N-(Cbz-aminoacyl)thiosemicarbazides 3a-c were cyclized by treatment with
      sulfuric acid to give 1,3,4-thiadiazoles 4a-c. Compounds 4a-c reacted with N-(Cbz
      aminoacyl)- and -dipeptidoylbenzotriazoles to afford chirally pure 1,3,4
      thiadiazol-2-yl-substituted amino acids 6a-c and dipeptides 7a-c.

PMID- 20695454
TI  - Quantum dots based electrochemiluminescent immunosensor by coupling enzymatic
      amplification with self-produced coreactant from oxygen reduction.
AB  - A highly sensitive competitive immunosensor based on the electrochemiluminescence
      (ECL) of quantum dots (QDs) was proposed by coupling with an enzymatic
      amplification. The fabrication process of the immunosensor was traced with atomic
      force microscopic images and electrochemical impedance spectra. The strong
      cathodic ECL emission of the immobilized QDs could be detected at a relatively
      low emission potential. The reduction of dissolved oxygen during the cathodic
      process provided a self-produced coreactant, H(2)O(2), for the ECL emission.
      Using human IgG (HIgG) as a model protein, upon the immuno-recognition of the
      immobilized HIgG to its antibody labeled simply with horseradish peroxidase, the
      ECL intensity decreased due to the steric hindrance of the proteins to electron
      transfer. The decrease could be greatly amplified by an enzymatic cycle to
      consume the self-produced coreactant, leading to a wide calibration range of 0.05
      ng mL(-1) approximately 5 microg mL(-1) and a low limit of detection for the
      competitive immunoassay of HIgG. This immunosensor showed good stability and
      fabrication reproducibility. The immunoassays of practical samples showed
      acceptable results. This facile immunosensing strategy opened a new avenue for
      detection of proteins and application of QDs in ECL biosensing.

PMID- 20695455
TI  - The magnetism of (5MAP)2CuBr4 [5MAP = 5-methyl-2-aminopyridinium]: a quasi-2D or
      a 3D magnetic system?
AB  - In order to determine if its magnetic topology is actually two- or three
      dimensional (2D or 3D), the mechanism of the magnetic interaction in
      (5MAP)(2)CuBr(4), a previously thought quasi-2D antiferromagnet, is re-examined
      using the first-principles bottom-up methodology. Once the magnitude and sign of
      all unique magnetic interactions present in the room-temperature (5MAP)(2)CuBr(4)
      crystal are evaluated, it is found that, even at room temperature, the magnetic
      topology of the crystal corresponds to a 3D antiferromagnet. Such 3D nature
      cannot be determined by examination of the magnetic susceptibility curve, chi(T),
      because it is found that the chi(T) curve computed using this 3D magnetic
      topology is very similar to that obtained using a 2D model where all interplane
      interactions have been deleted. However, its 3D magnetic dimensionality can be
      confirmed by examination of the shape of the magnetization curve, M(H); the
      computed curve is similar to the experimental one for the 3D case.

PMID- 20695456
TI  - Quantifying transcription of clinically relevant immobilized DNA within a
      continuous flow microfluidic reactor.
AB  - Flow-through reactors are commonly used to control and optimize reagent delivery
      and product removal. Although recent research suggests that transcription
      reactions using picogram quantities of cDNA produce RNA efficiently in a flow
      through microreactor, there has not been a detailed study on the mass transport
      and reagent dependence of microfluidic transcription reactions. We present a
      novel microreactor that contains H5 influenza cDNA immobilized directly onto the
      reactor walls to study the kinetics and reagent dependence of in vitro
      transcription reactions on a microfluidic platform. Enzyme and the rNTP substrate
      continuously flow over the cDNA and create RNA, which flows to a downstream
      collection well. Using nanogram quantities of cDNA, we found that enzyme limiting
      conditions caused by the concentration of cDNA in a small-volume microreactor
      channel may be partially overcome as the enzyme binds and concentrates near the
      channel wall. Kinetics confirm this phenomenon and show that the timescale for
      enzyme binding can be approximated by t(f) = cDNA/Q[E]. Surprisingly, on-chip
      transcription reactions have a strong dependence on the rNTP concentration from 5
      to 9 mM despite a low consumption rate of rNTP molecules that is largely
      independent of the flow rate. Faster flow rates decrease the time it takes to
      fill DNA promoter sites with enzyme while additionally refreshing rNTP and
      MgCl(2) to allow for a greater consumption of rNTP. These two effects cause
      reactions with higher concentrations of cDNA in the reactor channel to have a
      greater dependence on the flow rate. At high flow rates (>0.37 nL/s), the
      reaction rate begins to drop, likely because of the release and escape of enzyme
      molecules from the cDNA layer. This critical flow rate can be predicted by a new
      modified Peclet number, Pe(m) = L(c)V/D, where L(c) is the full length of the
      tightly packed cDNA molecules, V is the velocity at the DNA/fluid interface, and
      D is the diffusivity of the enzyme molecule. Together, these insights can inspire
      reactor designs for a variety of applications.

PMID- 20695457
TI  - Glyphosate-based herbicides produce teratogenic effects on vertebrates by
      impairing retinoic acid signaling.
AB  - The broad spectrum herbicide glyphosate is widely used in agriculture worldwide.
      There has been ongoing controversy regarding the possible adverse effects of
      glyphosate on the environment and on human health. Reports of neural defects and
      craniofacial malformations from regions where glyphosate-based herbicides (GBH)
      are used led us to undertake an embryological approach to explore the effects of
      low doses of glyphosate in development. Xenopus laevis embryos were incubated
      with 1/5000 dilutions of a commercial GBH. The treated embryos were highly
      abnormal with marked alterations in cephalic and neural crest development and
      shortening of the anterior-posterior (A-P) axis. Alterations on neural crest
      markers were later correlated with deformities in the cranial cartilages at
      tadpole stages. Embryos injected with pure glyphosate showed very similar
      phenotypes. Moreover, GBH produced similar effects in chicken embryos, showing a
      gradual loss of rhombomere domains, reduction of the optic vesicles, and
      microcephaly. This suggests that glyphosate itself was responsible for the
      phenotypes observed, rather than a surfactant or other component of the
      commercial formulation. A reporter gene assay revealed that GBH treatment
      increased endogenous retinoic acid (RA) activity in Xenopus embryos and
      cotreatment with a RA antagonist rescued the teratogenic effects of the GBH.
      Therefore, we conclude that the phenotypes produced by GBH are mainly a
      consequence of the increase of endogenous retinoid activity. This is consistent
      with the decrease of Sonic hedgehog (Shh) signaling from the embryonic dorsal
      midline, with the inhibition of otx2 expression and with the disruption of
      cephalic neural crest development. The direct effect of glyphosate on early
      mechanisms of morphogenesis in vertebrate embryos opens concerns about the
      clinical findings from human offspring in populations exposed to GBH in
      agricultural fields.

PMID- 20695458
TI  - Surface attachment of protein fibrils via covalent modification strategies.
AB  - Chemical control of surface functionality and topography is an essential
      requirement for many technological purposes. In particular, the covalent
      attachment of monomeric proteins to surfaces has been the object of intense
      studies in recent years, for applications as varied as electrochemistry, immuno
      sensing, and the production of biocompatible coatings. Little is known, however,
      about the characteristics and requirements underlying surface attachment of
      supramolecular protein nanostructures. Amyloid fibrils formed by the self
      assembly of peptide and protein molecules represent one important class of such
      structures. These highly organized beta-sheet-rich assemblies are a hallmark of a
      range of neurodegenerative disorders, including Alzheimer's disease and type II
      diabetes, but recent findings suggest that they have much broader significance,
      potentially representing the global free energy minima of the energy landscapes
      of proteins and having potential applications in material science. In this paper,
      we describe strategies for attaching amyloid fibrils formed from different
      proteins to gold surfaces under different solution conditions. Our methods
      involve the reaction of sulfur containing small molecules (cystamine and 2
      iminothiolane) with the amyloid fibrils, enabling their covalent linkage to gold
      surfaces. We demonstrate that irreversible attachment using these approaches
      makes possible quantitative analysis of experiments using biosensor techniques,
      such as quartz crystal microbalance (QCM) assays that are revolutionizing our
      understanding of the mechanisms of amyloid growth and the factors that determine
      its kinetic behavior. Moreover, our results shed light on the nature and relative
      importance of covalent versus noncovalent forces acting on protein
      superstructures at metal surfaces.

PMID- 20695459
TI  - Convenient RNA synthesis using a phosphoramidite possessing a biotinylated
      photocleavable group.
AB  - A convenient RNA synthesis using a biotin-streptavidin interaction and a
      photocleavable protecting group is described. The biotinylated photocleavable
      group was introduced at the 2'-position of the uridine derivative. Using the
      phosphoramidite 12, we attempted the synthesis of a 21mer RNA, which is pure
      enough to show potent RNAi activity compared with a conventionally prepared and
      HPLC-purified 21mer RNA with the same sequence.

PMID- 20695460
TI  - Differential cellular responses to protein adducts of naphthoquinone and
      monocrotaline pyrrole.
AB  - Protein-xenobiotic adducts are byproducts of xenobiotic metabolism. While there
      is a correlation between protein adduction and target organ toxicity, a cause and
      effect relationship is not often clear. Naphthoquinone (NQ) and monocrotaline
      pyrrole (MCTP) are two pneumotoxic electrophiles that form covalent adducts with
      a similar select group of proteins rich in reactive thiols. In this study, we
      treated human pulmonary artery endothelial cells (HPAEC) with NQ, MCTP, or
      preformed NQ or MCTP adducts to the protein galectin-1 (gal-1) and examined
      indicators of reactive oxygen species (ROS) oxidative injury, markers of
      apoptosis (caspase-3 and annexin V), and gene responses of cellular stress. ROS
      production was assayed fluorescently using CM-H(2)DCFDA. NQ adducts to gal-1 (NQ
      gal) produced 183% more intracellular ROS than gal-1 alone (p < 0.0001). Caspase
      3 activity and annexin V staining of phosphatidylserine were used to assess
      apoptotic activity in treated cells. HPAEC exposed to MCTP-gal had increases in
      both caspase-3 activation and membrane translocation of annexin V relative to gal
      1 alone (p < 0.0001). Direct application of NQ produced significantly more ROS
      and induced significant caspase-3 activation, whereas MCTP did not. Human
      bronchial epithelial cells were also exposed to MCTP-gal and found to have
      significant increases in both caspase-3 activation and annexin V staining in
      comparison to that of gal-1 (p < 0.05). Western blot analysis showed that both NQ
      and MCTP significantly induced the Nrf2 mediated stress response pathway despite
      differences in ROS generation. ER stress was not induced by either adducts or
      parent compounds as seen by quantitative RT-PCR, but HOX-1 expression was
      significantly induced by NQ-gal and MCTP alone. Electrophile adduction to gal-1
      produces different cytotoxic effects specific to each reactive intermediate.

PMID- 20695461
TI  - Synthesis and solution phase characterization of strongly photooxidizing
      heteroleptic Cr(III) tris-dipyridyl complexes.
AB  - We report the preparation and characterization of Cr(III) coordination complexes
      featuring the dimethyl 2,2'-bipyridine-4,4'-dicarboxylate (4-dmcbpy) ligand:
      [(phen)(2)Cr(4-dmcbpy)](OTf)(3) (1), [(Ph(2)phen)(2)Cr(4-dmcbpy)](OTf)(3) (4),
      [(Me(2)bpy)(2)Cr(4-dmcbpy)](OTf)(3) (7), and [Cr(4-dmcbpy)(3)](BF(4))(3) (8),
      where phen is 1,10-phenanthroline, Ph(2)phen is 4,7-diphenyl-1,10-phenanthroline,
      and Me(2)bpy is 4,4'-dimethyl-2,2'-bipyridine. Static and nanosecond time
      resolved absorption and emission properties of these complexes dissolved in
      acidic aqueous (1 M HCl) solutions are reported. Emission spectra collected at
      297 K show a narrow spectrum with an emission maximum ranging from 732 nm (1) to
      742 nm (4). The emissive state is thermally activated and decays via first order
      kinetics at all temperatures explored (283 to 353 K). At 297 K the observed
      lifetime ranges from 7.7 micros (8) to 108 micros (4). The photophysical data
      suggest that in these acidic aqueous environments these complexes store
      approximately 1.7 eV for multiple microseconds at room temperature. Of the
      heteroleptic species, complex 4 shows the greatest absorption of visible
      wavelengths (epsilon = 1270 M(-1) cm(-1) at 491 nm), and homoleptic complex 8 has
      improved absorption at visible wavelengths over [Cr(bpy)(3)](3+). The
      electrochemical properties of 1, 4, 7, and 8 were investigated by cyclic
      voltammetry. It is found that inclusion of 4-dmcbpy shifts the "Cr(III/II)"
      E(1/2) by +0.22 V compared to those of homoleptic parent complexes, with the
      first reduction event occurring at -0.26 V versus Fc(+)/Fc for 8. The
      electrochemical and photophysical data allow for excited state potentials to be
      determined: for 8, Cr(III*/II) lies at +1.44 V versus ferrocenium/ferrocene
      (approximately +2 V vs NHE), placing it among the most powerful photooxidants
      reported.

PMID- 20695462
TI  - Aqueous boundary layers related to oral absorption of a drug: from dissolution of
      a drug to carrier mediated transport and intestinal wall metabolism.
AB  - The aqueous boundary layer (ABL) affects various aspects of oral absorption of a
      drug, from dissolution of the drug to the apparent K(m) value of intestinal wall
      metabolism and carrier mediated transport. However, the importance of ABL has
      often been entirely ignored in oral absorption investigation. In this minireview,
      the effect of ABL on oral absorption of a drug is discussed in an easy-to
      understand manner. This review starts with an introduction of the boundary layer
      theory with many illustrations (and links to public web movies visualizing the
      ABL), and then discusses some specific cases of interest in pharmaceutical
      science, such as dissolution of floating drug particles in the USP paddle
      apparatus. The effect of the boundary layer on the membrane permeation is also
      discussed from the viewpoint of structure permeability relationship, carrier
      mediated transport/metabolism and estimation of the fraction of a dose absorbed
      for poor solubility compounds.

PMID- 20695463
TI  - Transnasal delivery of methotrexate to brain tumors in rats: a new strategy for
      brain tumor chemotherapy.
AB  - Brain tumors are one of the most lethal and difficult to treat. Their treatment
      is limited by the inadequate delivery of antitumor drugs to the tumor. In order
      to overcome this limitation, the possibility of the nose-brain direct transport
      pathway was evaluated using methotrexate (MTX) as a model antitumor agent. The
      direct transport of nasal MTX to the cerebrospinal fluid (CSF) was examined by
      comparing the concentration of MTX in the plasma and the CSF after
      intraperitoneal (IP) and intranasal (IN) administrations. The brain uptake of MTX
      was evaluated based on a multiple-time/graphical analysis by measuring the
      concentration of MTX in the plasma and in the brain. The feasibility of nasal
      chemotherapy was examined by three nasal dosings of MTX to tumor-bearing rats in
      vivo at two day intervals with peritoneal application as a positive control. MTX
      showed a significant inhibitory effect on the in vitro growth of 9L glioma cells
      with 50% growth inhibitory concentration at 7.99 ng/mL. The pharmacokinetic
      studies clarified the significant direct transport of MTX from nasal cavity both
      to the CSF and to the brain. Nasal chemotherapy with MTX significantly reduced
      the tumor weight as compared to nontreatment control and IP group. The strategy
      to utilize the nose-brain direct transport can be applicable to a new therapeutic
      system not only for brain tumors but also for other central nervous system
      disorders such as neurodegenerative diseases.

PMID- 20695465
TI  - Real-time management of an urban groundwater well field threatened by pollution.
AB  - We present an optimal real-time control approach for the management of drinking
      water well fields. The methodology is applied to the Hardhof field in the city of
      Zurich, Switzerland, which is threatened by diffuse pollution. The risk of
      attracting pollutants is higher if the pumping rate is increased and can be
      reduced by increasing artificial recharge (AR) or by adaptive allocation of the
      AR. The method was first tested in offline simulations with a three-dimensional
      finite element variably saturated subsurface flow model for the period January
      2004-August 2005. The simulations revealed that (1) optimal control results were
      more effective than the historical control results and (2) the spatial
      distribution of AR should be different from the historical one. Next, the
      methodology was extended to a real-time control method based on the Ensemble
      Kalman Filter method, using 87 online groundwater head measurements, and tested
      at the site. The real-time control of the well field resulted in a decrease of
      the electrical conductivity of the water at critical measurement points which
      indicates a reduced inflow of water originating from contaminated sites. It can
      be concluded that the simulation and the application confirm the feasibility of
      the real-time control concept.

PMID- 20695464
TI  - Pulsed EPR determination of the distance between heme iron and FMN centers in a
      human inducible nitric oxide synthase.
AB  - Mammalian nitric oxide synthase (NOS) is a homodimeric flavo-hemoprotein that
      catalyzes the oxidation of L-arginine to nitric oxide (NO). Regulation of NO
      biosynthesis by NOS is primarily through control of interdomain electron transfer
      (IET) processes in NOS catalysis. The IET from the flavin mononucleotide (FMN) to
      heme domains is essential in the delivery of electrons required for O(2)
      activation in the heme domain and the subsequent NO synthesis by NOS. The NOS
      output state for NO production is an IET-competent complex of the FMN-binding
      domain and heme domain, and thereby it facilitates the IET from the FMN to the
      catalytic heme site. The structure of the functional output state has not yet
      been determined. In the absence of crystal structure data for NOS holoenzyme, it
      is important to experimentally determine the Fe...FMN distance to provide a key
      calibration for computational docking studies and for the IET kinetics studies.
      Here we used the relaxation-induced dipolar modulation enhancement (RIDME)
      technique to measure the electron spin echo envelope modulation caused by the
      dipole interactions between paramagnetic FMN and heme iron centers in the
      [Fe(III)][FMNH(*)] (FMNH(*): FMN semiquinone) form of a human inducible NOS
      (iNOS) bidomain oxygenase/FMN construct. The FMNH(*)...Fe distance has been
      directly determined from the RIDME spectrum. This distance (18.8 +/- 0.1 A) is in
      excellent agreement with the IET rate constant measured by laser flash photolysis
      [Feng, C. J.; Dupont, A.; Nahm, N.; Spratt, D.; Hazzard, J. T.; Weinberg, J.;
      Guillemette, J.; Tollin, G.; Ghosh, D. K. J. Biol. Inorg. Chem. 2009, 14, 133
      142].

PMID- 20695466
TI  - Contribution of Li-ion batteries to the environmental impact of electric
      vehicles.
AB  - Battery-powered electric cars (BEVs) play a key role in future mobility
      scenarios. However, little is known about the environmental impacts of the
      production, use and disposal of the lithium ion (Li-ion) battery. This makes it
      difficult to compare the environmental impacts of BEVs with those of internal
      combustion engine cars (ICEVs). Consequently, a detailed lifecycle inventory of a
      Li-ion battery and a rough LCA of BEV based mobility were compiled. The study
      shows that the environmental burdens of mobility are dominated by the operation
      phase regardless of whether a gasoline-fueled ICEV or a European electricity
      fueled BEV is used. The share of the total environmental impact of E-mobility
      caused by the battery (measured in Ecoindicator 99 points) is 15%. The impact
      caused by the extraction of lithium for the components of the Li-ion battery is
      less than 2.3% (Ecoindicator 99 points). The major contributor to the
      environmental burden caused by the battery is the supply of copper and aluminum
      for the production of the anode and the cathode, plus the required cables or the
      battery management system. This study provides a sound basis for more detailed
      environmental assessments of battery based E-mobility.

PMID- 20695467
TI  - Reactions of yttrium and scandium atoms with acetylene: a matrix isolation
      infrared spectroscopic and theoretical study.
AB  - Laser-ablated yttrium and scandium metal atoms have been codeposited at 4 K with
      acetylene in excess argon. Products, Y(C(2)H(2)), HYCCH, HScCCH(-), and HScScCCH(
      ), have been formed in the present experiments and characterized using infrared
      spectroscopy on the basis of the results of the isotopic shifts, mixed isotopic
      splitting patterns, stepwise annealing, the change of reagent concentration and
      laser energy, and the comparison with theoretical predictions. Density functional
      theory calculations have been performed on these molecules. The agreement between
      the experimental and calculated vibrational frequencies, relative absorption
      intensities, and isotopic shifts supports the identification of these molecules
      from the matrix infrared spectra. Plausible reaction mechanisms have been
      proposed to account for the formation of these molecules.

PMID- 20695468
TI  - Structural relaxation of vapor-deposited water, methanol, ethanol, and 1-propanol
      films studied using low-energy ion scattering.
AB  - Glassy thin films of water, methanol, ethanol, and 1-propanol were prepared by
      deposition from the gas phase at 20 K. Relaxation of their surface and bulk
      structures was investigated by measuring temperature evolutions of H(+), H(-),
      and total yields in low-energy H(2)(+) scattering. The surface structure of a
      methanol film changes at temperatures of about 20 K below the glass transition
      temperature (T(g) = 103 K) because of enhanced diffusivity of molecules at the
      surface. Both surface and bulk structures change at around T(g) for ethanol, but
      the structure of the 1-propanol film is unchanged at temperatures higher than
      T(g), indicating that the vapor-deposited 1-propanol glass is more stable than
      the liquid-quenched one. These behaviors strongly suggest that the configurations
      of molecules in the vapor-deposited glass differ significantly from those in the
      liquid-quenched glass and that the aliphatic-chain length plays an important role
      in structural relaxation. The surface (bulk) structure of the water film changes
      gradually (is invariant) across T(g), suggesting that the relaxation and glass
      transition processes differ significantly between those of water and alcohols.

PMID- 20695469
TI  - Enhanced photostability of the anthracene chromophore in aqueous medium upon
      protein encapsulation.
AB  - In the present work, 9-anthraceneacetic acid (1) has been selected as a simple,
      water-compatible derivative of the anthracene chromophore to investigate the
      photophysical and photochemical behavior upon binding to human and bovine serum
      albumins (HSA and BSA) and alpha-acid glycoproteins (HAAG and BAAG). The UV-vis
      absorption spectrum of 1 exhibited the typical four maxima between 320 and 400
      nm, which were slightly red-shifted in the presence of proteins. These minor
      changes suggested the formation of 1@protein complexes; their stoichiometry (1:1)
      was determined by means of the corresponding Job plots. As expected, the
      fluorescence spectrum of 1 in phosphate-buffered saline (PBS) consisted of a
      structured emission with maxima between 390 and 470 nm. The addition of
      increasing amounts of HSA resulted in a decrease in the emission intensity. In
      the presence of BSA, HAAG, or BAAG, the same trend was observed, although the
      changes were less pronounced. The determination of binding constants was achieved
      from fluorescence titration, considering one (AAGs) or two (SAs) binding sites.
      The binding constants (K(B)) were found to be 2.3 x 10(6) M(-1) (HAAG), 2.4 x
      10(6) M(-1) (BAAG), 4.57 x 10(4)/1.45 x 10(6) M(-1) (HSA), and 1.44 x 10(4)/1.20
      x 10(6) M(-1) (BSA). Binding within two different sites of SAs was confirmed by
      displacement experiments using warfarin and ibuprofen as site I and site II
      probes, respectively. Laser flash photolysis of 1 at lambda(exc) = 355 nm in
      PBS/air gave rise to several transient species; by contrast, in the presence of 1
      equiv of proteins, only the triplet excited state was detected. Moreover, the
      triplet lifetime (tau(T)) monitored at 420 nm lengthened considerably (up to 50
      fold) in the protein media. This can be attributed to a slower deactivation of
      the species inside the protein binding pockets, where an exceptional
      microenvironment provides protection from attack by a second molecule of 1,
      oxygen, or other reagents. In agreement with the results from fluorescence
      titration, the presence of two binding sites in SAs was revealed by two different
      triplet lifetimes; by contrast, only one tau(T) value was found for HAAG and
      BAAG. The major, longer-lived component under nonsaturating conditions was
      assigned to (1@SA)(II), while the minor component was assigned to (1@SA)(I).
      Irradiation of 1 at 350 nm in PBS/air led to anthraquinone as a major product. In
      the presence of proteins, the degree of conversion was markedly lower than in
      PBS, as revealed by the photodegradation kinetics monitored through the
      absorbance changes at 367 nm. Thus, a dramatic protection from photooxidation is
      provided within the protein microenvironment.

PMID- 20695470
TI  - An ab initio molecular dynamics study on the hydrolysis of the Po(IV) aquaion in
      water.
AB  - Po(IV) in water has been studied by means of Car-Parrinello molecular dynamics
      (CPMD) simulations. A new Trouiller-Martins pseudopotential for Po(IV) has been
      developed. This pseudopotential was tested by comparing the structure and
      energetics of small [Po(H(2)O)(n)(OH)(m)](4-m) clusters optimized quantum
      mechanically. CP-MD simulations of 1 Po + 60 H(2)O were carried out starting from
      three different degrees of hydrolysis of the aquaion (m = 0, 2, and 3), in order
      to check the stability of the hydrolyzed forms under the simulation conditions.
      The three simulations converge to a description of the solution where the same
      hydrolyzed species are present. Dynamics of the octahydrate aquaion in water
      indicates that dehydration couples to hydrolysis processes, and the total
      coordination number decreases with the hydrolysis degree. The time evolution of
      the initial [Po(H(2)O)(8)](4+) aquaion in aqueous solution indicates that
      hydrolysis precedes to dehydration in the process from aquaion to hydroxoaquaion.
      Structural and dynamical properties of the ligands in the first coordination
      shell are analyzed. The power spectra and its contribution from fragments of the
      first coordination shell are also examined.

PMID- 20695471
TI  - All-atom multiscale simulation of cowpea chlorotic mottle virus capsid swelling.
AB  - An all-atom multiscale computational modeling approach, molecular dynamics/order
      parameter extrapolation (MD/OPX), has recently been developed for simulating
      large bionanosystems. It accelerates MD simulations and addresses rapid atomistic
      fluctuations and slowly varying nanoscale dynamics of bionanosystems
      simultaneously. With modules added to account for water molecules and ions,
      MD/OPX is applied to simulate the swelling of cowpea chlorotic mottle virus
      (CCMV) capsid solvated in a host medium in this study. Simulation results show
      that the N-terminal arms of capsid proteins undergo large deviations from the
      initial configurations with their length extended quickly during the early stage
      of capsid swelling. The capsid swelling is a symmetry-breaking process involving
      local initiation and front propagation. The capsid swelling rate is approximately
      0.25 nm/ns (npn) during the early stage of the simulation, and propagation of the
      structural transition across the capsid is roughly 0.6 npn. The system conditions
      that affect swelling of the capsid are analyzed. Prospects for creating a phase
      diagram for CCMV capsid swelling and using predictions to guide experiments are
      discussed.

PMID- 20695472
TI  - Identification of a naturally occurring rexinoid, honokiol, that activates the
      retinoid X receptor.
AB  - Screening of a total of 86 crude drugs for retinoid X receptor (RXR) ligands
      demonstrated that the methanol extract of the bark of Magnolia obovata markedly
      activated the transcriptional activity of RXRalpha in luciferase reporter assays.
      Thereafter, honokiol (1) was isolated as a constituent able to activate RXR
      selectively as a natural rexinoid, but not RARalpha. The activity of 1 was more
      potent than those of phytanic acid and docosahexaenoic acid, both of which are
      known to be natural RXR agonists. Honokiol (1) is capable of activating a RXR/LXR
      heterodimer, resulting in the induction of ATP-binding cassette transporter A1
      mRNA and protein expression in RAW264.7 cells, as well as an increase in
      [(3)H]cholesterol efflux from peritoneal macrophages. These effects of 1 were
      enhanced synergistically in the presence of an LXR agonist, 22(R)
      hydroxycholesterol. The results obtained demonstrate that 1, a newly identified
      natural rexinoid, regulates the functions of RXR/LXR heterodimer and abrogates
      foam cell formation by the induction of ABCA1 via activation of the RXR/LXR
      heterodimer.

PMID- 20695473
TI  - Host-guest chemistry of dendrimer-drug complexes. 5. Insights into the design of
      formulations for noninvasive delivery of heparin revealed by isothermal titration
      calorimetry and NMR studies.
AB  - The host-guest chemistry of dendrimer-biomacromolecule complexes is of great
      significance to both design and optimization of dendrimer-based drug delivery and
      host-guest systems. Here, we characterized the interactions between dendrimer and
      heparin by isothermal titration calorimetry (ITC), (1)H nuclear magnetic
      resonance ((1)H NMR), pulsed-field gradient (PFG) NMR, nuclear Overhauser effect
      spectroscopy (NOESY), and atomic force microscopy (AFM) studies. The calorimetric
      results suggest that miscellaneous aggregates are formed at different stages when
      heparin was titrated into a dendrimer solution: dendrimer-heparin "necklace"
      structures, followed by the formation of larger and more stable aggregates, and
      then macroscopic complexes which precipitate from the solution. The binding
      process is significantly influenced by dendrimer generation, surface
      functionality, and ion strength, indicating that the formation of dendrimer
      heparin aggregates is predominantly driven by electrostatic interactions. The NMR
      results confirm the dendrimer-heparin binding models established by calorimetric
      measurement and present a new type of dendrimer-heparin aggregates at higher
      heparin/dendrimer molar ratios. Formulations containing generation 5 (G5) PAMAM
      dendrimers with a heparin/G5 molar ratio of 0.5-1.2 are proposed as effective
      ones for the treatment of thrombosis in noninvasive delivery routes such as
      nasal, pulmonary, transdermal, and oral routes. The combination of ITC and NMR in
      this study provides new insight into the interactions between globular and linear
      polymers and the delivery of macromolecular therapeutics such as heparin by
      dendrimers.

PMID- 20695474
TI  - Nocapyrones A-D, gamma-pyrones from a Nocardiopsis strain isolated from the
      marine sponge Halichondria panicea.
AB  - Four new gamma-pyrones, nocapyrones A-D (1-4), were isolated from an organic
      extract of the Nocardiopsis strain HB383, which was isolated from the marine
      sponge Halichondria panicea. These are the first gamma-pyrones reported from a
      Nocardiopsis strain. The structures were elucidated on the basis of one- and two
      dimensional NMR experiments and supported by HPLC-UV/MS and HRESIMS analyses. The
      biosynthesis of nocapyrone A was investigated by feeding experiments with (13)C
      labeled compounds. In addition, one diketopiperazine, which was only known as a
      synthetic compound before, was isolated. The bioactivies of 1, 2, and the
      diketopiperazine were evaluated in a panel of assays.

PMID- 20695475
TI  - Water in cavity-ligand recognition.
AB  - We use explicit solvent molecular dynamics simulations to estimate free energy,
      enthalpy, and entropy changes along the cavity-ligand association coordinate for
      a set of seven model systems with varying physicochemical properties. Owing to
      the simplicity of the considered systems we can directly investigate the role of
      water thermodynamics in molecular recognition. A broad range of thermodynamic
      signatures is found in which water (rather than cavity or ligand) enthalpic or
      entropic contributions appear to drive cavity-ligand binding or rejection. The
      unprecedented, nanoscale picture of hydration thermodynamics can help the
      interpretation and design of protein-ligand binding experiments. Our study opens
      appealing perspectives to tackle the challenge of solvent entropy estimation in
      complex systems and for improving molecular simulation models.

PMID- 20695476
TI  - Iodide as a fluorescence quencher and promoter--mechanisms and possible
      implications.
AB  - In this work, fluorescence correlation spectroscopy (FCS) was used to investigate
      the effects of potassium iodide (KI) on the electronic-state population kinetics
      of a range of organic dyes in the visible wavelength range. Apart from a heavy
      atom effect promoting intersystem crossing to the triplet states in all dyes, KI
      was also found to enhance the triplet-state decay rate by a charge-coupled
      deactivation. This deactivation was only found for dyes with excitation maximum
      in the blue range, not for those with excitation maxima at wavelengths in the
      green range or longer. Consequently, under excitation conditions sufficient for
      triplet state formation, KI can promote the triplet state buildup of one dye and
      reduce it for another, red-shifted dye. This anticorrelated, spectrally separable
      response of two different dyes to the presence of one and the same agent may
      provide a useful readout for biomolecular interaction and microenvironmental
      monitoring studies. In contrast to the typical notion of KI as a fluorescence
      quencher, the FCS measurements also revealed that when added in micromolar
      concentrations KI can act as an antioxidant, promoting the recovery of photo
      oxidized fluorophores. However, in millimolar concentrations KI also reduces
      intact, fluorescently viable fluorophores to a considerable extent. In aqueous
      solutions, for the dye Rhodamine Green, an optimal concentration of KI of
      approximately 5 mM can be defined at which the fluorescence signal is maximized.
      This concentration is not high enough to allow full triplet state quenching.
      Therefore, as a fluorescence enhancement agent, it is primarily the antioxidative
      properties of KI that play a role.

PMID- 20695477
TI  - Quantum dots modulate leukocyte adhesion and transmigration depending on their
      surface modification.
AB  - Although different nanosized materials, including quantum dots (QDs), are
      intended to be used for biomedical applications, their interactions with
      microvessels and their inflammatory potential are largely unknown. In this in
      vivo study we report that leukocyte recruitment is modulated in the presence of
      quantum dots. We found that the surface chemistry of QDs strongly affects their
      localization in postcapillary venules, their uptake by perivascular macrophages,
      and their potential to modify steps of leukocyte recruitment.

PMID- 20695478
TI  - Radially aligned, electrospun nanofibers as dural substitutes for wound closure
      and tissue regeneration applications.
AB  - This paper reports the fabrication of scaffolds consisting of radially aligned
      poly(epsilon-caprolactone) nanofibers by utilizing a collector composed of a
      central point electrode and a peripheral ring electrode. This novel class of
      scaffolds was able to present nanoscale topographic cues to cultured cells,
      directing and enhancing their migration from the periphery to the center. We also
      established that such scaffolds could induce faster cellular migration and
      population than nonwoven mats consisting of random nanofibers. Dural fibroblast
      cells cultured on these two types of scaffolds were found to express type I
      collagen, the main extracellular matrix component in dural mater. The type I
      collagen exhibited a high degree of organization on the scaffolds of radially
      aligned fibers and a haphazard distribution on the scaffolds of random fibers.
      Taken together, the scaffolds based on radially aligned, electrospun nanofibers
      show great potential as artificial dural substitutes and may be particularly
      useful as biomedical patches or grafts to induce wound closure and/or tissue
      regeneration.

PMID- 20695479
TI  - Discovery of new inhibitors of Schistosoma mansoni PNP by pharmacophore-based
      virtual screening.
AB  - Schistosomiasis is considered the second most important tropical parasitic
      disease, with severe socioeconomic consequences for millions of people worldwide.
      Schistosoma mansoni , one of the causative agents of human schistosomiasis, is
      unable to synthesize purine nucleotides de novo, which makes the enzymes of the
      purine salvage pathway important targets for antischistosomal drug development.
      In the present work, we describe the development of a pharmacophore model for
      ligands of S. mansoni purine nucleoside phosphorylase (SmPNP) as well as a
      pharmacophore-based virtual screening approach, which resulted in the
      identification of three thioxothiazolidinones (1-3) with substantial in vitro
      inhibitory activity against SmPNP. Synthesis, biochemical evaluation, and
      structure-activity relationship investigations led to the successful development
      of a small set of thioxothiazolidinone derivatives harboring a novel chemical
      scaffold as new competitive inhibitors of SmPNP at the low-micromolar range.
      Seven compounds were identified with IC(50) values below 100 MUM. The most potent
      inhibitors 7, 10, and 17 with IC(50) of 2, 18, and 38 MUM, respectively, could
      represent new potential lead compounds for further development of the therapy of
      schistosomiasis.

PMID- 20695480
TI  - Benchmark performance of MultiCASE Inc. software in Ames mutagenicity set.
AB  - The predictive performances of MC4PC were evaluated using its learning machine
      functionality. Its superior characteristics are demonstrated in this following up
      study using the newly published Ames mutagenicity benchmark set.

PMID- 20695481
TI  - 3'-Sulfo-Le(x) is important for regulation of integrin subunit alphaV.
AB  - Carbohydrate structures with a 3'-sulfo betaGal linkage, such as 3'-sulfo-Le(x),
      can be synthesized by Gal:3-O-sulfotransferase-2 (Gal3ST-2) catalysis, but little
      is known about their roles in many biological processes. To investigate the role
      of Gal3ST-2 and its product 3'-sulfo-Le(x), we depleted Gal3ST-2 via siRNA and
      added exogenous Lewis-x trisaccharide 3'-sulfate sodium salt in human SMMC7721
      hepatoma cells. After siRNA transfection, a striking morphological change in
      SMMC7721 hepatoma cells from polygon to shuttle shape and a significant decrease
      in the level of adhesion to sL-selectin, HUVEC, fibronectin, vitronectin, and
      fibrinogen were observed. The expression of integrin subunit alphaV was markedly
      downregulated, and 3'-sulfated subunit alphaV almost disappeared in the
      transfectants. The level of cell surface integrin alphaVbeta3 was reduced
      simultaneously, although total subunit beta3 underwent almost no change. After
      treatment with exogenous Lewis-x 3'-sulfate, cellular integrin subunit alphaV was
      upregulated and the level of cell surface integrin alphaVbeta3 was elevated.
      Interestingly, knockdown of Gal3ST-2 expression effectively inhibited cell
      proliferation, and the result was significantly correlated with the decrease in
      the levels of ILK, phosphorylated AKT, and ERK. On the other hand, treatment with
      Lewis-x trisaccharide 3'-sulfate sodium salt greatly upregulated the
      phosphorylation of AKT and ERK. Our results also indicated that downregulation of
      Gal3ST-2 via siRNA transfection was associated with the decrease in the level of
      expression of anti-apoptotic protein, Bcl-2, with a consequent decrease in the
      ratios for Bcl-2 to Bax. By exposure to Lewis-x trisaccharide 3'-sulfate sodium
      salt, the apoptotic response of cells was inhibited. Therefore, Gal3ST-2 and its
      product, 3'-sulfo-Le(x), were involved in regulation of integrin subunit alphaV
      and might be associated with cancer cell regulation.

PMID- 20695482
TI  - A kinetic and isotope effect investigation of the urease-catalyzed hydrolysis of
      hydroxyurea.
AB  - The urease-catalyzed hydrolysis of hydroxyurea is known to exhibit biphasic
      kinetics, showing a rapid burst phase followed by a slow plateau phase. Kinetic
      isotope effects for both phases of this reaction were measured at pH 6.0 and 25 
      degrees C. The observed nitrogen isotope effects for the ammonia leaving group
      [(15)(V/K)(NH(3))] were 1.0016 +/- 0.0005 during the burst phase and 1.0019 +/-
      0.0007 during the plateau phase, while those for the hydroxylamine leaving group
      [(15)(V/K)(NH(2)OH)] were 1.0013 +/- 0.0005 for the burst phase and 1.0022 +/-
      0.0003 for the plateau phase. These isotope effects are consistent with a rate
      determining step that occurs prior to breaking either of the two possible C-N
      bonds. The observed carbonyl carbon isotope effects [(13)(V/K)] were 1.0135 +/-
      0.0003 during the burst phase and 1.0178 +/- 0.0003 during the plateau phase. The
      similarity of the magnitude of the carbon isotope effects argues for formation of
      a common intermediate during both phases.

PMID- 20695483
TI  - Structural characterization of GNNQQNY amyloid fibrils by magic angle spinning
      NMR.
AB  - Several human diseases are associated with the formation of amyloid aggregates,
      but experimental characterization of these amyloid fibrils and their oligomeric
      precursors has remained challenging. Experimental and computational analysis of
      simpler model systems has therefore been necessary, for instance, on the peptide
      fragment GNNQQNY7-13 of yeast prion protein Sup35p. Expanding on a previous
      publication, we report here a detailed structural characterization of GNNQQNY
      fibrils using magic angle spinning (MAS) NMR. On the basis of additional chemical
      shift assignments we confirm the coexistence of three distinct peptide
      conformations within the fibrillar samples, as reflected in substantial chemical
      shift differences. Backbone torsion angle measurements indicate that the basic
      structure of these coexisting conformers is an extended beta-sheet. We
      structurally characterize a previously identified localized distortion of the
      beta-strand backbone specific to one of the conformers. Intermolecular contacts
      are consistent with each of the conformers being present in its own parallel and
      in-register sheet. Overall the MAS NMR data indicate a substantial difference
      between the structure of the fibrillar and crystalline forms of these peptides,
      with a clearly increased complexity in the GNNQQNY fibril structure. These
      experimental data can provide guidance for future work, both experimental and
      theoretical, and provide insights into the distinction between fibril growth and
      crystal formation.

PMID- 20695484
TI  - Computational modeling toward understanding agonist binding on dopamine 3.
AB  - The dopamine 3 (D3) receptor is a promising therapeutic target for the treatment
      of nervous system disorders, such as Parkinson's disease, and current research
      interests primarily focus on the discovery/design of potent D3 agonists. Herein,
      a well-designed computational protocol, which combines pharmacophore
      identification, homology modeling, molecular docking, and molecular dynamics (MD)
      simulations, was employed to understand the agonist binding on D3 aiming to
      provide insights into the development of novel potent D3 agonists. We (1)
      identified the chemical features required in effective D3 agonists by
      pharmacophore modeling based upon 18 known diverse D3 agonists; (2) constructed
      the three-dimensional (3D) structure of D3 based on homology modeling and the
      pharmacophore hypothesis; (3) identified the binding modes of the agonists to D3
      by the correlation between the predicted binding free energies and the
      experimental values; and (4) investigated the induced fit of D3 upon agonist
      binding through MD simulations. The pharmacophore models of the D3 agonists and
      the 3D structure of D3 can be used for either ligand- or receptor-based drug
      design. Furthermore, the MD simulations further give the insight that the long
      and flexible EL2 acts as a "door" for agonist binding, and the "ionic lock" at
      the bottom of TM3 and TM6 is essential to transduce the activation signal.

PMID- 20695485
TI  - Phase wave between two oscillators in the photosensitive Belousov-Zhabotinsky
      reaction depending on the difference in the illumination time.
AB  - To investigate the nature of the phase wave between two connected oscillators,
      the photosensitive Belousov-Zhabotinsky (BZ) reaction was examined for two
      connected circular reaction fields, which were drawn by using computer software
      and then projected on a filter paper soaked with BZ solution by using a liquid
      crystal projector. The difference in the time at which illumination was
      terminated between the two circles (Deltat(0)) was changed to control the time at
      which the phase wave was induced. When Deltat(0) was small (0-3 s), the phase
      wave normally propagated on the two circles in one direction. In contrast, when
      Deltat(0) was large (6-10 s), the velocity of the wave decreased near the
      intersection of the two circles. These different features are discussed in
      relation to the excitability of the circles and Deltat(0). The experimental
      results were qualitatively reproduced by a numerical calculation based on the
      modified three-variable Oregonator model that included photosensitivity.

PMID- 20695486
TI  - Genomics and peptidomics of neuropeptides and protein hormones present in the
      parasitic wasp Nasonia vitripennis.
AB  - Neuropeptides and protein hormones constitute a very important group of signaling
      molecules, regulating central physiological processes such as reproduction,
      development, and behavior. Using a bioinformatics approach, we screened the
      recently sequenced genome of the parasitic wasp, Nasonia vitripennis, for the
      presence of these signaling molecules and annotated 30 precursor genes encoding
      51 different mature neuropeptides or protein hormones. Twenty-four of the
      predicted mature Nasonia neuropeptides could be experimentally confirmed by mass
      spectrometry. We also discovered a completely novel neuropeptide gene in Nasonia,
      coding for peptides containing the C-terminal sequence RYamide. This gene has
      orthologs in nearly all arthropods with a sequenced genome, and its expression in
      mosquitoes was confirmed by mass spectrometry. No precursor could be identified
      for N-terminally extended FMRFamides, even though their putative G protein
      coupled receptor (GPCR) is present in the Nasonia genome. Neither the precursor
      nor the putative receptor could be identified for allatostatin-B, capa, the
      glycoprotein hormones GPA2/GPB5, kinin, proctolin, sex peptide, and sulfakinin,
      arguing that these signaling systems are truly absent in the wasp. Also,
      antidiuretic factors, allatotropin, and NPLP-like precursors are missing in
      Nasonia, but here the receptors have not been identified in any insect, so far.
      Nasonia (Hymenoptera) has the lowest number of neuropeptide precursor genes
      compared to Drosophila melanogaster, Aedes aegypti (both Diptera), Bombyx mori
      (Lepidoptera), Tribolium castaneum (Coleoptera), Apis mellifera (Hymenoptera),
      and Acyrthosiphon pisum (Hemiptera). This lower number of neuropeptide genes
      might be related to Nasonia's parasitic life.

PMID- 20695488
TI  - Test MM-PB/SA on true conformational ensembles of protein-ligand complexes.
AB  - The molecular mechanics Poisson-Boltzmann surface area (MM-PB/SA) method has been
      popular for computing protein-ligand binding free energies in recent years. All
      previous evaluations of the MM-PB/SA method are based upon computer-generated
      conformational ensembles, which may be affected by the defective computational
      methods used for preparing these conformational ensembles. In an attempt to reach
      more convincing conclusions, we have evaluated the MM-PB/SA method on a set of 24
      diverse protein-ligand complexes, each of which has a set of conformations
      derived from NMR spectroscopy. Our results indicate that both MM-PB/SA and
      molecular mechanics generalized Born surface area (MM-GB/SA) are able to produce
      a modest correlation between their results and the experimentally measured
      binding free energies on our test set. In particular, both MM-PB/SA and MM-GB/SA
      produced better results by using a representative structure (R = 0.72-0.79)
      rather than averaging over the conformational ensemble of each given complex (R =
      0.61-0.74). A head-to-head comparison with four selected scoring functions (X
      Score, PLP, ChemScore, and DrugScore) on the same test set reveals that MM-PB/SA
      and MM-GB/SA results are marginally better than those produced by scoring
      funcitons, supporting the value of the MM-PB/SA method. Nevertheless, scoring
      functions are still more cost-effective options, especially for high-throughput
      tasks.

PMID- 20695489
TI  - Molecular breeding of tomato lines for mass production of miraculin in a plant
      factory.
AB  - A transgenic tomato line (56B, "Moneymaker") that expresses the miraculin gene
      driven by the CaMV 35S promoter was crossed with a dwarf tomato ("Micro-Tom") for
      the molecular breeding of cultivars that are suitable for miraculin production in
      a closed cultivation system. Plant size, miraculin accumulation, and self-pruning
      growth were used as selection indicators for F2 plants. Two lines were chosen for
      further analysis, bred to the F6 or F7 generation and cultivated in a closed
      cultivation system. In 56B and the two crossed lines, the concentrations of
      miraculin in the pericarp were 140, 367, and 343 microg/g FW, respectively. We
      also estimated that 26.2, 73.6, and 45.9 kg FW/m2 of tomatoes and 2.2, 16.6, and
      9.8 mg/m2 of miraculin in the pericarp, respectively, could be harvested per
      year. These two crossed lines will be useful for the mass production of
      miraculin, especially in a closed cultivation system.

PMID- 20695487
TI  - Proteomics of dense core secretory vesicles reveal distinct protein categories
      for secretion of neuroeffectors for cell-cell communication.
AB  - Regulated secretion of neurotransmitters and neurohumoral factors from dense core
      secretory vesicles provides essential neuroeffectors for cell-cell communication
      in the nervous and endocrine systems. This study provides comprehensive proteomic
      characterization of the categories of proteins in chromaffin dense core secretory
      vesicles that participate in cell-cell communication from the adrenal medulla.
      Proteomic studies were conducted by nano-HPLC Chip MS/MS tandem mass
      spectrometry. Results demonstrate that these secretory vesicles contain proteins
      of distinct functional categories consisting of neuropeptides and neurohumoral
      factors, protease systems, neurotransmitter enzymes and transporters, receptors,
      enzymes for biochemical processes, reduction/oxidation regulation, ATPases,
      protein folding, lipid biochemistry, signal transduction, exocytosis, calcium
      regulation, as well as structural and cell adhesion proteins. The secretory
      vesicle proteomic data identified 371 proteins in the soluble fraction and 384
      membrane proteins, for a total of 686 distinct secretory vesicle proteins.
      Notably, these proteomic analyses illustrate the presence of several neurological
      disease-related proteins in these secretory vesicles, including huntingtin
      interacting protein, cystatin C, ataxin 7, and prion protein. Overall, these
      findings demonstrate that multiple protein categories participate in dense core
      secretory vesicles for production, storage, and secretion of bioactive
      neuroeffectors for cell-cell communication in health and disease.

PMID- 20695490
TI  - Protection of trabecular bone in ovariectomized rats by turmeric (Curcuma longa
      L.) is dependent on extract composition.
AB  - Extracts prepared from turmeric (Curcuma longa L., [Zingiberaceae]) containing
      bioactive phenolic curcuminoids were evaluated for bone-protective effects in a
      hypogonadal rat model of postmenopausal osteoporosis. Three-month female Sprague
      Dawley rats were ovariectomized (OVX) and treated with a chemically complex
      turmeric fraction (41% curcuminoids by weight) or a curcuminoid-enriched turmeric
      fraction (94% curcuminoids by weight), both dosed at 60 mg/kg 3x per week, or
      vehicle alone. Effects of two months of treatment on OVX-induced bone loss were
      followed prospectively by serial assessment of bone mineral density (BMD) of the
      distal femur using dual-energy X-ray absorptiometry (DXA), while treatment
      effects on trabecular bone microarchitecture were assessed at two months by
      microcomputerized tomography (microCT). Chemically complex turmeric did not
      prevent bone loss, however, the curcuminoid-enriched turmeric prevented up to 50%
      of OVX-induced loss of trabecular bone and also preserved the number and
      connectedness of the strut-like trabeculae. These results suggest that turmeric
      may have bone-protective effects but that extract composition is a critical
      factor.

PMID- 20695491
TI  - Kinetic reaction modeling framework for identifying and quantifying reductant
      reactivity in heterogeneous aquifer sediments.
AB  - Water-sediment interactions triggered by the injection of oxidized aqueous
      solutions into anoxic groundwater systems usually modify both the aquifer matrix
      and control the final aqueous composition. The identification and quantification
      of these reactions in complex heterogeneous systems remains a challenge for the
      analysis and prediction of water quality changes. Driven by the proposed
      injection of large quantities of oxic water into a deep anoxic heterogeneous
      pyritic aquifer; this study was undertaken to quantify the reactivity of aquifer
      sediments with respect to oxidant consumption and to characterize the variability
      of the reaction rates across different lithological units. A total of 53 samples
      were incubated for periods of 14, 37, and 50 days, during which the gas-phase was
      continuously monitored and the aqueous composition analyzed. A geochemical
      modeling framework was developed that incorporated a mixed set of equilibrium and
      kinetic reactions and supported the interpretation and quantification of the
      geochemical controls. The good agreement between simulated and experimental
      results of O2 consumption, CO2 production, pH, major ions, and trace metals
      suggests that the framework was able to successfully quantify reaction rates of
      competing redox and buffering reactions for the different lithological aquifer
      material.

PMID- 20695492
TI  - Fenton activity and cytotoxicity studies of iron-loaded carbon particles.
AB  - The chemical and biological properties of iron-loaded manufactured carbon
      nanoparticles (Flammruss 101) were contrasted with those of an iron-loaded
      synthetic carbon particle. X-ray photoelectron spectroscopy was used to
      characterize the iron on the carbon particles. Production of hydroxyl free
      radicals via the Fenton reaction was monitored by electron paramagnetic resonance
      spectroscopy. The iron-loaded synthetic carbon particles produced a positive
      Fenton response, whereas the iron-loaded manufactured carbon particles did not.
      The source of the Fenton activity of the synthetic carbon particles is proposed
      to be a soluble iron compound that was formed during the synthesis of the
      particle. A likely candidate for the soluble iron species is Fe2F5, which was
      synthesized and its properties were examined. Higher toxicity of Fe2F5 toward
      murine macrophages compared with other simple iron salts was attributed to
      soluble iron that was stabilized by the fluoride ligand. The cytotoxicity of
      manufactured carbon particles toward murine macrophages decreased or remained
      unaltered upon impregnation with iron compounds.

PMID- 20695493
TI  - Dinuclear gold diselenophosphate complexes: structures and photoluminescence.
AB  - Structures of [AuSe(2)P(OR)(2)](2) (R = (i)Pr, 1; Et, 2), the first homoleptic
      dinuclear gold(I) bridged by phosphorodiselenoates, are reported along with their
      intriguing photoluminescent properties, which display multiple emissions as well
      as thermochromism.

PMID- 20695494
TI  - Conjugated polymer nanoparticles for drug delivery and imaging.
AB  - We prepared a new conjugated polymer nanoparticle with the size of about 50 nm
      that is prepared by electrostatic assembly of cationic conjugated polymer PFO and
      anionic poly(l-glutamic acid) conjugated with anticancer drug doxorubicin (PFO/PG
      Dox). The PFO exhibits good fluorescence quantum yield, photostability, and
      little cytotoxicity to meet the essential requests for cell imaging. In PFO/PG
      Dox nanoparticles, the fluorescence of PFO is highly quenched by Dox by electron
      transfer mechanism, and thus the PFO is in the fluorescence "turn-off' state.
      After PFO/PG-Dox nanoparticles are exposed to carboxypeptidase or are taken up by
      cancer cells, the poly(l-glutamic acid) is hydrolysed to release the Dox,
      inducing the activation of PFO fluorescence to "turn-on" state. This
      multifunctional nanoparticle system can deliver Dox to targeted cancer cells and
      monitor the Dox release based on fluorescence "turn-on" signal of PFO, which
      concurrently images the cancer cells. The present work opens the door for new
      functional studies of conjugated polymer in simultaneous imaging and disease
      therapeutics.

PMID- 20695495
TI  - PNIPAAm-grafted-collagen as an injectable, in situ gelling, bioactive cell
      delivery scaffold.
AB  - We synthesized two thermoresponsive, bioactive cell scaffolds by decorating the
      backbone of type I bovine collagen with linear chains of poly(N
      isopropylacrylamide) (PNIPAAm), with the ultimate aim of providing facile
      delivery via injection and support of retinal pigment epithelial (RPE) cells into
      the back of the eye for the treatment of retinal degenerative diseases. Both
      scaffolds displayed rapid, subphysiological phase transition temperatures and
      were capable of noninvasively delivering a liquid suspension of cells that gels
      in situ forming a cell-loaded scaffold, theoretically isolating treatment to the
      injection site. RPE cells demonstrated excellent viability when cultured with the
      scaffolds, and expulsion of cells arising from temperature-induced PNIPAAm chain
      collapse was overcome by incorporating a room-temperature incubation period prior
      to scaffold phase transition. These results indicate the potential of using
      PNIPAAm-grafted-collagen as a vehicle for the delivery of therapeutic cells to
      the subretinal space.

PMID- 20695496
TI  - Thermodynamic origin of selective binding of beta-cyclodextrin derivatives with
      chiral chromophoric substituents toward steroids.
AB  - Two beta-cyclodextrin derivatives with chiral chromophoric substituents, that is,
      L- (1) and D-tyrosine-modified beta-cyclodextrin (2), were synthesized and fully
      characterized. Their inclusion modes, binding abilities, and molecular
      selectivities with four steroid guests, that is, cholic acid sodium salt (CA),
      deoxycholic acid sodium salt (DCA), glycochoic acid sodium salt (GCA), and
      taurocholic acid sodium salt (TCA), were investigated by the circular dichroism,
      2D NMR, and isothermal titration microcalorimetry (ITC). The results obtained
      from the circular dichroism and 2D NMR showed that two hosts adopted the
      different binding geometry, and these differences subsequently resulted in the
      significant differences of molecular binding abilities and selectivities. As
      compared with native beta-cyclodextrin and tryptophan-modified beta-cyclodextrin,
      host 2 showed the enhanced binding abilities for CA and DCA but the decreased
      binding abilities for GCA and TCA; however, host 1 showed the decreased binding
      abilities for all four bile salts. The best guest selectivity and the best host
      selectivity were K(S)(2-DCA)/K(S)(2-TCA) = 12.6 and K(S)(2-CA)/K(S)(1-CA) = 10,
      respectively, both exhibiting great enhancement as compared with the
      corresponding values of the previously reported L- and D-tryptophan-modified beta
      cyclodextrins. Thermodynamically, it was the favorable enthalpic gain that led to
      the high guest selectivity and host selectivity.

PMID- 20695497
TI  - Origin of the commonly observed secondary relaxation process in saccharides.
AB  - Broadband dielectric relaxation studies were performed on D-glucose and 1,6
      anhydro-D-glucose. In the liquid phase of both systems, one can observe the
      cluster relaxation and structural relaxation. In the glassy state of D-glucose
      two secondary relaxations were recorded. The slower one, hardly detectable in the
      loss spectra, was identified as the Johari-Goldstein type (JG) relaxation. The
      faster one, the gamma-relaxation, is visible as a well pronounced peak. For the
      past few years the origin of this process has been a subject of hot debate.
      Different authors have speculated about the source of this relaxation, but no
      consensus was reached. Moreover, application of more sophisticated method, such
      as NMR and MD simulations have not resolved this problem yet. Comparison of the
      dielectric loss spectra measured for D-glucose and 1,6-anhydro-D-glucose,
      combined with other experimental findings described in detail in this paper,
      enabled us to certify unquestionably, that the rotation of hydroxymethyl group is
      the origin of gamma-relaxation in D-glucose as well as in the whole family of
      saccharides. Additionally, calculations of conformational changes with use of
      density functional theory (DFT) were performed to support our identification.

PMID- 20695499
TI  - Interconnected trimeric, pentameric, and hexameric metallacycles in a singular
      silver-adenine framework.
AB  - This Article describes the synthesis and crystallographic investigation of a
      silver complex of a modified adenine derivative bearing a nitrile pendant at the
      N9 position. All three adenine ring nitrogen atoms coordinated to silver ions,
      while the fourth coordination was achieved at the nitrile functionality, thus
      resulting in the formation of silver-mediated interconnected trimeric,
      pentameric, and hexameric metallacyclic rings and helical signatures in two
      orthogonal directions.

PMID- 20695500
TI  - Protonation of a hydroxide anion bridging two divalent magnesium cations in water
      probed by first-principles metadynamics simulation.
AB  - The protonation of a hydroxide anion (OH(-)) located between two magnesium
      cations (Mg(2+)) in aqueous solution has been investigated by first-principles
      metadynamics simulation. We observe that the complex Mg(2+)-OH(-)-Mg(2+) is
      stabilized by the coparticipation of the hydroxide anion to the first hydration
      shells of both the Mg(2+) cations. Contrary to the cases of OH(-) in pure water,
      the transfer of protons in the presence of the divalent metal ions turns out to
      be a slow chemical event. This can be ascribed to the decreased proton affinity
      of the bridging OH(-). Metadynamics simulation, used to overcome the difficulty
      of the long time scale required by the protonation of the bridging OH(-), has
      shown that the system possesses a great stability on the reactant state,
      characterized by a bioctahedral (6,6) solvation structure around the two Mg(2+)
      cations. The exploration of the free energy landscape shows that this stable
      bioctahedral configuration converts into a lower coordinated (5,6) structure,
      leading to a proton transfer from a water molecule belonging to the first
      solvation shell of the Mg(2+) ion having the lower coordination to the bridging
      OH(-); the free energy barrier for the protonation reaction is 11 kcal/mol,
      meaning that the bridging hydroxide is a weak base. During the proton transfer,
      the bridging OH(-) reverts to an H(2)O molecule, and this breaks the
      electrostatic coupling of the two Mg(2+) ions, which depart independently with
      their own hydration shells, one of which is entirely formed by water molecules.
      The second one carries the newly created OH(-). Our results show that the
      flexibility in the metal coordination plays a crucial role in both the
      protonation process of the bridging OH(-) and the separation of the metal
      cations, providing useful insight into the nature of proton transfer in binuclear
      divalent metal ions, with several biological implications, such as, for instance,
      transesterification of catalytic RNA.

PMID- 20695498
TI  - Characterization of glycosyltransferase DesVII and its auxiliary partner protein
      DesVIII in the methymycin/picromycin biosynthetic pathway.
AB  - The in vitro characterization of the catalytic activity of DesVII, the
      glycosyltransferase involved in the biosynthesis of the macrolide antibiotics
      methymycin, neomethymycin, narbomycin, and pikromycin in Streptomyces venezuelae,
      is described. DesVII is unique among glycosyltransferases in that it requires an
      additional protein component, DesVIII, for activity. Characterization of the
      metabolites produced by a S. venezuelae mutant lacking the desVIII gene confirmed
      that desVIII is important for the biosynthesis of glycosylated macrolides but can
      be replaced by at least one of the homologous genes from other pathways. The
      addition of recombinant DesVIII protein significantly improves the glycosylation
      efficiency of DesVII in the in vitro assay. When affinity-tagged DesVII and
      DesVIII proteins were coproduced in Escherichia coli, they formed a tight
      (alphabeta)(3) complex that is at least 10(3)-fold more active than DesVII alone.
      The formation of the DesVII/DesVIII complex requires coexpression of both genes
      in vivo and cannot be fully achieved by mixing the individual protein components
      in vitro. The ability of the DesVII/DesVIII system to catalyze the reverse
      reaction with the formation of TDP-desosamine was also demonstrated in a
      transglycosylation experiment. Taken together, our data suggest that DesVIII
      assists the folding of DesVII during protein production and remains tightly bound
      during catalysis. This requirement must be taken into consideration in the design
      of combinatorial biosynthetic experiments with new glycosylated macrolides.

PMID- 20695501
TI  - Identification of HSP60 as a primary target of o-carboranylphenoxyacetanilide, an
      HIF-1alpha inhibitor.
AB  - We succeeded in the design and synthesis of multifunctional chemical probes of
      the HIF-1alpha inhibitor carboranylphenoxyacetanilide (1) that combine
      photoaffinity labeling and click reaction to identify the target protein. HSP60
      was identified as a primary target protein of 1 using the chemical probes 2 and
      3. Furthermore, HSP60 inhibitor 4 suppressed hypoxia-induced HIF activation,
      indicating that HSP60 affects HIF-1alpha accumulation directly or indirectly.

PMID- 20695502
TI  - Electrical double-layer capacitance in room temperature ionic liquids: ion-size
      and specific adsorption effects.
AB  - The electrical double-layer structure and capacitance in room temperature ionic
      liquids at electrified interfaces were systematically studied with use of the
      self-consistent mean-field theory. The capacitance curve departs from symmetry
      with respect to the point of zero charge when unequal ion-size is implemented or
      when specific adsorption of ions is introduced. For the case of unequal ion-size,
      the shape of the capacitance curve is strongly determined by the size of the
      counterion and only weakly influenced by the co-ion size. When present,
      specifically adsorbed ions would change the capacitance within a limited range of
      applied potential from the point of zero charge, which itself varies with the
      strength of specific adsorption.

PMID- 20695503
TI  - Cyclobutane-derived diamines: synthesis and molecular structure.
AB  - Cyclobutane diamines (i.e., cis- and trans-1,3-diaminocyclobutane, 6-amino-3
      azaspiro[3.3]heptane, and 3,6-diaminospiro[3.3]heptane) are considered as
      promising sterically constrained diamine building blocks for drug discovery. An
      approach to the syntheses of their Boc-monoprotected derivatives has been
      developed aimed at the preparation of multigram amounts of the compounds. These
      novel synthetic schemes exploit classical malonate alkylation chemistry for the
      construction of cyclobutane rings. The conformational preferences of the
      cyclobutane diamine derivatives have been evaluated by X-ray diffraction and
      compared with the literature data on sterically constrained diamines, which are
      among the constituents of commercially available drugs.

PMID- 20695504
TI  - Cell-selective lysis by novel analogues of melittin against human red blood cells
      and Escherichia coli.
AB  - Melittin is a good model antimicrobial peptide to understand the basis of its
      lytic activities against bacteria and mammalian cells. Novel analogues of
      melittin were designed by substituting the leucine residue(s) at the "d" and "a"
      positions of its previously identified leucine zipper motif. A scrambled peptide
      having the same composition of melittin with altered leucine zipper sequence was
      also designed. The analogues of melittin including the scrambled peptide showed a
      drastic reduction in cytotoxicity though they exhibited comparable bactericidal
      activities. Only melittin but not its analogues localized strongly onto hRBCs and
      formed pores of approximately 2.2-3.4 nm. However, melittin and its analogues
      localized similarly onto Escherichia coli and formed pores of varying sizes as
      tested onto Bacillus megaterium. The data showed that the substitution of
      hydrophobic leucine residue(s) by lesser hydrophobic alanine residue(s) in the
      leucine zipper sequence of melittin disturbed its pore-forming activity and
      mechanism only in hRBCs but not in the tested bacteria.

PMID- 20695506
TI  - Combining function.

PMID- 20695508
TI  - Comment on "Single-file diffusion of confined water inside SWNTs: an NMR study".

PMID- 20695510
TI  - NaNaX 4--4th event of the international conference series "Nanoscience with
      Nanocrystals".
AB  - The conference "NaNaX 4--Nanoscience with Nanocrystals" held near Munich (April
      11-15, 2010) brought together a wide range of scientists discussing the most
      important current issues in the field of colloidal nanoparticles. Chemical
      synthesis gives access to nanocrystals of controlled size, shape, composition,
      and surface functionalization. Past research mainly concentrated on cadmium and
      lead chalcogenide nanocrystals as well as on gold and iron oxide nanoparticles.
      Today, there is a trend toward the development of nanoscale heterostructures,
      which combine different classes of materials and exhibit unique optical,
      magnetic, and electronic properties. Beside their interest for fundamental
      science, colloidal nanoparticles hold great promise for a wide range of
      applications. To this end, speakers and poster presenters showed routes for
      designing and using nanocrystals in biological imaging and sensing, in energy
      related applications, and in catalysis. This report gives a nonexhaustive
      overview of selected "hot topics" in nanoparticle research discussed at NaNaX 4.

PMID- 20695511
TI  - Nanoporous membranes derived from block copolymers: from drug delivery to water
      filtration.
AB  - With nanoscale pores, high porosity, narrow pore size distributions, and tunable
      chemical and mechanical properties, block copolymers hold tremendous potential as
      robust, efficient, and highly selective separation membranes. Recent work by Yang
      et al. illustrates how block copolymers can be employed in the preparation of
      membranes for use in controlled, long-term, protein-delivery devices. Their work
      demonstrates that highly efficient and tunable separations are possible with
      block copolymer membranes. Although significant progress over the past 10 years
      has advanced the quality, efficacy, and applicability of such membranes, more
      work is required before benefits are realized for other demanding applications
      such as water purification.

PMID- 20695512
TI  - Nanofabrication at high throughput and low cost.
AB  - The task of nanofabrication can, in principle, be divided into two separate
      tracks: generation and replication of the patterned features. These two tracks
      are different in terms of characteristics, requirements, and aspects of emphasis.
      In general, generation of patterns is commonly achieved in a serial fashion using
      techniques that are typically slow, making this process only practical for making
      a small number of copies. Only when combined with a rapid duplication technique
      will fabrication at high-throughput and low-cost become feasible. Nanoskiving is
      unique in that it can be used for both generation and duplication of patterned
      nanostructures.

PMID- 20695513
TI  - Nanomaterials in the construction industry: a review of their applications and
      environmental health and safety considerations.
AB  - The extraordinary chemical and physical properties of materials at the nanometer
      scale enable novel applications ranging from structural strength enhancement and
      energy conservation to antimicrobial properties and self-cleaning surfaces.
      Consequently, manufactured nanomaterials (MNMs) and nanocomposites are being
      considered for various uses in the construction and related infrastructure
      industries. To achieve environmentally responsible nanotechnology in
      construction, it is important to consider the lifecycle impacts of MNMs on the
      health of construction workers and dwellers, as well as unintended environmental
      effects at all stages of manufacturing, construction, use, demolition, and
      disposal. Here, we review state-of-the-art applications of MNMs that improve
      conventional construction materials, suggest likely environmental release
      scenarios, and summarize potential adverse biological and toxicological effects
      and their mitigation. Aligned with multidisciplinary assessment of the
      environmental implications of emerging technologies, this review seeks to promote
      awareness of potential benefits of MNMs in construction and stimulate the
      development of guidelines to regulate their use and disposal to mitigate
      potential adverse effects on human and environmental health.

PMID- 20695514
TI  - Chemical doping of large-area stacked graphene films for use as transparent,
      conducting electrodes.
AB  - Graphene is considered a leading candidate to replace conventional transparent
      conducting electrodes because of its high transparency and exceptional transport
      properties. The effect of chemical p-type doping on graphene stacks was studied
      in order to reduce the sheet resistance of graphene films to values approaching
      those of conventional transparent conducting oxides. In this report, we show that
      large-area, stacked graphene films are effectively p-doped with nitric acid. The
      doping decreases the sheet resistance by a factor of 3, yielding films comprising
      eight stacked layers with a sheet resistance of 90 Omega/(square) at a
      transmittance of 80%. The films were doped either after all of the layers were
      stacked (last-layer-doped) or after each layer was added (interlayer-doped). A
      theoretical model that accurately describes the stacked graphene film system as a
      resistor network was developed. The model defines a characteristic transfer
      length where all the channels in the graphene films actively contribute to
      electrical transport. The experimental data shows a linear increase in
      conductivity with the number of graphene layers, indicating that each layer
      provides an additional transport channel, in good agreement with the theoretical
      model.

PMID- 20695515
TI  - Nanosieving of anions and cavity-size-dependent association of cyclodextrins on a
      1-adamantanethiol self-assembled monolayer.
AB  - In this paper, we studied charge transfer through a self-assembled monolayer
      (SAM) of 1-adamantanethiol on gold. Charge transfer through the 1-adamantanethiol
      SAM depended on the type of anion present when [Fe(CN)6]3- was used as a redox
      probe. The sluggish charge transfer process was monitored by cyclic voltammetry
      using the relatively large and hydrophobic perchlorate and hexafluorophosphate
      ions as the supporting electrolyte. In contrast, the charge transfer kinetics
      were nearly identical to those measured on bare gold with chloride, sulfate, and
      nitrate ions as the supporting electrolyte. We investigated the adsorption of
      alpha- and beta-cyclodextrin on the 1-adamantanethiol SAM via a host-guest
      interaction. The 1-adamantanethiol SAM could not bind beta-cyclodextrin via a
      host-guest interaction, probably due to the proximity of neighboring adamantine
      molecules on the surface. Immobilization of alpha-cyclodextrin by formation of an
      exterior complex with the SAM suppressed charge transfer. The adsorbed alpha
      cyclodextrin was quantified using faradaic impedance experiments. The obtained
      adsorption isotherm was in good agreement with the Langmuir isotherm with a
      binding constant of 39.53 M(-1).

PMID- 20695516
TI  - Elastic distortions of carbon nanotubes induced by chiral fullerene chains.
AB  - We show that when Y@C82 metallofullerenes are inserted into single-walled carbon
      nanotubes (SWNTs) with large diameters of 2 nm, the minimum energy configuration
      is a double-helix chiral structure extending over hundreds of nanometers. We
      demonstrate rotation of the double-helix fullerene chain within the nanotube host
      that induces real time elastic distortions of the nanotube in a crank-shaft
      manner. Molecular dynamics simulations, employing an atomic description of the
      confining SWNT and a reduced description of Y@C82, reproduce the key experimental
      observations.

PMID- 20695517
TI  - Damaging graphene with ozone treatment: a chemically tunable metal-insulator
      transition.
AB  - We present a multiscale ab initio study of electronic and transport properties of
      two-dimensional graphene after epoxide functionalization via ozone treatment. The
      orbital rehybridization induced by the epoxide groups triggers a strong
      intervalley scattering and changes dramatically the conduction properties of
      graphene. By varying the coverage density of epoxide defects from 0.1 to 4%,
      charge conduction can be tuned from a diffusive to a strongly localized regime,
      with localization lengths down to a few nanometers long. Experimental results
      supporting the interpretation as a metal-insulator transition are also provided.

PMID- 20695518
TI  - Topological transitions in carbon nanotube networks via nanoscale confinement.
AB  - Efforts aimed at large-scale integration of nanoelectronic devices that exploit
      the superior electronic and mechanical properties of single-walled carbon
      nanotubes (SWCNTs) remain limited by the difficulties associated with
      manipulation and packaging of individual SWNTs. Alternative approaches based on
      ultrathin carbon nanotube networks (CNNs) have enjoyed success of late with the
      realization of several scalable device applications. However, precise control
      over the network electronic transport is challenging due to (i) an often
      uncontrollable interplay between network coverage and its detailed topology and
      (ii) the inherent electrical heterogeneity of the constituent SWNTs. In this
      article, we use template-assisted fluidic assembly of SWCNT networks to explore
      the effect of geometric confinement on the network topology. Heterogeneous SWCNT
      networks dip-coated onto submicrometer wide ultrathin polymer channels become
      increasingly aligned with decreasing channel width and thickness. Experimental
      scale coarse-grained computations of interacting SWCNTs show that the effect is a
      reflection of a topology that is no longer dependent on the network density,
      which in turn emerges as a robust knob that can induce semiconductor-to-metallic
      transitions in the network response. Our study demonstrates the effectiveness of
      directed assembly on channels with varying degrees of confinement as a simple
      tool to tailor the conductance of the otherwise heterogeneous network, opening up
      the possibility of robust large-scale CNN-based devices.

PMID- 20695521
TI  - Enhanced generation of cytotoxic T lymphocytes by heat shock protein 70 fusion
      proteins harboring both CD8(+) T cell and CD4(+) T cell epitopes.
AB  - Heat shock protein 70 (Hsp70) can be a potent carrier of antigens because it is
      effectively delivered to antigen presenting cells (APCs) and activates innate
      immunity. To induce a potent cytotoxic T lymphocyte (CTL) response, a Hsp70
      fusion protein harboring both CD8(+) and CD4(+) T cell epitopes was developed
      based on the recent understanding of the importance of the role of CD4(+) T cells
      in inducing the CTL response following vaccination. OVA(257-264) (pepI) and
      OVA(323-339) (pepII) were selected as the CD8(+) and CD4(+) T cell epitope of a
      model antigen, ovalbumin (OVA), respectively. Hsp70 and its fusion proteins,
      Hsp70-pepI, pepII-Hsp70, Hsp70-pepII and pepII-Hsp70-pepI, were developed. pepII
      Hsp70 and pepII-Hsp70-pepI were effectively presented on MHC class II of
      macrophages compared with Hsp70-pepII, suggesting that pepII conjugation to the N
      terminus of Hsp70 is better than the C-terminus for more effective MHC class II
      antigen presentation. Immunization with pepII-Hsp70-pepI resulted in a higher CTL
      activity than immunization with the mixture of Hsp70-pepI and pepII-Hsp70.
      Furthermore, pepII-Hsp70-pepI exhibited a greater antitumor effect in the mice
      bearing EG7 tumor cells than the physical mixture of Hsp70-pepI and pepII-Hsp70.
      In addition, immunization with the DCs pulsed with the fusion proteins also
      suggested that APCs which present both pepI and pepII can induce the highest CTL
      generation. These results demonstrated that Hsp70 fusion protein harboring both
      pepI and pepII is a useful option for Hsp70-based antigen delivery systems.

PMID- 20695522
TI  - Crystal structures of anaplastic lymphoma kinase in complex with ATP competitive
      inhibitors.
AB  - Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase involved in the
      development of several human cancers and, as a result, is a recognized target for
      the development of small-molecule inhibitors for the treatment of ALK-positive
      malignancies. Here, we present the crystal structures of the unphosphorylated
      human ALK kinase domain in complex with the ATP competitive ligands PHA-E429 and
      NVP-TAE684. Analysis of these structures provides valuable information concerning
      the specific characteristics of the ALK active site as well as giving indications
      about how to obtain selective ALK inhibitors. In addition, the ALK-KD-PHA-E429
      structure led to the identification of a potential regulatory mechanism involving
      a link made between a short helical segment immediately following the DFG motif
      and an N-terminal two-stranded beta-sheet. Finally, mapping of the activating
      mutations associated with neuroblastoma onto our structures may explain the roles
      these residues have in the activation process.

PMID- 20695524
TI  - A solution model of the complex formed by adrenodoxin and adrenodoxin reductase
      determined by paramagnetic NMR spectroscopy.
AB  - Lanthanide tags offer the opportunity to retrieve long-range distance information
      from NMR experiments that can be used to guide protein docking. To determine
      whether sufficient restraints can be retrieved for proteins with low solubility
      and availability, Ln tags were applied in the study of the 65 kDa membrane
      associated protein complex formed by the electron carrier adrenodoxin and its
      electron donor, adrenodoxin reductase. The reductase is only monomeric at low
      concentration, and the paramagnetic iron-sulfur cluster of adrenodoxin broadens
      many of the resonances of nuclei in the interface. Guided by the paramagnetic
      restraints obtained using two Ln-tag attachment sites, protein docking yields a
      cluster of solutions with an rmsd of 3.2 A. The mean structure is close to the
      crystal structure of the cross-linked complex, with an rmsd of 4.0 A. It is
      concluded that with the application of Ln tags paramagnetic NMR restraints for
      structure determination can be retrieved even for difficult, low-concentration
      protein complexes.

PMID- 20695523
TI  - AGG interruptions in (CGG)(n) DNA repeat tracts modulate the structure and
      thermodynamics of non-B conformations in vitro.
AB  - The trinucleotide repeat sequence CGG/CCG is known to expand in the human genome.
      This expansion is the primary pathogenic signature of fragile X syndrome, which
      is the most common form of inherited mental retardation. It has been proposed
      that formation of non-B conformations by the repetitive sequence contributes to
      the expansion mechanism. It is also known that the CGG/CCG repeat sequence of
      healthy individuals, which is not prone to expansion, contains AGG/CCT
      interruptions every 8-11 CGG/CCG repeats. Using DNA containing 19 or 39 CGG
      repeats, we have found that both the position and number of interruptions
      modulate the non-B conformation adopted by the repeat sequence. Analysis by
      chemical probes revealed larger loops and the presence of bulges for sequences
      containing interruptions. Additionally, using optical analysis and calorimetry,
      the effect of these structural changes on the thermodynamic stability of the
      conformation has been quantified. Notably, changing even one nucleotide, as
      occurs when CGG is replaced with an AGG interruption, causes a measurable
      decrease in the stability of the conformation adopted by the repeat sequence.
      These results provide insight into the role interruptions may play in preventing
      expansion in vivo and also contribute to our understanding of the relationship
      between non-B conformations and trinucleotide repeat expansion.

PMID- 20695525
TI  - Polar groups in membrane channels: consequences of replacing alanines with
      serines in membrane-spanning gramicidin channels.
AB  - To explore the consequences of burying polar, hydrogen-bonding hydroxyl groups
      within the hydrocarbon core of lipid bilayer membranes, we examined the
      structural and functional effects of alanine-to-serine substitutions in bilayer
      spanning gramicidin channels. A native Ala was replaced by Ser at position 3 or 5
      in the gramicidin A (gA) sequence: formyl-VG(2)A(3)LA(5)VVVWLWLWLW-ethanolamide
      (d-residues underlined). In the head-to-head dimers that form the conducting,
      membrane-spanning gA channels, these sequence positions are located near the
      lipid bilayer center (and subunit interface). The sequence substitutions at
      positions 3 and 5 were tested within the context of having either Gly or d-Ala at
      position 2, because d-Ala(2) causes the channel lifetimes to increase 3-fold
      relative to Gly(2) [Mattice et al. (1995) Biochemistry 34, 6827]. Size-exclusion
      chromatograms and circular dichroism spectra show that the Ala --> Ser
      replacements are well tolerated and have little effect on channel structure. In
      planar bilayers, the Ser-substituted gramicidins form well-defined channels, with
      cation conductances that are approximately 60% of those of the reference
      channels. The Ser-substituted channels are structurally equivalent to native
      gramicidin channels, as demonstrated by the formation of heterodimeric channels
      between a Ser-containing subunit and a native gramicidin subunit. These hybrid
      channels exhibit rectification, attributable to asymmetric placement of the
      single Ser hydroxyl group with respect to the bilayer center. Compared to the
      corresponding Ala-containing reference channels, the polar Ser residues decrease
      the analogues' channel-forming potency by 3 orders of magnitude, indicating a
      substantial energetic penalty ( approximately 15 kJ/mol) for burying the polar
      Ser side chain in the bilayer hydrophobic core.

PMID- 20695526
TI  - Electron paramagnetic resonance studies of functionally active, nitroxide spin
      labeled peptide analogues of the C-terminus of a G-protein alpha subunit.
AB  - The C-terminal tail of the transducin alpha subunit, Gtalpha(340-350), is known
      to bind and stabilize the active conformation of rhodopsin upon photoactivation
      (R*). Five spin-labeled analogues of Gtalpha(340-350) demonstrated native-like
      activity in their ability to bind and stabilize R*. The spin-label 2,2,6,6
      tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid (TOAC) was employed at
      interior sites within the peptide, whereas a Proxyl (3-carboxyl-2,2,5,5
      tetramethyl-pyrrolidinyloxy) spin-label was employed at the amino terminus of the
      peptide. Upon binding to R*, the electron paramagnetic resonance spectrum of
      TOAC(343)-Gtalpha(340-350) revealed greater immobilization of the nitroxide when
      compared to that of the N-terminally modified Proxyl-Gtalpha(340-350) analogue. A
      doubly labeled Proxyl/TOAC(348)-Gtalpha(340-350) was examined by DEER spectrocopy
      to determine the distribution of distances between the two nitroxides in the
      peptides when in solution and when bound to R*. TOAC and Proxyl spin-labels in
      this GPCR-G-protein alpha-peptide system provide unique biophysical probes that
      can be used to explore the structure and conformational changes at the rhodopsin
      G-protein interface.

PMID- 20695528
TI  - Modulation of the oligomerization of myelin proteolipid protein by transmembrane
      helix interaction motifs.
AB  - Proteolipid protein (PLP) is a highly hydrophobic 276-residue integral membrane
      protein that constitutes more than 50% of the total protein in central nervous
      system myelin. Previous studies have shown that this protein exists in myelin as
      an oligomer rather than as a monomer, and mutations in PLP that lead to
      neurological disorders such as Pelizaeus-Merzbacher disease and spastic
      paraplegia type 2 have been reported to affect its normal oligomerization. Here
      we employ peptide-based and in vivo approaches to examine the role of the TM
      domain in the formation of PLP quaternary structure through homo-oligomeric helix
      helix interactions. Focusing on the TM4 alpha-helix (sequence
      (239)FIAAFVGAAATLVSLLTFMIAATY(262)), the site of several disease-causing point
      mutations that involve putative small residue helix-helix interaction motifs in
      the TM4 sequence, we used SDS-PAGE, fluorescence resonance energy transfer, size
      exclusion chromatography, and TOXCAT assays in an Escherichia coli membrane to
      show that the PLP TM4 helix readily assembles into varying oligomeric states. In
      addition, through targeted studies of the PLP TM4 alpha-helix with point
      mutations that selectively eliminate these small residue motifs via substitution
      of Gly, Ala, or Ser residues with Ile residues, we describe a potential mechanism
      through which disease-causing point mutations can lead to aberrant PLP assembly.
      The overall results suggest that TM segments in misfolded PLP monomers that
      expose and/or create surface-exposed helix-helix interaction sites that are
      normally masked may have consequences for disease.

PMID- 20695527
TI  - Reversible post-translational carboxylation modulates the enzymatic activity of N
      acetyl-L-ornithine transcarbamylase.
AB  - N-Acetyl-l-ornithine transcarbamylase (AOTCase), rather than ornithine
      transcarbamylase (OTCase), is the essential carbamylase enzyme in the arginine
      biosynthesis of several plant and human pathogens. The specificity of this unique
      enzyme provides a potential target for controlling the spread of these pathogens.
      Recently, several crystal structures of AOTCase from Xanthomonas campestris (xc)
      have been determined. In these structures, an unexplained electron density at the
      tip of the Lys302 side chain was observed. Using (13)C NMR spectroscopy, we show
      herein that Lys302 is post-translationally carboxylated. The structure of wild
      type AOTCase in a complex with the bisubstrate analogue N(delta)
      (phosphonoacetyl)-N(alpha)-acetyl-l-ornithine (PALAO) indicates that the carboxyl
      group on Lys302 forms a strong hydrogen bonding network with surrounding active
      site residues, Lys252, Ser253, His293, and Glu92 from the adjacent subunit either
      directly or via a water molecule. Furthermore, the carboxyl group is involved in
      binding N-acetyl-l-ornithine via a water molecule. Activity assays with the wild
      type enzyme and several mutants demonstrate that the post-translational
      modification of lysine 302 has an important role in catalysis.

PMID- 20695529
TI  - Investigation of stability and disulfide bond shuffling of lipid transfer
      proteins by molecular dynamics simulation.
AB  - Proteins comprising each of the two plant nonspecific lipid transfer protein
      (LTP) families, LTP1s and LTP2s, share similar folds and biological functions and
      are stabilized by four native disulfide bonds. Disulfide-scrambling experiments
      suggested that rice LTP2 is more thermostable than rice LTP1 and identified
      multiple disulfide-scrambled isomers for LTP1 but only one for LTP2. According to
      the potential energy evaluated in two GROMOS force fields, however, rice LTP1 is
      more stable than either rice or wheat LTP2. Moreover, the published rice LTP2 NMR
      model structure is found to be highly unfavorable. The reasons for this are
      investigated, and it is found that the rice LTP2 sequence is in fact more
      compatible with the more ordered X-ray structure of wheat LTP2 than with the
      published rice LTP2 NMR model structure. The proposed disulfide bond shuffling of
      rice LTP1, rice LTP2, and, for comparative purposes, wheat LTP2 and a homology
      model combining the rice LTP2 sequence with the wheat LTP2 structure is then
      investigated with a computational disulfide-scrambling technique.

PMID- 20695530
TI  - Chemical basis for the selectivity of the von Hippel Lindau tumor suppressor pVHL
      for prolyl-hydroxylated HIF-1alpha.
AB  - In animals, the post-translational hydroxylation of hypoxia inducible factor
      (HIF) is a central mechanism for regulating gene expression in an oxygen
      dependent manner. The oxygenase-catalyzed trans-4-prolyl hydroxylation of HIF
      alpha increases its affinity for the von Hippel Lindau protein elongin B/C (VCB)
      ubiquitin ligase complex, leading to HIF-alpha degradation. The level of binding
      of HIF-alpha to VCB is increased by approximately 1000-fold upon addition of a
      single oxygen atom to a conserved proline residue. Here, we describe
      computational studies on the chemical basis of this "switchlike" signaling event.
      The results support crystallographic analyses showing the importance of hydrogen
      bonding in the binding of hydroxylated HIF-alpha to VCB and suggest that trans 4
      hydroxylation "preorganizes" the proline residue to adopt the C(4)-exo
      conformation, via operation of the stereoelectronic gauche effect.

PMID- 20695531
TI  - The three-his triad in Dke1: comparisons to the classical facial triad.
AB  - The oxygen activating mononuclear non-heme ferrous enzymes catalyze a diverse
      range of chemistry yet typically maintain a common structural motif: two
      histidines and a carboxylate coordinating the iron center in a facial triad. A
      new Fe(II) coordinating triad has been observed in two enzymes, diketone-cleaving
      dioxygenase, Dke1, and cysteine dioxygenase (CDO), and is composed of three
      histidine residues. The effect of this three-His motif in Dke1 on the geometric
      and electronic structure of the Fe(II) center is explored via a combination of
      absorption, CD, MCD, and VTVH MCD spectroscopies and DFT calculations. This
      geometric and electronic structure of the three-His triad is compared to that of
      the classical (2-His-1-carboxylate) facial triad in the alpha-ketoglutarate
      (alphaKG)-dependent dioxygenases clavaminate synthase 2 (CS2) and
      hydroxyphenylpyruvate dioxygenase (HPPD). Comparison of the ligand fields at the
      Fe(II) shows little difference between the three-His and 2-His-1-carboxylate
      facial triad sites. Acetylacetone, the substrate for Dke1, will also bind to HPPD
      and is identified as a strong donor, similar to alphaKG. The major difference
      between the three-His and 2-His-1-carboxylate facial triad sites is in MLCT
      transitions observed for both types of triads and reflects their difference in
      charge. These studies provide insight into the effects of perturbation of the
      facial triad ligation of the non-heme ferrous enzymes on their geometric and
      electronic structure and their possible contributions to reactivity.

PMID- 20695532
TI  - Redox-dependent domain rearrangement of protein disulfide isomerase from a
      thermophilic fungus.
AB  - Protein disulfide isomerase (PDI) acts as folding catalyst and molecular
      chaperone for disulfide-containing proteins through the formation, breakage, and
      rearrangement of disulfide bonds. PDI has a modular structure comprising four
      thioredoxin domains, a, b, b', and a', followed by a short segment, c. The a and
      a' domains have an active site cysteine pair for the thiol-disulfide exchange
      reaction, which alters PDI between the reduced and oxidized forms, and the b'
      domain provides a primary binding site for substrate proteins. Although the
      structures and functions of PDI have studied, it is still argued whether the
      overall conformation of PDI depends on the redox state of the active site
      cysteine pair. Here, we report redox-dependent conformational and solvation
      changes of PDI from a thermophilic fungus elucidated by small-angle X-ray
      scattering (SAXS) analysis. The redox state and secondary structures of PDI were
      also characterized by nuclear magnetic resonance and circular dichroic
      spectroscopy, respectively. The oxidized form of PDI showed SAXS differences from
      the reduced form, and the low-resolution molecular models restored from the SAXS
      profiles differed between the two forms regarding the positions of the a'-c
      region relative to the a-b-b' region. The normal mode analysis of the crystal
      structure of yeast PDI revealed that the inherent motions of the a-b-b' and a'-c
      regions expose the substrate binding surface of the b' domain. The apparent
      molecular weight of the oxidized form estimated from SAXS was 1.1 times larger
      than that of the reduced form, whereas the radius of gyration (ca. 33 A) was
      nearly independent of the redox state. These results suggest that the
      conformation of PDI is controlled by the redox state of the active site cysteine
      residues in the a and a' domains and that the conformational alternation
      accompanies solvation changes in the active site cleft formed by the a, b, b',
      and a' domains. On the basis of the results presented here, we propose a
      mechanism explaining the observed redox-dependent conformational and solvation
      changes of PDI.

PMID- 20695535
TI  - Adsorption-induced deformation of mesoporous solids.
AB  - The Derjaguin-Broekhoff-de Boer theory of capillary condensation is employed to
      describe deformation of mesoporous solids in the course of adsorption-desorption
      hysteretic cycles. We suggest a thermodynamic model, which relates the mechanical
      stress induced by the adsorbed phase to the adsorption isotherm. Analytical
      expressions are derived for the dependence of the solvation pressure on the vapor
      pressure. The proposed method provides a description of nonmonotonic hysteretic
      deformation during capillary condensation without invoking any adjustable
      parameters. The method is showcased drawing on the examples of literature
      experimental data on adsorption deformation of porous glass and SBA-15 silica.

PMID- 20695533
TI  - Identification of S-nitrosylated targets of thioredoxin using a quantitative
      proteomic approach.
AB  - Reversible protein cysteine nitrosylation (S-nitrosylation) is a common mechanism
      utilized in signal transduction and other diverse cellular processes. Protein
      denitrosylation is largely mediated by cysteine denitrosylases, but the
      functional scope and significance of these enzymes are incompletely defined, in
      part due to limited information on their cognate substrates. Here, using Jurkat
      cells, we employed stable isotope labeling by amino acids in cell culture
      (SILAC), coupled to the biotin switch technique and mass spectrometry, to
      identify 46 new substrates of one denitrosylase, thioredoxin 1. These substrates
      are involved in a wide range of cellular functions including cytoskeletal
      organization, cellular metabolism, signal transduction, and redox homeostasis. We
      also identified multiple S-nitrosylated proteins that are not substrates of
      thioredoxin 1. A verification of our principal findings was made in a second cell
      type (RAW264.7 cells). Our results point to thioredoxin 1 as a major protein
      denitrosylase in mammalian cells and demonstrate the utility of quantitative
      proteomics for large-scale identification of denitrosylase substrates.

PMID- 20695536
TI  - Simple synthesis of a library of zwitterionic surfactants via Michael-type
      addition of methacrylate and alkane thiol compounds.
AB  - A library of zwitterionic phosphorylcholine surfactants with various alkyl chain
      lengths and compositions was readily prepared from a combination of 2
      (methacryloyloxy)ethyl phosphorylcholine (MPC) and various alkanethiol compounds
      via Michael-type addition. The critical micelle concentration (CMC) was evaluated
      by surface tensiometry. At the CMC, the surface tension of these aqueous
      solutions decreased significantly to below 40 mN/m. For the zwitterionic
      surfactants composed of MPC, and fluoroalkane and alkanedithiol, the surface
      tension was approximately 24, and 50 mN/m, respectively. From the equation log
      (CMC) = A - Bn, where n is the number of carbon atoms in the alkyl chain, A and B
      were calculated as 1.09 and 0.44, respectively. The value of the slope B was
      between that of ionic (B = 0.30) and nonionic surfactants (B = 0.50). Despite the
      ionic nature of the surfactants, their behavior was closer to that of nonionic
      surfactants.

PMID- 20695537
TI  - Micromechanics model of liquid crystal anisotropic triple lines with applications
      to self-assembly.
AB  - Directed self-assembly of mesophases at three phase contact lines has been
      reported for a variety of solutions, including micelles, tobacco mosaic virus,
      DNA, silk, and others, through the action of capillary forces, wetting processes,
      and/or evaporation. This communication presents a new micromechanical line-excess
      model of the anisotropic contact line tension for nematic liquid crystal phases,
      which incorporates well characterized liquid crystal interfacial tensions. The
      anisotropic line tension is then used to formulate the contact line torque that
      promotes the azimuthal orientation, widely reported experimentally. The
      dependence of the line torque strength on the contact angle reveals the
      conditions that promote azimuthal orientational ordering close to the contact
      line. This work is limited to anisotropic line-excess tension, and wetting and
      evaporation processes are outside its scope.

PMID- 20695538
TI  - Nanosized emulsions stabilized by semisolid polymer interphase.
AB  - We introduce a new approach for stabilizing oil-in-water nanoemulsions using a
      semisolid interphase formed by the phase separation of amphiphilic block
      copolymers from the organic phase. This system is illustrated using an
      amphiphilic diblock copolymer, poly(ethylene oxide)-block-poly(epsilon
      caprolactone) (PEO-b-PCL), with commonly used oils. PEO-b-PCL can be miscible
      with oil at elevated temperatures (70-80 degrees C); however, polymer/oil
      demixing occurs as the temperature drops below the melting temperature of PEO-b
      PCL (approximately 55 degrees C). A homogeneous polymer/oil mixture was dispersed
      in water at 80 degrees C to generate embryonic emulsions, and then the emulsion
      size was reduced to a nanometer range through microfluidic homogenization. The
      structure of the generated nanoemulsions is irreversibly frozen as they are
      cooled down to ambient temperature. The nanoemulsions stabilized by PEO-b-PCL
      show the excellent colloidal stability against thermal and chemical stresses,
      exhibiting no significant changes in the size distribution during incubation for
      4 months at ambient temperature or 10 days at 60 degrees C. This study
      demonstrates that PEO-b-PCL is an attractive emulsifying material for practical
      nanoemulsion formulations requiring structural stability under a broad range of
      conditions.

PMID- 20695539
TI  - Two-particle interfacial microrheology at polymer-polymer interfaces.
AB  - We continue to develop two-particle interfacial microrheology and have applied
      the technique to study the interfacial viscoelastic properties of immiscible
      poly(dimethylsiloxane) (PDMS)-poly(ethylene glycol) (PEG) interfaces. The
      interfacial storage and loss moduli are measured over a wide frequency range: at
      low frequencies, the interfaces are dominated by viscous responses whereas
      elasticity dominates at high frequencies. The zero-shear interfacial viscosity,
      estimated following the Cox-Merz rule and Cross model, falls between the bulk
      viscosities of the two individual polymers. Surprisingly, the interfacial
      relaxation time, calculated from the crossover of the storage and loss moduli, is
      observed to be an order of magnitude larger than that of the PDMS bulk polymers.
      The effects of tracer particle surface chemistry and size have also been
      investigated and show minimum influences on two-particle interfacial
      microrheology.

PMID- 20695540
TI  - Construction of microbelts through the coassembly of a disclike molecule and
      primary alkyl ammoniums: a noncovalent strategy to mimic covalently bonded pi
      core alkyl chain structure.
AB  - In this letter, we report the fabrication of microbelts through the coassembly of
      hexa-2-pyridyl-hexaazatriphenylen (HPHAT), a disklike pi-conjugated molecule,
      with primary alkyl ammonium triflate. The strategy is first to construct hydrogen
      bonded complexes between HPHAT and primary alkyl ammoniums to mimic covalently
      bonded pi-core alkyl chain structures, and then the complexes self-assemble into
      microbelts driven by pi-pi stacking in the pi core and van der Waals interactions
      between the peripheral alkyl chains. The morphology of as-prepared microbelts has
      been characterized with scanning electron microscopy (SEM), optical microscopy,
      polarizing microscopy, and transmission electron microscopy (TEM). Spectroscopic
      and crystallographic investigations were also carried out to reveal the formation
      mechanism of the microbelts, through which a sequential self-assembly process has
      been proposed.

PMID- 20695541
TI  - Rapid fabrication of bimetallic spherical motors.
AB  - Catalytic bimetallic nanomotors can swim at 100 body lengths per second as well
      as pick up, haul, and release micrometer-scale cargo. The electrokinetic
      locomotion of bimetallic nanomotors is driven by the electrocatalytic
      decomposition of hydrogen peroxide. The motors are typically fabricated by
      electrodeposition-based template synthesis techniques that result in
      heterogeneous samples and require specialized knowledge of electrochemistry, a
      three-electrode potentiostat setup, cyanide-based chemistry, and porous
      membranes. This paper presents a rapid and facile method for fabrication of
      spherical bimetallic motors that only requires access to metal deposition
      equipment and commercially available microspheres. The resulting spherical motors
      swim at speeds comparable to rod-shaped motors with the same dimensions and
      composition. The spherical motors' velocity increases with fuel concentration and
      decreasing diameter.

PMID- 20695542
TI  - Synthesis, properties, and electronic applications of size-controlled poly(3
      hexylthiophene) nanoparticles.
AB  - Semiconducting polymer nanoparticles have attracted increasing interest for the
      facile fabrication of organic electronic devices. These nanoparticles could
      provide the ability to control thin film morphology independently of optical and
      electronic properties. Using poly(3-hexylthiophene), we demonstrate surfactant
      free synthesis and characterization of size-controlled, semicrystalline polymer
      nanoparticles. Our method produces discrete nanoparticles that can be deposited
      from solution into thin films. By controlling the molecular weight,
      polydispersity, and regioregularity of the polymer as well as varying its initial
      solution concentration, we tune both the size and crystallinity of the resulting
      nanoparticles. Organic field effect transistors (OFETs) using nanoparticles made
      from this method produce good semiconducting devices with hole mobilities on the
      order of 10(-3) cm(2)/(V s). This approach to forming polymer nanoparticles is
      attractive for the introduction of solution-processable, well-characterized
      nanoscale crystalline domains of a variety of conjugated polymers and should be
      useful for the fabrication and optimization of organic electronic devices.

PMID- 20695543
TI  - Carbon nanotubes noncovalently functionalized by an organic-inorganic hybrid: new
      building blocks for constructing superhydrophobic conductive coatings.
AB  - A facile method for constructing superhydrophobic, conductive, and
      transparent/translucent coatings is presented. Pristine multiwalled carbon
      nanotubes (MWNTs) are first noncovalently (wrapped) modified by an organic
      inorganic hybrid of an amphiphilic copolymer of styrene and maleic anhydride and
      silica with the existence of gamma-aminopropyltriethoxysilane (a silane coupling
      agent). The modified MWNTs were mixed with tetraethyl orthosilicate in ethanol,
      air sprayed, coated with a fluoroalkylsilane, and then heat treated to obtain the
      superhydrophobic, conductive, and transparent/translucent coatings. Scanning
      electron microscopy shows that the coatings have a micrometer- and nanometer
      scale hierarchical structure similar to that of lotus leaves; therefore, they
      show both high water contact angles (>160 degrees) and low sliding angles (<2
      degrees). The coatings also exhibit good transmittance and greatly improved
      conductivities. This method is convenient, inexpensive, and easy to scale up.
      Moreover, it does not require any chemical modification of the MWNTs or use any
      harsh chemicals.

PMID- 20695544
TI  - Influence of surface functionalization on the growth of gold nanostructures on
      graphene thin films.
AB  - We developed a surface-chemistry-based approach to investigating the influence of
      surface functionalization on the growth of gold nanostructures on graphene thin
      films by utilizing various pyrene derivatives presenting different functional
      groups. Among the surface-modifying molecules, decylpyrene (DP) yielded the
      highest content of gold rods (average 22 +/- 4%) among gold nanostructures on
      graphene films when a graphene surface was pretreated with DP prior to gold
      nanostructure growth. The improved yield of gold rods on graphene thin films
      enhanced several physical properties of graphene such as the electrical
      conductivity and Raman signals by 6.3- and 14.7-fold, respectively.

PMID- 20695545
TI  - Effective size and zeta potential of nanorods by Ferguson analysis.
AB  - The effective hydrodynamic size and free mobility of particles of varying aspect
      ratio were evaluated by Ferguson analysis of gel electrophoresis. The ligand
      layer thickness was estimated from the difference between the effective size and
      the size of the metal core from TEM imaging. The zeta potential of the particles
      was calculated from the Ferguson analysis result by applying conventional
      electrophoresis theories for spheres and cylinders. The results show that Henry's
      solution for spherical particles can be used to obtain the zeta potential of
      cylindrical particles without requiring the use of TEM for size analysis.

PMID- 20695546
TI  - Comparing molecular gelators and nongelators based on solubilities and solid
      state interactions.
AB  - The relationship between molecular structure and gelation ability was
      investigated for a series of pyridine-based compounds. Nineteen compounds were
      synthesized and screened for gelation. Of these, eight were discovered to be
      gelators for a variety of organic solvent/water combinations. Solubility studies
      on the bulk powders revealed that gelators and nongelators are indistinguishable
      based on their room temperature solubilities. Likewise, X-ray diffraction
      experiments indicated that the presence (or absence) of 1D intermolecular
      interactions does not correlate with gelation ability. van't Hoff analyses of the
      temperature-dependent solubilities revealed that the majority of gelators have
      higher dissolution enthalpies and entropies than nongelators. In combination,
      these data suggest a complex relationship between molecular structure and
      gelation ability.

PMID- 20695547
TI  - Potential of mean force for K+ in thin water films on cleaved mica.
AB  - The atomically smooth surface of cleaved K(+)-mica is a common substrate for
      investigations of various phenomena at the mineral-water interface. In this
      study, K(+) inner-sphere adsorption above tetrahedral substitutions in the mica
      structure is found to be more favorable than that in mica's ditrigonal cavities
      for both dehydrated and hydrated cleaved mica. The activation energy necessary to
      transfer K(+) from the inner-sphere adsorption state to the outer-sphere
      adsorption state, in which K(+) can presumably migrate parallel to the surface,
      is calculated to be 45-48 kJ/mol on hydrated cleaved mica. The K(+) desorption
      state is predicted to be >13 A above the mica surface.

PMID- 20695548
TI  - Fracture of protein fibrils as induced by elongational flow.
AB  - The length distribution of whey protein fibrils is important for application
      purposes. However, it is hard to influence the length distribution of whey
      protein fibrils during production. One way of influencing the length distribution
      of the mature fibrils is exposing them to an external field, like a flow field.
      In this research whey protein fibrils were exposed to elongational flow to
      fracture the fibrils. A simple experimental setup was used to establish a range
      of elongational strain rates. The length distribution of the fractured fibrils
      was determined using transmission electron microscopy and was shown to be
      controllable at relatively low strain rates.

PMID- 20695549
TI  - Interactions between DNA and nonionic ethylene oxide surfactants are
      predominantly repulsive.
AB  - In the present work, the interactions between double-stranded (ds) or single
      stranded (ss) DNA and nonionic ethylene oxide (EO) surfactants, with special
      attention to the possible contributions from hydrophobic interactions, have been
      investigated using a multitechnique approach. It was found that the presence of
      ss as well as dsDNA induces a slight decrease of the cloud point of pentaethylene
      glycol monododecyl ether (C(12)E(5)). Assessment of the partitioning of DNA
      between the surfactant-rich and surfactant-poor phases formed above the cloud
      point showed that the polymer was preferably located in the surfactant-poor
      phase. Surface tensiometry experiments revealed that neither of the DNA forms
      induced surfactant micellization. Finally, it was shown by DNA melting
      measurements that another EO surfactant (C(12)E(8)) did not affect the relative
      stabilities of ss and dsDNA. To summarize, all experiments suggest that the net
      interaction between DNA and nonionic surfactants of the EO type is weakly
      repulsive, which can be attributed mainly to steric effects. In general, the
      results were practically identical for the ds and ss forms of DNA, except those
      from the cloud point experiments, where the decrease of the cloud point was less
      pronounced with ssDNA. This finding indicates the presence of an attractive
      component in the interaction, which can reasonably be ascribed to hydrophobic
      effects.

PMID- 20695551
TI  - Pickering emulsion as a template to synthesize Janus colloids with anisotropy in
      the surface potential.
AB  - A versatile new concept is presented for the synthesis of Janus colloids composed
      of Laponite nanoclay armored poly(divinylbenzene) with an anisotropic surface
      potential via a double Pickering emulsion template. First, polystyrene or
      poly(divinylbenzene) colloids stabilized with Laponite nanoclay are synthesized
      via a Pickering miniemulsion approach. These nanoparticle-stabilized colloids
      were then templated at a wax-water interface in a second Pickering emulsion in
      order to chemically modify one hemisphere of the colloids. Janus modification of
      the colloids was accomplished by cation exchange of sodium ions, originally
      present on the surface of the Laponite with various salts of modifying ions
      (Ca(2+), Fe(2+), and Fe(3+)) in the suspension. The zeta potential of the
      chemically modified and unmodified colloids was compared. The maximum change in
      the zeta potential was given by the calcium ions, Ca(2+)-adsorbed modified
      colloids as compared to unmodified sodium ions, Na(+)-adsorbed colloids. The
      distribution of charges on the Janus colloids results in a nonuniform zeta
      potential. XPS and optical microscopy were used to verify the successful chemical
      modification by the cation exchange of Na(+) for Ca(2+) ions on one hemisphere of
      the Janus colloids.

PMID- 20695550
TI  - Solution X-ray scattering form factors of supramolecular self-assembled
      structures.
AB  - In this paper, the analysis of several involved models, relevant for evaluating
      solution X-ray scattering form factors of supramolecular self-assembled
      structures, is presented. Different geometrical models are discussed, and the
      scattering form factors of several layers of those shapes are evaluated. The
      thickness and the electron density of each layer are parameters in those models.
      The models include Gaussian electron density profiles and/or uniform electron
      density profiles at each layer. Various forms of cuboid, layered, spherical,
      cylindrical, and helical structures are carefully treated. The orientation
      averaged scattering intensities of those form factors are calculated. Similar
      classes of form factors are examined and compared, and their fit to scattering
      data of lipid bilayers, capsids of the Simian virus 40 virus-like particle and
      microtubule is discussed. A more detailed model of discrete helices composed of
      uniform spheres was derived and compared to solution X-ray scattering data of
      microtubules. Our analyses show that when high-resolution data are available the
      more detailed models with Gaussian electron density profiles or helical
      structures composed of spheres should be used to better capture all the elements
      in the scattering curves. The models presented in this paper may also be applied,
      with minor corrections, for the analysis of solution neutron scattering data.

PMID- 20695552
TI  - Structure and kinetics of shear aggregation in turbulent flows. I. Early stage of
      aggregation.
AB  - Aggregation of rigid colloidal particles leads to fractal-like structures that
      are characterized by a fractal dimension d(f) which is a key parameter for
      describing aggregation processes. This is particularly true in shear aggregation
      where d(f) strongly influences aggregation kinetics. Direct measurement of d(f)
      in the early stages of shear aggregation is however difficult, as the aggregates
      are small and few in number. An alternative method for determining d(f) is to use
      an aggregation model that when fitted to the time evolution of the cluster mass
      distribution allows for estimating d(f). Here, we explore three such models, two
      of which are based on an effective collision sphere and one which directly
      incorporates the permeable structure of the aggregates, and we apply them for
      interpreting the initial aggregate growth measured experimentally in a turbulent
      stirred tank reactor. For the latter, three polystyrene latexes were used that
      differed only in the size of the primary particles (d(p) = 420, 600, and 810 nm).
      It was found that all three models describe initial aggregation kinetics
      reasonably well using, however, substantially different values for d(f). To
      discriminate among the models, we therefore also studied the regrowth of
      preformed aggregates where d(f) was experimentally accessible. It was found that
      only the model that directly incorporates the permeable structure of the
      aggregates is able to predict correctly this second type of experiments. Applying
      this model to the initial aggregation kinetics, we conclude that the actual
      initial fractal dimension is d(f) = 2.07 +/- 0.04 as found from this model.

PMID- 20695553
TI  - Effect of micellar and reverse micellar interface on solute location: 2,6
      pyridinedicarboxylate in CTAB micelles and CTAB and AOT reverse micelles.
AB  - The interface-solute interactions, including solute location, surfactant charge,
      and geometry of solute interactions were studied in CTAB micelles and reverse
      micelles and were found to be similar as measured using (1)H NMR spectroscopy and
      a pH-sensitive probe. (1)H NMR spectra were recorded in the presence and absence
      of 2,6-pyridinedicarboxylate probe at CTAB concentrations above and below the
      critical micelle concentration showing interaction between dipic-probe and the
      micellar self-assembled structure. Downfield chemical shifts are observed for the
      CTAB surfactant signals upon aggregation and micelle formation. The effect of
      micelle formation on CTAB chemical shifts was quantitated, and simple ion pairing
      was ruled out. No significant change in CTAB surfactant signals are observed in
      the presence of monoanionic probe, whereas significant shifts are observed in the
      presence of the dianionic probe. The (1)H NMR spectra of the dipic-probe are
      diagnostic of the protonation state and isomeric form of the dipic-probe. The
      (1)H NMR chemical shifts in micelles are sensitive to the location of the dipic
      probe, and the downfield chemical shift suggests location of part of the molecule
      in the Stern layer near the charged interface. Other parts of the probe show an
      upfield chemical shifts consistent with a deeper penetration of the dipic-probe
      into the surfactant layer. Probe location was confirmed using the 2D ROESY.
      Spectra recorded of the dipic-probe at various pH values demonstrate that both
      CTAB micellar and CTAB/pentanol/cyclohexane reverse micellar interfaces are
      different than those reported in aqueous solution and in AOT/isooctane reverse
      micelles (Crans et al. J. Org. Chem. 2008, 73, 9633-9640) and suggest interface
      penetration by dipic(2-). Together these observations and comparisons provide
      guidelines for future interpretation of chemical shift changes in both micelles
      and reverse micelles and point to headgroup charge as being a key factor
      determining the direction of chemical shift change and the depth of solute
      penetration.

PMID- 20695554
TI  - Self-stratification during film formation from latex blends driven by differences
      in collective diffusivity.
AB  - Coatings with vertical gradients in composition were produced by drying an
      aqueous polymer dispersion containing both charged and neutral particles. After
      drying, the neutral component was enriched at the film/air interface. The
      spontaneous vertical segregation between the two types of particles goes back to
      a difference in collective diffusivity. As the film dries, a layer enriched in
      polymer develops at the top. Due to their mutual repulsion, charged spheres
      escape from this layer more quickly than their neutral counterparts. Provided
      that the total time of drying is between the times of diffusion for the two types
      of particles (approximately H(0)(2)/D(c) with H(0) the initial film thickness and
      D(c) the collective diffusivity of the respective species), a concentration
      gradient persists after the film has turned dry. This effect can be used to
      create a functionally graded material (FGM) in a single coating step.

PMID- 20695555
TI  - Functionalization of diamond nanoparticles using "click" chemistry.
AB  - The paper reports on covalent linking of different alkyne-containing (decyne,
      ethynylferrocene, and N-propargyl-1-pyrenecarboxamide) compounds to azide
      terminated nanodiamond (ND) particles. Azide-terminated particles (ND-N(3)) were
      obtained from amine-terminated nanodiamond particles (ND-NH(2)) through the
      reaction with 4-azidobenzoic acid in the presence of a carbodiimide coupling
      agent. Functionalized ND particles with long alkyl chain groups can be easily
      dispersed in various organic solvents without any apparent precipitation after
      several hours. The course of the reaction was followed using Fourier transform
      infrared (FT-IR) spectroscopy, UV/vis spectroscopy, fluorescence, cyclic
      voltammetry, thermogravimetric analysis (TGA), and particle size measurements.
      The surface loading of pyrene bearing a terminal acetylene group was found to be
      0.54 mmol/g. Because of its gentle nature and specificity, the chemistry
      developed in this work can be used as a general platform for the preparation of
      functional nanoparticles for various applications.

PMID- 20695556
TI  - Large-scale colloidal self-assembly by doctor blade coating.
AB  - This article reports a simple, roll-to-roll compatible coating technology for
      producing 3D highly ordered colloidal crystal-polymer nanocomposites, colloidal
      crystals, and macroporous polymer membranes. A vertically beveled doctor blade is
      utilized to shear align silica microsphere-monomer suspensions to form large-area
      nanocomposites in a single step. The polymer matrix and the silica microspheres
      can be selectively removed to create colloidal crystals and self-standing
      macroporous polymer membranes. The thickness of the shear-aligned crystal is
      correlated with the viscosity of the colloidal suspension, and the coating speed
      and the correlations can be qualitatively explained by adapting the mechanisms
      developed for conventional doctor blade coating. We further demonstrate that the
      doctor blade coating speed can be significantly increased by using a dual-blade
      setup. The optical properties of the self-assembled structures are evaluated by
      normal-incidence reflection measurements, and the experimental results agree well
      with the theoretical predictions using Bragg's law and a scalar wave
      approximation model. We have also demonstrated that the templated macroporous
      polymers with interconnected voids and uniform interconnecting nanopores can be
      directly used as filtration membranes to achieve size-exclusive separation of
      particles.

PMID- 20695557
TI  - Ligand conjugation to bimodal poly(ethylene glycol) brush layers on microbubbles.
AB  - Using microbubbles as model systems, we examined molecular diffusion and binding
      to colloidal surfaces in bimodal poly(ethylene glycol) (PEG) brush layers. A
      microbubble is a gaseous colloidal particle with a diameter of less than 10 mum,
      of which the surface comprises amphiphilic phospholipids self-assembled to form a
      lipid monolayer shell. Due to the compressible gas core, microbubbles provide a
      sensitive acoustic response and are currently used as ultrasound contrast agents.
      Similar to the design of long circulating liposomes, PEG chains are typically
      incorporated into the shell of microbubbles to form a steric barrier against
      coalescence and adsorption of macromolecules to the microbubble surface. We
      introduced a buried-ligand architecture (BLA) design where the microbubble
      surface was coated with a bimodal PEG brush. After microbubbles were generated,
      fluorescent ligands with different molecular weights were conjugated to the
      tethered functional groups on the shorter PEG chains, while the longer PEG chains
      served as a shield to protect these ligands from exposure to the surrounding
      environment. BLA microbubbles reduced the binding of macromolecules (>10 kDa) to
      the tethers due to the steric hindrance of the PEG overbrush while allowing the
      uninhibited attachment of small molecules (<1 kDa). Roughly 40% less fluorescein
      conjugated streptavidin (SA-FITC) bound to BLA microbubbles compared to exposed
      ligand architecture (ELA) microbubbles. The binding of SA-FITC to BLA
      microbubbles suggested a possible phase separation between the lipid species on
      the surface leading to populations of revealed and concealed ligands. Ligand
      conjugation kinetics was independent of microbubble size, regardless of ligand
      size or microbubble architecture. We observed, for the first time, streptavidin
      induced surface structure formation for ELA microbubbles and proposed that this
      phenomenon may be correlated to flow cytometry scattering measurements. We
      therefore demonstrated the feasibility of postlabeling for small-molecule ligands
      to BLA microbubbles to generate stealth targeted ultrasound contrast agents.

PMID- 20695559
TI  - Thermotropic liquid crystals of a non-mesogenic group bearing surfactant
      encapsulated polyoxometalate complexes.
AB  - A tri(ethylene oxide)octadecyldimethylammonium p-toluenesulfonate (C(18)NEO(3) x
      Ts) amphiphile was employed to encapsulate Keggin-type polyoxometalates by ion
      metathesis reactions with phosphotungstic acid, silicotungstic acid,
      pentapotassium dodecatungstoborate(III), and phosphomolybdic acid, giving the
      surfactant-encapsulated polyoxometalates (SEPs) in SEP-P, SEP-Si, SEP-B, and SEP
      PMo, respectively. Meanwhile, a C(18)NEO(3) x PF(6) amphiphile was prepared by
      substituting the p-toluenesulfonate of C(18)NEO(3) x Ts with hexafluorophosphate.
      The chemical composition of all SEPs and amphiphiles was characterized through
      (1)H NMR, infrared spectroscopy, mass spectroscopy, elemental analysis, and
      thermogravimetric analysis. The thermal properties of the SEPs and the
      amphiphiles were investigated by differential scanning calorimetry, polarized
      optical microscopy, and variable-temperature X-ray diffraction. The types of
      anions have a remarkable influence on the thermal properties of the prepared
      compounds or complexes. C(18)NEO(3) x Ts displays a smectic A phase with low
      transition temperatures, and C(18)NEO(3) x PF(6) is a near-room-temperature ionic
      liquid. In contrast to the fact that SEP-Si and SEP-PMo decompose upon just
      reaching or before reaching the isotropic liquid state, both SEP-P and SEP-B
      reveal smectic B phase structures. The present results indicate that the
      combination of proper cationic amphiphiles and polyoxometalates can impart
      typical thermotropic liquid-crystalline behavior to SEPs, although no mesogenic
      groups are introduced into the complex systems.

PMID- 20695560
TI  - Impact of polymer graft characteristics and evaporation rate on the formation of
      2-D nanoparticle assemblies.
AB  - The effect of polymer functionalization on the two-dimensional (2-D) assembly of
      uniform as well as highly asymmetric binary colloidal mixtures with both neutral
      and incompatible polymer grafts is presented. In ordered assemblies of uniform
      particle brush systems, the observed size-segregation is analogous to that of
      hard sphere colloidal systems, suggesting that lateral capillary interactions are
      responsible for the crystal nucleation in the early stages of assembly formation.
      Structure formation in binary blends of asymmetric particle brush systems is
      found to be strongly influenced by three major energetic contributions, that is,
      the interfacial energies associated with the particle brush/air boundaries, the
      interfacial energies between the distinct brush components, as well as the
      elastic energy associated with the stretching of the polymer-brush to fill the
      interstitial regions within locally ordered particle arrays. Our results
      demonstrate the relevance of capillary interactions in soft particle brush
      systems but also highlight distinctive differences in the order formation as
      compared to hard sphere colloidal systems. In particular, the compliant response
      of grafted polymer chains is shown to promote phase separation in binary blends
      of incompatible and asymmetric colloidal systems.

PMID- 20695561
TI  - Structural evolution of a colloidal crystal fiber during heating and annealing
      studied by in situ synchrotron small angle X-ray scattering.
AB  - The structural evolution of a colloidal crystal fiber during heating and
      annealing was followed by in situ synchrotron small-angle X-ray scattering. The
      polymer dispersion (with a particle size of 118 nm) from which the fibers were
      formed by directed drying contained emulsifier and salt. A cellular structure
      formed upon drying in which the percolating phase (the "membrane phase") is
      composed from these components; this membrane phase gives rise to the scattering
      contrast on which the present observations build. Changes of the lattice constant
      of the colloidal crystallites and the intensity evolution of the scattering from
      the crystalline and the amorphous phases during heating and annealing indicate
      characteristic temperatures where the system exhibits pronounced structural
      changes. The first characteristic temperature was identified as 125 degrees C
      above which residue water in the membrane material was evaporated leading to
      shrinkage of the colloidal crystalline lattice. At a temperature above about 140
      degrees C the membrane material was expelled out of the crystalline domains. This
      effect is accompanied by the progressive interdiffusion of polymer chains between
      adjacent latex particles and leads to further thermal shrinkage of the colloidal
      crystals. The second characteristic temperature is defined by a rapid increase in
      isotropic scattering. This effect is attributed to the formation of increasingly
      large domains of the membrane material and the concomitant disappearance of the
      membrane phase from the former crystal domains.

PMID- 20695562
TI  - Molecularly ordered decanethiolate self-assembled monolayers on Au(111) from in
      situ cleaved decanethioacetate: an NMR and STM study of the efficacy of reagents
      for thioacetate cleavage.
AB  - The cleavage of decanethioacetate (C10SAc) has been studied by (1)H nuclear
      magnetic resonance (NMR) spectroscopy and scanning tunneling microscopy (STM)
      imaging of in situ prepared decanethiolate self-assembled monolayers (SAMs) on
      Au(111). Solutions of C10SAc (46 mM) and previously reported cleavage reagents
      (typically 58 mM) in CD(3)OD were monitored at 20 degrees C by NMR spectroscopy.
      Cleavage by ammonium hydroxide, propylamine, or hydrochloric acid was not
      complete within 48 h; cleavage by potassium carbonate was complete within 24 h
      and that by potassium hydroxide or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU)
      within 2 h. Similar cleavage rates were observed for phenylthioacetate. The
      degree of molecular ordering determined by STM imaging increased with increasing
      extent of in situ cleavage by these same reagents (2.5 mM C10SAc and 2.5 mM
      reagent in ethanol for 1 h, then 16 h immersion of Au/mica). Less effective
      cleavage reagents did not cleave the C10SAc sufficiently to decanethiol (C10SH)
      and gave mostly disordered SAMs. In contrast, KOH or DBU completely cleaved the
      C10SAc to C10SH and led to well-ordered SAMs composed of (square root(3) x square
      root(3))R30 degrees domains that are indistinguishable from SAMs grown from
      C10SH. Monolayer formation from thioacetates in the absence of cleavage agents is
      likely due to thiol or disulfide impurity in the thioacetates. Eliminating
      disulfide by using Bu(3)P as a sacrificial reductant also helped to produce good
      molecular order in the SAM. The methods presented here allow routine growth of
      molecularly ordered alkanethiolate SAMs from thioacetates using reagents of
      ordinary purity under ambient, benchtop conditions.

PMID- 20695558
TI  - Polymeric crowding agents improve passive biomacromolecule encapsulation in lipid
      vesicles.
AB  - Large solutes such as high molecular weight proteins can be difficult to
      encapsulate in lipid vesicles. Passive trapping of these macromolecular solutes
      during vesicle formation typically results in concentrations inside the vesicles
      that are much lower than in the external solution. Here, we investigated the
      effect of macromolecular crowding on passive encapsulation of biological
      macromolecules with molecular weights ranging from 52 kDa to 660 kDa within both
      individual giant lipid vesicles (GVs, > 3 microm diameter) and populations of 200
      nm diameter large unilamellar vesicles (LUVs). Fluorescently labeled
      biomacromolecules were encapsulated during vesicle formation in the presence or
      absence of three weight percent poly(ethylene glycol) (PEG; 8 kDa) or dextran 500
      kDa, which served as crowding agents. Encapsulation efficiency of the labeled
      biomolecules was higher for the lower molecular weight solutes, with internal
      concentrations essentially equal to external concentrations for labeled
      biomacromolecules with hydrodynamic radii (r(h)) less than 10 nm. In contrast,
      internal concentrations were reduced markedly for larger solutes with r(h) > or =
      10 nm. Addition of PEG or dextran during vesicle formation improved encapsulation
      of these larger proteins up to the same levels as observed for the smaller
      proteins, such that internal and external concentrations were equal. This
      observation is consistent with PEG and dextran acting as volume excluders,
      reducing the hydrodynamic radius of the biomacromolecules and increasing their
      encapsulation. This work demonstrates a simple and general route to improved
      encapsulation of otherwise poorly encapsulated macromolecular solutes in both GV
      and LUVs up to their concentration in the solution present during vesicle
      formation.

PMID- 20695563
TI  - Effect of surface structure of kaolinite on aggregation, settling rate, and bed
      density.
AB  - The flocculation and solid/liquid separation of four well-characterized
      kaolinites (2 well, 2 poorly crystallized) have been studied for comparison of
      surface structure (SEM), aggregate structure during flocculation (cryo-SEM),
      settling rate, and bed density (with raking). It is shown that major differences
      in these properties are largely due to crystallinity and consequent surface
      structure of the extensive (larger dimension "basal") face. Well-crystallized
      kaolinites, with higher Hinckley indices and lower aspect ratios, have relatively
      smooth, flat basal surfaces and thicker edge planes promoting both effective
      initial bridging flocculation (largely edge-edge) and structural rearrangement to
      face-face during the raking process. This results in faster settling rates and
      more compact bed structures. Poorly crystallized kaolinites, with low Hinckley
      indices and high aspect ratios, exhibit ragged, stepped structures of the
      extensive face with a high proportion of nanosized islands forming cascade-like
      steps (i.e., multiple edges) contributing up to 30% of the specific surface area
      and providing flocculant adsorption sites (hydroxyl groups) across this extensive
      face. This leads to bridging flocculation taking place on both edge and extensive
      ("basal") planes, producing low-density edge-face structures during flocculation
      which leads to slow settling rates and poor bed densities. In particular, the
      complex surface morphology of the poorly crystallized kaolinites resists the
      transformation of edge-face structures to dense face-face structures under shear
      force introduced by raking. This results in low sediment density for poorly
      crystallized kaolinites. The studies suggest that the main influence on settling
      rates and bed densities of kaolinites in mineral tailings is likely to be related
      to the crystallinity and surface morphology of the kaolinite. They also suggest
      that interpretation of kaolinite behavior based on models of a flat (001) basal
      plane and edge sites only at the particle boundaries is not likely to be adequate
      for many real, less-crystallized kaolinites.

PMID- 20695564
TI  - Monitoring N719 dye configurations on (1 x n)-reconstructed anatase (100) by
      means of STM: reversible configurational changes upon illumination.
AB  - We report experimental results concerning the STM imaging of cis-bis
      (isothiocyanate)-bis-(2,2'-bipyridyl
      4,4'dicarboxylate)ruthenium(II)bis(tetrabutylammonium) dye (known as N719)
      adsorbed on a single crystal of anatase TiO(2)(100). The cleaning pretreatment,
      by sputtering and annealing, of TiO(2)(100) yields a reproducible (1 x n) surface
      reconstruction. Previous to dye deposition, TiO(2) was covered with one monolayer
      of 4-tert-butylpyridine (4-TBP) in ultrahigh vacuum (UHV) in order to protect the
      surface against air contamination. N719 was subsequently deposited by dipping the
      crystal into the dye solution. 4-TBP was removed partially in the solution and
      totally by heating the sample to around 285-300 degrees C in UHV. The images of
      the deposited 4-TBP on TiO(2)(100) revealed a complete surface coverage showing
      three modes of adsorption on TiO(2). The relatively uncomplicated desorption of 4
      TBP enables the accommodation and chemisorption of most N719 molecules directly
      onto the TiO(2) surface. The STM imaging of N719 was affected, in a reversible
      way, by illumination, because the quality of the image changed after a few hours
      in the dark or under illumination conditions. The results presented herein are
      discussed in terms of changes in molecular configurations and in open circuit
      potentials.

PMID- 20695565
TI  - Do epitaxy and temperature affect oscillatory solvation forces?
AB  - We present temperature-dependent atomic force microscope (AFM) measurements in
      force-distance mode of confined 1-dodecanol. Upon approach of the AFM-tip toward
      the highly oriented pyrolytic graphite (HOPG) surface, the final liquid film-
      only a few nanometers thin--is squeezed out in discrete layers. We find that both
      the force needed to squeeze out these layers and the number of structured layers
      strongly increase as the freezing temperature is approached. Surprisingly the
      force increases nonmonotonically and show a local maximum around 3 degrees and a
      local minimum at 1 degree above the bulk melting point of the liquid. We
      attribute this result to changes in epitaxial effects between 1-dodecanol and the
      HOPG surface close to the melting point of the liquid. To test this hypothesis we
      performed the same measurements in hexadecane, a similar carbon-chain molecule,
      and octamethylcyclotetrasiloxane (OMCTS), a quasi-spherical molecule. Hexadecane
      shows the same maximum in the squeeze-out force at 4-5 degrees and a minimum at 1
      2 degrees above the freezing temperature of the liquid, while the squeeze-out of
      OMCTS was found to be independent of temperature.

PMID- 20695566
TI  - Capillary filling in closed end nanochannels.
AB  - We investigated the interactions between liquid, gas, and solid phases in the
      capillary filling process of closed-end nanochannels. This paper presents
      theoretical models without and with absorption and diffusion of gas molecules in
      the liquid. Capillary filling experiments were carried out in closed-end silicon
      nanochannels with different lengths. The theoretical and measured characteristics
      of filling length versus time are compared. The results show that the filling
      process consists of two stages. The first stage resembles the capillary filling
      process in an open-end nanochannel. However, a remarkable discrepancy between the
      experimental results and the theory without gas absorption is observed in the
      second stage. A closer investigation of the second stage reveals that the
      dissolution of gas in the liquid is important and can be explained by the model
      with gas absorption and diffusion.

PMID- 20695567
TI  - Computation of contact lines on randomly heterogeneous surfaces.
AB  - Liquid wetting on real solid surfaces is significantly more complex than it is on
      the idealized surfaces of Young's equation. In the case of chemically
      heterogeneous solid surfaces, simulations of wetting have been carried out only
      for regularly patterned or one-dimensional surfaces. We describe a computational
      method for calculating advancing and receding contact lines on two-dimensional
      solid surfaces with arbitrary patterns of chemical heterogeneity. Results are
      verified against analytical solutions for homogeneous, single-defect, and striped
      surfaces. More practical surfaces with randomly placed high energy defects are
      also modeled. Realistic scatter in the contact angles as well as contact angle
      hysteresis and stick-slip motion are observed in the simulations. Hysteresis
      increases with the density of defects, but less so at high densities. The method
      allows prediction of wetting behavior from surface chemistry for a wide range of
      heterogeneous surfaces.

PMID- 20695568
TI  - Effect of chloride ions on the adsorption of 3-mercapto-1-propanesulfonic acid
      and bis(3-sulfopropyl)-disulfide on a Au(111) surface.
AB  - In situ scanning tunneling microscopy (STM) and cyclic voltammetry (CV) were used
      to study the adsorption of 3-mercapto-1-propanesulfonic acid (MPS) and bis(3
      sulfopropyl)-disulfide (SPS) on Au(111) electrode in a HClO(4) aqueous solution.
      Chloride ions were introduced into the electrolyte solution, and their effect on
      the adsorption behavior of MPS and SPS was investigated. The CV results show that
      SPS and MPS molecules preferentially adsorb on the Au(111) surface compared to
      chloride ions, and furthermore, chloride ion can induce the adsorption of thiol
      molecules on the Au(111) surface. In the absence of chloride, no adsorption phase
      of SPS (or MPS) adlayer can be imaged by STM at low potentials. Raising electrode
      potential leads to the appearance of disordered adsorption phase at ca. 0.4 V (vs
      RHE) and ordered adlattices at ca. 0.8 V. In the presence of chloride, ordered
      adsorption structures of SPS and MPS appear at a lower potential (0.2 V),
      implying the enhancement effect of chloride to the thiol adsorption. It is
      inferred that the presence of chloride ions triggers a more positively charged
      gold surface, enhancing the reaction rate of thiol adsorption. Furthermore, the
      presence of chloride also leads to a decrease in the thiol-electrolyte
      interaction, due to the high solvation effect of chloride ions, which promotes
      the adsorption of SPS and MPS onto the Au surface. With further elevation of
      electrode potential, electrostatic interaction leads to coadsorption of chloride
      ions into the adlayer, as well as orientation changes of the ad-molecules. As a
      result, the ordered adlattice was disrupted and disappeared at ca. 0.5 V.

PMID- 20695569
TI  - Micrometer-sized water droplet impingement dynamics and evaporation on a flat dry
      surface.
AB  - A comprehensive numerical and experimental investigation on micrometer-sized
      water droplet impact dynamics and evaporation on an unheated, flat, dry surface
      is conducted from the standpoint of spray-cooling technology. The axisymmetric
      time-dependent governing equations of continuity, momentum, energy, and species
      are solved. Surface tension, wall adhesion effect, gravitational body force,
      contact line dynamics, and evaporation are accounted for in the governing
      equations. The explicit volume of fluid (VOF) model with dynamic meshing and
      variable-time stepping in serial and parallel processors is used to capture the
      time-dependent liquid-gas interface motion throughout the computational domain.
      The numerical model includes temperature- and species-dependent thermodynamic and
      transport properties. The contact line dynamics and the evaporation rate are
      predicted using Blake's and Schrage's molecular kinetic models, respectively. An
      extensive grid independence study was conducted. Droplet impingement and
      evaporation data are acquired with a standard dispensing/imaging system and high
      speed photography. The numerical results are compared with measurements reported
      in the literature for millimeter-size droplets and with current microdroplet
      experiments in terms of instantaneous droplet shape and temporal spread (R/D(0)
      or R/R(E)), flatness ratio (H/D(0)), and height (H/H(E)) profiles, as well as
      temporal volume (inverted A) profile. The Weber numbers (We) for impinging
      droplets vary from 1.4 to 35.2 at nearly constant Ohnesorge number (Oh) of
      approximately 0.025-0.029. Both numerical and experimental results show that
      there is air bubble entrapment due to impingement. Numerical results indicate
      that Blake's formulation provides better results than the static (SCA) and
      dynamic contact angle (DCA) approach in terms of temporal evolution of R/D(0) and
      H/D(0) (especially at the initial stages of spreading) and equilibrium flatness
      ratio (H(E)/D(0)). Blake's contact line dynamics is dependent on the wetting
      parameter (K(W)). Both numerical and experimental results suggest that at 4.5 <
      We < 11.0 the short-time dynamics of microdroplet impingement corresponds to a
      transition regime between two different spreading regimes (i.e., for We < or =
      4.5, impingement is followed by spreading, then contact line pinning and then
      inertial oscillations, and for We > or = 11.0, impingement is followed by
      spreading, then recoiling, then contact line pinning and then inertial
      oscillations). Droplet evaporation can be satisfactorily modeled using the
      Schrage model, since it predicts both well-defined transient and quasi-steady
      evaporation stages. The model compares well with measurements in terms of
      flatness ratio (H/H(E)) before depinning occurs. Toroidal vortices are formed on
      the droplet surface in the gaseous phase due to buoyancy-induced Rayleigh-Taylor
      instability that enhances convection.

PMID- 20695570
TI  - Experimental and molecular simulation investigation of enhanced CO2 solubility in
      hybrid adsorbents.
AB  - Hybrid adsorbents are prepared by confining physical solvents (propylene
      carbonate, N-methyl-2-pyrrolidone) within the porosity of a solid support
      (alumina) using both wet and dry impregnation methods. The resulting hybrid
      solids are analyzed using characterization methods (N(2) adsorption isotherm,
      TGA) to ensure that a proper confinement of the solvent has been achieved. The
      hybrid adsorbents are then subsequently assessed for CO(2) capture by performing
      solubility measurements. An enhanced CO(2) solubility is observed with regard to
      the ones in the bulk solvent and in the raw solid. In a next step, grand
      canonical Monte Carlo simulations have been performed on a slit pore model to
      understand the microscopic mechanisms yielding the apparition of enhanced
      solubility. The presence of solvent molecules favors the layering of CO(2) within
      the pore, and the resulting local density profile is then markedly increased
      compared to one found in the raw adsorbent as more carbon dioxide molecules can
      be accommodated into the pore volume.

PMID- 20695571
TI  - Nanoscale limit to the applicability of Wenzel's equation.
AB  - We examine the extent to which nanoscale geometric substrate roughness influences
      the contact angle droplets establish on solid surfaces. Free-energy-based Monte
      Carlo simulation methods are used to compute contact angles and interfacial
      tensions of a model Lennard-Jones fluid on substrates with regular one
      dimensional heterogeneities characterized by amplitudes and periodicities in the
      2-25 nm range. We focus on a relatively strong surface that facilitates the
      formation of Wenzel droplets. Our results enable us to probe the validity of
      Wenzel's model at these length scales. We find that the aforementioned model
      predicts the evolution of the contact angle with near-quantitative accuracy over
      a wide range of amplitudes for substrates with periodicities larger than
      approximately 20 fluid diameters, or 10 nm for an argon-like system. However,
      below this length scale the Wenzel model provides progressively poorer estimates
      of the contact angle as the periodicity of the substrate features decreases. At
      these relatively small length scales, the Wenzel model overestimates the
      influence of roughness. To complete our analysis, we introduce a means to
      overcome sampling difficulties that arise at intermediate densities during grand
      canonical simulation. Specifically, we describe a two-step process that enables
      us to access the free energy of a system containing a thick liquid film in
      contact with the substrate. The process involves high-temperature grand canonical
      simulation followed by temperature-expanded ensemble simulation at relatively
      high surface density.

PMID- 20695572
TI  - Effect of dew condensation on the wettability of rough hydrophobic surfaces
      coated with two different silanes.
AB  - Dew condensation effects on the wettability of rough and smooth coatings of two
      fluoroalkylsilanes (FAS3 and FAS17) were investigated by controlling the
      temperature. Contact angles of the coatings decreased concomitantly with
      decreasing surface temperature. Inflection points in the temperature dependence
      of contact angles were observed at the dew point. They were attributable to the
      change of the interfacial free energy of the solid-gas interface by water
      adsorption. The contact angle decrease suggested a mode transition from Cassie to
      Wenzel on the rough surface, and resulted from the surface wettability change and
      the increase of the condensation amount of water. The contact angle change by
      increasing temperature from -6 degrees C revealed that the Wenzel mode is more
      stable than Cassie's mode.

PMID- 20695573
TI  - A microtensiometer to probe the effect of radius of curvature on surfactant
      transport to a spherical interface.
AB  - Diffusion of surfactant to a spherical interface depends on the radius of
      curvature of the interface; the smaller the radius of curvature is, the faster
      the dynamics. This paper presents and validates an experimental apparatus,
      denoted a "microtensiometer", to study the dependence of surfactant dynamics on
      radius of curvature. Dynamic surface tension is monitored for a range of bubble
      radii from 17 to 150 microm, and the dynamics are compared with those obtained
      using the classic pendant drop experiment for a nonionic surfactant at the air
      water interface. Experiments reveal that dynamic surface tension follows a
      diffusion-limited scaling, in which radius of curvature is a key parameter.
      Despite the clear scaling behavior of the experimental equilibration time, the
      full dynamic curve for an initially clean interface cannot be predicted by a
      diffusion-limited transport model using the molecular diffusion coefficient and a
      single isotherm. However, the same model is shown to correctly predict
      compression-expansion experiments. Aside from elucidation of surfactant
      transport, this device provides a tool for rapid measurements of interfacial
      properties using a significantly lower volume of sample than current methods.

PMID- 20695574
TI  - Adsorption and reactivity of 2,3-dihydrofuran and 2,5-dihydrofuran on Pd(111):
      influence of the C=C position on the reactivity of cyclic ethers.
AB  - High-resolution electron energy loss spectroscopy (HREELS) and temperature
      programmed desorption (TPD) were used to study the adsorption and thermal
      chemistry of 2,3-dihydrofuran (2,3-DHF) and 2,5-dihydrofuran (2,5-DHF) on
      Pd(111). The results, paired with earlier computational results, indicate that
      2,3-DHF and 2,5-DHF both adsorb on Pd(111) primarily via their respective olefin
      functional groups at low temperature (<170 K). Both molecules undergo
      dehydrogenation by 248 K to form species that produce furan in a reaction limited
      process above 300 K. The furan-producing intermediate intermediate can also
      undergo decomposition to form C(3)H(x) and CO. In addition, benzene resulting
      from C-C coupling reactions is detected on the surface and as a desorption
      product from both species, at about 520 K. A key difference between the two
      species is that 2,3-DHF can be hydrogenated to produce tetrahydrofuran at about
      330 K, whereas 2,5-DHF is more likely to dehydrogenate, producing furan in an
      additional low-temperature channel at approximately 320 K. The results point to
      the importance of the position of the olefin functional group in relation to the
      ether function in determining the reactivity of cyclic oxygenates.

PMID- 20695575
TI  - Methanol adsorption and decomposition on Pt/CeO2(111)/Cu(111) thin film model
      catalyst.
AB  - Adsorption and desorption of methanol on Pt particles on a CeO(2)(111)/Cu(111)
      thin film surface and on an ion-eroded Pt(111) single crystal were investigated
      by X-ray photoelectron spectroscopy and soft X-ray synchrotron radiation
      photoelectron spectroscopy (PES). Resonant PES was used to determine the
      occupancy of the Ce 4f states with high sensitivity. Multilayers of methanol were
      adsorbed at low temperature and subsequently desorbed by heating to 600 K.
      Methanol desorption is accompanied by the formation of chemisorbed methoxy 
      OCH(3). Cerium oxide surface is strongly reduced by methanol, which was detected
      via the transition Ce(4+) --> Ce(3+) and an increase of the Ce 4f electronic
      state occupancy. Partial C-O bond scission and formation of atomic carbon was
      observed on the Pt particles as well as on the rough Pt(111) surface. On
      Pt/CeO(2)(111), all traces of surface carbon and residual hydrocarbons disappear
      at 500 K.

PMID- 20695576
TI  - Spontaneous imbibition in nanopores of different roughness and wettability.
AB  - The spontaneous imbibition of liquid in nanopores of different roughness is
      investigated using coarse grain molecular dynamics (MD) simulation. The numerical
      model is presented and the simplifying assumptions are discussed in detail. The
      molecular-kinetic theory introduced by Blake is used to describe the effect of
      dynamic contact angle on fluid imbibition. The capillary roughness is modeled
      using a random distribution of coarse grained particles forming the wall. The
      Lucas-Washburn equation is used as a reference for analyzing the imbibition
      curves obtained by simulation. Due to the statistical nature of MD processing, a
      comprehensive approach was made to average and smooth the data to accurately
      define a contact angle. The results are discussed in terms of effective
      hydrodynamic and static capillary radii and their difference as a function of
      roughness and wettability.

PMID- 20695577
TI  - In situ STM imaging of fused thienothiopene molecules adsorbed on Au(111)
      electrode.
AB  - In situ scanning tunneling microscopy (STM) was used to reveal the structures of
      dithieno[2,3-b:3,2-d]thiophene diphenyl (DTT) molecules deposited onto Au(111)
      electrode from a dosing solution made of dichlorobenzene and 50 muM DTT.
      Potential control was proven to be of prime importance in guiding the arrangement
      of DTT admolecules on Au(111) in 0.1 M HClO(4), as disorder DTT adlayer seen at E
      > 0.3 V (vs reversible hydrogen electrode) was transformed into a highly ordered
      (2 x 7 square root(3))rect -2DTT structure when the potential was made to 0.05 to
      0.2 V. The ordered structure was stable for hours between 0.05 and 0.2 V.
      However, switching the potential further negative to 0 V resulted in slow melting
      of the ordered structure. The (2 x 7 square root(3))rect-DTT ordered adlattices
      recuperated when the potential was made positive to 0.2 V. Internal molecular
      functionalities of the thienothiophene and benzene in DTT admolecules were
      clearly discerned, from which the lateral structure for the (2 x 7 square
      root(3))rect-2DTT structure and registries of admolecules were deduced. The
      dynamics of the DTT adlattices on the Au(111) electrode surface was examined by
      real-time STM imaging, showing reorientation of as many as 150 DTT admolecules to
      join a neighboring ordered array within minutes.

PMID- 20695578
TI  - Equilibria of phosphatidylcholine-Ca2+ ions in monolayer at the air/water
      interface.
AB  - The effect of Ca(2+) ion interaction with monolayers of phosphatidylcholine
      (lecithin, L) was investigated at the air/water interface. We present surface
      tension measurements of lecithin monolayers obtained using a Langmuir method as a
      function of Ca(2+) ion concentration. The measurements were carried out at 22
      degrees C using a Teflon trough and a Nima 9000 tensiometer. The interactions
      between lecithin and Ca(2+) ions result in significant deviations from the
      additivity rule. An equilibrium theory to describe the behavior of monolayer
      components at the air/water interface was developed in order to obtain the
      stability constants and area occupied by one molecule of LCa(+) and L(2)Ca
      complexes. The stability constants, K(1) = 1.92 x 10(3) m(2) mol(-1) and K(2) =
      5.35 x 10(5) m(2) mol(-1) were calculated by inserting the experimental data. The
      value of area occupied by one LCa(+) complex is 65 A(2) molecule(-1), while the
      area occupied by an L(2)Ca complex is 117 A(2) molecule(-1).

PMID- 20695579
TI  - Single molecule observations of multiple protein populations at the oil-water
      interface.
AB  - Single-molecule total internal reflectance fluorescence microscopy was used to
      observe the dynamic behavior of >4000 bovine serum albumin objects at the
      silicone oil-water interface. The surface residence time distribution indicated
      the presence of three populations at the interface. Each population had a
      characteristic fluorescence intensity and distinctive interfacial diffusion
      behavior. Larger fluorescence intensity correlated with longer residence times
      and slower diffusion. These combined observations of fluorescence intensity,
      surface residence time, and interfacial diffusion suggested that the three
      populations represent monomers, dimers, and trimers respectively.

PMID- 20695580
TI  - Thin liquid crystal films on liquids in the nematic range of temperatures.
AB  - Hybrid nematic films deposited on liquid substrates reveal a complex behavior,
      which is not fully understood. Here, the behavior of the n-cyanobiphenyl series
      on water and glycerol has been studied in a wide temperature range, including the
      vicinity of the nematic-isotropic (NI) transition. Wettability, allowed film
      thicknesses, and line tension of nematic domains have been investigated. The
      study provides a coherent picture of hybrid nematic films, allowing us to account
      for lower thickness threshold, structure of the film edge, and line tension of
      domains in the whole nematic range of temperatures.

PMID- 20695581
TI  - Effect of vesicle size on the prodan fluorescence in
      diheptadecanoylphosphatidylcholine bilayer membrane under atmospheric and high
      pressures.
AB  - The bilayer phase behavior of diheptadecanoylphosphatidylcholine (C17PC) with
      different vesicle sizes (large multilamellar vesicle (LMV) and giant
      multilamellar vesicle (GMV)) was investigated by fluorescence spectroscopy using
      a polarity-sensitive fluorescent probe Prodan under atmospheric and high
      pressures. The difference in phase transitions and thermodynamic quantities of
      the transition was hardly observed between LMV and GMV used here. On the
      contrary, the Prodan fluorescence in the bilayer membranes changed depending on
      the size of vesicles as well as on the phase states. From the second derivative
      of fluorescence spectra, the three-dimensional image plots in which we can see
      the location of Prodan in the bilayer membrane as blue valleys were constructed
      for LMV and GMV under atmospheric pressure. The following characteristic behavior
      was found: (1) the Prodan molecules in GMV can be distributed to not only
      adjacent glycerol backbone region, but also near bulk-water region in the
      lamellar gel or ripple gel phase; (2) the blue valleys of GMV became deeper than
      those of LMV because of the greater surface density of the Prodan molecules per
      unit area of GMV than LMV; (3) the liquid crystalline phase of the bilayer
      excludes the Prodan molecules to a more hydrophilic region at the membrane
      surface with an increase in vesicle size; (4) the accurate information as to the
      phase transitions is gradually lost with increasing vesicle size. Under the high
      pressure condition, the difference in Prodan fluorescence between LMV and GMV was
      essentially the same as the difference under atmospheric pressure except for the
      existence of the pressure-induced interdigitated gel phase. Further, we found
      that Prodan fluorescence spectra in the interdigitated gel phase were especially
      affected by the size of vesicles. This study revealed that the Prodan molecules
      can move around the headgroup region by responding not only to the phase state
      but also to the vesicle size, and they become a useful membrane probe, detecting
      important membrane properties such as the packing stress.

PMID- 20695582
TI  - Biomimetic synthesis of multilayered aragonite aggregates using alginate as
      crystal growth modifier.
AB  - Polysaccharides were believed to play an important role in the mineralization
      process of many organisms. As the source of continuously and uniformly releasing
      alginate molecules and Ca(2+), alginate/Ca nanospherical gel was employed in the
      solution to induce the nucleation and growth of CaCO(3). Time-resolved
      transmission electron microscopy (TEM) was applied to study the crystallization
      at a very early stage. It was found that the initially formed lens-like vaterite
      particles gradually dissolved from the middle of the particle and released
      alginate molecules and Ca(2+) back into the system. As reaction time increased,
      the released substances were involved in the next stage of crystallization of
      CaCO(3), in the form of needle-like and shuttle-like aragonite particles
      sequentially depending on the concentration of alginate molecules and Ca(2+).
      "Egg-box" conformation of alginate and Ca(2+) was considered a skeleton for the
      growth of such aragonite particles. Notably, shuttle-like aragonite particles
      were composed of "bricks" of several hundred nanometers in size, which were very
      similar to biogenetic nacreous layers in shells.

PMID- 20695583
TI  - Influence of chain length on the diffusion and electrophoresis of DNA adsorbed on
      heterogeneous supported lipid bilayers.
AB  - This manuscript describes the influence of chain length on the diffusion and
      electrophoresis of single stranded DNA (ssDNA) adsorbed on heterogeneous cationic
      supported lipid bilayers. These studies are motivated by the increasing interest
      in developing novel strategies for the separation of DNA. We studied ssDNA
      molecules with the number of bases (N) varying from 21 to 84. Fluorescence
      recovery after photobleaching (FRAP) studies revealed that the diffusivity (D) of
      adsorbed ssDNA varied with N as D approximately N(-1), similar to a trend
      previously observed for the diffusion of double stranded DNA on homogeneous
      supported lipid bilayers. In contrast, the electrophoretic mobility of the
      adsorbed ssDNA in the presence of an applied tangential electric field was
      independent of N. Our studies indicated that the motion of ssDNA in the presence
      of an applied electric field was primarily due to electrophoresis and was not
      influenced significantly by electro-osmotic flow. Our results also suggest that
      the use of asymmetric diffusion barriers or other tunable obstacles may assist
      DNA separation on supported lipid bilayers.

PMID- 20695584
TI  - Photosynthetic electron transfer from reaction center pigment-protein complex in
      silica nanopores.
AB  - A photosynthetic reaction center (RC) pigment-protein complex purified from a
      thermophilic purple photosynthetic bacterium, Thermochromatium tepidum, was
      adsorbed to a folded-sheet silica mesoporous material (FSM). The RC has a
      molecular structure with a 7.0 x 5.0 x 13 nm diameter. The amount of RC adsorbed
      to the FSM compound with an average internal pore diameter of 7.9 nm (FSM(7.9))
      was high at 0.29 gRC/gFSM, while that to the FSM(2.7) (2.7 nm diameter) was low
      at 0.02 gRC/gFSM, suggesting the specific binding of the RC into the 7.9 nm pores
      of FSM(7.9). An N(2)-adsorption isotherm study indicated the incorporation of the
      RC into the 7.9 nm pores. The RC inside FSM(7.9) showed absorption spectra in the
      visible and infrared regions similar to those of the RC in solution, indicating
      almost no structural changes induced by the adsorption. The RC-FSM(7.9) conjugate
      showed the high photochemical activity with the increased thermal stability up to
      50 degrees C in the measurements by laser spectroscopy. The conjugates rapidly
      provided electrons to a dye in the outer medium or showed electric current on the
      ITO electrode upon the illumination. The RC-FSM conjugate will be useful for the
      construction of artificial photosynthetic systems and new photodevices.

PMID- 20695585
TI  - Structure and dynamics of cholic acid and dodecylphosphocholine-cholic acid
      aggregates.
AB  - Bile acids are powerful detergents that emulsify and solubilize lipids, vitamins,
      cholesterol and other molecules in the biliary tract and intestines. It has long
      been known that bile acids form soluble mixed micelles with lipids. However, the
      detailed thermodynamic and structural properties of these micelles are not fully
      understood. This study sheds light on this issue based on results from multiple
      molecular dynamics simulations of cholic acid (CA) and dodecylphosphocholine
      (DPC) mixed micelles. We found that CA molecules form aggregates of up to 12
      monomers with a mean size of 5-6. In agreement with several previous simulations
      and earlier predictions, the overall shape of these CA clusters is oblate disk
      like such that the methyl groups point toward the core of the aggregate and the
      hydroxyl groups point away from it. The self-aggregation behavior of the CA
      clusters in the DPC-CA mixture is similar to the pure CA. Furthermore, the sizes
      and aggregation numbers of the DPC-CA mixed micelles are linearly dependent on CA
      molarity. In agreement with the radial shell model of Nichols and Ozarowski
      [Nichols, J. W.; Ozarowski, J. Biochemistry 1990, 29, 4600], our results
      demonstrate that CA molecules form a wedge between the DPC molecules with their
      hydroxyl and carboxyl groups facing the aqueous phase while their methyl groups
      are buried in and face the hydrocarbon core of the DPC micelle. The DPC-CA
      micelles simulated here tend to be spherical to prolate in shape, with the
      deviation from spherical geometry significantly increasing with increasing CA:DPC
      ratio.

PMID- 20695586
TI  - 1,2,3-Triazole-containing molecular pockets derived from cholic acid: the
      influence of structure on host-guest coordination properties.
AB  - Two cholic acid-containing trimers with 1,2,3-triazole groups close to the
      connecting point ("top") and at the end of the cholic acid arms ("bottom") were
      synthesized. These molecules are able to form hydrophobic pockets and solubilize
      pyrene and other hydrophobic molecules in polar media due to the facial
      amphiphilicity of cholic acid. Heavy metal ions such as Cu(II) can also be
      coordinated by the 1,2,3-triazole groups, as shown by EPR spectroscopy. Due to
      the vicinity of metal ions and pyrene in the pockets, the fluorescence of pyrene
      is quenched. However, the position of the 1,2,3-triazole groups has a crucial
      influence on the metal ion complexation. The trimer with 1,2,3-triazole groups at
      the top is found to bind metal ions more effectively and gives rise to a
      significantly enhanced fluorescence quenching efficiency. Here, the metal ions
      act as one tridentate chelating agent, while the triazoles on the bottom rather
      behave as single entities without any cooperativity in binding to the metal. In
      the latter case, the quenching effect is reduced considerably despite the fact
      that both trimers are able to bind Cu(II). This indicates that the specific and
      strong binding of Cu(II) at the top leads to closer spatial proximity between
      metal ion and pyrene when compared to the Cu(II) bound on the bottom.

PMID- 20695587
TI  - Formation of silica precipitates on membrane surfaces in two and three
      dimensions.
AB  - Ether lipids with alkyl chains of uniform length and varying amine headgroups
      were synthesized and assembled into bilayer structures in aqueous solution, which
      served as templates for the formation of silica in two and three dimensions
      produced under ambient conditions. Dynamic light scattering revealed that
      unilamellar vesicles of the aminolipids are formed by the extrusion method. The
      alkylation of the polar amine headgroup was systematically increased from a
      primary, secondary, and tertiary amine to a quaternary ammonium salt, and the
      amount of silica was quantified by the beta-silicomolybdate method as a function
      of the headgroup. A lysinol-connected ether lipid harboring two primary amine
      groups was also investigated. This variation enabled us to compare the influence
      of the headgroup on the properties of the precipitated silica in detail. By
      spreading of unilamellar aminolipid vesicles onto planar silicon substrates, two
      dimensional planar bilayers can be produced. By means of ellipsometry in
      conjunction with atomic force microscopy, we were able to demonstrate that very
      thin silica layers with a thickness of a few nanometers are formed within minutes
      on the surface of the aminolipid bilayers. All layers are composed of silica
      nanospheres, and the thickness turned out to be independent of the amine
      headgroup.

PMID- 20695588
TI  - Effect of urea and glycerol on the adsorption of ribonuclease A at the air-water
      interface.
AB  - This study reports on the influence of nonionic cosolvents on the interfacial
      structure of ribonuclease A (RNase) adsorbed at the air-water interface. We
      applied X-ray reflectometry to obtain detailed volume fraction profiles of the
      adsorbed layers and to follow the effect of glycerol and urea on the adsorbate
      structure as a function of cosolvent concentration. Under all conditions studied,
      the adsorbed RNase layer maintains its compact shape, and the adsorbed RNase
      molecules adopt a flat-on orientation at the interface. Both kosmotropic glycerol
      and chaotropic urea exert profound effects on the adsorbate: The surface excess
      decreases linearly with glycerol content and is also reduced at low urea
      concentration. However, at high urea concentration, parts of the adsorbed layer
      are dehydrated and become exposed to air. The electron density and volume
      fraction profiles of the adsorbed protein provide clear evidence that these
      effects are ruled by different mechanisms.

PMID- 20695590
TI  - Ce:YAG nanoparticles embedded in a PMMA matrix: preparation and characterization.
AB  - A Ce:YAG-poly(methyl methacrylate) composite was prepared using in situ
      polymerization by embedding the Ce:YAG nanopowder in a blend of methyl
      methacrylate (MMA) and 2-methacrylic acid (MAA) monomers and activating the
      photopolymerization using a radical initiator. The obtained nanocomposite was
      yellow and transparent. Its characterization was performed using transmission
      electron microscopy, small angle X-ray scattering, (13)C cross-polarization magic
      angle spinning nuclear magnetic resonance, and photoluminescence spectroscopy.
      Results showed that Ce:YAG nanoparticles are well dispersed in the polymeric
      matrix whose structure is organized in a lamellar shape. The luminescence
      properties of the nanocomposite do not show quenching or a significant spectral
      shift, indicating that the nanocomposite can be useful for advanced applications
      such as white LED construction.

PMID- 20695589
TI  - Microfluidic fabrication of hydrogel microparticles containing functionalized
      viral nanotemplates.
AB  - We demonstrate rapid microfluidic fabrication of hybrid microparticles composed
      of functionalized viral nanotemplates directly embedded in polymeric hydrogels.
      Specifically, genetically modified tobacco mosaic virus (TMV) templates were
      covalently labeled with fluorescent markers or metalized with palladium (Pd)
      nanoparticles (Pd-TMV) and then suspended in a poly(ethylene glycol)-based
      solution. Upon formation in a flow-focusing device, droplets were
      photopolymerized with UV light to form microparticles. Fluorescence and confocal
      microscopy images of microparticles containing fluorescently labeled TMV show
      uniform distribution of TMV nanotemplates throughout the microparticles.
      Catalytic activity, via the dichromate reduction reaction, is also demonstrated
      with microparticles containing Pd-TMV complexes. Additionally, Janus
      microparticles were fabricated containing viruses embedded in one side and
      magnetic nanoparticles in the other, which enabled simple separation from bulk
      solution. These results represent a facile route to directly harness the
      advantages of viral nanotemplates into a readily usable and stable 3D assembled
      format.

PMID- 20695591
TI  - Surface grafting of cellulose nanocrystals with poly(ethylene oxide) in aqueous
      media.
AB  - Aqueous suspensions of poly(ethylene oxide)-grafted nanocrystalline cellulose
      (PEO-grafted NCC) were prepared in order to achieve steric instead of
      electrostatic stabilization. A two-step process was employed: in the first step
      NCC suspensions prepared by sulfuric acid hydrolysis were desulfated with sodium
      hydroxide, and in the second step the surfaces of the crystals were
      functionalized with epoxy-terminated poly(ethylene oxide) (PEO epoxide) under
      alkaline conditions. The PEO-grafted samples were analyzed by conductometric
      titration, ATR-IR, solid-state NMR, MALDI-TOF MS, SEC MALLS, and AFM. The
      covalent nature of the linkage was confirmed by weight increase and MALDI-TOF
      analysis. The PEO-grafted cellulose nanocrystals (CNCs) formed a stable colloidal
      suspension that remained well dispersed, while the desulfated nanoparticles
      aggregated and precipitated. Upon concentration of the PEO-grafted aqueous NCC
      suspension, a chiral nematic phase was observed.

PMID- 20695592
TI  - Effect of molecular structure on the properties of naphthalene-dipeptide
      hydrogelators.
AB  - Dipeptide-conjugates can be efficient low molecular weight hydrogelators.
      However, the effective design of a gelator for a specific application is
      compromised by the lack of a clear understanding of the design rules that govern
      assembly and hence gelation. Here, we report a library of naphthalene-dipeptides,
      their physical chemical properties, and gelation ability. We have varied both the
      amino acids in the dipeptides and the substitution on the naphthalene ring to
      allow variation of the structure throughout the molecule. We have examined the
      effects of these permutations on the critical micelle concentration and air-water
      partition coefficient at high pH and the apparent pK(a). We show that there is a
      clear link between these properties and the predicted hydrophobicity of the
      overall conjugates, rather than the properties varying with, for example, the
      dipeptide sequence. The majority of these dipeptide-conjugates are effective
      hydrogelators, although there is no apparent link between the solution properties
      and whether or not a conjugate is a hydrogelator. Nevertheless, where gelation
      occurs, the link between hydrophobicity and apparent pK(a) allows the prediction
      of the pH at which a gel will be formed and hence informed choice of gelator for
      specific applications.

PMID- 20695593
TI  - Fabrication and conductive properties of multilayered ultrathin films designed by
      layer-by-layer assembly of water-soluble fullerenes.
AB  - Fullerene ultrathin films were fabricated by layer-by-layer (LbL) assembly of an
      anionic fullerene C(61)(COO(-))(2) (FDCA) and poly(diallyldimethylammonium
      chloride) (PDDA) or a cationic fullerene C(60)C(2)H(4)N(CH(3))(2)(+) (FMAC) and
      poly(sodium 4-styrenesulfonate) (PSS). The dynamic light scattering and zeta
      potential measurements revealed that both water-soluble fullerenes are stably
      dispersed as polyelectrolytes with a diameter of 20-70 nm for FDCA and 60-180 nm
      for FMAC in aqueous solutions. In spite of such large fullerene aggregates, the
      thickness of fullerene LbL films increased regularly by a few nanometers with
      each deposition, and the resultant LbL films were homogeneous. For FMAC/PSS LbL
      films, the monolayer thickness was evaluated to be 4 nm for FMAC and 0.5 nm for
      the PSS layer. In other words, the volume fraction of the fullerene moiety is as
      high as approximately 80 vol %. The conductivity of fullerene LbL films was
      comparable to that of a C(60)-dispersed polystyrene film with a similar fullerene
      fraction, suggesting that there exist effective percolating networks due to the
      high fullerene fraction in the LbL films. The electron mobility of FMAC/PSS LbL
      films was as high as 3 x 10(-5) cm(2) V(-1) s(-1), which is comparable to the
      hole mobility of poly(p-phenylenevinylene) LbL films reported previously.

PMID- 20695594
TI  - Br(-)-induced facile fabrication of spongelike gold/amino acid nanocomposites and
      their applications in surface-enhanced Raman scattering.
AB  - We report a facile method for the fabrication of spongelike gold/amino acid
      nanocomposites by the addition of NaBr to glutamic acid-stabilized gold
      nanoparticles (GNPs) at room temperature. The gold/glutamic acid (Glu)
      nanocomposite is characterized by TEM, SEM, UV-vis spectroscopy, and XRD
      measurements. The results suggest that the three-dimensional spongelike gold/Glu
      nanocomposites with mean diameter of 50 nm are formed via the nanospheres fusing
      into one another. The driving force for the fabrication of spongelike gold/amino
      acid nanocomposites is the van der Waals attractive forces of Br(-) partially
      coated GNPs. Furthermore, the obtained spongelike gold nanocomposites can be used
      as surface-enhanced Raman scattering (SERS) substrates with high SERS activity
      and stability for detecting Rhodamine 6G (R6G) molecules. Hence, NaBr-mediated
      preparation of SERS substrates described in this work has potential applications
      in chemical and biological analysis as well as medical detection.

PMID- 20695595
TI  - Molecular design of near-IR harvesting unsymmetrical squaraine dyes.
AB  - The functionalized unsymmetrical benzothiazole squaraine organic sensitizers 5
      carboxy-2-({3-[(3-hexylbenzothiazol-2(3H)-ylidene)methyl]-2-hydroxy-4-oxo-2
      cyclobuten-1-ylidene}methyl)-1-hexyl-3,3-dimethyl-3H-indolium (hereafter named as
      SK-11) and 5-carboxy-2-({3-[(3-hexyl-5-methoxybenzothiazol-2(3H)-ylidene)methyl]
      2-hydroxy-4-oxo-2-cyclobuten-1-ylidene}methyl)-1-hexyl-3,3-dimethyl-3H-indolium
      (coded as SK-12) are designed and developed to observe an intense and wider
      absorption band in the red/NIR wavelength region. DFT/TDDFT calculations have
      been performed on the two unsymmetrical squaraine sensitizers to gain insight
      into their electronic and optical properties. The utility of these dyes in solid
      state dye sensitized solar cells (SS-DSSCs) is demonstrated.

PMID- 20695596
TI  - Accessibility control on copper(II) complexes in mesostructured porous silica
      obtained by direct synthesis using bidentate organosilane ligands.
AB  - The accessibility of metal(II) complexes in 2D hexagonal mesostructured porous
      silicas obtained by direct synthesis is controlled using an appropriate
      organosilane ligand. This is exemplified here using copper(II) as a transition
      metal probe and a neutral or negatively charged ligand: N-(2-aminoethyl)-3
      aminopropyltrimethoxysilane, L(A), and, N-salicylaldimine-propylamine
      trimethoxysilane, L(B)(-), respectively. L(A) leads to inaccessible complexes
      located into the pore wall and called "embedded" sites here where silanolate
      groups from the siliceous network block the access to Cu(II) ions. By contrast,
      L(B)(-) generates accessible complexes, named "showing-on" sites here. The copper
      containing silicas were synthesized with various metal molar ratios (M/SiO(2) =
      0.5-3%) in basic media, with cetyltrimethylammonium p-toluenesulfonate (CTATos)
      as template and with sodium silicate solution as silicon source. A soft template
      extraction procedure has been developed to preserve the complex integrity of the
      showing-on copper sites during the treatment. The embedded copper(II) and
      nickel(II) sites were compared. Materials containing embedded, showing-on, and
      grafted sites were also compared with regard to pore size, surface polarity, and
      metal leaching. The material containing showing-on sites was found to be
      catalytically active for the hydroxylation of phenol into catechol and
      hydroquinone. Both textural and structural properties of the material and the
      copper sites were investigated using XRD, TEM, N(2) sorption isotherms, TGA, FT
      IR, UV-visible, and EPR spectroscopies.

PMID- 20695597
TI  - Self-organization of particles with planar surface anchoring in a cholesteric
      liquid crystal.
AB  - We present birefringence and fluorescence confocal microscopy studies of melamine
      particles in a liquid-crystalline host solvent. The liquid crystal has a
      cholesteric phase at room temperature with a helical pitch that can be modified
      by changing the composition. The pitch employed here is always less than the
      particle diameter (3 microm). We demonstrate via birefringence that the mesogens
      preferentially anchor flat at the melamine surface. Via studies in a sample cell
      with aligning surfaces we show that although the particles form chains in a
      nematic liquid crystal they organize in 2D plates in a cholesteric. Fluorescence
      confocal microscopy and particle location analysis are used to determine the
      radial distribution function and to evaluate the particle aggregation number as a
      function of pitch length. We discuss possible explanations for the self
      organization.

PMID- 20695598
TI  - Potential-controlled electrochemical seed-mediated growth of gold nanorods
      directly on electrode surfaces.
AB  - Here we compare the amount and the morphology of Au nanostructures
      electrodeposited from a solution containing 2.5 x 10(-4) M AuCl(4)(-) and 0.1 M
      cetyltrimethylammonium bromide (CTAB) onto nonseeded and Au-nanoparticle (NP)
      seeded mercaptopropyltrimethoxysilane (MPTMS)-functionalized glass/indium tin
      oxide (glass/ITO) electrodes as a function of the electrode potential and
      deposition time. The method is similar to the previously reported seed-mediated
      chemical synthesis of Au nanorods (NRs) in solution and on surfaces, except that
      we replace the chemical reducing agent (ascorbic acid) with the electrochemical
      potential. The deposition can be classified into three different potential ranges
      on the nonseeded and seeded electrodes on the basis of the amount of Au deposited
      and the morphology of the deposited nanostructures. On the nonseeded
      glass/ITO/MPTMS electrode, at potentials ranging from -0.30 to -0.20 V, there are
      a significant number of Au deposits on the surface with mainly branched
      morphology. At deposition potentials ranging from -0.10 to 0.27 V, there is very
      little deposition of Au but the few deposits also have a branched morphology. At
      0.27 V and higher, there is no Au deposition on the glass/ITO/MPTMS electrode.
      Because Au seeds catalyze Au deposition, the three potential ranges, the amount
      of Au, and the morphologies are quite different on the glass/ITO/MPTMS/Au NP seed
      electrodes compared to those on the nonseeded glass/ITO/MPTMS electrodes. There
      is a significant amount of Au (more than on the nonseeded electrode) on the
      surface over a wider range of potentials from -0.30 to 0.27 V, and they have
      spherical morphology. From 0.30 to 0.35 V, less Au deposits on the electrode and
      there are 5-15% Au NRs on the surface in addition to spherical NPs. Above 0.35 V,
      there is no Au deposition on the glass/ITO/MPTMS/Au seed electrode. For
      depositions within the potential range of 0.30 to 0.35 V on glass/ITO/MPTMS/Au
      seed electrodes, the size and shape distributions of the Au nanostructures,
      including NRs, are similar to those previously synthesized by chemical seed
      mediated growth in solution and directly on nonconductive surfaces. The yield,
      length, and aspect ratio of the Au NRs depend on the deposition time; the average
      length ranges from about 100 to 400 nm for times of 30 to 120 min. The
      electrochemical seed-mediated growth of Au is optimal from 0.30 to 0.35 V versus
      Ag/AgCl under our conditions, which could be useful for enhancing the signal in
      sensing strategies that employ Au NPs as optical or electrochemical tags.

PMID- 20695599
TI  - Characterization of flowerlike silicon particles obtained from chemical etching:
      visible fluorescence and superhydrophobicity.
AB  - Flowerlike silicon particles are obtained by chemical etching of polycrystalline
      silicon polyhedrons using a mixture of hydrofluoric acid and nitric acid. The
      etched flowerlike particles show stable bright red photoluminescence under UV
      irradiation. The formation of pores with diameters of 3, 5.5, and 20 nm is
      revealed during etching. The etched particles exhibit superhydrophobic behavior
      with a contact angle of 158 degrees because of the sharp tips of their "petals".
      The source silicon polyhedrons are shown to possess radial grain boundaries.
      Preferential etching along the radial grain boundaries of the polyhedrons is
      thought to be the key reason for the formation of flowerlike porous silicon
      particles.

PMID- 20695600
TI  - Self-cleaning antireflective coatings assembled from peculiar mesoporous silica
      nanoparticles.
AB  - Novel mesoporous silica nanoparticles of peculiar shapes were synthesized, from
      which hierarchically porous silica coatings were fabricated on glass substrates
      via layer-by-layer (LbL) assembly, followed by calcination. These porous silica
      coatings were highly transparent and superhydrophilic. The maximum transmittance
      reached as high as 94%, whereas that of the glass substrate is 91%. The time for
      a droplet to spread lower than 5 degrees decreased to as short as 0.25 s. After
      the coating surface was treated with a low surface energy material, the surface
      became superhydrophobic (water contract angle >150 degrees) with a very low
      sliding angle of <1 degree. Compared with MCM-41-type mesoporous silica
      nanoparticles, the coatings fabricated using the novel mesoporous silica
      nanoparticles possess much better self-cleaning property. We used scanning (SEM)
      and transmission (TEM) electron microscopy to observe the morphology and
      structure of nanoparticles and surfaces. Transmission spectra and their change
      with time were characterized by UV-vis spectrophotometer. We studied the surface
      wettability by a contact angle/interface system. The influence of mesopores on
      the transmittance and wetting properties of coatings was discussed on the basis
      of experimental observations.

PMID- 20695601
TI  - Biomineralization of gold nanoparticles by lysozyme and cytochrome C and their
      applications in protein film formation.
AB  - Lysozyme (Lys) and cytochrome c (Cyc,c) proteins were used as mild reducing and
      stabilizing agents to synthesize gold nanoparticles (NPs) at precisely 40 and 80
      degrees C. All reactions were monitored simultaneously by UV-visible measurements
      to determine changes in the nature of the protein during the course of reaction.
      The synthesis of Au NPs caused the simultaneous denaturation of protein due to
      the formation of bioconjugate NPs, and the denaturation temperature decreased
      with the number of NPs. Lys entrapped NPs in a typical gel state, and Cyc,c
      carried them on well-defined micelles at 80 degrees C or in the form of long
      fibrils or strands at 40 degrees C. The shape, size, and arrangement of
      bioconjugate NPs were characterized by atomic force microscopy and transmission
      electron microscopy measurements. Purified bioconjugate NPs were further used in
      zein protein film formation. The resulting films were characterized by
      photophysical and mechanical measurements. The induction of bioconjugate NPs made
      protein films isotropic and relatively more brittle (with a greater effect for
      Cyc,c than for Lys conjugate NPs) than in their absence and was considered to be
      well suited for biomedical applications.

PMID- 20695602
TI  - Connector ability to design superhydrophobic and oleophobic surfaces from
      conducting polymers.
AB  - In the aim of creating superoleophobic surfaces using monomers with short
      perfluorinated chains, to avoid drawbacks associated with PFOA, original
      semifluorinated (C(4)F(9), C(6)F(13)) 3,4-ethylenedioxypyrrole derivatives were
      synthesized. These monomers were obtained using the faster synthetic method than
      previously described with some analogues, characterized and electrochemically
      polymerized on gold plates. The obtained surfaces exhibited superhydrophobic
      (contact angle with water of 157 degrees and 158 degrees, respectively) and
      oleophobic properties (contact angle with hexadecane: 88 degrees and 108 degrees,
      respectively). The comparison between these new monomers and already published
      analogue EDOP6 confirms the importance of the bipolaronic form of conductive
      polymer for obtaining surface nanoporosity and as a consequence improving surface
      oleophobicity. Thus, little change in the molecule design of the connector and
      the spacer of the monomer can have a significant influence on the surface
      oleophobicity.

PMID- 20695603
TI  - Substrate effects on the wettability of electrospun titania
      poly(vinylpyrrolidone) fiber mats.
AB  - Titania-poly(vinylpyrrolidone) (PVP) core-shell nano/microfibers are electrospun
      on substrates of differing hydrophilicity and conductivity in order to
      investigate the connection between these substrate properties and the apparent
      water contact angles against the fiber mats. The focus of this study compares
      current data from silicon- and aluminum foil-supported mats to extant data from
      ITO and glass-supported fibers to detail the complexities of apparent contact
      angle dependence on mat structure related to substrate properties.
      Electrospinning time and collection distance were controlled parameters for
      producing thicker and denser mats. In all cases, contact angles increased with
      collection time for a given substrate series. A morphological wettability study
      of the fiber mat surface was conducted by applying Rhodamine B dye solution
      droplets. Using fluorescence microscopy, the stained fibers indicate the extent
      of true wetting contact and the lack of penetration into the fiber layers. Image
      comparisons with bright-field illumination confirms that even some fibers of the
      top layers are not wetted.

PMID- 20695604
TI  - One-step synthesis of monodisperse and hierarchically mesostructured silica
      particles with a thin shell.
AB  - Monodisperse, uniform, and hierarchically mesostructured silica particles with a
      thin shell have been fabricated via one-step synthesis using dodecanethiol (C(12)
      SH) and CTAB as dual templates. A series of hierarchically mesostructured silica
      particles with a morphology similar to that of pomegranate can be obtained by
      simply adjusting the mass ratio of C(12)-SH to CTAB. When the mass ratio is
      increased, a mesophase transformation occurs from an ordered 2D hexagonal
      structure to a mesostructured cellular foam in the core of the hierarchically
      mesoporous silica particles. These unique silica particles are characterized by
      small-angle X-ray diffraction (XRD), scanning electron microscopy (SEM),
      transmission electron microscopy (TEM) and energy dispersive spectroscopy (EDS),
      Fourier transform infrared spectroscopy (FT-IR), and nitrogen adsorption
      desorption measurements. The formation mechanism of the hierarchically
      mesostructured silica particles with a thin shell is proposed according to the
      experimental results. Synergistic self-assembly of C(12)-SH and CTAB in the
      solution is believed to play a key role in mediating the formation of these
      hierarchical silica mesostructures, and the hydrophobic dodecanethiol can act as
      both the swelling agent for CTAB micelles and coagent for the formation of a
      microemulsion with CTAB micelles. This synthesis method is simple,
      straightforward, and suitable for the preparation of the other biomineral
      nanostructures that are unique scaffolds in biological, medical, and catalytic
      applications.

PMID- 20695605
TI  - Facile route to morphologically tailored silver patches on colloidal particles.
AB  - Here we demonstrate, for the first time, the heterogeneous nucleation and growth
      of silver patches on submicrometer silica spheres. While patches can be grown
      directly onto native silica particles, it is shown that a higher patch yield can
      be obtained by first treating the silica with a mixture of an alkanolamine and
      silver nitrate. Variation of the pretreatment and subsequent coating reactions
      allowed the patch yield, number, size, thickness, and shape to be adjusted. The
      patchy particles were shown to possess plasmon modes extending from the visible
      into the near-IR region, making these structures highly interesting for both
      their asymmetric morphological and functional properties.

PMID- 20695606
TI  - Nonaligned carbon nanotubes partially embedded in polymer matrixes: a novel route
      to superhydrophobic conductive surfaces.
AB  - A new method for transforming common polymers into superhydrophobic conductive
      surfaces, with both a high static water contact angle (approximately 160 degrees)
      and a low sliding angle (2.0 degrees-4.5 degrees), and a low sheet resistance on
      the order of 10(1)-10(3) ohms/sq is presented. A layer of multiwalled carbon
      nanotubes (MWNTs) is first distributed on the surface of a polymer substrate,
      then by a single step of pressing, the MWNTs are partially embedded inside the
      substrate surface and form a superhydrophobic coating with a "carpet-" or "hair"
      like morphology. The infiltration of polymer melts into the porous MWNT layer
      follows Darcy's law, and the pressing time greatly influence the morphology and
      superhydrophobicity. Moreover, the coating can be electrically heated by 20-70
      degrees C with a voltage as low as 4-8 V at an electric energy density below 1.6
      J/cm(2) and therefore can be used for deicing applications. Hydroxylation and
      fluoroalkylsilane treatment can greatly improve the stability of the
      superhydrophobicity of MWNTs. This method is convenient and applicable to a
      variety of thermoplastic polymers and nonpolymer substrates coated by silicone
      rubber.

PMID- 20695607
TI  - On the water dispersibility of a 1:1 stoichiometric complex between a cationic
      nanogel and linear polyanion.
AB  - This work aimed to obtain information on the water dispersibility of a 1:1
      stoichiometric polyelectrolyte nanogel complex (SPENC). We synthesized a cationic
      polyelectrolyte nanogel (CPENG) composed of a cross-linked copolymer of 1
      vinylimidazole and N-isopropylacrylamide. SPENC was then prepared at 25 degrees C
      from the mixing of equimolar amounts (based on fixed charges) of CPENG and
      potassium poly(vinyl alcohol) sulfate, which were dissolved in an aqueous
      solution without adding salt and at pH 3.0. We carefully observed at 25 degrees C
      the reduction of the imidazole-based cationic charge in the CPENG component of
      SPENC as a function of pH. Dynamic and static light scattering techniques were
      employed in combination with electrophoretic light scattering experiments. The
      amount of cationic charge in the SPENC was estimated from the potentiometric
      titration data of CPENG. It was found that, during the charge reduction process,
      the complex underwent aggregation, followed by a phase separation. The
      aggregation started at about 25% of the charge reduction (i.e., at pH
      approximately = 4.9), and the phase separation took place when almost half of the
      charge was eliminated (at pH approximately = 5.5). However, the phase-separated
      complexes became water-soluble again when about 90% of the charge was eliminated
      (pH approximately = 6.6). By colloid titration, the dissociated free polyanions
      were not detected in the aqueous SPENC solution before the phase separation but
      were detected in the complex-redispersed solution. When the pH (9.0) of the
      redispersion was slowly decreased to the original level (pH 3.0) by the gradual
      addition of HCl so as to cause again the phase separation, an intraparticle
      complex was reformed, the physical quantities of which were close to those of the
      initial SPENC. These findings clearly indicate that the whole and a part
      (segment) of the complexed polyanions undergoes dissociation-association
      reactions on the surface of a SPENC particle, depending on the ionization state
      of the cationic gel component. As a result, these reactions seem to be a key
      factor for the water dispersibility of the SPENC.

PMID- 20695608
TI  - Enzymatic activity of lipase-nanoparticle conjugates and the digestion of lipid
      liquid crystalline assemblies.
AB  - Variants of lipase were attached to gold nanoparticles (NPs) and their enzymatic
      activity was studied. The two bioengineered lipase variants have been prepared
      with biotin groups attached to different residues on the protein outer surface.
      The biotinylation was evidenced by denaturing polyacrylamide gel electrophoresis
      and quantified by the ([2-(4'-hydroxyazobenzene)]benzoic acid spectrophotometric
      test. NPs of 14 +/- 1 nm diameter coated with thiolated-polyethylene glycol
      ligands containing controlled proportions of biotin moieties have been prepared
      and characterized by transmission electron microscopy, UV-vis spectroscopy, small
      angle neutron scattering, and elemental analysis. These biotin-functionalized NPs
      were conjugated to lipase using streptavidin as a linker molecule. Enzyme
      activity assays on the lipase-nanoparticle conjugates show that the lipase
      loading and activity of the NPs can be controlled by varying the percentage of
      biotin groups in the particle protecting coat. The lipase-NP conjugates prepared
      using one variant display higher activity than those prepared using the other
      variant, demonstrating orientation-dependent enzyme activity. Cryogenic
      transmission electron microscopy was used to visualize the enzymatic activity of
      lipase-NP on well-defined lipid substrates. It was found that lipase-coated NPs
      are able to digest the substrates in a different manner in comparison to the free
      lipase.

PMID- 20695609
TI  - Large-area nanopatterning of self-assembled monolayers of alkanethiolates by
      interferometric lithography.
AB  - We demonstrate that interferometric lithography provides a fast, simple approach
      to the production of patterns in self-assembled monolayers (SAMs) with high
      resolution over square centimeter areas. As a proof of principle, two-beam
      interference patterns, formed using light from a frequency-doubled argon ion
      laser (244 nm), were used to pattern methyl-terminated SAMs on gold, facilitating
      the introduction of hydroxyl-terminated adsorbates and yielding patterns of
      surface free energy with a pitch of ca. 200 nm. The photopatterning of SAMs on Pd
      has been demonstrated for the first time, with interferometric exposure yielding
      patterns of surface free energy with similar features sizes to those obtained on
      gold. Gold nanostructures were formed by exposing SAMs to UV interference
      patterns and then immersing the samples in an ethanolic solution of
      mercaptoethylamine, which etched the metal substrate in exposed areas while
      unoxidized thiols acted as a resist and protected the metal from dissolution.
      Macroscopically extended gold nanowires were fabricated using single exposures
      and arrays of 66 nm gold dots at 180 nm centers were formed using orthogonal
      exposures in a fast, simple process. Exposure of oligo(ethylene glycol)
      terminated SAMs to UV light caused photodegradation of the protein-resistant tail
      groups in a substrate-independent process. In contrast to many protein patterning
      methods, which utilize multiple steps to control surface binding, this single
      step process introduced aldehyde functional groups to the SAM surface at
      exposures as low as 0.3 J cm(-2), significantly less than the exposure required
      for oxidation of the thiol headgroup. Although interferometric methods rely upon
      a continuous gradient of exposure, it was possible to fabricate well-defined
      protein nanostructures by the introduction of aldehyde groups and removal of
      protein resistance in nanoscopic regions. Macroscopically extended,
      nanostructured assemblies of streptavidin were formed. Retention of functionality
      in the patterned materials was demonstrated by binding of biotinylated proteins.

PMID- 20695610
TI  - Water properties in a novel thermoswelling poly(vinyl alcohol) derivative
      hydrogel as studied by nuclear magnetic resonance and Fourier transform infrared
      spectroscopy.
AB  - Water properties in a novel thermoswelling hydrogel, which was prepared from
      poly(vinyl alcohol)-trimellitate (PVA-T) by a simple chemical cross-linking and
      swollen in 0.1-1.0 M Li(2)SO(4) solutions, were investigated through nuclear
      magnetic resonance and Fourier transform infrared (FTIR) spectroscopies. The spin
      spin relaxation of the water proton in the hydrogel was measured at 5-35 degrees
      C, and the results were analyzed with a two-component model to obtain a long T(2)
      and a short T(2) as well as their fractions (f(short) = 1 - f(long)). The
      f(short) values thus obtained proved to be a linear function of the gel swelling
      ratio, and all of the data, except for an upper deviation at 1.0 M Li(2)SO(4),
      were found to be on an almost same line irrespective of the temperature and the
      salt concentration. This dependency of f(short) on the swelling degree strongly
      suggests that the temperature increment has an equivalent effect as that of the
      SO(4)(2-) concentration; namely, scission of inter(intra-)molecular hydrogen
      bonding (HB) between the COOHs on the side group must be responsible for the
      observed thermoswelling in the sulfate salt solutions. The upper deviation of
      f(short) at 1.0 M from the "master line" was reasonably interpreted in terms of
      the salting-out effect by the concentrated sulfate anion. On the other hand,
      attenuated total reflection-FTIR measurements for a gel plate revealed that an
      appreciable dissociation of the carboxyl group occurred only in the 1.0 M
      Li(2)SO(4) system. This finding, in turn, means that gel swelling with an
      increase in the salt concentration up to 0.5 M is not caused by the ionization of
      the gel and supports the scission of the intermolecular HB. Hydrophobic hydration
      around the main chain was investigated via a peak shift of the stretching
      vibration of -CH(2)-, and the slight red shift observed only at 1.0 M suggested
      that the salting-out effect onto the hydrophobic hydration is rather limited and
      the hydration around the main chain still remained even with the significant
      deswelling at 1.0 M.

PMID- 20695611
TI  - Structures and phase behavior in mixtures of charged colloidal spheres and
      platelets.
AB  - The experimental phase diagram for aqueous mixtures of charged gibbsite platelets
      and silica spheres is presented. The platelets are 95 nm in diameter, and the
      diameter ratio between the spheres and the platelets is 0.18. Here the spheres
      are acting as depletants in the mixtures perturbing the phase behavior of the
      pure platelet suspensions. An important finding is that a large
      isotropic/columnar coexistence region has been identified in the phase diagram,
      which appeared already at low concentrations of the platelets. Microradian X-ray
      diffraction measurements revealed the structure of the liquid crystalline phases
      and the orientational order of platelets. An interesting observation is that in
      the columnar phase the silica spheres are located between the columnar stacks.
      All samples were in equilibrium because sedimentation did not affect the system
      because of the relatively small size of the colloidal particles and the charges
      present at their surfaces.

PMID- 20695612
TI  - Aggregative growth in the size-controlled growth of monodispersed gold
      nanoparticles.
AB  - This article describes the findings of an investigation of the aggregative growth
      mechanism for the formation of gold nanoparticles in aqueous solutions under
      ambient conditions with high monodispersity (2% RSD) over a wide range of
      particle sizes (10-100 nm). The utilization of the gold nanoparticles synthesized
      by this simple, reproducible growth mechanism has recently been demonstrated for
      establishing the size correlation for the surface plasmon resonance optical and
      surface-enhanced Raman scattering spectroscopic properties. The particle size,
      morphology, and optical properties of the nanoparticles produced at different
      stages of the growth processes were determined as a function of control
      parameters such as the reaction time and seed/precursor concentrations. The
      results have allowed us to establish a quantitative correlation between the
      growth size and the seed/precursor concentrations for the precise control of
      nanoparticle sizes. The kinetic measurements have demonstrated a polycrystalline
      character for the grown particles, a bimodal size distribution in the early stage
      of growth, sigmoidal kinetic behavior for the growth, and a correlation of the
      nucleation parameters with the particle size and distribution. These findings
      provided important indicators for the operation of an aggregative growth
      mechanism in the particle size growth and have important implications in
      understanding interparticle aggregation and coalescence in nanoparticle formation
      and growth under similar conditions.

PMID- 20695613
TI  - Organogels from functionalized T-shaped pi-conjugated bisphenazines.
AB  - This paper reports the electronic and organogelation properties of novel T-shaped
      bisphenazines functionalized with alkyl side groups and small peripheral cyano
      (CN) or aldehyde (CHO) substituents. UV-vis spectroscopy and cyclic voltammetry
      show the effect of the position, type, and number of the peripheral substituents
      on the electronic properties of the entire system. Interesting organogelation
      properties including a thixotropic behavior were observed from these T-shaped
      bisphenazines. We describe important findings from an in-depth characterization
      on the fibers formed by organogelation: (i) The position of the peripheral
      substituents influences the fiber morphology by modulating the intermolecular CN
      (or CHO) interaction and the pi-pi stacking. (ii) Compounds with CHO groups form
      islands of fiber aggregates, which is not the case for compounds with CN groups.
      (iii) Decyl-substituted compounds show higher gelation temperatures (i.e.,
      produce stronger gels) than hexadecyl-substituted ones. (iv) The thixotropic
      behavior originates from an extensive three-dimensional entanglement of very
      thin, flexible fibers.

PMID- 20695614
TI  - Reactive wet stamping for patterning of polyelectrolyte multilayers.
AB  - Patterning of soft films, especially their bulk and not only their surface
      properties, presents a challenge. Several lithographic techniques do exist, but
      many of them are complex or limited in their ability to change properties. A few
      methods of patterning polyelectrolyte multilayers (PEM) have been reported,
      including microcontact printing and selectively growing layers on patterned self
      assembled monolayers, but these all come with certain limitations. We present
      here the use of a modified microcontact printing method, reactive wet stamping (r
      WETs), using a hydrogel stamp soaked in aqueous solutions to create patterns in
      PEMs. With this technique we are able to locally cause swelling and porosity
      changes in the PEM films and use our method to qualitatively study the evolution
      of the porous film morphology. This technique has the potential to locally
      control chemical functionality, film thickness, and mechanical properties,
      leading to a new ability to control film architectures both at the film surface
      and within the bulk of the film.

PMID- 20695615
TI  - Ordered multimodal porous carbon as highly efficient counter electrodes in dye
      sensitized and quantum-dot solar cells.
AB  - Ordered multimodal porous carbon (OMPC) was explored as a counter electrode in
      ruthenium complex dye-sensitized solar cells (DSSCs) and CdSe quantum-dot solar
      cells (QDSCs). The unique structural characteristics such as large surface area
      and well-developed three-dimensional (3-D) interconnected ordered macropore
      framework with open mesopores embedded in the macropore walls make the OMPC
      electrodes have high catalytic activities and fast mass transfer kinetics toward
      both triiodide/iodide and polysulfide electrolytes. The efficiency (ca. 8.67%) of
      the OMPC based DSSC is close to that (ca. 9.34%) of the Pt based one. Most
      importantly, the QDSC employing OMPC material presents a high efficiency of up to
      4.36%, which is significantly higher than those of Pt- and activated carbon based
      solar cells, ca. 2.29% and 3.30%, respectively.

PMID- 20695616
TI  - Synthesis of monodisperse [Oct4N(+)][Au25(SR)18(-)] nanoparticles, with some
      mechanistic observations.
AB  - A single phase (THF) synthesis of monodisperse [Oct(4)N(+)][Au(25)(SR)(18)(-)]
      nanoparticles is described that yields insights into pathways by which it is
      formed from initially produced larger nanoparticles. Including the Oct(4)N(+)Br(
      ) salt in a reported single phase synthetic procedure enables production of
      reduced nanoparticles having a fully occupied HOMO molecular energy level
      (Au(25)(SR)(18)(-), as opposed to a partially oxidized state, Au(25)(SR)(18)(0)).
      The revised synthesis accommodates several (but not all) different thiolate
      ligands. The importance of acidity, bromide, and dioxygen on Au(25) formation was
      also assessed. The presence of excess acid in the reaction mixture steers the
      reaction toward making Au(25)(SR)(18); while bromide does not seem to affect
      Au(25) formation, but it may play a role in maintaining the -1 oxidation state.
      Conducting the nanoparticle synthesis and "aging" period in the absence of
      dioxygen (under Ar) does not produce small nanoparticles, providing insights into
      the pathway of reaction product "aging" in the synthesis solvent, THF. The
      "aging" process favors the Au(25)(-) moiety as an end point and possibly involves
      degradation of larger nanoparticles by hydroperoxides formed from THF and oxygen.

PMID- 20695617
TI  - Bioinspired blend membranes based on adenine and guanine functional poly(glycidyl
      methacrylate).
AB  - We have investigated adenine and guanine functional PGMAAdenine and PGMAGuanine
      as proton-conducting bioinspired membranes. Poly(glycidyl methacrylate) (PGMA)
      was prepared by free-radical polymerization and then modified with adenine and
      guanine molecules via ring opening of the epoxide ring. The complexed structure
      of the polymers was confirmed by FT-IR spectroscopy and (13)C CP-MAS NMR and
      elemental analysis studies. The blends of adenine and guanine functional polymers
      with phosphoric acid (H(3)PO(4)) and poly(vinyl phosphonic acid) (PVPA) were
      prepared in several stoichiometric ratios. The thermal and proton-conducting
      properties of these membranes were investigated in the anhydrous state.
      Phosphoric acid-doped polymers had lower T(g) values and higher proton
      conductivities than PVPA blends of adenine and guanine functional PGMA.
      (PGMAAdenine)-(H(3)PO(4))(2) had a maximum water-free proton conductivity of
      approximately 4 mS/cm at 150 degrees C.

PMID- 20695618
TI  - When does silica exchange occur between vinyl polymer-silica nanocomposite
      particles and sterically stabilized latexes?
AB  - The redistribution of silica nanoparticles between "core-shell" polymer-silica
      nanocomposites and sterically stabilized latexes is investigated using a
      combination of electron microscopy, disk centrifuge photosedimentometry (DCP),
      and X-ray photoelectron spectroscopy (XPS). Facile exchange of silica
      nanoparticles occurs on addition of sterically-stabilized polystyrene (or poly(2
      vinylpyridine)) latex to polystyrene-silica (or poly(2-vinylpyridine)-silica)
      nanocomposite particles previously prepared by heteroflocculation. In contrast,
      no silica exchange occurs after such a latex "challenge" if similar
      polymer/silica nanocomposite particles are prepared via in situ polymerization.
      Silica redistribution can be confirmed by post mortem electron microscopy
      studies, which are facilitated if the original nanocomposite and latex particles
      differ sufficiently in their mean diameters. Ideally, XPS requires a unique
      elemental marker for the nanocomposite particle cores, which become progressively
      more exposed if silica exchange occurs. DCP is a particularly convenient in situ
      technique for assessing whether or not silica exchange has occurred. If no silica
      exchange occurs, there is little or no change in the nanocomposite and latex size
      distributions. On the other hand, silica redistribution always results in a
      larger mean particle diameter for the (partially) silica-coated latex particles
      relative to the original bare latex. In addition, incipient flocculation is
      typically observed after silica exchange. Like electron microscopy, DCP studies
      are aided if there is a significant difference in particle diameter between the
      original polymer-silica nanocomposite particles and the added latex. Moreover,
      silica redistribution can be prevented for heteroflocculated polymer-silica
      nanocomposite particles under certain conditions. For example, although silica
      exchange is observed at pH 10 when adding sterically-stabilized polystyrene (or
      poly(2-vinylpyridine)) latex to heteroflocculated poly(2-vinylpyridine)-silica
      particles, it does not occur at pH 5. Presumably, this is due to greater
      electrostatic attraction between the cationic P2VP cores and the anionic silica
      nanoparticles at this lower pH.

PMID- 20695619
TI  - Vesicle formation and microphase behavior of amphiphilic ABC triblock copolymers
      in selective solvents: a Monte Carlo study.
AB  - Using Monte Carlo simulation, we studied the vesicle formation and microphase
      behavior of ABC triblock copolymers in selective solvent for A and C blocks.
      Simulation results show that the hydrophilicity of Blocks A and C determines not
      only the vesicle formation but also the microphase behavior. If Blocks A and C
      are of equal length, then Block A (with lower hydrophilicity) is likely to
      aggregate on the inner surface, whereas Block C (with higher hydrophilicity)
      tends to move to the outer surface, forming the ABC (from inside to outside)
      three-layer vesicle. Simulation results reveal that if the hydrophilicity
      difference between the two blocks is sufficiently low, then the ABC three layers
      are formed after the membrane closes (i.e., after the formation of vesicle
      profile). Otherwise, the ABC three layers are formed before the membrane closes.
      Furthermore, the effect of chain length and incompatibility between the two
      amphiphilic blocks (i.e., A and C) is studied and discussed in this article. The
      shorter block A is much more likely to aggregate on the inner surface, and the
      incompatibility between A and C must be sufficiently strong to ensure that the
      ABC copolymer forms an ABC (from inside to outside) three-layer vesicle.

PMID- 20695620
TI  - Facile one-step template-free synthesis of uniform hollow microstructures of
      cryptomelane-type manganese oxide K-OMS-2.
AB  - Hollow microstructures of cryptomelane-type manganese oxide were produced in a
      template-free one-step process based on the fine-tuning of the oxidation rate of
      manganese species during the synthesis. The tuning of the reaction rate brought
      about by a mixture of the oxidants oxone and potassium nitrate becomes apparent
      from the gradual physical changes taking place in the reaction medium at early
      times of the synthesis. The successful synthesis of the hollow uniform structures
      could be performed in the ranges 120-160 degrees C and 8.2-10.7 for temperature
      and mass ratio oxone/potassium nitrate, respectively. Independent of the
      conditions of the synthesis, all of the complex microstructures showed the same
      pattern for the array of very long nanofibers in which some of these elongated
      around the surface confining the cavity and the other fibers grew normal to the
      surface created by the previous arrangement. A mechanism based on the
      heterogeneous nucleation of the cryptomelane phase on the surface of an amorphous
      precursor and the growth of the nanoscale fibers by processes such as dissolution
      crystallization and lateral attachment of primary nanocrystalline fibers is
      proposed to explain the formation of the hollow structures.

PMID- 20695621
TI  - Redox-active concanavalin A: synthesis, characterization, and recognition-driven
      assembly of interfacial architectures for bioelectronic applications.
AB  - The convergence of chemistry, biology, and materials science has paved the way to
      the emergence of hybrid nanobuilding blocks that incorporate the highly selective
      recognition properties of biomolecules, with the tailorable functional
      capabilities of inorganic molecules. In this work, we describe for the first time
      the decoration of concanavalin A (Con A), a protein with the ability to recognize
      sugars and form glycoconjugates, with Os(II) redox-active complexes. This
      strategy enabled the construction of electroactive biosupramolecular materials
      whose redox potentials could be easily modulated through the facile molecular
      modification of the electroactive inorganic complexes. Small-angle X-ray
      scattering (SAXS), steady-state fluorescence, surface plasmon resonance (SPR)
      spectroscopy, matrix-assisted laser desorption/ionization-time-of-flight mass
      spectrometry (MALDI-TOF-MS), and differential-pulsed (DPV) and cyclic voltammetry
      (CV) were used to characterize the structural and functional features of the
      synthesized biohybrid building blocks as well as their respective supramolecular
      assemblies built up on gold electrodes. By harnessing the electroactive and
      carbohydrate-recognition properties of these tailor-made biohybrid building
      blocks, we were able to integrate glucose oxidase (GOx) onto gold electrodes via
      sugar-lectin interactions. The redox activity of the Os-modified Con A interlayer
      allowed the electronic connection between the multilayered GOx assemblies and the
      metal electrode as evidenced by the well-defined bioelectrocatalytic response
      exhibited by the biomolecular assemblies in the presence of the glucose in
      solution. We consider that this approach based on the spontaneous formation of
      redox-active biosupramolecular assemblies driven by recognition processes can be
      of practical relevance for the facile design of biosensors, as well as for the
      construction of new multifunctional bioelectrochemical systems.

PMID- 20695622
TI  - Electrochemical grafting of poly(3,4-ethylenedioxythiophene) into a titanium
      dioxide nanotube host network.
AB  - This study focuses on electrodeposition for infiltrating in situ a conducting
      polymer such as poly(3,4-ethylenedioxythiophene) (PEDOT) into a host titanium
      dioxide (TiO(2)) nanotube array (NTA) framework. The TiO(2) NTA was
      electrosynthesized on titanium foil in turn by anodization in a fluoride
      containing medium. The PEDOT layer was electrografted into the TiO(2) NTA
      framework using a two-step potentiostatic growth protocol in acetonitrile
      containing supporting electrolyte. The nanoscopic features of oligomer/polymer
      infiltration and deposition in the NTA interstitial voids were monitored by field
      emission scanning electron microscopy. Systematic changes in the nanotube inner
      diameter and the wall thickness afforded insights into the evolution of the
      TiO(2)NTA/PEDOT hybrid assembly. This assembly was subsequently characterized by
      UV-visible diffuse reflectance, cyclic voltammetry, and photoelectrochemical
      measurements. These data serve as a prelude to further use of these hybrids in
      heterojunction solar cells.

PMID- 20695623
TI  - Prototype of a porous ZnO SPV-based sensor for PCB detection at room temperature
      under visible light illumination.
AB  - To detect polychlorinated biphenyls (PCBs), a prototype of a porous ZnO sensor
      based on the surface photovoltage (SPV) mechanism working under visible light
      illumination at room temperature has been presented. The SPV of the porous ZnO
      sensor can be remarkably reduced under visible light illumination after PCB
      adsorption, and the reduction of amplitude is proportional to the population of
      adsorbed PCB molecules. We propose that the reduction of SPV response is due to
      trapping of the electrons in the surface states by the adsorbed PCBs. The lower
      detection limits of this new prototype sensor reach at least 2.2 micromol/L for
      PCB29 and 1.1 micromol/L for PCB101, respectively. So, it demonstrates great
      potential for practical application in trace detection of PCBs.

PMID- 20695624
TI  - Understanding pattern collapse in photolithography process due to capillary
      forces.
AB  - Photolithography is the most widely used mass nanoproduction process. Technology
      requirements demand smaller nanodevices. However, smaller features risk collapse
      during the drying of rinse liquid because of capillary forces. In the present
      study, progress is made on two fronts: (i) The importance of surface tension
      force (STF) on three-phase line on the pattern collapse is investigated. The STF
      was ignored in previous pattern collapse studies. It is found that inclusion of
      STF increases the pattern deformation. The calculated deformation error from
      neglecting STF increases by increasing contact angle, pattern height to width
      ratio, and trough to width ratio. The deformation error decreases with an
      increase in elasticity module of pattern. (ii) A more accurate representation for
      the interface curvature (and related Laplace pressure), that is, using Surface
      Evolver (SE) simulation rather than cylindrical interface model (CIM), is
      presented. Curvature values of two-line parallel and box-shaped patterns are
      derived from SE and compared with the curvature values from CIM. It was found
      that CIM for the case of two-line parallel overestimates the curvature value and
      for the case of box-shaped underestimates it. SE simulations also showed that the
      error of calculating curvature values using CIM for both shapes is only a
      function of LAR (ratio of pattern length to trough width). For LAR values less
      than 20, the curvature values from CIM are not accurate for calculating pattern
      deformation.

PMID- 20695625
TI  - Elliptical silicon arrays with anisotropic optical and wetting properties.
AB  - We demonstrate a facile etching method to fabricate silicon elliptical pillar
      arrays (Si-EPAs) with unique anisotropic optical and wetting characters using
      polystyrene elliptical hemisphere arrays (EHAs) as mask. The EHAs were fabricated
      via a modified micromolding method. By varying the experimental conditions in the
      fabrication process, the morphology of the resulting microstructures can be
      controlled exactly. Because of the anisotropic morphology of the elliptical
      pillar, the Si-EPA shows unique anisotropic properties, such as anisotropic
      surface reflection and anisotropic wetting property. Additionally, through
      oblique evaporation deposition of Au and selective chemical modification to turn
      the elliptical pillars into "Janus" elliptical pillars, the "Janus" Si-EPA shows
      more peculiar anisotropic properties owing to the further increased asymmetry. We
      believe that the Si-EPAs will have potential applications in anisotropic optical
      and electronic devices.

PMID- 20695626
TI  - Functionalized Ga2O3 nanowires as active material in room temperature capacitance
      based gas sensors.
AB  - We report the first evidence for functionalization of Ga(2)O(3) nanowires (NWs),
      which have been incorporated as the active material in room temperature
      capacitance gas-sensing devices. An adsorbed layer of pyruvic acid (PA) was
      successfully formed on Ga(2)O(3) NWs by simple room temperature vapor transport,
      which was confirmed by Fourier transform infrared spectroscopy. The effect of the
      adsorbed PA on the surface properties was demonstrated by the change in the
      response of the NW gas-sensing devices. Results indicate that the adsorption of
      PA reduced the sensitivity of the Ga(2)O(3) NW device to common hydrocarbons such
      as nitromethane and acetone while improving the response to triethylamine by an
      order of magnitude. Taking into account the simplicity of this functionalization
      together with the ease of producing these capacitance-based gas-sensing devices,
      this approach represents a viable technique for sensor development.

PMID- 20695627
TI  - Structural determinants for the stereoselective hydrolysis of chiral substrates
      by phosphotriesterase.
AB  - Wild-type phosphotriesterase (PTE) preferentially hydrolyzes the R(P) enantiomers
      of the nerve agents sarin (GB) and cyclosarin (GF) and their chromophoric
      analogues. The active site of PTE can be subdivided into three binding pockets
      that have been denoted as the small, large, and leaving group pockets based on
      high-resolution crystal structures. The sizes and shapes of these pockets dictate
      the substrate specificity and stereoselectivity for catalysis. Mutants of PTE
      that exhibit substantial changes in substrate specificity and the ability to
      differentiate between chiral substrates have been prepared. For example, the G60A
      mutant is stereoselective for the hydrolysis of the R(P) enantiomer of the
      chromophoric analogues of sarin and cyclosarin, whereas the H254G/H257W/L303T
      (GWT) mutant reverses the stereoselectivity for the enantiomers of these two
      compounds. Molecular dynamics simulations and high-resolution X-ray structures
      identified the correlations between structural changes in the active site and the
      experimentally determined kinetic parameters for substrate hydrolysis. New high
      resolution structures were determined for the H257Y/L303T (YT), I106G/F132G/H257Y
      (GGY), and H254Q/H257F (QF) mutants of PTE. Molecular dynamics calculations were
      conducted using the S(P) and R(P) enantiomers of the analogues for sarin and
      cyclosarin for the wild-type PTE and the G60A, YT, GGY, QF, and GWT mutants. The
      experimental stereoselectivity correlated nicely with the difference in the
      computed angle of attack for the nucleophilic hydroxide relative to the phenolic
      leaving group of the substrate.

PMID- 20695628
TI  - Development of a cysteine-catalyzed enantioselective Rauhut-Currier reaction.
AB  - Herein, we report a full account of the development of an enantioselective Rauhut
      Currier process that affords products in high yields and enantioselectivities
      using a cysteine-based catalyst. While traditional Morita-Baylis-Hillman
      catalysts were found to be essentially ineffective, various derivatives of
      protected cysteine were found to exhibit extraordinary reactivity and
      enantiotopic control. Extensive screening of reaction conditions led us to
      discover the enhanced effects of water as an additive and the chelating power of
      potassium in achieving higher enantiomer ratios. Mechanistic experiments also
      provided insight on the potential mechanism of the reaction in addition to
      possible transition states that provide the absolute stereochemistry formed in
      the observed products. Also included is a brief survey of the reaction scope
      involving different ring sizes as well as functionalized substrates.

PMID- 20695629
TI  - Excited-state triple-proton transfer in 7-azaindole(H(2)O)(2) and reaction path
      studied by electronic spectroscopy in the gas phase and quantum chemical
      calculations.
AB  - We have investigated the excited-state multiple-proton/hydrogen atom transfer
      reactions in the 7-azaindole water clusters, [7AI](H(2)O)(n) (n = 2,3), in the
      gas phase by combining electronic spectroscopy and quantum chemical calculations.
      The fluorescence excitation (FE) spectrum of 7AI(H(2)O)(2) has been observed by
      monitoring visible emission. In contrast, no vibronic bands are detected in the
      FE spectrum of 7AI(H(2)O)(3) when the visible emission is monitored. The
      dispersed fluorescence spectra of 7AI(H(2)O)(n) (n = 2,3) have been measured. The
      excitation of +180 cm(-1) band from the electronic origin of 7AI(H(2)O)(2)
      enhances the visible emission as compared with the 0-0 excitation. The +180 cm(
      1) band is assgined to an intermolecular mode (sigma(1)) of the cyclic hydrogen
      bonded ring structure. The calculated S(1)-S(0) absorption spectrum for the
      cyclic hydrogen-bonded structure is in agreement with the FE spectrum around the
      0-0 region. The excitation of sigma(1) significantly promotes the reaction and
      generates the tautomeric form of 7AI(H(2)O)(2). These experimental results on
      7AI(H(2)O)(n) (n = 2,3) are very similar to those on 7AI(CH(3)OH)(n) (n = 2,3)
      and 7AI(C(2)H(5)OH)(n) (n = 2,3). We conclude that the excited-state triple
      proton/hydrogen atom transfer (ESTPT/HT) occurs in 7AI(H(2)O)(2). Cuts of the
      potential energy surfaces along the proton/hydrogen atom transfer coordinates of
      7AI(H(2)O)(n) (n = 2,3) and 7AI(CH(3)OH)(n) (n = 2,3) are comparatively
      calculated by quantum chemistry calculations (RI-CC2/cc-pVDZ and TD-DFT(B3LYP)/cc
      pVDZ) to explore the mechanism of the ESTPT/HT reaction. The calculated results
      suggest that concerted proton transfers occur in 7AI(H(2)O)(2) as well as in
      7AI(CH(3)OH)(2), whereas the potential barrier for the excited-state quadruple
      proton transfer in 7AI(H(2)O)(3) and 7AI(CH(3)OH)(3) is higher than those for
      ESTPT. The theoretical results are consistent with the observation of ESTPT/HT in
      7AI(H(2)O)(2).

PMID- 20695630
TI  - B(80) and other medium-sized boron clusters: core-shell structures, not hollow
      cages.
AB  - Unbiased search on the potential energy surface of medium-sized boron clusters,
      with B(80), B(74), and B(68) as representatives, was carried out using simulated
      annealing incorporated with first-principles molecular dynamics. These boron
      clusters thermodynamically prefer the B(12)-centered core-shell structures, which
      resemble the fragment of bulk boron solids. Though these core-shell clusters lack
      a descriptive symmetry and may not be the true global minima, the core-shell
      B(80) is about 25 meV/atom lower in energy than the widely assumed highly stable
      "magic" B(80) fullerene. The electronic states and photoelectron spectra of these
      clusters are closely correlated to the structural motif, which may be helpful for
      detecting the cluster configurations in experiments.

PMID- 20695632
TI  - Direct patterning of covalent organic monolayers on silicon using nanoimprint
      lithography.
AB  - Two fabrication schemes are reported for the direct patterning of organic
      monolayers on oxide-free silicon, combining top-down nanoimprint lithography and
      bottom-up monolayer formation. The first approach was designed to form monolayer
      patterns on the imprinted areas, while the second approach was designed for
      monolayer formation outside of the imprinted features. By both approaches,
      covalently bonded Si-C monolayer patterns with feature sizes ranging from 100 nm
      to 100 microm were created via a hydrosilylation procedure using diluted
      reagents. Both unfunctionalized and omega-functionalized alkenes were patterned
      successfully.

PMID- 20695631
TI  - A systematically coarse-grained solvent-free model for quantitative phospholipid
      bilayer simulations.
AB  - We present an implicit solvent coarse-grained (CG) model for quantitative
      simulations of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayers.
      The absence of explicit solvent enables membrane simulations on large length and
      time scales at moderate computational expense. Despite improved computational
      efficiency, the model preserves chemical specificity and quantitative accuracy.
      The bonded and nonbonded interactions together with the effective cohesion
      mimicking the hydrophobic effect were systematically tuned by matching structural
      and mechanical properties from experiments and all-atom bilayer simulations, such
      as saturated area per lipid, radial distribution functions, density and pressure
      profiles across the bilayer, P(2) order, etc. The CG lipid model is shown to self
      assemble into a bilayer starting from a random dispersion. Its line tension and
      elastic properties, such as bending and stretching modulus, are
      semiquantitatively consistent with experiments. The effects of (i) reduced
      molecular friction and (ii) more efficient integration combine to an overall
      speed-up of 3-4 orders of magnitude compared to all-atom bilayer simulations. Our
      CG lipid model is especially useful for studies of large-scale phenomena in
      membranes that nevertheless require a fair description of chemical specificity,
      e.g., membrane patches interacting with movable and transformable membrane
      proteins and peptides.

PMID- 20695633
TI  - Radical chemistry in the thermal decomposition of anisole and deuterated
      anisoles: an investigation of aromatic growth.
AB  - The pyrolyses of anisole (C(6)H(5)OCH(3)), d(3)-anisole (C(6)H(5)OCD(3)), and
      d(8)-anisole (C(6)D(5)OCD(3)) have been studied using a hyperthermal tubular
      reactor and photoionization reflectron time-of-flight mass spectrometer. Gas
      exiting the reactor is subject to an immediate supersonic expansion after a
      residence time of approximately 65 mus. This allows the detection of highly
      reactive radical intermediates. Our results confirm that the first steps in the
      thermal decomposition of anisole are the loss of a methyl group to form phenoxy
      radical, followed by ejection of a CO to form cyclopentadienyl radical (c
      C(5)H(5)); C(6)H(5)OCH(3) --> C(6)H(5)O + CH(3); C(6)H(5)O --> c-C(5)H(5) + CO.
      At high temperatures (T(wall) = 1200 degrees C - 1300 degrees C) the c-C(5)H(5)
      decomposes to propargyl radical (CH(2)CCH) and acetylene; c-C(5)H(5) --> CH(2)CCH
      + C(2)H(2). The formation of benzene and naphthalene is demonstrated with 1 + 1
      resonance-enhanced multiphoton ionization. Propargyl radical recombination is a
      significant benzene formation channel. However, we show the majority of benzene
      is formed by a ring expansion reaction of methylcyclopentadiene (C(5)H(5)CH(3))
      resulting from methyl radical addition to cyclopentadienyl radical; CH(3) + c
      C(5)H(5) --> C(5)H(5)CH(3) --> C(6)H(6) + 2H. The naphthalene is generated from
      cyclopentadienyl radical recombination; 2c-C(5)H(5) --> C(5)H(5)-C(5)H(5) -->
      C(10)H(8) + 2H. The respective intermediate amu 79 and 129 species associated
      with these reactions are detected, confirming the stepwise nature of the
      decompositions. These reactions are verified by pyrolysis studies of
      cyclopentadiene (C(5)H(6)) and C(5)H(5)CH(3) obtained from rapid thermal
      dissociation of the respective dimer compounds, as well as pyrolysis studies of
      propargyl bromide (BrCH(2)CCH).

PMID- 20695634
TI  - Subporphyrinoid systems: a theoretical study of the effects of the diheteroatom
      substitution in pyrrole subunits and of the nature of the bridging meso linkages.
AB  - A theoretical study of the geometry, the electronic structure, the electronic
      absorption spectra, and (1)H and (13)C NMR spectra of the [14]subporphine(1.1.1)
      hydroxyboron(III) complex, free-base subporphyrin, and its dioxygen and dithio
      pyrrole substituted derivatives using CH, N, and P as bridging meso linkages was
      performed at the B3LYP/6-311+G(2d,p)//B3LYP/6-31G(d) theory level. The
      geometrical structure of these systems is mainly determined by the internal area
      delimited by the meso atoms and the alpha-carbon atoms of the pyrrolic rings, and
      by the number and nature of the atoms located on this area. All the hydroxyboron
      subporphyrins and dioxo and dithio subporphyrins with CH meso connectors display
      a conical shaped geometry. The presence of strong repulsions between the atoms on
      the central zone of the remaining systems provokes a correlative tilting of one
      of the three rings with loss of the conical shape with important consequences on
      spectroscopic properties. A particularly interesting case is the
      dioxosubporphyrin with P connectors in which the large area of the central zone
      determined by these connectors allows for an almost planar geometry that endows
      it with special features. The molecules presenting a tilted ring display weak
      absorption bands. Generally, the intensity of the bands moderately increases when
      the geometry is cone shaped. The dioxo heterosubporphyrins with CH (conical
      shape) and P (almost planar) connectors present strong absorption bands. (1)H and
      (13)C chemical shifts clearly reflect the effect of geometry distortion provoked
      by the repulsion among the atoms of the central area of the system indicating a
      deep perturbation of the pi system of the molecules.

PMID- 20695635
TI  - Computational chemical studies on thermochemistry and ring strains in cyclic
      [n]metaphenyleneacetylenes, butadiyne-bridged [4n]metacyclophynes, and butadiyne
      bridged [4n]paracyclophynes.
AB  - The thermochemical properties and ring strains in cyclic
      [n]metaphenyleneacetylenes ([n]CMPAs), butadiyne-bridged [4(n)]metacyclophynes (B
      B[4(n)]MCs), and butadiyne-bridged [4(n)]paracyclophynes (B-B[4(n)]PCs) were
      studied using a homodesmotic reaction scheme coupled with density functional
      theory (B3LYP/6-31G*, mPW1PW91/6-31G*, and M06-2X/6-31+G**//B3LYP/6-31G*). Strain
      energies of [n]CMPAs and B-B[4(n)]MCs decrease first from very high values for
      small rings to become zero when n becomes 6, then increase with n, and finally
      decrease as n becomes larger than 8. In the case of B-B[4(n)]PCs, strain energies
      decrease with increasing n. Heats of formation of [n]CMPAs, B-B[4(n)]MCs, and B
      B[4(n)]PCs increase steadily with increasing numbers of phenylacetylene and 1
      (buta-1,3-diynyl)benzene to reach a near-constant value per unit monomer as n
      increases. The geometries and (vibrational and nuclear magnetic resonance)
      spectroscopic properties of [n]CMPAs, B-B[4(n)]MCs, and B-B[4(n)]PCs were also
      studied. Geometrical parameters, Raman frequencies, and (1)H NMR chemical shifts
      of [3]CMPA and [4]CMPA are found to be in good agreement with compounds for which
      there are experimentally available values at the B3LYP/6-31G* level of theory. In
      addition, electronic structure calculations were carried out for [n]CMPAs, B
      B[4(n)]MCs, and B-B[4(n)]PCs. Ring diameters were also calculated for B
      B[4(n)]PCs.

PMID- 20695636
TI  - Zwitterionic chitosan derivatives for pH-sensitive stealth coating.
AB  - Zwitterionic chitosan, a chitosan derivative with a unique pH-dependent charge
      profile, was employed to create a stealth coating on the cationic surface of drug
      carriers. Zwitterionic chitosans were synthesized by amidation of chitosan with
      succinic anhydride. The succinic anhydride-conjugated chitosan had an isoelectric
      point, which could be easily tuned from pH 4.9 to 7.1 and showed opposite charges
      below and above the isoelectric point. The succinic anhydride-conjugated chitosan
      was able to inhibit the protein adsorption to the cationic surface at
      physiological pH, compatible with blood components and well tolerated upon
      intraperitoneal injection. The succinic anhydride-conjugated chitosan has the
      potential to serve as a coating material to prevent protein adsorption to
      cationic surfaces, which can be removed in a pH-responsive manner.

PMID- 20695637
TI  - Polymeric drugs based on random copolymers with antimitotic activity.
AB  - Polymeric drugs based on random copolymers with antimitotic activity were
      obtained by free radical copolymerization of oleyl 2-acetamido-2-deoxy-alpha-d
      glucopyranoside methacrylate (OAGMA) and 2-ethyl-(2-pyrrolidone) methacrylate
      (EPM) at low and high conversion and analyzed in terms of microstructure,
      physicochemical, and biological properties. Reactivity ratios of monomers were
      found to be r(OAGMA) = 1.34 and r(EPM) = 0.98, indicating the obtaining of
      statistical copolymers with random sequence distribution of the comonomeric units
      in the macromolecular chains. The glass transition temperature of the copolymers
      presents a negative deviation from the predicted values according to the Fox
      equation, suggesting a higher flexibility of the alternating diad. Copolymeric
      systems with OAGMA contents between 10-50 mol % presented thermosensitive
      behavior in a heating process showing cloud point temperatures (CPT) in the range
      45-28  degrees C with increasing OAGMA content and hysteresis in one heating-and
      cooling cycle. In vitro glycolipid release studies revealed the stability of the
      ester group in culture medium. The polymeric drugs with 30 and 50 mol % OAGMA
      presented antimitotic activity on a human glioblastoma line, but they were less
      toxic on normal human fibroblast cultures.

PMID- 20695638
TI  - Fast screening and secure confirmation of milk powder adulteration with
      maltodextrin via electrospray ionization-mass spectrometry [ESI(+)-MS] and
      selective enzymatic hydrolysis.
AB  - Direct-infusion electrospray ionization-mass spectrometry [ESI(+)-MS] of several
      milk powder samples, confiscated by the Brazilian Federal Police, showed ions
      accounting for sodiated and potassiated molecules of disaccharides (m/z 365 and
      381) as well as trisaccharides (m/z 527 and 543), whereas monosaccharide ions
      were not detected. The trisaccharide ions were not detected in samples of genuine
      milk powder, raising the suspicion that their presence indicates adulteration by
      the addition of maltodextrin. In control samples, maltose and maltotriose were
      hydrolyzed by alpha-glucosidase and not beta-galactosidase, whereas lactose was
      resistant to alpha-glucosidase but was hydrolyzed with beta-galactosidase.
      Samples suspected of being adulterated behaved in the same fashion, confirming
      the presence of maltose and maltotriose or maltodextrin. Direct-infusion ESI-MS
      is shown therefore to provide rapid screening of milk powder for adulteration
      with maltodextrin, whereas its combination with selective enzymatic hydrolysis
      provides highly reliable confirmation for unambiguous results.

PMID- 20695639
TI  - Attempted confirmation of the provenance of Corsican PDO honey using FT-IR
      spectroscopy and multivariate data analysis.
AB  - This study investigated the potential of Fourier-transform infrared (FT-IR)
      spectroscopy and chemometric techniques to produce a mathematical model that
      would confirm or refute the provenance of honeys claiming to be Corsican.
      Authentic honey samples from two harvest seasons (2004/2005 and 2005/2006) were
      collected from Ireland (n=2), Italy (n=30), Austria (n=40), Germany (n=36),
      mainland France (n=46), and Corsica (n=219). Prior to scanning, samples were
      diluted with distilled water to a standard solids content (70 degrees Brix).
      Spectra (2500-12500 nm) were recorded at room temperature using a FT-IR
      spectrometer equipped with a germanium attenuated total reflectance (ATR)
      accessory. Standard normal variate (SNV) and first- and second-derivative data
      pretreatments were applied to the recorded spectra, which were processed using
      factorial discriminant analysis (FDA) and partial least-squares (PLS) regression
      analysis. Overall correct classification figures of 82% (FDA) and 87% (PLS) were
      obtained for a separate validation set comprising samples from both harvests.

PMID- 20695641
TI  - Photochemical addition of C60 with siliranes: synthesis and characterization of
      carbosilylated and hydrosilylated C60 derivatives.
AB  - Photochemical reactions of C(60) with siliranes (1a-d) afford adducts of four
      types (2a-5b) as carbosilylated and hydrosilylated C(60) derivatives.
      Characterization of these adducts was conducted using MS, UV, NMR spectroscopy,
      and single-crystal X-ray analyses. In particular, the first example of the
      crystal structure of a closed 1,2-adduct at the 5,6-ring junction of the C(60)
      cage is provided by single-crystal X-ray analysis of 3b. Electrochemical analyses
      also revealed unique redox properties of the products 2b-5b, which depend on the
      regiochemistry of the functionality, in addition to the substituents on the C(60)
      cage. Theoretical calculations offer bases for the experimentally observed redox
      properties and relative stabilities of the silylated products.

PMID- 20695642
TI  - Slow reductive elimination from arylpalladium parent amido complexes.
AB  - We report reductive eliminations of primary arylamines from a series of
      bisphosphine-ligated arylpalladium(II) parent amido complexes that counter
      several established trends. In contrast to arylamido and alkylamido complexes of
      the aromatic bisphosphines DPPF and BINAP, parent amido complexes of these
      ligands do not form or undergo reductive elimination of monoarylamines. However,
      arylpalladium parent amido complexes ligated by the alkylbisphosphine CyPF-t-Bu
      do form in good yield and undergo reductive elimination. Despite the basicity of
      the parent amido ligand and the typically faster reductive elimination from
      complexes containing more basic amido ligands, the CyPF-t-Bu-ligated
      arylpalladium parent amido complexes undergo reductive elimination much more
      slowly than the analogous complexes containing arylamido or alkylamido ligands.
      Moreover, the parent amido complexes form more rapidly and are more stable
      thermodynamically in a series of exchange processes than the arylamido complexes.
      Computational studies support the overriding influence of steric effects on the
      stability and reactivity of the parent amido complex. The slow rate of reductive
      elimination causes the arylpalladium amido complex to be the resting state of the
      coupling of aryl halides with ammonia catalyzed by CyPF-t-Bu-ligated palladium,
      and this resting state contrasts the Pd(0) or arylpalladium(II) resting states of
      reactions of aryl halides with amines catalyzed by most palladium complexes.

PMID- 20695643
TI  - On the relationship between lateralized brain function and orienting asymmetries.
AB  - Hemispheric specializations for language perception constitute one of the classic
      topic in cognitive neuroscience. Evidence has accumulated to suggest that
      lateralized acoustic processing is not restricted to humans but is also found in
      numerous animal species. One of the methods used to track such lateralization is
      the orienting-asymmetry paradigm, a simple, noninvasive means to study
      lateralization that has been applied to a range of different species ranging from
      harpy eagles to humans. Here we summarize and compare the results of studies
      employing the orienting-asymmetry paradigm, showing that these studies yield
      largely inconsistent results. We critically discuss the methodology's implicit
      assumptions and conclude that the empirical inconsistencies produced by the
      orienting-asymmetry paradigm, and the lack of sufficient evidence supporting the
      paradigm's underlying assumptions, warrant serious caution when interpreting
      results obtained by the method. Nontrivial interpretations of orienting-asymmetry
      results will require a much better understanding of how lateralized brain
      functions interact with overt behaviors.

PMID- 20695644
TI  - Arrest of adult hippocampal neurogenesis in mice impairs single- but not multiple
      trial contextual fear conditioning.
AB  - The role of adult hippocampal neurogenesis in contextual fear conditioning (CFC)
      is debated. Several studies demonstrated that blocking adult hippocampal
      neurogenesis in rodents impairs CFC, while several other studies failed to
      observe an impairment. We sought to determine whether different CFC methods vary
      in their sensitivity to the arrest of adult neurogenesis. Adult neurogenesis was
      arrested in mice using low-dose, targeted x-irradiation, and the effects of
      irradiation were assayed in conditioning procedures that varied in the use of a
      discrete conditioned stimulus, the number of trials administered, and the final
      level of conditioning produced. We demonstrate that irradiation impairs CFC in
      mice when a single-trial CFC procedure is used but not when multiple-trial
      procedures are used, regardless of the final level of contextual fear produced.
      In addition, we show that the irradiation-induced deficit in single-trial CFC can
      be rescued by providing preexposure to the conditioning context. These results
      indicate that adult hippocampal neurogenesis is required for CFC in mice only
      when brief training is provided.

PMID- 20695645
TI  - Differential responses to serotonin receptor ligands in an impulsive-aggressive
      phenotype.
AB  - Offensive aggression in golden hamsters is inhibited by 5-hydroxytryptamine (5
      HT)1A receptors and facilitated by 5-HT3 receptor activation. As such, we sought
      to determine whether these receptors function similarly between animals
      expressing an impulsive-aggressive phenotype, as compared to normal animals.
      Animals were screened for aggressive and impulsive choice behaviors and
      categorized into Low-Aggression (L-Agg) and High-Aggression (H-Agg) groups, and
      then tested for behavior under effective doses of 5-HT1A receptor agonist 8
      hydroxy-N, N-dipropyl-2-aminotetralin (DPAT; 0.1 mg/kg and 0.3 mg/kg) or 5-HT3
      receptor antagonist tropisetron (0.3 mg/kg) treatment. Low-dose DPAT treatment
      inhibited both behaviors in H-Agg animals, however yielding more modest effects
      in L-Agg animals; while high-dose DPAT effects were confounded by side effects on
      locomotion. Tropisetron, on the other hand, had differential effects between
      groups, as aggression and impulsive choice were both inhibited in H-Agg animals,
      while enhanced in L-Agg individuals. In addition, while the effects of the 5-HT1A
      receptor were limited, the broad effects of 5-HT3 receptor included repetitive
      and impulsive elements of behavior, pointing to the importance of the receptor's
      role in the modulation of these particular aspects within the phenotype.

PMID- 20695646
TI  - Self-administered cocaine causes long-lasting increases in impulsive choice in a
      delay discounting task.
AB  - Cocaine use is associated with high levels of impulsive choice (preference for
      immediate over delayed rewards), but it is not clear whether cocaine use causes
      elevated impulsive choice, or whether elevated impulsive choice is solely a
      predisposing factor for cocaine use. This study examined the effects of prior
      cocaine self-administration on rats performing a delay discounting task commonly
      used to measure impulsive choice. Male Long-Evans rats were implanted with
      intravenous catheters, and following recovery, were trained to self-administer 30
      mg/kg/day cocaine HCl (approx. 0.5 mg/kg/infusion) for 14 consecutive days (a
      control group received yoked intravenous saline infusions). Following three weeks
      of withdrawal, all rats were food-restricted and began training on the delay
      discounting task in standard operant chambers. On each trial, rats were given a
      choice between two levers. A press on one lever delivered a small food reward
      immediately, and a press on the other delivered a large food reward after a
      variable delay period. Rats that self-administered cocaine displayed greater
      impulsive choice (enhanced preference for the small immediate over the large
      delayed reward, as reflected by shorter indifference points) compared to
      controls, but were no different from controls on a "probabilistic discounting"
      task in which they chose between small certain and large uncertain rewards. These
      data suggest that self-administered cocaine can cause lasting elevations in
      impulsive choice, and that the high levels of impulsive choice observed in human
      cocaine users may be due in part to long-term effects of cocaine on brain
      function.

PMID- 20695647
TI  - Conditioning with masked stimuli affects the timecourse of skin conductance
      responses.
AB  - In Pavlovian fear conditioning, an aversive unconditional stimulus (UCS) is
      repeatedly paired with a neutral conditional stimulus (CS). As a consequence, the
      subject begins to show conditional responses (CRs) to the CS that indicate
      expectation and fear. There are currently two general models competing to explain
      the role of subjective awareness in fear conditioning. Proponents of the single
      process model assert that a single propositional learning process mediates CR
      expression and UCS expectancy. Proponents of a dual-process model assert that
      these behavioral responses are expressions of two independent learning processes.
      We used backward masking to block perception of our visual CSs and measured the
      effect of this training on subsequent unmasked performance. In two separate
      experiments we show a dissociation between CR expression and UCS expectancy
      following differential delay conditioning with masked CSs. In Experiment I, we
      show that masked training facilitates CR expression when the same CSs are
      presented during a subsequent unmasked reacquisition task. In Experiment II we
      show that masked training retards learning when the CS+ is presented as part of a
      compound CS during a subsequent unmasked blocking task. Our results suggest that
      multiple memory systems operate in a parallel, independent manner to encode
      emotional memories.

PMID- 20695648
TI  - Olfactory bulb habituation to odor stimuli.
AB  - Habituation is a simple form of memory, yet its neurobiological mechanisms are
      only beginning to be understood in mammals. In the olfactory system, the neural
      correlates of habituation at a fast experimental timescale involving very short
      intertrial intervals (tens of seconds) have been shown to depend on synaptic
      adaptation in olfactory cortex. In contrast, behavioral habituation to odorants
      on a longer timescale with intertrial intervals of several minutes depends on
      processes in the olfactory bulb, as demonstrated by pharmacological studies. We
      here show that behavioral habituation to odorants on this longer timescale has a
      neuronal activity correlate in the olfactory bulb. Spiking responses of mitral
      cells in the rat olfactory bulb adapt to, and recover from, repeated odorant
      stimulation with 5-min intertrial intervals with a time course similar to that of
      behavioral habituation. Moreover, both the behavioral and neuronal effects of
      odor habituation require functioning N-methyl-d-aspartic acid receptors in the
      olfactory bulb.

PMID- 20695649
TI  - Operant learning requires NMDA-receptor activation in the anterior cingulate
      cortex and dorsomedial striatum, but not in the orbitofrontal cortex.
AB  - Previous research has shown that corticostriatal N-methyl-D-aspartate receptor
      (NMDAR) activation is necessary for operant learning. NMDAR activation induces
      plasticity-related intracellular signaling processes leading to gene expression,
      which are hypothesized to be important steps in codifying the content of
      learning. Operant learning induces immediate early gene (IEG) expression in key
      corticostriatal structures, namely the dorsomedial striatum (DMS), the
      orbitofrontal (OFC), and anterior cingulate cortices (ACC). Both the ACC and OFC
      send glutamatergic projections to the DMS, which is a crucial site for operant
      behavior. However, the role of NMDAR activation in these corticostriatal regions
      in operant learning is unknown. To test this hypothesis, the NMDA antagonist AP-5
      (1 microg/0.5 microl) or saline was bilaterally microinjected into the ACC, OFC,
      and DMS of food-deprived rats just prior to operant learning sessions. NMDAR
      antagonism in the ACC and DMS impaired the acquisition of lever pressing for
      sucrose pellets but had no effect on lever pressing once learned. NMDAR blockade
      in OFC did not significantly impair operant learning, suggesting that NMDAR
      activation in operant learning is site-specific. These data extend our
      understanding of the role of NMDA receptors in operant learning and behavior
      throughout an extended corticostriatal network.

PMID- 20695650
TI  - Opioid regulation of Pavlovian overshadowing in fear conditioning.
AB  - In Pavlovian overshadowing, a stimulus that predicts a biologically important
      event reduces conditioning to another, equally predictive stimulus. We tested the
      effects of an opioid antagonist and dopamine agonist on the ability of a salient
      white noise to overshadow a less salient light. Rats were conditioned to fear a
      light or a noise-light compound using a mild footshock. Compound-conditioned rats
      trained under the saline vehicle revealed significant overshadowing of the light
      by the noise. This overshadowing effect was significantly attenuated in rats
      trained under the opioid antagonist naltrexone, consistent with an opioid
      mediated negative feedback model of conditioning. In line with predictions made
      by negative feedback-type models, we failed to obtain overshadowing with few
      trials, suggesting that the processes underlying conditioning during initial
      trials do not contribute to the opioid-dependent Pavlovian overshadowing obtained
      in our preparation. Lastly, we compared the involvement of dopamine-mediated and
      opioid-mediated processes in overshadowing by conditioning rats under the partial
      dopamine D1 receptor agonist SKF 38393 or the opioid antagonist naltrexone. Both
      naltrexone and SKF 38393 were found to attenuate overshadowing; however, the
      behavioral profiles produced by each pharmacological manipulation were distinct.
      Collectively, these studies demonstrate an important role for both opioid- and
      dopamine-mediated processes in multiple-trial overshadowing.

PMID- 20695651
TI  - Effects of multiple daily nicotine administrations on pre- and post-nicotine
      circadian activity episodes in rats.
AB  - Administration of a single daily dose of nicotine has been shown to entrain
      circadian activity episodes both preceding and following the administration time
      that persist for several days after drug administration ceases. The present study
      tested the effects of multiple daily nicotine administrations on circadian
      activity episodes in adult female rats kept under constant light and rate-limited
      food access. Eight rats received 7 separate 7-day nicotine injection series, each
      followed by a 3-day test phase without injections. Subcutaneous nicotine was
      administered once a day during the 1st and 7th series, twice daily during the 2nd
      and 6th series, three times daily during the 3rd and 5th series, and four times
      daily during the 4th series. To control the cumulative daily dose throughout the
      study, 1.0 mg/kg nicotine was evenly divided among the injections within a single
      day. Pre- and post-administration effects of nicotine declined across the day,
      and significant entrainment of both pre- and post-nicotine episodes occurred for
      only one daily injection in each series. Additionally, post-nicotine episodes
      showed a different dose-response curve than the pre-nicotine episodes: post
      nicotine wheel turns increased as the dose decreased, whereas pre-nicotine wheel
      turns remained relatively constant as the dose changed. These results provide
      evidence that nicotine-induced circadian entrainment to a single administration
      time does occur when the drug is administered multiple times a day, and pre- and
      post-nicotine circadian episodes are mediated at least partially by separate
      mechanisms.

PMID- 20695652
TI  - Human navigation that requires calculating heading vectors recruits parietal
      cortex in a virtual and visually sparse water maze task in fMRI.
AB  - Spatial navigation in the real-world is a complex task that involves many
      functions, such as landmark identification, orientation, and the calculation of
      heading vectors. This study uses a 2 x 2 experimental design with fMRI to isolate
      mnemonic and navigational processes that accompany the calculation of heading
      vectors. The conditions are based on a working memory version of the Morris water
      maze task and navigation takes place in a visually austere virtual environment.
      In an allocentric condition, subjects navigate around a circular arena where
      there is one small red square on the wall. Each trial begins with an encoding
      phase in which subjects locate and navigate to a visible coin. Then, in a test
      phase, after being randomly repositioned, they retrieve the coin when it is
      invisible. In a control task, there are eight distinct cues around the arena that
      provide direct cue-place information. Results show significant interaction
      effects in bilateral posterior parietal cortex, which is compatible with evidence
      that parietal cortex helps translating between allocentric coordinates and
      egocentric directions. There was also greater activation for the allocentric task
      in right posterior hippocampus and left retrosplenial cortex, which could be
      related to self-localization and orientation. The findings are also compatible
      with the recent proposal by Kubie and Fenton (2009) that navigation primarily
      depends on heading vectors between salient places.

PMID- 20695653
TI  - Characterization of neurotoxic effects of NMDA and the novel neuroprotection by
      phytopolyphenols in mice.
AB  - Excitotoxicity plays a major role in various neurological disorders. In this
      study, we explored the behavioral and neurotoxic effects of intraventricular NMDA
      administration in mice. After NMDA injection, acute seizures were followed by
      impairments in locomotor activity, motor performance on a rotarod, and climbing
      ability. Mice killed 1 day after NMDA administration showed increased
      synaptosomal reactive oxygen species ROS production and calcium concentration and
      decreased mitochondrial membrane potential, mitochondrial reductase activities,
      and neuronal membrane Na+, K+ -ATPase and mg2+ -ATPase activities. One and 3 days
      after excitotoxic injury, Golgi stains showed that dendritic length and spine
      density were significantly decreased in neurons of the hippocampal dentate gyrus.
      Some mice received honokiol, tea polyphenol plus memantine, and honokiol plus
      memantine prior to NMDA treatment; the occurrence of generalized seizures was
      attenuated, seizure scores were reduced, latency to generalized seizures was
      prolonged, and motor impairments were lessened. Moreover, all of the
      neurochemical changes of the synaptosomes were also ameliorated. In conclusion,
      the behavioral and neurotoxic effects of intracerebroventricular injection of
      NMDA were ameliorated by treatment with honokiol alone or combined treatment with
      either tea polyphenol plus memantine or honokiol plus memantine, but only partly
      by either tea polyphenol or memantine alone. The therapeutic potential of these
      neuroprotective regimens in treating excitotoxicity-related diseases merits for
      further investigation.

PMID- 20695654
TI  - Serotonin impairs copulation and attenuates ejaculation-induced glutamate
      activity in the medial preoptic area.
AB  - The medial preoptic area (MPOA) is critical for male sexual behavior. Glutamate
      is released in the MPOA of male rats during copulation, and increasing glutamate
      levels by reverse dialysis of glutamate uptake inhibitors facilitates mating.
      Conversely, increased release of serotonin (5-HT) inhibits sexual behavior. In
      both rats and men, selective serotonin reuptake inhibitors (SSRIs) impair
      erection, ejaculation, and libido. Here we reverse-dialyzed 5-HT through
      concentric microdialysis probes in the MPOA of male rats; concurrently we
      collected 2-min samples for analysis of glutamate and measured sexual behavior.
      Sexual activity, and especially ejaculation, increased levels of glutamate in the
      MPOA. However, reverse dialysis of 5-HT into the MPOA impaired ejaculatory
      ability and attenuated glutamate release. Implications of these results for
      impairment of sexual behavior that results from administration of SSRIs are
      discussed.

PMID- 20695656
TI  - Species differences in executive function correlate with hippocampus volume and
      neocortex ratio across nonhuman primates.
AB  - A persistent debate in behavioral research is whether brain size or architecture
      relates to cognitive performance. A growing body of evidence has demonstrated
      correlations between brain size and ecological and behavioral tasks. These
      studies are premised on a causal link between brain size and cognitive function,
      although this association has little empirical backing. We show, for a set of 46
      species from 17 primate genera, that competence on a series of eight executive
      function cognitive tasks both correlate across tasks and with brain size and
      architecture across species. Our model selection approach showed that, although
      several measures of brain component volumes are significantly associated with
      performance, hippocampus size is the best predictor of overall performance. The
      best performing model also includes total brain size and relative neocortex size.
      Additionally, absolute measures are much more predictive of performance than
      relative measures of brain and brain component size. These results are consistent
      with the hippocampus' role in learning, and the executive brain (neocortex) being
      important for problem solving and consolidation. Our findings challenge and
      extend those of previous analyses by clarifying the relationship between overall
      brain size and specific regional volumes. They also suggest that commonly used
      indices of encephalization, such as residuals of brain volume regressed on body
      size, may confound rather than clarify matters.

PMID- 20695657
TI  - Visual contrast modulates maturation of camouflage body patterning in cuttlefish
      (Sepia pharaonis).
AB  - Camouflage is the primary defense behavior in cephalopods. It is known that
      cuttlefish immediately after hatching are capable of showing various body
      patterns for concealing themselves, however recent studies suggest that
      maturation of camouflage body patterns is faster for cuttlefish (Sepia
      officinalis) reared in enriched environments than those reared in impoverished
      environments. Since camouflage patterning in cephalopods is predominately
      visually driven, this study specifically investigates effects of the rearing
      background contrast on the maturation of body patterns in cuttlefish (Sepia
      pharaonis). Newly hatched animals were separated into two cohorts, one reared in
      a uniform-gray background (low-contrast, or L group) and the other raised in a
      black/white checkerboard background (high-contrast, or H group). At Weeks 2, 4,
      6, 8, 10, and 12, cuttlefish were placed individually either on uniform or
      checkerboard substrates to examine their body patterns. Animals from both L and H
      groups appear to show moderate disruptive patterns on the checkerboard and less
      disruptive on the uniform background at Week 2. Throughout development, however,
      cuttlefish from the H group showed stronger disruptive patterns than that of the
      L group on the checkerboard background at Weeks 10 and 12. In interesting
      findings, cuttlefish from both L and H groups showed similar strength but
      different disruptive components on the uniform background in later postembryonic
      stages. These results suggest that the maturation of camouflage body patterns in
      S. pharaonis is at least in part affected by visual contrast of their rearing
      backgrounds, although environmental complexity or social interaction is also
      likely to be involved in this process. This also implies that early visual
      experience could exert its effect on the seemingly preprogrammed behaviors such
      as camouflage body patterning in cephalopods.

PMID- 20695658
TI  - Capuchins (Cebus apella) can solve a means-end problem.
AB  - Three capuchin monkeys (Cebus apella) were tested on a 2-choice discrimination
      task designed to examine their knowledge of support, modeled after Hauser,
      Kralik, and Botto-Mahan's (1999) experiments with tamarins. This task involved a
      choice between 2 pieces of cloth, including 1 with a food reward placed on its
      surface, and a second cloth with the food reward next to its surface. After
      reliably solving the basic problem, the capuchins were tested with various
      alternations of the original food reward and cloth. The capuchins were able to
      solve the initial task quickly, and generalize their knowledge to additional
      functional and nonfunctional variations of the problem. In comparison to the
      tamarins previously tested on this problem (Hauser et al., 1999), the capuchins
      were able to reach criterion faster during the training and food size conditions
      and showed a greater ability to inhibit reaching toward larger food rewards that
      were unavailable.

PMID- 20695659
TI  - Chimpanzee (Pan troglodytes) consolation: third-party identity as a window on
      possible function.
AB  - Consolation, that is, postconflict affiliative contact by a bystander toward a
      recipient of aggression, has acquired an important role in the debate about
      empathy in great apes because it has been proposed that the reassuring behavior
      aimed at distressed parties reflects empathetic arousal. However, the function of
      this behavior is not fully understood. The present study tests specific
      predictions about the identity of bystanders on the basis of a database of 1102
      agonistic interactions and their corresponding postconflict periods in two
      outdoor-housed groups of captive chimpanzees (Pan troglodytes). We found that
      recipients of aggression were more likely to be contacted by their own "friends"
      than by "friends" of the aggressor and that frequent targets of aggression were
      not more likely to offer consolation than were nontargets of aggression. These
      findings support the stress reduction hypothesis rather than two proposed
      alternatives, that is, the opponent relationship repair hypothesis and the self
      protection hypothesis. Our results provide further support for relationship
      quality as a fundamental underlying factor explaining variation in the occurrence
      of consolation.

PMID- 20695655
TI  - A comparative view of face perception.
AB  - Face perception serves as the basis for much of human social exchange. Diverse
      information can be extracted about an individual from a single glance at their
      face, including their identity, emotional state, and direction of attention.
      Neuropsychological and functional magnetic resonance imaging (fMRI) experiments
      reveal a complex network of specialized areas in the human brain supporting these
      face-reading skills. Here we consider the evolutionary roots of human face
      perception by exploring the manner in which different animal species view and
      respond to faces. We focus on behavioral experiments collected from both primates
      and nonprimates, assessing the types of information that animals are able to
      extract from the faces of their conspecifics, human experimenters, and natural
      predators. These experiments reveal that faces are an important category of
      visual stimuli for animals in all major vertebrate taxa, possibly reflecting the
      early emergence of neural specialization for faces in vertebrate evolution. At
      the same time, some aspects of facial perception are only evident in primates and
      a few other social mammals, and may therefore have evolved to suit the needs of
      complex social communication. Because the human brain likely utilizes both
      primitive and recently evolved neural specializations for the processing of
      faces, comparative studies may hold the key to understanding how these parallel
      circuits emerged during human evolution.

PMID- 20695661
TI  - Maternal separation alters social odor preference development in infant mice (Mus
      musculus).
AB  - This study examined whether daily periods of maternal separation during the first
      two weeks of life would decrease attraction to familiar nest odors in CD-1 mice
      10 and 14 days old. We also investigated whether placing a group of mice (Mus
      musculus) in nest shavings during the 180-min separation period would mitigate
      possible separation-induced deficits. The maternal separation procedure has been
      widely used as a rodent model for the effects of inconsistent or inadequate early
      caretaking on human development. From postnatal day (PND) 1 to 14, litters were
      separated from the dam, but not littermates for either 15 or 180 min, or were
      facility-reared controls. Control, facility-reared mice preferred home-cage nest
      to clean familiar shaving odors on PND 10, but not PND 14. In contrast, home-cage
      nest odors attracted maternally separated mice on both test days. Our results
      suggest that maternal separation maintains the olfactory tether to the nest in a
      period when the attraction normally begins to weaken.

PMID- 20695660
TI  - Attention to emotional scenes including whole-body expressions in chimpanzees
      (Pan troglodytes).
AB  - Real-life situations provide rich sets of cues that viewers evaluate in terms of
      their emotional significance. In this study, chimpanzees (Pan troglodytes) viewed
      a movie depicting naturalistic scenes involving the whole-body expressions of
      conspecifics to examine how nonhuman primates perceived the combination of these
      cues and how each cue contributed to the overall perception. Viewing time was
      measured while the chimpanzees watched movie clips without sound. Among scenes
      depicting neutrality, general excitement, agonism, and playfulness, chimpanzees
      looked longest at those depicting agonism. This bias toward agonistic scenes may
      indicate an attentional sensitivity toward threat/fear-related negative
      situations among chimpanzees. The effect disappeared when the images were
      scrambled, ruling out the possible effect of pixel-level properties on the
      results. In addition, the follow-up analyses revealed that the effect was
      independent of the presentation order and of the number of individuals in each
      clip. The manipulation of playback speeds had little effect on the looking times.
      The elimination of facial cues slightly influenced the looking times but did not
      change the strong bias toward agonistic scenes. This robustness of the main
      effect against image manipulations may indicate that the chimpanzees attended
      directly to the contextual information implied by the cues rather than to the
      cues per se (e.g., facial expressions, speed of movements).

PMID- 20695662
TI  - Rats (Rattus norvegicus) in a water maze learn both an egocentric trajectory and
      landmarks.
AB  - In two experiments we investigated the extent to which rats (Rattus norvegicus)
      use an egocentric trajectory and landmarks to locate a goal. In Experiment 1 we
      trained groups to locate the hidden platform in a water maze with either 1 of 3
      or 3 of 3 predictive landmarks, and with either a random or fixed egocentric
      trajectory. A choice test revealed that regardless of the landmark configuration,
      rats relied on a directional, egocentric trajectory, when it was available, to
      locate the platform. In Experiment 2 we found that adding four predictive
      landmarks following training with a constant egocentric trajectory did not alter
      rats' initial attention to the trajectory. We conclude that the presence of
      nonpredictive landmarks in a predictive array did not affect the use of
      landmarks. With a blocking design, rats used initially an egocentric path, then
      landmarks. These results add to the notion that animals use available spatial
      cues sequentially.

PMID- 20695664
TI  - Do bantams (Gallus gallus domesticus) experience amodal completion? An analysis
      of visual search performance.
AB  - Whereas many mammals (some primates and mice) experience amodal completion,
      previous data split for avian species. However, experimental procedures have been
      quite different among the species, and thus a direct comparison of various avian
      species in the same experimental situation is needed. We tested whether bantams
      (Gallus gallus domesticus) would complete partly occluded figures using a visual
      search task on the touch monitor, which was successfully used in our previous
      study with pigeons. First, we trained 3 participants to search for a notched red
      diamond (a target) among complete diamonds (distracters). Next, white squares
      accompanied each figure with a small gap of a fixed size. In test, the location
      of the accompanying white squares sometimes changed. In some trials, the white
      squares exactly covered, or "occluded," the notched portion of the target. Humans
      are known to have great difficulty in finding such targets due to "automatic"
      completion of the notched part. However, bantams met no such difficulty at all.
      This result and the demonstration by Forkman (1998) of hens' amodal completion of
      figures placed on a perspective background, suggest that the perspective cue may
      have an important role in amodal completion in this species.

PMID- 20695663
TI  - Behavioral measures of auditory streaming in ferrets (Mustela putorius).
AB  - An important aspect of the analysis of auditory "scenes" relates to the
      perceptual organization of sound sequences into auditory "streams." In this
      study, we adapted two auditory perception tasks, used in recent human
      psychophysical studies, to obtain behavioral measures of auditory streaming in
      ferrets (Mustela putorius). One task involved the detection of shifts in the
      frequency of tones within an alternating tone sequence. The other task involved
      the detection of a stream of regularly repeating target tones embedded within a
      randomly varying multitone background. In both tasks, performance was measured as
      a function of various stimulus parameters, which previous psychophysical studies
      in humans have shown to influence auditory streaming. Ferret performance in the
      two tasks was found to vary as a function of these parameters in a way that is
      qualitatively consistent with the human data. These results suggest that auditory
      streaming occurs in ferrets, and that the two tasks described here may provide a
      valuable tool in future behavioral and neurophysiological studies of the
      phenomenon.

PMID- 20695665
TI  - Behavioral science, engineering, and poetry revisited.
AB  - Forty years ago, Lehrman (1971) identified 2 orientations to the study of animal
      behavior. The natural history orientation conducted field and lab research
      designed to reveal how animals cope with the circumstances of their natural
      environment. Such research reveals the diversity among different types of animals
      and differences between the world of animals and the world of humans (i.e.,
      "poetry"). In contrast, the anthropocentric orientation studies animals either to
      generate animal-derived general laws applicable to humans or to provide
      experimental information that, for ethical and practical reasons, cannot be
      acquired from human research. The primary motivation for the anthropocentric
      orientation is to provide workable models for investigating specifically human
      problems (i.e., "engineering"). Evidence is presented from the study of bird song
      that demonstrates the contribution that the "poetic" approach can make to
      anthropocentric ("engineering") concerns.

PMID- 20695666
TI  - Integrated primary care meets health reform.

PMID- 20695667
TI  - Primary care-mental health integration in healthcare in the Department of
      Veterans Affairs.
AB  - The U.S. Department of Veterans Affairs (VA) has been undergoing tremendous
      transformation in the past 15 years with regard to the delivery of health care.
      This special issue describes one aspect of this transformation of the largest
      health system in the U.S.; the system-wide efforts to integrate mental health
      treatment into the primary care setting in VA. This primary care-mental health
      integration (PC-MHI) is being accomplished through the central VA system support
      and implementation of three primary models developed in the field: the White
      River Colocated models, the Behavioral Health Laboratory, and TIDES (Translating
      Initiatives in Depression into Effective Solutions). The papers in this special
      issue describe the development of these models, local and regional efforts to
      prepare medical centers to adapt and implement PC-MHI, and the impact of the
      integration on mental health care in these settings. These efforts could
      represent a national model of PC-MHI implementation for health care systems
      throughout the U.S.

PMID- 20695668
TI  - Integrating mental health into primary care within the Veterans Health
      Administration.
AB  - The Veterans Health Administration (VHA) has been undertaking a major
      transformational program of integrating collaborative mental health resources
      into primary care settings. Key components of the program include colocated
      collaborative care provided by mental health professionals; care management; and
      blended programs that combine elements of these two components, whose functions
      are highly complementary to each other. The program has grown since 2007 from an
      initiative implementing pilot programs at participating facilities, to a routine
      expectation of primary care within all VHA medical centers and large community
      based outpatient clinics. The national program office supports this VHA
      initiative in multiple ways, including technical assistance to sites, program and
      policy development, dissemination of informational tools to facilitate continuous
      quality improvement, education and training, and partnerships with other existing
      and emerging VHA programs such as postdeployment health clinics and the patient
      centered medical home.

PMID- 20695669
TI  - Using evidence-based quality improvement methods for translating depression
      collaborative care research into practice.
AB  - OBJECTIVE: Translating Initiatives in Depression into Effective Solution (TIDES)
      aimed to translate research-based collaborative care for depression into an
      approach for the Veterans Health Administration (VA). SITES: Three multistate
      administrative regions and seven of their medium-sized primary care practices.
      INTERVENTION: Researchers assisted regional leaders in adapting research-based
      depression care models using evidence-based quality improvement (EBQI) methods.
      EVALUATION: We evaluated model fidelity and impacts on patients. Trained nurse
      depression care managers collected data on patient adherence and outcomes.
      RESULTS: Among 72% (128) of the 178 patients followed in primary care with
      depression care manager assistance during the 3-year study period, mean PHQ-9
      scores dropped from 15.1 to 4.7 (p < .001). A total of 87% of patients achieved a
      PHQ-9 score lower than 10 (no major depression). 62% achieved a score lower than
      six (symptom resolution). Care managers referred 28% (50) TIDES patients to
      mental health specialty (MHS). In the MHS-referred group, mean PHQ-9 scores
      dropped from 16.4 to 9.0 (p < .001). A total of 58% of MHS-referred patients
      achieved a PHQ-9 score lower than 10, and 40%, a score less than 6. Over the 2
      years following the initial development phase reported here, national
      policymakers endorsed TIDES through national directives and financial support.
      CONCLUSIONS: TIDES developed an evidence-based depression collaborative care
      prototype for a large health care organization (VA) using EBQI methods. As
      expected, care managers referred sicker patients to mental health specialists;
      these patients also improved. Overall, TIDES achieved excellent overall patient
      outcomes, and the program is undergoing national spread.

PMID- 20695670
TI  - The White River model of colocated collaborative care: A platform for mental and
      behavioral health care in the medical home.
AB  - In the past two decades a great deal of research has demonstrated improved
      quality of care when mental health care is integrated into primary care. To date,
      most of the literature has addressed care management for specific mental
      illnesses. Such programs can be difficult to implement and sustain. We describe a
      program of "Colocated Collaborative Care," implemented in 2004 that has been
      sustained and grown over the 6 years since inception. The Primary Mental Health
      Care clinic at the White River Junction (Vermont) Veterans Affairs Medical Center
      offers a full spectrum of mental health care that allows 75% of referred patients
      to receive all of their care within the primary care clinic, thus conserving
      scarce specialty services for the most complex patients. The clinic is staffed by
      a therapist and a psychiatrist (or advanced practice nurse) and complemented by
      care management and health psychology. It makes use of technology to streamline
      assessment and track outcomes. The clinic provides a mix of care management,
      specialty expertise and chronic disease management. Originally developed in a
      capitated health care system, adherence to general principles that guided its
      development may be useful in any system of care.

PMID- 20695671
TI  - The Behavioral Health Laboratory: building a stronger foundation for the patient
      centered medical home.
AB  - The Veterans Health Affairs is in the process of implementing a new model for the
      delivery of primary care: The Patient-Centered Medical Home (PCMH). One critical
      challenge of any PCMH model will be the integration of basic mental health
      treatment into primary care. Such a mental health integration program must be
      flexible enough to incorporate new evidence-based treatments as patient
      demographics and health care needs evolve over time. This paper summarizes the
      Behavioral Health Laboratory (BHL) care management model, a program already in
      place in more than 20 Veterans Affairs facilities along with private sector
      insurance providers, as ideally suited to fill this role in the PCMH. The BHL
      uses a platform of standardized, software-aided mental health assessments and
      clinical care managers to deliver evidence-based treatments for depression,
      anxiety, and substance abuse in primary care settings. The authors review this
      comprehensive program of screening, assessment, treatment, and referral to
      specialty care when needed. The BHL program is consistent with the guiding
      principles of the Patient-Centered Medical Home: applying chronic illness disease
      management principles to provide more continuous, coordinated, and efficient
      primary care services to patients with diverse needs. Just as importantly, the
      authors review how this standardized platform for delivering integrated mental
      health services provides the flexibility to incorporate novel interventions for a
      changing population.

PMID- 20695672
TI  - The description and evaluation of the implementation of an integrated healthcare
      model.
AB  - Two studies were conducted to examine the practical implementation of an
      integrated health care model in five primary care clinics in the Upstate New York
      Veterans Affairs (VA) system. The aims of the studies were: (a) to describe the
      basic clinical elements of the integrated health care service offered by
      behavioral health providers (BHPs) in the primary care setting, and (b) to
      evaluate the perceptions of providers and patients regarding integrated health
      care practices in their primary care clinics. In Study 1, we reviewed 180
      electronic medical records of patients who met with a BHP in primary care. In
      Study 2, we used semistructured interviews and self-report questionnaires to
      collect information from 46 primary care providers, 12 BHPs, and 140 patients
      regarding their perceptions of integrated health care in their primary care
      clinics. Both studies illustrate a useful method for evaluating the practical
      implementation of integrated health care models.

PMID- 20695673
TI  - Using a multi-level approach to implement a primary care mental health (PCMH)
      program.
AB  - Successfully spreading innovation across large health care systems is a complex
      process requiring participation of stakeholders from a broad spectrum of
      professional backgrounds, skill sets, and organizational levels. We describe a
      process for engaging and activating stakeholders across individual, team,
      organization, and system levels to implement primary care-mental health
      integrated care programs in one regional Veterans Affairs health care network.
      Key stakeholders and researchers collaborated to propose and implement the
      program. Preliminary findings indicate that the program may reduce referrals to
      specialty mental health care.

PMID- 20695674
TI  - St. Louis Initiative for Integrated Care Excellence (SLI(2)CE): integrated
      collaborative care on a large scale model.
AB  - The primary care health setting is in crisis. Increasing demand for services,
      with dwindling numbers of providers, has resulted in decreased access and
      decreased satisfaction for both patients and providers. Moreover, the
      overwhelming majority of primary care visits are for behavioral and mental health
      concerns rather than issues of a purely medical etiology. Integrated
      collaborative models of health care delivery offer possible solutions to this
      crisis. The purpose of this article is to review the existing data available
      after 2 years of the St. Louis Initiative for Integrated Care Excellence; an
      example of integrated-collaborative care on a large scale model within a regional
      Veterans Affairs Health Care System. There is clear evidence that the SLI(2)CE
      initiative rather dramatically increased access to health care, and modified
      primary care practitioners' willingness to address mental health issues within
      the primary care setting. In addition, data suggests strong fidelity to a model
      of integrated-collaborative care which has been successful in the past.
      Integrated-collaborative care offers unique advantages to the traditional view
      and practice of medical care. Through careful implementation and practice,
      success is possible on a large scale model.

PMID- 20695684
TI  - Transfer of task-switching training in older age: the role of verbal processes.
AB  - This study investigated the influence of verbal self-instructions (VSI) on the
      transfer of task-switching training in older adults (56-78 years). We applied an
      internally cued switching paradigm in a pretest-training-posttest design.
      Training-related improvements were not modulated by VSI. Transfer (the pretest
      posttest reduction of switch costs) was most pronounced when participants applied
      the VSI at posttest after practicing the switching task without VSI. The results
      indicate that in contrast to transfer of executive control training, transfer of
      (verbal) strategy training seems to be limited and that VSI is most beneficial
      when the task-switching abilities are already well practiced.

PMID- 20695685
TI  - Bupropion sustained release treatment decreases craving for video games and cue
      induced brain activity in patients with Internet video game addiction.
AB  - Bupropion has been used in the treatment of patients with substance dependence
      based on its weak inhibition of dopamine and norepinephrine reuptake. We
      hypothesized that 6 weeks of bupropion sustained release (SR) treatment would
      decrease craving for Internet game play as well as video game cue-induced brain
      activity in patients with Internet video game addiction (IAG). Eleven subjects
      who met criteria for IAG, playing StarCraft (>30 hr/week), and eight healthy
      comparison subjects (HC) who had experience playing StarCraft (<3 days/week and
      <1 hr/day). At baseline and at the end of 6 weeks of bupropion SR treatment,
      brain activity in response to StarCraft cue presentation was assessed using 1.5
      Tesla functional MRI. In addition, symptoms of depression, craving for playing
      the game, and the severity of Internet addiction were evaluated by Beck
      Depression Inventory, self-report of craving on a 7-point visual analogue scale,
      and Young's Internet Addiction Scale, respectively. In response to game cues, IAG
      showed higher brain activation in left occipital lobe cuneus, left dorsolateral
      prefrontal cortex, and left parahippocampal gyrus than HC. After a 6 week period
      of bupropion SR, craving for Internet video game play, total game play time, and
      cue-induced brain activity in dorsolateral prefrontal cortex were decreased in
      the IAG. We suggest that bupropion SR may change craving and brain activity in
      ways that are similar to those observed in individuals with substance abuse or
      dependence.

PMID- 20695687
TI  - Acute effects of intranasal oxytocin on subjective and behavioral responses to
      social rejection.
AB  - The hormone and neuropeptide oxytocin is believed to buffer against social stress
      and reduce social-threat perception. We employed a widely used ostracism
      paradigm, Cyberball, to investigate whether oxytocin ameliorated the acute
      behavioral and affective consequences of social rejection. In a double-blind,
      randomized, between-subjects design, 74 healthy male and female participants were
      administered intranasal oxytocin or placebo and subsequently ostracized or
      included during this virtual ball-tossing game. Ostracized participants reported
      negative affective and attachment-related reactions, as well as a significant
      motivational change in increased desire to be involved in the game; these effects
      were not influenced by oxytocin. Intranasal oxytocin did, however, increase
      included participants' desire to play again with the same participants,
      suggesting oxytocin enhanced desire for future social engagement following
      inclusion. These findings are argued to provide evidence that the effects of
      oxytocin in promoting social approach behavior may be context specific and
      sensitive to positive social cues. The results suggest that in an explicitly
      aversive context, oxytocin does not buffer against the immediate impact of blunt
      social rejection.

PMID- 20695686
TI  - Effects of oral caffeine pretreatment on response to intravenous nicotine and
      cocaine.
AB  - Previous research suggests that under conditions of chronic daily caffeine
      administration, caffeine increases the effects of nicotine. Little is known about
      the effects of caffeine pretreatment on response to nicotine under infrequent
      caffeine administration conditions. The present study examined whether infrequent
      (not on consecutive days) acute oral caffeine administration alters subject
      rated, physiological, and monetary value effects of intravenous nicotine in
      regular users of caffeine, tobacco, and cocaine. To determine the specificity of
      effects of caffeine on response to nicotine, the effects of caffeine
      administration on response to intravenous cocaine (another short-acting
      stimulant) were also studied. Fourteen (1 woman) volunteers participated in this
      3-4 week, double-blind, inpatient study. Volunteers participated in 10
      experimental conditions in pseudo-randomized order, in which oral caffeine (250
      mg/70 kg) or placebo was administered 1 hr before an intravenous injection,
      consisting of nicotine (1 or 2 mg/70 kg), cocaine (15 or 30 mg/70 kg), or saline.
      Infrequent acute caffeine pretreatment attenuated the increase resulting from 2
      mg/70 kg nicotine administration on ratings of "rush," "good effects," "liking,"
      "high," and "drowsy/sleepy." Caffeine had no significant effect on physiological
      response to nicotine. Caffeine had no significant effect on subject-rated and
      physiological response to cocaine, with the exception that caffeine significantly
      augmented blood pressure response to cocaine. In contrast to the previous
      research using chronic caffeine maintenance, these data suggest that infrequent
      acute caffeine administration may attenuate nicotine effects.

PMID- 20695688
TI  - Development of a simulated drinking game procedure to study risky alcohol use.
AB  - The aim of the current study was to initiate and describe the development of a
      Simulated Drinking Game Procedure (SDGP), a safe, efficient, and alcohol-free
      laboratory protocol for studying drinking game behavior. Fifty-two undergraduates
      completed the SDGP in a laboratory session, where participants played singles
      and/or doubles games of Beer Pong. Water was substituted for alcohol in all of
      the games. The number of drinks consumed during matches and 20-min play periods
      were coded during each session, and software was used to estimate the peak blood
      alcohol concentration (BAC) a participant would achieve if he or she had consumed
      actual alcohol while participating in the SDGP. Results indicated that
      participation in Beer Pong can lead to rapid consumption of alcohol and an
      associated rise in BAC. Results also highlight additional risks for female
      participants associated with participation in drinking games. The SDGP is a
      research tool capable of increasing our understanding of drinking games.

PMID- 20695689
TI  - Perception of alcohol intoxication shows acute tolerance while executive
      functions remain impaired.
AB  - Several psychological constructs (e.g., subjective perception of intoxication,
      visuomotor speed) display acute tolerance to alcohol, that is, show improvement
      at declining blood alcohol concentrations (BACs) relative to equivalent rising
      BACs. However, methodological challenges emerge when attempting to make such
      comparisons across limbs of the BAC curve, which have proven a barrier to
      advancing research on acute tolerance. To date, no studies have made multiple
      comparisons across the entire BAC trajectory. This study employs experimental
      procedures that overcome some of these difficulties, offering a clearer picture
      of recovery of impairment for subjective perception of intoxication and cognitive
      performance and the relationship between them. Twenty participants were assessed
      at multiple time points over 2 days. Continuous subjective perception of
      intoxication ratings and cognitive data derived from a computerized measure were
      paired with a novel analytic paradigm, which allowed comparisons at identified
      BACs. Results showed acute tolerance for individuals' subjective perception of
      intoxication and for performance on cognitive tasks measuring visuomotor speed
      and learning efficiency (recovery from impairment). In contrast, performance on
      measures of executive function and short-term memory showed no significant
      difference between limbs at exact concentrations (no recovery from impairment).
      Therefore, despite participants feeling less intoxicated over time, many
      cognitive functions remained impaired. The implication for these findings in
      terms of drunken driving behavior are substantial, suggesting that people may be
      likely to drive once they subjectively perceive that they have recovered from the
      acute intoxicating effects of alcohol, despite the persistence of "higher order"
      cognitive impairments.

PMID- 20695690
TI  - Craving and physiological reactivity to trauma and alcohol cues in posttraumatic
      stress disorder and alcohol dependence.
AB  - The high comorbidity of posttraumatic stress disorder (PTSD) and alcohol
      dependence (AD) has been firmly established. Although laboratory studies have
      examined self-reported craving in response to trauma and alcohol cues, no studies
      have reported on alcohol-related physiological responding in response to trauma
      cues in PTSD-AD individuals. Using a cue reactivity paradigm, this study examined
      the impact of personalized trauma-image cues and in vivo alcohol cues on alcohol
      related responding (e.g., salivation, craving) in individuals with PTSD and AD (n
      = 40). Participants displayed reactivity to both trauma and alcohol cues when
      compared to neutral cues, including increased self-reported craving and distress,
      as well as greater salivation. These findings suggest that through repeated
      pairings of trauma memories and alcohol consumption, salivation may become
      classically conditioned to trauma cues. Moreover, the fact that the trauma
      alcohol cue combination elicited greater alcohol craving, salivary responding,
      distress, and arousal than either the trauma-neutral or neutral-alcohol cue
      combinations suggests that effects of the trauma and alcohol cues were additive
      in nature. Evidence that AD individuals with PTSD report increased alcohol
      craving and display greater salivation in response to trauma memories,
      supplements prior research indicating that PTSD-related negative emotion and
      trauma-related alcohol craving may play an important role in the maintenance of
      AD.

PMID- 20695691
TI  - Nicotine's enhancing effects on responding maintained by conditioned reinforcers
      are reduced by pretreatment with mecamylamine, but not hexamethonium, in rats.
AB  - Several studies have indicated that nicotine increases responding maintained by
      conditioned reinforcers. We assessed the effects of subcutaneous injections of
      0.3 mg/kg nicotine and two nicotinic antagonists on responding maintained by
      conditioned and primary reinforcers and responding during extinction in 8 Long
      Evans rats. Mecamylamine, a central and peripheral nicotinic antagonist, and
      hexamethonium, a peripheral nicotinic antagonist, were administered prior to a
      subset of the experimental sessions. Nicotine selectively increased responding
      maintained by conditioned reinforcers and mecamylamine, but not hexamethonium,
      attenuated this effect. These results suggest that nicotine's enhancing effect on
      responding maintained by conditioned reinforcers is mediated in the central
      nervous system.

PMID- 20695692
TI  - Repeated administration of pioglitazone attenuates development of hyperalgesia in
      a rat model of neuropathic pain.
AB  - Recent studies indicate the central neuroimmune and neuroinflammation activation
      play a critical role in the pathological states of pain. Pioglitazone, a potent
      synthetic agonists of PPARgamma, has shown to control neuroinflammation in many
      nervous system-related disorders. The present study was designed to explore the
      effects of pioglitazone in treating neuropathic pain and its possible neuroimmune
      mechanisms in the neuropathic pain using lumbar 5 (L5) spinal nerve transection
      rat model. L5 spinal nerve transection was done to produce hyperalgesia in rats.
      Pioglitazone (2.5, 5, and 10 mg/kg) was orally administered daily for 14 days,
      beginning from 1 hour before nerve transection. Mechanical hyperalgesia was
      measured using Von-Frey filament tests before and after the surgery. Rats were
      then sacrificed on day 14 postsurgery. The mRNA of inflammatory cytokines such as
      tumor necrosis factor (TNF-alpha), interleukin (IL-1beta) and nuclear factor
      kappa B (NF-kappaB) activity in brain were detected using reverse transcription
      polymerase chain reaction and electrophoretic mobility shift assay. We found that
      pioglitazone (5 and 10 mg/kg) can markedly attenuate mechanical hyperalgesia
      produced by nerve transection, most significantly on the 14th day. The elevated
      TNF-alpha, IL-1beta, and NF-kappaB in brain were accordingly reduced. Our data
      could conclude that pioglitazone has ameliorative potential in attenuating the
      painful state associated with L5 nerve transection, which may further be
      attributed to inhibiting cerebral proinflammatory cytokines production and NF
      kappaB activation in central nervous system.

PMID- 20695694
TI  - Psychometric evaluation of a Prescription Stimulant Expectancy Questionnaire.
AB  - Expectancies influence the initiation and maintenance of substance use. Given the
      increasing literature devoted to the rise of prescription stimulant misuse, an
      examination of expectancy effects associated with prescription stimulant use
      appears warranted. This study employed a revised version of the Prescription
      Stimulant Expectancy Questionnaire (PSEQ) and examined its psychometric
      properties in a nationwide sample of 547 participants. An exploratory factor
      analysis of the 46-item revised questionnaire (PSEQ-II) identified 4 factors:
      Cognitive Enhancement, Anxiety and Arousal, Social Enhancement, and Guilt and
      Dependence. The PSEQ-II successfully discriminated among user groups (i.e.,
      nonusers, recreational users, medical users, recreational/medical users).
      Recreational/medical users held the strongest positive expectancies and nonusers
      held the weakest; negative expectancies were held most strongly by nonusers and
      weakest by medical users. Use of the PSEQ-II and knowledge of prescription
      stimulant-related expectancies may assist in the prevention and treatment of
      prescription stimulant misuse.

PMID- 20695693
TI  - The short of it: abbreviating the temporal discounting procedure.
AB  - A typical temporal discounting procedure determines the present, subjective value
      (indifference point) of a delayed outcome at 5 to 8 different delays to that
      outcome. These indifference points are used to determine a single index of
      discounting called a discounting rate. One concern that remains in the collection
      of this data is the high number of trials or choices, resulting in participant
      fatigue or other factors that may affect the validity of the data. In this
      report, we propose an abbreviated alternative to the more comprehensive and time
      consuming discounting procedure. Specifically, we propose that fewer indifference
      points can be used to determine statistically equivalent discount rates with no
      loss in data sensitivity. We reanalyzed temporal discounting data obtained with 7
      indifference points, and estimated discount rates from all combinations of 2, 3,
      and 4 of the 7 indifference points. Results indicate that valid and sensitive
      discounting indices can be obtained with fewer indifference points, and the most
      appropriate sets of indifference points are highlighted. The proposed abbreviated
      procedure is likely to be particularly useful when time constraints or
      participant fatigue is a concern as well as in repeated-measures contexts.

PMID- 20695695
TI  - Face, body, and center of gravity mediate person detection in natural scenes.
AB  - Person detection is an important prerequisite of social interaction, but is not
      well understood. Following suggestions that people in the visual field can
      capture a viewer's attention, this study examines the role of the face and the
      body for person detection in natural scenes. We observed that viewers tend first
      to look at the center of a scene, and only then to fixate on a person. When a
      person's face was rendered invisible in scenes, bodies were detected as quickly
      as faces without bodies, indicating that both are equally useful for person
      detection. Detection was optimized when face and body could be seen, but
      observers preferentially fixated faces, reinforcing the notion of a prominent
      role for the face in social perception. These findings have implications for
      claims of attention capture by faces in that they demonstrate a mediating
      influence of body cues and general scanning principles in natural scenes.

PMID- 20695696
TI  - Picture detection in rapid serial visual presentation: features or identity?
AB  - A pictured object can be readily detected in a rapid serial visual presentation
      sequence when the target is specified by a superordinate category name such as
      animal or vehicle. Are category features the initial basis for detection, with
      identification of the specific object occurring in a second stage (Evans &
      Treisman, 2005), or is identification of the object the basis for detection? When
      2 targets in the same superordinate category are presented successively (lag 1),
      only the identification-first hypothesis predicts lag 1 sparing of the second
      target. The results of 2 experiments with novel pictures and a wide range of
      categories supported the identification-first hypothesis and a transient
      attention model of lag 1 sparing and the attentional blink (Wyble, Bowman, &
      Potter, 2009).

PMID- 20695697
TI  - Competing for consciousness: prolonged mask exposure reduces object substitution
      masking.
AB  - In object substitution masking (OSM) a sparse, temporally trailing 4-dot mask
      impairs target identification, even though it has different contours from, and
      does not spatially overlap with the target. Here, we demonstrate a previously
      unknown characteristic of OSM: Observers show reduced masking at prolonged (e.g.,
      640 ms) relative to intermediate mask durations (e.g., 240 ms). We propose that
      with prolonged exposure, the mask's visual representation is consolidated, which
      allows processing of the lingering target icon to be reinitiated, thereby
      improving performance. Our findings suggest that when the visual system is
      confronted with 2 temporally contiguous stimuli, although one may initially gain
      access to consciousness above the other, the "losing" stimulus is not
      irreversibly lost to awareness.

PMID- 20695698
TI  - Compatibility of motion facilitates visuomotor synchronization.
AB  - Prior research indicates that synchronized tapping performance is very poor with
      flashing visual stimuli compared with auditory stimuli. Three finger-tapping
      experiments compared flashing visual metronomes with visual metronomes containing
      a spatial component, either compatible, incompatible, or orthogonal to the
      tapping action. In Experiment 1, synchronization success rates increased
      dramatically for spatiotemporal sequences of both geometric and biological forms
      over flashing sequences. In Experiment 2, synchronization performance was best
      when target sequences and movements were directionally compatible (i.e.,
      simultaneously down), followed by orthogonal stimuli, and was poorest for
      incompatible moving stimuli and flashing stimuli. In Experiment 3,
      synchronization performance was best with auditory sequences, followed by
      compatible moving stimuli, and was worst for flashing and fading stimuli. Results
      indicate that visuomotor synchronization improves dramatically with compatible
      spatial information. However, an auditory advantage in sensorimotor
      synchronization persists.

PMID- 20695699
TI  - The line motion illusion: the detection of counterchanging edge and surface
      contrast.
AB  - A version of the line motion illusion (LMI) occurs when one of two adjacent
      surfaces changes in luminance; a new surface is perceived sliding in front of the
      initially presented surface. Previous research has implicated high-level
      mechanisms that can create or modulate LMI motion via feedback to lower-level
      motion detectors. It is shown here that there also is a non-motion-energy,
      feedforward basis for LMI motion entailing the detection of counterchange, a
      spatial pattern of motion-specifying stimulus information that combines changes
      in edge contrast with oppositely signed changes in background-relative surface
      contrast. It was concluded that (1) in addition to LMI motion, edge/surface
      counterchange could be the basis for perceiving continuous object motion, (2)
      counterchange detection is the likely basis for third-order motion perception (Lu
      & Sperling, 1995a), and (3) motion energy and counterchange mechanisms could be
      composed of different arrangements of the same spatial and temporal filters, the
      former detecting motion at a single location, the latter detecting the motion
      path between pairs of locations.

PMID- 20695700
TI  - Infants' perception of affordances of slopes under high- and low-friction
      conditions.
AB  - Three experiments investigated whether 14- and 15-month-old infants use
      information for both friction and slant for prospective control of locomotion
      down slopes. In Experiment 1, high- and low-friction conditions were interleaved
      on a range of shallow and steep slopes. In Experiment 2, friction conditions were
      blocked. In Experiment 3, the low-friction surface was visually distinct from the
      surrounding high-friction surface. In all three experiments, infants could walk
      down steeper slopes in the high-friction condition than they could in the low
      friction condition. Infants detected affordances for walking down slopes in the
      high-friction condition, but in the low-friction condition, they attempted
      impossibly slippery slopes and fell repeatedly. In both friction conditions, when
      infants paused to explore slopes, they were less likely to attempt slopes beyond
      their ability. Exploration was elicited by visual information for slant
      (Experiments 1 and 2) or by a visually distinct surface that marked the change in
      friction (Experiment 3).

PMID- 20695702
TI  - The role of expertise in tool use: skill differences in functional action
      adaptations to task constraints.
AB  - Tool use can be considered a particularly useful model to understand the nature
      of functional actions. In 3 experiments, tool-use actions typified by stone
      knapping were investigated. Participants had to detach stone flakes from a flint
      core through a conchoidal fracture. Successful flake detachment requires
      controlling various functional parameters simultaneously. Accordingly, our goals
      were twofold: (a) to examine the regulation of kinetic energy by varying the
      properties of the hammers and the goal, and (b) to characterize the difference in
      action regulation across skill levels. All groups were able to modify their
      actions according to changes in task goals, but only experts displayed fine
      tuning to functional parameters (i.e., regulate actions according to changes in
      hammer weight in a manner that left kinetic energy unchanged). Expertise is
      considered to depend on the identification of the interactions between functional
      parameters.

PMID- 20695701
TI  - The paired-object affordance effect.
AB  - We demonstrate that right-handed participants make speeded classification
      responses to pairs of objects that appear in standard co-locations for right
      handed actions relative to when they appear in reflected locations. These effects
      are greater when participants "weight" information for action when deciding if 2
      objects are typically used together, compared with deciding if objects typically
      occur in a given context. The effects are enhanced, and affect both types of
      decision, when an agent is shown holding the objects. However, the effects are
      eliminated when the objects are not viewed from the first-person perspective and
      when words are presented rather than objects. The data suggest that (a)
      participants are sensitive to whether objects are positioned correctly for their
      own actions, (b) the position information is coded within an egocentric reference
      frame, (c) the critical representation involved is visual and not semantic, and
      (d) the effects are enhanced by a sense of agency. The results can be interpreted
      within a dual-route framework for action retrieval in which a direct visual route
      is influenced by affordances for action.

PMID- 20695703
TI  - Acquisition of automatic imitation is sensitive to sensorimotor contingency.
AB  - The associative sequence learning model proposes that the development of the
      mirror system depends on the same mechanisms of associative learning that mediate
      Pavlovian and instrumental conditioning. To test this model, two experiments used
      the reduction of automatic imitation through incompatible sensorimotor training
      to assess whether mirror system plasticity is sensitive to contingency (i.e., the
      extent to which activation of one representation predicts activation of another).
      In Experiment 1, residual automatic imitation was measured following incompatible
      training in which the action stimulus was a perfect predictor of the response
      (contingent) or not at all predictive of the response (noncontingent). A
      contingency effect was observed: There was less automatic imitation indicative of
      more learning in the contingent group. Experiment 2 replicated this contingency
      effect and showed that, as predicted by associative learning theory, it can be
      abolished by signaling trials in which the response occurs in the absence of an
      action stimulus. These findings support the view that mirror system development
      depends on associative learning and indicate that this learning is not purely
      Hebbian. If this is correct, associative learning theory could be used to
      explain, predict, and intervene in mirror system development.

PMID- 20695704
TI  - The object-based Simon effect: grasping affordance or relative location of the
      graspable part?
AB  - Reaction time is often shorter when the irrelevant graspable handle of an object
      corresponds with the location of a keypress response to the relevant attribute
      than when it does not. This object-based Simon effect has been attributed to an
      affordance for grasping the handle with the hand to the same side. Because a
      grasping affordance should differentially affect keypress responses only when
      they are made with different hands, we conducted three experiments that measured
      the object-based Simon effect for frying pan stimuli using between- and within
      hand response sets. When the relevant stimulus dimension was color, neither the
      object-based Simon effect nor the location-based Simon effect varied across
      response sets. When upright-inverted orientation judgments were made for the
      frying pan and for nongraspable stimuli derived from it, there again was no
      significant difference in size of the between- and within-hand Simon effects for
      any of the stimuli. The results provide evidence that the Simon effect for
      graspable frying pan stimuli is because of relative location of the handle and
      not to a grasping affordance.

PMID- 20695705
TI  - Learning to perceive the affordance for long-distance throwing: smart mechanism
      or function learning?
AB  - Bingham, Schmidt, & Rosenblum, (1989) showed that people are able to select, by
      hefting balls, the optimal weight for each size ball to be thrown farthest. We
      now investigate function learning and smart mechanisms as hypotheses about how
      this affordance is perceived. Twenty-four unskilled adult throwers learned to
      throw by practicing with a subset of balls that would only allow acquisition of
      the ability to perceive the affordance if hefting acts as a smart mechanism to
      provide access to a single information variable that specifies the affordance.
      Participants hefted 48 balls of different sizes and weights and judged
      throwability. Then, participants, assigned to one of four groups, practiced
      throwing (three groups with vision and one without) for a month using different
      subsets of balls. Finally, hefting and throwing were tested again with all the
      balls. The results showed: (1) inability to detect throwability before practice,
      (2) throwing improved with practice, and (3) participants learned to perceive the
      affordance, but only with visual feedback. These results indicated that the
      affordance is perceived using a smart mechanism acquired while learning to throw.

PMID- 20695706
TI  - Cross-modal face identity aftereffects and their relation to priming.
AB  - We tested the magnitude of the face identity aftereffect following adaptation to
      different modes of adaptors in four experiments. The perceptual midpoint between
      two morphed famous faces was measured pre- and post-adaptation. Significant
      aftereffects were observed for visual (faces) and nonvisual adaptors (voices and
      names) but not nonspecific semantic information (e.g., occupations). Aftereffects
      were also observed following imagination and adaptation to an associated person.
      The strongest aftereffects were found adapting to facial caricatures. These
      results are discussed in terms of cross-modal adaptation occurring at various
      loci within the face-recognition system analogous to priming.

PMID- 20695707
TI  - Tight coupling between positive and reversed priming in the masked prime
      paradigm.
AB  - When associations between certain visual stimuli and particular actions are
      learned, those stimuli become capable of automatically and unconsciously
      activating their associated action plans. Such sensorimotor priming is assumed to
      be fundamental for efficient responses, and can be reliably measured in masked
      prime studies even when the primes are not consciously perceived. However, when
      the delay between prime and target is increased, reversed priming effects are
      often found instead (the negative compatibility effect, NCE). The main accounts
      of the NCE assume that it too is a sensorimotor phenomenon, predicting that it
      should occur only when the initial positive priming phase also occurs.
      Alternatively, reversed priming may reflect a perceptual process entirely
      independent from positive motor priming (which is simply evident at a different
      temporal delay), in which case no dependency is expected between the NCE and
      positive priming. We tested these predictions while new sensorimotor associations
      were learned, and found a remarkable symmetry between positive and reversed
      priming during all such learning phases, supporting the idea that reversed
      priming is a sensorimotor process that automatically follows the positive priming
      phase.

PMID- 20695708
TI  - Interpreting chicken-scratch: lexical access for handwritten words.
AB  - Handwritten word recognition is a field of study that has largely been neglected
      in the psychological literature, despite its prevalence in society. Whereas
      studies of spoken word recognition almost exclusively employ natural, human
      voices as stimuli, studies of visual word recognition use synthetic typefaces,
      thus simplifying the process of word recognition. The current study examined the
      effects of handwriting on a series of lexical variables thought to influence
      bottom-up and top-down processing, including word frequency, regularity,
      bidirectional consistency, and imageability. The results suggest that the natural
      physical ambiguity of handwritten stimuli forces a greater reliance on top-down
      processes, because almost all effects were magnified, relative to conditions with
      computer print. These findings suggest that processes of word perception
      naturally adapt to handwriting, compensating for physical ambiguity by increasing
      top-down feedback.

PMID- 20695709
TI  - Evidence from visuomotor adaptation for two partially independent visuomotor
      systems.
AB  - Visual information can specify spatial layout with respect to the observer
      (egocentric) or with respect to an external frame of reference (allocentric).
      People can use both of these types of visual spatial information to guide their
      hands. The question arises if movements based on egocentric and movements based
      on allocentric visual information comprise 2 independent visuomotor systems. In
      the experiments reported here, we used visuomotor adaptation to address this
      question. In an adaptation phase, subjects received distorted-visual feedback
      about their hand movements (17 degrees rotation and 110% amplitude stretch). In a
      testing phase (no-visual feedback), we measured how behavior changes in response
      to the distorted-visual feedback. During adaptation and testing, we used 2 tasks
      that required processing of either egocentric or allocentric visual information.
      The results show that behavioral changes are significantly larger when the same
      task is used during testing and adaptation, compared to when the task is
      switched. The findings suggest that the human brain employs 2 partially
      independent visuomotor systems that rely on different types of visual spatial
      information.

PMID- 20695710
TI  - Perceptual and attentional influences on continuous 2:1 and 3:2 multi-frequency
      bimanual coordination.
AB  - Two experiments were conducted to determine if multi-frequency (2:1 and 3:2)
      coordination between the limbs is enhanced when integrated feedback is provided
      in the form of Lissajous plots, attention demands are reduced, and attempts to
      consciously coordinate the limbs are not encouraged. To determine the influence
      of vision of the limbs, covered and uncovered limb groups were provided online
      Lissajous feedback. To determine the impact of the Lissajous feedback, a control
      group that was not provided Lissajous feedback was also tested. The data
      indicated remarkably effective performances after 5 min of practice when limbs
      were covered and Lissajous feedback was provided. When Lissajous feedback was
      provided and vision of the limbs was permitted, performance deteriorated.
      Performance by the group not provided Lissajous feedback was quite poor. The
      findings suggest that some of the difficulty associated with producing difficult
      bimanual coordination patterns are due to the less than optimal perceptual
      information available in various testing situations and the attentional focus
      imposed by the participant.

PMID- 20695711
TI  - Action selection in complex routinized sequential behaviors.
AB  - We report two experiments in which errors and interaction latencies were recorded
      during routinization of hierarchically structured computer-based tasks.
      Experiment 1 demonstrates that action selection is slowed at subtask transitions,
      especially when selecting lower frequency actions. This frequency effect is
      compounded by concurrent performance of a secondary, attentionally demanding,
      task. Experiment 2 replicates these results in a more complex task and further
      demonstrates that the effects are reduced by experience. Several other factors
      were also found to affect latencies, including the availability of an external
      disambiguation cue and the temporal distance over which task context needs to be
      internally maintained. The results support a "dual-systems" account of action
      selection in which a "routine" system, sensitive to frequency, context, and
      experience, is selectively modulated by an attentionally demanding "nonroutine"
      system.

PMID- 20695713
TI  - A dual-process account of auditory change detection.
AB  - Listeners can be "deaf" to a substantial change in a scene comprising multiple
      auditory objects unless their attention has been directed to the changed object.
      It is unclear whether auditory change detection relies on identification of the
      objects in pre- and post-change scenes. We compared the rates at which listeners
      correctly identify changed objects with those predicted by change-detection
      models based on signal detection theory (SDT) and high-threshold theory (HTT).
      Detected changes were not identified as accurately as predicted by models based
      on either theory, suggesting that some changes are detected by a process that
      does not support change identification. Undetected changes were identified as
      accurately as predicted by the HTT model but much less accurately than predicted
      by the SDT models. The process underlying change detection was investigated
      further by determining receiver-operating characteristics (ROCs). ROCs did not
      conform to those predicted by either a SDT or a HTT model but were well modeled
      by a dual-process that incorporated HTT and SDT components. The dual-process
      model also accurately predicted the rates at which detected and undetected
      changes were correctly identified.

PMID- 20695712
TI  - Psychophysical reverse correlation with multiple response alternatives.
AB  - Psychophysical reverse-correlation methods such as the "classification image"
      technique provide a unique tool to uncover the internal representations and
      decision strategies of individual participants in perceptual tasks. Over the past
      30 years, these techniques have gained increasing popularity among both visual
      and auditory psychophysicists. However, thus far, principled applications of the
      psychophysical reverse-correlation approach have been almost exclusively limited
      to two-alternative decision (detection or discrimination) tasks. Whether and how
      reverse-correlation methods can be applied to uncover perceptual templates and
      decision strategies in situations involving more than just two response
      alternatives remain largely unclear. Here, the authors consider the problem of
      estimating perceptual templates and decision strategies in stimulus
      identification tasks with multiple response alternatives. They describe a
      modified correlational approach, which can be used to solve this problem. The
      approach is evaluated under a variety of simulated conditions, including
      different ratios of internal-to-external noise, different degrees of correlations
      between the sensory observations, and various statistical distributions of
      stimulus perturbations. The results indicate that the proposed approach is
      reasonably robust, suggesting that it could be used in future empirical studies.

PMID- 20695714
TI  - Compensation for coarticulation: disentangling auditory and gestural theories of
      perception of coarticulatory effects in speech.
AB  - According to one approach to speech perception, listeners perceive speech by
      applying general pattern matching mechanisms to the acoustic signal (e.g., Diehl,
      Lotto, & Holt, 2004). An alternative is that listeners perceive the phonetic
      gestures that structured the acoustic signal (e.g., Fowler, 1986). The two
      accounts have offered different explanations for the phenomenon of compensation
      for coarticulation (CfC). An example of CfC is that if a speaker produces a
      gesture with a front place of articulation, it may be pulled slightly backwards
      if it follows a back place of articulation, and listeners' category boundaries
      shift (compensate) accordingly. The gestural account appeals to direct attunement
      to coarticulation to explain CfC, whereas the auditory account explains it by
      spectral contrast. In previous studies, spectral contrast and gestural
      consequences of coarticulation have been correlated, such that both accounts made
      identical predictions. We identify a liquid context in Tamil that disentangles
      contrast and coarticulation, such that the two accounts make different
      predictions. In a standard CfC task in Experiment 1, gestural coarticulation
      rather than spectral contrast determined the direction of CfC. Experiments 2, 3,
      and 4 demonstrated that tone analogues of the speech precursors failed to produce
      the same effects observed in Experiment 1, suggesting that simple spectral
      contrast cannot account for the findings of Experiment 1.

PMID- 20695715
TI  - Priming in melody perception: tracking down the strength of cognitive
      expectations.
AB  - The musical priming paradigm has shown facilitated processing for tonally related
      over less-related targets. However, the congruence between tonal relatedness and
      the psychoacoustical properties of music challenges cognitive interpretations of
      the involved processes. Our goal was to show that cognitive expectations (based
      on listeners' tonal knowledge) elicit tonal priming in melodies independently of
      sensory components (e.g., spectral overlap). A first priming experiment minimized
      sensory components by manipulating tonal relatedness with a single note change in
      the melodies. Processing was facilitated for related over less-related target
      tones, but an auditory short-term memory model succeeded in simulating this
      effect, thus suggesting a sensory-based explanation. When the same melodies were
      played with pure tones (instead of piano tones), the sensory model failed to
      differentiate between related and less-related targets, while listeners' data
      continued to show a tonal relatedness effect (Experiment 2). The tonal priming
      effect observed here thus provides strong evidence for the influence of
      listeners' tonal knowledge on music processing. The overall findings point out
      the need for controlled musical material (and notably beyond tone repetition) to
      study cognitive components in music perception.

PMID- 20695716
TI  - Auditory stream segregation and the perception of across-frequency synchrony.
AB  - This study explored the extent to which sequential auditory grouping affects the
      perception of temporal synchrony. In Experiment 1, listeners discriminated
      between 2 pairs of asynchronous "target" tones at different frequencies, A and B,
      in which the B tone either led or lagged. Thresholds were markedly higher when
      the target tones were temporally surrounded by "captor tones" at the A frequency
      than when the captor tones were absent or at a remote frequency. Experiment 2
      extended these findings to asynchrony detection, revealing that the perception of
      synchrony, one of the most potent cues for simultaneous auditory grouping, is not
      immune to competing effects of sequential grouping. Experiment 3 examined the
      influence of ear separation on the interactions between sequential and
      simultaneous grouping cues. The results showed that, although ear separation
      could facilitate perceptual segregation and impair asynchrony detection, it did
      not prevent the perceptual integration of simultaneous sounds.

PMID- 20695717
TI  - Are fast interceptive actions continuously guided by vision? Revisiting Bootsma
      and van Wieringen (1990).
AB  - In an influential study, R. J. Bootsma and P. C. W. van Wieringen (1990) argued
      that 2 of their 5 participants used visual information continuously during the
      attacking forehand drive in table tennis, its brief duration vis-a-vis the
      visuomotor delay notwithstanding. The authors repeated Bootsma and van
      Wieringen's experiment and included a condition in which vision was obscured
      after drive initiation. The authors replicated most of Bootsma and van
      Wieringen's findings but found no significant differences between the full-vision
      and no-vision conditions, which goes against the interpretation of these findings
      as evidence for continuous visual guidance. A subsequent simulation study found
      that a single preprogrammed muscle stimulation pattern resulted in spatiotemporal
      convergence similar to that observed experimentally but not in other important
      behavioral characteristics. The results contain no indications that visual
      information that becomes available after drive initiation affects arm motion and
      suggest that a form of model-based predictive control is operative rather than
      continuous visual guidance.

PMID- 20695718
TI  - Top-level players' visual control of interceptive actions: Bootsma and van
      Wieringen (1990) 20 years later.
AB  - Using a two-step approach, Van Soest et al. (2010) recently questioned the
      pertinence of the conclusions drawn by Bootsma and Van Wieringen (1990) with
      respect to the visual regulation of an exemplary rapid interceptive action: the
      attacking forehand drive in table tennis. In the first step, they experimentally
      compared the movement behaviors of their participants under conditions with and
      without vision available during the execution of the drive. In the second step,
      through simulation they evaluated the extent to which a preprogrammed pattern of
      muscle stimulation acting on the dynamical characteristics of the musculoskeletal
      system could explain the patterns of movement observed, including the phenomena
      of kinematic convergence and compensatory variability. In this contribution, we
      show how methodological and conceptual shortcomings, pertaining to both parts of
      Van Soest et al.'s study, severely limit the impact of their findings. We argue
      that their conclusion-denying the possibility of visual regulation of rapid
      interceptive actions-cannot be upheld in the light of the existing evidence,
      while Bootsma and Van Wieringen's conclusion-in favor of the visual regulation of
      rapid interceptive actions in top-level players- still holds strong, even after
      20 years. Irrespective of the trends of the moment, we suggest that both
      appropriate experimentation and principled theorization need to be deployed
      before a model-based predictive architecture can be considered as a serious
      alternative to a (more parsimonious) information-based control architecture.

PMID- 20695720
TI  - Impact of aspirin, NSAIDs, warfarin, corticosteroids and SSRIs on the site and
      outcome of non-variceal upper and lower gastrointestinal bleeding.
AB  - OBJECTIVE: To assess the impact of increased use of low-dose aspirin, other non
      steroidal anti-inflammatory drugs (NSAIDs), warfarin, corticosteroids and
      selective serotonin re-uptake inhibitors (SSRIs) on the site and outcome of non
      variceal gastrointestinal (GI) bleeds. METHODS: Retrospective review of 731
      patients with peptic ulcer bleeds (PUBs), non-ulcer, non-variceal upper
      (NUUPGIBs) and lower GI bleeds (LGIBs) in 1984, 1994 and 2004 at Lund University
      Hospital, Sweden. Incidence and mortality rates, risk factors for fatal outcome
      and associations with different sites of GI bleeds were evaluated. RESULTS:
      Between 1984 and 2004, incidence of PUBs decreased from 62.0 to 32.1 per 100,000
      inhabitants (p<0.001). Incidence of NUUPGIBs (29.0-30.4 per 100,000) and LGIBs
      (45.5-43.2 per 100,000) was stable. The case-fatality rate ranged from 4-6%
      (p=0.65) for upper GI bleed to 1-8% (p=0.033) for LGIB. No drug impacted on fatal
      outcome. Aspirin, warfarin and SSRI users tended to suffer more severe GI bleeds
      than non-users of these drugs. When comparing non-ulcer GI bleeds with PUBs,
      aspirin (OR 0.56, 95% CI 0.38-0.82) was more strongly associated with PUBs,
      whereas SSRIs (OR 3.71, 95% CI 1.39-12.9) and corticosteroids (OR 2.8, 95% CI
      1.28-6.82) were more associated with non-ulcer GI bleeds after adjusting for age,
      gender and co-morbidity. CONCLUSION: Increased use of drugs that promote bleeding
      has not impacted on incidence and fatal outcome of non-variceal GI bleeds,
      although the severity of bleeding has increased. Aspirin is more strongly
      associated with PUBs, while corticosteroids and SSRIs are associated with non
      ulcer, non-variceal GI bleeds.

PMID- 20695721
TI  - Is portal hypertensive enteropathy an important additional cause of blood loss in
      portal hypertensive patients?
AB  - OBJECTIVE: Recently, mucosal changes of small bowel were defined by developing
      new imaging techniques including capsule endoscopy (CE) in portal hypertensive
      patients. However, the clinical impact of these changes is unknown. In this
      study, we aimed to determine the additional cause of blood loss in portal
      hypertensive patients. MATERIAL AND METHODS: A total of 444 portal hypertensive
      patients, hospitalized in our clinic between 2005 and 2007, were evaluated.
      Patients with obscure bleeding were enrolled to this prospective case-control
      study. CE was performed in 21 patients who met inclusion criteria. Gastroscopy,
      colonoscopy and computerized tomography/small bowel enema were performed in all
      patients. RESULTS: Fourteen cirrhotic and seven noncirrhotic portal hypertensive
      patients were enrolled to this study. Mean age of patients was 47.9+/-15.6 years,
      and 13 of 21 were male. Small bowel varices were found in 7 patients (1 active
      bleeding) and other mucosal abnormalities in 10 patients (vascular ectasia,
      erosion and edema, 1 active bleeding). Although two of them were normal, jejunal
      malignant mass was found in two patients (1 active bleeding). Of 21 patients, 19
      (90.5%) patients had portal hypertensive abnormalities (including varices).
      However, ileal varices rate was 57.1% (4 patients) in noncirrhotic portal
      hypertensive patients and 21.4% (3 patients) in cirrhotics. CONCLUSION: Ninety
      percent of patients had portal hypertensive abnormalities in small bowel and one
      third of them had small bowel varices. Small bowel varices and vascular ectasia
      were the main causes of obscure bleeding in portal hypertensive patients.

PMID- 20695722
TI  - Effects of terlipressin on water excretion after oral water load test in
      nonazotemic cirrhotic patients with ascites without hyponatremia.
AB  - OBJECTIVE: Impaired water excretion is a major prognostic factor in decompensated
      cirrhotic patients. We investigated if terlipressin improves water excretion
      after a water load test in nonazotemic cirrhotic patients with ascites without
      hyponatremia. METHODS: Fifteen patients (Child-Pugh B/C: 6/9) were studied after
      an oral water intake of 20 ml/kg within 40 min and water excretion over 5 h was
      measured at baseline: day 1, and after a bolus infusion (2 mg) of terlipressin:
      day 3. Mean arterial pressure (MAP) before and after water loading on day 1, and
      MAP, cardiac output (CO), and systemic vascular resistance (SVR) before and 1 h
      after terlipressin infusion on day 3, were evaluated. The 5-h creatinine
      clearance (ClCre), diuresis, and sodium excretion were also evaluated in each
      study day. RESULTS: The water load excreted on day 1 was significantly correlated
      with Child-Pugh score, ClCre, sodium excretion, and SVR. The water load excreted
      and diuresis increased significantly after terlipressin infusion in the 12
      patients that completed the study (48.3+/-3.3% vs. 39.5+/-4.9%; p=0.001 and
      2.51+/-0.21 vs. 2.06+/-0.29 ml/min; p=0.001, respectively); significant increases
      in ClCre and sodium excretion, a significant decrease in CO and significant
      increases in MAP and SVR were also noted. The changes in the percentage of water
      load excreted were significantly correlated with the changes in SVR and ClCre.
      CONCLUSIONS: Terlipressin increases water excretion during a water load test in
      nonazotemic cirrhotic patients without hyponatremia, suggesting that the
      administration of arterial vasoconstrictors could influence the prognosis of
      these patients.

PMID- 20695723
TI  - Determination of hepatic galactose elimination capacity using 2-[18F]fluoro-2
      deoxy-D-galactose PET/CT: reproducibility of the method and metabolic
      heterogeneity in a normal pig liver model.
AB  - OBJECTIVE: A PET method is developed for non-invasive measurement of regional
      metabolic liver function using the galactose analog 2-[18F]fluoro-2-deoxy-D
      galactose, FDGal. The aim of the present study was to determine the
      reproducibility of the method in pigs before translating it to human studies.
      MATERIAL AND METHODS: Five anesthetized pigs were studied twice within an
      interval of three days. A dynamic PET recording was performed with an injection
      of 100 MBq FDGal. Non-radioactive galactose was administered throughout the PET
      recordings to achieve near-saturated elimination kinetics. Arterial blood samples
      were collected for determination of blood concentrations of FDGal and galactose
      (c(gal)). Net metabolic clearance of FDGal, K(FDGal), was calculated from linear
      representation of data. The approximate maximal hepatic removal rate, V(max), of
      galactose (mmol/l tissue/min) was calculated as K(FDGal) c(gal). The estimates
      from Day 1 and Day 2 were compared and the coefficient of variation, COV, of the
      estimates calculated. Functional heterogeneity in normal pig liver was evaluated
      as COV of the tissue concentration of radioactivity during quasi steady-state
      metabolism. RESULTS: There was no significant difference between V(max) from Day
      1 and Day 2 (p = 0.38), and the reproducibility was good with a COV of 14% for
      the whole liver. In normal pig liver tissue, mean COV after an injection of FDGal
      was on average 15.6% with no day-to-day variation (p = 0.7). CONCLUSIONS: The
      novel FDGal PET method for determination of hepatic metabolic function has a good
      reproducibility and is promising for future human studies of regional liver
      function.

PMID- 20695724
TI  - In vitro drug responses in primary and metastatic colorectal cancers.
AB  - OBJECTIVE: Treatment of primary and metastatic colorectal carcinoma (CRC) based
      on 5-fluorouracil and folinic acid (5FU + FA), combined with irinotecan (FOLFIRI)
      or oxaliplatin (FOLFOX), provides response rates approaching 50% and a 20-month
      overall survival. Approximately 50% of CRC patients fail to respond to one or
      more drugs in either regimen, in many cases due to inherent or acquired drug
      resistance. We therefore characterized in vitro drug response and cross
      resistance in primary and metastatic CRC lesions. MATERIALS AND METHODS: The in
      vitro Extreme Drug Resistance Assay (EDRA) identifies extreme drug resistance
      (EDR) in solid tumors with over 99% accuracy and appears to mimic the clinical
      experience. We analyzed EDRA results from 4854 freshly resected CRC biopsies,
      including 1740 primary and 847 liver metastases. RESULTS: Primary and metastatic
      CRCs responded similarly to single agents 5FU + FA, irinotecan, and oxaliplatin.
      Primary and metastatic tumors expressing EDR to 5FU + FA demonstrated up to 58%
      cross-resistance to a variety of chemotherapy agents, with the lowest percentages
      for oxaliplatin (11% and 8%, respectively) and irinotecan (16% and 14%).
      Importantly, approximately 20% of tumors showed EDR to either FULFOX or FOLFIRI.
      CONCLUSION: Overall data analyses indicated that EDRA results obtained at initial
      diagnosis may be useful in guiding therapy selection for metastatic disease. Pre
      testing of tumors before treatment may provide essential drug cross-resistance
      information for better chemotherapy selection. Prospective clinical trials
      employing the EDRA are needed to substantiate these data.

PMID- 20695725
TI  - Comparison of monoclonal antibody-based stool antigen tests to determine the
      results of Helicobacter pylori eradication therapy.
AB  - OBJECTIVE: Stool antigen tests using monoclonal antibody are used to test the
      results of eradication therapy of Helicobacter pylori. A newly developed test
      using multiple monoclonal antibodies is considered to have higher sensitivity.
      The aim of this study was to examine whether monoclonal antibody-based stool
      antigen tests are equally applicable to determine the results of eradication
      therapy. MATERIALS AND METHODS: Stool specimens obtained from patients infected
      with H. pylori were diluted by human stool and tested by both Testmate pylori
      antigen enzyme immunoassay (TPAg EIA) and Premier Platinum HpSA PLUS (HpSA ELISA
      II). A total of 239 patients infected with H. pylori received eradication therapy
      and 5-8 weeks after finishing the treatment, stool samples were tested by TPAg
      EIA and HpSA ELISA II. On the same day of stool collection, all the patients
      received (13)C-urea breath test (UBT). RESULTS: After 5* dilution, optical
      density (OD) values of TPAg EIA were significantly reduced and three out of four
      stool specimens were tested negative after 10* dilution. By contrast, three
      specimens were tested positive even after 100* dilution by HpSA ELISA II. In the
      determination of eradication therapy, accordance between the two tests was 95.8%.
      Among 199 patients who tested negative by both stool antigen tests, 10 patients
      were positive by UBT. Overall accordance of TPAg EIA and HPSA ELISA II to UBT was
      91.2% and 95.4%, respectively (NS). CONCLUSIONS: Although reduction of OD values
      was seen in TPAg EIA, it did not seem to cause false negative results in stool
      samples after eradication therapy. Both TPAg EIA and HpSA ELISA II were equally
      useful to determine the results of eradication therapy comparing with UBT.

PMID- 20695726
TI  - Intermediate versus low or high prostate-specific antigen density level:
      comparison of cancer detection rate between 12- and 18-core prostate biopsy.
AB  - OBJECTIVE: To compare the diagnostic values of 12- and 18-core biopsies with
      respect to prostate-specific antigen (PSA) levels, prostate volumes (PV) and
      prostate-specific antigen density (PSAD). MATERIAL AND METHODS: Transrectal
      ultrasound-guided prostate biopsies were performed on 233 patients at a single
      tertiary academic center. Patients were prospectively randomized to the two
      protocols (12 or 18 core). The cancer detection rates achieved using these two
      methods were analyzed at different PSA levels, PVs and PSADs. RESULTS:
      Considering PSA level and PV simultaneously, patients were stratified into four
      groups (group A: PSA < 7 ng/ml and PV >= 45 cm(3); group B: PSA < 7 ng/ml and PV
      < 45 cm(3); group C: PSA >= 7 ng/ml and PV >= 45 cm(3); group D: PSA >= 7 ng/ml
      and PV < 45 cm(3)). 18-core biopsy had a higher cancer detection rate than 12
      core biopsy only in group C (55.2% vs 24.1%, p = 0.015). The 233 patients were
      also stratified into three groups according to PSAD level: the low PSAD group
      (PSAD < 0.15 ng/ml/cm(3)), the intermediate PSAD group (0.15 ng/ml/cm(3) <= PSAD
      < 0.25 ng/ml/cm(3)) and the high PSAD group (PSAD >= 0.25 ng/ml/cm(3)). In the
      intermediate PSAD group, 18-core biopsy had a higher cancer detection rate than
      12-core biopsy (54.2% vs 28.9%, p = 0.048). CONCLUSION: An 18-core biopsy is more
      useful than a 12-core biopsy for detecting prostate cancer in patients with high
      PSA and large PV, that is, with intermediate PSAD level.

PMID- 20695727
TI  - The pathological response and fate in the lung and pleura of chrysotile in
      combination with fine particles compared to amosite asbestos following short-term
      inhalation exposure: interim results.
AB  - The pathological response and translocation of a commercial chrysotile product
      similar to that which was used through the mid-1970s in a joint compound intended
      for sealing the interface between adjacent wall boards was evaluated in
      comparison to amosite asbestos. This study was unique in that it presents a
      combined real-world exposure and was the first study to investigate whether there
      were differences between chrysotile and amosite asbestos fibers in time course,
      size distribution, and pathological response in the pleural cavity. Rats were
      exposed by inhalation 6 h/day for 5 days to either sanded joint compound
      consisting of both chrysotile fibers and sanded joint compound particles (CSP) or
      amosite asbestos. Subgroups were examined through 1-year postexposure. No
      pathological response was observed at any time point in the CSP-exposure group.
      The long chrysotile fibers (L > 20 microm) cleared rapidly (T(1/2) of 4.5 days)
      and were not observed in the pleural cavity. In contrast, a rapid inflammatory
      response occurred in the lung following exposure to amosite resulting in Wagner
      grade 4 interstitial fibrosis within 28 days. Long amosite fibers had a T(1/2) >
      1000 days and were observed in the pleural cavity within 7 days postexposure. By
      90 days the long amosite fibers were associated with a marked inflammatory
      response on the parietal pleural. This study provides support that CSP following
      inhalation would not initiate an inflammatory response in the lung, and that the
      chrysotile fibers present do not migrate to, or cause an inflammatory response in
      the pleural cavity, the site of mesothelioma formation.

PMID- 20695728
TI  - Paralytic and lethal effects of Trichosanthes dioica root extracts in
      experimental worms.
AB  - CONTEXT: Trichosanthes dioica Roxb. (Cucurbitaceae), called pointed gourd in
      English, is a dioecious climber and its roots are traditionally used in India as
      a hydrogouge cathartic, tonic, and febrifuge, and in the treatment of jaundice,
      anasarca, and ascites. OBJECTIVE: To evaluate the in vitro effects of different
      solvent extracts of T. dioica root in experimental worms, viz. annelids and
      nematodes. MATERIALS AND METHODS: The in vitro paralytic and lethal effects of
      defatted dichloromethane (DCTD), methanol (METD), and aqueous (AQTD) extracts of
      T. dioica root were evaluated against Pheretima posthuma (Annelida) and Ascaridia
      galli (Nematoda) by keeping the worms in different concentrations of each test
      extract under specific experimental conditions followed by determination of mean
      paralysis and lethal times. Albendazole was used as the reference drug. RESULTS
      AND DISCUSSION: All the extracts demonstrated concentration-dependent paralytic
      and lethal effects on P. posthuma and lethal effects on A. galli. The DCTD was
      found to be the most potent followed by the METD and AQTD. A. galli was found to
      be more sensitive than P. posthuma against all extracts, indicating T. dioica
      root as an effective nematocide. CONCLUSION: The present study establishes the in
      vitro wormicidal property of T. dioica root extracts against the experimental
      worms, showing promising nematocidal (and hence anthelmintic) potential.

PMID- 20695729
TI  - Antinociceptive and anti-inflammatory effects of Costus spicatus in experimental
      animals.
AB  - CONTEXT: Costus spicatus Swartz (Costaceae), commonly called "cana-do-brejo'" in
      Brazil's northeast, is a medicinal plant found in wet coastal forests. In folk
      medicine an infusion of the aerial parts is taken to treat inflammation and pain.
      OBJECTIVE: The methanol extract obtained from the leaves of Costus spicatus
      (MECs) was evaluated for antinociceptive and anti-inflammatory activities.
      METHODS: Analgesic and anti-inflammatory activities were studied by measuring
      nociception through acetic acid, formalin, and hot-plate tests, while
      inflammation was induced by carrageenan. All experiments were conducted with
      experimental animals. RESULTS AND DISCUSSION: Following oral administration, MECs
      (100, 200, and 400 mg/kg) significantly reduced the number of writhes (52.8,
      43.1, and 55.3%, respectively) in the writhing test and the number of paw licks
      during phase 1 (61.9, 54.1, and 92.1%) and phase 2 (62.5, 82.9, and 98.1%, all
      doses) during the formalin test when compared to the control group animals. The
      reaction time during the hot-plate test was increased significantly and was dose
      dependent, whereas pretreatment with naloxone rigorously reduced the analgesic
      potential of MECs, which suggested participation of the opioid system in the
      modulation of pain induced by MECs. Such results were unlikely to be provoked by
      motor abnormality, as MECs-treated mice did not exhibit any performance
      alteration during the Rota-rod test. The administration of 200 and 400 mg/ kg
      (i.p.) of MECs exhibited an anti-inflammatory effect during the carrageenan test,
      which was based on interference with inflammatory mediator synthesis. CONCLUSION:
      We conclude that MECs has antinociceptive and anti-inflammatory activities in
      rodents.

PMID- 20695730
TI  - Neuro-ophthalmology in Cuba. Introduction.

PMID- 20695731
TI  - Cuban epidemic optic neuropathy and its relationship to toxic and hereditary
      optic neuropathy.
AB  - The similarities and differences between toxic/nutritional and hereditary optic
      neuropathy and the pathophysiologic mechanisms that they have in common are
      described. This is based on data from the epidemic suffered in Cuba in 1992,
      which affected the optic nerves of many individuals and the experience of the
      authors in dealing with various toxic optic neuropathies, as well as Leber's
      hereditary optic neuropathy.

PMID- 20695732
TI  - Diagnosis and surgical treatment of orbital tumors.
AB  - Orbital disorders, especially tumors, are rare and may be dealt with by different
      specialists, making it difficult for any one group to gain substantial experience
      with these conditions. However, orbital tumors, like many other rare diseases,
      are optimally managed by those with the greatest expertise. In this article, we
      review our diagnostic and therapeutic experience managing 172 patients, 103 who
      required surgery, over a 17-year period. In particular, we comment on our
      surgical techniques, which became less invasive during this time.

PMID- 20695733
TI  - Ischemic optic neuropathy.
AB  - Anterior ischemic optic neuropathy (AION) is a common cause of visual loss in
      patients over 50 years of age. Optical coherence tomography has provided new
      information which may have implications regarding future approaches to
      management.

PMID- 20695734
TI  - Microperimetry in the study of neuro-ophthalmic diseases.
AB  - Microperimetry is useful for the diagnosis of disorders of the optic nerve,
      especially when associated with central visual field defects. This technique
      supplements and improves the psychophysical evaluation of optic neuropathy.

PMID- 20695735
TI  - Optical coherence tomography for neuro-ophthalmologic diagnoses.
AB  - OCT is probably one of the most revolutionary technologies that has appeared in
      ophthalmology in recent years. We are still trying to understand and clarify the
      use of OCT in neuro-ophthalmology. In this article we share our experience using
      various OCT devices over the last ten years, as well as the experience of others
      as reported in the literature.

PMID- 20695736
TI  - Multifocal electroretinography.
AB  - Multifocal electroretinography (mfERG) provides functional and objective evidence
      of retinal dysfunction. We have found mfERG to be especially useful in the
      management of occult outer retinopathy and Stargardt's disease.

PMID- 20695737
TI  - Breath testing and antibiotics for possible bacterial overgrowth in irritable
      bowel syndrome.

PMID- 20695740
TI  - Development and progression of gastroesophageal varices in patients with chronic
      hepatitis C.
AB  - Hepatitis C virus infection is the leading cause of chronic liver disease in the
      western world. Chronic liver diseases may cause, through portal hypertension, the
      development of gastroesophageal varices, which can then bleed. We assess the
      findings of a study aimed at identifying the incidence of de novo varix
      development and their progression in patients with chronic hepatitis C and
      advanced fibrosis. This study was a substudy of the Hepatitis C Antiviral Long
      Term Treatment against Cirrhosis (HALT-C) trial. The HALT-C trial was designed to
      determine whether pegylated interferon (PEG-IFN) at low dose can reduce the rate
      of disease progression in these patients. Approximately 26% of patients developed
      de novo varices and 35.2% of patients with varices at baseline had variceal
      progression or bleeding during the 4-year follow-up. The authors examine
      demographic, clinical, laboratory, virological, endoscopic and histological
      factors associated with the development and progression of gastroesophageal
      varices. PEG-IFN-alpha2a therapy did not reduce the risk of development or
      progression of gastroesophageal varices.

PMID- 20695743
TI  - Gram-negative bacterial endocarditis in adults: state-of-the-heart.
AB  - Gram-negative endocarditis due to HACEK bacteria (Haemophilus species,
      Actinobacillus, Cardiobacterium, Eikenella and Kingella species) and non-HACEK
      organisms is an infrequent occurrence but is associated with significant
      morbidity and mortality. Traditionally, non-HACEK Gram-negative endocarditis has
      been associated with injection drug use. However, emerging data from more
      contemporary cohorts suggest changing epidemiology and risk factors for Gram
      negative endocarditis, necessitating an updated review of this subject. Moreover,
      optimal management, including the need for surgical intervention, and strategies
      for the prevention of Gram-negative endocarditis need to be revisited.

PMID- 20695744
TI  - Management of Helicobacter pylori infection.
AB  - Helicobacter pylori is the cause of peptic ulcer, gastric cancer and gastric
      lymphoma. Diagnosis of H. pylori infection can be made using invasive and
      noninvasive tests. Invasive tests based on endoscopy, such as histology, are
      recommended when a gastric malignancy is suspected. Alternatively, noninvasive
      tests, such as the urea breath test and stool tests are useful for H. pylori
      diagnosis and follow-up. Triple therapy with either amoxicillin or metronidazole,
      clarithromycin and proton pump inhibitor given twice daily for 7-14 days is the
      recommended first-line treatment, after having checked the individual
      clarithromycin antimicrobial susceptibility. A triple therapy with levofloxacin,
      amoxicillin and proton pump inhibitor for 10-14 days should be used as second
      line treatment, where the strains are susceptible to fluoroquinolone.
      Alternatively, bismuth-based quadruple therapy is recommended.

PMID- 20695745
TI  - Emerging trends in antibiotic use in US hospitals: quality, quantification and
      stewardship.
AB  - Three major trends in antibiotic use in US hospitals have emerged over the last
      few years: antibiotics as quality metrics, persistent use of different measures
      of antibiotic consumption and the emergence of antibiotic stewardship programs.
      Compared with Europe, where approaches are heterogeneous but generally
      consistent, the USA currently lacks the infrastructure to monitor antibiotic
      resistance and antibiotic consumption locally. Both have implemented programmatic
      strategies for prudent antibiotic use. The USA appears to have implemented
      processes more systematically to measure the quality of antibiotic use.

PMID- 20695746
TI  - Cytomegalovirus-associated renal allograft rejection: new challenges for
      antiviral preventive strategies.
AB  - The adverse impact of cytomegalovirus (CMV) infection after solid organ
      transplantion is currently believed to be mediated primarily by its
      immunomodulatory effects. There is a large body of evidence showing that both CMV
      disease and asymptomatic viremia are independent risk factors for the development
      of allograft rejection. The aim of this article is to summarize mechanisms
      whereby CMV is involved in the development and progression of allograft
      rejection, with particular emphasis on renal transplant recipients. The article
      will also address the potential of anti-CMV preventive protocols designed to
      favorably affect the incidence of allograft rejection.

PMID- 20695747
TI  - Current treatment of Crimean-Congo hemorrhagic fever in children.
AB  - Crimean-Congo hemorrhagic fever (CCHF) is a fatal viral hemorrhagic fever and is
      usually transmitted to humans by tick bite, or exposure to infected blood or
      tissues of infected livestock or humans. Although children can be infected with
      the CCHF virus, infection is unusual in the younger age group. Early diagnosis
      and treatment of CCHF infection is critical to the survival of patients and the
      control of the disease. In this article, we underline current therapeutic
      approaches to CCHF infection in children.

PMID- 20695748
TI  - Current diagnosis and treatment of visceral leishmaniasis.
AB  - Human visceral leishmaniasis (VL), a potentially fatal disease, is most prevalent
      in the Indian subcontinent, East Africa and South America. Definite diagnosis and
      effective treatment are the primary needs for the control of VL. Diagnosis of VL
      has typically relied on microscopic examination of bone marrow/splenic aspirate,
      but serology and molecular methods are now better alternatives. The conventional
      drugs for treatment of VL have limitations including unresponsiveness, relapse,
      specific toxicities and parenteral administration lasting for long durations.
      Moreover, they are less effective in HIV-VL-coinfected patients. Registration of
      miltefosine and paromomycin, and preferential pricing of AmBisome has offered
      more choices for monotherapy and combination therapy for VL. Combination therapy
      will increase treatment efficacy and prevent the development of resistance. In
      addition, active case finding and vector control strategies will also have a
      positive impact in the control of VL. This article critically addresses the
      currently available diagnostic and treatment regimens for the control of VL.

PMID- 20695749
TI  - Congenital transmission of Chagas disease: a clinical approach.
AB  - Chagas disease is caused by the protozoan Trypanosoma cruzi and is an endemic
      zoonosis in the American continent. Thanks to the successful implementation of
      national programs for reducing the vectorial infestation and the strict control
      of blood-borne transmission of Chagas disease, the relative importance of
      congenital transmission has recently increased. Nowadays, in areas without
      vectorial transmission, congenital transmission has become the main way by which
      the disease has spread. This article reviews current knowledge on Chagas disease,
      focusing on the congenital transmission route. The public health implications of
      the increasing number of T. cruzi-infected immigrants and congenital transmission
      in nonendemic areas is also analyzed.

PMID- 20695750
TI  - Characteristics of pathogenic fungi and antifungal therapy in cystic fibrosis.
AB  - A defective mucociliary clearance facilitates colonization with bacteria and
      fungal spores in cystic fibrosis patients. Yeasts and molds are cultured from the
      cystic fibrosis respiratory tract and often their clinical relevance is unknown.
      Candida spp. are the most commonly isolated yeasts, whereas Aspergillus spp.,
      Scedosporium apiospermum, as well as Exophiala dermatitidis in some countries,
      are the most frequent molds recovered from respiratory specimens. Molecular
      biotyping studies have revealed that some fungal genotypes are capable of
      chronically colonizing the airways. Persistent Aspergillus fumigatus infection is
      associated with an increased risk of pulmonary exacerbations requiring
      hospitalization. The prevalence of non-Aspergillus molds may be underestimated
      due to overgrowth of Pseudomonas and Aspergillus spp. on routine media. Allergic
      bronchopulmonary aspergillosis is usually treated by oral steroids and an
      antifungal azole drug. Interactions with the co-medication have to be considered.
      A small number of antifungal pharmacokinetic studies indicate a high inter
      subject variability for itraconazole, voriconazole and posaconazole, and
      therefore therapeutic drug monitoring is recommended.

PMID- 20695752
TI  - Efficacy assessment of interferon-alpha-engineered mesenchymal stromal cells in a
      mouse plasmacytoma model.
AB  - Bone marrow mesenchymal stromal cells (BM-MSCs) may survive and proliferate in
      the presence of cycling neoplastic cells. Exogenously administered MSCs are
      actively incorporated in the tumor as stromal fibroblasts, thus competing with
      the local mesenchymal cell precursors. For this reason, MSCs have been suggested
      as a suitable carrier for gene therapy strategies, as they can be genetically
      engineered with genes encoding for biologically active molecules that can inhibit
      tumor cell proliferation and enhance the antitumor immune response. We used BM
      MSCs engineered with the murine interferon-alpha (IFN-alpha) gene (BM-MSCs/IFN
      alpha) to assess in a mouse plasmacytoma model the efficacy of this approach
      toward neoplastic plasma cells. We found that IFN-alpha can be efficiently
      produced and delivered inside the tumor microenvironment. Subcutaneous multiple
      administration of BM-MSCs/IFN-alpha significantly hampered the tumor growth in
      vivo and prolonged the overall survival of mice. The antitumor effect was
      associated with enhanced apoptosis of tumor cells, reduction in microvessel
      density, and ischemic necrosis. By contrast, intravenous administration of BM
      MSCs/IFN-alpha did not significantly modify the survival of mice, mainly as a
      consequence of an excessive entrapment of injected cells in the pulmonary
      vessels. In conclusion, BM-MSCs/IFN-alpha are effective in inhibiting neoplastic
      plasma cell growth; however, systemic administration of engineered MSCs needs to
      be improved to make this approach potentially suitable for the treatment of
      multiple myeloma.

PMID- 20695753
TI  - Synthesis and in vitro antifungal evaluation of 2-(2,4-difluorophenyl)-1-[(1H
      indol-3-ylmethyl)methylamino]-3-(1H-1,2,4-triazol-1-yl)propan-2-ols.
AB  - We extended our previous studies based on the design of 1-[(1H-indol-5
      ylmethyl)amino]-2-phenyl-3-(1H-1,2,4-triazol-1-yl)propan-2-ols as antifungal
      agents toward the identification of new indol-3-ylmethylamino derivatives. The
      majority of these compounds exhibited antifungal activity against a Candida
      albicans strain (minimum inhibitory concentrations ranging from 199.0 to 381.0
      ng/mL) suggesting an inhibition of 14alpha-demethylase by sterol analysis
      studies, but are weaker inhibitors compared to their indol-5-ylmethylamino
      analogs.

PMID- 20695754
TI  - Urease activity and L-ascorbic acid.
AB  - In this work, we studied the behaviours of urease in the presence of l-ascorbic
      acid (AA) and dehydroascorbic acid (DHA) in different conditions. The
      inactivations of urease were carried out in an unbuffered and buffered system. We
      show that in the unbuffered system AA inactivated urease in a biphasic manner by
      denaturation brought about by AA-lowered pH. Further, we show that in the
      buffered system neither AA nor DHA themselves are inhibitors of urease. The
      inhibitory action of AA and DHA was revealed in the presence of Fe(3+) ions and
      most importantly, unlike reported in the literature, it was found to be primarily
      mediated by H(2)O(2). The resulting inhibition by DHA-Fe(3+) consisted of enzyme
      thiol oxidation and its effectiveness grew with increasing pH. The results may
      shed light on the roles of AA in therapies applied in ureolytic bacteria
      infections, notably those with Helicobacter pylori.

PMID- 20695755
TI  - The scenarios of shock in newborn infants.
AB  - Shock defines a complex dysfunction of organ perfusion, that produces a status of
      cellular energy failure, resulting from an insufficient supply of oxygen and
      nutrients to tissues. The diagnosis of shock is very difficult because of the
      lack of sufficiently sensitive and specific clinical criteria, and is
      substantially based on the demonstration of an arterial hypotension, an indicator
      unfit to detect the organ hypoperfusion. It determines the necessity of firmly
      introducing in the diagnostic run the functional echocardiography, the near
      infrared spectroscopy and the amplitude &#x2013; integrated
      electroencephalography, etc., in the monitoring of the critical newborn. In order
      to simplify the problem, the authors identify the clinical scenarios of the
      newborn's shock to enhance the different pathogenetic moments and to build up
      appropriate therapeutic algorithms, without forgetting that at present there is
      no evidence that treatment of shock improves outcomes, despite the large amount
      of the studies conducted on this topic.

PMID- 20695756
TI  - Palivizumab prophylaxis in 'late preterm' newborns.
AB  - In the last decades the preterm birth rate rose more than 20%, largely because of
      an increase among deliveries of 'late preterm' infants, i.e. those born at 34 to
      36 weeks gestational age. Late preterm infants are more susceptible to infection
      by pathogens, such as respiratory syncytial virus (RSV), possibly because of the
      immaturity of both the respiratory system and the immune system. As a
      consequence, similar risks of serious RSV illness have been observed in late
      preterm and preterm (born <= 32 wGA) infants, higher when compared with full-term
      infants. Prevention of RSV infection includes palivizumab, which is proven to be
      effective in reducing the overall hospitalization rate for RSV-induced
      bronchiolitis in preterm neonates. In order to maximize the cost-effectiveness of
      this preventive approach, the American Academy of Pediatrics (AAP) has suggested
      the administration of palivizumab to infants born between 32 0/7 and 34 6/7 wGA
      with at least one risk factor and born 3 months before or during RSV season.
      Because a variety of environmental and demographic traits may affect the severity
      of RSV epidemics in different Nations, a European risk scoring tool has been
      developed, based on the 'local' most important risk factors. Therefore,
      recommendations and guidelines must be modulated in each country, determining
      their appropriateness in the individual setting.

PMID- 20695757
TI  - Pharmacological neuroprotection after perinatal asphyxia.
AB  - Recent progress has provided us with several promising neuroprotective compounds
      to reduce perinatal hypoxic-ischemic (HI) brain injury. In the early post HI
      phase, therapies can be concentrated on ion channel blockage (Xenon), anti
      oxidation (allopurinol, 2-iminobiotin, and indomethacin), anti-inflammation
      (erythropoietin [EPO], melatonin), and anti-apoptosis (nuclear factor kappa B [NF
      &#x03BA;B]and c-jun N-terminal kinase [JNK] inhibitors); in the later phase,
      therapies should be targeted to promote neuronal regeneration by stimulation of
      neurotrophic properties of the neonatal brain (EPO, growth factors, stem cells
      transplantation). Combination of pharmacological interventions with moderate
      hypothermia, which is the only established therapy for post HI brain injury, is
      probably the next step to fight HI brain damage in the clinical setting. Further
      studies should be concentrated on more rational pharmacological strategies by
      determining the optimal time and dose to inhibit the various potentially
      destructive molecular pathways and/or to enhance endogenous repair meanwhile
      avoiding the adverse effects.

PMID- 20695758
TI  - MR imaging in cases of antenatal suspected appendicitis--a meta-analysis.
AB  - OBJECTIVE: Appendicitis is the most common surgical emergency in pregnancy. Acute
      appendicitis is often difficult to diagnose clinically, and concerns regarding
      antenatal CT imaging limit its use resulting in high false negative rates at
      laparotomy. MRI has recently been reported as a reasonable alternative to CT
      imaging in cases of suspected appendicitis. Our objective was to perform a meta
      analysis of recently published data regarding the utility of MR imaging in cases
      of antenatal suspected acute appendicitis. METHODS: We searched the PubMed
      database using keywords 'MRI', 'appendicitis', and 'pregnancy'. Five case series
      describing the role of MRI in cases of antenatal appendicitis were included. The
      sensitivity, specificity, positive, and negative predictive values were
      calculated. RESULTS: Two hundred twenty-nine patients were included in the study.
      In the first analysis in which non-diagnostic scans were excluded, the
      sensitivity, specificity, positive and negative predictive values of MRI for
      diagnosing appendicitis were 95.0%, 99.9%, 90.4%, and 99.5%, respectively. In the
      second analysis, which included non-diagnostic scans, the sensitivity,
      specificity, positive and negative predictive values were 90.5%, 98.6%, 86.3%,
      and 99.0%, respectively CONCLUSIONS: MR imaging may be useful in cases of
      suspected antenatal appendicitis. Data are still limited and larger prospective
      studies are necessary to confirm this finding.

PMID- 20695759
TI  - Investigation of the regenerative capacity of an acellular porcine medial
      meniscus for tissue engineering applications.
AB  - Previously, we have described the development of an acellular porcine meniscal
      scaffold. The aims of this study were to determine the immunocompatibility of the
      scaffold and capacity for cellular attachment and infiltration to gain insight
      into its potential for meniscal repair and replacement. Porcine menisci were
      decellularized by exposing the tissue to freeze-thaw cycles, incubation in
      hypotonic tris buffer, 0.1% (w/v) sodium dodecyl sulfate in hypotonic buffer plus
      protease inhibitors, nucleases, hypertonic buffer followed by disinfection using
      0.1% (v/v) peracetic, and final washing in phosphate-buffered saline. In vivo
      immunocompatibility was assessed after implantation of the acellular meniscal
      scaffold subcutaneously into galactosyltransferase knockout mice for 3 months in
      comparison to fresh and acellular tissue treated with alpha-galactosidase
      (negative control). The cellular infiltrates in the explants were assessed by
      histology and characterized using monoclonal antibodies against: CD3, CD4, CD34,
      F4/80, and C3c. Static culture was used to assess the potential of acellular
      porcine meniscal scaffold to support the attachment and infiltration of primary
      human dermal fibroblasts and primary porcine meniscal cells in vitro. The
      explants were surrounded by capsules that were more pronounced for the fresh
      meniscal tissue compared to the acellular tissues. Cellular infiltrates
      compromised mononuclear phagocytes, CD34-positive cells, and nonlabeled
      fibroblastic cells. T-lymphocytes were sparse in all explanted tissue types and
      there was no evidence of C3c deposition. The analysis revealed an absence of a
      specific immune response to all of the implanted tissues. Acellular porcine
      meniscus was shown to be capable of supporting the attachment and infiltration of
      primary human fibroblasts and primary porcine meniscal cells. In conclusion,
      acellular porcine meniscal tissue exhibits excellent immunocompatibility and
      potential for cellular regeneration in the longer term.

PMID- 20695760
TI  - Uterine contractility is strongly influenced by steroids and glucose metabolism:
      an in vitro study on bovine myometrium.
AB  - BACKGROUND: Energetic substrates and hormonal phase are important for uterine
      contractions. Etomoxir a muscle carnitine palmitoyltransferase-1 inhibitor, able
      to diverge uterine metabolic pathways towards glycolysis, facilitates glucose
      utilisation. The aim of this study was to evaluate its effect on uterine
      contractility in different hormonal situations. METHODS: Uterine samples were
      collected from 60 cows during follicular phase, luteal phase and pregnancy. The
      cows were slaughtered at a local abattoir. Longitudinal strips were mounted
      vertically in a 30-ml organ bath connected to an isometric force transducer.
      Contractions were recorded with an ink-writing polygraph. After the equilibration
      period, etomoxir was added to the organ bath at different concentrations. The
      amplitude and frequency of contractions were registered before and after addition
      of etomoxir. RESULTS: In 17 strips from pregnant cows, etomoxir increased the
      amplitude (p < 0.05) of contractions but not the frequency in comparison with
      basal conditions. In 15 strips from cows in the luteal phase, etomoxir increased
      the amplitude (p < 0.05) and frequency of contractions (p < 0.05 at 5 MUM and p <
      0.01 at 8 and 10 MUM). In 18 strips from cows in the follicular phase, etomoxir
      increased the frequency of contractions but not the amplitude (p < 0.01 at 5 MUM
      and p < 0.05 at 8 and 10 MUM). CONCLUSIONS: This study confirms the importance of
      glucose for uterine contractility and, moreover, it underlines different patterns
      of contraction with regard to the hormonal status.

PMID- 20695761
TI  - Evaluation of asymmetric dimethylarginine, nitric oxide levels and associated
      independent variables in obese and lean patients with polycystic ovarian
      syndrome.
AB  - OBJECTIVE: To evaluate the asymmetric dimethylarginine (ADMA) and nitric oxide
      (NO) levels in obese and lean patients with polycystic ovarian syndrome (PCOS)
      and find out their relation with hormonal and metabolic parameters. METHODS:
      Twenty-two obese, 18 lean patients with PCOS and 11 obese, 24 lean healthy
      control patients were enrolled prospectively. Plasma ADMA and NO levels and
      arginine/ADMA ratio were evaluated on 3rd day of menstrual cycle after at least
      10 h overnight fasting. RESULTS: Plasma ADMA, NO levels and arginine/ADMA ratio
      were similar in the groups. ADMA level did not correlate with the hormonal and
      metabolic parameters in patients with PCOS. However, NO correlated inversely with
      fasting insulin (r =  -0.353, p = 0.041) and homeostasis model of insulin
      resistance (HOMA-IR) (r =  -0.379, p = 0.027). Arginine/ADMA ratio also
      correlated inversely with fasting insulin (r =  -0.339, p = 0.050). In
      multinomial regression analysis the risk of low NO was associated independently
      with high fasting insulin (OR = 1.19, 95% CI 1.001-1.42, p = 0.049) and high HOMA
      IR in patients with PCOS (OR = 2.26, 95% CI 1.03-4.98, p = 0.042). CONCLUSIONS:
      Insulin resistance may be the underlying mechanism of endothelial dysfunction
      through NO pathway in PCOS.

PMID- 20695763
TI  - Scaffold-based transplantation of akt1-overexpressing skeletal myoblasts:
      functional regeneration is associated with angiogenesis and reduced infarction
      size.
AB  - Myoblast-based therapy can improve cardiac function after infarction and is
      conventionally performed by direct injection. A scaffold-based transfer could
      overcome injection-associated problems. In upgrading this approach we
      transplanted skeletal myoblasts (SkM) overexpressing the prosurvival gene Akt1.
      SkM were transfected with pcDNA3-huda-Akt1 and seeded on polyurethane scaffolds.
      These scaffolds were transplanted in rats 2 weeks after myocardial infarction.
      Hemodynamics were analyzed before therapy and 6 weeks later. Infarction size and
      capillary density were performed thereafter. Additional groups received
      injections of Akt1-transfected or untransfected myoblasts, scaffolds seeded with
      untransfected myoblasts, or sham operation. Deterioration of global systolic left
      ventricular function could be inhibited by all therapeutic approaches. In
      addition, transplantation of Akt1-transfected cells, either scaffold-based or
      injected, was superior with regard to systolic properties of the left ventricular
      wall. This effect was accompanied by smaller infarction sizes and angiogenesis.
      Scaffolds with untransfected myoblasts yielded also smaller infarctions than
      injections of untransfected myoblasts. Both Akt groups profited with regard to
      dP/dt(min). In contrast, other diastolic parameters pointed at impaired
      relaxation and stiffer myocardium especially in the Akt1-scaffold group. In
      conclusion, SkM overexpressing Akt1 can maintain myocardial function after
      infarction, reduce infarction size, and induce neovascularization. Scaffold-based
      cell transfer does not augment this reverse remodeling capacity.

PMID- 20695762
TI  - Neural activity in frontal cortical cell layers: evidence for columnar
      sensorimotor processing.
AB  - The mammalian frontal cortex (FCx) is at the top of the brain's sensorimotor
      hierarchy and includes cells in the supragranular Layer 2/3, which integrate
      convergent sensory information for transmission to infragranular Layer 5 cells to
      formulate motor system outputs that control behavioral responses. Functional
      interaction between these two layers of FCx was examined using custom-designed
      ceramic-based microelectrode arrays (MEAs) that allowed simultaneous recording of
      firing patterns of FCx neurons in Layer 2/3 and Layer 5 in nonhuman primates
      performing a simple go/no-go discrimination task. This unique recording
      arrangement showed differential encoding of task-related sensory events by cells
      in each layer with Layer 2/3 cells exhibiting larger firing peaks during
      presentation of go target and no-go target task images, whereas Layer 5 cells
      showed more activity during reward contingent motor responses in the task. Firing
      specificity to task-related events was further demonstrated by synchronized
      firing between pairs of cells in different layers that occupied the same
      vertically oriented "column" on the MEA. Pairs of cells in different layers
      recorded at adjacent "noncolumnar" orientations on the MEA did not show
      synchronized firing during the same task-related events. The results provide
      required evidence in support of previously suggested task-related sensorimotor
      processing in the FCx via functionally segregated minicolumns.

PMID- 20695764
TI  - Up-regulation of angiotensin-converting enzyme and angiotensin II type 1 receptor
      in irradiated rats.
AB  - PURPOSE: To investigate changes in cardiac functional parameters and the cardiac
      expression of angiotensin-converting enzyme (ACE), angiotensin II type 1 receptor
      (AT1), procollagen type I (proc-I) and transforming growth factor-beta1 (TGF
      beta1) in rats irradiated at heart. MATERIAL AND METHODS: Male Wistar rats were
      irradiated with a single dose of radiation (0, 5, 10 and 15 Gray [Gy]) delivered
      directly to the heart and the molecular evaluations were performed at various
      times post-irradiation (two days, 15 days and four months). The expression of
      ACE, AT1, proc-I and TGF-beta1 were analysed using Real Time-Polymerase Chain
      Reaction (RT-PCR) and/or Western blotting. Cardiac structural and functional
      alterations were investigated at the four-month time point by echocardiography
      and by quantitative methods (stereology). RESULTS: Rats irradiated with 15 Gy
      showed a modest reduction in the ejection fraction. Cardiac proc-I, TGF-beta1,
      ACE and AT1 were also measurably increased. CONCLUSIONS: Irradiated rat hearts
      show simultaneous elevations in renin-angiotensin system components AT1 and ACE
      and cardiac remodeling markers proc-I and TGF-beta1.

PMID- 20695766
TI  - Anti-argonaute2 (Ago2/Su) and -Ro antibodies identified by immunoprecipitation in
      primary anti-phospholipid syndrome (PAPS).
AB  - OBJECTIVES: Primary anti-phospholipid syndrome (PAPS) is an autoimmune condition
      defined by anti-phospholipid antibodies (aPL) and thrombotic or obstetric events.
      Some PAPS can evolve into systemic lupus erythematosus (SLE) during follow-up.
      Few studies systematically examined lupus autoantibodies and their clinical
      significance in PAPS. The aim of our study is to analyze the clinical and
      laboratory correlations with lupus-related autoantibodies, detected by
      immunoprecipitation (IP), a technique not yet systematically applied to
      investigate autoantibodies in this condition. METHODS: Sera from 52 PAPS patients
      were screened by indirect immunofluorescence (IIF) antinuclear antibodies (ANA),
      IP of 35S-labeled K562 cell extract, and ELISA [anti-Argonaute2 (Ago2, Su),
      60kRo, 52kRo, La, dsDNA)]. Anti-Ago2/Su positive sera were also tested for anti
      GW bodies (GWBs) by IIF double staining, using rabbit anti-Rck/p54 serum.
      RESULTS: First, 56% of PAPS patients (29/52) were ANA positive, mainly with
      speckled pattern. Anti-Ago2/Su antibodies were found in 13% (7/52), anti-Ro/SSA
      in 10% (5/52), anti-La in one case. The clinical profile of patients did not seem
      to be related to the presence of these antibody specificities. However, levels of
      IgG anti-beta2 glycoprotein I antibodies were lower in anti-Ago2/Su positive
      patients (p = 0.02). None of anti-Ago2/Su or -Ro patients developed SLE during a
      2-year follow-up. Ago2 is a key component of GWBs, however, only 1/7 anti-Ago2/Su
      serum showed a typical cytoplasmic GWBs staining. CONCLUSIONS: Anti-Ago2/Su and 
      Ro antibodies are the two autoantibodies detected by IP in our PAPS cohort.
      Clarifying why Ago2/Su and Ro are specific targets of autoimmunity may help to
      understand the mechanisms of autoantibody production.

PMID- 20695765
TI  - Leptin treatment confers clinical benefit at multiple stages of virally induced
      type 1 diabetes in BB rats.
AB  - The adipokine, leptin, regulates blood glucose and the insulin secretory function
      of beta cells, while also modulating immune cell function. We hypothesized that
      the dual effects of leptin may prevent or suppress the autoreactive destruction
      of beta cells in a virally induced rodent model of type 1 diabetes. Nearly 100%
      of weanling BBDR rats treated with the combination of an innate immune system
      activator, polyinosinic:polycytidylic acid (pIC), and Kilham rat virus (KRV)
      become diabetic within a predictable time frame. We utilized this model to test
      the efficacy of leptin in preventing diabetes onset, remitting new onset disease,
      and preventing autoimmune recurrence in diabetic rats transplanted with syngeneic
      islet grafts. High doses of leptin delivered via an adenovirus vector (AdLeptin)
      or alzet pump prevented diabetes in>90% of rats treated with pIC+KRV. The serum
      hyperleptinemia generated by this treatment was associated with decreased body
      weight, decreased non-fasting serum insulin levels, and lack of islet insulitis
      in leptin-treated rats. In new onset diabetics, hyperleptinemia prevented rapid
      weight loss and diabetic ketoacidosis, and temporarily restored euglycemia.
      Leptin treatment also prolonged the survival of syngeneic islets transplanted
      into diabetic BBDR rats. In diverse therapeutic settings, we found leptin
      treatment to have significant beneficial effects in modulating virally induced
      diabetes. These findings merit further evaluation of leptin as a potential
      adjunct therapeutic agent for treatment of human type 1 diabetes.

PMID- 20695767
TI  - Prevention, but not cure, of autoimmune diabetes in a NOD.scid transfer model by
      FTY720 despite effective modulation of blood T cells.
AB  - FTY720 modulates lymphocyte trafficking through blood (peripheral blood
      lymphocyte, PBL) and peripheral lymph nodes (PLN). Treatment with FTY720 causes
      retention of most blood lymphocytes in PLN. Long-term treatment can slow and/or
      prevent Type 1 diabetes (T1D) in the nonobese diabetic (NOD) mouse model. B and T
      cells are both affected by FTY720 binding to sphingosine-1-phosphate receptor 1
      (S1P1). However, little has been done to elucidate which T-cell subsets are
      differentially affected by FTY720 under healthy conditions, and how this affects
      disease pathogenesis in T1D. In healthy C57BL/6J (B6) mice, total CD4(+) and
      CD8(+) T-cell subsets were diminished by FTY720, but recently activated and
      memory subsets were spared and constituted significantly higher percentage of
      remaining T cells in blood. FTY720 also lowered PBL counts in NOD mice, but less
      severely than in B6 mice. This is consistent with a different ratio of naive,
      activated, and memory cells in NOD mice compared to those in B6 mice, as well as
      alterations in S1P1 and sphingosine-1-phosphate (S1P) levels in PBLs and blood of
      NOD mice, respectively. To address the functional consequences of PBL T-cell
      depletion, we studied the effects of FTY720 on disease progression in a timed
      adoptive transfer model of T1D. Continuous treatment with FTY720 eliminated T1D,
      if treatment was started before splenocyte transfer. FTY20 treatment started
      after disease onset slowed disease progression. The inability to fully suppress
      memory and effector T-cell circulation may explain why FTY720 is only partially
      effective in the NOD adoptive transfer model of T1D.

PMID- 20695768
TI  - Exon 6 variants carried on systemic lupus erythematosus (SLE) risk haplotypes
      modulate IRF5 function.
AB  - Interferon regulatory factor 5 (IRF5) regulates innate immune responses to viral
      infection. IRF5 genetic variants have been shown to be strongly associated with
      risk for systemic lupus erythematosus (SLE). Functional roles of IRF5 exon 6
      structural variants that occur as part of a SLE risk-associated haplotype,
      including a 30-bp in/del (in/del-10) and a 48-bp splice-site variant (SV-16),
      have not been established. In this study, we used IRF5-deficient cells
      overexpressing human IRF5 (hIRF5) variants to investigate the roles of exon 6
      in/del-10 and SV-16 in regulation of the apoptosis response, nuclear
      translocation, and ability to transactivate IRF5 responsive cytokines. We found
      that expression of IRF5 isoforms including either SV-16 or in/del-10 confers
      ability of IRF5 to impair the apoptotic response and correlates with reduced
      capacity for IRF5 nuclear translocation in MEFs after a DNA-damaging stimulus
      treatment. Interestingly, the presence or absence of both SV-16 and in/del-10
      results in abrogation of both the anti-apoptotic and enhanced nuclear
      translocation effects of IRF5 expression. Only cells expressing IRF5 bearing SV
      16 show increased IL-6 production upon lipopolysaccharide stimulation. MEFs
      expressing hIRF5 variants containing in/del-10 showed no significant difference
      from the control; however, cells carrying hIRF5 lacking both SV-16 and in/del-10
      showed reduced IL-6 production. Our overall findings suggest that exon 6 SV-16 is
      more potent than in/del-10 for IRF5-driven resistance to apoptosis and promotion
      of cytokine production; however, in/del-10 co-expression can neutralize these
      effects of SV-16.

PMID- 20695769
TI  - Potent antirheumatic activity of a new DNA vaccine targeted to B7-2/CD28
      costimulatory signaling pathway in autoimmune arthritis.
AB  - Rheumatoid arthritis is a proinflammatory autoimmune disease attributed to
      failure of both CD4(+)CD25(+) regulatory T (Tr) and CD8(+)CD28(-) suppressor T
      (Ts) cells to control autoreactive CD4(+)CD28(+) Th1 (Th1) and autoantibody
      producing B cells. Here we show a single intramuscular injection of our novel
      targeted DNA vaccine encoding Pseudomonas exotoxin A and costimulatory molecule
      B7-2 without autoantigens in a collagen-induced arthritis model simultaneously
      increased Tr and Ts cells and selectively decreased autoreactive Th1 cells. The
      vaccine induced a shift from Th1 to Th2 and Th3 cellular and cytokine profiles
      and a decrease in CD4(+)/CD8(+) cell ratios. Importantly, the vaccine showed
      potent antirheumatic activity by clinical and other examinations such as X-ray,
      histopathology, and anti-type II collagen IgG levels and was comparable to
      methotrexate, the current "gold standard" treatment. As an effective stimulator
      of both Tr and Ts cells and a specific suppressor of autoreactive Th1 cells, this
      vaccine is a promising therapeutic approach for rheumatoid arthritis.

PMID- 20695770
TI  - Effects of a monophasic combined oral contraceptive containing nomegestrol
      acetate and 17 beta-oestradiol on ovarian function in comparison to a monophasic
      combined oral contraceptive containing drospirenone and ethinylestradiol.
AB  - OBJECTIVE: To compare the effects on ovarian activity of two oral contraceptives
      containing nomegestrol acetate (NOMAC)/17 beta-oestradiol (E2) or drospirenone
      (DRSP)/ethinylestradiol (EE). METHODS: In this open-label, randomised, six-cycle
      study, 32 subjects using NOMAC/E2 (2.5-1.5 mg; 24/4-day regimen) were compared to
      16 subjects using DRSP/EE (3 mg-30 microg; 21/7-day regimen). Measurements
      included serum oestradiol, progesterone, follicle stimulating hormone (FSH) and
      luteinising hormone (LH), and ultrasonography of follicular diameter. RESULTS: No
      ovulations occurred during treatment. Progesterone was fully suppressed, with
      mean maximum values <2 nmol/l in both groups over all cycles. For NOMAC/E2, mean
      maximum follicular diameter decreased from 19.3 mm before treatment to between
      6.9 and 8.2 mm during treatment, with no subject having a follicular diameter
      >=15 mm. For DRSP/EE, a decrease from 19.6 to between 7.4 and 10.8 mm was
      observed, with two subjects (12.5%) having a maximum follicle diameter >=15 mm.
      These findings were consistent with observed FSH reductions; full suppression of
      LH surges was observed in both groups. Post-treatment return of ovulation in both
      groups occurred on average 21 days after the last active tablet intake.
      CONCLUSIONS: NOMAC/E2 achieves consistent ovulation inhibition, with suppressive
      effects on the ovaries at least similar to those of DRSP/EE.

PMID- 20695771
TI  - Hormonal contraception in women with the metabolic syndrome: a narrative review.
AB  - OBJECTIVE: The metabolic syndrome (MS) is a set of five cardiovascular and
      metabolic risk factors: elevated waist circumference, fasting plasma glucose,
      triglycerides and blood pressure; and reduced HDL-cholesterol. The prevalence of
      the MS is rising worldwide, and is linked to two diagnoses in young women:
      polycystic ovary syndrome (PCOS) and gestational diabetes mellitus (GDM).
      METHODS: This narrative review focuses on hormonal contraceptive choices
      available for women in Europe with features of the MS. RESULTS: The
      levonorgestrel-intrauterine system and progestogen-only pills containing
      desogestrel or levonorgestrel have no significant effects on MS parameters.
      Combined oestrogen-progestogen methods do not appear to increase waist
      circumference or the incidence of glucose intolerance in women with PCOS or a
      history of GDM; their effect on HDL-cholesterol and triglycerides is comparable
      with that observed in women without the MS, while the effect on blood pressure
      remains inconclusive. The etonogestrel implant does not affect body weight,
      triglycerides and blood pressure but mildly reduces insulin sensitivity and HDL
      cholesterol in healthy women. Depot medroxyprogesterone acetate increases body
      weight and truncal fat deposition, and lowers glucose tolerance in women with
      previous GDM. CONCLUSIONS: Low-dose hormonal contraception is safe for many women
      with the MS, but high-dose progestogens must be avoided.

PMID- 20695773
TI  - Osteogenic potential of mesenchymal stem cells on expanded
      polytetrafluoroethylene coated with both a poly-amino-Acid urethane copolymer and
      collagen.
AB  - We have developed an expanded polytetrafluoroethylene polymer (e-P) coated with
      both poly-amino-acid urethane copolymer and collagen (e-PPC) to be used for cell
      culture substrata. Rat mesenchymal stem cells (MSC) were cultured on the e-P and
      e-PPC polymers in the presence of dexamethasone. After 24 h, the MSC contacted
      well with the e-PPC surface and after 14 days, the MSC showed high levels of
      alkaline phosphatase activity, and calcium and bone-specific osteocalcin protein
      deposition. The MSC cultured on these polymers for 1 week were then implanted at
      rat subcutaneous sites and harvested after 4 weeks. Microcomputed tomography as
      well as histological analyses showed that any hard tissue could not be seen in
      implants of the MSC/e-P composites, whereas new bone formation could be detected
      in the MSC/e-PPC composites. These in vitro as well as in vivo results confirmed
      the importance of polymer surface to support the osteogenic differentiation,
      which resulted in new bone formation. The surface modification using poly-amino
      acid urethane copolymer and collagen together with tissue engineering technology
      might facilitate bone anchoring to the polymers for dental and orthopedic
      applications.

PMID- 20695772
TI  - Injectable and photopolymerizable tissue-engineered auricular cartilage using
      poly(ethylene glycol) dimethacrylate copolymer hydrogels.
AB  - In this study we investigated the histological, biochemical, and integrative
      features of the neocartilage using swine auricular chondrocytes photoencapsulated
      into two poly(ethylene glycol) dimethacrylate (PEGDM) copolymer hydrogels of a
      different degradation profile: degradable (PEG-4,5LA-DM) and nondegradable
      (PEGDM) macromers in molar ratios of 60:40 and 70:30. Integration of the
      engineered tissue with existing native cartilage was examined using an articular
      cartilaginous ring model. Experimental group samples (total n=96) were implanted
      subcutaneously into nude mice and harvested at 6, 12, and 18 weeks. Nonimplanted
      constructs (total n=16) were used as controls for quantification of DNA,
      glycosaminoglycan, and hydroxyproline. Histologically, neocartilage resembled
      both the cellular population and composition of the extracellular matrix of the
      native swine auricular cartilage. DNA content demonstrated that the
      photoencapsulated chondrocytes were capable of survival and proliferation over
      time. Both glycosaminoglycan and hydroxyproline contents appeared higher in the
      neotissue, which was supported by less degradable PEGDM hydrogel. Integration of
      neocartilage with surrounding native cartilage improved with time, resulting in
      the development of tight integration interface. PEGDM copolymer hydrogels can
      support in vivo chondrogenesis by photoencapsulating auricular chondrocytes.

PMID- 20695774
TI  - New pharmacotherapy for airway mucus hypersecretion in asthma and COPD: targeting
      intracellular signaling pathways.
AB  - Airway mucus hypersecretion is a pathophysiological feature of asthma and chronic
      obstructive pulmonary disease (COPD). The hypersecretion is associated with
      phenotypic changes in the airways, notably, increases in the number of surface
      epithelial goblet cells (hyperplasia) and in the size of the submucosal glands
      (hypertrophy). The hyperplasia and hypertrophy are associated with increased
      production of mucin, the gel-forming component of mucus. The excess mucus
      production contributes to morbidity and mortality in many patients, particularly
      in those with more severe disease. Although current pharmacotherapy is effective
      in clinical management of patients with stable asthma, severe asthma is poorly
      treated and there is no current drug treatment for COPD. In neither disease is
      there specific, effective pharmacotherapy for the hypersecretion. Consequently,
      identification of potential drug targets for treatment of hypersecretion in
      asthma and COPD is warranted. The inflammatory mediators and the associated
      intracellular signaling pathways underlying upregulation of mucin synthesis and
      development of goblet cell hyperplasia are gradually being elucidated. These
      include Th2 cytokines (predominantly IL-9 and IL-13), and IL-1 beta, tumor
      necrosis factor-alpha (TNF-alpha) and cyclooxygenase (COX)-2. IL-9 may act
      predominantly via calcium-activated chloride channels (CLCA), IL-13 via STAT-6
      and FOXA2, TNF-alpha via NF-kappaB, and IL-1 beta via COX-2. Epidermal growth
      factor receptor (EGF-R) signaling and FOXA2 appear to be convergent intracellular
      pathways for a number of inflammatory mediators, with EGF-R upregulated in the
      airways of asthmatic and COPD patients. Thus, preclinical studies have clearly
      identified a number of intracellular signaling pathways as possible targets for
      pharmacotherapy of airway mucus hypersecretion in asthma and COPD. Of these, the
      EGF-R and Th2 cytokine pathways may have the greatest potential for inhibition of
      excessive mucus production. However, because these targets are so often
      intimately involved with different aspects of airway (and systemic) homeostasis,
      there is potential for development of unwanted side effects with drug
      intervention. Thus, translation of the promising preclinical studies to the
      clinic will depend on development of drug moieties with low off-target activity.
      This may be accomplished by maximizing airway selectivity, which may be
      facilitated by appropriate delivery device design.

PMID- 20695775
TI  - Analysis of the soluble human tooth proteome and its ability to induce
      dentin/tooth regeneration.
AB  - While the soluble proteins of human teeth consist of various extracellular matrix
      and bioactive proteins, they have not yet been characterized fully. Moreover, the
      role they play in tooth regeneration is not clear. Analysis of the soluble
      proteins in human teeth by liquid chromatography-mass spectrometry revealed 147
      different ethylenediaminetetraacetic acid-soluble tooth proteins (ESTPs). Of
      these, 29 had not been shown previously to be present in human teeth. To
      determine their effect on the in vitro responses of dental pulp stem cells
      (DPSCs), DPSCs were cultured in ESTP-coated culture plates and three-dimensional
      scaffolds. The ESTPs significantly enhanced DPSC odontoblast differentiation and
      mineralization in vitro, but had only partial effect on bone marrow stem cells or
      adipose tissue stem cells. To test the effect of ESTPs on in vivo dentin and
      tooth formation, mouse embryonic tooth-forming primordia and xenogenic murine
      apical bud epithelium/human DPSC composites were treated with ESTPs before
      implantation under the renal capsule of ICR mice. ESTP treatment promoted the
      formation of morphologically normal teeth by the tooth-forming primordium regions
      and enhanced the development of a regular and large dentin structure by the
      composites. These observations suggest that human ESTPs contain dentinogenic
      proteins and can promote dentin and tooth formation.

PMID- 20695777
TI  - Cell-derived matrix enhances osteogenic properties of hydroxyapatite.
AB  - The study aimed to evaluate osteogenic properties of hydroxyapatite (HA) scaffold
      combined with extracellular matrix (ECM) derived in vitro from rat primary
      calvarial osteoblasts or dermal fibroblasts. The cellular viability, and the ECM
      deposited onto synthetic HA microparticles were assessed by MTT,
      Glycosaminoglycan, and Hydroxyproline assays as well as immunohistochemistry and
      scanning electron microscopy after 21 days of culture. The decellularized HA-ECM
      constructs were implanted in critical-sized calvarial defects of Sprague-Dawley
      rats, followed by bone repair and local inflammatory response assessments by
      histomorphometry and immunohistochemistry at 12 weeks postoperatively. We
      demonstrated that HA supported cellular adhesion, growth, and ECM production in
      vitro, and the HA-ECM constructs significantly enhanced calvarial bone repair
      (p<0.05, Mann-Whitney U-test), compared with HA alone, despite the significantly
      increased number of CD68+ macrophages, and foreign body giant cells (p<0.05, Mann
      Whitney U-test). Selective accumulation of bone sialoprotein, osteopontin, and
      periostin was observed at the tissue-HA interfaces. In conclusion, in vitro
      derived ECM mimics the native bone matrix, enhances the osteogenic properties of
      the HA microparticles, and might modulate the local inflammatory response in a
      bone repair-favorable way. Our findings highlight the ability to produce
      functional HA-ECM constructs for bone tissue engineering applications.

PMID- 20695776
TI  - Guiding epithelial cell phenotypes with engineered integrin-specific recombinant
      fibronectin fragments.
AB  - The extracellular matrix (ECM) provides important cues for directing cell
      phenotype. Cells interact with underlying ECM through cell-surface receptors
      known as integrins, which bind to specific sequences on their ligands. During
      tissue development, repair, and regeneration of epithelial tissues, cells must
      interact with an interstitial fibronectin (Fn)-rich matrix, which has been shown
      to direct a more migratory/repair phenotype, presumably through interaction with
      Fn's cell binding domain comprised of both synergy Pro-His-Ser-Arg-Asn (PHSRN)
      and Arg-Gly-Asp (RGD) sequences. We hypothesized that the Fn synergy site is
      critical to the regulation of epithelial cell phenotype by directing integrin
      specificity. Epithelial cells were cultured on Fn fragments displaying stabilized
      synergy and RGD (FnIII9'10), or RGD alone (FnIII10) and cell phenotype analyzed
      by cytoskeleton changes, epithelial cell-cell contacts, changes in gene
      expression of epithelial and mesenchymal markers, and wound healing assay. Data
      indicate that epithelial cells engage RGD only with alphav integrins and display
      a significant shift toward a mesenchymal phenotype due, in part, to enhanced
      transforming growth factor-beta activation and/or signaling compared with cells
      on the synergy containing FnIII9'10. These studies demonstrate the importance of
      synergy in regulating epithelial cell phenotype relevant to tissue engineering as
      well as the utility of engineered integrin-specific ECM fragments in guiding cell
      phenotype.

PMID- 20695778
TI  - Enhancement of chemotactic response to sodium acetate in the nematode
      Caenorhabditis elegans.
AB  - In this study, we investigated the chemotactic response of a wild-type (N2)
      nematode (Caenorhabditis elegans) to a water-soluble attractant, sodium acetate,
      after pre-exposure to the chemical. The chemotactic response to 1.0 M sodium
      acetate of the non-exposed control nematodes was lower than that of the nematodes
      that were pre-exposed to 1.0 M sodium acetate for 90 min (p < 0.05). The increase
      in the response to sodium acetate was observed up to 6 hr, but not at 12 hr after
      exposure. To clarify the mechanism of this enhancement of the chemotactic
      response, several mutants were used. The chemotactic response of pre-exposed tph
      1 and bas-1 mutants, whose main defect was serotonin secretion, was enhanced in
      comparison with that of the control mutants (p < 0.01). However, cat-1 and cat-2
      mutants, which are respectively defective in serotonin and dopamine secretion and
      dopamine secretion only, showed no enhancement of the chemotactic response to
      sodium acetate, even when pre-exposed to this chemical. When the cat-1 and cat-2
      mutants were pre-exposed to sodium acetate and bred in the presence of 40 mM
      dopamine, these mutants showed enhanced chemotactic response to sodium acetate (p
      < 0.05). These results suggest that the enhancement of chemotactic response to
      sodium acetate after pre-exposure to this chemical is modulated by dopaminergic
      neurotransmission.

PMID- 20695779
TI  - Implication of HpEts in gene regulatory networks responsible for specification of
      sea urchin skeletogenic primary mesenchyme cells.
AB  - The large micromeres of the 32-cell stage of sea urchin embryos are autonomously
      specified and differentiate into primary mesenchyme cells (PMCs), giving rise to
      the skeletogenic cells. We previously demonstrated that HpEts, an ets-related
      transcription factor, plays an essential role in the specification of PMCs in sea
      urchin embryos. In order to clarify the function of HpEts in the gene regulatory
      network involved in PMC specification, we analyzed the zygotic expression pattern
      and the cis-regulatory region of HpEts, and examined the activity of the HpEts
      protein as a transcription factor. Intron-based PCR reveals that zygotic
      expression of HpEts starts at the cleavage stage, and that the rate of
      transcription reaches maximum at the unhatched blastula stage. A series of
      progressive deletions of the fragments from -4.2 kbp to +1206 bp of the HpEts,
      which directs PMC-specific expression, caused a gradual decrease in the
      specificity, implying that coordination of several cis-regulatory elements
      regulates the expression in PMCs. A minimum cis-element required for the temporal
      expression is located within a 10 bp from -243 bp to -234 bp. The HpEts protein
      remains in the cytoplasm of entire embryonic cells in the cleavage stage. At the
      unhatched blastula stage, the HpEts protein translocates into the nucleus in
      presumptive PMCs. Transactivation assays demonstrate that the HpEts protein
      activates a promoter of Spicule Matrix Protein 50 (SM50), which is a target of
      HpEts, which binds to the regulatory region of SM50.

PMID- 20695780
TI  - Population divergence of Biwia zezera (Cyprinidae: Gobioninae) and the discovery
      of a cryptic species, based on mitochondrial and nuclear DNA sequence analyses.
AB  - Mitochondrial and nuclear DNA analyses were used to examine the native
      distribution range and population structure of Biwia zezera (Cyprinidae:
      Gobioninae) based on specimens from the species' presumed distribution range. We
      found two greatly differentiated groups, with 8.6% uncorrected sequence
      differences in the mtDNA cytochrome b gene; one group was distributed exclusively
      in the Yodo River system (excluding Lake Biwa and rivers flowing into the lake).
      This differentiation was supported by results from three nuclear DNA loci, and it
      was concluded that the Yodo population is an undescribed cryptic species. Based
      on mtDNA haplotype distribution and endemicity, B. zezera was determined to be
      indigenous to the Ise Bay area (Nobi Plain), Lake Biwa basin (excluding the Yodo
      River outlet and its tributaries), the Sanyo region, and northern Kyushu. The
      population in the Ise Bay area was the most differentiated from the others, while
      that in Kyushu was the second-most differentiated. It was confirmed that an
      endemic population closely related to the Lake Biwa population is naturally
      distributed in the Sanyo region.

PMID- 20695781
TI  - Biochemical and immunohistochemical analyses of a GnRH-like peptide in the neural
      ganglia of the Pacific abalone Haliotis discus hannai (Gastropoda).
AB  - We examined whether gonadotropin-releasing hormone (GnRH)-like peptides are
      present in the neural ganglia of the gastropod Pacific abalone (Haliotis discus
      hannai) by reverse-phase high performance liquid chromatography (rpHPLC) combined
      with time-resolved fluoroimmunoassay (TR-FIA) analysis and by
      immunohistochemistry. Cerebral ganglion extracts showed a similar retention time
      to lamprey GnRH-II (lGnRH-II) in rpHPLC combined with TR-FIA analysis. GnRH-like
      immunoreactive (ir) cell bodies (which reacted with a mouse monoclonal antibody
      raised against the common amino acid sequence of vertebrate GnRH) were detected
      in the peripheral region of the cerebral ganglion, and they were observed to send
      fibers into the neuropil. GnRH-like-ir fibers were also detected in the neuropil
      of the pedal ganglion, the visceral nerve, and the nerve originating from the
      pedal ganglion. Chicken GnRH-II (cGnRH-II)-like-ir fibers (which reacted with a
      rabbit polyclonal antibody raised against cGnRH-II) were also observed in the
      neuropil of the cerebral ganglion. GnRH-like-ir fibers and cGnRH-II-like-ir
      fibers were distinguishable in the neuropil of the cerebral ganglion by double
      staining immunohistochemistry. These results suggest that multiple GnRH-like
      peptides exist in the neural ganglia of the Pacific abalone.

PMID- 20695782
TI  - A comparative analysis of mitochondrial genomes in Orthoptera (Arthropoda:
      Insecta) and genome descriptions of three grasshopper species.
AB  - The complete sequences of mitochondrial DNA (mtDNA) from the three new
      grasshopper species, Euchorthippus fusigeniculatus, Mekongiana xiangchengensis
      and Mekongiella xizangensis, consisting of 15772 bp, 15567 bp, and 15885 bp,
      respectively, were analyzed and compared to mtDNAs from other 19 Orthoptera
      species obtained from GenBank. The three mitochondrial genomes contain a standard
      set of 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes. and
      an A+T-rich region in the same order as those of the other analyzed caeliferan
      species, but different from those of the ensiferan species by the rearrangement
      of trnD and trnK. The putative initiation codon for the cox1 gene is ATC in E.
      fusigeniculatus, CTG in M. xiangchengensis and CCG in M. xizangensis. All
      secondary structures of tRNA-Ser((AGN)) in the three species lack a DHU arm. In
      this study, we stressed the comparative analysis of the stem-loop secondary
      structure in A+T-rich region of all Orthoptera species available to date, and
      report new findings which may facilitate further investigation and better
      understanding of this secondary structure. Finally, we undertook a phylogenetic
      study of all Orthoptera species available from GenBank to date based on three
      different datasets using parsimony, maximum likelihood, and Bayesian inference.
      Our result showed that protein-coding genes (PCG) and amino acid sequences
      (PCG_PROT) provided good resolution of higher-level relationships within the
      Orthoptera, whereas ribosomal RNA genes (RIBO) perform poorly under different
      optimality criteria.

PMID- 20695783
TI  - Ontogeny and function of the fifth limb in Cypridocopain ostracods.
AB  - The exoskeleton of arthropods undergoes reformation at every molting.
      Accordingly, external morphology can metamorphose through molting. In some
      crustaceans, the function of appendages is modified through ontogeny. These
      morphological modifications require accordant modification of the correlation
      between different body parts because the morphological function depends on the
      combined correlation between different parts. In the case of crustacean
      morphology, exoskeleton and muscles are correlated to each other. The functional
      morphology of the fifth limb of cypridoid ostracods transforms from "walking leg
      + mouthparts (+ possibly respiratory parts)" to "mouthparts + respiratory parts +
      grasping hook (in males only)" through ontogeny. In this study, the three
      dimensional structures of the exoskeleton and muscular systems were observed by
      confocal laser-scanning microscopy in some species of suborder Cypridocopina. The
      muscular system is reportedly not changed by the ontogeny of appendages in
      females, but it does change in males. Furthermore, regional cell proliferation,
      which was detected previously, represented the causal factor of exoskeletal
      modification. I therefore conclude that the enlarged endite in the female fifth
      limb is produced by exoskeletal modification based on regional cell
      proliferation, rather than by a change in the muscular system. In contrast,
      modification in the male requires a change in the muscular system in addition to
      exoskeletal modification.

PMID- 20695784
TI  - A new species of the genus Tegastes (Copepoda: Harpacticoida: Tegastidae) from
      hydrothermal vents in the Okinawa Trough.
AB  - We describe a new species, Tegastes okinawaensis, from 583-711 meter-deep
      hydrothermal vents in the Okinawa Trough, Japan. This species is clearly
      distinguishable from its congeners by four combined characters, namely 1) the
      last three abdominal somites are depressed inwardly towards the body, 2) there is
      sexual dimorphism in the number of setae of P3 and P4, 3) the male antennule is 9
      segmented, with the 7th segment formed by incomplete fusion of two segments, and
      4) the caudal rami are small with a distorted quadrangular shape. Additionally,
      the species is easily distinguishable from its congeners by the distal endopodal
      segment of P4, which is armed with six setae - this character has never been
      reported in previous descriptions of congeners. This report is the first of a
      species in the genus Tegastes living at ocean depths of greater than 580 m in the
      northwestern Pacific.

PMID- 20695785
TI  - A new genus of endoparasitic copepods (Cyclopoida: Enterognathidae), forming a
      gall in the calyx of deep-sea crinoids.
AB  - A new genus and species of cyclopoid copepod belonging to the family
      Enterognathidae, Parenterognathus troglodytes, is described from a gall on the
      calyx of the deep-sea crinoid Glyptometra crassa (Clark, 1912) collected at
      depths of 775-787 m off Kumano-nada, middle Japan. The new genus can be
      distinguished from the three known genera of the family by body tagmosis and by
      the segmentation and armature of the appendages. This is the first record of this
      family from the Pacific Ocean. This family seems to be host-specific to
      relatively basal deuterostomes, such as echinoderms and hemichordates. The
      evolutionary transformation and history of the Enterognathidae are briefly
      discussed.

PMID- 20695786
TI  - A review of Roquettea, with description of three new Brazilian species and notes
      on Gryne (Opiliones, Cosmetidae, Discosomaticinae).
AB  - The genua Roquettea Mello-Leitao, hitherto monotypic and known from Brazilian
      state of Para, is rediagnosed, the type species, Roquettea singularis is
      redescribed, including a report on two male morphs, being the second record of
      male polymorphism in Cosmetidae, the first in South America. Three new species
      are described from northern Brazil - Roquettea taurine n. sp. (which possesses a
      unique horned ocularium) and Roquettea jalapensis n. sp. (without notable scutal
      structures), both from the state of Tocantins, being the first record of the
      family Cosmetidae from Tocantins; and Roquettea scrotalis n. sp. (with a unique 2
      balled dorsal tuberous complex) from Amapa state, being the first record of the
      subfamily Discosomaticinae from Amapa. Roquettea is compared to the closely
      related genus Gryne, both currently placed in Discosomaticinae, and also to
      Profus, the type genus of the subfamily. The unity of Discosomaticinae is
      discussed, and evidence for the monophyly of this subfamily is weak at best. Male
      genitalia are for the first time illustrated and described for genera Protus,
      Roquettea and Gryne, and SEM micrographs are used for the first time in
      descriptions of Cosmetidae.

PMID- 20695787
TI  - Nucleotide sequences and chromosomal localization of 45S and 5S rDNA in
      Neolissochilus hexagonolepis (Pisces, Cyprinidae), using dual-color fish.
AB  - Dual-color fluorescence in situ hybridization (FISH) was performed to study the
      simultaneous localization of major (45S) and minor (5S) family ribosomal RNA
      genes on chromosomes of Neolissochilus hexagonolepis. The partial 45S (18S, ITS
      1, 5.8S, ITS 2 and 28S) and complete 5S (coding and NTS) rDNA units were
      amplified, sequenced, analyzed, and mapped on the metaphase chromosomes. The
      complete 18S, 5.8S and partial 28S rDNAs were 1849 bp, 157 bp and 1819 bp long,
      respectively. Internal transcribed spacers, namely ITS 1 (828 bp) and ITS 2 (359
      bp), showed significant nucleotide variations from other fish species listed in
      NCBI database. The 5S rDNA contained an identical coding region of 120 bp and a
      highly divergent, non-transcribed 81-bp spacer. The specimens of N. hexagonolepis
      showed six bright fluorescent signals of 18S, while the 5S signals were present
      only on one pair of chromosomes. Subsequent analyses between conventional Ag-NORs
      and 18S rDNA FISH strongly suggested the possible inactivation of one pair of
      NORs that was localized at a telomeric position of a submetacentric chromosome.
      The sequencing and chromosomal localization of 45S and 5S rDNAs may serve as a
      useful genetic marker in taxonomic classification as well as in phylogenetic and
      evolutionary studies.

PMID- 20695788
TI  - Chronic spinal cord injury pain: pharmacological and non-pharmacological
      treatments and treatment effectiveness.
AB  - PURPOSE: To describe pharmacological and non-pharmacological pain treatments used
      for chronic spinal cord injury pain (CSCIP) and current treatment effectiveness
      in a large Dutch population with a spinal cord injury (SCI). METHOD: Postal
      survey among 575 persons with SCI. The main outcome measures were the pain
      intensity score of the Chronic Pain Grade questionnaire, past and current pain
      treatments, and perceived effectiveness of current pain treatments. RESULTS:
      Response rate was 49% (279 persons) and 215 respondents (77.1%) had CSCIP. Most
      respondents with CSCIP (62.8%) reported more than one pain type, of which
      neuropathic pain was most frequently reported (69.3%). Of this group with CSCIP,
      63.8% was currently involved in some kind of treatment, but nevertheless high
      levels of pain (mean 52.8 on a 0-100 scale) were reported. Massage
      (therapy)/relaxation (training), anticonvulsants, and non-steroidal anti
      inflammatory drugs (NSAIDs) were the most often used treatments. The current
      treatments that were most often perceived as effective were
      acupuncture/magnetising, cannabis/alcohol, physiotherapy and exercise, and
      massage (therapy)/relaxation (training). TENS/ultrasound and antidepressants were
      least often perceived as effective. CONCLUSIONS: Many SCI pain treatments have
      been tried. Acupuncture/magnetising, cannabis/alcohol, and physiotherapy and
      exercise were considered most effective. Further research is needed to establish
      effective SCI pain treatments.

PMID- 20695789
TI  - Chimeric vessel tissue engineering driven by endothelialized modules in
      immunosuppressed Sprague-Dawley rats.
AB  - Modular tissue engineering is a means of building functional, vascularized
      tissues using small (~1 mm long*0.5 mm diameter) components. While this approach
      is being explored for its utility in adipose and cardiac tissue engineering and
      in islet transplantation, the initial question in this study was to assess the
      fate of the endothelial cells (EC) after transplantation delivered on the surface
      of modules, without an embedded cell. Rat aortic EC-covered collagen gel modules
      were transplanted into the omental pouch of allogeneic (outbred) Sprague-Dawley
      rats with and without immunosuppressive drug treatment (atorvastatin and
      tacrolimus) for 3-60 days. There was a significant increase in vessel density at
      all time points in the drug treated rats as compared to untreated rats. Green
      fluorescent protein (GFP)-positive donor rat aortic EC migrated from the surface
      of the modules and formed primitive vessels by day 7. In the untreated rats, the
      GFP-positive cells were not seen after day 7. In drug-treated rats, GFP-positive
      vessels matured over time, accumulated erythrocytes, were supported by host
      smooth muscle cells, and formed chimeric vessels that survived until day 60. This
      resulted in the formation of a densely vascularized, perfusable network by day
      60. To our knowledge, this is the first study that demonstrates that primary
      unmodified EC, without the addition of supporting cells, form a chimeric and
      stable vascular bed in allogeneic, although drug-treated, animals.

PMID- 20695790
TI  - A power balance model for handcycling.
AB  - PURPOSE: To demonstrate the applicability of the power balance model to elite
      handcycling and to obtain values for gross efficiency (GE). METHODS: Four members
      of the Dutch Paralympic team performed trials on a 250-m indoor track. Velocity
      (v) and power output (PO) were measured in conjunction with physiological
      measures to obtain values for GE. The data were used to construct and validate a
      power balance model of handcycling. RESULTS: The empirically derived relationship
      between PO and velocity was: PO = 0.20v3 + 2.90v (R2= 0.95). Mean GE during
      submaximal performance was 17.9%  +/- 1.6%. CONCLUSION: Handcycling performance
      can successfully be modelled with a power balance model. The model provides
      insight into the magnitude of power production and dissipation during elite
      handcycling. Handcycling is a relatively efficient upper body mode of propulsion
      with associated high metabolic demand at race velocities.

PMID- 20695791
TI  - Understanding the causal factors of obesity using the International
      Classification of Functioning, Disability and Health.
AB  - PURPOSE: Behavioural, personal, psychological, sociodemographic, environmental,
      biological and childbearing factors have been associated with obesity among
      women. This study quantitatively explored the effects of these factors on
      predicting body mass index (BMI) in U.S. women using the International
      Classification of Functioning, Disability and Health (ICF) and determined the
      effectiveness of using the ICF with population-level data. METHODS: We used the
      ICF Core Sets for Obesity, and data from the 1999-2006 National Health and
      Nutrition Examination Survey (NHANES) in a sample of 8766 U.S. women to quantify
      the impact of all associated causal factors. Linear regression was used in the
      analyses. RESULTS: Body image perceptions (42%) was the most significant
      contributor, followed by hypertension (12%), general health condition (11%),
      diabetes/borderline diabetes (10%), arthritis (9%) and performing vigorous
      activity (9%). CONCLUSIONS: To decrease obesity prevalence rates in U.S. women,
      obesity prevention and treatment programmes should parallel the contributory
      effects of its most significant causal factors of psychological, biological and
      behavioural. In addition, more research and data are needed to explore the
      relationship between BMI in women and the multiple influencing factors by going
      beyond the more frequently available information of age, gender, race, education,
      income and parity.

PMID- 20695793
TI  - Using the ICF-CY to organise characteristics of children's functioning.
AB  - PURPOSE: Researchers in early childhood conducting secondary data analysis face a
      number of challenges shared by other early childhood professionals, including
      needs for efficient, descriptive language to convey characteristics of
      individuals' functioning to varied audiences. These professionals may benefit
      from a systematic approach for organising and sharing data which can describe
      children as functioning wholes with skills across many domains. This study
      explored the ability of the International Classification of Functioning,
      Disability and Health for Children and Youth (ICF-CY) to address these needs by
      considering its utility to adequately organise and describe constructs of child
      functioning in an existing data set. METHODS: Variables from a large data set
      were mapped to chapters of the ICF-CY Activities/Participation component. Factor
      analysis with a split-half approach was utilised to explore the relative
      structural integrity of chapter structure as a mechanism for generating a profile
      of constructs of child functioning. RESULTS: All variables mapped to chapters of
      the ICF-CY Activities/Participation component. The factor analyses indicated that
      variables, which mapped to the same chapter tended to load to the same factor,
      with the exception of items describing child communication which loaded to all
      factors. Results further suggested the overlapping nature of children's skills,
      such that skills in one area likely impact functioning in other functioning
      domains. CONCLUSION: The ICF-CY provides adequate depth and breadth for use in
      conceptualising new questions and information in existing data sets. Findings
      suggest the structure of the ICF-CY Activities/Participation chapters could be
      used for generating meaningful profiles of human functioning across salient
      domains.

PMID- 20695792
TI  - De novo myocardial regeneration: advances and pitfalls.
AB  - The capability of adult tissue-derived stem cells for cardiogenesis has been
      extensively studied in experimental animals and clinical studies for treatment of
      postischemic cardiomyopathy. The less-than-anticipated improvement in the heart
      function in most clinical studies with skeletal myoblasts and bone marrow cells
      has warranted a search for alternative sources of stem cells. Despite their
      multilineage differentiation potential, ethical issues, teratogenicity, and
      tissue rejection are main obstacles in developing clinically feasible methods for
      embryonic stem cell transplantation into patients. A decade-long research on
      embryonic stem cells has paved the way for discovery of alternative approaches
      for generating pluripotent stem cells. Genetic manipulation of somatic cells for
      pluripotency genes reprograms the cells to pluripotent status. Efforts are
      currently focused to make reprogramming protocols safer for clinical applications
      of the reprogrammed cells. We summarize the advancements and complicating
      features of stem cell therapy and discuss the decade-and-a-half-long efforts made
      by stem cell researchers for moving the field from bench to the bedside as an
      adjunct therapy or as an alternative to the contemporary therapeutic modalities
      for routine clinical application. The review also provides a special focus on the
      advancements made in the field of somatic cell reprogramming.

PMID- 20695794
TI  - Efficacy of cognitive behavioural therapy for children and adolescents with
      traumatic brain injury.
AB  - PURPOSE: Behavioural and psychological disorders after traumatic brain injury
      (TBI) are very common. The purposes of this study were to estimate the frequency
      of these problems in our sample, to evaluate the effectiveness of cognitive
      behavioural therapy (CBT) and to assess the predictive value of important
      clinical variables for the treatment outcome. METHOD: Forty patients aged 4-18
      years were included in this study. Twenty-eight patients received CBT at our
      Institute (clinical group), while 12 patients did not receive any treatment at
      all (control group). The CBCL/4-18 and the VABS were administered to parents at
      the beginning of the study and after 12 months. RESULTS: A high frequency of
      psychological and behavioural problems was found in both groups of patients.
      After CBT, the clinical group showed a significant advantage on several CBCL
      scales and a greater increase in adaptive behaviour on the VABS Socialisation
      domain. The Glasgow Coma Scale score, days of unconsciousness and age at injury
      were not predictors of the severity of psychological problems at the follow-up
      for the patients of the clinical group. CONCLUSIONS: Our results suggest that CBT
      is an effective intervention for young patients with psychological problems after
      TBI.

PMID- 20695795
TI  - Hidden danger: the raw facts about hepatitis E virus.

PMID- 20695796
TI  - Pig liver sausage as a source of hepatitis E virus transmission to humans.
AB  - BACKGROUND: The source and route of autochthonous hepatitis E virus (HEV)
      infections are not clearly established in industrialized countries despite
      evidence that it is a zoonosis in pigs. We investigated the role of figatellu, a
      traditional pig liver sausage widely eaten in France and commonly consumed raw,
      as a source of HEV infection. METHODS: A case-control study was conducted of 3
      patients who presented autochthonous hepatitis E and 15 members of their 3
      different families. Anti-HEV immunoglobulin G and immunoglobulin M antibody
      testing was performed with commercial assays. HEV RNA was detected in serum
      samples of patients and in pig liver sausages by means of real-time polymerase
      chain reaction and sequenced by means of in-house sequencing assays. Genetic
      links between HEV sequences were analyzed. RESULTS: Acute or recent HEV
      infection, defined by detection of anti-HEV immunoglobulin M antibodies and/or
      HEV RNA, was observed in 7 of 13 individuals who ate raw figatellu and 0 of 5
      individuals who did not eat raw figatellu (P=.041). Moreover, HEV RNA of genotype
      3 was recovered from 7 of 12 figatelli purchased in supermarkets, and
      statistically significant genetic links were found between these sequences and
      those recovered from patients who ate raw figatellu. CONCLUSION: Our findings
      strongly support the hypothesis of HEV infection through ingestion of raw
      figatellu.

PMID- 20695797
TI  - Intestinal antimicrobial gene expression: impact of micronutrients in
      malnourished adults during a randomized trial.
AB  - BACKGROUND: Because both micronutrients and antimicrobial peptides protect
      against diarrhea, we looked for an effect on intestinal antimicrobial peptide
      gene expression during a randomized controlled trial of multiple micronutrient
      (MM) supplementation. METHODS: Consenting adults (n=287) in Lusaka, Zambia, were
      randomized to receive a daily MM supplement or placebo and were followed up for
      3.3 years, with a crossover after 2 years. Intestinal biopsy samples were
      obtained at annual intervals, and messenger RNA of the intestinal antimicrobial
      peptides human alpha defensin (HD) 5, HD6, human beta-defensin (hBD) 1, hBD2, and
      LL-37 were quantified by real-time reverse-transcriptase polymerase chain
      reaction. Samples were also obtained during diarrhea episodes and after
      convalescence. RESULTS: There was no effect overall of treatment allocation.
      However, in malnourished adults (body mass index < or =18.5), HD5 mRNA was
      increased by 0.8 log transcripts/microg total RNA in MM recipients, compared with
      HD5 mRNA in placebo recipients (P=.007). During diarrhea, HD5 expression was
      reduced by 0.8 log transcripts in placebo recipients (P=.02) but was not reduced
      in MM recipients, nor was it reduced after the crossover. Correlations between
      HD5 and nutritional status were found that were sex-specific but not explained by
      serum leptin or adiponectin concentrations. CONCLUSIONS: Micronutrient
      supplementation was associated with up-regulation of HD5 only in malnourished
      adults. Interactions between antimicrobial gene expression and nutritional status
      may help to explain the increased risk of infection in individuals with
      malnutrition.

PMID- 20695798
TI  - Characteristics of autochthonous hepatitis E virus infection in solid-organ
      transplant recipients in France.
AB  - BACKGROUND: Hepatitis E virus (HEV) infections can lead to chronic hepatitis in
      immunocompromised patients. We have investigated the risk factors for HEV
      infection among solid-organ transplant recipients and the characteristics of
      these infections. METHODS: We performed serological tests, quantified the virus,
      and genotyped the virus in plasma samples. We performed a case-control study with
      HEV-infected patients and control participants matched for sex and age who were
      recruited from a population of solid-organ transplant recipients with no markers
      of HEV infection. RESULTS: We investigated 38 consecutive cases of HEV genotype 3
      infection. Twenty-two (58%) of these 38 patients developed a chronic infection.
      The acute-phase aminotransferase levels were higher in the patients who cleared
      the virus than in those who developed chronic infections. The anti-HEV
      immunoglobulin G and immunoglobulin M profiles and HEV RNA concentration in
      patients who cleared the virus were similar to those in patients who developed a
      chronic infection. A logistic regression analysis of 37 case patients and 148
      control participants indicated that the only factor independently associated with
      HEV infection was the consumption of game meat (68% of case patients vs 47% of
      control participants; odds ratio, 2.32; 95% confidence interval, 1.04-5.15).
      CONCLUSION: Immunocompromised patients should avoid eating insufficiently cooked
      game meat or pork products so as to reduce the risk of HEV infection and chronic
      liver disease.

PMID- 20695799
TI  - Multicenter study of Clostridium difficile infection rates from 2000 to 2006.
AB  - OBJECTIVE: To compare incidence rates of Clostridium difficile infection (CDI)
      during a 6-year period among 5 geographically diverse academic medical centers
      across the United States by use of recommended standardized surveillance
      definitions of CDI that incorporate recent information on healthcare facility
      (HCF) exposure. METHODS: Data on C. difficile toxin assay results and dates of
      hospital admission and discharge were collected from electronic databases. Chart
      review was performed for patients with a positive C. difficile toxin assay result
      who were identified within 48 hours after hospital admission to determine whether
      they had any HCF exposure during the 90 days prior to their hospital admission.
      CDI cases, defined as any inpatient with a stool toxin assay positive for C.
      difficile, were categorized into 5 surveillance definitions based on recent HCF
      exposure. Annual CDI rates were calculated and evaluated by use of the chi(2)
      test for trend and the chi(2) summary test. RESULTS: During the study period,
      there were significant increases in the overall incidence rates of HCF-onset, HCF
      associated CDI (from 7.0 to 8.5 cases per 10,000 patient-days; P < .001);
      community-onset, HCF-associated CDI attributed to a study hospital (from 1.1 to
      1.3 cases per 10,000 patient-days; P = .003); and community-onset, HCF-associated
      CDI not attributed to a study hospital (from 0.8 to 1.5 cases per 1,000
      admissions overall; P < .001). For each surveillance definition of CDI, there
      were significant differences in the total incidence rate between HCFs.
      CONCLUSIONS: The increasing incidence rates of CDI over time and across
      healthcare institutions and the correlation of CDI incidence in different
      surveillance categories suggest that CDI may be a regional problem and not
      isolated to a single HCF within a community.

PMID- 20695800
TI  - Uncompensated medical provider costs associated with prior authorization for
      prescription medications in an HIV clinic.
AB  - Although prior authorization (PA) for prescription medications is widely employed
      for cost-containment for third-party insurers, it is a frustrating aspect of
      outpatient clinical care that imposes uncompensated costs to medical providers.
      To characterize these costs, we monitored the PA-associated administrative and
      operational process at the University of Alabama at Birmingham 1917 HIV Clinic
      over a 2-year period. A total of 288 PAs were processed with a mean (+/- standard
      deviation [SD]) of 3.1+/-5.8 days delay in the patient's access to medication. A
      mean (+/-SD) of 26.8+/-18.4 min was spent by the nurse practitioner and 6.5+/-2.9
      min was spent by a clerk per PA. Nearly three-quarters (73%) of PAs were
      approved, 18% were denied, and 10% were voided. The mean (+/-SD) pages of
      paperwork was 5.8+/-6.5. The overall cost was $41.60 per PA. Although evidence
      supports that PA reduces third-party expenditures, it significantly delays
      medication accessibility for patients and imposes high costs that negatively
      impact operating margins for health care providers.

PMID- 20695801
TI  - Integrated analysis of CANVAS 1 and 2: phase 3, multicenter, randomized, double
      blind studies to evaluate the safety and efficacy of ceftaroline versus
      vancomycin plus aztreonam in complicated skin and skin-structure infection.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause
      of complicated skin and skin-structure infection (cSSSI). Increasing
      antimicrobial resistance in cSSSI has led to a need for new safe and effective
      therapies. Ceftaroline was evaluated as treatment for cSSSI in 2 identical phase
      3 clinical trials, the pooled analysis of which is presented here. The primary
      objective of each trial was to determine the noninferiority of the clinical cure
      rate achieved with ceftaroline monotherapy, compared with that achieved with
      vancomycin plus aztreonam combination therapy, in the clinically evaluable (CE)
      and modified intent-to-treat (MITT) patient populations. METHODS: Adult patients
      with cSSSI requiring intravenous therapy received ceftaroline (600 mg every 12 h)
      or vancomycin plus aztreonam (1 g each every 12 h) for 5-14 days. RESULTS: Of
      1378 patients enrolled in both trials, 693 received ceftaroline and 685 received
      vancomycin plus aztreonam. Baseline characteristics of the treatment groups were
      comparable. Clinical cure rates were similar for ceftaroline and vancomycin plus
      aztreonam in the CE (91.6% vs 92.7%) and MITT (85.9% vs 85.5%) populations,
      respectively, as well as in patients infected with MRSA (93.4% vs 94.3%). The
      rates of adverse events, discontinuations because of an adverse event, serious
      adverse events, and death also were similar between treatment groups.
      CONCLUSIONS: Ceftaroline achieved high clinical cure rates, was efficacious
      against cSSSI caused by MRSA and other common cSSSI pathogens, and was well
      tolerated, with a safety profile consistent with the cephalosporin class.
      Ceftaroline has the potential to provide a monotherapy alternative for the
      treatment of cSSSI. TRIAL REGISTRATION: ClinicalTrials.gov identifiers:
      NCT00424190 for CANVAS 1 and NCT00423657 for CANVAS 2.

PMID- 20695802
TI  - Estimating the prevalence of personality disorders in the community.
AB  - A series of recent epidemiological studies has assessed the prevalence of
      personality disorders in the general population. However, all these reports run a
      serious risk of overestimation. First, all research is based on problematic
      definitions in DSM-IV-TR, both for overall PD and for specific categories.
      Second, all studies suffer from a failure to distinguish problematic traits from
      clinical disorders. Third, many methods of assessment have been inadequate to
      make diagnostic decisions requiring subtlety and clinical experience.
      Overestimation of prevalence negatively affects research, which would benefit
      from a narrower definition of PDs based on dysfunction in multiple domains.

PMID- 20695803
TI  - Revised NESARC personality disorder diagnoses: gender, prevalence, and
      comorbidity with substance dependence disorders.
AB  - We applied different diagnostic rules for diagnosing personality disorders to the
      NESARC epidemiological study of over 40,000 individuals. Specifically, unlike
      previous NESARC publications, we required that each personality disorder
      criterion be associated with significant distress or impairment in order to be
      counted toward a personality disorder (PD) diagnosis. Results demonstrated
      significant reductions in prevalence rates for PDs (9.1% versus 21.5% using
      original NESARC algorithms), and these revised prevalence rates were much more
      consistent with recent epidemiological studies in the U.S. and Great Britain. We
      also found gender differences in the prevalence rate for most PDs. Comorbidity
      analyses revealed strong associations between PDs and alcohol dependence, drug
      dependence, and tobacco dependence. PD diagnoses were also associated with scores
      on dysfunction and impairment, perceived stress and less social support, lifetime
      history of suicide attempts, interpersonal difficulties, and problems with legal
      authorities.

PMID- 20695804
TI  - Genetic covariance structure of the four main features of borderline personality
      disorder.
AB  - The patient population of borderline personality disorder (BPD) is heterogeneous;
      many different combinations of BPD symptoms can lead to a BPD diagnosis. We
      investigated to what extent the covariance among four main components of BPD is
      explained by shared genetic and environmental factors. Using an extended twin
      design, multivariate genetic models were applied to the scales of the PAI-BOR, a
      self-report questionnaire tapping four main features of BPD (affective
      instability, identity problems, negative relationships, and self-harm). Data on
      the four BPD scales were available for 5,533 twins and 1,202 siblings from the
      Netherlands, Belgium, and Australia. The correlations among the scales ranged
      from 0.23 to 0.50 and were best explained by a genetic common pathway model. This
      model specifies that genes and environment influence the covariance between four
      main features of BPD in qualitatively similar ways, through a single latent
      factor representing the BPD construct. The heritability of the latent BPD factor
      was 51% and the remainder of its variance was explained by unique environmental
      influences. For each BPD scale, except self-harm, around 50% of its variance was
      explained by the latent BPD factor. The remaining variance for each of the four
      scales was explained by genetic (4% for affective instability to 20% for self
      harm) and environmental (38% for negative relationships to 67% for self-harm)
      factors that were specific to each scale.

PMID- 20695805
TI  - Decoding of facial expression of emotion in criminal psychopaths.
AB  - To examine whether psychopaths exhibit specific deficits in nonverbal emotional
      processing, 20 criminal psychopaths, 23 criminal nonpsychopaths, both groups
      identified with Hare's (2003) Psychopathy Checklist-Revised, and 25 noncriminals
      completed the facial affect recognition test developed by Philippot et al.
      (1999). All participants were males. The criminal psychopaths and nonpsychopaths
      were confined in a high-security prison. Forty slides were presented on a
      computer screen, each representing a male or a female actor portraying facial
      expressions of happiness, anger, sadness, fear, or disgust. Facial stimuli varied
      in emotional intensity (0%, 30%, 70%, and 100%). Overall, both criminal groups
      were less accurate than controls in decoding facial expression of emotion.
      Analysis of covariance showed that this effect is accounted for by differences in
      level of education of the participants. While criminal nonpsychopaths did not
      differ from criminal psychopaths in term of overall accuracy, they were less
      accurate for amygdalian emotion than for nonamygdalian ones. Criminal
      psychopaths' performance, however, was not affected by the amygdalian nature of
      the facial display. This pattern of results is opposed to the Blair's amygdalian
      hypothesis.

PMID- 20695806
TI  - Stability of borderline personality disorder features in girls.
AB  - Little empirical evidence exists regarding developmental antecedents of
      borderline personality disorder (BPD) features in children and adolescents. As a
      first step in addressing this gap in our knowledge, this study examined the
      factor structure and stability of putative underlying BPD features, specifically
      impulsivity, negative affectivity, and interpersonal aggression, in 6-12-year-old
      girls. We report on results from exploratory and confirmatory factor analyses of
      underlying BPD dimensions as rated by parents and teachers over six successive
      data waves in a large, community sample of girls (N = 2,451). Six factors were
      derived from parent ratings (i.e., Cognitive Dyscontrol, (Lack of) Self-Control,
      Hostility, Depression/Anxiety, Hyperactivity, and Relational Aggression) and five
      factors were derived from teacher reports (i.e., Cognitive Dyscontrol,
      Hyperactivity, (Lack of) Self-Control, Relational Aggression, and Depression).
      The item composition of similar parent and teacher factors was highly consistent.
      The year-to-year stability from ages 6 to 12 was high for parent factor scores (r
      ranging from .71-.85) and moderately high for teacher factor scores (r ranging
      from .49-.77). These findings suggest that underlying dimensions of BPD features
      can be reliably measured and are stable in 6-12-year-old girls.

PMID- 20695807
TI  - Psychopathic personality traits in middle-aged male twins: a behavior genetic
      investigation.
AB  - Psychopathic personality is characterized by interpersonal dominance,
      impulsivity, sensation seeking, poor planning, and aggressiveness. Studies have
      shown that the Multidimensional Personality Questionnaire (MPQ) can be used to
      estimate scores on the fearless-dominant (FD) and the impulsive-antisocial (IA)
      dimensions of the Psychopathic Personality Inventory (PPI), the best validated
      self-report measure of psychopathic personality traits. Prior behavior genetic
      studies reported roughly equal genetic and nonshared environmental influences for
      both FD and IA, which remained stable from adolescence to young adulthood.
      However, no prior studies address genetic and environmental influences on these
      dimensions beyond early adulthood. We utilized the classic twin method to examine
      genetic and environmental influences on variance in FD and IA in a sample of
      middle-aged male twins. Biometric modeling indicated that the variance in both
      factors is best explained by additive genetic and nonshared environmental
      influences. FD showed roughly equal contributions from genetic and environmental
      factors, whereas IA showed greater contributions from environmental than genetic
      factors. Additionally, the small phenotypic correlation between FD and IA was
      explained entirely by nonshared environmental factors.

PMID- 20695808
TI  - "Let's get down to business: a validation study of the Psychopathic Personality
      Inventory among a sample of MBA students.".
AB  - While the Psychopathic Personality Inventory (PPI) has gained increasing
      attention as a measure of noncriminal psychopathy, absent has been research
      involving samples including business people. This study investigated the validity
      of the PPI with such a population by examining the association between
      psychopathic traits and moral decision-making among MBA students. Sixty-six MBA
      students were assessed using the PPI, the MACH-IV (a measure of
      Machiavellianism), the Ethical Position Questionnaire (EPQ), and the Defining
      Issues Test (DIT-2). Only PPI Machiavellian Egocentricity was associated with
      level of post-conventional moral reasoning. MACH-IV Machiavellianism was a
      stronger predictor of the Subjectivist ethical position than were PPI subscales.
      However, a combination of MACH-IV Machiavellianism and four PPI scales accounted
      for 46% of the variance in Subjectivism. Results suggested that Machiavellian
      Egocentricity and Machiavellianism are distinct constructs. Benning, Patrick,
      Hicks, Blonigen, & Krueger (2003)'s two factor model of the PPI was also
      supported. In general, the findings provided further validation for the PPI as a
      tool for assessing psychopathic traits among "mainstream" individuals, including
      business people.

PMID- 20695809
TI  - Validity of the Spanish version of the Inventory of Interpersonal Problems and
      its use for screening personality disorders in clinical practice.
AB  - We studied the reliability and validity of two versions (64 items and 32 items)
      of the Spanish translation of the Inventory of Interpersonal Problems (IIP-64 and
      IIP-32) and their usefulness as screening instruments for personality disorders
      in a sample of 190 outpatients and 66 healthy subjects. Patients were assessed
      using the IIP-64 and IIP-32, the Structured Clinical Interview for DSM-IV Axis II
      Personality Disorder diagnoses, and the Global Assessment of Functioning. The
      internal consistency and test-retest reliability were satisfactory. As
      theoretically predicted, factor analysis produced eight factors, and
      multidimensional scaling indicated the two dimensions of affiliation and
      dominance. Finally, a cutoff point of 87 for the IIP-64 showed 87% sensitivity
      and 85% specificity, whereas a cutoff point of 44 for the IIP-32 showed 82%
      sensitivity and 75% specificity. The Spanish versions of the IIP-32 and the IIP
      64 are valid instruments for assessing interpersonal problems and for screening
      personality disorders in clinical practice.

PMID- 20695810
TI  - Toward a more psychometrically sound brief measure of schizotypal traits:
      introducing the SPQ-Brief Revised.
AB  - Psychometric case identification of individuals at risk for developing
      schizophrenia-spectrum disorders is an important enterprise. Unfortunately,
      current instruments for this purpose are limited. The present studies sought to
      improve the Schizotypal Personality Questionnaire-Brief (SPQ-Brief), a measure of
      schizotypal traits that has come under recent criticism. In the first study, we
      conducted exploratory factor analysis on the SPQ-Brief using a Likert-style
      scoring format in a large sample of nonclinical adults. Although acceptable
      internal consistency was found, the original factor structure was not supported.
      In the second study, we administered the full version of the SPQ to a separate
      large nonclinical adult sample and employed exploratory and confirmatory factor
      analysis to identify critical items that could be used to revise the SPQ-Brief.
      The end product of these studies is the SPQ-Brief Revised, which offers a
      subordinate seven-factor and super-ordinate three or four factor solution,
      employs a Likert-scale format to improve sensitivity, and is brief (34 items).

PMID- 20695811
TI  - Long-term patterns of immune investment by wild deer mice infected with Sin
      Nombre virus.
AB  - Immunocompetence of animals fluctuates seasonally, However, there is little
      consensus on the cause of these fluctuations. Some studies have suggested that
      these patterns are influenced by changes in reproductive condition, whereas
      others have suggested that differences result from seasonal variations in energy
      expenditures. The objective of our study was to examine these contrasting views
      of immunity by evaluating seasonal patterns of immune response and reproduction
      in wild populations of deer mice Peromyscus maniculatus exposed to Sin Nombre
      virus (SNV). Over three consecutive fall (September, October, November) and three
      consecutive spring (March, April, May) sampling periods, we used titration enzyme
      linked immunosorbent assay (ELISA) to quantify virus-specific antibody production
      in 48 deer mice infected with SNV. Levels of reproductive hormones were
      quantified using ELISA. SNV antibody titers reached their lowest level during
      November (geometric mean titer [GMT] = 420) and their highest levels during
      September (GMT = 5,545) and May (GMT = 3,582), suggesting that the immune
      response of deer mice to SNV has seasonal patterns. The seeming decrease in
      antibody titer over winter coupled with the consistency in body masses suggests
      that during winter, immunocompetence may be compromised to offset the energetic
      costs of maintenance functions, including those associated with maintaining body
      mass. Deer mice showed distinct sex-based differences in SNV antibody production,
      with males producing higher antibody titers (GMT = 3,333) than females (GMT =
      1,477). Levels of reproductive hormones do not appear to influence antibody
      production in either males or females, as there was no correlation between
      estradiol concentrations and SNV antibody titer in female deer mice (r2 = 0.26),
      nor was there a significant relationship between levels of testosterone and SNV
      antibody titers in males (r2 = 0.28). Collectively, this study demonstrates that
      immunocompetence of wild deer mice is seasonally variable; however, reproduction
      is not the primary stressor responsible for this variation. Rather, the data
      suggest that deer mice may compromise immunocompetence during winter to offset
      other maintenance costs during this period.

PMID- 20695812
TI  - Metabolic rate variation over adult lifetime in the butterfly Vanessa cardui
      (Nymphalidae: Nymphalinae): aging, feeding, and repeatability.
AB  - Questions about the adaptive importance of metabolic rate can be approached only
      when measurements of differences between individuals are repeatable. We made
      daily measurements of CO(2) production, body mass, and food uptake over the adult
      life span of unmated Vanessa cardui kept under constant environmental conditions
      in both fed and unfed treatments. Mass and CO(2) production generally declined
      with age in both treatments, though with much day-to-day variability in the fed
      treatment. For the full samples, metabolic rate was repeatable for the unfed
      treatment (repeatability r = 0.60) but not for the fed treatment (r = 0.03).
      Differences between fed and unfed individuals of the same age range were
      repeatable for the unfed treatment (r = 0.39) but not for the fed treatment (r = 
      0.20). Removing age effects on CO(2) production yielded still higher
      repeatability in the unfed treatment (r = 0.83), though not in fed butterflies of
      the same age range (r = -0.02). However, repeatability of CO(2) production of fed
      butterflies increased sharply with age, rising to 0.82 for butterflies age 8-10
      d. Although food uptake mass was repeatable (r = 0.52), feeding history explained
      little variation in CO(2) production. We conclude that for V. cardui and possibly
      for other insects of similar feeding habit, variation in metabolic rate between
      individuals is best represented by measurements of unfed individuals of the same
      age or of older fed individuals.

PMID- 20695814
TI  - Masson's vegetant hemangioendothelioma arising in the uterine cervix during
      pregnancy: a case report.
AB  - BACKGROUND: Hemangioendothelioma is a rare benign intravascular tumor that can be
      confused with other vascular neoplasms. We report the first case of cervical
      vegetant intravascular hemangioendothelioma (Masson's tumor) arising in a
      pregnant woman. CASE REPORT: A 40-year-old woman at 15 weeks' gestation developed
      a voluminous cervical mass and vaginal bleeding. We excised the lesion during
      pregnancy because of its rapid growth, bleeding, and severe pain. The
      pathological diagnosis was Masson's tumor or intravascular papillary endothelial
      hyperplasia. The tumor showed strong estrogen and progesterone receptor
      expression.The patient underwent an elective cesarean section at term, giving
      birth to a healthy baby. Clinical follow-up at 3 years showed no complications or
      recurrence. CONCLUSIONS: Obstetricians should be aware that Masson's tumor may
      occasionally arise in the uterine cervix during pregnancy. This benign vascular
      tumor may display a rapid growth because of the presence of sex steroid
      receptors. Differential diagnosis should consider a malignant vascular tumor,
      including Kaposi's sarcoma and angiosarcoma. Surgical removal should not be
      postponed because of pain and bleeding. Fetal and maternal outcomes were
      favorable.

PMID- 20695815
TI  - Gender disparities in health and healthcare use among older adults.
AB  - BACKGROUND: Gender differences in health and the use of health services are a
      long-standing concern for the U.S. medical system. Our purpose was to examine if
      there are patterns of gender differences in the type of medical service used
      among older Americans. METHODS: We conducted a prospective study of 9164
      Americans aged >or=65 followed through the Health and Retirement Study (HRS), a
      national probability sample of community dwelling adults. Self-reported medical
      utilization between 2002 and 2004 was modeled as a function of 2002 baseline
      characteristics of the sample. RESULTS: Health needs were substantially greater
      among older women compared with men, but women had fewer economic resources.
      Controlling for health needs did little to explain gender differences in
      preventive care and increased gender differences in the use of hospital services.
      Women were less likely to have hospital stays (adjusted odds ratio [OR] = 0.79)
      and had fewer physician visits (3.07 vs. 3.30 median visits within 2 years) than
      men with similar demographic and health profiles. In contrast, the greater use of
      home healthcare among women was almost entirely explained by their greater health
      needs. CONCLUSIONS: These national data show that simple evaluations of age
      adjusted gender differences in the use of hospital and physician services that do
      not account for underlying health needs are in danger of understating these
      disparities.

PMID- 20695816
TI  - Facilitators and barriers to engagement in physical activity for people with
      multiple sclerosis: a qualitative investigation.
AB  - PURPOSE: To explore the barriers and facilitators to engagement in physical
      activity from the perspective of people with multiple sclerosis (MS). METHOD:
      This study adopted a qualitative descriptive design, using semi-structured
      interviews. Participants were recruited through local MS Societies and one
      District Health Board as part of a larger study. Ten people with a definite
      diagnosis of MS were purposefully selected aiming for diversity on a range of
      characteristics. RESULTS: A number of factors were identified that seemed to
      interact and work to tip the decisional balance regarding physical activity
      engagement for people with MS. The most prominent themes included beliefs about
      physical activity; related emotional responses; and the role of fatigue in the
      decision to take part in physical activity. One of the most striking findings was
      the apparent tension surrounding the decision to take part in physical activity
      which seemed to be related to the co-existence of conflicting beliefs.
      CONCLUSIONS: For people with MS, the decision to engage in physical activity (or
      not) is complex, fluid and individual; made more complex by the unpredictable
      nature of MS. Rehabilitation professionals attempting to engage people with MS in
      a physical activity programme should consider adopting an individualised approach
      to barrier management which takes into account personal beliefs and perceptions
      regarding physical activity engagement.

PMID- 20695817
TI  - Experiences of decreased lung function in people with cervical spinal cord
      injury.
AB  - PURPOSE: The present aim was to explore and describe experience of decreased lung
      function among people with cervical spinal-cord injury (CSCI). METHOD: Thirty
      three people with CSCI with a lesion between levels C4 and C8 entered the study.
      Qualitative content analysis was used. A semi-structured interview guide was
      constructed with the main focus on experience of symptoms related to decreased
      lung function. RESULTS: The experience related to decreased lung function was
      limitations in breathing function, the ability to cough and voice function.
      Individual self-management strategies were described in relation to these
      limitations. The overarching theme throughout the interviews was that although
      the limitations were in most cases significant compared to the situation before
      injury, they were not necessarily experienced or referred to as a problem.
      CONCLUSIONS: Breathing function, the ability to cough and voice function were
      perceived as limited in most of the present participants with CSCI compared to
      before the injury. Most had adapted to the situation and had developed their own
      strategies for handling the limitations. However, these limitations did not only
      become normal for the individuals because of compensatory strategies, these
      limitations were usually experienced as a problem not to speak of.

PMID- 20695818
TI  - The lived experience of art making as a companion to the mental health recovery
      process.
AB  - PURPOSE: Art making is a common activity provided for consumers in mental health
      psychosocial rehabilitation services, yet there is little evidence available
      which examines its role in the recovery process. The current study inquires into
      mental health consumers' lived experiences of art making within psychosocial
      rehabilitation services and their views on how art making supports mental health
      recovery. METHOD: This research used qualitative in-depth interviews to explore
      the role of art making in the mental health recovery journey. The sample
      comprised 18 consumer participants who attended art-based programs in two
      psychosocial services in Victoria, Australia. The 60-90 min interviews were
      analysed using interpretative phenomenological analysis. RESULTS: A total of 11
      major themes were identified and organised into three areas: qualities conducive
      to the art making context, how the art making process benefits mental health
      recovery, and how the image or art product benefits mental health recovery. The
      11 themes are described and illustrated from participant interviews. Consumers
      described art making as a transformative activity which enabled them to take
      greater control of their lives, resulting in feeling stronger, more confident,
      and more capable of driving their journey of recovery. The art product also
      served valuable roles in supporting their recovery. CONCLUSIONS: Art making is a
      highly valued activity by consumers, who suggest that innovative and strengths
      based methods, such as art making, can facilitate recovery and self-expression. A
      key challenge for the field is to determine how such methods can be better
      integrated into mental health service delivery.

PMID- 20695819
TI  - Interview with Prof. Dr. Augustinus Bader. Interview by Vicki Glaser.

PMID- 20695821
TI  - Recombinant human erythropoietin plays a pivotal role as a topical stem cell
      activator to reverse effects of damage to the skin in aging and trauma.

PMID- 20695822
TI  - Functional genomics of drug-induced ion homeostasis identifies a novel regulatory
      crosstalk of iron and zinc regulons in yeast.
AB  - Pyrrolidine dithiocarbamate (PDTC), a known inhibitor of NFkappaB activation, has
      antioxidative as well as antiviral activities. PDTC is effective against several
      virus families, indicating that its antiviral mechanism targets host rather than
      viral functions. To investigate its mode of action, we used baker's yeast as a
      simple eukaryotic model system and two types of genome-wide analysis. First,
      expression profiling using whole-genome DNA microarrays identifies more than 200
      genes differentially regulated upon PDTC exposure. Interestingly, the Aft1
      dependent iron regulon is a main target of PDTC, indicating a lack of iron
      availability. Moreover, the PDTC-caused zinc influx triggers a strong regulatory
      effect on zinc transporters due to the cytoplasmic zinc excess. Second,
      phenotypic screening the EUROSCARF collection for PDTC hypersensitivity
      identifies numerous mutants implicated in vacuolar maintenance, acidification as
      well as in transport, mitochondrial organization, and translation. Notably, the
      screening data indicate significant overlaps of PDTC-sensitive genes and those
      mediating zinc tolerance. Hence, we show that PDTC induces cytoplasmic zinc
      excess, eliciting vacuolar detoxification, which in turn, disturbs iron
      homeostasis and activates the iron-dependent regulator Aft1. Our work reveals a
      complex crosstalk in yeast ion homeostasis and the underlying regulatory
      networks.

PMID- 20695823
TI  - Comparative analysis of transcriptome and fitness profiles reveals general and
      condition-specific cellular functions involved in adaptation to environmental
      change in Saccharomyces cerevisiae.
AB  - The transcriptional responses of yeast cells to a wide variety of stress
      conditions have been studied extensively. In addition, deletion mutant
      collections have been widely used to measure the combined effect of gene loss and
      stress on growth (fitness). Here we present a comparative analysis of 1,095
      publicly available transcription and genome-wide fitness profiles in yeast, from
      different laboratories and experimental platforms. We analyzed these data, using
      T-profiler, to describe the correlation in behavior of a priori defined
      functional groups. Two-mode clustering analysis of the fitness T-profiles
      revealed that functional groups involved in regulating ribosome biogenesis and
      translation offer general stress resistance. These groups are closely related to
      growth rate and nutrient availability. General stress sensitivity was found in
      deletion mutant groups functioning in intracellular vesicular transport, actin
      cytoskeleton organization, and cell polarity, indicating that they play an key
      role in maintaining yeast adaptability. Analysis of the phenotypic and
      transcriptional variability of our a priori defined functional groups showed that
      the quantitative effect on fitness of both resistant and sensitive groups is
      highly condition-dependent. Finally, we discuss the implications of our results
      for combinatorial drug design.

PMID- 20695824
TI  - Quantitative proteomic approaches and their application in the study of yeast
      stress responses.
AB  - The increasing popularity of proteomics has created a need for quantitative
      analysis methods. As a result, many different techniques are now available for
      performing gel-based or gel-free quantitative proteomic analysis of biological
      samples. These techniques provide an insight into global protein expression from
      identification to quantification, taking into account the highly dynamic status
      of the proteome. With its relatively small and compact genome, yeast is widely
      used as a model organism for molecular genetics, cell biology, and proteomic
      studies. In this review, we will show how quantitative proteomics has been used
      to study the effect of different stresses on yeast.

PMID- 20695825
TI  - Comparative functional genomics of stress responses in yeasts.
AB  - Systems biology proposes a multidisciplinary approach of biological systems, in
      order to obtain global and quantitative models of their functioning. This review
      presents an overview of 10 years of systemic analyses of the cellular responses
      to environmental stresses, using one of the favorite postgenomics models: the
      budding yeast Saccharomyces cerevisiae. These analyses include the global
      reconstruction and the dynamic modeling of the regulatory networks involved in
      the adaptation of the cells to environmental fluctuations and the extension of
      these approaches to other yeast species, to provide insights in the mechanisms
      that drive the evolution of the biological network properties.

PMID- 20695826
TI  - Antimicrobial prophylaxis in surgery: an international survey.
AB  - BACKGROUND: We investigated current clinical practice of antimicrobial
      prophylaxis (AMP) in surgery. METHODS: Survey administration of AMP to patients
      without co-morbidity or allergy undergoing surgery, among surgeons indexed as
      corresponding authors for articles published in general surgery, orthopedics,
      gynecology, and cardiac surgery journals. RESULTS: A total of 1,068 surgeons
      answered (response rate 68%). Of these, 26.1% do not begin infusion of the first
      antimicrobial dose within 1 h of incision, as suggested by guidelines, and 27.2%
      continue administering AMP for two or more days after surgery, including 7.6% who
      continue for four to seven days, in contradiction to the guidelines. There were
      significant differences between Europe and North America in the selection of AMP
      regimens. Furthermore, 19% of Europeans order infusion of the first antimicrobial
      dose during the incision compared with 3.9% of North Americans; 74.2% of
      Europeans discontinue AMP within 24 h after surgery compared with 86% of North
      Americans. Finally, 31% of general surgeons in North America administer
      supplementary oral prophylaxis for colectomy compared with only 5% of European
      surgeons. CONCLUSIONS: The AMP strategies in day-to-day self-reported practice
      differ significantly. Uniform, evidence-based practice is warranted, especially
      in this era of increasing antimicrobial resistance.

PMID- 20695827
TI  - Unusual locations of hydatid disease: diagnostic and surgical management of a
      case series.
AB  - BACKGROUND: Hydatid disease is endemic in many areas of the world, where it is an
      important public health problem. The aim of this study was to describe a series
      of patients with atypically located primary hydatid disease, accompanied by a
      literature review. METHODS: Six male and four female patients with atypically
      located hydatid cysts who presented to the Kars State Hospital between September
      2004 and March 2008 were evaluated. The mean age was 42.5 years (range 17-72
      years). Hydatid cysts were identified by using a combination of serology tests,
      ultrasonography, and computed tomography (CT). RESULTS: Six of the patients
      underwent surgical treatment. Three patients (two with pericardial hydatid
      involvement and one with pancreatic involvement) were sent to a tertiary medical
      center for surgery, and one patient died from cardiac and renal failure two days
      after diagnosis. CONCLUSIONS: Although this disease is seen most often in the
      liver and lungs, it can be found in any part of the body. Hydatid disease must be
      considered in the differential diagnosis of cystic lesions, especially in
      patients who have spent time in endemic areas.

PMID- 20695828
TI  - Microbiology of surgical site infections complicating breast surgery.
AB  - BACKGROUND: Surgical site infection (SSI) rates complicating breast surgery have
      ranged from 1-26%, but limited data have been provided regarding pathogen
      identification and in vitro susceptibility results. The aim of this study was to
      evaluate the results of bacterial cultures of breast SSI sites and antibiotic
      susceptibility testing to determine the clinical utility of these findings. STUDY
      DESIGN: Medical records were reviewed for SSI in patients who had undergone
      breast/axillary surgical procedures between June 2003 and June 2006. An SSI was
      defined by the criteria of the U.S. Centers for Disease Control and Prevention.
      Clinical data were collected on perioperative prophylactic antibiotics, organisms
      isolated, and resistance profiles. RESULTS: A total of 832 breast/axillary
      operations in 683 patients were included. Material was available for culture in
      67/144 SSI (47%), but cultures were obtained from only 41 of these sites (61%).
      There were 25 sites with positive bacterial cultures from which 35 organisms were
      isolated. Staphylococci were the organisms isolated most commonly (n = 21; 60%);
      14 other isolates (40%) included gram-negative bacilli and anaerobes.
      Susceptibility testing was performed on 16 (76%) of the staphylococcal isolates.
      Ten (63%) exhibited drug resistance; five were multi-drug resistant. Six of eight
      non-staphylococcal isolates tested (75%) exhibited antibiotic resistance; two
      were multi-drug resistant. CONCLUSIONS: Although the usual empiric treatment of
      SSI after breast surgery targets staphylococci, cultures with susceptibility
      profiles should be obtained because non-staphylococcal bacteria were commonly
      identified, and drug resistance was seen in more than one-half of the isolates.
      Further study is needed to define the optimal empiric antibiotic therapy for SSI
      after breast surgery.

PMID- 20695829
TI  - Epidemiologic trends, occurrence of extended-spectrum beta-lactamase production,
      and performance of ertapenem and comparators in patients with intra-abdominal
      infections: analysis of global trend data from 2002-2007 from the SMART study.
AB  - BACKGROUND: The Study for Monitoring Antimicrobial Resistance Trends (SMART) is
      an ongoing surveillance study to monitor worldwide resistance trends among
      aerobic and facultative anaerobic gram-negative bacilli isolated from intra
      abdominal infections (IAIs). Results from SMART in 2002 through 2005 have been
      reported; this report summarizes aggregated data from SMART 2002-2007 to identify
      epidemiologic trends over time. METHODS: A cumulative total of 446 sites were
      involved, of which 119, 166, 66, 28, and 67 were in Asia/Pacific, Europe, Latin
      America, Middle East/Africa, and North America, respectively. RESULTS: A total of
      34,635 isolates were collected from IAIs during 2002-2007, of which 32,113
      (92.7%) were from 12 species. The organisms isolated most commonly were
      Escherichia coli (47.6%), Klebsiella pneumoniae (12.9%), and Pseudomonas
      aeruginosa (9.5%). The most frequent infection source associated with the 12 most
      common organisms consistently was peritoneal (46%), followed by intestine (15.8%)
      and liver (3.2%), with the majority of the organisms originating from inpatients
      (90.7%), followed by outpatients (4.3%) and undetermined sources (5.0%).
      Approximately 52% of these isolates were from patients with a hospital stay of >
      or = 48 h, with 45.5% from patients with a hospital stay of < 48 h. Overall,
      ertapenem and imipenem consistently were the most effective antibiotics, whereas
      resistance to other agents was more common. CONCLUSIONS: Escherichia coli was the
      organism isolated most frequently from IAIs, of which the majority were from
      peritoneal and intestinal sources. Only the carbapenems maintained good activity
      against the majority of clinical isolates.

PMID- 20695830
TI  - Hospital experiences of older people with intellectual disability: responses of
      group home staff and family members.
AB  - BACKGROUND: This study reports on the hospitalisation experiences of older adults
      with intellectual disability living in group homes. METHODS: Grounded dimensional
      analysis was used to guide data collection and analysis. Group home residents
      were tracked prospectively over a 3-year period. Interviews were conducted with
      family, group home, and aged care staff and managers, and some residents.
      RESULTS: Findings highlighted the difficulty people with intellectual disability
      experience in hospital settings. Findings revealed extensive strategies
      undertaken by family members and group home staff to improve hospital
      experiences. Ageing of the family members and staffing implications for group
      homes complicated efforts to improve hospital experiences. CONCLUSIONS: The
      current absence of systems to accommodate the special needs of people with
      intellectual disability in hospital settings has significant consequences for
      group homes, family members, hospital staff, and residents. Most hospital systems
      appear to be poorly designed to care for this vulnerable population.

PMID- 20695831
TI  - Management of complicated gallstones: results of an alternative approach to
      difficult cholecystectomies.
AB  - Laparoscopic cholecystectomy (LC) is the gold standard treatment of gallstones.
      Nevertheless, the incidence of conversion and injuries to the biliary tract is
      still high in difficult cholecystectomies. In this study we sought to determine
      how using operative risk predictive scores (PSs) and the Nassar scale to grade
      the difficulty of LC would optimize the perioperative management of complicated
      gallstone patients. We also evaluated whether the "fundus-first" approach to LC
      combined with ultrasonic dissection minimizes the risk of conversion and biliary
      injury in difficult cholecystectomies, and avoids routine intraoperative
      cholangiography. A prospective non-randomized study was carried out from 2005 to
      2007 including 237 patients referred for gallbladder diseases. All patients were
      evaluated using an operative risk PS. The LC grade of difficulty was assessed
      according to Nassar. Diagnostic accuracy, sensitivity, and specificity of PS were
      calculated. LC in difficult cases was accomplished with a fundus-first approach.
      Outcome measures included: Conversion rate, bile duct (BD) injury rate, and
      postoperative complications according to Clavien. In 178 out of 237 patients, a
      higher risk of conversion and complication was predicted. In 146 out of these 178
      cases, intra-operative grading confirmed the difficulty of the procedure. The PS
      diagnostic accuracy was 0.865, sensitivity was 100%, and specificity 65%.
      Positive predictive value and negative predictive value were 0.82 and 1,
      respectively. Conversion rate was 2.7%. Mean operating time and postoperative
      length of hospital stay were 75 minutes and 3.5 days. Intra-operative
      cholangiography was necessary in five cases, and one intraoperative biliary
      complication occurred with an uneventful postoperative course. Overall,
      postoperative complications were 2.7% with a mortality rate of 0.68% (1
      myocardial infarction). Fundus-first LC by ultrasonic dissection is safe and
      minimizes the risk of conversion and biliary injuries in difficult cases.
      Difficult cholecystectomies may be predicted preoperatively; in these cases the
      fundus-first approach and ultrasound dissection may be advised.

PMID- 20695832
TI  - "See and treat" hysteroscopy after missed abortion.
AB  - A prospective study was conducted on the incidence of intrauterine pathology
      after missed abortion diagnosed and treated by hysteroscopy. A hysteroscopy was
      performed in 100 women four to 12 weeks after a dilatation and curettage for
      missed abortions. Uterine malformations were found in 12 patients, intrauterine
      adhesions in seven and submucous myoma in two cases. As a side finding four cases
      of asymptomatic retained products of conception were found. Most cases of the
      intrauterine pathology were treated instantly by hysteroscopy, "see and treat"
      regimen was preferred. Post-missed abortion-hysteroscopy is a simple and useful
      method for early diagnosis and treatment of congenital and acquired intrauterine
      pathology.

PMID- 20695834
TI  - HER3 mRNA as a predictive biomarker in anticancer therapy.
AB  - IMPORTANCE OF THE FIELD: Heterodimerization of human EGF receptor (HER) 2 and
      HER3, a co-receptor of HER2, plays an important and dominant role in the
      functionality and transformation of HER-mediated pathways. Understanding the role
      of HER3 in oncogenesis as well as its place as a target for anticancer therapy is
      an ongoing area of research. Determination of biomarkers for clinical benefit
      from agents targeting HER3 is an essential component of translating basic science
      into real-world effective anticancer therapies, with the aim of ensuring the
      patients most likely to benefit from such treatments can be identified. AREAS
      COVERED IN THIS REVIEW: This review focuses on the targeting of HER2 and HER3 by
      monoclonal antibodies and the potential for HER3 mRNA levels to predict treatment
      outcome in ovarian cancer. WHAT THE READER WILL GAIN: An understanding of the
      value of biomarkers for clinical benefit to anticancer therapy and the current
      status of HER3 mRNA as a biomarker for clinical benefit of the HER2-HER3
      dimerization inhibitor pertuzumab. TAKE HOME MESSAGE: HER3 mRNA levels may be a
      biomarker for active ligand-induced HER2-HER3 signaling, with low HER3 mRNA
      levels correlated with clinical benefit from the HER2-HER3 dimerization inhibitor
      pertuzumab.

PMID- 20695833
TI  - Ivermectin-loaded microparticles for parenteral sustained release: in vitro
      characterization and effect of some formulation variables.
AB  - Ivermectin (IVM) is a BCS II drug with potent antiparasitic activity in
      veterinary applications. In this study, poly(lactide-co-glycolide) (PLGA) and
      poly(DL-lactide) (PLA) Ivermectin-loaded microparticles were prepared by the
      simple emulsion (O/W) solvent evaporation method in order to obtain sustained
      release formulations for parenteral applications. The effects of polymer end
      groups (ester or free acid) and the addition of the hydrophilic
      polyvinylpyrrolidone polymer (PVP) in in vitro drug release profiles were also
      studied. X-ray diffraction (XRD) and differential scanning calorimetry (DSC)
      analysis showed that IVM was present in an amorphous state or as a molecular
      dispersion within the polymers or theirs mixtures with PVP and that a PVP-drug
      complex was formed. Drug entrapment efficiency in the microparticles (>90%) was
      independent of the polymer composition, the end groups and the presence of PVP.
      However, microscopic (SEM) observations showed that the addition of PVP led to
      more porous microparticles accompanied by the increased rates of drug release.

PMID- 20695835
TI  - GM-CSF pathway correction in pulmonary alveolar proteinosis.
AB  - IMPORTANCE OF THE FIELD: Pulmonary alveolar proteinosis (PAP) is a rare disease
      in which the abnormalities in surfactant metabolism are caused most often by
      impairments of GM-CSF pathway at different levels in different disease subsets
      (congenital, secondary, acquired/idiopathic) and for which there are only few,
      costly invasive therapeutic methods. AREAS COVERED IN THIS REVIEW: This review
      discusses these impairments, and their pathogenic and clinical consequences along
      with potential corrective therapies such as exogenous inhaled GM-CSF. WHAT THE
      READER WILL GAIN: Among the PAP disease subsets, in autoimmune PAP the GM-CSF
      autoantibodies play a major role in disease pathogenesis and their deleterious
      pulmonary effects can be blocked efficaciously with inhaled GM-CSF. TAKE HOME
      MESSAGE: In PAP correction of the abnormalities of the GM-CSF pathway represent a
      plausible approach demonstrated to be efficacious also in the case of inhaled GM
      CSF used for autoimmune PAP.

PMID- 20695836
TI  - Norovirus non-structural protein p20 leads to impaired restitution of epithelial
      defects by inhibition of actin cytoskeleton remodelling.
AB  - OBJECTIVE: Norovirus is the most common cause of acute gastroenteritis in humans
      worldwide. Typical symptoms are vomiting, nausea and severe watery diarrhea.
      Because of the lack of cell lines susceptible to human norovirus infection,
      pathomechanisms and replication cycle are largely unknown. Here, we address the
      issue of how norovirus infection could lead to epithelial barrier dysfunction.
      MATERIAL AND METHODS: Expression of the non-structural norovirus protein p20 in
      the epithelial cell line HT-29/B6 was activated through a tetracycline sensitive
      promoter. Tight junction proteins were studied by Western blot and confocal laser
      scanning microscopy. Apoptoses were detected in TUNEL stainings. Epithelial
      restitution was monitored by conductance scanning after induction of single cell
      lesions. RESULTS: Changes in the expression or localization of the tight junction
      proteins occludin and/or claudin-1, -2,- 3, -4, -5, -7 and -8 could be ruled out
      to mediate epithelial barrier modulation. Cell motility was also unaltered by
      p20. Investigation of epithelial apoptosis revealed an accumulation of apoptic
      cells in epithelial monolayers after induction of p20 expression. In epithelial
      cell restitution assays, an arrest was identified in p20 expressing cells.
      Fluorescence microscopy revealed an inability for condensation and redistribution
      of cellular actin, which led to a reduced transepithelial electrical resistance.
      CONCLUSIONS: Functional data for norovirus protein p20 suggest a role in
      modulation of the actin cytoskeleton leading to barrier dysfunction through
      impairment of restitution of epithelial defects.

PMID- 20695837
TI  - Magnetically responsive paclitaxel-loaded biodegradable nanoparticles for
      treatment of vascular disease: preparation, characterization and in vitro
      evaluation of anti-proliferative potential.
AB  - Long term prevention of smooth muscle cell migration and proliferation inside the
      lumen of coronary arteries after stent implantation remains a challenge in
      medicine. Vascular stents have been coated with anti-proliferative drugs such as
      paclitaxel and rapamycin to improve the stents' efficacy. Maintaining adequate
      drug concentration on coronary stents presents an obstacle which magnetic
      nanoparticle (MNP) drug delivery could potentially overcome. Biodegradable, super
      paramagnetic nanoparticles guided by high gradient magnetic fields have been
      proposed as transport vehicles for re-dosing stents with anti-proliferative
      drugs. The current study determined the characteristics of a number of candidate
      MNP formulations in terms of their size, surface charge, efficiency of magnetite
      and drug loadings, drug release profiles as well as their anti-proliferative
      effect on the relevant vascular cells. MNPs containing near 30% (w/w) magnetite
      and 12% (w/w) paclitaxel were formulated from polylactide and poly(lactide-co
      glycolide) polymers using an emulsification-solvent evaporation methodology. Drug
      release patterns correlated well with cell growth inhibition in cultured aortic
      smooth muscle cells and bovine aortic endothelial cells treated with varying MNP
      doses. Cell viability assays revealed MNP dose-dependent cell growth inhibition
      over an 8-day time span for paclitaxel-loaded formulations resulting in near 80%
      and 100% of cell growth arrest in cultured vascular smooth muscle cells and
      endothelial cells respectively, while unloaded with drug formulations showed
      negligible variation from the non treated cells. It is concluded, that
      biodegradable polymeric superparamagnetic nanoparticles loaded with a relatively
      high level of magnetite and drug could serve as efficient carriers in vascular
      stent targeting applications and potentially allow re-dosing the depleted stents,
      thereby prolonging the lifecycle of the implant.

PMID- 20695838
TI  - Phosphodiesterase-5 inhibitor tadalafil acts on endothelial progenitor cells by
      CXCR4 signalling.
AB  - It has been proposed that endothelial progenitor cells (EPC), originating from
      the bone marrow contribute to neo-angiogenesis in vivo by forming endothelial
      cells. Once released in the bloodstream, EPC home at the site of vascular damage
      where they participate in endothelium regeneration. In this process CXCR4 plays a
      key role. Recently we demonstrated that a prolonged therapy with
      phosphodiesterase-5 (PDE5) inhibitors does improve endothelial function and
      increases circulating EPC, suggesting a role of PDE5 in EPC physiology. Here we
      tested the expression of PDE5 and CXCR4 on cultured, circulating, and bone marrow
      resident EPC, and we studied the effect in vivo and in vitro of PDE5 inhibition
      after administration of a PDE5 inhibitor (tadalafil) on EPC, in term of CXCR4
      expression. We documented that in vivo and in vitro EPC express both PDE5 and
      CXCR4, and that tadalafil administration induced a significant increase in EPC
      number and the relative CXCR4 expression. This effect is inhibited by selective
      CXCR4 antagonist. We thus demonstrated that PDE5 inhibition acts on CXCR4
      signalling in EPC and we can suppose an involvement of cGMP second messenger
      system in both EPC release from the bone marrow and EPC-mediated peripheral re
      endothelization.

PMID- 20695839
TI  - Topical dermatological drug delivery: quo vadis?
AB  - Skin disease (dermatological conditions') affects at least one-third of the US
      population and has been cited as one of the top 15 medical conditions for which
      prevalence and healthcare spending increased in the last decade. The outcome of
      topical dermatological drug treatment is significantly influenced by the choice
      of vehicle or delivery system. Advancements in the life sciences coupled with a
      growing market for dermatologicals have facilitated the emergence of improved
      topical formulations and drug delivery systems. The current and emerging
      approaches of optimizing the topical delivery of dermatological agents (small and
      large molecules) include the use of chemical enhancers, bio-polymers (e.g. sodium
      hyaluronate), liposomes, particulate carriers (microspheres and lipid
      nanoparticles), topical sprays and foams, occlusion (via dressings and patches)
      topical peels, temperature (heat), iontophoresis, and ultrasound. These delivery
      approaches (when used solely or in a synergistic manner) are a significant
      improvement over conventional systems (creams, lotions, ointments and pastes) and
      have the potential to enhance efficacy and tolerability, improve patient
      compliance (including dermatology life quality), and also fulfil other unmet
      needs of the topical dermatological market.

PMID- 20695840
TI  - Release of antithrombotic drugs from alginate gel beads.
AB  - The aim of the present work was to evaluate alginate hydrogels in the form of
      spherical beads as carrier for antithrombotic drugs for future use in artificial
      grafts. The ionotropic gelation technique was employed to prepare beads from the
      L. hyperborea stipe of alginate with two different alginate concentrations and
      two different guluronic to manuronic acid ratios. The beads were loaded, via
      soaking, with three different types of low molecular weight model molecules
      representing drugs with antithrombotic action and their release characteristics
      were subsequently evaluated. The entire release process of the negatively charged
      model drugs under study (Salicylic acid and Hirudin), was found to be governed by
      diffusion, while additional electrostatic interactions between drug molecule and
      alginate matrix was indicated to influence the release rate of the analyzed
      positively charged drug molecule (Dipyridamole). It was found that the alginate
      hydrogel matrix imposed a decrease of the drug diffusion rate on the molecules
      under study as compared to the corresponding diffusion rates in water. All
      diffusion coefficients decreased slightly with increasing concentration of
      alginate and with increasing guluronic to manuronic acid ratio. The results show
      on the potential use of alginate gel beads when developing vehicles for release
      of low molecular weight antithrombotic drugs.

PMID- 20695841
TI  - Nanoparticles: a promising therapeutic approach in atherosclerosis.
AB  - Coronary atherosclerosis is the largest cause of mortality and morbidity in
      industrialised countries. Despite recent advances in medical therapies, the
      prevention and treatment of atherosclerosis remain suboptimal. Atherosclerosis is
      considered to be a chronic inflammatory disease of the arterial wall, involving
      the accumulation of macrophages and excess low density lipoproteins (LDL), the
      formation of foam cells which create the atheromatous plaque, resulting in
      stenosis, aneurysm and plaque rupture leading to acute coronary events. Every
      step in the atherogenesis process is a potential therapeutic target for both the
      prevention and regression of atherosclerosis. A novel approach is the use of
      nanoparticles containing drugs, providing new perspectives in targeted
      modification of these pathways. Nanoparticles are ultrafine particles sized
      between 1-100 nm. By using specific methods, nanoparticles can be filled with
      drugs and achieve targeted drug delivery near the diseased area. In this review
      article we describe the basic actions of nanoparticles, and we discuss their
      potential applications in atherosclerosis. We also discuss their advantages and
      we expose the existing toxicity issues, making it clear however, that the use of
      nanoparticles is one of the most promising therapeutic strategies against
      atherosclerosis.

PMID- 20695842
TI  - Chloroquine resistance: proposed mechanisms and countermeasures.
AB  - Malaria has been, and remains, one of the biggest global health concerns as far
      as infectious diseases are concerned, with yearly incidence and mortality figures
      running into millions. One of the major drawbacks to the control of this disease
      has been the emergence of drug resistant strains of the causative agent, which
      limits the successful use of many clinically available antimalarial drugs. This
      review discusses chloroquine resistance; it highlights some of the proposed
      molecular mechanisms of chloroquine resistance, but dwells more on efforts at
      reversing chloroquine resistance and the concept of chloroquine resistance
      reversal agents.

PMID- 20695843
TI  - Evaluation of extemporaneously manufactured topical gels containing aceclofenac
      on inflammation and hyperalgesia in rats.
AB  - The systemic use of non-steroidal anti-inflammatory drugs (NSAIDs) which act by
      inhibiting cyclooxygenase (COX) is severely hampered by gastric and peptic
      ulcers. The topical delivery of NSAIDs has the advantages of avoiding gastric and
      peptic ulcers and delivering the drug to the inflammation site. Importance of
      aceclofenac as a new generational NSAID has inspired the development of topical
      dosage forms. This mode of administration may help to avoid typical side effects
      of NSAIDs associated with oral and systemic administration such as gastric
      irritation, particularly diarrhoea, nausea, abdominal pain and flatulence. The
      aim of this study was to formulate topical gel containing 1% of aceclofenac in
      carbopol and PEG base and to evaluate it for analgesic and antiinflammatory
      activity using carrageenan-induced thermal hyperalgesia and paw oedema in rats.
      Carrageenan administration into the hind paw produced a significant inflammation
      associated with hyperalgesia as shown by decreased rat paw withdrawal latency in
      response to a thermal stimulus (47+/-0.5 degrees C) 4 h after carrageenan
      injection. Topical application of AF1 significantly attenuated the development of
      hypersensitivity to thermal stimulus as compared to control (P<0.05) and other
      formulation treated groups (P<0.05). All the AF semisolid formulations, when
      applied topically 2 h before carrageenan administration, inhibited paw edema in a
      timedependent manner with maximum percent edema inhibition of 80.33+/-2.52
      achieved with AF1 after 5 h of carrageenan administration However, topical
      application of AF2 markedly prevented the development of edema as compared to
      other formulation (AF2 and AF3) treated groups (P<0.05). Among all the semisolid
      formulations, Carbopol gel base was found to be most suitable dermatological base
      for aceclofenac.

PMID- 20695844
TI  - Effect of iontophoresis and permeation enhancers on the permeation of an
      acyclovir gel.
AB  - The purpose of the present study was to explore the combined effect of chemical
      enhancers and iontophoresis on the in vitro permeation of acyclovir gel across
      porcine skin. Acyclovir gel was formulated using carbopol 940 and hydroxypropyl
      methylcellulose K4M (HPMC K4M). Effect of drug concentration on the delivery of
      acyclovir was examined. Increasing drug concentration of acyclovir enhanced its
      flux across the skin. Incorporation of permeation enhancers (menthol, n-methyl-2
      pyrrolidone and polyethylene glycol 400) into the gel resulted in enhanced
      acyclovir permeation when combined with iontophoresis. Menthol showed the highest
      drug permeation and when combined with iontophoresis it significantly increased
      the acyclovir skin permeation.

PMID- 20695845
TI  - Utilization of hydrophilic swellable polymers as carriers for sustained drug
      delivery from matrices and three layer tablet systems.
AB  - The purpose of this research was to develop and evaluate different sustained
      release preparations, using swellable polymers as carriers in the form of
      matrices and three-layer tablets. These preparations may offer a number of
      therapeutic advantages over immediate release dosage forms in drug delivery. The
      materials used for the fabrication of these systems were hydrophilic swellable
      polymers namely Metolose, Polyox, Xanthan gum and an erodible material Gantrez,
      acting as drug(diclofenac sodium) carriers. The powder characteristics determined
      for these polymers suggest good flowability with the exception of Gantrez. The
      addition of 1% of magnesium stearate resulted in improved flow properties for all
      polymers including Gantrez. Tablets were prepared by direct compression whereas
      three-layer tablets were prepared by compressing polymer barrier layers on both
      sides of the core containing the drug. Our findings show that both preparations
      exhibit sustained release characteristics; also the structure of the device
      considerably affects the drug release and the release rate. Furthermore erosion
      and swelling greatly influence the overall behavior, function and performance of
      the systems. Finally kinetic analysis studies indicated that the drug release
      mechanisms were also affected by these effects.

PMID- 20695846
TI  - The inhibition of monocarboxylate transporter 2 (MCT2) by AR-C155858 is modulated
      by the associated ancillary protein.
AB  - In mammalian cells, MCTs (monocarboxylate transporters) require association with
      an ancillary protein to enable plasma membrane expression of the active
      transporter. Basigin is the preferred binding partner for MCT1, MCT3 and MCT4,
      and embigin for MCT2. In rat and rabbit erythrocytes, MCT1 is associated with
      embigin and basigin respectively, but its sensitivity to inhibition by AR-C155858
      was found to be identical. Using RT (reverse transcription)-PCR, we have shown
      that Xenopus laevis oocytes contain endogenous basigin, but not embigin. Co
      expression of exogenous embigin was without effect on either the expression of
      MCT1 or its inhibition by AR-C155858. In contrast, expression of active MCT2 at
      the plasma membrane of oocytes was significantly enhanced by co-expression of
      exogenous embigin. This additional transport activity was insensitive to
      inhibition by AR-C155858 unlike that by MCT2 expressed with endogenous basigin
      that was potently inhibited by AR-C155858. Chimaeras and C-terminal truncations
      of MCT1 and MCT2 were also expressed in oocytes in the presence and absence of
      exogenous embigin. L-Lactate Km values for these constructs were determined and
      revealed that the TM (transmembrane) domains of an MCT, most probably TM7-TM12,
      but not the C-terminus, are the major determinants of L-lactate affinity, whereas
      the associated ancillary protein has little or no effect. Inhibitor titrations of
      lactate transport by these constructs indicated that embigin modulates MCT2
      sensitivity to AR-C155858 through interactions with both the intracellular C
      terminus and TMs 3 and 6 of MCT2. The C-terminus of MCT2 was found to be
      essential for its expression with endogenous basigin.

PMID- 20695847
TI  - Antimicrobial and immunostimulatory peptide, KLK, induces an increase in
      cytosolic Ca2(+) concentration by mobilizing Ca2(+) from intracellular stores.
AB  - The cationic antimicrobial immunomodulatory peptide, KLK (KLKL5KLK), exerts
      profound membrane interacting properties, impacting on ultrastructure and
      fluidity. KLK-membrane interactions that lead to these alterations require the
      ability of the peptide to move into an alpha-helical conformation. We show that
      KLK induces an increase of the intracellular Ca2(+) concentration in human T24
      cells. The effect of KLK is buffer-sensitive, as it is detected when HBSS buffer
      is used, but not with PBS. This, together with the lack of effect of the middle
      leucine-to-proline-substituted peptide derivative [KPK (KLKLLPLLKLK)], indicates
      that it is the conformational propensity rather than the net positive charge that
      contributes to the effect of KLK on intracellular Ca2(+) level of T24 cells. We
      show that, although KLK slightly stimulates Ca2(+) influx into the cell, the bulk
      increase of Ca2(+) levels is due to KLK-induced depletion of intracellular Ca2(+)
      stores. Finally, we demonstrate a KLK-induced switch of PS (phosphatidylserine)
      from the inner to the outer plasma membrane leaflet that contributes to the onset
      of early apoptotic changes in these cells.

PMID- 20695848
TI  - Munc18b regulates core SNARE complex assembly and constitutive exocytosis by
      interacting with the N-peptide and the closed-conformation C-terminus of syntaxin
      3.
AB  - The interaction between SM (Sec1/Munc18) and SNARE (soluble N-ethylmaleimide
      sensitive factor-attachment receptor) proteins constitutes the core eukaryotic
      membrane fusion machinery which manages exocytosis by mediating fusion of
      constitutively exocytic vesicles with the plasma membrane. However, mechanistic
      details on the nature and the physiological impact of SM-SNARE interactions
      remain largely elusive. Detailed characterization of the interaction profiles
      between Munc18b and its cognate SNAREs, Stx3 (syntaxin 3), SNAP-23 (soluble N
      ethylmaleimide-attachment protein 23) and VAMP8 (vesicle-associated membrane
      protein 8), revealed that Munc18b binds Stx3, VAMP8 and the assembled core SNARE
      complex consisting of Stx3, SNAP-23 and VAMP8. Dissection of the Munc18b-Stx3
      heterodimer suggested that Munc18b interacts with Stx3's conserved N-peptide as
      well as with its closed-conformation C-terminus encompassing the Habc domain, a
      linker and the SNARE (H3) motif. Deletion of the Habc domain or mutations
      interrupting the intramolecular binding of the Habc and H3 domains abrogated the
      Munc18b-Stx3 interaction. Although only the N-peptide deletion mutant, but not
      the soluble wild-type Stx3, is assembled into the core SNARE complex in the
      presence of Munc18b in vitro, ectopic expression of this SM protein increases
      constitutive exocytosis in mammalian cells. Our results suggest that Munc18b is
      functionally coupled to the assembly of exocytic SNARE complexes and increases
      exocytosis by interacting with the N-peptide and closed-conformation C-terminus
      of Stx3, thereby neutralizing the secretion-inhibitory effect of this SNARE.

PMID- 20695849
TI  - Glucose promotion of GABA metabolism contributes to the stimulation of insulin
      secretion in beta-cells.
AB  - We have demonstrated recently that branched-chain alpha-keto acid stimulation of
      insulin secretion is dependent on islet GABA (gamma-aminobutyric acid)
      metabolism: GABA transamination to succinic semialdehyde is increased by 2
      oxoglutarate, generated in alpha-keto acid transamination to its corresponding
      alpha-amino acid. The present work was aimed at investigating whether glucose
      also promotes islet GABA metabolism and whether the latter contributes to the
      stimulation of insulin secretion. Glucose (20 mM) decreased both the content and
      release of islet GABA. Gabaculine (1 mM), a GABA transaminase inhibitor,
      partially suppressed the secretory response of rat perifused islets to 20 mM
      glucose at different L-glutamine concentrations (0, 1 and 10 mM), as well as the
      glucose-induced decrease in islet GABA. The drug also reduced islet ATP content
      and the ATP/ADP ratio at 20 mM glucose. Exogenous succinic semialdehyde induced a
      dose-dependent increase in islet GABA content by reversal of GABA transamination
      and a biphasic insulin secretion in the absence of glucose. It depolarized
      isolated beta-cells and triggered action potential firing, accompanied by a
      reduction of membrane currents through ATP-sensitive K(+) channels. The gene
      expression and enzyme activity of GABA transaminase were severalfold higher than
      that of 2-oxoglutarate dehydrogenase in islet homogenates. We conclude that, at
      high glucose concentrations, there is an increased diversion of glucose
      metabolism from the citric acid cycle into the 'GABA shunt'. Semialdehyde
      succinic acid is a cell-permeant 'GABA-shunt' metabolite that increases ATP and
      the ATP/ADP ratio, depolarizes beta-cells and stimulates insulin secretion. In
      summary, an increased islet GABA metabolism may trigger insulin secretion.

PMID- 20695850
TI  - Is the modulatory effect of pregnancy in multiple sclerosis associated with
      changes in blood apoptotic molecules?
AB  - OBJECTIVE: We examined whether the modulatory effect of pregnancy on multiple
      sclerosis (MS) is associated with changes in the apoptotic molecules in sera.
      SUBJECTS AND METHODS: The serum levels of tumor necrosis factor-related apoptosis
      inducing ligand (sTRAIL), sFas, Fas ligand (sFasL) and macrophage migration
      inhibitory factor were analyzed from 19 MS patients and 14 controls during late
      pregnancy and post-partum. The obtained results were related to disease activity
      and the progression of MS. RESULTS: Disease activity decreased during pregnancy.
      The levels of sTRAIL and sFasL increased from late pregnancy to post-partum
      situation in both MS patients and controls, but in MS patients the changes in the
      levels of sTRAIL from late pregnancy to post-partum were smaller than in
      controls. CONCLUSIONS: Post-partum upregulation of TRAIL and FasL seems to be
      caused by physiologic reactivation of the mother's immune system after pregnancy.
      An increased risk of relapses in MS post-partum may be associated with changes in
      the immunomodulatory potential of these apoptotic molecules.

PMID- 20695851
TI  - Minimum standard and learning outcomes in physiology required by the Bologna
      process: the Federation of European Physiological Societies end-terms of
      physiology in a medical curriculum.

PMID- 20695852
TI  - New insights into hereditary angio-oedema: Molecular diagnosis and therapy.
AB  - Hereditary angio-oedema (HAE) is a rare but potentially life-threatening
      condition. Three types are now recognized. Types I and II HAE involve mutations
      in the C1NH (SERPING1) gene, encoding the C1 inhibitor protein, whereas type III
      HAE involves mutations in the F12 gene, encoding coagulation factor XII (Hageman
      factor). They share a common final pathway leading to increased bradykinin
      formation. HAE must be distinguished from acquired angio-oedema with C1 esterase
      inhibitor deficiency, angiotensin-converting enzyme inhibitor-induced angio
      oedema and the much more common histaminergic angio-oedema, occurring with or
      without weals. Understanding the pathogenesis of HAE is leading to the
      introduction of new therapies that target the bradykinin receptor or inhibit
      kallikrein activity, innovations that will hopefully reduce morbidity and
      mortality in this group of severe genetic disease.

PMID- 20695853
TI  - Chronic telogen effluvium is due to a reduction in the variance of anagen
      duration.
AB  - BACKGROUND/OBJECTIVES: Chronic telogen effluvium and diffuse cyclical hair loss
      in women are well-described clinical entities characterized by chronic and
      fluctuating increases in hair shedding without loss of hair volume. We sought to
      investigate the follicular dynamics of chronic telogen effluvium and diffuse
      cyclical hair loss using a previously validated computer simulation known as the
      follicular automaton. METHODS: Using our model, we were able to simulate
      reductions in both the mean and variance of anagen duration and thus investigate
      their consequences with respect to both hair volume and hair shedding. RESULTS:
      We showed that reducing the mean anagen duration results in a loss of hair volume
      without prominent fluctuations in hair fall: findings that reproduced the key
      features in androgenetic alopecia. In contrast, a reduction in the variance of
      anagen duration generated follicular dynamics that accurately reproduced the
      known key features of chronic telogen effluvium and diffuse cyclical hair loss:
      acute exacerbations, periodicity and only minimal reductions in long-term hair
      volume. CONCLUSIONS: We provide evidence that suggests chronic telogen effluvium
      may be secondary to a reduction in the variance of anagen and suggest this
      pathological state represents a new functional type of recurrent hair shedding.

PMID- 20695854
TI  - Corticosteroid phobia and other confounders in the treatment of childhood atopic
      dermatitis explored using parent focus groups.
AB  - BACKGROUND/OBJECTIVES: Anxieties associated with corticosteroid treatment and
      preference for 'safer natural therapy' are common in parents of children with
      atopic dermatitis. We used focus groups to explore the source of these attitudes.
      METHODS: The study involved 16 parents. Parents expressed difficulties with
      living with and treating atopic dermatitis which were categorized into themes
      using qualitative data analysis software. RESULTS: Themes identified include:
      emotional impact of atopic dermatitis; difficulty in accepting 'control' verses
      'cure'; topical corticosteroid negative perceptions; anxiety and confusion with
      treatment; preference for 'natural' therapy; and attitude-changing positive
      experiences. CONCLUSIONS: Our findings illustrate the emotional impact of atopic
      dermatitis and the frustration with the lack of potential cure. 'Corticosteroid
      phobia' was universal among parents in our cohort and is a fear generated by
      doctors, pharmacists, close acquaintances and information from the internet.
      Participants expressed high levels of parental guilt linked to a desire for an
      eradicable 'cause' for atopic dermatitis, despite intellectually understanding
      this is a genetically determined condition. Parents were willing to change
      attitudes with accurate information from perceived reliable sources, positive
      hospitalization experiences and a relationship with a trusted dermatologist.
      Parents' suggestions to improve confidence included the provision of readily
      available information and better access to doctor- and nurse-led paediatric
      dermatology services.

PMID- 20695855
TI  - A randomized, assessor-blind, parallel-group, multicentre, phase IV comparative
      trial of a suffocant compared with malathion in the treatment of head lice in
      children.
AB  - BACKGROUND/OBJECTIVES: There are concerns about the effectiveness of head lice
      treatments because of increasing resistance and safety. This trial compared the
      safety and efficacy of a suffocant-based head lice treatment to malathion in
      children. METHODS: The trial used strict entry criteria, standardized treatment
      and assessment regimens, sibling treatment where appropriate and a primary
      efficacy end-point defined as the absence of live head lice. RESULTS: A total of
      216 children were enrolled. One hundred and sixty-nine were per-protocol. The
      suffocant was significantly more effective than malathion for the intention-to
      treat population (53.9% vs 40.4% louse-free, unadjusted P = 0.052; adjusted P =
      0.024), as well as for the per-protocol population (57.8% vs 43.0% louse-free,
      unadjusted P = 0.054; adjusted P = 0.045). Adverse events were limited to itching
      or stinging and there were no serious or systemic adverse events. Repeat insult
      patch testing with the suffocant resulted in no adverse reactions. In vitro tests
      confirmed that the suffocant is a potent ovicide and pediculicide with 100%
      mortality of eggs and lice following a 20-min contact time. CONCLUSIONS: The
      suffocant is shown to be significantly more effective in eliminating head lice
      than malathion in children, while being associated with a low incidence of mild,
      transient adverse events.

PMID- 20695856
TI  - Frontal fibrosing alopecia associated with generalized hair loss.
AB  - We present six cases of frontal fibrosing alopecia, in which generalized hair
      loss is a feature. Although this variant of lichen planopilaris has been reported
      clinically in a number of patients, there is very little histological evidence
      that the condition exists in peripheral sites. We believe this pattern of
      involvement may be more common than is reported, and have provided histological
      evidence of lichen planopilaris being present at sites beyond the scalp and
      eyebrows.

PMID- 20695857
TI  - Hidradenitis suppurativa responding to treatment with infliximab.
AB  - A series of four cases of severe recalcitrant hidradenitis suppurativa treated
      with infliximab is presented. All patients had failed to respond to prior medical
      and surgical management. Baseline Quantiferon-TB Gold and chest radiograph were
      carried out before commencement of treatment. No patients had associated Crohn's
      disease. All patients received induction infusions of infliximab 5 mg/kg at weeks
      0, 2 and 6, followed by eight weekly maintenance infusions. The total number of
      infusions varied between 4 and 6. Skin photography with Sartorius scoring was
      used to evaluate response to treatment. All patients experienced marked
      improvement in their disease activity, with a mean 48% improvement in Sartorius
      score after one infusion (week 2, P < 0.01), and 70% improvement after three
      infusions (week 14, P < 0.01). Time to relapse following cessation of therapy
      ranged from 6 weeks to 4 months. Further studies examining the efficacy of
      infliximab and its effect on the course of the disease, particularly relating to
      long-term management, are required.

PMID- 20695858
TI  - Facial porokeratosis: A series of six patients.
AB  - Porokeratosis is a disorder of epidermal keratinization characterized by annular
      plaques with an atrophic centre and hyperkeratotic edges, and includes a
      heterogeneous group of disorders that are mostly inherited in an autosomal
      dominant fashion. Facial porokeratosis is rare and is not well documented. We
      present six cases of facial porokeratosis seen over a period of 15 years in a
      hospital in Lima, Peru. In most of the cases, porokeratosis was found in younger
      women without any significant past medical history. Oral isotretinoin showed
      moderate improvement in two of our patients.

PMID- 20695859
TI  - Cutaneous leishmaniasis in a child treated with oral fluconazole.
AB  - We report a case of cutaneous leishmaniasis in a 3-year-old West African girl
      with a 3-month history of multiple disfiguring, infiltrated, ulcerating and
      variably necrotic granulomatous plaques on the limbs and face that occurred after
      swimming in a river approximately 6 weeks before arriving in Australia. A
      diagnosis of cutaneous leishmaniasis, a protozoal zoonosis usually transmitted by
      the Phlebotomus species of sandfly, was considered. The clinico-pathological
      features were consistent with Leishmania major infection, known to be the major
      endemic species causing cutaneous leishmaniasis in the country of origin. Because
      of the presence of lesions on the face, active treatment was instituted.
      Continuing resolution of all lesions over 6 weeks was noted to occur with
      cribiform scarring with the use of oral fluconazole 150 mg daily. Oral
      fluconazole appears to be emerging as a therapy for uncomplicated cutaneous
      leishmaniasis, with advantages particularly important in paediatrics.

PMID- 20695860
TI  - Sarcoidosis with cutaneous granulomatous vasculitis.
AB  - Ulceration of non-caseating granulomas is a rare cutaneous presentation of
      sarcoidosis. Granulomatous vasculitis is classically associated with Wegener's
      granulomatosis, lymphomatoid granulomatosis or Churg-Strauss syndrome. It is also
      commonly noted in pulmonary sarcoidosis, but has seldom been reported in
      cutaneous sarcoidosis, particularly the ulcerative variant. We present a rare
      case of sarcoidosis with multiple purpuric leg ulcers showing a granulomatous
      vasculitis histologically.

PMID- 20695861
TI  - Metastatic Merkel cell carcinoma with an unknown primary tumour presenting as
      lichenoid dermatitis.
AB  - Metastatic Merkel cell carcinoma uncommonly presents with an unidentified primary
      tumour. We report a patient who first presented with lichenoid dermatitis and was
      found to have Merkel cell carcinoma involving lymph nodes with an unknown primary
      site. With the rising incidence of Merkel cell carcinoma, it is important to
      recognize unusual manifestations of this disease as they may become more common
      in the future.

PMID- 20695862
TI  - Dystrophic calcification following neonatal heel-prick testing.
AB  - A 7-year-old boy presented with a 5-year history of dystrophic calcification
      manifesting as solitary nodules on the plantar aspect of both heels. Microscopic
      examination showed hyperkeratosis and psoriasiform hyperplasia overlying an area
      of dystrophic calcification. Multiple heel-prick tests carried out during the
      neonatal period to monitor blood glucose levels are the likely causative
      mechanism.

PMID- 20695863
TI  - Contact urticaria caused by a fluorescent dye.
AB  - A 28-year-old man developed urticaria while he was working in the garage. We
      suspected contact urticaria, which can be caused by some products used in his
      field, and we carried out a prick test using his work gloves and shoes. His
      gloves were orange and black in colour, his shoes were black and white in colour,
      and the materials they were made of were unknown. The results of the prick test
      using the gloves and shoes were positive. Gas chromatography/mass spectrometry
      was applied, and a fluorescent dye was found to be present in his gloves and
      shoes. The results of a prick test using the fluorescent dye were positive. His
      urticaria improved after he stopped using these gloves and shoes. This was a rare
      case of contact urticaria caused by a fluorescent dye in clothing.

PMID- 20695864
TI  - Psoriasis among Sarawakian natives in a tertiary skin centre in Sarawak.
AB  - A prospective cross-sectional study was done between December 2007 and June 2009
      in the skin clinic, Sarawak General Hospital, to determine the clinical
      characteristics of 138 Sarawakian natives with a clinical diagnosis of psoriasis.
      Women made up 50.7% and the mean age of the patients was 45.2 years. Of the
      group, 94.2% had chronic stable plaque psoriasis, 86.9% had a body surface area
      involvement of less than 10%, 60.9% had nail disease, 22.5% had joint disease and
      55.1% had minimal effects to their quality of life because of their psoriasis.

PMID- 20695865
TI  - Categorizing immunoflourescence mapping in epidermolysis bullosa with pyloric
      atresia: Use as a broad prognostic indicator.
AB  - Epidermolysis bullosa with pyloric atresia is a form of junctional epidermolysis
      bullosa associated with gastrointestinal abnormalities, which may include pyloric
      atresia. Genotype phenotype correlation is poorly understood and prognosis is
      difficult, if not impossible, to predict. Immunoflourescence mapping is an ideal
      candidate for developing a broad prognostic indicator for epidermolysis bullosa
      with pyloric atresia without the need for genetic mutation analysis. However, the
      tool developed in this paper does have limitations due to the small number of
      cases available and the effects of deleterious mutations in highly conserved
      cysteine residues on the predicted length of survival.

PMID- 20695866
TI  - Case of pretibial pruritic papular dermatitis. Letters to the editor.

PMID- 20695867
TI  - Rapid-growing juvenile xanthogranuloma: The reality of a second opinion
      teleconsultation. Letters to the editor.

PMID- 20695869
TI  - PlayStation purpura.
AB  - A 16-year-old boy presented with a number of asymptomatic pigmented macules on
      the volar aspect of his index fingers. Dermoscopy of each macule revealed a
      parallel ridge pattern of homogenous reddish-brown pigment. We propose that these
      lesions were induced by repetitive trauma from a Sony PlayStation 3 (Sony
      Corporation, Tokyo, Japan) vibration feedback controller. The lesions completely
      resolved following abstinence from gaming over a number of weeks. Although the
      parallel ridge pattern is typically the hallmark for early acral lentiginous
      melanoma, it may be observed in a limited number of benign entities, including
      subcorneal haematoma.

PMID- 20695870
TI  - 35 year-old man with falcine tumor.
AB  - A 35-year-old man presented with one month history of vomitus, dizziness and
      headache. CT and MR imaging revealed a 3.5 x 3.2 cm solitary extra-axial midline
      mass arising from the frontal falx cerebri; radiological findings were diagnostic
      of meningioma of the falx. At surgery, the tumour appeared as an extra-axial
      lesion and was removed via a left midline frontal craniotomy. Macroscopically,
      the surgical specimen was whitish, soft, well circumscribed and measured 1.6 cm
      in diameter; microscopic features showed a neoplasm with high cellularity,
      presence of mitotic figures, without necrosis or microvascular proliferation; the
      neoplasm was reactive for glial fibrillary acidic protein and MIB-1 index was
      about 15%. Given the localization, microscopic features were diagnostic of
      primary intracranial solitary leptomeningeal astrocytoma (PLA), WHO grade 3. PLA
      is a very rare lesion that arises in the leptomeninges of the brain or spinal
      cord with no involvement of intraparenchymatous tissue. Fifteen cases of PLA are
      reported in the literature. Retrospective neuroradiological analysis of this case
      failed to detect any findings to help in the differential diagnosis, thus
      confirming the fundamental role of the neuropathologist even in what can firstly
      appear to be a straightforward radiological diagnosis.

PMID- 20695871
TI  - "Posterior fossa lesion 45 years after ocular trauma".
AB  - We describe a patient who developed an isolated brain metastasis four years after
      his right eye was treated for conjunctival melanoma by excision and local
      chemotherapy. He had a history of ipsilateral ocular trauma by coal stuff while
      working in a mining industry. Conjunctival melanoma represents only 1.6% of all
      non-cutaneous melanoma. Metastasis of this kind of neoplasm to brain is a rare
      event, especially without evidence of prior or concurrent regional lymph node
      involvement.

PMID- 20695872
TI  - Quality of life and psychological distress in patients with Peutz-Jeghers
      syndrome.
AB  - Little is known about psychological distress and quality of life (QoL) in
      patients with Peutz-Jeghers syndrome (PJS), a rare hereditary disorder. We aimed
      to assess QoL and psychological distress in PJS patients compared to the general
      population, and to evaluate determinants of QoL and psychological distress in a
      cross-sectional study. PJS patients completed a questionnaire on QoL,
      psychological distress, and illness perceptions. The questionnaire was returned
      by 52 patients (85% response rate, 56% females, median age 44.5 years). PJS
      patients reported similar anxiety (p = 0.57) and depression (p = 0.61) scores as
      the general population. They reported a lower general health perception (p =
      0.003), more limitations due to emotional problems (p = 0.045) and a lower mental
      well-being (p = 0.036). Strong beliefs in negative consequences of PJS on daily
      life, a relapsing course of the disease, strong emotional reactions to PJS, and
      female gender were major determinants for a lower QoL. PJS patients experience a
      similar level of psychological distress as the general population, but a poorer
      general health perception, more limitations due to emotional problems, and a
      poorer mental QoL. Illness perceptions and female gender were major predictors
      for this lower QoL. These results may help to recognize PJS patients who might
      benefit from psychological support.

PMID- 20695873
TI  - Unexpected combination of inherited chorea-acanthocytosis with MDR3 (ABCB4)
      defect mimicking Wilson's disease.

PMID- 20695874
TI  - Lesch-Nyhan syndrome: a novel complex mutation with severe phenotype.

PMID- 20695878
TI  - Time-series analyses of Monterey Bay coastal microbial picoplankton using a
      'genome proxy' microarray.
AB  - To investigate the temporal, spatial and phylogenetic resolution of marine
      microbial community structure and variability, we designed and expanded a genome
      proxy array (an oligonucleotide microarray targeting marine microbial genome
      fragments and genomes), evaluated it against metagenomic sequencing, and applied
      it to time-series samples from the Monterey Bay. The expanded array targeted 268
      microbial genotypes across much of the known diversity of cultured and uncultured
      marine microbes. The target abundances measured by the array were highly
      correlated to pyrosequence-based abundances (linear regression R(2) = 0.85-0.91,
      P < 0.0001). Fifty-seven samples from ~4 years in Monterey Bay were examined with
      the array, spanning the photic zone (0 m), the base of the surface mixed layer
      (30 m) and the subphotic zone (200 m). A significant portion of the expanded
      genome proxy array's targets showed signal (95 out of 268 targets present in >= 1
      sample). The multi-year community survey showed the consistent presence of a core
      group of common and abundant targeted taxa at each depth in Monterey Bay, higher
      variability among shallow than deep samples, and episodic occurrences of more
      transient marine genotypes. The abundance of the most dominant genotypes peaked
      after strong episodic upwelling events. The genome-proxy array's ability to track
      populations of closely related genotypes indicated population shifts within
      several abundant target taxa, with specific populations in some cases clustering
      by depth or oceanographic season. Although 51 cultivated organisms were targeted
      (representing 19% of the array) the majority of targets detected and of total
      target signal (85% and ~92% respectively) were from uncultivated genotypes, often
      those derived from Monterey Bay. The array provided a relatively cost-effective
      approach (~$15 per array) for surveying the natural history of uncultivated
      lineages.

PMID- 20695882
TI  - The versatility of HDL: a crucial anti-inflammatory regulator.
AB  - BACKGROUND: Low levels of plasma high-density lipoprotein (HDL) represent a major
      cardiovascular risk factor and therefore raising HDL has been proposed to
      positively affect patients with atherosclerotic heart disease. However, the
      current evidence that raising HDL per se will reduce atherosclerosis and thereby
      cardiovascular events still remains controversial. AIMS: In this review, we
      discuss the diverse anti-atherogenic and anti-inflammatory properties of HDL in
      the light of recent findings indicating that the quality rather than the mere
      quantity of HDL determines its beneficial effects against atherosclerosis. More
      specifically, we will focus on the conspicuous anti-inflammatory properties of
      HDL as this might contribute to the overall beneficial effects of HDL in diseased
      patients such as modulation of costimulatory/adhesion molecule expression,
      cytokine production and inhibition of the prototypical proinflammatory
      transcription factor NF-kappaB. RESULTS: A range of clinical disorders share
      permanent inflammation as a characteristic hallmark including coronary artery
      disease, chronic kidney disease, diabetes mellitus or rheumatoid arthritis and
      also display distinct qualitative changes in the HDL compartment. Loss of anti
      inflammatory functions of HDL is emerging as an important risk factor for disease
      progression and survival in these clinical entities. CONCLUSIONS: It will be
      important to define the anti-inflammatory effects of HDL at the molecular level
      and to dissect the manifold functional implications to develop both novel
      functional assays that enable meaningful outcome studies and foster new
      therapeutic concepts in patients with altered HDL function.

PMID- 20695883
TI  - CCL18 in peritoneal dialysis patients and encapsulating peritoneal sclerosis.
AB  - BACKGROUND: Peritoneal fibrosis manifests clinically as membrane failure or
      encapsulating peritoneal sclerosis (EPS). There are no clinical or biochemical
      tests to determine the rate of progression of peritoneal fibrosis.
      CCL18/pulmonary and activation-regulated chemokine (PARC) is profibrotic and
      stimulates collagen production independent of the effect of transforming growth
      factor beta. This has not been studied in peritoneal dialysis (PD) patients.
      MATERIALS AND METHODS: We have prospectively studied 106 patients, free from
      infection/recent peritonitis. A high concentration of CCL18 was discovered by
      multiplex antibody arrays and quantified by ELISA. Serum and dialysate levels
      were examined for their prognostic values. RESULTS: By multiple regression
      analysis, dialysate CCL18 (6.76 +/- 0.66 MUg 4 h-1) correlated with increasing
      membrane transport status (TS) (P < 0.0001) and total glucose exposure/24 h (P =
      0.033). Serum CCL18 correlated with high TS (P = 0.0001) and duration of PD (P =
      0.001). After 12 months of follow-up, 57 patients remained on PD while 12
      patients were transferred to haemodialysis (HD) and seven developed EPS. Patients
      who subsequently developed EPS had higher baseline dialysate CCL18 (11.5 +/- 3.6
      MUg 4 h-1 vs. 5.6 +/- 0.82 MUg 4 h-1, P = 0.03) and serum CCL18 (156.9 +/- 12.8
      ng mL-1 vs. 124.8 +/- 12.2 ng mL-1, P = 0.02) compared with the stable PD group.
      CONCLUSION: This is the first report of high levels of CCL18 in the spent
      dialysate and serum from long-term PD patients. These levels correlated with
      dysfunction of peritoneal membrane transport status, therefore following CCL18 in
      a longitudinal study may be of interest.

PMID- 20695884
TI  - An atherogenic lipid profile with low serum paraoxonase-1 activity during
      nematode infection in rats.
AB  - BACKGROUND: Inflammation and oxidative stress are associated with cardiovascular
      diseases and underlying atherosclerosis. The high density lipoprotein (HDL)
      associated paraoxonase-1 (PON1) enzyme is known to be involved in the protection
      of serum lipids from such oxidation. Nonetheless, the disturbances of lipid
      profile during nematode-infected model have not yet been studied. Therefore, we
      aimed to explore the effects of Nippostrongylus brasiliensis infection in male
      Wistar rats, a model of human gastrointestinal nematode infections, on hepatic
      PON1 synthesis and the levels of lipid parameters. MATERIALS AND METHODS:
      Nippostrongylus brasiliensis-infected rats fed standard and high-fat diets. Serum
      paraoxonase and arylesterase activities were measured on day 0, 2, 4, 7, and 14
      post-infection (PI). Hepatic PONs and pro-inflammatory cytokines mRNA expression
      levels were evaluated in a standard diet-fed groups, and the disturbances in
      lipid profile as well as the levels of thiobarbituric acid reactive species
      (TBARS) and oxidized-LDL (Ox-LDL) were measured in high-fat diet-fed groups.
      RESULTS: We found that N. brasiliensis-infected rats fed the standard diet show a
      significant reduction in serum PON1 activity and down-regulation of hepatic PON1
      mRNA expression as well as up-regulation of hepatic IL-1beta, IL-beta receptor
      (R), TNF-alpha, and TNFR1 mRNA expressions in association with hepatic
      recruitments of Kupffer cells and neutrohils. In the presence of the high-fat
      diet, N. brasiliensis infection increases serum triglycerides, total cholesterol,
      LDL/VLDL, TBARS and Ox-LDL as well as decreases serum HDL coinciding with a
      maximum serum PON1 reduction. CONCLUSIONS: Nippostrongylus brasiliensis infection
      can induce atherogenic lipid profile and reduce serum PON1 activity.

PMID- 20695885
TI  - Gene expression signature is shared by patients with Alzheimer's disease and
      schizophrenia at the superior temporal gyrus.
AB  - BACKGROUND: Alzheimer's disease and Schizophrenia are two common diseases of the
      brain with significant differences in neuropathology, etiology and symptoms. This
      dissimilarity in the two diseases makes a comparison of the two ideal for
      detecting molecular substrates that are common to brain disorders in general.
      METHODS: In this study, we compared gene expression profiles across multiple
      brain areas, taken postmortem from patients with well-characterized Alzheimer's
      disease and Schizophrenia, and from cognitively normal control group with no
      neuro- or psychopathology. RESULTS: Although the totality of gene expression
      changes in the two diseases is dissimilar, a subset of genes appears to play a
      role in both diseases in specific brain regions. We find at Brodmann area 22, the
      superior temporal gyrus, a statistically significant number of genes with
      apparently disregulated expression in both diseases. Furthermore, we found genes
      that differentiate the two diseases from the control across multiple brain
      regions, and note that these genes were usually down-regulated. Brodmann area 8,
      part of the superior frontal cortex, is relatively abundant with them.
      CONCLUSION: We show overwhelming statistical evidence for Alzheimer's and
      Schizophrenia sharing a specific molecular background at the superior temporal
      gyrus. We suggest that impairment of the regulation of autophagy pathway is
      shared, in BA 22, by the two diseases.

PMID- 20695886
TI  - Ruling out subarachnoid hemorrhage.

PMID- 20695887
TI  - Amprenavir complexes with HIV-1 protease and its drug-resistant mutants altering
      hydrophobic clusters.
AB  - The structural and kinetic effects of amprenavir (APV), a clinical HIV protease
      (PR) inhibitor, were analyzed with wild-type enzyme and mutants with single
      substitutions of V32I, I50V, I54V, I54M, I84V and L90M that are common in drug
      resistance. Crystal structures of the APV complexes at resolutions of 1.02-1.85 A
      reveal the structural changes due to the mutations. Substitution of the larger
      side chains in PR(V32I) , PR(I54M) and PR(L90M) resulted in the formation of new
      hydrophobic contacts with flap residues, residues 79 and 80, and Asp25,
      respectively. Mutation to smaller side chains eliminated hydrophobic interactions
      in the PR(I50V) and PR(I54V) structures. The PR(I84V)-APV complex had lost
      hydrophobic contacts with APV, the PR(V32I)-APV complex showed increased
      hydrophobic contacts within the hydrophobic cluster and the PR(I50V) complex had
      weaker polar and hydrophobic interactions with APV. The observed structural
      changes in PR(I84V)-APV, PR(V32I)-APV and PR(I50V)-APV were related to their
      reduced inhibition by APV of six-, 10- and 30-fold, respectively, relative to
      wild-type PR. The APV complexes were compared with the corresponding saquinavir
      complexes. The PR dimers had distinct rearrangements of the flaps and 80's loops
      that adapt to the different P1' groups of the inhibitors, while maintaining
      contacts within the hydrophobic cluster. These small changes in the loops and
      weak internal interactions produce the different patterns of resistant mutations
      for the two drugs.

PMID- 20695889
TI  - Tumor suppressor p16 INK4a: Downregulation of galectin-3, an endogenous
      competitor of the pro-anoikis effector galectin-1, in a pancreatic carcinoma
      model.
AB  - The tumor suppressor p16(INK4a) has functions beyond cell-cycle control via
      cyclin-dependent kinases. A coordinated remodeling of N- and O-glycosylation, and
      an increase in the presentation of the endogenous lectin galectin-1 sensing these
      changes on the surface of p16(INK4a)-expressing pancreatic carcinoma cells (Capan
      1), lead to potent pro-anoikis signals. We show that the p16(INK4a)-dependent
      impact on growth-regulatory lectins is not limited to galectin-1, but also
      concerns galectin-3. By monitoring its expression in relation to p16(INK4a)
      status, as well as running anoikis assays with galectin-3 and cell transfectants
      with up- or downregulated lectin expression, a negative correlation between
      anoikis and the presence of this lectin was established. Nuclear run-off and
      northern blotting experiments revealed an effect of the presence of p16(INK4a) on
      steady-state levels of galectin-3-specific mRNA that differed from decreasing the
      transcriptional rate. On the cell surface, galectin-3 interferes with galectin-1,
      which initiates signaling toward its pro-anoikis activity via caspase-8
      activation. The detected opposite effects of p16(INK4a) at the levels of growth
      regulatory galectins-1 and -3 shift the status markedly towards the galectin-1
      dependent pro-anoikis activity. A previously undescribed orchestrated fine-tuning
      of this effector system by a tumor suppressor is discovered.

PMID- 20695888
TI  - Angiogenin prevents serum withdrawal-induced apoptosis of P19 embryonal carcinoma
      cells.
AB  - Angiogenin is a 14 kDa protein originally identified as an angiogenic protein.
      Recent development has shown that angiogenin acts on both endothelial cells and
      neuronal cells. Loss-of-function mutations in the coding region of the ANG gene
      have recently been identified in patients with amyotrophic lateral sclerosis.
      Angiogenin has been shown to control motor neuron survival and protect neurons
      from apoptosis under various stress conditions. In this article, we characterize
      the anti-apoptotic activity of angiogenin in pluripotent P19 mouse embryonal
      carcinoma cells. Angiogenin prevents serum withdrawal-induced apoptosis.
      Angiogenin upregulates anti-apoptotic genes, including Bag1, Bcl-2, Hells, Nf
      kappab and Ripk1, and downregulates pro-apoptotic genes, such as Bak1, Tnf, Tnfr,
      Traf1 and Trp63. Knockdown of Bcl-2 largely abolishes the anti-apoptotic activity
      of angiogenin, whereas the inhibition of Nf-kappab activity results in a partial,
      but significant, inhibition of the protective activity of angiogenin. Thus,
      angiogenin prevents stress-induced cell death through both the Bcl-2 and Nf
      kappab pathways.

PMID- 20695890
TI  - Annual variation of Microcystis genotypes and their potential toxicity in water
      and sediment from a eutrophic reservoir.
AB  - The relative genetic diversity of microcystin-producing Microcystis in the water
      and sediment of the Daechung Reservoir, Korea, was investigated over an entire
      year, including the cyanobacterial bloom season. The cells of potentially toxic
      Microcystis strains containing mcyJ genotypes and cells containing the genus
      specific cpcBA gene were quantified by a real-time PCR. The ratio of cells with
      mcyJ genotypes to the total Microcystis population in the water body was the
      highest (68.3%) in August when the cyanobacterial bloom reached its peak and the
      microcystin concentration in the water began to increase. A denaturing gradient
      gel electrophoresis profile analysis of the mcyJ genotypes performed to monitor
      any changes in the toxic Microcystis population showed the appearance of new
      genotypes and the disappearance of existing genotypes in the reservoir water
      collected during the summer months, when compared with the profile for the
      samples collected in spring and autumn. However, very little change was observed
      over the course of the year as regards the population diversity of the sediment
      samples.

PMID- 20695891
TI  - Bacterial community characterization and dynamics of indigo fermentation.
AB  - Indigo fermentation has been traditionally performed for dyeing textiles in
      Japan. Limited information is available on the microbiota involved and the
      succession of the bacterial community structure during indigo reduction. We
      investigated the bacterial community structure associated with indigo
      fermentation using denaturing gradient gel electrophoresis and clone library
      analyses of a PCR-amplified 16S rRNA gene in the early phase of fermentation
      carried out in our laboratory. A marked substitution of Halomonas spp. by
      Amphibacillus spp. was observed corresponding to the marked change in the state
      of indigo reduction. Although the reported indigo-reducing bacteria,
      Alkalibacterium spp., were not predominant in the early phase of fermentation,
      they were predominant in fermentation liquor aged for 10 months obtained from
      Date City, Japan, as determined by culture-dependent and culture-independent
      analyses. Novel indigo-reducing strains, Amphibacillus spp. strain C40 and
      Oceanobacillus spp. strain A21, were isolated from fermentation liquor aged for
      10 months and from liquor aged for 4 days, respectively. It is considered that,
      in addition to the strains belonging to the genus Alkalibacterium, strains
      belonging to genera Amphibacillus and Oceanobacillus play important roles in
      sustaining the reduced state of indigo during fermentation.

PMID- 20695892
TI  - Characterization of a bacterial community from a Northeast Siberian seacoast
      permafrost sample.
AB  - A combination of culture-dependent and -independent techniques was used to
      characterize a bacterial community, examine cold adaptation of isocitrate lyase
      (icl) genes, and detect genes with important ecological functions in a permafrost
      sample from the Bykovsky Peninsula on the Laptev Sea coast of northeast Siberia.
      According to the 16S rRNA gene sequence, 47 of the cultured isolates were members
      of the phyla Firmicutes, Proteobacteria, and Actinobacteria, with 85% of the
      isolates belonging to the genera Arthrobacter and Planococcus. The 16S rRNA gene
      clone library derived from DNA from the same permafrost sample contained
      sequences from the same phyla plus a few from Acidobacteria, but favored the
      Firmicutes at the cost of the Actinobacteria. A partial sequence of the icl gene,
      a proposed marker for cold adaptation, was determined for 25 isolates that grew
      at 0  degrees C. Two Psychrobacter isolates contained two of the four residues
      shown to be important for low-temperature activity in Colwellia maris or
      Colwellia psychrerythreaea. The presence in the permafrost DNA of genes with
      ecosystem functions was determined using geochip 2.0. The highest number of genes
      identified was from the categories of aromatic and natural polymer degradation
      genes, perhaps reflecting selection for the use of tundra vegetation-produced
      carbon.

PMID- 20695893
TI  - Microbial degradation of tetrachloromethane: mechanisms and perspectives for
      bioremediation.
AB  - Toxic man-made compounds released into the environment represent potential
      nutrients for bacteria, and microorganisms growing with such compounds as carbon
      and energy sources can be used to clean up polluted sites. However, in some
      instances, microorganisms contribute to contaminant degradation without any
      apparent benefit for themselves. Such cometabolism plays an important part in
      bioremediation, but is often difficult to control. Microbial degradation of
      tetrachloromethane (carbon tetrachloride, CCl(4)), a toxic ozone-depleting
      organic solvent mainly of anthropogenic origin, is only known to occur by
      cometabolic reduction under anoxic conditions. Yet no microbial system capable of
      using CCl(4) as the sole carbon source has been described. Microbial growth based
      on CCl(4) as a terminal electron acceptor has not been reported, although
      corresponding degradation pathways would yield sufficient energy. Known modes for
      the biodegradation of CCl(4) involve several microbial metabolites, mainly metal
      bound coenzymes and siderophores, which are produced by facultative or strictly
      anaerobic bacteria and methanogenic Archaea. Recent reports have demonstrated
      that CCl(4) dechlorination rates are enhanced by redox-active organic compounds
      such as humic acids and quinones, which act as shuttles between electron
      providing microorganisms and CCl(4) as a strong electron acceptor. The key
      factors underlying dechlorination of CCl(4), the practical aspects and specific
      requirements for microorganism-associated degradation of CCl(4) at contaminated
      sites and perspectives for future developments are discussed.

PMID- 20695894
TI  - Genome-wide sequencing data reveals virulence factors implicated in banana
      Xanthomonas wilt.
AB  - Banana Xanthomonas wilt is a newly emerging disease that is currently threatening
      the livelihoods of millions of farmers in East Africa. The causative agent is
      Xanthomonas campestris pathovar musacearum (Xcm), but previous work suggests that
      this pathogen is much more closely related to species Xanthomonas vasicola than
      to X. campestris. We have generated draft genome sequences for a banana
      pathogenic strain of Xcm isolated in Uganda and for a very closely related strain
      of X. vasicola pathovar vasculorum, originally isolated from sugarcane, that is
      nonpathogenic on banana. The draft sequences revealed overlapping but distinct
      repertoires of candidate virulence effectors in the two strains. Both strains
      encode homologues of the Pseudomonas syringae effectors HopW, HopAF1 and RipT
      from Ralstonia solanacearum. The banana-pathogenic and non-banana-pathogenic
      strains also differed with respect to lipopolysaccharide synthesis and type-IV
      pili, and in at least several thousand single-nucleotide polymorphisms in the
      core conserved genome. We found evidence of horizontal transfer between X.
      vasicola and very distantly related bacteria, including members of other
      divisions of the Proteobacteria. The availability of these draft genomes will be
      an invaluable tool for further studies aimed at understanding and combating this
      important disease.

PMID- 20695895
TI  - Response of Desulfovibrio vulgaris Hildenborough to hydrogen peroxide: enzymatic
      and transcriptional analyses.
AB  - We studied the effect of hydrogen peroxide (H(2)O(2)) stress on the anaerobic
      sulfate-reducing bacterium Desulfovibrio vulgaris Hildenborough. In a
      lactate/sulfate medium, growth was affected from 0.1 mM H(2)O(2) and totally
      inhibited at 0.7 mM. Surprisingly, transcript analyses revealed that the PerR
      regulon exhibited opposite regulation in the presence of 0.1 and 0.3 mM H(2)O(2).
      The variations in peroxidase- and superoxide dismutase-specific activities in the
      cell-free extracts of H(2)O(2)-stressed cultures were related to changes in the
      corresponding transcript abundance. Our data suggest that sod, sor, ngr and tpx
      genes, in addition to the PerR regulon, belong to the H(2)O(2) stimulon.

PMID- 20695896
TI  - Chemotactic factors of Flavobacterium columnare to skin mucus of healthy channel
      catfish (Ictalurus punctatus).
AB  - To gain an insight into the chemotactic factors involved in chemotaxis, we
      exposed a virulent strain of Flavobacterium columnare to various treatments,
      followed by analysis of its chemotactic activity. The chemotactic activity of F.
      columnare was significantly (P<0.05) inhibited when cells were pretreated by
      sodium metaperiodate, and a major portion of the capsular layer surrounding the
      cells was removed. Pretreatment of F. columnare with D-mannose, D-glucose and N
      acteyl-D-glucosamine significantly (P<0.05) inhibited its chemotaxis activity,
      whereas pretreatment of cells with d-fructose, L-fucose, D-glucosamine, d
      galactosamine, D-sucrose and N-acetyl-D-galactosamine failed to inhibit its
      chemotactic activity. These results indicate that at least three carbohydrate
      binding receptors (D-mannose, D-glucose and N-acteyl-D-glucosamine) associated
      with the capsule of F. columnare might be involved in the chemotactic responses.
      The relative transcriptional levels of three gliding motility genes (gldB, gldC,
      gldH) of F. columnare compared with 16S rRNA gene following the exposure of F.
      columnare to catfish skin mucus were evaluated by quantitative PCR (qPCR). qPCR
      results revealed that the transcriptional level of gldH was significantly
      (P<0.001) upregulated in normal F. columnare at 5 min postexposure to the catfish
      mucus. However, when F. columnare were pretreated with D-mannose, there was no
      upregulation of gliding motility genes. Taken together, our results suggest that
      carbohydrate-binding receptors play important roles in the chemotactic response
      to catfish mucus.

PMID- 20695897
TI  - Identification of a novel Porphyromonas gingivalis outer membrane protein, PG534,
      required for the production of active gingipains.
AB  - Gingipains are secreted endopeptidases important for the virulence and
      proliferation of Porphyromonas gingivalis; however, their secretion and
      biogenesis process is not yet fully elucidated. The PG0534 gene of P. gingivalis
      W83 encodes a novel protein, PG534, of unknown function. In a PG0534 deletion
      mutant 83K25, the activities of Arg-gingipains (RgpA and RgpB) and Lys-gingipain
      (Kgp) were reduced to 4-22% of those of the wild-type W83, while the activities
      of secreted exopeptidases DPPIV, DPP-7, and PTP-A were unaffected. This indicates
      that PG534 is required for the gingipain activity. Immunoblot analysis using anti
      Rgp or anti-Kgp antiserum showed that abnormal forms of gingipains were detected
      in the extracellular fraction from 83K25, suggesting that 83K25 exhibits
      dysfunctional gingipain secretory activity. Normal carbohydrate biogenesis of
      lipopolysaccharide is required for production of the active gingipains; however,
      lipopolysaccharide was not deficient in 83K25. Subcellular fractionation and
      immunoblot analysis using anti-PG534 antiserum localized PG534 to the outer
      membrane. In conclusion, we identified PG534 as a novel outer membrane protein
      required for the biogenesis of gingipains.

PMID- 20695898
TI  - Identification of candidate proteins for the diagnosis of Bartonella henselae
      infections using an immunoproteomic approach.
AB  - Bartonella henselae is an emerging gram-negative facultative intracellular
      pathogen transmitted via Ctenocephalides felis (cat fleas) or cat scratches.
      Bartonellosis is present mainly in the form of cat scratch disease (CSD),
      bacillary angiomatosis and infective endocarditis (IE). The methods used to
      diagnose B. henselae rely on culturing, immunofluorescent assays and molecular
      techniques. The objective of the present study was to identify candidate proteins
      for the serodiagnosis of bartonellosis with the differential discrimination of
      both clinical scenarios: CSD and IE. For this, an immunoproteomic approach
      combined with 2-DE, immunoblotting and matrix-assisted laser
      desorption/ionization time-of-flight MS has been developed. Immunoproteomic
      profiles of sera collected from patients with CSD and IE were compared with those
      of blood donors. We identified several candidate proteins as phage-encoding Pap31
      protein and an outer membrane protein of BH11510 that, in our view, might be
      useful for the serodiagnosis of bartonellosis.

PMID- 20695899
TI  - Is the abundance of Faecalibacterium prausnitzii relevant to Crohn's disease?
AB  - Reports that bacteria within the Firmicutes phylum, especially the species
      Faecalibacterium prausnitzii, are less abundant in Crohn's disease (CD) patients
      and supernatants from cultures of this bacterium are anti-inflammatory prompted
      the investigation of the possible correlations between the abundance of F.
      prausnitzii and the response to treatment in patients with gut diseases and
      healthy controls. In a randomized, double-blind trial, faeces were collected from
      healthy volunteers, and from patients with active CD, ulcerative colitis (UC) and
      irritable bowel syndrome before and after treatment. The levels of F. prausnitzii
      DNA in faecal suspensions were determined by PCR. Treatment by an elemental diet
      was effective, resulting in decreases in both the Harvey and Bradshaw index
      (P<0.001) and the concentrations of serum C-reactive protein (P<0.05). The total
      levels of F. prausnitzii in faecal samples from CD patients at presentation were
      lower than those in the other groups both before and after the treatment. There
      was no correlation between F. prausnitzii abundance and the severity of CD before
      treatment. Clinical improvement unexpectedly correlated with a significant
      decrease in the abundance of F. prausnitzii, especially the A2-165 subgroup
      (P<0.05). Our data suggest that a paucity of F. prausnitzii in the
      gastrointestinal microbial communities is likely to be a minor aetiological
      factor in CD: recovery following elemental diet is attributed to lower levels of
      gut flora.

PMID- 20695900
TI  - The F plasmid transfer activator TraJ is a dimeric helix-turn-helix DNA-binding
      protein.
AB  - TraJ is an activator of the transfer (tra) operon in the F plasmid that
      counteracts H-NS silencing at the main transfer promoter (P(Y)). TraJ contains
      226 aa (26 670 kDa), not 229 aa as reported previously, and forms homodimers.
      TraJ binds DNA containing P(Y)in vivo as demonstrated using a chromatin
      immunoprecipitation assay. Mutations within a predicted helix-turn-helix DNA
      binding motif reduced binding and decreased mating efficiency. The deletion of
      four or more residues from the C-terminus of TraJ blocked its activity, but did
      not interfere with DNA binding. This feature, as well as homology to the C
      terminal region of RovA and SlyA within the MarR/SlyA family, suggests that TraJ
      might counteract H-NS repression via a mechanism similar to these desilencing
      proteins.

PMID- 20695901
TI  - Diversity and applications of Bacillus bacteriocins.
AB  - Members of the genus Bacillus are known to produce a wide arsenal of
      antimicrobial substances, including peptide and lipopeptide antibiotics, and
      bacteriocins. Many of the Bacillus bacteriocins belong to the lantibiotics, a
      category of post-translationally modified peptides widely disseminated among
      different bacterial clades. Lantibiotics are among the best-characterized
      antimicrobial peptides at the levels of peptide structure, genetic determinants
      and biosynthesis mechanisms. Members of the genus Bacillus also produce many
      other nonmodified bacteriocins, some of which resemble the pediocin-like
      bacteriocins of the lactic acid bacteria (LAB), while others show completely
      novel peptide sequences. Bacillus bacteriocins are increasingly becoming more
      important due to their sometimes broader spectra of inhibition (as compared with
      most LAB bacteriocins), which may include Gram-negative bacteria, yeasts or
      fungi, in addition to Gram-positive species, some of which are known to be
      pathogenic to humans and/or animals. The present review provides a general
      overview of Bacillus bacteriocins, including primary structure, biochemical and
      genetic characterization, classification and potential applications in food
      preservation as natural preservatives and in human and animal health as
      alternatives to conventional antibiotics. Furthermore, it addresses their
      environmental applications, such as bioprotection against the pre- and post
      harvest decay of vegetables, or as plant growth promoters.

PMID- 20695902
TI  - Fibronectin: a multidomain host adhesin targeted by bacterial fibronectin-binding
      proteins.
AB  - Fibronectin, a large and essential multidomain glycoprotein, with multiple
      adhesive properties, functioning as a key link between cells and their
      extracellular matrices, is now recognized to be the target for a large number of
      bacterial proteins, which are generally considered to function as bacterial
      adhesins. In the last decade, an avalanche of bacterial fibronectin-binding
      proteins (FnBPs) has been identified, and the bioinformatics, structural biology,
      biological function and role in the virulence of a growing number of both Gram
      positive and Gram-negative proteins have begun to emerge. The evidence suggests
      that fibronectin has a wider biological remit than was previously thought and
      that bacterial FnBPs have actions over and above that of simple adhesion. This
      article provides an update on our current understanding of FnBPs from both Gram
      negative and Gram-positive bacteria and their proposed roles in bacterial
      colonization, bacterial virulence and bacteria-host interactions.

PMID- 20695903
TI  - Interaction of integrin alpha(6)beta(4) with ErbB3 and implication in heregulin
      induced ErbB3/ErbB2-mediated DNA synthesis.
AB  - Integrin alpha(6)beta(4) is abundantly expressed in normal epithelial cells and
      forms hemidesmosomes, one of cell-extracellular matrix junctions. In many types
      of cancer cells, integrin alpha(6)beta(4) is up-regulated, laminin, an integrin
      alpha(6)beta(4)-binding extracellular matrix protein, is cleaved, and
      hemidesmosomes are disrupted, eventually causing an enhancement of cancer cell
      movement and a facilitation of their invasion. It was previously shown that
      integrin alpha(6)beta(4) interacts with ErbB1 and ErbB2 and enhances cell
      proliferation and motility. Here we show that integrin alpha(6)beta(4) interacts
      with ErbB3 but not with ErbB1, ErbB2 or ErbB4, and enhances the heregulin
      induced, ErbB3/ErbB2 heterodimer-mediated DNA synthesis, but not cell motility,
      in A549 cells.

PMID- 20695904
TI  - Structural basis of protein disulfide bond generation in the cell.
AB  - The formation of protein disulfide bonds is an oxidative reaction that is crucial
      for the folding and maturation of many secreted and membrane proteins. Both
      prokaryotic and eukaryotic cells possess various disulfide oxidoreductases and
      redox-active cofactors to accelerate this oxidative reaction in a correct manner.
      Crystal or solution structures have been solved for some of the oxidoreductases
      in the past 10 years, leading to remarkable progress in the field of thiol-based
      redox cell biology. Consequently, structural and mechanistic similarities in the
      disulfide bond formation pathways have been uncovered. This review highlights the
      molecular basis of the elaborate oxidative systems operating in the Escherichia
      coli periplasm, the endoplasmic reticulum lumen and the mitochondrial
      intermembrane space. The accumulated knowledge provides important insights into
      how protein and redox homeostasis are maintained in the cell.

PMID- 20695905
TI  - Evidence that cleavage factor Im is a heterotetrameric protein complex
      controlling alternative polyadenylation.
AB  - Recent estimates indicate that approximately 60% of human genes include
      alternative polyadenylation sites. Hence, control of alternative polyadenylation
      can have a great impact on gene expression and cellular function. Cleavage factor
      (CF) Im is a 3'-end processing factor that is essential for in vitro processing.
      CFIm purified from HeLa cells is associated with three polypeptides of 25, 59 and
      68 kD, and it is generally thought to be a heterodimer composed of the 25-kD
      subunit and one of the larger subunits. Previously, we serendipitously discovered
      that knockdown of CFIm25 causes an upstream shift in the utilization of
      alternative polyadenylation sites. Here, we investigated whether this is because
      of an inherent property of the CFIm complex and, if so, what structural elements
      are important for its function. The major conclusions of this study are that (i)
      contrary to previous assumptions, CFIm forms stable heterotetramers through
      dimerization of CFIm25 and (ii) the CFIm complex per se is responsible for the
      control of alternative polyadenylation. (iii) However, the structurally related
      CFIm68 and CFIm59 are functionally redundant and (iv) CFIm68 appears to have a
      higher specific activity. Thus, this study establishes that CFIm not only plays a
      general role in 3'-end processing but also plays a regulatory role in poly(A)
      site selection.

PMID- 20695906
TI  - Efficacy and safety of metformin for treatment of type 2 diabetes in elderly
      Japanese patients.
AB  - AIM: The maximum dosage of metformin allowed for clinical use in Japan is much
      less than half that in Western countries, making it difficult to apply the
      results of clinical trials in Western countries to Japanese patients. In
      particular, the efficacy and safety of metformin in elderly patients are largely
      unknown. METHODS: Among 1508 patients who were newly prescribed metformin at our
      hospital from 2000-2006, patients with sufficient clinical data were
      retrospectively studied for the safety (n=1132) and efficacy (n=568) of the drug.
      Of 568 patients in whom the efficacy of metformin was analyzed, 180 patients
      (31.7%) were elderly, aged 65 years or over. RESULTS: Metformin was effective for
      the treatment of type 2 diabetes in Japanese patients, with significant
      improvement in HbA1c level at all time-points after 1 month, with the largest
      decrease by approximately 0.9% in patients treated with 750 mg/day and
      approximately 0.7% in those treated with 500 mg/day, at 4 months. Metformin
      improved glycemic control in elderly patients as well as non-elderly patients.
      The efficacy was independent of age, sex, degree of obesity and concomitant use
      of other drugs. No significant difference was observed in elevated lactic acid
      levels between elderly and non-elderly patients. No case of lactic acidosis was
      observed. CONCLUSIONS: These results suggest that the efficacy of metformin in
      Japanese elderly patients with type 2 diabetes is not different from that in non
      elderly patients, and that its safety might be linked to specific and well
      documented contraindications rather than age itself.

PMID- 20695907
TI  - Registry of inherited bleeding disorders in Poland--current status and potential
      role of the HemoRec database.
AB  - We present data collected in HemoRec, an Internet-based platform implemented in
      2006 in 15 haemophilia treatment centres in Poland and compare them with the
      national registry of inherited bleeding disorders established since 1991 at the
      Institute of Haematology and Blood Transfusion in Warsaw. We also analyse the
      current status of haemophilia treatment in Poland as well as future perspectives.
      Data on 1102 patients registered in HemoRec were analysed and compared with 4294
      patients in the national registry (status as at 17.08.2009). The number of
      patients with severe haemophilia, mild/moderate haemophilia and von Willebrand in
      HemoRec is 530, 328 and 54 (respectively), compared with 1199, 1167 and 1128 in
      the national registry. The mean age of all haemophilic patients registered in
      HemoRec is 26.2 years, compared with 37.3 years in the general Polish male
      population in 2008. The number of haemophilic patients with inhibitor registered
      in HemoRec is 102 compared with 155 in the national registry (resulting in a
      prevalence of 14.9% of all severe haemophilia A and 1.6% of all severe
      haemophilia B patients). HemoRec includes data on a representative group of
      Polish haemophilic patients, mostly with haemophilia and haemophilia with
      inhibitor. von Willebrand's disease is largely under-registered in Poland. The
      survival of Polish haemophilic patients is shorter than that in the general
      population. The number of inhibitor patients in Poland is relatively large and
      should be decreased by wider availability of immunotolerance induction in 2010.

PMID- 20695908
TI  - Successful mitral valve repair in a patient with factor V deficiency.

PMID- 20695909
TI  - FIX mutation spectrum in haemophilia B patients from Jordan: identification of
      three novel mutations.

PMID- 20695911
TI  - Health Services Research in 2020: data and methods needs for the future.

PMID- 20695910
TI  - Congenital afibrinogenaemia in pregnancy.

PMID- 20695921
TI  - Liver transplant pathology - messages for the non-specialist.
AB  - This review, based on a presentation at the BDIAP meeting in London 2008, aims to
      guide histopathologists working outside transplant centres in the differential
      diagnosis of late post transplant liver biopsies. It focuses on the histological
      patterns of the late post transplant complications - autoimmune hepatitis, acute
      and chronic rejection, recurrent viral hepatitis, and biliary disease. Analysis
      of the character and distribution of inflammatory infiltrate, bile duct changes,
      and fibrosis by the histopathologist must then be set within the clinical context
      to arrive at the most appropriate diagnosis. For this reason, review of the
      biopsy at the transplant centre is recommended. In a broader context, the
      tabulation of diagnostic features in chronic inflammatory liver diseases produced
      by the Banff Working Group can, with the exception of rejection, usefully be
      applied outside the transplant setting.

PMID- 20695922
TI  - Transcriptional profiling of Anopheles gambiae  mosquitoes for adult age
      estimation.
AB  - The age distribution of female mosquitoes in the field is a critical component of
      vectorial capacity because of the extrinsic incubation period of mosquito-borne
      pathogens. However this parameter has not been well characterized in malaria
      vectors because of methodological difficulties; transcriptional profiling
      provides a potential new approach for age determination. In Anopheles gambiae,
      microarrays were used to examine global gene expression over adult life. Nine
      genes were selected from the 2714 gene transcripts that displayed age-related
      transcription patterns, and quantitative reverse transcription PCR used to select
      the four best performing genes. The resulting age estimation assay was able to
      predict female age from lab-reared samples with sufficient accuracy to provide a
      potentially useful tool for studies of malaria epidemiology and control.

PMID- 20695923
TI  - Heterochromatin marks HP1gamma, HP1alpha and H3K9me3, and DNA damage response
      activation in human testis development and germ cell tumours.
AB  - Heterochromatinization has been implicated in fundamental biological and
      pathological processes including differentiation, senescence, ageing and
      tumourigenesis; however, little is known about its regulation and roles in human
      cells and tissues in vivo. Here, we show distinct cell-type- and cancer-stage
      associated patterns of key heterochromatin marks: histone H3 trimethylated at
      lysine 9 (H3K9me3) and heterochromatic adaptor proteins HP1alpha and HP1gamma,
      compared with the gammaH2AX marker of endogenously activated DNA damage response
      (DDR) and proliferation markers in normal human foetal (n=4) and adult (n=29)
      testes, pre-invasive carcinoma in situ (CIS; n=26) lesions and a series of overt
      germ cell tumours, including seminomas (n=26), embryonal carcinomas (n=18) and
      teratomas (n=11). Among striking findings were high levels of HP1gamma in foetal
      gonocytes, CIS and seminomas; enhanced multimarker heterochromatinization without
      DDR activation in CIS; and enhanced HP1alpha in teratoma structures with
      epithelial and neuronal differentiation. Differential expression of the three
      heterochromatin markers suggests their partly non-overlapping roles, and
      separation of heterochromatinization from DDR activation highlights distinct
      responses of germ cells vs. somatic tissues in early tumourigenesis. Conceptually
      interesting findings were that subsets of human cells in vivo proliferate despite
      enhanced heterochromatinization, and that cells can strongly express even
      multiple heterochromatin features in the absence of functional retinoblastoma
      protein and without DDR activation. Overall, these results provide novel insights
      into cell-related and tumour-related diversity of heterochromatin in human
      tissues in vivo, relevant for andrology and intrinsic anti-tumour defence roles
      attributed to activated DDR and cellular senescence.

PMID- 20695924
TI  - Correlation between testicular sperm extraction outcomes and clinical, endocrine
      and testicular histology parameters in 120 azoospermic men with normal serum FSH
      levels.
AB  - We retrospectively evaluated the clinical and hormonal profiles, sperm extraction
      outcomes and testicular histology parameters in 120 azoospermic men with normal
      serum follicle-stimulating hormone (FSH) level. Microsurgical epididymal sperm
      aspiration (MESA) and testicular sperm extraction (TESE) were performed in 33 and
      87 cases, respectively. Sperm were successfully retrieved in all the MESA
      procedures and in 65 of the TESE procedures. The mean serum FSH and inhibin B
      levels and the testicular volume differed significantly according to whether or
      not sperm were retrieved. The threshold serum inhibin B value for predicting
      successful TESE was 123.5pg/mL (sensitivity: 69.7%; specificity: 66.7%). The 13
      patients with Sertoli cell only syndrome (SCOS) had a higher mean serum FSH level
      and a lower mean serum inhibin B level than the other phenotypes. TESE was
      negative for 11 of the 13 SCOS men. The mean+/-SD inhibin B level was
      significantly lower in patients with 5-10IU/L of FSH than those with 2-5IU/L of
      FSH (108.30+/-53.86 vs. 175.23+/-70.17pg/mL, respectively). The sperm retrieval
      rates were 71.42% for the group with 5-10IU/L of FSH and 87.32% for the group
      with 2-5IU/L of FSH. Ten of the 13 SCOS men had a FSH level between 5 and 10IU/L.
      The clinical pregnancy rate was significantly lower (p=0.04) in the group with 5
      10IU/L (50%) of FSH than in the group with 2-5IU/L (77.5%) of FSH. In conclusion,
      there is no FSH value below which spermatogenesis is always found. Inhibin B
      assays and clinical assessments are thus of particular value in men with normal
      serum FSH levels.

PMID- 20695929
TI  - Two-year predictive validity of conduct disorder subtypes in early adolescence: a
      latent class analysis of a Canadian longitudinal sample.
AB  - BACKGROUND: Investigating the latent structure of conduct disorder (CD) can help
      clarify how symptoms related to aggression, property destruction, theft, and
      serious violations of rules cluster in individuals with this disorder.
      Discovering homogeneous subtypes can be useful for etiologic, treatment, and
      prevention purposes depending on the qualitative or quantitative nature of the
      symptomatology. The aim of the present study is twofold: identify subtypes of CD
      in young adolescents based on latent class analysis (LCA) and investigate the two
      year predictive validity of CD subtypes on deviant and criminal lifestyles.
      METHODS: Adolescent-reported CD symptoms were collected using the National
      Longitudinal Survey of Children and Youth. Three cohorts of 12-13-year-olds were
      assessed during 1994-1995, 1996-1997, and 1998-1999 (N = 4,125). RESULTS: Latent
      class analyses yielded 4 distinct subtypes: No CD (82.4%); Non-Aggressive CD
      ('NACD', 13.9%); Physically Aggressive CD ('PACD', 2.3%); and Severe-Mixed CD
      ('SMCD', 1.4%). Predictive validity at age 14-15 was non-specific, although the
      SMCD type had, by far, the highest odds of deviant and criminal lifestyle
      outcomes in comparison to youth with PACD or NACD. NACD and PACD had similar odds
      of deviant outcomes, even if most NACD youth were subthreshold CD (fewer than
      three symptoms). CONCLUSION: In early adolescence, CD is qualitatively and
      quantitatively heterogeneous, suggesting multiple developmental pathways.
      However, they appear to predict similarly violent and non-violent outcomes.

PMID- 20695930
TI  - Anxious attachment style and salivary cortisol dysregulation in healthy female
      children and adolescents.
AB  - BACKGROUND: Attachment style has been linked with basal cortisol secretion in
      healthy adult women. We investigated whether dysregulation in basal cortisol
      secretion may be evident in younger healthy females. METHODS: Sixty healthy
      females aged 9-18 years (mean 14.16, SD +/- 2.63 years) participated in the
      Attachment Style Interview (ASI). Eight saliva samples, synchronised to
      awakening, were collected per day on two consecutive weekdays to examine the
      cortisol awakening response (CAR) and the subsequent diurnal decline. RESULTS:
      Participants exhibiting an anxious attachment style had higher cortisol levels on
      awakening, in contrast to those who were securely attached. The anxious insecure
      group also showed an attenuated CAR compared to all other participants.
      Attachment style groups did not differ in cortisol secretion over the remainder
      of the day. CONCLUSIONS: These findings indicate that the same pattern of
      cortisol dysregulation associated with disorder in adulthood manifests as a
      function of anxious (but not avoidant) insecure attachment style in females
      during healthy childhood and adolescence.

PMID- 20695931
TI  - Combination antihypertensive treatment: is initiation order important?

PMID- 20695932
TI  - Professors: the world is not flat.

PMID- 20695933
TI  - Predictors of hypertension control in a diverse general cardiology practice.
AB  - Factors influencing hypertension (HTN) control in the United States are not well
      understood. The authors utilized a newly designed survey instrument to interview
      patients presenting to a diverse, general cardiology practice at a tertiary care
      center in order to identify factors associated with HTN control. The study was
      completed in 154 participants, and 121 (78.6%) had HTN. Of those, 111 (91.7%) had
      awareness of HTN, and 72 (59.5%) had HTN control, defined as <140/90 mm Hg. In a
      multivariate analysis, race/ethnicity was not associated with HTN control, but
      private insurance (odds ratio [OR] 3.40, 95% confidence interval [CI] 1.25-9.28),
      nonsmoker status (OR 4.36, CI 1.22-15.51), and number of medications used (OR
      1.32, CI 1.12-1.56) were associated with HTN control. Correct recognition of
      systolic blood pressure goal and knowledge of one's current state of HTN control
      were also associated with control. In conclusion, in a general cardiology
      practice where patients had a high degree of healthcare access, race/ethnicity
      was not associated with HTN control, while type of insurance, nonsmoker status,
      and increased number of medications used were associated. In addition, 2 novel
      predictors of HTN control, recognition of systolic blood pressure goal and
      knowledge of HTN control, were identified that can be utilized in creating new
      HTN treatment interventions.

PMID- 20695934
TI  - Masked hypertension defined by ambulatory blood pressure monitoring is associated
      with an increased serum glucose level and urinary albumin-creatinine ratio.
AB  - The authors evaluated the relationship of hypertensive target organ damage to
      masked hypertension assessed by ambulatory blood pressure (BP) and home blood
      pressure (HBP) monitoring in 129 participants without taking antihypertensive
      medication. Masked hypertension was defined as office BP < or =140/90 mm Hg and
      24-hour ambulatory BP > or =130/80 mm Hg. The masked hypertensive participants
      defined by 24-hour ambulatory BP (n=13) had a higher serum glucose level (126 vs
      96 mg/dL, P=.001) and urinary albumin-creatinine ratio (38.0 vs 7.5 mg/gCr,
      P<.001) than the normotensive participants (n=74); however, these relationships
      were not observed when the authors defined groups using HBP (> or =135/85 mm Hg).
      Masked hypertension by both 24-hour ambulatory BP and HBP had a higher urinary
      albumin-creatinine ratio than normotension by both 24-hour ambulatory BP and HBP
      (62.1 vs 7.4 mg/gCr, P=.001), and than masked hypertension by HBP alone (9.3
      mg/gCr, P=.009). Masked hypertension defined by 24-hour ambulatory BP is
      associated with an increased serum glucose level and urinary albumin-creatinine
      ratio, but these relationships are not observed in masked hypertension defined by
      HBP.

PMID- 20695935
TI  - Performance of two metabolic syndrome definitions in the estimation of
      cardiovascular disease among hypertensive patients.
AB  - The authors evaluated the significance of metabolic syndrome (MetS) diagnosis, as
      defined by the National Cholesterol Education Program (NCEP) and by the
      International Diabetes Federation (IDF), in the evaluation of cardiovascular risk
      in hypertensive patients. Among 638 patients, the prevalence of MetS was 54.7%
      when the IDF criteria were used, compared with 45.5% when the NCEP criteria were
      used. MetS correlated significantly with the presence of cardiovascular disease
      (CVD). In patients without type 2 diabetes mellitus (T2DM), only MetS diagnosed
      using the IDF criteria was associated with the presence of CVD. In those with
      T2DM, MetS was not associated with CVD, regardless of the criteria used. The
      diagnosis of MetS, using either set of criteria, was associated with the
      development of T2DM. We conclude that, in hypertensive patients without diabetes,
      a diagnosis of MetS according to IDF criteria, but not the NCEP criteria, is
      useful in identifying individuals with a higher probability of incident CVD. In
      patients with diabetes, a population already considered at high risk for CVD, a
      diagnosis of MetS, regardless of the criteria used, has no further impact on
      prognosis.

PMID- 20695936
TI  - Urine albumin excretion, within normal range, reflects increasing prevalence of
      metabolic syndrome in patients with essential hypertension.
AB  - Microalbuminuria is a prognostic marker of cardiovascular disease and is related
      to metabolic syndrome (MetS). For this purpose, the authors examined the
      relationship of low grade albuminuria to MetS, using 4 current definitions and a
      MetS score. They studied 6650 consecutive, nondiabetic, hypertensive patients
      with normal microalbumin excretion. MetS was defined by Adult Treatment Panel
      III, American Heart Association, World Heart Organization, International Diabetes
      Federation criteria, and MetS Gruppo Italiano per lo Studio della Streptochinasi
      nell'Infarcto Miocardico (GISSI) score. Urine microalbumin concentration was
      measured after a 24-hour urine collection by immunonephelometry. By all
      definitions, hypertensive patients with MetS had higher microalbumin levels.
      Significantly higher microalbumin levels were observed as the number of metabolic
      components rose. After adjustment for systolic blood pressure, the strength of
      this association was reduced to a nonsignificant level. Microalbumin levels,
      within normal range, are increased in patients with MetS, irrespective of the
      definition criteria.

PMID- 20695937
TI  - Hypertension treatment and control among 28 physician practices across the United
      States: results of the Hypertension: Assessment of Treatment to Target (HATT)
      Study.
AB  - Chart reviews were conducted at 28 US physician practices to evaluate blood
      pressure (BP) management. The cross-sectional study included 8250 adult patients
      diagnosed with hypertension. The primary outcome variable was BP control (BP
      <140/90 mm Hg for nondiabetic and <130/80 mm Hg for diabetic patients). Mean body
      mass index was 30.9 kg/m(2), 49% were obese, 54% were women, mean age was 64.9
      years, and 25% had diabetes. Mean BP was 132.2/77.8 mm Hg, and 55.8% of study
      participants had controlled BP. Patients with uncontrolled BP were more likely to
      be obese or African American, and more than twice as likely to have diabetes.
      Almost 1 in 5 nondiabetic patients (18%), and 38% of diabetic patients, were
      above goal BP by >10 mm Hg systolic or >5 mm Hg diastolic; among these patients,
      36% used 0 or 1 antihypertensive medication, and 32% used 2 medications.
      Opportunity exists to improve BP control in this population.

PMID- 20695938
TI  - Risk of pregnancy-related hypertension within 5 years of exposure to drinking
      water contaminated with Escherichia coli O157:H7.
AB  - The authors evaluated the risk for pregnancy-related hypertension among
      previously healthy women who conceived within 5 years of exposure to drinking
      water contaminated with Escherichia coli O157.H7 in Walkerton, Canada (2000).
      Chronic hypertension was defined as systolic/diastolic blood pressure >/=140/90
      mm Hg before 20 weeks gestation; gestational hypertension was defined as new
      onset systolic/diastolic blood pressure >/=140/90 mm Hg >/=20 weeks gestation.
      The incidence of hypertension was compared between women who were asymptomatic
      during the outbreak to those who experienced acute gastroenteritis. Blood
      pressure data were available for 135 of 148 eligible pregnancies. The adjusted
      relative risks for chronic and gestational hypertension were 1.5 (95% confidence
      interval [CI]: 0.3-7.7) and 1.0 (95% CI: 0.4-2.5), respectively. Mean arterial
      pressure before 20 weeks gestation was 2.7 mm Hg higher in women who had acute
      gastroenteritis (95% CI: 0.05-5.4). A trend toward higher chronic hypertension
      and mean arterial pressure in early pregnancy was observed among women who
      experienced gastroenteritis after exposure to bacterially-contaminated drinking
      water.

PMID- 20695939
TI  - Reevaluating the use of antihypertensive medications, a first step toward
      reducing polypharmacy in very old patients.

PMID- 20695940
TI  - How significant is white coat hypertension?

PMID- 20695941
TI  - Review of recent literature: Existing kidney disease classification guideline
      needs to incorporate degree of proteinuria with estimated glomerular filtration
      rate to more accurately predict cardiovascular and renal risk.

PMID- 20695942
TI  - Leadership message. Forging ahead into the new healthcare frontier.

PMID- 20695944
TI  - Continuous metabolic syndrome risk score, body mass index percentile, and leisure
      time physical activity in American children.
AB  - The objective of this study was to determine independent and joint association of
      body mass index (BMI) percentile and leisure time physical activity (LTPA) with
      continuous metabolic syndrome (cMetS) risk score in 12- to 17-year-old American
      children. The 2003 to 2004 US National Health and Nutrition Examination Survey
      data were used for this investigation. LTPA was determined by self-report. cMetS
      risk score was calculated using standardized residuals of arterial blood
      pressure, triglycerides, glucose, waist circumference, and high-density
      lipoprotein cholesterol. Multiple linear regression analysis was used to evaluate
      association of BMI percentile and LTPA with cMetS risk score, adjusting for
      confounders. Increased BMI percentile and LTPA were each associated with
      increased and decreased cMetS risk score, respectively ((P<.01). There was a
      gradient of increasing cMetS risk score by BMI percentile cutpoints, from healthy
      weight (-0.77) to overweight (3.43) and obesity (6.40) ((P<.05). A gradient of
      decreasing cMetS risk score from sedentary (0.88) to moderate (0.17) and vigorous
      (-0.42) LTPA levels was also observed (P<.01). The result of this study suggests
      that promoting LTPA at all levels of weight status may help to reverse the
      increasing trends of metabolic syndrome in US children.

PMID- 20695945
TI  - Inter- and intra-ethnic group comparison of metabolic syndrome components among
      morbidly obese adolescents.
AB  - This study explored inter- (between) and intra- (within) ethnic group differences
      in metabolic syndrome components among a clinical sample of morbidly obese (body
      mass index [BMI] > or =97th percentile for age and sex) 12- to 18-year-olds
      originating from Latin America and the Caribbean Basin and a matched
      (age/ethnicity/sex/BMI percentile) national sample (N=208, both samples) of
      Mexican American and non-Hispanic blacks from the 1999 to 2006 National Health
      and Nutrition Examination Survey (NHANES). Mexican American and non-Hispanic
      black boys from the NHANES/national sample had significantly higher mean fasting
      glucose levels compared with Latin and Caribbean blacks (98.50 vs 85.42 mg/dL,
      97.34 vs 86.44 mg/dL, respectively, (P< .001 for both comparisons). Conversely,
      both diastolic/systolic blood pressure was consistently higher among
      Latin/Caribbean adolescents vs Mexican American and non-Hispanic blacks for all
      age/sex/ethnic groups. These results indicate that morbidly obese adolescents
      from both major ethnic groups and subgroups within these groups show health
      related comorbidities in both clinic- and population-based settings.

PMID- 20695946
TI  - Raised plasma urotensin II in type 2 diabetes patients is associated with the
      metabolic syndrome phenotype.
AB  - Urotensin II (UII) exerts multiple effects on the cardiovascular system, acts as
      a diabetogenic agent, and may also contribute to the development of the metabolic
      syndrome (MetS). The aim of this study was to determine circulating UII in
      patients with type 2 diabetes mellitus (T2DM) and its relationship with MetS. A
      total of 360 consecutive patients with T2DM were included. MetS presence/absence
      (MetS [+]/[-]) was defined according to American Heart Association/National
      Heart, Lung and Blood Institute criteria. Plasma concentrations of UII were
      determined by radioimmunoassay. UII levels were significantly higher in MetS (+)
      than in MetS (-) T2DM patients (0.97 pg/mL [0.93-1.01], n=294 vs 0.82 pg/mL [0.75
      0.88] pg/mL, n=66, respectively; P<.001). Multiple logistic regression analysis
      showed that UII was significantly associated with MetS (+) (odds ratio, 6.41 [95%
      confidence interval, 1.21-16.04]; P=.02). UII plasma concentrations are
      significantly higher in T2DM patients presenting with MetS. Therefore,
      circulating UII may participate in the worsening course of some T2DM patients and
      may provide novel therapeutic perspectives.

PMID- 20695947
TI  - Latching onto life: living in the area of tension between the possibility of life
      and the necessity of death.
AB  - AIM: To present one of the findings from a large-scale hermeneutic research
      project focusing on promoting a deeper understanding of health and suffering
      because of serious cancer disease. BACKGROUND: Although suffering is a main
      concern for caring science, there is limited research focusing on the suffering
      of the patients with a serious cancer disease from the patients' perspective and
      few studies focusing on the patient's health resources and the dialectic between
      these. DESIGN: The study has a hermeneutic design inspired by Gadamer's
      ontological hermeneutics. METHOD: Fifteen Norwegian patients with cancer disease
      were interviewed. They were informed about the seriousness of their situation and
      that there was no more curative treatment to offer. RESULTS: The results show
      that the patients lived their lives in a dialectic oscillation, a struggle
      between health and suffering. They expressed health through striving towards
      normal life, aspiring for hope, taking responsibility for their own life and
      experiencing belongingness with their next of kin. Suffering was expressed
      through experiences of bodily aversion, uncertainty and fear of the future,
      sorrow and needs, anxiety, despair and loneliness. The patients were lonely in
      this struggle, as conversations about existence and death did not occur, neither
      with the nurses nor with their next of kin. Death remained veiled in silence.
      CONCLUSIONS: In confronting one's own death, there seems to be striving for
      health, striving for wholeness and for becoming a self in a life dominated by
      suffering. Becoming a self implies a desire to be a responsible human being and
      to experience integrity and dignity in life despite increasing dependency on
      others. RELEVANCE TO CLINICAL PRACTICE: There seems to be a great need in
      clinical practice to give priority to, and increase, the consciousness and
      competence of nurses to see and respond to the spiritual/existential concerns of
      patients with a serious cancer disease.

PMID- 20695948
TI  - Aromatherapy for treatment of hypertension: a systematic review.
AB  - OBJECTIVES: The objective of this review is to systematically review the evidence
      for the effectiveness of aromatherapy in the treatment of high blood pressure.
      METHODS: Twelve databases were searched from their inception through December
      2009. Controlled trials testing aromatherapy in patients with hypertension of any
      origin that assessed blood pressure were considered. The selection of studies,
      data extraction and validations were performed independently by two reviewers.
      RESULTS: One randomized clinical trial (RCT) and four non-randomized controlled
      clinical trials (CCTs) met our inclusion criteria. The one RCT included tested
      the effects of aromatherapy as compared with placebo and showed significant
      reduction of systolic blood pressure and diastolic blood pressure. All of the
      four CCTs showed favourable effects of aromatherapy. However, all of the CCTs
      also had a high risk of bias. CONCLUSION: The existing trial evidence does not
      show convincingly that aromatherapy is effective for hypertension. Future studies
      should be of high quality with a particular emphasis on designing an adequate
      control intervention.

PMID- 20695949
TI  - The impact of physicians' reactions to uncertainty on patients' decision
      satisfaction.
AB  - RATIONALE: Patients' and physicians' response to uncertainty may affect decision
      outcomes. The purpose of this study was to explore the impact of patients' and
      physicians' reactions to uncertainty on patients' satisfaction with breast health
      decisions. METHODS: Seventy-five women facing breast cancer prevention or
      treatment decisions and five surgeons were recruited from a breast health centre.
      Patients' and physicians' anxiety from uncertainty was assessed using the
      Physicians' Reactions to Uncertainty Scale; wording was slightly modified for
      patients to ensure the scale was applicable. Patients' decision satisfaction was
      assessed 1-2 weeks after their appointment. A mixed-effects logistic regression
      model was used to assess associations between patients' and providers' anxiety
      from uncertainty and patients' decision satisfaction. A provider-specific random
      effects term was included in the model to account for correlation among patients
      treated by the same provider. RESULTS: Patients' decision satisfaction was
      associated with physicians' anxiety from uncertainty (beta = 0.92, P < 0.01), but
      not with patients' anxiety from uncertainty (beta = -0.18, P > 0.27).
      CONCLUSIONS: This study suggests that physicians' reactions to uncertainty may
      have an effect on decision satisfaction in patients. More research is needed to
      confirm this relationship and to determine how to help patient-provider dyads to
      manage the uncertainty that is inherent in most cancer decisions.

PMID- 20695950
TI  - Validating a conceptual model for an inter-professional approach to shared
      decision making: a mixed methods study.
AB  - RATIONALE, AIMS AND OBJECTIVES: Following increased interest in having inter
      professional (IP) health care teams engage patients in decision making, we
      developed a conceptual model for an IP approach to shared decision making (SDM)
      in primary care. We assessed the validity of the model with stakeholders in
      Canada. METHODS: In 15 individual interviews and 7 group interviews with 79
      stakeholders, we asked them to: (1) propose changes to the IP-SDM model; (2)
      identify barriers and facilitators to the model's implementation in clinical
      practice; and (3) assess the model using a theory appraisal questionnaire. We
      performed a thematic analysis of the transcripts and a descriptive analysis of
      the questionnaires. RESULTS: Stakeholders suggested placing the patient at its
      centre; extending the concept of family to include significant others; clarifying
      outcomes; highlighting the concept of time; merging the micro, meso and macro
      levels in one figure; and recognizing the influence of the environment and
      emotions. The most common barriers identified were time constraints, insufficient
      resources and an imbalance of power among health professionals. The most common
      facilitators were education and training in inter-professionalism and SDM,
      motivation to achieve an IP approach to SDM, and mutual knowledge and
      understanding of disciplinary roles. Most stakeholders considered that the
      concepts and relationships between the concepts were clear and rated the model as
      logical, testable, having clear schematic representation, and being relevant to
      inter-professional collaboration, SDM and primary care. CONCLUSIONS: Stakeholders
      validated the new IP-SDM model for primary care settings and proposed few
      modifications. Future research should assess if the model helps implement SDM in
      IP clinical practice.

PMID- 20695951
TI  - Significant event analysis: a comparative study of knowledge, process and
      attitudes in primary care.
AB  - INTRODUCTION: Significant event analysis (SEA) is now well established in UK
      primary care. Previously, considerable variation has been reported in the
      knowledge, skills and attitudes of general practitioners undertaking SEA. Little
      is known about the wider team's understanding, participation or perceptions. We
      therefore aimed to determine the awareness, degree of analysis and perceived risk
      of recurrence of a recent significant event, types of discussion forums, staff
      groups' participation and perceived barriers. Comparisons were made with a 2003
      survey and significant changes described. METHOD: A postal questionnaire survey
      was undertaken of a random selection of general practice team members in National
      Health Service Greater Glasgow in 2008/9. RESULTS: In total, 375/711 respondents
      (53%) from 111 practices participated. The vast majority was aware of a recent
      significant event, 29% reported not implementing a change and 23% perceived the
      risk of recurrence as moderate to high. Administrative and community-based staff
      were infrequently involved in meetings. Dedicated significant event meetings
      remain uncommon (P = 0.06). Perceptions improved since 2003, but lack of time
      remained a concern. DISCUSSION: This survey was the first known attempt to
      include all members of the primary care team while studying SEA. Awareness and
      analysis levels were high, but only lead to sustainable improvement of care
      quality and clinical safety if teams implement change. Greater use should be made
      of dedicated SEA meetings and participation of all staff groups increased to gain
      full benefits. Lack of time can be managed pragmatically by prioritizing events
      based on their perceived severity, potential for change and potential team
      involvement.

PMID- 20695952
TI  - How do patients choose their doctors for primary care in a free market?
AB  - AIMS: A recent trend in health care system is to provide more choices to the
      patients. This study surveyed the general public's choices for primary care in
      Hong Kong which has the setting of free choices for private or public service and
      also direct access to specialists. METHODS: We used a combined qualitative and
      quantitative approach. We held five focus group interviews with participants of
      different socio-economic categories. Information from the focus groups helped to
      design a questionnaire for random telephone interviews with members of the public
      aged 18 or above. RESULTS: There were 37 participants in the focus groups and
      1647 respondents in the telephone survey. The most important factor for choosing
      a doctor was proximity to home or workplace, followed by quick relief from the
      illness. Once continuity of care had been established, distance was of less
      importance but comprehensive care was valued. Nearly 70% of the public had
      regular doctors. About 93% of the public would consult specialists directly when
      they thought they needed a specialist's opinion. Nearly 30% chose specialists for
      any medical care and 38% preferred specialists to also look after their primary
      care problems. CONCLUSION: Convenient accessibility was the most important factor
      for the initial choice of primary care doctors by the general public. The
      perceived clinical proficiency of the doctor determined future continuity of
      care. Patients liked to have direct access to specialists. Though some chose to
      see the specialists even for primary care problems, most people had regular
      doctors who were likely to have the attributes of family doctors.

PMID- 20695953
TI  - Goal scaling for low back pain in primary care: development of a semi-structured
      interview incorporating minimal important change.
AB  - RATIONALE, AIMS AND OBJECTIVES: Goal attainment scaling was an individualized
      assessment technique developed to evaluate the provision of complex public
      services. However, this produced a measure which was driven more by the need to
      demonstrate clinical efficacy rather than reflecting a patient's own aspirations.
      People with low back pain have problems ranging from functional daily activities
      to areas which impinge upon their wider role in society and quality of life.
      Commonly used scales to measure back pain-related disability may not capture
      domains of relevance to patients. The aim of this project was to develop a goal
      based individualized assessment tool capable of defining meaningful change in
      condition from the patient perspective for use in longitudinal clinical studies.
      METHODS: We developed a semi-structured interview to elicit patient important
      goals. We refined our initial framework by conducting consecutive rounds of
      interviews with patients and reviewing the feedback. Within this approach, we
      included a point identified as the minimum level of change needed within each
      goal that would be considered a meaningful improvement in condition by the
      patient. RESULTS: Fifteen patients with low back pain took part in the study.
      Three rounds of interviews were held to refine the questions used to develop the
      goal scales. Overall, the participants identified a total of 59 problem areas,
      reducing these to the 45 most important goals (three for each patient). The
      minimal significant improvement was identified on 31 (69%) of these, with all
      except one patient able to identify this marker on two or more of their goal
      scales. CONCLUSIONS: The formation of individualized goal scales was successful
      in all of the participants in this study. Patients were able to understand the
      concept of 'minimal important change', and identify a specific target to reflect
      this for two-thirds of their chosen goals.

PMID- 20695954
TI  - Shifting stroke care from the hospital to the nursing home: explaining the
      outcomes of a Dutch case.
AB  - RATIONALE, AIMS AND OBJECTIVES: Supply chains can contribute to better care for
      stroke patients and more efficiency. However, such outcomes are hampered when
      links in the chain are weak. The article aims to further the knowledge about the
      causes and possible improvements of weak links thereby using theory about rules
      for action and routines (action patterns). METHOD: We executed a single case
      study of a chain of service delivery to stroke patients by a university hospital
      and a nursing home in the city of Maastricht, the Netherlands. Methods included
      document study, interviews, observations, process mapping, use of data matrices
      and performance of t-tests. RESULTS: In the case, the care delivery process in
      the chain was redesigned to improve the flow of patients and to reduce the length
      of hospital stay. Length of stay was reduced. However, transfer of patients from
      the hospital to the nursing home was hampered. At this weak link in the chain,
      the redesign clashed with the routines of hospital paramedics who did not want to
      work according to the redesign. CONCLUSIONS: The applied theory is useful to
      understand why a link in a supply chain is weak. Negotiations can be used to
      strengthen a link.

PMID- 20695955
TI  - A cost simulation for mammography examinations taking into account equipment
      failures and resource utilization characteristics.
AB  - OBJECTIVE: This work develops a cost analysis estimation for a mammography
      clinic, taking into account resource utilization and equipment failure rates.
      MATERIALS AND METHODS: Two standard clinic models were simulated, the first with
      one mammography equipment, two technicians and one doctor, and the second (based
      on an actually functioning clinic) with two equipments, three technicians and one
      doctor. Cost data and model parameters were obtained by direct measurements,
      literature reviews and other hospital data. A discrete-event simulation model was
      developed, in order to estimate the unit cost (total costs/number of examinations
      in a defined period) of mammography examinations at those clinics. The cost
      analysis considered simulated changes in resource utilization rates and in
      examination failure probabilities (failures on the image acquisition system). In
      addition, a sensitivity analysis was performed, taking into account changes in
      the probabilities of equipment failure types. RESULTS: For the two clinic
      configurations, the estimated mammography unit costs were, respectively, US$
      41.31 and US$ 53.46 in the absence of examination failures. As the examination
      failures increased up to 10% of total examinations, unit costs approached US$
      54.53 and US$ 53.95, respectively. The sensitivity analysis showed that type 3
      (the most serious) failure increases had a very large impact on the patient
      attendance, up to the point of actually making attendance unfeasible.
      CONCLUSIONS: Discrete-event simulation allowed for the definition of the more
      efficient clinic, contingent on the expected prevalence of resource utilization
      and equipment failures.

PMID- 20695956
TI  - Evaluation of communication assessment practices during the acute stages post
      stroke.
AB  - RATIONALE, AIMS AND OBJECTIVES: Early detection of communication impairment post
      stroke is an important prognostic indicator and promotes the use of
      individualized treatment protocols. Therefore, the methods for speech and
      language assessment used by communication experts in acute settings following
      stroke were investigated. METHODS: A survey was conducted among 254 speech and
      language pathologists providing acute care for patients following stroke in all
      states and territories across Australia and New Zealand. Respondent attitudes and
      practices in speech and language assessment post stroke were recorded with a
      standardized questionnaire collected online. RESULTS: A total of 174 (68.5%)
      speech and language pathologists responded. Over 70% of participants assessed
      language and 80% assessed speech using their own clinical assessments.
      Respondents identified limited test repeatability and poor sensitivity to change
      over acute periods as key areas of concern for currently available standardized
      assessments. CONCLUSIONS: Subjective and/or un-standardized assessments were the
      most commonly used measures of communication during the acute phases post stroke.
      These results highlight a critical need for the development of population
      specific communication assessments that build on existing clinician derived
      techniques and expertise while considering the acute time demands and transient
      nature of patient's communicative functioning.

PMID- 20695957
TI  - Community pharmacy dispensing of prescription medicine sample packs: changing the
      business of medicine initiation?

PMID- 20695958
TI  - Mental health services accreditation in Italy.
AB  - RATIONALE, AIMS AND OBJECTIVES: This paper deals mainly with health services peer
      accreditation in Italy, but a preliminary brief description of governmental
      accreditation is done, inasmuch as peer initiatives must take into account - and
      build upon - institutional accreditation requirements and practices. In Italy, no
      independent agency, such as the 'Commission for Health Improvement' or the
      'Health Advisory Service' is operating. METHODS: In the field of mental health
      services, two major peer accreditation programmes have been carried out. The
      paper focuses on the most original features of both programmes and reports
      examples of standards belonging to the more recent accreditation manual. RESULTS:
      In the manual, because of a lesser need to reach a consensus between services
      with widely different outlook, professional standards are more detailed and the
      importance that they should be based on the principle of evidence-based mental
      health is more stressed. CONCLUSIONS: The Italian peer accreditation approach in
      mental health may raise interest also in other countries.

PMID- 20695960
TI  - An EST-based genome scan using 454 sequencing in the marine snail Littorina
      saxatilis.
AB  - Genome scans have been used in the studies of ecological speciation to find
      genomic regions ('outlier loci') showing reduced gene flow between divergent
      populations/species. High-throughput sequencing ('454') offers new opportunities
      in this field via transcriptome sequencing. Divergent ecotypes of the marine
      gastropod Littorina saxatilis represent a good example of incipient ecological
      speciation. We performed a 454-based genome scan between H and M ecotypes of L.
      saxatilis from the British Isles using cDNA of pooled individuals. Allele
      frequencies were calculated for 2454 single nucleotide polymorphisms (SNPs),
      within 572 contigs, and 7% of loci were detected as outliers. Functional
      annotation of the contigs containing outlier SNPs showed that they included shell
      matrix and muscle proteins (lithostathine, mucin, titin), proteins involved in
      energetic metabolism (arginine kinase, NADH dehydrogenase) and reverse
      transcriptases. Follow-up investigations into these proteins and unannotated
      outliers will be a promising route in the study of ecological speciation in L.
      saxatilis.

PMID- 20695962
TI  - A phantom extinction? New insights into extinction dynamics of the Don-hare Lepus
      tanaiticus.
AB  - The Pleistocene to Holocene transition was accompanied by a worldwide extinction
      event affecting numerous mammalian species. Several species such as the woolly
      mammoth and the giant deer survived this extinction wave, only to go extinct a
      few thousand years later during the Holocene. Another example for such a Holocene
      extinction is the Don-hare, Lepus tanaiticus, which inhabited the Russian plains
      during the late glacial. After being slowly replaced by the extant mountain hare
      (Lepus timidus), it eventually went extinct during the middle Holocene. Here, we
      report the phylogenetic relationship of L. tanaiticus and L. timidus based on a
      339-basepair (bp) fragment of the mitochondrial D-loop. Phylogenetic tree- and
      network reconstructions do not support L. tanaiticus and L. timidus being
      different species. Rather, we suggest that the two taxa represent different
      morphotypes of a single species and the extinction of 'L. tanaiticus' represents
      the disappearance of a local morphotype rather than the extinction of a species.

PMID- 20695963
TI  - Resistance to environmental stress in Drosophila ananassae: latitudinal variation
      and adaptation among populations.
AB  - Geographical variation in traits related to fitness is often the result of
      adaptive evolution. Stress resistance traits in Drosophila often show clinal
      variation, suggesting that selection affects resistance traits either directly or
      indirectly. Multiple stress resistance traits were investigated in 45 natural
      populations of Drosophila ananassae collected from all over India. There was
      significant positive correlation between starvation resistance and lipid content.
      Significant negative correlations between desiccation and lipid content and
      between desiccation and heat resistance were also found. Flies from lower
      latitudes had higher starvation resistance, heat resistance and lipid content but
      the pattern was reversed for desiccation resistance. These results suggest that
      flies from different localities varied in their susceptibility to starvation
      because of difference in their propensity to store body lipid. Multiple
      regression analysis provided evidence of climatic selection driven by latitudinal
      variation in the seasonal amplitude of temperature and humidity changes within
      the Indian. Finally, our results suggest a high degree of variation in stress
      resistance at the population level in D. ananassae.

PMID- 20695964
TI  - Female Cape sugarbirds (Promerops cafer) modify egg investment both for extra
      pair mates and for male tail length.
AB  - The differential allocation hypothesis predicts that females should invest more
      in reproduction when paired with attractive males. We measured egg volume in Cape
      sugarbirds (Promerops cafer), a sexually dimorphic passerine, in relation to
      paternity of the offspring and in response to an experimental tail length
      treatment. We manipulated tail length, after pair formation, but before egg
      laying: males had their tails either shortened or left unmanipulated. Our
      manipulation was designed to affect female allocation in a particular breeding
      attempt rather than long-term mate choice: males with shortened tails would
      appear to be signalling at a lower level than they should given their quality. We
      found that egg volume was smaller in the nests of males with experimentally
      shortened tails but larger when the offspring were the result of extra-pair
      matings. Both these findings are consistent with the differential allocation
      hypothesis. We suggest that tail length may be used by females as a cue for mate
      quality, eliciting reduced female investment when breeding with social mates; and
      with males with shortened tails.

PMID- 20695965
TI  - Sexual conflict in wing size and shape in Drosophila melanogaster.
AB  - Intralocus sexual conflict occurs when opposing selection pressures operate on
      loci expressed in both sexes, constraining the evolution of sexual dimorphism and
      displacing one or both sexes from their optimum. We eliminated intralocus
      conflict in Drosophila melanogaster by limiting transmission of all major
      chromosomes to males, thereby allowing them to win the intersexual tug-of-war.
      Here, we show that this male-limited (ML) evolution treatment led to the
      evolution (in both sexes) of masculinized wing morphology, body size, growth
      rate, wing loading, and allometry. In addition to more male-like size and shape,
      ML evolution resulted in an increase in developmental stability for males.
      However, females expressing ML chromosomes were less developmentally stable,
      suggesting that being ontogenetically more male-like was disruptive to
      development. We suggest that sexual selection over size and shape of the imago
      may therefore explain the persistence of substantial genetic variation in these
      characters and the ontogenetic processes underlying them.

PMID- 20695966
TI  - Male territoriality and 'sex confusion' in recently adapted lizards at White
      Sands.
AB  - The evolution of intersexual interactions, like mate choice, during ecological
      speciation has received widespread attention. However, changes in intrasexual
      interactions, like male territoriality, during ecological divergence are largely
      unexamined. We conducted field experiments with adaptively diverged populations
      of the eastern fence lizard (Sceloporus undulatus) to determine whether
      territorial males behaved differently towards ecologically similar vs. dissimilar
      intruders. We performed trials with light-coloured males from White Sands, New
      Mexico and dark-coloured males from the surrounding desert. We found that
      intruders from White Sands elicited more aggression than intruders from dark-soil
      habitat. We also documented a case of 'sex confusion' where white-sand males
      courted dark-soil intruders. We found population differences in signalling patch
      size that can explain both aggression bias and sex misidentification. We argue
      that direct selection (for population recognition or optimal signal transmission)
      and indirect selection (by-products of ecological adaptation) should influence
      both intersexual and intrasexual interactions during ecological speciation.

PMID- 20695967
TI  - Pollinator-mediated selection in a specialized pollination system: matches and
      mismatches across populations.
AB  - Most studies on pollinator-mediated selection have been performed in generalized
      rather than specialized pollination systems. This situation has impeded
      evaluation of the extent to which selection acts on attraction or specialized key
      floral traits involved in the plant-pollinator phenotypic interphase. We studied
      pollinator-mediated selection in four populations of Nierembergia linariifolia, a
      self-incompatible and oil-secreting plant pollinated exclusively by oil
      collecting bees. We evaluated whether floral traits experience variable selection
      among populations and whether attraction and fit traits are heterogeneously
      selected across populations. Populations differed in every flower trait and
      selection was consistently observed for corolla size and flower shape, two traits
      involved in the first steps of the pollination process. However, we found no
      selection acting on mechanical-fit traits. The observation that selection
      occurred upon attraction rather than mechanical-fit traits, suggests that plants
      are not currently evolving fine-tuned morphological adaptations to local
      pollinators and that phenotypic matching is not necessarily an expected outcome
      in this specialized pollination system.

PMID- 20695968
TI  - Sex-specific selection on energy metabolism--selection coefficients for winter
      survival.
AB  - Selection for different fitness optima between sexes is supposed to operate on
      several traits. As fitness-related traits are often energetically costly,
      selection should also act directly on the energetics of individuals. However,
      efforts to examine the relationship between fitness and components of the energy
      budget are surprisingly scarce. We investigated the effects of basal metabolic
      rate (BMR, the minimum energy required for basic life functions) and body
      condition on long-term survival (8 winter months) with manipulated densities in
      enclosed populations of bank voles (Myodes glareolus). Here, we show that
      survival selection on BMR was clearly sex-specific but density-independent. Both
      the linear selection gradient and selection differential for BMR were positive in
      females, whereas survival did not correlate with male characteristics. Our
      findings emphasize the relative importance of individual physiology over
      ecological factors (e.g. intra-specific competition). Most current models of the
      origin of endothermy underline the importance of metabolic optima in females,
      whose physiology evolved to fulfil demands of parental provisioning in mammals.
      Our novel findings of sex-specific selection could be related to these life
      history differences between sexes.

PMID- 20695969
TI  - The purge of genetic load through restricted panmixia in a Drosophila experiment.
AB  - Using Drosophila melanogaster, we explore the consequences of restricted panmixia
      (RP) on the genetic load caused by segregating deleterious recessive alleles in a
      population where females mate a full sib with probability about (1/2) and mate
      randomly otherwise. We find that this breeding structure purges roughly half the
      load concealed in heterozygous condition. Furthermore, fitness did not increase
      after panmixia was restored, implying that, during RP, the excess of expressed
      load induced by inbreeding had also been efficiently purged. We find evidences
      for adaptation to laboratory conditions and to specific selective pressures
      imposed by the RP protocol. We discuss some of the consequences of these results,
      both for the evolution of population breeding structures and for the design of
      conservation programmes.

PMID- 20695970
TI  - Spatial seed and pollen games: dispersal, sex allocation, and the evolution of
      dioecy.
AB  - The evolutionary forces shaping within- and across-species variation in the
      investment in male and female sex function are still incompletely understood.
      Despite earlier suggestions that in plants the evolution or cosexuality vs.
      dioecy, as well as sex allocation among cosexuals, is affected by seed and pollen
      dispersal, no formal model has explicitly used dispersal distances to address
      this problem. Here, we present a game-theory model as well as a simulation study
      that fills in this gap. Our model predicts that dioecy should evolve if seeds and
      pollen disperse widely and that sex allocation among cosexuals should be biased
      towards whichever sex function produces more widely dispersing units. Dispersal
      limitations stabilize cosexuality by reinforcing competition between spatially
      clumped dispersal units from the same source, leading to saturating fitness
      returns that render sexual specialization unprofitable. However, limited pollen
      dispersal can also increase the risk of selfing, thus potentially selecting for
      dioecy as an outbreeding mechanism. Finally, we refute a recent claim that
      cosexuals should always invest equally in both sex functions.

PMID- 20695971
TI  - Population differentiation in the swordtail characin (Corynopoma riisei ): a role
      for sensory drive?
AB  - Sensory drive, where the efficacy of a sexual signal depends on the environment
      in which it is employed, is a potential mechanism behind divergent evolution of
      secondary sexual traits. Male swordtail characins are equipped with a narrow and
      transparent extension of the gill cover with a flag-like structure at its tip.
      This opercular flag mimics a prey item and is employed by males as a 'lure' to
      attract the attention of females during mating attempts. We conducted a study of
      genetic and morphological differentiation across swordtail characin populations
      throughout their native range in Trinidad. The morphology of the opercular flag
      varied across populations and several aspects of this variation match the
      predicted hallmarks of sensory drive. First, morphological differentiation of the
      flag across populations was unrelated to genetic similarity at neutral genetic
      markers. Second, the shape of the flag covaried with those aspects of body shape
      that should reflect adaptation to different feeding regimes. Third, and most
      importantly, the shape of the flag covaried across populations with those
      environmental characteristics that should most closely reflect differences in
      local prey abundance. Overall, our results are consistent with a scenario where
      the evolution of this male sexual signal tracks food-related shifts in female
      sensory biases across populations, thus providing at least provisional support
      for a role for sensory drive in population differentiation.

PMID- 20695972
TI  - How did the Great Auk raise its young?
AB  - The extant auks show three strategies of chick rearing--precocial (chicks leave
      the nest site when a few days old), intermediate (young raised to a mass of
      around 20% of adult mass) and semi-precocial (young raised to a mass of around
      65% of adult mass). It is not known which strategy the extinct Great Auk used. In
      this paper, we investigate this issue by a novel combination of a time and energy
      budget model and phylogenetic comparison. The first approach indicates that for
      reasonable estimates of the equation parameters, the Great Auk could have
      followed an intermediate strategy. For a limited range of parameters, the Great
      Auk could have followed the semi-precocial strategy. Phylogenetic comparison
      shows that it is unlikely that the Great Auk followed a precocial strategy. The
      results suggest that the Great Auk followed an intermediate strategy as does its
      presumed closest extant relative the Razorbill.

PMID- 20695973
TI  - Profiling protein expression and interactions: proximity ligation as a tool for
      personalized medicine.
AB  - The ability to detect very low levels of expressed proteins has enormous
      potential for early diagnostics and intervention at curable stages of disease. An
      extended range of targets such as interacting or post-translationally modified
      proteins can further improve the potential for diagnostics and patient
      stratification, and for monitoring response to treatment. These are critical
      building blocks for personalized treatment strategies to manage disease. The past
      few decades have seen a remarkably improved understanding of the molecular basis
      of disease in general, and of tumour formation and progression in particular.
      This accumulated knowledge creates opportunities to develop drugs that
      specifically target molecules or molecular complexes critical for survival and
      expansion of tumour cells. However, tumours are highly variable between patients,
      necessitating the development of diagnostic tools to individualize treatment
      through parallel analysis of sets of biomarkers. The proximity ligation assay
      (PLA) can address many of the requirements for advanced molecular analysis. The
      method builds on the principle that recognition of target proteins by two, three
      or more antibodies can bring in proximity DNA strands attached to the antibodies.
      The DNA strands can then participate in ligation reactions, giving rise to
      molecules that are amplified for highly sensitive detection. PLA is particularly
      well suited for sensitive, specific and multiplexed analysis of protein
      expression, post-translational modifications and protein-protein interactions.
      The analysis of this extended range of biomarkers will prove critical for the
      development and implementation of personalized medicine.

PMID- 20695974
TI  - Hemochromatosis, iron toxicity and disease.

PMID- 20695975
TI  - Chronic fatigue syndrome reflects loss of adaptability.

PMID- 20695976
TI  - Signal transduction of receptor-mediated antiproliferative action of melatonin on
      human prostate epithelial cells involves dual activation of Galpha(s) and
      Galpha(q) proteins.
AB  - Melatonin has been shown to inhibit the proliferation of malignant and
      transformed human prostate epithelial cells by transcriptional up-regulation of
      p27(Kip1) expression via MTNR1A receptor-mediated activation of protein kinase A
      (PKA) and protein kinase C (PKC) in parallel. Given that melatonin MTNR1A
      receptor is a G protein-coupled receptor, this study was conducted to identify
      the specific G proteins that mediate the antiproliferative action of melatonin on
      human prostate epithelial cells. In 22Rv1 and RWPE-1 cells, knockdown of either
      Galpha(s) or Galpha(q) , but not Galpha(i2) expression by RNA interference,
      abrogated the effects of melatonin on p27(Kip1) and cell proliferation.
      Conversely, cellular overexpression of activated mutants of Galpha(s) and
      Galpha(q) in 22Rv1 and RWPE-1 cells mimicked the effects of melatonin on prostate
      epithelial cell antiproliferation by increasing p27(Kip1) expression through
      downstream activation of PKA and PKC in parallel. Moreover, melatonin or 2
      iodomelatonin induced elevation of adenosine-3',5'-cyclic monophosphate (cAMP) in
      22Rv1 and RWPE-1 cells. The effects of 2-iodomelatonin on cAMP were blocked by
      the nonselective MTNR1A/MTNR1B receptor antagonist luzindole but were not
      affected by the selective MTNR1B receptor antagonist 4-phenyl-2
      propionamidotetraline (4-P-PDOT). Furthermore, knockdown of Galpha(s) mitigated
      the stimulatory effects of 2-iodomelatonin on cAMP. Collectively, the data
      demonstrated, for the first time, functional coupling of MTNR1A receptor to
      Galpha(s) in cancerous or transformed human cells expressing endogenous melatonin
      receptors. Our results also showed that dual activation of Galpha(s) and
      Galpha(q) proteins is involved in the signal transduction of MTNR1A receptor
      mediated antiproliferative action of melatonin on human prostate epithelial
      cells.

PMID- 20695977
TI  - rFVIIa transported from the blood stream into tissues is functionally active.

PMID- 20695978
TI  - Proplatelet formation deficit and megakaryocyte death contribute to
      thrombocytopenia in Myh9 knockout mice.
AB  - BACKGROUND:  Inactivation of the mouse Myh9 gene (Myh9Delta) or its mutation in
      MYH9-related diseases leads to macrothrombocytopenia. Paradoxically, previous
      studies using in vitro differentiated megakaryocytes showed an increased capacity
      for proplatelet formation when myosin was absent or inhibited. METHODS:  To
      explore the origin of the thrombocytopenia induced by myosin deficiency, we
      studied proplatelet formation using bone marrow explants of wild-type (WT) and
      Myh9Delta mouse where megakaryocytes have matured in their native environment.
      RESULTS AND DISCUSSION:  A dramatic decrease in the number and complexity of
      proplatelets was observed in megakaryocytes from Myh9Delta mice, while inhibition
      of myosin activity by blebbistatin increased proplatelet formation from WT mature
      megakaryocytes. Moreover, Myh9Delta megakaryocytes had a smaller size than the WT
      cells. These data indicate that myosin deficiency acts negatively on proplatelet
      formation, probably by impairing in situ megakaryocyte maturation, while myosin
      activity is dispensable at the latest stage of proplatelet formation. In
      addition, ultrastructural examination of Myh9Delta bone marrow revealed an
      increased proportion of megakaryocytes exhibiting signs of non-apoptotic cell
      death as compared with the WT mice. CONCLUSION:  These data indicate that
      thrombocytopenia in Myh9Delta mice results from defective development of
      megakaryocyte size, impaired proplatelet formation and increased cell death.

PMID- 20695979
TI  - The distal carboxyterminal domains of murine ADAMTS13 influence proteolysis of
      platelet-decorated VWF strings in vivo.
AB  - BACKGROUND: The multidomain metalloprotease ADAMTS13 regulates the size of von
      Willebrand factor (VWF) multimers upon their release from endothelial cells. How
      the different domains in ADAMTS13 control VWF proteolysis in vivo remains largely
      unidentified. METHODS: Seven C-terminally truncated murine ADAMTS13 (mADAMTS13)
      mutants were constructed and characterized in vitro. Their ability to cleave VWF
      strings in vivo was studied in the ADAMTS13(-/-) mouse. RESULTS: Murine MDTCS
      (devoid of T2-8 and CUB domains) retained full enzyme activity in vitro towards
      FRETS-VWF73 and the C-terminal T6-8 (del(T6-CUB)) and CUB domains (delCUB) are
      dispensable under these assay conditions. In addition, mADAMTS13 fragments
      without the spacer domain (MDT and M) had reduced catalytic efficiencies. Our
      results hence indicate that similar domains in murine and human ADAMTS13 are
      required for activity in vitro, supporting the use of mouse models to study
      ADAMTS13 function in vivo. Interestingly, using intravital microscopy we show
      that removal of the CUB domains abolishes proteolysis of platelet-decorated VWF
      strings in vivo. In addition, whereas MDTCS is fully active in vivo, partial
      (del(T6-CUB)) or complete (delCUB) addition of the T2-8 domains gradually
      attenuates its activity. CONCLUSIONS: Our data demonstrate that the ADAMTS13 CUB
      and T2-8 domains influence proteolysis of platelet-decorated VWF strings in vivo.

PMID- 20695980
TI  - Circulating microparticles in cardiovascular disease: implications for
      atherogenesis and atherothrombosis.
AB  - The complex and multifactorial nature of atherogenesis and development of
      atherothrombotic complications involves numerous interactions between various
      cell types inside the vascular wall (e.g. macrophages and smooth muscle cells)
      and in the blood (e.g. leukocytes and platelets). One relatively recent advance
      in this area is the discovery of circulating microparticles and their role in
      endothelial damage, platelet activation, hypercoagulability and regulation of
      inter-cellular interactions. Microparticles are small anucleoid phospholipid
      vesicles released from different cells, such as platelets, erythrocytes,
      leukocytes and endothelial cells. Microparticles carry surface proteins and
      include cytoplasmic material of the parental cells responsible for the exertion
      of microparticle-mediated biological effects. About 25% of the procoagulant
      activity of stimulated platelet suspensions is associated with microparticles
      released upon platelet activation and their surface may be approximately 50-100
      fold more procoagulant than the surface of activated platelets per se. The
      available lines of evidence indicate that shedding of microparticles from the
      parental cells is not just a passive process accompanying cellular dysfunction
      and apoptosis, but a tightly regulated mechanism implicated in the interactions
      between various cell types. The role of microparticles as biological messengers
      is supported by their differential and specific involvement in the
      pathophysiology of different cardiovascular disorders, including atherogenesis
      and thrombosis.

PMID- 20695981
TI  - CLEC-2 is not required for platelet aggregation at arteriolar shear.

PMID- 20695982
TI  - Thrombophilic mutations and cardiovascular disease: the case is still open.

PMID- 20695983
TI  - Is there really a relationship between the plasma concentration of the active
      metabolite of clopidogrel and the results of platelet function tests?

PMID- 20695984
TI  - Do not adjust the platelet count in light transmittance aggregometry when
      predicting thrombotic events after percutaneous coronary intervention.

PMID- 20695985
TI  - Usefulness of a flow cytometric analysis of intraplatelet vasodilator-stimulated
      phosphoprotein phosphorylation for the detection of patients with genetic defects
      of the platelet P2Y(12) receptor for ADP.

PMID- 20695986
TI  - Phase I clinical trial and pharmacokinetics of intravesical mitomycin C in dogs
      with localized transitional cell carcinoma of the urinary bladder.
AB  - BACKGROUND: Transitional cell carcinoma (TCC) is the most common cancer of the
      urinary tract in dogs. The most frequent cause of death is urinary obstruction
      from the primary tumor. Standard medical therapy for TCC is only partially
      effective. HYPOTHESIS/OBJECTIVES: Intravesical administration of mitomycin C
      (MMC) in dogs with invasive TCC will result in antitumor activity against the
      primary tumor and minimal systemic drug absorption. ANIMALS: Thirteen privately
      owned dogs with naturally occurring, histopathologically diagnosed TCC of the
      urinary bladder. METHODS: A prospective phase I trial was performed. MMC was
      given intravesically (600 MUg/mL initial concentration) for 1 h/d for 2
      consecutive days each month. The MMC concentration was escalated to a maximum of
      800 MUg/mL in groups of 3 dogs until the maximum tolerated dose (MTD) was
      determined. Serum assays for MMC were performed to determine the extent of
      systemic absorption of the MMC. RESULTS: The MTD of MMC based on local toxicoses
      was 700 MUg/mL (1-h dwell time, 2 consecutive days). In addition, 2 dogs had
      severe myelosuppression and appeared to have systemic absorption of MMC. Five
      dogs had partial remission, and 7 dogs had stable disease. CONCLUSIONS:
      Intravesical MMC has antitumor activity in dogs with invasive TCC. Further study
      is needed to determine the cause of the myelosuppression associated with MMC
      administration, and to develop strategies to minimize this risk.

PMID- 20695987
TI  - Low-molecular-weight heparin dosage in newborn foals.
AB  - BACKGROUND: Heparin is used in humans as prophylaxis of hypercoagulable states
      and disseminated intravascular coagulation (DIC). However, babies need a higher
      heparin dose than do adults. Septic neonate foals are at high risk of
      hypercoagulable state and DIC, and there is limited objective information about
      heparin dose for equine neonates. OBJECTIVE: To assess whether neonate foals
      require higher dosages of low-molecular-weight heparin (LMWH) than adults.
      ANIMALS: Eighteen healthy and 11 septic neonate foals. METHODS: Experimental and
      clinical studies. Firstly, healthy foals were randomly distributed in 2 groups, 1
      receiving 50 IU/kg SC of dalteparin and the 2nd group receiving 100 IU/kg SC of
      dalteparin, once daily for 3 days. Blood samples were collected before and 3, 6,
      27, and 51 hours after the 1st LMWH administration. Plasma antifactor-Xa activity
      was measured, together with hemostatic and hematologic parameters used to assess
      the risk of bleeding. Subsequently, septic foals were treated blindly either with
      placebo (saline) or 100 IU/kg of dalteparin for 3 days. Plasma antifactor-Xa
      activity and other hemostatic parameters were determined before and after
      treatment. RESULTS: Plasma antifactor-Xa activity in healthy foals was below
      prophylactic activity when using the adult dosage (50 IU/kg), whereas
      prophylactic activities were achieved when using the double dosage (100 IU/kg).
      No hemorrhagic events and erythrocyte-related complications were observed with
      either dosage. In the clinical study, only 4/6 septic foals had plasma antifactor
      Xa activity adequate for prophylaxis. CONCLUSIONS AND CLINICAL IMPORTANCE: Equine
      neonates require higher dosages of LMWH compared with adults to reach
      prophylactic heparinemia.

PMID- 20695988
TI  - Prevalence of urinary tract infection in dogs after surgery for thoracolumbar
      intervertebral disc extrusion.
AB  - BACKGROUND: Urinary tract infection (UTI) is a common complication in people with
      spinal cord injury (SCI). Dogs with acute intervertebral disc extrusion (IVDE)
      have similar risk factors for UTI when compared with human SCI patients and have
      a high perioperative prevalence of UTI. OBJECTIVES: Determine the prevalence of
      UTI in dogs for 3 months after surgery for thoracolumbar IVDE and identify risk
      factors for development of UTI. ANIMALS: Twenty-five dogs treated surgically for
      26 acute disc extrusions. METHODS: Prospective study. Urinalysis and urine
      culture were performed perioperatively. At home, owners monitored urine with
      dipsticks every 48 hours for 1 month then once a week until 3 months. Dogs
      returned for assessment of motor function, urinalysis, and urine culture at 1 and
      3 months after surgery. Presence of UTI over the 3-month period was correlated to
      potential risk factors. RESULTS: Ten dogs (38%) developed 12 UTIs over the 3
      month period, with the majority occurring between weeks 1 and 6; 60% of the UTIs
      were occult. Hematuria in the absence of pyuria or UTI was a common finding in
      the perioperative period. Sex, breed, and ambulatory status influenced the risk
      of developing a UTI. CONCLUSIONS AND CLINICAL IMPORTANCE: There is a high
      prevalence of UTIs, many of which are occult, in the 3 months after surgery for
      thoracolumbar IVDE. These dogs should be routinely monitored for UTI with urine
      culture regardless of urinalysis results.

PMID- 20695989
TI  - Association of iatrogenic hypothyroidism with azotemia and reduced survival time
      in cats treated for hyperthyroidism.
AB  - BACKGROUND: Iatrogenic hypothyroidism can occur after treatment of
      hyperthyroidism, and is correlated with a reduced glomerular filtration rate in
      humans and dogs. HYPOTHESIS: Cats with iatrogenic hypothyroidism after treatment
      for hyperthyroidism will have a greater incidence of azotemia than euthyroid
      cats. ANIMALS: Eighty client owned cats with hyperthyroidism. METHODS: Two
      retrospective studies. (1) Longitudinal study of 12 hyperthyroid cats treated
      with radioiodine (documented as euthyroid after treatment), to assess changes in
      plasma thyroid stimulating hormone (TSH) concentration over a 6-month follow-up
      period, (2) Cross-sectional study of 75 hyperthyroid cats (documented as
      euthyroid) 6 months after commencement of treatment for hyperthyroidism to
      identify the relationship between thyroid status and the development of azotemia.
      Kaplan-Meier survival analysis was performed to identify relationships between
      thyroid and renal status and survival. RESULTS: Plasma TSH concentrations were
      not suppressed in 7 of 8 cats with hypothyroidism 3 months after radioiodine
      treatment. The proportion of cats with azotemia was significantly (P= .028)
      greater in the hypothyroid (16 of 28) than the euthyroid group (14 of 47). Twenty
      eight of 41 cats (68%) with plasma TT4 concentration below the laboratory
      reference range had an increased plasma TSH concentration. Hypothyroid cats that
      developed azotemia within the follow-up period had significantly (P= .018)
      shorter survival times (median survival time 456 days, range 231-1589 days) than
      those that remained nonazotemic (median survival time 905 days, range 316-1869
      days). CONCLUSIONS AND CLINICAL IMPORTANCE: Iatrogenic hypothyroidism appears to
      contribute to the development of azotemia after treatment of hyperthyroidism, and
      reduced survival time in azotemic cats.

PMID- 20695990
TI  - Intravascular occlusion for the correction of extrahepatic portosystemic shunts
      in dogs.
AB  - BACKGROUND: Congential extrahepatic portosystemic shunts (EHPSS) are common in
      dogs. An effective minimally invasive technique for correction of EHPSS could
      result in reduced morbidity, reduced costs, and reduced hospitalization times.
      HYPOTHESIS: Use of an intravascular occlusion device can effectively and safely
      result in acute complete occlusion of EHPSS in dogs. ANIMALS: Seven dogs with
      naturally occurring EHPSS that presented to the Purdue University Veterinary
      Teaching Hospital. METHODS: Prospective, clinical trial. The 7 dogs were
      consecutively enrolled over a 2-year period. Results of serum biochemistry, total
      serum bile acids, fasting plasma ammonia, abdominal radiography, and
      ultrasonography suggested the diagnosis of portosystemic shunts in all dogs.
      Definitive diagnosis of EHPSS was achieved with cranial mesenteric arterial
      portography and acute occlusion was attempted by the deployment of the Amplatzer
      vascular plug (AVP). RESULTS: EHPSS were identified in all dogs consisting of 5
      portocaval and 2 portoazygous variants; 1/7 dogs (14%) were intolerant to
      temporary complete occlusion of the EHPSS. Of the remaining 6 dogs, 5 (83%) had
      complete occlusion of the EHPSS by the AVP. There were no complications and
      resolution of abnormal clinical signs and laboratory values was achieved in 4/5
      (80%) dogs with complete occlusion. CONCLUSIONS AND CLINICAL IMPORTANCE:
      Intravascular correction of EHPSS by the AVP is a viable option to surgical
      correction while larger studies will be required to determine the clinical
      applicability of this procedure in the broader portosystemic shunt population.

PMID- 20695991
TI  - GM2 gangliosidosis variant 0 (Sandhoff-like disease) in a family of toy poodles.
AB  - BACKGROUND: GM2 gangliosidosis variant 0 (human Sandhoff disease) is a lysosomal
      storage disorder caused by deficiencies of acid beta-hexosaminidase (Hex) A and
      Hex B because of an abnormality of the beta-subunit, a common component in these
      enzyme molecules, which is coded by the HEXB gene. OBJECTIVE: To describe the
      clinical, pathological, biochemical, and magnetic resonance imaging (MRI)
      findings of Sandhoff-like disease identified in a family of Toy Poodles. ANIMALS:
      Three red-haired Toy Poodles demonstrated clinical signs including motor
      disorders and tremor starting between 9 and 12 months of age. The animals finally
      died of neurological deterioration between 18 and 23 months of age. There were
      some lymphocytes with abnormal cytoplasmic vacuoles detected. METHODS:
      Observational case study. RESULTS: The common MRI finding was diffuse T2
      hyperintensity of the subcortical white matter in the cerebrum. Bilateral T2
      hyperintensity and T1-hypointensity in the nucleus caudatus, and atrophic
      findings of the cerebrum and cerebellum, were observed in a dog in the late
      stage. Histopathologically, swollen neurons with pale to eosinophilic granular
      materials in the cytoplasm were observed throughout the central nervous system.
      Biochemically, GM2 ganglioside had accumulated in the brain, and Hex A and Hex B
      were deficient in the brain and liver. Pedigree analysis demonstrated that the 3
      affected dogs were from the same family line. CONCLUSIONS AND CLINICAL
      IMPORTANCE: The Sandhoff-like disease observed in this family of Toy Poodles is
      the 2nd occurrence of the canine form of this disease and the 1st report of its
      identification in a family of dogs.

PMID- 20695992
TI  - Suspected needle stick transmission of Bartonella vinsonii subspecies berkhoffii
      to a veterinarian.

PMID- 20695993
TI  - Characterization of Shiga toxin-producing Escherichia coli isolated from dairy
      cows in Argentina.
AB  - AIMS: To feno-genotypically characterize the Shiga toxin-producing Escherichia
      coli (STEC) population in Argentinean dairy cows. METHODS AND RESULTS: From 540
      STEC positive samples, 170 isolates were analyzed by multiplex PCR and
      serotyping. Of these, 11% carried stx1, 52% stx2 and 37% stx1/stx2. The ehxA, saa
      and eae were detected in 77%, 66% and 3%, respectively. Thirty-five per cent of
      strains harboured the profile stx1, stx2, saa, ehxA and 29% stx2, saa, ehxA. One
      hundred and fifty-six strains were associated with 29 different O serogroups, and
      19 H antigens were distributed among 157 strains. STEC O113:H21, O130:H11 and
      O178:H19 were the most frequently found serotypes. The STEC O157:H7 were detected
      in low rate and corresponded to the stx2(+) , eae(+) , ehxA(+) virulence pattern.
      CONCLUSIONS: We detected a diversity of STEC strains in dairy cattle from
      Argentina, most of them carrying genes linked to human disease. SIGNIFICANCE AND
      IMPACT OF THE STUDY: The non-O157 STEC serotypes described in this study are
      associated worldwide with disease in humans and represent a risk for the public
      health. For this, any microbiological control in dairy farms should be targeted
      not only to the search of O157:H7 serotype.

PMID- 20695994
TI  - Substrate specificity of a recombinant D-lyxose isomerase from Serratia
      proteamaculans that produces D-lyxose and D-mannose.
AB  - AIMS: Characterization of substrate specificity of a D-lyxose isomerase from
      Serratia proteamaculans and application of the enzyme in the production of D
      lyxose and D-mannose. METHODS AND RESULTS: The concentrations of monosaccharides
      were determined using a Bio-LC system. The activity of the recombinant protein
      from Ser. proteamaculans was the highest for D-lyxose among aldoses, indicating
      that it is a D-lyxose isomerase. The native recombinant enzyme existed as a 54
      kDa dimer, and the maximal activity for D-lyxose isomerization was observed at pH
      7.5 and 40 degrees C in the presence of 1 mmol l(-1) Mn(2+). The K(m) values for
      D-lyxose, D-mannose, D-xylulose, and D-fructose were 13.3, 32.2, 3.83, and 19.4
      mmol l(-1), respectively. In 2 ml of reaction volume at pH 7.5 and 35 degrees C,
      D-lyxose was produced at 35% (w/v) from 50% (w/v) D-xylulose by the D-lyxose
      isomerase in 3 h, while D-mannose were produced at 10% (w/v) from 50% (w/v) D
      fructose in 5 h. CONCLUSIONS: We identified the putative sugar isomerase from
      Ser. proteamaculans as a D-lyxose isomerase. The enzyme exhibited isomerization
      activity for aldose substrates with the C2 and C3 hydroxyl groups in the left
      hand configuration. High production rates of d-lyxose and d-mannose by the enzyme
      were obtained. SIGNIFICANCE AND IMPACT OF THE STUDY: A new D-lyxose isomerase was
      found, and this enzyme had higher activity for D-lyxose and D-mannose than
      previously reported enzymes. Thus, the enzyme can be applied in industrial
      production of D-lyxose and D-mannose.

PMID- 20695995
TI  - Sensitive and rapid detection of Vibrio corallilyticus by loop-mediated
      isothermal amplification targeted to the alpha subunit gene of RNA polymerase.
AB  - AIMS: A diagnostic protocol was developed for rapid detection of Vibrio
      corallilyticus by method of loop-mediated isothermal amplification (LAMP).
      METHODS AND RESULTS: For cloning and sequencing of rpo A gene of V.
      corallilyticus, a set of four LAMP primers were designed by targeting the rpoA
      gene. With Bst DNA polymerase, the reaction time and temperature were optimized
      for 70 min at 65 degrees C, respectively. The amplification products were
      detected by electrophoresis. The detection limit of V. corallilyticus by LAMP was
      3.6 x 10(3) CFU ml(-1) (8 CFU per reaction), but PCR could detect up to 3.6 x
      10(4) CFU ml(-1) (72 CFU per reaction). The LAMP method was ninefold more
      sensitive than conventional PCR. The results also indicated that the LAMP
      reaction was highly specific to V. corallilyticus. CONCLUSIONS: The LAMP assay
      was a sensitive, specific and cost-effective method for the rapid detection of V.
      corallilyticus. SIGNIFICANCE AND IMPACT OF THE STUDY: This LAMP method provides
      an important diagnostic tool for the detection of V. corallilyticus infection. It
      can replace laborious biochemical tests for the identification of V.
      corallilyticus.

PMID- 20695996
TI  - Parallel habitat specialization within the wolf spider genus Hogna from the
      Galapagos.
AB  - Within most island archipelagos, such as the Galapagos, similar ecological
      gradients are found on geographically isolated islands. Species radiations in
      response to these ecological gradients may follow different scenarios being (i) a
      single habitat specialization event followed by secondary colonization of each
      ecotype on the different islands or (ii) repeated and parallel habitat
      specialization on each island separately. This latter scenario has been
      considered less likely as gene flow might hamper such ecotypic differentiation.
      At least for the Galapagos, the extent to which this process is involved in
      species radiations remains yet poorly understood. Within the wolf spider genus
      Hogna, seven species are described that can be divided into three different
      ecotypes based on general morphology and habitat preference i.e. species that
      inhabit the pampa vegetation in the highlands, species that occur in coastal dry
      habitats and one generalist species. Comparison of the species phylogeny based on
      one mitochondrial (COI) and one nuclear (28S) gene fragment convincingly
      demonstrates that 'pampa' and 'coastal dry' species evolved in parallel on the
      islands Santa Cruz and San Cristobal. Despite the observation that allozymes
      analysis indicated that each species forms a distinct genetic cluster,
      phylogenetic divergence within these species complexes was very low and
      paraphyletic and most likely due to hybridization rather than incomplete lineage
      sorting, as demonstrated for the Santa Cruz species complex. This suggests that
      within-island speciation occurred under low levels of gene flow. Species
      phylogeny in general did not follow the progression of island emergence as a
      molecular clock analysis suggested that island endemic species may have diverged
      after as well as before the emergence of the islands. This represents the first
      clear example of parallel and within-island speciation because of habitat
      specialization on the Galapagos and that such divergence most likely occurred
      under historic gene flow.

PMID- 20695998
TI  - Lecanicillium fungicola: causal agent of dry bubble disease in white-button
      mushroom.
AB  - Lecanicillium fungicola causes dry bubble disease in commercially cultivated
      mushroom. This review summarizes current knowledge on the biology of the pathogen
      and the interaction between the pathogen and its most important host, the white
      button mushroom, Agaricus bisporus. The ecology of the pathogen is discussed with
      emphasis on host range, dispersal and primary source of infection. In addition,
      current knowledge on mushroom defence mechanisms is reviewed. TAXONOMY:
      Lecanicillium fungicola (Preuss) Zare and Gams: Kingdom Fungi; Phylum Ascomycota;
      Subphylum Pezizomycotina; Class Sordariomycetes; Subclass Hypocreales; Order
      Hypocreomycetidae; Family Cordycipitaceae; genus Lecanicillium. HOST RANGE:
      Agaricus bisporus, Agaricus bitorquis and Pleurotus ostreatus. Although its
      pathogenicity for other species has not been established, it has been isolated
      from numerous other basidiomycetes. DISEASE SYMPTOMS: Disease symptoms vary from
      small necrotic lesions on the caps of the fruiting bodies to partially deformed
      fruiting bodies, called stipe blow-out, or totally deformed and undifferentiated
      masses of mushroom tissue, called dry bubble. The disease symptoms and severity
      depend on the time point of infection. Small necrotic lesions result from late
      infections on the fruiting bodies, whereas stipe blow-out and dry bubble are the
      result of interactions between the pathogen and the host in the casing layer.
      ECONOMIC IMPORTANCE: Lecanicillium fungicola is a devastating pathogen in the
      mushroom industry and causes significant losses in the commercial production of
      its main host, Agaricus bisporus. Annual costs for mushroom growers are estimated
      at 2-4% of total revenue. Reports on the disease originate mainly from North
      America and Europe. Although China is the main producer of white-button mushrooms
      in the world, little is known in the international literature about the impact of
      dry bubble disease in this region. CONTROL: The control of L. fungicola relies on
      strict hygiene and the use of fungicides. Few chemicals can be used for the
      control of dry bubble because the host is also sensitive to fungicides. Notably,
      the development of resistance of L. fungicola has been reported against the
      fungicides that are used to control dry bubble disease. In addition, some of
      these fungicides may be banned in the near future. USEFUL WEBSITES:
      http://www.mycobank.org; http://www.isms.biz; http://www.cbs.knaw.nl.

PMID- 20695999
TI  - SGT1 positively regulates the process of plant cell death during both compatible
      and incompatible plant-pathogen interactions.
AB  - SGT1 (suppressor of G2 allele of Skp1), an interactor of SCF (Skp1-Cullin-F-box)
      ubiquitin ligase complexes that mediate protein degradation, plays an important
      role at both G1-S and G2-M cell cycle transitions in yeast, and is highly
      conserved throughout eukaryotes. Plant SGT1 is required for both resistance (R)
      gene-mediated disease resistance and nonhost resistance to certain pathogens.
      Using virus-induced gene silencing (VIGS) in Nicotiana benthamiana, we
      demonstrate that SGT1 positively regulates the process of cell death during both
      host and nonhost interactions with various pathovars of Pseudomonas syringae.
      Silencing of NbSGT1 in N. benthamiana plants delays the induction of
      hypersensitive response (HR)-mediated cell death against nonhost pathogens and
      the development of disease-associated cell death caused by the host pathogen P.
      syringae pv. tabaci. Our results further demonstrate that NbSGT1 is required for
      Erwinia carotovora- and Sclerotinia sclerotiorum-induced disease-associated cell
      death. Overexpression of NbSGT1 in N. benthamiana accelerates the development of
      HR during R gene-mediated disease resistance and nonhost resistance. Our data
      also indicate that SGT1 is required for pathogen-induced cell death, but is not
      always necessary for the restriction of bacterial multiplication in planta.
      Therefore, we conclude that SGT1 is an essential component affecting the process
      of cell death during both compatible and incompatible plant-pathogen
      interactions.

PMID- 20696000
TI  - Inadvertent gene silencing of argininosuccinate synthase (bcass1) in Botrytis
      cinerea by the pLOB1 vector system.
AB  - For several years, researchers working on the plant pathogen Botrytis cinerea and
      a number of other related fungi have routinely used the pLOB1 vector system,
      based on hygromycin resistance, under the control of the Aspergillus nidulans
      oliC promoter and what was reported to be the beta-tubulin (tubA) terminator.
      Recently, it has been demonstrated that this vector contains a 446-bp portion of
      the B. cinerea argininosuccinate synthase gene (bcass1) rather than the tubA
      terminator. As argininosuccinate synthase is essential for the production of L
      arginine, inadvertent gene silencing of bcass1 may result in partial L-arginine
      auxotrophy and, indeed, may lead to altered phenotypes in planta. In this
      article, we report our findings relating to possible problems arising from this
      incorrect plasmid construction. As an absolute baseline, gene disruption of
      bcass1 was carried out and generated a strict auxotroph, unable to grow without
      exogenous arginine supplementation. The knockout displayed an alteration in host
      range in planta, showing a reduction in pathogenicity on strawberries, French
      bean leaves and tomatoes, but maintained wild-type growth on grape, which is in
      accordance with the reported arginine availability in such tissues. Deliberate
      gene silencing of bcass1 mirrored these effects, with strongly silenced lines
      showing reduced virulence. The degree of silencing as seen by partial auxotrophy
      was correlated with an observed reduction in virulence. We also showed that
      inadvertent silencing of bcass1 is possible when using the pLOB1 vector or
      derivatives thereof. Partial arginine auxotrophy and concomitant reductions in
      virulence were triggered in approximately 6% of transformants obtained when
      expressing enhanced green fluorescent protein, luciferase, monomeric red
      fluorescent protein or beta-glucuronidase using the pLOB1-based expression
      system, which inadvertently contains 446 bp of the bcass1 coding sequence. We
      recommend the testing of transformants obtained using this vector system for
      arginine auxotrophy in order to provide assurance that any observed effects on
      the development or virulence are a result of the desired genetic alteration
      rather than accidental bcass1 silencing.

PMID- 20696001
TI  - Cellular and transcriptional responses of wheat during compatible and
      incompatible race-specific interactions with Puccinia striiformis f. sp. tritici.
AB  - The initial stages of Puccinia striiformis f. sp. tritici (the causal agent of
      yellow rust in wheat) infection triggered a hypersensitive cell death (HCD)
      response in both compatible and Yr1-mediated incompatible interactions, although
      the response was earlier and more extensive in the incompatible interaction.
      Later stages of fungal development were only associated with an HCD response in
      the incompatible interaction, the HCD response being effectively suppressed in
      the compatible interaction. Cell autofluorescence was seen in mesophyll cells in
      direct contact with fungal infection hyphae (primary HCD) and in adjacent
      mesophyll cells (secondary HCD), indicating the activation of cell-to-cell
      signalling. Microarray analysis identified a number of defence-related
      transcripts implicated in Yr1-mediated resistance, including classical
      pathogenesis-related (PR) transcripts and genes involved in plant cell defence
      responses, such as the oxidative burst and cell wall fortification. A
      quantitative reverse transcriptase-polymerase chain reaction time course analysis
      identified a number of defence-related genes, including PR2, PR4, PR9, PR10 and
      WIR1 transcripts, associated with the latter stages of Yr1-mediated resistance. A
      meta-analysis comparison of the Yr1-regulated transcriptome with the resistance
      transcriptomes of the race-specific resistance gene Yr5 and the race-nonspecific
      adult plant resistance gene Yr39 indicated limited transcript commonality. Common
      transcripts were largely confined to classic PR and defence-related genes.

PMID- 20696002
TI  - The silencing suppressor P25 of Potato virus X interacts with Argonaute1 and
      mediates its degradation through the proteasome pathway.
AB  - Previous evidence has indicated that the P25 protein encoded by Potato virus X
      (PVX) inhibits either the assembly or function of the effector complexes in the
      RNA silencing-based antiviral defence system (Bayne et al., Cell-to-cell movement
      of Potato Potexvirus X is dependent on suppression of RNA silencing. Plant J.44,
      471-482). This finding prompted us to investigate the possibility that P25
      targets the Argonaute (AGO) effector nuclease of RNA silencing. Co
      immunoprecipitation and Western blot analysis indicated that there is a strong
      interaction between P25 and AGO1 of Arabidopsis when these proteins are
      transiently co-expressed in Nicotiana benthamiana. P25 also interacts with AGO1,
      AGO2, AGO3 and AGO4, but not with AGO5 and AGO9. As an effective suppressor, the
      amount of AGO1 accumulated in the presence of P25 was dramatically lower than
      that infiltrated with HcPro, but was restored when treated with a proteasome
      inhibitor MG132. These findings are consistent with the idea that RNA silencing
      is an antiviral defence mechanism and that the counter-defence role of P25 is
      through the degradation of AGO proteins via the proteasome pathway. Further
      support for this idea is provided by the observation that plants treated with
      MG132 are less susceptible to PVX and its relative Bamboo mosaic virus.

PMID- 20696003
TI  - A single-stranded conformational polymorphism (SSCP)-derived quantitative
      variable to monitor the virulence of a Barley yellow dwarf virus-PAV (BYDV-PAV)
      isolate during adaptation to the TC14 resistant wheat line.
AB  - A standardized single-stranded conformational polymorphism (SSCP) procedure is
      proposed as an alternative to the time-consuming biological characterization of
      Barley yellow dwarf virus-PAV (BYDV-PAV) isolates. Using this procedure, six of
      21 overlapping regions used to scan the viral genome gave patterns specific to
      '4E' (avirulent) or '4T' ('4E'-derived virulent) isolates. The calibration of
      samples and integration of SSCP patterns corresponding to the nucleotide region
      1482-2023 allowed the estimation of P(T) values that reflect the proportions of a
      '4T'-specific band. Analysis of the biological (area under the pathogen progress
      curve) and molecular (P(T)) data suggested a positive linear relation between
      these variables. Moreover, sequence analysis of the nucleotide region 1482-2023
      highlighted the presence of a nucleotide polymorphism (C/A(1835)) which can be
      considered as a candidate for virus-host interactions linked to the monitored
      virulence. According to these parameters, P(T) values associated with '4E'- and
      '4T'-derived populations show that: (i) long-term infection of a BYDV-PAV isolate
      on the 'TC14' resistant host leads to the fixation of virulent individuals in
      viral populations; and (ii) the introduction of susceptible hosts in successive
      'TC14' infections results in the maintenance of low virulence of the populations.
      Thus, the presented study demonstrates that SSCP is a useful tool for monitoring
      viral populations during the host adaptation process. The described impact of
      host alternation provides new opportunities for the use of the 'TC14' resistance
      source in BYDV-resistant breeding programmes. This study is part of the global
      effort made by the scientific community to propose sustainable alternatives to
      the chemical control of this viral disease.

PMID- 20696004
TI  - The Xanthomonas citri effector protein PthA interacts with citrus proteins
      involved in nuclear transport, protein folding and ubiquitination associated with
      DNA repair.
AB  - Xanthomonas axonopodis pv. citri utilizes the type III effector protein PthA to
      modulate host transcription to promote citrus canker. PthA proteins belong to the
      AvrBs3/PthA family and carry a domain comprising tandem repeats of 34 amino acids
      that mediates protein-protein and protein-DNA interactions. We show here that
      variants of PthAs from a single bacterial strain localize to the nucleus of plant
      cells and form homo- and heterodimers through the association of their repeat
      regions. We hypothesize that the PthA variants might also interact with distinct
      host targets. Here, in addition to the interaction with alpha-importin, known to
      mediate the nuclear import of AvrBs3, we describe new interactions of PthAs with
      citrus proteins involved in protein folding and K63-linked ubiquitination. PthAs
      2 and 3 preferentially interact with a citrus cyclophilin (Cyp) and with TDX, a
      tetratricopeptide domain-containing thioredoxin. In addition, PthAs 2 and 3, but
      not 1 and 4, interact with the ubiquitin-conjugating enzyme complex formed by
      Ubc13 and ubiquitin-conjugating enzyme variant (Uev), required for K63-linked
      ubiquitination and DNA repair. We show that Cyp, TDX and Uev interact with each
      other, and that Cyp and Uev localize to the nucleus of plant cells. Furthermore,
      the citrus Ubc13 and Uev proteins complement the DNA repair phenotype of the
      yeast Deltaubc13 and Deltamms2/uev1a mutants, strongly indicating that they are
      also involved in K63-linked ubiquitination and DNA repair. Notably, PthA 2
      affects the growth of yeast cells in the presence of a DNA damage agent,
      suggesting that it inhibits K63-linked ubiquitination required for DNA repair.

PMID- 20696005
TI  - Agrobacterium-produced and exogenous cytokinin-modulated Agrobacterium-mediated
      plant transformation.
AB  - Agrobacterium tumefaciens is a plant pathogenic bacterium that causes neoplastic
      growths, called 'crown gall', via the transfer and integration of transferred DNA
      (T-DNA) from the bacterium into the plant genome. We characterized an
      acetosyringone (AS)-induced tumour-inducing (Ti) plasmid gene, tzs (trans-zeatin
      synthesizing), that is responsible for the synthesis of the plant hormone
      cytokinin in nopaline-type A. tumefaciens strains. The loss of Tzs protein
      expression and trans-zeatin secretions by the tzs frameshift (tzs-fs) mutant is
      associated with reduced tumorigenesis efficiency on white radish stems and
      reduced transformation efficiencies on Arabidopsis roots. Complementation of the
      tzs-fs mutant with a wild-type tzs gene restored wild-type levels of trans-zeatin
      secretions and transformation efficiencies. Exogenous application of cytokinin
      during infection increased the transient transformation efficiency of Arabidopsis
      roots infected by strains lacking Tzs, which suggests that the lower
      transformation efficiency resulted from the lack of Agrobacterium-produced
      cytokinin. Interestingly, although the tzs-fs mutant displayed reduced
      tumorigenesis efficiency on several tested plants, the loss of Tzs enhanced
      tumorigenesis efficiencies on green pepper and cowpea. These data strongly
      suggest that Tzs, by synthesizing trans-zeatin at early stage(s) of the infection
      process, modulates plant transformation efficiency by A. tumefaciens.

PMID- 20696006
TI  - New capabilities for Mycosphaerella graminicola research.
AB  - Mycosphaerella graminicola is a major pathogen of wheat worldwide, causing
      Septoria leaf blotch disease. Targeted gene disruption in M. graminicola, by
      Agrobacterium tumefaciens-mediated transformation, has become an established
      functional genomics tool for M. graminicola research in recent years. However, in
      order to advance research into this economically important pathogen, further
      functional genomics tools need to be developed. Here, we report three new
      capabilities for M. graminicola research: (i) two selectable markers have been
      shown to work robustly in M. graminicola, namely G418 and the fungicide carboxin;
      (ii) the generation of a strain of M. graminicola in which the KU70 (MUS-51)
      homologue has been disrupted; in this strain, homologous recombination
      efficiencies increased to more than 95%, whilst maintaining wild-type growth in
      vitro and full pathogenicity on wheat leaves; (iii) the ability to efficiently
      target and generate precise mutations of specific genes in the genomic context in
      M. graminicola. In addition, the insertion of the E198A mutation into the beta
      tubulin gene (MgTUB1), conferring resistance to the fungicide benomyl, suggests
      that this mutant allele may provide an additional selectable marker. The
      collective use of these tools will permit further advancements in our knowledge
      of the biology and pathogenicity of this important plant pathogen.

PMID- 20696007
TI  - The roles of plant phenolics in defence and communication during Agrobacterium
      and Rhizobium infection.
AB  - Phenolics are aromatic benzene ring compounds with one or more hydroxyl groups
      produced by plants mainly for protection against stress. The functions of
      phenolic compounds in plant physiology and interactions with biotic and abiotic
      environments are difficult to overestimate. Phenolics play important roles in
      plant development, particularly in lignin and pigment biosynthesis. They also
      provide structural integrity and scaffolding support to plants. Importantly,
      phenolic phytoalexins, secreted by wounded or otherwise perturbed plants, repel
      or kill many microorganisms, and some pathogens can counteract or nullify these
      defences or even subvert them to their own advantage. In this review, we discuss
      the roles of phenolics in the interactions of plants with Agrobacterium and
      Rhizobium.

PMID- 20696008
TI  - A series of Chinese patients with desminopathy associated with six novel and one
      reported mutations in the desmin gene.
AB  - AIMS: Desminopathy is a hereditary cardiac and skeletal myopathy caused by
      mutations in the desmin gene. This study summarizes the clinical, myopathological
      and genetic features of a series of Chinese patients with desminopathy. METHODS:
      Thirty-nine cases from five families with autosomal dominant inheritance and two
      sporadic cases were investigated. The majority of patients presented with mild
      myopathy and prominent cardiomyopathy. Fifteen of 16 deceased cases died of
      cardiac causes. Of the 25 patients alive, 24 patients developed cardiac
      abnormalities with disease progression. Muscle specimens from nine patients were
      investigated in various morphological examinations. Gene sequencing and cell
      transfections were performed to determine whether the mutant desmin formed
      intermediate filaments. RESULTS: Muscle biopsies revealed 5 cases with dystrophy
      like patterns and amorphous material deposits; four other cases showed myopathy
      like patterns with cytoplasmic bodies or nemaline bodies. Desmin and multiple
      proteins aggregated in the affected fibres. Six novel mutations and one
      previously reported mutation in the desmin gene were identified in the patients.
      All the mutant desmin genes except E457V produced multiple desmin-positive clumps
      or abnormal solid large aggregates in transfected cells. CONCLUSIONS: This study
      enlarges the spectrum of desmin mutations and geographic distribution of
      desminopathy. Although many novel mutations were identified in Chinese patients,
      the main clinical and myopathological findings were similar to those in Caucasian
      patients. Cardiac conduction abnormalities were prominent and usually appeared
      later than skeletal myopathy. The myopathology exhibited some heterogeneity among
      our patients, but the pathological changes were not indicative of the mutation
      location in the desmin gene.

PMID- 20696009
TI  - The SOS1 transporter of Physcomitrella patens mediates sodium efflux in planta.
AB  - * SOS1 is an Na(+)/H(+) antiporter that plays a central role in Na(+) tolerance
      in land plants. SOS1 mediation of Na(+) efflux has been studied in plasma
      membrane vesicles and deduced from the SOS1 suppression of the Na(+) sensitivity
      of yeast mutants defective in Na(+) -efflux. However, SOS1-mediated Na(+) efflux
      has not been characterized in either plant or yeast cells. Here, we use
      Physcomitrella patens to investigate the function of SOS1 in planta. * In P.
      patens, a nonvascular plant in which the study of ion cellular fluxes is
      technically simple, the existence of two SOS1 genes suggests that the Na(+)
      efflux remaining after the deletion of the ENA1 ATPase is mediated by a SOS1
      system. Therefore, we cloned the P. patens SOS1 and SOS1B genes (PpSOS1 and
      PpSOS1B, respectively) and complementary DNAs, and constructed the PpDeltasos1
      and PpDeltaena1/PpDeltasos1 deletion lines by gene targeting. * Comparison of
      wild-type, and PpDeltasos1 and PpDeltaena1/PpDeltasos1 mutant lines revealed that
      PpSOS1 is crucial for Na(+) efflux and that the PpDeltasos1 line, and especially
      the PpDeltaena1/PpDeltasos1 lines, showed excessive Na(+) accumulation and Na(+)
      triggered cell death. The PpDeltasos1 and PpDeltaena1/PpDeltasos1 lines showed
      impaired high-affinity K(+) uptake. * Our data support the hypothesis that PpSOS1
      mediates cellular Na(+) efflux and that PpSOS1 enhances K(+) uptake by an
      indirect effect.

PMID- 20696010
TI  - Phenotypic plasticity despite source-sink population dynamics in a long-lived
      perennial plant.
AB  - * Species that exhibit adaptive plasticity alter their phenotypes in response to
      environmental conditions, thereby maximizing fitness in heterogeneous landscapes.
      However, under demographic source-sink dynamics, selection should favor traits
      that enhance fitness in the source habitat at the expense of fitness in the
      marginal habitat. Consistent with source-sink dynamics, the perennial blueberry,
      Vaccinium elliottii (Ericaceae), shows substantially higher fitness and
      population sizes in dry upland forests than in flood-prone bottomland forests,
      and asymmetrical gene flow occurs from upland populations into bottomland
      populations. Here, we examined whether this species expresses plasticity to these
      distinct environments despite source-sink dynamics. * We assessed phenotypic
      responses to a complex environmental gradient in the field and to water stress in
      the glasshouse. * Contrary to expectations, V. elliottii exhibited a high degree
      of plasticity in foliar and root traits (specific leaf area, carbon isotope
      ratios, foliar nitrogen content, root : shoot ratio, root porosity and root
      architecture). * We propose that plasticity can be maintained in source-sink
      systems if it is favored within the source habitat and/or a phylogenetic artifact
      that is not costly. Additionally, plasticity could be advantageous if habitat
      based differences in fitness result from incipient niche expansion. Our results
      illuminate the importance of evaluating phenotypic traits and fitness components
      across heterogeneous landscapes.

PMID- 20696011
TI  - The population genomics of plant adaptation.
AB  - There has been an enormous increase in the amount of data on DNA sequence
      polymorphism available for many organisms in the last decade. New sequencing
      technologies provide great potential for investigating natural selection in
      plants using population genomic approaches. However, plant populations frequently
      show significant departures from the assumptions of standard models used to
      detect selection and many forms of directional selection do not fit with
      classical population genetics theory. Here, we explore the extent to which plant
      populations show departures from standard model assumptions, and the implications
      this has for detecting selection on molecular variation. A growing number of
      multilocus studies of nucleotide variation suggest that changes in population
      size, particularly bottlenecks, and strong subdivision may be common in plants.
      This demographic variation presents important challenges for models used to infer
      selection. In addition, selection from standing genetic variation and multiple
      independent adaptive substitutions can further complicate efforts to understand
      the nature of selection. We discuss emerging patterns from plant studies and
      propose that, rather than treating population history as a nuisance variable when
      testing for selection, the interaction between demography and selection is of
      fundamental importance for evolutionary studies of plant populations using
      molecular data.

PMID- 20696012
TI  - Immunological contribution to the pathogenesis of congenital heart block.

PMID- 20696014
TI  - Autoantibodies associated with congenital heart block.
AB  - Congenital heart block is the most severe manifestation of neonatal lupus
      syndrome. It is a passively acquired disease where transplacental passage of
      maternal autoantibodies is associated with irreversible damage of the foetal
      cardiac conduction system. It is well established that the condition, in the
      absence of structural abnormalities, is strongly associated with maternal
      autoantibodies to the Ro/La antigens. More specifically the disease has been
      closely linked to antibodies to the Ro52 component of the antigen complex.
      Congenital heart block constitutes a unique model where specific autoantibodies
      target and mediate organ-specific disease. A wide panel of maternal antibodies
      has been discussed in literature in association with the disease and are
      described in this review.

PMID- 20696015
TI  - Spectrum of cardiac involvement in neonatal lupus.
AB  - 'Neonatal' lupus erythematosus (NLE) describes a clinical spectrum of cardiac and
      non-cardiac abnormalities observed in neonates and foetuses whose mothers have
      the auto-antibodies anti-SSA/Ro (anti-Ro) and anti-SSB/La (anti-La). Of the
      cardiac abnormalities, congenital AVB is the most common cardiovascular
      abnormality found in affected foetuses and infants. Many other cardiovascular
      manifestations of NLE have been more recently recognized including atrial and
      ventricular arrhythmias and other conduction abnormalities, myocarditis,
      cardiomyopathy often with endocardiofibroelastosis and structural heart disease,
      particularly valvar lesions. In this report, the spectrum of cardiovascular
      manifestations observed in foetuses and infants with NLE are reviewed and the
      pathogenesis, diagnosis and clinical outcomes are briefly discussed.

PMID- 20696013
TI  - Effector and regulatory T-cell subsets in autoimmunity and tissue inflammation.
AB  - Many autoimmune diseases are driven by self-reactive T helper cells. Until
      recently, organ-specific autoimmune diseases were primarily associated with Th1
      cells but not Th2 cells. However, the discovery of a number of new effector T
      cell subsets, like Th17 and Th9 cells, and regulatory T cells, like Tregs and Tr1
      cells, has changed the way we view and understand autoimmunity at cellular and
      molecular levels. In recent years, IL-17-producing Th17 cells have emerged as
      major players in autoimmunity. The complicated relationship between Th1 and Th17
      cells, as well as the intricate balance between Tregs and Th17 cells, provides a
      basis for understanding the immunological mechanisms that induce and regulate
      autoimmunity. Here, we give an overview of the interplay between different
      effector T-cell subsets and regulatory T-cell subsets, and how they contribute to
      the development of autoimmunity and tissue inflammation.

PMID- 20696016
TI  - Arrhythmias presenting in neonatal lupus.
AB  - Perfusion of human foetal heart with anti-Ro/SSA antibodies induces transient
      heart block. Anti-Ro/SSA antibodies may cross-react with T- and L-type calcium
      channels, and anti-p200 antibodies may cause calcium to accumulate in rat heart
      cells. These actions may explain a direct electrophysiological effect of these
      antibodies. Congenital complete heart block is the more severe manifestation of
      so-called "Neonatal Lupus". In clinical practice, it is important to distinguish
      in utero complete versus incomplete atrioventricular (AV) block, as complete AV
      block to date is irreversible, while incomplete AV block has been shown to be
      potentially reversible after fluorinated steroid therapy. Another issue is the
      definition of congenital AV block, as cardiologists have considered congenital
      blocks detected months or years after birth. We propose as congenital blocks
      detected in utero or within the neonatal period (0-27 days after birth). The
      possible detection of first degree AV block in utero, with different techniques,
      might be a promising tool to assess the effects of these antibodies. Other
      arrhythmias have been described in NL or have been linked to anti-Ro/SSA
      antibodies: first degree AV block, in utero and after birth, second degree (i.e.
      incomplete block), sinus bradycardia and QT prolongation, both in infants and in
      adults, ventricular arrhythmias (in adults). Overall, these arrhythmias have not
      a clinical relevance, but are important for research purposes.

PMID- 20696017
TI  - Diagnosing foetal atrioventricular heart blocks.
AB  - Foetal echocardiographic ultrasound techniques still remain the dominating
      modality for diagnosing foetal atrioventricular block (AVB). Foetal
      electrocardiography might become a valuable tool to measure time intervals, but
      magnetocardiography is unlikely to get a place in clinical practice. Assuming
      that AVB is a gradually progressing and preventable disease, starting during a
      critical period in mid-gestation with a less abnormal atrioventricular conduction
      before progressing to a complete irreversible AVB (CAVB), echocardiographic
      methods to detect first-degree AVB have been developed. The time intervals
      obtained with these techniques are all based on the identification of mechanical
      or hemodynamic events as markers of atrial (A) and ventricular (V)
      depolarizations and will accordingly include both electrical and mechanical
      components. Prospective observational studies have demonstrated a transient
      prolongation of AV time intervals in anti-Ro/SSA antibody-exposed foetuses, but
      it has not succeeded to identify a degree of AV time prolongation predicting
      irreversible cardiac damage and progression to CAVB. Causes of sustained
      bradycardia include CAVB, 2:1 AVB, sinus bradycardia and blocked atrial bigeminy
      (BAB). Using foetal echocardiographic techniques and a systematic approach, a
      correct diagnosis can be made in almost every case. Sinus bradycardia and CAVB
      are usually easy to diagnose, but BAB has a tendency to be sustained and shows a
      high degree of resemblance with 2:1 AVB when diagnosed during mid-gestational. As
      BAB resolves without treatment and 2:1 AVB may respond to treatment with
      fluorinated steroids, a correct diagnosis becomes an issue of major importance to
      avoid unnecessary treatment of harmless and spontaneously reversing conditions.

PMID- 20696018
TI  - Anti-Ro/SSA antibodies and cardiac arrhythmias in the adult: facts and
      hypotheses.
AB  - It is well established that the passive trans-placental passage of anti-Ro/SSA
      antibodies from mother to foetus is associated with the risk to develop an
      uncommon syndrome named neonatal lupus (NLE), where the congenital heart block
      represents the most severe clinical feature. Recent evidence demonstrated that
      also adult heart, classically considered invulnerable to the anti-Ro/SSA
      antibodies, may represent a target of the arrhythmogenicity of these
      autoantibodies. In particular, the prolongation of the QTc interval appears the
      most frequent abnormality observed in adults with circulating anti-Ro/SSA
      antibodies, with some data suggesting an association with an increased risk of
      ventricular arrhythmias, also life threatening. Moreover, even though the
      association between anti-Ro/SSA antibodies and conduction disturbances is
      undoubtedly less evident in adults than in infants, from the accurate dissection
      of the literature data the possibility arises that sometimes also the adult
      cardiac conduction tissue may be affected by such antibodies. The exact
      arrhythmogenic mechanisms involved in foetus/newborns and adults, respectively,
      have not been completely clarified as yet. However, increasing evidence suggests
      that anti-Ro/SSA antibodies may trigger rhythm disturbances through an inhibiting
      cross-reaction with several cardiac ionic channels, particularly the calcium
      channels (L-type and T-type), but also the potassium channel hERG, whose
      different expression and involvement in the cardiac electrophysiology during
      lifespan might account for the occurrence of age-related differences.

PMID- 20696019
TI  - Non-cardiac manifestations of neonatal lupus erythematosus.
AB  - Neonatal lupus erythematosus (NLE) is characterized by the transplacental passage
      of maternal anti-Ro and/or anti-La antibodies and characteristic illnesses in the
      foetus/neonate. Most attention has focused on the most serious complication-
      cardiac involvement. This article will focus on non-cardiac involvement. Skin
      involvement (cutaneous NLE) is present in 15-25% of children with NLE. The rash
      of NLE tends to be photosensitive but may be present at birth or in non-sun
      exposed areas. It is most frequently seen around the eyes, not in the malar area,
      but also occurs in other parts of the body. The pathology resembles the rash of
      subacute cutaneous lupus erythematosus. Anti-Ro antibodies are present in >95%
      with the remaining mothers having anti-U1RNP antibodies only. Asymptomatic
      elevation of liver function tests, which may be associated with evidence of
      cholestasis, is seen in 10-25% of cases of NLE. Mild hepatomegaly and less
      commonly splenomegaly may be present. Liver involvement seen in isolation or
      associated with other features. The pathology resembles idiopathic neonatal giant
      cell hepatitis. Any haematological lineage, neutropenia and thrombocytopenia most
      commonly, may be affected by NLE. Haematological involvement is almost always
      asymptomatic. There are protean manifestations of neurologic involvement in NLE:
      hydrocephalus, non-specific white matter changes, calcification of the basal
      ganglia and a 'vasculopathy'. The most unusual feature of NLE is the radiographic
      finding of stippling of the epiphyses (chondrodysplasia punctata). Overall, non
      cardiac involvement of NLE is more common than cardiac. The study of these
      manifestations may lead to new insight into how autoantibodies lead to disease.

PMID- 20696021
TI  - The benefits of transplacental treatment of isolated congenital complete heart
      block associated with maternal anti-Ro/SSA antibodies: a review.
AB  - Isolated congenital complete atrio-ventricular block (CAVB) is associated with
      the transplacental passage of maternal autoantibodies directed to foetal Ro/SSA
      ribonucleoproteins. Their interactions most likely trigger the inflammation of
      the atrio-ventricular node and the myocardium in susceptible foetuses. The
      inflamed tissues may then heal with fibrosis that may cause heart block,
      endocardial fibroelastosis, and dilated cardiomyopathy. CAVB, the most common
      cardiac complication, typically develops between 18 and 24 gestational weeks.
      Untreated, the condition carries a significant mortality risk as the foetus needs
      to overcome the sudden drop in ventricular rate, the loss of normal atrial
      systolic contribution to ventricular filling, and perhaps concomitant myocardial
      inflammation and fibrosis. The rationale to treat a foetus at the stage of CAVB
      is primarily to mitigate myocardial inflammation and to augment foetal cardiac
      output. Maternal dexamethasone administration has been shown to improve
      incomplete foetal AV block, myocardial dysfunction, and cavity effusions. Beta
      sympathomimetics may be useful to increase the foetal heart rate and myocardial
      contractility. Published data from our institution suggest an improved survival
      >90% if maternal high-dose dexamethasone was initiated at the time of CAVB
      detection and maintained during the pregnancy and if a beta-adrenergic drug was
      added at foetal heart rates below 55 beats/min. Despite the improvement in
      outcome, there is an ongoing debate about treatment-related risks. In this
      review, we will appraise the natural history of untreated CAVB, discuss currently
      available management options, and examine the results and risks of in-utero
      treatment of antibody-mediated CAVB.

PMID- 20696020
TI  - Role of calcium channels in congenital heart block.
AB  - Congenital heart block (CHB) is a conduction abnormality that affects hearts of
      foetuses and/or newborn to mothers with autoantibodies reactive with the
      intracellular soluble ribonucleoproteins 48-kD La, 52-kD Ro and 60-kD Ro. CHB
      carries substantial mortality and morbidity, with more than 60% of affected
      children requiring lifelong pacemakers. Several hypotheses have been proposed to
      explain the pathogenesis of CHB. These can be grouped under three main
      hypotheses: Apoptosis, Serotoninergic and Ca channel hypothesis. Here, we discuss
      these hypotheses and provide recent scientific thinking that will most likely
      dominate the future of this field of research.

PMID- 20696022
TI  - Intravenous administration of bone marrow mesenchymal stem cells benefits
      experimental autoimmune myasthenia gravis mice through an immunomodulatory
      action.
AB  - Mesenchymal stem cells (MSC) are potent in immunomodulation. It has been proven
      that MSC functioned to correct immune disorder in several immune diseases. Here,
      we tested the hypothesis that MSC from human bone marrow (hMSC) can provide a
      potential therapy for experimental autoimmune myasthenia gravis (EAMG). EAMG mice
      model was established by subcutaneous injection of synthetic analogue of
      acetylcholine receptor (AchR), then, hMSC were intravenously delivered into these
      mice repeatedly. The results showed that hMSC could specifically home to spleen
      tissue and hMSC treatment significantly improved the functional deficits of EAMG
      mice. In addition, AchR antibody level was dramatically decreased in cell-treated
      group when compared with untreated control on 10 days after the second cell
      injection. Moreover, both in vivo and in vitro mixed lymphocyte proliferation
      assays revealed that hMSC could definitely inhibit the proliferation of AchR
      specific lymphocyte. In conclusion, our study demonstrated that hMSC treatment
      was therapeutically useful in autoimmune myasthenia gravis mice, and the
      underlying mechanism may relate with their immunomodulatory potential.

PMID- 20696023
TI  - Differentiation imbalance of Th1/Th17 in peripheral blood mononuclear cells might
      contribute to pathogenesis of Hashimoto's thyroiditis.
AB  - T helper 17(Th17) cell is a new subset of CD4(+) T cells that produce a
      proinflammatory cytokine interleukin-17 (IL-17). Th17 cells have recently been
      shown to play a critical role in many autoimmune diseases that had previously
      been thought to be Th1 dominant. Although Hashimoto's thyroiditis (HT) was
      thought to be a Th1-type disease, the contributions of Th17 cells to the
      pathogenesis remain unclear. In this study, we investigated the expression levels
      of Th1/Th17 cell-associated factors in peripheral blood mononuclear cells (PBMC)
      and plasma from patients with HT by quantitative real-time polymerase chain
      reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA). Our results
      showed that the expression levels of Th1 cells-related T-bet and interferon-gamma
      (IFN-gamma) mRNA in PBMC from HT significantly decreased. However, the mRNA of
      Th17 coherent retinoic acid-related orphan nuclear receptor gamma t (RORgammat)
      and IL-17 in patients with HT increased. In addition, a negative correlation
      between T-bet and RORgammat mRNA expression was found in patients with HT, and
      the similar phenomena also appeared on the levels of mRNA and plasma
      concentration between IFN-gamma and IL-17. It suggested that Th17 cells rather
      than Th1 cells predominated among patients suffering from HT, and Th17 cells
      might be involved in the pathogenesis of HT.

PMID- 20696024
TI  - PTPN22 polymorphism is related to autoimmune disease risk in patients with Turner
      syndrome.
AB  - Individuals with Turner syndrome (TS) clearly have an increased risk for
      autoimmune diseases. Recently, an allelic variation (C1858T) of the PTPN22 gene
      was revealed to be associated with the development of autoimmunity. Thus, the aim
      of this study was to determine the frequency of the PTPN22 C1858T polymorphism in
      women with Turner syndrome (TS) compared to controls. Case-control study
      comprises 142 women with TS (cases) and 180 healthy and fertile women without a
      history of autoimmune disease (controls). Detection of the PTPN22 C1858T
      polymorphism (rs2476601) was performed by TaqMan real-time PCR. The chi-square
      test was used to compare allele and genotype frequencies between groups and to
      estimate the Hardy-Weinberg equilibrium. All P-values were two-tailed, and 95%
      confidence intervals (CIs) were calculated. A P-value <0.05 was considered
      statistically significant. Genotypes CC, CT and TT of the PTPN22 C1858T
      polymorphism presented frequencies of, respectively, 67.6%, 28.2% and 4.2% in the
      TS, and 82.8%, 16.1% and 1.1% in the control group (P = 0.0043). Alleles C and T
      were present in, respectively, 81.7% and 18.3% of the patients with TS (P =
      0.001, OR = 2.22, 95% CI = 1.39-3.54) and in 90.8% and 9.2%, respectively, of the
      controls. The data suggest that in Brazilian patients with TS, the PTPN22 C1858T
      polymorphism may be an important genetic factor predisposing to autoimmune
      disease risk.

PMID- 20696025
TI  - Differential activation of complement by apoptotic cells opsonized with anti-Ro60
      and anti-La autoantibodies.

PMID- 20696027
TI  - Role of MICA in the immune response to transplants.
AB  - Among the cell surface antigens that can elicit an immune response in transplant
      recipients MICA antigens occupy a special place. They are similar to human
      leukocyte antigens (HLAs) while being very different from them. They are not as
      polymorphic and their quantity is smaller. In consequence, the impact of MICA
      antigens in transplantation is not as dramatic. However, our early guess that
      these ligands of NKG2D could elicit antibodies and cell-mediated immunity has
      been definitely confirmed. Careful analysis with MICA transfectant cells, for
      absorption and elution, established the specificity of the epitopes involved.
      Typing of recipients and donors by sequencing the MICA alleles has established
      that de novo antibodies produced in kidney transplant recipients are directed at
      mismatched MICA epitopes and are associated with acute rejection and chronic
      transplant failure. Acute graft-versus-host disease was observed in stem cell
      recipients who were mismatched for MICA.

PMID- 20696028
TI  - Serotype specificity of antibodies against foot-and-mouth disease virus in cattle
      in selected districts in Uganda.
AB  - Uganda had an unusually large number of foot-and-mouth disease (FMD) outbreaks in
      2006, and all clinical reports were in cattle. A serological investigation was
      carried out to confirm circulating antibodies against foot-and-mouth disease
      virus (FMDV) by ELISA for antibodies against non-structural proteins and
      structural proteins. Three hundred and forty-nine cattle sera were collected from
      seven districts in Uganda, and 65% of these were found positive for antibodies
      against the non-structural proteins of FMDV. A subset of these samples were
      analysed for serotype specificity of the identified antibodies. High prevalences
      of antibodies against non-structural proteins and structural proteins of FMDV
      serotype O were demonstrated in herds with typical visible clinical signs of FMD,
      while prevalences were low in herds without clinical signs of FMD. Antibody
      titres were higher against serotype O than against serotypes SAT 1, SAT 2 and SAT
      3 in the sera investigated for serotype-specific antibodies. Only FMDV serotype O
      virus was isolated from one probang sample. This study shows that the majority of
      the FMD outbreaks in 2006 in the region studied were caused by FMDV serotype O;
      however, there was also evidence of antibodies to both SAT 1 and SAT 3 in one
      outbreak in a herd inside Queen Elizabeth national park area.

PMID- 20696029
TI  - Field Epidemiology Training Programmes in Africa - Where are the Graduates?
AB  - BACKGROUND: The current shortage of human resources for health threatens the
      attainment of the Millennium Development Goals. There is currently limited
      published evidence of health-related training programmes in Africa that have
      produced graduates, who remain and work in their countries after graduation.
      However, anecdotal evidence suggests that the majority of graduates of field
      epidemiology training programmes (FETPs) in Africa stay on to work in their home
      countries--many as valuable resources to overstretched health systems. METHODS:
      Alumni data from African FETPs were reviewed in order to establish graduate
      retention. Retention was defined as a graduate staying and working in their home
      country for at least 3 years after graduation. African FETPs are located in
      Burkina Faso, Ethiopia, Ghana, Kenya, Nigeria, Rwanda, South Africa, the United
      Republic of Tanzania, Uganda and Zimbabwe. However, this paper only includes the
      Uganda and Zimbabwe FETPs, as all the others are recent programmes. RESULTS: This
      review shows that enrolment increased over the years, and that there is high
      graduate retention, with 85.1% (223/261) of graduates working within country of
      training; most working with Ministries of Health (46.2%; 105/261) and non
      governmental organizations (17.5%; 40/261). Retention of graduates with a medical
      undergraduate degree was higher (Zimbabwe 80% [36/83]; Uganda 90.6% [125/178])
      than for those with other undergraduate qualifications (Zimbabwe 71.1% [27/83];
      Uganda 87.5% [35/178]). CONCLUSIONS: African FETPs have unique features which may
      explain their high retention of graduates. These include: programme ownership by
      ministries of health and local universities; well defined career paths;
      competence-based training coupled with a focus on field practice during training;
      awarding degrees upon completion; extensive training and research opportunities
      made available to graduates; and the social capital acquired during training.

PMID- 20696030
TI  - A process evaluation of a "physical activity pathway" in the primary care
      setting.
AB  - BACKGROUND: Let's Get Moving (LGM) is a systematic approach to integrating
      physical activity promotion into the primary care setting. LGM combines a number
      of recommended strategies to support behavior change including brief
      interventions, goal-setting, written resources, and follow-up support. This study
      involved a process evaluation of implementing LGM in UK general practice.
      METHODS: The LGM intervention was implemented in six general practices in London.
      Practices recruited patients either 'opportunistically' in routine consultations
      or by letter of invitation sent to patients on the hypertension disease register.
      A key component of the intervention was the delivery of a brief counselling
      session aimed at facilitating physical activity behaviour change. Data collection
      methods included electronic patient records, a practice survey and focus groups
      and interviews with practitioners. RESULTS: A total of 526 patients were
      considered for LGM, 378 via the 'opportunistic' recruitment method and 148 using
      the disease register approach. Patient interest in the brief counselling session
      was high although the actual delivery style and content varied between
      practitioners. Patients were directed towards a variety of physical activity
      opportunities including local leisure services and walking schemes. CONCLUSION:
      The learning from this pilot should inform a revised update of the LGM protocols
      before the planned dissemination of the intervention which is outlined in the
      Governments 'Be Active, Be Healthy' physical activity strategy. A robust
      assessment of effectiveness involving an experimental design and behaviour change
      measures is also warranted prior to wider dissemination.

PMID- 20696031
TI  - Secondary infection with Streptococcus suis serotype 7 increases the virulence of
      highly pathogenic porcine reproductive and respiratory syndrome virus in pigs.
AB  - BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) and
      Streptococcus suis are common pathogens in pigs. In samples collected during the
      porcine high fever syndrome (PHFS) outbreak in many parts of China, PRRSV and S.
      suis serotype 7 (SS7) have always been isolated together. To determine whether
      PRRSV-SS7 coinfection was the cause of the PHFS outbreak, we evaluated the
      pathogenicity of PRRSV and/or SS7 in a pig model of single and mixed infection.
      RESULTS: Respiratory disease, diarrhea, and anorexia were observed in all
      infected pigs. Signs of central nervous system (CNS) disease were observed in the
      highly pathogenic PRRSV (HP-PRRSV)-infected pigs (4/12) and the coinfected pigs
      (8/10); however, the symptoms of the coinfected pigs were clearly more severe
      than those of the HP-PRRSV-infected pigs. The mortality rate was significantly
      higher in the coinfected pigs (8/10) than in the HP-PRRSV- (2/12) and SS7
      infected pigs (0/10). The deceased pigs of the coinfected group had symptoms
      typical of PHFS, such as high fever, anorexia, and red coloration of the ears and
      the body. The isolation rates of HP-PRRSV and SS7 were higher and the lesion
      severity was greater in the coinfected pigs than in monoinfected pigs.
      CONCLUSION: HP-PRRSV infection increased susceptibility to SS7 infection, and
      coinfection of HP-PRRSV with SS7 significantly increased the pathogenicity of SS7
      to pigs.

PMID- 20696032
TI  - The Eat Smart Study: a randomised controlled trial of a reduced carbohydrate
      versus a low fat diet for weight loss in obese adolescents.
AB  - BACKGROUND: Despite the recognition of obesity in young people as a key health
      issue, there is limited evidence to inform health professionals regarding the
      most appropriate treatment options. The Eat Smart study aims to contribute to the
      knowledge base of effective dietary strategies for the clinical management of the
      obese adolescent and examine the cardiometablic effects of a reduced carbohydrate
      diet versus a low fat diet. METHODS AND DESIGN: Eat Smart is a randomised
      controlled trial and aims to recruit 100 adolescents over a 2 1/2 year period.
      Families will be invited to participate following referral by their health
      professional who has recommended weight management. Participants will be
      overweight as defined by a body mass index (BMI) greater than the 90th
      percentile, using CDC 2000 growth charts. An accredited 6-week psychological life
      skills program 'FRIENDS for Life', which is designed to provide behaviour change
      and coping skills will be undertaken prior to volunteers being randomised to
      group. The intervention arms include a structured reduced carbohydrate or a
      structured low fat dietary program based on an individualised energy
      prescription. The intervention will involve a series of dietetic appointments
      over 24 weeks. The control group will commence the dietary program of their
      choice after a 12 week period. Outcome measures will be assessed at baseline,
      week 12 and week 24. The primary outcome measure will be change in BMI z-score. A
      range of secondary outcome measures including body composition, lipid fractions,
      inflammatory markers, social and psychological measures will be measured.
      DISCUSSION: The chronic and difficult nature of treating the obese adolescent is
      increasingly recognised by clinicians and has highlighted the need for research
      aimed at providing effective intervention strategies, particularly for use in the
      tertiary setting. A structured reduced carbohydrate approach may provide a
      dietary pattern that some families will find more sustainable and effective than
      the conventional low fat dietary approach currently advocated. This study aims to
      investigate the acceptability and effectiveness of a structured reduced dietary
      carbohydrate intervention and will compare the outcomes of this approach with a
      structured low fat eating plan. TRIAL REGISTRATION: The protocol for this study
      is registered with the International Clinical Trials Registry (ISRCTN49438757).

PMID- 20696033
TI  - Identification of testis-relevant genes using in silico analysis from testis ESTs
      and cDNA microarray in the black tiger shrimp (Penaeus monodon).
AB  - BACKGROUND: Poor reproductive maturation of the black tiger shrimp (Penaeus
      monodon) in captivity is one of the serious threats to sustainability of the
      shrimp farming industry. Understanding molecular mechanisms governing
      reproductive maturation processes requires the fundamental knowledge of
      integrated expression profiles in gonads of this economically important species.
      In P. monodon, a non-model species for which the genome sequence is not
      available, expressed sequence tag (EST) and cDNA microarray analyses can help
      reveal important transcripts relevant to reproduction and facilitate functional
      characterization of transcripts with important roles in male reproductive
      development and maturation. RESULTS: In this study, a conventional testis EST
      library was exploited to reveal novel transcripts. A total of 4,803 ESTs were
      unidirectionally sequenced and analyzed in silico using a customizable data
      analysis package, ESTplus. After sequence assembly, 2,702 unique sequences
      comprised of 424 contigs and 2,278 singletons were identified; of these, 1,133
      sequences are homologous to genes with known functions. The sequences were
      further characterized according to gene ontology categories (41% biological
      process, 24% molecular function, 35% cellular component). Through comparison with
      EST libraries of other tissues of P. monodon, 1,579 transcripts found only in the
      testis cDNA library were identified. A total of 621 ESTs have not been identified
      in penaeid shrimp. Furthermore, cDNA microarray analysis revealed several ESTs
      homologous to testis-relevant genes were more preferentially expressed in testis
      than in ovary. Representatives of these transcripts, homologs of saposin (PmSap)
      and Dmc1 (PmDmc1), were further characterized by RACE-PCR. The more abundant
      expression levels in testis than ovary of PmSap and PmDmc1 were verified by
      quantitative real-time PCR in juveniles and wild broodstock of P. monodon.
      CONCLUSIONS: Without a genome sequence, a combination of EST analysis and high
      throughput cDNA microarray technology can be a useful integrated tool as an
      initial step towards the identification of transcripts with important biological
      functions. Identification and expression analysis of saposin and Dmc1 homologs
      demonstrate the power of these methods for characterizing functionally important
      genes in P. monodon.

PMID- 20696034
TI  - Compliance assessment of ambulatory Alzheimer patients to aid therapeutic
      decisions by healthcare professionals.
AB  - BACKGROUND: Compliance represents a major determinant for the effectiveness of
      pharmacotherapy. Compliance reports summarising electronically compiled
      compliance data qualify healthcare needs and can be utilised as part of a
      compliance enhancing intervention. Nevertheless, evidence-based information on a
      sufficient level of compliance is scarce complicating the interpretation of
      compliance reports. The purpose of our pilot study was to determine the
      compliance of ambulatory Alzheimer patients to antidementia drugs under routine
      therapeutic use using electronic monitoring. In addition, the forgiveness of
      donepezil (i.e. its ability to sustain adequate pharmacological response despite
      suboptimal compliance) was characterised and evidence-based guidance for the
      interpretation of compliance reports was intended to be developed. METHODS: We
      determined the compliance of four different antidementia drugs by electronic
      monitoring in 31 patients over six months. All patients were recruited from the
      gerontopsychiatric clinic of a university hospital as part of a pilot study. The
      so called medication event monitoring system (MEMS) was employed, consisting of a
      vial with a microprocessor in the lid which records the time (date, hour, minute)
      of every opening. Daily compliance served as primary outcome measure, defined as
      percentage of days with correctly administered doses of medication. In addition,
      pharmacokinetics and pharmacodynamics of donepezil were simulated to
      systematically assess therapeutic undersupply also incorporating study compliance
      patterns. Statistical analyses were performed with SPSS and Microsoft Excel.
      RESULTS: Median daily compliance was 94% (range 48%-99%). Ten patients (32%) were
      non-compliant at least for one month. One-sixth of patients taking donepezil
      displayed periods of therapeutic undersupply. For 10 mg and 5 mg donepezil once
      daily dosing, the estimated forgiveness of donepezil was 80% and 90% daily
      compliance or two and one dosage omissions at steady state, respectively. Based
      on the simulation findings we developed rules for the evidence-based
      interpretation of donepezil compliance reports. CONCLUSIONS: Compliance in
      ambulatory Alzheimer patients was for the first time assessed under routine
      conditions using electronic monitoring: On average compliance was relatively high
      but variable between patients. The approach of pharmacokinetic/pharmacodynamic in
      silico simulations was suitable to characterise the forgiveness of donepezil
      suggesting evidence-based recommendations for the interpretation of compliance
      reports.

PMID- 20696035
TI  - Delphi research exploring essential components and preconditions for case
      management in people with dementia.
AB  - BACKGROUND: Case management programmes for home-dwelling people with dementia and
      their informal carers exist in multiple forms and shapes. The aim of this
      research was to identify the essential components of case management for people
      with dementia as well as the preconditions for an effective delivery of case
      management services. METHOD: The method used to carry out the research was a
      modified four-phase Delphi design. First, a list of potentially essential
      components and preconditions for the provision of case management was drawn up on
      the basis of a literature review and a subsequent focus group interview. The list
      was then validated by experts in a first Delphi survey round, following which the
      researchers translated the list items into 75 statements. In the second Delphi
      survey, the experts rated the statements; in the third Delphi round, they rated
      18 statements on which no consensus had been reached in the second round.
      RESULTS: The experts were able to build consensus on 61 of the 75 statements.
      Essential components of case management for people with dementia are:
      information, support and counselling, coordination of the care provided and, to a
      lesser extent, practical help. A patient-centred approach was found to be one of
      the key aspects of providing case management services. Essential preconditions
      are: vision, care relationship, structured methodology, integration of case
      management into the health care chain, and the case manager's level of training
      and expertise. CONCLUSIONS: We recommend that, based on the essential components
      and preconditions referred to above, quality criteria be developed for the
      provision of case management for people with dementia. Furthermore, we suggest
      the conduct of additional research to assess the effectiveness of case management
      in people with dementia.

PMID- 20696036
TI  - FACT: functional annotation transfer between proteins with similar feature
      architectures.
AB  - BACKGROUND: The increasing number of sequenced genomes provides the basis for
      exploring the genetic and functional diversity within the tree of life. Only a
      tiny fraction of the encoded proteins undergoes a thorough experimental
      characterization. For the remainder, bioinformatics annotation tools are the only
      means to infer their function. Exploiting significant sequence similarities to
      already characterized proteins, commonly taken as evidence for homology, is the
      prevalent method to deduce functional equivalence. Such methods fail when
      homologs are too diverged, or when they have assumed a different function.
      Finally, due to convergent evolution, functional equivalence is not necessarily
      linked to common ancestry. Therefore complementary approaches are required to
      identify functional equivalents. RESULTS: We present the Feature Architecture
      Comparison Tool http://www.cibiv.at/FACT to search for functionally equivalent
      proteins. FACT uses the similarity between feature architectures of two proteins,
      i.e., the arrangements of functional domains, secondary structure elements and
      compositional properties, as a proxy for their functional equivalence. A scoring
      function measures feature architecture similarities, which enables searching for
      functional equivalents in entire proteomes. Our evaluation of 9,570 EC classified
      enzymes revealed that FACT, using the full feature, set outperformed the existing
      architecture-based approaches by identifying significantly more functional
      equivalents as highest scoring proteins. We show that FACT can identify
      functional equivalents that share no significant sequence similarity. However,
      when the highest scoring protein of FACT is also the protein with the highest
      local sequence similarity, it is in 99% of the cases functionally equivalent to
      the query. We demonstrate the versatility of FACT by identifying a missing link
      in the yeast glutathione metabolism and also by searching for the human GolgA5
      equivalent in Trypanosoma brucei. CONCLUSIONS: FACT facilitates a quick and
      sensitive search for functionally equivalent proteins in entire proteomes. FACT
      is complementary to approaches using sequence similarity to identify proteins
      with the same function. Thus, FACT is particularly useful when functional
      equivalents need to be identified in evolutionarily distant species, or when
      functional equivalents are not homologous. The most reliable annotation
      transfers, however, are achieved when feature architecture similarity and
      sequence similarity are jointly taken into account.

PMID- 20696037
TI  - Multiple distinct small RNAs originate from the same microRNA precursors.
AB  - BACKGROUND: MicroRNAs (miRNAs), which originate from precursor transcripts with
      stem-loop structures, are essential gene expression regulators in eukaryotes.
      RESULTS: We report 19 miRNA precursors in Arabidopsis that can yield multiple
      distinct miRNA-like RNAs in addition to miRNAs and miRNA*s. These miRNA precursor
      derived miRNA-like RNAs are often arranged in phase and form duplexes with an
      approximately two-nucleotide 3'-end overhang. Their production depends on the
      same biogenesis pathway as their sibling miRNAs and does not require RNA
      dependent RNA polymerases or RNA polymerase IV. These miRNA-like RNAs are
      methylated, and many of them are associated with Argonaute proteins. Some of the
      miRNA-like RNAs are differentially expressed in response to bacterial challenges,
      and some are more abundant than the cognate miRNAs. Computational and expression
      analyses demonstrate that some of these miRNA-like RNAs are potentially
      functional and they target protein-coding genes for silencing. The function of
      some of these miRNA-like RNAs was further supported by their target cleavage
      products from the published small RNA degradome data. Our systematic examination
      of public small-RNA deep sequencing data from four additional plant species
      (Oryza sativa, Physcomitrella patens, Medicago truncatula and Populus
      trichocarpa) and four animals (Homo sapiens, Mus musculus, Caenorhabditis elegans
      and Drosophila) shows that such miRNA-like RNAs exist broadly in eukaryotes.
      CONCLUSIONS: We demonstrate that multiple miRNAs could derive from miRNA
      precursors by sequential processing of Dicer or Dicer-like proteins. Our results
      suggest that the pool of miRNAs is larger than was previously recognized, and
      miRNA-mediated gene regulation may be broader and more complex than previously
      thought.

PMID- 20696038
TI  - Aberrant ERK 1/2 complex activation and localization in scrapie-infected GT1-1
      cells.
AB  - BACKGROUND: Fatal neurodegenerative disorders such as Creutzfeldt-Jakob and
      Gerstmann-Straussler-Scheinker diseases in humans, scrapie and bovine spongiform
      encephalopathy in animals, are characterized by the accumulation in the brain of
      a pathological form of the prion protein (PrP) denominated PrPSc. The latter
      derives from the host cellular form, PrPC, through a process whereby portions of
      its alpha-helical and coil structures are refolded into beta-sheet structures.
      RESULTS: In this work, the widely known in vitro model of prion replication,
      hypothalamic GT1-1 cell line, was used to investigate cellular and molecular
      responses to prion infection. The MAP kinase cascade was dissected to assess the
      phosphorylation levels of src, MEK 1/2 and ERK 1/2 signaling molecules, both
      before and after prion infection. Our findings suggest that prion replication
      leads to a hyper-activation of this pathway. Biochemical analysis was
      complemented with immunofluorescence studies to map the localization of the ERK
      complex within the different cellular compartments. We showed how the ERK complex
      relocates in the cytosol upon prion infection. We correlated these findings with
      an impairment of cell growth in prion-infected GT1-1 cells as probed by MTT
      assay. Furthermore, given the persistent urgency in finding compounds able to
      cure prion infected cells, we tested the effects on the ERK cascade of two
      molecules known to block prion replication in vitro, quinacrine and Fab D18. We
      were able to show that while these two compounds possess similar effects in
      curing prion infection, they affect the MAP kinase cascade differently.
      CONCLUSIONS: Taken together, our results help shed light on the molecular events
      involved in neurodegeneration and neuronal loss in prion infection and
      replication. In particular, the combination of chronic activation and aberrant
      localization of the ERK complex may lead to a lack of essential neuroprotective
      and survival factors. Interestingly, these data seem to define some common traits
      with other neurodegenerative disorders such as, for example, Alzheimer's disease.

PMID- 20696040
TI  - A descriptive study of a manual therapy intervention within a randomised
      controlled trial for hamstring and lower limb injury prevention.
AB  - BACKGROUND: There is little literature describing the use of manual therapy
      performed on athletes. It was our purpose to document the usage of a sports
      chiropractic manual therapy intervention within a RCT by identifying the type,
      amount, frequency, location and reason for treatment provided. This information
      is useful for the uptake of the intervention into clinical settings and to allow
      clinicians to better understand a role that sports chiropractors offer. METHODS:
      All treatment rendered to 29 semi-elite Australian Rules footballers in the
      sports chiropractic intervention group of an 8 month RCT investigating hamstring
      and lower-limb injury prevention was recorded. Treatment was pragmatically and
      individually determined and could consist of high-velocity, low-amplitude (HVLA)
      manipulation, mobilization and/or supporting soft tissue therapies. Descriptive
      statistics recorded the treatment rendered for symptomatic or asymptomatic
      benefit, delivered to joint or soft tissue structures and categorized into body
      regions. For the joint therapy, it was recorded whether treatment consisted of
      HVLA manipulation, HVLA manipulation and mobilization, or mobilization only.
      Breakdown of the HVLA technique was performed. RESULTS: A total of 487 treatments
      were provided (mean 16.8 consultations/player) with 64% of treatment for
      asymptomatic benefit (73% joint therapies, 57% soft tissue therapies). Treatment
      was delivered to approximately 4 soft tissue and 4 joint regions each
      consultation. The most common asymptomatic regions treated with joint therapies
      were thoracic (22%), knee (20%), hip (19%), sacroiliac joint (13%) and lumbar
      (11%). For soft tissue therapies it was gluteal (22%), hip flexor (14%), knee
      (12%) and lumbar (11%). The most common symptomatic regions treated with joint
      therapies were lumbar (25%), thoracic (15%) and hip (14%). For soft tissue
      therapies it was gluteal (22%), lumbar (15%) and posterior thigh (8%). Of the
      joint therapy, 56% was HVLA manipulation only, 36% high-HVLA and mobilization and
      9% mobilization only. Of the HVLA manipulation, 63% was manually performed and
      37% mechanically assisted. CONCLUSIONS: The intervention applied was multimodal
      and multi-regional. Most treatment was for asymptomatic benefit, particularly for
      joint based therapies, which consisted largely of HVLA manipulation techniques.
      Most treatment was applied to non-local hamstring structures, in particular the
      knee, hip, pelvis and spine.

PMID- 20696039
TI  - Frequent associations between CTL and T-Helper epitopes in HIV-1 genomes and
      implications for multi-epitope vaccine designs.
AB  - BACKGROUND: Epitope vaccines have been suggested as a strategy to counteract
      viral escape and development of drug resistance. Multiple studies have shown that
      Cytotoxic T-Lymphocyte (CTL) and T-Helper (Th) epitopes can generate strong
      immune responses in Human Immunodeficiency Virus (HIV-1). However, not much is
      known about the relationship among different types of HIV epitopes, particularly
      those epitopes that can be considered potential candidates for inclusion in the
      multi-epitope vaccines. RESULTS: In this study we used association rule mining to
      examine relationship between different types of epitopes (CTL, Th and antibody
      epitopes) from nine protein-coding HIV-1 genes to identify strong associations as
      potent multi-epitope vaccine candidates. Our results revealed 137 association
      rules that were consistently present in the majority of reference and non
      reference HIV-1 genomes and included epitopes of two different types (CTL and Th)
      from three different genes (Gag, Pol and Nef). These rules involved 14 non
      overlapping epitope regions that frequently co-occurred despite high mutation and
      recombination rates, including in genomes of circulating recombinant forms. These
      epitope regions were also highly conserved at both the amino acid and nucleotide
      levels indicating strong purifying selection driven by functional and/or
      structural constraints and hence, the diminished likelihood of successful escape
      mutations. CONCLUSIONS: Our results provide a comprehensive systematic survey of
      CTL, Th and Ab epitopes that are both highly conserved and co-occur together
      among all subtypes of HIV-1, including circulating recombinant forms. Several co
      occurring epitope combinations were identified as potent candidates for inclusion
      in multi-epitope vaccines, including epitopes that are immuno-responsive to
      different arms of the host immune machinery and can enable stronger and more
      efficient immune responses, similar to responses achieved with adjuvant
      therapies. Signature of strong purifying selection acting at the nucleotide level
      of the associated epitopes indicates that these regions are functionally
      critical, although the exact reasons behind such sequence conservation remain to
      be elucidated.

PMID- 20696041
TI  - Clinico-epidemiological profile and diagnostic procedures of pediatric
      tuberculosis in a tertiary care hospital of western Nepal-a case-series analysis.
AB  - BACKGROUND: Changing epidemiology and diagnostic difficulties of paediatric
      tuberculosis (TB) are being increasingly reported. Our aim was to describe
      clinico-epidemiological profile and diagnostic procedures used for paediatric TB.
      METHODS: A retrospective case-series analysis was carried out in a tertiary care
      teaching hospital of western Nepal. All pediatric TB (age 0-14 years) patients
      registered in DOTS clinic during the time period from March, 2003 to July, 2008
      were included. Medical case files were reviewed for information on demography,
      clinical findings, investigations and final diagnosis. Analysis was done on SPSS
      package. Results were expressed as rates and proportions. Chi square test was
      used to test for statistical significance. RESULTS: About 17.2% (162/941) of TB
      patients were children. Common symptoms were cough, fever and lymph node
      swelling. The types of TB were pulmonary TB (46.3%, 75/162), followed by extra
      pulmonary TB (41.4%, 67/162). Twelve patients (7.4%) had disseminated TB.
      Distribution of types of TB according to gender was similar. PTB was common in
      younger age than EPTB which was statistically significant. EPTB was mainly
      localized to lymph node (38, 50.7%), and abdomen (9, 12%). Five main
      investigations namely Mantoux test, BCG test, chest radiograph, erythrocyte
      sedimentation rate (ESR) and fine needle aspiration cytology (FNAC) or biopsy
      were carried out to diagnose TB. CONCLUSIONS: Paediatric TB in both pulmonary and
      extrapulmonary forms is a common occurrence in our setting. Age incidence
      according to type of TB was significant. Diagnosis was based on a combination of
      epidemiological and clinical suspicion supported by results of various
      investigations.

PMID- 20696042
TI  - What are the important components of the clinical assessment of hand problems in
      older adults in primary care? Results of a Delphi study.
AB  - BACKGROUND: To identify clinical questions and assessments regarded by health
      care practitioners as important when assessing undifferentiated hand pain or
      problems in adults aged 50 years and over presenting to primary care. METHODS: A
      purposively selected panel of 26 UK-based Health Care Practitioners comprising
      occupational therapists, physiotherapists, rheumatologists and general
      practitioners, were invited to take part in a consensus study involving three
      postal rounds of a Delphi questionnaire with accompanying case scenarios.
      Participants were asked to generate questions and assessments (round 1), rate
      their importance (round 2), and vote on which items were most important (round
      3). RESULTS: Sixteen Health Care Practitioners agreed to participate with 11
      completing all three rounds. The first round of the Delphi study generated 156
      questions and 143 assessments. After three rounds agreement was reached on the
      importance of 25 questions and 19 assessments. Questions were weighted towards
      current symptoms, but also included the history of previous hand problems, self
      reported hand function, co-morbidity and general health. Observation and
      palpation of features predominated in the choice of assessment, but specific
      tests, grip strength, evaluation of sensation and hand function were also
      included. CONCLUSIONS: A pool of clinical questions and assessments were
      generated by Health Care Practitioners, and those considered most important for
      assessing older adults presenting with undifferentiated hand pain and hand
      problems in primary care were identified. Further evaluation is required to
      establish the reliability and feasibility of using these questions and
      assessments in primary care. In particular, the relative contribution of these
      questions and assessments in evaluating the nature and severity of hand problems,
      assisting diagnosis, indicating appropriate management, and predicting future
      course requires further investigation.

PMID- 20696043
TI  - Replication of the association of chromosomal region 9p21.3 with generalized
      aggressive periodontitis (gAgP) using an independent case-control cohort.
AB  - BACKGROUND: The human chromosomal region 9p21.3 has been shown to be strongly
      associated with Coronary Heart Disease (CHD) in several Genome-wide Association
      Studies (GWAS). Recently, this region has also been shown to be associated with
      Aggressive Periodontitis (AgP), strengthening the hypothesis that the established
      epidemiological association between periodontitis and CHD is caused by a shared
      genetic background, in addition to common environmental and behavioural risk
      factors. However, the size of the analyzed cohorts in this primary analysis was
      small compared to other association studies on complex diseases. Using our own
      AgP cohort, we attempted to confirm the described associations for the
      chromosomal region 9p21.3. METHODS: We analyzed our cohort consisting of patients
      suffering from the most severe form of AgP, generalized AgP (gAgP) (n = 130) and
      appropriate periodontally healthy control individuals (n = 339) by genotyping
      four tagging SNPs (rs2891168, rs1333042, rs1333048 and rs496892), located in the
      chromosomal region 9p21.3, that have been associated with AgP. RESULTS: The
      results confirmed significant associations between three of the four SNPs and
      gAgP. The combination of our results with those from the study which described
      this association for the first time in a meta-analysis of the four tagging SNPs
      produced clearly lower p-values compared with the results of each individual
      study. According to these results, the most plausible genetic model for the
      association of all four tested SNPs with gAgP seems to be the multiplicative one.
      CONCLUSION: We positively replicated the finding of an association between the
      chromosomal region 9p21.3 and gAgP. This result strengthens support for the
      hypothesis that shared susceptibility genes within this chromosomal locus might
      be involved in the pathogenesis of both CHD and gAgP.

PMID- 20696044
TI  - Genetic variations of nucleoprotein gene of influenza A viruses isolated from
      swine in Thailand.
AB  - BACKGROUND: Influenza A virus causes severe disease in both humans and animals
      and thus, has a considerably impact on economy and public health. In this study,
      the genetic variations of the nucleoprotein (NP) gene of influenza viruses
      recovered from swine in Thailand were determined. RESULTS: Twelve influenza A
      virus specimens were isolated from Thai swine. All samples were subjected to
      nucleotide sequencing of the complete NP gene. Phylogenetic analysis was
      conducted by comparing the NP gene of swine influenza viruses with that of
      seasonal and pandemic human viruses and highly pathogenic avian viruses from
      Thailand (n = 77). Phylogenetic analysis showed that the NP gene from different
      host species clustered in distinct host specific lineages. The NP gene of swine
      influenza viruses clustered in either Eurasian swine or Classical swine lineages.
      Genetic analysis of the NP gene suggested that swine influenza viruses
      circulating in Thailand display 4 amino acids unique to Eurasian and Classical
      swine lineages. In addition, the result showed 1 and 5 amino acids unique to
      avian and human lineages, respectively. Furthermore, nucleotide substitution
      rates showed that the NP gene is highly conserved especially in avian influenza
      viruses. CONCLUSION: The NP gene sequence of influenza A in Thailand is highly
      conserved within host-specific lineages and shows amino acids potentially unique
      to distinct NP lineages. This information can be used to investigate potential
      interspecies transmission of influenza A viruses. In addition, the genetic
      variations of the NP gene will be useful for monitoring the viruses and preparing
      effective prevention and control strategies for potentially pandemic influenza
      outbreaks.

PMID- 20696045
TI  - Role of COX-2 in cough reflex sensitivity to inhaled capsaicin in patients with
      sinobronchial syndrome.
AB  - BACKGROUND: Sinobronchial syndrome is a cause of chronic productive cough.
      Inflammatory mediators are involved in the pathophysiology of chronic productive
      cough. Accumulating evidences indicate that cyclooxygenase (COX)-2, one of the
      inducible isoforms of COX, is a key element in the pathophysiological process of
      a number of inflammatory disorders. However, little is known about the role of
      COX-2 in chronic productive cough in patients with sinobronchial syndrome known
      as neutrophilic bronchial inflammation. METHODS: The effect of etodolac, a potent
      COX-2 inhibitor, on cough response to inhaled capsaicin was examined in 15
      patients with sinobronchial syndrome in a randomized, placebo-controlled cross
      over study. Capsaicin cough threshold, defined as the lowest concentration of
      capsaicin eliciting five or more coughs, was measured as an index of airway cough
      reflex sensitivity. RESULTS: The cough threshold was significantly (p < 0.03)
      increased after two-week treatment with etodolac (200 mg twice a day orally)
      compared with placebo [37.5 (GSEM 1.3) vs. 27.2 (GSEM 1.3) muM]. CONCLUSIONS:
      These findings indicate that COX-2 may be a possible modulator augmenting airway
      cough reflex sensitivity in patients with sinobronchial syndrome.

PMID- 20696046
TI  - eGIFT: mining gene information from the literature.
AB  - BACKGROUND: With the biomedical literature continually expanding, searching
      PubMed for information about specific genes becomes increasingly difficult. Not
      only can thousands of results be returned, but gene name ambiguity leads to many
      irrelevant hits. As a result, it is difficult for life scientists and gene
      curators to rapidly get an overall picture about a specific gene from documents
      that mention its names and synonyms. RESULTS: In this paper, we present eGIFT
      (http://biotm.cis.udel.edu/eGIFT), a web-based tool that associates informative
      terms, called iTerms, and sentences containing them, with genes. To associate
      iTerms with a gene, eGIFT ranks iTerms about the gene, based on a score which
      compares the frequency of occurrence of a term in the gene's literature to its
      frequency of occurrence in documents about genes in general. To retrieve a gene's
      documents (Medline abstracts), eGIFT considers all gene names, aliases, and
      synonyms. Since many of the gene names can be ambiguous, eGIFT applies a
      disambiguation step to remove matches that do not correspond to this gene.
      Another additional filtering process is applied to retain those abstracts that
      focus on the gene rather than mention it in passing. eGIFT's information for a
      gene is pre-computed and users of eGIFT can search for genes by using a name or
      an EntrezGene identifier. iTerms are grouped into different categories to
      facilitate a quick inspection. eGIFT also links an iTerm to sentences mentioning
      the term to allow users to see the relation between the iTerm and the gene. We
      evaluated the precision and recall of eGIFT's iTerms for 40 genes; between 88%
      and 94% of the iTerms were marked as salient by our evaluators, and 94% of the
      UniProtKB keywords for these genes were also identified by eGIFT as iTerms.
      CONCLUSIONS: Our evaluations suggest that iTerms capture highly-relevant aspects
      of genes. Furthermore, by showing sentences containing these terms, eGIFT can
      provide a quick description of a specific gene. eGIFT helps not only life
      scientists survey results of high-throughput experiments, but also annotators to
      find articles describing gene aspects and functions.

PMID- 20696047
TI  - Protocol for Past BP: a randomised controlled trial of different blood pressure
      targets for people with a history of stroke of transient ischaemic attack (TIA)
      in primary care.
AB  - BACKGROUND: Blood pressure (BP) lowering in people who have had a stroke or
      transient ischaemic attack (TIA) leads to reduced risk of further stroke.
      However, it is not clear what the target BP should be, since intensification of
      therapy may lead to additional adverse effects. PAST BP will determine whether
      more intensive BP targets can be achieved in a primary care setting, and whether
      more intensive therapy is associated with adverse effects on quality of life.
      METHODS/DESIGN: This is a randomised controlled trial (RCT) in patients with a
      past history of stroke or TIA. Patients will be randomised to two groups and will
      either have their blood pressure (BP) lowered intensively to a target of 130 mmHg
      systolic, (or by 10 mmHg if the baseline systolic pressure is between 125 and 140
      mmHg) compared to a standard group where the BP will be reduced to a target of
      140 mmHg systolic. Patients will be managed by their practice at 1-3 month
      intervals depending on level of BP and followed-up by the research team at six
      monthly intervals for 12 months.610 patients will be recruited from approximately
      50 general practices. The following exclusion criteria will be applied: systolic
      BP <125 mmHg at baseline, 3 or more anti-hypertensive agents, orthostatic
      hypotension, diabetes mellitus with microalbuminuria or other condition requiring
      a lower treatment target or terminal illness.The primary outcome will be change
      in systolic BP over twelve months. Secondary outcomes include quality of life,
      adverse events and cardiovascular events.In-depth interviews with 30 patients and
      20 health care practitioners will be undertaken to investigate patient and
      healthcare professionals understanding and views of BP management. DISCUSSION:
      The results of this trial will inform whether intensive blood pressure targets
      can be achieved in people who have had a stroke or TIA in primary care, and help
      determine whether or not further research is required before recommending such
      targets for this population. TRIAL REGISTRATION: ISRCTN29062286.

PMID- 20696048
TI  - Association of HPA axis-related genetic variation with stress reactivity and
      aggressive behaviour in pigs.
AB  - BACKGROUND: Stress, elicited for example by aggressive interactions, has negative
      effects on various biological functions including immune defence, reproduction,
      growth, and, in livestock, on product quality. Stress response and aggressiveness
      are mutually interrelated and show large interindividual variation, partly
      attributable to genetic factors. In the pig little is known about the molecular
      genetic background of the variation in stress responsiveness and aggressiveness.
      To identify candidate genes we analyzed association of DNA markers in each of ten
      genes (CRH g.233C>T, CRHR1 c.*866_867insA, CRHBP c.51G>A, POMC c.293_298del, MC2R
      c.306T>G, NR3C1 c.*2122A>G, AVP c.207A>G, AVPR1B c.1084A>G, UCN g.1329T>C, CRHR2
      c.*13T>C) related to the hypothalamic-pituitary-adrenocortical (HPA) axis, one of
      the main stress-response systems, with various stress- and aggression-related
      parameters at slaughter. These parameters were: physiological measures of the
      stress response (plasma concentrations of cortisol, creatine kinase, glucose, and
      lactate), adrenal weight (which is a parameter reflecting activity of the central
      branch of the HPA axis over time) and aggressive behaviour (measured by means of
      lesion scoring) in the context of psychosocial stress of mixing individuals with
      different aggressive temperament. RESULTS: The SNP NR3C1 c.*2122A>G showed
      association with cortisol concentration (p = 0.024), adrenal weight (p = 0.003)
      and aggressive behaviour (front lesion score, p = 0.012; total lesion score p =
      0.045). The SNP AVPR1B c.1084A>G showed a highly significant association with
      aggressive behaviour (middle lesion score, p = 0.007; total lesion score p =
      0.003). The SNP UCN g.1329T>C showed association with adrenal weight (p = 0.019)
      and aggressive behaviour (front lesion score, p = 0.029). The SNP CRH g.233C>T
      showed a significant association with glucose concentration (p = 0.002), and the
      polymorphisms POMC c.293_298del and MC2R c.306T>G with adrenal weight (p = 0.027
      and p < 0.0001 respectively). CONCLUSIONS: The multiple and consistent
      associations shown by SNP in NR3C1 and AVPR1B provide convincing evidence for
      genuine effects of their DNA sequence variation on stress responsiveness and
      aggressive behaviour. Identification of the causal functional molecular
      polymorphisms would not only provide markers useful for pig breeding but also
      insight into the molecular bases of the stress response and aggressive behaviour
      in general.

PMID- 20696049
TI  - TAM: a method for enrichment and depletion analysis of a microRNA category in a
      list of microRNAs.
AB  - BACKGROUND: MicroRNAs (miRNAs) are a class of important gene regulators. The
      number of identified miRNAs has been increasing dramatically in recent years. An
      emerging major challenge is the interpretation of the genome-scale miRNA
      datasets, including those derived from microarray and deep-sequencing. It is
      interesting and important to know the common rules or patterns behind a list of
      miRNAs, (i.e. the deregulated miRNAs resulted from an experiment of miRNA
      microarray or deep-sequencing). RESULTS: For the above purpose, this study
      presents a method and develops a tool (TAM) for annotations of meaningful human
      miRNAs categories. We first integrated miRNAs into various meaningful categories
      according to prior knowledge, such as miRNA family, miRNA cluster, miRNA
      function, miRNA associated diseases, and tissue specificity. Using TAM, given
      lists of miRNAs can be rapidly annotated and summarized according to the
      integrated miRNA categorical data. Moreover, given a list of miRNAs, TAM can be
      used to predict novel related miRNAs. Finally, we confirmed the usefulness and
      reliability of TAM by applying it to deregulated miRNAs in acute myocardial
      infarction (AMI) from two independent experiments. CONCLUSION: TAM can
      efficiently identify meaningful categories for given miRNAs. In addition, TAM can
      be used to identify novel miRNA biomarkers. TAM tool, source codes, and miRNA
      category data are freely available at http://cmbi.bjmu.edu.cn/tam.

PMID- 20696050
TI  - An improved classification of G-protein-coupled receptors using sequence-derived
      features.
AB  - BACKGROUND: G-protein-coupled receptors (GPCRs) play a key role in diverse
      physiological processes and are the targets of almost two-thirds of the marketed
      drugs. The 3 D structures of GPCRs are largely unavailable; however, a large
      number of GPCR primary sequences are known. To facilitate the identification and
      characterization of novel receptors, it is therefore very valuable to develop a
      computational method to accurately predict GPCRs from the protein primary
      sequences. RESULTS: We propose a new method called PCA-GPCR, to predict GPCRs
      using a comprehensive set of 1497 sequence-derived features. The principal
      component analysis is first employed to reduce the dimension of the feature space
      to 32. Then, the resulting 32-dimensional feature vectors are fed into a simple
      yet powerful classification algorithm, called intimate sorting, to predict GPCRs
      at five levels. The prediction at the first level determines whether a protein is
      a GPCR or a non-GPCR. If it is predicted to be a GPCR, then it will be further
      predicted into certain family, subfamily, sub-subfamily and subtype by the
      classifiers at the second, third, fourth, and fifth levels, respectively. To
      train the classifiers applied at five levels, a non-redundant dataset is
      carefully constructed, which contains 3178, 1589, 4772, 4924, and 2741 protein
      sequences at the respective levels. Jackknife tests on this training dataset show
      that the overall accuracies of PCA-GPCR at five levels (from the first to the
      fifth) can achieve up to 99.5%, 88.8%, 80.47%, 80.3%, and 92.34%, respectively.
      We further perform predictions on a dataset of 1238 GPCRs at the second level,
      and on another two datasets of 167 and 566 GPCRs respectively at the fourth
      level. The overall prediction accuracies of our method are consistently higher
      than those of the existing methods to be compared. CONCLUSIONS: The comprehensive
      set of 1497 features is believed to be capable of capturing information about
      amino acid composition, sequence order as well as various physicochemical
      properties of proteins. Therefore, high accuracies are achieved when predicting
      GPCRs at all the five levels with our proposed method.

PMID- 20696051
TI  - Multi-locus analysis of human infective Cryptosporidium species and subtypes
      using ten novel genetic loci.
AB  - BACKGROUND: Cryptosporidium is a protozoan parasite that causes diarrheal illness
      in a wide range of hosts including humans. Two species, C. parvum and C. hominis
      are of primary public health relevance. Genome sequences of these two species are
      available and show only 3-5% sequence divergence. We investigated this sequence
      variability, which could correspond either to sequence gaps in the published
      genome sequences or to the presence of species-specific genes. Comparative
      genomic tools were used to identify putative species-specific genes and a subset
      of these genes was tested by PCR in a collection of Cryptosporidium clinical
      isolates and reference strains. RESULTS: The majority of the putative species
      specific genes examined were in fact common to C. parvum and C. hominis. PCR
      product sequence analysis revealed interesting SNPs, the majority of which were
      species-specific. These genetic loci allowed us to construct a robust and multi
      locus analysis. The Neighbour-Joining phylogenetic tree constructed clearly
      discriminated the previously described lineages of Cryptosporidium species and
      subtypes. CONCLUSIONS: Most of the genes identified as being species specific
      during bioinformatics in Cryptosporidium sp. are in fact present in multiple
      species and only appear species specific because of gaps in published genome
      sequences. Nevertheless SNPs may offer a promising approach to studying the
      taxonomy of closely related species of Cryptosporidia.

PMID- 20696052
TI  - Mutations in the WTX-gene are found in some high-grade microsatellite instable
      (MSI-H) colorectal cancers.
AB  - BACKGROUND: Genetically, colorectal cancers (CRCs) can be subdivided into tumors
      with chromosomal instability (CIN) or microsatellite instability (MSI). In both
      types of CRCs genes that are involved in the degradation of beta-CATENIN are
      frequently mutated. Whereas in CIN CRCs APC (Adenomatous Polyposis Coli) is
      affected in most cases, high grade MSI (MSI-H) CRCs frequently display mutations
      in various genes, like the APC-, AXIN2- or CTNNBI (beta-CATENIN) gene itself.
      Recently in Wilms tumors, WTX (Wilms tumor gene on the X-chromosome) was
      discovered as another gene involved in the destruction of beta-CATENIN. As the
      WTX-gene harbors a short T6-microsatellite in its N-terminal coding region, we
      hypothesized that frameshift-mutations might occur in MSI-H CRCs in the WTX gene,
      thus additionally contributing to the stabilization of beta-CATENIN in human
      CRCs. METHODS: DNA was extracted from 632 formalin-fixed, paraffin-embedded
      metastatic CRCs (UICCIV) and analyzed for MSI-H by investigating the stability of
      the highly sensitive microsatellite markers BAT25 and BAT26 applying fluorescence
      capillary electrophoresis (FCE). Then, in the MSI-H cases, well described
      mutational hot spot regions from the APC-, AXIN2- and CTNNBI genes were analyzed
      for genomic alterations by didesoxy-sequencing while the WTX T6-microsatellite
      was analyzed by fragment analysis. Additionally, the PCR products of T5-repeats
      were subcloned and mutations were validated using didesoxy-sequencing.
      Furthermore, the KRAS and the BRAF proto-oncogenes were analyzed for the most
      common activating mutations applying pyro-sequencing. mRNA expression of WTX from
      MSI-H and MSS cases and a panel of colorectal cancer cell lines was investigated
      using reverse transcription (RT-) PCR and FCE. RESULTS: In our cohort of 632
      metastatic CRCs (UICCIV) we identified 41 MSI-H cases (6.5%). Two of the 41 MSI-H
      cases (4.8%) displayed a frameshift mutation in the T6-repeat resulting in a T5
      sequence. Only one case, a male patient, expressed the mutated WTX gene while
      being wild type for all other investigated genes. CONCLUSION: Mutations in the
      WTX-gene might compromise the function of the beta-CATENIN destruction complex in
      only a small fraction of MSI-H CRCs thus contributing to the process of
      carcinogenesis.

PMID- 20696053
TI  - Integrative multicellular biological modeling: a case study of 3D epidermal
      development using GPU algorithms.
AB  - BACKGROUND: Simulation of sophisticated biological models requires considerable
      computational power. These models typically integrate together numerous
      biological phenomena such as spatially-explicit heterogeneous cells, cell-cell
      interactions, cell-environment interactions and intracellular gene networks. The
      recent advent of programming for graphical processing units (GPU) opens up the
      possibility of developing more integrative, detailed and predictive biological
      models while at the same time decreasing the computational cost to simulate those
      models. RESULTS: We construct a 3D model of epidermal development and provide a
      set of GPU algorithms that executes significantly faster than sequential central
      processing unit (CPU) code. We provide a parallel implementation of the
      subcellular element method for individual cells residing in a lattice-free
      spatial environment. Each cell in our epidermal model includes an internal gene
      network, which integrates cellular interaction of Notch signaling together with
      environmental interaction of basement membrane adhesion, to specify cellular
      state and behaviors such as growth and division. We take a pedagogical approach
      to describing how modeling methods are efficiently implemented on the GPU
      including memory layout of data structures and functional decomposition. We
      discuss various programmatic issues and provide a set of design guidelines for
      GPU programming that are instructive to avoid common pitfalls as well as to
      extract performance from the GPU architecture. CONCLUSIONS: We demonstrate that
      GPU algorithms represent a significant technological advance for the simulation
      of complex biological models. We further demonstrate with our epidermal model
      that the integration of multiple complex modeling methods for heterogeneous
      multicellular biological processes is both feasible and computationally tractable
      using this new technology. We hope that the provided algorithms and source code
      will be a starting point for modelers to develop their own GPU implementations,
      and encourage others to implement their modeling methods on the GPU and to make
      that code available to the wider community.

PMID- 20696054
TI  - Evolution of an adenocarcinoma in response to selection by targeted kinase
      inhibitors.
AB  - BACKGROUND: Adenocarcinomas of the tongue are rare and represent the minority (20
      to 25%) of salivary gland tumors affecting the tongue. We investigated the
      utility of massively parallel sequencing to characterize an adenocarcinoma of the
      tongue, before and after treatment. RESULTS: In the pre-treatment tumor we
      identified 7,629 genes within regions of copy number gain. There were 1,078 genes
      that exhibited increased expression relative to the blood and unrelated tumors
      and four genes contained somatic protein-coding mutations. Our analysis suggested
      the tumor cells were driven by the RET oncogene. Genes whose protein products are
      targeted by the RET inhibitors sunitinib and sorafenib correlated with being
      amplified and or highly expressed. Consistent with our observations,
      administration of sunitinib was associated with stable disease lasting 4 months,
      after which the lung lesions began to grow. Administration of sorafenib and
      sulindac provided disease stabilization for an additional 3 months after which
      the cancer progressed and new lesions appeared. A recurring metastasis possessed
      7,288 genes within copy number amplicons, 385 genes exhibiting increased
      expression relative to other tumors and 9 new somatic protein coding mutations.
      The observed mutations and amplifications were consistent with therapeutic
      resistance arising through activation of the MAPK and AKT pathways. CONCLUSIONS:
      We conclude that complete genomic characterization of a rare tumor has the
      potential to aid in clinical decision making and identifying therapeutic
      approaches where no established treatment protocols exist. These results also
      provide direct in vivo genomic evidence for mutational evolution within a tumor
      under drug selection and potential mechanisms of drug resistance accrual.

PMID- 20696055
TI  - Age- and sex-specific prevalence and ten-year risk for cardiovascular disease of
      all 16 risk factor combinations of the metabolic syndrome - A cross-sectional
      study.
AB  - BACKGROUND: Based on the AHA/NHLBI-definition three out of five cardiometabolic
      traits must be present for the diagnosis of the metabolic syndrome (MetS),
      resulting in 16 different combination types. The associated cardiovascular risk
      may however be different and specific combination may be indicative of an
      increased risk, furthermore little is known to which extent these 16 combinations
      contribute to the overall prevalence of MetS. Here we assessed the prevalence of
      all 16 combination types of MetS, analyzed the impact of age and gender on
      prevalence rates, and estimated the 10-year risk of fatal and non-fatal
      myocardial infarction (MI) of each MetS combination type. METHODS: We used data
      of the German Metabolic and Cardiovascular Risk Project (GEMCAS), a cross
      sectional study, performed during October 2005, including 35,869 participants
      (aged 18-99 years, 61% women). Age-standardized prevalence and 10-year PROCAM and
      ESC risk scores for MI were calculated. RESULTS: In both men and women the
      combination with elevated waist-circumference, blood pressure and glucose (WC-BP
      GL) was the most frequent combination (28%), however a distinct unequal
      distribution was observed regarding age and sex. Any combination with GL was
      common in the elderly, whereas any combination with dyslipidemia and without GL
      was frequent in the younger. Men without MetS had an estimated mean 10-year risk
      of 4.7% (95%-CI: 4.5%-4.8%) for MI (PROCAM), whereas the mean 10-year risk of men
      with MetS was clearly higher (age-standardized 7.9%; 7.8-8.0%). In women without
      MetS the mean 10-year risk for MI was 1.1%, in those with MetS 2.3%. The highest
      impact on an estimated 10-year risk for MI (PROCAM) was observed with TG-HDL-GL
      BP in both sexes (men 14.7%, women 3.9%). However, we could identify combinations
      with equal risks of non-fatal and fatal MI compared to participants without MetS.
      CONCLUSIONS: We observed large variations in the prevalence of all 16 combination
      types and their association to cardiovascular risk. The importance of different
      combinations of MetS changes with age and between genders putting emphasis on a
      tailored approach towards very young or very old subjects. This knowledge may
      guide clinicians to effectively screen individuals and prioritize diagnostic
      procedures depending on age and gender.

PMID- 20696056
TI  - Immunoglobulin GM 3 23 5,13,14 phenotype is strongly associated with IgG1
      antibody responses to Plasmodium vivax vaccine candidate antigens PvMSP1-19 and
      PvAMA-1.
AB  - BACKGROUND: Humoral immune responses play a key role in the development of
      immunity to malaria, but the host genetic factors that contribute to the
      naturally occurring immune responses to malarial antigens are not completely
      understood. The aim of the present investigation was to determine whether, in
      subjects exposed to malaria, GM and KM allotypes--genetic markers of
      immunoglobulin gamma and kappa-type light chains, respectively--contribute to the
      magnitude of natural antibody responses to target antigens that are leading
      vaccine candidates for protection against Plasmodium vivax. METHODS: Sera from
      210 adults, who had been exposed to malaria transmission in the Brazilian Amazon
      endemic area, were allotyped for several GM and KM determinants by a standard
      hemagglutination-inhibition method. IgG subclass antibodies to P. vivax apical
      membrane antigen 1 (PvAMA-1) and merozoite surface protein 1 (PvMSP1-19) were
      determined by an enzyme-linked immunosorbent assay. Multiple linear regression
      models and the non-parametric Mann-Whitney test were used for data analyses.
      RESULTS: IgG1 antibody levels to both PvMSP1-19 and PvAMA-1 antigens were
      significantly higher (P = 0.004, P = 0.002, respectively) in subjects with the GM
      3 23 5,13,14 phenotype than in those who lacked this phenotype. CONCLUSIONS:
      Results presented here show that immunoglobulin GM allotypes contribute to the
      natural antibody responses to P. vivax malaria antigens. These findings have
      important implications for the effectiveness of vaccines containing PvAMA-1 or
      PvMSP1-19 antigens. They also shed light on the possible role of malaria as one
      of the evolutionary selective forces that may have contributed to the maintenance
      of the extensive polymorphism at the GM loci.

PMID- 20696058
TI  - Recurrent retroperitoneal Schwannomas displaying different differentiation from
      primary tumor: case report and literature review.
AB  - BACKGROUND: Retroperitoneal Schwannomas are uncommonly found in the
      retroperitoneum and few of them show malignant transformation and invasion. Local
      recurrence are common in malignant Schwannomas with very few reports of tumor
      distinct differentiation at recurrences. CASE PRESENTATION: We report here a rare
      case of retroperitoneal schwannoma with multiple origins from retroperitoneum and
      pelvic wall. Pathological examination confirmed the case as a schwannoma with
      malignant transformation. Radical dissection of the tumors along with the
      sacrifice of adjacent sigmoid colon and left kidney failed to provide a cure for
      this patient. Due to tumor recurrence, a second and a third surgery of radical
      excision were performed 6 months and 17 months later after the first surgery,
      respectively. Histopathologic analysis identified that the recurrent tumors were
      different from the original schwannoma because of their smooth muscle-like
      differentiation. CONCLUSION: Malignant schwannomas are uncommon sarcomas with a
      high incidence of local recurrence. Distinct immunohistochemical staining results
      of the tumors at recurrence indicate their potential of smooth-muscle like
      differentiation. Radical excision of the tumors may provide benefit for their
      local recurrences.

PMID- 20696057
TI  - Performance of criteria for selecting evolutionary models in phylogenetics: a
      comprehensive study based on simulated datasets.
AB  - BACKGROUND: Explicit evolutionary models are required in maximum-likelihood and
      Bayesian inference, the two methods that are overwhelmingly used in phylogenetic
      studies of DNA sequence data. Appropriate selection of nucleotide substitution
      models is important because the use of incorrect models can mislead phylogenetic
      inference. To better understand the performance of different model-selection
      criteria, we used 33,600 simulated data sets to analyse the accuracy, precision,
      dissimilarity, and biases of the hierarchical likelihood-ratio test, Akaike
      information criterion, Bayesian information criterion, and decision theory.
      RESULTS: We demonstrate that the Bayesian information criterion and decision
      theory are the most appropriate model-selection criteria because of their high
      accuracy and precision. Our results also indicate that in some situations
      different models are selected by different criteria for the same dataset. Such
      dissimilarity was the highest between the hierarchical likelihood-ratio test and
      Akaike information criterion, and lowest between the Bayesian information
      criterion and decision theory. The hierarchical likelihood-ratio test performed
      poorly when the true model included a proportion of invariable sites, while the
      Bayesian information criterion and decision theory generally exhibited similar
      performance to each other. CONCLUSIONS: Our results indicate that the Bayesian
      information criterion and decision theory should be preferred for model
      selection. Together with model-adequacy tests, accurate model selection will
      serve to improve the reliability of phylogenetic inference and related analyses.

PMID- 20696060
TI  - Assessing weight perception accuracy to promote weight loss among U.S. female
      adolescents: a secondary analysis.
AB  - BACKGROUND: Overweight and obesity have become a global epidemic. The prevalence
      of overweight and obesity among U.S. adolescents has almost tripled in the last
      30 years. Results from recent systematic reviews demonstrate that no single,
      particular intervention or strategy successfully assists overweight or obese
      adolescents in losing weight. An understanding of factors that influence healthy
      weight-loss behaviors among overweight and obese female adolescents promotes
      effective, multi-component weight-loss interventions. There is limited evidence
      demonstrating associations between demographic variables, body-mass index, and
      weight perception among female adolescents trying to lose weight. There is also a
      lack of previous studies examining the association of the accuracy of female
      adolescents' weight perception with their efforts to lose weight. This study,
      therefore, examined the associations of body-mass index, weight perception, and
      weight-perception accuracy with trying to lose weight and engaging in exercise as
      a weight-loss method among a representative sample of U.S. female adolescents.
      METHODS: A nonexperimental, descriptive, comparative secondary analysis design
      was conducted using data from Wave II (1996) of the National Longitudinal Study
      of Adolescent Health (Add Health). Data representative of U.S. female adolescents
      (N = 2216) were analyzed using STATA statistical software. Descriptive statistics
      and survey weight logistic regression were performed to determine if demographic
      and independent (body-mass index, weight perception, and weight perception
      accuracy) variables were associated with trying to lose weight and engaging in
      exercise as a weight-loss method. RESULTS: Age, Black or African American race,
      body-mass index, weight perception, and weight perceptions accuracy were
      consistently associated with the likeliness of trying to lose weight among U.S.
      female adolescents. Age, body-mass index, weight perception, and weight
      perception accuracy were positively associated (p < 0.05) with trying to lose
      weight. Black/African American subjects were significantly less likely than their
      White counterparts to be trying to lose weight. There was no association between
      demographic or independent variables and engaging in exercise as a weight-loss
      method. CONCLUSIONS: Findings suggest that factors influencing weight-loss
      efforts, including age, race, body-mass index, weight perception, and weight
      perception accuracy, should be incorporated into existing or new multi-component
      weight-loss interventions for U.S. adolescent females in order to help reduce the
      national epidemic of overweight and obesity among U.S. female adolescents.

PMID- 20696059
TI  - Anti-tumor effects of retinoids combined with trastuzumab or tamoxifen in breast
      cancer cells: induction of apoptosis by retinoid/trastuzumab combinations.
AB  - INTRODUCTION: HER2 and estrogen receptor (ER) are important in breast cancer and
      are therapeutic targets of trastuzumab (Herceptin) and tamoxifen, respectively.
      Retinoids inhibit breast cancer growth, and modulate signaling by HER2 and ER. We
      hypothesized that treatment with retinoids and simultaneous targeting of HER2
      and/or ER may have enhanced anti-tumor effects. METHODS: The effects of retinoids
      combined with trastuzumab or tamoxifen were examined in two human breast cancer
      cell lines in culture, BT474 and SKBR3. Assays of proliferation, apoptosis,
      differentiation, cell cycle distribution, and receptor signaling were performed.
      RESULTS: In HER2-overexpressing/ER-positive BT474 cells, combining all-trans
      retinoic acid (atRA) with tamoxifen or trastuzumab synergistically inhibited cell
      growth, and altered cell differentiation and cell cycle. Only atRA/trastuzumab
      containing combinations induced apoptosis. BT474 and HER2-overexpressing/ER
      negative SKBR3 cells were treated with a panel of retinoids (atRA, 9-cis-retinoic
      acid, 13-cis-retinoic acid, or N-(4-hydroxyphenyl) retinamide (fenretinide) (4
      HPR)) combined with trastuzumab. In BT474 cells, none of the single agents except
      4-HPR induced apoptosis, but again combinations of each retinoid with trastuzumab
      did induce apoptosis. In contrast, the single retinoid agents did cause apoptosis
      in SKBR3 cells; this was only modestly enhanced by addition of trastuzumab. The
      retinoid drug combinations altered signaling by HER2 and ER. Retinoids were
      inactive in trastuzumab-resistant BT474 cells. CONCLUSIONS: Combining retinoids
      with trastuzumab maximally inhibits cell growth and induces apoptosis in
      trastuzumab-sensitive cells. Treatment with such combinations may have benefit
      for breast cancer patients.

PMID- 20696061
TI  - Rapid modification of the insect elicitor N-linolenoyl-glutamate via a
      lipoxygenase-mediated mechanism on Nicotiana attenuata leaves.
AB  - BACKGROUND: Some plants distinguish mechanical wounding from herbivore attack by
      recognizing specific constituents of larval oral secretions (OS) which are
      introduced into plant wounds during feeding. Fatty acid-amino acid conjugates
      (FACs) are major constituents of Manduca sexta OS and strong elicitors of
      herbivore-induced defense responses in Nicotiana attenuata plants. RESULTS: The
      metabolism of one of the major FACs in M. sexta OS, N-linolenoyl-glutamic acid
      (18:3-Glu), was analyzed on N. attenuata wounded leaf surfaces. Between 50 to 70%
      of the 18:3-Glu in the OS or of synthetic 18:3-Glu were metabolized within 30
      seconds of application to leaf wounds. This heat-labile process did not result in
      free alpha-linolenic acid (18:3) and glutamate but in the biogenesis of
      metabolites both more and less polar than 18:3-Glu. Identification of the major
      modified forms of this FAC showed that they corresponded to 13-hydroxy-18:3-Glu,
      13-hydroperoxy-18:3-Glu and 13-oxo-13:2-Glu. The formation of these metabolites
      occurred on the wounded leaf surface and it was dependent on lipoxygenase (LOX)
      activity; plants silenced in the expression of NaLOX2 and NaLOX3 genes showed
      more than 50% reduced rates of 18:3-Glu conversion and accumulated smaller
      amounts of the oxygenated derivatives compared to wild-type plants. Similar to
      18:3-Glu, 13-oxo-13:2-Glu activated the enhanced accumulation of jasmonic acid
      (JA) in N. attenuata leaves whereas 13-hydroxy-18:3-Glu did not. Moreover,
      compared to 18:3-Glu elicitation, 13-oxo-13:2-Glu induced the differential
      emission of two monoterpene volatiles (beta-pinene and an unidentified
      monoterpene) in irlox2 plants. CONCLUSIONS: The metabolism of one of the major
      elicitors of herbivore-specific responses in N. attenuata plants, 18:3-Glu,
      results in the formation of oxidized forms of this FAC by a LOX-dependent
      mechanism. One of these derivatives, 13-oxo-13:2-Glu, is an active elicitor of JA
      biosynthesis and differential monoterpene emission.

PMID- 20696062
TI  - Impact of RNA degradation on gene expression profiling.
AB  - BACKGROUND: Gene expression profiling is a highly sensitive technique which is
      used for profiling tumor samples for medical prognosis. RNA quality and
      degradation influence the analysis results of gene expression profiles. The
      impact of this influence on the profiles and its medical impact is not fully
      understood. As patient samples are very valuable for clinical studies, it is
      necessary to establish criteria for the RNA quality to be able to use these
      samples in later analysis. METHODS: To investigate the effects of RNA integrity
      on gene expression profiling, whole genome expression arrays were used. We used
      tumor biopsies from patients diagnosed with locally advanced rectal cancer. To
      simulate degradation, the isolated total RNA of all patients was subjected to
      heat-induced degradation in a time-dependent manner. Expression profiling was
      then performed and data were analyzed bioinformatically to assess the
      differences. RESULTS: The differences introduced by RNA degradation were largely
      outweighed by the biological differences between the patients. Only a relatively
      small number of probes (275 out of 41,000) show a significant effect due to
      degradation. The genes that show the strongest effect due to RNA degradation
      were, especially, those with short mRNAs and probe positions near the 5' end.
      CONCLUSIONS: Degraded RNA from tumor samples (RIN > 5) can still be used to
      perform gene expression analysis. A much higher biological variance between
      patients is observed compared to the effect that is imposed by degradation of
      RNA. Nevertheless there are genes, very short ones and those with the probe
      binding side close to the 5' end that should be excluded from gene expression
      analysis when working with degraded RNA. These results are limited to the Agilent
      44 k microarray platform and should be carefully interpreted when transferring to
      other settings.

PMID- 20696063
TI  - Bridging time scales in cellular decision making with a stochastic bistable
      switch.
AB  - BACKGROUND: Cellular transformations which involve a significant phenotypical
      change of the cell's state use bistable biochemical switches as underlying
      decision systems. Some of these transformations act over a very long time scale
      on the cell population level, up to the entire lifespan of the organism. RESULTS:
      In this work, we aim at linking cellular decisions taking place on a time scale
      of years to decades with the biochemical dynamics in signal transduction and gene
      regulation, occurring on a time scale of minutes to hours. We show that a
      stochastic bistable switch forms a viable biochemical mechanism to implement
      decision processes on long time scales. As a case study, the mechanism is applied
      to model the initiation of follicle growth in mammalian ovaries, where the
      physiological time scale of follicle pool depletion is on the order of the
      organism's lifespan. We construct a simple mathematical model for this process
      based on experimental evidence for the involved genetic mechanisms. CONCLUSIONS:
      Despite the underlying stochasticity, the proposed mechanism turns out to yield
      reliable behavior in large populations of cells subject to the considered
      decision process. Our model explains how the physiological time constant may
      emerge from the intrinsic stochasticity of the underlying gene regulatory
      network. Apart from ovarian follicles, the proposed mechanism may also be of
      relevance for other physiological systems where cells take binary decisions over
      a long time scale.

PMID- 20696064
TI  - Outcome measures of the 6 minute walk test: relationships with physiologic and
      computed tomography findings in patients with sarcoidosis.
AB  - BACKGROUND: We assessed the relationship between physiologic parameters, computed
      tomography patterns, 6 minute walk distance (6MWD) and the distance-saturation
      product [DSP; defined as the product of the 6MWD and the lowest oxygen saturation
      during the 6 minute walk test (6MWT)]. In addition, we investigated factors
      affecting 6MWD in patients with pulmonary sarcoidosis. METHODS: We performed a
      retrospective study of patient demographics, treatment, pulmonary function, 6MWT,
      echocardiography and computed tomography results. RESULTS: Fifty nine patients
      were included in this study. Their mean+standard deviation age was 47.5 years +
      12.5 years, and 42 (71.2%) were female. Mean pulmonary function parameters for
      forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1) and
      total lung capacity (TLC) results, as percentages of predicted values, were 77.6
      +/- 22.2, 77.1 +/- 22.8 and 78.7 +/- 16.1, respectively. Comparison of the DSP
      with distance walked revealed a significant correlation with factors underlying
      reduced 6MWD, including gender, pulmonary function indices, partial pressure of
      oxygen (PaO2), and Borg dyspnea score. Other factors were significantly
      associated with DSP but not distance; these included lung fibrosis (p = 0.02),
      pulmonary hypertension (p = 0.01) and systemic therapy (p = 0.04). Backward
      elimination stepwise multiple regression analysis revealed that gender, and FEV1
      were independent predictors of 6MWD, but FEV1 was more strongly related when DSP
      applied [DSP, R2 = 0.53, p = 0.02; distance, R2 = 0.45, p < 0.0001]. CONCLUSION:
      Our findings reveal that, compared to 6MWD alone, the DSP is correlated with a
      greater number of factors associated with reduced 6MWT performance. Therefore,
      the DSP may be a useful indicator of functional status in patients with
      sarcoidosis. Additional large-scale studies are warranted to validate our
      findings.

PMID- 20696065
TI  - Nosocomial Rotavirus Gastroenteritis in pediatric patients: a multi-center
      prospective cohort study.
AB  - BACKGROUND: Few data are available on the incidence of nosocomial Rotavirus
      infections (NRVI) in pediatric hospitals and on their economic impact. The goals
      of this study were: to evaluate the incidence of NRVI in various Italian
      pediatric wards during the course of two peak RV seasons; to investigate possible
      risk factors for NRVI; to estimate the costs caused by NRVI. METHODS: prospective
      cohort study. POPULATION: All the children under 30 months of age who were
      admitted without any symptom or diagnosis of gastroenteritis in the pediatric
      hospitals of Florence, Naples, Brescia and Ancona, Italy, during the winter
      spring periods 2006-2007 and 2007-2008. Serial RV rapid tests and clinical
      monitoring were carried out on the cohort. Telephone interviews were performed
      from 3 to 5 days after discharge. RESULTS: 520 out of 608 children completed the
      study (85.6%). The overall incidence of NRVI was 5.3% (CI95% 3.6-7.5), (7.9 per
      1,000 days of hospital stay, CI 95% 5.3-11.3). The average duration of hospital
      stay was significantly longer for children who had NRVI (8.1 days, SD 5.4) than
      for non-infected children (6.4 days, SD 5.8, difference 1.7 days, p = 0.004). The
      risk of contracting NRVI increased significantly if the child stayed in hospital
      more than 5 days, RR = 2.8 (CI95% 1.3-6), p = 0.006. In Italy the costs caused by
      NRVI can be estimated at 8,019,155.44 Euro per year. 2.7% of the children
      hospitalized with no gastroenteritis symptoms tested positive for RV.
      CONCLUSIONS: Our study showed a relevant incidence of NRVI, which can increase
      the length of the children's stay in hospital. Limiting the number of nosocomial
      RV infections is important to improve patients' safety as well as to avoid
      additional health costs.

PMID- 20696066
TI  - Development of efficient plant regeneration and transformation system for
      impatiens using Agrobacterium tumefaciens and multiple bud cultures as explants.
AB  - BACKGROUND: Impatiens (Impatiens walleriana) is a top selling floriculture crop.
      The potential for genetic transformation of Impatiens to introduce novel flower
      colors or virus resistance has been limited by its general recalcitrance to
      tissue culture and transformation manipulations. We have established a
      regeneration and transformation system for Impatiens that provides new
      alternatives to genetic improvement of this crop. RESULTS: In a first step
      towards the development of transgenic INSV-resistant Impatiens, we developed an
      efficient plant regeneration system using hypocotyl segments containing
      cotyledonary nodes as explants. With this regeneration system, 80% of explants
      produced an average of 32.3 elongated shoots per initial explant plated, with up
      to 167 elongated shoots produced per explant. Rooting efficiency was high, and
      100% of shoots produced roots within 12 days under optimal conditions, allowing
      plant regeneration within approximately 8 weeks. Using this regeneration system,
      we developed an efficient Agrobacterium-mediated Impatiens transformation method
      using in vitro multiple bud cultures as explants and a binary plasmid (pHB2892)
      bearing gfp and nptII genes. Transgenic Impatiens plants, with a frequency up to
      58.9%, were obtained within 12 to 16 weeks from inoculation to transfer of
      transgenic plants to soil. Transgenic plants were confirmed by Southern blot,
      phenotypic assays and T1 segregation analysis. Transgene expression was observed
      in leaves, stems, roots, flowers, and fruit. The transgenic plants were fertile
      and phenotypically normal. CONCLUSION: We report the development of a simple and
      efficient Agrobacterium-mediated transformation system for Impatiens. To the best
      of our knowledge, there have been no reports of Agrobacterium-mediated
      transformation of Impatiens with experimental evidence of stable integration of T
      DNA and of Agrobacterium-mediated transformation method for plants using in vitro
      maintained multiple bud cultures as explants. This transformation system has the
      advantages of 1) efficient, simple and rapid regeneration and transformation
      (with no need for sterilization or a greenhouse to grow stock plants), 2)
      flexibility (available all the time) for in vitro manipulation, 3) uniform and
      desirable green tissue explants for both nuclear and plastid transformation using
      Agrobacterium-mediated and biolistics methods, 4) no somaclonal variation and 5)
      resolution of necrosis of Agrobacterium-inoculated tissues.

PMID- 20696067
TI  - Moisture-induced solid state instabilities in alpha-chymotrypsin and their
      reduction through chemical glycosylation.
AB  - BACKGROUND: Protein instability remains the main factor limiting the development
      of protein therapeutics. The fragile nature (structurally and chemically) of
      proteins makes them susceptible to detrimental events during processing, storage,
      and delivery. To overcome this, proteins are often formulated in the solid-state
      which combines superior stability properties with reduced operational costs.
      Nevertheless, solid protein pharmaceuticals can also suffer from instability
      problems due to moisture sorption. Chemical protein glycosylation has evolved
      into an important tool to overcome several instability issues associated with
      proteins. Herein, we employed chemical glycosylation to stabilize a solid-state
      protein formulation against moisture-induced deterioration in the lyophilized
      state. RESULTS: First, we investigated the consequences of moisture sorption on
      the stability and structural conformation of the model enzyme alpha-chymotrypsin
      (alpha-CT) under controlled humidity conditions. Results showed that alpha-CT
      aggregates and inactivates as a function of increased relative humidity (RH).
      Furthermore, alpha-CT loses its native secondary and tertiary structure rapidly
      at increasing RH. In addition, H/D exchange studies revealed that alpha-CT
      structural dynamics increased at increasing RH. The magnitude of the structural
      changes in tendency parallels the solid-state instability data (i.e., formation
      of buffer-insoluble aggregates, inactivation, and loss of native conformation
      upon reconstitution). To determine if these moisture-induced instability issues
      could be ameliorated by chemical glycosylation we proceeded to modify our model
      protein with chemically activated glycans of differing lengths (lactose and
      dextran (10 kDa)). The various glycoconjugates showed a marked decrease in
      aggregation and an increase in residual activity after incubation. These
      stabilization effects were found to be independent of the glycan size.
      CONCLUSION: Water sorption leads to aggregation, inactivation, and structural
      changes of alpha-CT as has been similarly shown to occur for many other proteins.
      These instabilities correlate with an increase in protein structural dynamics as
      a result of moisture exposure. In this work, we present a novel methodology to
      stabilize proteins against structural perturbations in the solid-state since
      chemical glycosylation was effective in decreasing and/or preventing the
      traditionally observed moisture-induced aggregation and inactivation. It is
      suggested that the stabilization provided by these chemically attached glycans
      comes from the steric hindrance that the sugars conveys on the protein surface
      therefore preventing the interaction of the protein internal electrostatics with
      that of the water molecules and thus reducing the protein structural dynamics
      upon moisture exposure.

PMID- 20696068
TI  - Untangling spider silk evolution with spidroin terminal domains.
AB  - BACKGROUND: Spidroins are a unique family of large, structural proteins that make
      up the bulk of spider silk fibers. Due to the highly variable nature of their
      repetitive sequences, spidroin evolutionary relationships have principally been
      determined from their non-repetitive carboxy (C)-terminal domains, though they
      offer limited character data. The few known spidroin amino (N)-terminal domains
      have been difficult to obtain, but potentially contain critical phylogenetic
      information for reconstructing the diversification of spider silks. Here we used
      silk gland expression data (ESTs) from highly divergent species to evaluate the
      functional significance and phylogenetic utility of spidroin N-terminal domains.
      RESULTS: We report 11 additional spidroin N-termini found by sequencing
      approximately 1,900 silk gland cDNAs from nine spider species that shared a
      common ancestor > 240 million years ago. In contrast to their hyper-variable
      repetitive regions, spidroin N-terminal domains have retained striking
      similarities in sequence identity, predicted secondary structure, and
      hydrophobicity. Through separate and combined phylogenetic analyses of N-terminal
      domains and their corresponding C-termini, we find that combined analysis
      produces the most resolved trees and that N-termini contribute more support and
      less conflict than the C-termini. These analyses show that paralogs largely group
      by silk gland type, except for the major ampullate spidroins. Moreover, spidroin
      structural motifs associated with superior tensile strength arose early in the
      history of this gene family, whereas a motif conferring greater extensibility
      convergently evolved in two distantly related paralogs. CONCLUSIONS: A non
      repetitive N-terminal domain appears to be a universal attribute of spidroin
      proteins, likely retained from the origin of spider silk production. Since this
      time, spidroin N-termini have maintained several features, consistent with this
      domain playing a key role in silk assembly. Phylogenetic analyses of the
      conserved N- and C-terminal domains illustrate dramatic radiation of the spidroin
      gene family, involving extensive duplications, shifts in expression patterns and
      extreme diversification of repetitive structural sequences that endow spider
      silks with an unparalleled range of mechanical properties.

PMID- 20696069
TI  - Airborne particulate matter and mitochondrial damage: a cross-sectional study.
AB  - Oxidative stress generation is a primary mechanism mediating the effects of
      Particulate Matter (PM) on human health. Although mitochondria are both the major
      intracellular source and target of oxidative stress, the effect of PM on
      mitochondria has never been evaluated in exposed individuals. METHODS: In 63 male
      healthy steel workers from Brescia, Italy, studied between April and May 2006, we
      evaluated whether exposure to PM was associated with increased mitochondrial DNA
      copy number (MtDNAcn), an established marker of mitochondria damage and
      malfunctioning. Relative MtDNAcn (RMtDNAcn) was determined by real-time PCR in
      blood DNA obtained on the 1st (time 1) and 4th day (time 2) of the same work
      week. Individual exposures to PM10, PM1, coarse particles (PM10-PM1) and airborne
      metal components of PM10 (chromium, lead, arsenic, nickel, manganese) were
      estimated based on measurements in the 11 work areas and time spent by the study
      subjects in each area. RESULTS: RMtDNAcn was higher on the 4th day (mean = 1.31;
      95%CI = 1.22 to 1.40) than on the 1st day of the work week (mean = 1.09; 95%CI =
      1.00 to 1.17). PM exposure was positively associated with RMtDNAcn on either the
      4th (PM10: beta = 0.06, 95%CI = -0.06 to 0.17; PM1: beta = 0.08, 95%CI = -0.08 to
      0.23; coarse: beta = 0.06, 95%CI = -0.06 to 0.17) or the 1st day (PM10: beta =
      0.18, 95%CI = 0.09 to 0.26; PM1: beta = 0.23, 95%CI = 0.11 to 0.35; coarse: beta
      = 0.17, 95%CI = 0.09 to 0.26). Metal concentrations were not associated with
      RMtDNAcn. CONCLUSIONS: PM exposure is associated with damaged mitochondria, as
      reflected in increased MtDNAcn. Damaged mitochondria may intensify oxidative
      stress production and effects.

PMID- 20696070
TI  - 'BeSAFE', effect-evaluation of internet-based, tailored safety information
      combined with personal counselling on parents' child safety behaviours: study
      design of a randomized controlled trial.
AB  - BACKGROUND: Injuries in or around the home are the most important cause of death
      among children aged 0-4 years old. It is also a major source of morbidity and
      loss of quality of life. In order to reduce the number of injuries, the Consumer
      Safety Institute introduced the use of Safety Information Leaflets in the
      Netherlands to provide safety education to parents of children aged 0-4 years.
      Despite current safety education, necessary safety behaviours are still not taken
      by a large number of parents, causing unnecessary risk of injury among young
      children. In an earlier study an E-health module with internet-based, tailored
      safety information was developed and applied. It concerns an advice for parents
      on safety behaviours in their homes regarding their child. The aim of this study
      is to evaluate the effect of this safety information combined with personal
      counselling on parents' child safety behaviours. METHODS/DESIGN: Parents who are
      eligible for the regular well-child visit with their child at child age 5-8
      months are invited to participate in this study. Participating parents are
      randomized into one of two groups: 1) internet-based, tailored safety information
      combined with personal counselling (intervention group), or 2) personal
      counselling using the Safety Information Leaflets of the Consumer Safety
      Institute in the Netherlands for children aged 12 to 24 months (control group).
      All parents receive safety information on safety topics regarding the prevention
      of falling, poisoning, drowning and burning. Parents of the intervention group
      will access the internet-based, tailored safety information module when their
      child is approximately 10 months old. After completion of the assessment
      questions, the program compiles a tailored safety advice. The parents are asked
      to devise and inscribe a personal implementation intention. During the next well
      child visit, the Child Health Clinic professional will discuss this tailored
      safety information and the implementation intention with the parents. The control
      group will receive usual care, i.e. the provision of Safety Information Leaflets
      during their well-child visit at the child's age of 11 months. DISCUSSION: It is
      hypothesized that the intervention, internet-based, tailored safety information
      combined with personal counselling results in more parents' child safety
      behaviours. TRIAL REGISTRATION: Current Controlled Trials NTR1836.

PMID- 20696071
TI  - Bone events and evolution of biologic markers in Gaucher disease before and
      during treatment.
AB  - INTRODUCTION: Known biomarkers of Gaucher-disease activity are platelets,
      chitotriosidase, angiotensin-converting enzyme (ACE), tartrate-resistant acid
      phosphatase (TRAP) and ferritin. The aim of this study was to retrospectively
      evaluate the frequency of bone events (BE) and biomarker changes during two
      periods: diagnosis to first enzyme-replacement therapy (ERT) and the latter to
      the closing date. METHODS: BE of 62 treated patients, among the 73-patient cohort
      followed at Beaujon Hospital, Clichy, France, were described with Kaplan-Meier
      curves, and linear-mixed models were used to analyze their biomarker changes and
      the influence of several covariates (splenectomy, diagnosis year, genotype, age
      at diagnosis and sex). RESULTS: BE occurred before (54 events in 21 patients),
      but also during, ERT (12 events in 10 patients), with respective frequencies (95%
      confidence interval) at 10 years of 22.4% (13.3 to 36.3) and 20.0% (10.2 to
      36.9). Biomarker slope changes before and during ERT differed significantly for
      platelets (+190/mm3/year and 7,035/mm3/year, respectively; P < 0.0001) and
      ferritin (+4% and -14%; P < 0.0001). High ferritin levels and low platelet counts
      at ERT onset were significantly associated with BE during ERT (P = 0.019 and
      0.039, respectively). Covariates significantly influenced biomarker changes
      (baseline and/or slope): splenectomy affected platelets (baseline and changes),
      TRAP changes and chitotriosidase changes; diagnosis date influenced ACE and TRAP
      baseline values; and genotype influenced chitotriosidase baseline and changes.
      CONCLUSIONS: Platelet counts and ferritin levels and their slope changes at ERT
      onset seem to predict BE during treatment. Biomarker baseline values and changes
      are dependent on several covariables.

PMID- 20696072
TI  - Association between weight perception and socioeconomic status among adults in
      the Seychelles.
AB  - BACKGROUND: Few studies have examined the association between weight perception
      and socioeconomic status (SES) in sub-Saharan Africa, and none made this
      association based on education, occupation and income simultaneously. METHODS:
      Based on a population-based survey (n = 1255) in the Seychelles, weight and
      height were measured and self-perception of one's own body weight, education,
      occupation, and income were assessed by a questionnaire. Individuals were
      considered to have appropriate weight perception when their self-perceived weight
      matched their actual body weight. RESULTS: The prevalence of overweight and
      obesity was 35% and 28%, respectively. Multivariate analysis among
      overweight/obese persons showed that appropriate weight perception was directly
      associated with actual weight, education, occupation and income, and that it was
      more frequent among women than among men. In a model using all three SES
      indicators together, only education (OR = 2.5; 95% CI: 1.3-4.8) and occupation
      (OR = 2.3; 95% CI: 1.2-4.5) were independently associated with appropriate
      perception of being overweight. The OR reached 6.9 [95% CI: 3.4-14.1] when
      comparing the highest vs. lowest categories of SES based on a score including all
      SES indicators and 6.1 [95% CI: 3.0-12.1] for a score based on education and
      occupation. CONCLUSIONS: Appropriately perceiving one's weight as too high was
      associated with different SES indicators, female sex and being actually
      overweight. These findings suggest means and targets for clinical and population
      based interventions for weight control. Further studies should examine whether
      these differences in weight perception underlie differences in cognitive skills,
      healthy weight norms, or body size ideals.

PMID- 20696073
TI  - A systematic review of economic analyses of telehealth services using real time
      video communication.
AB  - BACKGROUND: Telehealth is the delivery of health care at a distance, using
      information and communication technology. The major rationales for its
      introduction have been to decrease costs, improve efficiency and increase access
      in health care delivery. This systematic review assesses the economic value of
      one type of telehealth delivery--synchronous or real time video communication-
      rather than examining a heterogeneous range of delivery modes as has been the
      case with previous reviews in this area. METHODS: A systematic search was
      undertaken for economic analyses of the clinical use of telehealth, ending in
      June 2009. Studies with patient outcome data and a non-telehealth comparator were
      included. Cost analyses, non-comparative studies and those where patient
      satisfaction was the only health outcome were excluded. RESULTS: 36 articles met
      the inclusion criteria. 22(61%) of the studies found telehealth to be less costly
      than the non-telehealth alternative, 11(31%) found greater costs and 3 (9%) gave
      the same or mixed results. 23 of the studies took the perspective of the health
      services, 12 were societal, and one was from the patient perspective. In three
      studies of telehealth to rural areas, the health services paid more for
      telehealth, but due to savings in patient travel, the societal perspective
      demonstrated cost savings. In regard to health outcomes, 12 (33%) of studies
      found improved health outcomes, 21 (58%) found outcomes were not significantly
      different, 2(6%) found that telehealth was less effective, and 1 (3%) found
      outcomes differed according to patient group. The organisational model of care
      was more important in determining the value of the service than the clinical
      discipline, the type of technology, or the date of the study. CONCLUSION:
      Delivery of health services by real time video communication was cost-effective
      for home care and access to on-call hospital specialists, showed mixed results
      for rural service delivery, and was not cost-effective for local delivery of
      services between hospitals and primary care.

PMID- 20696074
TI  - Comparison of laser Doppler imaging, fingertip lacticemy test, and nailfold
      capillaroscopy for assessment of digital microcirculation in systemic sclerosis.
AB  - INTRODUCTION: Laser Doppler imaging (LDI) is a relatively new method for
      assessing the functional aspect of superficial skin blood flow in systemic
      sclerosis (SSc) and Raynaud's phenomenon. The present study investigated the
      dynamic behavior of digital skin microvascular blood flow before and after cold
      stimulus (CS) in SSc patients and in healthy controls by means of a comprehensive
      approach of the functional (LDI), morphological (nailfold capillaroscopy (NFC)),
      and biochemical (fingertip lacticemy (FTL)) microcirculation components. METHODS:
      Forty-four SSc patients and 40 healthy controls were included. After
      acclimatization, all subjects underwent NFC followed by LDI and FTL measurement.
      NFC was performed with a stereomicroscope under 10* to 20* magnification in the
      10 digits of the hands. Skin blood flow of the dorsum of four fingertips
      (excluding the thumb) of the left hand was measured using LDI at baseline and for
      30 minutes after CS. The mean finger blood flow (FBF) of the four fingertips was
      expressed as arbitrary perfusion units. FTL was determined on the fourth left
      finger before (pre-CS-FTL) and 10 minutes after CS. RESULTS: LDI showed
      significantly lower mean baseline FBF in SSc patients as compared with controls
      (296.9 +/- 208.8 vs. 503.6 +/- 146.4 perfusion units; P < 0.001) and also at all
      time points after CS (P < 0.001). There was a significant decrease in mean FBF
      after CS as compared with baseline in SSc patients and in controls, followed by
      recovery of the blood flow 27 minutes after CS in healthy controls, but not in
      SSc patients. FBF tended to be lower in patients with digital scars and previous
      ulceration/amputation (P = 0.06). There was no correlation between mean baseline
      FBF and NFC parameters. Interestingly, there was a negative correlation between
      FTL and FBF measured by LDI in basal conditions and 10 minutes after CS in SSc
      patients. CONCLUSIONS: LDI showed lower digital blood flow in SSc patients when
      compared with healthy controls and correlated well with FTL both at baseline and
      after CS, allowing objective measurement of blood perfusion in SSc patients. The
      lack of correlation between functional and morphological microvascular
      abnormalities, measured by LDI and NFC, suggests they are complementary tools for
      evaluation of independent microangiopathy aspects in SSc patients.

PMID- 20696075
TI  - Association of the apolipoprotein A5 gene -1131 T>C polymorphism with fasting
      blood lipids: a meta-analysis in 37859 subjects.
AB  - BACKGROUND: Studies examining the association of apolipoprotein A5 (APOA5) gene 
      1131 T>C polymorphism with blood lipids produced inconsistent results. In this
      meta-analysis encompassing all the relevant studies, we aimed to investigate the
      association of the -1131 T>C polymorphism with fasting blood lipids. METHODS: We
      limited our analysis to the following four blood lipid variables: total
      cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL
      C), and high-density lipoprotein cholesterol (HDL-C). Subjects were confined to
      adults who were at least 18 years old. A dominant model was used for this meta
      analysis. 37 studies with 37859 subjects were included in this meta-analysis.
      RESULTS: The results showed that the carriers of -1131C allele have higher blood
      TC and TG than the non-carriers: standardized mean difference (SMD) = 0.08, 95%
      confidence interval (CI, 0.05, 0.11), P < 0.00001, P(heterogeneity) = 0.42, and
      SMD = 0.31, 95% CI (0.27, 0.34), P < 0.00001, P(heterogeneity) = 0.0003,
      respectively. Significant association between the -1131 T>C polymorphism and
      lower blood HDL-C was also detected under the dominant model: SMD = -0.17, 95% CI
      (-0.21, -0.14), P < 0.00001, P(heterogeneity) = 0.003. CONCLUSIONS: Our meta
      analysis supports the strong association of the APOA5 -1131 T>C polymorphism with
      higher levels of TC and TG, and lower levels of HDL-C.

PMID- 20696076
TI  - Production of erythriod cells from human embryonic stem cells by fetal liver cell
      extract treatment.
AB  - BACKGROUND: We recently developed a new method to induce human stem cells (hESCs)
      differentiation into hematopoietic progenitors by cell extract treatment. Here,
      we report an efficient strategy to generate erythroid progenitors from hESCs
      using cell extract from human fetal liver tissue (hFLT) with cytokines. Human
      embryoid bodies (hEBs) obtained of human H1 hESCs were treated with cell extract
      from hFLT and co-cultured with human fetal liver stromal cells (hFLSCs) feeder to
      induce hematopoietic cells. After the 11 days of treatment, hEBs were isolated
      and transplanted into liquid medium with hematopoietic cytokines for erythroid
      differentiation. Characteristics of the erythroid cells were analyzed by flow
      cytometry, Wright-Giemsa staining, real-time RT-PCR and related functional
      assays. RESULTS: The erythroid cells produced from hEBs could differentiate into
      enucleated cells and expressed globins in a time-dependent manner. They expressed
      not only embryonic globins but also the adult-globin with the maturation of the
      erythroid cells. In addition, our data showed that the hEBs-derived erythroid
      cells were able to act as oxygen carriers, indicating that hESCs could generate
      functional mature erythroid cells. CONCLUSION: Cell extract exposure with the
      addition of cytokines resulted in robust erythroid -like differentiation of hEBs
      and these hEBs-derived erythroid cells possessed functions similar to mature red
      blood cells.

PMID- 20696077
TI  - Nuclear beta-catenin and CD44 upregulation characterize invasive cell populations
      in non-aggressive MCF-7 breast cancer cells.
AB  - BACKGROUND: In breast cancer cells, the metastatic cell state is strongly
      correlated to epithelial-to-mesenchymal transition (EMT) and the CD44+/CD24- stem
      cell phenotype. However, the MCF-7 cell line, which has a luminal epithelial-like
      phenotype and lacks a CD44+/CD24- subpopulation, has rare cell populations with
      higher Matrigel invasive ability. Thus, what are the potentially important
      differences between invasive and non-invasive breast cancer cells, and are the
      differences related to EMT or CD44/CD24 expression? METHODS: Throughout the
      sequential selection process using Matrigel, we obtained MCF-7-14 cells of
      opposite migratory and invasive capabilities from MCF-7 cells. Comparative
      analysis of epithelial and mesenchymal marker expression was performed between
      parental MCF-7, selected MCF-7-14, and aggressive mesenchymal MDA-MB-231 cells.
      Furthermore, using microarray expression profiles of these cells, we selected
      differentially expressed genes for their invasive potential, and performed
      pathway and network analysis to identify a set of interesting genes, which were
      evaluated by RT-PCR, flow cytometry or function-blocking antibody treatment.
      RESULTS: MCF-7-14 cells had enhanced migratory and invasive ability compared with
      MCF-7 cells. Although MCF-7-14 cells, similar to MCF-7 cells, expressed E
      cadherin but neither vimentin nor fibronectin, beta-catenin was expressed not
      only on the cell membrane but also in the nucleus. Furthermore, using gene
      expression profiles of MCF-7, MCF-7-14 and MDA-MB-231 cells, we demonstrated that
      MCF-7-14 cells have alterations in signaling pathways regulating cell migration
      and identified a set of genes (PIK3R1, SOCS2, BMP7, CD44 and CD24).
      Interestingly, MCF-7-14 and its invasive clone CL6 cells displayed increased CD44
      expression and downregulated CD24 expression compared with MCF-7 cells. Anti-CD44
      antibody treatment significantly decreased cell migration and invasion in both
      MCF-7-14 and MCF-7-14 CL6 cells as well as MDA-MB-231 cells. CONCLUSIONS: MCF-7
      14 cells are a novel model for breast cancer metastasis without requiring
      constitutive EMT and are categorized as a "metastable phenotype", which can be
      distinguished from both epithelial and mesenchymal cells. The alterations and
      characteristics of MCF-7-14 cells, especially nuclear beta-catenin and CD44
      upregulation, may characterize invasive cell populations in breast cancer.

PMID- 20696078
TI  - Test-retest reliability of selected items of Health Behaviour in School-aged
      Children (HBSC) survey questionnaire in Beijing, China.
AB  - BACKGROUND: Children's health and health behaviour are essential for their
      development and it is important to obtain abundant and accurate information to
      understand young people's health and health behaviour. The Health Behaviour in
      School-aged Children (HBSC) study is among the first large-scale international
      surveys on adolescent health through self-report questionnaires. So far, more
      than 40 countries in Europe and North America have been involved in the HBSC
      study. The purpose of this study is to assess the test-retest reliability of
      selected items in the Chinese version of the HBSC survey questionnaire in a
      sample of adolescents in Beijing, China. METHODS: A sample of 95 male and female
      students aged 11 or 15 years old participated in a test and retest with a three
      weeks interval. Student Identity numbers of respondents were utilized to permit
      matching of test-retest questionnaires. 23 items concerning physical activity,
      sedentary behaviour, sleep and substance use were evaluated by using the
      percentage of response shifts and the single measure Intraclass Correlation
      Coefficients (ICC) with 95% confidence interval (CI) for all respondents and
      stratified by gender and age. Items on substance use were only evaluated for
      school children aged 15 years old. RESULTS: The percentage of no response shift
      between test and retest varied from 32% for the item on computer use at weekends
      to 92% for the three items on smoking. Of all the 23 items evaluated, 6 items
      (26%) showed a moderate reliability, 12 items (52%) displayed a substantial
      reliability and 4 items (17%) indicated almost perfect reliability. No gender and
      age group difference of the test-retest reliability was found except for a few
      items on sedentary behaviour. CONCLUSIONS: The overall findings of this study
      suggest that most selected indicators in the HBSC survey questionnaire have
      satisfactory test-retest reliability for the students in Beijing. Further test
      retest studies in a large and diverse sample, as well as validity studies, should
      be considered for the future Chinese HBSC study.

PMID- 20696079
TI  - RNA Interference inhibits hepatitis B virus of different genotypes in vitro and
      in vivo.
AB  - BACKGROUND: Hepatitis B virus (HBV) infection increases the risk of liver disease
      and hepatocellular carcinoma. Small interfering RNA (siRNA) can be a potential
      new tool for HBV therapy. Given the high heterogeneity of HBV strains and the
      sensitivity towards sequences changes of siRNA, finding a potent siRNA inhibitor
      against the conservative site on the HBV genome is essential to ensure a
      therapeutic application. RESULTS: Forty short hairpin RNA (shRNA) expression
      plasmids were constructed to target conserved regions among nine HBV genotypes.
      HBV 1.3-fold genome plasmids carrying various genotypes were co-transfected with
      shRNA plasmids into either Huh7 cells or mice. The levels of various viral
      markers were examined to assess the anti-HBV efficacy of siRNA. Four (B245, B376,
      B1581 and B1789) were found with the ability to potently inhibit HBV RNA, DNA,
      surface antigen (HBsAg), e antigen (HBeAg) and core antigen (HBcAg) expression in
      HBV genotypes A, B, C, D and I (a newly identified genotype) in Huh7 cells and in
      mice. No unusual cytotoxicity or off-target effects were noted. CONCLUSIONS: Such
      siRNA suggests an alternate way of inhibiting various HBV genotypes in vitro and
      in vivo, promising advances in the treatment of HBV.

PMID- 20696080
TI  - Multi-agent modeling of the South Korean avian influenza epidemic.
AB  - BACKGROUND: Several highly pathogenic avian influenza (AI) outbreaks have been
      reported over the past decade. South Korea recently faced AI outbreaks whose
      economic impact was estimated to be 6.3 billion dollars, equivalent to nearly 50%
      of the profit generated by the poultry-related industries in 2008. In addition,
      AI is threatening to cause a human pandemic of potentially devastating
      proportions. Several studies show that a stochastic simulation model can be used
      to plan an efficient containment strategy on an emerging influenza. Efficient
      control of AI outbreaks based on such simulation studies could be an important
      strategy in minimizing its adverse economic and public health impacts. METHODS:
      We constructed a spatio-temporal multi-agent model of chickens and ducks in
      poultry farms in South Korea. The spatial domain, comprised of 76 (37.5 km x 37.5
      km) unit squares, approximated the size and scale of South Korea. In this spatial
      domain, we introduced 3,039 poultry flocks (corresponding to 2,231 flocks of
      chickens and 808 flocks of ducks) whose spatial distribution was proportional to
      the number of birds in each province. The model parameterizes the properties and
      dynamic behaviors of birds in poultry farms and quarantine plans and included
      infection probability, incubation period, interactions among birds, and
      quarantine region. RESULTS: We conducted sensitivity analysis for the different
      parameters in the model. Our study shows that the quarantine plan with well
      chosen values of parameters is critical for minimize loss of poultry flocks in an
      AI outbreak. Specifically, the aggressive culling plan of infected poultry farms
      over 18.75 km radius range is unlikely to be effective, resulting in higher
      fractions of unnecessarily culled poultry flocks and the weak culling plan is
      also unlikely to be effective, resulting in higher fractions of infected poultry
      flocks. CONCLUSIONS: Our results show that a prepared response with targeted
      quarantine protocols would have a high probability of containing the disease. The
      containment plan with an aggressive culling plan is not necessarily efficient,
      causing a higher fraction of unnecessarily culled poultry farms. Instead, it is
      necessary to balance culling with other important factors involved in AI
      spreading. Better estimations for the containment of AI spreading with this model
      offer the potential to reduce the loss of poultry and minimize economic impact on
      the poultry industry.

PMID- 20696081
TI  - TLR9 expression in glioma tissues correlated to glioma progression and the
      prognosis of GBM patients.
AB  - BACKGROUND: Our study aims to evaluate the expression of TLR9 in glioma tissues,
      examine the association between TLR9 expression, clinicopathological variables,
      and glioma patient outcome, we further characterized the direct effects of TLR9
      agonist CpG ODN upon the proliferation and invasion of glioma cells in vitro.
      METHODS: RT-PCR and immunofluorescence were used to determine the expression of
      TLR9 in glioma cell lines and clinical glioma samples. Tissue microarry and
      immunohistochemistry were applied to evaluated TLR9 expression in 292 newly
      diagnosed glioma and 13 non-neoplastic brain tissues. We further investigated the
      effect of CpG ODN on the proliferation and invasion of glioma cells in vitro with
      MTT assays and matrigel transwell assay respectively. RESULTS: RT-PCR showed that
      TLR9 expressed in all the glioma samples and glioma cell lines we examined. The
      tissue array analysis indicated that TLR9 expression is correlated with
      malignancy of glioma (p < 0.01). Multivariate Cox regression analysis revealed
      that TLR9 expression is an independent prognostic factor for PFS of GBM patients
      (P = 0.026). TLR9 agonist CpG ODN has no significant effect on glioma
      proliferation, but matrigel transwell analysis showed that TLR9 agonist CpG ODN
      can significantly enhance glioma invasion in vitro. CONCLUSIONS: Our data
      indicated that TLR9 expression increases according to the histopathological grade
      of glioma, and the TLR9 expression level is related to the PFS of GBM patients.
      In addition, our findings warrant caution in the directly injection of TLR9
      agonist CpG ODN into glioma tissues for the glioma immunotherapy.

PMID- 20696082
TI  - Identification of a novel homozygous nonsense mutation in EYS in a Chinese family
      with autosomal recessive retinitis pigmentosa.
AB  - BACKGROUND: Retinitis pigmentosa is the most important hereditary retinal
      degenerative disease, which has a high degree of clinical and genetic
      heterogeneity. More than half of all cases of retinitis pigmentosa are autosomal
      recessive (arRP), but the gene(s) causing arRP in most families has yet to be
      identified. The purpose of this study is to identify the genetic basis of severe
      arRP in a consanguineous Chinese family. METHODS: Linkage and haplotype analyses
      were used to define the chromosomal location of the pathogenic gene in the
      Chinese arRP family. Direct DNA sequence analysis of the entire coding region and
      exon-intron boundaries of EYS was used to determine the disease-causing mutation,
      and to demonstrate that the mutation co-segregates with the disease in the
      family. RESULTS: A single nucleotide substitution of G to T at nucleotide 5506 of
      EYS was identified in the Chinese arRP family. This change caused a substitution
      of a glutamic acid residue at codon 1,836 by a stop codon TAA (p.E1836X), and
      resulted in a premature truncated EYS protein with 1,835 amino acids. Three
      affected siblings in the family were homozygous for the p.E1836X mutation, while
      the other unaffected family members carried one mutant allele and one normal EYS
      allele. The nonsense mutation p.E1836X was not detected in 200 unrelated normal
      controls. CONCLUSIONS: The EYS gene is a recently identified disease-causing gene
      for retinitis pigmentosa, and encodes the orthologue of Drosophila spacemaker. To
      date, there are only eight mutations in EYS that have been identified to cause
      arRP. Here we report one novel homozygous nonsense mutation of EYS in a
      consanguineous Chinese arRP family. Our study represents the first independent
      confirmation that mutations in EYS cause arRP. Additionally, this is the first
      EYS mutation identified in the Chinese population.

PMID- 20696083
TI  - Efficacy and safety of an antiviral Iota-Carrageenan nasal spray: a randomized,
      double-blind, placebo-controlled exploratory study in volunteers with early
      symptoms of the common cold.
AB  - BACKGROUND: The common cold, the most prevalent contagious viral disease in
      humans still lacks a safe and effective antiviral treatment. Iota-Carrageenan is
      broadly active against respiratory viruses in-vitro and has an excellent safety
      profile. This study investigated the efficacy and safety of an Iota-Carrageenan
      nasal spray in patients with common cold symptoms. METHODS: In a randomized,
      double-blind, placebo-controlled exploratory trial, 35 human subjects suffering
      from early symptoms of common cold received Iota-Carrageenan (0.12%) in a saline
      solution three times daily for 4 days, compared to placebo. RESULTS:
      Administration of Iota-Carrageenan nasal spray reduced the symptoms of common
      cold (p = 0.046) and the viral load in nasal lavages (p = 0.009) in patients with
      early symptoms of common cold. Pro-inflammatory mediators FGF-2, Fractalkine,
      GRO, G-CSF, IL-8, IL-1alpha, IP-10, IL-10, and IFN-alpha2 were reduced in the
      Iota-Carrageenan group. CONCLUSIONS: Iota-Carrageenan nasal spray appears to be a
      promising treatment for safe and effective treatment of early symptoms of common
      cold. Larger trials are indicated to confirm the results.

PMID- 20696084
TI  - Factors associated with pneumococcal and influenza vaccination in hospitalized
      people aged >=65 years.
AB  - Socioeconomic factors and the patterns of use of health services associated with
      influenza and pneumococcal vaccination were studied in people aged ?65 years
      admitted to three general hospitals in Spain between 2005 and 2007. The following
      data were collected: age, sex, risk of pneumonia, educational level, social
      class, type of household, physician visits, length of time with the same general
      practitioner, and influenza and pneumococcal vaccination (23vPPV). Associations
      between variables were assessed using multivariate logistic regression analysis.
      In total, 1702 patients were included; 59.9% had received 23vPPV and 65.6%
      influenza vaccine. Older age (OR 1.04, P<0.001), living with a partner (OR 1.72,
      P=0.003) and influenza vaccination during the last year (OR 6.64, P<0.001) were
      associated with 23vPPV. Male sex (OR 1.44, P=0.005), older age (OR 1.02,
      P=0.009), moderate risk of pneumonia (OR 1.58, P=0.001), living with a partner
      (OR 1.52, P=0.015) and frequent physician visits during the last year (1-6
      annuals visits (OR 2.65, P<0.001); >6 visits (OR 3.83, P<0.001)) were associated
      with influenza vaccination. Coordination between public health and primary-care
      services may be necessary to improve vaccine uptake.

PMID- 20696085
TI  - Congress in Porto September 2010 and increased impact factor.

PMID- 20696086
TI  - A 17-year review of foodborne outbreaks: describing the continuing decline in
      England and Wales (1992-2008).
AB  - Systematic national surveillance of foodborne disease outbreaks effectively
      serves the development of public health policy on food safety. The Health
      Protection Agency has maintained a collaborative surveillance system for
      foodborne outbreaks in England and Wales since 1992. Up to 2008, 2429 foodborne
      outbreaks were identified, described and analysed for changes over time.
      Salmonella spp. accounted for half of the outbreaks, although the proportion of
      these decreased over the surveillance period. Similarly, the proportion of
      outbreaks caused by Clostridium perfringens decreased, while those attributed to
      Campylobacter spp. and Vero cytotoxin-producing Escherichia coli O157 increased.
      Although poultry meat was the most frequently implicated food vehicle in
      outbreaks followed by miscellaneous foods and red meats, the proportion of
      outbreaks attributed to meats in fact decreased over time but those linked to
      miscellaneous foods did not. Over the surveillance period, the proportion of
      outbreaks linked to eggs and S. Enteritidis non-phage-type 4, particularly in
      food service establishments, increased, highlighting the importance of this
      organism/setting/vehicle association. Contributory factors in most outbreaks were
      cross-contamination, inadequate heat treatment, and inappropriate food storage.
      This study describes the overall decline in foodborne outbreaks, providing
      evidence that the introduction and adherence to effective control measures
      provide the best means of minimizing the risk of foodborne infection.

PMID- 20696087
TI  - Risk factors for fluoroquinolone resistance in Enterococcus urinary tract
      infections in hospitalized patients.
AB  - Past studies exploring risk factors for fluoroquinolone (FQ) resistance in
      urinary tract infections (UTIs) focused only on UTIs caused by Gram-negative
      pathogens. The epidemiology of FQ resistance in enterococcal UTIs has not been
      studied. We conducted a case-control study at two medical centres within the
      University of Pennsylvania Health System in order to identify risk factors for FQ
      resistance in enterococcal UTIs. Subjects with positive urine cultures for
      enterococci and meeting CDC criteria for healthcare-acquired UTI were eligible.
      Cases were subjects with FQ-resistant enterococcal UTI. Controls were subjects
      with FQ-susceptible enterococcal UTI and were frequency matched to cases by month
      of isolation. A total of 136 cases and 139 controls were included from 1 January
      2003 to 31 March 2005. Independent risk factors [adjusted OR (95% CI)] for FQ
      resistance included cardiovascular diseases [2.24 (1.05-4.79), P=0.037],
      hospitalization within the past 2 weeks [2.08 (1.05-4.11), P=0.035],
      hospitalization on a medicine service [2.15 (1.08-4.30), P<0.030], recent
      exposure to beta-lactamase inhibitors (BLIs) [14.98 (2.92-76.99), P<0.001],
      extended spectrum cephalosporins [9.82 (3.37-28.60), P<0.001], FQs [5.36 (2.20
      13.05), P<0.001] and clindamycin [13.90 (1.21-10.49), P=0.035]. Use of BLIs,
      extended spectrum cephalosporins, FQs and clindamycin was associated with FQ
      resistance in enterococcal uropathogens. Efforts to curb FQ resistance should
      focus on optimizing use of these agents.

PMID- 20696088
TI  - Diphtheria in the United Kingdom, 1986-2008: the increasing role of
      Corynebacterium ulcerans.
AB  - Diphtheria is an uncommon disease in the UK due to an effective immunization
      programme; consequently when cases do arise, there can be delays in diagnosis and
      case-fatality rates remain high. We reviewed 102 patients with infections caused
      by toxigenic corynebacteria (an average of four per year) reported in the UK
      between 1986 and 2008: 42 Corynebacterium diphtheriae, 59 C. ulcerans and one C.
      pseudotuberculosis, as well as 23 asymptomatic carriers. Five fatalities were
      reported, all in unvaccinated patients. The major risk factor for C. diphtheriae
      infection continued to be travel to an endemic country. C. ulcerans infections
      became more common than C. diphtheriae infections in the UK; they were associated
      with contact with companion animals. The occurrence of indigenous severe C.
      ulcerans infections and imported C. diphtheriae cases highlights the need to
      maintain UK routine vaccination coverage at the 95% level in the UK, as
      recommended by the World Health Organization.

PMID- 20696089
TI  - The influence of weather on community gastroenteritis in Australia.
AB  - Infectious gastroenteritis is a common illness in Australia as elsewhere. Data
      from a year-long national gastroenteritis survey in 2001-2002 showed that
      gastroenteritis was more common in the northern and hotter part of Australia.
      These data were used to quantify associations between local weather variables and
      gastroenteritis in people aged >5 years while controlling for socioeconomic
      status. A distributed lag model was used to examine the influence of weather over
      a period of days prior to an event and the maximal effect was found at a lag of 2
      5 days. The total effect over the preceding week indicated a relative increase
      from baseline in the probability of gastroenteritis of 2.48% (95% CI 1.01-3.97)
      for each degree rise ( degrees C) over that period. Given the very high burden of
      gastroenteritis, this represents a substantial effect at the population level and
      has relevance for health predictions due to climate change.

PMID- 20696090
TI  - Provision of nutritional support to those experiencing complications following
      bariatric surgery.
AB  - This review details the practicalities of providing nutrition support to obese
      patients who experience complications following bariatric surgery and highlights
      some of the nutritional challenges encountered by this group of patients.
      Bariatric surgery to treat morbid obesity has significantly increased
      internationally over the past decade with hospital admissions rising annually.
      The gastric bypass is currently the most commonly performed procedure. The
      complication rate can be up to 16%, with a considerable proportion having
      nutritional implications. The treatment can involve avoidance of oral diet and
      nutrition support, i.e. enteral or parenteral nutrition. Opposition to nutrition
      support can be encountered. It is useful to clarify the aims of nutrition
      support, these being: the avoidance of overfeeding and its consequences,
      preservation of lean body mass and promotion of healing. Evidence suggests that
      hypoenergic nutrition is not harmful and may actually be beneficial. There is a
      lack of consensus regarding the optimum method to predict the nutritional
      requirements in the obese acutely unwell patient. The literature suggests that
      the predicted equations are fairly accurate compared to measured energy
      expenditure in free living obese patients before and after bariatric surgery.
      However, these findings cannot be directly applied to those obese patients
      experiencing complications of bariatric surgery, who will be acutely unwell
      exhibiting inflammatory response. It is therefore necessary to refer to the
      literature on energy expenditure in hospitalized obese patients, to help guide
      practice. More research examining the energy and protein requirements of obese
      patients needing nutrition support following bariatric surgery is urgently
      required.

PMID- 20696091
TI  - Encouraging appropriate, evidence-based use of oral nutritional supplements.
AB  - With the considerable cost of disease-related malnutrition to individuals and to
      society (estimated to be >L13*109 for the UK, 2007 prices), there is a need for
      effective and evidence-based ways of preventing and treating this condition. The
      wide range of oral nutritional supplements that may be prescribed for the dietary
      management of malnutrition and other conditions account for only about 1% (about
      L99*106, 2007 data) of the prescribing budget in England. Systematic reviews and
      meta-analyses consistently suggest that ready-made, multi-nutrient liquids which
      may be prescribed can improve energy and nutritional intake, body weight and have
      a variety of clinical and functional benefits in a number of patient groups. Meta
      analyses have repeatedly shown that oral nutritional supplements produce
      significant reductions in complications (e.g. infections) and mortality, and a
      recent meta-analysis shows a reduction in hospital admissions (OR 0.56 (95% CI
      0.41, 0.77), six randomised controlled trials). Such benefits suggest that the
      appropriate use of oral nutritional supplements should form an integral part of
      the management of malnutrition, particularly as there is currently a lack of
      evidence for alternative oral nutrition strategies (e.g. food fortification and
      counselling). As with all therapies, compliance to oral nutritional supplements
      needs to be maximised and the use monitored. To make sure that those at risk of
      malnutrition are identified and treated appropriately, there is a need to embed
      national and local policies into routine clinical practice. In doing so, the
      economic burden of this costly condition can be curtailed. As recently suggested
      by the National Institute for Health and Clinical Excellence, substantial cost
      savings could be made if screening and treatment of malnourished patients was
      undertaken.

PMID- 20696092
TI  - Drug disposition in obesity and protein-energy malnutrition.
AB  - Clinical response to medication can differ between patients. Among the known
      sources of variability is an individual's nutrition status. This review defines
      some pharmacokinetic terms, provides relevant body size metrics and describes the
      physiologic influences of protein-energy malnutrition and obesity on drug
      disposition. Weight-based drug dosing, which presumes a healthy BMI, can be
      problematic in the protein-energy malnourished or obese patient. The use of total
      body weight, lean body weight, or an adjusted body weight depends on the drug and
      how it is differently handled in malnutrition or obesity. Most of the recognized
      influences are seen in drug distribution and drug elimination as a result of
      altered body composition and function. Distribution characteristics of each drug
      are determined by several drug-related factors (e.g. tissue affinity) in
      combination with body-related factors (e.g. composition). Drug elimination occurs
      through metabolic and excretory pathways that can also vary with body
      composition. The current data are limited to select drugs that have been reported
      in small studies or case reports. In the meantime, a rational approach to
      evaluate the potential influences of malnutrition and obesity can be used
      clinically based on available information. Antimicrobials are discussed as a
      useful example of this approach. Further advancement in this field would require
      collaboration between experts in body composition and those in drug disposition.
      Until more data are available, routine monitoring by the clinician of the protein
      energy malnourished or obese patient receiving weight-based drug regimens is
      necessary.

PMID- 20696093
TI  - Does eating local food reduce the environmental impact of food production and
      enhance consumer health?
AB  - The concept of local food has gained traction in the media, engaged consumers and
      offered farmers a new marketing tool. Positive claims about the benefits of local
      food are probably not harmful when made by small-scale producers at the local
      level; however, greater concern would arise should such claims be echoed in
      policy circles. This review examines the evidence base supporting claims about
      the environmental and health benefits of local food. The results do not offer any
      support for claims that local food is universally superior to non-local food in
      terms of its impact on the climate or the health of consumers. Indeed several
      examples are presented that demonstrate that local food can on occasions be
      inferior to non-local food. The analysis also considers the impact on greenhouse
      gas emissions of moving the UK towards self-sufficiency. Quantitative evidence is
      absent on the changes in overall emissions that would occur if the UK switched to
      self-sufficiency. A qualitative assessment suggests the emissions per item of
      food would probably be greater under a scenario of self-sufficiency than under
      the current food system. The review does not identify any generalisable or
      systematic benefits to the environment or human health that arise from the
      consumption of local food in preference to non-local food.

PMID- 20696094
TI  - Metabolic and hormonal aspects of polycystic ovary syndrome: the impact of diet.
AB  - Polycystic ovary syndrome (PCOS) is a common, chronic endocrine condition
      affecting young women of reproductive age. It is characterised by
      hyperandrogenaemia, and profound menstrual and ovulatory dysfunction with
      consequent sub-fertility. A clustering of metabolic aberrations is commonly
      associated with this condition and these include insulin resistance, disordered
      lipid metabolism and chronic low-grade inflammation. Overweight and obesity, as
      well as a degree of adipose tissue dysfunction, are present in a large proportion
      of women with PCOS, and where present, magnify the inherent hyperandrogenaemia
      characteristic of the condition, in addition to worsening the metabolic profile.
      Diet and lifestyle interventions are among the first-line treatments for PCOS,
      and weight reduction through energy restriction has been shown to exert positive
      influences on both metabolic and hormonal aspects of this condition. Alterations
      in carbohydrate amount and type have also been investigated, and more recently,
      dietary fatty acids, with a particular emphasis on PUFA, have been shown to have
      a positive impact within this population group. Although it is likely that diet
      is not the root cause of PCOS, it represents a modifiable variable with the
      potential to improve the health of women with this condition. Work to date has
      provided insights into the role of diet in PCOS; however, further work is
      required to determine the role of nutrients specifically within the context of
      PCOS, in order to develop more effective, evidence-based dietary guidelines for
      this condition.

PMID- 20696095
TI  - Population genetic structure of the prairie dog flea and plague vector, Oropsylla
      hirsuta.
AB  - Oropsylla hirsuta is the primary flea of the black-tailed prairie dog and is a
      vector of the plague bacterium, Yersinia pestis. We examined the population
      genetic structure of O. hirsuta fleas collected from 11 prairie dog colonies, 7
      of which had experienced a plague-associated die-off in 1994. In a sample of 332
      O. hirsuta collected from 226 host individuals, we detected 24 unique haplotype
      sequences in a 480 nucleotide segment of the cytochrome oxidase II gene. We found
      significant overall population structure but we did not detect a signal of
      isolation by distance, suggesting that O. hirsuta may be able to disperse
      relatively quickly at the scale of this study. All 7 colonies that were recently
      decimated by plague showed signs of recent population expansion, whereas 3 of the
      4 plague-negative colonies showed haplotype patterns consistent with stable
      populations. These results suggest that O. hirsuta populations are affected by
      plague-induced prairie dog die-offs and that flea dispersal among prairie dog
      colonies may not be dependent exclusively on dispersal of prairie dogs. Re
      colonization following plague events from plague-free refugia may allow for rapid
      flea population expansion following plague epizootics.

PMID- 20696096
TI  - Density-dependent effects on parasite growth and parasite-induced host
      immunodepression in the larval helminth Pomphorhynchus laevis.
AB  - Larval helminths exploit the physiology of their intermediate hosts: first, as a
      resource for energy and space and second by altering the immune system activity
      to ensure their survival. Whereas the growth pattern under parasite competition
      has been investigated, the effect of multiple infections on the level of parasite
      induced immunodepression in a trophically transmitted helminth has been
      neglected. In this study, amphipods Gammarus pulex were infected in the
      laboratory by the acanthocephalan Pomphorhynchus laevis to investigate how
      parasite density in the intermediate host affected (i) cystacanth growth and (ii)
      the level of parasite-induced alterations of the host immune defences, two traits
      strongly linked to host exploitation. The study highlights that sharing a host is
      costly. As parasite intensity increases, competition for resources translates
      into a reduction in cystacanth volume. Immune manipulation is also modulated by
      density. Interestingly, immunodepression is higher in double-infected hosts
      compared to hosts with a single infection, suggesting an opportunity for
      cooperative immune manipulation. However, in higher multiple infections,
      parasites do not further down-regulate the host immune response, possibly to
      avoid additional costs that may outweigh the benefits of immunodepression.

PMID- 20696097
TI  - High-throughput screening in suboptimal growth conditions identifies agonists of
      Giardia lamblia proliferation.
AB  - Giardia lamblia is one of the most prevalent parasites of mankind and is
      estimated to cause over 200 million infections per year. To screen chemical
      libraries for compounds that perturb trophozoite proliferation we adapted a
      conventional culture method to 384-well plates and identified numerous
      inhibitors. Here we used a modified assay to screen for compounds that promote
      trophozoite multiplication. Trophozoite growth was reduced by dilution of the
      culture medium and the growth period was extended to screen 2 compound libraries
      comprising 1500 compounds. A total of 4 agonists of trophozoite multiplication
      were identified. In the presence of one of these compounds, strychnine, enhanced
      growth was accompanied by unusual trophozoite morphology characterized by
      dividing trophozoites displaying more than the 2 nuclei per cell which are
      normally observed. The other agonists, although belonging to 2 distinct chemical
      groups, are known to affect isoprenylation, indicating a link between protein or
      lipid isoprenylation and growth in culture. Although inhibitors of isoprenylation
      are known to antagonize proliferation of mammalian cells, an agonistic effect of
      isoprenylation modulators has to our knowledge not been described previously.
      These observations illustrate the power of chemical genetics for identifying
      pathways controlling specific traits in G. lamblia.

PMID- 20696098
TI  - [Bone tissue as an endocrine gland].
AB  - Bone tissue was essentially considered as a mechanical structure; however is now
      well known that is the site of permanent bone remodelation. In addition, bone
      functions as an endocrine gland producing osteocalcin, which in turn interacts
      with other tissues, such as fat, pancreas and gastrointestinal tract. As a
      consequence, osteocalcin intervenes into glucose metabolism, peripheral insulin
      sensitivity and inflammatory process. In sum, bone may be accepted as an
      endocrine gland.

PMID- 20696099
TI  - [Chronic diseases and neoplasms, a view from complex sciences and primary care].
AB  - 80% of adults older than 65 years have at least one chronic, degenerative or
      neoplasm disease (CDND). The health care cost is high, and they represent the
      main causes that affect the quality of life. From the scope of the complexity
      sciences, the CDND are common problems of health but their study and solutions
      are complex and difficult. One strategy for preventing and treating them is to
      identify "the weak corner," the causal factors or the ordering parameter as the
      relevant point of intervention. The evidence shows that 80% of the CDND could be
      prevented with primary care actions like immunizations and lifestyle changes.

PMID- 20696100
TI  - [Relationship between sex steroids and bone density in elderly men].
AB  - OBJECTIVE: To determine the relationship between serum estradiol level (ESL) and
      testosterone serum level (TSL) with bone mineral density (BMD) in elderly men.
      METHODS: Cross-sectional study including 127 healthy men aged 60 years and over.
      BMD of the lumbar spine and femoral neck were measured. ESL, TSL and sex hormone
      binding globulin were estimated by radioimmunoassay. Free testosterone level
      (FTL) was calculated. RESULTS: The ESL and BMD correlation at the spine was r =
      0.288, (p < 0.01) and at the femoral neck was r = 0.224, (p < 0.01). These
      correlations remained significant after adjustment for BMI and age. By contrast,
      no correlation was found between TSL and BMD. However FTL were associated with
      BMD at the spine (r = 0.288, p < 0.01) and at the femoral neck (r = 0.190, p <
      0.05). CONCLUSIONS: ESL and FTL are associated with BMD in elderly men. This
      effect may be partially mediated by the peripheral conversion of testosterone
      into estradiol.

PMID- 20696101
TI  - [Dental caries prevalence survey in children and teenagers].
AB  - OBJECTIVE: To identify the prevalence of caries in affiliated children and
      teenagers at Instituto Mexicano del Seguro Social (IMSS). METHODS: The survey was
      carried out according to the World Health Organization indexes. The studied was
      carried out in 1545 boys and girls aged three, five, six, and twelve years and
      selected by stratified random sampling in seven places of Mexican Republic
      (Guanajuato, East and West Estado de Mexico, Northwest 1, Northeast 2, Southwest
      3, and Southeast 4 DF). RESULTS: The prevalence of caries was 66.9 %. Rates were
      higher in temporary dentition than in permanent teeth (p < 3.07). The mean of
      caries index per tooth in primary dentition in children of six years of age was
      3.57 +/- 2.8. In the 12 years of age group the average per tooth was 1.97 +/-
      1.4. The main component in both primary and permanent dentition was caries with
      2.49 and 1.56 respectively. CONCLUSIONS: The results of this survey showed slight
      changes in prevalence and high levels of caries in children.

PMID- 20696102
TI  - [Left ventricular dysfunction measured in diabetic patients with chronic renal
      failure on continuous ambulatory peritoneal dialysis].
AB  - BACKGROUND: In diabetic patients with chronic renal failure (CRF) treated with
      dialysis, the diastolic and systolic left ventricular dysfunction is frequent.
      The aim was to assess by echocardiography the prevalence of diastolic and
      systolic ventricular dysfunction in diabetic patients with CRF treated with
      continuous ambulatory peritoneal dialysis (CAPD). METHODS: Sixty diabetic
      patients with CRF in CAPD were studied. The mean age was 54.5 +/- 12 years (27-78
      years). The left ventricular filling pattern (LVFP) as a diastolic function
      parameter and left ventricular ejection fraction (LVEF) as a systolic function
      parameter were measured by transthoracic echocardiography. Descriptive
      statistical analysis was used. RESULTS: 27 (45 %) patients were women and 33 (55
      %) were men. In 55 (91.7 %) left ventricular concentric hypertrophy was observed.
      Fifty-two patients (86.7 %) showed LVFP type I; three (5 %) had the type II; two
      (3.3 %) showed pseudonormal pattern and three (5 %) had a normal LVFP. The LVEF
      was 0.63 +/- 0.09 (CI = 0.41-0.82). Forty nine (81.7 %) patients had LVEF equal
      or greater than 0.55. CONCLUSIONS: The prevalence of diastolic left ventricular
      dysfunction was 95 % and the prevalence of systolic left ventricular dysfunction
      was 18.3%.

PMID- 20696103
TI  - [Body aesthetic model, body dissatisfaction and disordered eating in
      adolescents].
AB  - OBJECTIVE: To identify the relationship between the ideal aesthetic body shape
      model, body dissatisfaction and disordered eating in adolescent women. METHODS: A
      cross-sectional analytic design research was carried out in a sample of 257, 15
      to 19 year old female high school students. Data were compiled with the Brief
      Questionnaire for Risky Eating Behaviors (BQREB), the Visual Scale of Body
      Satisfaction for adolescents and the Sociocultural Influences on the Aesthetic
      Body Shape Model Questionnaire (ABSMQ). RESULTS: 8.3 % of participants were high
      scorers for the BQREB, from the restrictive type mainly. The ABSMQ subscales
      positively correlated with body dissatisfaction and risky eating behaviors, the
      strongest being body image dissatisfaction. CONCLUSIONS: The influence of
      publicity and social models, were found to be related to body image
      dissatisfaction and to eating disorder among the adolescents from the sample.

PMID- 20696104
TI  - [Acromegaly treatment with octreotide LAR in 42 cases].
AB  - OBJECTIVE: To evaluate the efficacy of octreotide (OCT) LAR in patients with
      acromegaly. METHODS: Observational, retrospective, transversal and descriptive
      study was done. Forty two patients with acromegaly (recently diagnosed and who
      have undergone surgery but not cured) followed up for 24 weeks were studied.
      There were 14 males (30 %) and 28 females (70 %) with an average age of 44
      (range: 18-67 years). Dose adjustments of 10, 20 and 30 mg were made. RESULTS:
      OCT LAR was administered in 24 patients who had been operated without cure and in
      18 newly diagnosed patients. At 24 weeks of treatment in those patients not
      operated, GHm decreased 56 % and IGF-1 decreased 30 %. In patients who were
      operated but not cured, GHm decreased 49 % and IGF-1 decreased 53 %. For
      microadenomas, GHm decreased 57.6 % and IGF-1 60 %. For macroadenomas, decrease
      was 50 % and 37 %, respectively. The efficacy of OCT LAR on microadenomas,
      success was achieved (total and partial) in 65 % of patients and in 28 % of
      patients with macroadenomas. CONCLUSIONS: Patients with microadenomas and with
      lesser hypersomatotropinemia have a better response to treatment.

PMID- 20696105
TI  - [Bicentennial and centennial commemoration of Mexican medicine].

PMID- 20696106
TI  - [Epidemics and diseases during the Independence period in Mexico].
AB  - The epidemics and endemic diseases in Mexico were not a problem before the
      Independence period. Hunger was less than in the past. The 1806 Influenza
      epidemics had been forgotten. Measles was considered a benign illness. In 1810,
      there was an increase in the number of cases of black vomit in Veracruz. Sixty
      percent of 541 hospitalized patients die of the disease. In 1812, an outbreak of
      yellow fever spread from Veracruz to Jalapa accompanying the movement of troops
      and killing over 300 soldiers of the Castilla's Battalion. The appearance of
      petechial fever, maybe typhus marketed in 1813 the onset of the most important
      epidemics. The preceding was the indirect effect of war: diseases of prisons and
      military quarters which became overwhelming in times where the movements of
      troops and of important groups of populations along with crowing, loss homes,
      hunger and bad hygiene habits. There was also Influenza or "pestilent cold."
      Measures of detection and quarantine were taken. "Naranjate" mixed with tartaric
      cremor was used against fever. Fumigation with nitric acid and burners, where
      they incinerated gun powder were among the health protection policies. It is
      noteworthy the advance and relief provided by the introduction of smallpox
      vaccine, the only preventive mean useful against smallpox which was a
      breakthrough in public health.

PMID- 20696107
TI  - [The transcription factor NF-kappaB in human diseases].
AB  - The transcription nuclear factor kappa B (NF-kappaB) was first described in 1986.
      Currently, the NF-kappaB has been linked to several metabolic and inflammatory
      diseases as well as to several types of cancer. NF-kappaB will continue to be of
      interest in many disease processes such as inflammatory, infectious and
      neoplastic. The discovery of this factor has increased our knowledge about the
      regulation of inflammation and chronic diseases, as well as the medications used
      to treat those diseases.

PMID- 20696108
TI  - [Mexican physicians perception about hormonal therapy after the Women's Health
      Initiative Study].
AB  - BACKGROUND: The medical opinion after WHI study has changed. The aim was to know
      the opinion of Mexican physicians about hormone therapy (HT) after the WHI study.
      METHODS: We gave 14 questions to 463 physicians to assess their opinion of HT
      according to risks, benefits, doses, indications and contraindications.
      Descriptive statistics were used for data analysis. RESULTS: Only 31 % begin HT
      after 60 years of age and 74 % considered that HT decreased osteoporosis risk; 73
      % use progestin in women with a uterus. 82 % did not believe that estrogen
      progestin HT increased the possibility of endometrial cancer and 51 % believed
      that breast cancer possibility increased. The main indication for HT prescription
      was for bone loss diminution (51 %); 88 % considered that low dose HT was as
      effective as conventional dose. CONCLUSIONS: The use of HT has been modified by
      Mexican physicians after the WHI study.

PMID- 20696109
TI  - [Usefulness of a clinical questionnaire for screening osteopenia and osteoporosis
      in post-menopausal women].
AB  - BACKGROUND: The prevalence of osteoporosis in post-menopausal women (PMW) is 30
      %, and bone densitometry (BD) is the gold standard. This is not recommended as a
      screening test because of its cost. Instead, the SCORE index (Simple Calculated
      Osteoporosis Risk Estimation) is proposed. The objective is to determine the
      sensitivity and specificity of this test in the population and the optimization
      of BD. METHODS: The SCORE Index is a pre-screening questionnaire; it was used in
      PMW to compare with BD, registering the total score of the questionnaire,
      densitometry diagnosis, the fracture risk and the site of osteoporosis. The
      sensitivity and specificity of SCORE Index and chi(2) of Mantel-Hanszel were
      calculated. RESULTS: We studied 201 patients, mean age 55.70 years. Osteoporosis
      was recognized in 22.8 %, osteopenia in 68.3 % and 8.9 % was normal. The
      sensitivity of the SCORE index was 87 % (95 % CI = 77-97) and specificity was
      34.6 % (95 % CI = 27-42) with p = 0.000. A positive probability quotient of 1.33
      (95 % CI = 1.1-1.7). CONCLUSIONS: Osteoporosis is a frequent disease in PMW. It
      is mandatory to have cheap and easy-tools which can detect osteoporosis cases.

PMID- 20696110
TI  - [Epidemiological characteristics of depressed Mexican pregnant women].
AB  - OBJECTIVE: To estimate the prevalence of depression in pregnant women, the
      epidemiological characteristics and associated factors. METHODS: A cross
      comparison, with a sample of 220 pregnant women between 18 and 32 weeks
      gestation. We excluded patients with depression six months before the current
      pregnancy. RESULTS: Depressed women were 6.4 %, mean age 26 years and 21.4 % were
      adolescent. The majority women were high school students (50 %); 71.4 % belong to
      a low medium socioeconomic status; 21.4 % were without a partner; 35.7 % had
      depression history in the family and 28.6 % had a history of prior antidepressant
      treatment. CONCLUSIONS: The prevalence of depression in Mexican pregnant women
      was low. Risk factors associated to depression were young age, low socio
      economical status, a lack of a partner, a history of depression in the family.

PMID- 20696111
TI  - [Bilateral tonsillar hypertrophy as the first manifestation of B cell-small
      lymphocytic lymphoma with interfolicular pattern].
AB  - B-cell small lymphocytic lymphoma typically involves nodal or extranodal tissues
      as a diffuse proliferation with proliferation centers (pseudofollicules)
      obliterating normal architecture. But there are unusual patterns of involvement
      including interfollicular pattern that can be difficult to recognize
      histologically and probably represent partial or early involvement by neoplasm.
      Tonsillar lymphoma usually presents either as a unilaterally enlarged palatine
      tonsil or as an ulcerative and fungating lesion over the tonsillar area. Most
      lymphomas that involve the tonsil are diffuse large B cell lymphomas and primary
      low-grade lymphomas are exceptional. We present a primary B-cell small
      lymphocytic lymphoma affecting palatine tonsils with interfollicular pattern in a
      54 year-old man that clinically presented with symmetric / bilateral tonsillar
      enlargement and sleep apnea.

PMID- 20696112
TI  - [Poland's syndrome. Case report].
AB  - OBJECTIVE: To report a case of Poland syndrome in a 67-year-old woman. CLINICAL
      CASE: The patient was questioned and examined for a history of malformations
      characteristic of this syndrome on a routine medical visit. Thorax, bone thorax,
      and comparative hand X-ray were taken. Mammary ultrasound, mastography, and
      computed axial tomography were taken also. The right hemithorax showed a thin
      subcutaneous cell tissue. Axillary alopecia, mammary hypoplasia and areola-nipple
      complex retraction, hypoplasia of major pectoral muscles was observed. In the
      right upper limb, there was forearm shortening, hypoplasia of the second phalanx
      in all five fingers, and absence of distal phalanx in the index finger.
      CONCLUSIONS: The patient showed 4 out of the 5 characteristics considered as
      typical by Hester and Bostwick. In terms of hand anomalies, she was classified as
      type 1 according to Gausewitz and according with Al-Qaifan, the patient belongs
      to type 2.

PMID- 20696113
TI  - [Treatment with imiquimod and surgical excision of a patient with extramammary
      Paget's disease. Case report].
AB  - Extramammary Paget's disease (EMPD) is a less common cutaneous type of cancer. It
      presents as erythematous plaques most frequently located in the genital region,
      perianal skin, and other cutaneous sites rich in apocrine glands, but it also may
      originate from keratinocytic stem cells. Recently, imiquimod has been used for
      the management of primary or relapsing extramammary Paget's disease. Complete
      healing, without recurrence, of extramammary Paget's disease in patients whom
      were treated topically with 5 % imiquimod cream was observed. We report a 78 year
      old patient with scrotal and perianal extramammary Paget's disease treated with
      imiquimod cream in both lesions and subsequently with surgical excision in
      scrotum for the management of relapsing disease.

PMID- 20696114
TI  - [The physician's humanizing role. Philosophical view of socio-anthropological
      work in medicine].
AB  - The paper presents a critical analysis of current society making emphasis on the
      human needs to generate domain among equals, as well as the sense of competition
      and division that this creates. It addresses the process of dehumanization that
      the same civilization has generated focusing on laboral paradigm of our days and
      the weak social justice that unequal wealth distribution has generated. It has
      been seen that health professionals involved in such context, have not escaped
      socio-cultural pressure and postmodern neo-liberal position. The paper discusses
      about the humanizing role health professionals have in society, and the relevance
      of the philosophical exercise in their acts above human frailty. Finally, it is
      suggested an alternative for repositioning to himself and society.

PMID- 20696115
TI  - [Quality of life related to public health and the health system reflections].
AB  - Quality of life (QL) is used to measure the well-being of the individual, the
      population and the quality of the health system. The QL related to the health has
      three approaches: To identify the perception of the individual on the way the
      disease affects the QL; to evaluate the effect of a treatment on the physical,
      emotional and well-being of the individual and to identify the necessities for
      health of the population. The aim is to evaluate publications on QL, and its use
      for evaluation of the health. Forty two studies were evaluated (2002-2008) on QL,
      21 (50 %) were related to methodological and conceptual aspects or to describe
      instruments for evaluation; 13(31 %) were related to research work using
      questionnaires and 8(19 %) to projects that used specific forms. The integration
      of research groups must be encouraged related to QL in healthy groups, as well as
      in groups carrying problems of health; to evaluate the damage and the impact of
      the health intervention through controlled clinical trials. Because the affection
      of the population with a disease has effect on the psychological and social
      domains, the need for a multidisciplinary equipment to attend health, where the
      educative aspect acquires a preponderant role is suggested.

PMID- 20696116
TI  - [Description of a U.S. emergency department and its patient population during a
      year].
AB  - INTRODUCTION: In the United States, Emergency Medicine (EM) is recognized as an
      independent medical speciality, which focuses on the initial evaluation and
      treatment of all patients with acute illness or injury. Patients have free access
      to the emergency department (ED), which serves as the main portal of entry for
      most acute patients coming into the hospital. The ED is staffed with EM
      specialists at all hours. The purpose of this study was to describe a U.S.
      tertiary care hospital ED and the patient population that is cared for there.
      MATERIAL AND METHODS: A descriptive retrospective study of the patient population
      at Beth Israel Deaconess Medical Center Emergency Department, from 1 January to
      31 December 2003. Demographic data were collected for each patient, as well as
      estimated severity index score, diagnosis and ED disposition. RESULTS: 46,936
      patients with a median age of 46.5 years where seen at the ED in 2003. Women
      represented 56%. The majority of patients had an ESI triage score = 3. All of the
      main categories of ICD-9 diagnostic codes where represented among patients' ED
      discharge diagnoses. 65% of ED patients where discharged home from the
      department. Approximately one third where admitted to the hospital. CONCLUSION: A
      broad range of patients are seen in the ED, which sets high demands for the
      knowledge and skills of the ED staff as well as co-operation between the ED and
      other specialties and hospital departments.

PMID- 20696117
TI  - [New European model for cross-sectorial health initiatives].
AB  - Over the last years EU have been working on the development of a common
      classification system for health indicators. In connection with prevention and
      health promotion, a classification system has now been developed: the European
      Health Promotion Indicator Development, EUHPID. The purpose has been to establish
      a system of indicators to advance the focus on health promotion. Furthermore, the
      EUHPID can be used as a planning tool to generate higher consistency between
      different health promotion initiatives and other policy initiatives. This article
      discusses the model and its relevance in a Danish context.

PMID- 20696118
TI  - [Naturally occurring oseltamivir resistance in influenza A].
AB  - During the last two influenza seasons, one of the predominant influenza A types
      (H1N1) has developed complete resistance to oseltamivir, the primary treatment
      option. The virus does, however, remain sensitive to zanamavir and amantadine.
      There is no unequivocal explanation for this slide in the development of
      resistance. The best prevention strategy remains vaccination of the general
      population to avoid immunity. Future antiviral treatment calls for knowledge
      about resistance to existing types of influenza and the availability of all three
      types of antiviral medication.

PMID- 20696119
TI  - [Laparoscopic subtotal cholecystectomy for complicated gallstone conditions].
AB  - In laparoscopic cholecystectomy conversion to open surgery occurs. Patients who
      would otherwise need conversion can benefit from laparoscopic subtotal
      cholecystectomy (LSC). We present a review of studies in which outcome after LSC
      has been investigated. The results show reduced conversion rates, shorter
      hospital stay, minimal complications and mortality rates. Acute cholecystitis,
      cirrhosis, Mirrizi syndrome type I are the indications for LSC. Randomized
      prospective trials are needed to investigate safety and long-term effects.

PMID- 20696120
TI  - [Possible daptomycin-induced organizing pneumonia].
AB  - We report a possible and rare case of drug-induced organizing pneumonia in a
      patient receiving daptomycin. A 75-year-old man with acute infective aorta valve
      endocarditis due to Enterococcus faecalis developed organizing pneumonia
      following treatment with intravenous daptomycin and ceftriaxone. The patient
      could have acquired an infectious agent which was resistant to ceftriaxone, such
      as Legionella, and he was thus treated with ciprofloxacin and rifampicin.
      However, no antigen was found in the urine, and the patient's symptoms subsided
      after daptomycin was discontinued.

PMID- 20696121
TI  - Small fibre impairment predicts neuropathic pain in Guillain-Barre syndrome.
AB  - The mechanisms of neuropathic pain (NP) in Guillain Barre syndrome (GBS) are
      currently unknown. It has recently been shown that acute neuropathy of GBS not
      only affects large myelinated fibres but also small nociceptive fibres. In this
      prospective longitudinal 18 months study, we investigated the role of small fibre
      impairment in NP in GBS (n=30). Small fibres were assessed by quantifying cold
      and warm detection and pain thresholds and responses to suprathreshold painful
      thermal and mechanical stimuli. Nerve conduction velocities and mechanical
      detection thresholds assessed large myelinated fibres. Detection thresholds
      particularly at the lower limbs were significantly impaired in patients with GBS
      compared to 15 healthy controls. GBS patients with NP (n=13) had more severe
      impairment of cold detection thresholds (p=0.04), heat pain thresholds (p=0.03)
      and responses to suprathreshold heat stimuli (p=0.017) in the foot compared with
      those without pain or with non-neuropathic pain (n=17). Large fibre dysfunction
      and motor disability were similar between groups. Small fibre sensory impairment
      at the acute stage was correlated with the intensity of burning pain (Rho: -0.72;
      p=0.01 for cold detection; Rho: 0.72; p=0.02 for heat pain) and predicted
      residual NP (odds 4.1 p=0.04 for heat pain). These findings emphasize the
      importance of nociceptive fibre impairment in NP in GBS at both acute and chronic
      stages and suggest similarities between the mechanisms of NP in GBS and those of
      small fibre painful sensory polyneuropathies.

PMID- 20696122
TI  - Experimental canine leishmaniasis: clinical, parasitological and serological
      follow-up.
AB  - Canine leishmaniasis (CanL) caused by Leishmania infantum is transmitted by the
      bite of phlebotomine sand flies and affects millions of dogs in Europe, Asia,
      North Africa and South America. Canis familiaris is the major host for these
      parasites, and the main reservoir for human visceral infection. The development
      of effective molecules for therapy and immunoprophylaxis, would be an important
      tool in the control of this zoonosis. The aim of this study was to characterize
      an experimental CanL model in order to determine the best challenge model and
      which parameters are the most reliable to evaluate the efficacy of new drugs or
      vaccine candidates against L. infantum infection. The intravenous challenge with
      purified amastigotes used in this study allowed the development of infection in
      all animals inoculated (as confirmed by the detection of parasite in the
      different tissues and organs collected 6 months after inoculation). Molecular and
      serologic techniques were efficient methods for the follow-up. Lymph node and
      bone marrow aspirates were suitable clinical samples to detect the presence of
      Leishmania parasites. Despite ELISA was highly sensitive in detecting specific
      anti-Leishmania antibodies the use of two tests can improve the sensitivity and
      specificity of serological diagnosis.

PMID- 20696123
TI  - A competitive binding study of chemokine, sulfated receptor, and
      glycosaminoglycan interactions by nano-electrospray ionization mass spectrometry.
AB  - Chemokines are secreted proteins that play roles in inducing chemotaxis,
      extravasation, and activation of leukocytes associated with inflammatory or
      homeostatic processes. Tyrosine sulfation of the chemokine receptor has been
      shown to be important for binding and signaling. We have applied a mass
      spectrometry method to measure the contribution of this posttranslational
      modification to binding of its ligand chemokine. Using nano-electrospray time-of
      flight mass spectrometry (nano-ESI TOF MS), we determined the association
      constants of C-C motif chemokine 7 (CCL7) with C-C chemokine receptor type 2
      (CCR2), monosulfated CCR2, and disulfated CCR2 peptides to be 1.1*10(4)M(-1),
      3.9*10(4)M(-1), and 4.0*10(5)M(-1), respectively. To our knowledge, this is the
      first reported association constant measurement between a protein and sulfated
      peptide using MS. Furthermore, nano-ESI MS was used to characterize noncovalent
      binding interactions among CCL7, Arixtra (a pentasaccharide glycosaminoglycan
      [GAG] analog), and disulfated CCR2 peptide. A lack of observable ternary complex
      formation prompted investigation of competitive binding. Results of this study
      suggest that CCR2 competes partially with GAG for CCL7 binding and that
      disulfated CCR2 peptide has a higher binding affinity than Arixtra, which
      correlates with data from association constant measurements for CCL7-disulfated
      CCR2 and CCL7-Arixtra.

PMID- 20696124
TI  - Development of a dot-blot assay for screening monoclonal antibodies to low
      molecular-mass drugs.
AB  - Dot-blot is a versatile and simple analysis to perform. We adapted this method as
      a simple identity test for monoclonal antibodies to a number of small compounds:
      three transplant drugs, an anticonvulsant, a steroid, an anticancer drug, and an
      antibiotic. Immunology-based identity tests using low-molecular-mass organic
      compounds have historically been a challenge to develop. We modified the
      traditional dot-blot assay to serve as an identity test for monoclonal antibodies
      to carbamazepine, sirolimus, tacrolimus, cyclosporine, cortisol, methotrexate,
      and gentamicin. The primary obstacle was the immobilization of these organic
      compounds on nitrocellulose as nitrocellulose is also soluble in most of the
      organic solvents in which the compounds are soluble. We evaluated different
      membranes, solvents, and chemical forms of these organic compounds to overcome
      this challenge. A number of incubation and washing solutions were also
      investigated. By varying the chemical form, concentration, and incubation
      conditions, a set of effective and reproducible identity tests were developed for
      these monoclonal antibodies.

PMID- 20696125
TI  - Detection of microRNAs in dried serum blots.
AB  - We observed the preservation of microRNAs in unrefrigerated dried serum blots.
      Preservation was not adversely affected by drying or storing at 37, 45, or 60
      degrees C instead of room temperature, but it was harmed when blots were dried
      incompletely before storage. Preservation of microRNAs in serum was not
      diminished if, instead of being kept frozen at -80 degrees C, it was stored as
      dried blots at room temperature for 5 months or at 37 degrees C for 4 weeks.
      Thus, dried blots can be a convenient and safer way to save, transport, and store
      serum for microRNA assays.

PMID- 20696127
TI  - Highly sensitive recombinant antibodies capable of reliably differentiating heart
      type fatty acid binding protein from noncardiac isoforms.
AB  - During recent times, heart-type fatty acid binding protein (hFABP) has gained
      increasing credence as a promising cardiac biomarker. This is largely due to its
      rapid myocardial release and subsequent clearance kinetics, which are superior to
      those of myoglobin and offer an earlier diagnostic window than the troponins.
      Realization of its full diagnostic and prognostic potential is dependent on
      accessibility to robust hFABP-specific assays. Here we describe a rational
      strategy for generation and screening of hFABP-specific avian-derived recombinant
      antibodies. These antibodies were confirmed to be exquisitely specific for hFABP,
      with no cross-reactivity observed in a representative panel of the most
      homologous non-heart-type FABP isoforms. All of the antibodies tested exhibited
      single-figure nanomolar affinities, and their analytical potential was
      demonstrated in a simple inhibition enzyme-linked immunosorbent assay (ELISA)
      format that returned an impressive limit of quantitation (LOQ) value of 1.9
      ng/ml. The cumulative results underline the potential value of these antibodies
      as enabling reagents for use in a variety of immunodiagnostic configurations.

PMID- 20696126
TI  - An optimized magnetite microparticle-based phosphopeptide enrichment strategy for
      identifying multiple phosphorylation sites in an immunoprecipitated protein.
AB  - To further improve the selectivity and throughput of phosphopeptide analysis for
      the samples from real-time cell lysates, here we demonstrate a highly efficient
      method for phosphopeptide enrichment via newly synthesized magnetite
      microparticles and the concurrent mass spectrometric analysis. The magnetite
      microparticles show excellent magnetic responsivity and redispersibility for a
      quick enrichment of those phosphopeptides in solution. The selectivity and
      sensitivity of magnetite microparticles in phosphopeptide enrichment are first
      evaluated by a known mixture containing both phosphorylated and nonphosphorylated
      proteins. Compared with the titanium dioxide-coated magnetic beads commercially
      available, our magnetite microparticles show a better specificity toward
      phosphopeptides. The selectively-enriched phosphopeptides from tryptic digests of
      beta-casein can be detected down to 0.4 fmol MUl-1, whereas the recovery
      efficiency is approximately 90% for monophosphopeptides. This magnetite
      microparticle-based affinity technology with optimized enrichment conditions is
      then immediately applied to identify all possible phosphorylation sites on a
      signal protein isolated in real time from a stress-stimulated mammalian cell
      culture. A large fraction of peptides eluted from the magnetic particle
      enrichment step were identified and characterized as either single- or
      multiphosphorylated species by tandem mass spectrometry. With their high
      efficiency and utility for phosphopeptide enrichment, the magnetite
      microparticles hold great potential in the phosphoproteomic studies on real-time
      samples from cell lysates.

PMID- 20696129
TI  - Mitochondrial protein import machineries and lipids: a functional connection.
AB  - Protein trafficking and translocation are essential processes in even the
      simplest living cells. The compartmentalisation within eukaryotic cells places a
      very high demand on the fidelity of protein trafficking and translocation, since
      a large percentage of the cell's protein complement is inserted into, or
      translocated across membranes. Indeed, most mitochondrial proteins are imported
      from the cytosol into the organelle and reach their final destination with the
      assistance of versatile translocation machineries. The first components involved
      in mitochondrial protein import were identified about 20years ago and over the
      last two decades many new factors and machineries have been brought to light.
      However, in spite of these discoveries we still have much to explore regarding
      the molecular mechanisms that distinguish the different mitochondrial import
      pathways. In particular, an open question that requires deeper exploration is the
      role of lipids and lipid modifying enzymes in this process. Mitochondrial
      biogenesis requires the coordinated synthesis and import of both proteins and
      phospholipids, however, these have typically been considered as distinct research
      fields. Recent findings have placed phospholipids at the forefront of research
      dealing with mitochondrial biogenesis, in particular their role in the regulation
      of mitochondrial transport machineries. This article is part of a Special Issue
      entitled Protein translocation across or insertion into membranes.

PMID- 20696128
TI  - Simulations of calcium channel block by trivalent cations: Gd(3+) competes with
      permeant ions for the selectivity filter.
AB  - Current through L-type calcium channels (Ca(V)1.2 or dihydropyridine receptor)
      can be blocked by micromolar concentrations of trivalent cations like the
      lanthanide gadolinium (Gd(3+)). It has been proposed that trivalent block is due
      to ions competing for a binding site in both the open and closed configuration,
      but possibly with different trivalent affinities. Here, we corroborate this
      general view of trivalent block by computing conductance of a model L-type
      calcium channel. The model qualitatively reproduces the Gd(3+) concentration
      dependence and the effect that substantially more Gd(3+) is required to produce
      similar block in the presence of Sr(2+) (compared to Ba(2+)) and even more in the
      presence of Ca(2+). Trivalent block is explained in this model by cations binding
      in the selectivity filter with the charge/space competition mechanism. This is
      the same mechanism that in the model channel governs other selectivity
      properties. Specifically, selectivity is determined by the combination of ions
      that most effectively screen the negative glutamates of the protein while finding
      space in the midst of the closely packed carboxylate groups of the glutamate
      residues.

PMID- 20696130
TI  - In vivo assay of human NK-dependent ADCC using NOD/SCID/gammac(null) (NOG) mice.
AB  - Monoclonal antibodies are essential to the success of molecularly targeted
      therapies. Recently, numerous therapeutic antibodies have been developed for
      various diseases, including cancer and autoimmune diseases. Experimental systems
      to effectively evaluate these candidate antibodies are urgently needed. One of
      the mechanisms used by antibodies to kill tumor cells is antibody-dependent
      cellular cytotoxicity (ADCC), in which natural killer cells (NK) are the main
      mediator. The capacity to induce ADCC has conventionally been assessed in the
      human-mouse xeno-graft model, in which human peripheral blood mononuclear cells
      (PBMC), containing NK cells along with antibodies, are administered to tumor
      bearing immunodeficient mice. However, contamination from other cellular
      populations often affects tumor growth, making it difficult to evaluate the
      antibody's effect. In this study, we established a new NK-dependent ADCC assay
      model using a supra-immunodeficient strain of mice, NOD/SCID/gammac(null) (NOG).
      Our model system simply consisted of three elements: isolated human NK cells, a
      Burkitt's lymphoma cell line (Daudi), and an anti-CD20 antibody (Rituximab). In
      this experimental setting, human NK cells from healthy donors retained their
      killing activity and suppressed the growth of Daudi cells in NOG mice when they
      were administered along with Rituximab. This system, therefore, is useful for
      evaluating the in vivo function of human NK cells.

PMID- 20696131
TI  - MyD88-dependent pathway accelerates the liver damage of Concanavalin A-induced
      hepatitis.
AB  - We have explored the pathological role of the MyD88 signaling pathway via Toll
      like receptors (TLRs) that mediate the recognition of pathogen-associated
      molecular patterns (PAMPs) in a murine model of autoimmune hepatitis induced by
      administering Concanavalin A (ConA). We first found that various TLRs and MyD88
      molecules were expressed in liver of Con A-treated and untreated wild-type (WT)
      mice including liver macrophages. Flowcytometric analysis revealed that liver
      CD11b(+)CD11c(-) and CD11b(+)CD11c(+) antigen-presenting cells express TLR2,
      although NK and NKT cells did not. When WT and MyD88(-/-) mice were intravenously
      administered with Con A, the severity of hepatitis was significantly lower in Con
      A-injected MyD88(-/-) mice than in WT mice in terms of the histopathology, the
      levels of serum transaminase and pro-inflammatory cytokines (TNF-alpha, IFN
      gamma, and IL-6), and upregulation of CD80/CD86 and TNF-alpha on/in liver
      macrophages. The results provide evidence of a possible contribution of the TLRs
      MyD88 signaling pathway in activating TLR-expressing liver macrophages in the
      autoimmune hepatitis model, and thus indicate that the strategy of blockade of
      pathological pathogens via the intestinal lumen may be feasible for the treatment
      of the disease.

PMID- 20696132
TI  - Circulating muscle-specific microRNA, miR-206, as a potential diagnostic marker
      for rhabdomyosarcoma.
AB  - Presently there is no serum biomarker of rhabdomyosarcoma (RMS). Several studies
      have shown that profiles of microRNA (miRNA) expression differ among tumor types.
      Here we evaluated the feasibility of using muscle-specific miRNAs (miR-1, -133a, 
      133b and -206) as biomarkers of RMS. Expression of muscle-specific miRNAs,
      especially miR-206, was significantly higher in RMS cell lines than in other
      tumor cell lines, as well as in RMS tumor specimens. Further, serum levels of
      muscle-specific miRNAs were significantly higher in patients with RMS tumors than
      in patients with non-RMS tumors. Normalized serum miR-206 expression level could
      be used to differentiate between RMS and non-RMS tumors, with sensitivity of 1.0
      and specificity of 0.913. These results raise the possibility of using
      circulating muscle-specific miRNAs, especially miR-206, as landmark biomarkers
      for RMS.

PMID- 20696133
TI  - Sulfuretin attenuates allergic airway inflammation in mice.
AB  - Sulfuretin is one of the main flavonoids produced by Rhus verniciflua, which is
      reported to inhibit the inflammatory response by suppressing the NF-kappaB
      pathway. Because NF-kappaB activation plays a pivotal role in the pathogenesis of
      allergic airway inflammation, we here examined the effect of sulfuretin on an
      ovalbumin-induced airway inflammation model in mice. We isolated sulfuretin from
      R. verniciflua. Sulfuretin was delivered intraperitoneally after the last
      ovalbumin challenge. Airway hyper-responsiveness, cytokines, mucin, and
      eosinophilic infiltration were analyzed in bronchoalveolar lavage fluid and lung
      tissue. A single administration of sulfuretin reduced airway inflammatory cell
      recruitment and peribronchiolar inflammation and suppressed the production of
      various cytokines in bronchoalveolar fluid. In addition, sulfuretin suppressed
      mucin production and prevented the development of airway hyper-responsiveness.
      The protective effect of sulfuretin was mediated by the inhibition of the NF
      kappaB signaling pathway. Our results suggest that sulfuretin may have
      therapeutic potential for the treatment of allergic airway inflammation.

PMID- 20696134
TI  - ATF3 negatively regulates adiponectin receptor 1 expression.
AB  - Adiponectin is an adipocyte-derived hormone that has antidiabetic and
      antiatherogenic effects through two membrane receptors, adiponectin receptor 1
      (AdipoR1) and adiponectin receptor 2 (AdipoR2). Although it has been reported
      that the expression of AdipoR1 and AdipoR2 is regulated under physiological and
      pathophysiological states, their regulation is largely unknown. Previously, we
      demonstrated that endoplasmic reticulum (ER) stress or obesity-inducible ATF3
      negatively regulates the expression of adiponectin and AdipoR2. Here, we
      investigated the regulation of another adiponectin receptor, AdipoR1 by ATF3, to
      determine if ATF3 may contribute to impairment of adiponectin signaling by
      repressing the expression of both adiponectin and adiponectin receptors. We found
      that treatment with thapsigargin, a stimulator of ATF3 expression as an inducer
      of ER stress, decreased AdipoR1 expression in insulin-sensitive cells (HepG2,
      C2C12) and insulin secreting cells (MIN6N8). Furthermore, overexpression of
      lentivirus carrying-ATF3 decreased AdipoR1 expression in those cells,
      demonstrating that ATF3 downregulates AdipoR1 expression. Next, we investigated
      the effects of ATF3 on human AdipoR1 promoter activity and identified an ATF3
      responsive region in the promoter. Both thapsigargin treatment and ATF3
      expression repressed AdipoR1 promoter activity. Transfection studies using mutant
      constructs containing 5'-deletions in the human AdipoR1 promoter revealed that
      putative ATF/CRE site is located between the -248 and -224, TGACGCGG. Chromatin
      immunoprecipitation assay demonstrated that ATF3 directly binds to human AdipoR1
      promoter spanning from -248 to -224. Finally, deletion of the putative ATF/CRE
      site abrogated ATF3-mediated transrepression of the AdipoR1 promoter.
      Importantly, ATF3 expression was increased in hyperglycemia or TNF-alpha-treated
      C2C12 cells in which AdipoR1 expression was decreased, suggesting that ATF3 may
      contribute to downregulation of AdipoR1 by hyperglycemia and TNF-alpha.
      Collectively, these results demonstrate that ATF3 negatively regulates human
      AdipoR1 expression via binding to an ATF3-responsive region in the promoter,
      which plays an important role in attenuation of adiponectin signaling and
      induction of insulin resistance.

PMID- 20696135
TI  - Novel protein interactors of urokinase-type plasminogen activator receptor.
AB  - The urokinase-type plasminogen activator receptor (uPAR) has been implicated in
      tumor growth and metastasis. The crystal structure of uPAR revealed that the
      external surface is largely free to interact with a number of proteins.
      Additionally, due to absence of an intracellular cytoplasmic protein domain, many
      of the biological functions of uPAR necessitate interactions with other proteins.
      Here, we used yeast two-hybrid screening of breast cancer cDNA library to
      identify hSpry1 and HAX1 proteins as putative candidate proteins that interact
      with uPAR bait constructs. Interaction between these two candidates and uPAR was
      confirmed by GST-pull down, co-immunoprecipitation assays and confocal
      microscopy. These novel interactions that have been identified may also provide
      further evidence that uPAR can interact with a number of other proteins which may
      influence a range of biological functions.

PMID- 20696136
TI  - Escherichia coli ghosts promote innate immune responses in human keratinocytes.
AB  - Bacterial ghosts (BGs) as non-living bacterial envelopes devoid of cytoplasmic
      content with preserved and intact inner and outer membrane structures of their
      living counterparts have been used to study the ability of their surface
      components for the induction of antimicrobial peptides and pro-inflammatory
      cytokines in human primary keratinocytes (KCs). Quantitative real-time PCR
      analysis revealed that incubation of KCs with BGs generated from wild-type
      Escherichia coli induced the mRNA expression of antimicrobial psoriasin (S100A7c)
      in a BGs particle concentration-dependent manner. Using immunoblot analysis we
      showed that BGs generated from the flagellin-deficient (DeltaFliC) E. coli strain
      NK9375 were as effective as its isogenic wild-type (wt) E. coli strain NK9373 to
      induce psoriasin expression when normalized to BG particles being taken up by
      KCs. However, results obtained from endocytic activity of KCs reflect that
      internalization of BGs is greatly dependent on the presence of flagellin on the
      surface of BGs. Moreover, BGs derived from wt E. coli NK9373 strongly induced the
      release of the pro-inflammatory cytokines IL-6 and IL-8, compared to DeltaFliC E.
      coli NK9375 BGs. Taken together, obtained data demonstrate that non-living BGs
      possessing all bacterial bio-adhesive surface properties in their original state
      while not posing any infectious threat have the capacity to induce the expression
      of innate immune modulators and that these responses are partially dependent on
      the presence of flagellin.

PMID- 20696137
TI  - Marine sponge-derived sipholane triterpenoids reverse P-glycoprotein (ABCB1)
      mediated multidrug resistance in cancer cells.
AB  - Previously, we reported sipholenol A, a sipholane triterpenoid from the Red Sea
      sponge Callyspongia siphonella, as a potent reversal of multidrug resistance
      (MDR) in cancer cells that overexpressed P-glycoprotein (P-gp). Through extensive
      screening of several related sipholane triterpenoids that have been isolated from
      the same sponge, we identified sipholenone E, sipholenol L and siphonellinol D as
      potent reversals of MDR in cancer cells. These compounds enhanced the
      cytotoxicity of several P-gp substrate anticancer drugs, including colchicine,
      vinblastine and paclitaxel, and significantly reversed the MDR-phenotype in P-gp
      overexpressing MDR cancer cells KB-C2 in a dose-dependent manner. Moreover, these
      three sipholanes had no effect on the response to cytotoxic agents in cells
      lacking P-gp expression or expressing MRP1 (ABCC1) or MRP7 (ABCC10) or breast
      cancer resistance protein (BCRP/ABCG2). All three sipholanes (IC(50) >50 MUM)
      were not toxic to all the cell lines that were used. [(3)H]-Paclitaxel
      accumulation and efflux studies demonstrated that all three triterpenoids time
      dependently increased the intracellular accumulation of [(3)H]-paclitaxel by
      directly inhibiting P-gp-mediated drug efflux. Sipholanes also inhibited calcein
      AM transport from P-gp-overexpressing cells. The Western blot analysis revealed
      that these three triterpenoids did not alter the expression of P-gp. However,
      they stimulated P-gp ATPase activity in a concentration-dependent manner and
      inhibited the photolabeling of this transporter with its transport substrate
      [(125)I]-iodoarylazidoprazosin. In silico molecular docking aided the virtual
      identification of ligand binding sites of these compounds. In conclusion,
      sipholane triterpenoids efficiently inhibit the function of P-gp through direct
      interactions and may represent potential reversal agents for the treatment of
      MDR.

PMID- 20696138
TI  - Melatonin: a pleiotropic molecule regulating inflammation.
AB  - Melatonin is a neurohormone produced by the pineal gland that regulates sleep and
      circadian functions. Melatonin also regulates inflammatory and immune processes
      acting as both an activator and inhibitor of these responses. Melatonin
      demonstrates endocrine, but also paracrine and autocrine effects in the leukocyte
      compartment: on one side, leukocytes respond to melatonin in a circadian fashion;
      on the other side, leukocytes are able to synthesize melatonin by themselves.
      With its endocrine and paracrine effects, melatonin differentially modulates pro
      inflammatory enzymes, controls production of inflammatory mediators such as
      cytokines and leukotrienes and regulates the lifespan of leukocytes by
      interfering with apoptotic processes. Moreover, its potent antioxidant ability
      allows scavenging of oxidative stress in the inflamed tissues. The interesting
      timing of pro- and anti-inflammatory effects, such as those affecting
      lipoxygenase activity, suggests that melatonin might promote early phases of
      inflammation on one hand and contribute to its attenuation on the other hand, in
      order to avoid complications of chronic inflammation. This review aims at giving
      a comprehensive overview of the various inflammatory pathways regulated by this
      pleiotropic hormone.

PMID- 20696140
TI  - N-methyl-citalopram: A quaternary selective serotonin reuptake inhibitor.
AB  - We describe the synthesis and the pharmacological characterization of a new
      quaternary selective serotonin reuptake inhibitor (SSRI) N-methyl-citalopram
      (NMC) with periphery restricted action due to its inability to cross the blood
      brain barrier. NMC recognized and blocked the human platelet serotonin
      transporter (SERT) with similar affinity to that of citalopram as was evident
      from competition binding studies with [(3)H]citalopram and uptake studies with
      [(3)H]5-HT. In contrast, the affinity of NMC to rat brain SERT was 10-fold lower
      than its parent compound citalopram. Similarly to citalopram, NMC did not inhibit
      dopamine and noradrenaline uptake in rat brain synaptosomes at 10(-7)M as well as
      [(3)H]ketanserin binding to rat brain membranes at 10(-5)M, demonstrating its
      SSRI profile. A comparison of radioactivity retained in perfused mice brain
      following in vivo intraperitoneal injections of tritium-labeled NMC or citalopram
      showed that unlike citalopram, NMC did not penetrate the brain. Taken together,
      our observations suggest that N-methyl-citalopram is a selective serotonin
      reuptake inhibitor that does not penetrate the mouse brain. Epidemiological
      studies have suggested that chronic use of SSRI drugs may confer a protective
      effect against myocardial infarction (MI) apparently reflecting reduced platelet
      aggregation secondary to reduced platelet serotonin levels. N-methyl-citalopram
      may therefore have a potential as a new anti-platelet drug that does not cross
      the blood brain barrier and is thus devoid of the adverse CNS effects of SSRI
      drugs.

PMID- 20696141
TI  - Identification of a kappa-opioid agonist as a potent and selective lead for drug
      development against human African trypanosomiasis.
AB  - A resazurin-based cell viability assay was developed for phenotypic screening of
      the LOPAC 1280 'library of pharmacologically active compounds' against
      bloodstream forms of Trypanosoma brucei in vitro identifying 33 compounds with
      EC(50) values <1 MUM. Counter-screening vs. normal diploid human fibroblasts
      (MRC5 cells) was used to rank these hits for selectivity, with the most potent
      (<70 nM) and selective (>700-fold) compounds being suramin and pentamidine. These
      are well-known antitrypanosomal drugs which demonstrate the robustness of the
      resazurin cell viability assay. The most selective novel inhibitor was (+)-trans
      (1R,2R)-U50,488 having an EC(50) value of 60 nM against T. brucei and 270-fold
      selectivity over human fibroblasts. Interestingly, (-)-U50,488, a known CNS
      active kappa-opioid receptor agonist and other structurally related compounds
      were >70-fold less active or inactive, as were several MU- and kappa-opioid
      antagonists. Although (+)-U50,488 was well tolerated by the oral route and
      displayed good pharmaceutical properties, including high brain penetration, the
      compound was not curative in the mouse model of infection. Nonetheless, the
      divergence of antinociceptive and antitrypanosomal activity represents a
      promising start point for further exploratory chemistry. Bioinformatic studies
      did not reveal any obvious candidate opioid receptors and the target of this
      cytostatic compound is unknown. Among the other potent, but less selective
      screening hits were compound classes with activity against protein kinases,
      topoisomerases, tubulin, as well as DNA and energy metabolism.

PMID- 20696139
TI  - Tocotrienols, the vitamin E of the 21st century: its potential against cancer and
      other chronic diseases.
AB  - Initially discovered in 1938 as a "fertility factor," vitamin E now refers to
      eight different isoforms that belong to two categories, four saturated analogues
      (alpha, beta, gamma, and delta) called tocopherols and four unsaturated analogues
      referred to as tocotrienols. While the tocopherols have been investigated
      extensively, little is known about the tocotrienols. Very limited studies suggest
      that both the molecular and therapeutic targets of the tocotrienols are distinct
      from those of the tocopherols. For instance, suppression of inflammatory
      transcription factor NF-kappaB, which is closely linked to tumorigenesis and
      inhibition of HMG-CoA reductase, mammalian DNA polymerases and certain protein
      tyrosine kinases, is unique to the tocotrienols. This review examines in detail
      the molecular targets of the tocotrienols and their roles in cancer, bone
      resorption, diabetes, and cardiovascular and neurological diseases at both
      preclinical and clinical levels. As disappointment with the therapeutic value of
      the tocopherols grows, the potential of these novel vitamin E analogues awaits
      further investigation.

PMID- 20696143
TI  - Resveratrol modulates angiogenesis through the GSK3beta/beta-catenin/TCF
      dependent pathway in human endothelial cells.
AB  - Vascular endothelial growth factor (VEGF) plays a critical role in angiogenesis
      due to its potent and specific ability to promote the proliferation and migration
      of endothelial cells. Resveratrol has been shown to have many health-benefiting
      effects, including the protection of cardiovascular system. In this study we
      examined the effect of resveratrol on angiogenesis in human umbilical vein
      endothelial cells (HUVECs). We observed that resveratrol was able to modulate the
      expression of VEGF and the formation of vascular network in a biphasic pattern.
      While resveratrol at low concentrations, from 1 to 10MUM, up-regulated the
      expression of VEGF and promoted angiogenesis, it had opposite effect at high
      concentrations (20MUM and higher). The biphasic effect of resveratrol on
      angiogenesis was confirmed by chick chorioallantoic membrane assay. Up-regulation
      of VEGF expression depended on the nuclear accumulation and transcriptional
      activity of beta-catenin. Correspondingly, GSK3beta, a negative regulator of beta
      catenin, turned into a less active state (phosphorylated at Ser9) in cells
      exposed to 5MUM of resveratrol, but became more active at 20MUM. We demonstrated
      that both Akt and ERK signaling pathways, which are known to be critical for
      angiogenesis, became activated in response to 5MUM of resveratrol and functioned
      to inactivate GSK3beta. Our findings may have implications in the management of
      cardiovascular diseases and other conditions such as cancer by the use of
      resveratrol.

PMID- 20696144
TI  - Stimulation of dorsal root afferents increases the excitability of ascending
      sensory axons in the isolated spinal cord of mature mice.
AB  - The phenomenon of windup has often been used to assess excitability increases of
      spinal neurons induced by repetitive stimulation of nociceptive afferents. Windup
      has been studied in individual spinal cord neurons and in spinal motor reflexes
      neither of which accurately reflect the forward transmission of nociceptive
      signals to the brain. In addition, most in vitro studies of spinal windup have
      been conducted on immature or juvenile animals and it is challenging to
      extrapolate these results to the adult spinal cord. In the present study, we have
      used an in vitro whole spinal cord preparation from functionally mature mice (up
      to 8 weeks old) to record windup activity in ascending axons in the mid-thoracic
      region evoked by electrical stimulation of a lumbar or sacral dorsal root. Windup
      responses were observed in axons in the ipsi- and contralateral dorsolateral
      funiculus (iDLF and cDLF) and in the contralateral ventrolateral funiculus
      (cVLF). No windup responses were evoked in postsynaptic axons of the ipsilateral
      dorsal columns (iDC) and no postsynaptic responses were elicited in the
      ipsilateral ventrolateral funiculus (iVLF) or contralateral dorsal columns (cDC).
      Between 40% and 45% of all axons in the DLF and cVLF that responded to a single
      dorsal root stimulus also showed windup. The NMDA receptor antagonist MK-801
      reversibly blocked such windup responses. These results illustrate that windup
      can be consistently recorded from ascending pathways in the mature spinal cord in
      vitro but also show that windup can only be elicited in a proportion of sensory
      axons projecting through some, but not all, ascending spinal cord pathways.

PMID- 20696142
TI  - Inflammation and survival pathways: chronic lymphocytic leukemia as a model
      system.
AB  - A primary response to inflammation is an increased survival of the target cell.
      Several pathways have been identified that promote maintenance of the cell. The
      principal mechanism for the extended survival is through induction of anti
      apoptotic Bcl-2 family proteins. Bcl-2 was the founding member of this family
      with five additional members, Bcl-X(L), Bcl-W, Bcl-B, Bfl-1, and Mcl-1,
      discovered mostly in hematological malignancies. Another mechanism that could add
      to cell survival is the Pim kinase pathway. This family of enzymes is associated
      with Myc-driven transcription, cell cycle regulation, degradation of pro
      apoptotic proteins, and protein translation. Chronic lymphocytic leukemia serves
      as an optimal model to understand the mechanism by which these two protein
      families provide survival advantage to cells. In addition, since this malignancy
      is known to be maintained by microenvironment milieu, this further adds advantage
      to investigate mechanisms by which these pro-survival proteins are induced in the
      presence of stromal support. Multiple mechanisms exists that result in increase
      in transcript and protein level of anti-apoptotic Bcl-2 family members. Following
      these inductions, post-translational modifications occur resulting in increased
      stability of pro-survival proteins, while Pim-mediated phosphorylation inhibits
      pro-apoptotic protein activity. Furthermore, there is a cross-talk between these
      two (Bcl-2 family proteins and Pim family proteins) pathways that co-operate with
      each other for CLL cell survival and maintenance. Vigorous efforts are being made
      to create small molecules that affect these proteins directly or indirectly.
      Several of these pharmacological inhibitors are in early clinical trials for
      patients with hematological malignancies.

PMID- 20696145
TI  - The anti-nociceptive effect and the possible mechanism of acupoint stimulation
      caused by chemical irritants in the bee venom pain model.
AB  - Many studies have demonstrated the anti-nociceptive and anti-inflammatory effects
      of injecting bee venom (BV) into the Zusanli (ZSL) acupoint in rats. The present
      study was designed to determine whether the injection of other chemical
      irritants, such as formalin and complete Freund's adjuvant (CFA), into the ZSL
      acupoint can produce anti-nociceptive and anti-inflammatory effects in the BV
      pain model and to determine the possible mechanisms underlying these effects.
      First, the effects of injecting BV, formalin, CFA, or saline into the ZSL
      acupoint on intraplantar BV-induced persistent spontaneous pain, mechanical
      hyperalgesia, and inflammatory swelling of the injected paw were observed. BV,
      formalin, CFA, and saline injection into the ZSL acupoint significantly inhibited
      intraplantar BV-induced persistent spontaneous nociception (PSN) and mechanical
      hyperalgesia but had no effect on intraplantar BV-induced inflammatory swelling.
      Next, the effects of pretreatment with naloxone (5mg/kg, ip) or injection of
      0.15% capsaicin into the ZSL acupoint on the anti-nociceptive effect of BV
      acupuncture (BVA) were observed. Pretreatment with naloxone had no effect on the
      BVA-induced anti-nociceptive effect, intraplantar BV-induced PSN, and mechanical
      hyperalgesia. Pretreatment with capsaicin produced partial blockage of the BVA
      induced anti-nociceptive effect on PSN, but it had no effect on BVA-induced anti
      nociception of mechanical hyperalgesia. These results suggest that (1) chemical
      irritant acupuncture produces the anti-nociceptive effect but not the anti
      inflammatory effect in the BV pain model, and (2) chemical irritant acupuncture
      induced analgesia is a common mechanism that is not specific to BV acupuncture.
      Our results also suggest that the BVA-induced anti-nociceptive mechanism is
      partially mediated by capsaicin-sensitive primary afferent fibers but not by
      endogenous mu opioid receptors in the BV pain model.

PMID- 20696146
TI  - LIM kinase mediates estrogen action on the actin depolymerization factor Cofilin.
AB  - The ovarian hormone estrogen increases the axospinous synapse density in the
      hippocampal CA1 region of young female rats but fails to do so in aged rats. This
      estrogen-mediated alteration of spine synapse structures suggests the coincident
      requirement for the structural reorganization of the underlying actin
      cytoskeleton network. Actin reorganization is known to require the deactivation
      of Cofilin, an actin depolymerization factor. Cofilin is deactivated by LIM
      kinase (LIMK), and LIMK activity is modulated by the phosphorylation of specific
      residues. We have previously demonstrated that estrogen is able to increase
      phosphorylated LIMK (pLIMK) immunoreactivity (IR) in the hippocampus in vivo and
      that this estrogen-stimulated pLIMK-IR is decreased in the aged brain. Because
      Cofilin phosphorylation allows for actin filament elongation and spine synapse
      growth, we sought to determine if estrogen acts through Cofilin and if such
      estrogen action requires the observed LIMK activity. Using both hippocampal
      neurons and the NG108-15 neuroblastoma cell line, we demonstrate here that
      estrogen stimulates the phosphorylation of Cofilin in vitro. Furthermore, this
      estrogen action on Cofilin requires LIMK. Lastly, while initiating the
      phosphorylation of LIMK and Cofilin, estrogen can also stimulate the formation of
      filopodial extensions, an early step in the formation of nascent spines,
      demonstrating that estrogen can alter the actin-dependent neuronal morphology.
      This linkage of estrogen communication to Cofilin via LIMK provides the
      functionality to the age-sensitive pLIMK-IR that we have observed in vivo.

PMID- 20696147
TI  - Central monoamine levels differ between rat strains used in studies of depressive
      behavior.
AB  - Previous studies have shown that the Wistar-Kyoto (WKY) rat strain may be a
      genetic model of depression when their behaviors are compared to Sprague-Dawley
      (SD) or Wistar (WIS) rats. Significant differences in dopamine (DA), serotonin (5
      HT), and norepinephrine (NE) transporter site densities have been reported when
      comparing WKY to both SD and WIS rats. Susceptibility of WKY rats to anxiety and
      depressive behavior may be related to underlying differences in monoamine levels
      in various regions of the brain. Levels of monoamines (DA, 5-HT and NE) and their
      metabolites were measured in monoaminergic cell body, cortical and limbic brain
      regions using HPLC with electrochemical detection and compared between WKY, WIS
      and SD rats. In regions where strain differences in monoamine levels were
      observed (the basolateral amygdala, subregions of the hippocampus and the nucleus
      accumbens shell), WKY rats consistently had lower levels than SD rats. Similarly,
      WKY rats had lower monoamine levels compared to WIS, although these differences
      were observed in a more restricted number of brain regions. Interestingly, WIS
      rats showed reduced levels of the 5-HT metabolite 5-hydroxyindoleacetic acid (5
      HIAA) in several regions including the prefrontal cortex, subregions of the
      hippocampus and subregions of the hypothalamus, suggesting decreased 5-HT
      turnover when compared to both WKY and SD rats. Overall, these results imply that
      decreased monoamine levels, combined with alterations in transporter sites, may
      be related to the predisposition of WKY rats towards depressive behavior.

PMID- 20696148
TI  - Systemic administration of lipopolysaccharide induces molecular and morphological
      alterations in the hippocampus.
AB  - A systemic inflammatory reaction may have detrimental effects on the organism,
      including the central nervous system. Previous studies have indicated that
      lipopolysaccharide (LPS)-evoked systemic inflammation induces pathological
      alterations in the mouse midbrain, especially in the substantia nigra. The aim of
      the present study was to investigate whether the hippocampus is also affected
      after an intraperitoneal (i.p.) injection of LPS. We focussed on the dynamics of
      proinflammatory gene expression and the processes leading to neuronal cell death.
      A systemic inflammatory response in C57BL/6 mice was induced by an i.p. injection
      of LPS (1mg/kg b.w.). The genetic, biochemical and morphological alterations were
      analysed up to 96h after LPS administration using quantitative PCR,
      immunochemical, immunocytochemical and electron microscopic methods. Real-time
      PCR analysis indicated an altered expression of several genes, mainly responsible
      for arachidonic acid release and metabolism, in the hippocampus 96h after the
      systemic administration of LPS. Three hours after LPS treatment, the level of
      mRNA for iNOS, COX-2 and TNFalpha was increased; then, after 6-24h, it rose for
      TLR4 and cPLA2. The expression of 5-LOX and 12-LOX was increased at 12-24 and 24
      48h after LPS injection, respectively. Our data demonstrate for the first time
      the sequential activation of the expression of several pro-inflammatory genes
      responsible for the maintenance of the inflammatory response. Moreover, the
      electron microscopy studies presented the stimulation of apoptosis-inducing
      factor (AIF)-mediated death signalling and cathepsin B-related autophagy or
      necrosis. These biochemical and morphological alterations in the hippocampus,
      which were induced by systemic inflammation, may be responsible for the
      impairment of cognition function observed previously.

PMID- 20696149
TI  - GABA-A and GABA-B receptors mediate feeding elicited by the GABA-B agonist
      baclofen in the ventral tegmental area and nucleus accumbens shell in rats:
      reciprocal and regional interactions.
AB  - Food intake is significantly increased following administration of GABA-B and
      GABA-A agonists into the nucleus accumbens (NAC) shell and ventral tegmental area
      (VTA) with receptor-selective antagonist pretreatment capable of blocking these
      responses within sites. Regional interactions in feeding studies have been
      evaluated by administering an antagonist in one site of interest prior to
      administration of the feeding-active agonist in a second site of interest and
      have identified important relationships, particularly for opioid-opioid
      interactions. To evaluate whether regional and reciprocal VTA and NAC shell
      interactions occur for GABA-mediated feeding, the present study examined whether
      feeding elicited by the GABA-B agonist, baclofen, microinjected into the NAC
      shell was dose-dependently blocked by pretreatment with either the GABA-B
      antagonist, saclofen, or the GABA-A antagonist, bicuculline, into the VTA, and
      then whether VTA baclofen-induced feeding was dose-dependently blocked by NAC
      shell pretreatment of either saclofen or bicuculline in rats. Rats were
      stereotaxically implanted with bilateral pairs of cannulae aimed at the VTA and
      NAC shell and were assessed for food intake following vehicle and baclofen (200
      ng) in each site. Baclofen produced similar magnitudes of increased food intake
      following VTA and NAC shell treatment. Baclofen administration in the VTA and NAC
      shell was preceded 20 min earlier with administration of bicuculline (0, 7.5, 75,
      150, 300 ng) or saclofen (0, 0.5, 1.5, 3, 5 MUg) into the other site with intake
      measured 1, 2 and 4h after agonist treatment. VTA saclofen dose-dependently and
      significantly blocked feeding elicited by NAC shell baclofen. Correspondingly,
      NAC shell saclofen dose-dependently and significantly blocked feeding elicited by
      VTA baclofen, indicating a robust and bidirectional GABA-B/GABA-B receptor
      interaction between sites. Whereas VTA bicuculline significantly blocked the
      increased feeding elicited by NAC shell baclofen, NAC shell bicuculline reduced
      but did not block feeding elicited by VTA baclofen, indicating a unidirectional
      interaction GABA-B/GABA-A receptor interaction between sites. Unlike within-site
      receptor specificity governing the ability of GABA agonist mediation of food
      intake, the present study demonstrates that GABA, like opioids, employs a
      distributed brain network in mediating its ingestive effects, and that under
      certain circumstances, uses multiple receptor subtypes to underlie its regional
      effects.

PMID- 20696150
TI  - Molecular and biochemical characterization of human galactokinase and its small
      molecule inhibitors.
AB  - Human galactokinase (GALK) is the first enzyme in the Leloir pathway, converting
      alpha-d-galactose into galactose-1-phosphate (Gal-1-P). Recently, there is
      increasing interest in targeting GALK as a novel therapy to ameliorate the
      disease manifestations in patients with Classic Galactosemia as it would, in
      combination with (ga-)lactose restriction reduce accumulation of Gal-1-P, a
      cytotoxic agent. Previously, we identified 34 small molecule compounds that
      inhibited GALK in vitro using experimental high-throughput screening. In order to
      isolate useful lead compounds, we characterized these hits with regards to their
      kinase selectivity profiles, potency and capability to reduce Gal-1-P
      accumulation in patient cell lines, and their modes of action. We found that the
      majority of these compounds had IC(50)s ranging from 0.7MUM to 33.3MUM. When
      tested against other members of the GHMP kinase family, three compounds (1, 4,
      and 24) selectively inhibited GALK with high potency. Through alignment of GALK
      and mevalonate kinase (MVK) crystal structures, we identified that eight amino
      acid residues and an L1 loop were different within the ATP-binding pockets of
      these two closely related kinases. By site-directed mutagenesis experiments, we
      identified one amino acid residue required for the inhibitory function of two of
      the three selective compounds. Based on these results, we generated binding
      models of these two compounds using a high-precision docking program. Compounds 4
      and 24 inhibited GALK in a mixed model, while compound 1 exhibited parabolic
      competitive inhibition. Most importantly, using cells from galactosemic patients
      we found that selected compounds lowered Gal-1-P concentrations.

PMID- 20696151
TI  - Antihyperlipidemic effect of chlorogenic acid and tetrahydrocurcumin in rats
      subjected to diabetogenic agents.
AB  - Diabetes mellitus is associated with dyslipidemia, which is a significant risk
      factor for cardiovascular complications. The present study was carried out to
      evaluate the effects of tetrahydrocurcumin (THC) and chlorogenic acid (CGA) alone
      and in combination on alterations in lipids, lipoproteins and enzymes involved in
      lipid metabolism in streptozotocin (STZ)-nicotinamide (NA)-induced type 2
      diabetic rats. A significant (p<0.05) increase in the concentrations of plasma
      and tissue (liver and kidney) lipids (cholesterol, triglycerides (TGs), free
      fatty acids (FFAs) and phospholipids (PLs)) and low density and very low-density
      lipoproteins (LDL and VLDL), and a decrease in the concentration of high-density
      lipoproteins (HDL) were noticed in STZ administered diabetic rats. In addition,
      the activity of 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase
      increased significantly (p<0.05) in the liver and kidney whereas the activities
      of lipoprotein lipase (LPL) and lecithin cholesterol acyl transferase (LCAT) were
      decreased significantly (p<0.05) in the plasma of diabetic rats. Combined
      administration of CGA (5mg/kg b.w.) and THC (80mg/kg b.w.) for 45 days remarkably
      reduced the STZ-induced changes in lipids, lipoproteins and lipid metabolising
      enzymes when compared to the effects of CGA or THC alone in diabetic rats. These
      results indicate that combination of THC and CGA can potentially ameliorate lipid
      abnormalities in experimental type 2 diabetes.

PMID- 20696152
TI  - Evaluation of mild hyperhomocysteinemia during the development of atherosclerosis
      in apolipoprotein E-deficient and normal mice.
AB  - We focused on the effect of mild hyperhomocysteinemia (HHcy) on the development
      of atherosclerosis, using apolipoprotein E-deficient (apoE(-/-)) and normal mice.
      Mice received diets enriched in methionine with low or high levels of folate,
      B(12) and B(6) (diets B and C, respectively), and diet only with low levels of
      folate, B(12) and B(6) (diets D), to induce mild HHcy. Normal mice fed on diets
      B, C and D presented mild HHcy, but they did not develop atherosclerotic lesions
      after 24 weeks of diet. In addition, increased endoplasmic reticulum stress was
      present in normal mice fed on diet B, compared to others groups. ApoE(-/-) mice
      fed on diet B for 20 weeks presented the greatest atherosclerotic lesion area at
      the aortic sinus than other groups. These results suggest that the methionine may
      have a toxic effect on endothelium, and the B-vitamins addition on diet may have
      a protective effect in the long term, despite the increase on homocysteine
      levels. Mild HHcy accelerated the development of atherosclerosis in apoE(-/-)
      mice, and supplementation with B-vitamins is important for prevention of vascular
      disease, principally in the long term.

PMID- 20696153
TI  - Six family genes control the proliferation and differentiation of muscle
      satellite cells.
AB  - Muscle satellite cells are essential for muscle growth and regeneration and their
      morphology, behavior and gene expression have been extensively studied. However,
      the mechanisms involved in their proliferation and differentiation remain
      elusive. Six1 and Six4 proteins were expressed in the nuclei of myofibers of
      adult mice and the numbers of myoblasts positive for Six1 and Six4 increased
      during regeneration of skeletal muscles. Six1 and Six4 were expressed in
      quiescent, activated and differentiated muscle satellite cells isolated from
      adult skeletal muscle. Overexpression of Six4 and Six5 repressed the
      proliferation and differentiation of satellite cells. Conversely, knockdown of
      Six5 resulted in augmented proliferation, and that of Six4 inhibited
      differentiation. Muscle satellite cells isolated from Six4(+/-)Six5(-/-) mice
      proliferated to higher cell density though their differentiation was not altered.
      Meanwhile, overproduction of Six1 repressed proliferation and promoted
      differentiation of satellite cells. In addition, Six4 and Six5 repressed, while
      Six1 activated myogenin expression, suggesting that the differential regulation
      of myogenin expression is responsible for the differential effects of Six genes.
      The results indicated the involvement of Six genes in the behavior of satellite
      cells and identified Six genes as potential target for manipulation of
      proliferation and differentiation of muscle satellite cells for therapeutic
      applications.

PMID- 20696154
TI  - Safety and immunogenicity of the malaria vaccine candidate GMZ2 in malaria
      exposed, adult individuals from Lambarene, Gabon.
AB  - Malaria is still one of the major public health threats in sub-Saharan Africa. An
      effective vaccine could be a sustainable control measure that can be integrated
      into existing health infrastructures. The malaria vaccine candidate GMZ2 is a
      recombinant fusion protein of conserved parts of Plasmodium falciparum Glutamate
      Rich Protein and Merozoite Surface Protein 3 adjuvanted with aluminium hydroxide.
      GMZ2 is immunogenic and well tolerated in malaria-naive adults from Germany. To
      assess safety and immunogenicity in malaria-exposed individuals, 40 adults from
      Lambarene, Gabon were randomly assigned to receive either 100 MUg GMZ2 or a
      rabies control vaccine three times in monthly intervals. Both vaccines were well
      tolerated. One month after a full course of vaccination, GMZ2-vaccinated
      individuals had 1.4-fold (95% confidence interval: [1.1, 1.7]) higher baseline
      corrected anti-GMZ2 antibody levels and more GMZ2-specific memory B-cells
      compared to the rabies group (p=0.039), despite a high prevalence of GMZ2
      specific immune reactivity due to previous intense exposure to P. falciparum.

PMID- 20696155
TI  - Loss of peripapillary sparing in non-group I Stargardt disease.
AB  - The aim of this study was to assess peripapillary sparing in patients with non
      group I Stargardt disease. We suggest this as a useful clinical sign for
      formulating disease severity. Patients with a diagnosis of Stargardt disease were
      grouped by electroretinogram (ERG). Fundus autofluorescence was used to assess
      the peripapillary area for involvement in the Stargardt disease process. From a
      cohort of 32 patients (64 eyes), 17 patients (33 eyes) demonstrated loss of
      peripapillary sparing. One of 15 patients in Group I, six of 7 patients in group
      II and 9 of 10 patients in group III demonstrated peripapillary atrophy. One
      patient in group II had peripapillary flecks. All patients had at least one
      mutation detected in the ABCA4 gene. Both mutations were detected in 21 patients.
      Patients in groups II and III had the earliest ages of onset and the poorest
      visual acuities. Two novel disease causing mutation in the ABCA4 gene were
      detected. Our data supports the observation that peripapillary sparing is not
      universal finding for Stargardt disease and peripapillary atrophy is a useful
      clinical sign for identifying patients with Stargardt disease who fall into the
      more severe ERG groups, i.e. groups II and III. The presence of atrophy suggests
      a continuum of disease between groups II and III. Loss of peripapillary sparing
      is likely associated with the more deleterious mutations of the ABCA4 gene.

PMID- 20696156
TI  - Effect of bestrophin-1 on L-type Ca2+ channel activity depends on the Ca2+
      channel beta-subunit.
AB  - Best's vitelliforme macular degeneration is an inherited retinal degeneration
      associated with a reduction of the light-peak in the patient's electro-oculogram.
      Bestrophin-1, the product of the disease-promoting/forming gene can function as
      regulator of voltage-dependent L-type Ca(2+) channels in the retinal pigment
      epithelium (RPE). Since mice deficient for either beta4-subunits or Ca(V)1.3
      subunits show reduced light-peaks, the regulatory function of bestrophin-1 on
      heterologously expressed Ca(2+) channels composed of the pore-forming Ca(V)1.3
      and the auxiliary beta4-subunit was analyzed. Precipitation of beta4-subunits led
      to co-precipitation with bestrophin-1 and subsequent analysis of subcellular
      localization showed co-localization of bestrophin-1, Ca(V)1.3 and beta4-subunit
      in the cell membrane. Ca(V)1.3 currents in the presence of beta4-subunits and
      bestrophin-1 showed accelerated time-dependent activation and decreased current
      density compared to currents measured in the absence of bestrophin-1. In the
      presence of the beta3-subunit, which is not expressed in the RPE bestrophin-1 did
      not modulate Ca(V)1.3 activity. Deletion of a cluster of proline-rich motifs in
      the C-terminus of bestrophin-1 reduced its co-immuno precipitation with the beta4
      subunit and strongly reduced the Ca(V)1.3 activity. Cells co-expressing
      bestrophin-1 lacking the proline-rich motifs and Ca(V)1.3 subunits showed less
      efficient trafficking of bestrophin-1 into the cell membrane. In summary, we
      conclude that bestrophin-1 modulates L-type channels of the RPE via proline-rich
      motif-dependent interaction with beta4-subunits. A disturbed interaction reduces
      the currents of the Ca(V)1.3 subunits. This mechanism could open new ways to
      understand changes in the patient's electro-oculogram and functional alterations
      of the RPE leading to retinal degeneration.

PMID- 20696158
TI  - Focus on molecules: melanopsin.

PMID- 20696157
TI  - The inhibitor of phagocytosis, O-phospho-L-serine, suppresses Muller glia
      proliferation and cone cell regeneration in the light-damaged zebrafish retina.
AB  - The damaged zebrafish retina replaces lost neurons through a regenerative
      response that initiates with the asymmetric cell division of Muller glia to
      produce neuronal progenitor cells that proliferate and migrate to the damaged
      retinal layer, where they differentiate into the lost neuronal cell types.
      Because Muller glia are known to phagocytose apoptotic retinal cells during
      development, we tested if Muller glia engulfed apoptotic rod cell bodies in light
      damaged retinas. After 24h of constant intense light, damaged retinas revealed
      both a strong nuclear TUNEL signal in photoreceptors and a weak cytoplasmic TUNEL
      signal in Muller glia, although Muller glial apoptosis is not observed in the
      light-damaged retina. Light damage of a rod-specific transgenic reporter line,
      Tg(XlRho:EGFP)(fl1), resulted in some Muller glia containing both TUNEL signal
      and EGFP, which indicated that this subset of Muller glia engulfed apoptotic
      photoreceptor cell bodies. To determine if phagocytosis induced the Muller glial
      proliferative response in the light-damaged retina, we utilized O-phospho-l
      serine (L-SOP), a molecule that mimics the phosphatidylserine head group and
      partially blocks microglial phagocytosis of apoptotic cells. Intravitreal
      injection of L-SOP immediately prior to beginning constant intense light
      treatment: i) did not significantly reduce light-induced photoreceptor cell
      death, ii) significantly reduced the number of PCNA-positive Muller glia, and
      iii) significantly reduced the number of cone photoreceptors in the regenerated
      retina relative to control retinas. Because L-SOP is also a specific group III
      metabotropic glutamate receptor (mGluR) agonist, we also tested if the more
      potent specific group III agonist, L-2-amino-4-phosphonobutyrate (L-AP4), the
      specific group III antagonist (RS)-alpha-Methylserine-O-phosphate (MSOP) or the
      specific group I antagonist, L-2-amino-3-phophonopropanoic acid (L-AP3) affected
      Muller glial proliferation. We found no changes with any of these factors
      compared to control retinas, revealing that metabotropic glutamate receptors were
      not necessary in the Muller glia proliferative response. Furthermore, ascl1a and
      stat3 expression were unaffected in either the L-SOP or MSOP-injected retinas
      relative to controls, suggesting L-SOP disrupts Muller glia proliferation
      subsequent to or in parallel with ascl1a and stat3 activation. This implies that
      at least one signaling mechanism, in addition to the process disrupted by L-SOP,
      is required to activate Muller glia proliferation in the light-damaged retina.

PMID- 20696159
TI  - Superior calcium homeostasis of extraocular muscles.
AB  - Extraocular muscles (EOMs) are a unique group of skeletal muscles with unusual
      physiological properties such as being able to undergo rapid twitch contractions
      over extended periods and escape damage in the presence of excess intracellular
      calcium (Ca(2+)) in Duchenne's muscular dystrophy (DMD). Enhanced Ca(2+)
      buffering has been proposed as a contributory mechanism to explain these
      properties; however, the mechanisms are not well understood. We investigated
      mechanisms modulating Ca(2+) levels in EOM and tibialis anterior (TA) limb
      muscles. Using Fura-2 based ratiometric Ca(2+) imaging of primary myotubes we
      found that EOM myotubes reduced elevated Ca(2+) ~2-fold faster than TA myotubes,
      demonstrating more efficient Ca(2+) buffering. Quantitative PCR (qPCR) and
      western blotting revealed higher expression of key components of the Ca(2+)
      regulation system in EOM, such as the cardiac/slow isoforms sarcoplasmic Ca(2+)
      ATPase 2 (Serca2) and calsequestrin 2 (Casq2). Interestingly EOM expressed
      monomeric rather than multimeric forms of phospholamban (Pln), which was
      phosphorylated at threonine 17 (Thr17) but not at the serine 16 (Ser16) residue.
      EOM Pln remained monomeric and unphosphorylated at Ser16 despite protein kinase A
      (PKA) treatment, suggesting differential signalling and modulation cascades
      involving Pln-mediated Ca(2+) regulation in EOM. Increased expression of
      Ca(2+)/SR mRNA, proteins, differential post-translational modification of Pln and
      superior Ca(2+) buffering is consistent with the improved ability of EOM to
      handle elevated intracellular Ca(2+) levels. These characteristics provide
      mechanistic insight for the potential role of superior Ca(2+) buffering in the
      unusual physiology of EOM and their sparing in DMD.

PMID- 20696161
TI  - Regulation of peripheral myelination by Src-like kinases.
AB  - Fyn, a nonreceptor Src-like tyrosine kinase (SLK), plays an important role in
      oligodendrocyte differentiation and myelination in the brain. However, its role
      in myelination of peripheral nerves remains undefined. Here we report that
      selective inhibitors of SLKs (PP2 and SU6656) caused a dose-dependent decrease in
      the accumulation of several myelin proteins, including myelin basic protein
      (MBP), protein zero (P0) and myelin-associated glycoprotein (MAG) in rat Schwann
      cell-dorsal root ganglion neuron (SC-DRGN) co-cultures. Interestingly, SLK
      inhibition was insufficient to completely abrogate myelin synthesis, as removal
      of PP2 after several days of treatment permitted a partial recovery of myelin
      proteins expression. Furthermore, fewer and shorter myelinated segments formed in
      the continuous presence of PP2, although the myelin formed was normally
      compacted. PP2 also decreased the number of SCs expressing Krox-20, a master
      regulatory transcription factor expressed by myelinating SCs, by 50%. These
      results were corroborated by selective knockdown of Fyn and Lyn kinases using
      siRNA. Extracellular matrix is important to SC differentiation and peripheral
      myelination. Using phospho-specific antibodies, we showed that addition of
      extracellular matrix extracts to SC-DRGN co-cultures resulted in the activation
      of ERK, Akt and p38 MAPK, three protein kinases involved in SC proliferation,
      differentiation and peripheral myelination. PP2 blocked the phosphorylation of
      all three kinases. Our results support a role for SLKs in the initiation of
      peripheral myelination via the activation of p38, Akt and ERK, which regulate
      Krox-20 expression and peripheral myelination.

PMID- 20696160
TI  - Tuberoinfundibular peptide of 39 residues (TIP39) signaling modulates acute and
      tonic nociception.
AB  - Tuberoinfundibular peptide of 39 residues (TIP39) synthesizing neurons at the
      caudal border of the thalamus and in the lateral pons project to areas rich in
      its receptor, the parathyroid hormone 2 receptor (PTH2R). These areas include
      many involved in processing nociceptive information. Here we examined the
      potential role of TIP39 signaling in nociception using a PTH2R antagonist (HYWH)
      and mice with deletion of TIP39's coding sequence or PTH2R null mutation.
      Intracerebroventricular (icv) infusion of HYWH significantly inhibited
      nociceptive responses in tail-flick and hot-plate tests and attenuated the
      nociceptive response to hindpaw formalin injection. TIP39-KO and PTH2R-KO had
      increased response latency in the 55 degrees C hot-plate test and reduced
      responses in the hindpaw formalin test. The tail-flick test was not affected in
      either KO line. Thermal hypoalgesia in KO mice was dose-dependently reversed by
      systemic administration of the cannabinoid receptor 1 (CB1) antagonist
      rimonabant, which did not affect nociception in wild-type (WT). Systemic
      administration of the cannabinoid agonist CP 55,940 did not affect nociception in
      KO mice at a dose effective in WT. WT mice administered HYWH icv, and both KOs,
      had significantly increased stress-induced analgesia (SIA). Rimonabant blocked
      the increased SIA in TIP39-KO, PTH2R-KO or after HYWH infusion. CB1 and FAAH mRNA
      were decreased and increased, respectively, in the basolateral amygdala of TIP39
      KO mice. These data suggest that TIP39 signaling modulates nociception, very
      likely by inhibiting endocannabinoid circuitry at a supraspinal level. We infer a
      new central mechanism for endocannabinoid regulation, via TIP39 acting on the
      PTH2R in discrete brain regions.

PMID- 20696162
TI  - Reconstitution of the olfactory epithelium following injury in apoE-deficient
      mice.
AB  - ApoE, a protein component of lipoproteins, is extensively expressed in the
      primary olfactory pathway. Because apoE has been shown to play a vital role in
      nerve repair and remodeling, we hypothesized that apoE expression will increase
      in the injured olfactory epithelium (OE), and that apoE deficiency in apoE
      knockout (KO) mice will lead to delayed/incomplete reconstitution of the OE
      following injury. To directly test this hypothesis, we compared OE regeneration
      in wild-type (WT) and KO mice following injury induced by intranasal irrigation
      of Triton X-100. OE was collected at 0, 3, 7, 21, 42, and 56 days post lesion.
      The amount and distribution of apoE in the regenerating OE was measured by
      immunoblotting and immunohistochemistry. Rate of OE reconstitution in WT and KO
      mice was assessed by using three independent measures: (1) OE thickness was
      measured in cresyl-violet stained sections, (2) basal cell proliferation was
      determined by using bromodeoxyuridine (BrdU) staining, and (3) differentiation
      and maturation of olfactory sensory neurons were measured by immunoblotting and
      immunohistochemical analysis of growth associated protein (GAP) 43 and olfactory
      marker protein (OMP). The results revealed that apoE expression in the OE is
      highly regulated during the entire course of OE reconstitution post injury, and
      that apoE deficiency in apoE KO mice leads to delayed recovery of mature OMP(+)
      cells in the reconstituting OE. The data suggest that apoE production increases
      in the injured OE to facilitate maturation of olfactory sensory neurons.

PMID- 20696163
TI  - The effect of mild post-stroke exercise on reactive neurogenesis and recovery of
      somatosensation in aged rats.
AB  - Exercise impacts the cellular response and behavioral recovery following stroke,
      but has not been widely investigated in aged animals. We tested the hypothesis
      that gentle post-stroke exercise could enhance recovery of somatosensory function
      and influence survival and phenotype of newly generated cells in the peri-infarct
      region after focal cortical ischemia in aged rats. Focal stroke was induced in
      the forelimb area of the sensorimotor cortex in 18-month old male rats using the
      vasoconstrictor endothelin-1. Beginning 1 week after stroke or sham surgery, half
      of the animals walked 100-300 m daily, 5 days per week. Bromodeoxyuridine (BrdU)
      was administered on days 6-8 post-stroke in order to label proliferating cells,
      the survival and phenotype of which were examined 4 weeks later using confocal
      microscopy. Post-stroke exercise enhanced recovery of somatosensory function as
      measured by the Adhesive Removal Test. Stroke, but not exercise, increased the
      number of BrdU+ cells in the peri-infarct region. In aged rats, mild post-stroke
      exercise enhances recovery of somatosensation, but has little effect on survival
      and phenotype of cells born in response to ischemia. Our results underscore the
      need for further study of clinically relevant post-stroke exercise regimens.

PMID- 20696164
TI  - POSH2 is a RING finger E3 ligase with Rac1 binding activity through a partial
      CRIB domain.
AB  - The Plenty of SH3 domains protein (POSH) is an E3 ligase and a scaffold in the
      JNK mediated apoptosis, linking Rac1 to downstream components. We here describe
      POSH2 which was identified from a p21-activated kinase 2 (PAK2) interactor
      screen. POSH2 is highly homologous with other members of the POSH family; it
      contains four Src homology 3 (SH3) domains and a RING finger domain which confers
      E3 ligase activity to the protein. In addition POSH2 contains an N-terminal
      extension which is conserved among its mammalian counterparts. POSH2 interacts
      with GTP-loaded Rac1. We have mapped this interaction to a previously
      unrecognized partial Cdc42/Rac1-interactive binding domain.

PMID- 20696165
TI  - Tankyrase-1 assembly to large protein complexes blocks its telomeric function.
AB  - Tankyrase-1 poly(ADP-ribosyl)ates the telomere-binding protein TRF1. This post
      translational modification dissociates TRF1 from telomeres, enhancing telomerase
      mediated telomere elongation. Tankyrase-1 multimerizes via its sterile alpha
      motif domain, but its functional implication remains elusive. Here, we found that
      excessive amounts of tankyrase-1 form punctate nuclear foci. This focus formation
      depends on both homophilic multimerization and heterophilic protein-protein
      interaction. These foci are functionally dormant because they do not efficiently
      release TRF1 from telomeres. Consistently, hyper-overexpression of tankyrase-1
      attenuates its ability to elongate telomeres. These observations suggest that
      tankyrase-1 assembly to large protein complexes masks its telomeric function.

PMID- 20696166
TI  - Mast cell signaling: the role of protein tyrosine kinase Syk, its activation and
      screening methods for new pathway participants.
AB  - The aggregation by antigen of the IgE bound to its high affinity receptor on mast
      cells initiates a complex series of biochemical events that result in the release
      of inflammatory mediators. The essential role of the protein tyrosine kinase Syk
      has been appreciated for some time, and newer results have defined the mechanism
      of its activation. The use of siRNA has defined the relative contribution of Syk,
      Fyn and Gab2 to signaling and has made possible a screening study to identify
      previously unrecognized molecules that are involved in these pathways.

PMID- 20696167
TI  - Structural identity of telomeric complexes.
AB  - A major issue in telomere research is to understand how the integrity of
      chromosome ends is controlled. Although several nucleoprotein complexes have been
      described at the telomeres of different organisms, it is still unclear how they
      confer a structural identity to chromosome ends in order to mask them from DNA
      repair and to ensure their proper replication. In this review, we describe how
      telomeric nucleoprotein complexes are structured, comparing different organisms
      and trying to link these structures to telomere biology. It emerges that
      telomeres are formed by a complex and specific network of interactions between
      DNA, RNA and proteins. The fact that these interactions and associated activities
      are reinforcing each other might help to guaranty the robustness of telomeric
      functions across the cell cycle and in the event of cellular perturbations. We
      propose that telomeric nucleoprotein complexes orient cell fate through dynamic
      transitions in their structures and their organization.

PMID- 20696168
TI  - Quantitative meta-analysis identifies brain regions activated during rectal
      distension in irritable bowel syndrome.
AB  - BACKGROUND AND AIMS: The responsiveness of the central nervous system is altered
      in patients with irritable bowel syndrome (IBS). However, because of variations
      in experimental paradigms, analytic techniques, and reporting practices, little
      consensus exists on brain responses to visceral stimulation. We aimed to identify
      brain regions consistently activated by supraliminal rectal stimulation in IBS
      patients and healthy subjects (controls) by performing a quantitative meta
      analysis of published studies. METHODS: Significant foci from within-group
      statistical parametric maps were extracted from published neuroimaging studies
      that employed rectal distension. Voxel-based activation likelihood estimation was
      applied, pooling the results and comparing them across groups. RESULTS: Across
      studies, there was consistent activation in regions associated with visceral
      afferent processing (ie, thalamus, insula, anterior midcingulate) among IBS
      patients and controls, but considerable differences in the extent and specific
      location of foci. IBS patients differed from controls in that there were more
      consistent activations in regions associated with emotional arousal (pregenual
      anterior cingulate cortex, amygdala) and activation of a midbrain cluster, a
      region playing a role in endogenous pain modulation. Controls showed more
      consistent activation of the medial and lateral prefrontal cortex. CONCLUSIONS:
      Patients with IBS have greater engagement of regions associated with emotional
      arousal and endogenous pain modulation, but similar activation of regions
      involved in processing of visceral afferent information. Controls have greater
      engagement of cognitive modulatory regions. These results support a role for
      central nervous system dysregulation in IBS. These findings provide specific
      targets for guiding development of future neuroimaging protocols to more clearly
      define altered brain-gut interactions in IBS.

PMID- 20696169
TI  - Pharmacokinetic immunoassay methods in the presence of soluble target.
AB  - Soluble targets represent a special challenge when employing ligand binding
      assays to support pharmacokinetic analysis of monoclonal therapeutics. Target
      engaged antibody is not available for binding in immunoassays employing anti
      idiotype-specific antibodies or target for capture. We investigated several
      formats of total antibody assays that show reduced interference of soluble
      targets: direct target capture, indirect target capture and acid dissociation.
      While indirect target capture worked well for a regular affinity antibody against
      DKK1, a high affinity antibody against PCSK9 required an additional acid
      dissociation step. The choice of a suitable format was antibody and target
      dependent. Our results offer several choices to approach immunoassay development
      for soluble targets.

PMID- 20696170
TI  - Gene therapy strategies for cardiac electrical dysfunction.
AB  - Cardiac disease is frequently associated with abnormalities in electrical
      function that can severely impair cardiac performance with potentially fatal
      consequences. The available therapeutic options have some efficacy but are far
      from perfect. The curative potential of gene therapy makes it an attractive
      approach for the treatment of cardiac arrhythmias. To date, gene therapy research
      strategies have targeted three major classes of cardiac arrhythmias: (1)
      ventricular arrhythmias, (2) atrial fibrillation, and (3) bradyarrhythmias.
      Various vehicles for gene transfer have been employed with adeno-associated viral
      gene delivery being the preferred choice for long-term gene expression and
      adenoviral gene delivery for short-term proof-of-concept work. In combination
      with the development of novel delivery methods, gene therapy may prove to be an
      effective strategy to eliminate the most debilitating of arrhythmias. This
      article is part of a Special Section entitled "Special Section: Cardiovascular
      Gene Therapy".

PMID- 20696171
TI  - Myocardial stress remodelling after regional infarction is independent of
      glycogen synthase kinase-3 inactivation.
AB  - Phosphorylation and inactivation of glycogen synthase kinase 3 (GSK-3) is
      observed in the failing heart induced by chronic pharmacological stress and
      aortic banding. Constitutive kinase activity attenuates pathological remodelling,
      suggesting an obligatory role in stress signalling. However, this has been
      challenged by recent data whereby conditional GSK-3beta deletion has been shown
      to protect against post-infarct remodelling. Here, we set out to determine the
      chronic remodelling response to infarction in hearts of GSK-3alpha/beta(Ala21/9)
      knockin (KI) mice encoding constitutively active GSK-3 isoforms. At 4 weeks after
      infarction there were significant increases in normalised heart weight and left
      ventricular (LV) muscle volume compared to sham in both KI and wild type animals.
      This was associated with an increase in LV cavity dimensions and remote LV wall
      thickness. Hypertrophy in both genotypes resulted in marked contractile
      impairment on both invasive and non-invasive interrogation. Increased
      phosphorylation of GSK-3beta, but not GSK-3alpha, was demonstrated at 1 week
      after infarction and remained elevated at 4 weeks compared to sham-treated
      hearts. In conclusion, GSK-3beta phosphorylation and inactivation occurs with,
      but is not an obligatory signalling event in, chronic post-infarct remodelling in
      the mouse heart. This highlights the heterogeneity of pathological hypertrophy
      and the divergent role of GSK-3 signalling in chronic myocardial stress.

PMID- 20696172
TI  - The effect of scale-free topology on the robustness and evolvability of genetic
      regulatory networks.
AB  - We investigate how scale-free (SF) and Erdos-Renyi (ER) topologies affect the
      interplay between evolvability and robustness of model gene regulatory networks
      with Boolean threshold dynamics. In agreement with Oikonomou and Cluzel (2006) we
      find that networks with SF(in) topologies, that is SF topology for incoming nodes
      and ER topology for outgoing nodes, are significantly more evolvable towards
      specific oscillatory targets than networks with ER topology for both incoming and
      outgoing nodes. Similar results are found for networks with SF(both) and SF(out)
      topologies. The functionality of the SF(out) topology, which most closely
      resembles the structure of biological gene networks (Babu et al., 2004), is
      compared to the ER topology in further detail through an extension to multiple
      target outputs, with either an oscillatory or a non-oscillatory nature. For
      multiple oscillatory targets of the same length, the differences between SF(out)
      and ER networks are enhanced, but for non-oscillatory targets both types of
      networks show fairly similar evolvability. We find that SF networks generate
      oscillations much more easily than ER networks do, and this may explain why SF
      networks are more evolvable than ER networks are for oscillatory phenotypes. In
      spite of their greater evolvability, we find that networks with SF(out)
      topologies are also more robust to mutations (mutational robustness) than ER
      networks. Furthermore, the SF(out) topologies are more robust to changes in
      initial conditions (environmental robustness). For both topologies, we find that
      once a population of networks has reached the target state, further neutral
      evolution can lead to an increase in both the mutational robustness and the
      environmental robustness to changes in initial conditions.

PMID- 20696173
TI  - Hydrodynamic interaction of two unsteady model microorganisms.
AB  - The study of pair-wise interactions between swimming microorganisms is
      fundamental to the understanding of the rheological and transport properties of
      semi-dilute suspensions. In this paper, the hydrodynamic interaction of two
      ciliated microorganisms is investigated numerically using a boundary-element
      method, and the microorganisms are modeled as spherical squirmers that swim by
      time-dependent surface deformations. The results show that the inclusion of the
      unsteady terms in the ciliary propulsion model has a large impact on the
      trajectories of the interacting cells, and causes a significant change in
      scattering angles with potential important consequences on the diffusion
      properties of semi-dilute suspensions. Furthermore, the analysis of the shear
      stress acting on the surface of the microorganisms revealed that the duration and
      the intensity of the near-field interaction are significantly modified by the
      presence of unsteadiness. This observation may account for the hydrodynamic
      nature of randomness in some biological reactions, and supersedes the distinction
      between intrinsic randomness and hydrodynamic interactions, adding a further
      element to the understanding and modeling of interacting microorganisms.

PMID- 20696174
TI  - Models for gibberellic acid transport and enzyme production and transport in the
      aleurone layer of barley.
AB  - Gibberellins are growth hormones produced in the embryo of grain released during
      germination. They promote growth through the production of enzymes in the
      aleurone layer surrounding the endosperm. These enzymes then diffuse into the
      endosperm and produce the sugars required by the growing acrospire. Here we model
      the transport of gibberellins into and along the aleurone layer, the consequent
      production of enzymes, and their transport into the endosperm. Simple approximate
      solutions of the governing equations are obtained which suggest that the enzymes
      are released immediately behind a gibberellin front which travels with almost
      constant speed along the aleurone layer. The model also suggests that this
      propagation speed is determined primarily by conditions near the scutellum
      aleurone junction, which may enable the embryo to actively control the
      germination process.

PMID- 20696175
TI  - 2D-MH: A web-server for generating graphic representation of protein sequences
      based on the physicochemical properties of their constituent amino acids.
AB  - Introduction of graphic representation for biological sequences can provide
      intuitive overall pictures as well as useful insights for performing large-scale
      analysis. Here, a new two-dimensional graph, called "2D-MH", is proposed to
      represent protein sequences. It is formed by incorporating the information of the
      side-chain mass of each of the constituent amino acids and its hydrophobicity.
      The graphic curve thus generated is featured by (1) an one-to-one correspondence
      relation without circuit or degeneracy, (2) better reflecting the innate
      structure of the protein sequence, (3) clear visibility in displaying the
      similarity of protein sequences, (4) more sensitive for the mutation sites
      important for drug targeting, and (5) being able to be used as a metric for the
      "evolutionary distance" of a protein from one species to the other. It is
      anticipated that the presented graphic method may become a useful vehicle for
      large-scale analysis of the avalanche of protein sequences generated in the post
      genomic age. As a web-server, 2D-MH is freely accessible at
      http://icpr.jci.jx.cn/bioinfo/pplot/2D-MH, by which one can easily generate the
      two-dimensional graphs for any number of protein sequences and compare the
      evolutionary distances between them.

PMID- 20696176
TI  - Three-dimensional cell-dense constructs containing endothelial cell-networks are
      an effective tool for in vivo and in vitro vascular biology research.
AB  - Angiogenesis is a complicated natural process, and understanding the mechanism by
      which it occurs is important for medical, pharmaceutical, and cell biological
      sciences. Many techniques for investigating angiogenesis have been reported. In
      this study, we introduced a novel application of a cell culture technique that
      can be used in in vitro and in vivo vascular biology research. Cultivated
      endothelial cells (ECs) were harvested from temperature responsive culture dishes
      by reducing the temperature, without the need for a proteinase treatment. For
      this technique, the direct contact of ECs with fibroblasts was important for the
      formation of a capillary-like network in vitro. Moreover, layered cell sheets
      containing EC-networks produced lumen and vascular structures in the three
      dimensional constructs, as well as in the construct transplanted into a living
      body. Thus, our culture technique was able to create cell sheets and three
      dimensional constructs containing EC-networks, because they preserved normal and
      intrinsic cell-cell direct contact and various cell adhesive factors. Moreover,
      the thickness of these three-dimensional (3-D) constructs could be controlled by
      the number of layered cell sheets. These observations indicated that our novel
      technology contributed to the progress of vascular biology and lead to a new tool
      that can be used in in vivo and in vitro vascular biology research.

PMID- 20696177
TI  - Could genetic analysis be useful in reducing cerebrovascular risk in hypertensive
      subjects with hyperhomocysteinemia and patent foramen ovale? A 2-year follow-up
      study.
AB  - OBJECTIVES: Potential causes of cryptogenic cerebrovascular (CV) events are
      patent foramen ovale (PFO) and hyper homocysteinemia (H-Hcys), this latter a well
      established risk factor for thrombosis particularly in the presence of mutation
      for the methylenetetrahydrofolate reductase (MTHFR) gene. This study investigated
      if in uncomplicated hypertensive subjects (HTs) with isolated PFO and H-Hcys, a
      different MTHFR polymorphism pattern for C667->T gene mutation could influence
      PFO management and to reduce the CV risk. METHODS: In thirty-two HTs aged 55.6+/
      14.4years, PFO was diagnosed by echocardiography. MTHFR genotype was evaluated by
      a multiplex polymerase chain reaction with reverse line blot hybridization assay.
      In relation to the T allele distribution, HTs were divided in normal (CC),
      heterozygote (CT) and homozygote (TT) for the MTHFR genotype. All subjects
      received a supplementation of oral folate (5mg daily) and were evaluated yearly
      for 2years. Analysis of variance for repeated measures (ANOVA) was used to
      compare changes of Hcys at baseline and at the end of follow-up and differences
      between continuous variables were evaluated in the three MTHFR groups with the
      Tukey's post hoc test after adjustment for confounders. RESULTS: At the follow
      up, Hcys levels significantly normalized from baseline both in TT (38.1+/-6.7 vs.
      15+/-3.6, p<0.01) and CT (26.6+/-2.3 vs. 9.2+/-1.6, p<0.01) but not in CC
      subjects (18.2+/-1.8 vs. 16.0+/-1.6, NS). Independently of age, BMI, vitamin
      treatment both systolic and diastolic blood pressure (BP) significantly decrease
      at the follow-up in all the MTHFR genotypes. No CV events were observed during
      the follow-up. CONCLUSIONS: In HTs with isolated PFO and H-Hcys, oral folate
      supplementation reduces Hcys levels both in TT and CT subjects with C667->T
      mutation of MTHFR. In addition the BP normalization probably contributed to
      reduce CV risk in these genotypes.

PMID- 20696178
TI  - Photosensitization induced by the antibacterial fluoroquinolone Rufloxacin leads
      to mutagenesis in yeast.
AB  - Rufloxacin (RFX) is an antibacterial fluoroquinolone that exhibits UVA
      photosensitization properties. Photosensitization reactions lead to the formation
      of oxidative damage, mainly via singlet oxygen. Here we explore the phototoxic
      and photomutagenic potency of RFX using a panel of yeast (Saccharomyces
      cerevisiae) mutants affected in different DNA repair pathways. Yeast mutants
      provide a sensitive tool to identify the photodamage and the DNA repair pathways
      that cope with it. Cell viability test at increasing dose of UVA shows that both
      the DNA repair deficient and wild type cells are equally sensitive to RFX-induced
      photosensitization, demonstrating that phototoxic effect is not due to DNA
      injury. Photomutagenicity of RFX is evaluated by measuring the frequency of
      forward Can(R) mutations. The mutation induction is low in wild type cells. A
      high increase in mutation frequency is observed in strains affected in Ogg1 gene,
      compared to wild type and other base excision repair deficient strains. The
      mutation spectrum photomediated by RFX in wild type cells reveals a bias in
      favour of GC>TA transversions, whereas transition and frameshift mutations are
      less represented. Altogether data demonstrates that 8-oxo-7,8-dihydroguanine (8
      oxoGua) is by far the major DNA damage produced by RFX photosensitization,
      leading to mutagenesis. We also explore the role played by DNA mismatch repair,
      translesion synthesis and post-replication repair in the prevention of mutagenic
      effects due to RFX exposure. In addition, we show that most of RFX
      photodegradation products are not mutagenic. This study defines the phototoxic
      and photomutagenic properties of antibacterial RFX and point out possible
      unwanted side effects in skin under sunlight.

PMID- 20696179
TI  - Occupancy of human brain GABA(A) receptors by the novel alpha5 subtype-selective
      benzodiazepine site inverse agonist alpha5IA as measured using [11C]flumazenil
      PET imaging.
AB  - GABA(A) receptor alpha5-selective inverse agonists enhance cognitive performance
      in pre-clinical species. However, a key aspect of the clinical development of
      such compounds is the demonstration that in man such compounds are devoid of the
      anxiogenic-like activity associated with non-selective inverse agonists such as
      FG 7142. The triazolophthalazine alpha5IA (3-(5-methylisoxazol-3-yl)-6-[(1-methyl
      1,2,3-triazol-4-yl)methyloxy]-1,2,4-triazolo[3,4-a]phthalazine) is an alpha5
      selective inverse agonist which enhances cognitive performance in rodents and
      encouragingly in human Phase I Safety and Tolerability studies it was devoid of
      the anxiogenic-like activity associated with FG 7142. However, in order to
      appropriately interpret this latter observation, it was considered important to
      demonstrate that the absence of anxiogenic-like activity occurs at significant
      levels of receptor occupancy. Consequently, the occupancy of human brain GABA(A)
      receptors was measured using [11C]flumazenil positron emission tomography in
      three healthy normal young male volunteers following a single oral dose of 2 mg
      alpha5IA. One hour after dosing, mean occupancy levels were 53% and this fell to
      16% by 8 h post-dose, with the plasma alpha5IA concentration corresponding to 50%
      occupancy being 10 ng/mL. These data clearly show that an alpha5-selective
      inverse agonist is not associated with anxiogenic-like side effects at doses that
      give ~50% occupancy.

PMID- 20696180
TI  - The influence of mood on the processing of syntactic anomalies: evidence from
      P600.
AB  - In several domains of psychology it has been shown that mood influences the way
      in which we process information. So far, little is known about the relation
      between mood and processes of language comprehension. In the present study we
      explore, whether, and if so how, mood affects the processing of syntactic
      anomalies in real time by recording event-related potentials (ERPs). To this aim
      we compared the P600 effect to subject-verb agreement errors relative to correct
      sentences while ERPs were recorded and mood was manipulated by presenting happy
      or sad film clips. The prediction was that if emotional state affects processes
      of language comprehension this should be reflected by an interaction between mood
      and P600. The results were as follows: first, the mood induction procedure was
      effective: participants were happier after watching happy film clips and sadder
      after watching sad film clips compared to baseline. Second, for P600 a mood by
      syntactic correctness interaction was obtained for the midline and lateral
      electrodes. The interaction reflected a broadly distributed P600 effect for the
      happy mood condition and a strong reduction in P600 effect for the sad mood
      condition. Correlation analyses confirmed that the observed changes in P600
      effect were accompanied by reliable changes in emotional state. The present ERP
      findings demonstrate that mood interacts with processes of language
      comprehension. Three possible explanations for the mood by syntactic correctness
      interaction are discussed; one in terms of syntactic processing, one in terms of
      heuristic processing, and one in terms of more general factors like attention
      and/or motivation.

PMID- 20696181
TI  - Gender markedly modulates behavioral thermoregulation in a non-human primate
      species, the mouse lemur (Microcebus murinus).
AB  - Age and gender are known to significantly modulate thermoregulatory capacities in
      mammals, suggesting strong impacts on behavioral adjustments, which are used to
      minimize the energy costs of thermoregulation. We tested the effects of sex and
      age on spontaneous choice of ambient temperature (Ta) in a non-human primate
      species, the mouse lemur (Microcebus murinus). The animals acclimated to both
      winter and summer photoperiods, two seasons significantly modifying
      thermoregulation function, were experimented in a thermal gradient device. During
      winter, adult males did not show preference for warm Tas whereas old males did.
      In contrast, female mouse lemurs of both age categories exhibited great
      preferences for warm Tas. Acclimation to summer revealed that males selected
      colder Ta for the day than during the night. Such behavior did not exist in
      females. Old females explored and selected warmer nests than adult ones. This
      study raised novel issues on the effect of gender on thermoregulatory capacities
      in the mouse lemur. Females probably use behavioral adjustments to limit energy
      expenditure and might prefer to preserve energy for maternal investment by
      anticipation of and during the breeding season. Further experiments focusing on
      female thermoregulatory capacities are needed to better understand the energy
      challenge that may occur during winter and summer in female mouse lemurs, and
      whether this trade-off changes during aging.

PMID- 20696182
TI  - Features and the 'primal sketch'.
AB  - This review is concerned primarily with psychophysical and physiological evidence
      relevant to the question of the existence of spatial features or spatial
      primitives in human vision. The review will be almost exclusively confined to
      features defined in the luminance domain. The emphasis will be on the
      experimental and computational methods that have been used for revealing
      features, rather than on a detailed comparison between different models of
      feature extraction. Color and texture fall largely outside the scope of the
      review, though the principles may be similar. Stereo matching and motion matching
      are also largely excluded because they are covered in other contributions to this
      volume, although both have addressed the question of the spatial primitives
      involved in matching. Similarities between different psychophysically-based model
      will be emphasized rather than minor differences. All the models considered in
      the review are based on the extraction of directional spatial derivatives of the
      luminance profile, typically the first and second, but in one case the third
      order, and all have some form of non-linearity, be it rectification or
      thresholding.

PMID- 20696183
TI  - Neurotransmitters excreted in the urine as biomarkers of nervous system activity:
      validity and clinical applicability.
AB  - Strategies for managing the nervous system are numerous while methods of
      evaluating the nervous system are limited. Given the physiological importance of
      neurotransmitters as signaling molecules in the nervous system, the measurement
      of neurotransmitters has significant potential as a clinical tool. Of all the
      biological fluids that can be utilized, urinary neurotransmitter testing, due to
      its stability, sensitivity, and non-invasiveness, is the desired method to
      analyze nervous system function. Increasing use of this technology in a clinical
      setting demands a review of its feasibility, utility, and clinical value. We
      review the current body of literature pertaining to the mechanism of
      neurotransmitter transport across the blood-brain barrier as well as
      neurotransmitter filtration and excretion by the kidneys. In addition, this
      review summarizes the historical use of urinary neurotransmitter assessment to
      diagnose pheochromocytoma. Early research also correlated urinary assessment of
      neurotransmitters to various clinical symptoms and treatments of which we present
      research only for depression, ADHD, and inflammation because of the abundant
      amount of research in these areas. Finally, we review the limitations and
      challenges of urinary neurotransmitter testing. Taken together, evidence suggests
      that neurotransmitters excreted in the urine may have a place in clinical
      practice as a biomarker of nervous system function to effectively assess
      disturbances and monitor treatment efficacy.

PMID- 20696184
TI  - The impact of neonatal bisphenol-A exposure on sexually dimorphic hypothalamic
      nuclei in the female rat.
AB  - Now under intense scrutiny, due to its endocrine disrupting properties, the
      potential threat the plastics component bisphenol-A (BPA) poses to human health
      remains unclear. Found in a multitude of polycarbonate plastics, food and
      beverage containers, and medical equipment, BPA is thought to bind to estrogen
      receptors (ERs), thereby interfering with estrogen-dependent processes. Our lab
      has previously shown that exposure to BPA (50mg/kg bw or 50MUg/kg bw) during the
      neonatal critical period is associated with advancement of puberty, early
      reproductive senescence and ovarian malformations in female Long Evans rats.
      Here, using neural tissue obtained from the same animals, we explored the impact
      of neonatal BPA exposure on the development of sexually dimorphic hypothalamic
      regions critical for female reproductive physiology and behavior. Endpoints
      included quantification of oxytocin-immunoreactive neurons (OT-ir) in the
      paraventricular nucleus (PVN), serotonin (5-HT-ir) fiber density in the
      ventrolateral subdivision of the ventromedial nucleus (VMNvl) as well as ERalpha
      ir neuron number in the medial preoptic area (MPOA), the VMNvl, and the arcuate
      nucleus (ARC). Both doses of BPA increased the number of OT-ir neurons within the
      PVN, but no significant effects were seen on 5-HT-ir fiber density or ERalpha-ir
      neuron number in any of the areas analyzed. In addition to hypothalamic
      development, we also assessed female sex behavior and body weight. No effect of
      BPA on sexual receptivity or proceptive behavior in females was observed. Females
      treated with BPA, however, weighed significantly more than control females by
      postnatal day 99. This effect of BPA on weight is critical because alterations in
      metabolism, are frequently associated with reproductive dysfunction.
      Collectively, the results of this and our prior study indicate that the impact of
      neonatal BPA exposure within the female rat hypothalamus is region specific and
      support the hypothesis that developmental BPA exposure may adversely affect
      reproductive development in females.

PMID- 20696185
TI  - Differential regulation of AKT, MAPK and GSK3beta during C2-ceramide-induced
      neuronal death.
AB  - Evidence has implicated apoptosis as a mechanism underlying cell demise in
      diverse neurodegenerative diseases including Parkinson's disease (PD). Endogenous
      toxins and other stress signals activate the sphingomyelin pathway increasing the
      levels of ceramide, an important regulator of cell death. In the present paper we
      have analysed the contribution of PI3K/AKT-GSK3beta and MAPK (ERK and JNK)
      pathways to cell death in a catecholaminergic cell line following exposure to
      C(2)-ceramide. We also explored the potential neuroprotective action of insulin
      like growth factor-1 (IGF-1) and neurotrophin-3 (NT3). We demonstrated that C(2)
      ceramide-induced cell death is associated to an early decrease in phosphorylation
      (inhibition) of PI3K/AKT and ERK, followed by phosphorylation (activation) of JNK
      and de-phosphorylation (activation) of glycogen synthase kinase-3 beta
      (GSK3beta). NT3 and IGF-1 increased survival at early time points, but only IGF-1
      is capable to attenuate C(2)-ceramide-mediated neuronal death, and this
      neuroprotection is associated to strong and permanent activation of AKT and
      inhibition of GSK3beta. In conclusion, C(2)-ceramide initiates a series of events
      including an early inactivation of PI3K/AKT and ERK pathways followed by
      activation of JNK and activation of GSK3beta and neuronal death, changes that are
      counteracted by IGF-1.

PMID- 20696186
TI  - Branched thalamic afferents: what are the messages that they relay to the cortex?
AB  - Many of the axons that carry messages to the thalamus for relay to the cerebral
      cortex are branched in a pattern long known from Golgi preparations. They send
      one branch to the thalamus and the other to motor centers of the brainstem or
      spinal cord. Because the thalamic branches necessarily carry copies of the motor
      instructions their messages have the properties of efference copies. That is,
      they can be regarded as providing reliable information about impending
      instructions contributing to movements that will produce changes in inputs to
      receptors, thus allowing neural centers to compensate for these changes of input.
      We consider how a sensory pathway like the medial lemniscus, the spinothalamic
      tract or the optic tract can also be seen to act as a pathway for an efference
      copy. The direct connections that ascending and cortical inputs to the thalamus
      also establish to motor outputs create sensorimotor relationships that provide
      cortex with a model of activity in lower circuits and link the sensory and the
      motor sides of behavior more tightly than can be expected from motor outputs with
      a single, central origin. These transthalamic connectional patterns differ from
      classical models of separate neural pathways for carrying efference copies of
      actions generated at higher levels, and introduce some different functional
      possibilities.

PMID- 20696187
TI  - Seasonal regulation of social communication by photoperiod and testosterone:
      effects of arginine-vasopressin, serotonin and galanin in the medial preoptic
      area-anterior hypothalamus.
AB  - Arginine-vasopressin (AVP) activation of V1a AVP receptors in the medial preoptic
      area-anterior hypothalamus (MPOA-AH) plays a critical role in the control of a
      form of social communication called flank marking. The ability of AVP and V1a
      receptors in the MPOA-AH to regulate flank marking is modulated by a number of
      factors including galanin (GAL), serotonin (5-HT) and gonadal hormones. More
      recent studies suggest that there may be seasonal differences in the number or
      type of AVP receptors in the MPOA-AH controlling flank marking or in the
      modulation of these mechanisms by GAL or 5-HT. The purpose of the present study
      was to examine how exposure to "summer-like" and "winter-like" photoperiods
      alters the neural mechanisms regulating flank marking. These studies confirmed
      that V1a AVP receptors, but not V1b AVP receptors play a significant role in
      controlling flank marking in the MPOA-AH in both LP and SP-housed hamsters. These
      studies also found that there were no significant differences between hamsters
      housed in LP and SP in the ability of serotonin 5-HT1a/7 and 5-HT1b receptor
      agonists injected into the MPOA-AH to inhibit odor-induced flank marking.
      Finally, these studies found that GAL could significantly inhibit the ability of
      AVP to stimulate flank marking in SP-housed hamsters and that there were no
      differences between hamsters housed in LP and SP in the ability of a GAL
      antagonist to inhibit AVP-induced flank marking. The present study confirms that
      V1a receptors are critical for AVP regulation of flank marking and that
      photoperiodic mechanisms do not alter the modulation of flank marking by GAL or 5
      HT in the MPOA-AH.

PMID- 20696188
TI  - Rat psychomotor vigilance task with fast response times using a conditioned lick
      behavior.
AB  - Investigations into the physiological mechanisms of sleep control require an
      animal psychomotor vigilance task (PVT) with fast response times (<300 ms). Rats
      provide a good PVT model since whisker stimulation produces a rapid and robust
      cortical evoked response, and animals can be trained to lick following
      stimulation. Our prior experiments used deprivation-based approaches to maximize
      motivation for operant conditioned responses. However, deprivation can influence
      physiological and neurobehavioral effects. In order to maintain motivation
      without water deprivation, we conditioned rats for immobilization and head
      restraint, then trained them to lick for a 10% sucrose solution in response to
      whisker stimulation. After approximately 8 training sessions, animals produced
      greater than 80% correct hits to the stimulus. Over the course of training,
      reaction times became faster and correct hits increased. Performance in the PVT
      was examined after 3, 6 and 12 h of sleep deprivation achieved by gentle
      handling. A significant decrease in percent correct hits occurred following 6 and
      12 h of sleep deprivation and reaction times increased significantly following 12
      h of sleep deprivation. While behaviorally the animals appeared to be awake, we
      observed significant increases in EEG delta power prior to misses. The rat PVT
      with fast response times allows investigation of sleep deprivation effects, time
      on-task and pharmacological agents. Fast response times also allow closer
      parallel studies to ongoing human protocols.

PMID- 20696189
TI  - Comparative neuroprotective profile of statins in quinolinic acid induced
      neurotoxicity in rats.
AB  - A possible neuroprotective role has been recently suggested for 3H3MGCoA
      reductase inhibitors (statins). Here, we sought to determine neuroprotective
      effect of statins in quinolinic acid induced neurotoxicity in rats. Rats were
      surgically administered quinolinic acid and treated with Atorvastatin (10, 20
      mg/kg), simvastatin (15, 30 mg/kg) and fluvastatin (5, 10 mg/kg) once daily up to
      3 weeks. Atorvastatin (10, 20 mg/kg), simvastatin (30 mg/kg) and fluvastatin (10
      mg/kg) treatment significantly attenuated the quinolinic acid induced behavioral
      (locomotor activity, rotarod performance and beam walk test), biochemical (lipid
      peroxidation, nitrite concentration, SOD and catalase), mitochondrial enzyme
      complex alterations in rats suggesting their free radical scavenging potential.
      Additionally, atorvastatin (10, 20 mg/kg), simvastatin (30 mg/kg) and fluvastatin
      (10 mg/kg) significantly decrease the TNF-alpha level and striatal lesion volume
      in quinolinic acid treated animals indicating their anti-inflammatory effects. In
      comparing the protective effect of different statins, atorvastatin is effective
      at both the doses while simvastatin and fluvastatins at respective lower doses
      were not able to produce the protective effect in quinolinic acid treated
      animals. These modulations can account, at least partly, for the beneficial
      effect of statins in our rodent model of striatal degeneration. Our findings show
      that statins could be explored as possible neuroprotective agents for
      neurodegenerative disorders such as HD.

PMID- 20696190
TI  - Frontal theta and alpha power and coherence changes are modulated by semantic
      complexity in Go/NoGo tasks.
AB  - To study the interactions between semantic processing and motor response
      inhibition, we recorded scalp EEG as subjects performed a series of Go/NoGo
      response inhibition tasks whose response criteria depended on different levels of
      semantic processing. Three different tasks were used. The first required the
      subject to make a Go/NoGo decision based on pictures of one particular car or one
      particular dog. The second used pictures of different types of cars and of dogs,
      and the final task used stimuli that ranged across multiple types of objects and
      animals. We found that the theta-band EEG power recorded during the NoGo response
      was attenuated as a function of semantic complexity while the peak latency was
      delayed in only the most complex category task. Further, frontal alpha-band
      desynchronization was strongest for the simplest task and remained close to
      baseline for the other tasks. Finally, there was significant theta-band coherence
      between the frontal pole and pre-SMA for the NoGo conditions across tasks, which
      was not found in the Go trials. These findings provide information about how more
      rostral frontal regions interact with the pre-SMA during response inhibition
      across different stimuli and task demands: specifically, level of processing
      affects latency, difficulty affects amplitude, and coherence is affected by
      whether the decision is Go or NoGo.

PMID- 20696191
TI  - Expansion and hepatic differentiation of rat multipotent adult progenitor cells
      in microcarrier suspension culture.
AB  - Many potential applications of stem cells require large quantities of cells,
      especially those involving large organs such as the liver. For such applications,
      a scalable reactor system is desirable to ensure a reliable supply of sufficient
      quantities of differentiation competent or differentiated cells. We employed a
      microcarrier culture system for the expansion of undifferentiated rat multipotent
      adult progenitor cells (rMAPC) as well as for directed differentiation of these
      cells to hepatocyte-like cells. During the 4-day expansion culture, cell
      concentration increased by 85-fold while expression level of pluripotency markers
      were maintained, as well as the MAPC differentiation potential. Directed
      differentiation into hepatocyte-like cells on the microcarriers themselves gave
      comparable results as observed with cells cultured in static cultures. The cells
      expressed several mature hepatocyte-lineage genes and asialoglycoprotein receptor
      1 (ASGPR-1) surface protein, and secreted albumin and urea. Microcarrier culture
      thus offers the potential of large-scale expansion and differentiation of stem
      cells in a more controlled bioreactor environment.

PMID- 20696192
TI  - Optimizing the secondary structure of human papillomavirus type 16 L1 mRNA
      enhances L1 protein expression in Saccharomyces cerevisiae.
AB  - Human papillomavirus (HPV) type 16 is the most significant type in the
      prophylactic vaccine field because 50-60% of cervical cancer cases are caused by
      infection with HPV type 16. The L1 protein, which is the highly immunogenic major
      capsid protein of HPV, is the major component of the prophylactic vaccine. To
      enhance L1 protein expression in Saccharomyces cerevisiae we used a strategy
      involving the modification of the HPV16 L1 gene (MO) to reduce the amount of
      predicted mRNA secondary structure, rather than a strategy aiming at optimizing
      codon bias as has often been used to enhance the expression of foreign genes. The
      mean expression level of L1 protein in MO-transformed candidates was four-fold
      higher than in cells transformed with the wild type HPV16 L1 gene (WT), while the
      fraction of L1 mRNA transcribed from MO in total RNA was four-fold lower than
      with L1 mRNA transcribed from WT. This demonstrates that L1 protein expression in
      MO-transformed cells was increased by a post-transcriptional mechanism. The L1
      protein produced in MO-transformed cells self-assembled into virus-like particles
      (VLP) with features similar to those of the native virion. These results indicate
      that the strategy of optimizing the secondary structure of HPV16 L1 mRNA was
      successful in increasing L1 protein expression in Saccharomyces cerevisiae.

PMID- 20696193
TI  - The PRRSV replicase: exploring the multifunctionality of an intriguing set of
      nonstructural proteins.
AB  - Our knowledge about the structure and function of the nonstructural proteins
      (nsps) encoded by the arterivirus replicase gene has advanced in recent years.
      The continued characterization of the nsps of the arterivirus prototype equine
      arteritis virus has not only corroborated several important functional
      predictions, but also revealed various novel features of arteriviral replication.
      For porcine reproductive and respiratory syndrome virus (PRRSV), based on
      bioinformatics predictions and experimental studies, a processing map for the
      pp1a and pp1ab replicase polyproteins has been developed. Crystal structures have
      been resolved for two of the PRRSV nonstructural proteins that possess proteinase
      activity (nsp1alpha and nsp4). The functional characterization of the key enzymes
      for arterivirus RNA synthesis, the nsp9 RNA polymerase and nsp10 helicase, has
      been initiated. In addition, progress has been made on nsp functions relating to
      the regulation of subgenomic mRNAs synthesis (nsp1), the induction of replication
      associated membrane rearrangements (nsp2 and nsp3), and an intriguing replicative
      endoribonuclease (nsp11) for which the natural substrate remains to be
      identified. The role of nsps in viral pathogenesis and host immunity is also
      being explored, and specific nsps (including nsp1alpha/beta, nsp2, nsp4, nsp7,
      and nsp11) have been implicated in the modulation of host immune responses to
      PRRSV infection. The nsp3-8 region was identified as containing major virulence
      factors, although mechanistic information is scarce. The biological significance
      of PRRSV nsps in virus-host interactions and the technical advancements in
      engineering the PRRSV genome by reverse genetics are also reflected in recent
      developments in the area of vaccines and diagnostic assays.

PMID- 20696194
TI  - An ultrasound-responsive nano delivery system of tissue-type plasminogen
      activator for thrombolytic therapy.
AB  - This study is undertaken to design a novel nano-sized delivery system of tissue
      type plasminogen activator (t-PA) which has a suppressed thrombolytic activity of
      t-PA, but recovered the activity only when exposed to ultrasound. Various amounts
      of ethylenediamine were chemically introduced into gelatin (cationized gelatins)
      to complex with t-PA. To modify the surface of complexes with polyethylene glycol
      (PEG), PEG was chemically grafted to the anionic gelatin (PEG-gelatin). The
      simple mixing with the PEG-gelatin enabled the t-PA-cationized gelatin complex to
      form a nano-sized delivery complex with PEG chains on the surface. The t-PA
      activity of PEG-modified complexes was significantly suppressed to be 45% of
      original t-PA. However, when exposed to ultrasound in vitro, the t-PA activity
      was fully recovered. A cell culture experiment demonstrated no cytotoxicity of
      PEG-modified complexes. The body distribution study indicated that the half-life
      of t-PA in the blood circulation was prolonged about 3 times. In a rabbit
      thrombosis model, the intravenous administration of PEG-modified complexes
      followed by ultrasound irradiation resulted in complete recanalization, in
      remarked contrast to the complex administration alone. It is concluded that the
      PEG-modified complex is a promising t-PA delivery system to enhance the
      biological activity at the site necessary only by a local ultrasound irradiation.

PMID- 20696195
TI  - Amyloid precursor protein gene mutated at Swedish 670/671 sites in vitro induces
      changed expression of nicotinic acetylcholine receptors and neurotoxicity.
AB  - In order to investigate the influence of amyloid precursor protein (APP) over
      expression on the levels of nicotinic acetylcholine receptors (nAChRs), the pCDNA
      3.0 carrying the Swedish 670/671 APP double mutation (APP(SWE)) gene was
      transfected into human neuroblastoma (SH-SY5Y) cells and primary culture of rat
      hippocampal neurons. The mRNA level of APP, and nAChR alpha3, alpha4 and alpha7
      subunits were detected by real-time PCR, and their corresponding proteins as well
      as alpha-secreted APP (alphaAPPs) by Western blotting. [3H]Epibatidine binding
      sites were measured by the receptor binding assay. The results showed that
      significantly concomitant increases in mRNA and protein levels of SH-SY5Y cells
      and primary cultured neurons transfected with APP(SWE) were observed.
      Interestingly, a decreased alphaAPPs level was detected in both cells treated
      with APP(SWE) transfection. In addition, decreases in mRNA and protein levels of
      alpha3 nAChR subunit in SH-SY5Y cells or alpha4 subunit in primary cultured
      neurons with APP(SWE) transfection were observed. For alpha7 nAChR, the increased
      protein and mRNA levels were found in SH-SY5Y cells and primary cultured neurons
      with APP(SWE) transfection. The number of cholinergic receptor binding site of
      [3H]epibatidine was decreased in the SH-SY5Y cells transfected with APP(SWE).
      Elevations in the activities of AChE and BuChE and in the level of lipid
      peroxidation were detected in both types of cultured cells transfected with
      APP(SWE). These results indicated that the over-expression of APP(SWE) gene can
      influence the expression of nAChRs and resulted in neurotoxicity, in which this
      process might play an important role in the pathogenesis of Alzheimer's disease.

PMID- 20696196
TI  - Dietary acrylamide exposure and hemoglobin adducts--National Health and Nutrition
      Examination Survey (2003-04).
AB  - The objective of this study is to evaluate the relationship between dietary AA
      and hemoglobin adducts using the National Health and Nutrition Examination Survey
      (NHANES, 2003-04). Measured acrylamide (AA-Hb) and glycidamide (Gly-Hb)
      hemoglobin adducts for over 7000 participants >3 years, 24-h dietary recall, food
      frequency questionnaire (FFQ), lifestyle and demographic data, and anthropometric
      measurements are available from NHANES (2003-04). The 24-h dietary recall and FFQ
      data were combined with AA concentration data in food from the US FDA to estimate
      "usual" AA dietary exposure. The associations between dietary AA and AA-Hb and
      Gly-Hb were evaluated using linear regression models with smoking, age, gender,
      energy and macronutrient intake, body surface area, and activity level as
      covariates. Dietary AA positively correlates with AA-Hb and Gly-Hb (p<0.05) but
      the correlation is small (R-Squared<3.5%). Relative to the background adduct
      levels, the incremental increase in AA-Hb and Gly-Hb from average dietary AA is
      small (7% and 9% for AA-Hb and Gly-Hb, respectively). Non-dietary sources of
      exposure, measurement errors associated with the use of the FFQ, and uncertainty
      in the data on AA levels in foods are possible explanations for the observed lack
      of association between dietary AA and AA-Hb and Gly-Hb.

PMID- 20696197
TI  - Towards the re-introduction of grass pea (Lathyrus sativus) in the West Balkan
      Countries: the case of Serbia and Srpska (Bosnia and Herzegovina).
AB  - Vetchlings (Lathyrus spp.) are widely distributed in both Serbia and Srpska, and
      represent a valuable component of local floras all over the Balkan Peninsula.
      Despite this and the existence of a traditional Serbian name for grass pea
      (Lathyrus sativus L.), sastrica, and a pan-Slavic name for all vetchlings,
      grahor, today they are almost forgotten crops. The joint action of the Institute
      of Field and Vegetable Crops and the Faculty of Agriculture is aimed at re
      introducing grass pea and other vetchlings as multifunctional crops. Within the
      legume collection in the Institute of Field and Vegetable Crops, a small Lathyrus
      spp. collection, including about 100 accessions of 16 species, most of them being
      grass pea, was established in 2002. The landraces of grass pea were collected in
      several regions of Serbia and Srpska, where they are used for human consumption.
      Grass pea is commonly used boiled and along with other pulses, with no reports on
      lathyrism among the local people. The first Serbian breeding programme in Novi
      Sad produced already two grass pea lines that were registered in November 2009
      under the names of Studenica and Sitnica, developed from the crosses of Polish
      cultivars and local Serbian landraces.

PMID- 20696198
TI  - Usage pattern of personal care products in California households.
AB  - Given the concern over the potential for health risks associated with certain
      ingredients (e.g., phthalates) in personal care products, usage patterns of ~30
      types of personal care products (e.g., shampoo, sunscreen, fragrance, etc.) were
      collected in 604 California households through a telephone interview. Preferences
      in selecting products, e.g., scented or unscented, aerosol, and brand loyalty,
      were also investigated. Participants were recruited in three age groups, children
      (mostly preschoolers), their parents, and adults age 55 or older. Use frequencies
      of various product types varied by sex, age group, race, education, and climatic
      region. Product use by parent and child from the same household were correlated.
      Use frequencies of products in the same class (e.g., skincare) were moderately
      correlated, which may impact aggregate exposures. Use frequencies observed in
      this study were generally in the same range as those reported in the EPA Exposure
      Factor Handbook, but we found differences for some individual products. Our study
      provides additional data on population-based usage patterns of a large collection
      of commonly used personal care products pertaining to several age groups and
      socio-demographic strata. This information will be valuable for exposure and risk
      assessments.

PMID- 20696199
TI  - Biological response and morphological assessment of individually dispersed multi
      wall carbon nanotubes in the lung after intratracheal instillation in rats.
AB  - Biological responses of multi-wall carbon nanotubes (MWCNTs) were assessed after
      a single intratracheal instillation in rats. The diameter and median length of
      the MWCNTs used in this study were approximately 60 nm and 1.5 MUm, respectively.
      Groups of male Sprague-Dawley rats were intratracheally instilled with 0.04, 0.2,
      or 1 mg/kg of the individually dispersed MWCNT suspension. After instillation,
      the bronchoalveolar lavage fluid was assessed for inflammatory cells and markers,
      and the lung, liver, kidney, spleen, and cerebrum were histopathologically
      evaluated at 3-day, 1-week, 1-month, 3-month, and 6-month post-exposure.
      Transient pulmonary inflammatory responses were observed only in the lungs of the
      group of rats exposed to 1 mg/kg of MWCNTs. Morphology of the instilled MWCNTs in
      the lungs of rats was assessed using light microscopy and transmission electron
      microscopy (TEM). Light microscopy examination revealed that MWCNTs deposited in
      the lungs of the rats were typically phagocytosed by the alveolar macrophages and
      these macrophages were consequently accumulated in the alveoli until 6-month post
      exposure. The 400 TEM images obtained showed that all MWCNTs were located in the
      alveolar macrophages or macrophages in the interstitial tissues, and MWCNTs were
      not located in the cells of the interstitial tissues. There was no evidence of
      chronic inflammation, such as angiogenesis or fibrosis, induced by MWCNT
      instillation. These results suggest that MWCNTs were being processed and cleared
      by alveolar macrophages.

PMID- 20696200
TI  - Low molecular weight thiols reduce thimerosal neurotoxicity in vitro: modulation
      by proteins.
AB  - Thimerosal (TH), an ethylmercury complex of thiosalicylic acid has been used as
      preservative in vaccines. In vitro neurotoxicity of TH at high nM concentrations
      has been reported. Although a number of toxicological experiments demonstrated
      high affinity of mercury to thiol groups of the extracellular amino acids and
      proteins that may decrease concentration of free TH in the organism, less is
      known about the role of interactions between proteins and amino acids in
      protection against TH neurotoxicity. In the present study we examined whether the
      presence of serum proteins and of l-cysteine (Cys), d,l-homocysteine (Hcy), N
      acetyl cysteine (NAC), l-methionine (Met) and glutathione (GSH) in the incubation
      medium affects the TH-induced changes in the viability, the intracellular levels
      of calcium and zinc and mitochondrial membrane potential in primary cultures of
      rat cerebellar granule cells. The cells were exposed to 500 nM TH for 48 h or to
      15-25 MUM TH for 10 min. Our results demonstrated a decrease in the cells
      viability evoked by TH, which could be prevented partially by serum proteins,
      albumin or in a dose-dependent manner by 60, 120 or 600 MUM Cys, Hcy, NAC and
      GSH, but not by Met. This neuroprotection was less pronounced in the presence of
      proteins. Incubation of neurons with TH also induced the rise in the
      intracellular calcium and zinc concentration and decrease in mitochondrial
      membrane potential, and these effects were abolished by all the sulfur containing
      compounds studied and administered at 600 MUM concentration, except Met. The loss
      of the ethylmercury moiety from TH as a result of interaction with thiols studied
      was monitored by (1)H NMR spectroscopy. This extracellular process may be
      responsible for the neuroprotection seen in the cerebellar cell cultures, but
      also provides a molecular pathway for redistribution of TH-derived toxic
      ethylmercury in the organism. In conclusion, these results confirmed that
      proteins and sulfur-containing amino acids applied separately reduce TH
      neurotoxicity, while their combination modulates in more complex way neuronal
      survival in the presence of TH.

PMID- 20696201
TI  - Relationship between dental erosion and respiratory symptoms in patients with
      gastro-oesophageal reflux disease.
AB  - OBJECTIVES: Both dental erosion and respiratory symptoms are extra-oesophageal
      manifestations of gastro-oesophageal reflux disease (GERD). The aim of this study
      was to determine whether dental erosion was correlated with respiratory symptoms
      in GERD patients. METHODS: 88 GERD patients were recruited and assigned to three
      groups mainly according to the frequency of respiratory symptoms: Group I: never;
      Group II: occasional (1-2 days a week or less); Group III: frequent (3-5 days a
      week or more). All patients underwent medical evaluations, including medical
      history, questionnaire answering and alimentary tract examinations. Dental
      examinations were carried out on these patients and 36 healthy controls. Dental
      erosions were measured by modified method of Smith and Knight Tooth Wear Index
      (TWI). Location and severity of dental erosion were recorded. RESULTS: The
      prevalence of dental erosion in Group III (64.52%) was higher (p<0.05) than that
      in Groups I (36.67%) and II (44.44%). GERD patients were presented with dental
      erosion with TWI scores ranging from 1 to 4. Though proportion of dental erosion
      with Score 2 (7/20) in Group III was higher than that in Group I (2/11) and Group
      II (3/12), there was no statistical significance in the proportions of erosion
      scores among three patient groups. Correlation coefficient between airway
      symptoms and scores of dental erosion was 0.231 (p<0.05). Palatal erosion of
      upper incisor was seen in 8 persons (72.7%) in Group I, 9 persons (75%) in Group
      II and 16 persons (80%) in Group III (p>0.05). Labial erosion of upper incisors
      was found in 1 person in Groups I and II respectively and 4 persons in Group III.
      All patients with labial erosion on upper incisors had palatal erosion, except 1
      patient in Group III. CONCLUSIONS: In GERD patients, dental erosions are more
      prevalent in patients with frequent respiratory symptoms than those in patients
      with occasional and without respiratory symptoms. Palatal erosion of upper
      incisor is the main manifestation in patients. Acid reflux is the main causative
      factor of dental erosion in GERD patients with airway symptoms.

PMID- 20696202
TI  - Effects of cementum-dentine junction and cementum on the mechanical response of
      tooth supporting structure.
AB  - OBJECTIVES: The aim of the present work is to investigate the effects of cementum
      dentine junction (CDJ) and cementum on the stress distribution in the periodontal
      ligament (PDL) and alveolar bone. METHODS: Based on the anatomical profiles and
      the recently reported theories about the tooth attachment mechanism, the finite
      element (FE) model of a mandibular second premolar along with its detailed
      supporting structures was developed. The effect of CDJ and cementum was evaluated
      by comparing the resulting stresses of FE models of the second mandibular
      premolar with and without CDJ and cementum in tooth supporting structure.
      RESULTS: The stress levels are higher in the structure without CDJ and cementum
      than that with CDJ and cementum. The function of CDJ and cementum is as a cushion
      pad decreasing the stress in the PDL and alveolar bone under loading.
      CONCLUSIONS: As a major result of this study, it can be concluded that the CDJ
      and cementum significantly influence the stress distribution within the tooth
      supporting structure. However, most of the reported FE analysis did not take CDJ
      and cementum into account, which possibly resulted in overestimated stress values
      in the PDL and alveolar bone. From a bio-engineering perspective, the results of
      this study provide guidance for the design of dental implants and the application
      of orthodontic force system as well.

PMID- 20696203
TI  - Third generation of matrix metalloprotease inhibitors: Gain in selectivity by
      targeting the depth of the S1' cavity.
AB  - Following the disappointment of clinical trials with early broad-spectrum
      synthetic inhibitors of matrix metalloproteases (MMPs), the field is now
      resurging with a new focus on the development of more selective inhibitors.
      Compounds able to fully discriminate between different members of the MMP family
      are sorely needed for therapeutic applications. Chemical efforts over the past
      years have led to very few selective inhibitors of MMPs. The over-exploitation of
      the hydroxamate function, or other strong zinc-binding groups, might be
      responsible for this failure. By resorting to weaker zinc-chelating groups, like
      phosphoryl or carboxylic groups, inhibitors with improved selectivity profiles
      have been developed. However, the most encouraging results have been obtained
      with compounds that avoid targeting the zinc but gain their affinity from
      plunging deeper into the MMP S(1)' cavity. Analyses of the crystal structures of
      MMP-13 and MMP-8 complexes with such compounds provide novel insights for the
      design of more selective inhibitors for other members of the MMP family.

PMID- 20696204
TI  - The molecular characterization of a novel GH38 alpha-mannosidase from the
      crenarchaeon Sulfolobus solfataricus revealed its ability in de-mannosylating
      glycoproteins.
AB  - alpha-Mannosidases, important enzymes in the N-glycan processing and degradation
      in Eukaryotes, are frequently found in the genome of Bacteria and Archaea in
      which their function is still largely unknown. The alpha-mannosidase from the
      hyperthermophilic Crenarchaeon Sulfolobus solfataricus has been identified and
      purified from cellular extracts and its gene has been cloned and expressed in
      Escherichia coli. The gene, belonging to retaining GH38 mannosidases of the
      carbohydrate active enzyme classification, is abundantly expressed in this
      Archaeon. The purified alpha-mannosidase activity depends on a single Zn(2+) ion
      per subunit is inhibited by swainsonine with an IC(50) of 0.2 mM. The molecular
      characterization of the native and recombinant enzyme, named Ssalpha-man, showed
      that it is highly specific for alpha-mannosides and alpha(1,2), alpha(1,3), and
      alpha(1,6)-D-mannobioses. In addition, the enzyme is able to demannosylate
      Man(3)GlcNAc(2) and Man(7)GlcNAc(2) oligosaccharides commonly found in N
      glycosylated proteins. More interestingly, Ssalpha-man removes mannose residues
      from the glycosidic moiety of the bovine pancreatic ribonuclease B, suggesting
      that it could process mannosylated proteins also in vivo. This is the first
      evidence that archaeal glycosidases are involved in the direct modification of
      glycoproteins.

PMID- 20696205
TI  - Most purported antibodies to the human granulocyte colony-stimulating factor
      receptor are not specific.
AB  - OBJECTIVE: Antibodies to human granulocyte colony-stimulating factor receptor
      (HuG-CSFR) are widely available and have been used in numerous studies to
      evaluate the expression of this protein on normal and malignant cells of
      hematopoietic and nonhematopoietic origin. Spurred by recent studies that
      demonstrated that two commonly used antibodies against the erythropoietin and
      thrombopoietin receptors can in fact bind to completely unrelated and more
      broadly expressed proteins, we screened 27 commercially available monoclonal and
      polyclonal antibodies with claimed specificity to HuG-CSFR to determine if they
      are specific to this receptor. MATERIALS AND METHODS: Antibodies were evaluated
      by Western blotting, flow cytometry, and immunohistochemistry using 293T cells
      engineered to overexpress HuG-CSFR protein, immortalized human hematopoietic cell
      lines expressing endogenous G-CSFR, and purified human neutrophils. RESULTS: Only
      two monoclonal antibodies and one polyclonal antibody could be employed using
      defined Western blotting or flow cytometry protocols to detect G-CSFR protein in
      cell lysates or on the surface of cells that express G-CSFR messenger RNA with no
      binding to cells that did not express the gene. None of the antibodies were
      suitable for immunohistochemistry. Competitive inhibition with soluble G-CSFR
      extracellular domain and small inhibitory RNA-mediated knock-down of G-CSFR
      messenger RNA further demonstrated the limited specificity of these antibodies
      for HuG-CSFR expressed on the cell surface. CONCLUSIONS: Most commercially
      available anti-HuG-CSFR antibodies do not bind specifically to this protein.
      These studies highlight the need for investigators to validate antibodies in
      their own systems to avoid the inadvertent use of nonspecifically binding
      antibodies that could lead, as exemplified in this case with a hematopoietic
      growth factor receptor, to erroneous conclusions about protein expression.

PMID- 20696206
TI  - Role of a novel zebrafish nup98 during embryonic development.
AB  - OBJECTIVE: The nucleoporin NUP98 is a component of the nuclear pore complex that
      regulates nucleocytoplasmic trafficking. It has been characterized in acute
      myeloid leukemia as a fusion partner during chromosomal translocation. In this
      study, we identified a zebrafish nup98 gene and examined its role in embryonic
      development. MATERIALS AND METHODS: Two expressed sequence tags with translated
      sequences homologous to human NUP98 were identified. The gene was cloned by
      polymerase chain reaction from complementary DNA of zebrafish embryos. Cellular
      functions of zebrafish NUP98 were investigated in HeLa cells. nup98 expression
      and developmental functions in zebrafish embryos were investigated by whole-mount
      in situ hybridization and morpholino knockdown. RESULTS: Protein sequence of
      zebrafish nup98 shared 65% identity with its human homolog. Ectopic expression of
      zebrafish nup98 rescued the defective messenger RNA export due to human NUP98
      knockdown in HeLa cells. In zebrafish embryos, nup98 was expressed diffusely in
      eyes and the developing brain since 18 hours postfertilization. Knockdown of
      nup98 with morpholino upregulated pu.1 expression by 39% +/- 15% (p = 0.0153) and
      scl expression by 36% +/- 7.6% (p = 0.0017). Expression of genes associated with
      erythropoiesis was unchanged. The morphants also developed intracranial
      hemorrhage at 48 hours postfertilization due to defective blood vessel
      development. CONCLUSIONS: A novel zebrafish nup98 was identified and it serves a
      role in nucleocytoplasmic trafficking similar to human NUP98. During development,
      it modulates hematopoietic stem cell and early myeloid development and maintains
      the integrity of cranial vasculature in the developing central nervous system.

PMID- 20696207
TI  - Potent synergistic interaction between the Nampt inhibitor APO866 and the
      apoptosis activator TRAIL in human leukemia cells.
AB  - OBJECTIVE: The nicotinamide phosphoribosyltransferase (Nampt) inhibitor APO866
      depletes intracellular nicotinamide adenine dinucleotide (NAD(+)) and shows
      promising anticancer activity in preclinical studies. Tumor necrosis factor
      related apoptosis-inducing ligand (TRAIL) binds to plasma membrane receptors DR4
      and DR5 and induces apoptosis via caspase-8 and -10. Here we have explored the
      interaction between APO866 and TRAIL in leukemia cell lines and in primary B-cell
      chronic lymphocytic leukemia cells. MATERIALS AND METHODS: Cells were treated
      with APO866, TRAIL, or their combination. Viability and mitochondrial
      transmembrane potential (DeltaPsi(m)) were determined by cell staining with
      propidium iodide and tetramethylrhodamine ethyl ester, respectively, and flow
      cytometry. Nampt and gamma-tubulin levels, as well as caspase-3 cleavage were
      detected by immunoblotting. DR4 and DR5 expression were assessed by
      immunostaining and flow cytometry. Caspases were inhibited with zVAD-FMK and
      zDEVD-FMK; autophagy with 3-methyladenine, LY294002, and wortmannin.
      Intracellular NAD(+) and adenosine triphosphate (ATP) were measured by cycling
      assays and high-performance liquid chromatography (HPLC), respectively. RESULTS:
      APO866 induced NAD(+) depletion, DeltaPsi(m) dissipation, and ATP shortage in
      leukemia cells, thereby leading to autophagic cell death. TRAIL induced caspase
      dependent apoptosis. TRAIL addition to APO866 synergistically increased its
      activity in leukemia cells by enhancing NAD(+) depletion, DeltaPsi(m)
      dissipation, and ATP shortage. No DR5 upregulation at the cell surface in
      response to APO866 was observed. Remarkably, in healthy leukocytes APO866 and
      TRAIL were poorly active and failed to show any cooperation. CONCLUSIONS:
      Activation of the extrinsic apoptotic cascade with TRAIL selectively amplifies
      the sequelae of Nampt inhibition in leukemia cells, and appears as a promising
      strategy to enhance APO866 activity in hematological malignancies.

PMID- 20696209
TI  - What controls network reciprocity in the Prisoner's Dilemma game?
AB  - The evolutionary Prisoner's Dilemma game in structured networks has been studied
      extensively to understand network reciprocity. However, in some cases results of
      these studies cannot be compared because not only the network structures but also
      the network parameters, rules for updating strategies, and update dynamics differ
      among them. In this study, we investigated the effect of experimental conditions
      by conducting a series of systematic factorial experiments. We found that those
      experimental assumptions are significantly important in network reciprocity,
      although we confirmed that network reciprocity can be basically explained by the
      average degree of the network (Nowak, 2006; Ohtsuki et al., 2006).

PMID- 20696208
TI  - Establishment of an erythroid cell line from primary CD36+ erythroid progenitor
      cells.
AB  - OBJECTIVE: Most continuous cell lines with erythroid characteristics are derived
      from patients with myelogenous leukemia or erythroleukemia. Among them, a few
      cell lines have been reported to be positive for CD36. We tried to establish a
      continuous erythroid cell line from the primary CD36(+) erythroid progenitor
      cells (EPCs) by the lentivirus-mediated gene transduction system. MATERIALS AND
      METHODS: A lentiviral vector carrying SV40T, hTERT, or the human papillomavirus
      type 16 (HPV16) E6 and E7 (E6/E7) viral oncogenes, was introduced into CD36(+)
      EPCs, singularly or combined. Transformed cells were characterized in terms of
      histology, phenotype, karyotype, and gene expression profile. RESULTS: The
      lentiviral vector carrying HPV16 E6/E7 genes successfully transformed CD36(+)
      EPCs, creating a continuous cell line, CD36E. Immunophenotype analysis revealed
      that the CD36E cells had characteristics of erythroid progenitors, among which
      about 27% of the cell population produced hemoglobin. Colony-forming cell assay
      demonstrated that the CD36E cells were capable of forming erythroid colonies.
      Using cytokines or chemical agents, attempts were made to induce differentiation
      of the CD36E cells but were ineffective, indicating the irreversible erythroid
      lineage commitment of the cells. The gene expression profile of the CD36E cells
      displayed a marked difference from that of the CD36(+) EPCs. CONCLUSIONS: The
      continuous CD36E cell line is an erythroid progenitor cell line possessing the
      ability to produce hemoglobin. The CD36E cell line would be an excellent tool for
      applied research involving erythroid lineage cells and comparative studies with
      primary CD36(+) EPCs.

PMID- 20696210
TI  - The axonal guidance factor netrin-1 as a potential modulator of swine follicular
      function.
AB  - This study was aimed to improve knowledge about swine ovarian follicular
      function, paying attention to angiogenesis, since new vessel growth is a
      fundamental event in ovarian function. In particular, we investigated a potential
      involvement of netrin-1, a protein known as a guidance axon factor. Firstly, we
      studied the expression and immunolocalization of netrin-1 in swine ovarian
      follicle and its effect on cultured swine granulosa cell viability and
      steroidogenesis. Furthermore, aortic endothelial cells were employed to verify a
      possible netrin-1 effect on angiogenesis. Our data demonstrate the expression and
      the presence of netrin-1 in swine follicular fluid; in addition, it was shown
      that netrin-1 inhibits granulosa cell viability and estradiol 17beta levels while
      it stimulates progesterone production. Netrin-1 also inhibits aortic endothelial
      cell growth in the angiogenesis bioassay. This effect appears to be mediated by
      inhibiting vascular endothelial growth factor and stimulating nitric oxide.
      Therefore, we hypothesize that netrin-1 could be important for follicular
      function in the swine.

PMID- 20696211
TI  - Postnatal fluoxetine treatment affects the development of serotonergic neurons in
      rats.
AB  - The goal of the present study was to investigate morphological changes in the
      serotonergic neurons/terminals in the dorsal (DR) and median (MnR) raphe nuclei
      and on the hippocampal dentate gyrus (DG) in neonatal rats treated from the 1st
      to the 21st postnatal day with fluoxetine (10 mg/kg sc, daily) or drug vehicle
      (0.9% saline 1 ml/kg). The results show that postnatal chronic treatment with
      fluoxetine promoted: (1) a smaller body weight increase during the pre-weaning
      period; (2) smaller number of 5-HT neurons in the DR; (3) smaller 5-HT neuronal
      cell bodies (area, perimeter and diameter) in the DR and the MnR and (4)
      diminished serotonergic terminals in the DG. These data suggest that the
      development of the serotonergic system was impaired and that early exposure to
      fluoxetine damaged the morphology of 5-HT neurons in young adult rats. While
      these findings are consistent with other work, more studies are needed to better
      clarify the effects of postnatal chronic treatment with fluoxetine on the
      serotonergic system and, consequently, on the functions modulated by serotonin.

PMID- 20696212
TI  - Insulin regulates Presenilin 1 localization via PI3K/Akt signaling.
AB  - Recently, insulin signaling has been highlighted in the pathology of Alzheimer's
      disease (AD). Although the association between insulin signaling and Tau
      pathology has been investigated in several studies, the interaction between
      insulin signaling and Presenilin 1 (PS1), a key molecule of amyloid beta (Abeta)
      pathology, has not been elucidated so far. In this study, we demonstrated that
      insulin inhibited PS1 phosphorylation at serine residues (serine 353, 357) via
      phosphatidylinositol 3-kinase (PI3K)/Akt signal pathway and strengthened the
      trimeric complex of PS1/N-cadherin/beta-catenin, consequently relocalizing PS1 to
      the cell surface. Since our recent report suggests that PS1/N-cadherin/beta
      catenin complex regulates Abeta production, it is likely that insulin signaling
      affects Abeta pathology by regulating PS1 localization.

PMID- 20696213
TI  - Modanifil activates the histaminergic system through the orexinergic neurons.
AB  - Modafinil is a drug used to treat hypersomnolence of narcolepsy. We previously
      reported that modafinil increases hypothalamic histamine release in rats but did
      not increase locomotor activity in histamine-depleted mice, suggesting that
      modafinil-induced locomotor activity involves the histaminergic system. Modafinil
      is also thought to express its effect through the orexinergic neurons, and orexin
      increases hypothalamic histamine release. These findings led us to investigate
      whether modafinil activates the histaminergic system via the orexinergic system.
      In the present study, we performed in vivo microdialysis and c-Fos
      immunohistochemistry to investigate whether the orexinergic system mediates the
      activation of the histaminergic system by modafinil using orexin neuron-deficient
      mice. Two hours after the injection, modafinil (150 mg/kg) caused a significant
      increase of histamine release compared to the basal release in wild type mice.
      However, modafinil had no effect on the histamine release in orexin neuron
      deficient mice. By immunohistochemical study, we found that there was no neuronal
      activation in the tuberomammillary nucleus where the cell bodies of the
      histaminergic neurons exclusively exist in orexin neuron-deficient mice. These
      findings indicate that modafinil-induced increment of histamine release requires
      intact orexinergic neurons.

PMID- 20696214
TI  - A transcriptional regulatory element critical for CHRNB4 promoter activity in
      vivo.
AB  - Genome-wide association studies have underscored the importance of the clustered
      neuronal nicotinic acetylcholine receptor (nAChR) subunit genes with respect to
      nicotine dependence as well as lung cancer susceptibility. CHRNB4, which encodes
      the nAChR beta4 subunit, plays a major role in the molecular mechanisms that
      govern nicotine withdrawal. Thus, elucidating how expression of the beta4 gene is
      regulated is critical for understanding the pathophysiology of nicotine
      addiction. We previously identified a CA box regulatory element, (5'-CCACCCCT-3')
      critical for beta4 promoter activity in vitro. We further demonstrated that a 2.3
      kb fragment of the beta4 promoter region containing the 5'-CCACCCCT-3' regulatory
      element in the beta4 gene promoter (CA box) is capable of directing cell-type
      specific expression of a reporter gene to a myriad of brain regions that
      endogenously express the beta4 gene. To test the hypothesis that the CA box is
      critical for beta4 promoter activity in vivo, transgenic animals expressing a
      mutant form of the beta4 promoter were generated. Reporter gene expression was
      not detected in any tissue or cell type at embryonic day 18.5 (ED 18.5).
      Similarly, we observed drastically reduced reporter gene expression at postnatal
      day 30 (PD30) when compared to wild type (WT) transgenic animals. Finally, we
      demonstrated that CA box mutation results in decreased interaction of the
      transcription factor Sp1 with the mutant beta4 promoter. Taken together these
      results demonstrate that the CA box is critical for beta4 promoter activity in
      vivo.

PMID- 20696215
TI  - Integration of CO2 and odorant signals in the mouse olfactory bulb.
AB  - Carbon dioxide (CO(2)) is an important environmental cue for many animal species.
      In both vertebrates and invertebrates, CO(2) is detected by a specialized subset
      of olfactory sensory neurons (OSNs) and mediates several stereotypical behaviors.
      It remains unknown how CO(2) cues are integrated with other olfactory signals in
      the mammalian olfactory bulb, the first stage of central olfactory processing. By
      recording from the mouse olfactory bulb in vivo, we found that CO(2)-activating
      neurons also respond selectively to odorants, many of which are putative mouse
      pheromones and natural odorants. In addition, many odorant-responsive bulbar
      neurons are inhibited by CO(2). For a substantial number of CO(2)-activating
      neurons, binary mixtures of CO(2) and a specific odorant produce responses that
      are distinct from those evoked by either CO(2) or the odorant alone. In addition,
      for a substantial number of CO(2)-inhibiting neurons, CO(2) addition can
      completely block the action potential firing of the cells to the odorants. These
      results indicate strong interaction between CO(2) signals and odorant signals in
      the olfactory bulb, suggesting important roles for the integration of these two
      signals in CO(2)-mediated behavioral responses.

PMID- 20696216
TI  - Effects of the probiotic Bifidobacterium infantis in the maternal separation
      model of depression.
AB  - The concept that intestinal microbial composition not only affects the health of
      the gut, but also influences centrally-mediated systems involved in mood, is
      supported by a growing body of literature. Despite the emergent interest in brain
      gut communication and its possible role in the pathogenesis of psychiatric
      disorders such as depression, particularly subtypes with accompanying
      gastrointestinal (GI) symptoms, there are few studies dedicated to the search for
      therapeutic solutions that address both central and peripheral facets of these
      illnesses. This study aims to assess the potential benefits of the probiotic
      Bifidobacterium infantis in the rat maternal separation (MS) model, a paradigm
      that has proven to be of value in the study of stress-related GI and mood
      disorders. MS adult rat offsprings were chronically treated with bifidobacteria
      or citalopram and subjected to the forced swim test (FST) to assess motivational
      state. Cytokine concentrations in stimulated whole blood samples, monoamine
      levels in the brain, and central and peripheral hypothalamic-pituitary-adrenal
      (HPA) axis measures were also analysed. MS reduced swim behavior and increased
      immobility in the FST, decreased noradrenaline (NA) content in the brain, and
      enhanced peripheral interleukin (IL)-6 release and amygdala corticotrophin
      releasing factor mRNA levels. Probiotic treatment resulted in normalization of
      the immune response, reversal of behavioral deficits, and restoration of basal NA
      concentrations in the brainstem. These findings point to a more influential role
      for bifidobacteria in neural function, and suggest that probiotics may have
      broader therapeutic applications than previously considered.

PMID- 20696217
TI  - Passive tactile recognition of geometrical shape in humans: An fMRI study.
AB  - Tactile shape discrimination involves frontal other than somatosensory cortex
      (Palva et al., 2005 [48]), but it is unclear if this frontal activity is related
      to exploratory concomitants. In this study, we investigated topographical details
      of prefrontal, premotor, and parietal areas during passive tactile recognition of
      2D geometrical shapes in conditions avoiding exploratory movements. Functional
      magnetic resonance imaging (fMRI) was performed while the same wooden 2D
      geometrical shapes were blindly pressed on subjects' passive right palm in three
      conditions. In the RAW condition, shapes were pressed while subjects were asked
      to attend to the stimuli but were not trained to recognize them. After a brief
      training, in the SHAPE condition subjects were asked to covertly recognize
      shapes. In the RECOGNITION condition, they were asked to overtly recognize
      shapes, using response buttons with their opposite hand. Results showed that
      somatosensory cortex including contralateral SII, contralateral SI, and left
      insula was active in all conditions, confirming its importance in processing
      tactile shapes. In the RAW vs. SHAPE contrast, bilateral posterior parietal,
      insular, premotor, prefrontal, and (left) Broca's areas were more active in the
      latter. In the RECOGNITION, activation of (left) Broca's area correlated with
      correct responses. These results suggest that, even without exploratory
      movements, passive recognition of tactile geometrical shapes involves prefrontal
      and premotor as well as somatosensory regions. In this framework, Broca's area
      might be involved in a successful selection and/or execution of the correct
      responses.

PMID- 20696218
TI  - What experimental experience affects dogs' comprehension of human communicative
      actions?
AB  - Studies of dogs report that individuals reliably respond to the goal-directed
      communicative actions (e.g., pointing) of human experimenters. All of these
      studies use some version of a multi-trial approach, thereby allowing for the
      possibility of rapid learning within an experimental session. The experiments
      reported here ask whether dogs can respond correctly to a communicative action
      based on only a single presentation, thereby eliminating the possibility of
      learning within the experimental context. We tested 173 dogs. For each dog
      reaching our test criteria, we used a single presentation of six different goal
      directed actions within a session, asking whether they correctly follow to a
      target goal (container with concealed food) a (1) distal hand point, (2) step
      toward one container, (3) hand point to one container followed by step toward the
      other, (4) step toward one container and point to the other, (5) distal foot
      point with the experimenter's hands free, and (6) distal foot point with the
      experimenter's hands occupied. Given only a single presentation, dogs selected
      the correct container when the experimenter hand pointed, foot pointed with hands
      occupied, or stepped closer to the target container, but failed on the other
      actions, despite using the same method. The fact that dogs correctly followed
      foot pointing with hands occupied, but not hands free, suggests that they are
      sensitive to environmental constraints, and use this information to infer
      rational, goal-directed action. We discuss these results in light of the role of
      experience in recognizing communicative gestures, as well as the significance of
      coding criteria for studies of canine competence.

PMID- 20696219
TI  - Pivotal role of Twist in skeletal biology and pathology.
AB  - Basic Helix-loop-Helix (bHLH) factors play important roles in development and
      disease. Recent functional and genetic analyses revealed that the bHLH factor
      Twist1 is a critical modulator of mesenchymal cell fate during skeletal
      development. Specifically, studies in mice and humans showed that Twist1 controls
      mesenchymal stem cell differentiation into chondrocytes, osteoblasts or
      adipocytes via direct and indirect mechanisms. In a physiological context, Twist1
      targets several molecular mechanisms to induce positive or negative effects on
      osteoblastic cell growth, differentiation and survival. In a pathological
      context, Twist1 loss-of-function mutations induce premature cranial suture fusion
      (craniosynostosis) in the Saethre-Chotzen syndrome. In this syndrome, expansion
      of cranial osteogenesis at the suture level results from alterations in the
      balance between osteoprogenitor cell proliferation, differentiation and
      apoptosis. These studies provide mechanisms by which Twist1 plays a pivotal role
      in skeletal cell fate in normal and pathologic conditions, which may offer
      therapeutic perspectives in conditions where mesenchymal cell behaviour is
      compromised.

PMID- 20696220
TI  - Interactions between atropine and etomidate in cortical and spinal networks
      during cholinergic crisis.
AB  - General anaesthesia is an important measure in the treatment of patients
      suffering from organophosphorus intoxication. The intravenous anaesthetic
      etomidate seems to be well suited for this purpose because of its stable
      haemodynamics. Here we raise the question whether the anaesthetic properties of
      etomidate are altered by cholinergic overstimulation and by the cholinergic
      antagonist atropine. As the neocortex and spinal cord mediate unconsciousness and
      immobility, organotypic cultures from these regions were used for pharmacological
      in vitro studies. The effects of etomidate on spontaneous action potential
      activity were assessed by extracellular action potential recordings under basal
      cholinergic tone, in the presence of acetylcholine, and in the additional
      presence of atropine. Etomidate (1MUM) depressed neuronal activity in cortical
      slices by 47.5+/-6.9%, but only by 24.9+/-16.7% in the presence of acetylcholine.
      If atropine (10nM) was given in addition, the depression by etomidate was
      restored (53.4+/-4.2%). Similar results were obtained using cultured slices from
      the spinal cord. In summary, cholinergic overstimulation decreased the ability of
      etomidate to depress neuronal activity in neocortex and spinal cord. Atropine
      reversed this decrease. Hence, etomidate is potentially applicable for induction
      of anaesthesia in patients suffering from severe cholinergic crisis,
      preconditioned that atropine is co-applied.

PMID- 20696221
TI  - Disposition and biotransformation of 14C-Benzo(a)pyrene in a pig ear skin model:
      ex vivo and in vitro approaches.
AB  - Biotransformation of chemicals by the skin is a critical determinant of systemic
      exposure in humans following dermal absorption. Pig ear skin potentially
      represents a valuable alternative model since it closely resembles to human skin.
      We developed an ex vivo pig ear skin system which absorption, diffusion and
      metabolic capabilities were investigated using benzo(a)pyrene [B(a)P] as a model
      molecule. The potential of the ex vivo pig ear skin model to biotransform
      xenobiotics was compared with metabolic data obtained using dermal and hepatic
      microsomes from human and pig. (14)C-B(a)P [50-800 nmol] was applied on the
      surface of skin models. The diffusion and the production of B(a)P metabolites
      were quantified by radio-HPLC, LC-MS/MS and NMR. B(a)P was extensively
      metabolized by pig ear skin explants, the major metabolites being B(a)P
      glucuronide and sulfate conjugates. B(a)P-OHs, B(a)P-diols, B(a)P-catechols and
      B(a)P-diones were also identified. In the pig ear skin model developed, skin
      diffusion was maintained over 72 h and both phase I and phase II activities were
      expressed, with the formation of similar metabolites as produced in incubations
      with liver and skin microsomal fractions. This ex vivo model, which combines a
      functional skin barrier and active biotransformation capabilities, appears to
      represent a valuable alternative tool in transdermal exposure studies.

PMID- 20696222
TI  - Protective effect of BMP-7 against aristolochic acid-induced renal tubular
      epithelial cell injury.
AB  - Aristolochic acid nephropathy (AAN) is regarded as a kind of rapidly progressive
      renal fibrosis caused by the ingestion of herbal remedies containing aristolochic
      acid (AA). Recent studies showed that bone morphogenetic protein-7 (BMP-7) exerts
      beneficial effects on acute and chronic kidney injuries induced by different
      pathological conditions. We examined whether BMP-7 protects human renal tubular
      epithelial cells (HK-2) against AA-induced injury in vitro. HK-2 cells were
      cultured with different concentrations of AA and BMP-7 for 48h. Cell viability
      was determined by Cell Counting Kit-8 assay and lactate dehydrogenase (LDH)
      release. The apoptosis rate and the activity of caspase 3 protease were also
      examined. Epithelial-to-mesenchymal transition (EMT) was determined by cell
      morphology, E-cadherin and alpha-smooth muscle actin (alpha-SMA) protein
      expression, and TGF-beta(1) and collagen III secretion. Additionally, the effect
      of anti-TGF-beta1 antibody on AA-induced EMT was assessed. Our results indicated
      that BMP-7 significantly increased cell proliferation, decreased apoptosis rate
      and attenuated activation of caspase-3, resulting in the protection of HK-2 cells
      from AA-induced cytotoxicity. In addition, studies on EMT revealed that BMP-7
      could inhibit AA-induced myofibroblast phenotype and restored the epithelial
      morphology in a dose-dependent manner. It was partially through reducing the
      activation of a myofibroblast phenotype and production TGF-beta1. Treatment with
      neutralizing anti-TGF-beta1 antibody also blocked AA-induced EMT and collagen III
      secretion. Together, these observations strongly suggest that BMP-7 is a potent
      inhibitor of AA-induced renal tubular epithelial cell injury and might be a
      promising agent for aristolochic acid-induced kidney damage.

PMID- 20696223
TI  - High-throughput cocrystal slurry screening by use of in situ Raman microscopy and
      multi-well plate.
AB  - Cocrystal has attracted much attention in order to improve poor physicochemical
      properties, since cocrystal former crystallize with the ionic drugs as well as
      nonionic drugs. Cocrystal screening was usually conducted by crystallization,
      slurry and co-grinding techniques, however sensitivity, cost and time for
      screening were limited because of issues such as dissociation of cocrystal during
      crystallization and cost and time required for slurry and co-grinding methods. To
      overcome these issues, novel high-throughput cocrystal slurry screening was
      developed by using in situ Raman microscope and a multi-well plate. Cocrystal
      screening of indomethacin was conducted with 46 cocrystal formers and potential
      cocrystals were prepared on a large scale for the characterization with powder X
      ray diffractometry, thermal analysis, and Raman microscopy and (1)H NMR
      spectroscopy. Compared with the characterization of scale-up cocrystals, the
      cocrystal screening indicated that indomethacin structured novel cocrystals with
      D/L-mandelic acid, nicotinamide, lactamide and benzamide which was not obtained
      in the screening with crystallization technique previously reported. In addition,
      the screening provided not only information of cocrystal formation within a day
      but also information of equilibrium of cocrystal formation and polymorphic
      transformation in one screening. Information obtained in this screening allows
      effective solid form selection by saving cost and time for the development.

PMID- 20696224
TI  - Design and synthesis of 99mTc-citro-folate for use as a tumor-targeted
      radiopharmaceutical.
AB  - Folate conjugates exhibit high affinity for folate receptor (FR) positive cells
      and tissues, such as those in tumors, making them attractive candidates and of
      interest in diagnostic tumor imaging. The aim of study was to synthesize a novel
      radiopharmaceutical based folate conjugate, (99m)Tc-citro-folate, and to evaluate
      its efficiency as a targeted agent for imaging tumors that over express FR. TLC,
      HPLC (1)H NMR and LC-MS/MS methods were used to check and confirm the synthesized
      citro-folate. Citro-folate was labeled with Tc-99m with high labeling efficiency
      (97+/-1.0%). Biodistribution of the radiolabeled conjugate (99m)Tc-citro-folate
      was investigated in vivo using two groups of rats: FR saturated and unsaturated.
      These experiments showed high uptake of (99m)Tc-citro-folate in FR rich tissues
      and demonstrated its sensitivity and specificity in imaging ovary and uterus.
      Based on the demonstrated good radiolabeling and biodistribution properties, the
      compound (99m)Tc-citro-folate may potentially be used as a radiopharmaceutical
      agent for imaging the FR-positive tumors.

PMID- 20696225
TI  - Simultaneous delivery of Nifedipine and Metoprolol tartarate using sandwiched
      osmotic pump tablet system.
AB  - The sandwiched osmotic tablet system that could deliver Nifedipine and Metoprolol
      tartarate simultaneously for extended period of time was developed in order to
      reduce the problems associated with multidrug therapy of hypertension. This
      system composed of a middle push layer and attached drug layers of Nifedipine and
      Metoprolol. The advantage of the sandwiched osmotic tablet system over the
      commercialized push-pull osmotic tablet system is its simplicity of preparation,
      as the surface identification was avoided. Polyethylene oxide 600,000 and
      8,000,000 g/mole were used as thickening agent of drug layer and the expandable
      hydrogel of push layer, respectively. It has been observed that amount of
      polyethylene oxide (PEO) and KCL of the drug and push layer had profound
      influence on Nifedipine and Metoprolol release. Further, the release of drugs was
      optimized by the size of the delivery orifice, level of plasticizer and membrane
      thickness. The optimal osmotic pump tablet was found to deliver both drugs at a
      rate of approximately zero order for up to 16 h independent of pH and agitational
      intensity, but dependent on the osmotic pressure of the release media. The
      formulations were found to be stable after 3 months of accelerated stability
      studies. Prediction of steady-state levels showed the plasma concentrations of
      Nifedipine and Metoprolol to be within the desired range. Further sandwiched
      system had a good sustained effect in comparison with the conventional product.
      Hence the prototype design of the system could be applied to other combinations
      of drugs used for cardiovascular diseases, diabetes, etc.

PMID- 20696227
TI  - Poloxamer 407 microspheres for orotransmucosal drug delivery. Part I:
      formulation, manufacturing and characterization.
AB  - The two-part article aimed to investigate poloxamer 407-based microspheres as a
      novel platform for enhancing and controlling the delivery of atenolol across the
      oromucosal tissue. In the Part I of the work, atenolol-loaded poloxamers 407
      microparticles were prepared by the solvent free spray congealing technology.
      This approach was feasible upon the high viscosity of the systems allowing for
      high loaded (20% w/w) non-aggregated microspheres. Several formulations were
      studied and the results demonstrated that the drug release patterns, solubility
      data, mucoadhesion to buccal tissue and gelling properties in saliva could be
      modified by adding different amount of an amphiphilic polymer-lipid excipient
      (Gelucire((r)) 50/13) to poloxamer 407. Particularly, microspheres based only on
      poloxamer 407 exhibited very high solubility, mucoadhesive strength and gelling
      behaviour. To assess their potential as matrix for buccal application, the
      gelling property and the drug release from tablets obtained from direct
      compression of the microparticles were further evaluated. The microspheres were
      then characterized by differential scanning calorimetry, X-ray powder diffraction
      and Fourier transform-infrared spectra analysis. No solid state modifications and
      chemical interactions were detectable in the microspheres after manufacturing and
      during storage, suggesting their stability and use as orotransmucosal delivery
      systems.

PMID- 20696226
TI  - A phospholipid-apolipoprotein A-I nanoparticle containing amphotericin B as a
      drug delivery platform with cell membrane protective properties.
AB  - Amphotericin B (AMB), a potent antifungal agent, has been employed as an
      inhalable therapy for pulmonary fungal infections. We recently described a novel
      nano-sized delivery vehicle composed of phospholipid (PL) and apolipoprotein A-I,
      NanoDisk (ND), to which we added AMB as a payload (ND-AMB). The goal of the
      present study was to evaluate whether ND-AMB, compared to other formulations,
      preserves lung cell integrity in vitro, as AMB can be toxic to mammalian cells
      and reduce lung function when inhaled. Epithelial integrity was assessed by
      measuring K(+) ion flux across a model airway epithelium, Calu-3 cells. In this
      assay ND-AMB was at least 8-fold less disruptive than AMB/deoxycholate (DOC).
      Cell viability studies confirmed this observation. Unexpectedly, the ND vehicle
      restored the integrity of a membrane compromised by prior exposure to AMB. An
      alternative formulation of ND-AMB containing a high load of AMB per ND was not
      protective, suggesting that ND with a low ratio of AMB to PL can sequester
      additional AMB from membranes. ND-AMB also protected HepG2 cells from the
      cytotoxicity of AMB, as determined by cellular viability and lactate
      dehydrogenase (LDH) levels. This study suggests that ND-AMB may be safe for
      administration via inhalation and reveals a unique activity whereby ND-AMB
      protects lung epithelial membranes from AMB toxicity.

PMID- 20696228
TI  - Anti-CD8 conjugated nanoparticles to target mammalian cells expressing CD8.
AB  - This work aimed at the development of targeted drug delivery systems using
      nanoparticles fused with antibodies. The antibody anti-human CD8 was coupled onto
      PLGA nanoparticles, and the ability of these particles to specifically target
      cells expressing CD8 was studied. The obtained particles were found to be of
      spherical shape exhibiting a size between 350 and 600 nm. In vitro experiments
      with different cellular cultures (TE671, CHO and HEK293) using unmodified
      nanoparticles containing rhodamine have shown that particles were present on
      their surface within 48 h of incubation. In vitro tests using anti-CD8 conjugated
      nanoparticles in CHO cell cultures indicated that all transfected cells which
      express CD8 show these particles on their surface within 1h of incubation. These
      results demonstrated that, in a shorter time, the produced particles can target
      cells expressing CD8 on their surface which offers the ability to reduce drug
      side effects. The antibody-coupled nanoparticles represent a promising approach
      to improve the efficacy of active targeting for lymphoblastic leukaemia therapy.

PMID- 20696229
TI  - Ossicular motion related to middle ear transmission delay in gerbil.
AB  - The middle ear transmits sound efficiently from the air in the ear canal (EC) to
      the fluid filled cochlea. In gerbil, middle ear transmission produces a constant
      pressure gain between the EC and the cochlea of ~25 dB from 2 to 40 kHz, and a
      delay-like phase corresponding to a ~25-30 MUs delay. The mechanisms by which the
      air-born signal is collected and delivered to the cochlea are not thoroughly
      understood, and the source of the delay is controversial. We investigated these
      issues by observing ossicular motion along a single line of sight, roughly
      parallel to the EC and perpendicular to the stapes footplate. Measurements were
      made at the umbo, the long process of the manubrium, across the malleus-incus
      joint, at the long process of the incus, and the stapes head. While the overall
      delay between EC pressure and stapes velocity was fairly constant with frequency,
      subcomponents of the delay were frequency dependent. Up to ~17 kHz, most of the
      overall delay was between the EC and umbo with a much smaller contribution along
      the ossicles, whereas in the range from ~17 to 30 kHz, more of the overall delay
      was along the ossicles.

PMID- 20696230
TI  - Noise-induced hearing loss alters the temporal dynamics of auditory-nerve
      responses.
AB  - Auditory-nerve fibers demonstrate dynamic response properties in that they adapt
      to rapid changes in sound level, both at the onset and offset of a sound. These
      dynamic response properties affect temporal coding of stimulus modulations that
      are perceptually relevant for many sounds such as speech and music. Temporal
      dynamics have been well characterized in auditory-nerve fibers from normal
      hearing animals, but little is known about the effects of sensorineural hearing
      loss on these dynamics. This study examined the effects of noise-induced hearing
      loss on the temporal dynamics in auditory-nerve fiber responses from anesthetized
      chinchillas. Post-stimulus-time histograms were computed from responses to 50-ms
      tones presented at characteristic frequency and 30 dB above fiber threshold.
      Several response metrics related to temporal dynamics were computed from post
      stimulus-time histograms and were compared between normal-hearing and noise
      exposed animals. Results indicate that noise-exposed auditory-nerve fibers show
      significantly reduced response latency, increased onset response and percent
      adaptation, faster adaptation after onset, and slower recovery after offset. The
      decrease in response latency only occurred in noise-exposed fibers with
      significantly reduced frequency selectivity. These changes in temporal dynamics
      have important implications for temporal envelope coding in hearing-impaired
      ears, as well as for the design of dynamic compression algorithms for hearing
      aids.

PMID- 20696231
TI  - Activation of the nuclear receptor PPARgamma by metabolites isolated from sage
      (Salvia officinalis L.).
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Salvia officinalis has been used as a traditional
      remedy against diabetes in many countries and its glucose-lowering effects have
      been demonstrated in animal studies. The active compounds and their possible mode
      of action are still unknown although it has been suggested that diterpenes may be
      responsible for the anti-diabetic effect of Salvia officinalis. AIM OF THE STUDY:
      To investigate whether the reported anti-diabetic effects of Salvia officinalis
      are related to activation of the nuclear receptor peroxisome proliferator
      activated receptor (PPAR)gamma and to identify the bioactive constituents.
      MATERIALS AND METHODS: From a dichloromethane extract of Salvia officinalis able
      to activate PPARgamma several major metabolites were isolated by chromatographic
      techniques. To assess bioactivity of the isolated metabolites a PPARgamma
      transactivation assay was used. RESULTS: Eight diterpenes were isolated and
      identified including a new abietane diterpene being the epirosmanol ester of 12-O
      methyl carnosic acid and 20-hydroxyferruginol, which was isolated from Salvia
      officinalis for the first time, as well as viridiflorol, oleanolic acid, and
      alpha-linolenic acid. 12-O-methyl carnosic acid and alpha-linolenic acid were
      able to significantly activate PPARgamma whereas the remaining metabolites were
      either unable to activate PPARgamma or yielded insignificant activation.
      CONCLUSIONS: Selected metabolites from Salvia officinalis were able to activate
      PPARgamma and hence, the anti-diabetic activity of this plant could in part be
      mediated through this nuclear receptor.

PMID- 20696232
TI  - Abarema cochliacarpos: gastroprotective and ulcer-healing activities.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Abarema cochliacarpos (Gomes) Barneby & Grimes
      (Mimosaceae) is a species--in folk medicine of Lagarto city, Sergipe state,
      northeastern Brazil--reputed to heal gastric ulcer and gastritis. AIM OF THE
      STUDY: Chloroform (CE) and methanolic (ME) extracts as well as ethyl acetate
      fraction (AF), butanolic fraction (AC) and aqueous fraction (AQF) of the
      methanolic extract of Abarema cochliacarpos bark were evaluated against acute
      gastric ulcer. The AC fraction was selected to assess its activity in ulcer
      healing and its gastroprotective effects via mucus and gastric secretion.
      MATERIAL AND METHODS: The gastroprotective action of CE and ME extracts and the
      fractions of the latter were evaluated in a rodent experimental model. The action
      mechanisms, involvements of the antisecretory action and mucus production,
      toxicological and healing activity of the AC (150 mg/kg, p.o.) were evaluated. We
      also used histological analysis (HE and PAS) and immunohistochemical (PCNA, COX
      2, VEGF and HSP-70) assays to evaluate the effects of Abarema cochliacarpos.
      RESULTS: CE (200 and 400 mg/kg, p.o.) and ME (100, 200 and 400 mg/kg, p.o.)
      extracts were able to protect gastric mucosa against absolute ethanol. Respective
      inhibitions produced were: 65.31% and 83.80% by the first; 91.69%, 96.75% and
      99.80% by the second; and 74.24% by the AC fraction. Antisecretory and mucus
      production effects were exhibited by the AC fraction, which also accelerated the
      healing of ulcerated gastric mucosa by stimulating proliferation factors (PCNA)
      and induced healing factors including COX-2, VEGF and HSP-70. CONCLUSION: All
      these results suggest that Abarema cochliacarpos (Gomes) Barneby & Grimes
      presents gastroprotective effects and wound-healing properties.

PMID- 20696233
TI  - Butein suppresses the expression of nuclear factor-kappa B-mediated matrix
      metalloproteinase-9 and vascular endothelial growth factor in prostate cancer
      cells.
AB  - 3,4,2',4'-Tetrahydroxychalcone (butein) has potent anti-inflammatory, anti-cancer
      and anti-fibrogenic effects. However, little is known about the mechanism by
      which butein inhibits metastasis and invasion. This study aimed to investigate
      the effects of butein on the expression of matrix metalloproteinase (MMP-9) and
      vascular endothelial growth factor (VEGF) in human prostate cancer cells. Butein
      in vitro resulted in a moderate inhibition of cell proliferation and viability
      through G(2)/M phase arrest. We also analyzed the effect of butein on the
      activities of nuclear factor-kappa B (NF-kappaB)-regulated MMP-9 and VEGF since
      they are prominently involved in the processes of tumor cell invasion and
      metastasis. Our results in vitro showed that butein attenuates VEGF and MMP-9
      activities via the suppression of NF-kappaB activity. Furthermore, butein
      repressed the expression of VEGF and MMP-9 induced by treatment with tumor
      necrosis factor-alpha and phorbol-12-myristate-13-acetate. Taken together, these
      data suggest that a blockade of NF-kappaB activity by butein inhibits invasion
      and angiogenesis in prostate cancer cells.

PMID- 20696234
TI  - A methyl jasmonate derivative, J-7, induces apoptosis in human hepatocarcinoma
      Hep3B cells in vitro.
AB  - The pro-apoptotic activity of J-7, a synthetic methyl jasmonate derivative, on
      the Hep3B human hepatocarcinoma cell line was investigated. Treatment of Hep3B
      cells with J-7 resulted in growth inhibition and the induction of apoptosis as
      measured by trypan blue-excluding cells, MTT assay, nuclear staining, DNA
      fragmentation, and flow cytometry analysis. The increased apoptotic events in
      Hep3B cells caused by J-7 were associated with the alteration in the ratio of
      Bax/Bcl-2 protein expression. J-7 treatment induced the expression of death
      receptor-related proteins such as death receptor 5, which triggered the
      activation of caspase-8 and the down-regulation of the whole Bid expression. In
      addition, the apoptosis induction by J-7 was correlated with the activation of
      caspase-9 and caspase-3, down-regulation IAP family proteins such as XIAP and
      cIAP-1, and concomitant degradation of poly (ADP-ribose) polymerase. However, the
      cytotoxic and apoptotic effects induced by J-7 were significantly inhibited by z
      DEVD-fmk, a caspase-3 inhibitor, which demonstrates the important role that
      caspase-3 plays in the process. Furthermore, blocking the extracellular signal
      regulated protein kinase and c-Jun N-terminal kinase pathways showed increased
      apoptosis and the activation of caspases in J-7-induced apoptosis. The results
      indicated that J-7 induces the apoptosis of Hep3B cells through a signaling
      cascade of death-receptor-mediated extrinsic as well as mitochondria-mediated
      intrinsic caspase pathways, which are associated with the activation of the
      mitogen-activated protein kinases signal pathway.

PMID- 20696235
TI  - Effects of testosterone on orchiectomy-induced oxidative damage in the rat
      hippocampus.
AB  - The aim of this study was to investigate the morphological changes of the
      hippocampus after orchiectomy and the protective effects of testosterone on these
      changes. Animals were divided into 3 groups. The rats in group I were used for
      sham-orchiectomy. Orchiectomy was performed on the rats in group II. The rats in
      group III were administrated testosterone propionate 0.5mg/kg/day for 30 days
      after the orchiectomy. Some of the hippocampal tissues were used for
      determination of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px)
      enzyme activities, and malondialdehyde (MDA) levels. The remaining hippocampal
      tissue specimens were stained with routine histological methods and examined
      under the light microscope. Additionally, the samples were immunohistochemically
      stained by using avidin-biotin-peroxidase for determination of bax
      immunoreactivity. The SOD and GSH-Px enzyme activities of the hippocampus were
      decreased, and MDA levels were increased in group II rats compared to the sham
      orchiectomy group. In the light microscopic evaluation of the tissue specimens
      from group II, significant increases were detected in the number of picnotic
      cells and in bax immunoreactivity compared to the sham-orchiectomy group.
      However, an increase was observed in activities of SOD and GSH-Px enzymes and a
      decrease of the MDA levels in animals with orchiectomy, but having externally
      administered testosterone. It was determined that the increase of bax
      immunoreactivity and histopathological changes in this group were regressed by
      testosterone. The results of our study revealed that orchiectomy-induced
      oxidative damage and morphological changes in the hippocampal tissue were
      suppressed by testosterone.

PMID- 20696236
TI  - Malondialdehyde-acetaldehyde adduct is the dominant epitope after MDA
      modification of proteins in atherosclerosis.
AB  - Antibodies to malondialdehyde (MDA)-modified macromolecules (adducts) have been
      detected in the serum of patients with atherosclerosis and correlate with the
      progression of this disease. However, the epitope and its formation have not been
      characterized. Studies have shown that excess MDA can be degraded to
      acetaldehyde, which combines with proteins to from a stable dihydropyridine
      adduct. To investigate, mice were immunized with MDA adducts in the absence of
      adjuvant and showed an increase in antibodies to MDA adducts and the carrier
      protein as the concentration of MDA was increased. In fact, a number of the
      commercially available antibodies to MDA-modified proteins were able to be
      inhibited by a chemical analogue, hexyl-MAA. Also, MDA-MAA adducts were detected
      in the serum and aortic tissue of JCR diabetic/atherosclerotic rats. These
      studies determined that commercially available antibodies to MDA predominantly
      react with the MAA adduct and are present in the JCR model of atherosclerosis in
      both the serum and the aortic tissue. Therefore, the immune response to MDA
      modified proteins is most probably to the dihydropyridine structure (predominant
      epitope in MAA), which suggests that MAA adducts may play a role in the
      development and/or progression of atherosclerosis.

PMID- 20696237
TI  - Roles of dioxins and heavy metals in cancer and neurological diseases using ROS
      mediated mechanisms.
AB  - Oxidants have critical functions inside healthy and unhealthy cells. Deregulated
      cell cycle and apoptosis, both regulated by oxidative stress, have been described
      as hallmarks of mitotic (cancer) and postmitotic (neuronal) cells. This review
      provides an updated revision of the oxidant effects of some environmental
      contaminants such as dioxins and the heavy metals cadmium, cobalt, and copper.
      Dioxins exert their toxic actions by acting on phase I and phase II enzymes, such
      as cytochromes P450, superoxide dismutase, and glutathione peroxidase, promoting
      cell proliferation, growth arrest, and apoptosis, affecting cancer homeostasis
      and neuronal function. Heavy metals manifest cytotoxic effects in various cells
      and tissues, and tight regulation of metals is essential to the health of
      organisms. Cadmium modulates gene expression and signal transduction and reduces
      activities of proteins involved in antioxidant defense, interfering with DNA
      repair and modifying cancer development and brain function. Cobalt provokes
      generation of reactive oxygen species and DNA damage in cancer cells and brain
      tissues, altering proliferation and differentiation and causing apoptosis. Copper
      is a key metal in cell division processes in both normal and tumor cells. Copper
      also has been shown to have an important role in neurodegenerative diseases such
      as Alzheimer disease, Parkinson disease, and amyotrophic lateral sclerosis.

PMID- 20696239
TI  - beta-Galactofuranose-containing structures present in the cell wall of the
      saprophytic fungus Cladosporium (Hormoconis) resinae.
AB  - A peptidogalactomannan was isolated from mycelia of Cladosporium (Hormoconis)
      resinae and characterized using methylation-fragmentation analysis, partial acid
      hydrolysis and 1H and 13C-NMR spectroscopy. The galactomannan component was a
      branched structure and consisted of a main chain containing (1->6)-linked alpha-d
      Manp residues substituted at O-2 by side chains containing (1->2)-linked alpha-D
      Manp residues. beta-D-Galf residues were present as side chains of 3-4 units that
      are (1->5)-interlinked. This structure is very similar to a pGM isolated from
      Aspergillus fumigatus and differs from that of Cladosporium werneckii (currently
      named Hortaea werneckii), with this pGM and other fungal galactomannans having
      single terminal (1->6)-linked beta-Galf residues. The importance of the
      carbohydrate moiety of Cladosporium resinae pGM in immunoassays was also
      demonstrated. On FACS examination, a decrease (60%) in rabbit serum anti- C.
      resinae binding to C. resinae conidia occurred when this serum had been
      previously incubated with pGMs from C. resinae and A. fumigatus or with
      mannoprotein from Candida parapsilosis, suggesting the presence of cross-reactive
      determinants in these fungi.

PMID- 20696238
TI  - Nox enzymes from fungus to fly to fish and what they tell us about Nox function
      in mammals.
AB  - The production of reactive oxygen species (ROS) in a highly regulated fashion is
      a hallmark of members of the NADPH oxidase (Nox) family of enzymes. Nox enzymes
      are present in most eukaryotic groups such as the amebozoid, fungi, algae and
      plants, and animals, in which they are involved in seemingly diverse biological
      processes. However, a comprehensive survey of Nox functions throughout biology
      reveals common functional themes. Noxes are often activated in response to
      stressful conditions such as nutrient starvation, physical damage, or pathogen
      attack. Although the end result varies depending on the organism and tissue, Nox
      produced ROS mediate the response to the adverse stimuli, such as innate immunity
      responses in plants and animals or cell differentiation in Dictyostelium, fungi,
      and plants. These responses involve ROS-mediated signaling mechanisms occurring
      at intracellular or cell-to-cell levels and sometimes involve cell wall or
      extracellular matrix cross-linking. Indeed, Noxes are involved in local and
      systemic signaling from plants to fish and in cross-linking of the plant hair
      cell wall, synthesis of the nematode cuticle, and formation of the sea urchin
      fertilization envelope. The extensive use of Nox enzymes in biology to regulate
      cell-to-cell signaling and morphogenesis suggests that additional functions in
      mammalian signaling and development remain to be discovered.

PMID- 20696240
TI  - Human endogenous retroviruses and multiple sclerosis: innocent bystanders or
      disease determinants?
AB  - Human endogenous retroviruses (HERVs) constitute 5-8% of human genomic DNA and
      are replication incompetent despite expression of individual HERV genes from
      different chromosomal loci depending on the specific tissue. Several HERV genes
      have been detected as transcripts and proteins in the central nervous system,
      frequently in the context of neuroinflammation. The HERV-W family has received
      substantial attention in large part because of associations with diverse
      syndromes including multiple sclerosis (MS) and several psychiatric disorders. A
      HERV-W-related retroelement, multiple sclerosis retrovirus (MSRV), has been
      reported in MS patients to be both a biomarker as well as an effector of aberrant
      immune responses. HERV-H and HERV-K have also been implicated in MS and other
      neurological diseases but await delineation of their contributions to disease.
      The HERV-W envelope-encoded glycosylated protein, syncytin-1, is encoded by
      chromosome 7q21 and exhibits increased glial expression within MS lesions.
      Overexpression of syncytin-1 in glia induces endoplasmic reticulum stress leading
      to neuroinflammation and the induction of free radicals, which damage proximate
      cells. Syncytin-1's receptor, ASCT1 is a neutral amino acid transporter expressed
      on glia and is suppressed in white matter of MS patients. Of interest,
      antioxidants ameliorate syncytin-1's neuropathogenic effects raising the
      possibility of using these agents as therapeutics for neuroinflammatory diseases.
      Given the multiple insertion sites of HERV genes as complete and incomplete open
      reading frames, together with their differing capacity to be expressed and the
      complexities of individual HERVs as both disease markers and bioactive effectors,
      HERV biology is a compelling area for understanding neuropathogenic mechanisms
      and developing new therapeutic strategies.

PMID- 20696241
TI  - Functional analysis of F508del CFTR in native human colon.
AB  - The major cystic fibrosis mutation F508del has been classified by experiments in
      animal and cell culture models as a temperature-sensitive mutant defective in
      protein folding, processing and trafficking, but literature data on F508del CFTR
      maturation and function in human tissue are inconsistent. In the present study
      the molecular pathology of F508del CFTR was characterized in freshly excised
      rectal mucosa by bioelectric measurement of the basic defect and CFTR protein
      analysis by metabolic labelling or immunoblot. The majority of investigated
      F508del homozygous subjects expressed low amounts of complex-glycosylated mature
      F508del CFTR and low residual F508del CFTR-mediated chloride secretory activity
      in the rectal mucosa. The finding that some F508del CFTR escapes the ER quality
      control in vivo substantiates the hope that the defective processing and
      trafficking of F508del CFTR can be corrected by pharmacological agents.

PMID- 20696242
TI  - Different altered pattern expression of genes related to apoptosis in isolated
      methylmalonic aciduria cblB type and combined with homocystinuria cblC type.
AB  - An increased reactive oxygen species (ROS) production and apoptosis rate have
      been associated with several disorders involved in cobalamin metabolism,
      including isolated methylmalonic aciduria (MMA) cblB type and MMA combined with
      homocystinuria (MMAHC) cblC type. Given the relevance of p38 and JNK kinases in
      stress-response, their activation in fibroblasts from a spectrum of patients
      (mut, cblA, cblB, cblC and cblE) was analyzed revealing an increased expression
      of the phosphorylated-forms, specially in cblB and cblC cell lines that presented
      the highest ROS and apoptosis levels. To gain further insight into the molecular
      mechanisms responsible for the enhanced apoptotic process observed in cblB and
      cblC fibroblasts, we evaluated the expression pattern of 84 apoptosis-related
      genes by quantitative real-time PCR. An elevated number of pro-apoptotic genes
      were overexpressed in cblC cells showing a higher rate of apoptosis compared to
      cblB and control samples. Additionally, apoptosis appears to be mainly triggered
      through the extrinsic pathway in cblC, while the intrinsic pathway was primarily
      activated in cblB cells. The differences observed regarding the apoptosis rate
      and preferred pathway between cblB and cblC patients, who both built up
      methylmalonic acid, might be explained by the accumulated homocysteine in the
      cblC group. The loss of MMACHC function in cblC patients might be partially
      responsible for the oxidative stress and apoptosis processes observed in these
      cell lines. Our results suggest that ROS production may represent a genetic
      modifier of the phenotype and support the potential of using antioxidants as a
      novel therapeutic strategy to improve the severe neurological outcome of these
      rare diseases.

PMID- 20696243
TI  - The tensile strength of bilayered tablets made from different grades of
      microcrystalline cellulose.
AB  - The aim of this work was to determine the tensile strength of bilayered tablets
      made from different grades of microcrystalline cellulose. While these grades are
      chemically identical, they differ significantly in their particle size
      distribution and in their mechanical properties such as Young's modulus of
      elasticity. Tablets were produced in the shape of beams of similar dimensions
      using uniaxial compression, and solid beams made from one material only were
      compared with bilayered beams made from various combinations of powders. It was
      found that in the production of layered tablets it is important for the purpose
      of quality assurance and control that the upper and lower layer of the compact
      can be identified. Otherwise, tensile strength measurements will result in large
      variability depending on which layer faces upwards during the test. Both particle
      size and Young's modulus of elasticity influenced the overall strength of layered
      tablets. If the material forming the lower layer was more elastic, then the beam
      strength was reduced due to tension introduced into the system, acting especially
      at the layer interface and potentially causing partial or complete delamination.
      Larger differences in the particle size of the materials forming the tablet
      layers resulted in an overall reduced compact tensile strength.

PMID- 20696244
TI  - N-(2-Hydroxypropyl)methacrylamide-based polymer conjugates with pH-controlled
      activation of doxorubicin for cell-specific or passive tumour targeting.
      Synthesis by RAFT polymerisation and physicochemical characterisation.
AB  - Controlled radical reversible addition-fragmentation chain transfer (RAFT)
      polymerisation was used to prepare water-soluble polymer-drug carriers based on
      copolymers of N-(2-hydroxypropyl)methacrylamide (HPMA) with a hydrazide group
      containing monomer, showing well-defined structure with narrow molecular weight
      distribution (approx. 1.1-1.2). The anticancer therapeutic doxorubicin was bound
      to the polymeric carrier by a hydrazone bond, enabling pH-controlled release
      under mildly acid conditions that mimics the environment in endosomes/lysosomes
      of tumour cells. RAFT polymerisation facilitated the synthesis of semitelechelic
      copolymers, which were used in the synthesis of monoclonal anti-CD20 antibody
      polymer-drug conjugate designed for cell-specific tumour targeting. They were
      also used for producing a biodegradable high-molecular-weight graft polymer-drug
      conjugate that degrade in the presence of glutathione, which is designed for
      passive targeting to solid tumours. The conjugates exhibited well-defined
      structures with narrow molecular weight distributions of approx. 1.3 and pH
      controlled drug release.

PMID- 20696245
TI  - Loss of dopaminergic neurons and resulting behavioural deficits in mouse model of
      Angelman syndrome.
AB  - E6 associated protein is an E3 ubiquitin ligase encoded by the gene Ube3a.
      Deletion or loss of function of the maternally inherited allele of Ube3a leads to
      Angelman syndrome. In the present study, we show that maternal loss of Ube3a
      (Ube3a(m-/p+)) in the mouse model leads to motor deficits that could be
      attributed to the dysfunction of the nigrostriatal pathway. The number of
      tyrosine hydroxylase positive neurons in the substantia nigra was significantly
      reduced in Ube3a(m-/p+) mice as compared to the wild type counterparts. The
      Ube3a(m-/p+) mice performed poorly in behavioural paradigms sensitive to
      nigrostriatal dysfunction. Even though the tyrosine hydroxylase staining was
      apparently the same in the striatum of both genotypes, the presynaptic and
      postsynaptic proteins were significantly reduced in Ube3a(m-/p+) mice. These
      findings suggest that the abnormality in the nigrostriatal pathway along with the
      cerebellum produces the observed motor dysfunctions in Ube3a(m-/p+) mice.

PMID- 20696246
TI  - Overexpression of glia maturation factor reinstates susceptibility to myelin
      oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis in
      glia maturation factor deficient mice.
AB  - Glia maturation factor (GMF), a primarily CNS localized protein was discovered
      and characterized in our laboratory. We previously demonstrated that GMF is the
      upstream regulator for excessive production and release of proinflammatory
      cytokines/chemokines in brain cells leading to the destruction of
      oligodendrocytes, the myelin forming cells, and neurons. We also reported that
      mice lacking endogenous GMF (GMF-deficient, GMF-KO) were resistant to myelin
      oligodendrocyte glycoprotein peptide 35-55 (MOG(35-55)) induced EAE, since
      immunization induced only delayed EAE with diminished severity. In the present
      study we show that a replication-defective adenovirus-GMF construct caused
      expression of GMF in CNS of GMF-KO mice and reinstated MOG(35-55) induced early
      and severe EAE. Our results show that MOG(35-55) immunization caused only a muted
      EAE and inflammation/demyelination in mice lacking endogenous GMF. The diminished
      incidence of EAE in GMF-KO mice was consistent with the significantly reduced
      expressions of cytokines/chemokines. The muted severity of EAE in GMF-KO mice was
      restored to full blown levels upon reintroduction of GMF using an adeno-GMF-virus
      (Adv-GMF) vector. Consistent with the clinical findings, histological examination
      of the CNS of mice with EAE revealed profound differences between wild type (Wt),
      GMF-KO, and GMF-KO mice with re-introduced GMF (GMF-KO+Adv-GMF). Spinal cord
      sections from mice with EAE were analyzed for the infiltration of mononuclear
      cells (inflammation) and myelin loss (demyelination). In Wt mice, 40% of spinal
      cord quadrants were positive for demyelination and 45% of spinal cord quadrants
      were positive for inflammation at the peak of EAE. Drastically reduced
      infiltrates (15%) and demyelination (10%) were found in GMF-KO mice that
      developed reduced severity of EAE. Upon GMF reintroduction in GMF-KO mice, MOG(35
      55) immunization caused extensive monocytes infiltration (48%) and demyelination
      (46%), similar to that observed in the immunized Wt mice. The levels of
      cytokine/chemokine in the spinal cords of mice at three time points,
      corresponding to the onset, peak severity and recovery period of EAE, show a
      distinct pattern of very large increases in IFN-gamma, TNF-alpha, GM-CSF and MCP
      1 in Wt and GMF-KO+Adv-GMF mice compared to GMF-KO and GMF-KO+Adv-LacZ mice.

PMID- 20696247
TI  - L1cam acts as a modifier gene during enteric nervous system development.
AB  - The enteric nervous system is derived from neural crest cells that migrate from
      the caudal hindbrain and colonise the gut. Failure of neural crest cells to fully
      colonise the gut results in an "aganglionic zone" that lacks a functional enteric
      nervous system over a variable length of the distal bowel, a condition in human
      infants known as Hirschsprung's disease. The variability observed in the
      penetrance and severity of Hirschsprung's disease suggests a role for modifier
      genes. Clinical studies have identified a population of Hirschsprung's patients
      with mutations in L1CAM that also have a common polymorphism in RET, suggesting a
      possible interaction between L1CAM and RET. Therefore, we examined whether L1cam
      could interact with Ret, its ligand Gdnf, and a known transcriptional activator
      of Ret, Sox10. Using a two-locus complementation approach, we show that loss of
      L1cam in conjunction with a heterozygous loss of Ret or Gdnf did not result in
      aganglionosis. However, L1cam did interact with Sox10 to significantly increase
      the incidence of aganglionosis. We show that an interaction between L1cam and
      Sox10 significantly perturbs neural crest migration within the developing gut,
      and that neural crest cells undergo excessive cell death prior to gut entry.
      Finally, we show that Sox10 can regulate the expression of L1cam. Thus, L1cam can
      act as a modifier gene for the HSCR associated gene, Sox10, and is likely to play
      a role in the etiology of Hirschsprung's disease.

PMID- 20696248
TI  - K63-linked ubiquitination and neurodegeneration.
AB  - The proteasome, which identifies and destroys unwanted proteins rapidly, plays a
      vital role in maintaining cellular protein homeostasis. Proteins that are
      destined for proteasome-mediated degradation are usually tagged with a chain of
      ubiquitin linked via lysine (K) 48 that targets them to the proteolytic
      machinery. However, when the proteasome becomes compromised in its function, it
      is attractive to think that the cell may switch to an alternative, non
      proteolytic form of ubiquitination that could help divert cargo proteins away
      from an otherwise overloaded proteasome. Of the several types of ubiquitin chain
      topologies, K63-linked ubiquitination is the only one known to fulfil diverse
      proteasome-independent roles, including DNA repair, endocytosis and NFkappaB
      signaling. By virtue of its apparent dissociation from the proteasome, we have
      originally proposed that K63-linked ubiquitination may be involved in cargo
      diversion during proteasomal stress and accordingly, in the biogenesis of
      inclusion bodies associated with neurodegenerative diseases. Here, we provide an
      overview of this non-classic form of ubiquitin modification, and discuss current
      evidence and controversies surrounding our proposed role for K63 polyubiquitin as
      a key regulator of inclusion dynamics that is relevant to neurodegeneration. This
      article is part of a Special Issue entitled "Autophagy and protein degradation in
      neurological diseases."

PMID- 20696250
TI  - EHD1 is a synaptic protein that modulates exocytosis through binding to snapin.
AB  - EHD1 is an EH (Eps15 homology) domain-containing protein involved in endosomal
      recycling. Our yeast two hybrid screening experiments showed that EHD1 interacts
      with a synaptic protein, snapin, and the present study was carried out to further
      elucidate the functional significance of this interaction. Immunoreactivity to
      EHD1 is observed in the cerebral cortex, hippocampus and striatum, in the rat
      brain. The protein is colocalized with the axon terminal marker synaptophysin in
      cultured neurons. EHD1 binds to the C terminus of snapin via its C terminus EH
      domain. It negatively affects the binding of a SNARE complex protein, SNAP-25, to
      snapin, probably due to the competition for overlapping binding sites on the C
      terminus of snapin. EHD1 affects the coupling of synaptotagmin-1 to the SNARE
      complex, and could be a negative regulator of exocytosis. This is supported by
      electrophysiological findings that PC-12 cells which overexpress EHD1 show
      reduced depolarization-induced exocytosis compared to controls, but the reduced
      exocytosis is not observed in cells which overexpress the N terminus of EHD1 that
      is unable to bind snapin. Together, the above results indicate that EHD1 is a
      synaptic protein that negatively affects exocytosis through binding to snapin.

PMID- 20696249
TI  - Hypercholesterolemia in rats impairs the cholinergic system and leads to memory
      deficits.
AB  - Alzheimer's disease (AD) is a chronic brain disorder characterized by cognitive
      impairment, cholinergic dysfunction, inflammation, tau and beta-amyloid pathology
      and vascular damage. Recent studies have shown, that high cholesterol levels are
      linked to the pathology of AD. The aim of our present work was to study the
      effects of hypercholesterolemia in adult rats. Five months after 5% cholesterol
      enriched diet plasma cholesterol levels and total weight were significantly
      enhanced compared to controls. Spatial memory was studied in an 8-arm radial maze
      and cholesterol-treated rats showed an impaired learning and long-term memory.
      Hypercholesterolemia significantly reduced the number of cholinergic neurons in
      the basal nucleus of Meynert and decreased acetylcholine levels in the cortex.
      Nerve growth factor was only slightly enhanced in the cortex of cholesterol
      treated animals. Levels of amyloid precursor protein, beta-amyloid(1-42), as well
      as tau and phospho-tau 181 were significantly enhanced in the cortex of
      cholesterol-fed rats. Hypercholesterolemia markedly increased several cerebral
      inflammatory markers and enhanced microglial CD11b-like immunoreactivity.
      Vascular density, stained by RECA-1 was not changed. However, cholesterol induced
      cortical microbleedings illustrated by intensive anti-rat IgG-positive spots in
      the cortex. In conclusion, our data demonstrate that hypercholesterolemia in rats
      caused memory impairment, cholinergic dysfunction, inflammation, enhanced
      cortical beta-amyloid and tau and microbleedings, all indications, which resemble
      an AD-like pathology.

PMID- 20696252
TI  - Nanoscale morphology of Type I collagen is altered in the Brtl mouse model of
      Osteogenesis Imperfecta.
AB  - Bone has a complex hierarchical structure that has evolved to serve structural
      and metabolic roles in the body. Due to the complexity of bone structure and the
      number of diseases which affect the ultrastructural constituents of bone, it is
      important to develop quantitative methods to assess bone nanoscale properties.
      Autosomal dominant Osteogenesis Imperfecta results predominantly from glycine
      substitutions (80%) and splice site mutations (20%) in the genes encoding the
      alpha1 or alpha2 chains of Type I collagen. Genotype-phenotype correlations using
      over 830 collagen mutations have revealed that lethal mutations are located in
      regions crucial for collagen-ligand binding in the matrix. However, few of these
      correlations have been extended to collagen structure in bone. Here, an atomic
      force microscopy-based approach was used to image and quantitatively analyze the
      D-periodic spacing of Type I collagen fibrils in femora from heterozygous
      (Brtl/+) mice (alpha1(I)G349C), compared to wild type (WT) littermates. This
      disease system has a well-defined change in the col1alpha1 allele, leading to a
      well characterized alteration in collagen protein structure, which are directly
      related to altered Type I collagen nanoscale morphology, as measured by the D
      periodic spacing. In Brtl/+ bone, the D-periodic spacing shows significantly
      greater variability on average and along the length of the bone compared to WT,
      although the average spacing was unchanged. Brtl/+ bone also had a significant
      difference in the population distribution of collagen D-period spacings. These
      changes may be due to the mutant collagen structure, or to the heterogeneity of
      collagen monomers in the Brtl/+ matrix. These observations at the nanoscale level
      provide insight into the structural basis for changes present in bone
      composition, geometry and mechanical integrity in Brtl/+ bones. Further studies
      are necessary to link these morphological observations to nanoscale mechanical
      integrity.

PMID- 20696251
TI  - Transcriptional profiling of intrinsic PNS factors in the postnatal mouse.
AB  - Neurons in the peripheral nervous system (PNS) display a higher capacity to
      regenerate after injury than those in the central nervous system, suggesting cell
      specific transcriptional modules underlying axon growth and inhibition. We report
      a systems biology based search for PNS specific transcription factors (TFs).
      Messenger RNAs enriched in dorsal root ganglion (DRG) neurons compared to
      cerebellar granule neurons (CGNs) were identified using subtractive hybridization
      and DNA microarray approaches. Network and transcription factor binding site
      enrichment analyses were used to further identify TFs that may be differentially
      active. Combining these techniques, we identified 32 TFs likely to be enriched
      and/or active in the PNS. Twenty-five of these TFs were then tested for an
      ability to promote CNS neurite outgrowth in an overexpression screen. Real-time
      PCR and immunohistochemical studies confirmed that one representative TF, STAT3,
      is intrinsic to PNS neurons, and that constitutively active STAT3 is sufficient
      to promote CGN neurite outgrowth.

PMID- 20696253
TI  - Identification of genes from flat oyster Ostrea edulis as suitable housekeeping
      genes for quantitative real time PCR.
AB  - Bonamia ostreae is an intrahaemocytic protozoan affecting Ostrea edulis. The
      parasite multiplies within haemocytes without being degraded and involves changes
      in cellular activities. Studies aiming at better understanding host response to a
      pathogen at the transcriptome levels are frequently based on the use of real time
      PCR assays, which require some reference genes. However, very few sequence data
      is available for O. edulis in public databases. Subtracted cDNA libraries were
      constructed from the O. edulis haemocytes in order to identify genes involved in
      host reactions against the parasite and quantitative real time PCR assays were
      developed to study expression of these genes. In this context, identification of
      reference genes and study of their relative expression stability were required
      for quantitative real time PCR normalization. The expression of 5 potential
      candidate reference genes from O. edulis (ie elongation factor 1 alpha (EF1
      alpha), 60S ribosomal protein L5 (L5), glyceraldehyde 3-phosphate-dehydrogenase
      (GAPDH), polyubiquitin (Ubiq) and beta-actin (ACT)) was studied using RNAs
      extracted from pools of haemocytes in contact with the parasite B. ostreae and
      haemocytes alone. Gene expression was quantified by real time PCR and expression
      stability was analysed with two analytical approaches GeNorm and NormFinder.
      GAPDH and EF1-alpha were identified as the most stable genes with the GeNorm
      analysis. Whatever were the tested conditions, EF1-alpha was also found as the
      most stable gene using Normfinder. The less stable gene was beta-actin although
      this gene is commonly used as housekeeping gene in many studies. Our results
      suggest using GAPDH and EF1-alpha combined as reference genes when studying
      expression levels in haemocytes of O. edulis. In addition, the complete ORF of
      these two genes was characterized.

PMID- 20696254
TI  - Simultaneous recording of ECoG and intracortical neuronal activity using a
      flexible multichannel electrode-mesh in visual cortex.
AB  - Electrocorticogram (ECoG) is a well-balanced methodology for stably mapping brain
      surface local field potentials (LFPs) over a wide cortical region with high
      signal fidelity and minimal invasiveness to the brain tissue. To directly compare
      surface ECoG signals with intracortical neuronal activity immediately underneath,
      we fabricated a flexible multichannel electrode array with mesh-form structure
      using micro-electro-mechanical systems. A Parylene-C-based "electrode-mesh" for
      rats contained a 6*6 gold electrode array with 1-mm interval. Specifically, the
      probe had 800*800 MUm(2) fenestrae in interelectrode spaces, through which
      simultaneous penetration of microelectrode was capable. This electrode-mesh was
      placed acutely or chronically on the dural/pial surface of the visual cortex of
      Long-Evans rats for up to 2 weeks. We obtained reliable trial-wise profiles of
      visually evoked ECoG signals through individual eye stimulation. Visually evoked
      ECoG signals from the electrode-mesh exhibited as well or larger signal
      amplitudes as intracortical LFPs and less across-trial variability than
      conventional silver-ball ECoG. Ocular selectivity of ECoG responses was
      correlated with that of intracortical spike/LFP activities. Moreover, single
      trial ECoG signals carried sufficient information for predicting the stimulated
      eye with a correct performance approaching 90%, and the decoding was
      significantly generalized across sessions over 6 hours. Electrode impedance or
      signal quality did not obviously deteriorate for 2 weeks following implantation.
      These findings open up a methodology to directly explore ECoG signals with
      reference to intracortical neuronal sources and would provide a key to developing
      minimally invasive next-generation brain-machine interfaces.

PMID- 20696255
TI  - Does compensatory neural activity survive old-old age?
AB  - One mechanism that may allow older adults to continue to successfully perform
      certain cognitive tasks is to allocate more resources than their younger
      counterparts. Most prior studies have not included individuals beyond their 70s.
      Here, we investigated whether compensatory increases in neural activity
      previously observed in cognitively high-performing young-old adults would
      continue into old-old age. Event-related potentials were recorded from 72
      cognitively high performing subjects, aged 18 to 96 years old, while they
      participated in a subject-controlled novelty oddball paradigm in which they
      determined viewing duration of standard, target, and novel visual stimuli.
      Compared to young and middle-aged subjects, both young-old and old-old subjects
      exhibited an impairment of preliminary mismatch/match detection operations,
      indexed by an attenuated anterior N2 component. This may have placed a greater
      burden on the subsequent controlled decision-making process, indexed by the P3,
      necessitating the allocation of more resources. The relationship between age and
      resource allocation, as measured by P3 amplitude, from midlife to very old age
      (45-96 years old) followed an inverted u-shaped curve (quadratic function). It
      peaked between the late 60s and early 70s. Thereafter, there was an inverse
      relationship between age and resource appropriation. This relationship remained
      significant after controlling for differences in task performance and MMSE.
      Examining the size of the P3 component across different age groups suggests that
      although cognitively high performing adults in their early 80s exhibit a
      reduction in P3 amplitude, they have a relatively well-preserved capacity to
      appropriate resources. However, by the late 80s, there is a robust decline
      (relative to young-old adults) in the size of the P3. Our results indicate that
      when carrying out controlled processing linked to directing attention to salient
      events, cognitively high performers reach the boundary of their capacity, albeit
      relatively late in life. This limits their ability to appropriate additional
      resources as compensatory activity for age-related impairments in earlier visual
      processing, and suggests that such a mechanism does not tend to "survive" old-old
      age.

PMID- 20696256
TI  - Manifestation of ocular-muscle EMG contamination in human intracranial
      recordings.
AB  - It is widely assumed that intracranial recordings from the brain are only
      minimally affected by contamination due to ocular-muscle electromyogram (oEMG).
      Here we show that this is not always the case. In intracranial recordings from
      five surgical epilepsy patients we observed that eye movements caused a transient
      biphasic potential at the onset of a saccade, resembling the saccadic spike
      potential commonly seen in scalp EEG, accompanied by an increase in broadband
      power between 20 and 200 Hz. Using concurrently recorded eye movements and high
      density intracranial EEG (iEEG) we developed a detailed overview of the spatial
      distribution and temporal characteristics of the saccade-related oculomotor
      signal within recordings from ventral, medial and lateral temporal cortex. The
      occurrence of the saccadic spike was not explained solely by reference contact
      location, and was observed near the temporal pole for small (<2 deg) amplitude
      saccades and over a broad area for larger saccades. We further examined the
      influence of saccade-related oEMG contamination on measurements of spectral power
      and interchannel coherence. Contamination manifested in both spectral power and
      coherence measurements, in particular, over the anterior half of the ventral and
      medial temporal lobe. Next, we compared methods for removing the contaminating
      signal and found that nearest-neighbor bipolar re-referencing and ICA filtering
      were effective for suppressing oEMG at locations far from the orbits, but tended
      to leave some residual contamination at the temporal pole. Finally, we show that
      genuine cortical broadband gamma responses observed in averaged data from ventral
      temporal cortex can bear a striking similarity in time course and band-width to
      oEMG contamination recorded at more anterior locations. We conclude that eye
      movement-related contamination should be ruled out when reporting high gamma
      responses in human intracranial recordings, especially those obtained near
      anterior and medial temporal lobe.

PMID- 20696257
TI  - Non-parametric statistical thresholding of baseline free MEG beamformer images.
AB  - Magnetoencephalography (MEG) provides excellent temporal resolution when
      examining cortical activity in humans. Inverse methods such as beamforming (a
      spatial filtering approach) provide the means by which activity at cortical
      locations can be estimated. To date, the majority of work in this field has been
      based upon power changes between active and baseline conditions. Recent work,
      however, has focused upon other properties of the time series data reconstructed
      by these methods. One such metric, the Source Stability Index (SSI), relates to
      the consistency of the time series calculated only over an active period without
      the use of a baseline condition. In this paper we apply non-parametric statistics
      to SSI volumetric maps of simulation, auditory and somatosensory data in order to
      provide a robust and principled method of statistical inference in the absence of
      a baseline condition.

PMID- 20696258
TI  - A comprehensive multilocus phylogeny for the wood-warblers and a revised
      classification of the Parulidae (Aves).
AB  - The birds in the family Parulidae-commonly termed the New World warblers or wood
      warblers-are a classic model radiation for studies of ecological and behavioral
      differentiation. Although the monophyly of a 'core' wood-warbler clade is well
      established, no phylogenetic hypothesis for this group has included a full
      sampling of wood-warbler species diversity. We used parsimony, maximum
      likelihood, and Bayesian methods to reconstruct relationships among all genera
      and nearly all wood-warbler species, based on a matrix of mitochondrial DNA (5840
      nucleotides) and nuclear DNA (6 loci, 4602 nucleotides) characters. The resulting
      phylogenetic hypotheses provide a highly congruent picture of wood-warbler
      relationships, and indicate that the traditional generic classification of these
      birds recognizes many non-monophyletic groups. We recommend a revised taxonomy in
      which each of 14 genera (Seiurus, Helmitheros, Mniotilta, Limnothlypis,
      Protonotaria, Parkesia, Vermivora, Oreothlypis, Geothlypis, Setophaga, Myioborus,
      Cardellina, Basileuterus, Myiothlypis) corresponds to a well-supported clade;
      these nomenclatural changes also involve subsuming a number of well-known,
      traditional wood-warbler genera (Catharopeza, Dendroica, Ergaticus, Euthlypis,
      Leucopeza, Oporornis, Parula, Phaeothlypis, Wilsonia). We provide a summary
      phylogenetic hypothesis that will be broadly applicable to investigations of the
      historical biogeography, processes of diversification, and evolution of trait
      variation in this well studied avian group.

PMID- 20696259
TI  - Unraveling ancient segmental duplication events in human genome by phylogenetic
      analysis of multigene families residing on HOX-cluster paralogons.
AB  - BACKGROUND: Vertebrate genomes contain extensive intra-genomic conserved synteny,
      which is the presence of similar set of genes on two or more chromosomes
      (paralogons). The existence of these paralogons has led to the proposal that
      vertebrate genome was structured by one or more rounds of ancient whole genome
      duplications (2R hypothesis). RESULTS: The 2R hypothesis was tested by
      phylogenetic analysis of gene families residing on human HOX-bearing chromosomes
      (HOX-cluster paralogons). These results revealed that, based on their duplication
      history, 23 gene families with representation on three or four of the human HOX
      bearing chromosomes can be partitioned into four discrete co-duplicated groups.
      The distinct genes within each co-duplicated group share the same evolutionary
      history and are duplicated in concert with each other, while the constituent
      genes of two different co-duplicated groups do not share their evolutionary
      history and are not duplicated simultaneously. These co-duplicated groups are
      large constituting members from 3 to 8 gene families and suggest that human HOX
      cluster paralogons were shaped by ancient segmental duplications (SDs) and
      rearrangement events that occurred at least as early as before the divergence of
      bony fishes and tetrapods. CONCLUSIONS: Based on the recovery of ancient SD
      events in this analysis and given the widespread evidence in favor of the fact
      that recent SD events played a pivotal role in changing genome architecture of
      primates and other recently diverged animals, it is concluded that a more
      realistic model of ancient vertebrate genome evolutionary history can be deduced
      by tracing the evolutionary trajectory of the genomes of recently diverged
      vertebrate species.

PMID- 20696260
TI  - Molecular phylogeny of the genus Luzula DC. (Juncaceae, Monocotyledones) based on
      plastome and nuclear ribosomal regions: a case of incongruence, incomplete
      lineage sorting and hybridisation.
AB  - The genus Luzula consists of 115 species distributed throughout the world. Luzula
      is monophyletic, but species relationships within the genus are difficult to
      determine primarily due to the similar morphology even within geographically
      remote taxa (especially within the section Luzula). The plastome trnL intron,
      trnL-F intergenic spacer and the nuclear ribosomal ITS1-5.8S-ITS2 regions were
      analysed using maximum parsimony and maximum likelihood reconstruction in 93
      species of Luzula. The incongruent phylogenetic signals obtained from the
      chloroplast and the nuclear genomes point to incomplete lineage sorting as well
      as recent hybridisation in this group. Although tree-building analyses revealed
      several well-supported lineages, the outcomes for many groups were ambiguous. In
      the total evidence tree, Luzula species were grouped within six main clades (1.
      subgenus Marlenia, 2. subgenus Pterodes except for L. pilosa, 3. sections
      Anthelaea and Nodulosae, 4. sections Diprophyllatae and Thyrsanochlamydeae, 5.
      section Alpinae except for a few species and 6. section Luzula). The subgenus
      Marlenia occupies the early derived lineage within the genus Luzula. The
      traditionally accepted subgenera Pterodes and Luzula (and its sections) appear to
      be non-monophyletic. A statistical parsimony network approach showed that ancient
      haplotypes and ribotypes co-occur with their descendants in Luzula. Furthermore,
      many haplotypes are shared among different species. Within the Luzula section
      Luzula, both recent hybridisation and incomplete lineage sorting of ancestral
      polymorphisms may represent potential sources of the incongruence between
      chloroplast and nuclear data.

PMID- 20696261
TI  - The evolutionary history and biogeography of Mimosoideae (Leguminosae): an
      emphasis on African acacias.
AB  - The systematics of Mimosoideae has been in a state of flux, which reflects
      overall poor knowledge of the evolution and biogeography of this group.
      Preliminary molecular phylogenetic analyses suggest the tribal system of
      Mimosoideae needs a complete revision. This has led to the use of new generic
      names for Acacia sensu lato (s.l. hereafter) following the re-typification of
      Acacia with an Australian type: (i) Acacia sensu stricto (s.s. hereafter),
      Vachellia, Senegalia, Acaciella and Mariosousa. This study reconstructs the
      evolutionary history of Mimosoideae, using the most comprehensive sampling to
      date, with an emphasis on African species. It aims to reconstruct the
      phylogenetic relationships among the five recognized genera within Acacieae as
      the precursor to elucidate the paleo-biogeography of mimosoids and their
      adaptation to open habitats in the Cenozoic. The basal position of Mimoseae
      lineages with regards to Vachellia and
      Senegalia+Mariosousa+Acaciella+Ingeae+Acacia s.s. clades is a novel finding.
      Vachellia (formerly Acacia subgenus Acacia) is found monophyletic. A grade
      including the remaining Mimoseae lineages is found sister to the
      Senegalia+Mariosousa+Acaciella+Ingeae+Acacia s.s. clade. The major clades
      originated in the late Oligocene-early Miocene (~25mya). The transitions from
      close to open habitats occurred during the Miocene for at least four mimosoid
      lineages. These are interpreted as responses to increased seasonality leading to
      fire climates and drying trends in the Miocene, which allowed the expansion of
      open habitats, such as savannas, worldwide.

PMID- 20696262
TI  - Cartilage and meniscus assessment using T1rho and T2 measurements in healthy
      subjects and patients with osteoarthritis.
AB  - OBJECTIVE: The purpose of this study was to evaluate meniscal degeneration in
      healthy subjects and subjects with osteoarthritis (OA) using T(1rho) and T(2)
      measurements and to examine the interrelationship between cartilage and meniscus
      abnormalities. METHODS: Quantitative assessment of cartilage and meniscus was
      performed using 3T Magnetic Resonance Imaging (MRI) with a T(1rho) and T(2)
      mapping technique in 19 controls and 44 OA patients. A sagittal T(2)-weighted
      fast spin echo (FSE) fat-saturated image was acquired for cartilage and meniscal
      Whole-Organ Magnetic Resonance Imaging Score (WORMS) assessment. Western Ontario
      and McMasters Universities Arthritis Index (WOMAC) scores were obtained to assess
      clinical symptoms. RESULTS: The posterior horn of the medial meniscus (PHMED) had
      the highest incidence of degeneration. Stratifying subjects on the basis of PHMED
      grade revealed that the T(1rho) and the T(2) measurements of the PHMED and the
      medial tibial (MT) cartilage were higher in subjects having a meniscal tear
      (meniscal grade 2-4) compared to subjects with a meniscal grade of 0 or 1
      (P<0.05). While not statistically significant, there was a trend for T(1rho) and
      T(2) being higher in PHMED grade 1 compared to grade 0 (P=0.094, P=0.073
      respectively). WOMAC scores had a stronger correlation with meniscus relaxation
      measures than cartilage measures. CONCLUSIONS: Magnetic Resonance (MR) T(1rho)
      and T(2) measurements provide a non-invasive means of detecting and quantifying
      the severity of meniscal degeneration. Meniscal damage has been implicated in OA
      progression and is correlated with cartilage degeneration. Early detection of
      meniscal damage represented by elevations in meniscal relaxation measures may
      identify subjects at increased risk for OA.

PMID- 20696263
TI  - Therapy of sclerodermatous chronic graft-versus-host disease with mammalian
      target of rapamycin inhibitors.
AB  - This retrospective study analyzes 34 patients with severe sclerodermatous chronic
      graft-versus-host disease (cGVHD) treated with inhibitors of the mammalian target
      of rapamycin (mTOR-I). Twelve patients received mTOR-I as monotherapy and 22 a
      combination therapy. Four patients also received extracorporal photopheresis.
      mTOR-I were applied as first-line therapy (n = 15) or in refractory disease (n =
      19). Drug doses were adjusted to low therapeutical levels (3-8 ng/mL). Six and 20
      patients had a complete and a partial response, respectively, with an overall
      response rate of 76%. Two additional patients had stable disease. Six refractory
      patients required alternative therapy. Comedication, especially steroids, could
      be tapered and stopped in a significant number of patients. No difference in
      response was observed in everolimus- and sirolimus-treated patients. Major
      adverse events possibly related to mTOR-I were hyperlipidemia and impaired wound
      healing. Two patients developed thrombotic microangiopathy. Eight patients died,
      5 of the nonresponders (cGVHD; n = 3, infection; n = 2) and 3 of the responders
      (relapse of the underlying malignancy; n = 1, secondary malignancy; n = 1,
      unknown cause; n = 1). Twenty-six of the 34 patients remain alive, 18 still on
      therapy with mTOR-I. Median follow-up for surviving patients is 723 days (range
      88-1621). The overall survival at 3 years since mTOR-I is 72%. In conclusion,
      mTOR-I seem to be an effective and well-tolerated treatment option for patients
      with sclerodermatous cGVHD.

PMID- 20696264
TI  - Myostatin from the American lobster, Homarus americanus: Cloning and effects of
      molting on expression in skeletal muscles.
AB  - A cDNA encoding a myostatin (Mstn)-like gene from an astacuran crustacean,
      Homarus americanus, was cloned and characterized. Mstn inhibits skeletal muscle
      growth in vertebrates and may play a role in crustacean muscle as a suppressor of
      protein synthesis. Sequence analysis and three-dimensional modeling of the Ha
      Mstn protein predicted a high degree of conservation with vertebrate and other
      invertebrate myostatins. Qualitative polymerase chain reaction (PCR) demonstrated
      ubiquitous expression of transcript in all tissues, including skeletal muscles.
      Quantitative PCR analysis was used to determine the effects of natural molting
      and eyestalk ablation (ESA) on Ha-Mstn expression in the cutter claw (CT) and
      crusher claw (CR) closer muscles and deep abdominal (DA) muscle. In intermolt
      lobsters, the Ha-Mstn mRNA level in the DA muscle was significantly lower than
      the mRNA levels in the CT and CR muscles. Spontaneous molting decreased Ha-Mstn
      mRNA during premolt, with the CR muscle, which is composed of slow-twitch (S1)
      fibers, responding preferentially (82% decrease) to the atrophic signal compared
      to fast fibers in CT (51% decrease) and DA (69% decrease) muscles. However, acute
      increases in circulating ecdysteroids caused by ESA had no effect on Ha-Mstn mRNA
      levels in the three muscles. These data indicate that the transcription of Ha
      Mstn is differentially regulated during the natural molt cycle and it is an
      important regulator of protein turnover in molt-induced claw muscle atrophy.

PMID- 20696265
TI  - Ammonia uptake in Manduca sexta midgut is mediated by an amiloride sensitive
      cation/proton exchanger: Transport studies and mRNA expression analysis of NHE7,
      9, NHE8, and V-ATPase (subunit D).
AB  - In this study participation of cation/proton exchangers (NHE) in ammonia uptake
      in the medial midgut of Manduca sexta larvae was investigated employing a
      modified Ussing chamber. There was a mean inward net ammonia (NH3 + NH4+) flux of
      194 +/- 17 nmol cm-2 h-1 across the isolated epithelium under conditions of 0.1
      mmol L-1 ammonia on both sides of the tissue and a 100-fold inwardly directed
      P(NH3)-gradient (pH 8.5 luminal side, pH 6.5 hemolymphal side). Employing a 100
      fold NH4+ gradient amiloride applied to the luminal side inhibited the influx in
      a dose-dependent manner, with a maximal inhibition of 75% at 20 mmol L-1 and an
      estimated IC50 = 2 mmol L-1. Amiloride also caused a dose-dependent but smaller
      decrease in the short-circuit current (I(sc)). No inhibition by apical or basal
      applied amiloride was noticed on cellular metabolic ammonia release, of which ca.
      1/3 and 2/3 was secreted towards the apical and basal side, respectively. Using
      molecular methods full and partial sequence information of two putative
      cation/proton exchangers (MsNHE8, MsNHE7, 9) were obtained, both containing the
      characteristic amiloride binding motif. An mRNA expression analysis revealed
      ubiquitous expression patterns for both proteins, with similar expression levels
      for NHE8 in all tissues investigated and lower mRNA abundances for MsNHE7, 9 in
      the midgut sections of the caterpillar. In contrast, in this tissue high
      expression levels of the V-ATPase (D subunit) were detected, likely the sole pump
      responsible for energizing goblet cell K+ excretion, but also involved in
      columnar cell ammonia uptake.

PMID- 20696266
TI  - A hyperpolarization-activated inward current alters swim frequency of the
      pteropod mollusk Clione limacina.
AB  - The pteropod mollusk, Clione limacina, exhibits behaviorally relevant swim speed
      changes that occur within the context of the animal's ecology. Modulation of C.
      limacina swimming speed involves changes that occur at the network and cellular
      levels. Intracellular recordings from interneurons of the swim central pattern
      generator show the presence of a sag potential that is indicative of the
      hyperpolarization-activated inward current (I(h)). Here we provide evidence that
      I(h) in primary swim interneurons plays a role in C. limacina swimming speed
      control and may be a modulatory target. Recordings from central pattern generator
      swim interneurons show that hyperpolarizing current injection produces a sag
      potential that lasts for the duration of the hyperpolarization, a characteristic
      of cells possessing I(h). Following the hyperpolarizing current injection, swim
      interneurons also exhibit postinhibitory rebound (PIR). Serotonin enhances the
      sag potential of C. limacina swim interneurons while the I(h) blocker, ZD7288,
      reduces the sag potential. Furthermore, a negative correlation was found between
      the amplitude of the sag potential and latency to PIR. Because latency to PIR was
      previously shown to influence swimming speed, we hypothesize that I(h) has an
      effect on swimming speed. The I(h) blocker, ZD7288, suppresses swimming in C.
      limacina and inhibits serotonin-induced acceleration, evidence that supports our
      hypothesis.

PMID- 20696267
TI  - Role of insulin and IGF-I on the regulation of glucose metabolism in European sea
      bass (Dicentrarchus labrax) fed with different dietary carbohydrate levels.
AB  - The roles of insulin and insulin-like growth factor-I (IGF-I) in the regulation
      of glucose metabolism were assessed in European sea bass juveniles fed with
      distinct dietary carbohydrate levels. Three isonitrogenous diets were formulated
      to contain 10% (10%PGS) or 30% (30%PGS) pregelatinized starch or no starch
      (control). The highest plasma glucose and insulin levels were observed 6h after
      feeding in fish receiving the 30%PGS diet. Although plasma IGF-I was higher at 6h
      than at 24h after feeding, no effect of dietary carbohydrate level was noticed
      within each sampling time. Increasing dietary carbohydrate level resulted in an
      increase of liver but not of muscle glycogen content. Hepatic glucokinase (GK)
      and glucose-6-phosphate dehydrogenase (G6PD) activities increased with the
      dietary carbohydrate content, whereas pyruvate kinase (PK) activity was higher in
      fish fed the carbohydrate containing diets than the carbohydrate-free diet. GK
      activity was higher 6h than 24h after feeding, whereas the opposite was observed
      for G6PD activity. Data suggest that under the nutritional conditions assayed
      plasma glucose is an insulin secretagogue. Furthermore, insulin appears to have a
      more important role than IGF-I in stimulating hepatic glucose uptake, thus
      enhancing GK activity and leading to an increase in liver glycogen content to
      maintain glucose homeostasis.

PMID- 20696269
TI  - Infectivity of Giardia duodenalis Assemblages A and E for the gerbil and
      axenisation of duodenal trophozoites.
AB  - Establishing in vitro cultures of Giardia duodenalis trophozoites from faecal
      cysts remains very difficult due to poor excystation and bacterial contamination.
      This study investigated an alternative approach starting from duodenal
      trophozoites of gerbils that were artificially infected with field isolates from
      humans (Assemblages A and B) and cattle (Assemblage E and mixed E/A). Gerbil
      infection was successful for Assemblages A (1/1) and B (1/3) from humans, and for
      E (1/2) and mixed E/A (6/6) from cattle. Despite the fact that some isolates
      subsequently failed or were difficult to establish in vitro, several Assemblage A
      and Assemblage E in vitro trophozoite cultures were successful, however,
      subsequent cloning required adaptation of the standard TYI-S-33 medium whereby
      different medium supplements were required for promoting growth. Excess of l
      cysteine (2mg/ml) and ascorbic acid (0.2mg/ml) supported cloning of Assemblage A,
      while l-glutathione (7.8 mg/ml) was required for Assemblage E. This is a first
      description of in vitro axenisation of Assemblage E trophozoites from cattle.

PMID- 20696268
TI  - DNA polymerase structure-based insight on the mutagenic properties of 8
      oxoguanine.
AB  - An aerobic environment burdens DNA polymerase substrates with oxidized substrates
      (DNA and nucleotide pools). A major promutagenic lesion resulting from oxidative
      stress is 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxoG). Guanine oxidation alters
      the hydrogen bonding properties of the base and glycosidic-preference of the
      nucleotide. The favored glycosidic syn-conformation exposes the Hoogsteen edge of
      the base for hydrogen bonding with adenine during DNA synthesis. The cell has
      recognized the threat of this lesion and has evolved an intricate surveillance
      system to provide DNA polymerases with unmodified substrates. Failure to do so
      leads to transversion mutations. Since the mutagenic properties of the base are
      dictated by the anti-syn-conformation of the nucleotide, the molecular
      interactions of 8-oxoG in the confines of the DNA polymerase active site are
      expected to influence its coding potential. Recent structural characterization of
      DNA polymerases from several families with this lesion in the nascent base pair
      binding pocket has provided insight to the mutagenic properties of this modified
      nucleotide. These structures reveal that flexibility around the template-binding
      pocket can permit 8-oxoG to assume an anti- or syn-conformation and code for
      cytosine or adenine incorporation, respectively. In contrast, the binding pocket
      for the incoming nucleotide does not have this flexibility so that 8-oxodGTP
      insertion opposite cytosine is strongly discouraged.

PMID- 20696270
TI  - Structural origin of the green iridescence on the chelicerae of the red-backed
      jumping spider, Phidippus johnsoni (Salticidae: Araneae).
AB  - The structurally coloured chelicerae of jumping spiders (Salticidae) display some
      of the most striking of all colours in this family, in which they predominantly
      occur. Remarkably, however, the source of this iridescence has not been studied.
      For this reason, we chose to investigate the green iridescent chelicerae of the
      red-backed jumping spider, Phidippus johnsoni. The colour is restricted to the
      dorsal region of the basal chelicera segment--the paturon. This was confirmed by
      reflectance measurements taken at normal incidence and in backscatter, which gave
      a peak reflectance in the green (520 nm), arising from the first harmonic of a
      Bragg resonance in the near infrared. Transmission electron microscope analysis
      of the paturon cuticle revealed a stack of 86 layers of alternating low and high
      density materials, identified as air and chitin respectively. Simulations based
      on a periodic multilayer model of the ten outermost layers of this structure gave
      theoretical reflectance spectra, closely matching those observed, suggesting that
      the stack functions as a multilayer reflector for green. The colour is thought to
      function as a conspecific signal, since studies of vision in a closely related
      species, also displaying green chelicerae, have shown that the eyes have a peak
      spectral sensitivity, matching that of the chelicerae.

PMID- 20696271
TI  - The morphological and molecular processes of onychophoran brain development show
      unique features that are neither comparable to insects nor to chelicerates.
AB  - The phylogenetic position of onychophorans is still being debated; however, most
      phylogenies suggest that onychophorans are a sister group to the arthropods. Here
      we have analysed neurogenesis in the brain of the onychophoran Euperipatoides
      kanangrensis. We show that the development of the onychophoran brain is
      considerably different from arthropods. Neural precursors seem to be generated at
      random positions rather than in distinct spatio-temporal domains as has been
      shown in insects and chelicerates. The different mode of neural precursor
      formation is reflected in the homogenous expression of the proneural and
      neurogenic genes. Furthermore, the morphogenetic events that generate the three
      dimensional structure of the onychophoran brain are significantly different from
      arthropods. Despite the different mode of neural precursor formation in insects
      and chelicerates (neuroblasts versus neural precursor groups), brain neurogenesis
      shares more similarities in these arthropods as compared to the onychophoran. Our
      data show that the developmental processes that generate the brain have
      considerably diverged in onychophorans and arthropods.

PMID- 20696272
TI  - Patterning mechanisms and morphological diversity of spider appendages and their
      importance for spider evolution.
AB  - The prosoma of spiders bears different gnathal (labrum, chelicerae, pedipalps)
      and locomotory appendages (legs). In most species these appendages are also used
      for additional functions, e.g. sensing, mating, and courtship. The opisthosoma is
      equipped with four pairs of highly specialized appendages. Two pairs of
      spinnerets are used for silk production and manipulation. The other two pairs of
      appendages are internalized during development and give rise to a complex
      respiratory system of book lungs and tracheae. Thus spiders have a number of
      different appendage types with radically different adult morphologies.
      Furthermore, all these appendage types display significant additional species
      specific diversity correlating with a large spectrum of functions of the
      appendages. Despite this importance of appendage diversity for the evolution of
      the spiders we know relatively little about the genetic patterning mechanisms
      producing this diversity of morphology. We review recent advances concerning the
      developmental genetics of spider appendage diversification, mainly concentrating
      on open questions and future directions of research. We conclude that the deeper
      understanding of appendage development and diversity in spiders can contribute
      significantly not only to evolutionary developmental biology, but also to
      behavioral biology, speciation research and population genetics, and the study of
      sexually dimorphic traits.

PMID- 20696273
TI  - Effect of cadmium exposure on expression of antioxidant gene transcripts in the
      river pufferfish, Takifugu obscurus (Tetraodontiformes).
AB  - Cadmium (Cd) is a non-essential toxic heavy metal with the potential to induce
      oxidative stress. Cd toxicity and its capacity for accumulation in aquatic
      habitats have earned its recognition as a pollutant of immediate and widespread
      concern. To obtain a better understanding of oxidative stress-associated gene
      expression in different tissues, six antioxidant genes such as catalase (CAT),
      glutathione reductase (GR), glutathione peroxidase 1a (GPx1a), glutathione
      peroxidase 1b (GPx1b), Cu/Zn superoxide dismutase (Cu/Zn-SOD), and Mn superoxide
      dismutase (Mn-SOD) were cloned and fully sequenced in the river pufferfish,
      Takifugu obscurus. On tissue specific mRNA expression, the liver showed the
      highest expression when compared to other tissues, even though each antioxidant
      gene showed different modes of expression patterns in the examined tissues. Of
      the various antioxidant genes, GR was the most highly expressed in the liver,
      followed by CAT, GPx1, and Cu/Zn-SOD. For the time-course experiment, all the
      antioxidant genes were significantly induced over time except for Cu/Zn-SOD in
      the liver, and there was a 5-fold induction in hepatic GR, CAT, and Mn-SOD mRNA
      compared to the control. These findings indicate that the liver of T. obscurus
      has a robust antioxidant system. In addition, these results suggest that Cd
      exposure modulates the expression of antioxidant genes, and would indicate that
      the antioxidant genes would be a relevant biomarker of trace metal pollution such
      as Cd exposure in T. obscurus.

PMID- 20696274
TI  - Purification and characterization of tributyltin-binding protein of tiger puffer,
      Takifugu rubripes.
AB  - We successfully purified Trub.TBT-bpalpha, a tributyltin (TBT) binding protein
      (bp) of the tiger puffer, Takifugu rubripes. Tiger puffer was injected
      intraperitoneally with TBT (1.0mg/kg body weight) and Trub.TBT-bpalpha was
      purified from serum by ammonium sulfate fractionation, gel filtration
      chromatography and polyacrylamide gel electrophoresis. Gel electrophoresis
      revealed that the Trub.TBT-bpalpha has a molecular mass of approximately 48.5kDa
      and contains at least 40% N-glycan. The deduced 212 amino acid sequence of the
      protein showed the highest identity (41%, 212 amino acid overlap and E-value: 9e
      42) with TBT-binding protein type 1 (TBT-bp1) of Paralichthys olivaceus (Japanese
      flounder). Analysis of the gene structure of Trub.TBT-bpalpha suggests that this
      protein belongs to the lipocalin superfamily, which may be important in the
      accumulation and elimination of TBT. Phylogenetic analysis suggests that
      functionalization of TBT-bps has occurred during evolution, and that the
      functions of this group of proteins might be important for fish survival.

PMID- 20696275
TI  - A web-based intervention to support increased physical activity among at-risk
      adults.
AB  - Physical inactivity is an important contributor to the development of numerous
      chronic conditions and alone is an independent risk factor for diabetes,
      cardiovascular disease, and depression and yet, most Americans consistently fail
      to achieve the recommended amount of physical activity. As part of Project
      HealthDesign, we designed and prototyped a personal health record application
      (PHA) that delivers and supports a highly individualized, behaviorally based
      lifestyle physical activity intervention for sedentary adults. Through a user
      centered design approach, we engaged consumers, health care providers, and
      personal trainers for multiple facilitated group discussions and structured
      interviews to determine their needs and wants related to an activity PHA. The PHA
      was developed to include elements of evidence-based approaches which help
      participants adopt cognitive and behavioral skills such as goal-setting, self
      monitoring, accepting social support, cognitive restructuring, contingency
      management, decisional balance, and relapse prevention. This PHA demonstrated the
      potential for research-based behavioral interventions to be delivered via a web
      portal. This finding is important for both consumers and their providers who have
      the desire to implement physical activity recommendations, but lack the tools to
      facilitate or undertake such interventions.

PMID- 20696276
TI  - A method to implement fine-grained access control for personal health records
      through standard relational database queries.
AB  - Online personal health records (PHRs) enable patients to access, manage, and
      share certain of their own health information electronically. This capability
      creates the need for precise access-controls mechanisms that restrict the sharing
      of data to that intended by the patient. The authors describe the design and
      implementation of an access-control mechanism for PHR repositories that is
      modeled on the eXtensible Access Control Markup Language (XACML) standard, but
      intended to reduce the cognitive and computational complexity of XACML. The
      authors implemented the mechanism entirely in a relational database system using
      ANSI-standard SQL statements. Based on a set of access-control rules encoded as
      relational table rows, the mechanism determines via a single SQL query whether a
      user who accesses patient data from a specific application is authorized to
      perform a requested operation on a specified data object. Testing of this query
      on a moderately large database has demonstrated execution times consistently
      below 100ms. The authors include the details of the implementation, including
      algorithms, examples, and a test database as Supplementary materials.

PMID- 20696277
TI  - Measuring clinical pathway adherence.
AB  - As clinical pathway adoption continues worldwide, it is necessary to establish
      adherence measurement methods in order to understand the difficulties and results
      of implementation. Adherence measurement literature mostly provides binary
      measurements of adherence to guidelines regarding individual medical activities
      over patient groups. The resulting measurements are of limited value in view of
      the pathways actually followed by individual patients. We develop and test
      dynamic programming formulations for adherence measurement in clinical pathways-
      based on partially ordered data in medical records and pathway definitions. With
      these new methods at hand, we analyze clinical pathway adherence at the
      Cardiovascular Center of Maastricht University Medical Center.

PMID- 20696279
TI  - Mitochondria in response to nutrients and nutrient-sensitive pathways.
AB  - Mitochondria are abundant cellular organelles, and are required for the
      generation of energy through oxidative catabolism. Equally important,
      mitochondria also provide substrates for de novo synthesis of fatty acids and
      multiple amino acids. Mitochondrial functions must therefore be tightly linked to
      cellular nutrient availability. This review focuses on the current knowledge of
      how nutrients affect mitochondria. In particular, we describe how the
      transcriptional profile of the nucleus is altered to mediate this control, and
      the transcription factors that are involved. In addition, we summarize recent
      progress in our understanding of how transcription-independent mechanisms, most
      notably through the cellular energy sensor mTOR, are used to adapt mitochondrial
      functions in respect to cellular metabolic needs.

PMID- 20696280
TI  - Improvement of mitochondrial energy and oxidative balance during intestinal
      differentiation.
AB  - Mitochondria vary in their number and function, but how these variations are
      associated with intestinal cell differentiation remains elusive. The object of
      this study was to investigate the underlying mechanisms of inosine-mediated
      intestinal cell maturation, analysing the effects of this nutrient on metabolic
      functionality, mitochondrial biogenesis and mitochondrial function in human
      colonic cells. The role of oxidative stress in the control of intestinal cell
      growth was also explored. We report the novel finding that inosine-mediated
      differentiation improves aerobic metabolism through an increase in mitochondrial
      bioenergetics and biogenesis in colonic cells, which probably confers them
      greater resistance to cytotoxic oxidative stress.

PMID- 20696281
TI  - Lysosomal-mitochondrial cross-talk during cell death.
AB  - Lysosomes are membrane-bound organelles, which contain an arsenal of different
      hydrolases, enabling them to act as the terminal degradative compartment of the
      endocytotic, phagocytic and autophagic pathways. During the last decade, it was
      convincingly shown that destabilization of lysosomal membrane and release of
      lysosomal content into the cytosol can initiate the lysosomal apoptotic pathway,
      which is dependent on mitochondria destabilization. The cleavage of BID to t-BID
      and degradation of anti-apoptotic BCL-2 proteins by lysosomal cysteine cathepsins
      were identified as links to the mitochondrial cytochrome c release, which
      eventually leads to caspase activation. There have also been reports about the
      involvement of lysosome destabilization and lysosomal proteases in the extrinsic
      apoptotic pathway, although the molecular mechanism is still under debate. In the
      present article, we discuss the cross-talk between lysosomes and mitochondria
      during apoptosis and its consequences for the fate of the cell.

PMID- 20696282
TI  - Catastrophic antiphospholipid syndrome: updated diagnostic algorithms.
AB  - The catastrophic antiphospholipid syndrome (APS) is the most severe form of APS
      with acute multiple organ involvement and small vessel thrombosis. During the
      13th International Congress on Antiphospholipid Antibodies (aPL) a "Catastrophic
      APS Task Force" was developed to discuss the challenges in the diagnosis and
      management of catastrophic APS. The purpose of this paper is to summarize the
      diagnostic challenges (false-positive/negative aPL results and overlap with other
      thrombotic microangiopathies) and propose updated diagnostic algorithms for
      catastrophic APS. Important steps of the diagnostic algorithms include: a)
      history of APS or persistent aPL-positivity; b) three or more organ new
      thrombosis developing in less than a week; c) biopsy diagnosis of
      microthrombosis; and d) other explanations for multiple organ thromboses and/or
      microthrombosis.

PMID- 20696283
TI  - Pregnancy in autoimmune rheumatic diseases: the importance of counselling for old
      and new challenges.
AB  - Rheumatic diseases can affect women during their childbearing age. Therefore,
      physicians should introduce a discussion with the patients about pregnancy and
      its problems. Lupus pregnancies can be successful, even in patients with renal
      disease, when planned in remission state; the use of low dose aspirin was shown
      to be an independent predictor of good outcome, so it can be suggested as a
      preventive measure. Pregnancies in women with Antiphospholipid Syndrome can fail
      even if properly treated, especially when associated with a systemic autoimmune
      disease, a history of both thrombosis and pregnancy morbidity, and a triple
      positivity of antiphospholipid antibody assays. Women with systemic sclerosis
      have generally a good obstetric outcome, except for an increase rate of preterm
      deliveries. Severe disease complications were sometimes reported, but their
      relationship with gestation is not clear yet. Although data on human pregnancy
      are still preliminary, anti-TNF agents are classified as non teratogens in
      contrast to methotrexate and leflunomide. So women affected by aggressive chronic
      arthritis may be treated with anti-TNF in the pre-conceptional period,
      discontinuing the drug as soon as pregnancy starts. In order to increase maternal
      compliance and cope with difficult cases, a multidisciplinary team
      (rheumatologists/internists, obstetricians and neonatologists) should take care
      of patients during pregnancy.

PMID- 20696284
TI  - Autoantibodies to parietal cells as predictors of atrophic body gastritis: a five
      year prospective study in patients with autoimmune thyroid diseases.
AB  - Autoimmune thyroid diseases (AITD) can be associated with autoimmune gastritis
      (AIG), but the frequency of this association is poorly characterized. We
      performed a prospective study to: a) characterize the frequency of parietal cell
      (PCA) and intrinsic factor (IFA) autoantibodies in AITD patients; b) evaluate the
      development of histologically- and functionally-proven AIG after five years and
      to assess the predictive role of PCA for AIG at baseline; and c) analyze the
      trend of PCA levels in the course of the disease. We studied 208 consecutive
      adult patients affected by AITD (166 Hashimoto's thyroiditis, 42 Graves'
      disease). PCA, IFA and plasma gastrin levels were measured with ELISA methods at
      baseline and after 5years. At baseline, 51/208 (24.5%) AITD patients were
      positive for PCA and 10/208 (4.8%) for IFA. 25 out of 54 PCA/IFA-positive AITD
      patients (all without gastric or haematologic symptoms) agreed to participate in
      the follow-up study. After 5years, 6 (24%) of these 25 patients showed a
      histologically proven AIG, with lymphocytic infiltration and/or atrophy of body
      gastric mucosa. The trend analysis of PCA concentration showed that autoantibody
      levels rise progressively over time, reach a peak level and then fall, according
      to the progressive destruction of gastric mucosa and to the disappearance of the
      target autoantigen (proton pump). The presence of PCA predicts the development of
      autoimmune gastritis in AITD patients. Antibody levels measured with a sensitive
      quantitative immunometric method are useful for early diagnosis and early
      treatment of the disease.

PMID- 20696285
TI  - No role for neutrophil elastase in influenza-induced cellular recruitment,
      cytokine production or airway hyperresponsiveness in mice.
AB  - Previous studies have suggested that in vitro modulation of neutrophil chemokines
      and inflammatory cytokines by neutrophil elastase (NE) does not translate to the
      in vivo setting. We aimed to test the role of NE in the recruitment of
      neutrophils, cytokine production and lung function responses to respiratory viral
      infection. To address this, we inoculated neutrophil elastase (NE(-/-)) deficient
      and wild-type (WT) 129Sv mice with 50MUL of 10(4.5)pfu Influenza A/Mem71 (H3N1)
      or a control preparation. Mice were subjected to methacholine (MCh) challenge at
      3-4 days post-infection during the peak of cellular inflammation. Inflammation,
      protein content and cytokines (TNF-alpha and MIP-2) were assessed in
      bronchoalveolar lavage fluid. Influenza-infected mice had a heightened
      responsiveness to MCh, increased cellular inflammation, increased protein leak
      and altered cytokine production, none of which were influenced by the absence of
      NE. These data demonstrate that NE does not modulate neutrophil recruitment,
      cytokine production, epithelial permeability or responsiveness to
      bronchoconstricting agents during acute influenza infection in mice.

PMID- 20696286
TI  - Do Russia and Eastern Europe need GM plants?
AB  - Russia, Ukraine and Kazakhstan are the leading agricultural producers, especially
      for potato, sugar beet and sunflower. The cumulative effect of adverse climatic
      conditions, high weediness and losses related to viruses and pests (without any
      insecticide and herbicide treatments) led to losses amounting to 40-80% of
      potential production in the Russian Federation and other mentioned countries. We
      have used new biotechnology methods to obtain several crops (potato, sugar beet,
      sunflower and others) tolerant to abiotic and biotic stresses. For the first time
      - on the basis of domestic varieties bred by Russian scientists - GM potato
      varieties have been obtained, resistant to Colorado beetle. These GM potato
      varieties were recognised as being as safe as traditional ones and have been
      registered for food use. Using this technology, new biotechnological sugar beet
      lines tolerant to herbicides were also obtained.

PMID- 20696287
TI  - AMP kinase acts as a negative regulator of RANKL in the differentiation of
      osteoclasts.
AB  - INTRODUCTION: AMP-activated protein kinase (AMPK) has been reported to stimulate
      differentiation and proliferation of osteoblasts, but the role of AMPK in the
      physiology of osteoclasts has not been investigated. METHOD: Osteoclasts were
      differentiated from mouse BMMphis. TRAP-positive multinucleated cells were
      considered to be osteoclasts using TRAP staining, and resorption area was
      determined by incubation of cells on dentine discs. Signaling pathways were
      investigated using Western blotting and RT-PCR. RESULTS: RANKL induced
      phosphorylation/activation of AMPK-alpha in BMMphis and stimulated formation of
      TRAP-positive multinucleated cells. Pharmacological inhibition of AMPK with
      compound C and siRNA-mediated knockdown of AMPK-alpha1, the predominant alpha
      subunit isoform in BMMphis, increased RANKL-induced formation of TRAP-positive
      multinucleated cells and bone resorption via activation of the downstream
      signaling elements p38, JNK, NF-kappaB, Akt, CREB, c-Fos, and NFATc1. STO-609, an
      inhibitor of CaMKK, completely blocked the RANKL-induced activation of AMPK
      alpha, but KN-93, an inhibitor of CaMK, did not. siRNA-mediated TAK1 knockdown
      also blocked RANKL-induced activation of AMPK-alpha. The AMPK activators
      metformin, (-)-epigallocatechin-3-gallate, berberine, resveratrol, and alpha
      lipoic acid dose-dependently suppressed formation of TRAP-positive multinucleated
      cells and bone resorption. CONCLUSION: AMPK negatively regulates RANKL, possibly
      by acting through CaMKK and TAK1. Thus, the development of AMPK activators may be
      a useful strategy for inhibiting the resorption of bone that is stimulated under
      RANKL-activated conditions.

PMID- 20696288
TI  - Modeling human osteosarcoma in the mouse: From bedside to bench.
AB  - Osteosarcoma (OS) is the most common primary tumour of bone, occurring
      predominantly in the second decade of life. High-dose cytotoxic chemotherapy and
      surgical resection have improved prognosis, with long-term survival for patients
      with localized (non-metastatic) disease approaching 70%. At presentation
      approximately 20% of patients have metastases and almost all patients with
      recurrent OS have metastatic disease and cure rates for patients with metastatic
      or recurrent disease remain poor (<20% survival). Over the past 20 years,
      considerable progress has been made in the understanding of OS pathogenesis, yet
      these insights have not translated into substantial therapeutic advances and
      clinical outcomes. Further progress is essential in order to develop molecularly
      based therapies that target both primary lesions as well as metastatic disease.
      The increasing sophistication with which gene expression can be modulated in the
      mouse, both positively and negatively in addition to temporally, has allowed for
      the recent generation of more faithful OS models than have previously been
      available. These murine OS models can recapitulate all aspects of the disease
      process, from initiation and establishment to invasion and dissemination to
      distant sites. The development and utilisation of murine models that faithfully
      recapitulate human osteosarcoma, complementing existing approaches using human
      and canine disease, holds significant promise in furthering our understanding of
      the genetic basis of the disease and, more critically, in advancing pre-clinical
      studies aimed at the rational development and trialing of new therapeutic
      approaches.

PMID- 20696289
TI  - Genetic self knowledge and the future of epidemiologic confounding.
AB  - Prior work has considered how our genetic knowledge might allow for personalized
      medicine. This commentary explores the reverse question of what personalized
      genetic medicine might do to our research process, not only in genetics, but in
      epidemiology more generally.

PMID- 20696291
TI  - FKBP10 and Bruck syndrome: phenotypic heterogeneity or call for reclassification?

PMID- 20696290
TI  - Detecting heteroplasmy from high-throughput sequencing of complete human
      mitochondrial DNA genomes.
AB  - Heteroplasmy, the existence of multiple mtDNA types within an individual, has
      been previously detected by using mostly indirect methods and focusing largely on
      just the hypervariable segments of the control region. Next-generation sequencing
      technologies should enable studies of heteroplasmy across the entire mtDNA genome
      at much higher resolution, because many independent reads are generated for each
      position. However, the higher error rate associated with these technologies must
      be taken into consideration to avoid false detection of heteroplasmy. We used
      simulations and phiX174 sequence data to design criteria for accurate detection
      of heteroplasmy with the Illumina Genome Analyzer platform, and we used
      artificial mixtures and replicate data to test and refine the criteria. We then
      applied these criteria to mtDNA sequence reads for 131 individuals from five
      Eurasian populations that had been generated via a parallel tagged approach. We
      identified 37 heteroplasmies at 10% frequency or higher at 34 sites in 32
      individuals. The mutational spectrum does not differ between heteroplasmic
      mutations and polymorphisms in the same individuals, but the relative mutation
      rate at heteroplasmic mutations is significantly higher than that estimated for
      all mutable sites in the human mtDNA genome. Moreover, there is also a
      significant excess of nonsynonymous mutations observed among heteroplasmies,
      compared to polymorphism data from the same individuals. Both mutation-drift and
      negative selection influence the fate of heteroplasmies to determine the
      polymorphism spectrum in humans. With appropriate criteria for avoiding false
      positives due to sequencing errors, next-generation technologies can provide
      novel insights into genome-wide aspects of mtDNA heteroplasmy.

PMID- 20696293
TI  - Into the sunset.

PMID- 20696294
TI  - Cardiac drugs used in cross-sectional cardiac imaging: what the radiologist needs
      to know.
AB  - The demand for cross-sectional imaging of the heart is increasing dramatically
      and in many centres these imaging techniques are being performed by radiologists.
      Although radiologists are familiar with the computed tomography (CT) and magnetic
      resonance imaging (MRI) techniques to generate high-quality images and with using
      contrast agents, many are less familiar with administering the drugs necessary to
      perform CT coronary angiography and cardiac MR reliably. The aim of this article
      is to give an overview of the indications for and the contraindications to
      administering cardiac drugs in cross-sectional imaging departments. We also
      outline the complications that may be encountered and provide advice on how to
      treat these complications when they occur.

PMID- 20696295
TI  - Cardiac and pericardial calcifications on chest radiographs.
AB  - Many types of cardiac and pericardial calcifications identified on chest
      radiographs can be recognized and distinguished based on characteristic locations
      and appearances. The purpose of this review is to emphasize the importance of
      detecting cardiac and pericardial calcifications on chest radiographs, and to
      illustrate and describe the various types of calcifications that may be
      encountered and how they may be differentiated from one another. Each type of
      cardiac and pericardial calcification is discussed, its location and appearance
      described, and its significance explained. Recognizing and understanding these
      calcifications is important as they are often encountered in daily practice and
      play an important role in patient care.

PMID- 20696296
TI  - Distribution of abdominal adipose tissue as a predictor of hepatic steatosis
      assessed by MRI.
AB  - AIM: To evaluate the relationship between the distribution of visceral and
      subcutaneous adipose tissue and hepatic steatosis assessed using magnetic
      resonance imaging (MRI). MATERIALS AND METHODS: One T1-weighted, in-/out-of
      phase, single-section sequence at the L3/L4 level and one multi-echo gradient MRI
      (MGRE) sequence were performed on 65 patients [19 females and 46 males; age 57+/
      9.5 years; body mass index (BMI) 31+/-5.1kg/m(2)]. Visceral adipose tissue (VAT),
      subcutaneous adipose tissue (SAT) surfaces, and hepatic steatosis were
      automatically calculated using in-house software. Weight, height, BMI, waist
      circumference, hip circumference, and waist:hip ratio were recorded. The
      probability of having a steatosis greater than 10% on MRI was evaluated by
      receiver operating characteristic (ROC) curves. RESULTS: The anthropometric
      parameter best correlated to hepatic steatosis was the waist-to-hip ratio
      (r=0.301). VAT and proportion of VAT were correlated to liver fat content
      (r=0.307 and r=0.249, respectively). No significant correlations were found for
      BMI, hip circumference, and SAT. The area under the receiver operating
      characteristics (AUROCs) for the relationship between liver steatosis and BMI,
      waist circumference, waist:hip ratio, VAT surface, and proportion of VAT, were
      respectively 0.52, 0.63, 0.71, 0.73 and 0.75. CONCLUSION: Adipose tissue
      distribution is more relevant than total fat mass when assessing the possibility
      of liver steatosis in overweight patients.

PMID- 20696297
TI  - Characterization of liver metastases: the efficacy of biphasic magnetic resonance
      imaging with ferucarbotran-enhancement.
AB  - AIM: To retrospectively evaluate the efficacy of biphasic magnetic resonance
      imaging (MRI) of the liver with ferucarbotran-enhancement for the
      characterization of hepatic metastases. MATERIALS AND METHODS: Thirty-six
      patients underwent MRI of the liver with separate acquisition of double-contrast
      enhancement consisting of gadolinium and ferucarbotran. A total of 106 focal
      hepatic lesions (51 metastases, 31 cysts, 23 haemangiomas, and one eosinophilic
      abscess) were included. Two sets of MRI were analysed: (1) ferucarbotran set:
      ferucarbotran-enhanced T1-weighted (T1W) dynamic imaging combined with
      ferucarbotran-enhanced T2*-weighted (T2*W) delayed imaging and (2) double set:
      gadolinium-enhanced T1W dynamic imaging combined with ferucarbotran-enhanced T2*W
      delayed imaging. The diagnostic accuracy of the two sets was evaluated using
      alternative free-response receiver operating characteristic curve analysis.
      Sensitivity and specificity were compared using the McNemar test. The enhancement
      pattern of focal hepatic lesions was analysed on gadolinium and ferucarbotran
      enhanced T1W dynamic imaging. RESULTS: There was no significant difference in the
      accuracy of characterizing hepatic metastases between the two sets. Sensitivity
      and specificity were not significantly different between the sets (p>0.05).
      Peripheral rim enhancement was exhibited in 57% of metastatic lesions on
      ferucarbotran-enhanced T1W dynamic imaging. The majority (96%) of hepatic
      haemangiomas demonstrated typical peripheral nodular enhancement with progression
      on ferucarbotran-enhanced T1W dynamic imaging and were easily differentiated from
      metastases. CONCLUSION: Biphasic MRI of the liver with ferucarbotran-enhancement
      alone provided comparable diagnostic efficacy to double-contrast MRI for the
      characterization of hepatic metastases.

PMID- 20696298
TI  - Diagnostic precision of CT in local staging of colon cancers: a meta-analysis.
AB  - AIM: To determine the accuracy of computed tomography (CT) in detecting disease
      with invasion beyond the muscularis propria (MP) and malignant lymph nodes.
      MATERIALS AND METHODS: A literature search of Ovid, Embase, the Cochrane
      database, and Medline using Pubmed, Google Scholar and Vivisimo search engines
      was performed to identify studies reporting on the accuracy of CT to predict the
      staging of colonic tumours. Publication bias was demonstrated by Funnel plots.
      The sensitivity, specificity, and diagnostic odds ratio (DOR) were calculated
      using a bivariate random effects model and hierarchical summary operating curves
      (HSROC) were generated. RESULTS: Nineteen studies fulfilled all the necessary
      inclusion criteria. The pooled sensitivity, specificity, DOR for detection of
      tumour invasion were 86% (95% CI: 78-92%); 78% (95% CI: 71-84%); 22.4 (95% CI:
      11.9-42.4). Similarly, the values for nodal detection were 70% (95% CI: 63-73%);
      78% (95% CI: 73-82%); 8.1(95% CI: 4.7-14.1). In the subgroup analysis, the best
      results were obtained in studies utilizing multidetector CT (MDCT). CONCLUSION:
      Preoperative staging CT accurately distinguishes between tumours confined to the
      bowel wall and those invading beyond the MP; however, it is significantly poorer
      at identifying nodal status. MDCT provides the best results.

PMID- 20696299
TI  - A retrospective analysis of selective internal radiation therapy (SIRT) with
      yttrium-90 microspheres in patients with unresectable hepatic malignancies.
AB  - AIM: To evaluate the efficacy and safety of selective internal radiation therapy
      (SIRT). MATERIALS AND METHODS: A retrospective analysis was undertaken of all
      patients who underwent SIRT at a single institution. Diagnostic and therapeutic
      angiograms, computed tomography (CT) images, positron-emission tomography (PET)
      images, and planar isotope images were analysed. The response to SIRT was
      analysed using radiological data and tumour markers. Overall survival,
      complications, and side effects of SIRT were also analysed. RESULTS: The initial
      12 patients were included on an intention-to-treat basis, between 21/09/2005 and
      07/05/2008. All patients had advanced disease and multiple prior courses of
      chemotherapy. One patient did not receive yttrium-90 due to complex vascular
      anatomy; the remaining 11 patients underwent 13 SIRT treatment episodes following
      work-up angiography. A response was seen using PET in 80% of patients. Using CT,
      the response of the tumour to therapy in the treated hepatic segments
      demonstrated a 20% partial response, stable disease in 50%, and progressive
      disease in 30%. Estimated median survival was 229 days, with 64% of patients
      still alive at the time of writing. No major complications were observed,
      although 82% of patients experienced side-effects following SIRT, mainly nausea,
      vomiting, and abdominal pain. CONCLUSIONS: There have been no complications in
      the 12 SIRT patients. Tumour response was seen in four out of five patients who
      underwent PET. Objective CT response rates were mixed and are perhaps partially
      explained by advanced disease and limitations of using measurements to assess
      response. This complex and potentially hazardous service has been successfully
      and safely established.

PMID- 20696300
TI  - Correlation between kinking and coiling of the carotid arteries as assessed using
      MDCTA with symptoms and degree of stenosis.
AB  - AIM: To evaluate whether the presence of kinking and coiling of the carotid
      arteries is associated with symptoms and an increased degree of carotid artery
      stenosis. MATERIALS AND METHODS: One hundred and fifty-three consecutive patients
      examined using multidetector-row computed tomography angiography (MDCTA) were
      studied retrospectively. The arterial phase was obtained by injecting 4-6ml/s of
      contrast material. A total of 306 carotid arteries were assessed for the presence
      of tortuosity. The degree of carotid artery stenosis was measured according to
      North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria.
      Logistic regression analysis was performed to determine whether an independent
      association existed between the presence of vessel tortuosity, symptoms, and the
      degree of carotid artery stenosis. RESULTS: Kinking was detected on 37 occasions
      (12.1%) and coiling on 20 occasions (6.5%). Using Yates's corrected chi-square
      test, an association between kinking and symptoms (p=0.002) was observed, but not
      between coiling and symptoms (p=0.31). Logistic regression confirmed that the
      strongest association was present between stenosis degree and symptoms (p=0.001),
      but kinking (p=0.009) and age (p=0.001) were also significantly associated with
      symptoms. A Mann-Whitney test did not demonstrate correlation between coiling
      (p=0.16) or kinking (p=0.22) and increased degree of carotid artery stenosis.
      CONCLUSION: The results suggest that kinking may be associated with symptoms,
      whereas coiling does not appear to be associated with symptoms. The degree of
      carotid artery stenosis severity is not related to the presence of vessel
      tortuosity.

PMID- 20696301
TI  - CT findings in autoimmune pancreatitis: assessment using multiphase contrast
      enhanced multisection CT.
AB  - AIM: To assess the spectrum of findings using multiphase contrast-enhanced
      computed tomography (CT) in patients with autoimmune pancreatitis (AIP).
      MATERIALS AND METHODS: Fifty patients (four female and 46 male, mean age 65
      years) were retrospectively identified from consecutive patients with abnormal CT
      findings of the pancreas and negative work-up for known causes. These patients
      had at least one finding supporting the diagnosis of AIP: serological
      abnormality, histopathological abnormality, or response to steroid. Two
      radiologists evaluated multiphase contrast-enhanced CT images in consensus.
      RESULTS: The pancreas showed diffuse enlargement (n=16; 32%), focal enlargement
      (n=18; 36%), or no enlargement (n=16; 32%). Forty-nine (98%) patients showed
      abnormal contrast enhancement in the affected pancreatic parenchyma, including
      hypoattenuation during the pancreatic phase (n=45; 90%) and hyperattenuation
      during the delayed phase (n=39; 87%). The following findings were also seen in
      the pancreas: a capsule-like rim (n=24; 48%); no visualization of the main
      pancreatic duct lumen (n=48; 96%); ductal enhancement (n=26; 52%); upstream
      dilatation of the main pancreatic duct (n=27; 54%); upstream atrophy of the
      pancreatic parenchyma (n=27; 54%); calcification (n=7; 14%); and cysts (n=5;
      10%). Forty-two (84%) patients showed one or more of the following
      extrapancreatic findings: biliary duct or gallbladder abnormality (n=40; 80%);
      peripancreatic (n=8; 16%) or para-aortic (n=10; 20%) soft-tissue proliferation;
      and renal involvement (n=15; 30%). CONCLUSION: Patients with AIP presented with a
      variety of CT findings in the pancreas and the extrapancreatic organs. The
      present study highlights pancreatic ductal enhancement in a subset of patients
      with AIP.

PMID- 20696302
TI  - Duplex sonography in the planning and evaluation of arteriovenous fistulae for
      haemodialysis.
AB  - This paper describes how to perform duplex sonography in the planning and
      evaluation of arteriovenous fistulae in haemodialysis patients, discusses its
      roles in these settings, and presents a review of commonly encountered
      complications.

PMID- 20696303
TI  - Multi-technique imaging of sarcoidosis.
AB  - Sarcoidosis is a multisystem granulomatous disorder of unknown aetiology. The
      diagnosis is suggested on the basis of wide ranging clinical and radiological
      manifestations, and is supported by the histological demonstration of non
      caseating granulomas in affected tissues. This review highlights the multisystem
      radiological features of the disease across a variety of imaging methods
      including multidetector computed tomography (CT), magnetic resonance imaging
      (MRI) as well as functional radionuclide techniques, particularly 2-[(18)F]
      fluoro-2-deoxy-d-glucose (FDG) positron emission tomography/computed tomography
      (PET/CT). It is important for the radiologist to be aware of the varied
      radiological manifestations of sarcoidosis in order to recognize and suggest the
      diagnosis in the appropriate clinical setting.

PMID- 20696304
TI  - Jejunal leiomyoma with foreign body abscess: computed tomographic findings with
      pathological correlation.

PMID- 20696305
TI  - Sporadic lymphangioleiomyomatosis with multiple atypical adenomatoid hyperplasia:
      differentiation from multifocal micronodular pneumocyte hyperplasia.

PMID- 20696307
TI  - Re: non-invasive evaluation of liver cirrhosis using ultrasound.

PMID- 20696309
TI  - Re: tuberculosis in the head and neck--a forgotten differential diagnosis.

PMID- 20696310
TI  - Re: Reversed halo sign: nodular wall as criterion for differentiation between
      cryptogenic organizing pneumonia and active granulomatous diseases.

PMID- 20696311
TI  - Recent advances in Parkinson's disease: basic research. Preface.

PMID- 20696312
TI  - Identifying PD-causing genes and genetic susceptibility factors: current
      approaches and future prospects.
AB  - Over the last years, a plethora of genetic findings have completely changed our
      views on the aetiology of Parkinson's disease (PD). Linkage studies and
      positional cloning strategies have identified mutations in a growing number of
      genes which cause monogenic autosomal-dominant or autosomal-recessive forms of
      the disorder. While these Mendelian forms of PD are relatively rare, high
      throughput genotyping and sequencing technologies have more recently provided
      evidence that low-penetrance variants in at least some of these genes also play a
      direct role in the aetiology of the common sporadic disease. In addition, rare
      variants in other genes, such as the Gaucher's disease-associated
      glucocerebrosidase A, have also been found to be important risk factors at least
      in subgroups of patients. Thus, an increasingly complex network of genes
      contributing in different ways to disease risk and progression is emerging. These
      findings provide the 'genetic entry points' to identify molecular targets and
      readouts necessary to design rational disease-modifying treatments.

PMID- 20696315
TI  - What causes the death of dopaminergic neurons in Parkinson's disease?
AB  - The factors governing neuronal loss in Parkinson's disease (PD) are the subject
      of continuing speculation and experimental study. In recent years, factors that
      act on most or all cell types (pan-cellular factors), particularly genetic
      mutations and environmental toxins, have dominated public discussions of disease
      aetiology. Although there is compelling evidence supporting an association
      between disease risk and these factors, the pattern of neuronal pathology and
      cell loss is difficult to explain without cell-specific factors. This chapter
      focuses on recent studies showing that the neurons at greatest risk in PD-
      substantia nigra pars compacta (SNc) dopamine (DA) neurons--have a distinctive
      physiological phenotype that could contribute to their vulnerability. The opening
      of L-type calcium channels during autonomous pacemaking results in sustained
      calcium entry into the cytoplasm of SNc DA neurons, resulting in elevated
      mitochondrial oxidant stress and susceptibility to toxins used to create animal
      models of PD. This cell-specific stress could increase the negative consequences
      of pan-cellular factors that broadly challenge either mitochondrial or
      proteostatic competence. The availability of well-tolerated, orally deliverable
      antagonists for L-type calcium channels points to a novel neuroprotective
      strategy that could complement current attempts to boost mitochondrial function
      in the early stages of the disease.

PMID- 20696314
TI  - Unravelling the role of defective genes.
AB  - Several genes that cause familial forms of Parkinson's disease (PD) or similar
      disorders have been found in recent years. The aim of this review is to cover two
      broad aspects of the logic of genetics. The first aspect is the recognition that
      PD can have a genetic basis, either for Mendelian families where genes can be
      identified because mutations segregate with disease or in populations where more
      common variants are associated with disease. There are several causal genes for
      both dominant and recessive forms of parkinsonism, some of which overlap with
      sporadic PD and some of which have more complex phenotypes. Several of the
      dominant loci have also been reliably identified as risk factors for sporadic PD.
      The second topic is how the study of multiple mutations in any given gene can
      help understand the role that the protein under investigation plays in PD.
      Examples will be given of both recessive and dominant genes for parkinsonism,
      showing how the analysis of multiple gene mutations can be a powerful approach
      for dissecting out which function(s) are important for the disease process.

PMID- 20696313
TI  - The impact of genetic research on our understanding of Parkinson's disease.
AB  - Until recently, genetics was thought to play a minor role in the development of
      Parkinson's disease (PD). Over the last decade, a number of genes that
      definitively cause PD have been identified, which has led to the generation of
      disease models based on pathogenic gene variants that recapitulate many features
      of the disease. These genetic studies have provided novel insight into potential
      mechanisms underlying the aetiology of PD. This chapter will provide a profile of
      the genes conclusively linked to PD and will outline the mechanisms of PD
      pathogenesis implicated by genetic studies. Mitochondrial dysfunction, oxidative
      stress and impaired ubiquitin-proteasome system function are disease mechanisms
      that are particularly well supported by genetic studies and are therefore the
      focus of this chapter.

PMID- 20696317
TI  - Control of mitochondrial integrity in Parkinson's disease.
AB  - Parkinson's disease (PD) is the most common neurodegenerative movement disorder
      associated with a loss of dopaminergic neurons. The role of mitochondria in the
      aetiology of PD has been questioned for decades, mostly from the perspective of
      bioenergetic failure. For decades, a deficit in mitochondrial respiration was
      thought to be a key factor in PD neurodegeneration. However, excluding a few
      exceptions where a clinical picture of parkinsonism is associated with a
      mitochondrial DNA mutation, preclinical and clinical studies have failed to
      identify any genetic mutations in the genes encoding for the electron transport
      chain complexes in PD patients. More recently, it has been discovered that
      mutations in the genes encoding for Parkin, PINK1 (PTEN-induced putative kinase
      1) and DJ-1 are associated with familial forms of PD and with mitochondrial
      alterations, including morphological abnormalities. These results have led many
      researchers to revisit the question of mitochondrial biology as a primary
      mechanism in PD pathogenesis, this time from an angle of perturbation in
      mitochondrial dynamics and not from the angle of a deficit in respiration.

PMID- 20696316
TI  - Intracellular signalling pathways in dopamine cell death and axonal degeneration.
AB  - The pathways of programmed cell death (PCD) are now understood in extraordinary
      detail at the molecular level. Although much evidence suggests that they are
      likely to play a role in Parkinson's disease (PD), the precise nature of that
      role remains unknown. Two pathways of cell death that are especially well
      characterized are cyclin-dependent kinase 5-mediated phosphorylation of myocyte
      enhancer factor 2 and the mitogen-activated protein kinase signalling cascade.
      Although blockade of these pathways in animals has achieved a truly remarkable
      degree of neuroprotection of the neuron cell soma, it has not achieved protection
      of axons. Thus, there is a need to explore beyond the canonical pathways of PCD
      and investigate mechanisms of axon destruction. We also need to move beyond the
      narrow classic concept that the mechanisms of PCD are activated exclusively
      'downstream', following cellular injury. Studies in the genetics of PD suggest
      that in some forms of the disease, activation may be an early 'upstream' event.
      Additionally, recent observations suggest that cell death in some contexts may
      not be initiated by injury, but instead by a failure of intrinsic cell survival
      signalling. These new points of view offer new opportunities for molecular
      targeting.

PMID- 20696318
TI  - Role of post-translational modifications in modulating the structure, function
      and toxicity of alpha-synuclein: implications for Parkinson's disease
      pathogenesis and therapies.
AB  - A better understanding of the molecular and cellular determinants that influence
      the pathology of Parkinson's disease (PD) is essential for developing effective
      diagnostic, preventative and therapeutic strategies to treat this devastating
      disease. A number of post-translational modifications to alpha-syn are present
      within the Lewy bodies in the brains of affected patients and transgenic models
      of PD and related disorders. However, whether disease-associated alpha-syn post
      translational modifications promote or inhibit alpha-syn aggregation and
      neurotoxicity in vivo remains unknown. Herein, we summarize and discuss the major
      disease-associated post-translational modifications (phosphorylation, truncation
      and ubiquitination) and present our current understanding of the effect of these
      modifications on alpha-syn aggregation and toxicity. Elucidating the molecular
      mechanisms underlying post-translation modifications of alpha-syn and the
      consequences of such modifications on the biochemical, structural, aggregation
      and toxic properties of the protein is essential for unravelling the molecular
      basis of its function(s) in health and disease. Furthermore, the identification
      of the natural enzymes involved in regulating the post-translational
      modifications of alpha-synuclein will yield novel and more tractable therapeutic
      targets to treat PD and related synucleinopathies.

PMID- 20696320
TI  - Assemblies of glutamate receptor subunits with post-synaptic density proteins and
      their alterations in Parkinson's disease.
AB  - N-methyl-D-aspartate (NMDA) receptors have been implicated as a mediator of
      neuronal injury associated with many neurological disorders including ischemia,
      epilepsy, brain trauma, dementia and neurodegenerative disorders such as
      Parkinson's disease (PD) and Alzheimer's disease. To this, non-selective NMDA
      receptor antagonists have been tried and have been shown to be effective in many
      experimental animal models of disease, and some of these compounds have moved
      into clinical trials. However, the initial enthusiasm for this approach has
      waned, because the therapeutic index for most NMDA antagonists is quite poor,
      with significant adverse effects at clinically effective doses, thus limiting
      their utility. More recently, the concept that the exact pathways downstream NMDA
      receptor activation could represent a key variable element among neurological
      disorders has been put forward. In particular, variations in NMDA receptor
      subunit composition could be important in different disorders, both in the
      pathophysiological mechanisms of cell death and in the application of specific
      symptomatic therapies. As to PD, NMDA receptor complex has been shown to be
      altered in experimental models of parkinsonism and in PD in humans. Further, it
      has become increasingly evident that the NMDA receptor complex is intimately
      involved in the regulation of corticostriatal long-term potentiation, which is
      altered in experimental parkinsonism. The following sections will examine the
      modifications of specific NMDA receptor subunits as well as post-synaptic
      associated signalling complex including kinases and scaffolding proteins in
      experimental parkinsonism. These findings may allow the identification of
      specific molecular targets whose pharmacological or genetic manipulation might
      lead to innovative therapies for PD.

PMID- 20696319
TI  - The role of dopamine in modulating the structure and function of striatal
      circuits.
AB  - Dopamine (DA) is a key regulator of action selection and associative learning.
      The striatum has long been thought to be a major locus of DA action in this
      process. Although all striatal cell types express G protein-coupled receptors for
      DA, the effects of DA on principal medium spiny neurons (MSNs) understandably
      have received the most attention. In the two principal classes of MSN, DA
      receptor expression diverges, with striatonigral MSNs robustly expressing D(1)
      receptors and striatopallidal MSNs expressing D(2) receptors. In the last couple
      of years, our understanding of how these receptors and the intracellular
      signalling cascades that they couple to modulate dendritic physiology and
      synaptic plasticity has rapidly expanded, fuelled in large measure by the
      development of new optical and genetic tools. These tools also have enabled a
      rapid expansion of our understanding of the striatal adaptations in models of
      Parkinson's disease. This chapter highlights some of the major advances in these
      areas.

PMID- 20696323
TI  - Effects of GPi and STN inactivation on physiological, motor, cognitive and
      motivational processes in animal models of Parkinson's disease.
AB  - Loss of the dopaminergic input to the striatum, characterizing Parkinson's
      disease, leads to the hyper-activity of two key nuclei of the basal ganglia (BG):
      the subthalamic nucleus (STN) and the internal segment of the globus pallidus
      (GPi). The anatomo-physiological organization of the BG and their output
      suggested that interfering with such hyper-activity could restore motor function
      and improve parkinsonism. Several animal models in rodents and primates, as well
      as clinical studies and neurosurgical treatments, have confirmed such hypothesis.
      This chapter will review the physiological and behavioural data obtained by
      inactivating the GPi or the STN by means of lesions, pharmacological approaches
      and deep brain stimulation. The consequences of these treatments will be examined
      at levels ranging from cellular to complex behavioural changes. Some of this
      experimental evidence suggested new and effective clinical treatments for PD,
      which are now routinely used worldwide. However, further studies are necessary to
      better understand the consequences of GPi and STN manipulation especially at the
      cognitive level in order to improve functional neurosurgical treatments for
      Parkinson's disease by minimizing risks of side-effects.

PMID- 20696324
TI  - Computational physiology of the basal ganglia in Parkinson's disease.
AB  - The normal activity of basal ganglia neurons is characterized by Poisson-like
      (random) firing patterns. Correlations between neurons of the same structure are
      weak or non-existent. By contrast, synchronous oscillations are commonly found in
      the basal ganglia of human patients and animal models of Parkinson's disease. The
      frequency of these oscillations is often similar to that of the parkinsonian
      tremor, but their role in generating the tremor or other parkinsonian symptoms is
      still under debate. The tremor is intermittent and does not appear in all human
      patients. Similarly, primate models tend to develop tremor as a function of
      species of monkey. African green (vervet) monkeys usually demonstrate a high
      amplitude, low-frequency (4-7Hz) tremor beyond their akinesia and bradykinesia,
      whereas macaques tend to be akinetic rigid and rarely demonstrate a low-amplitude
      high-frequency (10-12Hz) action-postural tremor. We took advantage of this fact
      and studied the appearance of the synchronicity and oscillations in six monkeys,
      three vervets and three macaques, before and after 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP) systemic treatment and induction of parkinsonism.
      Multiple extracellular recordings were conducted in the primary motor cortex of
      two monkeys and in the globus pallidus (GP) of all six monkeys. All the monkeys
      became akinetic and bradykinetic as a result of the MPTP treatment, but only
      vervets demonstrated prolonged episodes of low-frequency (4-6Hz) tremor, whereas
      macaques were non-tremulous. The GP population exhibited approximately 5Hz
      oscillatory activity in all six monkeys, whereas approximately 10Hz neural
      oscillations were only detected in the tremulous monkeys. The activity of the
      cortical neurons became strongly oscillatory at approximately 10Hz in one of
      these monkeys, but not the other, although both were tremulous and exhibited
      comparable pallidal oscillatory activity. Finally, synchronous oscillations, when
      present, were centred around the higher frequencies of oscillations. These
      findings suggest that there is a correlation between high-frequency GP neural
      oscillations and tremor. Furthermore, these pallidal 10Hz oscillations are
      probably transferred to the periphery through cortical and brainstem pathways.

PMID- 20696326
TI  - Editorial comment.

PMID- 20696321
TI  - Pathophysiological roles for purines: adenosine, caffeine and urate.
AB  - The motor symptoms of Parkinson's disease (PD) are primarily due to the
      degeneration of the dopaminergic neurons in the nigrostriatal pathway. However,
      several other brain areas and neurotransmitters other than dopamine such as
      noradrenaline, 5-hydroxytryptamine and acetylcholine are affected in the disease.
      Moreover, adenosine because of the extensive interaction of its receptors with
      the dopaminergic system has been implicated in the pathophysiology of the
      disease. Based on the involvement of these non-dopaminergic neurotransmitters in
      PD and the sometimes severe adverse effects that limit the mainstay use of
      dopamine-based anti-parkinsonian treatments, recent assessments have called for a
      broadening of therapeutic options beyond the traditional dopaminergic drug
      arsenal. In this review we describe the interactions between dopamine and
      adenosine receptors that underpin the pre-clinical and clinical rationale for
      pursuing adenosine A(2A) receptor antagonists as symptomatic and potentially
      neuroprotective treatment of PD. The review will pay particular attention to
      recent results regarding specific A(2A) receptor-receptor interactions and recent
      findings identifying urate, the end product of purine metabolism, as a novel
      prognostic biomarker and candidate neuroprotectant in PD.

PMID- 20696325
TI  - Neurocomputational models of motor and cognitive deficits in Parkinson's disease.
AB  - We review the contributions of biologically constrained computational models to
      our understanding of motor and cognitive deficits in Parkinson's disease (PD).
      The loss of dopaminergic neurons innervating the striatum in PD, and the well
      established role of dopamine (DA) in reinforcement learning (RL), enable neural
      network models of the basal ganglia (BG) to derive concrete and testable
      predictions. We focus in this review on one simple underlying principle - the
      notion that reduced DA increases activity and causes long-term potentiation in
      the indirect pathway of the BG. We show how this theory can provide a unified
      account of diverse and seemingly unrelated phenomena in PD including progressive
      motor degeneration as well as cognitive deficits in RL, decision making and
      working memory. DA replacement therapy and deep brain stimulation can alleviate
      some aspects of these impairments, but can actually introduce negative effects
      such as motor dyskinesias and cognitive impulsivity. We discuss these treatment
      effects in terms of modulation of specific mechanisms within the computational
      framework. In addition, we review neurocomputational interpretations of increased
      impulsivity in the face of response conflict in patients with deep-brain
      stimulation.

PMID- 20696322
TI  - Maladaptive striatal plasticity in L-DOPA-induced dyskinesia.
AB  - Dopamine (DA) replacement therapy with l-DOPA remains the most effective
      treatment for Parkinson's disease, but causes dyskinesia (abnormal involuntary
      movements) in the vast majority of the patients. The basic mechanisms of l-DOPA
      induced dyskinesia (LID) have become the object of intense research focusing on
      neurochemical and molecular adaptations in the striatum. Here we review this vast
      literature and highlight trends that converge into a unifying pathophysiological
      interpretation. We propose that the core molecular alteration of striatal neurons
      in LID consists in an inability to turn down supersensitive signaling responses
      downstream of DA D1 receptors (where supersensitivity is primarily caused by DA
      denervation). The sustained activation of intracellular signaling pathways
      induced by each dose of l-DOPA leads to abnormal cellular plasticity and high
      bioenergetic expenditure. The over-exploitation of signaling pathways and energy
      reserves during treatment impairs the ability of striatal neurons to dynamically
      gate cortically driven motor commands. LID thus exemplifies a disorder where 'too
      much' molecular plasticity leads to plasticity failure in the striatum.

PMID- 20696328
TI  - Editorial comment.

PMID- 20696331
TI  - Editorial comment.

PMID- 20696330
TI  - Editorial comment.

PMID- 20696333
TI  - Editorial comment.

PMID- 20696335
TI  - Editorial comment.

PMID- 20696338
TI  - Editorial comment.

PMID- 20696339
TI  - Editorial comment.

PMID- 20696341
TI  - Editorial comment.

PMID- 20696343
TI  - Editorial comment.

PMID- 20696344
TI  - Editorial comment.

PMID- 20696345
TI  - Editorial comment.

PMID- 20696348
TI  - Editorial comment.

PMID- 20696350
TI  - Editorial comment.

PMID- 20696351
TI  - Editorial comment.

PMID- 20696353
TI  - Editorial comment.

PMID- 20696355
TI  - Editorial comment.

PMID- 20696356
TI  - In vitro multicompartmental bladder model for assessing blockage of urinary
      catheters: effect of hydrogel coating on dynamics of Proteus mirabilis growth.
AB  - OBJECTIVES: To investigate the effect of a hydrogel coating on the dynamics of
      bacterial growth in laboratory models of the catheterized bladder. Infection of
      the urinary tract by Proteus mirabilis can result in catheter blockage by
      crystalline biofilm, a common complication in patients undergoing long-term
      bladder catheterization. METHODS: Two series of catheters were tested in the
      infected bladder models: test series 1, silicone catheters impregnated with
      triclosan (0.5%, 1%, 4%), or silicone catheters with 0% triclosan impregnated
      with pure solvents and hydrogel coated (based on polyvinylpyrrolidone); and test
      series 2, silicone catheters, hydrogel-coated with hydrogel plus iodine
      (polyvinylpyrrolidone plus iodine) or hydrogel plus polyhexamethylene biguanide.
      Test series 1 was used to detect the influence of triclosan, solvents,
      impregnation time, and the presence of hydrogel coating on the interval to
      catheter blockage by P. mirabilis biofilm. The experiments with test series 2
      focused on the dynamic interaction of the hydrogel coating and biofilm formation.
      The division of the catheterized bladder model into 3 sampling zones brought more
      information about the spatial segregation of the bacterial population. RESULTS:
      The bacteriostatic efficiency of the water-soluble polyhexamethylene biguanide
      and polyvinylpyrrolidone iodine complex was limited to the first hours after
      catheterization. Only catheters containing triclosan resisted encrustation for
      significantly longer (up to >7 days). In contrast, the uncoated and hydrogel
      coated catheters were occluded by day 2. CONCLUSIONS: The hydrogel layer can
      increase aggregation of the planktonic cells and newly nucleated crystals,
      leading to even faster catheter blockage than in the case of uncoated silicone.
      However, the addition of active agents were able to suppress this negative
      effect.

PMID- 20696357
TI  - Re: Steinberg et al.: YouTube as source of prostate cancer information (Urology
      2010;75:619-622).

PMID- 20696359
TI  - Follow-up survey of all participants at the first and second juvenile diabetes
      summer camp in Japan in 1963 and 1964.
AB  - This report documents the status of all 10 participants in the first (1963) and
      second (1964) summer camp in Japan as of 31 December 2008. The eight living
      participants continue to function as adults in society without hemodialysis.

PMID- 20696360
TI  - Targeting educational interventions to clinician's stage of change.
AB  - This before-after mixed-method study assessed the effect of a diabetes education
      and self-efficacy training workshop on clinician knowledge, intention and self
      efficacy. This workshop demonstrated and narrowed a knowledge gap but did not
      change intention or self-efficacy. Neither the intervention nor the measured
      outcomes were targeted to clinicians' stage of change.

PMID- 20696361
TI  - The association between quality of life, depressive symptoms and glycemic control
      in a group of type 2 diabetes patients.
AB  - AIMS: Several studies have demonstrated worse perception of quality of life (QoL)
      among patients with type 2 diabetes mellitus (T2DM). The purpose of our study was
      to assess QoL in a clinical sample of patients with T2DM and its association with
      depressive symptoms and glycemic control. METHODS: One hundred outpatients from a
      sequential sample underwent clinical and psychiatric evaluation. The Problem
      Areas of Diabetes scale (PAID) and the Beck Depression Inventory (BDI) were used
      to assess, respectively, QoL and the presence of overall psychopathology. The
      levels of glycated hemoglobin (HbA1c) were used as the main parameter of glycemic
      control. RESULTS: The perception degree of the QoL related with diabetes was
      associated with the severity of depressive symptoms (r=0.503; p<0.001), but not
      with HbA1c levels (p=0.117). However, the severity of general psychopathology,
      evaluated through the BDI scores, predicted the metabolic control, measured by
      HbA1c levels, among the patients in our sample (r=0.233; p=0.019). CONCLUSIONS:
      In our study, PAID was a valuable tool for the evaluation of QoL in T2DM and the
      screening of depressive symptoms. However, no correlation observed between PAID
      scores and HbA1c levels. Self-perception evaluation of T2DM patient can help to
      identify susceptible subjects to current depression.

PMID- 20696369
TI  - Factors influencing the tensile strength of repaired Achilles tendon: a
      biomechanical experiment study.
AB  - BACKGROUND: Operative treatment has been advocated as the method of choice to
      repair Achilles tendon rupture as surgery results in reduced re-rupture rate and
      faster rehabilitation. Many surgical techniques have been introduced allowing for
      postoperative early motion of the ankle joint. However, it is currently very
      difficult for surgeons to determine the optimal treatment conditions for ruptured
      Achilles tendon with an increasing number of end-to-end suture methods, suture
      materials, and epitenon suture techniques. METHODS: In the present biomechanical
      experiment study based on an orthogonal design, thirty-two New Zealand white
      rabbits received Achilles tendon tenotomy and subsequent operative treatment to
      repair the tendon employing four end-to-end suture methods, four suture
      materials, and four epitenon suture techniques. The tensile strength of the
      repaired Achilles tendon was investigated at four rehabilitation periods, and in
      comparison with the results of another sixteen rabbits with normal Achilles
      tendons. FINDINGS: The end-to-end suture method contributed most to the final
      Achilles tendon tensile strength in addition to rehabilitation period, with the
      highest values occurring with the use of the parachute-like ("Pa" bone) suture
      method. The other two factors, namely, suture material and epitenon suture
      technique, had relatively little influence on the results. INTERPRETATION: The
      parachute-like ("Pa" bone) surgical technique is superior to the other three end
      to-end suture methods, with enhanced tensile strength of the repaired tendon.
      This method allows for postoperative early kinesitherapy of the ankle and knee
      joints. Therefore, this technique is highly recommended in clinical situations
      for treatment of ruptured Achilles tendon.

PMID- 20696370
TI  - The force be with you: a mechanoreceptor channel in proprioception and touch.
AB  - The TRPN1 ion channel has a role in both hearing and bristle mechanosensation in
      fruit flies and in proprioception in nematodes. In this issue of Neuron, two
      papers present evidence that TRPN1 is also required for proprioception in fruit
      fly larvae and that it is a bona fide mechanoreceptor channel for nematode
      feeding behavior.

PMID- 20696371
TI  - Signaling endosomes trigger synapse assembly.
AB  - In this issue of Neuron, Sharma et al. report that target-derived NGF exerts long
      distance control of postsynaptic assembly. A major advance is the discovery that
      TrkA signaling endosomes are retrogradely transported to neuronal dendrites and
      directly trigger the clustering of postsynaptic density proteins.

PMID- 20696372
TI  - Enhanced functions of electrical junctions.
AB  - Electrical synapses and synchrony are nearly synonymous. In this issue of Neuron,
      Vervaeke et al. broaden this longstanding association. They found that in the
      Golgi cell network of the cerebellum, electrical synapses synchronize resting
      activity, and cause surround inhibition and desynchronization in response to
      excitatory input.

PMID- 20696373
TI  - Forward and back: motifs of inhibition in olfactory processing.
AB  - The remarkable performance of the olfactory system in classifying and
      categorizing the complex olfactory environment is built upon several basic neural
      circuit motifs. These include forms of inhibition that may play comparable roles
      in widely divergent species. In this issue of Neuron, a new study by Stokes and
      Isaacson sheds light on how elementary types of inhibition dynamically interact.

PMID- 20696374
TI  - A custody battle for the mind: evidence for extensive imprinting in the brain.
AB  - Relatively few genes (approximately 100) have previously been shown to be
      imprinted such that their expression in progeny derives from either the maternal
      or paternal copy. Two recent studies by Gregg et al. (2010a, 2010b) in Science
      expand this list by an order of magnitude, revealing complex patterns of parent
      of-origin bias in gene expression in the brain that are developmentally and
      regionally restricted, and in many cases, sexually dimorphic.

PMID- 20696375
TI  - Searching for engrams.
AB  - Recent advances in cellular imaging technologies together with novel genetic
      tools have enabled the observation of minute anatomical changes in the intact
      brain. This has elevated the search for physical correlates of memory, one of the
      longstanding questions in modern neurobiology, to a new level. Utilizing these
      new tools, several studies have recently been published pointing to subcellular
      structural changes occurring when the brain stores information about the
      environment. While most of these studies still fall short of investigating memory
      as commonly defined in neuropsychological terms, they are paving the way to more
      refined experiments, which come closer to the identification of true "memory
      traces." In the not too distant future we will be able to observe physical
      changes that occur during learning in the intact animal in real time, leading the
      way to understanding these processes in unprecedented detail.

PMID- 20696376
TI  - The role of the TRP channel NompC in Drosophila larval and adult locomotion.
AB  - The generation of coordinated body movements relies on sensory feedback from
      mechanosensitive proprioceptors. We have found that the proper function of NompC,
      a putative mechanosensitive TRP channel, is not only required for fly locomotion,
      but also crucial for larval crawling. Calcium imaging revealed that NompC is
      required for the activation of two subtypes of sensory neurons during peristaltic
      muscle contractions. Having isolated a full-length nompC cDNA with a protein
      coding sequence larger than previously predicted, we demonstrate its function by
      rescuing locomotion defects in nompC mutants, and further show that antibodies
      against the extended C terminus recognize NompC in chordotonal ciliary tips.
      Moreover, we show that the ankyrin repeats in NompC are required for proper
      localization and function of NompC in vivo and are required for association of
      NompC with microtubules. Taken together, our findings suggest that NompC mediates
      proprioception in locomotion and support its role as a mechanosensitive channel.

PMID- 20696377
TI  - C. elegans TRP family protein TRP-4 is a pore-forming subunit of a native
      mechanotransduction channel.
AB  - Mechanotransduction channels mediate several common sensory modalities such as
      hearing, touch, and proprioception; however, very little is known about the
      molecular identities of these channels. Many TRP family channels have been
      implicated in mechanosensation, but none have been demonstrated to form a
      mechanotransduction channel, raising the question of whether TRP proteins simply
      play indirect roles in mechanosensation. Using Caenorhabditis elegans as a model,
      here we have recorded a mechanosensitive conductance in a ciliated mechanosensory
      neuron in vivo. This conductance develops very rapidly upon mechanical
      stimulation with its latency and activation time constant reaching the range of
      microseconds, consistent with mechanical gating of the conductance. TRP-4, a TRPN
      (NOMPC) subfamily channel, is required for this conductance. Importantly, point
      mutations in the predicted pore region of TRP-4 alter the ion selectivity of the
      conductance. These results indicate that TRP-4 functions as an essential pore
      forming subunit of a native mechanotransduction channel.

PMID- 20696378
TI  - Huntingtin is required for mitotic spindle orientation and mammalian
      neurogenesis.
AB  - Huntingtin is the protein mutated in Huntington's disease, a devastating
      neurodegenerative disorder. We demonstrate here that huntingtin is essential to
      control mitosis. Huntingtin is localized at spindle poles during mitosis. RNAi
      mediated silencing of huntingtin in cells disrupts spindle orientation by
      mislocalizing the p150(Glued) subunit of dynactin, dynein, and the large nuclear
      mitotic apparatus NuMA protein. This leads to increased apoptosis following
      mitosis of adherent cells in vitro. In vivo inactivation of huntingtin by RNAi or
      by ablation of the Hdh gene affects spindle orientation and cell fate of cortical
      progenitors of the ventricular zone in mouse embryos. This function is conserved
      in Drosophila, the specific disruption of Drosophila huntingtin in neuroblast
      precursors leading to spindle misorientation. Moreover, Drosophila huntingtin
      restores spindle misorientation in mammalian cells. These findings reveal an
      unexpected role for huntingtin in dividing cells, with potential important
      implications in health and disease.

PMID- 20696379
TI  - Neural RNA-binding protein Musashi1 controls midline crossing of precerebellar
      neurons through posttranscriptional regulation of Robo3/Rig-1 expression.
AB  - Precisely regulated spatiotemporal gene expression is essential for the
      establishment of neural circuits. In contrast to the increasing evidence for
      transcriptional regulation of axon guidance cues and receptors, the role of
      posttranscriptional regulation in axon guidance, especially in vivo, remains
      poorly characterized. Here, we demonstrate that the expression of Slit receptor
      Robo3/Rig-1, which plays crucial roles in axonal midline crossing, is regulated
      by a neural RNA-binding protein Musashi1 (Msi1). Msi1 binds to Robo3 mRNA through
      RNA recognition motifs and increases the protein level of Robo3 without affecting
      its mRNA level. In Msi1-deficient precerebellar neurons, Robo3 protein, but not
      its mRNA, is dramatically reduced. Moreover, similar to defects in Robo3
      deficient mice, axonal midline crossing and neuronal migration of precerebellar
      neurons are severely impaired in Msi1-deficient mice. Together, these findings
      indicate that Msi1-mediated posttranscriptional regulation of Robo3 controls
      midline crossing of precerebellar neurons.

PMID- 20696380
TI  - Long-distance control of synapse assembly by target-derived NGF.
AB  - We report a role for long-distance retrograde neurotrophin signaling in the
      establishment of synapses in the sympathetic nervous system. Target-derived NGF
      is both necessary and sufficient for formation of postsynaptic specializations on
      dendrites of sympathetic neurons. This, in turn, is a prerequisite for formation
      of presynaptic specializations, but not preganglionic axonal ingrowth from the
      spinal cord into sympathetic ganglia. We also find that NGF-TrkA signaling
      endosomes travel from distal axons to cell bodies and dendrites where they
      promote PSD clustering. Furthermore, the p75 neurotrophin receptor restricts PSD
      formation, suggesting an important role for antagonistic NGF-TrkA and p75
      signaling pathways during retrograde control of synapse establishment. Thus, in
      addition to defining the appropriate number of sympathetic neurons that survive
      the period of developmental cell death, target-derived NGF also exerts control
      over the degree of connectivity between the spinal cord and sympathetic ganglia
      through retrograde control of synapse assembly.

PMID- 20696381
TI  - Rapid desynchronization of an electrically coupled interneuron network with
      sparse excitatory synaptic input.
AB  - Electrical synapses between interneurons contribute to synchronized firing and
      network oscillations in the brain. However, little is known about how such
      networks respond to excitatory synaptic input. To investigate this, we studied
      electrically coupled Golgi cells (GoC) in the cerebellar input layer. We show
      with immunohistochemistry, electron microscopy, and electrophysiology that
      Connexin-36 is necessary for functional gap junctions (GJs) between GoC
      dendrites. In the absence of coincident synaptic input, GoCs synchronize their
      firing. In contrast, sparse, coincident mossy fiber input triggered a mixture of
      excitation and inhibition of GoC firing and spike desynchronization. Inhibition
      is caused by propagation of the spike afterhyperpolarization through GJs. This
      triggers network desynchronization because heterogeneous coupling to surrounding
      cells causes spike-phase dispersion. Detailed network models predict that
      desynchronization is robust, local, and dependent on synaptic input properties.
      Our results show that GJ coupling can be inhibitory and either promote network
      synchronization or trigger rapid network desynchronization depending on the
      synaptic input.

PMID- 20696382
TI  - From dendrite to soma: dynamic routing of inhibition by complementary interneuron
      microcircuits in olfactory cortex.
AB  - Diverse inhibitory pathways shape cortical information processing; however, the
      relevant interneurons recruited by sensory stimuli and how they impact principal
      cells are unclear. Here we show that two major interneuron circuits govern
      dynamic inhibition in space and time within the olfactory cortex. Dendritic
      targeting layer 1 interneurons receive strong input from the olfactory bulb and
      govern early-onset feedforward inhibition. However, this circuit is only
      transiently engaged during bursts of olfactory bulb input. In contrast, somatic
      targeting layer 3 interneurons, recruited exclusively by recurrent excitation
      from pyramidal cells, produce late-onset feedback inhibition. Our results reveal
      two complementary interneuron circuits enforcing widespread inhibition, which
      shifts from the apical dendrites to somata of pyramidal cells during bursts of
      sensory input.

PMID- 20696383
TI  - Selective activation of striatal fast-spiking interneurons during choice
      execution.
AB  - Basal ganglia circuits are essential for the organization and execution of
      voluntary actions. Within the striatum, fast-spiking interneurons (FSIs) are
      thought to tightly regulate the activity of medium-spiny projection neurons
      (MSNs) through feed-forward inhibition, yet few studies have investigated the
      functional contributions of FSIs in behaving animals. We recorded presumed MSNs
      and FSIs together with motor cortex and globus pallidus (GP) neurons, in rats
      performing a simple choice task. MSN activity was widely distributed across the
      task sequence, especially near reward receipt. By contrast, FSIs showed a
      coordinated pulse of increased activity as chosen actions were initiated, in
      conjunction with a sharp decrease in GP activity. Both MSNs and FSIs were
      direction selective, but neighboring MSNs and FSIs showed opposite selectivity.
      Our findings suggest that individual FSIs participate in local striatal
      information processing, but more global disinhibition of FSIs by GP is important
      for initiating chosen actions while suppressing unwanted alternatives.

PMID- 20696384
TI  - A conserved switch in sensory processing prepares developing neocortex for
      vision.
AB  - Developing cortex generates endogenous activity that modulates the formation of
      functional units, but how this activity is altered to support mature function is
      poorly understood. Using recordings from the visual cortex of preterm human
      infants and neonatal rats, we report a "bursting" period of visual responsiveness
      during which the weak retinal output is amplified by endogenous network
      oscillations, enabling a primitive form of vision. This period ends shortly
      before delivery in humans and eye opening in rodents with an abrupt switch to the
      mature visual response. The switch is causally linked to the emergence of an
      activated state of continuous cortical activity dependent on the ascending
      neuromodulatory systems involved in arousal. This switch is sensory system
      specific but experience independent and also involves maturation of retinal
      processing. Thus, the early development of visual processing is governed by a
      conserved, intrinsic program that switches thalamocortical response properties in
      anticipation of patterned vision.

PMID- 20696385
TI  - Multiple timescales of memory in lateral habenula and dopamine neurons.
AB  - Midbrain dopamine neurons are thought to signal predictions about future rewards
      based on the memory of past rewarding experience. Little is known about the
      source of their reward memory and the factors that control its timescale. Here we
      recorded from dopamine neurons, as well as one of their sources of input, the
      lateral habenula, while animals predicted upcoming rewards based on the past
      reward history. We found that lateral habenula and dopamine neurons accessed two
      distinct reward memories: a short-timescale memory expressed at the start of the
      task and a near-optimal long-timescale memory expressed when a future reward
      outcome was revealed. The short- and long-timescale memories were expressed in
      different forms of reward-oriented eye movements. Our data show that the habenula
      dopamine pathway contains multiple timescales of memory and provide evidence for
      their role in motivated behavior.

PMID- 20696386
TI  - When giving is good: ventromedial prefrontal cortex activation for others'
      intentions.
AB  - In social decision-making, people care both about others' outcomes and their
      intentions to help or harm. How the brain integrates representations of others'
      intentions with their outcomes, however, is unknown. In this study, participants
      inferred others' decisions in an economic game during functional magnetic
      resonance imaging. When the game was described in terms of donations,
      ventromedial prefrontal cortex (VMPFC) activation increased for inferring
      generous play and decreased for inferring selfish play. When the game was
      described in terms of individual savings, however, VMPFC activation did not
      distinguish between strategies. Distinct medial prefrontal regions also encoded
      consistency with situational norms. A separate network, including right
      temporoparietal junction and parahippocampal gyrus, was more activated for
      inferential errors in the donation than in the savings condition. These results
      demonstrate that neural responses to others' generosity or selfishness depend not
      only on their actions but also on their perceived intentions.

PMID- 20696387
TI  - Further insights into the ubiquitin pathway: understanding the scarlet letter
      code.
AB  - Understanding the machinery that decides proteins' fate by tagging them with
      ubiquitin is an important goal of structural biology. Benirschke et al. (2010)
      have solved the structure of human E4B (or UFD2a), a U-box-containing protein
      that functions both as an E3 Ub ligase and as an E4 polyUb chain elongation
      factor.

PMID- 20696388
TI  - Articulated tubes.
AB  - High quality images of microtubules with different numbers of protofilaments, and
      hence substantially different curvatures, have been reconstructed from electron
      microscopy (EM) data (Sui and Downing, 2010). The data show how three versatile
      loops that mediate lateral interactions allow microtubules to be strong without
      being brittle.

PMID- 20696389
TI  - RIG-I "sees" the 5'-triphosphate.
AB  - RIG-I protects host cells against various RNA viruses by sensing viral RNAs in
      the cytoplasm. Crystal structures of RIG-I C-terminal domain bound to 5'
      triphosphate dsRNA unveils how RIG-I recognizes the 5'-triphosphate moiety, a
      hallmark of viral RNAs (Lu et al., 2010).

PMID- 20696390
TI  - Structures of Get3, Get4, and Get5 provide new models for TA membrane protein
      targeting.
AB  - The GET pathway, using several proteins (Gets 1-5 and probably Sgt2),
      posttranslationally conducts tail-anchored (TA) proteins to the endoplasmic
      reticulum (ER). At the ER, TA proteins are inserted into the lipid bilayer and
      then sorted and directed to their respective destinations in the secretory
      pathway. Until last year, there was no structural information on any of the GET
      components but now there are ten crystal structures of Get3 in a variety of
      nucleotide-bound states and conformations. The structures of Get4 and a portion
      of Get5 also emerged in 2010. This minireview provides a detailed comparison of
      the GET structures and discusses their mechanistic relevance to TA protein
      insertion. It also addresses the outstanding gaps in detailed molecular
      information on this system, including the structures of Get5, Sgt2, and the
      transmembrane complex comprising Get1 and Get2.

PMID- 20696391
TI  - Zernike phase contrast cryo-electron microscopy and tomography for structure
      determination at nanometer and subnanometer resolutions.
AB  - Zernike phase contrast cryo-electron microscopy (ZPC-cryoEM) is an emerging
      technique that is capable of producing higher image contrast than conventional
      cryoEM. By combining this technique with advanced image processing methods, we
      achieved subnanometer resolution for two biological specimens: 2D
      bacteriorhodopsin crystal and epsilon15 bacteriophage. For an asymmetric
      reconstruction of epsilon15 bacteriophage, ZPC-cryoEM can reduce the required
      amount of data by a factor of approximately 3, compared with conventional cryoEM.
      The reconstruction was carried out to 13 A resolution without the need to correct
      the contrast transfer function. New structural features at the portal vertex of
      the epsilon15 bacteriophage are revealed in this reconstruction. Using ZPC cryo
      electron tomography (ZPC-cryoET), a similar level of data reduction and higher
      resolution structures of epsilon15 bacteriophage can be obtained relative to
      conventional cryoET. These results show quantitatively the benefits of ZPC-cryoEM
      and ZPC-cryoET for structural determinations of macromolecular machines at
      nanometer and subnanometer resolutions.

PMID- 20696392
TI  - Structural and functional analysis of A-type ketoreductases from the amphotericin
      modular polyketide synthase.
AB  - Complex polyketides are characterized by multiple chiral centers harboring
      hydroxyl and alkyl substituents. To investigate the mechanisms by which these
      stereocenters are set, several high-resolution structures of the ketoreductase
      (KR) domain from the second module of the amphotericin modular polyketide
      synthase (PKS) were solved. This first structural analysis of an A-type KR helps
      reveal how these KRs direct polyketide intermediates into their active sites from
      the side opposite that used by B-type KRs, resulting in a beta-hydroxyl group of
      opposite stereochemistry. A comparison of structures obtained in the absence and
      presence of ligands reveals an induced fit mechanism that is important for
      catalysis. Activity assays of mutants of KRs from the first and second modules of
      the amphotericin PKS reveal the relative contributions of several active site
      residues toward catalysis and stereocontrol. Together, these results highlight
      the possibility of region-specific modification of polyketides through active
      site engineering of KRs.

PMID- 20696393
TI  - Using NMR chemical shifts as structural restraints in molecular dynamics
      simulations of proteins.
AB  - We introduce a procedure to determine the structures of proteins by incorporating
      NMR chemical shifts as structural restraints in molecular dynamics simulations.
      In this approach, the chemical shifts are expressed as differentiable functions
      of the atomic coordinates and used to compute forces to generate trajectories
      that lead to the reduction of the differences between experimental and calculated
      chemical shifts. We show that this strategy enables the folding of a set of
      proteins with representative topologies starting from partially denatured initial
      conformations without the use of additional experimental information. This method
      also enables the straightforward combination of chemical shifts with other
      standard NMR restraints, including those derived from NOE, J-coupling, and
      residual dipolar coupling measurements. We illustrate this aspect by calculating
      the structure of a transiently populated excited state conformation from chemical
      shift and residual dipolar coupling data measured by relaxation dispersion NMR
      experiments.

PMID- 20696394
TI  - Structural and functional studies of Igalphabeta and its assembly with the B cell
      antigen receptor.
AB  - The B cell antigen receptor (BCR) plays an essential role in all phases of B cell
      development. Here we show that the extracellular domains of murine and human
      Igbeta form an I-set immunoglobulin-like structure with an interchain disulfide
      between cysteines on their G strands. Structural and sequence analysis suggests
      that Igalpha displays a similar fold as Igbeta. An Igalphabeta heterodimer model
      was generated based on the unique disulfide-bonded Igbeta dimer. Solution binding
      studies showed that the extracellular domains of Igalphabeta preferentially
      recognize the constant region of BCR with mu chain specificity, suggesting a role
      for Igalphabeta to enhance BCRmu chain signaling. Cluster mutations on Igalpha,
      Igbeta, and a membrane-bound form of immunoglobulin (mIgM) based on the
      structural model identified distinct areas of potential contacts involving
      charged residues on both subunits of the coreceptor and the Cmu4 domain of mIgM.
      These studies provide the first structural model for understanding BCR function.

PMID- 20696395
TI  - Conserved beta-hairpin recognition by the GYF domains of Smy2 and GIGYF2 in mRNA
      surveillance and vesicular transport complexes.
AB  - The yeast suppressor of myosin 2 protein (Smy2) interacts with mRNA-processing
      proteins through recognition of proline-rich sequences (PRS). Here, we describe
      the crystal structure of the GYF domain of Smy2 in association with a PRS from
      the yeast branch point binding protein (BBP/ScSF1). Complex formation requires
      that the beta-hairpin of the central PPGL motif of the ligand is accommodated by
      an extended hydrophobic cleft in the domain-a specificity feature that is
      maintained in the human protein GIGYF2. SILAC/MS experiments in combination with
      PRS site inhibition show that Smy2 associates with the Ccr4-NOT deadenylase
      complex, whereas GIGYF2 interacts not only with mRNA surveillance factors, but
      also with vesicular transport proteins and Atrophin-1. GIGYF2 is shown to
      associate with COPII-vesicle proteins and localize to the ER and Golgi in resting
      cells, whereas environmental challenge drives GIGYF2 into stress granules. The
      current study highlights the structural basis for PRS recognition by Smy2-type
      GYF domains, and implicates Smy2 and GIGYF2 in both mRNA processing and the
      secretory pathway.

PMID- 20696396
TI  - Molecular basis for the association of human E4B U box ubiquitin ligase with E2
      conjugating enzymes UbcH5c and Ubc4.
AB  - Human E4B, also called UFD2a, is a U box-containing protein that functions as an
      E3 ubiquitin ligase and an E4 polyubiquitin chain elongation factor. E4B is
      thought to participate in the proteasomal degradation of misfolded or damaged
      proteins through association with chaperones. The U box domain is an anchor site
      for E2 ubiquitin-conjugating enzymes, but little is known of the binding
      mechanism. Using X-ray crystallography and NMR spectroscopy, we determined the
      structures of E4B U box free and bound to UbcH5c and Ubc4 E2s. Whereas previously
      characterized U box domains are homodimeric, we show that E4B U box is a monomer
      stabilized by a network of hydrogen bonds identified from scalar coupling
      measurements. These structural studies, complemented by calorimetry- and NMR
      based binding assays, suggest an allosteric regulation of UbcH5c and Ubc4 by E4B
      U box and provide a molecular basis to understand how the ubiquitylation
      machinery involving E4B assembles.

PMID- 20696397
TI  - Polycomb group targeting through different binding partners of RING1B C-terminal
      domain.
AB  - RING1B, a Polycomb Group (PcG) protein, binds methylated chromatin through its
      association with another PcG protein called Polycomb (Pc). However, RING1B can
      associate with nonmethylated chromatin suggesting an alternate mechanism for
      RING1B interaction with chromatin. Here, we demonstrate that two proteins with
      little sequence identity between them, the Pc cbox domain and RYBP, bind the same
      surface on the C-terminal domain of RING1B (C-RING1B). Pc cbox and RYBP each fold
      into a nearly identical, intermolecular beta sheet with C-RING1B and a loop
      structure which are completely different in the two proteins. Both the beta sheet
      and loop are required for stable binding and transcription repression. Further, a
      mutation engineered to disrupt binding on the Drosophila dRING1 protein prevents
      chromatin association and PcG function in vivo. These results suggest that PcG
      targeting to different chromatin locations relies, in part, on binding partners
      of C-RING1B that are diverse in sequence and structure.

PMID- 20696398
TI  - Structural role of the Vps4-Vta1 interface in ESCRT-III recycling.
AB  - The ESCRT complexes are required for multivesicular body biogenesis,
      macroautophagy, cytokinesis, and the budding of HIV-1. The final step in the
      ESCRT cycle is the disassembly of the ESCRT-III lattice by the AAA+ ATPase Vps4.
      Vps4 assembles on its membrane-bound ESCRT-III substrate with its cofactor, Vta1.
      The crystal structure of the dimeric VSL domain of yeast Vta1 with the small
      ATPase and the betadomains of Vps4 was determined. Residues involved in
      structural interactions are conserved and are required for binding in vitro and
      for Cps1 sorting in vivo. Modeling of the Vta1 complex in complex with the lower
      hexameric ring of Vps4 indicates that the two-fold axis of the Vta1 VSL domain is
      parallel to within approximately 20 degrees of the six-fold axis of the hexamer.
      This suggests that Vta1 might not crosslink the two hexameric rings of Vps4, but
      rather stabilizes an array of Vps4-Vta1 complexes for ESCRT-III disassembly.

PMID- 20696399
TI  - The RalB-RLIP76 complex reveals a novel mode of ral-effector interaction.
AB  - RLIP76 (RalBP1) is a multidomain protein that interacts with multiple small G
      protein families: Ral via a specific binding domain, and Rho and R-Ras via a
      GTPase activating domain. RLIP76 interacts with endocytosis proteins and has also
      been shown to behave as a membrane ATPase that transports chemotherapeutic agents
      from the cell. We have determined the structure of the Ral-binding domain of
      RLIP76 and show that it comprises a coiled-coil motif. The structure of the
      RLIP76-RalB complex reveals a novel mode of binding compared to the structures of
      RalA complexed with the exocyst components Sec5 and Exo84. RLIP76 interacts with
      both nucleotide-sensitive regions of RalB, and key residues in the interface have
      been identified using affinity measurements of RalB mutants. Sec5, Exo84, and
      RLIP76 bind Ral proteins competitively and with similar affinities in vitro.

PMID- 20696400
TI  - Crystal structures of Phd-Doc, HigA, and YeeU establish multiple evolutionary
      links between microbial growth-regulating toxin-antitoxin systems.
AB  - Bacterial toxin-antitoxin (TA) systems serve a variety of physiological functions
      including regulation of cell growth and maintenance of foreign genetic elements.
      Sequence analyses suggest that TA families are linked by complex evolutionary
      relationships reflecting likely swapping of functional domains between different
      TA families. Our crystal structures of Phd-Doc from bacteriophage P1, the HigA
      antitoxin from Escherichia coli CFT073, and YeeU of the YeeUWV systems from E.
      coli K12 and Shigella flexneri confirm this inference and reveal additional,
      unanticipated structural relationships. The growth-regulating Doc toxin exhibits
      structural similarity to secreted virulence factors that are toxic for eukaryotic
      target cells. The Phd antitoxin possesses the same fold as both the YefM and
      NE2111 antitoxins that inhibit structurally unrelated toxins. YeeU, which has an
      antitoxin-like activity that represses toxin expression, is structurally similar
      to the ribosome-interacting toxins YoeB and RelE. These observations suggest
      extensive functional exchanges have occurred between TA systems during bacterial
      evolution.

PMID- 20696401
TI  - Mapping the interactions between a major pollen allergen and human IgE
      antibodies.
AB  - The interaction of specific IgE antibodies with allergens is a key event in the
      induction of allergic symptoms, thus representing an important target for
      therapeutic interventions in Type I allergies. We report here the solution NMR
      structure of Art v 1, the major mugwort pollen allergen. Art v 1 is the first
      protein structure with an allergenic defensin fold linked to a polyproline
      domain, which has not been identified in any reported allergen structure in the
      PDB. Moreover, the direct interaction of polyclonal IgE antibodies from an
      allergic patient has been mapped on the surface of an allergen for the first
      time. The data presented herein provide the basis for the design of tools for
      safe and effective vaccination against mugwort pollen allergy.

PMID- 20696402
TI  - Structural basis of interprotofilament interaction and lateral deformation of
      microtubules.
AB  - The diverse functions of microtubules require stiff structures possessing
      sufficient lateral flexibility to enable bending with high curvature. We used
      cryo-electron microscopy to investigate the molecular basis for these critical
      mechanical properties. High-quality structural maps were used to build
      pseudoatomic models of microtubules containing 11-16 protofilaments, representing
      a wide range of lateral curvature. Protofilaments in all these microtubules were
      connected primarily via interprotofilament interactions between the M loops, and
      the H1'-S2 and H2-S3 loops. We postulate that the tolerance of the loop-loop
      interactions to lateral deformation provides the capacity for high-curvature
      bending without breaking. On the other hand, the local molecular architecture
      that surrounds these connecting loops contributes to the overall rigidity.
      Interprotofilament interactions in the seam region are similar to those in the
      normal helical regions, suggesting that the existence of the seam does not
      significantly affect the mechanical properties of microtubules.

PMID- 20696404
TI  - Structure and function of sphingosine-1-phosphate lyase, a key enzyme of
      sphingolipid metabolism.
AB  - Sphingosine-1-phosphate lyase (SPL), a key enzyme of sphingolipid metabolism,
      catalyzes the irreversible degradation of sphingoid base phosphates. Its main
      substrate sphingosine-1-phosphate (S1P) acts both extracellularly, by binding G
      protein-coupled receptors of the lysophospholipid receptor family, and inside the
      cell, as a second messenger. There, S1P takes part in regulating various cellular
      processes and its levels are tightly regulated. SPL is a pivotal enzyme
      regulating S1P intracellular concentrations and a promising drug target for the
      design of immunosuppressants. We structurally and functionally characterized
      yeast SPL (Dpl1p) and its first prokaryotic homolog, from Symbiobacterium
      thermophilum. The Dpl1p structure served as a basis for a very reliable model of
      Homo sapiens SPL. The above results, together with in vitro and in vivo studies
      of SPL mutants, reveal which residues are involved in activity and substrate
      binding and pave the way to studies aimed at controlling the activity of this
      pivotal enzyme.

PMID- 20696405
TI  - A tribute to Professor Jeremiah Morris: the man who invented the field of
      physical activity epidemiology.

PMID- 20696403
TI  - The macromolecular architecture of extracellular domain of alphaNRXN1: domain
      organization, flexibility, and insights into trans-synaptic disposition.
AB  - Neurexins are multidomain synaptic cell-adhesion proteins that associate with
      multiple partnering proteins. Genetic evidence indicates that neurexins may
      contribute to autism, schizophrenia, and nicotine dependence. Using analytical
      ultracentrifugation, single-particle electron microscopy, and solution X-ray
      scattering, we obtained a three-dimensional structural model of the entire
      extracellular domain of neurexin-1alpha. This protein adopts a dimensionally
      asymmetric conformation that is monomeric in solution, with a maximum dimension
      of approximately 170 A. The extracellular domain of alpha-neurexin maintains a
      characteristic "Y" shape, whereby LNS domains 1-4 form an extended base of the
      "Y" and LNS5-6 the shorter arms. Moreover, two major regions of flexibility are
      present: one between EGF1 and LNS2, corresponding to splice site 1, another
      between LNS5 and 6. We thus provide the first structural insights into the
      architecture of the extracellular region of neurexin-1alpha, show how the protein
      may fit in the synaptic cleft, and how partnering proteins could bind
      simultaneously.

PMID- 20696406
TI  - Relationship among alcohol intake, body fat, and physical activity: a population
      based study.
AB  - OBJECTIVES: Aside from fat, ethanol is the macronutrient with the greatest energy
      density. Whether the energy derived from ethanol affects body composition and fat
      mass is debatable. We investigated the relationship of alcohol intake, body
      composition, and physical activity in the U.S. population by using data from the
      Third National Health and Nutrition Examination Survey (NHANES III). METHODS: A
      total of 10,550 subjects met eligibility criteria and constituted our study
      cohort. Estimated percent body fat and resting metabolic rate were calculated on
      the basis of the sum of the skinfolds. Multivariate regression analyses were
      performed accounting for the study sampling weight. RESULTS: In both sexes,
      moderate and hazardous alcohol drinkers were younger (p < .05) and had
      significantly lower body mass index (p < 0.01) and body weight (p < 0.01) than
      non-drinkers. Those with hazardous alcohol consumption participated in
      significantly less physical activity compared with those with no alcohol use and
      moderate drinkers in both sexes. Women had significantly greater percent body fat
      than men. In multivariate linear regression analyses, the levels of alcohol
      consumption were found to be an independent predictor associated with lower
      percent body fat only in male subjects. CONCLUSIONS: Our results showed that
      alcoholics are habitually less active and that alcohol drinking is an independent
      predictor of lower percent body fat, especially in male alcoholics.

PMID- 20696407
TI  - Role of lifetime body mass index in the association between age at puberty and
      adult lipids: findings from men and women in a British birth cohort.
AB  - PURPOSE: Why early puberty is associated with worse cardiovascular outcomes is
      unknown. The relationship between puberty and lipids is unclear. Our aim was to
      assess whether age at puberty was associated with triglyceride and total low
      density lipoprotein and high-density lipoprotein cholesterol at age 53 years.
      METHODS: Participants in a national birth cohort were examined at 15 years, when
      pubertal stage for boys was assessed and age at menarche reported by the girls'
      mothers. At 53 years, 3035 were interviewed in their homes by research nurses,
      where blood was taken. RESULTS: There was a significant inverse relationship in
      women but not men between age at puberty (in years) and triglycerides (regression
      coefficient -0.2.9, 95% confidence interval -5.5, to -0.04, p = .02), age at
      puberty, and age at puberty and adult body mass index (BMI; p < .001).
      Relationships between puberty and lipids were completely explained by BMI or
      waist circumference at 53 years. CONCLUSIONS: In both sexes earlier maturation
      was associated with greater BMI and waist circumference in later life, which
      resulted in greater triglycerides and cholesterol in women. We suggest that
      intervention after puberty to help avoid obesity in early maturing women may
      improve their later cardiovascular health.

PMID- 20696408
TI  - Paired comparison of observed and expected coronary heart disease rates over 12
      years from the Atherosclerosis Risk in Communities Study.
AB  - PURPOSE: To quantify the relationship between coronary heart disease (CHD) risk
      factor levels and changes over time and population-wide CHD morbidity and
      mortality. METHODS: We used a paired cohort and community surveillance of
      hospitalized myocardial infarction and CHD deaths of community members 53 to 64
      years of age in four geographic areas to compare observed community CHD to
      expected CHD rates and trends based on cohort risk factors. RESULTS: Observed CHD
      rates declined by 1% to 3% per year in all communities except one, whereas CHD
      death rates declined 3% to 6% per year in all communities. Risk factor trends
      predicted a 2% to 3% per year decline in both total events and death. In all
      communities except one, expected rates of total CHD events were lower than the
      observed rates, whereas expected and observed CHD death rates were similar.
      Across all communities women had a higher CHD death rate than expected.
      CONCLUSION: Overall, trends in CHD risk factors provide a useful indicator of
      changes in community event rates and of CHD death, but caution is warranted in
      prediction of absolute risk of CHD events.

PMID- 20696409
TI  - What does a good outcome really mean and who determines it?

PMID- 20696411
TI  - An impact factor for JMBBM.

PMID- 20696412
TI  - Effect of microwave disinfection on mechanical properties of denture base acrylic
      resin.
AB  - The microwave oven was used for sterilizing dentures contaminated with Candida
      albicans and other communicable diseases instead of disinfectant solutions. This
      study was carried out to evaluate the flexural properties, toughness, and impact
      strength of heat-cured acrylic resin sterilized by microwave oven either immersed
      in water or non-immersed for 5 and 15 min at full power. The results indicated
      that the microwave oven sterilization technique resulted in reduction of the load
      necessary to fracture the specimens, deformation at fracture, transverse
      strength, modulus of elasticity except disinfection at 5 min dry condition,
      toughness, and impact strength. This study concluded that the microwave oven is
      not acceptable for sterilization of dentures because of its weakening effects on
      the dentures that prone for fracture during clinical use. This method of
      sterilization increased the brittleness of acrylic resin specimens.

PMID- 20696410
TI  - Learning from Jekyll to control Hyde: Hedgehog signaling in development and
      cancer.
AB  - The Hedgehog (Hh) cascade controls cell proliferation, differentiation and
      patterning of tissues during embryogenesis but is largely suppressed in the
      adult. The Hh pathway can become reactivated in cancer. Here, we assimilate data
      from recent studies to understand how and when the Hh pathway is turned on to aid
      the neoplastic process. Hh signaling is now known to have a role in established
      tumors, enabling categorization of tumors based on the role Hh signaling plays in
      their growth. This categorization has relevance for prognosis and targeted
      therapeutics. In the first category, abnormal Hh signaling initiates the tumor.
      In the second category, Hh signaling helps maintain the tumor. In the third
      category, Hh signaling is implicated but its role is not yet defined.

PMID- 20696413
TI  - Surface integrity and process mechanics of laser shock peening of novel
      biodegradable magnesium-calcium (Mg-Ca) alloy.
AB  - Current permanent metallic biomaterials of orthopedic implants, such as titanium,
      stainless steel, and cobalt-chromium alloys, have excellent corrosive properties
      and superior strengths. However, their strengths are often too high resulting in
      a stress shielding effect that is detrimental to the bone healing process.
      Without proper healing, costly and painful revision surgeries may be required.
      The close Young's modulus between magnesium-based implants and cancellous bones
      has the potential to minimize stress shielding while providing both
      biocompatibility and adequate mechanical properties. The problem with Mg implants
      is how to control corrosion rates so that the degradation of Mg implants matches
      that of bone growth. Laser shock peening (LSP) is an innovative surface treatment
      method to impart compressive residual stress to a novel Mg-Ca implant. The high
      compressive residual stress has great potential to slow corrosion rates.
      Therefore, LSP was initiated in this study to investigate surface topography and
      integrity produced by sequential peening a Mg-Ca alloy. Also, a 3D semi-infinite
      simulation was developed to predict the topography and residual stress fields
      produced by sequential peening. The dynamic mechanical behavior of the
      biomaterial was modeled using a user material subroutine from the internal state
      variable plasticity model. The temporal and spatial peening pressure was modeled
      using a user load subroutine. The simulated dent agrees with the measured dent
      topography in terms of profile and depth. Sequential peening was found to
      increase the tensile pile-up region which is critical to orthopedic applications.
      The predicted residual stress profiles are also presented.

PMID- 20696414
TI  - Elastic characteristics of microspherical embolic agents used for vascular
      interventional radiology.
AB  - Embolic agents are used in vascular interventional radiology to occlude arteries
      under pathological conditions. The present study was performed to investigate the
      material properties of two microspherical embolic agents (MSEAs), tris-acryl
      gelatin microspheres (TGMS) and superabsorbent polymer microsphere (SAP-MS),
      using a loading-unloading compression test. The results demonstrated that for
      both TGMS and SAP-MS, the stress-strain relationship appeared to be linear up to
      25% deformation. Therefore, one can reasonably treat TGMS and SAP-MS as linearly
      elastic materials for this range of deformation and apply the Hertz contact
      theory for analysis of the Young's modulus. The Young's moduli of TGMS and the
      SAP-MS obtained by applying Hertz theory under the assumption of a Poisson's
      ratio of 0.5 were 19.33 +/- 4.97 kPa and 9.64 +/- 2.46 kPa, respectively (mean +/
      SD, P<0.001, Mann-Whitney U-test), indicating that TGMS showed higher stiffness
      than SAP-MS. The effects of a difference in these mechanical characteristics of
      embolic agents on the performance of interventional radiology were discussed from
      a viewpoint of their flowing behavior and clinical aspects.

PMID- 20696415
TI  - Improved fatigue life of acrylic bone cements reinforced with zirconia fibers.
AB  - Poly(methyl methacrylate) (PMMA) bone cements have a long and successful history
      of use for implant fixation, but suffer from a relatively low fracture and
      fatigue resistance which can result in failure of the cement and the implant.
      Fiber or particulate reinforcement has been used to improve mechanical
      properties, but typically at the expense of the pre-cured cement viscosity, which
      is critical for successful integration with peri-implant bone tissue. Therefore,
      the objective of this study was to investigate the effects of zirconia fiber
      reinforcement on the fatigue life of acrylic bone cements while maintaining a
      relatively low pre-cured cement viscosity. Sintered straight or variable diameter
      fibers (VDFs) were added to a PMMA cement and tested in fully reversed uniaxial
      fatigue until failure. The mean fatigue life of cements reinforced with 15 and 20
      vol% straight zirconia fibers was significantly increased by approximately 40
      fold, on average, compared to a commercial benchmark (Osteobond) and cements
      reinforced with 0-10 vol% straight zirconia fibers. The mean fatigue life of a
      cement reinforced with 10 vol% VDFs was an order of magnitude greater than the
      same cement reinforced with 10 vol% straight fibers. The time-dependent viscosity
      of cements reinforced with 10 and 15 vol% straight fibers was comparable to the
      commercial benchmark during curing. Therefore, the addition of relatively small
      amounts of straight and variable diameter zirconia fibers was able to
      substantially improve the fatigue resistance of acrylic bone cement while
      exhibiting similar handling characteristics compared to current commercial
      products.

PMID- 20696416
TI  - A biomechanical study on burst mechanisms of plant fruit: stress analysis of
      pericarps before bursting.
AB  - Bursting of fruit is a very interesting biomechanical phenomenon because its
      mechanism is directly related to the plant's reproduction. A plant that produces
      fruit that bursts powerfully and spreads the seeds widely has the advantage of
      reproduction without relying on other mechanisms such as transportation of fruit
      by insects. The structures of many types of fruit have likely been optimized by
      evolution, although the structure itself appears rather simplistic. Strain energy
      is stored in each pericarp because of growth deformation, swelling or desiccation
      just before bursting. Throughout these changes, the mechanical stress of the
      pericarps is at equilibrium. At the instant of bursting, the stored strain energy
      is released very rapidly. Quick and wide motion of the pericarps in a certain
      direction is advantageous for throwing the seed a long distance. The motion and
      deformation of bursting pericarps depend on their tissue structure and mechanical
      stress condition just before the burst. We tracked the bursting motion by using a
      high-speed camera. Then we calculated the pre-burst stress generated in a
      pericarp of Impatiens by using the finite-element method. The boundary condition
      obtained by experiments using a high-speed video camera is given, and the stress
      was calculated using reverse deformation analysis. The stress distribution of the
      pericarp is effective in causing the pericarp motion to throw the seeds far away.

PMID- 20696417
TI  - In vitro evaluation of mechanical characteristics of a novel Patent Ductus
      Arteriosus (PDA) occlusion device with a new lateral pressure measurement study.
AB  - Persistence of the ductus arteriosus (DA), connecting the aorta to the pulmonary
      artery, after birth leads to a congenital heart disease known as Patent Ductus
      Arteriosus (PDA). The objective of this study was to propose a new intraductal
      design for PDA occlusion and determine the efficacy of the new device by means of
      an in vitro mechanical evaluation. A novel intraductal design device called the
      Novel design 36 (ND36) was proposed, fabricated and tested. Mechanical tests
      included tests to determine the mechanical characteristics, force-displacement
      characteristics, stiffness, device slenderization, minimum diameter attained,
      insertion force required to pull device at site and lateral pressure exerted on
      the PDA walls. Comparative analysis was carried out with the Amplatzer Duct
      Occluder (AGA Medical Corporation, Golden Valley, MN). The results showed that
      the ND36 when fully stretched was shorter than the ADO implying an easier in vivo
      movement. The minimum diameter attained by ND36 is 2.52 mm which is compatible
      with standard catheter bores of 6-8 Fr (2-2.7 mm) bore sizes. A new setup was
      devised in order to carry out comparative lateral pressure measurements between
      the ND36 and ADO. The results showed that the ND36 exerted a pressure of 10 KPa
      (=75 mm Hg) and the ADO exerted 80 KPa (=600 mm Hg) over the walls of the tubes
      which is a physiologically promising result for the ND36 as it shows that the
      ND36 would exert lesser stress on the walls of the duct. The results suggest that
      the novel intraductal design (ND36) would prove to be a safer, reliable and
      effective device for PDA occlusion.

PMID- 20696418
TI  - Improvement of mechanical properties and biocompatibility of forsterite
      bioceramic addressed to bone tissue engineering materials.
AB  - This work deals with the fabrication and characterization of nanostructured
      forsterite bulk. This material may have better biocompatibility and mechanical
      properties than coarse grain forsterite for the development of bone tissue
      engineering materials. Nanostructured forsterite bulks were prepared by two step
      sintering of sol-gel derived forsterite nanopowder. Their sinterability and
      mechanical properties were then studied. Biocompatibility of the nanostructured
      forsterite bulk was also evaluated by cell attachment and proliferation
      experiments. In addition, the effects of ionic products from forsterite
      nanopowder dissolution on osteoblasts were studied. Results show that dense
      nanostructured forsterite bulk was prepared with hardness and fracture toughness
      of about 1102 Hv and 4.3 MPa m(1/2), respectively. Nanostructured forsterite was
      biocompatible and the MTT test confirmed that the products from forsterite
      nanopowder dissolution significantly promoted osteoblast proliferation within a
      certain concentration range. In addition, cells attached to and spread on the
      surface of nanostructured forsterite bulks. Mechanical properties of the
      nanostructured forsterite were much higher than that of hydroxyapatite. It was
      concluded that nanostructured forsterite is a bioactive ceramic with good
      biocompatibility that can be used as a bone tissue engineering material.

PMID- 20696419
TI  - A model for the stretch-mediated enzymatic degradation of silk fibers.
AB  - To restore physiological function through regenerative medicine, biomaterials
      introduced into the body must degrade at a rate that matches new tissue
      formation. For effective therapies, it is essential that we understand the
      interaction between physiological factors, such as routine mechanical loading
      specific to sites of implantation, and the resultant rate of material
      degradation. These relationships are poorly characterized at this time. We
      hypothesize that mechanical forces alter the rates of remodeling of biomaterials,
      and this impact is modulated by the concentration of enzymes and the duration of
      the mechanical loads encountered in situ. To test this hypothesis we subjected
      silk fibroin fibers to repeated cyclic loading in the presence of enzymatic
      degradation (either alpha-chymotrypsin or Protease XIV) and recorded the stress
      strain response. Data were collected daily for a duration of 2 weeks and compared
      to the control cases of stretched fibers in the presence of phosphate buffered
      saline or non-stretched samples in the presence of enzyme alone. We observed that
      incubation with proteases in the absence of mechanical loads causes a reduction
      of the ultimate tensile strength but no change in stiffness. However, cyclic
      loading caused the accumulation of residual strain and softening in the
      material's properties. We utilize these data to formulate a mathematical model to
      account for residual strain and reduction of mechanical properties during silk
      fiber degradation. Numerical predictions are in fair agreement with experimental
      data. The improved understanding of the degradation phenomenon will be
      significant in many clinical repair cases and may be synergistic to decrease
      silk's mechanical properties after in vivo implantation.

PMID- 20696420
TI  - Flexible work in call centres: Working hours, work-life conflict & health.
AB  - Call-centre workers encounter major psychosocial pressures, including high work
      intensity and undesirable working hours. Little is known, however, about whether
      these pressures vary with employment status and how they affect work-life
      conflict and health. Questionnaire data were collected from 179 telephone
      operators in Sydney, Australia, of whom 124 (69.3%) were female and 54 (30.2%)
      were male. Ninety-three (52%) were permanent full-time workers, 37 (20.7%) were
      permanent part-time, and 49 (27.4%) were casual employees. Hypothesised
      structural relationships between employment status, working hours and work
      organisation, work-life conflict and health were tested using partial least
      squares modelling in PLS (Chin, 1998). The final model demonstrated satisfactory
      fit. It supported important elements of the hypothesised structure, although four
      of the proposed paths failed to reach significance and the fit was enhanced by
      adding a path. The final model indicated that casual workers reported more
      variable working hours which were relatively weakly associated with greater
      dissatisfaction with hours. The interaction of schedule control and variability
      of hours also predicted dissatisfaction with hours. Conversely, permanent workers
      reported greater work intensity, which was associated with both lower work
      schedule control and greater work-life conflict. Greater work-life conflict was
      associated with more fatigue and psychological symptoms. Labour market factors
      and the undesirability of longer hours in a stressful, high-intensity work
      environment appear to have contributed to the results.

PMID- 20696421
TI  - Effectiveness of group cognitive-behavioral treatment for childhood anxiety in
      community clinics.
AB  - This study evaluated the effectiveness of cognitive-behavioral treatment for
      childhood anxiety in a community clinic setting in Hong Kong, China. Forty-five
      clinically-referred children (age 6-11 years) were randomly assigned to either a
      cognitive-behavioral treatment program or a waitlist-control condition. Children
      in the treatment condition showed significant reduction in anxiety symptoms-both
      statistically and clinically-whereas children in the waitlist condition did not.
      After the waitlist period was over, the control group also received the treatment
      program and showed a similar reduction in symptoms. For the full sample of 45
      children, the effectiveness of the intervention was significant immediately after
      treatment and in 3- and 6-month follow-ups. In addition, children's anxiety
      cognition and their ability to cope with anxiety-provoking situations fully
      mediated the treatment gains. These results offer empirical support for cognitive
      behavioral treatment programs in a non-Western cultural context and plausible
      mediators for how cognitive-behavioral therapy works.

PMID- 20696422
TI  - Altered signaling through IL-12 receptor in children with very high serum IgE
      levels.
AB  - An alteration of Th1/Th2 homeostasis may lead to diseases in humans. In this
      study, we investigated whether an impaired IL-12R signaling occurred in children
      with elevated serum IgE levels divided on the basis of the IgE levels (group A:
      >2000kU/l; group B: <2000kU/l). We evaluated the integrity of the IL-12R
      signaling through the analysis of phosphorylation/activation of STAT4, and mRNA
      expression and membrane assembly of the receptor chains. At a functional level, a
      proliferative defect of lymphocytes from group A patients was observed. In these
      patients, an abnormal IL-12R signaling was documented, and this finding was
      associated with abnormal expression of the IL-12Rbeta2 chain. Our data indicate
      that in patients with very high IgE levels the generation of Th1 response is
      impaired, and that this abnormality associates with abnormal IL-12R signaling.

PMID- 20696424
TI  - Observing fearful faces leads to visuo-spatial perspective taking.
AB  - A number of recent studies suggested that visuo-spatial perspective taking (VSPT)
      occurs spontaneously when viewing either a human body or an action by an agent.
      However, it remains unclear whether VSPT is caused by the observation of an
      (potential) action or occurs because the observer infers from certain cues that
      another mind is present (whether actions/action cues are displayed or not). To
      examine whether action cues are necessary for VSPT, we presented to participants
      human faces without a torso, that is: stimuli that indicated the presence of
      another mind, without providing action (effector) cues. Furthermore, we examined
      whether 'relevance' of understanding the other mind would influence VSPT, where
      relevance was manipulated by comparing the effects of observing a fearful versus
      a neutral facial expression on VSPT. Results showed that spontaneous VSPT occurs
      when a face with a fearful, but not with a neutral, expression is perceived. This
      indicates that spontaneous VSPT occurs (at least more robustly) under
      circumstances, where VSPT is of 'relevance' for understanding the situation.
      Furthermore, directly observing actions, or action cues, does not appear to be a
      prerequisite for VSPT.

PMID- 20696425
TI  - Effects of perfluorooctanesulfonate exposure on plasma lipid levels in the Inuit
      population of Nunavik (Northern Quebec).
AB  - BACKGROUND: Perfluorooctanesulfonate (PFOS) was used as a surfactant in various
      commercial products. In rodents, exposure to this compound induced various health
      effects, including hypolipidemia. In human populations, the potential toxicity of
      PFOS is not yet fully characterized, but indications of effects on lipids are
      reported. A recent study reported an increase in plasma cholesterol associated
      with exposure to perfluorinated compounds in humans exposed through drinking
      water, but similar effects were not reported in all exposed human populations.
      PFOS is widely distributed in the environment, including the arctic biota. The
      Inuit of Nunavik are exposed to environmental contaminants through the
      consumption of fish and game. This diet is also a source of omega3
      polyunsaturated fatty acids (n-3 PUFAs) that are known to lower plasma
      triacylglycerols. OBJECTIVE: This cross-sectional epidemiologic study aims at
      assessing the relationship between PFOS exposure and plasma lipids, while taking
      account of the concomitant hypolipidemic effect exerted by n-3 PUFAs. METHODS:
      Plasma concentrations of PFOS and lipids were assessed in Nunavik Inuit adults
      (n=723) in the framework of a large-scale environmental health study.
      Associations of exposure levels to age, gender and selected wild food consumption
      associated with n-3 PUFAs intake, as well as the exposure on lipid levels were
      investigated by multivariate linear modeling. RESULTS: In the Inuit population,
      PFOS exposure and n-3 PUFAs intake are related to traditional food consumption.
      Triacylglycerol and ratio of total cholesterol to high density lipoprotein
      cholesterol (HDL-C) levels were negatively associated with PFOS plasma levels,
      while HDL-C levels were positively associated, after adjustment for circulating
      levels of n-3 PUFAs and for the interaction between gender and PFOS plasma
      levels. Other plasma lipids, such as low density lipoprotein-cholesterol and non
      HDL-C were not related to PFOS plasma concentrations. CONCLUSION: The results of
      this study show a relationship between PFOS and plasma lipid levels in an
      environmentally exposed human population, and this effect appears distinct from
      that of n-3 PUFAs.

PMID- 20696426
TI  - Minimal invasive long PHILOS(r)-plate osteosynthesis in metadiaphyseal fractures
      of the proximal humerus.
AB  - Minimal invasive plate osteosynthesis (MIPO) not only meets the criteria of a
      "biological" osteosynthesis by minimising invasivity as well as iatrogenic soft
      tissue damage, but can also provide adequate stability for fracture healing and
      early functional aftertreatment. Up to date, only few publications report on MIPO
      of humeral shaft fractures mainly using the anterolateral deltopectoral approach
      for proximal plate insertion. Objective of the present study was to assess the
      feasibility and clinical outcome of MIPO for metadiaphyseal fractures of the
      proximal humerus through a lateral approach using angular stable long PHILOS((r))
      plates. We retrospectively evaluated 29 patients (mean age 77 years, range 48-95
      years) with displaced metadiaphyseal fractures of the proximal humerus treated
      with MIPO technique. For the first time, an angular stable long PHILOS((r))-plate
      through a lateral deltoid-split approach proximally and a
      brachialis/brachioradialis intermuscular approach with exposure of the radial
      nerve distally, were used. There were no infections and no iatrogenic injuries to
      the axillary and radial nerve. One patient showed subacromial impingement and one
      patient had to be reoperated for redislocation of the distal fragment with screw
      breakage, which was most likely due to incorrect screw placement. This patient
      was successfully operated using the same method and implant. Besides one patient
      who refused further follow-up, 28 patients could be followed up to a mean of 8
      months (range 3-12 months) each with an entirely healed fracture. Furthermore,
      patient's quality of life was documented using the SF-36 questionnaire.
      Comparison with published United States normative data showed no significant
      deficits in the physical as well as in the mental domains 8 months after MIPO.
      Minimal invasive long PHILOS((r))-plate osteosynthesis using a combined lateral
      deltoid-split and brachialis/brachioradialis intermuscular approach proved to be
      a safe procedure for the treatment of metadiaphyseal fractures of the proximal
      humerus with low morbidity and full restoration of quality of life in these
      elderly patients.

PMID- 20696427
TI  - Early-career burnout among new graduate nurses: a prospective observational study
      of intra-individual change trajectories.
AB  - BACKGROUND: Newly qualified and inexperienced nurses are at particular risk of
      suffering emotional exhaustion and burnout in unsupportive practice environments.
      Despite new nurses' potential vulnerability, development of burnout after
      graduation has rarely been studied longitudinally and in relation to demographic
      and educational characteristics prior to working life entry, i.e. during
      education. OBJECTIVES: To identify and compare typical change trajectories (i.e.
      common patterns of intra-individual development) in burnout symptoms for new
      graduate nurses annually over a three-year period, during which there was reason
      to believe that this group was especially vulnerable. DESIGN: A prospective
      longitudinal and national cohort of 1153 nurses within the population-based LANE
      study (Longitudinal Analyses of Nursing Education), where new graduate nurses
      were assessed four times annually, i.e. in their final year of nursing education
      and three times post graduation (after 1, 2 and 3 years). PARTICIPANTS: A
      longitudinal sample of 997 respondents was prospectively followed. METHODS:
      Within-group changes in burnout levels were analysed using a repeated-measures
      analysis of variance, and cluster analytic techniques were used to identify
      typical trajectories of burnout. RESULTS: At group level, mean levels of burnout
      were rather stable across time. However, underlying these levels we identified
      eight change trajectories, explaining 74% of all individual variation; seven of
      them reflected significant changes across time. Almost every fifth nurse reported
      extremely high levels of burnout at some point during their first three years
      after graduation. Changes in burnout levels were accompanied by concurrent
      changes in depressive symptoms and intention to leave the profession. This study
      also showed that negative development of burnout was predicted by not feeling
      well prepared for a nursing job, lacking study interest, high levels of
      performance-based self-esteem and depressive mood in the final year of education.
      CONCLUSIONS: An investigation of burnout symptoms over time disclosed numerous
      development patterns, some of which were stable while others changed
      significantly. Hence, this study gave a more nuanced picture of burnout
      development among new graduate nurses, highlighted by eight different
      trajectories. Regarding the time frame, nearly every second new graduate showed a
      significant increase in levels of burnout during their second year post
      graduation.

PMID- 20696428
TI  - Sleep-related predictors of quality of life in the elderly versus younger heart
      failure patients: a questionnaire survey.
AB  - BACKGROUND: Research has indicated that sleep disorders reduce the quality of
      life of heart failure patients. OBJECTIVES: To investigate quality of sleep, and
      the impact of poor sleep on quality of life among elderly versus younger heart
      failure patients. DESIGN: A two-group, cross-sectional study. SETTING: A
      community teaching hospital in Taipei, Taiwan. PARTICIPANTS: Voluntarily self
      enrolled heart failure patients who did not have sleep apnea or restless leg
      syndrome. METHODS: There were 126 elderly and 67 young participants filled out
      five questionnaires (1) demographic information and current health status; (2)
      the Chinese Pittsburgh Sleep Quality Index; (3) the Chinese Epworth Sleepiness
      Scale, and (4) the short form (SF)-36 Taiwanese version. The major statistical
      procedures applied in this study were t-test, analysis of variance, Pearson's
      correlation, and a stepwise multiple linear regression. A p-value of <0.05 was
      adopted as significant. RESULTS: The prevalence of insomnia was 44.4% for the
      elderly group and 31.4% for the younger group. The top three prevalence sleep
      disturbing events were: nocturia, long sleep latency, and early wake-up. In the
      elderly group, nocturnal dyspnea and long sleep latency were significant
      determinants of the mental (R(2)=0.23) and physical components (R(2)=0.21) of
      quality of life. In the young group, nocturnal dyspnea was a significant
      determinant of the mental component of quality of life (R(2)=0.15), and early
      wake-up was a significant determinant of the physical component of quality of
      life (R(2)=0.15). CONCLUSION: The sleep disorder of heart failure patients is
      disease-specific rather than a matter of age. The prevalence of insomnia of young
      heart failure patients was higher than that of the healthy elderly. The major
      determinants of poor night sleep quality in the elderly group were dyspnea and
      long sleep latency, and in the younger group, these were dyspnea and early wake
      up. Those also were significant determinants of quality of life of the heart
      failure patients. IMPLICATIONS FOR NURSING PRACTICE: Since the sleep-related
      predictors of quality of life were different in the elderly versus younger heart
      failure patients, to identify the insomnia factors individually and to provide
      guidance of appropriate usage of sleep medications and other methods to promote
      sleep should be considered.

PMID- 20696429
TI  - The impact of the nursing hours per patient day (NHPPD) staffing method on
      patient outcomes: a retrospective analysis of patient and staffing data.
AB  - BACKGROUND: In March 2002 the Australian Industrial Relations Commission ordered
      the introduction of a new staffing method - nursing hours per patient day (NHPPD)
      - for implementation in Western Australia public hospitals. This method used a
      "bottom up" approach to classify each hospital ward into one of seven categories
      using characteristics such as patient complexity, intervention levels, the
      presence of high dependency beds, the emergency/elective patient mix and patient
      turnover. Once classified, NHPPD were allocated for each ward. OBJECTIVES: The
      objective of this study was to determine the impact of implementing the NHPPD
      staffing method on 14 nursing-sensitive outcomes: central nervous system
      complications, wound infections, pulmonary failure, urinary tract infection,
      pressure ulcer, pneumonia, deep vein thrombosis, ulcer/gastritis/upper
      gastrointestinal bleed, sepsis, physiologic/metabolic derangement, shock/cardiac
      arrest, mortality, failure to rescue and length of stay. DESIGN AND SETTING: The
      research design was an interrupted time series using retrospective analysis of
      patient and staffing administrative data from three adult tertiary hospitals in
      metropolitan Perth over a 4-year period. SAMPLE: All patient records (N=236,454)
      and nurse staffing records (N=150,925) from NHPPD wards were included. RESULTS:
      The study found significant decreases in the rates of nine nursing-sensitive
      outcomes when examining hospital-level data following implementation of NHPPD;
      mortality, central nervous system complications, pressure ulcers, deep vein
      thrombosis, sepsis, ulcer/gastritis/upper gastrointestinal bleed shock/cardiac
      arrest, pneumonia and average length of stay. At the ward level, significant
      decreases in the rates of five nursing-sensitive outcomes; mortality,
      shock/cardiac arrest, ulcer/gastritis/upper gastrointestinal bleed, length of
      stay and urinary tract infections occurred. CONCLUSIONS: The findings provide
      evidence to support the continuation of the NHPPD staffing method. They also add
      to evidence about the importance of nurse staffing to patient safety; evidence
      that must influence policy. This study is one of the first to empirically review
      a specific nurse staffing method, based on an individual assessment of each ward
      to determine staffing requirements, rather than a "one-size-fits-all" approach.

PMID- 20696430
TI  - Effect of a pedicle-screw-based motion preservation system on lumbar spine
      biomechanics: a probabilistic finite element study with subsequent sensitivity
      analysis.
AB  - Pedicle-screw-based motion preservation systems are often used to support a
      slightly degenerated disc. Such implants are intended to reduce intradiscal
      pressure and facet joints forces, while having a minimal effect on the motion
      patterns. In a probabilistic finite element study with subsequent sensitivity
      analysis, the effects of 10 input parameters, such as elastic modulus and
      diameter of the elastic rod, distraction of the segment, level of bridged
      segments, etc. on the output parameters intervertebral rotations, intradiscal
      pressures, and facet joint forces were determined. A validated finite element
      model of the lumbar spine was employed. Probabilistic studies were performed for
      seven loading cases: upright standing, flexion, extension, left and right lateral
      bending and left and right axial rotation. The simulations show that
      intervertebral rotation angles, intradiscal pressures and facet joint forces are
      in most cases reduced by a motion preservation system. The influence on
      intradiscal pressure is small, except in extension. For many input parameter
      combinations, the values for intervertebral rotations and facet joint forces are
      very low, which indicates that the implant is too stiff in these cases. The
      output parameters are affected most by the following input parameters: loading
      case, elastic modulus and diameter of the elastic rod, distraction of the
      segment, and angular rigidity of the connection between screws and rod. The
      designated functions of a motion preservation system can best be achieved when
      the longitudinal rod has a low stiffness, and when the connection between rod and
      pedicle screws is rigid.

PMID- 20696431
TI  - Use of a polar ionic liquid as second column for the comprehensive two
      dimensional GC separation of PCBs.
AB  - The orthogonality of three columns coupled in two series was studied for the
      congener specific comprehensive two-dimensional GC separation of polychlorinated
      biphenyls (PCBs). A non-polar capillary column coated with poly(5%-phenyl-95%
      methyl)siloxane was used as the first ((1)D) column in both series. A polar
      capillary column coated with 70% cyanopropyl-polysilphenylene-siloxane or a
      capillary column coated with the ionic liquid 1,12
      di(tripropylphosphonium)dodecane bis(trifluoromethane-sulfonyl)imide were used as
      the second ((2)D) columns. Nine multi-congener standard PCB solutions containing
      subsets of all native 209 PCBs, a mixture of 209 PCBs as well as Aroclor 1242 and
      1260 formulations were used to study the orthogonality of both column series.
      Retention times of the corresponding PCB congeners on (1)D and (2)D columns were
      used to construct retention time dependences (apex plots) for assessing
      orthogonality of both columns coupled in series. For a visual assessment of the
      peak density of PCBs congeners on a retention plane, 2D images were compared. The
      degree of orthogonality of both column series was, along the visual assessment of
      distribution of PCBs on the retention plane, evaluated also by Pearson's
      correlation coefficient, which was found by correlation of retention times
      t(R,i,2D) and t(R,i,1D) of corresponding PCB congeners on both column series. It
      was demonstrated that the apolar+ionic liquid column series is almost orthogonal
      both for the 2D separation of PCBs present in Aroclor 1242 and 1260 formulations
      as well as for the separation of all of 209 PCBs. All toxic, dioxin-like PCBs,
      with the exception of PCB 118 that overlaps with PCB 106, were resolved by the
      apolar/ionic liquid series while on the apolar/polar column series three toxic
      PCBs overlapped (105+127, 81+148 and 118+106).

PMID- 20696432
TI  - Identification of chemicals and their metabolites from PHY906, a Chinese medicine
      formulation, in the plasma of a patient treated with irinotecan and PHY906 using
      liquid chromatography/tandem mass spectrometry (LC/MS/MS).
AB  - Traditional Chinese Medicine (TCM) is increasingly being used in combination with
      Western medicine. In general, TCM is comprised of multiple components in sharp
      contrast to Western medicine, where a single active chemical is used. Presently,
      there are no well-established standards for most of the chemical compounds of TCM
      and their respective metabolites. Moreover, there are no formal analytical
      methods for the identification of these chemicals, especially in trace amounts.
      The ability to measure the pharmacokinetic behaviors of chemicals and their
      metabolites from these herbal formulations are critical in understanding of the
      action of TCM. This paper describes the use of LC/MS/MS along with enzyme
      treatments and n-octanol/water partition coefficient, to investigate the chemical
      components of PHY906 and their metabolites in the plasma of a patient with
      metastatic colorectal cancer (mCRC) treated with irinotecan and PHY906. The
      chemicals from an aqueous extract of PHY906 and the plasma from a patient was
      prepared and separated on an Agilent ZORBAX-SB C(18) column, and eluted with
      acetonitrile/0.05% (v/v) formic acid. From the PHY906 aqueous extract, a total of
      57 compounds and 27 metabolites were identified and tentatively assigned
      structures based on their identified mass spectrometry, enzyme digestion and n
      octanol/water partition coefficient. In contrast, analysis of patient plasma
      identified only 33 chemicals and new metabolites. These findings demonstrated
      that LC/MS/MS was and effective and reliable method for studying the parent
      chemicals of the Chinese herbal medicine PHY906 and their metabolites in a
      patient with metastatic colorectal cancer.

PMID- 20696433
TI  - Dynamic supported liquid membrane tip extraction of glyphosate and
      aminomethylphosphonic acid followed by capillary electrophoresis with contactless
      conductivity detection.
AB  - A dynamic supported liquid membrane tip extraction (SLMTE) procedure for the
      effective extraction and preconcentration of glyphosate (GLYP) and its metabolite
      aminomethylphosphonic acid (AMPA) in water has been investigated. The SLMTE
      procedure was performed in a semi-automated dynamic mode and demonstrated a
      greater performance against a static extraction. Several important extraction
      parameters such as donor phase pH, cationic carrier concentration, type of
      membrane solvent, type of acceptor stripping phase, agitation and extraction time
      were comprehensively optimized. A solution of Aliquat-336, a cationic carrier, in
      dihexyl ether was selected as the supported liquid incorporated into the membrane
      phase. Quantification of GLYP and AMPA was carried out using capillary
      electrophoresis with contactless conductivity detection. An electrolyte solution
      consisting of 12 mM histidine (His), 8 mM 2-(N-morpholino)ethanesulfonic acid
      (MES), 75 microM cetyltrimethylammonium bromide (CTAB), 3% methanol, pH 6.3, was
      used as running buffer. Under the optimum extraction conditions, the method
      showed good linearity in the range of 0.01-200 microg/L (GLYP) and 0.1-400
      microg/L (AMPA), acceptable reproducibility (RSD 5-7%, n=5), low limits of
      detection of 0.005 microg/L for GLYP and 0.06 microg/L for AMPA, and satisfactory
      relative recoveries (90-94%). Due to the low cost, the SLMTE device was disposed
      after each run which additionally eliminated the possibility of carry-over
      between runs. The validated method was tested for the analysis of both analytes
      in spiked tap water and river water with good success.

PMID- 20696434
TI  - Comparison of orthogonal liquid and gas chromatography-mass spectrometry
      platforms for the determination of amino acid concentrations in human plasma.
AB  - Concentrations of amino acids in a human plasma pool were determined using four
      independent quantification methods. Orthogonal separation schemes (LC, GC, or GC
      x GC) and detection systems (triple quadrupole or time-of-flight mass
      spectrometry) are shown to demonstrate excellent consistency among platforms for
      quantifying 18 amino acids in NIST Standard Reference Material (SRM) 1950
      Metabolites in Human Plasma using a well-characterized isotope dilution (ID)
      quantification method. Measured levels were consistent with reference values in
      plasma from the literature. Individual amino acid concentrations in plasma varied
      by over an order of magnitude ranging from 1.83 microg/g to 28.0 microg/g (7.78
      micromol/L to 321 micromol/L). Average variability (coefficient of variation)
      between experimental amino acid concentrations (excluding cysteine) among all
      methods was 6.3%. Certified mass fraction values for amino acids in NIST SRM 1950
      will be established from statistically weighted means of all experimental
      results.

PMID- 20696435
TI  - Discussion on "A comprehensive two-dimensional gas chromatography coupled with
      quadrupole mass spectrometry approach for identification of C10 derivatives from
      decalin" by C. Flego, N. Gigantiello, W.O. Parker, Jr., V. Calemma [J.
      Chromatogr. A 1216 (2009) 2891].

PMID- 20696436
TI  - Analysis of amprolium by hydrophilic interaction liquid chromatography-tandem
      mass spectrometry.
AB  - We present a fast liquid chromatography-tandem mass spectrometry (LC-MS/MS)
      method for the analysis of the coccidiostat amprolium in food samples. Tandem
      mass spectrometry in a triple quadrupole was used for quantitative purposes, and
      the information from multiple-stage mass spectrometry in an ion-trap mass
      analyzer contributed to fragmentation studies. Hydrophilic interaction liquid
      chromatography (HILIC) in a Fused-Core column using isocratic elution
      (acetonitrile:formic acid/ammonium formate buffer pH 4, 50 mM (60:40))
      successfully analyzed this compound in less than 3 min. The HILIC system was
      coupled to heated electrospray-MS/MS using highly selective-selected reaction
      monitoring (H-SRM) to improve sensitivity and selectivity for the analysis of
      amprolium, after a simple sample treatment based on an "extract and shoot"
      strategy. Accurate mass measurements were performed to identify the interfering
      compound responsible for causing matrix ion enhancement in the signal of
      amprolium. The addition of l-carnitine (the interfering compound) (1 microg L(
      1)) to standards and sample extracts allowed the use of the external calibration
      method for quantitative purposes. The LC-MS/MS (H-SRM) method showed good
      precision (relative standard deviation, RSD, lower than 13%), accuracy and
      linearity and allowed the determination of amprolium down to the ppb level (LODs
      between 0.1 and 0.6 microg kg(-1)).

PMID- 20696437
TI  - Facile preparation of gold nanoparticles through autoreduction of gold ions in
      the presence of fluoroalkyl end-capped cooligomeric aggregates: LCST-triggered
      sol-gel switching behavior of novel thermoresponsive fluoroalkyl end-capped
      cooligomeric nanocomposite-encapsulated gold nanoparticles.
AB  - Thermosensitive fluoroalkyl end-capped N-(1,1-dimethyl-3-oxobutyl)acrylamide
      acryloylmorpholine cooligomer, which was prepared by the cooligomerization of
      fluoroalkanoyl peroxide with the corresponding monomers, was applied to the
      autoreduction of gold ions to afford the fluorinated cooligomeric nanocomposite
      encapsulated gold nanoparticles under very mild conditions; although the
      corresponding non-fluorinated cooligomer was not able to afford the gold
      nanoparticles at all under similar conditions. These fluorinated cooligomeric
      nanocomposites exhibited a plasmon absorption band around 520 nm related to the
      formation of gold nanoparticles in their aqueous solutions. Interestingly, these
      fluorinated nanocomposite-encapsulated gold nanoparticles can exhibit the
      thermoswitchable sol-gel transition through the lower critical solution
      temperature (LCST)-triggered aggregation of the corresponding nanocomposites, and
      this sol-gel switching behavior is reversible during a heating and cooling cycle.

PMID- 20696438
TI  - Mercury partition in the interface between a contaminated lagoon and the ocean:
      the role of particulate load and composition.
AB  - After having estimated the patterns of flow to the ocean and found some seasonal
      and tidal differences, mainly with regard to the relative importance of dissolved
      and particulate fractions, mercury partitioning at the interface between a
      contaminated lagoon and the Atlantic Ocean was investigated during four tidal
      cycles in contrasting season and tidal regimes. Mercury was found to be located
      predominantely in the particulate fraction throughout the year, contributing to
      its retention within the system. Seasonal conditions, variations in marine and
      fluvial signals and processes affecting bed sediment resuspension influenced the
      character and concentration of suspended particulate matter in the water column.
      Variation in the nature, levels and partitioning of organic carbon in the
      particulate fraction affected levels of particulate mercury as well as mercury
      partitioning. These results highlight the dominant role of suspended particulate
      matter in the distribution of anthropogenic mercury and reinforce the importance
      of competitive behavior related to organic carbon in mercury scavenging.

PMID- 20696439
TI  - Daily availability of nutrients and metals in a eutrophic meso-tidal coastal
      lagoon (Obidos lagoon, Portugal).
AB  - This baseline reports daily variations of physico-chemical parameters, nutrients
      and metals in water of two sites [eutrophic conditions (BB) versus reference
      (LL)] in Obidos coastal lagoon (Portugal). Dissolved oxygen in BB varied between
      40% saturation levels (night) and 190% (daylight). NH(4)(+), PO(4)(3-) and ratios
      to Al of Mn, Fe and Pb in suspended particulate matter increased during the
      period of lower oxygenation, indicating exportation of nutrients and metals from
      the sediment to water at night. At LL, O(2) values oscillated always around 100%.
      PO(4)(3-) and Mn/Al ratio at LL were always lower than at BB and no increases
      were found during the night. The input of PO(4)(3-) and Mn provided from the
      sediment at BB during the night could surpass the contribution of freshwater
      discharges. PCA confirmed the separation of most samples from BB and LL. These
      results pointed to the importance of assessing chemical conditions over day-night
      cycles.

PMID- 20696440
TI  - Challenges associated with pre-border management of biofouling on oil rigs.
AB  - The potential for oil rigs to transport diverse, reef-like communities around the
      globe makes them high risk vectors for the inadvertent spread of non-indigenous
      species (NIS). This paper describes two case studies where a suite of pre-border
      management approaches was applied to semi-submersible drilling rigs. In the first
      case study, a drilling rig was defouled in-water prior to departure from New
      Zealand to Australia. Risk mitigation measures were successful in reducing
      biosecurity risks to the recipient region, but they resulted in the unintentional
      introduction of the non-indigenous brown mussel (Perna perna) to New Zealand when
      the rig was defouled in-water by divers. In the second case study, lessons
      learned from this high-profile incursion resulted in a more structured approach
      to pre-border management, and this serves as a useful template for future rig
      transfers.

PMID- 20696441
TI  - Biomonitoring of organochlorine compounds and trace metals along the Eastern
      Adriatic coast (Croatia) using Mytilus galloprovincialis.
AB  - The paper presents the results of monitoring trace organic contaminants (17 PCBs
      and 7 OCPs) and 6 trace metals (Cd, Cr, Cu, Hg, Pb and Zn) in the coastal waters
      of the eastern Adriatic in 2006 using Mytilus galloprovincialis as indicator
      species. OCPs were found in all samples (0.07-14.3 ng g(-1)d.wt.), while in
      positive samples concentrations of PCBs ranged between 0.16 and 20.5 ng g(
      1)d.wt. The alpha-HCH/gamma-HCH and DDE/DDT ratios indicated recent input of
      gamma-HCH and DDT. Spatial distributions of HCB, PCBs, DDTs and Hg were
      significantly correlated with population density. Although elevated
      concentrations of all trace metals and organic contaminants were recorded in the
      densely populated and industrialized areas, overall data point to relatively low
      level of contamination of the eastern Adriatic coast. Evaluation of the risks to
      human health associated with consumption of the mussels suggested that there is
      no health risk for moderate shellfish consumers.

PMID- 20696442
TI  - Benthic foraminiferal assemblages from Moreton Bay, South-East Queensland,
      Australia: applications in monitoring water and substrate quality in subtropical
      estuarine environments.
AB  - We assess species composition, assemblage structure and distribution of the
      benthic foraminiferal assemblages from diverse substrates in Moreton Bay, South
      East Queensland, Australia. Analysis of 47 surface sediment samples revealed 69
      species, three distinct foraminiferal assemblages and six sub-assemblages. The
      assemblages from the western Bay are characterized by stress tolerant taxa and
      the lowest diversity, whereas the assemblages from the eastern Bay are
      characterized by symbiont-bearing taxa and high diversity. We found a correlation
      between foraminiferal assemblages and substrate conditions that was indicative of
      strong environmental gradients (substrate type, water quality and salinity), from
      an urban-impacted assemblage in the westernmost part of the Bay, to a hyposaline,
      estuarine-influenced assemblage in the western Bay to a nearly normal marine to
      hypersaline assemblage in the eastern Bay. The FORAM Index was consistent with
      the changes in water and sediment quality gradient, from the western shoreline to
      the eastern Bay. Thus the foraminiferal assemblages of Moreton Bay make excellent
      bio-indicators of environmental changes in a subtropical, estuarine setting in
      eastern Australia.

PMID- 20696443
TI  - Association of metals with plastic production pellets in the marine environment.
AB  - Plastic production pellets sampled from four beaches along a stretch of coastline
      (south Devon, SW England) and accompanying, loosely adhered and entrapped
      material removed ultrasonically have been analysed for major metals (Al, Fe, Mn)
      and trace metals (Cu, Zn, Pb, Ag, Cd, Co, Cr, Mo, Sb, Sn, U) following acid
      digestion. In most cases, metal concentrations in composite pellet samples from
      each site were less than but within an order of magnitude of corresponding
      concentrations in the pooled extraneous materials. However, normalisation of data
      with respect to Al revealed enrichment of Cd and Pb in plastic pellets at two
      sites. These observations are not wholly due to the association of pellets with
      fine material that is resistant to ultrasonication since new polyethylene pellets
      suspended in a harbour for 8 weeks accumulated metals from sea water through
      adsorption and precipitation. The environmental implications and potential
      applications of these findings are discussed.

PMID- 20696444
TI  - [Body mass index as prognostic factor in patients after a first myocardial
      infarction].

PMID- 20696445
TI  - Sucrose: metabolite and signaling molecule.
AB  - Sucrose is a molecule that is synthesized only by oxygenic photosynthetic
      organisms. In plants, sucrose is synthesized in source tissues and then can be
      transported to sink tissues, where it is utilized or stored. Interestingly,
      sucrose is both a metabolite and a signaling molecule. Manipulating the rate of
      the synthesis, transport or degradation of sucrose affects plant growth,
      development and physiology. Altered sucrose levels changes the quantity of
      sucrose derived metabolites and sucrose-specific signaling. In this paper, these
      changes are summarized. Better understanding of sucrose metabolism and sucrose
      sensing systems in plants will lead to opportunities to adapt plant metabolism
      and growth.

PMID- 20696446
TI  - Bioelectrical impedance analysis determination of water content and distribution
      in the horse.
AB  - A horse's hydration status is critical to its health. The accurate and
      quantitative determination of it has been problematic because of size, length and
      density of hair, and uneven topography. The objective of this study was to
      validate a bioelectrical impedance analysis (BIA) method for objectively
      quantifying hydration status. Monofrequency BIA values and simple biometric
      measurements were used to construct predictive equations for total body water,
      plasma, extracellular, and intra-cellular fluid volumes. These predictive
      equations were correlated with standard body fluid dilution reference methods.
      The result was an accuracy of +/-0.64% for total body water, +/-0.17% for plasma
      volume, +/-1.91% for extra-cellular fluid, and +/-0.57% for intra-cellular fluid
      compartments. Less than 5 min was required for all of the measurements and
      determinations. Therefore, it appears that an accurate measurement of body fluid
      distribution can be performed on horses using a fast, easy, non-invasive,
      inexpensive BIA method.

PMID- 20696447
TI  - Disodium-fosfomycin pharmacokinetics and bioavailability in post weaning piglets.
AB  - Disodium-fosfomycin pharmacokinetics has been studied in different species after
      oral, intravenous, intramuscular and subcutaneous administration. At present
      there are neither documented clinical experiences of the use of fosfomycin in
      pigs nor any published studies in weaning piglets, although it is a period of
      high incidence of infectious diseases. The pharmacokinetics and the
      bioavailability of sodium fosfomycin were studied in post weaning piglets after
      intravenous and intramuscular administration of 15 mg/kg of body weight. Plasma
      concentrations were measured by a high-performance liquid ms/ms. After IV
      administration the area under the fosfomycin concentration:time curve in plasma
      was AUC(0-12) of 120.00 +/- 23.12 MUg h/ml and the volume of distribution (Vd) of
      273.00 +/- 40.70 ml/kg. The elimination was rapid with a plasma clearance of
      131.50 +/- 30.07 ml/kg/h and a T(1/2) of 1.54 +/- 0.40 h. Peak serum
      concentration (Cmax), Tmax, AUC(0-12) and bioavailability for the IM
      administration were 43.00 +/- 4.10 MUg/ml, 0.75 +/- 0.00 h, 99.00 +/- 0.70 MUg
      h/ml and 85.5 +/- 9.90% respectively. Different authors have determined a minimum
      inhibitory concentration (MIC90) ranging from 0.25 MUg/ml for Streptococcus sp.
      and 0.5 MUg/ml for Escherichia coli. Considering the above, and according to the
      values of plasma concentration vs time profiles observed in this study, effective
      plasma concentrations of fosfomycin for sensitive bacteria can be obtained
      following IV and IM administration of 15 mg/kg in piglets.

PMID- 20696448
TI  - Reconstruction of 3D ultrasound images based on Cyclic Regularized Savitzky-Golay
      filters.
AB  - This paper presents a new three-dimensional (3D) ultrasound reconstruction
      algorithm for generation of 3D images from a series of two-dimensional (2D) B
      scans acquired in the mechanical linear scanning framework. Unlike most existing
      3D ultrasound reconstruction algorithms, which have been developed and evaluated
      in the freehand scanning framework, the new algorithm has been designed to
      capitalize the regularity pattern of the mechanical linear scanning, where all
      the B-scan slices are precisely parallel and evenly spaced. The new
      reconstruction algorithm, referred to as the Cyclic Regularized Savitzky-Golay
      (CRSG) filter, is a new variant of the Savitzky-Golay (SG) smoothing filter. The
      CRSG filter has been improved upon the original SG filter in two respects: First,
      the cyclic indicator function has been incorporated into the least square cost
      function to enable the CRSG filter to approximate nonuniformly spaced data of the
      unobserved image intensities contained in unfilled voxels and reduce speckle
      noise of the observed image intensities contained in filled voxels. Second, the
      regularization function has been augmented to the least squares cost function as
      a mechanism to balance between the degree of speckle reduction and the degree of
      detail preservation. The CRSG filter has been evaluated and compared with the
      Voxel Nearest-Neighbor (VNN) interpolation post-processed by the Adaptive Speckle
      Reduction (ASR) filter, the VNN interpolation post-processed by the Adaptive
      Weighted Median (AWM) filter, the Distance-Weighted (DW) interpolation, and the
      Adaptive Distance-Weighted (ADW) interpolation, on reconstructing a synthetic 3D
      spherical image and a clinical 3D carotid artery bifurcation in the mechanical
      linear scanning framework. This preliminary evaluation indicates that the CRSG
      filter is more effective in both speckle reduction and geometric reconstruction
      of 3D ultrasound images than the other methods.

PMID- 20696449
TI  - Design of a Bezier-profile horn for high displacement amplification.
AB  - A new horn for high displacement amplification is developed. The profile of the
      horn is a cubic Bezier curve. The ultrasonic actuation of the horn exploits the
      first longitudinal displacement mode of the horn. A design method of the horn
      using an optimization scheme and finite element analyses is developed. Prototypes
      of the horns are manufactured by a numerical control machining process.
      Performances of the proposed horn have been evaluated by experiments.
      Experimental results of the harmonic response of the fabricated horn confirm the
      effectiveness of the design method. The displacement amplification of the
      proposed horn is 71% higher than that of the traditional catenoidal horn with the
      same length and end surface diameters.

PMID- 20696450
TI  - Analysis of the function of cytoplasmic fibers formed by the rubella virus
      nonstructural replicase proteins.
AB  - The P150 and P90 replicase proteins of rubella virus (RUBV), a plus-strand RNA
      Togavirus, produce a unique cytoplasmic fiber network resembling microtubules.
      Pharmacological and mutagenic approaches were used to determine if these fibers
      functioned in virus replication. The pharmacological approach revealed that
      microtubules were required for fiber formation, but neither was necessary for
      virus replication. Through the mutagenic approach it was found that alpha-helices
      near both termini of P150 were necessary for fiber assembly and infectivity, but
      fiber formation and viability could not be correlated because most of these
      mutations were lethal. The N-terminal alpha-helix of P150 affected both
      proteolytic processing of P150 and P90 from the P200 precursor and targeting of
      P200, possibly through directing conformational folding of P200. Finally, we made
      the unexpected discovery that RUBV genomes can spread from cell-to-cell without
      virus particles, a process that we hypothesize utilizes RUBV-induced cytoplasmic
      projections containing fibers and replication complexes.

PMID- 20696451
TI  - Overnight stagnation of drinking water in household taps induces microbial growth
      and changes in community composition.
AB  - Drinking water quality is routinely monitored in the distribution network but not
      inside households at the point of consumption. Fluctuating temperatures,
      residence times (stagnation), pipe materials and decreasing pipe diameters can
      promote bacterial growth in buildings. To test the influence of stagnation in
      households on the bacterial cell concentrations and composition, water was
      sampled from 10 separate households after overnight stagnation and after flushing
      the taps. Cell concentrations, measured by flow cytometry, increased (2-3-fold)
      in all water samples after stagnation. This increase was also observed in
      adenosine tri-phosphate (ATP) concentrations (2-18-fold) and heterotrophic plate
      counts (4-580-fold). An observed increase in cell biovolume and ATP-per-cell
      concentrations furthermore suggests that the increase in cell concentrations was
      due to microbial growth. After 5 min flushing of the taps, cell concentrations
      and water temperature decreased to the level generally found in the drinking
      water network. Denaturing gradient gel electrophoresis also showed a change in
      the microbial composition after stagnation. This study showed that water
      stagnation in household pipes results in considerable microbial changes. While
      hygienic risk was not directly assessed, it emphasizes the need for the
      development of good material validation methods, recommendations and spot tests
      for in-house water installations. However, a simple mitigation strategy would be
      a short flushing of taps prior to use.

PMID- 20696452
TI  - Influence of water quality on the presence of off-flavour compounds (geosmin and
      2-methylisoborneol).
AB  - Geosmin and 2-methylisoborneol are off-flavour compounds related to poor
      organoleptics and a decrease in consumer satisfaction with drinking water. The
      relationship between these off-flavour compounds and 39 parameters of water
      quality (chemical, physical and biological) for three different surface waters
      from lotic systems that supply potable water to Quebec City and Levis (Canada)
      was studied using principal component analysis. The objective of this study was
      to show that a multidimensional approach with principal component analysis using
      the component matrix serves to differentiate the processes involved in the
      appearance of the olfactory compounds from those not involved or little involved
      and to extract the most representative data of these processes. Our study shows
      that the presence of geosmin can be explained, in the case of the water studied,
      by a process associated primarily with the eutrophication of water and, to a
      lesser degree, by an allochthonous origin. However, the presence of 2
      methylisoborneol may be linked to two processes with different origins, but of
      equal importance: a winter origin - most likely allochthonous - involving
      anthropic contributions and an autochthonous bacterial origin.

PMID- 20696453
TI  - Contributions of wastewater, runoff and sewer deposit erosion to wet weather
      pollutant loads in combined sewer systems.
AB  - An observatory of urban pollutants was created in Paris for the purpose of
      assessing the dynamics of wastewater and wet weather flow (WW and WWF) pollutant
      loads within combined sewers. This observatory is composed of six urban
      catchments, covering land areas ranging in size from 42 ha to 2581 ha. For a wide
      array of parameters including total suspended solids (TSS), chemical and
      biochemical oxygen demand (COD and BOD(5)), total organic carbon (TOC), total
      Kjeldahl nitrogen (TKN), heavy metals (Cu and Zn) and polycyclic aromatic
      hydrocarbons (PAHs), this article is intended to evaluate the contributions of
      wastewater, runoff and in-sewer processes to WWF pollutant loads through the use
      of an entry-exit mass balance approach. To achieve this objective, a total of 16
      rain events were sampled on these sites between May 2003 and February 2006. This
      study has confirmed that at the considered catchment scale (i.e. from 42 ha to
      2581 ha) the production and transfer processes associated with WWF pollutant
      loads do not vary with basin scale. Entry-exit chemical mass balances over all
      catchments and for a large number of rain events indicate that wastewater
      constitutes the main source of organic and nitrogenous pollution, while runoff is
      the predominant source of Zn. For Cu, PAHs and TSS, the calculation underscores
      the major role played by in-sewer processes, specifically by sediment erosion, as
      a source of WWF pollution. A significant loss of dissolved metals was also
      observed during their transfer within the sewer network, likely as a consequence
      of the adsorption of dissolved metals on TSS and/or on sewer deposits. Moreover,
      the nature of eroded particles was examined and compared to the various sewer
      deposits. This comparison has highlighted that such particles exhibit similar
      organic and PAH contents to those measured in the organic layer, thus suggesting
      that the deposit eroded during a wet weather period is organic and of a nature
      comparable to the organic layer. Despite the extent of initial field
      investigations, no organic deposit was observed to be present on sewer lines
      within the catchments, which implies that this organic deposit is probably
      present in another form or to be found elsewhere in the main trunks.

PMID- 20696454
TI  - Methane production from oleate: assessing the bioaugmentation potential of
      Syntrophomonas zehnderi.
AB  - The potential for improving long-chain fatty acids (LCFA) conversion to methane
      was evaluated by bioaugmenting a non-acclimated anaerobic granular sludge with
      Syntrophomonas zehnderi. Batch bioaugmentation assays were performed with and
      without the solid microcarrier sepiolite, using 1 mM oleate as sole carbon and
      energy source. When S. zehnderi was added to the anaerobic sludge methane
      production from oleate was faster. High methane yields, i.e. 89 +/- 5% and 72 +/-
      1%, were observed in bioaugmented assays in the absence and presence of
      sepiolite, respectively. Sepiolite stimulated a faster methane production from
      oleate and prevented the accumulation of acetate. Acetoclastic activity was
      affected by oleate in the absence of sepiolite, where methane production rate was
      26% lower than in assays with microcarrier.

PMID- 20696455
TI  - Challenges in determining causation in structure-function studies using molecular
      biological techniques.
AB  - The use of molecular biological techniques for determining the levels and types
      of different microbial populations in bioreactors has led to the emergence of the
      microbial community 'structure-function' paradigm that is often used in research.
      Typically, lab- or full-scale systems are monitored for the relevant parameters,
      and these parameters are related to the changes in microbial populations.
      Research in activated sludge phenomena, such as filamentous bulking, filamentous
      foaming, nitrogen removal, and phosphorus removal, are replete with many examples
      of this 'structure-function' paradigm, most commonly those that involve 16S rRNA
      gene-based analysis of the microbial populations. In many cases, such studies
      assume a causal microbial population (e.g., a species that causes bulking or
      foaming), or conclude in identifying a causal population. However, assigning
      cause to specific organisms and populations is problematic in a complex
      environment such as wastewater bioreactors. The Koch-Henle postulates, the gold
      standard in evaluating causation of disease, have limitations when applied to
      systems with mixed microbial communities with complex interactions, particularly
      if pure cultures are not available. Molecular techniques that allow specific
      identification and quantification of organisms have been used by researchers to
      overcome the limitations of culture-based techniques, and at the same time,
      raised new questions on the applicability of causation postulates in
      environmental systems. In this paper, various causation criteria improving on the
      Koch-Henle postulates are presented. Complicating issues in assigning cause in
      wastewater bioreactors are identified. Approaches for determining cause-effect
      relationships are illustrated using 16S rDNA-based investigations of filaments
      that cause bulking and foaming in activated sludge. The hope is that a causation
      framework that accounts for the assumptions in molecular studies, as applied to
      wastewater treatment research, will lead to improved experimental design and
      analysis of data.

PMID- 20696456
TI  - Effect of polymeric substrate on sludge settleability.
AB  - The study aims to evaluate the role of a polymeric substrate (starch) on sludge
      settleability. Despite being an important COD component of the wastewater, the
      relationship between polymeric substrates and bulking sludge has been hardly
      studied. The polymers are hydrolysed at a rate smaller than the consumption rate
      of monomers. This means that the soluble substrate resulting from hydrolysis is
      likely to be present at growth rate limiting concentrations. According to the
      kinetic selection theory this leads to bulking sludge. However, a recently
      postulated theory suggests that, strong diffusion limited micro-gradients of
      substrate concentration inside flocs lead to bulking sludge, and not a low
      substrate concentration as such. If the polymeric COD is first incorporated in
      the sludge floc and afterwards hydrolysed in the sludge floc then there is
      essentially no substrate gradient inside the biological flocs. The experiments
      showed that conditions leading to bulking sludge with monomers (glucose) did not
      lead to bulking when starch was used. A bulking sludge event was even cured just
      by substituting the monomer with starch. These results are clearly in line with a
      diffusion gradient--based theory for bulking sludge. Nevertheless, flocs growing
      on starch are more open, fluffy and porous than flocs formed on maltose or
      glucose, most likely because the starch needs to be hydrolysed at the surface of
      the micro-colonies forming the flocculated sludge. Some additional observations
      on occurrence of filamentous bacteria in oxygen diffusion limited systems are
      also discussed in this manuscript.

PMID- 20696457
TI  - Arsenic association and stability in long-term disposed arsenic residues.
AB  - Long-term stability of arsenic residues is investigated by determining arsenic
      phases remaining in gold mining residues after two decades of impoundment. The
      residues, generated by arsenic coprecipitation with iron and lime, were disposed
      of in-lined sites for 9-16 years (pit C) and 16-23 years (pits A and B). Arsenic
      is present in the residues as As(V) species, predominantly in the form of
      amorphous iron arsenate (55-75% As(total,) pits A and B; 55-70% As(total), pit C)
      and sorbed onto amorphous iron-oxyhydroxides (20-33% As(total), pits A and B; 22
      37% As(total), pit C). The presence of minor Ca-arsenate phases (undefined
      composition) and Al-arsenate coprecipitates is also indicated. The passive
      enrichment of iron in pits A and B, and the relative low concentration of
      calcium, sulfur and arsenic if compared to those of pit C, suggest that a soluble
      Ca-arsenate phase (e.g. CaHAsO(4).H(2)O), a fraction of gypsum and As(III) were
      dissolved along 16-23 years of residue disposal. The presence of As(V) only and
      excess iron demonstrates the importance of the oxidation state and high Fe/As
      ratio on long-term stability of arsenic residues.

PMID- 20696458
TI  - Monitoring techniques for odour abatement assessment.
AB  - Odorous emissions from sewers and wastewater treatment plants are a complex
      mixture of volatile chemicals that can cause annoyance to local populations,
      resulting in complaints to wastewater operators. Due to the variability in
      hedonic tone and chemical character of odorous emissions, no analytical technique
      can be applied universally for the assessment of odour abatement performance.
      Recent developments in analytical methodologies, specifically gas chromatography,
      odour assessment approaches (odour wheels, the odour profile method and dynamic
      olfactometry), and more recently combined gas chromatography-sensory analysis,
      have contributed to improvements in our ability to assesses odorous emissions in
      terms of odorant concentration and composition. This review collates existing
      knowledge with the aim of providing new insight into the effectiveness of
      sensorial and characterisation approaches to improve our understanding of the
      fate of odorous emissions during odour abatement. While research in non-specific
      sensor array (e-nose) technology has resulted in progress in the field of
      continuous odour monitoring, more successful long term case-studies are still
      needed to overcome the early overoptimistic performance expectations. Knowledge
      gaps still remain with regards to the decomposition of thermally unstable
      volatile compounds (especially sulfur compounds), the inability to predict
      synergistic, antagonistic, or additive interactions among odorants in combined
      chemical/sensorial analysis techniques, and the long term stability of chemical
      sensors due to sensor drift, aging, temperature/relative humidity effects, and
      temporal variations. Future odour abatement monitoring will require the
      identification of key odorants to facilitate improved process selection, design
      and management.

PMID- 20696459
TI  - Absolute kinetics and reaction efficiencies of hydroxyl-radical-induced
      degradation of methyl isothiocyanate (MITC) in different quality waters.
AB  - Methyl isothiocyanate (MITC), a toxic and corrosive skin and respiratory
      irritant, is a common soil fumigant byproduct which has become an atmospheric,
      aqueous, and soil contaminant. The work described here examines the degradation
      and potential removal of MITC from contaminated waters via free radical
      reactions. We have measured the oxidizing hydroxyl radical ((.)OH) reaction rate
      constant with MITC over a range of temperatures relevant to wastewater treatment
      conditions, determining a room temperature value of (5.69+/-0.56) x 10(8)M(-1)s(
      1) and a corresponding Arrhenius activation energy of 12.90+/-0.82 kJ mol(-1).
      Hydroxyl radical reaction efficiencies with MITC in pure water, an associated
      matrix of model real-world waters, and a reverse osmosis permeate water have also
      been determined. While solutions containing these constituents had significantly
      decreased MITC removal efficiencies (5.5-14.7%) as compared to pure water (54.4+/
      3.4%), relative rate calculation corrections showed that the (.)OH radical
      efficiencies for solutions containing DOM were the same as in pure water.
      However, the slightly higher efficiencies for carbonate-containing solutions
      indicated that some additional MITC degradation occurred from carbonate radical
      reactions.

PMID- 20696460
TI  - Sublethal levels of cadmium down-regulate the gene expression of DNA mismatch
      recognition protein MutS homolog 6 (MSH6) in zebrafish (Danio rerio) embryos.
AB  - MutS homolog 6 (MSH6) is the major mismatch contacting component of the MSH2-MSH6
      heterodimeric complex (MutSalpha) that mediates DNA mismatch repair (MMR) of
      simple mispairs and small insertion-deletion loops in eukaryotes. This study
      examined the potential of cadmium (Cd) to disturb the gene expression of MSH6 in
      vertebrates using zebrafish (Danio rerio) embryo as a model organism.
      Semiquantitative RT-PCR indicated that msh2 and msh6 expressions were suppressed
      in embryos at 1h post fertilization (hpf), then drastically up-regulated in 2 hpf
      embryos and actively expressed in 3-25 hpf embryos. In the presence of a
      constitutive beta-actin expression, exposure of 1 hpf embryos to sublethal
      concentrations of CdCl(2) at 0.5-3 MUM for 4 or 9h caused a time and
      concentration-dependent down-regulation of msh6 transcription. Cd failed to
      inhibit msh2 transcription except at 3 MUM, reflecting the higher sensitivity of
      msh6 than msh2 transcription to Cd. Whole mount in situ hybridization showed a
      wide distribution of msh6 transcripts in the front body portions of 10 hpf
      embryos and Cd-induced a general suppression of msh6 expression in zebrafish
      tissues. Cd-induced down-regulation of msh6 transcription paralleled with reduced
      levels of MSH6 protein synthesis and MSH6-mediated G-T mismatch binding
      activities identified by band shift assay using recombinant zebrafish MSH6 and an
      anti-human MSH6 antibody. Our results revealed the inhibition of Cd on MSH6
      expression at both mRNA and protein levels and this mechanism may play a role in
      Cd genotoxicity.

PMID- 20696461
TI  - Relevance of urban glyphosate use for surface water quality.
AB  - Relative contributions of agricultural and urban uses to the glyphosate
      contamination of surface waters were studied in a small catchment (25 km(2)) in
      Switzerland. Monitoring in four sub-catchments with differing land use allowed
      comparing load and input dynamics from different sources. Agricultural as well as
      urban use was surveyed in all sub-catchments allowing for a detailed
      interpretation of the monitoring results. Water samples from the river system and
      from the urban drainage system (combined sewer overflow, storm sewer and outflow
      of wastewater treatment plant) were investigated. The concentrations at peak
      discharge during storm events were elevated throughout the year with maximum
      concentrations of 4.15 MUg L(-1). Glyphosate concentrations mostly exceeded those
      of other commonly used herbicides such as atrazine or mecoprop. Fast runoff from
      hard surfaces led to a fast increase of the glyphosate concentration shortly
      after the beginning of rainfall not coinciding with the concentration peak
      normally observed from agricultural fields. The comparison of the agricultural
      application and the seasonal concentration and load pattern in the main creek
      from March to November revealed that the occurrence of glyphosate cannot be
      explained by agricultural use only. Extrapolations from agricultural loss rates
      and from concentrations found in the urban drainage system showed that more than
      half of the load during selected rain events originates from urban areas. The
      inputs from the effluent of the wastewater treatment plant, the overflow of the
      combined sewer system and of the separate sewer system summed up to 60% of the
      total load.

PMID- 20696462
TI  - Bioindication capacity of metal pollution of native and transplanted Pleurozium
      schreberi under various levels of pollution.
AB  - During a period of 90d assays were carried out with the moss Pleurozium schreberi
      transplanted from an uncontaminated control site to 27 sites selected in one of
      the most polluted regions of Upper Silesia (Poland). The native mosses of this
      species were collected from the polluted sites. Concentrations of Cd, Cr, Cu, Pb
      and Zn were determined in P. schreberi and in the soil of all of the sites. The
      sites were divided into more and less polluted ones. The obtained results
      indicate that the native P. schreberi from the more polluted sites accumulated
      significantly more Cd, Cr, Cu, Pb and Zn than the transplanted moss from the same
      sites. The transplanted P. schreberi from the less polluted sites accumulated
      significantly more Cr, Pb, Zn, significantly less Cu and comparable amounts of
      Cd, as compared to the native moss. The selection of native versus transplant P.
      schreberi as a bioindicator depends on the level of pollution.

PMID- 20696463
TI  - Assessment of the impact of the vehicular traffic on BTEX concentration in ring
      roads in urban areas of Bari (Italy).
AB  - A BTEX monitoring campaign, consisting of two weekly periods, was carried out in
      Bari, south-eastern Italy, in order to evaluate the impact of the vehicular
      traffic on the air quality at the main access roads of the city. Twenty-one
      sampling sites were selected: the pollution produced by the traffic in the
      vicinity of all exits from the ring road and some access roads to the city, those
      with higher traffic density, were monitored. Contemporarily the main
      meteorological parameters (ambient temperature, wind, atmospheric pressure and
      natural radioactivity) were investigated. It was found that in the same traffic
      conditions, barriers, buildings and local meteorological conditions can have
      important effects on the atmospheric dispersion of pollutants. This situation is
      more critical in downtown where narrow roads and high buildings avoid an
      efficient dispersion producing higher levels of BTEX. High spatial resolution
      monitoring allowed both detecting the most critical areas of the city with high
      precision and obtaining information on the mean level of pollution, meaning air
      quality standard of the city. The same concentration pattern and the correlation
      among BTEX levels in all sites confirmed the presence of a single source, the
      vehicular traffic, having a strong impact on air quality.

PMID- 20696464
TI  - Toxicity of coal-tar and asphalt sealants to eastern newts, Notophthalmus
      viridescens.
AB  - Between 1970 and 2000 the concentration of total polycyclic aromatic hydrocarbons
      (TPAH) in several lakes across the country increased whereas those of other
      persistent organic pollutants (POPs) tended to remain stable or declined.
      Urbanized watersheds experienced greater rises in TPAH concentration compared to
      non-urban lakes. Sources for urban PAHs include industrial wastes, vehicular
      exhausts and oil leaks and sealants from pavement surfaces. Both coal-tar and
      asphalt sealants are used to protect surfaces but runoff from surfaces coated
      with coal-tar can have mean concentrations of 3500 mg TPAHs kg(-1), much higher
      than runoff from asphalt-sealed or cement surfaces. Unaltered parent compounds of
      PAHs can have many lethal and sublethal toxic effects, but oxidation and UV
      radiation can alter the toxicity of these compounds, sometimes creating
      degradates that are many times more toxic than parent compounds. The purposes of
      this study were to determine if coal-tar sealants can be toxic to adult eastern
      newts (Notophthalmus viridescens) and to compare the toxicity of coal-tar sealant
      to that of asphalt sealant. Newts were exposed to sediments containing dried
      sealants ranging from 0 mg kg(-1) to 1500 mg kg(-1) under simultaneous exposure
      to UV radiation and visible light to determine concentration/response
      relationships. No significant mortality occurred with any treatment. Significant
      effects due to sealants included decreased righting ability and diminished liver
      enzyme activities. Coal-tar sealant was more effective in inducing these changes
      than was asphalt sealant.

PMID- 20696465
TI  - An evaluation of teeth of ringed seals (Phoca hispida) from Greenland as a matrix
      to monitor spatial and temporal trends of mercury and stable isotopes.
AB  - Total mercury (Hg) concentrations were measured in teeth of ringed seals from
      Qeqertarsuaq, central West Greenland (1982 to 2006) and Ittoqqortoormiit, central
      East Greenland (1986 to 2006). Stable isotopic ratios of carbon ((13)C/(12)C) and
      nitrogen ((15)N/(14)N) were determined as well to provide insights into diet
      variations between regions or through time. Mercury concentrations decreased the
      first years of life of the animals suggesting that Hg had been transferred from
      the mother to the foetus and newborn. The Hg concentrations in teeth were
      significantly lesser in ringed seals from central West Greenland compared to
      those from central East Greenland. Carbon and nitrogen stable isotopic values
      measured in the animals differed also significantly between the two regions.
      Increasing temporal trends of dental Hg concentrations between 1994 and 2006 were
      observed in ringed seals from both central West Greenland and central East
      Greenland. These increases were attributed to global changes in environmental Hg
      levels since no temporal trends in delta(15)N values were found to support the
      hypothesis of a diet shift over time. Furthermore, a decreasing temporal trend in
      delta(13)C values was observed in the teeth of seals from central East Greenland,
      and explained by a likely change over time towards more pelagic feeding habits;
      alternatively, the so-known Seuss effect was thought to be responsible for this
      decrease. Finally, it was concluded that the tooth of ringed seal was a good
      monitoring tissue to assess Hg trends.

PMID- 20696466
TI  - Municipal landfill leachates: a significant source for new and emerging
      pollutants.
AB  - Landfills have historically remained the most common methods of organized waste
      disposal and still remain so in many regions of the world. Thus, they may contain
      wastes resulting from several decades of disposal and decomposition with
      subsequent release of organic compounds that may have environmental, wildlife and
      human health consequences. Products containing different types of additives with
      unique beneficial improvement properties are in daily use. However, when these
      products are decomposed, additives are release into the environment, some of
      which have been shown to have negative environmental impacts, resulting in the
      ban or at least restricted application of some chemicals. New and emerging
      compounds are continuously discovered in the environment. Herein, we report
      qualitative and quantitative data on the occurrence of new and emerging compounds
      with increasing environmental and public health concern in water- and particle
      phase of landfill leachates. Under normal environmental conditions, several of
      these chemicals are persistent high-volume products. Identified chemicals in the
      leachates at nanogram (ng) or microgram (microg) per liter levels include -
      chlorinated alkylphosphates such as tris(1-chloro-2-propyl) phosphate (TCPP), N
      butyl benzensulfonamide (NBBS), the insect repellent diethyl toluamide (DEET) and
      personal care products such as the non-steroidal anti-inflammatory drug ibuprofen
      and polycyclic musk compounds. Among new and emerging contaminants,
      perfluorinated compounds (PFCs) were measured in the water phase at
      concentrations up to 6231 ng/L. Compared with the other chemicals, PFCs were
      primarily distributed in water phase. An effective removal method for PFCs and
      other polar and persistent compounds from landfill leachates has been a major
      challenge, since commonly used treatment technologies are based on aeration and
      sedimentation. Thus, the present study has shown that municipal landfill
      leachates may represent a significant source of concern for legacy, new and
      emerging chemicals in groundwater.

PMID- 20696467
TI  - Cellular origin of platelet-derived microparticles in vivo.
AB  - INTRODUCTION: Microparticles (MP), presumably of platelet origin, are the most
      abundant microparticles in blood. To which extent such MP may also directly
      originate from megakaryocytes, however, is unknown. During hematopoietic stem
      cell transplantation, patients undergo total body irradiation which leads to an
      irreversible destruction of hematopoiesis. MATERIAL AND METHODS: We studied the
      levels of "platelet-derived" MP (PMP) in 13 patients before and after total body
      irradiation with 12 Gy (4 Gy for 3 days, dose rate 4.5 cGy/min). PMP were
      isolated and double-stained with annexin V and anti-CD61. In 6 patients, we
      additionally analyzed MP exposing P-selectin or CD63. RESULTS: PMP rapidly
      declined upon total body irradiation, which was 2.4-fold faster than platelet
      disappearance. In contrast, the kinetics of MP exposing P-selectin or CD63 was
      comparable to platelets. CONCLUSIONS: Since CD61-positive MP disappear faster
      than platelets or MP exposing P-selectin or CD63, our data indicate that MP
      exposing P-selectin or CD63 are likely to originate from platelets, whereas at
      least a major fraction of CD61-exposing MP is likely to originate from
      megakaryocytes in vivo.

PMID- 20696468
TI  - An in vivo experimental study on osteopenia in diabetic rats.
AB  - Osteopenia is a significant problem associated with Diabetes mellitus. Osteopenia
      may result in an increased delay in healing of bone fractures and subsequently
      affect the quality of life. We evaluated the immunohistochemical localization of
      TRAIL and its receptor DR5 in the femoral bone of 10-week-old Sprague-Dawley male
      rats treated with sesame oil (control, group 1), streptozotocin (STZ), a diabetes
      inducer (group 2), L-NAME, a general inhibitor of NOS activity (group 3), L
      arginine (group 4), (arginine acts as a NO substrate) and iNOS immunostaining in
      group 1 and group 4. Histological and histochemical findings showed decreased
      growth of metaphyseal cartilage (which was thinner), decreased osteoid surface,
      and reduced mineral apposition rate in STZ- and L-NAME-treated rats. These
      findings confirm that bone formation is impaired in diabetic osteopenia. L
      arginine supplementation seems to prevent diabetes-induced bone alterations and
      preserve the calcification process, allowing synthesis of new bone matrix. The
      immunohistochemical study revealed increased immunostaining of TRAIL and DR5 in
      osteoblastic cells of the diaphysis (pre-metaphysis) and epiphysis treated with
      STZ and L-NAME, related to activation of osteoblastic apoptotic death, while the
      group receiving L-arginine was comparable to the control group and the higher
      indications of iNOS activity that may reflect its induction by L-arginine
      administration. The action of L-arginine suggests that increased NO synthesis and
      availability is potentially useful for effective prevention and treatment of
      diabetic osteopenia.

PMID- 20696469
TI  - Processing time shifts affects the execution of motor responses.
AB  - We explore whether time shifts in text comprehension are represented spatially.
      Participants read sentences involving past or future events and made sensibility
      judgment responses in one of two ways: (1) moving toward or away from their body
      and (2) pressing the toward or away buttons without moving. Previous work
      suggests that spatial compatibility effects should be observed, where the future
      is mapped onto responses away from the body, and the past is mapped onto
      responses toward the body. These effects were observed, but only when
      participants were moving to make their responses, and only for larger time shifts
      (e.g., a month).

PMID- 20696470
TI  - A stimuli-responsive hydrogel for doxorubicin delivery.
AB  - The goal of this study was to develop a polymeric carrier for delivery of anti
      tumor drugs and sustained release of these agents in order to optimize anti-tumor
      activity while minimizing systemic effects. We used oligo(poly(ethylene glycol)
      fumarate) (OPF) hydrogels modified with small negatively charged molecules,
      sodium methacrylate (SMA), for delivery of doxorubicin (DOX). SMA at different
      concentrations was incorporated into the OPF hydrogel with a photo-crosslinking
      method. The resulting hydrogels exhibited sensitivity to the pH and ionic
      strength of the surrounding environment. Our results revealed that DOX was bound
      to the negatively charged hydrogel through electrostatic interaction and was
      released in a timely fashion with an ion-exchange mechanism. Release kinetics of
      DOX was directly correlated to the concentration of SMA in the hydrogel
      formulations. Anti-tumor activity of the released DOX was assessed using a human
      osteosarcoma cell line. Our data revealed that DOX released from the modified,
      charged hydrogels remained biologically active and had the capability to kill
      cancer cells. In contrast, control groups of unmodified OPF hydrogels with or
      without DOX did not exhibit any cytotoxicity. This study demonstrates the
      feasibility of using SMA-modified OPF hydrogels as a potential carrier for
      chemotherapeutic drugs for cancer treatments.

PMID- 20696471
TI  - The biocompatibility of rapidly degrading polymeric stents in porcine carotid
      arteries.
AB  - The goal of this study was to evaluate the biocompatibility of materials for use
      in fully bioabsorbable vascular stents. 10:90 poly(L-lactic-co-glycolic acid)
      (10:90 L-PLGA), 85:15 poly(L-lactic-co-glycolic acid) (85:15 L-PLGA),
      polydioxanone (PDO), and poly-L-lactic acid (L-PLA) polymers were chosen as
      materials. Polymeric fibers were woven into a braided structure with a mass
      equivalent to or greater than that expected for a vascular stent, secured to
      balloon-expandable bare metal stents and implanted into porcine carotid arteries.
      The in vivo response was analyzed at 30 and 90 days by angiography,
      histopathology, and histomorphometry. All vessels were patent at 30 and 90 days.
      Injury score and neointima formation was mild for all samples. The faster
      degrading 10:90 L-PLGA had the highest inflammatory response at 30 days, but was
      completely absorbed with minimal inflammation and neointimal formation at 90
      days. PDO showed signs of partial absorption at 90 days, while 85:15 L-PLGA and L
      PLA demonstrated minimal absorption at 30 and 90 days. The inflammatory response
      to these three groups was similar over the experimental period. Using a robust
      materials-testing platform, we demonstrated long-term patency and intravascular
      biocompatibility of bioabsorbable polymers with varying rates of resorption. The
      data point to biocompatibility of a polymeric stent in the vascular space that is
      fully absorbable in less than a year.

PMID- 20696472
TI  - Heat-killed Lactobacillus rhamnosus GG modulates urocortin and cytokine release
      in primary trophoblast cells.
AB  - A number of studies are showing that probiotic treatment induces an anti
      inflammatory state. Intrauterine infection can lead to preterm delivery by
      modulating immune function and efforts to prevent this condition are ongoing
      nowadays. Lactobacillus rhamnosus GG (LGG) is a probiotic known to ameliorate
      inflammation by increasing local anti-inflammatory mediators in urinary and
      gastrointestinal tracts. The present study then analyzed the effect of heat
      killed LGG over beta-hCG, progesterone, interleukins (IL) 4 and 10, tumor
      necrosis factor-alpha (TNF-alpha), corticotropin releasing hormone (CRH) and
      urocortin (Ucn) release by primary trophoblast cells. Normal human term placentas
      (n = 6) were collected and purified trophoblast cells were incubated in the
      presence of LGG, lipopolysaccharide (LPS) or either LGG + LPS during 3 h, after
      which the target substances were quantified by ELISA and real-time PCR. LGG did
      not affect beta-hCG, progesterone, or CRH secretion. Conversely, LGG increased IL
      4 protein and mRNA expression (P < 0.05) while IL-10 and Ucn secretion were
      increased in a dose dependent manner and the highest dose of LGG increased
      significantly IL-10 mRNA (P < 0.05). LGG did not alter TNF-alpha, while LPS
      exposure increased TNF-alpha protein (P < 0.001) and mRNA expression (P < 0.01).
      Conversely, LGG treatment reversed LPS-induced TNF-alpha release at both protein
      (P < 0.01) and mRNA levels (P < 0.05) in a dose dependent fashion. In conclusion,
      LGG stimulates IL-4, IL-10 and Ucn expression and reverses LPS-induced TNF-alpha
      release from trophoblast cells, with no change in beta-hCG or progesterone
      release, suggesting that this probiotic may play a role as an immunomodulatory
      agent in human placenta without altering basic trophoblast functions.

PMID- 20696473
TI  - Clinical features and outcomes of 49 Turkish patients with acute promyelocytic
      leukemia who received ATRA and anthracyclines (PETHEMA protocol) therapy.

PMID- 20696474
TI  - Race and intensity of post-remission therapy in acute myeloid leukemia.
AB  - BACKGROUND: In many cancers, including AML, blacks have poorer overall survival.
      We investigated whether differences in post-remission therapy (PRT) were a
      contributing factor. METHODS: We compared PRT cycle number and intensity and time
      to PRT in blacks and whites, among 460 patients with newly diagnosed AML.
      RESULTS: Blacks and whites had PRT of equal cycle intensity and number, but black
      patients experienced a significant delay in starting PRT (2.73 months in blacks
      vs. 1 month in whites, p=0.047). Overall survival was equivalent in blacks and
      whites. CONCLUSION: PRT is delayed in blacks but does not explain differences in
      survival.

PMID- 20696475
TI  - Alterations in mRNA expression of acetylcholinesterase in brain and muscle of
      common carp exposed to atrazine and chlorpyrifos.
AB  - The uses of pesticides and herbicides have become an integral part of modern
      agricultural systems. The intensive use of pesticides chlorpyrifos (CPF) and
      herbicides atrazine (ATR) has resulted in serious environmental problems. Herein,
      we have developed real-time quantitative polymerase chain reaction assays for
      common carp (Cyprinus carpio L.) mRNA. The levels of AChE mRNA were evaluated in
      brain and muscle collected from common carp by treatment of ATR, CPF, and their
      mixture. The decreased transcription of AChE was detected in both tissues at
      different doses of the toxicants in the end of exposure tests, and the changes
      were improved in the end of recovery tests in varying degrees. It is suggested
      that transcription inhibition of AChE might be significant in long-playing single
      or associated exposure of ATR and CPF in common carp. Alteration in transcription
      of AChE caused by ATR, CPF, and their mixture could reveal the toxic mechanisms
      related to cholinergic signaling.

PMID- 20696476
TI  - Metal-specific effects on metallothionein gene induction and riboflavin content
      in coelomocytes of Allolobophora chlorotica.
AB  - Metal pollution affects earthworm coelomocytes, including their differential
      counts, riboflavin content and metallothioneins (MT) involved in metal
      homoeostasis and detoxification. The present work shows effects of Ni, Cu, Zn,
      Cd, and Pb at the same molarity (1mM) on coelomocytes of Allolobophora chlorotica
      after 2-day worm dermal exposure to metal chlorides. Numbers of
      coelomocytes/eleocytes extruded by electric shock and amounts of riboflavin in
      coelomocyte lysates were significantly decreased in Cu-exposed worms, less
      diminished in response to Ni, Zn, Cd, and unaffected by Pb. In sharp contrast,
      real-time PCR revealed a very strong (272 fold) MT-mRNA induction in response to
      Cd only. The induction was very low in response to Zn, Cu, Pb, and Ni ions (2.6,
      2.1, 1.4, and 1.3-fold, respectively). In conclusion, decreased cell counts and
      riboflavin content are molecular biomarkers of Cu exposure while induction of MT
      mRNA is a molecular biomarker of worm Cd exposure.

PMID- 20696477
TI  - Response of mung bean cultivars to fly ash: growth and yield.
AB  - Field experiments were conducted to evaluate the effect of fly ash on growth and
      yield of three locally grown cultivars of an important leguminous plant mung bean
      (Vigna radiata L.) on soil amended with different concentrations of fly ash. The
      values of pH, EC, WHC, soil cations, total heavy metals of the soil increased;
      however, values of BD, NH(4)(+)-N, NO(3)(-)-N, total N, organic carbon (OC),
      organic matter (OM), available P and cation exchange capacity (CEC) decreased
      with fly ash incorporation in the soil. Fly ash amendment led to improve the
      growth performance and various yield attributes. An increase in all the growth
      parameters was recorded in 10% fly ash amended (FAA) soil for cv M. Jyoti and M.
      Janpriya, while 5% FAA soil was most suitable for cv M. Jagriti. Yield (gm(-2))
      also increased significantly by 40.6% and 33.9% for cv M. Jyoti and M. Janpriya,
      respectively, in 10% FAA soil and by 29.5% in cv M. Jagriti in 5% FAA soil. The
      experimental results depict that different cultivars of mung bean demonstrate a
      marked difference in response to various concentrations of fly ash under field
      conditions and this may indicate a genetic base for variability.

PMID- 20696478
TI  - Evaluation of zebrafish DNA integrity after exposure to pharmacological agents
      present in aquatic environments.
AB  - Over the past few years, the increasing and uncontrolled use of pharmaceutical
      substances in agriculture, fish farming, human health and in veterinary medicine,
      together with an improper use of out-of-date medicines, has led to a consequent
      increase in the environmental problems linked to their disposal. In some Italian
      waste water treatment plants were found furosemide, a diuretic; ranitidine, an
      antiulcer drug; bezafibrate, a lipid regulator and ibuprofen, a painkiller. The
      present paper shows, by means of the synergic application of three tests (the
      Comet Test, the Diffusion Assay and the RAPD-PCR technique), how the DNA of
      zebrafish can be damaged after exposure to the above mentioned drugs. The data
      from the Comet Test, the Diffusion Assay and the RAPD-PCR technique were
      generally in agreement; these results show that all four drugs are genotoxic.

PMID- 20696479
TI  - Three studies on self-report scales to detect bipolar disorder.
AB  - BACKGROUND: This study investigated the usefulness of self-report scales for
      detecting bipolar disorder in several settings. METHODS: Study 1 developed a
      short form of the Hypomanic Personality Scale (the HPS-6) based on
      clinic/community and undergraduate samples. Study 2 used this scale for
      recruiting participants with bipolar disorder from the community. Study 3
      administered the full-length Hypomanic Personality Scale, the Mood Disorder
      Questionnaire, and a short form of the General Behavior Inventory (the GBI-15) to
      an undergraduate sample. Each study featured a reference standard diagnostic
      interview. RESULTS: In Study 2, about half of those responding to the
      advertisement (based on the HPS-6 developed in Study 1) reported a history of at
      least one hypomanic episode on a telephone-based SCID. In Study 3, the most
      robust findings emerged for the GBI-15: about one-third of participants screening
      positive on that measure met criteria for bipolar disorder using the Structured
      Clinical Interview for the DSM-IV (SCID). LIMITATIONS: Despite large sample sizes
      and stratified sampling, this study was limited by a low number of participants
      with bipolar I disorder. CONCLUSIONS: These three studies produced mixed findings
      regarding the detection of bipolar disorder via self-report. The HPS-6 was
      reasonably successful in recruiting participants with a history of at least one
      manic or hypomanic episode into a study on bipolar disorder. The GBI-15 showed
      some promise as a screening tool in an undergraduate setting, but there is a need
      for more sensitive and specific scales. Discussion focuses on potential
      strategies for developing such scales.

PMID- 20696480
TI  - Treatment and prevention of depression after surgery for hip fracture in older
      people: cost-effectiveness analysis.
AB  - OBJECTIVE: For older people who have had hip fracture surgery, to evaluate the
      cost-effectiveness of a nurse-led intervention in treating depression compared to
      treatment as usual (TAU), and to evaluate the cost-effectiveness of a
      psychological treatment for the prevention of depression. DESIGN: Two linked cost
      effectiveness studies for the treatment and prevention of depression after hip
      surgery, from the perspective of health, social care, voluntary sector agencies
      and unpaid carers. SETTING: Orthopaedic units in Manchester, England.
      PARTICIPANTS: One hundred and twenty-one patients with Geriatric Depression Scale
      (GDS) scores greater than 6 were included in the treatment study and 172 patients
      with GDS scores less than or equal to 6 were enrolled in the prevention study.
      INTERVENTIONS: Nurse-led intervention for treating depression versus TAU; and
      cognitive behaviour therapy (CBT) for preventing depression following surgery for
      hip fracture. MAIN OUTCOME MEASURES: Outcomes were changes in HADS-depression
      scores at 6 weeks. Costs covered treatment and all service impacts. RESULTS:
      After 6 weeks, there were no significant differences in cost. However, the nurse
      led intervention group had a lower mean HADS-depression score compared to TAU. In
      the prevention study, there were no significant differences in cost and
      depression score between patients treated with CBT and TAU. CONCLUSION: The
      results for this parallel randomized controlled study show that after hip
      fracture surgery a nurse-led intervention may be a cost-effective option for the
      treatment of depression in older people with depression. However CBT does not
      appear to be a cost-effective option for the prevention of depression in this
      population.

PMID- 20696481
TI  - Not as golden as standards should be: interpretation of the Hamilton Rating Scale
      for Depression.
AB  - BACKGROUND: The Hamilton Rating Scale for Depression (HRSD) is one of the most
      frequently used instruments in antidepressant trials. METHODS: We examined
      different recommendations for classification of subjects according to depression
      severity by the HRSD. RESULTS: Several differences between recommendations were
      identified leading to the conclusion that a consensus on interpretation is
      largely missing. LIMITATIONS: Brief narrative review. CONCLUSIONS: Widely
      accepted standards for the interpretation of scores on the HRSD are needed.

PMID- 20696482
TI  - Metacognition in schizophrenia: correlates and stability of deficits in theory of
      mind and self-reflectivity.
AB  - Research suggests that many with schizophrenia experience a range of deficits in
      metacognition including difficulties recognizing the emotions and intentions of
      others as well as reflecting upon and questioning their own thinking. Unclear,
      however, is the extent to which these deficits are stable over time, how closely
      related they are to one another and whether their associations with core aspects
      of the disorder such as disorganization symptoms are stable over time. To explore
      this issue, we administered three assessments of Theory of Mind (ToM), the Beck
      Cognitive Insight Scale (BCIS), and the Positive and Negative Syndrome Scale at
      baseline and 6 months to 36 participants with schizophrenia. Correlations
      revealed the ToM and BCIS scores were stable across the two test administrations
      and that the ToM tests were closely linked to each other but not to the BCIS.
      Poorer baseline performance on the ToM tests and the Self-Certainty scale of the
      BCIS were linked to greater cognitive symptoms at baseline and follow-up, while
      greater Self-Reflectivity on the BCIS was linked to greater levels of emotional
      distress at both baseline and 6-month follow-up. Results are consistent with
      assertions that deficits in metacognition are a stable feature of schizophrenia.

PMID- 20696483
TI  - Time dependent expression of cytokines in Mycobacterium bovis infected cattle
      lymph nodes.
AB  - Advancements in the current diagnostic and vaccination protocols employed against
      bovine tuberculosis rely heavily upon a sound knowledge of the bovine
      immunological response. Central to this is the importance of timing in the
      cellular immune profile and how this dynamic process evolves post-Mycobacterium
      bovis challenge. In the present study, we quantitatively analysed mRNA expression
      of interferon gamma (IFN-gamma), tumour necrosis factor alpha (TNF-alpha) and
      interleukins (IL) 4 and 10 within select thoracic lymph nodes of cattle infected
      with M. bovis for 5, 12 and 19 weeks as compared to non-infected bovine tissues.
      The M. bovis infected lymph nodes displayed significantly higher expression
      levels of IFN-gamma and TNF-alpha as compared to the non-infected lymph node
      tissues. This, in conjunction with undetectable levels of IL4, suggests a pro
      inflammatory cytokine response. However a significant increase was also detected
      in IL10 mRNA which is consistent with a described aspect of T(H)1 type T cells in
      Leishmania infection, a 'self-limiting' process in which cells produced both IFN
      gamma and IL10 with the aim of controlling the heightened immunopathological
      responses. This was further reflected when comparing the cytokine profiles of the
      individual lymph node types, as those displaying a higher IFN-gamma/IL10 ratio
      also had a greater level of gross pathology. This data highlights the important
      role of IL10 in the bovine response to M. bovis infection and supports its
      involvement as an immunological marker of disease progression.

PMID- 20696484
TI  - GAD antibodies associated neurological disorders: incidence and phenotype
      distribution among neurological inflammatory diseases.
AB  - We investigated the prevalence and the clinical association of high titer of
      antibodies against glutamic acid decarboxylase (hGADAb) among unselected patients
      with inflammatory/autoimmune disorders of the nervous system. By indirect
      immunofluorescence examination of samples from 1435 patients, we identified 7
      cases (0.48%) with hGADAb. Although stiff-person plus syndrome was the commonest
      clinical accompaniment, most of the patients presented with a combination of
      different symptoms, including psychiatric disturbances and intestinal motility
      disorders. Diagnosis delay and chronic evolution were common findings. In two
      cases persistently high values of hGADAb over the years were observed. The rarity
      and the phenotype heterogeneity of hGADAb clinical association should not
      discourage clinicians from antibody screening, at least in selected cases, as an
      early immunotherapy can change the otherwise chronic progression of this complex
      disorder spectrum.

PMID- 20696485
TI  - Craniofacial growth in children with nasal septum deviation: a cephalometric
      comparative study.
AB  - OBJECTIVE: Nasal-breathing impairment has been described as a possible
      determinant of maxillofacial development in children with adenoids/tonsils
      hypertrophy. However little is known about the possible influence of nasal septum
      deviation on craniofacial growth in childhood. We conducted a multicenter
      cephalometric study to compare skeletal and dental features in children with
      chronic nasal-breathing obstruction secondary to nasal septum deviation and nose
      breathing controls. METHODS: Ninety-eight children (59M, 39F; mean age 8.8 years;
      age range 7-12 years) with obligate mouth-breathing secondary to nasal septum
      deviation (group 1) and 98 age- and sex-matched nasal-breathing controls (group
      2) were evaluated. Nasal-breathing function was assessed in all patients with
      clinical history, ENT instrumental examination and anterior active
      rhinomanometry. Cephalometric parameters were recorded in all subjects. RESULTS:
      Patients of group 1 showed a statistically significant increase of upper anterior
      facial height (N-palatal plane) and total anterior facial height (N-Me) with
      regards to group 2. The angular relationships of the sella-nasion, palatal, and
      occlusal planes to the mandibular plane were greater in group 1 in comparison to
      controls. The gonial angle (Ar-Go-Me), palatal height and overjet were
      significantly higher in the mouth-breathing group. A significantly retrognatic
      position of the maxilla and mandible was recorded in group 1 in comparison to
      group 2. Most mouth-breathing children showed class II malocclusion, while the
      majority of control subjects presented normal occlusion. The prevalence of cross
      bite was higher in group 1 with respect to controls (p=0.02). CONCLUSION:
      Children with obligate mouth-breathing due to nasal septum deviations show facial
      and dental anomalies in comparison to nose-breathing controls. Possible
      physiologic explanations of our findings are reported.

PMID- 20696487
TI  - Stray dog population demographics in Jodhpur, India following a population
      control/rabies vaccination program.
AB  - Animal Birth Control (ABC) is a program by which stray dogs are sterilized and
      vaccinated against rabies with the aim of controlling both dog population size
      and rabies. Population size and demographics of stray dogs were measured before
      and after implementation of an ABC program in Jodhpur, India. Dog population size
      declined (p<0.05) in three of five areas surveyed, showed a decreasing trend
      (p>0.05) in 1 area, and remained stable in 1 area between 2005 and 2007. By 2007,
      61.8-86.5% of the free-roaming dog population was surgically sterilized and
      vaccinated for rabies in the areas surveyed. In March-May, 2007, adults comprised
      80-96% of the free-roaming dog population, while subadults and puppies comprised
      0-18 and 0-4%, respectively. The male:female ratio among dogs>3 months old was
      1.4:1. A population demographic model predicted that at the current level of
      sterilization/rabies vaccination, vaccination coverage would remain above 70%,
      and the dog population would decrease by 69% reaching stability after 13-18
      years. A surgical sterilization coverage under 40% would maintain the dog
      population at current levels.

PMID- 20696486
TI  - Management practices associated with the bulk-milk prevalence of Staphylococcus
      aureus in Canadian dairy farms.
AB  - When designing mastitis-prevention and control programs, it is important to know
      the level of adoption of mastitis-prevention management practices and control
      programs and the herd-level prevalence of contagious mastitis pathogens. Our
      objectives were to estimate: (1) adoption of recommended mastitis-preventive
      management on Canadian dairy farms; (2) herd-level prevalence of contagious
      mastitis pathogens on Canadian dairy farms; and (3) associations of certain
      management practices with the isolation of Staphylococcus aureus from the bulk
      tank milk from Canadian dairy farms. In total, 226 farms participating in dairy
      herd improvement milk recording were randomly selected. All participating farms
      in British Columbia had free-stall barns and 85% of farms in Quebec had tie-stall
      barns. Post-milking teat disinfection was practised on 96% of the farms and 72%
      had implemented blanket dry-cow treatment. Weighted and province-stratified
      prevalence of Streptococcus agalactiae and Staph. aureus in bulk tank milk was 4%
      (95% confidence interval: 0-12%) and 74% (95% confidence interval: 61-86%),
      respectively. Highest Staph. aureus prevalence was found in Nova Scotia (91%) and
      lowest prevalence in British Columbia (38%). No Mycoplasma spp. were isolated,
      but detection of Mycoplasma spp. could have been hampered by the frozen shipment
      and storage of the milk samples. Management practices associated with a lower
      probability of isolating Staph. aureus were blanket dry-cow treatment and
      believing that a nutritionist is important in mastitis data review. Having the
      milking equipment checked by an independent technician at least once a year and
      rubber mats or mattresses in the free-stall barns were associated with an
      increased probability of isolating Staph. aureus from the bulk tank. Most of
      Canadian dairy farms adopted important mastitis-prevention practices, such as
      post-milking teat disinfection and drying off all cows with antibiotics; however,
      improvements can still be made. A few management practices were associated with
      the prevalence of Staph. aureus in bulk tank milk, such as dry-cow treatment and
      barn type for the lactating cows. Further work has to be carried out to
      investigate to what extent the associations are causal.

PMID- 20696488
TI  - A real-time PCR assay for detection and quantification of 2-branched (1,3)-beta-D
      glucan producing lactic acid bacteria in cider.
AB  - Ropiness in natural cider is a relatively frequent alteration, mainly found after
      bottling, leading to consumer rejection. It is derived from the production of
      exopolysaccharides (EPS) by some lactic acid bacteria most of which synthesize a
      2-branched (1,3)-beta-D-glucan and belong to the genera Pediococcus,
      Lactobacillus and Oenococcus. This polysaccharide synthesis is controlled by a
      single transmembrane glycosyltransferase (GTF). In this work, a method based on
      quantitative PCR (qPCR) and targeting the gtf gene was developed for detection
      and quantification of these bacteria in cider. The newly designed primers
      GTF3/GTF4 delimit a 151bp fragment within the 417bp amplicon previously designed
      for conventional PCR. The inclusivity and exclusivity of the qPCR assay were
      assessed with 33 cider isolates belonging to genus Lactobacillus, Oenoccocus and
      Pedioccocus, together with reference strains of 16 species and five genera
      including beta-glucan, alpha-glucan and heteropolysaccharide (HePS) producing
      strains and non-EPS producers. The qPCR assay, followed by the melting curve
      analysis, confirmed the generation of a single PCR product from the beta-glucan
      producers with a T(m) of 74.28+/-0.08 and C(T) values (10ng DNA) ranging between
      8.46 and 16.88 (average 12.67+/-3.5). Some EPS(-) LAB strains rendered C(T)
      values ranging from 28.04 to 37.75 but they were significantly higher
      (P(C(T)<28.54)=0.05) than those of the beta-glucan producers. The assay showed a
      wide quantification range of 5 log units using calibrated cell suspensions of
      Pediococcus parvulus 2.6 and Oenococcus oeni I4. The linearity was extended over
      7 log orders when calibration curves were obtained from DNA. The detection limit
      for beta-glucan producing LAB in artificially contaminated cider was about
      3x10(2)CFU per ml. The newly developed qPCR assay was successfully applied to
      monitor the cidermaking process, in 13 tanks from two cider factories, revealing
      a decrease in C(T) values derived from an increase in beta-glucan producing LAB
      populations. In addition, 8 naturally spoiled bottled cider were tested for the
      quantification of these organisms using the five standard curves constructed: P.
      parvulus 2.6 genomic DNA and gtf amplicon (417bp), calibrated cell suspensions of
      Pediococcus parvulus 2.6, Lactobacillus diolivorans G77 and Oenococcus oeni I4
      and results were compared to LAB total counts on MRS. Levels obtained from the
      different approaches were within a log range and showed no significant
      differences. Therefore, the amplicon-derived standard curve is proposed for the
      routine estimation of gtf(+)populations in cider.

PMID- 20696489
TI  - Bacterial species associated with traditional starter cultures used for fermented
      bamboo shoot production in Manipur state of India.
AB  - Soidon is a non-salted acidic fermented food prepared from the succulent bamboo
      shoot tip of Schizostachyum capitatum Munro by using a traditional liquid starter
      called "soidon mahi" in Manipur state of India. In this study, 163 bacterial
      isolates associated with this starter samples were identified and their
      population distribution was investigated by amplified ribosomal DNA restriction
      analysis (ARDRA), 16S rDNA sequencing and randomly amplified polymorphic DNA
      (RAPD) analysis. This acidic starter (pH 4.5+/-0.15) was dominated by a
      characteristic association of Bacillus and lactic acid bacteria (LAB) together.
      The population distribution of dominant species were Bacillus subtilis 29.3%,
      Bacillus cereus 35.7%, Bacillus pumilus 2.6%, Lactobacillus brevis 9.6%,
      Lactobacillus plantarum 5.1%, Carnobacterium sp. 11.9%, Enterococcus faecium 1.2%
      and Pseudomonas fluorescens 4.6%. Alarming population load (10(6)-10(7)cfu/ml) of
      B. cereus in 87% of starter samples studied should raise concern regarding
      biosafety of soidon consumption. PCR amplification of 16S-23S rDNA intergenic
      transcribed spacer (ITS) region and ITS-RFLP profiles revealed a high diversity
      with eight subgroups in B. subtilis, five subgroups in B. cereus and three
      subgroups in L. brevis isolates. The most abundant B. subtilis subgroup IB.1
      distributed in most of the samples showed very less clonal variability during
      RAPD analysis. The molecular methods used in this study identified the dominant
      strains of Bacillus and LAB distributed in most of the starter samples. These
      dominant strains of B. subtilis, L. brevis and L. plantarum would allow for
      developing a defined starter culture for the production of quality soidon.

PMID- 20696490
TI  - Postharvest management of gray mold and brown rot on surfaces of peaches and
      grapes using electrolyzed oxidizing water.
AB  - This study evaluated the potential use of near-neutral (pH=6.3-6.5) electrolyzed
      oxidizing water (EO water) to inactivate pure cultures of Botrytis cinerea and
      Monilinia fructicola and to mitigate fungal infection of these organisms on fruit
      surfaces. Treatment of these organisms, in pure culture, with EO water at
      concentrations of 25, 50, 75, and 100ppm total residual chlorine (TRC) and 10 min
      of contact time resulted in a 6 log(10) spores/mL reduction of both organisms. A
      dip treatment or a dip and daily spray treatment of EO water were used to
      evaluate its ability to prevent or delay the onset of surface infection on fruit
      during postharvest packaging and in retail shelf environments. A 10 minute dip
      treatment of surface inoculated peaches (M. fructicola) in EO water prevented
      infection for 3 days and resulted in a 12.5% incidence of infection and a disease
      severity rating of 6% after 5 days of storage at 25 degrees C. Dipping of green
      table grapes inoculated with B. cinerea into EO water prevented infection for 7
      days and resulted in a 1% incidence of infection and a disease severity rating of
      2% after 10 days of storage at 25 degrees C. A dip and daily spray of peaches
      with EO water prevented infection for 12 days and resulted in a 10% incidence of
      infection and a 6% disease severity after 14 days of storage at 25 degrees C. A
      dip and daily spray of grapes with EO water prevented infection for 24 days and
      resulted in a 2% incidence of infection and a disease severity rating of 2% after
      26 days of storage at 25 degrees C. The results from this study suggest that
      these solutions may prove to be effective for postharvest sanitation of fruit
      surfaces prior to packaging and may increase the shelf life of the fruit in
      commercial settings.

PMID- 20696491
TI  - Influence of NaCl reduction and replacement on the growth of Lactobacillus sakei
      in broth, cooked ham and white sauce.
AB  - The growth inhibiting effects of NaCl and selected simple salt replacers
      (CaCl(2), MgCl(2), KCl and MgSO(4)) on the growth of Lactobacillus sakei were
      studied in de Man Rogosa Sharpe broth at 7 degrees C over a water phase
      concentration of 0 to 6.4%. The divalent chloride salts (CaCl(2) in particular)
      generally had the largest antimicrobial activities at equivalent water phase
      concentrations, molalities or water activity (a(w)) values. MgSO(4) had not only
      the least antimicrobial activity but also the smallest a(w) depressing capacity.
      The results also showed that the antimicrobial effects of CaCl(2) were not fully
      accounted for by its a(w) depressing effects. Challenge tests performed on cooked
      ham and white sauce showed that reduction of NaCl levels by 28 and 33%,
      respectively, had no influence on the microbial stability of these products to L.
      sakei. Ultimately the study concluded that the microbiological consequences of
      the full or partial replacement of NaCl on the growth of L. sakei largely depend
      on the initial level of NaCl, the level of replacement and the nature of the salt
      replacer used. Altered stability to L. sakei is most likely given a high initial
      NaCl level, combined with a large level of partial replacement with either
      CaCl(2) (increased stability) or MgSO(4) (reduced stability) as the replacer.

PMID- 20696492
TI  - Mimivirus: the emerging paradox of quasi-autonomous viruses.
AB  - What is a virus? Are viruses alive? Should they be classified among
      microorganisms? One would expect these simple questions to have been settled a
      century after the discovery of the first viral disease. For years, modern
      virology successfully unravelled the huge diversity of viruses in terms of
      genetic material, replication mechanism, pathogenicity, host infection, and more
      recently particle structure, planet-wide distribution and ecological
      significance. Yet, little progress was made in understanding their evolutionary
      origin(s), as well as the fundamental nature of their relationship with the
      cellular world. Thanks to the recent studies on Mimivirus and other large DNA
      viruses, we are now entering a new era where the most basic concepts about
      viruses are revisited, including their true nature, how fundamentally different
      they are from cellular microorganisms, and how essential they might have been in
      the major innovations that punctuated the evolution of life.

PMID- 20696493
TI  - Multiple ferredoxin isoforms in Chlamydomonas reinhardtii - their role under
      stress conditions and biotechnological implications.
AB  - The unicellular green alga Chlamydomonas reinhardtii has at least six plant-type
      ferredoxins (FDX). Besides the long-known photosynthetic ferredoxin PetF the
      isoforms Fdx2-Fdx6 have been identified. The FDX genes are differentially
      expressed under various environmental conditions such as the availability of
      oxygen, copper, iron and ammonium. Recently, the anaerobically induced Fdx5 as
      well as Fdx2, which is involved in nitrite reduction were characterized in more
      detail. Moreover, it was shown that PetF, the central and most abundant FDX of C.
      reinhardtii, is a suitable partner of the hydrogenase HydA1. Using mutant
      variants of both PetF and HydA1, amino acid residues essential for the
      interaction of both proteins could be identified. These findings will help to
      tailor PetF for achieving an optimized photobiotechnological hydrogen production
      in C. reinhardtii, which might also benefit from new insights into the mechanism
      of how oxygen attacks the active site metal cluster of HydA1. This review gives
      an update on recent advances in understanding the function of ferredoxins and the
      hydrogenase in C. reinhardtii.

PMID- 20696494
TI  - Different responses of tonoplast proton pumps in cucumber roots to cadmium and
      copper.
AB  - Cadmium (Cd) and copper (Cu) effects on the two tonoplast proton pumps were
      compared in cucumber roots. Different alterations of vacuolar H+ transporting
      ATPase (V-ATPase) (EC 3.6.3.14) and vacuolar H+ transporting pyrophosphatase (V
      PPase) (EC 3.6.1.1) activities under heavy metal stress were investigated. ATP
      dependent proton transport and ATP hydrolysis increased after exposure of
      seedlings to Cu, whereas both decreased in plants stressed with Cd. PP(i)
      hydrolysis was relatively insensitive to both heavy metals. However, cadmium, but
      not copper, clearly inhibited PP(i)-driven H+ transport. Changes in enzyme
      activities were not due to the metal action on the expression of CsVHA-A, CsVHA-c
      and CsVP genes encoding V-ATPase subunit A and c, and V-PPase, respectively, in
      cucumber roots. Moreover, immunoblot analysis using specific antibodies against V
      ATPase holoenzyme, phosphoserine and phosphothreonine suggested that the
      phosphorylation at Ser residue in regulatory subunit B of cucumber V-ATPase was
      not regulated by metals. Oxidative alterations of membrane lipids were measured
      as malondialdehyde (MDA) content. Cu ions, in contrast to Cd, visibly enhanced
      the lipid peroxidation in the root tonoplast fractions. Because ATP and PP(i) are
      absolutely required by V-ATPase and V-PPase, respectively, for proton transport,
      their contents were determined in the control roots and roots treated with
      cadmium and copper. Both ATP and pyrophosphate amounts decreased under heavy
      metal stress.

PMID- 20696497
TI  - [Is the permanent pacemaker implant more efficient in level 1 hospital?].
AB  - OBJECTIVE: To determine if permanent pacemaker implants (PPM) interventions and
      change of generator are more efficient in small hospitals. DESIGN: A cost
      effective analysis and retrospective, cross-sectional and observational study of
      diagnostic related groups (DRG). SETTING: The data was obtained from the national
      Minimum Basic Data Set (MBDS) for the year 2007 provided by the Health Ministry.
      PATIENTS: This includes the total number of patients who required treatment in
      all national hospitals for 5 DRG: 115 - bradyarrhythmic complication during the
      acute coronary syndrome, heart failure or shock; 116 -symptomatic isolated
      conduction defects; 117 -revisions, but without changing the battery, 118-
      application of a new one, 549 - implementation or revision but with serious
      complications. PRINCIPAL VARIABLES OF INTEREST: demographic, clinical (number of
      secondary diagnoses (NSD) and procedures (NP), mortality) and management (total
      and preoperative length of stay (LOS), access, discharge, hospital size),
      defining inefficient stays as those exceeding 2 days on the average. RESULTS:
      23,154 episodes, 5.3% small hospitals. The comparative bivariate study between
      small hospitals and the rest, not discriminated by DRG, showed a mean LOS of
      7.87+/-8.78 days vs 11.01+/-12.95 (p=0.005, 95% CI for mean difference [0.17,
      1.65]) and also lower than preoperatively (3.62+/-6.14 vs. 4.22+/-6.68 days
      (p=0.015)) without greater comorbidity, as measured by proxy through the NSD
      (5.23+/-2.88 vs 5.42+/-3.28 (p=0.055)) and NP as proxy of diagnostic and
      therapeutic effort (3.79+/-2.50 vs 3.55+/-2.69 (p=0.002)). A total of 24.1% were
      inefficient, there being an association with preoperative stay, NDS, NP and
      emergency access. CONCLUSION: Pacemaker implantation and generator change in
      small hospitals is more efficient, with internal consistency by subgroups.

PMID- 20696498
TI  - [Delirium risk assessment in elderly hospitalized patients].
AB  - Delirium is a major geriatric syndrome that affects a significant percentage of
      elderly hospitalized patients. It involves major negative consequences for users
      and professionals and can be prevented. The aim of this paper is to identify and
      describe the tools for predicting delirium in hospitalized patients. Lastly, the
      work analyzes the sources of heterogeneity and the scarcity of such instruments,
      as well as the reasons why their use is not widespread in clinical practice.

PMID- 20696495
TI  - Ibuprofen attenuates oxidative damage through NOX2 inhibition in Alzheimer's
      disease.
AB  - Considerable evidence points to important roles for inflammation in Alzheimer's
      disease (AD) pathophysiology. Epidemiological studies have suggested that long
      term nonsteroidal anti-inflammatory drug (NSAID) therapy reduces the risk for
      Alzheimer's disease; however, the mechanism remains unknown. We report that a 9
      month treatment of aged R1.40 mice resulted in 90% decrease in plaque burden and
      a similar reduction in microglial activation. Ibuprofen treatment reduced levels
      of lipid peroxidation, tyrosine nitration, and protein oxidation, demonstrating a
      dramatic effect on oxidative damage in vivo. Fibrillar beta-amyloid (Abeta)
      stimulation has previously been demonstrated to induce the assembly and
      activation of the microglial nicotinamide adenine dinucleotide phosphate (NADPH)
      oxidase leading to superoxide production through a tyrosine kinase-based
      signaling cascade. Ibuprofen treatment of microglia or monocytes with racemic or
      S-ibuprofen inhibited Abeta-stimulated Vav tyrosine phosphorylation, NADPH
      oxidase assembly, and superoxide production. Interestingly, Abeta-stimulated Vav
      phosphorylation was not inhibited by COX inhibitors. These findings suggest that
      ibuprofen acts independently of cyclooxygenase COX inhibition to disrupt
      signaling cascades leading to microglial NADPH oxidase (NOX2) activation,
      preventing oxidative damage and enhancing plaque clearance in the brain.

PMID- 20696496
TI  - Impact of changed positive and negative task-related brain activity on word
      retrieval in aging.
AB  - Previous functional imaging studies that compared activity patterns in older and
      younger adults during nonlinguistic tasks found evidence for 2 phenomena: older
      participants usually show more pronounced task-related positive activity in the
      brain hemisphere that is not dominant for the task and less pronounced negative
      task-related activity in temporo-parietal and midline brain regions. The combined
      effects of these phenomena and the impact on word retrieval, however, have not
      yet been assessed. We used functional magnetic resonance imaging to explore task
      related positive (active task > baseline) and negative activity (baseline >
      active task) during semantic and phonemic verbal fluency tasks. Increased right
      frontal positive activity during the semantic task and reduced negative activity
      in the right hemisphere during both tasks was associated with reduced performance
      in older subjects. No substantial relationship between changes in positive and
      negative activity was observed in the older participants, pointing toward 2
      partially independent but potentially co-occurring processes. Underlying causes
      of the observed functional network inefficiency during word retrieval in older
      adults need to be determined in the future.

PMID- 20696500
TI  - Schiff bases of indoline-2,3-dione (isatin) derivatives and nalidixic acid
      carbohydrazide, synthesis, antitubercular activity and pharmacophoric model
      building.
AB  - Tuberculosis (TB) remains among the world's great public health challenges.
      Worldwide resurgence of TB is due to two major problems: the AIDS epidemic, which
      started in the mid-1980s, and the outbreak of multidrug resistant (MDR) TB. Thus,
      there is an urgent need for anti-TB drugs with enhanced activity against MDR
      strains. In recent years, Schiff bases of 1H-indole-2,3-diones are reported to
      exhibit anti-TB activity. On the other hand, several quinolone antibacterial
      agents have been examined as inhibitors of TB, as well as other mycobacterial
      infections. Accordingly, the current work involved design and synthesis of Schiff
      bases of nalidixic acid carbohydrazide and isatin derivatives (5,6a-f and 7,8a
      c). Structures of the synthesized derivatives were confirmed on the bases of
      spectral methods of analyses. Anti-TB activity of the synthesized derivatives was
      investigated against four Mycobacterium strains: Mycobacterium intercellulari,
      Mycobacterium xenopi, Mycobacterium cheleneo and Mycobacterium smegmatis. Modest
      anti-TB activity was observed within the investigated compounds, however,
      compound 5f revealed potent anti-TB activity with MIC 0.625 microg/ml, which is
      20 times greater than the reference drug isoniazid, INH, (MIC = 12.5 microg/ml).
      A hypothetical pharmacophore model was built using Molecular Operating
      Environment (MOE) program and 10 compounds structurally related to the
      synthesized ones with reported anti-TB activity. The Pharmacophoric model built
      revealed the necessity of the following pharmacophoric features for anti-TB
      activity: aromatic center, hydrogen bond acceptor/metal ligator center, hydrogen
      bond donor center and aromatic center/hydrophobic area. Theses features were
      consistent with the found anti-TB activity of the tested compounds.

PMID- 20696501
TI  - Synthesis, characterization, antiamoebic activity and cytotoxicity of novel
      series of pyrazoline derivatives bearing quinoline tail.
AB  - The cyclization of chalcones (1a-1j) with 2-(quinolin-8-yloxy) acetohydrazide (2)
      under basic condition led to the formation of new compounds, pyrazoline
      derivatives (3a-3j). In vitro antiamoebic activity was performed against HM1:
      IMSS strain of Entamoeba histolytica. The results showed that the compounds 3d,
      3g, 3h, and 3j exhibited promising antiamoebic activity (IC(50) = 0.05 microM,
      0.31 microM, 0.06 microM, 0.29 microM) respectively than the standard drug
      metronidazole (IC(50) = 1.84 microM). The toxicological studies of these
      compounds on human breast cancer MCF-7 cell line showed that all the compounds
      3d, 3g, 3h, 3j and metronidazole were nontoxic at the concentration range of 1.56
      50 microM.

PMID- 20696502
TI  - Multivariate QSAR study on the antimutagenic activity of flavonoids against 3-NFA
      on Salmonella typhimurium TA98.
AB  - A quantitative structure-activity relationship (QSAR) study of twenty flavonoid
      derivatives with antimutagenic activity against 3-nitrofluoranthene (3-NFA) was
      performed by Partial Least Squares (PLS), using Ordered Predictors Selection
      (OPS) algorithm for variable selection. Four descriptors (PJI2, Mor27m, G1e and
      R4u+) were selected and a good model (n = 19; R(2) = 0.747; SEC = 0.332;
      PRESS(cal) = 1.768; F((2,27)) = 23.585; Q(LOO)(2) = 0.590; SEV = 0.388;
      PRESS(val) = 2.858; R(pred)(2) = 0.591; SEP = 0.394; ARE(pred) = 5.230%; k =
      1.005; k' = 0.990; |R(02) - R'(02)| = 0.109) was built with two latent variables
      describing 83.410% of the original information. Leave-N-out cross validation
      (LNO) and y-randomization were performed in order to confirm the robustness of
      the model. The topological descriptors selected indicate that the antimutagenic
      activity against 3-NFA depends on molecular size, shape and Sanderson
      electronegativity of flavonoids. The proposed model may provide a better
      understanding of the antimutagenic activity of flavonoids and can be used as a
      guidance for proposition of new chemopreventive agents.

PMID- 20696503
TI  - Development of isoniazid-NAD truncated adducts embedding a lipophilic fragment as
      potential bi-substrate InhA inhibitors and antimycobacterial agents.
AB  - Isoniazid-NAD truncated adducts embedding a lipophilic fragment were designed,
      synthesized and evaluated as inhibitors of the enoyl-acyl carrier protein (ACP)
      reductase (InhA) of Mycobacterium tuberculosis and as antimycobacterial agents.
      These compounds, planned as bi-substrate inhibitors and inspired from the active
      metabolite of isoniazid, combine both the nicotinamide moiety of the cofactor NAD
      and a lipophilic hydrocarbon chain mimic of the InhA substrate. The lipophilic
      fragment was introduced using either Suzuki-Miyaura cross-coupling or a classical
      nucleophilic substitution reaction. Several compounds developed in this work were
      indeed able to inhibit the InhA activity and showed promising antimycobacterial
      activities. However a direct correlation between the expressed activity and the
      bi-substrate mode of action could not yet be unambiguously demonstrated.

PMID- 20696504
TI  - Factors affecting assertiveness among student nurses.
AB  - This study aimed to investigate the factors affecting assertiveness among student
      nurses. The study was carried out at Faculty of Nursing, Port-Said University, on
      207 student nurses from four different grades. Rathus Assertiveness Schedule,
      consisted of 30 items, was used to measure the students' assertiveness level and
      a 12-item scale developed by Spreitzer was used to measure students'
      psychological empowerment. The study results showed that 60.4% of the students
      were assertive, while about half of the students were empowered. A positive
      relation between student assertiveness and psychological empowerment was
      detected. Moreover, positive relations regarding family income and students'
      assertiveness and psychological empowerment were determined. The study
      recommended introduction of specific courses aiming at enhancing the acquisition
      of assertiveness skills, in addition, nurse educators must motivate their
      students to express their opinion and personal rights and also they must pay
      attention for students' empowerment and enhance students' autonomy.

PMID- 20696505
TI  - Empowerment and being valued: a phenomenological study of nursing students'
      experiences of clinical practice.
AB  - AIM: The aim of the study was to explore the empowerment of nursing students in
      clinical practice. This paper focuses on 'being valued' as an important element
      of empowerment. BACKGROUND: Empowerment of nursing students is necessary in order
      for them to foster a sense of control and self-efficacy for those in their care.
      However, there is very little research on how to empower nursing students.
      Moreover, there is limited literature that specifically addresses the importance
      of students being valued in clinical practice. METHODS: Thirteen, first-year
      nursing students were recruited using purposive sampling. Data were generated
      through the means of in-depth, semi-structured interviews. Hermeneutic
      phenomenology was chosen as the underpinning philosophical approach because of
      its emphasis on actual experiences. FINDINGS: Being valued as a learner, being
      valued as a team member and being valued as a person are important factors in the
      empowerment of nursing students in clinical practice. These invariant themes are
      evident either implicitly or explicitly in the experiences of most students.
      DISCUSSION: When nursing students are valued as learners, team members and
      people, they feel empowered. Too often however, they experience disempowerment as
      a result of feeling devalued. This has a detrimental impact on their learning and
      intention to continue on the programme. According to the accounts of many nursing
      students effective mentorship and a supportive environment are factors that
      influence empowerment significantly. CONCLUSIONS: Strategies to promote the
      empowerment of nursing students in clinical practice need to address their sense
      of value.

PMID- 20696506
TI  - Supporting patient safety: examining communication within delivery suite teams
      through contrasting approaches to research observation.
AB  - OBJECTIVE: to explore the nature of intra- and interprofessional communication on
      delivery suites, with a particular focus on patient safety. DESIGN: longitudinal
      study using contrasting forms of observation: ethnographic methods alongside the
      highly structured Interaction Process Analysis (IPA) framework. SETTING: four
      contrasting delivery suites offering different models of care and serving
      different populations: two in the north of England and two in London.
      PARTICIPANTS: the multidisciplinary delivery suite teams and visiting
      professionals from related areas. KEY FINDINGS: the ethnographic observations and
      quantitative findings combine to highlight four principal areas relating to
      communication: communication underpinning collaboration; effects of workload
      pressures on communication practices; interprofessional communication; and the
      influence of architecture on communication. Contextual factors (e.g. case acuity,
      client throughput, model of care) underscore some inter site differences and
      attention is drawn to implications for safety. CONCLUSIONS AND IMPLICATIONS FOR
      PRACTICE: the use of complementary methods aided exploration of communication in
      the complex environment of the delivery suite. The findings reflect the
      complexity of communication patterns and the multiple influences on patterns and
      norms. Interprofessional tensions, workload pressures and the design of the
      environment can restrict communication, with implications for safety. As such,
      these findings have implications for policy in that safety solutions which focus
      efforts on standardising communication need to be located within wider strategies
      that also address structural and organisational networks and influences.

PMID- 20696507
TI  - In vivo 3D kinematics of normal forearms: analysis of dynamic forearm rotation.
AB  - BACKGROUND: Forearm rotation is an indispensable activity of daily living and
      comprises complex motions with rotational and translational components. It is
      thought that changes in these motions with injury or disease may affect
      diagnostic indices. Several studies have assessed in vivo forearm kinematics with
      static conditions, but dynamic forearm kinematics have not yet been reported. The
      purpose of this study was to analyze forearm kinematics during dynamic rotation
      using radiographic 3D-2D registration methods. METHODS: Ten forearms of five
      healthy males with the mean age of 37 years old were enrolled. Lateral
      fluoroscopic images were taken during forearm rotation from maximum supination to
      maximum pronation with their elbows flexed to approximately 45 degrees .
      Geometric bone models were created from CT scans of the humerus, the radius and
      the ulna. Three-dimensional kinematics were determined using 3D-2D model
      registration techniques with the images and models, and the arc of axial rotation
      of the radius, volar/dorsal translation of the ulna at the distal radioulnar
      joint and rotation axis of forearm were computed. FINDINGS: The radial rotation
      arc was 157 degrees . The ulna translated 3.9 mm (SD 1.5mm) dorsally during
      activity. The rotation axis of the forearm passed through the center of the
      radial head and the ulnar head at the 1.9 mm (SD 0.7 mm) posterior from its
      geometric centroid. INTERPRETATION: The posteriorly deviated rotation axis at the
      ulnar head may result in the ulnar head translating dorsally during pronation.
      These data provide a basis for objective assessment of pathological forearm
      function.

PMID- 20696508
TI  - Anatomical plate configuration affects mechanical performance in distal humerus
      fractures.
AB  - BACKGROUND: Because of strong loads acting in the elbow joint, intraarticular
      fractures with a methaphyseal comminuted fracture site at the distal humerus
      demand a lot from the osteosynthetic care. Ambiguities arise concerning to the
      anatomic position of the implants and the resulting mechanic performance. The aim
      of this biomechanical study was to compare the performance of different
      anatomical plate configurations for fixation of comminuted distal humerus
      fractures within one system. METHODS: In an artificial bone model two
      perpendicular and one parallel plating configuration of a dedicated elbow plating
      system were compared with respect to system rigidity (flexion and extension) and
      dynamic median fatigue limit (extension). The flexion tests were conducted under
      75 degrees  and the extension tests under 5 degrees . Furthermore, the relative
      displacements were recorded. As a fracture model an AO C 2.3-fracture on an
      artificial bone (4th Gen. Sawbone) was simulated via double osteotomy in sagittal
      and transversal plane. FINDINGS: Large differences in mechanical performance were
      observed between flexion and extension loading modes. In extension the parallel
      configuration with lateral and medial plates achieved the highest bending
      stiffness and median fatigue limit. In flexion the highest bending stiffness was
      reached by the construct with a medial and a postero-lateral plate. Failure of
      the implant system predominantly occurred at the screw-bone interface or by
      fatigue of the plate around the screw holes. INTERPRETATION: All three plate
      configurations provided sufficient mechanical stability to allow early
      postoperative rehabilitation with a reduced loading protocol. Although the
      individual fracture pattern determines the choice of plate configuration, the
      parallel configuration with lateral and medial plates revealed biomechanical
      advantages in extension only.

PMID- 20696509
TI  - A retrospective analysis of balance control parameters in elderly fallers and non
      fallers.
AB  - BACKGROUND: A cross-sectional retrospective study of parameters reflecting
      balance function in elderly fallers and non-fallers was conducted to better
      understand postural control mechanisms in individuals prone to falls. METHODS:
      Ninety-nine old adults (65-91 years, mean age 78.4 (SD 5.7)) from two self-care
      residential facilities participated in the study. Foot center-of-pressure (CoP)
      displacement data were collected during narrow base upright stance eyes closed
      conditions and analyzed using summary statistics and Stabilogram-Diffusion
      Analysis (SDA) for mediolateral (ML) and anteroposterior (AP) directions.
      Subjects were instructed to minimize body sway. FINDINGS: Twenty-nine of the
      subjects reported at least one fall and 69 subjects reported no falls in the past
      six months. The SDA showed significantly higher short-term diffusion coefficients
      and critical displacements in fallers in the ML but not the AP direction. Mean
      sway area and ML-CoP sway range were also larger in fallers. INTERPRETATION: The
      greater ML critical displacement seen in fallers suggests that balance
      corrections on average occurred at higher sway amplitudes in this population.
      This is consistent with an ML decrease in the sensitivity of their postural
      control system. A higher short-term diffusion coefficient is consistent with
      increased muscle stiffness, a possible compensation for lost control sensitivity.
      Testing balance function under narrow stance conditions provides a modest
      increase in task difficulty that may help reveal pre-conditions of the balance
      control system that could increase the risk of falls.

PMID- 20696510
TI  - Modeling the chemical and toxic water status of the Scheldt basin (Belgium),
      using aquatic invertebrate assemblages and an advanced modeling method.
AB  - Self-Organizing Maps have been used on monitoring sites in several Scheldt sub
      basins to identify the main aquatic invertebrate assemblages and relate them to
      the physico-chemical and toxic water status. 12 physico-chemical variables and 2
      estimates of toxic risk were available for a dataset made up of a total of 489
      records. Two of the five defining clusters reflecting a relatively clean
      environment were composed by very well diversified functional feeding groups and
      sensitive taxa. The cleanest assemblage was mainly linked to the sites from the
      Nete sub-basin. The three other clusters were inversely described with a
      dominance of oligochaetes and deposit feeders as well as a bad water quality.
      Such an analysis can be used to support ecological status assessment of rivers
      and thus might be useful for decision-makers in the evaluation of chemical and
      toxic water status, as required by the EU Water Framework Directive.

PMID- 20696511
TI  - Transport and degradation of pesticides in a biopurification system under
      variable flux Part II: A macrocosm study.
AB  - Transport of bentazone, isoproturon, linuron, metamitron and metalaxyl were
      studied under three different flows in macrocosms. The aim was to verify the
      observations from Part I of the accompanying paper, with an increase in column
      volume and decrease in chemical and hydraulic load. Very limited breakthrough
      occurred in the macrocosms for all pesticides, except bentazone, at all flows.
      From batch degradation experiments, it was observed that the lag time of
      metamitron and linuron decreased drastically in time for all flows, indicating a
      growth in the pesticide degrading population. This in contrast to isoproturon and
      metalaxyl, where an increase in lag time could be observed in time for all flows.
      From the batch degradation experiments, it could be concluded that the influence
      of flow on the lag time was minimal and that the inoculation of the pesticide
      primed soil had a little surplus value on degradation.

PMID- 20696512
TI  - Response to Dr. Franska's comments on the paper "Antibiotic removal from water:
      Elimination of amoxicillin and ampicillin by microscale and nanoscale iron
      particles." Ghauch et al. (2009) Environmental Pollution 157, 1626-1635.

PMID- 20696513
TI  - Transport and degradation of pesticides in a biopurification system under
      variable flux, Part I: a microcosm study.
AB  - The efficiency of a biopurification system, developed to treat pesticide
      contaminated water, is to a large extent determined by the chemical and hydraulic
      load. Insight into the behaviour of pesticides under different fluxes is
      necessary. The behaviour of metalaxyl, bentazone, linuron, isoproturon and
      metamitron was studied under three different fluxes with or without the presence
      of pesticide-primed soil in column experiments. Due to the time-dependent
      sorption process, retention of the pesticides with intermediate mobility was
      significantly influenced by the flux. The higher the flux, the slower pesticides
      will be sorbed, which resulted in a lower retention. Degradation of the
      intermediate mobile pesticides was also submissive to variations in flux. An
      increase in flux, led to a decrease in retention, which in turn decreased the
      opportunity time for biodegradation. Finally, the presence of pesticide-primed
      soil was only beneficial for the degradation of metalaxyl.

PMID- 20696514
TI  - Plant and soil surface responses to a combination of shrub removal and grazing in
      a shrub-encroached woodland.
AB  - Shrub encroachment into open woodland is a widespread phenomenon in semi-arid
      woodlands worldwide. Encroachment or woody thickening, is thought to result from
      overgrazing, changes in fire regimes and increased atmospheric carbon dioxide
      concentrations. Eighteen years after one-off shrub removal by ploughing we
      assessed the effects of four different land management systems resulting from two
      levels each of grazing (grazed, ungrazed) with and without ploughing, on the
      cover of landscape units, soil surface condition, diversity of understorey plants
      and density of shrubs. We recorded 2-7 times more patches under conventional
      conservation (unploughed-ungrazed) than the others treatments, and plant cover
      and diversity were greater on the two conservation (ungrazed) plots, irrespective
      of ploughing. Soils under shrubs and log mounds had greater indices of
      infiltration, stability and nutrients. Shrub density under the active pastoral
      (ploughed-grazed) treatment was two and a half times greater than that in other
      treatments, but results were not significant. The effects of different treatments
      on shrubs were largely species-specific. Overall, our results suggest that
      ploughing does not provide long-term control of encroaching shrubs.

PMID- 20696515
TI  - Life cycle assessment of nutrient remediation and bioenergy production potential
      from the harvest of hydrilla (Hydrilla verticillata).
AB  - Hydrilla (Hydrilla verticillata) is one of the world's most problematic invasive
      aquatic plants. Although management of hydrilla overgrowth has often been based
      on use of chemical herbicides, issues such as the emergence of herbicide
      resistant hydrilla biotypes and the need for in situ nutrient remediation
      strategies have together raised interest in the use of harvester machines as an
      alternative management approach. Using a life cycle assessment (LCA) approach, we
      calculated a range of net energy and economic benefits associated with hydrilla
      harvests and the utilization of biomass for biogas and compost production. Base
      case scenarios that used moderate data assumptions showed net energy benefit
      ratios (NEBRs) of 1.54 for biogas production and 1.32 for compost production
      pathways. NEBRs for these respective pathways rose to 2.11 and 2.68 when labor
      was excluded as a fossil fuel input. Base case biogas and compost production
      scenarios respectively showed a monetary benefit cost ratio (BCR) of 1.79 and
      1.83. Moreover, very high NEBRs (3.94 for biogas; 6.37 for compost) and BCRs (>11
      for both biogas and compost) were found for optimistic scenarios in which
      waterways were assumed to have high hydrilla biomass density, high nutrient
      content in biomass, and high priority for nutrient remediation. Energy and
      economic returns were largely decoupled, with biogas and fertilizer providing the
      bulk of output energy, while nutrient remediation and herbicide avoidance
      dominated the economic output calculations. Based on these results, we conclude
      that hydrilla harvest is likely a suitable and cost-effective management program
      for many nutrient-impaired waters. Additional research is needed to determine how
      hydrilla harvesting programs may be most effectively implemented in conjunction
      with fish and wildlife enhancement objectives.

PMID- 20696516
TI  - Does performance evaluation help public managers? A Balanced Scorecard approach
      in urban waste services.
AB  - The urban waste market has evolved significantly in the past decades, which among
      other changes, has led to the creation of new utilities and new business models.
      However, very few things have changed for the users. Urban waste collection
      remains mainly under the responsibility of local authorities and the charges paid
      by the users in most countries are very low compared to the provision costs. This
      situation forces the injection of public money into the system, encouraging the
      'quiet-life' within the utilities and, therefore, inefficiency. The present study
      intends to analyze the potential for the application of the Balanced Scorecard
      (BSc) methodology into the waste utilities. After a comprehensive revision of the
      urban waste sector in Portugal, the methodology of BSc and its application in
      local public services is described and discussed. Focusing on implementation
      rather than on strategy, a set of performance indicators is proposed to be
      utilized in the different management models of waste utilities in Portugal: the
      municipalities, semi-autonomous utilities, municipal companies and mixed
      companies. This implementation is then exemplified through four case studies, one
      for each type of utility. This paper provides a flexible framework proposal to be
      applied to waste utilities operating both in Portugal and abroad.

PMID- 20696517
TI  - Attribute-based analysis of hunters' lease preferences.
AB  - Understanding of hunter preferences for hunting lease attributes is important to
      landowners because such knowledge provides key information for managing and
      marketing fee-hunting in order to maximize revenues. Premised on this insight, we
      used attribute based modeling to investigate how hunter preferences for potential
      leases were influenced by lease and hunter-specific attributes. A mail survey of
      Mississippi licensed hunters provided the necessary data. Estimation results
      based on McFadden conditional logit regression suggested that lease attributes
      including game diversity, lease location relative to hunter residence, lease
      size, lease duration and lease rate influenced willingness to pay for additional
      units of lease attributes. Depending on the specific levels of these attributes,
      WTP could vary as much as $5.70 per acre. Of the hunter-specific attributes, age
      and income significantly influenced hunter decision to buy a lease or opt for
      status quo. Results of this study should assist landowners in increasing
      financial returns from fee-hunting endeavors through appropriate changes to their
      hunting access policies and wildlife management activities in response to hunter
      preferences regarding lease attributes.

PMID- 20696518
TI  - Removal of nutrients and veterinary antibiotics from swine wastewater by a
      constructed macrophyte floating bed system.
AB  - The potential of three varieties of Italian ryegrass (Lolium multiflorum Lam.),
      Dryan, Tachimasari and Waseyutaka, to improve the water quality of swine
      wastewater was evaluated using a constructed macrophyte floating bed system. With
      respect to reductions in levels of nutrients, chemical oxygen demand (COD), and
      sulfonamide antimicrobials (SAs, including sulfadiazine, sulfamethazine, and
      sulfamethoxazole), Dryan performed better than Tachimasari and Waseyutaka. For
      Dryan, total N was reduced by 84.0%, total P by 90.4%, COD by 83.4% and
      sulfonamide antimicrobials by 91.8-99.5%. Similar results were observed for
      Tachimasari and Waseyutaka. The results indicated that the treatment of swine
      wastewater using the constructed macrophyte floating bed system was effective in
      the removal of nutrients and veterinary antibiotics.

PMID- 20696519
TI  - Re: Florian Jentzmik, Carsten Stephan, Kurt Miller, et al. Sarcosine in urine
      after digital rectal examination fails as a marker in prostate cancer detection
      and identification of aggressive tumours. Eur Urol 2010;58:12-8.

PMID- 20696520
TI  - Removal natural organic matter by coagulation-adsorption and evaluating the
      serial effect through a chlorine decay model.
AB  - The removal of natural organic matter (NOM) by coagulation and adsorption on
      modified wheat straw (MWS) was investigated. Two types of inorganic polymer
      coagulants, polyferric chloride (PFC) and polyaluminum chloride (PAC), were used
      during experiments. The removal efficiency of NOM in terms of UV(254), DOC and
      COD(Mn) increased with the dosage of coagulants and adsorbent increasing.
      Combined coagulation and adsorption showed better UV(254) and turbidity removal
      efficiency (61.8% and 95.8% respectively for PFC-MWS, and 61.5% and 94.2%
      respectively for PAC-MWS) than individual treatment. The effects of combination
      sequences on DOC fractionation and residual chlorine decay were analyzed and the
      chlorine data were fitted using a chlorine decay model. In general, the higher
      the molecular weight of NOM was, the better removal efficiency the combined
      treatment can achieve. MWS can enhance the removal of NOM with higher molecular
      weight. The disinfection by-products (DBPs) formation potential in the effluents
      from coagulation and subsequent adsorption was greater than that in the effluents
      from adsorption and subsequent coagulation.

PMID- 20696521
TI  - Sensitive determination of mercury by a miniaturized spectrophotometer after in
      situ single-drop microextraction.
AB  - An in situ single-drop microextraction (SDME) method was developed for trace
      mercury determination by a miniaturized spectrophotometer, in which a simple and
      cheap light-emitting diode (LED) was employed as the light source, and a handheld
      charge coupled device (CCD) was served as the detector. A droplet of 0.006%
      dithizone-CCl(4) (m/v) was used as extraction phase and hanged on a rolled PTFE
      tube. LED light was adjusted carefully to pass through the centre of the droplet
      and the entrance slit of the CCD detector. The radiation intensities of 475 nm
      before and after SDME (I(0) and I(i)) were recorded for quantification. Under the
      optimum conditions, the system provided a linear range of 2-50 MUg L(-1), with a
      correlation coefficient of 0.9983 and a limit of detection (3sigma) of 0.2 MUg L(
      1). The enrichment factor was about 69. The present method showed the merits of
      high sensitivity, simplicity, rapidity, low reagent consumption and field
      analysis potential. Finally, this method was successfully applied for the
      determination of the total mercury in spiked tap water sample, spiked river water
      sample and certified reference material (GBW (E) 080393, simulated water).

PMID- 20696522
TI  - Potential for biodegradation and sorption of acetaminophen, caffeine, propranolol
      and acebutolol in lab-scale aqueous environments.
AB  - Sorption and combined sorption-biodegradation experiments were conducted in
      laboratory batch studies with 100 g soil/sediments and 500 mL water to
      investigate the fates in aqueous environments of acetaminophen, caffeine,
      propranolol, and acebutolol, four frequently used and often-detected
      pharmaceuticals. All four compounds have demonstrated significant potential for
      degradation and sorption in natural aqueous systems. For acetaminophen,
      biodegradation was found to be a primary mechanism for degradation, with a half
      life (t(1/2)) for combined sorption-biodegradation of 2.1 days; in contrast,
      sorption alone was responsible only for a 30% loss of aqueous-phase acetaminophen
      after 15 days. For caffeine, both biodegradation and sorption were important
      (t(1/2) for combined sorption-biodegradation was 1.5 days). However, for
      propranolol and acebutolol, sorption was found to be the most significant removal
      mechanism and was not affected by biodegradation. Desorption experiments revealed
      that the sorption process was mostly irreversible. High values were found for
      K(d) for caffeine, propranolol, and acebutolol, ranging from 250 to 1900 L kg(
      1), which explained their greater tendency for sorption onto sediments, compared
      to the more hydrophilic acetaminophen. Experimentally derived values for logK(oc)
      differed markedly from values calculated from correlation equations. This
      discrepancy was attributed to the fact that these equations are well suited for
      hydrophobic interactions but may fail to predict the sorption of polar and ionic
      compounds. These results suggest that mechanisms other than hydrophobic
      interactions played an important role in the sorption process.

PMID- 20696524
TI  - Modifiable risk factors for incidence of pain in older adults.
AB  - Pain symptoms in aging populations have significant public health impact. The aim
      of this study was to determine risk factors for the incidence of pain in older
      adults, focusing on those factors that can be modified. Secondary analyses were
      performed of survey data from the nationally representative Health and Retirement
      Study of US adults older than 50 years. Generalized estimating equations logistic
      regressions were used to evaluate the effect of selected variables on the
      incidence of pain using biennial (1992 through 2006) data, determining the
      relationship between the incidence of pain and the potential risk factors. Of the
      18,439 survey respondents in 2006, 34.1% (95% CI: 33.2%, 35.0%) reported that
      they were often troubled by pain; 24.3% reported having moderate to severe pain;
      and 22.3% reported that their daily life was affected by pain. Between 1992 and
      2006, 7967 individuals reported new onset of pain in 169,762 person-years of
      follow-up, an incidence of 4.69 (4.59, 4.80) per 100 person-years. Depression and
      being overweight were independent predictors associated with an increased
      likelihood of incident pain. Current smoking increased the likelihood of incident
      pain only in those subjects who also reported depression. In conclusion, pain is
      a common symptom in older adults. Depression, smoking, and overweight are
      potentially modifiable risk factors and could be considered in the prevention and
      management of pain in older adults.

PMID- 20696523
TI  - Spinal cord protein interacting with C kinase 1 is required for the maintenance
      of complete Freund's adjuvant-induced inflammatory pain but not for incision
      induced post-operative pain.
AB  - Protein interacting with C kinase 1 (PICK1) is a PDZ-containing protein that
      binds to AMPA receptor (AMPAR) GluR2 subunit and protein kinase Calpha (PKCalpha)
      in the central neurons. It functions as a targeting and transport protein,
      presents the activated form of PKCalpha to synaptic GluR2, and participates in
      synaptic AMPAR trafficking in the nervous system. Thus, PICK1 might be involved
      in many physiological and pathological processes triggered via the activation of
      AMPARs. We report herein that PICK1 knockout mice display impaired mechanical and
      thermal pain hypersensitivities during complete Freund's adjuvant (CFA)-induced
      inflammatory pain maintenance. Acute transient knockdown of spinal cord PICK1
      through intrathecal injection of PICK1 antisense oligodeoxynucleotide had a
      similar effect. In contrast, knockout and knockdown of spinal cord PICK1 did not
      affect incision-induced guarding pain behaviors or mechanical or thermal pain
      hypersensitivities. We also found that PICK1 is highly expressed in dorsal horn,
      where it interacts with GluR2 and PKCalpha. Injection of CFA into a hind paw, but
      not a hind paw incision, increased PKCalpha-mediated GluR2 phosphorylation at
      Ser880 and GluR2 internalization in dorsal horn. These increases were absent when
      spinal cord PICK1 was deficient. Given that dorsal horn PKCalpha-mediated GluR2
      phosphorylation at Ser880 and GluR2 internalization contribute to the maintenance
      of CFA-induced inflammatory pain, our findings suggest that spinal PICK1 may
      participate in the maintenance of persistent inflammatory pain, but not in
      incision-induced post-operative pain, through promoting PKCalpha-mediated GluR2
      phosphorylation and internalization in dorsal horn neurons.

PMID- 20696525
TI  - A peripherally restricted cannabinoid receptor agonist produces robust anti
      nociceptive effects in rodent models of inflammatory and neuropathic pain.
AB  - Cannabinoids are analgesic in man, but their use is limited by their psychoactive
      properties. One way to avoid cannabinoid receptor subtype 1 (CB1R)-mediated
      central side-effects is to develop CB1R agonists with limited CNS penetration.
      Activation of peripheral CB1Rs has been proposed to be analgesic, but the
      relative contribution of peripheral CB1Rs to the analgesic effects of systemic
      cannabinoids remains unclear. Here we addressed this by exploring the analgesic
      properties and site of action of AZ11713908, a peripherally restricted CB1R
      agonist, in rodent pain models. Systemic administration of AZ11713908 produced
      robust efficacy in rat pain models, comparable to that produced by WIN 55, 212-2,
      a CNS-penetrant, mixed CB1R and CB2R agonist, but AZ11713908 generated fewer CNS
      side-effects than WIN 55, 212-in a rat Irwin test. Since AZ11713908 is also a
      CB2R inverse agonist in rat and a partial CB2R agonist in mouse, we tested the
      specificity of the effects in CB1R and CB2R knock-out (KO) mice. Analgesic
      effects produced by AZ11713908 in wild-type mice with Freund's complete adjuvant
      induced inflammation of the tail were completely absent in CB1R KO mice, but
      fully preserved in CB2R KO mice. An in vivo electrophysiological assay showed
      that the major site of action of AZ11713908 was peripheral. Similarly,
      intraplantar AZ11713908 was also sufficient to induce robust analgesia. These
      results demonstrate that systemic administration of AZ11713908, produced robust
      analgesia in rodent pain models via peripheral CB1R. Peripherally restricted CB1R
      agonists provide an interesting novel approach to analgesic therapy for chronic
      pain.

PMID- 20696526
TI  - The necessity of animal models in pain research.
AB  - There exists currently a fair degree of introspection in the pain research
      community about the value of animal research. This review represents a defense of
      animal research in pain. We discuss the inherent advantage of animal models over
      human research as well as the crucial complementary roles animal studies play vis
      a-vis human imaging and genetic studies. Finally, we discuss recent developments
      in animal models of pain that should improve the relevance and translatability of
      findings using laboratory animals. We believe that pain research using animal
      models is a continuing necessity-to understand fundamental mechanisms, identify
      new analgesic targets, and inform, guide and follow up human studies-if novel
      analgesics are to be developed for the treatment of chronic pain.

PMID- 20696527
TI  - A combined environmental straining specimen holder for high-voltage electron
      microscopy.
AB  - A novel specimen holder that enables in situ observation of crack-tip deformation
      and/or fracture under a controlled environment is developed for a high-voltage
      electron microscope (HVEM). A window-type environmental cell (EC) that
      incorporates a uniaxial straining apparatus is built into a side-entry-type
      single-tilt specimen holder. The gas control in EC, straining apparatus design,
      limited field of view for crack-tip observation, and specimen preparation for the
      specimen holder are presented in detail. Experimental results successfully
      demonstrate that the developed specimen holder is quite useful for the dynamic
      observation of crack-tip deformation and/or fracture subjected to a hostile
      environment, such as hydrogen gas.

PMID- 20696528
TI  - GPR30 co-localizes with cholinergic neurons in the basal forebrain and enhances
      potassium-stimulated acetylcholine release in the hippocampus.
AB  - GPR30 is a novel, membrane-bound, G-protein coupled estrogen receptor (Filardo et
      al., 2002; Prossnitz et al., 2008). We hypothesize that GPR30 may mediate effects
      of estradiol (E2) on basal forebrain cholinergic neurons and cognitive
      performance. Recently we showed that G-1, a selective GPR30 agonist, enhances the
      rate of acquisition on a delayed matching-to-position (DMP) T-maze task (Hammond
      et al., 2009). In the present study, we examined the distribution of GPR30 in the
      rat forebrain, and the effects of G-1 on potassium-stimulated acetylcholine
      release in the hippocampus. GPR30-like immunoreactivity was detected in many
      regions of the forebrain including the hippocampus, frontal cortex, medial
      septum/diagonal band of Broca, nucleus basalis magnocellularis and striatum.
      GPR30 mRNA also was detected, with higher levels in the hippocampus and cortex
      than in the septum and striatum. Co-localization studies revealed that the
      majority (63-99%) of cholinergic neurons in the forebrain expressed GPR30-like
      immunoreactivity. A far lower percentage (0.4-42%) of GABAergic (parvalbumin
      containing) cells also contained GPR30. Sustained administration of either G-1 or
      E2 (5 MUg/day) to ovariectomized rats produced a nearly 3-fold increase in
      potassium-stimulated acetylcholine release in the hippocampus relative to vehicle
      treated controls. These data demonstrate that GPR30 is expressed by cholinergic
      neurons in the basal forebrain, and suggest that activation of GPR30 enhances
      cholinergic function in the hippocampus similar to E2. This may account for the
      effects of G-1 on DMP acquisition previously reported.

PMID- 20696529
TI  - Developmental validation of a point-of-care, salivary alpha-amylase biosensor.
AB  - The translation of salivary alpha-amylase (sAA) to the ambulatory assessment of
      stress hinges on the development of technologies capable of speedy and accurate
      reporting of sAA levels. Here, we describe the developmental validation and
      usability testing of a point-of-care, colorimetric, sAA biosensor. A disposable
      test strip allows for streamlined sample collection and a corresponding hand-held
      reader with integrated analytic capabilities permits rapid analysis and reporting
      of sAA levels. Bioanalytical validation utilizing saliva samples from 20 normal
      subjects indicates that, within the biosensor's linear range (10-230 U/ml), its
      accuracy (R(2)=0.989), precision (CV<9%), and measurement repeatability (range 
      3.1% to +3.1%) approach more elaborate laboratory-based, clinical analyzers. The
      truncated sampling-reporting cycle (<1 min) and the excellent performance
      characteristics of the biosensor has the potential to take sAA analysis out of
      the realm of dedicated, centralized laboratories and facilitate future sAA
      biomarker qualification studies.

PMID- 20696530
TI  - The problem of "just for fun": patterns of use situations among active club drug
      users.
AB  - Existing research has demonstrated the significance of situational antecedents to
      substance use. The current study used a cluster analytic approach to identify
      groups of club drug users who report using substances in similar situations
      (assessed by the Inventory of Drug Taking Situations) with longitudinal data from
      400 active drug users. A three-cluster solution emerged in baseline data and was
      replicated in 12-month follow-up data. Groups were identified as Situationally
      Restricted, Pleasure Driven, and Situationally Broad users. Group differences
      were observed on measures of mental health, attitudes towards substance use,
      amount of substance use, and rates of substance dependence. Cluster membership
      predicted substance dependence after controlling for past dependence, current
      use, and current depression/anxiety.

PMID- 20696531
TI  - In large litters birth weight and gender is decisive for growth performance but
      less for carcass and pork quality traits.
AB  - This study aimed to examine whether growth performance, carcass and meat quality
      traits differed among high (H), medium (M) and low (L) birth weight (BtW) gilts
      and barrows born from large litters (>16 piglets born alive). Regardless of
      gender, H pigs grew faster (P<0.05) during the suckler period than L and M pigs.
      From weaning to slaughter at 113 kg catch-up growth was observed in M barrows. In
      gilts and barrows percentage ham was greater (P<0.05) and percentage total
      subcutaneous fat was lower (P<0.10) in H compared to M and L pigs. Compared to L
      and M pigs, H pigs displayed in general better quality in the longissimus muscle
      whereas the opposite was observed in the semitendinosus muscle. The superiority
      of H compared to M and L BtW littermates regarding carcass and meat quality
      appears to be less evident when pigs originate from large litters.

PMID- 20696532
TI  - Prevalence and risk factors for bruises in Chilean bovine carcasses.
AB  - Records of cattle slaughtered at two Chilean slaughterhouses (SLH1 and SLH2) were
      used to determine prevalence and risk factors for carcasses with bruises. Bruise
      prevalence amounted to 12.3% but differed between slaughterhouses (20.8% for SLH1
      and 8.6% for SLH2 respectively). Bruise severity grade 1 (mild) was most
      frequently recorded. The type of the animal, source of animal, the level of fat
      cover and lairage time were associated with the presence of bruises. Older
      categories of animals and animals that pass through a market before being moved
      to the slaughterhouse are more prone to show bruises. The results also indicate
      that under the reported Chilean circumstances animals that have longer lairage
      times (over 12 h) have a significantly reduced risk for bruises, except for oxen.
      Presence of bruises is also significantly associated with increased carcass pH
      values.

PMID- 20696533
TI  - Sensory quality of beef from different finishing diets.
AB  - Beef production under different local husbandry systems might have meat sensory
      quality implications for the marketing of these products abroad. In order to
      assess the effect of finishing diet systems on beef quality, a trained sensory
      taste panel assessed meat aged for 20 days from 80 Uruguayan Hereford steers that
      were finished on one of the following diets: T1=Pasture [4% of animal live weight
      (LW)], T2=Pasture [3% LW plus concentrate (0.6% LW)], T3=Pasture [3% LW plus
      concentrate (1.2% LW)], or T4=Concentrate plus hay ad libitum. Beef odour and
      flavour intensities decreased with an increase in the energy content of the diet.
      The meat from T2 had the lowest acid flavour and strange odours intensities. In
      general, steers fed only concentrate plus hay (T4) produced meat that had an
      inferior sensory quality because they had more pronounced off-flavours and was
      tougher.

PMID- 20696534
TI  - Tyrosine- and histidine-decarboxylase positive lactic acid bacteria and
      enterococci in dry fermented sausages.
AB  - Lactic acid bacteria (LAB) and enterococci were isolated immediately after
      stuffing (day 0), at the end of ripening (28th day) and at the end of storage
      (112th day) from dry fermented sausages produced by two different producers (K;
      R) in two diameters (4.5 and 7 cm) using either of two spice mixtures (P; H) and
      either of two starter cultures (Pediococcus pentosaceus, C; Lactobacillus
      curvatus+Staphylococcus carnosus, F), resulting in a total of 16 different
      combinations. Tyrosine-decarboxylase DNA sequence (tyrdc) was identified on
      average in 88% and 44% of enterococci and LAB isolates, respectively at the end
      of ripening, the corresponding figures regarding histidine-decarboxylase gene
      sequence (hisdc) was 71% and 16%, respectively. Lactobacillus plantarum, L.
      brevis and L. casei/paracasei, and Enterococcus faecium and Enterococcus faecalis
      were identified as tyramine/histamine producers in the sausages.

PMID- 20696535
TI  - Age and nutrition influence the concentrations of three branched chain fatty
      acids in sheep fat from Australian abattoirs.
AB  - The characteristic mutton odour, associated with the cooked meat of older sheep,
      can be problematic for some consumers who find the odour disagreeable. Branch
      chain fatty acids (BCFAs) are considered to be the main determinants of mutton
      odour. In this study, the aim was to identify the factors influencing the BCFA
      content of animals at abattoirs in Australia. Samples of subcutaneous fat from
      over the chump (gluteus medius) were collected from 533 sheep carcasses at
      abattoirs in New South Wales, Victoria and Western Australia. The carcasses were
      from sheep differing in age, gender, breed and nutrition. The concentrations of
      three branched chain fatty acids (BCFAs); namely, 4-methyloctanoic (MOA), 4
      ethyloctanoic (EOA) and 4-methylnonanoic acids (MNA), were determined.
      Statistical modelling showed that, with pre-slaughter nutrition in the model as a
      random term, BCFA concentrations could be used for discriminating the age of
      sheep. Fat samples from lamb carcasses had lower MOA and EOA concentrations and a
      higher concentration of MNA in comparison to hogget and mutton (P<0.05). When
      nutrition was excluded as a random effect from the statistical model, the MOA and
      MNA concentrations did not differentiate between lamb, hogget and mutton whereas,
      for EOA, lamb had a lower concentration than mutton (P<0.05) with hogget
      intermediate. An interaction existed between age and gender (P<0.05) where female
      lambs had lower EOA concentrations relative to the mutton but not for castrates.

PMID- 20696536
TI  - Effects of lactate/phosphate injection enhancement on oxidation stability and
      protein degradation in early postmortem beef cuts packaged in high oxygen
      modified atmosphere.
AB  - The influence of lactate/phosphate enhancement on meat color and lipid oxidation
      stability, tenderness, protein degradation, and protein aggregation of early
      postmortem beef muscles packaged in a high oxygen modified atmosphere packaging
      (HiOx-MAP; 80% O2, 20% CO2) were studied. At 24 hr postmortem, three bovine
      muscles (longissimus, semimembranosus, and adductor; n=10, respectively) were
      enhanced (10% injection rate) with either lactate (2.5%)/phosphate (0.3%)
      solution or water, packaged in HiOx-MAP, stored 9 days at 1 degrees C, and then
      displayed for 7 days at 1 degrees C. The lactate/phosphate injection
      significantly improved color stability (higher a* values) of all three bovine
      muscles throughout display period. Accumulation of lipid oxidation determined by
      2-thiobarbituric acid-reactive substances values was also decreased (P<0.05) in
      the lactate/phosphate injection compared to the water treatment during storage
      and display periods. The objective tenderness values of longissimus and
      semimembranosus were also improved (P<0.05) by the lactate/phosphate enhancement
      treatment compared to the water treatment based on star probe measurement. There
      were no significant differences found in desmin and troponin-T degradation, or
      oxidative cross-linking of myosin between treatments. The results suggest that
      lactate/phosphate enhancement has beneficial effects on color and lipid oxidation
      stability, and tenderness development of beef cuts under HiOx-MAP conditions.

PMID- 20696537
TI  - Mitotically active cellular luteinized thecoma of the ovary and luteinized
      thecomatosis associated with sclerosing peritonitis: case studies, comparison,
      and review of the literature.
AB  - In this study, we distinguish two clinical and pathological entities that are
      similarly named: luteinized thecoma and luteinized thecoma associated with
      sclerosing peritonitis. Ovarian luteinized thecoma lacks definitive criteria for
      malignancy. Based on our case study of a mitotically active neoplasm without
      nuclear atypia in which the patient was living and well 19 years after operation
      and comparison with prior studies of luteinized thecoma and the closely related
      entity of cellular fibroma, we propose presumptive criteria for malignancy for
      this rare neoplasm. Increased mitotic activity in luteinized thecoma without
      significant nuclear atypia is not an indication of malignant behavior, and such
      cases should therefore be referred to as mitotically active cellular luteinized
      thecoma. We also contrast neoplasms in the luteinized thecoma category with the
      entity originally reported as luteinized thecoma associated with sclerosing
      peritonitis. In the latter, the ovarian stromal proliferations are typically
      bilateral, can have an exceedingly high mitotic rate as was seen in our
      illustrative case, often incorporate non-neoplastic ovarian structures at their
      periphery, and are responsive to medical therapy. In our patient with sclerosing
      peritonitis, both the ovarian masses and peritoneal sclerosis underwent complete
      regression following treatment with gonadotropin-releasing hormone agonist and
      high doses of steroids, and an ovarian biopsy taken 2 months after therapy showed
      a histologically normal ovary. The patient subsequently became pregnant and
      delivered a normal infant. This is, to our knowledge, the first case of
      successful medically conservative treatment of a young patient with this entity
      that led to complete relief of symptoms and allowed preservation of fertility.
      Because recent observations support the non-neoplastic nature of the ovarian
      stromal proliferations, we advocate use of the previously proposed term
      luteinized thecomatosis associated with sclerosing peritonitis for this entity.

PMID- 20696538
TI  - A comparison of delay discounting among smokers, substance abusers, and non
      dependent controls.
AB  - Previous studies have shown that smokers and substance-dependent individuals
      discount rewards that are available after a delay more than individuals without a
      history of substance dependence. However, it is not clear whether delay
      discounting is similar among smokers and substance-dependent individuals.
      Further, the influence of the combination of smoking and other substance
      dependence on delay discounting remains unknown. The present study compared the
      performance of four groups of individuals on a delay discounting task. The groups
      were (a) heavy smokers with comorbid substance dependence, (b) heavy smokers with
      no history of substance dependence, (c) never smokers with comorbid substance
      dependence, and (d) never smokers with no history of substance dependence.
      Analysis revealed that individuals who smoked and/or were dependent on another
      substance discounted delayed rewards more than individuals with no history of
      smoking or other substance dependence. No differences in the task performance of
      heavy smokers and substance-dependent individuals were found. Notably,
      participants who were dependent on multiple substances did not discount delayed
      rewards more than those dependent on only one substance. Overall, findings
      indicate that smoking and other substance dependence are similarly related to
      delay discounting.

PMID- 20696540
TI  - Are former late-preterm children at risk for child vulnerability and
      overprotection?
AB  - BACKGROUND: Parent perception of child vulnerability (PPCV) and parent
      overprotection (POP) are believed to have serious implications for age
      appropriate cognitive and psychosocial development in very low birth weight
      preterm children. AIM: With recent concerns about suboptimal developmental
      outcomes in late-preterm children, this study was aimed at examining the
      relationship between history of late-preterm birth (34-36 6/7 weeks gestation),
      and PPCV, POP, and healthcare utilization (HCU). STUDY DESIGN: This was a cross
      sectional observational design. PARTICIPANTS: Study participants were mothers of
      54 healthy singleton children recruited from community centers including Women
      and Children Clinics (WIC), primary care clinics and daycare centers in the upper
      Midwest region. OUTCOME MEASURES: Outcome measures included Forsyth Child
      Vulnerability Scale (CVS), Thomasgard Parent Protection Scale (PPS) scores, and
      healthcare utilization (HCU). Potential covariates included history of life
      threatening illness, child and maternal demographics, and maternal stress and
      depression using the Center for Epidemiologic Studies Depression Scale (CESD).
      RESULTS: HCU (p=0.02) and the PPS subscales of supervision (p=0.003) and
      separation (p=0.03) were significant predictors of PPCV in mothers of 3-8 years
      old children with late-preterm history. Age of the child (p=0.008) and CVS scores
      (p=0.005) were significant predictors of POP. Maternal age (p=0.04), stress
      (p=0.04), and CVS scores (p=0.003) were significant predictors of HCU.
      Dependence, a subscale of the PPS, correlated with the child's age and gender
      even after controlling for age. CONCLUSION: History of late-preterm did not
      predict MPCV, MOP, or HCU in healthy children. Future research is needed in
      larger more diverse samples to better understand causal relationships and develop
      strategies to lessen risks of MPCV and MOP.

PMID- 20696539
TI  - Longitudinal study of respiratory infection patterns of breeding sows in five
      farrow-to-finish herds.
AB  - A longitudinal study was carried out in five French farrow-to-finish herds
      differently affected by respiratory diseases to describe the carrying and
      infection patterns of batches of sows to various respiratory pathogens during
      gestation and lactation. An entire batch of sows was followed during two
      successive reproduction cycles. Nasal, tonsillar and oro-pharyngeal swabs and
      blood samples were taken from each sow 9 and 4 weeks before farrowing and 1 and 4
      weeks after farrowing. Mycoplasma hyopneumoniae, Actinobacillus pleuropneumoniae,
      Pasteurella multocida, Haemophilus parasuis and Streptococcus suis were detected
      from swab samples using PCR assays. Blood samples were tested for antibodies
      against M. hyopneumoniae, A. pleuropneumoniae serotypes 1-9-11 and 2, Porcine
      Circovirus type-2 (PCV-2) and Porcine Reproductive and Respiratory Syndrome virus
      (PRRSV) by ELISA tests. Antibodies against H(1)N(1), H(1)N(2) and H(3)N(2) Swine
      Influenza Viruses (SIV) of European lineages were tested by hemagglutination
      inhibition assay. The results indicated that S. suis is widespread among sows
      (67.1% of PCR-positive sows). A. pleuropneumoniae, P. multocida, and H. parasuis
      were detected by PCR in 30.9%, 24.6% and 23.4% of the sows, respectively.
      Antibodies against M. hyopneumoniae were recovered from more than 55% of the sows
      in all herds whereas the micro-organism was detected in 2.4% of the sows.
      Although PCV-2 and SIV infections were highly prevalent, the PRRSV infection
      patterns ranged from no infection in farms mildly affected by respiratory
      diseases to active circulation in more severely affected herds. The sow
      population thus constitutes a reservoir for a continuous circulation of
      respiratory pathogens and needs to be properly considered in control strategies.

PMID- 20696541
TI  - The efficacy of sternal measurements for sex estimation in South African blacks.
AB  - The correct assessment of sex from the human skeleton is of fundamental
      importance in forensic medicine and bioarchaeology. In South Africa, unidentified
      remains are often fragmentary, making it necessary to estimate sex from a variety
      of skeletal elements. The purpose of the present study was to evaluate the sex
      discriminating potential of the sternum in black South Africans using standard
      osteometric techniques. A sample of 123 males and 83 females drawn from the
      Raymond A. Dart Collection of Human Skeletons and the Pretoria Bone Collection
      was used. The results demonstrated that all eight sternal variables, including
      both dimensions and indices, were highly sexually dimorphic in this population. A
      stepwise discriminant function procedure, which selected corpus sterni length and
      manubrium width, correctly identified 86.4% of the individuals in the study
      sample. Additional multivariate discriminant equations incorporating dimensions
      for either the manubrium or corpus sterni yielded sex prediction rates of 80.6%
      and 84.5%, respectively. Sternal area, when used in isolation, produced the
      highest sex classification accuracy with 86.9% of specimens correctly assigned.
      The remaining single variable functions, which can be applied when well-preserved
      or complete sterna are not available for analysis, provided classification
      accuracies ranging from 68.4% to 83.5%. These classification results are
      comparable to those reported in previous investigations concerning sex estimation
      of black South Africans for other postcranial elements.

PMID- 20696542
TI  - Quantitative assessment of pulmonary regurgitation in patients with and without
      right ventricular tract obstruction.
AB  - BACKGROUND: There are concerns whether there is a difference in clinical utility
      of pulmonary regurgitation (PR) fraction (PRF) and PR volume (PRV) in subgroups
      of patients with isolated PR and individuals with combined PR and right
      ventricular outflow tract obstruction (RVOTO). The aim of the study was to
      compare PRF and PRV in patients with or without RVOTO. METHODS AND RESULTS: 82
      consecutive patients after repair of tetralogy of Fallot (TOF) who underwent
      cardiovascular magnetic resonance and echocardiography were studied. There was no
      difference in PRF between patients with moderate and severe right ventricular
      (RV) dilatation (32+/-13% vs. 37+/-12%; p=0.18). Significant difference in PRV
      was observed between these groups (23+/-10 ml/m2 vs. 31+/-12 ml/m2, respectively;
      p=0.02). PRV had better ability than PRF in identification of severe RV
      dilatation, both in group with RVOTO [area under the curve (AUC) 0.82 vs. 0.72,
      p=0.005] and in patients without RVOTO (AUC 0.83 vs. 0.77, p=0.04). A strong
      correlation was seen between PRF and PRV both in patients with and without RVOTO
      [r=0.93, p<0.0001 and r=0.92, p<0.0001, respectively]. In both subgroups high
      variability of PRF was found in subjects with similar degree of PRV. CONCLUSIONS:
      PRV shows better ability than PRF in evaluating influence of PR on RV in patients
      after TOF repair, both in population with and without concomitant RVOTO.

PMID- 20696543
TI  - Expanding the reach of decision and communication aids in a breast care center: a
      quality improvement study.
AB  - OBJECTIVE: One academically based breast cancer clinic implements decision and
      communication aids as part of routine clinical care. This quality improvement
      study aimed to expand reach of these supportive materials and services with
      budget-neutral program changes. METHODS: We used program theory and continuous
      quality improvement to design changes to our program. We calculated reach as the
      number of new patient visits for which we administered decision and communication
      aids. We compared reach before and after the program changes. RESULTS: Program
      changes included: reassigning program outreach tasks from over-committed to under
      utilized personnel; deploying personnel in floating rather than fixed schedules;
      and creating a waitlist so service delivery was dynamically reallocated from
      overbooked to underbooked personnel. Before these changes, we reached 208
      visitors with decision aids, and 142 visitors with communication aids. Changes
      were associated with expanded reach, culminating in program year 2008 with the
      delivery of 936 decision aids and 285 communication aids. CONCLUSIONS: We
      observed over a fourfold increase in decision aid reach and a twofold increase in
      communication aid reach. We attribute increases to recent program changes.
      PRACTICE IMPLICATIONS: This study illustrates how program theory and quality
      improvement methods can contribute to expanded reach of decision and
      communication aids.

PMID- 20696544
TI  - Knowledge, satisfaction with information, decisional conflict and psychological
      morbidity amongst women diagnosed with ductal carcinoma in situ (DCIS).
AB  - OBJECTIVE: To assess knowledge, satisfaction with information, decisional
      conflict and psychological morbidity amongst women diagnosed with ductal
      carcinoma in situ (DCIS) and to explore the factors associated with less
      knowledge and greater confusion about DCIS. METHODS: A cross-sectional survey of
      women diagnosed with DCIS in Australia (N=144). RESULTS: This study found
      misunderstanding and confusion amongst women diagnosed with DCIS and a desire for
      more information about their breast disease. Approximately half of participants
      worried about their breast disease metastasizing; approximately half expressed
      high decisional conflict; 12% were anxious and 2% were depressed. Logistic
      regression analysis demonstrated that worry about dying from the breast disease
      was significantly associated with not knowing that DCIS could not metastasize (OR
      3.9; 95% CI 1.03-14.25); and confusion about whether DCIS could metastasize was
      significantly associated with dissatisfaction with information (OR 12.5; 95% CI
      3.8-40.2). CONCLUSION: Good communication about how DCIS differs from invasive
      breast cancer is essential to alleviating the confusion and worry amongst women
      with DCIS. PRACTICE IMPLICATIONS: Recommendations about how best to communicate a
      diagnosis of DCIS, including the uncertainties, are needed to guide health
      professionals to promote better understanding about DCIS and increase the well
      being of women with DCIS.

PMID- 20696545
TI  - [William Harvey, discoverer of blood circulation].

PMID- 20696546
TI  - Thoracic computed tomographic manifestations of tuberous sclerosis in adults.
AB  - The purpose of this article is to illustrate the various manifestations that can
      be encountered on thoracic computed tomography of tuberous sclerosis in adults.
      The pulmonary findings include lymphangioleiomyomatosis and multifocal
      micronodular pneumocyte hyperplasia. The extrapulmonary manifestations are
      divided into cardiac, vascular, mediastinal, osseous, and upper abdominal
      findings.

PMID- 20696547
TI  - Technology-aided verbal instructions to help persons with mild or moderate
      Alzheimer's disease perform daily activities.
AB  - These two studies extended previous research on the use of verbal instructions
      and support technology for helping persons with mild or moderate Alzheimer's
      disease perform daily activities. Study I included seven participants who were to
      carry out one of two previously targeted activities (i.e., either coffee
      preparation or table setting). Study II included four participants who were to
      carry out two new activities (i.e., preparation of a fruit salad and of a
      vegetable salad). The effects of activity engagement on mood (i.e., indices of
      happiness) were assessed by recording the participants' behavior during the
      activity trials and parallel non-activity periods. The participants of Study I
      reached percentages of correct activity performance, which normally exceeded 85.
      Five of them also showed higher indices of happiness during the activity trials
      as opposed to the non-activity periods. Three of the participants of Study II
      reached high percentages of correct performance on both activities available. One
      of these participants also showed higher indices of happiness during the activity
      trials. The findings were discussed in relation to previous research outcomes and
      in terms of their practical implications for intervention programs.

PMID- 20696548
TI  - Approximating the stability region of a neural network with a general
      distribution of delays.
AB  - We investigate the linear stability of a neural network with distributed delay,
      where the neurons are identical. We examine the stability of a symmetrical
      equilibrium point via the analysis of the characteristic equation both when the
      connection matrix is symmetric and when it is not. We determine a mean delay and
      distribution independent stability region. We then illustrate a way of improving
      on this conservative result by approximating the true region of stability when
      the actual distribution is not known, but some moments or cumulants of the
      distribution are known. Finally, we compare the approximate stability regions
      with the stability regions in the case of the uniform and gamma distributions. We
      show that the approximations improve as more moments or cumulants are used, and
      that the approximations using cumulants give better results than the ones using
      moments.

PMID- 20696549
TI  - Sonothrombolysis of intra-catheter aged venous thrombi using microbubble
      enhancement and guided three-dimensional ultrasound pulses.
AB  - BACKGROUND: Central venous and arterial catheters are a major source of
      thromboembolic disease in children. The investigators hypothesized that guided
      high-mechanical index (MI) impulses from diagnostic three-dimensional (3D)
      ultrasound during an intravenous microbubble infusion could dissolve these
      thrombi. METHODS: An in vitro system simulating intracatheter thrombi was created
      and then treated with guided high-MI impulses from 3D ultrasound, using low-MI
      microbubble sensitive imaging pulse sequence schemes to detect the microbubbles.
      Ten aged thrombi >24 hours old were tested using 3D ultrasound coupled with a
      continuous diluted microbubble infusion (group A) and 10 with 3D ultrasound alone
      (group B). RESULTS: The mean thrombus age was 28.6 hours (range, 26.6-30.3
      hours). Group A exhibited a 55 +/- 19% reduction in venous thrombus size compared
      with 31 +/- 10% in group B (P = .008). Feasibility testing was performed in four
      pigs, establishing an in vivo model to investigate further the efficacy of this
      approach. CONCLUSIONS: Sonothrombolysis of aged intracatheter venous thrombi can
      be achieved with commercially available microbubbles and guided high-MI
      ultrasound from a diagnostic 3D transducer.

PMID- 20696550
TI  - Color Doppler jet area overestimates regurgitant volume when multiple jets are
      present.
AB  - BACKGROUND: Color Doppler jet area (CDJA) is an important measure used to
      classify mitral regurgitation (MR) severity. The investigators hypothesized that
      the presence and configuration of multiple regurgitant jets can alter CDJA
      quantification for fixed regurgitant volumes. This has relevance to MR assessment
      prior to the treatment of valves with multiple regurgitant orifices or after
      surgical or percutaneous double-orifice mitral valve repair. METHODS: An in vitro
      model was developed to create jets flowing through a simulated mitral orifice
      into an imaging chamber. The flow loop was driven with a pulsatile pump at 60
      beats/min containing a water-glycerol solution approximating the viscosity of
      blood. At the orifice, simulated regurgitant stroke volumes of 2.5 to 25 mL were
      created through plates having either single openings with orifice areas from
      0.125 to 0.50 cm(2) or two to four openings with total orifice area of 0.25 cm(2)
      and varied linear spacing. An 8-MHz transthoracic two-dimensional ultrasound
      probe was used to acquire jet velocities by continuous-wave Doppler as well as
      color Doppler for offline analysis. CDJA values were obtained with custom
      automated pixel-counting software. RESULTS: Peak jet velocities ranged from 30 to
      550 cm/sec. For single jets, normalized average CDJA values increased nonlinearly
      as a function of average Reynolds number. Peak CDJA values were up to 62% higher
      for multiple jets compared with single jets with similar total orifice areas and
      simulated regurgitant stroke volumes. The presence or absence of multiple jets,
      rather than the total number of jets, appeared to have a greater effect on
      maximum CDJA. In addition, peak CDJA values for multiple jets increased with
      increased linear spacing. CONCLUSIONS: A fixed regurgitant volume involving
      multiple jets will have a larger CDJA value than the same total volume from a
      single jet. The source of this discrepancy appears to be increased ambient fluid
      entrainment from adjacent regurgitant jets. This potential overestimation of MR
      severity using color Doppler flow jets should be taken into consideration when
      assessing MR prior to treatment or when assessing residual MR after double
      orifice mitral valve repair.

PMID- 20696551
TI  - Exercise therapy correlates with improving renal function through modifying lipid
      metabolism in patients with cardiovascular disease and chronic kidney disease.
AB  - BACKGROUND: Patients with cardiovascular disease (CVD) and chronic kidney disease
      (CKD) are at high risk of cardiovascular mortality, thus therapies to improve
      renal function should be clinically investigated. METHODS AND RESULTS: We divided
      consecutive patients with CVD and CKD (n=19) into exercise (n=10) and non
      exercise (n=9) therapy groups. Exercise therapy for 12 weeks significantly
      improved the anaerobic metabolic threshold (AT-V O2) and high-density lipoprotein
      cholesterol (HDL-C) levels, and reduced triglyceride levels. Exercise therapy
      also improved estimated glomerular filtration rate (eGFR). Change in eGFR
      correlated significantly and positively with change in AT-V O2 and HDL-C, and
      negatively with change in triglyceride levels. CONCLUSIONS: Exercise therapy
      correlates with improving renal function in CVD patients with CKD through
      modifying lipid metabolism. Exercise therapy could be an effective clinical
      strategy to improve renal function.

PMID- 20696552
TI  - A comparison of pregabalin, lamotrigine, and placebo as adjunctive therapy in
      patients with refractory partial-onset seizures.
AB  - PURPOSE: This study assessed the comparative efficacy of pregabalin for
      refractory partial seizures. METHODS: Four-hundred and thirty-four patients with
      partial seizures were randomized to pregabalin, lamotrigine, or placebo as
      adjunctive therapy for 17 weeks of double-blind treatment. In phase I (11 weeks),
      pregabalin was titrated over 1 week and lamotrigine over 5 weeks to fixed dosages
      of 300mg/day for both. In phase II (6 weeks), patients not yet seizure-free were
      increased to pregabalin 600mg/day or lamotrigine 400mg/day. RESULTS: During phase
      I, there was a nonsignificant trend toward a greater reduction in seizures with
      pregabalin versus placebo and lamotrigine. Across the 17 weeks of treatment,
      pregabalin showed a median percentage reduction from baseline in seizure
      frequency of -20.0% (p=.001) versus placebo, and -9.7% (p=.080) versus
      lamotrigine. The responder rate (> or =50% reduction in seizure frequency) for
      pregabalin exceeded that of placebo (36% vs 21%; p=.007) and lamotrigine (36% vs
      24%; p=.04). Adverse events were consistent with the known safety profiles of
      pregabalin and lamotrigine. DISCUSSION: Pregabalin was demonstrated to be
      noninferior to lamotrigine in the treatment of refractory partial seizures.
      Overall conclusions were complicated by an unusually large and heterogeneous
      placebo response.

PMID- 20696553
TI  - Electroclinical characterization and classification of symptomatic epilepsies
      with very early onset by multiple correspondence analysis.
AB  - PURPOSE: To characterize very early onset symptomatic epilepsies
      electroclinically, to identify meaningful factors to delineate epilepsy syndromes
      under this category, and to test validity of the current syndromic organization
      of these epilepsies by the International League Against Epilepsy (ILAE). METHODS:
      Subjects were 38 epileptic patients with seizure onset before 3 months of age. We
      investigated the age of seizure onset, seizure types, myoclonus, EEG features,
      neuroimaging studies, outcome of seizures and development. We performed multiple
      correspondence analysis (MCA) to reveal associations among these characteristics
      and to find important characteristics to divide this epilepsy group into
      subgroups. RESULTS: Very early onset epilepsies were characterized by partial
      seizures and epileptic spasms, especially occurring in combination as a single
      ictal event (combined seizures), and poor outcome. Suppression-burst (SB),
      hypsarrhythmia, EEG asymmetry and structural brain abnormalities were common. MCA
      demonstrated that presence or absence of SB was the most meaningful factor to
      separate this group into subgroups. MCA on the subgroup with SB revealed a subset
      with early-onset spasms, partial seizures with single focus, no myoclonus, SB
      during wakefulness and sleep, no EEG asynchrony, hypsarrhythmia and combined
      seizures, and another subset with late-onset spasms, partial seizures with
      multiple foci, myoclonus, EEG asynchrony, no combined seizures, SB during sleep
      only, no EEG asymmetry, no structural abnormality and no hypsarrhythmia. These
      corresponded to Ohtahara syndrome and early myoclonic encephalopathy,
      respectively. CONCLUSIONS: Very early onset symptomatic epilepsies have the
      electroclinical characteristics distinct from those with later onset. This study
      supported the current ILAE organization on this epilepsy group from statistic
      approach.

PMID- 20696554
TI  - Ambras syndrome in a Korean patient with balanced pericentric inversion
      (8)(p11.2q24.2).

PMID- 20696555
TI  - Issues in biosecurity and biosafety.
AB  - The role of non-governmental organisations and other interested observers - civil
      society - has long been neglected by governments in the quest for a world secure
      from the threat of biological weapons or bioterrorism. New trends illustrate a
      greater appreciation of a strong need for a cooperative partnership. Governments
      need to accept and embrace some of these new trends and new technologies. At
      least since 2001 and the Amerithrax anthrax letters, the USA has had a
      significant focus on biosecurity and the related subject of biosafety.
      Biosecurity has also been raised to a place of prominence in security discussions
      throughout much of the rest of the globe, largely through the mechanisms of the
      Biological and Toxin Weapons Convention and related groups, but also through the
      World Health Organization and the implementation of the International Health
      Regulations, which is scheduled for 2012. Despite this attention, a clear
      understanding of the meanings of biosecurity and biosafety has yet to be
      achieved. Partly because of this lack of definition, and largely because of a
      broader understanding of the capabilities of the life sciences, many topics have
      begun to fall under the heading of biosecurity. This paper will not be able to
      explore all of these new topics but will instead attempt to present an overview
      of some of the issues at play today in the biosecurity dialogue.

PMID- 20696556
TI  - Dengue conundrums.
AB  - Dengue virus is the most common arboviral infection of humans in the tropical and
      subtropical regions of the world. This review briefly describes some of the
      challenges it presents. Dengue is an emerging disease; it is increasing in
      geographical distribution and severity, despite being significantly
      underreported. The World Health Organization case definition for the generally
      more severe manifestation of infection, dengue haemorrhagic fever (DHF), is
      controversial. The name DHF is something of a misnomer as the disease
      infrequently results in frank haemorrhage; the hallmark of DHF is actually plasma
      leakage. The existence of four closely related dengue virus serotypes contributes
      to difficulties in diagnosis and to original antigenic sin in the serological
      response to infection. The existence of multiple serotypes can result in more
      severe disease upon a second infection and complicates vaccine development.
      Nevertheless, a safe and effective vaccine is the greatest prospect for stemming
      the tide of dengue.

PMID- 20696557
TI  - The changing Brucella ecology: novel reservoirs, new threats.
AB  - Brucellosis is a zoonosis that preceded humans but continues to cause significant
      medical, veterinary and socioeconomic problems, mainly because its overall burden
      remains underestimated and neglected. Its ecology, or what we know of it, has
      evolved rapidly in recent years. Two novel species, Brucella ceti and B.
      pinnipedialis, with the potential for causing human disease have been isolated
      from marine mammals. Another novel species, B. microti, has been isolated from
      wildlife animals, whilst B. inopinata has been isolated from a human case. An
      active spillover of Brucella between domestic animals and wildlife is also being
      recognised, with elk transmitting B. abortus to cattle, and freshwater fish
      becoming infected with B. melitensis from waste meat. In recent years the global
      epidemiology of the disease has not altered drastically, apart from increased
      awareness of brucellosis in sub-Saharan Africa and a rapid expansion of disease
      endemicity in the Balkan Peninsula. Isolated stories and events underline that
      Brucella knows no borders. The modern world has offered the pathogen the ability
      to travel and manifest itself anywhere and has also offered scientists the
      ability to track these manifestations better than ever before. This may allow the
      disease to be neglected no longer, or at least to be recognised as neglected.

PMID- 20696558
TI  - A model of horizontal and vertical integration of teaching on the cadaveric
      heart.
AB  - This work was performed in a trial to organize the learning process by focusing
      on the integration of medical education particularly between the three main
      subjects: gross anatomy, histology and pathology. It was a theoretical teaching
      draft designed to be implemented with second year students of the Medical school
      of the King Abdul Aziz University, Jeddah, KSA, in order to overcome
      disadvantages in traditional teaching. The objectives of this work were to make
      medical students, at the pre-clinical stage of their medical carrier, alert to
      diagnosis and handling of clinical problems and to develop their ability to
      integrate pre-clinical and clinical subjects. Fifty human cadaveric hearts were
      anatomically and histopathologically examined. This examination revealed six
      different clinical problems such as pericarditis, myocarditis, cardiac
      hypertrophy, parasitic infestation, rheumatic heart disease and fatty
      infiltration. The medical students of the second year will be first introduced to
      the normal anatomical and histological structure of the heart, then allowed to
      visualize and examine the specimens of the cadaveric heart both macroscopically
      and microscopically. They will be introduced to a set of clinical problems
      through some clinical scenarios and asked to search for the possible etiological
      factors causing these changes, associated signs and symptoms. Finally they will
      be asked to present their findings and interpretations. This paper demonstrated a
      pathway of self-directed learning in an integrated teaching setting in the
      medical curriculum using available cadaveric material at a preparatory stage
      before developing the system-based curriculum.

PMID- 20696559
TI  - Modulation of the immune system by Boswellia serrata extracts and boswellic
      acids.
AB  - Extracts from the gum resin of Boswellia serrata and some of is constituents
      including boswellic acids affect the immune system in different ways. Among the
      various boswellic acids 11-keto-beta-boswellic acid (KBA) and acetyl-11-keto-beta
      boswellic acid have been observed to be active. However, also other boswellic
      acids may exhibit actions in the immune system. In the humoral defence system a
      mixture of boswellic acis at higher doses reduced primary antibody titres; on the
      other hand lower doses enhanced secondary antibody titres following treatment
      with sheep erythrocytes. In the cellular defence boswellic acides appear to
      increase lymphocyte proliferation whereas higher concentrations are even
      inhibitory. Moreover, BAs increase phagocytosis of macrophages. BAs affect the
      cellular defence system by interaction with production/release of cytokines.
      Thus, BAs inhibit activation of NFkappaB which is a product of neutrophile
      granulocytes. Consequently a down regulation of TNF-alpha and decrease of IL-1,
      IL-2, IL-4, IL-6 and IFN-gamma, which are proinflammatory cytokines by BEs and
      BAs has been reported. Suppressions of the classic way of the complement system
      was found to be due to inhibition of the conversion of C3 into C3a and C3b.
      However, which of these pharmacological actions contribute to the therapeutic
      effects and which is finally the best dosage of a standardized extract needs
      further examination. And it is also a question whether or not a single BA will
      have the same therapeutic effect as a standardized extract. Among the mediators
      of inflammatory reaction, mast cell stabilisation has been described by a BE.
      Inhibition of prostaglandin synthesis appears to play only a minor role as far as
      the anti-inflammatory effect is concerned. On the other hand the inhibitory
      action of BAs on 5-LO leading to a decreased production of leukotrienes has
      received high attention by the scientific community since a variety of chronic
      inflammatory diseases is associatied with increased leukotriene activity. At the
      end of the cascade of events in the cellular immune system as far as it directs
      to various tissues of the body - i.e. autoimmune diseases - formation of oxygen
      radicals and proteases (for example elastase) play an important destructive role.
      Here, BEs as well as BAs have been found to be inhibitory. From the
      pharmacological properties of BEs and BAs it is not surprising that positive
      effects of BEs in some chronic inflammatory diseases including rheumatoid
      arthritis, bronchial asthma, osteoarthritis, ulcerative colitis and Crohn's
      disease have been reported.

PMID- 20696560
TI  - The Cimicifuga racemosa special extract BNO 1055 prevents hot flashes in
      ovariectomized rats.
AB  - Hot flashes are a disorder of thermoregulation due to the lack of estrogens and
      are the most common and characteristic climacteric complaint. Hormone replacement
      therapy is the gold standard treatment but now its use is limited due to several
      side effects. Need therefore arises to search for non-estrogenic alternatives. It
      is well established that extracts of Cimicifuga racemosa (CR) ease climacteric
      complaints but solid animal experimental data supporting such effects are not
      available. The availability of sensitive transponders which record subcutaneous
      temperature continuously enables nowadays experiments in rats to establish
      whether they have hot flashes following ovariectomy (Seidlova-Wuttke et al. 2003)
      and if so, whether they can be influenced by the extract of CR BNO 1055. Intact
      Sprague-Dawley rats (n=16) were acclimatized and their subcutaneous body
      temperature was measured in 5 min intervals and mean values from 3h recordings
      were calculated. Thereafter, the rats were ovx and fed either with soy free (sf)
      or CR BNO 1055 (25 mg/animal/day) food. Temperature was recorded again after
      acute and sub-acute application of CR. In individual intact animals temperature
      was stable over the 3h recording period. Following ovx temperature pulses
      appeared with peaks occurring every 20-40 min. These fluctuations were not seen
      in CR BNO 1055 treated animals resulting in significantly higher mean
      temperatures in ovx in comparison to intact or ovx CR BNO treated rats. This
      reduction of hot flashes by BNO 1055 outlasted the experimental period of 3
      weeks. These results suggest that the ovx rats and the new temperature-sensitive
      device may be useful for the study of hot flashes. Furthermore the results prove
      that the CR BNO 1055 exerts hot flash reducing effects.

PMID- 20696561
TI  - Exercise but not mannitol provocation increases urinary Clara cell protein (CC16)
      in elite swimmers.
AB  - Elite swimmers have an increased risk of developing asthma, and exposure to
      chloramine is believed to be an important trigger factor. The aim of the present
      study was to explore pathophysiological mechanisms behind induced
      bronchoconstriction in swimmers exposed to chloramine, before and after swim
      exercise provocation as well as mannitol provocation. Urinary Clara cell protein
      (CC16) was used as a possible marker for epithelial stress. 101 elite aspiring
      swim athletes were investigated and urinary samples were collected before and 1 h
      after completed exercise and mannitol challenge. CC16, 11beta-prostaglandin
      (PG)F(2alpha) and leukotriene E(4) (LTE(4)) were measured. Urinary levels of CC16
      were clearly increased after exercise challenge, while no reaction was seen after
      mannitol challenge. Similar to CC16, the level of 11beta-PGF(2alpha) was
      increased after exercise challenge, but not after mannitol challenge, while
      LTE(4) was reduced after exercise. There was no significant difference in urinary
      response between those with a negative compared to positive challenge, but a
      tendency of increased baseline levels of 11beta-PGF(2alpha) and LTE(4) in
      individuals with a positive mannitol challenge. The uniform increase of CC16
      after swim exercise indicates that CC16 is of importance in epithelial stress,
      and may as such be an important pathogenic factor behind asthma development in
      swimmers. The changes seen in urinary levels of 11beta-PGF(2alpha) and LTE(4)
      indicate a pathophysiological role in both mannitol and exercise challenge.

PMID- 20696562
TI  - Optimising reverse logistics network to support policy-making in the case of
      Electrical and Electronic Equipment.
AB  - Due to the rapid growth of Waste Electrical and Electronic Equipment (WEEE)
      volumes, as well as the hazardousness of obsolete electr(on)ic goods, this type
      of waste is now recognised as a priority stream in the developed countries.
      Policy-making related to the development of the necessary infrastructure and the
      coordination of all relevant stakeholders is crucial for the efficient management
      and viability of individually collected waste. This paper presents a decision
      support tool for policy-makers and regulators to optimise electr(on)ic products'
      reverse logistics network. To that effect, a Mixed Integer Linear Programming
      mathematical model is formulated taking into account existing infrastructure of
      collection points and recycling facilities. The applicability of the developed
      model is demonstrated employing a real-world case study for the Region of Central
      Macedonia, Greece. The paper concludes with presenting relevant obtained
      managerial insights.

PMID- 20696563
TI  - Improvement of electrical properties via glucose oxidase-immobilization by
      actively turning over glucose for an enzyme-based biofuel cell modified with DNA
      wrapped single walled nanotubes.
AB  - One of the major areas of study associated with enzyme fuel cells (EFCs) has been
      identification of redox enzymes with high electron transfer rates that lead to a
      high power output. The effects of a method of enzyme immobilization by actively
      turning over glucose on the electrical properties of a fuel cell were evaluated
      under ambient conditions in attempt to increase the power of an EFC modified with
      DNA-wrapped single walled carbon nanotubes (SWNTs). The anode cyclic voltammetry
      (CV cycle) electrical properties increased as a result of glucose oxidase (GOD)
      immobilization by actively turning over glucose. Furthermore, an EFC that
      employed DNA-wrapped SWNTs and GOD immobilization in conjunction with protection
      of the active site increased the stability of the cell, which enabled maintenance
      of a high level of power production (ca. 730-760 MUW cm(-2)) for 1 week.

PMID- 20696564
TI  - Ultrasound decreases the failed labor epidural rate in resident trainees.
AB  - BACKGROUND: Epidural analgesia is widely used for pain relief during labor. The
      purpose of this study was to determine if ultrasound measurement of the depth
      from skin to epidural space before the epidural technique decreases the failure
      rate of labor analgesia. A secondary objective was to correlate ultrasound depth
      to the epidural space with actual depth of the needle at placement. METHODS: In
      this prospective, randomized, non-blinded study, 370 parturients requesting labor
      epidural analgesia were randomized to receive their epidural technique by first
      year anesthesia residents with or without prior ultrasound determination of
      epidural space depth. Outcome variables included the incidence of epidural
      catheter replacement for failed analgesia and the number of epidural attempts and
      accidental dural punctures. RESULTS: The ultrasound group had fewer epidural
      catheter replacements (P<0.02), and epidural placement attempts (P<0.01) compared
      to the control group. Pearson's correlation coefficients comparing the actual
      versus ultrasound estimated depth to the epidural space in the longitudinal
      median and transverse planes were 0.914 and 0.909, respectively. Pearson's
      correlation coefficient comparing the ultrasound estimated depths to the epidural
      space in the transverse and longitudinal median planes was 0.940. No significant
      differences were noted with respect to staff interventions, top-ups, accidental
      dural punctures, and delivery outcome. CONCLUSIONS: Ultrasound measurement of the
      epidural space depth before epidural technique placement decreases the rate of
      epidural catheter replacements for failed labor analgesia, and reduces the number
      of epidural attempts when performed by first year residents and compared to
      attempts without ultrasound guidance.

PMID- 20696565
TI  - Poly-chlorinated dibenzo-p-dioxins, dibenzo-furans and dioxin-like poly
      chlorinated biphenyls occurrence and removal in conventional and membrane
      activated sludge processes.
AB  - The paper presents the results of a study focused on the occurrence and removal
      of dioxins and furans (PCDD/F) and poly-chlorinated biphenyls (PCB) in both
      conventional and membrane wastewater treatment processes. It was found that the
      conventionally activated sludge process could perform a good removal of PCDDs/Fs
      and PCBs, but the relatively low solid retention time applied and the presence of
      suspended solids in the effluent limited the removal capability of the system. On
      the other hand, the membrane bioreactor was capable of perfectly removing
      PCDDs/Fs and PCBs giving an effluent characterised by concentrations under the
      limit of detection for most of the tested compounds. This efficiency was the
      result of both the solids removal from the effluent (permeate) and the
      application of prolonged solid retention times which enabled the bioconversion of
      those compounds as demonstrated by the mass balances. A mathematical model was
      developed to predict the final fate of a given molecule according to the
      operational conditions applied in the wastewater treatment process.

PMID- 20696566
TI  - Production of hydrocarbon fuels from pyrolysis of soybean oils using a basic
      catalyst.
AB  - Triglycerides obtained from animals and plants have attracted great attention
      from researchers for developing an environmental friendly and high-quality fuel,
      free of nitrogen and sulfur. In the present work, the production of biofuel by
      catalytic cracking of soybean oil over a basic catalyst in a continuous pyrolysis
      reactor at atmospheric pressure has been studied. Experiments were designed to
      study the effect of different types of catalysts on the yield and acid value of
      the diesel and gasoline fractions from the pyrolytic oil. It was found that basic
      catalyst gave a product with relatively low acid number. These pyrolytic oils
      were also further reacted with alcohol in order to decrease their acid value.
      After esterification, the physico-chemical properties of these biofuels were
      characterized, and compared with Chinese specifications for conventional diesel
      fuels. The results showed that esterification of pyrolytic oil from triglycerides
      represents an alternative technique for producing biofuels from soybean oils with
      characteristics similar to those of petroleum fuels.

PMID- 20696567
TI  - Chemical and microbial changes during autothermal thermophilic aerobic digestion
      (ATAD) of sewage sludge.
AB  - Autothermal thermophilic aerobic digestion (ATAD) is a promising process for
      sewage sludge stabilization. Batch experiments were conducted on sewage sludge
      collected from a municipal wastewater treatment plant in Shanghai, China, to
      evaluate the effectiveness of the ATAD system by determining changes in volatile
      suspended solids (VSSs) and to study its microbial diversity by denaturing
      gradient gel electrophoresis of 16S rRNA gene sequences amplified by PCR. The
      digestion system achieved rapid degradation of the organic substrate at 55
      degrees C. The VSS was removed by up to 45.3% and 50.4% at 216 h and 264 h,
      respectively, while NH(4)(+)-N, chemical oxidation demand and total organic
      carbon of supernatant as well as total nitrogen did not exhibit obvious declines
      after 168 h. The microbial diversity changed during the thermophilic process as
      thermophiles belonging to the Hydrogenophilaceae, Thermotogaceae, Clostridiaceae
      and the genus Ureibacillus replaced less temperature-tolerant microorganisms such
      as Sphingobacteriaceae and the genus Trichococcus.

PMID- 20696568
TI  - Theoretical and observed biogas production from plant biomass of different fibre
      contents.
AB  - The methane productivity of silage of four crop species -Zeamays L.,
      Sorghumsaccharatum, Miscanthusxgiganteus and Miscanthussacchariflorus - was
      investigated. The experiments revealed that at a hydraulic retention time of
      60days the volumetric methane yields from the Z.mays L. or S.saccharatum silages
      were higher than those from the Miscanthusxgiganteus or M.sacchariflorus silages
      because of the higher crude fibre content in Miscanthus spp. However, at
      comparable lignin concentrations in the feedstock, methane productivity for
      M.sacchariflorus (0.19+/-0.08L/g volatile solids) was twice that of
      Miscanthusxgiganteus (0.10+/-0.03L/g volatile solids). The efficiency of
      cellulose conversion varied from 83.6% (S. saccharatum) to 52.1%
      (Miscanthusxgiganteus), and hemicellulose from 88.9% (Z. mays L.) to 59.7%
      (Miscanthusxgiganteus). Conversion of cellulose and hemicellulose depended on the
      ratio of these polysaccharides to the lignin concentration of the feedstock.

PMID- 20696569
TI  - Characterization and spatial distribution of bacterial communities within
      passively aerated cattle manure composting piles.
AB  - The bacterial communities in the core, bottom, top, middle-surface, and lower
      surface full-scale passively aerated cattle manure compost was investigated using
      DGGE of PCR-amplified 16S rRNA sequences. Some Bacillus species and strictly
      anaerobic thermophilic Clostridium species were dominant only in the core and
      bottom zones. In contrast, bands belonging to mesophilic bacteria such as
      Bacteroidetes, Clostoridia,alpha and gamma-proteobacteria were detected in
      surface zones, even in the initial thermophilic stage of the process. Our results
      clearly show the spatial distribution of the microbial community within full
      scale composting piles, which indicates N or C conversion by zone-specific
      bacterial communities were occurring in each zone of the pile.

PMID- 20696570
TI  - Arsenic resistance operon structure in Leptospirillum ferriphilum and proteomic
      response to arsenic stress.
AB  - The response of Leptospirillum ferriphilum ML-04 to arsenic stress was analyzed
      using two-dimensional electrophoresis (2-DE), matrix-assisted laser desorption
      ionization time of flight mass spectrometry (MALDI-TOF MS). Thirty-eight of 65
      significantly differentially expressed arsenic response proteins were identified,
      and 25 of them have known functions. Three proteins are arsenic resistance system
      (ARS) member proteins. Two ars operons appear to be present in this strain. In
      addition to the ARS system, phosphate regulation and glutathione (GSH) synthesis
      appear involved in As[V] and As[III] tolerance, respectively. These findings
      provide information potentially useful for the genetic engineering of arsenic
      resistant organisms.

PMID- 20696571
TI  - Feasibility of incorporating cotton seed extract in Clostridium strain P11
      fermentation medium during synthesis gas fermentation.
AB  - Biomass gasification followed by fermentation of syngas to ethanol is a potential
      process to produce bioenergy. To make this process more economical, the
      complexity of media should be reduced while using less costly components. In this
      study, the feasibility of incorporating cotton seed extract (CSE) as a media
      component for syngas fermentation to produce ethanol using Clostridium strain P11
      was evaluated. A factorial experiment was conducted to screen and evaluate the
      effect of different media components, in relation to CSE, on ethanol production.
      Also, different CSE concentrations as well as the presence of MES buffer were
      tested to determine their effect on ethanol production. Bottle fermentations with
      media containing only 1.0 gL(-1) CSE produced more ethanol after 15 d (1.17 gL(
      1)) than fermentation using any other media. Further bottle experiments showed
      that media containing only 0.5 gL(-1) CSE produced more ethanol after 15 days
      (2.67 gL(-1)) than a control media (0.6 gL(-1)) and media containing only 1.0 gL(
      1) CSE (2.16 gL(-1)). Fermentations in 5- and 7.5-L stirred fermentors with 0.5
      gL(-1) CSE media achieved ethanol concentrations similar to those observed in
      bottle studies. These results indicate that CSE can replace all the vitamin and
      mineral media components generally used for fermentation of syngas to ethanol by
      Clostridium strain P11, thereby improving the process economics.

PMID- 20696572
TI  - Biodiesel production from waste cooking oil catalyzed by TiO2-MgO mixed oxides.
AB  - Mixed oxides of TiO(2)-MgO obtained by the sol-gel method were used to convert
      waste cooking oil into biodiesel. Titanium improved the stability of the catalyst
      because of the defects induced by the substitution of Ti ions for Mg ions in the
      magnesia lattice. The best catalyst was determined to be MT-1-923, which is
      comprised of an Mg/Ti molar ratio of 1 and calcined at 923 K, based on an
      assessment of the activity and stability of the catalyst. The main reaction
      parameters, including methanol/oil molar ratio, catalyst amount, and temperature,
      were investigated. The catalytic activity of MT-1-923 decreased slowly in the
      reuse process. After regeneration, the activity of MT-1-923 slightly increased
      compared with that of the fresh catalyst due to an increase in the specific
      surface area and average pore diameter. The mixed oxides catalyst, TiO(2)-MgO,
      showed good potential in large-scale biodiesel production from waste cooking oil.

PMID- 20696573
TI  - Investigation of nutrient feeding strategies in a countercurrent mixed-acid multi
      staged fermentation: development of segregated-nitrogen model.
AB  - The MixAlco process is a biorefinery based on the production of carboxylic acids
      via mixed-culture fermentation. Nitrogen is essential for microbial growth and
      metabolism, and may exist in soluble (e.g., ammonia) or insoluble forms (e.g.,
      cells). Understanding the dynamics of nitrogen flow in a countercurrent
      fermentation is necessary to develop control strategies to maximize performance.
      To estimate nitrogen concentration profiles in a four-stage fermentation train, a
      mass balance-based segregated-nitrogen model was developed, which uses separate
      balances for solid- and liquid-phase nitrogen with nitrogen reaction flux between
      phases assumed to be zero. Comparison of predictions with measured nitrogen
      profiles from five trains, each with a different nutrient contacting pattern,
      shows the segregated-nitrogen model captures basic behavior and is a reasonable
      tool for estimating nitrogen profiles. The segregated-nitrogen model may be used
      to (1) estimate optimal nitrogen loading patterns, (2) develop a reaction-based
      model, (3) understand influence of model inputs (e.g., operating parameters,
      feedstock properties, nutrient loading pattern) on the steady-state nitrogen
      profile, and (4) determine the direction of the nitrogen reaction flux between
      liquid and solid phases.

PMID- 20696574
TI  - Pretreatment of guayule biomass using supercritical carbon dioxide-based method.
AB  - Guayule, a desert shrub harvested for commercial production of hypoallergenic
      latex and resins constitutes <20% of the biomass. Converting the remaining
      bagasse to biorefinery feedstock for value-added products is an optimal economic
      option. A supercritical CO(2)-based process had been developed previously for
      resin extraction. In this study, the feasibility of including a supercritical
      CO(2)-based bagasse pretreatment method was evaluated. The pretreatment involved:
      adding water to the bagasse, raising system temperature, pressurizing using
      supercritical CO(2), holding the system for a period of time, and exploding the
      bagasse. The pretreated biomass was subjected to enzyme hydrolysis. The yields of
      released sugars were used as pretreatment effectiveness indicators. Supercritical
      method outperformed other methods and gave much higher overall sugar yields for
      guayule (as high as 77% for glucose and 86% for total reducing sugars through
      both pretreatment and hydrolysis, as compared to 50% for glucose and 52% for
      total sugars with the dilute-acid pretreatment and 36% for glucose and 52% for
      total sugars with the delignification pretreatment). The enzymatic hydrolyzates
      were tested on the cellulase-producing fungus Trichoderma reesei Rut C-30. No
      inhibitory/toxic effects were apparent in terms of cell growth, sugar
      consumption, and cellulase and xylanase production. The supercritical CO(2)-based
      method was found to be very promising for pretreatment of waste biomass as the
      feedstock for subsequent enzymatic hydrolysis and fermentation to produce value
      added bioproducts.

PMID- 20696575
TI  - Removal of mercury (II) from aqueous solution using papain immobilized on
      alginate bead: optimization of immobilization condition and modeling of removal
      study.
AB  - Papain having the characteristics of metal binding ability is immobilized on
      alginate bead. Design Expert Software (Version 7.1.6) uses Response Surface
      Methodology (RSM) for statistical designing of operating condition for
      immobilization of papain on alginate bead considering concentration of papain,
      concentration of sodium alginate, concentration of calcium chloride and pH as
      numeric factors and Specific Enzymatic Activity (SEA) of immobilized papain
      sample as response. Immobilization using 25.96 g/L papain, 20 g/L sodium alginate
      and 20 g/L calcium chloride at pH 7 gives the desired product as indicated by
      ANOVA (Analysis of Variance). Three parameters viz., initial concentration of
      mercury (II), amount of AIP and pH are varied in a systematic manner. Maximum
      98.88% removal of mercury (II) has been achieved within 8 min when simulated
      aqueous solution of mercury (II) with initial concentration of 10mg/L has been
      contacted with 5 g of AIP at pH 9 and at 35 degrees C in a batch contactor. A
      mathematical model has been developed and the value of equilibrium constant for
      binding of mercury (II) with AIP has been found to be 126797.3.

PMID- 20696576
TI  - Caproate formation in mixed-culture fermentative hydrogen production.
AB  - Caproate always appears during fermentative H(2) production but its formation was
      not well explained. It possibly results from the secondary fermentation of
      ethanol and acetate or butyrate by some special species like Clostridium
      kluyveri. This study attempts to elucidate caproate formation during the
      fermentation H(2) production by using C. kluyveri as an example and evaluating
      several possible pathways of caproate formation. A detailed energetic analysis of
      the empirical data of an H(2)-producing reactor demonstrated that caproate can be
      formed from two substrates, either ethanol and acetate or ethanol and butyrate.
      The analysis showed that at least 5 mol ethanol per mole reaction was essential
      to support caproate formation under the experimental condition. The analysis also
      indicated that the secondary fermentation by C. kluyveri might be another pathway
      to spontaneously produce H(2), butyrate, and acetate in addition to the butyrate
      acetate pathway. Co-production of caproate and H(2) from ethanol was
      thermodynamically feasible and contributed to at least 10-20% of total H(2)
      production in the reactor studied. It is also clarified that caproate formation
      is hydrogenogenic rather than hydrogenotrophic.

PMID- 20696577
TI  - WITHDRAWN: Synthesis and biological evaluation of some novel Pyrrolo[2, 3
      d]pyrimidine derivatives.
AB  - This article has been withdrawn at the request of the author(s) and/or 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- 20696578
TI  - PEGylated iminodiacetic acid zinc complex stabilizes cationic RNA-bearing
      nanoparticles.
AB  - Self-assembling nanoparticles comprising cationic polymers are of interest for
      the delivery of oligonucleotide-based therapeutics. Unfortunately, exposure of
      the nanoparticle cationic surface to plasma and plasma proteins compromises
      particle stability and circulating half-life. Herein, we report that improved
      nanoparticle stability can be achieved through temporary grafting of PEG to the
      nanoparticle surface. Grafting is induced through zinc complexation between PEG
      IDA and the exposed polyhistidylated polylysine (H-K) cationic polymer of pre
      formed nanoparticles.

PMID- 20696579
TI  - A comparison of foot kinematics in people with normal- and flat-arched feet using
      the Oxford Foot Model.
AB  - Foot posture is thought to influence predisposition to overuse injuries of the
      lower limb. Although the mechanisms underlying this proposed relationship are
      unclear, it is thought that altered foot kinematics may play a role. Therefore,
      this study was designed to investigate differences in foot motion between people
      with normal- and flat-arched feet using the Oxford Foot Model (OFM). Foot posture
      in 19 participants was documented as normal-arched (n=10) or flat-arched (n=9)
      using a foot screening protocol incorporating measurements from weightbearing
      antero-posterior and lateral foot radiographs. Differences between the groups in
      triplanar motion of the tibia, rearfoot and forefoot during walking were
      evaluated using a three-dimensional motion analysis system incorporating a multi
      segment foot model (OFM). Participants with flat-arched feet demonstrated greater
      peak forefoot plantar-flexion (-13.7 degrees  +/- 5.6 degrees  vs -6.5 degrees 
      +/- 3.7 degrees ; p=0.004), forefoot abduction (-12.9 degrees  +/- 6.9 degrees 
      vs -1.8 degrees  +/- 6.3 degrees ; p=0.002), and rearfoot internal rotation (10.6
      degrees  +/- 7.5 degrees  vs -0.2 degrees +/- 9.9 degrees ; p=0.018) compared to
      those with normal-arched feet. Additionally, participants with flat-arched feet
      demonstrated decreased peak forefoot adduction (-7.0 degrees  +/- 9.2 degrees  vs
      5.6 degrees  +/- 7.3 degrees ; p=0.004) and a trend towards increased rearfoot
      eversion (-5.8 degrees  +/- 4.4 degrees  vs -2.5 degrees  +/- 2.6 degrees ;
      p=0.06). These findings support the notion that flat-arched feet have altered
      motion associated with greater pronation during gait; factors that may increase
      the risk of overuse injury.

PMID- 20696580
TI  - Selective inhibition of methoxyflavonoids on human CYP1B1 activity.
AB  - Cytochrome P450 (CYP) 1B1 catalyzes 17beta-estradiol (E(2)) to predominantly
      carcinogenic 4-hydroxy-E(2), whereas CYP1A1 and 1A2 convert E(2) to non
      carcinogenic 2-hydroxy-E(2). Hence, selective inhibition of CYP1B1 is recognized
      to be beneficial for the prevention of E(2) related breast cancer. In this study,
      we first evaluated the structure-property relationship of 18 major flavonoids on
      inhibiting enzymatic activity of CYP1A1, 1A2 and 1B1 by using an ethoxyresorufin
      O-deethylation assay. Flavones and flavonols indicated relatively strong
      inhibitory effects on CYP1s compared with flavanone that does not have the double
      bond between C-positions 2 and 3 on the C-ring. Flavonoids used in this study
      selectively inhibited CYP1B1 activity. In particular, methoxy types of flavones
      and flavonols such as chrysoeriol and isorhamnetin showed strong and selective
      inhibition against CYP1B1. To understand why selective inhibition was observed,
      we carried out a molecular docking analysis of these methoxyflavonoids with the 2
      3 double bond and CYP1s. The results suggested that chrysoeriol and isorhamnetin
      fit well into the active site of CYP1B1, but do not fit into the active site of
      CYP1A2 and 1A1 because of steric collisions between the methoxy substituent of
      these methoxyflavonoids and Ser-122 in CYP1A1 and Thr-124 in CYP1A2. In
      conclusion, our results demonstrate: (1) strong inhibitory effects of flavonoids
      on CYP1 activities require the 2-3 double bond on the C-ring; (2)
      methoxyflavonoids with the 2-3 double bond had strong and selective inhibition
      against CYP1B1, suggesting chemopreventive flavonoids for E(2) related breast
      cancer; and (3) binding specificity of these methoxyflavonoids is based on the
      interactions between the methoxy groups and specific CYP1s residues.

PMID- 20696581
TI  - Xanthones with neuraminidase inhibitory activity from the seedcases of Garcinia
      mangostana.
AB  - This study was designed to gain deeper insights into the molecular properties of
      natural xanthones as neuraminidase inhibitors. A series of xanthones 1-12 was
      isolated from the seedcases of Garcinia mangostana and evaluated for bacteria
      neuraminidase inhibitory activity. Compounds 11 and 12 emerged to be new
      xanthones (mangostenone F, mangostenone G) which we fully spectroscopically
      characterized. The IC(50) values of compounds 1-12 were determined to range
      between 0.27-65.7 microM. The most potent neuraminidase inhibitor 10 which has an
      IC(50) of 270 nM features a 5,8-diol moiety on the B ring. Interestingly,
      structure-activity studies reveal that these xanthones show different kinetic
      inhibition mechanisms depending upon the arrangement of hydroxyl groups in the B
      ring. Compound 6 possessing a 6,7-diol motif on the B-ring operated under the
      enzyme isomerization model (k(5)=0.1144 microM(-1) s(-1), k(6)=0.001105 s(-1),
      and K(i)(app)=7.41 microM), whereas compound 10 possessing a 5,8-diol unit
      displayed simple reversible slow-binding inhibition (k(3)=0.02294 microM(-1) s(
      1), k(4)=0.001025 s(-1), and K(i)(app)=0.04468 microM).

PMID- 20696582
TI  - The unsaturated acyclic nucleoside analogues bearing a sterically constrained (Z)
      4'-benzamido-2'-butenyl moiety: Synthesis, X-ray crystal structure study,
      cytostatic and antiviral activity evaluations.
AB  - A series of the novel acyclic unsaturated pyrimidine (1-12) and adenine (13)
      nucleoside analogues bearing conformationally restricted (Z)-2'-butenyl moiety
      were synthesized and evaluated for their antiviral and cytostatic activity
      potency against malignant tumor cell lines and normal human fibroblast (WI38).
      The N-1 and/or N-3 acyclic side chain substitution in pyrimidine ring in N-3
      substituted 5-trifluoromethyluracil derivative (11), N-1, N-3 disubstituted 5
      fluorouracil derivative (12) and adenine derivative (13) was deduced from their
      (1)H and (13)C NMR spectra and confirmed by single crystal X-ray structure
      analysis. The X-ray crystal structure analysis 11-13 revealed also supramolecular
      self-assemblies, in which infinite chains or dimers built two- and three
      dimensional networks. The results of the in vitro cytostatic activity evaluations
      of 1-13 indicate that the majority of the compounds tested exhibited a non
      specific and moderate antiproliferative effect at the highest concentration (100
      microM). Of all evaluated compounds on the cell lines tested only the N-1 4''
      fluoro-substituted-benzamide uracil derivative (7) showed rather marked and
      selective inhibitory activity against the growth of MCF-7 cells at a
      concentration of 2.7 microM and no cytotoxic effect on normal fibroblasts WI38.
      This compound can be therefore considered as a potential antitumor lead compound
      for further synthetic structure modification.

PMID- 20696583
TI  - New antitumoral agents I: In vitro anticancer activity and in vivo acute toxicity
      of synthetic 1,5-bis(4-hydroxy-3-methoxyphenyl)-1,4-pentadien-3-one and
      derivatives.
AB  - This paper describes a new method for the preparation of 1,5-bis(4-hydroxy-3
      methoxyphenyl)-1,4-pentadien-3-one 1 and its derivatives 2-5. This set of
      synthetic compounds exhibited high antitumoral activities regarding in vitro
      screening against several human tumor cell lines as lung carcinoma NCI-460,
      melanoma UACC-62, breast MCF-7, colon HT-29, renal 786-O, ovarian OVCAR-03 and
      ovarian expressing the resistance phenotype for adriamycin NCI-ADR/RES, prostate
      PC-3, and leukemia K-562. Compounds were also tested against murine tumor cell
      line B16F10 melanoma and lymphocytic leukemia L1210 as well as to their effect
      toward normal macrophages. Specific activity against colon cancer cells HT-29 was
      observed for all tested compounds and suggests further studies with models of
      colon cancer. Compounds 1, 2, and 4 showed significant cytotoxic activity with
      IC(50) values 2.3 microM for all human cancer cell lines. Intraperitoneal acute
      administration of compound 1 and 2 showed very low toxicity rate.

PMID- 20696585
TI  - Facile synthesis of peptide-porphyrin conjugates: Towards artificial catalase.
AB  - A facile synthetic method for peptide-porphyrin conjugates containing four
      peptide units on one porphyrin was developed using chemoselective reactions. The
      key building blocks, 5,10,15,20-tetrakis(3-azidophenyl)porphyrin 1 and 5,10,15,20
      tetrakis(5-azido-3-pyridyl)porphyrin 2, were efficiently synthesized and used as
      substrates for two well-known chemoselective reactions, traceless Staudinger
      ligation and copper-catalyzed azide alkyne cycloaddition (so-called click
      chemistry). Both reactions gave the desired compounds, and click chemistry was
      superior for our purpose. To confirm the value of the established methodology,
      nine peptide-porphyrin conjugates were synthesized, and their catalase- and
      peroxidase-like activity in water was evaluated. Our synthetic strategy is
      expected to be valuable for the preparation of artificial heme protein models.

PMID- 20696584
TI  - Modulation of the inhibitor properties of dipeptidyl (acyloxy)methyl ketones
      toward the CaaX proteases.
AB  - Dipeptidyl (acyloxy)methyl ketones (AOMKs) have been identified as mechanism
      based inhibitors of certain cysteine proteases. These compounds are also
      inhibitors of the integral membrane proteins Rce1p and Ste24p, which are
      proteases that independently mediate a cleavage step associated with the
      maturation of certain isoprenylated proteins. The enzymatic mechanism of Rce1p is
      ill-defined, whereas Ste24p is a zinc metalloprotease. Rce1p is required for the
      proper processing of the oncoprotein Ras and is viewed as a potential target for
      cancer therapy. In this study, we synthesized a small library of dipeptidyl AOMKs
      to investigate the structural elements that contribute to the inhibitor
      properties of this class of molecules toward Rce1p and Ste24p. The compounds were
      evaluated using a fluorescence-based in vitro proteolysis assay. The most potent
      dipeptidyl AOMKs contained an arginine residue and the identity of the benzoate
      group strongly influenced potency. A 'warhead' free AOMK inhibited Rce1p and
      Ste24p. The data suggest that the dipeptidyl AOMKs are not mechanism-based
      inhibitors of Rce1p and Ste24p and corroborate the hypothesis that Rce1p is not a
      cysteine protease.

PMID- 20696586
TI  - Mitral-valve replacement for a severely calcified mitral annulus: a simple and
      novel technique.
AB  - Systemic calcifications are often seen in patients with end-stage renal failure,
      who need long-term hemodialysis. When patients with severe calcification of the
      mitral-valve annulus undergo mitral-valve replacement (MVR), complete debridement
      of the calcified tissues may result in fatal complications such as rupture of the
      left ventricle or injury to the coronary artery. We describe a novel technique of
      MVR for a severely calcified mitral annulus and leaflet, in which only the
      anterior leaflet is excised, preserving the posterior leaflet to prevent fatal
      complications. We passed 2/0 polyester mattress sutures through the mitral
      annulus from the left ventricle to the left atrium and fixed the preserved
      posterior leaflet to the posterior mitral annulus and prosthetic valve. The
      mitral valve was replaced using a St. Jude Medical mechanical heart valve with a
      specific structure and a hinge that shifts to the left atrial side and most of
      the leaflet moves within its housing. This structure enables this procedure to be
      performed without the excision of a severely calcified posterior mitral leaflet
      and annulus. Our technique may prevent the fatal complications that can be caused
      by debridement or excision of severely calcified mitral apparatus.

PMID- 20696587
TI  - Impressive dilatation of azygos vein due to congenital anomaly of inferior vena
      cava.

PMID- 20696588
TI  - Coronary stenting for iatrogenic stenosis of the left main coronary artery post
      aortic valve replacement: an alternative treatment?
AB  - Iatrogenic coronary ostial stenosis after aortic valve replacement is a rare,
      life-threatening complication, which may follow implantation of either a
      mechanical or a biological prosthesis. Historically, this condition has been
      treated by urgent coronary bypass surgery but is associated with high morbidity
      and mortality, due to the hazards of early repeat sternotomy. We report a case of
      iatrogenic coronary ostial stenosis successfully treated with stenting and
      discuss the advantages of percutaneous intervention over coronary bypass surgery.

PMID- 20696589
TI  - Anomalous pulmonary venous connection to superior vena cava: Warden technique.
AB  - OBJECTIVE: Repair of anomalous pulmonary venous connection (APVC) to superior
      vena cava (SVC) with internal pericardial patch may be complicated by the
      obstruction of the SVC or pulmonary veins and sinus node dysfunction. Moreover,
      the shrinkage of the pericardium may lead to late obstruction. Various techniques
      are practiced, which have reduced the incidence of obstruction to the venous
      drainage, but sinus node dysfunction continues to be an issue. We reviewed our
      experience with the Warden technique, predominantly in children, for various
      types of APVC to the SVC. METHODS: Between 2006 and 2010, 32 patients with
      anomalous drainage of the pulmonary veins to SVC underwent repair by the Warden
      technique in our institute. The median age at operation was 4 years (range 3
      months-34 years). Partial anomalous pulmonary venous connection (PAPVC) was
      present in 28 patients, while four patients had total anomalous pulmonary venous
      connection (TAPVC) to the SVC, where one or more pulmonary veins joined the SVC
      separately from the entry of the common chamber. Clinical data, echocardiography
      and operative details were collected from our database, retrospectively. RESULTS:
      At a median follow-up of 24 months, there was no mortality. One patient had
      transient rhythm disturbance. On follow-up, it was revealed that all patients are
      in sinus rhythm with no evidence of systemic or pulmonary venous obstruction.
      CONCLUSION: The Warden technique is a simple and effective surgical option, which
      should be preferred for patients with anomalous drainage of the pulmonary veins
      to SVC. Though arrhythmias are rare in the early follow-up, longer follow-up is
      required to rule out their late development.

PMID- 20696590
TI  - Horizontal migration of Acartia pacifica Steuer (copepoda) in response to UV
      radiation.
AB  - It is known that zooplankton migrate vertically to avoid UV-radiation (UVR, 280
      400nm), but little is known if such avoidance happens horizontally. Here, we
      showed that the copepod Acartia pacifica avoided UV irradiated fields
      horizontally. Exposure of A. pacifica to PAR or PAR+UV-A for 30min did not make
      any difference in the horizontal distribution of the individuals. However,
      addition of UV-B radiation, that is PAR+UV-A+B, resulted in uneven distributions
      among the treatments, with significant less individuals compared to the PAR or
      PAR+UV-A treatments. More carotenoids and UV-absorbing compounds were found in
      the A. pacifica individuals that chose to stay under the radiation treatments
      with UV. It is concluded that A. pacifica can migrate horizontally to avoid UV
      related harms and those contains more protective compounds were less sensitive to
      UVR.

PMID- 20696591
TI  - Acetylation of wood causes photobleaching.
AB  - This paper deals with the photobleaching of acetylated wood. The acetylated
      spruce wood was irradiated by artificial sunlight emitted from xenon lamp with
      covering several kinds of band-pass filter. The lightness (L(*)) of acetylated
      wood increased with integral irradiance. The chroma (DeltaC(*)) decreased by
      light-irradiation with wavelength from 430nm to 500nm. However, the light
      irradiation including ultraviolet ray region made it decrease after increase with
      integral irradiance. The visible light made hue angle (h degrees ) increase,
      however, the ultraviolet ray made it decrease. The lignin degradation and the
      production of carbonyl groups were observed by light-irradiation including
      ultraviolet ray. However, no remarkable changes in IR spectra were observed by
      visible light-irradiation. Photobleaching of acetylated wood was caused by mainly
      visible light without modifying the IR spectra of lignin.

PMID- 20696592
TI  - Intrathecal chemotherapy in lymphomatous meningitis.
AB  - Central Nervous System (CNS) involvement in lymphoma can occur whether at
      diagnosis or, more often, at the progression or recurrence of disease and the
      most frequent clinical manifestation is lymphomatous meningitis (LM). The first
      risk factor for LM development is the histotype, with the highest incidence for
      highly aggressive non-Hodgkin's lymphomas (NHL) such as Burkitt's lymphoma (BL)
      and lymphoblastic lymphoma/acute lymphoblastic leukemia (LBL/ALL) and the lowest
      for indolent NHL. LM prophylaxis in aggressive NHL (other than BL and LBL/ALL) is
      a much debated question, because the identification of specific risk factors
      remains controversial. Moreover, there is not a consensus if the LM prophylaxis
      should consist of systemic chemotherapy (CT), intrathecal (i.t.) CT or both. In
      case of LM, the i.t. CT has a key role, but there is not a consensus on treatment
      schedule. Newer intensified regimens and rituximab lead to reconsider the whole
      approach to LM.

PMID- 20696593
TI  - Spatial and temporal expression of CCR3 and the common beta chain of the IL-3, IL
      5 and GM-CSF receptor in the nasal epithelium and lymphoid tissues in a rat model
      of allergic rhinitis.
AB  - BACKGROUND: Allergic rhinitis (AR) and asthma are closely related conditions that
      often co-exist, and are characterized by a Th2 inflammatory response where
      eosinophils occupy a predominant role. Strategies aimed at blocking signaling
      through the CC chemokine receptor 3 (CCR3) and/or the common beta chain of the IL
      3, IL-5 and GM-CSF receptor (betac) efficiently reduced eosinophilic inflammation
      in both animal models and in asthmatic patients. This study was therefore aimed
      at characterizing the spatio-temporal expression pattern of betac and CCR3 using
      a rat model of AR. METHODS: Sensitized rats were challenged with ovalbumin and
      sacrificed at 2h, 8h, 16h or 24h post-challenge. Nasal tissues were
      microdissected and used for mRNA quantification by QPCR, while histological
      evaluation determined the presence of eosinophils and mucosubstances. RESULTS:
      Allergen-induced recruitment of eosinophils in the distal septum and turbinates
      was maximal at 8h post-challenge, and was correlated with 2-4-fold increase in
      CCR3 and betac mRNA. Recruitment of eosinophils was also accompanied by
      upregulated IL-5, IL-4Ralpha, TNF-alpha and IFN-gamma mRNA at early time-points.
      In contrast, IL-13 and MUC5AC mRNA, as well as production of mucosubstances were
      maximal at 24h. CONCLUSIONS: betac and CCR3 could play important roles in the
      modulation of the allergic response, and their inhibition may represent a
      promising therapeutic approach for AR.

PMID- 20696594
TI  - Laser pump-probe experiments on microsecond to millisecond timescales at an
      electrostatic ion storage ring: triplet-triplet absorption by protoporphyrin-IX
      anions.
AB  - Here we demonstrate that pump-probe experiments can be carried out on microsecond
      to millisecond timescales using an electrostatic ion storage ring. As a test
      case, we have chosen protoporhyrin IX anions that have lifetimes with respect to
      dissociation after photoexcitation on this time scale. Ions were photoexcited on
      one side of the ring with either 430- or 535-nm light (pump) and then allowed to
      take a certain number of revolutions before they were photoexcited by a second
      laser pulse (probe) with wavelengths between 650 and 950 nm. If ions were first
      excited by the pump, an increased yield of neutral products caused by the
      absorption of red light was measured in a microchannel plate detector located on
      the other side of the ring. This implies that it is possible to pick out ions
      that were photoexcited by the pump pulse and to spectroscopically characterize
      these ions. We report absorption spectra of 535 nm photoexcited porphyrin anions,
      with time delays of 0.19 and 0.57 ms between the pump and probe pulses, and find
      that absorption occurs over a broad region in the red.

PMID- 20696595
TI  - A comparative study of in- and post-source decays of peptide and preformed ions
      in matrix-assisted laser desorption ionization time-of-flight mass spectrometry:
      effective temperature and matrix effect.
AB  - In-source decay (ISD) and post-source decay (PSD) of a peptide ion ([Y(6) +
      H](+)) and a preformed ion (benzyltriphenylphosphonium, BTPP) generated by matrix
      assisted laser desorption ionization (MALDI) were investigated with time-of
      flight mass spectrometry. alpha-Cyano-4-hydroxycinammic acid (CHCA) and 2,5
      dihydroxybenzoic acid (DHB) were used as matrices. For both ions, ISD yield was
      unaffected by delay time, indicating rapid termination of ISD. This was taken as
      evidence for rapid expansion cooling of hot "early" plume formed in MALDI. CHCA
      was hotter than DHB for [Y(6) + H](+) while the matrix effect was insignificant
      for BTPP. The "early" plume temperature estimated utilizing previous kinetic
      results was 800-900 K, versus 400-500 K for "late" plume. The results support our
      previous finding that the temperature of peptide ions interrogated by tandem mass
      spectrometry was lower than most rough estimates of MALDI temperature.

PMID- 20696596
TI  - Calibration function for the Orbitrap FTMS accounting for the space charge
      effect.
AB  - Ion storage in an electrostatic trap has been implemented with the introduction
      of the Orbitrap Fourier transform mass spectrometer (FTMS), which demonstrates
      performance similar to high-field ion cyclotron resonance MS. High mass spectral
      characteristics resulted in rapid acceptance of the Orbitrap FTMS for Life
      Sciences applications. The basics of Orbitrap operation are well documented;
      however, like in any ion trap MS technology, its performance is limited by
      interactions between the ion clouds. These interactions result in ion cloud
      couplings, systematic errors in measured masses, interference between ion clouds
      of different size yet with close m/z ratios, etc. In this work, we have
      characterized the space-charge effect on the measured frequency for the Orbitrap
      FTMS, looking for the possibility to achieve sub-ppm levels of mass measurement
      accuracy (MMA) for peptides in a wide range of total ion population. As a result
      of this characterization, we proposed an m/z calibration law for the Orbitrap
      FTMS that accounts for the total ion population present in the trap during a data
      acquisition event. Using this law, we were able to achieve a zero-space charge
      MMA limit of 80 ppb for the commercial Orbitrap FTMS system and sub-ppm level of
      MMA over a wide range of total ion populations with the automatic gain control
      values varying from 10 to 10(7).

PMID- 20696597
TI  - Alternative methods of normalising EMG during cycling.
AB  - We evaluated possible methods of normalisation for EMG measured during cycling.
      The MVC method, Sprint method and 70% Peak Power Output Method were investigated
      and their repeatability, reliability and sensitivity to change in workload were
      compared. Thirteen cyclists performed the same experimental protocol on three
      separate occasions. Each day, subjects firstly performed MVCs, followed by a 10s
      maximal sprint on a cycle ergometer. Subjects then performed a Peak Power Output
      (PPO) test until exhaustion. After which they cycled at 70% of PPO for 5 min at
      90 rpm. Results indicated that normalising EMG data to 70% PPO is more
      repeatable, the intra-class correlation (ICC) of 70% PPO (0.87) was significantly
      higher than for MVC (0.66) (p=0.03) and 10s sprint (0.65) (p=0.04). The 70% PPO
      method also demonstrated the least intra-subject variability for five out of the
      six muscles. The Sprint and 70% PPO method highlighted greater sensitivity to
      changes in muscle activity than the MVC method. The MVC method showed the highest
      intra-subject variability for most muscles except VM. The data suggests that
      normalising EMG to dynamic methods is the most appropriate for examining muscle
      activity during cycling over different days and for once-off measurements.

PMID- 20696598
TI  - Self, other and memory: a preface.

PMID- 20696599
TI  - Aortic and iliac fixation of seven endografts for abdominal-aortic aneurysm
      repair in an experimental model using human cadaveric aortas.
AB  - OBJECTIVE: To evaluate the proximal and distal (iliac) fixation of seven self
      expanding endografts, used in the endovascular treatment (EVAR) of abdominal
      aortic aneurysm (AAA), by measuring the displacement force (DF) necessary to
      dislocate the devices from their fixation sites. METHODS: A total of 20 human
      cadaveric aortas were exposed, left in situ and transected to serve as fixation
      zones. The Anaconda, EndoFit aorto-uni-iliac, Endurant, Powerlink, Excluder,
      Talent and Zenith stent grafts were deployed and caudal force was applied at the
      flow divider, through a force gauge. The DF needed to dislocate each device >= 20
      mm from the infrarenal neck was recorded before and after moulding-balloon
      dilatation. Cephalad force was similarly applied to each iliac limb to assess
      distal fixation before and after moulding-balloon dilatation. RESULTS: Endografts
      with fixation hooks or barbs displayed a significantly higher DF necessary to
      dislocate the proximal portion compared with devices with no such fixation
      modalities (p < 0.001). Balloon dilatation produced a significant increase in DF
      in both devices with (p < 0.001) or without (p = 0.003) hooks or barbs.
      Suprarenal support did not enhance proximal fixation (p = 0.90). Balloon
      dilatation significantly increased the DF necessary to dislodge the iliac limbs
      (p = 0.007). CONCLUSIONS: Devices with fixation hooks displayed higher proximal
      fixation. Moulding-balloon dilatation increased proximal and distal fixation.
      Suprarenal support did not affect proximal fixation.

PMID- 20696600
TI  - Comments regarding 'Assessing the Quality of Surgical Care in Vascular Surgery;
      Moving from Outcome Towards Structural and Process Measures'.

PMID- 20696601
TI  - Naturally-occurring canine herpesvirus-1 infection of the vestibular labyrinth
      and ganglion of dogs.
AB  - Although the involvement of herpesviruses in vestibular disease of humans has
      been recognised for many years, knowledge of such a link in companion animal
      species is restricted to cats. This study was conducted to assess the prevalence
      of canine herpesvirus-1 (CaHV-1) infection of the vestibular labyrinth (VL) and
      vestibular ganglion (VG) of dogs by PCR. 'Field' herpesvirus was detected in the
      VL of 17% and in the VG of 19% of 52 dogs, respectively. None of the 11 dogs with
      infected VG and/or VL exhibited signs of vestibular disease, whereas clinical
      signs in the remaining three animals were attributable to intra-cranial
      neoplasia. As reported for other species, the putative role of herpesvirus
      infection in canine vestibular disease requires further elucidation.

PMID- 20696602
TI  - Musings on feline injection site sarcomas.

PMID- 20696603
TI  - Identification of the tet(B) resistance gene in Streptococcus suis.
AB  - The tetracycline resistance gene, tet(B), has been described previously in gram
      negative bacteria. In this study tet(B) was detected in plasmid extracts from
      17/111 (15%) Streptococcus suis isolates from diseased pigs, representing the
      first report of this resistance gene in gram positive bacteria.

PMID- 20696604
TI  - Pharmacokinetics of methylphenidate after oral administration of immediate and
      sustained-release preparations in Beagle dogs.
AB  - Methylphenidate (MPH) is a drug administered either as an immediate- or sustained
      release preparation for the treatment of attention deficit hyperactivity disorder
      in humans. The aim of this study was to determine the pharmacokinetics of two
      different MPH formulations in the dog. Eight dogs were randomly assigned to two
      treatment groups using a two-part randomised, cross-over experimental design.
      Each subject received a single dose of 20 mg d,l-MPH as an immediate- (IR) or
      sustained-release (SR) tablet. Blood was collected at specific times, and the
      plasma concentrations of d,l-MPH were evaluated using high performance liquid
      chromatography. There were no adverse effects following the oral administration
      of d,l-MPH in either the IR or SR groups, apart from mild hyperkinesia which was
      observed in some of the IR group. The plasma concentration data of d,l-MPH were
      best described by a one-compartment model. There were significant differences in
      the maximum concentration (C(max)), time to C(max) (T(max)), area under the curve
      (AUC) and clearance (Cl) between the two formulations. The relative
      bioavailability of the SR formulation was 30.58+/-13.73% and, despite low drug
      plasma concentrations, the SR formulation resulted in uniform plasma
      concentrations of d,l-MPH. However, the dose rate of the SR formulation used in
      this study resulted in plasma concentrations that were below effective levels for
      clinical efficacy, so further studies are required to confirm the suitability of
      higher dose rates for clinical use.

PMID- 20696605
TI  - The impact of pulse duration on composite WATERGATE pulse.
AB  - As an effective method for solvent suppression, WATERGATE is widely used in high
      resolution NMR spectroscopy. It is usually composed of a number of pulses
      separated by constant intervals. However, theoretical and experimental analyses
      indicate that narrower bandwidth and lower intensities around the secondary
      suppression points occur in the excitation profile of the composite WATERGATE.
      The excitation profile distortion is caused by the chemical shift evolution
      during the RF pulses. The higher the ratio of pulse duration to the inter-pulse
      delay is, the severer the profile distorts. Therefore, in high magnetic fields,
      the effect will be serious when WATERGATE is applied to some biological samples
      whose resonances distribute over a wide range. As can be seen obviously by
      applying WATERGATE to detect a RNA-protein mixture sample in an 800 MHz
      spectrometer, the resonances of the imino protons were partially suppressed by
      showing decreased intensities, though the intended secondary suppression points
      were set far away from them. In this article, we proposed an optimized WATERGATE
      that could effectively compensate the chemical shift evolution during the RF
      pulses, and relieve the excitation profile distortion. The optimized experiment
      will be a good way to retain the imino signal intensities when WATERGATE is
      applied to detect the RNA samples in high magnetic field.

PMID- 20696606
TI  - Carnitine palmitoyltransferase 1A (CPT1A) P479L prevalence in live newborns in
      Yukon, Northwest Territories, and Nunavut.
AB  - Carnitine palmitoyltransferase 1A (CPT1A), encoded by the gene CPT1A, is the
      hepatic isoform of CPT1 and is a major regulatory point in long-chain fatty acid
      oxidation. CPT1A deficiency confers risk for hypoketotic hypoglycaemia, hepatic
      encephalopathy, seizures, and sudden unexpected death in infancy (SUDI). It
      remains controversial whether the CPT1A gene variant, c.1436C>T (p.P479L),
      identified in Inuit, First Nations, and Alaska Native infants, causes
      susceptibility to decompensation, in particular during times of fever and
      intercurrent illness. Although newborn screening for the P479L variant occurs in
      some jurisdictions, background knowledge about the presence of the variant in
      Canadian Aboriginal populations is lacking. In an effort to understand the
      population implications of the variant in northern Canada, overall frequencies of
      the variant were assessed. Further studies are underway to determine associated
      risk. Ethics approval was obtained from university REBs, local research
      institutes, and with consultation with territorial Aboriginal groups. Newborn
      screening blood spots from all infants born in 2006 in the three territories were
      genotyped for the p.P479L variant. p.P479L (c.1436C>T) allele frequencies in the
      three territories were 0.02, 0.08, and 0.77 in Yukon (n=325), Northwest
      Territories (n=564), and Nunavut (n=695), respectively. Homozygosity rates were
      0%, 3%, and 64%. Aboriginal status was available only in NWT, with allele
      frequencies of 0.04, 0.44, 0.00, and 0.01 for First Nations, Inuvialuit/Inuit,
      Metis, and non-Aboriginal populations. Although individual blood spots were not
      identified for Aboriginal ethnicity in Nunavut infants, ~90% of infants in
      Nunavut are born to Inuit women. The allele frequency and rate of homozygosity
      for the CPT1A P479L variant were high in Inuit and Inuvialuit who reside in
      northern coastal regions. The variant is present at a low frequency in First
      Nations populations, who reside in areas less coastal than the Inuit or
      Inuvialuit in the two western territories. The significance of the population and
      geographic distribution remains unclear, but the high population frequencies of
      the variant suggest a historically low penetrance for adverse outcomes. Further
      evidence is needed to determine if there is an increased risk for infant
      mortality and morbidity and whether newborn screening will be indicated on a
      population basis.

PMID- 20696607
TI  - Fluid dynamic simulation of rat brain vessels, geometrically reconstructed from
      MR-angiography and validated using phase contrast angiography.
AB  - The exact knowledge of the blood vessel geometry plays an important role, not
      only in clinical applications (stroke diagnosis, detection of stenosis), but also
      for deeper analysis of hemodynamic functional data, such as fMRI. Such vessel
      geometries can be obtained by different MR angiographic measurements. It is shown
      that simulations using computational fluid dynamics (CFD) can be used to validate
      the vessel geometry, automatically reconstructed from time of flight (TOF)
      angiograms or phase contrast angiography (PC-MRA) data. CFD simulations are based
      on PC-MRA data, since these data contain additionally rheological information
      (phases) besides merely amplitudes as is the case for TOF measurements. Parts of
      the rat brain vessel system are carefully modeled consisting of a main tube and
      second order branches. By analyzing velocity changes up and downstream of
      bifurcations, it is shown that CFD can be used to help detecting missing vessels
      in the TOF based reconstruction. It is demonstrated by artificially deleting a
      branch from the reconstruction and compared the flow in both resulting CFD
      simulations. Finally the simulations help to understand the effects of secondary
      branches on the flow in the main tube. The aim of this study is to compare the
      measured (PCA) flow data with the CFD simulation results, based on the vessel
      geometry gained from the PCA image using an in house reconstruction algorithm. If
      a more accurate simulation method is found and if in principal the simulation
      matches the PCA data, it might be possible to deduct that in cases where the
      measured data varies from the CFD simulation, the reconstruction is not complete,
      i.e. branches are missing or wrong branches were reconstructed.

PMID- 20696608
TI  - ?

PMID- 20696609
TI  - Changing demography of leprosy: Kuwait needs to be vigilant.
AB  - INTRODUCTION: Leprosy is an ancient, chronic, communicable disease. It is claimed
      that it has been 'eliminated' as a public health problem at the global level.
      However, sporadic new cases are increasingly being encountered, even in non
      endemic countries such as ours. A more disturbing fact is the increase in the
      number of cases in the indigenous population. OBJECTIVES: The aim of this study
      was to analyze the magnitude of the leprosy problem in the region of Farwaniya,
      in which most of the immigrants in Kuwait live, based on detection and prevalence
      rates over the last 6 years, in addition to a clinico-pathological analysis of
      the collected data. PATIENTS AND METHODS: All clinically diagnosed cases of
      leprosy seen over a period of 6 years, from January 2003 to December 2008, were
      included in the study. Socio-demographic details and clinical features were
      recorded on a proforma. The results were compared to similar previous data from
      Kuwait, and to that from other countries in the region. RESULTS: Forty-six
      patients (38 male and eight female) aged 22-48 years (average 33.6 years),
      clinically diagnosed with leprosy, were enrolled. Of the enrolled patients, 89.1%
      were expatriates, while 10.9% were Kuwaiti citizens. The majority of patients
      (n=24) were from India, followed by Bangladesh (n=6), Egypt (n=5), Pakistan
      (n=3), and Indonesia, Philippines and Sri Lanka (n=1 each). The duration of signs
      and symptoms ranged from 1 to 24 months (average 4.7 months). A total of 58.5% of
      expatriate patients developed their symptoms 2-5 years after entry into Kuwait.
      Delayed diagnosis (after 12 weeks) was observed in 70.8%. Thirty-one patients
      (67.4%) had multibacillary leprosy (borderline lepromatous n=15, borderline type
      n=7, borderline tuberculoid n=5, and lepromatous leprosy n=4), while 15 patients
      (32.6%) had the paucibacillary form of leprosy (tuberculoid type n=8, borderline
      tuberculoid n=7). The detection of lepra bacilli in tissue sections was the most
      common diagnostic tool (67.4%), while nasal smears showed positive results in
      28.3% of cases and the slit skin smear in 17.4%. CONCLUSIONS: This study shows
      that leprosy in the region of Farwaniya, Kuwait, which has predominantly been a
      disease of immigrants, has started to infect the Kuwaiti population; such cases
      may just represent the tip of the iceberg. Careful examination of immigrants on
      arrival and subsequent periodic regular check-ups are required to prevent the
      spread of the disease. Furthermore, early referral of suspected cases and
      screening of contacts, with initiation of treatment as early as possible, are
      essential to control the spread of leprosy in Kuwait.

PMID- 20696610
TI  - Association between neck muscle coactivation, pain, and strength in women with
      neck pain.
AB  - This study investigates the relationship between neck muscle coactivation, neck
      strength and perceived pain and disability in women with neck pain. Surface
      electromyography (EMG) was acquired from the sternocleidomastoid (SCM) and
      splenius capitis (SC) muscles of 13 women with chronic neck pain and 10 controls
      as they performed 1) maximal voluntary contractions (MVC) in flexion, extension
      and left and right lateral flexion, 2) ramped contractions from 0% to 50% MVC in
      flexion and extension and 3) circular contractions in the horizontal plane at 15N
      and 30N force. Higher values of EMG amplitude were observed for the SC
      (antagonist) during ramped neck flexion and for the SCM during ramped extension
      in the patient group (P<0.05). The patients displayed reduced values of
      directional specificity in the surface EMG of the SCM and SC for the circular
      contractions (P<0.05). The EMG amplitude of SC during cervical flexion was
      positively correlated with the patients' pain (R2 =0.35, P<0.05) and perceived
      disability (R2 0.53, P<0.01). An inverse correlation was evident between the
      amount of activation of SC during cervical flexion and strength (R2 =0.54,
      P<0.01). These observations indicate a relationship between alterations in
      neuromuscular control in patients with neck pain and functional consequences,
      including impaired motor performance and increased levels of perceived
      disability.

PMID- 20696611
TI  - Associative processes in intuitive judgment.
AB  - Dual-system models of reasoning attribute errors of judgment to two failures: the
      automatic operations of a 'System 1' generate a faulty intuition, which the
      controlled operations of a 'System 2' fail to detect and correct. We identify
      System 1 with the automatic operations of associative memory and draw on research
      in the priming paradigm to describe how it operates. We explain how three
      features of associative memory--associative coherence, attribute substitution and
      processing fluency--give rise to major biases of intuitive judgment. Our article
      highlights both the ability of System 1 to create complex and skilled judgments
      and the role of the system as a source of judgment errors.

PMID- 20696612
TI  - UV-visible, Raman and E.S.R. studies of gamma-irradiated NiO-doped sodium
      metaphosphate glasses.
AB  - UV-visible spectroscopic measurements of Ni-doped sodium phosphate glasses were
      carried out before and after successive gamma irradiation. The undoped glass
      reveals strong UV absorption originating from trace iron impurities. NiO-doped
      glasses show characteristic absorption bands due mainly to octahedral
      coordination of Ni(2+) ions. Gamma irradiation produces induced bands generated
      from intrinsic defects and extrinsic defects. The changes in the spectroscopic
      data are discussed in relation to the structural evolution caused by the changes
      in composition and coordination state of nickel ions. The change in the growth
      behaviour of the induced bands is related to the annihilation or approach
      saturation of these characteristic induced bands. Raman and E.S.R. spectroscopic
      measurements confirm the presence of nickel as Ni(2+) ions in octahedral state.

PMID- 20696613
TI  - Synthesis, spectroscopic and structural study of trans- and cis-(+/-)-3-phenyl-4
      (pyrrolidine-1-carbonyl)-isochroman-1-ones.
AB  - Synthesis, spectroscopic and structural study of trans- and cis-(+/-)-3-phenyl-4
      (pyrrolidine-1-carbonyl)-isochroman-1-ones is performed in order to obtain the
      correlation between the crystal structure and spectroscopic properties of both
      isomers in solid-state. The methods such as single crystal X-ray diffraction,
      conventional and linear-polarized IR-spectroscopy, UV-spectroscopy, mass
      spectrometry, 1H and 13C NMR are employed. Quantum chemical ab initio and DFT
      calculations are performed, to support the experimental data for the electronic
      structure and optical properties.

PMID- 20696614
TI  - Improvement of isopropanol production by metabolically engineered Escherichia
      coli using gas stripping.
AB  - To improve isopropanol production by metabolically engineered Escherichia coli
      strain TA76, the optimization of fermentation conditions and isopropanol removal
      by gas stripping were performed. Isopropanol is one of the simplest secondary
      alcohols, and it can be dehydrated to yield propylene, which is currently derived
      from petroleum as a monomer for making polypropylene. Initially, using a pH
      controlled fed-batch culture with the intermittent addition of glucose, strain
      TA76 produced 667 mM (40.1g/L) of isopropanol after 60 h, representing 73.2% (mol
      isopropanol/mol glucose) of the theoretical maximum yield. Because the
      accumulation of isopropanol drastically reduced production yields, a gas
      stripping recovery method was incorporated into the fed-batch culture system.
      Using this approach, strain TA76 produced 2378 mM (143 g/L) of isopropanol after
      240 h with a yield of 67.4% (mol/mol). To our knowledge, this titer represents
      the highest level of isopropanol production by E. coli to date and suggests that
      strain TA76 has a great potential for commercial fermentative isopropanol
      production.

PMID- 20696615
TI  - Validation study of 24 deepwell microtiterplates to screen libraries of strains
      in metabolic engineering.
AB  - In this study we validated the use of 24 square deepwell microtiterplates to
      screen large libraries of metabolically engineered strains by investigating the
      optimization of succinate production. Wild type E. coli MG1655 and 11 derived
      mutants were physiologically evaluated by growth in 24 deepwell MTPs and 2L
      benchtop bioreactors. Growth parameters, product yields and byproduct formation
      were determined for all mutants. The results show that similar average values and
      standard deviations for these parameters were obtained. Especially a high
      correlation was noticed for the acetate byproduct yield and the succinate
      production rate. For these parameters there was no significant difference for 8
      out of 12 strains between MTPs and 2L bioreactors. However a lower maximum growth
      rate was observed in 2L reactors as opposed to 24 deepwell plates for 9 out of 12
      mutants which could be linked to the higher amount of dead cells in the benchtop
      bioreactors (12% vs. 2% in MTPs). Finally, a cluster-based approach was used to
      select good producer strains, i.e. strains with a high succinate yield and
      succinate production rate. Bad, intermediate and good producer strains were
      clustered in the same groups for MTPs and benchtop bioreactors for 11 out of the
      12 investigated strains.

PMID- 20696616
TI  - Synovial sarcoma of the lung presenting late with compression of mediastinal
      structures and its successful resection: A case report.
AB  - Synovial sarcoma accounts for 5-14% of all soft tissue tumours. We present a case
      of 35 year-old male who presented with five months history of progressively
      increasing shortness of breath and cough. On evaluation, there was no air entry
      on the left side. CAT scan chest showed a large necrotic mass involving the
      entire left hemi-thorax. The tru-cut biopsy of this mass was done and it showed
      synovial sarcoma. The entire tumour along with the lung and the pericardium was
      removed completely. The patient had an uneventful recovery and was discharged
      home in 10 days with follow-up for adjuvant chemotherapy. Due to the rarity of
      this disease, no guidelines for the treatment are available. Main existing
      treatment includes surgery followed by either radiation, chemotherapy or both.
      Synovial sarcoma should be considered in the differentials of an adolescent or
      adult male patient presenting with a mass in the thorax.

PMID- 20696617
TI  - Low social support level is associated with non-adherence to diet at 1 year in
      the Family Intervention Trial for Heart Health (FIT Heart).
AB  - OBJECTIVE: Evaluate the relationship between low social support (SS) and
      adherence to diet in a cardiovascular disease (CVD) lifestyle intervention trial.
      DESIGN: Prospective substudy. SETTING AND PARTICIPANTS: Blood
      relatives/cohabitants of hospitalized cardiac patients in a randomized controlled
      trial (n=458; 66% female, 35% nonwhite, mean age 50 years). MAIN OUTCOME
      MEASURES: Non-adherence to diet using MEDFICTS (Meats, Eggs, Dairy, Fried foods,
      fat In baked goods, Convenience foods, fats added at the Table, and Snacks) tool;
      SS using the Enhancing Recovery in Coronary Heart Disease Patients Social Support
      Instrument. ANALYSIS: Logistic regression models adjusted for confounders.
      RESULTS: Significant predictors (P<.05) of non-adherence to diet recommendations
      at 1 year included low SS, increased body mass index and waist size, lower
      physical activity, depression, pre-action stages of change, control group
      assignment, and being male. Those with low SS at baseline 2.7 greater odds of
      being non-adherent to diet at 1 year vs those with higher SS (95% confidence
      interval=1.1-6.4); there was no interaction by group assignment. CONCLUSION AND
      IMPLICATIONS: Low SS at baseline was independently associated with non-adherence
      to diet at 1 year, suggesting that family members with low SS may be at
      heightened CVD risk as a result of poor dietary adherence.

PMID- 20696618
TI  - Extremely prolonged HIV seroconversion associated with an MHC haplotype carrying
      disease susceptibility genes for antibody deficiency disorders.
AB  - Severe immunodeficiency during primary human immunodeficiency virus (HIV)
      infection is unusual. Here, we characterized viral and immunological parameters
      in a subject presenting with Pneumocystis jirovecii pneumonia in the setting of
      prolonged primary HIV illness and delayed seroconversion. HIV antibody was only
      detected by enzyme-linked immunosorbent assay 12 months after presentation, and
      Western blot profiles remain indeterminate. Isolated virus was of R5 phenotype,
      exhibited poor viral fitness, but was otherwise unremarkable. Analysis of HIV
      antibody isotypes showed failure to mount a detectable HIV IgG response over
      nearly 2 years of infection, in particular IgG(1)- and IgG(3)-specific responses,
      despite normal responses to common infections and vaccines. Genetic analysis
      demonstrated homozygosity for part of an MHC haplotype containing susceptibility
      genes for common variable immunodeficiency (CVID) syndrome and other antibody
      deficiency disorders. Thus, a primary disorder of specific antibody production
      may explain exceptionally slow antibody development in an otherwise severe
      seroconversion illness. This highlights the need for multiparameter testing, in
      particular use of a fourth generation HIV test, for confirming HIV infection and
      underscores the importance of host factors in HIV pathogenesis.

PMID- 20696619
TI  - Development and evaluation of candidate vaccine and antitoxin against botulinum
      neurotoxin serotype F.
AB  - To produce a vaccine suitable for human use, a recombinant non His-tagged isoform
      of the Hc domain of botulinum neurotoxin serotype F (rFHc) was expressed in
      Escherichia coli and purified by sequential chromatography. The rFHc was
      evaluated as a subunit vaccine candidate in mouse model of botulism. A dose
      response was observed in both antibody titer and protective efficacy with
      increasing dosage of rFHc and number of vaccinations. These findings suggest that
      the rFHc is an effective botulism vaccine candidate. Further, we developed a new
      antitoxin against botulinum neurotoxin serotype F (BoNT/F) by purifying F(ab')(2)
      fragments from pepsin digested serum IgGs of horses inoculated with rFHc. The
      protective effect of the F(ab')(2) antitoxin against BoNT/F was determined both
      in vitro and in vivo. The results showed that the F(ab')(2) antitoxin could
      prevent botulism in mice challenged with BoNT/F and effectively delayed
      progression of paralysis from botulism in the therapeutic setting. Thus, our
      results provide valuable experimental data for this new antitoxin as a potential
      candidate for treatment of botulism caused by BoNT/F.

PMID- 20696620
TI  - Postictal language function.
AB  - Language function in the postictal state can be successfully assessed and
      provides valuable information on seizure localization and spread. Several studies
      have shown that postictal paraphasic errors and ictal speech have value for
      seizure localization. The Cincinnati method is a simple, repeatable test that
      involves presenting a single test sentence on a card and asking the patient to
      read the sentence repeatedly until it is read correctly. It increases the yield
      of detecting paraphasic errors and ictal speech, and provides a quantitative
      measure of language recovery known as the postictal language delay, defined as
      the time from the end of the EEG ictal discharge until the test sentence is read
      correctly. This language testing method has been used for all patients admitted
      to the epilepsy monitoring unit at the Cincinnati Epilepsy Center for more than
      20 years and has been shown to: (1) lateralize temporal lobe complex partial
      seizures; (2) identify when temporal lobe complex partial seizures spread to the
      dominant hemisphere; (3) identify patients with atypical language lateralization;
      (4) distinguish between temporal and frontal complex partial seizures; and (5)
      provide some insight into speech prosody changes in nondominant temporal lobe
      complex partial seizures. The method has some limitations because it requires
      vigilance of the patient and direct interaction by the technologist, and may be
      incomplete as a result of patient agitation, but has been successfully completed
      in more than 80% of patients admitted to the epilepsy monitoring unit. This
      highly cost-effective test provides important information on seizure localization
      and spread; is easily taught to technologists, nurses, and family members; and
      should be added to testing procedures in all epilepsy monitoring units.

PMID- 20696621
TI  - Hormonal alterations following seizures.
AB  - Postictal increases in prolactin (PRL), luteinizing hormone, and follicle
      stimulating hormone have been recorded in patients with both generalized tonic
      clonic and partial seizures. Elevations of PRL and luteinizing hormone were seen
      immediately and at 20 minutes after generalized tonic-clonic seizures in male and
      female patients. Usually, PRL blood levels return to normal values within 1 hour.
      Previous studies have evaluated the utility of the transient increases in PRL,
      neuron-specific enolase, and S-100 protein as markers of epileptic seizures in
      children and adults. The conclusion was that measurement of serum PRL is a
      reliable confirmatory test in the presence of a seizure, but only modestly
      effective as a screening test for suspected seizures. Temporal lobe epilepsy is
      associated with abnormalities of reproductive physiology, but the mechanisms of
      hormonal dysregulation are not clear. A direct influence of epilepsy on the
      reproductive endocrine system is suggested by acute changes in PRL and
      gonadotropin levels following generalized and partial seizures, pointing to a
      possible relationship between temporolimbic epileptiform discharges and
      particular reproductive endocrine disorders. Chronic effects of the epileptic
      state and the acute impact of seizures could alter hypothalamic function, as
      indicated by downstream pulsatile secretion of luteinizing hormone. The brain
      controls reproductive function primarily through hypothalamic regulation of
      pituitary secretion regions of the hypothalamus. These are areas that are
      involved in the regulation, production, and secretion of gonadotropin-releasing
      hormone and receive extensive direct connections from the cerebral hemispheres,
      especially from temporolimbic structures, most notably from the amygdala, that
      are commonly involved in temporal lobe epilepsy. Significant relationships have
      been uncovered through which ictal and postictal effects of seizures and epilepsy
      may influence the function of this complex neuroendocrine system.

PMID- 20696622
TI  - Gene expression and deletion analysis of mechanisms for electron transfer from
      electrodes to Geobacter sulfurreducens.
AB  - Geobacter sulfurreducens is one of the few microorganisms available in pure
      culture known to directly accept electrons from a negatively poised electrode.
      Microarray analysis was used to compare gene transcript abundance in biofilms of
      G. sulfurreducens using a graphite electrode as the sole electron donor for
      fumarate reduction compared with transcript abundance in biofilms growing on the
      same material, but not consuming current. Surprisingly, genes for putative cell
      electrode connections, such as outer-surface cytochromes and pili, which are
      highly expressed in current-producing biofilms, were not highly expressed in
      current-consuming biofilms. Microarray analysis of G. sulfurreducens gene
      transcript abundance in current-consuming biofilms versus current-producing
      biofilms gave similar results. In both comparative studies current-consuming
      biofilms had greater transcript abundance for a gene (GSU3274) encoding a
      putative monoheme, c-type cytochrome. Deletion of genes for outer-surface
      proteins previously shown to be essential for optimal electron transfer to
      electrodes had no impact on electron transfer from electrodes. Deletion of
      GSU3274 completely inhibited electron transfer from electrodes, but had no impact
      on electron transfer to electrodes. These differences in gene expression patterns
      and the impact of gene deletions suggest that the mechanisms for electron
      transfer from electrodes to G. sulfurreducens differ significantly from the
      mechanisms for electron transfer to electrodes.

PMID- 20696623
TI  - Endonuclease V-mediated deoxyinosine excision repair in vitro.
AB  - Deoxyinosine (dI) in DNA can arise from hydrolytic or nitrosative deamination of
      deoxyadenosine. It is excised in a repair pathway that is initiated by
      endonuclease V, the nfi gene product, in Escherichia coli. Repair was studied in
      vitro using M13mp18 derived heteroduplexes containing a site-specific
      deoxyinosine. Unpaired dI/G mismatch resides within the recognition site for XhoI
      restriction endonucleases, permitting evaluation of repair occurring on
      deoxyinosine-containing DNA strand. Our results show that dI lesions were
      efficiently repaired in nfi(+)E. coli extracts but the repair level was much
      reduced in nfi mutant extracts. We subjected the deoxyinosine-containing
      heteroduplex to a purified system consisting of soluble endonuclease V fusion
      protein, DNA polymerase I, and DNA ligase, along with the four deoxynucleoside
      triphosphates. Interestingly we found these three proteins alone are sufficient
      to process the dI lesion efficiently. We also found that the 3'-exonuclease
      activity of DNA polymerase I is sufficient to remove the dI lesion in this
      minimum reconstituted assay.

PMID- 20696624
TI  - An optimized and validated RP-HPLC/UV detection method for simultaneous
      determination of all-trans-retinol (vitamin A) and alpha-tocopherol (vitamin E)
      in human serum: comparison of different particulate reversed-phase HPLC columns.
AB  - A novel, simple and fast reversed-phase HPLC/UV method was developed, optimized
      for various chromatographic conditions, and validated according to international
      guidelines for simultaneous determination of all-trans-retinol and alpha
      tocopherol in human serum using retinyl acetate as internal standard in the
      concentration of 0.5 microg/ml. A liquid-phase extraction was applied to the 250
      microl of serum with n-hexane-dichloromethane mixture (70:30, v/v), in two steps,
      using ethanol-methanol mixture (95:5, v/v) for protein precipitation and BHT
      (butylated hydroxy toluene) as stabilizer for sample preparation. Both analytes
      were analyzed on Kromasil 100 C(18) column (150 mm x 4.6 mm, 5 microm), Brownlee
      analytical (Perkin Elmer) C(18) column (150 mm x 4.6 mm, 5 microm), and Supelco
      (Supelcosil) LC-18 column (150 mm x 3 mm, 3 microm), protected by a Perkin Elmer
      C(18) (30 mm x 4.6 mm, 10 microm; Norwalk, USA) pre-column guard cartridge, at
      292 nm wavelength, using methanol-water (99:1, v/v), in isocratic mode as mobile
      phase applied at flow rate of 1.5 ml/min and 1 ml/min for both 5 microm and 3
      microm columns, respectively. Complete separation of all the analytes was
      achieved in 3 and 6 min on 3 microm and 5 microm columns, respectively by
      injecting 20 microl of sample into the HPLC system by autosampler, keeping column
      oven temperature at 25 degrees C. Different particulate reversed-phase
      chromatographic columns were evaluated in order to select the best column in
      terms of sensitivity, selectivity, resolution and short run time of both the
      analytes and it was concluded that 3 microm columns are better to be used in
      clinical set up as well as in laboratories for the separation of these analytes
      in a shorter time as compared with 5 microm columns. The method was validated and
      applied for the analysis of all-trans-retinol and alpha-tocopherol in the serum
      of human volunteers.

PMID- 20696625
TI  - [Incidence of childhood cancer in the autonomous region of Castilla y Leon in
      Spain (2003-2007)].
AB  - BACKGROUND: Since 1980, childhood cancer cases have been registered in Spain in
      the National Registry of Childhood Cancer (based on hospital cases) and since
      1990, five autonomous regions have had a population based registry. There is no
      specific registry of childhood cancer in Castilla y Leon. OBJECTIVES: Our aim was
      to estimate the childhood cancer incidence in the autonomous region of Castilla y
      Leon and to assess the usefulness of the computerised diagnosis of hospital
      discharges as a source of data in a potential autonomous region population based
      registry. METHODS: We included patients younger than 15 years old who were
      diagnosed, for the first time, of cancer during the years 2003-2007. The
      information collected was obtained through the Minimum Basic Data Set (MBDS) of
      the public hospitals in the autonomous region of Castilla y Leon. RESULTS: In
      this period of 5 years (2003-2007), 220 cases of childhood cancer had been
      reported. The most frequent cancer detected was leukaemia (28.6%) followed by the
      central nervous system tumours (19.5%) and lymphoma (15.9%). The overall rate of
      childhood cancer incidence was 152.8 cases per million children. The diagnostics
      codes did not allow tumours to be classified by their histological type in 74
      cases (33.6%). CONCLUSIONS: The overall incidence by diagnostic groups of
      childhood cancer in the autonomous region of Castilla y Leon was similar to those
      reported by other national and international registries. In a Cancer registry the
      MBDS could be useful as a data source in the capture of new cases, but in a high
      percentage of cases it does not allow tumours to be classified by their
      histological type.

PMID- 20696626
TI  - [Asthmatic crisis with treatment resistant nocturnal hypercapnia].

PMID- 20696627
TI  - Free online access to D. Ralph Millard, Jr.'s books Cleft Craft and A Rhinoplasty
      Tetralogy.

PMID- 20696628
TI  - Pretrichial incision for forehead lipoma excision.

PMID- 20696629
TI  - Reliability of the Lagrange and Rigault classification system of supracondylar
      humerus extension fractures in children.
AB  - INTRODUCTION: The Lagrange and Rigault classification was designed to describe
      extension-type supracondylar fractures of the humerus. It can also help in
      treatment decision-making. HYPOTHESIS: The reliability of this classification has
      not yet been proven. The goal of this study was to assess this system's intra-
      and interobserver reliability. METHODS: One hundred supracondylar fracture
      radiographs were randomly retrieved and reviewed by five different observers on
      two occasions in a different order. The kappa index was used to calculate the
      intra- and interobserver reliability. RESULTS: Intraobserver reliability was 0.76
      and interobserver reliability was 0.69. DISCUSSION: The study shows good intra-
      and interobserver reliability. The Lagrange and Rigault classification has
      similar reliability to other supracondylar fracture classifications.

PMID- 20696630
TI  - Investigating reasons for socioeconomic inequalities in breast cancer survival in
      New Zealand.
AB  - BACKGROUND: This study investigated the role that demographic and tumour factors
      play in explaining socioeconomic inequalities in breast cancer survival. METHODS:
      Breast cancer cases notified to the New Zealand Cancer Registry (NZCR) from April
      2005 to April 2007 were followed up to April 2009. The New Zealand area-based
      deprivation index (NZDep) was used as a measure of socioeconomic position.
      Relative survival rates were estimated using sex-, deprivation- and ethnic
      specific life tables. Multiple imputation was used to impute missing data. Excess
      mortality modelling was used to estimate the contribution of demographic and
      tumour factors to inequalities in survival. RESULTS: There were 2968 breast
      cancer cases included and 433 recorded deaths. Relative survival rates at 4 years
      varied across deprivation groups. Using NZDep deciles 1-4 (least deprived) as the
      reference group, the age- and ethnicity-adjusted hazard ratio (HR) for NZDep
      deciles 7-8 was 2.03 (CI 1.36-3.04) and for NZDep deciles 9-10 was 1.93 (CI 1.28
      2.92). In the fully adjusted model there remained 50% excess mortality for the
      two most deprived groups compared to the most affluent. Variables which measured
      timely access to care (extent/size) accounted for more of the survival disparity
      than breast cancer subtype variables (ER/PR/HER2). CONCLUSION: Women from
      deprived areas in New Zealand who are diagnosed with breast cancer are less
      likely to survive as long as those from affluent areas. A substantial proportion
      of these socioeconomic disparities can be attributed to differential access to
      health care although other factors, currently unknown, are also likely to play an
      important role.

PMID- 20696631
TI  - Maraviroc in treatment-experienced patients with HIV-1 infection - experience
      from routine clinical practice.
AB  - OBJECTIVE: Few data are available about the efficacy of maraviroc (MVC) during
      routine use. We characterized indications for MVC use and the efficacy of MVC in
      clinical practice. METHODS: Thirty-two patients treated with MVC at our
      institution between 2006 and 2009 were included. Genotypic (n +/- 31) and
      phenotypic (n +/- 13) tropism analysis was performed. We determined indications
      for MVC use, characteristics of antiretroviral combination partners and treatment
      outcome. RESULTS: Complete suppression of viral replication was achieved in 78%
      after 6 months. A median increase of 124 CD4+ cells/microl after 6 months was
      observed. Concordance between phenotypic and genotypic tropism was found in 75%.
      Indications for MVC treatment included treatment failure (n +/- 15), intolerance
      to previous antiretrovirals (n +/- 6) and add-on MVC for intensification without
      changing the current regimen (n +/- 11). The add-on strategy was used in patients
      with a relatively low viremia in order to achieve complete viral load suppression
      or in situations with suppressed viral load but judged as unstable due to an
      extensive resistance pattern. Salvage drugs most frequently combined with MVC
      were darunavir (n +/- 14) and raltegravir (n +/- 14). - The genotypic assay had
      predicted CXCR4 tropism in 5 patients, using a false positive rate (FPR) of 20%.
      Lowering the FPR to 5% predicted CCR5 tropism in 4 cases, still resulting in
      sustained complete viral response under MVC use. CONCLUSIONS: MVC containing
      salvage regimens achieve relevant CD4 cell increases and high viral response
      rates. In patients with few remaining treatment options it may be justified to
      lower the FPR-cutoff to 5% when predicting the coreceptor usage. Hereby, MVC
      could still be applied in selected patients with otherwise limited treatment
      options.

PMID- 20696632
TI  - Home-based subcutaneous immunoglobulin G replacement therapy under real-life
      conditions in children and adults with antibody deficiency.
AB  - BACKGROUND: Subcutaneous immunoglobulin (SCIG) therapy is an alternative to
      intravenous immunoglobulin (IVIG) therapy. METHODS: We evaluated the efficacy and
      safety of the SCIG Vivaglobin(formerly known as Beriglobin SC) under real-life
      conditions in a post-marketing observational study in 82 patients with primary or
      secondary antibody deficiencies. Health-related quality of life (HRQoL) was
      evaluated in a subset of 30 patients previously treated with IVIG (including 11
      children <14 years) using the Short Form 36 (SF-36) for patients > or = 14 years
      of age (adults) and the Child Health Questionnaire - Parental Form 50 (CHQ-PF50)
      for children <14 years of age. Treatment preferences were assessed in adults.
      RESULTS: The mean serum immunoglobulin G (IgG) trough level during SCIG treatment
      (7.5 g/L) was higher than during previous IVIG treatment (6.6 g/L; p<0.01). The
      investigators assessed the efficacy of SCIG therapy as "excellent" in 89% of
      patients. No systemic adverse drug reactions were observed. Improvements by > or
      = 5 points were observed in 5 of 8 SF-36 subscales and in 6 of 12 CHQ-PF50
      subscales. Statistically significant improvements (p< or =0.05) were observed for
      the SF-36 subscales of bodily pain, general health perceptions, and vitality
      (adults), and for the CHQ-PF50 subscales of general health perceptions, parental
      impact - time, parental impact - emotional, and family activities (children).
      Patients preferred SCIG over IVIG therapy (92%) and home therapy over therapy at
      the clinic/physician (83%). CONCLUSION: This study confirms that therapy with
      Vivaglobin at home is effective, safe, well tolerated, and improves quality of
      life in patients with antibody deficiency.

PMID- 20696633
TI  - Incontinence, bladder neck mobility, and sphincter ruptures in primiparous women.
AB  - OBJECTIVE: To compare the function of the pelvic floor in primiparae before and
      during pregnancy with the status post partum concerning symptoms of incontinence,
      sphincter ruptures, bladder-neck mobility and the influence of the different
      modes of deliveries. METHODS: Questionnaire evaluating symptoms of urinary and
      anal incontinence in nulliparous women before and after delivery and correlating
      these symptoms with functional changes of the pelvic floor based on a careful
      gynaecologic examination as well as perineal and endoanal ultrasound. RESULTS:
      112 women were included in our study and came for the first visit, 99 women
      returned for follow-up 6 months after childbirth. Stress and flatus incontinence
      significantly increased from before pregnancy (3 and 12%) to after childbirth (21
      and 28%) in women with spontaneous delivery or vacuum extraction. No new symptoms
      occurred after c-section. There was no significant difference between the bladder
      neck position before and after delivery. The mobility of the bladder neck was
      significantly higher after vaginal delivery using a vacuum extraction compared to
      spontaneous delivery or c-section. The bladder neck in women with post partum
      urinary stress incontinence was significantly more mobile than in continent
      controls. The endoanal ultrasound detected seven occult sphincter defects without
      any correlation to symptoms of anal incontinence. CONCLUSION: Several
      statistically significant changes of the pelvic floor after delivery were
      demonstrated. Spontaneous vaginal delivery or vacuum extraction increases the
      risk for stress or anal incontinence, delivery with vacuum extraction leads to
      higher bladder neck mobility and stress incontinent women have more mobile
      bladder necks than continent women.

PMID- 20696634
TI  - Comparison of guideline recommendations with daily practice in patients with
      renal cell carcinoma.
AB  - OBJECTIVES AND AIMS: To compare guideline recommendations with daily practice
      patterns in a German patient cohort with renal cell carcinoma. PATIENTS AND
      METHODS: 81 patients with T1 oder T2 renal cell carcinoma (RCC) were included in
      this prospective single-center study. All patients were operated in a single
      institution either by open radical nephrectomy (ORN) or nephron sparing surgery
      (NSS). Patients and doctors were evaluated using a written questionnaire with a
      follow-up of 12 months. Follow-up intervals, follow-up modalities (e. g. imaging
      modalities, laboratory controls of blood and urine) and the call on psycho
      oncological support were evaluated. RESULTS: The majority of patients (72%) were
      followed up by their urologists. Follow-up examinations included abdominal
      ultrasound, urine and blood diagnostics, conventional chest x-rays, computed
      tomography (CT) of abdomen, chest or head or abdominal Magnetic Resonance Imaging
      (MRI). There were no significant differences between patients operated by ORN or
      NSS. In total, 12.5% of patients were asking for psycho-oncological support.
      CONCLUSIONS: In general, patients were followed up according to existing
      guideline recommendations. Only a small proportion of patients asked for psycho
      oncological treatment.

PMID- 20696635
TI  - No further incidence of sepsis after splenectomy for severe trauma: a multi
      institutional experience of The trauma registry of the DGU with 1,630 patients.
AB  - OBJECTIVE: Non-operative management of blunt splenic injury in adults has been
      applied increasingly at the end of the last century. Therefore, the lifelong risk
      of overwhelming post-splenectomy infection has been the major impetus for
      preservation of the spleen. However, the prevalence of posttraumatic infection
      after splenectomy in contrast to a conservative management is still unknown.
      Objective was to determine if splenectomy is an independent risk factor for the
      development of posttraumatic sepsis and multi-organ failure. METHODS: 13,433
      patients from 113 hospitals were prospective collected from 1993 to 2005.
      Patients with an injury severity score >16, no isolated head injury, primary
      admission to a trauma center and splenic injury were included. Data were
      allocated according to the operative management into 2 groups (splenectomy (I)
      and conservative managed patients (II)). RESULTS: From 1,630 patients with
      splenic injury 758 patients undergoing splenectomy compared with 872 non
      splenectomized patients. 96 (18.3%) of the patients with splenectomy and 102
      (18.5%) without splenectomy had apparent infection after operation. Additionally,
      there was no difference in mortality (24.8% versus 22.2%) in both groups. After
      massive transfusion of red blood cells (>10) non-splenectomy patients showed a
      significant increase of multi-organ failure (46% vs. 40%) and sepsis (38% vs.
      25%). CONCLUSIONS: Non-operative management leads to lower systemic infection
      rates and mortality in adult patients with moderate blunt splenic injury (grade 1
      3) and should therefore be advocated. Patients with grade 4 and 5 injury,
      patients with massive transfusion of red blood cells and unstable patients should
      be managed operatively.

PMID- 20696636
TI  - Spiritual needs of patients with chronic pain diseases and cancer - validation of
      the spiritual needs questionnaire.
AB  - PURPOSE: For many patients confronted with chronic diseases,
      spirituality/religiosity is a relevant resource to cope. While most studies on
      patients' spiritual needs refer to the care of patients at the end of life, our
      intention was to develop an instrument to measure spiritual, existential and
      psychosocial need of patients with chronic diseases. METHODS: In an anonymous
      cross-sectional survey, we applied the Spiritual Needs Questionnaire (SpNQ
      version 1.2.) to 210 patients (75% women, mean age 54 +/- 12 years) with chronic
      pain conditions (67%), cancer (28%), other chronic conditions (5%). Patients were
      recruited at the Community Hospital Herdecke, the Institute for Complementary
      Medicine (University of Bern), and at a conference of a cancer support group in
      Herten. RESULTS: Factor analysis of the 19-item instrument (Cronbach's alpha +/-
      .93) pointed to 4 factors which explain 67% of variance: Religious Needs, Need
      for Inner Peace, Existentialistic Needs (Reflection / Meaning), and Actively
      Giving. Within the main sample of patients with chronic pain and cancer, Needs
      for Inner Peace had the highest scores, followed by Self competent Attention;
      Existentialistic Needs had low scores, while the Religious Needs scores indicate
      no interest. Patients with cancer had significantly higher SpNQ scores than
      patients with chronic pain conditions. There were just some weak associations
      between Actively Giving and life satisfaction (r +/- .17; p +/- .012), and
      negatively with the symptom score (r +/- -.29; p < .0001); Need for Inner Peace
      was weakly associated with satisfaction with treatment efficacy (r +/- .24; p <
      .0001). Regression analyses reveal that the underlying disease (i.e., cancer) was
      of outstanding relevance for the patients' spiritual needs. CONCLUSION: The
      preliminary results indicate that spiritual needs are conceptually different from
      life satisfaction, and can be interpreted as the patients' longing for spiritual
      well-being. Methods how health care professionals may meet their patients'
      spiritual needs remain to be explored.

PMID- 20696637
TI  - Primary merkel cell carcinoma clinically presenting as deep oedematous mass of
      the groin.
AB  - Merkel cell carcinoma (MCC) is a relatively rare, polyomavirus associated,
      primary neuroendocrine carcinoma of the skin which is usually arising from dermal
      skin layers. However, the origin of MCC in the subcutaneous tissue is debatable.
      We report a 58-year-old female patient with an oedematous mass on her left groin
      that was firm in consistency and had no discoloration or other visible
      abnormality of the overlying skin. On histology and immunohistology the tumour
      was consistent with the diagnosis of MCC showing a predominant subcutanous growth
      pattern. Pelvic magnetic resonance tomography revealed a tumour conglomerate
      reaching from the subcutis of the left groin to the left paraaortal and
      parailiacal region indicating widespread lymphogenic metastisation. Despite
      complete medical work-up no other MCC primary could be detected. In conclusion,
      predominant subcutaneous growth pattern as well as tumour localization in the
      groin are uncommon features of MCC. MCC showing the aforementioned features may
      be associated with significant delay of diagnosis and therefore represents an
      unfavourable prognostic factor.

PMID- 20696638
TI  - Methylated APC and GSTP1 genes in serum DNA correlate with the presence of
      circulating blood tumor cells and are associated with a more aggressive and
      advanced breast cancer disease.
AB  - BACKGROUND: Tumor-related methylated DNA and circulating tumor cells (CTC) in the
      peripheral blood might be of prognostic importance in breast cancer. Thus, the
      aim of our study was to examine free methylated DNA and CTC in the blood from
      breast cancer patients and to correlate it with clinicopathological features
      known to influence prognosis. MATERIALS AND METHODS: We prospectively obtained
      serum samples from 85 patients with breast cancer and 22 healthy volunteers. Sera
      were analysed by methylation specific PCR (MethyLight PCR) for five genes:
      adenomatous polyposis coli (APC), ras association domain family protein 1A
      (RASSF1A), estrogen receptor 1 (ESR1), CDKN2A (p16) and glutathione s-transferase
      pi 1 (GSTP1). Beta actin (ACTB) served as control. In parallel matched peripheral
      blood of 63 patients was used to assay for circulating tumor cells in the
      peripheral blood by a modified immunomagnetic AdnaTest BreastCancerSelect with
      PCR detection for EPCAM, MUC1, MGB1 and SPDEF. RESULTS: A hypermethylation in the
      APC gene in 29% (25/85), in RASSF1A in 26% (22/85), in GSTP1 in 18% (14/76) and
      in ESR1 in 38% (32/85) of all breast cancer patients was detected. No
      hypermethylation of CDKN2A was found (0/25). Blood samples of patients were
      defined CTC positive by detecting the EPCAM 13% (8/63), MUC1 16% (10/63), MGB 9%
      (5/55), SPDEF 12% (7/58) and in 27% detecting one or more genes (15/55). A
      significant difference was seen in methylated APC DNA between cancer patients and
      healthy volunteers. Moreover, methylated APC, RASSF1 and CTC were significantly
      different in metastatic versus non-metastatic disease. In addition, the presence
      of methylated APC, RASSF1A and CTC correlated significantly with AJCC-staging (p
      = 0.001, p = 0.031 and 0.002, respectively). High incidences of methylations were
      found for the genes RASSF1 and ESR1 in healthy individuals (both 23% 5/22).
      Methylated GSTP1 was predominantly found in the serum of patients with large
      primaries (p = 0.023) and was highly significantly correlated with positive
      Her2/neu status (p = 0.003). Elevated serum CA15.3 was strongly correlated with
      methylated APC and CTC detection (both p = 0.000). Methylated ESR1 failed to
      exhibit significant correlations with any of the above mentioned parameters. The
      presence of CTC in peripheral blood was significantly associated with methylated
      APC (p = 0.012) and methylated GSTP1 (p = 0.001). CONCLUSION: The detection of
      methylated APC and GSTP1 DNA in serum correlated with the presence of CTC in the
      blood of breast cancer patients. Both methylated DNA and CTC correlated with a
      more aggressive tumor biology and advanced disease.

PMID- 20696639
TI  - Sorafenib after combination therapy with gemcitabine plus doxorubicine in
      patients with sarcomatoid renal cell carcinoma: a prospective evaluation.
AB  - BACKGROUND: Sarcomatoid renal cell cancer (RCC) is a distinct histological
      variant of RCC that is associated with rapid progression and a poor prognosis.
      The optimal treatment for patients with sarcomatoid RCC remains to be defined.
      Gemcitabine plus doxorubicine (GD) has shown some efficacy, however durability of
      response is limited. We carried out a prospective, open-label study to
      investigate the efficacy and safety of sorafenib in patients after GD failure in
      sarcomatoid RCC. METHODS: Fifteen patients with pure sarcomatoid RCC and
      objective progressive disease were treated with GD (gemcitabine 1500 mg/m2,
      doxorubicine 50 mg/m2 administered by weekly intravenous infusion) until
      progression of disease. Subsequently 9 patients were switched to sorafenib (400
      mg twice daily). Tumor response was measured by physical examination and
      computerized tomography scans and evaluated according to Response Evaluation
      Criteria in Solid Tumors criteria. RESULTS: Median time to progression (TTP)
      under GD was 6.6 months (range 0.8 - 8 months). During GD treatment there were no
      remissions and 6 patients died from progressive disease. Median TTP for the 9
      patients switched to sorafenib was 10.9 months (range 0.6 - 25.5 months). During
      sorafenib therapy one patient had a partial remission lasting for 3 months and 4
      patients experienced stable disease with a duration of 3 to 9 months. Four
      patients immediately progressed on sorafenib treatment but had a slower dynamic
      of tumor progression than under GD. Dosing in both treatment phases was generally
      well tolerated with manageable toxicities and no requirement for dose reduction.
      CONCLUSIONS: Chemotherapy with GD was ineffective in our patients with pure
      sarcomatoid RCC. Subsequent anti-angiogenic treatment using the multi-tyrosine
      kinase inhibitor sorafenib resulted in additional progression-free survival in 5
      of 9 patients. Further evaluation of targeted anti-angiogenic agents for the
      treatment of sarcomatoid RCC is warranted.

PMID- 20696640
TI  - TME quality in rectal cancer surgery.
AB  - BACKGROUND: The concept of total mesorectal excision has revolutionised rectal
      cancer surgery. TME reduces the rate of local recurrence and tumour associated
      mortality. However, in clinical trials only 50% of the removed rectal tumours
      have an optimal TME quality. PATIENTS: During a period of 36 months we performed
      103 rectal resections. The majority of patients (76%; 78/103) received an
      anterior resection. The remaining patients underwent either abdominoperineal
      resection (16%; 17/103), Hartmann;s procedure (6%; 6/103) or colectomy (2%;
      2/103). RESULTS: In 90% (93/103) TME quality control could be performed. 99%
      (92/93) of resected tumours had optimal TME quality. In 1% (1/93) the mesorectum
      was nearly complete. None of the removed tumours had an incomplete mesorectum. In
      98% (91/93) the circumferential resection margin was negative. Major surgical
      complications occurred in 17% (18/103). 5% (4/78) of patients with anterior
      resection had anastomotic leakage. 17% (17/103) developed wound infections.
      Mortality after elective surgery was 4% (4/95). CONCLUSION: Optimal TME quality
      results can be achieved in all stages of rectal cancer with a rate of morbidity
      and mortality comparable to the results from the literature. Future studies
      should evaluate outcome and local recurrence in accordance to the degree of TME
      quality.

PMID- 20696641
TI  - Stented ureterovesical anastomosis in renal transplantation: does it influence
      the rate of urinary tract infections?
AB  - OBJECTIVE: Our objective was to evaluate the impact of routine use of double-J
      stents on the incidence of urinary tract infection after renal transplantation.
      METHODS: We conducted a retrospective-comparative single-centre study in 310
      consecutive adult deceased donor kidney recipients transplanted from 2002 to
      2006. Patients were divided in two groups, with or without urinary stent
      implantation. To evaluate the predictive factors for UTI, donor and recipients
      pre- and post-transplantation data were analysed. Early urological complications
      and renal function within 12 months of transplantation were included as well.
      RESULTS: A total of 157 patients were enrolled to a stent (ST) and 153 patients
      to a no-stent (NST) group. The rate of urinary tract infection at three months
      was similar between the two groups (43.3% ST vs. 40.1% NST, p = 0.65). Of the
      identified pathogens Enterococcus and Escherichia coli were the most common
      species. In multivariate analysis neither age nor immunosuppressive agents, BMI
      or diabetes seemed to have influence on the rate of UTI. When compared to males,
      females had a significantly higher risk for UTI (54.0% vs. 33.5%). CONCLUSION:
      Prophylactic stenting of the ureterovesical anastomosis does not increase the
      risk of urinary tract infection in the early postoperative period.

PMID- 20696642
TI  - Association of CD69 up-regulation on CD4+ Cla+ T cells versus patch test, strip
      patch test and clinical history in nickel sensitization.
AB  - OBJECTIVE: The patch test (PT) with its modification - the strip patch test (SPT)
      - is the standard in vivo procedure to diagnose an allergic contact dermatitis
      (ACD). To date, none of the in vitro tests for the diagnosis of ACD fulfils the
      requirements of an easy, valid and reliable test. To investigate the prediction
      ability of a flow cytometric assay of CD69 up-regulation on CD4+ CLA+ T cells in
      nickel-sensitive and non-nickel-sensitive patients. METHODS: In a prospective,
      investigator-blinded, clinical study a total of 85 nickel-sensitive (n = 44;
      51.8%) and non-nickel-sensitive patients (n = 41; 48.2%) were enrolled. The
      association between CD69 up-regulation on CD4+ CLA+ T cells on the one hand and
      PT, SPT, and clinical history on the other hand was measured. Association is
      expressed with c statistic values (receiver operating characteristic analysis)
      and corresponding 95% CIs. RESULTS: The associations were c = 0.57 (95% CI: 0.42
      0.72) between CD69 up-regulation and PT, c = 0.49 (95% CI: 0.36-0.62) between
      CD69 up-regulation and SPT, and c = 0.51 (95% CI: 0.37-0.64) between CD69 up
      regulation and clinical history. CONCLUSIONS: CD69 up-regulation on CD4+ CLA+ T
      cells in vitro could not predict neither a positive PT or SPT result nor a
      positive clinical history to nickel sulfate. The combination of clinical history
      and patch testing still remains the basis for diagnosing ACD.

PMID- 20696643
TI  - Investigation of endobronchial tuberculosis diagnoses in 22 cases.
AB  - BACKGROUND: Endobronchial tuberculosis (EBTB) is a special form of pulmonary
      tuberculosis. In spite of much progress in the diagnosis of this disease in past
      years, delayed or mistaken diagnosis is still commonly seen. OBJECTIVE: The aim
      of this study is to try to find out some useful clues for the diagnosis of EBTB,
      especially the early diagnosis. METHODS: The medical records of patients with
      EBTB were analyzed retrospectively. RESULTS: The male-to-female ratio was 1:2.2
      out of 22 patients. Patients aged below 60-years-old constituted 72.7% of the
      cases. 22.7% of these patients were smokers. The male-to-female ratio of smokers
      was 4:1. 68.2% of these patients tested all showed negative result for the HIV
      test. The frequent complaints were cough, sputum, shortness of breath and fever,
      and antibiotic treatments were usually inefficacious. Multiple lobes lesion,
      exudative shadow and atelectasis were the frequent radiological findings. Acid
      fast bacilli staining for sputum smear was positive in only 13.6% of these
      patients. Tuberculin skin test was positive in 59.1% of these patients. Granular
      lesion was the most common bronchoscopic appearance in these patients.
      Histological changes showed distinctive tuberculose lesion in 72.2% of 18
      patients undergoing bronchoscopic biopsy. CONCLUSION: The diagnosis of EBTB is
      easily delayed or mistaken because of nonspecific clinical manifestations and the
      low incidence of positive acid-fast bacilli staining. A high index of awareness
      of this disease is required for diagnosis. Bronchoscopy should be performed as
      soon as possible in suspected patients, especially when patients present positive
      tuberculin skin test or no response to antibiotic treatments.

PMID- 20696644
TI  - Hemoglobin binding activity and hemoglobin-binding protein of Prevotella
      nigrescens.
AB  - Prevotella nigrescens, lacking siderophores was found to bind to the
      hemoproteins. The binding was observed also in the envelope which was prepared by
      sonication of the cell. The binding occurred in the pH-dependent manner; the
      binding was observed below neutral pHs of the incubation mixtures but only
      slightly observed in the neutral and alkaline pHs. Furthermore, hemoglobin bound
      to the envelope was dissociated at high pHs buffers. Maximum amounts of
      hemoglobin bound to 1 mg envelope was 51.2 mug. Kd for the reaction at pH 5.0 was
      2.1 x 1010 M (210 pM). From the dot blot assay, hemoglobin could bind to a
      protein solubilized from the envelope by a detergent, referred to as hemoglobin
      binding protein (HbBP), then it was purified by the sequential procedures of ion
      exchange chromatography, affinity chromatography and isoelectric focusing.
      Molecular weight and isoelectric point of the HbBP were 46 kDa and 6.1,
      respectively.

PMID- 20696646
TI  - [Typhoid fever in Lebanon: epidemiological study].
AB  - Typhoid fever is a major public health problem, especially in developing
      countries. From 2000 through 2008, the infectious disease surveillance unit at
      the Lebanese Ministry of Public Health received 6148 reports of typhoid cases. A
      case is considered positive for typhoid or paratyphoid fever when fever of at
      least 38 degrees C persists for three days, and Salmonella enterica serovar Typhi
      or Paratyphi is isolated from blood, bone marrow, or stool. Statistical analysis
      was performed with STATA v.10 software. The most cases were recorded in 2003
      (n=891), followed by 2007 (n=879), while the fewest were recorded in 2005
      (n=461). The distribution of typhoid was not homogeneous between age groups: the
      age group most affected were those aged 20-39 years, followed by those from 10-19
      years; those older than 60 years were least affected. Nor was the geographic
      distribution, by district (combining Nabatieh and the South together),
      homogeneous. The most affected individuals were in the North (n=2,192), followed
      by Bekaa (n=1,651) and Mount Lebanon (n= 1,094). Beirut was the least affected,
      with 210 cases. The results indicate that typhoid fever remains endemic in
      Lebanon and that the risk of epidemic episodes is still present.

PMID- 20696645
TI  - Multiple liver abscesses with isolation of Streptococcus intermedius related to a
      pyogenic dental infection in an immuno-competent patient.
AB  - INTRODUCTION: Streptococcus intermedius - a member of the Streptococcus anginosus
      group - is part of the normal microbial flora of the oral cavity. Despite being
      regarded as a harmless apathogenic commensal, Streptococcus intermedius has been
      described to cause abscesses in various locations of the body. CASE PRESENTATION:
      We report the clinical case and course of treatment of a 18-year-old male patient
      presenting with multiple hepatic abscesses associated with an untreated pyogenic
      dental infection. CONCLUSION: Streptococcus intermedius can cause liver abscesses
      emerging from dental infectious foci even in previously healthy patients without
      underlying innate or aquired immunodeficiency. The case illustrates the potential
      danger and underestimated risk associated with untreated dental infections.

PMID- 20696647
TI  - Engaging medical students in occupational and environmental medicine--a new
      approach.
AB  - BACKGROUND: For a number of reasons, engaging the interest of medical students in
      the discipline of occupational and environmental medicine (OEM) can be
      challenging. AIMS: To renew a curriculum in OEM within a graduate medical
      programme with an emphasis on student involvement to maximize their interest in
      the topic. METHODS: A second year student cohort of a 4 year graduate medical
      programme was surveyed as to their preferences for the content of a short course
      of OEM embedded in their medical course. The course was extensively rewritten as
      a result of the student survey, with a number of topics deleted from the old
      course and new topics added. In order to validate the content of the new course,
      local occupational physicians (OPs) were also surveyed as to their opinion of an
      appropriate curriculum in OEM for medical students. The new course was taught to
      the subsequent cohort of second year medical students. The students' ratings of
      the course pre- and post-revision were compared. RESULTS: The student
      satisfaction rates of the course significantly improved as a result of the
      changes. The content of the student-led curriculum was strikingly similar to the
      course proposed by the local OP with a few key exceptions. CONCLUSIONS: Student
      involvement in curriculum design in OEM is entirely feasible. It can result in a
      curriculum similar to that designed by expert opinion but has the advantage of
      strongly engaging student interest.

PMID- 20696648
TI  - The Management Standards Indicator Tool and the estimation of risk.
AB  - BACKGROUND: The Health & Safety Executive's (HSE) Indicator Tool offers a measure
      of exposure to psychosocial work conditions that may be linked to stress-related
      outcomes. The HSE recommends that Indicator Tool data should be used as a basis
      for discussions concerned with the identification of psychosocial work conditions
      that might warrant prioritization for intervention. However, operational
      constraints may render discussions difficult to convene and, when they do take
      place, the absence of information on harms associated with exposures can make it
      difficult to identify intervention priorities. AIMS: To examine (i) the utility
      of the Indicator Tool for the identification of a manageable number of
      psychosocial work conditions as intervention candidates and (ii) whether
      administration of a measure of stress-related outcomes alongside the Indicator
      Tool can facilitate the identification of intervention priorities. METHODS: One
      thousand and thirty-eight employees in the London region of the Her Majesty's
      Prison Service completed the Indicator Tool and a measure of psychological well
      being. Odds ratios were calculated to estimate the risk of impairment to well
      being associated with exposure to psychosocial work conditions. RESULTS: The
      Indicator Tool identified 34 psychosocial work conditions as warranting
      improvement. Intervention priority was given to those working conditions that
      were both reported to be poor by >=50% of respondents and associated with risk of
      impairment to well-being. This method allowed for the identification of four
      areas. CONCLUSIONS: Augmentation of the Indicator Tool with a measure of stress
      related outcomes and the calculation of simple risk estimation statistics can
      assist the prioritization of intervention candidates.

PMID- 20696649
TI  - A novel psychophysical method for estimating the time course of olfactory rapid
      adaptation in humans.
AB  - In this presentation, we describe a novel method for estimating the onset time
      course of psychophysical odor adaptation in human observers. The method employs
      stimulus conditions derived from an analogous stimulus paradigm in audition. To
      test this procedure, we used liquid-dilution olfactometry to estimate 2-bottle
      discrimination thresholds for brief (600 ms) presentations of vanilla odor; 17
      volunteers (14 females; ages 18-24) served as participants. The adapting odorant
      concentration for each participant was set relative to baseline threshold for the
      600-ms target alone (i.e., the same level relative to each participant's
      threshold). To characterize the adaptation-onset time course, we compared
      thresholds for targets presented simultaneously with the adapting stimulus as a
      function of the relative delay between the onset of the adapting stimulus and
      onset of the target. As predicted from the analogous auditory studies, thresholds
      for the target stimulus increased in an orderly manner with increases in
      adaptation-to-target onset delay (i.e., as the adaptation process progressively
      decreased sensitivity). Initial increases in threshold were consistently observed
      for the briefest onset delays of 50-100 ms. An onset time constant was estimated
      at 319 ms by fitting a 2-component exponential to the mean group function.
      Adaptation magnitude was dependent on the level of adapting odorant, relative to
      threshold. When thresholds were measured in one participant with a different,
      unrelated target odorant, cineole, there was no effect of the vanilla-adapting
      stimulus on threshold. The results suggest that olfactory rapid adaptation is
      measurable psychophysically within 50-200 ms after odor onset, values consistent
      with physiological measures of adaptation in olfactory receptor neurons. This
      novel stimulus paradigm offers a powerful psychophysical tool to study both odor
      adaptation and stimulus interactions at the olfactory periphery.

PMID- 20696650
TI  - A pooled analysis of extremely low-frequency magnetic fields and childhood brain
      tumors.
AB  - Pooled analyses may provide etiologic insight about associations between exposure
      and disease. In contrast to childhood leukemia, no pooled analyses of childhood
      brain tumors and exposure to extremely low-frequency magnetic fields (ELF-MFs)
      have been conducted. The authors carried out a pooled analysis based on primary
      data (1960-2001) from 10 studies of ELF-MF exposure and childhood brain tumors to
      assess whether the combined results, adjusted for potential confounding,
      indicated an association. The odds ratios for childhood brain tumors in ELF-MF
      exposure categories of 0.1-<0.2 MUT, 0.2-<0.4 MUT, and >=0.4 MUT were 0.95 (95%
      confidence interval: 0.65, 1.41), 0.70 (95% CI: 0.40, 1.22), and 1.14 (95% CI:
      0.61, 2.13), respectively, in comparison with exposure of <0.1 MUT. Other
      analyses employing alternate cutpoints, further adjustment for confounders,
      exclusion of particular studies, stratification by type of measurement or type of
      residence, and a nonparametric estimate of the exposure-response relation did not
      reveal consistent evidence of increased childhood brain tumor risk associated
      with ELF-MF exposure. These results provide little evidence for an association
      between ELF-MF exposure and childhood brain tumors.

PMID- 20696651
TI  - Pregnancy-related mortality in southern Nepal between 2001 and 2006: independent
      estimates from a prospective, population-based cohort and a direct sisterhood
      survey.
AB  - Demographic household surveys in Nepal between 1996 and 2006 indicate potentially
      large decreases in the pregnancy-related mortality ratio and raise hopes that
      Nepal may be on track to meet Millennium Development Goal 5. Between 2002 and
      2006, 23,478 pregnant women in Sarlahi District, Nepal, were followed through
      pregnancy to 42 days postpartum. The pregnancy-related mortality ratio (PRMR) was
      estimated directly, comparing deaths among women during pregnancy or within 42
      days of pregnancy termination to livebirths. In a separate household survey,
      13,319 married females reported on the pregnancy history of 28,829 sisters,
      allowing for a concurrent comparison of estimation methodologies. In the
      prospective study, there were 121 pregnancy-related deaths and 23,662 livebirths
      (PRMR = 511, 95% confidence interval: 425, 611). In the household survey,
      participants reported 396 deaths among sisters, 87 (22.0%) of which were
      pregnancy related, and 116,491 person-years of exposure (PRMR = 529, 95%
      confidence interval: 419, 638). Two independent estimates collected with
      different methods in the same geographic area over similar time periods resulted
      in similarly high estimates of mortality that are approximately twice the current
      national estimate. Access to life-saving maternal health interventions remains
      low in rural Nepal, and continued efforts are necessary to ensure equitable and
      country-wide progress toward Millennium Development Goal 5.

PMID- 20696652
TI  - Influence of life-course socioeconomic position on incident heart failure in
      blacks and whites: the Atherosclerosis Risk in Communities Study.
AB  - The influence of early-life socioeconomic position (SEP) on incident heart
      failure in blacks and whites is unknown. The authors examined the relation
      between early-life SEP and incident, hospitalized heart failure among middle-aged
      US participants (2,503 black and 8,519 white) in the Atherosclerosis Risk in
      Communities (ARIC) Study. Early-life SEP indicators assessed included parental
      education, occupation, and home ownership. From 1987 to 2004, 221 and 537
      incident heart failure events were identified in blacks and whites, respectively.
      In Cox proportional hazards regression, early-life SEP was inversely related to
      incident heart failure after adjustment for age, gender, and study center (for
      blacks, hazard ratio (HR) = 1.39, 95% confidence interval (CI): 1.00, 1.95; for
      whites, HR = 1.32, 95% CI: 1.06, 1.64). Additional adjustment for young and mid
      to-older adulthood SEP and established heart failure risk factors attenuated this
      association towards the null in both blacks and whites. Of the SEP measures, mid
      to-older adulthood SEP showed the strongest association with incident heart
      failure in both blacks (HR = 1.32, 95% CI: 0.90, 1.96) and whites (HR = 1.39, 95%
      CI: 1.11, 1.75). SEP over the life course is related to the risk of incident
      heart failure, with SEP later in adulthood having a more prominent role than
      earlier SEP.

PMID- 20696653
TI  - RNAMotifScan: automatic identification of RNA structural motifs using secondary
      structural alignment.
AB  - Recent studies have shown that RNA structural motifs play essential roles in RNA
      folding and interaction with other molecules. Computational identification and
      analysis of RNA structural motifs remains a challenging task. Existing motif
      identification methods based on 3D structure may not properly compare motifs with
      high structural variations. Other structural motif identification methods
      consider only nested canonical base-pairing structures and cannot be used to
      identify complex RNA structural motifs that often consist of various non
      canonical base pairs due to uncommon hydrogen bond interactions. In this article,
      we present a novel RNA structural alignment method for RNA structural motif
      identification, RNAMotifScan, which takes into consideration the isosteric (both
      canonical and non-canonical) base pairs and multi-pairings in RNA structural
      motifs. The utility and accuracy of RNAMotifScan is demonstrated by searching for
      kink-turn, C-loop, sarcin-ricin, reverse kink-turn and E-loop motifs against a
      23S rRNA (PDBid: 1S72), which is well characterized for the occurrences of these
      motifs. Finally, we search these motifs against the RNA structures in the entire
      Protein Data Bank and the abundances of them are estimated. RNAMotifScan is
      freely available at our supplementary website
      (http://genome.ucf.edu/RNAMotifScan).

PMID- 20696654
TI  - Spectral reflectance from a soybean canopy exposed to elevated CO2 and O3.
AB  - By affecting the physiology and structure of plant canopies, increasing
      atmospheric CO(2) and O(3) influence the capacity of agroecosystems to capture
      light and convert that light energy into biomass, ultimately affecting
      productivity and yield. The objective of this study was to determine if
      established remote sensing indices could detect the direct and interactive
      effects of elevated CO(2) and elevated O(3) on the leaf area, chlorophyll
      content, and photosynthetic capacity of a soybean canopy growing under field
      conditions. Large plots of soybean (Glycine max) were exposed to ambient air
      (~380 MUmol CO(2) mol(-1)), elevated CO(2) (~550 MUmol mol(-1)), elevated O(3)
      (1.2* ambient), and combined elevated CO(2) plus elevated O(3) at the soybean
      free air gas concentration enrichment (SoyFACE) experiment. Canopy reflectance
      was measured weekly and the following indices were calculated from reflectance
      data: near infrared/red (NIR/red), normalized difference vegetation index (NDVI),
      canopy chlorophyll content index (chl. index), and photochemical reflectance
      index (PRI). Leaf area index (LAI) also was measured weekly. NIR/red and LAI were
      linearly correlated throughout the growing season; however, NDVI and LAI were
      correlated only up to LAI values of ~3. Season-wide analysis demonstrated that
      elevated CO(2) significantly increased NIR/red, PRI, and chl. index, indicating a
      stimulation of LAI and photosynthetic carbon assimilation, as well as delayed
      senescence; however, analysis of individual dates resolved fewer statistically
      significant effects of elevated CO(2). Exposure to elevated O(3) decreased LAI
      throughout the growing season. Although NIR/red showed the same trend, the effect
      of O(3) on NIR/red was not statistically significant. Season-wide analysis showed
      significant effects of O(3) on PRI; however, analysis of individual dates
      revealed that this effect was only statistically significant on two dates.
      Elevated O(3) had minimal effects on the total canopy chlorophyll index. PRI
      appeared to be more sensitive to decreased photosynthetic capacity of the canopy
      as a whole compared with previously published single leaf gas exchange
      measurements at SoyFACE, possibly because PRI integrates the reflectance signal
      of older leaves with accumulated O(3) damage and healthy young, upper canopy
      leaves, enabling detection of significant decreases in photosynthetic carbon
      assimilation which have not been detected in previous studies which measured gas
      exchange of upper canopy leaves. When the canopy was exposed to elevated CO(2)
      and O(3) simultaneously, the deleterious effects of elevated O(3) were
      diminished. Reflectance data, while less sensitive than direct measurements of
      physiological/structural parameters, corroborate direct measurements of LAI and
      photosynthetic gas exchange made during the same season, as well as results from
      previous years at SoyFACE, demonstrating that these indices accurately represent
      structural and physiological effects of changing tropospheric chemistry on
      soybean growing in a field setting.

PMID- 20696655
TI  - Floret development of durum wheat in response to nitrogen availability.
AB  - In Mediterranean durum wheat production, nitrogen (N) fertilization may be
      important to stabilize and increase yields. Wheat yield responses to N
      fertilization are usually related to grains per m(2), which in turn is the
      consequence of processes related to floret development (floret initiation
      followed by floret death/survival) during stem elongation. The literature is
      rather scarce in terms of the relevance of floret developmental dynamics,
      determining the final number of grains in general terms and in particular
      regarding responsiveness to N. The aim of this study was to determine whether
      durum wheat responses to N under different water regimes are related to the
      dynamics of development of floret primordia to produce fertile florets. During
      the 2006-2007 and 2007-2008 growing seasons, experiments with a factorial
      combination of two N levels (0 and 100 or 250 kg N ha(-1)) and two levels of
      water availability (rainfed and irrigated) were carried out (although the water
      regime was only effective in the second season). The response of yield was
      largely a consequence of that in grain number per spike. Floret initiation was
      similar for both N levels in each experiment and water regime, for which the
      survival of a higher proportion of initiated florets was critical in the response
      of the crop. The diminished rate of floret abortion during the late part of stem
      elongation in response to N was associated with a slightly accelerated rate of
      floret development which allowed a higher proportion of the primordia initiated
      to reach the stage of fertile floret by flowering.

PMID- 20696656
TI  - Kin recognition in plants: a mysterious behaviour unsolved.

PMID- 20696658
TI  - Lessons from Australia: human papillomavirus is not a major risk factor for
      esophageal squamous cell carcinoma.

PMID- 20696659
TI  - Oxidatively damaged DNA/oxidative stress in children with celiac disease.
AB  - BACKGROUND: Because patients with celiac disease face increased risk of cancer
      and there is considerable circumstantial evidence that oxidatively damaged DNA
      may be used as a marker predictive of cancer development, we decided, for the
      first time, to characterize oxidative stress/oxidative DNA damage in celiac
      disease patients. METHODS: Two kinds of oxidatively damaged DNA biomarkers,
      namely, urinary excretion of 8-oxodG and 8-oxoGua, and the level of oxidatively
      damaged DNA in the leukocytes, as well as the level of antioxidant vitamins were
      analyzed using high-performance liquid chromatography (HPLC) and HPLC/gas
      chromatography with isotope dilution mass detection methods. These parameters
      were determined in three groups: (a) children with untreated celiac disease, (b)
      patients with celiac disease on a strict gluten-free diet, and (c) healthy
      children. RESULTS: The mean level of 8-oxodG in DNA isolated from the leukocytes
      and in the urine samples of the two groups of celiacs was significantly higher
      than in controls, irrespective of diet. There was no statistically significant
      difference in these parameters between treated and untreated celiacs. The mean
      plasma retinol and alpha-tocopherol concentration in the samples of untreated
      celiacs was significantly lower than in treated celiacs. CONCLUSION: Our results
      suggest that although diet can be partially responsible for oxidative
      stress/oxidatively damaged DNA in celiac patients, there is a factor independent
      of diet. IMPACT: It is possible that celiac disease patients may be helped by
      dietary supplementation rich in vitamin A (and E) to minimize the risk of cancer
      development.

PMID- 20696660
TI  - Mineral intake and lung cancer risk in the NIH-American Association of Retired
      Persons Diet and Health study.
AB  - BACKGROUND: Using data from a case-control study, we previously reported that low
      dietary intakes of magnesium (Mg), iron (Fe), zinc (Zn), copper (Cu), but not
      selenium (Se) and calcium (Ca), were associated with increased lung cancer risk.
      Due to dietary recall bias in case-control studies, our objective was to assess
      whether these findings hold in a prospective cohort study. METHODS: We analyzed
      data from the NIH-American Association of Retired Persons Diet and Health study
      of 482,875 subjects (288,257 men and 194,618 women) who were cancer-free and
      completed a food frequency questionnaire at enrollment between 1995 and 2003. Cox
      proportional hazards models were computed to estimate the relative risk adjusted
      for potential confounders. RESULTS: During a mean follow-up of 7 years, 7,052
      lung cancer cases were identified. For all subjects, we observed no significant
      associations between total (diet + supplement) Ca, Mg, Fe, Cu, Se, and Zn intakes
      and lung cancer risk. Total Ca intake was protective (P trend < 0.05) for current
      smokers and subjects with adenocarcinomas. Total Mg intake increased risk (P
      trend < 0.05) in men and current smokers. Total Fe intake was inversely
      associated with risk in women (P trend < 0.01). For dietary minerals, Mg
      increased risk (P trend < 0.05) in all subjects, among men and current smokers.
      Increased dietary Ca intake reduced risk in women (P trend = 0.05). Dietary Fe
      decreased risk in all subjects and among women (P trend < 0.05). Mineral intake
      from supplements did not affect lung cancer risk. CONCLUSIONS: Dietary minerals
      are risk factors for lung cancer. IMPACT: Dietary mineral consumption may
      influence lung cancer risk, but the associations differ by type of mineral and
      population subgroups.

PMID- 20696661
TI  - Use of folic acid-containing supplements after a diagnosis of colorectal cancer
      in the Colon Cancer Family Registry.
AB  - BACKGROUND: Supplement use among cancer patients is high, and folic acid intake
      in particular may adversely affect the progression of colorectal cancer. Few
      studies have evaluated the use of folic acid-containing supplements (FAS) and its
      predictors in colorectal cancer patients. OBJECTIVE: To assess the use of FAS,
      change in use, and its predictors after colorectal cancer diagnosis. DESIGN: We
      used logistic regression models to investigate predictors of FAS use and its
      initiation after colorectal cancer diagnosis in 1,092 patients recruited through
      the Colon Cancer Family Registry. RESULTS: The prevalence of FAS use was 35.4%
      before and 55.1% after colorectal cancer diagnosis (P = 0.004). Women were more
      likely than men to use FAS after diagnosis [odds ratio (OR), 1.47; 95% confidence
      interval (95% CI), 1.14-1.89], as were those consuming more fruit (P(trend) <
      0.0001) or vegetables (P(trend) = 0.001), and U.S. residents (P < 0.0001). Less
      likely to use FAS after diagnosis were nonwhite patients (OR, 0.66; 95% CI, 0.45
      0.97), current smokers (OR, 0.67; 95% CI, 0.46-0.96), and those with higher meat
      intake (P(trend) = 0.03). Predictors of FAS initiation after diagnosis were
      generally similar to those of FAS use after diagnosis, although associations with
      race and vegetable intake were weaker and those with exercise stronger.
      CONCLUSIONS: Our analysis showed substantial increases in the use of FAS after
      diagnosis with colorectal cancer, with use or initiation more likely among women,
      Caucasians, U.S. residents, and those with a health-promoting life-style. IMPACT:
      Studies of cancer prognosis that rely on prediagnostic exposure information may
      result in substantial misclassification.

PMID- 20696662
TI  - Polymorphisms at the Microseminoprotein-beta locus associated with physiologic
      variation in beta-microseminoprotein and prostate-specific antigen levels.
AB  - BACKGROUND: rs10993994, a single nucleotide polymorphism (SNP) at the genetic
      locus encoding beta-microseminoprotein (beta-MSP), is associated with both
      prostate cancer risk and levels of blood prostate-specific antigen (PSA), a
      biomarker used in prostate cancer screening. Therefore, we wished to determine
      the association between SNPs at MSMB, the gene encoding beta-MSP, and the levels
      of prostate-produced biomarkers beta-MSP, PSA, and human kallikrein 2 (hK2) in
      blood and semen. METHODS: Blood and semen from 304 healthy young Swedish men
      (ages 18-21) were assayed for beta-MSP, PSA, and hK2. SNPs around MSMB were
      genotyped from matched DNA and analyzed for quantitative association with
      biomarker levels. Empirical P values were multiple test-corrected and the
      independence of each SNP's effect was determined. RESULTS: rs10993994 was
      significantly associated with the blood and semen levels of beta-MSP (both P <
      1.0 x 10(-7)) and PSA (P = 0.00014 and P = 0.0019), and semen levels of hK2 (P =
      0.00027). Additional copies of the prostate cancer risk allele resulted in lower
      beta-MSP but higher PSA levels, and singly explained 23% and 5% of the variation
      seen in semen beta-MSP and PSA, respectively. Additional SNPs at MSMB are
      associated with beta-MSP and PSA independently of rs10993994. CONCLUSIONS: SNPs
      at MSMB correlate with physiologic variation in beta-MSP and PSA levels in the
      blood and semen of healthy young Swedish men. In particular, rs10993994 has a
      strong effect on beta-MSP levels. IMPACT: Our results suggest a mechanism by
      which rs10993994 might predispose to prostate cancer and raise the possibility
      that genetic variation might need to be considered in interpreting the levels of
      these biomarkers.

PMID- 20696663
TI  - The role of sexual behavior and human papillomavirus persistence in predicting
      repeated infections with new human papillomavirus types.
AB  - BACKGROUND: Although human papillomavirus (HPV) infections are common in young
      women, the rate of and risk for repeated new infections are not well documented.
      We examined the rate of and risks for new HPV detection in young women. METHODS:
      We used data from an ongoing study of HPV, initiated in 1990. Sexually active
      women ages 12 to 22 years were eligible. Interviews on behaviors and HPV testing
      were done at 4-month intervals; sexually transmitted infection (STI) testing was
      annual or if symptomatic. Starting with first HPV detection, time to the next
      (second) visit (event) with detection of new HPV types, and then the second event
      to time to third event was calculated. Risks were determined using Cox
      proportional hazard model. RESULTS: Sixty-nine percent of 1,125 women had a
      second event, and of those with a second event, 63% had a third event by 3 years,
      respectively. Women with HPV persistence from initial visit to second event
      [hazard ratio (HR) = 4.51 (3.78-5.37)], an STI [HR = 1.47 (1.00-2.17)], bacterial
      vaginosis [HR = 1.60 (1.07-2.39)], and number of new sex partners [HR = 1.10
      (1.05-1.15 per partner/mo)] were independent associations for HPV. Risks for
      third event were similar. CONCLUSION: This study documents the repeated nature of
      HPV infections in young women and their association with sexual risk behaviors.
      IMPACT: This finding underscores the lack of clinical utility of HPV testing in
      young women. Further studies are needed to examine host factors that lead to HPV
      acquisition and persistence.

PMID- 20696664
TI  - High-risk human papillomavirus in esophageal squamous cell carcinoma.
AB  - BACKGROUND: Although most cases of esophageal squamous cell carcinoma (ESCC) in
      western populations have been attributed to high levels of exposure to tobacco
      and alcohol, infectious agents have been postulated as possible causes,
      particularly human papillomavirus (HPV). METHODS: To explore this issue, we
      analyzed HPV DNA prevalence and HPV types together with lifestyle factors, in
      relation to tumor stage and survival in a low-incidence population. Archived
      tumor samples from a nationwide cohort of 222 ESCC patients were tested for the
      presence of HPV DNA by PCR; positive samples were sequenced to determine HPV
      type, and p16(INK4a) status was assessed by immunohistochemistry. RESULTS: Of 222
      ESCC patients, 8 tested HPV positive (prevalence, 3.6%; 95% confidence interval,
      1.1-6.1%), of which 6 were HPV-16 positive and 2 were HPV-35 positive. Four of
      the eight HPV-positive tumors overexpressed p16(INK4a). None of 55 normal
      esophageal tissue samples from healthy participants had any detectable HPV.
      Although the numbers were low, it seemed that patients with HPV-positive ESCC
      tumors were younger than those with HPV-negative tumors (mean age, 60.8 versus
      65.3 years, P = 0.18) and had higher body mass index (BMI) throughout life (mean
      current BMI of 25.1 for HPV positive, 22.2 for HPV negative, P = 0.08; mean BMI
      at 20 years of 25.8 for HPV positive, 22.1 for HPV negative, P = 0.003). We found
      no difference between patients with HPV-positive and HPV-negative tumors with
      respect to other lifestyle factors. CONCLUSIONS: These findings suggest a very
      low prevalence of HPV DNA in human ESCC. IMPACT: HPV is very unlikely to be a
      common cause of ESCC in Australia.

PMID- 20696665
TI  - Suicide rates and risk factors among Korean cancer patients, 1993-2005.
AB  - BACKGROUND: As the number of cancer survivors increases, suicide risk approaches
      that of the general population. We therefore investigated suicide rates and risk
      factors among Korean cancer patients. METHODS: We observed 816,295 cancer
      patients for 3,007,294 person-years from 1993 to 2005 through a nationwide cancer
      registry. We calculated their sex- and age-standardized mortality ratios (SMR)
      and studied suicide risk factors using rate ratios (RR) based on a log-linear
      Poisson regression model. RESULTS: Compared with the Korean general population,
      the suicide rate among cancer patients was high [SMR, 2.00; 95% confidence
      interval (95% CI), 1.91-2.08]. The rates were highest in the year following the
      cancer diagnosis (SMR, 3.45; 95% CI, 3.19-3.73) and were still elevated 5 years
      later (SMR, 1.23; 95% CI, 1.12-1.36). The clinical groups at highest risk were
      male pancreas cancer patients (SMR, 6.01; 95% CI, 4.33-8.33) and female lung
      cancer patients (SMR, 3.55; 95% CI, 2.55-4.94). The sociodemographic groups at
      highest risk were those who had no spouse versus those who were married (RR,
      1.50; 95% CI, 1.35-1.68), those who were not employed versus those who were (RR,
      1.39; 95% CI, 1.26-1.54), and those who did not have high school education versus
      those who had (RR, 1.52; 95% CI, 1.30-1.79). CONCLUSIONS: Korean cancer patients
      are at increased risk of suicide. Both clinical and sociodemographic factors play
      a role. IMPACT: There is a need for social support and suicide prevention
      strategies for cancer survivors in Korea.

PMID- 20696666
TI  - Job satisfaction in cancer prevention and control: a survey of the American
      Society of Preventive Oncology.

PMID- 20696667
TI  - Recent trends in molecular phylogenetic analysis: where to next?
AB  - The acquisition of large multilocus sequence data is providing researchers with
      an unprecedented amount of information to resolve difficult phylogenetic
      problems. With these large quantities of data comes the increasing challenge
      regarding the best methods of analysis. We review the current trends in molecular
      phylogenetic analysis, focusing specifically on the topics of multiple sequence
      alignment and methods of tree reconstruction. We suggest that traditional methods
      are inadequate for these highly heterogeneous data sets and that researchers
      employ newer more sophisticated search algorithms in their analyses. If we are to
      best extract the information present in these data sets, a sound understanding of
      basic phylogenetic principles combined with modern methodological techniques are
      necessary.

PMID- 20696668
TI  - Genetic architecture of novel traits in the hopi sunflower.
AB  - Following domestication, crop lineages typically undergo diversification either
      to adapt to disparate habitats or to fill novel agricultural roles. This process
      has produced the numerous varieties found in modern-day crop germplasm
      collections. Here, we mapped quantitative trait loci (QTLs) underlying unique
      traits in the Hopi sunflower, a primitive, Native American domesticate. These
      traits included a variety of achene (i.e., single-seeded fruit) characters as
      well as the extremely late flowering time of the Hopi sunflower. Composite
      interval mapping identified 42 QTLs underlying the 12 traits of interest.
      Although these QTLs were found on 10 of the 17 sunflower linkage groups, strong
      genetic correlations were evidenced by the clustering of QTLs across traits in
      certain genomic regions. The number of QTLs per trait ranged from 2 to 6, and the
      average QTL explained 14.7% of the variance (range: 2.5-46.9%). The apparent
      contribution of epistasis was minor, as has previously been observed for
      domestication-related traits. Unlike typical domestication-related traits in
      sunflower, the traits under consideration here exhibited a relatively simple
      genetic basis, with 2 QTL clusters being largely responsible for the unique
      characteristics of the Hopi sunflower. Based on the rarity of these traits in
      domesticated sunflower, it would appear that they evolved within the Hopi lineage
      following domestication. The simple genetic architecture of these traits may be a
      by-product of genetic constraints imposed by the genetically complex nature of
      domestication-related traits in sunflower, with the large number of domestication
      related QTLs limiting the fraction of the genome that is available for subsequent
      diversification.

PMID- 20696669
TI  - Population structures of the red fox (Vulpes vulpes) on the Hokkaido Island,
      Japan, revealed by microsatellite analysis.
AB  - In order to examine the population structures of the red fox (Vulpes vulpes) on
      the Hokkaido Island in Japan, we conducted analysis on 250 foxes from all over
      the island for 12 microsatellite loci. Assignment tests using the genotype data
      set showed that they were divided into 6 subpopulations. Of the 6, one was
      geographically isolated in the southern region and considered definitive
      subpopulation, whereas the other 5 were not. The slight differences among the
      latter 5 subpopulations were explained by the high adaptability and long
      dispersal of the red fox on the Hokkaido Island. Although there are few
      ecological data to explain the genetic differentiation of the southern
      population, we have proposed some hypotheses from the present ecological and
      geohistorical viewpoints. One convincing reason from the ecological viewpoint is
      the restriction of gene flow to southern Hokkaido from other areas due to
      geographical isolation resulting from the land shape. The other explanation is
      the geohistorical division of southern Hokkaido from other regions on the island
      during the last interglacial age, resulting in the isolation of the fox
      population.

PMID- 20696670
TI  - The Zea mays sexual compatibility gene ga2: naturally occurring alleles, their
      distribution, and role in reproductive isolation.
AB  - Major genes govern the fertilization of teosinte ovules by maize pollen. A pollen
      pistil compatibility system different from the previously described systems, Ga1
      s and Tcb1-s, was identified among maize lines introgressed with chromosome
      segments from 2 teosinte populations. The pistil barrier is dominant, and pollen
      competence is determined by genotype of the individual pollen grain. A major gene
      governing this incompatibility behaves as a strong allele of ga2, a locus
      identified previously among maize genetic stocks on the basis of transmission
      ratio distortion. Additionally, pollen simultaneously carrying both ga2 and Ga2
      was functional on Ga2 silks, which have the pistil barrier, indicating that Ga2
      conditions acceptance of the pollen grain rather than ga2 conditioning rejection
      of the pollen grain by Ga2 silks. The strong allele (Ga2-s), a weaker one such as
      reported among maize genetic stocks (Ga2-w), and an allele having only pollen
      competence (Ga2-m), or some combination of these, was found in all 13 of the
      teosinte populations sampled. Sympatric and parapatric maize landraces carried
      Ga2-m or the presumed null allele ga2, but Ga2-s or Ga2-w was not found. The
      combination of exclusively Ga2-s teosinte with ga2 maize, which could provide
      strong reproductive isolation, was not characteristic of the 5, paired
      populations tested.

PMID- 20696671
TI  - Development of an integrated couple of anthropomorphic models for dosimetric
      studies.
AB  - Numerical models and anthropomorphic phantoms are frequently used in radiation
      protection studies for dose evaluation purposes. In the present paper an
      integrated tool consisting of a plastic phantom coupled with a voxel model is
      presented. The voxel model was created from the image data set of a CT scan of
      the plastic phantom. The model was validated through a procedure that consisted
      in irradiating the plastic phantom and simulating the same irradiation conditions
      with the voxel model. The possibility of employing such couple of models in
      radiation protection studies was demonstrated calculating the organ dose
      conversion coefficients and comparing them with those evaluated with voxel models
      derived from human tomographic scans.

PMID- 20696672
TI  - Cardiac defects contribute to the pathology of spinal muscular atrophy models.
AB  - Spinal muscular atrophy (SMA) is an autosomal recessive disorder, which is the
      leading genetic cause of infantile death. SMA is the most common inherited motor
      neuron disease and occurs in approximately 1:6000 live births. The gene
      responsible for SMA is called Survival Motor Neuron-1 (SMN1). Interestingly, a
      human-specific copy gene is present on the same region of chromosome 5q, called
      SMN2. Motor neurons are the primary tissue affected in SMA. Although it is clear
      that SMA is a neurodegenerative disease, there are clinical reports that suggest
      that other tissues contribute to the overall phenotype, especially in the most
      severe forms of the disease. In severe SMA cases, a growing number of congenital
      heart defects have been identified upon autopsy. The most common defect is a
      developmental defect referred to as hypoplastic left heart. The purpose of this
      report is to determine whether cardiac tissue is altered in SMA models and
      whether this could contribute to SMA pathogenesis. Here we identified early-stage
      developmental defects in a severe model of SMA. Additionally, pathological
      responses including fibrosis and oxidative stress markers were observed shortly
      after birth in a less severe model of disease. Similarly, functional differences
      were detected between wild-type and early-stage SMA animals. Collectively, this
      work demonstrates the importance of cardiac development and function in these
      severe models of SMA.

PMID- 20696674
TI  - An exact method for link parameter estimation in error benchmarking: an
      application to Phase II two-stage single arm oncology trials.
AB  - Bayesian trial designs rely on the specification of a vague data prior to the
      determination of trial outcome. Phase II two-stage single arm oncology trials
      have a generally small sample size which may not provide the necessary amount of
      data to outweigh a misspecified or overly optimistic prior. To account for this
      issue, clinicians may wish to benchmark Bayesian errors with frequentist measures
      of trial validity, Type I and Type II errors. A confidence prior, reflecting the
      clinician's confidence in the efficacy of the treatment before data accrual, is
      used to equate the errors across design strategies. An exact method, modelling
      both the inherent small sample size and multi-stage decision process of Phase II
      single arm trials, is presented for constructing the confidence prior.

PMID- 20696673
TI  - Ancestral paternal genotype controls body weight and food intake for multiple
      generations.
AB  - Current treatments have largely failed to slow the rapidly increasing world-wide
      prevalence of obesity and its co-morbidities. Despite a strong genetic
      contribution to obesity (40-70%), only a small percentage of heritability is
      explained with current knowledge of monogenic abnormalities, common sequence
      variants and conventional modes of inheritance. Epigenetic effects are rarely
      tested in humans because of difficulties arranging studies that distinguish
      conventional and transgenerational inheritance while simultaneously controlling
      environmental factors and learned behaviors. However, growing evidence from model
      organisms implicates genetic and environmental factors in one generation that
      affect phenotypes in subsequent generations. In this report, we provide the first
      evidence for paternal transgenerational genetic effects on body weight and food
      intake. This test focused on the obesity-resistant 6C2d congenic strain, which
      carries the Obrq2a(A/J) allele on an otherwise C57BL/6J background. Various
      crosses between 6C2d and the control C57BL/6J strain showed that the Obrq2a(A/J)
      allele in the paternal or grandpaternal generation was sufficient to inhibit diet
      induced obesity and reduce food intake in the normally obesity-susceptible, high
      food intake C57BL/6J strain. These obesity-resistant and reduced food intake
      phenotypes were transmitted through the paternal lineage but not the maternal
      lineage with equal strength for at least two generations. Eliminating social
      interaction between the father and both his offspring and the pregnant dam did
      not significantly affect food intake levels, demonstrating that the phenotype is
      transmitted through the male germline rather than through social interactions.
      Persistence of these phenotypes across multiple generations raises the
      possibility that transgenerational genetic effects contribute to current
      metabolic conditions.

PMID- 20696675
TI  - Statistical issues in Primary Care.

PMID- 20696676
TI  - A randomized phase II study comparing induction or consolidation chemotherapy
      with cisplatin-docetaxel, plus radical concurrent chemoradiotherapy with
      cisplatin-docetaxel, in patients with unresectable locally advanced non-small
      cell lung cancer.
AB  - BACKGROUND: In stage III non-small-cell lung cancer (NSCLC), the role of systemic
      chemotherapy preceding or following concurrent chemo-radiotherapy (CT-RT) is
      unclear. We carried out a randomized phase II study to study the toxicity
      involved-field CT-RT with either induction or consolidation cisplatin-docetaxel
      (Taxotere). PATIENTS AND METHODS: Patients were randomly assigned to receive two
      cycles of docetaxel (D) 75 mg/m(2) on day 1 and cisplatin (C) 40 mg/m(2) on days
      1 and 2, either preceding (IND arm) or following (CON arm) concurrent CT-RT,
      where 66 Gy was delivered using involved-fields concurrent with weekly D 20
      mg/m(2) and C 20 mg/m(2). Patients at higher risk for lung toxicity (V(20) > 35%)
      crossed over to IND arm. Seventy patients were needed to exclude grade (G)3-4
      esophagitis in >25%. RESULTS: Of the 70 eligible patients, 26 were treated in IND
      and 34 CON; five with V(20) >35% switched from CON to IND. The differences in G3
      4 esophagitis observed (32/2% IND versus 21/3% CON) were not significantly
      different from the hypothesized 25% rate. Rates of G>=2 pneumonitis were similar,
      but IND arm had less G3-4 neutropenia. One-year survival was 63.2% [95%
      confidence interval (CI) 48.4% to 78.0%] and 65.5% (95% CI 48.2% to 82.8%) for
      the IND and CON arms, respectively. CONCLUSION: Both study arms merit further
      testing in patients with limited volume stage III NSCLC.

PMID- 20696677
TI  - Randomized phase II study comparing docetaxel plus cisplatin, docetaxel plus
      carboplatin, and paclitaxel plus carboplatin in patients with advanced or
      recurrent endometrial carcinoma: a Japanese Gynecologic Oncology Group study
      (JGOG2041).
AB  - BACKGROUND: The purpose of this study is to assess the efficacy and safety of
      treatment with taxane plus platinum in combination therapies for advanced or
      recurrent endometrial carcinoma. PATIENTS AND METHODS: Patients with measurable
      disease derived from histologically confirmed stage III/IV or recurrent
      endometrial carcinoma were randomly assigned to receive docetaxel plus cisplatin
      (DP), docetaxel plus carboplatin (DC), or paclitaxel plus carboplatin (TC) every
      3 weeks until disease progression or adverse events prohibited further therapy.
      Among these regimens, the study evaluated the tumor response rate as the primary
      end point as well as toxicity. RESULTS: Ninety patients were enrolled. Of them,
      88 were eligible and consequently 29, 29, and 30 patients were randomly assigned
      to DP, DC, and TC, respectively. Tumor response rates were 51.7%, 48.3%, and
      60.0% in DP, DC, and TC, respectively (P = 0.65). The following toxic effects
      were observed: grade 3/4 neutropenia in 83.3%, 90.0%, and 76.6%; febrile
      neutropenia in 10.0%, 6.7%, and 3.3%; grade 3/4 thrombocytopenia in 6.7%, 10.0%,
      and 10.0%; grade 3/4 diarrhea in 13.3%, 3.3%, and 0%, respectively; and grade 3
      neurotoxicity in 10.0% of TC. These toxicity profiles were not significantly
      different. CONCLUSION: The taxane plus platinum combination therapies could be
      candidates in further phase III trials for endometrial carcinoma.

PMID- 20696678
TI  - A phase II study of combination chemotherapy with capecitabine and cisplatin in
      patients with metastatic or recurrent squamous cell carcinoma of the head and
      neck.
AB  - BACKGROUND: The purpose of this study was to assess the efficacy and toxicity of
      capecitabine and cisplatin (XP) combination chemotherapy in patients with
      metastatic or recurrent squamous cell carcinoma of the head and neck (SCCHN).
      PATIENTS AND METHODS: The chemotherapy regimen consisted of capecitabine 1250
      mg/m(2) orally twice a day on day 1 to day 14 and cisplatin 60 mg/m(2) i.v. on
      day 1. Each cycle was repeated every 3 weeks up to a maximum of six cycles.
      RESULTS: By intent-to-treat analysis, the overall response rate was 50% [complete
      response, 0/36; partial response, 18/36; 95% confidence interval (CI) 32% to
      67%]. The median progression-free survival was 3.7 months (95% CI 2.1-5.3
      months), and the median response duration was 4.9 months. The median overall
      survival and 1-year survival rate were 10.3 months (95% CI 8.5-12.1 months) and
      43.3%, respectively. The common grade 3 or 4 nonhematologic adverse events were
      anorexia (8.8%), fatigue (4.4%), diarrhea (4.4%), stomatitis (3.6%), and the hand
      foot syndrome (1.5%). The most common grade 3 or 4 hematologic adverse event was
      neutropenia (14.6%), followed by anemia (1.5%). There was no treatment-related
      death. CONCLUSION: The XP combination regimen has antitumor activity and
      acceptable safety profile in patients with metastatic or recurrent SCCHN.

PMID- 20696679
TI  - Improved treatment strategies reduce the increased mortality risk in early RA
      patients.
AB  - OBJECTIVE: A higher mortality rate in patients with RA than in the general
      population has been reported in most series. Treatment strategies for RA have
      improved dramatically over the last decades, resulting in less inflammation and
      joint damage. We investigated whether this change in treatment corresponds to
      reversal of excess mortality by studying a large inception cohort of early RA
      patients exposed to different treatment strategies. METHODS: Six hundred and
      eighty-four RA patients included in the Leiden Early Arthritis Clinic between
      1993 and 2008 were studied. Treatment was different for three inclusion periods.
      From 1993 to 1995 patients were treated with NSAIDs and only late in their
      disease with DMARDs. From 1996 to 1998 patients were promptly treated with HCQ or
      SSZ. From 1999 to 2008 patients were immediately treated with MTX monotherapy or
      in combination with other disease-modifying drugs. Life/death status was tracked
      nationally using the civic registries. Mortality rates were compared with the
      general Dutch population. RESULTS: In Periods 1 and 2, increased standardized
      mortality rates were found, 1.35 (95% CI 0.94, 1.93) and 1.23 (95% CI 0.91,
      1.67), respectively, while a decreased standardized mortality rate was found for
      patients included in 1999-2006 [0.49 (95% CI 0.31, 0.77)]. Age of onset [hazard
      ratio (HR) 1.10 (95% CI 1.07, 1.13)], erosive disease [HR 2.03 (95% CI 1.22,
      3.37)], high CRP level [HR 1.09 (95% CI 1.01, 1.18)], smoking [HR 2.39 (95% CI
      1.31, 4.38)] and higher baseline HAQ score [HR 1.53 (95% CI 1.06, 2.20)]
      associated with mortality. CONCLUSION: Current treatment strategies for early RA,
      such as that given in inclusion Period 3, might contribute to the reversal of
      excess mortality in RA.

PMID- 20696680
TI  - Impact of C-reactive protein on absolute reticulocyte count in haemodialysis
      patients: the role of iron status.
AB  - BACKGROUND: The exact mechanisms by which the effects of inflammation on
      erythropoiesis occur are still to be determined. We aimed to examine the relation
      between C-reactive protein (CRP) and erythropoiesis as quantified by the absolute
      reticulocyte count (RTC) and the possible effect of iron status on this
      relationship. METHODS: As part of a study that follows the changes of
      haematologic parameters after the intravenous (IV) administration of iron in 93
      stable haemodialysis (HD) patients, we made a cross-sectional analysis of
      baseline measurements and an analysis of changes in RTC 1 week after baseline
      measurements and iron administration. RESULTS: Multiple linear regression
      analysis revealed that RTC had a positive correlation with CRP; RTC had a
      negative correlation with reticulocyte haemoglobin content (CHr). An interaction
      was also found between CRP and CHr in that CRP had a significant relation to RTC
      only in those patients whose CHr was more than 31.2 pg. At lower values of CHr,
      the correlation between CRP and RTC was not significant. Five days after the IV
      administration of 200 mg iron sucrose, a significant increase of RTC was
      observed, only in those patients with elevated baseline CRP levels who also
      showed an increase in CHr levels from <= 31.2 pg at baseline to >= 31.2 pg post
      administration, supporting the presence of an independent positive correlation
      between CRP and RTC when iron is adequate. CONCLUSIONS: It is indicated that, in
      HD patients, elevated CRP values are associated with increased erythroid
      production only when CHr is quite satisfactory.

PMID- 20696681
TI  - The quantitative evaluation of online haemodiafiltration effect on skin
      hyperpigmentation.
AB  - BACKGROUND: Skin pigmentation is a common problem for dialysis patients, but
      little is known about the factor responsible for the colour intensity. Middle
      molecular-weight (MMW) substances have been suggested to be responsible for the
      skin colour. Several papers have reported that beta(2)-microglobulin (beta(2)-MG)
      correlates with the skin colour, and haemodiafiltration (HDF) is effective to
      reduce the skin hyperpigmentation. However, a quantitative skin colour follow-up
      on patients treated with online haemodiafiltration (online HDF) has not been
      performed. METHODS: Sixty-one patients were enrolled in this study.
      Quantification of skin colour was done using a reflected light colorimeter. Among
      them, 51 patients were under haemodialysis (HD), and the other 10 patients were
      under online HDF. Follow-ups to estimate the skin colour change were performed
      for 6 months. Among 10 patients under online HDF, four patients were also
      investigated by crossover way between HD and online HDF. RESULTS: Compared with
      controls, patients treated with HD had darker skin. The colour value was well
      correlated with age, haematocrit, sex, diabetes and beta(2)-MG but not with Kt/V.
      The skin colour got worse under HD treatment as well as the values of beta(2)-MG,
      but online HDF improved the hyperpigmentation and the beta(2)-MG values.
      CONCLUSIONS: Our data show the effectiveness of online HDF on skin colour and
      suggest that HD patients' skin colour can be improved by modality change.

PMID- 20696682
TI  - Evaluation of left ventricular hypertrophy in patients requiring permanent
      pacing.
AB  - OBJECTIVE: Hypertension may lead to left ventricular hypertrophy, fibrosis and
      degeneration of the conduction system. Our aim was to study the association of
      hypertrophy with certain arrhythmias such as complete atrioventricular block
      (AVB) and symptomatic sick sinus syndrome (SSS) that require implantation of
      permanent pacemaker. METHODS: We studied 130 patients that had been given a
      pacemaker because of complete AVB, 130 patients that had been given a pacemaker
      because of symptomatic SSS and 45 patients without cardiac conduction
      disturbances. In order to estimate left ventricular hypertrophy, indexes of
      relative wall thickness (RWT) and left ventricular mass (LVM) were evaluated by
      echocardiography. RESULTS: We observed significant association between complete
      AVB and abnormal values of echocardiographic indexes. CONCLUSIONS: Our results
      lend further support to the hypothesis that complete AVB is associated with left
      ventricular hypertrophy. This hypothesis is enhanced by the observation that the
      majority of patients with complete AVB were hypertensive.

PMID- 20696683
TI  - Tissue microarray construction from gross specimens: development of a novel
      simple technique.
AB  - BACKGROUND: The tissue microarray (TMA) technique is becoming a useful tool for
      research and quality control methods in surgical pathology. However, the
      widespread use of this technique in routine surgical pathology practice,
      especially in developing nations, is hampered by the high cost of commercially
      available instruments. The authors describe a novel, inexpensive technique of
      construction of TMA from gross specimen. METHODS: The authors used a 16-gauge
      bone marrow trephine biopsy needle to obtain cores from 150 specimens of breast
      carcinoma. These cores were processed in the tissue processor as per the routine
      processing techniques of the department. A recipient block was prepared, followed
      by drilling of a suitable number of holes. The processed tissue cores were
      arrayed into the recipient block. These blocks were used for immunohistochemistry
      and compared with conventional whole tissue sections. RESULTS: Of the 150 cases,
      only two showed suboptimal preservation in the TMA block, and this was also
      reflected in the conventional tissue sections. Immunohistochemical staining for
      oestrogen receptor, progesterone receptor, Her2.neu and Ki-67 was found to be
      satisfactory in 148 cases with the staining intensity comparable with that
      performed on the conventional sections. CONCLUSION: This study describes a
      satisfactory technique for construction of TMA from a gross tumour specimen. Such
      a technique is well suited to centres which handle a high number of cases of a
      particular type, such as breast carcinoma. Further studies on other tumour types
      would help in validating these results.

PMID- 20696684
TI  - Wheat dependent exercise induced anaphylaxis: is this an appropriate terminology?
AB  - BACKGROUND: The presentation of wheat dependent exercise induced anaphylaxis
      (WDEIA) can be variable. A high index of clinical suspicion is required to
      initiate the investigation pathway. Double blind placebo controlled food-exercise
      challenge is the gold standard investigation but the practicality of this test
      limits its application. AIM: To critically analyse the symptoms of WDEIA and
      their correlation with serum specific IgE (sIgE) to romega-5-gliadin. METHODS: 17
      patients were tested for serum sIgE to romega-5-gliadin. The clinical response to
      a diet/exercise intervention protocol was used to assess specificity of a
      positive sIgE to romega-5-gliadin. Length of time to diagnosis, clinical
      likelihood scores, exercise intensity involved and the severity of allergic
      reactions were examined retrospectively. RESULT: 8/10 patients with positive sIgE
      to romega-5-gliadin had a confirmed diagnosis of WDEIA. Half of the WDEIA
      patients had a prolonged time lag to diagnosis (32-62 months) and were initially
      diagnosed with idiopathic anaphylaxis or chronic idiopathic urticaria and
      angioedema. Only three patients had experienced life threatening symptoms
      (Mueller grading 4). A close association was observed between requirements of
      lower exercise intensity to provoke a reaction and diagnostic delay. CONCLUSION:
      Specific IgE to romega-5-gliadin can provide supportive evidence for WDEIA
      without the need of a food-exercise challenge. The wheat-exercise association is
      not obvious in many patients, highlighting the need to consider WDEIA in the
      differential diagnosis of all patients presenting with idiopathic systemic
      reactions. The term anaphylaxis may be inappropriate and it is therefore worth
      considering an alternative terminology such as 'activity dependent wheat allergy'
      to describe this condition.

PMID- 20696685
TI  - Which staging system to use for gynaecological cancers: a survey with
      recommendations for practice in the UK.
AB  - AIMS: There are two commonly used staging systems for gynaecological cancers,
      namely Federation Internationale de Gynecologie et d'Obstetrique (FIGO) and TNM.
      The authors wished to ascertain which staging system is most commonly used in
      dealing with gynaecological cancers in the UK. METHODS: The authors undertook a
      survey among participants in the National Gynaecological Pathology EQA scheme to
      investigate whether gynaecological pathologists in the UK use FIGO or TNM staging
      in their routine reporting of gynaecological cancers. RESULTS: There were 105
      respondents out of 278 participants (38%). Of the analysed results, a majority of
      respondents (64%) use FIGO staging, while 32% use both FIGO and TNM. 80% of
      respondents stated that their multidisciplinary team meeting uses FIGO staging,
      while 18% use both FIGO and TNM. Only an extremely small minority of pathologists
      and multidisciplinary team meetings use TNM alone. A survey of members of the
      British Gynaecological Cancer Society revealed similar findings. CONCLUSIONS:
      Since FIGO and TNM are not always equivalent, and there may be confusion when
      more than one staging system is used, it is recommended that FIGO staging be used
      for gynaecological cancers. The survey revealed support for the use of TNM, as
      well as FIGO, only for cervical cancer, since FIGO does not take the lymph node
      status into account. Given the prevalent practice in the UK, the British
      Association of Gynaecological Pathologists, British Gynaecological Cancer Society
      and gynaecological clinical reference group of the National Cancer Intelligence
      Network recommend that FIGO staging be used for gynaecological cancers with
      recording of the lymph node status for cervical cancer. This may be done by
      providing a TNM stage for this cancer type only or by recording the lymph-node
      status at the multidisciplinary team meeting.

PMID- 20696686
TI  - Primitive mesodermal cells with a neural crest stem cell phenotype predominate
      proliferating infantile haemangioma.
AB  - AIMS: Infantile haemangioma is a tumour of the microvasculature characterised by
      aggressive angiogenesis during infancy and spontaneously gradual involution,
      often leaving a fibro-fatty residuum. The segmental distribution of a subgroup of
      infantile haemangioma, especially those associated with midline structural
      anomalies that constitute posterior fossa malformations-hemangiomas-arterial
      anomalies-cardiac defects-eye abnormalities-sternal cleft and supraumbilical
      raphe syndrome (PHACES), led us to investigate whether neural crest cells might
      be involved in the aetiology of this tumour. METHODS: Immunohistochemical
      staining on paraffin embedded infantile haemangioma sections and
      immunocytochemical staining on cells derived from proliferating haemangioma
      cultures were performed. RESULTS: The endothelium of proliferating infantile
      haemangioma contains abundant cells that express the neurotrophin receptor (p75),
      a cell surface marker that identifies neural crest cells, and also for brachyury,
      a transcription factor expressed in cells of the primitive mesoderm. The
      endothelium is also immunoreactive for the haematopoietic stem cell marker,
      CD133; the endothelial-haematopoietic stem/progenitor marker, CD34; the
      endothelial cell markers, CD31 and VEGFR-2; and the mesenchymal stem cell
      markers, CD29 and vimentin. Additionally, immunoreactivity for the transcription
      factors, Sox 9 and Sox 10, that are expressed by prospective neural crest cells
      was also observed. Cells from microvessel-like structures were isolated from in
      vitro cultured haemangioma tissue explants embedded in a fibrin matrix.
      Immunostaining of these cells showed that they retained expression of the same
      lineage-specific markers that are detected on the paraffin embedded tissue
      sections. CONCLUSIONS: These data infer that infantile haemangioma is derived
      from primitive mesoderm and that the cells within the lesion have a neural crest
      stem cell phenotype, and they express proteins associated with haematopoietic,
      endothelial, neural crest and mesenchymal lineages. The authors propose a model
      to account for the natural progression of infantile haemangioma based upon the
      multipotent expression profile of the primitive mesoderm and their neural crest
      stem cell phenotype to form all the cell lineages detected during infantile
      haemangioma proliferation and involution.

PMID- 20696687
TI  - A study of HER2 gene amplification and protein expression in gastric cancer.
AB  - BACKGROUND: Gastric cancer is a leading cause of cancer-related mortality, and
      current treatment outcomes for advanced disease remain poor. HER2 has been
      identified as a potential candidate for targeted therapy in gastric cancers
      displaying HER2 gene amplification and protein overexpression. AIMS: To study the
      prevalence rate of HER2 gene amplification/overexpression in a local population,
      and determine the concordance rate between the various modalities. METHODS: 128
      gastric cancer samples were analysed by fluorescence (FISH) and chromogenic
      (CISH) in situ hybridisation and immunohistochemistry (IHC). The relation between
      HER2 status and various clinicopathological parameters was also analysed.
      RESULTS: 11.7% (15/128) and 9.4% (12/128) of gastric cancers displayed HER2 gene
      amplification and protein overexpression (score 3+), respectively, with a perfect
      correlation between the FISH and CISH analyses. There was also a significant
      inverse correlation between overall survival and HER2 protein overexpression in
      intestinal-type gastric carcinomas (p<0.05). CONCLUSION: Results, besides
      corroborating existing reports that discrepancies exist between HER2 ISH and IHC
      assays, also suggest the need to rigorously evaluate CISH as an independent
      reference standard for assessment of HER2 amplification in gastric cancers.

PMID- 20696688
TI  - Pleural procedures and thoracic ultrasound: British Thoracic Society Pleural
      Disease Guideline 2010.

PMID- 20696689
TI  - Introduction and methods: British Thoracic Society Pleural Disease Guideline
      2010.

PMID- 20696690
TI  - Management of spontaneous pneumothorax: British Thoracic Society Pleural Disease
      Guideline 2010.

PMID- 20696691
TI  - Management of a malignant pleural effusion: British Thoracic Society Pleural
      Disease Guideline 2010.

PMID- 20696692
TI  - Investigation of a unilateral pleural effusion in adults: British Thoracic
      Society Pleural Disease Guideline 2010.

PMID- 20696693
TI  - Management of pleural infection in adults: British Thoracic Society Pleural
      Disease Guideline 2010.

PMID- 20696694
TI  - Local anaesthetic thoracoscopy: British Thoracic Society Pleural Disease
      Guideline 2010.

PMID- 20696695
TI  - Increasing physical activity in patients with arthritis: a tailored health
      promotion program.
AB  - OBJECTIVE: Despite recent studies showing the benefit of physical activity for
      people with arthritis, the vast majority of persons with arthritis are not
      sufficiently physically active. The purpose of this report is to describe a
      tailored health promotion intervention aimed at increasing physical activity
      among persons with arthritis. The intervention is designed to be useful for
      health systems and insurers interested in a chronic disease management program
      that could be disseminated to large populations of arthritis patients. METHODS:
      The intervention is carried out by a clinician who is designated as the client's
      physical activity advocate. The approach emphasizes motivational interviewing,
      individualized goal setting, tailored strategies for increasing physical activity
      and for monitoring progress, and a plan of 2 years of follow-up. The intervention
      includes a standardized assessment of barriers to and strengths supporting
      increased lifestyle physical activity. A randomized, controlled trial is underway
      to evaluate the efficacy and cost-effectiveness of this intervention. CONCLUSION:
      This intervention is unique in that it implements a program tailored to the
      individual that focuses on lifestyle physical activity and long-term monitoring.
      The approach recognizes that persons with arthritis present with varying levels
      of motivation for change in physical activity and that behavior change can take a
      long time to become habitual.

PMID- 20696696
TI  - Growth hormone and memory.
AB  - Growth hormone (GH) replacement unequivocally benefits growth, body composition,
      cardiovascular risk factors and quality of life. Less is known about the effects
      of GH on learning and memory. The recent paper on 'early onset - GH deficiency
      (GHD) results in spatial memory impairment in mid life - and is prevented by GH
      supplementation' by Nieves-Martinez importantly adds to this literature. Other
      data suggest that GH beneficially affects cognitive function in rats. In man,
      treatment of GHD has been associated with improvements in measures of memory and
      attention. There are also differences in verbal memory of patients with childhood
      onset GHD. Further questions remain, and the beneficial effects or otherwise of
      treating GHD in different age groups remain to be better defined. Certainly for
      reasons of maturation of neural connections and their development to young
      adulthood contemporaneous with rises in GH and IGF1 make these important areas
      for further study in man. Lastly because of what we already know in terms of
      cognitive effects of GHD, it is important to replace GH when studying other
      potential causes of adverse effects on cognition, for example, with radiotherapy.

PMID- 20696697
TI  - Novel pharmacological MC4R agonists can efficiently activate mutated MC4R from
      obese patient with impaired endogenous agonist response.
AB  - Human melanocortin 4 receptor (hMC4R) mutations with in vitro functional effects
      are responsible for 0.5-2.5% of severe obesity. Designing ligands that are able
      to counteract this in vitro-associated molecular defect is crucial to develop
      specific anti-obesity drugs in these genetically associated cases. We analyzed
      the in vitro effect of two novel melanocortin agonists, IRC-022493 and IRC
      022511, on typical hMC4R mutations chosen based on the nature of their functional
      alterations, i.e. intracytoplasmic retention and/or reduced basal activity and/or
      reduced alpha-MSH potency. We assessed the in vitro ability of IRC-022493 and IRC
      022511 to bind and activate hMC4R mutants. These mutations were found earlier in
      11 obese French patients (median age (range) was 17.6 years (5.7-48.0) and body
      mass index (BMI)-Z-score 4.2 s.d. (1.5-5.5). The MC4R agonists were responsible
      for a significant activation of mutated hMC4R depending on the functional
      characteristics of the mutations. Both agonists were able to activate mutated
      hMC4R with decreased alpha-MSH potency, associated with or without decreased
      basal activity, to the same extent than alpha-MSH in wild-type MC4R. This result
      suggests that those mutations would be the best targets for the MC4R agonists
      among MC4R mutation-bearing obese patients. No specific clinical phenotype was
      associated with the differential response to pharmacological agonists. We
      identified two novel melanocortin agonists that were able in vitro to efficiently
      activate mutated hMC4R with impaired endogenous agonist functional response.
      These results stimulate interest in the development of these drugs for hMC4R
      mutations-associated obesity.

PMID- 20696698
TI  - MHC class II-restricted antigen presentation by plasmacytoid dendritic cells
      inhibits T cell-mediated autoimmunity.
AB  - Although plasmacytoid dendritic cells (pDCs) express major histocompatibility
      complex class II (MHCII) molecules, and can capture, process, and present
      antigens (Ags), direct demonstrations that they function as professional Ag
      presenting cells (APCs) in vivo during ongoing immune responses remain lacking.
      We demonstrate that mice exhibiting a selective abrogation of MHCII expression by
      pDCs develop exacerbated experimental autoimmune encephalomyelitis (EAE) as a
      consequence of enhanced priming of encephalitogenic CD4(+) T cell responses in
      secondary lymphoid tissues. After EAE induction, pDCs are recruited to lymph
      nodes and establish MHCII-dependent myelin-Ag-specific contacts with CD4(+) T
      cells. These interactions promote the selective expansion of myelin-Ag-specific
      natural regulatory T cells that dampen the autoimmune T cell response. pDCs thus
      function as APCs during the course of EAE and confer a natural protection against
      autoimmune disease development that is mediated directly by their ability to
      present of Ags to CD4(+) T cells in vivo.

PMID- 20696699
TI  - Central nervous system (CNS)-resident natural killer cells suppress Th17
      responses and CNS autoimmune pathology.
AB  - Natural killer (NK) cells of the innate immune system can profoundly impact the
      development of adaptive immune responses. Inflammatory and autoimmune responses
      in anatomical locations such as the central nervous system (CNS) differ
      substantially from those found in peripheral organs. We show in a mouse model of
      multiple sclerosis that NK cell enrichment results in disease amelioration,
      whereas selective blockade of NK cell homing to the CNS results in disease
      exacerbation. Importantly, the effects of NK cells on CNS pathology were
      dependent on the activity of CNS-resident, but not peripheral, NK cells. This
      activity of CNS-resident NK cells involved interactions with microglia and
      suppression of myelin-reactive Th17 cells. Our studies suggest an organ-specific
      activity of NK cells on the magnitude of CNS inflammation, providing potential
      new targets for therapeutic intervention.

PMID- 20696700
TI  - Mutant p53 facilitates somatic cell reprogramming and augments the malignant
      potential of reprogrammed cells.
AB  - p53 deficiency enhances the efficiency of somatic cell reprogramming to a
      pluripotent state. As p53 is usually mutated in human tumors and many mutated
      forms of p53 gain novel activities, we studied the influence of mutant p53 (mut
      p53) on somatic cell reprogramming. Our data indicate a novel gain of function
      (GOF) property for mut-p53, which markedly enhanced the efficiency of the
      reprogramming process compared with p53 deficiency. Importantly, this novel
      activity of mut-p53 induced alterations in the characteristics of the
      reprogrammed cells. Although p53 knockout (KO) cells reprogrammed with only Oct4
      and Sox2 maintained their pluripotent capacity in vivo, reprogrammed cells
      expressing mutant p53 lost this capability and gave rise to malignant tumors.
      This novel GOF of mut-p53 is not attributed to its effect on proliferation, as
      both p53 KO and mut-p53 cells displayed similar proliferation rates. In addition,
      we demonstrate an oncogenic activity of Klf4, as its overexpression in either p53
      KO or mut-p53 cells induced aggressive tumors. Overall, our data show that
      reprogrammed cells with the capacity to differentiate into the three germ layers
      in vitro can form malignant tumors, suggesting that in genetically unstable
      cells, such as those in which p53 is mutated, reprogramming may result in the
      generation of cells with malignant tumor-forming potential.

PMID- 20696701
TI  - Distinct contracted conformations of the Tcra/Tcrd locus during Tcra and Tcrd
      recombination.
AB  - Studies have suggested that antigen receptor loci adopt contracted conformations
      to promote long-distance interactions between gene segments during V(D)J
      recombination. The Tcra/Tcrd locus is unique because it undergoes highly
      divergent Tcrd and Tcra recombination programs in CD4(-)CD8(-) double negative
      (DN) and CD4(+)CD8(+) double positive (DP) thymocytes, respectively. Using three
      dimensional fluorescence in situ hybridization, we asked whether these divergent
      recombination programs are supported by distinct conformational states of the
      Tcra/Tcrd locus. We found that the 3' portion of the locus is contracted in DN
      and DP thymocytes but not in B cells. Remarkably, the 5' portion of the locus is
      contracted in DN thymocytes but is decontracted in DP thymocytes. We propose that
      the fully contracted conformation in DN thymocytes allows Tcrd rearrangements
      involving V(delta) gene segments distributed over 1 Mb, whereas the unique 3'
      contracted, 5'-decontracted conformation in DP thymocytes biases initial Tcra
      rearrangements to the most 3' of the available V(alpha) gene segments. This would
      maintain a large pool of distal 5' V(alpha) gene segments for subsequent rounds
      of recombination. Thus, distinct contracted conformations of the Tcra/Tcrd locus
      may facilitate a transition from a Tcrd to a Tcra mode of recombination during
      thymocyte development.

PMID- 20696703
TI  - Yukiko Goda: memories are made of this.

PMID- 20696704
TI  - The cell biology of taste.
AB  - Taste buds are aggregates of 50-100 polarized neuroepithelial cells that detect
      nutrients and other compounds. Combined analyses of gene expression and cellular
      function reveal an elegant cellular organization within the taste bud. This
      review discusses the functional classes of taste cells, their cell biology, and
      current thinking on how taste information is transmitted to the brain.

PMID- 20696705
TI  - Structure of the Sec13-Sec16 edge element, a template for assembly of the COPII
      vesicle coat.
AB  - Ancestral coatomer element 1 (ACE1) proteins assemble latticework coats for COPII
      vesicles and the nuclear pore complex. The ACE1 protein Sec31 and Sec13 make a
      2:2 tetramer that forms the edge element of the COPII outer coat. In this study,
      we report that the COPII accessory protein Sec16 also contains an ACE1. The 165
      kD crystal structure of the central domain of Sec16 in complex with Sec13 was
      solved at 2.7-A resolution. Sec16 and Sec13 also make a 2:2 tetramer, another
      edge element for the COPII system. Domain swapping at the ACE1-ACE1 interface is
      observed both in the prior structure of Sec13-Sec31 and in Sec13-Sec16. A Sec31
      mutant in which domain swapping is prevented adopts an unprecedented laminated
      structure, solved at 2.8-A resolution. Our in vivo data suggest that the ACE1
      element of Sec31 can functionally replace the ACE1 element of Sec16. Our data
      support Sec16 as a scaffold for the COPII system and a template for the Sec13
      Sec31 coat.

PMID- 20696706
TI  - ER sliding dynamics and ER-mitochondrial contacts occur on acetylated
      microtubules.
AB  - The endoplasmic reticulum (ER) network is extremely dynamic in animal cells, yet
      little is known about the mechanism and function of its movements. The most
      common ER dynamic, termed ER sliding, involves ER tubule extension along stable
      microtubules (MTs). In this study, we show that ER sliding occurs on nocodazole
      resistant MTs that are posttranslationally modified by acetylation. We
      demonstrate that high MT curvature is a good indicator of MT acetylation and show
      in live cells that ER sliding occurs predominantly on these curved, acetylated
      MTs. Furthermore, increasing MT acetylation by drug treatment increases the
      frequency of ER sliding. One purpose of the ER sliding on modified MT tracts
      could be to regulate its interorganelle contacts. We find that all mitochondria
      and many endosomes maintain contact with the ER despite the movements of each.
      However, mitochondria, but not endosomes, preferentially localize to acetylated
      MTs. Thus, different ER dynamics may occur on distinct MT populations to
      establish or maintain contacts with different organelles.

PMID- 20696707
TI  - Model-based dissection of CD95 signaling dynamics reveals both a pro- and
      antiapoptotic role of c-FLIPL.
AB  - Cellular FADD-like interleukin-1beta-converting enzyme inhibitory proteins (c
      FLIPs; isoforms c-FLIP long [c-FLIP(L)], c-FLIP short [c-FLIP(S)], and c-FLIP
      Raji [c-FLIP(R)]) regulate caspase-8 activation and death receptor (DR)-induced
      apoptosis. In this study, using a combination of mathematical modeling, imaging,
      and quantitative Western blots, we present a new mathematical model describing
      caspase-8 activation in quantitative terms, which highlights the influence of c
      FLIP proteins on this process directly at the CD95 death-inducing signaling
      complex. We quantitatively define how the stoichiometry of c-FLIP proteins
      determines sensitivity toward CD95-induced apoptosis. We show that c-FLIP(L) has
      a proapoptotic role only upon moderate expression in combination with strong
      receptor stimulation or in the presence of high amounts of one of the short c
      FLIP isoforms, c-FLIP(S) or c-FLIP(R). Our findings resolve the present
      controversial discussion on the function of c-FLIP(L) as a pro- or antiapoptotic
      protein in DR-mediated apoptosis and are important for understanding the
      regulation of CD95-induced apoptosis, where subtle differences in c-FLIP
      concentrations determine life or death of the cells.

PMID- 20696708
TI  - Drosophila Mtm and class II PI3K coregulate a PI(3)P pool with cortical and
      endolysosomal functions.
AB  - Reversible phosphoinositide phosphorylation provides a dynamic membrane code that
      balances opposing cell functions. However, in vivo regulatory relationships
      between specific kinases, phosphatases, and phosphoinositide subpools are not
      clear. We identified myotubularin (mtm), a Drosophila melanogaster MTM1/MTMR2
      phosphoinositide phosphatase, as necessary and sufficient for immune cell
      protrusion formation and recruitment to wounds. Mtm-mediated turnover of
      endosomal phosphatidylinositol 3-phosphate (PI(3)P) pools generated by both class
      II and III phosphatidylinositol 3-kinases (Pi3K68D and Vps34, respectively) is
      needed to down-regulate membrane influx, promote efflux, and maintain
      endolysosomal homeostasis. Endocytosis, but not endolysosomal size, contributes
      to cortical remodeling by mtm function. We propose that Mtm-dependent regulation
      of an endosomal PI(3)P pool has separable consequences for endolysosomal
      homeostasis and cortical remodeling. Pi3K68D depletion (but not Vps34) rescues
      protrusion and distribution defects in mtm-deficient immune cells and restores
      functions in other tissues essential for viability. The broad interactions
      between mtm and class II Pi3K68D suggest a novel strategy for rebalancing PI(3)P
      mediated cell functions in MTM-related human disease.

PMID- 20696709
TI  - Syndecan-3 and Notch cooperate in regulating adult myogenesis.
AB  - Skeletal muscle postnatal growth and repair depend on satellite cells and are
      regulated by molecular signals within the satellite cell niche. We investigated
      the molecular and cellular events that lead to altered myogenesis upon genetic
      ablation of Syndecan-3, a component of the satellite cell niche. In the absence
      of Syndecan-3, satellite cells stall in S phase, leading to reduced
      proliferation, increased cell death, delayed onset of differentiation, and
      markedly reduced numbers of Pax7(+) satellite cells accompanied by myofiber
      hypertrophy and an increased number of centrally nucleated myofibers. We show
      that the aberrant cell cycle and impaired self-renewal of explanted Syndecan-3
      null satellite cells are rescued by ectopic expression of the constitutively
      active Notch intracellular domain. Furthermore, we show that Syndecan-3 interacts
      with Notch and is required for Notch processing by ADAM17/tumor necrosis factor
      alpha-converting enzyme (TACE) and signal transduction. Together, our data
      support the conclusion that Syndecan-3 and Notch cooperate in regulating
      homeostasis of the satellite cell population and myofiber size.

PMID- 20696710
TI  - KIF17 stabilizes microtubules and contributes to epithelial morphogenesis by
      acting at MT plus ends with EB1 and APC.
AB  - Epithelial polarization is associated with selective stabilization and
      reorganization of microtubule (MT) arrays. However, upstream events and
      downstream consequences of MT stabilization during epithelial morphogenesis are
      still unclear. We show that the anterograde kinesin KIF17 localizes to MT plus
      ends, stabilizes MTs, and affects epithelial architecture. Targeting of KIF17 to
      plus ends of growing MTs requires kinesin motor activity and interaction with
      EB1. In turn, KIF17 participates in localizing adenomatous polyposis coli (APC)
      to the plus ends of a subset of MTs. We found that KIF17 affects MT dynamics,
      polymerization rates, and MT plus end stabilization to generate
      posttranslationally acetylated MTs. Depletion of KIF17 from cells growing in
      three-dimensional matrices results in aberrant epithelial cysts that fail to
      generate a single central lumen and to polarize apical markers. These findings
      implicate KIF17 in MT stabilization events that contribute to epithelial
      polarization and morphogenesis.

PMID- 20696711
TI  - CAZymes Analysis Toolkit (CAT): web service for searching and analyzing
      carbohydrate-active enzymes in a newly sequenced organism using CAZy database.
AB  - The Carbohydrate-Active Enzyme (CAZy) database provides a rich set of manually
      annotated enzymes that degrade, modify, or create glycosidic bonds. Despite rich
      and invaluable information stored in the database, software tools utilizing this
      information for annotation of newly sequenced genomes by CAZy families are
      limited. We have employed two annotation approaches to fill the gap between
      manually curated high-quality protein sequences collected in the CAZy database
      and the growing number of other protein sequences produced by genome or
      metagenome sequencing projects. The first approach is based on a similarity
      search against the entire nonredundant sequences of the CAZy database. The second
      approach performs annotation using links or correspondences between the CAZy
      families and protein family domains. The links were discovered using the
      association rule learning algorithm applied to sequences from the CAZy database.
      The approaches complement each other and in combination achieved high specificity
      and sensitivity when cross-evaluated with the manually curated genomes of
      Clostridium thermocellum ATCC 27405 and Saccharophagus degradans 2-40. The
      capability of the proposed framework to predict the function of unknown protein
      domains and of hypothetical proteins in the genome of Neurospora crassa is
      demonstrated. The framework is implemented as a Web service, the CAZymes Analysis
      Toolkit, and is available at http://cricket.ornl.gov/cgi-bin/cat.cgi.

PMID- 20696713
TI  - Harm reduction for unintentional poisoning.

PMID- 20696712
TI  - Identification and functional characterization of the HpALG11 and the HpRFT1
      genes involved in N-linked glycosylation in the methylotrophic yeast Hansenula
      polymorpha.
AB  - The initial steps in N-linked glycosylation involve the synthesis of a lipid
      linked core oligosaccharide followed by the transfer of the core glycan to
      nascent polypeptides in the endoplasmic reticulum (ER). In this study, we have
      identified two genes, HpALG11and HpRFT1, in the metylotrophic yeast Hansenula
      polymorpha. Detailed analysis of the glycan structures of the N-linked glycans of
      secreted recombinant glucose oxidase in mutant strains Hpalg3Delta, Hpalg11Delta,
      and Hpalg3Deltaalg11Delta with the assistance of over-expression of RFT1 was
      performed by linkage-specific mannosidase digestion. The results suggest that
      HpALG11 and HpRFT1 were responsible for catalyzing the sequential transfer of
      terminal alpha-1,2-Man residues to form the Man(5)GlcNAc(2)-PP-Dol intermediate
      at the cytosolic side of the ER before flipping to the luminal side and encoding
      an evolutionarily conserved protein required for the translocation of
      Man(5)GlcNAc(2)-PP-Dol from the cytoplasmic to the lumenal leaflet of the ER
      membrane, respectively. Deletion of the HpALG11 gene leads to poor growth and
      temperature-sensitive lethality, whereas over-expression of HpRft1p can improve
      growth of the Hpalg11Delta and Hpalg3Deltaalg11Delta strains. Furthermore,
      deletion of the HpALG11 gene in the Hpalg3Delta strain resulted in the secretion
      of glycoproteins with a predicted structure mainly containing trimannosyl core N
      linked glycans (Man(3)GlcNAc(2)).

PMID- 20696715
TI  - An investigation into methods to develop indicators to measure injury related
      impairment.
AB  - OBJECTIVE: To investigate whether valid indicators of injury-related impairment
      could be developed based on data from a New Zealand national no-fault accident
      insurance scheme. DESIGN: The feasibility of (1) developing impairment related
      indicators using insurance data directly, and (2) deriving diagnosis specific
      probability of impairment measures based on hospital discharge data were
      investigated. SETTING: The source data were lump sum payment data for permanent
      impairment arising from an injury event between 1 April 2002 and 31 October 2006,
      and hospital discharge data for injury events between 1 April 2002 and 31
      December 2005. MAIN OUTCOME MEASURE: A threat of impairment measure was developed
      that was based on a list of International Classification of Diseases codes
      (version 10) which, if assessed would attract a lump sum payment for permanent
      impairment, and would almost always be expected to be admitted to hospital.
      RESULTS: A group of approximately 80 diagnoses satisfying the above criteria were
      identified. The trend in age standardised injury rates for the threat of
      impairment indicator is consistent with the trend for the New Zealand threat to
      life indicator. CONCLUSIONS: This work has provided a method for the development
      of hospital discharge-based serious threat of impairment injury indicators. This
      is an important first step in developing a comprehensive package of (threat of)
      disability indicators.

PMID- 20696716
TI  - Estimates of drowning morbidity and mortality adjusted for exposure to risk.
AB  - OBJECTIVES: To estimate the rate of unintentional drowning mortality and
      hospitalised morbidity using population-based, population-risk and person-time
      denominator data and to compare the estimates obtained. To then compare exposure
      based rates for drowning with road traffic death rates. METHOD: Retrospective
      analysis of unintentional drowning mortality and hospitalised morbidity of New
      South Wales (NSW, Australia) residents 16+ years of age during 1 January to 31
      December 2005. Information on population-risk and person-time risk was obtained
      from the 2005 NSW Population Health Survey. Analysis of road traffic death data
      from NSW and population and person-time risk estimates from the Survey of Vehicle
      Use, Household Travel Surveys and Roads and Traffic Authority Speed Surveys in
      2005. RESULTS: Estimated drowning mortality and hospitalised morbidity rates for
      adults were higher using population-risk and person-time risk exposures compared
      to a population-based exposure. Population-based estimates of road traffic
      mortality were four times higher than drowning mortality rates. In contrast,
      exposure adjusted person-time estimates for drowning were 200 times higher than
      road traffic fatalities. CONCLUSIONS: Many injury risks are underestimated when
      the total age-specific population is used to calculate an injury rate instead of
      actual population-risk or person-time exposure. This can result in the
      identification of misleading priorities for injury prevention. Drowning risk is
      strikingly higher than previously thought based on population-based estimates.
      This information is important for decision-making and policy development as it
      provides a basis for comparing the inherent risk in exposure to hazards with
      potential to cause injury.

PMID- 20696717
TI  - Field triage: optimising injury outcomes through use of a revised on-scene
      decision-making protocol.

PMID- 20696719
TI  - Five Ws on falls in disability patients.

PMID- 20696720
TI  - Abusive head trauma: judicial admissions highlight violent and repetitive
      shaking.
AB  - OBJECTIVE: Confessions are uncommon in abusive head trauma (AHT) cases, and there
      is debate over whether shaking alone can cause the injuries characteristic of
      AHT. The objective of this article is to correlate legal statements by
      perpetrators with medical documentation to offer insights into the mechanism of
      injury. METHODS: In this retrospective observational study we examined forensic
      evidence from 112 cases referred for AHT over a 7-year period. We compared 29
      cases in which a perpetrator confessed to violence toward the child with 83 cases
      in which there was no confession. Inclusion criteria were subdural hematoma (SDH)
      on computed tomography and perpetrator admission of a causal relationship between
      the violence inflicted and the child's symptoms. Groups were compared by using
      Student's t test for age and Fisher's exact test for gender, death, fractures,
      retinal hemorrhages, ecchymoses, symptoms, and SDH patterns. All medical records
      from birth to diagnosis, imaging studies, and written investigation reports were
      reviewed. RESULTS: All confessions came from forensic investigations. There was
      no statistically significant difference between the 2 groups for any of the
      variables studied. Shaking was described as extremely violent (100%) and was
      repeated (55%) from 2 to 30 times (mean: 10) because it stopped the infant's
      crying (62.5%). Impact was uncommon (24%). No correlation was found between
      repeated shaking and SDH densities. CONCLUSIONS: This unique forensic case series
      confirms the violence of shaking. The high frequency of habitual AHT is a strong
      argument for reporting suspected cases to judicial authorities and helps to
      explain the difficulty in dating the injuries.

PMID- 20696721
TI  - Pediatric HIV costs across three treatment eras from 1986 to 2007.
AB  - OBJECTIVE: Life has changed dramatically for infants exposed perinatally to HIV
      to HIV primarily because of a successful translational research program that has
      also affected treatment costs. We compared treatment costs among HIV+ patients in
      an HIV/AIDS specialty clinic across 3 treatment eras: monotherapy (pre-1990),
      combination therapy (1990-1996), and highly active antiretroviral therapy (HAART)
      (1997-2007). We also estimated cumulative health care costs among pediatric
      HIV/AIDS patients born in each era. PATIENTS AND METHODS: Data on health care use
      were collected from medical records of 126 infants born to HIV+ mothers during a
      21-year period (1986-2007) (728 person-years). The Drug Topics Red Book 1999 was
      used for drug costs, the Current Procedural Terminology Medicare Fee Schedule
      codes for outpatient costs, and the Healthcare Cost and Utilization Project Kids'
      Inpatient Database for inpatient costs. Generalized estimating equations and
      bootstrapped ordinary least-squares models were used to determine 2007 costs,
      cumulative costs, and cost savings. RESULTS: Lifetime cost savings with HAART
      were $6.7 to $23.3 million, depending on incidence. Average total costs per HIV+
      person per month were $1306 ($318 for drugs, $896 for total medical) in the
      monotherapy era, $2289 ($891 for drugs, $1180 for total medical) in the
      combination-therapy era, and $1814 ($1241 for drugs, $320 for total medical) in
      the HAART era. Total costs during the HAART era were 25.2% lower than costs
      during the combination-therapy era, because the 34% higher HAART drug costs were
      compensated for by total medical costs (inpatient+outpatient) that were 57%
      lower, which was a significant change (P<.001). The cumulative costs for
      treatment of an HIV+ patient were highest during the monotherapy era ($196,860)
      and lowest during the HAART era ($181,436). CONCLUSIONS: Our results show that
      the cost burden for the treatment of HIV+ pediatric patients has decreased over
      time. This historical examination of treatment-era costs demonstrates the value
      of technologic advances in treatment.

PMID- 20696722
TI  - Role of prenatal characteristics and early growth on pubertal attainment of
      British girls.
AB  - OBJECTIVES: The objective of this study was to explore the influence of maternal
      prenatal characteristics and behaviors and of weight and BMI gain during early
      childhood on the timing of various puberty outcomes in girls who were enrolled in
      the Avon Longitudinal Study of Parents and Children. METHODS: Repeated self
      assessments of pubertal development were obtained from approximately 4000 girls
      between the ages of 8 and 14. Data on prenatal characteristics and weight at
      birth and 2, 9, and 20 months of age were obtained from questionnaires, birth
      records, and clinic visits. Infants' weights were converted to weight-for-age and
      BMI SD scores (SDSs; z scores), and change values were obtained for the 0- to 20
      month and other intervals within that age range. We used parametric survival
      models to estimate associations with age of entry into Tanner stages of breast
      and pubic hair and menarche. RESULTS: Maternal initiation of menarche at age<12,
      smoking during pregnancy, and primiparity were associated with earlier puberty. A
      1-unit increase in the weight SDS change values for the 0- to 20-month age
      interval was associated with earlier ages of entry into pubertal outcomes (0.19
      0.31 years). Increases in the BMI SDS change values were also associated with
      earlier entry into pubertal outcomes (0.07-0.11 years). CONCLUSIONS: Many of the
      maternal prenatal characteristics and weight and BMI gain during infancy seemed
      to have similar influences across different puberty outcomes. Either such early
      factors have comparable influences on each of the hormonal processes involved in
      puberty, or processes are linked and awakening of 1 aspect triggers the others.

PMID- 20696723
TI  - Prevalence of streptococcal pharyngitis and streptococcal carriage in children: a
      meta-analysis.
AB  - OBJECTIVES: Prevalence estimates can help clinicians make informed decisions
      regarding diagnostic testing of children who present with symptoms of
      pharyngitis. We conducted a meta-analysis to determine the (1) prevalence of
      streptococcal infection among children who presented with sore throat and (2)
      prevalence of streptococcal carriage among asymptomatic children. METHODS: We
      searched Medline for articles on pediatric streptococcal pharyngitis. We included
      articles in our review when they contained data on the prevalence of group A
      Streptococcus (GAS) from pharyngeal specimens in children who were younger than
      18 years. Two evaluators independently reviewed, rated, and abstracted data from
      each article. Prevalence estimates were pooled in a meta-analysis and stratified
      according to age group. RESULTS: Of the 266 articles retrieved, 29 met all
      inclusion criteria. Among children of all ages who present with sore throat, the
      pooled prevalence of GAS was 37% (95% confidence interval [CI]: 32%-43%).
      Children who were younger than 5 years had a lower prevalence of GAS (24% [95%
      CI: 21%-26%]). The prevalence of GAS carriage among well children with no signs
      or symptoms of pharyngitis was 12% (95% CI: 9%-14%). CONCLUSIONS: Prevalence
      rates of GAS disease and carriage varied by age; children who were younger than 5
      years had lower rates of throat cultures that were positive for GAS.

PMID- 20696724
TI  - Pragmatic scoring system for pharyngitis in low-resource settings.
AB  - OBJECTIVE: Our objective was to develop an easy, safe, pragmatic, clinical
      scoring system that would allow decreases in unnecessary treatment with
      antimicrobial agents in low-resource settings. METHODS: Children with pharyngitis
      were enrolled prospectively from 2 public hospitals and 1 medical unit in
      Brasilia, Brazil, over 17 months. Attending clinicians completed a questionnaire
      and a previously published scoring system for pharyngitis before performing
      throat swabs and group A streptococcus (GAS) rapid antigen-detection tests. Data
      from this study were added to those collected in 2004, to assess the performance
      of each item of the scoring system. The performance of the new clinical decision
      rule was determined with a receiver operating characteristic curve. The final
      outcome of the model was assessed on the basis of sensitivity, specificity, and
      positive likelihood ratio for non-GAS infections with the clinical approach,
      compared with throat culture or rapid antigen-detection test results. RESULTS: A
      total of 576 children were included, among whom 400 had non-GAS pharyngitis. The
      use of our new clinical decision rule would allow for 35% to 55% antibiotic
      reduction, with 88% specificity. CONCLUSIONS: This clinical decision rule could
      reduce unnecessary antibiotic treatment significantly in low-resource settings.

PMID- 20696725
TI  - Human Salmonella infections linked to contaminated dry dog and cat food, 2006
      2008.
AB  - OBJECTIVE: Human Salmonella infections associated with dry pet food have not been
      previously reported. We investigated such an outbreak of Salmonella
      Schwarzengrund and primarily affecting young children. PATIENTS AND METHODS: Two
      multistate case-control studies were conducted to determine the source and mode
      of infections among case-patients with the outbreak strain. Study 1 evaluated
      household exposures to animals and pet foods, and study 2 examined risk factors
      for transmission among infant case-patients. Environmental investigations were
      conducted. RESULTS: Seventy-nine case-patients in 21 states were identified; 48%
      were children aged 2 years or younger. Case-households were significantly more
      likely than control households to report dog contact (matched odds ratio [mOR]:
      3.6) and to have recently purchased manufacturer X brands of dry pet food (mOR:
      6.9). Illness among infant case-patients was significantly associated with
      feeding pets in the kitchen (OR: 4.4). The outbreak strain was isolated from
      opened bags of dry dog food produced at plant X, fecal specimens from dogs that
      ate manufacturer X dry dog food, and an environmental sample and unopened bags of
      dog and cat foods from plant X. More than 23 000 tons of pet foods were recalled.
      After additional outbreak-linked illnesses were identified during 2008, the
      company recalled 105 brands of dry pet food and permanently closed plant X.
      CONCLUSIONS: Dry dog and cat foods manufactured at plant X were linked to human
      illness for a 3-year period. This outbreak highlights the importance of proper
      handling and storage of pet foods in the home to prevent human illness,
      especially among young children.

PMID- 20696726
TI  - Intranasal medication delivery for children: a brief review and update.
AB  - With the exception of oral medications, most traditional forms of drug delivery
      outside the operating suite require an injection with a needle-a process that is
      painful and anxiety-provoking, risks needle stick injury, and consumes valuable
      staff time. In addition, intravenous access in pediatrics may be difficult for
      inexperienced providers. Intranasal medication delivery offers an alternative
      method of drug delivery that is often as fast in onset as intravenous medication,
      usually painless, inexpensive, easy to deliver, and effective in a variety of
      acute pediatric medical conditions. This article briefly reviews the most common
      uses for intranasal medication delivery in pediatrics: pain control, anxiolysis,
      and seizure control.

PMID- 20696728
TI  - Highlighting violent and repetitive shaking.

PMID- 20696727
TI  - Pubertal assessment method and baseline characteristics in a mixed longitudinal
      study of girls.
AB  - OBJECTIVES: The objective of this study was to describe the assessment methods
      and maturation status for a multisite cohort of girls at baseline recruitment and
      at ages 7 and 8 years. METHODS: The method for pubertal maturation staging was
      developed collaboratively across 3 sites. Girls at ages 6 to 8 years were
      recruited at 3 sites: East Harlem, New York; greater Cincinnati metropolitan
      area; and San Francisco Bay area, California. Baseline characteristics were
      obtained through interviews with caregivers and anthropometric measurements by
      trained examiners; breast stage 2 was defined as onset of pubertal maturation.
      The kappa statistic was used to evaluate agreement between master trainers and
      examiners. Logistic regression models were used to identify factors that are
      associated with pubertal maturation and linear regression models to examine
      factors that are associated with height velocity. RESULTS: The baseline cohort
      included 1239 girls. The proportion of girls who had attained breast stage 2
      varied by age, race/ethnicity, BMI percentile, and site. At 7 years, 10.4% of
      white, 23.4% of black non-Hispanic, and 14.9% of Hispanic girls had attained
      breast stage>or=2; at 8 years, 18.3%, 42.9%, and 30.9%, respectively, had
      attained breast stage>or=2. The prime determinant of height velocity was pubertal
      status. CONCLUSIONS: In this multisite study, there was substantial agreement
      regarding pubertal staging between examiners across sites. The proportion of
      girls who had breast development at ages 7 and 8 years, particularly among white
      girls, is greater than that reported from studies of girls who were born 10 to 30
      years earlier.

PMID- 20696729
TI  - Early weaning from incubator and early discharge of preterm infants: randomized
      clinical trial.
AB  - OBJECTIVE: The goal was to assess the feasibility of earlier weaning from the
      incubator for preterm infants. METHODS: This was a prospective, randomized study
      with preterm infants with birth weights of <1600 g who were admitted to a
      neonatal subintensive ward. Findings for 47 infants who were transferred from an
      incubator to an open crib at >1600 g (early transition group) were compared with
      those for 47 infants who were transferred from an incubator to an open crib at
      >1800 g (standard transition [ST] group). The primary outcome of the study was
      length of stay. Secondary outcomes were the number of infants returned to an
      incubator, the growth velocity in an open crib and during the first week at home,
      the proportions of breastfeeding at discharge and during the first week at home,
      and the hospital readmission rate. RESULTS: The length of stay was significantly
      shorter in the early transition group than in the standard transition group (23.5
      vs 33 days; P=.0002). No infants required transfer back to the incubator. Only 1
      infant in the standard transition group was readmitted to the hospital during the
      first week after discharge. Growth velocities and individual amounts of
      breastfeeding were similar between the 2 groups. CONCLUSION: In this study,
      weaning of moderately preterm infants from incubators to open cribs at 1600 g was
      safe and resulted in earlier discharge.

PMID- 20696730
TI  - Effects of upgraded child restraint law designed to increase booster seat use in
      New York.
AB  - OBJECTIVE: The goal was to examine the association between the New York State
      (NYS) upgraded child restraint law (UCRL) implemented in 2005 and the traffic
      injury rate among 4- to 6-year-old children in New York State. METHODS: A
      before/after comparison study of population-based, traffic injury rates for 4- to
      6-year-old children, using 0- to 3-year-old children as a comparison group, was
      performed. The effects of UCRL on injury rates among 0- to 3-year-old and 4- to 6
      year-old motor vehicle passengers were estimated by using monthly injury count
      data from the NYS Department of Motor Vehicles Accident Information System.
      RESULTS: Children 4 to 6 years of age experienced an 18% reduction in traffic
      injury rate (adjusted rate ratio [aRR]: 0.82 [95% confidence interval [CI]: 0.79
      0.85]) after UCRL implementation, whereas the injury rate for children 0 to 3
      years of age, who were not directly affected by the UCRL, did not change
      appreciably (aRR: 0.95 [95% CI: 0.90-0.99]). In Poisson regression analysis, the
      aRR for injury for 4- to 6-year-old children was 1.06 (95% CI: 0.92-1.22]) with
      adjustment for monthly child restraint use rates, which reveals that the
      significant reduction in the injury rate among 4- to 6-year-old children was
      mainly attributable to the 72% increase in the child restraint use rate after
      UCRL implementation (from 29% before UCRL implementation to 50% after
      implementation). CONCLUSIONS: This is the first study comparing traffic injury
      rates for booster seat-aged children before and after implementation of the
      booster seat law in a single state.

PMID- 20696731
TI  - Receptive language and educational attainment for sexually abused females.
AB  - OBJECTIVES: The objective of this study was to test whether the experience of
      childhood sexual abuse is associated with long-term receptive language
      acquisition and educational attainment deficits for females. METHODS: Females
      with substantiated familial childhood sexual abuse (n=84) and a nonabused
      comparison group (n=102) were followed prospectively for 18 years. Receptive
      language ability was assessed at 6 time points across distinct stages of
      development, including childhood, adolescence, and young adulthood. Rates of high
      school graduation and total educational attainment were assessed during young
      adulthood. RESULTS: Hierarchical linear modeling revealed that receptive language
      did not differ between the groups at the initial assessment point in childhood;
      however, a significant group by time interaction was observed across development
      with abused females (1) acquiring receptive language at a significantly slower
      rate throughout development and (2) achieving a lower overall maximum level of
      proficiency. Significant differences in receptive language scores emerged as
      early as midadolescence. In addition, abused females reported significantly lower
      rates of high school graduation and lower overall educational attainment when
      compared with their nonabused peers. CONCLUSIONS: Exposure to childhood sexual
      abuse may be a significant risk factor for cognitive performance and achievement
      deficits for victims. These findings have particular public health relevance
      given the high prevalence of sexual abuse and that poor cognitive functioning and
      low levels of educational attainment can contribute to continued adversity
      throughout the life course. Early intervention may assist victims in improving
      cognitive functioning, altering deleterious trajectories, and promoting greater
      life successes.

PMID- 20696732
TI  - Neonatal cerebral sinovenous thrombosis: sifting the evidence for a diagnostic
      plan and treatment strategy.
AB  - Although cerebral sinovenous thrombosis (CSVT) is an uncommon disorder in
      neonates, the incumbent morbidity, mortality, and adverse neurodevelopmental
      sequelae highlight the importance of establishing an early diagnosis with an
      appropriate therapeutic plan. The clinical signs and symptoms of the condition
      are subtle and invariably masquerade under the umbrella of a broad spectrum of
      neonatal illnesses. A high index of diagnostic suspicion is essential for
      investigating and initiating treatment in a timely fashion before major
      complications ensue. Recent advances in accessible radiographic techniques with
      reduced radiation exposure have facilitated rapid diagnosis of thrombosis in both
      the superficial and deep plexuses of the cerebral venous systems. The absence of
      large-scale randomized trials and solid prospective smaller-sample-sized studies
      of neonates with CSVT has compromised our ability to develop efficacious
      treatment decisions. In this review of the scientific literature we offer
      understanding of the complex etiology of CSVT and inherent problems involved in
      the diagnosis and treatment of the disorder and focus on the limitations in
      current follow-up. An approach to neonatal CSVT is proposed on the basis of the
      available evidence from guidelines, registries, prospective and retrospective
      infant studies, and case series.

PMID- 20696733
TI  - Feeding dysfunction in children with eosinophilic gastrointestinal diseases.
AB  - OBJECTIVES: Feeding dysfunction (FD) seen in younger children with eosinophilic
      gastrointestinal disease (EGID) has not been well described. Thus, our aim was to
      further characterize FD in children with EGIDs. METHODS: A retrospective medical
      record analysis of 200 children seen over 12 months in a multidisciplinary
      Gastrointestinal Eosinophilic Diseases Program was performed. The clinical data
      of 33 children identified as also having FD were examined, including information
      obtained by history, physical examination, feeding evaluation, review of
      nutritional data, allergy testing and histologic assessment of mucosal biopsies.
      RESULTS: Of 200 children with EGIDs, 16.5% had significant FD. The median age of
      this group was 34 months (range: 14-113 months). A variety of learned maladaptive
      feeding behaviors were reported in 93.9%. Frequent gagging or vomiting occurred
      in 84.8%. Food sensitivity was documented in 88% while 52% had other allergic
      disease. Twenty one percent were diagnosed with failure to thrive and 69.7%
      required individual or group feeding therapy. Forty-two percent had residual
      eosinophilia of >15 per HPF on esophageal biopsies performed at the time of
      symptoms. CONCLUSIONS: FD is prevalent in children with EGIDs often presenting as
      maladaptive learned feeding behaviors with altered mealtime dynamics and physical
      difficulties in eating mechanics. FD can persist even after eosinophilic
      inflammation is successfully treated. Awareness of the increased prevalence of FD
      in children with EGIDs with enable earlier recognition of this problem, resulting
      in a comprehensive, individualized treatment plan with the desired outcome of
      improving the development, feeding, and nutrition of these children.

PMID- 20696734
TI  - MASiVE: Mapping and Analysis of Sirevirus Elements in plant genome sequences.
AB  - We present MASiVE, an expertly built tool for the large-scale, yet sensitive and
      highly accurate, discovery, preliminary analysis and insertion age estimation of
      intact Sirevirus LTR-retrotransposons in plant genomic sequences. Validation was
      based on the recently available and annotated large maize chromosome one. Results
      show a considerable improvement in the annotation of Sireviruses, and support our
      approach as an important addition to the bioinformatics toolbox of plant
      biologists. AVAILABILITY: PERL source code and essential files are available
      online at http://bat.ina.certh.gr/tools/masive/. The freely available Vmatch,
      LTRharvest, Wise2, and MAFFT algorithms are required.

PMID- 20696735
TI  - The misuse of terms in scientific literature.

PMID- 20696736
TI  - An alignment-free model for comparison of regulatory sequences.
AB  - MOTIVATION: Some recent comparative studies have revealed that regulatory regions
      can retain function over large evolutionary distances, even though the DNA
      sequences are divergent and difficult to align. It is also known that such
      enhancers can drive very similar expression patterns. This poses a challenge for
      the in silico detection of biologically related sequences, as they can only be
      discovered using alignment-free methods. RESULTS: Here, we present a new
      computational framework called Regulatory Region Scoring (RRS) model for the
      detection of functional conservation of regulatory sequences using predicted
      occupancy levels of transcription factors of interest. We demonstrate that our
      model can detect the functional and/or evolutionary links between some non
      alignable enhancers with a strong statistical significance. We also identify
      groups of enhancers that are likely to be similarly regulated. Our model is
      motivated by previous work on prediction of expression patterns and it can
      capture similarity by strong binding sites, weak binding sites and even the
      statistically significant absence of sites. Our results support the hypothesis
      that weak binding sites contribute to the functional similarity of sequences. Our
      model fills a gap between two families of models: detailed, data-intensive models
      for the prediction of precise spatio-temporal expression patterns on the one
      side, and crude, generally applicable models on the other side. Our model borrows
      some of the strengths of each group and addresses their drawbacks. AVAILABILITY:
      The RRS source code is freely available upon publication of this manuscript:
      http://www2.warwick.ac.uk/fac/sci/systemsbiology/staff/ott/tools_and_software/rrs

PMID- 20696737
TI  - 'Heated political dynamics exist ...': examining the politics of palliative care
      in rural British Columbia, Canada.
AB  - Palliative care is delivered by a number of professional groups and informal
      providers across a range of settings. This arrangement works well in that it
      maximizes avenues for providing care, but may also bring about complicated
      'politics' due to struggles over control and decision-making power. Thirty-one
      interviews conducted with formal and informal palliative care providers in a
      rural region of British Columbia, Canada, are drawn upon as a case study. Three
      types of politics impacting on palliative care provision are identified: inter
      community, inter-site, and inter-professional. Three themes crosscut these
      politics: ownership, entitlement, and administration. The politics revealed by
      the interviews, and heretofore underexplored in the palliative literature, have
      implications for the delivery of palliative care. For example, the outcomes of
      the politics simultaneously facilitate (e.g. by promoting advocacy for local
      services) and serve as a barrier to (e.g. by privileging certain communities/care
      sites/provider) palliative care provision.

PMID- 20696738
TI  - Double ECMO in severe ARDS: report of an outstanding case and literature review.
AB  - We report on a 49-year-old male patient who suffered from severe herpes simplex
      (HSV) pneumonia after a fall-from-height injury, causing a circumscript type B
      aortic dissection.The subsequent occurrence of ARDS required a veno-venous ECMO
      circuit that was upgraded to a veno-arterial system due to further oxygenation
      deficits. Following continued respiratory deterioration, the ECMO system already
      in place had to be complemented by a second veno-arterial line. After the onset
      of recovery and because of a developing of a disseminated intravasal coagulation,
      the double ECMO circuit was replaced by a pumpless extracorporeal lung assist
      system (PECLA). The patient recovered completely under systemic virostatic
      therapy.

PMID- 20696739
TI  - A new real-time and precision capnography for human respiration carbon dioxide
      concentration.
AB  - This paper is a description of the designing of a new mainstream device to
      measure human respiration carbon dioxide concentration, based on non-dispersive
      infrared (NDIR) absorption technology. The device can be used to accurately
      monitor the cardiopulmonary status during anaesthesia and mechanical ventilation
      in real time. This new device can not only make up the error of real-time gas
      measurement of the side-stream device, but also make up the accuracy of the main
      stream device. In the paper, four issues which can affect the measurement
      accuracy were considered: respiration gas flow, turbulence of the light source
      with all ranges of wavelength, temperature drift and signal noise. The
      experimental results showed that the device could produce a stable output signal
      and deviation of measurement accuracy could be achieved to within 4%.

PMID- 20696740
TI  - Longitudinal outcomes of a comprehensive, incentivized worksite wellness program.
AB  - This study evaluated health benefits of long-term participation in an employer
      based wellness program, focusing on selected chronic disease risk factors. A
      repeated measures longitudinal time-series study was conducted of 8 years of
      existing prospectively collected annual data, including clinical measures of
      weight, blood pressure, cholesterol, and body fat percent. Participants were
      divided into their risk levels at baseline. Outcomes were compared to level of
      participation, for which annual points earned was a surrogate. Participants had
      lower increases in body mass index (BMI) than the general population had during
      the same time period. Greatest improvements in BMI, blood pressure, and
      cholesterol were seen in those at highest risk levels at baseline and in those
      whose physical activity increased over time. It was found that long-term
      participation in this program improved BMI, blood pressure, and cholesterol. Most
      benefits were found for those in high-risk groups. This program should recruit
      more employees in high health risk categories and emphasize retention and
      increased levels of participation.

PMID- 20696741
TI  - Designing a prospective study when randomization is not feasible.
AB  - When conducting a randomized controlled trial (RCT) is unfeasible, the goal is to
      replicate the randomization process by creating a control group that is
      essentially equivalent to the treatment group on known pre-intervention
      characteristics and assume that the remaining unknown characteristics will not
      bias the results. The strategies proposed in this article are based on the thesis
      that since only pre-intervention characteristics are used for adjustment, a
      comparable control group can be established as soon as the participant group is
      identified. Consequently, outcomes can be observed immediately after launching
      the initiative rather than waiting until study completion. The benefit is that
      significant treatment effects can be observed as they occur, or alternatively,
      the initiative can be cancelled if treatment effects are not attained by a
      certain time point. Although these methods can never ensure the same level of
      validity as in an RCT, they are considered robust alternatives when randomization
      is impractical, and therefore a compelling study design for many commercial
      initiatives, such as disease management programs, benefit design changes, and pay
      for-performance efforts. An obvious constraint is that treated participants must
      first be identified before suitable controls can be found. The preferred strategy
      is to enroll the entire treatment group within a narrow time frame. An
      alternative option is to have periodic enrollment periods with their respective
      treatment and control cohorts. The concept proposed in this article is intended
      to offer a robust alternative to the inadequate strategies currently being used
      in many health care settings where study findings may not be trusted, and thus
      decision makers remain uninformed as to whether an initiative is worth continuing
      or cancelled.

PMID- 20696742
TI  - A qualitative case study of policy maker views about the protection of children
      from smoking in cars.
AB  - INTRODUCTION: As little is known about the policy making process around smokefree
      car laws, we aimed to investigate policy makers' views about such laws in a
      setting where these have not yet been enacted but where published evidence exists
      on the hazard of smoking in cars and on relevant public support. METHODS: A New
      Zealand (NZ) case study (of the NZ health policy community) used documents and
      qualitative in-depth interviews with 62 national-level and District Health Board
      (DHB)-level policy makers (during 2008-2009). Forty were government or
      nongovernmental organization officials, 5 DHB board members, and 17 Members of
      Parliament. RESULTS: We found very strong themes of policy maker concern for the
      vulnerability of children and the need for their protection from secondhand
      smoke. There were mixed reactions to the idea of a smokefree law for cars with
      children in them. These themes and mixed reactions spanned both the "left" and
      "right" political parties. The evidence indicates that smokefree car laws are
      only barely on the NZ national policy making agenda. They are generally not seen
      as politically attractive, as effective, or easy to implement. DISCUSSION: In
      this particular policy setting, there appear to have been assumptions by policy
      makers about the dominance of adult "privacy" over child protection. The lack of
      awareness in this particular (NZ) policy community of national-level public
      support for banning smoking in cars with children and of the progress elsewhere
      on such laws also suggests the importance of information and advocacy if such
      laws are to be progressed.

PMID- 20696743
TI  - Doctor shortage and chronic underfunding spark crisis in Israel's public
      hospitals.

PMID- 20696744
TI  - State of Virginia launches legal challenge to US health reforms.

PMID- 20696745
TI  - A chemically modified alpha-amylase with a molten-globule state has entropically
      driven enhanced thermal stability.
AB  - The thermostability properties of TAA were investigated by chemically modifying
      carboxyl groups on the surface of the enzyme with AMEs. The TAA(MOD) exhibited a
      200% improvement in starch-hydrolyzing productivity at 60 degrees C. By studying
      the kinetic, thermodynamic and biophysical properties, we found that TAA(MOD) had
      formed a thermostable, MG state, in which the unfolding of the tertiary structure
      preceded that of the secondary structure by at least 20 degrees C. The X-ray
      crystal structure of TAA(MOD) revealed no new permanent interactions
      (electrostatic or other) resulting from the modification. By deriving
      thermodynamic activation parameters of TAA(MOD), we rationalised that
      thermostabilisation have been caused by a decrease in the entropy of the
      transition state, rather than being enthalpically driven. Far-UV CD shows that
      the origin of decreased entropy may have arisen from a higher helical content of
      TAA(MOD). This study provides new insight into the intriguing properties of an MG
      state resulting from the chemical modification of TAA.

PMID- 20696746
TI  - A Patient's Journey. At sixes and sevens: prostate cancer.

PMID- 20696747
TI  - Managing urinary incontinence in older people.

PMID- 20696748
TI  - Scottish government is forced to consider alternatives to minimum alcohol price.

PMID- 20696749
TI  - Life expectancy in Scotland remains lower than in many EU countries.

PMID- 20696750
TI  - Venous obstruction and cerebral perfusion during experimental cardiopulmonary
      bypass.
AB  - To investigate the effects on cerebral perfusion by experimental venous
      congestion of the superior vena cava (SVC) during bicaval cardiopulmonary bypass
      (CPB) at 34  degrees C, pigs were subjected to SVC obstruction at levels of 75%,
      50%, 25% and 0% of baseline SVC flow at two arterial flow levels (low, LQ, high,
      HQ). The cerebral perfusion was examined with near-infrared spectroscopy (NIRS),
      cerebral microdialysis and blood gas analysis. SVC obstruction caused significant
      decreases in the NIRS tissue oxygenation index (TOI) and in SVC oxygen
      saturations (P<0.05, both groups), while the mixed venous saturation was
      decreased only in the LQ group. Sagittal sinus venous saturations were measured
      in the HQ group and found significantly reduced in response to venous congestion
      (P<0.05). No microdialysis changes were seen at the group level, however,
      individual ischemic patterns in terms of concomitant venous desaturation,
      decreased TOI and increased lactate/pyruvate occurred in both groups. The total
      venous drainage remained stabile throughout the experiment, indicating increased
      flow in the inferior vena cava cannula. The results indicate that SVC congestion
      may impair cerebral perfusion especially in the case of compromised arterial flow
      during CPB. Reduced SVC cannula flow may pass undetected during bicaval CPB, if
      SVC flow is not specifically monitored.

PMID- 20696751
TI  - Different aspects of atrial fibrillation genetics.
AB  - Atrial fibrillation (AF) is a consequence of a complex interplay of genetic,
      epigenetic and environmental factors. In addition, AF is a major contributor to
      stroke, heart failure, and mortality. Several family studies have shown a strong
      polygenetic predisposition for AF but, so far, most of the linkage analysis and
      candidate gene studies have discovered only monogenic, rare, deleterious
      mutations. While research in human genetics has moved from monogenic to
      oligogenic to complex diseases, its pharmacogenetics branch has followed, usually
      a few years behind. The present paper reviews the potential contributions of
      genetic approaches to AF.

PMID- 20696752
TI  - Loss of miR-200c expression induces an aggressive, invasive, and chemoresistant
      phenotype in non-small cell lung cancer.
AB  - The development of metastases is the main reason for cancer-related death in non
      small cell lung cancer (NSCLC). The initiation of metastasis involves an increase
      in cell motility mediated by the loss of cell-cell adhesion caused by E-cadherin
      repression, in a process commonly known as epithelial-to-mesenchymal transition.
      A role for microRNA-200 family members in regulating epithelial-to-mesenchymal
      transition has recently been indicated but data about their expression in lung
      tumors is still unavailable. The present study investigated the expression of miR
      200c in a panel of NSCLC cell lines (n = 9), and a strong inverse correlation
      with invasion was detected. Reintroduction of miR-200c into highly
      invasive/aggressive NSCLC cells induced a loss of the mesenchymal phenotype by
      restoring E-cadherin and reducing N-cadherin expression, and inhibited in vitro
      cell invasion as well as in vivo metastasis formation. Moreover, miR-200c
      overexpression restored the sensitivity of NCI-H1299 cells to cisplatin and
      cetuximab. Hypermethylation of the promoter region was found to be responsible
      for the loss of miR-200c in invasive cells, as evaluated by 5-aza-2'
      deoxycytidine treatment, methylation-specific PCR, and bisulfite sequencing. In
      primary tumor specimens obtained from 69 patients with consecutively resected
      NSCLC, lower miR-200c expression levels were found to be associated with a poor
      grade of differentiation (P = 0.04), a higher propensity to lymph node metastases
      (P < 0.01), and with a lower E-cadherin expression (P = 0.01). These data
      indicate that the loss of miR-200c expression induces an aggressive, invasive,
      and chemoresistant phenotype, and that assessment of its expression could
      contribute to a better clinicopathologic definition of patients with NSCLC.

PMID- 20696753
TI  - Introducing family medicine in a pluralistic health care system: how patients and
      doctors see it.
AB  - BACKGROUND: The health care systems in many countries are focused on specialist
      care. In those countries that have recently changed to a primary care-based
      system, some doctors and patients were dissatisfied with the change. OBJECTIVE:
      To explore the opinions of the general public and the doctors on the change to a
      family medicine (FM)-based health care system. METHODS: Qualitative study with
      focus groups of doctors working in different practice settings. Quantitative
      study with questionnaires sent to all doctors registered in Hong Kong and a
      telephone survey targeting the general public aged >=18. RESULTS: Doctors in the
      focus groups generally supported a FM-based health care system. They were
      concerned that there were not enough family doctors for such a system and the
      patients' current free choice of any doctor for primary care would impede its
      success. Thousand six hundred and forty-seven adults took part in the telephone
      survey (response rate 67.6%) and 2310 doctors (22.8%) responded to the
      questionnaire. Nearly 95% of the general public respondents agreed to the FM
      system though only 66.3% of them had ever heard of the term family doctor. About
      65% of the doctors supported this system but only 33% agreed that the system
      would work. The specialist-doctors were less supportive of mandatory referral
      than the non-specialists, while the public was equally divided on this issue.
      CONCLUSIONS: The public accepts the FM-based system but needs education on the
      benefits of primary health care. Direct access to the specialist would be the
      greatest barrier. Government involvements are essential for the reform.

PMID- 20696754
TI  - Does vocational training in family medicine have an impact on antibiotic
      prescribing pattern?
AB  - BACKGROUND: Antibiotics overuse is common and is the major cause of antibiotic
      resistance. Rational use of antibiotics by GPs is essential as most health
      problems are exclusively dealt within primary care. Postgraduate family medicine
      (FM) training has become established in various countries over the last few
      decades but little is known about the effect of FM training on antibiotic
      prescribing. OBJECTIVE: To determine whether GPs with FM training prescribe less
      antibiotics than those without training. METHODS: GPs working in a pluralistic
      primary health care system took part in the 2007-08 primary care morbidity and
      management survey in Hong Kong and collected information of all consecutive
      patient encounters during predetermined weeks of data collection. Characteristics
      of GPs, training status, patient morbidity and antibiotic prescribing pattern
      were compared using multivariate regression analyses. RESULTS: One hundred and
      nine GPs, of whom 67 had FM training, participated in the study and recorded 69
      973 health problems. The overall antibiotic prescribing rate was 8.5% and that of
      GPs with FM training was 5.4% compared with the 13.3% among those without.
      Multivariate logistic regression showed that GPs with FM training were less
      likely to prescribe antibiotics (odds ratio 0.68, P < 0.05). They had lower
      antibiotic prescribing rates when managing upper respiratory tract infections,
      acute bronchitis and cough but higher in treating infective conjunctivitis and
      acute laryngitis. CONCLUSIONS: Postgraduate FM training in Hong Kong is
      associated with significantly lower antibiotic prescribing rates. This supports
      the importance of FM training in rationalizing the use of antibiotics in Hong
      Kong.

PMID- 20696755
TI  - Increased attendance rate: BMI matters, lifestyles don't. Results from the Dutch
      SMILE study.
AB  - INTRODUCTION: a small group of frequent attenders is responsible for a
      disproportional large percentage of all daytime consultations in general
      practice. High attendance rates are related to demographic and psychological
      characteristics. Differences in attendance rates are only partly explained by
      chronic diseases. Furthermore, lifestyles might be relevant too. The aim of this
      study was to examine the effect of lifestyle on attendance rates. METHOD: this
      study is part of the Study of Medical Information and Lifestyles in Eindhoven,
      the Netherlands (SMILE). Generalized estimated equations were used to determine
      the relation between attendance rate and the different lifestyle factors (N =
      4444). RESULTS: a higher body mass index was related to increased attendance rate
      in both male [relative risk (RR) 1.02; 95% confidence interval (CI) 1.01-1.03]
      and female patients (RR 1.01; 95% CI 1.01-1.02). Lifestyles were not related to
      the attendance rate, except for a sedentary lifestyle in women (RR 1.08; 95% CI
      1.04-1.12). DISCUSSION: since half of the Dutch population suffers from
      overweight or obesity and this number is still increasing, attendance rates will
      rise further. In order to relieve the GPs, nurse practitioners could play a more
      prominent role in lifestyle interventions concerning overweight and obesity and
      its related diseases.

PMID- 20696756
TI  - Mechanism of regulation of native cardiac muscle thin filaments by rigor cardiac
      myosin-S1 and calcium.
AB  - We have studied the mechanism of activation of native cardiac thin filaments by
      calcium and rigor myosin. The acceleration of the rate of 2'-deoxy-3'-O-(N
      methylanthraniloyl)ADP (mdADP) dissociation from cardiac myosin-S1-mdADP-P(i) and
      cardiac myosin-S1-mdADP by native cardiac muscle thin filaments was measured
      using double mixing stopped-flow fluorescence. Relative to inhibited thin
      filaments (no bound calcium or rigor S1), fully activated thin filaments (with
      both calcium and rigor-S1 bound) increase the rate of product dissociation from
      the physiologically important pre-power stroke myosin-mdADP-P(i) by a factor of
      ~75. This can be compared with only an ~6-fold increase in the rate of nucleotide
      diphosphate dissociation from nonphysiological myosin-mdADP by the fully
      activated thin filaments relative to the fully inhibited thin filaments. These
      results show that physiological levels of regulation are not only dependent on
      the state of the thin filament but also on the conformation of the myosin. Less
      than 2-fold regulation is due to a change in affinity of myosin-ADP-P(i) for thin
      filaments such as would be expected by a simple "steric blocking" of the myosin
      binding site of the thin filament by tropomyosin. Although maximal activation
      requires both calcium and rigor myosin-S1 bound to the cardiac filament,
      association with a single ligand produces ~70% maximal activation. This can be
      contrasted with skeletal thin filaments in which calcium alone only activated the
      rate of product dissociation ~20% of maximum, and rigor myosin produces ~30%
      maximal activation.

PMID- 20696757
TI  - Inhibition of cell migration and cell division correlates with distinct effects
      of microtubule inhibiting drugs.
AB  - Drugs that target microtubules are thought to inhibit cell division and cell
      migration by suppressing dynamic instability, a "search and capture" behavior
      that allows microtubules to probe their environment. Here, we report that
      subtoxic drug concentrations are sufficient to inhibit plus-end microtubule
      dynamic instability and cell migration without affecting cell division or
      microtubule assembly. The higher drug concentrations needed to inhibit cell
      division act through a novel mechanism that generates microtubule fragments by
      stimulating microtubule minus-end detachment from their organizing centers. The
      frequency of microtubule detachment in untreated cells increases at prophase
      suggesting that it is a regulated cellular process important for spindle assembly
      and function. We conclude that drugs produce differential dose-dependent effects
      at microtubule plus and minus-ends to inhibit different microtubule-mediated
      functions.

PMID- 20696758
TI  - Clostridium difficile toxin A decreases acetylation of tubulin, leading to
      microtubule depolymerization through activation of histone deacetylase 6, and
      this mediates acute inflammation.
AB  - Clostridium difficile toxin A is known to cause actin disaggregation through the
      enzymatic inactivation of intracellular Rho proteins. Based on the rapid and
      severe cell rounding of toxin A-exposed cells, we speculated that toxin A may be
      involved in post-translational modification of tubulin, leading to microtubule
      instability. In the current study, we observed that toxin A strongly reduced
      alpha-tubulin acetylation in human colonocytes and mouse intestine. Fractionation
      analysis demonstrated that toxin A-induced alpha-tubulin deacetylation yielded
      monomeric tubulin, indicating the presence of microtubule depolymerization.
      Inhibition of the glucosyltransferase activity against Rho proteins of toxin A by
      UDP-2',3'-dialdehyde significantly abrogated toxin A-induced alpha-tubulin
      deacetylation. In colonocytes treated with trichostatin A (TSA), an inhibitor of
      the HDAC6 tubulin deacetylase, toxin A-induced alpha-tubulin deacetylation and
      loss of tight junction were completely blocked. Administration of TSA also
      attenuated proinflammatory cytokine production, mucosal damage, and epithelial
      cell apoptosis in mouse intestine exposed to toxin A. These results suggest that
      toxin A causes microtubule depolymerization by activation of HDAC6-mediated
      tubulin deacetylation. Indeed, blockage of HDAC6 by TSA markedly attenuates alpha
      tubulin deacetylation, proinflammatory cytokine production, and mucosal damage in
      a toxin A-induced mouse enteritis model. Tubulin deacetylation is an important
      component of the intestinal inflammatory cascade following toxin A-mediated Rho
      inactivation in vitro and in vivo.

PMID- 20696759
TI  - A lethal de novo mutation in the middle domain of the dynamin-related GTPase Drp1
      impairs higher order assembly and mitochondrial division.
AB  - Mitochondria dynamically fuse and divide within cells, and the proper balance of
      fusion and fission is necessary for normal mitochondrial function, morphology,
      and distribution. Drp1 is a dynamin-related GTPase required for mitochondrial
      fission in mammalian cells. It harbors four distinct domains: GTP-binding,
      middle, insert B, and GTPase effector. A lethal mutation (A395D) within the Drp1
      middle domain was reported in a neonate with microcephaly, abnormal brain
      development, optic atrophy, and lactic acidemia (Waterham, H. R., Koster, J., van
      Roermund, C. W., Mooyer, P. A., Wanders, R. J., and Leonard, J. V. (2007) N.
      Engl. J. Med. 356, 1736-1741). Mitochondria within patient-derived fibroblasts
      were markedly elongated, but the molecular mechanisms underlying these findings
      were not demonstrated. Because the middle domain is particularly important for
      the self-assembly of some dynamin superfamily proteins, we tested the hypothesis
      that this A395D mutation, and two other middle domain mutations (G350D, G363D)
      were important for Drp1 tetramerization, higher order assembly, and function.
      Although tetramerization appeared largely intact, each of these mutations
      compromised higher order assembly and assembly-dependent stimulation of Drp1
      GTPase activity. Moreover, mutant Drp1 proteins exhibited impaired localization
      to mitochondria, indicating that this higher order assembly is important for
      mitochondrial recruitment, retention, or both. Overexpression of these middle
      domain mutants markedly inhibited mitochondrial division in cells. Thus, the Drp1
      A395D lethal defect likely resulted in impaired higher order assembly of Drp1 at
      mitochondria, leading to decreased fission, elongated mitochondria, and altered
      cellular distribution of mitochondria.

PMID- 20696760
TI  - Dyrk1A phosphorylates p53 and inhibits proliferation of embryonic neuronal cells.
AB  - Down syndrome (DS) is associated with many neural defects, including reduced
      brain size and impaired neuronal proliferation, highly contributing to the mental
      retardation. Those typical characteristics of DS are closely associated with a
      specific gene group "Down syndrome critical region" (DSCR) on human chromosome
      21. Here we investigated the molecular mechanisms underlying impaired neuronal
      proliferation in DS and, more specifically, a regulatory role for dual
      specificity tyrosine-(Y) phosphorylation-regulated kinase 1A (Dyrk1A), a DSCR
      gene product, in embryonic neuronal cell proliferation. We found that Dyrk1A
      phosphorylates p53 at Ser-15 in vitro and in immortalized rat embryonic
      hippocampal progenitor H19-7 cells. In addition, Dyrk1A-induced p53
      phosphorylation at Ser-15 led to a robust induction of p53 target genes (e.g.
      p21(CIP1)) and impaired G(1)/G(0)-S phase transition, resulting in attenuated
      proliferation of H19-7 cells and human embryonic stem cell-derived neural
      precursor cells. Moreover, the point mutation of p53-Ser-15 to alanine rescued
      the inhibitory effect of Dyrk1A on neuronal proliferation. Accordingly, brains
      from embryonic DYRK1A transgenic mice exhibited elevated levels of Dyrk1A, Ser-15
      (mouse Ser-18)-phosphorylated p53, and p21(CIP1) as well as impaired neuronal
      proliferation. These findings suggest that up-regulation of Dyrk1A contributes to
      altered neuronal proliferation in DS through specific phosphorylation of p53 at
      Ser-15 and subsequent p21(CIP1) induction.

PMID- 20696761
TI  - A new Kv1.2 channelopathy underlying cerebellar ataxia.
AB  - A forward genetic screen of mice treated with the mutagen ENU identified a mutant
      mouse with chronic motor incoordination. This mutant, named Pingu (Pgu), carries
      a missense mutation, an I402T substitution in the S6 segment of the voltage-gated
      potassium channel Kcna2. The gene Kcna2 encodes the voltage-gated potassium
      channel alpha-subunit Kv1.2, which is abundantly expressed in the large axon
      terminals of basket cells that make powerful axo-somatic synapses onto Purkinje
      cells. Patch clamp recordings from cerebellar slices revealed an increased
      frequency and amplitude of spontaneous GABAergic inhibitory postsynaptic currents
      and reduced action potential firing frequency in Purkinje cells, suggesting that
      an increase in GABA release from basket cells is involved in the motor
      incoordination in Pgu mice. In line with immunochemical analyses showing a
      significant reduction in the expression of Kv1 channels in the basket cell
      terminals of Pgu mice, expression of homomeric and heteromeric channels
      containing the Kv1.2(I402T) alpha-subunit in cultured CHO cells revealed subtle
      changes in biophysical properties but a dramatic decrease in the amount of
      functional Kv1 channels. Pharmacological treatment with acetazolamide or
      transgenic complementation with wild-type Kcna2 cDNA partially rescued the motor
      incoordination in Pgu mice. These results suggest that independent of known
      mutations in Kcna1 encoding Kv1.1, Kcna2 mutations may be important molecular
      correlates underlying human cerebellar ataxic disease.

PMID- 20696762
TI  - Critical role of 7,8-didemethyl-8-hydroxy-5-deazariboflavin for photoreactivation
      in Chlamydomonas reinhardtii.
AB  - DNA photolyases use two noncovalently bound chromophores to catalyze
      photoreactivation, the blue light-dependent repair of DNA that has been damaged
      by ultraviolet light. FAD is the catalytic chromophore for all photolyases and is
      essential for photoreactivation. The identity of the second chromophore is often
      7,8-didemethyl-8-hydroxy-5-deazariboflavin (FO). Under standard light conditions,
      the second chromophore is considered nonessential for photoreactivation because
      DNA photolyase bound to only FAD is sufficient to catalyze the repair of UV
      damaged DNA. phr1 is a photoreactivation-deficient strain of Chlamydomonas. In
      this work, the PHR1 gene of Chlamydomonas was cloned through molecular mapping
      and shown to encode a protein similar to known FO synthases. Additional results
      revealed that the phr1 strain was deficient in an FO-like molecule and that this
      deficiency, as well as the phr1 photoreactivation deficiency, could be rescued by
      transformation with DNA constructs containing the PHR1 gene. Furthermore,
      expression of a PHR1 cDNA in Escherichia coli produced a protein that generated a
      molecule with characteristics similar to FO. Together, these results indicate
      that the Chlamydomonas PHR1 gene encodes an FO synthase and that optimal
      photoreactivation in Chlamydomonas requires FO, a molecule known to serve as a
      second chromophore for DNA photolyases.

PMID- 20696763
TI  - Modulation of agrin-induced acetylcholine receptor clustering by extracellular
      signal-regulated kinases 1 and 2 in cultured myotubes.
AB  - Agrin released by motoneurons induces and/or maintains acetylcholine receptor
      (AChR) clustering and other aspects of postsynaptic differentiation at the
      vertebrate neuromuscular junction. Agrin acts by binding and activating a
      receptor complex containing LDL receptor protein 4 (Lrp4) and muscle-specific
      kinase (MuSK). Two critical downstream components of this signaling cascade, Dox
      7 and rapsyn, have been identified. However, additional intracellular essential
      elements remain unknown. Prior observations by others and us suggested
      antagonistic interactions between agrin and neuregulin-1 (Nrg-1) signaling in
      cultured myotubes and developing muscle fibers in vivo. A hallmark of Nrg-1
      signaling in skeletal muscle cells is the activation of extracellular signal
      regulated kinases 1 and 2 (ERK1/2). ERK1/2 are also activated in most cells by
      phorbol 12-myristate 13-acetate, a classical inhibitor of agrin-induced AChR
      clustering in myotubes. Here, it was investigated whether agrin activates ERK1/2
      directly and whether such activation modulates agrin-induced AChR clustering.
      Agrin induced a rapid but transient activation of ERK1/2 in myotubes that was
      Lrp4/MuSK-dependent. However, blocking this ERK1/2 activation did not prevent but
      potentiated AChR clustering induced by agrin. ERK1/2 activation was dispensable
      for Nrg-1-mediated inhibition of the AChR clustering activity of agrin, but was
      indispensable for such activity by phorbol 12-myristate 13-acetate. Together,
      these results suggest agrin-induced activation of ERK1/2 is a negative modulator
      of agrin signaling in skeletal muscle cells.

PMID- 20696764
TI  - The Lbc Rho guanine nucleotide exchange factor alpha-catulin axis functions in
      serotonin-induced vascular smooth muscle cell mitogenesis and RhoA/ROCK
      activation.
AB  - Serotonin (5-hydroxytryptamine, 5-HT) is mitogenic for several cell types
      including pulmonary arterial smooth muscle cells (PASMC), and is associated with
      the abnormal vascular smooth muscle remodeling that occurs in pulmonary arterial
      hypertension. RhoA/Rho kinase (ROCK) function is required for 5-HT-induced PASMC
      mitogenesis, and 5-HT activates RhoA; however, the signaling steps are poorly
      defined. Rho guanine nucleotide exchange factors (Rho GEFs) transduce
      extracellular signals to Rho, and we found that 5-HT treatment of PASMC led to
      increased membrane-associated Lbc Rho GEF, suggesting modulation by 5-HT. Lbc
      knockdown by siRNA attenuated 5-HT-induced thymidine uptake in PASMC, indicating
      a role in PASMC mitogenesis. 5-HT triggered Rho-dependent serum response factor
      mediated reporter activation in PASMC, and this was reduced by Lbc depletion. Lbc
      knockdown reduced 5-HT-induced RhoA/ROCK activation, but not p42/44 ERK MAP
      kinase activation, suggesting that Lbc is an intermediary between 5-HT and
      RhoA/ROCK, but not ERK. 5-HT stimulation of PASMC led to increased association
      between Lbc, RhoA, and the alpha-catulin scaffold. Furthermore, alpha-catulin
      knockdown attenuated 5-HT-induced PASMC thymidine uptake. 5-HT-induced PASMC
      mitogenesis was reduced by dominant-negative G(q) protein, suggesting cooperation
      with Lbc/alpha-catulin. These results for the first time define a Rho GEF
      involved in vascular smooth muscle cell growth and serotonin signaling, and
      suggest that Lbc Rho GEF family members play distinct roles. Thus, the Lbc/alpha
      catulin axis participates in 5-HT-induced PASMC mitogenesis and RhoA/ROCK
      signaling, and may be an interventional target in diseases involving vascular
      smooth muscle remodeling.

PMID- 20696766
TI  - Nucleoplasmin binds histone H2A-H2B dimers through its distal face.
AB  - Nucleoplasmin (NP) is a pentameric chaperone that regulates the condensation
      state of chromatin extracting specific basic proteins from sperm chromatin and
      depositing H2A-H2B histone dimers. It has been proposed that histones could bind
      to either the lateral or distal face of the pentameric structure. Here, we
      combine different biochemical and biophysical techniques to show that natural,
      hyperphosphorylated NP can bind five H2A-H2B dimers and that the amount of bound
      ligand depends on the overall charge (phosphorylation level) of the chaperone.
      Three-dimensional reconstruction of NP/H2A-H2B complex carried out by electron
      microscopy reveals that histones interact with the chaperone distal face. Limited
      proteolysis and mass spectrometry indicate that the interaction results in
      protection of the histone fold and most of the H2A and H2B C-terminal tails. This
      structural information can help to understand the function of NP as a histone
      chaperone.

PMID- 20696765
TI  - Semaphorin 5A and plexin-B3 inhibit human glioma cell motility through
      RhoGDIalpha-mediated inactivation of Rac1 GTPase.
AB  - Semaphorins and plexins are implicated in the progression of various types of
      cancer, although the molecular basis has not been fully elucidated. Here, we
      report the expression of plexin-B3 in glioma cells, which upon stimulation by its
      ligand Sema5A results in significant inhibition of cell migration and invasion. A
      search for the underlying mechanism revealed direct interaction of plexin-B3 with
      RhoGDP dissociation inhibitor alpha (RhoGDIalpha), a negative regulator of
      RhoGTPases that blocks guanine nucleotide exchange and sequesters them away from
      the plasma membrane. Glioma cells challenged with Sema5A indeed showed a marked
      reduction in Rac1-GTP levels by 60%, with a concomitant disruption of
      lamellipodia. The inactivation of Rac1 was corroborated to contribute to the
      impediment of glioma cell invasion by Sema5A, as supported by the abolishment of
      effect upon forced expression of a constitutively active Rac1 mutant.
      Furthermore, silencing the endogenous expression of RhoGDIalpha in glioma cells
      was found to be sufficient in abrogating the down-regulation of Rac1-GTP and the
      ensuing suppression of glioma cell motility induced by Sema5A. Mechanistically,
      we provide evidence that Sema5A promotes Rac1 recruitment to RhoGDIalpha and
      reduces its membrane localization in a plexin-B3-dependent manner, thereby
      preventing Rac1 activation. This represents a novel signaling of semaphorin and
      plexin in the control of cell motility by indirect inactivation of Rac1 through
      RhoGDIalpha.

PMID- 20696767
TI  - Regulation of the matriptase-prostasin cell surface proteolytic cascade by
      hepatocyte growth factor activator inhibitor-1 during epidermal differentiation.
AB  - Matriptase, a membrane-tethered serine protease, plays essential roles in
      epidermal differentiation and barrier function, largely mediated via its
      activation of prostasin, a glycosylphosphatidylinositol-anchored serine protease.
      Matriptase activity is tightly regulated by its inhibitor hepatocyte growth
      factor activator inhibitor-1 (HAI-1) such that free active matriptase is only
      briefly available to act on its substrates. In the current study we provide
      evidence for how matriptase activates prostasin under this tight control by HAI
      1. When primary human keratinocytes are induced to differentiate in a skin
      organotypic culture model, both matriptase and prostasin are constitutively
      activated and then inhibited by HAI-1. These processes also occur in HaCaT human
      keratinocytes when matriptase activation is induced by exposure of the cells to a
      pH 6.0 buffer. Using this acid-inducible activation system we demonstrate that
      prostatin activation is suppressed by matriptase knockdown and by blocking
      matriptase activation with sodium chloride, suggesting that prostatin activation
      is dependent on matriptase in this system. Kinetics studies further reveal that
      the timing of autoactivation of matriptase, prostasin activation, and inhibition
      of both enzymes by HAI-1 binding are closely correlated. These data suggest that,
      during epidermal differentiation, the matriptase-prostasin proteolytic cascade is
      tightly regulated by two mechanisms: 1) prostasin activation temporally coupled
      to matriptase autoactivation and 2) HAI-1 rapidly inhibiting not only active
      matriptase but also active prostasin, resulting in an extremely brief window of
      opportunity for both active matriptase and active prostasin to act on their
      substrates.

PMID- 20696768
TI  - Rod/Zw10 complex is required for PIASy-dependent centromeric SUMOylation.
AB  - SUMO conjugation of cellular proteins is essential for proper progression of
      mitosis. PIASy, a SUMO E3 ligase, is required for mitotic SUMOylation of
      chromosomal proteins, yet the regulatory mechanism behind the PIASy-dependent
      SUMOylation during mitosis has not been determined. Using a series of truncated
      PIASy proteins, we have found that the N terminus of PIASy is not required for
      SUMO modification in vitro but is essential for mitotic SUMOylation in Xenopus
      egg extracts. We demonstrate that swapping the N terminus of PIASy protein with
      the corresponding region of other PIAS family members abolishes chromosomal
      binding and mitotic SUMOylation. We further show that the N-terminal domain of
      PIASy is sufficient for centromeric localization. We identified that the N
      terminal domain of PIASy interacts with the Rod/Zw10 complex, and
      immunofluorescence further reveals that PIASy colocalizes with Rod/Zw10 in the
      centromeric region. We show that the Rod/Zw10 complex interacts with the first 47
      residues of PIASy which were particularly important for mitotic SUMOylation.
      Finally, we show that depletion of Rod compromises the centromeric localization
      of PIASy and SUMO2/3 in mitosis. Together, we demonstrate a fundamental mechanism
      of PIASy to localize in the centromeric region of chromosome to execute
      centromeric SUMOylation during mitosis.

PMID- 20696769
TI  - Risk factors for violence exposure and attributable healthcare costs: results
      from the Danish national health interview surveys.
AB  - AIMS: To describe the characteristics of men and women exposed to physical
      violence, to identify risk factors for violence exposure and to quantify the
      attributable healthcare costs of violence. METHODS: The Danish national health
      interview surveys of 2000 and 2005 included data on exposure to defined forms of
      physical violence over the last 12 months. Respondents who reported exposure to
      violence during the past year were compared with a reference group of non-exposed
      respondents, and data were merged with the National Health Registers. We
      identified risk factors for violence by logistic regression models and used OLS
      regression for quantification of attributable healthcare costs of violence,
      including somatic and psychiatric admissions, outpatient contacts, prescriptions
      and primary health services; and analyzed intimate partner violence separately.
      RESULTS: Young age, being divorced and drinking more than the recommended amount
      of alcohol per week were risk factors for violence both for men and women. Total
      annual healthcare costs, adjusted for age and deliveries, were 787 euros higher
      on average for women exposed to violence than for non-exposed women, mainly
      related to psychiatric treatment. For women, no significant cost differences
      existed between victims of partner violence and non-victims. The total healthcare
      costs were not higher for exposed men than for non-exposed men, but male victims
      of partner violence incurred significantly higher costs. CONCLUSIONS: Primarily
      due to costs of psychiatric treatment, male and female victims of violence had
      higher total healthcare costs than non-exposed people. Whether mental health
      problems increase the risk of violence exposure or violence is a particular risk
      factor for health problems cannot be assessed by cross-sectional data alone.

PMID- 20696770
TI  - Incidence of and risk factors for type-2 diabetes in a general population: the
      Tromso Study.
AB  - AIMS: To determine the gender-specific incidence and risk factors of type-2
      diabetes mellitus (T2DM) in a general population. METHODS: The study is based on
      12,431 men and 13,737 women aged 25-98 years, attending the Tromso Study in 1994
      and followed through 2005, who did not have diabetes when entering the study. Sex
      specific hazard ratios were estimated from Cox proportional hazard models.
      RESULTS: A total of 522 cases of T2DM were registered, 308 among men and 214
      among women. The age-standardised incidence rate was higher in men than in women,
      2.6 (95% CI 2.32-2.90) and 1.6(95% CI 1.40-1.83) per 1000 person-years,
      respectively. In multivariate survival analysis, age, body mass index
      (BMI),triglycerides, high-density lipoprotein (HDL) cholesterol, hypertension,
      family history of diabetes, low education and smoking were independent predictors
      of T2DM in both genders (p<0.05). Total cholesterol and lack of leisure-time
      physical activity were independent predictors in men only. We found an
      interaction between HDL cholesterol and triglyceride levels(p<0.001) and between
      triglyceride levels and a positive family history of diabetes (p=.04). These
      interactions were independent of BMI. A positive family history combined with
      triglycerides in the highest tertile and BMI >25 kg/m(2) conveyed a 10-year risk
      of T2DM of 10% (95% CI 8-12%) vs. 0.2% (95% CI 0.08-0.31%) for the lowest risk
      group. CONCLUSIONS: A family history of diabetes, elevated BMI, and high
      triglyceride levels identifies independent of cardiovascular risk factors, a
      group with especially high risk of T2DM. [corrected]

PMID- 20696771
TI  - Is familial lupus different from sporadic lupus? Data from LUMINA (LXXIII), a
      multiethnic US cohort.
AB  - The aim of this study was to characterize the clinical features of familial
      lupus, and determine its influence on damage accrual and survival using data from
      LUMINA, a longitudinal multiethnic US cohort. Familial lupus was defined as
      patients with a first-degree relative with systemic lupus erythematosus. Relative
      risks were estimated by logistic regression; odds ratios (ORs) and their 95%
      confidence intervals (CIs) were the measure of association for familial lupus.
      Hazard ratios were calculated using Cox proportional hazards adjusted for
      potential confounders for damage and survival. Of 644 patients, 32 had familial
      and 612 had sporadic lupus; both groups were of comparable age (~36 years).
      Patients with familial lupus were, in decreasing order of frequency, siblings,
      parents and children. In multivariable analyses, mucosal ulcers (OR = 1.92, 95%
      CI 0.65-5.70), mitral valve prolapse (OR = 1.74, 95% CI 0.50-6.10),
      cerebrovascular disease (OR = 4.18, 95% CI 0.98-17.76) and oral contraceptive use
      (ever/never; OR = 2.51, 95% CI 0.88-7.19) were more likely in familial lupus, but
      a history of low platelet count (<150,000/mm(3); OR=0.31, 95% CI 0.08-1.17) and
      pulmonary disease activity (OR=0.39, 95% CI 0.14-1.20) were less likely. However,
      none of these associations reached statistical significance. Familial lupus was
      not significantly associated with a shorter time to either damage accrual or
      death (HR = 0.77, 95% CI 0.37-1.59, p = 0.4746 and HR = 0.20, 95% CI 0.03-1.47, p
      = 0.2020, respectively). We conclude that although some clinical differences were
      observed between patients with familial and sporadic lupus, familial lupus was
      not associated with a significantly greater disease burden (damage, survival)
      than sporadic lupus.

PMID- 20696772
TI  - Phosphorylation of estrogen receptor beta at serine 105 is associated with good
      prognosis in breast cancer.
AB  - Estrogen receptor (ER) action is modulated by posttranslational modifications.
      Although ERalpha phosphorylation correlates with patient outcome, ERbeta is
      similarly phosphorylated but its significance in breast cancer has not been
      addressed. We investigated whether ERbeta that is phosphorylated at serine 105
      (S105-ERbeta) is expressed in breast cancer and assessed potential clinical
      implications of this phosphorylation. Following antibody validation, S105-ERbeta
      expression was studied in tissue microarrays comprising 108 tamoxifen-resistant
      and 351 tamoxifen-sensitive cases and analyzed against clinical data. S105-ERbeta
      regulation in vitro was assessed by Western blot, flow cytometry, and
      immunofluorescence. Nuclear S105-ERbeta was observed in breast carcinoma and was
      associated with better survival (Allred score > or =3), even in tamoxifen
      resistant cases, and additionally correlated with ERbeta1 and ERbeta2 expression.
      Distinct S105-ERbeta nuclear speckles were seen in some higher grade tumors. S105
      ERbeta levels increased in MCF-7 cells in response to 17beta-estradiol, the
      ERbeta-specific agonist diarylpropionitrile, and the partial ERbeta-agonist
      genistein. S105-ERbeta nuclear speckles were also seen in MCF-7 cells and
      markedly increased in size and number at 24 hours following 17beta-estradiol and,
      in particular diarylpropionitrile, treatment. These speckles were coexpressed
      with ERbeta1 and ERbeta2. Presence of S105-ERbeta in breast cancer and
      association with improved survival, even in endocrine resistant breast tumors
      suggest S105-ERbeta might be a useful additional prognostic marker in this
      disease.

PMID- 20696773
TI  - Protein kinase CK1alphaLS promotes vascular cell proliferation and intimal
      hyperplasia.
AB  - Protein kinase CK1alpha regulates several fundamental cellular processes
      including proliferation and differentiation. Up to four forms of this kinase are
      expressed in vertebrates resulting from alternative splicing of exons; these
      exons encode either the L-insert located within the catalytic domain or the S
      insert located at the C terminus of the protein. Whereas the L-insert is known to
      target the kinase to the nucleus, the functional significance of nuclear
      CK1alphaLS has been unclear. Here we demonstrate that selective L-insert-targeted
      short hairpin small interfering RNA-mediated knockdown of CK1alphaLS in human
      vascular endothelial cells and vascular smooth muscle cells impairs proliferation
      and abolishes hydrogen peroxide-stimulated proliferation of vascular smooth
      muscle cells, with the cells accumulating in G(0)/G(1). In addition, selective
      knockdown of CK1alphaLS in cultured human arteries inhibits vascular activation,
      preventing smooth muscle cell proliferation, intimal hyperplasia, and
      proteoglycan deposition. Knockdown of CK1alphaLS results in the harmonious down
      regulation of its target substrate heterogeneous nuclear ribonucleoprotein C and
      results in the altered expression or alternative splicing of key genes involved
      in cellular activation including CXCR4, MMP3, CSF2, and SMURF1. Our results
      indicate that the nuclear form of CK1alpha in humans, CK1alphaLS, plays a
      critical role in vascular cell proliferation, cellular activation, and hydrogen
      peroxide-mediated mitogenic signal transduction.

PMID- 20696774
TI  - Early oligodendrocyte/myelin pathology in Alzheimer's disease mice constitutes a
      novel therapeutic target.
AB  - The detection of myelin disruptions in Alzheimer's disease (AD)-affected brain
      raises the possibility that oligodendrocytes undergo pathophysiological assault
      over the protracted course of this neurodegenerative disease. Oligodendrocyte
      compromise arising from direct toxic effects imparted by pathological amyloid
      beta peptides and/or through signals derived from degenerating neurons could play
      an important role in the disease process. We previously demonstrated that 3xTg-AD
      mice, which harbor the human amyloid precursor protein Swedish mutant transgene,
      presenilin knock-in mutation, and tau P301L mutant transgene, exhibit significant
      alterations in overall myelination patterns and oligodendrocyte status at time
      points preceding the appearance of amyloid and tau pathology. Herein, we
      demonstrate that Abeta(1-42) leads to increased caspase-3 expression and
      apoptotic cell death of both nondifferentiated and differentiated mouse
      oligodendrocyte precursor (mOP) cells in vitro. Through use of a recombinant
      adeno-associated virus serotype-2 (rAAV2) vector expressing an Abeta(1-42)
      specific intracellular antibody (intrabody), oligodendrocyte and myelin marker
      expression, as well as myelin integrity, were restored in the vector-infused
      brain regions of 3xTg-AD mice. Overall, this work provides further insights into
      the impact of Abeta(1-42)-mediated toxicity on the temporal and spatial
      progression of subtle myelin disruption during the early presymptomatic stages of
      AD and may help to validate new therapeutic options designed to avert these early
      impairments.

PMID- 20696775
TI  - Interleukin-1 as a phenotypic immunomodulator in keratinizing squamous metaplasia
      of the ocular surface in Sjogren's syndrome.
AB  - Chronic inflammation of the ocular surface in Sjogren's syndrome (SS) is
      associated with a vision-threatening, phenotypic change of the ocular surface,
      which converts from a nonkeratinized, stratified squamous epithelium to a
      nonsecretory, keratinized epithelium. This pathological process is known as
      squamous metaplasia. Based on a significant correlation between ocular surface
      interleukin (IL)-1beta expression and squamous metaplasia in patients with SS, we
      investigated the role of IL-1 in the pathogenesis of squamous metaplasia in an
      animal model that mimics the clinical characteristics of SS. Using autoimmune
      regulator (aire)-deficient mice, we assessed lacrimal gland and ocular surface
      immunopathology by quantifying the infiltration of major histocompatibility
      complex class II(+) (I-A(d+)) dendritic cells and CD4(+) T cells. We examined
      squamous metaplasia using a biomarker of keratinization, small proline-rich
      protein 1B. We used lissamine green staining as a readout for ocular surface
      epitheliopathy and Alcian blue/periodic acid-Schiff histochemical analysis to
      characterize goblet cell muco-glycoconjugates. Within 8 weeks, the eyes of aire
      deficient mice were pathologically keratinized with significant epithelial damage
      and altered mucin glycosylation. Although knockdown of IL-1 receptor 1 did not
      attenuate lymphocytic infiltration of the lacrimal gland or eye, it significantly
      reduced ocular surface keratinization, epitheliopathy, and muco-glycoconjugate
      acidification. These data demonstrate a phenotypic modulation role for IL-1 in
      the pathogenesis of squamous metaplasia and suggest that IL-1 receptor 1-targeted
      therapies may be beneficial for treating ocular surface disease associated with
      SS.

PMID- 20696776
TI  - CD34 is required for infiltration of eosinophils into the colon and pathology
      associated with DSS-induced ulcerative colitis.
AB  - Eosinophil migration into the gut and the release of granular mediators plays a
      critical role in the pathogenesis of inflammatory bowel diseases, including
      ulcerative colitis. We recently demonstrated that eosinophil migration into the
      lung requires cell surface expression of the sialomucin CD34 on mast cells and
      eosinophils in an asthma model. Based on these findings, we investigated a
      similar role for CD34 in the migration of eosinophils and other inflammatory
      cells into the colon as well as explored the effects of CD34 ablation on disease
      development in a dextran sulfate sodium-induced model of ulcerative colitis. Our
      findings demonstrate decreased disease severity in dextran sulfate sodium-treated
      Cd34(-/-) mice, as assessed by weight loss, diarrhea, bleeding, colon shortening
      and tissue pathology, compared with wild-type controls. CD34 was predominantly
      expressed on eosinophils within inflamed colon tissues, and Cd34(-/-) animals
      exhibited drastically reduced colon eosinophil infiltration. Using chimeric
      animals, we demonstrated that decreased disease pathology resulted from loss of
      CD34 from bone marrow-derived cells and that eosinophilia in Cd34(-/-)IL5(Tg)
      animals was sufficient to overcome protection from disease. In addition, we
      demonstrated a decrease in peripheral blood eosinophil numbers following dextran
      sulfate sodium treatment. These findings demonstrate that CD34 was expressed on
      colon-infiltrating eosinophils and played a role in eosinophil migration.
      Further, our findings suggest CD34 is required for efficient eosinophil
      migration, but not proliferation or expansion, in the development of ulcerative
      colitis.

PMID- 20696777
TI  - Heterogeneous and complex rearrangements of chromosome arm 6q in chondromyxoid
      fibroma: delineation of breakpoints and analysis of candidate target genes.
AB  - Chondromyxoid fibroma (CMF) is an uncommon benign cartilaginous tumor of bone
      usually occurring during the second decade of life. CMF is associated with
      recurrent rearrangements of chromosome bands 6p23-25, 6q12-15, and 6q23-27. To
      delineate further the role and frequency of the involvement of three candidate
      regions (6q13, 6q23.3 and 6q24) in the pathogenesis of CMF, we studied a group of
      43 cases using a molecular cytogenetic approach. Fluorescence in situ
      hybridization with probe sets bracketing the putative breakpoint regions was
      performed in 30 cases. The expression level of nearby candidate genes was studied
      by immunohistochemistry and quantitative RT-PCR in 24 and 23 cases, respectively.
      Whole-genome copy number screening was performed by array comparative genomic
      hybridization in 16 cases. Balanced and unbalanced rearrangements of 6q13 and
      6q23.3 occurred in six and five cases, respectively, and a hemizygous deletion in
      6q24 was found in five cases. Two known tumor suppressor genes map to the latter
      region: PLAGL1 and UTRN. However, neither of these two genes nor BCLAF1 and
      COL12A1, respectively located in 6q23.3 and 6q13, showed altered expression.
      Therefore, although rearrangements of chromosomal regions 6q13, 6q23.3, and 6q24
      are common in CMF, the complexity of the changes precludes the use of a single
      fluorescence in situ hybridization probe set as an adjunct diagnostic tool. These
      data indicate that the genetic alterations in CMF are heterogeneous and are
      likely a result of a cryptic rearrangement beyond the resolution level of
      combined binary ratio fluorescence in situ hybridization or a point mutation.

PMID- 20696778
TI  - Statin attenuates experimental anti-glomerular basement membrane
      glomerulonephritis together with the augmentation of alternatively activated
      macrophages.
AB  - Macrophages are heterogeneous and include classically activated M1 and
      alternatively activated M2 macrophages, characterized by pro- and anti
      inflammatory functions, respectively. Macrophages that express heme oxygenase-1
      also exhibit anti-inflammatory effects. We assessed the anti-inflammatory effects
      of statin in experimental anti-glomerular basement membrane glomerulonephritis
      and in vitro, focusing on the macrophage heterogeneity. Rats were induced anti
      glomerular basement membrane glomerulonephritis and treated with atorvastatin (20
      mg/kg/day) or vehicle (control). Control rats showed infiltration of macrophages
      in the glomeruli at day 3 and developed crescentic glomerulonephritis by day 7,
      together with increased mRNA levels of the M1 macrophage-associated cytokines,
      interferon-gamma, tumor necrosis factor-alpha, and interleukin-12. In contrast,
      statin reduced the level of proteinuria, reduced infiltration of macrophages in
      glomeruli with suppression of monocyte chemotactic protein-1 expression, and
      inhibited the formation of necrotizing and crescentic lesions. The number of
      glomerular ED3-positive macrophages decreased with down-regulation of M1
      macrophage-associated cytokines. Furthermore, statin augmented ED2-positive M2
      macrophages with up-regulation of the M2 macrophage-associated chemokines and
      cytokines, chemokine (C-C motif) Iigand-17 and interleukin-10. Statin also
      increased the glomerular interleukin-10-expressing heme oxygenase-1-positive
      macrophages. Statin inhibited macrophage development, and suppressed ED3-positive
      macrophages, but augmented ED2-positive macrophages in M2-associated cytokine
      environment in vitro. We conclude that the anti-inflammatory effects of statin in
      glomerulonephritis are mediated through inhibition of macrophage infiltration as
      well as augmentation of anti-inflammatory macrophages.

PMID- 20696779
TI  - Delayed cardiomyopathy in dystrophin deficient mdx mice relies on intrinsic
      glutathione resource.
AB  - Oxidative stress contributes to the pathogenesis of Duchenne muscular dystrophy
      (DMD). Although they have been a model for DMD, mdx mice exhibit slowly
      developing cardiomyopathy. We hypothesized that disease process was delayed owing
      to the development of an adaptive mechanism against oxidative stress, involving
      glutathione synthesis. At 15 to 20 weeks of age, mdx mice displayed a 33%
      increase in blood glutathione levels compared with age-matched C57BL/6 mice. In
      contrast, cardiac glutathione content was similar in mdx and C57BL/6 mice as a
      result of the balanced increased expression of glutamate cysteine ligase
      catalytic and regulatory subunits ensuring glutathione synthesis in the mdx mouse
      heart, as well as increased glutathione peroxidase-1 using glutathione. Oral
      administration from 10 weeks of age of the glutamate cysteine ligase inhibitor, l
      buthionine(S,R)-sulfoximine (BSO, 5 mmol/L), led to a 33% and 50% drop in blood
      and cardiac glutathione, respectively, in 15- to 20-week-old mdx mice. Moreover,
      20-week-old BSO-treated mdx mice displayed left ventricular hypertrophy
      associated with diastolic dysfunction, discontinuities in beta-dystroglycan
      expression, micronecrosis and microangiopathic injuries. Examination of the
      glutathione status in four DMD patients showed that three displayed systemic
      glutathione deficiency as well. In conclusion, low glutathione resource hastens
      the onset of cardiomyopathy linked to a defect in dystrophin in mdx mice. This is
      relevant to the glutathione deficiency that DMD patients may suffer.

PMID- 20696780
TI  - Characterization of the KRN cell transfer model of rheumatoid arthritis (KRN
      CTM), a chronic yet synchronized version of the K/BxN mouse.
AB  - In this study, a chronic yet synchronized version of the K/BxN mouse, the KRN
      cell transfer model (KRN-CTM), was developed and extensively characterized. The
      transfer of purified splenic KRN T cells into T cell-deficient B6.TCR.Calpha(-/
      )H-2(b/g7) mice induced anti-glucose 6-phosphate isomerase antibody-dependent
      chronic arthritis in 100% of the mice with uniform onset of disease 7 days after
      T cell transfer. Cellular infiltrations were assessed by whole-ankle transcript
      microarray, cytokine and chemokine levels, and microscopic and
      immunohistochemical analyses 7 through 42 days after T cell transfer. Transcripts
      identified an influx of monocytes/macrophages and neutrophils into the ankles and
      identified temporal progression of cartilage damage and bone resorption. In both
      serum and ankle tissue there was a significant elevation in interleukin-6,
      whereas macrophage inflammatory protein-1 alpha and monocyte chemotactic protein
      1 were only elevated in tissue. Microscopic and immunohistochemical analyses
      revealed a time course for edema, synovial hypertrophy and hyperplasia,
      infiltration of F4/80-positive monocytes/macrophages and myeloperoxidase-positive
      neutrophils, destruction of articular cartilage, pannus invasion, bone
      resorption, extra-articular fibroplasia, and joint ankylosis. The KRN cell
      transfer model replicates many features of chronic rheumatoid arthritis in humans
      in a synchronized manner and lends itself to manipulation of adoptively
      transferred T cells and characterizing specific genes and T cell subsets
      responsible for rheumatoid arthritis pathogenesis and progression.

PMID- 20696781
TI  - Modulation of N-type calcium currents by presynaptic imidazoline receptor
      activation in rat superior cervical ganglion neurons.
AB  - Presynaptic imidazoline receptors (R(i-pre)) are found in the sympathetic axon
      terminals of animal and human cardiovascular systems, and they regulate blood
      pressure by modulating the release of peripheral noradrenaline (NA). The cellular
      mechanism of R(i-pre)-induced inhibition of NA release is unknown. We, therefore,
      investigated the effect of R(i-pre) activation on voltage-dependent Ca(2+)
      channels in rat superior cervical ganglion (SCG) neurons, using the conventional
      whole-cell patch-clamp method. Cirazoline (30 MUM), an R(i-pre) agonist as well
      as an alpha-adrenoceptor (R(alpha)) agonist, decreased Ca(2+) currents (I(Ca)) by
      about 50% in a voltage-dependent manner with prepulse facilitation. In the
      presence of low-dose rauwolscine (3 MUM), which blocks the alpha(2)-adrenoceptor
      (R(alpha2)), cirazoline still inhibited I(Ca) by about 30%, but prepulse
      facilitation was significantly attenuated. This inhibitory action of cirazoline
      was almost completely prevented by high-dose rauwolscine (30 MUM), which blocks
      R(i-pre) as well as R(alpha2). In addition, pretreatment with LY320135 (10 MUM),
      another R(i-pre) antagonist, in combination with low-dose rauwolscine (3 MUM),
      also blocked the R(alpha2)-resistant effect of cirazoline. Addition of guanosine
      5-O-(2-thiodiphosphate) (2 mm) to the internal solutions significantly attenuated
      the action of cirazoline. However, pertussis toxin (500 ng ml(1)) did not
      significantly influence the inhibitory effect of cirazoline. Moreover, cirazoline
      (30 MUM) suppressed M current in SCG neurons cultured overnight. Finally, omega
      conotoxin (omega-CgTx) GVIA (1 MUM) obstructed cirazoline-induced current
      inhibition, and cirazoline (30 MUM) significantly decreased the frequency of
      action potential firing in a partly reversible manner. This cirazoline-induced
      inhibition of action potential firing was almost completely occluded in the
      presence of omega-CgTx. Taken together, our results suggest that activation of
      R(i-pre) in SCG neurons reduced N-type I(Ca) in a pertussis toxin- and voltage
      insensitive pathway, and this inhibition attenuated repetitive action potential
      firing in SCG neurons.

PMID- 20696782
TI  - Acute vascular endothelial growth factor expression during hypertrophy is muscle
      phenotype specific and localizes as a striated pattern within fibres.
AB  - Skeletal muscle hypertrophy requires the co-ordinated expression of locally
      acting growth factors that promote myofibre growth and concurrent adaptive
      changes in the microvasculature. These studies tested the hypothesis that
      vascular endothelial growth factor (VEGF) and heparin-binding epidermal growth
      factor (HB-EGF) expression are upregulated during the early stages of
      compensatory muscle growth induced by chronic functional overload (FO). Bilateral
      FO of the plantaris and soleus muscles was induced for 3 or 7 days in the
      hindlimbs of adult female Sprague-Dawley rats (n = 5 per group) and compared with
      control (non-FO) rats. Relative muscle mass (in mg (kg body weight)(-1))
      increased by 18 and 24% after 3 days and by 20 and 33% after 7 days in the
      plantaris and soleus muscles, respectively. No differences in HB-EGF mRNA or
      protein were observed in either muscle of FO rats relative to control muscles.
      The VEGF mRNA was similar in the soleus muscles of FO and control rats, whereas a
      significant elevation occurred at 3 and 7 days of FO in the plantaris muscle.
      However, VEGF protein expression after 3 days of FO exhibited a differential
      response; expression in the soleus muscle decreased 1.6-fold, whereas that in the
      plantaris muscle increased 1.8-fold compared with the control muscle. After 7
      days of FO, VEGF protein remained elevated within the plantaris muscle, but
      returned to basal levels in the soleus. Robust basal HB-EGF and VEGF protein
      expression was consistently seen in control muscles. In all groups,
      immunohistochemistry for VEGF protein displayed a distinct striated expression
      pattern within myofibres, with considerably less labelling in extracellular
      spaces. Constitutive expression of HB-EGF and VEGF in control myofibres is
      consistent with housekeeping roles for these growth factors in skeletal muscle
      tissue. However, the specific patterns of VEGF expression in these muscles during
      FO may reflect the chronic changes in neural recruitment between muscles and the
      co-ordination of angiogenic and/or other hypertrophic responses.

PMID- 20696783
TI  - Acute physical activity effects on cardiac gene expression.
AB  - Regular bouts of physical activity may cause changes in gene expression that
      accumulate over time and ultimately affect phenotypes, such as body weight, blood
      lipid profile and tumour development. Furthermore, acute activity may affect gene
      expression and phenotypes differently depending on whether the individual is
      regularly inactive or active. One-month-old male Sprague-Dawley rats (n = 72)
      were equally divided into SED (standard laboratory cage, n = 24), PA (large
      activity box, n = 24) and EX groups (exercise wheel inside standard cage, n =
      24). At 3 months of age, half the animals from each group were killed at rest and
      the other half following 30 min of physical activity. The RNA was extracted from
      cardiac tissue, and microarray analysis was performed on 27,000 genes. Select
      gene results were validated using quantitative PCR. No gene expression
      differences occurred when comparing all 3-month-old groups at rest. A relatively
      small percentage of genes (1.9%) were differentially expressed (P < 0.05)
      following acute swimming activity in all groups, but only 37 unique and
      identifiable genes reached or exceeded twofold differences in expression. The
      genes Atf3, Fos, Apold1 and Pxdn were expressed differently among SED, PA and EX
      following acute activity, with a clear separation of the magnitude in gene
      expression with SED > PA > EX. Differences in gene expression levels in young
      physically inactive and active animals following acute activity have different
      regulatory roles in gene networks that affect health-related phenotypes.

PMID- 20696784
TI  - WISE-2005: prolongation of left ventricular pre-ejection period with 56 days head
      down bed rest in women.
AB  - This study tested the hypothesis that prolonged physical deconditioning affects
      the coupling of left ventricular depolarization to its ejection (the pre-ejection
      period, PEPi) and that this effect is minimized by exercise countermeasures.
      Following assignment to non-exercise (Control) and exercise groups (Exercise), 14
      females performed 56 days of continuous head-down tilt bed rest. Measurements of
      the electrocardiogram (ECG) and stroke volume (Doppler ultrasound) during supine
      rest were obtained at baseline prior to (Pre) and after (Post) the head-down tilt
      bed rest (HDBR) period. Compared with Pre, the PEPi was increased following head
      down tilt bed rest (main effect, P < 0.005). This effect was most dominant in the
      Control group [Pre = 0.038 +/- 0.06 s (s.d.) versus Post = 0.054 +/- 0.011 s; P <
      0.001]. In the Exercise group, PEPi was 0.032 +/- 0.005 s Pre and 0.038 +/- 0.018
      s Post; P= 0.08. Neither the QRS interval nor cardiac afterload was modified by
      head-down tilt bed rest in Control or Exercise groups. Low-dose isoprenaline
      infusion reversed the head-down tilt bed rest-induced delay in the PEPi. These
      results suggest that head-down tilt bed rest leads to a delayed onset of systolic
      ejection following left ventricular depolarization in a manner that is affected
      little by the exercise countermeasure but is related to beta-adrenergic pathways.
      The delayed onset of systole following head-down tilt bed rest appears to be
      related to mechanism(s) affecting contraction of the left ventricle rather than
      its depolarization.

PMID- 20696785
TI  - Seeing is believing! Imaging Ca2+-signalling events in living cells.
AB  - Ever since it was shown that maintenance of muscle contraction required the
      presence of extracellular Ca(2+), evidence has accumulated that Ca(2+) plays a
      crucial role in excitation-contraction coupling. This culminated in the use of
      the photoprotein aequorin to demonstrate that [Ca(2+)](i) increased after
      depolarization but before contraction in barnacle muscle. Green fluorescent
      protein was extracted from the same jellyfish as aequorin, so this work also has
      important historical links to the use of fluorescent proteins as markers in
      living cells. The subsequent development of cell-permeant Ca(2+) indicators
      resulted in a dramatic increase in related research, revealing Ca(2+) to be a
      ubiquitous cell signal. High-speed, confocal Ca(2+) imaging has now revealed
      subcellular detail not previously apparent, with the identification of Ca(2+)
      sparks. These act as building blocks for larger transients during excitation
      contraction coupling in cardiac muscle, but their function in smooth muscle
      appears more diverse, with evidence suggesting both 'excitatory' and 'inhibitory'
      roles. Sparks can activate Ca(2+)-sensitive Cl() and K(+) currents, which exert
      positive and negative feedback, respectively, on global Ca(2+) signalling,
      through changes in membrane potential and activation of voltage-operated Ca(2+)
      channels. Calcium imaging has also demonstrated that agonists that appear to
      evoke relatively tonic increases in average [Ca(2+)](i) at the whole tissue level
      often stimulate much higher frequency phasic Ca(2+) oscillations at the cellular
      level. These findings may require re-evaluation of some of our models of Ca(2+)
      signalling to account for newly revealed cellular and subcellular detail. Future
      research in the field is likely to make increasing use of genetically coded
      Ca(2+) indicators expressed in an organelle- or tissue-specific manner.

PMID- 20696786
TI  - Sex differences in the effects of physical training on sweat gland responses
      during a graded exercise.
AB  - We assessed sex differences in the sweat gland response to changes in exercise
      intensity with respect to subjects' physical training status. In total, 37
      subjects participated (10 trained and 10 untrained females, and 8 trained and 9
      untrained males). Each subject cycled continuously at 35, 50 and 65% of their
      maximal O(2) uptake (V(O2max)) for 60 min at an ambient temperature of 30 degrees
      C and a relative humidity of 45%. The mean local sweating rate (SR) on the
      forehead, chest, back, forearm and thigh was significantly greater in the trained
      subjects than in the untrained subjects of both sexes. The degree of the increase
      in SR with physical training was greater in males than in females at higher
      levels of exercise intensity. This increase in SR depended primarily on an
      increase in the sweat output per gland (SGO) in both sexes. However, control of
      the SR increase with increasing exercise intensity was altered by training in
      females, i.e. the increase in SR from exercise at 50 to 65% V(O2max) depended
      only on an increase in SGO in trained females and males and untrained males, but
      it depended on increases in activated sweat glands and the SGO in untrained
      females. It was concluded that training improved the sweating response, and a sex
      difference was observed in the degree of improvement in the sweating response due
      to physical training. This sex difference became more pronounced with increasing
      exercise intensity. A sex difference was observed in the control of sweating rate
      to an increase in exercise intensity, i.e. the maximal activated sweat gland
      responses of untrained females required a higher body temperature or work
      intensity than the other groups.

PMID- 20696787
TI  - The relevance of central command for the neural cardiovascular control of
      exercise.
AB  - This paper briefly reviews the role of central command in the neural control of
      the circulation during exercise. While defined as a feedforward component of the
      cardiovascular control system, central command is also associated with perception
      of effort or effort sense. The specific factors influencing perception of effort
      and their effect on autonomic regulation of cardiovascular function during
      exercise can vary according to condition. Centrally mediated integration of
      multiple signals occurring during exercise certainly involves feedback
      mechanisms, but it is unclear whether or how these signals modify central command
      via their influence on perception of effort. As our understanding of central
      neural control systems continues to develop, it will be important to examine more
      closely how multiple sensory signals are prioritized and processed centrally to
      modulate cardiovascular responses during exercise. The purpose of this article is
      briefly to review the concepts underlying central command and its assessment via
      perception of effort, and to identify potential areas for future studies towards
      determining the role and relevance of central command for neural control of
      exercise.

PMID- 20696788
TI  - Defining a longitudinal survival model to examine forced treadmill running as a
      countermeasure for diet-induced weight gain.
AB  - Diet-induced weight gain increases disease risk via disruption of the innate
      immune system. Flow cytometry is commonly used to assess the immune system;
      however, in mice such measurements traditionally require terminal procedures and
      tissue collection to generate sufficient sample. The present study refined an
      existing flow cytometry method to reduce the number of mice needed to
      longitudinally measure monocytes. CD-1 male mice were randomly assigned to one of
      the three groups: DS (diet-induced weight gain + sedentary), DE (diet-induced
      weight gain + forced treadmill running [total distance 35,755 +/- 1832 m]) or NS
      (normal weight gain + sedentary). DS and DE consumed a 60% fat diet and NS
      consumed a 10% fat diet ad libitum. Saphenous vein blood samples were collected
      weekly for a period of six weeks and three-colour flow cytometry was used to
      measure changes in monocyte (CD11b(+)/14(+)) concentration and cell-surface toll
      like receptor 4 (TLR4) expression. DS (18%) and DE (17%) gained more weight than
      NS (P < 0.001). On a group basis, DS expressed 17% more TLR4 than DE and NS (P =
      0.005). The present study demonstrates that a longitudinal survival model can be
      used to reduce the number of animals needed to complete flow cytometry
      experiments. Exercise during diet-induced weight prevented some (decreased
      monocyte TLR4 expression) but not all aspects of innate immune system function.

PMID- 20696789
TI  - Surgical anatomy of the swine face.
AB  - In order to develop tissue engineering applications for oral and maxillofacial
      surgery, the surgical anatomy of the miniature pig's face was investigated in
      three miniature pig cadavers and three anaesthetized miniature pigs using
      identical procedures that were previously described for humans. A preauricular
      incision with a retromandibular and a submandibular extension was initially made
      through the facial skin and subcutaneous tissues. The underlying tissues were
      then carefully dissected in order to progressively expose the platysma muscle,
      the superficial layer of deep cervical fascia, the marginal mandibular branch and
      buccal branch of the facial nerve, the mental nerve and the mandibular skeleton.
      The marginal mandibular branch of the facial nerve has an upper and lower
      division. Stimulation of the facial nerve and its branches showed that the upper
      division of the marginal mandibular branch innervates muscles and tissues in the
      upper lip and nose region, and the lower division innervates muscles and tissues
      in the lower lip region. The gross anatomy of the maxillofacial region in the
      pigs was found to be similar to that of humans. Although the distributions of the
      marginal mandibular branch of the facial nerve and the mental nerve are different
      from that of humans, we concluded that miniature pigs are a suitable experimental
      model for the preclinical development of tissue engineering applications in oral
      and maxillofacial surgery.

PMID- 20696790
TI  - Sublingual and submandibular blood collection in mice: a comparison of effects on
      body weight, food consumption and tissue damage.
AB  - In a large number of animal experiments, blood collection is crucial for
      achieving the study aim. Requirements on sampling techniques used include their
      practicability, their effectiveness in terms of obtaining the desired blood
      volume, sample quality and low impact on animal's wellbeing. Numerous methods for
      blood collection from mice have been published. For large blood volumes,
      submandibular and sublingual bleeding was developed as alternatives to the
      retrobulbar bleeding method, which is considered controversial as it results in
      severe tissue damage. Only a few studies report the use of submandibular and
      sublingual techniques in mice. In particular, the degree of tissue damage or
      influence on animal's wellbeing due to submandibular bleeding in conscious mice
      has not yet been clearly assessed. This gap in the knowledge base has been filled
      by our exploratory study that revealed clear differences between both techniques.
      Defence movements during submandibular blood collection in conscious mice
      resulted in more complications and revealed insufficient blood sample quality due
      to the prolonged duration of blood collection. In addition, it is likely that
      these movements may have caused lesions to be more pronounced. Changes in red
      blood cell parameters (red blood cell count, haemoglobin and haematocrit), in
      glucose and in total protein concentrations observed in anaesthetized animals
      were most likely related to anaesthesia. Sublingually punctured mice gained
      significantly more body weight than submandibularly punctured mice, likely due to
      less severe tissue lesions and improved healing processes. Based on these
      results, we recommend the sublingual blood collection technique to be used in
      mice. However, if the submandibular bleeding technique is used, it should be
      performed in anaesthetized mice only.

PMID- 20696791
TI  - Extreme positive selection on a new highly-expressed larval glycoprotein (LGP)
      gene in Galaxias fishes (Osmeriformes: Galaxiidae).
AB  - We describe the intron-exon structure and DNA/protein sequences of a new larval
      glycoprotein (LGP) gene from nine species of galaxiid fish. The gene has a
      distant similarity to Danio THP (Tamm-Horsfall urinary glycoprotein; uromodulin)
      and cichlid SPP120 (seminal plasma glycoprotein) due to conserved features of its
      zona pellucida (ZP) domain, including eight highly conserved cysteines and a
      consensus furin cleavage site. Using a combination of 454 sequencing of cDNA and
      exon-primed intron-spanning sequencing of genomic DNA, we obtained full sequences
      of the coding region (996 bp) and its intervening sequences (1,459 bp). LGP shows
      an exceptionally strong signal of positive selection over the entire coding
      region, as evidenced by d(N)/d(S) values >1. Across nine species of Galaxias,
      87/332 (26%) amino acid residues are variable, compared with 9/386 (2%) for
      mitochondrial cytochrome b (cytb) in the same group of species. Across 36
      interspecific pairwise comparisons, genetic distances are in all cases larger for
      coding region than for introns, by a factor of 2.4-fold on average. Reading
      frame, gene structure, splice sites, and many ZP motifs are conserved across all
      species. Together with the fact that the gene is expressed in all species, these
      results argue clearly against the possibility of a pseudogene. We show by 454
      sequencing and quantitative polymerase chain reaction that the transcript is
      abundant (ca. 0.5%) in newly hatched larvae and appears to be almost absent from
      a range of adult tissues. We postulate that the strong Darwinian evolution
      exhibited by this protein may reflect some type of immunoprotection at this
      vulnerable larval stage.

PMID- 20696792
TI  - Changes in coagulation indexes and occurrence of venous thromboembolism in
      patients with Cushing's syndrome: results from a prospective study before and
      after surgery.
AB  - OBJECTIVES: To evaluate whether patients with Cushing's syndrome (CS) had i)
      changes in coagulative and fibrinolytic parameters associated with CS activity
      and ii) higher prevalence of venous thromboembolic events (VTE). DESIGN:
      Prospective study conducted on patients with CS evaluated at diagnosis and 12
      months after surgery. PATIENTS AND METHODS: Forty patients with active CS (36
      with Cushing's disease (CD) and 4 with an adrenal adenoma) were evaluated. Forty
      normal subjects and 70 patients with non-ACTH-secreting pituitary adenomas served
      as controls. All patients and controls underwent an assessment of coagulation and
      fibrinolysis indexes before and after surgery. RESULTS: CS patients at baseline
      had a hypercoagulative phenotype when compared with normal subjects (activated
      partial thromboplastin time (aPTT), fibrinogen, D-Dimer, von Willebrand factor
      (VWF), plasminogen activator inhibitor 1 (PAI-1 or SERPINE1), antithrombin III
      (ATIII or SERPINC1), P<0.0001, alpha(2) antiplasmin, P=0.0004, thrombin
      antithrombin complex (TAT), P=0.01, factor IX (F9), P=0.03). Patients with still
      active disease after surgery had higher coagulative parameters than those in
      remission (VWF (P<0.0001), PAI-1 (P=0.004), TAT (P=0.0001), ATIII (P=0.0002) and
      alpha(2) antiplasmin (or SERPINF2; P=0.006)), whereas aPTT levels (P=0.007) were
      significantly reduced. VTE occurred in three patients with CD (7.5%): one had a
      pulmonary embolism and two patients had a deep venous thrombosis; no patients
      submitted to transsphenoidal surgery for non-Cushing's pituitary adenoma had VTE
      (P=0.04). CONCLUSIONS: Patients with CS have a procoagulative phenotype due to
      cortisol-associated changes in haemostatic and fibrinolytic markers, leading to
      increased incidence of VTE. Thromboprophylaxis seems to be appropriated in
      patients with active disease, particularly in the postoperative period.

PMID- 20696793
TI  - Filial piety by contract? The emergence, implementation, and implications of the
      "family support agreement" in China.
AB  - China has the largest aging population in the world today. Despite the Chinese
      tradition of filial piety, economic, social, cultural, and familial changes have
      made it increasingly difficult for older Chinese to receive support from adult
      children. To ensure parental support, the Family Support Agreement (FSA) emerged
      from a local community in the mid-1980s. Since then, the FSA has been promoted
      and monitored by the government. By the end of 2005, FSAs had been signed by more
      than 13 million rural families across China and is now finding its way into
      cities. A voluntary contract between older parents and adult children concerning
      parental provisions, the FSA represents an innovation to help meet the challenge
      of providing elder support. Although the FSA's moral persuasion is based on
      filial piety, violations of the FSA are subject to penalties by law. As the first
      systematic and comprehensive exploratory study on the FSA, this article examines
      (a) the FSA's emergence, content, legal foundation, and implementation; (b) the
      role of the government and the legal system in promoting or monitoring FSAs; (c)
      the FSA's strengths, limitations, and challenges; (d) the FSA's implications in
      light of Chinese history, intergenerational contract, filial piety, and
      intergenerational relations; and (e) the future of the FSA as a social policy.

PMID- 20696794
TI  - Poly(ADP-ribose) polymerase 1 modulates the lethality of CHK1 inhibitors in
      carcinoma cells.
AB  - Prior studies have demonstrated that inhibition of CHK1 can promote the
      activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and
      phosphorylation of histone H2AX and that inhibition of poly(ADP-ribose)
      polymerase 1 (PARP1) can affect growth factor-induced ERK1/2 activation. The
      present studies were initiated to determine whether CHK1 inhibitors interacted
      with PARP1 inhibition to facilitate apoptosis. Transient expression of dominant
      negative CHK1 raised basal ERK1/2 activity and prevented CHK1 inhibitors from
      activating ERK1/2. CHK1 inhibitors modestly increased the levels of PARP1 ADP
      ribosylation and molecular or small-molecule inhibition of PARP1 blocked CHK1
      inhibitor-stimulated histone H2AX phosphorylation and activation of ERK1/2.
      Stimulated histone H2AX phosphorylation was ataxia telangiectasia-mutated protein
      dependent. Multiple CHK1 inhibitors interacted in a greater than additive fashion
      with multiple PARP1 inhibitors to cause transformed cell-killing in short-term
      viability assays and synergistically killed tumor cells in colony-formation
      assays. Overexpression of BCL-xL or loss of BAX/BAK function, but not the
      function of BID, suppressed CHK1 inhibitor + PARP1 inhibitor lethality.
      Inhibition of BCL-2 family protein function enhanced CHK1 inhibitor + PARP1
      inhibitor lethality and restored drug-induced cell-killing in cells
      overexpressing BCL-xL. Thus, PARP1 plays an important role in regulating the
      ability of CHK1 inhibitors to activate ERK1/2 and the DNA damage response. An
      inability of PARP1 to modulate this response results in transformed cell death
      mediated through the intrinsic apoptosis pathway.

PMID- 20696797
TI  - The cluster-randomized Quality Initiative in Rectal Cancer trial: evaluating a
      quality-improvement strategy in surgery.
AB  - BACKGROUND: Following surgery for rectal cancer, two unfortunate outcomes for
      patients are permanent colostomy and local recurrence of cancer. We tested
      whether a quality-improvement strategy to change surgical practice would improve
      these outcomes. METHODS: Sixteen hospitals were cluster-randomized to the
      intervention (Quality Initiative in Rectal Cancer strategy) or control (normal
      practice) arm. Consecutive patients with primary rectal cancer were accrued from
      May 2002 to December 2004. Surgeons at hospitals in the intervention arm could
      voluntarily participate by attending workshops, using opinion leaders, inviting a
      study team surgeon to demonstrate optimal techniques of total mesorectal
      excision, completing postoperative questionnaires, and receiving audits and
      feedback. Main outcome measures were hospital rates of permanent colostomy and
      local recurrence of cancer. RESULTS: A total of 56 surgeons (n = 558 patients)
      participated in the intervention arm and 49 surgeons (n = 457 patients) in the
      control arm. The median follow-up of patients was 3.6 years. In the intervention
      arm, 70% of surgeons participated in workshops, 70% in intraoperative
      demonstrations and 71% in postoperative questionnaires. Surgeons who had an
      intraoperative demonstration provided care to 86% of the patients in the
      intervention arm. The rates of permanent colostomy were 39% in the intervention
      arm and 41% in the control arm (odds ratio [OR] 0.97, 95% confidence interval
      [CI] 0.63-1.48). The rates of local recurrence were 7% in the intervention arm
      and 6% in the control arm (OR 1.06, 95% CI 0.68-1.64). INTERPRETATION: Despite
      good participation by surgeons, the resource-intense quality-improvement strategy
      did not reduce hospital rates of permanent colostomy or local recurrence compared
      with usual practice.

PMID- 20696798
TI  - Uremic frost.

PMID- 20696799
TI  - Neuroleptic malignant syndrome: a neuroimmunologic hypothesis.

PMID- 20696800
TI  - Age-related macular degeneration.

PMID- 20696801
TI  - Gulf oil spill exposes gaps in public health knowledge.

PMID- 20696802
TI  - Voluntary sodium reductions far from "uncharted".

PMID- 20696803
TI  - Beautifying hospitals: a tough sell.

PMID- 20696804
TI  - Report calls for overhaul of US food safety system.

PMID- 20696808
TI  - End of life.

PMID- 20696809
TI  - The right to give blood.

PMID- 20696810
TI  - The right to give blood.

PMID- 20696811
TI  - Harassment from misguided mayoral candidate.

PMID- 20696812
TI  - Hear some evil, see some evil, report no evil.

PMID- 20696813
TI  - Why can't I get my veins unblocked in Canada?

PMID- 20696814
TI  - The association of the angiopoietin/Tie-2 system with the development of
      metastasis and leukocyte migration in neuroendocrine tumors.
AB  - The aim of this study was to explore the possible involvement of the angiopoietin
      (Ang)-1, -2/Tie-2 system in the development, growth, and metastases evolution of
      gastroenteropancreatic-neuroendocrine tumors (GEP-NETs). We prospectively
      examined the serum levels of Tie-2, Ang-1, and Ang-2 by ELISA in 42 patients with
      proven GEP-NETs and 27 controls. We also determined the expression of the Ang/Tie
      2 system in freshly isolated peripheral blood monocytes and in tumor cells from
      malignant primary tumors and/or liver metastases samples from GEP-NET patients by
      flow cytometry and/or RT-PCR. Furthermore, the function of the Ang/Tie-2 system
      in monocytes from controls and patients was assessed by a chemotaxis assay. GEP
      NET patients showed enhanced serum levels of soluble form of Tie-2 (sTie-2), Ang
      1, and Ang-2 (P<0.05 in all cases), compared to controls. sTie-2 and Ang-2 levels
      were significantly higher in GEP-NETs with metastases compared to those with no
      metastases. In addition, a significant correlation was detected between Ang-2
      levels and chromogranin A or sTie-2 concentrations or 5-hydroxy-indole acetic
      acid excretion (r=0.71, r=0.60, and r=0.81 respectively, P<0.01 in all cases).
      Furthermore, we observed an enhanced expression of Ang-1, Ang-2, and Tie-2 in
      freshly isolated tumor cells from GEP-NET both by immunohistochemistry and by RT
      PCR. Interestingly, an enhanced expression and function of Tie-2 was detected in
      monocytes from GEP-NET patients. Our data suggest that the Ang/Tie-2 system is
      involved in the growth and development of metastases of GEP-NETs, and that favors
      the recruitment of Tie-2(+) monocytes to the tumor site, where they can promote
      inflammation and angiogenesis.

PMID- 20696816
TI  - Radiotherapy for glottic T1N0 carcinoma with slight hypofractionation and
      standard overall treatment time: importance of overall treatment time.
AB  - OBJECTIVE: We retrospectively investigated treatment outcomes in patients with
      glottic T1 carcinoma treated with 65 Gy in 26 fractions four times a week and
      discuss the importance of the overall treatment time. METHODS: Two hundred one
      patients with glottic T1 carcinoma were evaluated. Sixty-five Gray in 26
      fractions were delivered for 200 patients, whereas 1 patient received 62.5 Gy in
      25 fractions. We delivered radiotherapy once daily four times a week in this
      period, for a weekly dose of 10 Gy. Weekdays except Wednesday were treatment
      days. RESULTS: The overall survival rate was 96.8 +/- 1.3% (standard error) at 3
      years and 90.8 +/- 2.2% at 5 years. The local control rate was 91.9 +/- 2.0% at 3
      years and 89.8 +/- 2.3% at 5 years. In patients with an overall treatment time
      equal to or longer than 47 days, the local control rate was 82.6 +/- 6.0% at both
      3 and 5 years. In the patients with overall treatment time equal to or less than
      46 days, the local control rate was 94.6 +/- 1.9% at 3 years and 91.8 +/- 2.4% at
      5 years. There was a significant difference between these two groups (P =
      0.0349). A severe late radiation reaction occurred in one patient. He experienced
      severe laryngeal edema that required tracheotomy at 6 months after the completion
      of radiotherapy. The tracheotomy was closed at 14 months after completion of
      radiotherapy. CONCLUSIONS: Overall treatment time seems to be an important factor
      for a good local control rate for glottic T1N0 carcinoma even when treated with
      slight hypofractionation.

PMID- 20696815
TI  - Feasibility and robustness of amplification refractory mutation system (ARMS)
      based KRAS testing using clinically available formalin-fixed, paraffin-embedded
      samples of colorectal cancers.
AB  - BACKGROUND: KRAS mutation testing is recommended for the discernment of
      metastatic colorectal cancer patients who are unlikely to benefit from anti
      epidermal growth factor receptor antibodies. A recently developed amplification
      refractory mutation-Scorpion system is becoming a standard method for KRAS mutant
      detection. The feasibility and robustness of this system using DNA samples from
      clinically available formalin-fixed, paraffin-embedded specimens were evaluated.
      METHODS: Genomic DNA from macro-dissected 110 specimens was applied for the KRAS
      mutant detection using a commercial amplification refractory mutation-Scorpion
      system kit. Success rate and mutant detection rate of the test were evaluated.
      RESULTS: Small intra- and inter-lot deviations of the testing kit and a good
      concordance among different real-time polymerase chain reaction systems suggested
      the reliability of the amplification refractory mutation-Scorpion system. Though
      one-third of the 110 samples that were tested did not contain a sufficient amount
      of DNA to detect a 1% concentration of mutant alleles, the mutant detection rate
      was not impaired using tumor DNA concentrated by macro-dissection. Using a higher
      amount of template DNA, which supposedly contained abundant interfering
      substances, prevented the detection of the exogenous control amplicons, resulting
      in a reduced success rate. Adjusting the template amount according to the total
      DNA concentration might reduce the failure rate. CONCLUSION: The amplification
      refractory mutation-Scorpion system with formalin-fixed, paraffin-embedded
      specimen-derived DNA samples exhibited an acceptable feasibility and robustness
      suitable for routine clinical practice.

PMID- 20696817
TI  - Presurgical targeted therapy with tyrosine kinase inhibitors for advanced renal
      cell carcinoma: clinical results and histopathological therapeutic effects.
AB  - OBJECTIVES: We retrospectively analyzed our patients with advanced renal cell
      carcinoma who underwent presurgical targeted therapy with tyrosine kinase
      inhibitors to clarify the safety and clinical benefit. The histopathological
      effect of this treatment was also examined. METHODS: Between July 2005 and
      February 2010, nine patients with advanced renal cell carcinoma who were treated
      with tyrosine kinase inhibitors before surgery were the subjects of this study.
      Consolidative surgery was considered when these tumors showed clinical response
      or stable disease while on targeted therapy without evidence of disease
      progression at other sites. RESULTS: The agents used were sorafenib in seven
      patients and sunitinib in two. The median duration of presurgical therapy was
      12.2 weeks, and seven patients had less than 4 months of treatment. Tumor
      reduction at 10-30% was obtained in all patients but one. Perioperative
      complications were observed in five of nine patients. Major complications
      occurred in two patients, including intraoperative excessive bleeding and delayed
      localized intraperitoneal abscess. Minor complications were found in three. The
      characteristics of the histopathological effect of tyrosine kinase inhibitors
      consisted of marked atrophy of the capillary sinus, confirming the
      pharmacological mechanisms of these agents. Other findings included nuclear
      pyknosis and degeneration of tumor cells. CONCLUSIONS: Presurgical targeted
      therapy with tyrosine kinase inhibitors appears to be feasible in most patients
      with advanced renal cell carcinoma. However, the indications, the clinical
      benefit and the standard protocol still remain to be determined. Therapeutic
      effects in the histology were compatible to their pharmacological effects.

PMID- 20696818
TI  - Clinical outcomes of patients with pT0 bladder cancer after radical cystectomy: a
      single-institute experience.
AB  - OBJECTIVE: To investigate the clinical outcomes of patients who underwent radical
      cystectomy for bladder cancer at a single institution and compare those who had
      pT0 specimens with those who had residual cancer. METHODS: From January 1990 to
      December 2006, 186 patients underwent radical cystectomy with or without
      neoadjuvant chemotherapy for cT2 or higher stage urothelial carcinoma in the
      bladder in our hospital. We estimated the 5-year disease-free survival, cancer
      specific survival and overall survival by the pathological stage. RESULTS: The
      median follow-up of the 186 patients was 38.5 months (0-194). Of these, 51
      received neoadjuvant chemotherapy. For all subjects, the 5-year disease-free
      survival was 54.9%, cancer-specific survival 61.0% and overall survival 57.1%. Of
      the 186 patients, 24 (12.9%) had no residual cancer in the bladder specimen at
      radical cystectomy. Of the 24 patients with pT0, only 1 (4.2%) died of bladder
      cancer. The 5-year disease-free survival, cancer-specific survival and overall
      survival rates in patients with pT0 were ~96.0%. We found pT0 histology in 11 of
      the 51 patients (21.6%) with neoadjuvant chemotherapy and in 13 of the 135
      patients (9.6%) with radical cystectomy alone (P = 0.047). CONCLUSIONS: We
      demonstrated that the outcomes of patients who underwent radical cystectomy were
      similar to those in previous reports. Patients with pT0 showed favorable outcomes
      for disease-free survival, cancer-specific survival and overall survival in our
      study. However, they should be periodically followed up because pT0 does not
      always mean cure.

PMID- 20696819
TI  - The divergent opinions of regulatory authorities on roflumilast are puzzling but
      we need new drugs for treating chronic obstructive pulmonary disease.

PMID- 20696820
TI  - Resolution of nocturnal periodic breathing in pulmonary hypertension after
      optimal treatment.

PMID- 20696821
TI  - Preferential accumulation and export of high molecular weight FGF-2 by rat
      cardiac non-myocytes.
AB  - AIMS: fibroblast growth factor-2 (FGF-2), implicated in paracrine induction of
      cardiac hypertrophy, is translated as high molecular weight (Hi-FGF-2) and low
      molecular weight (Lo-FGF-2) isoforms. Paracrine activities are assigned to Lo-FGF
      2, whereas Hi-FGF-2 is presumed to have nuclear functions. In this work, we re
      examined the latter presumption by asking whether: cardiac non-myocytes (CNMs)
      accumulate and export Hi-FGF-2 in response to pro-hypertrophic [angiotensin II
      (Ang II)] stimuli; an unconventional secretory pathway requiring activated
      caspase-1 affects Hi-FGF2 export; and secreted Hi-FGF-2 is pro-hypertrophic.
      METHODS AND RESULTS: using neonatal rat heart-derived cultures and
      immunoblotting, we show that CNMs accumulated over 90% Hi-FGF-2, at levels at
      least five-fold higher than cardiomyocytes (CMs). Pro-hypertrophic agents (Ang
      II, endothelin-1, and isoproterenol) up-regulated CNM-associated Hi-FGF-2. The
      Ang II effect was mediated by Ang II receptor-1 but not Ang II receptor-2 as it
      was blocked by losartan but not PD123319. CNM-derived Hi-FGF-2 was detected in
      two extracellular pools: in conditioned medium from Ang II-stimulated CNMs and in
      association with the cell surface/matrix, eluted with a gentle 2 M NaCl wash of
      the cell monolayer. Conditioned medium from Ang II-treated CNMs increased
      neonatal CM size, an effect prevented by anti-FGF-2-neutralizing antibodies. The
      caspase-1 inhibitor YVAD prevented the Ang II-induced release of Hi-FGF-2 to both
      extracellular pools. CONCLUSION: CNMs are major producers of Hi-FGF-2, up
      regulated by hypertrophic stimuli and exported to the extracellular environment
      by a mechanism requiring caspase-1 activity, suggesting a link to the innate
      immune response. Hi-FGF-2 is likely to promote paracrine induction of myocyte
      hypertrophy in vivo.

PMID- 20696822
TI  - Specific and nonspecific B-cell function in the small intestines of patients with
      Whipple's disease.
AB  - Whipple's disease is a chronic multisystemic infection caused by Tropheryma
      whipplei that is characterized by arthritis, weight loss, and diarrhea. The
      immunological defects in the duodenal mucosa, the site of major replication of
      the agent underlying the pathogenesis of Whipple's disease, are poorly
      understood. Mucosal immunoglobulins are essential for the defense against
      intestinal pathogens; therefore, we analyzed the B-cell response in duodenal
      specimens and sera of Whipple's disease patients. Whereas systemic immunoglobulin
      production was affected only marginally, duodenal biopsy specimens of Whipple's
      disease patients contained reduced numbers of immunoglobulin-positive plasma
      cells and secreted less immunoglobulin compared to healthy controls but showed a
      weak secretory IgA response toward T. whipplei. This T. whipplei-specific
      intestinal immune response was not observed in controls. Thus, we were able to
      demonstrate that general mucosal immunoglobulin production in Whipple's disease
      patients is impaired. However, this deficiency does not completely abolish T.
      whipplei-specific secretory IgA production that nonetheless does not protect from
      chronic infection.

PMID- 20696823
TI  - The fslE homolog, FTL_0439 (fupA/B), mediates siderophore-dependent iron uptake
      in Francisella tularensis LVS.
AB  - The Gram-negative pathogen Francisella tularensis secretes a siderophore to
      obtain essential iron by a TonB-independent mechanism. The fslABCDE locus,
      encoding siderophore-related functions, is conserved among different Francisella
      strains. In the virulent strain Schu S4, fslE is essential for siderophore
      utilization and for growth under conditions of iron limitation. In contrast, we
      found that deletion of fslE did not affect siderophore utilization by the
      attenuated live vaccine strain (LVS). We found that one of the fslE paralogs
      encoded in the LVS genome, FTL_0439 (fupA/B), was able to partially complement a
      Schu S4 DeltafslE mutant for siderophore utilization. We generated a deletion of
      fupA/B in LVS and in the LVS DeltafslE background. The DeltafupA/B mutant showed
      reduced growth under conditions of iron limitation. It was able to secrete but
      was unable to utilize siderophore. Mutation of both fupA/B and fslE resulted in a
      growth defect of greater severity. The DeltafupA/B mutants showed a replication
      defect in J774.1A cells and decreased virulence following intraperitoneal
      infection in mice. Complementation of the DeltafupA/B mutation in cis restored
      the ability to utilize siderophore and concomitantly restored virulence. Our
      results indicate that fupA/B plays a significant role in the siderophore-mediated
      iron uptake mechanism of LVS whereas fslE appears to play a secondary role.
      Variation in iron acquisition mechanisms may contribute to virulence differences
      between the strains.

PMID- 20696824
TI  - Toll-like receptor 2 deficiency results in impaired antibody responses and septic
      shock during Borrelia hermsii infection.
AB  - Overwhelming bacteremia is a leading cause of death. To understand the mechanisms
      involved in protective antibody and pathological inflammatory responses during
      bacteremia, we have been studying the murine model of Borrelia hermsii infection.
      Toll-like receptor (TLR) signaling plays an important role in generating the
      rapid anti-B. hermsii antibody responses required for the resolution of
      bacteremia. Using NF-kappaB reporter assays, we found that B. hermsii activates
      TLR2 and TLR9. However, TLR2(-/-) TLR9(-/-) mice exhibited an impairment in anti
      B. hermsii antibody responses similar to that of TLR2(-/-) mice. Moreover, the
      impairment in the antibody responses of TLR2(-/-) mice or TLR2(-/-) TLR9(-/-)
      mice coincides with an order-of-magnitude-higher bacteremia, and death results
      from septic shock, as evidenced by a dysregulated systemic cytokine response and
      characteristic organ pathology. Since TLR2 appears to be the major extracellular
      sensor stimulated by B. hermsii, we hypothesized that during elevated bacteremia
      the activation of intracellular sensors of bacteria triggers dysregulated
      inflammation in TLR2(-/-) mice. Indeed, blocking the internalization of B.
      hermsii prevented the induction of inflammatory cytokine responses in TLR2
      deficient cells. Furthermore, we found that B. hermsii activates the cytoplasmic
      sensor nucleotide-binding oligomerization domain 2 (NOD2). Macrophages deficient
      in both TLR2 and NOD2 have impaired cytokine responses to B. hermsii compared to
      cells lacking TLR2 alone, and B. hermsii-infected TLR2(-/-) NOD2(-/-) mice
      exhibited improved survival compared to TLR2(-/-) mice. These data demonstrate
      that TLR2 is critical for protective immunity and suggest that, during heightened
      bacteremia, recognition of bacterial components by intracellular sensors can lead
      to pathological inflammatory responses.

PMID- 20696825
TI  - Effect of Borrelia burgdorferi OspC at the site of inoculation in mouse skin.
AB  - The Borrelia burgdorferi surface lipoprotein OspC is a critical virulence factor,
      but its precise role in the establishment of B. burgdorferi infection remains
      unclear. To determine whether OspC affects the host response at the site of
      inoculation of the bacterium, the recruitment of macrophages and neutrophils and
      the production of cytokines were examined at the site of infection by wild-type,
      ospC mutant, and complemented mutant B. burgdorferi strains. Of the 21 cytokines
      tested, monocyte chemoattractant protein 1 (MCP-1), keratinocyte-derived
      chemokine (KC, CXCL1), and vascular endothelial growth factor (VEGF) were found
      at increased levels at the site of inoculation of B. burgdorferi, and the levels
      varied with the production of OspC at one or more time points over the 1-week
      course of infection. The kinetics of expression and the dependence on OspC
      production by B. burgdorferi varied among the cytokines. The production of KC and
      MCP-1, and the appearance of monocytic infiltrates, correlated with the presence
      of the bacteria rather than with OspC specifically. In contrast, VEGF production
      was not correlated simply to the presence of the bacteria and is influenced by
      the presence of OspC. In in vitro assays, OspC and B. burgdorferi expressing OspC
      stimulated the growth of endothelial cells more than did the controls. These data
      suggest the possibility of a novel role for OspC in the life of B. burgdorferi at
      the interface of its mammalian and tick hosts.

PMID- 20696827
TI  - Survival defects of Cryptococcus neoformans mutants exposed to human
      cerebrospinal fluid result in attenuated virulence in an experimental model of
      meningitis.
AB  - Cryptococcus neoformans is a fungal pathogen that encounters various
      microenvironments during growth in the mammalian host, including intracellular
      vacuoles, blood, and cerebrospinal fluid (CSF). Because the CSF is isolated by
      the blood-brain barrier, we hypothesize that CSF presents unique stresses that C.
      neoformans must overcome to establish an infection. We assayed 1,201 mutants for
      survival defects in growth media, saline, and human CSF. We assessed CSF-specific
      mutants for (i) mutant survival in both human bronchoalveolar lavage (BAL) fluid
      and fetal bovine serum (FBS), (ii) survival in macrophages, and (iii) virulence
      using both Caenorhabditis elegans and rabbit models of cryptococcosis. Thirteen
      mutants exhibited significant survival defects unique to CSF. The mutations of
      three of these mutants were recreated in the clinical serotype A strain H99:
      deletions of the genes for a cation ATPase transporter (ena1Delta), a putative
      NEDD8 ubiquitin-like protein (rub1Delta), and a phosphatidylinositol 4-kinase
      (pik1Delta). Mutant survival rates in yeast media, saline, and BAL fluid were
      similar to those of the wild type; however, survival in FBS was reduced but not
      to the levels in CSF. These mutant strains also exhibited decreased intracellular
      survival in macrophages, various degrees of virulence in nematodes, and severe
      attenuation of survival in a rabbit meningitis model. We analyzed the CSF by mass
      spectrometry for candidate compounds responsible for the survival defect. Our
      findings indicate that the genes required for C. neoformans survival in CSF ex
      vivo are necessary for survival and infection in this unique host environment.

PMID- 20696826
TI  - Pic, an autotransporter protein secreted by different pathogens in the
      Enterobacteriaceae family, is a potent mucus secretagogue.
AB  - A hallmark of enteroaggregative Escherichia coli (EAEC) infection is a formation
      of biofilm, which comprises a mucus layer with immersed bacteria in the
      intestines of patients. While studying the mucinolytic activity of Pic in an in
      vivo system, rat ileal loops, we surprisingly found that EAEC induced
      hypersecretion of mucus, which was accompanied by an increase in the number of
      mucus-containing goblet cells. Interestingly, an isogenic pic mutant (EAEC
      Deltapic) was unable to cause this mucus hypersecretion. Furthermore, purified
      Pic was also able to induce intestinal mucus hypersecretion, and this effect was
      abolished when Pic was heat denatured. Site-directed mutagenesis of the serine
      protease catalytic residue of Pic showed that, unlike the mucinolytic activity,
      secretagogue activity did not depend on this catalytic serine protease motif.
      Other pathogens harboring the pic gene, such as Shigella flexneri and
      uropathogenic E. coli (UPEC), also showed results similar to those for EAEC, and
      construction of isogenic pic mutants of S. flexneri and UPEC confirmed this
      secretagogue activity. Thus, Pic mucinase is responsible for one of the
      pathophysiologic features of the diarrhea mediated by EAEC and the mucoid
      diarrhea induced by S. flexneri.

PMID- 20696829
TI  - The staphylococcus-specific gene rsr represses agr and virulence in
      Staphylococcus aureus.
AB  - The expression of virulence factors in Staphylococcus aureus is tightly
      coordinated by a vast network of regulatory molecules. In this report, we
      characterize a genetic locus unique to staphylococci called rsr that has a role
      in repressing two key virulence regulators, sarR and agr. Using strain SH1000, we
      showed that the transcription of virulence effectors, such as hla, sspA, and spa,
      is altered in an rsr mutant in a way consistent with agr upregulation. Analysis
      of RNAIII expression of the agr locus in rsr and rsr-sarR mutants indicated that
      rsr likely contributes to agr expression independently of SarR. We also provide
      evidence using a murine model of S. aureus skin infection that the effects
      mediated by rsr reduce disease progression.

PMID- 20696828
TI  - Arachidonic acid metabolism regulates Escherichia coli penetration of the blood
      brain barrier.
AB  - Escherichia coli K1 meningitis occurs following penetration of the blood-brain
      barrier, but the underlying mechanisms involved in E. coli penetration of the
      blood-brain barrier remain incompletely understood. We have previously shown that
      host cytosolic phospholipase A(2)alpha (cPLA(2)alpha) contributes to E. coli
      invasion of human brain microvascular endothelial cells (HBMEC), which constitute
      the blood-brain barrier, but the underlying mechanisms remain unclear.
      cPLA(2)alpha selectively liberates arachidonic acid from membrane phospholipids.
      Here, we provide the first direct evidence that host 5-lipoxygenase and
      lipoxygenase products of arachidonic acid, cysteinyl leukotrienes (LTs),
      contribute to E. coli K1 invasion of HBMEC and penetration into the brain, and
      their contributions involve protein kinase C alpha (PKCalpha). These findings
      demonstrate that arachidonic acid metabolism regulates E. coli penetration of the
      blood-brain barrier, and studies are needed to further elucidate the mechanisms
      involved with metabolic products of arachidonic acid for their contribution to E.
      coli invasion of the blood-brain barrier.

PMID- 20696830
TI  - Enterococcal biofilm formation and virulence in an optimized murine model of
      foreign body-associated urinary tract infections.
AB  - Catheter-associated urinary tract infections (CAUTIs) constitute the majority of
      nosocomial UTIs and pose significant clinical challenges. Enterococcal species
      are among the predominant causative agents of CAUTIs. However, very little is
      known about the pathophysiology of Enterococcus-mediated UTIs. We optimized a
      murine model of foreign body-associated UTI in order to mimic conditions of
      indwelling catheters in patients. In this model, the presence of a foreign body
      elicits major histological changes and induces the expression of several
      proinflammatory cytokines in the bladder. In addition, in contrast to naive mice,
      infection of catheter-implanted mice with Enterococcus faecalis induced the
      specific expression of interleukin 1beta (IL-1beta) and macrophage inflammatory
      protein 1alpha (MIP-1alpha) in the bladder. These responses resulted in a
      favorable niche for the development of persistent E. faecalis infections in the
      murine bladders and kidneys. Furthermore, biofilm formation on the catheter
      implant in vivo correlated with persistent infections. However, the enterococcal
      autolytic factors GelE and Atn (also known as AtlA), which are important in
      biofilm formation in vitro, are dispensable in vivo. In contrast, the
      housekeeping sortase A (SrtA) is critical for biofilm formation and virulence in
      CAUTIs. Overall, this murine model represents a significant advance in the
      understanding of CAUTIs and underscores the importance of urinary catheterization
      during E. faecalis uropathogenesis. This model is also a valuable tool for the
      identification of virulence determinants that can serve as potential
      antimicrobial targets for the treatment of enterococcal infections.

PMID- 20696831
TI  - Sublingual immunization protects against Helicobacter pylori infection and
      induces T and B cell responses in the stomach.
AB  - Sublingual (SL) immunization has been described as an effective novel way to
      induce mucosal immune responses in the respiratory and genital tracts. We
      examined the potential of SL immunization against Helicobacter pylori to
      stimulate immune responses in the gastrointestinal mucosa and protect against H.
      pylori infection. Mice received two SL immunizations with H. pylori lysate
      antigens and cholera toxin as an adjuvant, and after challenge with live H.
      pylori bacteria, their immune responses and protection were evaluated, as were
      immune responses prior to challenge. SL immunization induced enhanced
      proliferative responses to H. pylori antigens in cervicomandibular lymph nodes
      and provided at least the same level of immune responses and protection as
      corresponding intragastric immunization. Protection in SL-immunized mice was
      associated with strong H. pylori-specific serum IgG and IgA antibody responses in
      the stomach and intestine, with strong proliferation and gamma interferon (IFN
      gamma) and interleukin-17 (IL-17) production by spleen and mesenteric lymph node
      T cells stimulated with H. pylori antigens in vitro, and with increased IFN-gamma
      and IL-17 gene expression in the stomach compared to levels in infected
      unimmunized mice. Immunohistochemical studies showed enhanced infiltration of
      CD4(+) T cells and CD19(+) B cells into the H. pylori-infected stomach mucosa of
      SL-immunized but not unimmunized H. pylori-infected mice, which coincided with
      increased expression of the mucosal addressin cell adhesion molecule (MAdCAM-1)
      and T and B cell-attracting chemokines CXCL10 and CCL28. We conclude that, in
      mice, SL immunization can effectively induce protection against H. pylori
      infection in association with strong T and B cell infiltration into the stomach.

PMID- 20696832
TI  - Allele specificity of gamma interferon responses to the carboxyl-terminal region
      of Plasmodium falciparum merozoite surface protein 1 by Kenyan adults with
      naturally acquired immunity to malaria.
AB  - Cross-sectional seroepidemiological studies of populations naturally exposed to
      Plasmodium falciparum suggest an association between protection from malaria and
      circulating antibodies to the carboxyl terminus of merozoite surface protein 1
      (MSP1). Questions remain regarding the significance of cell-mediated immunity to
      MSP1 in conferring protection and inducing immunologic memory. Vaccine constructs
      have been based on the 42-kDa recombinant MSP1 protein (MSP1(42)), which includes
      the 19-kDa (MSP1(19)) and 33-kDa (MSP1(33)) fragments containing the major B- and
      T-cell epitopes, respectively. To evaluate T-cell responses to the MSP1(33)
      fragment, two libraries of overlapping 18-mer peptides from the 3D7 and FVO
      MSP1(33) regions were used to screen a cohort of asymptomatic Kenyan adults.
      Gamma interferon (IFN-gamma) measured by enzyme-linked immunospot assay (ELISPOT)
      at multiple time points assessed the magnitude and stability of these responses.
      The percentage of individuals with IFN-gamma responses to single MSP1(33)
      peptides ranged from nil to 24%, were clustered among a subset of peptides, and
      were not consistently recalled over time. In comparison to peptide responses, IFN
      gamma ELISPOT responses to recombinant MSP1(42) were more prevalent, more
      frequently elicited by the 3D7 as opposed to the FVO allele, and more stable over
      time. The prevailing MSP1(33) genotype infection was 3D7, with few mixed
      infections and no sole FVO infections. This study demonstrates that immunity
      against MSP1(33) after cumulative natural infections consists of low-magnitude
      and difficult-to-detect IFN-gamma responses. Although immunity against MSP1 alone
      will not confer protection against malaria, demonstrating a relative and
      sustained increase in T-cell immunity to MSP1 after vaccination would be a
      reasonable measurement of vaccine responsiveness.

PMID- 20696833
TI  - Characterization of unique regions of Borrelia burgdorferi surface-located
      membrane protein 1.
AB  - The pathogen of Lyme disease, Borrelia burgdorferi, produces a putative surface
      protein termed "surface-located membrane protein 1" (Lmp1). Lmp1 has been shown
      previously to assist the microbe in evasion of host-acquired immune defenses and
      in the establishment of persistent infection of mammals. Here, we show that Lmp1
      is an integral membrane protein with surface-exposed N-terminal, middle, and C
      terminal regions. During murine infection, antibodies recognizing these three
      protein regions were produced. Separate immunization of mice with each of the
      discrete regions exerted differential effects on spirochete survival during
      infection. Notably, antibodies against the C-terminal region primarily interfered
      with B. burgdorferi persistence in the joints, while antibodies specific to the N
      terminal region predominantly affected pathogen levels in the heart, including
      the development of carditis. Genetic reconstitution of lmp1 deletion mutants with
      the lmp1 N-terminal region significantly enhanced its ability to resist the
      bactericidal effects of immune sera and also was observed to increase pathogen
      survival in vivo. Taken together, the combined data suggest that the N-terminal
      region of Lmp1 plays a distinct role in spirochete survival and other parts of
      the protein are related to specific functions corresponding to pathogen
      persistence and tropism during infection that is displayed in an organ-specific
      manner. The findings reported here underscore the fact that surface-exposed
      regions of Lmp1 could potentially serve as vaccine targets or antigenic regions
      that could alter the course of natural Lyme disease.

PMID- 20696834
TI  - Platelet activation and biofilm formation by Aerococcus urinae, an endocarditis
      causing pathogen.
AB  - The Gram-positive bacterium Aerococcus urinae can cause infectious endocarditis
      (IE) in older persons. Biofilm formation and platelet aggregation are believed to
      contribute to bacterial virulence in IE. Five A. urinae isolates from human blood
      were shown to form biofilms in vitro, and biofilm formation was enhanced by the
      presence of human plasma. Four of the A. urinae isolates caused platelet
      aggregation in platelet-rich plasma from healthy donors. The Au3 isolate, which
      induced platelet aggregation in all donors, also activated platelets, as
      determined by flow cytometry. Platelet aggregation was dependent on bacterial
      protein structures and on platelet activation since it was sensitive to both
      trypsin and prostaglandin E(1). Plasma proteins at the bacterial surface were
      needed for platelet aggregation; and roles of the complement system, fibrinogen,
      and immunoglobulin G were demonstrated. Complement-depleted serum was unable to
      support platelet aggregation by Au3 and complement blockade using compstatin
      inhibited platelet activation. Platelet activation by Au3 was inhibited by
      blocking of the platelet fibrinogen receptor, and this isolate was also shown to
      bind to radiolabeled fibrinogen. Removal of IgG from platelet-rich plasma by a
      specific protease inhibited the platelet aggregation induced by A. urinae, and
      blockade of the platelet FcRgammaIIa hindered platelet activation induced by Au3.
      Convalescent-phase serum from a patient with A. urinae IE transferred the ability
      of the bacterium to aggregate platelets in an otherwise nonresponsive donor. Our
      results show that A. urinae exhibits virulence strategies of importance for IE.

PMID- 20696835
TI  - Invasion and multiplication of Helicobacter pylori in gastric epithelial cells
      and implications for antibiotic resistance.
AB  - Helicobacter pylori is a Gram-negative, spiral-shaped bacterium that infects more
      than 50% of the human population and can cause gastritis, peptic ulcer, or
      gastric malignancies. It is generally viewed as an extracellular microorganism.
      In a gentamicin protection assay on AGS or MKN45 cells, H. pylori could invade
      the epithelial cells and multiply within double-layer vesicles either on the
      plasma membrane or in the cytoplasm. A 5-fold increase in the number of bacteria
      was recultured from the infected cells at 12 h, compared with the number of
      invading cells at 2.5 h postinfection. The autophagic vesicles induced by H.
      pylori are the sites of replication and also of the degradation of the
      replicating bacteria after fusion with lysosomes. Many H. pylori bacteria in
      coccoid form associated with the plasma membrane can be released into culture.
      Only cell-penetrating antibiotics can enhance the intracellular killing of the
      replicating bacteria. The multiplication of H. pylori within cells provides a
      niche for its resistance to antibacterial therapy and has a significant impact on
      its biological life cycle.

PMID- 20696836
TI  - Trypanosoma cruzi-induced activation of functionally distinct alphabeta and
      gammadelta CD4- CD8- T cells in individuals with polar forms of Chagas' disease.
AB  - CD4(-) CD8(-) (double-negative [DN]) T cells have recently been shown to display
      important immunological functions in human diseases. They express gammadelta or
      alphabeta T-cell receptors that recognize lipid/glycolipid antigens presented via
      the nonclassical major histocompatibility complex molecules of the CD1 family. We
      recently demonstrated that while alphabeta DN T cells serve primarily to express
      inflammatory cytokines, gammadelta DN T cells express mainly interleukin-10 (IL
      10) in patients with cutaneous leishmaniasis. We also demonstrated a correlation
      between DN T cells and the expression of gamma interferon in the acute phase of
      Trypanosoma cruzi experimental infection. In this work, we sought to investigate
      whether alphabeta or gammadelta DN T cells display distinct immunoregulatory
      potentials in patients with polar forms of human Chagas' disease. Our data showed
      that in vitro infection with T. cruzi leads to expansion of DN T cells in
      patients with the indeterminate and severe cardiac clinical forms of the disease.
      However, while alphabeta DN T cells primarily produce inflammatory cytokines in
      both forms of the disease, gammadelta DN T cells display a marked, significant
      increase in antigen-specific IL-10 expression in indeterminate patients relative
      to cardiac patients. Finally, higher frequencies of the IL-10-producing
      gammadelta DN T cells were correlated with improved clinical measures of cardiac
      function in the patients, suggesting a protective role for these cells in Chagas'
      disease. Taken together, these data show distinct functional characteristics for
      alphabeta and gammadelta DN T cells associated with distinct morbidity rates and
      clinical forms in human Chagas' disease.

PMID- 20696837
TI  - Architectural epigenetics: mitotic retention of mammalian transcriptional
      regulatory information.
AB  - Epigenetic regulatory information must be retained during mammalian cell division
      to sustain phenotype-specific and physiologically responsive gene expression in
      the progeny cells. Histone modifications, DNA methylation, and RNA-mediated
      silencing are well-defined epigenetic mechanisms that control the cellular
      phenotype by regulating gene expression. Recent results suggest that the mitotic
      retention of nuclease hypersensitivity, selective histone marks, as well as the
      lineage-specific transcription factor occupancy of promoter elements contribute
      to the epigenetic control of sustained cellular identity in progeny cells. We
      propose that these mitotic epigenetic signatures collectively constitute
      architectural epigenetics, a novel and essential mechanism that conveys
      regulatory information to sustain the control of phenotype and proliferation in
      progeny cells by bookmarking genes for activation or suppression.

PMID- 20696838
TI  - Dosage-sensitive regulation of cohesin chromosome binding and dynamics by Nipped
      B, Pds5, and Wapl.
AB  - The cohesin protein complex holds sister chromatids together to ensure proper
      chromosome segregation upon cell division and also regulates gene transcription.
      Partial loss of the Nipped-B protein that loads cohesin onto chromosomes, or the
      Pds5 protein required for sister chromatid cohesion, alters gene expression and
      organism development, without affecting chromosome segregation. Knowing if a
      reduced Nipped-B or Pds5 dosage changes how much cohesin binds chromosomes, or
      the stability with which it binds, is critical information for understanding how
      cohesin regulates transcription. We addressed this question by in vivo
      fluorescence recovery after photobleaching (FRAP) with Drosophila salivary
      glands. Cohesin, Nipped-B, and Pds5 all bind chromosomes in both weak and stable
      modes, with residence half-lives of some 20 seconds and 6 min, respectively.
      Reducing the Nipped-B dosage decreases the amount of stable cohesin without
      affecting its chromosomal residence time, and reducing the Pds5 dosage increases
      the amount of stable cohesin. This argues that Nipped-B and Pds5 regulate
      transcription by controlling how much cohesin binds DNA in the stable mode, and
      not binding affinity. We also found that Nipped-B, Pds5, and the Wapl protein
      that interacts with Pds5 all play unique roles in cohesin chromosome binding.

PMID- 20696839
TI  - Cell-type-specific activation and repression of PU.1 by a complex of discrete,
      functionally specialized cis-regulatory elements.
AB  - The transcription factor PU.1 is critical for multiple hematopoietic lineages,
      but different leukocyte types require strictly distinct patterns of PU.1
      regulation. PU.1 is required early for T-cell lineage development but then must
      be repressed by a stage-specific mechanism correlated with commitment. Other
      lineages require steady, low expression or upregulation. Until now, only the
      promoter plus a distal upstream regulatory element (URE) could be invoked to
      explain nearly all Sfpi1 (PU.1) activation and repression, including bifunctional
      effects of Runx1. However, the URE is dispensable for most Sfpi1 downregulation
      in early T cells, and we show that it retains enhancer activity in immature T
      lineage cells even where endogenous Sfpi1 is repressed. We now present evidence
      for another complex of conserved noncoding elements that mediate discrete, cell
      type-specific regulatory features of Sfpi1, including a myeloid cell-specific
      activating element and a separate, pro-T-cell-specific silencer element. These
      elements yield opposite, cell-type-specific responses to Runx1. T-cell-specific
      repression requires Runx1 acting through multiple nonconsensus sites in the
      silencer core. These newly characterized sites recruit Runx1 binding in early T
      cells in vivo and define a functionally specific scaffold for dose-dependent,
      Runx-mediated repression.

PMID- 20696840
TI  - Mechanism of hypoxia-induced NF-kappaB.
AB  - NF-kappaB activation is a critical component in the transcriptional response to
      hypoxia. However, the underlying mechanisms that control its activity under these
      conditions are unknown. Here we report that under hypoxic conditions, IkappaB
      kinase (IKK) activity is induced through a calcium/calmodulin-dependent kinase 2
      (CaMK2)-dependent pathway distinct from that for other common inducers of NF
      kappaB. This process still requires IKK and the IKK kinase TAK1, like that for
      inflammatory inducers of NF-kappaB, but the TAK1-associated proteins TAB1 and
      TAB2 are not essential. IKK complex activation following hypoxia requires Ubc13
      but not the recently identified LUBAC (linear ubiquitin chain assembly complex)
      ubiquitin conjugation system. In contrast to the action of other NF-kappaB
      inducers, IKK-mediated phosphorylation of IkappaBalpha does not result in its
      degradation. We show that this results from IkappaBalpha sumoylation by Sumo-2/3
      on critical lysine residues, normally required for K-48-linked
      polyubiquitination. Furthermore, inhibition of specific Sumo proteases is
      sufficient to release RelA from IkappaBalpha and activate NF-kappaB target genes.
      These results define a novel pathway regulating NF-kappaB activation, important
      to its physiological role in human health and disease.

PMID- 20696841
TI  - RhoA phosphorylation induces Rac1 release from guanine dissociation inhibitor
      alpha and stimulation of vascular smooth muscle cell migration.
AB  - Although overactivation of RhoA is recognized as a common component of vascular
      disorders, the molecular mechanisms regulating RhoA activity in vascular smooth
      muscle cells (VSMC) are still unclear. We have previously shown that in VSMC,
      RhoA is phosphorylated on Ser188 by nitric oxide (NO)-stimulated cGMP-dependent
      kinase (PKG), which leads to RhoA-Rho kinase pathway inhibition. In this study,
      we showed that expression of phosphoresistant RhoA mutants prevented the
      stimulation of VSMC migration and adhesion induced by NO-PKG pathway activation.
      In contrast, under basal conditions, phosphomimetic RhoA mutants stimulated VSMC
      adhesion and migration through a signaling pathway requiring Rac1 and the Rho
      exchange factor Vav3. RhoA phosphorylation or phosphomimetic RhoA mutants induced
      Rac1 activation but did not activate Vav3. Indeed, phosphorylated RhoA or
      phosphomimetic mutants trapped guanine dissociation inhibitor alpha (GDIalpha),
      leading to the release of Rac1 and its translocation to the membrane, where it
      was then activated by the basal Vav3 nucleotide exchange activity. In vivo, RhoA
      phosphorylation induced by PKG activation in the aortas of rats treated with
      sildenafil induced dissociation of Rac1 from GDIalpha and activation of the Rac1
      signaling pathway. These results suggest that the phosphorylation of RhoA
      represents a novel potent and physiological GDIalpha displacement factor that
      leads to Rac1 activation and regulation of Rac1-dependent VSMC functions.

PMID- 20696844
TI  - Effects of workplace bullying on how women work.
AB  - Work is central to well-being but working is problematic when people experience
      workplace bullying, which includes psychological, physical, and sexual abuse or
      harassment. The purpose of the present grounded theory study was to extend
      current understanding, from the perspective of women, of how workplace bullying
      affects their work and how they engage in the workforce. The study was conducted
      in eastern Canada with 36 English-speaking women who had been bullied in the
      workplace. They reported mainly psychological bullying. The central problem for
      women is they cannot continue working as they had before the workplace bullying.
      The authors named a four-stage process of how women address this problem as
      "Doing Work Differently." The four stages are Being Conciliatory, Reconsidering,
      Reducing Interference, and Redeveloping Balance. The process is influenced by
      women's support systems, the effects on their health, and financial
      circumstances. There are implications for public education, workplace policies,
      and health care workers.

PMID- 20696842
TI  - CD69 association with Jak3/Stat5 proteins regulates Th17 cell differentiation.
AB  - T-cell differentiation involves the early decision to commit to a particular
      pattern of response to an antigen. Here, we show that the leukocyte activation
      antigen CD69 limits differentiation into proinflammatory helper T cells (Th17
      cells). Upon antigen stimulation in vitro, CD4(+) T cells from CD69-deficient
      mice generate an expansion of Th17 cells and the induction of greater mRNA
      expression of interleukin 17 (IL-17), IL 23 receptor (IL-23R), and the nuclear
      receptor retinoic acid-related orphan receptor gammat (RORgammat). In vivo
      studies with CD69-deficient mice bearing OTII T-cell receptors (TCRs) specific
      for OVA peptide showed a high proportion of antigen-specific Th17 subpopulation
      in the draining lymph nodes, as well as in CD69-deficient mice immunized with
      type II collagen. Biochemical analysis demonstrated that the CD69 cytoplasmic
      tail associates with the Jak3/Stat5 signaling pathway, which regulates the
      transcription of RORgammat and, consequently, differentiation toward the Th17
      lineage. Functional experiments in Th17 cultures demonstrated that the selective
      inhibition of Jak3 activation enhanced the transcription of RORgammat. Moreover,
      the addition of exogenous IL-2 restored Stat5 phosphorylation and inhibited the
      enhanced Th17 differentiation in CD69-deficient cells. These results support the
      early activation receptor CD69 as an intrinsic modulator of the T-cell
      differentiation program that conditions immune inflammatory processes.

PMID- 20696845
TI  - Predictors of health-related quality of life among low-income midlife women.
AB  - The purpose of this study was to determine whether any of the sociodemographic,
      biomedical, psychosocial, and medical-care factors independently predict health
      related quality of life (HRQoL) among low-income women. Cross-sectional data were
      used to predict factors that determine HRQoL. A survey was conducted targeting a
      convenience sample of 200 midlife women. Blood samples were drawn from all
      participants, who also received a physical examination. Hierarchical multiple
      regression analysis was used to test the independent effects of each factor. The
      study found that sociodemographic and psychosocial factors were independently
      associated with HRQoL. Compared to married women, widowed or divorced women had
      significantly lower HRQoL, whereas those with higher levels of stress perception
      and those not performing regular exercise had significantly lower HRQoL (p <
      .01). The full model accounted for 44.7% of the variance in HRQoL. The HRQoL of
      low-income midlife women was associated with multiple factors, with stress
      perception exerting the major influence.

PMID- 20696843
TI  - The atypical homeodomain transcription factor Mohawk controls tendon
      morphogenesis.
AB  - The Mohawk homeobox (Mkx) gene encodes a new atypical homeodomain-containing
      protein with transcriptional repressor activity. Mkx mRNA exhibited dynamic
      expression patterns during development of the palate, somite, kidney, and testis,
      suggesting that it may be an important regulator of multiple developmental
      processes. To investigate the roles of Mkx in organogenesis, we generated mice
      carrying a null mutation in this gene. Mkx(-/-) mice survive postnatally and
      exhibit a unique wavy-tail phenotype. Close examination revealed that the mutant
      mice had smaller tendons than wild-type littermates and that the rapid postnatal
      growth of collagen fibrils in tendons was disrupted in Mkx(-/-) mice. Defects in
      tendon development were detected in the mutant mouse embryos as early as
      embryonic day 16.5 (E16.5). Although collagen fibril assembly initially appeared
      normal, the tendons of Mkx(-/-) embryos expressed significantly reduced amounts
      of collagen I, fibromodulin, and tenomodulin in comparison with control
      littermates. We found that Mkx mRNA was strongly expressed in differentiating
      tendon cells during embryogenesis and in the tendon sheath cells in postnatal
      stages. In addition to defects in tendon collagen fibrillogenesis, Mkx(-/-)
      mutant mice exhibited abnormal tendon sheaths. These results identify Mkx as an
      important regulator of tendon development.

PMID- 20696846
TI  - Factors influencing prostate cancer screening in African American men.
AB  - African American men have the highest prostate cancer incidence and mortality
      rates worldwide, but have lower screening rates compared with Caucasian men. The
      purpose of the study was to identify social ecological factors that affect
      screening behaviors in African American men, knowledge that could be integral to
      the design of culturally appropriate interventions. The exploratory study
      included 60 African American males recruited from the greater Detroit
      metropolitan area. Social ecological variables examined included age, marital
      status, presence of health insurance, education, health values and behaviors,
      physician trust, and perceived stress coping (John Henryism). Analyses included
      descriptives, chi-square tests, one-way ANOVAs, and logistic regression. Findings
      concluded that a parsimonious model consisting of two variables (age and health
      values) was predictive. African American males, > or =50 years, with higher
      positive health values were more likely to obtain screening. Findings imply the
      importance of health values and targeted educational and screening interventions
      for younger African American men.

PMID- 20696847
TI  - The experience of stress for open heart surgery patients and their caregivers.
AB  - The purpose of this research was to understand the modern experience of stress
      among adult coronary artery bypass grafting (CABG) patients who are hospitalized
      less than 10 days and among their significant caregivers. The naming of stressors
      and the nature and triggers for the stress response that either contributed to or
      ameliorated stress were examined. A qualitative research method using hermeneutic
      phenomenology was used to interpret and understand the experience of stress. The
      stressors identified by both patient and family participants in this study were
      shock and disbelief leading to a feeling of being overwhelmed. Among patients,
      mortality was foremost. Among family caregivers, anger was expressed. The
      importance of providing information, honesty, and trust were pivotal to
      alleviating stress. A more thorough knowledge of history and complementary
      therapies are needed to reduce stress.

PMID- 20696848
TI  - History of the modern epidemiological concept of confounding.
AB  - The epidemiological concept of confounding has had a convoluted history. It was
      first expressed as an issue of group non-comparability, later as an uncontrolled
      fallacy, then as a controllable fallacy named confounding, and, more recently, as
      an issue of group non-comparability in the distribution of potential outcome
      types. This latest development synthesised the apparent disconnect between phases
      of the history of confounding. Group non-comparability is the essence of
      confounding, and the statistical fallacy its consequence. This essay discusses
      how confounding was perceived in the 18th and 19th centuries, reviews how the
      concept evolved across the 20th century and finally describes the modern
      definition of confounding.

PMID- 20696849
TI  - Effect of changes in season and temperature on mortality associated with air
      pollution in Seoul, Korea.
AB  - BACKGROUNDS: Global warming has increased concern about the synergistic or
      interactive effects of temperature and air pollution on human health. The aim of
      this study was to examine the effect of changes in season and temperature on
      mortality associated with air pollution in Seoul, Korea, from June 1999 to
      December 2007. METHODS: We used Poisson regression models with natural cubic
      splines. The effect of modifications was explored with two models: a time-varying
      coefficient model and a temperature-stratified model. RESULTS: In the summer
      season with high temperatures, we observed a considerable increase in the
      association between mortality and air pollution. The elevated risk was pronounced
      particularly in the effect of SO2, and the increase of RR on non-accidental
      mortality was 0.83% (95% CI 0.42 to 1.25) at high temperatures (>= 26.2 degrees
      C) whereas the overall estimate was 0.21% (95% CI 0.07 to 0.36) per 0.5 ppb
      increment of SO2. Those aged 65 y and over generally showed a higher risk of
      mortality. At extremely high temperature, the age group 85 y and older was
      especially vulnerable to air pollution. In a two-pollutant model, the significant
      effect of SO2 at high temperatures (>= 26.2 degrees C) was not confounded by
      adjusting for other pollutants and the effect of CO at temperatures of 19.1-26.2
      degrees C remained largely unchanged by adjusting for other pollutants. The
      dominant adverse effect of SO2 at high temperatures might be explained by an
      increase in concentration of sulfates by enhanced photochemical reaction, whereas
      at milder temperatures without vigorous photochemical activity the effect of CO
      may predominate in increasing mortality. CONCLUSIONS: Season and temperature
      strongly modified the adverse effect of air pollution, which implicates that an
      increase in the number of hot summer days by global warming may alter the health
      effects of air pollution.

PMID- 20696850
TI  - The choriocarcinoma cell line BeWo: syncytial fusion and expression of syncytium
      specific proteins.
AB  - Fusion of the trophoblast-derived choriocarcinoma cell line BeWo can be triggered
      by forskolin. BeWo cells are regularly used as a cell culture model to mimic in
      vivo syncytialisation of placental villous trophoblast. The beta subunit of human
      chorionic gonadotropin (CGB), placental alkaline phosphatase as well as placental
      protein 13 (PP13, LGALS13) are exclusively expressed in the syncytiotrophoblast
      of the human placenta, and CGB is commonly used as a marker of syncytial
      differentiation. Here we tested the hypothesis that syncytial fusion precedes CGB
      and LGALS13 expression in trophoblast-derived BeWo cells. BeWo cells were
      cultured for 48 h in the presence or absence of forskolin and varying
      concentrations of H-89, a protein kinase A inhibitor that interferes with the
      forskolin-mediated pathway of syncytial fusion. LGALS13 and CGB expression were
      quantified by DELFIA and real-time PCR. Cell fusion was determined by
      morphological analysis and cell counting after immunofluorescence staining. In
      forskolin-stimulated BeWo cells that were hindered to fuse by treatment with H
      89, levels of CGB protein expression were not altered, while LGALS13 protein and
      mRNA expression decreased significantly to control levels without forskolin. The
      LGALS13 protein expression data coincided with a significant decrease in
      syncytial fusion, while CGB protein expression was unaffected by rates of cell
      fusion and proliferation. We postulate that CGB protein expression is not
      necessarily linked to syncytial fusion, and thus CGB should be used with great
      caution as a marker of BeWo cell fusion.

PMID- 20696851
TI  - Selectivity in the transport of spermatozoa to oviductal reservoirs in the
      menstruating fruit bat, Carollia perspicillata.
AB  - To better document the timing of ovulation and fertilization, female reproductive
      tracts were collected every 12 h from captive-bred fruit bats (Carollia
      perspicillata) on days 1-3 postcoitum and examined histologically. This also
      permitted observations on sperm transport, storage, and disposition. As the
      animals had previously been sexually segregated, most had been cycling and
      possessed menstrual uteri at the time of collection. Menstruation is
      periovulatory in this species. A widespread, headfirst orientation of spermatozoa
      to the uterine mucosa was observed in specimens apparently collected soon after
      insemination. Thereafter, however, this relationship was limited in most cases to
      the area around the entrance of each uterotubal junction (UTJ). A small number of
      spermatozoa also colonized the UTJs, which functioned as temporary sperm
      reservoirs on days 1-2. Although C. perspicillata is monovular, no consistent
      differences were observed between the two oviducts in the pattern of sperm
      storage and release. Very few sperm were ever observed in the isthmus or ampulla
      (the site of fertilization). Menstrual debris (including fine particulate matter)
      and leukocytes present in the uterine cavity in most tracts did not gain access
      to the UTJ with the spermatozoa. Smooth muscle and abundant elastic fibers in the
      wall of the intramural UTJ, as well as receptors on its luminal epithelial cells,
      may play roles in the selective transport of spermatozoa to the fertilization
      site. While some spermatozoa are phagocytosed in the uterine lumen or by
      epithelial cells in the UTJ, the fate of most is probably expulsion into the
      vagina.

PMID- 20696852
TI  - The heartbrake of social rejection: heart rate deceleration in response to
      unexpected peer rejection.
AB  - Social relationships are vitally important in human life. Social rejection in
      particular has been conceptualized as a potent social cue resulting in feelings
      of hurt. Our study investigated the psychophysiological manifestation of hurt
      feelings by examining the beat-by-beat heart rate response associated with the
      processing of social rejection. Study participants were presented with a series
      of unfamiliar faces and were asked to predict whether they would be liked by the
      other person. Following each judgment, participants were provided with feedback
      indicating that the person they had viewed had either accepted or rejected them.
      Feedback was associated with transient heart rate slowing and a return to
      baseline that was considerably delayed in response to unexpected social
      rejection. Our results reveal that the processing of unexpected social rejection
      is associated with a sizable response of the parasympathetic nervous system.
      These findings are interpreted in terms of a cardiovagal manifestation of a
      neural mechanism implicated in the central control of autonomic function during
      cognitive processes and affective regulation.

PMID- 20696853
TI  - Delayed reentrant processing impairs visual awareness: an object-substitution
      masking study.
AB  - In object-substitution masking (OSM), a sparse, common-onset mask impairs
      perception of a target when the mask's offset is later than the target's offset
      and spatial attention is dispersed. OSM is thought to reflect the interaction of
      feed-forward and reentrant processes in the brain: Upon stimulus presentation, a
      low-resolution representation of the target and mask progresses from sensory to
      anterior brain regions, triggering reentrant processing to confirm stimulus
      identity. It is hypothesized that dispersing spatial attention prolongs the
      required reentrant iterations, increasing the likelihood that only the lingering
      mask stimulus will remain physically present and thus substitute for the target
      in consciousness. However, empirically, it remains unclear whether substitution
      stems from delayed feed-forward or reentrant processing. Here, we demonstrate
      that delayed reentrant processing causes OSM, by showing that a task tapping high
      level brain regions involved in reentrant processing leads to a spatially
      attended target being replaced by the mask. Our results confirm a key role for
      reentrant processing in conscious perception.

PMID- 20696854
TI  - Emotion differentiation as resilience against excessive alcohol use: an
      ecological momentary assessment in underage social drinkers.
AB  - Some people are adept at using discrete emotion categories (anxious, angry, sad)
      to capture their felt experience; other people merely communicate how good or bad
      they feel. We theorized that people who are better at describing their emotions
      might be less likely to self-medicate with alcohol. During a 3-week period, 106
      underage social drinkers used handheld computers to self-monitor alcohol intake.
      From participants' reported experiences during random prompts, we created an
      individual difference measure of emotion differentiation. Results from a 30-day
      timeline follow-back revealed that people with intense negative emotions consumed
      less alcohol if they were better at describing emotions and less reliant on
      global descriptions. Results from ecological momentary assessment procedures
      revealed that people with intense negative emotions prior to drinking episodes
      consumed less alcohol if they were better at describing emotions. These findings
      provide support for a novel methodology and dimension for understanding the
      influence of emotions on substance-use patterns.

PMID- 20696855
TI  - Combining resonance energy transfer methods reveals a complex between the alpha2A
      adrenergic receptor, Galphai1beta1gamma2, and GRK2.
AB  - Traditionally, G-protein-coupled receptor (GPCR) interactions with their G
      proteins and regulatory proteins, GPCR kinases (GRKs) and arrestins, are
      described as sequential events involving rapid assemblies/disassemblies. To
      directly monitor the dynamics of these interactions in living cells, we combined
      two spectrally resolved bioluminescence and one fluorescence resonance energy
      transfer (RET) methods. The RET combination analysis revealed that stimulation of
      the alpha(2A)-adrenergic receptor (alpha(2A)AR) leads to the recruitment of GRK2
      at a receptor still associated with the Galpha(i1)beta(1)gamma(2) complex. The
      interaction kinetics of GRKs with Ggamma(2) (2.8 +/- 0.4 s) and alpha(2A)AR (5.2
      +/- 0.5 s) were similar to that of the receptor-promoted change in RET between
      Galpha(i1) and Ggamma(2) (5.2 +/- 1.2 s), and persisted until the translocation
      of betaarrestin2 to the receptor, indicating that GRK2 remains associated to the
      receptor/G-protein complex for longer periods than anticipated. Moreover, GRK2 or
      a kinase-deficient GRK2 mutant, but not GRK5, potentiated the receptor-promoted
      changes in RET between Galpha(i1) and Ggamma(2) and abrogated the alpha(2A)AR
      stimulated calcium response, suggesting that the recruitment of GRK2 to the
      complex contributes to the structural rearrangement and functional regulation of
      the signaling unit, independently of the kinase activity. RET combination
      analysis revealed unanticipated dynamics in GPCR signaling and will be applicable
      to many biological systems.

PMID- 20696857
TI  - The antimicrobial peptide cathelicidin enhances activation of lung epithelial
      cells by LPS.
AB  - Epithelial cells (ECs) are usually hyporesponsive to various microbial products.
      Detection of lipopolysaccharide (LPS), the major component of gram-negative
      bacteria, is impeded, at least in part, by intracellular sequestration of its
      receptor, Toll-like receptor-4 (TLR4). In this study, using human bronchial ECs
      (hBECs) as a model of mucosal epithelium, we tested the hypothesis that the human
      LPS-binding, membrane-active cationic host defense peptide cathelicidin LL-37
      augments epithelial response to LPS by facilitating its delivery to TLR4
      containing intracellular compartments. We found that LL-37 significantly
      increases uptake of LPS by ECs with subsequent targeting to cholera toxin subunit
      B-labeled structures and lysosomes. This uptake is peptide specific, dose and
      time dependent, and involves the endocytotic machinery, functional lipid rafts,
      and epidermal growth factor receptor signaling. Cathelicidin-dependent LPS
      internalization resulted in significant increased release of the inflammatory
      cytokines IL-6 and IL-8. This indicates that, in ECs, this peptide may replace
      LPS-binding protein functions. In polarized ECs, the effect of LL-37 was
      restricted to the basolateral compartment of the epithelial membrane, suggesting
      that LL-37-mediated activation of ECs by LPS may be relevant to disease
      conditions associated with damage to the epithelial barrier. In summary, our
      study identified a novel role of LL-37 in host-microbe interactions as a host
      factor that licenses mucosal ECs to respond to LPS.

PMID- 20696856
TI  - Flavokawain B, the hepatotoxic constituent from kava root, induces GSH-sensitive
      oxidative stress through modulation of IKK/NF-kappaB and MAPK signaling pathways.
AB  - Kava (Piper methysticum Foster, Piperaceae) organic solvent-extract has been used
      to treat mild to moderate anxiety, insomnia, and muscle fatigue in Western
      countries, leading to its emergence as one of the 10 best-selling herbal
      preparations. However, several reports of severe hepatotoxicity in kava consumers
      led the U.S. Food and Drug Administration and authorities in Europe to restrict
      sales of kava-containing products. Herein we demonstrate that flavokawain B
      (FKB), a chalcone from kava root, is a potent hepatocellular toxin, inducing cell
      death in HepG2 (LD(50)=15.3 +/- 0.2 MUM) and L-02 (LD(50)=32 MUM) cells.
      Hepatocellular toxicity of FKB is mediated by induction of oxidative stress,
      depletion of reduced glutathione (GSH), inhibition of IKK activity leading to NF
      kappaB transcriptional blockade, and constitutive TNF-alpha-independent
      activation of mitogen-activated protein kinase (MAPK) signaling pathways, namely,
      ERK, p38, and JNK. We further demonstrate by noninvasive bioluminescence imaging
      that oral consumption of FKB leads to inhibition of hepatic NF-kappaB
      transcriptional activity in vivo and severe liver damage. Surprisingly,
      replenishment with exogenous GSH normalizes both TNF-alpha-dependent NF-kappaB as
      well as MAPK signaling and rescues hepatocytes from FKB-induced death. Our data
      identify FKB as a potent GSH-sensitive hepatotoxin, levels of which should be
      specifically monitored and controlled in kava-containing herb products.

PMID- 20696858
TI  - SHP-1 in T cells limits the production of CD8 effector cells without impacting
      the formation of long-lived central memory cells.
AB  - During responses against viruses and malignancies, naive CD8 T lymphocytes expand
      to form both short-lived effector cells and a population containing cells with
      the potential to be long-lived and participate in memory responses (memory
      precursor effector cells). The strength of antigenic, costimulatory, and cytokine
      signals during responses impacts the magnitude and type of CD8 populations
      formed. In vitro studies have revealed that the tyrosine phosphatase Src homology
      region 2 domain-containing phosphatase-1 (SHP-1) regulates signal transduction
      from receptors on T cells including the TCR, helping set the activation
      threshold, and therefore may shape responses of mature CD8 T cells in vivo.
      Analysis of CD8 T cells from motheaten mice, which are globally deficient in SHP
      1, proved problematic due to cell-extrinsic effects of SHP-1 deficiency in non-T
      cells on CD8 T cells. Therefore, a conditional knockout of SHP-1 in mature single
      positive T cells was developed to analyze cell-intrinsic consequences of complete
      and partial SHP-1 deficiency on CD8 T cell responses to acute viral infection.
      The results demonstrated that SHP-1 has disparate effects on subpopulations of
      responding cells, limiting the magnitude and quality of primary and secondary
      responses by reducing the number of short-lived effector cells generated without
      affecting the size of the memory precursor effector cell pool that leads to
      formation of long-term memory.

PMID- 20696859
TI  - B7-H3 augments the inflammatory response and is associated with human sepsis.
AB  - B7-H3, a new member of the B7 superfamily, acts as both a T cell costimulator and
      coinhibitor, and thus plays a key role in the regulation of T cell-mediated
      immune responses. However, it is unclear whether B7-H3 is involved in the innate
      immune monocyte/macrophage-mediated inflammatory response. In this paper, we show
      that, although B7-H3 alone failed to stimulate proinflammatory cytokine release
      from murine macrophages, it strongly augmented both LPS- and bacterial
      lipoprotein-induced NF-kappaB activation and inflammatory response. This occurred
      in both a TLR4- and TLR2-dependent manner. Blockage of B7-H3 in vivo attenuated
      LPS-induced proinflammatory cytokine release and endotoxic shock-related
      lethality. Furthermore, we found that patients diagnosed with sepsis, in contrast
      to healthy individuals, exhibited significant levels of raised plasma soluble B7
      H3 (sB7-H3) and that this level correlated with the clinical outcome and levels
      of plasma TNF-alpha and IL-6. In addition, a putative receptor for B7-H3 was
      detected on monocytes and peritoneal macrophages from septic patients but not on
      monocytes from healthy donors. Stimulation of human monocytes with LPS and
      inflammatory cytokines led to a substantial release of sB7-H3. Taken together,
      our data indicate that significantly elevated plasma sB7-H3 in septic patients
      may predict a poor outcome. Furthermore, we demonstrate that B7-H3 functions as a
      costimulator of innate immunity by augmenting proinflammatory cytokine release
      from bacterial cell wall product-stimulated monocytes/macrophages and may
      contribute positively to the development of sepsis.

PMID- 20696860
TI  - TCR-dependent translational control of GATA-3 enhances Th2 differentiation.
AB  - The differentiation of CD4(+) T cells into the Th2 subset is controlled by the
      transcription factor GATA-3. GATA-3 is both necessary and sufficient for Th2
      differentiation and works through the induction of chromatin remodeling at the
      Th2 effector cytokine loci. We show in this study that IL-4 stimulation induces
      GATA-3 mRNA upregulation, but the level of GATA-3 protein induced is insufficient
      for Th2 differentiation. The levels of GATA-3 protein and Th2 differentiation are
      enhanced by concomitant TCR signaling through the PI3K/mammalian target of
      rapamycin pathway. The PI3K-mediated increase in GATA-3 protein occurs without
      increasing the GATA-3 mRNA level. Rather, TCR signaling through PI3K specifically
      enhances the translation rate of GATA-3 without affecting the protein stability.
      Importantly, this role of TCR signaling is independent of the effects of TCR
      signaling in T cell survival and expansion. Thus, TCR signaling through PI3K may
      play a critical role in Th2 differentiation by the specific enhancement of GATA-3
      translation.

PMID- 20696861
TI  - Maternal MHC regulates generation of pathogenic antibodies and fetal MHC-encoded
      genes determine susceptibility in congenital heart block.
AB  - Congenital heart block develops in fetuses of anti-Ro52 Ab-positive women. A
      recurrence rate of 20%, despite the persistence of maternal autoantibodies,
      indicates that there are additional, yet unidentified, factors critical for
      development of congenital heart block. In this study, we demonstrate that besides
      the maternal MHC controlling Ab specificity, fetal MHC-encoded genes influence
      fetal susceptibility to congenital heart block. Using MHC congenic rat strains,
      we show that heart block develops in rat pups of three strains carrying MHC
      haplotype RT1(av1) (DA, PVG.AV1, and LEW.AV1) after maternal Ro52 immunization,
      but not in LEW rats (RT1(l)). Different anti-Ro52 Ab fine specificities were
      generated in RT1(av1) versus RT1(l) animals. Maternal and fetal influence was
      determined in an F(2) cross between LEW.AV1 and LEW strains, which revealed
      higher susceptibility in RT1(l) than RT1(av1) pups once pathogenic Ro52 Abs were
      present. This was further confirmed in that RT1(l) pups more frequently developed
      heart block than RT1(av1) pups after passive transfer of RT1(av1) anti-Ro52 sera.
      Our findings show that generation of pathogenic Ro52 Abs is restricted by
      maternal MHC, whereas the fetal MHC locus regulates susceptibility and determines
      the fetal disease outcome in anti-Ro52-positive pregnancies.

PMID- 20696862
TI  - A synthetic peptide vaccine directed against the 2beta2-2beta3 loop of domain 2
      of protective antigen protects rabbits from inhalation anthrax.
AB  - The current vaccines for anthrax in the United States and United Kingdom are
      efficacious in the two most accepted animal models of inhalation anthrax,
      nonhuman primates and rabbits, but require extensive immunization protocols. We
      previously demonstrated that a linear determinant in domain 2 of Bacillus
      anthracis protective Ag (PA) is a potentially important target for an epitope
      specific vaccine for anthrax, as Abs specific for this site, referred to as the
      loop-neutralizing determinant (LND), neutralize lethal toxin in vitro, yet are
      virtually absent in PA-immunized rabbits. In this study, we evaluated the
      immunogenicity and protective efficacy in rabbits of multiple antigenic peptides
      (MAPs) consisting of aa 304-319 from the LND of PA colinearly synthesized at the
      C terminus (T-B MAP) or N terminus (B-T MAP) with a heterologous T cell epitope
      from Plasmodium falciparum. Immunogenicity studies demonstrated that both MAPs
      elicited toxin-neutralizing Ab in rabbits. To evaluate the MAPs as potential
      anthrax vaccines, we immunized groups of rabbits (n = 7) with each MAP in
      Freund's adjuvant and then exposed all rabbits to a 200-LD(50) challenge with
      aerosolized spores of B. anthracis Ames strain. All seven rabbits immunized with
      the B-T MAP and 89% (six of seven) of rabbits immunized with the T-B MAP survived
      the spore challenge. Corollary studies with reference sera from human vaccinees
      immunized with rPA or anthrax vaccine absorbed and nonhuman primates immunized
      with PA revealed no detectable Ab with specificity for the LND. We conclude that
      a synthetic peptide vaccine targeting the LND would be a potentially efficacious
      vaccine for anthrax.

PMID- 20696863
TI  - Separate roles for antigen recognition and lymph node inflammation in CD8+ memory
      T cell formation.
AB  - Priming of naive CD8(+) T cells by pathogens or vaccines generally involves their
      interaction with Ag-loaded dendritic cells (DCs) in the context of an inflamed
      lymph node. Lymph node activation fosters DC and T cell encounters and
      subsequently provides newly primed T cells with nurturing conditions. We
      dissected these two aspects by infusing in vitro primed CD8(+) T cells into naive
      recipient mice harboring a single activated lymph node and comparing the fate of
      these T cells with those infused into control recipients. Brief (20 h) in vitro
      priming empowered the T cells to expand in vivo without further Ag stimulation.
      This primary response was not affected by the presence or absence of a
      nonspecifically activated lymph node. In contrast, in vivo antigenic challenge
      after contraction of the primary response resulted in significantly stronger
      secondary T cell responses in mice harboring activated lymph nodes, demonstrating
      that the availability of an activated lymph node supported the generation of T
      cell memory in an Ag-unrelated manner. The presence of an activated lymph node
      during the expansion and contraction phase of the primary response did not endow
      T cells with an instructional program for increased survival or secondary
      expansion, but primarily served to conserve increased numbers of T cells.

PMID- 20696864
TI  - Gene-specific repression of proinflammatory cytokines in stimulated human
      macrophages by nuclear IkappaBalpha.
AB  - We have previously shown that increased nuclear accumulation of IkappaBalpha
      inhibits NF-kappaB activity and induces apoptosis in human leukocytes. In this
      study, we wanted to explore the possibility that the nucleocytoplasmic
      distribution of IkappaBalpha can be used as a therapeutic target for the
      regulation of NF-kappaB-dependent cytokine synthesis. Treatment of LPS-stimulated
      human U937 macrophages with an inhibitor of chromosome region maintenance 1
      dependent nuclear export, leptomycin B, resulted in the increased nuclear
      accumulation of IkappaBalpha and inhibition of NF-kappaB DNA binding activity,
      caused by the nuclear IkappaBalpha-p65 NF-kappaB interaction. Surprisingly,
      however, whereas mRNA expression and cellular release of TNF-alpha, the beta form
      of pro-IL-1 (IL-1beta), and IL-6 were inhibited by the leptomycin B-induced
      nuclear IkappaBalpha, IL-8 mRNA expression and cellular release were not
      significantly affected. Analysis of in vivo recruitment of p65 NF-kappaB to NF
      kappaB-regulated promoters by chromatin immunoprecipitation in U937 cells and
      human PBMCs indicated that although the p65 recruitment to TNF-alpha, IL-1beta,
      and IL-6 promoters was inhibited by the nuclear IkappaBalpha, p65 recruitment to
      IL-8 promoter was not repressed. Chromatin immunoprecipitation analyses using
      IkappaBalpha and S536 phosphospecific p65 NF-kappaB Abs demonstrated that
      although the newly synthesized IkappaBalpha induced by postinduction repression
      is recruited to TNF-alpha, IL-1beta, and IL-6 promoters but not to the IL-8
      promoter, S536-phosphorylated p65 is recruited to IL-8 promoter, but not to TNF
      alpha, IL-1beta, or IL-6 promoters. Together, these data indicate that the
      inhibition of NF-kappaB-dependent transcription by nuclear IkappaBalpha in LPS
      stimulated macrophages is gene specific and depends on the S536 phosphorylation
      status of the recruited p65 NF-kappaB.

PMID- 20696865
TI  - Quality-of-life measures in children and adults with type 1 diabetes: Juvenile
      Diabetes Research Foundation Continuous Glucose Monitoring randomized trial.
AB  - OBJECTIVE: To evaluate the impact of continuous glucose monitoring (CGM) on
      quality of life (QOL) among individuals with type 1 diabetes. RESEARCH DESIGN AND
      METHODS: In a multicenter trial, 451 children and adults with type 1 diabetes
      were randomly assigned to CGM treatment or the control group. Generic and
      diabetes-specific QOL questionnaires were completed at baseline and 26 weeks by
      all participants and parents of participants <18 years old, and the CGM
      satisfaction scale was completed by the CGM group (participants and parents) at
      26 weeks. RESULTS: After 26 weeks, QOL scores remained largely unchanged for both
      the treatment and the control group, although there was a slight difference
      favoring the adult CGM group on several subscales (P < 0.05). There was
      substantial satisfaction with CGM technology after 26 weeks among participants
      and parents. CONCLUSIONS: Baseline QOL was high, and the measures showed little
      change with CGM use, although a high level of CGM satisfaction was reported.

PMID- 20696866
TI  - Novel radioiodinated {gamma}-hydroxybutyric acid analogues for radiolabeling and
      Photolinking of high-affinity {gamma}-hydroxybutyric acid binding sites.
AB  - gamma-Hydroxybutyric acid (GHB) is a therapeutic drug, a drug of abuse, and an
      endogenous substance that binds to low- and high-affinity sites in the mammalian
      brain. To target the specific GHB binding sites, we have developed a (125)I
      labeled GHB analog and characterized its binding in rat brain homogenate and
      slices. Our data show that [(125)I]4-hydroxy-4-[4-(2
      iodobenzyloxy)phenyl]butanoate ([(125)I]BnOPh-GHB) binds to one site in rat brain
      cortical membranes with low nanomolar affinity (K(d), 7 nM; B(max), 61 pmol/mg
      protein). The binding is inhibited by GHB and selected analogs, but not by gamma
      aminobutyric acid. Autoradiography using horizontal slices from rat brain
      demonstrates the highest density of binding in hippocampus and cortical regions
      and the lowest density in the cerebellum. Altogether, the findings correlate with
      the labeling and brain regional distribution of high-affinity GHB sites or
      [(3)H](E,RS)-(6,7,8,9-tetrahydro-5-hydroxy-5H-benzocyclohept-6-ylidene)acetic
      acid ([(3)H]NCS-382) binding sites. Using a (125)I-labeled photoaffinity
      derivative of the new GHB ligand, we have performed denaturing protein
      electrophoresis and detected one major protein band with an apparent mass of 50
      kDa from cortical and hippocampal membranes. [(125)I]BnOPh-GHB is the first
      reported (125)I-labeled GHB radioligand and is a useful tool for in vitro studies
      of the specific high-affinity GHB binding sites. The related photoaffinity linker
      [(125)I]4-hydroxy-4-[4-(2-azido-5-iodobenzyloxy)phenyl]butanoate can be used as a
      probe for isolation of the elusive GHB binding protein.

PMID- 20696867
TI  - The development of ciprofloxacin resistance in Pseudomonas aeruginosa involves
      multiple response stages and multiple proteins.
AB  - Microbes have developed resistance to nearly every antibiotic, yet the steps
      leading to drug resistance remain unclear. Here we report a multistage process by
      which Pseudomonas aeruginosa acquires drug resistance following exposure to
      ciprofloxacin at levels ranging from 0.5* to 8* the initial MIC. In stage I,
      susceptible cells are killed en masse by the exposure. In stage II, a small, slow
      to nongrowing population survives antibiotic exposure that does not exhibit
      significantly increased resistance according to the MIC measure. In stage III,
      exhibited at 0.5* to 4* the MIC, a growing population emerges to reconstitute the
      population, and these cells display heritable increases in drug resistance of up
      to 50 times the original level. We studied the stage III cells by proteomic
      methods to uncover differences in the regulatory pathways that are involved in
      this phenotype, revealing upregulation of phosphorylation on two proteins,
      succinate-semialdehyde dehydrogenase (SSADH) and methylmalonate-semialdehyde
      dehydrogenase (MMSADH), and also revealing upregulation of a highly conserved
      protein of unknown function. Transposon disruption in the encoding genes for each
      of these targets substantially dampened the ability of cells to develop the stage
      III phenotype. Considering these results in combination with computational models
      of resistance and genomic sequencing results, we postulate that stage III
      heritable resistance develops from a combination of both genomic mutations and
      modulation of one or more preexisting cellular pathways.

PMID- 20696868
TI  - Sodium nitrite-mediated killing of the major cystic fibrosis pathogens
      Pseudomonas aeruginosa, Staphylococcus aureus, and Burkholderia cepacia under
      anaerobic planktonic and biofilm conditions.
AB  - A hallmark of airways in patients with cystic fibrosis (CF) is highly refractory,
      chronic infections by several opportunistic bacterial pathogens. A recent study
      demonstrated that acidified sodium nitrite (A-NO(2)(-)) killed the highly
      refractory mucoid form of Pseudomonas aeruginosa, a pathogen that significantly
      compromises lung function in CF patients (S. S. Yoon et al., J. Clin. Invest.
      116:436-446, 2006). Therefore, the microbicidal activity of A-NO(2)(-) (pH 6.5)
      against the following three major CF pathogens was assessed: P. aeruginosa (a
      mucoid, mucA22 mutant and a sequenced nonmucoid strain, PAO1), Staphylococcus
      aureus USA300 (methicillin resistant), and Burkholderia cepacia, a notoriously
      antibiotic-resistant organism. Under planktonic, anaerobic conditions, growth of
      all strains except for P. aeruginosa PAO1 was inhibited by 7.24 mM (512 MUg ml(
      1) NO(2)(-)). B. cepacia was particularly sensitive to low concentrations of A
      NO(2)(-) (1.81 mM) under planktonic conditions. In antibiotic-resistant
      communities known as biofilms, which are reminiscent of end-stage CF airway
      disease, A-NO(2)(-) killed mucoid P. aeruginosa, S. aureus, and B. cepacia; 1 to
      2 logs of cells were killed after a 2-day incubation with a single dose of ~15 mM
      A-NO(2)(-). Animal toxicology and phase I human trials indicate that these
      bactericidal levels of A-NO(2)(-) can be easily attained by aerosolization. Thus,
      in summary, we demonstrate that A-NO(2)(-) is very effective at killing these
      important CF pathogens and could be effective in other infectious settings,
      particularly under anaerobic conditions where bacterial defenses against the
      reduction product of A-NO(2)(-), nitric oxide (NO), are dramatically reduced.

PMID- 20696869
TI  - Mutations in 23S rRNA at the peptidyl transferase center and their relationship
      to linezolid binding and cross-resistance.
AB  - The oxazolidinone antibiotic linezolid targets the peptidyl transferase center
      (PTC) on the bacterial ribosome. Thirteen single and four double 23S rRNA
      mutations were introduced into a Mycobacterium smegmatis strain with a single
      rRNA operon. Converting bacterial base identity by single mutations at positions
      2032, 2453, and 2499 to human cytosolic base identity did not confer
      significantly reduced susceptibility to linezolid. The largest decrease in
      linezolid susceptibility for any of the introduced single mutations was observed
      with the G2576U mutation at a position that is 7.9 A from linezolid. Smaller
      decreases were observed with the A2503G, U2504G, and G2505A mutations at
      nucleotides proximal to linezolid, showing that the degree of resistance
      conferred is not simply inversely proportional to the nucleotide-drug distance.
      The double mutations G2032A-C2499A, G2032A-U2504G, C2055A-U2504G, and C2055A
      A2572U had remarkable synergistic effects on linezolid resistance relative to the
      effects of the corresponding single mutations. This study emphasizes that effects
      of rRNA mutations at the PTC are organism dependent. Moreover, the data show a
      nonpredictable cross-resistance pattern between linezolid, chloramphenicol,
      clindamycin, and valnemulin. The data underscore the significance of mutations at
      distal nucleotides, either alone or in combination with other mutated
      nucleotides, in contributing to linezolid resistance.

PMID- 20696870
TI  - Discovery and analysis of 4H-pyridopyrimidines, a class of selective bacterial
      protein synthesis inhibitors.
AB  - Bacterial protein synthesis is the target for numerous natural and synthetic
      antibacterial agents. We have developed a poly(U) mRNA-directed
      aminoacylation/translation protein synthesis system composed of phenyl-tRNA
      synthetases, ribosomes, and ribosomal factors from Escherichia coli. This system,
      utilizing purified components, has been used for high-throughput screening of a
      small-molecule chemical library. We have identified a series of compounds that
      inhibit protein synthesis with 50% inhibitory concentrations (IC(50)s) ranging
      from 3 to 14 MUM. This series of compounds all contained the same central
      scaffold composed of tetrahydropyrido[4,3-d]pyrimidin-4-ol (e.g., 4H
      pyridopyrimidine). All analogs contained an ortho pyridine ring attached to the
      central scaffold in the 2 position and either a five- or a six-member ring
      tethered to the 6-methylene nitrogen atom of the central scaffold. These
      compounds inhibited the growth of E. coli, Staphylococcus aureus, Streptococcus
      pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis, with MICs ranging
      from 0.25 to 32 MUg/ml. Macromolecular synthesis (MMS) assays with E. coli and S.
      aureus confirmed that antibacterial activity resulted from specific inhibition of
      protein synthesis. Assays were developed for the steps performed by each
      component of the system in order to ascertain the target of the compounds, and
      the ribosome was found to be the site of inhibition.

PMID- 20696871
TI  - Overexpression of the adeB gene in clinical isolates of tigecycline
      nonsusceptible Acinetobacter baumannii without insertion mutations in adeRS.
AB  - Thirteen clinical isolates of multidrug-resistant Acinetobacter baumannii
      resistant to carbapenems (MRAB-C) with tigecycline nonsusceptibility were
      collected from individual patients in this study. None of the 13 isolates shared
      the same strain characteristics in molecular typing. All of them showed increased
      adeB transcription, as predicted. However, none of these tigecycline
      nonsusceptible MRAB-C isolates were found to possess previously known adeRS
      mutations. Upregulation of adeB transcription may result from cross stimulation
      by other mechanisms.

PMID- 20696872
TI  - Affinity of ceftobiprole for penicillin-binding protein 2b in Streptococcus
      pneumoniae strains with various susceptibilities to penicillin.
AB  - Wild-type penicillin-binding protein (PBP) 2b from penicillin-susceptible
      Streptococcus pneumoniae had high affinity for ceftobiprole and penicillin (50%
      inhibitory concentrations [IC(50)s] of <=0.15 MUg/ml) but not ceftriaxone (IC(50)
      of >8 MUg/ml). In clinical isolates, ceftobiprole and PBP 2b affinities were
      reduced 15- to 30-fold with a Thr-446-Ala substitution and further still with an
      additional Ala-619-Gly PBP 2b substitution. Ceftobiprole remained active (MICs of
      <=1 MUg/ml) against all strains tested and behaved more like penicillin than
      ceftriaxone with respect to PBP 2b binding.

PMID- 20696873
TI  - Comparative biochemical and computational study of the role of naturally
      occurring mutations at Ambler positions 104 and 170 in GES beta-lactamases.
AB  - In GES-type beta-lactamases, positions 104 and 170 are occupied by Glu or Lys and
      by Gly, Asn, or Ser, respectively. Previous studies have indicated an important
      role of these amino acids in the interaction with beta-lactams, although their
      precise role, especially that of residue 104, remains uncertain. In this study,
      we constructed GES-1 (Glu104, Gly170), GES-2 (Glu104, Asn170), GES-5 (Glu104,
      Ser170), GES-6 (Lys104, Ser170), GES-7 (Lys104, Gly170), and GES-13 (Lys104,
      Asn170) by site-specific mutagenesis and compared their hydrolytic properties.
      Isogenic comparisons of beta-lactam resistance levels conferred by these GES
      variants were also performed. Data indicated the following patterns: (i) Lys104
      containing enzymes exhibited enhanced hydrolysis of oxyimino-cephalosporins and
      reduced efficiency against imipenem in relation to enzymes possessing Glu104,
      (ii) Asn170-containing enzymes showed reduced hydrolysis rates of penicillins and
      older cephalosporins, (iii) Ser170 enabled GES to hydrolyze cefoxitin
      efficiently, and (iv) Asn170 and Ser170 increased the carbapenemase character of
      GES enzymes but reduced their activity against ceftazidime. Molecular dynamic
      simulations of GES apoenzyme models, as well as construction of GES structures
      complexed with cefoxitin and an achiral ceftazidime-like boronic acid, provided
      insights into the catalytic behavior of the studied mutants. There were
      indications that an increased stability of the hydrogen bonding network of Glu166
      Lys73-Ser70 and an altered positioning of Trp105 correlated with the substrate
      spectra, especially with acylation of GES by imipenem. Furthermore, likely
      effects of Ser170 on GES interactions with cefoxitin and of Lys104 on
      interactions with oxyimino-cephalosporins were revealed. Overall, the data
      unveiled the importance of residues 104 and 170 in the function of GES enzymes.

PMID- 20696874
TI  - High-resolution crystal structure of the subclass B3 metallo-beta-lactamase BJP
      1: rational basis for substrate specificity and interaction with sulfonamides.
AB  - Metallo-beta-lactamases (MBLs) are important enzymatic factors in resistance to
      beta-lactam antibiotics that show important structural and functional
      heterogeneity. BJP-1 is a subclass B3 MBL determinant produced by Bradyrhizobium
      japonicum that exhibits interesting properties. BJP-1, like CAU-1 of Caulobacter
      vibrioides, overall poorly recognizes beta-lactam substrates and shows an unusual
      substrate profile compared to other MBLs. In order to understand the structural
      basis of these properties, the crystal structure of BJP-1 was obtained at 1.4-A
      resolution. This revealed significant differences in the conformation and
      locations of the active-site loops, determining a rather narrow active site and
      the presence of a unique N-terminal helix bearing Phe-31, whose side chain binds
      in the active site and represents an obstacle for beta-lactam substrate binding.
      In order to probe the potential of sulfonamides (known to inhibit various zinc
      dependent enzymes) to bind in the active sites of MBLs, the structure of BJP-1 in
      complex with 4-nitrobenzenesulfonamide was also obtained (at 1.33-A resolution),
      thereby revealing the mode of interaction of these molecules in MBLs.
      Interestingly, sulfonamide binding resulted in the displacement of the side chain
      of Phe-31 from its hydrophobic binding pocket, where the benzene ring of the
      molecule is now found. These data further highlight the structural diversity
      shown by MBLs but also provide interesting insights in the structure-function
      relationships of these enzymes. More importantly, we provided the first
      structural observation of MBL interaction with sulfonamides, which might
      represent an interesting scaffold for the design of MBL inhibitors.

PMID- 20696875
TI  - Complete nucleotide sequence of KPC-3-encoding plasmid pKpQIL in the epidemic
      Klebsiella pneumoniae sequence type 258.
AB  - We have determined the entire DNA sequence of plasmid pKpQIL, the bla(KPC-3)
      carrying plasmid harbored by the carbapenem-resistant Klebsiella pneumoniae clone
      sequence type 258 (ST 258) in Israel. pKpQIL is a 113,637-bp, self-transmissible
      plasmid that belongs to the incompatibility group IncFII. It consists of a large
      backbone of a pKPN4-like plasmid and carries the bla(KPC-3)-containing Tn4401a
      transposon of a pNYC-like plasmid.

PMID- 20696876
TI  - Prevalence and dissemination of oqxAB in Escherichia coli isolates from animals,
      farmworkers, and the environment.
AB  - OqxAB has recently been identified as one of the mechanisms of plasmid-mediated
      quinolone resistance (PMQR). Compared to what is observed for other PMQR
      determinants, there is a paucity of data with regard to the prevalence and
      epidemiology of OqxAB and its contribution to resistance to different
      antimicrobials. In this study, the prevalence and dissemination of oqxAB and
      other PMQR genes in Escherichia coli isolates from animals, farmworkers, and the
      environment in 2002 in China were investigated. Of the 172 E. coli isolates,
      39.0% carried oqxA, while only 4.1%, 2.9%, and 0.6% carried qnr (1 qnrB6 isolate,
      5 qnrS1 isolates, and 1 qnrD isolate), qepA, and aac(6')-Ib-cr, respectively.
      Among the 33 isolates from farmworkers, 10 (30.3%) were positive for oqxA. oqxAB
      was associated with IS26 and was carried on the 43- to 115-kb IncF transferable
      plasmid. Transconjugants carrying oqxAB showed 4- to 16-fold increases in the
      MICs of quinolones, 16- to 64-fold increases in the MICs of quinoxalines, 8- to
      32-fold increases in the MICs of chloramphenicol and trimethoprim
      sulfamethoxazole, and 4- to 8-fold increases in the MICs of florfenicol compared
      to the levels for the recipient. The pulsed-field gel electrophoresis (PFGE)
      analysis showed that the high levels of prevalence and dissemination of oqxAB in
      E. coli in animal farms were primarily due to the transmission of plasmids
      carrying oqxAB, although clonal transmission between human and swine E. coli
      isolates was observed. It is concluded that oqxAB was widespread in animal farms
      in China, which may be due to the overuse of quinoxalines in animals. This study
      warrants the prudent use of quinoxalines in food animals.

PMID- 20696877
TI  - Cationic amphiphiles, a new generation of antimicrobials inspired by the natural
      antimicrobial peptide scaffold.
AB  - Naturally occurring cationic antimicrobial peptides (AMPs) and their mimics form
      a diverse class of antibacterial agents currently validated in preclinical and
      clinical settings for the treatment of infections caused by antimicrobial
      resistant bacteria. Numerous studies with linear, cyclic, and diastereomeric AMPs
      have strongly supported the hypothesis that their physicochemical properties,
      rather than any specific amino acid sequence, are responsible for their
      microbiological activities. It is generally believed that the amphiphilic
      topology is essential for insertion into and disruption of the cytoplasmic
      membrane. In particular, the ability to rapidly kill bacteria and the relative
      difficulty with which bacteria develop resistance make AMPs and their mimics
      attractive targets for drug development. However, the therapeutic use of
      naturally occurring AMPs is hampered by the high manufacturing costs, poor
      pharmacokinetic properties, and low bacteriological efficacy in animal models. In
      order to overcome these problems, a variety of novel and structurally diverse
      cationic amphiphiles that mimic the amphiphilic topology of AMPs have recently
      appeared. Many of these compounds exhibit superior pharmacokinetic properties and
      reduced in vitro toxicity while retaining potent antibacterial activity against
      resistant and nonresistant bacteria. In summary, cationic amphiphiles promise to
      provide a new and rich source of diverse antibacterial lead structures in the
      years to come.

PMID- 20696878
TI  - Efficacy of the combination of tobramycin and a macrolide in an in vitro
      Pseudomonas aeruginosa mature biofilm model.
AB  - Respiratory disease is the main cause of morbidity and mortality in patients with
      cystic fibrosis (CF). In particular, patients suffer from chronic infection due
      to biofilm formation by opportunistic Pseudomonas aeruginosa (32). Therefore,
      there is an urgent need to develop alternative ways to treat biofilm-associated
      clinical infections. The aim of this study was to compare the antimicrobial
      effects in vitro of the combinations tobramycin-clarithromycin and tobramycin
      azithromycin against five P. aeruginosa biofilms and to establish the most
      effective combination. We performed a kinetic study over a period of 28 days of a
      twice-daily coadministration of the combinations tobramycin-clarithromycin and
      tobramycin-azithromycin on 12-day-old, mature P. aeruginosa biofilms formed on
      microplate pegs for 4 clinical isolates and one laboratory strain (PAO1) to
      simulate the treatment of CF patients with tobramycin inhalation solution (TOBI)
      through aerosolization. A synergy between tobramycin and clarithromycin was
      recorded for 3/5 biofilms, with a bacterial decrease of more than 5 log.
      Conversely, we found an antagonistic activity when 4 MUg/ml tobramycin was
      administered with azithromycin at 2 MUg/ml for P. aeruginosa PAO1 and with
      azithromycin at 2, 20, 50, 100, and 200 MUg/ml for P. aeruginosa PYO1. Treatment
      with tobramycin at 4 MUg/ml combined with clarithromycin at 200 MUg/ml eradicated
      all five biofilms, while tobramycin-azithromycin at the same concentrations
      eradicated only three biofilms. Results of this study suggest that local
      administration of tobramycin and clarithromycin into the respiratory tract
      represents a better strategy than the combination tobramycin-azithromycin for the
      treatment of P. aeruginosa-associated pulmonary infections.

PMID- 20696879
TI  - Overexpression of resistance-nodulation-cell division pump AdeFGH confers
      multidrug resistance in Acinetobacter baumannii.
AB  - Acinetobacter baumannii is a major nosocomial pathogen which frequently develops
      multidrug resistance by acquisition of antibiotic resistance genes and
      overexpression of intrinsic efflux systems, such as the RND efflux pumps AdeABC
      and AdeIJK. A third RND system was characterized by studying spontaneous mutants
      BM4663 and BM4664, which were selected in the presence of chloramphenicol and
      norfloxacin, respectively, from the AdeABC- and AdeIJK-defective derivative A.
      baumannii BM4652. They exhibited enhanced resistance to fluoroquinolones,
      tetracycline-tigecycline, chloramphenicol, clindamycin, trimethoprim,
      sulfamethoxazole, sodium dodecyl sulfate, and dyes such as ethidium bromide,
      safranin O, and acridine orange. Comparison of transcriptomes of mutants with
      that of their parental strain, using a microarray technology, demonstrated the
      overexpression of three genes that encoded an RND efflux system, named AdeFGH.
      Inactivation of AdeFGH in BM4664 restored an antibiotic susceptibility profile
      identical to that of BM4652, indicating that AdeFGH was cryptic in BM4652 and
      responsible for multidrug resistance in its mutants. RNA analysis demonstrated
      that the three genes were cotranscribed. The adeFGH operon was found in 36 out of
      40 A. baumannii clinical isolates, but none of the 22 isolates tested
      overexpressed the pump genes. Spontaneous MDR mutant BM4684, overexpressing
      adeFGH, was obtained from clinical isolate BM4587, indicating that adeFGH can be
      overexpressed in a strain harboring adeABC-adeIJK. An open reading frame, coding
      a LysR-type transcriptional regulator, named adeL, was located upstream from the
      adeFGH operon and transcribed in the opposite direction. Mutations in adeL were
      found in the three adeFGH-overexpressing mutants, suggesting that they were
      responsible for overexpression of AdeFGH.

PMID- 20696880
TI  - Activities of high-dose daptomycin, vancomycin, and moxifloxacin alone or in
      combination with clarithromycin or rifampin in a novel in vitro model of
      Staphylococcus aureus biofilm.
AB  - Biofilm formation is an important virulence factor that allows bacteria to resist
      host responses and antibacterial agents. The aim of the study was to assess the
      in vitro activities of several antimicrobials alone or in combination against two
      Staphylococcus aureus isolates in a novel pharmacokinetic/pharmacodynamic (PK/PD)
      model of biofilm for 3 days. One methicillin-susceptible S. aureus strain
      (SH1000) and one methicillin-resistant S. aureus strain (N315) were evaluated in
      a modified biofilm reactor with polystyrene coupons. Simulated regimens included
      vancomycin (VAN) plus rifampin (RIF), moxifloxacin (MOX), and high doses (10
      mg/kg of body weight/day) of daptomycin (DAP) alone or combined with RIF or
      clarithromycin (CLA). Against viable planktonic bacteria (PB) and biofilm
      embedded bacteria (BB) of SH1000, neither DAP nor MOX alone was bactericidal. In
      contrast, the combination of DAP or MOX with CLA significantly increased the
      activity of the two agents against both PB and BB (P < 0.01), and DAP plus CLA
      reached the limit of detection at 72 h. Against PB of N315, DAP alone briefly
      achieved bactericidal activity at 24 h, whereas sustained bactericidal activity
      was observed at 32 h with VAN plus RIF. Overall, only a minimal reduction was
      observed with both regimens against BB (<2.8 log(10) CFU/ml). Finally, the
      combination of DAP and RIF was bactericidal against both PB and BB, achieving the
      limit of detection at 72 h. In conclusion, we developed a novel in vitro PK/PD
      model to assess the activities of antimicrobials against mature bacterial
      biofilm. Combinations of DAP or MOX with CLA were the most effective regimens and
      may represent promising options to treat persistent infections caused by S.
      aureus biofilms.

PMID- 20696881
TI  - Maternal-fetal pharmacokinetics and dynamics of a single intrapartum dose of
      maraviroc in rhesus macaques.
AB  - Single-dose nevirapine (NVP) is effective in reducing mother-to-child
      transmission (MTCT) of HIV; however, the subsequent development of drug
      resistance is problematic. The pharmacokinetic profile of the HIV entry inhibitor
      maraviroc after a single intrapartum dose in rhesus macaques was studied to
      determine whether maraviroc could serve as an alternative to NVP in a single-dose
      strategy. Four pregnant macaques received an oral dose of maraviroc 2 h before
      delivery, and both infant and maternal plasma maraviroc concentrations and CCR5
      receptor occupancy on CD4(+) lymphocytes were measured over time. Maximum plasma
      maraviroc concentrations were found at delivery (2-h-postintrapartum dose) in
      both the mothers and infants, with median concentrations of 974 ng/ml (range, 86
      to 2,830 ng/ml) and 22 ng/ml (range, 4 to 99 ng/ml), respectively. Maraviroc was
      detected in the plasma of mothers up to 48 h after dosing but only as long as 3.5
      h in the infants. The median fetal-maternal area under the concentration-time
      curve (AUC) ratio was 0.009 (range, 0.000 to 0.015). Maraviroc receptor occupancy
      data showed evidence of unprotected CCR5 receptors on CD4(+) cells in the mothers
      24 to 48 h after dosing. Extremely low CCR5 expression on CD4(+) cells of newborn
      macaques prevented determination of receptor occupancy in the infants. In rhesus
      macaques, maraviroc was poorly transferred across the placenta and was quickly
      cleared from the infants' blood. The low concentrations of fetal maraviroc and
      short pharmacokinetic profile in infants suggest that a single maternal
      intrapartum dose of maraviroc would not be effective in reducing the risk of MTCT
      of HIV.

PMID- 20696882
TI  - Population pharmacokinetic-pharmacogenetic study of nevirapine in HIV-infected
      Cambodian patients.
AB  - The aims of this ANRS12154 open-label, single-center, multiple-dose
      pharmacokinetic study were to characterize nevirapine pharmacokinetics in a
      Cambodian population of HIV-infected patients and to identify environmental and
      genetic factors of variability, focusing on the CYP2B6, CYP3A5, and ABCB1 (MDR1)
      genes. A total of 170 Cambodian HIV-infected patients were included. Nevirapine
      trough concentrations were measured after 18 and 36 months of starting
      antiretroviral treatment and in samples drawn during a dosing interval in a
      subset of 10 patients. All data were analyzed by nonlinear mixed-effects
      modeling. The effect of covariates was investigated using the population
      pharmacokinetic model. Patients carrying homozygous loss-of-function alleles
      CYP3A5 6986A>G, CYP2B6 516G>T, CYP2B6 1459C>T, and ABCB1 3435C>T represent 42.4%,
      9.2%, 0%, and 18% of the population, respectively. The median nevirapine trough
      concentrations did not differ after 18 and 36 months of treatment (5,705 ng/ml
      [range, <=50 to 13,871] and 5,709 ng/ml [range, <=50 to 15,422], respectively).
      Interpatient and intrapatient variabilities of nevirapine apparent clearance were
      28% and 17%, respectively. CYP2B6 516G>T and creatinine clearance were found to
      significantly affect nevirapine apparent clearance. The estimated nevirapine
      apparent clearances were 2.95 liters/h, 2.62 liters/h, and 1.86 liters/h for
      CYP2B6 516GG, CYP2B6 516GT, and CYP2B6 516TT genotypes, respectively. The impact
      of creatinine clearance was small. This study demonstrates that 95% of the
      patients had sustained nevirapine exposure well above the 3,000-ng/ml threshold.
      Nevirapine clearance was shown to be affected by CYP2B6 516G>T genetic
      polymorphism and creatinine clearance, although this explained only part of the
      interpatient variability, which remains low compared to that for other
      antiretroviral drugs.

PMID- 20696883
TI  - Challenges of capacity building in multisector community health alliances.
AB  - Capacity building is often described as fundamental to the success of health
      alliances, yet there are few evaluations that provide alliances with clear
      guidance on the challenges related to capacity building. This article attempts to
      identify potential challenges of capacity building in multistakeholder health
      alliances. The study uses a multiple case study design to identify potential
      challenges and trade-offs associated with capacity building in four community
      health alliances in the United States. Multiple challenges were found to be
      common across the four alliances, including specifying appropriate governance
      structures and decision-making frameworks, aligning stakeholder interests with
      the vision of the alliance, balancing short-term objectives with long-term goals,
      and securing resources to sustain the effort without compromising it. These
      challenges often involved trade-offs and choices that alliances need to prepare
      for if they are to approach capacity building in a planful rather than a reactive
      manner.

PMID- 20696884
TI  - Facilitators, challenges, and collaborative activities in faith and health
      partnerships to address health disparities.
AB  - Interest in partnering with faith-based organizations (FBOs) to address health
      disparities has grown in recent years. Yet relatively little is known about these
      types of partnerships. As part of an evaluation of the Institute for Faith and
      Public Health Collaborations, representatives of 34 faith-health teams (n = 61)
      completed semi-structured interviews. Interviews were tape recorded, transcribed,
      and coded by two members of the evaluation team to identify themes. Major
      facilitators to faith-health collaborative work were passion and commitment,
      importance of FBOs in communities, favorable political climate, support from
      community and faith leaders, diversity of teams, and mutual trust and respect.
      Barriers unique to faith and health collaboration included discomfort with FBOs,
      distrust of either health agencies or FBOs, diversity within faith communities,
      different agendas, separation of church and state, and the lack of a common
      language. Findings suggest that faith-health partnerships face unique challenges
      but are capable of aligning resources to address health disparities.

PMID- 20696885
TI  - Perennial lifestyle--an adaptation to nutrient limitation?

PMID- 20696886
TI  - Aspartate-glutamate-alanine-histidine box motif (DEAH)/RNA helicase A helicases
      sense microbial DNA in human plasmacytoid dendritic cells.
AB  - Toll-like receptor 9 (TLR9) senses microbial DNA and triggers type I IFN
      responses in plasmacytoid dendritic cells (pDCs). Previous studies suggest the
      presence of myeloid differentiation primary response gene 88 (MyD88)-dependent
      DNA sensors other than TLR9 in pDCs. Using MS, we investigated C-phosphate-G
      (CpG)-binding proteins from human pDCs, pDC-cell lines, and interferon regulatory
      factor 7 (IRF7)-expressing B-cell lines. CpG-A selectively bound the aspartate
      glutamate-any amino acid-aspartate/histidine (DExD/H)-box helicase 36 (DHX36),
      whereas CpG-B selectively bound DExD/H-box helicase 9 (DHX9). Although the
      aspartate-glutamate-alanine-histidine box motif (DEAH) domain of DHX36 was
      essential for CpG-A binding, the domain of unknown function 1605 (DUF1605 domain)
      of DHX9 was required for CpG-B binding. DHX36 is associated with IFN-alpha
      production and IRF7 nuclear translocation in response to CpG-A, but DHX9 is
      important for TNF-alpha and IL-6 production and NF-kappaB activation in response
      to CpG-B. Knocking down DHX9 or DHX36 significantly reduced the cytokine
      responses of pDCs to a DNA virus but had no effect on the cytokine responses to
      an RNA virus. We further showed that both DHX9 and DHX36 are localized within the
      cytosol and are directly bound to the Toll-interleukin receptor domain of MyD88
      via their helicase-associated domain 2 and DUF domains. This study demonstrates
      that DHX9/DHX36 represent the MyD88-dependent DNA sensors in the cytosol of pDCs
      and suggests a much broader role for DHX helicases in viral sensing.

PMID- 20696887
TI  - Filtration of submicrometer particles by pelagic tunicates.
AB  - Salps are common in oceanic waters and have higher per-individual filtration
      rates than any other zooplankton filter feeder. Although salps are centimeters in
      length, feeding via particle capture occurs on a fine, mucous mesh (fiber
      diameter d approximately 0.1 microm) at low velocity (U = 1.6 +/- 0.6 cmxs(-1),
      mean +/- SD) and is thus a low Reynolds-number (Re approximately 10(-3)) process.
      In contrast to the current view that particle encounter is dictated by simple
      sieving of particles larger than the mesh spacing, a low-Re mathematical model of
      encounter rates by the salp feeding apparatus for realistic oceanic particle-size
      distributions shows that submicron particles, due to their higher abundances, are
      encountered at higher rates (particles per time) than larger particles. Data from
      feeding experiments with 0.5-, 1-, and 3-microm diameter polystyrene spheres
      corroborate these findings. Although particles larger than 1 microm (e.g.,
      flagellates, small diatoms) represent a larger carbon pool, smaller particles in
      the 0.1- to 1-microm range (e.g., bacteria, Prochlorococcus) may be more quickly
      digestible because they present more surface area, and we find that particles
      smaller than the mesh size (1.4 microm) can fully satisfy salp energetic needs.
      Furthermore, by packaging submicrometer particles into rapidly sinking fecal
      pellets, pelagic tunicates can substantially change particle-size spectra and
      increase downward fluxes in the ocean.

PMID- 20696888
TI  - Hyperactivation of nuclear factor of activated T cells 1 (NFAT1) in T cells
      attenuates severity of murine autoimmune encephalomyelitis.
AB  - Nuclear factor of activated T cells (NFAT) proteins are a group of Ca(2+)
      regulated transcription factors residing in the cytoplasm of resting cells.
      Dephosphorylation by calcineurin results in nuclear translocation of NFAT and
      subsequent expression of target genes; rephosphorylation by kinases, including
      casein kinase 1 (CK1), restores NFAT to its latent state in the cytoplasm. We
      engineered a hyperactivable version of NFAT1 with increased affinity for
      calcineurin and decreased affinity for casein kinase 1. Mice expressing
      hyperactivable NFAT1 in their T-cell compartment exhibited a dramatically
      increased frequency of both IL-17- and IL-10-producing cells after
      differentiation under Th17 conditions-this was associated with direct binding of
      NFAT1 to distal regulatory regions of Il-17 and Il-10 gene loci in Th17 cells.
      Despite higher IL-17 production in culture, the mice were significantly less
      prone to myelin oligodendrocyte glycoprotein peptide-induced experimental
      autoimmune encephalomyelitis than controls, correlating with increased production
      of the immunomodulatory cytokine IL-10 and enhanced accumulation of regulatory T
      cells within the CNS. Thus, NFAT hyperactivation paradoxically leads to decreased
      susceptibility to experimental autoimmune encephalomyelitis, supporting previous
      observations linking defects in Ca(2+)/NFAT signaling to lymphoproliferation and
      autoimmune disease.

PMID- 20696889
TI  - Oligogenic basis of isolated gonadotropin-releasing hormone deficiency.
AB  - Between the genetic extremes of rare monogenic and common polygenic diseases lie
      diverse oligogenic disorders involving mutations in more than one locus in each
      affected individual. Elucidating the principles of oligogenic inheritance and
      mechanisms of genetic interactions could help unravel the newly appreciated role
      of rare sequence variants in polygenic disorders. With few exceptions, however,
      the precise genetic architecture of oligogenic diseases remains unknown. Isolated
      gonadotropin-releasing hormone (GnRH) deficiency caused by defective secretion or
      action of hypothalamic GnRH is a rare genetic disease that manifests as sexual
      immaturity and infertility. Recent reports of patients who harbor pathogenic rare
      variants in more than one gene have challenged the long-held view that the
      disorder is strictly monogenic, yet the frequency and extent of oligogenicity in
      isolated GnRH deficiency have not been investigated. By systematically defining
      genetic variants in large cohorts of well-phenotyped patients (n = 397), family
      members, and unaffected subjects (n = 179) for the majority of known disease
      genes, this study suggests a significant role of oligogenicity in this disease.
      Remarkably, oligogenicity in isolated GnRH deficiency was as frequent as
      homozygosity/compound heterozygosity at a single locus (2.5%). Among the 22% of
      patients with detectable rare protein-altering variants, the likelihood of
      oligogenicity was 11.3%. No oligogenicity was detected among controls (P < 0.05),
      even though deleterious variants were present. Viewing isolated GnRH deficiency
      as an oligogenic condition has implications for understanding the pathogenesis of
      its reproductive and nonreproductive phenotypes; deciphering the etiology of
      common GnRH-related disorders; and modeling the genetic architecture of other
      oligogenic and multifactorial diseases.

PMID- 20696890
TI  - Entrainment of disrupted circadian behavior through inhibition of casein kinase 1
      (CK1) enzymes.
AB  - Circadian pacemaking requires the orderly synthesis, posttranslational
      modification, and degradation of clock proteins. In mammals, mutations in casein
      kinase 1 (CK1) epsilon or delta can alter the circadian period, but the
      particular functions of the WT isoforms within the pacemaker remain unclear. We
      selectively targeted WT CK1epsilon and CK1delta using pharmacological inhibitors
      (PF-4800567 and PF-670462, respectively) alongside genetic knockout and knockdown
      to reveal that CK1 activity is essential to molecular pacemaking. Moreover,
      CK1delta is the principal regulator of the clock period: pharmacological
      inhibition of CK1delta, but not CK1epsilon, significantly lengthened circadian
      rhythms in locomotor activity in vivo and molecular oscillations in the
      suprachiasmatic nucleus (SCN) and peripheral tissue slices in vitro. Period
      lengthening mediated by CK1delta inhibition was accompanied by nuclear retention
      of PER2 protein both in vitro and in vivo. Furthermore, phase mapping of the
      molecular clockwork in vitro showed that PF-670462 treatment lengthened the
      period in a phase-specific manner, selectively extending the duration of PER2
      mediated transcriptional feedback. These findings suggested that CK1delta
      inhibition might be effective in increasing the amplitude and synchronization of
      disrupted circadian oscillators. This was tested using arrhythmic SCN slices
      derived from Vipr2(-/-) mice, in which PF-670462 treatment transiently restored
      robust circadian rhythms of PER2::Luc bioluminescence. Moreover, in mice rendered
      behaviorally arrhythmic by the Vipr2(-/-) mutation or by constant light, daily
      treatment with PF-670462 elicited robust 24-h activity cycles that persisted
      throughout treatment. Accordingly, selective pharmacological targeting of the
      endogenous circadian regulator CK1delta offers an avenue for therapeutic
      modulation of perturbed circadian behavior.

PMID- 20696891
TI  - Mechanisms of estrogen receptor antagonism toward p53 and its implications in
      breast cancer therapeutic response and stem cell regulation.
AB  - Estrogen receptor alpha (ERalpha) plays an important role in the onset and
      progression of breast cancer, whereas p53 functions as a major tumor suppressor.
      We previously reported that ERalpha binds to p53, resulting in inhibition of
      transcriptional regulation by p53. Here, we report on the molecular mechanisms by
      which ERalpha suppresses p53's transactivation function. Sequential ChIP assays
      demonstrated that ERalpha represses p53-mediated transcriptional activation in
      human breast cancer cells by recruiting nuclear receptor corepressors (NCoR and
      SMRT) and histone deacetylase 1 (HDAC1). RNAi-mediated down-regulation of NCoR
      resulted in increased endogenous expression of the cyclin-dependent kinase (CDK)
      inhibitor p21(Waf1/Cip1) (CDKN1A) gene, a prototypic transcriptional target of
      p53. While 17beta-estradiol (E2) enhanced ERalpha binding to p53 and inhibited
      p21 transcription, antiestrogens decreased ERalpha recruitment and induced
      transcription. The effects of estrogen and antiestrogens on p21 transcription
      were diametrically opposite to their known effects on the conventional ERE
      containing ERalpha target gene, pS2/TFF1. These results suggest that ERalpha uses
      dual strategies to promote abnormal cellular proliferation: enhancing the
      transcription of ERE-containing proproliferative genes and repressing the
      transcription of p53-responsive antiproliferative genes. Importantly, ERalpha
      binds to p53 and inhibits transcriptional activation by p53 in stem/progenitor
      cell-containing murine mammospheres, suggesting a potential role for the ER-p53
      interaction in mammary tissue homeostasis and cancer formation. Furthermore,
      retrospective studies analyzing response to tamoxifen therapy in a subset of
      patients with ER-positive breast cancer expressing either wild-type or mutant p53
      suggest that the presence of wild-type p53 is an important determinant of
      positive therapeutic response.

PMID- 20696892
TI  - Hypothesis-driven structural connectivity analysis supports network over
      hierarchical model of brain architecture.
AB  - The brain is usually described as hierarchically organized, although an
      alternative network model has been proposed. To help distinguish between these
      two fundamentally different structure-function hypotheses, we developed an
      experimental circuit-tracing strategy that can be applied to any starting point
      in the nervous system and then systematically expanded, and applied it to a
      previously obscure dorsomedial corner of the nucleus accumbens identified
      functionally as a "hedonic hot spot." A highly topographically organized set of
      connections involving expected and unexpected gray matter regions was identified
      that prominently features regions associated with appetite, stress, and clinical
      depression. These connections are arranged as a longitudinal series of circuits
      (closed loops). Thus, the results do not support a rigidly hierarchical model of
      nervous system organization but instead indicate a network model of organization.
      In principle, the double-coinjection circuit tracing strategy can be applied
      systematically to the rest of the nervous system to establish the architecture of
      the global structural wiring diagram, and its abstraction, the connectome.

PMID- 20696893
TI  - Roles for the transcription elongation factor NusA in both DNA repair and damage
      tolerance pathways in Escherichia coli.
AB  - We report observations suggesting that the transcription elongation factor NusA
      promotes a previously unrecognized class of transcription-coupled repair (TCR) in
      addition to its previously proposed role in recruiting translesion synthesis
      (TLS) DNA polymerases to gaps encountered during transcription. Earlier, we
      reported that NusA physically and genetically interacts with the TLS DNA
      polymerase DinB (DNA pol IV). We find that Escherichia coli nusA11(ts) mutant
      strains, at the permissive temperature, are highly sensitive to nitrofurazone
      (NFZ) and 4-nitroquinolone-1-oxide but not to UV radiation. Gene expression
      profiling suggests that this sensitivity is unlikely to be due to an indirect
      effect on gene expression affecting a known DNA repair or damage tolerance
      pathway. We demonstrate that an N(2)-furfuryl-dG (N(2)-f-dG) lesion, a structural
      analog of the principal lesion generated by NFZ, blocks transcription by E. coli
      RNA polymerase (RNAP) when present in the transcribed strand, but not when
      present in the nontranscribed strand. Our genetic analysis suggests that NusA
      participates in a nucleotide excision repair (NER)-dependent process to promote
      NFZ resistance. We provide evidence that transcription plays a role in the repair
      of NFZ-induced lesions through the isolation of RNAP mutants that display altered
      ability to survive NFZ exposure. We propose that NusA participates in an
      alternative class of TCR involved in the identification and removal of a class of
      lesion, such as the N(2)-f-dG lesion, which are accurately and efficiently
      bypassed by DinB in addition to recruiting DinB for TLS at gaps encountered by
      RNAP.

PMID- 20696894
TI  - Clustering of dispersed ribosomal DNA and its role in gene regulation and
      chromosome-end associations in malaria parasites.
AB  - Dynamic changes in gene positioning contribute to differential expression of
      virulence-related gene families in protozoan pathogens; however, the role of
      nuclear architecture in gene expression in the human malaria parasite Plasmodium
      falciparum remains poorly understood. Here we investigated the developmentally
      regulated ribosomal RNA (rRNA) gene family in P. falciparum, which, unlike that
      in most eukaryotes, contains only a few unlinked copies of rRNA genes scattered
      over the subtelomeric regions of several chromosomes. We show that active and
      silent members of this gene family cluster in a single perinuclear nucleolus.
      This rDNA nuclear confinement is DNA sequence dependent, as plasmids carrying
      rDNA fragments are targeted to the nucleolus. Likewise, insertion of an rDNA
      sequence into a subtelomere from a chromosome lacking rRNA genes leads to
      repositioning in the nucleolus. Furthermore, we observed that rDNA spatial
      organization restricted interchromosomal interactions, as chromosome end-bearing
      rRNA genes were found to be preferentially juxtaposed, demonstrating nonrandom
      association of telomeres. Using Br-UTP incorporation, we observed two alpha
      amanitin-resistant nucleolar transcription sites that disappeared when the rDNA
      cluster broke up in the replicative blood stages. Taken together, our results
      provide conceptual insights into functionally differentiated nuclear territories
      and their role in gene expression in malaria parasites.

PMID- 20696895
TI  - Coexpression of potato type I and II proteinase inhibitors gives cotton plants
      protection against insect damage in the field.
AB  - Potato type I and II serine protease inhibitors are produced by solanaceous
      plants as a defense mechanism against insects and microbes. Nicotiana alata
      proteinase inhibitor (NaPI) is a multidomain potato type II inhibitor (pin II)
      that is produced at high levels in the female reproductive tissues of the
      ornamental tobacco, Nicotiana alata. The individual inhibitory domains of NaPI
      target the major classes of digestive enzymes, trypsin and chymotrypsin, in the
      gut of lepidopteran larval pests. Although consumption of NaPI dramatically
      reduced the growth and development of a major insect pest, Helicoverpa
      punctigera, we discovered that surviving larvae had high levels of chymotrypsin
      activity resistant to inhibition by NaPI. We found a potato type I inhibitor,
      Solanum tuberosum potato type I inhibitor (StPin1A), was a strong inhibitor of
      the NaPI-resistant chymotrypsin activity. The combined inhibitory effect of NaPI
      and StPin1A on H. armigera larval growth in the laboratory was reflected in the
      increased yield of cotton bolls in field trials of transgenic plants expressing
      both inhibitors. Better crop protection thus is achieved using combinations of
      inhibitors in which one class of proteinase inhibitor is used to match the
      genetic capacity of an insect to adapt to a second class of proteinase inhibitor.

PMID- 20696896
TI  - Tracing the protectors path from the germ line to the genome.
AB  - One of the basic principles that nature uses in evolution is to recycle
      successful concepts and create new functions by modifying existing units. This
      conservatism in evolution has resulted in an astonishingly high sequence identity
      of genes, even between evolutionarily distant species such as the nematode
      Caenorhabditis elegans and Homo sapiens. The recycling of successful concepts in
      conjunction with gene duplication events has also led to the existence of highly
      homologous proteins within the genome of many species. Often, these homologous
      proteins show similar, yet distinct functions that, in combination with their
      individual tissue distribution, define their specific physiological role. One
      prominent example is the p53 protein family, which consists of p53, p63, and p73.
      Recent advances in understanding the specific biological functions of these
      members have shed some light onto the evolution of this crucial protein family,
      from a germ line-specific quality-control factor to a somatic tumor suppressor.
      Furthermore, structures of the oligomerization domains of the mammalian paralogs,
      p53 and p73, and invertebrate orthologs, CEP-1 and DMP53, have delineated
      evolutionary changes and revealed that the oligomerization domain of p53 lacks
      additional stabilizing structural elements present in all other p53 family
      members. This suggests that p53 is the most recent evolutionary member of this
      protein family and predicts a mechanism for p53 activation.

PMID- 20696897
TI  - Magnetic resonance monitoring of focused ultrasound/magnetic nanoparticle
      targeting delivery of therapeutic agents to the brain.
AB  - The superparamagnetic properties of magnetic nanoparticles (MNPs) allow them to
      be guided by an externally positioned magnet and also provide contrast for MRI.
      However, their therapeutic use in treating CNS pathologies in vivo is limited by
      insufficient local accumulation and retention resulting from their inability to
      traverse biological barriers. The combined use of focused ultrasound and magnetic
      targeting synergistically delivers therapeutic MNPs across the blood-brain
      barrier to enter the brain both passively and actively. Therapeutic MNPs were
      characterized and evaluated both in vitro and in vivo, and MRI was used to
      monitor and quantify their distribution in vivo. The technique could be used in
      normal brains or in those with tumors, and significantly increased the deposition
      of therapeutic MNPs in brains with intact or compromised blood-brain barriers.
      Synergistic targeting and image monitoring are powerful techniques for the
      delivery of macromolecular chemotherapeutic agents into the CNS under the
      guidance of MRI.

PMID- 20696898
TI  - Sleep homeostasis in the rat is preserved during chronic sleep restriction.
AB  - Sleep is homeostatically regulated in all animal species that have been carefully
      studied so far. The best characterized marker of sleep homeostasis is slow wave
      activity (SWA), the EEG power between 0.5 and 4 Hz during nonrapid eye movement
      (NREM) sleep. SWA reflects the accumulation of sleep pressure as a function of
      duration and/or intensity of prior wake: it increases after spontaneous wake and
      short-term (3-24 h) sleep deprivation and decreases during sleep. However, recent
      evidence suggests that during chronic sleep restriction (SR) sleep may be
      regulated by both allostatic and homeostatic mechanisms. Here, we performed
      continuous, almost completely artifact-free EEG recordings from frontal,
      parietal, and occipital cortex in freely moving rats (n = 11) during and after 5
      d of SR. During SR, rats were allowed to sleep during the first 4 h of the light
      period (4S(+)) but not during the following 20 h (20S(-)). During the daily 20S(
      ) most sleep was prevented, whereas the number of short (<20 s) sleep attempts
      increased. Low-frequency EEG power (1-6 Hz) in both sleep and wake also increased
      during 20S(-), most notably in the occipital cortex. In all animals NREM SWA
      increased above baseline levels during the 4S(+) periods and in post-SR recovery.
      The SWA increase was more pronounced in frontal cortex, and its magnitude was
      determined by the efficiency of SR. Analysis of cumulative slow wave energy
      demonstrated that the loss of SWA during SR was compensated by the end of the
      second recovery day. Thus, the homeostatic regulation of sleep is preserved under
      conditions of chronic SR.

PMID- 20696899
TI  - TCF4 and CDX2, major transcription factors for intestinal function, converge on
      the same cis-regulatory regions.
AB  - Surprisingly few pathways signal between cells, raising questions about
      mechanisms for tissue-specific responses. In particular, Wnt ligands signal in
      many mammalian tissues, including the intestinal epithelium, where constitutive
      signaling causes cancer. Genome-wide analysis of DNA cis-regulatory regions bound
      by the intestine-restricted transcription factor CDX2 in colonic cells uncovered
      highly significant overrepresentation of sequences that bind TCF4, a
      transcriptional effector of intestinal Wnt signaling. Chromatin
      immunoprecipitation confirmed TCF4 occupancy at most such sites and co-occupancy
      of CDX2 and TCF4 across short distances. A region spanning the single nucleotide
      polymorphism rs6983267, which lies within a MYC enhancer and confers colorectal
      cancer risk in humans, represented one of many co-occupied sites. Co-occupancy
      correlated with intestine-specific gene expression and CDX2 loss reduced TCF4
      binding. These results implicate CDX2 in directing TCF4 binding in intestinal
      cells. Co-occupancy of regulatory regions by signal-effector and tissue
      restricted transcription factors may represent a general mechanism for ubiquitous
      signaling pathways to achieve tissue-specific outcomes.

PMID- 20696900
TI  - PARK2 deletions occur frequently in sporadic colorectal cancer and accelerate
      adenoma development in Apc mutant mice.
AB  - In 100 primary colorectal carcinomas, we demonstrate by array comparative genomic
      hybridization (aCGH) that 33% show DNA copy number (DCN) loss involving PARK2,
      the gene encoding PARKIN, the E3 ubiquitin ligase whose deficiency is responsible
      for a form of autosomal recessive juvenile parkinsonism. PARK2 is located on
      chromosome 6 (at 6q25-27), a chromosome with one of the lowest overall
      frequencies of DNA copy number alterations recorded in colorectal cancers. The
      PARK2 deletions are mostly focal (31% approximately 0.5 Mb on average),
      heterozygous, and show maximum incidence in exons 3 and 4. As PARK2 lies within
      FRA6E, a large common fragile site, it has been argued that the observed DCN
      losses in PARK2 in cancer may represent merely the result of enforced replication
      of locally vulnerable DNA. However, we show that deficiency in expression of
      PARK2 is significantly associated with adenomatous polyposis coli (APC)
      deficiency in human colorectal cancer. Evidence of some PARK2 mutations and
      promoter hypermethylation is described. PARK2 overexpression inhibits cell
      proliferation in vitro. Moreover, interbreeding of Park2 heterozygous knockout
      mice with Apc(Min) mice resulted in a dramatic acceleration of intestinal adenoma
      development and increased polyp multiplicity. We conclude that PARK2 is a tumor
      suppressor gene whose haploinsufficiency cooperates with mutant APC in colorectal
      carcinogenesis.

PMID- 20696901
TI  - Small-molecule inducers of insulin expression in pancreatic alpha-cells.
AB  - High-content screening for small-molecule inducers of insulin expression
      identified the compound BRD7389, which caused alpha-cells to adopt several
      morphological and gene expression features of a beta-cell state. Assay
      performance profile analysis suggests kinase inhibition as a mechanism of action,
      and we show that biochemical and cellular inhibition of the RSK kinase family by
      BRD7389 is likely related to its ability induce a beta-cell-like state. BRD7389
      also increases the endocrine cell content and function of donor human pancreatic
      islets in culture.

PMID- 20696902
TI  - Carbohydrate-binding modules promote the enzymatic deconstruction of intact plant
      cell walls by targeting and proximity effects.
AB  - Cell wall degrading enzymes have a complex molecular architecture consisting of
      catalytic modules and noncatalytic carbohydrate-binding modules (CBMs). The
      function of CBMs in cell wall degrading processes is poorly understood. Here, we
      have evaluated the potential enzyme-targeting function of CBMs in the context of
      intact primary and secondary cell wall deconstruction. The capacity of a pectate
      lyase to degrade pectic homogalacturonan in primary cell walls was potentiated by
      cellulose-directed CBMs but not by xylan-directed CBMs. Conversely, the
      arabinofuranosidase-mediated removal of side chains from arabinoxylan in xylan
      rich and cellulose-poor wheat grain endosperm cell walls was enhanced by a xylan
      binding CBM but less so by a crystalline cellulose-specific module. The capacity
      of xylanases to degrade xylan in secondary cell walls was potentiated by both
      xylan- and cellulose-directed CBMs. These studies demonstrate that CBMs can
      potentiate the action of a cognate catalytic module toward polysaccharides in
      intact cell walls through the recognition of nonsubstrate polysaccharides. The
      targeting actions of CBMs therefore have strong proximity effects within cell
      wall structures, explaining why cellulose-directed CBMs are appended to many
      noncellulase cell wall hydrolases.

PMID- 20696903
TI  - Vinca drug components accumulate exclusively in leaf exudates of Madagascar
      periwinkle.
AB  - The monoterpenoid indole alkaloids (MIAs) of Madagascar periwinkle (Catharanthus
      roseus) continue to be the most important source of natural drugs in chemotherapy
      treatments for a range of human cancers. These anticancer drugs are derived from
      the coupling of catharanthine and vindoline to yield powerful dimeric MIAs that
      prevent cell division. However the precise mechanisms for their assembly within
      plants remain obscure. Here we report that the complex development-, environment
      , organ-, and cell-specific controls involved in expression of MIA pathways are
      coupled to secretory mechanisms that keep catharanthine and vindoline separated
      from each other in living plants. Although the entire production of catharanthine
      and vindoline occurs in young developing leaves, catharanthine accumulates in
      leaf wax exudates of leaves, whereas vindoline is found within leaf cells. The
      spatial separation of these two MIAs provides a biological explanation for the
      low levels of dimeric anticancer drugs found in the plant that result in their
      high cost of commercial production. The ability of catharanthine to inhibit the
      growth of fungal zoospores at physiological concentrations found on the leaf
      surface of Catharanthus leaves, as well as its insect toxicity, provide an
      additional biological role for its secretion. We anticipate that this discovery
      will trigger a broad search for plants that secrete alkaloids, the biological
      mechanisms involved in their secretion to the plant surface, and the ecological
      roles played by them.

PMID- 20696904
TI  - Cortical depth-specific microvascular dilation underlies laminar differences in
      blood oxygenation level-dependent functional MRI signal.
AB  - Changes in neuronal activity are accompanied by the release of vasoactive
      mediators that cause microscopic dilation and constriction of the cerebral
      microvasculature and are manifested in macroscopic blood oxygenation level
      dependent (BOLD) functional MRI (fMRI) signals. We used two-photon microscopy to
      measure the diameters of single arterioles and capillaries at different depths
      within the rat primary somatosensory cortex. These measurements were compared
      with cortical depth-resolved fMRI signal changes. Our microscopic results
      demonstrate a spatial gradient of dilation onset and peak times consistent with
      "upstream" propagation of vasodilation toward the cortical surface along the
      diving arterioles and "downstream" propagation into local capillary beds. The
      observed BOLD response exhibited the fastest onset in deep layers, and the
      "initial dip" was most pronounced in layer I. The present results indicate that
      both the onset of the BOLD response and the initial dip depend on cortical depth
      and can be explained, at least in part, by the spatial gradient of delays in
      microvascular dilation, the fastest response being in the deep layers and the
      most delayed response in the capillary bed of layer I.

PMID- 20696905
TI  - Caloric restriction or catalase inactivation extends yeast chronological lifespan
      by inducing H2O2 and superoxide dismutase activity.
AB  - The free radical theory of aging posits oxidative damage to macromolecules as a
      primary determinant of lifespan. Recent studies challenge this theory by
      demonstrating that in some cases, longevity is enhanced by inactivation of
      oxidative stress defenses or is correlated with increased, rather than decreased
      reactive oxygen species and oxidative damage. Here we show that, in Saccharomyces
      cerevisiae, caloric restriction or inactivation of catalases extends
      chronological lifespan by inducing elevated levels of the reactive oxygen species
      hydrogen peroxide, which activate superoxide dismutases that inhibit the
      accumulation of superoxide anions. Increased hydrogen peroxide in catalase
      deficient cells extends chronological lifespan despite parallel increases in
      oxidative damage. These findings establish a role for hormesis effects of
      hydrogen peroxide in promoting longevity that have broad implications for
      understanding aging and age-related diseases.

PMID- 20696906
TI  - Cullin 4-ring finger-ligase plays a key role in the control of endoreplication
      cycles in Arabidopsis trichomes.
AB  - One of the predominant cell-cycle programs found in mature tissues is
      endoreplication, also known as endoreduplication, that leads to cellular
      polyploidy. A key question for the understanding of endoreplication cycles is how
      oscillating levels of cyclin-dependent kinase activity are generated that control
      repeated rounds of DNA replication. The APC/C performs a pivotal function in the
      mitotic cell cycle by promoting anaphase and paving the road for a new round of
      DNA replication. However, using marker lines and plants in which APC/C components
      are knocked down, we show here that outgrowing and endoreplicating Arabidopsis
      leaf hairs display no or very little APC/C activity. Instead we find that RBX1
      containing Cullin-RING E3 ubiquitin-Ligases (CRLs) are of central importance for
      the progression through endoreplication cycles; in particular, we have identified
      CULLIN4 as a major regulator of endoreplication in Arabidopsis trichomes. We have
      incorporated our findings into a bio-mathematical simulation presenting a robust
      two-step model of endoreplication control with one type of cyclin-dependent
      kinase inhibitor function for entry and a CRL-dependent oscillation of cyclin
      dependent kinase activity via degradation of a second type of CDK inhibitor
      during endoreplication cycles.

PMID- 20696908
TI  - Rice yields in tropical/subtropical Asia exhibit large but opposing sensitivities
      to minimum and maximum temperatures.
AB  - Data from farmer-managed fields have not been used previously to disentangle the
      impacts of daily minimum and maximum temperatures and solar radiation on rice
      yields in tropical/subtropical Asia. We used a multiple regression model to
      analyze data from 227 intensively managed irrigated rice farms in six important
      rice-producing countries. The farm-level detail, observed over multiple growing
      seasons, enabled us to construct farm-specific weather variables, control for
      unobserved factors that either were unique to each farm but did not vary over
      time or were common to all farms at a given site but varied by season and year,
      and obtain more precise estimates by including farm- and site-specific economic
      variables. Temperature and radiation had statistically significant impacts during
      both the vegetative and ripening phases of the rice plant. Higher minimum
      temperature reduced yield, whereas higher maximum temperature raised it;
      radiation impact varied by growth phase. Combined, these effects imply that yield
      at most sites would have grown more rapidly during the high-yielding season but
      less rapidly during the low-yielding season if observed temperature and radiation
      trends at the end of the 20th century had not occurred, with temperature trends
      being more influential. Looking ahead, they imply a net negative impact on yield
      from moderate warming in coming decades. Beyond that, the impact would likely
      become more negative, because prior research indicates that the impact of maximum
      temperature becomes negative at higher levels. Diurnal temperature variation must
      be considered when investigating the impacts of climate change on irrigated rice
      in Asia.

PMID- 20696907
TI  - Identification of RING finger protein 4 (RNF4) as a modulator of DNA
      demethylation through a functional genomics screen.
AB  - DNA methylation is an important epigenetic modification involved in
      transcriptional regulation, nuclear organization, development, aging, and
      disease. Although DNA methyltransferases have been characterized, the mechanisms
      for DNA demethylation remain poorly understood. Using a cell-based reporter
      assay, we performed a functional genomics screen to identify genes involved in
      DNA demethylation. Here we show that RNF4 (RING finger protein 4), a SUMO
      dependent ubiquitin E3-ligase previously implicated in maintaining genome
      stability, plays a key role in active DNA demethylation. RNF4 reactivates
      methylation-silenced reporters and promotes global DNA demethylation. Rnf4
      deficiency is embryonic lethal with higher levels of methylation in genomic DNA.
      Mechanistic studies show that RNF4 interacts with and requires the base excision
      repair enzymes TDG and APE1 for active demethylation. This activity appears to
      occur by enhancing the enzymatic activities that repair DNA G:T mismatches
      generated from methylcytosine deamination. Collectively, our study reveals a
      unique function for RNF4, which may serve as a direct link between epigenetic DNA
      demethylation and DNA repair in mammalian cells.

PMID- 20696909
TI  - Ectopic vesicular neurotransmitter release along sensory axons mediates
      neurovascular coupling via glial calcium signaling.
AB  - Neurotransmitter release generally is considered to occur at active zones of
      synapses, and ectopic release of neurotransmitters has been demonstrated in a few
      instances. However, the mechanism of ectopic neurotransmitter release is poorly
      understood. We took advantage of the intimate morphological and functional
      proximity of olfactory receptor axons and specialized glial cells, olfactory
      ensheathing cells (OECs), to study ectopic neurotransmitter release. Axonal
      stimulation evoked purinergic and glutamatergic Ca(2+) responses in OECs,
      indicating ATP and glutamate release. In axons expressing synapto-pHluorin,
      stimulation evoked an increase in synapto-pHluorin fluorescence, indicative of
      vesicle fusion. Transmitter release was dependent on Ca(2+) and could be
      inhibited by bafilomycin A1 and botulinum toxin A. Ca(2+) transients in OECs
      evoked by ATP, axonal stimulation, and laser photolysis of NP-EGTA resulted in
      constriction of adjacent blood vessels. Our results indicate that ATP and
      glutamate are released ectopically by vesicles along axons and mediate
      neurovascular coupling via glial Ca(2+) signaling.

PMID- 20696910
TI  - A small RNA promotes siderophore production through transcriptional and metabolic
      remodeling.
AB  - Siderophores are essential factors for iron (Fe) acquisition in bacteria during
      colonization and infection of eukaryotic hosts, which restrain iron access
      through iron-binding protein, such as lactoferrin and transferrin. The synthesis
      of siderophores by Escherichia coli is considered to be fully regulated at the
      transcriptional level by the Fe-responsive transcriptional repressor Fur. Here we
      characterized two different pathways that promote the production of the
      siderophore enterobactin via the action of the small RNA RyhB. First, RyhB is
      required for normal expression of an important enterobactin biosynthesis
      polycistron, entCEBAH. Second, RyhB directly represses the translation of cysE,
      which encodes a serine acetyltransferase that uses serine as a substrate for
      cysteine biosynthesis. Reduction of CysE activity by RyhB allows serine to be
      used as building blocks for enterobactin synthesis through the nonribosomal
      peptide synthesis pathway. Thus, RyhB plays an essential role in siderophore
      production and may modulate bacterial virulence through optimization of
      siderophore production.

PMID- 20696911
TI  - Evidence of intense ongoing endemic transmission of hepatitis C virus in Egypt.
AB  - Egypt has the highest prevalence of antibodies to hepatitis C virus (HCV) in the
      world, estimated nationally at 14.7%. An estimated 9.8% are chronically infected.
      Numerous HCV prevalence studies in Egypt have published various estimates from
      different Egyptian communities, suggesting that Egypt, relative to the other
      nations of the world, might be experiencing intense ongoing HCV transmission.
      More importantly, a new national study provided an opportunity to apply
      established epidemiologic models to estimate incidence. Validated mathematical
      models for estimating incidence from age-specific prevalence were used. All
      previous prevalence studies of HCV in Egypt were reviewed and used to estimate
      incidence provided that there was sufficient age-specific data required by the
      models. All reports of anti-HCV antibody prevalence were much higher than any
      single other national estimate. Age was the strongest and most consistently
      associated factor to HCV prevalence and HCV RNA positivity. It was not possible
      to establish a prior reference point for HCV prevalence or incidence to compare
      with the 2009 incidence estimates. The modeled incidence from the national study
      and collectively from the modeled incidence from the previous community studies
      was 6.9/1,000 [95% confidence interval (CI), 5.5-7.4] per person per year and
      6.6/1,000 (95% CI, 5.1-7.0) per person per year, respectively. Projected to the
      age structure of the Egyptian population, more than 500,000 new HCV infections
      per year were estimated. Iatrogenic transmission is the most likely, underlining
      exposure to the ongoing transmission. The study demonstrates the urgency to
      reduce HCV transmission in Egypt.

PMID- 20696913
TI  - Influence of climate on malaria transmission depends on daily temperature
      variation.
AB  - Malaria transmission is strongly influenced by environmental temperature, but the
      biological drivers remain poorly quantified. Most studies analyzing malaria
      temperature relations, including those investigating malaria risk and the
      possible impacts of climate change, are based solely on mean temperatures and
      extrapolate from functions determined under unrealistic laboratory conditions.
      Here, we present empirical evidence to show that, in addition to mean
      temperatures, daily fluctuations in temperature affect parasite infection, the
      rate of parasite development, and the essential elements of mosquito biology that
      combine to determine malaria transmission intensity. In general, we find that,
      compared with rates at equivalent constant mean temperatures, temperature
      fluctuation around low mean temperatures acts to speed up rate processes, whereas
      fluctuation around high mean temperatures acts to slow processes down. At the
      extremes (conditions representative of the fringes of malaria transmission, where
      range expansions or contractions will occur), fluctuation makes transmission
      possible at lower mean temperatures than currently predicted and can potentially
      block transmission at higher mean temperatures. If we are to optimize control
      efforts and develop appropriate adaptation or mitigation strategies for future
      climates, we need to incorporate into predictive models the effects of daily
      temperature variation and how that variation is altered by climate change.

PMID- 20696912
TI  - AtsPLA2-alpha nuclear relocalization by the Arabidopsis transcription factor
      AtMYB30 leads to repression of the plant defense response.
AB  - The hypersensitive response (HR), characterized by a rapid and localized cell
      death at the inoculation site, is one of the most efficient resistance reactions
      to pathogen attack in plants. The transcription factor AtMYB30 was identified as
      a positive regulator of the HR and resistance responses during interactions
      between Arabidopsis and bacteria. Here, we show that AtMYB30 and the secreted
      phospholipase AtsPLA(2)-alpha physically interact in vivo, following the AtMYB30
      mediated specific relocalization of AtsPLA(2)-alpha from cytoplasmic vesicles to
      the plant cell nucleus. This protein interaction leads to repression of AtMYB30
      transcriptional activity and negative regulation of plant HR. Moreover, Atspla(2)
      alpha mutant plants are more resistant to bacterial inoculation, whereas
      AtsPLA(2)-alpha overexpression leads to decreased resistance, confirming that
      AtsPLA(2)-alpha is a negative regulator of AtMYB30-mediated defense. These data
      underline the importance of cellular dynamics and, particularly, protein
      translocation to the nucleus, for defense-associated gene regulation in plants.

PMID- 20696914
TI  - Defective feedback regulation of NF-kappaB underlies Sjogren's syndrome in mice
      with mutated kappaB enhancers of the IkappaBalpha promoter.
AB  - Feedback regulation of transcription factor NF-kappaB by its inhibitor
      IkappaBalpha plays an essential role in control of NF-kappaB activity. To
      understand the biological significance of IkappaBalpha-mediated feedback
      regulation of NF-kappaB, we generated mice harboring mutated kappaB enhancers in
      the promoter of the IkappaBalpha gene (IkappaBalpha(M/M)) to inhibit NF-kappaB
      regulated IkappaBalpha expression. Here, we report that these mutant mice are
      defective in NF-kappaB-induced expression of IkappaBalpha. This defective
      feedback regulation of NF-kappaB by IkappaBalpha not only altered activity of NF
      kappaB, but also the expression of NF-kappaB-regulated genes. As a result,
      IkappaBalpha(M/M), the homozygous knock-in mice with mutated kappaB enhancers in
      the IkappaBalpha promoter, acquire shorten life span, hypersensitivity to septic
      shock, abnormal T-cell development and activation, and Sjogren's Syndrome. These
      findings therefore demonstrate that the IkappaBalpha-mediated feedback regulation
      of NF-kappaB has an essential role in controlling T-cell development and
      functions, provide mechanistic insight into the development of Sjogren's
      Syndrome, and suggest the potential of NF-kappaB signaling as a therapeutic
      target for Sjogren's Syndrome and other autoimmune diseases.

PMID- 20696915
TI  - Severe anemia in the Nan mutant mouse caused by sequence-selective disruption of
      erythroid Kruppel-like factor.
AB  - Studies of mouse models of anemia have long provided fundamental insights into
      red blood cell formation and function. Here we show that the semidominant mouse
      mutation Nan ("neonatal anemia") carries a single amino acid change (E339D)
      within the second zinc finger of the erythroid Kruppel-like factor (EKLF), a
      critical erythroid regulatory transcription factor. The mutation alters the DNA
      binding specificity of EKLF so that it no longer binds promoters of a subset of
      its DNA targets. Remarkably, even when mutant Nan and wild-type EKLF alleles are
      expressed at equivalent levels, the mutant form selectively interferes with
      expression of EKLF target genes whose promoter elements it no longer binds. This
      interference yields a distorted genetic output and selective protein deficiencies
      that differ from those seen in EKLF-heterozygous and EKLF-null red blood cells
      and presents a unique and unexpected mechanism of inherited disease.

PMID- 20696916
TI  - AIDS-protective HLA-B*27/B*57 and chimpanzee MHC class I molecules target
      analogous conserved areas of HIV-1/SIVcpz.
AB  - In the absence of treatment, most HIV-1-infected humans develop AIDS. However, a
      minority are long-term nonprogressors, and resistance is associated with the
      presence of particular HLA-B*27/B*57 molecules. In contrast, most HIV-1-infected
      chimpanzees do not contract AIDS. In comparison with humans, chimpanzees
      experienced an ancient selective sweep affecting the MHC class I repertoire. We
      have determined the peptide-binding properties of frequent chimpanzee MHC class I
      molecules, and show that, like HLA-B*27/B*57, they target similar conserved areas
      of HIV-1/SIV(cpz). In addition, many animals appear to possess multiple molecules
      targeting various conserved areas of the HIV-1/SIV(cpz) Gag protein, a
      quantitative aspect of the immune response that may further minimize the chance
      of viral escape. The functional characteristics of the contemporary chimpanzee
      MHC repertoire suggest that the selective sweep was caused by a lentiviral
      pandemic.

PMID- 20696918
TI  - T-cell receptor complex is essential for Fas signal transduction.
AB  - The Fas receptor (also known as CD95 and APO-1) is a member of the tumor necrosis
      factor alpha-family of death receptors that mediate T-cell responses. Here, we
      show that Fas receptor signaling requires a functional T-cell receptor (TCR)
      complex. Fas receptor directly binds to and activates TCR components in a
      stimulus-dependent manner. Fas receptor stimulation does not activate canonical
      downstream TCR pathways, but instead the TCR complex is required specifically for
      Fas-mediated calcium release. Importantly, null mutations in Lck, ZAP70, and the
      TCR alpha- and beta-chains abrogate Fas signaling. Our results reveal a direct
      role for the TCR complex in mediating Fas-specific signaling events critical for
      T-cell homeostasis.

PMID- 20696917
TI  - Proangiogenic scaffolds as functional templates for cardiac tissue engineering.
AB  - We demonstrate here a cardiac tissue-engineering strategy addressing
      multicellular organization, integration into host myocardium, and directional
      cues to reconstruct the functional architecture of heart muscle. Microtemplating
      is used to shape poly(2-hydroxyethyl methacrylate-co-methacrylic acid) hydrogel
      into a tissue-engineering scaffold with architectures driving heart tissue
      integration. The construct contains parallel channels to organize cardiomyocyte
      bundles, supported by micrometer-sized, spherical, interconnected pores that
      enhance angiogenesis while reducing scarring. Surface-modified scaffolds were
      seeded with human ES cell-derived cardiomyocytes and cultured in vitro.
      Cardiomyocytes survived and proliferated for 2 wk in scaffolds, reaching adult
      heart densities. Cardiac implantation of acellular scaffolds with pore diameters
      of 30-40 microm showed angiogenesis and reduced fibrotic response, coinciding
      with a shift in macrophage phenotype toward the M2 state. This work establishes a
      foundation for spatially controlled cardiac tissue engineering by providing
      discrete compartments for cardiomyocytes and stroma in a scaffold that enhances
      vascularization and integration while controlling the inflammatory response.

PMID- 20696920
TI  - Profile of Thure E. Cerling.

PMID- 20696919
TI  - Fine analysis of spontaneous MAGE-C1/CT7-specific immunity in melanoma patients.
AB  - Cancer/testis (CT) antigens represent prime candidates for immunotherapy in
      cancer patients, because their expression is restricted to cancer cells and germ
      cells of the testis. MAGE-C1/CT7 is a CT antigen that is highly expressed in
      several types of cancers. Spontaneous occurrence of CT7-specific antibodies was
      previously detected by SEREX screen in a melanoma patient. However, naturally
      occurring CT7-specific T-cell responses have thus far not been detected.
      Peripheral blood mononuclear cells (PBMCs) from 26 metastatic melanoma patients
      expressing CT7 in their tumor lesions (CT7(+)) were analyzed for CT7-specific T
      cell responses using overlapping peptides. CT7-specific CD4(+) T-cell responses
      were detected in three patients (11.5%). These CT7-specific CD4(+) T-cell
      responses were detectable in melanoma patients' PBMCs exclusively from
      preexisting CD45RA(-) memory CD4(+) T-cell pool. Additional CT7-specific memory
      CD4(+) T-cell responses were detected in CT7(+) melanoma patients after depletion
      of CD4(+)CD25high Treg cells showing that Treg cells impact on CT7-specific
      CD4(+) T cells in melanoma patients. CT7-specific CD4(+) T-cell clones were
      generated and used to define minimal epitopes, restriction elements, and confirm
      the recognition of naturally processed antigen. Surprisingly, these clones were
      able to secrete perforin and exert cytotoxicity. This study shows that CT7 can
      induce specific cellular immunity in melanoma patients. Based on these findings,
      CT7 will be further explored as a potential vaccine for melanoma immunotherapy.

PMID- 20696921
TI  - Molecular basis for the resistance of an insect chymotrypsin to a potato type II
      proteinase inhibitor.
AB  - Plants produce a variety of proteinase inhibitors (PIs) that have a major
      function in defense against insect herbivores. In turn, insects have developed
      strategies to minimize the effect of dietary PIs on digestion. We have discovered
      that Helicoverpa larvae that survive consumption of a multidomain serine PI from
      Nicotiana alata (NaPI) contain high levels of a chymotrypsin that is not
      inhibited by NaPI. Here we describe the isolation of this NaPI-resistant
      chymotrypsin and an NaPI-susceptible chymotrypsin from Helicoverpa larvae,
      together with their corresponding cDNAs. We investigated the mechanism of
      resistance by mutating selected positions of the NaPI-susceptible chymotrypsin
      using the corresponding amino acids of the NaPI-resistant chymotrypsin. Four
      critical residues that conferred resistance to NaPI were identified. Molecular
      modeling revealed that a Phe-->Leu substitution at position 37 in the
      chymotrypsin results in the loss of important binding contacts with NaPI.
      Identification of the molecular mechanisms that contribute to PI resistance in
      insect digestive proteases will enable us to develop better inhibitors for the
      control of lepidopteran species that are major agricultural pests worldwide.

PMID- 20696922
TI  - Profile of Ivan Izquierdo.

PMID- 20696923
TI  - Specific involvement of postsynaptic GluN2B-containing NMDA receptors in the
      developmental elimination of corticospinal synapses.
AB  - The GluN2B (GluRepsilon2/NR2B) and GluN2A (GluRepsilon1/NR2A) NMDA receptor
      (NMDAR) subtypes have been differentially implicated in activity-dependent
      synaptic plasticity. However, little is known about the respective contributions
      made by these two subtypes to developmental plasticity, in part because studies
      of GluN2B KO [Grin2b(-/-) (2b(-/-))] mice are hampered by early neonatal
      mortality. We previously used in vitro slice cocultures of rodent cerebral cortex
      (Cx) and spinal cord (SpC) to show that corticospinal (CS) synapses, once present
      throughout the SpC, are eliminated from the ventral side during development in an
      NMDAR-dependent manner. To study subtype specificity of NMDAR in this
      developmental plasticity, we cocultured Cx and SpC slices derived from postnatal
      day 0 (P0) animals with different genotypes [2b(-/-), Grin2a(-/-) (2a(-/-)), or
      WT mice]. The distribution of CS synapses was studied electrophysiologically and
      with a voltage-sensitive dye. Synapse elimination on the ventral side was blocked
      in WT(Cx)-2b(-/-)(SpC) pairs but not in WT(Cx)-2a(-/-)(SpC) or 2b(-/-)(Cx)
      WT(SpC) pairs. CS axonal regression was also observed through live imaging of CS
      axons labeled with enhanced yellow fluorescent protein (EYFP) through exo utero
      electroporation. These findings suggest that postsynaptic GluN2B is selectively
      involved in CS synapse elimination. In addition, the elimination was not blocked
      in 2a(-/-) SpC slices, where Ca(2+) entry through GluN2B-mediated CS synaptic
      currents was reduced to the same level as in 2b(-/-) slices, suggesting that the
      differential effect of GluN2B and GluN2A in CS synapse elimination might not be
      explained based solely on greater Ca(2+) entry through GluN2B-containing
      channels.

PMID- 20696924
TI  - Economic choices can be made using only stimulus values.
AB  - Decision-making often involves choices between different stimuli, each of which
      is associated with a different physical action. A growing consensus suggests that
      the brain makes such decisions by assigning a value to each available option and
      then comparing them to make a choice. An open question in decision neuroscience
      is whether the brain computes these choices by comparing the values of stimuli
      directly in goods space or instead by first assigning values to the associated
      actions and then making a choice over actions. We used a functional MRI paradigm
      in which human subjects made choices between different stimuli with and without
      knowledge of the actions required to obtain the different stimuli. We found
      neural correlates of the value of the chosen stimulus (a postdecision signal) in
      ventromedial prefrontal cortex before the actual stimulus-action pairing was
      revealed. These findings provide support for the hypothesis that the brain is
      capable of making choices in the space of goods without first transferring values
      into action space.

PMID- 20696925
TI  - Bridging the gap between ribosomal and nonribosomal protein synthesis.

PMID- 20696926
TI  - Missense mutations in dystrophin that trigger muscular dystrophy decrease protein
      stability and lead to cross-beta aggregates.
AB  - A deficiency of functional dystrophin protein in muscle cells causes muscular
      dystrophy (MD). More than 50% of missense mutations that trigger the disease
      occur in the N-terminal actin binding domain (N-ABD or ABD1). We examined the
      effect of four disease-causing mutations--L54R, A168D, A171P, and Y231N--on the
      structural and biophysical properties of isolated N-ABD. Our results indicate
      that N-ABD is a monomeric, well-folded alpha-helical protein in solution, as is
      evident from its alpha-helical circular dichroism spectrum, blue shift of the
      native state tryptophan fluorescence, well-dispersed amide crosspeaks in 2D NMR
      (15)N-(1)H HSQC fingerprint region, and rotational correlation time calculated
      from NMR longitudinal (T(1)) and transverse (T(2)) relaxation experiments.
      Compared to WT, three mutants--L54R, A168D, and A171P--show a decreased alpha
      helicity and do not show a cooperative sigmoidal melt with temperature,
      indicating that these mutations exist in a wide range of conformations or in a
      "molten globule" state. In contrast, Y231N has an alpha-helical content similar
      to WT and shows a cooperative sigmoidal temperature melt but with a decreased
      stability. All four mutants experience serious misfolding and aggregation. FT-IR,
      circular dichroism, increase in thioflavin T fluorescence, and the congo red
      spectral shift and birefringence show that these aggregates contain
      intermolecular cross-beta structure similar to that found in amyloid diseases.
      These results indicate that disease-causing mutants affect N-ABD structure by
      decreasing its thermodynamic stability and increasing its misfolding, thereby
      decreasing the net functional dystrophin concentration.

PMID- 20696927
TI  - Structure and function of the polymerase core of TRAMP, a RNA surveillance
      complex.
AB  - The Trf4p/Air2p/Mtr4p polyadenylation (TRAMP) complex recognizes aberrant RNAs in
      Saccharomyces cerevisiae and targets them for degradation. A TRAMP subcomplex
      consisting of a noncanonical poly(A) RNA polymerase in the Pol ss superfamily of
      nucleotidyl transferases, Trf4p, and a zinc knuckle protein, Air2p, mediates
      initial substrate recognition. Trf4p and related eukaryotic poly(A) and poly(U)
      polymerases differ from other characterized enzymes in the Pol ss superfamily
      both in sequence and in the lack of recognizable nucleic acid binding motifs.
      Here we report, at 2.7-A resolution, the structure of Trf4p in complex with a
      fragment of Air2p comprising two zinc knuckle motifs. Trf4p consists of a
      catalytic and central domain similar in fold to those of other noncanonical Pol
      beta RNA polymerases, and the two zinc knuckle motifs of Air2p interact with the
      Trf4p central domain. The interaction surface on Trf4p is highly conserved across
      eukaryotes, providing evidence that the Trf4p/Air2p complex is conserved in
      higher eukaryotes as well as in yeast and that the TRAMP complex may also
      function in RNA surveillance in higher eukaryotes. We show that Air2p, and in
      particular sequences encompassing a zinc knuckle motif near its N terminus,
      modulate Trf4p activity, and we present data supporting a role for this zinc
      knuckle in RNA binding. Finally, we show that the RNA 3' end plays a role in
      substrate recognition.

PMID- 20696928
TI  - Dysregulation of the mevalonate pathway promotes transformation.
AB  - The importance of cancer metabolism has been appreciated for many years, but the
      intricacies of how metabolic pathways interconnect with oncogenic signaling are
      not fully understood. With a clear understanding of how metabolism contributes to
      tumorigenesis, we will be better able to integrate the targeting of these
      fundamental biochemical pathways into patient care. The mevalonate (MVA) pathway,
      paced by its rate-limiting enzyme, hydroxymethylglutaryl coenzyme A reductase
      (HMGCR), is required for the generation of several fundamental end-products
      including cholesterol and isoprenoids. Despite years of extensive research from
      the perspective of cardiovascular disease, the contribution of a dysregulated MVA
      pathway to human cancer remains largely unexplored. We address this issue
      directly by showing that dysregulation of the MVA pathway, achieved by ectopic
      expression of either full-length HMGCR or its novel splice variant, promotes
      transformation. Ectopic HMGCR accentuates growth of transformed and
      nontransformed cells under anchorage-independent conditions or as xenografts in
      immunocompromised mice and, importantly, cooperates with RAS to drive the
      transformation of primary mouse embryonic fibroblasts cells. We further explore
      whether the MVA pathway may play a role in the etiology of human cancers and show
      that high mRNA levels of HMGCR and additional MVA pathway genes correlate with
      poor prognosis in a meta-analysis of six microarray datasets of primary breast
      cancer. Taken together, our results suggest that HMGCR is a candidate metabolic
      oncogene and provide a molecular rationale for further exploring the statin
      family of HMGCR inhibitors as anticancer agents.

PMID- 20696929
TI  - Imaging in-plane and normal stresses near an interface crack using traction force
      microscopy.
AB  - Colloidal coatings, such as paint, are all around us. However, we know little
      about the mechanics of the film-forming process because the composition and
      properties of drying coatings vary dramatically in space and time. To surmount
      this challenge, we extend traction force microscopy to quantify the spatial
      distribution of all three components of the stress at the interface of two
      materials. We apply this approach to image stress near the tip of a propagating
      interface crack in a drying colloidal coating and extract the stress intensity
      factor.

PMID- 20696930
TI  - Structural basis for high-affinity HER2 receptor binding by an engineered
      protein.
AB  - The human epidermal growth factor receptor 2 (HER2) is specifically overexpressed
      in tumors of several cancers, including an aggressive form of breast cancer. It
      is therefore a target for both cancer diagnostics and therapy. The 58 amino acid
      residue Zher2 affibody molecule was previously engineered as a high-affinity
      binder of HER2. Here we determined the structure of Zher2 in solution and the
      crystal structure of Zher2 in complex with the HER2 extracellular domain. Zher2
      binds to a conformational epitope on HER2 that is distant from those recognized
      by the therapeutic antibodies trastuzumab and pertuzumab. Its small size and lack
      of interference may provide Zher2 with advantages for diagnostic use or even for
      delivery of therapeutic agents to HER2-expressing tumors when trastuzumab or
      pertuzumab are already employed. Biophysical characterization shows that Zher2 is
      thermodynamically stable in the folded state yet undergoing conformational
      interconversion on a submillisecond time scale. The data suggest that it is the
      HER2-binding conformation that is formed transiently prior to binding. Still,
      binding is very strong with a dissociation constant K(D) = 22 pM, and perfect
      conformational homogeneity is therefore not necessarily required in engineered
      binding proteins. A comparison of the original Z domain scaffold to free and
      bound Zher2 structures reveals how high-affinity binding has evolved during
      selection and affinity maturation and suggests how a compromise between binding
      surface optimization and stability and dynamics of the unbound state has been
      reached.

PMID- 20696931
TI  - Plasticity of lipid-protein interactions in the function and topogenesis of the
      membrane protein lactose permease from Escherichia coli.
AB  - Phosphatidylcholine (PC) has been widely used in place of naturally occurring
      phosphatidylethanolamine (PE) in reconstitution of bacterial membrane proteins.
      However, PC does not support native structure or function for several
      reconstituted transport proteins. Lactose permease (LacY) of Escherichia coli,
      when reconstituted in E. coli phospholipids, exhibits energy-dependent uphill and
      energy-independent downhill transport function and proper conformation of
      periplasmic domain P7, which is tightly linked to uphill transport function. LacY
      expressed in cells lacking PE and containing only anionic phospholipids exhibits
      only downhill transport and lacks native P7 conformation. Reconstitution of LacY
      in the presence of E. coli-derived PE, but not dioleoyl-PC, results in uphill
      transport. We now show that LacY exhibits uphill transport and native
      conformation of P7 when expressed in a mutant of E. coli in which PC completely
      replaces PE even though the structure is not completely native. E. coli-derived
      PC and synthetic PC species containing at least one saturated fatty acid also
      support the native conformation of P7 dependent on the presence of anionic
      phospholipids. Our results demonstrate that the different effects of PE and PC
      species on LacY structure and function cannot be explained by differences in the
      direct interaction of the lipid head groups with specific amino acid residues
      alone but are due to more complex effects of the physical and chemical properties
      of the lipid environment on protein structure. This conclusion is supported by
      the effect of different lipids on the proper folding of domain P7, which
      indirectly influences uphill transport function.

PMID- 20696932
TI  - Vitamin K epoxide reductase prefers ER membrane-anchored thioredoxin-like redox
      partners.
AB  - Vitamin K epoxide reductase (VKOR) sustains blood coagulation by reducing vitamin
      K epoxide to the hydroquinone, an essential cofactor for the gamma-glutamyl
      carboxylation of many clotting factors. The physiological redox partner of VKOR
      remains uncertain, but is likely a thioredoxin-like protein. Here, we demonstrate
      that human VKOR has the same membrane topology as the enzyme from Synechococcus
      sp., whose crystal structure was recently determined. Our results suggest that,
      during the redox reaction, Cys43 in a luminal loop of human VKOR forms a
      transient disulfide bond with a thioredoxin (Trx)-like protein located in the
      lumen of the endoplasmic reticulum (ER). We screened for redox partners of VKOR
      among the large number of mammalian Trx-like ER proteins by testing a panel of
      these candidates for their ability to form this specific disulfide bond with
      human VKOR. Our results show that VKOR interacts strongly with TMX, an ER
      membrane-anchored Trx-like protein with a unique CPAC active site. Weaker
      interactions were observed with TMX4, a close relative of TMX, and ERp18, the
      smallest Trx-like protein of the ER. We performed a similar screen with Ero1
      alpha, an ER-luminal protein that oxidizes the Trx-like protein disulfide
      isomerase. We found that Ero1-alpha interacts with most of the tested Trx-like
      proteins, although only poorly with the membrane-anchored members of the family.
      Taken together, our results demonstrate that human VKOR employs the same electron
      transfer pathway as its bacterial homologs and that VKORs generally prefer
      membrane-bound Trx-like redox partners.

PMID- 20696933
TI  - Scanning ultrafast electron microscopy.
AB  - Progress has been made in the development of four-dimensional ultrafast electron
      microscopy, which enables space-time imaging of structural dynamics in the
      condensed phase. In ultrafast electron microscopy, the electrons are accelerated,
      typically to 200 keV, and the microscope operates in the transmission mode. Here,
      we report the development of scanning ultrafast electron microscopy using a field
      emission-source configuration. Scanning of pulses is made in the single-electron
      mode, for which the pulse contains at most one or a few electrons, thus achieving
      imaging without the space-charge effect between electrons, and still in ten(s) of
      seconds. For imaging, the secondary electrons from surface structures are
      detected, as demonstrated here for material surfaces and biological specimens. By
      recording backscattered electrons, diffraction patterns from single crystals were
      also obtained. Scanning pulsed-electron microscopy with the acquired
      spatiotemporal resolutions, and its efficient heat-dissipation feature, is now
      poised to provide in situ 4D imaging and with environmental capability.

PMID- 20696934
TI  - Anisotropy of wave propagation in the heart can be modeled by a Riemannian
      electrophysiological metric.
AB  - It is well established that wave propagation in the heart is anisotropic and that
      the ratio of velocities in the three principal directions may be as large as
      v(f)v(s)v(n) approximately 4(fibers)2(sheets)1(normal). We develop an alternative
      view of the heart based on this fact by considering it as a non-Euclidean
      manifold with an electrophysiological(el-) metric based on wave velocity. This
      metric is more natural than the Euclidean metric for some applications, because
      el-distances directly encode wave propagation. We develop a model of wave
      propagation based on this metric; this model ignores higher-order effects like
      the curvature of wavefronts and the effect of the boundary, but still gives good
      predictions of local activation times and replicates many of the observed
      features of isochrones. We characterize this model for the important case of the
      rotational orthotropic anisotropy seen in cardiac tissue and perform numerical
      simulations for a slab of cardiac tissue with rotational orthotropic anisotropy
      and for a model of the ventricles based on diffusion tensor MRI scans of the
      canine heart. Even though the metric has many slow directions, we show that the
      rotation of the fibers leads to fast global activation. In the diffusion tensor
      MRI-based model, with principal velocities 0.25051 m/s, we find examples of
      wavefronts that eventually reach speeds up to 0.9 m/s and average velocities of
      0.7 m/s. We believe that development of this non-Euclidean approach to cardiac
      anatomy and electrophysiology could become an important tool for the
      characterization of the normal and abnormal electrophysiological activity of the
      heart.

PMID- 20696936
TI  - Behavioral dynamics and influence in networked coloring and consensus.
AB  - We report on human-subject experiments on the problems of coloring (a social
      differentiation task) and consensus (a social agreement task) in a networked
      setting. Both tasks can be viewed as coordination games, and despite their
      cognitive similarity, we find that within a parameterized family of social
      networks, network structure elicits opposing behavioral effects in the two
      problems, with increased long-distance connectivity making consensus easier for
      subjects and coloring harder. We investigate the influence that subjects have on
      their network neighbors and the collective outcome, and find that it varies
      considerably, beyond what can be explained by network position alone. We also
      find strong correlations between influence and other features of individual
      subject behavior. In contrast to much of the recent research in network science,
      which often emphasizes network topology out of the context of any specific
      problem and places primacy on network position, our findings highlight the
      potential importance of the details of tasks and individuals in social networks.

PMID- 20696935
TI  - Conformational dynamics of bacteriophage T7 DNA polymerase and its processivity
      factor, Escherichia coli thioredoxin.
AB  - Gene 5 of bacteriophage T7 encodes a DNA polymerase (gp5) responsible for the
      replication of the phage DNA. Gp5 polymerizes nucleotides with low processivity,
      dissociating after the incorporation of 1 to 50 nucleotides. Thioredoxin (trx) of
      Escherichia coli binds tightly (Kd = 5 nM) to a unique segment in the thumb
      subdomain of gp5 and increases processivity. We have probed the molecular basis
      for the increase in processivity. A single-molecule experiment reveals
      differences in rates of enzymatic activity and processivity between gp5 and
      gp5/trx. Small angle X-ray scattering studies combined with nuclease footprinting
      reveal two conformations of gp5, one in the free state and one upon binding to
      trx. Comparative analysis of the DNA binding clefts of DNA polymerases and DNA
      binding proteins show that the binding surface contains more hydrophobic residues
      than other DNA binding proteins. The balanced composition between hydrophobic and
      charged residues of the binding site allows for efficient sliding of gp5/trx on
      the DNA. We propose a model for trx-induced conformational changes in gp5 that
      enhance the processivity by increasing the interaction of gp5 with DNA.

PMID- 20696937
TI  - Polar front shift and atmospheric CO2 during the glacial maximum of the Early
      Paleozoic Icehouse.
AB  - Our new data address the paradox of Late Ordovician glaciation under supposedly
      high pCO(2) (8 to 22x PAL: preindustrial atmospheric level). The
      paleobiogeographical distribution of chitinozoan ("mixed layer") marine
      zooplankton biotopes for the Hirnantian glacial maximum (440 Ma) are
      reconstructed and compared to those from the Sandbian (460 Ma): They demonstrate
      a steeper latitudinal temperature gradient and an equatorwards shift of the Polar
      Front through time from 55 degrees -70 degrees S to approximately 40 degrees S.
      These changes are comparable to those during Pleistocene interglacial-glacial
      cycles. In comparison with the Pleistocene, we hypothesize a significant decline
      in mean global temperature from the Sandbian to Hirnantian, proportional with a
      fall in pCO(2) from a modeled Sandbian level of approximately 8x PAL to
      approximately 5x PAL during the Hirnantian. Our data suggest that a compression
      of midlatitudinal biotopes and ecospace in response to the developing glaciation
      was a likely cause of the end-Ordovician mass extinction.

PMID- 20696938
TI  - Physical and functional interaction between the condensin MukB and the decatenase
      topoisomerase IV in Escherichia coli.
AB  - Proper geometric and topological organization of DNA is essential for all
      chromosomal processes. Two classes of proteins play major roles in organizing
      chromosomes: condensin complexes and type II topoisomerases. In Escherichia coli,
      MukB, a structural maintenance of chromosome-like component of the bacterial
      condensin, and topoisomerase IV (Topo IV), a type II topoisomerase that
      decatenates the newly replicated daughter chromosomes, are both essential for
      chromosome segregation in rapidly growing cells. However, little is known about
      the interplay between MukB and Topo IV. Here we demonstrate a physical and
      functional interaction between MukB and ParC, a subunit of Topo IV, in vitro. The
      site of MukB interaction was located on the C-terminal domain of ParC and a loss
      of-interaction mutant, ParC R705E R729A, was isolated. This variant retained full
      activity as a topoisomerase when reconstituted with ParE to form Topo IV. We show
      that MukB stimulates the superhelical DNA relaxation activity of wild-type Topo
      IV, but not that of Topo IV reconstituted with ParC R705E R729A.

PMID- 20696939
TI  - The evolution of electronic structure in few-layer graphene revealed by optical
      spectroscopy.
AB  - The massless Dirac spectrum of electrons in single-layer graphene has been
      thoroughly studied both theoretically and experimentally. Although a subject of
      considerable theoretical interest, experimental investigations of the richer
      electronic structure of few-layer graphene (FLG) have been limited. Here we
      examine FLG graphene crystals with Bernal stacking of layer thicknesses N =
      1,2,3,...8 prepared using the mechanical exfoliation technique. For each layer
      thickness N, infrared conductivity measurements over the spectral range of 0.2
      1.0 eV have been performed and reveal a distinctive band structure, with
      different conductivity peaks present below 0.5 eV and a relatively flat spectrum
      at higher photon energies. The principal transitions exhibit a systematic energy
      scaling behavior with N. These observations are explained within a unified zone
      folding scheme that generates the electronic states for all FLG materials from
      that of the bulk 3D graphite crystal through imposition of appropriate boundary
      conditions. Using the Kubo formula, we find that the complete infrared
      conductivity spectra for the different FLG crystals can be reproduced reasonably
      well within the framework a tight-binding model.

PMID- 20696940
TI  - Quantifying uncertainty in climate change science through empirical information
      theory.
AB  - Quantifying the uncertainty for the present climate and the predictions of
      climate change in the suite of imperfect Atmosphere Ocean Science (AOS) computer
      models is a central issue in climate change science. Here, a systematic approach
      to these issues with firm mathematical underpinning is developed through
      empirical information theory. An information metric to quantify AOS model errors
      in the climate is proposed here which incorporates both coarse-grained mean model
      errors as well as covariance ratios in a transformation invariant fashion. The
      subtle behavior of model errors with this information metric is quantified in an
      instructive statistically exactly solvable test model with direct relevance to
      climate change science including the prototype behavior of tracer gases such as
      CO(2). Formulas for identifying the most sensitive climate change directions
      using statistics of the present climate or an AOS model approximation are
      developed here; these formulas just involve finding the eigenvector associated
      with the largest eigenvalue of a quadratic form computed through suitable
      unperturbed climate statistics. These climate change concepts are illustrated on
      a statistically exactly solvable one-dimensional stochastic model with relevance
      for low frequency variability of the atmosphere. Viable algorithms for
      implementation of these concepts are discussed throughout the paper.

PMID- 20696941
TI  - Characterization of nanoparticle release from surface coatings by the simulation
      of a sanding process.
AB  - Nanoparticles are used in industrial and domestic applications to control
      customized product properties. But there are several uncertainties concerning
      possible hazard to health safety and environment. Hence, it is necessary to
      search for methods to analyze the particle release from typical application
      processes. Based on a survey of commercial sanding machines, the relevant sanding
      process parameters were employed for the design of a miniature sanding test setup
      in a particle-free environment for the quantification of the nanoparticle release
      into air from surface coatings. The released particles were moved by a defined
      airflow to a fast mobility particle sizer and other aerosol measurement equipment
      to enable the determination of released particle numbers additionally to the
      particle size distribution. First, results revealed a strong impact of the
      coating material on the swarf mass and the number of released particles.

PMID- 20696942
TI  - CCR7 impairs hematopoiesis after hematopoietic stem cell transplantation
      increasing susceptibility to invasive aspergillosis.
AB  - Hematopoietic stem cell transplantation (HSCT) is limited by patient
      susceptibility to opportunistic infections. One of the most devastating
      infections after HSCT is invasive aspergillosis (IA), a life-threatening disease
      caused by Aspergillus fumigatus. Transplantation of hematopoietic stem cells
      (HSCs) and myeloid progenitor cells (MPCs) has been shown to mediate protection
      against IA, but little is known about the factors that regulate HSC and MPC cell
      expansion after transplantation. Herein, we investigated the role of CCR7 in a
      murine model of IA after combined HSC and MPC transplantation into lethally
      irradiated wild-type (WT) mice. Nonirradiated CCR7(-/-) mice had expanded
      populations of HSCs in the bone marrow and spleen, compared with WT mice.
      Irradiated WT mice reconstituted with CCR7(-/-) HSCs and MPCs had increased
      survival, decreased fungal burden, and enhanced myeloid leukocyte numbers during
      IA, compared with WT controls. In addition, WT mice reconstituted with WT HSCs
      and MPCs and treated with anti-CCR7 exhibited accelerated myeloid cell expansion
      similar to that observed in CCR7(-/-)->WT chimeras. Thus, removal of the
      inhibitory effects of CCR7 through genetic alteration or ligand
      immunoneutralization enhanced myeloid reconstitution, thereby accelerating fungal
      clearance in a murine model of IA.

PMID- 20696943
TI  - von Willebrand factor self-association on platelet GpIbalpha under hydrodynamic
      shear: effect on shear-induced platelet activation.
AB  - The function of the mechanosensitive, multimeric blood protein von Willebrand
      factor (VWF) is dependent on its size. We tested the hypothesis that VWF may self
      associate on the platelet glycoprotein Ibalpha (GpIbalpha) receptor under
      hydrodynamic shear. Consistent with this proposition, whereas Alexa-488
      conjugated VWF (VWF-488) bound platelets at modest levels, addition of unlabeled
      VWF enhanced the extent of VWF-488 binding. Recombinant VWF lacking the A1-domain
      was conjugated with Alexa-488 to produce DeltaA1-488. Although DeltaA1-488 alone
      did not bind platelets under shear, this protein bound GpIbalpha on addition of
      either purified plasma VWF or recombinant full-length VWF. The extent of self
      association increased with applied shear stress more than ~ 60 to 70 dyne/cm(2).
      DeltaA1-488 bound platelets in the milieu of plasma. On application of fluid
      shear to whole blood, half of the activated platelets had DeltaA1-488 bound,
      suggesting that VWF self-association may be necessary for cell activation.
      Shearing platelets with 6-MUm beads bearing either immobilized VWF or anti
      GpIbalpha mAb resulted in cell activation at shear stress down to 2 to 5
      dyne/cm(2). Taken together, the data suggest that fluid shear in circulation can
      increase the effective size of VWF bound to platelet GpIbalpha via protein self
      association. This can trigger mechanotransduction and cell activation by
      enhancing the drag force applied on the cell-surface receptor.

PMID- 20696944
TI  - Expression patterns of NKG2A, KIR, and CD57 define a process of CD56dim NK-cell
      differentiation uncoupled from NK-cell education.
AB  - Natural killer (NK) cells are lymphocytes of the innate immune system that,
      following differentiation from CD56(bright) to CD56(dim) cells, have been thought
      to retain fixed functional and phenotypic properties throughout their lifespan.
      In contrast to this notion, we here show that CD56(dim) NK cells continue to
      differentiate. During this process, they lose expression of NKG2A, sequentially
      acquire inhibitory killer cell inhibitory immunoglobulin-like receptors and CD57,
      change their expression patterns of homing molecules, and display a gradual
      decline in proliferative capacity. All cellular intermediates of this process are
      represented in varying proportions at steady state and appear, over time, during
      the reconstitution of the immune system, as demonstrated in humanized mice and in
      patients undergoing hematopoietic stem cell transplantation. CD56(dim) NK-cell
      differentiation, and the associated functional imprint, occurs independently of
      NK-cell education by interactions with self-human leukocyte antigen class I
      ligands and is an essential part of the formation of human NK-cell repertoires.

PMID- 20696945
TI  - Functional characterization of a 13-bp deletion (c.-1522_-1510del13) in the
      promoter of the von Willebrand factor gene in type 1 von Willebrand disease.
AB  - We have studied the effect of a 13-bp deletion in the promoter of the von
      Willebrand factor (VWF) gene in a patient with type 1 von Willebrand disease. The
      index case has a VWF:Ag of 0.49 IU/mL and is heterozygous for the deletion. The
      deletion is located 48 bp 5' of the transcription start site, and in silico
      analysis, electrophoretic mobility shift assays, and chromatin
      immunoprecipitation studies all predict aberrant binding of Ets transcription
      factors to the site of the deletion. Transduction of reporter gene constructs
      into blood outgrowth endothelial cells showed a 50.5% reduction in expression
      with the mutant promoter (n = 16, P < .001). A similar 40% loss of
      transactivation was documented in transduced HepG2 cells. A similar marked
      reduction of transgene expression was shown in the livers of mice injected with
      the mutant promoter construct (n = 8, P = .003). Finally, in studies of BOEC
      mRNA, the index case showed a 4.6-fold reduction of expression of the VWF
      transcript associated with the deletion mutation. These studies show that the 13
      bp deletion mutation alters the binding of Ets (and possibly GATA) proteins to
      the VWF promoter and significantly reduces VWF expression, thus playing a central
      pathogenic role in the type 1 von Willebrand disease phenotype in the index case.

PMID- 20696946
TI  - Oncogenic JAK2V617F requires an intact SH2-like domain for constitutive
      activation and induction of a myeloproliferative disease in mice.
AB  - The oncogenic JAK2V617F mutation is found in myeloproliferative neoplasms (MPNs)
      and is believed to be critical for leukemogenesis. Here we show that JAK2V617F
      requires an intact SH2 domain for constitutive activation of downstream signaling
      pathways. In addition, there is a strict requirement of cytokine receptor
      expression for the activation of this oncogene. Further analysis showed that the
      SH2 domain mutation did not interfere with JAK2 membrane distribution. However,
      coimmunoprecipitated experiments revealed a role for the SH2 domain in the
      aggregation and cross-phosphorylation of JAK2V617F at the cell membrane. Forced
      overexpression of cytokine receptors could rescue the JAK2V617F SH2 mutant
      supporting a critical role of JAK2V617F abundance for constitutive activation.
      However, under physiologic cytokine receptor expression the SH2 domain is
      absolutely necessary for oncogenic JAK2V617F activation. This is demonstrated in
      a bone marrow transplantation model, in which an intact SH2 domain in JAK2V617F
      is required for the induction of an MPN-like disease. Thus, our results points to
      an indispensable role of the SH2 domain in JAK2V617F-induced MPNs.

PMID- 20696948
TI  - Medical devices and the FDA approval process: balancing safety and innovation;
      comment on "prevalence of fracture and fragment embolization of bard retrievable
      vena cava filters and clinical implications including cardiac perforation and
      tamponade".

PMID- 20696947
TI  - When Toll-like receptor and T-cell receptor signals collide: a mechanism for
      enhanced CD8 T-cell effector function.
AB  - Emerging reports reveal that activating Toll-like receptor-2 (TLR2)-MyD88 signals
      in CD8 T lymphocytes enhances cytokine production and cytotoxicity; however, the
      signaling pathway remains undefined. In the present study, we examined the
      physiologic significance and molecular mechanisms involved in this process. We
      found that TLR2 engagement on T-cell receptor transgenic CD8 OT-1 T cells
      increased T-bet transcription factor levels consequently, augmenting effector
      transcript and protein levels both in vivo and in vitro. In contrast, TLR2
      agonist did not costimulate TLR2(-/-)OT-1 or MyD88(-/-)OT-1 T cells. Elevated T
      bet levels in TLR2-MyD88-activated T cells was a consequence of increased
      biosynthesis resulting from the enhanced activation of the mammalian target of
      the rapamycin (mTOR) pathway. Inhibiting mTOR, Akt, or protein kinase C in T
      cells abolished the costimulatory effects of the TLR2 agonist. In vivo,
      activating TLR2-MyD88 signals in T cells increased effector-molecule levels and
      enhanced the clearance of Listeria monocytogenes-Ova. These results help define a
      signaling pathway linking the TLR-MyD88 and mTOR pathway in an Akt- and protein
      kinase C-dependent manner. These results highlight a critical role for MyD88
      signaling in T-cell activation and cytotoxicity. Furthermore, these findings
      offer the opportunity for improving the efficacy of vaccines and T cell-based
      immunotherapies by targeting TLR-MyD88 signaling within T cells.

PMID- 20696949
TI  - Prevalence of fracture and fragment embolization of Bard retrievable vena cava
      filters and clinical implications including cardiac perforation and tamponade.
AB  - BACKGROUND: Vena cava filters represent an alternative treatment option for
      patients with contraindications to anticoagulation, or they might serve as
      adjunctive treatment for continued emboli despite anticoagulation. The fracture
      of a filter strut with subsequent end-organ embolization is a rarely reported but
      potentially life-threatening occurrence. METHODS: We sought to determine the
      prevalence of fracture and embolization of the Bard Recovery (first generation)
      and the Bard G2 (second generation) vena cava filters. A retrospective, single
      center, cross-sectional study was conducted by evaluating all patients who
      received either a Bard Recovery or Bard G2 filter from April 2004 until January
      2009. A total of 189 patients had undergone implantation: 1 pregnant woman and 35
      patients who died were excluded from our study. In addition, 10 patients who had
      the filter removed were also excluded. Ultimately, 80 patients participated in
      the trial. Subjects underwent fluoroscopy to assess the filter's integrity.
      Embolized struts were localized by fluoroscopy. Echocardiography and cardiac
      computed tomography were performed in patients with fragment embolization to the
      heart. RESULTS: Thirteen of 80 patients had at least 1 strut fracture (16%). At
      least 1 strut in 7 of the 28 Bard Recovery filters fractured and embolized (25%).
      In 5 of these 7 cases, patients had at least 1 fragment embolize to the heart
      (71%). Three patients experienced life-threatening symptoms of ventricular
      tachycardia and/or tamponade, including 1 patient who experienced sudden death at
      home. Six of 52 Bard G2 filters fractured (12%). In 2 of these 6 cases, the
      patients had asymptomatic end-organ fragment embolization. CONCLUSION: The Bard
      Recovery and Bard G2 filters had high prevalences of fracture and embolization,
      with potentially life-threatening sequelae.

PMID- 20696950
TI  - Waist circumference and all-cause mortality in a large US cohort.
AB  - BACKGROUND: Waist circumference (WC), a measure of abdominal obesity, is
      associated with higher mortality independent of body mass index (BMI). Less is
      known about the association between WC and mortality within categories of BMI or
      for the very high levels of WC that are now common. METHODS: We examined the
      association between WC and mortality among 48,500 men and 56,343 women, 50 years
      or older, in the Cancer Prevention Study II Nutrition Cohort. A total of 9315 men
      and 5332 women died between 1997 and the end of follow-up in 2006. RESULTS: After
      adjustment for BMI and other risk factors, very high levels of WC were associated
      with an approximately 2-fold higher risk of mortality in men and women (among
      men, relative risk [RR]=2.02; 95% confidence interval [CI], 1.71-2.39 for
      WC>or=120 cm compared with <90 cm; among women, RR=2.36; 95% CI, 1.98-2.82 for
      WC>or=110 cm compared with <75 cm). The WC was positively associated with
      mortality within all categories of BMI. In men, a 10-cm increase in WC was
      associated with RRs of 1.16 (95% CI, 1.09-1.23), 1.18 (95% CI, 1.12-1.24), and
      1.21 (95% CI, 1.13-1.30) within normal (18.5 to <25), overweight (25 to <30), and
      obese (>or=30) BMI categories, respectively. In women, corresponding RRs were
      1.25 (95% CI, 1.18-1.32), 1.15 (95% CI, 1.08-1.22), and 1.13 (95% CI, 1.06-1.20).
      CONCLUSION: These results emphasize the importance of WC as a risk factor for
      mortality in older adults, regardless of BMI.

PMID- 20696951
TI  - Communication discrepancies between physicians and hospitalized patients.
AB  - BACKGROUND: Hospital surveys indicate lack of patient awareness of diagnoses and
      treatments, yet physicians report they effectively communicate with patients.
      Gaps in understanding and communication could result in decreased quality of
      care. We sought to assess patient knowledge and perspectives of inpatient care
      and determine differences from physician assessments. METHODS: Two validated
      questionnaires assessed the experiences of inpatients treated by house staff from
      October 10, 2008, through June 23, 2009. We surveyed corresponding internal
      medicine resident and attending physicians, asking them to report on their care
      of hospitalized patients and their understanding of their patients' perspectives
      on the care received. RESULTS: Eighty-nine patients and 43 physicians
      participated. Although 73% of patients thought there was 1 main physician, 18%
      correctly named that physician, compared with 67% of physicians who thought
      patients knew their names (P<.001). Most physicians (77%) believed patients knew
      their diagnosis; however, 57% of patients did (P<.001). A total of 58% of
      patients thought that physicians always explained things in a comprehensible way,
      compared with 21% of physicians who stated they always provided explanations of
      some kind (P<.001). Two-thirds of patients reported receiving a new medication in
      the hospital, yet 90% noted never being told of any adverse effects of these
      medications. Nearly all physicians (98%) stated that they at least sometimes
      discussed their patients' fears and anxieties, compared with 54% of patients who
      said their physicians never did this (P=.001). CONCLUSIONS: Significant
      differences exist between patients' and physicians' impressions about patient
      knowledge and inpatient care received. Steps to improve patient-physician
      communication should be identified and implemented.

PMID- 20696954
TI  - Decreasing out-of-pocket costs of antibiotics: the good, the bad, and the
      unknown.

PMID- 20696953
TI  - Ambulatory antibiotic use and prescription drug coverage in older adults.
AB  - BACKGROUND: Several studies have shown that use of medications to treat chronic
      conditions is highly sensitive to out-of-pocket price and influenced by changes
      in insurance coverage. Because antibiotics target infections and are used for a
      short period, one may expect antibiotic use to be less responsive to price.
      However, no studies have evaluated how antibiotic use changes with drug coverage.
      We evaluate changes in ambulatory oral antibiotic use after implementation of the
      Medicare drug benefit (Part D). METHODS: We conducted a comparison group analysis
      2 years before and after implementation of Part D using insurance claims data
      from a large Medicare Advantage plan (January 1, 2004, through December 31,
      2007). Outcomes included the likelihood of using any oral antibiotics and major
      antibiotic subclasses among 35 102 older adults and rates of antibiotic use among
      those with pneumonia and other acute respiratory tract infections. RESULTS:
      Overall antibiotic use increased most among those who did not previously have
      drug coverage (relative odds ratio [OR], 1.58; 95% confidence interval [CI], 1.36
      1.85). Use of the broad spectrum antibiotic subclasses of quinolones (OR, 1.70;
      95% CI, 1.35-2.15) and macrolides (1.59; 1.26-2.01) increased more than the use
      of other subclasses, especially for those with prior drug coverage. Rates of
      ambulatory antibiotic use associated with pneumonia increased (OR, 3.60; 95% CI,
      2.35-5.53) more than those associated with other acute respiratory tract
      infections (2.29; 1.85-2.83). CONCLUSIONS: Antibiotic use increased among older
      adults whose drug coverage improved after Part D implementation, with the largest
      increases for broad spectrum, newer, and more expensive antibiotics. Our study
      suggests reimbursement may play a role in addressing inappropriate antibiotic
      use.

PMID- 20696955
TI  - Evaluation of consumer medication information dispensed in retail pharmacies.
AB  - BACKGROUND: United States retail pharmacies are key sources of written consumer
      medication information (CMI) through leaflets dispensed with prescription drugs.
      The content and format of this CMI are unregulated. Public Law 104-180 stipulates
      that by 2006, 95% of prescriptions be accompanied by "useful" CMI. METHODS:
      Professional shoppers filled prescriptions for lisinopril and metformin in a
      national sample of 365 pharmacies. Dispensed CMI was evaluated according to
      explicit criteria (77 for lisinopril and 78 for metformin) adapted from Food and
      Drug Administration guidelines. RESULTS: Six percent of pharmacies did not
      provide any written CMI. A mean (SD) of 60.2% (20.7%) and 57.7% (20.1%) of the
      criteria for useful CMI were met for lisinopril and metformin prescriptions,
      respectively. Shortcomings concerned especially "directions about use" with means
      of 53.4% (95% confidence interval [CI], 51.4%-56.5%) and 45.6% (43.7%-47.6%), and
      "comprehensibility/legibility," with means of 43.8% (42.6%-44.9%) and 42.6%
      (41.1%-43.7%) for lisinopril and metformin, respectively. The CMI leaflets ranged
      from 33 to 2482 words, with more than 1000-word differences among those meeting
      higher than 80% of the content criteria, suggesting large variations in
      conciseness. Chain pharmacies had better adherence to content criteria than did
      independent stores, with mean differences of 22.1% (95% CI, 15.8%-28.4%) for
      lisinopril and 21.1% (95% CI, 14.9%-27.3%) for metformin. CONCLUSIONS: Although
      distribution through pharmacies seems effective, the content, format, reading
      level, and excessive length of CMI are disconcerting. Private sector initiatives
      to provide useful CMI have failed. Research is needed on effective information
      selection and presentation in terms of effects on comprehension, retention, and
      appropriate patient actions to derive optimal drug benefit.

PMID- 20696956
TI  - Impact of Medicare Part D on seniors' out-of-pocket expenditures on medications.
AB  - BACKGROUND: Medicare Part D, introduced in January 2006, was intended to decrease
      beneficiaries' out-of-pocket expenditures on medications. METHODS: We examined
      whether this policy was successful in achieving this goal, including effects on
      Medicare beneficiaries without previous drug coverage and those who previously
      received coverage through Medicaid, in a longitudinal study of out-of-pocket
      expenditures on medications in 1504 Medicare beneficiaries 65 years and older
      participating in the 2005 and 2006 waves of the Medical Expenditure Panel Survey.
      RESULTS: Mean annual out-of-pocket expenditures on medications decreased by 32%
      ($320; 95% confidence interval [CI], $250-$391), from $1011 to $691, in the year
      after Part D was implemented for all Medicare beneficiaries in the Medical
      Expenditure Panel Survey. Mean annual out-of-pocket expenditures on medications
      decreased by 49% ($748; 95% CI, $600-$897), from $1533 to $784, in beneficiaries
      without previous drug coverage who enrolled in a Part D plan. Beneficiaries who
      did not enroll experienced a mean reduction of 32% ($353; 95% CI, $188-$518),
      from $1116 to $763. Mean annual out-of-pocket expenditures on medications
      remained similar in dual Medicare and Medicaid beneficiaries. CONCLUSIONS: The
      introduction of Medicare Part D was associated with reductions in Medicare
      beneficiaries' out-of-pocket expenditures on medications, particularly in
      beneficiaries without previous drug coverage, and did not substantially change
      expenditures for Medicare beneficiaries who previously received pharmacy coverage
      through Medicaid. However, a question remains about whether the high public cost
      of providing pharmacy coverage through Medicare is worth the substantially lower
      financial benefit derived by beneficiaries.

PMID- 20696957
TI  - Preventing potentially inappropriate medication use in hospitalized older
      patients with a computerized provider order entry warning system.
AB  - BACKGROUND: Potentially inappropriate medication (PIM) use in hospitalized older
      patients is common. Our objective was to determine whether a computerized
      provider order entry (CPOE) drug warning system can decrease orders for PIMs in
      hospitalized older patients. METHODS: We used a prospective before-and-after
      design among patients 65 years or older admitted to a large, urban academic
      medical center in Boston, Massachusetts, from June 1, 2004, through November 29,
      2004 (for patients admitted before the warning system was added), and from March
      17, 2005, through August 30, 2008 (patients admitted after the warning system was
      added). We instituted a medication-specific warning system within CPOE that
      alerted ordering providers at the point of care when ordering a PIM and that
      advised alternative medication or dose reduction. The main outcome measure was
      the rate of orders for PIMs before and after the warning system was deployed.
      RESULTS: The mean (SE) rate of ordering medications that were not recommended
      dropped from 11.56 (0.36) to 9.94 (0.12) orders per day after the implementation
      of a CPOE warning system (difference, 1.62 [0.33]; P<.001), with no evidence that
      the effect waned over time. There were no appreciable changes in the rate of
      ordering medications for which only dose reduction was recommended or that were
      not targeted after CPOE implementation. These effects persisted in autoregressive
      models that accounted for secular trends and season (P<.001). CONCLUSION:
      Specific alerts embedded into a CPOE system, used in patients 65 years or older,
      can decrease the number of orders of PIMs quickly and specifically.

PMID- 20696958
TI  - Spectrum of cancer risk late after AIDS onset in the United States.
AB  - BACKGROUND: Persons living with AIDS today remain at elevated cancer risk. Highly
      active antiretroviral therapy (HAART), widely available since 1996, prolongs
      life, but immune function is not fully restored. We conducted this study to
      assess long-term cancer risk among persons with AIDS relative to the general
      population and the impact of HAART on cancer incidence. METHODS: Records of 263
      254 adults and adolescents with AIDS (1980-2004) from 15 US regions were matched
      to cancer registries to capture incident cancers during years 3 through 5 and 6
      through 10 after AIDS onset. Standardized incidence ratios (SIRs) were used to
      assess risks relative to the general population. Rate ratios (RRs) were used to
      compare cancer incidence before and after 1996 to assess the impact of
      availability of HAART. RESULTS: Risk was elevated for the 2 major AIDS-defining
      cancers: Kaposi sarcoma (SIRs, 5321 and 1347 in years 3-5 and 6-10, respectively)
      and non-Hodgkin lymphoma (SIRs, 32 and 15). Incidence of both malignancies
      declined in the HAART era (1996-2006). Risk was elevated for all non-AIDS
      defining cancers combined (SIRs, 1.7 and 1.6 in years 3-5 and 6-10, respectively)
      and for the following specific non-AIDS-defining cancers: Hodgkin lymphoma and
      cancers of the oral cavity and/or pharynx, tongue, anus, liver, larynx, lung
      and/or bronchus, and penis. Anal cancer incidence increased between 1990-1995 and
      1996-2006 (RR, 2.9; 95% confidence interval [CI], 2.1-4.0), as did that of
      Hodgkin lymphoma (RR, 2.0; 95% CI, 1.3-2.9). CONCLUSION: Among people who
      survived for several years or more after an AIDS diagnosis, we observed high
      risks of AIDS-defining cancers and increasing incidence of anal cancer and
      Hodgkin lymphoma.

PMID- 20696959
TI  - An appraisal of non-AIDS-defining cancers: comment on "Spectrum of cancer risk
      late after AIDS onset in the United States".

PMID- 20696961
TI  - "A bird in the hand...": a commentary on the test and treat approach for HIV.

PMID- 20696960
TI  - Comparative effectiveness of HIV testing and treatment in highly endemic regions.
AB  - BACKGROUND: Universal testing and treatment holds promise for reducing the burden
      of human immunodeficiency virus (HIV) in sub-Saharan Africa, but linkage from
      testing to treatment sites and retention in care are inadequate. METHODS: We
      developed a simulation of the HIV epidemic and HIV disease progression in South
      Africa to compare the outcomes of the present HIV treatment campaign (status quo)
      with 4 HIV testing and treating strategies that increase access to antiretroviral
      therapy: (1) universal testing and treatment without changes in linkage to care
      and loss to follow-up; (2) universal testing and treatment with improved linkage
      to care; (3) universal testing and treatment with reduced loss to follow-up; and
      (4) comprehensive HIV care with universal testing and treatment, improved linkage
      to care, and reduced loss to follow-up. The main outcome measures were survival
      benefits, new HIV infections, and HIV prevalence. RESULTS: Compared with the
      status quo strategy, universal testing and treatment (1) was associated with a
      mean (95% uncertainty bounds) life expectancy gain of 12.0 months (11.3-12.2
      months), and 35.3% (32.7%-37.5%) fewer HIV infections over a 10-year time
      horizon. Improved linkage to care (2), prevention of loss to follow-up (3), and
      comprehensive HIV care (4) provided substantial additional benefits: life
      expectancy gains compared with the status quo strategy were 16.1, 18.6, and 22.2
      months, and new infections were 55.5%, 51.4%, and 73.2% lower, respectively. In
      sensitivity analysis, comprehensive HIV care reduced new infections by 69.7% to
      76.7% under a broad set of assumptions. CONCLUSIONS: Universal testing and
      treatment with current levels of linkage to care and loss to follow-up could
      substantially reduce the HIV death toll and new HIV infections. However,
      increasing linkage to care and preventing loss to follow-up provides nearly twice
      the benefits of universal testing and treatment alone.

PMID- 20696962
TI  - Gout, allopurinol use, and heart failure outcomes.
AB  - BACKGROUND: Hyperuricemia is associated with reduced survival among patients with
      heart failure (HF), but the effect of gout on HF outcomes is unknown. A recent
      randomized trial suggested that allopurinol may reduce adverse outcomes among
      patients with hyperuricemia and HF. Our objective was to determine whether gout
      and allopurinol use are associated with HF outcomes. METHODS: Time-matched,
      nested case-control analysis of a retrospective cohort of patients with HF who
      were 66 years or older using health care databases in Quebec, Canada. The primary
      outcome measure was a composite measure of HF readmission and all-cause
      mortality. The secondary outcome measure was all-cause mortality. Rate ratios
      were calculated using conditional logistic regression and adjusted for known
      prognostic factors. RESULTS: Of the 25,090 patients in this cohort, 14,327
      experienced the primary outcome. Both a remote history of gout and an acute
      episode of gout (within 60 days of the event date) were associated with an
      increased risk of HF readmission or death (adjusted rate ratio, 1.63; 95%
      confidence interval, 1.48-1.80; P<.001 and 2.06; 1.39-3.06; P<.001,
      respectively). Continuous allopurinol use (>30 days of continuous use) was not
      associated with the primary outcome among the overall population with HF
      (adjusted rate ratio, 1.02; 95% confidence interval, 0.95-1.10; P=.55) but was
      associated with reduced HF readmissions or death (0.69; 0.60-0.79; P<.001) and
      all-cause mortality (0.74; 0.61-0.90; P<.001) among patients with a history of
      gout. CONCLUSIONS: Patients with HF and a history of gout represent a high-risk
      population. Among such patients, the use of allopurinol is associated with
      improved outcomes.

PMID- 20696963
TI  - Outcomes and processes of care related to preoperative medical consultation.
AB  - BACKGROUND: Preoperative consultations by internal medicine physicians facilitate
      documentation of comorbid disease, optimization of medical conditions, risk
      stratification, and initiation of interventions intended to reduce risk.
      Nonetheless, the impact of these consultations, which may be performed by general
      internists or specialists, on outcomes is unclear. METHODS: We used population
      based administrative databases to conduct a cohort study of patients 40 years or
      older who underwent major elective noncardiac surgery in Ontario, Canada, between
      1994 and 2004. Propensity scores were used to assemble a matched-pairs cohort
      that reduced differences between patients who did and did not undergo
      preoperative consultation by general internists or specialists. The association
      of consultation with mortality and hospital stay was determined within this
      matched cohort. As a sensitivity analysis, we evaluated the association of
      consultation with an outcome for which no difference would be expected:
      postoperative wound infection. RESULTS: Of 269,866 patients in the cohort, 38.8%
      (n=104,695) underwent consultation. Within the matched cohort (n=191,852),
      consultation was associated with increased 30-day mortality (relative risk [RR],
      1.16; 95% confidence interval [CI], 1.07-1.25; number needed to harm, 516), 1
      year mortality (1.08; 1.04-1.12; number needed to harm, 227), mean hospital stay
      (difference, 0.67 days; 0.59-0.76), preoperative testing, and preoperative
      pharmacologic interventions. Notably, consultation was not associated with any
      difference in postoperative wound infections (RR, 0.98; 95% CI, 0.95-1.02). These
      findings were stable across subgroups as well as sensitivity analyses that tested
      for unmeasured confounding. CONCLUSIONS: Medical consultation before major
      elective noncardiac surgery is associated with increased mortality and hospital
      stay, as well as increases in preoperative pharmacologic interventions and
      testing. These findings highlight the need to better understand mechanisms by
      which consultation influences outcomes and to identify efficacious interventions
      to decrease perioperative risk.

PMID- 20696964
TI  - Medication in relation to ST-segment elevation myocardial infarction in patients
      with a first myocardial infarction: Swedish Register of Information and Knowledge
      About Swedish Heart Intensive Care Admissions (RIKS-HIA).
AB  - BACKGROUND: The extent and the severity of acute myocardial infarction (MI) is
      decreasing. Out-of-hospital medical management before the hospital admission
      could alter clinical presentation in acute MI. We used a large national patient
      register to investigate the relation between previous medication use (aspirin,
      beta-blockers, angiotensin-converting enzyme [ACE] inhibitors, and statins) and
      the risk of presenting with ST-segment elevation MI (STEMI) or non-STEMI.
      METHODS: We included 103 459 consecutive patients from the Swedish Register of
      Information and Knowledge About Swedish Heart Intensive Care Admissions (RIKS
      HIA) admitted between January 1, 1996, and December 31, 2006, with a first acute
      MI. RESULTS: The patients with STEMI (43.5% of the total) were younger, had less
      prior cardiovascular disease, and used fewer medications before hospitalization.
      Of the STEMI patients, 61.4% had used no medication vs 45.9% of the patients with
      non-STEMI. After multiple adjustments, use of aspirin, beta-blockers, ACE
      inhibitors, and statins before hospitalization were all associated with
      substantially lower odds of presenting with STEMI. Furthermore, the risk
      decreased with the number of previous medications, and the use of 3 or more
      medications was associated with a multiply adjusted odds ratio of presenting with
      STEMI of 0.48 (99% confidence interval, 0.44-0.52) compared with no medications
      at admission. CONCLUSIONS: Use of aspirin, beta-blockers, ACE inhibitors, or
      statins before hospital admission in patients with a first acute MI is associated
      with substantially less risk of presenting with STEMI. The risk decreases with
      the increasing number of these medications used before acute MI, underlining the
      benefit of preventive medication in high-risk patients.

PMID- 20696965
TI  - Primary prevention of myocardial infarction: putting the evidence to use.

PMID- 20696967
TI  - Impact of biochemical recurrence in prostate cancer among US veterans.
AB  - BACKGROUND: Among men treated for prostate cancer, increasing prostate-specific
      antigen (PSA) is known as biochemical failure or biochemical recurrence (BCR).
      The impact of BCR on subsequent mortality is uncertain, however, especially given
      competing causes of death. METHODS: To describe patterns of BCR and subsequent
      mortality, we conducted an observational study in a community-based, "high
      comorbidity" setting of 623 US veterans diagnosed as having prostate cancer from
      1991 to 1995 and receiving radical prostatectomy or radiation therapy. The main
      outcome measures were BCR, defined as a PSA level of 0.4 ng/mL or higher (treated
      with surgery) or "PSA nadir+2 ng/mL" (treated with radiation therapy), and
      prostate cancer mortality, determined through 2006. RESULTS: With 5-, 10-, and 15
      year follow-up periods, respectively (for all results shown herein), the
      cumulative incidence of BCR after prostatectomy (n=225) was 34%, 37%, and 37%;
      prostate cancer mortality among men who failed treatment (n=81) was 3%, 11%, and
      21%. Among men receiving radiation therapy (n=398), the cumulative incidence of
      BCR was 35%, 46%, and 48%; prostate cancer mortality among those who failed
      treatment (n=161) was 11%, 20%, and 42%. Overall, BCR was associated with an
      increased risk of death from prostate cancer in the study population, but the
      individual probability of this outcome was relatively low. CONCLUSIONS:
      Biochemical recurrence is associated with increased prostate cancer mortality,
      yet when BCR occurs only a minority of men subsequently die of their disease. The
      phrase "most men die with prostate cancer, not of it" applies to elderly
      veterans, even after failure of primary treatment. New strategies for defining
      and managing treatment failure in prostate cancer are needed.

PMID- 20696966
TI  - Simplification of the pulmonary embolism severity index for prognostication in
      patients with acute symptomatic pulmonary embolism.
AB  - BACKGROUND: The Pulmonary Embolism Severity Index (PESI) estimates the risk of 30
      day mortality in patients with acute pulmonary embolism (PE). We constructed a
      simplified version of the PESI. METHODS: The study retrospectively developed a
      simplified PESI clinical prediction rule for estimating the risk of 30-day
      mortality in a derivation cohort of Spanish outpatients. Simplified and original
      PESI performances were compared in the derivation cohort. The simplified PESI
      underwent retrospective external validation in an independent multinational
      cohort (Registro Informatizado de la Enfermedad Tromboembolica [RIETE] cohort) of
      outpatients. RESULTS: In the derivation data set, univariate logistic regression
      of the original 11 PESI variables led to the removal of variables that did not
      reach statistical significance and subsequently produced the simplified PESI that
      contained the variables of age, cancer, chronic cardiopulmonary disease, heart
      rate, systolic blood pressure, and oxyhemoglobin saturation levels. The
      prognostic accuracy of the original and simplified PESI scores did not differ
      (area under the curve, 0.75 [95% confidence interval (CI), 0.69-0.80]). The 305
      of 995 patients (30.7%) who were classified as low risk by the simplified PESI
      had a 30-day mortality of 1.0% (95% CI, 0.0%-2.1%) compared with 10.9% (8.5%
      13.2%) in the high-risk group. In the RIETE validation cohort, 2569 of 7106
      patients (36.2%) who were classified as low risk by the simplified PESI had a 30
      day mortality of 1.1% (95% CI, 0.7%-1.5%) compared with 8.9% (8.1%-9.8%) in the
      high-risk group. CONCLUSION: The simplified PESI has similar prognostic accuracy
      and clinical utility and greater ease of use compared with the original PESI.

PMID- 20696968
TI  - Severity of comorbidity and non-prostate cancer mortality in men with early-stage
      prostate cancer.

PMID- 20696969
TI  - Invited commentary: Prostate cancer: doing less might be more. Comment on
      "Severity of comorbidity and non-prostate cancer mortality in men with early
      stage prostate cancer".

PMID- 20696970
TI  - Lack of improvement in outpatient management of congestive heart failure in the
      United States.

PMID- 20696971
TI  - Coffee intake and glucose homeostasis: is there a role for body iron?

PMID- 20696972
TI  - Predictors of flight diversions and deaths for in-flight medical emergencies in
      commercial aviation.

PMID- 20696973
TI  - Effect of Enzyte on QT and QTc intervals.

PMID- 20696974
TI  - Invited commentary: The safety of dietary supplements. Comment on "Effect of
      Enzyte on QT and Qtc intervals".

PMID- 20696975
TI  - Nursing home culture discourages physician involvement.

PMID- 20696976
TI  - The physician's role in nursing homes: the Dutch solution.

PMID- 20696977
TI  - Does methadone prolong QTc intervals by depleting testosterone levels?

PMID- 20696978
TI  - Trends in population burden of COPD: actual facts or fallacies?

PMID- 20696980
TI  - Monitoring adherence to medication by measuring change in blood pressure.
AB  - After starting antihypertensives, blood pressure is monitored for several
      reasons, including assessment of adherence. We aimed to estimate the accuracy of
      blood pressure monitoring for detecting early nonadherence. We conducted a
      secondary analysis of the Perindopril Protection Against Recurrent Stroke Study
      (PROGRESS), a large randomized trial of blood pressure lowering to reduce the
      risk of recurrent stroke. We compared change in blood pressure 3 months after
      randomization in people who had discontinued treatment (nonadherent) with those
      who stayed on treatment (adherent). We also used an indirect method, assessing
      whether change in blood pressure discriminated between active (adherent) and
      placebo (nonadherent) groups. Both methods gave similar results. For the 3433
      subjects, the mean (SD) of the change in systolic blood pressure was -15.8 mm Hg
      (SD 18.7 mm Hg) in the adherent group and -4.2 mm Hg (SD 18.1 mm Hg) in the
      nonadherent group. After recalibration of the mean change in the nonadherent
      group to 0 mm Hg and in the adherent group to -11.6 mm Hg, the absence of a fall
      in systolic blood pressure at 3 months had a sensitivity of 50% and a specificity
      of 80% for detecting nonadherence (50% of nonadherent patients and 20% of
      adherent patients had a rise in blood pressure). Discriminatory power was modest
      over the range of cutoffs (area under the receiver-operator curve 0.67).
      Monitoring blood pressure is poor at detecting nonadherence to blood pressure
      lowering treatment. Further research should look at other methods of assessing
      adherence.

PMID- 20696979
TI  - Canadian Glaucoma Study: 3. Impact of risk factors and intraocular pressure
      reduction on the rates of visual field change.
AB  - OBJECTIVES: To determine rates of visual field change associated with risk
      factors for progression in the Canadian Glaucoma Study (abnormal anticardiolipin
      antibody level, age, female sex, and mean follow-up intraocular pressure [IOP]),
      and to evaluate the effect of IOP reduction on subsequent rates of visual field
      change in progressing patients. METHODS: Two hundred sixteen patients (median
      age, 65.2 years) were followed up at 4-month intervals with perimetry and were
      monitored for progression. Patients reaching an end point based on total
      deviation analysis underwent 20% or greater reduction in IOP. Rates of mean
      deviation (MD) change were calculated. RESULTS: Patients with 0, 1, and 2 end
      points had a median of 18, 23, and 25 examinations, respectively. The median MD
      rate in progressing patients prior to the first end point was significantly worse
      compared with those with no progression (-0.35 and 0.05 dB/y, respectively). An
      abnormal anticardiolipin antibody level was associated with a significantly worse
      MD rate compared with a normal anticardiolipin antibody level (-0.57 and -0.03
      dB/y, respectively). Increasing age was associated with a worse MD rate, but
      female sex and mean follow-up IOP were not. After the first end point, the median
      IOP decreased from 18.0 to 14.8 mm Hg (20% in individual patients), resulting in
      a significant MD rate change from -0.36 to -0.11 dB/y. CONCLUSIONS: Patients with
      abnormal anticardiolipin antibody levels and increasing age had faster visual
      field change. Modest IOP reduction in progressing patients significantly
      ameliorated the rate of visual field decline. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT00262626.

PMID- 20696981
TI  - Angiotensin II enhances connecting tubule glomerular feedback.
AB  - Increasing Na delivery to epithelial Na channels (ENaCs) in the connecting tubule
      (CNT) causes dilation of the afferent arteriole (Af-Art), a process we call CNT
      glomerular feedback (CTGF). Angiotensin II (Ang II) stimulates ENaC in the
      collecting duct via Ang II type 1 receptors. We hypothesized that Ang II in the
      CNT lumen enhances CTGF by activation of Ang II type 1 receptors, protein kinase
      C and ENaC. Rabbit afferent arterioles and their adherent CNT were microperfused
      and preconstricted with norepinephrine. Each experiment involved generating 2
      consecutive concentration-response curves by increasing NaCl in the CNT lumen.
      During the control period, the maximum dilation of the afferent arteriole was
      7.9+/-0.4 MUm, and the concentration of NaCl in the CNT needed to achieve half
      maximal response (EC(50)) was 34.7+/-5.2 mmol/L. After adding Ang II (10(-9)
      mol/L) to the CNT lumen, the maximal response was 9.5+/-0.7 MUm and the EC(50)
      was 11.6+/-1.3 mmol/L (P=0.01 versus control). Losartan, an Ang II type 1
      antagonist (10(-6) mol/L) blocked the stimulatory effect of Ang II; PD123319, an
      Ang II type 2 antagonist (10(-6) mol/L), did not. The protein kinase C inhibitor
      staurosporine (10(-8) mol/L) added to the CNT inhibited the stimulatory effect of
      Ang II. The ENaC inhibitor benzamil (10(-6) mol/L) prevented both CTGF and its
      stimulation by Ang II. We concluded that Ang II in the CNT lumen enhances CTGF
      via activation of Ang II type 1 and that this effect requires activation of
      protein kinase C and ENaC. Potentiation of CTGF by Ang II could help preserve
      glomerular filtration rate in the presence of renal vasoconstriction.

PMID- 20696982
TI  - Angiotensin II and NADPH oxidase increase ADMA in vascular smooth muscle cells.
AB  - Asymmetrical dimethylarginine inhibits nitric oxide synthase, cationic amino acid
      transport, and endothelial function. Patients with cardiovascular risk factors
      often have endothelial dysfunction associated with increased plasma asymmetrical
      dimethylarginine and markers of reactive oxygen species. We tested the hypothesis
      that reactive oxygen species, generated by nicotinamide adenine dinucleotide
      phosphate oxidase, enhance cellular asymmetrical dimethylarginine. Incubation of
      rat preglomerular vascular smooth muscle cells with angiotensin II doubled the
      activity of nicotinamide adenine dinucleotide phosphate oxidase but decreased the
      activities of dimethylarginine dimethylaminohydrolase by 35% and of cationic
      amino acid transport by 20% and doubled cellular (but not medium) asymmetrical
      dimethylarginine concentrations (P<0.01). This was blocked by tempol or
      candesartan. Cells stably transfected with p22(phox) had a 50% decreased protein
      expression and activity of dimethylarginine dimethylaminohydrolase despite
      increased promoter activity and mRNA. The decreased DDAH protein expression and
      the increased asymmetrical dimethylarginine concentration in p22(phox)
      transfected cells were prevented by proteosomal inhibition. These cells had
      enhanced protein arginine methylation, a 2-fold increased expression of protein
      arginine methyltransferase-3 (P<0.05) and a 30% reduction in cationic amino acid
      transport activity (P<0.05). Asymmetrical dimethylarginine was increased from 6+/
      1 to 16+/-3 micromol/L (P<0.005) in p22(phox)-transfected cells. Thus,
      angiotensin II increased cellular asymmetrical dimethylarginine via type 1
      receptors and reactive oxygen species. Nicotinamide adenine dinucleotide
      phosphate oxidase increased cellular asymmetrical dimethylarginine by increasing
      enzymes that generate it, enhancing the degradation of enzymes that metabolize
      it, and reducing its cellular transport. This could underlie increases in
      cellular asymmetrical dimethylarginine during oxidative stress.

PMID- 20696983
TI  - Vascular smooth muscle cell differentiation to an osteogenic phenotype involves
      TRPM7 modulation by magnesium.
AB  - Arterial calcification, common in vascular diseases, involves vascular smooth
      muscle cell (VSMC) transformation to an osteoblast phenotype. Clinical studies
      suggest that magnesium may prevent this, but mechanisms are unclear. We assessed
      whether increasing magnesium levels reduce VSMC calcification and differentiation
      and questioned the role of the Mg(2+) transporter, transient receptor potential
      melastatin (TRPM)7 cation channels in this process. Rat VSMCs were exposed to
      calcification medium in the absence and presence of magnesium (2.0 to 3.0 mmol/L)
      or 2-aminoethoxy-diphenylborate (2-APB) (TRPM7 inhibitor). VSMCs from mice with
      genetically low (MgL) or high-normal (MgH) [Mg(2+)](i) were also studied.
      Calcification was assessed by von Kossa staining. Expression of osteocalcin,
      osteopontin, bone morphogenetic protein (BMP)-2, BMP-4, BMP-7, and matrix Gla
      protein and activity of TRPM7 (cytosol:membrane translocation) were determined by
      immunoblotting. Calcification medium induced osteogenic differentiation, reduced
      matrix Gla protein content, and increased expression of the sodium-dependent
      cotransporter Pit-1. Magnesium prevented calcification and decreased osteocalcin
      expression and BMP-2 activity and increased expression of calcification
      inhibitors, osteopontin and matrix Gla protein. TRPM 7 activation was decreased
      by calcification medium, an effect reversed by magnesium. 2-APB recapitulated the
      VSMC osteoblastic phenotype in VSMCs. Osteocalcin was increased by calcification
      medium in VSMCs and intact vessels from MgL but not MgH, whereas osteopontin was
      increased in MgH, but not in MgL mice. Magnesium negatively regulates vascular
      calcification and osteogenic differentiation through increased/restored TRPM7
      activity and increased expression of anticalcification proteins, including
      osteopontin, BMP-7, and matrix Gla protein. New molecular insights are provided
      whereby magnesium could protect against VSMC calcification.

PMID- 20696984
TI  - Moment-to-moment characteristics of the relationship between arterial pressure
      and renal interstitial hydrostatic pressure.
AB  - The kidney is a key controller of the long-term level of arterial pressure, in
      part through pressure-natriuresis. Although direct coupling of changes in renal
      arterial pressure to renal interstitial hydrostatic pressure (RIHP) and
      consequent sodium excretion is well established, few studies have characterized
      the moment-to-moment aspects of this process. These studies characterized the
      short-term hemodynamic component of pressure-natriuresis in vivo before and after
      autonomic nervous system and renin-angiotensin system inhibition. Changes in RIHP
      were determined over a range of renal arterial pressures in Wistar rats receiving
      no treatment, a ganglionic blocker (hexamethonium; 20 mg/kg per hour IV), or an
      angiotensin II type 1 receptor blocker (losartan; 10 mg/kg per hour IV). After a
      series of changes in renal arterial pressure, a delay of only ~1 second was found
      for the onset of RIHP responses that was independent of the stimulus magnitude
      and neurohumoral manipulation; however, completion of the full RIHP response was
      within ~15 seconds for renal arterial pressure changes of <=30 mm Hg. The overall
      slope of the renal arterial pressure- RIHP relationship (0.09+/-0.01) was also
      not affected by autonomic nervous system and renin-angiotensin system inhibition
      despite decreasing renal arterial pressure (?40% and ?28%, respectively).
      Separate assessment of this relationship above and below the prevailing arterial
      pressure revealed that the pressor versus the depressor portion was blunted
      (P<0.001), a difference that was abolished after autonomic nervous system and
      renin-angiotensin system inhibition. The results suggest that spontaneous changes
      in arterial pressure are coupled to moment-to-moment changes in RIHP over a wide
      range of pressures, emphasizing a likely role for the dynamic component of the
      renal arterial pressure-RIHP relationship in the modulation of sodium excretion
      and, hence, arterial pressure.

PMID- 20696986
TI  - Reduction of myeloperoxidase activity by melatonin and pycnogenol may contribute
      to their blood pressure lowering effect.

PMID- 20696985
TI  - Role of phosphoinositide 3-kinase {alpha}, protein kinase C, and L-type Ca2+
      channels in mediating the complex actions of angiotensin II on mouse cardiac
      contractility.
AB  - Although angiotensin II (Ang II) plays an important role in heart disease
      associated with pump dysfunction, its direct effects on cardiac pump function
      remain controversial. We found that after Ang II infusion, the developed pressure
      and +dP/dt(max) in isolated Langendorff-perfused mouse hearts showed a complex
      temporal response, with a rapid transient decrease followed by an increase above
      baseline. Similar time-dependent changes in cell shortening and L-type Ca(2+)
      currents were observed in isolated ventricular myocytes. Previous studies have
      established that Ang II signaling involves phosphoinositide 3-kinases (PI3K).
      Dominant-negative inhibition of PI3Kalpha in the myocardium selectively
      eliminated the rapid negative inotropic action of Ang II (inhibited by
      approximately 90%), whereas the loss of PI3Kgamma had no effect on the response
      to Ang II. Consistent with a link between PI3Kalpha and protein kinase C (PKC),
      PKC inhibition (with GF 109203X) reduced the negative inotropic effects of Ang II
      by approximately 50%. Although PI3Kalpha and PKC activities are associated with
      glycogen synthase kinase-3beta and NADPH oxidase, genetic ablation of either
      glycogen synthase kinase-3beta or p47(phox) (an essential subunit of NOX2-NADPH
      oxidase) had no effect on the inotropic actions of Ang II. Our results establish
      that Ang II has complex temporal effects on contractility and L-type Ca(2+)
      channels in normal mouse myocardium, with the negative inotropic effects
      requiring PI3Kalpha and PKC activities.

PMID- 20696987
TI  - Control rates of hypertension in North America.

PMID- 20696988
TI  - Tumor necrosis factor-alpha antagonist etanercept decreases blood pressure and
      protects the kidney in a mouse model of systemic lupus erythematosus.
AB  - Chronic inflammation has been implicated in the pathology of hypertension;
      however, the role for specific cytokines remains unclear. We tested whether tumor
      necrosis factor-alpha blockade with etanercept (Etan) reduces mean arterial
      pressure in a female mouse model of systemic lupus erythematosus (SLE). SLE is a
      chronic inflammatory disorder with prevalent hypertension. Thirty-week-old SLE
      (NZBWF1) and control mice (NZW/LacJ) received Etan (0.8 mg/kg SC weekly) for 4
      weeks or vehicle. Mean arterial pressure (in millimeters of mercury) was
      increased in SLE mice (150+/-5 versus 113+/-5 in controls; P<0.05) and was lower
      in Etan-treated SLE mice (132+/-3) but not controls (117+/-5). Albuminuria (in
      micrograms per milligram of creatinine) was elevated in SLE mice (28 742+/-9032
      versus 1075+/-883; P<0.05) and was lower in Etan-treated SLE mice (8154+/-3899)
      but not control animals (783+/-226). Glomerulosclerosis (in percentage of
      glomeruli) was evident in SLE mice (2.5+/-1.6 versus 0.0+/-0.0 in controls;
      P<0.05) and was ameliorated in Etan-treated SLE mice (0.1+/-0.1). Renal cortex
      CD68(+) cell staining (in percentage of area) was elevated in SLE mice (4.75+/
      0.80 versus 0.79+/-0.12 in controls; P<0.05) and was lower in Etan-treated SLE
      mice (2.28+/-0.32) but not controls (1.43+/-0.25). Renal cortex NADPH oxidase
      activity (relative light units per milligram of protein) was higher in SLE mice
      compared with controls (10 718+/-1276 versus 7584+/-229; P<0.05) and lowered in
      Etan-treated SLE mice (6645+/-490). Renal cortex nuclear factor kappaB
      (phosphorylated and nonphosphorylated) was increased in SLE mice compared with
      controls and lower in Etan-treated SLE mice. These data suggest that TNF-alpha
      mechanistically contributes to the development of hypertension in a chronic
      inflammatory disease through increased renal nuclear factor kappaB, oxidative
      stress, and inflammation.

PMID- 20696989
TI  - The impact of cardiovascular risk factors on aortic stiffness and wave
      reflections depends on age: the Anglo-Cardiff Collaborative Trial (ACCT III).
AB  - Ageing exerts differential effects on arterial stiffness and wave reflections.
      However, the impact of cardiovascular risk factors on arterial stiffness and wave
      reflections and, particularly, how such effects are influenced by ageing has not
      been assessed within a single large population, covering a sufficiently wide age
      range. Therefore, we determined the extent to which age alters the impact of
      traditional cardiovascular risk factors on arterial stiffness and wave
      reflections. Aortic stiffness and wave reflections were assessed in 4421
      individuals (age range 18 to 92 years). When treated as continuous variables,
      clinic systolic, diastolic, and pulse pressures and glucose levels were
      independently associated with stiffness, and, with the exception of diastolic
      pressure, these associations were more marked in older individuals. In contrast,
      clinic systolic and diastolic pressures and smoking were independently associated
      with wave reflections, with stronger associations observed in younger
      individuals. The impact of traditional cardiovascular risk factors on arterial
      stiffness and wave reflections is strongly dependent on age and is largely driven
      by blood pressure. Additional studies are required to assess the impact of these
      arterial measures on cardiovascular outcome within a single population.

PMID- 20696990
TI  - Hyperaldosteronism and left ventricular hypertrophy.

PMID- 20696991
TI  - Negative inotropy by angiotensin II is mediated via phosphoinositide 3-kinase
      alpha-protein kinase C-coupled signaling pathway.

PMID- 20696992
TI  - Angiopoietin-1 induces migration of monocytes in a tie-2 and integrin-independent
      manner.
AB  - Angiopoietin-1 (Ang-1) is an angiogenic growth factor that activates Tie-2 and
      integrins to promote vessel wall remodeling. The recent finding of the potential
      proatherogenic effects of Ang-1 prompted us to investigate whether Ang-1 promotes
      monocyte chemotaxis, endothelial binding, and transendothelial migration, key
      events in the progression of atherosclerosis. Here, we show that Ang-1 induces
      chemotaxis of monocytes in a manner that is independent of Tie-2 and integrin
      binding but dependent on phosphoinositide 3-kinase and heparin. In addition, Ang
      1 promoted phosphoinositide 3-kinase-dependent binding of monocytes to
      endothelial monolayers and stimulated transendothelial migration. Fluorescence
      activated cell sorting analysis showed that exogenous Ang-1 adheres directly to
      monocytes as well as to human umbilical endothelial cells, but neither Tie-2 mRNA
      nor protein were expressed by primary monocytes. Although Ang-1 binding to human
      umbilical endothelial cells was partially Tie-2 and integrin dependent, Ang-1
      binding to monocytes was independent of these factors. Finally, preincubation of
      monocytes with soluble heparin abrogated Ang-1 binding to monocytes and
      migration, and partially prevented Ang-1 binding to human umbilical endothelial
      cells. In summary, Ang-1 induces chemotaxis of monocytes by a mechanism that is
      dependent on phosphoinositide 3-kinase and heparin but independent of Tie-2 and
      integrins. The ability of Ang-1 to recruit monocytes suggests it may play a role
      in inflammatory angiogenesis and may promote atherosclerosis.

PMID- 20696993
TI  - Aldosterone, plasma Renin activity, and aldosterone/renin ratio in a normotensive
      healthy pediatric population.
AB  - Primary aldosteronism is an important cause of secondary hypertension and is
      suspected in adults with an aldosterone/renin ratio > or =25. The normal
      aldosterone/renin ratio is unknown in children. The aim was to establish serum
      aldosterone, plasma renin activity, and aldosterone/renin ratio values in a
      healthy pediatric population. A cross-sectional study was performed in 211
      healthy normotensive children (4 to 16 years old). Two subgroups of normotensive
      children were obtained: with hypertensive parents (NH) (n=113) and normotensive
      parents (n=98). Blood samples for measuring serum aldosterone, plasma renin
      activity, aldosterone/renin ratio, and DNA were collected. In subjects with
      aldosterone/renin ratio > or =25, the chimeric CYP11B1/CYP11B2 gene was
      investigated by long-extension PCR. Results are expressed as median [Q(1)-Q(3)].
      NH and normotensive parents groups were similar in serum aldosterone (6.5 [3.6 to
      9.0] ng/dL versus 6.5 [2.9 to 9.7] ng/dL; P=0.968) and plasma renin activity (2.3
      [1.6 to 3.1] versus 2.4 [1.7 to 3.7] ng/mL per hour; P=0.129). The
      aldosterone/renin ratio was higher in the NH group, but this difference did not
      reach statistical significance (2.8 [1.9 to 4.1] versus 2.5 [1.4 to 4.0],
      P=0.104). In one subject of the NH group, the chimeric CYP11B1/CYP11B2 gene was
      detected. We demonstrated that normal aldosterone/renin ratio values in a healthy
      pediatric population without NH were lower than those reported for an adult
      normotensive population.

PMID- 20696994
TI  - Calorie restriction prevents hypertension and cardiac hypertrophy in the
      spontaneously hypertensive rat.
AB  - Because recent evidence demonstrated that calorie restriction (CR) has numerous
      beneficial cardiovascular effects, we investigated whether short-term CR could
      reduce hypertension and prevent cardiac hypertrophy inherent to the nonobese
      spontaneously hypertensive rat (SHR). After 5 weeks of either ad libitum feeding
      or short-term CR, SHRs subjected to short-term CR had lower systolic blood
      pressure (BP) and reduced left ventricular wall thickness as assessed by
      noninvasive tail-cuff BP measurements and echocardiography, respectively. In
      addition, ultrasound measurements of the femoral artery revealed that flow
      mediated vasodilation was significantly improved in SHRs with CR compared to
      controls. Moreover, pressure myography of isolated mesenteric arteries and
      subsequent histological and biochemical analysis of these arteries demonstrated
      that short-term CR improved vascular compliance, increased endothelial nitric
      oxide synthase (eNOS) activity and nitric oxide bioavailability, and reduced
      vascular remodeling compared to ad libitum-fed SHRs. Although these effects are
      likely multifactorial, they were associated with elevated levels of the
      circulating adipokine, adiponectin, and enhanced AMP-activated protein kinase
      (AMPK) activity. To provide evidence that elevated adiponectin levels in the SHR
      is sufficient to prevent an increase in BP, adenoviral-mediated overexpression of
      adiponectin increased circulating levels of adiponectin, reduced BP, and
      activated the AMPK/eNOS pathway in the absence of CR. Overall, our findings
      provide compelling evidence that short-term CR exerts beneficial effects in the
      SHR via stimulation of an adiponectin/AMPK/eNOS signaling axis. As a result, CR
      may serve as an effective nonpharmacological treatment of hypertension, and
      targeting the adiponectin/AMPK/eNOS pathway may improve treatment of
      hypertension.

PMID- 20696995
TI  - Resident-performed phacoemulsification surgery in tamsulosin-treated patients.
AB  - OBJECTIVES: To compare intraoperative complication rates and visual outcomes for
      patients treated and not treated with tamsulosin hydrochloride who underwent
      resident-performed phacoemulsification, and to determine whether the recognition
      of intraoperative floppy iris syndrome in 2005 affected the subsequent
      complication rates for tamsulosin-treated patients. METHODS: This comparative
      retrospective cohort study included 101 tamsulosin-treated eyes and 404 non
      tamsulosin-treated eyes from January 1, 1998, to August 31, 2008. Main outcome
      measures were major and minor complication rates and postoperative best-corrected
      visual acuity. Complication rates were compared between August 11, 1999, to
      December 31, 2005, and January 1, 2006, to September 3, 2008, for both tamsulosin
      treated and non-tamsulosin-treated eyes. RESULTS: The major complication rates
      were 3.0% for tamsulosin-treated eyes and 8.9% for non-tamsulosin-treated eyes (P
      = .08), while the minor complication rates were 24.8% and 12.1%, respectively (P
      = .002). Both groups had an equal likelihood of attaining better than 20/40
      postoperative visual acuities (82.2% vs 82.9%, respectively; P = .85). Frequency
      of major complications between tamsulosin-treated and non-tamsulosin-treated eyes
      was 6.0% vs 15.8%, respectively (P = .09), from August 11, 1999, to December 31,
      2005, compared with 0.0% vs 2.0%, respectively (P > .99), from January 1, 2006,
      to September 3, 2008. CONCLUSIONS: Differences in the major complication rates
      for tamsulosin-treated and non-tamsulosin-treated eyes were not significant,
      whereas tamsulosin exposure was associated with a significant increase in minor
      complications. Both groups had similar, good postoperative visual outcomes. After
      2005, a reduction in major complications was seen in both groups, attributed to
      programmatic changes in surgical education. Recognition of intraoperative floppy
      iris syndrome did not impart a significant additional protective effect in
      preventing major complications.

PMID- 20696996
TI  - Clinicopathologic findings in failed descemet stripping automated endothelial
      keratoplasty.
AB  - OBJECTIVE: To evaluate the clinical features of and histologic findings from
      failed Descemet stripping automated endothelial keratoplasty (DSAEK). METHODS:
      This retrospective observational case series evaluated 47 consecutive corneal
      specimens from 42 patients who underwent either penetrating keratoplasty or
      repeated DSAEK for failed DSAEK. Clinical information was obtained for the cases.
      Sections of the specimens were examined using light microscopy.
      Immunohistochemical staining was performed for cytokeratins AE1/AE3 and for the
      myogenic marker smooth-muscle actin when indicated. Transmission electron
      microscopic examination was performed in some cases. RESULTS: Graft survival
      ranged from 0.5 to 34 months. Histologic examination showed that 94% of the
      specimens (44 of 47) had endothelial cell loss. Residual host Descemet membrane
      (19%; 9 of 47), fibrocellular tissue (19%; 9 of 47), epithelial implantation
      (15%; 7 of 47), and fungal infection (4%; 2 of 47) were also identified.
      Immunohistochemical stains were positive for AE1/AE3 in the epithelial
      implantations and for smooth-muscle actin in cells in the fibrocellular
      proliferations. CONCLUSIONS: The principal cause of failed DSAEK is endothelial
      cell loss. Residual host Descemet membrane, fibrocellular tissue at the edge of
      the lenticule, and epithelial implantation are common histologic findings. Fungal
      infection may occur in the setting of DSAEK.

PMID- 20696997
TI  - Punctate inner choroidopathy: clinical features and outcomes.
AB  - OBJECTIVE: To describe the clinical features and outcomes of a large group of
      patients with a spectrum of clinical appearances and diagnosed as having punctate
      inner choroidopathy (PIC). METHODS: In a retrospective consecutive case series,
      patients seen during a 16-year period at Moorfields Eye Hospital who were
      diagnosed as having PIC and had a minimum of 12 months' follow-up were included.
      Patients were classified as having typical PIC or atypical PIC (larger, presumed
      ocular histoplasmosis syndrome-like lesions). Main outcome measures included
      development of choroidal neovascularization, development of new PIC lesions, and
      final visual acuity. RESULTS: A total of 136 patients (271 eyes) were included.
      The average age was 32 years, 126 patients (93%) were female, and the mean
      refraction was -4.6 diopters. The overall mean follow-up was 6.2 years. Among 63
      normal fellow eyes, 56 (88%) remained unchanged, 3 (5%) developed PIC lesions,
      and 4 (6%) developed choroidal neovascularization. Eyes with PIC lesions remained
      unchanged in 49 of 74 cases (66%), with 9 (12%) developing new PIC lesions and 16
      (22%) developing choroidal neovascular membrane. In eyes with choroidal
      neovascularization, the mean logMAR visual acuity was 0.63 at study entry, 0.63
      at 12 months, 0.61 at 2 years, and 0.71 at final review (mean, 6.1 years).
      Overall, 40 eyes with PIC-related choroidal neovascular membrane (26%) had final
      visual acuity less than 6/60. No differences were observed between typical and
      atypical PIC eyes in any of the outcome measures or in any of the subgroup
      analyses. CONCLUSIONS: Punctate inner choroidopathy-related choroidal
      neovascularization was not visually benign. No differences were observed between
      eyes with typical and atypical choroidal lesions, supporting the notion that they
      represent a spectrum of a single disease, PIC.

PMID- 20696998
TI  - Central retinal findings in Bothnia dystrophy caused by RLBP1 sequence variation.
AB  - OBJECTIVE: To describe the central retinal findings early in the course of
      Bothnia dystrophy caused by the homozygous missense R234W sequence variation in
      the RLBP1 gene. METHODS: In 8 young patients with Bothnia dystrophy (aged 9-34
      years), high- and low-contrast distance visual acuity and visual fields were
      measured with Humphrey central (24-2) threshold testing and Goldmann perimetry.
      Central retinal thickness was measured with optical coherence tomography. Cross
      sectional images were analyzed and a linear scanning protocol was applied to
      examine retinitis punctata albescence in the posterior pole. RESULTS: Affected
      visual acuity (4 of 8 cases) and poor low-contrast visual acuity (8 of 8 cases)
      were found. Significant foveal depression and visual field loss were evident with
      Humphrey threshold testing at all ages, and paracentral and central scotomata in
      the second decade of life advanced in adulthood as verified with Goldmann
      perimetry. Optical coherence tomography showed generalized retinal thinning in
      the central foveal, foveal (innermost ring diameter [O], 1 mm), and inner ring
      (O, 3 mm) areas in all ages, and early retinal thinning was found in the inferior
      areas of the outer macula (O, 6 mm). Foveal and extrafoveal thinning of the
      retinal layers and outer nuclear layer were found. Homogeneous retinitis punctata
      albescence changes were visualized in and/or adjacent to the retinal pigment
      epithelium-choriocapillaris complex with high reflectance. CONCLUSIONS: In the
      RLBP1-Bothnia dystrophy phenotype, a loss of function and thinning of the central
      macula are found, indicating early damage of the cone photoreceptors in this
      disease of the visual cycle. Retinitis punctata albescence spots in the posterior
      pole are situated close to or in the retinal pigment epithelium-choriocapillaris
      complex.

PMID- 20696999
TI  - Mortality after diagnosis of small melanocytic lesions of the choroid.
AB  - OBJECTIVE: To evaluate the risk of dying of metastatic choroidal melanoma in
      patients with small, indeterminate, pigmented lesions of the uveal tract.
      METHODS: A cohort of 1063 consecutive patients were evaluated in the Ocular
      Oncology Clinic of the Massachusetts Eye and Ear Infirmary between January 1976
      and June 1996 with definite choroidal nevus (n = 256), indeterminate lesions (n =
      334), or small melanoma (n = 373). Deaths occurring up to December 1998 were
      identified through active follow-up or by a search of the National Death Index.
      Cumulative death rates were compared among diagnostic groups using the Kaplan
      Meier method. RESULTS: Mean lesion diameter was 4.6 mm in the nevi, 7.0 mm in the
      indeterminate lesions, and 8.1 mm in the small melanomas. Patients ranged in age
      from 3 to 95 years (median, 64 years). A total of 15 deaths due to ocular
      melanoma were ascertained (median follow-up of survivors, 8.2 years), 13 in the
      melanoma group and 2 in the indeterminate lesion group; actuarial tumor-specific
      death rates at 10 years after evaluation were 5% (95% confidence interval, 3%-8%)
      and 1% (95% confidence interval 0%-3%), respectively. No deaths due to ocular
      melanoma occurred in the nevus group. CONCLUSIONS: These data document the very
      low malignant potential of most indeterminate melanocytic lesions of the choroid
      and support the current practice of monitoring these tumors, with treatment
      provided when growth and other signs of malignant transformation are observed.

PMID- 20697000
TI  - Intraocular lymphatics in ciliary body melanomas with extraocular extension:
      functional for lymphatic spread?
AB  - OBJECTIVE: To assess the functional significance of intraocular tumor-associated
      lymphatic vessels in ciliary body melanomas with extraocular extension. METHODS:
      Twelve consecutive patients enucleated for a malignant melanoma of the ciliary
      body with extraocular extension and immunohistochemical presence of intraocular
      LYVE-1-positive and podoplanin-positive lymphatic vessels were examined for
      proliferation status and tumor invasion into tumor-associated lymphatics.
      Proliferating lymphatic vessels were identified using LYVE-1 and podoplanin as
      specific lymphatic endothelial markers and Ki-67 as the proliferation marker.
      Tumor invasion into lymphatic vessels was assessed using Melan-A as the melanoma
      marker. Kaplan-Meier analyses of survival and metastasis were performed. RESULTS:
      Intraocular proliferating lymphatic vessels were detected in all 12 ciliary body
      melanomas with extraocular extension. The ratio of proliferating lymphatics was
      significantly higher in the intraocular vs extraocular tumor compartment (P <
      .001). Extraocular lymphatic invasion by tumor cells was observed in 5 patients
      (42%), intraocular lymphatic invasion in 4 (33%), and synchronous intraocular and
      extraocular lymphatic invasion in 3 (25%). Detection of melanoma cells in
      intraocular and extraocular lymphatic vessels was significantly associated with
      higher risks of lymphatic spread (P < .001) and lower metastasis-free survival
      rates (P = .03). CONCLUSIONS: Intraocular tumor-associated lymphatic vessels
      contain proliferating endothelial cells and can be invaded by cancer cells in
      ciliary body melanomas with extraocular extension. Lymphatic invasion by tumor
      cells seems to be associated with an increased risk of lymphatic spread and
      mortality in these affected patients.

PMID- 20697001
TI  - Analysis of clinical misdiagnoses in children treated with enucleation.
AB  - OBJECTIVE: To evaluate discordant clinical and pathological diagnoses leading to
      pediatric enucleations over time. METHODS: All pathology reports of pediatric
      enucleation specimens (subjects aged 0 to 18 years) from 1960 to 2008 were
      reviewed. Specimens with discordant clinical and pathologic diagnoses were
      further analyzed. Formalin-fixed, paraffin-embedded sections of enucleated eyes
      of any misdiagnosed cases were reevaluated. RESULTS: Of 729 pediatric patients
      (746 eyes) who had enucleation from 1960 to 2008, 29 patients (4.0%) and 30 eyes
      (4.0%) had discordant clinical and pathological diagnoses. The misdiagnosis
      enucleation rate decreased with each respective decade studied, with the highest
      rate of 6.5% (18 of 276 eyes) in the 1960s and no misdiagnoses from 1990 to 2008.
      Of the 369 eyes enucleated for the clinical indication of malignancy, 22 eyes
      (6.0%) were misdiagnosed in that no evidence of malignancy was found on
      histopathological examination. Of the 377 eyes enucleated for benign clinical
      indications, 7 cases (1.9%) were found to be malignant by histopathology.
      CONCLUSIONS: Misdiagnoses leading to pediatric enucleation have decreased during
      the past 5 decades, likely owing to improved diagnostic techniques. Benign and
      malignant intraocular conditions can simulate each other, especially
      retinoblastoma, Coats disease, nematode and bacterial endophthalmitis,
      panuveitis, and persistent hyperplastic primary vitreous.

PMID- 20697002
TI  - Association of retinal vascular endothelial growth factor with avascular retina
      in a rat model of retinopathy of prematurity.
AB  - OBJECTIVE: To study the effects of oxygen fluctuations on rat vascular
      endothelial growth factor (VEGF), VEGF receptor 1(VEGFR1), and VEGFR2 in a model
      of retinopathy of prematurity (ROP). METHODS: Retinas at several postnatal days
      (p) were analyzed for VEGF splice variants, VEGFR1 and VEGFR2 messenger RNAs
      (mRNAs) using real-time polymerase chain reaction or for VEGF protein using
      enzyme-linked immunosorbent assay. RESULTS: Older developmental age was
      associated with VEGFR1 (P < .001), VEGF(120) (P < .001), and VEGF(188) (P = .03)
      mRNA overexpression. Expression of VEGFR2 and VEGF(164) mRNAs were associated
      with older age (P < .001) or exposure to the ROP model (P = .02 and P < .001,
      respectively). Expression of VEGF protein was greater at p14, when 30% avascular
      retina existed in the ROP model, compared with room air, when no avascular retina
      existed, and at p18, when intravitreous neovascularization existed in the model
      but not in room air (P < .001 for both). CONCLUSIONS: Unlike models of oxygen
      induced retinopathy that describe ROP before implementation of oxygen regulation,
      the ROP model re-creates oxygen stresses relevant to preterm infants with severe
      ROP today. Expression of VEGF(164) and VEGFR2 mRNAs and VEGF protein were
      increased in association with the ROP model and older developmental age and at
      time points when not only intravitreous neovascularization but also avascular
      retina were present in the ROP model and not in room air. Clinical Relevance
      Regulation of VEGF may have a role in the development of avascular retina and
      intravitreous neovascularization in some forms of severe ROP.

PMID- 20697003
TI  - Epidemiology of ulcerative keratitis in Northern California.
AB  - OBJECTIVE: To determine the incidence and associated risk factors for ulcerative
      keratitis in northern California. METHODS: In this large-population,
      retrospective, cohort study, all medical records with diagnosis coding for
      corneal ulcers during a consecutive 12-month period were reviewed. Incidence
      rates were calculated using a dynamic population model. Multivariate relative
      risk regression was conducted to evaluate potential risk factors for ulcerative
      keratitis. RESULTS: Within the target population of 1 093 210 patients, 302
      developed ulcerative keratitis. The incidence of ulcerative keratitis was 27.6
      per 100 000 person-years (95% confidence interval, 24.6-30.9). The incidence of
      corneal ulceration in contact lens wearers was 130.4 per 100 000 person-years
      (95% confidence interval, 111.3-151.7), with an adjusted relative risk of 9.31
      (7.42-11.7; P < .001) compared with non-contact lens wearers, who had an
      incidence of ulcerative keratitis of 14.0 per 100 000 person-years (11.7-16.6).
      Seven of 2944 people known to be infected with human immunodeficiency virus
      developed ulcerative keratitis, with 5 being contact lens wearers. The incidence
      of ulcerative keratitis in human immunodeficiency virus-positive patients was
      238.1 per 100 000 person-years (95% confidence interval, 95.7-490.5), with an
      odds ratio of 9.31 (7.42-11.7; P < .001) compared with human immunodeficiency
      virus-negative patients, who had an incidence of ulcerative keratitis of 27.1 per
      100 000 person-years (24.1-30.3). CONCLUSIONS: The incidence of ulcerative
      keratitis in this population is higher than previously reported. This may be
      owing to the increasing prevalence of contact lens wear.

PMID- 20697004
TI  - Smoking, socioeconomic factors, and age-related cataract: The Singapore Malay Eye
      study.
AB  - OBJECTIVE: To describe the relationship of smoking, sex, and socioeconomic
      factors with age-related cataract in Malay adults in Singapore. METHODS: In a
      population-based study, 3280 Malay individuals aged 40 to 80 years participated
      (78.7% response rate). All had interviews, systemic examination, and laboratory
      investigations. Lens opacity was graded from slitlamp and retroillumination
      photographs using the Wisconsin Cataract Grading System. Smoking-cataract
      associations were compared with the Blue Mountains Eye Study in Australia.
      RESULTS: Of 2927 participants (89.2%) with gradable lens photographs, 1338
      (45.7%) had cataract. After adjusting for age, sex, body mass index,
      hypertension, and diabetes, current smokers had a higher prevalence of nuclear
      cataract (odds ratio [OR], 2.06; 95% confidence interval [CI], 1.46-2.98),
      cortical cataract (OR, 1.33; 95% CI, 1.02-1.74), posterior subcapsular cataract
      (OR, 1.39; 95% CI, 1.02-1.91), or any cataract (OR, 1.48; 95% CI, 1.10-1.99).
      These associations were not seen in the Blue Mountains Eye Study. Primary or
      lower education (OR, 1.67; 95% CI, 1.06-2.64) and low monthly income (OR, 1.43;
      95% CI, 1.09-1.87) were both associated with nuclear cataract, while small-sized
      public housing was associated with posterior subcapsular cataract (OR, 1.70; 95%
      CI, 1.28-2.25). Among men, 43.5% currently smoked compared with only 3.2% of
      women. The population attributable risk of nuclear cataract due to smoking was
      estimated to be 17.6% in men. CONCLUSIONS: Smoking and indicators of low
      socioeconomic status were associated with cataract in Malay persons, with 1 in 6
      nuclear cataract cases in men attributable to smoking. Smoking-cataract
      associations were stronger in Malay than in white persons.

PMID- 20697005
TI  - An unusual retinal phenotype associated with a novel mutation in RHO.
AB  - OBJECTIVE: To report a new genetic variant in the rhodopsin gene (RHO) associated
      with an unusual autosomal dominant retinal phenotype. METHODS: Detailed
      phenotypic characterization was performed on affected family members spanning 4
      generations, including family history, best-corrected visual acuity, fundus
      examination, kinetic and static perimetry, full-field and multifocal
      electroretinography, fundus autofluorescence, and optical coherence tomography.
      For genetic testing, coding exons and flanking intronic regions of RHO were
      amplified with the use of polymerase chain reaction, purified, and sequenced.
      Cosegregation and control analysis were performed by direct sequencing of exon 3.
      Subsequent in silico analysis of the mutational consequence on protein function
      was undertaken. RESULTS: The onset of symptoms appeared in the fourth decade of
      life in this family, with moderate night blindness and asymmetrical visual loss.
      Affected members showed patchy areas of chorioretinal atrophy with decreased
      electroretinographic response amplitudes for both scotopic and photopic responses
      but no implicit time shift, consistent with restricted disease. A novel mutation
      in exon 3 of RHO was identified and represents a c.620T>A transition leading to a
      p.Met207Lys substitution. It cosegregated with this phenotype and was not
      identified in a control population. CONCLUSIONS: We report the phenotype-genotype
      correlation of an unusual autosomal dominant, late-onset restricted chorioretinal
      degeneration cosegregating with a novel RHO mutation, p.Met207Lys. A p.Met207Arg
      substitution has previously been reported to cause a distinct, generalized early
      onset rod-cone dystrophy. Clinical Relevance These data outline the phenotypic
      variability associated with RHO mutations. Depending on the localization and the
      amino acid substitution, patients may show congenital stationary night blindness,
      rod-cone dystrophy, sector retinitis pigmentosa, or localized chorioretinal
      atrophy.

PMID- 20697006
TI  - Ectopia lentis in a consanguineous pakistani family and a novel locus on
      chromosome 8q.
AB  - OBJECTIVE: To investigate the genetic basis and molecular characteristics of the
      isolated form of ectopia lentis. METHODS: We ascertained a consanguineous
      Pakistani family with multiple individuals with ectopia lentis. All affected as
      well as unaffected members with isolated ectopia lentis underwent detailed
      ophthalmologic and medical examination. Blood samples were collected and DNA was
      extracted. A genome-wide scan was completed with 382 polymorphic microsatellite
      markers, and logarithm of odds (LOD) scores were calculated. RESULTS: Maximum 2
      point LOD scores of 5.68 and 2.88 at theta = 0 were obtained for markers D8S285
      and D8S260, respectively, during the genome-wide scan. Additional microsatellite
      markers refined the disease locus to a 16.96-cM (14.07-Mb) interval flanked by
      D8S1737 proximally and D8S1117 distally. CONCLUSIONS: We report on a new locus
      for nonsyndromic autosomal recessive ectopia lentis on chromosome 8q11.23-q13.2
      in a consanguineous Pakistani family. Clinical Relevance Identification of
      genetic loci and genes involved in ectopia lentis will enhance our understanding
      of the disease at a molecular level, leading to better genetic counseling and
      family screening and possible future development of better treatment.

PMID- 20697007
TI  - Simultaneous vs sequential bilateral cataract surgery for infants with congenital
      cataracts: Visual outcomes, adverse events, and economic costs.
AB  - OBJECTIVES: To compare the incidence of adverse events and visual outcomes and to
      compare the economic costs of sequential vs simultaneous bilateral cataract
      surgery for infants with congenital cataracts. METHODS: Retrospective review of
      simultaneous vs sequential bilateral cataract surgery for infants with congenital
      cataracts who underwent cataract surgery when 6 months or younger at our
      institution. RESULTS: Records were available for 10 children who underwent
      sequential surgery at a mean age of 49 days for the first eye and 17 children who
      underwent simultaneous surgery at a mean age of 68 days (P = .25). We found a
      similar incidence of adverse events between the 2 treatment groups.
      Intraoperative or postoperative complications occurred in 14 eyes. The most
      common postoperative complication was glaucoma. No eyes developed
      endophthalmitis. The mean (SD) absolute interocular difference in logMAR visual
      acuities between the 2 treatment groups was 0.47 (0.76) for the sequential group
      and 0.44 (0.40) for the simultaneous group (P = .92). Payments for the hospital,
      drugs, supplies, and professional services were on average 21.9% lower per
      patient in the simultaneous group. CONCLUSIONS: Simultaneous bilateral cataract
      surgery for infants with congenital cataracts is associated with a 21.9%
      reduction in medical payments and no discernible difference in the incidence of
      adverse events or visual outcomes. However, our small sample size limits our
      ability to make meaningful comparisons of the relative risks and visual benefits
      of the 2 procedures.

PMID- 20697008
TI  - Socioeconomics of retinopathy of prematurity in-hospital care.
AB  - OBJECTIVE: To determine if there was any uniform experience across the United
      States relative to retinopathy of prematurity (ROP) services provided,
      reimbursement, and malpractice insurance coverage. METHODS: An online pediatric
      ophthalmology listserv poll queried pediatric ophthalmologists regarding ROP
      screening, reimbursement, malpractice insurance, and call and consult coverage.
      RESULTS: Compensation for providing ROP services is quite variable around the
      United States. The Southern respondents reported the highest contract income
      while the Northeast reported the lowest. The mean annual contract income was $63
      753 and the median annual contract income was $39 000. There was an even
      distribution between physicians vs hospitals providing malpractice coverage.
      There was also a fairly even distribution between physicians who do and do not
      provide consult and call coverage. CONCLUSIONS: Nationwide, there is no standard
      rate of compensation for ROP in-hospital care, coverage of liability insurance,
      or providing additional consult or on-call services. Income generation performing
      ROP screening examinations is roughly half what a pediatric ophthalmologist can
      generate by seeing patients in the clinic or performing surgery.

PMID- 20697010
TI  - Pars plana posterior capsulotomy in a patient with a telescope prosthesis for age
      related macular degeneration.
AB  - OBJECTIVE: To demonstrate a surgical technique for visualization and removal of
      visually significant posterior capsule opacification (PCO) in a patient with a
      telescope prosthesis for end-stage age-related macular degeneration, in what is
      to our knowledge the first reported case of visually significant PCO associated
      with the use of this device. METHODS: A pars plana capsulotomy using a 25-gauge
      vitrector was performed to remove PCO. RESULTS: Pars plana capsulotomy was
      performed and visual acuity improved to pre-PCO levels. Challenges associated
      with the management of this condition are discussed. CONCLUSIONS: The development
      of visually significant PCO in patients with a telescope prosthesis is a rare
      occurrence that poses a unique treatment dilemma. Given the risks of damaging the
      device with Nd:YAG laser, a method for pars plana capsulotomy using a 25-gauge
      vitrectomy instrument was determined and successfully performed to remove PCO in
      a telescope-implanted eye.

PMID- 20697009
TI  - Optic nerve regeneration.
AB  - Retinal ganglion cells are usually not able to regenerate their axons after optic
      nerve injury or degenerative disorders, resulting in lifelong visual loss. This
      situation can be partially reversed by activating the intrinsic growth state of
      retinal ganglion cells, maintaining their viability, and counteracting inhibitory
      signals in the extracellular environment. Advances during the past few years
      continue to extend the amount of regeneration that can be achieved in animal
      models. These findings give hope that clinically meaningful regeneration may
      become a reality within a few years if regenerating axons can be guided to their
      appropriate destinations.

PMID- 20697011
TI  - Surgery as the primary management of proliferative vitreoretinopathy: a history
      reflecting my experiences and biases.
AB  - Although attempts were made ot reattach retinas using proliferative
      vitreoretinopathy by various techniques before the 1970s, it was the development
      and subsequent refinement of closed-eye, mechanized pars plana vitrectomy that
      initiated the rapid rise in the surgical success rate. This article presents a
      personal history of the milestone accomplishments that facilitated the strong
      possibility of success that patients with proliferative vitreoretinopathy can now
      anticipate. Currently, various gasses, chemical compounds, and pharmaceutical
      agents serve adjunctively to advance surgical techniques with the expectation
      that they may be the primary curative procedure in the future. As in the past,
      what is unconventional today may be common tomorrow.

PMID- 20697012
TI  - Defining authorship for group studies.

PMID- 20697013
TI  - Simultaneous cataract surgery for bilateral congenital cataracts: are the cost
      savings worth the risk?

PMID- 20697014
TI  - Intravitreous ranibizumab as treatment for macular telangiectasia type 2.

PMID- 20697015
TI  - Exacerbation of zoster interstitial keratitis after zoster vaccination in an
      adult.

PMID- 20697016
TI  - Fluorescein angiography of recurrent retinopathy of prematurity after initial
      intravitreous bevacizumab treatment.

PMID- 20697017
TI  - Support for TGFB1 as a susceptibility gene for high myopia in individuals of
      Chinese descent.

PMID- 20697018
TI  - Orbital smooth muscle tumor associated with epstein-barr virus in a human
      immunodeficiency virus-positive patient.

PMID- 20697020
TI  - Diabetic retinopathy and sodium intake.

PMID- 20697021
TI  - Complex interactions between the sinoatrial node and atrium during reentrant
      arrhythmias in the canine heart.
AB  - BACKGROUND: Numerous studies implicate the sinoatrial node (SAN) as a participant
      in atrial arrhythmias, including atrial flutter (AFL) and atrial fibrillation
      (AF). However, the direct role of the SAN has never been described. METHODS AND
      RESULTS: The SAN was optically mapped in coronary perfused preparations from
      normal canine hearts (n=17). Optical action potentials were recorded during
      spontaneous rhythm, overdrive atrial pacing, and AF/AFL induced by acetylcholine
      (ACh; 0.3 to 3 micromol/L) and/or isoproterenol (Iso; 0.2 to 1 micromol/L). An
      optical action potential multiple component algorithm and dominant frequency
      analysis were used to reconstruct SAN activation and to identify specialized
      sinoatrial conduction pathways. Both ACh and Iso facilitated pacing-induced
      AF/AFL by shortening atrial repolarization. The entire SAN structure created a
      substrate for macroreentry with 9.6+/-1.7 Hz (69 episodes in all preparations).
      Atrial excitation waves could enter the SAN through the sinoatrial conduction
      pathways and overdrive suppress the node. The sinoatrial conduction pathways
      acted as a filter for atrial waves by slowing conduction and creating entrance
      block. ACh/Iso modulated filtering properties of the sinoatrial conduction
      pathways by increasing/decreasing the degree of the entrance block, respectively.
      Thus, the SAN could beat independently from AF/AFL reentrant activity during ACh
      (49+/-39%) and ACh/Iso (62+/-25%) (P=0.38). Without ACh, the AF/AFL waves
      captured the SAN and overdrive suppressed it. Spontaneous SAN activity could
      terminate or convert AFL to AF during cholinergic withdrawal. CONCLUSIONS: The
      specialized structure of the SAN can be a substrate for AF/AFL. Cholinergic
      stimulation not only can slow sinus rhythm and facilitate AF/AFL but also
      protects the intrinsic SAN function from the fast AF/AFL rhythm.

PMID- 20697022
TI  - Early atherosclerosis exhibits an enhanced procoagulant state.
AB  - BACKGROUND: Thrombin generation in vivo may be important in regulating
      atherosclerotic progression. In the present study, we examined for the first time
      the activity and presence of relevant coagulation proteins in relation to the
      progression of atherosclerosis. METHODS AND RESULTS: Both early and stable
      advanced atherosclerotic lesions were collected pairwise from each individual
      (n=27) during autopsy. Tissue homogenates were prepared from both total plaques
      and isolated plaque layers, in which the activity of factors (F) II, X, and XII
      and tissue factor was determined. Microarray analysis was implemented to
      elucidate local messenger RNA synthesis of coagulation proteins. Part of each
      specimen was paraffin embedded, and histological sections were
      immunohistochemically stained for multiple coagulation markers with the use of
      commercial antibodies. Data are expressed as median (interquartile range [IQR]).
      Tissue factor, FII, FX, and FXII activities were significantly higher in early
      atherosclerotic lesions than in stable advanced atherosclerotic lesions.
      Endogenous thrombin potential and thrombin-antithrombin complex values
      consolidated a procoagulant profile of early atherosclerotic lesions (endogenous
      thrombin potential, 1240 nmol/L x min [IQR, 1173 to 1311]; thrombin-antithrombin
      complex, 1045 ng/mg [IQR, 842.6 to 1376]) versus stable advanced atherosclerotic
      lesions (endogenous thrombin potential, 782 nmol/L x min [IQR, 0 to 1151];
      thrombin-antithrombin complex, 718.4 ng/mg [IQR, 508.6 to 1151]). Tissue factor,
      FVII, and FX colocalized with macrophages and smooth muscle cells. In addition,
      multiple procoagulant and anticoagulant proteases were immunohistochemically
      mapped to various locations throughout the atherosclerotic vessel wall in both
      early and advanced atherosclerotic stages. CONCLUSIONS: This study shows an
      enhanced procoagulant state of early-stage atherosclerotic plaques compared with
      advanced-stage plaques, which may provide novel insights into the role of
      coagulation during atherosclerotic plaque progression.

PMID- 20697023
TI  - Deficiency of antigen-presenting cell invariant chain reduces atherosclerosis in
      mice.
AB  - BACKGROUND: Adaptive immunity and innate immunity play important roles in
      atherogenesis. Invariant chain (CD74) mediates antigen-presenting cell antigen
      presentation and T-cell activation. This study tested the hypothesis that CD74
      deficient mice have reduced numbers of active T cells and resist atherogenesis.
      METHODS AND RESULTS: In low-density lipoprotein receptor-deficient (Ldlr(-/-))
      mice, CD74 deficiency (Ldlr(-/-)Cd74(-/-)) significantly reduced atherosclerosis
      and CD25(+)-activated T cells in the atheromata. Although Ldlr(-/-)Cd74(-/-) mice
      had decreased levels of plasma immunoglobulin (Ig) G1, IgG2b, and IgG2c against
      malondialdehyde-modified LDL (MDA-LDL), presumably as a result of impaired
      antigen-presenting cell function, Ldlr(-/-)Cd74(-/-) mice showed higher levels of
      anti-MDA-LDL IgM and IgG3. After immunization with MDA-LDL, Ldlr(-/-)Cd74(-/-)
      mice had lower levels of all anti-MDA-LDL Ig isotypes compared with Ldlr(-/-)
      mice. As anticipated, only Ldlr(-/-) splenocytes responded to in vitro
      stimulation with MDA-LDL, producing Th1/Th2 cytokines. Heat shock protein-65
      immunization enhanced atherogenesis in Ldlr(-/-) mice, but Ldlr(-/-) Cd74(-/-)
      mice remained protected. Compared with Ldlr(-/-) mice, Ldlr(-/-)Cd74(-/-) mice
      had higher anti-MDA-LDL autoantibody titers, fewer lesion CD25(+)-activated T
      cells, impaired release of Th1/Th2 cytokines from antigen-presenting cells after
      heat shock protein-65 stimulation, and reduced levels of all plasma anti-heat
      shock protein-65 Ig isotypes. Cytofluorimetry of splenocytes and peritoneal
      cavity cells of MDA-LDL- or heat shock protein-65-immunized mice showed increased
      percentages of autoantibody-producing marginal zone B and B-1 cells in Ldlr(-/
      )Cd74(-/-) mice compared with Ldlr(-/-) mice. CONCLUSIONS: Invariant chain
      deficiency in Ldlr(-/-) mice reduced atherosclerosis. This finding was associated
      with an impaired adaptive immune response to disease-specific antigens.
      Concomitantly, an unexpected increase in the number of innate-like peripheral B-1
      cell populations occurred, resulting in increased IgM/IgG3 titers to the
      oxidation-specific epitopes.

PMID- 20697024
TI  - A master of versatility to the heart's rescue: mast cells and ischemic
      preconditioning.

PMID- 20697025
TI  - Birth weight and atrial fibrillation: a causal link?

PMID- 20697026
TI  - Three-dimensional and molecular analysis of the venous pole of the developing
      human heart.
AB  - BACKGROUND: Various congenital malformations and many abnormal rhythms originate
      from the venous pole of the heart. Because of rapid changes during morphogenesis,
      lack of molecular and lineage data, and difficulties in presenting complex
      morphogenetic changes in the developing heart in a clear fashion, the development
      of this region in human has been difficult to grasp. METHODS AND RESULTS: To gain
      insight into the development of the different types of myocardium forming the
      venous pole of the human heart, we performed an immunohistochemical and 3
      dimensional analysis of serial sections of human embryos ranging from 22 through
      40 days of development. Three-dimensional models were prepared in a novel
      interactive portable format providing crucial spatial information and
      facilitating interpretation. As in the mouse, the systemic venous myocardium
      expresses the transcription factor TBX18, whereas the pulmonary venous myocardium
      expresses NKX2-5. In contrast to the mouse, a systemic venous sinus is identified
      upstream from the atrial chambers, albeit initially with nonmyocardial walls.
      From the outset, as in the mouse, the pulmonary vein empties to a chamber with
      atrial, rather than systemic venous, characteristics. Compared with the mouse,
      the vestibular spine is a more prominent structure. CONCLUSIONS: The similarities
      in gene expression in the distinctive types of myocardium surrounding the
      systemic and pulmonary venous tributaries in man and mouse permit extrapolation
      of the conclusions drawn from transgenic and lineage studies in the mouse to the
      human, showing that the systemic and pulmonary venous myocardial sleeves are
      derived from distinct developmental lineages.

PMID- 20697027
TI  - Aldehyde dehydrogenase activation prevents reperfusion arrhythmias by inhibiting
      local renin release from cardiac mast cells.
AB  - BACKGROUND: Renin released by ischemia/reperfusion from cardiac mast cells
      activates a local renin-angiotensin system (RAS). This exacerbates norepinephrine
      release and reperfusion arrhythmias (ventricular tachycardia and fibrillation),
      making RAS a new therapeutic target in myocardial ischemia. METHODS AND RESULTS:
      We investigated whether ischemic preconditioning (IPC) prevents cardiac RAS
      activation in guinea pig hearts ex vivo. When ischemia/reperfusion (20 minutes of
      ischemia/30 minutes of reperfusion) was preceded by IPC (two 5-minute
      ischemia/reperfusion cycles), renin and norepinephrine release and ventricular
      tachycardia and fibrillation duration were markedly decreased, a cardioprotective
      anti-RAS effect. Activation and blockade of adenosine A(2b)/A(3) receptors and
      activation and inhibition of protein kinase Cepsilon (PKCepsilon) mimicked and
      prevented, respectively, the anti-RAS effects of IPC. Moreover, activation of
      A(2b)/A(3) receptors or activation of PKCepsilon prevented degranulation and
      renin release elicited by peroxide in cultured mast cells (HMC-1). Activation and
      inhibition of mitochondrial aldehyde dehydrogenase type-2 (ALDH2) also mimicked
      and prevented, respectively, the cardioprotective anti-RAS effects of IPC.
      Furthermore, ALDH2 activation inhibited degranulation and renin release by
      reactive aldehydes in HMC-1. Notably, PKCepsilon and ALDH2 were both activated by
      A(2b)/A(3) receptor stimulation in HMC-1, and PKCepsilon inhibition prevented
      ALDH2 activation. CONCLUSIONS: The results uncover a signaling cascade initiated
      by A(2b)/A(3) receptors, which triggers PKCepsilon-mediated ALDH2 activation in
      cardiac mast cells, contributing to IPC-induced cardioprotection by preventing
      mast cell renin release and the dysfunctional consequences of local RAS
      activation. Thus, unlike classic IPC in which cardiac myocytes are the main
      target, cardiac mast cells are the critical site at which the cardioprotective
      anti-RAS effects of IPC develop.

PMID- 20697029
TI  - Exercise capacity and mortality in older men: a 20-year follow-up study.
AB  - BACKGROUND: Epidemiological findings, based largely on middle-aged populations,
      support an inverse and independent association between exercise capacity and
      mortality risk. The information available in older individuals is limited.
      METHODS AND RESULTS: Between 1986 and 2008, we assessed the association between
      exercise capacity and all-cause mortality in 5314 male veterans aged 65 to 92
      years (mean+/-SD, 71.4+/-5.0 years) who completed an exercise test at the
      Veterans Affairs Medical Centers in Washington, DC, and Palo Alto, Calif. We
      established fitness categories based on peak metabolic equivalents (METs)
      achieved. During a median 8.1 years of follow-up (range, 0.1 to 25.3), there were
      2137 deaths. Baseline exercise capacity was 6.3+/-2.4 METs among survivors and
      5.3+/-2.0 METs in those who died (P<0.001) and emerged as a strong predictor of
      mortality. For each 1-MET increase in exercise capacity, the adjusted hazard for
      death was 12% lower (hazard ratio=0.88; confidence interval, 0.86 to 0.90).
      Compared with the least fit individuals (< or =4 METs), the mortality risk was
      38% lower for those who achieved 5.1 to 6.0 METs (hazard ratio=0.62; confidence
      interval, 0.54 to 0.71) and progressively declined to 61% (hazard ratio=0.39;
      confidence interval, 0.32 to 0.49) for those who achieved >9 METs, regardless of
      age. Unfit individuals who improved their fitness status with serial testing had
      a 35% lower mortality risk (hazard ratio=0.65; confidence interval, 0.46 to 0.93)
      compared with those who remained unfit. CONCLUSIONS: Exercise capacity is an
      independent predictor of all-cause mortality in older men. The relationship is
      inverse and graded, with most survival benefits achieved in those with an
      exercise capacity >5 METs. Survival improved significantly when unfit individuals
      became fit.

PMID- 20697028
TI  - Birth weight is a significant risk factor for incident atrial fibrillation.
AB  - BACKGROUND: Few if any studies have assessed the relationship between birth
      weight and incident atrial fibrillation (AF). METHODS AND RESULTS: From 1993 to
      2009, we prospectively followed 27 982 women who were >45 years of age and free
      of cardiovascular disease and AF at baseline. Information on birth weight was
      categorized into 5 different categories: <2.5, 2.5 to 3.2, 3.2 to 3.9, 3.9 to
      4.5, and >4.5 kg. The primary outcome was time to incident AF. During 14.5 years
      of follow-up, 735 AF events occurred. Age-adjusted incidence rates for incident
      AF from the lowest to the highest birth weight category were 1.45, 1.82, 1.88,
      2.57, and 2.55 events per 1000 person-years of follow-up. After multivariable
      adjustment, hazard ratios for incident AF across increasing birth weight
      categories were 1.0, 1.30 (95% confidence interval [CI], 0.96 to 1.75), 1.28 (95%
      CI, 0.96 to 1.69), 1.70 (95% CI, 1.23 to 2.37), and 1.71 (95% CI, 1.12 to 2.61)
      (P for linear trend=0.002). Adding body mass index, blood pressure, and diabetes
      mellitus at study entry did not have a large effect on these estimates (P for
      linear trend=0.004). In contrast, including height in the multivariable model
      substantially attenuated the relationship between birth weight and AF (P for
      linear trend=0.17), and additional adjustment for maximum weight in young
      adulthood further attenuated this association (multivariable-adjusted hazard
      ratio across birth weight categories, 1.0, 1.27 [95% CI, 0.94 to 1.71], 1.10 [95%
      CI, 0.83 to 1.46], 1.41 [95% CI, 1.01 to 1.96], and 1.29 [95% CI, 0.84 to 1.98];
      P for linear trend=0.23). CONCLUSIONS: Birth weight is significantly associated
      with incident AF among women, suggesting that early life determinants may play an
      important role in the pathogenesis of AF. CLINICAL TRIAL REGISTRATION: URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT00000479.

PMID- 20697031
TI  - Plasma beta-amyloid and cognitive decline.
AB  - OBJECTIVES: To determine if plasma beta-amyloid (Abeta) levels (1) can be linked
      to specific cognitive changes that constitute conversion to Alzheimer disease
      (AD) and (2) correspond to cognitive change independent of dementia. DESIGN:
      Longitudinal study including 3 visits during approximately 41/2 years (2000
      2006). SETTING: Northern Manhattan community. PARTICIPANTS: Eight hundred eighty
      individuals from a population-based and ethnically diverse sample who had 2
      plasma Abeta measurements and were dementia free at the time of the first Abeta
      sample; 481 remained cognitively healthy, 329 were cognitively or functionally
      impaired but not demented at any point, and 70 developed AD. MAIN OUTCOME
      MEASURES: General estimating equations tested the association between plasma
      Abeta (baseline and change in values) and cognitive change (composite score and
      memory, language, and visuospatial indices). RESULTS: High baseline plasma
      Abeta42 (P = .01) and Abeta40 (P = .01) and decreasing/relatively stable Abeta42
      (P = .01) values were associated with faster decline in multiple cognitive
      domains. In those who remained cognitively healthy, high baseline plasma Abeta42
      (P = .01) and decreasing/relatively stable plasma Abeta42 (P = .01) was
      associated with faster cognitive decline, primarily in memory. CONCLUSIONS: The
      association between plasma Abeta and multiple aspects of cognition more clearly
      specifies the previously documented downward trajectory of plasma Abeta with AD
      onset. The predominant association with memory seen only in healthy elderly
      individuals also suggests that plasma Abeta is linked with even earlier
      neurologic changes that may or may not culminate in dementia.

PMID- 20697032
TI  - Persistence with stroke prevention medications 3 months after hospitalization.
AB  - OBJECTIVE: To measure longitudinal use of stroke prevention medications following
      stroke hospital discharge. We hypothesized that a combination of patient-,
      provider-, and system-level factors influence medication-taking behavior. DESIGN:
      Observational cohort design. SETTING: One hundred six US hospitals participating
      in the American Heart Association Get With The Guidelines-Stroke program.
      PATIENTS: Two thousand eight hundred eighty-eight patients 18 years or older
      admitted with ischemic stroke or transient ischemic attack. MAIN OUTCOME MEASURE:
      Regimen persistence, including use of antiplatelet therapies, warfarin,
      antihypertensive therapies, lipid-lowering therapies, or diabetes medications,
      from discharge to 3 months. Reasons for nonpersistence were also ascertained.
      RESULTS: Two thousand five hundred ninety-eight patients (90.0%) were eligible
      for analysis. At 3 months, 75.5% of subjects continued taking all secondary
      prevention medications prescribed at discharge. Persistence at 3 months was
      associated with decreasing number of medication classes prescribed, increasing
      age, medical history, less severe stroke disability, having insurance, working
      status, understanding why medications are prescribed and how to refill them,
      increased quality of life, financial hardship, geographic region, and hospital
      size. CONCLUSIONS: One-quarter of stroke patients reported discontinuing 1 or
      more of their prescribed regimen of secondary prevention medications within 3
      months of hospitalization for an acute stroke. Several modifiable factors
      associated with regimen persistence were identified and could be targets for
      improving long-term secondary stroke prevention.

PMID- 20697033
TI  - Chaperone-mediated autophagy markers in Parkinson disease brains.
AB  - OBJECTIVE: To investigate chaperone-mediated autophagy in the pathogenesis of
      Parkinson disease (PD). DESIGN: Postmortem observational study. SETTING:
      University Department of Clinical Neuroscience, Institute of Neurology,
      University College London. SUBJECTS: Postmortem samples from 7 PD, 6 Alzheimer
      disease (AD), and 8 control brains. MAIN OUTCOME MEASURE: Lysosomal-associated
      membrane protein 2A (LAMP2A) and heat shock cognate 70 (hsc70) protein levels
      were compared in the substantia nigra pars compacta and amygdala of PD, AD, and
      control brain samples. To provide insight into the turnover of alpha-synuclein,
      degradation pathways for this protein were studied in a dopaminergic cell line.
      RESULTS: The expression levels of the chaperone-mediated autophagy proteins
      LAMP2A and hsc70 were significantly reduced in the substantia nigra pars compacta
      and amygdala of PD brains compared with age-matched AD and control brain samples.
      Lewy bodies in these regions contained autophagy-related proteins. We
      demonstrated that decreased LAMP2A levels in dopaminergic cell lines reduced
      chaperone-mediated autophagy activity and increased the half-life of alpha
      synuclein. CONCLUSIONS: These findings suggest that there is reduced chaperone
      mediated autophagy activity in the PD brain, provide evidence for the role of
      autophagy in PD pathogenesis and Lewy body formation, and suggest that this
      pathway may be a suitable therapeutic target in PD.

PMID- 20697034
TI  - Prospects for minocycline neuroprotection.
AB  - Minocycline is a clinically available antibiotic and anti-inflammatory drug that
      also demonstrates neuroprotective properties in a variety of experimental models
      of neurological diseases. There have thus far been more than 300 publications on
      minocycline neuroprotection, including a growing number of human studies. Our
      objective is to critically review the biological basis and translational
      potential of this action of minocycline on the nervous system.

PMID- 20697035
TI  - Brugada-type electrocardiographic changes induced by long-term lithium use.

PMID- 20697030
TI  - Meta-analysis confirms CR1, CLU, and PICALM as alzheimer disease risk loci and
      reveals interactions with APOE genotypes.
AB  - OBJECTIVES: To determine whether genotypes at CLU, PICALM, and CR1 confer risk
      for Alzheimer disease (AD) and whether risk for AD associated with these genes is
      influenced by apolipoprotein E (APOE) genotypes. DESIGN: Association study of AD
      and CLU, PICALM, CR1, and APOE genotypes. SETTING: Academic research institutions
      in the United States, Canada, and Israel. PARTICIPANTS: Seven thousand seventy
      cases with AD, 3055 with autopsies, and 8169 elderly cognitively normal controls,
      1092 with autopsies, from 12 different studies, including white, African
      American, Israeli-Arab, and Caribbean Hispanic individuals. RESULTS: Unadjusted,
      CLU (odds ratio [OR], 0.91; 95% confidence interval [CI], 0.85-0.96 for single
      nucleotide polymorphism [SNP] rs11136000), CR1 (OR, 1.14; 95% CI, 1.07-1.22; SNP
      rs3818361), and PICALM (OR, 0.89; 95% CI, 0.84-0.94, SNP rs3851179) were
      associated with AD in white individuals. None were significantly associated with
      AD in the other ethnic groups. APOE epsilon4 was significantly associated with AD
      (ORs, 1.80-9.05) in all but 1 small white cohort and in the Arab cohort.
      Adjusting for age, sex, and the presence of at least 1 APOE epsilon4 allele
      greatly reduced evidence for association with PICALM but not CR1 or CLU. Models
      with the main SNP effect, presence or absence of APOE epsilon4, and an
      interaction term showed significant interaction between presence or absence of
      APOE epsilon4 and PICALM. CONCLUSIONS: We confirm in a completely independent
      data set that CR1, CLU, and PICALM are AD susceptibility loci in European
      ancestry populations. Genotypes at PICALM confer risk predominantly in APOE
      epsilon4-positive subjects. Thus, APOE and PICALM synergistically interact.

PMID- 20697036
TI  - Letter by Quintao regarding article, "Association of circulating cholesteryl
      ester transfer protein activity with incidence of cardiovascular disease in the
      community".

PMID- 20697037
TI  - Letter by Opolski et al regarding article, "Patient characteristics and cell
      source determine the number of isolated human cardiac progenitor cells".

PMID- 20697039
TI  - Cholesterol embolization syndrome.

PMID- 20697040
TI  - Percutaneous deep vein stenting to prevent recurrent pulmonary thromboembolism
      from axillary venous malformation.

PMID- 20697041
TI  - Sharpen that needle.

PMID- 20697043
TI  - Frequency and prognosis of convulsive status epilepticus of different causes: a
      systematic review.
AB  - We conducted a systematic review of all studies of status epilepticus (SE) with
      more than 30 patients published between January 1, 1990, and December 31, 2008,
      to determine the frequencies of the common underlying causes and the extent to
      which the underlying causes affect the prognosis of an episode of SE. The
      frequencies of underlying causes vary among studies and show marked geographic
      differences, but in most studies, the most common underlying causes were
      cerebrovascular disease and low antiepileptic drug levels. A relatively good
      prognosis of SE is found when the underlying cause is associated with low
      antiepileptic drug levels or alcohol abuse, and a relatively poor outcome occurs
      when the underlying cause is cerebrovascular disease, particularly in the case of
      SE due to acute cerebral anoxia, but in most conditions, the reported prognosis
      is variable. Also, when SE occurs in the context of an acute cerebral insult,
      such as cerebral infection or cerebrovascular disease, the prognosis of the acute
      cerebral event is worsened.

PMID- 20697042
TI  - Natalizumab and progressive multifocal leukoencephalopathy: what are the causal
      factors and can it be avoided?
AB  - Natalizumab (Tysabri) was the first monoclonal antibody approved for the
      treatment of relapsing forms of multiple sclerosis (MS). After its initial
      approval, 3 patients undergoing natalizumab therapy in combination with other
      immunoregulatory and immunosuppressive agents were diagnosed with progressive
      multifocal leukoencephalopathy (PML). The agent was later reapproved and its use
      restricted to monotherapy in patients with relapsing forms of MS. Since
      reapproval in 2006, additional cases of PML were reported in patients with MS
      receiving natalizumab monotherapy. Thus, there is currently no convincing
      evidence that natalizumab-associated PML is restricted to combination therapy
      with other disease-modifying or immunosuppressive agents. In addition, recent
      data indicate that risk of PML might increase beyond 24 months of treatment.

PMID- 20697044
TI  - A phase 3, double-blind, placebo-controlled trial of idebenone in friedreich
      ataxia.
AB  - OBJECTIVE: To assess the efficacy of idebenone on neurological function in
      patients with Friedreich ataxia. DESIGN: Randomized, double-blind, placebo
      controlled intervention trial. SETTING: Children's Hospital of Philadelphia and
      the University of California at Los Angeles. PARTICIPANTS: Seventy ambulatory
      pediatric patients (age, 8-18 years) with a baseline International Cooperative
      Ataxia Rating Scale (ICARS) score of 10 to 54. INTERVENTIONS: Participants were
      randomized into 1 of 3 treatment arms: 450 or 900 mg of idebenone per day (in
      those with a body weight < or = or >45 kg, respectively; n = 22); 1350 or 2250 mg
      of idebenone per day (n = 24); or placebo (n = 24). MAIN OUTCOME MEASURES: Mean
      change from baseline to week 24 in ICARS score was the primary efficacy variable.
      Mean change in Friedreich Ataxia Rating Scale (FARS) score, performance measures,
      and activities of daily living were the secondary efficacy variables. RESULTS:
      Patients who received idebenone improved by 2.5 points on mean ICARS score
      compared with baseline, while patients in the placebo group improved by 1.3
      points. Patients who took idebenone also improved by 1.6 points on the FARS,
      while patients taking placebo declined by 0.6 points. For both end points, the
      difference between the idebenone and placebo groups was not statistically
      different. CONCLUSIONS: Idebenone did not significantly alter neurological
      function in Friedreich ataxia during the 6-month study. Larger studies of longer
      duration may be needed to assess the therapeutic potential of drug candidates on
      neurological function in Friedreich ataxia. Trial Registration clinicaltrials.gov
      Identifier: NCT00537680.

PMID- 20697046
TI  - Management of thrombolysis-associated symptomatic intracerebral hemorrhage.
AB  - BACKGROUND: Symptomatic intracerebral hemorrhage (sICH) is the most devastating
      complication of thrombolytic therapy for acute stroke. It is not clear whether
      patients with sICH continue to bleed after diagnosis, nor has the most
      appropriate treatment been determined. METHODS: We performed a retrospective
      analysis of our prospectively collected Get With the Guidelines-Stroke database
      between April 1, 2003, and December 31, 2007. Radiologic images and all
      procoagulant agents used were reviewed. Multivariable logistic regression was
      performed to identify factors associated with in-hospital mortality. RESULTS: Of
      2362 patients with acute ischemic stroke during the study period, sICH occurred
      in 19 of the 311 patients (6.1%) who received intravenous tissue plasminogen
      activator and 2 of the 72 (2.8%) who received intra-arterial thrombolysis. In
      hospital mortality was significantly higher in patients with sICH than in those
      without (15 of 20 [75.0]% vs 56 of 332 [16.9%], P < .001). Eleven of 20 patients
      (55.0%) received therapy for coagulopathy: 7 received fresh frozen plasma; 5,
      cryoprecipitate; 4, phytonadione (vitamin K(1)); 3, platelets; and 1,
      aminocaproic acid. Independent predictors of in-hospital mortality included sICH
      (odds ratio, 32.6; 95% confidence interval, 8.8-120.2), increasing National
      Institutes of Health Stroke Scale score (1.2; 1.1-1.2), older age (1.3; 1.0-1.7),
      and intra-arterial thrombolysis (2.9; 1.4-6.0). Treatment for coagulopathy was
      not associated with outcome. Continued bleeding (>33% increase in intracerebral
      hemorrhage volume) occurred in 4 of 10 patients with follow-up scans available
      (40.0%). CONCLUSIONS: In many patients with sICH after thrombolysis, coagulopathy
      goes untreated. Our finding of continued bleeding after diagnosis in 40.0% of
      patients suggests a powerful opportunity for intervention. A multicenter registry
      to analyze management of thrombolysis-associated intracerebral hemorrhage and
      outcomes is warranted.

PMID- 20697045
TI  - Diagnosis-independent Alzheimer disease biomarker signature in cognitively normal
      elderly people.
AB  - OBJECTIVE: To identify biomarker patterns typical for Alzheimer disease (AD) in
      an independent, unsupervised way, without using information on the clinical
      diagnosis. DESIGN: Mixture modeling approach. SETTING: Alzheimer's Disease
      Neuroimaging Initiative database. PATIENTS OR OTHER PARTICIPANTS: Cognitively
      normal persons, patients with AD, and individuals with mild cognitive impairment.
      MAIN OUTCOME MEASURES: Cerebrospinal fluid-derived beta-amyloid protein 1-42,
      total tau protein, and phosphorylated tau(181P) protein concentrations were used
      as biomarkers on a clinically well-characterized data set. The outcome of the
      qualification analysis was validated on 2 additional data sets, 1 of which was
      autopsy confirmed. RESULTS: Using the US Alzheimer's Disease Neuroimaging
      Initiative data set, a cerebrospinal fluid beta-amyloid protein 1
      42/phosphorylated tau(181P) biomarker mixture model identified 1 feature linked
      to AD, while the other matched the "healthy" status. The AD signature was found
      in 90%, 72%, and 36% of patients in the AD, mild cognitive impairment, and
      cognitively normal groups, respectively. The cognitively normal group with the AD
      signature was enriched in apolipoprotein E epsilon4 allele carriers. Results were
      validated on 2 other data sets. In 1 study consisting of 68 autopsy-confirmed AD
      cases, 64 of 68 patients (94% sensitivity) were correctly classified with the AD
      feature. In another data set with patients (n = 57) with mild cognitive
      impairment followed up for 5 years, the model showed a sensitivity of 100% in
      patients progressing to AD. CONCLUSIONS: The mixture modeling approach, totally
      independent of clinical AD diagnosis, correctly classified patients with AD. The
      unexpected presence of the AD signature in more than one-third of cognitively
      normal subjects suggests that AD pathology is active and detectable earlier than
      has heretofore been envisioned.

PMID- 20697047
TI  - Association of alpha-, beta-, and gamma-Synuclein with diffuse lewy body disease.
AB  - OBJECTIVE: To determine the association of the genes that encode alpha-, beta-,
      and gamma-synuclein (SNCA, SNCB, and SNCG, respectively) with diffuse Lewy body
      disease (DLBD). DESIGN: Case-control study. Subjects A total of 172 patients with
      DLBD consistent with a clinical diagnosis of Parkinson disease dementia/dementia
      with Lewy bodies and 350 clinically and 97 pathologically normal controls.
      INTERVENTIONS: Sequencing of SNCA, SNCB, and SNCG and genotyping of single
      nucleotide polymorphisms performed on an Applied Biosystems capillary sequencer
      and a Sequenom MassArray pLEX platform, respectively. Associations were
      determined using chi(2) or Fisher exact tests. RESULTS: Initial sequencing
      studies of the coding regions of each gene in 89 patients with DLBD did not
      detect any pathogenic substitutions. Nevertheless, genotyping of known
      polymorphic variability in sequence-conserved regions detected several single
      nucleotide polymorphisms in the SNCA and SNCG genes that were significantly
      associated with disease (P = .05 to <.001). Significant association was also
      observed for 3 single-nucleotide polymorphisms located in SNCB when comparing
      DLBD cases and pathologically confirmed normal controls (P = .03-.01); however,
      this association was not significant for the clinical controls alone or the
      combined clinical and pathological controls (P > .05). After correction for
      multiple testing, only 1 single-nucleotide polymorphism in SNCG (rs3750823)
      remained significant in all of the analyses (P = .05-.009). CONCLUSION: These
      findings suggest that variants in all 3 members of the synuclein gene family,
      particularly SNCA and SNCG, affect the risk of developing DLBD and warrant
      further investigation in larger, pathologically defined data sets as well as
      clinically diagnosed Parkinson disease/dementia with Lewy bodies case-control
      series.

PMID- 20697048
TI  - Autonomic symptoms in carriers of the m.3243A>G mitochondrial DNA mutation.
AB  - BACKGROUND: The m.3243A>G mutation can cause multisystem medical problems and can
      affect the autonomic nervous system. OBJECTIVE: To study the frequency and
      spectrum of autonomic symptoms associated with the m.3243A>G mitochondrial DNA
      point mutation. Design, Setting, and Patients We studied a cohort of 88
      matrilineal relatives from 40 families, including 35 fully symptomatic patients
      with mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike
      episodes (MELAS), 53 carrier relatives, and 16 controls using a questionnaire
      based on existing standard instruments for the evaluation of autonomic
      dysfunction. We compared the questionnaire with an expert evaluation. We compared
      data among the 3 groups using the Mantel-Haenszel chi(2) test to determine the
      statistical significance of differences between groups. RESULTS: Mutation
      carriers frequently had symptoms of autonomic dysfunction, specifically
      gastrointestinal and orthostatic intolerance. CONCLUSIONS: Carriers of the
      m.3243A>G mutation have frequent autonomic symptoms. The m.3243A>G mutation
      should be considered as an etiological factor in patients with autonomic
      dysfunction and a medical or family history suggestive of mitochondrial disease.
      Because some autonomic symptoms are treatable, early detection and proactive
      management may mitigate the burden of morbidity.

PMID- 20697049
TI  - The trajectory of gait speed preceding mild cognitive impairment.
AB  - OBJECTIVES: To compare the trajectory of motor decline, as measured by gait speed
      and finger-tapping speed, between elderly people who developed mild cognitive
      impairment (MCI) and those who remained cognitively intact. We also sought to
      determine the approximate time at which the decline in motor function accelerated
      in persons who developed MCI. DESIGN: Longitudinal cohort study. PARTICIPANTS:
      Participants were 204 healthy seniors (57.8% women) from the Oregon Brain Aging
      Study evaluated for up to 20 years using annual neurologic, neuropsychological,
      and motor examinations. MAIN OUTCOME MEASURES: The pattern of motor decline with
      aging was compared using a mixed-effects model with an interaction term for age
      and a clinical diagnosis of MCI. The time before diagnosis of MCI, when the
      change in gait or finger-tapping speed accelerates, was assessed using a mixed
      effects model with a change point for men and women, separately and combined, who
      developed MCI. RESULTS: The rates of change, with aging, in gait speed (P < .001)
      and finger-tapping speed in the dominant hand (P = .003) and nondominant hand (P
      < .001) were significantly different between participants who developed MCI
      (converters) and those who did not (nonconverters). Using a change point analysis
      for MCI converters, the decrease in gait speed accelerated by 0.023 m/s/y (P <
      .001), occurring 12.1 years before the onset of MCI. An acceleration in gait
      speed decline occurred earlier in men than women. For tapping speed, the change
      point occurred after the onset of MCI for both dominant and nondominant hands
      when men and women were combined. CONCLUSIONS: Motor decline as indexed by gait
      speed accelerates up to 12 years before MCI. Longitudinal changes in motor
      function may be useful in the early detection of dementia during preclinical
      stages, when the utility of disease-modifying therapies would be greatest.

PMID- 20697050
TI  - Hereditary cerebral hemorrhage with amyloidosis associated with the E693K
      mutation of APP.
AB  - OBJECTIVE: To report the clinical, genetic, neuroimaging, and neuropathologic
      studies of patients with the hereditary cerebral hemorrhage with amyloidosis
      linked to the APP E693K mutation. DESIGN: Case series. Clinical details and
      laboratory results were collected by direct evaluation and previous medical
      records. DNA analysis was carried out in several affected subjects and healthy
      individuals. Neuropathologic examination was performed in 2 subjects. SETTING:
      Southern Lombardy, Italy. Patients Individuals with and without amyloidosis in 4
      unrelated Italian families (N = 37). Main Outcome Measure Genotype-phenotype
      relationship. RESULTS: The affected individuals presented with recurrent headache
      and multiple strokes, followed by epilepsy and cognitive decline in most of them.
      The disease was inherited with an autosomal dominant trait and segregated with
      the APP E693K mutation. Neuroimaging demonstrated small to large hematomas,
      subarachnoid bleeding, scars with hemosiderin deposits, small infarcts, and
      leukoaraiosis. Amyloid-beta immunoreactivity was detected in the wall of
      leptomeningeal and parenchymal vessels and in the neuropil, whereas
      phosphorylated tau, neurofibrillary changes, and neuritic plaques were absent.
      CONCLUSIONS: These findings expand the number of APP mutations linked to
      hereditary cerebral hemorrhage with amyloidosis, reinforcing the link between
      this phenotype and codon 693 of APP.

PMID- 20697051
TI  - A 12-year population-based study of psychosis in Parkinson disease.
AB  - OBJECTIVE: To investigate the prevalence, incidence, risk factors, and
      concomitants of Parkinson disease (PD)-associated psychosis (PDP) in a population
      based prevalent cohort. DESIGN: Prospective longitudinal cohort study. SETTING:
      Community-based study in southwestern Norway. PARTICIPANTS: Two hundred thirty
      community-based PD patients were followed up prospectively for 12 years.
      Reassessments were conducted at 4 and 8 years and then annually. MAIN OUTCOME
      MEASURES: Severity of PDP was measured by the Unified Parkinson Disease Rating
      Scale thought disorder (UPDRS-TD) item. Patients with a UPDRS-TD score of 2 or
      more or those taking antipsychotic drugs owing to psychotic symptoms were
      categorized at each visit as having PDP. Generalized estimating equations were
      applied to investigate baseline risk factors for incident PDP and clinical and
      demographic concomitants of PDP during 12 years. RESULTS: By study's end, 137
      patients (60%) had developed hallucinations or delusions. The incidence rate of
      PDP was 79.7 per 1000 person-years. Higher age at onset, higher baseline levodopa
      equivalent doses, probable rapid eye movement (REM) sleep behavior disorder at
      baseline, and follow-up time were independent risk factors of incident PDP.
      Significant concomitant features of patients with PDP during the 12-year study
      period were low activities of daily living function (UPDRS II), dementia, high
      levodopa-equivalent dose, and probable REM sleep behavior disorder. CONCLUSIONS:
      Psychotic symptoms affect most patients with PD, with increased risk in those
      with higher age at onset, need for high doses of dopaminergic drugs, and probable
      REM sleep behavior disorder. This risk factor pattern and the observed
      associations with increased disability and dementia place PDP within a symptom
      complex signaling a malignant disease course.

PMID- 20697052
TI  - Amyotrophic lateral sclerosis-frontotemporal lobar dementia in 3 families with
      p.Ala382Thr TARDBP mutations.
AB  - BACKGROUND: TAR DNA-binding protein 43, encoded by the TARDBP gene, has been
      identified as the major pathological protein of frontotemporal lobar dementia
      (FTLD) with or without amyotrophic lateral sclerosis (ALS) and sporadic ALS.
      Subsequently, mutations in the TARDBP gene have been detected in 2% to 3% of
      patients with ALS (both familial and sporadic ALS). However, to our knowledge,
      there is only 1 description of 2 patients with FTLD and TARDBP gene mutations who
      later developed motor neuron disease. OBJECTIVE: To describe cognitive
      abnormalities in 3 Italian families with familial ALS and TARDBP gene mutations.
      DESIGN, SETTING, AND PARTICIPANTS: Genetic, neuropsychological, and neuroimaging
      analyses in 36 patients with familial non-superoxide dismutase 1 gene (SOD1) ALS
      and 280 healthy controls. Main Outcome Measure We identified 3 index cases of
      familial ALS carrying the p.Ala382Thr missense mutation of the TARDBP gene and
      with clinical, neuroimaging, and neuropsychological features of FTLD. RESULTS:
      The p.Ala382Thr missense mutation of the TARDBP gene was absent in the 280
      controls. It was present in all affected members of the 3 families for whom DNA
      was available. All affected members of the 3 families developed FTLD after the
      onset of ALS, confirmed by neuropsychological testing and hypometabolism in
      frontal associative areas assessed with fludeoxyglucose F 18 positron emission
      tomography and computed tomography. CONCLUSIONS: Three apparently unrelated
      families with familial ALS carrying the p.Ala382Thr TARDBP missense mutation
      developed FTLD. In these families, FTLD cosegregates with ALS. Patients with ALS
      carrying TARDBP mutations may develop FTLD.

PMID- 20697053
TI  - A purpose-oriented life: is it potentially neuroprotective?

PMID- 20697054
TI  - Bilateral pallidal stimulation for x-linked dystonia parkinsonism.
AB  - OBJECTIVE: To report the clinical benefits of bilateral deep brain stimulation
      (DBS) of the globus pallidus internus (GPi) in a patient with X-linked dystonia
      parkinsonism (XDP). DESIGN: Case report. SETTING: Tertiary referral center.
      Patient A 40-year-old Filipino man with genetically confirmed XDP and severely
      disabling generalized dystonia. Intervention Bilateral GPi DBS. MAIN OUTCOME
      MEASURES: The primary outcome measures were the Burke-Fahn-Marsden Dystonia Scale
      (BFMDS) severity and disability scores, and the secondary outcome measure was the
      Unified Parkinson Disease Rating Scores. RESULTS: At the 1-year postoperative
      follow-up, there was 80.4% improvement in the BFMDS severity score and 66.7%
      improvement in the BFMDS disability score. CONCLUSION: Bilateral GPi DBS seems to
      be very effective in improving dystonia in XDP.

PMID- 20697055
TI  - Interferon Beta treatment in neuromyelitis optica: increase in relapses and
      aquaporin 4 antibody titers.
AB  - OBJECTIVE: To describe a patient with neuromyelitis optica (NMO) whose aquaporin
      4 (AQP4) antibody levels increased following treatment with interferon beta.
      DESIGN: Prospective clinical and laboratory case report. SETTING: Institutional
      referral center for multiple sclerosis (MS). Patient One patient with an initial
      diagnosis of MS that was later revised to NMO. INTERVENTIONS: A course of
      interferon beta-1a followed by conventional immunosuppression. Blood samples were
      collected from the onset of treatment, and clinical and laboratory assessment was
      performed. MAIN OUTCOME MEASURES: Serum levels of AQP4 antibody and number and
      characteristics of neurological relapses. RESULTS: After 3 relapses during a 10
      month period despite interferon beta-1a treatment, the diagnosis of AQP4 antibody
      positive NMO was made and treatment was switched to prednisolone and
      methotrexate. The AQP4 antibody titers rose dramatically during treatment with
      interferon beta, and then fell when conventional immunosuppressive therapy was
      substituted; the patient has remained relapse-free for the subsequent years.
      CONCLUSIONS: Although previous articles have suggested that interferon beta may
      increase relapses in NMO, this is the first to illustrate an increase in AQP4
      antibodies associated with such treatment.

PMID- 20697056
TI  - Longitudinally extensive transverse myelitis following vaccination with nasal
      attenuated novel influenza A(H1N1) vaccine.
AB  - BACKGROUND: Transverse myelitis has been reported in association with
      vaccination, including influenza vaccination. OBJECTIVE: To describe a case of
      longitudinally extensive transverse myelitis associated with vaccination with a
      nasal attenuated novel influenza A(H1N1) vaccine. DESIGN: Case report. SETTING:
      Sanford University of South Dakota Hospital. Patient A 27-year-old woman with
      longitudinally extensive transverse myelitis. RESULTS: Four days following novel
      influenza A(H1N1) vaccination, the patient developed longitudinally extensive
      transverse myelitis. Extensive diagnostic evaluation effectively ruled out causes
      other than vaccination-associated transverse myelitis. Following treatment with
      corticosteroids and plasmapheresis, the patient made a significant recovery.
      CONCLUSIONS: Transverse myelitis may be associated with vaccination against novel
      influenza A(H1N1). Additionally, we believe this to be the first report of
      longitudinally extensive transverse myelitis associated with any vaccine.

PMID- 20697057
TI  - Heterozygosity at polymorphic codon 219 in variant creutzfeldt-jakob disease.
AB  - BACKGROUND: Genetic variants of the prion protein gene (PRNP) strongly determine
      susceptibility to prion diseases. All tested patients with definite variant
      Creutzfeldt-Jakob disease (vCJD) are homozygous for methionine at a common
      polymorphism at codon 129. A further genetic polymorphism at codon 219, a common
      variant in several Asian populations, is considered protective against sporadic
      CJD. OBJECTIVE: To report a finding of heterozygosity at codon 219 in 2 patients
      with vCJD. DESIGN: Case reports. SETTING: MRC (Medical Research Council) Prion
      Unit and Department of Neurodegenerative Disease, University College London
      Institute of Neurology, and National Prion Clinic, National Hospital for
      Neurology and Neurosurgery. Patients Two patients with clinical and investigation
      findings consistent with the diagnoses of probable vCJD. MAIN OUTCOME MEASURES:
      Clinical and genetic findings. RESULTS: A 34-year-old man had a 15-month history
      of behavioral change progressing to ataxia, dysarthria, involuntary choreiform
      movements, and severe cognitive impairment. Cerebrospinal fluid analysis was
      positive for 14-3-3 protein, electroencephalography showed generalized slowing,
      and magnetic resonance imaging revealed thalamic high signal bilaterally, typical
      of vCJD. A 31-year-old woman had a 16-month history of cognitive decline, ataxia,
      involuntary choreiform movements, and myoclonic jerks. Magnetic resonance imaging
      showed bilateral pulvinar high signal. The diagnosis was confirmed by a tonsillar
      biopsy demonstrating abnormal prion protein deposition in a typical pattern for
      vCJD. PRNP sequencing showed a methionine homozygous codon 129 genotype and an
      E219K polymorphism in both patients. CONCLUSIONS: The E219K polymorphism is
      neutral or may even confer susceptibility to vCJD. The observations are
      interpretable in the context of the conformational selection model of prion
      replication. A barrier to prion disease transmission depends on the degree to
      which permitted pathologic conformations of the prion protein overlap between the
      inoculum and the host.

PMID- 20697058
TI  - Multiple cervical artery dissection in a volleyball player.

PMID- 20697059
TI  - Dyke-Davidoff-Masson syndrome.

PMID- 20697060
TI  - Thrombosis of a developmental venous anomaly with hemorrhagic venous infarction.

PMID- 20697061
TI  - Deep brain stimulation artifact in needle electromyography.

PMID- 20697062
TI  - Vitamin D-dependent rickets, HLA-DRB1, and the risk of multiple sclerosis.

PMID- 20697063
TI  - Evaluating retinal abnormalities in patients with multiple sclerosis.

PMID- 20697064
TI  - Apolipoprotein E epsilon4 status and cognitive decline with and without dementia.

PMID- 20697066
TI  - Role of vitamin and mineral supplementation and aspirin use in cancer survivors.
AB  - Multivitamins and multiminerals are widely used in the United States, but their
      efficacy and, perhaps more importantly, the potential for harm in individuals who
      have cancer have received relatively little study. Beyond their general effects
      on health, the use of vitamins and minerals by patients with cancer has unique
      implications because of their potential direct effects on existing cancers,
      effects on factors that may influence carcinogenesis, such as immunity, and
      interactions with treatment. Some evidence suggests that vitamin D at higher than
      standard doses may improve cancer-specific and overall survival for several
      cancer sites. Besides vitamin D, there is little evidence that nutritional
      supplements lower the risk of recurrence or improve survival from cancer,
      although some benefits may be possible in specific subgroups. Some data suggest
      that higher than standard doses of some vitamins or minerals could even enhance
      carcinogenesis or worsen survival in patients with cancer. For example, evidence
      suggests that although folate supplementation administered in preneoplastic
      stages may lower the risk of colorectal cancer, excessive folic acid in patients
      with established cancer may be harmful. For prostate cancer, some preliminary
      evidence indicates that excess consumption of one or a combination of components
      in a multivitamin/multimineral may accelerate cancer progression and increase
      fatality. Use of aspirin is proven to lower risk of colorectal cancer, and recent
      evidence suggests that aspirin use in patients with colorectal cancer improves
      cancer-specific and overall survival, especially in patients with tumors that
      express cyclooxygenase-2 (COX-2). The potential beneficial or adverse effects of
      dietary supplements and aspirin in survivors of cancer warrant further study.

PMID- 20697067
TI  - In situ vaccination with a TLR9 agonist induces systemic lymphoma regression: a
      phase I/II study.
AB  - PURPOSE: Combining tumor antigens with an immunostimulant can induce the immune
      system to specifically eliminate cancer cells. Generally, this combination is
      accomplished in an ex vivo, customized manner. In a preclinical lymphoma model,
      intratumoral injection of a Toll-like receptor 9 (TLR9) agonist induced systemic
      antitumor immunity and cured large, disseminated tumors. PATIENTS AND METHODS: We
      treated 15 patients with low-grade B-cell lymphoma using low-dose radiotherapy to
      a single tumor site and-at that same site-injected the C-G enriched, synthetic
      oligodeoxynucleotide (also referred to as CpG) TLR9 agonist PF-3512676. Clinical
      responses were assessed at distant, untreated tumor sites. Immune responses were
      evaluated by measuring T-cell activation after in vitro restimulation with
      autologous tumor cells. RESULTS: This in situ vaccination maneuver was well
      tolerated with only grade 1 to 2 local or systemic reactions and no treatment
      limiting adverse events. One patient had a complete clinical response, three
      others had partial responses, and two patients had stable but continually
      regressing disease for periods significantly longer than that achieved with prior
      therapies. Vaccination induced tumor-reactive memory CD8 T cells. Some patients'
      tumors were able to induce a suppressive, regulatory phenotype in autologous T
      cells in vitro; these patients tended to have a shorter time to disease
      progression. One clinically responding patient received a second course of
      vaccination after relapse resulting in a second, more rapid clinical response.
      CONCLUSION: In situ tumor vaccination with a TLR9 agonist induces systemic
      antilymphoma clinical responses. This maneuver is clinically feasible and does
      not require the production of a customized vaccine product.

PMID- 20697068
TI  - Genomic index of sensitivity to endocrine therapy for breast cancer.
AB  - PURPOSE: We hypothesize that measurement of gene expression related to estrogen
      receptor alpha (ER; gene name ESR1) within a breast cancer sample represents
      intrinsic tumoral sensitivity to adjuvant endocrine therapy. METHODS: A genomic
      index for sensitivity to endocrine therapy (SET) index was defined from genes
      coexpressed with ESR1 in 437 microarray profiles from newly diagnosed breast
      cancer, unrelated to treatment or outcome. The association of SET index and ESR1
      levels with distant relapse risk was evaluated from microarrays of ER-positive
      breast cancer in two cohorts who received 5 years of tamoxifen alone as adjuvant
      endocrine therapy (n = 225 and 298, respectively), a cohort who received
      neoadjuvant chemotherapy followed by tamoxifen and/or aromatase inhibition (n =
      122), and two cohorts who received no adjuvant systemic therapy (n = 208 and 133,
      respectively). RESULTS: The SET index (165 genes) was significantly associated
      with distant relapse or death risk in both tamoxifen-treated cohorts (hazard
      ratio [HR] = 0.70, 95% CI, 0.56 to 0.88, P = .002; and HR = 0.76, 95% CI, 0.63 to
      0.93, P = .007) and in the chemo-endocrine-treated cohort (HR = 0.19; 95% CI,
      0.05 to 0.69, P = .011) independently from pathologic response to chemotherapy,
      but was not prognostic in two untreated cohorts. No distant relapse or death was
      observed after tamoxifen alone if node-negative and high SET or after chemo
      endocrine therapy if intermediate or high SET. CONCLUSION: The SET index of ER
      related transcription predicted survival benefit from adjuvant endocrine therapy,
      not inherent prognosis. Prior chemotherapy seemed to enhance the efficacy of
      adjuvant endocrine therapy related to SET index.

PMID- 20697070
TI  - Is it time to ReSET the standard for estrogen receptor testing in breast cancer?

PMID- 20697069
TI  - Consolidation therapy with subcutaneous alemtuzumab after fludarabine and
      rituximab induction therapy for previously untreated chronic lymphocytic
      leukemia: final analysis of CALGB 10101.
AB  - PURPOSE: To determine if alemtuzumab consolidation improves response rate and
      progression-free survival (PFS) after induction chemoimmunotherapy in previously
      untreated symptomatic patients with chronic lymphocytic leukemia. PATIENTS AND
      METHODS: Patients (n = 102) received fludarabine 25 mg/m(2) intravenously days 1
      to 5 and rituximab 50 mg/m(2) day 1, 325 mg/m(2) day 3, and 375 mg/m(2) day 5 of
      cycle 1 and then 375 mg/m(2) day 1 of cycles 2 to 6; fludarabine plus rituximab
      (FR) administration was repeated every 28 days for six cycles. Three months after
      completion of FR, patients with stable disease or better response received
      subcutaneous alemtuzumab 3 mg day 1, 10 mg day 3, and 30 mg day 5 and then 30 mg
      three times per week for 5 weeks. RESULTS: Overall response (OR), complete
      response (CR), and partial response (PR) rates were 90%, 29%, and 61% after FR,
      respectively; 15% of patients were minimal residual disease (MRD) negative. Of
      102 patients, 58 received alemtuzumab; 28 (61%) of 46 patients achieving PR after
      FR attained CR after alemtuzumab. By intent to treat (n = 102), OR and CR rates
      were 90% and 57% after alemtuzumab, respectively; 42% of patients became MRD
      negative. With median follow-up of 36 months, median PFS was 36 months, 2-year
      PFS was 72%, and 2-year OS was 86%. In patients achieving CR after FR,
      alemtuzumab was associated with five deaths resulting from infection (viral and
      Listeria meningitis and Legionella, cytomegalovirus, and Pneumocystis
      pneumonias), which occurred up to 7 months after last therapy. The study was
      amended to exclude CR patients from receiving alemtuzumab. CONCLUSION:
      Alemtuzumab consolidation improved CR and MRD-negative rates after FR induction
      but caused serious infections in patients who had already achieved CR after
      induction and did not improve 2-year PFS or survival.

PMID- 20697071
TI  - Enhancing quality through innovation: American Society of Clinical Oncology
      presidential address 2010.

PMID- 20697072
TI  - Allogeneic hematopoietic cell transplantation for patients with mycosis fungoides
      and Sezary syndrome: a retrospective analysis of the Lymphoma Working Party of
      the European Group for Blood and Marrow Transplantation.
AB  - PURPOSE: To analyze the outcome of allogeneic transplantation for mycosis
      fungoides and Sezary syndrome (MF/SS) in terms of nonrelapse mortality (NRM),
      relapse/progression (REL), progression-free survival (PFS), and overall survival
      (OS) and to identify factors associated with the outcome. PATIENT AND METHODS:
      Sixty patients with MF (n = 36) and SS (n = 24) who received a first allogeneic
      hematopoietic cell transplantation (HCT) from a matched related (mRD; n = 45) or
      unrelated donor (mUD; n = 15) between 1997 and 2007 and who were registered in
      the European Group for Blood and Marrow Transplantation database were analyzed:
      37 men and 23 women, median age 46.5 years (range, 22 to 66 years). Forty-four
      patients had TNM stage IV, and 40 patients were at advanced phase at
      transplantation. Forty-four patients received reduced-intensity conditioning
      (RIC) regimens, and 25 underwent T-cell depletion (TCD). RESULTS: Allogeneic
      transplantation in MF/SS offers an estimated OS of 66% at 1 year and 54% at 3
      years, primarily driven by donor type, disease phase, and type of conditioning.
      RIC decreased NRM (relative risk [RR] = 4.7; P = .008) without increasing REL,
      leading to a higher OS (RR = 2.8; P = .03). Advanced-phase disease increases REL
      (RR = 3.0; P = .03) and reduces PFS (RR = 4.4; P = .002) and OS (RR = 3.5; P =
      .023). Recipients of mRD allogeneic HCT had better PFS (RR = 2.7; P = .006) and
      OS (RR = 4.0; P = .001) than their mUD counterparts. The risk of REL increases
      with TCD (RR = 3.2; P = .005). Some patients who experience relapse can
      successfully undergo rescue treatment with donor lymphocyte infusions.
      CONCLUSION: Allogeneic transplantation is a valid therapeutic alternative for
      high-risk patients with advanced-stage MF/SS. Our data also suggest the existence
      of a clinically relevant graft-versus-lymphoma effect in MF/SS.

PMID- 20697073
TI  - Active surveillance: is there a need for better risk stratification at the
      outset?

PMID- 20697074
TI  - Technology evolution: is it survival of the fittest?
AB  - New technologies are constantly being developed and introduced into medical
      practice. Their potential or actual use raises questions of efficacy and cost.
      All too often financial considerations of profit primarily determine whether a
      technology will be adopted. In an era in which the need to control costs has
      become clear, this situation is undesirable. The assessment of efficacy can,
      however, be very difficult, and the control of financial aspects is likewise
      problematic. In this article, we address these problems and suggest potential
      solutions, using proton radiotherapy as an example that may be relevant to the
      development of other medical devices.

PMID- 20697076
TI  - Harnessing innate immunity to suppress lymphoma.

PMID- 20697077
TI  - Continental Divide? The attitudes of US and Canadian oncologists on the costs,
      cost-effectiveness, and health policies associated with new cancer drugs.
AB  - PURPOSE: Oncologists in the United States and Canada work in different health
      care systems, but physicians in both countries face challenges posed by the
      rising costs of cancer drugs. We compared their attitudes regarding the costs and
      cost-effectiveness of medications and related health policy. METHODS: Survey
      responses of a random sample of 1,355 United States and 238 Canadian medical
      oncologists (all outside of Quebec) were compared. RESULTS: Response rate was
      59%. More US oncologists (67% v 52%; P < .001) favor access to effective
      treatments regardless of cost, while more Canadians favor access to effective
      treatments only if they are cost-effective (75% v 58%; P < .001). Most (84% US,
      80% Canadian) oncologists state that patient out-of-pocket costs influence their
      treatment recommendations, but less than half the respondents always or
      frequently discuss the costs of treatments with their patients. The majority of
      oncologists favor more use of cost-effectiveness data in coverage decisions (80%
      US, 69% Canadian; P = .004), but fewer than half the oncologists in both
      countries feel well equipped to use cost-effectiveness information. Majorities of
      oncologists favor government price controls (57% US, 68% Canadian; P = .01), but
      less than half favor more cost-sharing by patients (29% US, 41% Canadian; P =
      .004). Oncologists in both countries prefer to have physicians and nonprofit
      agencies determine whether drugs provide good value. CONCLUSION: Oncologists in
      the United States and Canada generally have similar attitudes regarding cancer
      drug costs, cost-effectiveness, and associated policies, despite practicing in
      different health care systems. The results support providing education to help
      oncologists in both countries use cost-effectiveness information and discuss drug
      costs with their patients.

PMID- 20697078
TI  - Tumor antigen-targeted, monoclonal antibody-based immunotherapy: clinical
      response, cellular immunity, and immunoescape.
AB  - PURPOSE: Tumor antigen (TA) -targeted monoclonal antibodies (mAb), rituximab,
      trastuzumab, and cetuximab, are clinically effective for some advanced
      malignancies, especially in conjunction with chemotherapy and/or radiotherapy.
      However, these results are only seen in a subset (20% to 30%) of patients. We
      discuss the immunologic mechanism(s) underlying these clinical findings and their
      potential role in the variability in patients' clinical response. METHODS: We
      reviewed the evidence indicating that the effects of TA-targeted mAb-based
      immunotherapy are mediated not only by inhibition of signaling pathways, but also
      by cell-mediated cytotoxicity triggered by the infused TA-targeted mAb. We
      analyzed the immunologic variables that can influence the outcome of antibody
      dependent cell-mediated cytotoxicity (ADCC) in vitro and in animal model systems.
      We also analyzed the correlation reported between these variables and the
      clinical response to mAb-based immunotherapy. RESULTS: Of the variables that
      influence ADCC mediated by TA-targeted mAb, only polymorphisms of Fcgamma
      receptors (FcgammaR) expressed by patients' lymphocytes were correlated with
      clinical efficacy. However, this correlation is not absolute and is not observed
      in all malignancies. Thus other variables may be responsible for the antitumor
      effects seen in mAb-treated patients. We discuss the evidence that triggering of
      TA-specific cellular immunity by TA-targeted mAb, in conjunction with immune
      escape mechanisms used by tumor cells, may contribute to the differential
      clinical responses to mAb-based immunotherapy. CONCLUSION: Identification of the
      mechanism(s) underlying the clinical response of patients with cancer treated
      with TA-targeted mAb is crucial to optimizing their application in the clinic and
      to selecting the patients most likely to benefit from their use.

PMID- 20697079
TI  - Prognostic significance of p16INK4A and human papillomavirus in patients with
      oropharyngeal cancer treated on TROG 02.02 phase III trial.
AB  - PURPOSE: To determine the prognostic importance of p16 and human papillomavirus
      (HPV) in patients with oropharyngeal cancer treated on a phase III concurrent
      chemoradiotherapy trial. PATIENTS AND METHODS: Patients with stage III or IV head
      and neck squamous cell cancer were randomly assigned to concurrent radiotherapy
      and cisplatin with or without tirapazamine. In this substudy, analyses were
      restricted to patients with oropharyngeal cancer. p16 was detected by
      immunohistochemistry, and HPV was detected by in situ hybridization and
      polymerase chain reaction. RESULTS: Slides were available for p16 assay in 206 of
      465 patients, of which 185 were eligible, and p16 and HPV were evaluable in 172
      patients. One hundred six (57%) of 185 were p16-positive, and in patients
      evaluable for both p16 and HPV, 88 (86%) of 102 p16-positive patients were also
      HPV-positive. Patients who were p16-positive had lower T and higher N categories
      and better Eastern Cooperative Oncology Group (ECOG) performance status. p16
      positive tumors compared with p16-negative tumors were associated with better 2
      year overall survival (91% v 74%; hazard ratio [HR], 0.36; 95% CI, 0.17 to 0.74;
      P = .004) and failure-free survival (87% v 72%; HR, 0.39; 95% CI, 0.20 to 0.74; P
      = .003). p16 was a significant prognostic factor on multivariable analysis (HR,
      0.45; 95% CI, 0.21 to 0.96; P = .04). p16-positive patients had lower rates of
      locoregional failure and deaths due to other causes. There was a trend favoring
      the tirapazamine arm for improved locoregional control in p16-negative patients
      (HR, 0.33; 95% CI, 0.09 to 1.24; P = .13). CONCLUSION: HPV-associated
      oropharyngeal cancer is a distinct entity with a favorable prognosis compared
      with HPV-negative oropharyngeal cancer when treated with cisplatin-based
      chemoradiotherapy.

PMID- 20697080
TI  - Human epidermal growth factor receptor 2 testing: where are we?

PMID- 20697081
TI  - Host factors and cancer outcome.

PMID- 20697082
TI  - Delays in adjuvant chemotherapy treatment among patients with breast cancer are
      more likely in African American and Hispanic populations: a national cohort study
      2004-2006.
AB  - PURPOSE: Previous studies have indicated poorer survival among women receiving
      adjuvant chemotherapy > 90 days after surgery compared with women receiving
      adjuvant chemotherapy within 90 days of surgery. PATIENTS AND METHODS: Women
      diagnosed between 2004 and 2006 with invasive breast cancer (stages I to III) and
      treated with surgery and adjuvant chemotherapy were selected from the National
      Cancer Database (n = 107,587). We evaluated factors associated with prolonged
      time to start adjuvant chemotherapy (>= 60 and >= 90 days after surgical
      resection) using multivariable log binomial models to estimate risk ratios (RRs)
      and 95% CIs. RESULTS: The average time to adjuvant chemotherapy was 41.46 days
      (+/- 24.46 days). Overall, 85.2% and 95.8% of women received adjuvant
      chemotherapy within 60 and 90 days of surgery, respectively. African American and
      Hispanic patients had higher risk of 60-day delay (RR, 1.36; 95% CI, 1.30 to 1.41
      and RR, 1.31; 95% CI, 1.23 to 1.39, respectively) and 90-day delay (RR, 1.56; 95%
      CI, 1.44 to 1.69 and RR, 1.41; 95% CI, 1.26 to 1.59, respectively) compared with
      white patients. Insurance type, stage, comorbidity, and facility type were also
      associated with adjuvant chemotherapy delay. CONCLUSION: The majority of women in
      our study received adjuvant chemotherapy within the time frame (90 days) for
      which there is no evidence of poorer outcome. However, the rate of delay varied
      by patient and by clinical and facility factors. Future studies on the role of
      structural, physician, clinical, and patient factors in adjuvant chemotherapy
      delay in populations of women with higher rates of delay and potential
      interventions are needed.

PMID- 20697084
TI  - HER2 and chromosome 17 effect on patient outcome in the N9831 adjuvant
      trastuzumab trial.
AB  - PURPOSE: We examined associations between tumor characteristics (human epidermal
      growth factor receptor 2 [HER2] protein expression, HER2 gene and chromosome 17
      copy number, hormone receptor status) and disease-free survival (DFS) of patients
      in the N9831 adjuvant trastuzumab trial. PATIENTS AND METHODS: All patients (N =
      1,888) underwent chemotherapy with doxorubicin and cyclophosphamide, followed by
      weekly paclitaxel with or without concurrent trastuzumab. HER2 status was
      determined by immunohistochemistry (IHC) and fluorescent in situ hybridization
      (FISH) at a central laboratory, Mayo Clinic, Rochester, MN. Patients with
      conflicting local positive HER2 expression results but normal central laboratory
      testing were included in the analyses (n = 103). RESULTS: Patients with HER2
      positive tumors (IHC 3+, FISH HER2/centromere 17 ratio >= 2.0, or both) benefited
      from trastuzumab, with hazard ratios (HRs) of 0.46, 0.49, and 0.45, respectively
      (all P < .0001). Patients with HER2-amplified tumors with polysomic (p17) or
      normal (n17) chromosome 17 copy number also benefited from trastuzumab, with HRs
      of 0.52 and 0.37, respectively (P < .006). Patients who received chemotherapy
      alone and had HER2-amplified and p17 tumors had a longer DFS than those who had
      n17 (78% v 68%; P = .04), irrespective of hormone receptor status or tumor grade.
      Patients with HER2-normal tumors by central testing (n = 103) seemed to benefit
      from trastuzumab, but the difference was not statistically significant (HR, 0.51;
      P = .14). Patients with hormone receptor-positive or -negative tumors benefited
      from the addition of trastuzumab, with HRs of 0.42 (P = .005) and 0.60 (P =
      .0001), respectively. CONCLUSION: These results confirm that IHC or FISH HER2
      testing is appropriate for patient selection for adjuvant trastuzumab therapy.
      Trastuzumab benefit seemed independent of HER2/centromere 17 ratio and chromosome
      17 copy number.

PMID- 20697085
TI  - Human epidermal growth factor receptor 2 testing in 2010: does chromosome 17
      centromere copy number make any difference?

PMID- 20697086
TI  - Fusion-negative alveolar rhabdomyosarcoma: modification of risk stratification is
      premature.

PMID- 20697089
TI  - Using lifetime risk estimates to recommend magnetic resonance imaging screening
      for breast cancer survivors.

PMID- 20697088
TI  - Energy balance, host-related factors, and cancer progression.
AB  - Obesity is associated with an increased risk and worsened prognosis for many
      types of cancer, but the mechanisms underlying the obesity-cancer progression
      link are poorly understood. Several energy balance-related host factors are known
      to influence tumor progression and/or treatment responsiveness after cancer
      develops, and these have been implicated as key contributors to the complex
      effects of obesity on cancer outcome. These host factors include leptin,
      adiponectin, steroid hormones, reactive oxygen species associated with
      inflammation, insulin, insulin-like growth factor-1, and sirtuins. Each of these
      host factors is considered in this article in the context of energy balance and
      cancer progression. In addition, future research directions in this field are
      discussed, including the importance of study designs addressing energy balance
      across the life course, the development and application of highly relevant animal
      models, potential roles of cancer stem cells in the response to energy balance
      modulation, and emerging pharmacologic approaches that target energy balance
      related pathways.

PMID- 20697090
TI  - TP53 mutation and survival in chronic lymphocytic leukemia.
AB  - PURPOSE: The precise prognostic impact of TP53 mutation and its incorporation
      into treatment algorithms in chronic lymphocytic leukemia (CLL) is unclear. We
      set out to define the impact of TP53 mutations in CLL. PATIENTS AND METHODS: We
      assessed TP53 mutations by denaturing high-performance liquid chromatography
      (exons 2 to 11) in a randomized prospective trial (n = 375) with a follow-up of
      52.8 months (German CLL Study Group CLL4 trial; fludarabine [F] v F +
      cyclophosphamide [FC]). RESULTS: We found TP53 mutations in 8.5% of patients (28
      of 328 patients). None of the patients with TP53 mutation showed a complete
      response. In patients with TP53 mutation, compared with patients without TP53
      mutation, median progression-free survival (PFS; 23.3 v 62.2 months,
      respectively) and overall survival (OS; 29.2 v 84.6 months, respectively) were
      significantly decreased (both P < .001). TP53 mutations in the absence of 17p
      deletions were found in 4.5% of patients. PFS and OS for patients with 17p
      deletion and patients with TP53 mutation in the absence of 17p deletion were
      similar. Multivariate analysis identified TP53 mutation as the strongest
      prognostic marker regarding PFS (hazard ratio [HR] = 3.8; P < .001) and OS (HR =
      7.2; P < .001). Other independent predictors of OS were IGHV mutation status (HR
      = 1.9), 11q deletion (HR = 1.9), 17p deletion (HR = 2.3), and FC treatment arm
      (HR = 0.6). CONCLUSION: CLL with TP53 mutation carries a poor prognosis
      regardless of the presence of 17p deletion when treated with F-based
      chemotherapy. Thus, TP53 mutation analysis should be incorporated into the
      evaluation of patients with CLL before treatment initiation. Patients with TP53
      mutation should be considered for alternative treatment approaches.

PMID- 20697091
TI  - International Myeloma Working Group consensus statement regarding the current
      status of allogeneic stem-cell transplantation for multiple myeloma.
AB  - PURPOSE: To define consensus statement regarding allogeneic stem-cell
      transplantation (Allo-SCT) as a treatment option for multiple myeloma (MM) on
      behalf of International Myeloma Working Group. PATIENTS AND METHODS: In this
      review, results from prospective and retrospective studies of Allo-SCT in MM are
      summarized. RESULTS: Although the introduction of reduced-intensity conditioning
      (RIC) has lowered the high treatment-related mortality associated with
      myeloablative conditioning, convincing evidence is lacking that Allo-RIC improves
      the survival compared with autologous stem-cell transplantation. CONCLUSION: New
      strategies are necessary to make Allo-SCT safer and more effective for patients
      with MM. Until this is achieved, Allo-RIC in myeloma should only be recommended
      in the context of clinical trials.

PMID- 20697092
TI  - Long-term follow-up of patients with follicular lymphoma receiving single-agent
      rituximab at two different schedules in trial SAKK 35/98.
AB  - PURPOSE: We report the long-term results of a randomized clinical trial comparing
      induction therapy with once per week for 4 weeks single-agent rituximab alone
      versus induction followed by 4 cycles of maintenance therapy every 2 months in
      patients with follicular lymphoma. PATIENTS AND METHODS: Patients (prior
      chemotherapy 138; chemotherapy-naive 64) received single-agent rituximab and if
      nonprogressive, were randomly assigned to no further treatment (observation) or
      four additional doses of rituximab given at 2-month intervals (prolonged
      exposure). RESULTS: At a median follow-up of 9.5 years and with all living
      patients having been observed for at least 5 years, the median event-free
      survival (EFS) was 13 months for the observation and 24 months for the prolonged
      exposure arm (P < .001). In the observation arm, patients without events at 8
      years were 5%, while in the prolonged exposure arm they were 27%. Of previously
      untreated patients receiving prolonged treatment after responding to rituximab
      induction, at 8 years 45% were still without event. The only favorable prognostic
      factor for EFS in a multivariate Cox regression was the prolonged rituximab
      schedule (hazard ratio, 0.59; 95% CI, 0.39 to 0.88; P = .009), whereas being
      chemotherapy naive, presenting with stage lower than IV, and showing a VV
      phenotype at position 158 of the Fc-gamma RIIIA receptor were not of independent
      prognostic value. No long-term toxicity potentially due to rituximab was
      observed. CONCLUSION: An important proportion of patients experienced long-term
      remission after prolonged exposure to rituximab, particularly if they had no
      prior treatment and responded to rituximab induction.

PMID- 20697093
TI  - Human epidermal growth factor receptor 2 assessment in a case-control study:
      comparison of fluorescence in situ hybridization and quantitative reverse
      transcription polymerase chain reaction performed by central laboratories.
AB  - PURPOSE: The optimal method to assess human epidermal growth factor receptor 2
      (HER2) status remains highly controversial. Before reporting patient HER2
      results, American Society of Clinical Oncology (ASCO)/College of American
      Pathologists (CAP) guidelines mandate that laboratories demonstrate >= 95%
      concordance to another approved laboratory or methodology. Here, we compare
      central laboratory HER2 assessed by fluorescence in situ hybridization (FISH) and
      quantitative reverse transcriptase polymerase chain reaction (RT-PCR) using
      Oncotype DX in lymph node-negative, chemotherapy-untreated patients from a large
      Kaiser Permanente case-control study. PATIENTS AND METHODS: Breast cancer
      specimens from the Kaiser-Genomic Health study were examined. Central FISH
      assessment of HER2 amplification and polysomy 17 was conducted by PhenoPath
      Laboratories (ratios > 2.2, 1.8 to 2.2, and < 1.8 define HER2 positive, HER2
      equivocal, and HER2 negative, respectively). HER2 expression by RT-PCR was
      conducted using Oncotype DX by Genomic Health (normalized expression units >=
      11.5, 10.7 to < 11.5, and < 10.7 define HER2 positive, HER2 equivocal, and HER2
      negative, respectively). Concordance analyses followed ASCO/CAP guidelines.
      RESULTS: HER2 concordance by central FISH and central RT-PCR was 97% (95% CI, 96%
      to 99%). Twelve percent (67 of 568 patients) and 11% (60 of 568 patients) of
      patients were HER2 positive by RT-PCR and FISH, respectively. HER2-positive
      patients had increased odds of dying from breast cancer compared with HER2
      negative patients. Polysomy 17 was demonstrated in 12.5% of all patients and 33%
      of FISH-positive patients. Nineteen of 20 FISH-positive patients with polysomy 17
      were also RT-PCR HER2 positive. Although not statistically significantly
      different, HER2-positive/polysomy 17 patients tended to have the worst prognosis,
      followed by HER2-positive/eusomic, HER2-negative/polysomy 17, and HER2
      negative/eusomic patients. CONCLUSION: There is a high degree of concordance
      between central FISH and quantitative RT-PCR using Oncotype DX for HER2 status,
      and the assay warrants additional study in a trastuzumab-treated population.

PMID- 20697094
TI  - Final results from a multicenter, international, pivotal study of romidepsin in
      refractory cutaneous T-cell lymphoma.
AB  - PURPOSE: The primary objective of this study was to confirm the efficacy of
      romidepsin in patients with treatment refractory cutaneous T-cell lymphoma
      (CTCL). PATIENTS AND METHODS: This international, pivotal, single-arm, open
      label, phase II study was conducted in patients with stage IB to IVA CTCL who had
      received one or more prior systemic therapies. Patients received romidepsin as an
      intravenous infusion at a dose of 14 mg/m(2) on days 1, 8, and 15 every 28 days.
      Response was determined by a composite assessment of total tumor burden including
      cutaneous disease, lymph node involvement, and blood (Sezary cells). RESULTS:
      Ninety-six patients were enrolled and received one or more doses of romidepsin.
      Most patients (71%) had advanced stage disease (>= IIB). The response rate was
      34% (primary end point), including six patients with complete response (CR).
      Twenty-six of 68 patients (38%) with advanced disease achieved a response,
      including five CRs. The median time to response was 2 months, and the median
      duration of response was 15 months. A clinically meaningful improvement in
      pruritus was observed in 28 (43%) of 65 patients, including patients who did not
      achieve an objective response. Median duration of reduction in pruritus was 6
      months. Drug-related adverse events were generally mild and consisted mainly of
      GI disturbances and asthenic conditions. Nonspecific, reversible ECG changes were
      noted in some patients. CONCLUSION: Romidepsin has significant and sustainable
      single-agent activity (including improvement in pruritus) and an acceptable
      safety profile, making it an important therapeutic option for treatment
      refractory CTCL.

PMID- 20697095
TI  - Extramedullary hematopoiesis and myeloid metaplasia of the ovaries and tubes in a
      patient with myelofibrosis: case report and concise review of the reported cases.

PMID- 20697096
TI  - p16 Expression as a predictive biomarker of hypoxic cell-sensitizing agents in
      oropharyngeal cancer.

PMID- 20697097
TI  - Circulating miRNA signatures: promising prognostic tools for cancer.

PMID- 20697098
TI  - Clinical reasoning: a 16-year-old boy with freezing of gait.

PMID- 20697099
TI  - Teaching NeuroImages: neuroimaging leads to recognition of previously undiagnosed
      Fabry disease.

PMID- 20697101
TI  - The economics of comparative effectiveness research.

PMID- 20697102
TI  - Analysis of GWAS-linked loci in Parkinson disease reaffirms PARK16 as a
      susceptibility locus.
AB  - OBJECTIVE: A genome-wide association study (GWAS) in the Japanese population
      identified 2 new Parkinson disease (PD) susceptibility loci on 1q32 (PARK16)
      (OMIM 613164) and BST1. We analyzed single nucleotide polymorphism (SNPs) located
      at the GWAS-linked loci (PARK16, PARK8, PARK1, and BST1) in a Chinese population
      and also conducted a meta-analysis in Asians by pooling 2 independent replication
      studies from Japan. METHODS: We conducted an analysis of 13 SNPs associated with
      PD GWAS-linked loci in 2 case-control cohorts comprised of 1,349 ethnic Chinese
      subjects. RESULTS: PARK16, PARK8, and PARK1 loci but not BST1 were found to be
      associated with PD. PARK16 SNPs were associated with a decreased risk while PARK1
      and PARK8 SNPs were associated with an increased risk of PD. A pooled analysis of
      our Chinese cohorts and 2 Japanese replication cohorts involving 1,366 subjects
      with PD and 16,669 controls revealed robust association with these 3 loci and
      also BST1. There was a trend toward a stronger protective effect of SNPs at the
      PARK16 locus in sporadic PD compared to familial cases and in older compared to
      younger subjects. CONCLUSIONS: Our study reaffirms the role of GWAS-linked loci
      in PD in Asian subjects and the strength of association is similar between
      Chinese and Japanese subjects. Efforts to elucidate the associated gene within
      PARK16 locus are warranted.

PMID- 20697103
TI  - Zonisamide discontinuation due to psychiatric and cognitive adverse events: a
      case-control study.
AB  - OBJECTIVES: Zonisamide (ZNS) is an antiepileptic drug (AED) that has been
      associated with psychiatric adverse events (PAE) and cognitive adverse events
      (CAE); controlled studies evaluating these adverse events are limited. Our
      objectives were to 1) determine the incidence of PAE and CAE leading to the
      discontinuation of ZNS and 2) identify risk factors for PAE and CAE associated
      with the discontinuation of ZNS. METHODS: All patients exposed to ZNS at MINCEP
      Epilepsy Care between March 2000 and September 2008 were identified. Reasons for
      discontinuing ZNS were documented. Separate case-control studies were performed
      to identify risk factors associated with the discontinuation of ZNS due to PAE or
      CAE via multivariate binary logistic regression. RESULTS: A total of 544 patients
      were exposed to ZNS during the study period. PAE and CAE were the most frequently
      identified reasons for terminating ZNS therapy. The incidence of PAE severe
      enough to be associated with the discontinuation of ZNS was 6.9%; the incidence
      of CAE was 5.8%. Factors associated with termination of ZNS therapy due to PAE
      were past psychiatric history (p = 0.005), symptomatic generalized epilepsy (p =
      0.027), and lower maximum ZNS serum concentration (mean = 17.9 mg/L vs 34.7 mg/L,
      p < 0.001). Independent variables associated with discontinuing ZNS due to CAE
      were greater number of concomitant AEDs (p = 0.011) and lower maximum ZNS serum
      concentration (mean = 16.6 mg/L vs 30.6 mg/L, p = 0.002). CONCLUSIONS: We have
      identified clinically relevant risk factors associated with the discontinuation
      of ZNS. Our findings support the concept that selected patients are relatively
      more vulnerable to CNS adverse events when exposed to ZNS.

PMID- 20697104
TI  - Assessing spinal muscular atrophy with quantitative ultrasound.
AB  - OBJECTIVE: To assess the value of quantitative ultrasound in patients with type 2
      and 3 spinal muscular atrophy (SMA). METHODS: Twenty-five patients with SMA (15
      type 2 and 10 type 3) and 21 normal subjects were enrolled for this observational
      study. Strength of biceps brachii, wrist extensors, quadriceps, and tibialis
      anterior were measured with hand-held dynamometry. In addition, these 4 muscles
      were studied with a standard ultrasound system using a 5-MHz probe, and
      luminosity values for each muscle and the overlying subcutaneous fat were
      obtained by subsequent image analysis. A luminosity ratio (LR) for each muscle
      was calculated by dividing the muscle by the subcutaneous fat luminosity. The LR
      and strength scores for all 4 muscles were averaged to provide a single summary
      value for each patient. RESULTS: The LRs increased with disease severity: 1.27 +/
      0.26 for normal subjects, 2.43 +/- 0.78 for type 3 SMA, and 3.85 +/- 1.3 for
      type 2 SMA (p < 0.001). Taking all the normal subject and patient data together,
      there was a good correlation between strength and LR (r = -0.711, p < 0.001).
      There was also a moderate relationship between LR and strength in the patients
      with SMA alone (r = -0.588, p = 0.008), and, as expected, a nonsignificant
      relationship between LR and strength in normal subjects (r = -0.011).
      CONCLUSIONS: Quantitative ultrasound has the potential of serving as a marker of
      SMA severity and may be useful in future clinical trials.

PMID- 20697105
TI  - Clinical presentations and skin denervation in amyloid neuropathy due to
      transthyretin Ala97Ser.
AB  - OBJECTIVE: Familial amyloid polyneuropathy (FAP) due to amyloidogenic
      transthyretin (TTR) is often associated with impairment of thermonociceptive
      functions. This study investigated skin innervation and its clinical significance
      in genetically defined FAP due to a hot-spot Ala97Ser TTR mutation (Ala97Ser).
      METHODS: Skin biopsies were performed on the distal leg of patients with
      Ala97Ser, and intraepidermal nerve fiber (IENF) densities were quantified.
      RESULTS: There were 19 unrelated patients with Ala97Ser manifesting a late-onset
      (59.47 +/- 5.70 years) generalized neuropathy with disabling motor, sensory, and
      autonomic symptoms. Against a background of a slowly progressive course, 7
      patients (36.8%) exhibited additional rapid declines in neurologic deficits,
      which were associated with elevation of the protein content in the CSF (p <
      0.001). The IENF density was markedly reduced in Ala97Ser patients compared to
      age- and gender-matched controls (0.99 +/- 1.11 vs 8.31 +/- 2.87 fibers/mm, p <
      0.001). Skin denervation was present in all patients and was lower in patients
      with a higher disability grade (0.17 +/- 0.26 vs 1.37 +/- 1.16 fibers/mm, p =
      0.003). Albuminocytologic dissociation in the CSF was observed in 14 patients
      (73.7%), and the IENF density was negatively correlated with the CSF protein
      concentration (p = 0.015). CONCLUSIONS: Skin denervation was common in Ala97Ser,
      and degeneration of cutaneous nerve terminals was correlated with the severity of
      clinical phenotypes and the level of CSF protein.

PMID- 20697106
TI  - Dominant spinal muscular atrophy with lower extremity predominance: linkage to
      14q32.
AB  - OBJECTIVE: Spinal muscular atrophies (SMAs) are hereditary disorders
      characterized by weakness from degeneration of spinal motor neurons. Although
      most SMA cases with proximal weakness are recessively inherited, rare families
      with dominant inheritance have been reported. We aimed to clinically,
      pathologically, and genetically characterize a large North American family with
      an autosomal dominant proximal SMA. METHODS: Affected family members underwent
      clinical and electrophysiologic evaluation. Twenty family members were genotyped
      on high-density genome-wide SNP arrays and linkage analysis was performed.
      RESULTS: Ten affected individuals (ages 7-58 years) showed prominent quadriceps
      atrophy, moderate to severe weakness of quadriceps and hip abductors, and milder
      degrees of weakness in other leg muscles. Upper extremity strength and sensation
      was normal. Leg weakness was evident from early childhood and was static or very
      slowly progressive. Electrophysiology and muscle biopsies were consistent with
      chronic denervation. SNP-based linkage analysis showed a maximum 2-point lod
      score of 5.10 (theta = 0.00) at rs17679127 on 14q32. A disease-associated
      haplotype spanning from 114 cM to the 14q telomere was identified. A single
      recombination narrowed the minimal genomic interval to Chr14: 100,220,765
      106,368,585. No segregating copy number variations were found within the disease
      interval. CONCLUSIONS: We describe a family with an early onset, autosomal
      dominant, proximal SMA with a distinctive phenotype: symptoms are limited to the
      legs and there is notable selectivity for the quadriceps. We demonstrate linkage
      to a 6.1-Mb interval on 14q32 and propose calling this disorder spinal muscular
      atrophy-lower extremity, dominant.

PMID- 20697107
TI  - Dominant-negative effects of a novel mutation in the filamin myopathy.
AB  - BACKGROUND: Filamin myopathy is associated with mutations in the filamin C gene
      (FLNC) and is a myofibrillar myopathy characterized by focal myofibrillar
      destruction and cytoplasmic aggregates containing several Z-disk-related
      proteins. METHODS: This study investigated 6 Japanese patients with dominantly
      inherited myofibrillar myopathy manifested by adult-onset, slow and progressive
      muscle weakness and atrophy in the distal extremities. RESULTS: The abundantly
      expressed proteins in the affected muscles were identified as filamin C by nano
      liquid chromatography-tandem mass spectrometry. A genetic analysis of FLNC
      identified a heterozygous c.8107delG mutation that was localized to the
      dimerization domain of filamin C. A biochemical crosslinking analysis of
      bacterially expressed recombinant wild-type and mutant filamin C fragments
      demonstrated that the mutant monomer disturbed the proper dimerization of the
      wild-type filamin dimer, resulting in formation of a heterotrimer with the wild
      type filamin dimer. The expression study in C2C12 myoblasts showed that the
      mutant filamin fragments formed cytoplasmic aggregates with endogenous wild-type
      filamin C. CONCLUSIONS: This study provides evidence for the dominant-negative
      effects of the FLNC mutation. These effects may be mutation-specific and likely
      result in the variation in the clinical phenotypes seen in patients with filamin
      myopathy.

PMID- 20697108
TI  - Pretreatment ASPECTS on DWI predicts 3-month outcome following rt-PA: SAMURAI rt
      PA Registry.
AB  - OBJECTIVE: To evaluate whether the pretreatment Alberta Stroke Programme Early CT
      Score (ASPECTS) assessed using diffusion-weighted imaging (DWI) predicts stroke
      outcomes at 3 months following IV recombinant tissue-type plasminogen activator
      (rt-PA) therapy. METHODS: Stroke patients treated with rt-PA (0.6 mg/kg
      alteplase) in 10 stroke centers in Japan were retrospectively studied. ASPECTS
      was assessed on DWI just prior to rt-PA injection. The primary outcome was a
      modified Rankin Scale (mRS) score of 0-2 at 3 months. Secondary outcomes included
      death at 3 months and symptomatic intracerebral hemorrhage (sICH) within 36
      hours. RESULTS: For the 477 patients (316 men, 71 +/- 11 years old) enrolled, the
      median NIH Stroke Scale score was 13 (interquartile range 7-18.5), the median
      ASPECTS on DWI was 8 (7-10), and sICH was identified in 15 patients (3.1%). At 3
      months, 245 (51.4%) had an mRS score of 0-2, and 29 (6.1%) had died. Patients
      with an mRS score of 0-2 had higher median ASPECTS (9; interquartile range 8-10)
      than other patients (8; 6-9, p < 0.001). Using receiver operating characteristic
      curves, the optimal cutoff ASPECTS to predict an mRS score of 0-2 was > or =7. On
      multivariate regression analysis, ASPECTS > or =7 was related to an mRS score of
      0-2 (odds ratio 1.85; 95% confidence interval 1.07-3.24), ASPECTS < or =4 was
      related to death (3.61; 1.23-9.91), and ASPECTS < or =5 was related to sICH
      (4.74; 1.54-13.64). CONCLUSION: ASPECTS on DWI was independently predictive of
      functional and vital outcomes at 3 months, as well as sICH within 36 hours,
      following rt-PA therapy for stroke patients.

PMID- 20697109
TI  - Invited article: comparative effectiveness research, evidence-based medicine, and
      the AAN.
AB  - Comparative effectiveness research (CER) is the study of the relative effects of
      treatments to determine which will be most likely to improve overall health for a
      specific condition. This area has received a great deal of political focus, and
      substantial funding for CER is included in the American Reinvestment and Recovery
      Act of 2009. The results of CER are intended to inform evidence-based guidelines
      and to improve the quality and effectiveness of medical care. In the absence of
      such research, guidelines often depend on consensus to rank available therapies.
      We believe that an increase in CER would clearly enhance evidence-based
      guidelines. However, the research must be performed and analyzed with great care
      to avoid reaching unhelpful, or even harmful, conclusions. Specifically,
      individual patient characteristics must be taken into account, study endpoints
      must approximate the most important patient outcomes, therapies must be used
      optimally within the studies, and the most relevant therapies for a given
      indication must be included for comparison. CER that is not performed or
      interpreted correctly could have the potential to affect negatively our choices
      of therapies. The neurology community must help inform the process of CER to
      ensure the highest-quality research, which in turn will result in the most valid
      outcomes.

PMID- 20697110
TI  - A case of neurosarcoidosis successfully treated with rituximab.

PMID- 20697111
TI  - Reflections: neurology and the humanities. Description of a family with progeria
      by Charles Dickens.

PMID- 20697112
TI  - Hypertensive cerebral hemorrhage: imaging the leak with 7-T MRI.

PMID- 20697113
TI  - Smoking duration, intensity, and risk of Parkinson disease.

PMID- 20697114
TI  - Does hypothermia influence the predictive value of bilateral absent N20 after
      cardiac arrest?

PMID- 20697115
TI  - Incidentally detected gallbladder polyps: is follow-up necessary?--Long-term
      clinical and US analysis of 346 patients.
AB  - PURPOSE: To determine the natural history of gallbladder (GB) polyps incidentally
      detected at ultrasonography (US) and to propose management guidelines for these
      lesions based on polyp size. MATERIALS AND METHODS: The HIPAA-compliant study was
      approved by the institutional review board, and informed consent was waived. A
      database search for "polyp" in all US examinations of the GB between January 1,
      1999, and December 31, 2001, at a single institution was performed. All
      subsequent US reports were reviewed to determine changes in GB polyp size. The
      electronic medical record was searched to obtain clinical and pathologic follow
      up. RESULTS: Three hundred forty-six patients (mean age, 51.6 years; range, 20-93
      years) with GB polyps were included. There were 156 men (45%) and 190 women
      (55%). US follow-up (mean, 5.4 years; range, 2-11.5 years) was performed in 149
      patients (43%). Polyp size was stable in 90 (60%) polyps, decreased in eight
      (5%), increased in one (1%), and resolved in 50 (34%). Forty-two patients (12%)
      underwent cholecystectomy, revealing 13 (31%) GBs with polypoid lesions, 24 (57%)
      with stones and no polyps, and five (12%) with neither a stone nor a polypoid
      lesion. Clinical follow-up (mean, 8 years; range, 5-10.4 years) was performed in
      155 patients (45%). No patient had clinical evidence of GB-related disease.
      Overall, no cases of GB malignancy were identified in 346 patients. Mean polyp
      size was 5.0 mm (range, 1-18 mm). No neoplastic polyps were found at 1-6 mm, one
      neoplastic polyp was seen at 7-9 mm, and two neoplastic polyps were found at 10
      mm or larger. CONCLUSION: The risk of GB malignancy resulting from incidentally
      detected polyps is extremely low. Incidentally detected GB polyps measuring 6 mm
      or less may require no additional follow-up. Data are inconclusive regarding
      polyps 7 mm or greater, and further studies are warranted.

PMID- 20697116
TI  - Recurrent ovarian cancer: use of contrast-enhanced CT and PET/CT to accurately
      localize tumor recurrence and to predict patients' survival.
AB  - PURPOSE: To compare accuracy and interobserver variability in the detection and
      localization of recurrent ovarian cancer with contrast material-enhanced (CE)
      computed tomography (CT) and positron emission tomography (PET)/CT and determine
      whether imaging findings can be used to predict survival. MATERIALS AND METHODS:
      Waiving informed consent, the institutional review board approved this HIPAA
      compliant, retrospective study of 35 women (median age, 54.4 years) with
      histopathologically proven recurrent ovarian carcinoma who underwent CE CT and
      PET/CT before exploratory surgery. All CE CT and PET/CT scans were independently
      analyzed. Tumor presence, number of lesions, and the size and maximum
      standardized uptake value (SUV(max)) of the largest lesion were recorded for
      patient and region. Surgical histopathologic findings constituted the reference
      standard. Areas under the receiver operating characteristic curves (AUCs), kappa
      statistics, and hazard ratios were calculated. RESULTS: Readers' AUCs in
      detection of recurrence for region were 0.85 (95% confidence interval [CI]: 0.81,
      0.90) and 0.78 (95% CI: 0.72, 0.83) for CE CT and 0.84 (95% CI: 0.79, 0.89) and
      0.74 (95% CI: 0.67, 0.81) for PET/CT (P = .76); 12 patients died. At PET/CT,
      size, number, and SUV(max) of peritoneal deposits were significantly associated
      with poor survival for readers 1 and 2 (P <= .01and <= .05, respectively), as
      were long- and short-axis diameters, number, and SUV(max) of distant lymph nodes
      for reader 1 (P <= .001). With CE CT, size (reader 1) and number (readers 1 and
      3) of peritoneal deposits were significantly associated with poor survival (P <=
      .01), as were long- and short-axis diameters and number of distant lymph nodes
      for reader 1 (P <= .01). Interobserver agreement ranged from fair (patient, kappa
      = 0.30) to moderate (region, kappa = 0.55) for CE CT and fair (patient, kappa =
      0.24) to substantial (region, kappa = 0.63) for PET/CT. CONCLUSION: Preliminary
      data suggest that CE CT and PET/CT may have similar accuracy in detection of
      recurrent ovarian cancer. Tumor size, number, and SUV(max) may have potential as
      prognostic biomarkers for patients with recurrent ovarian cancer.

PMID- 20697117
TI  - Ligaments and plicae of the elbow: normal MR imaging variability in 60
      asymptomatic subjects.
AB  - PURPOSE: To prospectively evaluate the normal variability of ligaments, plicae,
      and the posterior capitellum on conventional magnetic resonance (MR) images of
      the elbow in asymptomatic volunteers. MATERIALS AND METHODS: The study was
      approved by the institutional ethics board, and informed consent was obtained
      from all subjects. MR imaging was performed at 1.5 T in 60 asymptomatic
      volunteers (30 women, 30 men; age range, 22-51 years; median age, 32.8 years) by
      using the following five pulse sequences: transverse T1-weighted spin-echo,
      sagittal T2-weighted fast spin-echo, coronal fast spin-echo short-inversion-time
      inversion recovery, transverse intermediate-weighted with fat saturation, and
      coronal three-dimensional water-excitation true fast imaging with steady-state
      precession. The visibility (completely visible over the entire course, partially
      visible, or not visible) and signal intensity characteristics (hypointense or
      hyperintense to muscle, homogeneous signal intensity vs striation) of the elbow
      ligaments and plicae were evaluated by three independent readers. The presence of
      pseudodefects at the posterior capitellum was determined. The dimensions of all
      structures were measured by two independent readers. RESULTS: The anterior ulnar
      collateral ligament (UCL) and radial collateral ligament (RCL) were visible over
      their entire course in all 60 subjects (100%). The posterior UCL, lateral UCL,
      and annular ligament (AL) were completely visible in 58 (97%), 51 (85%), and 59
      (98%) of the 60 subjects, respectively, and partially visible in the remaining
      subjects. Increased signal intensity with fluid-sensitive sequences was found in
      the anterior UCL in nine of the 60 subjects (15%), posterior UCL in four subjects
      (7%), RCL in one subject (2%), lateral UCL in six subjects (10%), and AL in one
      subject (2%). The median thickness and 90th percentile were 2.5 and 3.5 mm,
      respectively, for the anterior UCL, 1.0 and 1.7 mm for the posterior UCL, 1.9 and
      2.8 mm for the RCL, 2.3 and 3.8 mm for the lateral UCL, and 1.0 and 1.3 mm for
      the AL. A posterolateral plica (median dimension, 4.3 * 1.9 * 3.9 mm) was found
      in 59 of the 60 subjects (98%), whereas a posterior plica (median dimension, 1.8
      * 1.4 mm) could be detected in only 20 (33%). A pseudodefect of the capitellum
      was noted in 51 of the 60 subjects (85%). CONCLUSION: The elbow ligaments and the
      posterolateral plica are consistently visible on conventional MR images of
      asymptomatic subjects. Most normal ligaments are thinner than 4 mm, and most
      plicae are thinner than 3 mm.

PMID- 20697118
TI  - Visually isoattenuating pancreatic adenocarcinoma at dynamic-enhanced CT:
      frequency, clinical and pathologic characteristics, and diagnosis at imaging
      examinations.
AB  - PURPOSE: To retrospectively determine the frequency, clinical and pathologic
      characteristics, and computed tomographic (CT) findings of visually
      isoattenuating pancreatic adenocarcinomas and to investigate the utility of
      magnetic resonance (MR) imaging and positron emission tomography (PET)/CT for
      detecting them. MATERIALS AND METHODS: Institutional review board approval was
      obtained. Patient informed consent was waived. Of 743 consecutive patients with
      pathologically proved pancreatic cancer, 644 patients (392 men, 252 women; mean
      age, 60 years +/- 9.5 [standard deviation]) who had undergone both arterial and
      portal phase contrast material-enhanced CT were included. Visually isoattenuating
      pancreatic adenocarcinoma was defined as lesion isoattenuation in both scan
      phases. Serum levels of carbohydrate antigen 19-9, immunoglobulin G (IgG), and
      IgG fraction 4 (IgG4), survival after curative-intent surgery; and pathologic
      findings of visually isoattenuating pancreatic adenocarcinomas were analyzed. CT
      findings of visually isoattenuating pancreatic adenocarcinomas and the
      sensitivity of MR imaging and PET/CT for detecting them were determined. RESULTS:
      The frequency of visually isoattenuating pancreatic adenocarcinomas among
      pancreatic cancers was 5.4% (35 of 644). Serum levels of carbohydrate antigen 19
      9, IgG, and IgG4 were elevated in 51.5% (17 of 33), 8.3% (one of 12), and 8.3%
      (one of 12) of patients, respectively. Visually isoattenuating pancreatic
      adenocarcinoma, compared with usual pancreatic adenocarcinoma, was independently
      associated with a better survival after curative-intent surgery: Adjusted hazard
      ratio was 0.430 (P = .006). Thirty surgically resected visually isoattenuating
      pancreatic adenocarcinomas were 1.5-4 cm (median, 3 cm). Their pathologic
      findings differed from those of usual pancreatic adenocarcinomas: lower tumor
      cellularity, more frequent intratumoral acinar tissue and islet cells, and less
      prominent tumor necrosis. Visually isoattenuating pancreatic adenocarcinomas
      showed various abnormalities at CT, which may suggest an isoattenuating mass or
      nodule. Sensitivities of MR imaging and PET/CT were 79.2% (19 of 24) and 73.7%
      (14 of 19), respectively. CONCLUSION: Visually isoattenuating pancreatic
      adenocarcinoma represents a small but meaningful subset of pancreatic cancer and
      has characteristic clinical and pathologic features. MR imaging and PET/CT may be
      useful as subsequent examinations when the patient is suspected of having the
      lesion at CT.

PMID- 20697119
TI  - Prognostic value and staging categories of anatomic masticator space involvement
      in nasopharyngeal carcinoma: a study of 924 cases with MR imaging.
AB  - PURPOSE: To identify the prognostic value and staging categories of masticator
      space involvement in nasopharyngeal carcinoma (NPC) as determined with anatomic
      criteria ("anatomic masticator space involvement") to determine whether it is
      necessary for the masticator space described with criteria of the American Joint
      Committee on Cancer to exclude the medial and lateral pterygoid muscles.
      MATERIALS AND METHODS: This retrospective study was approved by the institutional
      review board, and the requirement to obtain informed consent was waived. NPC was
      diagnosed in 924 patients with magnetic resonance (MR) imaging, and medical
      records and imaging studies were retrospectively analyzed. The overall survival,
      local relapse-free survival, and distant metastasis-free survival of these
      patients were analyzed by using the Kaplan-Meier method; differences were
      compared by using the log-rank test. RESULTS: The frequency of anatomic
      masticator space involvement was 19.7% (182 of 924 patients). With use of
      multivariate analysis, anatomic masticator space involvement was identified as an
      independent prognostic factor for overall survival (P = .02). In addition,
      anatomic masticator space involvement was associated with a marginally
      significant decrease in local relapse-free survival (P = .05); however, it had no
      effect on distant metastasis-free survival. There were no statistically
      significant differences between different degrees of anatomic masticator space
      involvement with regard to overall survival and local relapse-free survival in
      NPC (P = .34 and P = .54, respectively) or between T3 or T4 disease and anatomic
      masticator space involvement with regard to overall survival and local relapse
      free survival (P = .63 and P = .44, respectively). CONCLUSION: Anatomic
      masticator space involvement affects the overall survival and local relapse-free
      survival of patients with NPC. When masticator space involvement includes the
      medial and lateral pterygoid muscles, the disease should be classified as stage
      T4.

PMID- 20697120
TI  - Caudate lobe hepatocellular carcinoma treated with selective chemoembolization.
AB  - PURPOSE: To analyze the clinical outcomes of chemoembolization for solitary
      caudate lobe hepatocellular carcinoma (HCC) found at initial presentation.
      MATERIALS AND METHODS: This retrospective study was approved by the institutional
      review board; the requirement for informed patient consent was waived. From July
      1998 to June 2009, 40 patients (28 men, 12 women; mean age, 57 years) found to
      have a single HCC lesion in the caudate lobe at initial presentation were treated
      with chemoembolization and evaluated for overall survival and progression-free
      survival. Multivariate analyses for potential clinical and radiologic factors
      were performed by using the Cox proportional hazard model. RESULTS: Selective
      chemoembolization via the caudate artery was achieved in 34 (85%) patients.
      Overall survival rates at 1, 2, 3, 4, and 5 years were 92%, 79%, 65%, 56%, and
      56%, respectively. Selective chemoembolization of the caudate artery was a
      critically important factor in longer overall survival (hazard ratio, 0.091; 95%
      confidence interval [CI]: 0.021, 0.389; P < .001), and portal vein tumor
      thrombosis (hazard ratio, 31.25; 95% CI: 4.88, 200.1; P < .001) and multiple
      tumor-feeding vessels (hazard ratio, 6.87; 95% CI: 1.47, 32.1; P = .014) were
      significant factors in shorter overall survival. Selective chemoembolization of
      the caudate artery was also a significant factor in longer progression-free
      survival (hazard ratio, 0.278; 95% CI: 0.10, 0.76; P = .013). CONCLUSION:
      Selective chemoembolization via the caudate artery is possible in most patients
      with caudate lobe HCC and a critical factor in longer overall survival and longer
      progression-free survival.

PMID- 20697121
TI  - Meiotic chromosome segregation in triploid strains of Saccharomyces cerevisiae.
AB  - Meiosis in triploids results in four highly aneuploid gametes because six copies
      of each homolog must be segregated into four meiotic products. Using DNA
      microarrays and other physical approaches, we examined meiotic chromosome
      segregation in triploid strains of Saccharomyces cerevisiae. In most tetrads with
      four viable spores, two of the spores had two copies of a given homolog and two
      spores had only one copy. Chromosomes segregated randomly into viable spores
      without preferences for generating near haploid or near diploid spores. Using
      single-nucleotide polymorphisms, we showed that, in most tetrads, all three pairs
      of homologs recombined. Strains derived from some of the aneuploid spore colonies
      had very high frequencies of mitotic chromosome loss, resulting in genetically
      diverse populations of cells.

PMID- 20697122
TI  - c-type cytochrome assembly in Saccharomyces cerevisiae: a key residue for
      apocytochrome c1/lyase interaction.
AB  - The electron transport chains in the membranes of bacteria and organelles
      generate proton-motive force essential for ATP production. The c-type
      cytochromes, defined by the covalent attachment of heme to a CXXCH motif, are key
      electron carriers in these energy-transducing membranes. In mitochondria,
      cytochromes c and c(1) are assembled by the cytochrome c heme lyases (CCHL and
      CC(1)HL) and by Cyc2p, a putative redox protein. A cytochrome c(1) mutant with a
      CAPCH heme-binding site instead of the wild-type CAACH is strictly dependent upon
      Cyc2p for assembly. In this context, we found that overexpression of CC(1)HL, as
      well as mutations of the proline in the CAPCH site to H, L, S, or T residues, can
      bypass the absence of Cyc2p. The P mutation was postulated to shift the CXXCH
      motif to an oxidized form, which must be reduced in a Cyc2p-dependent reaction
      before heme ligation. However, measurement of the redox midpoint potential of
      apocytochrome c(1) indicates that neither the P nor the T residues impact the
      thermodynamic propensity of the CXXCH motif to occur in a disulfide vs. dithiol
      form. We show instead that the identity of the second intervening residue in the
      CXXCH motif is key in determining the CCHL-dependent vs. CC(1)HL-dependent
      assembly of holocytochrome c(1). We also provide evidence that Cyc2p is dedicated
      to the CCHL pathway and is not required for the CC(1)HL-dependent assembly of
      cytochrome c(1).

PMID- 20697125
TI  - Modification and implementation of NCCN guidelines on non-small cell lung cancer
      in the Middle East and North Africa region.
AB  - A lung cancer committee from the Middle East and North Africa (MENA) region was
      established to modify the NCCN Clinical Practice Guidelines in Oncology (NCCN
      Guidelines) on Non-Small Cell Lung Cancer to create a platform for standard care
      in the region. The committee comprised different experts in thoracic oncology
      from the region, including the disciplines of medical and clinical oncology,
      radiation oncology, thoracic surgery, pulmonary medicine, radiology, and
      pathology. The committee reviewed version 2 of the 2009 NCCN Guidelines on Non
      Small Cell Lung Cancer and identified recommendations requiring modification for
      the region using published evidence and relevant experience. These suggested
      modifications were discussed among the group and with a United States-based NCCN
      expert for approval. The recommended modifications, with justification and
      references, were categorized based on the NCCN Guidelines flow. This article
      describes these recommended modifications. The process of adapting the first NCCN
      based guidelines in the region is a step toward helping to improve lung cancer
      care in the region and encouraging networking and collaboration.

PMID- 20697123
TI  - Refinement of tools for targeted gene expression in Drosophila.
AB  - A wide variety of biological experiments rely on the ability to express an
      exogenous gene in a transgenic animal at a defined level and in a spatially and
      temporally controlled pattern. We describe major improvements of the methods
      available for achieving this objective in Drosophila melanogaster. We have
      systematically varied core promoters, UTRs, operator sequences, and
      transcriptional activating domains used to direct gene expression with the GAL4,
      LexA, and Split GAL4 transcription factors and the GAL80 transcriptional
      repressor. The use of site-specific integration allowed us to make quantitative
      comparisons between different constructs inserted at the same genomic location.
      We also characterized a set of PhiC31 integration sites for their ability to
      support transgene expression of both drivers and responders in the nervous
      system. The increased strength and reliability of these optimized reagents
      overcome many of the previous limitations of these methods and will facilitate
      genetic manipulations of greater complexity and sophistication.

PMID- 20697126
TI  - The Abu Dhabi declaration: why the hustle?

PMID- 20697127
TI  - Modification and implementation of NCCN guidelines on colon cancer in the Middle
      East and North Africa region.
AB  - Colorectal cancer is less common in the Middle East and South Asia than in
      western countries, with the rectum the most common primary site, unlike in the
      United States. A project was planned to address various local issues regarding
      the management of common cancers, including colorectal cancer, and to adapt the
      NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) to the Middle
      East and North Africa (MENA) region. A survey of oncologists in this geographic
      area showed that the management practices and issues regarding colorectal cancer
      are similar to those presented in the NCCN Colorectal Cancer Guidelines. However,
      2 major differences exist: most oncologists in the MENA region prefer chest
      radiograph over CT in pretreatment workup, and almost 50% of them prefer to use
      cetuximab in the first-line treatment of patients with the wild-type KRAS gene.
      The committee, comprising 9 oncologists from different countries, proposed 4
      modifications to the 2009 version of the NCCN Colorectal Cancer Guidelines for
      use in the MENA region, relating to 1) short-course preoperative radiotherapy, 2)
      dose of capecitabine, 3) stereotactic radiotherapy for liver metastasis, and 4)
      qualification of surgeons performing colorectal surgery. The modification of NCCN
      Colorectal Cancer Guidelines for use in the MENA region represents a step toward
      creating a uniform practice in the region based on evidence and local experience.

PMID- 20697128
TI  - Modification and implementation of NCCN guidelines on prostate cancer in the
      Middle East and North Africa region.
AB  - A prostate cancer committee was established to modify the NCCN Clinical Practice
      Guidelines in Oncology (NCCN Guidelines) on Prostate Cancer for adaptation and
      implementation in the Middle East and North Africa (MENA) region. The objective
      was to enhance the multidisciplinary approach to the treatment of prostate
      cancer. The committee, comprising regional experts in the fields of urologic,
      medical, and radiation oncology, reviewed the 2009 version of the NCCN Guidelines
      on Prostate Cancer and suggested modifications based on the unique needs of the
      regions determined through published evidence and local expertise. The committee
      identified several areas in the NCCN Guidelines that they believed required
      modification, which are presented in this article. The treatment of prostate
      cancer in the MENA region has numerous challenges. The hope is that this effort
      to modify the NCCN Guidelines on Prostate Cancer for practical use in the MENA
      region will improve regional awareness and patient care.

PMID- 20697129
TI  - Modification and implementation of NCCN guidelines on lymphomas in the Middle
      East and North Africa region.
AB  - In the Middle East and North Africa (MENA) region, cancer has many epidemiologic
      and clinical features that are different from those in the rest of the world.
      Additionally, the region has a relatively young population and large disparities
      in the availability of resources at diagnostic and treatment levels. A critical
      need exists for regional guidelines on cancer care, including those for lymphoid
      malignancies. A panel of lymphoma experts from MENA reviewed the 2009 version of
      the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) on Non
      Hodgkin's Lymphoma and Hodgkin Lymphoma and suggested modifications for the
      region that were discussed with the United States NCCN Lymphoma Panels. This
      article presents the consensus recommendations.

PMID- 20697130
TI  - Modification and implementation of NCCN guidelines on hepatobiliary cancers in
      the Middle East and North Africa region.
AB  - The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) on
      Hepatobiliary Cancers address hepatocellular cancer, cancer of the gallbladder,
      extrahepatic cholangiocarcinoma, and intrahepatic cholangiocarcinoma.
      Hepatocellular cancer incidence is higher in the Middle East and North Africa
      (MENA) region than in the West, and hepatitis B and C infections are particularly
      important; the incidence of gallbladder cancer is among the highest in the world.
      Regional problems include delay in diagnosis, shortage of trained staff, and
      insufficient liver transplant facilities. Furthermore, costs associated with
      molecular and targeted therapies are an increasing concern. A committee was
      formed, consisting of leading specialists and decision-makers from the region,
      with each member being tasked to suggest modifications to the existing guidelines
      based on review of the literature and consultations with local colleagues. This
      committee met as a group, and then continued to discuss and debate the suggested
      modifications electronically. Several recommendations were finalized after
      vigorous debate. The final approved recommendations were then presented in April
      2009 to the chair of the NCCN Hepatobiliary Cancers Panel for onward transmission
      and approval. This project represents an effort to modify and implement the NCCN
      Guidelines on Hepatobiliary Cancers in the MENA region, while taking into
      consideration local differences in patient and disease characteristics. The hope
      is that this will form the basis of future local, regional, and international
      cooperation in guideline development and research.

PMID- 20697131
TI  - Modification and implementation of NCCN Guidelines on palliative care in the
      Middle East and North Africa region.
AB  - Palliative care is an important component of cancer treatment. Advancing
      palliative care in the developing countries is essential to improving patient
      care. The issues limiting its practice must be addressed, especially in light of
      the initiative to adapt the NCCN Clinical Practice Guidelines in Oncology (NCCN
      Guidelines) to the Middle East and North Africa (MENA) region. Palliative care is
      in its early stage of evolution in the MENA region, and its practice encounters
      many challenges and barriers. Adaptation of guidelines should take into
      consideration the situation and conditions in the targeted region to improve the
      standard of care to an internationally acceptable level. A group of experts in
      the MENA region reviewed the literature and collaborated to assess the current
      status of palliative care and recommend modifications to the NCCN Guidelines
      based on the unique needs of the region.

PMID- 20697132
TI  - The process of NCCN guidelines adaptation to the Middle East and North Africa
      region.
AB  - The NCCN developed clinical practice guidelines for oncology that set the
      standard of cancer care in the United States. Because of wide acceptance of, need
      for, and interest in standardized treatment practices across the world, NCCN
      launched initiatives to help international groups adapt these guidelines. This
      article describes the initiative in the Middle East and North Africa (MENA)
      region. A group of oncology experts and key opinion leaders were assembled into 7
      specific committees to develop treatment guidelines for breast cancer, lung
      cancer, colon cancer, prostate cancer, hepatobiliary cancer, lymphoma, and
      palliative care. The committees reviewed the NCCN Clinical Practice Guidelines in
      Oncology (NCCN Guidelines) to identify any modifications required for them to be
      more applicable to the MENA region based on available evidence and regional
      experience. These modifications were discussed with NCCN experts and summarized
      for each specific area. The development of these guidelines generated a strong
      interest in the region to develop more evidence-based practice and create further
      networking and collaboration.

PMID- 20697133
TI  - Modification and implementation of NCCN guidelines on breast cancer in the Middle
      East and North Africa region.
AB  - Published data from the Middle East and North Africa (MENA) region indicate
      suboptimal quality of cancer care, while the World Health Organization predicts
      an increase in cancer cases in developing countries. Major advances in breast
      cancer management mandate the development of guidelines to improve the quality
      and efficacy of oncology practice in the MENA region. A Breast Cancer Regional
      Guidelines Committee was organized and activated, comprising experts from various
      regional cancer institutions. The multidisciplinary team included 12 medical
      oncologists, 3 radiation oncologists, 2 radiologists, 2 surgeons, and 1
      pathologist. The committee members agreed on adapting the current NCCN Clinical
      Practice Guidelines in Oncology (NCCN Guidelines) on Breast Cancer for use in the
      MENA region to achieve common practice standards for treating patients. The
      members suggested several modifications to the guidelines, especially those
      related to risk factor profiles. United States-based NCCN experts reviewed these
      recommendations before final approval. The MENA-NCCN Breast Cancer Guidelines
      modification process was the first initiative in the development of common
      practice guidelines in the region. This project may serve as a foundation for the
      development of evidence-based practice standards, and improve collaborative
      projects and initiatives.

PMID- 20697134
TI  - Counterpoint: Left ventricular volume during diastasis is not the physiological
      in vivo equilibrium volume and is not related to diastolic suction.

PMID- 20697135
TI  - Rebuttal from Yellin and Nikolic. Left ventricular volume during diastasis is not
      the physiological in vivo equilibrium volume and is not related to diastolic
      suction.

PMID- 20697136
TI  - Rebuttal from Shmuylovich, Chung, and Kovacs. Left ventricular volume during
      diastasis is not the physiological in vivo equilibrium volume and is not related
      to diastolic suction.

PMID- 20697137
TI  - Comments on Point: Counterpoint: Left ventricular volume during diastasis is/is
      not the physiological in vivo equilibrium volume and is/is not related to
      diastolic suction.

PMID- 20697138
TI  - Last word on point: Counterpoint: Left ventricular volume during diastasis is the
      physiological in vivo equilibrium volume and is related to diastolic suction.

PMID- 20697139
TI  - Last word on point: Counterpoint: Left ventricular volume during diastasis is not
      the physiological in vivo equilibrium volume and is not related to diastolic
      suction.

PMID- 20697140
TI  - Intergenic transposable elements are not randomly distributed in bacteria.
AB  - Insertion sequences (ISs) are mobile genetic elements in bacterial genomes. In
      general, intergenic IS elements are probably less deleterious for their hosts
      than intragenic ISs, simply because they have a lower likelihood of disrupting
      native genes. However, since promoters, Shine-Dalgarno sequences, and
      transcription factor binding sites are intergenic and upstream of genes, I
      hypothesized that not all neighboring gene orientations (NGOs) are selectively
      equivalent for IS insertion. To test this, I analyzed the NGOs of all intergenic
      ISs in 326 fully sequenced bacterial chromosomes. Of the 116 genomes with enough
      IS elements for statistical analysis, 68 have significantly more ISs between
      convergently oriented genes than expected, and 46 have significantly fewer ISs
      between divergently oriented genes. This suggests that natural selection molds
      intergenic IS distributions because they are least intrusive between convergent
      gene pairs and most intrusive between divergent gene pairs.

PMID- 20697141
TI  - Follicular fluid-specific distribution of vascular endothelial growth factor
      isoforms and sFlt-1 in patients undergoing IVF and their correlation with
      treatment outcomes.
AB  - OBJECTIVE: To investigate the distribution of vascular endothelial growth factor
      (VEGF) isoforms and soluble form of VEGF receptor 1 (sFlt-1) in the follicular
      fluid (FF) of in vitro fertilization (IVF) patients in relationship to age, body
      mass index (BMI), diagnosis of polycystic ovary syndrome (PCOS), and their
      correlation with IVF outcomes. DESIGN: Prospective study. MAIN OUTCOME MEASURES:
      VEGF( 121) and VEGF(165) isoforms were detected using Western blotting and pixel
      density analysis. The concentration of sFlt-1 was determined by enzyme-linked
      immunosorbent assay (ELISA). In vitro fertilization outcomes measured included
      number of oocytes retrieved, fertilization rate, and clinical pregnancy.
      Statistical analysis used the Kruskal-Wallis and Mann-Whitney U test where
      appropriate. RESULTS: There was a statistically significant association between
      higher VEGF(165) levels and the diagnosis of PCOS, BMI >= 30, and age >=40 years.
      In vitro fertilization cycles resulting in pregnancy were linked to statistically
      lower VEGF(165) levels in the FF. No statistically significant trend was
      identified in levels of VEGF(121) or sFlt-1 relative to patient characteristics
      or IVF outcomes. CONCLUSION: Our results suggest that elevated VEGF(165) levels
      are associated with less favorable patient characteristics and clinical IVF
      outcomes.

PMID- 20697142
TI  - Promoter hypermethylation of progesterone receptor isoform B (PR-B) in
      adenomyosis and its rectification by a histone deacetylase inhibitor and a
      demethylation agent.
AB  - Adenomyosis is a fairly common gynecologic disease with unknown pathogenesis. We
      sought to investigate as to whether the promoter of progesterone receptor isoform
      B (PR-B) is hypermethylated in adenomyosis and to investigate the treatment of
      ectopic endometrial stromal cells with trichostatin A (TSA), a histone
      deacetylase inhibitor (HDI), and 5-aza-2-deoxycytidine (ADC), a demethylation
      agent, on PR-B gene and protein expression, and on cell viability. Ectopic
      endometrial tissue specimens were obtained from 9 women with adenomyosis whereas
      control endometrial tissue samples were obtained from 8 women with surgically
      diagnosed benign ovarian cysts but without any clinical history of
      endometriosis/adenomyosis/ myoma. Endometrial stromal cells were isolated,
      purified, cultured, and analyzed by methylation-specific polymerase chain
      reaction (PCR), real-time reverse transcriptase PCR (RT-PCR), and Western blot
      analysis, cell viability assays, and fluorescence-activated cell sorting. We
      found that none of the normal endometrial stromal cells had PR-B promoter
      methylation. In contrast, 2 out of 3 ectopic endometrial stromall cells had PR-B
      hypermethylation (P < .05). The treatment with both TSA and ADC elevated PR-B
      gene and protein expression in ectopic, but not in normal, endometrial stromal
      cells. Both TSA and ADC treatment dose-dependently reduced cell viability of
      ectopic endometrial stromal cells. Trichostatin A and ADC treatment also
      suppressed the cell cycle progression in ectopic endometrial stromal cells. Thus,
      this study provides the first piece of evidence that adenomyosis has epigenetic
      aberration and may also be an epigenetic disease amenable to rectification by
      pharmacological means. This perspective may shed new light onto the pathogenesis
      of adenomyosis and lead to novel ways to treat the disease.

PMID- 20697143
TI  - [The characteristics of blast traumatic brain injury].
AB  - With the increase in terrorist activity in recent times, the number of blast
      injuries has also increased in civilian and military settings. In a recent war,
      the number of patients who suffered blast traumatic brain injury (bTBI)
      increased, so treatment of bTBI is currently a very important issue. Blast injury
      is complicated and can be divided into 4 categories: primary, secondary,
      tertiary, and quaternary. Primary blast injury results from exposure to blast
      waves; secondary blast injury is trauma caused by fragments of explosive devices;
      tertiary blast injury is the result of collision with objects; and quaternary
      blast injury is the result of exposure to toxic and other substances. Blast waves
      mainly injure air-containing organs such as the lung, bowel, and ear. The brain
      may also be affected by blast waves. From the clinical perspective, hyperemia and
      severe cerebral edema occur frequently in patients who sustain significant bTBI.
      Penetrating or closed head injury caused by the explosion may be associated with
      vasospasm and pseudoaneurysm formation. Mild traumatic brain injury during war
      can be associated with posttraumatic stress disorder. To elucidate the mechanism
      of bTBI, many research works using animal models and computer analysis are
      underway. Such studies have so far shown that blast waves can cause damage to the
      brain tissue and cognitive deficits; however, detailed investigations on this
      topic are still required. Treatment of bTBI patients may require clinical
      knowledge and skills related to intensive care, neurology, and neurosurgery.
      Moreover, further research is required in this field.

PMID- 20697144
TI  - [Surgical anatomy for orbitozygomatic approach].

PMID- 20697145
TI  - [Can cerebral blood flow measurement predict clinical outcome in the acute phase
      in patients with artherosclerotic occlusive carotid artery disease?].
AB  - It has been thought that the clinical course of patients with acute carotid
      occlusive disease depends on their collateral cerebral blood flow (CBF) and
      duration of ischemia. However, there have been few clinical reports to prove this
      hypothesis. Therefore, we performed CBF study in patients with artherosclerotic
      carotid occlusive disease in the very acute phase, and precisely assessed the
      prognosis of those patients under intensive medical therapy. This prospective
      study included a total of 44 patients (72+/-13 years) who were admitted to our
      hospital between April, 2007 and December, 2008. To evaluate their initial CBF,
      single photon emission computed tomography (SPECT) studies were performed within
      6 hours after the onset. All patients included in this study were medically
      treated and were periodically followed up by neurological and radiological
      examination. Moreover, in patients with reduced CBF (ipsilateral
      CBF/contralateral CBF x 100: %CBF< 80%), dobutamine-induce hyperdynamic therapy
      was performed. Multivariate analysis was performed to detect significant
      predictors for the occurrence of further cerebral infarction. Multivariate
      analysis showed that the occurrence of further infarction was associated with
      older age and smaller %CBF. Of 44 patients, 21 experienced further cerebral
      infarction within 10 days after onset. Fourteen out of 15 patients with %CBF< 60%
      developed cerebral infarction. This study showed that the prognosis of the
      patients with artherosclerotic carotid occlusive disease in the acute phase is
      associated with their initial residual CBFs. It may be difficult to stop the
      developed cerebral infarction in those patients with %CBF< 60% despite intensive
      medical therapy.

PMID- 20697146
TI  - [Effect of magnetic fields from home-use magnetic induction therapy apparatuses
      on adjustable cerebrospinal fluid shunt valves].
AB  - OBJECTIVE: Cerebrospinal fluid (CSF) shunts are frequently used to treat
      hydrocephalus. The use of a programmable valve allows the operator to easily
      change the opening pressure. In Japan, many people use magnetic induction therapy
      apparatuses in their homes. However, exposing patients with adjustable CSF shunt
      valves to the permanent magnets included in these apparatuses may alter the shunt
      valve's programmed settings or permanently damage the device. Therefore, the goal
      of this study was to determine the health risk associated with magnetic induction
      therapy for patients using programmable CSF shunt valves. METHODS: Five models of
      shunt valves from five different manufacturers, the Miethke proGAV (proGAV), the
      Codman Hakim programmable valve (CHPV), Sophysa Sophy model SM8 (Sophy valve),
      Sophysa Polaris model SPV (Polaris valve), and Strata II valve (Strata valve)
      were evaluated in this study. Magnetic field interactions were determined for the
      programmable valves by using magnetic stones with various magnetic flux
      densities. The maximum distance between the valve and the magnetic stone
      affecting the valve pressure setting was measured by X-ray. RESULTS: The proGAV
      and Polaris valve were immune to unintentional reprogramming by the magnetic
      stones. The CHPV, Sophy valve and Strata valve, however, randomly changed
      settings by magnetic stones. CONCLUSIONS: Whereas the CHPV, Sophy valve and
      Strata valve were promptly reset by exposure to a magnetic stone with a similar
      strength to that used in magnetic induction therapy, proGAV and Polaris valve
      were resistant to inadvertent reprogramming when exposed to magnets up to 190 mT.

PMID- 20697147
TI  - [Two cases of cervical carotid artery stenosis with high risk post-operative
      hyperperfusion treated with dexmedetomidine after carotid endarterectomy].
AB  - Dexmedetomidine is a central alpha2 adrenoceptor agonist recently shown to be a
      safe and acceptable sedative agent for patients requiring sedation after brain
      surgery. We report two patients successfully treated by carotid endarterectomy
      (CEA) with postoperative management under dexmedetomidine anesthesia for
      transient ischemic attack (TIA) resulting from severe stenosis of the internal
      carotid artery (ICA). Case 1: A 75-year-old man was admitted to our hospital with
      aphasia and weakness of the right side of his body. Although no evidence of acute
      cerebral infarction was obtained on magnetic resonance imaging (MRI)/diffusion
      weighted image (DWI), MR angiography (MRA) revealed severe stenosis of the left
      cervical ICA. (123)I-IMP-single photon emission tomography (SPECT) and
      transcranial Doppler (TCD) revealed marked reduction of cerebral blood flow in
      the left cerebral hemisphere. Although CEA induced hyperperfusion, aggressive
      control of blood pressure under dexmedetomidine anesthesia enabled effective
      management of the resulting hyperperfusion syndrome. The patient was discharged
      without neurological deficits. Case 2: A 68-year-old man was admitted to our
      hospital with amaurosis fugax and numbness of the right side of his body.
      Although no evidence of acute cerebral infarction was obtained on MRI/DWI, MRA
      disclosed severe stenosis of the left cervical ICA. (123)I-IMP-SPECT revealed
      extremely low perfusion and disturbance of vascular reactivity in the territory
      of the left ICA. Although conservative therapy was performed, crescendo TIA was
      noted. Revascularization using CEA was therefore performed. After surgery,
      hyperperfusion was observed in the same fashion as in case 1, and again
      aggressive control of blood pressure under dexmedetomidine anesthesia enabled
      effective management of the resulting hyperperfusion syndrome. The patient was
      discharged 1 month postoperatively without neurological deficits. Dexmedetomidine
      is a safe and acceptable sedative drugs preventing hyperperfusion syndrome after
      CEA.

PMID- 20697148
TI  - [A case of traumatic petrous portion internal carotid artery aneurysm treated by
      endovascular parent artery occlusion].
AB  - Traumatic aneurysms are rare lesions. They differ markedly from saccular
      aneurysms in their clinical presentation and therapy. Early diagnosis of
      traumatic aneurysms is usually difficult. A 52-year-old female presented with
      massive epistaxis and ear bleeding caused by a traffic accident. On admission,
      her consciousness level was 7 points of the Glasgow coma scale. Computed
      tomography revealed hematoma in the sphenoid sinus and fractures in the right
      petrous bone, and right acute subdural hematoma. 7 years after trauma, she
      presented ear bleeding. Cerebral angiography showed a giant traumatic aneurysm at
      the petrous segment of the right internal carotid artery. Test occlusion of the
      right internal carotid artery was performed and was well tolerated without
      development of focal neurological deficits, so the right internal carotid artery
      was occluded using endovascular techniques. We recommend that more attention be
      paid to the traumatic aneurysm of the C4 to C5 portion when patients with skull
      base fracture are diagnosed.

PMID- 20697149
TI  - [Removal of an arteriovenous malformation near the pyramidal tract using the
      neuronavigation system: a case report].
AB  - A 20-year-old female presented with sudden severe headaches. Computed tomography
      showed an intraventricular hemorrhage and slightly dilated lateral ventricles.
      Her neurological examinations revealed no abnormalities. Magnetic resonance (MR)
      images and cerebral angiography revealed arteriovenous malformation (AVM) in the
      right parietal lobe. The size of the nidus was 1.8 cm, and it was located in the
      deep white matter. It was fed by middle cerebral arteries and drained by the vein
      of Galen. Diffusion tensor tractography (DTT) demonstrated that the right
      pyramidal tract was situated close to the nidus. The AVM was surgically resected
      completely, without any complications, using intraoperative neuronavigation image
      guidance. Neuronavigation images combined with DTT are useful for surgical
      resection of AVM that is located close to the pyramidal tract.

PMID- 20697150
TI  - [Cyst formation after radiosurgery for brain arteriovenous malformation treated
      with cystoperitoneal shunt].
AB  - Gamma knife and CyberKnife radiosurgery are well established and less invasive
      treatments for arteriovenous malformation. Delayed cyst formation is a rare but
      well-known complication of radiosurgery for arteriovenous malformations. The
      optimal treatment of cysts forming after radiosurgery remains debatable. We
      present a case of cyst formation after radiosurgery for brain arteriovenous
      malformation that was treated with a cystoperitoneal shunt (C-P shunt). A 36-year
      old woman presented with left hemiparesis and numbness. Computed tomography (CT)
      revealed intracranial hemorrhage in the right basal ganglia. Digital subtraction
      angiography revealed arteriovenous malformation in the brain. Intravascular
      embolization was performed three times and radiosurgery was performed twice,
      whereby complete obliteration of the nidus was achieved. Six and a half years
      later, routine follow-up magnetic resonance imaging revealed cyst formation, and
      the patient gradually developed left hemiparesis. First, we performed
      stereotactic cyst aspiration. This initially resulted in a reduction in the size
      of the cyst and disappearance of left hemiparesis, but within a short time, the
      cyst increased in size again and there was recurrence of hemiparesis. Therefore,
      an Ommaya reservoir was established; aspiration of the cyst through this
      reservoir brought about an initial reduction in cyst size and alleviation of
      symptoms; however, no further reduction in cyst size or improvement in symptoms
      could be achieved. Twenty months after the placement of the Ommaya reservoir, we
      performed a C-P shunt operation. After the operation, further reduction in the
      cyst size and complete symptomatic recovery were observed.

PMID- 20697151
TI  - [A case of dural arteriovenous fistula associated with subcortical and subdural
      hemorrhage].
AB  - We encountered a case of dural arteriovenous fistula (AVF) in which a cortical
      venous drainage was successfully treated by direct surgery. A 68-year-old man
      complained of headache and visual disturbance. CT on admission revealed
      intracerebral hematoma in the left occipital lobe and subdural hemorrhage in the
      left temporooccipital region. Angiography showed dural AVF in the left occipital
      region, which was type IV classified by Cognard and a varix of the draining vein.
      We performed direct surgery to remove the hematoma and obliteration of the
      draining vein was observed 10 days after onset. Intraoperative angiography via
      the middle meningeal artery which fed the dural AVF was very useful in the
      identification of the dural AVF and the varix and also to certify the
      obliteration of the fistula. Postoperative angiography showed disappearance of
      dural AVF. The patient had a good clinical course. Early direct surgery in this
      type of dural AVF is necessary in order to prevent another hemorrhage from the
      varix.

PMID- 20697152
TI  - [Understanding clinical neuropsychology: a basic approach (3) cognitive
      dysfunction in toxic disorders].

PMID- 20697155
TI  - Myeloid mineralocorticoid receptor controls macrophage polarization and
      cardiovascular hypertrophy and remodeling in mice.
AB  - Inappropriate excess of the steroid hormone aldosterone, which is a
      mineralocorticoid receptor (MR) agonist, is associated with increased
      inflammation and risk of cardiovascular disease. MR antagonists are
      cardioprotective and antiinflammatory in vivo, and evidence suggests that they
      mediate these effects in part by aldosterone-independent mechanisms. Here we have
      shown that MR on myeloid cells is necessary for efficient classical macrophage
      activation by proinflammatory cytokines. Macrophages from mice lacking MR in
      myeloid cells (referred to herein as MyMRKO mice) exhibited a transcription
      profile of alternative activation. In vitro, MR deficiency synergized with
      inducers of alternatively activated macrophages (for example, IL-4 and agonists
      of PPARgamma and the glucocorticoid receptor) to enhance alternative activation.
      In vivo, MR deficiency in macrophages mimicked the effects of MR antagonists and
      protected against cardiac hypertrophy, fibrosis, and vascular damage caused by L
      NAME/Ang II. Increased blood pressure and heart rates and decreased circadian
      variation were observed during treatment of MyMRKO mice with L-NAME/Ang II. We
      conclude that myeloid MR is an important control point in macrophage polarization
      and that the function of MR on myeloid cells likely represents a conserved
      ancestral MR function that is integrated in a transcriptional network with
      PPARgamma and glucocorticoid receptor. Furthermore, myeloid MR is critical for
      blood pressure control and for hypertrophic and fibrotic responses in the mouse
      heart and aorta.

PMID- 20697156
TI  - Prkar1a is an osteosarcoma tumor suppressor that defines a molecular subclass in
      mice.
AB  - Some cancers have been stratified into subclasses based on their unique
      involvement of specific signaling pathways. The mapping of human cancer genomes
      is revealing a vast number of somatic alterations; however, the identification of
      clinically relevant molecular tumor subclasses and their respective driver genes
      presents challenges. This information is key to developing more targeted and
      personalized cancer therapies. Here, we generate a new mouse model of genomically
      unstable osteosarcoma (OSA) that phenocopies the human disease. Integrative
      oncogenomics pinpointed cAMP-dependent protein kinase type I, alpha regulatory
      subunit (Prkar1a) gene deletions at 11qE1 as a recurrent genetic trait for a
      molecularly distinct subclass of mouse OSA featuring RANKL overexpression. Using
      mouse genetics, we established that Prkar1a is a bone tumor suppressor gene
      capable of directing subclass development and driving RANKL overexpression during
      OSA tumorigenesis. Finally, we uncovered evidence for a PRKAR1A-low subset of
      human OSA with distinct clinical behavior. Thus, tumor subclasses develop in mice
      and can potentially provide information toward the molecular stratification of
      human cancers.

PMID- 20697157
TI  - Argonaute proteins are key determinants of RNAi efficacy, toxicity, and
      persistence in the adult mouse liver.
AB  - shRNA overexpression from viral gene therapy vectors can trigger cytotoxicity
      leading to organ failure and lethality in mice and rats. This process likely
      involves saturation of endogenous cellular RNAi factors including exportin-5 (Xpo
      5). Here, we have shown that Xpo-5 overexpression enhanced shRNA efficiency in
      the liver of adult mice but increased hepatotoxicity. We identified the 4 members
      of the human Argonaute (Ago) protein family as downstream factors involved in
      saturation of endogenous cellular RNAi, all of which were able to interact with
      shRNAs in cells and mice. In Ago/shRNA coexpression studies, Ago-2 (Slicer) was
      the primary rate-limiting determinant of both in vitro and in vivo RNAi efficacy,
      toxicity, and persistence. In adult mice, vector-based Ago-2/Xpo-5 coexpression
      enhanced U6-driven shRNA silencing of exogenous and endogenous hepatic targets,
      reduced hepatotoxicity, and extended RNAi stability by more than 3 months. Use of
      weaker RNA polymerase III promoters to minimize shRNA expression likewise
      alleviated in vivo toxicity and permitted greater than 95% persistent knockdown
      of hepatitis B virus and other transgenes in mouse liver for more than 1 year.
      Our studies substantiate that abundant small RNAs can overload the endogenous
      RNAi pathway and reveal possible strategies for reducing hepatotoxicity of short-
      and long-term clinical gene silencing in humans.

PMID- 20697160
TI  - Hair tourniquet syndrome.
AB  - The hair tourniquet syndrome is a rare disorder. This syndrome has been described
      as involving the fingers, the toes and even the genitals. We report a case of
      hair tourniquet syndrome affecting multiple toes of an infant. After the hair
      fiber was removed there was a fast healing period and no signs of tissue necrosis
      were seen. The prompt diagnosis and treatment of the condition is vital to attain
      a good outcome and prevent further harm to the child.

PMID- 20697159
TI  - CD13 is a therapeutic target in human liver cancer stem cells.
AB  - Cancer stem cells (CSCs) are generally dormant or slowly cycling tumor cells that
      have the ability to reconstitute tumors. They are thought to be involved in tumor
      resistance to chemo/radiation therapy and tumor relapse and progression. However,
      neither their existence nor their identity within many cancers has been well
      defined. Here, we have demonstrated that CD13 is a marker for semiquiescent CSCs
      in human liver cancer cell lines and clinical samples and that targeting these
      cells might provide a way to treat this disease. CD13+ cells predominated in the
      G0 phase of the cell cycle and typically formed cellular clusters in cancer foci.
      Following treatment, these cells survived and were enriched along the fibrous
      capsule where liver cancers usually relapse. Mechanistically, CD13 reduced ROS
      induced DNA damage after genotoxic chemo/radiation stress and protected cells
      from apoptosis. In mouse xenograft models, combination of a CD13 inhibitor and
      the genotoxic chemotherapeutic fluorouracil (5-FU) drastically reduced tumor
      volume compared with either agent alone. 5-FU inhibited CD90+ proliferating CSCs,
      some of which produce CD13+ semiquiescent CSCs, while CD13 inhibition suppressed
      the self-renewing and tumor-initiating ability of dormant CSCs. Therefore,
      combining a CD13 inhibitor with a ROS-inducing chemo/radiation therapy may
      improve the treatment of liver cancer.

PMID- 20697158
TI  - Phosphorylation of IRF4 by ROCK2 regulates IL-17 and IL-21 production and the
      development of autoimmunity in mice.
AB  - Deregulated production of IL-17 and IL-21 plays a key pathogenic role in many
      autoimmune disorders. A delineation of the mechanisms that underlie the
      inappropriate synthesis of IL-17 and IL-21 in autoimmune diseases can thus
      provide important insights into potential therapies for these disorders. Here we
      have shown that the serine-threonine kinase Rho-associated, coiled-coil
      containing protein kinase 2 (ROCK2) becomes activated in mouse T cells under Th17
      skewing conditions and phosphorylates interferon regulatory factor 4 (IRF4), a
      transcription factor that is absolutely required for the production of IL-17 and
      IL-21. We furthermore demonstrated that ROCK2-mediated phosphorylation of IRF4
      regulated the synthesis of IL-17 and IL-21 and the differentiation of Th17 cells.
      Whereas CD4+ T cells from WT mice activated ROCK2 physiologically under Th17
      conditions, CD4+ T cells from 2 different mouse models of spontaneous
      autoimmunity aberrantly activated ROCK2 under neutral conditions. Moreover,
      administration of ROCK inhibitors ameliorated the deregulated production of IL-17
      and IL-21 and the inflammatory and autoantibody responses observed in these
      autoimmune mice. Our findings thus uncover a crucial link among ROCK2, IRF4, and
      the production of IL-17 and IL-21 and support the idea that selective inhibition
      of ROCK2 could represent an important therapeutic regimen for the treatment of
      autoimmune disorders.

PMID- 20697161
TI  - Evolution of tigecycline resistance in Klebsiella pneumoniae in a single patient.
AB  - Carbapenemase-producing Klebsiella pneumoniae infections carry serious clinical
      and infection-control implications. Isolates possessing such hydrolyzing enzymes
      have been described in the United States and around the world. Besides being
      resistant to carbapenems, they usually confer resistance to fluoroquinolones,
      piperacillin-tazobactam, and extended-spectrum cephalosporins. Tigecycline
      demonstrates in vitro activity against these organisms, but reported resistance
      raises concern about tigecycline use for these infections. We describe a
      carbapenemase-producing K pneumoniae evolving resistance to tigecycline in a 75
      year-old male after a prolonged stay in a critical care unit.

PMID- 20697162
TI  - Diagnosis of endocarditis caused by Mycobacterium abscessus.
AB  - We report a fatal case of native valve endocarditis due to Mycobacterium
      abscessus in a hemodialysis patient. The diagnosis was based on culture isolation
      of acid-fast bacilli from peripheral blood and a permanent catheter tip, and
      their identification as M abscessus by a reverse hybridization-based assay and
      direct DNA sequencing of the 16S-23S internal transcribed spacer region. Rapid
      diagnosis and combination therapy are essential to minimize mortality due to this
      pathogen. Although combination therapy was started with clarithromycin and
      tigecycline, the patient refused to take clarithromycin due to severe abdominal
      pain. The patient became afebrile after therapy with tigecycline alone although
      bacteremia persisted. He was discharged against medical advice and readmitted
      three months later for persistent fever. His blood cultures again yielded M
      abscessus and a transesophageal echocardiogram showed two mobile vegetations. The
      patient was noncompliant with therapy and died due to cardiac arrest and
      multiorgan failure. This report shows that M abscessus should also be considered
      in the differential diagnosis of infective endocarditis in hemodialysis patients.

PMID- 20697163
TI  - A hepatitis C-positive patient with new onset of nephrotic syndrome and systemic
      amyloidosis secondary to common variable immunodeficiency.
AB  - Common variable immunodeficiency (CVID) is a heterogenous group of predominantly
      antibody-deficiency disorders that make up the greatest proportion of patients
      with symptomatic primary hypogammaglobulinemia. The rare coincidence of
      amyloidosis and hypogammaglobulinemia has been reported previously. Contrary to
      the usual insidious, slowly progressive disease following hepatitis C infection,
      a rapidly progressive cirrhotic form can develop in hypogammaglobulinemic
      patients. We report a HCV-positive patient with a new onset of nephrotic syndrome
      and systemic amyloidosis secondary to CVID. Blood analyses showed serum
      creatinine of 1.8 mg/dL and serum albumin of 3.1 gm/dL; 24-h urinary protein was
      11 800 mg/day. Serum immunoglobulin levels were IgG 340 mg/dL, IgM 18 mg/dL, IgA
      11 mg/dL. Duodenal biopsy revealed AA-type amyloidosis with potassium
      permanganate and Congo red staining. After a month of antiproteinuric therapy,
      the proteinuria was reduced to 3350 mg/day.

PMID- 20697164
TI  - A rare case of seronegative neurobrucellosis.
AB  - Neurobrucellosis is one of the complications of brucellosis. We report a rare
      case of a 17-year-old girl with seronegative neurobrucellosis and depression and
      diplopia. Results of agglutination tests for Brucella both in serum and CSF were
      negative. Diagnosis was made only by positive culture of Brucella mellitensis
      with inoculation of the patient's cerebrospinal fluid in a BACTEC 9050 System.
      The patient was successfully treated using ceftriaxone, doxycycline and
      rifampicin therapy for six months.

PMID- 20697165
TI  - Validity and reliability of the European Organization for Research and Treatment
      in Cancer Quality of Life Questionnaire (EORTC QLQ): experience from Kuwait using
      a sample of women with breast cancer.
AB  - BACKGROUND AND OBJECTIVES: Although the EORTC QLQ-C30 and its breast-specific
      module (BR-23) are widely used instruments, the few reports on their psychometric
      characteristics from Arab and neighboring countries involved limited analyses.
      Our objective was to assess the psychometric characteristics of both
      questionnaires using the responses of a larger sample of Arab women. METHODS:
      Participants were consecutive clinic attendees at the Kuwait Cancer Control
      Center. The indices assessed were alpha coefficients, item-internal consistency
      (IIC), item-discriminant validity (IDV), and known-groups validity. RESULTS: The
      348 women were aged 48.3 (10.3) years. The intra-class correlation for the test
      retest statistic and the internal consistency values for the multi-item scales
      were >0.7 alpha. With the exception of the pain subscale, all items met the IIC
      criterion of >0.4 correlation with the corresponding scale. For IDV, the BR-23
      performed better than the QLQ-C30. The scale scores discriminated between
      patients at different disease stages, and between sick and well populations.
      CONCLUSION: With the exception of the pain subscale, the Arabic version of the
      questionnaires is psychometrically sound.

PMID- 20697166
TI  - Assessment of the accreditation standards of the Central Board for Accreditation
      of Healthcare Institutions in Saudi Arabia against the principles of the
      International Society for Quality in Health Care (ISQua).
AB  - BACKGROUND AND OBJECTIVES: Accreditation is usually a voluntary program, in which
      trained external peer reviewers evaluate health care organization's compliance
      with pre-established performance standards. Interest in accreditation is growing
      in developing countries, but there is little published information on the
      challenges faced by new programs. In Saudi Arabia, the Central Board for
      Accreditation of Healthcare Institutions (CBAHI) was established to formulate and
      implement quality standards in all health sectors across the country. The
      objective of this study was to assess a developing accreditation program (CBAHI
      standards) against the International Society for Quality in Health Care (ISQua)
      principles to identify opportunities for improvement of the CBAHI standards.
      METHODS: A qualitative appraisal and assessment of CBAHI standards was conducted
      using the published ISQua principles for accreditation standards. RESULTS: The
      CBAHI standards did not describe the process of development, evaluation or
      revision of the standards. Several standards are repetitive and ambiguous. CBAHI
      standards lack measurable elements for each standard. CBAHI standards met only
      one criterion (11.1%) of the Quality Improvement principle, two criteria (22.2%)
      of Patient/Service User Focus principle, four criteria (40%) of the
      Organizational Planning and Performance principle, the majority (70%) of the
      criteria for the safety principle, only one criteria (7.1%) for the Standards
      Development principle, and two criteria (50%) of the Standards Measurement
      principle. CONCLUSIONS: CBAHI standards need significant modifications to meet
      ISQua principles. New and developing accreditation programs should be encouraged
      to publish and share their experience in order to promote learning and
      improvement of local accreditation programs worldwide.

PMID- 20697168
TI  - Diagnosis: Kartagener syndrome.

PMID- 20697167
TI  - A middle-aged woman with cough, expectoration and fever.

PMID- 20697169
TI  - Terbutaline versus salbutamol for suppression of preterm labor: a randomized
      clinical trial.
AB  - BACKGROUND AND OBJECTIVE: Preterm labor (PTL) is a common medical problem during
      pregnancies and is associated with neonatal mortality and morbidity. Beta
      adrenergic agonists are among the most commonly used tocolytic agents. The aim of
      this study was to compare the effectiveness, safety and adverse effects of
      terbutaline with those of salbutamol in the prolongation of pregnancy beyond 48
      hours and until 37 weeks of gestation. PATIENTS AND METHODS: Two hundred women
      with PTL were randomly assigned to receive subcutaneous terbutaline (250 MUg) or
      intravenous salbutamol (0.1 mg) followed by oral terbutaline (20 mg/d) or oral
      salbutamol (24 mg/d) as maintenance. The efficacy, side effects and complications
      after 48 hours and until 37 weeks of gestation were analyzed and compared.
      RESULTS: There was no significant difference between the two groups in success
      rate within 48 hours (P= .091). Gestational age at delivery (P=.031) and the
      number of days for which the gestation was prolonged (P=.024) were significantly
      higher in those receiving terbutaline. Adverse effects, including tachycardia
      (P=.007) and anxiety (P=.006), were experienced more in the salbutamol group.
      Birth weight was significantly lower in the salbutamol group (P=.001).
      CONCLUSION: Terbutaline provided more effective tocolysis with fewer adverse
      effects and a better neonatal outcome. However, terbutaline and salbutamol are
      equally effective in the first 48 hours.

PMID- 20697170
TI  - The first national public breast cancer screening program in Saudi Arabia.
AB  - BACKGROUND AND OBJECTIVES: Despite its relatively low incidence in Saudi Arabia,
      breast cancer has been the most common cancer among Saudi females for the past 12
      consecutive years. The objective of this study was to report the results of the
      first national public breast cancer screening program in Saudi Arabia. METHODS:
      Women 40 years of age or older underwent breast cancer screening. Mammograms were
      scored using the Breast Imaging-Reporting and Data System (BI-RADS). Correlations
      between imaging findings, risk factors and pathological findings were analyzed.
      RESULTS: Between September 2007 and April 2008, 1215 women were enrolled. The
      median age was 45 years, and median body mass index was 31.6 kg/m 2 . Sixteen
      cases of cancer were diagnosed. No cancer was diagnosed in 942 women with R1/R2
      scores, and only 1 case of cancer was diagnosed in 228 women with R0/R3 scores.
      However, among 26 women with R4/R5 scores, 50% had malignant disease and 35% had
      benign lesions. No correlation was found between known risk factors and imaging
      score or cancer diagnosis. CONCLUSIONS: Public acceptance of the breast cancer
      screening program was encouraging. Longitudinal follow-up will help in better
      determining the risk factors relevant to our patient population.

PMID- 20697171
TI  - Methicillin-resistant Staphylococcus aureus nosocomial infection trends in
      Hospital Universiti Sains Malaysia during 2002-2007.
AB  - BACKGROUND AND OBJECTIVES: Methicillin-resistant Staphylococcus aureus (MRSA) is
      a major nosocomial pathogen that causes severe morbidity and mortality in many
      hospitals worldwide. The aim of the present study was to assess the burden of
      MRSA nosocomial infection, its association with factors of interest, and its
      antimicrobial susceptibility. METHODS: This was a retrospective analysis of a
      database of all S aureus that were cultured from patients admitted to the
      different wards of Hospital Universiti Sains Malaysia (HUSM) over a period of 6
      years. RESULTS: The MRSA infections rate was 10.0 per 1000 hospital admissions.
      The incidence density rate of MRSA infections during the study period was 1.8 per
      1000 patient-days, with annual rates ranging from 0.95 to 3.47 per 1000 patient
      days. Duration of hospitalization, previous antibiotic use, and bedside invasive
      procedures were significantly higher among MRSA than methicillin-sensitive S
      aureus patients (P>.05). The highest number of MRSA infections were found in
      orthopedic wards (25.3%), followed by surgical wards (18.2%) and intensive care
      units (ICUs) (16.4%). All MRSA isolates were resistant to erythromycin (98.0%),
      co-trimoxazole (94.0%) and gentamicin (92.0%). Clindamycin was the best
      antibiotic with only 6% resistance. All MRSA isolates were sensitive to
      vancomycin. CONCLUSION: The rate of nosocomial MRSA infection per 1000 admissions
      was higher than that in other studies. The three factors associated most
      significantly with acquired MRSA infections included duration of hospitalization,
      antibiotic use, and bedside invasive procedures. This study confirmed that
      vancomycin-resistant S aureus has not yet been established in HUSM.

PMID- 20697172
TI  - Prevalence of malnutrition in Saudi children: a community-based study.
AB  - BACKGROUND AND OBJECTIVE: There is no published information on the prevalence of
      malnutrition in Saudi Arabia. The objective of this study was to establish the
      prevalence data. METHODS: The prevalence of nutritional indicators in the form of
      underweight, stunting, and wasting in a national sample of children younger than
      5 years of age was calculated using the new WHO standards as reference.
      Calculations were performed using the corresponding WHO software. The prevalence
      of moderate and severe underweight, wasting and stunting, was defined as the
      proportion of children whose weight for age, weight for height, and height for
      age were below -2 and -3 standard deviation scores, respectively. RESULTS: The
      number of children younger than 5 years of age was 15 516 and 50.5% were boys.
      The prevalence of moderate and severe underweight was 6.9% and 1.3%,
      respectively. The prevalence of moderate and severe wasting was 9.8% and 2.9%,
      respectively. Finally, the prevalence of moderate and severe stunting was 10.9%
      and 2.8%, respectively. The prevalence was lower in girls for all indicators.
      Comparison of the prevalence of nutritional indicators in selected countries
      demonstrates large disparity with an intermediate position for Saudi Arabia.
      CONCLUSION: This report establishes the national prevalence of malnutrition among
      Saudi children. Compared to data from other countries, these prevalence rates are
      still higher than other countries with less economic resources, indicating that
      more efforts are needed to improve the nutritional status of children.

PMID- 20697173
TI  - Body mass index and obstetric outcomes in pregnant in Saudi Arabia: a prospective
      cohort study.
AB  - BACKGROUND AND OBJECTIVES: We examined the effect of body mass index in early
      pregnancy on pregnancy outcome since no study in Saudi Arabia has addressed this
      question. METHODS: This prospective cohort study involved women registered for
      antenatal care during the first month of pregnancy at primary health care centers
      in Al-Hassa, Saudi Arabia. Data was collected from records and by direct
      interview. RESULTS: The study included 787 women. Compared to normal weight women
      (n=307), overweight (n=187) and obese (n=226) women were at increased risk for
      pregnancy-induced hypertension (RR=4.9 [95% CI 1.6-11.1] and 6.1 [95% CI 2.1
      17.8], respectively), gestational diabetes (RR=4.4 [95% CI 1.2-16.3] and 8.6 [95%
      CI 2.6-28.8]), preeclamptic toxemia (RR=3.8 [95% CI 1.1-14.6] and 5.9 [95% CI 1.7
      20.4]), urinary tract infections (RR=1.4 [95% CI 0.5-3.9] and 3.7 [95% CI 1.7
      6.2]), and cesarean delivery (RR=2.0 [95% CI 1.3-3.0] in obese women). Neonates
      born to obese women had an increased risk for postdate pregnancy (RR=3.7 [95% CI
      1.2-11.6]), macrosomia (RR=6.8 [95% CI 1.5-30.7]), low 1-minute Apgar score
      (RR=1.9 [95% CI 1.1-3.6]), and admission to neonatal care units (RR=2.1 [95% CI
      1.2-2.7]). On the other hand, low birth weight was less frequent among obese
      women (RR=0.5 [95% CI 0.3-0.9]) while the risk was high among underweight women
      (RR=2.3 [95% CI 1.4-3.8]). CONCLUSION: Even with adequate prenatal care,
      overweight and obesity can adversely affect pregnancy outcomes.

PMID- 20697174
TI  - Prevalence of antimicrobial resistance among gram-negative isolates in an adult
      intensive care unit at a tertiary care center in Saudi Arabia.
AB  - BACKGROUND AND OBJECTIVES: Patients in the ICU have encountered an increasing
      emergence and spread of antibiotic-resistant pathogens. We examined patterns of
      antimicrobial susceptibility in gram-negative isolates to commonly used drugs in
      an adult ICU at a tertiary care hospital in Riyadh, Saudi Arabia. METHODS: A
      retrospective study was carried out of gram-negative isolates from the adult ICU
      of King Fahad National Guard Hospital (KFNGH) between 2004 and 2009. Organisms
      were identified and tested by an automated identification and susceptibility
      system, and the antibiotic susceptibility testing was confirmed by the disk
      diffusion method. RESULTS: The most frequently isolated organism was
      Acinetobacter baumannii, followed by Pseudomonas aeruginosa, Escherichia coli,
      Klebsiella pnemoniae, Stenotrophomonas maltophilia, and Enterobacter. Antibiotic
      susceptibility patterns significantly declined in many organisms, especially A
      baumannii, E coli, S marcescens, and Enterobacter. A baumannii susceptibility was
      significantly decreased to imipenem (55% to 10%), meropenem (33% to 10%),
      ciprofloxacin (22% to 10%), and amikacin (12% to 6%). E coli susceptibility was
      markedly decreased (from 75% to 50% or less) to cefuroxime, ceftazidime,
      cefotaxime, and cefepime. S marcescens susceptibility was markedly decreased to
      cefotaxime (100% to 32%), ceftazidime (100% to 35%), and cefepime (100% to 66%).
      Enterobacter susceptibility was markedly decreased to ceftazidime (34% to 5%),
      cefotaxime (34% to 6%), and pipracillin-tazobactam (51% to 35%). Respiratory
      samples were the most frequently indicative of multidrug-resistant pathogens
      (63%), followed by urinary samples (57%). CONCLUSION: Antimicrobial resistance is
      an emerging problem in the KFNGH ICU, justifying new more stringent antibiotic
      prescription guidelines. Continuous monitoring of antimicrobial susceptibility
      and strict adherence to infection prevention guidelines are essential to
      eliminate major outbreaks in the future.

PMID- 20697176
TI  - Drug-eluting stents vs bypass surgery for unprotected left main disease.

PMID- 20697177
TI  - A national survey on myocarditis associated with the 2009 influenza A (H1N1)
      pandemic in Japan.
AB  - BACKGROUND: An influenza pandemic occurred in 2009 and myocarditis associated
      with the 2009 influenza A (H1N1) pandemic was reported among hospitalized
      patients from August 2009. METHODS AND RESULTS: The Japanese Circulation Society
      organized the Clinical Research Committee on Myocarditis Associated with
      Influenza Pandemic A (H1N1) 2009 and called for a case report on myocarditis for
      a national survey. The diagnosis of myocarditis was performed using the
      Guidelines for the Diagnosis and Treatment of Myocarditis (JCS 2009). Fifteen
      patients were reported to the committee. Fulminant myocarditis developed in 10
      patients. Mechanical circulatory support (intra-aortic balloon pumping (IABP)
      and/or percutaneous cardiopulmonary support (PCPS)) was used on all 10 patients,
      8 of whom were rescued. Abnormalities on echocardiography and elevated cardiac
      enzymes were seen in most of the patients. Myocarditis was found by
      endomyocardial biopsy in 6 patients. Three patients had complications with
      pneumonia. CONCLUSIONS: In reality, myocarditis associated with pandemic
      influenza A (H1N1) seemed to be more common in hospitalized patients, compared
      with previous seasonal influenza virus outbreaks. To avoid misdiagnosis of acute
      myocarditis associated with influenza pandemic A (H1N1) 2009, it is essential to
      determine the characteristic symptoms, signs, and laboratory findings of acute
      myocarditis during influenza pandemics. Mechanical circulatory support (IABP
      and/or PCPS) was required to rescue patients with fulminant myocarditis.

PMID- 20697178
TI  - Reduction of the PaO2/FiO2 ratio in acute aortic dissection - relationship
      between the extent of dissection and inflammation -.
AB  - BACKGROUND: Acute aortic dissection (AAD) often accompanies acute respiratory
      failure. The aim of this study was to clarify the relationship between the
      incidence of oxygenation impairment and the extent of distal type AAD. METHODS
      AND RESULTS: A total of 49 patients with medically treated distal type AAD were
      retrospectively examined. AAD% was defined as the percentage of the volume of
      false lumen to that of aorta in the descending aorta. AAD% was measured by
      computed tomography. C-reactive protein (CRP) levels, white blood cell (WBC)
      counts, body temperature and arterial partial pressure of oxygen/fraction of
      inspired oxygen (PaO(2)/FiO(2)) ratio were measured serially. Oxygenation
      impairment was defined as a PaO(2)/FiO(2) ratio <= 200. This occurred in 19
      patients (39%). In patients with oxygenation impairment, AAD% (50.8 +/- 10.9% vs
      28.0 +/- 11.9%, P<0.001), peak CRP levels (15.2 +/- 6.5 mg/dl vs 9.6 +/- 4.6
      mg/dl, P<0.001), peak WBC counts (13,600 +/- 3,700/ul vs 10,400 +/- 2,800 /ul,
      P=0.001) and body temperature (38.1 +/- 0.5 degrees C vs 37.8 +/- 0.4 degrees C,
      P=0.045) were higher than those without oxygenation impairment. It was found that
      there were inverse correlations between the PaO(2)/FiO(2) ratio and AAD% (r=
      0.604, P<0.001), and between peak CRP levels and the PaO(2)/FiO(2) ratio (r=
      0.635, P<0.001). Multivariate analysis demonstrated that the only independent
      predictor of oxygenation impairment was AAD% (odds ratio, 1.323; 95% confidence
      interval, 1.035-1.691, P=0.026). CONCLUSIONS: Respiratory failure in AAD appears
      to be closely correlated with the amount of aortic injury, possibly mediated by
      the magnitude of the systemic inflammatory reaction to the aortic injury.

PMID- 20697179
TI  - Automated assessment of myocardial viability after acute myocardial infarction by
      global longitudinal peak strain on low-dose dobutamine stress echocardiography.
AB  - BACKGROUND: Low-dose dobutamine stress echocardiography (DSE) assesses myocardial
      viability at the early stage of acute myocardial infarction (AMI), but its
      assessment is subjective and variable. Automated function image (AFI) determines
      global longitudinal peak strain (GLPS) based on tissue tracking technique. The
      ability of GLPS obtained by AFI during dobutamine stress to assess myocardial
      viability after AMI was investigated. METHODS AND RESULTS: Low-dose DSE at day 3
      in 23 consecutive patients with AMI was performed using Vivid 7 (GE Healthcare).
      Segmental longitudinal peak strain with AFI and obtained GLPS was analyzed. Wall
      motion score index (WMSI) by echocardiography 1 month later was determined. In 18
      patients, left ventriculography was also performed at 3.2+/-1.5 months later to
      obtain left ventricular ejection fraction (LVEF) and regional wall motion (RWM,
      SD/chord). GLPS was improved during dobutamine infusion at 10 ug . kg(-1) . min(
      1) (-12.9 +/- 3.5% to -15.2 +/- 3.6%, P=0.0004). GLPS during dobutamine stress
      showed good correlations with follow-up WMSI (R=0.47, P=0.02), with peak CK-MB (R
      = 0.52, P=0.01), with RWM (R = -0.48, P=0.04), and with LVEF (R = -0.54, P=0.02),
      whereas GLPS at baseline showed no correlations with them. Averaged segmental
      peak strain at baseline and during stress were correlated with follow-up WMSI (R
      = 0.50 and 0.43, respectively), but not with LVEF. CONCLUSIONS: GLPS during
      dobutamine stress determined by AFI is a promising, objective index to assess
      myocardial viability on the early stage of AMI.

PMID- 20697180
TI  - Marked hemodynamic improvements by high-dose epoprostenol therapy in patients
      with idiopathic pulmonary arterial hypertension.
AB  - BACKGROUND: The appropriate dose range of epoprostenol is thought to be 25-40 ng
      . kg(-1) . min(-1) based on the results of previous studies showing that
      epoprostenol therapy reduced mean pulmonary artery pressure (mPAP) by 12-22% and
      pulmonary vascular resistance (PVR) by 32-53% compared with baseline values in
      patients with idiopathic pulmonary arterial hypertension (IPAH). However, the
      efficacy of treatment of IPAH patients with epoprostenol >40 ng . kg(-1) . min(
      1) has not been determined and this was the aim of the present study. METHODS AND
      RESULTS: The study group comprised 16 consecutive patients, none of whom died; 2
      dropped out because they could not be titrated up as needed to the highest
      effective epoprostenol dose. Hemodynamics were evaluated in 14 IPAH patients who
      received high-dose epoprostenol monotherapy. The mean epoprostenol dosage was 107
      +/- 40 ng . kg(-1) . min(-1) (range, 54-190 ng . kg(-1) . min(-1)) and the mean
      duration of high-dose epoprostenol therapy was 1,355 +/- 627 days (range, 582
      2,410 days). Significant decreases from baseline values were seen in mPAP (from
      66 +/- 16 to 47 +/- 12 mmHg, P<0.001) and PVR (from 21.6 +/- 8.3 to 6.9 +/- 2.9
      Wood units, P<0.001). Compared with the baseline state, high-dose epoprostenol
      therapy reduced mPAP by 30% and PVR by 68%. CONCLUSIONS: The present study
      suggests high-dose epoprostenol therapy is a new treatment strategy for IPAH.

PMID- 20697181
TI  - Identification and functional analysis of novel calcium-sensing receptor gene
      mutation in familial hypocalciuric hypercalcemia.
AB  - Familial hypocalciuric hypercalcemia (FHH) is a benign disorder with heterozygous
      inactivating mutations in the calcium-sensing receptor (CASR) gene. The present
      study describes the identification and functional analysis of a novel CASR gene
      mutation leading to FHH. The proband is a 33-yr-old woman (Ca 11.0 mg/dL, intact
      PTH 68 pg/mL, FECa 0.17 %). Leukocyte DNA was isolated in four family members and
      a novel heterozygous mutation (D190G, GAT>GGT) in exon 4 of CASR gene was
      identified by direct sequence analysis. The mutant CASR expression vector was
      constructed by mutagenesis procedure and its response to Ca(2+) was characterized
      by transient transfection into human embryonic kidney (HEK) 293 cells and
      treatment with increasing extracellular Ca(2+) concentrations. HEK cells didn't
      activate intracellular signaling (MAPK activation) in response to increases of
      extracellular Ca(2+) concentrations when the mutant receptor was expressed
      normally at the cell surface. The novel heterozygous mutation (D190G) identified
      in the present study showed that the reduction of activity of CASR to
      extracellular Ca(2+) caused FHH in patients and our study demonstrated the
      importance of Asp-190 participated in response to Ca(2+) in CASR.

PMID- 20697182
TI  - Burnout and perceived stress among university coaches in Lithuania.
AB  - OBJECTIVE: To investigate the associations between burnout, gender, working
      experience and perceived stress among university coaches in Lithuania. METHODS: A
      random sample of university coaches (N=203) was investigated (136 male and 67
      female coaches; 131 coaches, with 10 yr or more work experience, and 72 coaches
      with less than 10 yr job experience). Two questionnaires-the Coach Burnout
      Questionnaire (CBQ) and Perceived Stress Scale-10 (PSS-10)-were used. The
      statistical hypotheses were tested by the independent samples t-test and binary
      logistic regression analysis. RESULTS: Statistically significant differences at
      the 0.01 level for burnout among coaches with 10 yr or more (burnout average
      score and standard deviation 2.28 +/- 0.42), and coaches, who less than 10 yr job
      experience (1.97 +/- 0.35) were found. No differences were observed between males
      and females with regard to burnout. The odds ratio (OR) of perceived stress for
      burnout was 1.92; 95% CI 1.01-3.64. CONCLUSIONS: Significant association between
      burnout and job experience of 10 yr or more as compared to less than 10 yr among
      the university coaches was observed. High levels of perceived stress among
      university coaches are significantly related to burnout.

PMID- 20697183
TI  - Effect of a two-hour training on physicians' skill in interpreting Pneumoconiotic
      chest radiographs.
AB  - OBJECTIVE: Occupational lung diseases have specific radiographic manifestations
      not always well known by physicians. In Japan, asbestos-related diseases became a
      public health concern after the "Kubota Shock", when a number of workers and
      residents living nearby a manufacturer of asbestos-made ducts developed
      mesothelioma caused by asbestos exposure. This preliminary intervention trial
      evaluated the effect of two-hour training on inexperienced physicians' skill in
      interpreting pneumoconiotic chest radiographs. METHODS: One hundred-two Japanese
      physicians participated in two reading-tests, using 12 radiographs, before and
      after the two-hour training with ILO/ICRP and Japan Pneumoconioses Study Group
      (JPSG) reading materials. Physicians had to check for the presence or absence of
      small opacity and pleural plaque consistent with pneumoconiosis. Sensitivity and
      specificity equal or greater than 70% were considered good, 50 to 69% acceptable
      and less than 50%, poor. RESULTS: Post-training improvements in physicians'
      skills were seen. For small opacity, there was an increase in the proportion of
      physicians with good specificity, from 42% to 60%. For pleural plaque, the
      proportion of physicians with good specificity and good sensitivity increased,
      from 60% to 67% and from 18% to 25%, respectively. Also, significant improvements
      were observed in overall sensitivity for pleural plaque, from 46% to 60%
      (p<0.0001), and specificity for small opacity, from 65% to 73% (p<0.0001).
      CONCLUSIONS: This study showed that two-hour participatory training may enhance
      physicians' skill in interpreting pneumoconiotic chest radiographs. There are
      countries without any pneumoconiosis screening program despite the WHO/ILO call
      for worldwide cooperation in eliminating it. Although the two-hour course cannot
      replace the five-day ILO workshop, such a program would be useful in areas with
      environmental or occupational exposure to dust.

PMID- 20697184
TI  - Detection of exaggerated blood pressure response using laboratory of physical
      science protocol and risk of future hypertension.
AB  - OBJECTIVE: To assess the usefulness of the Laboratory of Physical Science (LOPS)
      protocol for detecting exaggerated blood pressure (BP) response as a risk factor
      for future hypertension when controlling for work and personal factors. METHODS:
      Subjects were 815 healthy normotensive men (mean age, 43.1 +/- 6.76 yr; range, 29
      64 yr) who participated in the LOPS protocol, a graded 4-stage exercise test
      undertaken for the measurement of 40-70% of maximum oxygen consumption. A
      hypertensive response was defined as systolic blood pressure (SBP) of 250 mmHg or
      diastolic blood pressure (DBP) of 120 mmHg during the exercise test. RESULTS: New
      onset hypertension or the initiation of antihypertensive drug treatment had
      occurred in 108 men (13.3%) after 7 yr of follow-up. Cox proportional survival
      analysis revealed significantly increased risks of developing hypertension were
      associated with exaggerated BP response to exercise (hazard ratio, 2.3; 95%
      confidence interval, 1.4-3.7) and higher frequency of business trips (hazard
      ratio, 1.7; 95% confidence interval, 1.2-2.5) after multivariable adjustments for
      work and personal-related risk factors. CONCLUSIONS: These results suggest that
      the LOPS protocol is effective for detecting exaggerated BP response as a risk
      factor for future hypertension when controlling for work and personal-related
      risk factors. Exaggerated BP response to exercise and higher frequency of
      business trips are risk factors for developing future hypertension.

PMID- 20697185
TI  - In vitro antimicrobial susceptibility of Brachyspira hyodysenteriae strains
      isolated in Japan from 1985 to 2009.
AB  - The antimicrobial susceptibilities of 72 Brachyspira hyodysenteriae isolates
      collected from clinical cases of swine dysentery (SD) in 11 prefectures in Japan
      between 1985 and 2009 were investigated by an agar dilution method using five
      antimicrobial agents. There is a tendency of Japanese field isolates of B.
      hyodysenteriae to acquire resistance to the main antimicrobials used in SD
      treatment such as tiamulin, valnemulin, and efrotomycin. A responsible approach
      for selection and use of antimicrobial agents is required for SD treatment.

PMID- 20697186
TI  - Distribution of single nucleotide polymorphisms in the CXCR1 gene and association
      with calf diseases in Japanese Black cattle.
AB  - The chemokine (C-X-C) receptor 1 (CXCR1) expressed on the neutrophil surfaces
      interacts primarily with interleukin-8 (IL-8) and has an important role in immune
      response. Two interesting single nucleotide polymorphisms (SNPs), SNP
      CXCR1+777G>C and SNP CXCR1-1768T>A, that exhibit an association with subclinical
      mastitis and milk quality in dairy cattle, respectively, have been reported in
      the bovine CXCR1 gene. The aim of this study was to demonstrate the presence of
      the two SNPs in the CXCR1 gene of Japanese Black cattle and examine the
      association between the SNPs and clinical diseases including intestinal and
      respiratory diseases in calves. Genotyping of the SNPs in healthy Japanese Black
      cattle showed that the SNPs were also present in Japanese Black cattle with gene
      frequencies of 0.37 and 0.15 for the C-type allele in SNP CXCR1+777 and for the A
      type allele in SNP CXCR1-1768, respectively. Statistical analysis of the genotype
      distribution of the SNPs in the bovine CXCR1 gene in healthy and clinical
      intestinal or respiratory diseased Japanese Black cattle indicated no significant
      association of the SNPs with clinical diseases in the calves. However, a
      significant correlation of the number of A alleles in SNP CXCR1-1768 with white
      blood cell (WBC) and platelet counts was found in the disease group. It is
      possible that the SNP in the bovine CXCR1 gene plays a role in modulating the
      hematological profile of WBC and platelet counts.

PMID- 20697187
TI  - [A case of pancreatic neuroendocrine tumor with multiple hepatic metastasis].

PMID- 20697188
TI  - [Diagnosis of gastroesophageal reflux disease: a systematic review].
AB  - The prevalence of gastoesophageal reflux disease (GERD) has been rapidly
      increased in Korea during last 20 years. However, there has been no systematic
      review regarding this disease. The aim of this article was to provide a review of
      available diagnostic modalities for GERD. This review includes proton pump
      inhibitor (PPI) test, endoscopy, ambulatory pH monitoring, impedance pH
      monitoring, and esophageal manometry in order to provide a basis for the
      currently applicable recommendations in the diagnosis of GERD in Korea. With
      weekly heartburn or acid regurgitation, the prevalence of GERD has been reported
      as 3.4% to 7.9%, indicating an increase of GERD in Korea. As the prevalence of
      Barrett's esophagus has been reported to be low, the screening endoscopy for
      Barrett's esophagus is not recommended. Several recent meta-analyses re-evaluated
      the value of the PPI test in patients with typical GERD symptoms and non-cardiac
      chest pain. That is, the PPI test has been proven to be a sensitive tool for
      diagnosing GERD in patients with non-cardiac chest pain and in some preliminary
      trials regarding extraesophageal manifestations of GERD. Ambulatory pH monitoring
      of the esophagus helps to confirm gastroesophageal reflux in patients with
      persistent symptoms (both typical and atypical) in the absence of esophageal
      mucosal damage, especially when a trial of acid suppression has failed. Impedance
      pH test is useful in refractory reflux patients with primary complaints of
      typical GERD symptoms, but this value has not been proved in patients with non
      cardiac chest pain or extraesophageal symptoms. This systematic review is
      targeted to establish the strategy of GERD diagnosis, which is essential for the
      current clinical practice.

PMID- 20697189
TI  - [Diagnosis of functional dyspepsia: a systematic review].
AB  - This review tried to set up an initial diagnostic strategy in patients with
      functional dyspepsia. Dyspepsia was defined as chronic or recurrent pain, or
      discomfort centered in the upper abdomen (i.e., epigastrium), excluding heartburn
      and acute abdominal conditions. We reviewed the available data in order to
      produce currently applicable recommendations for the diagnosis of dyspepsia in
      Korea. Two investigators independently conducted an independent literature search
      of published reports on dyspepsia and diagnosis, including alarm symptoms,
      Helicobacter pylori (H. pylori) test, empirical pharmacological therapy, and
      early upper gastrointestinal (GI) endoscopy. The evidence concerning alarm
      features does not allow clear guideline whether early endoscopy should be
      performed or not. In Asia, including Korea, the prevalence of H. pylori and
      gastric cancer are high. Therefore, 'H. pylori test and treatment' strategy is
      not suitable for the initial diagnostic approach for uninvestigated dyspepsia.
      Long-term empirical pharmacological therapy is not recommended in Korea because
      of the possibility of missing or delaying the diagnosis of gastric cancer. There
      have been a lot of evidences showing that early upper GI endoscopy might be more
      effective than empirical medication, which is different from Western countries.
      However, cut-off age for early endoscopy is not clear, especially in case of
      young age. Further research is necessary to define highrisk age for gastric
      cancer and for a health economic study in the management of patients with
      dyspepsia in Korea.

PMID- 20697191
TI  - [Diagnosis of constipation: a systematic review].
AB  - To diagnose constipation accurately in self-reported constipated patients is very
      important not to miss organic disease and prevent therapeutic abuse. To
      investigate the etiology of functional constipation is also important to
      determine the therapeutic modality of constipation. In this systemic review, the
      clinical usefulness of symptom evaluation, diagnostic tests to rule out organic
      and systemic disease, and functional tests to discriminate underlying
      pathophysiology in the diagnosis of constipation were discussed. No specific
      symptoms or tests were available to predict organic versus functional
      constipation or differentiate slow transit constipation versus evacuation
      disorder. Therefore, collaborative studies are necessary to determine the
      pathophysiology of this disorder.

PMID- 20697190
TI  - [Diagnosis of irritable bowel syndrome: a systematic review].
AB  - Irritable bowel syndrome(IBS) is a very common functional gastrointestinal
      disorder characterized by abdominal discomfort, bloating, and disturbed
      defecation. Patients with IBS have a tendency to visit physicians more frequently
      than those without IBS, thus annual economic consequences of IBS in the Western
      countries are substantial. Therefore, guidelines for the diagnosis and treatment
      of IBS patients have been designed to give a favored effect on the Department of
      Gastroenterology's overall performance. A variety of criteria have been developed
      to identify a combination of symptoms to diagnose IBS, including Manning and Rome
      I, II, and III criteria. Overall, Manning's criteria had a pooled sensitivity and
      specificity, 78% and 72%, respectively. In addition, the Rome I criteria had a
      sensitivity and specificity, 71% and 85%, respectively. However, none described
      the accuracy of Rome II and III yet. Alarm features such as rectal bleeding and
      nocturnal pain offer little discriminative value in separating patients with IBS
      from those with organic diseases. Even though anemia and weight loss have poor
      sensitivity for organic diseases, they offer very good specificity. Since
      specific biomarker of IBS is not yet available, diagnostic tests are frequently
      performed to exclude organic diseases. However, the accuracy of diagnostic tests
      is disappointing. CBC, chemistry, thyroid function test, stool exam,
      ultrasonography, hydrogen breath test, erythrocyte sedimentation rate, and C
      reactive protein have all very limited accuracy in discriminating IBS from
      organic diseases. This systemic review is targeted to establish the strategy of
      IBS treatment, which is very necessary for the current clinical practice.

PMID- 20697192
TI  - [Gastritis cystica profunda accompanied by multiple early gastric cancers].
AB  - Gastritis cystica profunda (GCP) is a rare disease which shows multiple cystic
      gastric glands within the submucosa of the stomach. GCP lesions mainly develop at
      the site of gastroenterostomy and exhibit benign behavior. However, there have
      been a number of debates over its malignant potential. Several reports have
      documented GCP accompanied by gastric carcinomas, but the relationship between
      the two conditions remains uncertain. Here we report two cases of GCP with
      dysplasia accompanied by synchronous multiple early gastric cancers without
      previous gastric surgery.

PMID- 20697193
TI  - [A case of limited Wegener's granulomatosis with gastroenteritis and mesenteric
      lymphadenopathy].
AB  - Wegener's granulomatosis (WG) is a disease characterized by a granulomatous
      necrotizing vasculitis of small vessels. Although any organ systems can be
      involved, gastrointestinal involvement in WG is notably uncommon. We present a
      case of 67-year-old man who was admitted with abdominal pain and diarrhea lasting
      for 3 weeks. Colonoscopy and abdominal CT scan revealed vasculitis and multiple
      mesenteric lymphadenopathy. Jejunum and mesenteric lymph nodes biopsies confirmed
      limited form of WG. The present case indicates that WG might involve only
      gastrointestinal tract and the histological confirmation is important for
      diagnosis.

PMID- 20697194
TI  - [A case of ulcerative colitis found in a patient whose parent has Crohn's
      disease].
AB  - Inflammatory bowel diseases (IBD) is heterogeneous, chronic relapsing disorder.
      Inappropriate and exaggerated immune response for the luminal antigen is known as
      a main pathogenesis. Genetic, infectious, and environmental factors are
      responsible for unbalanced immune response, but the definite pathogenesis is
      still unclear. Genetic factor is the most important role of all. That is based on
      high concordance rate of identical twins and family history. The incident rate
      and prevalence of IBD for the Asian population is relatively lower than Western
      population, and the lack of NOD2 or TLR4 genetic polymorphisms in Korea and
      Japanese population suggests the difference in genetic background between Asian
      and Western population. In Korea, the case of familial aggregation of IBD is
      pretty rare. We report a case of the daughter with ulcerative colitis and her
      mother with Crohn's disease who have a -159C/T promoter polymorphism of CD14 gene
      for IBD.

PMID- 20697195
TI  - [Interstitial lung disease associated with combination chemotherapy of
      oxaliplatin, 5-fluorouracil, and leucovorin].
AB  - Oxaliplatin with 5-fluorouracil plus leucovorin (FOLFOX) has become the standard
      treatment in patients with colorectal cancer. Among known toxicities induced by
      oxaliplatin, hematological, gastrointestinal and neurological toxicities are
      common. However, acute pulmonary toxicity associated with oxaliplatin is unusual.
      One case of interstitial lung disease associated with the FOLFOX protocol is
      reported here.

PMID- 20697196
TI  - Dose/dense metronomic chemotherapy with fractioned cisplatin and oral daily
      etoposide enhances the anti-angiogenic effects of bevacizumab and has strong
      antitumor activity in advanced non-small-cell-lung cancer patients.
AB  - BACKGROUND: We designed a translational clinical trial to investigate whether a
      dose/dense chemotherapy regimen is able to enhance in patients with non-small
      cell-lung-cancer (NSCLC) the anti-angiogenic effects of bevacizumab, a
      murine/human monoclonal antibody to the vasculo-endothelial-growth-factor (VEGF).
      We also evaluated the antitumor activity of this combination. RESULTS: The
      combined treatment induced a significant decline in the blood-perfusion of
      primary tumor (NMR-study); in serum levels of VEGF, angiopoietin-1,
      thrombospondin-1; and in the number of VEGF-transporting cells. In the group of
      40 patients who received bevacizumab an objective response and a disease
      stabilization rate of 77.5% (95% CI, 75.63-93.17) and 15%, respectively, were
      recorded with a time to progression of 7.6 mo. Grade I-II hematological toxicity
      was the most common adverse event. Four early deaths within 3 mo, three cases of
      pneumonia, and six cases of mood depression at higher bevacizumab dosage were
      observed. The most active biological and maximum tolerated dose were 5 and 7.5
      mg/kg, respectively. PATIENTS AND METHODS: Forty-eight patients (42 males and six
      females) with stage III B/IV NSCLC, a mean age of 68 y, and ECOG <or=2 were
      enrolled in the study. They received every 3 w fractioned cisplatinum (30 mg/sqm,
      days 1-3) and oral etoposide (50 mg, days 1-15) and were divided in five cohorts
      receiving different bevacizumab dosages (0; 2.5; 5; 7.5; and 10 mg/kg) on day 3.
      CONCLUSION: The combination of bevacizumab with a dose/dense chemotherapy regimen
      resulted moderately safe but showed significant anti-angiogenic and antitumor
      activity.

PMID- 20697198
TI  - Histone H2AX: The missing link in AIF-mediated caspase-independent programmed
      necrosis.
AB  - Caspase-independent programmed necrosis is a highly regulated cellular demise
      that displays morphological and biochemical necrotic hallmarks, such as an
      earlier permeability of the plasma membrane and lactate dehydrogenase (LDH)
      leakiness. This form of programmed cell death (PCD) is regulated by AIF, a FAD
      dependent oxidoreductase, which is released from the mitochondria to the nucleus
      where it induces chromatin tcondensation and DNA fragmentation. Some years ago,
      it was established that the sequential activation of poly(ADP-ribose) polymerase-
      1 (PARP-1), calpains and Bax regulates the mitochondrial AIF release associated
      to programmed necrosis. But, what happens when AIF is in the nucleus? How does
      this protein induce chromatinolysis and programmed necrosis? Recently, we have
      unraveled some of the mechanisms underlying the nuclear action of AIF in this
      type of caspase-independent cell death. Indeed, AIF plays a key role in
      programmed necrosis by its ability to organize a DNA-degrading complex with H2AX
      and Cyclophiline A (CypA). The AIF/H2AX link is indeed a critical event and
      explains the nuclear AIF apoptogenic action. In the present article, we outline
      the current knowledge on cell death by programmed necrosis and discuss the
      relevance of the AIF/H2AX/CypA DNA-degrading complex in the regulation of this
      original form of cell death.

PMID- 20697199
TI  - Nutrient sensing and insulin signaling in neuropeptide-expressing immortalized,
      hypothalamic neurons: A cellular model of insulin resistance.
AB  - Obesity and type 2 diabetes mellitus represent a significant global health
      crisis. These two interrelated diseases are typified by perturbed insulin
      signaling in the hypothalamus. Using novel hypothalamic cell lines, we have begun
      to elucidate the molecular and intracellular mechanisms involved in the
      hypothalamic control of energy homeostasis and insulin resistance. In this
      review, we present evidence of insulin and glucose signaling pathways that lead
      to changes in neuropeptide gene expression. We have identified some of the
      molecular mechanisms involved in the control of de novo hypothalamic insulin mRNA
      expression. And finally, we have defined key mechanisms involved in the etiology
      of cellular insulin resistance in hypothalamic neurons that may play a
      fundamental role in cases of high levels of insulin or saturated fatty acids,
      often linked to the exacerbation of obesity and diabetes.

PMID- 20697200
TI  - Combined Haemophilus influenzae type b and Neisseria meningitidis serogroup C
      (HibMenC) or serogroup C and Y-tetanus toxoid conjugate (and HibMenCY) vaccines
      are well-tolerated and immunogenic when administered according to the 2,3,4
      months schedule with a fourth dose at 12-18 months of age.
AB  - Combined HibMenCY and HibMenC conjugate vaccines may facilitate inclusion of
      vaccination against MenC and MenY into routine vaccination schedules, without
      additional injections. Immunogenicity and reactogenicity of vaccination with
      three different formulations of a novel HibMenCY-conjugate vaccine, or a HibMenC
      conjugate vaccine was assessed. Infants were randomized to receive either Hib(2.5
      ug)-MenC(5 ug)-MenY(5 ug)-TT, Hib(5 ug)-MenC(10 ug)-MenY(10 ug)-TT, Hib(5 ug)
      MenC(5 ug)-MenY(5 ug)-TT or Hib(5 ug)-MenC(5 ug)-TT vaccines co-administered with
      DTPa-HBV-IPV at 2-3-4 months of age. Controls received licensed conjugate MenC
      CRM197 vaccine co-administered with DTPa-HBV-IPV/Hib. A fourth dose was
      administered to a subset of children at age 12-18 months. Anti-PRP concentrations
      and meningococcal bactericidal (rSBA-MenC/Y) titres were measured prior to and
      one month post third and fourth vaccination dose. Solicited local, general
      symptoms and unsolicited adverse events were recorded for 7 and 30 days after
      each vaccination, respectively. Post dose 3, all subjects had anti-PRP antibody
      levels >= 0.15 ug/ml and rSBA-MenC >= 1:8. 97.0%-98.6% of HibMenCY recipients had
      rSBA-MenY >= 1:8. Pre-dose-4, 95.6%-100% of HibMenCY and HibMenC recipients had
      anti-PRP >= 0.15 ug/ml and 90.7%-97.6% recipients had rSBA-MenC titres >= 1:8. In
      HibMenCY groups, 78.6%-86.7% had persisting rSBA-MenY >= 1:8. The post-dose-4
      response was robust after all vaccines with all subjects having anti-PRP >= 1
      ug/ml and 92.3%-100% rSBA-MenC >= 1:128. All HibMenCY recipients had rSBA-MenY >=
      1:128. Vaccination with the novel Hib-meningococcal vaccines had a safety profile
      similar to control. HibMenCY and HibMenC conjugate vaccine formulations given at
      2-3-4 months of age with a fourth dose in the second year of life were
      immunogenic and had a comparable safety profile to licensed vaccines. (study
      792014 and 100381;www.clinicaltrial.govID:NCT00129116)

PMID- 20697201
TI  - Life without geminin.
AB  - The interplay of proliferation and differentiation is essential for normal
      development and organogenesis. Geminin is a cell cycle regulator which controls
      licensing of origins for DNA replication, safeguarding genomic stability. Geminin
      has also been shown to regulate cellular decisions of self-renewal versus
      commitment of neuronal progenitor cells. We discuss here our recent analysis of
      mice with conditional inactivation of the Geminin gene in the immune system. Our
      data indicate that Geminin is not indispensable for every cell division: in the
      absence of Geminin, development of progenitor T cells appears largely unaffected.
      In contrast, rapid cell divisions, taking place in vitro upon TCR receptor
      activation or in vivo during homeostatic proliferation, are defective.

PMID- 20697206
TI  - Advances in economics to further inform investments in vaccine development.

PMID- 20697207
TI  - Evolution of CST function in telomere maintenance.
AB  - Telomeres consist of an elaborate, higher-order DNA architecture, and a suite of
      proteins that provide protection for the chromosome terminus by blocking
      inappropriate recombination and nucleolytic attack. In addition, telomeres
      facilitate telomeric DNA replication by physical interactions with telomerase and
      the lagging strand replication machinery. The prevailing view has been that two
      distinct telomere capping complexes evolved, shelterin in vertebrates and a
      trimeric complex comprised of Cdc13, Stn1 and Ten1 (CST) in yeast. The recent
      discovery of a CST-like complex in plants and humans raises new questions about
      the composition of telomeres and their regulatory mechanisms in multicellular
      eukaryotes. In this review we discuss the evolving functions and interactions of
      CST components and their contributions to chromosome end protection and DNA
      replication.

PMID- 20697208
TI  - Leucine supplementation augments insulin secretion in pancreatic islets of
      malnourished mice.
AB  - OBJECTIVES: We investigated the influence of leucine supplementation on insulin
      secretion and on some proteins related to insulin secretion in malnourished mice.
      METHODS: Swiss mice (aged 21 days) received isocaloric normo-17% (NP) or 6% low
      protein (LP) diet for 120 days. Half of the NP and LP mice received 1.5% leucine
      in the drinking water during the last 30 days (NPL and LPL, respectively).
      RESULTS: The LP mice were hypoinsulinemic compared with the NP group, whereas LPL
      mice exhibited increased insulinemia in the fed state versus LP mice. The LP
      mouse islets were less responsive to 22.2 mM glucose, 100 microM carbachol (Cch),
      and 10 mM leucine than the NP group. However, LPL islets were more responsive to
      all these conditions compared with the LP group. The muscarinic type 3 receptor,
      (M3R) Cabeta2, and PKC-alpha protein contents were reduced in LP compared with NP
      islets but significantly higher in LPL than LP islets. The p-AKT/AKT ratio was
      higher in LPL compared with LP islets. CONCLUSIONS: Leucine supplementation
      increases insulin secretion in response to glucose and leucine and to agents that
      potentiate secretion, such as Cch, in malnourished mice. The enhanced levels of
      M3R, Cabeta2, and PKC-alpha proteins, as well as of the p-AKT/AKT ratio, may play
      a role in this process.

PMID- 20697209
TI  - Inhibition of arginase activity ameliorates L-arginine-induced acute pancreatitis
      in rats.
AB  - OBJECTIVES: Intraperitoneal (IP) injection of 3.5 g/kg L-arginine (known to
      induce acute pancreatitis) in rats will result in much greater increases in serum
      ornithine versus citrulline concentration (Crit Care Med. 2008;36:2117-2127).
      These data indicate a major role of arginase in the catabolism of L-arginine.
      Therefore, we tested the effects of the irreversible arginase inhibitor (+)-S-2
      amino-6-iodoacetamidohexanoic acid (AIHA) on L-arginine-induced acute
      pancreatitis. METHODS: The inhibitory effect of AIHA on arginase activity was
      tested on rat liver homogenate and purified bovine arginase. Male Wistar rats
      were administered 15 mg/kg AIHA or its vehicle IP 1 hour before the injection of
      physiological saline or 3.5 g/kg L-arginine IP. Laboratory and histological
      parameters of pancreatitis were determined 24 hours after the last injection.
      RESULTS: Sixty micromolars of AIHA (equimolar to an in vivo dose of 15 mg/kg)
      significantly inhibited arginase activity by about 25%. Pretreatment with AIHA
      significantly ameliorated pancreatic damage caused by L-arginine administration.
      It decreased pancreatic weight/body weight ratio, pancreatic glutathione
      peroxidase and myeloperoxidase activities, and histological damage.
      Administration of AIHA in itself significantly increased levels of pancreatic
      heat shock proteins. CONCLUSIONS: Pretreatment with AIHA reduces the severity of
      L-arginine-induced pancreatitis most likely by inhibiting arginase activity.

PMID- 20697210
TI  - Investigation of relaxant effects of new agents affecting nitric oxide/cyclic
      guanosine monophosphate pathway on sheep oddi sphincter.
AB  - OBJECTIVES: Nitric oxide (NO) is a potent nonadrenergic, noncholinergic mediator
      of gastrointestinal smooth muscle. We aimed to investigate the effects of new
      NO/cyclic guanosine monophosphate (cGMP) pathway-affecting agents at the sheep
      sphincter of Oddi (SO) in vitro. METHODS: Sheep SO rings were mounted in organ
      baths and tested for isometric tension and cGMP levels in response to 3,3
      bis(aminoethyl)-1-hydroxy-2-oxo-1-triazene; 3-morpholinosydnonimine hydrochloride
      (SIN-1); and BAY 41-2272 in the presence and absence of 1H-(1,2,4)oxadiazole(4,3
      a)quinoxalin-1-one (ODQ). RESULTS: 3,3-bis(Aminoethyl)-1-hydroxy-2-oxo-1
      triazene; SIN-1; and BAY 41-2272 relaxed SO rings in a concentration-dependent
      manner. These relaxations were significantly decreased in the presence of ODQ (P
      < 0.05). All agents significantly increased the cGMP levels compared with the
      control group (P < 0.05). The increased cGMP levels in the 3,3-bis(aminoethyl)-1
      hydroxy-2-oxo-1-triazene- and BAY 41-2272-treated groups were significantly
      different from both control and carbachol groups (P < 0.05), whereas the increase
      in the SIN-1 group was significantly different from all groups (P < 0.05). The
      cGMP levels were significantly lower in the presence of ODQ compared with its
      absence (P < 0.05). CONCLUSIONS: The relaxation of SO rings by these agents may
      be via increasing the levels of cGMP. The additional increase produced by SIN-1
      may be the combined effects of NO generation and activation of guanylyl cyclase.

PMID- 20697211
TI  - Endless opportunities.

PMID- 20697214
TI  - Neonatal care at the moment of birth: using simulation to prepare the nurse.
AB  - Successful transition of the neonate from the intrauterine environment to the
      extrauterine world is a complex and unique process. The assessments and
      interventions of the nurse during these precious moments following birth have a
      dramatic impact on the well-being of the neonate. This article reports on the
      development and implementation of a nursing situation simulation focused on
      educating nurses for this role. Simulation has been shown to increase confidence
      and competence of nurses. Use of simulation allows nurses to gain experience
      without placing the patient at risk.

PMID- 20697215
TI  - A data-driven approach to retinopathy of prematurity prevention leads to dramatic
      change.
AB  - Retinopathy of prematurity (ROP) is a common disease of premature infants. It is
      characterized by an abnormal proliferation of blood vessels in the developing
      retina and is the leading cause of childhood blindness in developed countries.
      This article describes a systematic approach to prospectively reduce the
      incidence of ROP in a newborn intensive care unit (NICU). We realized the need
      for improvement when we reviewed comparative data indicating that our rates of
      ROP were higher than those in NICUs in our local area, across the United States,
      and around the world. After informal efforts appeared successful in significantly
      reducing ROP, we designed and implemented a more structured approach to ROP
      prevention that included improvements in practice related to oxygen
      administration and monitoring. An evidence-based guideline was developed, and
      education was provided to all direct care providers. We also standardized bedside
      oxygen delivery equipment and implemented new parameters related to nasal cannula
      weaning. Rates of ROP, severe ROP, and ROP requiring surgical intervention were
      reduced by more than 50% during the first year and more than 75% by the end of
      the second year after implementation of our unit-based program.

PMID- 20697216
TI  - Understanding neurodevelopmental outcomes of prematurity: education priorities
      for NICU parents.
AB  - NICU nurses have an important role to play in many aspects of parent education.
      This article stresses the need for an increased focus on teaching parents about
      the central role that self-regulation will play in their infant's neurobehavioral
      development not only during the early infancy period but throughout all of
      childhood and adolescence. Suggestions are made about how to conceptualize the
      relation between cognition and emotions in humans and how to help parents
      understand that continued vigilance concerning potential problems in attention
      and self-regulation will be necessary.

PMID- 20697218
TI  - Flight physiology: science of air travel with neonatal transport considerations.
AB  - Air transportation, by rotor wing and fixed wing, is a frequent method of
      neonatal transportation. There are many risks involved in air transportation. It
      is well documented that the safety of rotor wing flights has been questioned.
      Fixed wing transport is viewed as a safer mode of transportation. Air
      transportation has risks other than vehicle accidents, and increasing altitude
      encountered in both fixed and rotor wing transportation can cause significant
      distress to both the transport crew and the patient. Knowledge and awareness of
      these risks by the flight team can help to alleviate unnecessary risks and
      complications encountered during air transportation and ensure a safe arrival of
      both the team and the patient.

PMID- 20697219
TI  - Forgotten parent: NICU paternal emotional response.
AB  - PURPOSE: To evaluate and compare the presence of perceived paternal stress and
      depressive symptomatology in fathers of preterm infants over time. SUBJECTS:
      Fathers of NICU infants born before 30 weeks of gestation. DESIGN: Prospective
      convenience sample. METHODS: Consenting fathers were given 2 self-report
      questionnaires: Center for Epidemiologic Studies-Depression Scale (CES-D) and
      Parent Stressor Scale: Infant Hospitalization (PSS:IH) on 7th (time 1), 21st
      (time 2), and 35th (time 3) days of life. Objective measurement of illness
      severity was quantified by Score for Neonatal Acute Physiology. Statistical
      methods included generalized linear estimating equation and mixed linear
      modeling. MAIN OUTCOME MEASURES: Stress and depressive symptomatology in fathers
      of preterm infants. RESULTS: Stress scores (PSS:IH) were unchanged over time (P =
      .62) indicating that fathers (n = 35) remain significantly stressed. Individual
      subcomponents of stress (parent role alteration, infant appearance/behavior, NICU
      sights/sounds) also remained constant over the study period (P = .05 for each).
      Stress scores over time were not modified by demographic characteristics
      (marriage, education, insurance). Mean depressive symptomatology scores (CES-D)
      decreased over time (P = .04). The percentage of fathers with elevated CES-D
      scores (>16) decreased from a baseline 60% but did not diminish between times 2
      (39%) and 3 (36%). Parent Stressor Scale: Infant Hospitalization stress scores
      were correlated with CES-D depressive symptomatology scores (P < .01).
      Socioeconomic factors influenced initial CES-D scores, but only marriage
      ameliorated subsequent changes in measurements. Objective measurement of infant
      illness (Score for Neonatal Acute Physiology) did not influence paternal CES-D or
      PSS:IH scores. CONCLUSION: Fathers of premature infants in a medical NICU
      demonstrated elevated levels of stress that persisted across time for all domains
      of measured stress. Paternal self-reported stress and depressive symptomatology
      was independent of infant illness. One third of fathers had persistently elevated
      CES-D scores. If these findings are representative of general NICU population,
      then the emotional needs of our fathers are not being fully addressed.

PMID- 20697220
TI  - To splint or not to splint: securing the peripheral intravenous cannula.

PMID- 20697221
TI  - A pilot study to determine the safety and feasibility of oropharyngeal
      administration of own mother's colostrum to extremely low-birth-weight infants.
AB  - Own mother's colostrum is rich in cytokines and other immune agents that may
      stimulate oropharyngeal-associated lymphoid tissue if administered
      oropharyngeally to extremely low-birth-weight (ELBW) infants during the first
      days of life when enteral feeding is contraindicated. However, the safety and
      feasibility of the oropharyngeal route for the administration of colostrum have
      not been determined. PURPOSE: To determine the safety of oropharyngeal
      administration of own mother's colostrum to ELBW infants in first days of life. A
      secondary purpose was to investigate the feasibility of (1) delivering this
      intervention to ELBW infants in the first days of life and (2) measuring
      concentrations of secretory immunoglobulin A and lactoferrin in tracheal aspirate
      secretions and urine of these infants. SUBJECTS: Five ELBW infants (mean birth
      weight and gestational age = 657 g and 25.5 weeks, respectively). DESIGN: Quasi
      experimental, 1 group, pretest-posttest design. METHODS: Subjects received 0.2 mL
      of own mother's colostrum administered oropharyngeally every 2 hours for 48
      consecutive hours, beginning at 48 hours of life. Concentrations of secretory
      immunoglobulin A and lactoferrin were measured in tracheal aspirates and urine of
      each subject at baseline, at the completion of the intervention and again 2 weeks
      later. RESULTS: All infants completed the entire treatment protocol, each
      receiving 24 treatments. A total of 15 urine specimens were collected and 14 were
      sufficient in volume for analysis. A total of 15 tracheal aspirates were
      collected, but only 7 specimens (47%) were sufficient in volume for analysis.
      There was wide variation in concentrations of secretory immunoglobulin A and
      lactoferrin in urine and tracheal aspirates among the 5 infants; however, several
      results were outside the limits of assay detection. All infants began to suck on
      the endotracheal tube during the administration of colostrum drops. Oxygen
      saturation measures remained stable or increased slightly during each of the
      treatment sessions. There were no episodes of apnea, bradycardia, hypotension, or
      other adverse effects associated with the administration of colostrum.
      CONCLUSIONS: Oropharyngeal administration of own mother's colostrum is easy,
      inexpensive, and well-tolerated by even the smallest and sickest ELBW infants.
      Future research should continue to examine the optimal procedure for measuring
      the direct immune effects of this therapy, as well as the clinical outcomes such
      as infections, particularly ventilator-associated pneumonia.

PMID- 20697223
TI  - Nephrogenic gadolinium biodistribution and skin cellularity following a single
      injection of Omniscan in the rat.
AB  - OBJECTIVES: The development of nephrogenic systemic fibrosis (NSF) following MRI
      contrast examination has been associated with gadolinium (Gd) toxicity. Animal
      models should show the key features of NSF in man where, the only immutable
      epidemiological feature is renal impairment. A rat model of chronic renal
      insufficiency has been employed to establish whether tissue gadolinium retention
      and increased skin cellularity following a gadolinium based contrast agent (GBCA)
      can be correlated with a reduction in renal function. The GBCA chosen for
      investigation was Omniscan, the least stable of the commercially available
      agents. MATERIALS AND METHODS: Wistar rats were subjected to 5/6 subtotal
      nephrectomy (SNx) under isoflurane anesthesia. The glomerular filtration rate
      (GFR) was assessed from serum creatinine and creatinine clearance. Two SNx rats
      groups were established, following either 75% or 80% resection of the kidney,
      which reduced the GFR down to 40% and down to 20%, respectively, of sham-operated
      controls. Three months after surgery, rats received a single intravenous
      injection of either saline or Omniscan (gadodiamide 2.5 mmol/kg). Four weeks
      later, the Gd content of serum, skin, liver, and bone was measured by inductively
      coupled plasma mass spectrometry and skin cellularity determined. RESULTS: In
      sham-operated rats, Gd was detected in skin < liver < bone. SNx rats with the GFR
      reduced down to 20% normal, had an increased tissue Gd concentration in bone (2.5
      fold), skin (3-fold), and liver (10-fold) compared with sham-operated controls.
      The Gd concentration in all 3 tissues showed a positive linear correlation with
      serum creatinine (P < 0.01). No external skin lesions were observed. The skin
      cellularity of rats with the GFR reduced down to 20% of normal was increased
      following Omniscan, together with positive immunostain for CD34 and prolyl-4
      hydroxylase. CONCLUSIONS: The SNx rat is a sensitive model for investigating the
      pathophysiology of NSF. A positive linear correlation was obtained between tissue
      Gd and serum creatinine, the major clinical marker of renal function. An increase
      in skin cellularity, a feature of human NSF, was demonstrated in rats with a
      level of renal impairment equivalent of stage 4 chronic kidney disease following
      just a single intravenous dose of Omniscan. This response was obtained in the
      absence of ulcerogenic skin lesions, at skin Gd concentrations as low as 50
      nmol/g.

PMID- 20697224
TI  - Intravenous versus intra-articular delayed gadolinium-enhanced magnetic resonance
      imaging in the hip joint: a comparative analysis.
AB  - OBJECTIVE: The purpose of this study was to investigate whether T1-mapping of hip
      joint with intra-articular delayed gadolinium-enhanced magnetic resonance imaging
      (MRI) of cartilage (ia-dGEMRIC) is comparable to the already established
      intravenous (iv)-technique for assessing different grades of cartilage
      degeneration. MATERIALS AND METHODS: The study cohort consisted of 53 patients
      with symptomatic femoroacetabular impingement (FAI) that were randomly recruited
      for either iv-dGEMRIC or ia-dGEMRIC studies. RI was performed in supine position
      at a 1.5 Tesla (T) system (Magnetom Avanto, Siemens, Erlangen, Germany) using a
      body matrix-phased array coil. Twenty-six patients (18 males, 8 females; mean age
      +/- standard deviation [SD]: 32.1 +/- 8.8 years, range: 17-49 years) underwent iv
      dGEMRIC whereas 27 patients (17 males, 10 females; mean age 34.0 +/- 10.8 years,
      range: 13.0-57 years) underwent ia-dGEMRIC mapping. On average patients suffered
      from FAI for 23.9 +/- 20.9 months in the iv-dGEMRIC group (range: 5-108 months)
      whereas FAI was symptomatic for 20.9 +/- 25.2 months in the ia-dGEMRIC group
      (range: 3-120 months). Patient demographics and symptomatology in both groups
      were not statistically different. RESULTS: Mapping with both techniques (iv and
      ia) demonstrated appropriately similar differences between various grades of
      cartilage degeneration. Overall, there was no significant difference between iv
      dGEMRIC and ia-dGEMRIC T1 mean values in all grades of cartilage findings (P:
      0.394, 0.400, and 0.173). Of note, the T1 values after iv-dGEMRIC were higher
      (544.3 +/- 104.2 milliseconds) in regions with cartilage damage extent <0.75 cm
      than in regions where no damage was noted (535.7 +/- 112.4 milliseconds). After
      ia-dGEMRIC the T1 values were similar (521.2 +/- 125.1 milliseconds vs. 521.1 +/-
      94.3 milliseconds). CONCLUSIONS: Intravenous contrast remains the standard method
      of contrast administration in the current scenario when dGEMRIC imaging is
      performed. Our results demonstrate that the information and mapping values
      obtained by the ia-technique are similar to those of the iv-technique. The
      intravenous route can have its own problems in certain patients with impaired
      renal function tests or when parenteral access is an issue in many patients.
      Intra-articular technique could be a good alternative in such cases whereas
      maintaining the quality of imaging and obtained information. Thus, in well
      selected cases ia-dGEMRIC mapping may be a potential alternative to iv-dGEMRIC
      for hip joint cartilage analysis. LEVEL OF EVIDENCE: Prospective case series,
      Diagnostic study comparing different modalities of assessing status of hip joint
      cartilage: Level II evidence.

PMID- 20697225
TI  - Gadolinium-based magnetic resonance contrast agents at 7 Tesla: in vitro T1
      relaxivities in human blood plasma.
AB  - PURPOSE/INTRODUCTION: The aim of this study was to determine the T1 relaxivities
      (r1) of 8 gadolinium (Gd)-based MR contrast agents in human blood plasma at 7
      Tesla, compared with 3 Tesla. SUBJECTS AND METHODS: Eight commercially available
      Gd-based MR contrast agents were diluted in human blood plasma to concentrations
      of 0, 0.25, 0.5, 1, and 2 mmol/L. In vitro measurements were performed at 37
      degrees C, on a 7 Tesla and on a 3 Tesla whole-body magnetic resonance imaging
      scanner. For the determination of T1 relaxation times, Inversion Recovery
      Sequences with inversion times from 0 to 3500 ms were used. The relaxivities were
      calculated. RESULTS: The r1 relaxivities of all agents, diluted in human blood
      plasma at body temperature, were lower at 7 Tesla than at 3 Tesla. The values at
      3 Tesla were comparable to those published earlier. Notably, in some agents, a
      minor negative correlation of r1 with a concentration of up to 2 mmol/L could be
      observed. This was most pronounced in the agents with the highest protein-binding
      capacity. DISCUSSION/CONCLUSION: At 7 Tesla, the in vitro r1 relaxivities of Gd
      based contrast agents in human blood plasma are lower than those at 3 Tesla. This
      work may serve as a basis for the application of Gd-based MR contrast agents at 7
      Tesla. Further studies are required to optimize the contrast agent dose in vivo.

PMID- 20697228
TI  - Heat-related illnesses: opportunities for prevention.

PMID- 20697229
TI  - The effects of age and shift work on perceived sleep problems: results from the
      VISAT-combined longitudinal and cross-sectional study: Retraction.

PMID- 20697232
TI  - Journal of Perinatal & Neonatal Nursing. From the editors.

PMID- 20697233
TI  - Understanding and explaining risk.

PMID- 20697234
TI  - Why having an attitude of innovation is important in the neonatal intensive care
      unit.

PMID- 20697235
TI  - Probiotics are food; herbs are plants; what's the risk? Informed consent for
      complementary and integrative therapies.

PMID- 20697236
TI  - Internet resources.

PMID- 20697237
TI  - Exploring the role of uterine artery embolization in the management of postpartum
      hemorrhage.
AB  - Postpartum hemorrhage is a potentially life-threatening obstetric emergency that
      requires prompt nursing and medical interventions. In the majority of cases,
      initial strategies such as fundal massage and uterotonic medications will
      effectively stop excessive bleeding. Unfortunately, the incidence and severity of
      postpartum hemorrhage are on the rise and peripartum hysterectomy remains a life
      saving intervention in cases of intractable bleeding. As an emerging alternative
      to hysterectomy, uterine artery embolization (UAE) has demonstrated success rates
      of more than 90% in controlling postpartum hemorrhage unresponsive to other
      therapies. Research to date has shown UAE to be a safe, minimally invasive
      procedure with few reported complications and minimal effects on future
      fertility. For patients who are hemodynamically stable with access to an
      interventional radiology suite, UAE is an important consideration in the
      treatment of severe postpartum bleeding. This article explores the role of UAE as
      a part of this management algorithm. The technical aspects of this procedure,
      reported complications, and effects on future fertility are described. The
      prophylactic use of intra-arterial balloon catheters in the management of
      abnormal placentation is also discussed.

PMID- 20697238
TI  - Active versus expectant management of the third stage of labor and implementation
      of a protocol.
AB  - Although the focus at delivery may naturally shift to infant transition,
      continued maternal vigilance during stage 3 is imperative to accomplish a safe
      outcome for the mother and her newborn. The third stage of labor is a normal
      physiological progression of birth that may be compounded by serious
      complications. The most common complication is postpartum hemorrhage due to
      uterine atony. Clinicians choose either active management or expectant management
      for stage 3 to prevent excessive maternal blood loss. Rapid identification and
      response to a postpartum hemorrhage are critical. A multidisciplinary perinatal
      team at a large Midwest tertiary center led the transition from an expectant to
      an active-management protocol within the obstetric service. Outcomes included a
      decrease in the postpartum hemorrhage rate and decreased usage of additional
      uterotonic medications during the immediate recovery period.

PMID- 20697240
TI  - ST analysis as an adjunct to electronic fetal monitoring: an overview.
AB  - Conventional electronic fetal monitoring in the United States has value as a
      screening tool but is extremely limited as a diagnostic tool. ST analysis was
      developed as an adjunctive technology, able to measure changes in the ST segment
      of the fetal electrocardiogram during periods of hypoxia, improving the
      identification of the fetus at risk for metabolic acidemia at birth. Currently
      used only in a handful of hospitals in the United States, studies abroad have
      demonstrated that an integrated approach utilizing electronic fetal monitoring,
      ST analysis, and standardized guidelines in a selected patient population can
      improve neonatal outcome, decrease acidemia at birth, and decrease obstetric
      operative delivery. Research is needed to determine whether similar results are
      possible in the US population.

PMID- 20697241
TI  - The uses of aromatherapy in women's health.
AB  - Aromatherapy is the practice of therapeutic use of essential plant-based oils.
      Essential oils and aromatherapy have been used in the care of women for
      centuries. The published research has used small samples and often combines other
      complementary therapies with aromatherapy; however, the use of essential oils has
      not been shown to cause harm and is accepted by women. Aromatherapy mixtures are
      appropriate for use by nurses in labor and delivery settings. The article reviews
      the literature and discusses appropriate essential oil mixtures for use in
      women's health setting and labor and delivery.

PMID- 20697242
TI  - An innovative model for achieving breast-feeding success in infants with complex
      surgical anomalies.
AB  - This manuscript describes an innovative nurse-driven continuous quality
      improvement project. Infants born with congenital surgical anomalies face
      significant challenges within the newborn period and human milk/breast-feeding
      may not be viewed as a priority. In many hospitals, nurses refer families to
      lactation consultants for all breast-feeding assistance and support. The
      Transition to Breast Pathway was developed on the basis of the evidence-based
      standards and protocols at The Children's Hospital of Philadelphia. The pathway
      consists of (1) initiation of pumping and maintenance of milk supply, (2) mouth
      care with human milk, (3) skin-to-skin care, (4) nonnutritive sucking at the
      breast, (5) transitioning to at breast feeds. A sample of 80 infants were
      enrolled in this project. Major results of the project are as follows: (1)
      mother's average milk supply was approximately 603 mL/d, (2) 71% (57/80) of the
      infants received mouth care with human milk, (3) 48% (38/80) mother/infant dyads
      performed skin-to-skin care, (4) 60% (35/58) of mother/infant dyads performed
      nonnutritive sucking at the breast, (5) 100% (58/58) of mother-infant dyads
      transitioned to breast prior to discharge. This continuous quality improvement
      project demonstrates that nurses can and should lead the process of transitioning
      infants to at breast feeds.

PMID- 20697244
TI  - Magnetic resonance imaging studies without sedation in the neonatal intensive
      care unit: safe and efficient.
AB  - Use of magnetic resonance imaging (MRI) in the neonatal intensive care unit has
      been increasing over the past several years because of improved MRI technology
      and increased clinical awareness of the prognostic and diagnostic information
      available. Historically, the use of sedation has been the standard for achieving
      quality imaging without motion artifact, but it exposed the patient to risks
      associated with sedation medications. In an effort to obtain MRI studies with
      elimination of risks associated with sedation, a quality improvement project was
      initiated. Implementing a standardized approach utilizing a vacuum immobilizer
      has led to successful neonatal MRI completion without the need for sedation in
      94% of study attempts. Acceptable or excellent image quality was achieved in more
      than 97% of attempts. Time away from the neonatal intensive care unit
      significantly decreased with this approach, with the mean duration of time away
      decreasing from 60 to 48 minutes (P < .0001). Obtaining MRI studies without
      sedation can be successfully implemented in a neonatal intensive care unit,
      nearly eliminating patient risks associated with sedation while improving
      utilization of hospital resources and maintaining adequate quality imaging.

PMID- 20697245
TI  - Observational study of treatment space in individual neonatal cot spaces.
AB  - PURPOSE: Technology developments in neonatal intensive care units have increased
      the spatial requirements for clinical activities. Because the effectiveness of
      healthcare delivery is determined in part by the design of the physical
      environment and the spatial organization of work, it is appropriate to apply an
      evidence-based approach to architectural design. This study aimed to provide
      empirical evidence of the spatial requirements for an individual cot or incubator
      space. SUBJECTS AND METHODS: Observational data from 2 simulation exercises were
      combined with an expert review to produce a final recommendation. A validated 5
      step protocol was used to collect data. Step 1 defined the clinical specialty and
      space. In step 2, data were collected with 28 staff members and 15 neonates to
      produce a simulation scenario representing the frequent and safety-critical
      activities. In step 3, 21 staff members participated in functional space
      experiments to determine the average spatial requirements. Step 4 incorporated
      additional data (eg, storage and circulation) to produce a spatial
      recommendation. Finally, the recommendation was reviewed in step 5 by a national
      expert clinical panel to consider alternative layouts and technology. RESULTS AND
      CONCLUSIONS: The average space requirement for an individual neonatal intensive
      care unit cot (incubator) space was 13.5 m2 (or 145.3 ft2). The circulation and
      storage space requirements added in step 4 increased this to 18.46 m2 (or 198.7
      ft2). The expert panel reviewed the recommendation and agreed that the average
      individual cot space (13.5 m2/[or 145.3 ft2]) would accommodate variance in
      working practices. Care needs to be taken when extrapolating this recommendation
      to multiple cot areas to maintain the minimum spatial requirement.

PMID- 20697246
TI  - The efficacy of mechanical vibration analgesia for relief of heel stick pain in
      neonates: a novel approach.
AB  - BACKGROUND: Hospitalized infants are often exposed to many painful procedures as
      a result of their illness or disease process. Untreated or poorly treated pain
      can have deleterious effects on normal nociceptive pain development as well as
      future development of pain pathways. Mechanical vibration has been found to be
      efficacious in adult and pediatric populations for the relief of mild-to-moderate
      acute and chronic pain. However, little is known about the efficacy of this
      intervention in the neonatal population. AIM: The purpose of this study was to
      test the hypothesis that mechanical vibration would be efficacious in the relief
      of pain associated with heel sticks in neonates. Heel sticks are one of the most
      common painful procedures during neonatal hospitalization. STUDY DESIGN: A random
      sequencing crossover design was used with infants acting as their own controls.
      SUBJECTS: Newborn infants of 35 weeks' gestation or greater (N = 20) met the
      inclusion criteria for the study. OUTCOME MEASURES: Pain during heel stick was
      measured with the Neonatal Infant Pain Scale. The Neonatal Infant Pain Scale is a
      nonintrusive tool with extensive evidence of its reliability and validity in the
      neonatal population, when used by trained observers. RESULTS: Mechanical
      vibration produced an analgesic effect for infants who had previously experienced
      painful heel sticks that approached statistical significance. CONCLUSIONS: The
      apparent limitations of mechanical vibration as analgesia may be due to the
      concurrent use of sucrose and pacifier, the effects of order (ie, habituation),
      or type II error. Because vibration produced the predicted positive effect in
      some circumstances, further investigation in larger samples within a randomized
      clinical trial is warranted.

PMID- 20697247
TI  - A cup of tea.

PMID- 20697248
TI  - Immunoarchitectural patterns in follicular lymphoma: efficacy of HGAL and LMO2 in
      the detection of the interfollicular and diffuse components.
AB  - Follicular lymphoma (FL) can exhibit variant histologic patterns that can lead to
      confusion with other B-cell lymphomas and reactive conditions. Diagnostic markers
      such as CD10 and BCL2 may be difficult to interpret in variant FL patterns, and
      are often diminished or absent in the interfollicular and diffuse components. We
      evaluated 2 recently characterized germinal center B-cell markers, human germinal
      center associated lymphoma (HGAL), and LIM-only transcription factor 2 (LMO2), in
      127 FL patient biopsies (94 nodal, 33 extranodal), and correlated the findings
      with histologic pattern, cellular composition, grade, and additional immunostains
      (CD20, CD3, CD21, CD10, BCL2, and BCL6). Architectural patterns included
      predominantly follicular (75%) and follicular and diffuse components (25%); 10
      cases showed marginal zone differentiation and 3 were floral variants. Eighty
      nine cases were low grade (38 grade 1; 51 grade 2) and 38 were grade 3 (29 grade
      3A and 9 grade 3B). HGAL had the highest overall sensitivity of detecting FL and
      was superior in detecting the interfollicular and diffuse components compared
      with BCL2, LMO2, CD10, and BCL6. All 28 cases that lacked CD10, expressed HGAL,
      and the majority also expressed LMO2. Our results show that HGAL and LMO2 are
      sensitive markers for FL diagnosis. The addition of HGAL and LMO2 to the
      immunohistologic panel is beneficial in the work-up of nodal and extranodal B
      cell lymphomas and the efficacy of HGAL in detecting the follicular,
      interfollicular and diffuse components of FL is of particular value in the
      setting of variant immunoarchitectural patterns.

PMID- 20697249
TI  - Epithelioid angiosarcoma of the skin: a study of 18 cases with emphasis on its
      clinicopathologic spectrum and unusual morphologic features.
AB  - We report 18 cases of cutaneous angiosarcoma with predominant or exclusive
      epithelioid morphology. Both sexes were similarly affected. Patients' ages ranged
      from 2 to 97 years, median 77.5 years; 2 were pediatric patients. In elderly
      patients scalp or facial lesions and cutaneous lesions arising within irradiated
      breast skin predominated. Limb lesions were seen in younger patients.
      Microscopically, the tumors were composed of packed polygonal cells with focal
      evidence of endothelial differentiation. Diverging phenotypes included syncytial
      growth of large cells with clear nuclei and prominent nucleoli, micronodules of
      tumor cells scattered in dermis, predominance of discohesive plasmacytoid
      polygonal cells with abundant bright eosinophilic cytoplasm, sheets of clear
      cells with coarse granular cytoplasm, trabecular and cord arrangement of tumor
      cells splaying the dermal collagen, or a pseudoglandular appearance owing to
      clear cell tubular arrangement with open lumina. These cases posed further
      diagnostic challenges simulating lymphoma, melanoma, lymphoepithelioma-like
      carcinoma, adnexal carcinoma, and neuroendocrine carcinoma. Immunohistochemical
      studies showed positivity for CD31 and CD34; no immunoreactivity was documented
      for other tested antigens including cytokeratins, S100 protein, melanocytic
      antigens, leukocyte common antigen, and desmin. Therapeutic modalities included
      combined local excision, chemotherapy, and radiotherapy, depending on patient
      clinical status. Of the 9 patients available for follow-up, 5 were alive and
      apparently well, 2 had recurrent disease, and 2 had died of tumor. Our data show
      that epithelioid cutaneous angiosarcoma may have a broad morphological spectrum,
      raising interpretive challenges on microscopy. In addition, its clinical
      presentation seems to differ in nonelderly patients, with lesions likely related
      to lymphedema or vascular malformations.

PMID- 20697250
TI  - Initial experience with a novel pre-sign-out quality assurance tool for review of
      random surgical pathology diagnoses in a subspecialty-based university practice.
AB  - We recently implemented a novel pre-sign-out quality assurance tool in our
      subspecialty-based surgical pathology practice at the University of Pittsburgh
      Medical Center. It randomly selects an adjustable percentage of cases for review
      by a second pathologist at the time the originating pathologist's electronic
      signature is entered and requires that the review be completed within 24 hours,
      before release of the final report. The tool replaced a retrospective audit
      system and it has been in successful use since January 2009. We report our
      initial experience for the first 14 months of its service. During this time, the
      disagreement numbers and levels were similar to those identified using the
      retrospective system, case turnaround time was not significantly affected, and
      the number of case amendments generated decreased. The tool is a useful quality
      assurance instrument and its prospective nature allows for the potential
      prevention of some serious errors.

PMID- 20697251
TI  - Immunohistochemical patterns of ProEx C in vulvar squamous lesions: detection of
      overexpression of MCM2 and TOP2A.
AB  - Two major subtypes of vulvar squamous cell carcinomas (SCC) have been described.
      Basaloid and warty SCC are human papillomavirus-related and associated with
      classic vulvar intraepithelial neoplasia (VIN). Keratinizing SCC is associated
      with lichen sclerosus and differentiated VIN, but not with human papillomavirus.
      This study was undertaken to examine the expression patterns of ProEx C in vulvar
      SCC and its precursors. We analyzed 22 cases with normal vulvar epidermis, 13
      cases of lichen sclerosus, 14 cases of condylomas, 23 cases of high-grade classic
      VIN, 6 cases of differentiated VIN, 3 cases of verrucous carcinomas, 10 cases of
      keratinizing SCC, and 8 cases of basaloid and warty SCC. ProEx C targets
      minichromosome maintenance protein and topoisomerase II alpha protein which are
      overexpressed in the cell nucleus during aberrant S-phase induction. Marked
      confluent ProEx C expression is present in high-grade classic VIN with nuclear
      staining extending into the middle and upper layers of the epidermis. Condylomas
      show parabasal nuclear immunoreactivity associated with scattered ProEx C
      positive nuclei in the more differentiated suprabasilar layers. Invasive SCC
      shows variable staining patterns. In contrast, ProEx C staining is essentially
      limited to the basal and parabasal layers in normal epidermis, lichen sclerosus,
      differentiated VIN, and verrucous carcinoma. Overall, ProEx C is a useful
      proliferation marker for high-grade VIN analogous to the staining patterns
      reported in high-grade cervical intraepithelial neoplasia.

PMID- 20697252
TI  - Clear cell change in colonic tubular adenoma and corresponding colonic clear cell
      adenocarcinoma is associated with an altered mucin core protein profile.
AB  - Clear cell change is seen in <1% of colonic tubular adenomas (TAs) and remains
      incompletely characterized. Associated adenocarcinomas can also demonstrate a
      clear cell phenotype. Eleven TAs with at least focal clear cell change with or
      without associated invasive adenocarcinoma, from 10 patients were studied. The
      lesions were stained with periodic acid-Schiff (PAS)/PAS-diastase and
      immunolabeled with antibodies to MUC2, MUC5AC, MUC6, CK7, CK20, and CDX2. Eight
      of 11 (77%) TAs with clear cell change had focal to extensive high-grade
      dysplasia. Two were associated with invasive clear cell adenocarcinoma. The
      adenomas and adenocarcinomas ranged from 0.5 to 3.5 cm. PAS/PAS-diastase stains
      showed minimal PAS(+) material in the clear cells. On immunohistochemical
      studies, the clear cells had decreased MUC2 labeling compared with the
      surrounding conventional adenoma in 9 of 11 (88%) cases, including the 2 clear
      cell adenocarcinomas. In 3 of the 11 lesions, the background TA showed at least
      focal MUC5 immunoreactivity, their associated clear cell area had decreased MUC5
      labeling in all 3 cases. No immunoreactivity to MUC6 was observed in the
      background TAs and clear cells in all cases. Compared with background TA, both
      increased and decreased expression of CK7, CK20 (in quantity), and CDX2 (in
      intensity) were observed in the clear cells of TAs and adenocarcinomas. One of
      the clear cell adenocarcinomas was CK20, CK7, CDX2 and the other was CK20, CK7,
      CDX2-focal positive. Thus, although the clear cells have different MUC protein
      profiles than the background adenomatous epithelium, invasive clear cell
      adenocarcinomas retained the typical CK20(+)/CK7(-) profile of conventional
      adenocarcinomas. Our results indicate that clear cell adenocarcinomas can be
      primary to the colorectum with identifiable precursors. Awareness of them and
      their immunoprofile allows distinction from clear cell lesions from other sites.

PMID- 20697253
TI  - Chronic gastritis in the setting of autoimmune pancreatitis.
AB  - Autoimmune pancreatitis (AIP) is a recently recognized disease entity. In some
      patients, this disease is associated with other inflammatory diseases. In this
      study, we aimed to elucidate the pathologic characteristics of AIP-associated
      gastritis (AIP-G). We evaluated and compared the pathologic findings and
      immunohistochemical expressions of immunoglobulin G (IgG)4 and IgG in gastric
      biopsy specimens from 13 AIP-G patients with those from patients of 2 control
      groups. We divided the AIP-G patients who did not receive steroid therapy [AIP-G
      ST(-)] into the following 2 groups: without Helicobacter pylori (HP) infection
      [AIP-G-HP(-)] and with HP infection [AIP-G-HP(+)]. The control groups comprised
      19 patients who were diagnosed with chronic active gastritis associated with HP
      infection and 7 patients with nonsteroidal anti-inflammatory drug-induced
      gastritis. We classified the findings for the gastric mucosa into those for the
      upper and the lower lamina propria. The characteristic finding of AIP-G groups
      was diffusely lymphoplasmacytic infiltration in the lamina propria. The IgG4
      positive plasma cell/IgG-positive plasma cell ratios (IgG4/IgG ratios) in both
      the upper and lower lamina propria in the AIP-G-ST(-) groups were predominantly
      higher than the corresponding values in the other groups. In the AIP-G-ST(-)
      groups, the IgG4/IgG ratio in the lower lamina propria was predominantly higher
      than that in the upper lamina propria, irrespective of the HP status. In
      conclusion, diffuse lymphoplasmacytic infiltration in the lamina propria and
      increased IgG4/IgG ratio in the gastric mucosa (notably in the lower lamina
      propria) may be the characteristic findings of AIP-G.

PMID- 20697254
TI  - Well-differentiated liposarcoma with low-grade osteosarcomatous component: an
      underrecognized variant.
AB  - Mature bone formation in well-differentiated liposarcoma and dedifferentiated
      liposarcoma has been described as a reactive or "metaplastic" change in most
      reports, and its neoplastic nature has not been widely appreciated. We herein
      describe 9 cases of well-differentiated/dedifferentiated liposarcoma with
      distinct areas of fibroosseous tissue histologically indistinguishable from low
      grade osteosarcomas, that is, parosteal osteosarcoma or low-grade central
      osteosarcoma. The tumors affected middle-aged to elderly patients, and occurred
      in the retroperitoneum and deep soft tissue of the extremities without connection
      to the skeletal system. Grossly, all the tumors showed biphasic appearance with
      lipogenic and osteogenic area, the latter representing 5% to 50% of the total
      tumor volume. Histologically, the lipogenic component exhibited typical histology
      of well-differentiated liposarcoma, whereas the osteogenic area consisted of
      fibroosseous tissue with numerous mature neoplastic bone trabeculae largely
      lacking osteoblastic rimming, with intervening fascicles of spindle cell
      proliferation showing low nuclear grade. All samples were positive for MDM2
      and/or CDK4 on immunohistochemical analysis; the antibodies stained many
      osteocytes, indicating that the bone is neoplastic rather than reactive. Three
      cases showed high-grade osteosarcomatous transformation juxtaposed to the low
      grade osteosarcomatous component, reminiscent of the "dedifferentiation"
      phenomenon of skeletal low-grade osteosarcoma. Follow-up revealed local
      recurrence in 4 cases, but no distant metastases were documented. Recognition of
      this earlier underappreciated subtype of well-differentiated/dedifferentiated
      liposarcoma is important, because the fibroosseous component may seem so bland
      that it may be confused with benign metaplasia such as myositis ossificans, or
      conversely, the lipomatous component may be inconspicuous that it may be
      dismissed as normal fat, and such misinterpretation may potentially result in
      suboptimal treatment.

PMID- 20697255
TI  - Tumor thickness at the tumor-normal interface: a novel pathologic indicator of
      chemotherapy response in hepatic colorectal metastases.
AB  - BACKGROUND: Progress in the treatment of hepatic colorectal metastases (HCRM)
      demands pathologic indicators of therapy response. We observed that a majority of
      residual tumor cells are seen at the tumor-normal interface (TNI) in resected
      HCRM specimens and hypothesized that tumor thickness at the TNI correlates with
      radiologic and pathologic response and recurrence-free survival (RFS). DESIGN:
      This study included 103 patients with HCRM resected after preoperative
      chemotherapy with or without bevacizumab. Imaging response was assessed by
      response evaluation criteria in solid tumors (RECIST) and recently described CT
      morphology criteria by Chun et al. The pathologic response was categorized as
      complete (no tumor cells), major (<50% residual tumor cells), or minor (> or =50%
      residual tumor cells). The maximum thickness of uninterrupted layers of tumor
      cells was measured perpendicular to the TNI by 2 pathologists independently,
      followed by consensus review for discrepant cases. For specimens containing >1
      tumor, the average tumor thickness at the TNI was used. RESULTS: Sixty-five
      patients received oxaliplatin-based chemotherapy, 38 received irinotecan-based
      chemotherapy, and 75 received concurrent bevacizumab. A complete pathologic
      response was seen in 9 patients, a major response in 44, and a minor response in
      50. Median tumor thickness at the TNI was 2.8 mm (interquartile range, 0.5 to 6
      mm). Tumor thickness correlated better with radiologic response as determined by
      Chun et al (P<0.0001) than by RECIST criteria (Spearman r=0.35, P<0.001). Tumor
      thickness correlated with pathologic response (Spearman r=0.80, P<0.0001).
      Greater thickness predicted shorter recurrence-free survival, and this
      correlation remained in multivariate analysis (P=0.015). Tumor thickness was
      smaller in patients treated with bevacizumab than in patients not given
      bevacizumab (P=0.03). CONCLUSIONS: Tumor thickness measured at the TNI is
      potentially a new prognostic factor for therapy response and survival outcome in
      patients with resected HCRM.

PMID- 20697256
TI  - Pediatric vaccines on the horizon.
AB  - Vaccines have saved the lives of millions of children and continue to be
      essential interventions to control infectious diseases among people of all ages.
      The list of recommended vaccines for children has expanded in recent years;
      however, many viral, bacterial and parasitic infections remain a major cause of
      morbidity and mortality in children. Improved vaccines to prevent Streptococcus
      pneumoniae and Neisseria meningitidis infections in children will soon be
      available. Recent scientific advances are being applied to design new childhood
      vaccines affording enhanced efficacy, safety and tolerability. Financial barriers
      and other obstacles to adequate vaccine access need to be eliminated to assure
      coverage for all children and adolescents.

PMID- 20697257
TI  - Clostridium difficile infection.
AB  - Clostridium difficile is the leading cause of hospital-acquired diarrhea in
      Europe and North America and is a serious reemerging pathogen. Recent outbreaks
      have led to increasing morbidity and mortality and have been associated with a
      new strain (BI/NAP1/027) of C difficile that produces more toxin than historic
      strains. With the increasing incidence of C difficile infection, clinicians have
      also seen a change in the epidemiology with increased infections in previously
      low-risk populations. This chapter highlights the current knowledge on C
      difficile virulence, human disease, epidemic outbreaks and optimal treatment
      strategies.

PMID- 20697259
TI  - Tickborne infections in the southern United States.
AB  - Established and emerging tickborne infections are significant causes of human
      illness in the southern United States. Rocky Mountain spotted fever, human
      monocytic ehrlichiosis, human ewingii ehrlichiosis and tularemia are known
      pathogens in this geographic distribution. Rickettsia parkeri and novel
      ehrlichioses are more recently described tickborne infections reviewed in this
      article. An understanding of the tick vectors, pathogenesis, epidemiology,
      clinical presentation, diagnosis and treatment is useful for the clinician
      treating patients potentially infected with any of these pathogens. Prevention
      measures, the optimal method for removing an attached tick and current and future
      vaccine development conclude this review.

PMID- 20697260
TI  - Emerging pathogens and knowledge in infectious diseases.

PMID- 20697258
TI  - Progress in the development of effective vaccines to prevent selected gram
      positive bacterial infections.
AB  - Infections caused by virulent Gram-positive bacteria, such as Staphylococcus
      aureus, group B streptococci and group A streptococci, remain significant causes
      of morbidity and mortality despite progress in antimicrobial therapy. Despite
      significant advances in the understanding of the pathogenesis of infection caused
      by these organisms, there are only limited strategies to prevent infection. In
      this article, we review efforts to develop safe and effective vaccines that would
      prevent infections caused by these 3 pathogens.

PMID- 20697261
TI  - Emerging zoonoses in the southern United States: toxocariasis, bovine
      tuberculosis and southern tick-associated rash illness.
AB  - The majority of emerging diseases in humans have been linked to zoonotic
      pathogens originating in domestic animals or wildlife. This is a public health
      concern because zoonotic infections affect several aspects of the society. The
      complex interactions among pathogen, host and environment also pose challenges in
      estimating the true burden of those infections. However, the recent development
      of new molecular diagnostic tools has allowed for better diagnosis of zoonotic
      infections. This review focuses on 3 emerging zoonoses, namely toxocariasis,
      bovine tuberculosis and southern tick-associated rash illness, and demonstrates
      that these infections may be more prevalent in the southern United States than
      previously recognized. This review places special emphasis on the recent
      epidemiologic trends, intra/interspecies transmission and clinical features of
      each of these zoonoses. In addition, treatment and prevention for each zoonotic
      pathogen are discussed. Clinicians working in the southern United States should
      be aware of the presence of those zoonotic infections.

PMID- 20697262
TI  - The benefits of transmission dynamics models in understanding emerging infectious
      diseases.
AB  - Factors associated with the emergence and transmission of infectious diseases
      often do not follow the assumptions of traditional statistical models such as
      linearity and independence of outcomes. Transmission dynamics models are well
      suited to address infectious disease scenarios that do not conform to these
      assumptions. For example, these models easily account for changes in the
      incidence rates of infection as the proportions of susceptible and infectious
      persons change in the population. Fundamental concepts relating to these methods,
      such as the basic reproductive number, the effective reproductive number and the
      susceptible-infected-recovered compartmental models, are reviewed. In addition,
      comparisons and contrasts are made between the following concepts: microparasites
      and macroparasites, deterministic and stochastic models, difference and
      differential equations and homogeneous and heterogeneous mixing patterns.
      Finally, examples of how transmission dynamics models are being applied to
      factors associated with emerging infectious diseases, such as zoonotic origins,
      microbial adaption and change, human susceptibility and climate change, are
      reviewed.

PMID- 20697263
TI  - 2009 H1N1 influenza: a twenty-first century pandemic with roots in the early
      twentieth century.
AB  - A swine-origin H1N1 triple-reassortant influenza A virus found to be a distant
      relative of the 1918 "Spanish flu" virus emerged in April 2009 to give rise to
      the first influenza pandemic of the 21st century. Although disease was generally
      mild and similar to seasonal influenza, severe manifestations including
      respiratory failure were noted in some, particularly those with underlying
      conditions such as asthma, pregnancy and immunosuppression. Children and younger
      adults accounted for most cases, hospitalizations and deaths. A reverse
      transcriptase-polymerase chain reaction assay was superior to antigen-based rapid
      tests for diagnosis. All 2009 H1N1 pandemic influenza strains were susceptible to
      1 or more neuraminidase inhibitors. Monovalent, unadjuvanted 2009 H1N1 vaccines
      were licensed in the United States in September 2009 and initially targeted to
      younger individuals, pregnant women, caretakers of infants and healthcare
      providers. The 2009 H1N1 pandemic highlights the need for modernization of
      influenza vaccines, improved diagnostics and more rigorous evaluation of
      mitigation strategies.

PMID- 20697264
TI  - Podoplanin immunostaining in cutaneous apocrine carcinoma and in cutaneous
      metastasis from the breast.

PMID- 20697265
TI  - Epithelial-to-mesenchymal transition in metaplastic breast carcinomas with
      chondroid differentiation: expression of the E-cadherin repressor Snail.
AB  - Epithelial-to-mesenchymal transition (EMT) is a key process in tumor progression
      and is induced by the master regulator Snail, a transcription factor that down
      regulates epithelial genes, including E-cadherin, and up-regulates mesenchymal
      genes. Metaplastic breast carcinomas with chondroid differentiation (MBCD) have
      an epithelial and a mesenchymal chondroid component, giving them morphologic
      features reminiscent of EMT. To determine whether EMT plays a role in MBCD, we
      differentially analyzed Snail and E-cadherin expression in 12 tumors by
      immunohistochemistry. The interface between the tumor components showed a
      transition from inactive cytoplasmic Snail expression in the carcinoma component
      to active nuclear Snail expression in the metaplastic cells. Membranous E
      cadherin staining was present in the epithelial and absent in the metaplastic
      component, showing a gradual loss of expression at the interface. E-cadherin
      expression was inversely correlated with active nuclear Snail expression. Our
      results suggest that EMT is induced in MBCD and may contribute to their frequent
      hematogenous metastasis.

PMID- 20697266
TI  - Characterization of a new monoclonal antibody against PAX5/BASP in 1525 paraffin
      embedded human and animal tissue samples.
AB  - INTRODUCTION: We describe the newly generated DAK-PAX5 monoclonal antibody raised
      against a fixation-resistant epitope of the human PAX5/BSAP molecule. MATERIALS
      AND METHODS: Following Western-blot, absorption, and chess-board titration tests,
      and optimization of antigen-retrieval and detection methods, DAK-Pax5 was used in
      parallel with a reference antibody (clone 24) on tissue micro-arrays (TMAs)
      constructed from normal human and animal tissues and from hematologic and
      nonhematologic human malignancies. Such TMAs were also tested with an anti-PAX2
      antibody. RESULTS: DAK-Pax5 reacted with normal human and animal B-cells and with
      460/473 B-cell non-Hodgkin lymphomas (B-NHLs). All plasmacytomas/plasmablastic
      tumors (n=13) and T/NK-cell neoplasms (n=264) turned out consistently negative as
      did acute myelogenous leukaemias (n=19) except 2 carrying t(8;21). Positivity was
      found in 6/6 and 155/169 lymphocyte predominant and classical HLs, respectively,
      although the staining intensity varied through cases. Among 521 nonhematologic
      malignancies, DAK-Pax5 reacted with 22/399 carcinomas (4/11 neuroendocrine, 2/4
      Merkel-cell, 4/21 prostatic, 1/11 urothelial, 1/26 renal, 2/12 cervical squamous
      cell, 3/13 ovarian, and 5/75 colonic). When compared with clone 24, DAK-Pax5
      produced a stronger positivity in most if not all B-NHLs and HLs. No cross
      reactivity with the anti-PAX2 antibody was recorded. DISCUSSION: DAK-Pax5
      represents a new reliable tool for diagnostics and research.

PMID- 20697267
TI  - Effects of a 6-week walking program on Taiwanese women newly diagnosed with early
      stage breast cancer.
AB  - BACKGROUND: In Western culture, evidence has shown that in women with breast
      cancer exercise decreases fatigue and improves quality of life. However, only 1
      pilot study about the effect of exercise has been examined in the Asian breast
      cancer population that indicated feasibility. Therefore, it is important to
      further study the effect of an exercise program for Taiwanese women with breast
      cancer. OBJECTIVE: The purpose of this study was to test the effects of a walking
      program on Taiwanese women newly diagnosed with early-stage breast cancer.
      METHODS: This was an experimental, longitudinal study with 4-time repeated
      measures based on Bandura's Self-efficacy Theory, with the aim of implementing
      interventions to boost exercise self-efficacy and to evaluate research outcomes.
      SPSS 17.0 with descriptive statistics using frequency, percentage, mean, and SD
      as well as inferential statistics such as t test, chi test, hierarchical linear
      model, repeated-measures analysis of variance, and analysis of covariance was
      used for data analysis. RESULTS: Results of this study indicated that subjects in
      the exercise group had significantly better quality of life, less fatigue, less
      sleep disturbances, higher exercise self-efficacy, more exercise behavior, and
      better exercise capacity compared with those in the usual-care group after the
      intervention. CONCLUSIONS: This program was effective and feasible, but more
      research studies with experimental, longitudinal design to verify the effects of
      this exercise program on Taiwanese women with breast cancer will be needed.
      IMPLICATIONS FOR PRACTICE: Nurses, depending on skill and knowledge, can
      encourage physical activity, refer patients to rehabilitation programs, and
      prescribe and monitor exercise in breast cancer population.

PMID- 20697268
TI  - How sexual history and knowledge of cervical cancer and screening influence
      Chinese women's screening behavior in mainland China.
AB  - BACKGROUND: Accurate information and knowledge about cervical cancer and
      screening importantly influence women's cervical screening participation. Sexual
      behavior plays a crucial role in human papillomavirus transmission and the
      subsequent development of cervical cancer. Indeed, the uptake of cervical
      screening among Chinese women is relatively low compared with other populations.
      OBJECTIVE: To understand women's attendance pattern of cervical screening,
      knowledge about cervical cancer and screening, and factors influencing their
      utilization of cervical screening in mainland China. METHODS: A cross-sectional
      survey was conducted to collect women's participation pattern for cervical
      screening, knowledge about cervical cancer and screening, sociodemographic
      information and sexual history, and barriers to participating in cervical
      screening. RESULTS: Married women and women who had had their first intercourse
      after the age of 21 years were significantly more likely to participate in
      screening. Screened women demonstrated a higher level of knowledge about the
      cervical screening procedure compared with nonscreened women (P = .002). Also,
      the scores of individual items such as women's knowledge of cervical screening
      and risk factors were significantly different between the 2 groups. CONCLUSION:
      The current system of free physical examinations for women in mainland China is a
      major motivator for women's utilization of cervical screening services. Chinese
      women's marital status and sexual history influence their screening behavior.
      IMPLICATIONS FOR PRACTICE: Unmarried women who have ever had sex should be
      encouraged to have cervical screening, and consistent and appropriate information
      about the preventive nature of cervical screening and risk factors associated
      with cervical cancer should be provided to the general public.

PMID- 20697269
TI  - Young breast cancer survivors: their perspectives on treatment decisions and
      fertility concerns.
AB  - BACKGROUND: Younger women diagnosed with breast cancer are more likely to have
      survival concerns related to fertility, which may influence their treatment
      decisions. OBJECTIVE: This qualitative study explores how young women make cancer
      treatment decisions and the role of fertility concerns in that process. METHODS:
      We used purposeful sampling to identify a diverse group of 20 young breast cancer
      survivors, half of whom had a child after breast cancer. We conducted open-ended
      telephone interviews and used cross-case, inductive analysis to identify themes.
      RESULTS: The main themes were (1) "I was young, I wanted to do everything
      possible to move forward with my life and not to have the cancer come back"; (2)
      "Fertility concerns are different for every woman"; (3) "My oncologist was
      great... a huge part of my survivorship"; and (4) "They didn't tell me about my
      options, and I didn't think about fertility until it was too late." CONCLUSIONS:
      Although fertility was important to many participants, treatment decisions were
      mainly motivated by survival concerns. Fertility concerns depended on life
      circumstances, and the timing in relation to diagnosis varied. There is a need
      for improved information regarding the impact of treatment on fertility and
      fertility preservation options, even if concerns are not expressed at diagnosis.
      IMPLICATIONS FOR PRACTICE: It is critical that cancer care providers provide
      timely information regarding fertility. Oncology nurses are particularly well
      positioned to serve this role by communicating with patients about their
      fertility concerns and reproductive planning prior to treatment and throughout
      the course of survivorship.

PMID- 20697270
TI  - Symptom distress and self-care strategies of colorectal cancer patients with
      diarrhea up to 3 months after surgery.
AB  - BACKGROUND: Diarrhea is common after colorectal surgery, but its severity and
      self-care methods have not been examined in depth. OBJECTIVE: To understand
      changes in and factors influencing diarrhea distress and self-care strategies of
      patients 1 week and 1, 2, and 3 months after colorectal cancer surgery. METHODS:
      For this descriptive, longitudinal study, 35 cancer patients were recruited from
      a teaching hospital in northern Taiwan. Data were collected in structured, one-on
      one interviews at 1 week and 1, 2, and 3 months after surgery. Variance and
      effects of diarrhea distress and number of self-care strategies were analyzed by
      repeated-measures analysis of variance and generalized estimating equation.
      Effectiveness scores for self-care strategies were analyzed by Wilcoxon signed
      rank test. RESULTS: Participants' overall level of diarrhea symptom distress was
      low. Distress level was highest 1 week after surgery, but gradually decreased
      thereafter. Over time after surgery, patients' frequency of using self-care
      strategies did not differ, but self-care strategies changed. Dietary modification
      and exercise were rated as the most effective strategies. Self-care information
      for hospitalized patients was primarily provided by medical personnel. The major
      factor affecting diarrhea distress was defecation frequency, and the major
      factors affecting self-care strategies were age, cancer stage, defecation
      frequency, and diarrhea distress. CONCLUSION: Diarrhea distress level gradually
      decreased, and self-care strategies changed with time after colorectal cancer
      surgery. IMPLICATIONS FOR PRACTICE: Because health care personnel were the
      primary source of self-care information for hospitalized patients after
      colorectal cancer surgery, nurses should use these findings to provide supportive
      treatment and educate patients and their family members about the cause and
      severity of diarrhea. Such education should include treatment-induced adverse
      effects as the basis for treating diarrhea.

PMID- 20697271
TI  - Time course of corneal biomechanical parameters after phacoemulsification with
      intraocular lens implantation.
AB  - PURPOSE: To assess the time course of corneal biomechanical parameters after
      phacoemulsification with intraocular lens implantation. METHODS: We examined 54
      eyes of 33 consecutive patients undergoing cataract surgery. We quantitatively
      assessed the values of corneal biomechanics characterized by corneal hysteresis
      (CH) and corneal resistance factor (CRF) using an Ocular Response Analyzer before
      and 1 day, 1 week, 1 month, and 3 months after surgery. We also investigated the
      relationship between these biomechanical parameters and central corneal thickness
      3 months after surgery. RESULTS: The CH was 9.7 +/- 1.1 (mean +/- SD) mm Hg
      preoperatively, and 9.0 +/- 1.4, 9.7 +/- 1.1, 9.7 +/- 1.1, and 9.7 +/- 1.3 mm Hg
      1 day, 1 week, 1 month, and 3 months postoperatively, respectively. The CRF was
      9.5 +/- 1.1 mm Hg preoperatively, and 8.8 +/- 1.2, 9.2 +/- 1.3, 9.1 +/- 0.9, and
      9.2 +/- 1.2 mm Hg 1 day, 1 week, 1 month, and 3 months postoperatively,
      respectively. Multiple comparisons demonstrated significant differences between
      measurements made before and 1 day after surgery (P = 0.01 for CH and CRF,
      Dunnett test). Both CH and CRF were significantly correlated with central corneal
      thickness (Pearson correlation coefficient r = 0.29; P = 0.03 for CH and r =
      0.42; P = 0.002 for CRF). CONCLUSIONS: Both CH and CRF decreased briefly at 1 day
      after cataract surgery but soon recovered to the preoperative levels, suggesting
      that cataract surgery does not induce a significant change in corneal
      biomechanics, except for 1 day postoperatively. The corneal thickness may play
      some role in corneal biomechanics even in postcataract eyes.

PMID- 20697272
TI  - Visual acuity and refraction after deep anterior lamellar keratoplasty with and
      without successful big-bubble formation.
AB  - PURPOSE: To compare visual acuity and refractive outcomes after Anwar's deep
      anterior lamellar keratoplasty (DALK) between eyes with and without successful
      big-bubble formation. MATERIALS AND METHODS: In this retrospective comparative
      study, keratoconic eyes undergoing DALK with the big-bubble technique were
      divided into 2 groups: group 1 in which a bared Descemet membrane (DM) was
      achieved and group 2 in which layer-by-layer manual dissection was performed
      because of the lack of big-bubble formation after several intrastromal air
      injections. The 2 groups were compared with respect to best spectacle-corrected
      visual acuity, keratometric astigmatism, and refractive error at months 1, 3, 6,
      and 12, and at least 3 months after complete suture removal. RESULTS: A total of
      123 keratoconic eyes were enrolled. A bared DM was successfully achieved in 100
      eyes (81.3%) (group 1), whereas in 23 eyes (18.7%) (group 2), some posterior
      stroma was left in place. The mean follow-up period was 21 +/- 9 months in group
      1 and 23 +/- 9 months in group 2 (P = 0.37). Postoperative best spectacle
      corrected visual acuity was significantly better in group 1 than in group 2 at
      months 1, 3, 6, and 12. But, at the final examinations, there was no significant
      difference between the study groups (0.24 +/- 0.21 logarithm of the minimum angle
      of resolution in group 1 and 0.32 +/- 0.14 logarithm of the minimum angle of
      resolution in group 2; P = 0.18). The 2 groups were comparable regarding
      keratometric astigmatism and spherical equivalent refractive error throughout the
      follow-up period. CONCLUSIONS: Retention of posterior corneal stroma delayed
      visual recovery after DALK using Anwar's technique, but the participants in this
      group ultimately reached the same levels of visual acuity as observed in the
      bared-DM group.

PMID- 20697273
TI  - Clinical trials of therapeutic ocular surface medium for moderate to severe dry
      eye.
AB  - PURPOSE: To investigate therapeutic ocular surface medium (TOSM), a potential
      physiological tear replacement therapy, for moderate to severe dry eye. METHODS:
      Forty-six patients with symptoms of moderate to severe dry eye despite maximal
      standard therapy were enrolled in a prospective pilot study of TOSM over 1 month
      (n = 10) and a randomized, double-masked, controlled trial of TOSM versus saline
      (placebo) over 2 months (n = 36). The primary outcome measure was conjunctival
      rose bengal staining. RESULTS: An improvement in conjunctival rose bengal
      staining by >=3 points occurred in 7 of 10 patients receiving TOSM in the pilot
      study (P = 0.017) and in 8 of 18 patients (44%) in the randomized trial (P =
      0.982). In the pilot study, subjective dry eye symptoms significantly improved (P
      = 0.005). TOSM significantly improved the blepharitis score (P = 0.002) and
      conjunctival impression cytology (P = 0.028) in the randomized controlled trial.
      There were no serious or irreversible side effects with TOSM. CONCLUSIONS: TOSM
      is a physiological tear replacement for dry eye that, unlike autologous serum,
      can be easily manufactured, could be widely available, and may also be beneficial
      for blepharitis.

PMID- 20697275
TI  - Recurrence rate using fibrin glue-assisted ipsilateral conjunctival autograft in
      pterygium surgery: 2-year follow-up.
AB  - AIMS: To determine the recurrence rate after pterygium excision with ipsilateral
      conjunctival autograft using fibrin glue. METHODS: One hundred eleven eyes of 92
      patients operated for primary pterygium were retrospectively evaluated for
      recurrence rate and intraoperative and postoperative complications. Pterygia were
      preoperatively divided in atrophic/grade 1 (n = 2; 1.80%), intermediate/grade 2
      (n = 85; 76.58%), or fleshy/grade 3 (n = 24; 21.62%) types. All patients were
      operated using an ipsilateral conjunctival autograft fixed with fibrin glue. Only
      patients with 2-year follow-up were included in this study. RESULTS: Two years
      after surgery, the mean recurrence rate was 4.50% (n = 5). No intraoperative
      complications were noted. Postsurgical complications were graft pseudoedema (n =
      45; 40.54%), graft retraction (n = 3; 2.70%), and donor site granuloma (n = 1;
      0.90%). CONCLUSION: Fibrin glue-assisted ipsilateral conjunctival autograft seems
      to be safe and efficacious and associated with a low rate of recurrence.

PMID- 20697276
TI  - Comparison of the effects of fourth-generation fluoroquinolones on epithelial
      healing after photorefractive keratectomy.
AB  - PURPOSE: To compare the effects of fluoroquinolones gatifloxacin and moxifloxacin
      used for antimicrobial prophylaxis after photorefractive keratectomy (PRK) on
      epithelial healing. METHODS: Forty-four patients randomly received the
      prophylactic antibiotics gatifloxacin (Gatiflo; 0.3% gatifloxacin ophthalmic
      solution, Handok, Chungbuk, Korea, no preservative) in 1 eye and moxifloxacin
      (Vigamox; 0.5% moxifloxacin hydrochloride ophthalmic solution, Alcon
      Laboratories, Inc, Fort Worth, TX, no preservative) in the fellow eye after PRK.
      Corneal epithelium was circumferentially removed along a 7-mm zone mark. After
      PRK, all patients used topical antibiotics 4 times a day until the epithelium
      healed completely. Starting from postoperative day 1, epithelial healing times
      and defect sizes were recorded by slit-lamp examination and anterior segment
      photography. Postoperative pain and discomfort induced by the eyedrops were
      recorded. Additionally, therapeutic contact lenses were cultured to assess the
      antibacterial efficacy of fluoroquinolones. RESULTS: The mean epithelial healing
      times after PRK were similar for the 2 groups: 2.97 +/- 0.41 days for
      gatifloxacin and 2.95 +/- 0.48 days for moxifloxacin (P = 0.81). There was no
      statistically significant difference in mean defect size on each postoperative
      day between the treatment groups. There was no difference in postoperative pain
      and discomfort. No statistically significant differences were observed between
      eyes treated with gatifloxacin and moxifloxacin in terms of uncorrected visual
      acuity or best-corrected visual acuity at 3 months postoperatively. CONCLUSION:
      No significant differences were found in the effects of the preservative-free
      fourth-generation fluoroquinolones gatifloxacin and moxifloxacin on epithelial
      healing after PRK.

PMID- 20697277
TI  - Pigmented apocrine hidrocystoma of the caruncle.
AB  - PURPOSE: To describe the clinical and immunopathologic features of the first
      convincing apocrine hidrocystoma of the caruncle that happened to be pigmented.
      METHODS: Case report with clinical evaluation, ultrasound biomicroscopy, and
      paraffin-embedded tissue stained with hematoxylin and eosin, periodic acid
      Schiff, and immunohistochemical markers. RESULTS: Ultrasound biomicroscopy
      identified a cyst occurring in a 56-year-old white woman. Histopathologically, it
      was lined by an inner eosinophilic columnar epithelium that was gross cystic
      disease fluid protein-15-positive and evinced apical decapitation secretion and
      periodic acid-Schiff-positive, diastase-resistant cytoplasmic granules. Fontana-
      and MART-1-positive melanin granules were demonstrated. There was an outer layer
      of smooth muscle actin-positive myoepithelial cells. An adjacent apocrine gland
      was discovered with identical staining characteristics but without melanin
      granules. CONCLUSIONS: Classical apocrine gland cysts can exceptionally develop
      in the caruncle. The light dispersion of cytoplasmic melanin found in the lining
      cells may have contributed to the cyst's clinical pigmentation, which is
      otherwise generally regarded as the result of the Tyndall effect, wherein blue
      wavelengths of light reflect from a colloidal solution of lipofuscin and cell
      debris.

PMID- 20697280
TI  - Scleral lenses and ocular cicatricial pemphigoid.

PMID- 20697279
TI  - Granular and lattice deposits in corneal dystrophy caused by R124C mutation of
      TGFBIp.
AB  - PURPOSE: Both granular and lattice deposits are present in Avellino corneal
      dystrophy (ACD), primarily associated with the R124H mutation of transforming
      growth factor-beta-induced (TGFBIp). We investigated the presence of these
      deposits in other TGFBI mutations and the use of Thioflavin-T (ThT), a
      fluorescent amyloid stain for characterizing corneal amyloid deposits. METHODS:
      Surgical corneal specimens of 3 unrelated patients clinically diagnosed with ACD
      were studied. Corneal sections from normal individuals and patients with prior
      lattice corneal dystrophy (LCD) were used as controls. Histochemical studies were
      performed with Congo red and Masson trichrome stains, and fluorescent imaging
      with scanning laser confocal microscopy was performed for ThT and anti-TGFBIp
      antibody staining. RESULTS: Clinical and histopathological findings supported the
      diagnoses of ACD in these 3 cases in whom granular deposits stained with Masson
      trichrome and lattice deposits stained with ThT and Congo red showed
      birefringence and dichroism as expected. However, genotyping revealed a
      heterozygous R124C mutation in each case. In addition to classical stromal
      deposits, unique subepithelial TGFBIp aggregates, which stain with neither ThT
      nor trichrome, were observed. In control LCD sections, stromal deposits were
      stained with ThT but not with trichrome, confirming lack of granular deposits.
      CONCLUSIONS: Our results demonstrate that both granular and lattice corneal
      deposits can be associated with R124C mutation in addition to the more common
      R124H mutation. An additional feature of nonhyaline, nonamyloid, TGFBIp
      subepithelial deposits might substantiate the categorization of such cases as a
      variant form of ACD. This study further validates ThT staining for detection of
      amyloid TGFBIp deposits.

PMID- 20697281
TI  - Epithelial responses to rubbing-related mechanical forces.
AB  - PURPOSE: To examine for epithelial thickness changes in response to compressive
      and shear forces associated with eye rubbing. METHODS: The Holden-Payor optical
      pachometer was used to measure total and stromal-endothelial thickness, at
      central (right eye) and midperipheral (left eye) locations, for 12 subjects with
      normal corneas. Epithelial thickness was determined by subtraction. Baseline
      measurements were compared with measurements recorded immediately after 15
      seconds of circular pattern rubbing over the cornea, using an index finger pad,
      and light to moderate force. Four subjects in each of 3 groups with mean ages of
      19.5, 45.3, and 70.2 years were assessed. Measurement continued at 15-minute
      intervals until baseline thickness was restored. RESULTS: An 18.4% reduction in
      epithelial thickness was recorded immediately after rubbing for central right eye
      and midperipheral left eye assessments. Both findings were statistically
      significant (P < 0.05). Recovery to baseline thickness occurred between 15 and 30
      minutes centrally and between 30 and 45 minutes midperipherally. CONCLUSION:
      These results indicate a statistically significant mechanical trauma to the
      epithelium after 15 seconds of light to moderate rubbing. With reference to the
      rheological properties of the cytoskeleton, an attempt to explain how the
      epithelium could lose and recover thickness has been made. Apart from cell
      flattening, displacement from the rubbed area of intercellular water, cytoplasm
      from ruptured cells, chains of wing cells, and mucin are suggested as possible
      thinning mechanisms. Extraneous eye rubbing may adversely alter the results
      obtained with pachymetry, videokeratography, wavefront aberrometry, refraction,
      and results obtained with orthokeratology contact lenses.

PMID- 20697282
TI  - Transient anterior corneal deposits in a human immunodeficiency virus-positive
      patient.
AB  - PURPOSE: To report findings of pigmented anterior corneal deposits in a human
      immunodeficiency virus-positive patient. METHODS: Case report. A 49-year-old
      human immunodeficiency virus-positive patient was examined after the appearance
      of pigmented corneal deposits. Slit-lamp biomicroscopy, fundus photography, and
      laser-scanning in vivo confocal microscopy were performed to visually document
      the ocular condition. RESULTS: The patient had a history of Mycobacterium avium
      infection and was suspected to have recovery uveitis from a cytomegalovirus
      infection. Small, rounded, light brown-colored deposits were distributed across
      the anterior cornea from limbus to limbus, bilaterally. In vivo confocal
      microscopy revealed the deposits to be confined to the basal epithelium and
      Bowman layer, whereas the posterior stroma, Descemet membrane, and the
      endothelium appeared normal. Systemic steroid treatment was administered, and 2
      weeks later, the deposits had vanished on slit-lamp examination, whereas remnants
      were observed at the microscopic level. CONCLUSIONS: The deposits were unusual
      for their anterior corneal location and pancorneal distribution. The response to
      systemic steroid treatment remains unexplained and illustrates the complexity of
      the underlying conditions, their treatment, and the associated pathways of ocular
      manifestation.

PMID- 20697283
TI  - Outcome of descemet stripping automated endothelial keratoplasty in patients with
      an anterior chamber intraocular lens.
AB  - PURPOSE: To evaluate the outcome of Descemet stripping automated endothelial
      keratoplasty (DSAEK) in patients with a retained anterior chamber intraocular
      lens (ACIOL). METHODS: A retrospective review of 11 patients with corneal
      decompensation and ACIOL who underwent DSAEK was performed. All patients except 1
      had open-loop style ACIOLs, and in all cases, there was adequate anterior chamber
      depth. At the time of surgery, 6 patients had a temporary suture to secure their
      graft, 2 of which were retained from the insertion method, and the other 4 were
      placed additionally. Postoperatively, the rate of donor detachment, graft
      clarity, corneal pachymetry, and visual acuity were noted. RESULTS: There was
      only 1 graft dislocation postoperatively, which was reattached successfully by
      air injection. There was 1 primary graft failure (without dislocation) among the
      11 patients during the mean follow-up of 12 months (range: 6-25 months); at last
      follow-up, the visual acuity had improved in all the other 10 patients.
      CONCLUSIONS: This series demonstrates that DSAEK can be performed successfully in
      patients with existing ACIOLs. These early outcomes suggest that DSAEK alone may
      be considered as an alternative to a lens exchange with DSAEK in patients with
      adequate anterior chamber depth.

PMID- 20697284
TI  - Secondary localized sectoral keratoconjunctival amyloidosis from ocular trauma.
AB  - PURPOSE: To report a case of unilateral localized sectoral conjunctival
      amyloidosis associated with corneal amyloidosis. METHODS: Case report. RESULTS: A
      27-year-old woman with a history of ocular trauma presented with a limbus-based
      pink-yellow colored superonasal conjunctival lesion with adjacent superonasal
      sectoral corneal lattice-like changes. The lesion was monitored for 3 years with
      minimal enlargement, but conjunctival chalasis developed, which was bothersome to
      the patient. A conjunctival excisional biopsy confirmed the diagnosis of
      amyloidosis. CONCLUSIONS: To our knowledge, this is the first report of
      unilateral combined corneal and conjunctival amyloid deposition. Even more
      unusual was the sectoral distribution of the amyloid. This likely represents a
      local production and deposition of amyloid.

PMID- 20697285
TI  - Secondary DMEK for poor visual outcome after DSEK: donor posterior stroma may
      limit visual acuity in endothelial keratoplasty.
AB  - PURPOSE: To describe the clinical outcome of a secondary Descemet membrane
      endothelial keratoplasty (DMEK) to manage poor visual outcome after Descemet
      stripping endothelial keratoplasty (DSEK). METHODS: Three eyes of 3 patients that
      underwent DSEK for Fuchs endothelial dystrophy showed fluctuating and/or poor
      visual outcome ranging from 20/80 (0.25) to 20/40 (0.5). In a secondary
      procedure, 16-22 months after the initial DSEK, the DSEK graft was removed and
      replaced by a DMEK graft. The clinical outcome was evaluated by comparing the pre
      to postoperative best-corrected visual acuity (BCVA), Pentacam imaging, and
      biomicroscopy. RESULTS: All secondary DMEK procedures were uneventful. Three
      months after secondary DMEK, all eyes had a BCVA of 20/25 (0.8) or better.
      Pentacam analysis showed a virtually stable anterior corneal curvature in all
      cases, but among cases, the transplant exchange induced variable refractive
      change at the posterior corneal surface. CONCLUSION: To manage DSEK cases with
      poor visual outcome, secondary DMEK may be a feasible procedure potentially
      resulting in full visual rehabilitation, as in primary DMEK. The presence of
      donor posterior stroma in DSEK, but not in DMEK grafts, may be a major factor in
      limiting the final BCVA in endothelial keratoplasty.

PMID- 20697286
TI  - Changes in corneal biomechanics in patients with keratoconus after penetrating
      keratoplasty.
AB  - PURPOSE: To examine the biomechanical properties of keratoconic eyes following
      penetrating keratoplasty and to compare results with the biomechanical
      characteristics of manifest keratoconus, forme fruste keratoconus and normal eyes
      as measured with the Reichert ocular response analyzer (ORA). METHODS: This
      retrospective analysis comprised a total of 169 eyes: 34 eyes with forme fruste
      keratoconus (group FF), 36 eyes with manifest keratoconus (Group KC), 36 eyes
      that have undergone penetrating keratoplasty (Group PK) and a control group of 63
      normal eyes (Group N). Corneal hysteresis (CH), corneal resistance factor (CRF),
      corneal compensated intraocular pressure, and Goldmann correlated intraocular
      pressure were measured by ORA. Central corneal thickness was calculated by the
      integrated handheld ultrasonic pachymeter of the ORA. The statistical analysis
      focused on CH and CRF changes among the 4 groups. RESULTS: When compared with
      normal eyes, mean CH and CRF values were found significantly lower in all groups
      (P < 0.05). Mean CH values were 8.19 +/- 1.49 mm Hg in Group KC, 9.21 +/- 1.38 mm
      Hg in Group FF, 10.16 +/- 1.93 mm Hg in Group PK, and 11.43 +/- 1.52 mm Hg in
      normal eyes (Group N). Although there was not a significant difference in mean CH
      values between Groups PK and FF (P = 0.072), the difference was significant
      between Groups KC as well as FF and Groups KC and PK (P < 0.05). Mean CRF values
      were found as 6.79 +/- 1.81 mm Hg (Group KC), 8.21 +/- 1.64 mm Hg (Group FF),
      9.94 +/- 2.34 mm Hg (Group PK), and 11.53 +/- 1.83 mm Hg in Group N. The
      difference was statistically significant among all groups (P < 0.05).
      CONCLUSIONS: Penetrating keratoplasty has a beneficial effect on corneal
      biomechanics in keratoconic eyes. CH and CRF parameters approach the range of
      normal eyes after corneal transplantation.

PMID- 20697287
TI  - Bacteroides spp. and diarrhea.
AB  - PURPOSE OF REVIEW: The purpose of this review is to describe recent progress in
      the understanding of the role of Bacteroides spp. in human diarrheal diseases and
      newer murine studies implicating certain Bacteroides spp. in colorectal cancer.
      RECENT FINDINGS: Bacteroides fragilis is the only strain of Bacteroides spp.
      associated with diarrheal disease. Toxin-producing strains of B. fragilis, termed
      enterotoxigenic Bacteroides fragilis (ETBF), are an established cause of
      diarrheal disease in people. The clinical syndrome associated with ETBF diarrheal
      disease encompasses abdominal pain, tenesmus and inflammatory diarrhea. Two new
      studies conducted in mice have further defined the chronic inflammatory response
      associated with ETBF infection and observed that in the multiple intestinal
      neoplasia mouse strain, heterozygotes for the adenomatous polyposis coli gene,
      ETBF infection enhances development of colonic tumors. Separate murine studies
      have begun to define the role of nontoxin-producing B. fragilis as a symbiont,
      serving possibly to protect the host from colonic inflammation. SUMMARY: B.
      fragilis remains the leading anaerobe in human disease. ETBF is emerging as an
      important cause of human diarrheal disease but additional epidemiologic studies
      are needed to better understand the role of ETBF human disease.

PMID- 20697288
TI  - Size of the direct-to-consumer genomic testing market.
AB  - There has been enormous interest in the recent development of consumer genomics
      services, but very little is known about their impact. Using publicly available
      information, we estimate that the market for genetic susceptibility tests for
      complex diseases is much smaller than previously suggested, and hence consider
      that regulation through restrictive statutory legislation may be excessive.

PMID- 20697289
TI  - Simplifying informed consent for biorepositories: stakeholder perspectives.
AB  - PURPOSE: Complex and sometimes controversial information must be conveyed during
      the consent process for participation in biorepositories, and studies suggest
      that consent documents in general are growing in length and complexity. As a
      first step toward creating a simplified biorepository consent form, we gathered
      data from multiple stakeholders about what information was most important for
      prospective participants to know when making a decision about taking part in a
      biorepository. METHODS: We recruited 52 research participants, 12 researchers,
      and 20 institutional review board representatives from Durham and Kannapolis, NC.
      These subjects were asked to read a model biorepository consent form and
      highlight sentences they deemed most important. RESULTS: On average,
      institutional review board representatives identified 72.3% of the sentences as
      important; researchers selected 53.0%, and participants 40.4% (P = 0.0004).
      Participants most often selected sentences about the kinds of individual research
      results that might be offered, privacy risks, and large-scale data sharing.
      Researchers highlighted sentences about the biorepository's purpose, privacy
      protections, costs, and participant access to individual results. Institutional
      review board representatives highlighted sentences about collection of basic
      personal information, medical record access, and duration of storage. CONCLUSION:
      The differing mandates of these three groups can translate into widely divergent
      opinions about what information is important and appropriate to include a consent
      form. These differences could frustrate efforts to move simplified forms--for
      biobanking as well as for other kinds of research--into actual use, despite
      continued calls for such forms.

PMID- 20697290
TI  - Evaluation of the intestinal colonization by microencapsulated probiotic bacteria
      in comparison with the same uncoated strains.
AB  - BACKGROUND: Beneficial findings concerning probiotics are increasing day by day.
      However, one of the most important parameter which affects the probiotic activity
      of a microorganism is its survival during the gastroduodenal transit. Some
      microencapsulation techniques could be applied to bacterial cells to improve this
      parameter. METHODS: A comparison between the intestinal colonization by
      microencapsulated bacteria and the same not microencapsulated strains has been
      conducted in a double blind, randomized, cross-over study. The study (April to
      July 2005) involved 44 healthy volunteers. In particular, participants were
      divided into 2 groups: group A (21 participants) received a mix of probiotic
      strains Lactobacillus plantarum LP01 (LMG P-21021) and Bifidobacterium breve BR03
      (DSM 16604) in an uncoated form, group B (23 participants) was given the same
      strains microencapsulated with a gastroresistant material. The not
      microencapsulated strains were administered at 5 x 10(9) colony forming
      units/strain/d for 21 days, whereas the microencapsulated bacteria were given at
      1 x 10(9) colony forming units/strain/d for 21 days. At the end of the first
      period of treatment with probiotics a 3 weeks washout phase has been included in
      the study protocol. At the end of the washout period the groups were crossed: in
      detail, group A had the microencapsulated and group B the uncoated bacteria. The
      administered amounts of each strain were the same as the first treatment. The
      quantitative evaluation of intestinal colonization by strains microencapsulated
      or not microencapsulated was made by fecal samples examination at the beginning
      of the clinical trial, after 10 and 21 days of each treatment period. In
      particular, fecal heterofermentative Lactobacilli and Bifidobacteria have been
      counted. RESULTS: A statistically significant increase in the fecal amounts of
      Lactobacilli and Bifidobacteria was recorded in both groups at the end of each
      treatment compared with d0 or d42 (P<0.0001 and P<0.0001 at d21, P<0.0001 and
      P<0.0001 at d63 for Lactobacilli and Bifidobacteria, respectively), confirming
      the ability of the 2 strains to colonize the human gut, either in a
      gastroprotected form or not. Participants treated with the microencapsulated
      bacteria reported a kinetics of intestinal colonization quite similar to
      participants who received not coated strains. CONCLUSIONS: Probiotics are able to
      exert many different beneficial effects on the human host. These effects are
      mediated by the number of viable cells which reach the gut. The
      microencapsulation technique used in this study is a valid strategy to
      significantly improve gastroresistance of strains, thus enhancing their probiotic
      activity and allowing the use of a 5 times lower amount.

PMID- 20697291
TI  - The use of probiotics in healthy volunteers with evacuation disorders and hard
      stools: a double-blind, randomized, placebo-controlled study.
AB  - BACKGROUND: Evacuation disorders and hard stools are common in industrialized
      countries, affecting on average 12% to 17% of the adult healthy population at any
      age. Dietary supplementation with probiotic microorganisms may be useful in
      reducing the disorder. METHODS: We performed a double-blind, randomized, placebo
      controlled study to evaluate the effectiveness of 2 different probiotic blends,
      either mixed Lactobacillus plantarum LP01 (LMG P-21021) and Bifidobacterium breve
      BR03 (DSM 16604) or Bifidobacterium animalis subspecies lactis BS01 (LMG P
      21384), in the management of evacuation disorders and intestinal discomfort. In a
      period of 5 years (2003 to 2008), the study involved 300 healthy volunteers (151
      males and 149 females; age 24 to 71 y) with evacuation disorders and hard stools.
      In particular, subjects were divided into 3 groups: 80 subjects in the group A
      received placebo, 110 subjects in the group B received mixed L. plantarum LP01
      and B. breve BR03 (2.5 x 10 colony-forming units/d of each strain), and 110
      subjects in the group C received B. animalis subsp. lactis BS01 (5 x 10 colony
      forming units/d) for 30 days. At the beginning of the observational study, the
      healthy status of volunteers was evaluated by a complete, laboratory and
      ultrasound study of the abdomen. The physical examination was repeated after 15
      and 30 days. In particular, the main troubles typically associated with
      evacuation disorders and hard stools as well as abdominal bloating were
      considered as parameters of interest. Exclusion criteria were items of
      gastrointestinal diseases and antibiotics intake. RESULTS: Subjects treated with
      the mixed probiotic strains L. plantarum LP01 and B. breve BR03 or B. animalis
      subsp. lactis BS01 reported a significant improvement in the number of weekly
      bowel movements and in the main troubles associated with evacuations,
      particularly consistency of feces and ease of expulsion. Discomfort items such as
      abdominal bloating and anal itching, burning, or pain also registered a relevant
      improvement in the active groups receiving probiotics. CONCLUSIONS: The intake of
      an effective amount of mixed L. plantarum LP01 and B. breve BR03 or B. animalis
      subsp. lactis BS01 for 30 days is able to significantly relieve the evacuation
      disorders and hard stools, thus providing a useful tool for the management of
      such condition, which is particularly widespread in industrialized countries at
      any age.

PMID- 20697292
TI  - Proton pump inhibitors and the risk of colorectal cancer: a meta-analysis.

PMID- 20697293
TI  - Papillary cancer of thyroid in celiac disease.
AB  - BACKGROUND: Celiac disease (CD) has been established as being associated with
      several thyroid diseases. However, occurrence of thyroid epithelial cancer in
      celiac patients has been rarely described. GOAL: We describe the prevalence of
      thyroid carcinoma detected in a cohort of Italian celiac patients, with the aim
      to carry out a prospective analysis of the risk of celiac patients to develop
      thyroid carcinoma. METHODS: The study population included all CD patients
      diagnosed at the Collaborating Centers of the Italian Registry of CD between
      January 1, 1982 and December 31, 2006. Upon diagnosis of CD and at every
      subsequent clinical control, the Collaborating Centers filled in a validated form
      for each CD patient reporting information about demographic data, possible
      occurrence of a thyroid disease, and adherence to a gluten-free diet. RESULTS: Of
      the 1757 celiac patients enrolled, 6 developed a papillary thyroid carcinoma
      during the follow-up period (mean: 18.1 y). The Standardized Incidence Ratio
      resulted 2.55 (95% confidence interval=0.93-5.55; P<0.01). The mean age of
      diagnosis of CD in patients who developed thyroid carcinoma was rather low (40 y)
      and not statistically different from that of those who did not develop thyroid
      carcinoma. The number of gluten-containing diet per month did not correlate with
      the development of a thyroid carcinoma. CONCLUSIONS: There is a 2.5-fold
      increased risk of papillary cancer of thyroid for celiac patients. A prompt
      diagnosis of CD and a strict adherence to gluten-free diet do not seem to protect
      from the development of this malignancy.

PMID- 20697294
TI  - Long-term use of angiotensin converting enzyme inhibitors is associated with
      decreased incidence of advanced adenomatous colon polyps.
AB  - BACKGROUND: The long-term use of angiotensin converting enzyme (ACE) inhibitors
      may reduce the risk of developing colorectal cancer (CRC). GOAL: The aim of our
      study was to determine how long-term use of lisinopril influences the development
      of advanced adenomatous polyps (APs). STUDY: We performed a retrospective study
      of patients who were found to have 1 or more histologically confirmed APs on an
      index colonoscopy, and who also had a follow-up colonoscopy 3 to 5 years later.
      APs found on the follow-up colonoscopy were evaluated for location, size, number,
      and advanced features. Patients were divided into 2 groups: (1) those who used
      lisinopril continuously during the interval between colonoscopies and (2) those
      who were lisinopril naive. Clinical factors were evaluated for their association
      with advanced APs in both the groups. RESULTS: A total of 4660 patients with a
      history of AP were identified. There were 1760 continuous lisinopril users and
      2900 nonusers. Univariate analysis showed that patients with lisinopril use had
      fewer right-side APs (odds ratio=0.68, P<0.001) and fewer total number of APs
      (P<0.001). Lisinopril users had a 41% reduced incidence of advanced APs compared
      with the nonusers (odds ratio=0.59, P<0.001). A Mann-Whitney U test revealed that
      among lisinopril users, patients with advanced APs were on a lower dose of the
      medication compared with patients without advanced APs (mean dose=17.2 mg vs.
      20.1 mg, respectively; P<0.001). Spearman correlation analyses indicated an
      inverse relationship between lisinopril dosage and number of polyps (P<0.001).
      There was also an inverse relationship between dosage and size of polyps
      (P<0.001); higher dosages of lisinopril were significantly associated with
      smaller size of polyps. The protective effect of lisinopril was significant even
      when adjusted for age, body mass index, aspirin/nonsteroidal anti-inflammatory
      drug use, and statin use. CONCLUSIONS: The use of lisinopril was associated with
      a 41% reduction in the incidence of advanced APs during a period of 3 to 5 years,
      even after adjustment for other known polyp risk factors. We speculate that long
      term ACE inhibitors use may reduce the development of CRCs by reducing the
      development of advanced APs.

PMID- 20697295
TI  - Genetic predictors of glucocorticoid response in pediatric patients with
      inflammatory bowel diseases.
AB  - BACKGROUND: Glucocorticoids (GCs) are used in moderate-to-severe inflammatory
      bowel diseases (IBD) but their effect is often unpredictable. AIM: To determine
      the influence of 4 polymorphisms in the GC receptor [nuclear receptor subfamily
      3, group C, member 1 (NR3C1)], interleukin-1beta (IL-1beta), and NACHT leucine
      rich-repeat protein 1 (NALP1) genes, on the clinical response to steroids in
      pediatric patients with IBD. METHODS: One hundred fifty-four young IBD patients
      treated with GCs for at least 30 days and with a minimum follow-up of 1 year were
      genotyped. The polymorphisms considered are the BclI in the NR3C1 gene, C-511T in
      IL-1beta gene, and Leu155His and rs2670660/C in NALP1 gene. Patients were grouped
      as responder, dependant, and resistant to GCs. The relation between GC response
      and the genetic polymorphisms considered was examined using univariate,
      multivariate, and Classification and Regression Tree (CART) analysis. RESULTS:
      Univariate analysis showed that BclI polymorphism was more frequent in responders
      compared with dependant patients (P=0.03) and with the combined dependant and
      resistant groups (P=0.02). Moreover, the NALP1 Leu155His polymorphism was less
      frequent in the GC responsive group compared with resistant (P=0.0059) and
      nonresponder (P=0.02) groups. Multivariate analysis comparing responders and
      nonresponders confirmed an association between BclI mutated genotype and steroid
      response (P=0.030), and between NALP1 Leu155His mutant variant and nonresponders
      (P=0.033). An association between steroid response and male sex was also observed
      (P=0.034). In addition, Leu155His mutated genotype was associated with steroid
      resistance (P=0.034). Two CART analyses supported these findings by showing that
      BclI and Leu155His polymorphisms had the greatest effect on steroid response
      (permutation P value=0.046). The second CART analysis also identified age of
      disease onset and male sex as important variables affecting response.
      CONCLUSIONS: These results confirm that genetic and demographic factors may
      affect the response to GCs in young patients with IBD and strengthen the
      importance of studying high-order interactions for predicting response.

PMID- 20697296
TI  - Hexapodal external fixation in the management of children tibial fractures.
AB  - Some tibial fractures in children require surgical osteosynthesis, mostly
      achieved by an internal fixation. Indications for external fixation in the
      management of tibial fractures in children are limited to specific clinical
      situations when conventional treatments are contraindicated. The aim of this
      study is to report the results of tibial fractures management by hexapodal
      external fixation. Eleven children were included in this study and all of them
      were treated by a specific hexapodal external fixator, with a 12-month mean
      follow-up. In the whole series, initial deformities were perfectly corrected in
      nine cases, two patients showed residual deformity that did not require further
      surgery. The mean time for external fixation was 98 days. Hexapodal external
      fixation seems to be a simple and effective definitive method for the correction
      of three-dimensional traumatic deformities requiring surgical stabilization. Long
      term follow-up will be necessary to evaluate residual deformities at the end of
      patient's growth.

PMID- 20697297
TI  - Synovial hemangioma of the knee joint in a 3-year-old girl.
AB  - Synovial hemangioma has been reported to be relatively rare, and usually occurs
      in childhood and adolescence. However, there are a few reports of the disease in
      infants. In this report, we diagnosed synovial hemangioma in a 3-year-old girl
      who had swelling and pain in her left knee. Gadolinium-enhanced magnetic
      resonance imaging revealed abnormal intensity in an intra-articular lesion. We
      performed arthroscopy, and arrived at a final diagnosis based on a scopic biopsy.
      Synovial hemangioma should be considered as a possible diagnosis in infants with
      swelling and pain in the knee.

PMID- 20697298
TI  - Novel epidermal growth factor receptor mutation-specific antibodies for non-small
      cell lung cancer: immunohistochemistry as a possible screening method for
      epidermal growth factor receptor mutations.
AB  - BACKGROUND: Epidermal growth factor receptor (EGFR) mutations in non-small cell
      lung cancer (NSCLC) predict better outcome to EGFR tyrosine kinase inhibitors.
      The most common mutations are exon 19 deletions (most frequently E746-A750) and
      L858R point mutation in exon 21. Here, we evaluated the accuracy of novel EGFR
      mutation-specific antibodies in a Japanese cohort with NSCLC and compared with
      direct DNA sequencing and clinical outcome. MATERIALS AND METHODS:
      Immunohistochemistry (IHC) using antibodies specific for the E746-A750 and L858R
      mutations in EGFR was performed on tissue microarrays of tumors from 70 gefitinib
      treated NSCLC patients. Extracted DNA was sequenced for mutational analysis of
      EGFR exons 18 to 21. RESULTS: DNA sequencing showed EGFR mutations in 41 patients
      (58.6%) and exon 19 deletions in 18 patients (25.7%), 11 of 18 (61%) had a
      deletion in the range of E746-A750 and 12 (17.1%) had exon 21 mutations (L858R).
      IHC showed, for the E746-A750 and L858R mutations, sensitivity (81.8 and 75%),
      specificity (100 and 96.6%), positive predictive value (100 and 81.8%), and
      negative predictive value (96.7 and 94.9%). Analysis for objective response rates
      and survival were not correlated to IHC staining, although the combined staining
      showed nonsignificant trends toward better overall survival for patients with
      EGFR mutations. CONCLUSIONS: The mutation-specific IHC antibodies have high
      sensitivity and specificity for predefined EFGR mutations and may be suitable for
      screening for these predefined mutations. However, negative IHC results require
      further mutation analyses before excluding EGFR-targeted therapy.

PMID- 20697299
TI  - Time course of the neural processing of spoken derived words: an event-related
      potential study.
AB  - Event-related potentials were recorded to examine the time course of the neural
      processing of spoken (i) existing derived words, (ii) morphologically legal, and
      (iii) illegal pseudowords in the Finnish language. The stimuli were matched by
      (complex) uniqueness/deviation points and event-related potentials were time
      locked to stimulus onset and suffix onset. Illegal pseudowords elicited a larger
      negativity than existing words approximately 300 ms after suffix onset,
      suggesting a difficulty to semantically integrate morphemes. The magnitude of the
      negativity effect was similar for legal pseudowords and existing words,
      reflecting successful licensing and integration of morphemes for legal
      pseudowords. The results suggest parallel full-form and morpheme-based processing
      of spoken derived stimuli and emphasize the role of semantic interpretability in
      morphological parsing.

PMID- 20697300
TI  - Long-lasting effects of chemical hypoxia on spinal cord function in tadpoles.
AB  - We investigated the effects of chemical hypoxia on the central pattern generator
      controlling swimming in stage 42 Xenopus laevis larvae. We recorded motoneuron
      activity from ventral roots of immobilized tadpoles and evoked swim episodes by
      brief electrical stimulation of the tail skin. In the presence of the metabolic
      inhibitor, sodium azide (5 mM, NaN3), swim episode duration and cycle frequency
      decreased until swim motor patterns could not be evoked. On recovery, cycle
      frequency returned to preazide levels; however, episode duration remained short
      for at least an hour. In addition, recovery induced spontaneous, short bouts of
      swimming similar to the slow rhythm that is evoked by N-methyl-D-aspartic acid.
      We conclude that abiotic features of the environment can have long-term
      modulatory effects on circuit function in the CNS.

PMID- 20697301
TI  - Learning of musical and linguistic structures: comparing event-related potentials
      and behavior.
AB  - To learn a new language, it is necessary for the learner to succeed in segmenting
      the continuous stream of sounds into significant units. Previous behavioral
      studies have shown that it is possible to segment a language or musical stream
      based only on probabilities of occurrence between adjacent syllables/tones. Here
      we used a sung language and tested participants' learning of both linguistic and
      musical structures while recording electroencephalography. Although behavioral
      results showed learning of the linguistic structure only, event-related potential
      results for both dimensions showed a negative component sensitive to the degree
      of familiarity of items. We discuss this component as an index of lexical search,
      also pointing to the greater sensitivity of the event-related potentials compared
      to the behavioral responses.

PMID- 20697302
TI  - A novel transcriptional regulator of myelin gene expression: implications for
      neurodevelopmental disorders.
AB  - Myelination is critical for normal functioning of mammalian central nervous
      system. Central nervous system myelin is created and maintained by
      oligodendrocytes. Protein expression patterns change as the oligodendrocyte
      progenitors differentiate into myelinating oligodendrocytes. Several proteins,
      including the cell surface proteoglycan NG2, proteolipid protein, myelin basic
      protein, and myelin-associated glycoprotein are critical for normal myelination.
      The molecular regulation of myelination is for the most part unknown, although
      several transcription factors have been identified as regulating myelin protein
      expression. We have identified a known transcriptional regulator, methyl-CpG
      binding protein 2, as regulating myelin specific gene expression in a transgenic
      mouse. Our findings show a potential role for myelin in the pathophysiology of
      methyl-CpG-binding protein 2 mutation-associated disorders.

PMID- 20697303
TI  - Sounding the alarm about metabolic syndrome.

PMID- 20697304
TI  - The evidence that isn't... Interpreting research.

PMID- 20697305
TI  - Will the market dictate nurses' educational levels?

PMID- 20697306
TI  - An inside view of venous thromboembolism.

PMID- 20697307
TI  - Maintenance of activity and eating change after a clinical trial of tailored
      newsletters with older rural women.
AB  - BACKGROUND: In the Wellness for Women Project, a randomized-by-site 1-year
      controlled clinical trial, the efficacy of generic newsletters and newsletters
      tailored on Health Promotion Model behavior-specific cognitions, eating behavior,
      and activity behavior were compared among 225 women aged 50 to 69 years.
      OBJECTIVES: The purpose of this study was to compare the maintenance of change in
      healthy eating and physical activity over the 12 months following the tailored
      versus generic mailed newsletter intervention. METHODS: Outcomes at 18 and 24
      months included behavioral markers and biomarkers of physical activity and
      eating. Data were analyzed using the multivariate approach to repeated measures
      analysis of variance and generalized estimating equations (alpha <.05). RESULTS:
      At 18 months, the tailored group maintained levels of all eating and activity
      behaviors, whereas the generic group maintained levels of fruit and vegetable
      servings, a moderate or greater activity, stretching exercise, lower body
      strength and flexibility but increased saturated fat intake and declined in
      weekly strength exercise and cardiorespiratory fitness. At 24 months, both groups
      maintained or returned to 12-month levels of all eating behaviors,moderate or
      greater activity, stretching exercise, and flexibility but declined in
      cardiorespiratory fitness; the tailored group maintained levels of strength
      exercise and lower body strength, whereas the generic group decreased in both. A
      greater proportion of women who received tailored newsletters continued to
      achieve most Healthy People 2010 criteria for eating and activity. DISCUSSION:
      Mailed tailored print newsletters were more efficacious than generic newsletters
      in facilitating maintenance of change in eating and activity for 6 months
      postintervention. Both tailored and generic newsletters facilitated the
      maintenance of change in eating behaviors and in moderate or greater physical
      activity and stretching exercise, whereas tailored newsletters were more
      efficacious in maintaining change in strength exercise for 12 months
      postintervention.

PMID- 20697308
TI  - The role of optimism in health-promoting behaviors in new primiparous mothers.
AB  - BACKGROUND: Perceived stress has been associated with fewer health-promoting
      behaviors in new primiparous mothers, but less is known about the mechanisms
      responsible for such effects. OBJECTIVE: The objective of this study was to
      examine the hypothesis that the relationship between perceived stress and health
      promoting behaviors is mediated partially by a primiparous mother's sense of
      optimism. The transactional model of stress and coping and the model of
      behavioral self-regulation were used as the theoretical framework for the study.
      METHODS: An ex post facto cross-sectional design was used for this study.
      Participants consisted of 174 primiparous mothers who had given birth within the
      previous 12 months. Participants completed a self-reported online questionnaire
      consisting of the Perceived Stress Scale, the Health-Promoting Lifestyle Profile
      II, and the revised Life Orientation Test. RESULTS: Results indicated that
      perceived stress predicted less health-promoting behaviors in new primiparous
      mothers (p < .001). Importantly, this relationship was mediated partially by the
      optimism displayed by the mother (p < .001). CONCLUSIONS: The findings indicated
      that optimism partially mediated the relationship between perceived stress and
      health-promoting behaviors in new primiparous mothers. The implications for
      psychological practice are discussed.

PMID- 20697309
TI  - Substrate-specific modulation of CYP3A4 activity by genetic variants of
      cytochrome P450 oxidoreductase.
AB  - OBJECTIVES: CYP3A4 receives electrons from P450 oxidoreductase (POR) to
      metabolize about 50% of clinically used drugs. There is substantial inter
      individual variation in CYP3A4 catalytic activity that is not explained by CYP3A4
      genetic variants. CYP3A4 is flexible and distensible, permitting it to
      accommodate substrates varying in shape and size. To elucidate the mechanisms of
      variability in CYP3A4 catalysis, we examined the effects of genetic variants of
      POR, and explored the possibility that substrate-induced conformational changes
      in CYP3A4 differentially affect the ability of POR variants to support catalysis.
      METHODS: We expressed human CYP3A4 and four POR variants (Q153R, A287P, R457H,
      A503 V) in bacteria, reconstituted them in vitro and measured the Michaelis
      constant and maximum velocity with testosterone, midazolam, quinidine and
      erythromycin as substrates. RESULTS: POR A287P and R457H had low activity with
      all substrates; Q153R had 76-94% of wild-type (WT) activity with midazolam and
      erythromycin, but 129-150% activity with testosterone and quinidine. The A503 V
      polymorphism reduced the CYP3A4 activity to 61-77% of WT with testosterone and
      midazolam, but had nearly WT activity with quinidine and erythromycin.
      CONCLUSION: POR variants affect CYP3A4 activities. The impact of a POR variant on
      catalysis by CYP3A4 is substrate-specific, probably because of substrate-induced
      conformational changes in CYP3A4.

PMID- 20697310
TI  - Characterization of 17-dihydroexemestane glucuronidation: potential role of the
      UGT2B17 deletion in exemestane pharmacogenetics.
AB  - OBJECTIVE: Exemestane is a third-generation aromatase inhibitor used in the
      treatment of breast cancer in postmenopausal women. Reduction to form 17
      dihydroexemestane and subsequent glucuronidation to exemestane-17-O-glucuronide
      is a major pathway for exemestane metabolism. The goal of this study was to
      analyze 17-dihydroexemestane anti-aromatase activity, characterize the 17
      dihydroexemestane glucuronidation pathway, and determine whether the functional
      polymorphisms in active UGTs could play a role in altered 17-dihydroexemestane
      glucuronidation. METHODS: Homogenates from a HEK293 aromatase-overexpressing cell
      line (HEK293-aro) were used to examine exemestane versus 17-dihydroexemestane
      anti-aromatase activities. UGT-overexpressing cell lines and a panel (n=110) of
      human liver microsome (HLM) were screened for glucuronidation activity against 17
      dihydroexemestane. UGT2B17 genotyping and liver mRNA expression were performed by
      real-time PCR. RESULTS: The inhibition of estrone formation from androst-4-ene
      3,17-dione in HEK293-aro cell homogenates was similar for 17-dihydroexemestane
      (IC(50)=2.3+/-0.83 MUmol/l) and exemestane (IC(50)=1.4+/-0.42 MUmol/l). UGTs 2B17
      and 1A4 were high-expression hepatic UGTs that exhibited activity against 17
      dihydroexemestane, with UGT2B17 exhibiting a 17-fold higher V(max)/K(M) than
      UGT1A4. The rate of exemestane-17-O-glucuronide formation was shown to be
      significantly (P<0.001) decreased (14-fold) in HLMs exhibiting the UGT2B17(*2/*2)
      deletion genotype versus wild-type UGT2B17(*1/*1) HLMs; a 36-fold lower
      V(max)/K(M) (P=0.023) was observed in UGT2B17(*2/*2) versus UGT2B17(*1/*1) HLMs.
      A significant (P<0.0001, R(2)=0.72) correlation was observed between HLM
      exemestane-17-O-glucuronide formation and liver UGT2B17 expression. CONCLUSION:
      These data suggest that 17-dihydroexemestane is an active metabolite of
      exemestane and that the UGT2B17 deletion polymorphism could play an important
      role in determining levels of excretion of 17-dihydroexemestane and overall
      exemestane metabolism.

PMID- 20697311
TI  - Reconstructive outcomes in patients with sarcoma of the breast.
AB  - BACKGROUND: Primary soft-tissue sarcomas account for less than 1 percent of all
      breast malignancies. Many of these are associated with prior radiation therapy.
      Few studies have evaluated this patient population. The purpose of this study was
      to examine reconstruction techniques and outcomes in a cohort of patients with
      breast sarcoma to elucidate the optimal type and timing of reconstruction.
      METHODS: The authors conducted a retrospective review of all patients diagnosed
      and treated for soft-tissue breast sarcomas between July 1, 1988, and December 9,
      2009, at a tertiary cancer center. Data collected included demographics,
      histology, oncologic and reconstructive treatment, and clinical outcomes.
      RESULTS: Twenty-three breast sarcoma patients underwent 24 reconstructions. The
      mean age at diagnosis was 42 years (range, 17 to 78 years). The most common
      histologic finding was angiosarcoma; six of the 11 angiosarcomas developed
      following irradiation for either breast carcinoma or lymphoma. The median follow
      up was 44 months. Twenty patients were alive through the follow-up period.
      Reconstruction was immediate in 20 cases and delayed in four. The reconstruction
      used autologous tissue in 16 cases, implants in five, and both in three. All
      patients who underwent irradiation during treatment underwent autologous tissue
      reconstruction. Surgical complications included implant displacement, tissue
      expander displacement, total flap loss, seroma, implant exposure, and partial
      skin graft loss. CONCLUSIONS: Soft-tissue breast sarcomas are uncommon and demand
      aggressive, multimodal treatment and well-planned reconstruction. Most sarcoma
      patients receive radiotherapy; to minimize complications, we recommend delayed
      autologous reconstruction after completion of radiotherapy.

PMID- 20697312
TI  - The evolution of mandibular distraction: device selection.
AB  - BACKGROUND: Mandibular distraction has evolved from the use of external to the
      use of intraoral and semiburied devices. The authors highlight the evolution of
      the semiburied technique. The authors evaluate advantages and limitations, and
      report perioperative events for external and semiburied techniques to establish
      the indications for selection of the different devices. METHODS: A retrospective
      review was conducted of patients undergoing mandibular distraction at the New
      York University Langone Medical Center from the authors' introduction of
      mandibular distraction in May of 1989 to June 30, 2009. Perioperative events were
      stratified into three groups: minor incidents, moderate incidents, and major
      incidents. RESULTS: A total of 211 mandibular distraction procedures were
      performed: 129 external procedures on native bone, 37 external procedures on
      grafted bone, and 45 semiburied procedures on native bone. Minor incidents were
      more common with the semiburied device (62 percent) compared with external
      devices on native (26 percent) and grafted (38 percent) bone. There were fewer
      moderate incidents with the semiburied device (18 percent) than with the external
      device on native (22 percent) and grafted (30 percent) bone. In contrast to the
      external technique, no major incidents were seen with semiburied distraction.
      CONCLUSIONS: The semiburied device reduces scarring and has the mechanical
      advantages of being applied directly to the bone, less vulnerable to dislodgment,
      and more favorable for a vertical vector. However, its use requires more bone
      stock and it has the disadvantage of requiring a second operation for removal.
      Semiburied distraction is safe, reliable, and indicated for lengthening of the
      hypoplastic mandible where there is adequate bone stock for its attachment.

PMID- 20697313
TI  - Observational studies: cohort and case-control studies.
AB  - Observational studies constitute an important category of study designs. To
      address some investigative questions in plastic surgery, randomized controlled
      trials are not always indicated or ethical to conduct. Instead, observational
      studies may be the next best method of addressing these types of questions. Well
      designed observational studies have been shown to provide results similar to
      those of randomized controlled trials, challenging the belief that observational
      studies are second rate. Cohort studies and case-control studies are two primary
      types of observational studies that aid in evaluating associations between
      diseases and exposures. In this review article, the authors describe these study
      designs and methodologic issues, and provide examples from the plastic surgery
      literature.

PMID- 20697314
TI  - Health-related quality of life, patient benefit, and clinical outcome after
      otoplasty using suture techniques in 62 children and adults.
AB  - BACKGROUND: The available medical literature lacks data about the effect of
      otoplasty on health-related quality of life. METHODS: In the present study, 84
      patients, having received otoplasty using a suture technique, were asked to
      answer validated questionnaires (the Glasgow Benefit Inventory and the Glasgow
      Children's Benefit Inventory, respectively); Glasgow Benefit Inventory and
      Glasgow Children's Benefit Inventory scores can range from -100 (maximal adverse
      effect) through 0 (no effect) to 100 (maximal positive effect). RESULTS: Sixty
      two patients (73.8 percent) returned a valid questionnaire. For the adults'
      cohort (n=21), the mean total Glasgow Benefit Inventory score was 30.6; 100.0
      percent were satisfied with the aesthetic result, and 90.5 percent would again
      decide in favor of the operation. For the children's cohort (n=41), the mean
      total Glasgow Children's Benefit Inventory score was 24.1; 95.1 percent of the
      parents and 95.1 percent of the children were satisfied with the aesthetic
      result; and 97.6 percent of the parents and 92.7 percent of the children would
      again decide in favor of the operation. The health-related quality of life was
      elevated in 95.2 percent of the adults and 95.1 percent of the children. The
      additional compilation of clinical outcome parameters and complications confirmed
      the effectiveness and safety of an otoplasty using suture techniques. CONCLUSION:
      Otoplasty using suture techniques can significantly increase patients' health
      related quality of life and leads to a high rate of patient satisfaction.

PMID- 20697315
TI  - Microvascular reconstruction of oncologic defects of the midface.
AB  - Reconstruction of a midfacial defect can represent a formidable challenge for the
      reconstructive surgeon. Attesting to both the variety and the complexity of
      midfacial defects, numerous different classification schemes have been proposed,
      and are reviewed in this article. The approach to reconstruction can be
      simplified, however, by classifying maxillectomy defects into four types.
      Understanding the complex three-dimensional anatomy of the maxilla and its
      relationship to contiguous structures is the first step in approaching
      reconstruction of the midface. Achieving basic functional and aesthetic goals of
      maxillary reconstruction can be achieved using free flap reconstruction with good
      reliability and predictability in the majority of patients. A specific approach
      to each defect type is outlined.

PMID- 20697316
TI  - The National Practitioner Data Bank: issues in plastic surgery.
AB  - BACKGROUND: The purpose of this article is to increase awareness among plastic
      surgeons of the applications and implications of the National Practitioner Data
      Bank. METHODS: A literature review using PubMed and Google was conducted
      regarding the history, function, and outcomes of the National Practitioner Data
      Bank, a federally maintained database of malpractice payments and disciplinary
      actions involving licensed healthcare providers. Particular attention was paid to
      institutional reporting requirements, the process of querying the data bank, and
      controversies regarding the effectiveness of the data bank as they apply to
      physicians. RESULTS: Many physicians in practice and training remain unaware of
      the requirements of the data bank. Specifically, situations in which an
      institution must report to the National Practitioner Data Bank on a physician's
      behalf can be surprising, such as payment to a patient in settlement of written
      claim without the suggestion of malpractice, denial of additional credentialing,
      and suspension of privileges for greater than 30 days. Mandatory and voluntary
      querying of the National Practitioner Data Bank also varies among entities. A
      listing with the National Practitioner Data Bank can have consequences for
      licensure and credentialing throughout a physician's career, and reporting
      requirements begin as an intern. Lastly, it is not clear that the existence of
      the National Practitioner Data Bank has improved the quality of health care in
      the United States. CONCLUSION: Knowledge of the requirements and limitations of
      the National Practitioner Data Bank is useful for plastic surgeons because of the
      diverse implications of its contents for their current and future practices.

PMID- 20697317
TI  - High- and extra-high-projection breast implants: potential consequences for
      patients.
AB  - All breast implants can potentially have deleterious effects on patients'
      tissues. Limiting negative tissue consequences and potential uncorrectable
      deformities requires that surgeons be aware and educate patients regarding
      potential consequences of various implant designs. High-profile implants have
      been available for decades, and during the current decade, extra-high-profile
      implants have become available, but no valid peer-reviewed and published studies
      have compared the potential tissue consequences of these designs to those of
      other breast implant designs. Valid comparative studies are exceedingly difficult
      to perform because of the number of variables that must be addressed to establish
      valid comparative cohorts. Nevertheless, the potential occurrence of negative
      tissue consequences from high- and extra-high-profile implants in primary breast
      augmentation and breast augmentation reoperation cases is well known to
      experienced aesthetic breast surgeons. This article addresses potential negative
      effects on patients' tissues of high- and extra-high-profile breast implants used
      for breast augmentation. This Special Topic article is not structured or intended
      as a scientific article. It is written as a Special Topic and not an Editorial at
      the editor's request. The cases presented are selected examples to illustrate
      potential clinical eventualities. The rate of occurrence of uncorrectable tissue
      deformities relates directly to surgeon and patient awareness of the potential
      consequences of implant selection decisions and requests. To minimize risks of
      negative tissue consequences for patients, surgeon awareness, patient education,
      and optimal implant selection decision processes are essential.

PMID- 20697318
TI  - A qualitative analysis of the decision-making process for patients with severe
      lower leg trauma.
AB  - BACKGROUND: Choosing the appropriate treatment for grade IIIB and IIIC open
      tibial fractures is a difficult decision for both the patient and the physician.
      Current research shows that the functional outcomes for reconstruction are
      similar to those for below-knee amputation, but little investigation of the
      qualitative outcomes of either treatment option has been performed from the
      patient perspective. This study was designed to perform a qualitative analysis of
      patient preferences for amputation or reconstruction. METHODS: Twenty patients
      with type IIIB or IIIC open tibial fractures participated in the study. These
      patients had undergone either amputation or reconstruction between 1997 and 2007.
      Semistructured interviews were conducted and qualitative outcomes were assessed.
      RESULTS: Interviews highlighted several issues involved with medical decision
      making. Participants described not having a role in deciding which medical
      treatment to choose. Family and spouses played a greater role, often because of
      patients being medicated when needing to make a treatment choice. Both amputation
      and reconstruction patients described being satisfied with the outcomes of their
      surgical treatments, but also expressed second thoughts about their treatment
      choices. CONCLUSIONS: The findings of this study emphasize how difficult it is to
      assign preference to one medical treatment over another. The study reveals how
      the role of the patient is limited in making a decision about pursuing amputation
      or reconstruction. Instead, there is a continued need for physicians to discuss
      treatment options and risks with family members who act on the patient's behalf,
      and to incorporate the patient's preference in this complex decision.

PMID- 20697319
TI  - Do not use epinephrine in digital blocks: myth or truth? Part II. A retrospective
      review of 1111 cases.
AB  - BACKGROUND: Epinephrine in digital blocks has been condemned by traditional
      medical theory. The authors provide a retrospective review of 1111 cases
      involving digital block anesthesia with epinephrine in conjunction with an
      extensive literature review. METHODS: The authors conducted a retrospective
      review of 1111 cases involving digital and hand surgery. Observations were made
      concerning the location of and indication for surgery, age, sex, type of block
      used, type and dose of anesthetic, use of epinephrine and concentration, use of a
      tourniquet, follow-up, and complications. Dorsal and transthecal techniques were
      used exclusively. Patients with vascular compromise did not receive epinephrine
      and were excluded from the study. RESULTS: One thousand one hundred eleven cases
      were reviewed, distributed among 692 male patients and 419 female patients. Sites
      of surgery ranged throughout the hand and all fingers for a variety of
      indications. Five hundred patients received injections of 1% plain lidocaine with
      a dosage range of 2 to 10 cc and an average of 5.7 cc. Six hundred eleven
      patients received injections of 1% lidocaine with epinephrine (1:100,000) in a
      dose range of 0.5 to 10 cc and an average dose of 4.33 cc. Nine hundred eighty
      six patients (88.75 percent) followed up in the clinic. No patients suffered from
      digital gangrene in the epinephrine group. CONCLUSIONS: After reviewing 1111
      cases, there were no complications associated with the use of epinephrine in
      digital blocks. The authors suggest that correct application of epinephrine in
      digital blocks is appropriate, and defend its use.

PMID- 20697320
TI  - Adenosquamous carcinoma of the pancreas: a distinct clinicopathologic entity.
AB  - Among exocrine pancreatic tumors, adenosquamous carcinoma (ASC) is a rare,
      aggressive subtype with a worse prognosis and a higher potential for metastases
      compared to its more conventional glandular counterpart, adenocarcinoma. The
      disease distribution shows an approximately 1:1 male/female ratio and a median
      survival of circa five months. Although such features as central necrosis and
      hypervascularity are suggestive of pancreatic ASC, more research is necessary to
      identify other, more specific markers for this tumor subtype. Humoral
      hypercalcemia of malignancy has also been described with ASC of the pancreas,
      likely as a result of PTHrP production by the squamous component of the tumor.
      Similar to the therapeutics of pancreatic adenocarcinoma, adjuvant chemotherapy
      or chemoradiotherapy is currently indicated for resectable ASC of the pancreas,
      while gemcitabine or gemcitabine combinations are used for a more advanced
      disease. Both pathologic and molecular features of pancreatic ASC characterize it
      as a distinct subtype of pancreatic cancer. As a result, its molecular and
      genetic makeup could be exploited for both diagnostic and therapeutic quests in
      the future.

PMID- 20697321
TI  - Clostridium difficile: an update for the primary care clinician.
AB  - Clostridium difficile infection (CDI) is an important cause of intestinal
      disease, primarily affecting hospitalized patients exposed to antibiotics.
      Infection has been associated with prolonged hospital stays and excess healthcare
      expenditures. Recent changes in the epidemiology, pathogenesis, and treatment of
      CDI have occurred, leading to renewed scrutiny of this pathogen. Increases in its
      incidence and severity have been documented, possibly due to the emergence of a
      hypervirulent strain that produces high levels of toxins. Community-acquired
      cases in individuals without traditional risk factors have been reported.
      Furthermore, oral metronidazole may not be as effective as oral vancomycin for
      patients with severe CDI. New therapies are being investigated for patients with
      recurrent disease. This review highlights the new developments in the
      epidemiology, pathogenesis, and management of CDI, serving as an up-to-date
      resource for primary care clinicians.

PMID- 20697322
TI  - Coexistence of cerebral tubers with neurocysticercosis.
AB  - Tuberous sclerosis (TS) is a well-recognized cause of symptomatic seizures, and
      rarely coexists with acquired lesions such as neurocysticercosis. We present a 6
      year-old boy with tuberous sclerosis and a limited form of epileptic spasms who
      had, in addition, two coexisting cerebral cysticercal cysts. The association was
      an incidental finding, but the cerebral tubers could be mistaken for perilesional
      edema of cysticercal cysts, especially if the clinical features of TS were subtle
      and not carefully looked for. Our case illustrates the diagnostic and therapeutic
      implications of recognizing the proximate cause of seizures, such as TS, when the
      incidental finding of cysticercal cysts might confound the clinical picture in
      endemic areas.

PMID- 20697323
TI  - Is it time to prospectively match human leukocyte antigen proteins for lung
      transplantation?

PMID- 20697324
TI  - Long-term survival of composite hemiface/mandible/tongue allografts correlates
      with multilineage chimerism development in the lymphoid and myeloid compartments
      of recipients.
AB  - BACKGROUND: To maximize aesthetic and functional outcomes for complex
      craniofacial defects, application of composite tissue allografts opens unique one
      stage reconstructive option. We have assessed role of different components of the
      hemiface/mandible/tongue allograft on induction and maintenance of donor-specific
      chimerism, in correlation with allograft survival. METHODS: Twenty-two composite
      hemiface/mandible/tongue transplantations were performed in three groups: group 1
      (n=8)-isotransplantations between Lewis (LEW) rats (RT1)-served as controls.
      Group 2 (n=8)-allograft rejection controls-hemiface/mandible/tongue transplants
      performed across major histocompatibility complex (MHC) barrier between
      semiallogeneic LEW-Brown-Norway (RT1) donors and LEW (RT1) recipients without
      immunosuppression. Allografts in group 3 (n=6) received tapered cyclosporine A
      monotherapy. Assessments included monitoring of rejection, flow cytometry for
      donor-specific chimerism of major histocompatibility complex class I (RT1)
      antigen, immunohistochemistry for engraftment of donor-origin cells into lymphoid
      organs and bone marrow (BM) compartment, and histology for
      hemiface/mandible/tongue architecture. RESULTS: Isograft controls survived
      indefinitely; in allografts without treatment, rejection started within 5 to 7
      days. Treated hemiface/mandible/tongue allotransplants survived up to 385 days,
      without signs of rejection or graft loss. Flap angiography confirmed intact
      vascularity, and computer tomography scan and histology confirmed bone viability.
      Donor-specific chimerism at day 125 was present for T cells (3.3% CD4/RT1, 1.1%
      CD8/RT1) and B cells (6.7% CD45RA/RT1). Engraftment of donor-origin cells was
      confirmed into BM compartment and lymphoid organs of recipients. CONCLUSIONS: We
      introduced a new multitissue model of composite hemiface/mandible/tongue
      allograft containing lymphoid and vascularized BM components. Long-term allograft
      survival correlated with development and maintenance of donor-specific chimerism
      in lymphoid organs and BM compartment.

PMID- 20697325
TI  - Long-term impact of donor-recipient size mismatching in deceased donor kidney
      transplantation and in expanded criteria donor recipients.
AB  - BACKGROUND: The degree to which recipient/donor (R/D) size mismatching leads to
      nephron underdosing and worse kidney allograft survival remains poorly defined,
      particularly in the setting of preexisting nephron loss such as the expanded
      criteria donor (ECD). METHODS: We performed a retrospective analysis of 69,737
      deceased donor transplants followed by a subset analysis of ECD transplants using
      data from the Scientific Registry of Transplant Recipients from 1992 to 2005.
      Ratios of R/D body surface area (BSA) were used to estimate nephron disparity and
      segregate pairs. RESULTS: In the entire cohort, severe BSA disparity (R/D
      BSA>1.38 m) was associated with slightly worse 10-year unadjusted graft survival
      (35% for severe BSA disparity vs. 39% in pairs of comparable size, P<0.0001). In
      multivariate analysis, BSA disparity was associated with a 15% increased risk of
      graft loss (hazard ratio 1.15, P<0.0001). Within ECD cohorts, severe BSA
      disparity was associated with a decrease in 10-year unadjusted graft survival of
      greater magnitude than the overall cohort (10% for severe BSA disparity vs. 22%
      in pairs of comparable size, P<0.0004). On multivariate analysis, severe R/D BSA
      disparity was associated with worse allograft survival similar to the entire
      cohort (hazard ratio 1.18, P=0.04). CONCLUSIONS: Recipients receiving kidneys
      from substantially smaller donors have a statistically higher rate of graft loss
      that is more pronounced in ECD kidneys. Although severe R/D size disparity is an
      independent risk factor for graft loss, the magnitude of this risk requires
      consideration in the context of other risk factors for the graft loss and the
      hazards of dialysis.

PMID- 20697326
TI  - CP-690550, a Janus kinase inhibitor, suppresses CD4+ T-cell-mediated acute graft
      versus-host disease by inhibiting the interferon-gamma pathway.
AB  - BACKGROUND: Acute graft-versus-host disease (GVHD) is a critical obstacle to bone
      marrow transplantation. Although numerous studies have described
      immunosuppression protocols to mitigate acute GVHD, the need still exists for a
      more efficient immunosuppressant with fewer side effects. Here, we evaluated the
      protective effect of CP-690550, a newly developed Janus kinase inhibitor, in an
      acute GVHD model. METHODS: CP-690550 was chemically synthesized. Acute GVHD was
      induced through the transfer of parent B6 (H-2) bone marrow and CD4 T cells into
      lethally irradiated (B6*bm12)F1 (H-2) mice. RESULTS.: CP-690550 treatments
      confined to days -3 to 11 of GVHD induction provided full protection against
      allogeneic, acute GVHD-related lethality and histopathology. An analysis of the
      initial donor-derived CD4 T-cell responses revealed that the inhibitory effects
      of CP-690550 were largely related to the suppression of donor CD4 T-cell-mediated
      interferon (IFN)-gamma production. Enhanced inhibition of T helper 1 cell
      differentiation, rather than the inhibition of allogeneic CD4 T-cell
      proliferation or T helper 17 cell differentiation, was also confirmed in
      allogeneic mixed lymphocyte reactions. Because lethality was considerably delayed
      by the systemic blockade of IFN-gamma, the principal protective effect of CP
      690550 occurred through the modulation of IFN-gamma production. CONCLUSION: The
      targeting of Janus kinase with a sensitive and specific inhibitor, CP-690550,
      conferred effective protection from acute GVHD induced by a semiallogeneic major
      histocompatibility complex class II-disparate combination. Protection from acute
      GVHD was largely mediated by the inhibition of IFN-gamma production.

PMID- 20697327
TI  - Quantitative assessment of beta-cell apoptosis and cell composition of isolated,
      undisrupted human islets by laser scanning cytometry.
AB  - BACKGROUND: Assays for assessing human islet cell quality, which provide results
      before transplantation, would be beneficial to improve the outcomes for islet
      transplantation therapy. Parameters such as percent beta-cell apoptosis and cell
      composition are found to vary markedly between different islet preparations and
      may serve as markers of islet quality. We have developed fluorescence-based
      assays using laser scanning cytometry for assessing beta-cell apoptosis and islet
      cell composition on serial sections of intact isolated islets. METHODS: Isolated
      human islets were fixed in formalin and embedded in paraffin. Serial sections
      were immunostained for the pancreatic hormones and acinar and ductal cell
      markers. DNA fragmentation was used to label apoptotic cells. Stained cells were
      quantified using an iCys laser scanning cytometer. RESULTS: Islet preparations
      from 102 human pancreatic islet isolations were analyzed. For the whole set of
      islet preparations, we found a mean islet cell composition of 54.5%+/-1.2%
      insulin-positive, 33.9%+/-1.2% glucagon, 12.1%+/-0.7% somatostatin, and 1.5%+/
      0.2% pancreatic polypeptide-positive cells. The apoptotic beta cells were 2.85%+/
      0.4% with a range of 0.27% to 18.3%. The percentage of apoptotic beta cells
      correlated well (P<0.0001, n=59) with results obtained in vivo by transplantation
      of the corresponding islets in diabetic NODscid mice. CONCLUSIONS: The analysis
      of whole, nondissociated islets for cell composition and beta-cell apoptosis
      using laser scanning cytometry gives reliable and reproducible results and could
      be performed both before islet transplantation and on preserved cell blocks at
      any time in future. Thus, they can be a powerful tool for islet quality
      assessment.

PMID- 20697328
TI  - In renal transplants with delayed graft function chemokines and chemokine
      receptor expression predict long-term allograft function.
AB  - BACKGROUND: Chronic loss of renal allograft function is associated with
      interstitial fibrosis and tubular atrophy (IF/TA). Independent of the underlying
      reason, one initial step in the development of fibrosis is chemokine-driven
      invasion of leukocytes from the blood vessels into the allograft. We studied the
      role of chemokines in kidney allografts with delayed graft function and the
      subsequent long-term outcome of renal function and fibrosis. METHODS: We examined
      repetitive biopsies of 30 patients without signs of acute rejection but with
      initially delayed graft function for IF/TA. In addition, we examined the
      expression of chemokine receptor (CCR)-1 and CCR2 on invaded leukocytes and
      macrophages and the corresponding ligands regulated upon activation, normal t
      cell expressed, and secreted (RANTES) and monocyte chemotactic protein-1 on
      residential kidney cells. RESULTS: The initial expression of CCR1 positive
      invading cells and RANTES in glomerular cells correlated with the allograft
      function 12 months after transplantation and at last follow-up. The expression
      was independent of donor characteristics such as age, gender, infectious state,
      cause of death, or use of vasopressive agents. Furthermore, it did not correlate
      with the duration of cold ischemia time. Among the patients with the most
      progressive loss of allograft function follow-up biopsy specimen did not reveal
      any signs of rejection but showed increased CCR1 and RANTES expression in the
      interstitium suggesting ongoing inflammation and fibrosis. CONCLUSION: An early
      expression of RANTES in renal allografts with delayed graft function with
      consecutive invasion of CCR1 positive cells seems to promote ongoing IF/TA and to
      worse renal allograft outcome.

PMID- 20697330
TI  - Global forum for health research, forum 2009: innovating for the health of all.

PMID- 20697331
TI  - Shaping a research agenda to solve health problems: Niviola Cabrera, MD, director
      of science and technology, ministry of public health, Cuba. Interview by Gail
      Reed.

PMID- 20697329
TI  - Policy statement of Canadian Society of Transplantation and Canadian Society of
      Nephrology on organ trafficking and transplant tourism.

PMID- 20697332
TI  - Three-pronged innovation to improve care for acute myocardial infarction patients
      in Cuba.

PMID- 20697333
TI  - Limited financial resources need not mean poor health outcomes.

PMID- 20697334
TI  - Prevalence of stroke and associated risk factors in older adults in Havana City
      and Matanzas Provinces, Cuba (10/66 population-based study).
AB  - INTRODUCTION: Cerebrovascular disease (CVD) is the third cause of death and
      second cause of disability and dementia in adults aged>or=65 years worldwide. The
      few epidemiological studies of stroke in Latin America generally report lower
      prevalence and different patterns than developed countries. OBJECTIVE: Estimate
      the prevalence of stroke and associated risk factors in adults aged>or=65 years
      in Havana City and Matanzas provinces, Cuba. METHODS: Single phase, cross
      sectional, door-to-door study of 3015 adults aged>or=65 years in selected
      municipalities of Havana City and Matanzas provinces. Variables studied were age,
      sex, educational level, and self-report and description of chronic disease
      (stroke, heart attack, angina, and diabetes mellitus), substance use (alcohol,
      tobacco), and dietary habits. Respondents were given a structured physical and
      neurological exam, and blood pressure was measured. Laboratory tests comprised
      complete blood count, fasting glucose, total cholesterol and fractions,
      triglycerides, and apolipoprotein E (APOE) genotype. Diagnosis of stroke was
      based on the World Health Organization's definition. Stroke prevalence ratios
      (crude and adjusted), with 95% confidence intervals (CI), were calculated for the
      variables studied using a Poisson regression model. Risk association was analyzed
      using multiple logistic regression for dichotomous responses. RESULTS:
      Assessments were made of 2944 older adults (97.6% response rate). Prevalence of
      stroke was 7.8% (95% CI 6.9-8.8), and was higher in men. The risk profile for
      this population group included history of hypertension (OR 2.8; 95% CI 2.0-4.0),
      low HDL cholesterol (OR 2.6; 95% CI 1.7-3.9), male sex (OR 1.7; 95% CI 1.2-2.5),
      anemia (OR 1.6; 95% CI 1.1-2.5), history of ischemic heart disease (OR 1.5; 95%
      CI 1.0-2.3), carrier of one or two apolipoprotein E4 genotype (APOE E4) alleles
      (OR 1.4; 95% CI 1.0-2.0), and advanced age (OR 1.3; 95% CI 1.1-1.9). CONCLUSIONS:
      Stroke prevalence in this study is similar to that reported for Europe and North
      America, and higher than that observed in other Latin American countries. The
      risk profile identified includes classic risk factors plus anemia and APOE E
      genotype.

PMID- 20697335
TI  - Efficacy and safety of iorEPOCIM for chemotherapy- or radiotherapy-induced anemia
      in pediatric cancer patients.
AB  - INTRODUCTION: Recombinant human erythropoietin (RHuEPO) is an erythropoiesis
      stimulating agent (ESA) used to treat anemia in patients with total or relative
      erythropoietin deficit. In cancer patients, it is administered to optimize
      hemoglobin (Hb) levels, correct anemia and reduce the need for transfusions. Cuba
      produces a RHuEPO, registered in 1998 as iorEPOCIM, that is widely used in the
      national public health system, mainly to treat patients with anemia due to
      chronic kidney disease (CKD). OBJECTIVE: Evaluate the efficacy and safety of
      iorEPOCIM in pediatric cancer patients with anemia following chemotherapy or
      radiotherapy. The working hypothesis posed an Hb increase>or=15 g/l in 70% of
      patients receiving iorEPOCIM for 8 weeks. METHODS: A Phase IV, multicenter, open
      clinical trial was conducted. Participants were 157 patients aged 1-19 years with
      anemia and cyto-histological diagnosis of cancer in any location. Patients
      received either 600 U/kg iorEPOCIM intravenously, once weekly, or 150 U/kg
      iorEPOCIM subcutaneously, 3 times a week, for 8 weeks. All patients had blood
      tests every week to determine hemoglobin and hematocrit, and reticulocyte and
      platelet counts. Mean number of transfusions required by patients during the
      treatment period was compared to the mean number of transfusions received in the
      preceding 8 weeks. Adverse events (AE) were recorded at the 4th and 8th weeks and
      classified by intensity and causality. RESULTS: Hb levels rose>or=15 g/l in 68.8%
      of patients, and transfusion requirements decreased 17%. The most frequent
      adverse events were fever (19.3%), vomiting (10.2%) and flu-like syndrome (9.6%).
      Intensity of AE was predominantly mild. Only 7 AE were classified as very
      probably related to the product and none of those was severe. CONCLUSIONS:
      iorEPOCIM proved to be safe and effective at the doses and frequencies used in
      this patient population. As a result, this medication was recommended for use in
      all pediatric oncology and hematology services in the country.

PMID- 20697336
TI  - Cuba and Brazil: an important example of South-South collaboration in health
      biotechnology.
AB  - This article analyzes the entrepreneurial cooperation between Cuba and Brazil in
      health biotechnology. It looks at the strategies applied and the main impacts.
      The respective government/political wills and the corresponding South-South
      collaboration policies are discussed, as well as the steps taken to materialize
      collaboration programs, including joint production of a meningitis vaccine for
      Africa. This cooperation is a good example of how South-South collaboration can
      be a useful tool to promote capacity building and provide cost-effective health
      solutions for developing countries.

PMID- 20697337
TI  - Overcoming barriers to improved research on the social determinants of health.
AB  - This paper examines the recommendations of the World Health Organization's
      Commission on the Social Determinants of Health regarding the need for improved
      research on determinants of health inequity and discusses the following barriers
      to implementation of those recommendations: the power of the biomedical
      imagination in health and medical research; emphasis on vertical health
      programming; ideological biases outweighing evidence in policy decisions; and
      academic reward systems, including the inherent conservatism of peer review. The
      paper concludes with suggestions for changing research funding and assessment
      systems to overcome these barriers.

PMID- 20697338
TI  - Once the earth stood still (Part II): Mental health services in post-quake Haiti.

PMID- 20697339
TI  - Innovations for global health equity: beyond open access towards open data.

PMID- 20697340
TI  - Armodafinil (Nuvigil) for wakefulness.

PMID- 20697341
TI  - Aztreonam for inhalation solution (Cayston) for cystic fibrosis.

PMID- 20697342
TI  - Nutritional support for macular degeneration.

PMID- 20697344
TI  - Functional importance of RASSF1A microtubule localization and polymorphisms.
AB  - Ras association domain family protein 1A (RASSF1A) is one of the more heavily
      methylated genes in human cancers. In addition to promoter-specific methylation,
      RASSF1A polymorphisms have been identified in cancer patients. RASSF1A is a tumor
      suppressor protein involved in death receptor-dependent apoptosis and it is
      localized to microtubules. Currently, the biological importance of RASSF1A
      microtubule localization and the functional consequences of RASSF1A polymorphisms
      is not understood. In this study, we have investigated both RASSF1A microtubule
      association and polymorphisms. Loss of RASSF1A microtubule association resulted
      in the nuclear appearance of RASSF1A and the loss of association with alpha-,
      gamma- and beta-tubulin. Moreover, the loss of microtubule localization of
      RASSF1A resulted in enhanced tumor-promoting potential, as determined by a
      xenograft transplantation model in nude mice. It is surprising that, several
      RASSF1A polymorphisms also lost the ability to associate with alpha-, gamma- and
      beta-tubulin and lost the ability to prevent tumor formation in a xenograft nude
      mouse model when compared with wild-type RASSF1A. Our results demonstrate a role
      for RASSF1A microtubule localization in eliciting its tumor suppressor function.
      In addition, some RASSF1A polymorphisms lack the tumor suppressor function of
      RASSF1A and, if present in patients, may be tumorigenic.

PMID- 20697343
TI  - Trisomic dose of several chromosome 21 genes perturbs haematopoietic stem and
      progenitor cell differentiation in Down's syndrome.
AB  - Children with Down's syndrome (DS) have 20-50-fold higher incidence of all
      leukaemias (lymphoid and myeloid), for reasons not understood. As incidence of
      many solid tumours is much lower in DS, we speculated that disturbed early
      haematopoietic differentiation could be the cause of increased leukaemia risk. If
      a common mechanism is behind the risk of both major leukaemia types, it would
      have to arise before the bifurcation to myeloid and lymphoid lineages. Using the
      transchromosomic system (mouse embryonic stem cells (ESCs)) bearing an extra
      human chromosome 21 (HSA21)) we analyzed the early stages of haematopoietic
      commitment (mesodermal colony formation) in vitro. We observed that trisomy 21
      (T21) causes increased production of haemogenic endothelial cells, haematopoietic
      stem cell precursors and increased colony forming potential, with significantly
      increased immature progenitors. Transchromosomic colonies showed increased
      expression of Gata-2, c-Kit and Tie-2. A panel of partial T21 ESCs allowed us to
      assign these effects to HSA21 sub-regions, mapped by 3.5 kbp-resolution tiling
      arrays. The Gata-2 increase on one side, and c-Kit and Tie-2 increases on the
      other, could be attributed to two different, non-overlapping HSA21 regions. Using
      human-specific small interfering RNA silencing, we could demonstrate that an
      extra copy of RUNX1, but not ETS-2 or ERG, causes an increase in Tie-2/c-Kit
      levels. Finally, we detected significantly increased levels of RUNX1, C-KIT and
      PU.1 in human foetal livers with T21. We conclude that overdose of more than one
      HSA21 gene contributes to the disturbance of early haematopoiesis in DS, and that
      one of the contributors is RUNX1. As the observed T21-driven hyperproduction of
      multipotential immature precursors precedes the bifurcation to lymphoid and
      myeloid lineages, we speculate that this could create conditions of increased
      chance for acquisition of pre-leukaemogenic rearrangements/mutations in both
      lymphoid and myeloid lineages during foetal haematopoiesis, contributing to the
      increased risk of both leukaemia types in DS.

PMID- 20697345
TI  - Somatic p16(INK4a) loss accelerates melanomagenesis.
AB  - Loss of p16(INK4a)-RB and ARF-p53 tumor suppressor pathways, as well as
      activation of RAS-RAF signaling, is seen in a majority of human melanomas.
      Although heterozygous germline mutations of p16(INK4a) are associated with
      familial melanoma, most melanomas result from somatic genetic events: often
      p16(INK4a) loss and N-RAS or B-RAF mutational activation, with a minority
      possessing alternative genetic alterations such as activating mutations in K-RAS
      and/or p53 inactivation. To generate a murine model of melanoma featuring some of
      these somatic genetic events, we engineered a novel conditional p16(INK4a)-null
      allele and combined this allele with a melanocyte-specific, inducible CRE
      recombinase strain, a conditional p53-null allele and a loxP-stop-loxP
      activatable oncogenic K-Ras allele. We found potent synergy between melanocyte
      specific activation of K-Ras and loss of p16(INK4a) and/or p53 in
      melanomagenesis. Mice harboring melanocyte-specific activated K-Ras and loss of
      p16(INK4a) and/or p53 developed invasive, unpigmented and nonmetastatic melanomas
      with short latency and high penetrance. In addition, the capacity of these
      somatic genetic events to rapidly induce melanomas in adult mice suggests that
      melanocytes remain susceptible to transformation throughout adulthood.

PMID- 20697346
TI  - MUC4 mucin-induced epithelial to mesenchymal transition: a novel mechanism for
      metastasis of human ovarian cancer cells.
AB  - The acquisition of invasiveness in ovarian cancer (OC) is accompanied by the
      process of epithelial-to-mesenchymal transition (EMT). The MUC4 mucin is
      overexpressed in ovarian tumors and has a role in the invasiveness of OC cells.
      The present study was aimed at evaluating the potential involvement of MUC4 in
      the metastasis of OC cells by inducing EMT. Ectopic overexpression of MUC4 in OC
      cells (SKOV3-MUC4) resulted in morphological alterations along with a decreased
      expression of epithelial markers (E-cadherin and cytokeratin (CK)-18) and an
      increased expression of mesenchymal markers (N-cadherin and vimentin) compared
      with the control cells (SKOV3-vector). Also, pro-EMT transcription factors
      TWIST1, TWIST2 and SNAIL showed an upregulation in SKOV3-MUC4 cells. We further
      investigated the pathways upstream of N-cadherin, such as focal adhesion kinase
      (FAK), MKK7, JNK1/2 and c-Jun, which were also activated in the SKOV3-MUC4 cells
      compared with SKOV3-vector cells. Inhibition of phospho-FAK (pFAK) and pJNK1/2
      decreased N-cadherin expression in the MUC4-overexpressing cells, which further
      led to a significant decrease in cellular motility. Knockdown of N-cadherin
      decreased the activation of extracellular signal-regulated kinase-1/2 (ERK1/2),
      AKT and matrix metalloproteinase 9 (MMP9), and inhibited the motility in the
      SKOV3-MUC4 cells. Upon in vivo tumorigenesis and metastasis analysis, the SKOV3
      MUC4 cells produced significantly larger tumors and demonstrated a higher
      incidence of metastasis to distance organs (peritoneal wall, colon, intestine,
      stomach, lymph nodes, liver and diaphragm). Taken together, our study reveals a
      novel role for MUC4 in inducing EMT through the upregulation of N-cadherin and
      promoting metastasis of OC cells.

PMID- 20697347
TI  - The reactive tumor microenvironment: MUC1 signaling directly reprograms
      transcription of CTGF.
AB  - The MUC1 cytoplasmic tail (MUC1.CT) conducts signals from spatial and
      extracellular cues (growth factor and cytokine stimulation) to evoke a
      reprogramming of the cellular transcriptional profile. Specific phosphorylated
      forms of the MUC1.CT achieve this function by differentially associating with
      transcription factors and redirecting their transcriptional regulatory
      capabilities at specific gene regulatory elements. The specificity of interaction
      between MUC1.CT and several transcription factors is dictated by the
      phosphorylation pattern of the 18 potential phosphorylation motifs within the
      MUC1.CT. To better appreciate the scope of differential gene expression triggered
      by MUC1.CT activation, we performed microarray gene expression analysis and
      chromatin immunoprecipitation (ChIP)-chip promoter analysis and identified the
      genome-wide transcriptional targets of MUC1.CT signaling in pancreatic cancer. On
      a global scale, MUC1.CT preferentially targets genes related to invasion,
      angiogenesis and metastasis, suggesting that MUC1.CT signaling contributes to
      establishing a reactive tumor microenvironment during tumor progression to
      metastatic disease. We examined in detail the molecular mechanisms of MUC1.CT
      signaling that induces the expression of connective tissue growth factor
      (CTGF/CCN2), a potent mediator of ECM remodeling and angiogenesis. We demonstrate
      a robust induction of CTGF synthesis and secretion in response to serum factors
      that is enabled only when MUC1 is highly expressed. We demonstrate the
      requirement of phosphorylation at distinct tyrosine motifs within the MUC1.CT for
      MUC1-induced CTGF expression and demonstrate a phosphorylation-specific
      localization of MUC1.CT to the CTGF promoter. We found that MUC1 reorganizes
      transcription factor occupancy of genomic regions upstream of the CTGF gene,
      directing beta-catenin and mutant p53 to CTGF gene regulatory elements to promote
      CTGF expression and destabilizing the interaction at these regions of the
      transcriptional repressor, c-Jun. With this example we illustrate the capacity of
      MUC1.CT to mediate transcription factor activity in a context-dependent manner to
      achieve wide spread and robust changes in gene expression and facilitate creation
      of the reactive tumor microenvironment.

PMID- 20697349
TI  - Transcriptional upregulation of histone deacetylase 2 promotes Myc-induced
      oncogenic effects.
AB  - Myc oncoproteins and histone deacetylases (HDACs) modulate gene transcription and
      enhance cancer cell proliferation, and HDAC inhibitors are among the most
      promising new classes of anticancer drugs. Here, we show that N-Myc and c-Myc
      upregulated HDAC2 gene expression in neuroblastoma and pancreatic cancer cells,
      respectively, which contributed to N-Myc- and c-Myc-induced cell proliferation.
      Cyclin G2 (CCNG2) was commonly repressed by N-Myc and HDAC2 in neuroblastoma
      cells and by c-Myc and HDAC2 in pancreatic cancer cells, and could be reactivated
      by HDAC inhibitors. 5-bromo-2'-deoxyuridine incorporation assays showed that
      transcriptional repression of CCNG2 was, in part, responsible for N-Myc-, c-Myc-
      and HDAC2-induced cell proliferation. Dual crosslinking chromatin
      immunoprecipitation assay demonstrated that N-Myc acted as a transrepressor by
      recruiting the HDAC2 protein to Sp1-binding sites at the CCNG2 gene core
      promoter. Moreover, HDAC2 was upregulated, and CCNG2 downregulated, in pre
      cancerous and neuroblastoma tissues from N-Myc transgenic mice, and c-Myc
      overexpression correlated with upregulation of HDAC2 and repression of CCNG2 in
      tumour tissues from pancreatic cancer patients. Taken together, our data indicate
      the critical roles of upregulation of HDAC2 and suppression of CCNG2 in Myc
      induced oncogenesis, and have significant implications for the application of
      HDAC inhibitors in the prevention and treatment of Myc-driven cancers.

PMID- 20697348
TI  - Analysis of the genome to personalize therapy for melanoma.
AB  - The treatment of cancer is being revolutionized by an improved understanding of
      the genetic events that occur in tumors. Advances in the understanding of the
      prevalence and patterns of mutations in melanoma have recently led to impressive
      results in trials of personalized, targeted therapies for this disease. In this
      review, we will discuss the molecular targets that have been validated
      clinically, additional genetic events that are candidates for future trials, and
      the challenges that remain to improve outcomes further in this aggressive
      disease.

PMID- 20697351
TI  - Regulation of the NRSF/REST gene by methylation and CREB affects the cellular
      phenotype of small-cell lung cancer.
AB  - The neuron-restrictive silencer factor/RE1-silencing transcription factor
      (NRSF/REST) is a negative regulator of gene expression restricting the expression
      of neuronal genes to the nervous system. NRSF/REST is highly expressed in non
      neuronal tissues like the lung. In previous work, we identified small-cell lung
      cancer (SCLC) cell lines with no detectable NRSF/REST expression that, as a
      consequence, expressed neuronal markers like L1-cell adhesion molecule (L1-CAM)
      and neural cell adhesion molecule (NCAM). The loss of NRSF/REST expression was
      linked to malignant progression; however, its mechanistic role remained elusive.
      Here, we show that NRSF/REST itself, rather than one of its regulated genes, acts
      like a classic tumour suppressor, being in part regulated by methylation. In
      SCLCs, NRSF/REST is positively regulated by CREB, with an NRSF/REST promoter
      fragment showing cell type specificity. Downstream, NRSF/REST directly regulates
      AKT2, in which NRSF/REST loss leads to an epidermal growth factor-mediated de
      regulation of AKT-Serine473 phosphorylation, important for cellular proliferation
      and survival. Assaying anchorage-independent growth, we observed that with
      reduced NRSF/REST expression, proliferation was significantly enhanced, whereas
      NRSF/REST rescue decreased the potential of cells to grow anchorage
      independently. Our observations support the fact that NRSF/REST may act as an
      important modulator of malignant progression in SCLC.

PMID- 20697350
TI  - The proximal signaling network of the BCR-ABL1 oncogene shows a modular
      organization.
AB  - BCR-ABL1 is a fusion tyrosine kinase, which causes multiple types of leukemia. We
      used an integrated proteomic approach that includes label-free quantitative
      protein complex and phosphorylation profiling by mass spectrometry to
      systematically characterize the proximal signaling network of this oncogenic
      kinase. The proximal BCR-ABL1 signaling network shows a modular and layered
      organization with an inner core of three leukemia transformation-relevant adaptor
      protein complexes (Grb2/Gab2/Shc1 complex, CrkI complex and Dok1/Dok2 complex).
      We introduced an 'interaction directionality' analysis, which annotates static
      protein networks with information on the directionality of phosphorylation
      dependent interactions. In this analysis, the observed network structure was
      consistent with a step-wise phosphorylation-dependent assembly of the
      Grb2/Gab2/Shc1 and the Dok1/Dok2 complexes on the BCR-ABL1 core. The CrkI complex
      demonstrated a different directionality, which supports a candidate assembly on
      the Nedd9 (Hef1, CasL) scaffold. As adaptor protein family members can compensate
      for each other in leukemic transformation, we compared members of the Dok and Crk
      protein families and found both overlapping and differential binding patterns. We
      identified an additional level of regulation for the CrkII protein via binding to
      14-3-3 proteins, which was independent from its inhibitory phosphorylation. We
      also identified novel components of the inner core complexes, including the
      kinases Pragmin (Sgk223) and Lrrk1 (Lrrk2 paralog). Pragmin was found as a
      component of the CrkI complex and is a potential link between BCR-ABL1/CrkI and
      RhoA signaling. Lrrk1 is an unusual kinase with a GTPase domain. We detected
      Lrrk1 as a component of the Grb2/Gab2/Shc1 complex and found that it functionally
      interacts with the regulator of small GTPases Arap1 (Centd2) and possibly
      participates in the mitogen-activated protein kinase response to cellular
      stresses. This modular and phosphorylation-driven interaction network provides a
      framework for the integration of pleiotropic signaling effects of BCR-ABL1 toward
      leukemic transformation.

PMID- 20697353
TI  - Id1 enhances RING1b E3 ubiquitin ligase activity through the Mel-18/Bmi-1
      polycomb group complex.
AB  - The helix-loop-helix inhibitor of differentiation and DNA binding (Id1) is well
      known as an oncogene in various tumors. Although it has been reported that Id1
      promotes several oncogenic processes, it is still unclear whether Id1 functions
      through epigenetic transcriptional regulation. In this study, we examined the
      effect of Id1 on polycomb group (PcG) proteins, which are crucial epigenetic gene
      silencers, and found that Id1 regulated the expression of Mel-18 and Bmi-1, both
      of which belong to polycomb repressive complex 1. We also confirmed that Id1
      induced Mel-18 downregulation, which was mediated by the Akt pathway, and
      consequently upregulated the transcription of its target gene, c-Myc. Using a
      promoter-reporter, we demonstrated that Id1 regulated Bmi-1 transcription through
      c-Myc binding to its E-box in the promoter. Finally, we examined the activity of
      E3 ligase RING1b, whose catalytic activity is increased by binding with the RING
      finger protein Bmi-1, and found that Id1 overexpression enhanced RING1b E3 ligase
      activity leading to accumulation of H2A ubiquitination and ubiquitin/proteasome
      mediated degradation of geminin. Taken together, our study provided a novel link
      between Id1 and PcG proteins and suggested that Id1 may contribute to tumor
      development through PcG-mediated epigenetic regulation.

PMID- 20697354
TI  - The protein kinase Pak4 disrupts mammary acinar architecture and promotes mammary
      tumorigenesis.
AB  - The Pak4 serine/threonine kinase is highly expressed in many cancer cell lines
      and human tumors. Although several studies have addressed the role for Pak4 in
      transformation of fibroblasts, most human cancers are epithelial in origin.
      Epithelial cancers are associated not only with changes in cell growth but also
      with changes in the cellular organization within the three-dimensional (3D)
      architecture of the affected tissues. In this study we used immortalized mouse
      mammary epithelial cells (iMMECs) as a model system to study the role for Pak4 in
      mammary tumorigenesis. iMMECs are an excellent model system for studying breast
      cancer, as they can grow in 3D-epithelial cell culture, in which they form acinar
      structures that recapitulate in vivo mammary morphogenesis. Although Pak4 is
      expressed at low levels in wild-type iMMECs, it is overexpressed in response to
      oncogenes, such as oncogenic Ras and Her2/neu. In this study we found that
      overexpression of Pak4 in iMMECs leads to changes in 3D acinar architecture that
      are consistent with oncogenic transformation. These include decreased central
      acinar cell death, abrogation of lumen formation, cell polarity alterations and
      deregulation of acinar size and cell number. Furthermore, iMMECs overexpressing
      Pak4 form tumors when implanted into the fat pads of athymic mice. Our results
      suggest that overexpression of Pak4 triggers events that are important for the
      transformation of mammary epithelial cells. This is likely to be owing to the
      ability of Pak4 to inhibit apoptosis and promote cell survival and thus
      subsequent uncontrolled proliferation, and to its ability to deregulate cell
      shape and polarity.

PMID- 20697355
TI  - The BRG1 ATPase of chromatin remodeling complexes is involved in modulation of
      mesenchymal stem cell senescence through RB-P53 pathways.
AB  - We focused our attention on brahma-related gene 1 (BRG1), the ATPase subunit of
      the SWItch/Sucrose NonFermentable (SWI/SNF) chromatin remodeling complex, and
      analyzed its role in mesenchymal stem cell (MSC) biology. We hypothesized that
      deviation from the correct concentration of these proteins, which act at the
      highest level of gene regulation, may be deleterious for cells. We wanted to know
      what would happen if a cell had to cope with altered regulation of gene
      expression, either by upregulation or downregulation of BRG1. We assumed that
      cells would try to restore homeostasis or, alternatively, that the event could
      trigger senescence/apoptosis phenomena. To this end, in MSCs, we silenced
      BRG1gene. Knockdown of BRG1 expression induced a significant increase in
      senescent cells and decrease in apoptotic cells. It is interesting that BRG1
      downregulation also induced an increase in heterochromatin. At the molecular
      level, these phenomena were associated with activation of retinoblastoma-like
      protein 2 (RB2)/P130- and P53-related pathways. Senescence was accompanied by
      reduced expression of some stemness-related genes. This is consistent with our
      previous research, which showed that BRG1 upregulation by ectopic expression also
      induced senescence processes. Together, these data suggest that BRG1 belongs to a
      class of genes whose expression is tightly regulated; hence, subtle alterations
      in BRG1 activity seem to negatively affect mechanisms regulating chromatin status
      and, in turn, impair cellular physiology.

PMID- 20697352
TI  - Binding of pro-prion to filamin A: by design or an unfortunate blunder.
AB  - Over the last decades, cancer research has focused on tumor suppressor genes and
      oncogenes. Genes in other cellular pathways has received less attention. Between
      0.5% to 1% of the mammalian genome encodes for proteins that are tethered on the
      cell membrane via a glycosylphosphatidylinositol (GPI)-anchor. The GPI
      modification pathway is complex and not completely understood. Prion (PrP), a GPI
      anchored protein, is infamous for being the only normal protein that when
      misfolded can cause and transmit a deadly disease. Though widely expressed and
      highly conserved, little is known about the functions of PrP. Pancreatic cancer
      and melanoma cell lines express PrP. However, in these cell lines the PrP exists
      as a pro-PrP as defined by retaining its GPI anchor peptide signal sequence (GPI
      PSS). Unexpectedly, the GPI-PSS of PrP has a filamin A (FLNA) binding motif and
      binds FLNA. FLNA is a cytolinker protein, and an integrator of cell mechanics and
      signaling. Binding of pro-PrP to FLNA disrupts the normal FLNA functions.
      Although normal pancreatic ductal cells lack PrP, about 40% of patients with
      pancreatic ductal cell adenocarcinoma express PrP in their cancers. These
      patients have significantly shorter survival time compared with patients whose
      cancers lack PrP. Pro-PrP is also detected in melanoma in situ but is
      undetectable in normal melanocyte, and invasive melanoma expresses more pro-PrP.
      In this review, we will discuss the underlying mechanisms by which binding of pro
      PrP to FLNA disrupts normal cellular physiology and contributes to tumorigenesis,
      and the potential mechanisms that cause the accumulation of pro-PrP in cancer
      cells.

PMID- 20697356
TI  - Transcriptional regulation of Wnt inhibitory factor-1 by Miz-1/c-Myc.
AB  - The Wnt signaling pathway is capable of self-regulation through positive and
      negative feedback mechanisms. For example, the oncoprotein c-Myc, which is
      upregulated by Wnt signaling activity, participates in a positive feedback loop
      of canonical Wnt signaling through repression of Wnt antagonists DKK1 and SFRP1.
      In this study, we investigated the mechanism of Wnt inhibitory factor-1 (WIF-1)
      silencing. Mapping of CpG island methylation of the WIF-1 promoter reveals
      regional methylation (-295 to -95 bp from the transcription start site) that
      correlates with transcriptional silencing. We identified Miz-1 as a direct
      activator of WIF-1 transcriptional activity, which is found at WIF-1 promoter. In
      addition, we show that c-Myc contributes to WIF-1 transcriptional repression in a
      Miz-1-dependent manner. Although the transient repression mediated by Miz-1/c-Myc
      is independent of de novo methylation, the stable repression by this complex is
      associated with CpG island methylation of the critical -295 to -95-bp region of
      the WIF-1 promoter. Importantly, Miz-1 and c-Myc are found at WIF-1 promoter in
      WIF-1 non-expressing cell lines DLD-1 and 209myc. Transient knockdown or somatic
      knockout of c-Myc in DLD-1 failed to restore WIF-1 expression suggesting that c
      Myc is involved in initiating rather than maintaining WIF-1 epigenetic silencing.
      In a genome-wide screen, DNAJA4, TGFbeta-induced and TRIM59 were repressed by c
      Myc overexpression and DNA promoter hypermethylation. Our data reveal novel
      insights into c-Myc-mediated DNA methylation-dependent transcriptional silencing,
      a mechanism that might contribute to the dysregulation of Wnt signaling in
      cancer.

PMID- 20697357
TI  - RhoA and RhoC are both required for the ROCK II-dependent promotion of centrosome
      duplication.
AB  - CDK2-cyclin E triggers centrosome duplication, and nucleophosmin (NPM/B23) is
      found to be one of its targets. NPM/B23 phosphorylated by CDK2-cyclin E acquires
      a high binding affinity to Rho-associated kinase (ROCK II), and physically
      associates with ROCK II. The NPM/B23-binding results in superactivation of ROCK
      II, which is a critical event for initiation of centrosome duplication. The
      activation of ROCK II also requires the binding of Rho small GTPase to the auto
      inhibitory region; hence the availability of the active Rho protein is an
      important aspect of the centrosomally localized ROCK II to properly initiate
      centrosome duplication. There are three isoforms of Rho (RhoA, B and C), all of
      which are capable of binding to and priming the activation of ROCK II. Here, we
      investigated which Rho isoform(s) are involved in the activation of ROCK II in
      respect to the initiation of centrosome duplication. We found that both RhoA and
      RhoC, but not RhoB, were required for initiation of centrosome duplication, and
      overactivation of RhoA, as well as RhoC, but not RhoB, promoted centrosome
      duplication and centrosome amplification.

PMID- 20697359
TI  - Regulation of MDM4 (MDMX) function by p76(MDM2): a new facet in the control of
      p53 activity.
AB  - Under basal growth conditions, p53 function is tightly controlled by the members
      of MDM family, MDM2 and MDM4. The Mdm2 gene codes, in addition to the full-length
      p90(MDM2), for a short protein, p76(MDM2) that lacks the p53-binding domain.
      Despite this property and at variance with p90(MDM2), this protein acts
      positively toward p53, although the molecular mechanism remains elusive. Here, we
      report that p76(MDM2) antagonizes MDM4 inhibitory function. We show that
      p76(MDM2) possesses intrinsic ubiquitinating and degrading activity, and through
      these activities controls MDM4 levels. Furthermore, the presence of p76(MDM2)
      decreases the association of MDM4 with p53 and p90(MDM2), and antagonizes p53
      degradation by the heterodimer MDM4/p90(MDM2). The p76(MDM2)-mediated regulation
      of MDM4 occurs in the cytoplasm, under basal growth conditions. Conversely, upon
      DNA damage, phosphorylation of MDM4Ser403 dissociates p76(MDM2) and prevents MDM4
      degradation. The overall negative control of MDM4 by p76(MDM2) reflects on p53
      function as p76(MDM2) impairs MDM4-mediated inhibition of p53 activity. In
      agreement with the positive role of p76(MDM2) toward p53, the p76(MDM2)/p90(MDM2)
      ratio significantly decreases in a group of thyroid tumor samples compared with
      normal counterparts. Overall, these findings reveal a new mechanism in the
      control of p53 basal activity that may account for the distinct sensitivity of
      tissues to stress signals depending on the balance among MDM proteins. Moreover,
      these data suggest an oncosuppressive function for a product of the Mdm2 gene.

PMID- 20697358
TI  - EMX2 is epigenetically silenced and suppresses growth in human lung cancer.
AB  - Lung cancer is a common cancer and the leading cause of cancer-related death
      worldwide. Aberrant activation of WNT signaling is implicated in lung
      carcinogenesis. EMX2, a human homologue of the Drosophila empty spiracles gene is
      a homeodomain-containing transcription factor. The function of EMX2 has been
      linked to the WNT signaling pathway during embryonic patterning in mice. However,
      little is known about the role of EMX2 in human tumorigenesis. In this study, we
      found that EMX2 was dramatically downregulated in lung cancer tissue samples and
      this downregulation was associated with methylation of the EMX2 promoter.
      Restoration of EMX2 expression in lung cancer cells lacking endogenous EMX2
      expression suppressed cell proliferation and invasive phenotypes, inhibited
      canonical WNT signaling, and sensitized lung cancer cells to the treatment of the
      chemo cytotoxic drug cisplatin. On the other hand, knockdown of EMX2 expression
      in lung cancer cells expressing endogenous EMX2 promoted cell proliferation,
      invasive phenotypes and canonical WNT signaling. Taken together, our study
      suggests that EMX2 may have important roles as a novel suppressor in human lung
      cancer.

PMID- 20697360
TI  - Evidence for a pro-apoptotic function of RACK1 in human breast cancer.

PMID- 20697361
TI  - Kidney cancer: A new nomogram predicting survival in renal cell carcinoma.

PMID- 20697363
TI  - Hematopoietic SCT for the treatment of multiple sclerosis.
AB  - Multiple sclerosis (MS) is the leading autoimmune indication for autologous
      hematopoietic SCT (aHSCT). Patient selection criteria and transplant
      interventions have been refined through a series of cohort and registry studies.
      High- and low-intensity chemotherapy-based conditioning regimens have been used,
      creating trade-offs between toxicity and effectiveness. TBI has been associated
      with greater toxicity and poor outcomes. aHSCT stops MS relapses and lessens the
      disability in malignant MS, which otherwise rapidly incapacitates patients.
      Better responses occur in progressive MS earlier in the disease when it has a
      more inflammatory nature. aHSCT prevents further disability in many patients, but
      some actually recover from their infirmities. Current regimens and supportive
      care result in very low morbidity and mortality. MS patients experience unique
      complications in addition to the expected toxicities. Cytokines used alone for
      stem-cell mobilization may induce MS flares but are safe to be used in
      combination with steroids or cytotoxic agents. Urinary tract infections, herpes
      virus reactivation and an engraftment syndrome may occur early after aHSCT.
      Rarely secondary autoimmune diseases have been reported late after HSCT.
      Increasing experience in caring for patients with MS has reduced the frequency
      and severity of toxicity. Conceived as an opportunity to 'reboot' a tolerant
      immune system, aHSCT is successful in treating patients with MS that is
      refractory to conventional immunomodulatory drugs.

PMID- 20697364
TI  - High-dose melphalan with or without stem cell support before myeloablative allo
      SCT for remission induction in patients with advanced relapsed or refractory AML.
AB  - Treatment strategies for relapsed/refractory AML are limited and disappointing.
      Recently, high-dose melphalan (HDM) chemotherapy and autologous hematopoietic SCT
      (HSCT) has been proposed for AML re-induction. We investigated the impact of HDM
      remission induction in highly advanced relapsed/refractory AML patients planned
      for allogeneic HSCT. A total of 23 patients with relapsed/refractory AML were
      prospectively scheduled for HDM with or without stem cell support followed by
      myeloablative allogeneic HSCT. Patients included nine individuals with a history
      of previous HSCT (seven allogeneic, two autologous). A total of 18 patients (78%)
      achieved a leukemia-free state and an additional four had substantial reduction
      of the initial leukemia burden warranting treatment continuation. There were no
      differences between patients with or without immediate stem cell support
      regarding mucositis or other organ toxicity. A total of 20 patients proceeded to
      myeloablative allogeneic HSCT. Outcome of allogeneic HSCT was poor: 11 patients
      (55%) relapsed, 7 patients (35%) died from TRM and only 2 patients (10%) were
      alive at the last follow-up. Our study shows that HDM is effective in inducing a
      leukemia-free state in patients with highly advanced relapsed/refractory AML.
      Leukemia burden reduction with HDM, however, did not translate into improved OS.

PMID- 20697362
TI  - Organ-sparing approaches for testicular masses.
AB  - Organ-sparing approaches are currently practiced in urology for many
      malignancies. Partial orchiectomy of germ cell tumors (GCT) provides potential
      benefits over radical surgery by reducing the need for androgen substitution,
      lessening psychological stress, and preserving fertility, with a durable cure
      rate. Furthermore, many testicular lesions detected clinically or by
      ultrasonography will be benign, in which case radical orchiectomy represents
      overtreatment. Partial orchiectomy for benign lesions allows preservation of
      endocrine and exocrine function, and reduced risk of local recurrence. However,
      selection criteria are not clear and one must always be suspicious that a GCT
      might exist. Carcinoma in situ that remains in the salvaged testicle is a
      challenge to treat. Radiation therapy is an option, although there is a high
      chance that patients will subsequently require hormonal replacement. Partial
      orchiectomy should be undertaken only in selected patients--men with bilateral
      testicular cancer or GCT in a solitary testis--if the size and location of the
      mass are amenable to surgery. Informed patient consent discussing radical
      orchiectomy as the gold standard is mandatory, and discussion of the risks
      associated with CIS and its treatment, as well as the need for androgen
      supplementation are paramount. Alternative strategies of organ preservation, such
      as radiotherapy, HIFU and chemotherapy, might be appropriate treatment options in
      the future. However, the safety and efficacy of these procedures needs to be
      demonstrated in comparison with partial orchiectomy in larger and prospective
      studies with longer follow-up.

PMID- 20697365
TI  - Successful tandem (autologous-cord blood) SCT in advanced neuroblastomas with
      highly amplified MYCN.
AB  - Although autologous tandem hematopoietic SCT has improved the prognosis of
      patients with advanced high-risk neuroblastoma, the results remain
      unsatisfactory. In an attempt to induce the graft-versus-tumor effect, we
      performed autologous PBSCT followed by allogeneic cord blood transplantation in
      three consecutive advanced neuroblastoma cases with marked BM infiltration and
      high MYCN amplification. Severe acute complications did not occur in any patient
      and they have maintained disease-free survival for 37-60 months. This strategy
      appears to be feasible and effective for the treatment of extremely high-risk
      neuroblastoma cases.

PMID- 20697366
TI  - Optimal timing of G-CSF administration for effective autologous stem cell
      collection.
AB  - The best time of G-CSF administration for PBPC collection remains to be defined.
      We aimed to identify optimal G-CSF administration timing for efficient autologous
      stem cell collection. A total of 262 lymphoma or multiple myeloma patients, who
      underwent PBPC collection from January 2000 to March 2008, were included. PBPCs
      were mobilized with chemotherapy followed by lenograstim at 10 MUg/kg/day.
      Patients received lenograstim at 2000 hours, about half a day before
      leukapheresis (PM group) before November 2004, and at 0600 hours, 3 h before
      apheresis (AM group) subsequently. In the AM group, the median number of total
      collected CD34+ cells/kg was greater over a shorter duration of apheresis, and
      the median number of collected CD34+ cells/kg at first leukapheresis was larger.
      Stem cell collection efficacy (ratio of total collected CD34+ cells/kg per number
      of leukapheresis procedures) was higher, and proportion of patients who yielded
      an optimum harvest was larger. The statistically significant between-group
      difference was observed only in patients with high-dose CY chemotherapy for stem
      cell mobilization in subgroup analysis. The present study showed that G-CSF
      injection 3 h before apheresis improved the efficacy of autologous stem cell
      collection.

PMID- 20697367
TI  - Early detection of relapse in patients with myelodysplastic syndrome after allo
      SCT.
AB  - Allo-SCT is the only potentially curative regimen for myelodysplastic syndromes
      (MDSs), but it is associated with a high relapse risk. The role of chimerism
      analysis for prediction of relapse is yet to be determined. To assess the
      clinical usefulness of mixed chimerism (MC) for predicting hematological relapse,
      75 consecutively transplanted patients with MDS were analyzed with regard to
      lineage-specific chimerism, encompassing CD33(+) cells in peripheral blood (PB,
      n=49) and CD34(+) cells in BM (n= 35). A cutoff of 5% recipient cells was used to
      discriminate complete donor chimerism from MC. A total of 19 patients (25%)
      experienced hematological relapse after a median of 5 (1-31) months. Sensitivity
      for detection of relapse was 59% for CD33(+) PB cells and 92% for CD34(+) BM
      cells with corresponding specificities of 91% and 65%. CD34(+) BM cells were
      analyzed before relapse in seven patients, five of whom showed MC at a median of
      2.5 (0.5-7) months before relapse. In contrast, 8 of 18 patients showed MC
      involving CD33 PB with a median of one month (0.5-2) before relapse. Here, we
      provide a model for early detection of relapse after SCT in MDS, in which serial
      characterization of both CD33(+) PB cells and CD34(+) BM cells gives an
      opportunity for early treatment before overt relapse.

PMID- 20697368
TI  - Double umbilical cord blood transplantation with reduced intensity conditioning
      and sirolimus-based GVHD prophylaxis.
AB  - The main limitations to umbilical cord blood (UCB) transplantation (UCBT) in
      adults are delayed engraftment, poor immunological reconstitution and high rates
      of non-relapse mortality (NRM). Double UCBT (DUCBT) has been used to circumvent
      the issue of low cell dose, but acute GVHD remains a significant problem. We
      describe our experience in 32 subjects, who underwent DUCBT after reduced
      intensity conditioning with fludarabine/melphalan/antithymocyte globulin and who
      received sirolimus and tacrolimus to prevent acute GVHD. Engraftment of
      neutrophils occurred in all patients at a median of 21 days, and platelet
      engraftment occurred at a median of 42 days. Three subjects had grade II-IV acute
      GVHD (9.4%) and chronic GVHD occurred in four subjects (cumulative incidence
      12.5%). No deaths were caused by GVHD and NRM at 100 days was 12.5%. At 2 years,
      NRM, PFS and OS were 34.4, 31.2 and 53.1%, respectively. As expected, immunologic
      reconstitution was slow, but PFS and OS were associated with reconstitution of
      CD4(+) and CD8(+) lymphocyte subsets, suggesting that recovery of adaptive
      immunity is required for the prevention of infection and relapse after
      transplantation. In summary, sirolimus and tacrolimus provide excellent GVHD
      prophylaxis in DUCBT, and this regimen is associated with low NRM after DUCBT.

PMID- 20697370
TI  - Mycobacterial diseases in pediatric hematopoietic SCT recipients.

PMID- 20697369
TI  - Clinical efficacy and safety of primary antifungal prophylaxis with posaconazole
      vs itraconazole in allogeneic blood and marrow transplantation.
AB  - Posaconazole has been recently approved for primary antifungal prophylaxis in
      patients with prolonged neutropenia after AML induction chemotherapy and patients
      with GVHD. We now present the first experience of the efficacy and safety of
      posaconazole during the early phase of post-allogeneic BMT (n=33; from June
      2007), in comparison with itraconazole primary prophylaxis (n=16; up to May
      2007). More patients receiving posaconazole were T-cell depleted (P=0.003).
      Groups were otherwise comparable in terms of age, sex, disease, neutrophil
      engraftment, incidence of GVHD, use of unrelated donors and type of conditioning.
      Safety data as well as the incidence of fever (84%) and persistent fever (27%)
      during the 100-day treatment period were comparable for both antifungal agents.
      Patients receiving posaconazole had a lower cumulative incidence of proven or
      probable invasive fungal disease, as defined by the European Organization for
      Research and Treatment of Cancer criteria (0 vs 12%; P=0.04), which associated
      with a higher probability of fungal-free survival (91 vs 56%; P=0.003) and an
      improved probability of OS (91 vs 63%; P=0.011) compared with patients receiving
      itraconazole. Our single-centre experience suggests that antifungal prophylaxis
      with posaconazole may lead to a better outcome than itraconazole for patients in
      the early high-risk neutropenic period after allogeneic BMT.

PMID- 20697371
TI  - Cyclosporine levels and rate of graft rejection following non-myeloablative
      conditioning for allogeneic hematopoietic SCT.
AB  - Hematopoietic SCT (HSCT) after non-myeloablative conditioning is associated with
      reduced TRM, and increased risk of graft rejection. Although preclinical data
      have shown the importance of post transplant immunosuppression in achieving
      engraftment, little is known about the role of CSA in the clinical setting of non
      myeloablative transplantation. In a retrospective analysis of patients treated
      with allogeneic HSCT after fludarabine and 2 Gy TBI, 15 of 77 evaluable patients
      (20%) experienced primary (n=2) or secondary graft rejection at a median of 66
      days post transplant. Mean day 1-28 CSA trough levels were inversely associated
      with day 28 chimerism (median 99, 85 and 70% for mean CSA <300, 300-600 and >600
      ng/mL, respectively; P=0.003). A similar association was observed for the
      cumulative incidence of graft rejection, which occurred in 8% (<300 ng/mL), 26%
      (300-600 ng/mL) and 50% (>600 ng/mL, P=0.005) of patients. The detrimental effect
      of high CSA levels on engraftment was confirmed in multivariable models and was
      found to operate comparably in sibling and unrelated donor transplants.
      Impairment of donor T-cell function by high serum levels of CSA might account for
      this finding, which should be verified in a larger patient group to better
      understand the role of CSA in non-myeloablative transplantation.

PMID- 20697372
TI  - Early clinical indicators of transplant-associated thrombotic microangiopathy in
      pediatric neuroblastoma patients undergoing auto-SCT.
AB  - Patients undergoing auto-SCT for neuroblastoma present a unique population to
      study transplant-associated thrombotic microangiopathy (TA-TMA), due to
      standardized chemotherapy and later exposure to radiation and cis-retinoic acid
      (cis-RA). We retrospectively analyzed 20 patients after auto-SCT to evaluate
      early clinical indicators of TA-TMA. A total of 6 patients developing TA-TMA (30%
      prevalence) were compared with 14 controls. Four of six patients were diagnosed
      with TA-TMA by 25 days after auto-SCT. Compared with controls, TA-TMA patients
      had higher average systolic and diastolic blood pressure levels during high-dose
      chemotherapy and developed hypertension by day 13 after auto-SCT. Proteinuria was
      a significant marker for TA-TMA, whereas blood and platelet transfusion
      requirements were not. Serum creatinine did not differ between groups post
      transplant. However, patients with TA-TMA had a 60% decrease in renal function
      from baseline by nuclear glomerular filtration rate, compared with a 25% decrease
      in those without TA-TMA (P=0.001). There was no TA-TMA-related mortality.
      Significant complications included end-stage renal disease (n=1) and
      polyserositis (n=3). Patients with TA-TMA were unable to complete cis-RA therapy
      after auto-SCT. We suggest that careful attention to blood pressure and
      urinalysis will assist in the early diagnosis of TA-TMA, whereas serum creatinine
      seems to be an insensitive marker for this condition.

PMID- 20697374
TI  - Cytokines induce small intestine and liver injury after renal ischemia or
      nephrectomy.
AB  - Patients with acute kidney injury (AKI) frequently suffer from extra-renal
      complications including hepatic dysfunction and systemic inflammation. We aimed
      to determine the mechanisms of AKI-induced hepatic dysfunction and systemic
      inflammation. Mice subjected to AKI (renal ischemia reperfusion (IR) or
      nephrectomy) rapidly developed acute hepatic dysfunction and suffered
      significantly worse hepatic IR injury. After AKI, rapid peri-portal hepatocyte
      necrosis, vacuolization, neutrophil infiltration and pro-inflammatory mRNA
      upregulation were observed suggesting an intestinal source of hepatic injury.
      Small intestine histology after AKI showed profound villous lacteal capillary
      endothelial apoptosis, disruption of vascular permeability and epithelial
      necrosis. After ischemic or non-ischemic AKI, plasma TNF-alpha, IL-17A and IL-6
      increased significantly. Small intestine appears to be the source of IL-17A, as
      IL-17A levels were higher in the portal circulation and small intestine compared
      with the levels measured from the systemic circulation and liver. Wild-type mice
      treated with neutralizing antibodies against TNF-alpha, IL-17A or IL-6 or mice
      deficient in TNF-alpha, IL-17A, IL-17A receptor or IL-6 were protected against
      hepatic and small intestine injury because of ischemic or non-ischemic AKI. For
      the first time, we implicate the increased release of IL-17A from small intestine
      together with induction of TNF-alpha and IL-6 as a cause of small intestine and
      liver injury after ischemic or non-ischemic AKI. Modulation of the inflammatory
      response and cytokine release in the small intestine after AKI may have important
      therapeutic implications in reducing complications arising from AKI.

PMID- 20697373
TI  - Gene delivery of TGF-beta1 induces arthrofibrosis and chondrometaplasia of
      synovium in vivo.
AB  - To understand the cellular and molecular events contributing to arthrofibrosis,
      we used an adenovirus to deliver and overexpress transforming growth factor-beta
      1 (TGF-beta1) cDNA (Ad.TGF-beta1) in the knee joints of immunocompromised rats.
      Following delivery, animals were killed periodically, and joint tissues were
      examined macroscopically and histologically. PCR-array was used to assay
      alterations in expression patterns of extracellular matrix (ECM)-associated
      genes. By days 5 and 10, TGF-beta1 induced an increase in knee diameter and
      complete encasement of joints in dense scar-like tissue, locking joints at 90
      degrees  of flexion. Histologically, massive proliferation of synovial
      fibroblasts was seen, followed by their differentiation into myofibroblasts. The
      fibrotic tissue displaced the normal architecture of the joint capsule and fused
      with articular cartilage. RNA expression profiles showed high levels of
      transcription of numerous MMPs, matricellular and ECM proteins. By day 30, the
      phenotype of the fibrotic tissue had undergone chondrometaplasia, indicated by
      cellular morphology, matrix composition and >100-fold increases in expression of
      collagen type II and cartilage link protein. Pre-labeling of articular cells by
      injection with recombinant lentivirus containing eGFP cDNA showed
      fibrotic/cartilaginous tissues appeared to arise almost entirely from local
      proliferation and differentiation of resident fibroblasts. Altogether, these
      results indicate that TGF-beta1 is a potent inducer of arthrofibrosis, and
      illustrate the proliferative potential and plasticity of articular fibroblasts.
      They suggest the mechanisms causing arthrofibrosis share many aspects with
      tumorigenesis.

PMID- 20697375
TI  - Enumeration of islets by nuclei counting and light microscopic analysis.
AB  - Islet enumeration in impure preparations by conventional dithizone staining and
      visual counting is inaccurate and operator dependent. We examined nuclei counting
      for measuring the total number of cells in islet preparations, and we combined it
      with morphological analysis by light microscopy (LM) for estimating the volume
      fraction of islets in impure preparations. Cells and islets were disrupted with
      lysis solution and shear, and accuracy of counting successively diluted nuclei
      suspensions was verified with (1) visual counting in a hemocytometer after
      staining with crystal violet, and automatic counting by (2) aperture electrical
      resistance measurement and (3) flow cytometer measurement after staining with 7
      aminoactinomycin-D. DNA content averaged 6.5 and 6.9 pg of DNA per cell for rat
      and human islets, respectively, in agreement with literature estimates. With pure
      rat islet preparations, precision improved with increasing counts, and samples
      with about >=160 islets provided a coefficient of variation of about 6%. Aliquots
      of human islet preparations were processed for LM analysis by stereological point
      counting. Total nuclei counts and islet volume fraction from LM analysis were
      combined to obtain the number of islet equivalents (IEs). Total number of IE by
      the standard method of dithizone staining/manual counting was overestimated by
      about 90% compared with LM/nuclei counting for 12 freshly isolated human islet
      research preparations. Nuclei counting combined with islet volume fraction
      measurements from LM is a novel method for achieving accurate islet enumeration.

PMID- 20697376
TI  - Viral factors induce Hedgehog pathway activation in humans with viral hepatitis,
      cirrhosis, and hepatocellular carcinoma.
AB  - Hedgehog (Hh) pathway activation promotes many processes that occur during
      fibrogenic liver repair. Whether the Hh pathway modulates the outcomes of virally
      mediated liver injury has never been examined. Gene-profiling studies of human
      hepatocellular carcinomas (HCCs) demonstrate Hh pathway activation in HCCs
      related to chronic infection with hepatitis B virus (HBV) or hepatitis C virus
      (HCV). Because most HCCs develop in cirrhotic livers, we hypothesized that Hh
      pathway activation occurs during fibrogenic repair of liver damage due to chronic
      viral hepatitis, and that Hh-responsive cells mediate disease progression and
      hepatocarciongenesis in chronic viral hepatitis. Immunohistochemistry and qRT-PCR
      analysis were used to analyze Hh pathway activation and identify Hh-responsive
      cell types in liver biopsies from 45 patients with chronic HBV or HCV. Hh
      signaling was then manipulated in cultured liver cells to directly assess the
      impact of Hh activity in relevant cell types. We found increased hepatic
      expression of Hh ligands in all patients with chronic viral hepatitis, and
      demonstrated that infection with HCV stimulated cultured hepatocytes to produce
      Hh ligands. The major cell populations that expanded during cirrhosis and HCC
      (ie, liver myofibroblasts, activated endothelial cells, and progenitors
      expressing markers of tumor stem/initiating cells) were Hh responsive, and higher
      levels of Hh pathway activity associated with cirrhosis and HCC. Inhibiting
      pathway activity in Hh-responsive target cells reduced fibrogenesis,
      angiogenesis, and growth. In conclusion, HBV/HCV infection increases hepatocyte
      production of Hh ligands and expands the types of Hh-responsive cells that
      promote liver fibrosis and cancer.

PMID- 20697377
TI  - Monocyte chemoattractant protein-1 deficiency does not affect steatosis or
      inflammation in livers of mice fed a methionine-choline-deficient diet.
AB  - Monocyte chemoattractant protein-1 (MCP-1, Ccl2) expression is increased in
      livers of patients with nonalcoholic steatohepatitis and in murine models of
      steatohepatitis. Several studies in rodents indicate that MCP-1 contributes to
      liver steatosis induced by feeding a high-fat diet. However, the extent of MCP-1
      involvement in the widely utilized methionine-choline-deficient (MCD) diet model
      of steatohepatitis has not been determined. We tested the hypothesis that MCP-1
      contributes to steatohepatitis in mice fed the MCD diet. MCP-1-deficient mice on
      a C57Bl/6J background and age-matched C57Bl/6J mice were fed either MCD diet or
      control diet for 4 weeks. MCP-1 deficiency did not affect steatohepatitis, as
      indicated by liver histopathology, nor did it affect serum alanine
      aminotransferase activity, hepatic triglyceride levels, hepatic inflammatory gene
      induction, or macrophage accumulation in mice fed the MCD diet. MCP-1 deficiency
      reduced the expression of the profibrogenic genes, pro-collagen 1a1, connective
      tissue growth factor, and transforming growth factor-beta, in mice fed the MCD
      diet. MCP-1 deficiency significantly reduced collagen deposition and alpha-smooth
      muscle actin protein levels in the livers of mice fed the MCD diet. The results
      indicate that MCP-1 does not contribute to liver steatosis or inflammation in the
      MCD diet model of steatohepatitis. Rather, the data suggest that MCP-1
      contributes to fibrosis in mice fed the MCD diet, independent of effects on
      steatosis and inflammation.

PMID- 20697378
TI  - Quantitative analysis of cell composition and purity of human pancreatic islet
      preparations.
AB  - Despite improvements in outcomes for human islet transplantation,
      characterization of islet preparations remains poorly defined. This study used
      both light microscopy (LM) and electron microscopy (EM) to characterize 33 islet
      preparations used for clinical transplants. EM allowed an accurate identification
      and quantification of cell types with measured cell number fractions (mean+/
      s.e.m.) of 35.6+/-2.1% beta-cells, 12.6+/-1.0% non-beta-islet cells (48.3+/-2.6%
      total islet cells), 22.7+/-1.5% duct cells, and 25.3+/-1.8% acinar cells. Of the
      islet cells, 73.6+/-1.7% were beta-cells. For comparison with the literature,
      estimates of cell number fraction, cell volume, and extracellular volume were
      combined to convert number fraction data to volume fractions applicable to cells,
      islets, and the entire preparation. The mathematical framework for this
      conversion was developed. By volume, beta-cells were 86.5+/-1.1% of the total
      islet cell volume and 61.2+/-0.8% of intact islets (including the extracellular
      volume), which is similar to that of islets in the pancreas. Our estimates
      produced 1560+/-20 cells in an islet equivalent (volume of 150-MUm diameter
      sphere), of which 1140+/-15 were beta-cells. To test whether LM analysis of the
      same tissue samples could provide reasonable estimates of purity of the islet
      preparations, volume fraction of the islet tissue was measured on thin sections
      available from 27 of the clinical preparations by point counting morphometrics.
      Islet purity (islet volume fraction) of individual preparations determined by LM
      and EM analyses correlated linearly with excellent agreement (R2=0.95). However,
      islet purity by conventional dithizone staining was substantially higher with a
      20-30% overestimation. Thus, both EM and LM provide accurate methods to determine
      the cell composition of human islet preparations and can help us understand many
      of the discrepancies of islet composition in the literature.

PMID- 20697380
TI  - Establishment of a standard 14-3-3 protein assay of cerebrospinal fluid as a
      diagnostic tool for Creutzfeldt-Jakob disease.
AB  - Periodic sharp wave complexes observed on an electroencephalographic recording
      and the presence of a 14-3-3 protein in the cerebrospinal fluid (CSF) are both
      included in the diagnostic criteria for the Creutzfeldt-Jakob disease (CJD)
      supplied by the World Health Organization; however, the presence or absence of
      the 14-3-3 protein in the CSF is sometimes difficult to discern on a western blot
      because of equivocal bands. The goal of this study was to establish a standard 14
      3-3 protein assay and to determine the threshold level of a 14-3-3 protein that
      can be assayed by western blot. We searched for the most suitable isoform of the
      14-3-3 protein to test for in protein assays, and the most sensitive antibody
      among four antibodies with an affinity for 14-3-3. We measured the levels of all
      14-3-3 isoforms in 112 patients with CJD and in 100 patients with other diseases.
      We compared the performances of four different antibodies. We carried out a semi
      quantitative analysis of gamma-isoform levels using the LAS 3000 system, which
      was capable of producing a digital image from the luminescence on a western blot.
      We determined that the most suitable isoform of the 14-3-3 protein for conducting
      a standardized assay was the gamma-isoform. Among the four commercially available
      antibodies for this protein, the most sensitive and specific was 18647 (IBL,
      Japan). We report the high repeatability of the detection of the 14-3-3 protein
      by this antibody to the gamma-isoform, showing that western blot can be used for
      semi-quantitative analysis.

PMID- 20697381
TI  - MAQC-II: analyze that!

PMID- 20697379
TI  - Development of thyroid gland and ultimobranchial body cyst is independent of p63.
AB  - The ultimobranchial body (UBB) and thyroid primordium are the origins of the
      thyroid gland that fuse around embryonic day 14.5 of mouse gestation, ultimately
      giving rise to calcitonin-producing C cells and thyroglobulin-producing
      follicular cells, respectively. A homeodomain transcription factor NKX2-1 is
      expressed both in the UBB and the thyroid primordium, and is critical for
      development of the thyroid gland. In this study, the role of p63 in development
      of UBB and the thyroid gland was analyzed by histological, immunohistochemical,
      and electron microscopic analyses using mice with various combinations of Nkx2-1
      and p63 wild-type, heterozygous, and null alleles. In the absence of p63, a
      normal thyroid gland develops, as revealed by expression of thyroglobulin and
      calcitonin, thus showing that p63 is not required for thyroid development.
      However, in mice carrying the Nkx2-1-null allele, the UBB remains as a cystic
      vesicular structure and/or in nested patterns consisting of p63-positive cells
      surrounding the vesicle and undifferentiated immature cells with occasional cilia
      lying inside. The cystic UBB was present even in the Nkx2-1;p63 double-null mice.
      The structure and p63 expression pattern of the UBB cyst strikingly resemble the
      solid cell nest. These results show that in the absence of NKX2-1, UBB becomes
      cystic independent of p63, which is likely the origin of SCN.

PMID- 20697382
TI  - Wrong numbers?

PMID- 20697383
TI  - Industry makes strides in melanoma.

PMID- 20697384
TI  - Firms combine experimental cancer drugs to speed development.

PMID- 20697386
TI  - FDA transparency rules could hit small companies hardest.

PMID- 20697388
TI  - Food firms test fry Pioneer's trans fat-free soybean oil.

PMID- 20697393
TI  - 2Q10-spreading the wealth.

PMID- 20697394
TI  - Drugmakers dance with autism.

PMID- 20697395
TI  - Waking up and smelling the coffee.

PMID- 20697396
TI  - Genetic stability in two commercialized transgenic lines (MON810).

PMID- 20697398
TI  - Distances needed to limit cross-fertilization between GM and conventional maize
      in Europe.

PMID- 20697399
TI  - Case study: India's billion dollar biotech.

PMID- 20697400
TI  - DNA patents and diagnostics: not a pretty picture.

PMID- 20697401
TI  - Public biotech 2009-the numbers.

PMID- 20697402
TI  - Bilski v. Kappos: the US Supreme Court broadens patent subject-matter
      eligibility.

PMID- 20697404
TI  - Can HIV be cured with stem cell therapy?

PMID- 20697405
TI  - Microarrays in the clinic.

PMID- 20697406
TI  - Shaking up genome engineering.

PMID- 20697407
TI  - The expanding family of dendritic cell subsets.

PMID- 20697411
TI  - Salt, aldosterone, and insulin resistance: impact on the cardiovascular system.
AB  - Hypertension and type 2 diabetes mellitus (T2DM) are powerful risk factors for
      cardiovascular disease (CVD) and chronic kidney disease (CKD), both of which are
      leading causes of morbidity and mortality worldwide. Research into the
      pathophysiology of CVD and CKD risk factors has identified salt sensitivity and
      insulin resistance as key elements underlying the relationship between
      hypertension and T2DM. Excess dietary salt and caloric intake, as commonly found
      in westernized diets, is linked not only to increased blood pressure, but also to
      defective insulin sensitivity and impaired glucose homeostasis. In this setting,
      activation of the sympathetic nervous system and the renin-angiotensin
      aldosterone system (RAAS), as well as increased signaling through the
      mineralocorticoid receptor (MR), result in increased production of reactive
      oxygen species and oxidative stress, which in turn contribute to insulin
      resistance and impaired vascular function. In addition, insulin resistance is not
      limited to classic insulin-sensitive tissues such as skeletal muscle, but it also
      affects the cardiovascular system, where it participates in the development of
      CVD and CKD. Current clinical knowledge points towards an impact of salt
      restriction, RAAS blockade, and MR antagonism on cardiovascular and renal
      protection, but also on improved insulin sensitivity and glucose homeostasis.

PMID- 20697413
TI  - Inequalities in cancer survival and the NHS cancer plan: evidence of progress?

PMID- 20697414
TI  - Temporal analysis of mechanisms leading to stimulation of glucose uptake in
      skeletal muscle cells by an adipokine mixture derived from primary rat
      adipocytes.
AB  - OBJECTIVE: The direct effects of adipokines on skeletal muscle metabolism have
      been well established. As the combinatorial effects of adipokine mixtures are
      likely to be of more physiological relevance, we used a coculture system of
      primary rat adipocytes and L6 skeletal muscle cells to examine the effects of
      adiponectin derived from primary rat adipocytes on rat skeletal muscle cells.
      RESULTS: We showed that coculture with adipocytes stimulated glucose uptake in L6
      cells within 30  min and this correlated with an increase of glucose transporter
      isoform 4 (GLUT4) localization to the plasma membrane. These effects were
      dependent on the reorganization of the actin cytoskeleton, demonstrated by
      rhodamine-labeled phalloidin immunofluorescence, as cytochalasin D attenuated the
      glucose uptake induced by adipocyte-conditioned media. Temporal analysis revealed
      that enhanced glucose uptake was maintained after 24  h of coculture, and this
      was attributed to an increase in both GLUT1 expression and the cell surface
      content of GLUT4. We established a role for adiponectin in mediating these
      effects as antibody-mediated neutralization attenuated the metabolic effects of
      adipocyte-conditioned media. Furthermore, compound C blocked these effects,
      suggesting an important role for AMPK. Importantly, when we compared the effects
      of full-length recombinant adiponectin with adipocyte-conditioned media, we
      confirmed that recombinant adiponectin was unable to stimulate glucose uptake in
      L6 cells despite having an important role in adipocyte-conditioned media.
      CONCLUSIONS: Our results demonstrate the importance of examining the effects of
      adipokines in the context of physiologically relevant mixtures to accurately
      determine their metabolic effects on skeletal muscle.

PMID- 20697412
TI  - Imaging the right ventricle--current state of the art.
AB  - The right ventricle has long been the 'forgotten ventricle', as it is difficult
      to image owing to its complex morphology, its thin wall with coarse
      trabeculations, and its anterior position within the chest. Developments in
      cardiac magnetic resonance imaging (CMR) and echocardiography have provided new
      insights into right ventricular (RV) structure and function. RV performance seems
      to be an important determinant of clinical status and long-term outcome in
      patients with pulmonary hypertension, cardiomyopathies, and, especially, in
      patients with congenital heart disease. A variety of different parameters can be
      measured to assess RV function, but a lot of uncertainty remains on how to assess
      RV performance in daily clinical practice and which measurements to use in
      clinical decision-making. CMR is currently considered the reference technique for
      RV volumetry and calculation of ejection fraction. Various echocardiographic
      techniques can provide reliable information on RV dimensions and RV systolic and
      diastolic function that can be used in clinical follow-up. The introduction of
      newer echocardiographic techniques, such as three-dimensional echocardiography,
      tissue Doppler ultrasonography, and ultrasound strain imaging, challenge the
      leading role of CMR in RV functional assessment, but further validation and
      accumulation of data are required before these techniques can play a key part in
      clinical decision-making.

PMID- 20697415
TI  - ALOX12 polymorphisms are associated with fat mass but not peak bone mineral
      density in Chinese nuclear families.
AB  - OBJECTIVE: Arachidonate 12-lipoxygenase (ALOX12) is a member of the lipoxygenase
      superfamily, which catalyzes the incorporation of molecular oxygen into
      polyunsaturated fatty acids. The products of ALOX12 reactions serve as endogenous
      ligands for peroxisome proliferator-activated receptor gamma (PPARG). The
      activation of the PPARG pathway in marrow-derived mesenchymal progenitors
      stimulates adipogenesis and inhibits osteoblastogenesis. Our objective was to
      determine whether polymorphisms in the ALOX12 gene were associated with
      variations in peak bone mineral density (BMD) and obesity phenotypes in young
      Chinese men. METHODS: All six tagging single-nucleotide polymorphisms (SNPs) in
      the ALOX12 gene were genotyped in a total of 1215 subjects from 400 Chinese
      nuclear families by allele-specific polymerase chain reaction. The BMD at the
      lumbar spine and hip, total fat mass (TFM) and total lean mass (TLM) were
      measured using dual-energy X-ray absorptiometry. The pairwise linkage
      disequilibrium among SNPs was measured, and the haplotype blocks were inferred.
      Both the individual SNP markers and the haplotypes were tested for an association
      with the peak BMD, body mass index, TFM, TLM and percentage fat mass (PFM) using
      the quantitative transmission disequilibrium test (QTDT). RESULTS: Using the
      QTDT, significant within-family association was found between the rs2073438
      polymorphism in the ALOX12 gene and the TFM and PFM (P=0.007 and 0.012,
      respectively). Haplotype analyses were combined with our individual SNP results
      and remained significant even after correction for multiple testing. However, we
      failed to find significant within-family associations between ALOX12 SNPs and the
      BMD at any bone site in young Chinese men. CONCLUSIONS: Our present results
      suggest that the rs2073438 polymorphism of ALOX12 contributes to the variation of
      obesity phenotypes in young Chinese men, although we failed to replicate the
      association with the peak BMD variation in this sample. Further independent
      studies are needed to confirm our findings.

PMID- 20697416
TI  - Studies on the antiobesity effect of zinc-alpha2-glycoprotein in the ob/ob mouse.
AB  - OBJECTIVE: To investigate the mechanism of the lipid depletion by zinc-alpha(2)
      glycoprotein (ZAG). DESIGN: Studies were conducted in the ob/ob mouse, or on
      isolated adipocytes from these animals or their lean counterparts. RESULTS:
      Treatment of these animals for 15 days with ZAG (100  MUg, intravenously, daily)
      resulted in a reduction of body weight of 6.55  g compared with phosphate
      buffered saline-treated controls, without a change in food or water intake, but
      with a 0.4  degrees C rise in rectal temperature. ZAG-treated mice had a 30%
      reduction in carcass fat mass and a twofold increase in weight of brown adipose
      tissue. Epididymal adipocytes from ZAG-treated mice showed an increased
      expression of ZAG and hormone-sensitive lipase (HSL), and this was maintained for
      a further 3 days in the absence of ZAG. There was an increased lipolytic response
      to isoproterenol, which was retained for 3 days in vitro in the absence of ZAG.
      Expression of HSL was also increased in subcutaneous and visceral adipose tissue,
      as was also adipose triglyceride lipase (ATGL). There was a rapid loss of
      labelled lipid from epididymal adipose tissue of ZAG-treated mice, but not from
      the other depots, reflecting the difference in sensitivity to lipolytic stimuli.
      The increased expression of HSL and ATGL may involve the extracellular signal
      regulated kinase (ERK) pathway, as the active (phospho) form was upregulated in
      all adipose depots after ZAG administration, whereas in vitro studies showed
      induction of HSL and ATGL by ZAG to be attenuated by PD98059, an inhibitor of the
      ERK pathway. CONCLUSION: These results suggest that ZAG not only induces direct
      lipolysis, but also sensitizes adipose tissue to other lipolytic stimuli.

PMID- 20697417
TI  - The 'Healthy Dads, Healthy Kids' randomized controlled trial: efficacy of a
      healthy lifestyle program for overweight fathers and their children.
AB  - OBJECTIVE: To evaluate the feasibility and efficacy of the 'Healthy Dads, Healthy
      Kids' (HDHK) program, which was designed to help overweight fathers lose weight
      and be a role model of positive health behaviors for their children. DESIGN:
      Randomized controlled trial. PARTICIPANTS: A total of 53 overweight/obese men
      (mean (s.d.) age=40.6 (7.1) years; body mass index (BMI)=33.2 (3.9)) and their
      primary school-aged children (n=71, 54% boys; mean (s.d.) age=8.2 (2.0) years)
      were randomly assigned (family unit) to either (i) the HDHK program (n=27
      fathers, n=39 children) or (ii) a wait-list control group (n=26 fathers, n=32
      children). INTERVENTION: Fathers in the 3-month program attended eight face-to
      face education sessions. Children attended three of these sessions. OUTCOMES: The
      primary outcome was fathers' weight. Fathers and their children were assessed at
      baseline, and at 3- and 6-month follow-up, for weight, waist circumference, BMI,
      blood pressure, resting heart rate (RHR), objectively measured physical activity
      and self-reported dietary intake. RESULTS: Intention-to-treat analysis revealed
      significant between-group differences at 6 months for weight loss (P<0.001), with
      HDHK fathers losing more weight (-7.6  kg; 95% confidence interval (CI) -9.2, 
      6.0; d=0.54) than control group fathers (0.0  kg; 95% CI -1.4, 1.6). Significant
      treatment effects (P<0.05) were also found for waist circumference (d=0.62), BMI
      (d=0.53), systolic blood pressure (d=0.92), RHR (d=0.66) and physical activity
      (d=0.91), but not for dietary intake. In children, significant treatment effects
      (P<0.05) were found for physical activity (d=0.74), RHR (d=0.51) and dietary
      intake (d=0.84). CONCLUSION: The HDHK program resulted in significant weight loss
      and improved health-related outcomes in fathers and improved eating and physical
      activity among children. Targeting fathers is a novel and efficacious approach to
      improving health behavior in their children.

PMID- 20697418
TI  - A classification and regression tree to assist clinical decision making in airway
      management for patients with cervical spinal cord injury.
AB  - STUDY DESIGN: This was a prospective observational study. OBJECTIVES: To review
      airway management of patients with acute cervical spinal cord injury (CSCI) who
      are admitted to the intensive care unit (ICU) and to develop a classification and
      regression tree (CART) to direct clinical decision making in airway management.
      SETTING: This study was carried out in Australia. METHODS: All patients with CSCI
      who required intubation and mechanical ventilation and who were admitted to ICU
      in three tertiary hospitals in Melbourne between October 2004 and May 2009 and
      two other interstate hospitals between December 2004 and December 2005 were
      included. Airway management was recorded. RESULTS: A total of 114 patients were
      included. Tracheostomy insertion occurred in 68 patients (59.7%). Using CART
      analysis, it was found that the variables forced vital capacity, the volume of
      pulmonary secretion and gas exchange were predictive of airway management on
      82.3% occasions with an 8.7% extubation failure rate. CONCLUSION: A CART can be
      useful in clinical decision making regarding airway management in CSCI.

PMID- 20697419
TI  - Incidence of symptomatic autonomic dysreflexia varies according to the bowel and
      bladder management techniques in patients with spinal cord injury.
AB  - STUDY DESIGN: A retrospective, multicenter study. OBJECTIVES: To investigate the
      relationship between bowel and bladder management methods and symptomatic
      autonomic dysreflexia (AD) during hospitalization in patients with spinal cord
      injury (SCI). SETTING: Twenty-eight Rosai hospitals in Japan. METHODS: The study
      subjects were 571 patients with SCI who had been admitted to 28 Rosai hospitals
      between April 1997 and March 2007 for rehabilitation therapy and fulfilled the
      following criteria: (1) SCI at or above sixth thoracic level, (2) discharged from
      hospital after more than 4 months of admission for initial injury and (3) lack of
      pressure ulcers, deep venous thrombosis, ureteral and renal stones or heterotopic
      ossification throughout hospitalization to exclude possible influence of these
      complications on cardiovascular reflexes. The study subjects were examined for
      the incidence of symptomatic AD according to age, sex, ASIA Impairment Scale,
      injury level, bowel and bladder management techniques at discharge. RESULTS: The
      Rosai Hospital registry included 3006 persons with SCI during 1997-2007, and 571
      patients fulfilled the above criteria. The highest incidence of symptomatic AD
      was diagnosed in subjects using reflex voiding and in those using manual removal
      of stool. By contrast, the lowest incidence of symptomatic AD was in those on
      continent spontaneous voiding and continent spontaneous defecation. CONCLUSION:
      Medical staff should evaluate the presence of AD in patients with SCI at or above
      the T6 level under bladder and bowel management such as reflex voiding and manual
      removal of stool.

PMID- 20697420
TI  - Independent spinal cord atrophy measures correlate to motor and sensory deficits
      in individuals with spinal cord injury.
AB  - STUDY DESIGN: Cross-sectional descriptive analysis of magnetic resonance imaging
      (MRI) and clinical outcome. OBJECTIVES: The aim of this study was to present
      anatomically consistent and independent spinal cord atrophy measures based on
      standard MRI material and analyze their specific relations to sensory and motor
      outcome in individuals with chronic incomplete spinal cord injury (SCI). SETTING:
      Danish study on human SCI. METHODS: We included 19 individuals with chronic
      incomplete SCI and 16 healthy controls. Participants underwent MRI and a
      neurological examination including sensory testing for light touch and pinprick,
      and muscle strength. Antero-posterior width (APW), left-right width (LRW) and
      cross-sectional spinal cord area (SCA) were extracted from MRI at the spinal
      level of C2. The angular variation of the spinal cord radius over the full circle
      was also extracted and compared with the clinical scores. RESULTS: The motor
      score was correlated to LRW and the sensory scores were correlated to APW. The
      scores correlated also well with decreases in spinal cord radius in oblique
      angles in coherent and non-overlapping sectors for the sensory and motor
      qualities respectively. CONCLUSION: APW and LRW can be used to assess sensory and
      motor function independently. The finding is corresponding well with the
      respective locations of the main sensory and motor pathways.

PMID- 20697421
TI  - Functional outcome and discharge destination in elderly patients with spinal cord
      injuries.
AB  - STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To describe functional
      outcome and discharge destination of elderly patients with traumatic spinal cord
      injuries. SETTING: National Spinal Injuries Unit, Glasgow, UK. METHODS: We
      collected data for 5 years on all patients >65 years old with a traumatic spinal
      cord injury treated at the National Spinal Injuries Unit. RESULTS: We identified
      39 patients. Of these, nine patients died during admission; all had cervical
      spine injuries. The mean age of the 30 survivors was 73 years (range 65-88). The
      most common cause of injury was a fall: 26 patients (87%). In addition, 21 (70%)
      sustained injury to cervical cord, 3 (10%) had thoracic and 6 (20%) had lumbar
      spine fractures. In all, 23 patients (77%) were treated by orthosis and 7 (23%)
      underwent surgical intervention. Twelve (40%) patients showed an improvement in
      American Spinal Injury Association impairment scale. The median hospital stay was
      136 days. Thus, 11 patients (37%), all with incomplete injuries, were discharged
      home, 10 (33%) were transferred to nursing homes/community hospitals and 9
      patients (30%) were discharged back to the referring hospital, while they were
      awaiting adjustments at home. Patients who were discharged home had significantly
      higher Functional Independence Measure scores, both at the onset of
      rehabilitation and at discharge, than those who were discharged to a nursing home
      or other hospitals (P<0.01 and <0.001, respectively). DISCUSSION AND CONCLUSION:
      Although the elderly patients may benefit from the services of a dedicated spinal
      injuries centre, they should be carefully selected. The patient, relatives as
      well as the referring doctors should be alerted to the likely long-term outcomes
      early in the course of the injury. Elderly patients with complete lesions of the
      spinal cord will almost certainly remain institutionalized. Early endeavour
      should be made to find alternate rehabilitation settings with a lower-intensity
      treatment.

PMID- 20697422
TI  - Quality of life in adults with spinal cord injury living in the community.
AB  - STUDY DESIGN: The study design used is cross-sectional descriptive survey.
      OBJECTIVES: The aim of this study is to describe the subjective and objective
      quality of life (QoL) of adults with chronic non-traumatic spinal cord injury (NT
      SCI) and to compare the objective and subjective QoL of adults with chronic NT
      SCI with adults who have a chronic traumatic spinal cord injury (T-SCI) and the
      general population. SETTING: Living in the general community (non-residential
      care), Australia. PARTICIPANTS: The study included 443 adults with SCI (T-SCI,
      n=381) (NT-SCI, n=62), all SCI >=6 months duration. INTERVENTION: Not applicable.
      MAIN OUTCOME MEASURES: Objective and subjective QoL domains--Comprehensive QoL
      Scale for Adults, version 5 (COMQoL-A5); acceptance subscale--the Spinal Cord
      Lesion Coping Strategies Questionnaire, version 1 Australia (SCL CSQ v1.0
      Australia). RESULTS: Despite demographic differences, only the objective QoL
      domain material (higher in NT-SCI) and the subjective QoL domain health (lower in
      NT-SCI) were significantly different between the SCI subgroups. In contrast, five
      of the seven objective domains and four of the seven subjective domains were
      significantly lower in the SCI sample as a whole, compared with the general
      population. Post hoc analyses suggested that aetiology of the SCI was not
      responsible for QoL differences within the cohort with SCI. CONCLUSION: On the
      whole, aetiology makes little difference to QoL outcomes after SCI. The QoL of
      adults with chronic T-SCI and NT-SCI fall significantly below that of the general
      population in most domains.

PMID- 20697423
TI  - Evolution and development of shape: integrating quantitative approaches.
AB  - Morphological traits have long been a focus of evolutionary developmental biology
      ('evo-devo'), but new methods for quantifying shape variation are opening
      unprecedented possibilities for investigating the developmental basis of
      evolutionary change. Morphometric analyses are revealing that development
      mediates complex interactions between genetic and environmental factors affecting
      shape. Evolution results from changes in those interactions, as natural selection
      favours shapes that more effectively perform some fitness-related functions.
      Quantitative studies of shape can characterize developmental and genetic effects
      and discover their relative importance. They integrate evo-devo and related
      disciplines into a coherent understanding of evolutionary processes from
      populations to large-scale evolutionary radiations.

PMID- 20697425
TI  - Distinct roles in NKT cell maturation and function for the different
      transcription factors in the classical NF-kappaB pathway.
AB  - The nuclear factor (NF)-kappaB signalling pathway is known to be critical for
      natural killer T (NKT) cell differentiation; however, the role of individual NF
      kappaB transcription factors and the precise developmental stages that they
      control remain unclear. We have investigated the influence of the classical NF
      kappaB transcription factors NF-kappaB1, c-Rel and RelA on NKT cell development
      and function, using gene-deleted mice. Individually, none of these factors were
      essential for the requirement of NF-kappaB signalling in early NKT cell
      development before NK1.1 expression, in contrast to earlier reports in which the
      classical NF-kappaB pathway was globally disrupted. Instead, we found that each
      factor played a non-redundant role in later stages of NKT cell maturation and
      function. Although NF-kappaB1 deficiency resulted in a moderate reduction in
      mature NK1.1+ NKT cells, this was found to be more subtle than previously
      reported. RelA deficiency had a more profound effect on the NK1.1+ stage of NKT
      cell development, whereas c-Rel-deficient mice had normal NKT cell numbers. All
      three factors (NF-kappaB1, RelA and c-Rel) were necessary for normal NKT cell
      cytokine production. Notably, IL-17, which is produced by a specific subset of
      NKT cells (NKT-17 cells), defined as NK1.1(-)CD4(-), was not impaired by a lack
      of these individual NF-kappaB transcription factors, nor was this subset
      depleted, suggesting that NKT-17 cells are regulated independently of the NF
      kappaB pathway. Thus, individual NF-kappaB family members have a largely
      redundant role in early NKT cell development, but each of them has an important
      and distinct role in NKT cell maturation and/or function.

PMID- 20697424
TI  - Secondary stroke prevention.
AB  - Secondary stroke prevention can reduce the risk of recurrent stroke by
      approximately 90%. To achieve such a reduction, early implementation of
      preventative measures and administration of therapy appropriate to the underlying
      cause of the presenting transient ischemic attack or stroke are crucial. Smoking
      cessation and a Cretan Mediterranean diet are each more effective than any single
      medication in reducing the risk of recurrent stroke. Control of resistant
      hypertension can markedly reduce the risk of intracerebral hemorrhage and lacunar
      infarction but might require therapy that is specific to the underlying cause.
      New antiplatelet agents have been developed or are in development that might
      avoid the issues of resistance and drug interactions that prevail with
      established agents of this type. Furthermore, new anticoagulants in development
      offer promise of replacing warfarin, and devices to occlude the atrial appendage
      are on the horizon for patients with atrial fibrillation. Carotid endarterectomy
      is appropriate for severe symptomatic carotid stenosis, while stenting might be
      appropriate for symptomatic stenosis where the surgical risk is high. Most
      patients with asymptomatic stenosis, however, should be treated with medical
      therapy, unless indicators of high stroke risk are present. In this narrative
      Review, I discuss recent advances in secondary stroke prevention.

PMID- 20697427
TI  - Sequential changes in gene expression profiles in breast cancers during treatment
      with the aromatase inhibitor, letrozole.
AB  - The study aim was to identify early (within 14 days) and late changes (by 3
      months) in breast cancer gene expression profiles associated with neoadjuvant
      therapy with letrozole. RNA from sequential tumour biopsies in 54 patients was
      analyzed on microarrays; changes were determined by frequency, magnitude and
      significance analyses. Substantially more genes were changed at 3 months (1503)
      than at 14 days (237). Early changed genes were associated with cell cycle
      (downregulation), blood vessel development and extracellular matrix
      (upregulation); late changes included 'cellular metabolic process', 'generation
      of precursor metabolites and energy' (decreased) and 'cell adhesion' 'biological
      adhesion' (increased). A striking difference between the early and late changes
      was the general location of downregulated genes-nuclear structures at 14 days and
      mitochondria after 3 months. These changes in gene expression profiles provide a
      new and important database by which to understand molecular mechanisms of
      letrozole in breast cancers.

PMID- 20697426
TI  - CD40 engagement on dendritic cells induces cyclooxygenase-2 and EP2 receptor via
      p38 and ERK MAPKs.
AB  - We have previously reported that cyclooxygenase (COX)-2-derived prostaglandin
      (PG)E2 critically regulates dendritic cell (DC) inflammatory phenotype and
      function through EP2/EP4 receptor subtypes. As genes activated by CD40 engagement
      are directly relevant to inflammation, we examined the effects of CD40 activation
      on inflammatory PGs in murine bone marrow-derived DC (mBM-DC). We showed for the
      first time that activation of mBM-DC with agonist anti-CD40 monoclonal antibody
      (anti-CD40 mAb) dose dependently induces the synthesis of significant amounts of
      PGE2 via inducible expression of COX-2 enzyme, as NS-398, a COX-2-selective
      inhibitor reduces this upregulation. In contrast to lipopolysaccharide, which
      upregulates mBM-DC surface levels of EP2 and EP4 receptors, CD40 crosslinking on
      mBM-DC increases EP2, but not EP4, receptor expression. Flow cytometry analysis
      and radioligand-binding assay showed that EP2 was the major EP receptor subtype,
      which binds to PGE2 at the surface of anti-CD40-activated mBM-DC. Upregulation of
      COX-2 and EP2 levels by CD40 engagement was accompanied by dose-dependent
      phosphorylation of p38 and ERK1/2 mitogen-activated protein kinase (MAPK) and was
      abrogated by inhibitors of both pathways. Collectively, we demonstrated that CD40
      engagement on mBM-DC upregulates COX-2 and EP2 receptor expression through
      activation of p38 and ERK1/2 MAPK signaling. Triggering the PGE2/EP2 pathway by
      anti-CD40 mAb resulted on the induction of Th2 immune response. Thus, CD40
      induced production of PGE2 by mBM-DC could represent a negative feedback
      mechanism involving EP2 receptor and limiting the propagation of Th1 responses.
      Blocking CD40 pathway may represent a novel therapeutic pathway of inhibiting COX
      2-derived prostanoids in chronically inflamed tissues (that is, arthritis).

PMID- 20697428
TI  - Genetic variation in adiponectin (ADIPOQ) and the type 1 receptor (ADIPOR1),
      obesity and prostate cancer in African Americans.
AB  - Adiponectin is a protein derived from adipose tissue suspected to have an
      important role in prostate carcinogenesis. Variants in the adiponectin gene
      (ADIPOQ) and its type 1 receptor (ADIPOR1) have been recently linked to risk of
      both breast and colorectal cancer. Therefore, we set out to examine the
      relationship between polymorphisms in these genes, obesity and prostate cancer in
      study of African-American men. Ten single-nucleotide polymorphisms (SNPs) in
      ADIPOQ and ADIPOR1 were genotyped in DNA samples from 131 African-American
      prostate cancer cases and 344 controls participating in the Flint Men's Health
      Study. Logistic regression was then used to estimate their association with
      prostate cancer and obesity. While no significant associations were detected
      between any of the tested SNPs and prostate cancer, the rs1501299 SNP in ADIPOQ
      was significantly associated with body mass (P=0.03). Genetic variation in ADIPOQ
      and ADIPOR1 did not predict risk of prostate cancer in this study of African
      American men. However, the rs1501299 SNP in ADIPOQ was associated with obesity.
      Further investigation is warranted to determine if racial differences exist in
      the influence of the adiponectin pathway on prostate cancer risk.

PMID- 20697429
TI  - An imprinted signature helps isolate ESC-equivalent iPSCs.

PMID- 20697430
TI  - VEGFR-3 ligand-binding and kinase activity are required for lymphangiogenesis but
      not for angiogenesis.
AB  - Although VEGFR-3 deficiency disrupts blood vascular development during early
      embryogenesis, the underlying mechanism was not clear. To characterize its
      function in angiogenesis and lymphangiogenesis, we employed two genetically
      modified mouse models in this study, targeting the coding region for the ligand
      binding domain (Vegfr3(DeltaLBD)) or the tyrosine kinase domain with an
      inactivation point mutation (Vegfr3(TKmut)). We show that lymphatic growth was
      disrupted in Vegfr3(DeltaLBD/DeltaLBD) and Vegfr3(TKmut/TKmut) mice, but blood
      vessels developed normally in both embryo and yolk sac. Interestingly, in
      Vegfr3(DeltaLBD/DeltaLBD) but not Vegfr3(TKmut/TKmut) mice, lymph sac was present
      but there was lack of lymphangiogenic sprouting. We further demonstrate that both
      the wild-type and mutant forms of VEGFR-3 could form heterodimers with VEGFR-2,
      and decreased the level of phospho-VEGFR-2 and the downstream phospho-Erk1/2 in
      endothelial cells when they were treated with VEGF-A. These findings indicate
      that signaling mediated via VEGFR-3 activation by its cognate ligands (VEGF-C/-D)
      is not required for angiogenesis, and that VEGFR-3 may play a role in this
      process by modulating VEGFR-2-mediated signals.

PMID- 20697433
TI  - Coherent optical ultrasound detection with rare-earth ion dopants.
AB  - We describe theoretical and experimental demonstration for optical detection of
      ultrasound using a spectral hole engraved in cryogenically cooled rare-earth ion
      doped solids. Our method utilizes the dispersion effects due to the spectral hole
      to perform phase-to-amplitude modulation conversion. Like previous approaches
      using spectral holes, it has the advantage of detection with large etendue. The
      method also has the benefit that high sensitivity can be obtained with moderate
      absorption contrast for the spectral holes.

PMID- 20697432
TI  - Complicated urethroplasty: a guide for surgeons.
AB  - Although straightforward male urethral stricture disease is commonly encountered
      in the scope of general urologic practice, complex urethral strictures are less
      common and require a more systematic approach. Complex urethral stricture surgery
      for long and panurethral strictures, after failed hypospadias repair, and for
      recurrent posterior urethral distraction defects requires a dynamic treatment
      paradigm. A multistaged urethral reconstruction is often necessary owing to
      hostile urethral tissue, especially after multiple previous procedures. A
      perineal urethrostomy sometimes offers improved quality of life for patients with
      complex urethral stricture disease, particularly if they have undergone previous
      failed repairs. Recurrent posterior urethral distraction defects are best treated
      with excision of the scarred urethral segment and re-anastomosis. Urethral
      stricture disease after treatment for prostate cancer requires multiple treatment
      approaches given the often poor tissue quality and likelihood of stricture
      recurrence.

PMID- 20697431
TI  - EphA3 functions are regulated by collaborating phosphotyrosine residues.
AB  - Ephrin ligands interact with Eph receptors to regulate a wide variety of
      biological and pathological processes. Recent studies have identified several
      downstream pathways that mediate the functions of these receptors. Activation of
      the receptors by ephrin binding results in the phosphorylation of the receptor
      tyrosine residues. These phosphorylated residues serve as docking sites for many
      of the downstream signaling pathways. However, the relative contributions of
      different phosphotyrosine residues remain undefined. In the present study, we
      mutated each individual tyrosine residues in the cytoplasmic domain of EphA3
      receptor and studied the effects using cell migration, process retraction, and
      growth cone collapse assays. Stimulation of the EphA3 receptor with ephrin-A5
      inhibits 293A cell migration, reduces NG108-15 cell neurite outgrowth, and
      induces growth cone collapse in hippocampal neurons. Mutation of either Y602 or
      Y779 alone partially decreases EphA3-induced responses. Full abrogation can only
      be achieved with mutations of both Y602 and Y779. These observations suggest a
      collaborative model of different downstream pathways.

PMID- 20697434
TI  - Shot-noise-limited control-loop noise in an interferometer with multiple degrees
      of freedom.
AB  - Precise measurements, such as those made with interferometric gravitational-wave
      detectors, require the measurement device to be properly controlled so that the
      sensitivity can be as high as possible. Mirrors in the interferometer are to be
      located at specific operation points to isolate laser noise and to accumulate the
      signal in resonant cavities. On the other hand, rigid control of an auxiliary
      degree of freedom may result in imposing sensing noise of the control on the
      target object as excess force noise. Evaluation of this so-called loop noise is
      important in order to design a decent control scheme of the measurement device.
      In this paper, we show the method to calculate the level of loop noise, which has
      been recently implemented in simulation tools that are broadly used for designing
      gravitational-wave detectors.

PMID- 20697436
TI  - Form birefringence in intrinsic birefringent media possessing a subwavelength
      structure.
AB  - We theoretically investigate optical birefringence originating from subwavelength
      structures in intrinsic birefringent media. Assuming alternating layers of
      isotropic and anisotropic materials, the propagation of optical waves is
      simulated on the basis of the finite difference time domain method. Optical
      polarization changes throughout the structure reveal the birefringence of the
      layered structure as a whole. In addition, the birefringence is also analyzed on
      the basis of effective medium theory. The results indicate that the optical
      birefringence of the structure as a whole can be modified by the magnitude and
      direction of the intrinsic birefringence of the anisotropic layers. This
      theoretical prediction will be useful for micro- and nanofabrication in optical
      devices.

PMID- 20697437
TI  - Detection of explosives based on surface-enhanced Raman spectroscopy.
AB  - In this study we present a device based on surface-enhanced Raman scattering
      (SERS) for the detection of airborne explosives. The explosives are resublimated
      on a cooled nanostructured gold substrate. The explosives trinitrotoluene (TNT)
      and triacetone triperoxide (TATP) are used. The SERS spectrum of the explosives
      is analyzed. Thus, TNT is deposited from an acetonitrile solution on the gold
      substrate. In the case of TATP, first the bulk TATP Raman spectrum was recorded
      and compared with the SERS spectrum, generated by deposition out of the gas
      phase. The frequencies of the SERS spectrum are hardly shifted compared to the
      spectrum of bulk TATP. The influence of the nanostructured gold substrate
      temperature on the signals of TATP was studied. A decrease in temperature up to
      200 K increased the intensities of the TATP bands in the SERS spectrum; below 200
      K, the TATP fingerprint disappeared.

PMID- 20697435
TI  - Multi-projection fluorescence optical tomography using a handheld-probe-based
      optical imager: phantom studies.
AB  - A handheld-probe-based optical imager has recently been developed toward three
      dimensional tomography. In this study, the improvement of target depth recovery
      was demonstrated using a multi-projection technique on large slab phantoms using
      0.45 cc fluorescing target(s) (with 1:0 contrast ratio) of 1.5 to 2.5 cm deep.
      Tomographic results using single- and multi- (here dual) projection measurements
      (with and without a priori information of target location) were compared. In all
      experimental cases, the use of multi-projection measurements along with a priori
      information recovered target depth and location closer to their true values,
      demonstrating its applicability for clinical translation.

PMID- 20697438
TI  - Challenge of false alarms in nitroaromatic explosive detection--a detection
      device based on surface-enhanced Raman spectroscopy.
AB  - A challenge in the detection of explosives is the differentiation between
      explosives and contaminants. Synthetic musk-containing perfumes can cause false
      alarms, as these perfumes are nitroaromatic compounds, which can be mistaken for
      trinitro toluene (TNT) by some detectors. We present a detection principle based
      on surface-enhanced Raman scattering (SERS). A stream of the airborne compounds
      is focused and resublimated on a cooled nanostructured gold surface. We recorded
      high-resolution SERS spectra of TNT, musk xylene, and musk ketone. The
      nitroaromatic compounds can be identified unambiguously by their SERS spectra.
      Even the dominant bands containing nitro-group scissoring and symmetric
      stretching modes are significantly shifted by the difference in molecular
      structure.

PMID- 20697439
TI  - Spatial resolution of a hard x-ray CCD detector.
AB  - The spatial resolution of an x-ray CCD detector was determined from the widths of
      the tungsten x-ray lines in the spectrum formed by a crystal spectrometer in the
      58 to 70 keV energy range. The detector had 20 microm pixel, 1700 by 1200 pixel
      format, and a CsI x-ray conversion scintillator. The spectral lines from a
      megavolt x-ray generator were focused on the spectrometer's Rowland circle by a
      curved transmission crystal. The line shapes were Lorentzian with an average
      width after removal of the natural and instrumental line widths of 95 microm
      (4.75 pixels). A high spatial frequency background, primarily resulting from
      scattered gamma rays, was removed from the spectral image by Fourier analysis.
      The spectral lines, having low spatial frequency in the direction perpendicular
      to the dispersion, were enhanced by partially removing the Lorentzian line shape
      and by fitting Lorentzian curves to broad unresolved spectral features. This
      demonstrates the ability to improve the spectral resolution of hard x-ray spectra
      that are recorded by a CCD detector with well-characterized intrinsic spatial
      resolution.

PMID- 20697440
TI  - Design of achromatic and apochromatic plastic micro-objectives.
AB  - The possibility and the efficiency of using a single diffractive lens to
      achromatize and apochromatize micro-objectives with plastic lenses are shown. In
      addition, recommendations are given on assembling the starting configurations of
      the objectives and calculating the design parameters required for subsequent
      optimization. It is also shown that achievable optical performance of achromatic
      and apochromatic micro-objectives with plastic lenses satisfy the qualifying
      standards for cell-phone objectives and closed-circuit television (CCTV) cameras.

PMID- 20697441
TI  - Very efficient speckle contrast reduction realized by moving diffuser device.
AB  - Speckle noise reduction is best tested on a precise speckle contrast measurement
      bench, which should be able to measure 100% contrast in fully developed speckle
      as well as the smallest contrast (for example, less than 10%) after its
      reduction. On such a test bench, we have measured very efficient speckle contrast
      reduction by temporal averaging using a moving diffuser on a tuning fork, which
      vibrates at 100 Hz over 60 microm in amplitude, a distance that is three times
      the surface roughness correlation length of the diffuser.

PMID- 20697442
TI  - Improved measurement linearity and precision for AMCW time-of-flight range
      imaging cameras.
AB  - Time-of-flight range imaging systems utilizing the amplitude modulated continuous
      wave (AMCW) technique often suffer from measurement nonlinearity due to the
      presence of aliased harmonics within the amplitude modulation signals. Typically
      a calibration is performed to correct these errors. We demonstrate an alternative
      phase encoding approach that attenuates the harmonics during the sampling
      process, thereby improving measurement linearity in the raw measurements. This
      mitigates the need to measure the system's response or calibrate for
      environmental changes. In conjunction with improved linearity, we demonstrate
      that measurement precision can also be increased by reducing the duty cycle of
      the amplitude modulated illumination source (while maintaining overall
      illumination power).

PMID- 20697443
TI  - Software configurable optical test system: a computerized reverse Hartmann test.
AB  - A software configurable optical test system (SCOTS) based on the geometry of the
      fringe reflection or phase measuring deflectometry method was developed for
      rapidly, robustly, and accurately measuring large, highly aspherical shapes such
      as solar collectors and primary mirrors for astronomical telescopes. In addition
      to using phase shifting methods for data collection and reduction, we explore the
      test from the point view of performing traditional optical testing methods, such
      as Hartmann or Hartmann-Shack tests, in a reverse way. Using this concept, the
      slope data calculation and unwrapping in the test can also be done with
      centroiding and line-scanning methods. These concepts expand the test to work in
      more general situations where fringe illumination is not practical. Experimental
      results show that the test can be implemented without complex calibration for
      many applications by taking the geometric advantage of working near the center
      curvature of the test part. The results also show that the test has a large
      dynamic range, can achieve measurement accuracy comparable with interferometric
      methods, and can provide a good complement to interferometric tests in certain
      circumstances. A variation of this method is also useful for measuring refractive
      optics and optical systems. As such, SCOTS provides optical manufacturers with a
      new tool for performing quantitative full field system evaluation.

PMID- 20697444
TI  - Time-domain optical reflectometry measurements using a frequency comb
      interferometer.
AB  - We characterize the temporal response of fiber-optic components using a fiber
      based frequency comb interferometer; measurements are compared and validated
      against a commercial instrument. The main advantage of the instrument lies in the
      absence of moving parts or a tunable laser, leading to very fast scanning. A
      measurement of a mechanical distortion, cycled at 130 Hz, on a fiber Bragg
      grating (FBG) is presented. A complete profile of the mechanical distortion is
      taken every 2.5 ms (400 Hz scanning speed) and each "snapshot" is taken in 200
      micros. This scanning speed was arbitrarily chosen, and the instrument could be
      set to scan much faster, up to hundreds of kilohertz. With high-reflectivity
      FBGs, the same instrument could scan simultaneously the profile of 140 wavelength
      multiplexed FBGs at 2 kHz.

PMID- 20697445
TI  - Simultaneous displacement and angular drift measurement based on defocus grating.
AB  - We propose and demonstrate a displacement and angular drift simultaneous
      measurement technique based on a defocus grating. The displacement and angular
      drift of the incident beam can be detected by monitoring the movements of +/-1
      diffraction order spots of the defocus grating. The relationship between drift of
      the incident beam and movements of +/-1 diffraction order spots is studied in
      detail. Compared with other methods, this technique eliminates the requirement of
      two or more detecting systems for measuring displacement and angular drift
      simultaneously. The proof-of-principle experiment shows that the root-mean-square
      errors of displacement and angular drift measurements are less than 0.5 microm
      and 0.84 microrad, respectively.

PMID- 20697446
TI  - Optical heterodyne accelerometry: passively stabilized, fully balanced velocity
      interferometer system for any reflector.
AB  - We formalize the physics of an optical heterodyne accelerometer that allows
      measurement of low and high velocities from material surfaces under high strain.
      The proposed apparatus incorporates currently common optical velocimetry
      techniques used in shock physics, with interferometric techniques developed to
      self-stabilize and passively balance interferometers in quantum cryptography. The
      result is a robust telecom-fiber-based velocimetry system insensitive to modal
      and frequency dispersion that should work well in the presence of decoherent
      scattering processes, such as from ejecta clouds and shocked surfaces.

PMID- 20697447
TI  - Removal characteristics of plasma chemical vaporization machining with a pipe
      electrode for optical fabrication.
AB  - Plasma chemical vaporization machining (CVM) is a high-precision chemical shaping
      method using rf plasma generated in the proximity of an electrode in an
      atmospheric environment. The purpose of the present study is to clarify the
      removal characteristics of plasma CVM using a pipe electrode. Polished fused
      silica plates were processed by plasma CVM, polishing, and precision grinding
      under various conditions. The removal rate of plasma CVM was about 4 to 1100
      times faster than that of polishing, and the maximum removal rate was almost
      equal to that of precision grinding. The roughness of the resultant surfaces was
      almost the same as that of the polished surfaces.

PMID- 20697448
TI  - Backscattering linear depolarization ratio measurements of mineral, sea-salt, and
      ammonium sulfate particles simulated in a laboratory chamber.
AB  - The backscattering linear depolarization ratios of major types of tropospheric
      aerosol particles (Asian and Saharan mineral dust, sea salt, and ammonium
      sulfate) were measured using a laboratory chamber for interpreting the
      polarization lidar measurement of tropospheric aerosols. The values obtained from
      Asian and Saharan mineral particles were 0.39 +/- 0.04 to 0.05 (mean +/- standard
      deviation) for a high number of concentrations in the supermicrometer range and
      0.17 +/- 0.03 to 0.14 +/- 0.03 in the submicrometer range. The values were 0.08
      +/- 0.01 for sea-salt crystals, 0.04 +/- 0.003 for ammonium sulfate crystals, and
      0.01 +/- < or = 0.001 for both liquid droplets in the submicrometer range. These
      values can serve as a reference for estimating aerosol type using lidar
      measurement.

PMID- 20697449
TI  - Investigation on the properties of a laminar grating as a soft x-ray beam
      splitter.
AB  - Laminar-type gratings as soft x-ray beam splitters for interferometry are
      presented. Gold-coated grating beam splitters with 1000 lines/mm are designed for
      grazing incidence operation at 13.9 nm. They are routinely fabricated using
      electron beam lithography and ion etching techniques. The laminar grating is
      measured to have almost equal absolute efficiencies of about 20% in the zeroth
      and -1st orders, which enables a fringe visibility up to 0.99 in the
      interferometer. The discrepancy of the grating profiles between the optimized
      theoretical and the experimental results is analyzed according to the comparison
      of the optimized simulation results and the measurement realization of the
      grating efficiencies. By a precise control of the grating profile, the grating
      efficiency in the -1st order and the fringe visibility could be improved to 25%
      and 1, respectively.

PMID- 20697450
TI  - Modeling and interpretation of extinction spectra of oriented nonspherical
      composite particles: application to biological cells.
AB  - The majority of cells and microorganisms have a nonspherical shape and complex
      structure that challenge the interpretation of their spectral features. To
      address this issue, two approximations to the core-shell Mie theory were
      proposed. These included the approximation of light extinction by an ellipsoid
      with representation of the extinction by an equivalent sphere and representation
      of the extinction by a population of ellipsoidal particles with those of two
      weighted particle orientations. These hypotheses were first tested through
      numerical interpretation of the theoretical extinction spectra of prolate
      nucleated ellipsoids mimicking biological cells generated with anomalous
      diffraction approximation used as a reference method. Theoretical cases of fixed
      and random particle orientations demonstrated excellent capabilities of the
      proposed approach to retrieve the size, shape, and composition parameters of the
      model particles. Second, the UV-visible spectra of Leishmania species,
      promastigotes, elongated cells with prominent nuclei, were interpreted. The
      retrieved estimates of the protozoa size, shape, nucleus size, and nucleotide
      composition were in agreement with the corresponding microscopy estimates and
      literature values. Both theoretical tests and experimental results illustrated
      that the proposed approach can be successfully applied to estimate the structural
      and compositional parameters of cells from spectroscopic measurements.

PMID- 20697451
TI  - Solar concentrator constructed with a circular prism array.
AB  - We present a novel idea to construct a solar concentrator with a circular prism
      array. FRED ray tracing software is used to evaluate our proposed structure in
      which the incident light rays are deflected by total internal reflection and the
      optical energy is concentrated and collected at the center. The light rays to be
      collected travel within the disk once they enter the module, saving the space
      that is reserved for ray propagation in other concentrators. Simulations for both
      single-wavelength and broadband light are performed. Our device can be used alone
      or serve as a secondary concentrator when combined with another solar-energy
      focusing module. For the proposed concentrator, an optical efficiency of 90%
      (single wavelength, 0.87 microm) is achieved under normal incidence and with
      antireflection coating, and a high geometric concentration ratio of 93 is
      reached. When combined with a Fresnel lens, which is used as a primary
      concentrator, the overall efficiency and concentration ratio can reach 92%
      (single wavelength, 0.87 microm) and 837, respectively.

PMID- 20697452
TI  - Three-dimensional, arbitrary orientation of focal polarization.
AB  - We demonstrate a simple setup for generating a three-dimensional arbitrary
      orientation of the polarization vector in a laser focus. The key component is the
      superposition of a linearly and a radially polarized laser beam, which both can
      be controlled individually in intensity and relative phase. We exemplify the
      usefulness of this setup by determining the spatial orientation of a single
      silver nanorod in three-dimensional space by recording the angle-variable
      backscattered light intensity.

PMID- 20697453
TI  - Blowing in the Wind: Unanchored Patient Information Work during Cancer Care.
AB  - Patients do considerable information work. Technologies that help patients manage
      health information so they can play active roles in their health-care, such as
      personal health records, provide patients with effective support for focused and
      sustained personal health tasks. Yet, little attention has been paid to patients'
      needs for information management support while on the go and away from their
      personal health information collections. Through a qualitative field study, we
      investigated the information work that breast cancer patients do in such
      'unanchored settings'. We report on the types of unanchored information work that
      patients do over the course of cancer treatment, reasons this work is
      challenging, and strategies used by patients to overcome those challenges. Our
      description of unanchored patient information work expands our understanding of
      patients' information practices and points to valuable design directions for
      supporting critical but unmet needs.

PMID- 20697454
TI  - CASE REPORT Febrile Ulceronecrotic Mucha-Habermann Disease.
AB  - OBJECTIVE: Case report and review of the current literature about febrile
      ulceronecrotic Mucha-Habermann disease (FUMHD). METHODS: Review of our patient's
      medical records and of the current literature. RESULTS: The FUMHD is a rare and
      potentially lethal type of pityriasis lichenoides et varioliformis acuta. It is
      characterized by the sudden onset of ulceronecrotic skin lesions associated with
      high fever and systemic symptoms. Because of a high case-fatality rate it
      requires quick and decisive action. Only 40 cases of this severe form of the
      disease have been reported in the literature to date. We present the case of a 30
      year-old male patient with severe FUMHD who was successfully treated in our burn
      intensive care unit after failed treatment at a dermatological hospital. The
      patient was treated with topical antiseptics, moisturizers, and artificial skin
      substitutes, as well as systemic immunosuppressive therapy (glucocorticoids) with
      which we were able to control the disease activity so that healing of the
      patient's skin lesions could be achieved. CONCLUSION: Patients with FUMHD should
      be treated in a specialized center for severely burned patients. Only such
      centers can provide the structural and logistical capacities necessary for the
      treatment of such extensive superficial wounds.

PMID- 20697455
TI  - CASE REPORT Type II Metacarpal Hands: Reconstruction Planning Revisited.
AB  - OBJECTIVE: Successful reconstruction of the metacarpal hand requires thorough
      evaluation and careful surgical planning. Effective transplantation involves 3
      main considerations: residual hand function, functional needs and desires of the
      patient, and optimal surgical management to maximize outcome and minimize patient
      morbidity. METHODS: The following is a clinical example of the metacarpal hand in
      which the patient underwent initial reconstruction at an outside hospital and was
      referred to our institution. This demonstrates how the initial planning and
      surgical management could have been further optimized to minimize functional
      deficits and donor-site morbidities as well as reduce the number of subsequent
      revisional surgeries and rehabilitation time. RESULTS: Several important points
      in metacarpal hand reconstruction are described given specific level of
      amputation and residual function after the injury-the timing and sequence of
      operative strategy depending on the type of injury, the selection of donor-site
      digit transfers, and the overall treatment strategies for thumb and finger
      reconstruction. CONCLUSION: It is important to follow proper treatment algorithms
      in order to determine appropriate timing and sequence of toe-to-digit transfers,
      multi-stage versus 1-stage, as well as define the reconstructive goal to achieve
      a tripod pinch for a unilateral or a dominant hand injury or a pulp-to-pulp
      opposition for nondominant injury in bilateral cases. If adequate planning is
      performed, unnecessary and additional surgical procedures as well as increased
      patient suffering and prolonged rehabilitation time can be prevented or
      optimized.

PMID- 20697456
TI  - CASE REPORT Playing Football Burns More Than Just Calories.
AB  - OBJECTIVE: To highlight the case of a sports-related alkali burn due to a common
      household chemical and emphasize the importance of a detailed medical history in
      chemical burns patients. METHODS: A single-patient case study is presented along
      with references from existing literature. RESULTS: Alkaline burn injuries
      associated with sports have previously been described in the literature; however,
      this case demonstrates an unusual presentation of a chemical burn with a readily
      available household substance. CONCLUSION: Chemical burns can present in atypical
      ways. Detailed history and thorough clinical examination is essential in
      determining the correct diagnosis and therefore implementing the most appropriate
      management plan.

PMID- 20697458
TI  - Race/Ethnic Differences in Effects of Family Instability on Adolescents' Risk
      Behavior.
AB  - We used data from the National Longitudinal Study of Adolescent Health (N =
      7,686) to determine whether racial and ethnic differences in socioeconomic stress
      and social protection explained group differences in the association between
      family structure instability and three risk behaviors for White, Black, and
      Mexican American adolescents: delinquent behavior, age at first nonmarital sex,
      and age at first nonmarital birth. The positive association between mothers'
      union transitions and each outcome for White adolescents was attenuated by social
      protection. The association of instability with age at first sex and first
      nonmarital birth was weaker for Black adolescents, but not for Mexican American
      adolescents. The weaker association was explained by Black adolescents' more
      frequent exposure to socioeconomic stress in the context of union instability.

PMID- 20697457
TI  - A palladium-catalysed enolate alkylation cascade for the formation of adjacent
      quaternary and tertiary stereocentres.
AB  - The catalytic enantioselective synthesis of densely functionalised organic
      molecules containing all-carbon quaternary stereocentres is a challenge to modern
      chemical methodology research. The catalytically controlled asymmetric alpha
      alkylation of ketones represents another difficult task and has been of major
      interest to our and other research groups in the past. We now report a palladium
      catalyzed enantioselective process that addresses both problems at once and
      allows the installation of vicinal all-carbon quaternary and tertiary
      stereocentres at the alpha-carbon of a ketone in a single step. This multiple
      bond forming process is carried out on readily available beta-ketoester starting
      materials and proceeds via conjugate addition of an in situ-generated palladium
      enolate to activated Michael acceptors. In other words, the CO(2)-moiety of the
      substrate is displaced by a C-C fragment in an asymmetric cut-and-paste reaction.
      The products are obtained in high yield, diastereomeric ratio, and enantiomeric
      excess.

PMID- 20697459
TI  - Multicomponent Breath Analysis With Infrared Absorption Using Room-Temperature
      Quantum Cascade Lasers.
AB  - Breath analysis is a powerful noninvasive technique for the diagnosis and
      monitoring of respiratory diseases, including asthma and chronic obstructive
      pulmonary disease (COPD). Nitric oxide (NO) and carbon monoxide (CO) are markers
      of airway inflammation and can indicate the extent of respiratory diseases. We
      have developed a compact fast response laser system for analysis of multiple
      gases by infrared absorption. The instrument uses room temperature quantum
      cascade lasers to simultaneously measure NO, CO, carbon dioxide (CO(2)) and
      nitrous oxide (N(2)O) in exhaled breath. Four breath flow rates are employed to
      explore their exchange dynamics in the lungs and airways. We obtain 1-s detection
      precisions of 0.5-0.8 parts-per-billion (ppb) for NO, CO, and N(2)O with an
      instrument response time of less than 1 s. The breath analysis system has been
      demonstrated in a preliminary study of volunteers. It is currently deployed in a
      trial clinical study.

PMID- 20697460
TI  - Total synthesis of neopeltolide and analogs.
AB  - Neopeltolide, a potent cytotoxin from a Carribean sponge, was synthesized through
      a brief sequence that highlights the use of ethers as oxocarbenium ion
      precursors. Other key steps include an acid-mediated etherification and sequence
      that features a Sonogashira reaction, an intramolecular alkyne hydrosilylation
      reaction, and a Tamao oxidation. The alkene that is required for the oxidative
      cyclization can be hydrogenated to provide access to the natural product or an
      epimer, or can be epoxidized or dihydroxylated to form polar analogs.

PMID- 20697461
TI  - Optoelectrofluidic field separation based on light-intensity gradients.
AB  - Optoelectrofluidic field separation (OEFS) of particles under light -intensity
      gradient (LIG) is reported, where the LIG illumination on the photoconductive
      layer converts the short-ranged dielectrophoresis (DEP) force to the long-ranged
      one. The long-ranged DEP force can compete with the hydrodynamic force by
      alternating current electro-osmosis (ACEO) over the entire illumination area for
      realizing effective field separation of particles. In the OEFS system, the
      codirectional illumination and observation induce the levitation effect,
      compensating the attenuation of the DEP force under LIG illumination by slightly
      floating particles from the surface. Results of the field separation and
      concentration of diverse particle pairs (0.82-16 mum) are well demonstrated, and
      conditions determining the critical radius and effective particle manipulation
      are discussed. The OEFS with codirectional LIG strategy could be a promising
      particle manipulation method in many applications where a rapid manipulation of
      biological cells and particles over the entire working area are of interest.

PMID- 20697462
TI  - Fast three dimensional ac electro-osmotic pumps with nonphotolithographic
      electrode patterning.
AB  - Three dimensional (3D) stepped electrodes dramatically improve the flow rate and
      frequency range of ac electro-osmotic pumps, compared to planar electrodes.
      However, the fabrication of 3D stepped electrodes for ac electro-osmosis (ACEO)
      pumps usually involves several processing steps. This paper demonstrates results
      from ACEO pumps produced by a faster and less expensive method to fabricate the
      3D electrodes-extending the previous work to disposable devices. The method is
      based on shadowed evaporation of metal on an insulating substrate that can be
      injection molded. Flow velocities through the 3D ACEO pump are similar to those
      seen in the previous work.

PMID- 20697463
TI  - Using an audience response system (ARS) in a face-to-face and distance education
      CPT/HCPCS coding course.
AB  - We report the use of an audience response system (ARS) in an undergraduate health
      information management course. The ARS converts a standard PowerPoint
      presentation into an interactive learning system that engages students in active
      participation, and it allows instructors to display questions, surveys, opinion
      polls, and games. We used the ARS in a 2008 course, Health Services Coding, for
      lecture and test reviews. The class consisted of 15 students; nine were on-campus
      students and six were distance education students. All of the responding students
      agreed that the ARS software facilitated learning and made lectures and reviews
      more interesting and interactive, and they preferred taking a class using an ARS.

PMID- 20697464
TI  - Lessons learned from implementation of voice recognition for documentation in the
      military electronic health record system.
AB  - This study evaluated the implementation of voice recognition (VR) for documenting
      outpatient encounters in the electronic health record (EHR) system at a military
      hospital and its 12 outlying clinics. Seventy-five clinicians volunteered to use
      VR, and 64 (85 percent) responded to an online questionnaire post implementation
      to identify variables related to VR continuance or discontinuance. The variables
      investigated were user characteristics, training experience, logistics, and VR
      utility. Forty-four respondents (69 percent) continued to use VR and overall felt
      that the software was accurate, was faster than typing, improved note quality,
      and permitted closing a patient encounter the same day. The discontinuation rate
      of 31 percent was related to location at an outlying clinic and perceptions of
      inadequacy of training, decreased productivity due to VR inaccuracies, and no
      improvement in note quality. Lessons learned can impact future deployment of VR
      in other military and civilian healthcare facilities.

PMID- 20697465
TI  - Family physician perceptions of personal health records.
AB  - The purpose of this qualitative study was to examine family practice physician
      and staff views on the benefits of, barriers to, and use of personal health
      records (PHRs). Four focus groups were conducted at four family medicine
      practices in Iowa and included a total of 28 providers. Overall, participants
      seemed to view PHRs as a source of medical information for healthcare providers
      when the patient's medical record is not available. Providers appeared unaware of
      the patient-centered features available in many electronic PHRs and how such
      features might affect patients and their medical practice. While physicians
      identified numerous patient groups that could benefit from using PHRs, they also
      perceived several unique barriers, including the potential of PHRs to facilitate
      narcotic abuse, low levels of patient computer and health literacy, low levels of
      patient motivation, and difficulties with PHR and electronic medical record
      interoperability. Physicians' relatively narrow view of PHR functions and
      benefits and perception of barriers to using PHRs may restrict widespread support
      of PHR use.

PMID- 20697466
TI  - EHR acceptance factors in ambulatory care: a survey of physician perceptions.
AB  - With the U.S. government calling for electronic health records (EHRs) for all
      Americans by the year 2014, adoption of an interoperable EHR is imminent in
      America's future. However, recent estimates for EHR implementation in the
      ambulatory care environment are just over 10 percent. This second part of a two
      part study examines EHR acceptance factors in an academic-based healthcare
      system. Innovation diffusion theory and the Technology Acceptance Model provide a
      combined theoretical framework for this case study. An online questionnaire was
      administered to 802 faculty, fellow, and resident physicians to explore the
      factors affecting attitudes toward EHR adoption. In this study, age, years in
      practice, clinical specialty, health system relationship, and prior computer
      experience were not predictors of EHR acceptance. In order to facilitate
      successful adoption of health information systems, social and behavioral factors
      must be addressed during the EHR planning phase.

PMID- 20697467
TI  - The effects of innovation factors on smartphone adoption among nurses in
      community hospitals.
AB  - A relatively new mobile technological device is the smartphone-a phone with
      advanced features such as Windows Mobile software, access to the Internet, and
      other computer processing capabilities. This article investigates the decision to
      adopt a smartphone among healthcare professionals, specifically nurses. The study
      examines constructs that affect an individual's decision to adopt a smartphone by
      employing innovation attributes leading to perceived attitudes. We hypothesize
      that individual intentions to use a smartphone are mostly determined by attitudes
      toward using a smartphone, which in turn are affected by innovation
      characteristics. Innovation characteristics are factors that help explain whether
      a user will adopt a new technology. The study consisted of a survey disseminated
      to 200 practicing nurses selected from two community hospitals in the
      southeastern United States. In our model, the innovation characteristics of
      observability, compatibility, job relevance, internal environment, and external
      environment were significant predictors of attitude toward using a smartphone.

PMID- 20697468
TI  - Rural veteran access to healthcare services: investigating the role of
      information and communication technologies in overcoming spatial barriers.
AB  - This multimethod pilot study examined patient and practitioner perspectives on
      the influence of spatial barriers to healthcare access and the role of health
      information technology in overcoming these barriers. The study included a survey
      administered to patients attending a Department of Veterans Affairs (VA) health
      visit, and a focus group with VA care providers. Descriptive results and focus
      group findings are presented. Spatial distance is a significant factor for many
      rural veterans when seeking healthcare. For this sample of rural veterans, a
      range of telephone, computer, and Internet technologies may become more important
      for accessing care as Internet access becomes more ubiquitous and as younger
      veterans begin using the VA health system. The focus group highlighted the
      negative impact of distance, economic considerations, geographic barriers, and
      specific medical conditions on access to care. Lack of adequate technology
      infrastructure was seen as an obstacle to utilization. This study discusses the
      need to consider distance, travel modes, age, and information technology
      infrastructure and adoption when designing health information technology to care
      for rural patients.

PMID- 20697469
TI  - A patient survey assessing the awareness and acceptability of the emergency care
      summary and its consent model in Scotland.
AB  - BACKGROUND: The Emergency Care Summary (ECS) was introduced in 2006 to allow
      aspects of the general practitioner (GP; family doctor, equivalent to primary
      care physician) medical record to be viewed in hospitals and out-of-hours centers
      in Scotland. Records were automatically uploaded unless patients actively opted
      out. This study investigated patient awareness and acceptance of this process.
      METHODS: This was a questionnaire survey of patients in a GP surgery (office) in
      Paisley, Scotland. RESULTS: Survey results indicated that 42 percent of patients
      were aware of the ECS, and 16 percent said that they recognized the leaflet
      posted to households. Of those who recognized the leaflet, 92 percent said they
      were happy for their record to be part of the system, while the others did not
      realize their record was to be included. Having read the leaflet, 97 percent said
      that they were happy for their record to be included in the ECS. CONCLUSIONS:
      This study shows that most patients were not aware of the Emergency Care Summary
      or did not remember seeing the leaflet posted to households. Having read the
      leaflet, the vast majority of patients were happy for their records to be
      included in the system. The low awareness of the ECS calls into question the
      validity of an implied consent model using an information leaflet distributed by
      post.

PMID- 20697470
TI  - Hope for New Jersey's city hospitals: the Camden Initiative.

PMID- 20697471
TI  - Electronic medical record systems in critical access hospitals: leadership
      perspectives on anticipated and realized benefits.
AB  - The growth of electronic medical records (EMRs) is driven by the belief that EMRs
      will significantly improve healthcare providers' performance and reduce
      healthcare costs. Evidence supporting these beliefs is limited, especially for
      small rural hospitals. A survey that focused on health information technology
      (HIT) capacity was administered to all hospitals in Iowa. Structured interviews
      were conducted with the leadership at 15 critical access hospitals (CAHs) that
      had implemented EMRs in order to assess the perceived benefits of operational
      EMRs. The results indicate that most of the hospitals implemented EMRs to improve
      efficiency, timely access, and quality. Many CAH leaders also viewed EMR
      implementation as a necessary business strategy to remain viable and improve
      financial performance. While some reasons reflect external influences, such as
      perceived future federal mandates, other reasons suggest that the decision was
      driven by internal forces, including the hospital's culture and the desires of
      key leaders to embrace HIT. Anticipated benefits were consistent with goals;
      however, realized benefits were rarely obvious in terms of quantifiable results.
      These findings expand the limited research on the rationale for implementing EMRs
      in critical access hospitals.

PMID- 20697472
TI  - Access to cardiac interventional services in Alabama and Mississippi: a
      geographical information system analysis.
AB  - OBJECTIVE: The objective of this study was to determine the contribution of
      distance to hospitals with cardiac interventional services (CIS) to county age
      adjusted myocardial infarction (MI) mortality rates (CAMR) in Alabama and
      Mississippi counties. METHODS: THE STUDY USED THREE DATA SOURCES: U.S. Census
      data, Centers for Disease Control and Prevention (CDC) mortality data, and
      American Hospital Association data. A geographical information system (GIS) was
      used to measure distance, providing an empirical measure of county access to CIS.
      Multiple regression analysis was conducted using measures of distance to CIS,
      county rural status, state, sex, poverty, education, race, and interaction as
      predictors of CAMR. RESULTS: Regression results indicate that the model
      significantly predicts CAMR, R(2) = .378, adjusted R(2) = .319, F = 6.321, p <
      .001. The model accounts for 31.9 percent of the variability. CONCLUSIONS: The
      results of this study do not lead to the conclusion that cardiac outcomes as
      measured by CAMR were sensitive to the geographic location of CIS. However,
      statistically significant interactions supported the sensitivity of CAMR to
      complex patterns and issues of rural status, poverty, education, and race.

PMID- 20697473
TI  - Ethical issues in scientific publication.

PMID- 20697474
TI  - Cartilage repair: A review of Stanmore experience in the treatment of
      osteochondral defects in the knee with various surgical techniques.
AB  - Articular cartilage damage in the young adult knee, if left untreated, it may
      proceed to degenerative osteoarthritis and is a serious cause of disability and
      loss of function. Surgical cartilage repair of an osteochondral defect can give
      the patient significant relief from symptoms and preserve the functional life of
      the joint. Several techniques including bone marrow stimulation, cartilage tissue
      based therapy, cartilage cell seeded therapies and osteotomies have been
      described in the literature with varying results. Established techniques rely
      mainly on the formation of fibro-cartilage, which has been shown to degenerate
      over time due to shear forces. The implantation of autologous cultured
      chondrocytes into an osteochondral defect, may replace damaged cartilage with
      hyaline or hyaline-like cartilage. This clinical review assesses current surgical
      techniques and makes recommendations on the most appropriate method of cartilage
      repair when managing symptomatic osteochondral defects of the knee. We also
      discuss the experience with the technique of autologous chondrocyte implantation
      at our institution over the past 11 years.

PMID- 20697475
TI  - Decal bone matrix as a local antibiotic delivery vehicle in a MRSA-infected bone
      model: An experimental study.
AB  - BACKGROUND: Polymethyl methacrylate (PMMA) antibiotic beads though have proved
      their utility as a local antibiotic delivery system, however, there are
      limitations. Decalcified bone matrix (DBM) as a vehicle of antibiotics can serve
      the purpose, provided a minimum inhibitory concentration is sustained. Healing of
      the defect and avoiding the second surgery is another advantage. We studied the
      DBM as the delivery vehicle for vancomycin in controlling the methicillin
      resistant Staphylococcus aureus (MRSA) osteomyelitis as well as healing of the
      cavity simultaneously in an experimental study. MATERIALS AND METHODS: An in
      vitro study was conducted to optimize vancomycin impregnation in the DBM. For the
      in vivo study, a unicortical defect was created in the metaphysis of the distal
      femur in 18 rabbits. After contaminating the defect with MRSA, rabbits were
      divided into three groups. Group I (eight limbs) received no graft. Defects in
      group II (11 limbs) were filled with plain DBM chips and in group III (14 limbs),
      cavities were implanted with vancomycin-impregnated decal bone chips. Rabbits
      were assessed by clinical, radiological, histological, gross examination and
      bacterial load assay. High Performance Liquid Chromatography HPLC analysis of
      vancomycin in group III was done to assess the concentration in DBM chips.
      RESULTS: In group I, the infection persisted throughout the period of the study.
      Group II showed the fulminated infection at the grafted site with DBM chips
      sequestrating out. Vancomycin-impregnated decal chips in group III did not show
      any sign of infection and eventually incorporated. The bacterial load study
      showed a progressive load change and HPLC revealed an effective antibiotic
      concentration up to 3 weeks in both in vitro and in vivo. CONCLUSION: Decal bone
      chips were effective as the local antibiotic delivery vehicle in preventing the
      MRSA osteomyelitis model. It eluted vancomycin significantly and the graft uptake
      was also excellent. Allogeneic decal grafts eliminated the need for second
      surgery and acted as an excellent delivery vehicle for antibiotics.

PMID- 20697476
TI  - Effect of neurotransmitters and bone marrow cells for neuronal regeneration in
      iatrogenic spinal cord injury: An experimental study.
AB  - BACKGROUND: Spinal cord trauma is a major health problem with associated
      physical, social, economic and psychological sequelae. Despite many advances in
      research and treatment modalities, the pathophysiology of spinal cord injury
      remains unclear, and morbidity and mortality among these patients remain high.
      This experimental study investigates the regenerative cell proliferation effects
      of bone marrow supplemented with neurotransmitters combinations in the
      regeneration of spinal cord injury MATERIALS AND METHODS: Ethical Committee
      Clearance was obtained for animal study. All animal care and procedures were in
      accordance with the CPCSEA and National Institute of Health guidelines. Thirty
      Wistar rats with monoplegia following surgical hemitransection of the spinal cord
      were used for the study. Half of them were randomly selected as the test group
      and the rest as the control group. Spinal cord injury model of Wistar rats in the
      test group were treated by infusing a combination of neurotransmitters and bone
      marrow at the site of injury using a special polythene tube and reservoir for 21
      days. In the control group of rats with monoplegia, normal saline was infused at
      the site of injury for 21 days. The observations are recorded along with results.
      RESULTS: The monoplegia in the test group of rats recovered significantly (P
      value < 0.01) with supplementation of the bone marrow cells and neurotransmitters
      combination. In the control group of rats, there was no recovery. The reward
      seeking locomotor test and sensory recovery test confirmed recovery from spinal
      cord injury in the test group with significance. CONCLUSIONS: The
      neurotransmitters and bone marrow combination was responsible for functional
      recovery in the test group of rats with experimental spinal cord injury We
      believe that the combination of neurotransmitters along with bone marrow may be a
      scope of future research in patients with spinal cord injury.

PMID- 20697477
TI  - Magnetic resonance myelography in early postoperative lumbar discectomy: An
      efficient and cost effective modality.
AB  - BACKGROUND: Magnetic resonance myelography (MRM) after lumbar discectomy is all
      too often an unrewarding challenge. A constellation of findings are inevitable,
      and determining their significance is often difficult. MRM is a noninvasive
      technique that can provide anatomical information about the subarachnoid space.
      Until now, there is no study reported in literature showing any clinico
      radiological correlation of post operative MRM. The objective of this study was
      to prospectively evaluate the diagnostic effectiveness of MRM for the
      demonstration of decompression in operated discectomy patients and its
      correlation with subjective and objective outcome (pain and SLR) in immediate
      postoperative period. MATERIALS AND METHODS: Fifty three patients of single level
      lumbar disc herniation (LDH) justifying the inclusion criteria were operated for
      discectomy. All patients underwent MRM on second/third postoperative day. The
      pain relief and straight leg raise sign improvement was correlated with the
      postoperative MRM images to group the patients into: A- Subjective Pain relief,
      SLR improved and MRM image showing myelo regression; B- Subjective Pain relief,
      SLR improved and MRM image showing no myelo regression; C- No Subjective Pain
      relief, no SLR improved and MRM image showing myelo regression and; D- No
      Subjective Pain relief, no SLR improved and MRM image showing no myelo
      regression. RESULTS: The result showed that Group A had 46 while Group B, C and
      Group D had 4, 2 and one patients respectively. Clinico-radiological correlation
      (Clinically diagnosed patient and findings with MRM correlation) was present in
      47 patients (88.68%) which includes both A and D groups. The MRM specificity and
      sensitivity were 92% and 33.33% respectively. CONCLUSION: MRM is a non-invasive,
      efficient and reliable tool in confirming postoperative decompression in lumbar
      discectomy patients, especially when economic factors are to be considered and
      the required expertise to reliably read a complex confusing post-operative MRI is
      not available readily. Further, controlled double blinded multicentric study in
      operated and non operated LDH, with MRI comparison would give better evidence to
      justify its use in screening to detect persisting compression and to document
      decompression.

PMID- 20697478
TI  - Correlation between clinical features and magnetic resonance imaging findings in
      lumbar disc prolapse.
AB  - BACKGROUND: Lumbar disc prolapse is one of the common causes of low back pain
      seen in the working population. There are contradictorty reports regarding the
      clinical significance of various magnetic resonance imaging (MRI) findings
      observed in these patients. The study was conducted to correlate the
      abnormalities observed on MRI and clinical features of lumbar disc prolapse.
      MATERIALS AND METHODS: 119 clinically diagnosed patients with lumbar disc
      prolapse were included in the study. Clinical evaluation included pain
      distribution, neurological symptoms and signs. MR evaluation included grades of
      disc degeneration, type of herniation, neural foramen compromise, nerve root
      compression, and miscellaneous findings. These MRI findings were tested for inter
      and intraobserver variability. The MRI findings were then correlated with
      clinical symptoms and the level of disc prolapse as well as neurological signs
      and symptoms. Statistical analysis included the Kappa coefficient, Odd's ratio,
      and logistic regression analysis. RESULTS: There were no significant inter- or
      intraobserver variations for most of MRI findings (Kappa value more than 0.5)
      except for type of disc herniation which showed a interobserver variation of 0.46
      (Kappa value). The clinical level of pain distribution correlated well with the
      MRI level (Kappa 0.8), but not all disc bulges produced symptoms. Central bulges
      and disc protrusions with thecal sac compression were mostly asymptomatic, while
      centrolateral protrusions and extrusions with neural foramen compromise
      correlated well with the dermatomal distribution of pain. Root compression
      observed in MRI did not produce neurological symptoms or deficits in all patients
      but when deficits were present, they correlated well with the presence of root
      compression in MRI. Multiple level disc herniations with foramen compromise were
      strongly associated with the presence of neurological signs. CONCLUSIONS: The
      presence of centrolateral protrusion or extrusion with gross foramen compromise
      correlates with clinical signs and symptoms very well, while central bulges and
      disc protrusions correlate poorly with clinical signs and symptoms. The presence
      of neural foramen compromise is more important in determining the clinical signs
      and symptoms while type of disc herniation (bulge, protrusion, or extrusion)
      correlates poorly with clinical signs and symptoms.

PMID- 20697479
TI  - Spinal instability in ankylosing spondylitis.
AB  - BACKGROUND: Unstable spinal lesions in patients with ankylosing spondylitis are
      common and have a high incidence of associated neurological deficit. The
      evolution and presentation of these lesions is unclear and the management
      strategies can be confusing. We present retrospective analysis of the cases of
      ankylosing spondylitis developing spinal instability either due to
      spondylodiscitis or fractures for mechanisms of injury, presentations, management
      strategies and outcome. MATERIALS AND METHODS: In a retrospective analysis of 16
      cases of ankylosing spondylitis, treated surgically for unstable spinal lesions
      over a period of 12 years (1995-2007); 87.5% (n=14) patients had low energy (no
      obvious/trivial) trauma while 12.5% (n=2) patients sustained high energy trauma.
      The most common presentation was pain associated with neurological deficit. The
      surgical indications included neurological deficit, chronic pain due to
      instability and progressive deformity. All patients were treated surgically with
      anterior surgery in 18.8% (n=3) patients, posterior in 56.2% (n=9) patients and
      combined approach in 25% (n=4) patients. Instrumented fusion was carried out in
      87.5% (n=14) patients. Average surgical duration was 3.84 (Range 2-7.5) hours,
      blood loss 765.6 (+/- 472.5) ml and follow-up 54.5 (Range 18-54) months. The
      patients were evaluated for pain score, Frankel neurological grading, deformity
      progression and radiological fusion. One patient died of medical complications a
      week following surgery. RESULTS: Intra-operative adverse events like dural tears
      and inadequate deformity correction occurred in 18.7% (n=3) patients (Cases 6, 7
      and 8) which could be managed conservatively. There was a significant improvement
      in the Visual analogue score for pain from a pre-surgical median of 8 to post
      surgical median of 2 (P=0.001), while the neurological status improved in 90%
      (n=9) patients among those with preoperative neurological deficit who could be
      followed-up (n =10). Frankel grading improved from C to E in 31.25% (n=5)
      patients, D to E in 12.5% (n=2) and B to D in 12.5% (n=2), while it remained
      unchanged in the remaining - E in 31.25% (n=5), B in 6.25% (n=1) and D in 6.25%
      (n=1). Fusion occurred in 11 (68.7%) patients, while 12.5% (n=2) had
      pseudoarthrosis and 12.5% (n=2) patients had evidence of inadequate fusion. 68.7%
      (n=11) patients regained their pre-injury functional status, with no spine
      related complaints and 25% (n=4) patients had complaints like chronic back pain
      and deformity progression. In one patient (6.2%) who died of medical
      complications a week following surgery, the neurological function remained
      unchanged (Frankel grade D). Persistent back pain attributed to inadequate
      fusion/ pseudoarthrosis could be managed conservatively in 12.5% (n=2) patients.
      Progression of deformity and pain secondary to pseudoarthrosis, requiring
      revision surgery was noted in one patient (6.2%). One patient (6.2%) had no
      neurological recovery following the surgery and continued to have nonfunctional
      neurological status. CONCLUSION: In ankylosing spondylitis, the diagnosis of
      unstable spinal lesions needs high index of suspicion and extensive radiological
      evaluation Surgery is indicated if neurological deficit, two/three column injury,
      significant pain and progressive deformity are present. Long segment
      instrumentation and fusion is ideal.

PMID- 20697480
TI  - Femoral neck anteversion, acetabular anteversion and combined anteversion in the
      normal Indian adult population: A computed tomographic study.
AB  - BACKGROUND: Abnormal femoral neck anteversion (FNA) and/or acetabulum anteversion
      (AA) have long been implicated in the etiogenesis of hip osteoarthritis (OA),
      developmental dysplasia of the hip (DDH), and impingement, instability and wear
      in total hip arthroplasty (THA). Since studies on the Indian population are
      sparse on this topic, the purpose of this study was to report the normal values
      of FNA, AA and the combined anteversion (CA= FNA+ AA) in Indian adults. MATERIALS
      AND METHODS: FNA, AA and CA were prospectively measured in 172 normal hips in 86
      Indian adults using standardized computed tomographic (CT) methods and this data
      was compared with the established Western values. RESULTS: The median values and
      interquartile ranges were 8 degrees (6.5-10.0 degrees ) for FNA, 19 degrees (16.0
      22.0 degrees ) for AA and 27 degrees (23.5-30.0 degrees ) for CA. AA and CA
      values were significantly (P<0.05) lower in males, and there was also a trend
      towards lower FNA in males. Although a negative correlation was observed between
      the FNA and AA, this was not strong and may not be clinically relevant.
      CONCLUSION: When compared with the Western data, the FNA values were 3-12 degrees
      lower and the CA values were 3-5 degrees lower in Indian adults. The AA values
      were comparable, but were skewed towards the higher side. Further studies are
      needed to assess the clinical relevance of our basic science data in pathogenesis
      of OA, and to validate it in relation to hip surgeries like corrective
      osteotomies and THA.

PMID- 20697481
TI  - Primary cemented total hip arthroplasty: 10 years follow-up.
AB  - BACKGROUND: Primary cemented total hip arthroplasty is a procedure for non
      traumatic and traumatic affections of the hip. Long term follow-up is required to
      assess the longevity of the implant and establish the procedure. Indo-Asian
      literature on long term result of total hip arthroplasty is sparse. We present a
      10-year follow-up of our patients of primary cemented total hip arthroplasty.
      MATERIALS AND METHODS: We operated 31 hips in 30 patients with primary cemented
      total hip arthroplasty. We followed the cases for a minimum period of 10 years
      with a mean follow-up period of 12.7 years. The mean age of the patients was 60.7
      years (range 37-82 yrs) male to female ratio was 2:1. The clinical diagnoses
      included - avascular necrosis of femoral head (n=15), sero positive rheumatoid
      arthritis (n=5), seronegative spondylo-arthropathy (n=4), neglected femoral neck
      fractures (n=3), healed tubercular arthritis (n=2) and post traumatic
      osteoarthritis of hip (n=2). The prostheses used were cemented Charnley's total
      hip (n=12) and cemented modular prosthesis (n=19). The results were assessed
      according to Harris hip score and radiographs taken at yearly intervals. RESULTS:
      The mean follow-up is 12.7 yrs (range 11-16 yrs) Results in all operated patients
      showed marked improvement in Harris hip score from preoperative mean 29.2 to 79.9
      at 10 years or more followup. However, the non-inflammatory group showed more
      sustained long term improvement as compared to the inflammatory group, as
      revealed by the Harris hip score. Mean blood loss was 450ml (+/-3.7 ml), mean
      transfusion rate was 1.2 units (+/-.3). The complications were hypotension (n=7),
      shortening >1.5 cm (n=9), superficial infection (n=2) and malposition of
      prosthesis (n=1). CONCLUSION: The needs of Indian Asian patients, vary from what
      is discussed in literature. The pain tolerance is greater than western population
      and financial constraints are high. Thus revision surgery among Indian-Asian
      patients is less compared to western yard sticks.

PMID- 20697482
TI  - Intertrochanteric fractures in elderly high risk patients treated with Ender
      nails and compression screw.
AB  - BACKGROUND: Ender and Simon Weidner popularized the concept of closed
      condylocephlic nailing for intertrochanteric fractures in 1970. The clinical
      experience of authors revealed that Ender nailing alone cannot provide secure
      fixation in elderly patients with osteoporosis. Hence we conducted a study to
      evaluate the efficacy of a combined fixation procedure using Ender nails and a
      cannulated compression screw for intertrochanteric fractures. MATERIALS AND
      METHODS: 76 patients with intertrochanteric fractures were treated using
      intramedullary Ender nails and cannulated compression screw from January 2004 to
      December 2007. The mean age of the patients was 80 years (range 70-105
      years).Using the Evan's system of classification 49 were stable and 27 unstable
      fractures. Inclusion criteria was high risk elderly patients (age > 70 years)
      with intertrochanteric fracture. The exclusion criteria included patients with
      pressure sores over the trochanteric region. Many patients had pre-existing co
      morbidities like diabetes mellitus, hypertension, COPD, ischemic heart disease,
      CVA and coronary artery bypass surgery. The two Ender nails of 4.5mm each were
      passed across the fracture site into the proximal neck. This was reinforced with
      a 6.5 mm cannulated compression screw passed from the sub trochanteric region,
      across the fracture into the head. RESULTS: The mean follow-up was 14 months
      (range 9-19 months) Average time to fracture union was 10 weeks (range 6-16
      weeks). The mean knee ROM was 130 degrees (+/- 5 degrees ). There was no case of
      nail penetration into hip joint. In five cases with advanced osteoporosis there
      was minimal migration of Ender nails distally. CONCLUSIONS: The Ender nailing
      combined with compression screw fixation in cases of intertrochanteric fractures
      in high risk elderly patients could achieve reliable fracture stability with
      minimal complications.

PMID- 20697483
TI  - Mini-subvastus approach for total knee arthroplasty in obese patients.
AB  - BACKGROUND: Mini-subvastus approach for Total Knee Arthropalsty allows a faster
      recovery. It is traditionally not utilized for obese patients because of
      difficulty in exposure of the knee and eversion of the patella. We hypothesized
      that obesity should not really cause a problem for patients undergoing a TKA with
      the mini-subvastus approach as the anatomy of the quadriceps in the obese and the
      nonobese patient population is the same. We present an analysis of the use of
      mini-subvastus approach in obese patients. MATERIALS AND METHODS: 97 obese
      patients (109 knees) 81 females + 16 males with mean age 64 years underwent total
      knee arthroplasty (TKA) by mini-subvastus approach between January 2006 to July
      2007. 16 patients (18 kness) were morbidly obese. All patients were prospectively
      evaluated by pre- and postoperative Knee Society and function score. The average
      follow-up was 18 months (range from 1 to 3 years) with minimum 1 year follow-up.
      RESULTS: The approach provided adequate exposure in all knees, with an average
      surgical time of 90 minutes. The patella could be everted easily after the tibial
      and femoral cuts. The average Knee Society score improved from 42 to 89 and the
      function score from 48 to 65. The complications included medial collateral
      ligament injury (one case) and patellar tendon avulsion (one case). CONCLUSION:
      Our results compare favorably with other reported series in obese patients. The
      mini-subvastus approach can be considered in obese patients.

PMID- 20697484
TI  - Total knee arthroplasty: Limb length discrepancy and functional outcome.
AB  - BACKGROUND: Limb length discrepancy and its effects on patient function have been
      discussed in depth in the literature with respect to hip arthroplasty but there
      are few studies that have examined the effect on function of limb length
      discrepency following total knee arthroplasty (TKA). The aim of this study was to
      determine whether limb length discrepancy after TKA in patients with bilateral
      osteoarthritis of knee with varus deformity affects functional outcome. MATERIALS
      AND METHODS: Fifty-four patients with bilateral osteoarthritis of knee with varus
      deformity, who were operated for total knee arthroplasty from 1996 to 2008, were
      reviewed retrospectively. The patients were divided into two groups. Thirty
      patients (mean age 64 years) were operated for unilateral TKA and thirty patients
      (mean age 65.8 years) were operated for bilateral total knee arthroplasty. Six
      patients underwent staged surgery and were included in both groups as the time
      interval between the two surgeries was more than the minimum 6-month follow-up
      period specified for inclusion in the study. The limb length discrepancy was
      measured and statistically correlated with the functional component of the Knee
      Society Score. RESULT: In the unilateral group (n=30), the mean limb length
      discrepancy was 1.53 cm (range: 0-3 cm) and the mean functional score was 73
      (range: 45-100). In the bilateral group (n=30), the mean limb length discrepancy
      was 0.5 cm (range: 0-2 cm) and the mean functional score was 80.67 (range: 0
      100). A statistically significant negative correlation was found between limb
      length discrepancy and functional score in the unilateral group (Spearman
      correlation coefficient, r =-0.52, P=0.006), while no statistically significant
      correlation was found in the bilateral group (Spearman correlation coefficient, r
      = -0.141, P=0.458). CONCLUSION: Limb length discrepancy affects functional
      outcome after total knee arthroplasty, especially so in patients of bilateral
      osteoarthritis with varus deformity undergoing surgery of only one knee.

PMID- 20697485
TI  - Clinical outcomes of arthroscopic single and double row repair in full thickness
      rotator cuff tears.
AB  - BACKGROUND: There has been a recent interest in the double row repair method for
      arthroscopic rotator cuff repair following favourable biomechanical results
      reported by some studies. The purpose of this study was to compare the clinical
      results of arthroscopic single row and double row repair methods in the full
      thickness rotator cuff tears. MATERIALS AND METHODS: 22 patients of arthroscopic
      single row repair (group I) and 25 patients who underwent double row repair
      (group II) from March 2003 to March 2005 were retrospectively evaluated and
      compared for the clinical outcomes. The mean age was 58 years and 56 years
      respectively for group I and II. The average follow-up in the two groups was 24
      months. The evaluation was done by using the University of California Los Angeles
      (UCLA) rating scale and the shoulder index of the American Shoulder and Elbow
      Surgeons (ASES). RESULTS: In Group I, the mean ASES score increased from 30.48 to
      87.40 and the mean ASES score increased from 32.00 to 91.45 in the Group II. The
      mean UCLA score increased from the preoperative 12.23 to 30.82 in Group I and
      from 12.20 to 32.40 in Group II. Each method has shown no statistical clinical
      differences between two methods, but based on the sub scores of UCLA score, the
      double row repair method yields better results for the strength, and it gives
      more satisfaction to the patients than the single row repair method. CONCLUSIONS:
      Comparing the two methods, double row repair group showed better clinical results
      in recovering strength and gave more satisfaction to the patients but no
      statistical clinical difference was found between 2 methods.

PMID- 20697486
TI  - Outcome of early active mobilization after flexor tendons repair in zones II-V in
      hand.
AB  - BACKGROUND: The functional outcome of a flexor tendon injury after repair depends
      on multiple factors. The postoperative management of tendon injuries has paved a
      sea through many mobilization protocols. The improved understanding of splinting
      techniques has promoted the understanding and implication of these mobilization
      protocols. We conducted a study to observe and record the results of early active
      mobilization of repaired flexor tendons in zones II-V. MATERIALS AND METHODS: 25
      cases with 75 digits involving 129 flexor tendons including 8 flexor pollicis
      longus (FPL) tendons in zones II-V of thumb were subjected to the early active
      mobilization protocol. Eighteen (72%) patients were below 30 years of age. Twenty
      four cases (96%) sustained injury by sharp instrument either accidentally or by
      assault. Ring and little finger were involved in 50% instances. In all digits,
      either a primary repair (n=26) or a delayed primary repair (n=49) was done. The
      repair was done with the modified Kessler core suture technique with locking
      epitendinous sutures with a knot inside the repair site, using polypropylene 3
      0/4-0 sutures. An end-to-end repair of the cut nerves was done under loupe
      magnification using a 6-0/8-0 polyamide suture. The rehabilitation program
      adopted was a modification of Kleinert's regimen, and Silfverskiold regimen. The
      final assessment was done at 14 weeks post repair using the Louisville system of
      Lister et al. RESULTS: Eighteen of excellent results were attributed to ring and
      little fingers where there was a flexion lag of < 1 cm and an extension lag of <
      15 degrees . FPL showed 75% (n=6) excellent flexion. 63% (n=47) digits showed
      excellent results whereas good results were seen in 19% (n=14) digits. Nine
      percent (n=7) digits showed fair and the same number showed poor results. The
      cases where the median (n=4) or ulnar nerve (n=6) or both (n=3) were involved led
      to some deformity (clawing/ape thumb) at 6 months postoperatively. The cases with
      digital or common digital nerve involvement (n=7 with 17 digits) showed five
      excellent, two good, four fair, and six poor results. Complications included
      tendon ruptures in 2 (3%) cases (one thumb and one ring finger) and contracture
      in 2 (3%) cases whereas superficial infection and flap necrosis was seen in 1
      case each. CONCLUSION: The early active mobilization of cut flexor tendons in
      zones II-V using the modified mobilization protocol has given good results, with
      minimal complications.

PMID- 20697487
TI  - Skeletal age in idiopathic short stature: An analytical study by the TW3 method,
      Greulich and Pyle method.
AB  - BACKGROUND: The skeletal age in short stature and in various other growth
      abnormalities is well documented. We lack the study pertaining to the analysis of
      the skeletal age in idiopathic short stature or analyzing the difference in
      skeletal age delay or advancement between the familial short stature (FSS) and
      non-familial short stature (non-FSS) groups, hence this study. Present
      retrospective study is designed to study the variation in patterns of skeletal
      age in ISS. MATERIALS AND METHODS: One hundred and eighty six patients, 95 males
      and 91 females of idiopathic short stature were examined to assess the skeletal
      age deviation in relation to chronological age. The radiographs of the left hand
      and wrist were done. The skeletal age was assessed using Tanner and Whitehouse
      (TW3) method and Greulich and Pyle (GP) atlas. The patients were divided into two
      groups based on the parental heights. Group A (Familial Short Stature; FSS) with
      100 patients (55 males, 45 females) included patients whose at least one parent
      was short and Group B (non-Familial Short Stature; non-FSS) with 86 patients (40
      males, 46 females), included patients whose parental height was normal. The
      carpal scores, RUS (Radius, Ulna and Short bone) scores and GP age were
      determined and the respective delay or advances were calculated. RESULTS: The
      skeletal age in Group A was delayed relative to chronological age by a mean of
      1.9 years in males and 2.3 years in females (P<0.05) by RUS method, mean of 2.7
      years in males and 2.6 years in females by Carpal score (P<0.05), 2.2 years in
      males and 2.7 years in females by GP atlas age (P<0.05). The skeletal age in
      Group B was advanced by a mean of 0.9 years in males and 1.4 years in females
      (P<0.05) by RUS method, mean of 0.4 years in males and 0.35 years in females by
      Carpal score (P<0.05), mean of 1.1 years in males and 0.2 years in females by GP
      atlas method (P<0.05). The Pearson's coefficient of correlation (P<.001)
      demonstrated good agreement association between all three scores. CONCLUSIONS:
      There is definite age delay in both males and females in the FSS group while the
      bone maturation is accelerated in the non-FSS group. Both RUS and GP show good
      correlation amongst both the genders in both the groups and there is good inter
      observer correlation for both the methods. We can hypothesize that while
      treatment protocols to accelerate bone age will be beneficial in the FSS group,
      these should be avoided in the non-FSS group. Our study also indicates that there
      definitely exists a difference in normal growth curves in both these groups and a
      detailed study is required to plot their respective normal growth lines so as to
      make proper adjustments in the assessment of the remaining growth and limb
      lengthening protocols.

PMID- 20697488
TI  - Resection-reconstruction arthroplasty for giant cell tumor of distal radius.
AB  - BACKGROUND: Giant cell tumor (GCT) of the distal radius poses problems for
      reconstruction after resection. Several reconstructive procedures like
      vascularized and non-vascularized fibular graft, osteo-articular allograft,
      ceramic prosthesis and megaprosthesis are in use for substitution of the defect
      in the distal radius following resection. Most authors advocate wrist arthrodesis
      following resection of distal radius and non vascularized fibular graft. Here we
      have analyzed the results of aggressive benign GCTs of the distal radius treated
      by resection and reconstruction arthroplasty using autogenous non-vascularized
      fibular graft. MATERIALS AND METHODS: Twenty-four cases of giant cell tumor of
      the distal radius (mean age 32 years, mean follow-up 6.6 years) treated by en
      bloc resection and reconstruction arthroplasty using autogenous non-vascularized
      ipsilateral fibular graft with a minimum followup of two years have been included
      in this retrospective study. Nineteen cases were of Campanacci grade III and five
      were of Grade II recurrence. The mean resected length of the radius was 9.5 (8
      12) cm. Routine radiographs and clinical assessments regarding pain, instability,
      recurrence, hand grip strength and functional status were done at regular
      intervals and functional results were assessed using (musculoskeletal tumor
      society) MSTS-87 scoring. RESULTS: Early radiological union at host-graft
      junction was achieved at mean 12.5 weeks, (range 12-14 weeks) and solid
      incorporation with callus formation was observed in mean 29 weeks (range 28-32
      weeks) in all the cases. Satisfactory range of motion (mean 63%, range 52-78%) of
      the wrist was achieved in 18 cases. Grip strength compared to the contralateral
      hand was found to be 67% (range 58-74%). Functional results were excellent in six
      cases (25%), good in 14 cases (58.3%) and four (16.7%) cases had fair results.
      Soft tissue recurrence was seen in one patient. The most commonly encountered
      complication was fibulo-carpal subluxation (10 cases, 41.7%). CONCLUSION:
      Resection of the distal radius and reconstruction arthroplasty with non
      vascularized proximal fibular graft is useful in preserving the functional
      movement and stability of the wrist as well as achieving satisfactory range of
      movement and grip strength.

PMID- 20697489
TI  - Role of suture anchors in management of fractures of inferior pole of patella.
AB  - BACKGROUND: The traditional recommendation for displaced comminuted inferior pole
      fractures is excision of the comminuted pole followed by reattachment of the
      patellar tendon with transosseous suture. To the best of our knowledge there has
      been no previous published study mentioning the use of suture anchors for
      fracture inferior pole of patella. We present a retrospective analysis of five
      cases of patients doing well at final follow-up of two years. MATERIALS AND
      METHODS: Five patients treated at our institute using suture anchors for repair
      of comminuted inferior pole fractures of patella between January 2007 to March
      2007. (range 28 years-55 years). There were three males and two females. RESULTS:
      The average follow-up was 25 months (range 24 months-26 months). The patients
      were evaluated for range of motion, strength, patellofemoral scores and any
      alteration of patellar height. The outcome of the procedure was assessed with use
      of the patellofemoral scoring system of Noyes et al,5 as adapted by Saltzman et
      al.6 The final patellofemoral score (maximum 100 points) was 94.6 (range 93-96).
      CONCLUSION: We believe it is a novel extended indication of the use of suture
      anchors and should be in the armament of every trauma surgeon.

PMID- 20697490
TI  - Multiple osseous involvements in a case of disseminated cryptococcosis.
AB  - Osseous involvement occurs in 5-10% of patients with disseminated cryptococcosis.
      We are reporting an unusual case of disseminated cryptococcosis involving the
      sternum and lumbar vertebra with the formation of psoas abscess with pulmonary
      tuberculosis. The patient presented with fever for 3 months. A diagnosis of
      pulmonary tuberculosis was made on thoracic contrast-enhanced computerized
      tomography and she was put on antituberculosis treatment. She was immunocompetent
      with negative human immunodeficiency virus. She conceived subsequently and had
      complaints of backache and swelling over the sternum. Magnetic resonance imaging
      showed destruction of L5 vertebra with psoas abscess. Vertebral cryptococcosis
      may mimic tuberculosis and malignancy. She had a bad obstetric history and
      experienced five, first-trimester spontaneous abortions in each successive year
      since 2001. This pregnancy again resulted in spontaneous abortion. Cryptococcus
      neoformans was isolated from two different sites: pus-involving the sternum and
      ultrasound-guided psoas abscess aspirate. Serum latex agglutination test for
      cryptococcal capsular polysaccharide antigen was positive. The diagnosis of
      cryptococcosis was delayed because the patient was diagnosed as a case of
      pulmonary tuberculosis, wherein clinical signs, symptoms and radiological
      findings in both the conditions are similar. Amphotericin B was started but she
      developed varicella infection and expired due to cardiac failure.

PMID- 20697491
TI  - Peripheral primitive neuroectodermal tumor causing cauda equina syndrome with
      destruction of L5 vertebra.
AB  - A 24-year-old male patient presented with cauda equina lesion symptoms. His
      clinicoradiological examination including X-rays, CT scan and MRI revealed
      destruction of L(5) vertebral body, pedicle and a mass extending to lateral
      recess and left intervertebral foramina causing pressure over the thecal sac. A
      CT guided FNAC was inconclusive. Open biopsy and hemilaminectomy of L(5) vertebra
      was performed. Histopathology and immunocytochemical analysis revealed it to be
      primitive neuroectodermal tumor. Patient was given chemotherapy and radiation
      therapy. His lower limb power improved by grade I post operatively and at 2 years
      follow-up bowel/bladder recovery was noticed. Patient died after 2.5 years of
      surgery because of pulmonary metastasis.

PMID- 20697492
TI  - Nora's lesion of the second toe.
AB  - Bizarre parosteal osteochondromatous proliferation, otherwise known as Nora's
      lesion, is surface tumor of bone with high probability of local recurrence. The
      author reports a case of Nora's lesion of the proximal phalanx of the second toe,
      successfully managed by en bloc excision of the swelling. At four-year follow-up
      there was no evidence of recurrence.

PMID- 20697493
TI  - Transstyloid, transscaphoid, transtriquetral perilunate dislocation - A late
      presentation.
AB  - Transstyloid, transscaphoid, transtriquetral perilunate dislocations are
      extremely rare carpal dislocations. We report a 24-year-old male who presented
      with this rare injury pattern four weeks after sustaining trauma. The patient
      underwent open reduction and internal fixation via dorsal approach. Reduction was
      assisted by the use of Joshi's Distraction System. Scaphoid fracture healed by 16
      weeks. At 2 years follow-up patient has good range of motion around wrist without
      any discomfort.

PMID- 20697494
TI  - Spontaneous fusion across the apex of severe thoracolumbar Scheuermann's
      kyphosis: A surgical consideration.
AB  - Considerable debate exists regarding the pathogenesis, natural history and
      treatment of Scheuermann's kyphosis. Surgical correction is indicated in the
      presence of severe kyphosis which carries the risk of neurological complications,
      persistent back pain and significant cosmetic deformity. This can be achieved
      through a posterior-only or an anteroposterior approach. Spontaneous fusion in
      association with Scheuermann's kyphosis has not been previously described. This
      is an important consideration if surgical correction of the kyphosis is planned.
      Two patients with severe thoracolumbar Scheuermann's kyphosis who developed
      spontaneous posterior and anteroposterior fusion across the apex of the deformity
      are presented. The surgical treatment and final outcome is discussed.

PMID- 20697495
TI  - Anthropometric study of hip with computed tomography scan.

PMID- 20697496
TI  - Author's reply.

PMID- 20697497
TI  - Effect of amino acids lysine and arginine on fracture healing in rabbits.

PMID- 20697498
TI  - Epilepsy care in developing countries: part I of II.
AB  - Although 80% of people with epilepsy reside in resource poor, developing
      countries, epilepsy care in these regions remains limited and the majority of
      epilepsy patients go untreated. Cost-effective, sustainable epilepsy care
      services, delivering first-line antiepileptic drugs through established primary
      health care facilities, are needed to decrease these treatment gaps. Neurologists
      with local experience and knowledge of the culture, who are willing to serve as
      educators, policy advisors, and advocates, can make a difference. This is Part I
      of a two-part article. Part I reviews the burden of epilepsy and the current
      state of resources for treatment in developing countries, while Part II (to be
      published in Epilepsy Currents issue 10.5) will provide an "Overview of Care" in
      these countries.

PMID- 20697499
TI  - Are generalized tonic-clonic seizures really "generalized"?

PMID- 20697500
TI  - Urgent continuous EEG (cEEG) monitoring leads to changes in treatment in half of
      cases.

PMID- 20697501
TI  - Wada you do for language: fMRI and language lateralization?

PMID- 20697502
TI  - Operating in the dark ... to see is to cure.

PMID- 20697503
TI  - Point.

PMID- 20697504
TI  - Counterpoint to "what is an epileptic seizure?" by D'Ambrosio and Miller.
AB  - D'Ambrosio and Miller argue that brief (i.e., one to a few seconds), rhythmic
      electrographic events accompanied by behavioral arrest, which they have observed
      in rats after lateral fluid percussion (i.e., in an animal model of traumatic
      brain injury), should be considered seizures in this model of posttraumatic
      epilepsy (1). A counter argument is that these events are not characteristic of
      the seizures seen clinically in posttraumatic epilepsy or in other forms of
      acquired epilepsy. Furthermore, several types of brief, rhythmic activity can be
      recorded in the electroencephalogram (EEG) of animals and humans without
      epilepsy. One cannot exclude the possibility that such events represent normal
      electrical activity, which may (or even may not) occur more often after brain
      injury. Thus, caution is required. In this counterpoint to "What Is an Epileptic
      Seizure?" by D'Ambrosio and Miller, the assertion is made that experimental
      studies on animal models of acquired epilepsy that claim electrographic events to
      be seizures, when the possibility exists that they may not be seizures
      characteristic of human acquired epilepsy, could be counterproductive, since
      research resources could be focused on animal models that may not actually
      demonstrate acquired epilepsy.

PMID- 20697505
TI  - Is neuronal death necessary for acquired epileptogenesis in the immature brain?
AB  - A central question concerning acquired epileptogenesis in the immature brain is
      whether neuronal death is required for the development of epilepsy after a brain
      insult. Results from three different animal models of brain injury during early
      development have been used to develop the hypothesis that status epilepticus,
      prolonged febrile seizures, or hypoxia-induced seizures can lead to chronic
      epilepsy without the occurrence of neuronal death. This brief review will
      summarize the evidence supporting the hypothesis in each model and then critique
      the data and published interpretations. A case will be made that the evidence to
      date neither rules out the occurrence of neuronal death nor demonstrates that
      epileptogenesis (i.e., spontaneous recurrent seizures) has actually occurred in
      these animal models of acquired pediatric epilepsy. We also review evidence for
      the opposing hypothesis: acquired epileptogenesis in the immature brain requires,
      or at least often involves, neuronal death.

PMID- 20697506
TI  - Trekking through the telencephalon: hepatocyte growth factor-mediated guidance
      for parvalbumin-expressing interneurons.

PMID- 20697507
TI  - Responsiveness of ictaform discharges to pharmacotherapy: the bigger they are,
      the harder they fall.

PMID- 20697508
TI  - In support of Canada's health care system: an oncologist's perspective.

PMID- 20697509
TI  - Sunitinib malate for gastrointestinal stromal tumour in imatinib mesylate
      resistant patients: recommendations and evidence.
AB  - QUESTION: Is sunitinib malate-marketed as Sutent (Pfizer Canada, Kirkland, QC)
      superior to placebo or other interventions for primary outcomes of interest in
      adult patients with gastrointestinal stromal tumour (GIST) who have developed
      resistance or who exhibit intolerance to imatinib mesylate (IM)? BACKGROUND: In
      patients with resectable disease, surgery is the mainstay of treatment for GIST;
      in patients with unresectable or metastatic disease, the tyrosine kinase
      inhibitor IM is the therapy of choice. However, some patients have primary
      resistance or intolerance to IM, or they progress after optimal exposure
      (including an escalated dose). Here, we review the evidence for treating IM
      resistant GIST with sunitinib malate. METHODS: Studies of sunitinib malate were
      identified through MEDLINE, EMBASE, the Cochrane Library databases, and Web sites
      of guideline organizations. Outcomes of interest included time to progression,
      progression-free survival, overall survival, and toxicity. RESULTS: One phase III
      randomized controlled trial, and one abstract and presentation describing that
      trial, served as the evidentiary base for this clinical practice guideline. Trial
      data confidently show that both time to progression and progression-free survival
      are highly statistically significant (p < 0.0001) in favour of sunitinib malate
      over placebo. Overall survival was improved with sunitinib malate (hazard ratio:
      0.49; 95% confidence interval: 0.29 to 0.83; p = 0.007; absolute difference in
      weeks not reported). The most frequent of all adverse effects (experienced in
      greater proportion by patients on sunitinib malate) were grades 1 and 2
      leucopenia (52% vs. 5% with placebo), neutropenia (43% vs. 4%), and
      thrombocytopenia (36% vs. 4%). Grade 3 hematologic adverse events were also
      reported more frequently in the sunitinib malate group, including leucopenia (4%
      vs. 0%), neutropenia (8% vs. 4%), lymphopenia (9% vs. 2%), and thrombocytopenia
      (4% vs. 0%). Toxicity comparisons did not include p values. The incidence of
      grades 1-3 fatigue was greater for the sunitinib malate group (34% vs. 22% with
      placebo). Other grade 3 nonhematologic treatment-related adverse events that
      occurred more frequently on sunitinib malate included hand-foot syndrome (4% vs.
      0%), diarrhea (3% vs. 0%), and hypertension (3% vs. 0%). No grade 4 adverse
      events were observed. CONCLUSIONS: In the target population, sunitinib malate is
      the recommended option for second-line therapy of metastatic GIST.

PMID- 20697510
TI  - Access to thalidomide for the treatment of multiple myeloma in Canada: physician
      behaviours and ethical implications.
AB  - BACKGROUND: Multiple myeloma is an incurable malignancy. Since the late 1990s,
      its management has changed with the introduction of novel agents. Thalidomide,
      which is often called a "novel" therapy, has significantly prolonged survival in
      multiple myeloma and is considered worldwide to be part of standard of care in
      this disease. However, thalidomide is not approved in Canada, leading to problems
      with drug access for patients. METHODS: Our study surveyed Canadian hematologists
      on their thalidomide prescribing practices and difficulties with drug access. We
      address some of the ethical issues facing patients and their doctors who are
      unable to obtain or afford the drug, and who therefore resort to alternative
      means such as illegal importation. RESULTS: Of the 411 Canadian hematologists
      contacted, 122 completed the survey, 97 reported that they did not treat myeloma,
      and 192 did not respond. Assuming that all non-responders treat myeloma, our
      estimated overall response rate from physicians who treat this disease was 39%.
      Survey participants indicated that, in Canada, access to thalidomide is a major
      issue for physicians and myeloma patients alike, and that 81% of respondents are
      dissatisfied or very dissatisfied with the drug access process. Many physicians
      felt that the special access process for thalidomide is unduly onerous,
      influences treatment decisions, and invades patient privacy. We found that 20% of
      physicians were unaware of the legal implications of obtaining thalidomide from
      other countries and that at least 23% overtly or covertly support patients in
      obtaining the drug from a non-Health-Canada-approved source. CONCLUSIONS: The
      current lack of access to thalidomide in Canada is a concerning problem for
      patients and health care providers dealing with myeloma. Regulatory changes at
      the federal level (Health Canada) need to be re-examined to promptly resolve this
      issue.

PMID- 20697511
TI  - Optimizing the management of HER2-positive early breast cancer: the clinical
      reality.
AB  - Breast cancer positive for HER2 (human epidermal growth factor receptor 2) is
      associated with a poor prognosis for patients with both early-stage and
      metastatic breast cancer. Trastuzumab has been shown to be effective and is now
      considered the standard of care for early-stage patients with HER2-positive
      breast cancer. In that population, trastuzumab has been studied in six randomized
      clinical trials. Overall, use of this agent leads to a significant reduction in
      risk of disease recurrence and improvement in overall survival. Despite the
      strong evidence for the use of trastuzumab in managing HER2-positive early breast
      cancer (EBC), a number of clinical controversies remain. The authors of this
      paper undertook a review of the available scientific literature on adjuvant
      trastuzumab to produce practical considerations from Canadian oncologists. The
      panel focused their discussion on five key areas: Management of node-negative
      disease with tumours 1 cm or smaller in size. Management of HER2-positive EBC
      across the spectrum of the disease (that is, nodal and steroid hormone receptor
      status, tumour size) Timing of trastuzumab therapy with chemotherapy for early
      stage disease: concurrent or sequential. Treatment duration of trastuzumab for
      EBC. The role of non-anthracycline trastuzumab-based regimens.

PMID- 20697512
TI  - Adjuvant chemoradiation for gastric cancer with infusional 5-fluorouracil and
      cisplatin: a phase I study.
AB  - OBJECTIVE: This phase I study aimed to determine the maximal tolerated dose of
      cisplatin administered every 2 weeks with infusional 5-fluorouracil (5FU) and
      concurrent radiation therapy (RT) in patients after complete resection of gastric
      adenocarcinoma. METHODS: Patients with resected stage IB to IV (M0) gastric
      adenocarcinoma were treated with 12 weeks of infusional 5FU (200 mg/m(2) daily)
      and with RT (45 Gy in 25 fractions starting on day 16). Cisplatin was
      administered in escalating doses (0, 20, 30, and 40 mg/m(2)) in weeks 1, 3, 5,
      and 7. In the final cohort, patients received an additional dose of cisplatin (40
      mg/m(2)) in week 9. RESULTS: Among the 34 patients [median age: 56 years (range:
      31-77 years)] who were assessable for toxicity, 5 experienced dose-limiting
      toxicities: 1 sepsis (cohort 1), 1 fatigue (cohort 2), 3 upper gastrointestinal
      toxicity (1 in cohort 2, 2 in cohort 5). Cohort 5 exceeded the maximal tolerated
      dose. Median follow-up was 2.5 years (range: 0.3-5 years). The 3-year overall and
      relapse-free survival rates were 86% and 71% respectively; median survival was
      not reached. CONCLUSIONS: Cisplatin was well tolerated in combination with
      infusional 5FU and RT, showing promising activity in the adjuvant treatment of
      gastric cancer. Infusional 5FU 200 mg/m(2) daily for 12 weeks with cisplatin 40
      mg/m(2) in weeks 1, 3, 5, and 7 and with concurrent RT 45 Gy in 25 fractions,
      starting at day 16, is being explored in a phase II study at our institution.

PMID- 20697513
TI  - Incidence of taxane-induced pain and distress in patients receiving chemotherapy
      for early-stage breast cancer: a retrospective, outcomes-based survey.
AB  - INTRODUCTION: With the widespread use of sequential anthracycline/taxane-based
      chemotherapy for early-stage breast cancer, clinicians are becoming rapidly aware
      of toxicities associated with those regimens. Despite the low incidence reported
      in the literature of significant arthralgia and myalgia with those regimens, it
      is clinically evident that a substantial proportion of patients develop such
      toxicities. We performed a pilot study to investigate the extent of this problem.
      PATIENTS AND METHODS: Patients who had received prior adjuvant or neoadjuvant
      chemotherapy [doxorubicin-cyclophosphamide followed by paclitaxel (AC-T),
      doxorubicin-cyclophosphamide followed by docetaxel (AC-D), or 5-fluourouracil
      epirubicin-cyclophosphamide followed by docetaxel (FEC-D)] completed a
      retrospective outcomes-based survey. The survey utilized the Functional
      Assessment of Cancer Therapy-Taxane Scale, the Memorial Symptom Assessment Scale,
      and a modified Brief Pain Inventory. RESULTS: Interviews were conducted with 82
      patients. Interviewees had received AC-T (43%), FEC-D (43%), and AC-D (14%). Pain
      as a side effect of either the anthracycline or the taxane chemotherapy was
      reported by 87% of patients. Most of the patients (79%) indicated that their
      worst pain occurred during the taxane component of treatment. Compared with
      paclitaxel, docetaxel was reported to cause more pain. Narcotics for pain
      management were required by 35 of 82 patients (43%). CONCLUSIONS: A significant
      number of patients receiving sequential anthracycline/taxane-based chemotherapy
      for early-stage breast cancer experience pain, particularly during the taxane
      component. Prospective patient-reported outcome assessments are needed to help
      individualize treatment interventions and to improve symptom management in this
      population.

PMID- 20697514
TI  - Cetuximab in locally advanced head-and-neck cancer: defining the population.
AB  - Encouraging data for targeted therapy in head-and-neck squamous cell carcinoma
      are opening new options for treatment. Phase III trials of cetuximab, an antibody
      directed against the epidermal growth factor receptor (EGFR) have demonstrated
      benefit in the locally advanced and metastatic settings. Recognizing the
      importance of emerging therapies, Cancer Care Ontario published guideline
      recommendations for EGFR-targeted therapy in stage III and IV head-and-neck
      cancer. The present paper takes a further look at the population for whom an
      offer of cetuximab therapy may be appropriate.

PMID- 20697515
TI  - The predictive value of pre-treatment inflammatory markers in advanced non-small
      cell lung cancer.
AB  - BACKGROUND: Accurate prediction of outcome in advanced non-small-cell lung cancer
      (NSCLC) remains challenging. Even within the same stage and treatment group,
      survival and response to treatment vary. We set out to determine the predictive
      value of inflammatory markers C-reactive protein (CRP) and white blood cells
      (WBCS) in patients with advanced NSCLC. PATIENTS AND METHODS: Patients were
      assigned a prognostic index (PI): 0 for crp 10 mg/L or less and WBCS 11x109/L or
      less, 1 if one of the two markers was elevated, and 2 if both markers were
      elevated. We then used chest computed tomography (CT) imaging to evaluate
      response after 2 cycles of chemotherapy treatment. RESULTS: Of 134 patients, 46
      had a PI of 0; 60, a PI of 1; and 28, a PI of 2. Disease progressed in 41
      patients. Progression was significantly more frequent among patients with a PI of
      2 (p = 0.008). Median survival was 20.0 months for the PI 0 group, 10.4 months
      for the PI 1 group, and 7.9 months for the PI 2 group (p < 0.001). The PI was the
      only significant prognostic factor for survival even after adjustment for
      performance status, smoking, and weight loss (hazard ratio: 1.57; 95% confidence
      interval: 1.2 to 2.14; p = 0.004). CONCLUSIONS: Inflammatory state correlates
      significantly with both chemotherapy response and survival in stage IV NSCLC. The
      PI may provide additional guidance for therapeutic decision-making.

PMID- 20697516
TI  - A case for tobacco content regulation by the U.S. Food and Drug Administration.
AB  - Although many people welcome the recent move by the United States to give its
      Food and Drug Administration (FDA) the authority to regulate the content of
      tobacco, some worry that such regulation constitutes unwarranted interference
      with the freedom of competent adult tobacco consumers. The concern for protecting
      the autonomy of individuals is valuable indeed, but given the highly addictive
      nature of tobacco products (and especially the nicotine in tobacco products), the
      continued use of tobacco by smokers cannot -without straining credulity-be said
      to be autonomous. This fact, combined with a proper construal of the FDA's role
      and an appreciation of the substantial morbidity and mortality associated with
      tobacco use, makes a strong case for content regulation.

PMID- 20697517
TI  - Weathering storms: a cohort study of how participation in a mindfulness-based
      stress reduction program benefits women after breast cancer treatment.
AB  - INTRODUCTION: A growing number of psychosocial interventions are being offered to
      cancer patients during and after their medical treatment. Here, we examined
      whether Mindfulness-Based Stress Reduction (MBSR), a stress management course,
      helps women to cope better with stress and illness once their breast cancer
      treatment is completed. Our aim was to understand how MBSR may benefit those who
      participate in the course. METHODS: Our cohort study enrolled 59 women in an 8
      week MBSR program. They completed "before and after" questionnaires pertaining to
      outcomes (stress, depression, medical symptoms) and process variables
      (mindfulness, coping with illness, sense of coherence). Paired t-tests examined
      changes from before to after the MBSR course. Changes in mindfulness were
      correlated with changes in post-MBSR variables, and a regression analysis
      examined which variables contributed to a reduction in stress after program
      participation. RESULTS: Adherence to the program was 91%. Participants reported
      significant reductions in stress (p < 0.0001), depression (p < 0.0001), and
      medical symptoms (p < 0.0001), and significant improvements in mindfulness (p <
      0.0001), coping with illness (p < 0.0001), and sense of coherence (p < 0.0001).
      Changes in mindfulness were significantly related to changes in depression,
      stress, emotional coping, and sense of coherence. Increases in mindfulness and
      sense of coherence predicted reductions in stress. CONCLUSIONS: It appears that
      learning how to be mindful is beneficial for women after their treatment for
      breast cancer.

PMID- 20697518
TI  - Dedifferentiated giant cell tumour of bone in the form of low-grade fibroblastic
      osteogenic sarcoma: case report of a unique presentation with follow-up.
AB  - Giant cell tumour (GCT) of bone is a locally aggressive benign tumour. It can,
      however, undergo dedifferentiation, either de novo or secondarily after local
      recurrence or radiation. Whether spontaneously occurring or induced by previous
      irradiation, this malignant transformation is typically defined as a high-grade
      anaplastic sarcoma devoid of giant cells. Dedifferentiation of GCT into low-grade
      appearing sarcoma has not been reported yet. Here, we describe the first case of
      dedifferentiated GCT in the appearance of low-grade fibroblastic osteogenic
      sarcoma with distant bone metastases. This disease progression occurred without
      previous irradiation. We confirm the aggressive behaviour of this tumour despite
      the deceptively bland appearance of the malignant component. We also alert others
      to the importance of recognizing this rare histology to avoid underdiagnosis and
      subsequent undertreatment.

PMID- 20697519
TI  - Evaluating the impact on quality of life of chemoradiation in gastric cancer.
AB  - OBJECTIVE: Our phase I study prospectively evaluated quality of life (QOL) in
      patients undergoing adjuvant chemoradiation for gastric adenocarcinoma. METHODS:
      Thirty-three patients receiving radiotherapy (45 Gy in 25 fractions), together
      with 12 weeks of infusional 5-fluorouacil and escalating doses of cisplatin every
      2 weeks, completed the European Organisation for Research and Treatment of Cancer
      Quality of Life Questionnaire C30 at five time points: baseline, completion of
      radiation, 4 weeks after completion of radiation, 6-12 months after completion of
      chemoradiation, and 2-3 years after completion of chemoradiation. RESULTS: Mean
      age of the patients was 56 years (range: 31-77 years); 55% of the patients were
      male. Median follow-up was 2.7 years (range: 0.3-5 years). The 3-year overall
      survival was 83%. Five patients experienced dose-limiting toxicity (DLT). Median
      scores on global QOL and on the social, role, emotional, nausea and vomiting, and
      fatigue scales showed clinically and statistically significant worsening at
      completion of radiation. Statistical but not clinical worsening was found for the
      physical and appetite scales. By 6-12 months, no subscale showed a difference, on
      average, from the baseline score. However, up to 45% of the patients remained
      below baseline on at least 1 subscale. Patients with DLT had worse scores on the
      emotional and the nausea and vomiting scales. Scores for global QOL and for
      nausea and vomiting were significantly associated with chemotherapy dose.
      CONCLUSIONS: During chemoradiation, QOL is impaired. Although most scores return
      to baseline, recovery may take 6-12 months, and subscale scores remain below
      baseline in a significant proportion of patients.

PMID- 20697520
TI  - Exploring cancer treatment decision-making by patients: a descriptive study.
AB  - OBJECTIVE: Using an interview-guided survey, our descriptive study aimed to
      document the extent to which cancer patients perceive they are involved in making
      treatment decisions and the factors that influence patient involvement. PATIENTS
      AND METHODS: Our study enrolled patients from a Canadian ambulatory oncology
      program who were undergoing chemotherapy or radiation therapy, or both, for
      cancer. The adapted Control Preferences Scale was used to survey perceived and
      preferred roles in decision-making. The study survey also included items from the
      Decisional Conflict Scale and the Preparation for Decision-Making Scale. RESULTS:
      Of 192 participants, 98 (51%) perceived that they were offered treatment choices.
      Of those 98, 47 (48%) thought that the options were presented equally. Compared
      with the patients not offered choices, those who were given choices were less
      passive (4% vs. 29%, p < 0.001) and more satisfied (100% vs. 95%, p < 0.03) in
      decision-making. Participants whose preferred and perceived roles were different
      would have preferred more involvement in decision-making. To attain the preferred
      involvement, patients wanted to receive more information on treatment options, to
      be given a choice, to have more discussion with the health care team, and to have
      providers better listen to their needs. CONCLUSIONS: Only half of surveyed
      patients thought that they were offered choices for their cancer treatment. When
      offered choices, patients were more active in decision-making. Further
      initiatives are required to determine approaches for supporting patients with
      cancer so that they can be more involved in decision-making.

PMID- 20697522
TI  - Radiation recall dermatitis with azithromycin.
AB  - Radiation recall is a well-known phenomenon that involves the "recall" of an
      acute inflammatory reaction in a previously irradiated region after
      administration of certain drugs. The most common type of radiation recall is
      radiation recall dermatitis, which involves the reoccurrence of an acute
      inflammatory skin reaction in previously irradiated skin. Most radiation recall
      reactions are attributable to chemotherapeutic agents. One previously reported
      case of radiation recall dermatitis occurred after administration of an
      antibiotic. The present case report is the second of radiation recall dermatitis
      involving an antibiotic: azithromycin.

PMID- 20697521
TI  - Prophylaxis and management of acute radiation-induced skin reactions: a
      systematic review of the literature.
AB  - Radiation therapy is a common treatment for cancer patients. One of the most
      common side effects of radiation is acute skin reaction (radiation dermatitis)
      that ranges from a mild rash to severe ulceration. Approximately 85% of patients
      treated with radiation therapy will experience a moderate-to-severe skin
      reaction. Acute radiation-induced skin reactions often lead to itching and pain,
      delays in treatment, and diminished aesthetic appearance-and subsequently to a
      decrease in quality of life. Surveys have demonstrated that a wide variety of
      topical, oral, and intravenous agents are used to prevent or to treat radiation
      induced skin reactions. We conducted a literature review to identify trials that
      investigated products for the prophylaxis and management of acute radiation
      dermatitis. Thirty-nine studies met the pre-defined criteria, with thirty-three
      being categorized as prophylactic trials and six as management trials.For
      objective evaluation of skin reactions, the Radiation Therapy Oncology Group
      criteria and the U.S. National Cancer Institute Common Toxicity Criteria were the
      most commonly used tools (65% of the studies). Topical corticosteroid agents were
      found to significantly reduce the severity of skin reactions; however, the trials
      of corticosteroids evaluated various agents, and no clear indication about a
      preferred corticosteroid has emerged. Amifostine and oral enzymes were somewhat
      effective in preventing radiation-induced skin reactions in phase II and phase
      III trials respectively; further large randomized controlled trials should be
      undertaken to better investigate those products. Biafine cream (Ortho-McNeil
      Pharmaceuticals, Titusville, NJ, U.S.A.) was found not to be superior to standard
      regimes in the prevention of radiation-induced skin reactions (n = 6).In
      conclusion, the evidence is insufficient to support the use of a particular agent
      for the prevention and management of acute radiation-induced skin reactions.
      Future trials should focus on comparing agents and approaches that, in phase I
      and II trials, suggest efficacy. These future phase III randomized controlled
      trials must clearly distinguish between preventive and management strategies for
      radiation-induced dermatitis. Only then can evidence-based guidelines be
      developed, with the hope of standardizing the approach across centres and of
      improving the prevention and management of radiation-induced dermatitis.

PMID- 20697523
TI  - Severe Raynaud syndrome induced by adjuvant interferon alfa in metastatic
      melanoma.
AB  - Melanoma is the most lethal form of skin malignancy because of its aggressive
      behaviour. In advanced disease, interferon alfa can be used as adjuvant therapy.
      However, this therapy is not free of side effects. We present a case of severe
      Raynaud syndrome and digital necrosis induced by interferon alfa in a patient
      with melanoma. Pathogenic mechanisms are discussed.

PMID- 20697524
TI  - Aplastic anemia with concurrent temozolomide treatment in a patient with
      glioblastoma multiforme.
AB  - Temozolomide (TMZ) is an oral alkylating agent used during concurrent and
      adjuvant chemotherapy for newly diagnosed glioblastoma multiforme. Temozolomide
      is generally well tolerated and improves survival; however, severe adverse events
      have occasionally been reported. Here, we report the case of a patient who
      developed aplastic anemia with related complications in the setting of concurrent
      TMZ treatment with radiotherapy. This case illustrates that aplastic anemia is a
      rare side effect of TMZ that can occur relatively early in the course of
      concurrent chemotherapy, and underscores the importance of clinician awareness of
      this potentially devastating side effect.

PMID- 20697525
TI  - Malignant melanoma metastatic to the larynx: treatment and functional outcome.
AB  - The review considers management strategies for malignant melanoma metastatic to
      the larynx. This rare clinical entity lacks clear treatment recommendations
      because extirpative surgery can often result in severe functional debilitation in
      patients with limited life expectancy. Here, we report a case of melanoma
      metastatic to the larynx in a patient with a prior history of Hodgkin lymphoma.
      The patient was treated with partial laryngectomy and local radiation therapy.
      The rationale for treatment decisions and for surgical and radiotherapeutic
      techniques and the associated literature are discussed.

PMID- 20697526
TI  - Ductal carcinoma in situ in a 25-year-old man presenting with apparent unilateral
      gynecomastia.
AB  - Ductal carcinoma in situ (DCIS) in a young man is rarely reported. Our patient, a
      25-year-old man, presented with apparent symptomatic unilateral gynecomastia. He
      has a strong history of cancer on both the maternal and paternal sides of his
      family, including breast and lung (maternal) and melanoma, colon, and pancreatic
      (paternal). His mother tested negative for BRCA1 and BRCA2. There is no
      information on paternal genetic testing.The patient was treated with left
      subcutaneous mastectomy. Upon histologic review of the sample, concurrent
      gynecomastia and DCIS were discovered. To date, only 4 cases of gynecomastia and
      DCIS have been described in younger male patients. Because only 30%-50% of
      patients with DCIS eventually develop invasive cancer in the subsequent 10-20
      years, DCIS prevalence in the general population may be higher than predicted.
      This case underscores the importance of family history in any patient presenting
      with a breast mass. Patients must be made aware of the risk, however small it may
      be, and physicians must remain cautious of cancer in young men with gynecomastia.

PMID- 20697527
TI  - Targeting DNA damage and repair by curcumin.
AB  - Curcumin is a compound with anti-tumor effects in a tolerable dose. A recent
      paper by Rowe et al described that curcumin induced DNA damage in triple negative
      breast cancer cells and regulated BRCA1 protein expression and modification.1
      Related research and potential use of curcumin will be discussed in this article.

PMID- 20697528
TI  - Analysis of the relationship between diet and exercise beliefs and actual
      behaviors among breast cancer survivors in northwest ohio.
AB  - INTRODUCTION: Studies have shown that a diet high in fruit and vegetable intake,
      as well as a routine including daily exercise or physical activity, can
      independently affect relapse rates and survivorship in breast cancer patients.
      Fruits and vegetables contain powerful anti-oxidant molecules, capable of
      preventing tumor formation and proliferation. Exercise can lower circulating
      levels of estrogen, the female hormone responsible for tumor proliferation in the
      estrogen-sensitive form of the disease. The most beneficial results have been
      shown in women who exercise and consume a diet rich in fruits and vegetables. We
      studied the attitudes towards and behaviors related to fruit and vegetable intake
      and exercise in a cohort of breast cancer survivors in northwest Ohio. MATERIALS
      AND METHODS: Data were gathered from a survey sent out by the Northwest Ohio
      Branch of the Susan G. Komen For the Cure Foundation. We assessed and evaluated
      survivors' self-reported beliefs, attitudes, and behaviors regarding exercise and
      fruit and vegetable intake. RESULTS: Nearly half of the survivors (46.5%)
      reported being unsure or in disagreement with the statement "Eating at least 5
      servings of fruits and/or vegetables per day will reduce the risk of breast
      cancer recurrence." Only 46.8% of those in agreement with the previous statement
      actually report eating at least 5 fruits and/or vegetables per day. With respect
      to exercise, 32.9% reported being unsure or in disagreement with the statement
      "Engaging in regular physical activity will reduce the risk of breast cancer
      recurrence." Only 68.5% of those in agreement with the previous statement report
      any physical activity in the past 30 days. CONCLUSIONS: Many breast cancer
      survivors do not appear to be aware of the benefits of diet and exercise.
      Further, a large proportion of those who are aware of the benefits do not adapt a
      healthy diet and exercise as part of their lifestyle. A majority of these
      survivors see a primary care physician, which we believe is the best venue to
      bridge this education gap. It is apparent by the pattern our data shows that more
      needs to be done to educate breast cancer survivors about the benefits of
      exercise and fruit and vegetable intake. Steps need to be taken to ensure that
      those who are educated also remain motivated to engage in a healthy lifestyle
      with the hopes of avoiding breast cancer recurrence.

PMID- 20697529
TI  - Detection of Provasopressin in Invasive and Non-invasive (DCIS) Human Breast
      Cancer Using a Monoclonal Antibody Directed Against the C-terminus (MAG1).
AB  - The provasopressin protein (proAVP) is expressed by invasive breast cancer and
      non-invasive breast cancer, or ductal carcinoma in situ (DCIS). Here we
      demonstrate the ability of the monoclonal antibody MAG1 directed against the C
      terminal end of proAVP to identify proAVP in all cases examined of human invasive
      cancer and DCIS (35 and 26, respectively). Tissues were chosen to represent a
      relevant variation in tumor type, grade, patient age, and menopausal status. By
      comparison, there was 65% positive staining for estrogen receptor, 61% for
      progesterone receptor, 67% for nuclear p53, and 39% for c-Erb-B2 with the
      invasive breast cancer sections. Reaction with the normal tissue types examined
      (67) was restricted to the vasopressinergic magnocellular neurons of the
      hypothalamus, where provasopressin is normally produced, and the posterior
      pituitary, where these neurons terminate. The breast epithelial tissue sections
      on the tissue microarray did not react with MAG1. Previously, we demonstrated
      that polyclonal antibodies to proAVP detected that protein in all breast cancer
      samples examined, but there was no reaction with breast tissue containing
      fibrocystic disease. The results presented here not only expand upon those
      earlier results, but they also demonstrate the specificity and effectiveness of
      what may be considered a more clinically-relevant agent. Thus, proAVP appears to
      be an attractive target for the detection of invasive breast cancer and DCIS, and
      these results suggest that MAG1 may be a beneficial tool for use in the
      development of such strategies.

PMID- 20697530
TI  - Does race affect outcomes in triple negative breast cancer?
AB  - BACKGROUND: There is discordance among studies assessing the impact of race on
      outcome of patients with Triple Negative Breast Cancer (TNBC). We assessed
      survival outcomes for African American (AA) versus Caucasian (CA) women with TNBC
      treated at an urban cancer center in Memphis, TN with a predominant AA patient
      population. METHODS: Patients with Stage I-III TNBC were identified from our
      breast database. Event free survival (EFS) and Breast cancer specific survival
      (BCSS) were the primary outcome measures. Cox proportional hazards models were
      fitted for EFS and BCSS. RESULTS: Of the 124 patients, 71% were AA. No
      significant association between race and stage (P = 0.21) or menopausal status (P
      = 0.15) was observed. Median age at diagnosis was significantly lower for AA
      versus CA women (49.5 vs. 55 years, P = 0.024). 92% of the patients received
      standard neo/adjuvant chemotherapy, with no significant difference in duration
      and type of chemotherapy between the races. With a median follow up of 23 months,
      28% of AA vs. 19% of CA women had an event (P = 0.37). 3 year EFS and BCSS
      trended favorably towards CA race (77% vs. 64%, log rank P = 0.20 and 92% vs.
      76%, P = 0.13 respectively) with a similar trend noted on multiple variable
      modeling (EFS: HR 0.62, P = 0.29; BCSS: HR 0.36, P = 0.18). AA women >/=50 years
      at diagnosis had a significantly worse BCSS than the CA women in that age group
      (P = 0.012). CONCLUSION: Older AA women with TNBC have a significantly worse
      breast cancer specific survival than their CA counterparts. Overall, there is a
      trend towards lower survival for AA women compared to Caucasians despite
      uniformity of tumor phenotype and treatment. The high early event rate,
      irrespective of race, underscores the need for effective therapies for women with
      TNBC.

PMID- 20697531
TI  - The Expression Patterns of ER, PR, HER2, CK5/6, EGFR, Ki-67 and AR by
      Immunohistochemical Analysis in Breast Cancer Cell Lines.
AB  - The molecular classification for breast carcinomas has been used in clinical
      studies with a simple surrogate panel of immunohistochemistry (IHC) markers. The
      objective of this current project was to study the molecular classification of
      commonly used breast cancer cell lines by IHC analysis. Seventeen breast cancer
      cell lines were harvested, fixed in formalin and made into cell blocks. IHC
      analyses were performed on each cell block with antibodies to estrogen receptor
      (ER), progesterone receptor (PR), HER2, EGFR, CK5/6, Ki-67 and androgen receptor
      (AR). Among the 17 cell lines, MCF-7 and ZR-75-1 fell to Luminal A subtype; BT
      474 to Luminal B subtype; SKBR-3, MDA-MD-435 and AU 565 to HER2 over-expression
      subtype; MDA-MB-231, MCF-12A, HBL 101, HS 598 T, MCF-10A, MCF-10F, BT-20, 468 and
      BT-483 to basal subtype. MDA-MB-453 belonged to Unclassified subtype. Since each
      subtype defined by this IHC-based molecular classification does show a distinct
      clinical outcome, attention should be paid when choosing a cell line for any
      study.

PMID- 20697532
TI  - Apolipoprotein E Allelic Frequency Altered in Women with Early-onset Breast
      Cancer.
AB  - Among women, the most prevalent type of cancer is breast cancer, affecting 1 out
      of every 8 women in the United States; in Puerto Rico, 70 out of every 100,000
      will develop some type of breast cancer. Therefore, a better understand of the
      potential risk factors for breast cancer could lead to the development of early
      detection tools. A gene that has been proposed as a risk factor in several
      populations around the world is Apolipoprotein E (apoE). ApoE functions as a
      mechanism of transport for lipoproteins and cholesterol throughout the body, with
      3 main isoforms present in humans (apoE2, apoE3, and apoE4). Whether or not apoE4
      is a risk factor for breast cancer remains controversial. Previous studies have
      either included test subjects of all ages (20-80) or have focused on late-onset
      (after age 50) breast cancer; none has concentrated specifically on early-onset
      (aged 50 and younger) breast cancer. The objectives of this study was to examine
      (in a Puerto Rican population) the differences in the relative frequency of
      occurrence of apoE4 in non-breast cancer versus breast cancer patients and to
      examine, as well, the potential differences of same in early- versus late-onset
      patients. We found an increased frequency of apoE4 (odds ratio 2.15) only in
      early-onset breast cancer survivors, which is similar to the findings of those
      studies that combined or adjusted for age as well as for an association between
      apoE4 and decreased tumor size. ApoE is also a potential risk factor for long
      term cognitive effects after chemotherapy and affects response to hormone
      replacement. Our data supports the theory that knowing the apoE genotype of women
      who are at risk of developing breast cancer may be beneficial, as such knowledge
      would aid in the prediction of tumor size and the development of treatment
      regimens.

PMID- 20697546
TI  - President's address. Common mechanisms of multiple diseases: why vegetables and
      exercise are good for you.

PMID- 20697547
TI  - Leveraging learning from a phase III colorectal cancer clinical trial: outcomes,
      methodology, meta-analysis and pharmacogenetics.
AB  - This paper summarizes the results of a National Cancer Institute (NCI) sponsored
      Phase III clinical trial led by the North Central Cancer Treatment Group (NCCTG)
      that enrolled patients with metastatic colorectal cancer (MCRC) on combination
      chemotherapy regimens in the late 1990s through 2003. The study changed clinical
      practice in the US and led to a new Food and Drug Agency (FDA) indication for the
      drug oxaliplatin. The time was opportune in the management of MCRC, when, after
      50 years of using the single active agent 5-Fluorouracil (5-FU), two new
      cytotoxic agents, irinotecan and oxaliplatin, were found to be active in MCRC.
      Patients were randomized to receive two of those three agents in each arm of the
      trial. Over 500 of the >1700 enrolled patients permitted their germline DNA and
      plasma samples to be banked. Consequently this is one of the largest cancer
      populations available for pharmacogenetic studies and for the study of other
      biomarkers. Data derived from N9741 led to publications related to treatment of
      MCRC and trial methodology, used pooled meta-analyses and helped to pioneer the
      field of pharmacogenetics. This review highlights some of those observations.
      Initiated in 1997, the trial has spawned 26 published or in press papers and 39
      abstracts.

PMID- 20697548
TI  - Innate immunity in the adult mammalian heart: for whom the cell tolls.
AB  - Recent studies suggest that the heart possesses an intrinsic system that is
      intended to delimit tissue injury, as well as orchestrate homoeostatic responses
      within the heart. The extant literature suggests that this intrinsic stress
      response is mediated, at least in part, by a family of pattern recognition
      receptors that belong to the innate immune system, including CD14, the soluble
      pattern recognition receptor for lipopolysaccharide, and Toll like receptors-2,
      3, 4, and 6. Although this intrinsic stress response system provides a short-term
      adaptive response to tissue injury, the beneficial effects of this
      phylogenetically ancient system may be lost if myocardial expression of these
      molecules either becomes sustained and/or excessive, in which case the salutary
      effects of activation of these pathways may be contravened by the known
      deleterious effects of inflammatory signaling. Herein we present new information
      with regard to activation of innate immune gene expression in the failing human
      heart. Taken together, these new observations provide provisional evidence that
      the innate immune system is activated in human heart failure, raising the
      interesting possibility that this pathway may represent a target for the
      development of novel heart failure therapeutics.

PMID- 20697549
TI  - "Old" hearts and arteries: the role of oxidative stress.
AB  - Despite decades of investigation, the roles of reactive oxygen species (ROS) in
      atherosclerosis and aging have yet to be defined. We have developed mouse models
      that allow this question to be addressed experimentally. Given the increase in
      risk factors for atherosclerosis--particularly related to marked increases in
      obesity and diabetes in industrialized countries--a better understanding of the
      molecular mechanisms that define both atherosclerosis and aging is needed.

PMID- 20697550
TI  - Hemophilia: an amazing 35-year journey from the depths of HIV to the threshold of
      cure.
AB  - Methods developed in the early 1970s to highly purify factor VIII (FVIII) from
      the plasma of large numbers of blood donors led, for the first time, to
      concentrates of FVIII that enabled hemophiliac to self-treat, providing
      independence and opening the way to safe surgery and other treatments. But, with
      the introduction of blood-borne viruses such as HIV-1 and hepatitis C viruses
      into the blood supply, these concentrates also transmitted HIV and hepatitis to a
      high percentage of hemophiliacs. Nevertheless, from the depths of the AIDS
      epidemic in hemophilia came extraordinary scientific advances that led to
      recombinant FVIII, the identification of HIV as the agent causing AIDS, the
      eventual development of effective treatments for AIDS, gene transfer approaches
      using lentiviruses, and treatments for hepatitis C. All of these have improved
      the lives of current and future hemophiliacs and have brought us to the threshold
      of a cure.

PMID- 20697551
TI  - Resources for medical education: finding the right prescription.
AB  - What are the resources necessary to provide the highest quality education for
      medical students? This is the essential question which must be answered before a
      medical school can make a rational decision about the number of students to have
      in each class. In deciphering an objective way to determine the class size of a
      medical school, this paper explores the principles of medical education,
      accrediting organizations institutional expectations in providing a medical
      education program, and the author's personal experiences. The central tenets of a
      quality medical education include: learning by doing, student-centered learning,
      and the transmission of the attitudes, values and behaviors of the medical
      profession. This paper considers how these core components of medical education
      can be achieved and what resources are necessary to ensure that all students are
      appropriately supported.

PMID- 20697552
TI  - Colon cancer screening in the elderly: when do we stop?
AB  - Colon cancer is a major cause of cancer death in the US. Screening studies can
      prevent colon cancer and are recommended for average risk persons beginning at 50
      years of age. Compliance with these recommendations has increased, particularly
      among those over 65 years old who have an increased prevalence of cancer and for
      whom screening is covered by Medicare. However, the efficacy of screening (and
      surveillance) in this population has not been well studied. The effect of co
      morbidities and potentially increased risk of procedures performed on older
      adults are important concerns. This review addresses the benefits and harms of
      screening in the elderly. Physician emphasis on health status, life expectancy
      and patient preferences is critical in decision-making regarding colon cancer
      screening in this patient population. The recent update in the recommendations of
      the US Preventive Services Task Force (USPSTF) are reviewed.

PMID- 20697553
TI  - Holocaust denial.

PMID- 20697555
TI  - The Gordon Wilson lecture. Understanding vascular endothelium: a pilgrim's
      progress. Endothelial dysfunction, biomechanical forces and the pathobiology of
      atherosclerosis.
AB  - These are exciting times for the biomedical sciences, in general, and, in
      particular, for those who strive to understand the origins of complex human
      diseases, as we begin to focus with increasing precision on disease mechanisms at
      the cellular and molecular levels. Armed with the high-through-put technologies
      of the Post-Genomic Era, we now face the challenge of understanding biological
      systems at the level of their complex integration, and this will truly bring
      meaning to the concept of Systems Biology.

PMID- 20697556
TI  - The 2009 influenza A (H1N1) pandemic: what have we learned in the past 6 months.
AB  - The present review describes how the first influenza pandemic of the XXI century
      occurred, the characteristics of the virus that produced it, its epidemiology,
      clinical and pathological presentation, and the treatment and prevention methods
      that have been instituted. The lessons that have been learned in the first 6
      months of the pandemic include: 1) predictions were not fulfilled (it was not an
      avian virus but a swine virus that caused the pandemic, it started in the
      American continent not in Asia), 2) international cooperation was critical, 3)
      mass media played a key role communicating to the public and health care
      professionals about this evolving, and 4) preparedness plans were very important
      to confront the pandemic.

PMID- 20697557
TI  - Comparative effectiveness research: a cornerstone of healthcare reform?
AB  - Comparative Effectiveness Research (CER) has recently emerged as a major theme in
      health care reform. Unfortunately, there is a widespread lack of understanding
      about what it will do and fear that it will do more harm than good. These
      concerns include threats to individual physician's autonomy and professionalism,
      as well as fears that care will be rationed based on such findings. In this
      paper, we argue that the main components of the current healthcare reform (HCR)
      bills, which include expanding insurance while increasing efficiencies through
      cost containment, should embrace CER. This type of research will provide a
      "safeguard" against "blind" cost-containment, so that the new financial
      incentives being introduced can be actualized effectively and safely. Evidence
      for this is provided from examples from the authors' prior and current research
      as well as from the literature. We also argue that the requirement for data from
      CER will create long-term disincentives for "me-too" drugs and devices and,
      therefore, become a catalyst for effective innovation.

PMID- 20697558
TI  - The transcriptional regulator NFIL3 controls IgE production.
AB  - Cytokines are essential modulators of the immune response that underlies the
      inflammatory component of atopic asthma and other allergic diseases, lnterleukin
      4 is an important cytokine for the regulation of allergic immune responses.
      However, the molecular mechanisms that regulate the response of cells to IL-4 are
      still not completely defined. IL-4 plays an important role in B cell biology. It
      can regulate B cell differentiation. For example, IL-4 induces immunoglobulin
      heavy chain class switching to IgE by inducing germline immunoglobulin heavy
      chain transcription. It also induces expression of CD23 and MHC class II. Further
      understanding of the mechanisms by which IL-4 mediates these biologic responses
      may lead to novel mechanisms for therapeutic intervention and control of allergy.
      To define how different signaling pathways activated by IL-4 regulate gene
      transcription, we identified many differentially expressed genes by IL-4
      stimulation by microarray analysis. NFIL3 (nuclear factor, interleukin 3
      regulated) is the most strongly induced transcription factor by IL-4 stimulation
      in a STAT6-dependent manner. To analyze the role of NFIL3 in the immune system,
      we have generated NFIL3-deficient mice. NFIL3-deficient mice showed greatly
      impaired IgE production in response to antigen. NFIL3-deficient B cells fail to
      produce IgE in response to LPS plus IL-4. These defects may be due to the reduced
      production of immunoglobulin heavy chain germline epsilon transcripts in the
      absence of NFIL3. Moreover, NFIL3 KO mice sensitized and challenged with
      ovalbumin showed reduced airway hyper-responsiveness when compared to wild-type
      mice. Therefore, we hypothesize that NFIL3 is a critical regulator for IgE
      production and airway hyper-responsiveness.

PMID- 20697559
TI  - The blind leading the obese: the molecular pathophysiology of a human obesity
      syndrome.
AB  - Bardet-Biedl syndrome (BBS) is a genetically heterogeneous disorder affecting
      multiple organ systems and resulting in blindness, obesity, cognitive impairment,
      and congenital defects. Interest in the etiology of this disorder stems, in part,
      from the fact that patients with BBS develop common clinical problems, including
      obesity, diabetes and hypertension. Twelve genes independently causing BBS have
      been identified. The heterogeneity is explained by the existence of two BBS
      complexes, the BBSome consisting of seven known BBS proteins, and the BBS
      chaperone complex consisting of three known BBS proteins. The formation of the
      BBSome requires the function of the BBS chaperone complex. Both mouse and
      zebrafish data support a role for BBS genes in cilia function, and in
      intracellular and intraflagellar trafficking. From the work described here, a
      common primary function of BBS proteins has emerged, specifically the mediation
      and regulation of microtubule-based intracellular transport.

PMID- 20697560
TI  - Ku70 acetylation in neuroblastoma pathogenesis and therapy.
AB  - Neuroblastoma is a cancer that occurs in children. It develops from stem cells
      that normally give rise to parts of the peripheral nervous system and adrenal
      glands. Although most children with localized neuroblastoma are cured, children
      with wide-spread disease have a small chance of survival even after surgery,
      chemotherapy, radiation and bone marrow transplantation. Ten to fifteen percent
      of patients die from treatment complications, and long-term survival is less than
      30%. Although contemporary molecular tumor marker discoveries have improved
      prognostication, few have led to new therapeutic approaches. To solve this
      problem, we are working to understand which molecules in the stem cells from
      which this cancer arises malfunction to cause neuroblastoma and apply this
      information to develop new models to treat this disease. Our efforts have focused
      on the functional regulation of a protein called Ku70, which coordinately
      regulates DNA repair and cell death. We propose that the incorrect balance
      between these two activities underlies this cancer's development, and that re
      balancing with drug therapy offers a way to treat this disease.

PMID- 20697561
TI  - Surgery in the patient with liver disease.
AB  - Surgery is performed in patients with liver disease more frequently now than in
      the past, in part because of the long-term survival of patients with cirrhosis.
      Recent work has focused on estimating perioperative risk in patients with liver
      disease. Hemodynamic instability in the perioperative period can worsen liver
      function in patients with liver disease. Operative risk correlates with the
      severity of the underlying liver disease and the nature of the surgical
      procedure. Thorough preoperative evaluation is necessary prior to elective
      surgery. Surgery is contraindicated in patients with certain conditions, such as
      acute hepatitis, acute liver failure, and alcoholic hepatitis. Estimation of
      perioperative mortality is inexact because of the retrospective nature of and
      biased patient selection in available clinical studies. The Child-Pugh
      classification (Child-Turcotte-Pugh score) and particulary the Model for End
      Stage Liver Disease (MELD) score provide reasonable estimations of perioperative
      mortality but do not replace the need for careful preoperative preparation and
      postoperative monitoring, as early detection of complications is essential for
      improving outcomes. Medical therapy for specific manifestations of hepatic
      disease, including ascites, encephalopathy, and renal dysfunction, should be
      optimized preoperatively or, if necessary, administered in the postoperative
      period.

PMID- 20697562
TI  - Mechanisms of cell signaling by the scavenger receptor CD36: implications in
      atherosclerosis and thrombosis.
AB  - CD36 is a multifunctional membrane receptor present on mononuclear phagocytes,
      platelets, and other cells that serves as a scavenger receptor for oxidized
      phospholipids, apoptotic cells and certain microbial pathogens. On macrophages,
      CD36 interaction with oxidized LDL (oxLDL) triggers a signaling response that is
      pro-inflammatory and pro-atherogenic. The signaling pathway involves activation
      of src-family kinases, MAP kinases, and Vav family guanine nucleotide exchange
      factors and results in ligand internalization, foam cell formation and inhibition
      of migration. On platelets, CD36 interaction with oxLDL and cell-derived
      microparticles transduces intracellular signals that render them more reactive to
      low concentrations of classical agonists. In vitro studies and in vivo
      experiments in CD36 null mice have revealed an important mechanistic role for
      CD36 in atherosclerosis and thrombosis. Identification of the precise CD36
      signaling pathways in specific cells elicited in response to specific ligands may
      yield novel targets for drug development in athero-thrombotic disorders.

PMID- 20697563
TI  - The Bert and Peggy DuPont lecture. "Love, death, and commitment: twenty three
      years of HIV and genocide prevention in Africa" or "Passionate not equal
      unhinged".
AB  - Over the last 20 years, HIV emerged as the #1 cause of death in African adults,
      and the Rwanda genocide became the most concentrated mass murder in recorded
      history. Though one catastrophe surfaced slowly and inexorably while the other
      smoldered for years before exploding in 1994, the lessons learned are similar. In
      both situations, the international community has combined moral bankruptcy with a
      spectacular display of incompetence. Genocide masterminds continue living in
      Michigan, Minneapolis and Boston, brazenly planning the final extermination of
      the Tutsi. Students of law, diplomacy and international development are
      astoundingly sanguine about this, as though our current abdication of
      responsibility today is mitigated by the centuries of unprincipled idiots who
      preceded us. If medicine operated this way we'd still be treating syphilis with
      arsenic. Unfortunately, medicine has lost the moral high ground in Africa through
      missed opportunities and misappropriation of resources. In the last five years we
      have spent 20% of the US bilateral foreign assistance budget putting 2.5 million
      Africans on anti-retroviral treatment (ART), while twice that number of new HIV
      infections occurred. We tested 50 million Africans for HIV without acting on the
      evidence and common sense: rather than-transmission happens between two people.
      Had we tested Africans as couples, a prevention strategy proven to be effective
      in multiple publications since the early '90s, we could have averted more HIV
      infections than we are now treating, and at a fraction of the cost.

PMID- 20697565
TI  - The Jeremiah Metzger lecture. The origin of fibroblasts and the terminality of
      epithelial differentiation.
AB  - For 142 years the fibroblast has lived a nomadian existence among the
      interstitial spaces of the metazoan body plan. The cell surface of fibroblasts
      lacks specific identifying markers and its parental lineage has been shrouded in
      mystery. Over the last 15 years much has changed. We know now that fibroblasts
      derive from non-motile epithelial or endothelial cells through a process called
      epithelial-mesenchymal transition (EMT). In this lecture I discuss the mechanisms
      of EMT producing fibroblasts, and the inevitable conclusion that epithelia and
      endothelia, rather than being terminally differentiated, are in a state of
      nuclear diapause and ready to change phenotype in response to the demands of
      tissue repair.

PMID- 20697567
TI  - Americans on health care reform: results from polls conducted with Zogby
      International, Inc.
AB  - During a time of uncertainty regarding the future of the American health care
      system, an assessment, over time, of Americans' opinion on different legislative
      or health policy directions is a valuable asset to decision makers. After polling
      over 10,000 Americans via three polls on these topics over four months, a few
      distinct trends have emerged. When it comes to health care reform, Americans want
      a "tune-up," not a "trade-in" of their health care system by implementing reforms
      that allow the system to work more efficiently for the largest number of people
      possible, paying for it through savings found by reducing extraneous and wasteful
      spending and by increasing the quality of care. A clear sense of equity is also
      evident, as a majority do not agree with insurance companies using pre-existing
      health conditions as a metric in determining eligibility and believe in mandating
      that those who are employed, except for the smallest companies, should be
      covered.

PMID- 20697566
TI  - Unilateral renal artery stenosis causes a chronic vascular inflammatory response
      in ApoE-/- mice.
AB  - Unilateral renal artery ligation (RAL) causes a short-term vascular inflammatory
      reaction in ApoE-/- mice, but whether this persists is unknown. Partial
      constriction of the right renal artery resulted in a mild, sustained increase in
      systolic blood pressure over the 90 days of the study, whereas there was no
      change in blood pressure in mice that underwent sham-surgery. Atheroma was
      present in the abdominal aorta, with pronounced staining for macrophages (39% +/-
      9% of area of atheroma) and monocyte chemoattractant-1 (MCP-1; 40%+/-15%) in mice
      with unilateral RAL. Atheroma was also present in the carotid arteries, with
      pronounced staining for macrophages (56%+/-15%) and MCP-1 (53%+/-21%). Non-muscle
      myosin-A, a marker of smooth muscle cell dedifferentiation, was observed in
      atheroma within the abdominal aorta and carotid arteries in mice that underwent
      unilateral RAL. There were no atheroma and minimal staining for macrophages, MCP
      1 or non-muscle myosin A in carotid arteries or abdominal aorta of mice that
      underwent sham surgery. CONCLUSIONS: Chronic unilateral partial RAL results in
      the formation of atheroma in the aorta and carotid arteries of ApoE-/- mice that
      is characterized by chronic inflammation and dedifferentiation of smooth muscle
      cells.

PMID- 20697568
TI  - Tnk1/Kos1: a novel tumor suppressor.
AB  - Tnk1/Kos1 is a non-receptor protein tyrosine kinase implicated in negative
      regulation of cell growth by a mechanism involving inhibition of Ras activation
      and requiring Tnk1/Kos1's intrinsic catalytic activity. Tnk1/Kos1 null mice were
      created by homologous recombination by deleting the catalytic domain. Upon aging,
      both Tnk1+/- and Tnk1-/- mice develop spontaneous tumors, including lymphomas and
      carcinomas at high rates (i.e. 27%, and 43%, respectively), indicating that
      Tnk1/Kos1 is a tumor suppressor. Tissues from Tnk1/Kos1-null mice exhibit
      proportionally higher levels of basal and growth factor-stimulated Ras
      activation. Mechanistically, Tnk1/Kos1 requires either or both Y277 and Y287
      sites to be intact for enzymatic activity and phosphorylation of its substrate,
      growth factor receptor binding protein 2 (Grb2). Data indicate that following
      tyrosine phosphorylation of Grb2 by Tnk1/Kos1, the Grb2-Sos1 guanine exchange
      factor (GEF) complex that mediates growth factor stimulated Ras activation
      becomes disrupted, resulting in the reversal of Ras activation. Conversely, the
      loss of Tnk1/Kos1 activity results in constitutive activation of Ras due to
      prolonged stabilization/activation of the Grb2-Sos1 GEF activity. Tnk1/Kos1 is
      the first tyrosine kinase discovered to have tumor suppressor activity, and the
      mechanism of spontaneous tumor formation involves constitutive, indirect
      activation of Ras. Thus, Ras may display "oncogenic activity" without undergoing
      "oncogenic" mutation. We now find that a cohort of patients with diffuse large B
      cell lymphoma (DLBCL) display downregulation of Tnk1/Kos1 that may account for
      tumorigenesis in humans.

PMID- 20697571
TI  - Medicine's missing dimension.
AB  - In medicine we tend to restrict practice to using a purely intellectual
      understanding grounded in science to conceptualize patients and their illnesses.
      This approach is radically different from the experientially rich healing
      practices found throughout the world that presumably date to the beginning of
      humanity. Shamanistic healing is often typified as involving magical thinking and
      communication with beings other than human. These aspects of traditional healing
      are difficult to merge with science, the backbone of our medical practice.
      However, we can also describe traditional healing as meeting patients beyond the
      conventional self and beyond conceptual filters to directly face sickness and
      death in a larger context. There are a variety of traditions for learning to live
      our lives in this larger context, including contemplative religious practices and
      secular mindfulness practice. Although self discipline, effort and courage are
      likely to be required to take these paths, they can transform the practice of
      medicine into a richer experience. Using Zen Buddhism as an example of a
      contemplative spiritual approach, I will explore how it is possible to preserve a
      respectful relationship to science while engaging in healing as what the African
      Bushmen called "a life thing, a death thing".

PMID- 20697570
TI  - Theodore E. Woodward award. The evolution of obesity: insights from the mid
      Miocene.
AB  - All humans are double knockouts. Humans lack the ability to synthesize vitamin C
      due to a mutation in L-gulono-lactone oxidase that occurred during the late
      Eocene, and humans have higher serum uric acid levels due to a mutation in
      uricase that occurred in the mid Miocene. In this paper we review the hypothesis
      that these mutations have in common the induction of oxidative stress that may
      have had prosurvival effects to enhance the effects of fructose to increase fat
      stores. Fructose was the primary nutrient in fruit which was the main staple of
      early primates, but this food likely became less available during the global
      cooling that occurred at the time of these mutations. However, in today's
      society, the intake of fructose, primarily in the form of added sugars, has
      skyrocketed, while the intake of natural fruits high in vitamin C has fallen. We
      suggest that it is the interaction of these genetic changes with diet that is
      responsible for the obesity epidemic today. Hence, we propose that Neel's thrifty
      gene hypothesis is supported by these new insights into the mechanisms regulating
      fructose metabolism.

PMID- 20697573
TI  - A method for reducing pressure-induced deformation in silicone microfluidics.
AB  - Poly(dimethylsiloxane) or PDMS is an excellent material for replica molding,
      widely used in microfluidics research. Its low elastic modulus, or high
      deformability, assists its release from challenging molds, such as those with
      high feature density, high aspect ratios, and even negative sidewalls. However,
      owing to the same properties, PDMS-based microfluidic devices stretch and change
      shape when fluid is pushed or pulled through them. This paper shows how severe
      this change can be and gives a simple method for limiting this change that
      sacrifices few of the desirable characteristics of PDMS. A thin layer of PDMS
      between two rigid glass substrates is shown to drastically reduce pressure
      induced shape changes while preserving deformability during mold separation and
      gas permeability.

PMID- 20697574
TI  - E-beam lithography for micro-nanofabrication.
AB  - Electron beam lithography (EBL) is one of the tools of choice for writing micro-
      and nanostructures on a wide variety of materials. This is largely due to the
      fact that modern EBL machines are capable of writing nanometer-sized structures
      on areas up to mm(2). The aim of this contribution is to give technical and
      practical backgrounds in this extremely flexible nanofabrication technique.

PMID- 20697575
TI  - Fabrication of microfluidic devices using polydimethylsiloxane.
AB  - Polydimethylsiloxane (PDMS) is nearly ubiquitous in microfluidic devices, being
      easy to work with, economical, and transparent. A detailed protocol is provided
      here for using PDMS in the fabrication of microfluidic devices to aid those
      interested in using the material in their work, with information on the many
      potential ways the material may be used for novel devices.

PMID- 20697576
TI  - Using laser Doppler vibrometry to measure capillary surface waves on fluid-fluid
      interfaces.
AB  - Capillary wave phenomena are challenging to study, especially for microfluidics
      where the wavelengths are short, the frequencies are high, and the frequency
      distribution is rarely confined to a narrow range, let alone a single frequency.
      Those that have been studying Faraday capillary waves generated by vertical
      oscillation have chosen to work at larger scales and at low frequencies as a
      solution to this problem, trading simplicity in measurement for issues with
      gravity, boundary conditions, and the fidelity of the subharmonic capillary wave
      motion. Laser Doppler vibrometry using a Mach-Zehnder interferometer is an
      attractive alternative: The interface's motion can be characterized at
      frequencies up to 40 MHz and displacements of as little as a few tens of
      picometers.

PMID- 20697577
TI  - An integrated microfluidic system for isolation, counting, and sorting of
      hematopoietic stem cells.
AB  - This study reports an integrated microfluidic system capable of isolation,
      counting, and sorting of hematopoietic stem cells (HSCs) from cord blood in an
      automatic format by utilizing a magnetic-bead-based immunoassay. Three functional
      modules, including cell isolation, cell counting, and cell sorting modules are
      integrated on a single chip by using microfluidic technology. The cell isolation
      module is comprised of a four-membrane-type micromixer for binding of target stem
      cells and magnetic beads, two pneumatic micropumps for sample transport, and an S
      shaped channel for isolation of HSCs using a permanent magnet underneath. The
      counting and sorting of HSCs are performed by utilizing the cell counting and
      sorting modules. Experimental results show that a separation efficiency as high
      as 88% for HSCs from cord blood is achieved within 40 min for a sample volume of
      100 mul. Therefore, the development of this integrated microfluidic system may be
      promising for various applications such as stem cell research and cell therapy.

PMID- 20697578
TI  - Rapid magnetic heating treatment by highly charged maghemite nanoparticles on
      Wistar rats exocranial glioma tumors at microliter volume.
AB  - One of the most significant challenges implementing colloidal magnetic
      nanoparticles in medicine is the efficient heating of microliter quantities by
      applying a low frequency alternating magnetic field. The ultimate goal is to
      accomplish nonsurgically the treatment of millimeter size tumors. Here, we
      demonstrate the synthesis, characterization, and the in vitro as well as in vivo
      efficiency of a dextran coated maghemite (gamma-Fe(2)O(3)) ferrofluid with an
      exceptional response to magnetic heating. The difference to previous synthetic
      attempts is the high charge of the dextran coating, which according to our study
      maintains the colloidal stability and good dispersion of the ferrofluid during
      the magnetic heating stage. Specifically, in vitro 2 mul of the ferrofluid gives
      an outstanding temperature rise of 33 degrees C within 10 min, while in vivo
      treatment, by infusing 150 mul of the ferrofluid in animal model (rat) glioma
      tumors, causes an impressive cancer tissue dissolution.

PMID- 20697579
TI  - An optical counting technique with vertical hydrodynamic focusing for biological
      cells.
AB  - A BARRIER IN SCALING LABORATORY PROCESSES INTO AUTOMATED MICROFLUIDIC DEVICES HAS
      BEEN THE TRANSFER OF LABORATORY BASED ASSAYS: Where engineering meets biological
      protocol. One basic requirement is to reliably and accurately know the
      distribution and number of biological cells being dispensed. In this study, a
      novel optical counting technique to efficiently quantify the number of cells
      flowing into a microtube is presented. REH, B-lymphoid precursor leukemia, are
      stained with a fluorescent dye and frames of moving cells are recorded using a
      charge coupled device (CCD) camera. The basic principle is to calculate the total
      fluorescence intensity of the image and to divide it by the average intensity of
      a single cell. This method allows counting the number of cells with an
      uncertainty +/-5%, which compares favorably to the standard biological
      methodology, based on the manual Trypan Blue assay, which is destructive to the
      cells and presents an uncertainty in the order of 20%. The use of a microdevice
      for vertical hydrodynamic focusing, which can reduce the background noise of out
      of focus cells by concentrating the cells in a thin layer, has further improved
      the technique. Computational fluid dynamics (CFD) simulation and confocal laser
      scanning microscopy images have shown an 82% reduction in the vertical
      displacement of the cells. For the flow rates imposed during this study, a
      throughput of 100-200 cellss is achieved.

PMID- 20697580
TI  - Highly accurate deterministic lateral displacement device and its application to
      purification of fungal spores.
AB  - We have designed, built, and evaluated a microfluidic device that uses
      deterministic lateral displacement for size-based separation. The device achieves
      almost 100% purity and recovery in continuously sorting two, four, and six
      micrometer microspheres. We have applied this highly efficient device to the
      purification of fungal (Aspergillus) spores that are spherical ( approximately 4
      mum diameter) with a narrow size distribution. Such separation directly from
      culture using unfiltered A. niger suspensions is difficult due to a high level of
      debris. The device produces a two to three increase in the ratio of spores to
      debris as measured by light scatter in a flow cytometer. The procedure is
      feasible at densities up to 4.4x10(6) sporesml. This is one of the first studies
      to apply microfluidic techniques to spore separations and has demonstrated that a
      passive separation system could significantly reduce the amount of debris in a
      suspension of fungal spores with virtually no loss of spore material.

PMID- 20697581
TI  - A polymeric micro-optical interface for flow monitoring in biomicrofluidics.
AB  - We describe design and miniaturization of a polymeric optical interface for flow
      monitoring in biomicrofluidics applications based on polydimethylsiloxane
      technology, providing optical transparency and compatibility with biological
      tissues. Design and ray tracing simulation are presented as well as device
      realization and optical analysis of flow dynamics in microscopic blood vessels.
      Optics characterization of this polymeric microinterface in dynamic experimental
      conditions provides a proof of concept for the application of the device to two
      phase flow monitoring in both in vitro experiments and in vivo microcirculation
      investigations. This technology supports the study of in vitro and in vivo
      microfluidic systems. It yields simultaneous optical measurements, allowing for
      continuous monitoring of flow. This development, integrating a well-known and
      widely used optical flow monitoring systems, provides a disposable interface
      between live mammalian tissues and microfluidic devices making them accessible to
      detectionprocessing technology, in support or replacing standard intravital
      microscopy.

PMID- 20697582
TI  - An optofluidic volume refractometer using Fabry-Perot resonator with tunable
      liquid microlenses.
AB  - This letter reports the development of an optofluidic Fabry-Perot (FP) resonator,
      which consists of a microcavity and a pair of liquid microlenses. The microcavity
      forms part of the microchannel to facilitate sample injection. The liquid
      microlenses are used for efficient light coupling from the optical fiber to the
      microcavity. The liquid microlens collimates the diverging light from the optical
      fiber into the FP cavity, which provides real-time tuning to obtain the highest
      possible finesse up to 18.79. In volume refractive index measurement, a
      sensitivity of 960 nm per refractive index unit (RIU) and a detection range of
      0.043 RIU are achieved.

PMID- 20697583
TI  - Acoustic driven flow and lattice Boltzmann simulations to study cell adhesion in
      biofunctionalized mu-fluidic channels with complex geometry.
AB  - Accurately mimicking the complexity of microvascular systems calls for a
      technology which can accommodate particularly small sample volumes while
      retaining a large degree of freedom in channel geometry and keeping the price
      considerably low to allow for high throughput experiments. Here, we demonstrate
      that the use of surface acoustic wave driven microfluidics systems successfully
      allows the study of the interrelation between melanoma cell adhesion, the matrix
      protein collagen type I, the blood clotting factor von Willebrand factor (vWF),
      and microfluidic channel geometry. The versatility of the tool presented enables
      us to examine cell adhesion under flow in straight and bifurcated microfluidic
      channels in the presence of different protein coatings. We show that the addition
      of vWF tremendously increases (up to tenfold) the adhesion of melanoma cells even
      under fairly low shear flow conditions. This effect is altered in the presence of
      bifurcated channels demonstrating the importance of an elaborate hydrodynamic
      analysis to differentiate between physical and biological effects. Therefore,
      computer simulations have been performed along with the experiments to reveal the
      entire flow profile in the channel. We conclude that a combination of theory and
      experiment will lead to a consistent explanation of cell adhesion, and will
      optimize the potential of microfluidic experiments to further unravel the
      relation between blood clotting factors, cell adhesion molecules, cancer cell
      spreading, and the hydrodynamic conditions in our microcirculatory system.

PMID- 20697584
TI  - A simplified design of the staggered herringbone micromixer for practical
      applications.
AB  - We demonstrated a simple method for the device design of a staggered herringbone
      micromixer (SHM) using numerical simulation. By correlating the simulated
      concentrations with channel length, we obtained a series of concentration versus
      channel length profiles, and used mixing completion length L(m) as the only
      parameter to evaluate the performance of device structure on mixing. Fluorescence
      quenching experiments were subsequently conducted to verify the optimized SHM
      structure for a specific application. Good agreement was found between the
      optimization and the experimental data. Since L(m) is straightforward, easily
      defined and calculated parameter for characterization of mixing performance, this
      method for designing micromixers is simple and effective for practical
      applications.

PMID- 20697585
TI  - Electric charge-mediated coalescence of water droplets for biochemical
      microreactors.
AB  - This work proposes the use of charged droplets driven by the Coulombic force as
      solution-phase reaction chambers for biological microreactions. A droplet can be
      charged near an electrode under dc voltage by direct contact to the electrode.
      This process is called electrical charging of droplet (ECOD). This charged
      droplet can then be transported rapidly between electrodes following the arc of
      an electric field line by exploiting electrostatic force. As on-demand
      electrocoalescence, both alkalization of phenolphthalein and bioluminescence
      reaction of luciferase in the presence of adenosine triphosphate are studied to
      test the feasibility of the biochemical microreactors using ECOD. Two oppositely
      charged droplets are merged to have a color change immediately after
      microchemical reaction. The applicability of an ECOD-driven droplet to
      measurement of glucose concentration is also tested. The glucose concentration is
      measured using a colorimetric enzyme-kinetic method based on Trinder's reaction
      [J. Clin. Pathol. 22, 158 (1969)]. The color change in the merged droplet is
      detected with an absorbance measurement system consisting of a photodiode and a
      light emitting diode.

PMID- 20697586
TI  - Amplification of SPPS150 and Salmonella typhi DNA with a high throughput
      oscillating flow polymerase chain reaction device.
AB  - In this paper, a novel oscillating flow polymerase chain reaction (PCR) device
      was designed and fabricated to amplify SPPS150 and salmonella typhi. In this new
      design, the samples are shuttled (oscillating flow) inside a microfluidic chip to
      three different temperature zones required for DNA amplification. The
      amplification cycle time has markedly been reduced as the reagent volume used was
      only about 25% of that used in conventional PCRs. Bubble formation and adsorption
      issues commonly associated to chip based PCR were also eliminated. Based on the
      performance evaluated, it is demonstrated that this oscillating flow PCR has the
      advantages of both the stationary chamber and continuous flow PCR devices.

PMID- 20697587
TI  - Fast and reliable droplet transport on single-plate electrowetting on dielectrics
      using nonfloating switching method.
AB  - In a droplet transport based on electrowetting on dielectrics, the parallel-plate
      configuration is more popular than the single-plate one because the droplet
      transport becomes increasingly difficult without cover plate. In spite of the
      improved transport performance, the parallel-plate configuration often limits the
      access to the peripheral components, requesting the removal of the cover plate,
      the single-plate configuration. We investigated the fundamental features of
      droplet transport for the single-plate configuration. We compared the performance
      of several switching methods with respect to maximum speed of successive
      transport without failure and suggested nonfloating switching method which is
      inherently free from the charge-residue problem and exerts greater force on a
      droplet than conventional switching methods. A simple theory is provided to
      understand the different results for the switching methods.

PMID- 20697588
TI  - A prototypic microfluidic platform generating stepwise concentration gradients
      for real-time study of cell apoptosis.
AB  - This work describes the development of a prototypic microfluidic platform for the
      generation of stepwise concentration gradients of drugs. A sensitive apoptotic
      analysis method is integrated into this microfluidic system for studying
      apoptosis of HeLa cells under the influence of anticancer drug, etoposide, with
      various concentrations in parallel; it measures the yellow fluorescent
      proteincyan fluorescent protein fluorescence resonance energy transfer (FRET)
      signal that responds to the activation of caspase-3, an indicator of cell
      apoptosis. Sets of microfluidic valves on the chip generate stepwise
      concentration gradient of etoposide in various cell-culture microchambers. The
      FRET signals from multiple chambers are simultaneously monitored under a
      fluorescent microscope for long-time observation and the on-chip results are
      compared with those from 96-well plate study and the methylthiazolyldiphenyl
      tetrazolium bromide (MTT) assay. The microfluidic platform shows several
      advantages including high-throughput capacity, low drug consumption, and high
      sensitivity.

PMID- 20697590
TI  - Construction by dielectrophoresis of microbial aggregates for the study of
      bacterial cell dormancy.
AB  - A study of the effect of aggregate size on the resuscitation of dormant M.
      smegmatis was conducted by constructing cell aggregates with defined sizes and
      shapes using dielectrophoresis and monitoring the resuscitation process under
      controlled laboratorial conditions in a long-term cell feeding system.
      Differently sized cell aggregates were created on the surface of indium tin oxide
      coated microelectrodes, their heights and shapes controlled by the strength of
      the induced electric field and the shape of the microelectrodes. Both two
      dimensional (ring-patterned) and three-dimensional cell aggregates were produced.
      The cell aggregates were maintained under sterile conditions at 37 degrees C for
      up to 14 days by continuously flushing Sauton's medium through the chamber.
      Resuscitation of dormant M. smegmatis was evaluated by the production of the
      fluorescent dye 5-cyano-2,3-ditolyltetrazolium chloride. The results confirm that
      the resuscitation of dormant M. smegmatis is triggered by the accumulation of a
      resuscitation promoting factor inside the aggregates by diffusion limitation.

PMID- 20697589
TI  - Review article-dielectrophoresis: status of the theory, technology, and
      applications.
AB  - A review is presented of the present status of the theory, the developed
      technology and the current applications of dielectrophoresis (DEP). Over the past
      10 years around 2000 publications have addressed these three aspects, and current
      trends suggest that the theory and technology have matured sufficiently for most
      effort to now be directed towards applying DEP to unmet needs in such areas as
      biosensors, cell therapeutics, drug discovery, medical diagnostics,
      microfluidics, nanoassembly, and particle filtration. The dipole approximation to
      describe the DEP force acting on a particle subjected to a nonuniform electric
      field has evolved to include multipole contributions, the perturbing effects
      arising from interactions with other cells and boundary surfaces, and the
      influence of electrical double-layer polarizations that must be considered for
      nanoparticles. Theoretical modelling of the electric field gradients generated by
      different electrode designs has also reached an advanced state. Advances in the
      technology include the development of sophisticated electrode designs, along with
      the introduction of new materials (e.g., silicone polymers, dry film resist) and
      methods for fabricating the electrodes and microfluidics of DEP devices (photo
      and electron beam lithography, laser ablation, thin film techniques, CMOS
      technology). Around three-quarters of the 300 or so scientific publications now
      being published each year on DEP are directed towards practical applications, and
      this is matched with an increasing number of patent applications. A summary of
      the US patents granted since January 2005 is given, along with an outline of the
      small number of perceived industrial applications (e.g., mineral separation,
      micropolishing, manipulation and dispensing of fluid droplets, manipulation and
      assembly of micro components). The technology has also advanced sufficiently for
      DEP to be used as a tool to manipulate nanoparticles (e.g., carbon nanotubes,
      nano wires, gold and metal oxide nanoparticles) for the fabrication of devices
      and sensors. Most efforts are now being directed towards biomedical applications,
      such as the spatial manipulation and selective separationenrichment of target
      cells or bacteria, high-throughput molecular screening, biosensors, immunoassays,
      and the artificial engineering of three-dimensional cell constructs. DEP is able
      to manipulate and sort cells without the need for biochemical labels or other
      bioengineered tags, and without contact to any surfaces. This opens up
      potentially important applications of DEP as a tool to address an unmet need in
      stem cell research and therapy.

PMID- 20697591
TI  - Separation by dielectrophoresis of dormant and nondormant bacterial cells of
      Mycobacterium smegmatis.
AB  - The dielectrophoretic behavior of active, dead, and dormant Mycobacterium
      smegmatis bacterial cells was studied. It was found that the 72-h-old dormant
      cells had a much higher effective particle conductivity (812+/-10 muS cm(-1)),
      almost double that of active cells (560+/-20 muS cm(-1)), while that of dead
      (autoclaved) M. smegmatis cells was the highest (950+/-15 muS cm(-1)) overall. It
      was also found that at 80 kHz, 900 muS cm(-1) dead cells were attracted at the
      edges of interdigitated castellated electrodes by positive dielectrophoresis, but
      dormant cells were not. Similarly, at 120 kHz, 2 muS cm(-1) active cells were
      attracted and dormant cells were not. Using these findings a dielectrophoresis
      based microfluidic separation system was developed in which dead and active cells
      were collected from a given cell suspension, while dormant cells were eluted.

PMID- 20697592
TI  - Dielectrophoretic cell trapping and parallel one-to-one fusion based on field
      constriction created by a micro-orifice array.
AB  - Micro-orifice based cell fusion assures high-yield fusion without compromising
      the cell viability. This paper examines feasibility of a dielectrophoresis (DEP)
      assisted cell trapping method for parallel fusion with a micro-orifice array. The
      goal is to create viable fusants for studying postfusion cell behavior. We
      fabricated a microfluidic chip that contained a chamber and partition. The
      partition divided the chamber into two compartments and it had a number of
      embedded micro-orifices. The voltage applied to the electrodes located at each
      compartment generated an electric field distribution concentrating in micro
      orifices. Cells introduced into each compartment moved toward the micro-orifice
      array by manipulation of hydrostatic pressure. DEP assisted trapping was used to
      keep the cells in micro-orifice and to establish cell to cell contact through
      orifice. By applying a pulse, cell fusion was initiated to form a neck between
      cells. The neck passing through the orifice resulted in immobilization of the
      fused cell pair at micro-orifice. After washing away the unfused cells, the chip
      was loaded to a microscope with stage top incubator for time lapse imaging of the
      selected fusants. The viable fusants were successfully generated by fusion of
      mouse fibroblast cells (L929). Time lapse observation of the fusants showed that
      fused cell pairs escaping from micro-orifice became one tetraploid cell. The
      generated tetraploid cells divided into three daughter cells. The fusants
      generated with a smaller micro-orifice (diameter approximately 2 mum) were kept
      immobilized at micro-orifice until cell division phase. After observation of two
      synchronized cell divisions, the fusant divided into four daughter cells. We
      conclude that the presented method of cell pairing and fusion is suitable for
      high-yield generation of viable fusants and furthermore, subsequent study of
      postfusion phenomena.

PMID- 20697593
TI  - A miniaturized continuous dielectrophoretic cell sorter and its applications.
AB  - There is great interest in highly sensitive separation methods capable of quickly
      isolating a particular cell type within a single manipulation step prior to their
      analysis. We present a cell sorting device based on the opposition of
      dielectrophoretic forces that discriminates between cell types according to their
      dielectric properties, such as the membrane permittivity and the cytoplasm
      conductivity. The forces are generated by an array of electrodes located in both
      sidewalls of a main flow channel. Cells with different dielectric responses
      perceive different force magnitudes and are, therefore, continuously focused to
      different equilibrium positions in the flow channel, thus avoiding the need of a
      specific cell labeling as discriminating factor. We relate the cells' dielectric
      response to their output position in the downstream channel. Using this
      microfluidic platform that integrates a method of continuous-flow cell separation
      based on multiple frequency dielectrophoresis, we succeeded in sorting viable
      from nonviable yeast with nearly 100% purity. The method also allowed to increase
      the infection rate of a cell culture up to 50% of parasitemia percentage, which
      facilitates the study of the parasite cycle. Finally, we prove the versatility of
      our device by synchronizing a yeast cell culture at a particular phase of the
      cell cycle avoiding the use of metabolic agents interfering with the cells'
      physiology.

PMID- 20697594
TI  - Trapping single human osteoblast-like cells from a heterogeneous population using
      a dielectrophoretic microfluidic device.
AB  - We describe a system for the isolation, concentration, separation, and recovery
      of human osteoblast-like cells from a heterogeneous population using
      dielectrophoretic ring traps. Cells flowing in a microfluidic channel are
      immobilized inside an electric field cage using negative dielectrophoresis. A
      planar ring electrode creates a closed trap while repelling surrounding cells.
      Target cells are identified by fluorescent labeling, and are trapped as they pass
      across a ring electrode by an automated system. We demonstrate recovery of small
      populations of human osteoblast-like cells with a purity of 100%, which in turn
      demonstrates the potential of such a device for cell selection from a
      heterogeneous population.

PMID- 20697595
TI  - Liquid dielectrophoresis and surface microfluidics.
AB  - Liquid dielectrophoresis (L-DEP), when deployed at microscopic scales on top of
      hydrophobic surfaces, offers novel ways of rapid and automated manipulation of
      very small amounts of polar aqueous samples for microfluidic applications and
      development of laboratory-on-a-chip devices. In this article we highlight some of
      the more recent developments and applications of L-DEP in handling and processing
      of various types of aqueous samples and reagents of biological relevance
      including emulsions using such microchip based surface microfluidic (SMF)
      devices. We highlighted the utility of these devices for on-chip bioassays
      including nucleic acid analysis. Furthermore, the parallel sample processing
      capabilities of these SMF devices together with suitable on- or off-chip
      detection capabilities suggest numerous applications and utility in conducting
      automated multiplexed assays, a capability much sought after in the high
      throughput diagnostic and screening assays.

PMID- 20697596
TI  - Fabrication and characterization of nanomaterial-based sensors using
      dielectrophoresis.
AB  - Dielectrophoresis (DEP) is an electrokinetic motion of dielectrically polarized
      materials in nonuniform electric fields. DEP has been successfully applied to
      manipulation of nanomaterials including carbon nanotubes (CNTs), metallic
      nanoparticles, and semiconducting nanowires. Under positive DEP force, which
      attracts nanomaterials toward the higher field region, nanomaterials are trapped
      in the electrode gap and automatically establish good electrical connections
      between them and the external measuring circuit. This feature allows us a fast,
      simple, and low-cost fabrication of nanomaterial-based sensors based on a bottom
      up approach. This paper first presents a theoretical background of DEP phenomena
      and then reviews recent works of the present author, which were aimed to develop
      nanomaterial-based sensors, such as a CNT gas sensor and a ZnO nanowire
      photosensor, using DEP fabrication technique. It is also demonstrated that DEP
      technique enables self-formation of interfaces between various nanomaterials,
      which can be also applicable as novel sensing transducers.

PMID- 20697597
TI  - Dielectrophoresis of DNA: Quantification by impedance measurements.
AB  - Dielectrophoretic properties of DNA have been determined by measuring capacitance
      changes between planar microelectrodes. DNA sizes ranged from 100 bp to 48 kbp,
      DNA concentrations from below 0.1 to 70 mugml. Dielectrophoretic spectra
      exhibited maximum response around 3 kHz and 3 MHz. The strongest response was
      found for very long DNA (above 10 kbp) and for short 100 bp fragments, which
      corresponds to the persistence length of DNA. The method allows for an
      uncomplicated, automatic acquisition of the dielectrophoretic properties of
      submicroscopical objects without the need for labeling protocols or optical
      accessibility.

PMID- 20697598
TI  - Interaction between cells in dielectrophoresis and electrorotation experiments.
AB  - Progress in microelectrode-based technologies has facilitated the development of
      sophisticated methods for manipulating and separating cells, bacteria, and other
      bioparticles. For many of these various applications, the theoretical modeling of
      the electrical response of compartmentalized particles to an external field is
      important. In this paper we address the analysis of the interaction between cells
      immersed in rf fields. We use an integral formulation of the problem derived from
      a consideration of the charge densities induced at the interfaces of the particle
      compartments. The numerical solution by a boundary element technique allows
      characterization of their dielectric properties. Experimental validation of this
      theoretical model is obtained by investigating two effects: (1) The influence
      that dipolar "pearl chaining" has on the dielectrophoretic behavior of human T
      lymphocytes and (2) the frequency variation of the spin and orbital torques of
      approaching insulinoma beta-cells in a rotating field.

PMID- 20697599
TI  - Dynamic double layer effects on ac-induced dipoles of dielectric nanocolloids.
AB  - Normal and tangential surface ionic currents around low-permittivity nanocolloids
      with surface charges are shown to produce three different conductive mechanisms
      for ac-induced dipoles, all involving dynamic space charge accumulation at the
      double layerbulk interface with a conductivity jump. However, the distinct
      capacitor dimensions and diffusive contributions produce three disparate
      crossover frequencies at which the induced dipole reverses direction relative to
      the bulk field. A highly conducting collapsed diffuse layer, with bulk ion
      mobility, renders the particle conductive and produces an ionic strength
      independent crossover frequency for weak electrolytes. A precipitous drop in
      crossover frequency occurs at high ionic strengths when charging occurs only at
      the poles through field focusing around the insulated colloid. A peculiar maximum
      in crossover frequency exists between these two asymptotes for colloids smaller
      than a critical size when normal charging of the diffuse layer occurs over the
      entire surface. The crossover frequency data for latex nanocolloids of various
      sizes in different electrolytes of wide ranging ionic strengths are collapsed by
      explicit theoretical predictions without empirical parameters.

PMID- 20697600
TI  - Dielectrophoretic separation of mouse melanoma clones.
AB  - Dielectrophoresis (DEP) is employed to differentiate clones of mouse melanoma
      B16F10 cells. Five clones were tested on microelectrodes. At a specific
      excitation frequency, clone 1 showed a different DEP response than the other
      four. Growth rate, melanin content, recovery from cryopreservation, and in vitro
      invasive studies were performed. Clone 1 is shown to have significantly different
      melanin content and recovery rate from cryopreservation. This paper reports the
      ability of DEP to differentiate between two malignant cells of the same origin.
      Different DEP responses of the two clones could be linked to their melanin
      content.

PMID- 20697601
TI  - Harnessing RNA interference for the treatment of viral infections.
AB  - Exploiting the RNA interference (RNAi) pathway to inhibit viral gene expression
      has become an active field of research. The approach has potential for
      therapeutic application and several viruses are susceptible to RNAi-mediated
      knockdown. Differences in the characteristics of individual viruses require that
      viral gene silencing be tailored to specific infections. Important considerations
      are viral tissue tropism, acute or chronic nature of the infection and the
      efficiency with which antiviral sequences can be delivered to affected tissue.
      Both synthetic short interfering RNAs (siRNAs) and expressed RNAi activators are
      being developed for viral therapy. The sustained silencing of expressed antiviral
      sequences is useful for countering chronic viral infection. siRNAs, which may be
      chemically modified to improve specificity and stability, are being developed for
      knockdown of viruses that cause acute or chronic infections. Preventing viral
      escape from silencing is important and overcoming this problem using
      combinatorial RNAi or through silencing of host dependency factors is promising.
      Although improving delivery efficiency and limiting off-target effects remain
      obstacles, rapid progress continues to be made in the field and it is likely that
      the goal of achieving licensed RNAi-based viral therapies will soon be realized.

PMID- 20697602
TI  - The role of GABA(A) receptor subtypes as analgesic targets.
AB  - Recent GABA(A) receptor drug discovery efforts have culminated in the development
      of transgenic mice and subtype-selective pharmacological tools, enhancing our
      understanding of the major inhibitory neural system in the central nervous
      system. Notably, subtype-selective tools have demonstrated in both preclinical
      studies and, to some extent, in man that it is possible to develop drugs that
      share the clinical benefits of benzodiazepines (e.g., anxiolysis) while obviating
      some adverse effects of these clinically important drugs. Here, we highlight
      chronic pain as another therapeutic area in which subtype-selective GABA(A)
      receptor drugs might have clinical utility. Specifically, based on research in
      animal models of inflammatory/neuropathic pain, we suggest that subtype-selective
      positive modulators of GABA(A) alpha(2/3) receptors might reverse a loss of
      postsynaptic GABA(A) receptor-mediated inhibitory function in spinal cord,
      leading to analgesia. However, alteration of presynaptic inhibitory neural
      transmission in chronic pain suggests that drugs that negatively modulate GABA(A)
      receptors might also be effective analgesics. For example, the non-selective
      negative allosteric modulator FG-7142 reverses allodynia in an animal model of
      neuropathic pain. Importantly, these two mechanisms are not mutually exclusive.
      Further clinical exploration in pain of available positive and negative subtype
      selective modulators that have been administered to humans would considerably aid
      back translation, allowing for improved therapeutic development.

PMID- 20697603
TI  - Nerve growth factor eye drops to treat glaucoma.
AB  - Since the discovery of nerve growth factor (NGF) in the 1950s, scientists have
      had great expectations for NGF in the treatment of neurodegenerative diseases.
      The main obstacle to overcome was the blood-brain barrier, which NGF does not
      cross when administered systemically. Our research group has recently
      demonstrated that topically instilled NGF eye drops are effective in treating
      several ocular diseases such as neurotrophic and autoimmune corneal ulcers.
      Pharmacodynamic studies have also shown that NGF eye drops have the ability to
      target the optic nerve and brain, thus finally opening-up avenues of research in
      pursuit of a novel drug for neurodegenerative diseases. In this review, clinical
      trials of systemically and topically administered NGF are discussed, as well as
      recent progress in the production of biologically active recombinant human NGF
      and innovative delivery routes. The pharmacological activity of NGF eye drops in
      ocular surface, retina and optic nerve diseases are also discussed.

PMID- 20697604
TI  - Adenoviral gene therapy in high-grade malignant glioma.
AB  - Despite advances in surgical techniques, improvement in radiation treatments and
      chemotherapy, and the addition of new biological agents to the armamentarium, the
      median survival of patients with high-grade malignant glioma has changed little
      over recent decades. However, advances in the fundamental understanding of brain
      tumor biology suggest that targeting molecular pathways underlying carcinogenesis
      may provide alternative or additional approaches to glioma treatment. Viruses,
      particularly adenoviruses, have been critical in the application and development
      of these molecular approaches. Adenoviruses have been engineered to function as
      vectors for delivering therapeutic genes for gene therapy, and as direct
      cytotoxic agents for oncolytic viral therapy. The purpose of this review is to
      provide a prospective on the use of adenoviruses in high-grade malignant glioma
      therapy.

PMID- 20697605
TI  - ADAM metallopeptidase domain 33 (ADAM33): identification and role in airways
      disease.
AB  - Asthma is a common disorder of the airways which exhibit variable obstruction
      associated with hyperresponsiveness linked to altered smooth muscle. Although
      environmental factors are important in the origins and progression of asthma, it
      is a disorder with high heritability. The identification of ADAM33 (ADAM
      metallopeptidase domain 33, a disintegrin and metalloproteinase domain 33) as the
      first novel asthma gene has implications for the mechanisms of airway hyper
      responsiveness and airway wall remodeling. This review discusses the molecular
      regulation of ADAM33, its link to asthma and chronic obstructive pulmonary
      disease and newly identified functions. These all point to ADAM33 being a key
      molecule in the development and progression of asthma by contributing to smooth
      muscle and vascular modeling and remodeling.

PMID- 20697606
TI  - Molecule of the month. NGR-hTNF.

PMID- 20697607
TI  - The kinetic isotope effect in the search for deuterated drugs.
AB  - The kinetic isotope effect has long been exploited by physical organic chemists
      to study reaction mechanisms due to its effect on reaction rates when cleavage of
      a C-isotope bond is rate determining. Medicinal chemists have also used the
      deuterium kinetic isotope effect to slow the cytochrome P450 metabolism of the
      deuterated versions of drug candidates, with the first in vitro microsome studies
      of deuterated morphine appearing in the literature in the 1960s, and a deuterated
      alanine compound from Merck going all the way to phase IIb in the 1970s. The
      recent emergence of companies such as Concert Pharmaceuticals and Auspex
      Pharmaceuticals, based solely on the idea of deuterium-for-hydrogen versions of
      existing drugs, has reinvigorated the backers of the deuterium camp, and
      established the strategy as a viable low-risk approach to drug development. A
      history of the deuterium kinetic isotope effect is presented, along with examples
      of deuterated drugs that span 50 years, from 1960 to present day. Specific
      examples of compounds from the Concert and Auspex pipelines are also analyzed and
      the pros and cons of their approach are discussed.

PMID- 20697608
TI  - Studies on highly regio- and stereoselective hydration of 1,2-allenylic
      sulfoxides.
AB  - A highly regio- and stereoselective hydration of 1,2-allenylic sulfoxides in
      which proton served as the electrophile was reported. Through the X-ray
      diffraction study, it was concluded that the reaction may proceed via a 5
      membered cyclic intermediate following by attack of the (-)OH at the sulfur atom.

PMID- 20697609
TI  - Computer simulation of reactions in beta-cyclodextrin molecular reactors:
      transition state recognition.
AB  - Cyclodextrins have attracted much interest in recent years because of their
      potential use as molecular reactors allowing organic reactions in aqueous
      solution. To better understand their effect on reaction mechanisms, we have
      carried out a computational study of a prototypical process (neutral ester
      hydrolysis) in a beta-cyclodextrin (beta-CD). Two models have been used for the
      reactor. The first and simpler one assumes that the medium can be described by a
      polarizable dielectric continuum. The second one takes into account the discrete
      nature of the beta-CD and water molecules thanks to a computational approach that
      combines the use of Quantum Mechanics, Molecular Mechanics and Molecular Dynamics
      techniques. We focus on neutral pH processes for which either acceleration or
      inhibition has experimentally been observed depending on ester derivatives. Our
      calculations rationalize such observations by showing that the two reaction
      mechanisms usually invoked for hydrolysis, stepwise (involving two transitions
      states with formation of a -C(OH)(2)OR tetrahedral intermediate) and concerted,
      undergo opposite effects in the beta-CD environment. The results highlight the
      role played by molecular shape recognition. Thus, in spite of a higher polarity
      exhibited by the three transition states with respect to the reactants, the
      interactions with the beta-CD cavity may either increase or decrease the
      activation barrier due to different 3D-arrangements of the chemical structures.

PMID- 20697610
TI  - Luminescent platinum complexes containing phosphorus-linked silole ligands.
AB  - A series of Pt(ii) complexes containing silole-based ligands with
      diphenylphosphino groups terminally bound to a conjugated organic linker unit
      coordinated to the silole ring in the 2- or 2,5-positions, 1,1-dimethyl-2-(5'
      diphenylphosphino-2'-thienyl)-3,4-diphenylsilole (4), 1,1-dimethyl-2,5-bis(5'
      diphenylphosphino-2'-thienyl)-3,4-diphenylsilole (5), and 1,1-dimethyl-2,5-bis(4'
      diphenylphosphinophenyl)-3,4-diphenylsilole (8), have been prepared from
      (cod)PtX(2) (X = Cl, Me, C(2)Ph) precursors. Mononuclear, cis-P(2)PtX(2) (P = 4)
      complexes 6-7 were produced from silole 4 whereas dinuclear macrocyclic, cis-cis
      X(2)Pt(P-P)(2)PtX(2) (P-P = 5 or 8) complexes 9-13 were produced from siloles 5
      and 8. The solid state structure of the dinuclear complex 13 obtained from
      reaction of (cod)Pt(C(2)Ph)(2) with silole 8, was confirmed by X-ray
      crystallography. The optical properties of the siloles and the platinum complexes
      were studied by UV-vis and fluorescence spectroscopy in solution and were found
      to exhibit long wavelength absorption and emission bands attributed to the pi-pi*
      transitions of the silole core.

PMID- 20697611
TI  - Graphene nanoribbon band-gap expansion: broken-bond-induced edge strain and
      quantum entrapment.
AB  - An edge-modified tight-binding (TB) approximation has been developed, enabling us
      to clarify the energetic origin of the width-dependent band gap (E(G)) expansion
      of the armchaired and the reconstructed zigzag-edged graphene nanoribbons with
      and without hydrogen termination. Consistency between the TB and the density
      function theory calculations affirmed that: (i) the E(G) expansion originates
      from the Hamiltonian perturbation due to the shorter and stronger bonds between
      undercoordinated atoms, (ii) the combination of the edge-to-width ratio with a
      local bond strain up to 30% and the associated 152% potential well depression
      determines the width dependent E(G) change; and, (iii) hydrogen termination
      affects insignificantly the band gap width as the H-passivation minimizes the
      midgap impurity states.

PMID- 20697612
TI  - Adsorbed Tween 80 is unique in its ability to improve the stability of gold
      nanoparticles in solutions of biomolecules.
AB  - This report shows that, of the Tween series (Tween 20, Tween 40, Tween 60 and
      Tween 80) of nonionic surfactants adsorbed on gold nanoparticles (NPs), Tween 80
      makes the NPs most stably dispersed in aqueous solutions with or without the
      presence of representative biological molecules, such as nucleic acids or
      proteins of different sizes, isoelectric points (pIs) and shapes. In addition,
      the stability of gold NPs already modified with poly(L-lysine)-graft
      poly(ethylene glycol) (PLL-PEG) or hexa(ethylene glycol)-terminated
      undecanylthiol (HS(CH(2))(11)EG(6)OH) is further improved in solutions of
      proteins when Tween 80 is co-adsorbed on the gold NPs. This strategy is the most
      effective when adsorption of Tween 80 on gold NPs precedes the coating of PLL-PEG
      or HS(CH(2))(11)EG(6)OH on the NPs.

PMID- 20697613
TI  - Additive nanoscale embedding of functional nanoparticles on silicon surface.
AB  - We present a novel additive process, which allows the spatially controlled
      integration of nanoparticles (NPs) inside silicon surfaces. The NPs are placed
      between a conductive stamp and a silicon surface; by applying a bias voltage a
      SiO(2) layer grows underneath the stamp protrusions, thus embedding the
      particles. We report the successful nanoembedding of CoFe(2)O(4) nanoparticles
      patterned in lines, grids and logic structures.

PMID- 20697614
TI  - Water formation at low temperatures by surface O2 hydrogenation I:
      Characterization of ice penetration.
AB  - Water is the main component of interstellar ice mantles, is abundant in the solar
      system and is a crucial ingredient for life. The formation of this molecule in
      the interstellar medium cannot be explained by gas-phase chemistry only and its
      surface hydrogenation formation routes at low temperatures (O, O(2), O(3)
      channels) are still unclear and most likely incomplete. In a previous paper we
      discussed an unexpected zeroth-order H(2)O production behavior in O(2) ice
      hydrogenation experiments compared to the first-order H(2)CO and CH(3)OH
      production behavior found in former studies on hydrogenation of CO ice. In this
      paper we experimentally investigate in detail how the structure of O(2) ice leads
      to this rare behavior in reaction order and production yield. In our experiments
      H atoms are added to a thick O(2) ice under fully controlled conditions, while
      the changes are followed by means of reflection absorption infrared spectroscopy
      (RAIRS). The H-atom penetration mechanism is systematically studied by varying
      the temperature, thickness and structure of the O(2) ice. We conclude that the
      competition between reaction and diffusion of the H atoms into the O(2) ice
      explains the unexpected H(2)O and H(2)O(2) formation behavior. In addition, we
      show that the proposed O(2) hydrogenation scheme is incomplete, suggesting that
      additional surface reactions should be considered. Indeed, the detection of newly
      formed O(3) in the ice upon H-atom exposure proves that the O(2) channel is not
      an isolated route. Furthermore, the addition of H(2) molecules is found not to
      have a measurable effect on the O(2) reaction channel.

PMID- 20697615
TI  - Water formation at low temperatures by surface O2 hydrogenation II: The reaction
      network.
AB  - Water is abundantly present in the Universe. It is the main component of
      interstellar ice mantles and a key ingredient for life. Water in space is mainly
      formed through surface reactions. Three formation routes have been proposed in
      the past: hydrogenation of surface O, O(2), and O(3). In a previous paper
      [Ioppolo et al., Astrophys. J., 2008, 686, 1474] we discussed an unexpected non
      standard zeroth-order H(2)O(2) production behaviour in O(2) hydrogenation
      experiments, which suggests that the proposed reaction network is not complete,
      and that the reaction channels are probably more interconnected than previously
      thought. In this paper we aim to derive the full reaction scheme for O(2) surface
      hydrogenation and to constrain the rates of the individual reactions. This is
      achieved through simultaneous H-atom and O(2) deposition under ultra-high vacuum
      conditions for astronomically relevant temperatures. Different H/O(2) ratios are
      used to trace different stages in the hydrogenation network. The chemical changes
      in the forming ice are followed by means of reflection absorption infrared
      spectroscopy (RAIRS). New reaction paths are revealed as compared to previous
      experiments. Several reaction steps prove to be much more efficient (H + O(2)) or
      less efficient (H + OH and H(2) + OH) than originally thought. These are the main
      conclusions of this work and the extended network concluded here will have
      profound implications for models that describe the formation of water in space.

PMID- 20697616
TI  - Unveiling the mechanism of uptake and sub-cellular distribution of cerium oxide
      nanoparticles.
AB  - Cerium oxide nanoparticles (CNPs) have been recently studied for their potent
      superoxide scavenging properties in both cell and animal model systems. Data from
      these model systems have shown that exposure of cells to CNPs results in the
      protection against reactive oxygen species (ROS). Despite these exciting
      findings, very little is known regarding the uptake or subcellular distribution
      of these nanomaterials inside cells. In this study we utilized fluorophore
      (carboxyfluorescein) conjugated cerium oxide NPs (CCNPs) to study the mechanism
      of uptake and to elucidate the subcellular localization of CNPs using a
      keratinocyte model system. We observed rapid uptake (within 3 h) of CCNPs that
      was governed by energy-dependent, clathrin-mediated and caveolae-mediated
      endocytic pathways. We found CCNPs co-localized with mitochondria, lysosomes and
      endoplasmic reticulum as well as being abundant in the cytoplasm and the nucleus.
      Given the radical scavenging properties of cerium oxide and the widespread
      cellular disposition we observed, CNPs likely act as cellular antioxidants in
      multiple compartments of the cell imparting protection against a variety of
      oxidant injuries.

PMID- 20697617
TI  - SpaciMS: spatial and temporal operando resolution of reactions within catalytic
      monoliths.
AB  - Monolithic catalysts are widely used as structured catalysts, especially in the
      abatement of pollutants. Probing what happens inside these monoliths during
      operation is, therefore, vital for modelling and prediction of the catalyst
      behavior. SpaciMS is a spatially resolved capillary-inlet mass spectroscopy
      system allowing for the generation of spatially resolved maps of the reactions
      within monoliths. In this study SpaciMS results combined with 3D CFD modelling
      demonstrate that SpaciMS is a highly sensitive and minimally invasive technique
      that can provide reaction maps as well as catalytic temporal behavior. Herein we
      illustrate this by examining kinetic oscillations during a CO oxidation reaction
      over a Pt/Rh on alumina catalyst supported on a cordierite monolith. These
      oscillations were only observed within the monolith by SpaciMS between 30 and 90%
      CO conversion. Equivalent experiments performed in a plug-flow reactor using this
      catalyst in a crushed form over a similar range of reaction conditions did not
      display any oscillations demonstrating the importance of intra monolith analysis.
      This work demonstrates that the SpaciMS offers an accurate and comprehensive
      picture of structured catalysts under operation.

PMID- 20697618
TI  - Effect of hydrophobic interaction cooperating with double Lewis acid activation
      in a zinc(II) phosphodiesterase mimic.
AB  - The novel dinuclear Zn(ii) complex (1) containing a beta-CD dimer could
      accelerate BNPP (a DNA substitute) hydrolysis more efficiently than catalyze HPNP
      (a RNA substitute) transesterification with different mechanisms involved; the
      beta-CDs played remarkably different roles.

PMID- 20697619
TI  - Novel high-performance nanohybrid polyelectrolyte membranes based on bio
      functionalized montmorillonite for fuel cell applications.
AB  - This study is concerned with electrochemical investigation of novel high
      performance proton exchange membranes based on bio-functionalized montmorillonite
      and Nafion. It was found that the incorporation of 2 wt% BMMT into Nafion
      polyelectrolyte matrix results in significantly improved methanol-air fuel cell
      efficiency of 30% compared to 14% for Nafion(R)117, and about 23-times higher
      membrane selectivity.

PMID- 20697620
TI  - Fine tuning Exo2, a small molecule inhibitor of secretion and retrograde
      trafficking pathways in mammalian cells.
AB  - The small molecule 4-hydroxy-3-methoxybenzaldehyde (5,6,7,8
      tetrahydro[1]benzothieno[2,3-d]pyrimidin-4-yl)hydrazone (Exo2) stimulates
      morphological changes at the mammalian Golgi and trans-Golgi network that are
      virtually indistinguishable from those induced by brefeldin A. Both brefeldin A
      and Exo2 protect cells from intoxication by Shiga(-like) toxins by acting on
      other targets that operate at the early endosome, but do so at the cost of high
      toxicity to target cells. The advantage of Exo2 is that it is much more amenable
      to chemical modification and here we report a range of Exo2 analogues produced by
      modifying the tetrahydrobenzothienopyrimidine core, the vanillin moiety and the
      hydrazone bond that links these two. These compounds were examined for the
      morphological changes they stimulated at the Golgi stack, the trans-Golgi network
      and the transferrin receptor-positive early endosomes and this activity
      correlated with their inherent toxicity towards the protein manufacturing ability
      of the cell and their protective effect against toxin challenge. We have
      developed derivatives that can separate organelle morphology, target specificity,
      innate toxicity and toxin protection. Our results provide unique compounds with
      low toxicity and enhanced specificity to unpick the complexity of membrane
      trafficking networks.

PMID- 20697621
TI  - Rapid formation of all-trans retinol after bleaching in frog and mouse rod
      photoreceptor outer segments.
AB  - All-trans retinol is formed in the outer segments of vertebrate rod
      photoreceptors from the reduction of the all-trans retinal released by
      photoactivated rhodopsin. The reduction requires NADPH and is therefore dependent
      on metabolic input. In metabolically intact photoreceptors, a large increase in
      rod outer segment fluorescence, attributed to the fluorescence of all-trans
      retinol, follows rhodopsin photoactivation. The fluorescence increase is
      biphasic, including a rapid and a slow component. In metabolically compromised
      cells, there is a much smaller fluorescence increase following rhodopsin
      photoactivation, but it too contains a rapid component. We have measured the
      fluorescence signal in single living frog and mouse rod photoreceptors, and have
      characterized its dependence on the wavelengths of light selected for excitation
      and for collecting emission. We find that in metabolically intact cells, the
      excitation and emission properties of both the rapid and slow components of the
      fluorescence signal are in close agreement with those of all-trans retinol
      fluorescence. In metabolically compromised cells, however, the signal can only
      partially be due to all-trans retinol, and most of it is consistent with all
      trans retinal. The results suggest that in the outer segments of living rod
      photoreceptors there is rapid release of all-trans retinal, which in
      metabolically intact cells is accompanied by rapid conversion to all-trans
      retinol.

PMID- 20697622
TI  - Homometallic UO2(2+) diphosphonates assembled under ambient and hydrothermal
      conditions.
AB  - Four uranyl methylenediphosphonates have been synthesized from reactions of
      uranyl nitrate and methylenediphosphonate in water. Three of the compounds, (1)
      (UO(2))[CH(2)(PO(3)H)(2)](H(2)O) x 2 H(2)O, (2) (UO(2))[CH(2)(PO(3)H)(2)](H(2)O)
      x 4 H(2)O, and (3) (UO(2))[O(3)PCH(2)PO(3)H](H(2)O) x 3 H(2)O x NH(4), have been
      synthesized under ambient conditions whereas compound 4,
      (UO(2))[CH(2)(PO(3)H)(2)](H(2)O) x H(2)O, was prepared hydrothermally. Each
      compound is built from the UO(2)(2+) cation coordinated to one water molecule and
      four oxygen atoms from three diphosphonate ligands to form pentagonal bipyramid
      geometry. Despite these similarities however, compounds 1-4 exhibit remarkable
      structural diversity with 1 and 2 forming 1-D structural units, compound 3
      adopting 2-D sheets, and compound 4 exhibiting a 3-D structure. Such differences
      are attributed to variations in the preparation of the materials (reaction
      temperature and presence of counterions) as well differences in hydration and/or
      the position of the bound water molecules in each of the structures. The thermal
      and fluorescent behaviors of the compounds are also presented.

PMID- 20697623
TI  - Modulation of microRNA function by synthetic ribozymes.
AB  - MicroRNAs (miRNAs) are now recognized as one of the major class of gene
      regulatory molecules in eukaryotic cells. Aberrant miRNA expression has been
      implicated in many human diseases. Herein, we exploit the site-specific cleavage
      ability of hammerhead ribozymes to design synthetic ribozymes and establish that
      they can cleave miRNA, thereby inhibiting miRNA function. We also used modified
      ribozymes where a 3'-3'-linked nucleotide "cap" (inverted T) was added and few
      ribonucleotides were changed to 2'-O-methyl nucleotides. The modified ribozyme
      was more efficient at inhibiting miR-21 than the wild type ribozyme.

PMID- 20697624
TI  - Microwave assisted fast and facile synthesis of SnO(2) quantum dots and their
      printing applications.
AB  - An efficient synthesis of highly crystalline SnO(2) QDs with a narrow size
      distribution (4.27 +/- 0.67 nm) was achieved by microwave-assisted decomposition
      of Sn(OtBu)(4) in ionic liquid. Printed structures fabricated from SnO(2) QDs
      showed typical semiconducting I-V behaviors, and gas sensing properties.

PMID- 20697625
TI  - Recognition and regulation of unique nucleic acid structures by small molecules.
AB  - DNA and RNA are both polymorphic. Depending on the sequences and environmental
      conditions, they could exist in a variety of secondary structures that play key
      roles in many biological processes. Recognition of these structures by small
      ligands is very important for the development of new drugs and new tools. In this
      article, we will focus on recent advances in the field of molecular recognition
      and regulation of small ligands with several unique nucleic acid structures, and
      we will also highlight some of their potential applications in medicinal
      chemistry and biotechnology.

PMID- 20697626
TI  - Synthesis of an ionic liquid with an iron coordination cation.
AB  - An iron-based ionic liquid, Fe((OHCH(2)CH(2))(2)NH)(6)(CF(3)SO(3))(3), is
      synthesized in a single-step complexation reaction. Infrared and Raman data
      suggest NH(CH(2)CH(2)OH)(2) primarily coordinates to Fe(iii) through alcohol
      groups. The compound has T(g) and T(d) values of -64 degrees C and 260 degrees C,
      respectively. Cyclic voltammetry reveals quasi-reversible Fe(iii)/Fe(ii)
      reduction waves.

PMID- 20697627
TI  - Background wet deposition of mercury in Great Britain.
AB  - Precipitation samples have been collected on a monthly basis from a network of 10
      sites in Great Britain (GB) in order to estimate background mercury (Hg)
      deposition in the rural environment. Collection started in February 2005 and
      results presented here cover the period up to June 2009. The annual volume
      weighted mean (AVWM) Hg concentrations range from 1.0 ng L(-1) at Cockley Beck in
      the Lake District in 2006 to 8.8 ng L(-1) at Heigham Holmes on the Norfolk Coast
      England in 2008. The largest validated solution concentrations were 33.7 ng L(-1)
      Hg measured at Cockley Beck in May 2008. The large difference in rainfall amount
      between sites means that the remote site at Cockley Beck has both the lowest long
      term AVWM concentration (1.6 ng L(-1)) and the greatest annual flux is greatest
      at 43 mg ha(-1) yr(-1). Predicted deposition tends to be much greater in western
      Britain where the greater rainfall occurs. Because some observations are very
      close to the analytical detection limit (1.0 ng L(-1)), rigorous cleaning
      procedures, the use of replicate samplers to monitor contamination, and the
      inclusion of 'bottle blanks' are required to obtain valid measurements of Hg in
      the bulk deposition. Deposition in rural sites is equivalent to about 10% of the
      estimated magnitude of known emissions in GB.

PMID- 20697628
TI  - Spatial and temporal pattern of pesticides in the global atmosphere.
AB  - As part of the Global Atmospheric Passive Sampling (GAPS) study, XAD-resin based
      passive samplers are being deployed for consecutive one-year periods at numerous
      sites on all seven continents to determine annually averaged concentrations of
      persistent organic pollutants. Concentrations of banned organochlorine pesticides
      as well as a number of current-use pesticides in samples from the first four
      years, roughly coinciding with 2005, 2006, 2007 and 2008, show distinct spatial
      and temporal patterns. Whereas organochlorine pesticides such as alpha- and gamma
      hexachlorocyclohexane, endosulfans, DDT and its metabolites, and chlordane
      related compounds tend to be more prevalent in developing countries, especially
      in Asia, concentrations of current use pesticides such as trifluralin and
      chlorothalonil are often higher in Europe and North America. Based on 15 stations
      with four years of data, levels of hexachlorobenzene, hexachlorocyclohexanes and
      chlordanes decline in most world regions, which may reflect decreased usage in
      response to global restrictions. Levels of organochlorine pesticides in India,
      however, remain exceptionally high. Concentrations of alpha-endosulfan,
      chlorothalonil and trifluralin decrease in the European atmosphere during the
      sampling periods, indicating reduced usage. Consistently high alpha/gamma-HCH
      ratios in air samples from high Northern latitudes confirm that re-volatilization
      from the Arctic Ocean is a significant source of alpha-HCH. The highest levels of
      alpha-HCH, however, occur in conjunction with high gamma-HCH levels, suggesting
      that lindane use is now the major source of alpha-HCH to the global atmosphere.
      Although a wide variety of sampling site types aids in characterizing the entire
      global concentration variability of a pesticide, it also increases greatly the
      number of sites required for a robust regional differentiation.

PMID- 20697630
TI  - The effectiveness of essential-state models in the description of optical
      properties of branched push-pull chromophores.
AB  - In this paper we present the synthesis, spectroscopic characterization and
      theoretical modelling of two pairs of correlated dipolar and octupolar donor
      acceptor conjugated chromophores, based on the triphenylamine branching centre.
      The two pairs of chromophores differ for the electron withdrawing end-groups.
      Linear absorption, fluorescence and two-photon absorption of all the compounds in
      different solvents can be well described by the use of charge-resonance
      theoretical models based on essential-state descriptions of the electronic
      structure, and taking into account the coupling to effective molecular vibrations
      and to polar solvation degrees of freedom. On the contrary, the alternative
      Frenkel exciton model does not provide a good description of the observed
      behavior. The robustness of the proposed theoretical models is demonstrated for
      the first time by the fact that the modulation of a single molecular parameter
      (the one linked to the electron-withdrawing ability of the end groups) is enough
      to describe the evolution of the spectroscopic properties along the whole series
      of chromophores, both "intra-pair" and "inter-pair". The effectiveness of the
      approach suggests that this kind of theoretical modelling can be very useful to
      predict different properties of the compounds at hand or of correlated structures
      of increasing complexity, such as dendrons and dendrimers, giving a guide to the
      synthesis of (macro)molecules for applications in light-emitting and nonlinear
      optical devices, artificial light-harvesting systems or optical imaging of living
      tissues.

PMID- 20697631
TI  - Two-step perpendicular free-solution isoelectric focusing in a microchamber array
      chip.
AB  - A free-solution microfluidic chip device was fabricated for small-scale protein
      fractionation based on the principle of two-step perpendicular isoelectric
      focusing (IEF) previously reported in a gel slab. The microchip was composed of
      two separate glass plates with a square array of 100 indentations etched on the
      facing side of each plate. By changing the relative position of the two plates,
      ten channels can be formed as ranges of the staggered indentations and can be
      switched to the perpendicular direction, or 100 chambers of 140 nL each can be
      produced by perfect overlapping of the indentations. The entire pH range of the
      carrier ampholyte was fractionated into 10 successive pH segments in the first
      IEF, and each of the segments was further fractionated into 10 fractions by the
      second IEF at a right angle to the first one. This chip enabled IEF fractionation
      at a lower voltage and in a shorter time, compared with a linear apparatus
      operated in one direction. Fluorescence-labeled peptides with a small isoelectric
      point (pI) difference (DeltapI = 0.3) were recovered in different chambers in a
      total separation time of 10 min at a maximum applied voltage of 500 V.

PMID- 20697632
TI  - Assessment of effectiveness of the network-guided genetic screen.
AB  - Network-guided genetic screen (NGGS) has been suggested to be more effective than
      traditional forward or reverse genetics screen. Although the predictability of
      NGGS with given networks has been measured in previous studies, its general
      effectiveness, particularly for genome-wide reverse genetic screens, has not been
      assessed yet. We estimated the general effectiveness of NGGS by simulating
      iterative searching over networks for known phenotypic genes in two model
      organisms, baker's yeast (S. cerevisiae) and worm (C. elegans). We found that
      NGGS is more effective in C. elegans, implicating a higher value for NGGS in
      animals including humans.

PMID- 20697629
TI  - Designing multifunctional quantum dots for bioimaging, detection, and drug
      delivery.
AB  - The emerging field of bionanotechnology aims at revolutionizing biomedical
      research and clinical practice via introduction of nanoparticle-based tools,
      expanding capabilities of existing investigative, diagnostic, and therapeutic
      techniques as well as creating novel instruments and approaches for addressing
      challenges faced by medicine. Quantum dots (QDs), semiconductor nanoparticles
      with unique photo-physical properties, have become one of the dominant classes of
      imaging probes as well as universal platforms for engineering of multifunctional
      nanodevices. Possessing versatile surface chemistry and superior optical
      features, QDs have found initial use in a variety of in vitro and in vivo
      applications. However, careful engineering of QD probes guided by application
      specific design criteria is becoming increasingly important for successful
      transition of this technology from proof-of-concept studies towards real-life
      clinical applications. This review outlines the major design principles and
      criteria, from general ones to application-specific, governing the engineering of
      novel QD probes satisfying the increasing demands and requirements of
      nanomedicine and discusses the future directions of QD-focused bionanotechnology
      research (critical review, 201 references).

PMID- 20697633
TI  - Ordered mesoporous materials as solid supports for rhodium-diphosphine catalysts
      with remarkable hydroformylation activity.
AB  - A rhodium-diphosphine complex based on Xantphos-type ligands was anchored on
      mesoporous silica SBA-15, and the material showed remarkably high catalytic
      activity in the hydroformylation of 1-octene, even exceeding its homogeneous
      analogue under certain conditions.

PMID- 20697634
TI  - SHG-active molecular nanorods with intermediate photochromic properties compared
      to solution and bulk solid states.
AB  - A convenient protocol has been developed to fabricate well-defined nanorods of a
      photochromic molecule N-(3,5-di-tert-butylsalicylidene)-4-aminopyridine (DBSAP)
      by a laser ablation method. Reversible and fatigue-resistant optical switching
      and SHG activity were demonstrated. Interestingly, it was observed that DBSAP
      nanorods exhibit intermediate photochromic properties compared to solution and
      solid.

PMID- 20697635
TI  - Solid-liquid interface synthesis of microcrystalline porous coordination
      networks.
AB  - Solid-liquid interface synthesis provided a unique way to selectively and
      efficiently prepare molecular complexes (ML(2)) and metastable porous
      coordination networks in short crystallization times. In sharp contrast, their
      solution reactions gave interpenetrated open-framework networks. We succeeded in
      solving a crystal structure of the metastable network by ab initio powder X-ray
      analysis.

PMID- 20697636
TI  - Silver triflate and N-heterocyclic carbene co-catalyzed reaction of N'-(2
      alkynylbenzylidene)hydrazide, methanol with alpha,beta-unsaturated aldehyde.
AB  - A highly efficient silver triflate and N-heterocyclic carbene co-catalyzed three
      component reaction of N'-(2-alkynylbenzylidene)hydrazide, methanol with
      alpha,beta-unsaturated aldehyde is described, which gives rise to the 2-amino-1,2
      dihydroisoquinolines in good yield.

PMID- 20697637
TI  - Visible light-driven water oxidation catalyzed by a highly efficient dinuclear
      ruthenium complex.
AB  - Visible light-driven water oxidation has been achieved by the dinuclear ruthenium
      complex 1 with a high turnover number of 1270 in a homogeneous system in the
      presence of a Ru polypyridine complex photosensitizer.

PMID- 20697638
TI  - Nuclearity of nickel and mixed sodium-nickel complexes: dependence on the spacer
      in chelating pyridine-alcoholate ligands.
AB  - Modifying the HL/Ni(ii) stoichiometry in the reaction between pyridine-2
      ylmethanol (HL), [NiCl(2)(DME)] and NaH affords [Na(3)Ni(4)L(9)(mu(3)-OH)]Cl (1)
      or the new, unusual Na(10)Ni(6) polynuclear complex
      [Na(8)(NaL)(2)(NiL(3))(6)(mu(5)-OH)(2)] (2); starting from pyridine-2-ylethanol
      (HL(Et)) instead yielded [Ni(3)(mu-L(Et))(2)(mu(3)-L(Et))(2)(L(Et))(HL(Et))]Cl,
      whose magnetic properties are reported.

PMID- 20697639
TI  - Highly regio- and enantioselective catalytic asymmetric hydroboration of alpha
      substituted styrenyl derivatives.
AB  - The catalytic asymmetric hydroboration of a variety of 1,1-disubstituted olefins
      has been achieved with excellent yields, perfect regioselectivity and in some
      cases, high levels of enantioselectivity using readily accessible iridium
      catalyst.

PMID- 20697640
TI  - Pt-free cathode catalysts prepared via multi-step pyrolysis of Fe phthalocyanine
      and phenolic resin for fuel cells.
AB  - Pt-free cathode catalysts for polymer electrolyte membrane fuel cells have been
      prepared by multi-step pyrolysis of FePc and PhRs, in the best of which show
      extensively high initial cell performance and good durability compared to other
      present precious-metal-free cathode catalysts to date.

PMID- 20697641
TI  - Synthesis and thermal responsiveness of self-assembled gold nanoclusters.
AB  - A simple and versatile approach was developed to generate hierarchical assemblies
      of ultra-small gold nanocluster thin films using the combination of galvanic
      reaction and a block copolymer coordinated with gold complex. Variation of the
      temperature allows effective control over the optical response of these stimuli
      responsive organic-nanocluster hybrid structures.

PMID- 20697642
TI  - Making a [Co24] metallamacrocycle from the shuttlecock-like tetranuclear cobalt
      calixarene building blocks.
AB  - A [Co(24)] metallamacrocycle with a [36-MC(Co)-12] periphery and an inner [24
      MC(Co)-6] rim is constructed by linking six Co(4)-thiacalixarene shuttlecock-like
      SBUs with twelve 1,2,4-triazole molecules.

PMID- 20697643
TI  - Detecting protein interactions in live cells via complementation of a hydrolysis
      deficient beta-lactamase.
AB  - Protein-fragment complementation assay using a hydrolysis-deficient beta
      lactamase provides a robust tool for studying protein-protein interactions.

PMID- 20697644
TI  - Strong ferromagnetic metal-ligand exchange in a nickel bis(3,5-dipyridylverdazyl)
      complex.
AB  - A new 1,5-dipyridyl verdazyl, synthesized from the corresponding dipyridyl
      hydrazone, coordinates nickel(ii) to form a structurally characterized,
      pseudooctahedral complex analogous to Ni(terpy)(2)(2+). The unusually short Ni
      verdazyl distance results in strong ferromagnetic exchange (J(Ni-rad) = +300,
      J(rad-rad) = +160 cm(-1)) between all three paramagnetic species along with a
      metal-ligand charge transfer band in the electronic spectrum.

PMID- 20697645
TI  - An approach to bimetallic catalysts by ligand design.
AB  - New diphosphines based on benzofurobenzofuran and dibenzodioxocin backbones,
      forming exclusively bimetallic complexes were designed and synthesized. Depending
      on the ligand to metal ratio, face-to-face bimetallic complexes or syn-chloride
      bridged dimeric complexes were formed as main reaction products. The structures
      of the rhodium complexes of the new ligands 4, 7, 10, 13, 16 were established in
      solution by NMR, IR, and MS spectroscopy. The molecular structures of the syn
      chloride bridged dimeric complexes [Rh(2)(CO)(2)(mu-Cl)(2)(4)] (22),
      [Rh(2)(CO)(2)(mu-Cl)(2)(10)] (24), and the face-to-face bimetallic complexes
      [Rh(CO)Cl(4)](2) (17), [Rh(CO)Cl(10)](2) (19), and [Rh(CO)Cl(13)](2) (20) were
      confirmed by X-ray crystallography. Ligands 4, 7, 10, 13, 16, and SPANphos were
      tested in rhodium catalyzed methanol carbonylation at 150 degrees C and 22 bar of
      CO gas, showing high activities under catalytic conditions.

PMID- 20697646
TI  - The gas-phase structure and some reactions of the bulky primary silane
      (Me(3)Si)(3)CSiH(3) and the solid-state structure of the bulky dialkyl disilane
      [(Me(3)Si)(3)CSiH(2)](2).
AB  - The molecular structure of the bulky primary silane, (Me(3)Si)(3)CSiH(3), in the
      gas phase has been determined by electron diffraction. Photolysis of
      (Me(3)Si)(3)CSiH(3) affords a convenient route to the bulky dialkyl disilane,
      [(Me(3)Si)(3)CSiH(2)](2), which is the first 1,2-dialkyldisilane to be
      structurally characterised by single-crystal X-ray diffraction. The disilane has
      an unusually large Si-Si-C angle of 120.05(9) degrees .

PMID- 20697647
TI  - Fabrication of polypyrrole/ZnCoO nanohybrid systems for solar cell applications.
AB  - Hybrid solar cells employing conjugated polymers have revolutionized the
      photovoltaic industry by offering the prospect for large-scale energy conversion
      applications through cost-effective fabrication techniques. In this regard, we
      have demonstrated an experimental approach to fabricate polypyrrole/ZnCoO nanorod
      hybrid systems, using hydrothermal and electropolymerization techniques. The
      structural property studies on the hydrothermally synthesized Co-doped ZnO
      nanocrystallites revealed them to be phase pure with rod-like morphology.
      Considering the significant enhancement in their absorbance values over the
      visible spectral range (possibility for extended photon absorption), ZnCoO
      (Zn(0.95)Co(0.05)O) nanorods were deposited on transparent conducting (FTO)
      substrates through dip-coating methodology, for the fabrication of working
      electrodes. Electropolymerization of the pyrrole monomers was then carried out on
      the fabricated electrodes through cyclic voltammetry. The formation of polymer
      material was verified using FT-IR spectroscopy. The morphological evolution of
      polypyrrole deposits and their distribution on the working electrodes were
      substantially studied using atomic force microscopy and scanning electron
      microscopy. The flat band potential for the hybrid systems assimilated from the
      Mott-Schottky plots was observed to shift towards negative direction compared
      with ZnCoO, presumably due to the presence of the polymer composites, which gives
      rise to a more negative potential.

PMID- 20697648
TI  - Photoactive binary and ternary lanthanide (Eu3+, Tb3+, Nd3+) hybrids with p-tert
      butylcalix[4]arene derived Si-O linkages and polymers.
AB  - Through the reaction between the hydroxyl groups of p-tert-butylcalix[4]arene
      derivatives (Calix-Br, Calix-AC) and the isocyanate group of 3-(triethoxysilyl)
      propyl isocyanate (TEPIC), two novel kinds of functional polysilsesquioxanes
      linkage precursors Calix-Br-Si and Calix-AC-Si have been synthesized. Then the
      binary and ternary hybrid materials are assembled with chemical bonds, which are
      composed of lanthanide ion centres (Eu(3+), Tb(3+), Nd(3+)), precursors Calix-Br
      Si or Calix-AC-Si and the organic polymers [poly(4-vinylpyridine) (PVPD) or
      poly(methyl methacrylate) (PMMA)]. The composition and physical properties of
      these hybrids are characterized, especially comparing the photoluminescent
      characters. It is found that the hybrids with modified p-tert-butylcalix[4]arene
      derivative units show better photoluminescent properties than pure original p
      tert-butylcalix[4]arene units or lanthanide complexes. Besides, introduction of
      polymer chain is favorable for the thermal stability, regular microstructure and
      luminescence of hybrid systems. Among the europium hybrids, the hybrids
      containing the polymer PMMA possesses the longest lifetime and highest quantum
      efficiency.

PMID- 20697649
TI  - Amido phosphine complexes of zinc: synthesis, structure, and catalytic ring
      opening polymerization of epsilon-caprolactone.
AB  - A series of diarylamido phosphine ligands of the type N-(2
      dihydrocarbylphosphinophenyl)-2,6-dialkylanilide 1a-d have been prepared and
      employed to investigate the coordination chemistry of zinc. Protonolysis of ZnMe2
      with one equivalent of N-(2-diphenylphosphinophenyl)-2,6-dimethylaniline (H[1a])
      produced a mixture of [1a]ZnMe (2a) and Zn[1a]2 (4a), whereas that involving
      ZnEt2 gave exclusively the three-coordinate [1a]ZnEt (3a). In contrast, treatment
      of ZnR2 (R = Me, Et) with N-(2-diphenylphosphinophenyl)-2,6-diisopropylaniline
      (H[1b]), N-(2-diisopropylphosphinophenyl)-2,6-dimethylaniline (H[1c]), or N-(2
      diisopropylphosphinophenyl)-2,6-diisopropylaniline (H[1d]) under similar
      conditions generated quantitatively the corresponding three-coordinate zinc
      methyl 2b-d and zinc ethyl 3b-d. The bis-ligand complexes 4a,b,d were isolated by
      either protonolysis of alkyls 2-3 with one equivalent of H[1] or metathesis of
      ZnX2 (X = Cl, OAc) with the corresponding lithium derivatives 5. Attempts to
      prepare [1a-d]ZnX (X = Cl, OAc) were not successful regardless of stoichiometry
      of the starting materials employed. Alcoholysis of zinc alkyls 2-3 led
      undesirably to protonation on the amido nitrogen donor of 1, highlighting perhaps
      its higher basicity than alkyls. The reaction of ZnCl2 with H[1c] generated the
      phosphorus-bound adduct {H[1c]ZnCl(mu-Cl)}2 (6c). Interestingly, attempts to
      deprotonate 6c with n-BuLi produced unexpectedly the alkylated product [1c]Zn(n
      Bu) (7c) instead of [1c]ZnCl; analogous reactions employing NEt3 led to Lewis
      base substitution to give H[1c] and [ZnCl2(NEt3)]2. Structural characterization
      of all new compounds was achieved by multi-nuclear NMR spectroscopy (1H, 13C,
      31P, and 7Li) and X-ray crystallography (2c-d, 3c, 4d, 5c-d, and 6c) where
      appropriate. On the basis of the NMR and X-ray data, in combination with the
      synthetic investigations, the steric nature of these amido phosphine ligands is
      recognized to follow the order of 1a < 1b < 1c < 1d. Interestingly, zinc alkyls 2
      3 are all active initiators for catalytic ring-opening polymerization of epsilon
      caprolactone whereas the bis-ligand complexes 4 are not.

PMID- 20697650
TI  - A robust nanofluidic membrane with tunable zero-order release for implantable
      dose specific drug delivery.
AB  - This manuscript demonstrates a mechanically robust implantable nanofluidic
      membrane capable of tunable long-term zero-order release of therapeutic agents in
      ranges relevant for clinical applications. The membrane, with nanochannels as
      small as 5 nm, allows for the independent control of both dosage and mechanical
      strength through the integration of high-density short nanochannels parallel to
      the membrane surface with perpendicular micro- and macrochannels for interfacing
      with the ambient solutions. These nanofluidic membranes are created using
      precision silicon fabrication techniques on silicon-on-insulator substrates
      enabling exquisite control over the monodispersed nanochannel dimensions and
      surface roughness. Zero-order release of analytes is achieved by exploiting
      molecule to surface interactions which dominate diffusive transport when fluids
      are confined to the nanoscale. In this study we investigate the nanofluidic
      membrane performance using custom diffusion and gas testing apparatuses to
      quantify molecular release rate and process uniformity as well as mechanical
      strength using a gas based burst test. The kinetics of the constrained zero-order
      release is probed with molecules presenting a range of sizes, charge states, and
      structural conformations. Finally, an optimal ratio of the molecular hydrodynamic
      diameter to the nanochannel dimension is determined to assure zero-order release
      for each tested molecule.

PMID- 20697651
TI  - Converting carbon nanofibers to carbon nanoneedles: catalyst splitting and
      reverse motion.
AB  - Carbon nanoneedles (CNNs) were grown using a plasma-enhanced chemical vapor
      deposition process in which the source gas (C(2)H(2)) was turned off 10 min
      before the NH(3) flow and plasma were turned off. It is demonstrated that tubular
      carbon nanofibers (CNFs) grow while the source gas is on. However, once the
      source gas is turned off, the Ni catalyst at the top of each CNF splits to form a
      small catalyst that remains at the top of the tube and a larger catalyst that
      travels down the interior of the tube. We postulate that the motion of the bottom
      (larger) catalyst is driven by etching of the graphitic walls and 'cups' inside
      the CNF. This process, combined with slowing growth of the CNFs and etching of
      the material above the bottom catalyst, converts the carbon nanofibers to the
      final nanoneedle shape.

PMID- 20697652
TI  - Amplified energy transfer in conjugated polymer nanoparticle tags and sensors.
AB  - Nanoparticles primarily consisting of pi-conjugated polymers have emerged as
      extraordinarily bright fluorescent tags with potential applications in biological
      imaging and sensing. As fluorescent tags, conjugated polymer nanoparticles
      possess a number of advantageous properties, such as small particle size,
      extraordinary fluorescence brightness, excellent photostability, and high
      emission rate. Exciton diffusion occurring in the nanoparticles results in
      amplified energy transfer, doubling the energy transfer efficiency in some cases.
      Amplified energy transfer has been exploited to obtain highly red-shifted
      emission, oxygen-sensing nanoparticles, and fluorescence photoswitching.
      Additional observed phenomena are attributable to amplified energy transfer in
      conjugated polymers, including superquenching by metal nanoparticles, and
      fluorescence modulation by hole polarons. This feature article presents an
      overview of recent investigations of optical properties and energy transfer
      phenomena of this relatively novel type of fluorescent nanoparticle with a
      viewpoint towards demanding fluorescence-based imaging and sensing applications.

PMID- 20697653
TI  - Stereoselective synthesis of the bicyclic guanidine alkaloid (+)-monanchorin.
AB  - A new approach for the stereoselective synthesis of the bicyclic guanidine
      alkaloid (+)-monanchorin has been developed using a palladium(ii)-catalysed MOM
      ether directed Overman rearrangement to establish the second stereogenic centre
      and a cross metathesis reaction to generate the carbon backbone. In the final
      stage, a one-pot acid mediated deprotection of aldehyde, guanidine and hydroxyl
      groups gave an intermediate that underwent facile cyclisation to (+)-monanchorin.

PMID- 20697654
TI  - Rhodamines in the gas phase: cations, neutrals, anions, and adducts with metal
      cations.
AB  - Optical spectroscopy of biological molecules in the gas phase has recently gained
      considerable attention, being able to provide complementary structural
      information in the absence of native matrix. Biomolecules can change their
      properties when brought into the gas phase, and so can chromophores associated
      with them. Understanding the photophysics of chromophore labels is central for
      the correct interpretation of experimental data. In this report, the structure
      and the optical properties of Rhodamine 19 (R19) in the gas phase were examined
      by a combination of Fourier-transform ion cyclotron resonance mass spectrometry
      and visible-light laser spectroscopy. While R19 in solution is found either in
      neutral (R19(n)) or protonated (R19+H(+)) forms, other structures can be
      generated in the gas phase, such as anions (R19-H(-)) and adducts with metal
      cations (R19+M(+)). Experimental evidence for the lactone structure of neutral
      gas-phase R19 is presented for the first time. The different properties of gas
      phase compared to solution-phase R19 are discussed in view of structural analysis
      of labeled gas-phase biological molecules by optical spectroscopy.

PMID- 20697655
TI  - A dynamic microarray device for paired bead-based analysis.
AB  - In this study, we have developed a meander-shaped dynamic microfluidic technology
      that allows us to pair two different types of microbeads in a trapping site. The
      dynamic microfluidic technology comprises implemented modifications of a
      conventional dynamic microarray design such as: (i) the combination of a meander
      shaped by-pass channel and a trapping channel with a hydrodynamic trapping site
      and (ii) line-symmetrical formation of the by-pass and trapping channels. Using
      these modifications, we have successfully trapped different types of sample in
      one trapping site, and constructed an array of paired beads of different type
      such as polystyrene beads or hydrogel beads made of agarose, collagen or
      alginate. We found that this meander-shaped dynamic microfluidic technology is
      applicable for the observation of interactions between the paired beads such as
      molecular diffusion.

PMID- 20697657
TI  - 2-Dimensional micro-network of boron-doped diamond film: fabrication and
      electrochemical sensing application.
AB  - By means of delicate and conventional methods based on photolithography and hot
      filament chemical vapor deposition (HFCVD) technology, a novel boron-doped
      diamond micro-network (BDDMN) film was fabricated, and this micro-structure
      showed excellent electrochemical sensing properties.

PMID- 20697656
TI  - Galvanic reactions involving silver nanoparticles embedded in cation-exchange
      membrane.
AB  - Galvanic reactions of Hg(2+), Rh(3+), and AuCl(4)(-) ions with Ag nanoparticles
      positioned near the surface and throughout the matrix of host
      poly(perfluorosulfonic) acid membrane have been studied.

PMID- 20697658
TI  - Self-adaptive hydrophilic and coordinating Teflon surfaces through a
      straightforward physisorption process.
AB  - Teflon surfaces exhibiting self-adaptive behaviour with both highly hydrophilic
      character and strong coordinating properties are prepared in a straightforward
      manner by physisorption of the fluorophilic copper(II)-carboxylate complex 2.

PMID- 20697659
TI  - Adsorption of human insulin on single-crystal gold surfaces investigated by in
      situ scanning tunnelling microscopy and electrochemistry.
AB  - We have explored the adsorption of zinc-free human insulin on the three low-index
      single-crystalline Au(111)-, Au(100)- and Au(110)-surfaces in aqueous buffer
      (KH(2)PO(4), pH 5) by a combination of electrochemical scanning tunnelling
      microscopy (in situ STM) at single-molecule resolution and linear sweep, LSV,
      cyclic, CV, and square wave (SQWV) voltammetry.Multifarious electrochemical
      patterns were observed. Most attention was given to reductive desorption caused
      by insulin binding to the Au-surfaces via up to three disulfide groups per
      insulin monomer, presumably converted to single Au-S links. SQWV suggested the Au
      S bond strength order Au(111) > Au(110) > Au(100) based on the reductive
      desorption potentials. The voltammetric diversity was paralleled by different in
      situ STM insulin adsorption modes on the three surfaces. Single-molecule
      resolution was achieved in all cases. The coverage followed the order Au(110) >
      Au(100) > Au(111) and differs from the reductive desorption order that records
      the Au-S bonding element. Evenly distributed single molecules were scattered over
      large Au(111)-terraces, with intriguing molecular arrays disclosed near the
      terrace edges. In comparison, high-density molecular scale structures were
      observed both over the terraces and across terrace edges on Au(100). Larger
      rectangular structures also appeared (8-12% coverage). These are Au-islands from
      the lift of the reconstruction. Notably, 10 x 10 nm(2) patches of highly ordered
      much smaller structures, possibly from insulin decomposition emerged sporadically
      within the dense insulin adlayer. Insulin adsorbed in highest coverage on the
      Au(110) and followed the directional surface topology with insulin molecules
      aligned in the Au(110)-surface grooves, occasionally "spilling over" and merging
      into larger structures.Adsorption, Au-S binding, and insulin unfolding are all
      parts of insulin surface behaviour and reflected in both voltammetry and in situ
      STM. In spite of these complications, the data show that molecular scale
      resolution has been achieved and offer other perspectives of insulin surface
      science such as single-molecule mapping of the insulin monomer/dimer-hexamer
      interconversion.

PMID- 20697660
TI  - Defect crystal structure of new TiO(OH)2 hydroxide and related lithium salt
      Li2TiO3.
AB  - Crystal structures of TiO(OH)(2) and Li(2)TiO(3) have been studied in detail and
      refined using X-ray powder diffraction data. Both compounds possess a high
      concentration of defects in the structure. The crystal structure of the
      Li(2)TiO(3) salt obtained at 700 degrees C reveals stacking faults of LiTi(2)
      metal layers, which leads to the appearance of short-range order in three
      possible space groups: C2/c, C2/m, P3(1)12. The possibility to stabilise this
      imperfect state increases the mobility of the Li(+) ions in the structure and
      allows the complete exchange of lithium by hydrogen in acid water solutions with
      formation of TiO(OH)(2). The crystal structure of TiO(OH)(2) belongs to the
      layered double hydroxide structure type with the 3R(1) sequence of oxygen layers
      and can be described as a stacking of charge-neutral metal oxyhydroxide slabs
      [(OH)(2)OTi(2)O(OH)(2)]. TiO(OH)(2) is the first layered double hydroxide
      structure formed by a cation with oxidation state +4 only.

PMID- 20697661
TI  - Ionic liquid-based compound droplet microfluidics for 'on-drop' separations and
      sensing.
AB  - We present a new and general scheme for analytical applications of droplet-based
      microfluidics in which flowing droplets function not only as isolated reaction
      flasks, but are also capable of on-drop separation and sensing. To demonstrate
      this, we choose ionic liquids as designer fluids whose chemical and physical
      properties can be tailored in task-specific fashion. We create aqueous-ionic
      liquid compound droplets with tunable structures using an imidazolium-based ionic
      liquid, and present two analytical applications-separation of a binary aqueous
      mixture of organic dyes and dynamic pH sensing-to highlight the salient features
      of this scheme. By combining designer fluids with designer microfluidic
      emulsions, our work opens up a rich space of exploration for analytical
      microfluidics.

PMID- 20697662
TI  - Tunable two-dimensional liquid gradient refractive index (L-GRIN) lens for
      variable light focusing.
AB  - We report a two-dimensional (2D) tunable liquid gradient refractive index (L
      GRIN) lens for variable focusing of light in the out-of-plane direction. This
      lens focuses a light beam through a liquid medium with a 2D hyperbolic secant
      (HS) refractive index gradient. The refractive index gradient is established in a
      microfluidic chamber through the diffusion between two fluids with different
      refractive indices, i.e. CaCl(2) solution and deionized (DI) water. The 2D HS
      refractive index profile and subsequently the focal length of the L-GRIN lens can
      be tuned by changing the ratio of the flow rates of the CaCl(2) solution and DI
      water. The focusing effect is experimentally characterized through side-view and
      top-view image analysis, and the experimental data match well with the results
      from ray-tracing optical simulations. Advantages of the 2D L-GRIN lens include
      simple device fabrication procedure, low fluid consumption rate, convenient lens
      tuning mechanism, and compatibility with existing microfluidic devices. We expect
      that with further optimizations, this 2D L-GRIN lens can be used in many optics
      based lab-on-a-chip applications.

PMID- 20697663
TI  - Novel binaphthyl-containing bi-nuclear boron complex with low concentration
      quenching effect for efficient organic light-emitting diodes.
AB  - OLEDs employing CMB1, a novel binaphthyl-containing bi-nuclear boron complex, as
      the emitter exhibited bright yellow emission with a luminous efficiency of 2.1 cd
      A(-1).

PMID- 20697664
TI  - Product-selectivity control by the nature of the catalyst: Lewis acid-catalyzed
      selective formation of ring-fused tetrahydroquinolines and tetrahydroazepines via
      intramolecular redox reaction.
AB  - Selective synthesis of ring-fused tetrahydroquinolines and tetrahydroazepines
      from the same starting materials was achieved by subtle use of the oxophilic
      Sc(OTf)(3) or carbophilic IPrAuOTf as the catalyst.

PMID- 20697665
TI  - Guest induced transformations of assembled pyridyl bis-urea macrocycles.
AB  - Pyridine macrocycles with no cavities assembled into close packed columns yet
      absorbed guests including hydrogen, carbon dioxide, and iodine.

PMID- 20697666
TI  - Alzheimer's disease-the inexorable epidemic.

PMID- 20697667
TI  - Epidemiological characteristics of cholera in Singapore, 1992-2007.
AB  - INTRODUCTION: We carried out an epidemiological review of cholera in Singapore to
      determine its trends and the factors contributing to its occurrence. MATERIALS
      AND METHODS: Epidemiological data of all notified cases of cholera maintained by
      the Communicable Diseases Division, Ministry of Health, for the period 1992 to
      2007 were collated and analysed. Case-control studies were carried out in
      outbreaks to determine the source of infection and mode of transmission. Linear
      patterns in age and ethnic distribution of cholera cases were assessed using chi2
      test for trend. RESULTS: There were a total of 210 cholera cases reported between
      1992 and 2007. The incidence of cholera declined from 17 cases in 1992 to 7 cases
      in 2007. About a quarter of the cases were imported from endemic countries in the
      region. Between 76% and 95% of the reported cases were local residents. Four
      elderly patients with comorbidities and who sought medical treatment late died,
      giving a case-fatality rate of 1.9%. Vibrio cholerae 01, biotype El Tor, serotype
      Ogawa, accounted for 83.8% of the cases. The vehicles of transmission identified
      in outbreaks included raw fi sh, undercooked seafood and iced drinks cross
      contaminated with raw seafood. CONCLUSION: With the high standard of
      environmental hygiene and sanitation, a comprehensive epidemiological
      surveillance system and licensing and control of food establishments, cholera
      could not gain a foothold in Singapore despite it being situated in an endemic
      region. However, health education of the public on the importance of personal and
      food hygiene is of paramount importance in preventing foodborne outbreaks.
      Physicians should also maintain a high level of suspicion of cholera in patients
      presenting with severe gastroenteritis, especially those with a recent travel
      history to endemic countries.

PMID- 20697668
TI  - Timing of arrival to a tertiary hospital after acute ischaemic stroke - A follow
      up survey 5 years later.
AB  - INTRODUCTION: Intravenous tissue plasminogen activator (tPA) within 3 hours of
      stroke onset is a licensed proven therapy for ischaemic stroke, with recent trial
      data showing benefit up to 4.5 hours. We previously published in this journal
      data of a survey conducted in 2004 showing only 9% of ischaemic stroke patients
      presenting to the Singapore General Hospital (SGH) arrived within 2 hours of
      onset. We aimed to determine whether the problem of delayed hospital arrival
      persists in 2009 and to establish the impact of widening the time window for
      intravenous tPA to 4.5 hours. MATERIALS AND METHODS: We prospectively surveyed
      consecutive ischaemic stroke patients admitted to the SGH from 9th March to 30th
      April 2009. Patients and/or relatives were interviewed with a standardised form
      similar to the 2004 survey. RESULTS: Among the 146 ischaemic stroke patients
      surveyed (median age 67 years, 59% male, median NIHSS score 2), 6% presented to
      SGH within 2 hours and 15% within 3.5 hours of onset. Median time from stroke
      onset to hospital arrival was 1245 minutes (20.75 hours). Pre-hospital
      consultation was significantly associated with hospital arrival after 2 hours
      from onset. Main reasons cited for delay were not realising the gravity of
      symptoms (31%) and not recognising them as stroke (27%). CONCLUSION: Delayed
      arrival to SGH following acute ischaemic stroke remains a problem in 2009. This
      confirms the lack of stroke awareness in Singapore and highlights the need for
      public stroke education. Furthermore, these data confirm that widening the time
      window for intravenous tPA treatment to 4.5 hours at SGH will increase its
      utilisation.

PMID- 20697669
TI  - Intraretinal segmentation on fourier domain optical coherence tomography.
AB  - INTRODUCTION: We studied the automated intraretinal segmentation on Fourier
      domain optical coherence tomography (OCT). MATERIALS AND METHODS: Thirty eyes
      from 30 normal subjects were studied using the RTVue-100. Both radial and raster
      scan protocol were performed 3 times on each subject. The OCT software performs
      automated intraretinal segmentation and provides macular thickness measurements.
      RESULTS: Both scanning protocols provide reproducible inner, outer and full
      retinal thickness measurements. The inner, outer and full retinal thicknesses at
      the foveal central subfield were 67.31 +/- 12.27 microm, 151.67 +/- 12.96 microm,
      219.33 +/- 23.19 microm, respectively by the raster scan, and 63.27 +/- 10.37
      microm, 147.07 +/- 14.54 microm, 209.89 +/- 21.80 microm, respectively by the
      radial scan. Macular regional variations were consistently observed. The raster
      scan protocol gives greater retinal thickness measurements than the radial scan
      protocol (P <0.05), but the latter yields slightly more reproducible results.
      CONCLUSIONS: Fourier domain OCT equipped with the ability to perform automatic
      intraretinal segmentation is a convenient tool in studying diseases that may
      differentially affect various parts of the retina. However, the establishment of
      normative values can be complicated by different scanning protocols, devices
      used, methods of data presentation and definition of intraretinal boundaries.

PMID- 20697670
TI  - Peripheral arterial disease in community-based patients with diabetes in
      Singapore: Results from a Primary Healthcare Study.
AB  - INTRODUCTION: Peripheral arterial disease (PAD) is an important complication of
      diabetes mellitus (DM), significantly associated with increased morbidity and
      mortality secondary to amputations, strokes and coronary artery disease.
      Information on DM patients with PAD is limited in our ethnically diverse
      population in Singapore. We aimed to determine the prevalence, risk factors and
      co-morbidities of PAD in patients managed for DM in the primary care setting.
      MATERIALS AND METHODS: A cross-sectional study was conducted among 521 diabetics
      in 9 of the 18 government-aided clinics in the community. Data including
      demographics, presence of co-morbidities and vascular risk factors were collected
      using an interviewer-administered questionnaire, and Ankle-Brachial Index (ABI)
      was calculated from systolic ankle and brachial pressure measurements. RESULTS:
      The prevalence of PAD, defi ned as resting ABI of <0.9 on either leg and/or a
      history of gangrene or non-traumatic amputation was 15.2% [95% confidence
      interval (CI), 12.3-18.5]. This prevalence of PAD was higher in patients with pre
      existing microvascular and other macrovascular complications. In multivariate
      analysis, prevalence of PAD was positively associated with increasing age (OR,
      1.08; 95% CI, 1.05-1.12), Malay versus Chinese ethnicity (OR, 2.27; 95% CI, 1.09
      4.70), low HDL-cholesterol (OR, 1.87; 95% CI, 1.04- 3.37), and insulin treatment
      (OR, 2.98; 95%CI, 1.39-6.36). CONCLUSION: PAD is an important cause of concern
      among patients with diabetes, with a high prevalence which further increases with
      increasing age and duration of DM, and exhibits ethnic variation. Risk factors
      identified in this study may improve early identification of PAD, allowing for
      prompt interventions, with a potential to reduce long-term morbidity and
      mortality.

PMID- 20697671
TI  - Evaluation on the effectiveness of the national childhood immunisation programme
      in Singapore, 1982-2007.
AB  - INTRODUCTION: We undertook a study to evaluate the effectiveness of the National
      Childhood Immunisation Programme (NCIP) over the past 26 years by reviewing the
      epidemiological trends of the diseases protected, the immunisation coverage and
      the changing herd immunity of the population during the period of 1982 to 2007.
      MATERIALS AND METHODS: The epidemiological data of all cases of diphtheria,
      pertussis, poliomyelitis, measles, mumps, rubella and acute hepatitis B notified
      to the Communicable Diseases Division, Ministry of Health (MOH) from 1982 to 2007
      were collated and analysed. Data on tuberculosis (TB) cases were obtained from
      the TB Control Unit, Tan Tock Seng Hospital. Cases of neonatal tetanus and
      congenital rubella syndrome (CRS) among infants born in Singapore were identified
      from the Central Claims Processing System. The number of therapeutic abortions
      performed for rubella infections was retrieved from the national abortion
      registry. Coverage of the childhood immunisation programme was based on the
      immunisation data maintained by the National Immunisation Registry, Health
      Promotion Board. To assess the herd immunity of the population against the
      various vaccine-preventable diseases protected, the findings of several
      serological surveys conducted from 1982 to 2005 were reviewed. RESULTS: The
      incidence of vaccine-preventable diseases covered under the NCIP had declined
      over the last 26 years with diphtheria, neonatal tetanus, poliomyelitis and
      congenital rubella virtually eliminated. The last case of childhood TB meningitis
      and the last case of acute hepatitis B in children below 15 years were reported
      in 2002 and 1996, respectively. CONCLUSION: The NCIP has been successfully
      implemented as evidenced by the disappearance of most childhood diseases,
      excellent immunisation coverage rate in infants, preschool and school children,
      and high level of herd immunity of the childhood population protected.

PMID- 20697672
TI  - An eight year review of exercise-related cardiac arrests.
AB  - INTRODUCTION: Exercise-related cardiac arrest is uncommon, however it is
      devastating when it occurs in otherwise healthy adults. This study aims to
      identify the characteristics of exercise-related cardiac arrest in the study
      population and estimate the overall survival rate. MATERIALS AND METHODS: This is
      a retrospective observational study of exercise-related cardiac arrest in
      Singapore. Patients with exercise-related out of hospital cardiac arrest (OHCA)
      were selected from the Cardiac Arrest and Resuscitation Epidemiology (CARE)
      database, which is a prospective cardiac arrest registry, derived from ambulance
      records, emergency department and hospital discharge records. Patient
      characteristics, cardiac arrest circumstances and outcomes were studied. RESULTS:
      Fifty-fi ve cases of exercise-related cardiac arrests were identified from
      December 2001 to January 2008. Mean age was 50.9 years with a male predominance
      of 96.4%. Eighty percent of the exercise-related cardiac arrests were witnessed,
      however only 58.2% of the patients received bystander cardiopulmonary
      resuscitation (CPR). The fi rst presenting rhythm was ventricular fibrillation
      (VF) in 40% of the patients, followed by asystole (38.2%). Of 96.2% of the
      patients who died from cardiac causes, coronary artery disease was the main
      etiology for 54%. The 30-day survival rate was 5.5%. CONCLUSION: We found that
      exercise-related cardiac arrest causes significant mortality in our community.
      Increased CPR training among the public, easy access to defibrillators and faster
      emergency medical service (EMS) response time could improve the outcome of
      exercise-related cardiac arrests. A comprehensive pre-participation screening for
      competitive exercises should be outlined for primary prevention of exercise
      related cardiac arrest. A better reporting system for exercise-related cardiac
      arrest is needed.

PMID- 20697673
TI  - Phosph-Akt1 expression is associated with a favourable prognosis in pancreatic
      cancer.
AB  - INTRODUCTION: Akt, a serine/threonine protein kinase, mediates growth factor
      associated cell survival. In several human cancers, including pancreatic cancer,
      constitutive activation of Akt (phosphorylated Akt, p-Akt) has been observed and
      may be associated with chemotherapy and radiotherapy resistance. However, there
      are contradictory viewpoints in p-Akt in pancreatic cancer on prognosis, and the
      clinical relevance of p-Akt in pancreatic cancer is not well understood. This
      study aims to investigate the expressions and relevance of Akt and p-Akt1 in
      pancreatic cancer tissues and their clinical significance. MATERIALS AND METHODS:
      The expressions of Akt and p-Akt in 74 surgically resected paraffin-embedded
      pancreatic ductal adenocarcinoma samples and 10 normal pancreatic tissue samples
      were examined by immunohistochemistry. The associations of their expression with
      clinicopathological and survival data were analysed. RESULTS: The positive
      expression rate of Akt and p-Akt1 were 87.8% and 83.8%, respectively, which were
      remarkably higher then those in normal pancreatic tissue (P <0.05). There was a
      positive correlation between the expression of Akt and p-Akt1. High p-Akt1
      expression correlated with lower T stage (P = 0.004), while Akt was not
      associated with any clinicopathologic variables. Kaplan-Meier survival analysis
      revealed that higher expression of Akt, p-Akt1 were respectively correlated with
      favourable prognosis (16.0[4.7-27.3] vs 9.3[9.0-9.6] months, P = 0.007, and
      23.0[12.2-33.8] vs 11.1[7.5-14.7] months, P = 0.004, respectively). Multivariate
      analysis identified p-Akt1 as a significant independent favourable prognostic
      factor (HR=0.421, P = 0.010). CONCLUSIONS: These results suggest that high p-Akt1
      expression may be a favourable prognostic factor in pancreatic cancer.

PMID- 20697674
TI  - Acceptability of medical students by patients from private and public family
      practices and specialist outpatient clinics.
AB  - INTRODUCTION: Previous studies on patient acceptance of medical student teaching
      were from Western populations and in one setting only. However, there has been no
      prospective study comparing patient acceptability before and after an actual
      experience. We studied patient acceptability of medical student teaching in
      private and public family practices and public hospital specialist outpatient
      clinics in Singapore, and before and after an actual medical student teaching
      consultation. MATERIALS AND METHODS: We conducted an anonymous cross-sectional
      survey from March through October 2007 of Singaporean or permanent resident
      patients attending 76 teaching private family practices, 9 teaching public family
      practices and 8 specialty clinics in a teaching public hospital. We used pre
      consultation cross-sectional patient surveys in all three settings. For private
      family practice setting only, post-consultation patient survey was conducted
      after an actual experience with medical student presence. RESULTS: Out of 5123
      patients, 4142 participated in the cross-sectional survey (80.9%) and 1235 of
      1519 patients in the prospective cohort study (81.3%). Eighty percent were
      comfortable with medical students present, 79% being interviewed and 60% being
      examined. Regarding being examined by medical students, parents of children were
      least comfortable while patients between 41 to 60 years were most comfortable
      (adjusted OR = 1.99 [1.55-2.57]). Females were less comfortable with medical
      student teaching than males. Chinese patients were the least comfortable about
      being interviewed or examined by medical students among the ethnic groups.
      Indians were most comfortable with being interviewed by medical students
      (adjusted OR = 1.38 [1.02-1.86]) but Malays were the most comfortable being
      examined by them (adjusted OR = 1.32 [1.07-1.62]). Family practice patients were
      more receptive to medical student teaching than the hospital's specialist
      outpatients. Common barriers to patient acceptance were lack of assurance of
      patient privacy, dignity and confidentiality. Actual exposure to medical student
      teaching did not change levels of patient acceptance. CONCLUSIONS: Compared to
      similar studies from Western countries, Asian patients appear to be less
      receptive to medical student teaching than Western patients. Family practice
      settings offer medical students a more receptive learning environment.

PMID- 20697675
TI  - Complications following tracheoesophageal puncture: a tertiary hospital
      experience.
AB  - INTRODUCTION: In laryngectomised patients, tracheoesophageal speech is the gold
      standard for voice rehabilitation. This study evaluated complications related to
      the tracheoesophageal puncture (TEP) and the success rate in voice prosthesis
      after total laryngectomy at our institution over a 10-year period. MATERIALS AND
      METHODS: A retrospective review of 22 TEPs was performed between January 1998 and
      December 2008. The timing of TEP, type of voice prosthesis, surgical and
      prosthesis-related complications, and TEP closure were noted. RESULTS: Eighteen
      percent of the patients underwent primary and 82% secondary TEP. Our patients
      were predominantly males (95.4%) of Chinese descent with a mean age of 62.1
      years. The types of voice prostheses used were ProvoxTM (n = 15), Voicemasters (n
      = 6), and Blom-Singer (n = 1). Prosthesis- related complications occurred in
      77.3%. Notable complications were leakage (82.5%), prosthesis displacement
      (41.2%), intractable aspiration (29.4%), and aspiration of prosthesis (23.5%).
      The most common surgical-related complication was tracheostomal stenosis. An
      array of interventions comprising resizing or changing prosthesis type,
      nasogastric catheter insertion, stomaplasty, purse string suturing, and
      bronchoscopic removal of bronchial aspirated prosthesis were implemented to
      address encountered complications. In a mean follow-up of 34.8 months, 68.2% of
      patients achieved functional tracheoesophageal speech (75% of primary TEP and 67%
      of secondary TEP). There were 7 TEP closures indicated by persistent leakage,
      recurrent dislodgement, phonatory failure and, in 1 patient, persistent pain.
      CONCLUSIONS: TEP has become an integral part in the rehabilitation of a
      laryngectomee. However, management of the frequent complications related to TEP
      requires specific efforts and specialistic commitments in order to treat them.

PMID- 20697676
TI  - Are new resuscitation guidelines better? Experience of an Asian metropolitan
      hospital.
AB  - INTRODUCTION: Cardiopulmonary resuscitation (CPR) guidelines were revised in 2005
      based on new evidence and expert consensus. However, the benefits of the new
      guidelines remain undetermined and their influence has not been published in
      Asia. This study aimed to evaluate the impact of implementing the new
      resuscitation guidelines and identify factors that influence the discharge
      survival of out-of-hospital cardiac arrest (OHCA) patients in an Asian
      metropolitan city. MATERIALS AND METHODS: This was an observational cohort study
      of all OHCA patients seen by the emergency medical service during the period
      before (Nov 2003 to Oct 2005) and after (May 2006 to Oct 2008) implementing the
      new resuscitation guidelines. Detailed clinical information was recorded using
      the Ustein style template. Statistical analysis was done using X2 test or t-test
      for univariate analysis and the logistic regression model for multivariate
      analysis. RESULTS: There were 463 patients before and 430 patients after the new
      guidelines who received resuscitation. The rate of recovery of spontaneous
      circulation (ROSC), survival-to-intensive care unit (ICU) admission, and survival
      to-hospital discharge all showed no benefits regarding the new resuscitation
      guidelines (ROSC: 42% vs 39%, P = 0.32; Survival-to-ICU admission: 33% vs 30%, P
      = 0.27; survival-to-hospital discharge: 10% vs 7%, P = 0.09). The rate of
      ventricular fibrillation/pulseless ventricular tachycardia (VF/pulseless VT),
      rate of witnessed arrest, and rate of bystander CPR were much lower than in
      Western studies. After multivariate logistic regression, factors related to
      discharge survival were witnessed arrest and initial rhythm with VF/pulseless VT.
      The new resuscitation guidelines did not significantly influence the discharge
      survival. CONCLUSIONS: We did not observe any improvement in survival after
      implementing the new guidelines. Independent factors of survival-to-hospital
      discharge are witnessed arrest and initial rhythm with VF/pulseless VT. Because
      the rates of VF/pulseless VT and bystander CPR in Asia are low, popularising CPR
      training programmes and increasing the rate of bystander CPR may be more
      important for improving OHCA survival rates than frequent guideline changes.

PMID- 20697677
TI  - Enlargement of the right maxilla - report of an unusual peripheral osteoma.

PMID- 20697678
TI  - Bannayan Riley Ruvalcaba syndrome.

PMID- 20697679
TI  - Management of thrombotic thrombocytopenic purpura in metastatic prostate cancer
      with only endocrine therapy.

PMID- 20697680
TI  - Macronodular tuberculosis: imaging resemblance of cholangiocarcinoma.

PMID- 20697681
TI  - Coexistence of unicentric Castleman's Disease and locally advanced papillary
      renal cell carcinoma: More than a coincidental association?

PMID- 20697682
TI  - Unusual pacemaker lead placement in an unsuspecting heart.

PMID- 20697683
TI  - [Experiences from more than 2,100 hernia repair operations. How has the therapy
      changed in the last 15 years?].
AB  - INTRODUCTION: Inguinal hernia (IH) surgery has changed fundamentally during the
      last 25 years due to tension-free repair, minimally-invasive approaches and
      growing influence of economy in medical decision making. Aim of the study was the
      documentation and analysis of changes in IH surgery during the last 15 years in
      our patient cohort. MATERIAL AND METHODS: Patients undergoing elective or
      emergency inguinal/femoral hernia repair from January 1995 to December 2009 were
      included in the study. Analysis of patient data was carried out by prospective
      online recording. RESULTS: A total of 1,908 patients with 2,124 IHs were treated
      in the study period and the number of IH repairs decreased continuously. The
      number of recurrent hernias peaked in 2005-2009 with 16.4%. The average
      preoperative hospital stay decreased from 2.4 to 0.4 days and the postoperative
      hospital stay from 7.0 to 3.3 days. The percentage of suture repairs declined
      from 54.9% in 1995 to 4.1% in 2009 and the percentage of open tension-free
      repairs rose to 52.9% in 1998. In the following years the majority of repairs
      were performed by minimally invasive procedures but in 2009 the percentage of
      conventional hernia repairs exceeded the rate of minimally invasive repairs.
      CONCLUSION: The main reason for these changes is the implementation of diagnosis
      related groups which hampers inpatient repair of "simple" inguinal hernias,
      favors short hospital stay and does not adequately reimburse minimally invasive
      repairs.

PMID- 20697685
TI  - The renin, angiotensin, aldosterone, and obesity connection.

PMID- 20697684
TI  - [Cold-induced urticaria and angioedema. Classification, diagnosis and therapy].
AB  - The onset of wheals and/or angioedema following the exposure to cold may be
      associated with a number of different diseases. Most frequently this occurs in
      cold contact urticaria, a type of physical urticaria, which is characterized by a
      positive cold stimulation test. The clinical symptoms are based on cold-dependent
      mast cell activation with subsequent release of proinflammatory mediators. In
      cases of negative or atypical reaction to cold stimulation testing rare acquired
      atypical or familiar cold urticaria forms may be suspected. Strict avoidance of
      cold should be recommended as far as possible. As the underlying causes of cold
      contact urticaria are widely unknown, the symptomatic use of non-sedating
      antihistamines is the treatment of first choice. The very rare familiar cold auto
      inflammatory syndrome (FCAS) is based on CIAS1/NLRP3 mutations and may be treated
      effectively by neutralization of pathogenic interleukin 1beta.

PMID- 20697686
TI  - Isolation of cancer stem cells from transformed human mesenchymal stem cell line
      F6.
AB  - Cancer stem cells (CSCs) have the characteristics of self-renewal, unlimited
      proliferation, and initiating new tumors. However, the origin of CSCs is still
      controversial. F6, a tumor cell line transformed from human fetal mesenchymal
      stem cells, was established in our previous study. Whether CSCs exist in this
      mutated cell line remains unclear. In the present study, we isolated CSCs from F6
      cells based on CD133 expression using flow cytometry and investigated the
      biological characteristics of CD133+ F6 cells (F6-CD133+). We observed that the
      F6-CD133+ cells grew faster and had a higher capacity of colony formation than
      the F6-CD133- cells and parental F6 cells in vitro. In addition, F6-CD133+ cells
      had a higher tumorigenic ability than F6-CD133- cells in vivo since 1,000 F6
      CD133+ cells were able to form tumors in nude mice. Cell viability assay revealed
      that F6-CD133+ cells were more sensitive to cisplatin while less to 5
      fluorouracil. Furthermore, gene expression profile analysis showed that there
      were 673 differentially expressed genes between F6-CD133+ and F6-CD133- cells,
      many of which were involved in key cell signaling pathways. Taken together, our
      findings confirm that F6 cells contain a population of CSCs that contribute to
      its heterogeneity and tumorigenic potential, indicating that transformed stem
      cells could be the source of CSCs, and targeting this population may lead to more
      effective tumor treatments.

PMID- 20697687
TI  - Using probe genotypes to dissect QTL * environment interactions for grain yield
      components in winter wheat.
AB  - Yield is known to be a complex trait, the expression of which interacts strongly
      with environmental conditions. Understanding the genetic basis of these genotype
      * environment interactions, particularly under limited input levels, is a key
      objective when selecting wheat genotypes adapted to specific environments. Our
      principal objectives were thus: (1) to identify genomic regions [quantitative
      trait loci (QTL)] involving QTL * environment interactions (QEI) and (2) to
      develop a strategy to understand the specificity of these regions to certain
      environments. The two main components of yield were studied: kernel number (KN)
      and thousand-kernel weight (TKW). The Arche * Recital doubled-haploid population
      of 222 lines was grown in replicated field trials during 2000 and 2001 at three
      locations in France, under two nitrogen levels. The 12 environments were
      characterized in terms of water deficit, radiation, temperature and nitrogen
      stress based on measurements conducted on the four-probe genotypes: Arche,
      Recital, Ritmo and Soissons. A four-step strategy was developed to explain QTL
      specificity to some environments: (1) the detection of QTL for KN and TKW in each
      environment; (2) the estimation of genotypic sensitivities as the factorial
      regression slope of KN and TKW to environmental covariates and the detection of
      QTL for these genotypic sensitivities; (3) study of the co-locations of QTL for
      KN and TKW and of the QTL for sensitivities; in the event of a co-location
      partitioning the QEI, appropriate covariates were employed; (4) a description of
      the environments where QTL were detected for KN and TKW using the environmental
      covariates. A total of 131 QTL were found to be associated with KN, TKW and their
      sensitivity to environmental covariates across the 12 environments. Four of these
      QTL, for both KN and TKW, were located on linkage groups 1B, 2D1, 4B and 5A1, and
      displayed pleiotropic effects. Factorial regression explained from 15.1 to 83.2%
      of the QEI for KN and involved three major environmental covariates: cumulative
      radiation-days +/-3 days at meiosis, cumulative degree-days >25 degrees C +/-3
      days at meiosis and nitrogen stress at flowering. For TKW, 13.5-81.8% of the
      effect of the QEI was partitioned and involved three major environmental
      covariates: water deficit from flowering to the milk stage, cumulative degree
      days >0 degrees C from the milk stage to maturity and soil water deficit at
      maturity. A comparative analysis was then performed on the QTL detected during
      this and previous studies published on QEI and some interacting QTL may be common
      to different genetic backgrounds. Focusing on these QTL common to different
      genetic backgrounds would give some guidance to understand genotype * environment
      interaction.

PMID- 20697688
TI  - HbA1c as predictor of all-cause mortality in individuals at high risk of diabetes
      with normal glucose tolerance, identified by screening: a follow-up study of the
      Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen-Detected
      Diabetes in Primary Care (ADDITION), Denmark.
AB  - AIMS/HYPOTHESIS: Stepwise screening for type 2 diabetes will not only identify
      people with the disease or some other form of dysglycaemia (impaired fasting
      glucose or impaired glucose tolerance), but also many individuals who are
      phenotypically at high risk of developing diabetes, but currently have normal
      glucose tolerance (NGT). We therefore sought to assess whether HbA(1c) adds
      prognostic information in relation to all-cause mortality in people who have NGT
      and a high risk of type 2 diabetes mellitus. METHODS: In a Danish population
      based stepwise screening programme for type 2 diabetes mellitus in general
      practice, we identified 15,634 persons at high risk of type 2 diabetes, who had
      NGT and a recorded HbA(1c) measurement. As comparison groups, we included 1,401
      people identified as having type 2 diabetes mellitus and 8,149 individuals
      characterised as being at low risk of diabetes. All individuals were followed
      from time of screening (April 2001 to December 2006) until death or 31 October
      2009. Excess mortality was estimated using Cox proportional hazard models with
      all-cause mortality as the outcome measure. RESULTS: Compared with individuals
      with NGT and HbA(1c) below 6.0%, adjusted hazard ratios were: 1.21 (95% CI 0.95
      1.56) for individuals with NGT and HbA(1c) between 6.0% and 6.5%; 2.48 (95% CI
      1.23-4.99) for individuals with NGT and HbA(1c) 6.5% or above (in this group
      there were eight deaths among 68 individuals); 1.73 (95% CI 1.40-2.13) for
      individuals with type 2 diabetes mellitus. CONCLUSIONS/INTERPRETATION: HbA(1c)
      level in people with NGT and at high risk of diabetes was clearly associated with
      increased all-cause mortality.

PMID- 20697689
TI  - Interleukin-6-deficient mice develop hepatic inflammation and systemic insulin
      resistance.
AB  - AIMS/HYPOTHESIS: The role of IL-6 in the development of obesity and hepatic
      insulin resistance is unclear and still the subject of controversy. We aimed to
      determine whether global deletion of Il6 in mice (Il6 (-/-)) results in standard
      chow-induced and high-fat diet (HFD)-induced obesity, hepatosteatosis,
      inflammation and insulin resistance. METHODS: Male, 8-week-old Il6 (-/-) and
      littermate control mice were fed a standard chow or HFD for 12 weeks and
      phenotyped accordingly. RESULTS: Il6 (-/-) mice displayed obesity,
      hepatosteatosis, liver inflammation and insulin resistance when compared with
      control mice on a standard chow diet. When fed a HFD, the Il6 (-/-) and control
      mice had marked, equivalent gains in body weight, fat mass and ectopic lipid
      deposition in the liver relative to chow-fed animals. Despite this normalisation,
      the greater liver inflammation, damage and insulin resistance observed in chow
      fed Il6 (-/-) mice relative to control persisted when both were fed the HFD.
      Microarray analysis from livers of mice fed a HFD revealed that genes associated
      with oxidative phosphorylation, the electron transport chain and tricarboxylic
      acid cycle were uniformly decreased in Il6 (-/-) relative to control mice. This
      coincided with reduced maximal activity of the mitochondrial enzyme beta
      hydroxyacyl-CoA-dehydrogenase and decreased levels of mitochondrial respiratory
      chain proteins. CONCLUSIONS/INTERPRETATION: Our data suggest that IL-6 deficiency
      exacerbates HFD-induced hepatic insulin resistance and inflammation, a process
      that appears to be related to defects in mitochondrial metabolism.

PMID- 20697690
TI  - Mortality and causes of death of acute and transient psychotic disorders.
AB  - BACKGROUND: Little is known about mortality associated with acute transient
      psychoses. This paper examines mortality and causes of death of ICD-10 F23 'Acute
      and transient psychotic disorders' (ATPD). METHOD: Data from all subjects aged
      over 15 years who were enrolled in 1996 in the Danish psychiatric register with a
      first-admission diagnosis of ATPD were linked to the national register of causes
      of death. The standardized mortality ratio (SMR) for overall mortality and
      specific categories were calculated. RESULTS: Over the period 1996-2001, 87
      (17.3%) of 503 patients with ATPD had died, accounting for a mortality rate of
      35.3 per 1,000 person/years. The SMR for all causes (2.9), natural causes (2.5),
      and unnatural causes (9.2) were significantly increased. Suicide had the greatest
      SMR (30.9). CONCLUSIONS: These findings argue for excess mortality of ATPD
      particularly from suicide.

PMID- 20697691
TI  - Can a clinical test of hamstring strength identify football players at risk of
      hamstring strain?
AB  - PURPOSE: To demonstrate the potential for a simple clinical test of hamstring
      muscle strength to identify susceptibility to muscle strain injury. METHODS: A
      single-case design was used; specifically, an elite-level male Australian Rules
      football player performed bilateral isometric maximum voluntary contractions of
      the hamstring muscles on a weekly basis for a period of 5 weeks preceding a right
      hamstring muscle strain injury. RESULTS: Minimal asymmetry (no greater than +/
      1.2% difference) was evident in the hamstring isometric maximum voluntary
      contractions during the first 4 weeks, but 5 days prior to injury, the right
      hamstring isometric maximum voluntary contraction was reduced by 10.9% compared
      to the left. CONCLUSION: Measuring asymmetry in isometric maximum voluntary
      contractions of the hamstring muscles may be a useful clinical test to identify
      susceptibility to muscle strain injury.

PMID- 20697692
TI  - The in vitro antibiofilm activity of selected marine bacterial culture
      supernatants against Vibrio spp.
AB  - The aim of the work is to investigate the effect of marine bacterial culture
      supernatants on biofilm formation of Vibrio spp., a major menace in aquaculture
      industries. Vibrio spp. biofilm cause life-threatening infections in humans and
      animals. Forty-three marine bacterial culture supernatants were screened against
      the hydrophobicity index, initial attachment and biofilm formation in Vibrio spp.
      Twelve culture supernatants showed antibiofilm activity. The bacterial culture
      supernatants S8-07 (Bacillus pumilus) and S6-01 (B. indicus) inhibited the
      initial attachment, biofilm formation and dispersed the mature biofilm at 5% v/v
      concentration without inhibiting the growth. Analysis by light microscopy and
      confocal laser scanning microscopy showed that the architecture of the biofilm
      was destroyed by bacterial supernatants when compared to the control. The
      bacterial supernatants also reduce the surface hydrophobicity of Vibrio spp.
      which is one of the important requirements for biofilm formation. Further
      characterization of antibiofilm activity in S8-07 culture supernatant confirmed
      that it is an enzymatic activity and the size is more than 10 kDa and in S6-01,
      it is a heat-stable, non-protein compound. Furthermore, both the supernatants
      failed to show any biosurfactant activity. The culture supernatants of S8-07 and
      S6-01 with promising antibiofilm property have potential for application in
      medicine and marine aquaculture.

PMID- 20697693
TI  - Diverse pathways for salicin utilization in Shigella sonnei and Escherichia coli
      carrying an impaired bgl operon.
AB  - Utilization of the aryl-beta-glucosides salicin or arbutin in most wild-type
      strains of E. coli is achieved by a single-step mutational activation of the bgl
      operon. Shigella sonnei, a branch of the diverse E. coli strain tree, requires
      two sequential mutational steps for achieving salicin utilization as the bglB
      gene, encoding the phospho-beta-glucosidase B, harbors an inactivating insertion.
      We show that in a natural isolate of S. sonnei, transcriptional activation of the
      gene SSO1595, encoding a phospho-beta-glucosidase, enables salicin utilization
      with the permease function being provided by the activated bgl operon. SSO1595 is
      absent in most commensal strains of E. coli, but is present in extra-intestinal
      pathogens as bgcA, a component of the bgc operon that enables beta-glucoside
      utilization at low temperature. Salicin utilization in an E. coli bglB laboratory
      strain also requires a two-step activation process leading to expression of BglF,
      the PTS-associated permease encoded by the bgl operon and AscB, the phospho-beta
      glucosidase B encoded by the silent asc operon. BglF function is needed since
      AscF is unable to transport beta-glucosides as it lacks the IIA domain involved
      in phopho-relay. Activation of the asc operon in the Sal(+) mutant is by a
      promoter-up mutation and the activated operon is subject to induction. The
      pathway to achieve salicin utilization is therefore diverse in these two
      evolutionarily related organisms; however, both show cooperation between two
      silent genetic systems to achieve a new metabolic capability under selection.

PMID- 20697694
TI  - Antioxidant pathways are up-regulated during biological nitrogen fixation to
      prevent ROS-induced nitrogenase inhibition in Gluconacetobacter diazotrophicus.
AB  - Gluconacetobacter diazotrophicus, an endophyte isolated from sugarcane, is a
      strict aerobe that fixates N(2). This process is catalyzed by nitrogenase and
      requires copious amounts of ATP. Nitrogenase activity is extremely sensitive to
      inhibition by oxygen and reactive oxygen species (ROS). However, the elevated
      oxidative metabolic rates required to sustain biological nitrogen fixation (BNF)
      may favor an increased production of ROS. Here, we explored this paradox and
      observed that ROS levels are, in fact, decreased in nitrogen-fixing cells due to
      the up-regulation of transcript levels of six ROS-detoxifying genes. A cluster
      analyses based on common expression patterns revealed the existence of a stable
      cluster with 99.8% similarity made up of the genes encoding the alpha-subunit of
      nitrogenase Mo-Fe protein (nifD), superoxide dismutase (sodA) and catalase type E
      (katE). Finally, nitrogenase activity was inhibited in a dose-dependent manner by
      paraquat, a redox cycler that increases cellular ROS levels. Our data revealed
      that ROS can strongly inhibit nitrogenase activity, and G. diazotrophicus alters
      its redox metabolism during BNF by increasing antioxidant transcript levels
      resulting in a lower ROS generation. We suggest that careful controlled ROS
      production during this critical phase is an adaptive mechanism to allow nitrogen
      fixation.

PMID- 20697695
TI  - Evidence from the structure and function of cytochromes c(2) that nonsulfur
      purple bacterial photosynthesis followed the evolution of oxygen respiration.
AB  - Cytochromes c(2) are the nearest bacterial homologs of mitochondrial cytochrome
      c. The sequences of the known cytochromes c(2) can be placed in two subfamilies
      based upon insertions and deletions, one subfamily is most like mitochondrial
      cytochrome c (the small C2s, without significant insertions and deletions), and
      the other, designated large C2, shares 3- and 8-residue insertions as well as a
      single-residue deletion. C2s generally function between cytochrome bc(1) and
      cytochrome oxidase in respiration (ca 80 examples known to date) and between
      cytochrome bc(1) and the reaction center in nonsulfur purple bacterial
      photosynthesis (ca 21 examples). However, members of the large C2 subfamily are
      almost always involved in photosynthesis (12 of 14 examples). In addition, the
      gene for the large C2 (cycA) is associated with those for the photosynthetic
      reaction center (pufBALM). We hypothesize that the insertions in the large C2s,
      which were already functioning in photosynthesis, allowed them to replace the
      membrane-bound tetraheme cytochrome, PufC, that otherwise mediates between the
      small C2 or other redox proteins and photosynthetic reaction centers. Based upon
      our analysis, we propose that the involvement of C2 in nonsulfur purple bacterial
      photosynthesis was a metabolic feature subsequent to the evolution of oxygen
      respiration.

PMID- 20697696
TI  - GABA(A) positive modulator and NMDA antagonist-like discriminative stimulus
      effects of isoflurane vapor in mice.
AB  - RATIONALE: Several neurotransmitter systems have been hypothesized to be involved
      in the in vivo effects of volatile anesthetics. Drug discrimination may represent
      a novel procedure to explore the neurochemical systems underlying the sub
      anesthetic behavioral effects of these compounds. OBJECTIVES: The purpose of the
      present study was to examine the contribution of GABA(A) and NMDA receptors to
      the discriminative stimulus effects of a behaviorally active sub-anesthetic
      concentration of isoflurane vapor. METHODS: Sixteen B6SJLF1/J mice were trained
      to discriminate 10 min of exposure to 6,000 ppm isoflurane vapor from air.
      Substitution tests were conducted with volatile anesthetics, abused vapors,
      GABA(A) positive modulators, NMDA antagonists, and nitrous oxide. RESULTS: The
      volatile anesthetics, enflurane and halothane as well as the abused vapors
      toluene and 1,1,1-trichloroethane fully substituted for isoflurane. The GABA(A)
      positive modulators, pentobarbital, midazolam, and zaleplon but not the direct
      GABA(A) agonist, muscimol, produced high levels of partial substitution for
      isoflurane. The anticonvulsant, valproic acid fully substituted for isoflurane
      but a second, tiagabine, did not substitute. The competitive NMDA antagonist, CGS
      19755, fully and the non-competitive NMDA antagonist, dizocilpine, partially
      substituted for isoflurane. The glycine-site NMDA antagonist, L-701,324 did not
      substitute for isoflurane. Gamma-hydroxybutric acid and nitrous oxide gas also
      failed to substitute for isoflurane. CONCLUSIONS: The discriminative stimulus
      effects of sub-anesthetic concentrations of isoflurane vapor are shared by other
      vapor anesthetics and abused inhalants. The discriminative stimulus effects of
      isoflurane vapor appear to be mediated by both positive allosteric modulation of
      GABA(A) receptors as well as antagonism of NMDA receptors.

PMID- 20697697
TI  - Effects of prazosin, clonidine, and propranolol on the elevations in brain reward
      thresholds and somatic signs associated with nicotine withdrawal in rats.
AB  - RATIONALE: Tobacco withdrawal is characterized by a negative mood state and
      relatively mild somatic symptoms. Increased noradrenergic transmission has been
      reported to play an important role in opioid withdrawal, but little is known
      about the role of noradrenergic transmission in nicotine withdrawal. OBJECTIVES:
      The aim of these experiments was to investigate the effects of prazosin,
      clonidine, and propranolol on the negative mood state and somatic signs
      associated with nicotine withdrawal in rats. METHODS: A discrete-trial
      intracranial self-stimulation procedure was used to assess the negative affective
      state of nicotine withdrawal. Elevations in brain reward thresholds are
      indicative of a deficit in brain reward function. RESULTS: In all the
      experiments, the nicotinic acetylcholine receptor antagonist mecamylamine (3
      mg/kg) elevated the brain reward thresholds of the nicotine-treated rats and did
      not affect those of the control rats. The alpha1-adrenergic receptor antagonist
      prazosin (0.0625 and 0.125 mg/kg) dose-dependently attenuated the elevations in
      brain reward thresholds associated with precipitated nicotine withdrawal. The
      alpha2-adrenergic receptor agonist clonidine (10-40 MUg/kg) and the nonselective
      beta-adrenergic receptor antagonist propranolol (2.5-10 mg/kg) did not attenuate
      the elevations in brain reward thresholds associated with nicotine withdrawal.
      Furthermore, mecamylamine (2 mg/kg) induced more somatic signs in the nicotine
      treated rats than in the control rats. Clonidine and propranolol, but not
      prazosin, decreased the total number of somatic signs associated with nicotine
      withdrawal. CONCLUSION: Blockade of alpha1-adrenergic receptors attenuates the
      deficit in brain reward function associated with nicotine withdrawal. Antagonism
      of beta-adrenergic receptors or stimulation of alpha2-adrenergic receptors
      attenuates the somatic symptoms of nicotine withdrawal.

PMID- 20697698
TI  - Eye-head coordination in the guinea pig II. Responses to self-generated
      (voluntary) head movements.
AB  - Retinal image stability is essential for vision but may be degraded by head
      movements. The vestibulo-ocular reflex (VOR) compensates for passive
      perturbations of head position and is usually assumed to be the major neural
      mechanism for ocular stability. During our recent investigation of vestibular
      reflexes in guinea pigs free to move their heads (Shanidze et al. in Exp Brain
      Res, 2010), we observed compensatory eye movements that could not have been
      initiated either by vestibular or neck proprioceptive reflexes because they
      occurred with zero or negative latency with respect to head movement. These
      movements always occurred in association with self-generated (active) head or
      body movements and thus anticipated a voluntary movement. We found the
      anticipatory responses to differ from those produced by the VOR in two
      significant ways. First, anticipatory responses are characterized by temporal
      synchrony with voluntary head movements (latency approximately 1 versus
      approximately 7 ms for the VOR). Second, the anticipatory responses have higher
      gains (0.80 vs. 0.46 for the VOR) and thus more effectively stabilize the retinal
      image during voluntary head movements. We suggest that anticipatory responses act
      synergistically with the VOR to stabilize retinal images. Furthermore, they are
      independent of actual vestibular sensation since they occur in guinea pigs with
      complete peripheral vestibular lesions. Conceptually, anticipatory responses
      could be produced by a feed-forward neural controller that transforms efferent
      motor commands for head movement into estimates of the sensory consequences of
      those movements.

PMID- 20697699
TI  - Effects of five years of chronic STN stimulation on muscle strength and movement
      speed.
AB  - This study examined the long-term effects of chronic subthalamic nucleus (STN)
      deep brain stimulation (DBS) using both clinical evaluation and laboratory motor
      control measures. Over a 5-year time period, changes in the motor section of the
      Unified Parkinson's Disease Rating Scale (UPDRS) and movement speed and strength
      at the ankle joint were evaluated on and off STN DBS in eight patients with
      Parkinson's disease (PD). Four patients were also studied at the elbow joint.
      Patients with PD originally received unilateral STN DBS between years 2001 and
      2003. They were re-evaluated after 5 years of long-term STN DBS between years
      2006-2008. At baseline (year 0) and after 5 years, patients with PD were tested
      off treatment and on STN DBS. In each testing condition, patients performed
      ballistic, single degree of freedom ankle dorsiflexion and ankle plantarflexion
      movements and peak velocity was calculated. Patients also performed maximal
      voluntary contractions at the ankle joint in both directions, and peak torque was
      calculated. Results showed increased motor UPDRS scores from year 0 to year 5,
      but STN DBS was efficacious in reducing them. In contrast to the increase in
      motor UPDRS scores, motor control results showed a marked improvement in peak
      velocity and peak torque over the 5-year time period in the off treatment
      condition, and STN DBS was efficacious by improving both peak velocity and peak
      torque. The current findings suggest that 5 years of chronic STN DBS can have
      beneficial effects on the motor system over the long term in discrete motor tasks
      in which maximal effort and maximal neural output is required.

PMID- 20697700
TI  - Oxycodone concentrations are greatly increased by the concomitant use of
      ritonavir or lopinavir/ritonavir.
AB  - PURPOSE: this study aimed to investigate the effect of antivirals ritonavir and
      lopinavir/ritonavir on the pharmacokinetics and pharmacodynamics of oral
      oxycodone, a widely used opioid receptor agonist used in the treatment of
      moderate to severe pain. METHODS: a randomized crossover study design with three
      phases at intervals of 4 weeks was conducted in 12 healthy volunteers. Ritonavir
      300 mg, lopinavir/ritonavir 400/100 mg, or placebo b.i.d. for 4 days was given to
      the subjects. On day 3, 10 mg oxycodone hydrochloride was administered orally.
      Plasma concentrations of oxycodone, noroxycodone, oxymorphone, and noroxymorphone
      were determined for 48 h. Pharmacokinetic parameters were calculated with
      standard noncompartmental methods. Behavioral effects and experimental cold pain
      analgesia were assessed for 12 h. ANOVA for repeated measures was used for
      statistical analysis. RESULTS: ritonavir and lopinavir/ritonavir increased the
      area under the plasma concentration-time curve of oral oxycodone by 3.0-fold
      (range 1.9- to 4.3-fold; P <0.001) and 2.6-fold (range 1.9- to 3.3-fold; P
      <0.001). The mean (+/- SD) elimination half-life increased after ritonavir and
      lopinavir/ritonavir from 3.6 +/- 0.6 to 5.6 +/- 0.9 h (P <0.001) and 5.7 +/- 0.9
      h (P <0.001), respectively. Both ritonavir (P <0.001) and lopinavir/ritonavir (P
      <0.05) increased the self-reported drug effect of oxycodone. CONCLUSIONS:
      ritonavir and lopinavir/ritonavir greatly increase the plasma concentrations of
      oral oxycodone in healthy volunteers and enhance its effect. When oxycodone is
      used clinically in patients during ritonavir and lopinavir/ritonavir treatment,
      reductions in oxycodone dose may be needed to avoid opioid-related adverse
      effects.

PMID- 20697702
TI  - X-ray dose from pediatric cardiac catheterization: a comparison of materials and
      methods for measurement or calculation.
AB  - Pediatric cardiac catheterization procedures have the potential to transmit high
      X-ray doses, which may lead to acute effects or latent skin reactions. Direct
      measurement of radiation dose was facilitated using nanodot dosimeters and
      radiochromic film. Direct measurement results were compared with vendor-listed
      dosimetry and calculation using phantom data. Vendor-listed data demonstrated a
      wide discrepancy with measured data, whereas the calculation reproducibly
      overestimated the actual dose. A simple formula was derived to calculate the dose
      using fluoroscopy time, cine frame quantity and average cine mA in a biplane
      environment.

PMID- 20697701
TI  - Accelerated evolutionary rate of housekeeping genes in tunicates.
AB  - Phylogenomics has recently revealed that tunicates represent the sister-group of
      vertebrates in the newly defined clade Olfactores. However, phylogenomic and
      comparative genomic studies have also suggested that tunicates are characterized
      by an elevated rate of molecular evolution and a high degree of genomic
      divergence. Despite the recurrent interest in the group, the picture of tunicate
      peculiar evolutionary dynamics is still fragmentary, as it mainly lies in studies
      focusing on only a few model species. In order to expand the available genomic
      data for the group, we used the high-throughput 454 technology to sequence the
      partial transcriptome of a previously unsampled tunicate, Microcosmus squamiger.
      This allowed us to get further insights into tunicate-accelerated evolution
      through a comparative analysis based on pertinent phylogenetic markers, i.e., a
      core of 35 housekeeping genes conserved across bilaterians. Our results showed
      that tunicates evolved on average about two times faster than the other
      chordates, yet the degree of this acceleration varied extensively upon genes and
      upon lineages. Appendicularia and Aplousobranchia were detected as the most
      divergent groups which were also characterized by highly heterogeneous
      substitution rates across genes. Finally, an estimation of the d (N)/d (S) ratio
      in three pairs of closely related taxa within Olfactores did not reveal strong
      differences between the tunicate and vertebrate lineages suggesting that for this
      set of housekeeping genes, the accelerated evolution of tunicates is plausibly
      due to an elevated mutation rate rather than to particular selective effects.

PMID- 20697703
TI  - Giant aortic arch aneurysm after interrupted aortic arch repair.
AB  - An 8-year-old boy developed a large aneurysm of the aortic arch after neonatal
      complete repair of interrupted aortic arch type B and closure of a perimembranous
      ventricular septal defect. To our knowledge, this unusual complication has not
      been previously reported in the English literature.

PMID- 20697704
TI  - Right ventricular function in children with bronchial asthma: a tissue Doppler
      echocardiographic study.
AB  - Asthma is the most common cause of respiratory disability among children.
      Patients with severe bronchial asthma can experience cor pulmonale later in life,
      but little is known about the function of the right ventricle early in the
      disease. This study aimed to investigate the right ventricular function in
      children with bronchial asthma as detected by tissue Doppler echocardiography.
      This case-control study compared 60 asthmatic children ages 5 to 15 years between
      attacks (study group) with 60 apparently healthy children (control group). All
      the children were subjected to full history-taking, complete physical
      examination, measurement of peak expiratory flow rate (PEFR), chest x-ray,
      electrocardiography (ECG), echocardiographic examination, and both conventional
      and tissue Doppler study. The results of the tissue Doppler study examining the
      right ventricular diastolic function showed that peak E' velocity (10.08 +/- 2.8
      cm/s), peak A' velocity (5.7 +/- 2.5 cm/s), E'/A' ratio (1.77 +/- 0.58 m/s), and
      isovolumetric relaxation time (IVRT) of the lateral tricuspid annulus (138.9 +/-
      30.7 m/s) among the asthmatic patients differed significantly from those among
      the control subjects (12.4 +/- 2.3, 7.8 +/- 2.1 cm/s; 1.58 +/- 0.32, and 91.1 +/-
      32.6 m/s, respectively). In addition, the E' velocity and IVRT of the lateral
      tricuspid annulus were significantly different among the mild, moderate, and
      severe cases (P < 0.001). It is concluded that although the clinical and
      conventional echocardiographic findings of the asthmatic children were apparently
      normal, the tissue Doppler echocardiographic study showed right ventricular
      dysfunction that is positively correlated with the severity of asthma. These
      findings signify the diagnostic value of tissue Doppler echocardiography for the
      early detection and monitoring of such deleterious effects among asthmatic
      patients.

PMID- 20697705
TI  - Fungal propagules and DNA in feces of two detritus-feeding amphipods.
AB  - Aquatic shredders (leaf-eating invertebrates) preferentially ingest and digest
      leaves colonized by aquatic hyphomycetes (fungi). This activity destroys leaf
      associated fungal biomass and detritial resources in streams. Fungal counter
      adaptations may include the ability to survive passage through the invertebrate's
      digestive tract. When fecal pellets of Gammarus tigrinus and Hyalella azteca were
      incubated with sterile leaves, spores of nine (G. tigrinus) and seven (H. azteca)
      aquatic hyphomycete species were subsequently released from the leaves,
      indicating the presence of viable fungal structures in the feces. Extraction,
      amplification, and sequencing of DNA from feces revealed numerous fungal
      phylotypes, two of which could be assigned unequivocally to an aquatic
      hyphomycete. The estimated contributions of major fungal groups varied depending
      on whether 18S or ITS sequences were amplified and cloned. We conclude that a
      variable proportion of fungal DNA in the feces of detritivores may originate from
      aquatic hyphomycetes. Amplified DNA may be associated with metabolically active,
      dormant, or dead fungal cells.

PMID- 20697706
TI  - Biotechnological processes for biodiesel production using alternative oils.
AB  - As biodiesel (fatty acid methyl ester (FAME)) is mainly produced from edible
      vegetable oils, crop soils are used for its production, increasing deforestation
      and producing a fuel more expensive than diesel. The use of waste lipids such as
      waste frying oils, waste fats, and soapstock has been proposed as low-cost
      alternative feedstocks. Non-edible oils such as jatropha, pongamia, and rubber
      seed oil are also economically attractive. In addition, microalgae, bacteria,
      yeast, and fungi with 20% or higher lipid content are oleaginous microorganisms
      known as single cell oil and have been proposed as feedstocks for FAME
      production. Alternative feedstocks are characterized by their elevated acid value
      due to the high level of free fatty acid (FFA) content, causing undesirable
      saponification reactions when an alkaline catalyst is used in the
      transesterification reaction. The production of soap consumes the conventional
      catalyst, diminishing FAME production yield and simultaneously preventing the
      effective separation of the produced FAME from the glycerin phase. These problems
      could be solved using biological catalysts, such as lipases or whole-cell
      catalysts, avoiding soap production as the FFAs are esterified to FAME. In
      addition, by-product glycerol can be easily recovered, and the purification of
      FAME is simplified using biological catalysts.

PMID- 20697707
TI  - Lessons from the genomes of extremely acidophilic bacteria and archaea with
      special emphasis on bioleaching microorganisms.
AB  - This mini-review describes the current status of recent genome sequencing
      projects of extremely acidophilic microorganisms and highlights the most current
      scientific advances emerging from their analysis. There are now at least 56 draft
      or completely sequenced genomes of acidophiles including 30 bacteria and 26
      archaea. There are also complete sequences for 38 plasmids, 29 viruses, and
      additional DNA sequence information of acidic environments is available from
      eight metagenomic projects. A special focus is provided on the genomics of
      acidophiles from industrial bioleaching operations. It is shown how this initial
      information provides a rich intellectual resource for microbiologists that has
      potential to open innovative and efficient research avenues. Examples presented
      illustrate the use of genomic information to construct preliminary models of
      metabolism of individual microorganisms. Most importantly, access to multiple
      genomes allows the prediction of metabolic and genetic interactions between
      members of the bioleaching microbial community (ecophysiology) and the
      investigation of major evolutionary trends that shape genome architecture and
      evolution. Despite these promising beginnings, a major conclusion is that the
      genome projects help focus attention on the tremendous effort still required to
      understand the biological principles that support life in extremely acidic
      environments, including those that might allow engineers to take appropriate
      action designed to improve the efficiency and rate of bioleaching and to protect
      the environment.

PMID- 20697708
TI  - Magnetic resonance imaging of intramuscular metastases.
AB  - OBJECTIVE: The aim of the present study was to analyse magnetic resonance
      findings of intramuscular metastases (IM) in a relatively large series. MATERIALS
      AND METHODS: From January 2000 to January 2010, 28 patients (207 metastases) were
      retrospectively identified in the radiological database of the Martin-Luther
      University. Several different scanning protocols were used depending on the
      localisation of IM. In 12 patients diffusion-weighted (DW) images were obtained
      with a multi-shot SE-EPI sequence. Apparent diffusion coefficient (ADC) maps were
      also calculated. Furthermore, fusion images were manually generated between the
      DW and half-Fourier acquisition single-shot turbo spin echo (HASTE) images.
      RESULTS: On T2-weighted images, 97% of the recognised IM were hyperintense in
      comparison to unaffected musculature, and 3% were mixed iso- to hyperintense. On
      T1-weighted images most IM (91%) were homogeneously isointense in comparison to
      muscle tissue, whereas 4% were hypointense, and 5% lightly hyperintense. ADC maps
      were calculated for 91 metastases ranging from 0.99 to 4.00 mm(2)s(-1) (mean
      value 1.99 +/- 0.66). ADC values of low (<1.5) signal intensity (SI) were
      identified in 26%, moderate SI (from 1.5 to 3.0) in 68%, and high SI (>3.0) in
      6%. Of the IM that were investigated with contrast medium, 88.5% showed marked
      enhancement. It was homogeneous in 88% and heterogenous in 6%. Rim enhancement
      with central low attenuation was seen in 6%. There was no difference in
      enhancement characteristics with respect to ADC values or fusion patterns.
      Peritumoral enhancement was identified in 2.4%. CONCLUSION: Magnetic resonance
      features of muscle metastases are relatively typical and consist of round or oval
      intramuscular masses with well-defined margins, marked enhancement, low or
      moderate ADC values, and moderate to high signal intensity on fusion images.

PMID- 20697709
TI  - A large posttraumatic subclavian artery aneurysm complicated by artery occlusion
      and arteriobronchial fistula successfully treated using a covered stent.
AB  - The treatment of posttraumatic aneurysms of peripheral arteries using covered
      stents is increasingly commonplace. We present the case of a 10-year-old girl
      with a pseudoaneurysm of the subclavian artery complicated by an arteriobronchial
      fistula with hemorrhaging into the bronchial tree and distal subclavian artery
      occlusion. Despite the lack of artery patency, endovascular stent graft
      implantation was successful. Pseudoaneurysm exclusion and involution was
      achieved, together with a patent implant and maintained collateral circulation
      patency.

PMID- 20697710
TI  - Vascular components of the posterior mediastinum: applications for video-assisted
      thoracoscopic surgery.
AB  - PURPOSE: This study introduced an anatomical basis for thoracoscope-assisted
      thoracolumbar spinal anterior approach. METHODS: This work was carried out in
      terms of 29 corpse specimens anatomizing and the CT three-dimensional images of
      25 normal adults observing. RESULTS: The observation by the thoracolumbar spine
      side of the adult corpse specimens showed that the segmental arteries and veins
      constantly existed and ran in the central supersulcus of the corresponding
      vertebral body's side; the segmental artery had several branches; the zone
      between the upper and lower segmental arteries formed a relative non-vascular
      nerve safe zone, where the intervertebral space(disc) located. And the
      observation of the three-dimensional CT image indicated that the segmental
      arteries were visible and ran in the central supersulcus of the corresponding
      vertebral body's side, while the branches were invisible. Besides, the
      arrangement and distribution of the segmental arteries on the three-dimensional
      CT images and the result were basically consistent with that on corpse specimens.
      CONCLUSIONS: The safe zone, with the intervertebral disc as the reference mark,
      could provide enough operation space for surgeries such as thoracoscope-assisted
      anterior interbody fusion and reduce damage to blood vessels as well as surgical
      complications.

PMID- 20697711
TI  - Mandibular nerve entrapment in the infratemporal fossa.
AB  - The posterior trunk of the mandibular nerve (V(3)) comprises of three main
      branches. Various anatomic structures may entrap and potentially compress the
      mandibular nerve branches. A usual position of mandibular nerve (MN) compression
      is the infratemporal fossa (ITF) which is one of the most difficult regions of
      the skull base to access surgically. The anatomical positions of compression are:
      the incomplete or complete ossified pterygospinous (LPs) or pterygoalar (LPa)
      ligament, the large lamina of the lateral plate of the pterygoid process and the
      medial fibres of the lower belly of the lateral pterygoid (LPt). A contraction of
      the LPt, due to the connection between nerve and anatomic structures (soft and
      hard tissues), might lead to MN compression. Any variations of the course of the
      MN branches can be of practical significance to surgeons and neurologists who are
      dealing with this region, because of possibly significant complications. The
      entrapment of the MN motor branches can lead to paresis or weakness in the
      innervated muscle. Compression of the sensory branches can provoke neuralgia or
      paraesthesia. Lingual nerve (LN) compression causes numbness, hypoesthesia or
      even anaesthesia of the mucous of the tongue, anaesthesia and loss of taste in
      the anterior two-thirds of the tongue, anaesthesia of the lingual gums, as well
      as pain related to speech articulation disorders. Dentists should be very
      suspicious of possible signs of neurovascular compression in the region of the
      ITF.

PMID- 20697712
TI  - A multicenter phase I trial of metronomic oral vinorelbine plus cisplatin in
      patients with NSCLC.
AB  - The purpose of the present study was to determine the maximum-tolerated doses
      (MTDs) and the dose-limiting toxicities of a metronomic administration of oral
      vinorelbine and cisplatin in patients with advanced/metastatic NSCLC. Twenty-six
      patients with advanced/metastatic NSCLC were enrolled. Escalating doses of
      vinorelbine (40-70 mg p.o./trice per week) and cisplatin (70-85 mg/m(2)
      intravenous infusion) were administered on day 1 every 3 weeks. MUTauDs were
      reached at 60 mg thrice/week p.o. for vinorelbine and 85 mg/m(2) for cisplatin.
      Grade 4 neutropenia, febrile neutropenia and grade 4 diarrhea were the dose
      limiting events during the first cycle of chemotherapy. The most common grade III
      IV hematologic toxicity was neutropenia occurring in seven (27%) patients, while
      non-hematological toxicities were relatively infrequent and mostly of grade I or
      II. Objective responses were observed in 20.8% of patients with measurable
      disease. The regimen of metronomic administration and cisplatin is feasible and
      active in patients with NSCLC.

PMID- 20697713
TI  - A comparative study of pharmacokinetics, urinary excretion and tissue
      distribution of platinum in rats following a single-dose oral administration of
      two platinum(IV) complexes LA-12 (OC-6-43)-bis(acetato)(1
      adamantylamine)amminedichloroplatinum(IV) and satraplatin (OC-6-43)
      bis(acetato)amminedichloro(cyclohexylamine)platinum(IV).
AB  - PURPOSE: This study compared the pharmacokinetics, tissue distribution, and
      urinary excretion of platinum in rats after single oral doses of LA-12 and
      satraplatin. METHODS: Both platinum derivatives were administered to male Wistar
      rats as suspensions in methylcellulose at four equimolar doses within the range
      of 37.5-300 mg LA-12/kg body weight. Blood sampling was performed until 72 h, and
      plasma and plasma ultrafiltrate were separated. Moreover, urine was collected
      until 72 h, and kidney and liver tissue samples were obtained at several times
      after administration. Platinum was measured by atomic absorption spectrometry.
      The pharmacokinetics of platinum was analyzed by population modelling and post
      hoc Bayesian estimation as well as using non-compartmental pharmacokinetic
      analysis of the mean concentration-time curves. RESULTS: Platinum was detected in
      all plasma and ultrafiltrate samples 15 min after oral administration of both
      compounds and peaked between 3-4 h and 1-3 h, respectively. Similar for LA-12 and
      satraplatin, the C (max) and AUC values of plasma and ultrafiltrate platinum
      increased less than in proportion to dose. The mean C (max) and AUC values of
      plasma platinum observed after administration of LA-12 were from 0.84 to 2.5 mg/l
      and from 20.2 to 75.9 mg h/l. For ultrafiltrate platinum, the corresponding
      ranges were 0.16-0.78 mg/l and 0.63-1.8 mg h/l, respectively. The AUC of plasma
      platinum was higher after satraplatin (P < 0.001). However, administration of LA
      12 resulted in significantly higher AUC values of ultrafiltrate platinum after
      the doses of 150 mg and 300 mg/kg (P < 0.01), respectively, and the C (max)
      values were significantly higher starting from the dose of 75 mg/kg LA-12 and
      upward (P < 0.01). Cumulative 72-h urinary recovery of platinum dose was below 5%
      for both compounds, and it decreased with the dose of satraplatin (P < 0.01),
      while a numerical decrease was observed after administration of LA-12 that did
      not reach statistical significance (P = 0.41). The renal clearance of free
      platinum was similar regardless of the dose and compound administered. Platinum
      concentrations in the liver homogenate exceeded those in the kidney. Distribution
      of platinum to tissues was higher after LA-12 compared to satraplatin. The
      difference in kidney platinum increased with dose and was twofold after 350 mg/kg
      LA-12. Liver platinum was twofold higher after LA-12 across all four doses.
      CONCLUSIONS: In conclusion, this first comparative pharmacokinetic study with LA
      12 and satraplatin shows that characteristics of platinum exposure evaluated in
      the plasma, plasma ultrafiltrate and kidney and liver tissues increase less than
      in proportion to dose following a single-dose administration of 37.5-300 mg/kg to
      Wistar rats. These findings together with the dose-related elevation in the
      pharmacokinetic characteristics V/F and CL/F of platinum and ultrafiltrate
      platinum as well as a drop in platinum urinary recovery are consistent with a
      dose-related decrease in the extent of oral bioavailability most likely due to
      saturable intestinal absorption.

PMID- 20697714
TI  - Prevalence of Stx phages in environments of a pig farm and lysogenic infection of
      the field E. coli O157 isolates with a recombinant converting Phage.
AB  - The prevalence and nature of Shiga toxin (Stx)-producing Escherichia coli (STEC)
      and Stx phage were investigated in 720 swine fecal samples randomly collected
      from a commercial breeding pig farm in China over a 1-year surveillance period.
      Eight STEC O157 (1.1%), 33 STEC non-O157 (4.6%), and two stx-negative O157 (0.3%)
      isolates were identified. Fecal filtrates were screened directly for Stx phages
      using E. coli K-12 derivative strains MC1061 as indicator, yielding 15 Stx1 and
      57 Stx2 phages. One Stx1 and eight Stx2 phages were obtained following
      norfloxacin induction of the eight field STEC O157 isolates. All Stx1 phages had
      hexagonal heads with long tails, while Stx2 phages had three different
      morphologies. Notably, most of field STEC O157 isolates released more free phages
      and Stx toxin after induction with ciprofloxacin. Furthermore, upon infection
      with the recombinant phage PhiMin27(Deltastx::cat), E. coli laboratory strains
      produced both lysogenic and lytic phage, whereas two of the eight O157 STEC
      isolates produced only lysogens. The lysogens from laboratory strains produced
      infectious particles similar to PhiMin27. Similarly, the lysogens from the STEC
      O157 isolates released Stx phage too, although free PhiMin27(Deltastx::cat)
      particles were not detected. Collectively, our results reveal that breeding pig
      farms could be important reservoirs for Stx phages and that residual
      antibacterial agents may enhance the release of Stx phages and the expression of
      Stx.

PMID- 20697715
TI  - Field evidence for the potential of Rhodobacter capsulatus as Biofertilizer for
      flooded rice.
AB  - In a previous study, we evaluated the effects of inoculating rice plants with the
      phototrophic purple nonsulfur bacterium Rhodobacter capsulatus (Rc) on growth and
      yield of rice in pots and lysimeter experiments and the results obtained have
      been highly encouraging. In this study, we carried out two field experiments: one
      in the experimental farm of the Faculty of Agriculture, Fayoum University, and
      the second in a farmer's field in Kafr El-sheikh, to assess the effects of Rc on
      growth and yield of rice in comparison and in combination with chemical nitrogen
      fertilizer (CNF) and farmyard manure. The results indicated that both biological
      and grain yields in all the Rc inoculated treatments were significantly higher
      than those in the uninoculated corresponding treatments in both fields. With
      regard to grain yield, the major factor for determining the effectiveness of any
      agricultural treatment, inoculation with Rc in combination with 50% of the
      recommended CNF rate gave a grain yield that was statistically equivalent to that
      obtained with 100% of the recommended CNF rate. These results provide a clear
      evidence for the potential of Rc as biofertilizer for flooded rice under field
      conditions.

PMID- 20697716
TI  - TORC1 kinase and the S-phase cyclin Clb5 collaborate to promote mitotic spindle
      assembly and DNA replication in S. cerevisiae.
AB  - The Target of Rapamycin complex 1 (TORC1) is a central regulator of eukaryotic
      cell growth that is inhibited by the drug rapamycin. In the budding yeast
      Saccharomyces cerevisiae, translational defects associated with TORC1
      inactivation inhibit cell cycle progression at an early stage in G1, but little
      is known about the possible roles for TORC1 later in the cell cycle. We
      investigated the rapamycin-hypersensitivity phenotype of cells lacking the S
      phase cyclin Clb5 (clb5Delta) as a basis for uncovering novel connections between
      TORC1 and the cell cycle regulatory machinery. Dosage suppression experiments
      suggested that the clb5Delta rapamycin hypersensitivity reflects a unique Clb5
      associated cyclin-dependent kinase (CDK) function that cannot be performed by
      mitotic cyclins and that also involves motor proteins, particularly the kinesin
      like protein Kip3. Synchronized cell experiments revealed rapamycin-induced
      defects in pre-anaphase spindle assembly and S phase progression that were more
      severe in clb5Delta than in wild-type cells but no apparent activation of Rad53
      dependent checkpoint pathways. Some rapamycin-treated cells had aberrant spindle
      morphologies, but rapamycin did not cause gross defects in the microtubule
      cytoskeleton. We propose a model in which TORC1 and Clb5/CDK act coordinately to
      promote both spindle assembly via a pathway involving Kip3 and S phase
      progression.

PMID- 20697717
TI  - Current trends and future prospects of biotechnological interventions through
      tissue culture in apple.
AB  - Apple (Malus domestica Borkh.), which is a widely cultivated, important economic
      fruit crop with nutritive and medicinal importance, has emerged as a model
      horticultural crop in this post-genomic era. Apple cultivation is heavily
      dependent on climatic condition and is susceptible to several diseases caused by
      fungi, bacteria, viruses, insects, etc. Extensive research work has been carried
      out to standardize tissue culture protocols and utilize them in apple
      improvement. We review the in vitro shoot multiplication, rooting, transformation
      and regeneration methodologies in apple and tabulate various such protocols for
      easy reference. The utility and limitation of transgenesis in apple improvement
      have also been summarized. The concepts of marker-free plants, use of non
      antibiotic resistance selectable markers, and cisgenic and intragenic approaches
      are highlighted. Furthermore, the limitations, current trends and future
      prospects of tissue culture-mediated biotechnological interventions in apple
      improvement are discussed.

PMID- 20697718
TI  - Ehlers-Danlos syndrome and neurological features: a review.
AB  - Ehlers-Danlos Syndrome is a term that comprises a variety of inherited connective
      tissue disorders characterized primarily by skin hyperextensibility, joints
      hypermobility and excessive dislocations, easy bruisability, generalized
      fragility. If much is known about orthopedic or physiatric features of this
      syndrome, poor is known about the neurological ones. Thus neurological assessment
      is very important due to the possible various clinical manifestations in this
      syndrome.

PMID- 20697719
TI  - Orbitozygomatic resection for hypothalamic hamartoma and epilepsy: patient
      selection and outcome.
AB  - PURPOSE: This study aims to examine the outcomes of ten patients after
      orbitozygomatic (OZ) pterional surgery in cases of refractory epilepsy caused by
      hypothalamic hamartomas (HH). METHODS: Ten patients with HH and treatment
      resistant epilepsy (mean age 18.3 years, range 0.7 to 42.7) underwent HH
      resection with an OZ approach (n = 8) or an OZ approach combined with a
      transventricular endoscopic approach (n = 2). Follow-up for the patients ranged
      from 0.5 to 6.2 years (mean 3.1). Outcomes were prospectively monitored with the
      use of a proprietary database. RESULTS: Four patients (40%) are seizure-free, and
      four (40%) have had greater than 50% reduction in seizures. One patient had no
      significant change in seizure frequency, and one patient died unexpectedly 2.8
      years after surgery. Six patients had total or near-total HH resection (98-100%
      of HH lesion volume). Of these, four of six (66%) were seizure-free, and two had
      at least greater than 50% reduction in seizures. Residual complications include
      diabetes insipidus (n = 1), poikilothermia (n = 1), visual field deficit (n = 1),
      and hemiparesis (n = 1). Eight families (80%) reported improved quality of life.
      CONCLUSIONS: Patients with treatment-resistant epilepsy and tumors with an
      inferior or horizontal plane of attachment to the hypothalamus should continue to
      be approached from below. Those with both intrahypothalamic and parahypothalamic
      components may require approaches from above and below, either simultaneously or
      staged. For appropriately selected patients, the success of controlling seizures
      with an OZ is comparable to results utilizing transcallosal or transventricular
      approaches. The likelihood of controlling seizures appears to correlate with
      extent of resection.

PMID- 20697720
TI  - Syringomyelia secondary to shunt malfunction.

PMID- 20697721
TI  - Update on pediatric extracranial vascular anomalies of the head and neck.
AB  - PURPOSE: Vascular anomalies most frequently present at birth or in early
      childhood, and the craniofacial region is the most common site of involvement. A
      long history of misleading nomenclature born of confusion about the presentation
      and natural history of various vascular anomalies has made appropriate diagnosis
      difficult. The present article emphasizes the importance of clarity of
      nomenclature for proper diagnosis, both clinically and radiographically, to guide
      appropriate therapy. In addition, updates on clinical concepts, imaging, and
      treatment strategies will be discussed. Pediatric vascular anomalies can be
      divided into two broad categories: vascular tumors and vascular malformations.
      This biologic classification is based on differences in natural history, cellular
      turnover, and histology. An updated classification was introduced in 1996 by the
      International Society for the Study of Vascular Anomalies (ISSVA) to include
      infantile hemangioma variants, other benign vascular tumors, and combined
      lesions. Widespread confusion propagated throughout the literature and in
      clinical practice stems from the continued improper use of many of the terms used
      to describe vascular tumors and malformations ignoring their pathophysiology.
      This leads to errors in diagnosis and the dissemination of misinformation to
      patients and clinicians. Certain terms should be abandoned for more appropriate
      terms. The clinical presentation usually identifies what general type of vascular
      anomaly is present, either vascular tumor or vascular malformation. Imaging
      provides crucial information about the initial diagnosis and aids in follow-up.
      CONCLUSIONS: Adoption and use of uniform nomenclature in the ISSVA classification
      system is the first vital step in correct diagnosis and treatment of often
      complicated vascular tumors and vascular malformations. A multidisciplinary team
      approach is necessary to provide optimal care for patients, and the necessity for
      specialists in all areas to communicate using standardized terminology cannot be
      overemphasized.

PMID- 20697722
TI  - Risk factors for morbidity and mortality after single-layer continuous suture for
      ileocolonic anastomosis.
AB  - AIM: The study was designed to determine the suitability of a single-layer
      continuous anastomosis for ileo-colonic anastomoses and to determine
      perioperative risk factors for morbidity and mortality in a teaching hospital.
      PATIENTS AND METHODS: Perioperative data of 463 patients undergoing colonic
      surgery with an ileocolonic anastomosis between 2000 and 2007 were
      retrospectively reviewed. Outcomes were compared using univariate and
      multivariate analyses to identify risk factors for morbidity, including
      anastomotic leakage, and mortality. RESULTS: The overall anastomotic leakage rate
      was 2.1%. In more than 50% right hemicolectomies were performed for colonic
      cancer. Univariate analysis showed a significant association of the underlying
      diagnosis with the leakage rate (ischemia 3.0% vs. carcinoma 1.3%). Multivariate
      analysis identified age, ASA score, diagnosis, and urgency as risk factors for
      morbidity; and an urgent operation setting (vital indications), a body mass index
      >25, diabetes mellitus, and a hypotensive circulation upon admission as
      predictors of anastomotic leakage. The mortality rate was 20% (2/10) among
      patients with anastomotic leakage and 2.9% (13/453) in those without anastomotic
      leakage. CONCLUSION: Single-layer continuous anastomoses for ileo-colonic surgery
      can be safely performed, even in a teaching setting. Four preoperative risk
      factors for morbidity and four different factors for anastomotic leakage could be
      identified in multivariate analysis. If feasible, these factors should have an
      impact on the preoperative decision-making progress.

PMID- 20697723
TI  - Is dietary fat associated with the risk of colorectal cancer? A meta-analysis of
      13 prospective cohort studies.
AB  - BACKGROUND: The results of animal studies suggest there is a significant role for
      dietary fat in the development of colorectal cancer (CRC). However, inconsistent
      results have been reported by epidemiological studies. AIM OF STUDY: To evaluate
      the association between total dietary fat and risk of colorectal cancer
      development using a meta-analysis based on prospective cohort studies. METHODS:
      Published literature was retrieved from Medline, Embase and CNKI (China Knowledge
      Resource Integrated Database) databases updated to 1st May, 2009. Overall,
      thirteen prospective cohort studies with 3,635 cases and 459,910 participants
      were included. RESULTS: The combined relative risk (RR) [95% confidence interval
      (95%CI)] for the risk of CRC was 0.99 (0.89,1.09) when the highest level of total
      dietary fat was versus (vs.) the lowest level. Stratified analyses according to
      gender, ethnicity, country and age showed that the highest level of total dietary
      fat did not increase the risk of CRC [RR (95%CI): 0.89 (0.77,1.03) for males;
      1.09 (0.94,1.26) for females; 1.08 (0.94,1.25) for Caucasians; 0.90 (0.77,1.04)
      for Asians; 1.13 (0.94,1.36) for Americans; 0.92 (0.81,1.04) for individuals
      older than 40]. Besides those, the highest level of total fat diet also did not
      increase the risk of neither colon cancer [RR (95%CI): 0.96 (0.82,1.13)] nor
      rectal cancer [RR (95%CI):1.07 (0.63,1.82)]. Furthermore, neither animal fat nor
      plant fat were associated with the risk of CRC [RR (95%CI): 1.05 (0.91-1.22) for
      animal fat and 0.96 (0.82-1.11) for plant fat]. CONCLUSIONS: This meta-analysis
      suggests that dietary fat may not be associated with the increased risk of CRC.
      More well-designed studies with larger population performed among Asians are
      needed to further evaluate the associations. In addition, probable bias caused by
      measurement error should be noticed in this meta-analysis, and measurement error
      needs to be adjusted in the future studies.

PMID- 20697724
TI  - Pharmacologic reversal of neurogenic and neuroplastic abnormalities and cognitive
      impairments without affecting Abeta and tau pathologies in 3xTg-AD mice.
AB  - In addition to the occurrence of numerous neurofibrillary tangles and Abeta
      plaques, neurogenesis and neuronal plasticity are markedly altered in Alzheimer
      disease (AD). Although the most popular therapeutic approach has been to inhibit
      neurodegeneration, another is to promote neurogenesis and neuronal plasticity by
      utilizing the regenerative capacity of the brain. Here we show that, in a
      transgenic mouse model of AD, 3xTg-AD mice, there was a marked deficit in
      neurogenesis and neuroplasticity, which occurred before the formation of any
      neurofibrillary tangles or Abeta plaques and was associated with cognitive
      impairment. Furthermore, peripheral administration of Peptide 6, an 11-mer, which
      makes an active region of ciliary neurotrophic factor (CNTF, amino acid residues
      146-156), restored cognition by enhancing neurogenesis and neuronal plasticity in
      these mice. Although this treatment had no detectable effect on Abeta and tau
      pathologies in 9-month animals, it enhanced neurogenesis in dentate gyrus,
      reduced ectopic birth in the granular cell layer, and increased neuronal
      plasticity in the hippocampus and cerebral cortex. These findings, for the first
      time, demonstrate the possibility of therapeutic treatment of AD and related
      disorders by peripheral administration of a peptide corresponding to a
      biologically active region of CNTF.

PMID- 20697726
TI  - Sesamol inhibits UVB-induced ROS generation and subsequent oxidative damage in
      cultured human skin dermal fibroblasts.
AB  - The exposure of cells to ultraviolet B radiation (UVB) can induce the production
      of reactive oxygen species (ROS) which damage cellular components. Free radical
      scavengers and antioxidants can interfere with the production of ROS. We studied
      cytotoxicity, intracellular ROS levels, lipid peroxidation, antioxidant status
      and oxidative DNA damage in cultured human skin dermal fibroblast adult cells
      (HDFa) exposed to UVB in the presence of sesamol, a natural phenolic compound.
      The levels of cytotoxicity, intracellular ROS, lipid peroxidation, oxidative DNA
      damage and apoptotic morphological changes were significantly increased in UVB
      irradiated HDFa cells. We also observed that the activities of enzymatic
      antioxidants (superoxide dismutase, catalase and glutathione peroxidase) and the
      levels of non-enzymatic antioxidant status (GSH) were significantly decreased in
      UVB irradiated cells. On the other hand, sesamol pretreatment significantly
      decreased cytotoxicity, intracellular ROS, lipid peroxidation, oxidative DNA
      damage and apoptotic morphological changes in sesamol-pretreated and UVB
      irradiated HDFa cells. We have also observed increased enzymatic and non
      enzymatic antioxidants status in sesamol plus UVB-irradiated cells. Among the
      different doses tested, 80 MUM of sesamol shows maximum protection for UVB
      induced oxidative damage. In conclusion, UVB-induced ROS formation, cell
      fatality, lipid peroxidation, antioxidant depletion and oxidative DNA damage in
      HDFa cells is inhibited by sesamol, which, probably through its ROS scavenging
      activity.

PMID- 20697725
TI  - Protease-activated receptor-2 mediates the expression of inflammatory cytokines,
      antimicrobial peptides, and matrix metalloproteinases in keratinocytes in
      response to Propionibacterium acnes.
AB  - Propionibacterium acnes (P. acnes) has been known to produce various exogenous
      proteases, however, their role in acne pathogenesis remains largely unknown.
      Proteases elicit cellular responses, at least in part, via proteinase-activated
      receptor-2 (PAR-2), which is known to mediate inflammation and immune response.
      In this study, we investigated whether proteases from P. acnes could activate PAR
      2 on keratinocytes and induce pro-inflammatory cytokines, antimicrobial peptides
      (AMPs), and matrix metalloproteinases (MMPs) via PAR-2 signaling. We examined PAR
      2 expression and protease activity in acne lesions using immunofluorescence
      staining and in situ zymography. The effect of the culture supernatant of P.
      acnes on Ca(2+) signaling in immortalized keratinocytes (HaCaT) was measured
      using a fluorescence method. HaCaT cells were treated with P. acnes strain ATCC
      6919 culture supernatant, with or without pretreatment with serine protease
      inhibitor or selective PAR-2 antagonist and the gene expression of pro
      inflammatory cytokines, AMPs, and MMPs was detected using real-time reverse
      transcription-polymerase chain reaction. We found that the protease activity and
      PAR-2 expression were increased in acne lesions. The P. acnes culture supernatant
      induced calcium signaling in keratinocytes via PAR-2 and stimulated the mRNA
      expression of interleukin (IL)-1alpha, -8, tumor necrosis factor (TNF)-alpha,
      human beta defensin (hBD)-2, LL-37, MMP-1, -2, -3, -9, and -13 in keratinocytes,
      which was significantly inhibited by serine protease inhibitor as well as
      selective PAR-2 specific antagonist. These results indicate that PAR-2 plays an
      important role in the pathogenesis of acne by inducing inflammatory mediators in
      response to proteases secreted from P. acnes.

PMID- 20697727
TI  - The usage and discontinuation of contraceptive methods.
AB  - OBJECTIVE: This study aims to determine the rates of contraceptive
      discontinuation and usage failure and to examine their relation with termination
      of pregnancy. MATERIALS AND METHODS: This is a descriptive (cross-sectional) type
      of study. The study population was chosen among women treated at a state hospital
      in Karaman City, located in the southern part of Turkey. A total of 695 women
      were interviewed for the present study. Data were collected using a face-to-face
      interview technique with the questionnaire developed by the researchers. Chi
      square test was applied as the significance test. RESULTS: While 44.3% and 23.7%
      of the women used medical and traditional methods of contraception, respectively,
      32.0% did not use any method at all. Sixty percentage of the unintended
      pregnancies were terminated. Unintended pregnancy rate due to use of the
      withdrawal method was significantly high (p < 0.000). For the reasons of women's
      discontinuation of family planning methods, it was observed that both usage
      failure and unintended pregnancy were among the top reasons for the
      discontinuation of medical methods; discontinuation of the withdrawal method was
      due to unintended pregnancies. CONCLUSIONS: Withdrawal users have the highest
      unintended pregnancy rates. Most of these unintended/unplanned pregnancies are
      terminated. To increase the rate of use of medical contraceptive methods, users
      should be provided with adequate and high-quality consultancy services and
      evaluation of the applicant should be in accordance with the WHO criteria.

PMID- 20697729
TI  - Morphologic and functional glaucomatous change after occurrence of single or
      recurrent optic disc hemorrhages.

PMID- 20697730
TI  - Reproducibility of ocular response analyzer measurements and their correlation
      with central corneal thickness.
AB  - BACKGROUND: To evaluate the inter- and intraobserver variability of ocular
      response analyzer (ORA) measurements, namely corneal-compensated intraocular
      pressure (IOPcc), corneal resistance factor (CRF) and corneal hysteresis (CH).
      METHODS: One randomly chosen eye of 46 healthy volunteers was included in this
      study. Three clinical observers performed three consecutive measurements using
      ORA, with an interval of 1-2 minutes between measurements. In all subjects,
      central corneal thickness (CCT) was measured. The inter- and intraobserver
      reproducibility for IOPcc, CRF and CH was assessed by ANOVA-based intraclass
      correlation coefficient (ICC) and coefficient of variation (CV). RESULTS: The
      mean ICC for interobserver reproducibility was 0.94 for IOPcc, 0.90 for CRF, and
      0.86 for CH. The corresponding CV values were 12.8%, 10.3%, and 13.6%
      respectively. The intraobserver ICC values for IOPcc were 0.86 for the first
      examiner, 0.84 for the second, and 0.89 for the third. CV was 11.7%, 11.9%, and
      11.0% respectively. For CRF, the intraobserver ICC values were 0.69, 0.81, and
      0.63, and corresponding CV values were 9.6%, 8.1, and 10.8%. The intraobserver
      ICC for CH was 0.66 for the first observer, 0.71 for the second, and 0.61 for the
      third examiner. The respective CV values were 12.7%, 11.8%, and 13.9%. There was
      a significant correlation between CCT and CRF (Rsq = 0.13, p = 0.02). The
      correlations of CCT with IOPcc and CH were not significant (p > 0.05).
      CONCLUSIONS: The interobserver reproducibility of ORA measurements was almost
      perfect for IOPcc, CRF, and CH. The intraobserver short-term reproducibility was
      almost perfect for IOPcc and substantial for CRF and CH, for all observers. The
      significant correlation between CCT and CRF, and no association between IOPcc and
      CCT, are in agreement with previous studies. There was no significant correlation
      between CH and CCT in our study. This device might be useful in glaucoma
      diagnosis and management.

PMID- 20697731
TI  - Utility analysis of disability caused by amblyopia and/or strabismus in a
      population-based, historic cohort.
AB  - BACKGROUND: Amblyopia (prevalence 3.4%) is in principle treatable, but
      approximately one quarter of children do not reach reading acuity in the
      amblyopic eye. Adults with persistent amblyopia and/or strabismus experience a
      decrease in quality of life. This was now quantified by patient-perceived utility
      values. METHODS: Subjects were born 1962-1972 and had been treated by occlusion
      therapy for amblyopia by one orthoptist 30-35 years ago. All children in
      Waterland with amblyopia and/or strabismus had been referred to this orthoptist.
      Utilities were derived by methods of time trade-off, TTO (lifetime traded against
      perfect vision) and standard gamble, SG (death risk accepted for perfect vision).
      Most troubling eye disorder (low acuity of the amblyopic eye, lacking stereopsis
      or strabismus) was chosen and ranked among nine chronic disorders according to
      the subject's perceived severity. RESULTS: From 201 patients that could be
      contacted 35 years after occlusion therapy--out of 471 who had been occluded--135
      were included: 17 could not be reached, 34 refused, and 15 had other reasons to
      not participate. Mean age was 40.86 years; 53% were male. Seventy percent were
      willing to trade lifetime according to the TTO method; its mean (log) utility was
      0.963, i.e., a decrease in quality of life of 3.7%. Thirty-seven percent accepted
      death risk according to the SG method; its mean utility was 0.9996. TTO outcomes
      correlated with current near and distance visual acuity. Low acuity of the
      amblyopic eye, chosen as most troubling eye disorder, ranked slightly less severe
      than tooth decay. CONCLUSION: Amblyopia and/or strabismus patients had a slightly
      decreased utility. The decrease is small but still important in the cost
      effectiveness of vision screening because these conditions occur very frequently.

PMID- 20697732
TI  - Cytoplasmic relocation of Daxx induced by Ro52 and FLASH.
AB  - The RING-finger protein Ro52/TRIM21 is known to be an autoantigen and is
      recognized by anti-Ro/SSA antibodies, which are commonly found in patients with
      Sjogren's syndrome and systemic lupus erythematosus. We recently showed that Ro52
      is an E3 ubiquitin ligase and localizes to cytoplasmic bodies that are highly
      motile along the microtubule network. To expand our knowledge of Ro52, we
      searched partners co-operating with Ro52. We performed a yeast two-hybrid
      screening of a human brain cDNA library with Ro52 as bait. This screening
      identified several genes encoding Ro52-interacting proteins, including the
      apoptosis-related proteins, Daxx and FLASH. Further yeast two-hybrid assays
      revealed that Daxx binds to the B30.2 domain of Ro52 and that FLASH binds to
      coiled-coil domains of Ro52 through its death-effector domain-recruiting domain.
      These results suggest that Ro52, Daxx, and FLASH form heteromeric protein
      complexes. Indeed, this was supported by results of immunoprecipitation
      experiments in which we found that Daxx is co-immunoprecipitated with Ro52 in the
      presence of overexpressed FLASH. Importantly, our fluorescence microscopy
      revealed that, although Daxx is predominantly located in the nucleus,
      overexpression of both Ro52 and FLASH leads to relocation of Daxx into the
      cytoplasm. Thus, Ro52 seems to co-operate with FLASH to induce cytoplasmic
      localization of Daxx in cells.

PMID- 20697733
TI  - Work stress, worries, and pain interact synergistically with modelled traffic
      noise on cross-sectional associations with self-reported sleep problems.
AB  - OBJECTIVES: To examine the risk of sleep problems associated with work stress
      (job strain, job demands, and decision authority), worries and pain and to
      investigate the synergistic interaction between these factors and traffic noise.
      METHODS: Sleep problems and predictor variables were assessed in a cross
      sectional public health survey with 12,093 respondents. Traffic noise levels were
      assessed using modelled A-weighted energy equivalent traffic sound levels at the
      residence. The risk of sleep problems was modelled using multiple logistic
      regression analysis. RESULTS: With regard to sleep problems not attributed to any
      external source (general sleep problems), independent main effects were found for
      traffic noise (women), decision authority (women), job strain, job demands,
      suffering from pain or other afflictions, worries about losing the job,
      experiencing bullying at work, having troubles paying the bills, and having a
      sick, disabled, or old relative to take care of (women). Significant synergistic
      effects were found for traffic noise and experiencing bullying at work in women.
      With regard to sleep problems attributed to traffic noise, strong synergistic
      interactions were found between traffic noise and, respectively, job demands
      (men), having pain or other afflictions, taking care of a sick, old, or disabled
      relative, and having troubles paying the bills. Main effects were found for
      worries about losing the job, experiencing bullying at work, job strain (men),
      and decision authority (men). Synergistic interactions could potentially
      contribute with 10-20% of the sleep problems attributed to traffic noise in the
      population. CONCLUSIONS: Work stress, pain, and different worries were
      independently associated with general sleep problems and showed in general no
      synergistic interaction with traffic noise. In contrast, synergistic effects
      between traffic noise and psychological factors were found with regard to sleep
      problems attributed to traffic noise. The synergy may contribute significantly to
      sleep problems attributed to traffic noise in the population.

PMID- 20697734
TI  - Modeling discrete and rhythmic movements through motor primitives: a review.
AB  - Rhythmic and discrete movements are frequently considered separately in motor
      control, probably because different techniques are commonly used to study and
      model them. Yet the increasing interest in finding a comprehensive model for
      movement generation requires bridging the different perspectives arising from the
      study of those two types of movements. In this article, we consider discrete and
      rhythmic movements within the framework of motor primitives, i.e., of modular
      generation of movements. In this way we hope to gain an insight into the
      functional relationships between discrete and rhythmic movements and thus into a
      suitable representation for both of them. Within this framework we can define
      four possible categories of modeling for discrete and rhythmic movements
      depending on the required command signals and on the spinal processes involved in
      the generation of the movements. These categories are first discussed in terms of
      biological concepts such as force fields and central pattern generators and then
      illustrated by several mathematical models based on dynamical system theory. A
      discussion on the plausibility of theses models concludes the work.

PMID- 20697735
TI  - Endothelial nitric oxide synthase transgenic models of endothelial dysfunction.
AB  - Endothelial production of nitric oxide is critical to the regulation of vascular
      responses, including vascular tone and regional blood flow, leukocyte-endothelial
      interactions, platelet adhesion and aggregation, and vascular smooth muscle cell
      proliferation. A relative deficiency in the amount of bioavailable vascular NO
      results in endothelial dysfunction, with conditions that are conducive to the
      development of atherosclerosis: thrombosis, inflammation, neointimal
      proliferation, and vasoconstriction. This review focuses on mouse models of
      endothelial dysfunction caused by direct genetic modification of the endothelial
      nitric oxide synthase (eNOS) gene. We first describe the cardiovascular
      phenotypes of eNOS knockout mice, which are a model of total eNOS gene deficiency
      and thus the ultimate model of endothelial dysfunction. We then describe S1177A
      and S1177D eNOS mutant mice as mouse models with altered eNOS phosphorylation and
      therefore varying degrees of endothelial dysfunction. These include transgenic
      mice that carry the eNOS S1177A and S1177D transgenes, as well as knockin mice in
      which the endogenous eNOS gene has been mutated to carry the S1177A and S1177D
      mutations. Together, eNOS knockout mice and eNOS S1177 mutant mice are useful
      tools to study the effects of total genetic deficiency of eNOS as well as varying
      degrees of endothelial dysfunction caused by eNOS S1177 phosphorylation.

PMID- 20697736
TI  - Changes in contractile properties of skinned single rat soleus and diaphragm
      fibres after chronic hypoxia.
AB  - Hypoxia may be one of the factors underlying muscle dysfunction during ageing and
      chronic lung and heart failure. Here we tested the hypothesis that chronic
      hypoxia per se affects contractile properties of single fibres of the soleus and
      diaphragm muscle. To do this, the force-velocity relationship, rate of force
      redevelopment and calcium sensitivity of single skinned fibres from normoxic rats
      and rats exposed to 4 weeks of hypobaric hypoxia (410 mmHg) were investigated.
      The reduction in maximal force (P(0)) after hypoxia (p=0.031) was more pronounced
      in type IIa than type I fibres and was mainly attributable to a reduction in
      fibre cross-sectional area (p=0.044). In type IIa fibres this was aggravated by a
      reduction in specific tension (p=0.001). The maximal velocity of shortening (V
      (max)) and shape of the force velocity relation (a/P(0)), however, did not differ
      between normoxic and hypoxic muscle fibres and the reduction in maximal power of
      hypoxic fibres (p=0.012) was mainly due to a reduction in P(0). In conclusion,
      chronic hypoxia causes muscle fibre dysfunction which is not only due to a loss
      of muscle mass, but also to a diminished force generating capacity of the
      remaining contractile material. These effects are similar in the soleus and
      diaphragm muscle, but more pronounced in type IIa than I fibres.

PMID- 20697738
TI  - CLE14/CLE20 peptides may interact with CLAVATA2/CORYNE receptor-like kinases to
      irreversibly inhibit cell division in the root meristem of Arabidopsis.
AB  - Towards an understanding of the interacting nature of the CLAVATA (CLV) complex,
      we predicted the 3D structures of CLV3/ESR-related (CLE) peptides and the
      ectodomain of their potential receptor proteins/kinases, and docking models of
      these molecules. The results show that the ectodomain of CLV1 can form homodimers
      and that the 12-/13-amino-acid CLV3 peptide fits into the binding clefts of the
      CLV1 dimers. Our results also demonstrate that the receptor domain of CORYNE
      (CRN), a recently identified receptor-like kinase, binds tightly to the
      ectodomain of CLV2, and this likely leads to an increased possibility for docking
      with CLV1. Furthermore, our docking models reveal that two CRN-CLV2 ectodomain
      heterodimers are able to form a tetramer receptor complex. Peptides of CLV3,
      CLE14, CLE19, and CLE20 are also able to bind a potential CLV2-CRN heterodimer or
      heterotetramer complex. Using a cell-division reporter line, we found that
      synthetic 12-amino-acid CLE14 and CLE20 peptides inhibit, irreversibly, root
      growth by reducing cell division rates in the root apical meristem, resulting in
      a short-root phenotype. Intriguingly, we observed that exogenous application of
      cytokinin can partially rescue the short-root phenotype induced by over
      expression of either CLE14 or CLE20 in planta. However, cytokinin treatment does
      not rescue the short-root phenotype caused by exogenous application of the
      synthetic CLE14/CLE20 peptides, suggesting a requirement for a condition provided
      only in living plants. These results therefore imply that the CLE14/CLE20
      peptides may act through the CLV2-CRN receptor kinase, and that their
      availabilities and/or abundances may be affected by cytokinin activity in planta.

PMID- 20697737
TI  - PIRL1 and PIRL9, encoding members of a novel plant-specific family of leucine
      rich repeat proteins, are essential for differentiation of microspores into
      pollen.
AB  - Plant intracellular Ras-group-related leucine-rich repeat proteins (PIRLs) are a
      plant-specific class of leucine-rich repeat (LRR) proteins related to animal and
      fungal LRRs that take part in developmental signaling and gene regulation. As
      part of a systematic functional study of the Arabidopsis thaliana PIRL gene
      family, T-DNA knockout mutants defective in the closely related PIRL1 and PIRL9
      genes were identified and characterized. Pirl1 and pirl9 single mutants displayed
      normal transmission and did not exhibit an obvious developmental phenotype. To
      investigate the possibility of functional redundancy, crosses to generate double
      mutants were carried out; however, pirl1;pirl9 plants were not recovered.
      Reciprocal crosses between wild type and pirl1/PIRL1;pirl9 plants, which produce
      50% pirl1;pirl9 gametophytes, indicated male-specific transmission failure of the
      double-mutant allele combination. Scanning electron microscopy and viability
      staining showed that approximately half of the pollen produced by
      pirl1/PIRL1;pirl9 plants was inviable and severely malformed. Tetrad analyses
      with qrt1 indicated that pollen defects segregated with the double-mutant allele
      combination, thus demonstrating that PIRL1 and PIRL9 function after meiosis.
      Pollen development was characterized with bright field, fluorescence, and
      transmission electron microscopy. Pirl1;pirl9 mutants stopped growing as
      microspores, failed to initiate vacuolar fission, aborted, and underwent
      cytoplasmic degeneration. Development consistently arrested at the late
      microspore stage, just prior to pollen mitosis I. Thus, PIRL1 and PIRL9 have
      redundant roles essential at a key transition point early in pollen development.
      Together, these results define a functional context for these two members of this
      distinct class of plant LRR genes.

PMID- 20697739
TI  - Ectopic expression of an EAR motif deletion mutant of SlERF3 enhances tolerance
      to salt stress and Ralstonia solanacearum in tomato.
AB  - Ethylene-responsive transcription factors (ERFs) bind specifically to cis-acting
      DNA regulatory elements such as GCC boxes and play an important role in the
      regulation of defense- and stress-related genes in plants. In contrast to other
      ERFs, class II ERFs contain an ERF-associated amphiphilic repression (EAR) domain
      and act as GCC-mediated transcriptional repressors. In this study, SlERF3, a
      class II ERF was isolated from tomato and characterized. To examine whether the
      EAR motif of class II ERF proteins participates in ERF-mediated functions in
      plants, the EAR domain was deleted to generate SlERF3DeltaRD. We show that
      SlERF3DeltaRD protein retains the character of a transcription factor and becomes
      a GCC-mediated transcriptional activator. Constitutive expression of full-length
      SlERF3 in tomato severely suppressed growth and, as a result, no transgenic
      plants were obtained. However, no apparent effects on growth and development of
      SlERF3DeltaRD transgenic plants were observed. Overexpression of SlERF3DeltaRD in
      transgenic tomato induced expression of pathogenesis-related protein genes such
      as PR1, PR2 and PR5, and enhanced tolerance to Ralstonia solanacearum.
      Furthermore, transgenic Arabidopsis and tomatoes constitutively expressing
      SlERF3DeltaRD exhibited reduced levels of membrane lipid peroxidation and
      enhanced tolerance to salt stress. In comparison with wild-type plants grown
      under stress conditions, transgenic SlERF3DeltaRD tomatoes produced more flowers,
      fruits, and seeds. This study illustrates a gene-enhancing tolerance to both
      biotic and abiotic stresses in transgenic plants with the deletion of a repressor
      domain. Our findings suggest that class II ERF proteins may find important use in
      crop improvement or genetic engineering to increase stress tolerance in plants.

PMID- 20697740
TI  - Self-referencing optrodes for measuring spatially resolved, real-time metabolic
      oxygen flux in plant systems.
AB  - The ability to non-invasively measure metabolic oxygen flux is a very important
      tool for physiologists interested in a variety of questions ranging from basic
      metabolism, growth/development, and stress adaptation. Technologies for measuring
      oxygen concentration near the surface of cells/tissues include electrochemical
      and optical techniques. A wealth of knowledge was gained using these tools for
      quantifying real-time physiology. Fiber-optic microprobes (optrodes) have
      recently been developed for measuring oxygen in a variety of biomedical and
      environmental applications. We have adopted the use of these optical microsensors
      for plant physiology applications, and used the microsensors in an advanced
      sensing modality known as self-referencing. Self-referencing is a non-invasive
      microsensor technique used for measuring real-time flux of analytes. This paper
      demonstrates the use of optical microsensors for non-invasively measuring
      rhizosphere oxygen flux associated with respiration in plant roots, as well as
      boundary layer oxygen flux in phytoplankton mats. Highly sensitive/selective
      optrodes had little to no hysteresis/calibration drift during experimentation,
      and an extremely high signal-to-noise ratio. We have used this new tool to
      compare various aspects of rhizosphere oxygen flux for roots of Glycine max, Zea
      mays, and Phaseolus vulgaris, and also mapped developmentally relevant profiles
      and distinct temporal patterns. We also characterized real-time respiratory
      patterns during inhibition of cytochrome and alternative oxidase pathways via
      pharmacology. Boundary layer oxygen flux was also measured for a phytoplankton
      mat during dark:light cycling and exposure to pharamacological inhibitors. This
      highly sensitive technology enables non-invasive study of oxygen transport in
      plant systems under physiologically relevant conditions.

PMID- 20697742
TI  - The long-term outcome after severe trauma of children in Flanders (Belgium): a
      population-based cohort study using the International Classification of
      Functioning--related outcome score.
AB  - Important long-term health problems have been described after severe paediatric
      trauma. The International Classification of Functioning (ICF) was developed as a
      universal framework to describe that health. We evaluated outcome in children
      after 'severe' trauma (defined as: hospitalised >48 h) by means of a
      questionnaire based on this ICF construct (IROS). Questionnaires were sent to
      children; one year after this trauma and to 'control' children without any
      previous 'severe' trauma. We created propensity score-matched pairs (n = 133) and
      evaluated differences in health perception. IROS characteristics were
      investigated by means of Item Response Theory models. We then estimated the
      health state of each individual based on his/her response pattern (factor score
      z01) and investigated the effect of selected covariates with simple linear
      regression. Significant odds ratios for differences between matched groups (p <
      0.05) were observed for among others emotional problems, mobility, societal life
      and family burden, but not for chronic pain. Children in the trauma group showed,
      e.g. significant more physician (estimated relative risk R' 1.7) and psychologist
      (R' 3.5) visits. IROS primarily provides information from medium to high health
      burden levels and factor scores ranged from 0.41 (lowest) to 0.967 (highest
      burden). A significant impact on health burden could only be proven for the
      'state at discharge' (p = 0.015), although there was a tendency towards worse
      factor scores for children that were older, had a higher Injury Severity Score or
      after traffic injury. In conclusion, we showed that the burden of health problems
      for children and families after severe trauma is still high and physical, as well
      as psychosocial in nature. The health state at discharge seems to predict long
      term outcome, which might be of importance in view of, e.g. trajectory
      assistance. IROS may provide an improved scoring system to evaluate outcome after
      (paediatric) injury or critical illness.

PMID- 20697741
TI  - Human immunodeficiency virus type-1 group M quasispecies evolution: diversity and
      divergence in patients co-infected with active tuberculosis.
AB  - The evolution of intra-host human immunodeficiency virus type 1 (HIV-1)
      quasispecies prior and after treating active tuberculosis (TB) with chemotherapy
      in HIV-1/TB patients was assessed. Two time points HIV-1 quasispecies were
      evaluated by comparing HIV-1-infected patients with active tuberculosis (HIV
      1/TB) and HIV-1-infected patients without tuberculosis (HIV-1/non-TB). Plasma
      samples were obtained from the Frankfurt HIV cohort, and HIV-1 RNA was isolated.
      C2V5 env was amplified by PCR and molecular cloning was performed. Eight to
      twenty-five clones were sequenced from each patient. Various phylogenetic
      analyses were performed. We found a significant increase in diversity and
      divergence in HIV-1/TB compared to the HIV-1/non-TB. For HIV-1/TB, the average
      rate of evolution of C2V5 env was higher than previous reports (2.4 * 10(-4)
      substitution/site/day). Two groups of HIV-1/TB were observed based on the rate of
      HIV-1 evolution and coreceptor usage: A fast evolving R5-tropic dominating group
      and a relatively slowly evolving X4 group. The results demonstrated that active
      TB has an impact on HIV-1 viral diversity and divergence over time. The influence
      of active TB on longitudinal evolution of HIV-1 may be predominant for R5
      viruses.

PMID- 20697743
TI  - Antler development and coupled osteoporosis in the skeleton of red deer Cervus
      elaphus: expression dynamics for regulatory and effector genes.
AB  - Antlers of deer display the fastest and most robust bone development in the
      animal kingdom. Deposition of the minerals in the cartilage preceding
      ossification is a specific feature of the developing antler. We have cloned 28
      genes which are upregulated in the cartilaginous section (called mineralized
      cartilage) of the developing ("velvet") antler of red deer stags, compared to
      their levels in the fetal cartilage. Fifteen of these genes were further
      characterized by their expression pattern along the tissue zones (i.e., antler
      mesenchyme, precartilage, cartilage, bone), and by in situ hybridization of the
      gene activities at the cellular level. Expression dynamics of genes col1A1,
      col1A2, col3A1, ibsp, mgp, sparc, runx2, and osteocalcin were monitored and
      compared in the ossified part of the velvet antler and in the skeleton (in ribs
      and vertebrae). Expression levels of these genes in the ossified part of the
      velvet antler exceeded the skeletal levels 10-30-fold or more. Gene expression
      and comparative sequence analyses of cDNAs and the cognate 5' cis-regulatory
      regions in deer, cattle, and human suggested that the genes runx2 and osx have a
      master regulatory role. GC-MS metabolite analyses of glucose, phosphate,
      ethanolamine-phosphate, and hydroxyproline utilizations confirmed the high
      activity of mineralization genes in governing the flow of the minerals from the
      skeleton to the antler bone. Gene expression patterns and quantitative metabolite
      data for the robust bone development in the antler are discussed in an integrated
      manner. We also discuss the potential implication of our findings on the deer
      genes in human osteoporosis research.

PMID- 20697744
TI  - Age at onset in Huntington's disease is modified by the autophagy pathway:
      implication of the V471A polymorphism in Atg7.
AB  - Huntington's disease (HD) is caused by an expansion of a polyglutamine repeat of
      more than 35 units in the huntingtin protein. The expanded repeat length is
      inversely correlated with the age at onset (AAO); however, additional genetic
      factors apart from the expanded CAG repeat length can modify the course and the
      AAO in HD. Aberrations in macroautophagy have been observed in Huntington,
      Alzheimer, Parkinson, motor neuron and prion diseases. Therefore, we hypothesized
      that polymorphisms in autophagy-related (Atg) genes might contribute to the
      variation in the AAO. We initially tested eight single nucleotide polymorphisms
      in five Atg genes (Atg3, Atg5, Atg7, Atg16L1 and Beclin-1) for their frequency of
      >=1%. Subsequently, we investigated the polymorphisms Atg7 V471A and Atg16L1
      T281A for a disease-modifying effect in more than 900 European HD patients
      (including 2 populations consisting of 346 German patients and 327 patients of
      Italian descent). One polymorphism in the Atg7 gene that substitutes alanine for
      valine (V471A) showed a significant effect on the AAO (P=0.0050) and was
      associated with an earlier disease onset of 4 years. Our results further support
      the important pathophysiological role of autophagy in HD.

PMID- 20697745
TI  - Frugivory on Persea lingue in temperate Chilean forests: interactions between
      fruit availability and habitat fragmentation across multiple spatial scales.
AB  - Habitat degradation and fragmentation are expected to reduce seed dispersal rates
      by reducing fruit availability as well as the movement and abundance of
      frugivores. These deleterious impacts may also interact with each other at
      different spatial scales, leading to nonlinear effects of fruit abundance on seed
      dispersal. In this study we assessed whether the degradation and fragmentation of
      southern Chilean forests had the potential to restrict seed dispersal the lingue
      (Persea lingue) tree, a fleshy-fruited tree species. Of five frugivore bird
      species, the austral thrush (Turdus falcklandii) and the fire-eyed diucon (Xolmis
      pyrope) were the only legitimate seed dispersers as well as being the most
      abundant species visiting lingue trees. The results showed little or no direct
      effect of habitat fragmentation on seed dispersal estimates, possibly because the
      assemblage of frugivore birds was comprised habitat-generalist species. Instead,
      the number of fruits removed per focal tree exhibited an enhanced response to
      crop size, but only in the more connected fragments. In the fruit-richer fragment
      networks, there was an increased fragment-size effect on the proportion of fruits
      removed in comparison to fruit-poor networks in which the fragment size effect
      was spurious. We suggest that such nonlinear effects are widespread in fragmented
      forest regions, resulting from the link between the spatial scales over which
      frugivores sample resources and the spatial heterogeneity in fruiting resources
      caused by habitat fragmentation and degradation.

PMID- 20697746
TI  - Radiotherapy-induced nausea and vomiting (RINV): MASCC/ESMO guideline for
      antiemetics in radiotherapy: update 2009.
AB  - Radiation-induced nausea and vomiting (RINV) are still often underestimated by
      radiation oncologists. However, as many as 50-80% of patients undergoing
      radiotherapy (RT) will experience nausea and/or vomiting, depending on the site
      of irradiation. Fractionated RT may involve up to 40 fractions over a 6-8-week
      period, and prolonged symptoms of nausea and vomiting affect quality of life.
      Furthermore, uncontrolled nausea and vomiting may result in patients delaying or
      refusing further radiotherapy. Incidence and severity of nausea and vomiting
      depend on RT-related factors (irradiated site, single and total dose,
      fractionation, irradiated volume, radiotherapy techniques) and patient-related
      factors (gender, general health of the patient, age, concurrent or recent
      chemotherapy, psychological state, tumor stage). The new proposed guideline from
      the Multinational Association of Supportive Care in Cancer and European Society
      of Clinical Oncology summarises the updated data from the literature and takes
      into consideration the existing guidelines. According to the irradiated area (the
      most frequently studied risk factor), the proposed guideline divided these areas
      into four levels of emetogenic risk: high, moderate, low and minimal. In fact,
      the emetogenicity of radiotherapy regimens and recommendations for the
      appropriate use of antiemetics including 5-hydroxytryptamine receptor antagonists
      and steroids are given in regard to the applied radiotherapy or radiochemotherapy
      regimen. This updated guideline offers guidance to the treating physicians for
      effective antiemetic therapies in RINV.

PMID- 20697747
TI  - Real-time tissue elastography as a tool for the noninvasive assessment of liver
      stiffness in patients with chronic hepatitis C.
AB  - BACKGROUND: Although histopathological examination by "invasive" liver biopsy
      remains the gold standard for evaluating disease progression in chronic liver
      disease, noninvasive tools have appeared and have led to great progress in
      diagnosing the stage of hepatic fibrosis. The aim of this study was to assess the
      value of real-time tissue elastography, using an instrument made in Japan, for
      the visible measurement of liver elasticity; in particular, comparing the results
      with those of transient elastography (Fibroscan). METHODS: Real-time tissue
      elastography (RTE), transient elastography (Fibroscan), liver biopsy, and routine
      laboratory analyses were performed in 101 patients with chronic hepatitis C. The
      values for tissue elasticity obtained using novel software (Elasto_ver 1.5.1)
      connected to RTE were transferred to four image features, Mean, Standard
      Deviation (SD), Area, and Complexity. Their association with the stage of
      fibrosis at biopsy and with liver stiffness (kPa) obtained by Fibroscan was
      analyzed. RESULTS: Colored images obtained by RTE were classified into diffuse
      soft, intermediate, and patchy hard patterns and the calculated elasticity
      differed significantly between patients according to and correlated with the
      stages of fibrosis (p < 0.0001). Mean, SD, Area, and Complexity showed
      significant differences between the stages of fibrosis (Tukey-Kramer test, p <
      0.05). In discriminating patients with cirrhosis, the areas under the receiver
      operating characteristic curves (AUC) were 0.91 for Mean, 0.84 for SD, 0.91 for
      Area, 0.93 for Complexity, and 0.95 for Fibroscan. CONCLUSIONS: RTE is a
      noninvasive instrument for the colored visualization of liver elasticity in
      patients with chronic liver disease.

PMID- 20697748
TI  - Agroecology: the key role of arbuscular mycorrhizas in ecosystem services.
AB  - The beneficial effects of arbuscular mycorrhizal (AM) fungi on plant performance
      and soil health are essential for the sustainable management of agricultural
      ecosystems. Nevertheless, since the 'first green revolution', less attention has
      been given to beneficial soil microorganisms in general and to AM fungi in
      particular. Human society benefits from a multitude of resources and processes
      from natural and managed ecosystems, to which AM make a crucial contribution.
      These resources and processes, which are called ecosystem services, include
      products like food and processes like nutrient transfer. Many people have been
      under the illusion that these ecosystem services are free, invulnerable and
      infinitely available; taken for granted as public benefits, they lack a formal
      market and are traditionally absent from society's balance sheet. In 1997, a team
      of researchers from the USA, Argentina and the Netherlands put an average price
      tag of US $33 trillion a year on these fundamental ecosystem services. The
      present review highlights the key role that the AM symbiosis can play as an
      ecosystem service provider to guarantee plant productivity and quality in
      emerging systems of sustainable agriculture. The appropriate management of
      ecosystem services rendered by AM will impact on natural resource conservation
      and utilisation with an obvious net gain for human society.

PMID- 20697749
TI  - Simultaneous ossification of the posterior longitudinal ligament and ossification
      of the ligamentum flavum causing upper thoracic myelopathy in DISH: case report
      and literature review.
AB  - A rare case of a 44-year-old Chinese male with diffuse idiopathic skeletal
      hyperostosis (DISH) and simultaneous ossification of the posterior longitudinal
      ligament (OPLL) and ossification of the ligamentum flavum (OLF) at T1-2 causing
      thoracic myelopathy is reported herein. Posterior decompression without
      extirpating the OPLL was performed at T1-2. Postoperatively, symptoms were
      greatly improved, with remaining hyperreflexia and Grade 4/5 muscle strength in
      the lower extremities. The Japanese Orthopedic Association score improved from 5
      preoperatively to 9 at final follow-up. The presence of a cyst due to leakage of
      cerebrospinal fluid was confirmed by MRI at day 27, but it resolved after
      conservative management. The clinical manifestation of DISH, the relationship
      among DISH, OPLL, and OLF, and management of thoracic myelopathy due to OPLL and
      OLF were reviewed.

PMID- 20697750
TI  - The Edwin Smith papyrus: a clinical reappraisal of the oldest known document on
      spinal injuries.
AB  - Dating from the seventeenth century B.C: . the Edwin Smith papyrus is a unique
      treatise containing the oldest known descriptions of signs and symptoms of
      injuries of the spinal column and spinal cord. Based on a recent "medically based
      translation" of the Smith papyrus, its enclosed treasures in diagnostic,
      prognostic and therapeutic reasoning are revisited. Although patient
      demographics, diagnostic techniques and therapeutic options considerably changed
      over time, the documented rationale on spinal injuries can still be regarded as
      the state-of-the-art reasoning for modern clinical practice.

PMID- 20697751
TI  - Cerebrospinal fluid insulin during non-neurological surgery.
AB  - Insulin plays an important metabolic and transmitter role in the central nervous
      system, but few studies have investigated the relationship between central and
      peripheral insulin concentrations. 35 patients undergoing knee surgery had
      cerebrospinal fluid (CSF) samples drawn before, 3 h after, and in the morning
      following surgery. Serum insulin concentrations increased after surgery and CSF
      insulin concentrations changed in the same direction with far smaller amplitude.
      These results indicate that the blood-brain barrier protects the brain from
      stress-induced peripheral hormonal fluctuations.

PMID- 20697752
TI  - Proline and hydroxyproline metabolism: implications for animal and human
      nutrition.
AB  - Proline plays important roles in protein synthesis and structure, metabolism
      (particularly the synthesis of arginine, polyamines, and glutamate via pyrroline
      5-carboxylate), and nutrition, as well as wound healing, antioxidative reactions,
      and immune responses. On a per-gram basis, proline plus hydroxyproline are most
      abundant in collagen and milk proteins, and requirements of proline for whole
      body protein synthesis are the greatest among all amino acids. Therefore,
      physiological needs for proline are particularly high during the life cycle.
      While most mammals (including humans and pigs) can synthesize proline from
      arginine and glutamine/glutamate, rates of endogenous synthesis are inadequate
      for neonates, birds, and fish. Thus, work with young pigs (a widely used animal
      model for studying infant nutrition) has shown that supplementing 0.0, 0.35, 0.7,
      1.05, 1.4, and 2.1% proline to a proline-free chemically defined diet containing
      0.48% arginine and 2% glutamate dose dependently improved daily growth rate and
      feed efficiency while reducing concentrations of urea in plasma. Additionally,
      maximal growth performance of chickens depended on at least 0.8% proline in the
      diet. Likewise, dietary supplementation with 0.07, 0.14, and 0.28% hydroxyproline
      (a metabolite of proline) to a plant protein-based diet enhanced weight gains of
      salmon. Based on its regulatory roles in cellular biochemistry, proline can be
      considered as a functional amino acid for mammalian, avian, and aquatic species.
      Further research is warranted to develop effective strategies of dietary
      supplementation with proline or hydroxyproline to benefit health, growth, and
      development of animals and humans.

PMID- 20697753
TI  - Genetic aspects of osteoporosis.
AB  - The multiple factors contributing to the pathogenesis of osteoporosis include
      genetic and environmental factors. Because decrease in bone mineral density (BMD)
      is the major clinical indicator and a useful quantitative trait, many association
      and linkage studies of BMD have been conducted. Although the series of studies
      showed apparently significant associations, the genes have not been found that
      can be utilized in clinical practice. Several genes identified in robust genome
      wide association studies will be the new cutting edge in genetic studies of
      osteoporosis. Our recent reports of functional single nucleotide polymorphism in
      the tissue-nonspecific alkaline phosphatase gene and gamma-carboxylase gene are
      presented in this review to discuss the future prospects in the genetic research
      of osteoporosis from the point of view of genome-nutrition interaction.

PMID- 20697754
TI  - Interaction between dietary conjugated linoleic acid and calcium supplementation
      affecting bone and fat mass.
AB  - Dietary conjugated linoleic acid (CLA) has shown wide biologically beneficial
      effects, such as anticancer, antiatherosclerotic, antidiabetic, immunomodulating,
      and antiobesity effects. However, the effects of CLA on total body ash,
      reflective of bone mineral content, have not been consistent. We hypothesized
      that the inconsistency of the CLA effect on ash may be linked to interaction
      between CLA and dietary calcium levels. Thus, we investigated the effects of CLA
      on body ash in conjunction with various calcium levels. Male ICR mice were fed
      three different levels of calcium (0.01, 0.5, and 1%) with or without 0.5% CLA
      for 4 weeks for Experiment 1 and separate CLA isomers at 0.22% level with 1%
      calcium in Experiment 2. CLA feeding reduced body fat regardless of dietary
      calcium level, whereas CLA supplementation increased body ash compared to control
      only in animals fed the 1% calcium. In Experiment 2 it was confirmed that this
      observation was associated with the trans-10, cis-12 CLA isomer, but not with the
      cis-9, trans-11 isomer. CLA administration with 1% dietary calcium significantly
      improved total ash percent (%) in femurs, confirming that CLA has the potential
      to be used to improve bone mass.

PMID- 20697755
TI  - Sealing proximal surfaces with polyurethane tape: three-year evaluation.
AB  - The purpose of this investigation was to test the safety and clinical effect of a
      new material for the treatment of proximal caries. In 50 patients with two
      proximal initial lesions, one of the lesions was randomly chosen and sealed with
      a thin polyurethane-dimethacrylate foil using bonding. The other lesion received
      oral home care and was left as the control. In clinical follow-ups after 6 and 12
      months and X-ray evaluation after 2 and 3 years, the sealants showed good
      retention, marginal adaptation, and color. No relevant significant differences in
      plaque accumulation or gingival status were found between sealed and control
      teeth. On the radiographs, almost all sealed and control lesions appeared stable,
      indicating an arrest of the lesion. In conclusion, sealing initial proximal
      lesions showed no clinical problems and mostly arrest of caries on bitewing
      radiographs.

PMID- 20697756
TI  - PTH(1-34)-induced changes in RANKL and OPG expression by human PDL cells modify
      osteoclast biology in a co-culture model with RAW 264.7 cells.
AB  - Parathyroid hormone (PTH) is widely accepted as an anabolic agent when
      administered intermittently. Here, we explored the influence of intermittent
      PTH(1-34) on the expression of local factors by human periodontal ligament (PDL)
      cells that modify osteoclast biology. This approach aimed at a further
      elucidation of the role of the hormone and of PDL cells in the regulation of
      periodontal tissue homeostasis and of repair processes. In a co-culture model of
      mature PDL cells and RAW 264.7 cells, intermittent PTH(1-34) induced an increased
      gene expression for tartrate-resistant acid phosphatase (+84%), cathepsin K
      (+56%), and vitronectin-receptor (+56%); and an enhanced resorptive activity of
      differentiated osteoclasts (+154%). These findings were correlated with a
      reduction of the osteoprotegerin (OPG)/receptor activator of nuclear factor
      kappaB ligand (RANKL) ratio in the presence of PTH(1-34; -44%). Similar results
      were obtained when RAW cells were cultured with the conditioned medium of PTH(1
      34)-stimulated PDL cells. In contrast, when less mature PDL cells were co
      cultured with RAW cells, PTH(1-34) induced an inhibition of osteoclastic
      differentiation (TRAP, -35%; cathepsin K, -28%; vitronectin-receptor, -35%), a
      reduction of the resorbed substrate area (-77%) and an increase of the OPG/RANKL
      ratio (+11%). The conditioned medium of PTH(1-34)-pretreated less mature PDL
      cells led to a down-regulation of the number and activity of multinucleated
      cells. These data indicate that intermittent PTH(1-34) modifies the expression of
      membrane-bound and secreted factors by PDL cells which then in turn alter
      osteoclast biology. The PDL cell response to PTH(1-34) is specific in terms of
      cell maturation and the mechanism involved.

PMID- 20697757
TI  - Healing of acute alveolar bone dehiscence following treatment with porous
      biphasic calcium phosphate in beagle dogs.
AB  - The purpose of the present study was to evaluate histologically in beagle dogs
      the healing in acute dehiscence type defects following treatment with open flap
      debridement (OFD) with or without porous biphasic calcium phosphate (PBCP).
      Alveolar bone dehiscence defects were surgically created bilaterally at the
      labial aspects of maxillary third incisors in 12 beagle dogs. After root
      conditioning with ethylenediaminetetraacetate, PBCP was filled in the defects and
      the contralaterals were cured with OFD. Two fluorochrome labelings were
      administered at the 7th and 11th weeks, respectively. Four dogs were killed at
      the 12, 16, and 24 weeks, respectively. Histological observations were processed
      through microcomputed tomographic imaging, fluorescence microscope, and light
      microscopy. The formation of new regenerated tissues was assessed
      histomorphometrically. The results revealed the healing after treatments with
      PBCP evidenced a new attachment apparatus and that with OFD supported periodontal
      repair. In PBCP groups, the amount of new bone varied from 1.15 to 3.86 mm (23
      77.2% of the original defect size), while only 0.3 to 1.04 mm (6-20.8%) in OFD
      group. The amount of new cementum in PBCP varied from 1.18 to 4.16 mm (23.6
      82.3%), while only 0.67 to 1.15 mm (13.4-23%) in OFD group. The amount of
      periodontal ligament in PBCP varied from 1.03 to 4.12 mm (20.6-82.4%), while only
      0 to 0.93 mm (0-18.6%) in OFD group. There was significantly more regenerated
      tissue in PBCP groups compared to OFD procedures (p < 0.01). The present results
      indicate that PBCP may enhance periodontal regeneration in acute-type labial
      dehiscence defects.

PMID- 20697758
TI  - Diffusion of peroxides through dentine in vitro with and without prior use of a
      desensitizing varnish.
AB  - Different bleaching regimens are used in dentistry possibly penetrating the
      dentine and affecting the pulp. The aim of the present study was to investigate
      peroxide diffusion through dentine pre-treated with a desensitizing varnish
      (Vivasens(r)) in a standardized in vitro setup during application of different
      bleaching materials. The penetration was tested using 1.3-mm-thick bovine dentine
      slabs. The following bleaching materials were tested with and without prior
      application of the desensitizing varnish on the external side of the dentine
      slabs: Vivastyle, Whitestrips, Simply White, Opalescence (external bleaching),
      and sodium perborate (internal bleaching, only tested without varnish; n = 8
      samples per subgroup). The penetration of peroxides was measured photometrically
      using 4-aminoantipyrin as a substrate, the penetration of peroxides was monitored
      over 240 min. All bleaching agents yielded a diffusion of peroxides through the
      dentine, the kinetics of penetration were approximately linear for all materials
      tested. The significantly highest diffusion of peroxides was observed with
      Opalescence, the lowest with sodium perborate. The adoption of the desensitizing
      varnish reduced the diffusion of peroxides significantly for all external
      bleaching materials. Peroxides penetrated the dentine during application of
      bleaching materials; the penetration of peroxides can be reduced by application
      of a desensitizing agent.

PMID- 20697759
TI  - Molecular dynamics simulations of the minor ampullate spidroin modular amino acid
      sequence from Parawixia bistriatra: insights into silk tertiary structure and
      fibre formation.
AB  - Spider fibres are primarily composed of proteins that are secreted by specialised
      glands found in different groups of arthropods. Because of their unique
      mechanical characteristics, it is of great interest to understand how the
      influence of repetitive modules within the fibres affects the final protein
      structure. Because each fibre is composed of a diverse set of repeated modular
      sequences, the differences between fibres allow for their structural comparison
      and, thereby, their functional comparison. Herein, we present molecular dynamics
      simulations of partial sequences from minor ampullate Spidroin (MiSp) silk of the
      Brazilian species Parawixia bistriata. Our data show that the formation of beta
      sheet structures is directly related to the N-termini alignment of the modules.
      The N-terminal alignment gives rise to a high number of hydrogen bonds whose
      formation is driven by repeated alanine (Ala) sequences, which, in turn, lead to
      increased fibre strength. This increased fibre strength contributes significantly
      to the final tertiary structure of the silk.

PMID- 20697760
TI  - Structure-based in-silico rational design of a selective peptide inhibitor for
      thymidine monophosphate kinase of mycobacterium tuberculosis.
AB  - Tuberculosis still remains one of the most deadly infectious diseases. The
      emergence of drug resistant strains has fuelled the quest for novel drugs and
      drug targets for its successful treatment. Thymidine monophosphate kinase (TMPK)
      lies at the point where the salvage and de novo synthetic pathways meet in
      nucleotide synthesis. TMPK in M.tb has emerged as an attractive drug target since
      blocking it will affect both the pathways involved in the thymidine triphosphate
      synthesis. Moreover, the unique differences at the active site of TMPK enzyme in
      M.tb and humans can be exploited for the development of ideal drug candidates.
      Based on a detailed evaluation of known inhibitors and available three
      dimensional structures of TMPK, several peptidic inhibitors were designed. In
      silico docking and selectivity analysis of these inhibitors with TMPK from M.tb
      and human was carried out to examine their differential binding at the active
      site. The designed tripeptide, Trp-Pro-Asp, was found to be most selective for
      M.tb. The ADMET analysis of this peptide indicated that it is likely to be a drug
      candidate. The tripeptide so designed is a suitable lead molecule for the
      development of novel TMPK inhibitors as anti-tubercular drugs.

PMID- 20697761
TI  - 3D-QSAR and molecular docking studies of azaindole derivatives as Aurora B kinase
      inhibitors.
AB  - The Aurora kinases have been regarded as attractive targets for the development
      of new anticancer agents. Recently a series of azaindole derivatives with Aurora
      B inhibitory activities were reported. To explore the relationship between the
      structures of substituted azaindole derivatives and their inhibition of Aurora B,
      3D-QSAR and molecular docking studies were performed on a dataset of 41
      compounds. 3D-QSAR, including CoMFA and CoMSIA, were applied to identify the key
      structures impacting their inhibitory potencies. The CoMSIA model showed better
      results than CoMFA, with r(2)(cv) value of 0.575 and r(2) value of 0.987. 3D
      contour maps generated from CoMFA and CoMSIA along with the docking binding
      structures provided enough information about the structural requirements for
      better activity. Based on the structure-activity relationship revealed by the
      present study, we have designed a set of novel Aurora B inhibitors that showed
      excellent potencies in the developed models. Thus, our results allowed us to
      design new derivatives with desired activities.

PMID- 20697762
TI  - Evaluation of the effects of vitamin D receptor and estrogen receptor 1 gene
      polymorphisms on bone mineral density in postmenopausal women.
AB  - The aim of this study is to evaluate the effects of estrogen receptor 1 (ESR1)
      and vitamin D receptor (VDR) gene polymorphisms on bone mineral density (BMD) in
      a group of previously untreated osteoporotic women. Effects of demographic,
      environmental, and hormonal factors were also evaluated in this context. Fifty
      women who did not have a prior diagnosis or treatment of osteoporosis were
      compared with 50 nonosteoporotic postmenopausal women. Demographic and
      morphometric characteristics, medical history, dietary habits, exercise history,
      and sunlight exposure were recorded. The diagnosis of osteoporosis was made with
      regard to BMD measurements with DEXA. Blood samples were obtained for serum
      biochemistry, bone turnover markers, and VDR and ESR1 gene polymorphism analysis.
      Polymorphic sites of VDR and ESR1 genes were amplified by polymerase chain
      reaction and examined using restriction fragment length polymorphism. Bb genotype
      was significantly higher in the osteoporotic group when compared to controls
      (p=0.022). Each 1 U decrease in the body mass index (BMI) increased the risk of
      osteoporosis by 8% independent of the genotype. We could not observe a
      significant effect of ESR1 polymorphism on BMD or osteoporosis risk. The
      interaction of ApaI and BsmI genotypes were found to be significant (p=0.041) and
      the AaBb genotype, when corrected for BMI, was shown to increase the risk of
      osteoporosis five times (p=0.005). However, the results demonstrated
      insignificant p values when correction for multiple testing was performed with
      the Bonferroni method in the logistic regression model. A predominance of Bb
      genotype of the VDR gene was evident in this group of postmenopausal Turkish
      women. Moreover, the combined genotype AaBb conferred a five times increased risk
      for osteoporosis when corrected for clinical variables.

PMID- 20697763
TI  - Bone erosion repair with adalimumab in rheumatoid arthritis.

PMID- 20697764
TI  - Low bone mineral density is related to male gender and decreased functional
      capacity in early spondylarthropathies.
AB  - The objective of this study was to determine the prevalence and risk factors of
      low bone mineral density (BMD) in patients with spondylarthropathies (SpA) at an
      early stage of disease. In this cross-sectional study, the BMD of lumbar spine
      and hips was measured in 130 consecutive early SpA patients. The outcome measure
      BMD was defined as (1) osteoporosis, (2) osteopenia, and (3) normal bone density.
      Logistic regression analyses were used to investigate relations between the
      following variables: age, gender, disease duration, diagnosis, HLA-B27,
      erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Bath Ankylosing
      Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis
      Functional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI),
      extra-spinal manifestations and medication, with outcome measure low BMD
      (osteopenia and/or osteoporosis). The SpA population had a median time since
      diagnosis of 6.6 months and a disease duration of 6.3 years. In total, 9% of the
      early SpA patients had osteoporosis, 38% osteopenia, and 53% normal BMD. On
      univariate analyses, male gender, diagnosis of ankylosing spondylitis, increased
      CRP, high BASFI, and high BASMI were significantly associated with low BMD.
      Factors showing a relation with low BMD in the multivariate model were male
      gender (OR 4.18, 95% confidence interval (CI) 1.73-10.09), high BASMI (OR 1.54,
      95% CI 1.14-2.07), and high BASFI (OR 1.18, 95% CI 1.00-1.39). In early SpA
      patients, a high frequency (47%) of low BMD in femur as well as in lumbar spine
      was found. Low BMD was associated with male gender and decreased functional
      capacity. These findings emphasize the need for more alertness for osteoporosis
      and osteopenia in spondylarthropathy patients at an early stage of the disease.

PMID- 20697765
TI  - Combined meta-genomics analyses unravel candidate genes for the grain dietary
      fiber content in bread wheat (Triticum aestivum L.).
AB  - Grain dietary fiber content in wheat not only affects its end use and
      technological properties including milling, baking and animal feed but is also of
      great importance for health benefits. In this study, integration of association
      genetics (seven detected loci on chromosomes 1B, 3A, 3D, 5B, 6B, 7A, 7B) and meta
      QTL (three consensus QTL on chromosomes 1B, 3D and 6B) analyses allowed the
      identification of seven chromosomal regions underlying grain dietary fiber
      content in bread wheat. Based either on a diversity panel or on bi-parental
      populations, we clearly demonstrate that this trait is mainly driven by a major
      locus located on chromosome 1B associated with a log of p value >13 and a LOD
      score >8, respectively. In parallel, we identified 73 genes differentially
      expressed during the grain development and between genotypes with contrasting
      grain fiber contents. Integration of quantitative genetics and transcriptomic
      data allowed us to propose a short list of candidate genes that are conserved in
      the rice, sorghum and Brachypodium chromosome regions orthologous to the seven
      wheat grain fiber content QTL and that can be considered as major candidate genes
      for future improvement of the grain dietary fiber content in bread wheat breeding
      programs.

PMID- 20697766
TI  - Spontaneous cerebellar hemorrhage--experience with 57 surgically treated patients
      and review of the literature.
AB  - The treatment of spontaneous cerebellar hemorrhage is still discussed
      controversially. We analyzed a series of 57 patients who underwent surgical
      evacuation of a cerebellar hematoma at our department. Preoperative clinical and
      radiological parameters were assessed and correlated with the clinical outcome in
      order to identify factors with impact on outcome. The overall clinical outcome
      according to the Glasgow Outcome Scale at the last follow-up was good (GOS 4-5)
      in 27 patients (47%) and poor (GOS 2-3) in 16 patients (28%). Fourteen patients
      (25%) died. The initial neurological condition and the level of consciousness
      proved to be significant factors determining clinical outcome (p = 0.0032 and p =
      0.0001, respectively). Among radiological parameters, brain stem compression and
      a tight posterior fossa solely showed to be predictive for clinical outcome (p =
      0.0113 and p = 0.0167, respectively). Overall, our results emphasize the
      predictive impact of the initial neurological condition on clinical outcome
      confirming the grave outcome of patients in initially poor state as reported in
      previous studies. The hematoma size solely, in contrast to previous observations,
      showed not to be predictive for clinical outcome. Especially for the still
      disputed treatment of patients in good initial neurological condition, a
      suggestion can be derived from the present study. Based on the excellent outcome
      of patients with good initial clinical condition undergoing surgery due to
      secondary deterioration, we do not recommend preventive evacuation of a
      cerebellar hematoma in these patients.

PMID- 20697767
TI  - Recruitment of intuitive versus analytic thinking strategies affects the role of
      working memory in a gambling task.
AB  - Previous studies found mixed results concerning the role of working memory (WM)
      in the gambling task (GT). Here, we aimed at reconciling inconsistencies by
      showing that the standard version of the task can be solved using intuitive
      strategies operating automatically, while more complex versions require analytic
      strategies drawing on executive functions. In Study 1, where good performance on
      the GT could be achieved using intuitive strategies, participants performed well
      both with and without a concurrent WM load. In Study 2, where analytical
      strategies were required to solve a more complex version of the GT, participants
      without WM load performed well, while participants with WM load performed poorly.
      In Study 3, where the complexity of the GT was further increased, participants in
      both conditions performed poorly. In addition to the standard performance
      measure, we used participants' subjective expected utility, showing that it
      differs from the standard measure in some important aspects.

PMID- 20697768
TI  - Better health reports when the grass is greener on your side of the fence?: a
      cross-sectional study in older persons.
AB  - OBJECTIVE: To study whether the luxury goods make older people feel in better
      health and whether this association is similar in higher and lower social
      classes. METHODS: SMILE consists of a Dutch general population consisting of
      2.637 men and women aged 60 years and older in 2007. The SF-36 was used to
      measure health-related functioning. RESULTS: In the lower social class, having
      many luxury goods was related to feeling in better physical (OR 2.06, 95% CI 1.39
      3.07) and mental health (OR 1.79, 95% CI 1.21-2.64), but not in the higher social
      class. CONCLUSIONS: There might be a health benefit of keeping up appearances,
      snobbism, and "conspicuous consumption" in older people from lower social
      classes.

PMID- 20697769
TI  - Evaluating the decisional balance construct of the Transtheoretical Model: are
      two dimensions of pros and cons really enough?
AB  - OBJECTIVES: The Transtheoretical Model of behavior change (TTM) postulates that
      behavior change is a process involving progress through five distinct stages of
      change (SOC). One of the key components for progress to a later stage is
      decisional balance (pros and cons of changing to the target behavior). The goal
      of the present study is to test the two dimensions of decisional balance as
      postulated in the TTM in the context of exercising behavior. METHODS: The
      analyses are based on data from an online survey of 266 freshman students at the
      University of Zurich; participants self-reported their frequency of exercising
      and their weighing of the importance of 49 pros and cons of exercising. RESULTS:
      The results indicate that a two-dimensional solution of decisional balance is
      insufficient. The analysis of pros and cons of exercising yielded a seven-factor
      solution with in part different progressions through the SOC. CONCLUSIONS: With
      the subdivision into different pros and cons, intervention programs can be
      developed that better match the needs of participants in terms of fostering and
      decreasing the most important pros and cons of exercising.

PMID- 20697771
TI  - Water, ecology, and health.

PMID- 20697770
TI  - Targeting abnormal DNA double strand break repair in cancer.
AB  - A major challenge in cancer treatment is the development of therapies that target
      cancer cells with little or no toxicity to normal tissues and cells. Alterations
      in DNA double strand break (DSB) repair in cancer cells include both elevated and
      reduced levels of key repair proteins and changes in the relative contributions
      of the various DSB repair pathways. These differences can result in increased
      sensitivity to DSB-inducing agents and increased genomic instability. The
      development of agents that selectively inhibit the DSB repair pathways that
      cancer cells are more dependent upon will facilitate the design of therapeutic
      strategies that exploit the differences in DSB repair between normal and cancer
      cells. Here, we discuss the pathways of DSB repair, alterations in DSB repair in
      cancer, inhibitors of DSB repair and future directions for cancer therapies that
      target DSB repair.

PMID- 20697772
TI  - In vivo and in vitro assessment of the action of SN 28049, a benzonaphthyridine
      derivative targeting topoisomerase II, on the murine Colon 38 carcinoma.
AB  - AIM: SN 28049 (N-[2-(dimethylamino)ethyl]-2,6-dimethyl-1-oxo-1,2-dihydrobenzo[b]
      1,6-naphthyridine-4-carboxamide) is a new DNA binding drug that targets
      topoisomerase II. SN 28049 is curative against the murine Colon 38 adenocarcinoma
      (CT38) while etoposide, another topoisomerase II-directed drug, shows minimal
      activity; we investigated the basis for this difference in vivo and in vitro.
      METHODS: Colon 38 tumours were grown in C57Bl mice and in immunodeficient mice.
      Tumour sections were examined by staining and TUNEL assays. A new cell line (Co
      38P) derived from the in vivo tumour was developed and responses were analysed
      using flow cytometry. RESULTS: Both SN 28049 and etoposide induced similar tumour
      histological changes, reducing mitotic index and increasing apoptotic index 8 h
      after administration. At later times however, SN 28049-treated tumours showed
      further progressive morphological changes while etoposide-treated tumours
      reverted to their original growth characteristics. The effects of SN 28049 on
      tumour growth were delayed and attenuated when Colon 38 tumours were grown in
      immunodeficient mice. SN 28049 and etoposide both induced dose-dependent
      increases of gamma-phosphorylation of histone H2AX and cell cycle perturbation of
      the Co-38P cell line, indicative of DNA damage, although SN 28049 had 30-fold
      higher activity. Following 1-hour drug exposure of Co-38P cells, SN 28049 was
      more effective that etoposide in inducing persistent cycle arrest for the same
      degree of DNA damage. CONCLUSION: The superior antitumour activity of SN 28049
      may result from its ability to induce long term cycle arrest. Host immune
      responses contribute to the curative activity of SN 28049 and this could result
      from the induction of cycle arrest.

PMID- 20697773
TI  - Synthesis and antitumor activity of novel aroylthiourea derivatives of
      podophyllotoxin.
AB  - A novel series of 4beta-[(4-substituted) aroylthiourea] derivatives of
      podophyllotoxin were synthesized and their abilities to inhibit the growth of
      cancer cells were investigated by MTT assay. Compound 4a possessed the highest
      cytotoxicity on HepG2, A549 and HCT-116 cancer cell lines with the IC(50) values
      of 0.1 MUM. Apoptosis in HCT-116 cells induced by compound 4a was observed by
      Hoechst33342-Propidium iodide (PI) and acridine orange (AO)-ethidium bromide (EB)
      double staining assays. DNA flow cytometric analysis revealed that 4a induced
      cell cycle arrest at G2/M phase and kDNA decatenation assay indicated that 4a
      inhibited topoisomerase IIalpha-mediated kDNA decatenation. Our results indicated
      that compound 4a possessed promising antitumor activity, which need to be studied
      further.

PMID- 20697774
TI  - A phase I dose escalation study of TTI-237 in patients with advanced malignant
      solid tumors.
AB  - PURPOSE: This study was to determine the maximum tolerated dose, dose-limiting
      toxicities, and pharmacokinetic profile of TTI-237, a novel anti-tubulin drug,
      administered weekly in patients with refractory solid tumors. PATIENTS AND
      METHODS: Using an accelerated dose escalation design, patients with refractory
      solid tumors were enrolled in this study and treated with TTI-237 intravenously
      on days 1, 8 and 15 of a 28-day cycle. The starting dose was 4.5 mg/m(2).
      Pharmacokinetic studies were performed in patients at all dose levels. RESULT:
      Twenty-eight patients were enrolled and treated with TTI-237 at dose of 4.5, 9,
      15, 22.5 and 31.5 mg/m(2). One dose-limiting toxicity neutropenia fever was
      observed at 31.5 mg/m(2), and all seven patients developed grade 3 or 4
      neutropenia at that dose level. TTI-237 dosage was de-escalated to 22.5 and 18
      mg/m(2). Six patients were treated at the 18 mg/m(2) dose level without dose
      limiting toxicity prior to trial termination. The mean terminal-phase elimination
      half-life (t(1/2)) for TTI-237 was 25-29 h, and the mean area under the
      concentration time curve at 31.5 mg/m(2) was 2,768 ng*h/mL. CONCLUSION: A
      protocol defined maximum tolerated dose was not determined because of early
      termination of the TTI-237 trial by the sponsor. 18 mg/m(2) may be a tolerable
      dose of TTI-237.

PMID- 20697775
TI  - Phase I study of gemcitabine, docetaxel and imatinib in refractory and relapsed
      solid tumors.
AB  - PURPOSE: In a phase I study, the combination of gemcitabine and imatinib was well
      tolerated with broad anticancer activity. This phase I trial evaluated the
      triplet of docetaxel, gemcitabine and imatinib. EXPERIMENTAL DESIGN: Imatinib was
      administered at 400 mg daily on days 1-5, 8-12 and 15-19. Gemcitabine was started
      at 600 mg/m(2) at a rate of 10 mg/min on days 3 and 10 and docetaxel at 30
      mg/m(2) on day 10, on a 21-day cycle. Diffusion and dynamic contrast-enhanced
      perfusion MRI was performed in selected patients. RESULTS: Twenty patients with
      relapsed/refractory solid tumors were enrolled in this IRB-approved study. The
      mean age was 64, and mean ECOG PS was 1. Two patients were evaluated by
      diffusion/perfusion MRI. After two grade 3 hematological toxicities at dose level
      1, the protocol was amended to reduce the dose of imatinib. MTDs were 600 mg/
      m(2) on days 3 and 10 for gemcitabine, 30 mg/ m(2) on day 10 for docetaxel, and
      400 mg daily on days 1-5 and 8-12 for imatinib. Dose limiting toxicities after
      one cycle were neutropenic fever, and pleural and pericardial effusions. The best
      response achieved was stable disease, for six cycles, in one patient each with
      mesothelioma and non small cell lung cancer (NSCLC) at the MTD. Two patients with
      NSCLC had stable disease for four cycles. DISCUSSION: An unexpectedly low MTD for
      this triplet was identified. Our results suggest drug-drug interactions that
      amplify toxicities with little evidence of improved tumor control.

PMID- 20697777
TI  - Assessing the impact of non-dilating the eye on full-field electroretinogram and
      standard flash response.
AB  - We investigated the possibility of performing electroretinography (ERG) in non
      pharmacologically dilated eyes using brighter flash (time-integrated) luminance.
      Photopic (N = 26; background 25.5 cd.m(-2), white LED flashes) and scotopic ERG
      (N = 23, green LED flashes) luminance response functions were obtained
      simultaneously in a dilated (DE) and non-dilated eye (NDE). In the NDE, photopic
      V (max) b-wave amplitude was reduced by 14% (P < 0.0001), implicit time prolonged
      (P < 0.0001), and retinal sensitivity (log K) decreased by 0.38 log units (P <
      0.0001) with no effect on a-wave. Using a xenon strobe light (N = 6) to increase
      flash luminance, V (max) remained lower by about 12% in the NDE (P = 0.02). V
      (max) with LED and xenon was achieved at 3.9 +/- 1.0 cd.s.m(-2) and 3.3 +/- 0.81
      cd.s.m(-2) in the DE and 10.6 +/- 1.2 cd.s.m(-2) and 12.3 +/- 1.90 cd.s.m(-2) in
      the NDE, that is an increase of 0.43 and 0.57 log unit (P < 0.0001),
      respectively. Increasing background luminance by 0.50 log units (80 cd.m(-2), N =
      4) resulted in implicit time normalization but not V (max) amplitude. Rod V (max)
      was decreased by 7% in NDE (P < 0.05) and sensitivity reduced by 0.40 log units
      (P < 0.0001), but our data suggest that the luminance may have not been
      sufficient to reach V (max) in all participants in the NDE and that the
      sensitivity change may have been due to an inadequate inter-stimulus interval.
      For the photopic ERG, increasing flash luminance is not sufficient to compensate
      for the smaller pupil size, whereas for the scotopic ERG, more data are needed to
      establish proper inter-stimulus interval to perform recordings in a non
      pharmacologically dilated.

PMID- 20697778
TI  - Mechanisms of amphipathic helical peptide denaturation by guanidinium chloride
      and urea: a molecular dynamics simulation study.
AB  - Urea and GdmCl are widely used to denature proteins at high concentrations. Here,
      we used MD simulations to study the denaturation mechanisms of helical peptide in
      different concentrations of GdmCl and urea. It was found that the helical
      structure of the peptide in water simulation is disappeared after 5 ns while the
      helicity of the peptide is disappeared after 70 ns in 2 M urea and 25 ns in 1 M
      GdmCl. Surprisingly, this result shows that the helical structure in low
      concentration of denaturants is remained more with respect to that solvated in
      water. The present work strongly suggests that urea interact more preferentially
      to non-polar and aromatic side chains in 2 M urea; therefore, hydrophobic
      residues are in more favorable environment in 2 M urea. Our results also reveal
      that the hydrogen bonds between urea and the backbone is the dominant mechanism
      by which the peptide is destabilized in high concentration of urea. In 1 M and 2
      M GdmCl, GdmCl molecules tend to engage in transient stacking interactions with
      aromatics and hydrophobic planar side chains that lead to displacement of water
      from the hydration surface, providing more favorable environment for them. This
      shows that accumulation of GdmCl around hydrophobic surfaces in 1 M and 2 M GdmCl
      solutions prevents proper solvation of the peptide at the beginning. In high
      GdmCl concentrations, water solvate the peptide better than 1 M and 2 M GdmCl.
      Therefore, our results strongly suggest that hydrogen bonds between water and the
      peptide are important factors in the destabilization of peptide in GdmCl
      solutions.

PMID- 20697779
TI  - Bioavailability, mobility, and toxicity of Cu in soils around the Dexing Cu mine
      in China.
AB  - Total concentration is not a reliable indicator of Cu mobility or its
      bioavailability in soils. The chemical fraction determines the behavior of Cu in
      soils and hence its toxicity for terrestrial biota. We used the sequential
      extraction procedure and barley toxicity tests to examine the transfer of Cu in
      soils around the Dexing Cu mine and to make an ecological risk assessment of Cu
      in this area. The bioavailable Cu (exchangeable Cu and carbonate-bound Cu) in
      each soil profile did not change significantly with soil depth, indicating that
      the Cu itself was vertically mobile and thus potentially a higher risk to the
      environment. Cu toxicity and bioaccumulation in plants varied with the soil
      physicochemical characteristics [e.g., pH, clay content, and cation exchange
      capacity (CEC)] and the level of bioavailable Cu. Multiple regression analysis
      revealed that bioavailable Cu and CEC could be used to predict Cu toxicity to
      barley and that other characteristics (such as soil pH, clay content, or total
      organic carbon) did not predict the risk of toxicity as well as CEC. For the soil
      to be suitable for agriculture use, treatment of the local soil contamination
      with guest soil reclamation and phytoremediation with heavy metal-resistant
      plants would be necessary.

PMID- 20697780
TI  - Effects of dietary fat on spontaneous metastasis of Lewis lung carcinoma in mice.
AB  - The present study assessed the effects of dietary fat on spontaneous metastasis
      of Lewis lung carcinoma in mice. Three-week old male C57BL/6 mice were fed the
      AIN-93G diet or a 45% fat diet (% kcal.) for 7 weeks before they were
      subcutaneously injected with 2.5 * 105 viable carcinoma cells. The primary tumor
      was resected 2 weeks later, and mice were maintained on their respective diets
      for an additional 2 weeks. The high-fat diet significantly increased body weight
      and abdominal adipose weight compared to the AIN-93G diet. Feeding mice the 45%
      fat diet resulted in a two-fold increase in the number of lung metastases (P <
      0.05), a 35% increase in tumor cross-sectional area, and a 50% increase in tumor
      volume compared to mice fed the AIN-93G diet. There were no differences in plasma
      concentrations of TIMP-1, IL-1beta, VEGF and MCP-1 in non-tumor-bearing mice fed
      the AIN-93G diet or the high-fat diet, but significant increases in these
      cytokines in tumor-bearing mice fed the AIN-93G diet compared to the non-tumor
      bearing mice fed the same diet (P < 0.05 for each comparison). Further
      significant increases in these cytokines in tumor-bearing mice fed the 45% fat
      diet compared to the same tumor-bearing mice fed the AIN-93G diet (P < 0.05 for
      each comparison). The high-fat diet significantly increased plasma leptin and
      significantly decreased plasma adiponectin compared to the AIN-93G diet in both
      non-tumor-bearing and tumor-bearing mice. Results of the present study
      demonstrated that the high-fat diet enhanced spontaneous metastasis of Lewis lung
      carcinoma in mice and that this aggressiveness was accompanied with significant
      increases in plasma concentrations of angiogenic cytokines, suggesting that
      dietary fat affects metastasis by promoting angiogenic processes.

PMID- 20697781
TI  - Using thermally stimulated current (TSC) to investigate disorder in micronized
      drug substance produced at different milling energies.
AB  - PURPOSE: To investigate the use of thermally stimulated current (TSC) to
      characterize disorder resulting from micronization of a crystalline drug
      substance. Samples processed at different milling energies are characterized, and
      annealing studied. METHODS: Molecular mobility in micronized drug substance was
      studied using TSC and compared to results from differential scanning calorimetry
      (DSC). The micronized drug substance TSC spectra are compared to crystalline and
      amorphous references. RESULTS: TSC shows distinct relaxation modes for micronized
      material in comparison to a single weak exotherm observed with DSC. Molecular
      mobility modes are unique for micronized material compared to the amorphous
      reference indicating physically distinct disorder compared to phase-separated
      amorphous material. Signals are ascribed as arising from crystal defects. TSC
      differentiates material processed at different milling energies showing
      reasonable correlation between the AUC of the alpha-relaxation and micronization
      energy. The annealing process of crystal defects in micronized drug appears to
      proceed differently for alpha and beta relaxations. CONCLUSIONS: TSC proves
      sensitive to the crystal defects in the micronized drug substance studied here.
      The technique is able to differentiate distinct types of disorder and can be used
      to characterize noncrystalline regions arising from milling processes which are
      physically distinct from amorphous material.

PMID- 20697782
TI  - Anisotropic porous structure of pharmaceutical compacts evaluated by PGSTE-NMR in
      relation to mechanical property anisotropy.
AB  - PURPOSE: The pore space anisotropy of pharmaceutical compacts was evaluated in
      relation to the mechanical property anisotropy. METHODS: The topology and the
      pore space anisotropy were characterized by PGSTE-NMR measurements.
      Parallelepipedical compacts of anhydrous calcium phosphate (aCP) and
      microcrystalline cellulose (MCC) were tested on top, bottom and side faces. A
      microindentation and three-point single beam tests were used to measure Brinell
      hardness, tensile strength and Young's modulus. All the data were submitted to a
      statistical analysis to test for significance. RESULTS: The porous structure of
      MCC compacts was anisotropic, contrary to those of aCP. The analysis of the pore
      space by PGSTE-NMR method showed that its structural anisotropy was controlled by
      the behaviour under compaction of the excipients. At the same time, the Young's
      modulus and the tensile strength were the same whatever the direction of testing.
      For the aCP compacts, all the faces had the same Brinell hardness. With MCC
      compacts, only the bottom face showed a lower Brinell hardness. CONCLUSIONS:
      Except for Brinell hardness measured on MCC compacts, the tested samples were
      characterized by anisotropic mechanical properties when its porous structures
      were sometimes anisotropic. Then, there is not a straight link between porosity
      anisotropy and mechanical properties.

PMID- 20697783
TI  - Contact sex pheromone components of the seed beetle, Callosobruchus analis (F.).
AB  - Callosobruchus analis (Coleoptera: Chrysomelidae: Bruchinae), found throughout
      tropical Asia and Africa, is a pest of stored legumes. Previous work has shown
      that females of this species produce a contact sex pheromone that elicits
      copulatory behavior in males. Comparisons of copulatory activity between any two
      of four congeneric species suggest that the contact sex pheromones are species
      specific. In laboratory bioassays, male C. analis exhibited copulatory behavior
      to a female dummy to which a crude extract of virgin females was applied. The
      extract had been collected by a filter paper method and was purified by acid-base
      partition and chromatographic techniques. Gas chromatography-mass spectrometry
      (GC-MS) analyses of active fractions revealed that the active compounds were 2,6
      dimethyloctane-1,8-dioic acid (1) and callosobruchusic acid, (E)-3,7-dimethyl-2
      octene-1,8-dioic acid (2), previously identified as contact sex pheromones of
      Callosobruchus maculatus (F.) and C. chinensis (L.), respectively. The
      stereoisomeric and chemical compositions were determined by the 2D-HPLC-Ohrui
      Akasaka method as (2S,6R)-1:(S)-2=1.8:1, which meant that both compounds in C.
      analis were stereochemically pure, unlike the case of C. maculatus and C.
      chinensis. An examination of the influence of synthetic pheromone compounds on
      male copulatory activity revealed that (2S,6R)-1 is the main component, and that
      (S)-2 has an additive effect. In the examination of the stereochemistry-activity
      relationship, no copulatory behavior was elicited by (2R,6S)-1, and, furthermore,
      the enantiomer significantly masked the pheromonal activity of (2S,6R)-1. Glass
      rod dummy assays also suggested the presence of synergists. These results could
      elucidate the specificity of mate recognition in C. analis.

PMID- 20697784
TI  - First contact pheromone identified for a longhorned beetle (Coleoptera:
      Cerambycidae) in the subfamily Prioninae.
AB  - Little is known of the reproductive behavior of longhorned beetles (Coleoptera:
      Cerambycidae) in the subfamily Prioninae. Mallodon dasystomus (Say), the hardwood
      stump borer, is a widely distributed prionine that is native to the southern U.S.
      Here, we explored the chemically-mediated mating behavior of M. dasystomus, and
      tested the hypothesis that males recognize females by a contact pheromone. In
      mating bioassays, all males tested attempted to mate with females only after
      contacting females with their antennae. Moreover, all males attempted to mate
      with solvent-washed dead females treated with as little as 0.15 +/- 0.03 female
      equivalents of conspecific cuticular extracts, confirming that compounds on the
      cuticle of females are essential for mate recognition. Cuticular hydrocarbon
      profiles of females contained 13 compounds that were not present in profiles of
      males. Among the female-specific compounds, two co-dominant methyl-branched
      alkanes, 2-methylhexacosane (2Me-C(26)) and 2-methyloctacosane (2Me-C(28)),
      accounted for 17% of the total hydrocarbons. Our strategy for identifying the
      contact pheromone was to synthesize and test the bioactivity of female specific
      compounds, starting with the most abundant. In bioassays, males displayed mating
      behavior in response to synthetic 2Me-C(26) and 2Me-C(28) when tested
      individually. Furthermore, when these compounds were tested in combination, they
      elicited the full progression of mating behaviors, suggesting that 2Me-C(26) and
      2Me-C(28) make up the contact pheromone. These findings are further evidence of
      the critical role of contact pheromones in mating systems of longhorned beetles.

PMID- 20697785
TI  - Training physicians to do office-based smoking cessation increases adherence to
      PHS guidelines.
AB  - Cigarette smoking is the leading cause of preventable mortality and morbidity in
      the United States. Healthcare providers can contribute significantly to the war
      against tobacco use; patients advised to quit smoking by their physicians are 1.6
      times more likely to quit than patients not receiving physician advice. However,
      most smokers do not receive this advice when visiting their physicians. The
      Morehouse School of Medicine Tobacco Control Research Program was undertaken to
      develop best practices for implementing the "2000 Public Health Services Clinical
      Practice Guidelines on Treating Tobacco Use and Dependence" and the "Pathways to
      Freedom" tobacco cessation program among African American physicians in private
      practice and healthcare providers at community health centers. Ten focus groups
      were conducted; 82 healthcare professionals participated. Six major themes were
      identified as barriers to the provision of smoking cessation services. An
      intervention was developed based on these results and tested among Georgia
      community-based physicians. A total of 308 charts were abstracted both pre- and
      post-intervention. Charts were scored using a system awarding one point for each
      of the five "A's" recommended by the PHS guidelines (Ask, Advise, Assess, Assist,
      Arrange) employed during the patient visit. The mean pre-intervention five "A's"
      score was 1.29 compared to 1.90 post-intervention (P < 0.001). All charts had
      evidence of the first "A" ("asked") both pre- and post-intervention, and the
      other four "A's" all had statistically significant increases pre-to post
      intervention. CONCLUSIONS: The results demonstrate that, with training of
      physicians, compliance with the PHS tobacco guidelines can be greatly improved.

PMID- 20697786
TI  - Parental perception on the efficacy of a physical activity program for
      preschoolers.
AB  - Childhood obesity is among the leading health concerns in the United States. The
      relationship between unmet physical activity needs in young children is of
      particular interest as the trend in childhood obesity continues to rise and unmet
      physical activity needs are identified. The preschool years are an influential
      time in promoting healthful lifestyle habits and early childhood interventions
      may help establish lifelong healthful behaviors which could help prevent obesity
      later in life. The Food Friends(r): Get Movin' with Mighty Moves(r) is a
      preschool physical activity program which aims to improve children's gross motor
      skills and physical activity levels. The home environment and parental modeling
      are critical factors related to child physical activity in this population. The
      parent component, Mighty Moves(r): Fun Ways to Keep Families Active and Healthy,
      was designed to address barriers in the home environment that lead to unmet
      physical activity needs in preschoolers and their families. The program and
      materials were designed based on Social Marketing tenets and Social Learning
      Theory principles. Four Colorado Head Start centers were assigned to an
      experimental group as part of the Mighty Moves(r) group randomized trial.
      Quantitative and qualitative evaluation methods were used to determine what
      messages and materials reached and motivated the target audience to increase
      physical activity levels. Results of the study indicated the program's materials
      helped families and children to be more physically active. Additionally,
      materials and material dissemination were revised to enhance program goals.

PMID- 20697787
TI  - Language discordance and testing for latent tuberculosis infection among recent
      Asian and Latino immigrants.
AB  - The foreign-born population is disproportionately affected by tuberculosis (TB).
      Testing to identify persons with latent TB infection is critical. The aim of this
      study was to assess clinic-based testing for latent tuberculosis infection among
      recent Asian and Latino immigrants. A randomized controlled trial of interpreting
      methods and their impact on medical outcomes was conducted at the primary care
      clinic of a New York City municipal hospital. This study is a nested cohort of
      recruited patients with an indication to receive tuberculin testing, based on
      recent migration to the US from endemic areas. Medical record data were
      abstracted to determine referral for, and completion of, tuberculin testing.
      Bivariate analyses were used to test for differences in tuberculin testing
      between language concordant and discordant groups. Seven hundred and eighty-two
      patients were enrolled. One hundred and ninety-one had migrated within 5 years of
      enrollment from endemic areas. None spoke English as a primary language. Seventy
      percentage of patient-provider encounters were language discordant. Seventeen of
      191 were referred for testing. Fifteen (88%) completed testing. Six (40%) had
      positive results. There were no significant differences between language
      concordant and discordant patients. In this at-risk population, every patient in
      clinical care should be considered for testing if indicated by country of origin.

PMID- 20697788
TI  - A national survey of mental health services available to offenders with mental
      illness: who is doing what?
AB  - The purpose of this study was to examine the national practices of psychotherapy
      services for male offenders with mental illness (OMI) in state correctional
      facilities. Participants consisted of 230 correctional mental health service
      providers from 165 state correctional facilities. Results indicated that mental
      health professionals provided a variety of services to OMI that can be
      conceptualized by six goals considered important in their work: mental illness
      recovery, emotions management, institutional functioning, re-entry, risk-need,
      and personal growth. Mental health professionals in this study generally viewed
      mental illness recovery, institutional functioning, and personal growth as
      significantly more important and spent more time focused on these goals than
      emotions management, re-entry, and risk-need. Mental health professionals tended
      to believe the services they provided were effective across four key treatment
      foci including mental illness, skill development, behavioral functioning, and
      criminogenic needs with more progress perceived in areas related to mental
      illness and skill development than their ability to effectively change behavioral
      functioning. Implications of these findings and directions for future research
      are discussed.

PMID- 20697789
TI  - Adrenomedullin inhibits IL-1beta-induced rheumatoid synovial fibroblast
      proliferation and MMPs, COX-2 and PGE2 production.
AB  - To determine the effects of adrenomedullin (AM) on interleukin (IL)-1beta-induced
      proliferation of rheumatoid synovial fibroblasts (RASFs) and production of matrix
      metalloproteinases (MMPs), cyclooxygenase (COX) and prostaglandin E2 (PGE2) by
      RASFs. The RASFs proliferation was evaluated with CCK-8 reagent in the presence
      of IL-1beta with/without AM (1-52) and AM inhibitor (AM (22-52)). MMPs, tissue
      inhibitor of metalloproteinase (TIMP-1), COXs, PGE2 and intracellular mitogen
      activated protein kinase (MAPK) signalings, including p-ERK, p-p38, p-JNK were
      examined by immunoblotting or semiquantitative RT-PCR and ELISA. AM (1-52)
      inhibited IL-1beta-induced RASFs proliferation and inhibited MMP-1, 3, COX-2 and
      PGE2 production. AM (1-52) also inhibited IL-1beta-induced phosphorylation of ERK
      1/2, p38, JNK. AM 22-52 inhibited the effects of AM (1-52) on proliferation of
      RASFs and production of MMP-1, 3, COX-2 via MAPKs. These results suggest that AM
      might involved joint destruction in rheumatoid arthritis and indicate that it
      might be a new therapeutic modality for management of this disease.

PMID- 20697790
TI  - Comparative power spectral analysis of simultaneous elecroencephalographic and
      magnetoencephalographic recordings in humans suggests non-resistive extracellular
      media.
AB  - The resistive or non-resistive nature of the extracellular space in the brain is
      still debated, and is an important issue for correctly modeling extracellular
      potentials. Here, we first show theoretically that if the medium is resistive,
      the frequency scaling should be the same for electroencephalogram (EEG) and
      magnetoencephalogram (MEG) signals at low frequencies (<10 Hz). To test this
      prediction, we analyzed the spectrum of simultaneous EEG and MEG measurements in
      four human subjects. The frequency scaling of EEG displays coherent variations
      across the brain, in general between 1/f and 1/f(2), and tends to be smaller in
      parietal/temporal regions. In a given region, although the variability of the
      frequency scaling exponent was higher for MEG compared to EEG, both signals
      consistently scale with a different exponent. In some cases, the scaling was
      similar, but only when the signal-to-noise ratio of the MEG was low. Several
      methods of noise correction for environmental and instrumental noise were tested,
      and they all increased the difference between EEG and MEG scaling. In conclusion,
      there is a significant difference in frequency scaling between EEG and MEG, which
      can be explained if the extracellular medium (including other layers such as dura
      matter and skull) is globally non-resistive.

PMID- 20697791
TI  - Promoting imitation in young children with autism: a comparison of reciprocal
      imitation training and video modeling.
AB  - The inability to imitate is a salient diagnostic marker for autism. It has been
      suggested that for children with autism, imitation may be a prerequisite skill
      that can assist in the development of various skills. Using a multiple baseline
      design across subjects, the purpose of this research was to determine if two
      interventions, reciprocal imitation training and video modeling were effective in
      promoting imitation acquisition in young children with autism. Six boys were
      matched across various features (i.e., age, language, autism severity) and
      randomly placed in a treatment condition. Results indicated that all six
      participants increased their imitation skills to varying degrees in both
      conditions, and imitation maintained and generalized at higher than baseline
      levels post treatment.

PMID- 20697792
TI  - Family report of ASD concomitant with depression or anxiety among US children.
AB  - The objective is to estimate prevalence of parent-reported depression or anxiety
      among children with ASD, and describe parental concerns for their children. The
      design is Analysis of National Survey of Children's Health, 2003-2004. The
      participants are a national sample of 102,353 parents. 311,870 (544/100,000)
      parents of children ages 4-17 in the US reported that their child was diagnosed
      with autism. 125,809 also reported that their child had depression or anxiety
      (219/100,000). These parents report substantially higher concerns about their
      child's self-esteem, academic success, and potential to be bullied. Clinicians
      should take into account that children with ASD may face increased risk of
      depression or anxiety in adolescence. Coordinated care addressing social and
      emotional health in addition to clinical attention is important in this
      population.

PMID- 20697793
TI  - Brief report: significant differences in perceived odor pleasantness found in
      children with ASD.
AB  - The aim of our study was to explore possible differences in estimation of odor
      pleasantness in children with autism spectrum disorders (ASD) compared to
      controls. Thirty-five patients with Asperger's syndrome and high functioning
      autism (mean age 10.8 +/- 3.6 years; 31 boys) were compared with 35 healthy
      control subjects (mean age 10.4 +/- 2.4 years; 28 boys). Odor pleasantness was
      assessed on a 5-point scale using the Sniffin' Sticks test (Identification part
      of the test). Patients with ASD, compared to healthy controls, perceived the
      smell of cinnamon and pineapple as significantly less pleasant (p < 0.05); at the
      trend level, the same was true of cloves (p < 0.1). The possibility of olfactory
      dysfunctions as an autism biomarker is discussed.

PMID- 20697794
TI  - Brief report: adaptive behavior and cognitive skills for toddlers on the autism
      spectrum.
AB  - This study examined adaptive behavior and cognitive skills for 125 toddlers on
      the autism spectrum using the recently updated Vineland-II and Bayley-III. Delays
      in adaptive skills were apparent at 2 years of age. As a group, toddlers on the
      autism spectrum had a profile of Vineland-II standard scores in which Motor
      Skills > Daily Living Skills > Socialization > Communication. Vineland-II scores
      were significantly correlated with Bayley-III Cognitive scores. Performance on
      the ADOS was significantly negatively correlated with Bayley-III Cognitive
      standard scores and standard scores in the Daily Living Skills and Communication
      domains of the Vineland-II. However, calibrated ADOS scores did not contribute
      significant variance to Vineland-II scores beyond that predicted by age and
      Bayley-III scores.

PMID- 20697795
TI  - The construction and validation of an abridged version of the autism-spectrum
      quotient (AQ-Short).
AB  - This study reports on the development and validation of an abridged version of
      the 50-item Autism-Spectrum Quotient (AQ), a self-report measure of autistic
      traits. We aimed to reduce the number of items whilst retaining high validity and
      a meaningful factor structure. The item reduction procedure was performed on data
      from 1,263 Dutch students and general population adults. The resulting 28-item AQ
      Short was subsequently validated in 3 independent samples, both clinical and
      controls, from the Netherlands and the UK. The AQ-Short comprises two higher
      order factors assessing 'social behavioral difficulties' and 'a fascination for
      numbers/patterns'. The clear factor structure of the AQ-Short and its high
      sensitivity and specificity make the AQ-Short a useful alternative to the full 50
      item version.

PMID- 20697796
TI  - Biomarker testing to estimate under-reported heavy alcohol consumption by persons
      with HIV initiating ART in Uganda.
AB  - Alcohol affects the transmission and treatment of HIV, yet may be under-reported
      in resource-limited settings. We compared self-reported alcohol consumption with
      levels of plasma carbohydrate-deficient transferrin (%CDT), a biomarker of heavy
      alcohol consumption, in persons initiating antiretroviral therapy in Uganda.
      Almost seven percent (6.7%) of persons reporting abstaining and 10% reporting
      consuming 1-40 drinks in the prior month tested positive for %CDT, and actual
      under-report may be higher due to low sensitivity of %CDT. These results suggest
      likely under-report in those reporting abstaining and current drinking. Improved
      identification of heavy alcohol consumption is needed for research and clinical
      purposes.

PMID- 20697797
TI  - Statins and pancreatic cancer risk: a nested case-control study.
AB  - OBJECTIVE: To investigate the relationship between statin use and pancreatic
      cancer risk. METHODS: A nested case-control study was conducted within the UK
      GPRD. Cases had a diagnosis of primary malignant neoplasia of the exocrine
      pancreas. Controls were matched with cases on general practice site, sex and year
      of birth. Exposure of interest was exposure to statins since entry into the GPRD
      until 1 year before the case diagnosis date. Conditional logistic regression
      analyses were used to generate ORs and 95% CI associated with statin use compared
      to non-use. RESULTS: A total of 1,141 pancreatic cancer cases and 7,954 controls
      were identified. Any use of a statin since entry into the GPRD (excluding the
      year prior to diagnosis) was not associated with the risk of pancreatic cancer OR
      0.93 (95% CI, 0.76-1.14). Neither dose nor duration of statin use affected
      pancreatic cancer risk. When dose and duration of statin use combined were
      assessed, no evidence of reduced risk was seen for long-term users of high-dose
      statins OR 0.71 (0.42-1.20). Statin type (simvastatin vs atorvastatin) was not
      associated with pancreatic cancer risk. CONCLUSION: Statin use at doses for
      managing hypercholesterolaemia, in a UK population, was not associated with the
      risk of exocrine pancreatic cancer.

PMID- 20697798
TI  - Reproductive factors, menopausal hormone therapy, and risk of non-Hodgkin,
      diffuse large B-cell and follicular lymphomas: a UK case-control study.
AB  - BACKGROUND: Most non-Hodgkin lymphoma (NHL) subtypes occur more among men than
      women. Since sex hormones may influence immune function, female hormones may be
      involved. To investigate the relationship between NHL subtypes and reproductive
      factors, findings from a UK population-based case-control study (1998-2003) are
      presented. METHODS: Female cases (n = 389) and controls (n = 394) aged 16-69
      reported their reproductive histories. Odds ratios (ORs) and 95% confidence
      intervals (CI) were computed using unconditional logistic regression. RESULTS: No
      associations were found for age at menarche, parity, or age at first child. Among
      postmenopausal women, hormone therapy (HT) users had risks of diffuse large B
      cell lymphoma (DLBCL) and follicular lymphoma (FL) below one compared to non
      users (OR = 0.7, 95% CI 0.5,1.2; OR = 0.6, 95% CI 0.4,1.0, respectively).
      Estimates agree with other reports: meta-analyses gave pooled ORs of 0.8 (95% CI
      0.6,0.9) for DLBCL and 1.0 (95% CI 0.8,1.2) for FL. In our study, ORs decreased
      with years of HT use: less and more than 5 years being 0.9 (95% CI 0.5,1.5) and
      0.6 (95% CI 0.3,1.1) for DLBCL (p-trend = 0.22), and 0.8 (95% CI 0.4,1.4) and 0.4
      (95% CI 0.2,0.9) for FL (p-trend = 0.06). CONCLUSION: For greater power to
      investigate the association of hormones with DLBCL, FL, and rarer NHL subtypes,
      pooling data through the International Lymphoma Epidemiology Consortium
      (InterLymph) is warranted.

PMID- 20697799
TI  - The delinquency outcomes of boys with ADHD with and without comorbidity.
AB  - This study examined the association between childhood ADHD and juvenile
      delinquency by examining data from the Pittsburgh ADHD Longitudinal Study (PALS),
      a follow-up study of individuals diagnosed with ADHD in childhood (ages 5-12) and
      recontacted in adolescence and young adulthood for yearly follow-up (age at first
      follow-up interview M = 17.26, SD = 3.17). Participants were 288 males with
      childhood ADHD and 209 demographically similar males without ADHD who were
      recruited into the follow-up study. Delinquency information gathered yearly
      during the second through eighth follow-up provided a comprehensive history of
      juvenile delinquency for all participants. Four childhood diagnostic groups [ADHD
      only (N = 47), ADHD + ODD (N = 135), ADHD + CD (N = 106), and comparison (N =
      209)] were used to examine group differences on delinquency outcomes. Analyses
      were conducted across three dimensions of delinquency (i.e., severity, age of
      initiation, and variety). Individuals with childhood ADHD + CD displayed
      significantly worse delinquency outcomes than the other three groups, across
      almost all indices of offending. When compared to comparison participants, boys
      with ADHD-only and ADHD + ODD in childhood displayed earlier ages of delinquency
      initiation, a greater variety of offending, and higher prevalence of severe
      delinquency. These findings suggest that although childhood ADHD + CD creates the
      greatest risk for delinquency, boys with ADHD-only and ADHD + ODD also appear at
      a higher risk for later offending. The patterns of offending that emerged from
      the PALS are discussed in the context of the relationship between ADHD,
      comorbidity, and delinquency.

PMID- 20697800
TI  - Fragment c gamma receptor gene polymorphisms and breast cancer risk in case
      control studies in Japanese, Japanese Brazilians, and non-Japanese Brazilians.
AB  - Previous studies showing the presence of antibodies against tumor-associated
      antigens in healthy individuals suggest that antibody-dependent cell cytotoxicity
      (ADCC) might play a role in the development of breast cancer. We hypothesized
      that functional polymorphisms in fragment c gamma receptor (FcgR) genes were
      associated with breast cancer risk. We conducted hospital-based case-control
      studies of patients aged 20-74 years with invasive breast cancer, and matched
      controls from medical checkup examinees in Nagano, Japan and from cancer-free
      patients in Sao Paulo, Brazil. A total of 869 pairs (403 Japanese, 80 Japanese
      Brazilians and 386 non-Japanese Brazilians) were genotyped for two single
      nucleotide polymorphisms (SNPs): a histidine (H)/arginine (R) polymorphism at
      position 131 of FcgRIIa (FcgRIIa H131R) and a valine (V)/phenylalanine (F)
      polymorphism at position 158 of FcgRIIIa (FcgRIIIa F158V). We found no
      statistically significant association between either of the two SNPs and breast
      cancer risk regardless of population. In analyses of the three populations
      combined, adjusted odds ratio (OR) was 0.93 [95% confidence interval (CI) 0.66
      1.32] for women with the R/R versus H/H genotype of the FcgRIIa H131R
      polymorphism and 1.04 (95% CI 0.69-1.57) for the V/V versus F/F genotype of the
      FcgRIIIa F158V polymorphism. On combination of the two SNPs, compared to women
      with both the R/R genotype of the FcgRIIa H131R polymorphism and F/F genotype of
      the FcgRIIIa F158V polymorphism, the adjusted OR for women with both the H/H and
      V/V genotype was 0.68 (95% CI 0.37-1.27). In conclusion, our findings suggest
      that ADCC might not play a major role in the etiology of breast cancer.

PMID- 20697801
TI  - Effect of neoadjuvant anthracycline-taxane-based chemotherapy in different
      biological breast cancer phenotypes: overall results from the GeparTrio study.
AB  - In order to explore the effect of neoadjuvant chemotherapy (NACT) on clinical mid
      course and pathological complete response (pCR) at surgery in different
      biological breast cancer subtypes. The GeparTrio study included 2,072 patients
      with operable or locally advanced breast cancer. After two cycles with docetaxel,
      doxorubicin and cyclophosphamide (TAC) patients were randomized according to
      their clinical response. Clinical and biological factors were assessed for
      predicting clinically mid-course response and pCR at surgery. The overall pCR
      rate, defined as no invasive residuals in breast and axilla, was 20.5%. The
      highest pCR rate of 57% was observed in patients below 40 years of age with
      triple negative or grade 3 tumors. Independent factors for mid-course response
      and pCR were: young age, non-T4 tumors, high grade, and hormone receptor status,
      the strongest single predictive factor. Within the biological subtypes, grading
      was an independent factor to predict pCR for luminal tumors, clinical tumor stage
      for the HER2 like tumors and age for the triple negative ones. Grading gave
      independent information for mid-course response within the triple negative group.
      No factor predicted mid-course response within the other groups. Grading and age
      can identify subgroups within the luminal and triple negative patients who have
      an increased benefit from NACT.

PMID- 20697802
TI  - Phase II study evaluating the efficacy and safety of sagopilone (ZK-EPO) in
      patients with metastatic breast cancer that has progressed following
      chemotherapy.
AB  - Sagopilone is a novel, fully synthetic epothilone that has shown promising
      preclinical activity in a range of tumor models, including platinum-resistant
      ovarian cancer and metastatic breast cancer (MBC). This open-label, multicenter,
      Phase II study investigated the efficacy, safety, and tolerability of sagopilone
      administered to patients with MBC. Women with MBC whose previous chemotherapy
      regimen included a taxane and an anthracycline received sagopilone 16 or 22
      mg/m(2) as a 3-h intravenous infusion every 21 days. Efficacy (using modified
      Response Evaluation Criteria in Solid Tumors), safety, and tolerability were
      assessed in this population. A total of 65 patients received sagopilone at either
      16 mg/m(2) (N = 39) or 22 mg/m(2) (N = 26). Patients received a median of two
      cycles of sagopilone. Among the 65 patients who were evaluable for efficacy,
      there were three confirmed tumor responses over both treatment arms; however, the
      primary target of the study was not reached. The main treatment-related adverse
      events were sensory neuropathy (81.5%) and fatigue (44.6%). There were no deaths
      related to the study drug. Sagopilone was moderately tolerated in both treatment
      arms and showed limited activity in heavily pre-treated patients with MBC.

PMID- 20697803
TI  - Pre-surgical study of the biological effects of the selective cyclo-oxygenase-2
      inhibitor celecoxib in patients with primary breast cancer.
AB  - Cyclo-oxygenase 2 (COX-2) is implicated in the regulation of aromatase
      transcription in malignant breast tissue and has been considered as a potential
      target for tissue specific aromatase suppression. We initiated a randomised
      controlled pre-surgical study of celecoxib versus no treatment in women with
      primary breast cancer to determine the effects of COX-2 inhibition on markers of
      biological response. Postmenopausal women (50-80 years of age) with stage I or
      II, primary breast cancer, were randomised 2:1 to receive 400 mg/day celecoxib or
      no treatment for 14 days prior to surgery. A core biopsy was obtained pre- and
      post-treatment. Paired baseline and endpoint biopsies were analysed for Ki67,
      apoptosis, COX-2, CD31, estrogen receptor (ER) and progesterone receptor (PgR).
      Comparisons between the treatment groups were conducted using the Mann-Whitney
      test with a two-sided 5% significance. Of the 25 patients treated, 23 had
      evaluable data and 19 (83%) were ER positive. Overall the geometric mean change
      in Ki67, the primary end point, relative to baseline in the celecoxib arm was 
      16.6% (P = 0.056). The change in the no-treatment group was -8.1% (P = 0.24).
      There was no statistically significant difference in the change between the two
      groups. Celecoxib did not significantly affect apoptosis, COX-2, ER or PgR
      expression. There is only modest evidence for a biological effect of celecoxib in
      primary breast cancer. However, the trend towards a reduction in Ki67 in ER
      positive breast cancer warrants further investigations in a larger cohort of
      patients.

PMID- 20697804
TI  - Estrogen deficiency and bone loss in women with breast cancer.

PMID- 20697805
TI  - Screening RAD51C nucleotide alterations in patients with a family history of
      breast and ovarian cancer.
AB  - It has been reported that one biallelic missense mutation in the RAD51C gene was
      found in a Fanconi anemia-like disorder and six monoallelic pathogenic mutations
      were identified in 480 BRCA1/2 negative breast and ovarian cancer pedigrees but
      not in 620 pedigrees with breast cancer only. Additionally, the RAD51C gene was
      reported to be involved in gene fusion events in the MCF-7 breast cancer cell
      line. We performed complete sequencing and fusion gene breakpoint screening to
      detect deleterious mutations and chromosomal structure change in the RAD51C gene.
      Ninety-two hereditary gynecological cancer patients with a family history of
      breast and ovarian cancer but not carrying BRCA1/2 mutations were studied. In
      addition, 46 breast cancer cell lines were screened for the gene fusion events.
      Ten DNA sequence variants but no deleterious mutations were identified. We did
      not observe the occurrence of the known gene fusion either. We were unable to
      confirm the contribution of the RAD51C gene to hereditary breast and ovarian
      cancer (HBOC) in this relatively small cohort. Nonetheless, larger studies in
      diverse populations to fully investigate the mutation spectrum of the RAD51C gene
      are needed.

PMID- 20697806
TI  - Accumulation of mutations over the entire mitochondrial genome of breast cancer
      cells obtained by tissue microdissection.
AB  - The occurrence of heteroplasmy and mixtures is technically challenging for the
      analysis of mitochondrial DNA. More than that, observed mutations need to be
      carefully interpreted in the light of the phylogeny as mitochondrial DNA is a
      uniparental marker reflecting human evolution. Earlier attempts to explain the
      role of mtDNA in cancerous tissues led to substantial confusion in medical
      genetics mainly due to the presentation of low sequence data quality and
      misinterpretation of mutations representing a particular haplogroup background
      rather than being cancer-specific. The focus of this study is to characterize the
      extent and level of mutations in breast cancer samples obtained by tissue
      microdissection by application of an evaluated full mtDNA genome sequencing
      protocol. We amplified and sequenced the complete mitochondrial genomes of
      microdissected breast cancer cells of 15 patients and compared the results to
      those obtained from paired non-cancerous breast tissue derived from the same
      patients. We observed differences in the heteroplasmic states of substitutions
      between cancerous and normal cells, one of which was affecting a position that
      has been previously reported in lung cancer and another one that has been
      identified in 16 epithelial ovarian tumors, possibly indicating functional
      relevance. In the coding region, we found full transitions in two cancerous
      mitochondrial genomes and 12 heteroplasmic substitutions as compared to the non
      cancerous breast cells. We identified somatic mutations over the entire mtDNA of
      human breast cancer cells potentially impairing the mitochondrial OXPHOS system.

PMID- 20697807
TI  - RERG (Ras-like, oestrogen-regulated, growth-inhibitor) expression in breast
      cancer: a marker of ER-positive luminal-like subtype.
AB  - Global gene expression profiling studies have classified breast cancer into a
      number of distinct biological and molecular classes with clinical relevance. The
      heterogeneous luminal group, which is largely characterised by oestrogen receptor
      (ER) expression, appears to contain distinct subgroups with differing behaviour.
      In this study, we analysed 47,293 gene transcripts in 128 invasive breast
      carcinomas (BC) using Artificial Neural Networks and a cross-validation analysis
      in combination with an ensemble sample classification to identify genes that can
      be used to subclassify ER+ luminal tumours. The results were validated using
      immunohistochemistry on TMAs containing 1,140 invasive breast cancers. Our
      results showed that the RERG gene is one of the highest ranked genes to
      differentiate between ER+ luminal-like and ER- non-luminal cancers based on a 10
      fold external cross-validation analysis with an average classification accuracy
      of 89%. This was confirmed in our protein expression studies that showed RERG
      positive associations with markers of luminal differentiation including ER,
      luminal cytokeratins (CK19, CK18 and CK7/8) and FOXA1 (P = 0.004) and other
      markers of good prognosis in BC including small size, lower histologic grade and
      positive expression of androgen receptor, nuclear BRCA1, FHIT and cell cycle
      inhibitors p27 and p21. RERG expression was inversely associated with the
      proliferation marker MIB1 (P = 0.005) and p53. Strong RERG expression showed an
      association with longer breast cancer specific survival and distant metastasis
      free interval in the whole series as well as in the ER+ luminal group and these
      associations were independent of other prognostic variables. In conclusion, we
      used novel bioinformatics methods to identify candidate genes to characterise ER+
      luminal-like breast cancer. RERG gene is a key marker of the luminal BC class and
      can be used to separate distinct prognostic subgroups.

PMID- 20697808
TI  - Evaluation of mentum deformities of Chironomus spp. (Chironomidae: Diptera)
      larvae using modified toxic score index (MTSI) to assess the environmental stress
      in Juru River Basin, Penang, Malaysia.
AB  - Morphological mentum deformities which represent sublethal effect of exposure to
      different types of pollutants were evaluated in Chironomus spp. larvae inhabiting
      three polluted rivers of Juru River Basin in northwestern peninsular Malaysia.
      Using mentum deformity incidences, the modified toxic score index (MTSI) was
      developed based on Lenat's toxic score index (TSI). The suggested MTSI was
      compared with TSI in terms of its effectiveness to identify different pollutants
      including heavy metals. The MTSI showed stronger relationship to total deformity
      incidence expressed as percentage. Additionally, the multivariate RDA model
      showed higher capability of MTSI to explain the variations in heavy metal
      contents of the river sediments. The MTSI was recommended in bioassessment of
      water and sediment quality using the mentum deformities of Chironomus spp. larvae
      from aquatic ecosystems receiving anthropogenic, agricultural, or industrial
      discharges.

PMID- 20697809
TI  - Natural products as DNA methyltransferase inhibitors: a computer-aided discovery
      approach.
AB  - DNA methyltransferases (DNMTs) represent promising targets for the development of
      unique anticancer drugs. However, all DNMT inhibitors currently in clinical use
      are nonselective cytosine analogs with significant cytotoxic side-effects.
      Several natural products, covering diverse chemical classes, have indicated DNMT
      inhibitory activity, but these effects have yet to be systematically evaluated.
      In this study, we provide experimental data suggesting that two of the most
      prominent natural products associated with DNA methylation inhibition, (-)
      epigallocathechin-3-gallate (EGCG) and curcumin, have little or no
      pharmacologically relevant inhibitory activity. We therefore conducted a virtual
      screen of a large database of natural products with a validated homology model of
      the catalytic domain of DNMT1. The virtual screening focused on a lead-like
      subset of the natural products docked with DNMT1, using three docking programs,
      following a multistep docking approach. Prior to docking, the lead-like subset
      was characterized in terms of chemical space coverage and scaffold content.
      Consensus hits with high predicted docking affinity for DNMT1 by all three
      docking programs were identified. One hit showed DNMT1 inhibitory activity in a
      previous study. The virtual screening hits were located within the biological
      relevant chemical space of drugs, and represent potential unique DNMT inhibitors
      of natural origin. Validation of these virtual screening hits is warranted.

PMID- 20697810
TI  - Efficient production of recombinant IgG by metabolic control and co-expression
      with GLUT5 in a fructose-based medium.
AB  - A fructose-based cell culture is suitable for the process control of protein
      production because of slow sugar consumption rate and low lactate accumulation.
      The fructose transporter, GLUT5, mediates its incorporation into cells and is
      required for the fructose-based culture. In order to produce efficiently
      recombinant IgG by metabolic control and co-expression with GLUT5 in a fructose
      based medium, an IgG and GLUT5 co-expression vector was constructed and
      transfected into the human myeloma derived cell line, SC-01MFP, which produced
      stably recombinant proteins. The cell proliferation in the fructose-based medium
      was improved by the GLUT5 gene transfection. The recombinant IgG production of
      the cells cultured in the fructose-based medium exhibited about two-fold increase
      of that in the glucose-based medium. Flow cytometoric analysis indicated that the
      GLUT5 protein expression level in cell surface was increased in the fructose
      based medium. An exogenous but not endogenous GLUT5 transcription activator
      remarkably raised IgG productivity in the fructose-based medium when compared to
      that in the glucose-based medium, suggesting that exogenous GLUT5 expression may
      be involved in it. The GLUT5 co-expression system may be useful for efficient
      production of recombinant proteins by the fructose-based cell culture.

PMID- 20697811
TI  - Early acute depletion of lymphocytes in calicivirus-infected adult rabbits.
AB  - Rabbit Haemorrhagic Disease (RHD) is a lethal infection caused by calicivirus
      that kills 90% of the infected adult rabbits within 3 days. The calicivirus
      replicates in the liver and causes a fulminant hepatitis. Most studies on the
      pathology of RHD have been focused on the fulminant liver disease. This may not
      be the only mechanism in the pathogenesis of RHD: calicivirus infection may also
      induce leukopenia in the infected adult rabbits. We show now by flow cytometry
      analysis that the calicivirus induces an early decrease in B and T cells, in both
      spleen and liver. The depletion of B and T cells was associated with apoptosis
      labelled by annexin V. These changes occurred in rabbits before they showed
      enzymatic evidence of liver damage and persisted after liver transaminase values
      were very high. We conclude that depletion of lymphocytes caused by the
      calicivirus infection precedes or attends liver damage. The relative contribution
      of this lymphocyte depletion for the pathogenesis of the fatal calicivirus
      infection of rabbits remains to be investigated.

PMID- 20697812
TI  - Tumor extent in radical prostatectomy specimens: is it an independent prognostic
      factor for biochemical (PSA) progression following surgery?
AB  - PURPOSE: The tumor volume or extent measurement in radical prostatectomy (RP)
      specimens is time-consuming and technically difficult. We aimed at studying the
      independent prognostic value of tumor extent for biochemical progression-free
      following RP once it is controversial. METHODS: This retrospective study was
      based on 305 consecutive patients submitted to RP. In whole-mount and totally
      embedded surgical specimens, tumor extent was evaluated with a point-count semi
      quantitative method and correlated to several clinical and pathological
      variables. Biochemical progression was defined as PSA >= 0.2 ng/ml; time to
      progression-free outcome was studied using the Kaplan-Meier product-limit
      analysis and univariate and multivariate analyses using the Cox stepwise logistic
      regression. RESULTS: More extensive tumors showed significantly higher
      preoperative PSA (P < 0.01), higher clinical stage (P = 0.03), higher positive
      surgical margins (P < 0.01), higher pathological stage (P < 0.01), and higher
      Gleason score on needle biopsies (P < 0.01) and on surgical specimens (P < 0.01).
      On univariate analysis, biochemical progression correlated with tumor extension
      (P < 0.01), preoperative PSA (P < 0.01), Gleason score on needle biopsies (P =
      0.02) and on surgical specimens (P < 0.01), positive surgical margins (P = 0.01),
      and pathological stage (P = 0.01). There was no difference related to time of
      biochemical recurrence comparing less extensive with more extensive tumors (P =
      0.20). In multivariate analysis, tumor extent was not predictive of biochemical
      progression combined to any one of the variables studied (P > 0.05). CONCLUSIONS:
      Tumor extent did not provide in our study additional predictive information for
      biochemical progression following RP beyond preoperative PSA, Gleason score,
      positive surgical margins, and pathological stage.

PMID- 20697813
TI  - Moving against frailty: does physical activity matter?
AB  - Frailty is a common condition in older persons and has been described as a
      geriatric syndrome resulting from age-related cumulative declines across multiple
      physiologic systems, with impaired homeostatic reserve and a reduced capacity of
      the organism to resist stress. Therefore, frailty is considered as a state of
      high vulnerability for adverse health outcomes, such as disability, falls,
      hospitalization, institutionalization, and mortality. Regular physical activity
      has been shown to protect against diverse components of the frailty syndrome in
      men and women of all ages and frailty is not a contra-indication to physical
      activity, rather it may be one of the most important reasons to prescribe
      physical exercise. It has been recognized that physical activity can have an
      impact on different components of the frailty syndrome. This review will address
      the role of physical activity on the most relevant components of frailty
      syndrome, with specific reference to: (i) sarcopenia, as a condition which
      frequently overlaps with frailty; (ii) functional impairment, considering the
      role of physical inactivity as one of the strongest predictors of physical
      disability in elders; (iii) cognitive performance, including evidence on how
      exercise and physical activity decrease the risk of early cognitive decline and
      poor cognition in late life; and (iv) depression by reviewing the effect of
      exercise on improving mood and increasing positive well-being.

PMID- 20697815
TI  - Abstracts of the 9th European Workshop on Astrobiology. Brussels, Belgium.
      October 12-14, 2009.

PMID- 20697814
TI  - Polymersomes containing iron sulfide (FeS) as primordial cell model : for the
      investigation of energy providing redox reactions.
AB  - According to Wachtershauser's "Iron-Sulfur-World" one major requirement for the
      development of life on the prebiotic Earth is compartmentalization. Vesicles
      spontaneously formed from amphiphilic components containing a specific set of
      molecules including sulfide minerals may have lead to the first autotrophic
      prebiotic units. The iron sulfide minerals may have been formed by geological
      conversions in the environment of deep-sea volcanos (black smokers), which can be
      observed even today. Wachtershauser postulated the evolution of chemical pathways
      as fundamentals of the origin of life on earth. In contrast to the classical
      Miller-Urey experiment, depending on external energy sources, the "Iron-Sulfur
      World" is based on the catalytic and energy reproducing redox system FeS+H2S-
      >FeS2+H2. The energy release out of this redox reaction (?RG degrees =-38 kJ/mol,
      pH 0) could be the cause for the subsequent synthesis of complex organic
      molecules and the precondition for the development of more complex units similar
      to cells known today. Here we show the possibility for precipitating iron sulfide
      inside vesicles composed of amphiphilic block-copolymers as a model system for a
      first prebiotic unit. Our findings could be an indication for a chemoautotrophic
      FeS based origin of life.

PMID- 20697816
TI  - Bioethical issues and health care chaplaincy in aotearoa New Zealand.
AB  - This paper summarizes survey and interview results from a cross-sectional study
      of New Zealand health care chaplaincy personnel concerning their involvement in
      multiple bioethical issues encountered by patients, families and clinical staff
      within the health care context. Some implications of this study concerning health
      care chaplaincy, ecclesiastical institutions, health care institutions and
      government responsibilities are discussed and recommendations presented.

PMID- 20697817
TI  - Quantification of day-to-day variability in growth hormone levels in acromegaly.
AB  - Growth hormone (GH) measurements are routinely used for important treatment
      decisions in patients with acromegaly, yet their reliability is affected by
      numerous factors including assay precision and variability, sampling intensity,
      and hormone pulsatility. The day-to-day variation in GH in acromegaly has not
      been studied. This study quantified the magnitude of day-to-day GH variability in
      patients with acromegaly by performing an analysis of previously obtained plasma
      GH profiles. The analysis was performed at the Michigan Clinical Research Unit at
      the University of Michigan. A total of nine 48 h Q10 min GH profiles obtained in
      nine patients with active acromegaly were examined. The study was planned after
      data collection and analysis was conducted using Altman-Bland methods. Day 1 vs.
      Day 2 values were examined. 95% confidence intervals of the D2 vs. D1 ratios were
      calculated on all individual subject data as well as on a single 0800 h GH sample
      and composite mean data for 2-, 5-, 9-, and 24-h sampling protocols. Confidence
      interval range was 0.66-1.50 for the 0800 h sample and was similar for all
      sampling protocols except somewhat more narrow for the 24-h sampling (0.75-1.32).
      Daily variations in GH levels introduce an additional confounding element when
      using a single GH level or even daily GH curves to assess a patient's GH milieu.
      It may have an impact on result interpretation and subsequent treatment decisions
      especially when GH results are considered borderline.

PMID- 20697818
TI  - Cardiac effects of 3 months treatment of acromegaly evaluated by magnetic
      resonance imaging and B-type natriuretic peptides.
AB  - Long-term treatment of acromegaly prevents aggravation and reverses associated
      heart disease. A previous study has shown a temporary increase in serum levels of
      the N-terminal fraction of pro B-type natriuretic peptide (NT-proBNP) suggesting
      an initial decline in cardiac function when treatment of acromegaly is initiated.
      This was a three months prospective study investigating short-term cardiac
      effects of treatment in acromegalic patients. Cardiac function was evaluated by
      the gold standard method cardiac magnetic resonance imaging (CMRI) and
      circulating levels of B-type natriuretic peptides (BNP and NT-proBNP). CMRI was
      performed at baseline and after 3 months of treatment. Levels of IGF-I, BNP and
      NT-proBNP were measured after 0, 1, 2 and 3 months. Eight patients (5 males and 3
      females, mean age 53 +/- 12 years (range 30-70)) and 8 matched healthy control
      subjects were included. Median IGF-I Z-score decreased from 4.5 (range 2.5-6.4)
      to 2.3 (-0.1 to 3.3). At baseline the patients had increased left ventricle mass
      index (LVMI) compared to control subjects (DeltaLVMI 35 g/m(2) (95% CI 8-63
      g/m(2), P = 0.016). After 3 months of treatment there was an increase in end
      diastolic volume index EDVI (DeltaEDVI 9 mL/m(2) (95% CI 3-14), P = 0.007) and an
      increase in levels of BNP (median (ranges) 7 (0.58-286) vs. 20 (1-489) pg/mL, P =
      0.033) and of NT-proBNP (63 (20-1004) vs. 80 (20-3391) pg/mL, P = 0.027).
      Assessed by the highly sensitive and precise CMRI method, 3 months treatment of
      acromegaly resulted in an increase in EDVI, and increased levels of BNP and NT
      proBNP suggesting an initial decrease in cardiac function.

PMID- 20697819
TI  - Licofelone attenuates MPTP-induced neuronal toxicity: behavioral, biochemical and
      cellular evidence.
AB  - Neuroinflammation and oxidative stress play critical role in the pathophysiology
      of neurodegenerative diseases including Parkinson's disease (PD). Recent reports
      indicate the beneficial effect of anti-inflammatory drugs in attenuating the
      progression of PD. Therefore, the present study is aimed to evaluate the possible
      role of licofelone, a dual COX/LOX-inhibitor against MPTP-induced neurotoxicity
      in mice. Administration of MPTP (40 mg/kg in divided doses of four injections of
      10 mg/kg, i.p. each at 1 h interval) significantly impaired locomotor activity
      and induced catatonia, oxidative damage (elevated levels of lipid peroxidation,
      superoxide anion and nitrite, and decreased levels of non-protein thiols) as
      compared with vehicle-treated animals. Biochemical studies revealed significant
      alterations in mitochondrial enzyme complex activities (decreased complex-I
      activity and mitochondrial viability) and increased levels of caspase-3 and NF
      kappaB/p65 as compared to vehicle treated group. Licofelone (2.5, 5 or 10
      mg/kg/day, p.o.) treatment for 7 days significantly improved locomotor activity,
      attenuated the severity of catatonia, oxidative damage and restored mitochondrial
      enzyme complex activity as compared to MPTP-treated group. Licofelone treatment
      also attenuated the expression of apoptotic factor (caspase-3) and transcription
      factor (NF-kappaB/p65) as compared to MPTP-treated group. The findings of the
      present study suggest that licofelone (dual inhibitor of COX and LOX) represents
      a new class of anti-inflammatory agent which may provide a novel therapeutic
      alternative for the treatment and management of PD.

PMID- 20697820
TI  - Aesthetics in breast conserving therapy: do objectively measured results match
      patients' evaluations?
AB  - BACKGROUND: To analyze the relationship of objective and subjective evaluation
      tools of breast aesthetics, we compare the results of the BCCT.core (breast
      cancer conservative treatment.cosmetic results) software, a semiautomated
      objective symmetry evaluation tool, with those of the Aesthetic Status of the
      BCTOS (Breast Cancer Treatment Outcome Scale) patient questionnaire. MATERIALS
      AND METHODS: We included 128 patients with one-sided, primary breast cancer,
      treated conservatively in a prospective, exploratory study in order to assess the
      inter-rater reliability of the BCCT.core and the agreement between the BCCT.core
      and the BCTOS preoperatively, shortly and 1 year after surgery. Therefore, we use
      agreement rates, multiple (mk), and weighted (wk) kappa coefficients as
      statistical methods. Furthermore, we analyzed patient-, tumor-, and therapy
      related variables as possible covariates to explain agreement. RESULTS: The inter
      rater reliability for the semiautomated BCCT.core is very good with agreement
      rates up to 84% (mk = 0.80). The agreement rates of the BCCT.core and the BCTOS
      Aesthetic Status range between 35 and 44% subject to the different times of
      assessment (wk = 0.34 at best). Moreover, the patients judge their aesthetic
      outcome more positively than the software. None of the considered patient-, tumor
      , and therapy-related covariates turned out to explain agreement. CONCLUSION: The
      BCCT.core is a reliable instrument that shows fair agreement with patient's
      perspective.

PMID- 20697821
TI  - Clinical outcome of tertiary surgical cytoreduction in patients with recurrent
      epithelial ovarian cancer.
AB  - BACKGROUND: The value of tertiary cytoreductive surgery (TCS) on overall survival
      (OS) of patients with relapsed epithelial ovarian cancer (ROC) is not well
      defined. Aim of the present study was to evaluate the operative and clinical
      outcome after TCS. METHODS: We systematically evaluated all consecutive patients
      undergoing TCS. Tumor dissemination pattern, operative morbidity, residual tumor,
      and survival are described based on a validated intraoperative documentation
      tool. Predictors of survival and complete tumor resection are analyzed with Cox
      regression or logistic regression models. RESULTS: Between October 2000 and
      December 2008, 135 patients (median age, 51 years; range, 22-80 years) of mainly
      initial FIGO stage >= III (106 patients, 78.5%) were evaluated. In 53 patients
      (39.3%) a complete tumor-resection was obtained. The 1-month operative mortality
      was 6%. During a median follow-up period of 9.6 months (range, 0.1-75 months), 78
      patients (57.8%) died, while 52 patients (38.5%) experienced a further relapse.
      Median OS was 19.1 months for the total collective (95% confidence interval [95%
      CI], 14.84-23.35). Median OS was 37.8 months (95% CI, 12.7-62.7) for patients
      without residual tumor; versus 19.0 months (95% CI, 9.8-28.2) for residual tumor
      <= 1 cm and 6.9 months (95% CI, 3.05-10.7) for residual tumor > 1 cm (P < .001).
      The presence of peritoneal carcinomatosis did not seem to significantly affect
      OS. Complete tumor resection was identified as the strongest predictor of OS.
      Other independent predictors of OS were interval to primary diagnosis >= 3 years
      (hazard ratio [HR], 0.28; 95% CI, 0.14-0.59) and serous papillary histology (HR,
      0.23; 95% CI, 0.09-0.56). A total of 42 patients (31.1%) presented at least 1
      major complication. Multivariate analysis identified tumor involvement of the
      middle abdomen and peritoneal carcinomatosis as independent predictors of
      complete tumor resection. CONCLUSIONS: Postoperative tumor residual disease
      remains the strongest predictor of survival even in TCS setting. To identify the
      optimal candidates for TCS, the predictive value of ascites and peritoneal
      carcinomatosis should be confirmed by future prospective trials.

PMID- 20697822
TI  - Impact of circumferential resection margin distance on locoregional recurrence
      and survival after chemoradiotherapy in esophageal squamous cell carcinoma.
AB  - BACKGROUND: Close circumferential resection margin (CRM) is an established
      predictor for locoregional recurrence (LR) in rectal cancer but remains
      controversial in esophageal malignancy. As yet, little is known about the
      significance of CRM after chemoradiotherapy (CRT), especially in squamous cell
      carcinoma (SCC). This study investigated the relationship between CRM distance
      and recurrence after neoadjuvant CRT in esophageal SCC patients. METHODS: Between
      1997 and 2005, esophageal SCC patients who underwent surgery after neoadjuvant
      CRT and with pathology stage T3N0M0 and T3N1M0 (metastatic lymph nodes <2) were
      selected. CRM distance was reassessed and divided into three groups (group 1: CRM
      >1 mm, group 2: uninvolved CRM but <1 mm, group 3: CRM involved). RESULTS: The
      cohort comprised 145 male and 6 female patients with mean age of 57 years. There
      were 74, 51, and 26 patients in group 1, 2, and 3, respectively. With median
      follow-up period of 50 months, LR developed in 30.5% of patients. Both group 2
      and group 3 had significantly higher LR than group 1 (37 and 42% vs. 21%, P <
      0.05). Meanwhile, mean time from operation to recurrence was also significantly
      shorter in group 2 and group 3 than in group 1 (267 and 269 days versus 402 days,
      P < 0.05). Five-year disease-specific survival (DSS) was highest in group 1
      (40%). Despite the similarity in LR, 5-year DSS significantly differed between
      group 2 and group 3 (22 vs. 7%, P < 0.05). The higher rate of distant recurrence
      (DR) and concomitant LR + DR in group 3 accounted for the survival difference.
      CONCLUSION: In ypT3 esophageal SCC patients, CRM distance provides useful
      information for risk stratification in cancer recurrence and survival.

PMID- 20697823
TI  - Supratentorial glioblastoma multiforme: the role of surgical resection versus
      biopsy among older patients.
AB  - BACKGROUND: The peak incidence of glioblastoma multiforme (GBM) occurs in those
      aged 65 years and older. However, studies on this patient group remain limited.
      The goal of this study is to evaluate the efficacy of surgery versus biopsy for
      older patients with these lesions. METHODS: 133 and 72 consecutive patients aged
      65 years and older who underwent surgery and needle biopsy for intracranial
      primary (de novo) GBM between 1997 and 2007 were retrospectively reviewed. Among
      these patients, 40 who underwent surgical resection were matched with 40 who
      underwent needle biopsy alone for factors consistently shown to be associated
      with survival [age, Karnofsky Performance Scale (KPS) indexing, eloquent
      involvement, radiation, temozolomide]. Survival was expressed as estimated Kaplan
      Meier plots, and log-rank analysis was used to compare survival curves. RESULTS:
      Mean +/- standard deviation age was 73 +/- 5 years, and median survival was 4.9
      months. There were no significant differences in perioperative outcomes among
      patients who underwent surgical resection versus needle biopsy. Patients who
      underwent resection had median survival of 5.7 months as compared with 4.0 months
      for patients who underwent needle biopsy (P = 0.02). Likewise, for patients aged
      70 years and older, median survival was 4.5 months for 26 patients who underwent
      surgical resection as compared with 3.0 months for 26 patients who underwent
      needle biopsy (P = 0.03). CONCLUSION: This study demonstrates that older patients
      tolerate aggressive surgery without increased surgery-related morbidity and have
      prolonged survival as compared with similar patients undergoing needle biopsy.
      These findings may help guide treatment decisions for patients, their families,
      and their physicians.

PMID- 20697825
TI  - Nachdruck: : Die beiden Aspekte der wissenschaftlichen Revolution des 17.
      Jahrhunderts und die Gegenwart.

PMID- 20697824
TI  - Systematic review on the efficacy of multimodal treatment of sarcomatosis with
      cytoreduction and intraperitoneal chemotherapy.
AB  - BACKGROUND: Peritoneal sarcomatosis carries a dismal prognosis with median
      survival of 12 months and no 5-year survivors. The treatment for sarcomatosis has
      mostly been chemotherapy and surgery for palliation. Recently, cytoreduction
      (CRS) and intraperitoneal chemotherapy (IPC) has been tried as an alternative for
      improving regional control and survival, but the efficacy of this combined
      treatment is difficult to determine. The objective of this review is to evaluate
      all available evidence to determine the efficacy of this treatment modality.
      MATERIALS AND METHODS: Searches for studies published in peer-reviewed journals
      before October 2010 were carried out on 3 databases. The reference lists of all
      identified articles were reviewed for further relevant studies. Relevant studies
      were then evaluated by 3 investigators, and the quality of each study was
      assessed. Studies that met an established criterion were reviewed for clinical
      effectiveness with a tabulation of all results. RESULTS: Eight prospective and
      one randomized trial were available representing 240 patients treated with CRS
      and IPC. The median disease-free survival ranged from 2.3 to 22 months, median
      survival ranged from 5.5 to 39.6 months, and the 5-year survival ranged from 7%
      to 65%. The surgical morbidity varied from 9% to 44% and the mortality from 0% to
      11%. CONCLUSIONS: Based on the available data, this treatment approach is
      currently not recommended in the treatment of sarcomatosis except in experienced
      centers, in well-selected patients and as part of an experimental protocol.

PMID- 20697829
TI  - fMRI assessment of upper extremity related brain activation with an MRI
      compatible manipulandum.
AB  - PURPOSE: Longitudinal studies to evaluate the effect of rehabilitative therapies
      require an objective, reproducible and quantitative means for testing function in
      vivo. An fMRI assessment tool for upper extremity related brain activation using
      an MRI-compatible manipulandum was developed and tested for use in
      neurorehabilitation research. METHODS: Fifteen healthy, right-handed subjects
      participated in two fMRI sessions, which were three to four weeks apart. A block
      design paradigm, composed of three conditions of subject-passive movement,
      subject-active movement and rest, was employed for the fMRI recordings. During
      the rest condition, subjects simply held the device handle without applying any
      force or movement. The same type of auditory and visual instructions were given
      in all the three conditions, guiding the subjects to perform the motor tasks
      interactively with the MRI-compatible arm manipulandum. The tasks were controlled
      across the fMRI sessions. The subjects' brain activation was recorded by fMRI,
      and their behavioral performance was recorded by the manipulandum. The brain
      network activated by the subjects' interaction with the manipulandum was
      identified, and the reproducibility and reliability of the obtained activation
      were determined. RESULTS: All subjects completed the trial protocol. Two subjects
      were excluded from analysis due to head motion artifacts. All passive movements
      were performed well. Four out of the total 780 active movements were missed by
      two subjects. Brain activation was found in the contralateral sensorimotor
      cortex, secondary somatosensory cortex and non-primary motor cortex as well as in
      subcortical areas in the thalamus, basal ganglia and the cerebellum. These
      activations were consistent across the two fMRI sessions. CONCLUSION: The MRI
      compatible manipulandum elicited robust and reproducible brain activations in
      healthy subjects during the subject-active and subject-passive upper extremity
      motor tasks with a block design paradigm. This system is promising for many
      applications in neurorehabilitation research and may be useful for longitudinal
      studies.

PMID- 20697826
TI  - [Stress, cortisone and homeostasis. Adrenal cortex hormones and physiological
      equilibrium, 1936-1960].
AB  - This article investigates the emergence of the concept of stress in the 1930s and
      outlines its changing disciplinary and conceptual frames up until 1960.
      Originally stress was a physiological concept applied to the hormonal regulation
      of the body under stressful conditions. Correlated closely with chemical research
      into corticosteroids for more than a decade, the stress concept finally became a
      topic in cognitive psychology. One reason for this shift of the concept to
      another discipline was the fact that the hormones previously linked to the stress
      concept were successfully transferred from laboratory to medical practice and
      adopted by disciplines such as rheumatology and dermatology. Thus the stress
      concept was dissociated from its hormonal context and became a handy formula that
      allowed postindustrial society to conceive of stress as a matter of individual
      concern. From a physiological phenomenon stress turned into an object of
      psychological discourse and individual coping strategies.

PMID- 20697830
TI  - Fast and flexible distance measures for treatment planning.
AB  - PURPOSE: Distance measures are required for diagnoses, therapy decision and
      documentation. With today's high-resolution CT and MR imaging techniques, high-
      quality images have become possible. Yet, manual measurement can be tedious. We
      present a method for automatically determining different distance-based measures
      on segmented anatomic structures, like shortest distances, diameters, and wall
      thicknesses. METHODS: Our method is inspired from computational geometry and
      based on a surface mesh representation. The computation takes all primitives
      (points, edges, faces) into account and organizes them efficiently in a spatial
      tree structure. We followed the generic design paradigm in order to achieve
      maximum flexibility. RESULTS: The generic approach allows for a variety of
      intervention-relevant distance measures to be computed, using only a single type
      of data structure. For shortest distance, our approach in empirical tests turned
      out to be more efficient than previous methods from medical application
      literature. Besides the numerical value, also its defining geometric primitives
      are determined. CONCLUSIONS: The presented technique is both, fast and flexible.
      It can be used to interactively derive automatic distance measures for arbitrary
      mesh-based segmentations. Due to the geometrically exact measurements, it is
      possible to reliably estimate safety margins, assess possible infiltrations and
      other clinically relevant measures. To exploit this benefit, the method requires
      precise segmentations as input data.

PMID- 20697831
TI  - The in vitro effects of 2-methoxyestradiol-bis-sulphamate on cell numbers,
      membrane integrity and cell morphology, and the possible induction of apoptosis
      and autophagy in a non-tumorigenic breast epithelial cell line.
AB  - 2-methoxyestradiol (2ME2) exerts estrogen receptor-independent anti
      proliferative, anti-angiogenic and anti-tumor activity in vitro and in vivo. Due
      to its low bioavailability and rapid metabolic degradation, several analogues
      have been developed in recent years. 2-methoxyestradiol-bis-sulphamate (2
      MeOE2bisMATE) is a bis-sulphamoylated derivative of 2ME2 with anti-proliferative
      activity. The aim of this study was to investigate cell signaling events induced
      by 2-MeOE2bisMATE in a non-tumorigenic cell line (MCF-12A) by analysing its
      influence on cell number, morphology and membrane integrity, and the possible
      induction of apoptosis and autophagy. Dose- and time-dependent studies revealed
      that 48 h exposure to 2-MeOE2bisMATE (0.4 MUM) resulted in a decrease in cell
      numbers to 79%. A slight increase in the level of lactate dehydrogenase
      production was observed in the 2-MeOE2bisMATE-treated cells. Morphological
      studies revealed an increase in the number of cells in metaphase. Hallmarks of
      apoptosis were also found, namely nuclear fragmentation and apoptotic bodies. In
      addition, increased lysosomal staining was observed via fluorescent microscopy,
      suggesting the induction of another type of cell death, namely autophagy. Since 2
      MeOE2bisMATE is regarded as a potential anti-cancer agent, it is also imperative
      to investigate the susceptibility of non-tumorigenic cells to its influence. The
      data generated from this study contributes to the understanding of the action
      that 2-MeOE2bisMATE exerts on the non-tumorigenic MCF-12A breast epithelial cell
      line.

PMID- 20697832
TI  - Preservation of replaced or accessory right hepatic artery during
      pancreaticoduodenectomy for adenocarcinoma: impact on margin status and survival.
AB  - AIM: The aim of the study was to determine the impact of replaced or accessory
      right hepatic artery (RARHA) during pancreaticoduodenectomy (PD) for pancreatic
      adenocarcinoma (PA). METHODS: Four hundred seventy-one consecutive patients
      underwent PD for PA at the two institutions; 47 patients (10%) had RARHA: 16
      patients (neoRARHA group) received neoadjuvant chemoradiation, and 31 patients
      did not receive preoperative treatment (RARHA group). Thirty-one matched patients
      without RARHA comprised our control group. RESULTS: RARHA was preserved in 44
      patients; three patients with involved RARHA had reconstruction (n = 2) or
      ligation (n = 1). Patients with R1 resection (n = 8) had tumor size >=3 cm.
      Patients in the neoRARHA group had identical positive margin rate when compared
      with patients in RARHA group (p = 0.6). No difference was noted in median or 3
      year overall survival times between RARHA group and control group. Two patients
      in RARHA group with involved RARHA died of disease progression after 6 and 12
      months of follow-up. One patient in neoRARHA group with involved RARHA was still
      alive without recurrence after 28 months' follow-up. CONCLUSIONS: Pathologic
      findings did not show increased positive margins despite preservation of RARHA.
      In contrast, patients with frank RARHA involvement seemed to have poor survival.
      Thus, patients with suspicion of involved RARHA should be considered for
      neoadjuvant chemoradiation.

PMID- 20697833
TI  - Element distribution in visual system, the optic chiasma, lateral geniculate
      body, and superior colliculus.
AB  - To elucidate compositional changes of the visual system with aging, the authors
      investigated age-related changes of elements in the optic chiasma, lateral
      geniculate body, and superior colliculus, relationships among their elements,
      relationships among their brain regions from a viewpoint of elements, and gender
      differences in their elements by direct chemical analysis. After ordinary
      dissection at Nara Medical University was finished, the optic chiasmas, lateral
      geniculate bodies, and superior colliculi were resected from identical cerebra of
      the subjects. The subjects consisted of 14 men and 10 women, ranging in age from
      75 to 96 years (average age = 85.6 +/- 5.9 years). After ashing with nitric acid
      and perchloric acid, element contents were determined by inductively coupled
      plasma-atomic emission spectrometry. As the result, the average content of P was
      significantly higher in the optic chiasma and superior colliculus compared with
      the lateral geniculate body. Regarding age-related changes of elements, no
      significant changes with aging were found in seven elements of the optic chiasma,
      lateral geniculate body, and superior colliculus in the subjects more than 75
      years of age. The findings that with regard to the relationships among elements,
      there were extremely significant direct correlations between Ca and Zn contents
      and significant inverse correlations between Mg and Na contents were obtained in
      common in all of the optic chiasma, lateral geniculate body, and superior
      colliculus. It was examined whether there were significant correlations among the
      optic chiasma, lateral geniculate body, and superior colliculus in the seven
      elements and the following results were obtained: There were significant direct
      correlations between the optic chiasma and lateral geniculate body in both the P
      and Mg contents; there was a significant direct correlation between the optic
      chiasma and superior colliculus in the Fe content; and a significant direct
      correlation was found between the lateral geniculate body and superior colliculus
      in the Mg content. Regarding the gender differences in elements, it was found
      that both the Ca and Zn contents of the lateral geniculate body were
      significantly higher in women than in men.

PMID- 20697834
TI  - A- and B-chromosome pairing and recombination in male meiosis of the silver fox
      (Vulpes vulpes L., 1758, Carnivora, Canidae).
AB  - We examined A- and B-chromosome pairing and recombination in 12 males from the
      farm-bred population of the silver fox (2n = 34 + 0-10 Bs) by means of electron
      and immunofluorescent microscopy. To detect recombination at A and B chromosomes,
      we used immunolocalisation of MLH1, a mismatch repair protein of mature
      recombination nodules, at synaptonemal complexes. The mean total number of MLH1
      foci at A-autosomes was 29.6 foci per cell. The XY bivalent had one MLH1 focus at
      the pairing region. Total recombination length of the male fox genome map was
      estimated as 1,530 centimorgans. We detected single MLH1 foci at 61% of linear
      synaptic configurations involving B chromosomes. The distribution of the foci
      along B- and A-bivalents was the same. This may be considered as a first
      molecular evidence that meiotic recombination does occur in mammalian B
      chromosomes. There was no correlation between the number of synaptic
      configurations involving B chromosomes per cell and the recombination rate of the
      A-genome.

PMID- 20697837
TI  - Cardiac rupture after intravenous t-PA administration in acute ischemic stroke.
AB  - BACKGROUND: Ventricular free wall rupture is a fatal complication of myocardial
      infarction (MI). Although described in MI patients who receive thrombolytic
      therapy, this complication is not well known in ischemic stroke patients who
      receive intravenous (IV) t-PA. METHODS: Case report. RESULTS: We present a 93
      year-old woman with an acute onset of a right middle cerebral artery syndrome in
      the setting of subacute MI. IV t-PA was administered and she subsequently
      developed asystolic arrest and died. Autopsy showed subacute MI, hemopericardium,
      and rupture of the left ventricle. CONCLUSIONS: This case illustrates a fatal
      cardiac complication of IV thrombolytic therapy for stroke. The speculated
      mechanism is hemorrhage into the infarcted myocardium.

PMID- 20697836
TI  - Intensive versus conventional insulin therapy in critically ill neurologic
      patients.
AB  - BACKGROUND: Previous studies of glycemic control in non-neurologic ICU patients
      have shown conflicting results. The purpose was to investigate whether intensive
      insulin therapy (IIT) to keep blood glucose levels from 80 to 110 mg/dl or
      conventional treatment to keep levels less than 151 mg/dl was associated with a
      reduction of mortality and improved functional outcome in critically ill
      neurologic patients. METHODS: Within 24 h of ICU admission, mechanically
      ventilated adult neurologic patients were enrolled after written informed consent
      and randomized to intensive or conventional control of blood glucose levels with
      insulin. Primary outcome measure was death within 3 months. Secondary outcome
      measures included 90-day modified Rankin scale (mRS) score, ICU, and hospital
      LOS. RESULTS: 81 patients were enrolled. The proportion of deaths was higher
      among IIT patients but this was not statistically significant (36 vs. 25%, P =
      0.34). When good versus poor outcome at 3 months was dichotomized to mRS score 0
      2 versus 3-6, respectively, there was no difference in outcome between the two
      groups (76.2 vs. 75% had a poor 3-month outcome, P = 1.0). There was also no
      difference in ICU or hospital LOS. Hypoglycemia (<60 mg/dl) and severe
      hypoglycemia (<40 mg/dl) were more common in the intensive arm (48 vs. 11%, P =
      0.0006; and 4 vs. 0%, P = 0.5, respectively). CONCLUSION: There was no benefit to
      IIT in this small critically ill neurologic population. This is the first
      glycemic control study to specifically examine both critically ill stroke and
      traumatic brain injury (TBI) patients and functional outcome. Given these
      results, IIT cannot be recommended over conventional control.

PMID- 20697839
TI  - Bilateral ocular involvement as a presentation of Waldenstrom's
      macroglobulinemia.
AB  - We describe a 54 years old female with Waldenstrom's macroglobulinemia who
      presented with a bilateral ocular involvement. Ophthalmic involvement in
      Waldenstrom's macroglobulinemia is very rare. In addition, to our knowledge,
      there are only a few reports in the literature in which a primary diagnosis was
      made on the basis of ocular involvement. Diagnosis of malignancy in our case was
      established on the basis of the presence of small lymphocytes in fine-needle
      aspiration cytology from the orbital mass and typical bone marrow aspiration
      immunophenotype for Waldenstrom's macroglobulinemia.

PMID- 20697838
TI  - Reproductive immunology: a focus on the role of female sex hormones and other
      gender-related factors.
AB  - Reproductive immunology has attracted the attention of researchers interested in
      fertility and pregnancy as well as those interested in immunity and autoimmunity.
      Over the past couple of decades, a wealth of data on the immune-reproductive
      interactions has been generated. This issue of the Journal will examine several
      topics including the role of immune factors in the induction of anti-Ro antibody
      mediated autoimmunity in neonates and the immunological effects of gender and sex
      hormones. The possible implications of the research reviewed here for the
      development of novel therapeutic approaches are also addressed.

PMID- 20697840
TI  - ATRA and anthracycline-based chemotherapy in the treatment of childhood acute
      promyelocytic leukemia (APL): A 10-year experience in Tunisia.
AB  - Reports on childhood APL from developing countries are scarce. We treated 65 APL
      with two consecutive trials combining ATRA and chemotherapy. Twenty (30.7%) were
      aged less than 20 years including 11 girls and 9 boys, with a median age of 12
      years. Fever at presentation (P=0.002) and variant APL (P=0.044) were more
      frequent in children, while there were no significant difference between children
      and adults for WBC count, Sanz's score distribution and additional cytogenetic
      abnormalities. The CR rate was 95% (19/20) in children and 80% (36/45) in adults
      (P=0.13). Differentiation syndrome (DS) was less often observed in children
      (1/20) than in adults (13/45) (P=0.031). Two children relapsed and died during
      salvage therapy, and 2 died in CR from infection and from cardiac failure
      attributed to anthracyclines, while other children remained alive in CR. With a
      median follow-up of 4 years, 4-year EFS was 75% in children and 71.1% in adults
      (P=0.57), while 4-year OS was 75% in children vs. 73.3% in adults (P=0.72). Our
      results suggest that, even in the absence of optimal socio-economic condition,
      ATRA combined with anthracycline-based chemotherapy gives adequate results in
      childhood APL, as in adults.

PMID- 20697841
TI  - Pro-apoptotic protein BIM in apoptosis of glucocorticoid-sensitive and -resistant
      acute lymphoblastic leukemia CEM cells.
AB  - Although glucocorticoids (GCs) have been used to treat acute lymphoblast leukemia
      (ALL) for decades, the mechanisms of GC sensitivity and resistance in ALL cells
      are poorly understood. This study investigated the role and mechanisms of pro
      apoptotic protein BIM in apoptosis of GC-sensitive and- resistant ALL cells. The
      dramatic apoptosis was observed in GC-sensitive CEM-C7 cells after incubated with
      DEX for 48 h, while not in GC-resistant CEM-C1 cells. The significant up
      regulation of BIM in CEM-C7 cells induced by DEX was also observed, but no up
      regulation of BIM was detected in DEX-induced CEM-C1 cells. When treated with DEX
      plus RU486, a glucocorticoid receptor blocker, the apoptosis and BIM expression
      of CEM-C7 cells were canceled. P38MAPK-blocking pharmacon SB203580 also
      significantly inhibited the up-regulation of BIM in CEM-C7 cells. These suggested
      that the absence of BIM up-regulation is one of the important mechanisms of GC
      resistance, GC-GR conjugation is indispensible in both GC-induced apoptosis and
      up-regulation of BIM, and p38 MAPK signal pathway is also involved in this
      process.

PMID- 20697842
TI  - Long-term response with everolimus for metastatic renal cell carcinoma refractory
      to sunitinib.
AB  - A 70-year-old man with metastatic renal cell carcinoma developed progressive
      liver metastases after 8 weeks of treatment with the multitargeted tyrosine
      kinase inhibitor (TKI) sunitinib. He then participated in the phase III placebo
      controlled clinical trial of the oral mammalian target of rapamycin (mTOR)
      inhibitor everolimus, initially randomized to placebo (but had disease
      progression after 3 months) and crossed over to everolimus at time of unblinding.
      The patient had stable disease after 8 weeks (two cycles) of everolimus that was
      maintained until 28 months of therapy, at which time the patient had achieved a
      partial response. This case illustrates the potential for patients with
      metastatic renal cell carcinoma, a malignancy with historically poor prognosis,
      to derive long-term benefit from everolimus when used in a manner consistent with
      its approved indication (after TKI therapy with sunitinib or sorafenib).

PMID- 20697843
TI  - Unexpected death of a young woman: is myocardial bridging significant?--A case
      report and review of literature.
AB  - Myocardial bridging (MB) refers to a congenital condition where a segment of a
      major coronary artery courses within the myocardium for a variable distance, and
      has been reported as an incidental finding in many cases. However, in some
      situations it has been shown to be associated with acute coronary syndromes,
      arrhythmias, myocardial ischemia and sudden death. We present the case of a 26
      year-old Chinese woman with no previous history of disease who died unexpectedly
      in hospital. She had a 'common cold' with its associated symptoms. Autopsy
      revealed the presence of MB of the left anterior descending artery and
      microscopic examination showed associated cardiac lesions such as contraction
      band necrosis and interstitial fibrosis in the region supplied by the embedded
      artery. The coronaries were otherwise patent. Gross and microscopic examination
      of other organs was unremarkable. Toxicological analysis of body fluids and
      stomach content excluded death due to either drug intoxication or known poisonous
      substances. MB could have been responsible for death, but the disparate attitudes
      towards this phenomenon made this assumption open to discussion. We provide the
      case description and a short review of the literature on fatal and near- fatal
      cases involving MB.

PMID- 20697844
TI  - Genetics of menstrual migraine: the epidemiological evidence.
AB  - Approximately one of every three to five women with migraine without aura
      experience migraine attacks in relation to menstruation. The International
      Classification of Headache Disorders, 2nd Edition provides appendix diagnoses for
      pure and menstrually related migraine without aura that need further validation.
      Probands with menstrual migraine might have more affected relatives than probands
      with nonmenstrual migraine. However, precise epidemiological, family, and twin
      data still are lacking.

PMID- 20697845
TI  - Sex hormones and pain: the evidence from functional imaging.
AB  - There is a substantial body of epidemiological and clinical evidence suggesting
      that the sex hormones, particularly estradiol and progesterone, play a role in
      pain. Behavioral studies have not been useful in understanding the relationship
      between sex hormones and pain perception, and certainly have not helped to
      elucidate the mechanisms by which such effects may be mediated. This review aims
      to address the additional insights functional imaging has given us into the role
      of sex hormones in pain. Functional imaging techniques and experimental designs
      are discussed before the literature investigating specific questions relating to
      hormones and pain is reviewed. Finally, we conclude by considering how results of
      studies imaging the influence of sex hormones in related areas such as emotion
      and cognition also may inform our understanding of this complex area.

PMID- 20697846
TI  - Management of menstrual migraine: a review of current abortive and prophylactic
      therapies.
AB  - After menarche, women have an increased prevalence of migraine compared to men.
      There is significant variability in the frequency and severity of migraine
      throughout the menstrual cycle. Women report migraines occur more frequently
      during menses, and that those are more severe than other migraines. This creates
      a unique challenge of effectively treating menstrually related and pure menstrual
      migraines. As with treatment of other migraines, both abortive and prophylactic
      treatment regimens are used. Triptans demonstrate efficacy in the abortive
      management of menstrually related and pure menstrual migraines. For migraines
      that occur primarily during menses or that are particularly resistant to other
      therapies, intermittent prophylactic therapies can be used. Naproxen and
      estrogens have been studied for this use. More recently, triptans have been
      examined and have shown efficacy for intermittent prophylaxis of menstrual
      migraine.

PMID- 20697847
TI  - Marine omega-3 Fatty acids and plaque stabilization.

PMID- 20697848
TI  - Treatment of internet addiction.
AB  - Internet addiction (IA) is a prevalent, highly comorbid, and significantly
      impairing disorder. Although many psychotherapeutic approaches and psychotropic
      medications have been recommended and some of the psychotherapeutic approaches
      and a few pharmacotherapy strategies have been studied, treatment of IA is
      generally in its early stages. This article reviews theoretical descriptions of
      psychotherapy and the effects of psychosocial treatment and pharmacologic
      treatment. We also outline our own treatment model of IA.

PMID- 20697849
TI  - Attention-deficit/hyperactivity disorder in African American youth.
AB  - This article examines attention-deficit/hyperactivity disorder (ADHD) in African
      American youth. Tackling the myths and misinformation surrounding ADHD in the
      African American community can be one of the most difficult issues in mental
      illness circles. There is a lot of conflicting information about how African
      Americans are diagnosed, examined, and treated. This article clarifies some of
      the misconceptions and offers some comprehensibility to the issue of ADHD in
      African American youth. The incidence of ADHD is probably similar in African
      Americans and Caucasians. However, fewer African Americans are diagnosed with and
      treated for ADHD. That reality flies in the face of some perceptions in many
      African American communities. Reasons for this disparity have not been fully
      clarified and are most likely complex and numerous. Some barriers to treatment
      are driven by the beliefs of patients and their families, while others are the
      result of limitations in the health care system. Patient-driven obstacles to care
      include inadequate knowledge of symptoms, treatment, and consequences of
      untreated ADHD and fear of overdiagnosis and misdiagnosis. System-driven
      limitations include a lack of culturally competent health care providers,
      stereotyping or biases, and failure of clinicians to evaluate the child in
      multiple settings before diagnosis.

PMID- 20697850
TI  - What's new in the treatment of cocaine addiction?
AB  - Cocaine dependence continues to be a significant public health problem in the
      United States. The number of regular cocaine users has not declined significantly
      in the United States since 1992. Although counseling remains the treatment of
      choice for cocaine dependence, many cocaine-dependent patients do not respond
      completely to standard drug counseling. Therefore, the development of new and
      more effective treatments for cocaine dependence is a research priority. Progress
      in the understanding of the neurobiology of cocaine dependence has led to the
      discovery of several promising medications that have already shown encouraging
      results in controlled clinical trials. Other promising compounds are just
      becoming available for clinical trials. The use of novel psychosocial techniques
      such as contingency management seems to increase the efficacy of several
      medications used to treat cocaine dependence. New medications and new
      psychosocial techniques are leading to significant improvements in the treatment
      of cocaine dependence.

PMID- 20697851
TI  - Collision tumor of primary laryngeal mucosal melanoma and invasive squamous cell
      carcinoma with IL-17A and CD70 gene over-expression.
AB  - The most common primary malignancy of the larynx is the squamous cell carcinoma
      (SCC). The primary malignant melanoma is quite rare in this location. Less than
      60 cases of laryngeal melanomas have been reported to date. To our knowledge,
      collision primary malignant melanoma and invasive squamous cell carcinoma in the
      vocal cords has not been reported. We report a 53-year-old male patient who was
      diagnosed with a collision tumor of laryngeal melanoma and invasive SCC. Multiple
      Th17 pathway related genes including CTLA-4, IL-17A-F, PLZF, FoxP3, RorgammaT,
      CD27, and CD70 were analyzed by reverse transcriptase-polymerase chain reaction
      (Rt-PCR) in this case. Both IL-17A and CD70 genes were detected in this case of
      collision tumor. The results may define useful biomarkers for early diagnosis of
      mucosal melanoma and open an immunotherapeutic field for clinical management with
      the potential benefit from the immunomodulators that enhance both genes.

PMID- 20697852
TI  - Squamous odontogenic tumor.
AB  - A 24 year male presented with a radiolucent lesion associated with the right
      maxillary canine. Histologic examination of the biopsy material resulted in a
      diagnosis of squamous odontogenic tumor a rare, benign epithelial odontogenic
      neoplasm. The clinical, radiographic and morphologic features of the squamous
      odontogenic tumor are discussed.

PMID- 20697853
TI  - An unusual case of IgE-multiple myeloma presenting with systemic amyloidosis 2
      years after cervical plasmacytoma resection.
AB  - A 69-year-old man suffered from a fractured cervical vertebra, and magnetic
      resonance imaging revealed a solitary mass occupying the injured lesion. Surgical
      resection of the mass was conducted, and the infiltration of plasma cells
      expressing IgE-lambda monoclonal protein was shown on pathological investigation.
      Concurrently, a monoclonal band of IgE-lambda was shown in the sera on
      immunoelectrophoresis, and the proliferation of plasma cells (more than 10%) was
      also detected in bone marrow aspirates. A rare IgE-multiple myeloma (MM) was
      diagnosed, and careful monthly follow-up was started. During this observation
      period, the level of IgE gradually increased and, at 2 years after the initial
      diagnosis, bilateral leg edema and ascites with marked hepatosplenomegaly
      appeared. Combination chemotherapy of melphalan and prednisolone (MP) was
      started, which resulted in the partial, transient resolution of symptoms.
      Additional treatment with bortezomib and dexamethasone could neither resolve
      these clinical symptoms nor decrease the serum IgE concentration. At 5 months
      after the start of chemotherapy, amyloid deposition was suggested based on
      typical echocardiographic findings, and the diagnosis of amyloidosis was
      confirmed based on the histopathology of a liver biopsy. In spite of MP plus
      thalidomide treatment, cardiac failure due to amyloidosis aggravated, and the
      patient died of multiple organ failure. This is the second reported case in which
      IgE-MM was complicated by systemic amyloidosis.

PMID- 20697854
TI  - Blastic plasmacytoid dendritic cell neoplasm should be treated with acute
      leukemia type induction chemotherapy and allogeneic stem cell transplantation in
      first remission.
AB  - Blastic plasmacytoid dendritic cell (BPDC) neoplasm is a rare but clinically
      aggressive tumor known to be derived from the precursors of plasmacytoid
      dendritic cells (CD123+) with a high frequency of cutaneous and bone marrow
      involvement. Though majority of the patients initially respond to multi-agent
      chemotherapy, most would relapse within a year. We hereby report a patient with
      disseminated cutaneous BPDC with marrow involvement diagnosed by typical histo
      pathological and flow-cytometric findings. He was subsequently treated with
      leukemia type induction regimen followed by allogeneic stem cell transplantation
      in first complete remission. He is now 18 months posttransplantation with
      continued remission with full donor chimerism. We recognize that BPDC with marrow
      involvement behaves like acute myeloid leukemia and aggressive treatment followed
      by stem cell transplantation may lead to long-term remission in selected cases.

PMID- 20697855
TI  - Enhanced cytotoxicity of IL-24 gene-modified dendritic cells co-cultured with
      cytokine-induced killer cells to hepatocellular carcinoma cells.
AB  - As a novel human cytokine found recently, IL-24 could selectively kill tumor
      cells by multiple ways. Dendritic cells (DCs) are the major antigen-presenting
      cells. Recent studies have revealed that IL-24 can promote the antigen-presenting
      function of DCs. In this study, we evaluated the antitumor effect and mechanism
      of co-cultured cytokine-induced killer (CIK) cells and autologous DCs modified
      with IL-24 gene on hepatocellular carcinoma (HCC) cells. DCs and CIK cells were
      prepared routinely from human peripheral blood mononuclear cells. Recombinant
      adenovirus AdVGFP/IL-24 (Ad-IL24) was constructed expressing IL-24. IL-24 gene
      was transduced into DCs via Ad-IL24, the cells obtained were named DC-IL-24. We
      demonstrated that the expression rates of CD80, CD83, CD1a, HLA-DR, CD40, CXCR4
      on DC-IL-24 were significantly increased compared with those of the control
      group. DC-IL-24 produced markedly higher levels of IL-24, IL-12 and TNF-alpha as
      compared with those of DCs. On comparison with non-transfected DCs co-cultured
      with CIK cells, transfected DCs co-cultured with CIK cells had a significant
      higher lytic activity against SMMC7721 cells, a HCC cell line.

PMID- 20697856
TI  - Absence of gain-of-function JAK1 and JAK3 mutations in adult T cell
      leukemia/lymphoma.
AB  - Janus kinase 1 (JAK1) and JAK3 plays a critical role in lymphocyte proliferation
      and differentiation. Somatic JAK1 mutations are found in 18% of adult precursor T
      acute lymphoblastic leukemias and somatic JAK3 mutations are found in 3.3% of
      cutaneous T cell lymphomas. Some of the mutations are confirmed as a gain-of
      function mutation and are assumed to be involved in leukemogenesis. Adult T cell
      leukemia/lymphoma (ATLL) is a type of T cell neoplasm, and activation of JAK/STAT
      pathways is sometimes observed in them. We investigated JAK1 and JAK3 mutations
      in 20 ATLL patients. No JAK1 mutations were found, and five types of single
      nucleotide polymorphisms were observed in 12 cases, whose frequencies almost
      match those in Asian populations. As for JAK3, a synonymous mutation was found in
      one case. JAK1 and JAK3 mutations are unlikely involved in the leukemogenesis of
      ATLL.

PMID- 20697857
TI  - CT assessment of breast cancer for pathological involvement of four or more
      axillary nodes.
AB  - BACKGROUND: To predict the likelihood of >=4 pathologically positive axillary
      nodes in breast cancer patients by computed tomography (CT) before neoadjuvant
      chemotherapy (NAC). METHODS: Inclusion criteria for the 97 patients reviewed were
      lymph nodes (LNs) pathologically proved positive with standard level I-II
      axillary dissection, contrast-enhanced CT was performed before surgery,
      contralateral breast cancer was not present, and NAC was not given before
      surgery. The size, number, and level of both ipsilateral and contralateral
      axillary LNs were studied by contrast-enhanced high-resolution CT for
      pathologically positive LNs in breast cancer patients. RESULTS: Level III LN was
      only detected in ipsilateral axilla of patients with >=4 pathologically involved
      nodes. The number of ipsilateral level I-II LNs is the only factor significantly
      related to the pathological involvement of >=4 axillary nodes. Increasing numbers
      of contralateral level I-II LNs are significantly related to increasing numbers
      of ipsilateral level I-II LNs. For the criterion of maximal LN size >=5 mm, if
      contralateral level I-II LNs were negative and the cutoff points for ipsilateral
      level I-II LNs were 0-2 and >=3, the sensitivity and specificity for >=4
      pathologically involved nodes would be 84.6 and 73.3%. If contralateral I-II LNs
      were positive, the negative predictive value was 80.0%. CONCLUSION: Level III LN
      detection in ipsilateral axilla and the number of level I-II LNs in bilateral
      axilla will be helpful to predict >=4 pathologically positive axillary nodes.

PMID- 20697858
TI  - Associations between religious involvement and behavioral risk factors for
      HIV/AIDS in American women and men in a national health survey.
AB  - BACKGROUND: Acquired immunodeficiency syndrome (AIDS), caused by human
      immunodeficiency virus (HIV), is a leading cause of death. PURPOSE: We tested the
      hypothesis that religious variables would be inversely associated with prevalence
      of HIV/AIDS risk factors. METHODS: A 2002 national survey included 9,837
      individuals aged 15-44 years with complete data on religious involvement, sexual,
      and drug use behaviors. RESULTS: Women who never attended services had over two
      times greater odds of reporting HIV risk factors than those attending weekly or
      more after adjusting for age and race/ethnicity (p < 0.0001) and over 60% greater
      after adjusting for multiple confounders, but no significant association was seen
      in men. Mainline Protestants had lower odds of reporting risk factors than those
      with no affiliation. No significant independent associations were found with
      importance of religion. CONCLUSIONS: Women with public religious involvement had
      lower prevalence of any HIV risk factors while only affiliation was so associated
      in men.

PMID- 20697859
TI  - Review and meta-analysis of couple-oriented interventions for chronic illness.
AB  - BACKGROUND: Evidence continues to build for the impact of the marital
      relationship on health as well as the negative impact of illness on the partner.
      Targeting both patient and partner may enhance the efficacy of psychosocial or
      behavioral interventions for chronic illness. PURPOSE: The purpose of this report
      is to present a cross-disease review of the characteristics and findings of
      studies evaluating couple-oriented interventions for chronic physical illness.
      METHODS: We conducted a qualitative review of 33 studies and meta-analyses for a
      subset of 25 studies. RESULTS: Identified studies focused on cancer, arthritis,
      cardiovascular disease, chronic pain, HIV, and Type 2 diabetes. Couple
      interventions had significant effects on patient depressive symptoms (d = 0.18, p
      < 0.01, k = 20), marital functioning (d = 0.17, p < 0.01, k = 18), and pain (d =
      0.19, p < 0.01, k = 14) and were more efficacious than either patient
      psychosocial intervention or usual care. CONCLUSIONS: Couple-oriented
      interventions have small effects that may be strengthened by targeting partners'
      influence on patient health behaviors and focusing on couples with high illness
      related conflict, low partner support, or low overall marital quality. Directions
      for future research include assessment of outcomes for both patient and partner,
      comparison of couple interventions to evidence-based patient interventions, and
      evaluation of mechanisms of change.

PMID- 20697860
TI  - An explicit strategy prevails when the cerebellum fails to compute movement
      errors.
AB  - In sensorimotor adaptation, explicit cognitive strategies are thought to be
      unnecessary because the motor system implicitly corrects performance throughout
      training. This seemingly automatic process involves computing an error between
      the planned movement and actual feedback of the movement. When explicitly
      provided with an effective strategy to overcome an experimentally induced visual
      perturbation, people are immediately successful and regain good task performance.
      However, as training continues, their accuracy gets worse over time. This
      counterintuitive result has been attributed to the independence of implicit motor
      processes and explicit cognitive strategies. The cerebellum has been hypothesized
      to be critical for the computation of the motor error signals that are necessary
      for implicit adaptation. We explored this hypothesis by testing patients with
      cerebellar degeneration on a motor learning task that puts the explicit and
      implicit systems in conflict. Given this, we predicted that the patients would be
      better than controls in maintaining an effective strategy assuming strategic and
      adaptive processes are functionally and neurally independent. Consistent with
      this prediction, the patients were easily able to implement an explicit cognitive
      strategy and showed minimal interference from undesirable motor adaptation
      throughout training. These results further reveal the critical role of the
      cerebellum in an implicit adaptive process based on movement errors and suggest
      an asymmetrical interaction of implicit and explicit processes.

PMID- 20697861
TI  - [Outcomes of different surgical techniques for acromioclavicular joint
      stabilization in comparison].

PMID- 20697862
TI  - [Cost analysis of implant-free replacement of anterior cruciate ligament].
AB  - Replacement of the anterior cruciate ligament (ACL) is presently routinely
      carried out with autologous transplantation of the ligamentum patellae (LP),
      semintendinosus-gracilis (SGS) or quadriceps (QS) tendons. The anatomical
      positioning of the drilling canals, transplant fixation, complication rate,
      revision aspects as well as economic aspects are still under discussion. Fixation
      of the transplant can be carried out mechanically with various anchoring systems
      or using biological implant-free healing (free of cost). The compulsory and
      private health insurance companies as well as staff medical insurance
      associations guarantee a constant remuneration according to the EBM (uniform
      evaluation standard), GOA (scale of fees for physicians) or UV-GOA (accident
      insurance scale of fees for physicians). At present all health insurances accept
      the costs for implantations in outpatient areas (minus 25 Euro own contribution
      for compulsory health insurance). For inpatient treatment remuneration is
      according to the flat-rate scale (diagnosis-related groups). Costs for implants,
      which are increasing over the years, diminish the economic result in this case.
      The technique of implant-free replacement of ACLs is cheaper, with fewer
      complications and achieves functional results for fixation of the transplant
      which are comparable to techniques with implants. This also applies to the double
      bundle technique. Implant-free replacement of ACLs with the patellar tendon is a
      suitable, uncomplicated operation technique with comparably low costs and belongs
      to the state of the art according to Hertel, Petersen and other authors. This
      method already has a valuable place in surgery of the ACL.

PMID- 20697863
TI  - [Implant-free anterior cruciate ligament reconstruction with diamond instruments.
      A biological and anatomic method for every ligament transplantation].
AB  - Hamstring and patella tendons are usually used for anterior cruciate ligament
      (ACL) reconstruction and fixed with foreign material, partially executed far from
      the original point of insertion. Besides the biomechanical questions bone defects
      are a severe problem in cases of revision. We developed a biological method with
      diamond cutting instruments for graft fixation with bone dowels near the native
      insertion. The graft is tensioned and fixed in 120 degrees knee flexion and is
      self-adapting in extension. The technique has been used in a large number of
      cases during a prospective study with a follow-up of 10 years for patella tendon
      and 4 years for hamstring tendon grafts. In this investigation 124 patients with
      bone-patellar tendon-bone (BPTB) grafts showed an International Knee
      Documentation Committee (IKDC) score A/B in 87% after a mean follow-up of 9.6
      years, a Lachman test (maximum side-to-side difference) of 1.38+/-0.93 mm and a
      negative pivot shift test in 91% of the cases. Of the 147 patients with hamstring
      tendon grafts 89% had an IKDC score A/B after a mean follow-up of 4.3 years, a
      Lachman test of 1.14+/-0.76 mm and no pivot shift in 90% of the cases. The Tegner
      activity score decreased by -1.8 in both groups. CONCLUSION: This method allows a
      reliable biological press-fit fixation for every kind of graft near the original
      point of insertion, preventing bone defects, allowing early intensive
      rehabilitation and low costs.

PMID- 20697864
TI  - Why are East Asian ecosystems important for carbon cycle research?

PMID- 20697865
TI  - Ecosystem carbon stocks and their changes in China's grasslands.
AB  - The knowledge of carbon (C) stock and its dynamics is crucial for understanding
      the role of grassland ecosystems in China's terrestrial C cycle. To date, a
      comprehensive assessment on C balance in China's grasslands is still lacking. By
      reviewing published literature, this study aims to evaluate ecosystem C stocks
      (both vegetation biomass and soil organic C) and their changes in China's
      grasslands. Our results are summarized as follows: (1) biomass C density (C stock
      per area) of China's grasslands differed greatly among previous studies, ranging
      from 215.8 to 348.1 g C m(-2) with an average of 300.2 g C m(-2). Likewise, soil
      C density also varied greatly between 8.5 and 15.1 kg C m(-2). In total,
      ecosystem C stock in China's grasslands was estimated at 29.1 Pg C. (2) Both the
      magnitude and direction of ecosystem C changes in China's grasslands differed
      greatly among previous studies. According to recent reports, neither biomass nor
      soil C stock in China's grasslands showed a significant change during the past 20
      years, indicating that grassland ecosystems are C neutral. (3) Spatial patterns
      and temporal dynamics of grassland biomass were closely correlated with
      precipitation, while changes in soil C stocks exhibited close associations with
      soil moisture and soil texture. Human activities, such as livestock grazing and
      fencing could also affect ecosystem C dynamics in China's grasslands.

PMID- 20697866
TI  - Changes in soil organic carbon of terrestrial ecosystems in China: a mini-review.
AB  - The present study provides an overview of existing literature on changes in soil
      organic carbon (SOC) of various terrestrial ecosystems in China. Datasets from
      the literature suggest that SOC stocks in forest, grassland, shrubland and
      cropland increased between the early 1980s and the early 2000s, amounting to
      (71+/-19) Tg x a(-1). Conversion of marshland to cropland in the Sanjiang Plain
      of northeast China resulted in SOC loss of (6+/-2) Tg x a(-1) during the same
      period. Nevertheless, large uncertainties exist in these estimates, especially
      for the SOC changes in the forest, shrubland and grassland. To reduce
      uncertainty, we suggest that future research should focus on: (i) identifying
      land use changes throughout China with high spatiotemporal resolution, and
      measuring the SOC loss and sequestration due to land use change; (ii) estimating
      the changes in SOC of shrubland and non-forest trees (i.e., cash, shelter and
      landscape trees); (iii) quantifying the impacts of grassland management on the
      SOC pool; (iv) evaluating carbon changes in deep soil layers; (v) projecting SOC
      sequestration potential; and (vi) developing carbon budget models for better
      estimating the changes in SOC of terrestrial ecosystems in China.

PMID- 20697867
TI  - Biomass carbon stocks in China's forests between 2000 and 2050: a prediction
      based on forest biomass-age relationships.
AB  - China's forests are characterized by young forest age, low carbon density and a
      large area of planted forests, and thus have high potential to act as carbon
      sinks in the future. Using China's national forest inventory data during 1994
      1998 and 1999-2003, and direct field measurements, we investigated the
      relationships between forest biomass density and forest age for 36 major forest
      types. Statistical approaches and the predicted future forest area from the
      national forestry development plan were applied to estimate the potential of
      forest biomass carbon storage in China during 2000-2050. Under an assumption of
      continuous natural forest growth, China's existing forest biomass carbon (C)
      stock would increase from 5.86 Pg C (1 Pg=10(15) g) in 1999-2003 to 10.23 Pg C in
      2050, resulting in a total increase of 4.37 Pg C. Newly planted forests through
      afforestation and reforestation will sequestrate an additional 2.86 Pg C in
      biomass. Overall, China's forests will potentially act as a carbon sink for 7.23
      Pg C during the period 2000-2050, with an average carbon sink of 0.14 Pg C yr(
      1). This suggests that China's forests will be a significant carbon sink in the
      next 50 years.

PMID- 20697868
TI  - Changes in the distribution of South Korean forest vegetation simulated using
      thermal gradient indices.
AB  - To predict changes in South Korean vegetation distribution, the Warmth Index (WI)
      and the Minimum Temperature of the Coldest Month Index (MTCI) were used.
      Historical climate data of the past 30 years, from 1971 to 2000, was obtained
      from the Korea Meteorological Administration. The Fifth-Generation National
      Center for Atmospheric Research (NCAR) /Penn State Mesoscale Model (MM5) was used
      as a source for future climatic data under the A1B scenario from the Special
      Report on Emission Scenario (SRES) of the Intergovernmental Panel on Climate
      Change (IPCC). To simulate future vegetation distribution due to climate change,
      the optimal habitat ranges of Korean tree species were delimited by the thermal
      gradient indices, such as WI and MTCI. To categorize the Thermal Analogy Groups
      (TAGs) for the tree species, the WI and MTCI were orthogonally plotted on a two
      dimensional grid map. The TAGs were then designated by the analogue composition
      of tree species belonging to the optimal WI and MTCI ranges. As a result of the
      clustering process, 22 TAGs were generated to explain the forest vegetation
      distribution in Korea. The primary change in distribution for these TAGs will
      likely be in the shrinkage of areas for the TAGs related to Pinus densiflora and
      P. koraiensis, and in the expansion of the other TAG areas, mainly occupied by
      evergreen broad-leaved trees, such as Camellia japonica, Cyclobalanopsis glauca,
      and Schima superba. Using the TAGs to explain the effects of climate change on
      vegetation distribution on a more regional scale resulted in greater detail than
      previously used global or continental scale vegetation models.

PMID- 20697869
TI  - Biomass and carbon dynamics of a tropical mountain rain forest in China.
AB  - Biometric inventories for 25 years, from 1983 to 2005, indicated that the
      Jianfengling tropical mountain rain forest in Hainan, China, was either a source
      or a modest sink of carbon. Overall, this forest was a small carbon sink with an
      accumulation rate of (0.56+/-0.22) Mg C ha(-1)yr(-1), integrated from the long
      term measurement data of two plots (P9201 and P8302). These findings were similar
      to those for African and American rain forests ((0.62+/-0.23) Mg C ha(-1)yr(-1)).
      The carbon density varied between (201.43+/-29.38) Mg C ha(-1) and (229.16+/
      39.2) Mg C ha(-1), and averaged (214.17+/-32.42) Mg C ha(-1) for plot P9201. Plot
      P8302, however, varied between (223.95+/-45.92) Mg C ha(-1) and (254.85+/-48.86)
      Mg C ha(-1), and averaged (243.35+/-47.64) Mg C ha(-1). Quadratic relationships
      were found between the strength of carbon sequestration and heavy rainstorms and
      dry months. Precipitation and evapotranspiration are two major factors
      controlling carbon sequestration in the tropical mountain rain forest.

PMID- 20697870
TI  - The biomass and aboveground net primary productivity of Schima superba
      Castanopsis carlesii forests in east China.
AB  - The biomass and productivity of Schima superba-Castanopsis carlesii forests in
      Tiantong, Zhejiang Province, were determined using overlapping quadrants and stem
      analyses. The total community biomass was (225.3+/-30.1) t hm(-2), of which the
      aboveground parts accounted for 72.0% and the underground parts accounted for
      28.0%. About 87.2% of biomass existed in the tree layer. The resprouting biomass
      was small, of which over 95.0% occurred in the shrub layer. The productivity of
      the aboveground parts of the community was (386.8+/-98.9) g m(-2)a(-1), in which
      more than 96.0% was present at the tree level. The trunk's contribution to
      productivity was the greatest, while that of leaves was the smallest. In China,
      the community biomass of subtropical evergreen broadleaved forests differs
      significantly with the age of the forest. The community biomass of the 52-year
      old S. superba-C. carlesii forests in this study was lower than the average
      biomass of subtropical evergreen broadleaved forests in China, and was lower than
      the biomass of other subtropical evergreen broadleaved forests elsewhere in the
      world. Moreover, its productivity was lower than the model estimate, indicating
      that without disturbance, this community has great developmental potential in
      terms of community biomass and productivity.

PMID- 20697871
TI  - Carbon and nitrogen storage in an age-sequence of Pinus densiflora stands in
      Korea.
AB  - The carbon (C) and nitrogen (N) storage capabilities of Pinus densiflora in six
      different stand ages (10, 27, 30, 32, 44, and 71 years old) were investigated in
      Korea. Thirty sample trees were destructively harvested and 12 were excavated.
      Samples from the above and belowground tree components, coarse woody debris
      (CWD), forest floor, and mineral soil (0-30 cm) were collected. Tree biomass was
      highest in the 71-year-old stand (202.8 t ha(-1)) and lowest in the 10-year-old
      stand (18.4 t ha(-1)). C and N storage in the mineral soil was higher in the 71
      year-old stand than in the other stands, mainly due to higher soil C and N
      concentrations. Consequently, the total ecosystem C and N storage (tree+forest
      floor+CWD+soil) was positively correlated with stand age: increasing from a
      minimum in the 10 year old stand (18.8 t C ha(-1) and 1.3 t N ha(-1)) to a
      maximum in the 71-year-old stand (201.4 t C ha(-1) and 8.5 t N ha(-1)). The total
      ecosystem C storage showed a similar sigmoidal pattern to that of tree C storage
      as a function of the age-sequence, while N storage in the CWD, forest floor and
      mineral soil showed no significant temporal trends. Our results provide important
      insights that will increase our understanding of C and N storage in P. densiflora
      stands and our ability to predict changes according to stand age in the region.

PMID- 20697872
TI  - Carbon density and distribution of six Chinese temperate forests.
AB  - Quantifying forest carbon (C) storage and distribution is important for forest C
      cycling studies and terrestrial ecosystem modeling. Forest inventory and
      allometric approaches were used to measure C density and allocation in six
      representative temperate forests of similar stand age (42-59 years old) and
      growing under the same climate in northeastern China. The forests were an aspen
      birch forest, a hardwood forest, a Korean pine plantation, a Dahurian larch
      plantation, a mixed deciduous forest, and a Mongolian oak forest. There were no
      significant differences in the C densities of ecosystem components (except for
      detritus) although the six forests had varying vegetation compositions and site
      conditions. However, the differences were significant when the C pools were
      normalized against stand basal area. The total ecosystem C density varied from
      186.9 tC hm(-2) to 349.2 tC hm(-2) across the forests. The C densities of
      vegetation, detritus, and soil ranged from 86.3-122.7 tC hm(-2), 6.5-10.5 tC hm(
      2), and 93.7-220.1 tC hm(-2), respectively, which accounted for 39.7% +/- 7.1%
      (mean +/- SD), 3.3% +/- 1.1%, and 57.0% +/- 7.9% of the total C densities,
      respectively. The overstory C pool accounted for > 99% of the total vegetation C
      pool. The foliage biomass, small root (diameter < 5mm) biomass, root-shoot ratio,
      and small root to foliage biomass ratio varied from 2.08-4.72 tC hm(-2), 0.95
      3.24 tC hm(-2), 22.0%-28.3%, and 34.5%-122.2%, respectively. The Korean pine
      plantation had the lowest foliage production efficiency (total biomass/foliage
      biomass: 22.6 g g(-1)) among the six forests, while the Dahurian larch plantation
      had the highest small root production efficiency (total biomass/small root
      biomass: 124.7 g g(-1)). The small root C density decreased with soil depth for
      all forests except for the Mongolian oak forest, in which the small roots tended
      to be vertically distributed downwards. The C density of coarse woody debris was
      significantly less in the two plantations than in the four naturally regenerated
      forests. The variability of C allocation patterns in a specific forest is jointly
      influenced by vegetation type, management history, and local water and nutrient
      availability. The study provides important data for developing and validating C
      cycling models for temperate forests.

PMID- 20697873
TI  - Biomass carbon stocks and their changes in northern China's grasslands during
      1982-2006.
AB  - Grassland covers approximately one-third of the area of China and plays an
      important role in the global terrestrial carbon (C) cycle. However, little is
      known about biomass C stocks and dynamics in these grasslands. During 2001-2005,
      we conducted five consecutive field sampling campaigns to investigate above-and
      below-ground biomass for northern China's grasslands. Using measurements obtained
      from 341 sampling sites, together with a NDVI (normalized difference vegetation
      index) time series dataset over 1982-2006, we examined changes in biomass C stock
      during the past 25 years. Our results showed that biomass C stock in northern
      China's grasslands was estimated at 557.5 Tg C (1 Tg=10(12) g), with a mean
      density of 39.5 g C m(-2) for above-ground biomass and 244.6 g C m(-2) for below
      ground biomass. An increasing rate of 0.2 Tg C yr(-1) has been observed over the
      past 25 years, but grassland biomass has not experienced a significant change
      since the late 1980s. Seasonal rainfall (January-July) was the dominant factor
      driving temporal dynamics in biomass C stock; however, the responses of grassland
      biomass to climate variables differed among various grassland types. Biomass in
      arid grasslands (i.e., desert steppe and typical steppe) was significantly
      associated with precipitation, while biomass in humid grasslands (i.e., alpine
      meadow) was positively correlated with mean January-July temperatures. These
      results suggest that different grassland ecosystems in China may show diverse
      responses to future climate changes.

PMID- 20697874
TI  - Patterns of above- and belowground biomass allocation in China's grasslands:
      evidence from individual-level observations.
AB  - Above- and belowground biomass allocation not only influences growth of
      individual plants, but also influences vegetation structures and functions, and
      consequently impacts soil carbon input as well as terrestrial ecosystem carbon
      cycling. However, due to sampling difficulties, a considerable amount of
      uncertainty remains about the root: shoot ratio (R/S), a key parameter for models
      of terrestrial ecosystem carbon cycling. We investigated biomass allocation
      patterns across a broad spatial scale. We collected data on individual plant
      biomass and systematically sampled along a transect across the temperate
      grasslands in Inner Mongolia as well as in the alpine grasslands on the Tibetan
      Plateau. Our results indicated that the median of R/S for herbaceous species was
      0.78 in China's grasslands as a whole. R/S was significantly higher in temperate
      grasslands than in alpine grasslands (0.84 vs. 0.65). The slope of the allometric
      relationship between above- and belowground biomass was steeper for temperate
      grasslands than for alpine. Our results did not support the hypothesis that
      aboveground biomass scales isometrically with belowground biomass. The R/S in
      China's grasslands was not significantly correlated with mean annual temperature
      (MAT) or mean annual precipitation (MAP). Moreover, comparisons of our results
      with previous findings indicated a large difference between R/S data from
      individual plants and communities. This might be mainly caused by the
      underestimation of R/S at the individual level as a result of an inevitable loss
      of fine roots and the overestimation of R/S in community-level surveys due to
      grazing and difficulties in identifying dead roots. Our findings suggest that
      root biomass in grasslands tended to have been overestimated in previous reports
      of R/S.

PMID- 20697875
TI  - Changes in cropland topsoil organic carbon with different fertilizations under
      long-term agro-ecosystem experiments across mainland China.
AB  - Topsoil soil organic carbon (SOC) data were collected from long-term Chinese agro
      ecosystem experiments presented in 76 reports with measurements over 1977 and
      2006. The data set comprised 481 observations (135 rice paddies and 346 dry
      croplands) of SOC under different fertilization schemes at 70 experimental sites
      (28 rice paddies and 42 dry croplands). The data set covered 16 dominant soil
      types found in croplands across 23 provinces of mainland China. The fertilization
      schemes were grouped into six categories: N (inorganic nitrogen fertilizer only),
      NP (compound inorganic nitrogen and phosphorus fertilizers), NPK (compound
      inorganic nitrogen, phosphorus and potassium fertilizers), O (organic fertilizers
      only), OF (combined inorganic/organic fertilization) and Others (other unbalanced
      fertilizations such as P only, K only, P plus K and N plus K). Relative change in
      SOC content was analyzed, and rice paddies and dry croplands soils were compared.
      There was an overall temporal increase in topsoil SOC content, and relative
      annual change (RAC, g kg(-1) yr(-1)) ranged -0.14-0.60 (0.13 on average) for dry
      cropland soils and -0.12-0.70 (0.19 on average) for rice paddies. SOC content
      increase was higher in rice paddies than in dry croplands. SOC increased across
      experimental sites, but was higher under organic fertilization and combined
      organic/inorganic fertilizations than chemical fertilizations. SOC increase was
      higher under balanced chemical fertilizations with compound N, P and K
      fertilizers than unbalanced fertilizations such as N only, N plus P, and N plus
      K. The effects of specific rational fertilizations on SOC increase persisted for
      15 years in dry croplands and 20 years in rice paddies, although RAC values
      decreased generally as the experiment duration increased. Therefore, the
      extension of rational fertilization in China's croplands may offer a technical
      option to enhance C sequestration potential and to sustain long-term crop
      productivity.

PMID- 20697876
TI  - Quantification of soil organic carbon sequestration potential in cropland: a
      model approach.
AB  - Agroecosystems have a critical role in the terrestrial carbon cycling process.
      Soil organic carbon (SOC) in cropland is of great importance for mitigating
      atmospheric carbon dioxide increases and for global food security. With an
      understanding of soil carbon saturation, we analyzed the datasets from 95 global
      long-term agricultural experiments distributed across a vast area spanning wide
      ranges of temperate, subtropical and tropical climates. We then developed a
      statistical model for estimating SOC sequestration potential in cropland. The
      model is driven by air temperature, precipitation, soil clay content and pH, and
      explains 58% of the variation in the observed soil carbon saturation (n=76).
      Model validation using independent data observed in China yielded a correlation
      coefficient R (2) of 0.74 (n=19, P<0.001). Model sensitivity analysis suggested
      that soils with high clay content and low pH in the cold, humid regions possess a
      larger carbon sequestration potential than other soils. As a case study, we
      estimated the SOC sequestration potential by applying the model in Henan
      Province. Model estimations suggested that carbon (C) density at the saturation
      state would reach an average of 32 t C ha(-1) in the top 0-20 cm soil depth.
      Using SOC density in the 1990s as a reference, cropland soils in Henan Province
      are expected to sequester an additional 100 Tg C in the future.

PMID- 20697877
TI  - Estimation of carbon storage based on individual tree detection in Pinus
      densiflora stands using a fusion of aerial photography and LiDAR data.
AB  - The objective of this study was to estimate the carbon storage capacity of Pinus
      densiflora stands using remotely sensed data by combining digital aerial
      photography with light detection and ranging (LiDAR) data. A digital canopy model
      (DCM), generated from the LiDAR data, was combined with aerial photography for
      segmenting crowns of individual trees. To eliminate errors in over and under
      segmentation, the combined image was smoothed using a Gaussian filtering method.
      The processed image was then segmented into individual trees using a marker
      controlled watershed segmentation method. After measuring the crown area from the
      segmented individual trees, the individual tree diameter at breast height (DBH)
      was estimated using a regression function developed from the relationship
      observed between the field-measured DBH and crown area. The above ground biomass
      of individual trees could be calculated by an image-derived DBH using a
      regression function developed by the Korea Forest Research Institute. The carbon
      storage, based on individual trees, was estimated by simple multiplication using
      the carbon conversion index (0.5), as suggested in guidelines from the
      Intergovernmental Panel on Climate Change. The mean carbon storage per individual
      tree was estimated and then compared with the field-measured value. This study
      suggested that the biomass and carbon storage in a large forest area can be
      effectively estimated using aerial photographs and LiDAR data.

PMID- 20697878
TI  - Estimation of effective plant area index for South Korean forests using LiDAR
      system.
AB  - Light Detection and Ranging (LiDAR) systems can be used to estimate both vertical
      and horizontal forest structure. Woody components, the leaves of trees and the
      understory can be described with high precision, using geo-registered 3D-points.
      Based on this concept, the Effective Plant Area Indices (PAI(e)) for areas of
      Korean Pine (Pinus koraiensis), Japanese Larch (Larix leptolepis) and Oak
      (Quercus spp.) were estimated by calculating the ratio of intercepted and
      incident LIDAR laser rays for the canopies of the three forest types. Initially,
      the canopy gap fraction (G ( LiDAR )) was generated by extracting the LiDAR data
      reflected from the canopy surface, or inner canopy area, using k-means
      statistics. The LiDAR-derived PAI(e) was then estimated by using G ( LIDAR ) with
      the Beer-Lambert law. A comparison of the LiDAR-derived and field-derived PAI(e)
      revealed the coefficients of determination for Korean Pine, Japanese Larch and
      Oak to be 0.82, 0.64 and 0.59, respectively. These differences between field
      based and LIDAR-based PAI(e) for the different forest types were attributed to
      the amount of leaves and branches in the forest stands. The absence of leaves, in
      the case of both Larch and Oak, meant that the LiDAR pulses were only reflected
      from branches. The probability that the LiDAR pulses are reflected from bare
      branches is low as compared to the reflection from branches with a high leaf
      density. This is because the size of the branch is smaller than the resolution
      across and along the 1 meter LIDAR laser track. Therefore, a better predictive
      accuracy would be expected for the model if the study would be repeated in late
      spring when the shoots and leaves of the deciduous trees begin to appear.

PMID- 20697882
TI  - Behavioural and physiological consequences of male reproductive trade-offs in
      edible dormice (Glis glis).
AB  - Testosterone mediates male reproductive trade-offs in vertebrates including
      mammals. In male edible dormice (Glis glis), reproductivity linked to high levels
      of testosterone reduces their ability to express torpor, which may be expected to
      dramatically increase thermoregulatory costs. Aims of this study were therefore
      to analyse behavioural and physiological consequences of reproductive activity in
      male edible dormice under ecologically and evolutionary relevant conditions in
      the field. As we frequently encountered sleeping groups in the field, we
      hypothesized that social thermoregulation should be an important measure to
      reduce energy expenditure especially in sexually active male edible dormice. Our
      results revealed that the occurrence of sleeping groups was negatively influenced
      by male body mass but not by reproductive status or ambient temperature. In
      reproductive as in non-reproductive males, the number of individuals huddling
      together was negatively influenced by their body mass. Thus in general males with
      a high body mass were sitting in smaller groups than males with a low body mass.
      However, in reproductive males group size was further negatively affected by
      ambient temperature and positively by testes size. Thus breeders formed larger
      sleeping groups at lower ambient temperatures and males with larger testes were
      found in larger groups than males with smaller testes. Measurements of oxygen
      consumption demonstrated that grouping behaviour represents an efficient strategy
      to reduce energy expenditure in edible dormice as it reduced energy requirements
      by almost 40%. In summary, results of this field study showcase how sexually
      active male edible dormice may, through behavioural adjustment, counterbalance
      high thermoregulatory costs associated with reproductive activity.

PMID- 20697883
TI  - Persistence of propargite on okra under subtropical conditions at Ludhiana,
      Punjab, India.
AB  - Residues of propargite were estimated in okra fruits by high performance liquid
      chromatography following single application of Omite 57 EC @570 and 1,140 g
      a.i./ha. Residues of propargite were confirmed by high performance thin layer
      chromatography. The average initial deposits of propargite were observed to be
      1.36 and 3.32 mg/kg, respectively, which were below its maximum residue limit of
      2 mg/kg. The residue levels of propargite dissipated below its limit of
      quantification of 0.02 mg/kg after 7 days at single dose and after 10 days at
      double dose. The half-life values (T 1(/)2) of propargite were worked out to be
      0.79 and 0.73 days, respectively, at recommended and double the recommended
      dosages.

PMID- 20697884
TI  - Mercury in cultured oysters (Crassostrea gigas Thunberg, 1793 and C. corteziensis
      Hertlein, 1951) from four coastal lagoons of the SE Gulf of California, Mexico.
AB  - In order to determine the mercury concentrations in cultured oysters from coastal
      lagoons (SE Gulf of California), several individuals of Crassostrea gigas and C.
      corteziensis were collected and their mercury levels were measured with a cold
      vapor analyzer. The mean concentrations during the rainy and dry seasons,
      respectively, were 0.70 and 0.15 microg g(-1) in C. gigas and 0.56 and 0.18
      microg g(-1) in C. corteziensis. During the rainy season, elevated mercury
      contents are apparently related to terrigen transport from the watershed, while
      during the dry season, the moderate levels are related to upwellings.

PMID- 20697885
TI  - Losartan reduces mortality in a genetic model of heart failure.
AB  - Altered Ca(2+) homoeostasis accompanies heart failure. As a model of heart
      failure, transgenic mice (TG) with selective overexpression of calsequestrin
      (CSQ) in the heart were used. CSQ is the main Ca(2+) binding protein in the lumen
      of the junctional sarcoplasmic reticulum. Overexpression of CSQ leads to
      hypertrophy, fibrosis, heart failure, cardiac arrhythmias, and ultimately
      premature death compared to littermate controls (WT). In the present study,
      cardiac hypertrophy was noted at 2 months of age (relative heart weight 6.4 +/-
      0.2 mg/g in WT and 11.2 +/- 0.3 mg/g in TG, n = 7, p < 0.05) which progressed at
      5 months of age (relative heart weight 15.5 +/- 1.1 mg/g in TG, n = 11).
      Furthermore, an increased degree of fibrosis (from 0.29 +/- 0.04 in WT to 0.77 +/
      0.06 in TG, n = 8, p < 0.05) was quantified by sirius red staining. Cardiac
      function was greatly impaired in TG as exemplified by reduced pressure
      development and cardiac arrhythmias. It is hypothesized that losartan, an
      inhibitor of angiotensin II receptors, might be able to attenuate these
      detrimental effects. Hence, TG and WT were treated for 1 or 4 months perorally
      with losartan (5 mg/kg/day) or solvent alone (control conditions) starting at 4
      weeks of age. Under control conditions, none of the WT died within the
      observation period whereas all TG died within 9 months. Losartan treatment
      reduced the mortality of TG: Mean life span was raised from 116 to 193 days (n =
      18 end, p < 0.05). Likewise, losartan reduced relative heart weight and the
      degree of fibrosis. In addition, losartan improved hemodynamic parameters, like
      left ventricular pressure and its first derivative. However, losartan treatment
      did not modify overexpression of CSQ in the heart of TG. These results imply that
      the angiotensin II receptor (type 1) contributes to heart failure due to CSQ
      overexpression, as its blockade improved survival.

PMID- 20697886
TI  - Tubular fluid secretion in the seminiferous epithelium: ion transporters and
      aquaporins in Sertoli cells.
AB  - Sertoli cells play a key role in the establishment of an adequate luminal
      environment in the seminiferous tubules of the male reproductive tract. Secretion
      of the seminiferous tubular fluid (STF) is vital for the normal occurrence of
      spermatogenesis and for providing a means of transport to the developing
      spermatozoa. However, several studies on this subject have not completely
      clarified the origin and composition of this fluid. Electrolyte and water are
      central components of STF. Sertoli cells secrete an iso-osmotic fluid with a
      higher content of K(+) than the blood and express various membrane and water
      transporters (Na(+)/K(+)-ATPase; Ca(2+)-ATPase; V-type ATPase; Cl(-) channels;
      CFTR Cl(-) channels; K(+) channels; L-, T- and N-type Ca(2+) channels; Na(+)/H(+)
      exchangers; Na(+)-driven HCO(3) (-)/Cl(-) exchangers (NDCBEs); Na(+)/HCO(3) (-)
      cotransporters (NBCes); Na(+)-K(+)-2Cl(-) cotransporter; Na(+)/Ca(2+) exchanger;
      and aquaporins 0 and 8) involved in cellular and secretory functions. Studies
      with knockout mice for some of these transporters showed tubular fluid
      accumulation and associated infertility, revealing the relevance of these
      processes for the normal occurrence of spermatogenesis. Nevertheless, the role of
      the several membrane transporters in the establishment of STF electrolyte
      composition needs to be further elucidated. This review summarizes the available
      data on the ionic composition of STF and on the Sertoli cell membrane mechanisms
      responsible for ion and water movement. Deepening the knowledge on the mechanisms
      involved in the secretion, composition and regulation of SFT is essential and
      will be a major step in understanding the infertility associated with some
      pathological conditions.

PMID- 20697887
TI  - The effect of holding potential on charge translocation by the Na+/K +-ATPase in
      the absence of potassium.
AB  - The Na(+)/K(+)-ATPase exports 3Na(+) and imports 2K(+) at the expense of the
      hydrolysis of 1 ATP. In the absence of K(+), it carries on electroneutral, Na(+)
      dependent transient charge movement (also known as "electroneutral Na(+)/Na(+)
      exchange mode") and produces a transient current containing faster and slower
      components in response to a sudden voltage step. Components with different speeds
      represent sequential release of Na(+) ions from three binding sites. The effect
      of holding potential on slow charge movement was studied in the presence of
      different concentrations of ADP(i), Na (i) (+) and Na (o) (+) with the intention
      of improving our understanding of Na (i) (+) binding. However, the manipulation
      of [ADP](i) and [Na(+)](i) did not cause as pronounced changes as predicted in
      the magnitude of charge movement (Q (tot)), which indicated that our experimental
      conditions were not able to backwardly drive reaction across the energy barrier
      to Na (i) (+) release/rebinding steps. On the contrary, lowering [Na(+)](o)
      caused evident dependence of Q (tot) on holding potential, with characteristics
      suggesting that pumps were escaping from E2P through the uncoupled Na(+) efflux
      activity.

PMID- 20697889
TI  - Currarino syndrome.

PMID- 20697888
TI  - Protein kinase C activation has distinct effects on the localization,
      phosphorylation and detergent solubility of the claudin protein family in tight
      and leaky epithelial cells.
AB  - We have previously shown that protein kinase C (PKC) activation has distinct
      effects on the structure and barrier properties of cultured epithelial cells
      (HT29 and MDCK I). Since the claudin family of tight junction (TJ)-associated
      proteins is considered to be crucial for the function of mature TJ, we assessed
      their expression patterns and cellular destination, detergent solubility and
      phosphorylation upon PKC stimulation for 2 or 18 h with phorbol myristate acetate
      (PMA). In HT29 cells, claudins 1, 3, 4 and 5 and possibly claudin 2 were
      redistributed to apical cell-cell contacts after PKC activation and the amounts
      of claudins 1, 3 and 5, but not of claudin 2, were increased in cell lysates. By
      contrast, in MDCK I cells, PMA treatment resulted in redistribution of claudins
      1, 3, 4 and 5 from the TJ and in reorganization of the proteins into more
      insoluble complexes. Claudins 1 and 4 were phosphorylated in both MDCK I and HT29
      cells, but PKC-induced changes in claudin phosphorylation state were detected
      only in MDCK I cells. A major difference between HT29 and MDCK I cells, which
      have low and high basal transepithelial electrical resistance, respectively, was
      the absence of claudin 2 in the latter. Our findings show that PKC activation
      targets in characteristic ways the expression patterns, destination, detergent
      solubility and phosphorylation state of claudins in epithelial cells with
      different capacities to form an epithelial barrier.

PMID- 20697890
TI  - Levodopa and pramipexole effects on presynaptic dopamine PET markers and
      estimated dopamine release.
AB  - PURPOSE: Levodopa and dopamine (DA) agonist therapy are two common treatments for
      Parkinson's disease (PD). There is controversy about the effects of these
      treatments on disease progression and imaging markers. Here we used multi-tracer
      positron emission tomography imaging and a unilateral 6-hydroxydopamine (6-OHDA)
      rat model of PD to evaluate in vivo the effects of chronic levodopa and
      pramipexole treatments on measurements of vesicular monoamine transporter type 2
      (VMAT2), dopamine transporter (DAT) levels, and on levodopa-induced changes in
      synaptic DA levels [Delta(DA)]. METHODS: Twenty-three unilaterally 6-OHDA
      lesioned rats underwent an 11C-dihydrotetrabenazine (DTBZ, VMAT2 marker), an 11C
      methylphenidate (MP, DAT marker), and a double 11C-raclopride (RAC, D2-type
      receptor marker) scan. They were assigned to three treatment groups: saline
      (N=7), pramipexole (N=8), and levodopa (N=8). After 4 weeks of treatment, imaging
      was repeated. RESULTS: Results showed (1) a significant treatment effect on DTBZ,
      with pramipexole decreasing DTBZ binding compared to levodopa, (2) significant
      side and treatment-striatal side interaction effects for MP, indicating that
      levodopa tends to decrease MP binding compared to pramipexole, and (3) no
      treatment effect on Delta(DA). CONCLUSION: These data indicate that while chronic
      dopaminergic pharmacological treatment affects DTBZ and MP binding, it does not
      affect levodopa-induced changes in synaptic DA level.

PMID- 20697891
TI  - The diagnostic utility of the flare phenomenon on bone scintigraphy in staging
      prostate cancer.
AB  - PURPOSE: Bone scintigraphy (BS) lacks sensitivity for detecting very early
      skeletal metastases (SM) in prostate cancer (PC) and is often limited by poor
      specificity. Also scintigraphic flare of SM can occur following effective
      treatment and mislead an early response assessment. We hypothesised that a flare
      reaction might amplify the signal from subclinical SM, increasing the sensitivity
      of BS and that the phenomenon may be specific for metastases. METHODS: We
      conducted a prospective study to determine the frequency of the flare phenomenon
      in patients with metastatic PC starting hormone therapy and to explore its
      utility in patients with negative staging scans but considered at high risk of SM
      and in those with equivocal baseline BS abnormalities. Ninety-nine patients
      commencing first-line hormone therapy had repeat BS at 6 weeks to score a flare
      reaction. RESULTS: Of 22 patients with unequivocal SM on the baseline scan, a
      flare occurred in 9 (41%). Of 36 high-risk localised prostate cancer patients
      with normal BS pre-treatment, the scan became positive for metastases at 6 weeks
      in 4 (11%). Of 41 patients with pre-treatment scintigraphic abnormalities of
      uncertain aetiology, a flare occurred in 8 cases (20%). All eight were confirmed
      to have SM by follow-up and imaging. Of the 33 remaining patients without a
      flare, 2 developed SM at 14 months and the remainder did not develop SM in a
      median follow-up period of 36 months. CONCLUSION: The flare phenomenon following
      initial hormone therapy can be used to improve both sensitivity and specificity
      of BS in PC.

PMID- 20697893
TI  - Natural killer cells and malignant haemopathies: a model for the interaction of
      cancer with innate immunity.
AB  - Despite recent progress in the therapeutic approach of malignant haemopathies,
      their prognoses remain frequently poor. Immunotherapy offers an alternative of
      great interest in this context but defect or abnormal expression of human
      leukocyte antigens (HLA), frequently observed in cancer cells, limits its
      efficiency. Natural killer (NK) cells, which are able to kill target cells in a
      HLA-independent way, represent a novel tool in the treatment of haematological
      malignancies. Abnormal NK cytolytic function is observed in all the
      haematological malignancies studied, such as acute leukaemia, myelodysplastic
      syndromes or chronic myeloid/lymphoid leukaemia. Several mechanisms are involved
      in the alterations of NK cytotoxicity: decreased expression of activating
      receptors, increased expression of inhibitory receptors or defective expression
      of NK ligands on target cells. Further studies are needed to identify how each
      type of haematological malignancy escapes from the innate immune response.
      Attempts to increase the expression of activating receptors, to counteract
      inhibitory receptors expression, or to increase NK cell cytotoxic capacities
      could overcome tumour escape from innate immunity. These therapies are based on
      monoclonal antibodies or culture of NK cells in presence of cytokines or
      dendritic cells. Moreover, many novel drugs used in haematological malignancies
      [tyrosine kinase inhibitors, IMIDs((r)), proteasome inhibitors, demethylating
      agents, histone deacetylase inhibitors (HDACis), histamine dihydrochloride]
      display interesting immunomodulatory properties that affect NK cells. These data
      suggest that combined modalities associating cytotoxic drugs with innate immunity
      modulators may represent a major breakthrough in tumour eradication.

PMID- 20697894
TI  - Characteristics of BCR-ABL kinase domain point mutations in Chinese imatinib
      resistant chronic myeloid leukemia patients.
AB  - To explore the characteristics of BCR-ABL kinase domain point mutations in
      Chinese chronic myeloid leukemia (CML) patients, a cohort of 127 patients with
      hematologic or cytogenetic resistance to imatinib are screened by direct
      sequencing. Mutations are found in 74 patients (58%). More patients with
      hematologic resistance show mutations compared to patients with cytogenetic
      resistance (70% vs 44%, p = 0.002), and more patients with acquired resistance
      present mutations compared to patients with primary resistance (68% vs 48%, p =
      0.031). Frequencies of mutations were similar in early chronic phase (ECP), late
      chronic phase (LCP), accelerated phase, and blast phase (BP) patients (56%, 58%,
      50%, and 69%, respectively; p > 0.05). Overall, 25 mutants are found in 21 amino
      acid sites, and four of them (I418V, E450A, E453L, and E455K) are first reported
      here. All patients with these four mutants either progress to or reenter the BP.
      The most frequent mutant is M244V, followed by Y253H, F359C/V/I, G250E, E255K,
      and T315I. Only seven patients (9%) have T315I mutants, and all showed
      hematologic resistance. Three of them were in the ECP and three in the LCP. Look
      back studies show that mutants were detected 0-20 (median 7) months ahead of the
      appearance of clinical resistance in 15 tested patients with acquired resistance.
      ABL mutations are common in Chinese imatinib-resistant CML patients and are
      associated with clinical resistance. Chinese patients also seem to have unique
      profiles in the types and frequencies of some mutants, the disease phases of
      patients with T315I mutation, and the frequency of mutations in CP patients.

PMID- 20697895
TI  - Resveratrol induces apoptosis MH7A human rheumatoid arthritis synovial cells in a
      sirtuin 1-dependent manner.
AB  - Resveratrol, a phytoalexin, reduced the viability of MH7A cells, a human
      rheumatoid arthritis synovial cell line. In the apoptosis assay, resveratrol
      increased TUNEL-positive cells and stimulated H2A.X phosphorylation. Resveratrol
      disrupted mitochondrial membrane potentials in MH7A cells and stimulated
      cytochrome c release from the mitochondria to the cytosol. Resveratrol activated
      caspase-3 and caspase-9 but not caspase-8 in MH7A cells. Resveratrol upregulated
      the expression of the NAD-dependent deacetylase sirtuin 1 mRNA and downregulated
      the expression of the Bcl-X(L) mRNA, and resveratrol-induced MH7A cell death,
      mitochondrial damage, and caspase-3/-9 activation were prevented by sirtinol, an
      inhibitor of sirtuin 1. The results of the present study show that resveratrol
      induces MH7A cell apoptosis by activating caspase-9 and the effector caspase-3
      along mitochondrial disruption as a result of reduced Bcl-X(L) expression,
      allowing cytochrome c release from the mitochondria into the cytosol, in a
      sirtuin 1-dependent manner. This suggests that resveratrol could suppress
      hyperplasia of synovial cells, a critical factor of rheumatoid arthritis.

PMID- 20697896
TI  - Mechanisms of strength gain in a handgrip exercise programme in rheumatoid
      arthritis.
AB  - In a progressive resistive strengthening programme, healthy individuals gain
      strength initially through neural adaptation followed by increases in muscle
      mass. Programmes are designed to maximise these responses. The physiological
      mechanisms of strength gain in RA are unknown, but their identification will help
      to develop more effective exercise programmes. The aim of this study was to
      investigate the responses to a 12-week isometric handgrip strengthening programme
      in female subjects with RA. Fourteen right-handed female subjects with RA and 14
      age-matched female controls participated in a 12-week right handgrip
      strengthening programme. Maximum grip strength (MGS) and disease activity were
      measured serially over 12 weeks. Forearm muscle volume was measured using MRI at
      baseline and 12 weeks. Significant gains in right handgrip strength were noted in
      both groups, the gains being most marked in those with RA: mean (SD; range) MGS
      (mmHg) in RA group at baseline 105.1 (48.1; 34-108) and 174.8 (76.4; 50-340) at
      12 weeks. Mean (SD; range) MGS in control group at baseline 311.7 (49.6; 220-370)
      and 357.0 (67.1; 250-540) at 12 weeks. Significant increases in forearm muscle
      volume occurred in the controls, correlating with gains in strength. No such
      changes were noted in the RA group, indicating that improvements were solely
      related to neural adaptation. Response to strength training in RA differs from
      those of healthy individuals. Significant gains in strength in individuals with
      RA can occur due to neural adaptation without gains in muscle mass during a
      strengthening programme. This has implications for the design of rehabilitation
      programmes for such subjects.

PMID- 20697897
TI  - Hereditary pancreatitis.
AB  - Hereditary chronic pancreatitis (HCP) is a rare disease in which chronic
      pancreatitis develops in childhood. HCP has autosomal dominant inheritance with
      approximately 80% penetrance. Diagnostic criteria are not universally agreed upon
      but the EUROPAC trial defined it as two first-degree relatives or at least 3
      second-degree relatives in two or more generations, with chronic pancreatitis for
      which there is no other etiology. The gene for HCP was originally identified on
      chromosome 7 and subsequently many other genes have been reported to be
      associated with HCP. To date, no single genetic alteration has been found that is
      necessary for the development of HCP. In a recent study, 81% of patients with HCP
      were found to have a mutation of the PRSS1 gene. Patients with HCP are at risk
      for developing exocrine and endocrine insufficiency and there is a 50-fold
      increased risk of pancreatic cancer in HCP patients as compared with the general
      population.

PMID- 20697898
TI  - Constipation in children with autism and autistic spectrum disorder.
AB  - BACKGROUND: Children with autistic spectrum disorders (ASDs) have long been known
      to suffer from GIT symptoms. We planned to quantify the contribution of this
      group to our constipation clinic workload, and to discover defining group
      characteristics. METHODS: The characteristics of the bowel habit of children with
      autism +/- neuro-developmental psychiatric (NDP) diagnoses were compared with
      'normal' children by retrospective chart review. Data were entered into an Excel
      spreadsheet (Microsoft Office 2007), and compared between groups. RESULTS: One
      hundred and eighteen patients presented to the Paediatric Surgical Constipation
      clinic between April 2003 and May 2008. 90 patients were otherwise normal; 18
      patients had NDP; 6 patients had ASD alone and 4 had ASD with other
      neurodevelopmental features. The median [interquartile range] age at onset in the
      ASD + NDP and normal groups was 2.5 (1-6) and 14 (4-36) months, respectively (p =
      0.03) and the median duration of history in the ASD +/- NDP and normal groups was
      61 (47-89) and 27 (13-53) months, respectively (p = 0.007). CONCLUSIONS: Autism
      spectrum disorders are an order of magnitude more common in the constipation
      clinic than in the general population. 8.5% of patients who attended our
      Paediatric Surgical Constipation clinic had autism with or without NDP deficits.
      Children with autism +/- NDP deficits have an earlier onset of symptoms, longer
      history, and some possess signs similar to those of slow transit constipation.
      These features may be inborn. A common genetic origin of gut and behavioural
      abnormalities suggests that specific targeted investigation and treatment for the
      constipation of ASD may in time be developed.

PMID- 20697899
TI  - Acute effect of a dual ETA-ETB receptor antagonist on pulmonary arterial
      vasculature in preterm lamb fetuses with surgically induced diaphragmatic hernia.
AB  - PURPOSE: To study the effects of tezosentan, a dual ETA and ETB receptor
      antagonist on the cardiopulmonary profile in a fetal lamb model of CDH in utero.
      METHODS: A diaphragmatic hernia was surgically created at day 75 of gestation.
      During 45 min of tezosentan perfusion (1 mg/kg), hemodynamic parameters
      (pulmonary and aortic pressures, left pulmonary and aortic flows, left auricle
      pressure, heart rate) were measured at day 135 of gestation. Age-matched fetal
      lambs served as control animals. Secondarily, parietal tension of vessels rings
      of pulmonary arteries was assessed in organ baths under increasing concentration
      of tezosentan. RESULTS: In CDH group, under perfusion of tezosentan, pulmonary
      artery pressure decreased from 45.8 +/- 4.1 to 37.6 +/- 5.9 mmHg (P < 0.05).
      Pulmonary artery flow and pulmonary vascular resistance remained constant. In
      control group, pulmonary artery flow increased from 153.9 +/- 15.8 to 233.4 +/-
      26 ml/min (P < 0.05). Pulmonary artery pressure did not vary. Subsequently
      calculated pulmonary vascular resistance decreased. In organ bath, no significant
      relaxation was observed. CONCLUSION: In this fetal lamb model of CDH, tezosentan
      decreased pulmonary artery pressure but did not modify pulmonary blood flow.
      Endothelin may play a role in the regulation of pulmonary vascular tone in utero.

PMID- 20697900
TI  - The management of nephroblastoma with cavo-atrial disease at presentation:
      experience from a developing country.
AB  - PURPOSE: To describe the management of cavoatrial extension of nephroblastoma in
      a developing country. PATIENTS AND METHODS: Of 406 consecutive children with
      Wilms tumour, 40 (10%) presented with tumour extension into the inferior vena
      cava (IVC) (30), right atrium or right ventricle and form the inception cohort.
      Of this group, 17 (43%) had visceral metastases and two had bilateral synchronous
      tumours. RESULTS: Neoadjuvant chemotherapy appropriate to the pre-operative stage
      caused reduction in intravascular tumour in 18 (45%) patients, allowing 3
      children who had atrial tumour at presentation to be surgically managed without
      recourse to cardiopulmonary bypass. Neoadjuvant chemotherapy also provided a
      window of opportunity to assess and manage co-morbidity especially malnutrition.
      Of the inception cohort, 31 (78%) underwent surgical resection; 23 had simple
      cavotomy, one caval resection and seven resection under cardiopulmonary bypass.
      There was one post-operative death. 77% of resected specimen contained viable
      malignant cells despite one or more cycles of neoadjuvant chemotherapy.
      Retrograde extension into caval tributaries threatened the completeness of
      resection in all patients necessitating the addition of post-operative
      radiotherapy. Of nine patients who did not undergo resection, five died pre
      operatively. Three of these children died of chemotherapy induced neutropaenic
      sepsis. Four patients refused surgical treatment. Twenty-three patients completed
      the post-operative treatment protocol (1,203 characters).

PMID- 20697901
TI  - Viscosupplementation in the management of ankle osteoarthritis: a review.
AB  - INTRODUCTION: Osteoarthritis (OA) is a disease of synovial joints and is the most
      common cause of chronic pain. Viscosupplementation (VS) with hyaluronic acid (HA)
      is largely used for knee osteoarthritis therapy but the evidence for its
      usefulness in ankle osteoarthritis is limited. The objective of this review is to
      assess the efficacy of viscosupplementation treatment of ankle osteoarthritis in
      the current literature. METHODS: The following databases were searched: Medline
      (period 2006-2008), Database of Abstract on Reviews and Effectiveness and
      Cochrane Database of Systematic Reviews. Reference lists of relevant articles
      were controlled for additional references. The search terms Review,
      Viscosupplementation (VS), Osteoarthritis (OA), Hyaluronic acid (HA), Hyaluronan,
      Sodium hyaluronate, Ankle OA, Ankle joint were used to identify all studies
      relating to the use of VS therapy for the ankle OA. Methodological quality of
      included studies was assessed by assigning level of evidence as previously
      defined by the Centre for Evidence Based Medicine (CEBM). RESULT: Seven articles
      concerning the efficacy of a total of 275 patients undergoing VS treatment for
      ankle OA were included. One European study, one Taiwanese study, one Italian
      study, one Turkish study and three American studies with level of evidence
      ranging from I to IV evaluated the following products: Hyalgan, Synvisc, Supartz,
      Adant. CONCLUSION: Viscosupplementation is used widely in knee OA and is included
      in the professional guidelines for treatment of the disease in this joint. The
      potential for treating osteoarthritis of the ankle joint by viscosupplementation
      has been suggested in the literature, however, no dosing studies have been
      published to date, and dosing in the ankle joint remains an area for discussion.
      Viscosupplementation could potentially provide an useful alternative in treating
      such patients with painful ankle OA.

PMID- 20697903
TI  - MRI performed after intratympanic gadolinium administration in patients with
      Meniere's disease: correlation with symptoms and signs.
AB  - The objective of the study was to compare the outcomes of a series of diagnostic
      parameters in Meniere's disease (MD) patients with the extent of endolymphatic
      hydrops (EH) as shown by magnetic resonance imaging (MRI) performed after intra
      tympanic gadolinium administration using 18 patients (13 males and 5 females, age
      25-78 years, median age 54.3 years) with definite MD. A 0.6-ml solution of
      Gadobutrol (1 mmol/ml) diluted 1:7 in saline was injected through the inferior
      posterior quadrant of the tympanic membrane, using a 22-gauge spinal needle. The
      patient was kept with the head rotated 45 degrees  contralaterally for 30 min
      after the injection. Twenty-four hours later, three-dimensional fluid-attenuated
      inversion recovery MRI, using a 3-Tesla unit, was performed. Prevalence and
      extension of EH in MD patients was evaluated and correlated with age, duration
      and stage of the disease, frequency of attacks, time interval from the last
      attack, functional level scale, tinnitus, aural fullness, caloric stimulation,
      electrocochleography, and vestibular evoked myogenic potentials. All patients
      showed impaired enhancement of the inner ear of variable degree with the
      vestibular portion of the labyrinth more frequently involved than the cochlea.
      Abnormal vestibular evoked myogenic potentials, duration, and stage of the
      disease were significantly correlated to the number of inner ear sites involved.
      Modern imaging makes possible the identification of the endolymphatic hydrops in
      MD patients, improving diagnostic accuracy. The role of hydrops in the clinical
      manifestations and its correlation with most of the diagnostic parameters remain,
      however, not completely clear.

PMID- 20697904
TI  - Delayed wound infection after supracricoid partial laryngectomy following failure
      of high dose radiation.
AB  - Past radiation therapy is known as a major risk factor promoting post
      supracricoid partial laryngectomy (SCPL) complications. Risk of post-SCPL
      complications may further increase following failure of high dose radiation; in
      these patients, wound infection may become evident more than 1 month after an
      uneventful post-surgical course. By defining this complication as "Delayed Wound
      Infection" and reviewing the clinical features, we intended to elucidate the
      mechanism, risk factors, and management of this post-SCPL complication. Between
      1997 and 2009, 60 patients received SCPL. The incidence of post-SCPL wound
      infection was analyzed in reflect to radiation status, radiation dose, and
      medical histories. Of 60 patients, delayed wound infection was identified in 4
      (7%); radiation doses were 65, 68, 70, and 76.8 Gy (avg. 70 Gy). Blood data
      including white blood cell and C-reactive protein showed slight elevation before
      the delayed infection became evident. Patients with high dose radiation (>= 65
      Gy) accompanied by histories of diabetes and renal insufficiency are considered a
      high risk group. Delayed re-epithelialization of the inner surface of the
      cricohyoido gap was presumed to be the main pathogenesis. Early initiation of
      antibiotics and hyperbaric oxygen therapy are effective for rapid recovery.
      "Delayed Wound Infection" was treatable and patients undergoing surgery after
      failure of high dose radiation should be managed with extra precaution, but
      should not be excluded from the indications for SCPL.

PMID- 20697905
TI  - Electromyographic signal and force comparisons during maximal voluntary isometric
      contraction in water and on dry land.
AB  - This study was designed to compare surface electromyographic (sEMG) signal and
      force production during maximal voluntary isometric contractions (MVCs) in water
      and on dry land. The reproducibility of sEMG and isometric force measurements
      between water and dry land environments was also assessed. Nine women performed
      MVC for elbow flexion and extension, hip flexion, and extension against identical
      fixed resistance in both environments. The sEMG signal from biceps brachii,
      triceps brachii, rectus femoris, and biceps femoris was recorded with waterproof
      adhesives placed over each electrode. The sEMG and force production showed no
      significant difference between water and dry land, except for HEX (p = 0.035). In
      addition, intraclass correlation coefficient values were significant and ranged
      from moderate to high (0.66-0.96) for sEMG and force production between
      environments. These results showed that the environment did not influence the
      sEMG and force in MVC.

PMID- 20697906
TI  - Exercise as a mediator of hepcidin activity in athletes.
AB  - Iron is a trace mineral used by the body in many physiological processes that are
      essential for athletic performance. However, it is common that an athlete's iron
      stores are compromised via several well-established exercise-related mechanisms
      such as hemolysis, hematuria, sweating and gastrointestinal bleeding. Recently,
      however, a new mechanism for athletics-induced iron deficiency has been proposed,
      involving the influence of physical activity on the post-exercise hepcidin
      response. Hepcidin is a liver-produced hormone that regulates iron metabolism in
      the gut and macrophages. This hormone has become the focus of recent
      investigations into altered iron metabolism in athletes, and may be a mitigating
      factor implicated in athletics-induced iron deficiency. This review attempts to
      summarize and disseminate the collective knowledge currently held regarding
      exercise and hepcidin expression, in addition to suggesting the direction for
      future research in this area.

PMID- 20697907
TI  - Differential expression of glu-tubulin in relation to mammary gland disease.
AB  - Tubulin is one of the molecular components that regulate cytosketal structure
      relating to cell differentiation, invasion, and metastasis in cancer. Recently,
      glu-tubulin, in which the C-terminal tyrosine of alpha-tubulin is removed by
      tubulin carboxypeptidase, overexpression has been reported in malignant tumors of
      the mammary gland immunohistochemically. We identified 147 cases accessioned in
      the Department of Pathology, International University of Health and Welfare
      Hospital from 2003 to 2009. Of the 78 malignant tumor cases, staining for glu
      tubulin was observed in 56 (71.8%), and only 22 cases showed no significant
      staining. However, in benign disease, glu-tubulin staining was detected in the
      cytoplasm of fibroblasts and endothelial cells, but was completely absent from
      epithelial cells in 64 of 69 cases. When the expression of glu-tubulin was
      compared between malignant tumor, benign tumor, and other benign disease, a
      significant differentiation was found among expressions of this protein. These
      results indicate that glu-tubulin represents a strong selective expression for
      cancer cells and may be useful to identify and quantify human breast cancer.

PMID- 20697908
TI  - Prevalence and molecular identification of Cryptosporidium spp. in pigs in Henan,
      China.
AB  - The distribution and public health significance of Cryptosporidium
      species/genotypes in pigs differ among geographic areas and studies. To
      characterize the prevalence of cryptosporidiosis in pigs in Henan, China, a total
      of 1,350 fecal samples from 14 farms in ten prefectures in Henan Province were
      examined. The overall prevalence of Cryptosporidium was 8.2% (111/1,350), with
      the highest infection rate (79/383 or 20.6%) in 1-2-month-old piglets and the
      lowest infection rates in 3-6-month-old pigs. Cryptosporidium-positive samples
      from 108 animals were analyzed by polymerase chain reaction (PCR)-restriction
      fragment length polymorphism analysis of the small subunit rRNA gene, and 35 were
      further analyzed by DNA sequencing of the PCR products. Two Cryptosporidium
      species/genotype were identified, including Cryptosporidium suis (94/108) and the
      Cryptosporidium pig genotype II (14/108). C. suis infection was more common in
      younger piglets whereas the pig genotype II was relatively common in older pigs.
      These findings suggest that pigs are not a major source of zoonotic
      Cryptosporidium in the study area.

PMID- 20697909
TI  - Essential oil composition and larvicidal activity of six Mediterranean aromatic
      plants against the mosquito Aedes albopictus (Diptera: Culicidae).
AB  - Laboratory bioassays on insecticidal activity of essential oils (EOs) extracted
      from six Mediterranean plants (Achillea millefolium, Lavandula angustifolia,
      Helichrysum italicum, Foeniculum vulgare, Myrtus communis, and Rosmarinus
      officinalis) were carried out against the larvae of the Culicidae mosquito Aedes
      albopictus. The chemical composition of the six EOs was also investigated.
      Results from applications showed that all tested oils had insecticidal activity,
      with differences in mortality rates as a function of both oil and dosage. At the
      highest dosage (300 ppm), EOs from H. italicum, A. millefolium, and F. vulgare
      caused higher mortality than the other three oils, with mortality rates ranging
      from 98.3% to 100%. M. communis EO induced only 36.7% larval mortality at the
      highest dosage (300 ppm), a similar value to those recorded at the same dosage by
      using R. officinalis and L. angustifolia (51.7% and 55%, respectively).
      Identified compounds ranged from 91% to 99%. The analyzed EOs had higher content
      of monoterpenoids (80-99%) than sesquiterpenes (1-15%), and they can be
      categorized into three groups on the basis of their composition. Few EOs showed
      the hydrocarbon sesquiterpenes, and these volatile compounds were generally
      predominant in comparison with the oxygenated forms, which were detected in lower
      quantities only in H. italicum (1.80%) and in M. communis (1%).

PMID- 20697910
TI  - Corvid birds (Corvidae) act as definitive hosts for Sarcocystis ovalis in moose
      (Alces alces).
AB  - Epidemiological data and a unique phylogenetic position had suggested that
      Sarcocystis ovalis in moose and red deer might use a definitive host other than
      canids, felids, or humans. Corvid birds and rats were therefore evaluated as
      potential definitive hosts for this species in a small pilot study. Four
      laboratory rats were each inoculated with 10 or 25 sarcocysts of S. ovalis
      isolated from moose, but no Sarcocystis oocysts were detected in their intestinal
      mucosa upon euthanasia 2 to 3 weeks later. At a site where large flocks of corvid
      birds (hooded crows, ravens and European magpies) fed on remnants of moose
      carcasses during the hunting period in October, fresh bird droppings were
      collected on the ground and examined microscopically and by molecular methods. By
      microscopy, a small number of typical Sarcocystis sporocysts, measuring 12.8 *
      8.4 MUm, were found in the faecal samples. These sporocysts were identified as
      belonging to S. ovalis by a polymerase chain reaction assay using specific primer
      pairs targeting the ssu rRNA gene, followed by sequence analysis. The intestinal
      contents of a crow and two magpies shot near the dumping site were also examined.
      Sarcocystis oocysts (16.1 * 12.4 MUm) and free sporocysts (12.5 * 7.9 MUm) were
      found in the intestinal mucosa/contents of one magpie (Pica pica). These
      oocysts/sporocysts were also found to belong to S. ovalis by the same molecular
      assay. This is the first report of corvid birds acting as definitive hosts for a
      species of Sarcocystis.

PMID- 20697911
TI  - Life cycle, ultrastructure, and molecular phylogeny of Crispospora chironomi g.n.
      sp.n. (Microsporidia: Terresporidia), a parasite of Chironomus plumosus L.
      (Diptera: Chironomidae).
AB  - The life cycle, ultrastructure, and molecular phylogeny of a new microsporidium
      Crispospora chironomi g.n. sp.n., a parasite of the midge Chironomus plumosus,
      are described. The parasite infects the gut epithelium of the host larvae and
      possesses sporogonies of two types, polysporoblastic and disporoblastic,
      respectively, proceeding within the same host cell. In the sporogonial sequence
      of the first type, dozens of spherical monokaryotic spores within a thick-walled
      capsule are formed. The spores are 1.5-2.0 MUm in diameter; the exospore
      possesses two to three bundles of tubular protrusions. In the sporogonial
      sequence of the second type, diplokaryotic oval spores, 2.5 * 1.5 MUm in size,
      are formed within a compartment, partially surrounded with multilayered
      membranes. Spores of both types are similar in respect to inner structure,
      possessing a well-developed extrusion apparatus with (a) the anterior vesicular
      part of the polaroplast covering the lamellar posterior one and (b) isofilar
      polar filament with several coils in one row. Small subunit ribosomal DNA
      phylogeny showed position of the new microsporidium in a cluster uniting
      microsporidia of terrestrial origin infecting diverse hosts, nested within Clade
      IV, corresponding to Class Terresporidia sensu Vossbrinck and Debrunner
      Vossbrinck (Folia Parasitol 52:131-142, 2005).

PMID- 20697912
TI  - Parasite assemblages of Nemadactylus bergi (Pisces: Latridae): the role of larval
      stages in the short-scale predictability.
AB  - The short-scale temporal repeatability in the structure and composition of
      parasite communities of Nemadactylus bergi were analyzed by comparing population
      and infracommunity descriptors in five samples caught off Mar del Plata,
      Argentina (38o 27' S, 57o 90' W) at intervals of 20 days. This is the first study
      aiming to detect relevant local or short-term processes in an area where larval
      endohelminths dominate the parasite assemblages and are expected to provide
      predictability to the communities they belong. The parasite fauna of this host
      species was composed by 18 species, 16 of them being endoparasites, among which
      larval stages accounted for most of both the number of parasite individuals found
      and the highest percentages of average similarity among infracommunities. The
      structure of parasite communities of N. bergi was, as predicted, repeatable
      across samples at short spatial and temporal scales and, as expected, this
      predictability was mainly provided by larval stages, namely Corynosoma australe
      and Grillotia carvajalregorum. These results imply that a single sample of N.
      bergi from this locality will be enough to catch the structure and intrinsic
      variability of their component communities in further studies aiming to compare
      parasite assemblages at larger spatial scales. These studies should, however,
      take into account the heterogeneity in the size of fish among samples, which
      proved to be an important confounding factor in comparisons among samples by
      affecting their similarity.

PMID- 20697913
TI  - Molecular phylogeny of monogeneans parasitizing African freshwater Cichlidae
      inferred from LSU rDNA sequences.
AB  - The African freshwater fish of Cichlidae are parasitized by five genera of
      monogeneans belonging to Dactylogyridea. Ectoparasitic Scutogyrus, Onchobdella,
      and the highly diversified Cichlidogyrus represent three genera located on the
      gills, while the endoparasitic Enterogyrus and Urogyrus are located in the
      stomach and the urinary bladder, respectively. Representatives of four
      dactylogyridean genera (except for Urogyrus) were collected from seven cichlid
      species in West Africa. The aim of this study was to investigate the phylogenetic
      relationships between ectoparasitic and endoparasitic dactylogyridaen monogeneans
      specific to African freshwater Cichlidae and other representatives of
      Dactylogyridae, including a wide range of species from both freshwater and marine
      environments. All phylogenetic analyses point to the polyphyletic origin of the
      subfamily Ancyrocephalinae. Both Enterogyrus and Onchobdella were found to be
      monophyletic. The phylogenetic position of Scutogyrus longicornis was placed
      within the Cichlidogyrus species, which suggests the non-monophyly of
      Cichlidogyrus. Therefore, we have proposed a taxonomical revision of the species
      recently considered to be Scutogyrus. However, these four dactylogyridean genera
      specific to cichlids do not form a monophyletic group. Using LSU rDNA analyses,
      we found that Enterogyrus and Onchobdella form a clade with Protogyrodactylus,
      i.e., the parasite species does not live in cichlids, which suggests that
      endoparasitism in cichlid monogeneans is not an ancestral feature.

PMID- 20697914
TI  - Differentiation of Myxobolus spp. (Myxozoa: Myxobolidae) infecting roach (Rutilus
      rutilus) in Hungary.
AB  - During a survey on fishes from Hungarian freshwaters, the occurrence of eight
      Myxobolus species was registered in roach (Rutilus rutilus L.). Most species had
      a specific location within the fish host. Of the known species infecting roach,
      the intramuscularly developing species Myxobolus pseudodispar was found to be the
      most common. Besides Myxobolus intimus and Myxobolus diversicapsularis infecting
      the capillary network of gill lamellae, Myxobolus feisti infecting the
      cartilaginous gill rays were observed. Of the "muelleri-type" Myxobolus spp,
      Myxobolus rutili and Myxobolus sommervillae sp. n. formed elongated plasmodia in
      the gill filaments outside and inside the arteria efferens, respectively, while
      Myxobolus wootteni sp. n. developed cysts in fins. Plasmodia and spores of
      Myxobolus fundamentalis sp. n. were detected in the cartilaginous gill arch under
      the basis of gill filaments. Despite similarities of some species in spore
      morphology, 18S rDNA sequences and phylogenetic analyses showed clear differences
      among all species examined. The findings of the study demonstrate that
      morphologically similar spores could only be correctly identified by considering
      the location of plasmodia and the genetic characters of the myxozoan species.

PMID- 20697915
TI  - New spot-on formulation containing chlorpyrifos for controlling horn flies on
      cattle: laboratory model of insecticide release and field trial.
AB  - A highly viscous formulation containing chlorpyrifos (RET) was evaluated under
      laboratory, pre-field, and field conditions, and compared against ear tags with
      organophosphorus insecticides. Laboratory bioassays were performed using Musca
      domestica L. and a thin layer chromatography (TLC) plate of reversed phase silica
      gel modeling a lipophilic surface. Insects were exposed to the insecticide vapors
      of both formulations, directly and indirectly to test for lateral diffusion.
      Knockdown time 50% (KT(50)) values were determined as toxicological indicators of
      insecticide release. Minimum KT(50) values of the direct effect of both
      formulations on horn flies were reached 4 weeks after being applied. The KT(50)
      effect of migrated insecticides showed that RET formulation had a maximal
      effectiveness between the fourth and tenth last week. The KT(50) effect of the
      insecticide migrating from ear tags decreased during the last 2 weeks of the
      experiment, and the KT(50) effect of the laterally migrated insecticide was
      significantly higher for the RET formulation during this period. A pre-field
      bioassay was performed by exposing pieces of rabbit leather with both
      formulations and recording the KT(50). At the end of the experiment, the KT(50)
      effect of laterally migrated insecticide was significantly higher for the RET
      formulation. Regarding vapor emission, as a general trend the KT(50) effect of
      ear tags was greater than for the RET formulation. To evaluate the horn fly
      infestation in the field bioassays, photographs of the animal were taken. The
      results shows that RET provided significant control for 11 weeks while the ear
      tags provided protection until the 12th week.

PMID- 20697919
TI  - Construction and characterization of a full-length infectious clone from a fast
      replicating, X4-tropic HIV-1 subtype B' isolate.
AB  - In HIV-1 epidemics in China, HIV-1 subtype B' is the most predominant subtype
      circulating in intravenous drug users. In this study, we constructed an HIV-1
      full-length infectious molecular clone based on the primary virus LWJ, which was
      isolated from an HIV-infected patient in Fujian Province, China. Phylogenetic and
      bootscanning analysis of the viral sequence revealed that the isolate LWJ
      belonged to HIV-1 subtype B'. The infectious clone was designated as "pLWJ". The
      virus (LWJ-c) produced from this infectious clone by in vitro transfection of
      293T cells could infect both human peripheral blood mononuclear cells (PBMCs) and
      human the T cell line MT4. Interestingly, the cloned LWJ-c virus utilized CXCR4
      as its co-receptor and could replicate in vitro with similar efficiency and
      kinetics compared to its parental primary isolate LWJ as well as the clade B
      reference virus NL4-3. The LWJ-c virus could also cause cytopathic effects in
      both PBMCs and MT cells. Sequence analysis of the envelope glycoprotein of pLWJ
      showed that a conserved GPGR motif and an arginine at position 11 were present in
      the V3 loop, which was consistent with previous reports regarding CXCR4 co
      receptor usage and syncytium-inducing (SI) phenotype. Thus, the infectious clone
      represents a fast-replicating, high-producing, CXCR4-tropic and syncytium
      inducing isolate. Given the prevalence of HIV-1 subtype B' in China, this
      infectious clone can be a very useful tool to provide a versatile molecular model
      for research focusing on the biological properties of this subtype.

PMID- 20697920
TI  - Outbreak of influenza virus A/H1N1 in a hospital ward for immunocompromised
      patients.
AB  - In February 2008, five patients were infected with the H1N1 subtype of influenza
      A virus in one hospital ward for immunocompromised patients at a hospital in
      North Rhine-Westphalia, Germany. All of these patients had an established
      haematologic disease and tested positive either for viral RNA or antigen shortly
      after the beginning of respiratory illness. In three of the patients, influenza
      virus was repeatedly detected, and four of the patients died in coincidence with
      the virus infection. Sequencing of the amplified (HA1) haemagglutinin yielded
      identical nucleotide sequences in isolates from three of the patients, whereas
      one nucleotide difference was found in the isolate of the fourth patient,
      resulting in an amino acid substitution (G153R). To investigate the source of
      infection, the medical staff (n = 104) of the hospital unit was tested and found
      negative for influenza virus RNA and antigen in pharyngeal lavages. Testing for
      influenza virus antibodies by immunofluorescence assay revealed that 12 staff
      members were positive for influenza virus A IgA antibodies. These findings
      suggest that wild-type influenza virus infections occurred within the medical
      staff at the same time the patients were infected and that the staff might have
      contributed to the circulation of virus in the hospital ward.

PMID- 20697921
TI  - Molecular characterization of pea enation mosaic virus and bean leafroll virus
      from the Pacific Northwest, USA.
AB  - The family Luteoviridae consists of eight viruses assigned to three different
      genera, Luteovirus, Polerovirus and Enamovirus. The complete genomic sequences of
      pea enation mosaic virus (genus Enamovirus) and bean leafroll virus (genus
      Luteovirus) from the Pacific Northwest, USA, were determined. Annotation,
      sequence comparisons, and phylogenetic analysis of selected genes together with
      those of known polero- and enamoviruses were conducted.

PMID- 20697922
TI  - Understanding substrate misrecognition of hydrogen peroxide dependent cytochrome
      P450 from Bacillus subtilis.
AB  - Cytochrome P450(BSbeta), a H(2)O(2)-dependent cytochrome P450 catalyzing the
      hydroxylation of long-alkyl-chain fatty acids, lacks the general acid-base
      residue around the heme, which is indispensable for the efficient generation of
      the active species using H(2)O(2). On the basis of the crystal structure of the
      palmitic acid bound form of cytochrome P450(BSbeta), it was suggested that the
      role of the general acid-base function was provided by the carboxylate group of
      fatty acids. The participation of the carboxylate group of the substrate was
      supported by the fact that cytochrome P450(BSbeta) can catalyze oxidations of
      nonnatural substrates such as styrene and ethylbenzene in the presence of a
      series of short-alkyl-chain carboxylic acids as a dummy molecule of fatty acid.
      We refer to a series of short-alkyl-chain carboxylic acids as a "decoy molecule".
      As shown here, we have clarified the crystal structure of the decoy-molecule
      bound form and elucidated that the location of its carboxylate group is virtually
      the same as that of palmitic acid in the heme cavity, indicating that the
      carboxylate group of the decoy molecule serves as the general acid-base catalyst.
      This result further confirms that the role of the acid-base function is satisfied
      by the carboxylate group of the substrates. In addition, the structure analysis
      of the substrate-free form has clarified that no remarkable structural change is
      induced by the binding of the decoy molecule as well as fatty acid. Consequently,
      whether the carboxylate group is positioned in the active site provides the
      switching mechanism of the catalytic cycle of cytochrome P450(BSbeta).

PMID- 20697923
TI  - Small bowel diverticulitis: an often overlooked cause of acute abdomen.
AB  - We present 3 cases of small bowel diverticulitis ultimately presenting to our
      Emergency Department over a span of 2 years. Though the final diagnosis was the
      same, each patient's symptomatology was different, mimicking more common
      pathologies. Thus, it is important to consider this entity when confronted with
      signs and symptoms of acute abdomen, especially in the elderly. A missed or
      delayed diagnosis can lead to costly erroneous studies, incorrect treatments and
      delay in proper management, resulting in significant morbidity and even
      mortality. The variety of presentations can often be misleading; therefore, a
      high index of suspicion is needed on the part of the Emergency Department
      physician and Radiologist.

PMID- 20697924
TI  - Laparoscopic right hemicolectomy due to colon cancer.
AB  - AIM: The aim of this study is to present our patients with laparoscopic right
      hemicolectomy due to cancer. PATIENTS AND METHODS: Between 2005 and 2009,
      laparoscopic right hemicolectomy for cancer was performed in 9 patients. RESULTS:
      The average operative time was 168 min. The average hospital stay was 5.3 days.
      There was one conversion (11.1%) to an open procedure. There were no
      postoperative complications. All the patients remain so far with no signs of
      tumor recurrence. CONCLUSION: Laparoscopic right hemicolectomy for cancer in the
      hands of an experienced laparoscopic surgeon is a safe and efficient procedure.

PMID- 20697925
TI  - Optimizing colonic cancer surgery: high ligation and complete mesocolic excision
      during right hemicolectomy.
AB  - INTRODUCTION: When performing a colonic resection for cancerous lesions, a
      complete mesocolic excision (CME) can lead to improved oncologic results. The CME
      along with the high vessel ligation, meaning the ligation of the supplying
      vessels close to their origin, can ensure maximal lymph node harvest. The
      principles of CME and high ligation have been applied by us during colonic
      resections for cancer. We present our experience with tumors of the proximal
      colon, for which a radical right hemicolectomy has been performed. PATIENTS AND
      METHODS: Between 1989 and 2008, we performed a right hemicolectomy in 115
      patients. The mean age was 65.6 years (range 35-86). The tumor was located in the
      cecum in 37% of patients, the ascending colon in 58% of the patients and the
      hepatic flexure in 5% of the patients. All patients underwent complete mesocolic
      excision and high ligation of the supplying vessels. A total of 93% (107/115) of
      these operations were performed on an elective basis. Out of all patients, 48
      (42%) received adjuvant chemotherapy. RESULTS: No patient died during the
      immediate postoperative period. The postoperative morbidity was 13.9% (16/115).
      One patient developed a metachronous rectal carcinoma 28 months after his
      surgery, for which he underwent an abdoperineal resection. The 5-year survival
      rate lies at 72.4% (55/76). Twenty patients (26.3%) died due to metastatic
      disease before completing 5 years of follow-up. The remaining 39 patients have
      been operated after the end of 2004 and have therefore not completed 5 years from
      the day of their operation yet. CONCLUSIONS: There is no doubt that standardized
      oncologic surgery shows particular importance by reducing the rate of local
      recurrence and achieving increased survival. It is important to remember that
      colon cancer treatment today is multimodal and that the improvement in patients'
      survival in the last decades is surely linked with the improvement in
      chemotherapy and the advances in the agents used. However, optimal surgery is
      with no doubt an important element of good oncological outcome, as the experience
      with rectal cancer treatment has taught us.

PMID- 20697926
TI  - Separation and purification of xylose oligomers using centrifugal partition
      chromatography.
AB  - Xylose oligomers, which have a prebiotic effect, have been used as additives to
      human and animal food. These oligomers are also the primary intermediate in
      hemicellulose degradation during the pretreatment of biomass. Centrifugal
      partition chromatography (CPC) was used in this study to separate and purify
      xylan-derived oligomers from birchwood xylan. The xylan was partially hydrolyzed
      to achieve varying degrees of polymerization at 130 degrees C using 0.98% aqueous
      sulfuric acid for 20 min with a 2.5% solid loading. The CPC solvent system
      consisting of dimethyl sulfoxide (DMSO), tetrahydrofuran (THF), and water in a
      1:6:3 volumetric ratio was used because of its ability to dissolve xylose
      oligomers of different degrees of polymerization. The CPC was operated in the
      ascending mode with the water- and DMSO-rich bottom phase acting as the
      stationary phase, while the THF-rich top phase was the eluent. This paper
      delineates a method for the production and purification of xylose monomer and
      xylose oligomers (up to xylopentaose) using CPC. The amount and purity of
      compounds collected from the CPC fractionation based on 1 g of birchwood xylan
      were 25.26 mg of xylose at 91.86% purity, 10.71 mg of xylobiose at 85.07% purity,
      4.15 mg of xylotriose at 54.71% purity, 5.03 mg of xylotetraose at 38.33% purity
      and 3.31 mg of xylopentaose at 30.43% purity.

PMID- 20697927
TI  - Enrichment of a continuous culture of Saccharomyces cerevisiae with the yeast
      Issatchenkia orientalis in the production of ethanol at increasing temperatures.
AB  - A fermentation system was continuously fed with sugar-cane syrup and operated
      with recycling of Saccharomyces cerevisiae cells at temperatures varying from 30
      to 47  degrees C. The aim of the present work was to obtain and study the
      colonies of isolates showing elongated cells of yeasts which were sporadically
      observed at the end of this continuous process. Based on a sequence of assays
      involving methods of classical taxonomy and RAPD-PCR, two groups of isolates
      showing characteristics of non-Saccharomyces yeasts were identified in the yeast
      population where S. cerevisiae was the dominant yeast. The largest group of non
      Saccharomyces yeasts, resulting from a slow proliferation over the 2 months,
      reached a final level of 29.6% at the end of the process. RAPD-PCR profiles
      obtained for the isolates of this dominant non-Saccharomyces yeast indicated that
      they were isolates of Issatchenkia orientalis. Pichia membranifaciens was the
      only species of non-Saccharomyces yeast detected together with I. orientalis but
      at a very low frequency. The optimum temperature for ethanol formation shown by
      the isolate 195B of I. orientalis was 42  degrees C. This strain also showed a
      faster ethanol formation and biomass accumulation than the thermotolerant strain
      of S. cerevisiae used as the starter of this fermentation process. Some isolates
      of I. orientalis were also able to grow better at 40  degrees C than at 30 
      degrees C on plates containing glycerol as carbon source. Yeasts able to grow and
      produce ethanol at high temperatures can extend the fermentation process beyond
      the temperature limits tolerated by S. cerevisiae.

PMID- 20697928
TI  - Molecular cloning and characterization of the global regulator LaeA in
      Penicillium citrinum.
AB  - We have cloned and analysed a laeA gene (Pci-laeA) that may control mevastatin
      biosynthesis in Penicillium citrinum. The full-length Pci-laeA sequence is 1,340
      bp with an ORF of 1,284 bp encoding 427 amino acids. It shows 95% identity with
      LaeA from P. chrysogenum. The predicted molecular mass of Pci-LaeA is 48.72 kDa
      with an estimated theoretical isoelectric point of 6.96. Pci-LaeA has a conserved
      S-adenosylmethionine binding site and a potential MlcR (a pathway specific
      regulator in mevastatin biosynthesis) binding site.

PMID- 20697929
TI  - In vitro degradation of zearalenone by Bacillus subtilis.
AB  - Zearalenone (ZEN) is a non-steroidal estrogen produced by many Fusarium species
      in cereals and other plants, and is frequently implicated in safety of foods and
      feeds. A ZEN-degrading microorganism has been isolated and identified as a
      Bacillus subtilis subspecies. It degraded 99% ZEN (1 mg kg(-1)) in liquid medium
      after 24 h and more than 95% of ZEN (0.25 mg kg(-1)) could be degraded after 48 h
      in a solid-state fermentation. This isolate can thus be used to decontaminate raw
      materials, like grains, to reduce the mycotoxin concentration.

PMID- 20697930
TI  - Ultraviolet-B radiation improves astaxanthin accumulation in green microalga
      Haematococcus pluvialis.
AB  - Ultraviolet-B (UV-B) radiation has significantly negative effect on cell survival
      rate (P < 0.01) and positive effect on astaxanthin accumulation (P < 0.01) of
      Haematococcus pluvialis. H. pluvialis accumulated 3.2 mg/g of astaxanthin when
      being exposed to 5 W/m(2) of UV-B for 60 min prior to 72 h of high light
      treatment, which was 122% higher than that of the control. This UV-B treatment
      also significantly stimulated lipid peroxidation and the value of malondialdehyde
      and glutathione peroxidase activities were 156 and 166% higher than those of
      control, respectively (P < 0.01).

PMID- 20697931
TI  - Accumulation of copper in Trichoderma reesei transformants, constructed with the
      modified Agrobacterium tumefaciens-mediated transformation technique.
AB  - A modified Agrobacterium tumefaciens-mediated transformation method was
      established for the construction of mutants with improved copper tolerance and
      accumulation capability in Trichoderma reesei. One transformant, AT01, exhibited
      the highest copper accumulation capability. With copper at 0.7 mM, AT01 removed
      13 mg copper/g biomass (removal rate of 96%), whereas the wild-type strain
      removed only 6 mg copper/g biomass (removal rate of 50%). Optimal conditions were
      a pH of 5.0 at 28 degrees C. The pigment change of Trichoderma mycelia was a
      potential indicator of copper accumulation. Electron microscopy revealed that
      copper was mainly accumulated in cell vacuoles.

PMID- 20697932
TI  - The simultaneous determination of NAD(H) and NADP(H) utilization by glutamate
      dehydrogenase.
AB  - Glutamate dehydrogenase (GDH) from vertebrates is unusual among NAD(P)H-dependent
      dehydrogenases in that it can use either NAD(H) or NADP(H) as cofactor. In this
      study, we measure the rate of cofactor utilization by bovine GDH when both
      cofactors are present. Methods for both reaction directions were developed, and
      for the first time, to our knowledge, the GDH activity has been simultaneously
      studied in the presence of both NAD(H) and NADP(H). Our data indicate that
      NADP(H) has inhibitory effects on the rate of NAD(H) utilization by GDH, a
      characteristic of GDH not previously recognized. The response of GDH to
      allosteric activators in the presence of NAD(H) and NADP(H) suggests that ADP and
      leucine moderate much of the inhibitory effect of NADP(H) on the utilization of
      NAD(H). These results illustrate that simple assumptions of cofactor preference
      by mammalian GDH are incomplete without an appreciation of allosteric effects
      when both cofactors are simultaneously present.

PMID- 20697933
TI  - Non-cladding optical fiber is available for detecting blood or liquids.
AB  - OBJECTIVES: Serious accidents during hemodialysis such as an undetected large
      amount of blood loss are often caused by venous needle dislodgement. A special
      plastic optical fiber with a low refractive index was developed for monitoring
      leakage in oil pipelines and in other industrial fields. To apply optical fiber
      as a bleeding sensor, we studied optical effects of soaking the fiber with
      liquids and blood in light-loss experimental settings. METHODS: The non-cladding
      optical fiber that was used was the fluoropolymer, PFA fiber, JUNFLONTM, 1 mm in
      diameter and 2 m in length. Light intensity was studied with an ordinary basic
      circuit with a light emitting source (880 nm) and photodiode set at both
      terminals of the fiber under certain conditions: bending the fiber, soaking with
      various mediums, or fixing the fiber with surgical tape. The soaking mediums were
      reverse osmosis (RO) water, physiological saline, glucose, porcine plasma, and
      porcine blood. The light intensities regressed to a decaying exponential function
      with the soaked length. RESULTS: The light intensity was not decreased at bending
      from 20 to 1 cm in diameter. The more the soaked length increased in all mediums,
      the more the light intensity decreased exponentially. The means of five estimated
      exponential decay constants were 0.050+/-0.006 standard deviation in RO water,
      0.485+/-0.016 in physiological saline, 0.404+/-0.022 in 5% glucose, 0.503+/-0.038
      in blood (Hct 40%), and 0.573+/-0.067 in plasma. The light intensity decreased
      from 5 V to about 1.5 V above 5 cm in the soaked length in mediums except for RO
      water and fixing with surgical tape. CONCLUSIONS: We confirmed that light
      intensity significantly and exponentially decreased with the increased length of
      the soaked fiber. This phenomena could ideally, clinically be applied to a bleed
      sensor.

PMID- 20697934
TI  - Emergency obstetrical complications in a rural African setting (Kayes, Mali): the
      link between travel time and in-hospital maternal mortality.
AB  - The West African country of Mali implemented referral systems to increase spatial
      access to emergency obstetrical care and lower maternal mortality. We test the
      hypothesis that spatial access- proxied by travel time during the rainy and dry
      seasons- is associated with in-hospital maternal mortality. Effect modification
      by caesarean section is explored. All women treated for emergency obstetrical
      complications at the referral hospital in Kayes, Mali were considered eligible
      for study. First, we conducted descriptive analyses of all emergency obstetrical
      complications treated at the referral hospital between 2005 and 2007. We
      calculated case fatality rates by obstetric diagnosis and travel time. Key
      informant interviews provided travel times. Medical registers provided clinical
      and demographic data. Second, a matched case-control study assessed the
      independent effect of travel time on maternal mortality. Stratification was used
      to explore effect modification by caesarean section. Case fatality rates
      increased with increasing travel time to the hospital. After controlling for age,
      diagnosis, and date of arrival, a travel time of four or more hours was
      significantly associated with in-hospital maternal mortality (OR: 3.83; CI: 1.31
      11.27). Travel times between 2 and 4 h were associated with increased odds of
      maternal mortality (OR 1.88), but the relationship was not significant. The
      effect of travel time on maternal mortality appears to be modified by caesarean
      section. Poor spatial access contributes to maternal mortality even in women who
      reach a health facility. Improving spatial access will help women arrive at the
      hospital in time to be treated effectively.

PMID- 20697936
TI  - DSM-5 proposals for paraphilias: suggestions for reducing false positives related
      to use of behavioral manifestations.

PMID- 20697937
TI  - Are there different types of female orgasm?
AB  - In attempt to identify and validate different types of orgasms which females have
      during sex with a partner, data collected by Mah and Binik (2002) on the
      dimensional phenomenology of female orgasm were subjected to a typological
      analysis. A total of 503 women provided adjectival descriptions of orgasms
      experienced either with a partner (n = 276) or while alone (n = 227). Latent
      class analysis revealed four orgasm types which varied systematically in terms of
      pleasure and sensations engendered. Two types, collectively labelled "good-sex
      orgasms," received higher pleasure and sensation ratings than solitary
      masturbatory ones, whereas two other types, collectively labelled "not-as-good
      sex orgasms," received lower ratings. These two higher-order groupings differed
      on a number of psychological, physical and relationship factors examined for
      purposes of validating the typology. Evolutionary thinking regarding the function
      of female orgasm informed discussion of the findings. Future research directions
      were outlined, especially the need to examine whether the same individual
      experiences different types of orgasms with partners with different
      characteristics, as evolutionary theorizing predicts should be the case.

PMID- 20697938
TI  - Clinical study on the treatment of knee osteoarthritis of Shen-Sui insufficiency
      syndrome type by electroacupuncture.
AB  - OBJECTIVE: To study the clinical effificacy of electroacupuncture (EA) on
      treating knee osteoarthritis (KOA) of Shen ()-Sui () insuffificiency (SSI)
      syndrome type. METHODS: A total of 245 patients (279 knees) of KOA-SSI were
      randomly assigned to two groups by lottery: 141 knees in the treatment group and
      138 knees in the control group. The treatment group was managed with EA at the
      dominant points of Neixiyan (Ex-LE4) and Waixiyan (Ex-LE5) as well as the
      conjugate points of Xuanzhong (GB39) and Taixi (KI3) for 30 min, once a day, with
      15 days as one course; 2 courses were applied with a 5-day interval in between.
      The control group was treated with intra-articular injection of 2 mL hyaluronic
      acid into the affected joint every 7 days for 5 times in total. The clinical
      effects on the patients in different stages were observed, and their symptom
      scores of knee and contents of cytokines, including interleukin-1 (IL-1),
      interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), prostaglandin
      E(2alpha) (PGE(2alpha)) and matrix metalloproteinases-3 (MMP-3), in the knee
      joint fluid were measured before and after treatment. RESULTS: The study was
      completed in 235 patients (263 knees); four patients (7 knees) in the treatment
      group and six patients (9 knees) in the control group dropped out. Comparison of
      therapeutic effects (excellent and effective rates) between the two groups showed
      insignificant differences (P>0.05). Symptom scores of knee and contents of
      cytokines in the knee flfluid after treatment were lowered signifificantly in the
      patients of stage I-III in both groups (P<0.05 or P<0.01). However, the lowering
      of the total symptom score of knee in the patients of stage III in the treatment
      group was more signifificant (P<0.05). CONCLUSIONS: EA could effectively
      alleviate the clinical symptoms in KOA patients of stage III, showing an effect
      superior to that of hyaluronic acid. EA also shows action in suppressing the
      secretion of IL-1, IL-6, TNF-alpha, PGE(2alpha) and MMP-3 in the knee flfluid.

PMID- 20697939
TI  - Clinical study on the treatment of gastroesophageal reflux by acupuncture.
AB  - OBJECTIVE: To explore the clinical efficacy and safety of acupuncture in treating
      gastroesophageal reflux (GER). METHODS: Sixty patients with confirmed diagnosis
      of GER were randomly assigned to two groups. The 30 patients in the treatment
      group were treated with acupuncture at acupoints Zhongwan (CV 12), bilateral
      Zusanli (ST36), Sanyinjiao (SP6), and Neiguan (PC6), once a day, for 1 week as a
      therapeutic course, with interval of 2-3 days between courses; the 30 patients in
      the control group were administered orally with omeprazole 20 mg twice a day and
      20 mg mosapride thrice a day. The treatment in both group lasted 6 weeks.
      Patients' symptoms and times of reflux attacking were recorded, the 24-h
      intraesophageal acid/bile reflux were monitored, and the endoscopic feature of
      esophageal mucous membrane was graded and scored at three time points, i.e., pre
      treatment (T0), immediately after ending the treatment course (T1) and 4 weeks
      after it (T2). Besides, the adverse reactions were also observed. RESULTS:
      Compared with those detected at T0, 24-h intraesophageal pH and bile reflux,
      endoscopic grading score and symptom score were all decreased significantly at T1
      in both groups similarly (P<0.01), showing insignificant difference between
      groups (P>0.05). These indices were reversed at T2 to high level in the control
      group (P<0.05), but the reversion did not occur in the treatment group (P>0.05).
      No serious adverse reaction was found during the therapeutic period. CONCLUSION:
      Acupuncture can effectively inhibit the intraesophageal acid and bile reflux in
      GER patients to alleviate patients' symptoms with good safety and is well
      accepted by patients.

PMID- 20697940
TI  - Effect of Tianhuang Granule on intracranial pressure and serum matrix
      metalloproteinase-9 in patients with acute cerebral hemorrhage.
AB  - OBJECTIVE: To study the effect and mechanism of Tianhuang Granule (, THG) on:
      hydrocephalus in the patients with acute cerebral hemorrhage (ACH) through
      intracranial pressure (ICP) monitoring, serum matrix metalloproteinase-9 (MMP-9)
      level observation, and National Institutes of Health Stroke Scale (NIHSS) scoring
      (for nerve function de ficit). METHODS: Sixty patients with ACH were equally
      randomized: into two groups by lottery, the control group and the THG group; all
      were treated with conventional therapy, but to the patients in the THG group, THG
      was given orally in addition for 28 days. Changes of ICP, MMP-9 expression, and
      NIHSS scores, as well as the degree of cerebral hematoma and hydrocephalus (by
      cranial CT scanning) in the patients, were estimated and compared. RESULTS: (1)
      ICP was lowered more significantly in the: THG group, showing a significant
      difference between groups on day 7 (P<0.05). (2) MMP-9 expression was down
      regulated in the THG group more significantly and earlier than that in the
      control group. (3) The degrees of cerebral hematoma and hydrocephalus in the THG
      group on day 7 were reduced significantly as compared with those on day 3
      (P<0.05), but in the control group, the day of significant reduction was delayed
      to day 14, and the degrees on day 7 and day 14 in the two groups were
      significantly different (P<0.05 and P<0.01). (4) NIHSS score was significantly
      lower in the THG group than that in the control group on day 14 and day 28
      (P<0.05 and P<0.01). CONCLUSION: THG can effectively lower ICP, down-regulate MMP
      9 expression, promote the absorption: of cerebral hematoma and hydrocephalus, and
      improve the nerve function, showing a clinical effectiveness than conventional
      therapy.

PMID- 20697941
TI  - Alleviation of cancerous pain by external compress with Xiaozheng Zhitong Paste.
AB  - OBJECTIVE: To observe the clinical effectiveness of a topical application of
      Xiaozheng Zhitong: Paste (, XZP) in alleviating the cancerous pain of patients
      with middle/late stage cancer METHODS: By: adopting a random number table, 124
      patients enrolled were randomized into the treatment group (64 patients) and the
      control group (60 patients). In addition to the basic therapy [including the
      three-ladder (3L) analgesia] used in both groups, topical application of XZP was
      given to patients in the treatment group for pain alleviation. The analgesic
      efficacy was recorded in terms of pain intensity, analgesia initiating time and
      sustaining time, and the optimal analgesic effect revealing time. Meanwhile, the
      quality of life (QOL) and adverse reactions that occurred in patients were
      recorded as well. RESULTS: The total effective rate in the treatment group was:
      84.38% (54/64), and in the control group it was 88.33% (53/60), showing no
      significant difference between them (P>0.05), but the analgesia initiating time
      and the optimal analgesia effect revealing time in the treatment group were
      significantly shorter (both P<0.01). Moreover, XZP was better in improving
      patients' QOL, showing more significant improvements in the treatment group than
      those in the control group in aspects of mental condition, walking capacity,
      working capacity, social acceptability, sleep and joy of living (P<0.05 or
      P<0.01). Lower incidence of adverse reactions, such as nausea, vomiting, mouth
      dryness, dizziness, etc., especially constipation, was noted in the treatment
      group (P<0.05 or P<0.01). CONCLUSION: Applying an external compress: of XZP
      showed a synergistic action with 3L analgesia for shortening the initiating time
      and the optimal effect revealing time, and could evidently enhance patients' QOL
      with fewer adverse reactions.

PMID- 20697942
TI  - Effects of repeated electroacupuncture on beta-endorphin and adrencorticotropic
      hormone levels in the hypothalamus and pituitary in rats with chronic pain and
      ovariectomy.
AB  - OBJECTIVE: To explore the mechanism of electroacupuncture (EA)-induced cumulative
      analgesic effects on chronic pain in rats with or without ovariectomy (OVX).
      METHODS: A total of 110 female Wistar rats were randomized into normal control
      (n=10), chronic constrictive injury (CCI, n=10), CCI+EA (n=30), OVX+CCI (n=30),
      and OVX+CCI+EA (n=30) groups. Each of the latter 3 groups was further divided
      into 2 days (2 d), 2 weeks (2 W) and 3 weeks (3 W) subgroups, respectively (n=10
      in each subgroup). The CCI pain model was established by ligature of the right
      sciatic nerve, and the memory impairment model duplicated by OVX. The paw
      withdrawal latency (PWL, pain threshold) of the bilateral footplates was detected
      by radiant heat irradiation, and the bilateral difference in PWL (PWLD) was used
      to evaluate changes in the pain reaction. Morris water maze test was conducted
      for evaluating the rats' learning-memory ability. EA was applied to bilateral
      Zusanli (ST36) and Yanglingquan (GB34) for 2 d, 2 W and 3 W, respectively.
      Pituitary and hypothalamic beta-endorphin (EP) and adrenocorticotrophic hormone
      (ACTH) contents were detected by immunoradioassay. RESULTS: Compared with the CCI
      group, PWLD of the CCI+EA-3 W group decreased significantly (P<0.05). Compared
      with the OVX+CCI group, PWLD of the OVX+CCI+EA-3 W group was lowered considerably
      (P<0.05), but the value was markedly higher than its basal value and those of the
      normal control and CCI+EA groups (P<0.05). In comparison with the sham-OVX group,
      the escape latency, swimming distance (SD) in the target quadrant and total SD
      were increased remarkably in the OVX group (P<0.05), while the number of target
      platform crossings was decreased significantly (P<0.05), suggesting an impairment
      of the OVX rats' learning-memory ability. In simple CCI rats, both beta-EP and
      ACTH contents of the pituitary increased markedly (P<0.05), and those of the
      hypothalamus decreased obviously compared to the normal control group (P<0.05).
      After EA, pituitary and hypothalamic ACTH levels were significantly lowered at 2
      d and hypothalamic ACTH and beta-EP contents increased obviously at 3 W in
      comparison with the CCI group (P<0.05). In OVX+CCI rats, following EA, pituitary
      beta-EP contents at 2 d, 2 W and 3 W, and hypothalamic beta-EP and ACTH contents
      at 2 W and hypothalamic ACTH levels at 3 W increased significantly (P<0.05), but
      hypothalamic beta-EP level at 3W decreased markedly (P<0.05). The effects of
      repeated EA in lowering pituitary ACTH and raising hypothalamic beta-EP and ACTH
      levels disappeared after OVX+CCI. CONCLUSIONS: Repeated EA has a cumulative
      analgesic effect, which is closely associated with its effects in regulating
      pituitary and hypothalamic beta-EP and ACTH levels. OVX may weaken the analgesic
      effect of EA by affecting hypothalamic-pituitary axis activity.

PMID- 20697943
TI  - Effects of Bushen Tongmai Recipe on protein kinase Balpha expression in
      polycystic ovary rats with insulin resistance.
AB  - OBJECTIVE: To observe the effects of Bushen Tongmai Recipe (, BSTMR) on mRNA and
      protein expressions of protein kinase B alpha (PKB alpha) in hepatic, adipose,
      muscular, and ovarian tissues of polycystic ovary (PCO) rats with insulin
      resistance (IR) and to explore the possible molecular mechanism of BSTMR in
      treating IR and ovulation dysfunction. METHODS: Female 22-day-old SD rats were
      injected subcutaneously with sodium prasterone sulfate (9 mg.100g(-1).d(-1)) for
      20 days and fed with high-fat diet for 80 days to induce PCO rats with IR. Then,
      the PCO rats were randomly divided into the model group (n=23) and the treated
      group (n=21). The treated group was administered with BSTMR for 2 weeks.
      Meanwhile, a group with 15 rats of the same age was used as the control group.
      The histological changes in the ovaries were examined. Fasting blood glucose
      (FBG) was determined by the glucose oxidase method. Serum fasting insulin (Fins)
      was determined by radioimmunoassay (RIA). The mRNA level of PKBalpha was measured
      by reverse transcription polymerase chain reaction (RT-PCR). Immunohistochemistry
      staining and Western blot analysis were employed to detect the protein expression
      in target tissues. RESULTS: Compared with the control group, the ovaries in the
      model group showed multiple follicular cysts, levels of FBG and Fins in the model
      group increased markedly (P<0.05 or P<0.01, respectively), and the insulin
      sensitive index (ISI) decreased obviously (P<0.01). The mRNA and protein
      expressions of PKBalpha in target tissues in the model group were dramatically
      lower than those in the control group (P<0.05 or P<0.01). Compared with the model
      group, the stratum granulosum of the ovarian follicle in the treated group
      increased markedly, the level of Fins in the treated group decreased obviously
      (P<0.01), ISI in the treated group improved markedly (P<0.01), and the mRNA and
      protein expressions of PKBalpha in target tissues of the treated rats were
      elevated significantly (P<0.05 or P<0.01). CONCLUSION: BSTMR could improve IR and
      ovulation dysfunction in PCO rats with IR, and its molecular mechanisms might be
      closely related with the elevation of mRNA and protein expressions of PKBalpha in
      target tissues of PCO rats with IR.

PMID- 20697944
TI  - Shenmai injection inhibiting the extracellular signal regulated kinase-induced
      human airway smooth muscle proliferation in asthma.
AB  - OBJECTIVE: To investigate the relationship between the proliferation of
      sensitized human airway smooth muscle cells (HASMCs) and the expression of
      extracellular signal regulated kinase (ERK) and the effect of Shenmai Injection
      (SMI) on HASMCs. METHODS: The HASMCs cultured in vitro were divided into three
      groups: (1) control group; (2) sensitized group: containing 10% asthmatic serum;
      (3) SMI group: further divided into three different concentration subgroups
      interferred with 10 microL/mL, 50 microL/mL, and 100 microL/mL SMI, respectively.
      The proliferation of HASMCs was detected using MTT method, the expression of
      proliferating cell nucleus antigen (PCNA) in HASMCs was detected using
      immunocytochemical staining, and the expression of phosphoration-ERK1/2 (p
      ERK1/2) protein was detected using Western-blot. RESULTS: After passive
      sensitization,: the optical density value (A A(490) value) of HASMCs was
      significantly increased from 0.366+/-0.086 to 0.839+/- 0.168 (P<0.05). In
      addition, the expression of PCNA was significantly increased from 28.7%+/-5.9% in
      the control group to 69.8%+/-7.5% in the sensitized group (P<0.05). At the same
      time, the expression of p-ERK1/2 in passively sensitized HASMCs was significantly
      increased compared with the control group (all P<0.05). After application of 10
      microL/mL, 50 microL/mL, and 100 microL/mL SMI to the cultured media of passively
      sensitized group, the A(570) value was significantly decreased from 0.839+/-0.168
      to 0.612+/-0.100, 0.412+/-0.092, and 0.339+/-0.077, respectively (P<0.05).
      Moreover, the expression of PCNA was significantly decreased from 69.8%+/-7.5% to
      57.8%+/-6.2%, 40.7%+/-5.4%, and 26.1%+/-5.2%, respectively. At the same time, the
      expression of p-ERK1/2 in each SMI group was significantly decreased compared
      with the sensitized group (all P<0.05). CONCLUSION: ERK signal transduction
      pathway may be involved in the airway remodeling in asthma. The expression of ERK
      can be inhibited by SMI in a dose-dependent manner, thus preventing the
      proliferation of HASMCs.

PMID- 20697945
TI  - Antimicrobial activity of the methanolic extract and compounds from the stem bark
      of Drypetes tessmanniana.
AB  - OBJECTIVE: To evaluate the antimicrobial activity of the methanol extract from
      the stem bark of Drypetes tessmanniana, fractions (DTB1-5) as well as compounds
      [friedelin (2), 3,7-dioxofriedelane (3), 3,15-dioxofriedelane (4), 3beta- O-(E)
      3,5-dihydroxycinnamoyl-11-oxo-olean-12-ene (6), and 3beta,6alpha-dihydroxylup
      20(29)-ene (7). METHODS: Agar disc diffusion was used to determine the
      sensitivity of the above samples, whilst the microdilution method was used for
      the determination of the minimal inhibitory concentration (MIC) and the minimal
      microbicidal concentrations (MMC). RESULTS: The diffusion test showed that the
      crude extract was able to prevent the growth of all tested organisms. All other
      samples showed selective activity. The inhibitory effect of the fraction DTB2 was
      noted on 63.7%, that of DTB1 and DBT3 on 54.6%, whilst DTB4 and DTB5 were active
      on 9.1% of the 11 tested organisms. The tested compounds prevented the growth of
      81.8% of the tested microbial species for compounds 3 and 4, 36.7% for compound
      6, and 18.2% for compound 7. The results of the MIC determinations indicated
      perceptible values for DTB and compound 4 on 81.8% of the tested organisms. For
      other samples, MICs were detected on 0-63.7%. The lowest MIC value (78.12
      microg/mL) for the crude extract and fractions (DTB2) was observed on M.
      audouinii. The corresponding value for isolated compounds (156.25 microg/mL) was
      noted with compounds 3 on S. faecalis and 4 on M. audouinii audouinii. The
      results of the MMC determination suggested that the microbicidal effect of most
      of the tested samples on the studied microorganisms could be expected.
      CONCLUSION: The methanol extract from the stem bark of Drypetes. tessmanniana
      (Euphorbiaceae) as well as some of the isolated compounds might be potential
      sources of new antimicrobial drugs.

PMID- 20697946
TI  - Effects of Yinian Jiangya Decoction containing serum on cytokines secretion of
      vascular endothelium of spontaneously hypertensive rats.
AB  - OBJECTIVE: To observe the effects of Yinian Jiangya Decoction (YNJYD) on cytokine
      secretion in spontaneoulsy hypertensive rats (SHRs) vascular endothelium.
      METHODS: Aortic endothelial cells (ECs) were primarily cultured from SHRs; male
      SD rats were treated with different doses (high, medium, and low doses) of YNJYD,
      the blood was collected on the 21st day, and then, the serum was separated. ECs
      were cocultured with the serum for different time courses, and the culture
      supernatant concentrations of endothelin (ET)-1, nitric oxide (NO), tissue-type
      plasminogen activator (t-PA), and plasminogen activator inhibitor (PAI-1) were
      determined by ABC-ELISA methods. RESULTS: ET-1, NO, t-PA, and PAI-1 levels in
      endothelial cell culture supernatant were increased in a time-dependent manner;
      YNJYD could significantly elevate NO and t-PA expressions in ECs, while ET-1 and
      PAI-1 expressions were dramatically decreased; these effects of YNJYD were in a
      concentration-dependent manner. CONCLUSION: The therapeutic effect of YNJYD on
      hypertension is attributed to its effect on regulating vessel dilation and blood
      coagulation, in which ET-1/NO and PAI-1/t-PA are two pairs of pivotal mediators.

PMID- 20697947
TI  - Clinical observation on the treatment of chronic severe hepatitis B by retention
      enema with Huchang Jiedu Decoction.
AB  - OBJECTIVE: To observe the efficacy of retention enema with Huchang Jiedu
      Decoction (, HJD) in treating chronic severe hepatitis B (CSHB). METHODS: Sixty
      patients of CSHB were equally randomized into the treated group and the control
      group. Both groups were treated with conventional integrative medicine, but to
      patients in the treated group, retention enema with HJD was given in addition,
      once every day for 3 weeks. The dominant symptoms, physical signs, and related
      biochemical indices, as well as the incidence of complications in patients before
      and after treatment, were observed. RESULTS: Good therapeutic effects were shown
      in the treated group, with a total effective rate better than that in the control
      group (83.3% versus 60.0%, P<0.05), superior in terms of lowering alanine
      aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil),
      globulin (Glb), and endotoxin (ET) levels and increasing prothrombin activity
      (PTA), total cholesterol (TC), and calcium (Ca) levels, as well as eliminating
      ascites and preventing hepatic encephalopathy (P<0.05); especially in treating
      middle/early stage patients with Chinese medicine syndrome differentiated as
      water-toxin accumulation pattern. CONCLUSION: Retention enema with HJD is surely
      effective in treating CSHB, and its primary mechanism may be related to the
      mitigation of enterogenous endotoxemia.

PMID- 20697948
TI  - Clinical observation on the treatment of chronic urticaria with total glucosides
      of paeony capsule combined with citirizine.
AB  - OBJECTIVE: To assess the effect and adverse reaction of total glucosides of
      paeony capsule (TGPC) in combining with citirizine for the treatment of chronic
      urticaria. METHODS: A total of 120 patients were assigned to two groups by
      lottery, 65 in the treated group and 55 in the control group. They all were
      orally treated with citirizine tablet 10 mg per day, but to the treated group,
      additional 0.2 g TGPC was given three times per day, the therapeutic course for
      both groups was 4 weeks. The effectiveness of treatment was observed, and the
      changes of total symptom score, serum levels of interleukin-4 (IL-4), and
      immunoglobulin E (IgE) were measured before and after treatment. Moreover, a
      follow-up was carried out one month after ending the treatment. RESULTS: The
      dropped cases were two in the treated group and seven in the control group; so,
      the study was accomplished on 63 patients in the treated group and 48 patients in
      the control group. The total effective rate was assessed at 73.02% (46/63) in the
      treated group, which was significantly higher than 47.92% (23/48) in the control
      group (P<0.01). After treatment, the total symptom score decreased in both
      groups, but the decrement in the treated group was more significant (P<0.05).
      Serum levels of IL-4 and IgE in the treated group lowered significantly, while
      the changes in the control group were insignificant, so statistical significant
      differences were shown between groups (P<0.01). A follow-up study showed that the
      relapse rate in the treated group was 30.00% (6/20), while that in the control
      group was 90.00% (9/10), and the former was lower than the latter (P<0.01).
      Adverse reactions, revealed as drowsiness, dizziness, and weakness, were seen in
      eight cases and seven cases in the two groups, respectively. Besides, mild
      diarrhea occurred in two cases of the treated group. CONCLUSIONS: The treatment
      of TGPC combining citirizine shows definite curative effect in treating chronic
      urticaria, with low relapse rate and without evident adverse reaction. Its
      therapeutic effect might be realized by means of regulating patients' immune
      function. Besides, the medication should be continued for a rather long period to
      achieve the full effect.

PMID- 20697949
TI  - Reflections on the research status of Kampo medicine: a most rewarding visit to
      Japan.

PMID- 20697950
TI  - Anticancer effects of HESA-A: an herbal marine compound.

PMID- 20697952
TI  - Progress on integrated Chinese and Western medicine in the treatment of
      osteoarthritis.
AB  - Osteoarthritis (OA) is a chronic degenerative disease of the joints caused by
      wide variety of factors. factors. This paper provides a review of the clinical
      and experimental research on integrated Chinese and Western medicine in the
      treatment of osteoarthritis. Western medicine in the treatment of osteoarthritis.
      (1) Clinical research: integrated Chinese and Western medicine therapies were
      used including physiotherapy, medications, acupuncture, functional training,
      intra-articular injection of sodium hyaluronate therapy, and arthroscopic
      debridement with Chinese medicine articular iontophoresis therapy. articular
      iontophoresis therapy. (2) Experimental research: modern methods were used in
      studying the mechanism of Chinese medicine in slowing down cartilage
      degeneration, promoting articular cartilage repair, inhibiting synovial
      inflammation, and blocking cartilage destruction. inflammation, and blocking
      cartilage destruction. In addition, this article also reviews the advantages,
      prospects, and problems of the therapies. and problems of the therapies.

PMID- 20697951
TI  - Application and assessment of Chinese arsenic drugs in treating malignant
      hematopathy in China.
AB  - Chinese arsenic drugs have been applied in Chinese medicine for several
      centuries. Beginning from 1970s, arsenic containing drugs have been generally
      used for the treatment of malignant hematologic diseases including acute
      promyelocytic leukemia, myelodysplastic syndrome, and multiple myeloma. No matter
      what ingredients of arsenic drugs were applied, either arsenic trioxide, arsenic
      disulfide, or arsenic containing Chinese herbal compositions including Qinghuang
      Powder and Realgar-Indigo naturalis formula, they all provided the distinct
      approaches for the management of malignant hematologic diseases, and good
      clinical efficacy was obtained with mild adverse reactions. Moreover, the
      mechanisms of action have been continually elucidated.

PMID- 20697953
TI  - An association analysis of reelin gene (RELN) polymorphisms with childhood
      epilepsy in eastern Indian population from West Bengal.
AB  - Epilepsy is a common neurological condition characterized by unprovoked seizure
      attacks. Early brain developmental abnormalities involving neuronal migration and
      lamination are implicated in childhood epilepsy. Reelin, a neuronal-signaling
      molecule plays a crucial role in these migratory processes. Therefore, reelin
      gene (RELN), which is located on human chromosome 7q22 is considered as a
      potential candidate gene for childhood epilepsy. In this study, we recruited 63
      patients with childhood-onset epilepsy and 103 healthy controls from West Bengal
      in India. Genomic DNA isolated from leukocytes of cases and control individuals
      were used for genotyping analysis of 16 markers of RELN. Case-control analysis
      revealed significant over-representation of G/C and (G/C+C/C) genotypes, and C
      allele of exon 22 G/C marker (rs362691) in cases as compared to controls. Pair
      wise linkage disequilibrium analysis demonstrated two separate LD blocks with
      moderately high D' values in epileptic cases. Based on these data, we have
      carried out haplotype case-control analysis. Even though we found over
      representation of A-C haplotype of intron 12 A/C/exon 22 G/C markers and
      haplotype combination involving G-allele of exon 22 marker in cases and controls,
      respectively, the overall test was not significant. LD in this region involving
      this marker was also more robust in epileptic cases. Taken together, the results
      provide possible evidences for association of exon 22 G/C marker or any marker in
      the vicinity, which is in LD with this marker with epilepsy in the West Bengal
      population. Further investigations involving higher sample sizes are warranted to
      validate the present finding.

PMID- 20697954
TI  - Dyslexia-associated kiaa0319-like protein interacts with axon guidance receptor
      nogo receptor 1.
AB  - To identify the putative interacting partners for Kiaa0319-like protein. KIAA0319
      like, located near the dyslexia susceptibility locus, DYX8 in chromosome 1p34.3,
      has been suggested as a positional candidate for developmental dyslexia due to
      its homology with another gene, KIAA0319 which has been strongly established as a
      candidate gene for developmental dyslexia. Previous research has shown that a
      single marker, rs7523017 (P = 0.042) has been associated with developmental
      dyslexia by a Canadian group. There is little functional information about this
      gene and protein. In this article, we put forward further evidence that support
      Kiaa0319-like is a candidate for this disorder. A yeast-2-hybrid screen and co
      immunopreciptiation assays were performed to find protein interacting partners of
      KIAA0319L. A human cortex immunohistochemistry assay was performed to show the
      colocalization of Kiaa0319-like and its specific interacting partner in cells.
      Nogo Receptor 1 (NgR1), an axon guidance receptor, was identified to have
      physical interactions with Kiaa0319-like protein. These two proteins interact
      predominantly in the cytoplasmic granules of cortical neurons in the human brain
      cortex. Based on this data, it can be concluded that Kiaa0319-like protein
      interacts with Nogo Receptor 1, supporting the idea that Kiaa0319-like protein
      participates in axon guidance.

PMID- 20697955
TI  - Glycosyl conjugates of biotinylated diaminopyridine applied for study of
      carbohydrate-to-carbohydrate interaction.
AB  - Previous studies by us and others established that cell-cell adhesion is mediated
      by specific carbohydrate-to-carbohydrate interaction (CCI). Those previous
      studies were based on various biochemical and biophysical approaches, including
      the use of labeled glycosyl epitopes with fluorescent tag. However, these methods
      ideally require that the glycosyl epitope must be fixed to a solid phase
      molecule, preferably with multivalency. The purpose of the present study is to
      establish a CCI process using specific glycosyl residues conjugated to
      biotinylated diaminopyridine (BAP), and to observe: (i) clear occurrence of
      homotypic CCI between "Os Fr.B" having 5-6 GlcNAc termini, vs. absence of such
      homotypic CCI between "Os Fr.1" having 2 GlcNAc termini; (ii) occurrence of
      heterotypic CCI between GM3 ganglioside and Os Fr.B, vs. absence of such
      heterotypic CCI between GM3 and Os Fr.1. Interaction between Os Fr.B-BAP
      conjugate and Os Fr.B-ceramide mimetic (Os Fr.B-mCer) was demonstrated based on
      two experiments: (i) dose-dependent binding of Os Fr.B-BAP conjugate to
      polystyrene plates coated with Os Fr.B-mCer was observed in the presence of
      bivalent cation, a prerequisite for all CCI processes, and such binding was
      abolished by EDTA; (ii) binding between equal nanomolar Os Fr.B-BAP and Os Fr.B
      mCer was inhibited by mM concentration Os Fr.B without conjugate, in dose
      dependent manner. Thus, cell adhesion processes based on homotypic CCI between N
      linked glycans having multiple GlcNAc termini, and heterotypic CCI between GM3
      and such glycans, were clearly observed using BAP conjugates of glycosyl
      epitopes.

PMID- 20697956
TI  - Thymoquinone-induced Neu4 sialidase activates NFkappaB in macrophage cells and
      pro-inflammatory cytokines in vivo.
AB  - Thymoquinone (TQ) derived from the nutraceutical black cumin oil has been
      reported to be a novel agonist of Neu4 sialidase activity in live cells
      (Glycoconj J DOI 10.1007/s10719-010-9281-6). The activation of Neu4 sialidase on
      the cell surface by TQ was found to involve GPCR-signaling via membrane targeting
      of Galphai subunit proteins and matrix metalloproteinase-9 activation. Contrary
      to other reports, TQ had no anti-inflammatory effects in vitro. Here, we show
      that MyD88/TLR4 complex formation and subsequent NFkappaB activation are induced
      by the Neu4 activity associated with TQ-stimulated live primary bone marrow (BM)
      macrophage cells from WT and Neu1-deficient mice, HEK-TLR4/MD2 cells and BMC-2
      macrophage cell line but not with primary macrophage cells from Neu4-knockout
      mice. Tamiflu (oseltamivir phosphate), pertussis toxin (PTX), a specific
      inhibitor of Galphai proteins of G-protein coupled receptor (GPCR) and the broad
      range inhibitor of matrix metalloproteinase (MMP) galardin applied to live
      primary BM macrophage cells completely block TQ-induced MyD88/TLR4 complex
      formation. Using immunocytochemistry and western blot analyses, Tamiflu, galardin
      and PTX inhibit NFkappaB activation induced by Neu4 activity associated with TQ
      stimulated BMC-2 cells, HEK-TLR4/MD2 cells and primary BM macrophages from WT
      mice. EMSA analyses on HEK-TLR4/MD2 nuclear cell extracts confirm the nuclear
      localization and DNA binding of TQ-induced NFkappaB activation in a biphasic
      manner within 30 min. Co-immunoprecipitation experiments reveal for the first
      time that MMP-9 may be an important intermediate link in the TQ-induced Neu4
      activity circuitously targeting TLR4 receptors. Central to this process is that
      Neu4 forms a complex with MMP-9, which is already bound to TLR4 receptors.
      Fluorescence spectrophotometer analyses of live CD14-THP1 cells treated with TQ
      show Neu4 sialidase activity over 5 min. Using flow cytometry analyses, CD14-THP1
      cells treated with TQ express stable protein levels of Neu4, TLR4 and MMP9 on the
      cell surface over 30 min except for a marked diminution of MMP9 at 15 min. Using
      cytokine array profiling analyses of serum, Neu4-knockout mice respond poorly to
      TQ in producing pro-inflammatory cytokines and chemokines after 5-h treatment
      compared to the wild-type or hypomorphic cathepsin A mice with a secondary 90%
      Neu1 deficient mice. Our findings establish an unprecedented signaling paradigm
      for TQ-induced Neu4 sialidase activity. It signifies that MMP-9 forms an
      important molecular signaling platform in complex with TLR4 receptors at the
      ectodomain and acts as the intermediate link for TQ-induced Neu4 sialidase in
      generating a functional receptor with subsequent NFkappaB activation and pro
      inflammatory cytokine production in vivo.

PMID- 20697957
TI  - Efficacy of an inactivated recombinant vaccine encoding a fimbrial protein of
      Pasteurella multocida B:2 against hemorrhagic septicemia in goats.
AB  - This study was carried out to determine the antibody responses and protective
      capacity of an inactivated recombinant vaccine expressing the fimbrial protein of
      Pasteurella multocida B:2 following intranasal vaccination against hemorrhagic
      septicemia in goats. Goats were vaccinated intranasal with 10(6) CFU/mL of the
      recombinant vaccine (vaccinated group) and 10(6) CFU/mL of pET32/LIC vector
      without fimbrial protein (control group). All three groups were kept separated
      before all goats in the three groups were challenged with 10(9) CFU/mL of live
      pathogenic P. multocida B:2. During the course of study, both serum and lung
      lavage fluid were collected to evaluate the antibody levels via enzyme-linked
      immunosorbent assay. It was found that goats immunized with the inactivated
      recombinant vaccine developed a strong and significantly (p < 0.05) higher
      specific IgA and IgG responses in both serum and lung lavage fluid samples
      compared to the control and unvaccinated groups. Following intratracheal
      challenge, the rate of isolation was 17% for the vaccinated group, 67% for the
      control group and 100% for the unvaccinated group. However, none of the goat from
      the vaccinated group had P. multocida B:2 in the liver, tonsil and heart.
      Therefore, the study revealed that an inactivated recombinant vaccine
      significantly provides significant protection against high dose challenge and
      enhances the stimulation of the local and systemic immunities.

PMID- 20697958
TI  - Frequency of extracolonic tumors in Brazilian families with Lynch syndrome:
      analysis of a hereditary colorectal cancer institutional registry.
AB  - Lynch syndrome (LS) is caused by inherited germline mutations in mismatch repair
      (MMR) genes. It is one of the commonest forms of inherited predisposition to
      colorectal cancer (CRC), accounting for 2-5% of all CRC. LS is characterized by
      early age of onset, with a tendency for multiplicity and an increased risk for
      extra-colonic tumors at particular sites. In this study we have evaluated the
      frequency of extra-colonic tumors in 60 unrelated LS families fulfilling the
      Amsterdam criteria (ACI. ACII) from the Oncotree database of the Hereditary
      Colorectal Cancer Registry of the AC Camargo Hospital. All families' pedigree was
      extensively analyzed, varying from 2 to 6 generations with a total of 2,095
      individuals evaluated. As expected, colorectal cancer was the most frequent tumor
      in the families (334 cases). We found 200 extracolonic tumors among all
      individuals with a higher ratio in women (123 cases) than men (77 cases). By far,
      breast cancer (32 cases) was the most frequent extracolonic manifestation in
      women followed by endometrial (20 cases) and uterine cervix cancer (20 cases).
      For man, prostate (16 cases) and stomach (12 cases) cancer were the most frequent
      extracolonic tumors. It is well know that establishing the diagnosis is
      challenging and requires knowledge and surveillance. Thus, recognition of
      individuals and families with hereditary predisposition to cancer according to
      clinical and molecular features, combined with intensive surveillance and
      management programs, can contribute substantially to improve results related to
      the diagnosis and characterization of LS.

PMID- 20697960
TI  - Race, disadvantage and faculty experiences in academic medicine.
AB  - BACKGROUND: Despite compelling reasons to draw on the contributions of under
      represented minority (URM) faculty members, US medical schools lack these
      faculty, particularly in leadership and senior roles. OBJECTIVE: The study's
      purpose was to document URM faculty perceptions and experience of the culture of
      academic medicine in the US and to raise awareness of obstacles to achieving the
      goal of having people of color in positions of leadership in academic medicine.
      DESIGN: The authors conducted a qualitative interview study in 2006-2007 of
      faculty in five US medical schools chosen for their diverse regional and
      organizational attributes. PARTICIPANTS: Using purposeful sampling of medical
      faculty, 96 faculty were interviewed from four different career stages (early,
      plateaued, leaders and left academic medicine) and diverse specialties with an
      oversampling of URM faculty. APPROACH: We identified patterns and themes emergent
      in the coded data. Analysis was inductive and data driven. RESULTS: Predominant
      themes underscored during analyses regarding the experience of URM faculty were:
      difficulty of cross-cultural relationships; isolation and feeling invisible; lack
      of mentoring, role models and social capital; disrespect, overt and covert
      bias/discrimination; different performance expectations related to
      race/ethnicity; devaluing of research on community health care and health
      disparities; the unfair burden of being identified with affirmative action and
      responsibility for diversity efforts; leadership's role in diversity goals; and
      financial hardship. CONCLUSIONS: Achieving an inclusive culture for diverse
      medical school faculty would help meet the mission of academic medicine to train
      a physician and research workforce that meets the disparate needs of our
      multicultural society. Medical school leaders need to value the inclusion of URM
      faculty. Failure to fully engage the skills and insights of URM faculty impairs
      our ability to provide the best science, education or medical care.

PMID- 20697961
TI  - Hospital-based comparative effectiveness centers: translating research into
      practice to improve the quality, safety and value of patient care.
AB  - Hospital-based comparative effectiveness (CE) centers provide a model that
      clinical leaders can use to improve evidence-based practice locally. The model is
      used by integrated health systems outside the US, but is less recognized in the
      US. Such centers can identify and adapt national evidence-based policies for the
      local setting, create local evidence-based policies in the absence of national
      policies, and implement evidence into practice through health information
      technology (HIT) and quality initiatives. Given the increasing availability of CE
      evidence and incentives to meaningfully use HIT, the relevance of this model to
      US practitioners is increasing. This is especially true in the context of
      healthcare reform, which will likely reduce reimbursements for care deemed
      unnecessary by published evidence or guidelines. There are challenges to
      operating hospital-based CE centers, but many of these challenges can be overcome
      using solutions developed by those currently leading such centers. In conclusion,
      these centers have the potential to improve the quality, safety and value of care
      locally, ultimately translating into higher quality and more cost-effective care
      nationally. To better understand this potential, the current activity and impact
      of hospital-based CE centers in the US should be rigorously examined.

PMID- 20697962
TI  - From the editors' desk: confronting costs of care at the end of life.

PMID- 20697963
TI  - Efficacy and safety of tunneled pleural catheters in adults with malignant
      pleural effusions: a systematic review.
AB  - BACKGROUND: Malignant pleural effusions (MPE) are a frequent cause of dyspnea and
      discomfort at the end of cancer patients' lives. The tunneled indwelling pleural
      catheter (TIPC) was approved by the FDA in 1997 and has been investigated as a
      treatment for MPE. OBJECTIVE: To systematically review published data on the
      efficacy and safety of the TIPC for treatment of MPE. DESIGN: We searched the
      MEDLINE, EMBASE, and ISI Web of Science databases to identify studies published
      through October 2009 that reported outcomes in adult patients with MPE treated
      with a TIPC. Data were aggregated using summary statistics when outcomes were
      described in the same way among multiple primary studies. MAIN MEASURES:
      Symptomatic improvement and complications associated with use of the TIPC. KEY
      RESULTS: Nineteen studies with a total of 1,370 patients met criteria for
      inclusion in the review. Only one randomized study directly compared the TIPC
      with the current gold standard treatment, pleurodesis. All other studies were
      case series. Symptomatic improvement was reported in 628/657 patients (95.6%).
      Quality of life measurements were infrequently reported. Spontaneous pleurodesis
      occurred in 430/943 patients (45.6%). Serious complications were rare and
      included empyema in 33/1168 patients (2.8%), pneumothorax requiring a chest tube
      in 3/51 (5.9%), and unspecified pneumothorax in 17/439 (3.9%). Minor
      complications included cellulitis in 32/935 (3.4%), obstruction/clogging in
      33/895 (3.7%) and unspecified malfunction of the catheter in 11/121 (9.1%). The
      use of the TIPC was without complication in 517/591 patients (87.5%).
      CONCLUSIONS: Based on low-quality evidence in the form of case series, the TIPC
      may improve symptoms for patients with MPE and does not appear to be associated
      with major complications. Prospective randomized studies comparing the TIPC to
      pleurodesis are needed before the TIPC can be definitively recommended as a first
      line treatment of MPE.

PMID- 20697964
TI  - Assessing coronary risk assessment: what's next?

PMID- 20697965
TI  - What happens after an elevated PSA test: the experience of 13,591 veterans.
AB  - BACKGROUND: The occurrence and timing of prostate biopsy following an elevated
      prostate-specific antigen (PSA) test varied considerably in randomized screening
      trials. OBJECTIVE: Examine practice patterns in routine clinical care in response
      to an elevated PSA test (>=4 ng/MUl) and determine whether time to biopsy was
      associated with cancer stage at diagnosis. DESIGN: Retrospective cohort study.
      PARTICIPANTS: All veterans (n=13,591) in the Pacific Northwest VA Network with a
      PSA >=4 ng/MUl between 1998 and 2006 and no previous elevated PSA tests or
      prostate biopsy. MAIN MEASURES: We assessed follow-up care including additional
      PSA testing, urology consults, and biopsies. We compared stage at diagnosis for
      men who were biopsied within 24 months vs. those men biopsied and diagnosed>24
      months after the elevated PSA test. KEY RESULTS: Two-thirds of patients received
      follow-up evaluation within 24 months of the elevated PSA test: 32.8% of men
      underwent a biopsy, 15.5% attended a urology visit but were not biopsied, and
      18.8% had a subsequent normal PSA test. Younger age, higher PSA levels, more
      prior PSA tests, no co-payment requirements, existing urologic conditions, low
      body mass index, and low comorbidity scores were associated with more complete
      follow-up. Among men who underwent radical prostatectomy, a delayed diagnosis was
      not significantly associated with having a pathologically advanced-stage cancer
      (T3/T4), although we found an increased likelihood of presenting with stage T2C
      relative to stage T2A or T2B cancer. CONCLUSIONS: Follow-up after an elevated PSA
      test is highly variable with more than a third of men receiving care that could
      be considered incomplete. A delayed diagnosis was not associated with poorer
      prognosis.

PMID- 20697966
TI  - Fulminant, non-antibiotic associated Clostridium difficile colitis following
      Salmonella gastroenteritis.
AB  - In the last decade there has been increasing awareness of the virulence and
      changing epidemiology of Clostridium difficile (C. difficile). While the vast
      majority of clinical cases of C. difficile are associated with antimicrobial or
      nosocomial exposure, this syndrome has been well described in the absence of
      antibiotic use. We present an unusual case of fatal, non-antibiotic associated C.
      difficile colitis following Salmonella serotype Saintpaul gastroenteritis in a
      previously healthy young person. We review the typical risk factors for C.
      difficile colitis and fulminant disease. We also review the epidemiology of
      community-acquired C. difficile-associated disease (CA-CDAD) and highlight
      Salmonella infection as a potential risk factor for development of CA-CDAD.

PMID- 20697967
TI  - The effect of workload reduction on the quality of residents' discharge
      summaries.
AB  - BACKGROUND: The completeness of hospital discharge summaries may reflect the
      overall quality of inter-professional communications. The effect of reducing
      resident workload on clinical performance is largely unknown. OBJECTIVE: We
      examined the impact of reducing housestaff workload on the quality of discharge
      summaries, an indicator of clinical performance, as compared to discharge
      summaries created by trainees on a team with a more typical workload. DESIGN:
      Patients admitted to a medicine service at a community teaching hospital
      affiliated with an academic medical center were alternately allocated between a
      control and intervention care team of residents. First-year residents on the
      intervention team carried an average census of 3.5 patients compared with 6.6
      patients for peers on the control team. A random selection of 142 discharge
      summaries from a 3-month period were blindly evaluated using a structured tool
      based on professional documentation standards. PARTICIPANTS: 61 internal medicine
      residents. MAIN RESULTS: Inter-rater reliability of discharge summary quality was
      0.9. Discharge summaries produced by residents on the intervention team with a
      reduced workload had significantly more of the required elements (74 vs 65%,
      p<0.001). Intervention team summaries were more frequently complete and contained
      significantly more of the required elements describing the patient history (65.7%
      vs 36.1%, p=0.0005), the inpatient narrative (47.1% vs 22.2%, p=0.003), discharge
      planning (20.0% vs 5.5%, p=0.012), and continuity of care (24.3% vs 6.9%,
      p=0.005). Fewer than a quarter of the summaries reviewed included discharge
      instructions, information on follow-up care, or a discharge medication list.
      CONCLUSIONS: Reducing resident workload can significantly improve discharge
      summary quality, a measure of resident performance.

PMID- 20697968
TI  - Primary care and the US health care system: what needs to change?

PMID- 20697969
TI  - Becoming a father.

PMID- 20697970
TI  - Up close and personal.

PMID- 20697972
TI  - Final moments.

PMID- 20697973
TI  - First night on call in emergency psychiatry.

PMID- 20697971
TI  - Update in addiction medicine for the generalist.

PMID- 20697974
TI  - Adding new tools to the black bag--introduction of ultrasound into the physical
      diagnosis course.
AB  - INTRODUCTION: Ultrasound, a versatile diagnostic modality that permits real-time
      visualization at the patient's bedside, can be used as an adjunct in teaching
      physical diagnosis (PD). AIMS: (1) to study the feasibility of incorporating
      ultrasound into PD courses and (2) determine whether learners can demonstrate
      image recognition and acquisition skills. PROGRAM DESCRIPTION: Three hundred
      seven second-year medical students were introduced to cardiovascular and
      abdominal ultrasound scanning after training in the physical examination. This
      consisted of a demonstration of the ultrasound examination, followed by practice
      on standardized patients (SPs). Pre-post tests were administered to evaluate
      students' knowledge and understanding of ultrasound. Students performed an
      ultrasound examination during the PD final examination. PROGRAM EVALUATION: Pre
      post test data revealed significant improvements in image recognition. On the
      final exam, the highest scores (98.4%) were obtained for the internal jugular
      vein and lowest scores (74.6%) on the Focused Assessment with Sonography for
      Trauma images. Eighty-nine percent of students' surveyed felt ultrasound was a
      valuable tool for physicians. DISCUSSION: An introductory ultrasound course is
      effective in improving medical students' acquisition and recognition of basic
      cardiovascular and abdominal ultrasound images. This innovative program
      demonstrates the feasibility of incorporating portable ultrasound as a learning
      tool during medical school.

PMID- 20697975
TI  - An electrophysiological study of acute tetrodotoxin poisoning.
AB  - To evaluate the electrophysiological changes in patients with acute tetrodotoxin
      (TTX) poisoning from ingestion of globefish (Tetraodontidae) patients exposed to
      TTX were compared with age-matched controls. The cohort of TTX-poisoning cases
      was clinically subdivided into mild, moderate, or severe cases. The motor nerve
      conduction velocity (MCV), sensory nerve conduction velocity (SCV), F-wave, H
      reflex, and somatosensory-evoked potentials (SEP) of the median, ulnar, and
      common peroneal nerve (CPN) were determined using established techniques. Four of
      the 64 (6.3%) TTX-poisoning cases died and were omitted from the final analysis.
      The MCV and SCV of the median, ulnar, and CPN nerves in all the TTX-poisoning
      cases were significantly slower than the healthy controls. Severe cases of TTX
      poisoning had more significant reduction in nerve function. Thus,
      electroneurophysiological analysis could be used to determine the extent, course,
      and range of nerve system damage in patients with acute TTX poisoning.

PMID- 20697976
TI  - Effects of menadione, hydrogen peroxide, and quercetin on apoptosis and delayed
      luminescence of human leukemia Jurkat T-cells.
AB  - Menadione (MD) is an effective cytotoxic drug able to produce intracellularly
      large amounts of superoxide anion. Quercetin (QC), a widely distributed
      bioflavonoid, can exert both antioxidant and pro-oxidant effects and is known to
      specifically inhibit cell proliferation and induce apoptosis in different cancer
      cell types. We have investigated the relation between delayed luminescence (DL)
      induced by UV-laser excitation and the effects of MD, hydrogen peroxide, and QC
      on apoptosis and cell cycle in human leukemia Jurkat T-cells. Treatments with 500
      MUM H2O2 and 250 MUM MD for 20 min produced 66.0 +/- 4.9 and 46.4 +/- 8.6%
      apoptotic cell fractions, respectively. Long-term (24 h) pre-exposure to 5 MUM,
      but not 0.5 MUM QC enhanced apoptosis induced by MD, whereas short-term (1 h) pre
      incubation with 10 MUM QC offered 50% protection against H2O2-induced apoptosis,
      but potentiated apoptosis induced by MD. Since physiological levels of QC in the
      blood are normally less than 10 MUM, these data can provide relevant information
      regarding the benefits of flavonoid-combined treatments of leukemia. All the
      three drugs exerted significant effects on DL. Our data are consistent with (1)
      the involvement of Complex I of the mitochondrial respiratory chain as an
      important source of delayed light emission on the 10 MUs-10 ms scale, (2) the
      ability of superoxide anions to quench DL on the 100 MUs-10 ms scale, probably
      via inhibition of reverse electron transfer at the Fe/S centers in Complex I, and
      (3) the relative insensitivity of DL to intracellular OH* and H2O2 levels.

PMID- 20697977
TI  - Effects of microgravity modeled by large gradient high magnetic field on the
      osteogenic initiation of human mesenchymal stem cells.
AB  - Microgravity (MG) leads to a decrease in osteogenic potential of human bone
      marrow-derived mesenchymal stem cells (hMSCs). In the present study, we used
      large gradient high magnetic field (LGHMF) produced by a superconducting magnet
      to model MG (LGHMF-MG) and analyzed the effects of LGHMF-MG on survival,
      cytoskeleton and osteogenic potential of hMSCs. Results showed that the LGHMF-MG
      treatment for 6 h disrupted the cytoskeleton of hMSCs, and the LGHMF-MG treatment
      for 24 h led to cell death. LGHMF-MG treatments for 6 h in early stages of
      osteogenic induction (the pre-treatment before osteogenic induction, the
      beginning-treatment in the beginning-stage of osteogenic induction and the middle
      treatment in the middle-stage of osteogenic induction) resulted in suppression on
      osteogenesis of hMSCs. The suppression intensity was reduced gradually as the
      treatment stage of LGHMF-MG was postponed. The LGHMF-MG treatment for 6 h in the
      ending-stage of osteogenic induction (the ending-treatment) had no obvious effect
      on osteogenesis of hMSCs. These results indicated that LGHMF-MG should affect the
      initiation of osteogenesis. Finally, the possible mechanism for the inhibition
      effect of LGHMF-MG on osteogenesis of hMSCs is discussed.

PMID- 20697978
TI  - In silico analyses of proteomic data suggest a role for heat shock proteins in
      umbilical cord blood hematopoietic stem cells.
AB  - Umbilical-cord blood (UCB) has growingly become an accepted alternative source of
      hematopoietic stem cells for transplantation purposes. However, the low cell dose
      limit within a single unit is still an obstacle hindering the way of a broader
      diffusion. The real deal is the lack of knowledge about the molecular processes
      governing the events of expansion and differentiation of these cells. In order to
      fill this void, several studies were focused on the identification of the
      peculiar whole protein profile of UCB-derived hematopoietic stem cells. In this
      review article we provide a referenced list of overall proteins from UCB-derived
      hematopoietic stem and progenitor cells. This list has been elaborated for
      pathway and network analyses, along with GO term enrichment for biological and
      molecular functions, in order to individuate main classes of proteins governing
      functioning of these cells. From these analyses it seems to emerge a central role
      for heat shock proteins in immature hematopoietic stem cells. Their role might be
      relevant in protecting crucial transcription factors which drive proliferation
      and differentiation towards a specific lineage (e.g. erythroid, myeloid). Hereby
      we also stress the helpfulness of interactomics elaboration in providing a
      unified overview of independent proteomics data. It appears that maturation,
      other than representing a bottleneck to protein expression, could sculpt
      interaction maps via reducing complexity of immature interactomics profiles.

PMID- 20697979
TI  - Glioma stem/progenitor cells contribute to neovascularization via
      transdifferentiation.
AB  - OBJECTIVE: Previous studies suggest that tumor cells might be the progenitor for
      tumor vasculature. Whether vascular tube formation from transdifferentiation of
      human glioma stem/progenitor cells (hGSPCs) contribute to angiogenesis of gliomas
      remain largely uncertain. METHODS: hGSPCs were isolated from thirteen surgical
      specimens of gliomas and cultured in medium favored for stem cell growth. In
      vitro transdifferentiation of hGSPCs was performed under hypoxia. Expression of
      vascular endothelial cells (VECs) markers CD31, CD34, kinase insert domain
      receptor (KDR), and von Willebrand factor (vWF) were analyzed with real-time
      quantitative RT-PCR and immunofluorescence techniques. Vasculogenic mimicry of
      hGSPCs was evaluated in a tumor stem cell xenograft model in vivo. Relationships
      between content of hGSPCs and expression levels of both VECs markers and
      proangiogenic factors in large number of clinical specimens were further
      investigated in glioma tissue microarray. RESULTS: In vitro, hGSPCs can
      transdifferentiate into VECs under hypoxia, they manifested typical "flagstone"
      pattern when cultivated in medium containing VEGF for a few days; when cultivated
      on Matrigel they were capable of forming capillary-like structures. Expression of
      VECs markers including CD31, CD34, KDR, and vWF were significantly up-regulated
      after transdifferentiation. Human leukocyte antigen (HLA) positively stained
      vessels were observed inside the xenograft tumors after intracerebral
      transplantation of hGSPCs in athymic nude mice, implied part of tumor cells with
      human origin were involved in formation of tumor vessels. In surgical specimens
      of human glioma, tumor vascular cells coexpressing the markers of early VECs
      (CD34) and markers of hGSPCs (ABCG2 and nestin) suggest that these vascular cells
      may stemmed from hGSPCs. CONCLUSIONS: Our observations suggest the functional
      role of hGSPCs as endothelial progenitors, which have properties that give rise
      to VECs, and have the ability to form vascular endothelial tubes. However,
      unspecific markers (ABCG2, nestin) that stain for both endothelial as well as
      glioma stem cells, were found to be expressed in tumor vasculature of human
      specimen, and limit further interpretation of this finding.

PMID- 20697980
TI  - Neurologic consequences of the immune reconstitution inflammatory syndrome
      (IRIS).
AB  - Although major advancements have been made in the treatment of HIV infection,
      graft-versus-host reactions, and autoimmune diseases, an unexpected consequence
      of treatment has been the emergence of a devastating inflammatory syndrome,
      termed the immune reconstitution inflammatory syndrome (IRIS). The
      pathophysiology of the syndrome is poorly understood, and the syndrome poses
      unique challenges for diagnosis and treatment. We have reviewed the neurologic
      manifestations of IRIS in the context of HIV infection as well as in the setting
      of treatment of autoimmune diseases such as multiple sclerosis, in which
      compartmental immune suppression may occur without an obvious underlying immune
      suppression. The purpose of this review is to identify common themes that may
      assist in the diagnosis and management of these IRIS syndromes.

PMID- 20697981
TI  - Ocular motility of aging and dementia.
AB  - Visual complaints in patients with dementia are varied and attributable to both
      visual sensory (afferent) and ocular motor (efferent) dysfunction. This review
      focuses exclusively on the efferent visual dysfunction associated with dementia
      and aging. It provides a brief overview of the most common ocular motility
      disturbances associated with dementia, including Alzheimer's disease, Parkinson's
      disease, diffuse Lewy body disease, corticobasal syndrome, progressive
      supranuclear palsy, frontotemporal lobar degeneration, Creutzfeldt-Jakob disease,
      and others. An introduction to the six eye movement systems and the terminology
      associated with the evaluation of each system are reviewed. Assessment of
      efferent visual function in patients with dementia may be challenging, but
      familiarity with the potential pathologic eye movement findings in patients with
      dementia will allow for a focused assessment, diagnosis, and treatment when
      possible.

PMID- 20697982
TI  - Neurologic and muscular complications of the 2009 influenza A (H1N1) pandemic.
AB  - In the spring of 2009 a new triple-reassortant of influenza A (H1N1) virus
      appeared in Mexico and rapidly spread around the world, becoming a pandemic that
      primarily infected children and uncommonly older adults. Accompanying the
      pandemic were associated neurologic and muscular syndromes that affected
      primarily children and included febrile seizures, encephalopathy/encephalitis
      with or without seizures, delirium, focal neurologic syndromes, Guillain-Barre
      syndrome, myositis, and myocarditis. Neither the frequency nor the severity of
      these syndromes appears different from those recognized during periods of
      infections of previous influenza A viruses. I review the clinical, laboratory,
      neuroimaging, and pathologic characteristics of the associated syndromes
      appearing in the first wave of the pandemic, compare them to similar cases
      occurring in previous years, and explore several theories of pathogenesis.

PMID- 20697983
TI  - Remission in rheumatoid arthritis.
AB  - With advancing therapeutic options, achieving a state of remission has become the
      treatment goal in rheumatoid arthritis. Agreeing on what constitutes remission
      and what measures should be used to assess disease activity has remained a
      challenge. Multiple remission criteria have been devised and modified, all with
      different strengths and limitations. A consensus definition of remission will
      need to be achieved if we are to be able to evaluate outcomes of clinical trials
      and establish treatment targets for practice. Remission defined as the complete
      absence of disease currently may not be a realistic therapeutic goal.

PMID- 20697984
TI  - Formulation and in vitro characterization of Eudragit(r) L100 and Eudragit(r)
      L100-PLGA nanoparticles containing diclofenac sodium.
AB  - The aim of this study was to formulate and characterize Eudragit(r) L100 and
      Eudragit(r) L100-poly(lactic-co-glycolic acid) (PLGA) nanoparticles containing
      diclofenac sodium. Diclofenac generates severe adverse effects with risks of
      toxicity. Thus, nanoparticles were prepared to reduce these drawbacks in the
      present study. These nanoparticles were evaluated for surface morphology,
      particle size and size distribution, percentage drug entrapment, and in vitro
      drug release in pH 6.8. The prepared nanoparticles were almost spherical in
      shape, as determined by atomic force microscopy. The nanoparticles with varied
      size (241-274 nm) and 25.8-62% of entrapment efficiency were obtained. The
      nanoparticles formulations produced the release profiles with an initial burst
      effect in which diclofenac sodium release ranged between 38% and 47% within 4 h.
      The extent of drug release from Eudragit(r) L100 nanoparticles was up to 92% at
      12 h. However, Eudragit(r)/PLGA nanoparticles showed an initial burst release
      followed by a slower sustained release. The cumulative release at 72 h was 56%,
      69%, and 81% for Eudragit(r)/PLGA (20:80), Eudragit(r)/PLGA (30:70) and
      Eudragit(r)/PLGA (50:50) nanoparticles, respectively. The release profiles and
      encapsulation efficiencies depended on the amount of Eudragit in the blend. These
      data demonstrated the efficacy of these nanoparticles in sustaining the
      diclofenac sodium release profile.

PMID- 20697985
TI  - Left ventricular hypertrophy induced by abdominal aortic banding and its
      prevention by angiotensin receptor blocker telmisartan--a proteomic analysis.
AB  - Cardiac hypertrophy is frequently caused by pressure overload (i.e., high blood
      pressure or hypertension) and can lead to heart failure. The major objective of
      the present study was to investigate the proteomic changes in response to the
      development of left ventricular hypertrophy (LVH) induced by abdominal aortic
      banding (AB) and its prevention by antihypertensive treatment with angiotensin II
      receptor blocker (ARB) telmisartan. One week after AB and Sham surgery, rats were
      assigned into three groups: SHAM-control, aortic banding without treatment (AB
      Ctrl) and aortic banding with telmisartan treatment (AB-Telmi; 5mg/kg/day for 8
      weeks). Echocardiography, hemodynamics, and pathology were performed to assess
      LVH. Left ventricular myocardium was sampled. The analysis of proteomic proteins
      from myocardium was performed by two-dimensional gel electrophoresis and MALDI
      TOF-MS. In AB-Ctrl, heart rate, systolic arterial blood pressure, diastolic blood
      pressure, left ventricular end systolic pressure, interventricular septal
      thickness at diastole, posterior wall thickness in diastole, heart weight (HW)
      and HW/body weight (BW) were increased, indicating that both hypertension and LVH
      developed. Telmisartan prevented hypertension and LVH. Concurrently, among
      numerous proteins, there were 17 that were differentially expressed among
      hypertrophic hearts, normal hearts, and the hearts where hypertrophic response
      was suppressed by ARB treatment. Primarily, proteins involved in cell structure,
      metabolism, stress and signal transduction exhibited up-regulations in LVH,
      providing cellular and molecular mechanism for hypertrophic development. These
      changes were prevented or greatly attenuated by telmisartan regimen.
      Interestingly, antioxidative-related heat shock protein 2 was detected neither in
      SHAM-Ctrl nor in AB-Ctrl, but in AB-Telmi. LVH is accompanied by series changes
      of protein expression. Both LVH and proteomic changes can be prevented by
      blockade of renin-angiotensin system with telmisartan. These protein alterations
      may constitute mechanistic pathways leading to hypertrophy development and
      experimental targets for novel therapeutic strategy.

PMID- 20697986
TI  - Clinical presentation of carcinoma of unknown primary: 14 years of experience.
AB  - A carcinoma of unknown primary (CUP) is a histologically confirmed metastatic
      cancer without a definitive primary site after performing a detailed medical
      examination. The purpose of the study was to classify unfavorable CUPs into more
      reliable disease entities, which reflect the clinical course. We reviewed the
      medical records of patients diagnosed with a CUP between January 1995 and March
      2008. Patients were classified into a conventional favorable-risk group and a
      newly proposed unfavorable-risk group according to the clinicopathologic
      features. Five hundred eighty-six patients were diagnosed with CUPs. Fifty-six
      (9.6%) patients were classified in the conventional favorable-risk group, and 486
      (82.9%) patients were classified in the unfavorable-risk group. We further
      classified the 486 patients into six subgroups with an unfavorable risk, while
      excluding 29 patients (5.0%) who were not classifiable. The overall survival of
      the conventional favorable-risk group was 47.0 months (95% CI, 11.1~82.9 months),
      which was significantly longer than that of any subgroup of the newly proposed
      unfavorable-risk group (P < 0.001). Patients with squamous cell carcinoma in the
      abdominopelvic cavity showed similar overall survival with unfavorable-risk group
      (P = 0.484). Women with non-papillary malignant ascites had a survival in between
      the favorable and unfavorable groups (P <  0.001). The newly proposed unfavorable
      risk group may assist in classifying CUP patients with an unfavorable risk in a
      clinically more meaningful way. Squamous cell carcinoma in the abdominopelvic
      cavity should be considered in the unfavorable-risk group and women with non
      papillary malignant ascites in an intermediate-risk group. Further studies with
      molecular profiling would help in classifying and treating patients with CUPs and
      an unfavorable risk.

PMID- 20697987
TI  - Clinical significance of Maspin promoter methylation and loss of its protein
      expression in invasive ductal breast carcinoma: correlation with VEGF-A and MTA1
      expression.
AB  - Maspin is a serine protease inhibitor with tumor-suppressor activity. Maspin can
      suppress tumor growth and metastasis in vivo and tumor cell motility and invasion
      in vitro. Previous studies indicate that the loss of Maspin expression is closely
      linked to aberrant methylation of the Maspin promoter. We examined the promoter
      methylation status of Maspin in tumor and corresponding serum of breast cancer
      patients. In addition, protein expression of this gene was also assessed to
      determine possible correlation between promoter hypermethylation and gene
      silencing. Further, we investigated the correlation of Maspin expression with
      vascular endothelial growth factor (VEGF-A) and MTA1 expression. Maspin
      methylation was analyzed by methylation-specific PCR in 100 invasive ductal
      breast carcinoma patients' tumors and circulating DNA in a prospective study.
      Promoter hypermethylation was correlated with expression of the encoded protein
      in tumors by immunohistochemistry. Significant correlation was observed between
      promoter hypermethylation of Maspin (r = +0.88; p <= 0.0001) in tumors and paired
      sera. Significant association was found between Maspin promoter hypermethylation
      and loss of its protein expression (p = 0.01, OR = 3.1, 95% CI = 1.3-7.4). The
      expression of VEGF-A and MTA1 was lower in tumors with high Maspin expression
      compared to tumors with loss of Maspin expression. Our results indicate that
      aberrant promoter methylation is associated with loss of Maspin immunoreactivity
      in breast cancer tissues. Further, loss of Maspin expression is significantly
      correlated with increased expression of VEGF-A and MTA1.

PMID- 20697988
TI  - [Current developments in psychotherapy training].

PMID- 20697989
TI  - [Power, p-value, and sample size].

PMID- 20697990
TI  - Facial nerve reconstruction using a vascularized lateral femoral cutaneous nerve
      graft based on the superficial circumflex iliac artery system: an application of
      the inferolateral extension of the groin flap.
AB  - The use of an inferolateral extension technique of a groin flap has previously
      been reported. This technique involves harvesting an extended portion from the
      anterolateral thigh, including the lateral femoral cutaneous nerve (LFCN) and its
      accompanying vessels, attached to a groin flap via communications between the
      LFCN-accompanying vessels and the superficial circumflex iliac artery (SCIA)
      system. In this study, we used this technique involving a vascularized LFCN
      combined with a groin flap to reconstruct a facial nerve defect. The patient was
      a 58-year-old man with a salivary duct carcinoma in the left parotid gland. Tumor
      ablation resulted in a defect of the skin and soft tissue including all branches
      of the facial nerve. A free groin flap was harvested based on the SCIA system,
      composed of the LFCN and a small monitoring flap, which were nourished by the
      LFCN-accompanying vessels and by communication with the SCIA system. The LFCN was
      transplanted into the gaps in the facial nerve branches as a cable graft, and the
      skin flap was used to cover and fill the soft tissue defect. The postoperative
      course was uneventful and satisfactory facial animation was obtained. This
      represents a possible technique for nerve reconstruction using a vascularized
      nerve graft.

PMID- 20697991
TI  - Use of an extracorporeal membrane oxygenation circuit as a bridge to salvage a
      major upper-extremity replant in a critically ill patient.
AB  - Major replantation of the upper extremity is defined as replantation at or above
      the level of the wrist. Selection of appropriate candidates is complex and
      requires consideration of many patient- and injury-associated factors including
      patient age, associated injuries, patient desire, mechanism of injury, ischemia
      time, wound condition, and presence of multiple-level injury. With respect to
      age, younger patients, especially children, are deemed to have a distinct
      advantage over more elderly patients due to improved nerve regeneration, and many
      advocate making every effort to replant this population. The risks of major upper
      extremity replantation are significant and include bleeding, depletion of
      coagulation factors, secondary infection, and sepsis. As a result, major systemic
      illness and significant associated injuries are accepted as contraindications to
      limb salvage in this patient population. Herein we describe the use of an
      extracorporeal membrane oxygenation (ECMO) circuit as a potential bridge for
      short-term preservation of the extremity in a young patient with an acute,
      concomitant systemic illness. In the authors' opinion, use of ECMO perfusion is a
      viable means of maintaining extremity perfusion over hours or even days and may
      lead to broadened replant criteria in patients with associated injuries.

PMID- 20697992
TI  - Microvascular reconstruction of composite cranial defects.
AB  - Microvascular reconstruction of composite cranium defects is challenging, and
      operative planning differs in various anatomic regions of the cranium. The aim of
      this article is to detail surgical strategies for microvascular reconstruction in
      different areas of the cranium. Fifty-eight free tissue transfers were performed
      in 54 patients with composite cranial defects between 1995 and 2009. The cranium
      was divided into six zones to classify the defects. Data on patient demographics,
      location and cause of the defects, technical details of surgical management, and
      complications were analyzed. Defects were secondary to ablative procedures in 45
      patients. Eight patients had posttraumatic defects, and one patient had
      congenital defect. Nine different flap types were used in the series. Choice of
      recipient vessels and the use of interpositional vein grafts varied according to
      the site of the cranial defects. Microsurgical reconstruction of cranial defects
      can be performed safely with predictable outcome by methodic assessment of the
      problem and by careful attention to the details of the reconstructive plan. In
      this article, valid conclusions on the planning of microvascular reconstruction
      in different areas of the cranium have been determined.

PMID- 20697993
TI  - [Last neuro-psychiatrist erased].

PMID- 20697994
TI  - [A multi-centre study of the reliability, validity and sensitivity to change of
      the honos65+ in psychiatry for older persons].
AB  - BACKGROUND: Within the mental health care services for older persons there is a
      growing need for insight into and evaluation of the results of clinical
      treatment. The Health of the Nations Outcome Scales 65+ (honos65+) is a promising
      instrument for the assessment of mental, social and physical health in older
      persons, but it is not yet known whether it is valid for older persons in the
      Netherlands. AIM: To assess the reliability, validity and sensibility to change
      of the honos65+ when applied to older persons with psychiatric disorders. METHOD:
      The bio-psycho-social level of functioning of clients aged 60 and over (n=168)
      receiving mental health care was assessed by means of existing and validated
      measuring instruments and the results were compared with those obtained with the
      honos65+. Three months later the population sample was re-assessed in order to
      test the extent to which the honos65+ was sensitive to change. RESULTS: The
      reliability and validity of the honos65+ could be ascertained for 168 clients
      aged 60 and over. After three months 116 clients were re-assessed so that the
      sensitivity of the honos65+ to change could be noted. CONCLUSION: The honos65+ is
      a reliable and valid instrument for assessing clients with affective disorders
      such as depression and anxiety and for detecting changes in clients' problems and
      functioning. No conclusions could be reached regarding the reliability and
      validity of the honos65+ when used for clients with other psychiatric disorders
      because the clinical subgroups were too small for patterns to be detected.

PMID- 20697995
TI  - [Fitness to drive in psychiatric patients; a review of the literature and
      consequences for daily practice].
AB  - BACKGROUND: A question that often arises in daily practice is whether a
      psychiatric patient should be considered as still fit to drive. AIM: To describe
      the Dutch regulations concerning psychiatric patients' fitness to drive and to
      evaluate the scientific basis of these regulations. METHOD: Information about the
      current regulations was collected and summarised and the specialist literature
      was reviewed. RESULTS: The regulations in the Netherlands are rather strict and
      as a result persons with a psychiatric illness can sometimes have their driving
      license withdrawn for a long period. The literature that was reviewed reveals
      that there is much uncertainty concerning the relationship between psychiatric
      illness and its effects on fitness to drive. CONCLUSION: The specialist
      literature indicates that some of the Dutch regulations are unfair and too rigid.
      In this article the consequences for daily practice are considered and a plea is
      made for more research and for laws and regulations that have a more solid basis.

PMID- 20697996
TI  - [The therapeutic value of physical exercise for people with schizophrenia].
AB  - BACKGROUND: Only about 25% of people with schizophrenia follow the public health
      recommendations for a minimum of 150 minutes per week of moderate physical
      exercise. In their leisure time people diagnosed with schizophrenia take
      considerably less exercise than their healthy counterparts. AIM: To collect
      scientific evidence of movement-related interventions in patients with
      schizophrenia. METHOD: PubMed, PEDro, CINAHL, PsychINFO and Sport Discus were
      searched for the period from 2003 up to April 2009 for reports of randomised
      controlled trials (RCTs) on the basis of the search terms 'schizophrenia',
      'exercise' and 'physical activity'. Relevant literature was also traced by means
      of the reference lists for selected articles. RESULTS: Eight RCTs were selected.
      Physical exercise was reported to bring about significant improvements in
      cardiovascular and metabolic parameters and in psychiatric symptomatology. A
      physical exercise also has social advantages; it helps patients to cope with
      stress and improves their quality of life. CONCLUSION: Physical exercise as part
      of psychomotor therapy should play an important role within the multidisciplinary
      treatment of schizophrenia. More research is needed into the effect of physical
      activity on cognitive functioning.

PMID- 20697997
TI  - [Is it acceptable to use placebos in depression research?].
AB  - The use of placebos in an investigation into the efficacy of a new type of
      treatment for winter depression was not approved by a medical ethics committee
      because some test subjects receiving placebos might thereby be deprived of an
      effective treatment. According to the authors, the committee's decision
      constituted an impediment to research and prevented a thorough investigation of a
      possible new type of treatment. In this essay it is argued that the use of
      placebos in depression research is ethically acceptable.

PMID- 20697998
TI  - [Melancholia, psychomotor disturbance or depressed mood?].
AB  - Melancholia is a historical concept according to which the clinical condition is
      characterised by gloom, apprehension and psychomotor disturbance, vital symptoms
      and psychotic phenomena. The condition needs to be accurately diagnosed if
      treatment is to be appropriate. If a patient shows no clear signs of depression,
      psychomotor disturbance is often not recognised as a feature of severe depression
      and as a result treatment is delayed. On the basis of two case studies we show
      that psychomotor symptoms can be extremely important for an accurate clinical
      evaluation.

PMID- 20697999
TI  - [Eye movement desensitisation and reprocessing (EMDR) as a treatment for phantom
      limb pain].
AB  - A 68-year-old man, who had had phantom limb pain in his leg and foot for 27
      years, was referred for EMDR treatment. This case study shows that after 10
      sessions of EMDR the pain intensity had diminished from 10 to 1 (on a scale of
      10). Further sessions, consisting mainly of discussions, focused on consolidation
      of the result, namely on finding a new physical and mental balance and on
      strengthening self-confidence in the new situation.

PMID- 20698000
TI  - [Reaction on 'A psychodynamic approach to self-harm in patients with a borderline
      personality disorder'].

PMID- 20698001
TI  - [Reaction on 'Follow-up of the MTAstudy in children with ADHD: what do the data
      tell us, and what not?'].

PMID- 20698002
TI  - [Reaction on 'Antipsychotics and metabolic abnormalities in children and
      adolescents; a review of the literature and some recommendations'].

PMID- 20698004
TI  - A retrospective analysis of sphenoid sinus hypoplasia and agenesis using dental
      volumetric CT in Turkish individuals.
AB  - PURPOSE: In adults, sphenoid sinus agenesis is an extremely rare anomaly. The
      objective of this study was to investigate the prevalence of sphenoid sinus
      hypoplasia and agenesis using dental volumetric computed tomography (DVCT) in a
      population of Turkish individuals. MATERIALS AND METHODS: DVCT scans in the
      axial, coronal and sagittal planes of the sphenoid sinus of 384 patients were
      examined for evidence of sphenoid sinus agenesis and hypoplasia. RESULTS: In the
      DVCT scans, bilateral agenesis of sphenoid sinus was not seen. Unilateral
      agenesis of sphenoid sinus was seen in 0.26% of the sample, and sphenoid sinus
      hypoplasia was seen in 0.52%. Unilateral hypoplasia of the sphenoid sinus was
      observed in 0.26% of the sample, and bilateral hypoplasia of sphenoid sinus was
      observed in 0.26%. CONCLUSION: In this study, we found a low frequency of
      sphenoid sinus agenesis. Compared with sphenoid sinus agenesis, the frequency of
      sphenoid sinus hypoplasia was higher. DVCT may be used as a diagnostic tool to
      investigate the paranasal sinus.

PMID- 20698003
TI  - Can renal dimensions and the main renal artery diameter indicate the presence of
      an accessory renal artery? A 64-slice CT study.
AB  - PURPOSE: To evaluate whether renal dimensions and the main renal artery (mRA)
      diameter can provide indirect evidence of the presence or absence of accessory
      renal arteries (aRA). MATERIALS AND METHODS: The study group consisted of 167
      patients (83 women, 84 men; mean age, 52.4+/-13.1 years) who presented to our
      radiology department for abdominal CT examinations with various indications. CT
      examination was performed on a 64-slice CT scanner in the arterial phase. The
      kidney diameters were recorded. The number of renal arteries supplying each
      kidney was evaluated, and their diameters were measured. We attempted to
      determine a formula that could be used to predict the presence or absence of
      aRAs. RESULTS: One or multiple aRAs were found in 76 (22.8%) of the 334 kidneys.
      The mRA diameter was 5.51+/-0.96 mm. The mRA diameter was smaller in kidneys with
      aRAs than in those without (P < 0.001). A cut-off value of 4.15 mm for the
      diameter of mRA to predict the presence of aRAs led to negative and positive
      predictive values of 80% and 90%, respectively. A formula that can predict that
      an aRA is absent with 97% accuracy given the values of the mRA diameter and the
      kidney length was determined using logistic regression. CONCLUSION: The mRA
      diameter (4.15 mm) alone and the results of the formula developed herein
      employing the mRA diameter and kidney length can respectively predict the
      presence or absence of an aRA with high accuracy.

PMID- 20698005
TI  - Carotid CT angiography: comparison of image quality for left versus right arm
      injections.
AB  - PURPOSE: To evaluate the differences in image quality of carotid computed
      tomographic angiography (CTA) of patients injected with contrast material in
      their right arms versus patients injected with contrast material in their left
      arms. MATERIALS AND METHODS: Patients who had cerebrovascular accidents and
      subsequently underwent CTA were included in the study. Contrast material was
      injected into the right arms of 44 patients and into the left arms of 46
      patients. Source images of a total of 90 CTAs were retrospectively evaluated for
      perivenous streak artifacts and contrast material reflux into the veins of the
      neck and upper thorax. After adjusting for differences in gender, the
      relationship between the injection site and the intensity of perivenous streak
      artifacts and venous reflux was determined. RESULTS: Perivenous streak artifacts
      and venous reflux were demonstrated in patients who underwent either right or
      left arm injections. However, the intensity of perivenous streak artifacts was
      stronger in patients who were injected with contrast material in the left arm.
      Venous reflux into the neck and upper thorax veins was also more severe and more
      frequent with left arm injections. A decreased retrosternal distance facilitated
      reversed flow into the veins when the left arm injection was used. CONCLUSION:
      Perivenous beam hardening streak artifacts and venous reflux could not be
      prevented with right or left arm injections. However, patients who were injected
      with contrast material in their right arms showed fewer artifacts, thus allowing
      for better quality images on CTA.

PMID- 20698006
TI  - Triple metallic stenting in hilar malignant biliary obstructions.
AB  - PURPOSE: To research the effects of triple stenting on primary patency rates and
      on clinical and biochemical findings in patients with high-level malignant
      biliary obstruction. MATERIALS AND METHODS: We analyzed eight patients who had
      undergone triple stenting for hilar malignant biliary obstruction, mainly with
      the percutaneous approach, between January 2009, and September 2009. Pre
      interventional bilirubin levels and the existence of pruritus or cholangitis were
      recorded. Patients were examined 15 days and three months post-intervention.
      Procedure-related mortality and 30-day mortality rates were recorded. Changes in
      the serum bilirubin levels, pruritis and cholangitis were examined. Primary
      patency rates were calculated with the Kaplan-Meier method. RESULTS: Pruritis and
      cholangitis improved within 15 days. There was a significant decrease in serum
      bilirubin levels, which were very near to normal limits. Two patients died: one
      in the fourth month and the other in the eighth month. The mean patency rate was
      179+/-18.81 days. There were no procedure-related or 30-day mortalities in the
      study group. CONCLUSION: Triple metallic stenting did not significantly improve
      primary patency rates in hilar malignant biliary obstructions. However, the
      beneficial effects of triple stenting included the rapid improvement in clinical
      and biochemical signs in select patients. Triple stenting will be beneficial in
      preventing isolation that might cause cholangitis. Malignant biliary obstruction
      in patients with a trifurcation anomaly in the hilar region may necessitate
      triple stenting.

PMID- 20698007
TI  - Percutaneous management of malignant biliary disease: factors influencing the
      ability to overcome the stricture.
AB  - PURPOSE: To determine the factors affecting the ability to cross malignant
      biliary obstructions in percutaneous transhepatic interventions. MATERIALS AND
      METHODS: In this study, 256 patients with 310 obstructive malignant biliary
      lesions from May 2006 to January 2009 were analyzed retrospectively. All of the
      patients had undergone percutaneous transhepatic cholangiography and
      intervention. Obstructions crossed in two or fewer sessions were classified as
      technically easy obstructions, whereas obstructions that required more than two
      sessions for crossing were classified as technically difficult obstructions.
      Possible factors thought to affect the ability of malignant biliary obstructions
      to be crossed were compared according to the obstruction type (technically easy
      or difficult obstructions). RESULTS: Of the 310 malignant biliary obstructions
      studied, 79% (246) were technically easy to cross, and 21% (64) were technically
      difficult to cross. Lesions located between the hilum and the cystic duct and
      beak-shaped malignant biliary lesions were easily crossed, but suprahilar
      localized lesions and flat or ovoid-shaped lesions were difficult to cross. The
      histological nature of the malignant biliary obstruction, the direct-to-total
      bilirubin ratio, the entry segment for the intervention, the largest bile duct
      diameter proximal to the obstruction, and the length of the obstruction were not
      found to influence the ability of the stricture to be overcome. CONCLUSION: In
      patients with malignant biliary obstructions, the factors that can negatively
      affect obstruction crossing are lesions with suprahilar localization and flat or
      ovoid-shaped lesions. We also conclude that after five ineffective attempts have
      been made to pass the stricture, treatment of malignant biliary obstruction
      should proceed to external biliary drainage.

PMID- 20698008
TI  - Is quantitative diffusion-weighted MRI a reliable method in the assessment of the
      inflammatory activity in ulcerative colitis?
AB  - PURPOSE: We investigated the relationship between the apparent diffusion
      coefficient (ADC) values of the colonic wall and the pathologic pericolonic lymph
      nodes (PCLNs) and inflammatory activity in ulcerative colitis patients by
      diffusion-weighted magnetic resonance imaging (DW-MRI). MATERIALS AND METHODS: A
      total of 28 ulcerative colitis patients (9 endoscopically active, 10 subacute and
      9 in remission) were evaluated by DW-MRI with 0, 500 and 1000 s/mm2 b-values. The
      ADC values of the rectum and sigmoid colon walls and the adjacent PCLNs were
      obtained for quantitative analysis. The DW-MRI findings were compared to the
      disease activity. RESULTS: The ADC values of the sigmoid colon were similar in
      patients with active, subacute and remissive ulcerative colitis (P = 0.472). The
      ADC values of the rectum were different (P = 0.009) between patients in the
      active (1.08 +/- 0.14*10-3 mm2/s) and subacute phases (1.13 +/- 0.23*10-3 mm2/s)
      of disease and those in remission (1.29 +/- 0.17*10-3 mm2/s). The ADC values of
      the PCLNs (P = 0.899) did not differ with respect to disease activity.
      CONCLUSION: DW-MRI is useful in identifying disease activity in ulcerative
      colitis patients, especially with respect to the rectum. The ADC values of the
      rectum increase during remission and decrease in patients with active distal
      colitis. The ADC values of the PCLNs were not useful in determining disease
      activity.

PMID- 20698010
TI  - The vitamin D revolution.

PMID- 20698011
TI  - Prion protein in Alzheimer's pathogenesis: a hot and controversial issue.
AB  - The role for cellular prion protein PrP(c) in beta-amyloid (Abeta) oligomer
      induced synaptic impairment is a topic of great interest and some controversy. In
      this issue of EMBO Molecular Medicine Aguzzi and co-workers explore the
      contribution of PrP(c) to deficient long term potentiation (LTP) and soluble
      Abeta levels in an Alzheimer's disease mouse model and show that the role of
      prions in Abeta related toxicity is far from 'black and white' suggesting complex
      interpretations of the data available thus far.

PMID- 20698012
TI  - Advancing children's rights to be heard and protected: The model representation
      of children in abuse, neglect, and custody proceedings act.
AB  - Litigation surrounding family matters can have a significant impact on children
      well into their adult years. Because their interests may differ from those of
      their parents or other caretakers, it is crucial that the legal system provide a
      mechanism to ensure that children's interests are both protected by and
      appropriately communicated to the family court. The legal community has not
      reached a consensus regarding how children's interests can best be protected--or
      the appropriate role for attorneys involved in such cases. In fact, a number of
      professional organizations have proposed standards that impose differing
      obligations upon attorneys. In this article, the strengths and limitations of
      various practice standards are compared and contrasted, with the focus being on
      how children's interests can best communicated to, and protected by, the court.

PMID- 20698013
TI  - Isolation and characterization of lactic acid bacteria from jiang-sun (fermented
      bamboo shoots), a traditional fermented food in Taiwan.
AB  - BACKGROUND: In this study, lactic acid bacteria (LAB) were isolated,
      characterized and identified from jiang-sun (fermented bamboo shoots; a
      traditional fermented food in Taiwan). Samples were collected at seven time
      intervals from a fixed fermenting bucket during the fermentation process of jiang
      sun and its initial ingredients, dochi (fermented soybeans) and bamboo shoots.
      RESULTS: A total of 57 LAB cultures were isolated; 42 cultures were isolated from
      jiang-sun samples and 15 cultures were isolated from dochi and bamboo shoots.
      These isolates were characterized phenotypically and then divided into three
      groups (A-C) by restriction fragment length polymorphism analysis and sequencing
      of 16S ribosomal DNA. Alteration of microbial populations during the fermentation
      process was observed. While various LAB were found in the dochi and bamboo
      shoots, it was mostly replaced by Lactobacillus plantarum after 1 day of
      fermentation. Furthermore, the antibacterial activities of the isolates were
      determined, and one Enterococcus faecium strain showed inhibitory activity
      against all the indicator strains. CONCLUSION: Results suggest that L. plantarum
      is the main LAB present during the fermentation of jiang-sun. To our knowledge,
      this is the first report describing the distribution and varieties of LAB that
      exist in the jiang-sun fermentation process.

PMID- 20698019
TI  - Management practices and risk of occupational blood exposure in U.S. paramedics:
      Needlesticks.
AB  - BACKGROUND: The purpose of this study was to present risk estimates for
      needlestick in U.S. paramedics and estimated risk ratios for selected management
      practices. METHODS: A mail survey was conducted among a national sample of U.S.
      paramedics in 2002-2003. RESULTS: The adjusted response rate was 55% (n = 2,664).
      The overall 12-month risk of needlestick was 6.7% (95% confidence interval, 5.4
      7.9). Risk ratios for provision of safety-engineered medical devices and two
      supervisory behaviors that emphasized safe work practices ranged from 2.5 to 3.2.
      The protective effect of working in an environment that included both of the
      supervisory behaviors was greater than the protective effect of always being
      provided with safety devices. A sensitivity analysis indicated that the risk
      ratio estimates were unlikely to be inflated by nonresponse bias. CONCLUSIONS:
      These results suggest that greater provision of safety devices and interventions
      aimed at management practices that promote worker safety could substantially
      reduce the risk of needlestick among U.S. paramedics.

PMID- 20698020
TI  - Are immigrants, ethnic and linguistic minorities over-represented in jobs with a
      high level of compensated risk? Results from a Montreal, Canada study using
      census and workers' compensation data.
AB  - OBJECTIVES: Few Canadian data sources allow the examination of disparities by
      ethnicity, language, or immigrant status in occupational exposures or health
      outcomes. However, it is possible to document the mechanisms that can create
      disparities, such as the over-representation of population groups in high-risk
      jobs. We evaluated, in the Montreal context, the relationship between the social
      composition of jobs and their associated risk level. METHODS: We used data from
      the 2001 Statistics Canada census and from Quebec's workers' compensation board
      for 2000-2002 to characterize job categories defined as major industrial groups
      crossed with three professional categories (manual, mixed, non-manual).
      Immigrant, visible, and linguistic minority status variables were used to
      describe job composition. The frequency rate of compensated health problems and
      the average duration of compensation determined job risk level. The relationship
      between the social composition and risk level of jobs was evaluated with Kendall
      correlations. RESULTS: The proportion of immigrants and minorities was positively
      and significantly linked to the risk level across job categories. Many
      relationships were significant for women only. In analyses done within manual
      jobs, relationships with the frequency rate reversed and were significant, except
      for the relationship with the proportion of individuals with knowledge of French
      only, which remained positive. CONCLUSIONS: Immigrants, visible, and linguistic
      minorities in Montreal are more likely to work where there is an increased level
      of compensated risk. Reversed relationships within manual jobs may be explained
      by under-reporting and under-compensation in vulnerable populations compared to
      those with knowledge of the province's majority language.

PMID- 20698021
TI  - Factors associated with safe patient handling behaviors among critical care
      nurses.
AB  - BACKGROUND: Patient handling is a major risk factor for musculoskeletal (MS)
      injury among nurses. The aims of the study were to describe nurses' work
      behaviors related to safe patient handling and identify factors influencing their
      safe work behaviors, including the use of lifting equipment. METHODS: A cross
      sectional study using a mailed questionnaire with a nationwide random sample of
      361 critical care nurses. Nurses reported on the physical, psychosocial, and
      organizational characteristics of their jobs and on their MS symptoms, risk
      perception, work behaviors, and demographics. Hierarchical multiple linear
      regression analyses were used to identify significant factors. RESULTS: More than
      half of participants had no lifting equipment on their unit, and 74% reported
      that they performed all patient lift or transfer tasks manually. Significant
      factors for safer work behavior included better safety climate, higher effort
      reward imbalance, less overcommitment, greater social support, and day shift
      work. Physical workload, personal risk perception, or MS symptom experiences were
      not associated with safe work behavior. CONCLUSIONS: Safe work behaviors are best
      understood as socio-cultural phenomena influenced by organizational,
      psychosocial, and job factors but, counter to extant theories of health
      behaviors, do not appear to be related to personal risk perception. Management
      efforts to improve working conditions and enhance safety culture in hospitals
      could prove to be crucial in promoting nurses' safe work behavior and reducing
      risk of MS injury.

PMID- 20698022
TI  - Use of O*NET as a job exposure matrix: A literature review.
AB  - BACKGROUND: O*NET is a publicly available online database that describes
      occupational features across US job titles and that has been used to estimate
      workplace physical and psychosocial exposures and organizational characteristics.
      The aim of this review is to describe and evaluate the use of O*NET as a job
      exposure matrix. METHODS: A review of the peer-reviewed published and gray
      literature was conducted. Twenty-eight studies were found that used O*NET to
      estimate work exposures related to health or safety outcomes. Each was
      systematically evaluated across eight main features. RESULTS: Many health
      outcomes have been studied with O*NET estimates of job exposures. Some studies
      did not use conceptual definitions of exposure; few studies estimated convergent
      validity, most used predictive validity. Multilevel analysis was underutilized.
      CONCLUSION: O*NET is worthy of exploration by the occupational health community,
      although its scientific value is still undetermined. More studies could
      eventually provide evidence of convergent validity. O*NET has the potential to
      allow examination of occupational risks that might have otherwise been ignored
      due to missing data or resource constraints on field data collection of job
      exposure information.

PMID- 20698023
TI  - Neuromotor effects of short-term and long-term exposures to trichloroethylene in
      workers.
AB  - BACKGROUND: Health effects of long-term exposure to organic solvents at low
      levels are a major concern in industrialized countries. To assess the neuromotor
      impact of trichloroethylene objectively, static postural sway and hand tremor
      parameters, along with urinary trichloroethanol (TCOH) and trichloroacetic acid
      (TCAA) levels, were investigated in 57 workers without obvious neurological
      disorders and 60 control subjects. METHODS: The workers had been occupationally
      exposed to trichloroethylene for 0.1-37 years. The cumulative exposure index
      (CEI) was calculated from their occupational history and total trichloro
      compounds (TCOH + TCAA). RESULTS: Median levels in the workers were 1.7 mg/L for
      TCOH and 2.5 mg/L for TCAA, and the maximum ambient trichloroethylene
      concentration was estimated to be <22 ppm from the previously reported equation
      using TCOH + TCAA. Sway parameters with eyes open and tremor intensity in
      dominant hand were significantly larger in the exposed workers than in the
      control subjects when adjusting for possible confounders. A significant dose
      effect association was seen between two sway parameters and urinary TCOH level in
      the workers. Tremor intensities in non-dominant hand differed significantly among
      three groups of the workers divided according to the CEI. CONCLUSIONS: These
      findings suggest that trichloroethylene exposure, even at low levels of less than
      the short-term exposure limit by the ACGIH, can affect the neuromotor function of
      workers. The postural instability appears to result from recent exposure, and the
      increased tremor may occur due to short-term and long-term exposures. Hereafter,
      such objective measures, along with subjective symptoms, should be carefully used
      for the occupational exposure limit setting.

PMID- 20698024
TI  - Risk factors for worker injury and death from occupational light vehicles crashes
      in New South Wales (Australia).
AB  - BACKGROUND/AIM: To identify risk and protective factors for crash casualty
      outcomes in occupational light vehicles (OLV), a previously under-recognized work
      context for injuries and fatalities. METHODS: A register-based study was
      conducted using linked vehicle crash and registration data (n = 13,491) for the
      Australian state of New South Wales. Univariate and multivariate analyses were
      undertaken to assess the relationship between casualty outcomes and variables
      drawn from four domains of potential determinants of severity: user, vehicle,
      road, and work organization factors. RESULTS: Nineteen percent of OLV crashes had
      OLV-user casualties (n = 2,506) and 1% fatalities (n = 34). Adjusted casualty
      risk factors included tired driver (OR 2.1, 95% CI 1.5-2.7), no seat belt use (OR
      1.8, 95% CI 1.4-2.3), and excessive speed (OR 1.4, 95% CI 1.2-1.6). Adjusted
      fatality risk factors were no seat belt (OR 12.9, 95% CI 4.9-34.3) and high-speed
      zone crash (OR 5.0, 95% CI 2.1-12.3). CONCLUSIONS: OLV users are at risk from
      both recognized road risks and hazards specific to OLV use. Findings suggest that
      risk reduction could be improved by the use of safer vehicles, fatigue
      management, and journey planning.

PMID- 20698025
TI  - Sex differences in cerebral ischemia: possible molecular mechanisms.
AB  - Sex is emerging as an important factor in the etiology and expression of many
      different pathological conditions, including stroke. Initially, the levels of sex
      hormones were thought to be the major contributor to these sex differences,
      especially after puberty, when gonadal steroid levels sharply diverge between the
      sexes. More recently, it is recognized that sex differences also result from the
      organizational effects of sex hormone exposure early in development, even in the
      absence of hormone exposure later in life, as well as effects mediated by the sex
      chromosomes themselves. Epigenetic modifications of developmental genes important
      in sexual differentiation and the response to sex steroid hormones are also
      emerging as another important contributor to sex differences in disease
      expression. This review describes recent research on the relationship between
      hormones, organizational-activational effects of gonadal steroids, and epigenetic
      modifications in brain pathology, focusing specifically on cerebral ischemia.

PMID- 20698026
TI  - Better care with a personal touch.

PMID- 20698027
TI  - MicroRNAs revolutionizing cancer knowledge and treatment.

PMID- 20698028
TI  - Relational aggression in marriage.
AB  - Drawing from developmental theories of relational aggression, this article
      reports on a study designed to identify if spouses use relationally aggressive
      tactics when dealing with conflict in their marriage and the association of these
      behaviors with marital outcomes. Using a sample of 336 married couples (672
      spouses), results revealed that the majority of couples reported that
      relationally aggressive behaviors, such as social sabotage and love withdrawal,
      were a part of their marital dynamics, at least to some degree. Gender
      comparisons of partner reports of their spouse's behavior revealed that wives
      were significantly more likely to be relationally aggressive than husbands.
      Structural equation modeling demonstrated that relational aggression is
      associated with lower levels of marital quality and greater marital instability
      for both husbands and wives. Implications are drawn for the use of relational
      aggression theory in the future study of couple conflict and marital aggression.

PMID- 20698029
TI  - Radiosynthesis of the candidate beta-amyloid radioligand [(11)C]AZD2184: Positron
      emission tomography examination and metabolite analysis in cynomolgus monkeys.
AB  - Beta-amyloid accumulation is associated with the pathogenesis of Alzheimer's
      disease (AD). AZD2184, a new radioligand for high-contrast positron emission
      tomography (PET) imaging of Abeta-deposits, has recently been developed and
      characterized in vitro and in rodents ex vivo. The objective of this study was to
      label AZD2184 with carbon-11, to perform in vivo characterization of
      [(11)C]AZD2184 ([(11)C]5) in the cynomolgus monkey brain as well as whole-body
      dosimetry, and to examine the metabolism of the labeled radioligand. [(11)C]5 was
      prepared by a two-step radiosynthesis starting with the reaction of 5-(6-(tert
      butyldimethylsilyloxy)benzo[d]thiazol-2-yl)pyridin-2-amine with [(11)C]methyl
      iodide followed by deprotection using water. Four brain PET measurements in two
      cynomolgus monkeys and one whole-body PET measurement were performed with
      [(11)C]5. There was a high and rapid brain uptake (2.2-3.4% of injected dose at 2
      min). The distribution of brain radioactivity was fairly uniform, with early to
      late-brain concentration ratios (peak vs. 60 min) higher for [(11)C]5 than ratios
      previously reported for [(11)C]PIB (8.2 and 4.6, respectively). Based on the
      whole-body data, it was estimated that an effective dose in an adult male would
      be 6.2 muSv/MBq and thus would be safe from a radiation point of view for
      multiple scans within the same year. [(11)C]5 shows binding characteristics,
      suggesting low levels of white-matter retention, and may thus provide improved
      contrast when compared with currently used PET radioligands for visualization of
      Abeta-deposits. On the basis of the labeling chemistry and the results of the
      biological evaluation, we conclude that [(11)C]5 should be useful for routine
      clinical studies.

PMID- 20698030
TI  - Different chronic cocaine administration protocols induce changes on dentate
      gyrus plasticity and hippocampal dependent behavior.
AB  - Hippocampus is a limbic structure that participates in learning and memory
      formation. Specifically the dentate gyrus has been described as a hippocampal
      subregion with high rates of plasticity and it is targeted by different
      psychoactive drugs modulating synaptic plasticity. Repeated cocaine
      administration induces sensitization to the locomotor effects and it is believed
      that sensitization involves the same mechanisms of drug seeking and relapse.
      Although, the mechanisms underlying sensitization is not fully understood. In
      this work we investigated the impact of repeated intraperitoneal administration
      of cocaine (15 or 20 mg/kg/day along 5 or 15 days respectively; and 15 mg/kg/day
      along 5 day followed by a challenge dose after three days of withdrawal) on the
      dentate gyrus synaptic plasticity, differentiating between sensitized and
      nonsensitized rats. Furthermore, we correlated changes on the hippocampal
      synaptic plasticity to memory retention. Our results revealed that the prevalence
      of cocaine sensitization (around 50%) was identical in all protocols used. The
      results found in the threshold to generate LTP were similar for all protocols
      used, being the threshold values cocaine-treated groups (sensitized and
      nonsensitized) significantly reduced compared to controls, observing the highest
      reduction in the sensitized group. Moreover, we observed a facilitated retention
      of recent memory formation only in sensitized animals the nonsensitized subjects
      remained at the control levels. In conclusion, sensitization to cocaine generates
      a high efficiency of hippocampal synaptic plasticity that may underlie the
      aberrant engagement of learning processes occurred during drug addiction.

PMID- 20698031
TI  - Neurites from PC12 cells are connected to each other by synapse-like structures.
AB  - PC12 cells have been used as a model of sympathetic neurons. Nerve growth factor
      (NGF), basic fibroblast growth factor (bFGF), and cAMP induce neurite outgrowth
      from PC12 cells. cAMP induced a greater number of neurites than did NGF. In
      particular, we attempted to elucidate whether PC12 cell neurites, induced by
      several factors including NGF, bFGF, and cAMP, form synapses, and whether each
      neurite has presynaptic and postsynaptic properties. Using scanning electron
      microscopy (SEM) and transmission electron microscopy (TEM), we observed that
      neurites are connected to each other. The connected regions presented dense core
      vesicles and a clathrin-coated membrane invagination. In addition, typical maker
      proteins for axon and dendrite were identified by an immuno-staining method. Tau
      1, an axonal marker in neurons, was localized at a high concentration in the
      terminal tips of neurites from PC12 cells, which were connected to neurite
      processes containing MAP-2, a dendritic marker in neurons. Furthermore, neurites
      containing SV2 and synaptotagmin, markers of synaptic vesicles, were in contact
      with neurites harboring drebrin, a marker of the postsynaptic membrane,
      suggesting that neurites from PC12 cells induced by NGF, bFGF, and cAMP may form
      synapse-like structures. Tat-C3 toxin, a Rho inhibitor, augmented neurite
      outgrowth induced by NGF, bFGF, and cAMP. Tat-C3 toxin together with
      neurotrophins also exhibited synapse-like structures between neurites. However,
      it remains to be studied whether RhoA inhibition plays a role in the formation of
      synapse-like structures in PC12 cells.

PMID- 20698032
TI  - (+)-Methamphetamine-induced monoamine reductions and impaired egocentric learning
      in adrenalectomized rats is independent of hyperthermia.
AB  - Methamphetamine (MA) is widely abused and implicated in residual cognitive
      deficits. In rats, increases in plasma corticosterone and egocentric learning
      deficits are observed after a 1-day binge regimen of MA (10 mg/kg x 4 at 2-h
      intervals). The purpose of this experiment was to determine if adrenal
      inactivation during and following MA exposure would attenuate the egocentric
      learning deficits in the Cincinnati water maze (CWM). In the first experiment,
      the effects of adrenalectomy (ADX) or sham surgery (SHAM) on MA-induced
      neurotoxicity at 72 h were determined. SHAM-MA animals showed typical patterns of
      hyperthermia, whereas ADX-MA animals were normothermic. Both SHAM-MA- and ADX-MA
      treated animals showed increased neostriatal glial fibrillary acidic protein and
      decreased monoamines in the neostriatum, hippocampus, and entorhinal cortex. In
      the second experiment, SHAM-MA- and ADX-MA-treated groups showed equivalently
      impaired CWM performance 2 weeks post-treatment (increased latencies, errors, and
      start returns) compared to SHAM-saline (SAL) and ADX-SAL groups with no effects
      on novel object recognition, elevated zero maze, or acoustic startle/prepulse
      inhibition. Post-testing, monoamine levels remained decreased in both MA-treated
      groups in all three brain regions, but were not as large as those observed at 72
      h post-treatment. The data demonstrate that MA-induced learning deficits can be
      dissociated from drug-induced increases in plasma corticosterone or hyperthermia,
      but co-occur with dopamine and serotonin reductions.

PMID- 20698034
TI  - Gastroesophageal reflux disease: From heartburn to cancer.
AB  - About 10%-15% of patients with gastroesophageal reflux disease develop Barrett's
      esophagus. This is considered a premalignant condition because it can progress
      from metaplasia to high-grade dysplasia, and eventually to adenocarcinoma.
      Recently, major advances have been made in the endoscopic treatment of Barrett's
      esophagus, therefore limiting the role of surgery in the treatment of this
      disease.

PMID- 20698033
TI  - AMPK-associated signaling to bridge the gap between fuel metabolism and
      hepatocyte viability.
AB  - The adenosine monophosphate-activated protein kinase (AMPK) and p70 ribosomal S6
      kinase-1 pathway may serve as a key signaling flow that regulates energy
      metabolism; thus, this pathway becomes an attractive target for the treatment of
      liver diseases that result from metabolic derangements. In addition, AMPK emerges
      as a kinase that controls the redox-state and mitochondrial function, whose
      activity may be modulated by antioxidants. A close link exists between fuel
      metabolism and mitochondrial biogenesis. The relationship between fuel metabolism
      and cell survival strongly implies the existence of a shared signaling network,
      by which hepatocytes respond to challenges of external stimuli. The AMPK pathway
      may belong to this network. A series of drugs and therapeutic candidates enable
      hepatocytes to protect mitochondria from radical stress and increase cell
      viability, which may be associated with the activation of AMPK, liver kinase B1,
      and other molecules or components. Consequently, the components downstream of
      AMPK may contribute to stabilizing mitochondrial membrane potential for
      hepatocyte survival. In this review, we discuss the role of the AMPK pathway in
      hepatic energy metabolism and hepatocyte viability. This information may help
      identify ways to prevent and/or treat hepatic diseases caused by the metabolic
      syndrome. Moreover, clinical drugs and experimental therapeutic candidates that
      directly or indirectly modulate the AMPK pathway in distinct manners are
      discussed here with particular emphasis on their effects on fuel metabolism and
      mitochondrial function.

PMID- 20698035
TI  - Gastroesophageal reflux disease: From pathophysiology to treatment.
AB  - This review focuses on the pathophysiology of gastroesophageal reflux disease
      (GERD) and its implications for treatment. The role of the natural anti-reflux
      mechanism (lower esophageal sphincter, esophageal peristalsis, diaphragm, and
      trans-diaphragmatic pressure gradient), mucosal damage, type of refluxate,
      presence and size of hiatal hernia, Helicobacter pylori infection, and Barrett's
      esophagus are reviewed. The conclusions drawn from this review are: (1) the
      pathophysiology of GERD is multifactorial; (2) because of the pathophysiology of
      the disease, surgical therapy for GERD is the most appropriate treatment; and (3)
      the genesis of esophageal adenocarcinoma is associated with GERD.

PMID- 20698036
TI  - Advances in diagnostic testing for gastroesophageal reflux disease.
AB  - Gastroesophageal reflux disease (GERD) contributes substantially to morbidity and
      to costs in the United States health care system. The burden of this disease has
      resulted in attempts at improving diagnosis and characterizing patients. Numerous
      research and technical advances have enhanced our understanding of both the
      utility and limitations of a variety of diagnostic modalities. The purpose of
      this review is to highlight recent advances in GERD diagnostic testing and to
      discuss their implications for use in clinical practice. Topics addressed include
      esophageal pH monitoring, impedance testing, symptom association analyses, narrow
      band imaging, and histopathology.

PMID- 20698037
TI  - Gastroesophageal reflux disease and severe obesity: Fundoplication or bariatric
      surgery?
AB  - Increases in the prevalence of obesity and gastroesophageal reflux disease (GERD)
      have paralleled one another over the past decade, which suggests the possibility
      of a linkage between these two processes. In both instances, surgical therapy is
      recognized as the most effective treatment for severe, refractory disease.
      Current surgical therapies for severe obesity include (in descending frequency)
      Roux-en-Y gastric bypass, adjustable gastric banding, sleeve gastrectomy, and
      biliopancreatic diversion with duodenal switch, while fundoplication remains the
      mainstay for the treatment of severe GERD. In several large series, however, the
      outcomes and durability of fundoplication in the setting of severe obesity are
      not as good as those in patients who are not severely obese. As such, bariatric
      surgery has been suggested as a potential alternative treatment for these
      patients. This article reviews current concepts in the putative
      pathophysiological mechanisms by which obesity contributes to gastroesophageal
      reflux and their implications with regards to surgical therapy for GERD in the
      setting of severe obesity.

PMID- 20698039
TI  - Effect of medical and surgical treatment of Barrett's metaplasia.
AB  - Barrett's esophagus (BE) is a change in the esophageal mucosa as a result of long
      standing gastroesophageal reflux disease. The importance of BE is that it is the
      main risk factor for the development of esophageal adenocarcinoma, whose
      incidence is currently growing faster than any other cancer in the Western world.
      The aim of this review was to compare the common treatment modalities of BE, with
      the focus on proton pump inhibitors and operative fundoplication. We performed a
      literature search on medical and surgical treatment of BE to determine eligible
      studies for this review. Studies on medical and surgical treatment of BE are
      discussed with regard to treatment effect on progression and regression of
      disease. Although there is some evidence for control of reflux with either
      medical or surgical therapy, there is no definitive evidence that either
      treatment modality decreases the risk of progression to dysplasia or cancer. Even
      though there is a trend toward antireflux surgery being superior, there are no
      definitive studies to prove this.

PMID- 20698038
TI  - Pathophysiology and treatment of Barrett's esophagus.
AB  - Gastroesophageal reflux disease (GERD) affects an estimated 20% of the population
      in the United States. About 10%-15% of patients with GERD develop Barrett's
      esophagus, which can progress to adenocarcinoma, currently the most prevalent
      type of esophageal cancer. The esophagus is normally lined by squamous mucosa,
      therefore, it is clear that for adenocarcinoma to develop, there must be a
      sequence of events that result in transformation of the normal squamous mucosa
      into columnar epithelium. This sequence begins with gastroesophageal reflux, and
      with continued injury metaplastic columnar epithelium develops. This article
      reviews the pathophysiology of Barrett's esophagus and implications for its
      treatment. The effect of medical and surgical therapy of Barrett's esophagus is
      compared.

PMID- 20698040
TI  - Endoscopic treatment of Barrett's esophagus: From metaplasia to intramucosal
      carcinoma.
AB  - The annual incidence of adenocarcinoma arising from Barrett's esophagus (BE) is
      approximately 0.5%. Through a process of gradual transformation from low-grade
      dysplasia to high-grade dysplasia (HGD), adenocarcinoma can develop in the
      setting of BE. The clinical importance of appropriate identification and
      treatment of BE in its various stages, from intestinal metaplasia to intramucosal
      carcinoma (IMC) hinges on the dramatically different prognostic status between
      early neoplasia and more advanced stages. Once a patient has symptoms of
      adenocarcinoma, there is usually locally advanced disease with an approximate 5
      year survival rate of about 20%. Esophagectomy has been the gold standard
      treatment for BE with HGD, due to the suspected risk of harboring occult invasive
      carcinoma, which was traditionally estimated to be as high as 40%. In recent
      years, the paradigm of BE early neoplasia management has recently evolved, and
      endoscopic therapies (endoscopic mucosal resection, radiofrequency ablation, and
      cryotherapy) have entered the clinical forefront as acceptable non-surgical
      alternatives for HGD and IMC. The goal of endoscopic therapy for HGD or IMC is to
      ablate all BE epithelium (both dysplastic and non-dysplastic) due to risk of
      synchronous/metachronous lesion development in the remaining BE segment.

PMID- 20698041
TI  - Esophageal resection for high-grade dysplasia and intramucosal carcinoma: When
      and how?
AB  - High-grade dysplasia (HGD) and intramucosal carcinoma (IMC) in the setting of
      Barrett's esophagus have traditionally been treated with esophagectomy. However,
      with the advent of endoscopic mucosal resection and endoscopic ablative
      therapies, endoscopic therapy at centers with expertise is now an established
      treatment of Barrett's-esophagus-related neoplasia, including HGD and IMC.
      Esophagectomy is today reserved for more selected cases with submucosal invasion,
      evidence for lymph node metastasis, or unsuccessful endoscopic therapy.

PMID- 20698043
TI  - Transhiatal versus transthoracic esophagectomy for esophageal cancer.
AB  - Esophageal cancer continues to represent a formidable challenge for both patients
      and clinicians. Relative 5-year survival rates for patients have improved over
      the past three decades, probably linked to a combination of improved surgical
      outcomes, progress in systemic chemotherapy and radiotherapy, and the increasing
      acceptance of multimodality treatment. Surgical treatment remains a fundamental
      component of the treatment of localized esophageal adenocarcinoma. Multiple
      approaches have been described for esophagectomy, which can be thematically
      grouped under two major categories: either transthoracic or transhiatal. The main
      controversy rests on whether a more extended resection through thoracotomy
      provides superior oncological outcomes as opposed to resection with relatively
      limited morbidity and mortality through a transhiatal approach. After numerous
      trials have addressed these issues, neither approach has consistently proven to
      be superior to the other one, and both can provide excellent short-term results
      in the hands of experienced surgeons. Moreover, the available literature suggests
      that experience of the surgeon and hospital in the surgical management of
      esophageal cancer is an important factor for operative morbidity and mortality
      rates, which could supersede the type of approach selected. Oncological outcomes
      appear to be similar after both procedures.

PMID- 20698044
TI  - Minimally invasive esophagectomy.
AB  - Esophageal resection is associated with a high morbidity and mortality rate.
      Minimally invasive esophagectomy (MIE) might theoretically decrease this rate. We
      reviewed the current literature on MIE, with a focus on the available techniques,
      outcomes and comparison with open surgery. This review shows that the available
      literature on MIE is still crowded with heterogeneous studies with different
      techniques. There are no controlled and randomized trials, and the few
      retrospective comparative cohort studies are limited by small numbers of patients
      and biased by historical controls of open surgery. Based on the available
      literature, there is no evidence that MIE brings clear benefits compared to
      conventional esophagectomy. Increasing experience and the report of larger series
      might change this scenario.

PMID- 20698042
TI  - Neoadjuvant treatment of esophageal cancer.
AB  - The management of esophageal cancer has been evolving over the past 30 years. In
      the United States, multimodality treatment combining chemotherapy and
      radiotherapy (RT) prior to surgical resection has come to be accepted by many as
      the standard of care, although debate about its overall effect on survival still
      exists, and rightfully so. Despite recent improvements in detection and
      treatment, the overall survival of patients with esophageal cancer remains lower
      than most solid tumors, which highlights why further advances are so desperately
      needed. The aim of this article is to provide a complete review of the history of
      esophageal cancer treatment with the addition of chemotherapy, RT, and more
      recently, targeted agents to the surgical management of resectable disease.

PMID- 20698045
TI  - Portal vein ligation accelerates tumor growth in ligated, but not contralateral
      lobes.
AB  - AIM: To investigate the mechanisms of liver growth and atrophy after portal vein
      ligation (PVL) and its effects on tumor growth. METHODS: Mice were subjected to
      PVL, partial hepatectomy, or sham surgery. The morphological alterations,
      activation of transcription factors, and expression of cytokines and growth
      factors involved in liver regeneration were evaluated. In a separate set of
      experiments, murine colorectal carcinoma cells were injected via the portal vein
      and the effect of each operation on liver tumor growth was studied. RESULTS:
      Liver regeneration after PVL and partial hepatectomy were very similar. In
      ligated lobes, various cytokines, transcription factors and regulatory factors
      were significantly upregulated compared to non-ligated lobes after PVL. Atrophy
      in ligated lobes was a result of early necrosis followed by later apoptosis.
      Tumor growth was significantly accelerated in ligated compared to non-ligated
      lobes. CONCLUSION: Tumor growth was accelerated in ligated liver lobes and
      appeared to be a result of increased growth factor expression.

PMID- 20698046
TI  - Decreased IgA+ plasma cells and IgA expression in acute liver necrosis mice.
AB  - AIM: To investigate the number of intestinal immunoglobulin A (IgA+) plasma cells
      and expression of intestinal IgA in mice with acute liver necrosis. METHODS: A
      model of acute liver necrosis was established by intraperitoneal injection of
      galactosamine (GalN) and lipopolysaccharide (LPS). Sixty mice were randomly
      divided into one of 4 equal groups: normal control, acute liver necrosis, LPS, or
      GalN. Hematoxylin and eosin staining, immunohistochemistry, and an enzyme-linked
      immunosorbent assay were employed to assess liver and intestinal injury, count
      intestinal IgA+ plasma cells, and measure the expression level of IgA and
      interferon gamma (IFN-gamma) in the small intestinal mucosa of mice. RESULTS:
      Injured intestinal mucosa was observed in the acute liver necrosis group but not
      in the normal, LPS or GalN groups. Compared with the normal group, intestinal
      IgA+ plasma cells were slightly decreased in the LPS and GalN groups [429 +/- 20
      per high power field (HPF), 406 +/- 18/HPF, respectively], whereas they were
      markedly decreased in the acute liver necrosis group (282 +/- 17/HPF vs 495 +/-
      26/HPF in normal group, P < 0.05). The expression of intestinal IgA was also
      slightly decreased in LPS and GalN groups, but was markedly reduced in the acute
      liver necrosis group as determined by enzyme-linked immunosorbent assay (P <
      0.05). In contrast, the level of IFN-gamma was slightly increased in LPS, GalN
      and acute liver necrosis groups, but with no statistical significance (P > 0.05).
      CONCLUSION: Intestinal IgA+ plasma cells and IgA expression levels indicating
      that mucosal immune barrier dysfunction, does exist in acute liver necrosis.

PMID- 20698047
TI  - Early ileocolonoscopy with biopsy for the evaluation of persistent post
      transplantation diarrhea.
AB  - AIM: To investigate the significance of ileocolonoscopy with histology in the
      evaluation of post-transplantation persistent diarrhea (PD). METHODS: We
      retrospectively reviewed all records of renal transplant patients with PD, over a
      3-year period. All patients were referred for ileocolonoscopy with biopsy,
      following a negative initial diagnostic work up. Clinical and epidemiological
      data were compared between cases with infectious or drug-induced diarrhea.
      RESULTS: We identified 30 episodes of PD in 23 renal transplant patients (1-3
      cases per patient). There were 16 male patients and the mean age at the time of
      PD was 51.4 years. The average time from transplantation to a PD episode was 62.3
      +/- 53.2 mo (range 1-199 mo). Ileocolonoscopy detected mucosal abnormalities in
      19 cases, whereas the intestinal mucosa appeared normal in 11 cases. Histological
      examination achieved a specific diagnosis in 19/30 cases (63.3%). In nine out of
      11 cases (82%) with normal endoscopic appearance of the mucosa, histological
      examination of blinded biopsies provided a specific diagnosis. The etiology of PD
      was infectious in 11 cases (36.6%), drug-related in 10 (33.3%), of other causes
      in three (10%), and of unknown origin in six cases (20%). Infectious diarrhea
      occurred in significantly longer intervals from transplantation compared to drug
      related PD (85.5 +/- 47.6 mo vs 40.5 +/- 44.8 mo, P < 0.05). Accordingly, PD due
      to drug-toxicity was rarely seen after the first year post-transplantation.
      Clinical improvement followed therapeutic intervention in 90% of cases.
      Modification of immunosuppressive regimen was avoided in 57% of patients.
      CONCLUSION: Early ileocolonoscopy with biopsies from both affected and normal
      mucosa is an important adjunctive tool for the etiological diagnosis of PD in
      renal transplant patients.

PMID- 20698048
TI  - Helicobacter pylori infection concomitant with metabolic syndrome further
      increase risk of colorectal adenomas.
AB  - AIM: To investigate the association of colorectal adenomas with both Helicobacter
      pylori (H. pylori) infection and metabolic syndrome. METHODS: Using a cross
      sectional hospital-based study, we analyzed physical examination data from 9311
      healthy subjects with overnight physical examinations performed between January
      2004 and December 2006. Examined data included gender, age, life style,
      anthropometric measurements, blood pressure, biochemical and hematological
      studies, H. pylori infection detected by esophagogastroduodenoscopy and biopsy
      urease tests, and colorectal adenomas detected with a complete total colonoscopy.
      RESULTS: The prevalence values for H. pylori infection, metabolic syndrome, and
      colorectal adenoma were 39.2%, 18.7%, and 20.7%, respectively. Colorectal adenoma
      risk factors included male gender [odd ratio (OR): 2.005, 95% confidence interval
      (CI): 1.740-2.310, P < 0.001], advanced age (OR: 1.046, 95% CI: 1.040-1.052, P <
      0.001), smoking (OR: 1.377, 95% CI: 1.146-1.654, P = 0.001), increased body fat
      (OR: 1.016, 95% CI: 1.007-1.026, P = 0.001), higher white blood cell count (OR:
      1.038, 95% CI: 1.005-1.073, P = 0.025), H. pylori infection (OR: 1.366, 95% CI:
      1.230-1.517, P < 0.001), and metabolic syndrome (OR: 1.408, 95% CI: 1.231-1.610,
      P < 0.001). In addition, concomitant H. pylori infection with metabolic syndrome
      further increased the probability of colorectal adenomas. CONCLUSION: Our study
      revealed H. pylori infection with concomitant metabolic syndrome might further
      increase the risk of colorectal adenomas.

PMID- 20698049
TI  - Germline mutation analysis of hPMS2 gene in Chinese families with hereditary
      nonpolyposis colorectal cancer.
AB  - AIM: To study the germline mutation of hPMS2 gene in 26 unrelated Chinese
      hereditary nonpolyposis colorectal cancer (HNPCC) probands and to fulfill the
      screening strategy for HNPCC in Chinese. METHODS: Genomic DNA was extracted from
      the peripheral blood. To avoid the interference of pseudogene in detection of the
      remaining 11 exons (exon 1-5, 9, 11-15), long-range polymerase chain reaction
      (PCR) was conducted to amplify the complete coding region of hPMS2 gene firstly.
      Then 1/8 of the PCR products were used as template to amplify the individual exon
      respectively and DNA sequencing was done. Direct DNA sequencing of the
      conventional PCR products of exon 6, 7, 8 and 10 of hPMS2 gene was performed. The
      same analysis was made in 130 healthy persons without family histories of HNPCC
      to further investigate the pathological effects of the detected missense
      mutation. RESULTS: One HNPCC proband fulfilled Bethesda guidelines and was found
      to carry the germline mutation of hPMS2 gene, which has not been reported in
      Chinese HNPCC families. It was a missense mutation at c.1532C>T of exon 11. It
      was detected in three controls as well with an occurrence rate of 2.3% (3/130).
      Since it could not be found in the PMS2-single nucleotide polymorphism (SNP)
      database, this missense mutation is a new SNP unreported up to date. Meanwhile,
      260 reported SNPs of hPMS2 gene were detected in the 26 HNPCC probands. The 2nd
      and 5th exons were probably the hot SNP regions of hPMS2 gene in Chinese HNPCC
      families involving 53.1% of all reported SNP. CONCLUSION: The germline mutation
      of hPMS2 gene may be rare in Chinese HNPCC families. The 2nd and 5th exons are
      hot SNP regions of hPMS2 gene.

PMID- 20698050
TI  - Poorly differentiated endocrine carcinoma of the pancreas responded to
      gemcitabine: Case report.
AB  - Poorly differentiated endocrine carcinoma (PDEC) of the pancreas is a rare and
      aggressive tumor. First-line treatment is commonly a combination of etoposide and
      cisplatin, but there is no consensus regarding further treatment recommendations.
      In this report, we describe a case of pancreatic PDEC treated with gemcitabine as
      third-line chemotherapy. A 62-year-old man with pancreatic PDEC was administered
      etoposide plus cisplatin as first-line treatment; he then received irinotecan for
      tumor relapse. However, because irinotecan induced ileus in this patient, we
      chose gemcitabine as third-line chemotherapy. After two cycles of gemcitabine
      (1000 mg/m(2) on days 1, 8 and 15 every 4 wk), a partial tumor response was noted
      by computed tomography (approximately 68% reduction in tumor size). Our patient
      survived for 15 mo after diagnosis. This is a rare case of unresectable
      pancreatic PDEC, which showed a partial response to gemcitabine after the failure
      of two other regimens. Gemcitabine could be an effective treatment option for
      pancreatic PDEC that is resistant to other treatments.

PMID- 20698051
TI  - Reply to "Application of contrast-enhanced intraoperative ultrasonography in the
      decision-making about hepatocellular carcinoma operation".
AB  - The use of contrast-enhanced intraoperative ultrasound for hepatocellular
      carcinoma has been already proposed as a novel technique to stage the disease
      during surgical resection. In the herein presented "letter to the editor", the
      authors underline some important points, which have been raised following paper
      published in the January issue of World Journal of Gastroenterology.

PMID- 20698052
TI  - Bibliography. Sarcoidosis. Current world literature.

PMID- 20698053
TI  - Bibliography. Interstitial lung disease. Current world literature.

PMID- 20698054
TI  - Micronutrient intake and breast cancer characteristics among postmenopausal
      women.
AB  - Few studies on micronutrients and postmenopausal breast cancer have examined the
      association with breast cancer characteristics. The aim of this study was to
      investigate the associations between vitamin C, vitamin E, folate and beta
      carotene from diet and supplements and risk of postmenopausal breast cancer
      subtypes defined by histology (ductal/lobular), estrogen receptor (ER) and
      progesterone receptor (PGR) status. In a prospective cohort study of 26,224
      postmenopausal women information on diet, supplements and lifestyle was collected
      through questionnaires. One thousand seventy-two cases were identified during
      follow-up. Incidence rate ratios of total breast cancers and breast cancer
      subtypes related to micronutrient intake were calculated using Cox proportional
      hazard analyses. This study found no association between overall breast cancer
      and any micronutrients, while some effects were shown when stratifying by breast
      cancer subtypes: dietary but not supplemental beta-carotene showed a protective
      effect against lobular breast cancer [incidence rate ratio (IRR): 0.72; 95%
      confidence interval (CI): 0.57-0.91]. Dietary vitamin E was associated with
      decreased risk of ER and PGR positive breast cancer (IRR: 0.50; 95% CI: 0.25
      0.98) and dietary folate was associated with increased risk of ER and PGR
      positive breast cancer (IRR: 1.27; 95% CI: 1.03-1.95). This study found no effect
      of micronutrients on overall risk of postmenopausal breast cancer, but indicated
      possible effects of micronutrients in subgroups of breast cancer, with a
      potential beneficial effect of dietary beta-carotene in lobular breast cancer and
      dietary vitamin E in ER + PGR+ breast cancer and a potential harmful effect of
      dietary folate in ER+ PGR+ breast cancer.

PMID- 20698055
TI  - Aspirin and risk of endometrial cancer: a case-control study from Italy.
AB  - Data on the role of aspirin on endometrial cancer risk are scanty. Here we
      provide additional information on the issue, using data from a multicentric
      Italian case-control study. The study was conducted between 1992 and 2006 in
      three Italian areas, on 442 cases with histologically confirmed endometrial
      cancer and 676 control women admitted to the same hospitals as cases for a wide
      spectrum of acute, non-neoplastic, non-gynaecological, non-hormone-related
      conditions, providing information on aspirin use. Odds ratios (OR) of endometrial
      cancer and corresponding 95% confidence intervals were calculated using multiple
      logistic regression models, including terms for sociodemographic characteristics,
      body mass index and hormonal and reproductive factors. Regular aspirin use was
      reported by 28 (6.3%) cases and 46 (6.8%) controls, corresponding to a
      multivariate OR of 0.65 (95% confidence interval 0.37-1.11). There was no
      consistent pattern of risk with duration of use, nor with age at first use, time
      since first use or time since last use. Further, there was no difference in risk
      estimates across strata of body mass index. This study--the first one from a
      population outside North America--adds relevant information on the absence of a
      consistent association between aspirin use and endometrial cancer risk, even in
      high-risk overweight and obese women.

PMID- 20698056
TI  - UK: price-based promotions target poor.

PMID- 20698057
TI  - Bangladesh: women feature in new cigarette ads.

PMID- 20698058
TI  - New research findings on adolescent reproductive health in Africa.

PMID- 20698059
TI  - Protecting the next generation: promising directions for a better future.

PMID- 20698060
TI  - Improving health, improving lives: impact of the African Youth Alliance and new
      opportunities for programmes.
AB  - The African Youth Alliance (AYA) was a partnership to improve adolescent sexual
      and reproductive health, and prevent HIV/AIDS in Botswana, Ghana, Tanzania and
      Uganda. The AYA model was a comprehensive range of integrated interventions,
      implemented concurrently and at scale using a multi-sectoral approach. AYA was
      funded for five years (2000-2005) with $56.7 million from the Bill and Melinda
      Gates Foundation. Over 35,000,000 stakeholders were reached through media
      campaigns, almost 400,000 young people received Life Planning Skills training,
      and over 2,500,000 visits were made by young people to static clinics and
      outreach services. A post-test evaluation was conducted by John Snow Inc. (JSI)
      in 2006 and combined case-control and self-reported exposure design. Case-control
      design data were analyzed using Propensity Score Matching (PSM), and the Self
      Reported Exposure design data were analyzed using PSM and Instrumental Variable
      (two-stage regression) (IV). The results show AYA's significant and positive
      treatment effects on sexual knowledge, attitudes, and behaviours. The research
      suggests a comprehensive, multi-component approach such as AYA's can be effective
      in improving some key ASRH variables.

PMID- 20698061
TI  - Is poverty a driver for risky sexual behaviour? Evidence from national surveys of
      adolescents in four African countries.
AB  - This paper contributes to conflicting evidence on the link between poverty and
      risky sexual behaviour by examining the effect of wealth status on age at first
      sex, condom use, and multiple partners using nationally representative
      adolescents' data from Burkina Faso, Ghana, Malawi, and Uganda. The results show
      that the wealthiest girls in Burkina Faso, Ghana, and Malawi had later sexual
      debut compared with their poorer counterparts but this association was not
      significant for Uganda. Wealth status was weaker among males and significant only
      in Malawi, where those in the middle quintile had earlier sexual debut. Wealthier
      adolescents were most likely to use condoms at the last sexual act, but wealth
      status was not associated with number of sexual partners. Although the link
      between wealth status and sexual behaviour is not consistent, there is evidence
      that poor females are vulnerable to infection because of earlier sexual debut and
      non-use of condoms.

PMID- 20698062
TI  - Influence of social connectedness, communication and monitoring on adolescent
      sexual activity in Ghana.
AB  - This paper examines connectedness to, communication with and monitoring of
      unmarried adolescents in Ghana by parents, other adults, friends and key social
      institutions and the roles these groups play with respect to adolescent sexual
      activity. The paper draws on 2004 nationally-representative survey data and
      qualitative evidence from focus group discussions and in-depth interviews with
      adolescents in 2003. Adolescents show high levels of connectedness to family,
      adults, friends, school and religious groups. High levels of adult monitoring are
      also observed, but communication with family about sex-related matters was not as
      high as with non-family members. The qualitative data highlight gender
      differences in communication. Multivariate analysis of survey data shows a strong
      negative relationship between parental monitoring and recent sexual activity for
      males and females, and limited effects of communication. Creating a supportive
      environment and showing interest in the welfare of adolescents appear to promote
      positive sexual and reproductive health outcomes.

PMID- 20698063
TI  - [Judiciary astrology and sphere for physicians. Valladolid 1599].

PMID- 20698064
TI  - Help for tinnitus sufferers.

PMID- 20698077
TI  - [Regional meetings of the Japanese Association of Anatomists. Japan. 2010.
      Abstracts].

PMID- 20698076
TI  - Guidelines for management of nonalcoholic fatty liver disease: an updated and
      revised edition.

PMID- 20698078
TI  - Impact of statin therapy on survival in epithelial ovarian cancer.
AB  - OBJECTIVE: 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase inhibitors, or
      statins, are common therapeutic agents in the management of dyslipidemias.
      Epidemiologic and pharmacologic data also suggest statins have an effect on
      cancer biology. We sought to determine the association between use of statins and
      epithelial ovarian cancer survival, disease progression, and clinico-pathologic
      factors. METHODS: After IRB approval, we performed a retrospective review of all
      patients with advanced stage (III/IV) epithelial ovarian or primary peritoneal
      cancer undergoing primary cytoreductive surgery by a gynecologist oncologist
      between 6/1996 and 6/2001. Abstracted data included statin use at time of initial
      cytoreductive surgery, as well as clinico-pathologic factors and survival.
      Statistical analysis included Fisher's exact test, Kaplan-Meier survival, and Cox
      regression analyses. RESULTS: 126 patients met criteria for review. Seventeen
      (14%) patients were undergoing concurrent statin therapy at time of initial
      cytoreductive surgery. Statin users were statistically older (median age 67
      years, versus 60 years for non-users, p=0.002) and had a greater incidence of
      diabetes mellitus (18% versus 3% in non-users, p=0.03). Of the entire cohort, 21
      patients (17%) were suboptimally cytoreduced after initial surgery, with residual
      disease N1 cm; statin use did not correlate with incidence of optimal resection
      (p=0.3). Median progression-free survival for statin users was 24 months,
      compared to 16 months for statin non-users (p=0.007). Similarly, overall survival
      was significantly longer for statin users (62 months) compared to statin non
      users (46 months, p=0.04). Multivariable analysis identified statin use as an
      independent positive prognostic factor, after controlling for age, stage, grade,
      and suboptimal cytoreduction (p=0.02). CONCLUSIONS: These data indicate statin
      use in patients diagnosed with epithelial ovarian cancer is associated with
      improved survival, and suggest a potential suppressive impact of HMG-CoA
      reductase inhibitors on tumor biology. Studies are proposed to explore the
      molecular mechanisms underlying these clinical observations.

PMID- 20698079
TI  - [Considerable delay in diagnosis and acute management of subarachnoid
      haemorrhage].

PMID- 20698080
TI  - Cancer genetics. Introduction.

PMID- 20698082
TI  - Open source expected to improve innovation.

PMID- 20698081
TI  - The door that Freud reopened.

PMID- 20698083
TI  - Sestre milosrdnice University Hospital. Historical review.

PMID- 20698084
TI  - From competence to waive counsel to competence to represent oneself: the Supreme
      Court advances fairness in Edwards.

PMID- 20698085
TI  - The Joint Commission awards first heart failure advanced certification.

PMID- 20698086
TI  - Protecting organizations' confidential accreditation information.

PMID- 20698087
TI  - APPROVED: Decision rule for a preliminary denial of accreditation eliminated.

PMID- 20698089
TI  - APPROVED: New perinatal care core measure set available April 2010.

PMID- 20698090
TI  - APPROVED: New preliminary denial of accreditation process.

PMID- 20698091
TI  - Joint Commission anticipates more discussion on physician.

PMID- 20698093
TI  - Health care organizations can report privacy concerns to Joint Commission.

PMID- 20698092
TI  - Approved: revisions to requirements for critical access hospitals with distinct
      part units.

PMID- 20698094
TI  - Clarification: site marking under the universal protocol.

PMID- 20698095
TI  - HHS Report: Infection prevention professionals, hospital representatives
      recommend steps to simplify and streamline federal HAI tracking system.

PMID- 20698096
TI  - Can lean save lives?
AB  - PURPOSE: The purpose of this paper is to show how over the last 18 months Bolton
      Hospitals NHS Trust have been exploring whether or not lean methodologies, often
      known as the Toyota Production System, can indeed be applied to healthcare.
      DESIGN/METHODOLOGY/APPROACH: This paper is a viewpoint. FINDINGS: One's early
      experience is that lean really can save lives. The Toyota Production System is an
      amazingly successful way of manufacturing cars. It cannot be simply translated
      unthinkingly into a hospital but lessons can be learned from it and the method
      can be adapted and developed so that it becomes owned by healthcare staff and
      focused towards the goal of improved patient care. ORIGINALITY/VALUE: Working in
      healthcare is a stressful and difficult thing. Everyone needs a touch of
      inspiration and encouragement. Applying lean to healthcare in Bolton seems to be
      achieving just that for those who work there.

PMID- 20698097
TI  - Can Six Sigma be the "cure" for our "ailing" NHS?
AB  - PURPOSE: The purpose of this research is to analyse whether Six Sigma business
      strategy can be used to improve the financial and operational performance of the
      NHS. The paper will also look at some of the major challenges and barriers in the
      implementation of this powerful process improvement strategy within the
      healthcare sector. DESIGN/METHODOLOGY/APPROACH: This paper discusses whether Six
      Sigma DMAIC methodology can be a useful and disciplined approach to tackle
      process- and quality-related problems in the NHS. FINDINGS: The paper presents
      some key findings from other researchers in the field, followed by some comments
      on whether Six Sigma is a useful approach to be considered by the NHS for cost
      reduction and defect reduction strategies. ORIGINALITY/VALUE: The paper
      illustrates the point that Six Sigma is not confined just to manufacturing
      industry, rather it is equally applicable to service industry, especially the
      healthcare and financial sectors. The application of Six Sigma in the UK health
      sector is relatively new and the purpose of the paper is to increase the
      awareness of this powerful business strategy in healthcare discipline.

PMID- 20698098
TI  - Health service improvement through diagnostic waiting list management.
AB  - PURPOSE: The purpose of this research is to focus on a hospital Division of
      Diagnostics and Clinical Support (150 medical, 1975 non-medical staff) and how
      systems were enhanced through lean principles application to facilitate quality
      and performance improvement. DESIGN/METHODOLOGY/APPROACH: An action research
      methodology was adopted. The research involved: review of available performance
      and quality improvement literature; identification of the systems that required
      improvement; adoption and implementation of new working methods. FINDINGS: The
      results were recognised as being beneficial to all parties, especially the
      patients! Staff recognised the need for change; the process transformation was
      actually welcomed. Patient waiting times reduced from 26 to 13 weeks. Fast
      track/"query cancer" service for out-patients now within ten days; the majority
      of in-patients receive imaging within 72 hours. Ultimately, patients are
      diagnosed faster and treatment commences earlier. Departmental managers can
      effectively manage capacity to meet demand because they now understand the
      waiting "profile". RESEARCH LIMITATIONS? IMPLICATIONS: The methodology applied
      was appropriate, generating data to facilitate discussion and from which to draw
      conclusions. A perceived limitation is the single case approach; however, Remenyi
      et al. argue that this can be enough to add to the body of knowledge. PRACTICAL
      IMPLICATIONS: Guidelines indicating "What went well?" and "What could have gone
      better?" were produced. These centred on the practical application aspects. The
      implementation methodology developed is being used elsewhere within the same
      hospital group. ORIGINALITY/VALUE: The paper demonstrates that the application of
      improvement techniques, such as "Lean", can focus efforts to improve performance.
      This is of value to those working in the UK healthcare and wider public sector.

PMID- 20698099
TI  - Should doctors stop taking the generic history? A comparison of house officers'
      and nursing staff clerking in general surgery.
AB  - PURPOSE: The purpose of this paper is to show how the implementation of the
      European Working Time Directive in August 2004 has dramatically decreased junior
      doctors' working hours, as a consequence of which new ways of working will need
      to be found. Traditionally both doctors and nurses record the same generic
      history (past medical history, social and family history, drug history and
      allergies) in their own notes. This is unnecessary duplication and maybe only
      nursing staff should record this information. This study is undertaken to
      identify the differences between junior doctors' and nurses' clerking to assess
      whether they are comparable. DESIGN/METHODOLOGY/APPROACH: A prospective study of
      100 case notes from elective and emergency admissions was undertaken. The
      completeness of various parts of the history and the recording of the vital signs
      were compared between nurses and house officers. FINDINGS: The Past Medical
      History was complete in only 30 per cent of the house officers' notes and 42 per
      cent of nursing records. The social history was complete in all the nursing
      records but only 35 per cent of the doctors' notes. Nurses recorded a complete
      personal history more than doctors (62 per cent v. 13 per cent respectively). The
      drug history was poorly recorded in house officers' notes, being complete in 22
      per cent, whereas this was complete in 73 per cent of nursing records. The record
      of the history of allergies was poor in both groups at just over 10 per cent.
      Finally 87 per cent of nurses managed to record vital signs but these were
      missing from nearly half of the house officers' notes. ORIGINALITY/VALUE: The
      study has shown that details of the generic medical history are recorded more
      completely by the nursing staff and only they should record this information.
      This will allow junior doctors more time to deal with the increased demands and
      reduced hours of work.

PMID- 20698100
TI  - Fine needle aspiration cytology in the evaluation of parotid gland tumors.
AB  - Main objective of this study was to evaluate the usefulness and accuracy of fine
      needle aspiration cytology (FNAC) diagnosis of parotid masses to distinguish
      reliably between benign and malignant lesions. In the period of 5 years, 214
      parotid glands were resected at the Rijeka University Hospital Center (Croatia),
      but 176 patients had cytopathological and histopathological diagnoses and
      therefore fulfilled the criteria for study. The results of the FNAC were analyzed
      and compared to the corresponding histopathological diagnosis obtained from the
      surgical specimen. Histological evaluation revealed 17malignant and 159 benign
      lesions. There were 13 true positive, 147 true negative, 3 false negative, and 13
      false positive. Sensitivity of FNAC was 81%, and specificity was 98%. FNAC
      results provide useful predictive preoperative information and better preparation
      the surgeon and patient for surgical procedure.

PMID- 20698101
TI  - Malignancy risk assessment in adenomatoid nodules and suspicious follicular
      lesions of the thyroid obtained by fine needle aspiration cytology.
AB  - Our aim was to assess malignancy risk in adenomatoid nodules and suspicious
      follicular lesions of the thyroid obtained by fine needle aspiration (FNA)
      cytology. Retrospective research was performed of 276 patients who underwent
      thyroid surgery after preoperative ultrasound-guided FNA diagnosis of either
      adenomatoid nodule, cellular follicular lesion, "suspicious for follicular
      neoplasm" or follicular neoplasm. Out of 276 patients, FNA reports showed 15
      diagnoses (5%) of adenomatoid nodules, 73 (26%) cellular follicular lesions, 76
      (28%) "suspicious for follicular neoplasm", and 112 diagnoses (41%) of follicular
      neoplasm. FNA reports were compared with pathohistological findings. In FNA
      reports of adenomatoid nodule (N = 15), there were seven (47%) pathohistological
      diagnoses (PHDs) of nodular goiter, and eight (53%) PHDs of follicular adenoma.
      In FNA reports of cellular follicular lesion (N = 73), there were 2 (3%) PHDs of
      thyroiditis, 32 (44%) PHDs of nodular goiter, 38 (52%) PHDs of follicular
      adenoma, and one (1%) PHD of papillary carcinoma. In FNA reports of "suspicious
      for follicular neoplasm" (N = 76), there was one (1%) PHD of thyroiditis, 24
      (32%) PHDs of nodular goiter, 47 (62%) PHDs of follicular adenoma and four (5%)
      diagnoses of papillary carcinoma. In FNA reports of follicular neoplasm (N =
      112), there were 25 (22%) PHDs of nodular goiter, 72 (64%) PHDs of follicular
      adenoma, and 15 (14%) PHDs of thyroid carcinoma. We found significant difference
      (p < 0.01) between investigated FNA report groups according to malignancy risk.
      Stratification of cytologic diagnoses of follicular thyroid lesions into
      different subcategories with various probabilities of malignancy allows more
      accurate estimation of malignancy risk and individualized patient treatment, when
      deciding between immediate operation and close follow-ups with repeat FNA.

PMID- 20698102
TI  - A correlative study of histology and imprint cytology of gastric mucosa biopsy in
      the diagnosis gastric cancer.
AB  - The purpose of this paper is to show the importance of gastric mucosa imprint
      cytology in detecting stomach cancer. Analyzed were 364 cytological and
      pathohistiological samples taken from 335 patients having suspected diagnosis of
      gastric cancer. Every specimen was submitted to slide imprinting and then fixed
      in formalin for further processing with routine histopathology. The imprints were
      air dried for cytological analysis, stained according to May-Grunwald-Giemsa and
      analyzed by light microscope. By pathohistological punch-biopsy samples analysis
      stomach cancer was found in 45 samples. With cytological samples analysis the
      cancer was detected in 48 samples and 13 cytological samples were suspected of
      cancer With combining these two methods cancer was found in 68 cases. Patients
      with positive cytological finding and negative pathohistologic finding underwent
      gastroscopy with punch-biopsy. All patients with positive pathohistological
      findings were operated. All materials were histologically examined. Cancer was
      found in 68 patients. Cytological analysis of stomach mucosa bioptic material
      imprints, increases the number of positive findings in preoperative stage of
      gastric cancer diagnosis. The greatest advantage of this method is short period
      for preparation of material, simplicity and low price. Every data on
      morphological changes in mucosa has been also pathohistologically checked,
      because taking imprints does not damage the specimen.

PMID- 20698103
TI  - Flow cytometry immunophenotyping (FCI) of fine needle aspirates (FNAs) of lymph
      nodes.
AB  - Flow cytometry immunophenotyping (FCI) has an important role in the clinic work
      up of fine needle aspirates (FNAs) of lymph nodes. Its standardization has been
      defined by proposed analytical protocols and procedures used to assure proper
      analytical results also in those non-routine samples. In Institute of Clinical
      Chemistry, "Merkur" University Hospital, FCI is accredited method according to
      laboratory accreditation standard ISO 15189. According to this laboratory
      accreditation standard, participation in external quality assessment (EQA)
      programs is a prerequisite for assuring integrity and quality of the entire
      laboratory process. A critical analysis of our institutional experience in the
      feasibility of FCI of the material obtained by FNA of lymph nodes with suspected
      lymphoma represented the purpose of the study. During an eight-year period in
      Institute of Clinical Chemistry, "Merkur" University Hospital, a total of 1295
      FNA analysis was done, 245 of them with a possible diagnosis of B-cell Non
      Hodgkin lymphomas (B-NHL) formed the basis of the study. Lymphocytes were
      isolated on density gradient according to Boyum et al. The average feasibility of
      FNAs for FCI analysis was 86% (ranged 78-93%). An acceptable total cell number in
      FNAs for FCI analysis (4257) was established. In total population of respondents
      statistical significances in expressions of cellular antigens CD3, CD5, CD22,
      CD23, CD19 and CD5 on B-cells (CD5+CD19+) between patient's with final diagnosis
      of benign, reactive lymphoid proliferations and patient's with diagnosis of B-NHL
      were found. EQA results analysis showed that all results were either inside
      target values (X +/- 1SD) or inside accepted values (X +/- 2SD). Compatibility of
      the restriction of immunoglobulins light chains determinated by FCI and
      cytomorphology diagnosis depends on the choice of criterion values of the light
      chains ratio which determine the monoclonality. According to the matrix of shares
      of all classified data of retained neural network, ranges of diagnostic
      sensitivity, specificity, positive predictive value (PPV), negative predictive
      value (NPV) and prevalency of 82%, 72%, 93%, 48%, and 72% were produced. As a
      conclusion, FCI is a reliable methodology for phenotyping FNAs of lymph nodes
      with suspected B-NHLs detecting their clonality easily.

PMID- 20698104
TI  - Multimodal image analysis of chronic leukemic lymphoproliferative disorders and
      the hypothesis of "single" and "multiple" programmed stops in the development of
      typical and atypical forms of leukemias and lymphomas.
AB  - The study consisted of morphometric analysis, assessment of the argyrophilic
      nucleolar organization region (AgNOR) characteristics, and image cytometry (ICM)
      in different tumor mass compartments: bone marrow (BM), peripheral blood (PB) and
      lymph nodes (LN) from patients with chronic leukemic lymphoproliferative
      disorders. A total of 71895 cells were analyzed on SFORM PC (VAMSTEC, Zagreb).
      Correlation between morphometric, AgNOR and ICM characteristics revealed the
      cells with low proliferative activity to possess small, homogeneous AgNOR, with
      the majority of cells in the peak of DNA histogram. The cells with high
      proliferative activity had inhomogeneous AgNOR, mostly containing greater DNA
      content than peak cells, pathologic mitoses (DNA > 4N), or the majority of cells
      were in the S-phase of the cell cycle. Cells with medium proliferative activity
      and annular AgNOR were in-between. Analysis of different tumor mass compartments
      showed that lymphatic cells with the affinity to accumulate in BM regularly
      exhibited low proliferative activity (a lower percentage of cells in SFC and
      highest percentage of cells in the peak of the G0/G1 phase). The cells in LN
      exhibited the characteristics of proliferative cells (an increased number of
      AgNOR, larger and more proliferative inhomogeneous AgNOR, and lowest percentage
      of cells in the G0/G1 phase). The migration of cells from BM to LN and between
      lymph nodes occurred through PB (there were cells with low and high proliferative
      activity: a higher proportion of cells in SFC and at the same time in the G0/G1
      phase of the cell cycle). Analysis of cell size and proliferative activity in
      different compartments of tumor mass revealed that the cells in BM and PB did not
      differ substantially according to size and proliferative activity, while an
      inverse pattern was observed between PB and LN. As small cells are inactive and
      larger cells more proliferative, the analysis quite unexpectedly showed the PB
      cells to be largest and most inactive, in contrast to LN where the cells were
      smallest and most active. The "single" and "multiple programmed stops" have been
      hypothesized in the development of typical forms of leukemias and lymphomas and
      atypical forms of subacute and subchronic leukemias. Differentiation impairment
      may occur at any stage, and different "stop" locations result in different
      morphology and affinity to accumulation in bone marrow, peripheral blood and
      lymph nodes.

PMID- 20698105
TI  - Flow cytometric analysis of deep-seated lymph nodes.
AB  - Flow cytometry (FC) immunophenotyping is an important tool in the evaluation of
      lymphadenopathy and is widely used in the diagnosis of non-Hodgkin's lymphomas
      (NHLs) on fine-needle aspirates of lymph nodes and extranodal sites. Because at
      least 80% of NHLs are of B-cell type, detection of immunoglobulin (Ig) light
      chain-restriction is the most commonly used method for confirmation of
      monoclonality. The aim of our study was to evaluate usefulness of endoscopic
      ultrasound-guided fine needle aspiration (EUS-FNA) for FC analysis from deep
      seated lymph nodes and to compare results of FC clonality analysis to
      cytomorphologic diagnosis of sampled lymph nodes. For cytological diagnosis
      direct smears were made, selected slide was stained for rapid-on site evaluation
      procedure. Sixteen patients with suspected NHL of deep-seated lymph nodes
      obtained by EUS-FNA were submitted for FC clonality analysis using four-color
      multiparameter flow cytometry stained with kappa/lambda/CD19/CD45. Clonality
      analysis was performed on 11 samples. Monoclonality was demonstrated in seven of
      11 cases cytologically diagnosed as NHL and four of 11 cases cytologically
      diagnosed as benign were polyclonal. Our results show that EUS-FNAC with FC is a
      sensitive and specific tool in the diagnosis of deep-seated B-NHL. Cytologic
      diagnosis combined with FC clonality analysis can be performed in majority of
      cases and may eliminate need for open biopsy in some cases.

PMID- 20698106
TI  - Role of fine needle aspiration cytology in management of hepatocellular
      carcinoma: a single centre experience.
AB  - Hepatocellular carcinoma (HCC) mostly occurs in chronic liver disease and
      cirrhosis. Liver resection and liver transplantation (LT) represent potentially
      curative treatments of choice and if not feasible, palliative strategies such as
      percutaneous interventional techniques (PITs) and chemotherapy (ChT) are
      considered. Elevated alfa-fetoprotein, typical imaging pattern, needle core
      biopsy (NCB) and fine needle aspiration cytology (FNAC) complement diagnostic
      assessment of HCC. We have retrospectively analyzed all patients with
      contraindications for NCB in which HCC was diagnosed by FNAC during consecutive 5
      years in our hospital. Ultrasound guided FNAC provided a safe method of approach
      and, except for mild transitory discomfort at the site of puncture, no
      complications were documented. The diagnosis was established on May-Grunwald
      Giemsa (MGG) stained aspirates and additional immunocytochemistry. Of our 62
      patients, HCC developed in 61.3% cirrhotic and 38.7% non-cirrhotic livers. In the
      setting of cirrhosis 18.4% of patients underwent LT, 15.8% PITs, 26.3% ChT and
      39.5% symptomatic therapy. In non-cirrhotic setting 46% of patients underwent
      liver resection, and PIT, ChT and symptomatic therapy were applied in 4%, 25%,
      25% of cases, respectively. Pathohistology of resected and explanted livers (18
      cases) confirmed the initial diagnosis made on FNAC. Since only early stage of
      HCC has a better prognosis, every effort should be made to establish prompt and
      accurate diagnosis. Our observations demonstrate that FNAC offers minimally
      invasive, rapid and uncomplicated diagnostic approach, with sensitivity from 67%
      to 93% and specificity from 96% to 100%. FNAC, is of utmost importance in the
      setting of abnormal coagulation tests and ascites commonly seen in advanced liver
      disease, facilitating diagnostic workup and treatment decisions.

PMID- 20698107
TI  - Recurrent chromosomal abnormalities in lymphomas in fine needle aspirates of
      lymph node.
AB  - The detection of specific chromosomal abnormalities is important in the
      diagnostic workup of aggressive lymphomas, giving its impact on the treatment
      strategies and prognosis. This has been accomplished by using the fluorescent in
      situ hybridisation method (FISH) performed on fine needle aspiration (FNA)
      specimens what is attractive in the diagnosis of lymphoma in the comparation with
      other methods for collecting samples. The cytogenetic analyses were performed in
      series of 80 patients with lymphoma (43 women and 37 men, median age 48, range 3
      90 years). In our series 89.0% (71) of the specimens yield sufficient numbers of
      analysable metaphases, comprising 63 non-Hodgkin lymphomas (NHL) and 8 examples
      of Hodgkin disease (HD). Among 71 successful karyotyped specimens 58 (82.0%)
      showed clonal karyotypic abnormalities. Numerical changes in 4, structural
      changes in 20 and both and numerical with structural changes in 30 of 54 NHL
      cases. Trisomies 3, 7, 8, 12, 18, X and monosomies 1 were most common numerical
      abnormalities. The NHL cases were typically characterised by structural rather
      than numerical aberrations with chromosome arms 1p/q, 3p/q, 6q, 11q, 17p and 14q
      most frequently involved. The expected translocation (14;18) (q32;q21) in 8 and
      t(8;14) (q24;q34) in 6 cases, both translocations at the same time in three
      cases, complex rearrangement with chromosome 8, 14, and 18, namely t(8;14;18)
      (q24;q32;q21) in one case, t(11;14) (q13;q32) in three and one case with
      translocation 14q32 with chromosome 3q27, 6q and 14q32 were found. In 28 of 54
      (52%) NHL cases t(14;v) was present. Four abnormal clones detected in Hodgkin
      disease were typically consisted of a small percentage of metaphases. The use of
      FISH method enable the detection of loss or gain of genetic material and reveal
      rearrangements unsuspected by conventional cytogenetics in 34 (48.0%) cases.

PMID- 20698108
TI  - Is the HSIL subclassification cytologically real and clinically justified?
AB  - The aim of the study was to evaluate the justification of Croatian modification
      of Bethesda classification after thirteen years of its application, answering the
      question if the subclassification of high-grade squamous intraepithelial lesion
      (HSIL) into cervical intraepithelial lesion (CIN) grade 2 (CIN2) and grade 3
      (CIN3) is cytologically real and clinically justified. The retrospective study
      included 3110 women to whom cervical intraepithelial lesion of different grade
      was diagnosed by cytological examination of vaginal-cervical-endocervical (VCE)
      smear at Department of Clinical Cytology, Clinical hospital Osijek in period from
      1993 to 2005. 57.1% of women were monitored cytologically and colposcopically,
      while 42.9% of them had also pathohistological examination. The spontaneous
      regression of cytological finding was noted in 66.3% of the cases. Moderate
      dysplasia regressed more often (50.98%) than severe dysplasia (31.3%) and more
      rarely than mild dysplasia (70.1%), which was statistically significant (p <
      0.05). Comparing the first and the most serious cytological diagnosis during
      monitoring, it was found that mild dysplasia was also the most serious diagnosis
      in 80.1% of the cases, while in 19.9% of patients the initial diagnosis
      progressed into more severe lesion. Moderate dysplasia was also the most serious
      cytological diagnosis in 65.35% of the cases, while it progressed in severe
      dysplasia in 34.1% of the cases. Moderate dysplasia progressed more often into
      severe dysplasia than mild dysplasia (34.1% vs. 12.7%), which was statistically
      significant (p < 0.05). Positive predictive value of differential cytological
      diagnoses mild (23.7%), moderate (40.3%) and severe (90.1%) dysplasia calculated
      in relation to histological CIN3+ statistically significantly increases for every
      single diagnosis. Moderate dysplasia and severe dysplasia differ statistically (p
      > 0.05) in their biological behaviour and histological finding. In fact, 50.9% of
      moderate dysplasia spontaneously regressed, 14.4% persisted during follow-up, and
      59.7% had a histological finding milder than CIN3. Therefore, in almost 65% of
      moderate dysplasia lesions it is not justified to apply the same diagnostic
      therapeutic procedures as for severe lesions, which means that cytological
      subclassification of HSIL into moderate dysplasia and severe dysplasia lesions is
      clinically justified. Positive predictive value of differential cytological
      diagnoses mild, moderate and severe dysplasia calculated in relation to
      histological CIN3+ statistically significantly increases for every single
      diagnosis, which also confirms that moderate dysplasia can be individual
      diagnostic category, thus the subclassification of HSIL is cytologically
      possible.

PMID- 20698109
TI  - Cytology of cervical intraepithelial glandular lesions.
AB  - Cytological criteria for the identification of glandular intraepithelial lesions
      (GIL) have not yet been fully described, especially for the precursors of
      adenocarcinoma in situ (AIS), thus these lesions may frequently remain
      unrecognized. As most patients diagnosed with AIS or mild to moderate GIL (grades
      I, II) are free from clinical symptoms, cytology has a very responsible role in
      the detection of these lesions. The aim of the study was to achieve the most
      appropriate cytologic diagnosis of intraepithelial lesions of endocervical
      columnar epithelium, analyzing the cytology findings in patients with
      histologically verified AIS and GIL (I, II). The value of cytology in the
      detection and differential diagnosis was assessed in 123 patients with definitive
      histologic diagnosis of glandular lesions (AIS, n = 13; GIL I, n = 11; and GIL
      II, n = 7), and glandular lesions associated with squamous component (AIS
      associated with cervical intraepithelial neoplasia (CIN) or invasive squamous
      cell carcinoma (SCC), n = 58; GIL I or GIL II associated with CIN, n = 28; and
      GIL associated with microinvasive squamous carcinoma (MIC), n = 6). In 95.1% of
      patients, lesions were detected by cytologic analysis that indicated additional
      diagnostic procedure. In terms of differential diagnosis, cytology showed higher
      accuracy in predicting lesion severity vs. type of epithelial alteration (75.6%
      vs. 55.3%) and abnormalities of columnar epithelium (95.7%; vs. 74.2%). The
      accuracy of cytology was higher in pure (AIS, 61.5% and GIL I, II, 22.2%) than in
      mixed lesions (25.9% and 20.6%). Continuous improvement in cervical specimens and
      cytodiagnostic skills, better understanding of intraepithelial adenocarcinoma and
      precursors, and their inclusion in the classification of cytologic and histologic
      findings are expected to upgrade the detection of these lesions, and to reduce
      the invasive cervical adenocarcinoma morbidity and mortality.

PMID- 20698110
TI  - Serum immunoglobulins in non-Hodgkin's lymphoma patients.
AB  - Serum proteins and immunoglobulin (Ig) findings in 119 non-Hodgkin's lymphoma
      (NHL) patients were analysed. Out of them 96 (81%) patients had B non-Hodgkin
      lymphoma (B-NHL), and 23 (19%) T-NHL. Indolent type of NHL was more frequent (77
      patients, 65%), then aggressive type of NHL (42 patients, 35%). Most patients had
      normal serum protein concentration, the increased protein concentration was seen
      in 17% of patients while decreased concentration was noticed in 7% of patients.
      Hypoalbuminaemia was more frequent (43%) then hyperalbuminaemia (1%). In contrast
      to albumin, low levels of other protein fractions (alpha1-, alpha2-, and beta
      globulin) were rather rare (0.6%, 4%, and 3% of patients, respectively) and high
      levels were frequent (23%, 37%, and 8%, respectively). Polyclonal
      hyperimmunoglobulinaemia was more frequent finding than hypoimmunoglobulinaemia.
      In 29% patients higher IgG level and in 25% patients higher IgA level were found.
      IgM hypoimmunoglobulinaemia (22%) was more frequent than IgG (11%) and IgA (8%)
      hypoimmunoglobulinaemia. M-spike in serum protein electrophoresis was found in 11
      (7%) patients. The statistically significant association was not found between
      serum Ig concentration and lymphoma malignancy grade as well as between serum Ig
      concentration and immunologic origin of lymphoma. T-NHL patients have more often
      IgA concentration level above or under normal values than B-NHL patients (p <
      0.05).

PMID- 20698111
TI  - Primary gastrointestinal non-Hodgkin lymphoma in adults: clinicopathologic and
      survival characteristics.
AB  - Primary non-Hodgkin lymphomas of gastrointestinal tract (PGI-NHL) are the most
      common extranodal lymphomas with an increasing incidence. The incidence,
      clinicopathologic characteristics, treatment and survival were assessed in 39
      successive, newly diagnosed PGI-NHL patients (23 male and 16 female) treated at
      "Merkur" University Hospital. The aim of the study was to precisely evaluate
      their characteristics and compare them with the results reported from other
      similar studies. The most common site of PGI-NHL was stomach (n = 29, 74%),
      followed by small intestine (n = 5, 13%), and colon and rectosigmoid (n = 5,
      13%). According to the Ann Arbor classification, 34 (87%) patients had stage IE
      and IIE, and five patients (12%) stage IIIE and IVE. According to World Health
      Organization (WHO) classification, 29 (87%) patients had diffuse large B-cell
      lymphoma (DLCBL), two had mantle cell lymphoma, and seven (18%) had marginal zone
      B-cell lymphoma-mucosa associated tissue (MALT). Twenty-six (66%) patients
      underwent surgical resection followed by chemotherapy, ten (26%) were treated
      with chemotherapy alone, and three (8%) were treated surgically. Complete
      remission was achieved in 28 (72%) and partial remission in seven (18%) patients.
      Four (10%) patients had progressive disease. In our patients, the major
      prognostic factor for outcome was the stage of disease. Patients with localized
      lymphoma (stage IE and IIE) had a significantly longer overall survival: 85% at
      five years and 65% at ten years. Patients with extended disease (stage IIIE and
      IVE) had overall survival less than 33%. The prognostic power of erythrocyte
      sedimentation rate (ESR), total protein, serum albumin, LDH concentration and
      activity was analyzed. Of these parameters, only LDH had a statistically
      significant effect on overall survival. In conclusion, our patient group was
      comparable to other literature reports on PGI-NHL patients according to
      clinicopathologic characteristics. Disease stage and LDH were the only parameters
      that had a statistically significant effect patient survival.

PMID- 20698112
TI  - Evaluation of the HPV L1 capsid protein in prognosis of mild and moderate
      dysplasia of the cervix uteri.
AB  - Cervical intraepithelial neoplasia (CIN) can be detected in the cytologic smears
      years before invasive squamous cancer arises, but no reproducible morphologic
      criteria exist to predict behavior of cervical lesions. The possibility of
      predicting the clinical course of cervical lesions could be of high value in
      clinical practice and some women will spare of unnecessary treatment. HPV L1
      capsid protein represents about 90% of the total protein on the surface of the
      virus and can be detected in mild to moderate dysplasia and rarely in severe
      dysplasia. The purpose of the study was to evaluate the use of immunodetection of
      HPV L1 protein on archival Pap smears with findings of mild and moderate
      dysplasia in predicting its clinical course. Immunochemical analyses with L1
      antibody revealed positively stained nuclei of squamous epithelial cells in 56 of
      114 smears (49.1%). The staining results were correlated with follow-up smears or
      with histologic verification. Regression (negativisation of the Pap smear for 24
      months or longer) was noticed in 31 of 56 (55.4%) L1-positive cases and in 20 of
      58 (34.5%) L1-negative cases. Persistent disease occured in 13 (23.2%) L1
      positive cases and in 14 (24.1%) L1-negative cases. Progressive disease occured
      in 12 (21.4%) L1-positive cases and in 24 (41.4%) L1-negative cases. The
      difference in the clinical course between the L1-positive and L1-negative
      patients was statistically significant (p = 0.025). Also, the difference in the
      clinical course of the L1-negative staining in the under-30 and over-30 years age
      group was statistically significant (p = 0.04). For conclusion, our data confirm
      that immunostaining for HPV L1 capsid protein could offer prognostic information
      about mild and moderate intraepithelial cervical squamous lesions.

PMID- 20698113
TI  - Detection of t(14;18) by PCR of IgH/BCL2 fusion gene in follicular lymphoma from
      archived cytological smears.
AB  - According to WHO classification follicular lymphoma (FL) is a neoplasm composed
      of follicle centre (germinal centre) B-cells, which usually has at least a
      partially follicular pattern. Bone marrow (BM) infiltration by lymphoma occurs in
      40-70% of cases at the time of diagnosis. The characteristic chromosomal
      translocation of follicular lymphoma is t(14;18)(q32;q21) with transposition of
      BCL2 oncogene to the regulatory region of immunoglobulin heavy chain gene IgH.
      Aim of this study was to determine the frequency of PCR detection of IgH/BCL2 in
      DNA samples isolated from archival cytological slides of lymph node aspirates,
      bone marrow and/or peripheral blood (PB) obtained from patients with
      histologically confirmed follicular lymphoma using primers and protocol proposed
      by BIOMED-2 consortium. We also compared molecular with cytomorphological
      findings in bone marrow/peripheral blood and tested this method of detection of
      IgH/BCL2 molecular marker in monitoring minimal residual disease (MRD) in routine
      clinical setting. DNA was successfully isolated from all archival cytological
      slides obtained by fine needle aspiration of lymph nodes as well as from 75% of
      smears of bone marrow aspirates from 19 patients. Fusion oncogene was detected in
      10 of 19 patients (52%). For patients with PCR IgH/BCL2 positive lymph nodes,
      molecular test found BM infiltration in 5 cases (83%), while cytomorphology
      detected infiltration in three of eight cases (37%) available for comparison. May
      Grunwald-Giemsa stained cytological smears can be used for PCR-based ancillary
      methods and the rate of detection of IgH/BCL2 rearrangement is similar to results
      reported for paraffin-embedded tissues. For patients with detectable baseline
      molecular marker, PCR is a highly suitable method for detection of bone marrow
      involvement and monitoring MRD.

PMID- 20698114
TI  - Intraoperative imprint cytological assessment of the subareolar tissue of the
      nipple areola complex (NAC).
AB  - One of the criteria of selection for skin sparing mastectomy (SSM) with nipple
      areola complex (NAC) preservation is to exclude the neoplastic involvement of
      subareolar tissue (NAC base) in order to minimize the possibility of local
      recurrence. The most common way to assess the possible neoplastic involvement is
      intraoperative frozen section of the NAC base tissue. Because of its limitations,
      particularly the false negative results due to unsampling, we tried to use
      intraoperative imprint cytology for more thorough intraoperative assessment. The
      aim was to compare intraoperative imprint findings with the definitive histology
      of the NAC base, to evaluate diagnostic accuracy of this method and possibility
      to substitute frozen section for intraoperative assessment of NAC base. A
      prospective clinical study was conducted of 208 consecutive female patients who
      underwent open biopsy because of carcinoma. Intraoperative imprints were taken
      from the excised subareolar tissue which was then routinely processed for
      definitive histology. Imprint findings designated positive, negative, suspicious
      or atypia, were compared with definitive histological findings. Our results with
      7.5% false negative rate, 9.8% false positive rate, sensitivity of 50% and
      specificity of 87.58% argue that imprint cytology might not be sufficient as an
      exclusive method for the intraoperative assessment of the NAC base though it
      should be used routinely in conjunction with frozen section examination.

PMID- 20698115
TI  - A view at the future--a dynamical, protocol-based and computationally intensive
      approach in cardiovascular risk assessment.
AB  - Knowledge of cardiovascular risk factors is increasing. At the same time, risk
      estimation becomes more and more difficult. The need for a more comprehensive,
      but more individually based approach is evident. To achieve this aim, we propose
      a systems biology approach in cardiovascular risk assessment. This means that a
      large amount of health data, describing many aspects of the health-status of
      patients, is collected and computed and the results are compared with existing
      knowledge. Finally, a clinical model is created, which can be the first step in
      ongoing research protocol, aimed at assessing cardiovascular risk. By using this
      approach, all potentially relevant risk factors can be identified on a small
      sample. Moreover, risk groups can be more specifically defined, based on the
      "natural" clustering of data, according to their predictive load. We tested this
      possibility on an example of hyperhomocysteinemia which is a well-known complex
      cardiovascular risk factor.

PMID- 20698116
TI  - Vascular endothelial growth factor and intratumoral microvessel density as
      prognostic factors in endometrial cancer.
AB  - The aim of this research was to determine the VEGF A expression in tumor cells
      and the intratumoral microvessel density and their prognostic significance in the
      survival of the subjects. 87 subjects were monitored retrospectively for a period
      of 60 to 132 months. The subjects were treated at the Department of Obstetrics
      and Gynecology of Osijek University Hospital Center, Croatia. We analysed
      standard clinical, pathohistological and therapeutical prognostic factors,
      intratumoral microvessel density and expression of VEGF A. Five-year survival was
      calculated by the life chart method and presented graphically by Kaplan-Meier
      curves. Reaching conclusions on statistical hypotheses in this paper was done
      with a reliability level p < 0.05. Of the analyzed clinical prognostic factors,
      those which proved to be statistically significant and independent prognostic
      factors were age and clinical stage of the disease, and of pathohistologic ones
      it was the depth of myometrial invasion and VEGF expression. An elevated VEGF
      expression is associated with deep myometrial invasion, poorly differentiated
      tumors, histologic type and intratumoral microvessel density to a statistically
      significant degree. Elevated VEGF expression, age, FIGO stage and depth of
      myometrial invasion play a significant prognostic role in patients with
      endometrial cancer. VEGF receptors could be a target for adjuvant therapy in VEGF
      positive endometrial cancer.

PMID- 20698117
TI  - Cytogenetic follow-up in testicular seminoma patients exposed to adjuvant
      radiotherapy.
AB  - Early stage testicular seminoma is a radiosensitive tumor. Its incidence has
      significantly increased during the last decade especially in the young
      population. Although the therapy for testicular seminoma gives very satisfying
      results, the evaluation of genome damage caused by the therapy is of a great
      importance in order to recognize possible related health risks. The present study
      was performed on ten patients diagnosed with seminoma stage I; pT1/2N0M0S0,
      treated with adjuvant radiotherapy (a radiation dose of 25 Gy divided in 16
      fractions) after orchidectomy. To assess the possible existence of an increased
      baseline DNA/chromosome damage in patients we also selected the appropriate
      control group often healthy men. The levels of primary DNA/chromosome damage in
      peripheral blood lymphocytes, as well as the dynamics of their repair were
      studied using the alkaline comet assay, chromosome aberration and cytokinesis
      block micronucleus assay. Altogether four blood samples per patient were
      collected in the course of the therapy: before and after receiving the first dose
      of radiotherapy, in the middle of the radiotherapy cycle, and after the last dose
      of radiotherapy. Other two follow-up blood samples were collected six and twelve
      months after the cessation of therapy. As observed, the administration of the
      first radiation dose significantly increased the levels of DNA damage in almost
      all patients compared to their baseline values. Specific patterns of DNA damage
      were recorded in samples analyzed in the middle of radiotherapy and after
      receiving the last dose, indicating the possibility of an adaptive response in
      some patients. The levels of chromosomal aberrations and the incidence of
      micronuclei also increased in the course of therapy but gradually declined during
      the follow-up period. Our results confirmed the existence of post-irradiation
      damage in peripheral blood lymphocytes (and possibly in other non-target cells)
      of cancer patients which may represent a risk for the secondary cancer
      development. Considering that the majority of patients with testicular cancer are
      of a younger age, they represent a population deserving special attention. As
      cytogenetic screening may detect high-risk individuals, it might be useful in
      regular medical monitoring of seminoma patients after the successful therapy.

PMID- 20698118
TI  - Variations of body physique in Santhals: an Indian tribe.
AB  - In order to assess sex differences in body physique in Santhals, a cross
      sectional sample of 800 adult Santhals (400 males and 400 females) was collected
      from West Bengal (India) using multistage cluster random sampling. The present
      study aims to explore the body physique of Santhals of West Bengal, where both
      males and females do backbreaking labor work. This type of research is rare in
      tribal communities, especially in India. Anthropometric Somatotyping, the method
      forwarded by Heath and Carter, is followed in the present study, which is a
      technique of rating human body physique and composition through anthropometric
      measurements. The results suggest that the Santhal males and females are
      predominately Mesomorphic in their body physique. Mean somatotype of Santhal
      males and females are 1.98-4.81-3.98 and 3.16-5.43-3.17 respectively. Variation
      among Santhal females is more than males in terms of their body physique. Males
      in general are linear and muscular, whereas females are lean to fatty, but
      muscular.

PMID- 20698119
TI  - Empirical verification of the weighted system of criteria for the elite water
      polo players quality evaluation.
AB  - The aim of this research was to check the validity of the weighed system of
      criteria for evaluating the actual quality of water polo players proposed by
      Hraste, Dizdar and Trninic. The authors have determined the attributes of the
      measurement instrument for assessment of the overall performance efficiency of
      elite water polo players. Based on the determined descriptive indicators, on the
      coefficients of the relative importance of criteria, and on the degree of the
      objectivity level (interobservers' agreement) of the expert evaluations, it can
      be concluded that the measuring attributes (objectivity and sensitivity) for most
      of the criteria are in accordance with their relative importance coefficients for
      a particular position in the game. Consequently, a structure of relevant criteria
      is proposed for each play action position in the water polo game. The established
      instrument for evaluation the actual quality of the elite water polo players is a
      precondition to establish the professional system orientation, but it would also
      mean and a hypotheses for adequate design tactic model of play and a process of
      sports preparation. In succeeding steps of developing the system of criteria and
      its applicability, the latent structure of the criteria variables should be
      determined as well as overall importance of criteria with respect to the game of
      water polo.

PMID- 20698120
TI  - Increased demand for E-mail health consultation service: analysis of a Web
      survey.
AB  - The aim of the study was to explore characteristics of the users of the
      Interactive Service "Your Questions" that is based on E-mail health
      consultations. We wanted to find out what motivated users to use it, were they
      satisfied with it and what were its impacts on their health behavior. Therefore,
      we developed a Web survey and invited 2,747 users to take part in it. 919 (33.5%)
      of users responded. Results showed that the majority of respondents were women
      (79.1%) and that most hold at least a college degree (52.4%). The Service was
      mostly used for obtaining information about certain medical symptoms or medical
      conditions (50.1%), for a second opinion on a diagnosis (18.6%) and for more
      information about medical treatment (14.4%). In terms of Service features, it was
      used because of its convenience with regard to time (38.7%) and a sense of
      privacy (25.7%). Before posting a question to the Service, 93.2% of the
      respondents searched for health articles on the PLIVAzdravlje portal while 90% of
      them read the Questions and Answers database. Over half of them (61.8%) posted
      their question after they already visited their physicians on that particular
      issue. Nevertheless, 48% of them were encouraged to visit their physicians after
      they received the answer. The results show an important trend of increased demand
      for e-mail health consultation and the need for reliable medical information,
      with one thousand questions submitted to the Service in the observed period of 40
      days. If the source of medical information is reliable, as in case of our Service
      as well as other forms of e-mail health consultations, it can have positive
      impact on valuable physician-patient communication based on knowledge and mutual
      understanding.

PMID- 20698121
TI  - An active lifestyle explains sex differences in physical performance in children
      before puberty.
AB  - The aim of this study is to analyze differences according to sex in physical
      performance in children before puberty, as well as other health-related
      variables. Study population was 137 boys and 156 girls (9.99 +/- 0.79 years). We
      measured weight and height, physical performance using five field tests
      previously validated in children, habitual physical activity and diet quality. A
      multinomial logistic regression coefficient was established to calculate odd
      ratios (OR's) and 95% confidence intervals (CI's), to determine sex differences
      in performance, weight status, habitual physical activity and diet quality, and a
      t-test was calculated between active boys and active girls in order to establish
      differences in performance fitness test taking account habitual physical
      activity. Boys were more actives (OR 1.90, CI 1.03-3.49) and had better weight
      status than girls, while there was no difference in diet quality between sexes
      (OR 1.13, CI 0.67-1.89). In total sample, it was more probable to find greater
      physical fitness values in boys in all test performed. However, when both groups
      had a similar physical activity pattern, assessed physical fitness variables
      reached similar values and girls had better results only in flexibility.
      Sedentary patterns were more frequent in girls although there were no differences
      in diet quality between sexes. Girls tended to overweight more than boys did.
      Both sexes had a similar fitness performance before puberty for the same reported
      physical activity, except for flexibility, inferior in male subjects
      independently of their physical activity pattern.

PMID- 20698122
TI  - Geometric morphometric study and cluster analysis of late Byzantine and modern
      human crania.
AB  - Inter-population variation of cranial morphology, which plays an important role
      in human evolution studies and biological research, can be studied
      morphologically and metrically. Geometric morphometry compares body forms using
      specific landmarks determined by anatomical prominences. The aim of this study
      was to identify cranial shape differences between the crania of Byzantium period
      humans and modern humans. Variability in cranial shape was examined using the
      geometric morphometric technique based on landmark coordinates. Landmark
      coordinate data were collected from two-dimensional digital photogrammetry and
      were analyzed using generalized Procrustes analysis, hierarchical clustering and
      thin-plate spline analysis.

PMID- 20698123
TI  - Aerobiology of sweet chestnut (Castanea sativa Mill.) in north-west Croatia.
AB  - The aims of the study were to analyse characteristics of the Castanea airborne
      pollen and to compare aeropalynological data obtained from two sampling stations
      in north-west Croatia. The study was conducted in Zagreb and Samobor during the
      2003-2006 periods, using the seven-day volumetric samplers of the Hirst design.
      In both study areas, the seasons of chestnut pollination were similar and lasted
      from June to the end of July, which is comparable to other European cities. A
      general rule was noticed--the shorter the main pollen season, the higher the
      pollen peak concentration. Although the pollen season of Fagales pollen is
      prolonged to summer in the area of inland west-north Croatia due to the genus
      Castanea summer pollination, the number of days with pollen air concentration
      higher than 50 per m3 was low and was not likely to have any major effects in
      allergic individuals. Airborne pollen concentration of Castanea showed positive
      statistically significant correlation with air temperature and negative non
      significant correlation with precipitation. Because of the non-significant
      differences between the two stations, for a possible long-term forecast model for
      Fagales airborne pollen for this part of north-west Croatia, aerobiological data
      obtained from only one station are sufficient.

PMID- 20698124
TI  - Risk behavior of customers in centers for free voluntary HIV counselling and
      testing in two Croatian cities--Osijek and Zadar.
AB  - The primary goal of this research is to compare risks and occurrence of HIV
      infection in Osijek-Baranja and Zadar County. Several chosen socioeconomic
      factors controlled by sex and age were investigated including level of education,
      employment and marital status of the free-of charge voluntary counseling and
      testing center (VCT) customers in the towns of Osijek and Zadar and their risk
      behaviors for acquiring HIV. Bivariate analysis of the differences between the
      customers from Osijek and Zadar showed statistically significant differences in
      the following variables: gender, education, number of VCT clients who use
      intravenous drugs (IDU), promiscuous behavior, number of homosexual clients, mode
      of receiving information on the VCT services, marital and partnership status,
      having children, inclination towards homosexual and bisexual relations, the main
      reasons for not using condoms, injecting drugs (IDU) needle sharing and the
      occurrence of hepatitis C. The analysis showed that significantly more males were
      counseled and tested in the city of Osijek, significantly less hepatitis C
      positive persons and promiscuity among all behavioral risk factors more often. A
      higher number of the customers of the VCT in the city of Osjek were "in
      permanent" relationship. Strategic management of health and health care, methods
      of comparing regional and national standardized indicators can provide valuable
      information about setting the focus, choosing priorities and establishing a good
      economic policy at the micro level. This study clearly established the dimensions
      of problems in HIV/AIDS prevention onto which it should be influenced through
      regional and local measures and actions. The indexes measured indicate which
      special initiatives and programs should be focused and set up as priorities in
      particular regions. The determined differences point to the need for a regional
      approach to HIV/AIDS prevention in purpose of improving preventive activities
      according to most common risk behaviors. Even though Croatia is a relatively
      small country, it has many regional and local features which need to be taken
      into consideration when developing prevention programs and activities.

PMID- 20698125
TI  - Genetic contribution to variation in body configuration in Belgian nuclear
      families: a closer look at body lengths and circumferences.
AB  - The purpose of the current study was to evaluate the contribution of genetic
      factors on body configuration related phenotypes. The sample consisted of 119
      Belgian nuclear families including 231 males and 229 females. Factor analysis
      with varimax rotation was carried out to analyse 13 length and circumference
      measures and the resulting two synthetic traits (LF and CF; linear and
      circumference factors, respectively) were used as summary variables. Univariate
      quantitative genetic analysis indicated that variation in anthropometric as well
      as in synthetic traits was significantly dependent on additive genetic effects,
      with heritabilities ranging from 0.55 to 0.88. Narrow sense heritability
      estimates were higher for measurements principally characterizing skeletal mass
      than in variables that also involve soft-tissues. Sex, age and their interactions
      explained 11-67% of the total phenotypic variance. This report also examined the
      covariations between pairs of anthropometric and synthetic traits (length
      measurements and LF vs. height; circumference measures and CF vs. weight and BMI;
      LF vs. CF). Significant genetic correlations among all the studied traits (except
      for middle finger length vs. height) confirmed the influence of pleiotropy on
      genetic determination of these phenotypes. Bivariate analysis showed that
      pleiotropic effects had a great influence in determining body traits variation
      within body length measurements, as well as between body circumferences and
      weight or BMI. In relation to the two synthetic traits, even the variation of
      body lengths and circumferences was highly determined by genetic factors, shared
      genetic influences were unlikely to explain much of the observed variation
      between LF and CF. The results of the present study allow us to conclude that in
      this population body configuration related traits are subject to a strong genetic
      control and that shared genes also contribute to this genetic structure.

PMID- 20698126
TI  - Visual evoked potential can be used to detect a prediabetic form of diabetic
      retinopathy in patients with diabetes mellitus type I.
AB  - The aim of this study was to evaluate the usefulness of visual evoked potential
      (VEP) testing in detecting retinal ganglion cell damage in patients with Diabetes
      Mellitus type I (DMI). VEP arise before diabetic retinopathy signs become
      ophthalmoscopically detectable. VEP testing was performed in 45 patients divided
      into three groups; 15 children with recently discovered DMI, 15 children with
      long-lasting DMI, and 15 healthy children as the control group. A statistically
      significant difference in VEP P100 wave amplitudes (Z = 4.02, p < 0.001) and
      latencies (Z = -4.66, p < 0.001) was found between children with established DMI
      and those with recently discovered DMI. Amplitude values decrease progressively
      and latency values increase progressively in children with DMI as the years pass.
      Progressive increases in VEP latency values are a direct sign of retinal ganglion
      cell damage, which takes place even before the first ophthalmoscopically
      detectable signs of diabetic retinopathy arise. Therefore, VEP should be
      considered as a valid method for detecting prediabetic retinopathy, which could
      contribute greatly to the prevention of diabetic retinopathy complications.

PMID- 20698127
TI  - Transforaminal lumbar interbody fusion (TLIF) and unilateral transpedicular
      fixation.
AB  - TLIF (transforaminal lumbar interbody fusion) is a method of interbody fusion,
      which is alternative to other vertebral fusion wherein, with an approach through
      intervertebral foramen, through lateral segment of intervertebral space,
      complications occurring with other methods are reduced. Today, there are numerous
      versions of this method in terms of implants and transplants. At our Department
      patients with axial pain resistant to conservative treatment of minimum six
      months underwent TLIF method with unilateral transpendicular fixation with
      polyaxial screws, CAGE filled with autologous transplant obtained by lamina
      resection, and posteromedial contralateral fusion. 22 procedures were performed
      at 22 levels, 10 for relapsing hernia, and 12 for disc herniation combined with
      degenerative changes on the same level. Pain reduction was significant; according
      to VAS score, lumbar pain was reduced from preoperative 8.5 +/- 0.8 to 2.4 +/-
      0.85 (-72.63%) a year after, and leg pain was reduced significantly from
      preoperative 8.45 +/- 0.91 to 2.072 +/- 0.81 (71%) 12 months after surgery. The
      Wilcoxon paired test demonstrated a significant difference between preoperative
      VAS score and the value measured 12 months after surgery (n = 22, Z = 4.1, p <
      0.001) leg and back, respectively. In 15 (68.2%) patients fusion was evidenced on
      standard X-ray of lumbar spine, and in 4 patients, with aggravated clinical
      presentation, fusion in 2 patients and pseudoarthrosis in 2 patients were
      evidenced by CT. Total 17 patients (77.3%) showed signs of fusion. In our study
      we demonstrated that unilateral ipsilateral transpedicular fixation, with
      positioning of one CAGE filled with local autologous transplant represents a
      reliable and successful method of treatment of axial lumbar pain.

PMID- 20698128
TI  - Mitochondrial, Y-chromosomal and autosomal variation in Mbenzele Pygmies from the
      Central African Republic.
AB  - In this paper, we carry out a combined analysis of autosomal (ten microsatellites
      and an Alu insertion), mitochondrial (HVR-1 sequence, 360 nucleotides) and Y
      chromosomal (seven microsatellites) variation in the Mbenzele Pygmies from the
      Central African Republic. This study focuses on two important questions
      concerning the admixture and origin of African Pygmies. Ethnographic observations
      suggest a sex-biased gene flow between the Bantus and Pygmies, an issue which
      could be clarified through genetic analyses may shed light. A study of
      intrapopulational variation of mtDNA and Y-chromosome produces results in
      accordance with the hypothesized matrimonial behaviour. In fact, while shared
      mitochondrial haplotypes belonging to the L1c5 (or L1c1a1 clade) sub-haplogroup
      provides evidence of a Pygmy-to-Bantu female biased gene flow, a male biased gene
      flow from Bantu to Pygmies is supported by the distribution of the Y-chromosomes
      bearing M2 mutation. The second part of our study regards the question of the
      genetic relationships between Western and Eastern Pygmies. Our results favour the
      pre-Bantu hypothesis which suggests that the two Pygmy groups separated in
      ancient times (at least 18,000 years ago), whereas they do not support the recent
      divergence and differential admixture hypothesis which posits their separation as
      a consequence of the Bantu expansion (2,000-3,000 years ago).

PMID- 20698129
TI  - Diversity of Y-short tandem repeats in the representative sample of the
      population of Canton Sarajevo residents, Bosnia and Herzegovina.
AB  - In our previous population study, we have used twelve Y-chromosomal short tandem
      repeats loci incorporated in the PowerPlex Y System to determine Y-STR diversity
      in B&H human population. With intent to obtain additional verification of the
      previously obtained results as well as to establish specific reference for a
      local B&H population, we have decided to test DNA samples collected from 100
      unrelated healthy male Canton Sarajevo residents (from Sarajevo region) for the
      same twelve Y-linked short tandem repeats loci. Qiagen DNeasy Tissue Kit (Qiagen,
      GmbH, Hilden, Germany) was used for DNA extraction from buccal swabs and
      PowerPlex Y System (Promega Corp., Madison, WI) has been used to simultaneously
      amplify Y-STR loci by PCR. PowerPlex Y System includes 12 STR loci: DYS19,
      DYS385a, DYS385b, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS437,
      DYS438 and DYS439. The total PCR reaction volume was 5 microL. PCR amplifications
      were carried out in PE GeneAmp PCR System Thermal Cycler (ABI). Electrophoresis
      of the amplification products was preformed on an ABI PRISM 310 genetic analyzer
      (ABI, Foster City, CA) according to the manufacturer's recommendations. The raw
      data were compiled and analyzed using the accessory software: ABI PRISM Data
      Collection Software and Genemapper version 3.2. In addition, we have compared the
      obtained "Sarajevo" dataset with the data previously generated for the entire
      Bosnian and Herzegovinian population, as well as with the available data on
      geographically close (neighboring) European populations. The results of this
      study will be used as guidelines in additional improving of research into genetic
      relationship among recent local B&H populations, both isolated and open, which is
      a long-term project in our country.

PMID- 20698130
TI  - Use of wild and semi-wild edible plants in nutrition and survival of people in
      1430 days of siege of Sarajevo during the war in Bosnia and Herzegovina (1992
      1995).
AB  - This study is a systematic overview of data on use of wild and semi-wild edible
      plants in nutrition of people in 1430 days of the siege of Sarajevo during
      aggression on Bosnia and Herzegovina (1992-1995). The author of this study spent
      all that time in Sarajevo. In 1993, the author prepared a survival program for
      people that included usage of edible wild plants. In addition, he conducted a
      detailed survey, including special interviews, on 630 people of average age 37.4
      years (55% residential inhabitants, the rest were refuges), 310 males and the
      rest were females. According to survey, 91 species of mostly wild plants and
      three species of fungus were used: Kuchneromyces mutabilis, Armillariella mellea
      and Coprinus comatus. Wild vegetables included 49 species, spices 24, wild fruits
      16, and 2 species of bread-plants. They belong to 26 plants communities, and grew
      on 24 different habitats (urban surfaces, river coasts, low forest and scrubs,
      meadows and rocky grasslands). The 156 plant parts (leaves, young branches,
      fruit, flower, seed, root and rhizome) from 91 plant species were used.
      Vegetables were dominant category of use (soups, pottages, sauces) with 80 ways
      of preparation (30.53%), then salads 41 (15.65%), spices 39 (14.89%), different
      beverages 38 (14.50%), sweets 21 (8.02%), nutritive teas 15 (5.73%), and other
      preparations. In order to improve conventional food (war pasta, rice, lentils,
      old beans) people used spices made from different wild plants.

PMID- 20698131
TI  - Ischemic preconditioning decreases laparoscopy induced oxidative stress in the
      liver.
AB  - Experimental studies indicate that oxidative stress during and after laparoscopic
      surgery may cause liver ischemia-reperfusion injury. The aim of the study was to
      assess the effect of ischemic preconditioning against liver damage during
      pneumoperitoneum on oxidative stress. Twenty one New Zealand rabbits were divided
      into three groups of seven animals. Control group (C) rabbits received anesthesia
      for 60 min alone; 15 mm Hg intra-abdominal pressure with CO2 for 60 min was used
      in the pneumoperitoneum group animals (PNP); and 15-min insufflation and 10-min
      desuflation followed by 60-min pneumoperitoneum were used in the ischemic
      preconditioning group animals (IP). Venous blood samples were obtained at
      different time points to measure lipid hydroperoxide, glutathione reductase and
      total antioxidant status as indicators of increased oxidative stress. Aspartate
      transaminase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase
      (LDH) levels were evaluated as indicators of hepatocellular injury. The Kruskal
      Wallis and Mann-Whitney U tests were used on statistical analysis. Elevated intra
      abdominal pressure was found to produce significant increase in lipid
      hydroperoxide at the end of pneumoperitoneum and 30 min after desuflation in
      comparison with pre-insufflation period, and with both C and IP groups at the
      same time points. Total antioxidant status level decreased significantly in the
      PNP group at 24 h of desuflation. At 24h of desuflation, the AST, ALT and LDH
      levels were significantly increased in the PNP group in comparison with the
      levels measured before induction of anesthesia, and with the C and IP groups.
      Study results demonstrated that ischemic preconditioning prevented hepatocyte
      injury and oxidative stress during CO2 pneumoperitoneum.

PMID- 20698132
TI  - Diet quality in elderly nursing home residents evaluated by Diet Quality Index
      Revised (DQI-R).
AB  - The objective of this research was to evaluate diet quality in elderly nursing
      home residents and to point out the critical dietary components. The participants
      (277 females and 62 males) were recruited from all elderly nursing homes in
      Zagreb and each of elderly nursing homes was equally represented in this study.
      The age of subjects was ranging from 61 to 93 years; most of the females (53.4%)
      and males (53.2%) were between 70 and 80 years old. The dietary data from the
      multi pass 24-hour recall were used to compute the Diet Quality Index Revised
      (DQI-R). DQI-R is an instrument that provides a summary assessment of a diet's
      overall healthfulness and is based on ten different aspects, including
      recommendations for both nutrient and food types. Pearson correlation analysis
      was used to compare the total DQI-R score with dietetic parameters and t-test was
      calculated between mean values of all the components of DQI-R as well as for
      total DQI-R score for men and women. The mean DQI-R score for the 339 sample was
      62.1 +/- 11.7. The biggest number of participants satisfied recommendations about
      dietary cholesterol intake (88.5% of participants) and dietary moderation score
      (71.1% of participants) but nobody satisfied recommendation about dietary
      diversity score. Only 3.2% of subjects had an adequate calcium intake (6.5% of
      male participants and only 2.5% of female participants). Recommended servings of
      fruit intake were satisfied by 19.8% of population, 30.4% satisfied vegetables
      recommendations and 38.6% recommendations for grains. According to DQI-R, beside
      positive dietary habits regarding dietary moderation and dietary cholesterol
      intake the population of elderly nursing home residents in the capital of Croatia
      needs improvement in other dietary habits in order to enhance successful aging.

PMID- 20698133
TI  - Creation and typology definition of the museum on the Internet.
AB  - Through advancing new technology, perspective of museum institution and museum
      profession is changed. The content analysis and analyze of used terminology by
      online users will show us which term is the most used between frequently used
      terms such are: online, electronic, Web, Internet, digital, virtual and cyber
      museums. This scientific paper suggests that online users don't differ mentioned
      terms while they search for museums on Web. Using the appropriate 'prefix" in
      order to better describe the typology of a museum on the Web is the first step in
      designing the future of the museums and certainly encourages serious approach in
      to the study of the new museum "entities".

PMID- 20698134
TI  - Single incision laparoscopic cholecystectomy--a new advantage of gallbladder
      surgery.
AB  - In this study is demonstrated our experience in single incision laparoscopic
      cholecystectomy (SILS), compared to standard laparoscopic cholecystectomy. There
      were 48 single incision laparoscopic cholecystectomies (SILS) performed during
      one-year period (A group) and results have been compared with a group of 50
      patients who underwent standard laparoscopic cholecystectomy (B group). Outcome
      measures included operative time, need for conversion, complications, additional
      analgesia for pain control after procedure, hospital stay and cosmetic outcome.
      The mean operative time was 46 +/- 3.5 min in A group, and 43 +/- 4 min in B
      patients group. Early postoperative complications were not detected. The mean
      hospitalization period was 2 days in both groups. Our experience suggests that
      SILS cholecystectomy can be performed with outcome similar to standard
      laparoscopic surgery while affording better cosmesis.

PMID- 20698135
TI  - Role of zinc in chronic gastritis.
AB  - Oxidative stress occurs in inflammation of gastric mucosa. The role of zinc in
      modulating oxidative stress has recently been recognized. Zn deficiency results
      in an increased sensitivity to oxidative stress and have a higher risk of musoca
      damage in inflammation. The aim of this study was to determine wheather chronic
      inflammation affects on the concentration of Zn2+ ions in gastric mucosa of
      patients with chronic gastritis. Forthy-three patients with chronic gastitis were
      enrolled. Patients were endoscoped. Histology and scoring of gastritis was
      performed following the guidelines of the updated Sydney system. Endoscopic
      finding of mucosa were scored according to a Lanza scoring system. The diagnosis
      of Helicobacter pylori (H. pylori) infection, histopathologic changes, intensity
      of inflammation and zinc concentration were determined from biopsies of gastric
      mucosa. The atomic absorption spectrophotometer was used to determine tissue
      concentrations of zinc. Twenty of 43 patients with chronic gastritis were
      uninfected by H. pylori. There was no statistically significant difference in
      tissue concentrations of zinc between H. pylori-positive and H. pylori-negative
      patients. From those infected patients 53.3% had chronic active gastritis. There
      was no statistically significant difference in tissue concentrations of zinc
      between patients with chronic active gastritis and patients with chronic inactive
      gastritis (p = 0.966). Zn in antrum showed positive correlation with density of
      H. pylori in antrum (Spearman' rho = 0.481, p = 0.020), negative correlation with
      density of H. pylori in corpus (Spearman' rho = -0.492, p = 0.017) and with zinc
      in corpus (Spearman' rho = 0.631, p =0.001). Tissue concentration of zinc was not
      affected by chronic inflammation of gastric mucosa in patients with chronic
      gastritis.

PMID- 20698136
TI  - Fine needle aspiration cytology of minimal breast cancer in Istria County.
AB  - Breast cancer is the most frequent malignant tumour and leading cause of death in
      women aged 35 to 64 years in Istria County. The minimal invasive carcinoma and in
      situ carcinoma have a better prognosis so we try to find them during preventive
      exams. The aim of this study was to identify minimal breast cancers in fine
      needle aspiration biopsies of breast lesions made in Pula General Hospital
      between the years 2006 and 2008. There were 39 tumours with a maximal diameter of
      less than 10 mm in 1316 biopsies and 251 cytologically diagnosed breast cancers.
      In most cases, they were solitary, well differentiated neoplasms (48.7%). They
      were diagnosed in women aged 39 to 89 years and most frequently found in women
      aged 60 to 69 years. The most frequent histological type of operated minimal
      breast carcinomas was invasive ductal carcinoma. In that period, the minimal
      breast cancer percentage of all cytologically diagnosed breast cancers was 15.5%
      but in the first 6 months of 2009, the result was 48.7%.

PMID- 20698137
TI  - Metastases to rare locations as the initial manifestation of non-small cell lung
      cancer: two case reports.
AB  - Non-small cell lung cancer is the most common type of lung cancer (about 80% of
      all lung cancers). It grows and spreads more slowly than small cell lung cancer,
      but still, when the primary tumour treatment starts, about 60% of patients with
      cancer already have some kind of malignant cell spreading. Metastases to hand
      bones and skeletal muscles are very rare (metastatic hand lesions represent 0.1%
      of all osseous metastases while metastases to muscles represent from 0.8 to 16%
      incidence in autopsy series); in case of metastases in such sites it can be
      usually expected to find metastases disseminated all over the body. Fine needle
      aspiration cytology has an important role to give accurate diagnosis or at least
      diagnosis of suspicion and thus to set the guidelines to a clinician for the
      further specific and cost-effective treatment. We will show two cases where the
      metastases of non-small cell lung carcinoma were the first signs of the disease
      located in uncommon body parts: a man with the metastasis to distal phalanx of
      the right thumb and a woman with nodal metastasis to the right gluteal muscle and
      subcutaneous tissue near muscle which show us that we have to pay our attention
      to the potential development of such lesions even on rare locations and even when
      there are no other symptoms. In both cases, patients did not have any other
      symptoms related to the lung cancer.

PMID- 20698138
TI  - Cervix cancer screening in Croatia within the European Cervical Cancer Prevention
      Week.
AB  - Croatia still has opportunistic screening and the organized national screening
      has been planned. The European Cervical Cancer Prevention Week was held twice in
      Croatia, in January 2008 and 2009. Within the first one in 2008, information
      campaign "For All Women" via mass media was held, and women were invited to the
      organized free gynecological examination and Papanicolaou test (Pap test) in the
      University Department of Gynecology and Obstetrics, Zagreb University Hospital
      Center. Following invitation 481 women attended the testing; the median age was
      55 years. There were more women aged > or = 50 (n = 353), with the highest
      participation in the age group 55-59 years (n = 94). Some women came because of
      subjective symptoms (n = 10), but the majority of them came only for testing (n =
      471). According to history of previous cytological testing, 400 women have had >
      or = 1 negative findings, 71 women have had > or = 1 positive findings, 9 women
      attended Pap test for the first time, and 1 woman does not know about previous
      testing. Cervical cytology was abnormal in 35 women (7.28%), the median age was
      42 years with the highest proportion in the age group 30-34 years (n = 7); among
      all of them 21 women (60%) had no abnormal Pap test previously. The findings
      were: Atypical squamous cells of undetermined significance--ASC-US (n = 9), ASC
      cannot exclude high-grade squamous intraepithelial lesion--ASC-H (n = 1),
      cervical intraepithelial neoplasia--CIN 1 (n = 13), CIN 2 (n = 1), CIN 3 (n = 6),
      carcinoma planocellulare (n = 2), atypical glandular cells--AGC-favor reactive
      endocervical cells (n = 3). Among women aged < or = 49 there were 20.47% abnormal
      findings and among those aged > or = 50, 2.55%. According to 21 positive Pap
      tests previously, among women aged < or = 49 there were 30.71% while among those
      aged > or = 50 there were 9.07%. Within the European Cervical Cancer Prevention
      Week in 2009, employed women from one national company were invited by internal
      information to the same procedure. A smaller group of younger asymptomatic women
      came for testing (n = 53), median age 39 years. According to history of previous
      cytological testing, 50 women have had > or = 1 negative findings, 3 women have
      had > or = 1 positive findings. In this study, Pap test was positive in 3.77% (n
      = 2). National screening programme should be focused on the participation of all
      personally invited women, especially younger age groups and under-screened women.
      Well designed information campaign should be implemented in national screening
      programme.

PMID- 20698139
TI  - Aplastic crisis induced by human parvovirus B19 as an initial presentation of
      hereditary spherocytosis.
AB  - The association between aplastic crisis and human parvovirus (HPV) B19 infection
      has been described in patients with hereditary spherocytosis (HS). Most cases of
      aplastic crisis in patients with HS induced by HPV B19 have been reported in
      children and adolescents. In this paper, we describe an aplastic crisis induced
      by HPV B19 in the 34 year old female as an initial presentation of HS. Although
      other viral illnesses cause some decompensation in HS, the anemia is rarely as
      profound as seen in acute HPV B19 infections.

PMID- 20698140
TI  - Polyomavirus associated nephropathy after kidney and pancreas transplantation:
      case report.
AB  - Polyomavirus virus associated nephropathy (PVAN) is an important cause of graft
      failure in the renal transplant population. The prevalence of PVAN has increased
      from 1% to 10% in the past decade, leading to loss of transplanted organ in 30%
      to 80% of cases. In the absence of specific antiviral drugs, early detection of
      disease and modification/reduction of immunosuppressive regimen is currently the
      cornerstone of therapy. In the setting of multiorgan transplantation, like
      simultaneous pancreas and kidney transplantation (SPKT), diagnosis and therapy of
      PVAN can be even more challenging problem. We report a first described case of
      PVAN in patient after SPKT in Croatia. Patient is a 32 years old Caucasian male
      with type 1 diabetes mellitus and end stage renal failure, diagnosed for PVAN 6
      month after SPKT. Patient was treated with reduced immunosuppressive regimen. At
      32 month follow up, patient has preserved kidney and pancreas function with
      estimated glomerular filtration (eGFR) rate of 91 mL/min and no signs of PVAN on
      his 2 year protocol kidney biopsy.

PMID- 20698141
TI  - Double, ectopic blind-end ureter: a case report.
AB  - We report a case of a complete, ectopic blind-ending ureteral duplication in a 26
      year-old man who presented with the symptoms of an acute urinary tract infection
      for the first time. Since anamnestic data and clinical examination indicated a
      complicated urinary infection he was referred for further examination. On the
      left side, the imaging studies revealed a normal ureter draining the lower pole
      of the kidney and a blind-ending ureter with ectopia in the seminal vesicle. The
      patient recovered completely following surgical removal of the blind-ending
      ureter.

PMID- 20698142
TI  - Familial hemophagocytic lymphohistiocytosis in a 6-week-old male infant.
AB  - Familial hemophagocytic lymphohistiocytosis (FLH) is an autosomal recessively
      inherited multisystem disease. This defect in cellular cytotoxicity is a life
      threatening condition characterized by fever, rash, splenomegaly, cytopenias and
      neurologic manifestations. PRF1, UNC13D and STX11 gene defects underlie in about
      40-50% of primary cases. Chemoimmunotherapy followed by hematopoietic stem cell
      transplantation improved disease outcome. We report a case of a 6-week-old boy
      who presented with a fever, diffuse rash, disseminated intravascular coagulation,
      hypofibrinogenemia, hypertrigliceridemia, hepatosplenomegaly, leukocytosis with
      90% of lymphocytes, granulocytopenia, anemia, trombocytopenia, hyperferritinemia
      and pathological findings in cerebrospinal fluid. The patient had decreased
      frequency of NK cells and low NK cell activity in peripheral blood. Bone marrow
      aspiration analysis showed degenerative changes of histocyte cells, with
      preserved cytophages (lymphophages and erythrophages) consistent with
      hematophagocytic syndrome. Given that the molecular diagnosis of the known
      mutations in genes PRF1 and UNC13D showed a mutation in UNC13D, the diagnosis of
      familial hemophagocytic lymphohistiocytosis subtype 3 was established. HLH-2004
      chemotherapy protocol was performed and partial remission with residual central
      nervous system disease was achieved. Hematopoietic stem cell transplantation was
      successfully performed with an unrelated HLA-matched donor. Familiar HLH is
      generally a progressive and fatal disease. Early diagnosis with molecular genetic
      analysis and chemoimmunotherapy followed by hematopoietic stem-cell
      transplantation is the best approach.

PMID- 20698143
TI  - Rhabdomyosarcoma with bone marrow infiltration mimicking hematologic neoplasia.
AB  - Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children younger
      than 15 years. According to the World Health Organization, there are embryonal,
      alveolar and pleomorphic types of RMS. Most RMS patients present with a tumor
      mass in the head and neck region, urogenital tract or lower extremities. Unusual
      clinical presentation of the disease with massive bone marrow infiltration at the
      disease onset and mimicking hematologic neoplasm is rarely seen. A case is
      presented of a 14-year-old, previously healthy girl hospitalized for outpatiently
      detected leukocyte elevation. For the last two weeks, she had complained of
      fatigue, myalgia and frequent bruising. On admission, clinical examination
      revealed numerous petechiae and hematomas, enlarged left inguinal lymph node and
      palpable spleen 2 cm below left costal arch. Laboratory findings showed
      leukocytosis, anemia and thrombocytopenia. Bone marrow fine needle aspiration
      (FNA) produced a hypercellular bone marrow sample with suppression of all three
      hemocytopoiesis lines and bone marrow infiltration with numerous undifferentiated
      tumor cells. Considering the morphological, cytochemical and phenotypic
      characteristics, the cytologic diagnosis was: bone marrow infiltration with RMS
      cells. Abdominal computerized tomography revealed a primary tumor occupying the
      entire retropeoritoneal space. Tumor biopsy confirmed alveolar subtype of RMS. In
      conclusion, in cases of bone marrow infiltration with primitive, immature cells,
      RMS should be considered as differential diagnostic possibility. Adjuvant
      technologies (cytochemistry, immunocytochemistry, cytogenetic analysis, flow
      cytometry, and molecular analysis) can be very helpful in diagnostic work-up, and
      may lead to definitive diagnosis in some cases.

PMID- 20698144
TI  - Myeloid sarcoma involving the breast.
AB  - Myeloid sarcoma is a tumor mass with extramedullary growth pattern, composed of
      myeloblasts or immature myeloid cells. The development of myeloid sarcoma may
      precede or concur with acute or chronic myeloid leukemia (AML or CML) or other
      myeloproliferative diseases or myelodysplastic syndromes (MDS). Isolated myeloid
      sarcoma of the breast is very rare. A case is presented of a 25-year-old,
      previously healthy woman that presented to our department for a palpable node, 5
      x 2 cm in size, in the upper medial quadrant of her left breast. Fine needle
      aspiration (FNA) produced a sample consisting of medium sized blasts. Additional
      work-up revealed anemia, thrombocytopenia and leukocytosis, along with atypical
      blasts detected in peripheral blood and bone marrow smear. Based on the
      morphology, cytochemical characteristics and immature cell immunophenotype, it
      was considered a case of acute myeloid leukemia without maturation. In spite of
      intensive chemotherapy, the patient died within a year of diagnosis. In cases of
      isolated breast myeloid sarcoma, the diagnosis can be missed if the possibility
      of myeloid sarcoma is not remembered on differential diagnosis of a breast
      neoplasm.

PMID- 20698145
TI  - A case report of breast angiosarcoma.
AB  - Angiosarcoma is a rare disease of the breast with the reported incidence of only
      0.04% of all breast malignancies. The etiology of angiosarcoma remains unknown.
      It occurs post-mastectomy, in association with chronic lymphedema (Stewart-Treves
      syndrome), or after radiotherapy. We present a patient with angiosarcoma which
      developed 12 years of the diagnosis of breast carcinoma and 8 years of the
      operative procedure and radiotherapy for disease recurrence. A small angiomatous
      lesion of a few mm in size, cytologically suspect of vascular tumor (hemangioma
      or hemangiopericytoma) and histopathologically verified to be an atypical
      vascular lesion, was detected two years before breast enlargement and cytologic
      and histologic diagnosis of angiosarcoma. The patient died 15 months of the
      diagnosis of angiosarcoma, after two tumor recurrences and intrathoracic cavity
      invasion.

PMID- 20698146
TI  - Vulvar Paget's disease--a case report.
AB  - Vulvar Morbus Paget (MP) represents a rare intraepithelial adenocarcinoma. It
      accounts for less than 1% of all vulvar neoplasia and usually appears in
      postmenopausal women. Histologically it is analogous to Paget's disease of the
      breast. The most common clinical symptom is pruritus. The lesion appears as an
      erythematous or as an eczematous lesion with islands of hyperkeratosis.
      Occasionally, single anaplastic Paget's cells can be found on the vulvar smears
      which make cytological diagnosis of the disease possible. However, the disease
      can be diagnosed only by biopsy. We present a case of 49-year old woman with
      vulvar symptoms of pruritus, who had liver and kidney transplantation two years
      ago. During the standard gynecological examination the vulvar smear was taken for
      cytological evaluation. The smear was scanty, with inflammatory background,
      overloaded with squamae. There were two types of cells: dysplastic squamous cells
      from lower layer of the epithelium and the single, anaplastic cells with a high
      nuclear:cytoplasmic ratio who possessed eccentric, large nucleus. Nucleoli were
      rare. Cytoplasm varied from pale and delicate to densely basophilic. Accordingly,
      cytological diagnosis vulvar intraepithelial neoplasia (VIN III) with
      differential diagnosis of vulvar Paget's disease was made. The pathological
      verification supported the diagnosis of MP and an immunohistochemistry panel
      confirmed type III of Paget's disease and an evaluation of bladder was suggested.

PMID- 20698147
TI  - Simultaneous occurrence of chronic lymphocytic and chronic myeloid leukemia.
AB  - The coexistence of chronic lymphocytic (CLL) and chronic myeloid leukemia (CML)
      in the same patient has only been reported occasionally. Most of these cases
      represent the patients who developed CLL during the course of CML. Reviewing the
      literature, only a few cases of simultaneous occurrence of CLL and CML were
      found. Here we represent a previously healthy 50-year old man in whom the
      diagnosis of CLL and CML was established by FNAB of the bone marrow. The
      diagnosis was then confirmed by histopathology, immunophenotypization of the
      peripheral blood and by a cytogenetic study of the bone marrow. Four years after
      the diagnosis the patient is well, with leucocytosis of 40 x 10(9)/L, and
      lymphocytosis of 93%.

PMID- 20698148
TI  - Klinefelter syndrome and acute basophilic leukaemia--case report.
AB  - Patients with 47, XXY karyotype (Klinefelter syndrome) appear to have increased
      risk of developing cancer, especially male breast cancer, germ cell tumours and
      non Hodgkin lymphomas, but rarely acute myeloid leukaemia. We report a patient
      with acute basophilic leukaemia with 47, XXY karyotype in both the tumour and
      constitutional cells. Acute basophilic leukaemia is very rare disease comprising
      less than 1% of all acute myeloid leukaemias. Morphological characteristic of
      leukaemic blast cells is moderately basophilic cytoplasm containing a variable
      number of coarse basophilic granules. The most characteristic cytochemical
      reaction is metachromatic positivity with toluidine blue. Blast are
      myeloperoxidase negative. Also leukemic blasts express myeloid and monocyte
      markers. There is no consistent chromosomal abnormality identified in this
      leukaemia. This is the first reported case of acute basophilic leukaemia in
      patient with Klinefelter syndrome. In this article the medical history of the
      patient is given and the possible connection between Klinefelter syndrome and
      acute myeloid leukaemia is discussed.

PMID- 20698149
TI  - Septic arthritis due to Streptococcus sanguis.
AB  - Septic arthritis may represent a direct invasion of joint space by various
      microorganisms, including bacteria, viruses and fungi. Although any infectious
      agent may cause bacterial arthritis, bacterial pathogens are the most significant
      because of their rapidly destructive nature. We present a case of septic
      arthritis in a 56-year old male patient due to Streptococcus viridans which is
      member of the viridans group streptococci. Patient was admitted to Our Hospital
      presented as fever of unknown origin, losing more than 30 kg of body weight
      during couple of months, and anemia of chronic disease as paraneoplastic process.
      He had long history of arterial hypertension and stroke. There was swelling and
      pain of the right sternoclavicular joint and precordial systolic murmur in
      physical status. A large diagnostic panel has been made, computerized tomography
      (CT) of right sternoclavicular joint showed widening of periarticular soft tissue
      and loss of clavicular corticalis. Cytologic analysis of synovial fluid showed
      more than 90% of polymorphonuclear leukocytes. There were no crystals on
      microscopic examination and Gram stain of fluid was negative. Blood cultures were
      positive for S. sanguis and there was a consideration about possible periodontal
      disease. Stomatologic examination verified periapical ostitis and extraction of
      potential cause of infection has been done. Therapy with benzilpenicilline was
      followed by the gradual improvement of clinical and laboratory parameters.
      Although viridans group streptococci and Streptococcus sanguis in particular are
      rare causes of septic arthritis in native joints, they should be considered in
      the differential diagnosis of periodontal disease.

PMID- 20698150
TI  - Fine needle aspiration cytology of adrenocortical carcinoma--case report.
AB  - A 49-year-old woman presented for hirsutism, deep voice and hypertension.
      Ultrasonography (US) revealed a solitary tumor mass, eight cm in size, of the
      right adrenal gland. Laboratory tests showed it to be a hormonally active,
      androgen secreting tumor (elevated testosterone level), which was consistent with
      the clinical picture of the disease. After histopathological analysis tumor was
      signed out as adrenocortical carcinoma, a low risk carcinoma according to Weiss'
      classification. One year later on regular follow up, US revealed a suspicious
      growth measuring 65 x 43 mm in the projection of the lower pole of the right
      kidney. The finding was verified by computerized tomography and the patient was
      reoperated on. Exploration revealed secondary growth in the region of greater
      omentum, without infiltration of adjacent organs. Histopathologic analysis
      confirmed metastatic ACC. 8 months after the second operation and after 6
      chemotherapy cycles according to EAP protocol, control CT showed enlarged para
      aortic lymph nodes and a node along the upper pole of the right kidney. Cytologic
      puncture was performed. Cytologic opinion was recidive of primary malignant
      disease. ACC is a rare malignant epithelial tumor of adrenal cortical cells, with
      high malignant potential. Morphologically (histopathology and cytology),
      differential diagnosis includes adenoma on the one hand, and renal cell carcinoma
      (RCC) and hepatocellular carcinoma (HCC) on the other hand. A combined evaluation
      of clinical features, size or weight, microscopic appearance, immunohistochemical
      and molecular genetic data is necessary to ensure a correct diagnosis. The
      purpose of this case report is to present clinical and cytomorphologic features
      of our case of adrenocortical carcinoma which is very rare in cytology practice.

PMID- 20698151
TI  - Fine-needle aspiration cytology of apocrine hidradenoma.
AB  - An apocrine hidradenoma is a benign adnexal neoplasm, usually covered by intact
      skin, but may show superficial ulceration and serous discharge. This feature is
      raising the possibility of malignancy as it was in our case of macroscopically
      suspicious tumour. We described cytomorphologic features of cutaneous nodule that
      might be a lead to the cytologic diagnosis of hidradenoma, but primary or
      secondary malignant tumour has been ruled out first.

PMID- 20698152
TI  - T lymphoblastic leukaemia with an unusual Burkitt lymphoma morphology--a case
      report.
AB  - Precursor T-cell acute lymphoblastic leukaemia (T-ALL)/lymphoma (T-LBL) is a
      neoplasm with cytological features that include blast cells of medium size, high
      nuclear cytoplasmic ratio and inconspicuous nucleoli, which are usually TdT
      (Terminal Deoxynucleotidyl Transferase) positive and variably express T-cell
      markers. We report a case of T-ALL with atypical cytological presentation which
      showed lymphoblasts with homogenous nuclear pattern, larger amounts of cytoplasm
      with vacuoles and prominent nucleoli. A 56-year-old male was hospitalized due to
      high fever and kidney infection. Further examination confirmed anemia,
      thrombocytopenia, normal level of white blood cells and high level of lactat
      dehydrogenase (LDH). Bone marrow aspiration revealed 87% and peripheral blood 41%
      of lymphoblasts with cytoplasmic vacuoles which suggested Burkitt lymphoma (BL)
      morphology. Patient's karyotype showed no chromosomal aberations. Identification
      of immunophenotype discovered cells which were CD2 and CD3 positive and CD20
      negative with focal acid phosphatase activity in 67% of blasts. This excluded
      Burkitt lymphoma and led to diagnosis of T-ALL. The patient was submitted to two
      cycles of chemotherapy, autologous stem cell transplantation, and intrathecal
      chemotherapy, but he died after 10 months because of disease complications (lung
      aspergillosis and pleural effusion). Our case report showed how morphology alone
      can be misleading and sometimes is not enough in diagnosing ALL. Beside
      morphologic criteria, setting correct diagnosis depends on identification of
      immunophenotype by flow cytometry and cytogenetic-molecular abnormalities.
      Further improvements in the molecular definition of ALL subtypes, development of
      new and targeted drugs will improve patient's outcome and prognosis.

PMID- 20698153
TI  - Subcutaneous panniculitis-like T-cell lymphoma in a 19 month-old boy: a case
      report.
AB  - Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare type of T-cell
      lymphoma of CD3+CD8+ phenotype characterized by deep-seated skin nodules or
      plaques mimicking panniculitis, a result of neoplastic lymphocytes infiltrating
      the subcutaneous fatty tissue. We present a case of a 19-month year old boy with
      SPTCL diagnosed and successfully treated in our institution. Disease first
      presented with symptoms of high fever and painful erythematous nodule located
      below the umbilicus. Later on the infiltrates appeared on the face, legs, arms
      and the back of the body. As the most decisive in obtaining the diagnosis, skin
      biopsy showed atypical, small to medium-sized lymphatic cells infiltrating the
      deeper dermal layers as well as the subcutaneous adipous tissue surrounding the
      adipocytes. Immunohystochemical analysis showed neoplastic lymphocytes positive
      for CD2, CD3, CD5, CD7, CD8, Tia-1, granzyme B and perforine, and negative for
      CD20, CD34, TDT and CD56. No infiltration of blood vessels or epidermis was
      evident. Specific T-cell lymphomas protocol (EURO-LB 02) was then initiated which
      resulted with rapid regression of all general and local symptoms. The treatment
      was completed according to schedule and the child is now, 24 months after the
      initiation of the treatment, in complete remission.

PMID- 20698154
TI  - Pelvic ganglioneuroma--case report.
AB  - Ganglioneuromas are rare, benign, slow-growing tumors originating from
      sympathetic ganglion cells. The most common locations are the posterior
      mediastinum and retroperitoneum. Pelvic ganglioneuroma is very rare. The case of
      a 12-year-old girl with presacral ganglioneuroma is reported. The importance of
      considering a confident preoperative diagnosis by fine-needle aspiration biopsy
      is stressed.

PMID- 20698155
TI  - Fine needle aspiration cytology of chondroid syringoma.
AB  - Chondroid syringoma (CS) is a rare, benign, appendageal tumor with diagnostic
      feature of myxochondroid stroma supporting eccrine and apocrine epithelial
      structures. The usual presentation is a painless, slowly growing mass, typically
      located in the head and neck region. It usually affects middle-aged and older
      male patients. Because of its unremarkable clinical presentation it is often
      overlooked. It should be included in the differential diagnosis of cutaneous head
      and neck tumors, especially in middle-aged men. Optimal treatment of CS is total
      surgical excision. We present a 63 year-old man with a small nodule on the neck
      with 5 years of duration. The diagnosis was made initially on fine needle
      aspiration cytology that was performed by ultrasound guidance and confirmed
      subsequently by histology. FNA cytology may be very useful to determine diagnosis
      before excision.

PMID- 20698157
TI  - Dual kidney transplantation: case report.
AB  - Chronic shortage of kidney transplants worldwide has led to the use of organs
      from so called marginal or borderline donors, now termed "expanded-criteria
      donors". There has been an emerging practice of dual kidney transplantation (DKT)
      to compensate for sub optimal nephron mass of such kidneys. We performed DKT in
      "Merkur" University Hospital in August 2005. The donor was a 72-year old female
      with a history of long-term hypertension, aneurysm of the posterior cerebral
      artery, cerebrovascular insult (CVI), and with normal creatinine values and
      kidney function at the time of explantation. Initial biopsy of donor kidneys
      revealed acute tubular damage, with connective changes in 22% and 11% of
      glomeruli in the left and the right kidney, respectively. The recipient was a 60
      year old male diagnosed with the IgA nephropathy on the last biopsy in 1999, and
      on dialysis since November 2003. Postoperative course was uneventful without any
      surgical complications. A triple immunosuppressive protocol was used. On follow
      up ultrasonography 4 years posttransplantation both kidneys appeared of normal
      size and parenchymal pattern and with no signs of dilatation of the canal system,
      and color Doppler examination demonstrated normal flow in both kidneys. In
      conclusion, the use of DKT ie. donors by the expanded-criteria will continue to
      increase, and further studies of the results will, with no doubt, support this
      method.

PMID- 20698156
TI  - Fine needle aspiration cytology of metastatic Merkel cell carcinoma.
AB  - Merkel cell carcinoma (MCC) is uncommon cutaneous malignant neuroendocrine tumour
      of the elderly people with rapidly growing skin nodules found frequently on sun
      exposed areas of the body. MCC is often an aggressive tumour with high tendency
      for local recurrence, lymph node involvement and distant metastases. This paper
      reports a case of metastatic MCC diagnosed by fine needle aspiration cytology
      (FNAC), flow cytometric deoxiribonucleated acid (DNA) analysis, pathohistology
      and electron microscopy. The cytological features in aspirate (stained with
      Papenheim and Papanicolaou staining) included increased cellularity, discohesive
      groups of small-to-medium size malignant cells with uniform, round-to-oval nuclei
      with moulding effect, fine chromatin, multiple micronucleoli and scanty
      cytoplasm. DNA flow cytometric analysis of the aspirate showed unexpected results
      for clinically aggressive behaviour of this tumour (the patient died after 21
      months), and revealed that tumour contained diploid peak with DNA index of 1.1.
      The proliferation was high with elevated S-phase fraction (21%). The cytological
      diagnosis of possible metastatic MCC was confirmed by histological one as well as
      by electron microscopy presented the pathognomonic features for this tumour:
      dense-core neurosecretory granules with diameter of 100-250 nm surrounded by
      whorls of intermediate filaments. MCC provides an enormous challenge for the
      morphologist because of a wide range of differential diagnosis and for the
      clinician because this tumour has a highly malignant potential for local
      recurrence, nodal and distant spread and very often is combined with other
      tumours. Therefore it is important to perform FNAC of different lesions in the
      same patient because it can distinguish MCC from the other tumours.

PMID- 20698158
TI  - Synchronous bilateral breast carcinoma with two different morphology subtypes: a
      case report.
AB  - We report a case of synchronous bilateral breast cancer with ductal and medullary
      carcinoma. A 60-year-old woman presented with lesion in both breasts which were
      mammographically found two years ago. Ultrasonography proved two suspected masses
      in breasts. Fine needle cytology was performed and confirmed bilateral carcinoma
      but with different cytological findings. The cytological feature of the left
      breast suggested ductal carcinoma and of the right breast raised possibility of a
      medullary carcinoma. Patient underwent bilateral quadrectomy with evacuation of
      axillary lymph nodes. Histological examination showed bilateral carcinoma with
      two different histological features: ductal in the left and medullary carcinoma
      in the right breast.

PMID- 20698159
TI  - Apoptosis of leukemic cells: a case report.
AB  - Transformation of leukemic cells is associated with delay in maturation and in
      apoptosis, and to altered responsiveness to growth factors. However, some studies
      have revealed that Fas (CD95/APO1) which mediates apoptotic signal and decrease
      of anti-apoptotic Bcl-2 are frequently observed in acute myeloid leukemia (AML)
      M4/M5 leukemic cells. The aim of the study was to compare cytomorphology and
      cytochemistry of bone marrow (BM) apoptotic leukemic cells to preserved
      peripheral blood (PB) leukemic cells in our patient, a 76-year-old man with AML
      M5b treated at Zagreb University Hospital Center. BM and PB of the AL patient
      were analyzed after Pappenheim and cytochemical stainings, and leukemic cells
      were classified according to FAB and WHO classification. Analysis of PB revealed
      leukocytosis and 80-90% monocytic cells (46% monoblasts, 29% promonocytes and 11%
      monocytes). Only a few preserved monoblasts and promonocytes were found in BM,
      together with numerous morphologically altered cells with characteristic
      chromatin condensation and pyknosis of nucleus, as well as nuclear fragmentation
      and formation of apoptotic bodies. Thus, cytomorphology of PB leukemic cells
      pointed to proliferation of immature monocytic cells, and cytomorphology of BM to
      cell apoptosis. Cytochemistry of PB monocytic cells and BM apoptotic cells
      confirmed monocytic cell lineage because esterase was strongly positive in almost
      all BM apoptotic leukemic cells and PB leukemic cells, and esterase was
      completely inhibited with sodium fluoride. On the basis of these findings, AML
      M5b was diagnosed in our patient. There are many possible explanations for our
      observation of BM leukemic cell apoptosis in a patient with AML-M5. The most
      reliable one is that apoptosis was induced ex vivo after BM aspiration in course
      of the air drying of BM specimen before staining. Mass BM leukemic cell apoptosis
      that was recorded in contrast to numerous preserved leukemic cells in PK could be
      probably connected to unfavorable ratio of relatively low concentration of
      cytokines in relation to high leukemic cell number in BM aspirated cytologic
      specimen.

PMID- 20698160
TI  - Necrotising sarcoid granulomatosis of the spinal cord: case report.
AB  - We report a patient who presented with leg weakness and cervical lymphadenopathy.
      Thoracical magnetic resonance imaging showed an inhomogenously increased signal
      in the thickened portion of the cord. Multilevel laminectomy and spinal cord
      biopsy revealed granulomatous infiltrations with necrosis. Review of the
      histopathological finding established the diagnosis of necrotising sarcoid
      granulomatosis (NSG) of the spinal medulla, cytological FNA diagnosis of the neck
      lymph node was granulomatous inflammation with necrosis, but histopathological
      analysis of the same neck lymph node disclosed granulomatous inflammation without
      necrosis. On further radiographic chest evaluation mediastinal lymphadenopathy
      was found. Immunophenotyping of lymphocytes in bronchoalveolar lavage fluid
      (BALF) was indicative of sarcoidosis. After the administration of corticosteroid
      therapy the patient's clinical condition improved, and laryngeal and mediastinal
      lymph nodes subsided with minor changes remaining in the spinal medulla, which,
      based upon MR assessment, were considered to be irreversible. To our knowledge,
      this is the first described case with finding of granulomatous inflammation with
      and without vasculitis in various organs, consistent with the Churg's study who
      believes NSG to be a histological variant of sarcoidosis.

PMID- 20698161
TI  - Rectal metastasis from lobular carcinoma of the breast: a case report.
AB  - Rectal metastases from breast carcinomas are very rare. They often occur in
      lobular invasive breast carcinoma (ILC), usually after a long disease-free
      period. It is important to be aware of these unusual metastatic patterns of ILC
      of the breast because of the possibility of systemic therapy. We present a case
      of 83-year old woman with rectal metastesis from ILC seven years after surgery of
      primary tumor.

PMID- 20698162
TI  - Trauma related fat embolism syndrome in forensic practice.
AB  - The fat embolism syndrome (FES) in forensic practice is observed usually in cases
      of polytrauma related deaths. FES is rare, but serious complication after trauma.
      The most cases of post traumatic fat embolism are not fatal and it's very likely
      that many cases of mild fat embolism are overlooked. We describe a case of fat
      embolism syndrome in a young man after high energy injury. Upon concrete ceiling
      fell on his shoulders he had open fractures of both tibias and massive haematoma
      of the left hip joint. Transport immobilization of both legs was performed with
      admitting of analgesia during transportation to the hospital. Immediately after
      admission to hospital he underwent surgery. Several hours after osteosynthesis of
      both tibias, in ICU patient became hemodinamically and respiratory unstable. He
      developed global cyanosis and metabolic acidosis with significant decrease of
      oxygen pressure in the blood. Control chest radiograph showed typical "snow
      storm" like pulmonary infiltrations. Deep bradicardy occurred followed by
      cardiopulmonary arrest. CPR was unsuccessful and the patient suddenly died within
      12 hours from the incident. Histologic confirmation of fatty droplets the most
      commonly observed in the lung capillaries, brain capillaries or disseminated
      throughout the body remains diagnostic standard. We present one case of FES to
      emphasize the arising need of a quantitative analysis of both the size and
      localization of the fat emboli in order to grade the severity of FES and its
      relative contribution in pathophysiology of death. The postmortem diagnosis of
      fat embolism syndrome (FES), traditionally based on the histological
      demonstration of fat globules seems not to be enough, nowadays. A quantitative
      analysis of both the size and localization of the fat emboli has been discussed
      as reliable method of grading the pulmonary fat embolism in order to determine
      its relative functional contribution in death pathogenesis.

PMID- 20698163
TI  - Bilateral laryngoceles in association with squamos cell carcinoma: a case report
      and literature review.
AB  - Coexistence of laryngoceles and laryngeal carcinoma is still being debated, and
      there are several suggested theories about the pathophysiological relationship
      between these two entities. We present the case of a 66-year-old male patient
      with bilateral laryngomucoceles and laryngeal squamos cell carcinoma. A
      systematic hystological examination of whole organ sections showed that the
      submucosal spreading of cancer around the saccular necks on both sides caused
      stenosis which probably created a one-way valve mechanism allowing air to enter
      the saccule but not to exit. Progression of the tumor completely obstructed the
      laryngeal opening, leading to glandular secretion stagnation and formation of
      laryngomucoceles.

PMID- 20698164
TI  - Advances in cervical cancer control and future perspectives.
AB  - The knowledge that the persistent infection with high-risk (HR) human
      papillomavirus (HPV) is the etiological factor in the development of cervical
      cancer has led to the development of the HPV DNA detection methods as well as the
      prophylactic vaccine against the most common HR-HPV types, HPV 16 and 18. Despite
      HPV vaccination, cervical cancer screening will remain the main preventive
      measure for both vaccinated and non-vaccinated women, but the nature of screening
      and management of women with cervical disease is being adapted to the new
      technologies. Although, HPV DNA detection is more sensitive that cytology, its
      specificity is lower, since most HPV infections are transient. Therefore, other
      methods are considered to improve the management of women with cervical disease.
      Typing of HPV DNA and viral load measurements are still used for research
      purposes only. Detection of viral oncogene E6/E7 transcripts, which is the marker
      of the productive infection, is a promising tool for follow-up of HPV DNA
      positive women. The detection of p16INK4a over-expression, as an indirect test of
      E6/E7 expression, is used for confirmation of cervical neoplasia. Despite the
      lack of standardization, the detection of p16INK4a is useful in clinical
      settings, however its reproducibility in the management of low-grade and
      borderline cases is low. Future perspectives include the determination of the
      methylation status of several cellular genes that could predict the progression
      of the disease.

PMID- 20698166
TI  - Fine needle aspiration cytology of the pancreas: a guide to the diagnostic
      approach.
AB  - Fine needle aspiration (FNA) cytology, together with imaging, has become a
      primary diagnostic modality for investigation of pancreatic mass lesions, both
      cystic and solid. Advances in imaging techniques have enhanced our ability to
      recognize and delineate pancreatic masses and to detect them earlier as smaller
      mass lesions. However, definitive management often cannot be based on clinical
      and radiological features alone. Despite the advances in the imaging techniques,
      management options for patients are limited and a malignant diagnosis of solid
      lesions still carries a high mortality rate. The importance of a cytopathologist
      in preoperative diagnosis, as a member of the multidisciplinary team, is
      exemplified in the management of patients with neoplastic cysts. This is based on
      the pre-operative distinction of non-mucinous and mucinous cysts in general, and
      benign and malignant cysts in particular. A cytological diagnosis can be obtained
      with minimally invasive techniques that utilize CT US or EUS. Endoscopic
      Ultrasound guided FNA (EUS FNA) is evolving as the diagnostic method of choice
      due to its ability to more accurately stage the patient during a single procedure
      using EUS.

PMID- 20698165
TI  - Clinical cytology and primary health care of children and adults.
AB  - Clinical cytology is a diagnostic branch of medicine, best known by the Papa test
      in gynaecology. But, cytology can be applied in almost all fields of clinical
      medicine. Its advantages--high accuracy, simplicity, with little or no
      aggressiveness and low cost--are not used as widely as they could be. Medical
      practice, as well as medical research, and also medical education, are nowadays
      often directed at profitable use and not at the real benefit of the patient.
      Primary practitioners do not have enough chance to get acquainted with clinical
      cytology as a whole although they need true information, based on the cost
      effectiveness and patient-benefit. A panel discussion on this subject was
      organised at the 4th Croatian Congress of Clinical Cytology, in Split, October 11
      14, 2009 by the Croatian Society for Clinical Cytology-Croatian Medical
      Association, to inform primary practitioners about the possibilities of
      cytodiagnostics in the health care of children and adults. Indications for
      cytodiagnostics in infectious diseases (T. Jeren and A. Vince), haematology (I.
      Kardum-Skelin), pulmonology (S. Smojver-Jezek), thyroid diseases (A. Knezevic
      Obad), breast diseases (I. Kardum-Skelin), gastroenterology and urology (G. Kaic)
      were discussed, as well as technical procedures and the interpretation of the
      cytological findings. Moderator (Z. Znidarcic) opened the panel with presentation
      about the role of clinical cytology, particularly in the primary health care. The
      discussion finally pointed at the necessity of better communication between
      primary practitioners and cytologists. This review article presents contents of
      the panel discussion.

PMID- 20698167
TI  - The role of endoscopic ultrasound in evaluation of gastric subepithelial lesions.
AB  - A subepithelial mass is a common finding during endoscopic procedures. Endoscopic
      ultrasound (EUS) is an important diagnostic modality in the evaluation of
      subepithelial lesions of the gastrointestinal tract. EUS is the diagnostic test
      of choice to assess the size, margins, the layer of origin, echotexture, and to
      differentiate between an intramural and extramural lesion. However, the EUS
      imaging lacks the specificity. EUS-guided fine needle aspiration (EUS-FNA) or
      core biopsy can help establish a tissue diagnosis and potentially characterize
      malignant risk. The aim of this article is to review the diagnosis and management
      of the most common subepithelial gastric lesions with an emphasis on the role of
      endoscopic ultrasound.

PMID- 20698168
TI  - Future perspectives of personalized oncology.
AB  - Based upon an individual's molecular make-up, personalized molecular medicine
      provides information regarding the origin of disease, its treatment and
      progression, while personalized molecular pharmacology advises on drug
      prescription and patient response to it, thus ensuring drug effectiveness and
      preventing drug toxicity or lack of response. Interindividual differences in drug
      responses are mostly due to structural variation in parts of genome, e.g. in
      genes participating in drug metabolism, transport or targeting. However, a wide
      variety of diseases and accompanying health conditions, including patient's
      therapy or drug response, also have epigenetic or epigenomic etiology. High
      priority for personalized oncologic research stems from inter/intraindividual
      tumor heterogeneity provoked by gradual acquisition of multiple random, or
      programmed mutations and rearrangements as well as epigenetic alterations or by
      stochastic fluctuations in cell components, all in tight feedback interaction
      with tumor's environmental or therapy conditions. Natural selection subsequently
      shapes inter/intraindividual tumor heterogeneity by promoting clonal expansion of
      cells that have acquired advantageous mutations for tumor population. Hence, the
      main rationale of personalized molecular oncology should focus on treating
      disease by relying on relevant structure and state of patient's whole molecular
      network (genome/transcriptome/RNome/proteome/metabolome/metabonome) in
      interaction with its unique environmental conditions, thus implying right therapy
      for the right patient at the right dose and time. The future of personalized
      oncology should therefore rely on the methods of systems biology applied in
      cytology and pathology in order to develop and utilize the efficient and
      effective diagnostic, prognostic and predictive biomarkers, consequently
      providing the molecular information on tumor origin, its potential for
      metastasis, adequate therapy, tumor specific therapy responsiveness, and the
      probability of its recurrence.

PMID- 20698169
TI  - Suicidal behavior and suicide among children and adolescents-risk factors and
      epidemiological characteristics.
AB  - In last decade suicide attempts and suicides among youngsters are increasing
      greatly and are one of the leading causes of mortality in this age group.
      Epidemiological data are pointing on more frequent trend of self-destructive
      behavior among youngsters in the world as well as in our country. Risk factors
      which influence on increasing number of suicide attempts and suicides in this age
      are different in etiology: interference of genetic influences, family dynamics
      and external environment (school, friends, social environment, peers, television,
      video, and internet). Croatia as a country in transition is also following trends
      in the world according to epidemiological data, what is for sure great challenge
      for all who participate in dealing with youngsters, especially psychiatric
      services. In the planning of treatment is very important to include family with
      intention to accomplish optimal therapeutic effect. Also, it is very important to
      warn parents on their part of responsibility in upbringing and developing of
      their adolescent.

PMID- 20698170
TI  - Polymorphisms in Toll-like receptor genes--implications for prostate cancer
      development.
AB  - Toll-like receptors are key players in initiation of innate immune response of
      the host. In addition to innate immunity they can also induce adaptive immune
      responses. The concept that inflammation can promote chronic prostatic diseases,
      such as benign prostatic hyperplasia or prostate carcinoma is supported by
      several new findings. Epidemiological data have correlated prostatitis with an
      increased risk of prostate cancer, while PCR-based analyses of bacterial
      colonization in prostate cancer specimens and normal prostate tissue showed high
      correlation of bacterial colonization and chronic inflammation with a diagnosis
      of prostate carcinoma. Even evidence from genetic studies support the hypothesis
      that prostate inflammation may be a cause of prostate cancer. From these points
      of view identification of factors, such as SNPs in TLR genes, associated with
      risk for prostate carcinoma development seems reasonable. Consequently, there are
      many investigations showing the connection between SNPs in TLR genes and
      pronounced susceptibility to different diseases. In this article we review the
      key findings about the genetic variability of TLR genes and prostate cancer risk.

PMID- 20698171
TI  - [The role of interleukin-1 gene polymorphism in gastric carcinogenesis associated
      with Helicobacter pylori infection].
AB  - INTRODUCTION: The search for risk factors of gastric cancer has a long history:
      H. pylori infection is one of them. Unfortunately, there is no reliable method
      for the identification of patients at significant risk of gastric cancer among
      those infected. AIM: To disclose the role of IL-1B gene polymorphism in gastric
      cancer by comparing IL-1B genotypes of patients with different, almost mutually
      exclusive clinical courses. SUBJECTS: We initially enrolled 273 patients and
      continued with 259 patients who tested positive for antibodies against H. pylori,
      including 121 patients with gastric cancer, 119 patients with duodenal ulcer, and
      19 patients with asymptomatic gastritis. The study group included 19 families (48
      patients) with 14 cases of gastric cancer, 15 cases of duodenal ulcer, and 19
      asymptomatic individuals. MATERIAL AND METHODS: The IL-1B gene was sequenced at
      position -511 and -31 using primer extension and mass spectrometry. Intron 2 of
      the IL-1RN gene was studied using PCR and agarose gel electrophoresis. The odds
      ratio (OR) with 95% confidence intervals was computed using logistic regression.
      RESULTS: No association was found between IL-1B gene polymorphism and clinical
      presentation in 19 families. The differences between patients with gastric cancer
      and duodenal ulcer applied only to the C/T variant at position -511 of the IL-1B
      gene after adjustment for family history. Patients with the IL-1B-511 CT genotype
      and negative family history of gastric cancer demonstrated a greater risk of
      gastric cancer compared with patients with positive family history. CONCLUSION:
      Our results suggest a complex association between IL-1B gene polymorphism, H.
      pylori infection, and gastric secretion.

PMID- 20698172
TI  - [Chronic subdural hematoma: a review of the literature. Part 2].
AB  - The second part of this review is concerned with methods and results of treatment
      in chronic subdural hematoma (CSDH). Surgical evacuation is the generally
      accepted approach to treatment in CSDH. There are two neurosurgical methods of
      evacuation: 1. Burr hole in the cranial vault and evacuation of hematoma fluid.
      2. Craniotomy and removal of hematoma with surrounding membranes. According to
      the literature, priority should be given to burr hole evacuation of the hematoma
      on the following premises: 1. High effectiveness with lower risk of complications
      and better treatment outcome for trepanation. 2. Craniotomy with removal of
      hematoma membranes, although radical, does not eliminate the risk of recurrence
      of hematoma. 3. Reduction in the volume of hematoma fluid through the burr hole
      and drainage may lead to total resorption of hematoma together with membranes.

PMID- 20698173
TI  - Does a correlation exist between myopia and dental caries?
AB  - INTRODUCTION: The aim of this study was to analyze the coexistence of myopia and
      dental caries. MATERIAL AND METHODS: 900 children from Elementary School No 3 in
      Szczecin, Poland were examined (443 boys and 457 girls, aged 7-13 years, mean age
      10, SD = 2). The pupils were Caucasian and resided in or near Szczecin. The
      examination included retinoscopy under cycloplegia. Refractive error readings
      were expressed as the spherical equivalent (SE). Myopia was defined as SE of at
      least -0.5 D. Unified WHO criteria were used to evaluate the state of health of
      the oral cavity. The advancement of caries was assessed basing on the mean value
      of dmf and its components for deciduous teeth, as well as on the mean value of
      DMF and its components for permanent teeth. The data was analyzed using Pearson's
      chi2 test and Mann-Whitney U test. P values of < 0.05 were considered
      statistically significant. RESULTS: A high prevalence of dental carries with
      myopia (91.6%) and without myopia (93.8%) was found. Differences between these
      two groups were not statistically significant (p > 0.05, table 1). Furthermore,
      lower values of d (p < 0.01) and dmf (p < 0.001) in deciduous teeth and higher
      values of F (p < 0.05) in permanent teeth were observed in association with
      myopia (table 2). CONCLUSION: No positive correlation between myopia and dental
      caries was ascertained.

PMID- 20698174
TI  - [Diagnostic value of thermography in Raynaud's phenomenon associated with
      systemic lupus erythematosus].
AB  - INTRODUCTION: The study was undertaken to determine of thermographic parameters
      for the assessment of Raynaud's phenomenon in patients with systemic lupus
      erythematosus (SLE). MATERIAL AND METHODS: The study was done in 18 patients with
      SLE and 16 healthy volunteers without vasomotor disorders. Thermography was done
      with ThermaCAM SC500 infrared camera under conditions defined by the European
      Association of Thermology. Measurement of hand temperature preceded the cooling
      test during which the hands in latex gloves were placed in water at 20 degrees C
      for 1 minute. Palm temperature was measured after 0, 5, 10, and 20 minutes from
      removal of hands from water. The average temperature of fingers of both hands was
      calculated. Statistical comparison was done with Student's t-test. RESULTS: 1.
      The average temperature of fingers in patients with SLE was significantly
      different than in controls (p < 0.001). 2. The time of warming up of fingers to
      the starting temperature was longer than 10 minutes in SLE patients and shorter
      than 10 minutes in healthy controls. CONCLUSION: Thermography is useful for the
      diagnosis of SLE.

PMID- 20698175
TI  - [Efficiency of imaging methods for the diagnosis of some congenital defects in
      neonates: personal experience].
AB  - INTRODUCTION: The aim of this study was to assess the efficiency of imaging
      methods for the diagnosis of some congenital defects in neonates. MATERIAL AND
      METHODS: Seventy neonates aged 1 to 30 days, referred to the Department of
      Pediatric and Oncologic Surgery, Pomeranian Medical University, were examined at
      the Department of Diagnostic Imaging and Interventional Radiology. Clinical data
      were analyzed and the imaging method was chosen depending on the clinical
      symptoms of the defect. RESULTS: The following defects were diagnosed:
      gastrointestinal tract defects in 41 neonates (58.5%), urinary tract defects in
      21 neonates (30%), other defects in eight neonates (11.5%) including ovarian cyst
      in four, lung cyst in three, and tumor in the sacrococcygeal region in one
      neonate. The choice of imaging modality was determined by the kind of defect
      deduced on the basis of clinical examination. Ultrasonography was performed in
      all 70 neonates (2-3 times in 25 cases). Radiography was performed in 49 cases,
      including CT in four cases. Defects in the gastrointestinal tract were disclosed
      in most cases except for three of the neonates (7%) in whom the cause of ileus
      remained unknown until surgery when the cause was established (enterogenic cyst
      in two and intestinal sequestration in one neonate). Urinary tract anomalies,
      ovarian cysts, lung cysts, and tumor in the CONCLUSIONS: The efficiency of
      imaging methods in our hands was very high thanks to good cooperation between the
      surgeon and the radiologist. Diagnostic accuracy depends on the kind of anomaly.
      In neonates with urinary tract defects, follow-up examinations preceding planned
      surgery are essential for a good therapeutic outcome.

PMID- 20698176
TI  - [Methods for the assessment of skull asymmetry on radiograms].
AB  - Skull asymmetry is one of the most important points of interest in the analysis
      of radiograms and computed tomography scans done for the purpose of medical
      practice and scientific research. This work reviews methods used to determine the
      presence and degree of skull asymmetry. Assessment of skull asymmetry should
      involve at least two radiographic projections. The midline should be pass through
      vertex (v), crista galli, nasion (n), and prosthion (pr) points in the P-A
      projection and through opisthocranion (op), opisthion (o), basion (b),
      sphenobasion (sphb), and orale (o) in the base projection. Analysis of asymmetry
      of a point should be based on two different points of reference.

PMID- 20698177
TI  - Ionic support of the cough reflex.
AB  - INTRODUCTION: The aim of this study was to determine the role ofintra-wall
      nervous and neurohormonal system in the control of airway transport of sodium and
      chloride ions, as well as to identify regulating mechanisms having an effect on
      the permanent electric potential of airway tissue, named the transepithelial
      electric potential (PD) and on reversible changes of this potential (dPD). Using
      amiloride, a sodium ion blocker, and bumetanide, a blocker of the chloride ion co
      transport system, the importance oftransepithelial sodium and chloride ion
      transport for support of the cough reflex was determined. The conditions were
      identified for examination of chloride secretion in the airways presented as the
      chemical isolation of chloride currents with the use of amiloride. MATERIAL AND
      METHODS: The experimental material consisted of 135 fragments of trachea wall
      obtained from 45 animals. The experiments were directed at measurements of PD of
      the isolated tracheal wall placed in Ussing chamber where this tissue formed an
      interface between two half-chambers filled with an isoosmotic polyelectrolyte
      solution. The main procedure for irritation of sensory receptors in the airways
      utilized ajet from a peristaltic pump directed to the mucous surface of the
      isolated trachea. The jet fluid was analogous to the one in the chamber or it was
      modified as the experimental conditions required. RESULTS: Transepithelial
      transport of sodium ions in the trachea exerted a regulatory effect modulating
      the transepi- thelial difference of electric potentials, as well as inducing
      hyperpolarisation after mechanical stimulation when at 40% the sodium transport
      is the exclusive carrier of the hyperpolarisation reaction.

PMID- 20698178
TI  - [The effect of age on the process of healing of chronic periapical inflammation].
AB  - INTRODUCTION: The aim of this study was to determine the effect of age on the
      process of healing of chronic periapical inflammation. MATERIAL AND METHODS: The
      study was carried out in 59 patients with accidentally disclosed chronic
      periapical inflammation and no other pathology. The patients were allocated to
      two age groups: group I--from 17 to 44 years of age; group II--from 45 to 78
      years of age. All teeth with periapical inflammation were endodontically treated.
      Control radiographs were taken 6 and 12 months later. RESULTS: Radiographs taken
      after 6 months disclosed partial or complete restoration of periapical tissues in
      79.5% of patients in group I and 65.0% of patients in group II. Radiographs after
      12 months showed partial or complete healing in 94.8% of patients in group I and
      90.0% of patients in group II. CONCLUSIONS: The process of healing of chronic
      periapical inflammation lasted longer in patients aged 45-78 years than in
      patients aged 17-44 years. The outcome of treatment was similar in both groups.

PMID- 20698179
TI  - Endodontic and prosthetic treatment of teeth with C-shaped root canals.
AB  - INTRODUCTION: The aim of this study was to describe and discuss the unusual
      anatomy that can be detected during routine endodontic and prosthetic treatment
      of mandibular second molars. MATERIAL AND METHODS: We studied 2 mandibular second
      molars with C-shaped canals in two patients who underwent endodontic and
      prosthetic treatment. In one patient, the preoperative radiograph of mandibular
      right second molar indicated radicular fusion with single apex and two canals.
      However, four separate canals were disclosed during endodontic treatment. There
      were no complications during cleaning, shaping, and obturation of the canals. In
      the second patient, prosthetic restoration of the mandibular left second molar
      after root canal treatment was necessary. The radiograph showed radicular fusion
      with one wide central canal correctly obturated. The tooth was prepared without
      difficulty or complications for the cast post and crown. RESULTS: Endodontic
      treatment in the first patient was successful as confirmed with the postoperative
      radiograph showing precisely obturated canals. The cast post performed in the
      second patient enabled effective tooth reconstruction with a prosthetic crown.
      CONCLUSIONS: C-shaped canals may be precisely debrided and obturated on condition
      that they have been disclosed on preoperative radiographs. Prosthetic
      reconstruction of these teeth with a post-crown is possible but only with the use
      of the distal canal.

PMID- 20698180
TI  - [The influence of polymerization time on physicochemical properties of the
      acrylic resin Vertex RS].
AB  - INTRODUCTION: A good denture can only be produced through proper actions during
      the clinical and laboratory stages of the production process. The aim of this
      study was to determine if a change in polymerization time affects the
      physicochemical properties of polymethacrylate material used for dentures.
      MATERIAL AND METHODS: We examined the acrylic resin Vertex R.S. polymerized for
      15, 25, 40, or 60 minutes. Palapress Vario was taken as reference material.
      Static bending, microhardness, surface wettability, and susceptibility to
      abrasion were determined. RESULTS: The microhardness test showed that most of the
      samples had similar Vickers hardness (VS) values, except for the sample
      polymerized for 25 min. which demonstrated a significantly higher value.
      Grindability was affected by a change in polymerization time. Mass loss was
      greatest for samples polymerized for 15, 25, and 60 min. and smallest for Vertex
      40 and Palapress Vario. We also observed differences in the wetting angle. Vertex
      40 and 60 had a relatively low wetting angle signifying that longer
      polymerization time results in lower hydrophobicity of the material. CONCLUSION:
      The present study has demonstrated that polymerization time has a significant
      effect on the hardness and some mechanical properties of the acrylic resin.

PMID- 20698181
TI  - [Missing maxillary: comprehensive orthodontic and prosthodontic treatment canines
      with endosseous implants].
AB  - INTRODUCTION: Impacted maxillary canines are a serious problem in orthodontics
      and prosthodontics. The incidence of impaction has been reported at 3.3% of the
      general population and is more common among women. Impaction of canines can be
      unilateral or bilateral, palatal or labial. The causes of this pathology are
      varied. Irrespective of the cause of impaction, missing canines represent first
      and foremost an esthetic problem. The aim of this study was to analyze the
      possibilities of reconstructing missing permanent maxillary canines in a given
      clinical situation. MATERIAL AND METHODS: We present the case of a young female
      with bilateral impaction of permanent and retention of deciduous maxillary
      canines. A detailed orthodontic investigation ruled out the possibility of forced
      eruption of impacted canines. Consequently, surgical extraction of impacted
      canines and prosthetic replacement of missing teeth using endosseous implants
      were done. RESULTS: The immediate functional and esthetic result in the patient
      was very good. As prosthetic crowns were cemented to the implants on the day of
      implantation, soft tissues received support without risk of contour change. The
      procedure ensured comfort for the patient without the need of wearing removable
      partial dentures. CONCLUSIONS: 1. Missing permanent canines represent a
      significant esthetic defect of dentition. 2. Surgical extraction and
      reconstructive treatment is an option when forced eruption of impacted canines
      proves impossible. 3. Close cooperation between the orthodontist and implant
      prosthodontist is necessary for a satisfactory esthetic result.

PMID- 20698182
TI  - [Aggression as the cause of stress among physicians].
AB  - INTRODUCTION: Mental stress is inseparably connected with work. The stress
      reaction is favored by stagnation in life, lack of prospects for professional
      growth, uncertainty of stable employment, pressure to work reliably and flexibly,
      excessive workload, and lack of assigned duties. Interpersonal relations among
      members of the team represent another significant factor in the appearance and
      persistence of social pathology. STUDY OBJECTIVES: Identification of forms and
      sources of aggression implicated in stress among physicians at the workplace.
      MATERIAL AND METHODS: The study was performed in 501 physicians employed by
      inpatient and outpatient institutions in the province of Podlaskie. We used
      questionnaires assessing the intensity and type of aggression against physicians
      and the GHQ28 General Heath Questionnaire. RESULTS: The patient source of stress
      for physicians included hostile comportment (53%) and extortion (41%). The source
      of stress from superiors included vulgar acts in the presence of coworkers (18%)
      and threats (17%). Stress was also caused by raised voice of other physicians
      (44%) and nurses (25%). CONCLUSIONS: The main source of stress for physicians was
      aggression by patients and fellow physicians.

PMID- 20698183
TI  - [Exposure of medical rescuers to aggression at the workplace].
AB  - SUMMARY: Members of the medical rescue team are exposed to several dangerous and
      harmful factors, including emotional and physical stress, during their activities
      at the site of an accident. Basing on the literature it can be concluded that
      anxiety and low mood are present in each patient in a state of endangered life or
      health. The aim of study was to assess the incidence, sources, and types of
      aggression against medical rescuers depending on the place of work. MATERIAL AND
      METHODS: This study was done in 126 medical rescuers working in the province of
      Podlaskie. Questionnaires assessing the degree and types of aggression against
      medical rescuers and the GHQ28 General Heath Questionnaire were used. RESULTS:
      Rescuers working in emergency rooms and ambulances reported that aggression most
      often was in the form of raised voice (95%), threats (85%), attempted assault and
      dangerous situation (91%). According to respondents working at hospital emergency
      departments, raised voice is most often encountered (95% of respondents). Threats
      were made against 72%, dangerous situations were noted by 59%, and attempted
      assault was experienced by 44% of respondents. CONCLUSIONS: Rescuers working in
      ambulances and emergency rooms were more often exposed to aggression than
      rescuers working at hospital emergency departments. The exception was raised
      voice by patients which was noted with the same frequency irrespective of the
      place of work. Aggression from superiors and coworkers was evidently more often
      experienced in ambulances and emergency rooms.

PMID- 20698184
TI  - [The impact of illness on the emotional life of women united in "the amazons"
      clubs after breast cancer surgery].
AB  - INTRODUCTION: Breast cancer is the most frequent malignant tumor diagnosed among
      women in Poland and in the world. Among the consequences of the disease are
      disorders in the woman's physical, mental, and social sphere of functioning.
      MATERIAL AND METHODS: We enrolled 102 women aged 29-56 years from three Amazons
      Clubs (mastectomy support groups) in Bydgoszcz, Koszalin, and Bialogard. A
      questionnaire was prepared addressing demographics and the emotional state of
      women. RESULTS: Most of the women participating in our study completed university
      education, had a white-collar job, and resided in a city. The disease completely
      changed the life of 24 women (23%) and some aspects of life of 59 women (58%).
      The disease inflicted changes in the life of 62 (61%) women, with 32 women (31%)
      continuously worrying about their future. Sadness and fear were frequent
      reactions to the diagnosis in 42 women (45%) but only 7 women (7%) felt depressed
      or indifferent to the diagnosis. 42 women (46%) presented a very optimistic
      attitude to the disease and 36 women (39%) were determined to combat the disease.
      The disease had no influence on the life of 19 women (19%). The most frequent
      state after treatment was impatience, feeling of kindness, and irritability
      (32%). CONCLUSIONS: The disease had a negative influence on the emotional state
      of women after mastectomy. An optimistic attitude was observed in almost half of
      the women. Married women and women living in complete families were quicker in
      accepting changes which occurred in their life.

PMID- 20698185
TI  - [Burnout as an occupational risk for nurses].
AB  - INTRODUCTION: The professional activity of a human being can be the source of
      satisfaction and fulfillment but also of frustration and discontent. Professions
      involving contacts with people (nursing, medicine, teaching) carry the risk of
      burnout as a consequence of long-term stress and inefficient coping with
      professional burdens. Burnout may have a negative impact on the physical,
      psychic, emotional, familial and professional spheres of life. The aim of this
      study was to determine the frequency of burnout among nurses and their knowledge
      about methods of protection against burnout. MATERIAL AND METHODS: We performed a
      questionnaire survey in 100 nurses working in the province of Podkarpackie.
      RESULTS: More than half of the surveyed nurses (56%) declared that they chose
      their job to help others, while 15% gave priority to the prestige of this
      profession. According to 80% of the respondents, lack of respect for the nurse
      represents the most stressful factor at work. This is followed by complaints from
      patients and their families (71%), patients under the influence of alcohol (44%),
      and fast pace of work (27%). 39% of the nurses diagnosed themselves with burnout,
      while 35% believed they were at risk of burnout.

PMID- 20698186
TI  - [A model of healthcare for children with hearing disorders].
AB  - Hearing disorders have risen today to the status of a civilization disease.
      Hearing loss during development or the prelingual age is an enormous problem for
      the child. Undiagnosed in time, hearing loss may lead to serious limitations in
      intellectual, cognitive, and emotional development of the child, and to
      difficulties in speaking, writing, reading, and memorising. This paper presents
      current structural solutions regarding healthcare for children with hearing
      disorders. The system of early detection of hearing disorders (mainly inborn) is
      coherent for neonates and small children but lacks a well-coordinated healthcare
      model for older hearing-impaired children, especially in the context of
      disclosing acquired hearing defects. A model of healthcare for children with
      hearing disorders covering every stage of development (age) is presented, aiming
      at improvements in the system of early detection of inborn and acquired hearing
      defects. The model provides for systematic monitoring of patients with hearing
      defects and offers the opportunity of early intervention. Furthermore, the model
      serves to follow the developmental dynamics of the communication process.

PMID- 20698187
TI  - [Empirical studies of care in nursing].
AB  - INTRODUCTION: The scope of the term "care" and of related "caring" and "nursing
      care" is implicated in the range of relevant research. By measuring variables
      assigned to structural elements of care it is possible to undertake empirical
      verifications. OBJECTIVE: This work was undertaken to present and analyze the
      existing research tools used for measuring care/caring in nursing. METHODS: Our
      analysis of the existing research tools for measuring care/caring was done
      according to the criterion of specificity and distinctiveness. RESULTS: Research
      tools used for measuring care/caring in nursing comprise items belonging to two
      basic--technical and emotional--dimensions. Data are collected from the patient,
      the nurse, or the observer. CONCLUSIONS: The comparability of measurements of
      care variables is achievable only if reliable tools are used in nursing research.

PMID- 20698188
TI  - Assessment of postural balance function.
AB  - Postural balance is defined as the ability to stand unassisted without falling.
      Examination of the patient's postural balance function is a difficult diagnostic
      task. Most of the balance tests used in medicine provide incomplete information
      on this coordination ability of the human body. The aim of this study was to
      review methods of assessment of the patient's postural balance function,
      including various tests used in medical diagnostics centers.

PMID- 20698189
TI  - Mostly empty words--what the discourse of "choice" in health care does.
AB  - PURPOSE: This paper has two purposes: one is to analyse how the policy of freedom
      of choice emerged and was formed in the Swedish health care discourse; the second
      is related to how free choice influences the discourse in health care and how
      subjects are formed within the field, i.e. what the language of choice in health
      care does. DESIGN/METHODOLOGY/APPROACH: The research strategy is inspired by a
      combined theoretical framework borrowed from Michel Foucault's concepts of
      "discursive formation" and "subjectivization" completed with Judith Butler's
      concept of performativity. FINDINGS: The language of "freedom of choice" calls to
      mind the rhetoric of promises, i.e. that the patient should be free and
      responsible, in his or her relation to health care. Since patients seem to be
      insufficiently informed and supported about the actual benefits of possibilities
      and limitations associated with the severely restricted reform of free choice,
      the statements concerning opportunities to make personal health decisions will
      lose their significance. The advocacy of discourses of freedom of choice seems
      therefore mostly like empty words, as they are producing weak patients instead of
      free and empowered people. RESEARCH LIMITATIONS/IMPLICATIONS: As the reform was
      initiated in the beginning of 2000 it is rather fresh. ORIGINALITY/VALUE: The
      paper produces insights into the rhetoric of political promises and the
      limitations of the reform dealing with freedom of choice in health care.

PMID- 20698190
TI  - The practice of complexity: review, change and service improvement in an NHS
      department.
AB  - PURPOSE: In the last five years more and more scholars have drawn on insights
      from the complexity sciences as a way of understanding the process of managing
      and organising in the NHS differently. This paper aims to describe working
      methods derived from the theory of complex responsive processes, a more radical
      interpretation of these insights, used by a consultancy team in one NHS setting.
      DESIGN/METHODOLOGY/APPROACH: The authors were invited to undertake this
      intervention over a two year period to bring about service improvement. The paper
      sets out a critique of systems theory, which underpins most management
      literature, as well as offering a critique of some of the ways that complexity
      theory gets taken up in the health literature. As an alternative it explores the
      theoretical underpinnings of complex responsive processes and gives practical
      examples of methods that the authors believe are more suitable for understanding
      the complex environment NHS staff work within. FINDINGS: Working with ideas of
      ambiguity, paradox and complexity are not easy for staff educated in a Western
      tradition of linear cause and effect. However, as a result of this intervention
      managers and staff pointed to a much greater confidence and skill in dealing with
      the complex daily process of organising, which they attribute to the methods
      used. Although the authors make no claim that service improvement arose as a
      direct consequence of the methods employed, significant, observable improvements
      in service provision did occur during and after the consultancy intervention.
      ORIGINALITY/VALUE: The description of working methods based on reflective and
      reflexive group processes, alongside more empirical data-gathering methods, is
      offered as a radical alternative to more orthodox ways of understanding, and
      attempting to work with change in the NHS.

PMID- 20698191
TI  - Critical perspectives in the study of nursing work.
AB  - PURPOSE: The purpose of this article is to critique extant nursing research on
      nursing practice environments by juxtaposing it with critical sociological
      perspectives on nurses' work and to propose an alternative paradigm for future
      research based on these perspectives. DESIGN/METHODOLOGY/APPROACH: The extant
      nursing/health services research on nursing practice environments is reviewed.
      Sociological concepts are introduced, expanded on, and linked to the variables
      measured in the nursing literature. FINDINGS: The substantial body of nursing
      research about nurses' job satisfaction has been targeted to management concerns
      and has taken the positivistic perspective that is traditional in organizational
      research. However, attempts to address nurses' working situations using expedient
      solutions obscure any consideration of underlying influencers. Several well
      developed sociological concepts pertaining to gender, knowledge,
      professionalization, and organizations have direct relevance for the study of
      nurses' work and can provide new perspectives for deeper questioning about
      nurses' work experiences. ORIGINALITY/VALUE: Unprecedented organizational
      restructuring in health care has had a profound impact on the practice of
      nursing, prompting health system administrators and nursing researchers to study
      the consequences of system change and devise solutions. This paper presents a
      discussion of typically disconnected perspectives in the study of work
      (management and sociological) in order to reframe what is known about the factors
      influencing the quality of nurses' working lives and to provide a conceptual
      foundation for deeper and more critical research about nurses' work.

PMID- 20698192
TI  - What can be expected of information and communication technologies in terms of
      patient empowerment in health?
AB  - PURPOSE: Implementing information and communication technologies (ICT) is often
      mentioned as a strategy that can foster public involvement and responsibility in
      health. The purpose of this paper is to provide a better understanding of the
      possibilities and issues afforded by the social uses of ICT for personal
      empowerment in health. DESIGN/METHODOLOGY/APPROACH: The paper discusses evidence
      from four case studies that characterize current computerization and networking
      processes in health. The studies shared a global framework comprising four
      interpretative paradigms of personal empowerment: the professional, technocratic,
      consumerist and democratic paradigms. FINDINGS: The results show the coexistence
      of four empowerment logics in ICT use. Two trends proved dominant: a
      strengthening of the control and standardization processes tied to the typical
      power relationships in health, and a reinforcement of personal autonomy and self
      assertion processes, either through commercial relationships or through the
      social relationships that are also present. PRACTICAL IMPLICATIONS: The paper
      supports the argument that in order to understand the opportunities for personal
      empowerment offered by ICT the logic underlying user practices in their
      respective contexts must be examined. ORIGINALITY/VALUE: The paper uses data from
      four case studies to illustrate the contradictory logics shaping the personal
      empowerment process. Under these logics, an ICT user may play roles as patient,
      client, consumer, or citizen.

PMID- 20698193
TI  - High performance work systems and employee well-being: a two stage study of a
      rural Australian hospital.
AB  - PURPOSE: This paper aims to explore the attitudes of managers and employees to
      high performance work practices (HPWS) in a medium sized rural Australian
      hospital. DESIGN/METHODOLOGY/APPROACH: The study consists of two stages. Stage
      one involved a qualitative investigation consisting of interviews and focus group
      sessions with senior, middle and line management at the hospital. Bowen and
      Ostroffs framework was used to examine how strategic HRM was understood,
      interpreted and operationalised across the management hierarchy. Stage one
      investigates the views of managers concerning the implementation of strategic
      HRM/HPWS. Stage two consisted of a questionnaire administered to all hospital
      employees. The mediation effects of social identification on the relationship
      between high performance work systems and affective commitment and job
      satisfaction are examined. The purpose of stage two was to investigate the views
      and effects of SHRM/HPWS on employees. It should be noted that HPWS and strategic
      HRM are used inter-changeably in this paper. FINDINGS: At the management level
      the importance of distinctiveness, consistency and consensus in the
      interpretation of strategic HRM/HPWS practices across the organization was
      discovered. Findings indicate that social identification mediates the
      relationship between HPWS and affective commitment and also mediates the
      relationship between HPWS and job satisfaction. PRACTICAL IMPLICATIONS: High
      performance work systems may play a crucial role facilitating social
      identification at the unit level. Such practices and management support is likely
      to provide benefits in terms of high performing committed employees.
      ORIGINALITY/VALUE: The paper argues that team leaders and managers play a key
      role in building social identification within the team and that organizations
      need to understand this role and provide recognition, reward, education and
      support to their middle and lower managers.

PMID- 20698194
TI  - Health improvement: countervailing pillars of partnership and profession.
AB  - PURPOSE: The Scottish Parliament has recently formed Community Health
      Partnerships (CHPs), in which health and social care providers come together
      within a unified organisational framework. This paper aims to assess the extent
      to which employees identify with their profession and whether professional
      identity poses a significant barrier to multi-disciplinary, inter-organisational
      partnership. DESIGN/METHODOLOGY/APPROACH: The study adopted a mixed methodology
      approach. A survey of all CHP staff was conducted, four months after the CHP was
      created and obtained a 31 per cent response rate. Additionally, to obtain an in
      depth understanding of the partnership, 26 interviews were conducted with senior
      and middle level managers and professional representatives. FINDINGS: A strong
      professional identity in the health and social care context was evident while the
      partnership vision, in contrast, lacked clarity. Therefore under these
      circumstances individuals' sense of occupation has been heightened due to
      perceived attempts to erode their professional identity, and modifications to
      their sense of "self" have not been challenged by a strong partnership ethos.
      PRACTICAL IMPLICATIONS: Managers face a deep-rooted cultural based challenge
      where individuals strongly identify with their profession rather than the ethos
      of the partnership, which impedes full integration. Managers have a "balancing
      act" of addressing structural and processual change within the integration
      agenda, without losing sight of the outcomes in terms of service delivery and
      improving health and wellbeing. ORIGINALITY/VALUE: This paper examines the
      implications of a new major health policy change that aims to integrate health
      and social care. In addition, the study unravels the complex issue of
      professional identity in this context.

PMID- 20698195
TI  - A forgotten cause of false negative rapid urease test: formalin contamination of
      the sample.

PMID- 20698197
TI  - Overcoming the difficulties encountered when performing laparoscopic
      cholecystectomy: review of over one thousand laparoscopic cholecystectomies.
AB  - BACKGROUND/AIMS: We assessed the safety of intraoperatively managing the
      complications that are encountered during laparoscopic cholecystectomy.
      METHODOLOGY: From September 2003 to November 2006, one thousand thirty four
      patients underwent laparoscopic cholecystectomy for benign gallbladder diseases.
      Laparoscopic cholecystectomy was adopted as the first line treatment for all of
      these patients regardless of the diagnosis or the presence of previous abdominal
      operation. RESULTS: There were 464 male patients and 570 female patients, with a
      mean age of 53.0 years. Two hundred ninety seven patients (28.7%) had a previous
      history of abdominal operation. The mean operation time was 51.6 minutes and the
      mean postoperative hospital stay was 3.8 days. All 9 intraoperative injuries
      during laparoscopic cholecystectomy were successfully managed by laparoscopic
      procedures such as choledochocholedochostomy and laparoscopic repair of the
      injured organ, while no open conversion was required. The complication rate was
      similar between the patients with or without a previous history of operation.
      CONCLUSIONS: Laparoscopic cholecystectomy had been successfully performed without
      open conversion even in patients with acute cholecystitis or in those who have a
      previous history of abdominal operation. Most of the complications encountered
      during laparoscopic cholecystectomy can be managed laparoscopically.

PMID- 20698196
TI  - Detection of gastric cancer cells in the blue lymph node and lymphaticus under
      sentinel lymph node biopsy using dye technique alone.
AB  - BACKGROUND/AIMS: We investigated whether or not there are cancer cells in the
      blue node (BN) and the sentinel lymphaticus (SL), which is detected using
      sentinel node biopsy (SNB). METHODOLOGY: Patent blue (1%) is injected
      submucosally into 4 to 5 different sites at 1 mL per site around the primary
      tumor. Blue-stained lymphatics and lymph nodes can be seen by turning over the
      greater omentum and lesser omentum extraperitoneally. If blue nodes or
      lymphaticus are found, biopsy is performed at this point. The study was conducted
      in 14 patients (11 males and 3 females, mean age 65.7 y/o) with a preoperative
      diagnosis of T1 tumor invasion and NO that there is no lymph node metastasis.
      Informed consent was obtained from the patients for SNB after patent blue
      staining and investigation of CEAmRNA and CK20mRNA. RESULTS: Of the 14 patients
      in whom BN and SL were identified, 1 (7.1%) had positive CEAmRNA and positive
      CK20mRNA of SL. CONCLUSION: Our present study shows the possibility for the
      existence of cancer cells in the lymphaticus from the tumor to BN. We should
      avoid the cut of lymphaticus when we perform gastrectomy.

PMID- 20698198
TI  - Evaluation of the POSSUM score in surgical treatment of cholangiocarcinoma.
AB  - BACKGROUND/AIMS: The surgical treatment for cholangiocarcinoma (CCC) is still a
      challenge. The aim of this study was to evaluate the POSSUM scoring system for
      preoperative physiological risk adjustment and for the operative risk of
      postoperative morbidity and mortality. METHODOLOGY: The operative notes and
      hospital files of 171 patients with CCC were analyzed retrospectively. The POSSUM
      scoring system was used to predict morbidity and mortality rates after surgery.
      The physiological sub score and the operative sub score of the POSSUM score were
      analyzed with regard to their ability to predict major postoperative
      complications. RESULTS: The overall complication rate was 40.9% and the mortality
      was 11.2%. The morbidity predicted by POSSUM was 63.5% and the prediction for
      postoperative mortality was 23.7%. Both rates are much higher than the observed
      morbidity and mortality. High operative severity sub scores correlate with the
      occurrence of major complications. CONCLUSION: The POSSUM scoring system over
      predicts morbidity and mortality in surgery for CCC. Operative severity and
      intraoperative parameters have a greater influence on postoperative mortality and
      morbidity rates than the physiological parameters represented in the POSSUM
      physiological score. Prospective studies will have to show whether POSSUM can be
      modified or whether it is necessary to develop a new score for assessing
      morbidity and mortality in surgery for CCC.

PMID- 20698199
TI  - Early laparoscopic cholecystectomy for acute gallbladder disease in Chinese
      elderly.
AB  - BACKGROUND/AIMS: Evidence now strongly supports that early laparoscopic
      cholecystectomy (ELC) is the treatment of choice for acute gallbladder disease.
      However, the optimal time for managing acute gallbladder disease in elderly
      people is still controversial. The purpose of this study was to evaluate the
      outcome of ELC in patients aged 65 years old and older. METHODOLOGY: We performed
      a retrospective case study review of patients undergoing ELC in a single
      institution between January 2005 and December 2008. RESULTS: A total of 4048
      patients were analyzed: 737 patients were older than 65 years old and 3311
      younger. In total, 18% of the elderly patients and 3% of the younger patients had
      American Society of Anesthesiologists (ASA) score III and IV, respectively (p <
      0.001). Co-morbidity rates were significantly higher in the elderly group (61.5%
      vs. 20.7%, p < 0.001). There was no difference in operative time, intraoperative
      complications, hospital stay and mortality between the two groups, except that
      the rate of conversion to open cholecystectomy (OC) and postoperative
      complications were significantly higher in elderly patients. CONCLUSION: Even
      though elderly patients are more likely to present with several co-morbidities in
      advanced stages, ELC for elderly patients with acute gallbladder disease is safe
      and effective, and should be regarded as the standard of care.

PMID- 20698200
TI  - Pre-operative biliary drainage in hilar cholangiocarcinoma, benefits and risks,
      single center experience.
AB  - BACKGROUND/AIMS: Post-operative hepatic insufficiency is a critical complication
      after hepatic resection in jaundiced patients with hilar cholangiocarcinoma
      (hilar CC). Attempts to reduce the post operative risks associated with biliary
      obstruction by preoperative biliary drainage (PBD) remain controversial.
      METHODOLOGY: This study comparing 100 patients with hilar CC who underwent
      different types of hepatectomy with PBD (46%) [through percutaneous transhepatic
      drainage (PTD), endoscopic retrograde cholangiopancreatography (ERCP), or both]
      and without PBD (54%). Morbidity and mortality were analyzed. RESULTS: Morbidity
      was 58.6% in the drained group and 20.3% in the undrained group (p = 0.001).
      Wound infection, abdominal collection and pneumonia were frequent in the drained
      group. Biliary leakage had a significant occurrence in the drained group (p =
      0.02). Transfusion requirement was more common in the drained group (p = 0.04).
      Post operative hospital stay was prolonged in the drained group (p = 0.01).
      However, transient liver cell failure was more common in the undrained group
      (14.8% vs. 10.8%). In contrast, there were no significant differences for
      mortality (10.8% vs. 5.5%, p = 0.14), survival (22.6 +/- 17 vs. 19.7 +/- 16.6
      months, p = 0.27) and recurrence (26% vs. 18.5%, p = 0.65). CONCLUSION: Major
      liver resections in hilar CC without PBD are safe in most patients. PBD increases
      morbidity, biliary leakage, transfusion requirement and hospital stay. In our
      experience, PBD is recommended in selected patients with: cholangitis, long
      standing jaundice, impaired renal function and severe malnourishment state.

PMID- 20698201
TI  - Clinical/pathological analysis of gallbladder adenomyomatosis; type and
      pathogenesis.
AB  - BACKGROUND/AIMS: The aim of this study was to analyze the clinical/pathological
      outcomes of patients that underwent surgery for gallbladder adenomyomatosis, to
      clarify the characteristics of the type and pathogenesis of adenomyomatosis.
      METHODOLOGY: From May 1997 to March 2008, 4704 consecutive patients underwent
      cholecystectomy at Ajou University Medical Center. Among them, 113 (2.4%)
      patients that were histopathologically diagnosed with adenomyomatosis or
      adenomatous hyperplasia were selected for this study. The patients were divided
      into a fundal type group and a segmental/diffuse type group, and the specimens
      reviewed with Hematoxylin-Eosin (H & E) and immunohistochemical stainings.
      RESULTS: Sixty-three patients were male and 50 female; the age ranged from 17 to
      76 years of age. The fundal type was the most common type. Gallstones were
      present in 69.9% of the patients. In the analysis of the fundal and
      segmental/diffuse types, gallstones were present in 23 patients with fundal type
      and in 53 patients with segmental/diffuse type; this difference was statistically
      significant (p < 0.05). Review of H & E staining showed that the most common
      findings were grade 1 (n = 14) in the fundal type and grade 2 (n = 23) in the
      segmental/diffuse type; there was a significant difference in the inflammatory
      grade (p < 0.05). Immunohistochemical staining showed expression of vimentin, as
      a mesenchymal marker in 28.0% of cases (n = 16). CONCLUSIONS: The fundal type
      differed from the segmental/diffuse type based on the clinical/ pathological
      features; it had a lower frequency of gallstones and a lower inflammatory grade.
      In addition, no cancer was identified in the resected gallbladders of patients
      with adenomyomatosis. The findings suggest that the Rokitansky-Aschoff sinuses
      (RAS) were associated with acquired motility, based on the expression of
      vimentin, consistent with an epithelial-mesenchymal transition.

PMID- 20698202
TI  - Effective treatment of advanced cholangiocarcinoma by hepatic arterial infusion
      chemotherapy combination with sorafenib: one case report from China.
AB  - BACKGROUND/AIMS: Cholangiocarcinoma, especially intrahepatic type, is difficult
      to be found early and diagnosed at early stages. Although it was reported as rare
      to happen, it is a well-known devastating malignancy with little treatment
      effects. As a result, most of the patients suffer from poor prognosis. On the
      other hand, the incidence of intrahepatic cholangiocarcinoma arises worldwide.
      Radical surgical resection was regarded as the most effective treatment, in spite
      of recurrence. Unfortunately, only 30 percent of patients qualify for this at the
      time of diagnosis. Hence, for advanced cholangiocarcinoma, chemotherapy is the
      only modality left to be chosen. Recently LaRocca and Kudoh reported about
      effective chemotherapy for cholangiocarcinoma. Even so, because of no randomized
      study, no standard chemotherapy for cholangiocarcinoma has been accepted, and
      most of the projects were based on 5-Fu. Sorafenib, a multikinase inhibitor,
      which can competitively inhibit RAF/MEK/ERK pathway, human vascular endothelial
      growth factor receptors (VEGFR2, VEGFR3) platelet-derived growth factor receptor
      beta (PDGFR), Flt3, and C-kit receptors, has been successfully applied for solid
      tumors such as renal cancer and hepatocellular carcinoma. Sorafenib used alone or
      in combinations, can induce growth-inhibition and apoptosis in vitro experiments.
      Application of sorafenib alone for cholangiocarcinoma has also been published.
      The role of combination with other chemotherapy drugs in advanced
      cholangiocarcinoma still needs to be defined. METHODOLOGY: A patient admitted for
      exploratory operation was demonstrated to be suffering from unresectable, biopsy
      proven intrahepatic cholangiocarcinoma. A pump was placed inside hepatic artery,
      for the purpose of infusion chemotherapy. Program of chemotherapy was scheduled
      and hepatic arterial infusion of 5-Fu/LV +oxaliplatin +hydroxycamptothecine was
      performed. Three months later, no effect was discovered, so sorafenib was
      suggested to combine with infusion chemotherapy. For the first time we applied
      sorafenib combination to hepatic arterial infusion chemotherapy RESULT: After
      lower dosage of sorafenib was used as a combination with hepatic arterial
      infusion chemotherapy, size of hepatic lesions and level CA19-9 of peripheral
      blood count were decreased, without any damage to the hepatic function, except
      for temporary skin hyperkeratosis as well as vomit. Efficacy of treatment was
      demonstrated by computed tomography (CT) scan. CONCLUSION: So far as in our
      patient, the application of sorafenib combination with other agents through
      hepatic arterial infusion chemotherapy may be an effective way for
      cholangiocarcinoma, but the definite mechanism has to be confirmed by methods of
      molecular biology.

PMID- 20698203
TI  - The variation of expression of CD4+ CD25+ Foxp3+ regulatory T cells in patients
      with Helicobacter pylori infection and eradication.
AB  - BACKGROUND/AIMS: H. pylori persists for the virtual life of its host. Recent
      studies suggested that CD4+ CD25+ regulatory T cells may be involved in this
      process. However, the alteration of CD4+ CD25+ regulatory T cells after
      eradication of H. pylori remains a question. METHODOLOGY: By using biopsies from
      45 H. pylori-positive patients and the ones after eradication of H. pylori and 35
      H. pylori-negative adults, real-time PCR and general PCR were used to quantify
      the expression of Foxp3 mRNA. IHC was used to semi-quantify the number of CD4+
      CD25+ T cells in gastric mucosa. RESULTS: We found that proportion of CD25+ T
      cell in CD4+ T cells accounted for 0.739% in H. pylori-negative individuals,
      while it was accounted for 5.012% in H. pylori-positive patients. After
      eradication of H. pylori, proportion of CD25+ T cell in CD4+ T cells declined (p
      < 0.01) and it accounted for 0.551%. The level of Foxp3 mRNA significantly
      decreased (p < 0.01) in gastric mucosa of patients after eradication of H.
      pylori. CONCLUSIONS: CD4+ CD25+ regulatory T cells decreased in gastric mucosa
      when patients received eradication of H. pylori. Eradication of H. pylori results
      in the significant descrease of Foxp3 mRNA in gastric mucosal, or using the drugs
      of anti-H. pylori induce the reduction of gastric mucosal Foxp3 mRNA expression,
      which is the a key regulatory gene for the development and function of CD4+ CD25+
      regulatory T cells, thus contributing to the eradication of H. pylori. All the
      data offer new possibilities that Foxp3 gene may be the new target of
      immunization intervention strategies for eradication of H. pylori.

PMID- 20698204
TI  - HCC in young adults.
AB  - A large cohort of unresectable and untransplantable biopsy-proven HCC patients
      was rank-ordered for survival. Non-random clustering by age was noted, with 3 sub
      cohorts of younger patients with survival in the range of 90-360 days. One sub
      cohort had a predominance of females. Tumor numbers were well monitored by serum
      AFP, but tumor mass was better monitored by serum GGTP. In contrast to the older
      patients, the probability of hepatitis appeared to have a major impact on their
      survival and these patients tended to have larger numbers of smaller tumors,
      consistent with the idea of a hepatitis-mediated carcinogenic field defect.

PMID- 20698205
TI  - Therapy response and outcome of overlap syndromes: autoimmune hepatitis and
      primary biliary cirrhosis compared to autoimmune hepatitis and autoimmune
      cholangitis.
AB  - BACKGROUND/AIMS: We have assessed two different overlap syndrome groups in
      patients with AIH-PBC and AIH-AIC, with respect to therapy response and outcome.
      METHODOLOGY: In this retrospective, non-randomized study, a total of 22 overlap
      cases were collected, 12 of those had a simultaneous form of AIH-PBC and 10 of
      those with AIH-AIC. Two groups were compared in terms of clinical, biochemical,
      immunological, histological features and response to treatment. The mean follow
      up time was 31.7 +/- 11.0 mo in AIH-PBC and 41.1 +/- 29.6 mo in AIH-AIC,
      respectively. RESULTS: The clinical and laboratory characteristics at
      presentation were not significantly different between the two groups, except a
      higher serum IgM level and lower AIH score in AIH-PBC group compared to AIH-AIC
      group (p < 0.05). First-line treatment was UDCA alone in 3 of AIH-PBC group and
      combination of UDCA and immunsuppressives in the remaining AIH-PBC (n = 9) and in
      all of the AIH-AIC (n = 10). During follow-up, only one of 10 patients in IIH-AIC
      group, but six of 12 patients in AIH-PBC group progressed to liver failure. So,
      complete remission was significantly higher in the AIH-AIC than in the AIH-PBC
      group ( % 90 vs % 50, p = 0.045). CONCLUSION: To our results, in cases of AIH
      PBC/AIC overlap, patients with high AIH score and negative AMA should be treated
      with combined therapy of corticosteroids and UDCA. However, patients with low AIH
      score and positive AMA should use UDCA firstly, if no response, the addition of
      corticosteroids should be considered with close monitoring. In this cohort, the
      prognosis of AIH-PBC overlap was much worse than that of AIH-AIC.

PMID- 20698206
TI  - FDG-PET/CT findings of autoimmune pancreatitis.
AB  - BACKGROUND/AIMS: This study aimed to evaluate the clinical utility in Fluorine-18
      fluorodeoxyglucose-positron emission tomography (FDG-PET)/ computed tomography
      (CT) in the management of patients with autoimmune pancreatitis (AIP), with
      special emphasis on differentiating AIP from pancreatic cancer (PC). METHODOLOGY:
      FDG-PET/CT findings of 10 AIP patients were compared with those of 14 PC
      patients. RESULTS: There were no significant differences between AIP and PC in
      early and delayed maximum standardized uptake value (SUV(max)), and in the ratio
      of delayed to early SUV(max). Abnormal extrapancreatic FDG uptake was observed in
      5 AIP patients, in the hilar lymph nodes (n = 4), mediastinal lymph nodes (n =
      2), abdominal lymph nodes (n = 2), and bilateral salivary glands (n = 2). After
      steroid therapy, the abnormal FDG uptake in the pancreas disappeared almost
      completely in two patients, and the FDG uptake in the hilar, mediastinal and
      abdominal lymph nodes decreased in one patient. CONCLUSIONS: FDG-PET/CT may be
      helpful to differentiate AIP from PC by assessing FDG-uptake patterns in the
      pancreas and extrapancreatic lesions, it may have the potential to assess the
      disease activity of AIP and its extrapancreatic lesions, and it may be useful as
      a monitoring marker for tapering or stopping steroid therapy.

PMID- 20698207
TI  - Hepatobiliary mucinous cystadenoma and cystadenocarcinoma: report of six cases
      and review of the literature.
AB  - BACKGROUND/AIMS: The aim of this investigation was to describe the clinical
      features, diagnosis, pathologic characteristics, and optimal surgical management
      for patients with mucious hepatobiliary cystadenomas (HBCAs). METHODOLOGY: From
      2005 to 2008, our institutional experience for treating six patients with HBCAs
      was reviewed and reported. The clinical features, radiological characteristics
      and management were analyzed retrospectively. RESULTS: Two of six patients were
      respectively misdiagnosed as hydatid cyst and simple cyst pre-operatively. The
      histopathologic examination showed HBCA in four patients and hepatobiliary
      cystadenocaiconoma (HBCAC) in two patients. Three HBCA patients and two HBCAC
      patients had undergone total excision treatment. In a median of 37.5 months
      follow-up visit, four have no evidence of recurrence and one HBCAC patient
      experienced a recurrence 31 months after surgery. Another HBCA patient who
      underwent fenestration initially with subsequent recurrence, died 15 months after
      the therapy. CONCLUSIONS: Owing to its potential for malignant transformation
      into HBCAC, along with the consideration that it tends to recur after incomplete
      resection, radical excision treatment with adequate surgical margins is regarded
      as the most suitable mode of therapy for the HBCA.

PMID- 20698208
TI  - Prognostic effect of human leukocyte antigen class I and II alleles on chronic
      hepatitis C patients treated by pegylated interferon-alfa plus ribavirin in
      Taiwan.
AB  - BACKGROUND/AIMS: To investigate the influence of human leukocyte antigen (HLA)
      class I and II alleles on the response in chronic hepatitis C (CHC) patients
      receiving combination therapy with pegylated interferon-alfa and ribavirin.
      METHODOLOGY: One hundred and six CHC patients who accomplished combination
      treatment were enrolled. Sixty-seven patients achieved sustained virologic
      response (SVR). HLA-A, -B, -C, -DR, and -DQ loci were determined by sequence
      based genotyping. The effects of virologic variables and HLA alleles on SVR were
      evaluated by logistic regressions. RESULTS: Univariate analyses showed that SVR
      was significantly associated with low pre-treatment HCV RNA levels, HCV genotype
      non-1, high pre-treatment ALT levels, a significant decline of ALT levels from
      baseline to week 4, and the low body mass index. Among HLA class I and II
      alleles, the occurrence of SVR was significantly associated with lack of HLA-B60
      and existence of HLA-A33 in univariate analyses (OR, 0.33; 95% CI, 0.14-0.77; p =
      0.01; OR, 2.16; 95% CI, 0.86-5.45; p = 0.30 with a trend, respectively).
      Multivariate analyses revealed that HLA-A33 significantly favored SVR after
      adjusted for potential confounders (OR, 7.86; 95% CI, 1.43-43.30; p value after
      Holm's procedure = 0.03). CONCLUSIONS: HLA-A33 is associated with the achievement
      of SVR in Taiwanese CHC patients receiving combination therapy with pegylated
      interferon-alfa plus ribavirin.

PMID- 20698210
TI  - Evaluation of ulcerative colitis using diffusion-weighted imaging.
AB  - BACKGROUND/AIMS: The aims of this study were to determine the feasibility of
      diffusion-weighted imaging (DWI) for detecting bowel inflammation and to
      investigate the changes in the apparent diffusion coefficient (ADC) values in the
      inflamed bowel of patients with ulcerative colitis (UC). METHODOLOGY: Seven
      patients, who underwent DWI for UC and curative total colectomy because of
      insistence on conservative therapy, were enrolled in this study. The resected
      specimens were examined histopathologically to determine the degree of
      inflammation and the presence of malignancy. The ADC values of the lesions were
      calculated and compared among UC lesions. RESULTS: The mean ADC value of the
      active UC lesions was significantly (p < 0.01) lower than that of the normal
      colorectal tissue (1.12 +/- 0.14 x 10(-3) mm2/s vs. 1.60 +/- 0.21 x 10 (-3)
      mm2/s, respectively). The mean ADC value of the active lesions was significantly
      (p < 0.01) lower than that that of the healing lesions (1.12 +/- 0.14 x10(-3)
      mm2/s vs. 1.62 +/- 0.28 x 10(-3) mm2/s, respectively). CONCLUSIONS: DWI may be
      valuable for following patients with UC, and the stage of UC may be diagnosed
      easily based on the ADC values.

PMID- 20698209
TI  - Endoscopic features of nonampullary duodenal tumors with narrow-band imaging.
AB  - BACKGROUND/AIMS: Endoscopic features of nonampullary duodenal adenomas and early
      adenocarcinomas are not well known. The aims of this study were to investigate
      the endoscopic features of the tumors using conventional endoscopy and narrow
      band imaging magnified endoscopy, and to reveal the relationship between the
      endoscopic features and histological grades. METHODOLOGY: The study included 24
      nonampullary duodenal adenomas and early adenocarcinomas in 22 patients who
      underwent conventional endoscopy and narrow-band imaging magnified endoscopy. The
      tumors were divided into histological groups according to the modified Vienna
      classification system. RESULTS: The 24 tumors were 17 adenomas and 7 carcinomas
      in situ, and divided into 10 Category 3 and 14 Category 4 lesions. On
      conventional endoscopy, 22 of the 24 (92%) lesions, had a milk-white mucosa and
      the frequency of a marginal-type one was significantly higher for the Category 4
      group (p = 0.028). On narrow-band imaging magnified endoscopy, all tumors had a
      heterogeneous pattern. The frequency of an obscure mucosal pattern and a network
      microvascular pattern was significantly higher for the Category 4 group (p =
      0.024 and 0.001, respectively). CONCLUSIONS: Narrow-band imaging magnified
      endoscopy following conventional endoscopy might be a promising approach to
      realizing lesions or predicting histological grade of nonampullary duodenal
      intraepithelial tumors.

PMID- 20698211
TI  - Paraaortic lymph node metastasis showed CR to UFT/LV therapy in elderly rectal
      cancer.
AB  - BACKGROUND/AIMS: Intravenous chemotherapy with a combination of several drugs is
      commonly used to treat metastatic colorectal cancer. However, the associated
      adverse events can be severe. Here we report a rare case of metastatic rectal
      cancer in an elderly patient who got complete response for metastatic rectal
      cancer with oral uracil-tegafur plus leucovorin therapy. METHODOLOGY: 77-year-old
      male. An abdominoperineal resection of the rectum was performed, but para-aortic
      lymph-node metastasis occurred. Uracil-tegafur plus leucovorin therapy was
      started on postoperative day 48. Each chemotherapy course comprised 400 mg/day
      uracil-tegafur and 75 mg/day leucovorin administered for 28 days every 35 days.
      RESULTS: After 10 courses, abdominal computed tomography indicated that a good
      partial response had been achieved. The para-aortic lymph-node swelling
      disappeared after 17 courses, indicating a complete response. During this period,
      no adverse events were noted. No recurrence had occurred 4 months after the
      complete response. CONCLUSIONS: This case demonstrates that uracil-tegafur plus
      leucovorin therapy can be used safely even in elderly patients, and suggests that
      it is likely to be effective in treating metastatic colorectal cancer.

PMID- 20698212
TI  - Prevention of anastomotic leakage after low anterior resection in rectal cancers.
AB  - BACKGROUND/AIMS: To review the available data on the efficacy of the measures
      that are directed towards prevention of anastomotic leakage after low anterior
      resection and introduce a promising method based on our own experience.
      METHODOLOGY: The Medline database was searched for studies on the prevention of
      anastomotic leak after low anterior resection in rectal cancers. RESULTS: Two
      meta-analyses of the results indicate that a routine defunctioning stoma reduces
      the rate of clinically relevant anastomotic leakages and is thus recommended in
      such patients. However, the morbidity of the stoma itself, as well as the
      morbidity and mortality of its closure should also be considered and pending
      further trials to clarify its role. Studies suggested that omentoplasty may
      reduce the leakage rate, but there is a paucity of large randomized trials. A non
      randomized trial together with our clinical experience indicated Valtrac-secured
      intracolonic bypass (VIB) may be a promising method in prevention of anastomotic
      leakage in rectal cancers. CONCLUSIONS: VIB appears so far to be a promising
      method for the prevention of anastomotic leak after low anterior resection in
      rectal cancers. However, further randomized controlled studies are still required
      to determine its clinical efficacy.

PMID- 20698213
TI  - Our experience of total mesorectal excision for rectal cancers.
AB  - BACKGROUND/AIMS: The total mesorectal excision (TME) for rectal tumours was
      introduced in 1982 by Heald et al. and has led both to a 5% de crease of local
      recurrences 5 and 10 years after the operation when compared with cases treated
      with conventional surgery, and to an increase of survival up to five years
      estimated in 80% of all cases. In Italy TME was firstly introduced for distal
      rectal carcinomas about 20 years ago, and has shown the same rate of local
      recurrences reported by Heald. The aim of our work is to highlight TME advantages
      and demonstrate how this more demanding and longer lasting method has an
      acceptable risk for the surgery of rectal tumours. METHODOLOGY: We have compared
      two groups of patients operated for rectal carcinoma; the first, "historical
      control group" (no TME, including 46 patients) was treated with the standard
      surgery technique, while the second group (TME, 47 patients) underwent the total
      mesorectal excision technique. 14 of non TME patients belonged to Dukes stage A,
      20 to stage B and 12 to C; whereas in the TME group 16 patients belonged to Dukes
      stage A, 23 to B and 8 to C. The patients of both groups undergone the exams of
      follow up (blood test, hepatic ultrasonography, abdominal CT, thorax Ro); the
      follow up pattern included periodic controls with a check-up every three and six
      months, from one to five years. RESULTS: Postoperative complications in both
      groups do not show important differences in rates, although, the first group (no
      TME) had 11 cases with postoperative complications confronted with the 8 cases of
      the second group (TME). The complications taken into consideration were:
      anastomotic bleeding (3 patients no TME, 6% vs 1 patients TME, 2%), intestinal
      obstruction (1 patient no TME, 2% vs 1 patient TME, 2%), parietal infection (4
      patients no TME, 9% vs 3 patients TME, 6%), anastomotic fistulae (2 patients no
      TME, 4% vs 2 patients TME, 4%), retention of urine and vesicular disorder (1
      patient no TME, 2% vs 1 patient TME, 2%). Tumours closer to the anus have shown
      more complications compared with tumours at higher levels. As a matter of fact, 9
      cases of no TME and TME patients with low located tumours have undergone
      complications compared with the 3 cases of no TME and TME patients with tumours
      being more distant from the anus; the rest 7 cases belonged to the middle rectum.
      A higher rate of local recurrences was noticed in the no TME group: 6 (13%)
      compared with the TME group: 3 (6%). Other tardy complications taken into
      consideration were: hepatic metastasis (5 patients no TME, 11% vs 4 patients TME,
      8%), pulmonary metastasis (3, 6% of the no TME vs 2, 4% of the TME), anastomotic
      stenosis (4, 9% of the no TME vs 2, 4% of the TME), impotence (2, 4% of the no
      TME vs 1, 2% of the TME). We also noticed that most of the tardy complications in
      the TME group belonged to Dukes stage C. CONCLUSION: From our experience, we
      concluded that, in TME patients, complications are lower than in no TME patients;
      the site of the tumour affects the appearance of complications which are more
      frequently in distal localizations. An important result is the minor incidence of
      local recurrences after TME, which brings us to the conclusion that TME can be
      considered a valid method with an acceptable risk for the surgery of rectal
      tumour.

PMID- 20698214
TI  - Clinicopathological study of colorectal cancer occurring in patients with
      ulcerative colitis: results from a single hospital in Japan.
AB  - BACKGROUND/AIMS: Colorectal cancer (CRC) was first recognized as a complication
      of ulcerative colitis (UC) in 1925, and the increased risk has since been
      confirmed in a multitude of epidemiological studies. To our knowledge, however,
      all of these studies have been conducted in Western countries. The aim of this
      study was to identify the clinicopathological features of ulcerative colitis
      related CRC in a consecutive series of patients at a single hospital in central
      Japan. METHODOLOGY: 314 (170 males, 144 females, mean age 30) consecutive
      patients diagnosed with ulcerative colitis were enrolled and investigated for the
      development of CRC. 240 patients had relapsing-remitting disease, 54 had chronic
      continuous disease, 16 had experienced one attack only, 2 had the acute
      fulminating type, and 2 were unknown. With regard to disease extension, 181 cases
      were of the pan-colitis type, 84 were left-sided colitis, and 42 were proctitis.
      Two patients (1%) had a family history of colorectal cancer and 45 (14%) were
      past or current smokers. RESULTS: Colorectal cancer developed in seven patients
      (male to female ratio of 1:6), which was 2.2% of the total. Average age at the
      onset of ulcerative colitis was 28 years. Average age at the onset of cancer was
      44 years, and average duration of UC at cancer onset was 192 months. Ulcerative
      colitis was of the pancolitis type in all cases. Three patients (43%) showed the
      relapse-remitting type and four (57%) the chronic continuing type. Three patients
      (43%) had a family history of cancer, in particular colorectal cancer in one
      patient (14%). None of the patients had a history of smoking. The histological
      type of cancer was well differentiated tubular adenocarcinoma in three patients
      (43%) and poorly differentiated adenocarcinoma in three patients (43%) each, and
      endocrine cell carcinoma in one (14%). CONCLUSIONS: In this group of Japanese
      patients, development of colorectal cancer was more likely to occur in patients
      with ulcerative colitis that was long-standing, and more extensive than left
      sided colitis, particularly in those with a family history of colorectal cancer,
      inflammatory polyps, or dysplasia. CRCs in our patients with UC were often poorly
      differentiated and had a poor prognosis.

PMID- 20698215
TI  - Pedicled ileal flap for duodenal defect after right hemicolectomy.
AB  - BACKGROUND/AIMS: To describe a convenient approach for repairing a large duodenal
      defect after right hemicolectomy for right side colon neoplasm. METHODOLOGY: Six
      patients with a large duodenal defect after right hemicolectomy with partial
      duodenectomy for right side colon neoplasm were treated with a pedicled ileal
      flap to cover the large duodenal defect. RESULTS: Six cases recovered smoothly.
      There was no perioperative morbidity and mortality in this series, except for one
      patient who had a duodenal leakage but who got well with medical treatment.
      Postoperative radiography showed normal duodenal peristalsis. CONCLUSIONS: The
      pedicled ileal flap procedure for repairing a large duodenal defect after right
      hemicolectomy is safe and convenient, and is especially indicated for elderly
      patients or patients with poor general condition.

PMID- 20698216
TI  - Randomized controlled trial: roxatidine vs omeprazole for non-erosive reflux
      disease.
AB  - BACKGROUND/AIMS: Proton pump inhibitor (PPI) therapy is considered as the first
      choice for treatment of non-erosive reflux disease (NERD). However, NERD is less
      sensitive to PPIs than erosive gastroesophageal reflux disease (GERD) and the
      differences between PPIs and H2 receptor antagonists are less evident in NERD
      than in erosive GERD. Since gastric acid secretion is lower in the Japanese
      population than in Western populations, we aimed to investigate whether PPI
      therapy is really necessary for NERD patients in Japan. METHODOLOGY: Thirty-three
      symptomatic endoscopically diagnosed NERD patients were randomly assigned to
      receive roxatidine acetate 75 mg twice daily (n = 16) or omeprazole 20 mg once
      daily (n = 17). Gastrointestinal symptoms were assessed using the
      Gastrointestinal Symptom Rating Scale at baseline and after 4 and 8 weeks of
      treatment. RESULTS: Both roxatidine and omeprazole significantly improved the
      heartburn score at 4 and 8 weeks. The clinical response rates did not differ
      between roxatidine and omeprazole. Both roxatidine and omeprazole significantly
      relieved not only reflux but also abdominal pain and indigestion. The degrees of
      improvement did not differ between the two groups. CONCLUSION: Roxatidine
      relieved the symptoms of NERD patients with similar effectiveness to omeprazole.
      Therefore, roxatidine may be a good choice for NERD treatment.

PMID- 20698217
TI  - Presence of esophageal varices is a risk factor for non-hemorrhagic death of
      hepatocellular carcinoma patients treated with radiofrequency ablation.
AB  - BACKGROUND/AIMS: The presence of esophageal varices (EVs) is believed to be a
      factor that affects the prognosis of patients with hepatocellular carcinoma
      (HCC). We examined whether the presence and severity of EVs affected either
      survival prognosis or the cause of death in HCC patients treated with
      radiofrequency ablation (RFA). METHODOLOGY: The study included 89 HCC patients
      treated with RFA who were endoscopically evaluated for EVs before treatment. To
      determine factors associated with survival, we performed univariate and
      multivariate analyses of variables including demographics, tumor stage, Child
      Pugh class and status of EVs. Furthermore, we investigated the association
      between the presence of EVs and causes of death. RESULTS: Multivariate analyses
      showed both Child-Pugh class B (odds ratio: 2.654; p = 0.017) and EVs (odds
      ratio: 3.18; p = 0.004) to be independent factors of poor prognosis. Of 34
      patients who died during the period of observation, one died because of an EV
      rupture. CONCLUSIONS: The existence of EVs may affect survival prognosis of HCC
      patients treated with RFA independently of Child-Pugh status, but is not
      associated with hemorrhagic death.

PMID- 20698218
TI  - Electron microscopic studies of esophageal wall structures in patients with
      achalasia: casting more light on unresolved aspects of pathogenesis.
AB  - BACKGROUND/AIMS: Previous investigations of esophageal tissue and serum probes
      failed to identify a common etiologic agent predisposing to, triggering or
      causing achalasia. In order to further examine the detailed pathologic processes
      resulting in achalasia we performed electron-microscopic studies of muscle
      biopsies taken from the LES high pressure zone in patients undergoing surgery-
      either Heller myotomy or esophageal resection. METHODOLOGY: Smooth muscle
      biopsies with a 20 x 15-mm longitudinal segment of the myenteric plexus from the
      distal esophagus (lower border of the esophageal incision) in patients undergoing
      Heller myotomy for achalasia were taken. In patients with end-stage achalasia and
      mega-esophagus with esophageal resection, the complete esophageal body was
      available. For electron microscopy, ultrathin sections were contrasted with
      uranyl-acetate and plumbic citrate. The photographs were taken by a digitalized
      electron-microscope (ZEISS, Leo 905). RESULTS: A striking finding was the large
      number of mast cells in the region of the smooth muscle layers as well as in the
      surrounding connective tissue and also in close vicinity to the nerve cells and
      to the nerve fibres. The smooth muscle cells in these regions were very often
      stained less intensively, and they showed signs of an acute degenerative process.
      CONCLUSION: Our electron microscopic studies suggest that mast cells may play an
      important role in the secondary pathogenesis of achalasia. Esophageal retention
      and bacterial overgrowth with stasis esophagitis causing mucosal injury may be a
      mechanism of increased antigen exposure.

PMID- 20698219
TI  - Esophageal cancer associated with other primary cancers--historical comparison of
      clinicopathologic features in 359 esophageal cancer patients.
AB  - BACKGROUND/AIMS: We historically investigated the clinicopathologic features of
      esophageal cancer associated with other primary cancers (OPC), and discussed
      differences between the last decade and the previous period. METHODOLOGY: A total
      of 359 patients with esophageal cancer treated between 1981 and 2006 were
      enrolled. They were divided into 2 groups; 213 patients between 1981 and 1996
      (Group-A), and 146 patients between 1997 and 2006 (Group-B). RESULTS: Between
      Group-A and Group-B, there was a significant difference in the frequency of OPC
      (15.5% vs. 32.2%, p < 0.001). Regarding the site of OPC, there was a significant
      difference in the frequency of head and neck cancers (p < 0.001). There was a
      significant difference in the frequency of metachronous OPC between Group-A and
      Group-B (5.6% vs. 18.5%, p < 0.001). Antecedent OPC was more frequently observed
      in Group-B than Group-A (3.3% vs. 11.0%, p < 0.01), and subsequent OPC was also
      more frequently observed in Group-B than Group-A (2.8% vs. 7.5%, p < 0.05).
      Although the 5-year survival rate after esophagectomy of the patients without OPC
      was better in Group-B than Group-A (31.5 % vs. 52.7 %; p < 0.01), there was no
      difference in that of the patients with OPC between Group-A and Group-B, (40.7%
      vs. 54.2%). CONCLUSION: Metachronous as well as synchronous OPC in esophageal
      cancer patients were more frequent in the recent period than in the previous
      period. We should consider antecedent, synchronous, and subsequent OPC in
      esophageal cancer patients.

PMID- 20698220
TI  - Factors predicting incomplete endoscopic hemostasis in bleeding gastroduodenal
      ulcers.
AB  - BACKGROUND/AIMS: To investigate the factors contributing to failure of initial
      hemostasis in patients undergoing endoscopic hemostasis. METHODOLOGY: A total of
      316 patients underwent endoscopic hemostasis for bleeding peptic ulcers in a
      period of 4 years. RESULTS: For hemostatic procedures, application of hemostatic
      clips, band ligation, injection of hypertonic saline epinephrine solution, soft
      coagulation, and argon plasma coagulation were employed either singly or in
      combination. Patients were divided into the following 2 groups for multivariate
      analysis: durable hemostasis (n = 268) and failed initial (incomplete) hemostasis
      (n = 48). Hemodialysis was a risk factor of incomplete hemostasis (Odds Ratio
      [OR] = 2.306, 95% confidence interval [CI] = 1.033-5.147; p = 0.041). Compared
      with the duodenal 2nd portion, the following bleeding sites had significantly
      lower risk of incomplete hemostasis (approximately 5 times less likely): The
      duodenal bulb (D), OR = 0.215, 95% CI = 0.058-0.797 (p = 0.022); the L region, OR
      = 0.207, 95% CI = 0.046-0.919 (p = 0.038); the M region, OR = 0.132, 95% CI =
      0.036-0.482 (p = 0.002); and the U region, OR = 0.164, 95% CI = 0.041-0.649 (p =
      0.01). CONCLUSIONn: Hemodialysis and a bleeding site located in the duodenal
      second portion were the factors strongly associated with incomplete hemostasis in
      bleeding gastroduodenal ulcers.

PMID- 20698221
TI  - Can systemic cytokines predict relapse of inflammatory bowel disease?
AB  - BACKGROUND/AIMS: To determine the value of systemic cytokines as predictors of
      relapse in inflammatory bowel disease (IBD). METHODOLOGY: A prospective study
      with 135 patients in clinical remission for at least 3 months. At enrollment, a
      venous blood was drawn in order to measure, by an ELISA test, the following
      cytokines: TNFalpha, TNFalpha-R1 and R2, IL-16, IL-1beta, IL 2, IL-R2, IL-6, IL
      10, and IFNgamma. All patients were followed-up for one year. RESULT: Sixty-six
      patients had Crohn's disease (CD) and 69 had ulcerative colitis (UC). Thirty-nine
      (30%) had a relapse. Forty-four percent were receiving immunomodulatory therapy.
      No differences were found regarding detection and baseline concentration of the
      various cytokines between patients with CD and UC, or between patients with or
      without ongoing use of immunomodulators. The detection and concentration levels
      of cytokines were not associated with the risk of relapse of IBD. CONCLUSIONS:
      Systemic cytokines are of little value to predict IBD relapse.

PMID- 20698222
TI  - Surveillance culture of endoscope to monitor the quality of high-level
      disinfection of gastrointestinal reprocessing.
AB  - BACKGROUND/AIMS: Inadequate reprocessing of endoscopes or endoscopic accessories
      may result in iatrogenic infection and present a risk to public health. The aim
      of this study is to utilize microbiological cultures of endoscopes to assess the
      adequacy of standard reprocessing procedures. METHODOLOGY: A prospective study to
      randomly cultures of endoscopes and colonoscopies immediately after the
      completion of the decontamination cycle monthly. The samples were obtained by
      flushing 50 ml sterile distilled water to the internal channel and collected into
      a sterile container. These samples were incubated at 37 degrees C and examined
      for bacterial growth. RESULTS: A total of 49 cultures were obtained from June to
      December in year 2005. Three out of 7 were culture positive in the first month
      initially, but after prolonged the soaking duration to 25 minutes, the subsequent
      cultures were reduced to 1 positive sample only. The positive culture rate was
      18.4% (9/49), and 44.4% (4/9) in Monoflora culture and 55.6% (5/9) in Multi
      flora. Upper endoscopes decontaminated by automated endoscopic washing machine
      labeled as number 5 was found persistently culture positive with varied organisms
      despite vigorous manual cleaning and prolonged disinfectant soaking duration. At
      repair, the relief valve in the automated endoscopes washing machine was damaged
      and disconnected. After repair, subsequent cultures were negative. CONCLUSIONS:
      Endoscopy culturing is a useful method to assess the effectiveness of standard
      reprocessing procedures. Servicing of automated endoscope washer regularly is
      mandatory to minimize cross infection and quality assurance.

PMID- 20698223
TI  - Association between tumor necrosis factor-alpha and Fc-gamma receptor
      polymorphisms with infliximab in Crohn's disease.
AB  - BACKGROUND/AIMS: The associations between tumor necrosis factor-alpha (TNF-alpha)
      and Fcgamma receptor (FcgammaR) polymorphisms with infliximab (IFX) treatment of
      Crohn's disease (CD) are not well known. The aim of this study was to evaluate
      the association between these polymorphisms and IFX treatment of CD. METHODOLOGY:
      DNA was obtained from 41 CD patients (13 females, 28 males). TNF-alpha and
      FcgammaR polymorphisms were determined by the polymerase chain reaction-based
      restriction fragment length polymorphism method. Patients were given IFX 5 mg/kg
      intravenously and were followed prospectively for 8 weeks. The CD activity index
      (CDAI) was measured before and 8 weeks after treatment. Patients were classified
      as responders or non-responders according to the CDAI. RESULTS: The distribution
      of TNF-alpha, FcgammaRIIA, and FcgammaRIIIA genotypes was not significantly
      different between responders and non-responders 8 weeks after treatment. The
      distribution of FcgammaRIIIB genotypes significantly differed between responders
      and non-responders after 8 weeks (P < 0.05). CONCLUSIONS: FcgammaRIIIB
      polymorphisms may be an important factor for clinical response to IFX treatment
      in CD.

PMID- 20698224
TI  - Relationship between period of survival and clinicopathological characteristics
      in patients with hepatocellular carcinoma who underwent hepatectomy.
AB  - BACKGROUND/AIMS: Cancer death in the early period after hepatectomy remains
      problematic in patients with hepatocellular carcinoma (HCC). We examined the
      relationship between clinicopathological parameters' and survival periods in 234
      HCC patients who underwent hepatectomy. METHODOLOGY: Patients were divided into
      four groups: Group 1, survival > 5 years; Group 2, survival for 2-5 years; Group
      3, cancer death at 2-5 years; and Group 4, cancer death in < 2 years. RESULTS:
      Numbers of patients in each subgroup were: Group 1, n = 87 (37%); Group 2, n = 44
      (19%); Group 3, n = 46 (20%); and Group 4, n = 57 (24%). Child-Pugh B status,
      blood loss > 1500 ml, multiple tumors, tumor size > 5 cm, not meeting Milan
      criteria, irregular macroscopic findings, invasion of Glissonian pedicle,
      invasion of hepatic vein, higher modified Japan Integrated Staging score (3-5),
      long-term ascites after hepatectomy and postoperative tumor recurrence within 12
      months were frequent in Group 4 ( p < 0.05). Multivariate analysis revealed AFP
      level > or = 1000 ng/ml (hazard ratio (HR), 2.6) and early tumor relapse (HR,
      8.1) as independently related parameters ( p < 0.05). CONCLUSIONS: Careful follow
      up for early tumor relapse may be important for improving postoperative outcomes
      in HCC patients with high preoperative AFP levels.

PMID- 20698225
TI  - JAB1 expression is associated with inverse expression of p27(kip1) in
      hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: Recent studies have shown that overexpression of c-jun
      activation domain binding protein 1 (JAB1) and reduced expression of p27(kip1)
      are associated with advanced tumor stage and poor prognosis in several human
      cancers. Here, We investigated the functional role and correlation of JAB1 and
      p27(kip1) in hepatocellular carcinoma (HCC). METHODOLOGY: Immunohistochemical
      study for JAB1, p27(kip1) was performed on 76 cases of HCC and adjacent
      nontumorous tissues. 6 Fresh specimens of HCC and the adjacent liver tissue were
      collected for Western blot analysis. The influence of As2O3 on HCC SMMC-7721
      cells, was detected by flow cytometry and Hochest staining. The expression and
      subcellular localization of p27(kip1) and JAB1 were investigated by Western blot
      and immunofluorescence. RESULTS: The expression of JAB1 was higher but p27(kip1)
      was lower in HCC than that in adjacent liver tissue. As2O3 treatment inhibited
      the growth of SMMC-7721 cells. In As2O3-treated cells, p27(kip1) expression was
      increased while JAB1 was decreased. The location of p27(kip1) and JAB1 were
      transferred from cytoplasm to nucleus. CONCLUSIONS: In HCC, JAB1 was inversely
      correlated with p27(kip1). As2O3 attenuated the expression of JAB1, disturbed the
      location and expression of p27(kip1), which may participate in regulating the
      growth of human hepatoma cells.

PMID- 20698226
TI  - The clinical and histological characteristics and outcomes of drug induced
      chronic liver injury after removing causative drugs.
AB  - BACKGROUND/AIMS: To investigate characteristics and outcomes of drug induced
      chronic liver injury after removing causative drugs. METHODOLOGY: Between Apr
      2001 and Mar 2010, patients diagnosed as drug induced liver injury and with
      chronic courses, were observed. Chronic liver injury was defined as persistent
      biochemical abnormality for more than 6 months after drugs withdrawal. RESULTS:
      Forty patients were observed with mean age 41 years and female 28 (70%). Of the
      40 patients, 32 (80%) cases showed hepatocellular injury at the onset of liver
      damage, 4 (10%) cases showed cholestatic injury, and 4 (10%) cases showed mixed
      injury. Of 32 patients with hepatocellular injury, 24 (75%) cases resemble acute
      icteric hepatitis at the onset of liver damage. Of 27 patients with
      hepatocellular injury who underwent liver biopsy, 14 (51.9%) cases showed chronic
      hepatitis with a mean follow up of 17 months. Of total 40 patients, 15 (37.5%)
      patients resolved; 18 (45%) cases remained persistent liver injury, 4 (10%) cases
      developed cirrhosis, 3 (7.5%) cases died. Herbs (45.5%) are the commonest drugs
      implicated in chronic liver injury. CONCLUSIONS: Most cases with drug induced
      chronic liver injury after removing causative drugs resemble acute icteric
      hepatitis at the onset of liver damage. Some patients can resolve, some may
      progress to cirrhosis. Herbs are important drugs for drug induced chronic liver
      injury.

PMID- 20698227
TI  - Can angiogenesis be a target of treatment for ribavirin associated hemolytic
      anemia?
AB  - BACKGROUND/AIMS: Recently ribavirin has been found to inhibit angiogenesis and a
      number of angiogenesis inhibitors such as sunitinib and sorafenib have been found
      to cause acute hemolysis. We aimed to investigate whether there is a relation
      between hemoglobin, haptoglobin and angiogenesis soluble markers which are
      modifiable and can help in developing strategies against anemia. METHODS:
      Fourteen patients chronically infected with hepatitis C virus were treated by
      pegylated interferon alpha 2a and ribavirin. Serum hemoglobin, haptoglobin and
      angiogenesis markers of vascular endothelial growth factor and angiopoetin-2 were
      investigated before and after therapy. RESULTS: We observed a significant
      decrease in haptoglobin levels at the end of the treatment period. Hemoglobin
      levels also decreased but insignificantly by treatment. In contrast with the
      literature, serum levels of angiogenesis factors did not change significantly by
      pegylated interferon and ribavirin therapy. We found no correlation of
      angiogenesis soluble markers with either hemoglobin or haptoglobin. CONCLUSION:
      This is the first study in the literature investigating a link between
      angiogenesis soluble markers and ribavirin induced anemia in patients with
      hepatitis C and we could not find any relation. Future research with larger
      number of patients is needed to find out modifiable factors that will improve the
      safety of ribavirin therapy.

PMID- 20698228
TI  - Recurrence of hepatocellular carcinoma after liver transplantation: recurrence
      characteristics and risk factors.
AB  - BACKGROUND/AIMS: The aim of this study was to investigate tumor recurrence
      characteristics of hepatocellular carcinoma (HCC) after liver transplantation
      (LT), including recurrence sites, time and risk factors, and to provide a basis
      for predicting and preventing tumor recurrence. METHODOLOGY: Data from 224
      consecutive patients with HCC who underwent LT between Feb 1999 and December 2008
      at our center had been retrospectively analyzed. Tumor-unrelated, perioperative
      and in hospital deaths were excluded (n = 39). All the cases were followed-up
      regularly. According to recurrence or not, the cases were divided into recurrence
      group (n = 103) and non-recurrence group (n = 99). The data were analyzed
      statistically. RESULTS: Extrahepatic and single site recurrences were more common
      in early postoperative days, especially in the lung. No significant relation was
      observed between recurrence sites and time. Exceeding Milan criteria (MC),
      macrovascular invasion, liver capsule invasion, satellite lesions and Tumor-Node
      Metastasis (TNM) classification of UICC were observed significant different in
      univariate analysis. TNM classification and macrovascular invasion were
      considered 2 independent risk factors in multivariate analysis. Macrovascular
      invasion was a independent risk factor for very early recurrences (6 months).
      CONCLUSIONS: Recurrence of HCC after LT was not frequent at intrahepatic but
      extrahepatic sites. The recurrence time was mainly in early operative days. TNM
      classification and macrovascular invasion are risk factors. Macrovascular
      invasion is associated with early recurrence.

PMID- 20698229
TI  - Zhixue capsule caused seven cases of drug induced hepatitis.
AB  - BACKGROUND/AIMS: To report the recently 7 cases of drug induced hepatitis
      patients in our department. METHODOLOGY: From October 2008 to December 2008, 7
      patients were enrolled in our department for drug induced hepatitis caused by
      Zhixue capsules administration. The Zhixue capsule is composed of cortex dictam
      and radices sophorae flavescentis. There were 4 female and 3 male patients. The
      patients were of age 31 to 52 years old. Of those, 6 patients belonged to the
      hepatocellular injury type and one to the mixed type. The time period Zhixue
      capsule was administered was from 6 to 18 days. When the patients enrolled into
      our department, they were treated for jaundice and protective liver function.
      RESULTS: When the patients were discharged the symptoms were all improved
      evidently and liver function became normal. One patient with mixed type was
      hospitalized for 63 days and he was treated with glucocorticoid to help his
      recovery. CONCLUSIONS: Zhixue capsule could induce acute hepatitis of various
      types, but mainly hepatocellular injury type. The patients of all types could be
      recovered with proper treatment. The combined type may need glucocorticoid
      administration to help recovery.

PMID- 20698230
TI  - Efficacy of fractionated plasma separation and adsorption system (Prometheus) for
      treatment of liver failure due to mushroom poisoning.
AB  - BACKGROUND/AIMS: Consuming wild mushrooms is an ordinary habit in late summer and
      autumn in our region. Every year, several cases of hepatic toxicity secondary to
      mushroom poisoning are observed because of poor identification of the mushrooms.
      Unfortunately some of them are fatal. Prometheus system is a newly developed
      extracorporeal liver support device for fractionated plasma separation and
      adsorption (FPSA) that enables removal of albumin-bound and water-soluble toxins.
      Therefore, it may be a promising treatment option for patients with liver failure
      due to mushroom poisoning. METHODOLOGY: We studied 8 patients with mushroom
      poisoning. All patients underwent 1 to 4 consecutive FPSA (Prometheus)-system in
      addition to medical and supportive treatment such as fluid replacement,
      Penicillin G, N-acetylcysteine (NAC) and silymarin. A variety of clinical and
      biochemical parameters were assessed. RESULTS: We had improvement of the
      biochemical parameters after first treatment with FPSA-system. Seven of 8
      patients survived and were discharged to resume an independent life. One patient
      who had grade III encephalopathy when admitted to hospital died. No major adverse
      events were observed during the application of this therapy modality.
      CONCLUSIONS: FPSA-system may be a safe and effective treatment option for patient
      with mushroom poisoning. Early hospitalization is essential in order to be
      successful. Controlled studies are needed to evaluate the efficacy of this new
      treatment choice on survival of patients with acute liver failure (ALF) due to
      mushroom poisoning.

PMID- 20698231
TI  - Cloning of a fusion gene containing hGM-CSF gene and gene encoding L protein of
      HBV and expression in Pichia Pastoris.
AB  - BACKGROUND/AIMS: To construct the yeast expression vector containing cDNA
      sequence coding L protein of Hepatitis B Virus (HBV) and human granulocyte
      macrophage colony stimulating factor (hGM-CSF), and to explore the method of
      secretory expression in Pichia Pastoris GS115 strain. METHODS: We used pVAX1-L
      hGM as template to amplify L-hGM gene by PCR, and then the PCR products were
      cloned into the yeast expression vector pPICZaC with DNA recombination method.
      After linearized by Sac I, the recombinant plasmid pPICZa C-L-hGM was transformed
      into Pichia Pastoris GS115 by electrophoresis. The expressing protein was induced
      by methanol. SDS-PAGE and Western blot were used to analyze the expression of
      protein. RESULTS: DNA sequence analysis revealed that the constructed genes
      sequences were totally consistent with the GeneBank reported. The results of SDS
      PAGE and Western blot showed that the recombinant protein was induced by methanol
      and stably expressed in Pichia Pastoris. CONCLUSIONS: The successful construction
      of a recombinant yeast expression vector containing gene coding L protein of
      Hepatitis B virus and hGM-CSF gene, and expressed in Pichia Pastoris, of which
      lays a foundation for the further researches on a better protective HB vaccine.

PMID- 20698232
TI  - Prospective randomized controlled study of short-term perioperative oral
      nutrition with branched chain amino acids in patients undergoing liver surgery.
AB  - BACKGROUND/AIMS: Early prospective randomized clinical trials demonstrated that
      perioperative parenteral nutrition (PN) with branched chain amino acids (BCAA) is
      beneficial in cirrhotic patients with hepatocellular carcinoma who undergo
      hepatectomy. However, PN support is expensive and requires a long hospital stay.
      Moreover, PN support has not been evaluated in patients with a normal liver who
      undergo hepatectomy. It was studied the benefits of perioperative oral nutrition
      (ON) with BCAA in patients who underwent hepatectomy, including those with a non
      hepatitis liver. METHODOLOGY: In this prospective, randomized, controlled trial,
      38 patients were assessed for eligibility. Fourteen patients were excluded
      because they had received intraoperative blood transfusions or incomplete
      resections. The 24 eligible patients (20 with malignant liver tumors and 4 with
      benign liver tumors) were randomly assigned to receive perioperative ON with BCAA
      (11 patients, BCAA group) or a usual diet (13 patients, control group). The BCAA
      group received a BCAA supplement twice daily plus a usual diet for 14 days before
      operation and on days 1 to 7 after operation. The control group received a usual
      diet alone. The primary end point was the improvement in postoperative
      biochemical measurements. RESULTS: Two of the 11 patients in the BCAA group
      developed postoperative complications, as compared with 3 of the 13 patients in
      the control group (18.2% vs. 23.1%, p = 0.7686). Serum levels of alanine
      aminotransferase, aspartate aminotransferase, and ammonia did not differ
      significantly between the BCAA group and control group; however, peak values were
      lower in the BCAA group. There was no difference between the groups in serum
      hemoglobin levels after operation. Among patients with hepatitis, serum
      erythropoietin (EPO) levels on POD 3, 5, and 7 were slightly but not
      significantly higher in the BCAA group than in the control group. Among patients
      with non-hepatitis, serum EPO levels on POD 3, 5, and 7 were significantly higher
      in the BCAA group than in the control group (p = 0.0174, p = 0.0141, and p =
      0.0328, respectively). CONCLUSION: Short-term ON support with BCAA was associated
      with higher serum EPO levels than was a normal diet in patients with non
      hepatitis who underwent curative hepatic resection. Higher EPO levels might be
      beneficial in protecting liver cells from ischemic injury and preventing
      intraoperative hemorrhage associated with lower perioperative levels of alanine
      aminotransferase and aspartate aminotransferase in serum. This is the first study
      to demonstrate an effect of EN support with BCAA in patients with non-hepatitis,
      as well as those with hepatitis.

PMID- 20698233
TI  - Predicting dry weight in patients with ascites and liver cirrhosis using computed
      tomography imaging.
AB  - BACKGROUND/AIMS: In cirrhotic patients, ascites may increase weight and adversely
      impact liver transplant candidacy. METHODOLOGY: In this study we used linear and
      volume measurements from abdominal CT imaging to estimate dry weight of
      transplant candidates using multivariable linear regressions. We reviewed 200
      scans. For males there were 81, 26, and 41 scans with no/small, moderate, and
      large ascites, respectively, and 41, 6, and 5 scans of females with
      no/small/moderate, and large ascites respectively. RESULTS: In males without
      ascites, subxiphoid subcutaneous fat volume had the strongest correlation with
      weight (r = 0.826); the best prediction utilized four variables including height,
      subcutaneous subxiphoid fat volume, and intraabdominal and subcutaneous umbilicus
      fat volumes (r = 0.923, r2 = 0.852, SEE = 15.15, p < 0.001). In females,
      subcutaneous fat volume above the umbilicus had the best correlation (r = 0.815);
      incorporating height and anterior subxiphoid fat thickness increased predictive
      accuracy (r = 0.892, r2 = 0.796, SEE = 15.37, p < 0.001). These regressions
      consistently under-predicted scale weight in patients with moderate and large
      ascites (5.92 +/- 25.50 pounds and 11.21 +/- 19.34 pounds in males, and 2.29 +/-
      23.76 and 8.37 +/- 11.44 in females). CONCLUSIONS: Equations to estimate patient
      weight regardless of ascites may offer a more accurate representation of size
      than scale weight in transplant candidates with ascites.

PMID- 20698234
TI  - Safety evaluation of donors when performing modified extended right lobe
      hepatectomy in ALDLT.
AB  - BACKGROUND/AIMS: To evaluate the safety of the donor after donation of right lobe
      with middle hepatic vein (MHV) in adult-to-adult living donor liver
      transplantation (ALDLT). METHODOLOGY: From Jun 2006 to Dec 2008, 32 patients
      underwent ALDLT using right lobe liver grafts in our center according to our own
      individualized selection criteria of the right lobe graft with MHV, in which 22
      donors received right lobe graft without MHV (Group 1, n = 22) and 10 donors
      received right lobe graft with MHV (Group 2, n = 10). Besides protecting the
      venous return of segment IVb, we reserved the tissue of segment IV as much as
      possible. We compared the two groups in terms of their intraoperative data,
      postoperative recovery, complication, regeneration of the remnant liver and
      spleen hypersplenism. RESULTS: There was no significant difference between two
      groups in ages, steatosis of the graft, remnant liver volume, etc., nor the
      operation time and blood loss. Besides the body weights and whole-liver volumes
      which were greater in group 1 than in group 2, the graft weights (GW) were
      proximate in two groups, and there were no significant differences in GW/SLV and
      GRWR as well. Donors in both group 1 and group 2 recovered with satisfaction, and
      the serum ALT from group 2 recovers even faster than that from group 1; Three
      months after operations, the remnant livers from group 2 appeared to have a good
      regeneration as well as the spleen, though there was only one case developing
      temporary hypersplenism. There was no statistical difference in the rate of
      complications (p = 0.79). CONCLUSION: It is more accessible to obtain a larger
      graft with modified extended right lobe hepatectomy. Congestion in segment IV
      might help the remnant liver to regenerate. For donors with more than 35% livers
      reserved without obvious hepatic steatosis, it is safe to perform right lobe
      hepatectomy with MHV.

PMID- 20698235
TI  - Orthotopic liver transplantation for cholestatic diseases.
AB  - BACKGROUND/AIMS: According to the data of the European Liver Transplant Registry
      (ELTR), liver transplantations (LTx) as a result of bile duct diseases were
      reported in 12.0% of cases. The aim of this study was to overview retrospective
      indications for operation and results of patients who underwent LTx for
      cholestatic diseases. METHODOLOGY: 725 LTx were performed between January 1989 to
      December 2008, including 173 (23.9%) patients with cholestatic diseases. 80 pts
      (46.2%) were operated because of PBC, 63 pts (36.4%) with PSC and 12 pts (6.9%)
      with SBC as a result of iatrogenic bile ducts injuries. In 6 pts (3.5%) Caroli's
      disease was the reason for transplantation and another 11 pts (6.4%) were
      operated because of infiltration of alveococcosis into the bile duct.
      Cholangiocarcinoma (CCC) developed in 6 pts with PSC (9.5%) undergoing LTx. The
      last patient (0.6%) of our group was operated because of mucoviscidosis. 24 pts
      (13.9%) underwent unsuccessful surgical treatment prior to the LTx. RESULTS: 142
      pts (82.1%) presented good outcome, but complications in postoperative period
      were present in 31 pts (17.9%). 8 pts (4.6%) required re-laparotomy: 6 pts due to
      intraperitoneal bleeding and hematoma in the first postoperative week and 2 pts
      due to liver abscess, 1 month and 3 months after LTx respectivelly. 4 patients
      (2.3%) died in the first week after LTx (septic complications, acute rejection).
      5 patients with CCC died in the period of 7 to 26 months after LTx. This was
      caused by the recurrence of the cancer. The overall mortality was 8.1% (14 pts).
      4 pts (2.3%) underwent ReLTx due to various origins--one case due to hepatic
      artery thrombosis, another was ischemic type biliary lesion (ITBL) and two
      patients due to recurrence of PBC and PSC. Cumulative 1, 5 and 10 year recurrence
      free survival rates after LTx were: 94.6% / 88.7% / 72.1% in PBC group, 95.3% /
      86.5% / 70.2% in PSC group and 73.9% / 69.2% / 59.3% in SBC group of patients.
      CONCLUSION: There is no doubt that LTx is a good and effective option of
      treatment for patients with cholestatic diseases. Nevertheless the long-term
      benefits of LTx depend on precise indications and timing of the operation.

PMID- 20698236
TI  - Clinical significance of intracapsular and extratumoral venous invasion in
      hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: The current study sought to clarify whether intracapsular venous
      invasion and extratumoral venous invasion confer different prognostic
      significance in patients undergoing hepatectomy for hepatocellular carcinoma.
      METHODOLOGY: A retrospective study of 275 consecutive patients who underwent
      hepatectomy for hepatocellular carcinoma was conducted. Extratumoral venous
      invasion was defined as gross or microscopic involvement of vessels within the
      peritumoral liver tissue, whereas intracapsular venous invasion was defined as
      microscopic involvement of vessels within the fibrous tumor capsule. The median
      follow-up time was 64 months. RESULTS: Vascular invasion was found in 104 (38%)
      of the 275 patients. Intracapsular venous invasion was present in 16 patients and
      extratumoral venous invasion observed in 88 patients. Overall cumulative survival
      rates were 64% at 5 years and 45% at 10 years. Vascular invasion was a strong
      prognostic factor by univariate (p = 0.0001) and multivariate (p = 0.006)
      analyses. Survival after hepatectomy was significantly worse in patients with
      extratumoral venous invasion (cumulative 10-year survival rate of 28%) than in
      patients with intracapsular venous invasion (cumulative 10-year survival rate of
      70%; p = 0.0082). CONCLUSIONS: Extratumoral venous invasion adversely influences
      survival after hepatectomy for hepatocellular carcinoma compared to intracapsular
      venous invasion.

PMID- 20698237
TI  - Emergency embolization in the treatment of ruptured hepatocellular carcinoma
      following transcatheter arterial chemoembolization.
AB  - BACKGROUND/AIMS: Rupture of hepatocellular carcinoma (HCC) following
      transcatheter arterial chemoembolization (TACE) is a rare and life-threatening
      complication. The purpose of the present study was to evaluate the utility of
      emergency embolization for treatment of ruptured HCC following TACE. METHODOLOGY:
      Five patients developed rupture of tumor after TACE in 1005 patients of HCC from
      October 2007 to February 2010, and were studied retrospectively. Emergency
      selective arterial embolization was performed in all 5 patients because of
      intractable hemorrhage in the peritoneal cavity or around the liver that could
      not be controlled by conservative method. The mean hemoglobin level before
      embolization was 75.6 g/L +/- 20.7 (mean +/- standard deviation). RESULTS:
      Hepatic angiography did not revealed extravasation of contrast from the tumor in
      all 5 patients with rupture of HCC following TACE. After selective embolization
      of feeding arteries of the liver tumor, intraperitoneal bleeding from HCC was
      stopped immediately in all patients. The mean hemoglobin level after embolization
      in 48 hours was 102.6 g/L +/- 3.5. No severe complication related to emergency
      embolization was found after treatment. CONCLUSIONS: Emergency arterial
      embolization is effective for hemostasis of ruptured HCC following TACE in
      patients with hemodynamically unstable condition.

PMID- 20698238
TI  - The peculiar processing of pancreatic hormone glucagon seen in traumatized
      patients.
AB  - BACKGROUND/AIM: The kinetics of the pancreatic hormone glucagon in traumatized
      patients has not been minutely investigated as well as that of insulin, despite
      its significant influence on energy metabolism. In the present study, we examined
      the kinetics of glucagon and glucagon-related peptides assessed by
      radioimmunoassay, and the molecular forms of these peptides using gel filtration
      chromatography. In addition, we discuss glucagon processes in the pancreas and
      intestine in traumatized patients in the early operative days. METHODOLOGY:
      Twelve traumatized patients who had undergone emergency surgery were enrolled in
      this study (group S). Ten healthy volunteers were also enrolled as normal control
      subjects (group C). The serum level of glucagon and glucagon-related peptides
      were assessed in the early morning fasting state in both groups, on the second
      postoperative day in group S, using the glucagon nonspecific N-terminal (glucagon
      like immunoreactivity [GLI]) and specific C-terminal (immunoreactive glucagon
      [IRG]) radioimmunoassays. The molecular forms of these peptides were also
      estimated using the gel filtration chromatography method. RESULTS: Serum IRG in
      group S was significantly high compared with that of group C (P < .05). Serum GLI
      was not significantly different between both groups. In all 12 patients in group
      S, a peculiar glicentin-like peptide (GLLP: MW approximately 8000 Da) other than
      pancreatic glucagon was seen on gel filtration chromatography, which was not seen
      in group C. CONCLUSIONS: The kinetics and processing of glucagon in traumatized
      patients was different from those of healthy subjects. In traumatized patients,
      the peculiar processing of glucagon was processed in the intestine, which is
      different from the ordinary glucagon processing either in the pancreas or the
      intestine, generating a peculiar glicentin-like peptide (GLLP).

PMID- 20698239
TI  - Negative pressure external drainage of the pancreatic duct in
      pancreaticoduodenectomy.
AB  - BACKGROUND/AIMS: Despite the development of surgical techniques, postoperative
      pancreatic fistula is still one of the main causes of serious morbidity after
      pancreaticoduodenectomy. Nevertheless numerous studies have been done, studies on
      preventing pancreatic fistula are lacking. This study is focused on the
      effectiveness of negative pressure external drainage for pancreaticojejunostomy
      in pancreaticoduodenectomy patients. METHODOLOGY: Seventy-six patients were
      scheduled for pancreaticoduodenectomy at Soonchunhyang University Hospital from
      January of 2003 to August of 2007. Negative suction drainage group (n = 41) and
      no negative suction drainage group (n = 35) were compared by patient
      characteristics, parameters related to operation, and complications. RESULTS:
      There were no statistical differences between both groups in patient demographics
      and parameters related to operation. The complication rates were significantly
      lower in negative suction drainage group in terms of postoperative bleeding (P =
      0.012), choledochojejunostomy leak (P = 0.014), and pancreatic fistula (P =
      0.018). CONCLUSIONS: This retrospective study showed that external stenting with
      negative pressure suction drainage of the pancreatic duct has significantly
      reduced the rate of pancreatic fistula in duct-to-mucosa pancreaticojejunostomy
      with improved surgical outcomes.

PMID- 20698240
TI  - Outcome of pseudocysts complicating chronic pancreatitis.
AB  - BACKGROUND/AIMS: Pancreatic pseudocysts are frequent complication of chronic
      pancreatitis with incidence rate from 20 to 40%. The aim of our study was to
      establish a possible correlation between clinical features and outcome of
      pseudocysts complicating chronic pancreatitis. METHODOLOGY: We included in the
      study 37 patients with chronic pancreatitis and pancreatic pseudocysts treated at
      the Department of Digestive Tract Diseases of Lodz Medical University between
      2003-2008. For each patients the following parameters were recorded: number and
      location of pseudocysts, diameter, kind of treatment, recurrence rate and time of
      hospitalisation. RESULTS: The mean size of pancreatic pseudocysts was 7.8 cm
      (range 2-16 cm). Spontaneous regression was observed in 7 pseudocysts (18.9%),
      persistence without symptoms and without size enlargement in 9 patients (24.3%).
      Twenty one (56.8%) pseudocysts required therapeutic intervention: endoscopic
      procedures (27.1%), surgical treatment (18,.9%) or percutaneous drainage (10.8%).
      Mean pseudocyst size for conservative treated patients was 4.2 compared to 9.6
      for patients with interventional treatment (p < 0.05). The overall recurrence
      rate was 33.3%. The mean hospital stay of patients treated endoscopically was
      significantly shorter than those treated surgically (p < 0.01) and shorter than
      those of percutaneous drainage (p < 0.01). CONCLUSION: Pseudocysts treatment in
      chronic pancreatitis may be effectively achieved by both endoscopic and surgical
      means. Nonetheless, the endoscopic drainage, with lower hospitalization period,
      should be considered for initial therapy in each appropriate patients.

PMID- 20698242
TI  - The association of pre-treatment peripheral blood markers with survival in
      patients with pancreatic cancer.
AB  - BACKGROUND/AIMS: The aim of the study is to assess the prognostic value of
      pretreatment lymphocyte, neutrophil, platelet counts, mean platelet volume (MPV),
      platelet to lymphocyte ratio (PLR) and neutrophil to lymphocyte ratio (NLR) in
      patients with pancreatic cancer. METHODOLOGY: A total of 65 eligible patients
      were included in the study and retrospectively reviewed. Pre-treatment
      hematological parameters (platelet, lymphocyte, neutrophil counts, and mean
      platelet volume) and tumor marker (CA 19-9) levels were recorded. NLR was
      calculated by dividing the neutrophil count value by the number of lymphocytes.
      PLR was also calculated in a similar manner by dividing the platelet count value
      by the number of lymphocytes. RESULTS: One-year survival was 22.3% and the median
      survival time was 7 months (95% CI, 5.7-8.2) in the study group. Patients with a
      NLR value of < 5 had a significantly higher median survival duration compared to
      those with a NLR value of > or = 5 (p = 0.015). All other hematological variables
      were not significantly different. CONCLUSIONS: In patients with pancreatic
      cancer, pretreatment NLR may be use as a prognostic factor in pancreatic cancer
      patients. Further studies with larger patient cohorts are warranted to to better
      clarify the prognostic value of pre-treatment peripheral blood counts in patients
      with cancer.

PMID- 20698241
TI  - Intraductal papillary mucinous neoplasms of the pancreas--predictors of
      malignancy.
AB  - BACKGROUND/AIMS: Preoperative determination of malignancy in Intraductal
      Papillary Mucinous Neoplasms (IPMN) remains problematic. The aim of this study
      was to review our experience with surgical resection for IPMN and to identify the
      clinicopathological features that predicted malignancy in IPMN. METHODOLOGY:
      Forty patients who underwent pancreatic resection for IPMN at a single tertiary
      center between January 1996 and March 2008 were retrospectively analyzed.
      RESULTS: Thirteen patients (32.5%) had adenomas, 4 (10%) borderline IPMN, 18
      (45%) carcinoma in situ, and 5 (12.5%) invasive carcinoma. Patients with benign
      IPMN had 1-, 3-, and 5-year overall survival rates of 100%, 94.1%, and 88.2%,
      respectively and 1-, 3-, and 5-year disease-free survival rates of 100%, 94.1%,
      and 88.2%, respectively. Patients with malignant IPMN had 1-, 3-, and 5-year
      overall survival rates of 100%, 65.2%, and 56.5%, respectively and 1-, 3-, and 5
      year disease-free survival rates of 91.3%, 47.8%, and 43.5% respectively. After a
      median follow-up of 39 months (range, 9 - 89) months, there were 5 patients with
      disease recurrences (12.5%) in patients with IPMN with invasive carcinoma after
      operation. Abdominal pain, jaundice, main-duct or mixed type, tumor size, mural
      nodule and size of mural nodule, were predictive of malignant IPMN by univariate
      analysis, and size of mural nodule was identified as the only independent
      predictive factor for malignancy. CONCLUSIONS: The optimal management of IPMN
      remains controversial and should be individualized based on the balance between
      risk and benefit.

PMID- 20698243
TI  - Significance analysis of histologic type and perineural invasion as prognostic
      factors after curative resection of ampulla of Vater carcinoma.
AB  - BACKGROUND/AIMS: Periampullary adenocarcinoma has either intestinal- or
      pancreatobiliary-type of differentiation. These types and perineural invasion
      have been shown to have prognostic relevance. The influences of histologic type
      and perineural invasion on recurrence and survival in ampullar of Vater carcinoma
      still need to be assessed. METHODOLOGY: We reviewed and analyzed the
      clinicopathologic data, surgical outcomes, recurrence and survival of 49 patients
      who received curative pancreatoduodenectomy for ampulla of Vater carcinoma at
      Hanyang University Hospital between July 1994 and June 2008. RESULTS: Twenty
      patients experienced recurrence, and the 5-year overall survival rates were
      53.1%. Perineural invasion as well as tumor grade, T stage, lymph node
      metastasis, and lymphatic invasion were associated with survival (p < 0.05). The
      group positive for perineural invasion had a high recurrence rate (56.5% versus
      28.0%) and a low 5-year survival (39.1% versus 68.0%) compared to those of the
      negative group. Pancreatobililary-type had a higher recurrence rate (58.3% versus
      36.1%) and a lower 5-year survival rate (33.3% versus 61.1%) in comparison to
      intestinal-type. However, histologic type was not a statistically significant
      factor (p > 0.1). CONCLUSIONS: Perineural invasion is a significant factor for
      survival. Histologic type has no significance as a prognostic factor despite
      differences between the two subgroups.

PMID- 20698244
TI  - Dissecting the stress activating signaling pathways in acute pancreatitis.
AB  - BACKGROUND/AIMS: Acute pancreatitis is a severe and frequently a life-threatening
      disease which can lead to pancreatic necrosis, acute lung injury, SIRS and MODS.
      The pathophysiologic pattern of acute pancreatitis is being investigated, when
      guidelines for treatment are being modified often and novel therapeutic
      strategies have failed to show real benefit in clinical practice. METHODOLOGY:
      The present paper reviews the role of nuclear factors NF-kappaB and AP-1,
      TNFalpha, and TLR-4 in acute pancreatitis. CONCLUSION: Understanding the
      inflammatory mediators expression, regulation of apoptosis and dissecting the
      stress activating signaling pathways in acute pancreatitis, is of paramount
      importance in order to achieve in the near future adequate therapeutic
      interventions.

PMID- 20698245
TI  - In vitro chemosensitivity of gastric adenocarcinomas to histone deacetylase
      inhibitors, compared to established drugs.
AB  - BACKGROUND/AIMS: This study was performed to determine the efficacy of histone
      deacetylase inhibitors in gastric cancer, together with other established
      regimens. METHODOLOGY: The chemosensitivities of 93 gastric cancer patients to
      established drugs, and three histone deacetylase inhibitors (SAHA, PXD101, and a
      novel candidate, CG-2) were evaluated using the histoculture drug response assay.
      RESULTS: Tumor growth inhibition rates were the highest with cisplatin, followed
      by PXD101, taxol, docetaxel, and TS-1, in descending order. The response rates
      were 41.9-68.8%, and 37.6-47.3%, respectively, at an inhibition rate cutoff value
      of 30%. Synergistic activity was evident with most combinations of established
      drugs and histone deacetylase inhibitors. Diffuse- or mixed-type carcinomas on
      Lauren classification were closely associated with increased chemosensitivity to
      TS-1 (p = 0.044). Node-positive and "other than tubular type" tumors on WHO
      classification were chemosensitive to cisplatin (p = 0.011 and 0.014,
      respectively). CG-2 chemosensitivity was markedly associated with low
      preoperative CA724 level (< or = 4 U/ml) (p = 0.046). CONCLUSIONS: This in vitro
      chemosensitivity assay validates the comparable chemo-response of gastric cancers
      to histone deacetylase inhibitors and established drugs, indicating considerable
      therapeutic efficacy of these agents. Additionally, a number of
      clinicopathological parameters are significantly associated with specific
      regimens.

PMID- 20698246
TI  - Postoperative recurrence in gastric cancer: analysis of 59 cases.
AB  - BACKGROUND/AIMS: Gastric cancer (GC) is the leading cause of death in China.
      Although surgery based comprehensive treatment is the best approach to improve
      survival, postoperative recurrence is a major problem. This study was aimed to
      find out the relationship of cancer recurrence with major clinico-pathological
      factors, with special attention focused on time of recurrence. METHODOLOGY: Data
      of 59 recurrences after surgery among 286 GC patients were systemically collected
      and analyzed. Time of recurrence, the relationship between clinical stages and
      time of recurrence, and between number of adjuvant chemotherapy cycles and time
      of recurrence were evaluated. RESULTS: 76.3% (45/59) recurrence happened within 1
      year after surgery. Median time to recurrence was 7 months. Most recurrences were
      locoregional recurrence (57.6%). The differences in time of recurrence among
      stage I, stage II, stage III and stage IV were statistically not significant (p >
      0.05, Kruskal-Wallis Test). There were significant differences among different
      adjuvant chemotherapy cycles for time to recurrence (p = 0.014, Kruskal-Wallis
      Test). CONCLUSION: Close monitoring and active followup of patients with GC
      should be conducted over the first 2 years after operation. Adjuvant chemotherapy
      could prolong recurrence-free survival.

PMID- 20698247
TI  - Gastric mucosal cancer smaller than 7mm can be treated with conventional
      endoscopic mucosal resection as effectively as with endoscopic submucosal
      dissection.
AB  - BACKGROUND/AIMS: Recently, endoscopic submucosal dissection (ESD) has been
      accepted for the treatment of gastrointestinal mucosal neoplasms because of the
      higher en bloc resection rate. However, ESD is technically more difficult,
      requires a longer procedure time and has more frequent complications compared
      with conventional endoscopic mucosal resection (EMR). We evaluated
      retrospectively the clinical outcomes of ESD compared with EMR to determine the
      size of the lesion for choosing EMR rather than ESD. METHODOLOGY: Three hundred
      and sixty-five lesions of early gastric cancer were treated endoscopically (146
      by EMR and 219 by ESD). We compared en bloc resection, residual tumor and
      recurrence-free rates between EMR and ESD. RESULTS: En bloc resection rate was
      significantly higher with ESD (88.5%) than EMR (45.2%). With regard to lesions <
      or = 7mm in size, en bloc resection, residual tumor and recurrence-free rates did
      not differ. CONCLUSIONS: Gastric mucosal cancer < or = 7mm can be treated with
      EMR as effectively as with ESD.

PMID- 20698248
TI  - Prognostic value of preoperative CEA and CA 19-9 levels in resectable gastric
      cancer.
AB  - BACKGROUND/AIMS: Preoperative tumor marker assays have been used to predict the
      prognosis of gastric cancer, but the exact role they may play is still unclear.
      The aim of this study was to evaluate the clinical significance of preoperative
      serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 levels in
      resectable gastric cancer patients. METHODOLOGY: Seventy-five resectable,
      nonmetastatic gastric cancer patients were analysed in regard to their
      clinicopathological characteristics and their relation with tumor markers and
      influence on survival have been evaluated. RESULTS: Twenty-eight patients were
      female and 47 were male. The mean age was 61 years (range 21-85 years). Fifty-two
      patients had total gastrectomy, and 23 had a subtotal gastrectomy with D2 lymph
      node dissection. The median follow up period was 24 months (6-74 months).
      Elevated serum CA 19-9 levels correlated well with lymph node metastasis (p =
      0.008), stage (p = 0.012), vascular invasion (p = 0.03) and tumor size (p =
      0.001). The survival of the patients were not correlated with the tumor markers
      (p > 0.05). CONCLUSIONS: Elevated CA 19-9 levels are significantly correlated
      with lymph node metastasis, which may improve the selection of patients with
      advanced disease. CEA and CA 19-9 levels do not provide any predictive
      information about survival of operable, nonmetastatic gastric cancer patients.

PMID- 20698250
TI  - [Review of ecotoxicity and mechanism of engineered nanoparticles to aquatic
      organisms].
AB  - With the rapid development of nanotechnology and widespread use of nanoproducts,
      ecotoxicity of engineered nanoparticles (NPs) attracts increasing attention and
      research. This paper reviews the ecotoxicity and mechanisms of NPs to aquatic
      organisms systematically. Toxic effects of different classes of NPs to bacteria,
      algae, invertebrates and fish in aquatic environments were firstly summarized,
      possible toxicity mechanisms were then expounded and the relationship between
      toxicity mechanisms and unique physicochemical properties of NPs was also
      analyzed. The processes of NPs uptake and membrane penetration at the cell and
      molecular level were discussed and presented. In the natural water, NPs behaviors
      are influenced by water chemistry conditions, so toxic effect to aquatic
      organisms is different from that in laboratory conditions, which should be paid
      with increased attention and effort. Finally, bottle-necks and challenges of NPs
      ecotoxicity research and existing problems of test and analytical methods were
      analyzed and the future directions of research were suggested.

PMID- 20698249
TI  - Basal protrusion of ulcers induced by endoscopic submucosal dissection (ESD)
      during treatment with proton pump inhibitors, and the suppressive effects of
      polaprezinc.
AB  - BACKGROUND/AIMS: When a peptic ulcer is treated with proton pump inhibitors
      (PPI), protrusion of the ulcer base is sometimes noted during ulcer healing. To
      clarify the incidence of ulcer base protrusion in ulcers induced by endoscopic
      submucosal dissection (ESD), and whether the addition of polaprezinc, a
      cytoprotective agent used for treatment of gastric ulcer, to the PPI regimen
      helps to suppress it. METHODOLOGY: One hundred sixty-three patients on which ESD
      was performed were randomly allocated to either two groups: one treated with
      lansoprazole (30mg/day) and the other with lansoprazole (30mg/day) plus
      polaprezinc (150mg/day) for the treatment of ESD-induced ulcer. The condition of
      the ESD-induced ulcer was blindly assessed two months after ESD by two
      physicians. RESULTS: Lansoprazole plus polaprezinc group showed significantly
      better ulcer healing (p < 0.0001) and protrusion of the ulcer base was recognized
      in only 1.3% (1/77), an incidence significantly lower than that in lansoprazole
      group (20.7%, 16/77, p = 0.0001). Polaprezinc was the only significant factor (p
      = 0.0001) differentiating patients who had ulcer base protrusion (n = 17) from
      those who did not (n = 137). CONCLUSIONS: Polaprezinc prevents protrusion of the
      ulcer base during the healing of ESD-induced ulcer with PPI.

PMID- 20698251
TI  - [Resolving excitation emission matrix spectroscopy of estuarine CDOM with
      parallel factor analysis and its application in organic pollution monitoring].
AB  - The distribution and estuarine behavior of fluorescent components of chromophoric
      dissolved organic matter (CDOM) from Jiulong Estuary were determined by
      fluorescence excitation emission matrix spectroscopy (EEMs) combined with
      parallel factor analysis (PARAFAC). The feasibility of these components as
      tracers for organic pollution in estuarine environments was also evaluated. Four
      separate fluorescent components were identified by PARAFAC, including three humic
      like components (C1: 240, 310/382 nm; C2: 230, 250, 340/422 nm; C4: 260, 390/482
      nm) and one protein-like components (C3: 225, 275/342 nm). These results
      indicated that UV humic-like peak A area designated by traditional "peak-picking
      method" was not a single peak but actually a combination of several fluorescent
      components, and it also had inherent links to so-called marine humic-like peak M
      or terrestrial humic-like peak C. Component C2 which include peak M decreased
      with increase of salinity in Jiulong Estuary, demonstrating that peak M can not
      be thought as the specific indicator of the "marine" humic-like component. Two
      humic-like components C1 and C2 showed additional behavior in the turbidity
      maximum region (salinity < 6) and then conservative mixing behavior for the rest
      estuarine region, while humic-like components C4 showed conservative mixing
      behavior for the whole estuarine region. However, the protein-like component C3
      showed nonconservative mixing behavior, suggesting it had autochthonous estuarine
      origin. EEMs-PARAFAC can provide fluorescent fingerprint to differentiate the DOM
      features for three tributaries of Jiulong River. The observed linear
      relationships between humic-like components and absorption coefficient a (280)
      with chemical oxygen demand (COD) and biological oxygen demand (BOD5) suggest
      that the optical properties of CDOM may provide a fast in-situ way to monitor the
      variation of the degree of organic pollution in estuarine environments.

PMID- 20698252
TI  - [Scattering and backscattering characteristics of Lake Chaohu].
AB  - Lake scattering characteristics are of great significance for remotely-sensed
      retrieval model development. In this study, scattering and backscattering
      coefficients of Lake Chaohu were observed through AC-S and ECO-BB9 meters, and
      their spectral properties were correspondingly analyzed. Then Power function is
      utilized to model particulate scattering and backscattering spectra, and spectral
      slope parameters obtained by simulation are 0.86 and 3.24, separately. The
      proposed scattering and backscattering models present relatively low predicative
      errors. Particulate scattering coefficients are closely related to TSM and ISM,
      with corresponding correlative coefficients of 0.91 and 0.94. Their relationships
      can be simulated well through linear function, and further specific scattering
      coefficients of TSM and ISM were proposed to be 0.636 4 (10(-3) m2 x mg(-1)) and
      0.910 8 (10(-3) m2 x mg(-1)). In addition, particulate backscattering ratio in
      Lake Chaohu has a variation range of 0.003-0.026, and refractive index varies
      from 1.02 to 1.06, which displays no large variation spans when compared with
      that in previous studies.

PMID- 20698253
TI  - [Interpretation of spatial distribution pattern for dissolved inorganic nitrogen
      concentration in coastal estuary using hyperspectral data].
AB  - Choosing dissolved inorganic nitrogen (DIN) as one of the representative
      nutritional salt monitoring indexes, a hyperspectral remotely sensed inversion
      model was built and applied to quantitatively retrieve water quality parameters
      with its spatial distribution patterns in coastal estuary with high suspended
      sediment concentration (SSC). It was found that when SSC was larger than 0.1
      kg/m3, DIN concentration had a notable inverse correlation with SSC and the
      correlation coefficient R2 reached 0.617. Based on this conclusion, firstly the
      in-situ observed water surface remote sensing reflectance was resampled according
      to the spectral response characters of Hyperion sensor. And then, statistical
      correlation analysis between reflectance and DIN concentration was carried out.
      The results showed that band reflectance of R804 and R630 representing the second
      and first reflectance peak of water spectrum curve were sensitive to the
      variation of DIN concentration. And then, a pseudo remotely sensed sand parameter
      index R804 x R630/(R804 - R630) was calculated for the construction of the
      nonlinear DIN quantitative reversion model. Correlation coefficient R2 between
      observed and simulated DIN concentrations for 29 calibrating samples and 10
      validating samples were 0.746 and 0.67, while their mean absolute errors reached
      109.07 and 147.58 microg/L, respectively. The model was then applied on Hyperion
      hyperspectral image to get the spatial distribution character of DIN
      concentration in Sheyanghe river estuary and the DIN concentration was between 52
      to 513 microg/L. Results indicated that in coastal estuary which was dominated by
      suspended sediments, the diffusive trends of DIN concentration reversed by remote
      sensing techniques had an intimate relationship with motions of tidal current and
      transportation attributes of SSC. As the hydrodynamic conditions were unclear,
      hyperspectral remote sensing technique was an effective technical way for dynamic
      survey of DIN concentration.

PMID- 20698254
TI  - [Distribution of organic carbon and carbon fixed strength of phytoplankton in
      Enteromorpha prolifera outbreak area of the Western South Yellow Sea, 2008].
AB  - Based on the analysis of dissolved organic carbon (DOC), particulate organic
      carbon (POC) and particulate nitrogen (PN) of the samples collected from stations
      in Enteromorpha prolifera outbreak area of the Western South Yellow Sea during
      the period August 9-13 of 2008, combining with the data of environmental
      hydrology, the horizontal distribution, source and influential factors of organic
      carbon and carbon fixed strength of phytoplankton were discussed. The results
      showed that the concentrations of DOC and POC ranged from 1.55 mg/L to 3.22 mg/L,
      0.11 mg/L to 0.68 mg/L, with average values of 2.44 mg/L and 0.27 mg/L. The
      horizontal distributions of DOC and POC were similar in study area. The
      concentrations of DOC and POC in coastal area were higher than that in the outer
      sea and the concentrations of DOC and POC at surface water layer were higher than
      those at the bottom water layer. There were a positive correlation between POC
      and TSS, indicating that the concentrations and source of TSS were main factors
      for the POC. According to the univariate linear regression model between POC and
      PN, the concentrations of particulate inorganic nitrogen (PIN) were evaluated.
      Removing the content of PIN in the samples, the average POC/PON values in most
      coastal waters were less than 8, combining with the values of POC/chlorophyll a,
      suggesting that the marine primary production were the important source of POC in
      most coastal waters, and the presence of degraded organic matter which derived
      from degraded Enteromorph prolifera was in the latter period of green tide
      outbreak. The results of evaluated carbon fixed strength based on primary
      productivity showed that carbon fixed strength of phytoplankton in Enteromorpha
      prolifera outbreak area of the Western South Yellow Sea ranged from 167 mg/(m2 x
      d) to 2017 mg/(m2 x d), with the average of 730 mg/(m2 x d). The daily carbon
      fixed quantities of the study area were up to 2.95 x 10(4) t. Then the daily
      carbon fixed quantities of the Yellow Sea were 28.03 x 10(4) t.

PMID- 20698255
TI  - [Impact of typhoon "Fung-wong" on the distribution patterns of heavy metals in
      the Quanzhou Bay].
AB  - Based on the inductively coupled plasma mass spectroscopy (ICP-MS) data of
      concentrations of 7 heavy metals (including Cr, Ni, Cu, Zn, Cd, Pb and As) in
      suspended particles and surface sediments samples collected at 6 and 1 13-hours
      mooring stations, respectively, in Quanzhou Bay 4 days after the landing of
      typhoon "Fung-wong". The average contents of Cr, Ni, Cu, Zn, As, and Cd are 60.4,
      50.3, 26.5, 101.7, 3.36, 40.0 and 0.180 microg/g, respectively, in the surface
      sediments, and are 1.108-7.408, 0.476-3. 394, 0.809-5.046, 3.190-19.337, 0.087
      0.595, 2.621-10.073 microg/L and 4.160-50.828 ng/L, respectively, in different
      stations in the suspended particles. The contents and distribution patterns of 7
      heavy metals during a tidal cycle were significantly changed after typhoon "Fung
      wong" by contrasting with that in same stations and tidal time at an ordinary
      situation. The contents of heavy metals, besides Ni, evidently decreased but the
      distribution patterns were similar with that in an ordinary condition with
      relatively large grads after typhoon "Fung-wong" in the surface sediments at
      station Q4. While in the suspended particles, the contents of heavy metals were
      evidently increased with the distribution patterns varied obviously and
      differently due to their geographical position after typhoon "Fung-wong". These
      impacts of typhoon "Fung-wong" to the contents and distribution patterns of heavy
      metals could be attribute to the "second contamination" and the increased supply
      of particles materials from continent during the typhoon process. The results of
      this study provide a reference to accurate assessing and scientific governing the
      heavy metals' contamination, and provide a directly support to evaluating the
      integrated impacts of typhoon process on the contamination of heavy metals in the
      Quanzhou Bay.

PMID- 20698256
TI  - [Effect of various factors on ozone inactivating Giardia in water].
AB  - In order to study the effect of O3 inactivating Giardia in water, different
      factors (CT value, pH, temperature, turbidity, organic content and inorganic
      ions) which might influence the inactivation were investigated by using
      fluorescence staining method. The results indicated that the whole process of O3
      inactivating Giardia could be divided into two periods, the inactivated rate in
      log phase was significantly faster than it in the slow phase [k1 = (5.64 +/-
      0.023) x 10(-1) mg x min, k2 = (2.72 +/- 0.002) x 10(-2) mg x min, k1 >> k2].
      When the turbidity was 0.1 to 20. 0NTU, temperature was 5 to 35 degrees C, pH was
      6.0 to 9.0, HA content was 0.5 to 10.0 mg/L, the turbidity was lower, the higher
      inactivating ratio could be received. With the increasing of temperature, the
      inactivating effect was decreased. The ability of O3 inactivating Giardia was
      stronger under acidic condition than it was in alkali circumstance. When the
      reaction system contained higher concentration of organics, the competition
      reaction might take place between Giardia and organics with O3, which might
      reduce inactivation ratio. The sequence of affecting disinfectant ability of O3
      was NO3- > None > SO4(2-) > HCO3-, while inorganic cations (Ca2+, Mg2+ and Cu2+)
      promoted the inactive reaction to a certain extent. If the CT value of O3 was
      more than 15.0 min x mg/L, the ratio of inactivation could exceed 99.0% during
      disinfecting drinking water.

PMID- 20698257
TI  - [Study on the variation of algal activity during the electrochemical oxidation as
      inactivation method].
AB  - The paper studied the variation of algal activity during the electrochemical
      inactivation and the influence factors by the use of TTC-dehydrogenase activity
      and neutral red staining assays. The treatment reactor was consisted of Ti/RuO2
      rod as anode and stainless steel pipe as cathode. The results showed that algal
      inactivation rate was 45% in cell density after 30 min treatment at 8 mA/cm2.
      Whereas the decrease of TTC-dehydrogenase activity was 94% and neutral red
      staining percentage was 100%. The algae after treatment was unable to regrow and
      it revealed that the algal activity assays can reflect the inactivation effect
      more correctly than cell density. The electrolytes could influence the
      inactivation efficiency. The electrolytes of Na2SO4 and NaNO3 had similar effects
      on algal inactivation and Na2SO4 concentration had small influence on the
      treatment. However, when the electrolyte contained 0.1 mmol/L NaCl, the algal
      inactivation was improved obviously with the 87% for TTC-dehydrogenase activity
      decrease and 82% for neutral red staining ratio. The initial algal concentration
      also influenced the treatment efficiency. If cell density increased, the
      inactivation efficiency decreased significantly. All algal cells in samples with
      cell density of 4.4 x 10(7) cells/L were completely inactivated by the use of
      natural water as electrolyte within 1 minute.

PMID- 20698258
TI  - [Impacts of suspended solids on "tailing" phenomenon in disinfection of sewage
      with chlorine].
AB  - The impacts of suspended solids in secondary effluent on "tailing" phenomenon in
      disinfection of E. coli with chlorine were investigated using kinetic
      disinfection curves. Higher SS concentration led to earlier beginning of
      "tailing" region with lower inactivation level. Comparison between lg-lg
      regression analyses of disinfection curves demonstrated that the SS concentration
      correlated with overall inactivation rate, which decreased by 10 times while SS
      concentration increased from 6 to 85 mg/L. The results of segmental modeling of
      disinfection curves showed that the SS concentration (at a range of 10-55 mg/L)
      correlated with the starting time of "tailing" region as well as the log-kill at
      the starting point of tailing region (R2 > 0.99). The starting time was shortened
      from 330 min to 55 min, and the log-kill dropped from 5.8 down to 0.8 with SS
      concentration increasing. Better removal of SS will improve the lg-kill of E.
      coli at tailing region and the inactivation rate, resulting in lower cost of
      construction and running. In addition, higher chlorine dosage and lower pH value
      could slightly enhance the log-kill in the "tailing" region.

PMID- 20698259
TI  - [Activated sludge model based COD fractionation in wastewater characterization].
AB  - The successful application of activated sludge model (ASM) in wastewater
      treatment plant mainly depends on the correctness of wastewater fractionation.
      Based on three batch oxygen uptake rate (OUR) tests, a COD fractionation protocol
      and the corresponding Matlab program were developed to aid the standardization of
      COD fractionation in wastewater. COD fractionation results of two wastewater
      treatment plants (WWTP) in Shanghai show that COD in wastewater of the Quyang
      WWTP is composed of 8.1% +/- 1.6% readily biodegradable COD (S(s)), 6.3% +/- 2.2%
      soluble inert COD (S(I)), 45.5% +/- 3.5% slowly biodegradable COD (X(S)), 31.1%
      +/- 2.1% particulate inert COD (X(I)) and 9.0% +/- 1.1% heterotrophic biomass
      (X(H)), and those fractions in wastewater of the Bailonggang WWTP are 11.1% +/-
      2.2%, 9.9% +/- 2.0%, 38.9% +/- 10.7%, 23.3% +/- 9.8% and 16.9% +/- 1.8%,
      respectively. Compared to the Quyang WWTP, wastewater of the Bailonggang WWTP
      showed lower X(S) and X(I) contents in COD, but greatly higher X(H)/COD value,
      indicating that long pipeline transportation could significantly influence the
      concentration of COD fractions.

PMID- 20698260
TI  - [Modelling nitrogen and phosphorus transfer in Potamogeton malaianus Miq.
      decompostion].
AB  - Potamogeton malaianus Miq. is one of the dominant species of submerged aquatic
      vegetations in Lake Taihu, China. The decomposition of its debris and metabolic
      detritus is an important part of nutrients cycling in the lake water. Nitrogen
      and phosphorus transfer model in P. malaianus Miq. decomposition has been set up
      based on an indoor P. malaianus Miq. decomposition experiment to quantitatively
      characterize the decomposition process. It mainly focuses on the dissolving
      process of inorganic nitrogen and phosphorus in P. malaianus Miq., the
      degradation process of its organic nitrogen and phosphorus, and the boundary's
      adsorbing process of nitrogen and phosphorus in water. There are eight state
      variables in the model, including inorganic and organic nitrogen in P. malaianus
      Miq., inorganic and organic phosphorus in P. malaianus Miq., total nitrogen and
      total phosphorus in water, and nitrogen and phosphorus adsorbed on container
      boundary. The model calibration showed a good accordance with the observed
      results of P. malaianus Miq. decomposition experiment. The dissolve rates of
      inorganic nitrogen and phosphorus in P. malaianus Miq. are 0.04 d(-1) and 0.06 d(
      1) respectively. And the decompose rates of these two state variables are 0.005
      25 d(-1) and 0.010 44 d(-1) respectively. Model outputs show that 6.7% nitrogen
      and 35.8% phosphorus can release from P. malaianus Miq. in the former 5 days.
      Phosphorus release is prior to nitrogen due to the bigger inorganic/organic ratio
      of phosphorus than that of nitrogen in P. malaianus Miq., Decomposition of P.
      malaianus Miq. could be affected by water temperature, and the affection is
      slight when water temperature is lower according to the model. The model also
      showed that P. malaianus Miq. decomposition process has influences on water
      quality in the former days, which can be eliminated by adsorbing process later.

PMID- 20698261
TI  - [Study on the removal of nitrogen and phosphorus from wastewater by Chlamydomonas
      reinhardtii].
AB  - Chlamydomonas reinhardtii was employed to remove nitrogen and phosphorus from
      wastewater. The effects of initial NH4(+) -N and TP concentrations, N/P ratios,
      Light/Darkness ratios, pH and immobilization on the removal of NH4(+) -N and TP
      were evaluated. The results showed that C. reinhardtii could almost 100% remove
      NH4(+) -N and TP as initial concentrations of NH4(+) -N and TP were no more than
      55 mg x L(-1) and 7 mg x L(-1), respectively, whereas the removal ratio of NH4(+)
      -N decreased drastically to 50% with initial NH4(+) -N concentration coming up to
      75 mg x L(-1). Under N/P ratios of 5:1 and 10:1, C. reinhardtii could completely
      remove NH4(+) -N within 3d, while 6 d was needed with N/P ratio being 25: 1.
      Different from NH4(+) -N removal, the removal ratio of TP could reach almost 100%
      within 4 d under 3 N/P ratios. With L/D ratios of 24 h: 0 h and 12 h: 12 h, 100%
      removal of NH4(+) -N and TP could be achieved by C. reinhardtii, but the removal
      rate under L/D ratio of 24 h: 0 h was relatively faster. The optimal pH range for
      C. reinhardtii to remove NH4(+) -N and TP was 6-7. After immobilization, the
      ability of C. reinhardtii to remove NH4(+) -N was significantly enhanced as the
      removal ratio of NH4(+) -N came up to 100% with initial NH4(+) -N concentration
      being 75 mg x L(-1). The ability of immobilized C. reinhardtii to remove TP kept
      stable, whereas the removal rate was slowed slightly.

PMID- 20698262
TI  - [Removing nitrate-nitrogen from wastewater using rotten wood as carbon source].
AB  - In this research, COD release of rotten wood was studied and rotten wood was
      investigated as the sole carbon source as well as biofilm carrier to remove
      nitrate from wastewater in up-flow laboratory reactor. The experimental results
      indicated that rotten wood could release carbon source continuously. COD released
      of rotten wood inoculated with humus was 2. 3 times higher than that of
      sterilized rotten wood, and VFA was 5 times. The research of denitrification was
      carried out at 25 degrees +/- 1 degrees C, 30 mg/L of initial NO3(-) -N
      concentration and 12 h of hydraulic retention time. Nitrate removal efficiency
      was above 80%. A time-dependent decrease in nitrate removal efficiency was
      observed after 46 days of operation. The results showed that rotten wood could be
      used as an effective carbon source for denitrification.

PMID- 20698263
TI  - [Dechlorination degradation of 2,4-D by nanoscale Fe3O4].
AB  - Reductive transformation of 2,4-Dichlorophenoxyacetic acid (2,4-D) by nanoscale
      Fe3O4 was studied, and the effects of 2,4-D initial concentration, the dosage of
      nanoscale Fe3O4, pH and temperature on degradation rate of 2,4-D were
      investigated. The results showed that 48% 2,4-D with initial concentration of 10
      mg/L was transformed within 48 h in the presence of 300 mg/L nanoscale Fe3O4. The
      degradation of 2,4-D was a reductive dechlorination process, and the
      concentration of chloride ion increased sharply with the degration of the 2,4-D.
      Disappearance of parent species and formation of reaction intermediates and
      products were analyzed by LC/MS. The transformation of 2,4-D followed a primary
      pathway of its complete reduction to phenol and a secondary pathway of sequential
      reductive hydrogenolysis to 2,4-dichlorophenol (2,4-DCP), 4-chlorophenol (4-CP)
      or 2-chlorophenol (2-CP) and phenol. The degradation equations of 2,4-D by
      nanoscale Fe3O4 conformed to pseudo-first-order kinetics, and the reaction rate
      constant (K) of 4-CP, 2,4-DCP and phenol were 0.0043 h(-1), 0.0026 h(-1) and
      0.0032 h(-1), respectively. The degradation rate increased with an increase in
      initial concentration of 2,4-D from 0 mg/L to 10 mg/L, and increasing the dosage
      of nanoscale Fe3O4 from 0 mg/L to 300 mg/L. The pH of reaction solution
      significantly influenced reductive degradation of 2,4-D, and the optimum pH value
      was 3.0. Besides, high temperature could improve dechlorination rate of 2,4-D.

PMID- 20698264
TI  - [Degradation mechanism of phenol with electrogenerated hydrogen peroxide on a
      Pd/C gas-diffusion electrode].
AB  - Using a self-made Pd/C gas-diffusion electrode as the cathode and Ti/IrO2/RuO2 as
      the anode, the degradation of phenol was investigated in an undivided
      electrolysis device by the electrochemical oxidation process. Hydroxyl radical
      (*OH) was determined in the reaction mixture by the electron spin resonance
      spectrum (ESR). The result indicated that the Pd/C catalyst in Pd/C gas-diffusion
      electrode system accelerated the two-electron reduction of O2 to H2O2 when
      feeding air, which is in favor of producing *OH. After 120 min electrolysis in
      Pd/C gas-diffusion electrode system, the steady concentration of H2O2 was 7.5
      mg/L. The removal efficiency of phenol and COD reached about 97.2% and 50% after
      120 min electrolysis, respectively, which suggested that most of phenol were
      oxidized to intermediates using the Pd/C gas-diffusion electrode. Furthermore,
      the ratio of BOD5/COD of the solutions was 9.1 times larger than the initial
      ones. Hence the electrochemical oxidation can enhance the biodegradation
      character of the phenol solution. The degradation of phenol was supposed to be
      cooperative oxidation by direct and/or indirect electrochemical oxidation at the
      anode and H2O2, *OH produced by oxygen reduction at the cathode. UV-Vis and GC-MS
      identified catechol, hydroquinone, and benzoquinone as the main aromatic
      intermediates, and adipic, maleic, fumaric, succinic, malonic, and oxalic acids
      as the main aliphatic carboxylic intermediates. A reaction scheme involving all
      these intermediates was proposed.

PMID- 20698265
TI  - [Removal of bisphenol A and tetrabromobisphenol A membrane by nanofiltration from
      water source].
AB  - The removal efficiency of BPA and TBBPA by nanofiltration membrane Desal 5 DK has
      been investigated with a lab-scale dead-end filtration module and the role of
      adsorption of two molecules on membrane was also explored to understand the
      filtration mechanism. The results showed that the R(obs) of BPA decreased from
      89% to 47% as the accumulated adsorption quantity of BPA onto the membrane
      increased to 30 microg x m(-2). The high BPA concentration in adsorption layer
      caused the water flux decline especially at high pressure. The high TBBPA
      rejection of over 95% by Desal 5 DK was obtained due to the molecular weight and
      molecular structure although the accumulated adsorption quantity of TBBPA reached
      50 microg x m(-2). The desorption test showed that the TBBPA could not pass
      through the membrane for its structure at the 5 x 10(5) Pa, while BPA could
      diffuse through the membrane and the peak concentration was obtained after 30 mL
      filtration. The quantity of BPA released from the membrane contributed 30% of the
      total amount adsorbed by the membrane Desal 5 DK.

PMID- 20698266
TI  - [Comparison of the effect of solution environment on humic acid removal behavior
      with charged and traditional neutral ultrafiltration membranes].
AB  - Experiments were performed to evaluate the effect of solution environment (pH
      value, ionic strength and Ca2+) on humic acid removal and membrane fouling during
      filtration of humic acid through charge-modified regenerated (RC) ultrafiltration
      (UF) membrane and traditional unmodified neutral RC UF membrane. Results showed
      that: (1) the pH value changed the net charge on humic acid molecule and charged
      membrane through protonation effect, which further influenced the ultrafiltration
      behavior. When the solution pH value decreased from 7.5 to 3.5, the rejection
      coefficient of HA decreased from 92% to 79%, and the flux decline increased from
      26% to 36% at 4 h filtration time on charged UF membrane; (23) the ionic strength
      influenced the ultrafiltration behavior through the change of humic acid molecule
      property and electrostatic shielding effect. In each solution with ionic strength
      of 0 mmol/L, 3 mmol/L and 100 mmol/L, the rejection coefficient decreased with
      the value of 92%, 87% and 48% respectively, and the flux decline increased with
      the value of 26%, 35% and 63% respectively at 4 h filtration time on charged
      membranes; (3) the effect of Ca2+ concentration on ultrafiltration behavior was
      due to the complementary effects of electrostatic shielding, Ca2+ bridge and the
      compact property of the cake layer. (4) the effect of pH value, ionic strength
      and Ca2+ concentration on the neutral membrane was similar to that on the charged
      membrane, but in different degrees. Results provide important guidance on the
      choice of appropriate solution environment when using charged ultrafiltration
      technology.

PMID- 20698267
TI  - [Effect of charged ultrafiltration membrane on natural organic matter removal and
      membrane fouling].
AB  - With the deterioration of water pollution and stringency of water standards,
      ultrafiltration (UF) has become one of the best alternatives replacing
      conventional drinking water treatment technologies. However, UF is not very
      effectively to remove natural organic matter (NOM) due to the comparatively large
      pore size compared to the size of NOM. Fouling issue is another factor that
      restricts its widespread application. The rejection coefficient and flux decline
      during ultrafiltration of humic acid (HA) and raw water through neutral
      unmodified and negatively charge-modified regenerated cellulose (RC) membranes
      were investigated, and the analysis for membrane resistance was provided. The
      initial removal rate for HA is 59% and the flux decline is 32% on neutral
      unmodified RC membrane with MWCO of 100 x 10(3), while the initial removal rate
      for HA increases to 92% and the flux decline decreases to 25% on negatively
      charge-modified RC membrane. Compared to neutral unmodified RC membrane, the
      removal rate for NOM on negatively charge-modified RC membrane increases 20% and
      the flux decline decreases 12%. Results indicated that charged UF membrane could
      be an effective way for better removal of NOM and reduction of the membrane
      fouling due to the electrostatic interaction with the combination effect of
      membrane pore size.

PMID- 20698268
TI  - [Removal of lead from aqueous solutions by complexation-ultrafiltration with
      chitosan].
AB  - Polyethersulphone (PES) membrane was chosen and chitosan was used as complexing
      agent to remove lead ions by complexation-ultrafiltration. Effects of solution
      pH, Pb2+/chitosan ratio, ionic strength and Ca2+ on the rejection coefficient of
      lead were investigated. The effect of concentration time on lead rejection
      coefficient and membrane flux was also studied. The value of pH was found to be
      the key parameter in the process of complexation-ultrafiltration. The rejection
      coefficient of lead goes high to over 99% at pH 6.0 with the Pb2+/chitosan ratio
      0.25. The increase of ionic strength and Ca2+ is not beneficial to the lead
      removal by complexation-ultrafiltration. The chitosan-metal complex was acidified
      and then the chitosan was regenerated by diafiltration. The regenerated chitosan
      was used to remove Pb2+ by complexation-ultrafiltration, and the rejection
      coefficient of lead was found to be 96.2%, which shows no significant difference
      with that obtained on the fresh chitosan. Results showed that complexation
      ultrafiltration can effectively remove lead from aqueous solutions and chitosan
      can be effectively regenerated.

PMID- 20698269
TI  - [Removal of chrysoidine from water by functionalized mesoporous material SBA-16].
AB  - A series of functionalized SBA-16 were synthesized and subsequently oxidized into
      sulfonic functionalized mesoporous silica mixing tetraethyl orthosilicate (TEOS)
      and 3-mercaptopropyltriethoxysilane (TMMPS), with triblock copolymers pluronic
      (F127) and cetyltrimethyl ammonium bromide (CTMABr) served as the mixing template
      by combination of hydrothermal and co-condensation method. The materials were
      characterized by X-ray diffraction, nitrogen gas sorption and SEM. The results
      show that the resulting functional materials belong to mesoporous materials when
      n(TEOS): n(TMMPS) is 3-8. The removal of Chrysoidine from water reaches the
      highest by functionalized mesoporous material when n(TEOS): n(TMMPS) is 7.
      Compared with different pH values, when the pH value ranges from 4-5 the
      adsorption reaches the highest.

PMID- 20698270
TI  - [Relationship among coagulation effect of Al-based coagulant, content and
      speciation of residual aluminum].
AB  - The application of AlCl3, Al2 (SO4)3 and poly-aluminum chloride (PAC) in humic
      acid-kaolin simulated water was studied in this article. It is intended to
      discuss the relationship among coagulation effect of Al-based coagulants in humic
      acid-kaolin simulated water and content and speciation of residual aluminum. It
      was found that, the turbidity removal efficiency and UV254 removal efficiency
      could reach about 90% at the tested dosage. At higher dosage, PAC gave better
      coagulation effect. The residual total aluminum content and residual aluminum
      ratio of PAC, which was 0.9 mg/L and - 3.0% or so respectively, were greatly
      lower than those of AlCl3 and Al2 (SO4)3. The residual total dissolved aluminum
      was the predominant content in the effluent after coagulation and sedimentation
      by the three Al-based coagulants. For the total dissolved aluminum, the
      proportion of dissolved organic aluminum was significantly higher than that of
      other aluminum speciation. With respect to humic acid-kaolin simulated water, the
      content of residual total aluminum in the effluent after coagulation and
      sedimentation by PAC decreased obviously compared to AlCl3 and Al2 (SO4)3. PAC
      could effectively decrease the content of residual dissolved aluminum speciation
      which has higher toxicity. The content of residual total dissolved aluminum in
      the effluent after coagulation and sedimentation by PAC was about 0.6 mg/L.

PMID- 20698271
TI  - [Research on adsorption mechanism of NOM on metal oxide particles/water
      interface].
AB  - The adsorption of humic acid molecules on metal oxide (hematite) particles/water
      interface was studied, with humic acid used as a representative of natural
      organic matter. This paper mainly analyzed influences of pH values and ionic
      strength on the adsorption coordinate reaction, as well as on the adsorption
      density and the size of aggregating-particles. The adsorption density decreased
      with pH values increasing and increased as ionic strength increased, while the
      size of aggregating-particles increased firstly and then decreased with pH value
      increasing, and increased with the ionic strength increasing. When pH value was
      4, the adsorption density was the largest, i.e. 6.22 mg/m2, while the size of
      aggregating-particles was the smallest. When pH value was 5, the adsorption
      density was smaller, but the size of aggregating-particles was larger. When pH
      value was 8, it reached the isoelectric point of coordination reactions,
      therefore the adsorption density and the size of aggregating-particles were all
      considerably small. When pH value was 10, the adsorption density is the smallest,
      i.e. 0.50 mg/m2, and the size of aggregating-particles is also smaller. Finally,
      the SS/SF hybrid model was introduced briefly, and used to analyze the adsorption
      configurations of humic acid molecules on hematite particle/water interface
      preliminarily. When pH value was low, the configurations were mostly train and
      loop, when pH value was high, the configurations were mostly tail. The higher the
      ionic strength was, the more train and tail configurations there were. The lower
      the ionic strength was, the more loop configurations there were.

PMID- 20698272
TI  - [Adsorption of fluoride ions on a Ca-deficient hydroxyapatite].
AB  - A Ca-deficient hydroxyapatite (d-HAp) from the by-product of phosphate wastewater
      treatment has been used to remove fluoride ions. The effects of pH, coexistent
      calcium and magnesium ions, and chloride ions on the adsorption efficiency were
      investigated for the system. The results showed that d-HAp adsorbed F-
      efficiently within a wide pH range (4-7), and the defluoridation capacity of d
      HAp remained 85%. There was no significant effect on removal of fluoride ions
      with addition of up to 200 times as high a concentration of Ca2+, Mg2+ and Cl-,
      so it suggested that d-HAp was applicable to high fluoride area. The adsorption
      kinetics can be described by Pseudo-second-order reaction model and the
      correlation coefficient R2 was 0.999 0. It was also found that the adsorption of
      F- on d-HAp followed the Langmuir model. The maximal static adsorption capacity
      was calculated as 26.11 mg x g(-1). It also suggested that ion exchange was the
      main mechanism during this adsorptive process.

PMID- 20698273
TI  - [Effects of acid and heating treatments on the structure of sepiolite and its
      adsorption of lead and cadmium].
AB  - The effects of acid and heating treatment on the structure of sepiolite and its
      adsorption capacities for Pb2+ and Cd2+ were investigated using X-ray powder
      diffraction, infrared spectroscopy, surface area analyses and batch sorption
      experiments in this paper. The results showed that the BET surface area of the
      sepiolite samples grew with increase concentrations of HCl and prolong treatment
      time and no obvious structural changes were observed. CaCO3 as the impurity in
      the natural sepiolite can not be removed completely in the treatment process with
      0.5 mol x L(-1) HCl. The surface area of sepiolite treated with 6 mol x L(-1) HCl
      and continuous stirring 72 h reached the maximum 301.47 m2 x g(-1). A decrease in
      the BET surface area was observed for the samples treated with acid at higher
      temperature. The BET surface area of samples treated with different acid species
      arranged in the order HCl > HNO3 > H2SO4. The calcinations process decreased the
      BET surface area from 21.44 m2 x g(-1) at 100 degrees C to 0.17 m2 x g(-1) at 900
      degrees C. The adsorption results indicated that despite increases in the surface
      areas upon acid activation, improvements in the adsorption were not observed for
      heavy metal Pb2+ and Cd2+ ions. Pb2+ ions have higher affinity for specific
      adsorption onto the sepiolite samples than Cd2+ ions. H2SO4 treatment was found
      to be more effective for the removal of Pb2+ and Cd2+ ions than HCl and HNO3
      treatments. It is apparent that PbSO4 and CdSO4 were formed during the sorption
      process. The calcinations treatment exhibited no significant effects on the
      adsorption of Pb2+ ions onto sepiolite, but the adsorption of Cd2+ ions obviously
      increased above 700 degrees C.

PMID- 20698274
TI  - [Adsorption of methylene blue onto vanadium-doped magnetite].
AB  - A series of vanadium-doped magnetite (Fe3-x VxO4, x < 0.4) synthesized by an
      oxidation-precipitation method, were characterized using chemical analysis, X-ray
      diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), as well as
      thermogravimetric and differential scanning calorimetry (TG-DSC) analyses. The
      obtained results show that the synthetic Fe3-x VxO4 has spinel structure while
      vanadium mostly replaces Fe3+ in the octahedral sites. The synthetic Fe3-x VxO4
      is magnetic material, with crystal size ranging from 28 to 35 nm. The
      substitution of vanadium in the magnetite structure increases the amount of
      surface hydroxyls. The experimental adsorption results indicate that, in neutral
      pH condition, the maximum adsorption capacities of Fe3-x VxO4 increase obviously
      with the increase of vanadium concentration in magnetite while the adsorption
      isotherm complies well with the Langmuir model. The adsorption of methylene blue
      (MB) on Fe3-x VxO4 can get equilibrium in the first 25 min, supporting a pseudo
      second order equation. Moreover, the rise of the solution pH value results in an
      increase of the adsorption capability of MB on Fe3-x VxO4.

PMID- 20698276
TI  - [Formation and environmental implications of iron-enriched precipitates derived
      from natural neutralization of acid mine drainage].
AB  - Acid mine drainage (AMD) and its natural neutralizing products in Wangjiatan iron
      mine were collected and analyzed by using spectroscopic and electron
      microanalytic methods. The results show that after natural neutralization of AMD
      by surface water of the stream, acidity and electric conductivity of AMD are both
      decreased. While for dissolved elements, no other element is obviously decreased
      except for Fe3+, SO4(2-), and Ca2+. For precipitates formed by natural
      neutralization, Fe is enriched and ferrihydrite is the main iron mineral, with
      little amount of goethite and fibroferrite contained in downstream precipitates.
      To ferrihydrite, 2-line and 6-line ferrihydrite are the main mineral type in
      upstream and downstream precipitates, respectively. Furthermore, for all
      precipitates, two layers are observed. In outer layer 2-line ferrihydrite is the
      main mineral, while in inner layer 6-line ferrihydrite and goethite are the main
      minerals. Ferrihydrite dominated precipitates are favorable in immobilizing toxic
      and hazardous elements. Furthermore, it is demonstrated that pH and the
      concentration of SO4(2-) are decisive factors for ferrihydrite formation. The
      ferrihydrite translocation and its attenuation for toxic elements are, to a great
      extent, affected by hydrodynamics in neutralization zone.

PMID- 20698275
TI  - [Extraction of main constituents from rice straw and their sorption of pyrene].
AB  - Main constituents (lignin, cellulose and hemicelullose) were extracted from rice
      straw, and characterized by elemental analysis and Diffuse Reflectance Infrared
      Fourier Transform Spectroscopy (DRIFT). Sorption of pyrene on rice straw and its
      main constituents was studied. The results showed that there are great
      differences in the properties of the three constituents, with lignin of higher
      aromaticity and lower polarity, while cellulose and hemicellulose of greater
      polarity and aliphaticity. Sorption of pyrene also differed a lot due to the
      varied characteristics of the sorbents. All isotherms were fitted well with
      Freundlich equation. Lignin showed the greatest sorption capacity for pyrene,
      with K(F) being 5.04 x 10(4), approximately 100 times greater than that of
      cellulose. Sorption of pyrene on hemicellulose was even a little smaller than
      that on cellulose. At low solute aqueous concentration (c(e) = 0.01 S(w)), the
      sorption of pyrene on rice straw was controlled by lignin, and sorption
      coefficient (K(d)) was a little smaller than that predicted by the K(d) value on
      lignin and its mass fraction. This suggested that some sorption sites such as
      alkyl and aromatic centers were covered when the lignin existed mixed in the rice
      straw. But at high concentration (c(e) = 0.5 S(w)), the K(d) value of pyrene on
      rice straw was markedly greater than the sum of those on three constituents,
      suggesting that partition on other constituents could not be neglected. Moreover,
      pyrene sorption isotherm on lignin was nonlinear (Freundlich exponent, n = 0.89),
      while sorption on the other three sorbents was more linear (n > 0.96). A negative
      relationship between n and aromaticity was observed, which illustrates that
      specific effect related with aromaticity is the main reason for nonlinearity.
      Organic carbon normalized sorption coefficients (K(oc)) increased with increasing
      aromaticity and decreased with increasing polarity of the sorbents.

PMID- 20698277
TI  - [Sediment record of DDTs in sediment core from Hongfeng reservoir].
AB  - In order to reconstruct the chronology of 2,2-his (4-Chlorophenyl)-1,1,1
      trichloroethane (DDT) input into the Hongfeng reservoir and assess the pollution
      issues, the temporal distribution of DDT in sediment core from Hongfeng reservoir
      was measured using GC/MS method, and the possible sources and potential risk
      assessment also had been identified. The DDTs (sum of p,p'- and o,p'-DDT, DDE and
      DDD) in sediment core were ranged from 7.6 to 23.7 ng/g, and roughly, ever
      decreased from the bottom to the surface sediment. In detail, a sharp decline of
      DDTs concentration in sediment was found from 1981 to 1983, followed by a tardy
      decrease trend to the present. The DDTs in sediment were mainly composed of p,p'
      DDTs (sum of p,p'-DDT, DDE and DDD). The ratio of p,p'-DDTs to o,p'-DDTs (sum of
      o,p'-DDT, DDE and DDD) ranged from 5.1 to 8.4, which suggests that the DDTs in
      sediment were chiefly originated from the technical DDT. Meanwhile, the DDTs in
      sediments were dominated by the metabolites of DDT (DDD and DDE) and the ratio of
      DDT/(DDD + DDE) were between 0.31 and 0.84, indicating the DDTs in sediment were
      mostly stemmed from the historical usage. Besides, the vertical profile of the
      ratios of DDT/( DDD + DDE) and DDE/DDD indicate that possible usage of technical
      DDT still occurred in the drainage area of Hongfeng reservoir around 1990,
      although the usage of technical DDT in agriculture has been banned in 1983. The
      residue levels of DDE, DDD, DDT, and DDTs in surface sediment from Hongfeng
      reservoir were all between ERL and ERM, suggesting potential risk could occur,
      and the contamination of DDT in Hongfeng reservoir deserving more concerns.

PMID- 20698278
TI  - [Spatial distribution characteristics of organic carbon in the soil-plant systems
      in the Yellow River estuary tidal flat wetland].
AB  - Well-understand the organic carbon status in the Yellow River delta is the most
      important for studying the biogeochemical processes of the muddy-sandy coastal
      wetland and ecological restoration. The spatial distribution characteristics and
      its impact factors of organic carbon in the plant-soil systems of new-born tidal
      flat wetland in the Yellow River estuary were studied. The results showed that
      the difference of plant organic carbon content in different plant communities
      were not obvious, however significant difference of the plant organic carbon
      density was observed. Moreover, the M-shaped spatial distribution of the plant
      organic carbon density, which was similar to the plant biomass, was found in the
      study. The organic carbon contents in top soils were varied from 0.75 to 8.35 g x
      kg(-1), which was much lower than that in the typical freshwater marsh wetlands
      ecosystem. The spatial distribution trend of soil organic carbon density was
      similar to the soil organic carbon. The correlation analysis showed that soil
      organic carbon density was negatively correlated with pH, and positively
      correlated with TN, C/N and salinity. However, the correlations of plant organic
      carbon density with the soil organic carbon density, TN, C/N, pH and salinity
      were not significant.

PMID- 20698279
TI  - [Survey and assessment of heavy metals in soils and herbal medicines from Chinese
      herbal medicine cultivated regions].
AB  - Concentrations of As, Hg, Pb, Cd in soils and herbal medicine samples from
      cultivated regions of Anguo City in Hebei Province were analyzed and assessed,
      and the bioconcentration factors of different herbal medicines were studied and
      discussed as well. The results showed that the average contents of As, Hg, Pb, Cd
      in soils from herbal medicine cultivated regions were 12.9, 0.036, 15.6, 0.118 mg
      x kg(-1), respectively. Concentrations of heavy metals in soils were lower than
      class II of the soil environmental quality standard. When local soil background
      values of heavy metals were used as assessment standard, among the 16 cultivated
      regions the percentage of As, Hg, Ph, Cd belonging to lightly pollution class
      were 18.75%, 43.75%, 0%, 100%, respectively based on the single pollution index.
      And the Nemerow index results were between 1 and 2, which suggested the soils
      were at slight pollution level. However, when quality standard class II was used,
      both the single pollution index and Nemerow index did not exceed 0.7, which means
      that soils investigated were generally safe for cultivation of Chinese herbal
      medicines. The assessment of heavy metals in herbal medicines showed that the
      pollution indices of most herbal samples (< 95%) were lower then 1. Cd
      bioconcentration factors of Aster tataricus L. and Anemarrhena asphodeloides
      Bunge, Hg bioconcentration factors of Angelica dahurica (Fisch. ex Hoffm.) Benth.
      et Hook. f. and Glehnia littoralis F. Schmidt ex Miq. were above 1. Therefore,
      the accumulation characteristic of heavy metals in Chinese herbal medicines
      should be fully concerned when GAP base soil quality assessment was taken.

PMID- 20698280
TI  - [Evaluation of soil heavy metals accumulation in the fast economy development
      region].
AB  - Evaluation of soil heavy metals accumulation was studied in Kunshan City, a
      typical region of the fast economy development region in China. 126 soil samples
      were collected and analyzed, and evaluation indexes of soil heavy metal
      accumulation, which including total concentration of soil heavy metal index
      (THMI), soil available heavy metal index (AHMI) and fractionation of soil heavy
      metal index (FHMI), were established, and the heavy metal accumulation conditions
      of soil in this region were also discussed. Results showed as follows: the
      spatial variability of THMI was relative lower, with a mean value of 42.57%,
      whereas strong variability was found in AHMI and FHMI (especially active fraction
      of soil heavy metals), with the average value of 82.75% and 77.83%, respectively.
      Judging by each index reference standard of C Horizon, THMI was low-grade with a
      mean value of 1.01, while the AHMI and FHMI reached to medium accumulation and
      serious accumulation, with the average values of 2.46 and 4.32, respectively. The
      synthetic accumulation index of soil heavy metals (SHMI) was 2.56, reaching to
      medium grade level and with strong variability. 21.54% land area was in low-grade
      accumulation and 54.70% land area was in medium grade accumulation, while 23.76%
      land area was in serious accumulation under SHMI evaluation system. All the
      accumulation evaluation indexes in livestock breeding zone were the lowest, while
      the indexes in the smelting and plating zone were the highest, but the indexes
      difference between two zones were unobvious. There were markedly differences in
      soil types, which the accumulation indexes in Wushan soil were significantly
      higher than those in Huangni soil and Qingni soil.

PMID- 20698281
TI  - [Application of local Moran's I and GIS to identify hotspots of Ni, Cr of
      vegetable soils in high-incidence area of liver cancer from the Pearl River
      Delta, South China].
AB  - The index of local Moran's I is a useful tool for identifying hotspots of soil Ni
      and Cr, and for classifying them into spatial clusters and spatial outliers. To
      identify hotspots of vegetable soils Ni and Cr in high-incidence area of liver
      cancer, Shunde area of Foshan City, Pearl River Delta Economic Zone, 208 topsoil
      samples were collected from vegetable fields to measure the contents of nickel
      (Ni) and chromium (Cr). The results showed that the mean concentrations of two
      heavy metals Ni, Cr were 33.21 mg/kg, 80.84 mg/kg, respectively, Which were 130%,
      60% higher than their soil background values of Guangdong Province, respectively.
      Generally, Ni is partly accumulated in soil but the accumulation of Cr is not
      obvious at all. The local Moran's I of Ni and Cr was calculated using 3 000, 6
      000, 9 000 m as distance bands, respectively. The hotspots of Ni and Cr elements
      in soils were identified by local Moran's I which computed based on 6 000 m;
      "individual hotspots" are in the north which were affected by anthropogenic
      factors; "regional hotspots" are in the south which were controlled by parent
      materials. Moreover, the distributions of "regional hotspots" of Ni, Cr are the
      same as that of the highest mortality rate of liver cancer, this consistence
      could come up with a research direction that could reveal environmental etiologic
      factors of liver cancer.

PMID- 20698282
TI  - [Effects of rice straw on the diversity of nitrifying genes (amoA and hao) in
      paddy soil].
AB  - The effects of long-term (16 years) fertilization on the diversity and community
      structure of soil ammonia-oxidizing gene (amoA) and hydroxylamine-oxidizing gene
      (hao) in paddy soil were evaluated using the methods of polymerase chain
      reaction, cloning and sequencing. The soil samples were collected from the
      treatments of NPK (CK) and NPK plus rice straw (SR) of the long-term field
      fertilization experiment in Taoyuan Agro-ecological Experimental Station. The
      Shannon Indices showed that the diversity of amoA and hao in SR treatment was
      lower than that in CK, and LUBSHUFF statistical analyses demonstrated that the
      sequence compositions of both amoA and huo libraries were significantly different
      between CK and SR. The phylogenetic trees indicated that some clusters appeared
      in SR treatment but were not detected in CK treatment. As to amoA, only
      Nitrosospira besides the uncultured amoA sequences were cloned from the two
      treatments, while no Nitrosomonas species were detected. As to hao, the strains
      from Silicibacter and Methylococcus were dominant in CK, while in SR the strains
      from Nitrosospira and Nitrosomonas were dominant. Sum up, the long-term rice
      straw application has caused a remarkable impact on the diversity and community
      structure on Nitrosobacteria.

PMID- 20698283
TI  - [Effect of carbon source and dissolved oxygen on denitrification by aerobic
      denitrifier Pseudomonas mendocina AD6].
AB  - Aerobic denitrifying performances of P. mendocina AD6 at various C/N ratios,
      dissolved oxygen (DO) concentrations and carbon sources including citrate,
      acetate, and glucose were evaluated through flask experiment. At an insufficient
      carbon concentration, namely C/N ratio of 3, total nitrogen (TN) removal
      efficiency was 42% by aerobic denitrification. When the C/N ratio was increased
      to 8, 15, and 23, the TN removal efficiency by AD6 quickly increased to 55%, 70%,
      and 69%, in which 7%, 20%, and 25% of TN losses could be contributed to the
      aerobic denitrification by AD6, respectively. Batch cultures were carried out in
      a series of 250 mL conical flasks containing 100, 50, and 25 mL of the nitrate
      supplemented basal medium with C/N ratio of 15, DO of 7.15-8.08 mg/L and strain
      AD6. Flasks were shaken in a rotary shaker at 28 degrees C and 180 r/min to allow
      better gas exchange. DO concentration of culture medium declined rapidly to
      anoxia condition at the beginning of reaction followed by an aerobic level with
      above 2 mg/L of DO after 24 h reaction. Different carbon sources had strong
      influence on the aerobic denitrifying performance of strain AD6. The maximum
      consumption rates of citrate, acetate, and glucose by strain AD6 were 90%, 92%,
      and 41%, respectively. In the medium spiked with acetate as carbon source, TN
      removal efficiency and N losses due to aerobic denitrification increased to 14%
      and 5%, respectively, with comparison to that spiked with citrate. Evaluation on
      nitrogen removal performances of aerobic denitrifier should be cautious with
      flask experiment because aerobic, partial aerobic and total anoxic growing
      conditions could be changed by C/N ration and carbon source of medium.

PMID- 20698284
TI  - [Domestication study about desulfuration microorganism from oxidation ditch by
      low concentration SO2].
AB  - An excellent desulfuration microorganism with a quick growth and propagation,
      high activation, high efficiency of removing SO2 is obtained from oxidation ditch
      of a city sewage treatment plant by inductive acclimatization over 6 d with low
      concentration SO2 gas (100-2 000 mg/m3). The desulfurition microorganism get
      their energy sources for growth from transforming SO2 (SO3(2-)) to SO4(2-). The
      predominant bacterium of the desulfuration microorganism has the same
      characteristic with Thiobacillus ferrooxidans (T. ferrooxidans), which showed
      that it was Gram negative, short rod bacteria with a single polar flagellum under
      a microscopic examination, and obtained its nourishment through the oxidation of
      inorganic compounds. The technology process condition of domestication and
      desulfuration of microorganism are particular studied, and the results showed
      that aerating time, SO2 flux and time to provide nutriment contained N, P, K to
      microorganism were very important. They have an ability with degradation rate of
      160g/ (m3 x h) and degradation efficiency over 50% to transform sulfite to
      sulfate in liquid phase. The bacteria have a 98% of removing efficiency and over
      80% of biodegradation efficiency for the 5 500 mg/m3 SO2 gas and the outlet
      concentration of SO2 is lower than 100 mg/m3, and also have a 95% of removing
      efficiency for 15 000 mg/m3 SO2 gas in the packed tower reactor with Raschig ring
      at 3s contact time.

PMID- 20698285
TI  - [Research on sorption and transport characteristics of ligninolytic enzymes in
      different compost substances].
AB  - To understand the characteristics of ligninolytic enzymes sorption and transport
      in different compost substances, ligninolytic enzymes adsorption on soil,
      vegetable leaf, rice straw and chaff was comparatively studied through batch jar
      tests and relevant kinetics and isotherm equilibrium were discussed as well as a
      column experiment was performed to study the process of transport. The results
      showed that the sorption efficiency was depended on the sorts of substances. The
      adsorptive capacities of soil, vegetable leaf, rice straw and chaff to lignin
      peroxidase (LiP) were 1.22 U x g(-1), 1.27 U x g(-1), 1.13 U x g(-1), 1.22 U x g(
      1) and to manganese peroxidase (MnP) were 5.09 U x g(-1), 4.88 U x g(-1), 4.43 U
      x g(-1), 3.95 U x g(-1), respectively. Comparing the kinetic models of LiP and
      MnP adsorption, the pseudo-second-order reaction model (R2 0.973-0.999 7) was the
      best of the models. Elovich equation was a bit better than pseudo-first-order
      kinetic which was the worst. The equilibrium data could be fitted well with
      Langmuir model while it could not satisfied with Freundlich model. The adsorptive
      saturation of soil, vegetable leaf, rice straw and chaff to LiP were 1.23 U x g(
      1), 1.30 U x g(-1), 1.17 U x g(-1), 1.14 U x g(-1) and to MnP were 5.70 U x g(
      1), 5.19 U x g(-1), 4.73 U x g(-1), 4.14 U x g(-1). LiP and MnP had good
      transport capability in straw and chaff to move to the deepest layer of 10 mL
      while remained in the superficial layers in soil and vegetable leaf.

PMID- 20698286
TI  - [Toxic effects of dichloromethane and dichloroethane to Chlorella pyrenoidosa].
AB  - The acute toxic and biochemical effects of dichloromethane and 1,2-dichloroethane
      to Chlorella pyrenoidosa were assessed. The experimental results showed that
      dichloromethane and 1, 2-dichloroethane had some inhibition to growth of the
      algae. With increasing concentration of the organic toxicant, the cell density
      decreased. The 96 h-EC50 of dichloromethane to Chlorella pyrenoidosa was 550.1
      mg/L; the 96 h-EC50 of 1,2-dichloroethane to Chlorella pyrenoidosa was 276.0
      mg/L, toxicity of 1,2-dichloroethane is a little stronger than that of
      dichloromethane; the joint toxicity of two organic toxicants was showed as
      antagonism. Content of chlorophyll a, activities of superoxide dismutase (SOD),
      catalase (CAT) and content of malondialdehyde (MDA) in algae had been
      significantly affected under the organic toxicant exposure. The activities of SOD
      and CAT were increased at first and then decreased remarkably with the increasing
      concentration of the organic toxicant, showed as "Bell Shaped Curve". The content
      of malondialdehyde (MDA) flared up and lipid peroxidant aggregated with the
      increasing concentration of the organic toxicant. The results suggested that the
      primary mechanism of two organic toxicants on Chlorella pyrenoidosa cells may be
      related to oxidation damage of lipid and other biological large molecules caused
      by dichloromethane and 1,2-dichloroethane.

PMID- 20698287
TI  - [Growth inhibition of the four species of red tide microalgae by extracts from
      Enteromorpha prolifera extracted with the five solvents].
AB  - To study the effects of extracts of Enteromorpha prolifera on the growth of the
      four species of red tide microalgae (Amphidinium hoefleri, Karenia mikimitoi,
      Alexandrium tamarense and Skeletonema costatum), the extracts were extracted with
      five solvents (methanol, acetone, ethyl acetate, chloroform and petroleum ether),
      respectively. Based on the observation of algal morphology and the measurement of
      algal density, cell size and the contents of physiological indicators
      (chlorophyll, protein and polysaccharide), the results showed methanol extracts
      of E. prolifera had the strongest action. The inhibitory effects of A. hoefleri,
      K. mikimitoi, A. tamarense and S. costatum by the methanol extracts were 54.0%,
      48.1%, 44.0% and 37.5% in day 10, respectively. The extracts of E. prolifera
      extracted with methanol, acetone and ethyl acetate caused cavities, pieces and
      pigment reduction in cells, and those with chloroform and petroleum ether caused
      goffers on cells. The extracts of E. prolifera extracted with all the five
      solvents decreased athletic ability of the cells, among which those extracted
      with ethyl acetate, chloroform and petroleum ether decreased cell size of test
      microalgae. The further investigation found that the methanol extracts
      significantly decreased contents of chlorophyll, protein and polysaccharide in
      the cells of those microalgae. The inhibitory effect of chlorophyll, protein and
      polysaccharide contents of four species of microalgae by the methanol extracts
      was about 51%. On the basis of the above experiments, dry powder of E. prolifera
      were extracts with methanol, and extracts were obtained. The methanol extracts
      were partitioned to petroleum ether phase, ethyl acetate phase, n-butanol phase
      and distilled water phase by liquid-liquid fractionation, and those with
      petroleum ether and ethyl acetate significantly inhibited the growth of all test
      microalgae, and the inhibitory effect of four species of microalgae by those two
      extracts was above 25% in day 10. Our researches expressed that antialgal
      substances in E. prolifera extracted with methanol were obtained. And two
      fractions (petroleum ether phase and ethyl acetate phase) that inhibited the
      growth of all test microalgae were obtained when the methanol extracts was
      fractionated by liquid-liquid fractionation.

PMID- 20698288
TI  - [Rapid elimination of surface organophosphorous pollutants using hydroxyl
      radical].
AB  - According to the frequency of contamination accident for organic compounds in
      recent years, two kinds of organophosphorus pesticides dichlorvos and omethoate,
      as the simulated organic pollutants, were rapidly eliminated using spraying
      hydroxyl radical produced by strong electric-field ionization discharge method on
      an aluminium flat plate about 160 cm2. The high concentration aqueous *OH
      solution was produced from H2O(gas) and O2 with plasma reaction. In a condition,
      where pH is 6 and the initial densities of dichlorvos and omethoate on the
      simulation plane are both 60 microg x cm(-2), when the spray density of *OH
      reaches 3.9 microg x cm-2, removal efficiencies of dichlorvos and omethoate are
      90%, and mineralization rates are 64% and 72%, respectively. The effect of pH for
      removal efficiency was also investigated. The results found that the removal
      efficiency of organophosphorus pollutants first decreased slowly and then
      increased fast with the increase of pH from 2 to 12 and the lowest removal rate
      appeared when pH close to neutral. The degradation rates of dichlorvos and
      omethoate both ascend by 21% and 26% respectively with pH 12 than that of pH 6.
      Four factors and three levels orthogonal test indicated that the degradation by
      *OH played a major role at the surface oxidation removal rapid of
      organophosphorus pollutants in a short period of time.

PMID- 20698289
TI  - [Spatiotemporal trends and the impact factors of acid rain in Anhui Province].
AB  - The observational data of acid rain at seven stations in Anhui province operated
      by China Meteorological Administration (CMA), as well as the coal consumptions in
      Anhui and some surrounding provinces along with satellite measured tropospheric
      NO2 columns, were used to analyze the spatiotemporal trends of acid rain in Anhui
      and the potential reasons of the increasing occurrence frequency of acid rain. In
      addition, the technique of back-trajectory-cluster analysis was used to examine
      the impacts of transport patterns on the precipitation acidity in Anhui. The
      occurrence frequency shows the lowest in summer and the highest in autumn, with 3
      year average pH < 5.6 during 2006-2008 at all stations, hereinto, pH values are
      between 5.0 and 4.5 in Hefei, Anqing, Maanshan and Bengbu. In spatial, acid rain
      were the most severe in southern to middle Anhui and mitigated to north. The
      distributions of pH were concentrative at Fuyang, Tongling and Huangshan, with
      more than 75% occurred between 6.00-7.50 (Fuyang), 5.00-6.00 (Tongling) and 5.00
      6.50 (Huangshan); quite dispersive at other stations, with the maximum at 4.00
      4.50 (Hefei and Anqing), 5.00-5.50 (Maanshan) and 5.50-6.00 (Bengbu). The
      occurrence frequencies of acid rain increased evidently at all stations comparing
      with those in the end of 1990s. The results of back-trajectories-cluster analysis
      show that the acid rain is closely related with the regional-range transport of
      acid rain precursors at each station. The air-masses from southeast and
      northeast, especially those passing through Jiangsu and Zhejiang, associated with
      the highest frequencies of acid rain with pH < 5.0, indicating that the
      industrial emissions in the economy developed areas of Yangtze Delta play key
      roles in acid rain in Anhui province. In addition, statistics shows that the
      occurrence frequency of acid rain in Hefei was highly correlated with the trends
      of the provincial coal consumptions in Anhui, Jiangsu and Zhejiang, also
      tropospheric NO2 column content over Anhui province and surrounding areas with
      all correlation coefficients > 0.7, suggesting the close relationship between the
      quick increasing acid rain in Hefei and the regional pollutant emissions.

PMID- 20698290
TI  - [Removal of NO and Hg0 in flue gas using alkaline absorption enhanced by non
      thermal plasma].
AB  - Non-thermal plasma (NTP) induced by positive corona discharge was utilized to
      oxidize NO and Hg0 to more water-soluble NO2 and Hg2+ under the conditions of
      simulated flue gas. The effects of discharge voltage and inlet SO2 and NO
      concentrations on NO and Hg0 oxidation and their removals by alkaline absorption
      were investigated. The results show that the oxidation and removal of NO and Hg0
      are enhanced with the increase of discharge voltage. The concentrations of NO and
      NO2 at the outlet of absorption tower are 0 and 69 mg/m3 with an inlet NO
      concentration of 134 mg/m3 and a discharge voltage of 12. 8 kV while the outlet
      concentrations of Hg0 and Hg2+ are 22 microg/m3 and 11 microg/m3 with an inlet
      Hg0 concentration of 110 microg/m3 and a discharge voltage of 13.1 kV. The
      presence of SO2 slightly improves the oxidation and removal of Hg0 while it has
      almost no effect on NO oxidation and its removal. The oxidation and removal of
      Hg0 are significantly inhibited with the increase of inlet NO concentration. In
      the coexistence of 800 mg/m3 SO2, 134 mg/m3 NO and 110 microg/m3 Hg0, the removal
      efficiencies are 57% for NO and 31% for Hg0 with an energy input of 77 J/L.

PMID- 20698292
TI  - Taming the beast.

PMID- 20698291
TI  - [Comparison of bioremediation of polycyclic aromatic hydrocarbons (PAHs)
      contaminated soil by composting in the spring and winter].
AB  - In this study, lab-scale bioremediation experiments of soil contaminated by
      polycyclic aromatic hydrocarbon (PAHs) with aerated composting were compared in
      the Spring and Winter. Results showed that PAHs degradation rate in the winter
      was higher than that in the spring, and the total PAHs degradation rates were
      over 70% for both Pile 1 (the dry weight ratio of soil, swine manure and sawdust
      as 1: 1: 1) and Pile 2 (the dry weight ratio of soil, swine manure and sawdust as
      1: 3: 1), but the PAHs degradation rate of Pile 1 as 74.61% was higher than that
      of Pile 2 the degradation rates of low, middle, high benzene-ring types PAHs were
      66.46%, 79.12%, 75.88%, respectively. After composting most of kinds of PAHs
      contents in soil were less than 1 000 microg/kg (dry weight) except BbF, for
      example, BbF contents of these two piles in the Spring, 25 000 microg/kg and 20
      000 microg/kg, respectively, were much higher than those in the winter
      experiments, both less than 5 000 microg/kg. The first reaction order model was
      used to simulate degradation of PAHs during composting, and results showed that
      the model was fitted better in winter (R2 > 0.6) than in spring, and the half
      life of PAHs degradation in winter was about 13 d.

PMID- 20698293
TI  - A user-friendly home.

PMID- 20698294
TI  - The relevance for nondiscrimination compliance.

PMID- 20698295
TI  - Customized pain treatment.

PMID- 20698296
TI  - Effective rehabilitation of the hand.

PMID- 20698297
TI  - The power struggle.

PMID- 20698298
TI  - Meaningful use rules proposed electronic health record incentives under HITECH
      act.

PMID- 20698299
TI  - [Immunobiologically active compounds from skin].
AB  - This paper describes physiochemical and biological properties of 3
      immunologically active compounds extracted by acetone from porcine skin. High
      pressure gel chromatography confirmed their heterogeneity. RP-HPLC of compound 2
      (C2 or K-activin) also characterizes it as a heterogeneous entity. It was shown
      to inhibit proliferation of cultured fibroblasts from human fetuses and exhibit
      weak activity in general anaphylactic reaction (anaphylactic shock) and skin
      anaphylactic reaction. A summary of data on immunologically active compounds are
      presented with special emphasis laid on acetone-extractable K-activin.

PMID- 20698300
TI  - [Interhemisphere asymmetry of regulation of the local brain blood flow in
      patients with dyscirculatory encephalopathy].
AB  - Patients with dyscirculatory encephalopathy (DE) were examined to elucidate
      interhemisphere relationships by recording brain constant potential (CP) and
      perfusion CT. Electrophysiological characteristics were shown to relate to local
      brain blood flow. Dispersion of intrehemisphere CP level in DE patients proved
      more pronounced than in healthy subjects. Interhemisphere CP difference in
      temporal region significantly (p < 0.001) correlated with the time needed to
      reach maximum concentration of contrast agent in the frontal and temporal cortex,
      basal ganglia, and thalamus. Left temporal CP level positively correlated with
      contrast agent concentration in the above brain structures of both hemispheres
      and negatively with that in the right hemisphere. It is concluded that
      intertemporal relationships may influence vegetative nervous system that in turn
      changes cardiovascular function.

PMID- 20698301
TI  - [The possibility to predict results of aortic valve prosthetics from initial
      anatomic and functional properties].
AB  - The study included 394 patients selected for aortic valve prosthetics. Group 1
      comprised patients with prevailing aortic stenosis (n = 165 or 41.9%), group 2
      patients with prevailing aortic insufficiency (n = 229 or 58.1%). Their
      preoperative characteristics were arbitrary categorized as follows: circulatory
      disturbances (F1), anthropometric parameters (F2), central hemodynamic parameters
      (F3), anatomofuntional parameters (F4), left ventricular myocardium parameters
      (F5), valvular morphology (F6), valvular parameters (F7). Correlation analysis
      was used to predict surgery outcome. Excel 2000-based software was created to
      assess the probability of favourable outcome.

PMID- 20698302
TI  - [The role of associative symbiosis in infectious pathology].
AB  - Symbiosis as a biological basis of infectious process is considered with
      reference to the change of paradigm in symbiology and the new notion of
      associative symbiosis. The main structural and functional elements of associative
      symbiosis are reviewed and their analogy with vectors of the infectious process
      established. Special attention is given to associative symbionts (pathogenic and
      opportunistic microorganisms), their universal interaction with the host and
      predominant normal flora. Interaction between symbionts is shown to be underlain
      by variation of persisting potential of both the infectious agent and commensal
      microorganisms. Data on the role of intercellular interactions between symbionts
      at the level of pro-prokaryotes and pro-eukaryotes during infection are presented
      that unveil pathogenetic basis of the infectious process.

PMID- 20698303
TI  - [Thyroid morphology in a children population living in the environmentally
      polluted area].
AB  - Comprehensive study of the "normal" thyroid gland in fetuses and children of
      different age groups in the Chelyabinsk region revealed a number of changes
      characteristic of the so-called dysregulation pathology. The role of ecological
      factors and outcome of resuscitation and intensive therapy in these changes is
      discussed. It is shown that the development and manifestation of tumoral and non
      tumoral diseases of thyroid gland prone to a combination of various diseases are
      delayed till the school age.

PMID- 20698304
TI  - [Carcinogenic risk in residents of the Techa riverside villages].
AB  - The paper summarizes carcinogenic risk estimates in residents of the Techa
      riverside villages who have been exposed for many years to radiation due to
      discharge of radioactive wastes from the Mayak Production Association into the
      Techa-Iset-Tobol-Ob river system. Analysis of cancer incidence and mortality data
      has shown a statistically significant dose-dependent increase in the risk of both
      malignant tumors and leukemia. The dependence of excess relative risk on exposure
      dose is well described by a linear model. No evidence has been obtained that
      carcinogenic risk resulting from low-rate radiation exposure is lower than that
      from acute exposure of A-bomb survivors. Difficulties of following up vital
      status due to population migration, incomplete data on mortality causes, and
      inaccurate dose estimates are believed to be key contributors to radiation risk
      uncertainties.

PMID- 20698305
TI  - [Gestagens and the brain].
AB  - Modern data on molecular mechanisms underlying intracerebral pleutropic action
      ofgestagens (progesterone, its metabolites, and synthetic gestagens) are
      reviewed. Properties of classical and membrane-bound progesterone receptors
      involved in regulation of gene expression, modulation of neurotransmitter
      systems, and activation of signal cascades in neurons are described along with
      data of regional distribution of progesterone receptor subtypes in brain,
      metabolism, functional activity, and mechanisms of action of progesterone
      metabolites. Special attention is given to analysis of progesterone and
      metabolite neuroprotective activity in CNS, such as anti-inflammatory and
      antiapoptotic effects, and participation in neurogenesis regulation. Clinical
      application of progesterone-based drugs is discussed with reference to the
      treatment of brain injuries and prospects for extension of indications for their
      use in neurologic practice.

PMID- 20698306
TI  - [Mast cells and heparin--key links in adaptive and pathological processes].
AB  - Participation of mast cells and heparin in adaptive and pathological processes is
      discussed with special reference to heparin pool in mast cell granules.
      Hypotheses explaining conversion of normal mast cells to phenotypically
      pathologic ones are analysed. Prospects for enhancement of adaptive abilities of
      the organism and approaches to the treatment of diseased organs are discussed in
      terms of protection and restoration of heparin cells in the mast cells.

PMID- 20698307
TI  - [The place of dendritic cells in the microenviroment in Hodgkin's lymphoma].
AB  - Dendritic cells (DCs) are the least studied microenvironment elements in
      Hodgkin's lymphoma (HL). Ninety-five lymph nodes were morphologically and
      immunohistochemically studied in patients with classical HL. The authors found
      CDla- and langerin-positive DCs in the presence of T lymphocytes, which were
      localized in the close proximity to neoplastic Reed-Sternberg cells (RSCs). There
      were also CD23-positive follicular DCs, which were typically located at the
      periphery of tumor foci, in the areas of residual follicular structures, were
      surrounded by B lymphocytes and were rarely associated with RSCs. There were two
      morphologically distinct groups among the CD 1a- and langerin-positive DCs; one
      had developed cytoplasmic processes, which formed a network around the RSCs
      (probably a more mature/functionally active form); the other had round cells with
      short cytoplasmic processes, loosely distributed around the neoplastic cells (a
      less mature/active form). The function and role of CD1a- and langerin-positive
      DCs in HL call for further investigation. The topographic closeness of these DCs
      to RSCs suggests that these cells play a considerable role in the pathogenesis of
      HL.

PMID- 20698308
TI  - [The morphology of triple negative breast cancer].
AB  - Triple negative breast cancer (TNBC) does not express estrogen and progesterone
      receptors and amplified Her2/neu gene. Examining 90 cases of TNBC by traditional,
      histological, and immunohistochemical studies (70 patients) has indicated the
      heterogeneity of this group of breast neoplasms. It is represented by a great
      variety of the histological types of mainly high-grade breast cancer. The markers
      of basaloid differentiation (cytokeratins 14, 5/6, 17, and p63) in the tumor
      cells were revealed in various ratios in 49 patients. The above markers were
      absent in 21 cases. Poor prognosis in TNBC seems to be largely associated with
      the presence of the basal-like phenotype rather than that of the triple negative
      phenotype. Much work to determine specific quantitative parameters is to be done
      to define the nosological specificity of mainly the basal-like subtype of TNBC.

PMID- 20698309
TI  - [Actins and keratins in the diagnosis of human basal-like breast cancer].
AB  - The most common forms of luminal breast cancer (BC) were compared with basal-like
      and Her2/neu3+ BC. Their primary classification was based on morphological
      diagnosis and the expression of estrogen receptor (ER), progesterone receptor
      (PR), and Her2/neu receptors. Monoclonal antibodies to actins and keratins were
      used for the study. Basal-like BC cells (ER/PR/Her2/ neu-) were regularly stained
      with antibodies to basal keratins 5/6 and 17, smooth muscle alpha-actin, and p63.
      Luminal keratin 8 staining was reduced. The solid regions had beta-actin staining
      with disappearance in the scirrhous component. beta-actin and basal keratins were
      also observed in metaplastic BC with ER/PR/Her2/neu3+. Immunomorphology using
      cytoskeletal markers along with the expression of steroid hormone and Her2/neu
      receptors may be used in the diagnosis of basal-like forms of BC.

PMID- 20698310
TI  - [The comparative characterization of different forms of myocardial infarction at
      a 30-year interval].
AB  - The paper presents the results of morphological and morphometrical studies of 247
      subjects who have died from diferent forms of myocardial infarction (MI) in
      comparison with those of the study conducted by G. G. Avtandilov and K. D.
      Salbiyev 30 years ago. The performed study demonstrates that general trends in
      the occurrence and development of MI have undergone no substantial changes in the
      past 30years. The reduction in the count of platelets from 50 to 30% may be due
      to the advent of more effective anriaggregants and the use of current
      thrombolytics during both emergency care delivery and acute MI treatment. It is
      rather difficult to macroscopically define the borders of infarction at 72 hours
      after its onset for the pathological processes progress and the extent of
      infarction is expanded.

PMID- 20698311
TI  - [The implication of Chlamydia pneumoniae in damage to human aortic
      endotheliocytes in atherosclerosis].
AB  - A cytological technique was used to study the impressions of the aortic intima of
      dead patients. Endothelial cell Chlamydia pneumoniae (CP) was detected in 26
      (56.5%) of 46 dead patients; the bacterium was found in the unaffected intact
      intimal areas in 9 (19.6%) cases. Three morphological forms of CP--inclusions,
      spots, and aggregates were described. The whole life cycle of CP and the specific
      features of disintegration of the host cell--the endothelium were observed. CP
      leads to extensive infection and aponecrotic death of all types of endothelial
      cells above the fatty streaks and plaques. Focal chlamydial destruction of an
      endothelial layer results in intimal surface erosion and thrombogenesis. An
      inflammatory response to damaged endothelial cells may be responsible for the
      initiation and progression of atherosclerosis and plaque destabilization.

PMID- 20698312
TI  - [The topical problems of morphological diagnosis and the pathomorphism of HIV
      infection].
AB  - The paper analyzes the frequency of admissions to the S. P. Botkin Clinical
      Infectious Hospital and the City AIDS Center among patients with HIV infection
      and the structure of fatal outcomes. It is concluded that there is a considerable
      increase in mortality and the number of patients needing hospitalization. The
      dead HIV-infected patients autopsied at the Unit of Morbid Anatomy, S. P. Botkin
      Hospital, in the past years are characterized in detail. The topical problems of
      HIV infection the solution of which require the participation of
      pathomorphologists are discussed.

PMID- 20698313
TI  - [Myocardial architectonic changes and cardiomyocytic apoptosis in the course of
      experimental diphtheria intoxication].
AB  - Diphtheria intoxication was simulated in rabbits, by intravenously injecting
      native diphtheria toxin in a dose of 0.3 MLD (minimal lethal dose) per kg body
      weight. Intact rabbits were used as a control. Following 1, 3, and 5 days of the
      onset on intoxication, the chests were opened under 2% rometar anesthesia and the
      hearts were extirpated, semithin left and right ventricular myocardial sections
      were prepared and light microscopic morphometry (at a magnification of x 1000)
      was carried out with video-assisted imaging. The rate of cardiomyocytic (CMC)
      apoptosis was determined, by calculating the free lying nuclei - the
      morphologically changed nuclei that were present in the extracellular space. Both
      ventricular CMC destruction characteristic of necrotic death was ascertained to
      significantly increase just on day 1 of the experiment and to further enhance
      during its course. By day 5, the rate of CMC apoptosis increased in both the left
      and right ventricles. Furthermore, there was an increasing reduction in
      myocardial collagen levels.

PMID- 20698314
TI  - [Sarcomatoid carcinoma of the thymus].
AB  - Sarcomatoid carcinomas are rare malignancies composed of epithelial
      (carcinomatous) and sarcomatous elements. High-grade carcinoma is difficult to
      diagnose by light optic and immunohistochemical studies. The authors give the
      data available in the literature on sarcomatoid carcinoma of the thymus and also
      describe their own observation. Its histological pattern is represented by a
      combination of carcinomatous and sarcomatous elements with extensive necrotic
      foci. Immunohistologically, the tumor cells expressed total cytokeratin
      (AE1/AE3), CD99, and focally epithelial membrane antigen. Some tumor cells were
      vimentin- and SMA-positive. Markers, such as chromogranin A, bcl-2, bcl-6, S-100
      protein and myogenin, were negative.

PMID- 20698315
TI  - [Early recurrence of neuroborreliosis with a fatal outcome].
AB  - The authors describe a case of Lyme disease--neuroborreliosis. In
      neuroborreliosis, there are morphohistological changes: pronounced dystrophic
      processes in the brain nerve cells, spongiosis, perivascular hemorrhagic
      infiltrations, glial proliferation with the formation of perivascular glial
      granulomas.

PMID- 20698316
TI  - [From the history of the 19th century pathology. Pathology reform in the fate of
      A. I. Polunin, the first professor of pathological anatomy of Moscow University].

PMID- 20698317
TI  - [Alesandr Maksimov: from pathology works to stem cell teaching].

PMID- 20698318
TI  - [The morphological characteristics of osteoarthrosis].
AB  - Osteoarthrosis (OA) is a group of overlapping diseases that have various
      etiologies, but equal biological, morphological, and clinical outcomes. OA is
      characterized by degenerative and destructive changes in the articular hyaline
      cartilage, subchondral bone, spongiosis, synovium, capsule, and articular
      ligamentous apparatus. The clinical symptoms of OA are closely associated with
      morphological changes in articular tissue elements, primarily in the articular
      hyaline cartilage. Six stages that reflect the magnitude of changes in the
      hyaline cartilage and 4 degrees of the extent of the process along the articular
      surface are identified.

PMID- 20698319
TI  - [A solid-pseudopapillary tumors of the pancreas].
AB  - The review presents an update of solid-pseudopapillary pancreatic tumors, a rare
      and inadequately studied type of tumors that are predominantly encountered in
      girls and young women. It discusses the problems in the diagnosis based on the
      histological and imunophenotypical uniqueness of these tumors, which allows them
      to be differentiated from other types of pancreatic tumors with a less favorable
      prognosis. The correct diagnosis of a solid-pseudopapillary tumor determines the
      management tactic that requires no radiation or chemotherapy in the vast
      majority.

PMID- 20698321
TI  - [Medical supply of long flies].
AB  - The article presents a characteristics of main negative factors, disimproving a
      functional condition and working capacity of airmen in long flies: long stay in a
      working pose, necessity of using of summer form, of defense form and oxygen
      breath means, peculiarities of eating in fly, solving of nature-imposed
      necessity, relative sensor deprivation, sameliness of environment, high level of
      noise, hypokinesia, high nervous-emotional tension in conditions of air
      refueling, temperature fall, difference of barometric pressure, desynchronisms.
      Were given practical recommendations on maintenance of functional and working
      capacity of members of flying staff, realizing long flies.

PMID- 20698320
TI  - [Anemia during inflammatory processes: pathogenesis and clinical and
      morphological manifestations].
AB  - The review sums up the results of the current stage of studying the so-called
      anemia of inflammation (AI). The key mediator of AI is the polypeptide hepatic
      hormone hepcidin, the hepatocytic secretion of which is initiated by
      proinflammatory macrophageal cytokines (IL-6, IL-lalpha, and tumor necrosis
      factor-alpha) and T-lymphocyte gamma-interferon. Hepcidin has bactericidal
      properties and promotes iron retention in the enterocytes, macrophages, and
      hepatocytes through the internalization and degradation of ferroportin (a cell
      iron exporter into the plasma). The limited iron availability to microorganisms
      in AI is aimed at enhancing the body's natural resistance to infection.
      Therefore, AI serves as an example of fundamental reactions of innate immunity.
      The latent and manifest phases of AI can be identified. The major clinical and
      morphological manifestations of AI are a decreased functional iron stores and
      hepatic and splenic hemosiderosis.

PMID- 20698322
TI  - [Optimization of work of polyclinic in medical supply of attached contingents on
      the base of using of informational technologies].
AB  - The article presents review of experience of forming of information system of
      recording of visiting of policlinics and analyze of treatment measures.
      Functioning of this system on the base of local computer net permitted
      considerably improve indexes of work of policlinics.

PMID- 20698323
TI  - [Frequency and prophylaxis of the most generalized diseases among young men of
      preinduction age].
AB  - The article presents the analyze of indexes of morbidity among young men of
      preinduction age in Orenburg region. Was given a valuation of level of risk of
      forming of diseases. Were shown causes of deficit of weight, growth of pathology
      of locomotor apparatus and psychic diseases among young men of preinduction age.
      The young men before the call-up need well-timed prophylactic observes,
      dispensary observe and health measures, aimed to improve the health.

PMID- 20698324
TI  - [Using of morphological indexes of walls of arteries in effectuating of
      identification expertises].
AB  - Parameters of elasticity of an arterial wall and its water-salt structure were
      investigated. Authentic age changes of parameters of elasticity of arteries wall
      and absence of age dependence of changes of its water-salt structure are
      revealed. In result perspectivity of use of parameters of elasticity of an
      arterial wall for development of a method of definition of age and the decision
      of a question on an belonging of parts of a body has been shown one individual on
      an age parameter at medicolegal examination of dismembered corpses.

PMID- 20698325
TI  - [Role of modern neuro-physiological methods of diagnostics in increasing of
      quality of medical aid to veterans of the Great Patriotic War].
AB  - Was observed the structure of morbidity among veterans with using neurocomputer
      methods of diagnostics. Morbidity level among veterans is twice higher than in
      other age groups. Veterans of the Great Patriotic War have acute chronicle
      diseases of nervous system, coursing against systemic atherosclerosis and
      decreasing of vicarious capabilities of organism. It requires increasing of
      resources of healthcare on pre-hospital and stationary levels of organization of
      medical aid. Implementation of high-technological computer measures of
      diagnostics promote to prevent of sthenic sequels of encephalopathy, hypertonic
      crisis, insult, epilepsy and parkinsonism. Using these methods are realized early
      diagnostics on functional level, timely pathogenesis therapy and medical
      rehabilitation of veterans. Organization of medical aid to veterans requires more
      full cooperation between institutes of healthcare and institutes of social
      defense.

PMID- 20698326
TI  - [Comparative characteristics of operative treatment of growth of urocyst].
AB  - The authors effectuated a retrospective analyze of operative treatment of 108
      patients with carcinoma of urocyst in urological unit of the 2nd CMCH by Mandryka
      P. V. for the period of 1995-2007.

PMID- 20698327
TI  - [Peculiarities of systemic on regional circulatory dynamics at a
      pseudoexfoliative syndrome and pseudoexfoliative glaucoma (review of
      literature)].
AB  - The article presents results of searches, devoted to haemodynamic damages against
      wide-spread ophthalmo-pathology--pseudoexfoliative syndrome and pseudoexfoliative
      glaucoma. Changes, appearing on different levels, confirm hypothesis about
      systemic character of the disease and prove the necessity of further examination
      of role of syndrome in development of different forms of vascular disease.

PMID- 20698328
TI  - [Experience of sanitarium-epidemiological scouting during effectuating of field
      operations of units of navy infantry].
AB  - The article presents an experience of organization of sanitary-hygiene and
      controepidemic measures, preceding going to brigade of marine corps on missions.

PMID- 20698329
TI  - [Quality of a life of military seamen of Northern fleet].
AB  - Research of quality of a life of military seamen with use of the Russian-speaking
      version of the general questionnaire of health "Medical Outcomes Study-Short
      Forms" (SF-36) is conducted. 600 military men at the age from 18 till 55 years
      are surveyed. Military seamen have highly appreciated the quality of a life.
      Absolute values of indicators of quality of a life on all scales 70 points that
      is considered, how very high there are more. The physical component of health is
      estimated by military men above, than psychological. Values of indicators of
      quality of a life on all scales of questionnaire SF-36 at men were above, than at
      women, with preservation of the general tendency more an appreciation of a
      physical component of health. Military men on an appeal have estimated the
      quality of a life above, than military men under the contract. Essential
      distinctions in an estimation of quality of a life in group of military men under
      the contract it is not revealed.

PMID- 20698330
TI  - [Psychiatric aid during the Great Patriotic War].
AB  - The article presents an observe of questions of organization of psychiatric aid
      during the Great Patriotic War, main disadvantages of the first period of war,
      their dependence from circumstances of prewar period, ignoring of experience of
      last war. There was marked the role of famous native psychiatrists in
      organization of psychiatric aid to military servicemen in theatre of combat
      actions.

PMID- 20698331
TI  - [War and medicine].
AB  - The article presents the observe of contribution of medicine in victory of the
      Great Patriotic War (1941-1945). Main attention was paid to organization of carry
      over of wounded person from battle-field and delivery of health care. There was
      created a sharp system of medical securing of combat actions of troops on the
      base of principle of stage treatment of ill and wounded persons, in combination
      with their evacuation in corresponding places. The end treatment was laid on a
      large net of specialized medical institutes, evacuation hospitals of People's
      Committee of Health care of USSR. A great value had the organization of
      controepidemic work. Thanks to feat of military physicians, activity of civil
      health care and international help in organization of treatment of ill and
      wounded persons there was returned in order 17 157 243 persons.

PMID- 20698333
TI  - [From memories about war].

PMID- 20698332
TI  - ["Everything, made by soviet military medicine during the last war, could be
      called a feat..."].
AB  - The article presents an observe of different aspects of activity of military
      medical service of the Red Army for the period of the Great Patriotic War on the
      base of complex examination of archive sources and large sphere of literature.
      Was shown contribution of several representatives of military service, their work
      on front and in rearwards.

PMID- 20698334
TI  - [Dobroslavin A.P. and native military hygiene (To the 125th anniversary of
      edition of the "Course of military hygiene")].
AB  - Professor Dobroslavin A.P.--the founder of scientific military hygiene in Russia,
      pioneer of hygiene preparedness of military physicians. His "Course of military
      hygiene"--is the first Russian edition on this topic.

PMID- 20698335
TI  - What kids can teach us.

PMID- 20698336
TI  - Health reform. Discount drug program could save eligible hospitals millions of
      dollars.

PMID- 20698337
TI  - Supply chain. Flu survey shows significant cracks in supply chain.

PMID- 20698338
TI  - Other voices. Assembling practical tools to excel at reform. Interview by Bill
      Santamour.

PMID- 20698339
TI  - Electronic health records. States setting high standards for EHR use.

PMID- 20698340
TI  - Billing & coding. ICD-10: experts fear executive attention lags.

PMID- 20698341
TI  - Patient care. Paging Dr. Picasso.

PMID- 20698342
TI  - Design & construction. Can going green get you into the black?

PMID- 20698343
TI  - Accidents happen.
AB  - How prepared are you to respond to a crisis? And how ready are you to learn from
      any mistakes?

PMID- 20698344
TI  - 'Meaningful use' hoists hospital IT to next level.
AB  - The winners of H & HN's annual survey of information technology use among
      hospitals and health systems. Plus: the Most Wired-Small and Rural, Most Improved
      and Most Wireless. And we consider how leaders of top IT hospitals plan to make
      "meaningful use" a guide for improvement.

PMID- 20698345
TI  - Does your GPO deliver the goods?

PMID- 20698346
TI  - The long-distance trustee.

PMID- 20698347
TI  - MRSA: Hospitals step up fight. Will it be enough?

PMID- 20698348
TI  - 2010 Circle of Life Awards.

PMID- 20698349
TI  - Putting people first: value-driven health care.

PMID- 20698350
TI  - Lessons learned.

PMID- 20698351
TI  - Chemopreventive efficacy of topical difluoromethylornithine and/or triamcinolone
      in the treatment of actinic keratoses analyzed by karyometry.
AB  - OBJECTIVE: To determine whether low-dose topical applications of
      difluoromethylornithine (DFMO) with or without Triamcinolone (Fougena, Melville,
      New York, U.S.A.) to moderately sun-damaged skin with actinic skin keratoses are
      efficacious. STUDY DESIGN: There were 4 topically administered, 6-month
      treatments, DFMO + Eucerin (Beiersdorf Inc., Hamburg, Germany), DFMO +
      Triamcinolone, Triamcinolone + Eucerin and Eucerin + Eucerin (to serve as double
      placebo). Participant eligibility included evidence of at least 2 actinic
      keratoses on each posterolateral forearm as well as moderate to severe evidence
      of sun-damaged skin, as evaluated by a board certified dermatologist. High
      resolution digitized imagery of nuclei from histologic sections of 4-mm punch
      biopsies from sun-damaged skin on the posterolateral forearms was recorded, at
      baseline and at the end of 6 months of study. RESULTS: With 102 participants and
      185 skin biopsies, a total of 16,395 skin cell nuclei were recorded. The nuclei
      were analyzed to assess the changes in the pattern of the nuclear chromatin. Two
      specific measures of end point evaluation were computed, including the percentage
      of nuclei with high values of nuclear abnormality and the reduction of the
      percentage of nuclei assigned by a discriminant function to the baseline data
      set. All 3 active interventions, including low-dose topical DFMO, topical
      Triamcinolone and topical DFMO + Triamcinolone, led to statistically significant
      reductions of both the number of nuclei with high nuclear abnormality as well as
      the number of nuclei assigned to the baseline data set. These reductions were
      found for all 3 treatments involving DFMO or Triamcinolone. For the placebo data
      sets only small, statistically insignificant increases or decreases of these
      percentages were observed. CONCLUSION: The low-dose, topical drug interventions
      were all effective in reducing skin biopsy nuclear abnormality by a statistically
      significant 15-20%, whereas there was no evidence of a double placebo effect by
      karyometric assessment. These effects were greater than the case-to-case sampling
      error.

PMID- 20698352
TI  - Expression of redox pathway enzymes in human prostatic tissue.
AB  - OBJECTIVE: To evaluate the involvement of thioredoxin reductase (TxnR),
      thioredoxin (Trx) and peroxiredoxins (Prdx) in prostate cancer (PCa) and to
      assess the potential prognostic importance of these redox-regulated pathways.
      STUDY DESIGN: Expression of the isoforms TxnR2, Trx1 and Prdx2 was studied by
      immunohistochemistry on tissue microarrays (TMAs). In a prognostic TMA, 294
      primary cases of PCa with a median follow-up of 49 months were stained for Trx1
      and Prdx2. Another TMA containing benign prostatic tissue, atrophy, high grade
      prostatic intraepithelial neoplasia (HGPIN) and PCa from 40 patients was stained
      with all 3 antibodies. RES ULTS: All 3 proteins showed similar expression
      patterns, with the highest immunoreactivity in HGPIN followed by atrophy, PCa and
      benign tissue. TxnR2, Trx1 and Prdx2 were overexpressed in HGPIN and PCa compared
      with benign tissue (p < 0.001), and Trx1 and Prdx2 were also overexpressed in
      HGPIN compared with PCa (p < 0.001). Trx1 and Prdx2 did not correlate with
      biochemical recurrence. CONCLUSION: This study demonstrates up-regulation of the
      redox pathway proteins in PCa and its precursor lesions. The pathogenetic role of
      the redox system remains to be investigated.

PMID- 20698353
TI  - Digital morphometric characterization of mucosal surface lesion patterns under
      magnification colonoscopy.
AB  - OBJECTIVE: To study quantified mucosal surface patterns of digitized colonoscopic
      images obtained with 17-40x magnification and chromoscopy of hyperplastic,
      adenomatous lesions and adenocarcinomas confirmed by histology. STUDY DESIGN:
      Morphometric measures were performed on at least 10 image files of each lesion
      and compared to normal mucosa at the same distance and area from each image.
      Thirty-seven hyperplastic lesions, 42 adenomas and 26 carcinomas from 105
      patients were studied. Three morphometric characteristics were evaluated in
      lesions and normal mucosal surface area from each case: pit counts per area, pit
      diameter and pit area. RESULTS: Pit counts per area and pit area of lesions as
      compared to the normal mucosa of the same cases showed statistically significant
      differences in the 3 groups of lesions studied (p < 0.001). CONCLUSION: Real-time
      morphometric evaluation is feasible during videocolonoscopy with magnification
      roughly equivalent to a 5x microscopic field. Automated evaluation of
      morphometric characteristics as part of Bayesian Belief Network software may
      prove a useful information source for the colonoscopist's diagnostic decision.

PMID- 20698354
TI  - Analysis of the capture and influence of nanoparticles on the cytotoxic effects
      of 7-ketocholesterol on cardiac cells: investigation by flow cytometry and by
      dynamic and spectral imaging microscopy associated with factor analysis of
      medical image sequences.
AB  - OBJECTIVE: To evaluate the capture of nanoparticles (quantum dots [QDs],
      fluorospheres) by nonbeating mouse cardiac cells (HL1-NB) cultured without or
      with 7-ketocholesterol (7KC) found at an increased level in the plasma of
      atherosclerotic patients and to simultaneously analyze their cytotoxic,
      proinflammatory and oxidative properties. STUDY DESIGN: Flow cytometry (FCM),
      confocal laser scanning microscopy and subsequent factor analysis image
      processing were used to characterize the uptake of nanoparticles and to define
      their cytotoxicity, evaluated by enhanced permeability to SYTOX Green, release of
      lactate dehydrogenase (LDH) and morphologic nuclear changes determined with
      Hoechst 33342. Proinflammatory effects were estimated by enzyme linked
      immunoassay to quantify IL-8 and MCP-1 secretion. The overproduction of reactive
      oxygen species (ROS) was determined by FCM with hydroethidine. RESULTS: Whereas
      the nanoparticles had no cytotoxic or inflammatory effects, they could stimulate
      ROS production. QDs were not incorporated. When 7KC was used, LDH release was
      enhanced and QDs potentialized IL-8 secretion. The incorporation and exit
      dynamics of nanoparticles were visualized to differentiate the emission spectra
      of SYTOX Green and nanoparticles and to precisely determine the cellular
      localization of nanoparticles. CONCLUSION: The selected nanoparticles, which
      accumulate at the inner or outer cytoplasmic membrane level, can induce biologic
      activities and are able to interfere with those of chemically defined molecules
      such as 7KC.

PMID- 20698355
TI  - Liquid-based cytology in DNA-based molecular research: viability and potential
      application.
AB  - OBJECTIVE: To evaluate the effectiveness of UCM and PreservCyt liquid media in
      molecular analysis using exfoliated oral cells and analyze Tp53 codon 72
      extracted from these cells. STUDY DESIGN: Exfoliated oral cells were placed in
      UCM and PreservCyt preservation media. DNA was isolated by proteinase K/phenol
      chloroform protocol. Quantity and quality was measured by Nanodrop 1000. To
      evaluate the applicability of the isolated DNA to molecular techniques, DNA from
      oral cells was used to analyze Tp53 codon 72 polymorphism and GADPH genes.
      RESULTS: DNA was successfully isolated from all samples, with an average
      concentration of 56.52 +/- 34.68 ng/microL for UCM and 42.13 +/- 25.50 ng/microL
      for PreservCyt. Average 260/280 ratios were 1.83 +/- 0.06 for UCM and 1.74 +/-
      0.11 for PreserveCyt. Analysis of Tp53 codon 72 by polymerase chain reaction
      restriction fragment length polymorphism was performed for all samples, with 4%
      of Pro/Pro, 60% of Arg/Arg and 36% of Arg/Pro genotype. In the analysis of GADPH
      multiplex polymerase chain reaction, fragments varying from 100 to 400 bp were
      obtained from all samples. CONCLUSION: Cytologic liquid media are suitable for
      preserving cell samples for posterior DNA isolation and molecular analysis and
      could become reliable research tools.

PMID- 20698356
TI  - Utility of tissue microarrays for assessment of chromosomal abnormalities in
      chromophobe renal cell carcinoma.
AB  - OBJECTIVE: To compare the results of numerical chromosomal changes in chromophobe
      renal cell carcinoma obtained from whole tissue sections with those of tissue
      microarrays. STUDY DESIGN: Standard sections and tissue microarrays constructed
      from formalin-fixed and paraffin-embedded chromophobe renal cell carcinomas from
      6 patients were subjected to interphase fluorescence in situ hybridization (FISH)
      using centromeric probes for chromosome 1, 2, 6, 10 and 17. Tissue microarrays
      were constructed with 3 cores per tumor and 2 cores of normal renal tissue
      controls. RESULTS: Whole sections of chromophobe renal cell carcinoma showed
      multiple chromosomal abnormalities in 3 out of 6 cases (case 1, 2, 5). In 2 cases
      all 5 chromosomes were lost in both whole and tissue microarray cores (cases 2
      and 5), and for 1 case (case 1) losses of chromosomes 2, 10 and 17 were detected
      on both whole and tissue microarray cores. In another 2 cases there were 2
      fluorescence signals for chromosomes 1 in the majority of malignant cells (cases
      3 and 6), loss of chromosome 6 (case 3), loss of chromosome 2 (case 6) and a
      mosaic pattern with nuclei showing a mixture of signal losses and gains for the
      other chromosomes. The remaining tumor did not show abnormalities (case 4). When
      2 core biopsies per tumor were examined, the level of substantial concordance of
      results ranged from 92% to 98%. CONCLUSION: In this study we have demonstrated
      that tissue microarrays are a valid substitute for whole tissue sections in large
      cohort studies of chromophobe renal cell carcinoma when FISH analysis is
      undertaken. Concordance of results was improved when the number of analyzed cores
      was increased from 2 to 3, at which point a concordance index ranging from
      substantial to almost perfect was observed.

PMID- 20698357
TI  - Evaluation of a real-time polymerase chain reaction assay using analyte-specific
      reagents for detection of methicillin-resistant Staphylococcus aureus nasal
      carriage.
AB  - OBJECTIVE: To validate a real-time polymerase chain reaction (PCR) assay for the
      detection of methicillin-resistant Staphylococcus aureus (MRSA) that is capable
      of accommodating 30 patient samples in a single batch without compromising the
      level of sensitivity and specificity associated with PCR testing. STUDY DESIGN: A
      real-time PCR analyte-specific reagent (ASR) assay was compared to conventional
      culture methods using dual swab samples collected from the nares of 151 patients.
      RESULTS: Of the 151 specimens, 49 (32%) were positive for MRSA by PCR, whereas 40
      (26%) were positive by culture methods. The Roche LightCycler 2.0 (Roche
      Diagnostics, Indianapolis, Indiana, U.S.A.) and its associated ASRs were capable
      of analyzing 30 patient samples and 2 controls in < 2 hours. Current data suggest
      that 4-10% of our patient specimens harbor both coagulase negative Staphylococcus
      and S aureus in the same sample. Samples such as this are reflexed to culture,
      only 24% of which contain MRSA. Efficiency in the laborato-ry was greatly
      improved. The sensitivity, specificity, positive predictive value and negative
      predictive value were 100%, 92%, 82% and 100%, respectively. CONCLUSION: The
      Roche LightCycler 2.0 PCR platform is a sensitive and efficient screening method
      for determining the nasal carriage of MRSA with a rapid turnaround time in the
      clinical laboratory.

PMID- 20698358
TI  - Epidermal growth factor receptor gene promoter methylation in primary colorectal
      tumors and corresponding metastatic sites: a new perspective for an "old"
      therapeutic target.
AB  - OBJECTIVE: To clarify the role of epidermal growth factor receptor (EGFR)
      promoter methylation in primary colorectal cancers and corresponding metastases
      and its relationship to EGFR expression. STUDY DESIGN: Formalin-fixed tumor
      samples (primary site and metastasis)from colorectal cancer patients were
      analyzed for EGFR promoter methylation and EGFR immunohistochemistry expression.
      RESULTS: Among the 63 assessable patients, 25 cases (39.7%) showed EGFR promoter
      methylation. Forty-two primary colorectal tumors and corresponding metastases
      were available for paired analysis of EGFR methylation status. EGFR methylation
      status of the primary tumor was in accordance with that of metastasis in 29
      patients (69%). In contrast, 7 patients (50%) with EGFR promoter methylation in
      the primary tumor showed unmethylated EGFR in metastasis, and 6 metastases (46%)
      showed EGFR promoter hypermethylation derived from unmethylated EGFR primary
      tumors. Lack of EGFR protein expression was observed in 8 EGFR promoter
      methylated primary tumors (44%) and in 7 EGFR promoter methylated metastatic
      sites (44%). CONCLUSION: EGFR promoter hypermethylation does not seem to
      represent a rare event in colorectal cancer and may be present differently in
      different tumor sites. These findings may be relevant to further studies
      investigating the role of EGFR in colorectal cancer patients.

PMID- 20698359
TI  - Expression of alpha-methylacyl coenzyme A racemase in partial and complete focal
      atrophy on prostate needle biopsies.
AB  - OBJECTIVE: To describe the behavior of alpha-methylacyl coenzyme A racemase
      (AMACR) in focal atrophy including all subtypes. Focal prostatic atrophy is the
      benign lesion that most frequently mimicks adenocarcinoma particularly the
      partial variant. STUDY DESIGN: We analyzed the immunohistochemical expression of
      AMACR in normal glands and acini of adenocarcinoma, partial atrophy and all
      variants of complete atrophy of a total of 1,198 acini on needle prostatic
      biopsies. RESULTS: Partial atrophy showed negative and weak expression of AMACR
      in 143/190 (75.3%), and 47/190 (24.7%) acini, respectively. The secretory
      (luminal) compartment in all variants of complete atrophy showed aberrant
      immunohistochemical expression: AMACR negative, prostate-specific antigen
      negative and 34betaE12 positive, suggesting an intermediate phenotype for these
      cells. CONCLUSION: No strong positivity was seen in partial atrophy; however, the
      absence of basal cells in 23.2% acini of partial atrophy and the weak positivity
      seen in 24.7% acini that overlaps with 22.5% acini with weak expression in
      adenocarcinoma may be a pitfall for the correct interpretation in the
      differential diagnosis of cancer. Recognizing the hematoxylin-eosin features of
      partial atrophy is still the most critical aspect in preventing a misdiagnosis of
      adenocarcinoma.

PMID- 20698360
TI  - Succeeding with failure.

PMID- 20698361
TI  - Can you hear me now?
AB  - Based on the results of available literature, it appears that most NICU's are not
      adhering to the sound level recommendations as advised by the AAP. The excessive
      noise levels are placing infants at risk for both short-term and long-term
      negative health outcomes. NICU staff, hospital administrators, and visitors need
      to be educated on the deleterious effects of increased sound levels. Paying
      special attention to detail when designing and altering the NICU environment will
      also help to eliminate sources of increased noise. Eliminating excessive noise in
      the NICU environment is essential in promoting positive health outcomes for
      preterm and term infants.

PMID- 20698362
TI  - Plague of icy breath. Cholera and the gateshead community 1831-1832.
AB  - The impact of cholera epidemics on communities around the world during the 19th
      century has generated a vast array of resources for the medical historian.
      However, the more readily available testimonies of doctors and local boards of
      health dominate the literature, whilst our understanding of the experience of
      individuals, particularly the destitute victims of cholera and their families, is
      sparse.This article analyses a collection of unpublished documents assembled by
      an antiquary, John Bell, from Gateshead, North-East England, in 1831-1832, in
      order to reconstruct the experience of the local community as they prepared
      themselves for the arrival of cholera and how they responded to its devastating
      effects. The paper concludes by examining the enduring changes prompted by the
      community reaction to the cholera outbreak of 1831-1832, including the
      establishment of the Gateshead Dispensary.

PMID- 20698363
TI  - [The North African plague and Charles Nicolle's theory of infectious diseases].
AB  - Many infectious diseases were described in North Africa in 18th-19th centuries by
      European travellers. Most of them were allegedly imported by new migrant
      populations coming from sub-Saharan, European or Middle East countries. Plague
      outbreaks have been described since the Black Death as diseases of the
      Mediterranean harbours. Charles Nicolle and his collaborators at the Pasteur
      Institute were witnesses to the extinction of plague and typhus fever in Tunisia.
      Both could be considered as endemo-epidemic diseases propagated by ancient nomad
      communities for centuries. Typhus was exported to other countries; plague was
      imported by Mediterranean travellers but also hid in unknown wild-animal
      reservoirs. The role of the bite of a rat's flea was not confirmed and the
      pneumonic form might have prevailed in the medieval North African cities.
      Association between plague, typhus, flu and other causes of immune deficiencies
      could explain the high morbidity and mortality caused by plague in the past. The
      authors comment the local history of plague at the light of the evolutionary laws
      of infectious disease proposed by Charles Nicolle in 1930.

PMID- 20698364
TI  - [A difficult stabilisation. Chlorpromazine in the fifties in Belgium].
AB  - Through a Belgian case study the article tries to trace the gradual stabilisation
      of chlorpromazine as an antipsychotic in the 1950s. By varying ranges and angles
      of approach it shows the heterogeneity of actors involved and the semantic
      bricolage that accompany the marketing of the first antipsychotic. Far from being
      a revolution, the presence of Largactil in psychiatric practice is rather
      characterised by integration into a wider range of medicines and sinuous
      searching to give sense to this new drug.

PMID- 20698365
TI  - [Psychological events--organic interpretations: concepts of trauma in German
      psychiatry since 1889].
AB  - This paper examines the debate on psychological trauma in German psychiatry since
      1889. A content analysis of five leading German psychiatric journals between 1889
      and 2005 is realised. An organic concept of psychological trauma has been
      prominent in the professional debate until today. Psychiatrists frequently
      referred to physical traumatisation, constitutional factors and genetic
      predisposition, exogenous reaction types according to Bonhoeffer, and to
      biological markers in the context of the PTSD concept. The biological tradition
      in German psychiatry resulted in a specific adoption of concepts on psychological
      trauma. However, integrating various models of psychological trauma into a
      psychiatric tradition focusing on a biological model proved to be difficult and
      inconsistent.

PMID- 20698366
TI  - [Ancient psychopathology: sources, historiography and perspectives].

PMID- 20698367
TI  - Current status of surgical techniques for parathyroidectomy for untreated primary
      hyperparathyroidism: is the technology worth it?

PMID- 20698368
TI  - History of the Georgia Baptist/Atlanta Medical Center surgical residency.
AB  - The Georgia Baptist Hospital established itself as a premier healthcare facility
      during the first 50 years of the 20th century. The surgical residency started in
      the 1940s, became accredited in 1958, and has grown into one of the most
      respected independent programs in the country. The development and growth of the
      program was a result of the commitment and dedication of the Program Directors in
      Surgery over the past 50 years. These key leaders included A. Hamblin Letton,
      John P. Wilson, Paul Stanton, and George Lucas. The hospital's name has changed
      to Atlanta Medical Center with the sale of the hospital to Tenet in 1997. The
      same old school approach to surgical training that characterized the residency
      when it was known as Georgia Baptist persists and provides outstanding training
      for future surgeons interested in a broadly based surgical education and
      experience.

PMID- 20698369
TI  - Second primary melanomas: incidence and outcome.
AB  - The objective of this study was to determine the incidence of multiple primary
      melanomas (MPM) and other cancers types among patients with melanoma. Factors
      associated with development of MPM were assessed in a post hoc analysis of the
      database from a multi-institutional prospective randomized trial of patients with
      melanoma aged 18 to 70 years with Breslow thickness 1 mm or greater. Disease-free
      survival (DFS) and overall survival (OS) were evaluated by Kaplan-Meier analysis.
      Forty-eight (1.9%) of 2506 patients with melanoma developed additional primary
      melanomas. Median follow-up was 66 months. Except in one patient, the subsequent
      melanomas were thinner (median, 0.32 mm vs. 1.50 mm; P < 0.0001). Compared with
      patients without MPM, patients with MPM were more likely to be older (median age,
      54.5 vs. 51.0 years; P = 0.048), to have superficially spreading melanomas (SSM)
      (P = 0.025), to have negative sentinel lymph nodes (P = 0.021), or to lack
      lymphovascular invasion (LVI) (P = 0.008) with the initial tumor. On multivariate
      analysis, age (P = 0.028), LVI (P = 0.010), and SSM subtype of the original
      melanoma (P = 0.024) were associated with MPM. Patients with MPM and patients
      with single primary melanoma had similar DFS (5-year DFS 88.7 vs. 81.3%, P =
      0.380), but patients with MPM had better OS (5-year OS 95.3 vs. 80.0%, P =
      0.005). Nonmelanoma malignancies occurred in 152 patients (6.1%). Ongoing
      surveillance of patients with melanoma is important given that a significant
      number will develop additional melanoma and nonmelanoma tumors. With close follow
      up, second primary melanomas are usually detected at an early stage.

PMID- 20698370
TI  - After-hours complications: evaluation of the predictive accuracy of resident sign
      out.
AB  - Resident duty-hour restrictions demand effective communication and teamwork in
      patient care. The process of resident sign-out is a potential source of
      miscommunication and medical error. Resident sign-out was followed over a 3-month
      period. Residents signing out to the night coverage team were asked to identify
      two patient groups: (1) problem patients who were especially ill and likely to
      present specific clinical problems; and (2) nonproblem patients who were likely
      not to be at risk for a problem requiring attention. Data on adverse events
      collected by the night float resident were classified into three categories: a
      problem predicted during sign-out in a problem patient, an unpredicted problem on
      a problem patient, and an unpredicted problem on all other patients. Resident
      sign-out accurately predicted only 42 per cent of adverse events. Only one third
      of major adverse events were predicted at checkout. One third of events occurred
      in patients identified at sign-out as being in the nonproblem group. The process
      of transfer of care must be standardized and individual practices reviewed to
      prevent error. Instruction on proper transfer of care and illustrations of
      potential points of breakdown should be given for all levels of training.

PMID- 20698371
TI  - Small bowel obstruction: outcome and cost implications of admitting service.
AB  - We compared patients with small bowel obstruction (SBO) admitted through the
      emergency department to the surgical service (SS) with those admitted to the
      medical service (MS) with respect to outcomes and healthcare cost. We conducted a
      retrospective analysis of our SBO database comparing 482 patients admitted to SS
      and 153 patients admitted to MS at a single institution over a 5-year period
      (January 2003 to December 2007). Study outcomes included length of hospital stay
      (LOS), time to surgery (TTS), hospital charges, incidence of bowel resection, and
      mortality. Both groups were comparable for age, gender, and race. The SS group
      had a shorter LOS (6.1 vs. 7.5 days; P = 0.01), less hospital charges ($29,549
      vs. $35,789; P = 0.06), shorter TTS (log rank comparison; P = 0.006), and less
      mortality (eight [1.66%] vs. six [3.92]; P = 0.11). The SS group had more bowel
      resections (13.1 vs. 5.2%; P = 0.007). Coronary artery disease (CAD), acute renal
      failure (ARF), admission to SS, and female gender were significant predictors of
      bowel resection. CAD and ARF were significant predictors of mortality. Two
      hundred forty-four patients required operative intervention (surgery operative
      subgroup [SOS] 210 [43.6%], medicine operative subgroup [MOS] 34 [22.2%]). SOS
      and MOS were comparable for gender and race. SOS had shorter LOS (9.1 vs. 12.3
      days; P = 0.02), less hospital charges ($46,258 vs. $62,778, P = 0.05), and less
      mortality (eight [3.81%] vs. four [11.76%]; P = 0.07). Bowel resection was
      comparable (SOS 30% vs. MOS 23%; P = 0.44). CAD and congestive heart failure
      (CHF) were significant predictors of bowel resection, whereas CAD was the only
      significant predictor of mortality in this subgroup. We recommend that patients
      with SBO be admitted to SS because this might translate to shorter LOS, earlier
      operative intervention, and reduced healthcare use direct cost. Bowel resection
      and death are more likely to occur in patients with comorbidities like CHF, CAD,
      diabetes mellitus, and ARF.

PMID- 20698372
TI  - Free and local continuing medical education does not guarantee surgeon
      participation in maintenance of certification learning activities.
AB  - The American Board of Surgery has adopted the Maintenance of Certification
      requirement for surgeons. It requires continuous professional development (CPD)
      using active and passive learning modalities in contrast to traditional
      continuing medical education (CME). The Rural Trauma Team Development Course
      developed by the American College of Surgeons Committee on Trauma is a CPD
      learning activity. We provided 22 free courses between May 2007 and June 2009 to
      trauma care providers at 11 affiliated community and critical access hospitals.
      The course was taught on-site by an interdisciplinary group and at least one
      trauma surgeon was faculty. Free Category I CME credits and continuing education
      units were provided. Two hundred thirty-four providers attended and the majority
      were RNs (60%) and emergency medical technicians (21.8%). Only 18 were physicians
      (7.7%) and none were surgeons. The majority felt that they would change their
      practice as a result of the course but cited the lack of attendance at the course
      by emergency physicians and surgeons as a deficit. It may be that surgeons have
      barriers such as time away from a practice to attending these newer types of
      educational opportunities. Those who develop and offer these courses may need to
      develop different strategies to reach this target audience.

PMID- 20698373
TI  - The effect of diabetes mellitus on surgical site infections after colorectal and
      noncolorectal general surgical operations.
AB  - Patients undergoing colorectal surgery (CRS) are known to be at increased risk of
      surgical site infection (SSI). We assessed the effect of diabetes and other risk
      factors on SSI in patients undergoing CRS and patients undergoing general surgery
      (GS). American College of Surgeons National Surgical Quality Improvement Program
      Participant Use Data File from 2005 to 2006 was used. Chi2 tests, t tests, and
      logistic regression were used to assess the risk factors. Of the 129,909 study
      patients 10.1 per cent were patients undergoing CRS. The incidence of SSI in
      patients undergoing CRS was 3.8 times higher (95% CI, 3.6-4.1) than in patients
      undergoing GS. The incidence of SSI was higher in diabetics than nondiabetics in
      patients undergoing CRS (15.4 vs. 11.0%, P < 0.001) and patients undergoing GS
      (5.3 vs. 3.1%, P < 0.001). The significant univariate predictors of SSI for
      patients undergoing GS and patients undergoing CRS were: males, American Society
      of Anesthesiologists (ASA) class, diabetes emergency surgery, operation time, and
      greater than 2 units of intraoperative red blood cell transfusion. For patients
      undergoing GS, increasing age was also significant. After multivariate
      adjustment, significant predictors of SSI for patients undergoing GS and patients
      undergoing CRS were: male gender, diabetes, ASA class, emergency surgery, and
      operation time. For patients undergoing GS, age also remained significant. Among
      patients undergoing CRS, insulin-dependent diabetes mellitus (IDDM) and
      noninsulin-dependent diabetes mellitus (NIDDM) were 1.32 (P < 0.05) times more
      likely than nondiabetics to develop SSI. Among patients undergoing GS, only IDDM
      (OR, 1.39; P < 0.001) were at increased risk. In this large hospital-based study,
      patients undergoing CRS were three times more likely to get SSI than patients
      undergoing GS. Diabetic patients with CRS (IDDM and NIDDM) and patients
      undergoing GS (IDDM) were at increased risk of SSI compared with nondiabetics.
      More intense glycemic control may reduce SSI in patients undergoing CRS with
      diabetes.

PMID- 20698374
TI  - Initial experience with single-incision laparoscopic cholecystectomy.
AB  - Single-incision laparoscopic surgical procedures are being developed with the
      goal of improving cosmesis, reducing postoperative pain, and increasing patient
      satisfaction. We performed this study to evaluate our initial experience with
      single-incision laparoscopic cholecystectomy. We used an infraumbilical incision
      with two upper low-profile 5-mm ports and one lower standard 5-mm port and either
      a standard 30 degrees Storz laparoscope or an Olympus deflectable tip
      laparoscope. All patients were followed postoperatively to evaluate the
      feasibility and outcomes of the procedure. A total of 60 gallbladders were
      successfully removed by this method (95.2% success rate). Three cases were
      converted to standard laparoscopic cholecystectomy (4.8% conversion rate) with no
      conversion to open cholecystectomy. There were no major complications (bile duct
      injury, liver injury, bowel injury, biliary leak). Median operative time was 51
      +/- 21 minutes. Diagnoses included cholelithiasis (55%), biliary dyskinesia
      (32%), biliary colic (13%), and one case of gangrenous cholecystitis. Median
      patient age was 47 years with a strong female predominance (87%). Our initial
      experience demonstrates that single-incision laparoscopic cholecystectomy is
      effective and safe. We are confident that single-incision laparoscopic
      cholecystectomy is a viable alternative to standard laparoscopic cholecystectomy.

PMID- 20698375
TI  - Management of acute cholecystitis in critically ill patients: contemporary role
      for cholecystostomy and subsequent cholecystectomy.
AB  - The diagnosis of acute cholecystitis in critically ill patients carries a high
      mortality rate. Although decompression and drainage of the gallbladder through a
      cholecystostomy tube may be used as a temporary treatment of acute cholecystitis
      in this population, there is still some debate about the management of the tube
      and the subsequent need for a cholecystectomy. This series evaluates the clinical
      course and outcomes of critically ill patients who underwent the insertion of
      cholecystostomy tubes for the initial treatment of acute cholecystitis. This is a
      retrospective review of critically ill patients admitted to the hospital
      intensive care unit who were diagnosed with acute cholecystitis and underwent a
      cholecystostomy tube as a temporary treatment for the disease. Patients were
      identified through the Greenville Hospital System electronic medical records
      coding database. Medical records were reviewed for demographic data, diagnoses,
      imaging, complications, and outcomes. From January 2002 through June 2008, 50
      patients were identified for the study. The mean age was 72 +/- 11 years, and the
      majority (66%) were men. The following comorbidities were found: severe
      cardiovascular disease (40 patients), respiratory failure (30 patients), and
      multisystem organ dysfunction (30 patients). The mean intensive care unit length
      of stay (LOS) was 16 +/- 9 days, and the mean hospital LOS was 28 +/- 27 days. At
      30 days, the morbidity associated with the cholecystostomy tube itself was 4 per
      cent, but overall in-hospital morbidity and mortality rates were 62 and 50 per
      cent, respectively. Of the 25 patients who survived longer than 30 days, 12
      retained their cholecystostomy tubes until they underwent cholecystectomy (four
      open, seven laparoscopic). All of the remaining 13 patients had their
      cholecystostomy tubes removed, and eight developed recurrent cholecystitis. Of
      these patients with recurrent of cholecystitis, five had cholecystectomy or
      repeat cholecystostomy, but the remaining three patients died. Although this is a
      small patient population, these data suggest that, in critically ill patients,
      cholecystostomy tubes should remain in place until the patient is deemed
      medically suitable to undergo cholecystectomy. Removal of the cholecystostomy
      tube without subsequent cholecystectomy is associated with a high incidence of
      recurrent cholecystitis and devastating consequences.

PMID- 20698376
TI  - Vena cava filter insertion and the general surgery armamentarium: a 13-year
      experience.
AB  - The prevention of pulmonary emboli has a long surgical history. Through the
      development of percutaneous technologies, vena cava filters (VCFs) are now
      commonly inserted by interventional radiologists. This study reviews our
      experience with VCFs inserted by general surgeons. We retrospectively reviewed
      data from our VCF performance improvement database, which is a prospective
      collection of the VCF experience of the Department of General Surgery from
      February 1996 to May 2009. Demographics, procedural information, and
      complications were recorded. Eight hundred fifty-five VCFs were inserted in 853
      patients. The mean age was 42.0 years (range, 14 to 90 years). One hundred ninety
      seven VCFs were placed in the operating room, and 658 were placed in the
      intensive care unit. Twelve VCFs were intentionally inserted in a suprarenal
      position, and four were placed in the superior vena cava. Two patients received
      both superior vena cava and inferior vena cava filters. Complications included
      deep vein thrombosis at the insertion site (n=16), vena cava thrombosis (n=9),
      post-VCF pulmonary embolism (n=2), and a ventricle perforation requiring
      operative repair (n=1). No deaths were attributed to the presence of a VCF.
      Overall insertion success was 99.8 per cent. In two patients, an inferior VCF
      could not be placed as a result of inferior vena cava occlusion with no safe
      "landing zone" for deployment. The placement of VCFs is a vital skill in the
      general surgery armamentarium. Our experience demonstrates that general surgeons
      can safely insert VCFs with minimal perioperative complications.

PMID- 20698377
TI  - Rectosigmoid intussusception through the anus mimicking rectal prolapse.
AB  - Intussusception of the colon usually occurs in infants and children. Although
      rectal prolapse is not uncommon, presentation of more proximal segments of large
      bowel through the anus is extremely rare. We report two cases of rectosigmoid
      intussusception in which sigmoid colon intussusception was diagnosed as rectal
      prolapse preoperatively.

PMID- 20698378
TI  - Pulmonary contusion in the pediatric population.
AB  - Pulmonary contusion in the adult population is an independent risk factor for
      respiratory failure, ventilator associated pneumonia, and acute respiratory
      distress syndrome. Pilot studies in adults note an increased risk when volume of
      pulmonary contusion exceeds 20 per cent of total lung volume. The purpose of this
      study was to determine if children with pulmonary contusion suffer the same
      morbidity as adults. From January 2005 to May 2007, all trauma patients ages 3 to
      18-years-old were assessed for CT evidence of pulmonary contusion. Children were
      excluded if injury included confounding variables, which could result in
      respiratory failure independent of contusion status. CT images were reviewed and
      pulmonary contusion was calculated as a percentage of total lung volume. Outcomes
      including need for invasive ventilation, pneumonia, and development of
      oxygenation problems were recorded. Data collected included patient age, Injury
      Severity Score, arterial blood gas findings, and number of rib fractures. Twenty
      six patients met criteria for the study with a mean age of 13.35 years and mean
      Injury Severity Score of 24. The mean percentage of pulmonary contusion was 19.81
      per cent. No patients required intubation. Pediatric pulmonary contusion does not
      carry the same morbidity as noted in the adult population. Invasive airway
      management is rarely required.

PMID- 20698379
TI  - Pancreatic cyst: pseudocyst or neoplasm? Pitfalls in endoscopic retrograde
      cholangiopancreatography diagnosis.
AB  - Pancreatic pseudocysts represent the majority of cystic lesions, and can usually
      be differentiated from cystic neoplasms, which have malignant potential.
      Endoscopic retrograde cholangiopancreatography (ERCP) can help in solving
      diagnostic dilemmas. When ERCP demonstrates cyst communication with the
      pancreatic duct, the diagnosis of pseudocyst is usually secure. There are
      exceptions, however, as reported in these two case reports. A retrospective chart
      review was conducted of two patients undergoing distal pancreatectomy in 2008 to
      2009 for cystic lesions communicating with the main pancreatic duct on ERCP. Both
      patients were women (ages 37 and 42) with a history of chronic abdominal pain and
      pancreatitis. Radiologic imaging showed cystic lesions in the pancreatic tail.
      ERCP demonstrated main pancreatic duct communication. When endoscopic management
      failed, surgical therapy was undertaken. Both patients underwent distal
      pancreatectomy with splenectomy. Pathologic findings were mucinous cystadenoma.
      The conventional wisdom that a pancreatic cyst communicating with the main
      pancreatic duct is a benign pseudocyst is not always wise. As seen in this
      series, mucinous cystadenomas can erode into the main pancreatic duct. Women in
      the fourth and fifth decade with symptomatic cysts in the pancreatic tail with a
      history of pancreatitis should undergo distal pancreatectomy, regardless of
      ductal communication on ERCP.

PMID- 20698380
TI  - Review of re-excision for narrow or positive margins of invasive and intraductal
      carcinoma.
AB  - The trend in breast surgery has shifted towards breast conservation. Re-excision
      rates for narrow or positive margins have been variable in published reports. A
      retrospective analysis of 3246 patients who underwent either a lumpectomy for a
      palpable mass or a needle localization biopsy between January 2003 and December
      2007 was done. Five hundred and eighty-five patients underwent re-excision
      surgery for margins. The mean patient age was 59-years-old (range 25-93). Needle
      localization was used to guide initial excision in 372 of 585 patients (64%).
      Invasive carcinoma was seen in 402 (69%) patients, ductal carcinoma in situ
      (DCIS) alone in 183 (31%) patients, and 308 (53%) patients had both invasive
      carcinoma and DCIS. Well-differentiated carcinomas accounted for only 24 per cent
      of the re-excisions. Four hundred and sixteen patients underwent re-excision of
      margins, whereas 169 underwent mastectomy as the second surgery. Residual
      carcinoma was seen in 38 per cent of cases with involved margins, as compared
      with 24 per cent with <1 mm margins and only 12 per cent cases with >1 mm
      margins. Residual DCIS was seen in 65 per cent with involved margins, 50 per cent
      with <2 mm margins, and 35 per cent of cases with 2 to 5 mm margins (P < 0.001,
      chi2 association). Lesser re-excision was noted in well-differentiated invasive
      carcinomas. Only 12 per cent of patients with margins greater than 1 mm had
      residual tumor on re excision, which raises the possibility of nonoperative
      management in such cases.

PMID- 20698381
TI  - Initial institutional experience with thoracoscopic assisted esophagectomy.
AB  - We report our initial experience with thoracoscopic assisted esophagectomy (TAE)
      in patients with esophageal carcinoma. Clinical outcome measures are reported for
      14 consecutive patients who underwent thoracoscopically assisted esophagectomy at
      our institution between January 2007 and June 2009. These outcomes were compared
      with 18 patients who underwent open esophagectomy (OE) during this time. All 14
      patients were male, with a median age of 63. All had distal esophageal
      adenocarcinoma: stage I (7), II A (2), II B (3), and III (2). Surgical approaches
      included laparotomy combined with thoracoscopy and cervical (n=12), or
      intrathoracic anastomosis (n=2). Compared with an open approach, the
      thoracoscopic assisted esophagectomies were longer (median time 460 vs. 386
      minutes), and they were associated with less blood loss (250 mL vs. 500 mL) and
      less respiratory complications (14.3% vs. 27.8%). In our TAE group more lymph
      nodes were removed (median number 12 in TAE vs. 10 in OE). The overall morbidity
      was similar in both groups (42.8% in TAE vs. 50% in OE group), but the in
      hospital mortality was reduced with TAE (7.1% with TAE vs. 16.7% with OE). TAE is
      feasible with a low conversion rate, acceptable morbidity, and low mortality.

PMID- 20698382
TI  - Improving participation and quality of clinical research in a university-based
      general surgery residency program.
AB  - At a university-based general surgery training program, post-graduate year (PGY)
      to 5 categorical general surgery residents had been required to complete an
      annual clinical research project and a year of laboratory research. Since the 80
      hour work week, the laboratory experience was made optional, with a resultant
      decline in laboratory and clinical participation by 50 per cent and 75 per cent,
      respectively. Our goal was to review the effect of a simple programmatic
      intervention on the research compliance rate and quality. The Department was
      informed about the clinical research requirement via e-mail, memo, and
      announcements. Faculty submitted lists of novel or on-going projects. This was
      compiled and e-mailed to the Department with a list of project milestones. This
      included identification of a research mentor and project, Human Subjects Course
      certification, institutional review board submission dates, a midyear progress
      report, and final submission date. Rates of compliance and nature of research
      were recorded the year before and the 2 years after the intervention. Before the
      intervention, 2 of 16 residents were compliant. Faculty submitted 76 projects for
      resident review. One hundred per cent compliance with all aspects of the program
      was seen at the end of both year 1 and 2. Case reports rate fell from 65, to 30,
      to 25 per cent by the end of year 2. Publications increased from three
      preintervention to 13 by year 2. Presentations increased from five
      preintervention to 13 by end of year 2. This study demonstrates that small
      inexpensive interventions can have a dramatic effect on research participation.

PMID- 20698383
TI  - Retention of colonoscopy skills after virtual reality simulator training by
      independent and proctored methods.
AB  - Virtual reality (VR) simulators may enhance surgical resident colonoscopy skills,
      but the duration of skill retention and the effects of different simulator
      training methods are unknown. Medical students participating in a randomized
      trial of independent (automated simulator feedback only) versus proctored (human
      expert feedback plus simulator feedback) simulator training performed a
      standardized VR colonoscopy scenario at baseline, at the end of training
      (posttraining), and after a median 4.5 months without practice (retention).
      Performances were scored on a 10-point scale based on expert proficiency criteria
      and compared for the independent and proctored groups. Thirteen trainees (8
      proctored, 5 independent) were included. Performance at retention testing was
      significantly better than baseline (median score 10 vs. 5, P < 0.0001), and no
      different from posttraining (median score 10 vs. 10, P = 0.19). Score changes
      from baseline to retention and from posttraining to retention were no different
      for the proctored and independent groups. Overinsufflation and excessive force
      were the most common reasons for nonproficiency at retention. After proficiency
      based VR simulator training, colonoscopy skills are retained for several months,
      regardless of whether an independent or proctored approach is used. Error
      avoidance skills may not be retained as well as speed and efficiency skills.

PMID- 20698384
TI  - Outcomes of low anterior resection anastomotic leak after preoperative
      chemoradiation therapy for rectal cancer.
AB  - Anastomotic leak remains a major cause of morbidity and mortality after
      colorectal surgery, especially with low anastomoses. The aim of this study was to
      assess outcomes of patients who developed an anastomotic leak after low anterior
      resection of the rectum for rectal cancer. An Institutional Review Board-approved
      retrospective review of 89 consecutive patients undergoing open low anterior
      resection with primary anastomosis for cancer of the mid/lower rectum at a single
      institution between January 2001 and December 2008 was performed. All patients
      received neoadjuvant chemotherapy and radiation therapy. Proximal diversion was
      performed in all patients. Perioperative data were collected and analyzed with
      attention to management and outcomes after development of anastomotic leak. Nine
      patients (10.1%) developed anastomotic leak. Mean age was 62 years. Mean tumor
      level was 4.8 cm above the anal verge. Symptomatic anastomotic leak developed in
      seven (78%) patients. Percutaneous drainage was performed in five (55.6%)
      patients with an average of 4.4 procedures required for management of anastomotic
      leak. Five (55.6%) patients required reoperation. Only two procedures (25%)
      involved laparotomy. No operative procedures were performed emergently. There
      were no mortalities. Excluding one patient who received completion proctectomy
      for local recurrence, restoration of intestinal continuity was achieved in five
      (63%) of eight patients. Mean time to stoma closure was 289 days. The potentially
      lethal complication of anastomotic leak after low anterior resection for rectal
      cancer can be managed expectantly and electively in patients who are proximally
      diverted with the expectation of stoma reversal in the long term.

PMID- 20698385
TI  - Bilateral gluteal compartment syndrome: a rare but potentially morbid entity.
AB  - Compartment syndrome is caused by elevated interstitial pressure within the
      myofascial compartment. It rarely presents bilaterally in the gluteal region. A
      49-year-old man fell 10 feet from a roof on his buttocks. He presented 10 hours
      after the injury with intense lumbar pain. Both glutei were exceptionally tense.
      There were no vascular injuries or sensory deficits. Compartmental pressures
      measured 60 mm Hg on the left side and 50 mm Hg on the right side. The patient
      was taken to the operating room for decompressive fasciotomy. The glutei
      compartments were released. He was taken once more to the operating room,
      requiring only minimal debridement. He was discharged the next week with no
      neurological deficit. Bilateral gluteal compartment syndrome is very rare with
      few cases reported in the literature. It has been associated with trauma,
      prolonged recumbence, surgical instrumentation, and illicit drug abuse. Early
      recognition is required to avoid the potential severe metabolic and physical
      deficits.

PMID- 20698386
TI  - An evaluation of snake bites and antivenin use at a regional medical center.
AB  - Snake bites are a rare but challenging problem for surgeons. The purpose of our
      study was to evaluate our experience with snake bites at a regional medical
      center. We reviewed patients treated for snake bites from 2004 to July 2008.
      Demographics, clinical information, and outcomes were documented. Descriptive
      statistics were used, and chi2, t test, and Fisher exact test were used to
      compare patients based on antivenin use. A P value < 0.05 was considered
      significant. Over the study period, 126 patients presented to the emergency
      department with 44 (35%) requiring hospital admission. The average age was 38
      years (range, 2 to 76 years); 66 per cent were male and 95 per cent white. Bites
      most commonly occurred in the summer and fall months with none from December
      through March. Copperhead bites accounted for 50 per cent of bites. An average of
      4.8 vials of antivenin was given to 61 per cent of admitted patients with 93 per
      cent receiving the drug within 6 hours. Minor reactions to antivenin occurred in
      three patients (11%). Two patients required surgery (5%), and the readmission
      rate was 7 per cent. There was no known morbidity or mortality. When comparing
      patients who received antivenin with patients who did not, the only significant
      clinical variables were an increased prothrombin time (12.1 vs. 11.7,
      respectively; P = 0.048) and a longer length of hospital stay (3 vs. 1.8 days, P
      = 0.0006) in patients receiving antivenin. The majority of patients with snake
      bites can be treated with supportive care and antivenin when indicated. Antivenin
      use at our institution is largely based on physical findings and not related to
      laboratory values.

PMID- 20698387
TI  - Gastrointestinal carcinoids: an increasing incidence of rectal distribution.
AB  - Carcinoid tumors are slow-growing and usually become symptomatic late in the
      course of the disease. We evaluated our 10-year experience in the management of
      GI carcinoid tumors. The records of 133 patients with GI carcinoids were
      reviewed. The rectum was the most common site for carcinoid tumors with an
      incidence of 30 per cent followed by jejunoileal at 29.3 per cent. Other sites of
      carcinoid tumors were the appendix (8.3%), colon (8.3%), and duodenum (3.8%).
      Endoscopy was the most helpful modality in diagnosing GI carcinoids. CT was not
      helpful in preoperative diagnosis of carcinoid tumor. Fifteen patients died in
      follow-up with eight deaths related to carcinoid tumors, in the small bowel (6),
      rectum (1), and colon (1). Overall survival was 68.7 per cent and mortality rate
      was 19.5 per cent from carcinoid tumors. Most of the deaths occurred in patients
      with carcinoid syndrome, synchronous malignancy, and malignant carcinoid tumors.
      The mean disease-free survival was 51 months (range, 15 to 138 months). Screening
      colonoscopy, in addition to decreasing colorectal adenocarcinoma mortality, is
      useful in diagnosing carcinoid tumors at an earlier stage and in decreasing
      mortality from malignant colorectal carcinoid tumors.

PMID- 20698388
TI  - A minor modification of Lichtenstein repair of primary inguinal hernia:
      postoperative discomfort evaluation.
AB  - The aim of this study was to evaluate the usefulness of a modification of the
      Lichtenstein hernioplasty procedure by evaluating its impact on postoperative
      discomfort. From December 1999 to May 2006, the Lichtenstein inguinal
      hernioplasty was performed in 406 patients with noncomplicated unilateral
      inguinal hernia. During reconstruction, the mesh was fixed to the inguinal canal
      floor without stitching its upper margin to the internal oblique muscle. Control
      of postoperative pain proved to be satisfactory; 72 hours after surgery, 26.1 per
      cent of patients no longer felt any pain, whereas 54.4 per cent had slight pain
      without the need for painkillers; on Day 7, 92.8 per cent felt no pain at all.
      After 10 days, 86.7 per cent of those with sedentary jobs were able to return to
      work, whereas 79.1 per cent of those with heavier jobs resumed work in 11 to 15
      days. Our modification of the original Lichtenstein procedure permitted us to
      obtain satisfactory results with regard to the control of postoperative chronic
      pain and a rapid reprisal of normal working activity.

PMID- 20698389
TI  - Endovascular aortic repair of infrarenal abdominal aortic dissection.
AB  - We present two cases of infrarenal abdominal aortic dissection (IAAD) that were
      treated by endovascular aortic repair (EVAR). The EVAR procedure was successful,
      although one patient developed a proximal Type I endoleak several months after
      the procedure; both patients remain symptom-free more than 24 months after
      surgery. A literature search revealed that EVAR has been performed in only 14
      cases of IAAD. Based on these 14 cases, we believe EVAR is feasible and effective
      for the treatment of IAAD. Moreover, this treatment strategy represents a
      reasonable alternative to open surgery, especially in cases of complicated
      juxtarenal abdominal aortic dissection.

PMID- 20698390
TI  - Surgical application of kaolin-impregnated gauze (Combat Gauze) in severe
      hemorrhagic gastritis.

PMID- 20698391
TI  - Thoracic outlet syndrome after contralateral-sided mastectomy in a patient with
      breast cancer.

PMID- 20698392
TI  - Multi-modality therapy for metastatic colorectal cancer-ready for prime time?

PMID- 20698393
TI  - Laparoscopic resection of an intra-abdominal pulmonary sequestration.

PMID- 20698394
TI  - Common duct obstruction by shotgun bullet fragment as a cause of cholangitis.

PMID- 20698395
TI  - Giant midthoracic pulsion diverticulum of the esophagus.

PMID- 20698396
TI  - Axillary artery thrombosis in a newborn: recovery with surgical therapy.

PMID- 20698397
TI  - Skin sparing mastectomy with delayed implant reconstruction.

PMID- 20698398
TI  - Oesophagical duplication cyst: thoracoscopic resection.

PMID- 20698399
TI  - Pedicled jejunal patch duodenoplasty for traumatic duodenal injury: report of a
      successfully treated case.

PMID- 20698400
TI  - The social identity of hospital consultants as managers.
AB  - PURPOSE: This paper aims to explore hospital consultants' social identification,
      in terms of perceptions of their position in society, the salient targets for
      their social identification and how this appears to influence their perceptions
      of management activities and change. DESIGN/METHODOLOGY/APPROACH: A purposeful
      sample of 15 hospital consultants from a wide range of specialities and work
      locations in Ireland were recruited. Semi-structured, in-depth interviews were
      undertaken and thematic analysis was used to interpret the interview data.
      FINDINGS: The paper finds that all interviewees perceived public attitudes
      towards hospital consultants, as a group, to be negative. Twelve interviewees
      derived most sense of belonging from group membership within their immediate work
      area. These groups seemed to represent sources of validation and esteem and
      enabled consultants to exercise control over their work. Many consultants,
      however, described a sense of detachment from their employing health boards.
      Management, as a salient target for social group identification, was perceived as
      associated with powerlessness and lack of respect. Interviewees generally viewed
      involvement in management with little enthusiasm and considerable caution.
      PRACTICAL IMPLICATIONS: This paper shows that management approaches to hospital
      consultants could benefit from awareness that their social identity may already
      be under threat. Assaults on core professional values in the communication
      surrounding change are likely to provoke resistance. Existing work groups, with
      which consultants identify, could serve as a less threatening means to engage
      them with issues of cost and quality than externally imposed structures.
      ORIGINALITY/VALUE: This paper informs ways in which hospital consultants could be
      more successfully involved in health service management.

PMID- 20698401
TI  - International medical graduates in Australian news: a media narrative analysis.
AB  - PURPOSE: The paper aims to analyse how the medical profession, the pro
      competition organisation, and the rural community have responded to the rural
      doctor shortage with reference to international medical graduates (IMGs) as
      reported in Australian newspapers. DESIGN/METHODOLOGY/APPROACH: Utilising the
      commercially available database LexisNexis during 2003, the author keyed in
      "overseas trained doctors" and retrieved 641 Australian newspaper articles. The
      qualitative data analysis software NVivo2 has assisted the author to organise the
      data, informed by critical realism and narrative analysis. FINDINGS: While the
      medical profession is undoubtedly committed to serving the health needs of the
      Australian public, the medical community is less than united in addressing the
      rural doctor shortage, especially through the employment of large numbers of
      IMGs. The handling of IMGs has led to tensions not only between the locally
      trained and IMGs, but also between rural and non-rural doctors, and between
      younger and established doctors. The medical professional institutions seemed
      relatively detached from the adverse consequences of the shortage of doctors in
      the rural community. This contrasts the efforts demonstrated by the Rural Doctors
      Association and the rural community. ORIGINALITY/VALUE: This paper concludes with
      a critical realist and narrative analysis and resolving of the rural doctor
      shortage and recommends close communication and consultation among the diverse
      interest groups rather than their engaging in blaming one another. This would be
      an obvious starting point to address the rural doctor shortage, which may partly
      be achieved by the effective use of services by IMGs.

PMID- 20698402
TI  - Leadership in health care: developing a post-merger strategy for Europe's largest
      university hospital.
AB  - PURPOSE: This paper's aim is to identify existing and developing new concepts of
      organization, management, and leadership at a large European university hospital;
      and to evaluate whether mixed qualitative-quantitative methods with both internal
      and external input can provide helpful views of the possible future of large
      health care providers. DESIGN/METHODOLOGY/APPROACH: Using the Delphi method in
      semi-structured, semi-quantitative interviews, with managers and employees as
      experts, the authors performed a vertical and a horizontal internal analysis. In
      addition, input from innovative faculties in other countries was obtained through
      structured power questions. These two sources were used to create three final
      scenarios, which evaluated using traditional strategic planning methods.
      FINDINGS: There is found a collaboration scenario in which faculty and hospital
      are separated; a split scenario which divides the organization into three
      independent hospitals; and a corporation scenario in which corporate activities
      are bundled in three separate entities. PRACTICAL IMPLICATIONS: In complex
      mergers of knowledge-driven organizations, the employees of the own organization
      (in addition to external consultants) might be tapped as a knowledge resource to
      successful future business models. ORIGINALITY/VALUE: The paper uses a real world
      consulting case to present a new set of methods for strategic planning in large
      health care provider organizations.

PMID- 20698403
TI  - The ethics of data collection: unintended consequences?
AB  - PURPOSE: The aims is to consider the political and ethical challenges involved in
      conducting ethnographic managerial/organisational behaviour research within the
      highly regulated health and social care context, in light of the emergence of
      more stringent "ethical approval" policies and requirements set by Local Research
      Ethics Committees in the United Kingdom. In the attempt and requirement to
      protect "vulnerable" employees, this paper aims to present an unintended paradox
      of consequences when participants voluntarily revealed themselves.
      DESIGN/METHODOLOGY/APPROACH: The authors briefly review literature on research
      ethics and present an understanding of the ethical regulations currently existing
      within the British National Health Service. Within an ethnographic case study
      exploring the psychological contract, the authors consider the issues that arose
      during one stage of data collection: a qualitative questionnaire survey with 13
      participants, including members of the lead author's team. Incorporating excerpts
      from the researcher's reflexive journal, the paper exposes the struggles of being
      an "insider" researcher and the tensions this raises for data analysis when
      participants voluntarily revealed themselves. FINDINGS: Ethnography is at "risk"
      within health and social care and ethnographic "managerial" research is likely to
      be unduly restricted and potentially threatened. The evidence suggests that some
      employees either did not wish to be protected or, conversely, felt compelled to
      reveal their identities, raising questions of their motivation and creating a
      paradox of unintended consequences. ORIGINALITY/VALUE: This paper offers an
      insight into the challenges of conducting nurse-managerial ethnography in
      compliance with ethical guidelines, yet disrupted by participants. The findings
      will be useful to other nurse-researchers attempting to conduct insider research.

PMID- 20698404
TI  - Medical assistants: the invisible "glue" of primary health care practices in the
      United States?
AB  - PURPOSE: Little attention has been given to the field of medical assisting in US
      health services to date. To explore the roles medical assistants (MAs) currently
      play in primary care settings, the paper aims to focus on the work scope and
      dynamics of these increasingly common healthcare personnel.
      DESIGN/METHODOLOGY/APPROACH: This is a multiple step, mixed methods study,
      combining a quantitative survey and qualitative semi-structured interviews: eight
      experts in the field of medical assisting; 12 MAs from diverse primary care
      practice settings in Northern California. FINDINGS: Survey results revealed great
      variation in the breadth of tasks that MAs performed. Five overarching themes
      describe the experience of medical assistants in primary care settings: ensuring
      patient flow and acting as a patient liaison, "making a difference"; diversity
      within the occupation and work relationships. RESEARCH IMPLICATIONS/LIMITATIONS:
      As the number of medical assistants working in primary care practices in the
      United States increases, more attention must be paid to how best to deploy this
      allied health workforce. This study suggests that MAs have an expertise in
      maintaining efficient clinic flow and promoting patient satisfaction. Future
      recommendations for changes in MA roles must address the diversity within this
      occupation in terms of workscope and quality assurance as well as MA
      relationships with other members of ambulatory care teams. ORIGINALITY/VALUE:
      This is the first study to explore perspectives of medical assistants in the USA.
      As this is a largely unregulated and understudied field, a qualitative study
      allowed the exploration of major themes in medical assisting and the
      establishment of a framework from which further study can occur.

PMID- 20698405
TI  - Implementing an emergency department patient admission predictive tool: insights
      from practice.
AB  - PURPOSE: This paper aims to show that identification of expectations and software
      functional requirements via consultation with potential users is an integral
      component of the development of an emergency department patient admissions
      prediction tool. DESIGN/METHODOLOGY/APPROACH: Thematic analysis of semi
      structured interviews with 14 key health staff delivered rich data regarding
      existing practice and future needs. Participants included emergency department
      staff, bed managers, nurse unit managers, directors of nursing, and personnel
      from health administration. FINDINGS: Participants contributed contextual
      insights on the current system of admissions, revealing a culture of crisis,
      imbued with misplayed communication. Their expectations and requirements of a
      potential predictive tool provided strategic data that moderated the development
      of the Emergency Department Patient Admissions Prediction Tool, based on their
      insistence that it feature availability, reliability and relevance. In order to
      deliver these stipulations, participants stressed that it should be incorporated,
      validated, defined and timely. RESEARCH LIMITATIONS/IMPLICATIONS: Participants
      were envisaging a concept and use of a tool that was somewhat hypothetical.
      However, further research will evaluate the tool in practice. PRACTICAL
      IMPLICATIONS: Participants' unsolicited recommendations regarding implementation
      will not only inform a subsequent phase of the tool evaluation, but are eminently
      applicable to any process of implementation in a healthcare setting.
      ORIGINALITY/VALUE: The consultative process engaged clinicians and the paper
      delivers an insider view of an overburdened system, rather than an outsider's
      observations.

PMID- 20698406
TI  - 'Shambolic' training leads to reliance on drug companies.

PMID- 20698407
TI  - GP practices must ensure nurses are trained to do spirometry.

PMID- 20698408
TI  - Harm from omitted and delayed drugs.

PMID- 20698409
TI  - Telehealth enhances self care and independence in people with long term
      conditions.
AB  - The increasing prevalence of long term conditions will influence all nurses'
      practice, irrespective of their particular field. NHS Cornwall is taking part in
      a government trial, known as the whole system demonstrator programme, piloting
      telehealth and telecare to manage long term conditions. This article reports the
      initial positive results.

PMID- 20698410
TI  - How telehealth can increase the effectiveness of chronic heart failure
      management.
AB  - Telehealth offers a way of providing tailored care for patients in their own
      homes. This project, based at a GP practice, found that new technology improved
      patient care and medication concordance and reduced use of healthcare services.
      The initiative is being run along similar lines as the Department of Health's
      whole system demonstrator programme, and shows telehealth also works on asmaller
      scale in an individual practice.

PMID- 20698411
TI  - How nurses can implement the high impact actions to improve quality and cost
      effectiveness.
AB  - In November 2009 the NHS Institute for Innovation and Improvement published a
      list of eight high impact actions for nursing and midwifery and stated that, if
      implemented across the NHS, the actions could save over pounds 9 bn a year while
      improving the quality of care. The NHS Institute has now published a selection of
      case studies from different settings demonstrating successful initiatives
      relating to each action and a range of other supporting material. This article,
      the first in a Nursing Times series summarising the main information on how the
      high impact actions can be achieved, sets the context for the initiative.
      Subsequent articles will discuss the individual actions and offer practical
      information on implementation.

PMID- 20698413
TI  - Human patient simulation can aid staff training in non-invasive ventilation.
AB  - Non-invasive ventilation is increasingly used on general wards to manage
      respiratory disease and staffneed training and clinical experience to use this
      technique effectively. This article describes a training course that used human
      patient simulation to improve healthcare professionals' skills and confidence in
      using and adjusting noninvasive ventilation.

PMID- 20698414
TI  - Dementia care 3: evaluating the effects of wellbeing reviews on residents and
      staff.
AB  - BACKGROUND: This third in a three part series on dementia describes a pilot of
      weekly wellbeing reviews to discuss individual residents' needs on a continuing
      care unit. Part 1 focused on communication and part 2 examined different
      approaches to care. Aim To evaluate the effects of wellbeing reviews on residents
      and care staff. METHOD: A pilot cycle of reviews (one review per resident) was
      carried out, and reports and comments from the reviews analysed. RESULTS: Staff
      appreciated being able to reflect on and discuss a single resident in depth.
      CONCLUSION: Wellbeing reviews are a valuable addition to medically based ward
      rounds, with benefits for staff and residents.

PMID- 20698415
TI  - Ward design must not be restricted to single rooms.

PMID- 20698412
TI  - Using non-invasive ventilation on acute wards: how to provide an effective
      service.
AB  - Non-invasive ventilation is increasingly used on acute wards to treat patients
      with acute type 2 hypercapnic respiratory failure. This article highlights the
      main factors that should be considered in providing an acute NIV service outside
      of a critical care setting.

PMID- 20698416
TI  - Nurses aren't sunbathing while HCAs do the work.

PMID- 20698417
TI  - Influence of thermomechanical fatigue loading on the fracture resistance of all
      ceramic posterior crowns.
AB  - This study evaluated the fracture resistance and the survival rate of different
      all-ceramic crowns in-vitro after thermomechanical fatigue loading in comparison
      to porcelain-fused-to-metal posterior crowns. Sixteen crowns for human mandibular
      first molars were made of each of the following: Cercon, IPS-Empress 2 In-Ceram
      Zirconia, Procera AllZircon and porcelain-fused-to-metal. Half of the specimens
      of each group was thermocycled and dynamically loaded using a chewing simulator
      All samples were thereafter tested for the maximum fracture resistance. The
      survival rates after 1-2 million cycles in the artificial mouth were 100% in all
      the tested crown systems. The chewing simulation and thermocycling did not
      significantly decrease the fracture strength of the ceramic crowns (P>0.005). The
      median fracture load of Cercon, Procera AllZircon, In-Ceram Zirconia and PFM was
      significantly higher than IPS-Empress 2 both for loaded and non loaded groups
      (P<0.005) while the difference between Cercon, Procera AllZircon, In-Ceram
      Zirconia and PFM was not significant (P>0.005). All-ceramic systems showed
      fracture load values similar to those of porcelain-fused-to-metal molar crowns
      and therefore may be considered for use in clinical studies.

PMID- 20698418
TI  - Fabrication of a fixed provisional implant restoration. A report of three cases.
AB  - A clinical problem for patients with posterior partial edentulism who are going
      to be treated with dental implants is provisionalization during the period of
      soft and hard tissues preparation, the period of osseointegration and
      construction of the final restoration. Up to now, the available solutions were
      either the construction of a removable prosthesis or immediate loading of
      implants. The purpose of this article is to present an alternative technique for
      fabricating a fixed provisional restoration in patients with posterior partial
      edentulism. It is referred to as a teeth-tissue supported restoration which
      retention and support is provided from prepared or unprepared teeth while support
      also is gained from the maxillary tubercles or the retromolar pads of the upper
      and lower jaws.

PMID- 20698419
TI  - Tensile strength of laser welded cobalt-chromium alloy with and without an argon
      atmosphere.
AB  - The tensile strength and depth of weld of two cobalt chromium alloys before and
      after laser welding with and without an argon gas atmosphere were investigated.
      Using two cobalt chromium alloys, rod shaped specimens (5 cm x 1.5 mm) were cast.
      Specimens were sand blasted, sectioned and welded with a pulsed Nd: YAG laser
      welding machine and tested in tension using an Instron universal testing machine.
      A statistically significant difference in tensile strength was observed between
      the two alloys. The tensile strength of specimens following laser welding was
      significantly less than the unwelded controls. Scanning electron microscopy
      showed that the micro-structure of the cast alloy was altered in the region of
      the weld. No statistically significant difference was found between specimens
      welded with or without an argon atmosphere.

PMID- 20698420
TI  - The heat emitted from some QTH and LED light curing units in consecutive
      activations. A laboratory assessment.
AB  - The temperature rises produced by two Quartz-Tungsten-Halogen (QTH) bulb and four
      solid-state light emitting diode (LED) light curing units (LCU's) was measured on
      five separate occasions following (i) activation for 40 seconds and (ii) three
      consecutive activations of 40 seconds. For both periods of activation evaluated
      the Luxor QTH LCU exhibited significantly (P<0.01) lower temperature rises (1.2
      (0.2) - 2.5 (0.4) degrees C) than all other LCU's. In the case of the consecutive
      applications the temperature rises, for the other units, exceeded known threshold
      temperaturesforpulpitis to be risked.

PMID- 20698421
TI  - Marginal behaviour of self-etch adhesive/composite and combined amalgam-composite
      restorations.
AB  - The aim of this study was to compare the marginal and internal adaptation in self
      etching adhesive (SEA)/composite restorations with combined amalgam-resin-based
      composite restorations in the proximal box with and without bonding agent beneath
      amalgam both before and after load-cycling. Class II restorations, were
      manufactured as following a) Bonding agent (Clearfil Liner Bond 2V, Kuraray)
      beneath amalgam (Tytin, SDS Kerr) and resin-based composite (Clearfil APX,
      Kuraray) with SEA, b) Amalgam without bonding agent and resin-based composite
      with SEA and c) Resin-based composite with SEA. Each group divided into two equal
      subgroups (n=8). Marginal and internal adaptation of first subgroup evaluated
      after 7-day water storage and of the second after load-cycling in chewing
      simulator for 1.2 x 10(6) cycles. Marginal and internal adaptation at cervical
      and amalgam-composite sites evaluated by videomicroscope and ranked as
      "excellent"/"non-excellent". Slices of restorations examined under optical
      microscope to determine the quality of bonding layer. Defects in cervical
      adaptation observed in the three restorative techniques examined prior loading.
      Amalgam-composite combination in proximal surface provided comparable marginal
      and internal adaptation results at cervical wall, to self-etching-composite
      combination. Portion (25-37.5%) of amalgam-resin-based composite interfaces in
      proximal box presented no perfect sealing. The application of bonding agent
      beneath amalgam resulted in relatively inferior cervical adaptation. Loading
      resulted in fewer excellent restorations in all three restorative techniques but
      not in a statistically significant level.

PMID- 20698422
TI  - Three-dimensional positional changes of teeth adjacent to posterior edentulous
      spaces in relation to age at time of tooth loss and elapsed time.
AB  - The purpose of this study was to study the stability of teeth adjacent to
      posterior edentulous spaces and correlate it with patient age and time lapse
      since tooth loss. Dental casts, panoramic radiographs, and questionnaires of
      patients treated in a University setting were employed. Teeth adjacent and
      opposing posterior edentulous spaces were examined for the following parameters:
      Supraeruption, rotation, space closure, and axial inclination. One hundred twenty
      three patients with 229 edentulous spaces were analyzed. Statistical analysis
      showed that the effects of "jaw", "gender", and "age group at the time of tooth
      loss" were not significant for any of the variables tested. The effect of time
      lapse since tooth loss was significant regarding the "amount of distal tooth
      inclination" (P<0.001), the "amount of distal tooth rotation" (P=0.004), and
      "space closure" (P=0.038). Post-hoc analysis of the "amount of distal tooth
      inclination" revealed a marked increase in inclination 5 years after tooth loss.
      Within the limitations of this study, it was concluded that in the group of
      patients studied, minor positional changes in teeth opposing or adjacent to
      posterior edentulous spaces had occurred. The greatest changes in position were
      recorded for mandibular teeth distal to edentulous spaces.

PMID- 20698423
TI  - Temperature rise during intraoral polymerization of self-cured hard denture base
      liners.
AB  - The aim of this in-vivo study was to evaluate the temperature rise during
      polymerization of five chairside self-cured hard denture base reliners. For the
      same patient, 30 identical baseplates, exposing a space on their tissue surface
      to accommodate the lining material, were made of a light-cured denture base
      material. A hole was drilled in the center of this area to enable the
      thermocouple wire of the temperature measuring device to have direct access to
      the palatal surface of the baseplate. Six baseplates were used for each of the
      five lining materials tested. Temperature recordings were made every 15 seconds.
      Data were analyzed using single factor analysis of variance (ANOVA) and the
      Scheffe's post-hoc analysis for multiple comparisons. The mean maximum
      temperature values ranged from 40.2 degrees C to 45.7 degrees C being
      statistically different among the materials (P<0.001). The maximum peak
      temperature was 53 degrees C and the lowest 39 degrees C. Also the difference
      between the time each material reached the peak of temperature was statistically
      significant (P<0.0001). A temperature range of 5.5 degrees C was demonstrated
      among materials, with the highest polymerization temperatures recorded for
      Flexacryl Hard and the lowest for Rebase and GC Reline hard. Ufi-gel hard showed
      the fastest polymerization cycle and was the first to reach the maximum
      temperature. The available chairside hard liners must be chosen with care
      considering the thermal effect on the oral mucosa and the discomfort of patient.

PMID- 20698424
TI  - Colour stability, opacity and cross-link density of composites submitted to
      accelerated artificial aging.
AB  - The study evaluated the influence of accelerated artificial aging on colour
      stability, opacity and cross-link density of resin-based composites (RBCs). Seven
      specimens were obtained of five RBCs (Heliomolar, 4 Seasons, Tetric Evo Ceram, SR
      Adoro), which were submitted to colour stability and opacity analysis and cross
      link density evaluation. All tests were performed before and after aging. After
      statistical analysis (one-way ANOVA; Tukey; p<0.05), it was observed that QuiXfil
      and SR Adoro presented colour alteration values above those that are clinically
      acceptable (deltaE=5.77 and 4.34 respectively) and the variation in opacity was
      lowest for SR Adoro. There was an increase in the cross-link density of all
      studied materials after aging.

PMID- 20698425
TI  - A multidisciplinary methodology for the evaluation of products that assist with
      bed mobility.
AB  - This article presents a multidisciplinary approach to evaluating products that
      assist with bed mobility. Following multidisciplinary risk assessments on 10
      mattress elevators, 24 participants tested four different products for periods of
      up to 1 week. The participants, recruited by health professionals, were asked to
      test four different mattress elevators and, if possible, test each allocated
      product for a week at a time in their own home. The Barthel Activities of Daily
      Living Index, a sitting balance assessment using a subscale of the motor
      assessment scale, and the Waterlow score were used to aid comparison of the
      products and their performance in practice. All products assisted with bed
      mobility, particularly lying-to-sitting and giving support in sitting. Technical
      and manual handling risk assessments were undertaken by a panel of experts in a
      laboratory on the products using a predetermined checklist. Guidelines for
      choosing these products were compiled from the results of both the risk
      assessments and the user evaluations.

PMID- 20698426
TI  - Effects of audio feedback on sitting behaviors of community-dwelling manual
      wheelchair users with spinal cord injuries.
AB  - The purpose of this study was to investigate whether audio feedback obtained from
      a data logger could help community-dwelling manual wheelchair users (MWUs) to
      engage in pressure-relieving behaviors more frequently. Twenty community-dwelling
      MWUs completed the study. Data loggers with force sensors were installed on each
      participant's wheelchair. The frequency of pressure-relief activities and sitting
      time were recorded on two occasions one week apart with or without audio
      feedback. The results showed that MWUs spent approximately 9.2 hours per day
      sitting in their wheelchairs and performed an average of 5.1 transfers from their
      wheelchair. MWUs receiving audio feedback showed a significant increase in
      pressure-relieving activities, which included push-up frequency and side-to-side
      lean frequency with less uninterrupted sitting time. Although the audio alarm
      device served as a useful tool in promoting pressure-relieving behaviors, our
      subject population still showed low frequency of pressure-relief activities. This
      might indicate that other factors besides pressure may explain why our subjects
      are free from pressure ulcers. Educational materials should include not only
      information related to pressure but to other risk factors believed to contribute
      to the development of pressure sores.

PMID- 20698427
TI  - Perceptions of writing and communication aid use among children with a physical
      disability.
AB  - Children with physical disabilities (CPD) often experience decreased
      opportunities to participate in daily occupations. Occupational therapists (OTs)
      prescribe writing and communication aids; however, little is known about this
      population's perceptions of the technology. This qualitative study explored the
      perceptions that CPD had regarding their writing and communication aids. Children
      were interviewed; a focus group of one parent and two OTs provided context to the
      children's comments. Enablers and barriers to using communication aids were
      found. Participants reported a greater sense of pride, more self-confidence, and
      a greater sense of autonomy and productivity with the technology. Analysis of the
      interviews, focus group, and reflective notes resulted in a model showing how
      enablers and barriers of on-screen technology usage relates to occupational
      enhancement or occupational detriment. This study contributes to an understanding
      of the meaning that CPD associate with writing technology and the factors
      associated with usage.

PMID- 20698428
TI  - Difficulties in automatic speech recognition of dysarthric speakers and
      implications for speech-based applications used by the elderly: a literature
      review.
AB  - Despite their growing presence in home computer applications and various
      telephony services, commercial automatic speech recognition technologies are
      still not easily employed by everyone; especially individuals with speech
      disorders. In addition, relatively little research has been conducted on
      automatic speech recognition performance with older adults, in whom speech
      disorders are commonly present. As one ages, the older adult voice naturally
      begins to resemble some aspects of mildly dysarthric speech. Dysarthria, a common
      neuromotor speech disorder, is particularly useful for exploring performance
      limitations of automatic speech recognizers owing to its wide range of speech
      expression. This article reviews clinical research literature examining the use
      of commercial speech-to-text automatic speech recognition technology by
      individuals with dysarthria. The main factors limiting automatic speech
      recognition performance with dysarthric speakers are highlighted and extended to
      the elderly using a specific example of a novel, automated, speech-based personal
      emergency response system for older adults.

PMID- 20698429
TI  - Optimizing the usability of mobile phones for individuals who are deaf.
AB  - Mobile phones are employed as an assistive platform to improve the living quality
      of individuals who are deaf. However, deaf individuals experience difficulties
      using existing functions on mobile phones. This study identifies the functions
      that are inadequate and insufficient for deaf individuals using existing mobile
      phones. Analytical results were referenced by designers to optimize mobile phone
      functions for the deaf community. A simulated mobile phone interface, the
      PeacePHONE, was designed to evaluate functions. Functions were developed based on
      the conceptual design of a multifunction mobile phone. This conceptual design was
      based on the daily life requirements of individuals who are deaf. PeacePHONE
      usability was tested by 18 deaf individuals. Five factors were assessed: user
      experience profile, user perceived usability, functions on existing mobile phones
      that should be retained, new functions that should be added to existing mobile
      phones, and functions that are most useful to individuals who are deaf. Positive
      and negative feedback on the PeacePHONE is presented as well.

PMID- 20698430
TI  - Imperative that Tennessee dentists join the Controlled Substance Monitoring
      Database.

PMID- 20698431
TI  - Controlled Substance Monitoring Database (CSMD).

PMID- 20698432
TI  - The oral biopsy: indications, techniques and special considerations.

PMID- 20698433
TI  - Effects of an oral health education program for pregnant women.
AB  - PURPOSE: The purpose of this study was to evaluate the gain in knowledge of oral
      health after education to pregnant women on dental anticipatory guidance and to
      determine how much of this information pregnant women retain over time. METHODS:
      The study consisted of 40 pregnant women. Inclusion criteria included: (1)
      between the ages of 21-40; (2) in 12-40th week of pregnancy; and (3) spoke
      English. During the first visit, all subjects were asked to complete a pre-test
      (24 questions), watch a ten minute presentation and complete the post-test (24
      questions). During the second visit (4 weeks/1 month after the first visit), all
      subjects were asked to complete the follow-up test (24 questions). RESULTS: All
      of the tests (pre, post and follow-up) were scored and used to determine the
      changes in knowledge of the pregnant women after the presentation. The mean age
      for all 40 pregnant women was 26.88 (SD +/- 4.3) years and the mean number of
      weeks pregnant was 25.2 at the first visit. The mean overall correct scores for
      the pre-test was 12.9 (53.75%), post-test was 20.9 (87.08%) and follow-up test
      was 20.17 (84.05%). These overall scores show an improvement of 8 (33.33%,
      p<0.05) questions correct from the first to second test, and a digression of 0.73
      (3.08%) questions correct from the second to third test. CONCLUSIONS: These
      observations indicate that in this study population pregnant women's knowledge
      improved after a presentation on dental anticipatory guidance. These observations
      also indicate that after four weeks, pregnant women were able to retain most of
      the information, as only a slight digression in overall scores was noticed from
      the follow-up test to the post-test.

PMID- 20698434
TI  - Developing a fixture level cast for implants with interfering axial convergence.
AB  - This article presents a novel technique for developing a master cast for two
      implants which are clinically placed convergent and very close to each other. The
      technique consists of making an implant level impression using a transfer coping
      for the posterior implant. Then fabricate a positional index intraorally, which
      contains a registration of the second transfer coping, the healing abutment
      reattached from the transfer in the impression and the adjacent teeth. The master
      cast is altered, using this positional index to incorporate the second implant
      analog.

PMID- 20698435
TI  - Quick and easy: Indirect fabrication of composite veneers.
AB  - Composite veneers can be fabricated directly on a vinyl polysiloxane (VPS) die.
      Using the following technique, a dentist (or their trained auxiliary) can quickly
      fabricate an esthetic composite veneer with an acceptable marginal fit. This
      article describes such a technique.

PMID- 20698436
TI  - Seroprevalence of Cryptosporidium parvum infection of dairy cows in three
      northern provinces of Thailand determined by enzyme-linked immunosorbent assay
      using recombinant antigen CpP23.
AB  - Cryptosporidium parvum is the most frequent parasitic agent that causes diarrhoea
      in AIDS patients in Thailand. Cryptosporidiosis outbreaks in humans may be
      attributed to contamination of their drinking water from infected dairy pastures.
      A 23-kDa glycoprotein of C. parvum (CpP23) is a sporozoite surface protein that
      is geographically conserved among C. parvum isolates. This glycoprotein is a
      potentially useful candidate antigen for the diagnosis of cryptosporidiosis by
      enzyme-linked immunosorbent assay. Therefore, we investigated the seroprevalence
      of C. parvum infection in dairy cows in northern Thailand using an ELISA based on
      recombinant CpP23 antigen. Sera were randomly collected from 642 dairy cows of 42
      small-holder farmers, which had the top three highest number of the dairy cows'
      population in Northern Thailand, that included Chiang Mai, Chiang Rai and Lumpang
      provinces. The overall seroprevalence of the infection was 4.4%, and the
      seropositive rates for the three provinces were 3.3% in Chiang Mai, 5.1% in
      Chiang Rai and 3% in Lumpang. These results suggest that cattle could play a role
      in zoonotic cryptosporidiosis in Thailand.

PMID- 20698437
TI  - Ticks collected from birds in the northern provinces of South Africa, 2004-2006.
AB  - Approximately 3000 birds, mainly passerines, caught in mist nets in the northern
      provinces of South Africa, were examined for ticks. A total of 178 ticks,
      belonging to 14 species, were recovered from 83 birds of 43 different species.
      Hyalomma rufipes was the most numerous tick, with 26 larvae and 109 nymphs
      collected, followed by Amblyomma marmoreum, with 13 larvae and two nymphs.
      Despite the study being conducted within the distribution range of Amblyomma
      hebraeum, it was not seen on any passerines, whereas three larger species were
      infested. The potential for small birds to spread ticks with their associated
      tick-borne pathogens is discussed.

PMID- 20698438
TI  - Ticks (Acari: Ixodidae) infesting camels (Camelus dromedarius) in Northern Sudan.
AB  - Monthly total body tick collections from 13-20 camels were conducted for 2
      consecutive years (2000-2001) in Northern Sudan. Tick populations were correlated
      with locality, season, predeliction site, sex and coat colour. Hyalomma
      dromedarii was found to be the predominant (89%) tick species infesting the
      camels. Other tick species found in very low numbers were Hyalomma impeltatum
      (7.7%), Hyalomma anatolicum anatolicum (3.3%), Hyalomma truncatum (0.29%),
      Hyalomma marginatum rufipes (0.25%), Rhipicephalus praetextatus (0.30%) and
      Rhipicephalus sanguineus group (0.09%). Nymphs of the genus Hyalomma were
      collected in significant numbers. Adult ticks significantly preferred to attach
      to the lower parts of the camel's body for feeding while the nymphs preferred the
      back of the animal. Female camels harboured more ticks than males while higher
      infestations were recorded on camels with a grey coat colour compared to those
      with a brown coat colour. Ticks were found on camels throughout the year and
      increased in numbers during March to October with a peak in September.

PMID- 20698439
TI  - Report on some monogenean and clinostomid infestations of freshwater fish and
      waterbird hosts in Middle Letaba Dam, Limpopo Province, South Africa.
AB  - This report deals with the results of a parasitological study done as part of a
      post-impoundment ecological study of Middle Letaba Dam, Limpopo Province, South
      Africa. It involved a seasonal survey protocol with particular attention to the
      diversity and prevalence of the parasitic fauna of the indigenous fish community
      of the dam and the role of selected fish-eating birds in the life cycle and
      distribution of fish helminths. The potential species composition of fish of the
      dam is provided. Monogenean and clinostomatid parasites encountered are listed
      and infestation statistics of fish and fish-eating bird hosts are presented. The
      results of this study also provide information on new distribution and host
      records of the encountered monogeneans.

PMID- 20698440
TI  - The comparative prevalence of five ixodid tick species infesting cattle and goats
      in Maputo Province, Mozambique.
AB  - This study compares the prevalence of ixodid tick species on cattle and goats in
      Maputo Province. Adult ticks as well as the nymphs of three species, and only the
      adults of two species were collected from sets of five cattle at 21 localities
      throughout the province and compared with those collected from similar sets of
      goats at the same places. Amblyomma hebraeum adults and/or nymphs were present on
      cattle and on goats at all 21 localities, and 90 cattle and 22 goats were
      infested with adult ticks. Rhipicephalus (Boophilus) microplus adults and/or
      nymphs were collected from cattle at 20 and from goats at 15 localities, and 92
      cattle and 34 goats were infested [Chi-square test (chi2), P<0.001]. The total
      length of several maturing female R. (Boophilus) microplus collected from cattle
      and goats exceeded 5 mm, indicating that they successfully engorge on both host
      species. Rhipicephalus appendiculatus adults and/or nymphs were present on cattle
      at 15 and on goats at 13 localities, but 28 cattle and only one goat were
      infested with adult ticks (chi2, P<0.001). Adult Rhipicephalus evertsi evertsi
      were recovered from cattle at 20 and from goats at 17 localities, and 74 cattle
      and 69 goats were infested. Adult Rhipicephalus simus were collected from cattle
      at 18 and from goats at 11 localities (Fisher's exact test, P=0.04), and 60
      cattle and 14 goats were infested (chi2, P<0.001). These findings underscore the
      advisability of including goats in acaricide application programmes designed for
      the control of tick-borne diseases in cattle at the same locality.

PMID- 20698441
TI  - Molasses as a possible cause of an "endocrine disruptive syndrome" in calves.
AB  - During the mid 1990s a potentially serious, chronic syndrome was reported in well
      managed beef and dairy herds from unrelated parts of South Africa. Farmers
      reported that it manifested as various combinations of decreased production,
      decreased weaning masses, apparent immune breakdown in previously immunocompetent
      animals, increased reproductive disorders, various mineral imbalances in non
      deficient areas and goitre, noticeable as enlarged thyroid glands. The farmers
      associated this syndrome with certain batches of sugar cane molasses and molasses
      based products. The syndrome was reminiscent of an "endocrine disruptive
      syndrome". The objective of this study was to evaluate the suspected endocrine
      disruptive effect of molasses included in cattle feed. Using existing in vitro
      assays, four batches of molasses syrup were screened for possible inclusion in a
      calf feeding trial. Two batches were selected for the trial. Thirty-two, 4- to 6
      week-old, weaned Holstein bull calves were included in the single phase, three
      treatment, parallel design experiment. In two of the groups of calves, two
      different batches of molasses were included in their rations respectively. The
      control group was fed a ration to which no molasses was added, but which was
      balanced for energy and mineral content. The mass gain of the calves was recorded
      over the 6-month study period. The calves were clinically examined every week and
      clinical pathology parameters, immune responses and endocrine effects were
      regularly evaluated. Even though endocrine disrupting effects were detected with
      the in vitro screening assays, these could not be reproduced in the calves in the
      experiment. The two batches of molasses utilized in the calf feeding trial did
      not induce major differences in any of the parameters measured, with the
      exception of a lower mass gain in one of the molasses-fed groups (Group 1), which
      tended towards significance. The results of the study indicate that the two
      batches of molasses had no endocrine disruptive or immunosuppressive effects in
      calves.

PMID- 20698442
TI  - Ecological parameters of Lamproglena hoi (Copepoda: Lernaeidae) infection on the
      Bushveld smallscale yellowfish, Labeobarbus polylepis (Boulenger, 1907).
AB  - This study describes the distribution and aspects of the ecology of Lamproglena
      hoi. Bushveld small-scale yellowfish, Labeobarbus polylepis (Boulenger, 1907)
      were collected during June 2006 from the Phongolo and Assegaai rivers, March 2005
      and October 2006 from the Elands River, and January 2007 and June 2008 from the
      Komati River in Mpumalanga, South Africa and examined for the presence of
      parasites. Lamproglena hoi specimens were collected from the gill filaments of
      the host. Specimens were fixed with warm AFA (alcohol-formaldehyde-acetic acid)
      and preserved in 70% ethanol. The identification of parasites took place in the
      laboratories of the University of Johannesburg. Twenty-five copepods (prevalence
      21%, mean intensity = 4.17, abundance = 0.86) were collected on 29 fish in the
      Phongolo River and 46 copepods (prevalence 40%, mean intensity = 3.83, abundance
      = 1.53) were collected on 30 fish in the Assegaai River. One hundred and sixty
      eight copepods (prevalence 52%, mean intensity = 12.92, abundance = 6.72) were
      collected on 25 fish in 2005, and 527 copepods (prevalence 95%, mean intensity =
      27.74, abundance = 26.35) were collected on 20 fish in the Elands River. One
      hundred and sixteen copepods (prevalence 75%, mean intensity = 7.73, abundance =
      5.80) were collected on 20 fish in 2007, and 273 copepods (prevalence 63%, mean
      intensity = 16.06, abundance = 10.11) were collected on 27 fish in 2008 in the
      Komati River. Labeobarbus polylepis from these four rivers was found to have a
      relatively high L. hoi infection. Inseminated L. hoi females (immature) attach to
      the host in winter and their ovaries become conspicuous (mature). In spring
      fertilized eggs are stored in egg sacs hanging from the body (gravid), indicating
      that fertilized eggs start to hatch in spring and continued hatching into summer.
      Parasites prefer the median part of the second gill arch for attachment. No
      correlation exists between the number of parasites recorded on the gills and the
      sizes (total lengths) of yellowfish sampled.

PMID- 20698443
TI  - Tick infestation, and udder and teat damage in selected cattle herds of
      Matabeleland South, Zimbabwe.
AB  - A cross-sectional survey was conducted to determine tick infestation, and udder
      and teat damage in 286 lactating cows and heifers at six properties in the
      smallholder and commercial sectors in Gwanda district of Matabeleland South
      Province, Zimbabwe. Eight tick species were identified: Amblyomma hebraeum,
      Hyalomma truncatum, Hyalomma marginatum rufipes, Rhipicephalus evertsi evertsi,
      Rhipicephalus (Boophilus) decoloratus, Rhipicephalus appendiculatus,
      Rhipicephalus zambeziensis and Rhipicephalus simus. Overall, 81.5% of the cattle
      were tick infested; prevalence of tick-infested cattle was significantly higher
      on communal land (93.8%) and recently claimed land (85.1%) than on commercial
      farms. The mean tick load on infested cattle on communal land was significantly
      higher than in the other two sectors. Although 53% of the sampled cattle had some
      degree of udder and teat damage, very few farmers (2.6%) treated their cattle for
      these conditions. Udder damage was ca. two times and three times, respectively,
      more likely to occur in cattle on communal land compared to cattle on recently
      claimed land and commercial farms. The occurrence of R. appendiculatus and R.
      zambeziensis indicate that the cattle population in the study area is at high
      risk of a theileriosis outbreak, a tick-borne disease that has not been reported
      from this area.

PMID- 20698444
TI  - Curtisia dentata (Cornaceae) leaf extracts and isolated compounds inhibit
      motility of parasitic and free-living nematodes.
AB  - Haemonchus contortus and Trichostrongylus colubriformis are among the most
      important parasitic nematodes of small ruminants. Caenorhabditis elegans, a free
      living nematode, is used as a model for evaluating anthelmintic activity of a
      variety of test substances. Extracts of several medicinal plants are useful in
      vitro and in vivo against nematode development. Extracts of Curtisia dentata, a
      South African medicinal plant, and compounds isolated from leaves of this plant
      were investigated for anthelmintic activity against T. colubriformis, H.
      contortus and C. elegans. The acetone and dichloromethane extracts were active
      against all nematodes at concentrations as low as 160 microg/ml. Betulinic acid
      and lupeol were active against the parasitic nematodes only at the high
      concentrations of 1000 and 200 microg/ml, respectively. All compounds were
      effective against C. elegans with active concentrations as low as 8 microg/ml.
      Betulinic acid was less active than lupeol and ursolic acid against C. elegans.
      The acetone and dichloromethane extracts were also active against C. elegans with
      a concentration of 0.31 mg/ml resulting in almost 80% inhibition of larval
      motility. The use of free-living nematodes may provide information on the
      activity of potential anthelmintics against parasitic nematodes. Extracts of
      various medicinal plant species may provide solutions to ill-health of small
      ruminants caused by parasitic nematodes in poor communities of southern Africa.

PMID- 20698445
TI  - Evaluation of a rapid immunodiagnostic test kit for detection of African
      lyssaviruses from brain material.
AB  - A rapid immunodiagnostic test kit was evaluated against a selection of isolates
      of lyssavirus genotypes occurring in Africa. The test was carried out in parallel
      comparison with the fluorescent antibody test (FAT) and isolates representing
      previously established phylogenetic groups from each genotype were included. The
      specificity of the rapid immunodiagnostic test compared favourably with the FAT
      and was found to detect all representatives of genotypes 1, 2, 3 and 4 in brain
      samples of either field cases or suckling mouse brain inoculates.

PMID- 20698446
TI  - Rheumatoid forefoot reconstruction.
AB  - Management of the patient with rheumatoid forefoot deformity requires a
      multidisciplinary integrated approach for a successful outcome. Despite recent
      advances in the pharmacological management of rheumatoid arthritis and its impact
      upon disease progression, forefoot deformity and pain remain common
      manifestations requiring input from orthopaedic surgeons. The typical deformities
      encountered include hallux valgus, with subluxation or frank dislocation at the
      lesser metatarsophalangeal (MTP) joints. Surgical intervention is directed at
      correcting and decompressing these deformities, with the ultimate goal of a
      stable, painless, functional plantigrade foot. Although a variety of surgical
      options exist, fusion of the 1st MTP joint with lesser MTP joint excision
      arthroplasty remains the gold standard, upon which newer procedures should be
      judged. This article reviews the pathophysiology of forefoot deformity in
      rheumatoid arthritis with special emphasis on recent advances in surgical
      management.

PMID- 20698447
TI  - Wound closure in flexion versus extension following total knee arthroplasty: a
      systematic review.
AB  - Optimising knee range of motion following total knee arthroplasty (TKA) is
      important for patient satisfaction, functional outcome and early rehabilitation
      to promote accelerated discharge. Historically, wound closure following TKA has
      been performed in extension. It has been suggested that knee position during
      wound closure may influence range of motion and clinical outcomes following TKA.
      The purpose of this study was to determine whether TKA wounds should be closed in
      flexion or extension. An electronic search of MEDLINE, EMBASE, CINAHL and AMED
      databases was made in addition to a review of unpublished material. All included
      papers were critically appraised using a modified PEDro (Physiotherapy Evidence
      Database) critical appraisal tool. Three papers were eligible, assessing 237
      TKAs. On analysis, patients with TKA wounds closed in flexion had greater flexion
      range of motion and required less domiciliary physiotherapy compared to those
      with wounds closed in full extension. The specific degree of knee flexion used
      when closing total knee replacement wounds may be an important variable to
      clinical outcome. However, the present evidence-base is limited in both size and
      methodological quality.

PMID- 20698448
TI  - Acromioclavicular joint reconstruction using anchor sutures: surgical technique
      and preliminary results.
AB  - A number of surgical procedures have been described for reconstruction of the
      disrupted acromioclavicular (AC) joint. Among these is the use of anchor sutures
      tied over a small button plate. The present study aims to evaluate the
      preliminary results with this technique in 15 patients with a mean age of 31
      years (range: 19-48 years). The shoulder was evaluated clinically using the
      Constant-Murley Shoulder Score, and radiologically. Indication for surgery was
      Rockwood type IV-V AC joint dislocation. All patients returned to work within a
      mean time of 11.2 weeks (range 8-18) postoperatively. The mean Constant-Murley
      Shoulder Score at last follow-up was 92.8. Postoperative radiographs confirmed
      anatomic reduction in all patients. Residual subluxation occurred in one patient
      and dislocation occurred in another. All patients except one were satisfied with
      the results in terms of functional performance and cosmetic appearance. In
      conclusion, considering its low morbidity, unnecessary hardware removal and
      minimal complications from breakage or migration of metal implants, this
      technique appears to offer a good alternative in AC joint stabilization.

PMID- 20698449
TI  - Missed elbow fractures misdiagnosed as radial head subluxations.
AB  - Over a 36-month period, 11 children were treated in our department for fractures
      about the elbow which initially went undiagnosed, as they had first undergone
      reduction maneuvers for a suspected radial head subluxation, without prior
      imaging. The most frequent final diagnosis was supracondylar humerus fracture (n
      = 4). A fall was reported for six children (54.5%); the mechanism of injury
      remained unknown in four children (36.4%). In four of eleven children (36.4%)
      there was moderate or major soft tissue swelling at the time of first
      presentation, which is uncommon in radial head subluxation. Reduction of a
      suspected radial head subluxation without any prior radiological investigation
      can be recommended exclusively when the typical history of an abrupt traction by
      an (adult) attending person is positively reported. In every other case,
      radiographs should be done prior to any attempt at reduction.

PMID- 20698450
TI  - A high prevalence of Dupuytren's disease in Flanders.
AB  - Dupuytren's disease has been the subject of numerous epidemiological surveys
      attempting to expand our knowledge on its origin and spread. In Flanders,
      although numerous studies on surgical outcome have been reported, information on
      prevalence of Dupuytren's disease is lacking. Therefore, Flanders' population in
      a non-hospital environment was studied by a clinical evaluation performed by a
      single hand specialist. Five different market places spread geographically in the
      5 Flemish provinces of Belgium were visited to examine the hands of randomly
      chosen individuals over 50 years old visiting the market. In all, 500 people were
      examined; Dupuytren's disease was found to be present in 32% of the population.
      Nodules without finger contractures (stage 1) were seen in 24% of the population,
      in comparable proportions in males (28%) and females (20%). However, finger
      contractures (stage 2) were seen in 8%, significantly more often in males (11%)
      than in females (4%). The prevalence of stage 1 is somewhat lower in individuals
      over 80 years old. In men, the incidence of stage 2 was found to increase with
      age. These findings were compared with literature data on the prevalence of
      Dupuytren's disease in other countries and populations. It appears that, similar
      to northern Europe, Dupuytren's disease is also a common disease in Flanders.

PMID- 20698451
TI  - Entrapment of the proximal sciatic nerve by the hamstring tendons.
AB  - The purpose of this study was to evaluate the results of operative treatment of
      entrapment of the sciatic nerve by tight fibrous structures associated with the
      hamstring tendons close to their proximal insertion. We retrospectively evaluated
      the results of 22 operations performed in 16 patients (6 bilateral operations),
      on average six years postoperatively. There was complete relief in 11 cases, good
      relief in 8 cases and fair relief in 3 cases. Entrapment of the proximal sciatic
      nerve by the hamstring tendons is not presented in standard textbooks. However,
      this condition is not extremely rare. A wide range of material has been published
      on operative treatment of the hamstring syndrome, but the patients were
      essentially active athletes. Our material consisted of ordinary patients who were
      referred to the university central hospital for orthopaedic consultation. The
      results of surgical treatment of hamstring syndrome are very encouraging.

PMID- 20698452
TI  - Acetabular labral tears following pregnancy.
AB  - Acetabular labral tears are usually seen in individuals in whom the hip is
      exposed to elevated axial and torsional forces. In our experience we have
      encountered a series of female patients in whom symptom onset was during
      pregnancy or obstetric labour. We reviewed our patient database to identify all
      patients who had undergone hip arthroscopy in our hospital. The records of female
      patients who had a labral tear on arthroscopy and in whom symptom onset was
      clearly documented to be during pregnancy or labour were identified. We report
      three cases of acetabular labral tear occurring during pregnancy or labour. This
      represents 7% of all female patients undergoing hip arthroscopy during a two-year
      period. Ligamentous laxity and altered cartilage matrix during pregnancy may
      predispose to acetabular labral injury. Clinicians need to be aware of this
      possible intra-articular lesion in peripartum patients presenting with hip or
      buttock pain, and manage appropriately.

PMID- 20698453
TI  - Arthrodiastasis and surgical containment in severe late-onset Perthes disease: an
      analysis of 14 patients.
AB  - Late-onset Perthes disease usually carries a poor prognosis. In severe cases
      there may be increasing pain, decreased range of motion and hinge abduction which
      forms a contraindication for surgical containment. We have managed 14 such
      patients in a two-stage procedure. Arthrodiastasis done as a first stage
      dramatically reduced pain and Trendelenburg limp while at the same time leading
      to a substantial improvement in range of motion and hinged abduction. Once the
      contraindications to surgical containment were overcome by arthrodiastasis, we
      proceeded with a varus osteotomy of the femur in a second stage in the hope that
      the femoral head would remodel to some extent with time and would improve the
      final functional outcome.

PMID- 20698454
TI  - Bone mineral density in young Indian adults with traumatic proximal femoral
      fractures. A case control study.
AB  - There is scarcity of data on osteoporosis in India for the age group of 20-40
      years when peak bone mass is achieved. This study aimed to assess bone mineral
      density (BMD) in patients in this age group with traumatic proximal femoral
      fractures, and to compare it with age matched controls. Thirty patients aged 20
      to 40 years with traumatic proximal femoral fractures and 30 healthy volunteers
      within the same age group were included in the study. Radiographs of the pelvis
      were taken to determine the Singh index, and DEXA scan of the unaffected hip was
      done to assess BMD. Fracture cases were compared with controls for significant
      difference in BMD. The male to female ratio of the study was 2:1. Based on
      Singh's index, 60% of fracture cases and 20% of controls were osteoporotic. T
      scores by DEXA revealed that 24 patients with fracture and 22 controls had
      osteopenia or osteoporosis. There was a significant difference in the Singh index
      between the two groups and no significant difference in BMD assessed by DEXA
      scan. No agreement was found between BMD determined by DEXA and Singh's index.
      The study points that our population fails to attain an adequate peak bone mass.
      It also questions the applicability of Western data to Indian population. The
      findings also indicate that Singh's Index cannot substitute DEXA for diagnosis of
      osteoporosis.

PMID- 20698455
TI  - Misdiagnosis of occult hip fracture is more likely in patients with poor mobility
      and cognitive impairment.
AB  - The diagnosis of occult hip fracture is frequently missed. We wished to
      investigate if patients in whom occult hip fracture was initially misdiagnosed
      had any distinct features, and their outcome. We reviewed 297 patients who
      presented with hip fractures over a two-year period. There were 24 occult hip
      fractures, the diagnosis was initially missed in 9 patients and correctly made in
      the other 15. Of the correctly identified patients, 8/15 were independently
      mobile and 9/15 were living in their own home compared to 0/9 independently
      mobile and 2/9 living in own home among those with missed diagnosis (p < 0.001).
      Seven of nine patients with a missed diagnosis had mental confusion but none in
      the other 15 (p < 0.001). Eight of the nine patients with missed diagnosis of
      fracture had intra-capsular fractures, of which 6 secondarily displaced. Three of
      those nine patients died within one year from their fracture. We suggest a low
      threshold of investigation for occult hip fracture in the elderly, infirm and
      mentally confused who present to the accident department with suspected occult
      hip fracture.

PMID- 20698457
TI  - Idiopathic anterior knee pain in the young. A prospective controlled trial.
AB  - Idiopathic anterior knee pain is a common condition in adolescents. The aim of
      this study was to compare the biometric parameters such as hamstring tightness,
      hip and knee movements and joint laxity in patients with idiopathic anterior knee
      pain with a control population of similar age and gender. Patients (n = 34) and
      controls (n = 34) (age and sex matched) between the age of 11 and 25 were
      recruited for the study. The mean follow-up of the patient group was 20 months.
      The patients showed a statistically significant improvement in their symptoms (SF
      36 physical component, p = 0.001) despite the fact that half of them did not
      attend physiotherapy sessions. Patients had statistically significant hamstring
      tightness (p = 0.04) and increased external hip rotation (p = 0.001) as compared
      to the control group. These findings support the theory of idiopathic anterior
      knee pain being a self-limiting condition that is associated with hamstring
      tightness.

PMID- 20698456
TI  - Outcome after short intramedullary nail fixation of unstable proximal femoral
      fractures.
AB  - In this study we assess the clinical and radiological outcomes after surgical
      fixation of unstable, extracapsular fractures of the proximal femur using two
      designs of short intramedullary nail. We reviewed 158 patients of which 131 had
      fixation using the Intra Medullary Hip Screw (IMHS original Richards Compression
      Hip Screw design) and 27 with the original design Proximal Femoral Nail (PFN
      Synthes). Outcome measures including non-union, peri-implant fracture, post
      operative function and mortality were similar between groups. Proximal screw cut
      out and consequently re-operation rate were significantly higher for the PFN. A
      number of variables may predispose a patient to develop screw cut-out including
      gender, experience of surgeon, fracture pattern, implant design and tip-apex
      distance. As such a multivariable logistic regression model was used to
      investigate the independent effects of these variables on proximal screw cut-out.
      Only tip-apex distance was found to have a significant association with proximal
      screw cut-out and differences between implant designs could be accounted for by
      surgical technique rather than implant design. The results of this study suggest
      that both implants have similar post-operative outcome measures and complication
      rates when implanted correctly.

PMID- 20698458
TI  - Evaluation of treatment of late-onset tibia vara using gradual angulation
      translation high tibial osteotomy.
AB  - Late-onset tibia vara or Blount's disease is the most common cause of pathologic
      genu varum in children and adolescents. Treatment remains controversial. Many
      studies in the past have shown that an osteotomy with acute correction is the
      most appropriate treatment. More recently however, there has been a growing
      interest, especially in severe cases, in using gradual correction with the
      Ilizarov technique after a single high tibial osteotomy. A retrospective study in
      20 children with late-onset tibia vara, who were treated by gradual angulation
      translation high tibial osteotomy using the Ilizarov technique, was performed.
      The mean follow-up period was 2.9 years (range: 2-4 years; SD 0.75). Recurrence
      of varus deformity to various degrees was noted in 10 of 22 cases (45.5%).
      Recurrence of deformity was found to be significantly related to both the degree
      of pre-operative deviation and the duration of follow-up. No statistically
      significant relationship was found between recurrence and the age of the patients
      at the time of the operation. Angulation translation high tibial osteotomy using
      the Ilizarov technique is a unique method for realignment of the mechanical axis
      in late onset tibia vara. It also allows for correction of associated
      deformities. The rate of recurrence of varus deformity is however relatively
      high.

PMID- 20698459
TI  - Comparative gravimetric wear analysis in mobile versus fixed-bearing posterior
      stabilized total knee prostheses.
AB  - Polyethylene (PE) wear is the limiting factor for the longevity of a conventional
      total knee arthroplasty (TKA). Excessive wear leads to loosening and eventual
      implant failure. The aim of our in vitro study was to investigate wear of a PE
      tibial insert on a rotating platform as compared to the same insert fixed to the
      tibial baseplate and articulating with a similar femoral component. All tests
      were performed at Endolab Laboratories, Rosenheim, Germany using a knee joint
      simulator following ISO 14243-1. Three specific configurations were tested and
      compared to a loaded soak control: (1) the rotating platform using machined
      polyethylene (PE), (2) fixed bearing using machined PE, (3) fixed bearing using
      compression-moulded PE. Calf serum with a high protein concentration of 30 g/l
      was chosen as test lubricant. PE wear was measured gravimetrically using the ISO
      14243-2 protocol. The total wear rates found for all systems tested were low. The
      mean wear rate was 1.40 mg per million cycles for the moulded fixed bearing, 4.07
      mg per million cycles for the machined fixed bearing type and 0.82 mg per million
      cycles for the machined rotating platform bearing type. We conclude that the TKA
      system we tested (Performance, Biomet, Warsaw, IND, USA) demonstrated very low
      gravimetric wear. The wear rate of the same implant in the fixed mode compared to
      the rotating platform mode was four times higher.

PMID- 20698460
TI  - Treatment of solitary bone cysts with allogenic bone graft and platelet-rich
      plasma. A preliminary report.
AB  - The treatment of solitary bone cysts remains controversial. The high recurrence
      rate after operative treatment calls for the search of new effective treatment
      methods. The aim of this study was to evaluate the outcomes of treatment of
      solitary bone cysts with platelet-rich plasma (PRP) and allogenic bone grafts.
      The study group consisted of 9 patients (4 males and 5 females) with the
      diagnosis of solitary bone cyst. Their mean age was 12 years and 2 months (range:
      6 to 17 years). All patients were symptomatic in routine daily activities. There
      was a coexisting fracture within the cyst wall in three patients. The operative
      procedure included removal of the cyst wall soft-tissue lining and filling of the
      cavity with deep frozen, gamma irradiated morselized allogenic bone grafts mixed
      with PRP. The PRP was prepared preoperatively with the GPS System (Gravitational
      Platelet Separation System, Biomet Merck). In six patients with an existing or
      impending fracture in particularly large cysts, fixation was used. For the cysts
      located close to the epiphysis (2 femurs, 1 humerus) we used an IM nail or DHS.
      For three cysts located in the diaphyseal region of the humerus we used an
      Ilizarov fixator. Three cysts with lower risk of impending fracture were left
      without fixation. The mean follow-up period was 19.5 months (range: 12 to 30). We
      noted no procedure-related complications and no refracture during the observation
      period. Bleeding from the wound was minimal, possibly as a result of PPP use. The
      wounds healed without swelling or excessive scar formation. After 12 months all
      the cysts were completely filled with new bone and were staged as Neer stage I.
      All the patients were asymptomatic. The use of PRP with allogenic bone grafts
      appears as a promising method for the treatment of solitary bone cysts. Further
      studies on larger patients series with longer follow-up will be necessary to
      answer the question whether this method will provide a lower recurrence rate
      compared to other forms of treatment.

PMID- 20698461
TI  - Effect of combined administration of transforming growth factor-b1 and insulin
      like growth factor I on the mechanical properties of a patellar tendon defect
      model in rabbits.
AB  - The aim of this study was to test the hypothesis that combined administration of
      TGF-b1 and IGF-I in a patellar tendon defect model could enhance the mechanical
      properties of the healed tendon. Twenty four New Zealand white rabbits were used
      for this purpose. In each animal, the right knee was used for the application of
      the growth factors, whereas the left knee served as an untreated control. The
      growth factors were mixed with fibrin sealant as a delivery vehicle. Two groups
      of rabbits were sacrificed after 2 weeks and 6 weeks respectively. Application of
      the growth factors resulted in a significant increase in force at failure,
      ultimate stress, stiffness, and energy uptake at 2 weeks, whereas none of the
      parameters revealed any significant difference between the two groups at 6 weeks.
      This study provides valuable information on the effect of the two growth factors
      on this patellar tendon defect model.

PMID- 20698462
TI  - Qualitative analysis of substance P, NK1-receptor and nerve ingrowth in substance
      P-treated ruptured rat Achilles tendon.
AB  - Substance P has a stimulating effect on fibroblast proliferation, collagen
      organization, and angiogenesis in ruptured and subsequently sutured rat Achilles
      tendon. This effect is also reflected in the biomechanical properties of the
      tendon. The aim of this study was to substantiate the effect of exogenous
      substance P on endogenous substance P, NK-1 receptor, and nerve ingrowth in an in
      vivo tendon-healing setting. Ninety-six male Sprague-Dawley rats were randomly
      assigned to one of four groups and injected with saline, substance P (10(-6)
      micromol/kg BW and 10(-8) micromol/kg BW) associated with neutral endopeptidase
      inhibitors, or neutral endopeptidase inhibitors alone into the paratendinous
      region of the ruptured and subsequently sutured Achilles tendons from the second
      until the sixth day postoperatively. Substance P, NK-1 receptor, and nerve
      ingrowth (PGP 9.5) were analysed using immunofluorescence at four different time
      points: one, two, four and six weeks postoperatively. In all groups substance P
      was predominantly expressed in the extracellular matrix during the first two
      weeks, corresponding to fibroblast proliferation, and first disappeared from the
      saline group in the proliferative phase. In contrast, substance P was not
      expressed in the blood vessel wall during the first two weeks, when angiogenesis
      was most pronounced. NK-1 receptor was almost always expressed in the blood
      vessel wall and in the extracellular matrix during this period and disappeared
      progressively afterwards. No nerve ingrowth was identified. Exogenously
      administered substance P in sutured rat Achilles tendon rupture does not
      stimulate sensory nerve ingrowth, but seems to have a booster effect on
      endogenous substance P for fibroblast proliferation via autocrine/paracrine
      stimulation.

PMID- 20698463
TI  - Subungual glomus tumours: a technical tip towards diagnosis on plain radiographs.
AB  - Plain radiography can help in confirming the clinical diagnosis of a subungual
      glomus tumour, as erosive changes in the distal phalanx are present in 22% of
      cases. Such changes will be more easily identified on a lateral radiograph with
      the painful finger and its contralateral counterpart pointing toward each other:
      discrete scalloping of the distal phalanx will thus be made more evident.

PMID- 20698464
TI  - Reconstruction of the medial patellofemoral ligament for patellar instability
      using an autologous gracilis tendon graft.
AB  - Patellofemoral dislocations are common. In cases with recurrence or residual
      instability, surgical intervention is usually considered. Numerous treatment
      protocols have been used in the past to treat patellofemoral instability
      secondary to patella dislocation. Reconstruction of the medial patellofemoral
      ligament is one of the possible options, since it was acknowledged to have a
      major medial stabilising role on the patella. We present a technique for
      reconstruction of the medial patellofemoral ligament using an autologous gracilis
      tendon graft.

PMID- 20698465
TI  - Non-traumatic avulsion of the greater trochanter: a case report.
AB  - Apophyseal fracture affecting the greater trochanter is a rare injury in
      children. We report a case of non traumatic avulsion of the greater trochanter in
      a 13-year-old boy who presented with a history of pain about his right hip over
      the past few months. Hip radiographs, radioisotope bone scan and CT scan
      confirmed the diagnosis of avulsion of the greater trochanter with minimal
      displacement. The symptoms resolved after percutaneous in situ lag screw
      fixation. Radiographs 18 months after treatment showed fusion of the trochanteric
      physis.

PMID- 20698466
TI  - Navicular stress fracture in high-performing twin brothers: a case report.
AB  - Navicular stress fractures mainly occur in sprinting and push-off athletes.
      Numerous predisposing factors have been implicated in their development. Within a
      six-week interval in the summer of 2009, twin brothers, both elite track and
      field athletes, presented to us with medial foot pain. Plain radiographs were
      negative but a radioisotope bone scan and CT scan revealed an incomplete
      navicular fracture in both of them. The fracture was typically located in the
      proximal dorsal cortex of the central portion of the navicular bone. The presence
      of such a stress fracture in high performing, monozygotic twins, has never been
      described. As extrinsic and intrinsic risk factors, their comparability of
      mechanical stresses and kinematics as well as a genetic predisposition can be put
      forward. This case report suggests that a complex interaction between mechanical
      and genetic risk factors exists in the development of navicular stress fractures.

PMID- 20698467
TI  - Ankylosing spondylitis: inadvertent application of a rigid collar after cervical
      fracture, leading to neurological complications and death.
AB  - Ankylosing spondylitis is a seronegative spondyloarthropathy which predominantly
      affects the sacroiliac joints and the spine. The spine can become very kyphotic
      with time. Minor trauma is sufficient to produce a fracture, because of the
      underlying osteoporosis and because the ankylosed segments constitute large
      leverage arms. These fractures are unstable because the soft tissues are ossified
      and also involved in the fracture. Cervical spine fractures need an
      immobilisation which respects the pre-injury flexion deformity. Inadvertent
      application of a rigid collar which forces the previously flexed cervical spine
      into extension may lead to neurological deterioration and even death. We report
      such a case in a 59-year-old male patient.

PMID- 20698468
TI  - Recurrent chordoma of the L2 vertebra: a case report.
AB  - Chordoma is a rare slow-growing, locally invasive primary malignant bone tumour
      arising from notochord remnants. It is characterised by a high local recurrence
      rate. Most chordomas (60%) are found in the sacrococcygeal region: only 15%
      originate in the mobile spine. CT-scan and MRI can help evaluate the tumour
      extension. En bloc resection of the tumour mass is the standard treatment. The
      main prognostic factor is tumour-negative surgical margins. Due to the location
      of spinal chordomas, adjacent to vital neural and vascular structures, this can
      be difficult to achieve. Therefore radiotherapy has been used when adequate
      excision is not possible and in case of local recurrence. We report the case of a
      72-year-old female with a recurrent chordoma of the L2 vertebra, previously
      treated with resection and radiotherapy. The recurrent chordoma was resected
      using a right-sided thoraco-phreno-laparotomy as the tumour could not be resected
      using the left anterior approach or posterior approach due to extensive fibrosis
      following surgery and radiotherapy.

PMID- 20698469
TI  - What visual information is used for stereoscopic depth displacement
      discrimination?
AB  - There are two ways to detect a displacement in stereoscopic depth, namely by
      monitoring the change in disparity over time (CDOT) or by monitoring the
      interocular velocity difference (IOVD). Though previous studies have attempted to
      understand which cue is most significant for the visual system, none has designed
      stimuli that provide a comparison in terms of relative efficiency between them.
      Here we used two-frame motion and random-dot noise to deliver equivalent
      strengths of CDOT and IOVD information to the visual system. Using three kinds of
      random-dot stimuli, we were able to isolate CDOT or IOVD or deliver both
      simultaneously. The proportion of dots delivering CDOT or IOVD signals could be
      varied, and we defined the discrimination threshold as the proportion needed to
      detect the direction of displacement (towards or away). Thresholds were similar
      for stimuli containing CDOT only, and containing both CDOT and IOVD, but only one
      participant was able to consistently perceive the displacement for stimuli
      containing only IOVD. We also investigated the effect of disparity pedestals on
      discrimination. Performance was best when the displacement crossed the reference
      plane, but was not significantly different for stimuli containing CDOT only and
      those containing both CDOT and IOVD. When stimuli are specifically designed to
      provide equivalent two-frame motion or disparity-change, few participants can
      reliably detect displacement when IOVD is the only cue. This challenges the
      notion that IOVD is involved in the discrimination of direction of displacement
      in two-frame motion displays.

PMID- 20698470
TI  - Expertise and the spatio-temporal characteristics of anticipatory information
      pick-up from complex movement patterns.
AB  - Groups of high- (n = 14), intermediate- (n = 12), and low-skilled (n = 15)
      cricket batsmen participated in two experiments to examine expertise-related
      differences in anticipatory information pick-up that combined temporal and
      spatial occlusion methodologies. In experiment 1 participants were shown video
      displays of a bowler delivering one of three different types of delivery with the
      display manipulated so that only selected local features of the bowler's movement
      pattern (bowling hand, bowling hand and arm, trunk, lower body, or whole body)
      were visible and then only for specific time periods prior to ball release. Only
      the highly-skilled players were able to produce better-than-chance predictions of
      ball type and then only under a limited set of display conditions. Information
      from bowling hand and arm cues was particularly critical although continuous
      visibility of these cues was apparently not essential for information pick-up. In
      experiment 2 the order in which particular features were made visible throughout
      the bowler's movement pattern was varied in an attempt to find the sequence of
      cues that was most favourable for effective information pick-up. The necessity in
      this experiment to switch vision between different features eliminated the highly
      skilled players' capability to anticipate. Expert anticipation is dependent on
      sensitivity to information arising from a select set of local cues, and forced
      attentional switches between different cues negate effective information pick-up
      and, with it, the expert advantage.

PMID- 20698471
TI  - Visual processing asymmetries in change detection.
AB  - Change detection is critically dependent on attentional mechanisms. However, the
      relation between an asymmetrical distribution of visuo-spatial attention and the
      detection of changes in visual scenes is not clear. Spatial tasks are known to
      induce a stronger activation of the right hemisphere. The effects of such visual
      processing asymmetries induced by a spatial task on change detection were
      investigated. When required to detect changes in the left and in the right visual
      fields, participants were significantly faster in detecting changes on the left
      than on the right. Importantly, this left-side superiority in change detection is
      not influenced by inspection time, suggesting a critical role of visual
      processing benefit for the left visual field.

PMID- 20698472
TI  - Effect of scene dimensionality on colour constancy with real three-dimensional
      scenes and objects.
AB  - The effect of scene dimensionality on colour constancy was tested with real
      scenes and objects. Observers viewed a three-dimensional (3-D) scene, or its two
      dimensional (2-D) planar projection, through a large beam-splitter that projected
      the virtual image of a real test object (a cube or its 2-D projection) so that it
      appeared part of the scene. Test object and scene could be illuminated
      independently with high chromatic precision. In each trial, the illuminance of
      the scene changed abruptly from 25000 K to 6700 K and the illuminant of the test
      object changed either consistently or inconsistently with it by a variable
      quantifiable amount. Observers had to decide whether the test object underwent a
      change in its materials. The extent of constancy obtained in the experiment was
      not influenced by scene dimensionality and varied significantly with the colour
      of the test object. These results suggest that color constancy in the conditions
      tested here may be determined by local spectral quantities.

PMID- 20698473
TI  - Exploring the perceptual causes of search set-size effects in complex scenes.
AB  - We explored search set-size effects in the context of scenes, where objects are
      difficult to delineate and define. Observers searched for a tank target in
      landscape scenes populated by boulder, shrub, and tree distractors, which varied
      in their color and size similarity to the target. Scenes contained either 75 or
      125 distractors. In two experiments we found that adding boulder or shrub
      distractors that were similar to the target in color and in size produced a
      consistent set-size effect, but adding distractors that were similar to the
      target only in size did not. Tree distractors, which were larger than the target,
      also produced a set-size effect regardless of whether they had a target-similar
      color (experiment 1) or not (experiment 2). In a third experiment we varied
      target-tree color similarity and tree color heterogeneity and found no change in
      search efficiency. We interpret these data as evidence for two independent
      sources of set-size effects in scenes, one subject to target--distractor
      similarity relationships (shrubs/boulders) and the other reflecting overall
      visual clutter (trees), with these latter clutter effects definable by edge
      content.

PMID- 20698474
TI  - Learning perceptual organization in infancy: the effect of simultaneous versus
      sequential variability experience.
AB  - Infants do not readily organize using form similarity: 6- to 7-month-olds
      familiarized with horizontal or vertical bars (filled rectangles) do not display
      a subsequent preference for a novel column versus row organization of X-O
      elements (Quinn and Bhatt, 2006 Journal of Experimental Psychology: Human
      Perception and Performance 32 1221-1230). In experiment 1, infants were
      familiarized with more complex bars composed of beads or crosshatches, and
      performance was again unsuccessful. In experiment 2, all three bar types were
      presented during familiarization and infants performed successfully, indicating
      that variability in pattern information depicting an invariant structure enhances
      the learning of perceptual organization. In experiment 3, we examined whether the
      manner in which variability is experienced (simultaneous versus sequential
      contrast) impacts this learning. One group of infants was familiarized with a
      single pattern containing the three different bar types (within-trial
      variability), and another was presented with the same three bar types, but with
      each appearing on a different trial (across-trial variability). Only the across
      trial variability group performed successfully, suggesting that trial-to-trial
      change in local element information induced by sequential presentation is a
      significant factor in facilitating the learning of perceptual organization.

PMID- 20698475
TI  - Perceptual factors affecting the ability to assess facial resemblance between
      parents and newborns in humans.
AB  - People undeniably pay attention to faces, and facial resemblance may act as a
      kinship cue. However, previous studies have shown that the ability to detect
      kinship through facial resemblance is limited, and it has been suggested that
      this may be due to several types of perceptual factors. To further understand the
      processes that underpin kinship judgment, it is important to investigate which
      perceptual factors predict the probability of parent-child pairs being detected
      as related. To this end, we performed two experiments. In the first, we evaluated
      the ability of human observers to match newborns with one of their parents. In
      the second, we explored three perceptual factors that may have influenced kinship
      detection (gender discrimination, facial attractiveness, and perceptual
      similarity). Results showed that the participants were able to match newborns
      with one of their parents, even though the task was perceived as difficult.
      Moreover, our study goes further than previous findings, showing that the
      perceptual factors investigated may significantly contribute to kinship
      detection.

PMID- 20698476
TI  - The function and specificity of sensitivity to cues to facial identity: an
      individual-differences approach.
AB  - The expertise of adults in recognising the identity of individual faces has been
      attributed to their exquisite sensitivity to differences among faces in the
      spacing of features (second-order relations). However, the reliability of
      individual differences and the extent to which this sensitivity predicts
      individuals' ability to recognise faces has not been tested directly. We
      administered two sets of tasks to adult females (n = 31); the tests were
      separated by 2 to 11 days. Individual differences in sensitivity to the spacing
      of facial features were reliable across days and correlated with individual
      differences in sensitivity to the spacing of features (doors and windows) in
      houses, but did not predict accuracy when participants matched facial identity
      across changes in point of view. Individual differences in sensitivity to
      featural cues to facial identity were not reliable, likely because of ceiling
      effects. The function and specificity of sensitivity to the spacing of features
      is discussed.

PMID- 20698477
TI  - Visual capture of action, experience of ownership, and the illusion of self
      touch: a new rubber hand paradigm.
AB  - A new rubber hand paradigm evokes an illusion with three conceptually distinct
      components: (i) the participant experiences her/his hidden right hand as
      administering touch at the location of the examiner's viewed administering hand
      (visual capture of action); (ii) the participant experiences the examiner's
      administering hand as being the participant's own hand (experience of ownership);
      and (iii) the participant experiences her/his two hands as being in contact, as
      if she/he were touching her/his own hand (illusion of self-touch). The presence
      of these illusory experiences was confirmed by questionnaire responses and
      proprioceptive drift data.

PMID- 20698478
TI  - Now you feel it, now you don't: how robust is the phenomenon of illusory tactile
      experience?
AB  - Recent studies have reported that in normal healthy individuals, the perception
      of illusory sensations in one modality can be induced by the presentation of a
      stimulus in another modality. These illusory sensations may arise from the
      activation of a tactile representation in memory induced by the non-target
      stimulus, in a process mirroring that thought to be responsible for many forms of
      medically unexplained symptoms. The reliability of illusory-touch reports was
      investigated here in two experiments with a novel perceptual paradigm designed to
      simulate the occurrence of somatoform symptoms in the laboratory. A concurrent
      light significantly increased the number of tactile stimuli reported, and
      resulted in a higher number of illusory-touch reports, while the modality of the
      trial start cue did not affect subsequent responses. In addition, a strong
      relationship was found between the rates of illusory sensations that participants
      produced in successive sessions, indicating that the tendency to report illusory
      sensations is a robust phenomenon.

PMID- 20698479
TI  - Cross-modal influences on representational momentum and representational gravity.
AB  - Effects of cross-modal information on representational momentum and on
      representational gravity (ie on displacement of remembered location in the
      direction of target motion or in the direction of gravitational attraction,
      respectively) were examined. In experiment 1, ascending or descending visual
      motion (in the picture plane) was paired with ascending or descending auditory
      motion (in frequency space); motion was congruent (both ascending, both
      descending) or incongruent (one ascending, one descending). Memory for visual
      location or auditory pitch was probed. Congruence resulted in larger forward
      displacement for auditory pitch, but did not influence forward displacement for
      visual location. In experiment 2, horizontal visual motion was paired with
      ascending, descending, or no auditory motion. Memory for visual location was
      displaced downward with descending or no auditory motion, and downward
      displacement was larger for visual motion paired with descending auditory motion
      than for visual motion paired with ascending auditory motion. Effects of cross
      modal information on displacement suggest representational momentum and
      representational gravity reflect high-level processing.

PMID- 20698480
TI  - Perceptual compromise between apparent and veridical motion indices: the
      unchained-dots illusion.
AB  - A new motion illusion based on dot-trajectory misperception is presented. The
      illusory effect can not be explained by the aperture problem unlike some previous
      illusions characterised by misperception of motion direction. We propose an
      explanation in terms of 'perceptual compromise' between an original type of
      apparent motion and the veridical motion. Several demonstrations are presented in
      support of that hypothesis.

PMID- 20698482
TI  - Concise approach toward tetrazolo[1,5-a][1,4]benzodiazepines via a novel
      multicomponent isocyanide-based condensation.
AB  - A novel and efficient method for the synthesis of heteroannulated
      [1,4]benzodiazepines via an isocyanide-based multicomponent reaction is reported.
      The tetrazolo[1,5-a][1,4]benzodiazepines were obtained by a facile azide Ugi five
      center four-component reaction (U-5C-4CR) using ketones, sodium azide, ammonium
      chloride, and corresponding isocyanide. The aforementioned tetrazolodiazepines
      represent a notable class of compounds with proven platelet aggregation
      inhibitory and cholecystokinin agonist activities.

PMID- 20698483
TI  - Size dependence in hexagonal mesoporous germanium: pore wall thickness versus
      energy gap and photoluminescence.
AB  - A series of hexagonal mesoporous germanium semiconductors with tunable wall
      thickness is reported. These nanostructures possess uniform pores of 3.1-3.2 nm,
      wall thicknesses from 1.3 to 2.2 nm, and large internal BET surface area in the
      range of 404-451 m(2)/g. The porous Ge framework of these materials is assembled
      from the templated oxidative self-polymerization of (Ge(9))(4-) Zintl clusters.
      Total X-ray scattering analysis supports a model of interconnected deltahedral
      (Ge(9))-cluster forming the framework and X-ray photoelectron spectroscopy
      indicates nearly zero-valence Ge atoms. We show the controllable tuning of the
      pore wall thickness and its impact on the energy band gap which increases
      systematically with diminishing wall thickness. Furthermore, there is room
      temperature photoluminescence emission which shifts correspondingly from 672 to
      640 nm. The emission signal can be quenched via energy transfer with organic
      molecules such as pyridine diffusing into the pores.

PMID- 20698484
TI  - Fabrication of diverse metallic nanowire arrays based on block copolymer self
      assembly.
AB  - Metallic nanowires are useful for fabricating highly integrated nanoscale
      electrical, magnetic, and photonic devices. However, conventional methods based
      on bottom-up growth techniques are subject to concerns such as broad
      distributions in their dimension as well and difficulties in precise placement of
      the nanowires. These issues can be solved by the guided self-assembly of block
      copolymer thin films that can produce periodic arrays of monodisperse nanoscale
      features with excellent positional accuracy. Here, we report transfer of high
      quality linear block copolymer patterns into various metals, Ti, W, Pt, Co, Ni,
      Ta, Au, and Al, to fabricate highly ordered nanowire arrays with widths down to 9
      nm. This novel patterning process does not require specific film deposition
      techniques or etch-chemistries. We also describe their structural, magnetic, and
      electrical properties.

PMID- 20698485
TI  - Stereoselective spirolactam synthesis via palladium catalyzed arylative allene
      carbocyclization cascades.
AB  - A diastereoselective arylative carbocyclization of pro-nucleophile-linked allenes
      with aryl and heteroaryl halides to provide spirocyclic lactam products with
      moderate to high diastereoselectivities and good yields under Pd(0) catalysis is
      reported. Being operationally simple and tolerant of multiple points of
      diversity, this complexity building reaction cascade, in which two new carbon
      carbon bonds and one new heterocyclic ring are created, should be of high value
      in both complex natural product synthesis as well as compound library synthesis.

PMID- 20698486
TI  - Pd-catalyzed regioselective iminothiolation of alkynes: a remarkable effect of
      the CF3 group of iminosulfides.
AB  - Pd-catalyzed iminothiolation of alkynes took place to afford 4-SR substituted 1
      azadienes regioselectively.

PMID- 20698487
TI  - Synthesis of the isoquinocycline-pyrrolopyrrole substructure.
AB  - The synthesis of the pyrrolopyrrole substructure of the isoquinocyclines is
      reported. The pentacyclic (CDEFG) substructure of isoquinocycline A and B, which
      contains an unusual 2,4,5,6-tetrahydropyrrolo[2,3-b]pyrrole (FG) connected via an
      N,O-spiro acetal to the anthraquinoid core of the isoquinocycline aglycon has
      been synthesized. Key steps were a nickel(0)-mediated hydrocyanation of an
      alkynone, the conversion of an O,O-acetal into an N,O-acetal, and an
      intramolecular amidine alkylation.

PMID- 20698488
TI  - Synthesis of 5-amino-oxazole-4-carboxylates from alpha-chloroglycinates.
AB  - Aluminum-based Lewis acids are effective promoters of the condensation of alpha
      chloroglycinates with isonitriles or with cyanide ion, leading to the formation
      of 5-amino-oxazoles.

PMID- 20698489
TI  - Sensitive determination of concentration of nonfluorescent species in an extended
      nano channel by differential interference contrast thermal lens microscope.
AB  - A photothermal detector, named differential interference contrast thermal lens
      microscope (DIC-TLM), was used to determine the concentration of a nonfluorescent
      solution in a nanochannel. This method exploits a local change in the refractive
      index of a solution caused by light absorption. A solution was introduced into a
      100-nm scale channel by a pressure-driven nanofluidic control system and its
      concentration was determined by DIC-TLM. The limit of detection (LOD) was 2.4
      microM in a nanochannel that was 21 microm wide and 500 nm deep. The LOD was 3
      orders of magnitude smaller than that of conventional method. Moreover, the
      detection volume was accurately determined to be merely 0.25 fL by using a
      nanochannel with an optical path length of 500 nm. Based on these results, the
      number of detected molecules was calculated to be 390. In addition, the
      concentration of a solution in a nanochannel that was 790 nm wide and 500 nm deep
      could be determined. Finally, the relationship between sensitivity and channel
      size was investigated and the sensitivity was found to decrease with decreasing
      nanochannel size, which indicates that the changes in the refractive indices of
      water and silica cancel each other out. The DIC-TLM realizes sensitive detection
      of nonfluorescent species in nanochannels without requiring any special
      fabrication techniques. Therefore, DIC-TLM is expected to be a highly useful
      analytical technique in nanofluidics.

PMID- 20698490
TI  - Asymmetric direct alkynylation catalyzed by chiral Ru-bis(oxazolinyl)phenyl
      complexes.
AB  - Propargylic alcohols were obtained with excellent enantioselectivities in the
      asymmetric direct alkynylation of aldehydes using 5 mol % of chiral ruthenium
      complexes containing the chiral bis(oxazolinyl)phenyl ligand.

PMID- 20698491
TI  - Physicochemical stability of the antibody-drug conjugate Trastuzumab-DM1: changes
      due to modification and conjugation processes.
AB  - In the manufacture of the antibody-drug conjugate Trastuzumab-DM1 (T-DM1), the
      lysine residues on the antibody trastuzumab (Tmab) are modified to form the
      intermediate Tmab-MCC (T-MCC) and then conjugated with the drug DM1. Our goal is
      to understand the effects of modification and conjugation steps on the
      physicochemical stability of the antibody. The structural stability of Tmab
      relative to its modified and conjugated forms was assessed, employing thermally
      induced stress conditions to formulations containing Tmab, T-MCC, and T-DM1. DSC,
      SEC, CE-SDS, and LC-MS were used to study the stability of Tmab, T-MCC, and T-DM1
      to thermal stress. The DSC thermograms show a decrease in melting temperature for
      the CH2 transition, in the order Tmab > T-MCC > T-DM1. As per SEC analysis, a
      significant increase in level of aggregation was detected in T-MCC (~32%) and T
      DM1 (~5%) after 14 days at 40  degrees C. Tmab did not show significant aggregate
      formation. CE-SDS and LC-MS data demonstrate that the aggregation in the case of
      T-MCC is largely covalent and involves mechanisms other than formation of
      intermolecular disulfide cross-links. The aggregation observed for T-MCC was
      significantly inhibited upon addition of amino acids with nucleophilic side
      chains containing thiol (Cys) and hydroxyl moieties (Ser, Tyr). The covalent
      aggregation observed for T-MCC and the ability of nucleophilic amino acids,
      particularly Cys, to inhibit it indicate that the maleimide moiety in the MCC
      linker may react to form intermolecular covalent cross-links between T-MCC
      molecules, possibly through a Michael addition mechanism. In addition, DSC
      results demonstrate that the conjugation of the drug moiety DM1 to Tmab results
      in destabilization of the CH2 domain of the antibody.

PMID- 20698493
TI  - A computational study of the potential energy surface of peroxyformic acid
      dimers.
AB  - MP2 and M05-2x calculations with aug-cc-pVDZ basis sets were used to analyze
      intermolecular interactions in peroxyformic acid dimers. A total of 18 and 16
      minima were located on the potential energy surface of HOOCHO dimer complexes at
      M05-2x and MP2 computational levels, respectively. The BSSE corrected interaction
      energies are in a range between 9 and 34 kJ mol(-1) at the MP2/aug-cc-pVDZ
      computational level. The atoms-in-molecules (AIM) theory was also applied to
      explain the nature of the complexes. The interaction energies have been
      partitioned with the natural energy decomposition analysis (NEDA) showing that
      the most important attractive term corresponds to the charge transfer.

PMID- 20698494
TI  - Characterization of composition C4 explosives using time-of-flight secondary ion
      mass spectrometry and X-ray photoelectron spectroscopy.
AB  - The application of surface analytical techniques such as time-of-flight secondary
      ion mass spectrometry (ToF-SIMS) and X-ray photoelectron spectroscopy (XPS) is
      explored as a means of differentiating between composition C4 plastic explosives
      (C-4). Three different C-4 samples including U.S. military grade C-4, commercial
      C-4 (also from the United States), and C-4 from England (PE-4) were obtained and
      analyzed using both ToF-SIMS and XPS. ToF-SIMS was able to successfully
      discriminate between different C-4 samples with the aid of principal component
      analysis, a multivariate statistical analysis approach often used to reduce the
      dimensionality of complex data. ToF-SIMS imaging was also used to obtain
      information about the spatial distribution of the various additives contained
      within the samples. The results indicated that the samples could potentially be
      characterized by their 2-D chemical and morphological structure, which varied
      from sample to sample. XPS analysis also showed significant variation between
      samples, with changes in the atomic concentrations, as well as changes in the
      shapes of the high-resolution C 1s and O 1s spectra. These results clearly
      demonstrate the feasibility of utilizing both ToF-SIMS and XPS as tools for the
      direct characterization and differentiation of C-4 samples for forensic
      applications.

PMID- 20698492
TI  - Plasma proteome response to severe burn injury revealed by 18O-labeled
      "universal" reference-based quantitative proteomics.
AB  - A burn injury represents one of the most severe forms of human trauma and is
      responsible for significant mortality worldwide. Here, we present the first
      quantitative proteomics investigation of the blood plasma proteome response to
      severe burn injury by comparing the plasma protein concentrations of 10 healthy
      control subjects with those of 15 severe burn patients at two time-points
      following the injury. The overall analytical strategy for this work integrated
      immunoaffinity depletion of the 12 most abundant plasma proteins with cysteinyl
      peptide enrichment-based fractionation prior to LC-MS analyses of individual
      patient samples. Incorporation of an 18O-labeled "universal" reference among the
      sample sets enabled precise relative quantification across samples. In total, 313
      plasma proteins confidently identified with two or more unique peptides were
      quantified. Following statistical analysis, 110 proteins exhibited significant
      abundance changes in response to the burn injury. The observed changes in protein
      concentrations suggest significant inflammatory and hypermetabolic response to
      the injury, which is supported by the fact that many of the identified proteins
      are associated with acute phase response signaling, the complement system, and
      coagulation system pathways. The regulation of approximately 35 proteins observed
      in this study is in agreement with previous results reported for inflammatory or
      burn response, but approximately 50 potentially novel proteins previously not
      known to be associated with burn response or inflammation are also found.
      Elucidating proteins involved in the response to severe burn injury may reveal
      novel targets for therapeutic interventions as well as potential predictive
      biomarkers for patient outcomes such as multiple organ failure.

PMID- 20698495
TI  - Combined use of optical and electron microscopic techniques for the measurement
      of hygroscopic property, chemical composition, and morphology of individual
      aerosol particles.
AB  - In this work, an analytical method for the characterization of the hygroscopic
      property, chemical composition, and morphology of individual aerosol particles is
      introduced. The method, which is based on the combined use of optical and
      electron microscopic techniques, is simple and easy to apply. An optical
      microscopic technique was used to perform the visual observation of the phase
      transformation and hygroscopic growth of aerosol particles on a single particle
      level. A quantitative energy-dispersive electron probe X-ray microanalysis, named
      low-Z particle EPMA, was used to perform a quantitative chemical speciation of
      the same individual particles after the measurement of the hygroscopic property.
      To validate the analytical methodology, the hygroscopic properties of
      artificially generated NaCl, KCl, (NH(4))(2)SO(4), and Na(2)SO(4) aerosol
      particles of micrometer size were investigated. The practical applicability of
      the analytical method for studying the hygroscopic property, chemical
      composition, and morphology of ambient aerosol particles is demonstrated.

PMID- 20698496
TI  - Probing the function of nucleotides in the catalytic cores of the 8-17 and 10-23
      DNAzymes by abasic nucleotide and C3 spacer substitutions.
AB  - 8-17 and 10-23 are the two most comprehensively studied RNA-cleaving DNAzymes to
      date and have the ability to carry out sequence-specific cleavage of both all-RNA
      or chimeric RNA/DNA substrates. Mutagenesis studies of 8-17 and 10-23 DNAzymes
      using alternative natural nucleotides to substitute a given nucleotide in the
      DNAzyme sequence have found that both DNAzymes are able to tolerate a variety of
      alterations at many sequence locations. Chemical modification studies employing
      nucleotides containing nonnatural nucleobases have led to findings that some
      specific entities of selected nucleobases are irreplaceable by other functional
      groups. In this work, we set out to carry out a mutagenesis study on both 8-17
      and 10-23 by substituting individual nucleotides in their catalytic cores with a
      baseless (abasic) nucleotide or a baseless/sugarless nucleotide containing only
      acyclic C3 spacer. We observed that the substitution with an abasic nucleotide or
      C3 spacer at many locations within the catalytic core of both 8-17 and 10-23 was
      still able to support a significant level of catalytic activity of each DNAzyme,
      suggesting that both DNAzymes have considerable structural plasticity to maintain
      their catalytic functions. We also observed that almost all nucleobases in the
      catalytic core of each DNAzyme appeared to make either an absolutely essential
      contribution to the function of each DNAzyme or exhibit a "chaperone-like"
      activity that is important for the optimal function of each DNAzyme; in contrast,
      only one sugar ring in 8-17 and four in 10-23 were inferred to make some
      contribution to the optimal function of the relevant DNAzyme. Finally, our study
      also raised a possibility that the 10-23 DNAzyme might be a special structural
      variant of the larger 8-17 DNAzyme family.

PMID- 20698497
TI  - Highly sensitive and stable electrochemical sulfite biosensor incorporating a
      bacterial sulfite dehydrogenase.
AB  - This paper describes a highly sensitive electrochemical (voltammetric)
      determination of sulfite using a combination of Starkeya novella sulfite
      dehydrogenase (SDH), horse heart cytochrome c (cyt c), and a self-assembled
      monolayer of 11-mercaptoundecanol (MU) cast on a gold electrode. The biosensor
      was optimized in terms of pH and the ratio of cyt c/SDH. The electrocatalytic
      oxidation current of sulfite increased linearly from 1 to 6 microM at the enzyme
      modified electrode with a correlation coefficient of 0.9995 and an apparent
      Michaelis constant (K(M,app)) of 43 microM. Using an amperometric method, the low
      detection limit for sulfite at the enzyme-modified electrode was 44 pM (signal-to
      noise ratio = 3). The modified electrode retained a stable response for 3 days
      while losing only ca. 4% of its initial sensitivity during a 2 week storage
      period in 50 mM Tris buffer solution at 4 degrees C. The enzyme electrode was
      successfully used for the determination of sulfite in beer and white wine
      samples. The results of these electrochemical analyses agreed well with an
      independent spectrophotometric method using Ellman's reagent, but the detection
      limit was far superior using the electrochemical method.

PMID- 20698498
TI  - Multifunctional au nanoparticle dendrimer-based surface plasmon resonance
      biosensor and its application for improved insulin detection.
AB  - Bifunctional hydroxyl/thiol-functionalized fourth-generation polyamidoamine
      dendrimer (G4-PAMAM)-encapsulated Au nanoparticle (NP) was synthesized and
      immobilized on a mixed self-assembled monolayer (SAM)-modified gold surface. This
      modified surface was resistant to nonspecific adsorption of proteins having a
      wide range of molecular weight and isoelectric points. Part of the dendrimer
      thiol groups were converted to hydrazide functionalities providing an activated
      surface available to subsequently immobilize the receptor for developing a sensor
      surface to immunoaffinity reaction. Herein, the surface plasmon resonance (SPR)
      detection of insulin was obtained by means of a competitive immunoassay
      principle. The resulting Au NP dendrimer-modified surface provided an assay with
      high stability, significantly enhanced sensitivity, and a detection limit for
      analyzing insulin of 0.5 pM. The SPR detection of insulin was amplified due to
      the changes in the dielectric properties of the matrixes, occurring upon the
      biorecognition processes on the sensor surface, through the coupling of the
      localized plasmon of the NPs with the surface plasmon wave. The developed sensor
      chip was used to analyze insulin in human serum samples from healthy and diabetic
      patients. The results showed good correlation to the reference method. The
      specificity and the improved sensitivity of this biosensing platform could have
      significant implications for the detection of a wide range of molecules and
      biomarkers in complex biological media.

PMID- 20698500
TI  - Total synthesis of pareitropone via radical anion coupling.
AB  - A concise (9-step) synthesis of the tropoloisoquinoline alkaloid pareitropone has
      been achieved starting from 2-bromoisovanillin. The key step features oxidative
      cyclization of a readily available phenolic nitronate for the convenient
      construction of the fused tropone ring. This work underscores the synthetic
      utility of intramolecular oxidative coupling reactions of phenolic nitronates.

PMID- 20698499
TI  - Characterization of surface-exposed reactive cysteine residues in Saccharomyces
      cerevisiae.
AB  - Numerous cellular processes are subject to redox regulation, and thiol-dependent
      redox control, acting through reactive cysteine (Cys) residues, is among the
      major mechanisms of redox regulation. However, information on the sets of
      proteins that provide thiol-based redox regulation or are affected by it is
      limited. Here, we describe proteomic approaches to characterize proteins that
      contain reactive thiols and methods to identify redox Cys in these proteins.
      Using Saccharomyces cerevisiae as a eukaryotic model organism, we identified 284
      proteins with exposed reactive Cys and determined the identities of 185 of these
      residues. We then characterized subsets of these proteins as in vitro targets of
      major cellular thiol oxidoreductases, thioredoxin and glutaredoxin, and found
      that these enzymes can control the redox state of a significant number of thiols
      in target proteins. We further examined common features of exposed reactive Cys
      and compared them with an unbiased control set of Cys using computational
      approaches. This analysis (i) validated the efficacy of targeting exposed Cys in
      proteins in their native, folded state, (ii) quantified the proportion of targets
      that can be redox regulated via thiol oxidoreductase systems, and (iii) revealed
      the theoretical range of the experimental approach with regard to protein
      abundance and physicochemical properties of reactive Cys. From these analyses, we
      estimate that approximately one-fourth of exposed Cys in the yeast proteome can
      be regarded as functional sites, either subject to regulation by thiol
      oxidoreductases or involved in structural disulfides and metal binding.

PMID- 20698501
TI  - Structural mass spectrometry in protein therapeutics discovery.
AB  - The protein therapeutics market is one of the highest growing segments of the
      pharmaceutical industry with an estimated global market value of $77 billion by
      2011 (Global Protein Therapeutics Market report by RNCOS: Delhi, India, 2009).
      This growth has been fueled by several advantages that protein drugs can offer
      such as higher specificity, reduced side effects, and faster development time
      compared to small molecule drugs. Major pharmaceutical companies are
      strategically shifting gears toward protein therapeutics and gradually increasing
      the biologics portion of their pipelines. Consequently, in the present
      pharmaceutical industry, there is a rapid growth in the number and types of
      protein structural mass spectrometry analyses, particularly during the discovery
      phase where an abundance of new drug candidates are being investigated. This
      perspective article discusses the role of protein structural mass spectrometry
      during the discovery of protein therapeutics with focus on recombinant protein
      production quality control and structural biology applications. The current
      challenges in technologies associated with this field and the analytical
      prospects for the future direction will be also discussed.

PMID- 20698503
TI  - Highly efficient and expedient synthesis of 5-hydroxy-1H-pyrrol-2-(5H)-ones from
      FeCl3-catalyzed tandem intramolecular enaminic addition of tertiary enamides to
      ketones and 1,3-hydroxy rearrangement.
AB  - Catalyzed by FeCl(3) under very mild conditions, tertiary enamides underwent a
      highly efficient intramolecular enaminic addition reaction to the ketonic
      carbonyls followed by 1,3-hydroxy rearrangement to produce 5-hydroxy-1H-pyrrol
      2(5H)-ones in excellent yields.

PMID- 20698504
TI  - Preparation and characterization of (CNSSS)2(A)2 (A = AsF6(-), SbF6(-), Sb2F11(
      )) containing the O2-like 5,5'-bis(1,2,3,4-trithiazolium) dication: the second
      example of a simple nonsterically hindered main-group diradical that retains its
      paramagnetism in the solid state.
AB  - The reaction of NC-CN with a 1:1 mixture of S(4)(MF(6))(2) and S(8)(MF(6))(2) (M
      = As, Sb) (stoichiometrically equivalent to four "S(3)MF(6)" units) results in
      the quantitative formation of S(3)NCCNS(3)(MF(6))(2) [7(MF(6))(2)], which is the
      thermodynamic sink in this reaction. The Sb(2)F(11)(-) salt 7(Sb(2)F(11))(2) is
      prepared by the addition of an excess of SbF(5) to 7(AsF(6))(2). Crystal
      structure determinations for all three salts show that 7(2+) can be viewed as two
      R-CNS(3)(+) radical cations joined together by a C-C single bond. The two rings
      are coplanar and in a trans orientation due to electrostatic N(delta
      )...S(delta+) interactions. The classically bonded alternative (quinoidal
      structure), in which the octet rule is obeyed, is not observed and is much higher
      in energy based on calculated estimates and a simple comparison of pi bond
      energies. Calculated molecular orbitals (MOs) support this, showing that the MO
      corresponding to the quinoidal structure lies higher in energy than the nearly
      degenerate singly occupied MOs of 7(2+). The vibrational spectra of 7(2+) in all
      salts were assigned based on a normal-coordinate analysis and theoretical
      vibrational frequencies calculated at the PBE0/6-31G* level. In the solid state,
      7(2+) is a planar disjoint diradical with essentially degenerate open-shell
      singlet and triplet states. The disjoint nature of the diradical cation 7(2+) is
      established by magnetic susceptibility studies of the Sb(2)F(11)(-) salt doped in
      an isomorphous diamagnetic host material (CNSNS)(2)(Sb(2)F(11))(2)
      [10(Sb(2)F(11))(2)]. Intramolecular spin coupling is extremely weak corresponding
      to a singlet-triplet gap (DeltaE(ST) = 2J) of <+/-2 cm(-1). CASPT2[12,12]/6-311G*
      calculations support a triplet ground state with a small singlet-triplet gap. The
      single-crystal electron paramagnetic resonance (EPR) of 7(Sb(2)F(11))(2) doped in
      10(Sb(2)F(11))(2) is in agreement with the triplet state arising from the weak
      coupling between the unpaired electrons residing in p(pi) orbitals in each of the
      rings. Variable-temperature susceptibility data for bulk samples of 7(A)(2) (A =
      SbF(6)(-), AsF(6)(-), Sb(2)F(11)(-)) are analyzed by employing both 1D chain and
      2D sheet magnetic models. These studies reveal significant intermolecular
      exchange approximating that of a 1D chain for the SbF(6)(-) salt with |J| = 32
      cm(-1). The exchange coupling is on the same order of magnitude as that for the
      AsF(6)(-) salt, although in this case it is likely that there are complex
      exchange pathways where no particular one is dominant. Intermolecular exchange in
      the Sb(2)F(11)(-) salt is an order of magnitude weaker. In solution, the EPR
      spectrum of 7(2+) shows a broad triplet resonance as well as a sharp resonance
      that is tentatively attributed to a rotomer of the 7(2+)/anion pair, which is
      likely the origin of the green species given on dissolution of the red 7(2+)
      salts in SO(2)/AsF(3)/MF(5). We account for the many similarities between O(2)
      and 7(2+), which are the only simple nonsterically hindered nonmetal diradicals
      to retain their paramagnetism in the solid state. 7(2+) is also the first
      isolable, essentially sulfur-based diradical as evidenced by calculated spin
      densities.

PMID- 20698502
TI  - Integration of a precolumn fluorogenic reaction, separation, and detection of
      reduced glutathione.
AB  - Reduced glutathione (GSH) has been determined by fluorescence detection after
      derivatization together with a variety of separations. The reactions between GSH
      and fluorescent reagents usually are carried out during the sample pretreatment
      and require minutes to hours for complete reactions. For continuous monitoring of
      GSH, it would be very convenient to have an integrated microdevice that could
      perform online precolumn derivatization, separation, and detection. Heretofore,
      thiol-specific fluorogenic reagents require fairly long reaction times,
      preventing effective online precolumn derivatization. We demonstrate here that
      the fluorogenic, thiol-specific reagent, ThioGlo-1, reacts rapidly enough for
      efficient precolumn derivatization. The second order rate constant for the
      reaction of GSH and reagent (pH 7.5, room temperature) is 2.1 x 10(4) M(-1)s(-1).
      The microchip integrates this precolumn derivatization, continuous flow gated
      sampling, separation, and detection on a single device. We have validated this
      device for monitoring GSH concentration continuously by studying the kinetics of
      glutathione reductase (EC 1.8.1.7), an enzyme that catalyzes the reduction of
      oxidized glutathione (GSSG) to GSH in the presence of beta-NADPH (beta
      nicotinamide adenine dinucleotide phosphate, reduced form) as a reducing
      cofactor. During the experiment, GSH being generated in the enzymatic reaction
      was labeled with ThioGlo-1 as it passed through a mixing channel on the
      microfluidic chip. Derivatization reaction products were introduced into the
      analysis channel every 10 s using flow gated injections of 0.1 s. Baseline
      separation of the internal standard, ThioGlo-1, and the fluorescently labeled GSH
      was successfully achieved within 4.5 s in a 9 mm separation channel. Relative
      standard deviations of the peak area, peak height, and full width at half-maximum
      (fwhm) for the internal standard were 2.5%, 2.0%, and 1.0%, respectively, with
      migration time reproducibility for the internal standard of less than 0.1% RSD in
      any experiment. The GSH concentration and mass detection limit were 4.2 nM and
      approximately 10(-18) mol, respectively. The Michaelis constants (K(m)) for GSSG
      and beta-NADPH were found to be 40 +/- 11 and 4.4 +/- 0.6 muM, respectively,
      comparable with those obtained from UV/vis spectrophotometric measurements. These
      results show that this system is capable of integrating derivatization,
      injection, separation, and detection for continuous GSH determinations.

PMID- 20698505
TI  - PEGylation of carboxylic acid-functionalized germanium nanowires.
AB  - Germanium (Ge) nanowires were produced in solution by supercritical fluid-liquid
      solid (SFLS) growth and then functionalized with carboxylic acid groups by in
      situ thermal thiolation with mercaptoundecanoic acid. Polyethylene glycol (PEG)
      was grafted to the carboxylic acid-terminated Ge nanowires using carbodiimide
      coupling chemistry. The nanowires were characterized using attenuated total
      reflectance Fourier transform infrared (ATR-FTIR) spectroscopy and transmission
      electron microscopy (TEM) to confirm the surface modification of the nanowires.
      Dispersions of PEGylated Ge nanowires in dimethylsulfoxide (DMSO) were stable for
      days. The PEGylated Ge nanowires were also dispersible in aqueous solution over a
      wide range of pH and ionic strength.

PMID- 20698506
TI  - A new model for quantifying the extent of interaction between soluble
      polyphenylene-vinylenes and single-walled carbon nanotubes in solvent
      dispersions.
AB  - The ability to disperse and, hence, manipulate single-walled carbon nanotubes is
      critical for their use in organic photovoltaic devices, either as a transparent
      electrode or as an electron acceptor material. We present data to quantify the
      physical interaction of single wall carbon nanotubes (SWCNTs) with two soluble
      phenylene vinylene conjugated polymers, poly[2'-methoxy-5-(2'-ethylhexyloxy)-1,4
      phenylenevinylene] and poly(2,5-di(hexyloxy)cyanoterephthalylidene). We provide
      static quenching constants, associated with polymer-SWCNT complexation, as a
      weight percent ratio of polymer to nanotubes for different solvent and polymer
      concentration conditions. Optimization of conditions for nanotube dispersion
      using a given polymer can now be predicted, and furthermore, we can describe a
      technique allowing for enhanced relative comparisons of polymer materials for
      nanotube dispersion.

PMID- 20698507
TI  - FRET between BODIPY azide dye clusters within PEG-based hydrogel: a handle to
      measure stimuli responsiveness.
AB  - The purpose of this paper is to investigate the dynamics of the fluorescence
      mechanism of boradiazaindacene (BODIPY) dye molecules, which are covalently bound
      to a polyethylene glycol based hydrogel structure with different concentrations,
      using a picosecond time-resolved spectroscopic technique. Since the hydrogel
      structure is capable of absorbing a large amount of water, without dissolving and
      without losing its shape, upon swelling, the distance between the BODIPY azide
      dyes is controllably changed; it is observed that the intensity weighted
      fluorescence lifetime for the highly concentrated donor dye molecules embedded in
      the hydrogel cluster network changes from 2.03 to 7.14 ns. Calculations based on
      our experimental results suggest that the fluorescence dynamics of the BODIPY
      azide dye molecules confined within the hydrogel network obeys the Forster
      resonance energy transfer (FRET) rather than self (or contact) quenching. If the
      hydrogel is dry, in which the distance between donors and acceptors is minimum,
      the energy transfer efficiency is found to be about 72%, and the distance between
      the two dye molecules is calculated to be 4.59 nm. Such a close placement causes
      a significant reduction in the fluorescence intensity due to a strong dipole
      dipole interaction of the dye molecules. As the separation increases upon
      hydrogel swelling, the FRET efficiency reduces to 2%, which corresponds to a
      separation of 10 nm between two BODIPY dyes and hence a considerable increase in
      the level of fluorescence intensity. For the dilute hydrogel samples, the
      distance between the dye molecules is larger than the critical Forster distance.
      Therefore, the energy transfer efficiency for this type of dilute samples is
      found to be much lower.

PMID- 20698508
TI  - Transformation relationships among monomers, micelles, metastable solid, and
      stable solid in aqueous cetylpyridinium chloride solution.
AB  - Kinetic studies on metamorphoses among monomer, micelle, metastable solid, and
      stable solid during the Krafft transition of cetylpyridinium chloride (CPC) in
      the aqueous solution were carried out. The Krafft transition accompanied a
      decrease of the electric conductance with a large increment of the dielectric
      permittivity Delta epsilon, which vanished after finishing the transition. The
      observing duration of large Delta epsilon in transforming to the metastable solid
      was much shorter than the duration in transforming to the stable solid. From the
      observing duration of Delta epsilon, a formation boundary between the metastable
      and the stable solids was determined as a function of the temperature and the CPC
      concentration. It was found from the boundary that the metastable solid forms in
      the micelle solution. A change in the electric conductivity kappa of metastable
      solid suspensions during metastable-stable transformation suggests the solid
      dissolution-limited metamorphosis of metastable solid into the stable solid in
      the solution. Arrhenius plots of the metastable-stable transformation durations
      obtained from the time courses of kappa changes gave the high activation energy
      of 290 kJ/mol for the metastable solid dissolution-limited metastable-stable
      transition.

PMID- 20698509
TI  - Interaction of daunomycin with acetylated chromatin.
AB  - Anthracyclines are powerful chemotherapeutic agents for the treatment of many
      cancers. In many instances, they are currently used in combination with histone
      deacetylase inhibitors in order to enhance their efficiency. Not surprisingly and
      as part of their mode of action, these drugs interfere with gene expression, a
      process that has long been known to be mediated by histone acetylation. In this
      paper, we use analytical ultracentrifuge analysis, equilibrium dialysis, and
      circular dichroism to characterize the role of histone acetylation on the binding
      of antharcyclines to chromatin. We show that histone acetylation enhances the
      daunomycin-induced DNA dissociation from nucleosomes and decreases the extent of
      aggregation that results from the interaction in a way that is modulated by the
      presence or absence of linker histones. Histone acetylation increases the binding
      affinity of daunomycin by chromatin. Furthermore, the binding of anthracycline to
      acetylated chromatin sheds additional light into the conformational chromatin
      alterations resulting from core histone acetylation.

PMID- 20698510
TI  - Direct synthesis of 6-arylpurines by reaction of 6-chloropurines with activated
      aromatics.
AB  - Highly functionalized C6-aryl-substituted purine analogues were synthesized
      through direct arylation of 6-chloropurine with aromatics promoted by anhydrous
      AlCl(3) in a single step. The reactions, which were conducted using a 3-fold
      excess of AlCl(3) in refluxing 1,2-dichloroethane, gave moderate to excellent
      product yields in 0.5 h. This work is complementary to the classical coupling
      reactions for the synthesis of C6-aryl-substituted purine analogues.

PMID- 20698511
TI  - Study on intercalations between double-stranded DNA and pyrene by single-molecule
      force spectroscopy: toward the detection of mismatch in DNA.
AB  - Intercalation interactions between planar aromatic molecules and double-stranded
      DNA (dsDNA) relate to not only the structure of the guest molecules but also the
      structure of the dsDNA. In this letter, we have comparatively studied the
      intercalation between pyrene and fully matched or mismatched dsDNA using single
      molecule force spectroscopy (SMFS). The significant difference in rupture forces,
      upon pyrene unbinding from 25-mer dsDNA with or without mismatches, is observed
      at the single-molecule level, indicating the influence of mismatches on the
      interaction between pyrene and dsDNA. In the analysis of the dynamic force
      spectra, two transition barriers are revealed for pyrene unbinding from matched
      sites in dsDNA and for pyrene unbinding from mismatched sites as well. These
      results suggest that SMFS is a useful single-molecule method for the detection of
      mismatches in dsDNA by the intercalation of pyrene.

PMID- 20698512
TI  - Direct observations of three nucleation/growth processes of charge-stabilized
      dispersion polymerizations with varying water/methanol ratios.
AB  - This article presents observations of three polymerization modes of a self
      developed cation-charge-stabilized styrene/water/methanol dispersion
      polymerization system: (1) a water/methanol (20/80) system, corresponding to a
      typical dispersion polymerization mode where the particle nucleation occurred in
      the solution phase and growth in the particle phase; (2) a pure CH(3)OH system,
      including a first nucleation in the solution phase with growth by absorption of
      the small particles and polymers formed in this phase, and a secondary nucleation
      with growth in the particle phase, when high molecular weight copolymers appeared
      in the solution phase; and (3) a water/methanol (5/95) system, similar to the
      conventional dispersion polymerization mode during the first 90 min, with
      subsequent epitaxial growth. Interestingly, the metastable state of the
      nucleation stage, including minuscule 6-nm particles, their aggregates, and the
      aggregating process, was first observed experimentally. By quantitatively
      following the relationship of the deposited molecular weight and the
      nucleation/growth process in the three systems, it was proposed that the
      molecular weight of the deposited polymer had to reach a specific high value
      before they could absorb or capture monomer to form smooth/spherical nuclei or
      particles.

PMID- 20698513
TI  - Photoreactions and molecular dynamics of radical pairs in a reversed micelle
      studied by time-resolved measurements of EPR and magnetic field effect.
AB  - Photoreaction of N,N,N',N'-tetramethyl-1,4-phenylenediamine (TMPD) in an aerosol
      OT (AOT) reversed micelle (RM) is studied by time-resolved EPR (tr-EPR) and the
      transient absorption detected magnetic field effect (MFE). Tr-EPR and transient
      absorption spectra indicate electron transfer from a highly excited triplet state
      of TMPD to the AOT headgroup regardless of W = [H(2)O]/[AOT] values from 0 to 40.
      Noticeable MFEs on the yield of TMPD cation radical (TMPD(+)) are observed at W >
      0 and maximized at W ~ 10. The dynamics of TMPD(+) in the bound water region of
      the RM has been precisely analyzed by theoretical analysis of time-resolved
      magnetically affected reaction yield (MARY) spectra. The simulation of the MARY
      spectra indicates that two kinds of radical pairs exist, both of which are
      composed of an AOT alkyl radical and TMPD(+). One system has TMPD(+) strongly
      bound to the anionic interface, where the radical pair shows very slow relaxation
      and recombination. Another system has TMPD(+) diffusing in the bound water, which
      shows a smaller diffusion coefficient than that in bulk water by 1 order of
      magnitude. In the larger water pool (W > 15), the spin correlated radical pair of
      the hydrated electron and TMPD(+) generated by photoionization is observed by tr
      EPR. The ionization reaction is followed by electron attachment to the AOT
      headgroup and generation of the sulfite radical. However, these radical pairs are
      not thought to contribute significantly to the observed MFEs. Spin multiplicities
      of the precursor state and recombination products have been discussed from the
      different sign of J values for the radical pairs at larger W.

PMID- 20698514
TI  - Molecular assemblies of 4-(hexadecyloxy)-n-(pyridinylmethylene)anilines at the
      air-water interface and Cu(II)-promoted vesicle formation via metal coordination.
AB  - The molecular assemblies of 4-(hexadecyloxy)-N-(pyridinylmethylene)anilines (HPA)
      at the air-water interface on pure water and aqueous Cu(II) subphases have been
      investigated using in situ infrared reflection absorption spectroscopy (IRRAS).
      The Schiff base units were oriented with their long axes almost perpendicular to
      the water surface, and both imine and pyridinyl nitrogen atoms of the Schiff base
      units were coordinated to Cu(II) ions together with their geometrical
      conversions. The alkyl chains in the monolayers were quantitatively determined on
      the assumption that the HPA monolayers at the air-water interface were composed
      of sublayers of alkyl chains and Schiff base units, and the chain orientation
      angle on pure water was 30 +/- 2 degrees and increased to 37 +/- 2 degrees on the
      aqueous Cu(II) subphase. The HPA amphiphiles could not be dispersed in pure water
      but could self-organize into vesicles with metal-coordinated headgroups and
      interdigitated-packed alkyl chains in the presence of Cu(II) ions in aqueous
      solution. Transmission electron microscopy (TEM), differential scanning
      calorimetry (DSC), UV-vis spectroscopy, and small-angle X-ray diffraction (XRD)
      were used to investigate the aggregate structures and specific properties of the
      coordinated vesicles.

PMID- 20698515
TI  - Stereospecific substitution of allylic alcohols to give optically active primary
      allylic amines: unique reactivity of a (P,alkene)Ir complex modulated by iodide.
AB  - A stereospecific allylic amination of unactivated secondary (secondary)-allylic
      alcohols is reported. The primary (primary)-allylic amine can be isolated
      directly or protected in situ. Spectroscopic studies have shed light on the
      structure of the catalytically active Ir x (P,olefin)2I complex.

PMID- 20698516
TI  - Characterization of acoustic cavitation bubbles in different sound fields.
AB  - Various fundamental properties of acoustic cavitation bubbles have been
      investigated in single- and dual-frequency sound fields. It was found that the
      relative extent of bubble coalescence in the dual-frequency field correlated
      strongly with the synergistic enhancement of the sonochemical reaction rates.
      Both the relative extent of coalescence and the sonochemical synergy observed
      were enhanced through the addition of coalescence-inhibiting solutes. This was
      attributed to greater nucleation in the dual-frequency mode compared with the
      single-frequency modes, producing a very localized and high-density bubble field.
      The acoustic bubble size, compared with that measured at 355 kHz alone, was found
      to increase upon the application of synchronous 20 kHz pulses but was reduced
      dramatically when the low frequency was applied as a continuous wave. This trend
      is consistent with previous reports indicating that the bubble density and
      cavitation activity are relatively higher in the pulsed system and that the
      continuous wave application exerts a strong cancellation effect. The changes in
      bubble density and coalescence rates are proposed to govern the acoustic bubble
      size. The bubble lifetime was found to be longer in the dual-frequency field
      (>0.30 ms; >6 low-frequency oscillations, >100 high-frequency oscillations)
      compared with both single-frequency fields (0.26 ms and 5 oscillations for the
      low frequency; 0.22 ms and 75 oscillations for the high frequency). The
      confluence of a longer bubble lifetime and more asymmetric collapse conditions,
      the latter inferred from a more pronounced sodium atom emission in the
      sonoluminescence spectrum, resulted in a lower bubble collapse temperature
      measured in the dual-frequency system.

PMID- 20698517
TI  - Interfacial properties of water/CO2: a comprehensive description through a
      Gradient Theory-SAFT-VR Mie approach.
AB  - The Gradient Theory of fluid interfaces is for the first time combined with the
      SAFT-VR Mie EOS to model the interfacial properties of the water/CO(2) mixture.
      As a preliminary test of the performance of the coupling between both theories,
      liquid-vapor interfacial properties of pure water have been determined. The
      complex temperature dependence of the surface tension of water can be accurately
      reproduced, and the interfacial thickness is in good agreement with experimental
      data and simulation results. The water/CO(2) mixture presents several types of
      interfaces as the liquid water may be in contact with gaseous, liquid, or
      supercritical CO(2). Here, the interfacial tension of the water/CO(2) mixture is
      modeled accurately by the gradient theory with a unique value of the crossed
      influence parameter over a broad range of thermodynamic conditions. The
      interfacial density profiles show a systematic adsorption of CO(2) in the
      interface. Moreover, when approaching the saturation pressure of CO(2), a
      prewetting transition is highlighted. The adsorption isotherm of CO(2) is
      computed as well in the case of a gas/liquid interface and compared with
      experimental data. The good agreement obtained is an indirect proof of the
      consistency of interfacial density profiles computed with the gradient theory for
      this mixture and confirms that the gradient theory is suitable and reliable to
      describe the microstructure of complex fluid interfaces.

PMID- 20698518
TI  - Free energy landscape of the retinol/serum retinol binding protein complex: a
      biological host-guest system.
AB  - Small molecule host-guest complexes have traditionally provided model systems for
      biological ligand recognition. Nonetheless, direct extrapolation of these results
      is precluded by the comparative simplicity of these supramolecular assemblies. If
      energetic behavior analogous to small molecule host-guest chemistry exists, it is
      unclear how this would manifest for protein-small molecule interactions. To
      answer this question, we employ the retinol/serum retinol binding protein (sRBP)
      system as an analogue of a classical host-guest complex. Using a combination of
      molecular dynamics simulations and free energy methods, we decompose the
      potential of mean force for retinol unbinding from the sRBP into constituent
      interactions. Our calculations reveal an unexpected mechanism of host-guest
      complexation. Desolvation is sufficient to drive formation of an intermediate
      binding state; however, a combination of electrostatic and van der Waals
      interactions pull the intermediate into a stable configuration. Association is
      accompanied by a change in the conformational flexibility of the portal domains
      of sRBP and subsequent "stiffening" of the holo sRBP, reflecting an "order
      disorder" transition in the protein.

PMID- 20698519
TI  - The protonation state of Glu181 in rhodopsin revisited: interpretation of
      experimental data on the basis of QM/MM calculations.
AB  - The structure and spectroscopy of rhodopsin have been intensely studied in the
      past decade both experimentally and theoretically; however, important issues
      still remain unresolved. Of central interest is the protonation state of Glu181,
      where controversial and contradictory experimental evidence has appeared. While
      FTIR measurements indicate this residue to be unprotonated, preresonance Raman
      and UV-vis spectra have been interpreted in favor of a protonated Glu181.
      Previous computational approaches were not able to resolve this issue, providing
      contradicting data as well. Here, we perform hybrid QM/MM calculations using DFT
      methods for the electronic ground state, MRCI methods for the electronically
      excited states, and a polarization model for the MM part in order to investigate
      this issue systematically. We constructed various active-site models for
      protonated as well as unprotonated Glu181, which were evaluated by computing NMR,
      IR, Raman, and UV-vis spectroscopic data. The resulting differences in the UV-vis
      and Raman spectra between protonated and unprotonated models are very subtle,
      which has two major consequences. First, the common interpretation of prior Raman
      and UV-vis experiments in favor of a neutral Glu181 appears questionable, as it
      is based on the assumption that a charge at the Glu181 location would have a
      sizable impact. Second, also theoretical results should be interpreted with care.
      Spectroscopic differences between the structural models must be related to
      modeling uncertainties and intrinsic methodological errors. Despite a detailed
      comparison of various rhodopsins and mutants and consistently favorite results
      with charged Glu181 models, we find merely weak evidence from UV-vis and Raman
      calculations. On the contrary, difference FTIR and NMR chemical shift
      measurements on Rh mutants are indicative of the protonation state of Glu181.
      Supported by our results, they provide strong and independent evidence for a
      charged Glu181.

PMID- 20698520
TI  - Controlling the adsorption kinetics via nanostructuring: Pd nanoparticles on TiO2
      nanotubes.
AB  - Activity and selectivity of supported catalysts critically depend on transport
      and adsorption properties. Combining self-organized porous oxide films with
      different metal deposition techniques, we have prepared novel Pd/TiO(2) catalysts
      with a new level of structural control. It is shown that these systems make it
      possible to tune adsorption kinetics via their nanostructure. Self-organized
      TiO(2) nanotubular arrays (TiNTs) prepared by electrochemical methods are used as
      a support, on which Pd particles are deposited. Whereas physical vapor deposition
      (PVD) in ultrahigh vacuum (UHV) allows us to selectively grow Pd particles at the
      tube orifice, Pd/TiNT systems with homogeneously distributed Pd aggregates inside
      the tubes are available by particle precipitation (PP) from solution. Both
      methods also provide control over particle size and loading. Using in-situ
      infrared reflection absorption spectroscopy (IRAS) and molecular beam (MB)
      methods, we illustrate the relation between the nanostructure of the Pd/TiNT
      systems and their adsorption kinetics. Control over the metal nanoparticle
      distribution in the nanotubes leads to drastic differences in adsorption
      probability and saturation behavior. These differences are rationalized based on
      differences in surface and gas phase transport resulting from their
      nanostructure. The results suggest that using carefully designed metal/TiNT
      systems it may be possible to tailor transport processes in catalytically active
      materials.

PMID- 20698521
TI  - Stable biomimetic superhydrophobic surfaces fabricated by polymer replication
      method from hierarchically structured surfaces of Al templates.
AB  - We have developed a simple, efficient, and highly reproducible method to
      fabricate the large-area biomimetic superhydrophobic polymer surfaces having
      hierarchical structures of micrometer-sized irregular steps and nanometer-sized
      fibrils. Commercial Al plates (99.0%) were etched using Beck's dislocation
      etchant (mixture of HCl and HF) for different time periods in order to alter the
      structure of the etched Al surfaces from micrometer-sized to highly rough
      nanometer-sized irregular steps. These hierarchical structures could be easily
      replicated onto the surface of various thermoplastic polymer plates from the
      etched Al templates by applying heat and pressure; many polymer replicas without
      any significant deviations from each other could be duplicated from the same
      etched Al master templates. All of thermoplastic polymer replicas having
      hierarchical structures exhibited superhydrophobic properties with water contact
      angles of larger than 150 degrees. Especially, the surfaces of the high-density
      polyethylene (HDPE) replicas having nanometer-sized curled strands exhibited
      superhydrophobicity with a static water contact angle of approximately 160
      degrees and a sliding angle of less than 2 degrees. These superhydrophobic HDPE
      replicas having nanometer-sized curled strands showed excellent stability after
      being exposed to various organic solvents and aqueous solutions of various pH.

PMID- 20698522
TI  - Redox mechanism of glycosidic bond hydrolysis catalyzed by 6-phospho-alpha
      glucosidase: a DFT study.
AB  - Glycosidic bonds are remarkably resistant to cleavage by chemical hydrolysis.
      Glycoside hydrolases catalyze their selective hydrolysis in oligosaccharides,
      polysaccharides, and glycoconjugates by following nonredox catalytic pathways or
      a net redox-neutral catalytic pathway using NAD(+) and divalent metal ions as
      cofactors. GlvA (6-phospho-alpha-glucosidase) is a glycosidase belonging to
      family GH4 and follows a regioselective redox-neutral mechanism of glycosidic
      bond hydrolysis that favors alpha- over beta-glycosides. Its proposed catalytic
      mechanism can be divided into two half-reactions: the first one activates the
      glucopyranose ring by successively forming intermediates that are oxidized at the
      3-, 2-, and 1-positions of the ring, which ultimately facilitate the heterolytic
      deglycosylation. The second half-reaction is essentially the reverse of the first
      half-reaction, beginning with the pyranose ring hydroxylation at the anomeric
      carbon, and it is followed by 3-reduction and regeneration of the active forms of
      the catalytic site and its cofactors. We investigated the NAD(+)-dependent redox
      mechanism of glycosidic bond hydrolysis as catalyzed by GlvA through the combined
      application of density functional theory and a self-consistent reaction field to
      a large active-site model obtained from the crystallographic structure of the
      enzyme, then we applied natural bond orbital and second-order perturbation
      analyses to monitor the electron flow and change in oxidation state on each
      atomic center along the reaction coordinate to rationalize the energetics and
      regioselectivity of this catalytic mechanism. We find that in GlvA, the redox
      catalytic mechanism of hydrolysis is driven by the gradual strengthening of the
      axial endo-anomeric component within the hexose ring along the reaction
      coordinate to facilitate the heterolytic dissociation of the axial C1-O bond. In
      addition, the combined influence of specific components of the generalized
      anomeric effect fully explains the regioselectivity observed in the catalytic
      activity of GlvA.

PMID- 20698523
TI  - Semiconducting nanowires from hairpin-shaped self-assembling sexithiophenes.
AB  - Conjugated organic molecules can be designed to self-assemble from solution into
      nanostructures for functions such as charge transport, light emission, or light
      harvesting. We report here the design and synthesis of a novel hairpin-shaped
      self-assembling molecule containing electronically active sexithiophene moieties.
      In several nonpolar organic solvents, such as toluene or chlorocyclohexane, this
      compound was found to form organogels composed of nanofibers with uniform
      diameters of 3.0 (+/-0.3) nm. NMR analysis and spectroscopic measurements
      revealed that the self-assembly is driven by pi-pi interactions of the
      sexithiophene moieties and hydrogen bonding among the amide groups at the head of
      the hairpin. Field effect transistors built with this molecule revealed p-type
      semiconducting behavior and higher hole mobilities when films were cast from
      solvents that promote self-assembly. We propose that hydrogen bonding and pi-pi
      stacking act synergistically to create ordered stacking of sexithiophene
      moieties, thus providing an efficient pathway for charge carriers within the
      nanowires. The nanostructures formed exhibit unusually broad absorbance in their
      UV-vis spectrum, which we attribute to the coexistence of both H and J aggregates
      from face-to-face pi-pi stacking of sexithiophene moieties and hierarchical
      bundling of the nanowires. The large absorption range associated with self
      assembly of the hairpin molecules makes them potentially useful in light
      harvesting for energy applications.

PMID- 20698524
TI  - Synthesis of cis-3-acyl-4-alkenylpyrrolidines via gold(I)-catalyzed
      cycloisomerization reaction of (Z)-8-aryl-5-tosyl-5-azaoct-2-en-7-yn-1-ols.
AB  - (Z)-8-Aryl-5-tosyl-5-azaoct-2-en-7-yn-1-ols were cycloisomerized to the
      corresponding cis-3-acyl-4-alkenylpyrrolidines when treated with a catalytic
      amount of Ph(3)PAuCl/AgOTf in CH(2)Cl(2). The reaction proceeded via attack of
      the hydroxyl group onto the gold-activated alkynes followed by [3,3]-sigmatropic
      rearrangement to generate cis-3-acyl-4-alkenylpyrrolidines in good yields. This
      transformation can be applied to the synthesis of cis- and trans-3-acyl-4
      alkenylcyclopentanes from (Z)- and (E)-8-aryloct-2-en-7-yn-1-ols, respectively.

PMID- 20698525
TI  - Use and environmental occurrence of antibiotics in freestall dairy farms with
      manured forage fields.
AB  - Environmental releases of antibiotics from concentrated animal feeding operations
      (CAFOs) are of increasing regulatory concern. This study investigates the use and
      occurrence of antibiotics in dairy CAFOs and their potential transport into first
      encountered groundwater. On two dairies we conducted four seasonal sampling
      campaigns, each across 13 animal production and waste management systems and
      associated environmental pathways: application to animals, excretion to surfaces,
      manure collection systems, soils, and shallow groundwater. Concentrations of
      antibiotics were determined using on line solid phase extraction (OLSPE) and
      liquid chromatography-tandem mass spectrometry (LC/MS/MS) with electrospray
      ionization (ESI) for water samples, and accelerated solvent extraction (ASE)
      LC/MS/MS with ESI for solid samples. A variety of antibiotics were applied at
      both farms leading to antibiotics excretion of several hundred grams per farm per
      day. Sulfonamides, tetracyclines, and their epimers/isomers, and lincomycin were
      most frequently detected. Yet, despite decades of use, antibiotic occurrence
      appeared constrained to within farm boundaries. The most frequent antibiotic
      detections were associated with lagoons, hospital pens, and calf hutches. When
      detected below ground, tetracyclines were mainly found in soils, whereas
      sulfonamides were found in shallow groundwater reflecting key differences in
      their physicochemical properties. In manure lagoons, 10 compounds were detected
      including tetracyclines and trimethoprim. Of these 10, sulfadimethoxine,
      sulfamethazine, and lincomycin were found in shallow groundwater directly
      downgradient from the lagoons. Antibiotics were sporadically detected in field
      surface samples on fields with manure applications, but not in underlying sandy
      soils. Sulfadimethoxine and sulfamethazine were detected in shallow groundwater
      near field flood irrigation gates, but at highly attenuated levels.

PMID- 20698527
TI  - ONIOM study on a missing piece in our understanding of heme chemistry: bacterial
      tryptophan 2,3-dioxygenase with dual oxidants.
AB  - Unique heme-containing tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3
      dioxygenase (IDO) catalyze oxidative cleavage of the pyrrole ring of L-tryptophan
      (Trp). Although these two heme dioxygenases were discovered more than 40 years
      ago, their reaction mechanisms were still poorly understood. Encouraged by recent
      X-ray crystal structures, new mechanistic pathways were proposed. We performed
      ONIOM(B3LYP:Amber) calculations with explicit consideration of the protein
      environment to study various possible reaction mechanisms for bacterial TDO. The
      ONIOM calculations do not support the proposed mechanisms (via either formation
      of the dioxetane intermediate or Criegee-type rearrangement); a mechanism that is
      exceptional in the hemes emerges. It starts with (1) direct radical addition of a
      ferric-superoxide intermediate with C2 of the indole of Trp, followed by (2) ring
      closure via homolytic O-O cleavage to give epoxide and ferryl-oxo (Cpd II)
      intermediates, (3) acid-catalyzed regiospecific ring-opening of the epoxide, (4)
      oxo-attack, and (5) finally C-C bond cleavage concerted with back proton
      transfer. The involvement of dual oxidants, ferric-superoxide and ferryl-oxo (Cpd
      II) intermediates, is proposed to be responsible for the dioxygenase reactivity
      in bacterial TDO. In particular, the not-well-recognized ferric-superoxide
      porphyrin intermediate is found to be capable of reacting with pi-systems via
      direct radical addition, an uncommon dioxygen activation in the hemes. The
      comparison between Xanthomonas campestris TDO and some heme as well non-heme
      oxygenases is also discussed.

PMID- 20698526
TI  - Directly Pd(II)-bridged porphyrin belts with remarkable curvatures.
AB  - A beta,beta'-doubly 2,6-pyridylene-bridged porphyrin dimer and trimer were
      prepared by Suzuki-Miyaura coupling reactions and confirmed to have largely bent
      structures. These oligoporphyrins were readily metalated via meso-C-H bond
      activation with the assistance of the pyridyl nitrogen atoms to produce the
      corresponding Pd(II) complexes, which display even larger bent structures and
      larger TPA values at 800 nm.

PMID- 20698528
TI  - Role of aromatic rings in the molecular recognition of aminoglycoside
      antibiotics: implications for drug design.
AB  - Aminoglycoside antibiotics participate in a large variety of binding processes
      involving both RNA and proteins. The description, in recent years, of several
      clinically relevant aminoglycoside/receptor complexes has greatly stimulated the
      structural-based design of new bioactive derivatives. Unfortunately, design
      efforts have frequently met with limited success, reflecting our incomplete
      understanding of the molecular determinants for the antibiotic recognition.
      Intriguingly, aromatic rings of the protein/RNA receptors seem to be key actors
      in this process. Indeed, close inspection of the structural information available
      reveals that they are frequently involved in CH/pi stacking interactions with
      sugar/aminocyclitol rings of the antibiotic. While the interaction between
      neutral carbohydrates and aromatic rings has been studied in detail during past
      decade, little is known about these contacts when they involve densely charged
      glycosides. Herein we report a detailed experimental and theoretical analysis of
      the role played by CH/pi stacking interactions in the molecular recognition of
      aminoglycosides. Our study aims to determine the influence that the antibiotic
      polycationic character has on the stability, preferred geometry, and dynamics of
      these particular contacts. With this purpose, different aminoglycoside/aromatic
      complexes have been selected as model systems. They varied from simple
      bimolecular interactions to the more stable intramolecular CH/pi contacts present
      in designed derivatives. The obtained results highlight the key role played by
      electrostatic forces and the desolvation of charged groups in the molecular
      recognition of polycationic glycosides and have clear implications for the design
      of improved antibiotics.

PMID- 20698529
TI  - Gold-catalyzed annulation/fragmentation: formation of free gold carbenes by retro
      cyclopropanation.
AB  - The gold(I)-catalyzed cyclization of 1-(prop-2-yn-1-yl)-2-alkenylbenzenes
      substituted at the benzylic position with OR groups gives 1,3-disubstituted
      naphthalenes with concomitant fragmentation of the alkene. One of these
      annulations proceeds by a retro-cyclopropanation that leads to free gold(I)
      carbenes.

PMID- 20698530
TI  - Complexation of cyclohexanocucurbit[6]uril with cadmium ions: X-ray
      crystallographic and electrochemical study.
AB  - Complexation of cyclohexanocucurbit[6]uril (Q*[6]), a water-soluble
      cucurbit[n]uril derivative, with Cd(2+) ions has been studied by means of cyclic
      voltammetry and differential pulse voltammetry. The electrochemical experimental
      data prove the formation of a highly stable 1:6 Q*[6]/Cd(2+) complex. We also
      obtained the single-crystal X-ray structure of a cadmium ion complex with Q*[6],
      in which each portal of Q*[6] chelates three cadmium ions. The present study
      suggests the potential utility of Q*[6] as an effective cadmium ion chelator and
      extractant.

PMID- 20698531
TI  - Direct imaging of intermolecular bonds in scanning tunneling microscopy.
AB  - Local, noncovalent intermolecular interactions in organic monolayers have been
      directly imaged using scanning tunneling hydrogen microscopy (STHM).
      Unprecedented spatial resolution directly reveals the relation between the
      intermolecular interactions, the molecular chemical structure, and the ordering
      in the film.

PMID- 20698532
TI  - Combining NMR and EPR methods for homodimer protein structure determination.
AB  - There is a general need to develop more powerful and more robust methods for
      structural characterization of homodimers, homo-oligomers, and multiprotein
      complexes using solution-state NMR methods. In recent years, there has been
      increasing emphasis on integrating distinct and complementary methodologies for
      structure determination of multiprotein complexes. One approach not yet widely
      used is to obtain intermediate and long-range distance constraints from
      paramagnetic relaxation enhancements (PRE) and electron paramagnetic resonance
      (EPR)-based techniques such as double electron electron resonance (DEER), which,
      when used together, can provide supplemental distance constraints spanning to 10
      70 A. In this Communication, we describe integration of PRE and DEER data with
      conventional solution-state nuclear magnetic resonance (NMR) methods for
      structure determination of Dsy0195, a homodimer (62 amino acids per monomer) from
      Desulfitobacterium hafniense. Our results indicate that combination of
      conventional NMR restraints with only one or a few DEER distance constraints and
      a small number of PRE constraints is sufficient for the automatic NMR-based
      structure determination program CYANA to build a network of interchain nuclear
      Overhauser effect constraints that can be used to accurately define both the
      homodimer interface and the global homodimer structure. The use of DEER distances
      as a source of supplemental constraints as described here has virtually no upper
      molecular weight limit, and utilization of the PRE constraints is limited only by
      the ability to make accurate assignments of the protein amide proton and nitrogen
      chemical shifts.

PMID- 20698533
TI  - Mechanical nanosprings: induced coiling and uncoiling of ultrathin Au nanowires.
AB  - We report the controllable coiling of colloidal gold nanowires induced by the
      contraction of their polymer shells. The mechanical energy stored in this process
      can be released upon removal or swelling of the polymer shells.

PMID- 20698534
TI  - Sc2(mu2-O) trapped in a fullerene cage: the isolation and structural
      characterization of Sc2(mu2-O)@C(s)6-C82 and the relevance of the thermal and
      entropic effects in fullerene isomer selection.
AB  - The new endohedral fullerene, Sc(2)(mu(2)-O)@C(s)(6)-C(82), has been isolated
      from the carbon soot obtained by electric arc generation of fullerenes utilizing
      graphite rods doped with 90% Sc(2)O(3) and 10% Cu (w/w). Sc(2)(mu(2)-O)@C(s)(6)
      C(82) has been characterized by single crystal X-ray diffraction, mass
      spectrometry, and UV/vis spectroscopy. Computational studies have shown that,
      among the nine isomers that follow the isolated pentagon rule (IPR) for C(82),
      cage 6 with C(s) symmetry is the most favorable to encapsulate the cluster at T >
      1200 K. Sc(2)(mu(2)-O)@C(s)(6)-C(82) is the first example in which the relevance
      of the thermal and entropic contributions to the stability of the fullerene
      isomer has been clearly confirmed through the characterization of the X-ray
      crystal structure.

PMID- 20698535
TI  - Quantitative catalyst-substrate association relationships between metathesis
      molybdenum or ruthenium carbene complexes and their substrates.
AB  - Herein we present the long-sought quantitative catalyst-substrate association
      relationships based on experimentally measured quantitative association
      preferences of diverse metathesis Mo and Ru catalysts (Mo-1, Schrock Mo; Mo-2,
      Schrock-Hoveyda Mo; Ru-1, Grubbs first generation Ru; Ru-2, Grubbs second
      generation Ru; Ru-3:, Grubbs-Hoveyda first generation Ru; and Ru-4, Grubbs
      Hoveyda second generation Ru) to their substrates (alkenes, alkynes and allenes),
      determined directly by a general method based on FRET principle. The determined
      substrate preferences are proved to be dependent on the molecular identity of the
      catalyst, exhibiting the preference order of alkyne > alkene > allene for Mo-1
      and Mo-2, allene > alkene > alkyne for Ru-1 and Ru-3, and alkyne > allene >
      alkene for Ru-2 and Ru-4. The results enable us to probe metathesis mechanisms by
      answering issues in metathesis reactions including the controversial reaction
      initiation in enyne or allenyne metathesis.

PMID- 20698536
TI  - Room temperature palladium-catalyzed decarboxylative ortho-acylation of
      acetanilides with alpha-oxocarboxylic acids.
AB  - A novel Pd-catalyzed decarboxylative ortho-acylation of acetanilides with alpha
      oxocarboxylic acids is realized at room temperature. This reaction provides
      efficient access to o-acyl acetanilides under mild conditions.

PMID- 20698537
TI  - Effect of carrot (Daucus carota) microstructure on carotene bioaccessibilty in
      the upper gastrointestinal tract. 1. In vitro simulations of carrot digestion.
AB  - Studies investigating carotene bioaccessibility (release from the food matrix to
      a solubilized form) directly from plant material during the process of digestion
      are scarce, mainly due to the difficulties associated with obtaining such
      material. Therefore, this paper examines the relationship between tissue
      microstructure and carotene bioaccessibility using an in vitro digestion model.
      Dietary oil provides a pool for the initial solubilization. Therefore, carotene
      partitioning into an emulsified oil phase was assessed using raw carrot tissue
      and carrot tissue subjected to various degrees of heating and particle size
      reduction and, in all cases, was found to be greatly reduced compared with juiced
      carrot. Carotene bioaccessibility was found to be greater from raw tissues than
      heated tissues of the same size. This is because heating increases the propensity
      for intact cells to separate, effectively encapsulating the carotene. Although
      the gross structure of the tissues was found to be relatively unaffected by in
      vitro digestion, at the cellular level some cell-wall swelling and cell death
      were observed, particularly close to the surfaces of the tissue. This study
      suggests that cell-wall rupture prior to digestion is an absolute requirement for
      carotene bioaccessibility in the upper intestine and that heating does not
      enhance carotene release from intact cells.

PMID- 20698538
TI  - Spin and orbital magnetic moment anisotropies of monodispersed
      bis(phthalocyaninato)terbium on a copper surface.
AB  - The magnetic properties of isolated TbPc(2) molecules supported on a Cu(100)
      surface are investigated by X-ray magnetic circular dichroism at 8 K in magnetic
      fields up to 5 T. The crystal field and magnetic properties of single molecules
      are found to be robust upon adsorption on a metal substrate. The Tb magnetic
      moment has Ising-like magnetization; XMCD spectra combined with multiplet
      calculations show that the saturation orbital and spin magnetic moment values
      reach 3 and 6 mu(B), respectively.

PMID- 20698539
TI  - Hispidulin potently inhibits human glioblastoma multiforme cells through
      activation of AMP-activated protein kinase (AMPK).
AB  - Glioblastoma multiforme (GBM) is the most common and lethal type of primary brain
      tumor. Despite recent therapeutic advances in other cancers, the treatment of GBM
      remains ineffective and essentially palliative. The current focus lies in the
      finding of components that activate the AMP-activated protein kinase (AMPK), one
      key enzyme thought to be activated during the caloric restriction (CR). In the
      present study, we found that treatment of hispidulin, a flavone isolated from
      Saussurea involucrate Kar. et Kir., resulted in dose-dependent inhibition of GBM
      cellular proliferation. Interestingly, we show that hispidulin activated AMPK in
      GBM cells. The activation of AMPK suppressed downstream substrates, such as the
      mammalian target of rapamycin (mTOR) and eukaryotic initiation factor 4E-binding
      protein-1 (4E-BP1), and resulted in a general decrease in mRNA translation.
      Moreover, hispidulin-activated AMPK decreases the activity and/or expression of
      lipogenic enzymes, such as fatty acid synthase (FASN) and acetyl-CoA carboxylase
      (ACC). Furthermore, hispidulin blocked the progression of the cell cycle at the
      G1 phase and induced apoptosis by inducing p53 expression and further
      upregulating p21 expression in GBM cells. On the basis of these results, we
      demonstrated that hispidulin has the potential to be a chemopreventive and
      therapeutic agent against human GBM.

PMID- 20698540
TI  - Isolation and identification of polymethoxyflavones from the hybrid Citrus,
      hallabong.
AB  - Seven polymethoxyflavones (PMFs) were isolated from the dried peels of hallabong,
      the hybrid Citrus , by a repeated column chromatography. The structures of PMFs
      were identified as 5,6,7,3',4'-pentamethoxyflavone (1), 6,7,8,3',4'
      pentamethoxyflavone (2), 3-hydroxy-5,6,7,4'-tetramethoxyflavone (3),
      5,6,7,8,3',4'-hexamethoxyflavone (4), 3,6,7,4'-tetramethoxyflavone (5),
      3,5,6,7,8,3',4'-heptamethoxyflavone (6), and 5,6,7,8,4'-pentamethoxyflavone (7)
      using 1H and 13C NMR in combination with mass spectrometry. Among these
      compounds, 5 was isolated for the first time from nature. The content of PMFs 1-7
      in hallabong was determined by HPLC-UV. The major PMFs of hallabong are 5 in the
      dried peels (15.4 mg/g) and 7 in the dried leaves (12.2 mg/g).

PMID- 20698541
TI  - Synthesis of tetrasubstituted alkenes by stereo- and regioselective
      stannyllithiation of diarylacetylenes.
AB  - Addition of trimethylstannyllithium to a diarylacetylene takes place exclusively
      in an anti-fashion to produce a lithio vinylstannane intermediate. The
      regioselectivity of the addition is controlled by the steric and electronic
      property of the acetylene and reaches up to >99:1. The two newly formed C-metal
      bonds can be sequentially and stereospecifically transformed into two new C-C
      bonds as illustrated by stereoselective synthesis of 4-hydroxytamoxifen and its
      regioisomer. A tetraarylethene bearing different aryl groups can be synthesized
      similarly and cyclized to a substituted dibenzo[g,p]chrysene derivative via a
      palladium-catalyzed arylation reaction.

PMID- 20698543
TI  - A healable supramolecular polymer blend based on aromatic pi-pi stacking and
      hydrogen-bonding interactions.
AB  - An elastomeric, healable, supramolecular polymer blend comprising a chain-folding
      polyimide and a telechelic polyurethane with pyrenyl end groups is compatibilized
      by aromatic pi-pi stacking between the pi-electron-deficient diimide groups and
      the pi-electron-rich pyrenyl units. This interpolymer interaction is the key to
      forming a tough, healable, elastomeric material. Variable-temperature FTIR
      analysis of the bulk material also conclusively demonstrates the presence of
      hydrogen bonding, which complements the pi-pi stacking interactions. Variable
      temperature SAXS analysis shows that the healable polymeric blend has a nanophase
      separated morphology and that the X-ray contrast between the two types of domain
      increases with increasing temperature, a feature that is repeatable over several
      heating and cooling cycles. A fractured sample of this material reproducibly
      regains more than 95% of the tensile modulus, 91% of the elongation to break, and
      77% of the modulus of toughness of the pristine material.

PMID- 20698542
TI  - Identification and development of novel inhibitors of Toxoplasma gondii enoyl
      reductase.
AB  - Toxoplasmosis causes significant morbidity and mortality, and yet available
      medicines are limited by toxicities and hypersensitivity. Because improved
      medicines are needed urgently, rational approaches were used to identify novel
      lead compounds effective against Toxoplasma gondii enoyl reductase (TgENR), a
      type II fatty acid synthase enzyme essential in parasites but not present in
      animals. Fifty-three compounds, including three classes that inhibit ENRs, were
      tested. Six compounds have antiparasite MIC(90)s < or = 6 microM without toxicity
      to host cells, three compounds have IC(90)s < 45 nM against recombinant TgENR,
      and two protect mice. To further understand the mode of inhibition, the cocrystal
      structure of one of the most promising candidate compounds in complex with TgENR
      has been determined to 2.7 A. The crystal structure reveals that the aliphatic
      side chain of compound 19 occupies, as predicted, space made available by
      replacement of a bulky hydrophobic residue in homologous bacterial ENRs by Ala in
      TgENR. This provides a paradigm, conceptual foundation, reagents, and lead
      compounds for future rational development and discovery of improved inhibitors of
      T. gondii.

PMID- 20698544
TI  - Doped assemblies of gold nanoparticles: structural and electronic properties.
AB  - We performed an ab initio study of molecular-doped periodic assemblies of ligand
      stabilized Au nanoparticles. We found that the most stable dopant positions are
      near the nanoparticle surfaces, away from the center of interstitial positions.
      The dopants provide an effective screening mechanism, strongly reducing the
      nanoparticles charging energies. We also found a linear dependence of the Fermi
      level with dopant concentration, consistent with recent experiments, up to a
      critical concentration. For larger concentrations, a new regime is predicted.
      These features are well reproduced by a simple, analytical model for the
      material.

PMID- 20698545
TI  - Dynamic dissolution: a step closer to predictive dissolution testing?
AB  - The use of compendial dissolution techniques to characterize the performance of
      oral drug delivery systems is an established area of pharmaceutical science.
      However, compendial equipment is recognized as being limited in its ability to
      replicate the dynamic aspects of in vivo dissolution that are associated with
      dosage form transit through a rapidly changing and complex gastrointestinal
      lumenal environment. This review provides an overview of noncompendial
      dissolution models which have been developed to address the deficiencies of the
      traditional dissolution bath and provide scientists with a way of assessing
      product performance under physiologically relevant conditions.

PMID- 20698546
TI  - Mesoscale carbon sequestration site screening and CCS infrastructure analysis.
AB  - We explore carbon capture and sequestration (CCS) at the meso-scale, a level of
      study between regional carbon accounting and highly detailed reservoir models for
      individual sites. We develop an approach to CO(2) sequestration site screening
      for industries or energy development policies that involves identification of
      appropriate sequestration basin, analysis of geologic formations, definition of
      surface sites, design of infrastructure, and analysis of CO(2) transport and
      storage costs. Our case study involves carbon management for potential oil shale
      development in the Piceance-Uinta Basin, CO and UT. This study uses new
      capabilities of the CO(2)-PENS model for site screening, including reservoir
      capacity, injectivity, and cost calculations for simple reservoirs at multiple
      sites. We couple this with a model of optimized source-sink-network
      infrastructure (SimCCS) to design pipeline networks and minimize CCS cost for a
      given industry or region. The CLEAR(uff) dynamical assessment model calculates
      the CO(2) source term for various oil production levels. Nine sites in a 13,300
      km(2) area have the capacity to store 6.5 GtCO(2), corresponding to shale-oil
      production of 1.3 Mbbl/day for 50 years (about 1/4 of U.S. crude oil production).
      Our results highlight the complex, nonlinear relationship between the spatial
      deployment of CCS infrastructure and the oil-shale production rate.

PMID- 20698547
TI  - Time course of congener uptake and elimination in rats after short-term
      inhalation exposure to an airborne polychlorinated biphenyl (PCB) mixture.
AB  - Despite the continued presence of PCBs in indoor and ambient air, few studies
      have investigated the inhalation route of exposure. While dietary exposure has
      declined, inhalation of the semivolatile, lower-chlorinated PCBs has risen in
      importance. We measured the uptake, distribution, and time course of elimination
      of inhaled PCB congeners to characterize the pulmonary route after short-term
      exposure. Vapor-phase PCBs were generated from Aroclor 1242 to a nose-only
      exposure system and characterized for congener levels and profiles. Rats were
      exposed via inhalation acutely (2.4 mg/m3 for 2 h) or subacutely (8.2 mg/m3, 2
      hx10 days), after which pulmonary immune responses and PCB tissue levels were
      measured. Animals acutely exposed were euthanized at 0, 1, 3, 6, and 12 h post
      exposure to assess the time course of PCB uptake and elimination. Following rapid
      absorption and distribution, PCBs accumulated in adipose tissue but decayed in
      other tissues with half-lives increasing in liver (5.6 h)<lung (8.2 h)<brain (8.5
      h)<blood (9.7 h). PCB levels were similar in lung, liver, and adipose tissue,
      lower in brain, and lowest in blood. Inhalation of the airborne PCB mixture
      contributed significantly to the body burden of lower-chlorinated congeners.
      Congeners detected in tissue were mostly ortho-substituted ranging from mono- to
      pentachlorobiphenyls. Selective uptake and elimination led to accumulation of a
      distinct congener spectrum in tissue. Minimal evidence of toxicity was observed.

PMID- 20698548
TI  - Torsionally responsive C3-symmetric azo dyes: azo-hydrazone tautomerism,
      conformational switching, and application for chemical sensing.
AB  - An efficient triple azo coupling reaction between anilines and phloroglucinol
      furnished a series of C(3)-symmetric molecules 7-9 supporting multiple
      conjugation pathways that converge at the molecular core. A combination of
      (1)H/(13)C NMR spectroscopy, X-ray crystallography, and density functional theory
      computational studies provided a coherent picture of the [n,pi]-conjugated
      molecular core, which is best described as the tris(hydrazone) [rather than
      tris(azo)] tautomer stabilized by resonance-assisted hydrogen bonding. For a
      homologous series of compounds, an increase in the torsional angles between the
      planar molecular core and the peripheral aryl groups results in a systematic blue
      shift in the low-energy electronic transitions (7, 523 nm; 8, 505 nm; 9, 445 nm
      in CHCl(3)) that qualitatively correlates with the shrinkage of effective
      conjugation through structural distortion. Similar spectral shifts could also be
      induced by amine substrates that interact with the intramolecular hydrogen
      bonding network to trigger bond-twisting motions. Specifically, a brief exposure
      of a thin film of 7 to vapor samples of butyl-, hexyl-, diethyl-, and
      diisopropylamine resulted in a rapid and reversible color change from pink to
      dark-orange. Under similar conditions, however, triethylamine did not elicit any
      detectable color change, despite the fact that it has a significantly higher
      vapor pressure than n-hexylamine. These findings implicate that the hydrogen
      bonding donor ability is a key requirement for the binding-induced conformational
      switching, which allows for direct naked-eye detection of volatile amines under
      ambient conditions.

PMID- 20698549
TI  - Using spectrophotometric titrations to characterize humic acid reactivity at
      environmental concentrations.
AB  - Potentiometric titration is a common method to characterize dissolved organic
      matter (DOM) reactivity. Because of the sensitivity of pH electrodes, it is
      necessary to work with very high DOM (>1 g/L) concentrations that are unrealistic
      compared to those found in natural waters (0.1 to 100 mg/L). To obtain proton
      binding data for concentrations closer to environmental values, spectroscopic
      titration methodology is a viable alternative to traditional potentiometric
      titrations. Spectrophotometric titrations and UV-visible spectra of a diluted
      solution of purified Aldrich humic acid (5 mgDOC/L) are used to estimate changes
      in proton binding moieties as function of pH and ionic strength after calculation
      of differential absorbance spectra variations. After electrostatic correction of
      spectrophotometric data, there is a linear operational correlation between
      spectrophotometric and potentiometric data which can be used as a transfer
      function between the two properties. Spectrophotometric titrations are then used
      to determine the changes of humic acid protonation after adsorption onto alpha
      alumina.

PMID- 20698550
TI  - In planta engineering of gold nanoparticles of desirable geometries by modulating
      growth conditions: an environment-friendly approach.
AB  - Unique properties of gold nanoparticles (AuNPs) can be achieved by manipulating
      their geometries. However, it is not known if the shapes and sizes of AuNPs can
      be modulated in planta. Here, we evaluated the accumulation of gold across
      taxonomically diverse plant species (alfalfa, cucumber, red clover, ryegrass,
      sunflower, and oregano). Significant variations were detected in the uptake of
      gold in the roots ranging from 500 ppm (ryegrass) to 2500 ppm (alfalfa). Alfalfa
      was selected for subsequent studies due to its ability to accumulate relatively
      large quantities of gold in its roots. Temporal analysis revealed that most of
      the AuNPs formed within 6 h of treatment, and the majority of them fall within
      the size range of 10-30 nm. Spherical AuNPs (1-50 nm) were detected ubiquitously
      across different treatments. To elucidate the effects of growth variables on the
      geometries of in planta synthesized AuNPs, alfalfa was subjected to KAuCl(4) (50
      ppm) treatment for 3d under different pH, temperature, and light regimes.
      Interestingly, manipulation of growth conditions triggered a noticeable shift in
      the relative abundance of spherical, triangular, hexagonal, and rectangular AuNPs
      providing empirical evidence toward the feasibility of their in planta
      engineering.

PMID- 20698551
TI  - Platinized WO3 as an environmental photocatalyst that generates OH radicals under
      visible light.
AB  - This study aims to understand the visible light photocatalytic activities of
      platinized WO3 (Pt/WO3) on the degradation of aquatic pollutants and the role of
      main photooxidants. The presence of Pt on WO3 is known to facilitate the
      multielectron reduction of O2, which enables O2 to serve as an electron acceptor
      despite the insufficient reduction potential of the conduction band electrons (in
      WO3) for the one-electron reduction of O2. The concurrent oxidative reactions
      occurring on WO3 were markedly enhanced in the presence of Pt and accompanied the
      production of OH radicals under visible light, which was confirmed by both a
      fluorescence method (using a chemical trap) and a spin trap method. The
      generation of OH radicals mainly comes from the reductive decomposition of H2O2
      that is produced in situ from the reduction of O2 on Pt/WO3. The rate of in situ
      production of H2O2 under visible light was significantly faster with Pt/WO3 than
      WO3. Six substrates that were tested for the visible light (lambda>420 nm)
      induced degradation on Pt/WO3 included dichloroacetate (DCA), 4-chlorophenol (4
      CP), tetramethylammonium (TMA), arsenite (As(III)), methylene blue (MB), and acid
      orange 7 (AO7). The degradation (or conversion) of all six substrates was
      successfully achieved with Pt/WO3 and the role of OH radicals in Pt/WO3
      photocatalysis seemed to be different depending on the kind of substrate. In the
      presence of tert-butyl alcohol (TBA: OH radical scavenger), the photocatalytic
      degradation was markedly reduced for 4-CP or completely inhibited for DCA and TMA
      whereas that of As(III), MB, and AO7 was little affected. Pt/WO3 photocatalyst
      that oxidizes various substrates under visible light with a sufficient
      photostability can be applied for solar water treatment.

PMID- 20698552
TI  - Hispolon suppresses SK-Hep1 human hepatoma cell metastasis by inhibiting matrix
      metalloproteinase-2/9 and urokinase-plasminogen activator through the PI3K/Akt
      and ERK signaling pathways.
AB  - Cancer metastasis is a primary cause of cancer death. Hispolon is an active
      phenolic compound of Phellinus linteus, a mushroom that has recently been shown
      to have antioxidant and anticancer activities. In this study, we first observed
      that hispolon exerted a dose-dependent inhibitory effect on invasion and
      motility, but not on adhesion, of the highly metastatic SK-Hep1 cells in the
      absence of cytotoxicity. Mechanistically, hispolon decreased the expression of
      matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and
      urokinase-plasminogen activator (uPA) in a concentration-dependent manner.
      Hispolon also inhibited phosphorylation of extracellular signaling-regulating
      kinase1/2 (ERK1/2), phosphatidylinositol-3-kinase/serine/threonine protein kinase
      (or protein kinase B (PI3K/Akt), and focal adhesion kinase (FAK). Furthermore,
      treatment of SK-Hep1 cells with an inhibitor specific for ERK1/2 (PD98256)
      decreased the expression of MMP-2, and MMP-9. These results demonstrate that
      hispolon can inhibit the metastasis of SK-Hep1 cells by reduced expression of MMP
      2, MMP-9, and uPA through the suppression of the FAK signaling pathway and of the
      activity of PI3K/Akt and Ras homologue gene family, member A (RhoA). These
      findings suggest that hispolon may be used as an antimetastatic agent.

PMID- 20698553
TI  - HBCD stereoisomer pattern in mirror carps following dietary exposure to pure
      gamma-HBCD enantiomers.
AB  - 1,2,5,6,9,10-hexabromocyclododecane (HBCD) is a brominated flame retardant
      consisting of a mixture of diastereomeric pairs of enantiomers that is a known
      omnipresent, environmental contaminant. The present study investigated the
      possibility of bioisomerization of HBCD stereoisomers. Therefore, mirror carps
      (Cyprinus carpio morpha noblis) were exposed to pure (+)- and (-)-gamma-HBCD,
      randomly sampled biweekly over a period of three and a half months and the
      fillets were subjected to enantiomer-specific determination of HBCD. Considering
      the background contamination of the fish at the beginning of the feeding period,
      significant enrichment of the respectively fed gamma-enantiomer was already
      detectable after two weeks of exposure. However, no significant enrichment of the
      respectively expected alpha-enantiomer was observed within this period. Thus, no
      evidence for the isomerization of HBCD stereoisomers was found in mirror carp
      under the applied conditions.

PMID- 20698554
TI  - Structure determination of neptunium(VI) mu3-hydroxobenzoate, [(NpO2)2(mu3
      OH)2(H5C6COO)2] x 2 H2O.
AB  - Neptunium(VI) benzoate with mu(3)-OH(-) has been isolated and studied by the X
      ray method. The main structural motive in the crystal is corrugated ribbons
      [(NpO(2))(2)(mu(3)-OH)(2)(C(7)H(5)O(2))(2)](n) extended along the c axes in which
      three neptunium pentagonal bipyramids are linked through the mu(3)-OH(-) ligand.
      The benzoate ions are arranged at both sides of the ribbons, and each anion binds
      two adjacent NpO(2). The water molecules are arranged in the channels along the c
      axis.

PMID- 20698555
TI  - Cellular uptake, cytotoxicity, and innate immune response of silica-titania
      hollow nanoparticles based on size and surface functionality.
AB  - Silica-titania hollow nanoparticles (HNPs) with uniform diameters of 25, 50, 75,
      100, and 125 nm were fabricated by dissolution and redeposition method in order
      to evaluate size dependent cellular response. Surface-modified HNPs with
      cationic, anionic, and neutral functional group were prepared by silane
      treatment. We systematically investigated cellular internalization, toxicity, and
      innate immune response of HNPs in human breast cancer (SK-BR-3) and mouse
      alveolar macrophage (J774A.1) cells. Size- and surface functionality-dependent
      cellular uptake of HNPs was investigated by fluorescence labeling (fluorescein
      isothiocyanate), inductively coupled plasma-emission spectroscopy, and
      ultrastructural resolution using transmission electron microscopy. Viability,
      reactive oxygen species, and apoptosis/necrosis of HNP-treated J774A.1 revealed
      the size-dependent phenomenon. Innate immune response of HNP-treated macrophages
      was measured by three cytokines such as interleukin-1, interleukin-6, and tumor
      necrosis factor alpha. Among the HNPs of different sizes, 50-nm HNPs demonstrated
      the highest toxic influence on macrophages. Among the HNPs with surface
      functionalities, cationic HNPs demonstrated the most toxic effect on J774A.1 and
      the highest uptake efficiency. The toxicity results of HNP-treated macrophages
      were consistent with the cellular internalization efficiency. These findings
      provide size- and surface functionality-dependent nanotoxicity and uptake of
      HNPs, and lead to HNPs for bioapplications such as drug delivery and imaging
      probe.

PMID- 20698556
TI  - On the existence of the chair conformation in six-membered ring phosphates
      bearing an aryl group axially oriented at the C4 position: cyclic nucleotides as
      model compounds for cyclic phosph(on)ate and phosphoramide prodrugs.
AB  - A series of cyclic nucleotide analogues to HepDirect prodrugs were prepared by a
      three-component reaction of protected thymine, phosphoryl chloride, and 5-aryl
      alpha-D-xylofuranoses derivatives. One of the cyclic nucleotides showed NMR data
      that suggest a predominant twisted conformation; however, in spite of having an
      aryl group at the C4 position within the crystal lattice, the cyclic nucleotide
      had a chair conformation with the aryl group axially oriented. By analyzing the
      unprecedented X-ray structure, it was observed that the oxygen atom from the
      phoshoryl group (P=O) is found in close proximity to the o-hydrogen atom of the
      aryl group (2.51 A), suggesting thus an attractive nonbonding electrostatic
      interaction, which might be the driving force that overcomes the steric diaxial
      interactions imposed by the aryl group. Theoretical studies (NBO) for two model
      compounds showed that there are indeed interactions between filled (donor) Lewis
      type NBOs and empty (acceptor) non-Lewis NBOs corresponding to the nO-->sigma*(C
      H) interaction. Additionally, conversion of a diastereomeric mixture of cyclic
      nucleotides into the more stable diastereomeric cyclic nucleotide was observed
      and explained by spontaneous isomerization in the phosphorinane ring. This
      finding supports the recently established hypothesis for the mode of action of
      prodrug cleavage, for which the anomeric effect plays an important role.

PMID- 20698557
TI  - Facile synthesis and luminescence of uniform Y2O3 hollow spheres by a sacrificial
      template route.
AB  - Uniform Y(2)O(3) hollow microspheres have been successfully prepared via a urea
      based homogeneous precipitation technique with colloidal melamine formaldehyde
      (MF) microspheres as templates followed by a subsequent calcination process. X
      ray diffraction, energy dispersive X-ray analysis, and Fourier transform infrared
      spectroscopy results show that the MF templates can be effectively removed, and
      the amorphous precursor has converted to crystalline Y(2)O(3) during the
      annealing process. Scanning electron microscopy and transmission electron
      microscopy images indicate that the Y(2)O(3) hollow spheres inherit a spherical
      shape and good dispersion of MF templates, and the shell of the hollow spheres is
      composed of a large amount of uniform nanoparticles. The lanthanide activator ion
      Ln(3+)-doped Y(2)O(3) hollow microspheres exhibit bright down- and upconversion
      luminescence with different colors coming from different activator ions under
      ultraviolet or 980 nm light excitation, which may find potential applications in
      fields such as light phosphor powders, advanced flat panel displays, or drug
      delivery.

PMID- 20698558
TI  - Quantum plasmonics: optical properties and tunability of metallic nanorods.
AB  - The plasmon resonances in metallic nanorods are investigated using fully quantum
      mechanical time-dependent density functional theory. The computed optical
      absorption curves display well-defined longitudinal and transverse plasmon
      resonances whose energies depend on the aspect ratio of the rods, in excellent
      agreement with classical electromagnetic modeling. The field enhancements
      obtained from the quantum mechanical calculations, however, differ significantly
      from classical predictions for distances shorter than 0.5 nm from the
      nanoparticle surfaces. These deviations can be understood as arising from the
      nonlocal screening properties of the conduction electrons at the nanoparticle
      surface.

PMID- 20698559
TI  - C-9 fluorenyl substituted anthracenes: a promising new family of blue luminescent
      materials.
AB  - Syntheses, optical, and electrochemical properties of novel C-9 fluorenyl
      substituted anthracenes linked by a tetrahedral sp(3)-hybridized carbon atom are
      reported for blue light emitting materials. Remarkably, an unoptimized organic
      light-emitting diode based on 1-fold fluorene-functionalized anthracene 3
      exhibits a radiance of 4100 cd/m(2) at 12 V and a maximum EL efficiency of 1.36
      cd/A with color purity CIE x, y (0.157, 0.082), which is very close to the
      National Television System Committee standard blue.

PMID- 20698560
TI  - Stereomutation of axially chiral aryl coumarins.
AB  - Coumarins substituted by an aryl group in position 4 display restricted rotation
      about the Ar-C4 bond, giving rise to conformational or configurational
      enantiomers (atropisomers) when such a restricted motion leads to a C(1)
      symmetry. The dynamics of the stereomutation processes of these axial enantiomers
      was monitored by dynamic NMR, dynamic enantioselective HPLC, or racemization
      kinetics, depending on the activation energies involved. These results were
      further supported by DFT computations. In the two cases where the enantiomers
      were sufficiently long living as to be physically separated at ambient
      temperature, the absolute configuration was determined by means of a theoretical
      simulation of their electronic circular dichroism spectra (ECD).

PMID- 20698561
TI  - Evaluation of heterogeneous metal-organic framework organocatalysts prepared by
      postsynthetic modification.
AB  - A metal-organic framework (MOF) containing 2-amino-1,4-benzenedicarboxylate
      (NH(2)-BDC) as a building block is shown to undergo chemical modification with a
      set of cyclic anhydrides. The modification of the aluminum-based MOF known as MIL
      53(Al)-NH(2) (MIL = Material Institut Lavoisier) by these reagents is
      demonstrated by using a variety of methods, including NMR and electrospray
      ionization mass spectrometry (ESI-MS), and the structural integrity of the
      modified MOFs has been confirmed by thermal gravimetric analysis (TGA) and powder
      X-ray diffraction (PXRD). Reaction with these cyclic anhydrides produces MOFs
      that display carboxylic acid functional groups within their pores. Furthermore,
      it is shown that maleic acid functionalized MIL-53(Al)-AMMal can act as a
      Bronsted acid catalyst and facilitate the methanolysis of several small epoxides.
      Experiments show that MIL-53(Al)-AMMal acts in a heterogeneous manner and is
      recyclable with consistent activity over at least three catalytic cycles. The
      findings presented here demonstrate several important features of covalent
      postsynthetic modification (PSM) on MOFs, including (1) facile introduction of
      catalytic functionality using simple organic reagents (e.g., anhydrides); (2) the
      ability to utilize and recycle organocatalytic MOFs; (3) control of catalytic
      activity through choice of functional group. The findings clearly illustrate that
      covalent postsynthetic modification represents a powerful means to access new MOF
      compounds that serve as organocatalytic materials.

PMID- 20698562
TI  - Reducing docking score variations arising from input differences.
AB  - The variability of docking results as a function of variations in ligand input
      conformations was studied for the GOLD, Glide, FlexX, and Surflex programs. It is
      concluded that there are two major effects leading to such variability: the
      adequacy of conformational search during docking and random "chaotic" effects
      arising from sensitivity to small input perturbations. It is shown that although
      the former is generally the stronger effect, the latter is also highly
      significant for almost all docking engines. The strong target-to-target variation
      of the magnitude of these effects is emphasized. The performance of different
      packages is compared using these measures. Guidelines are provided for different
      programs to reduce variability and improve reproducibility, which involve using a
      small number of input conformations as starting points for docking, followed by
      the selection of the top scoring docked pose from the results as the best docked
      solution.

PMID- 20698563
TI  - Relaxation dynamics of tryptophan in water: A UV fluorescence up-conversion and
      molecular dynamics study.
AB  - We report on an ultrafast experimental and simulations study of the early
      relaxation events of photoexcited tryptophan in water. Experimentally, we used
      fluorescence up-conversion in both polychromatic and single wavelength detection
      modes in the 300-480 nm range with polarization dependence. We report on the time
      evolution of the Stokes shift, bandwidth, and anisotropy from tens of
      femtoseconds to picoseconds. These observables contain signatures of the
      simultaneous occurrence of intramolecular and solvent-molecule interactions,
      which we disentangle with the help of nonequilibrium molecular dynamics
      simulations. We also observe a breakdown of the linear response approximation to
      describe our results.

PMID- 20698564
TI  - Effect of electron beam irradiation on postharvest quality and selected enzyme
      activities of the white button mushroom, Agaricus bisporus.
AB  - Agaricus bisporus fruit bodies were exposed to different doses (1, 2, 3, and 4
      kGy) of electron beam irradiation (EBI), and various physiological changes
      associated with postharvest deterioration, as well as selected enzymes considered
      to play a role in senescence, were monitored over a subsequent 16-day storage
      period at 4 degrees C and 75-85% relative humidity. EBI retarded postharvest
      mushroom softening and overall increases in malondialdehyde levels were more
      pronounced in controls compared with those of the irradiated samples. After 10
      days of storage, polyphenoloxidase activity in samples irradiated with 1-4 kGy
      doses was significantly (P<0.05) lower compared to that in control samples.
      Superoxide dismutase activity generally declined throughout the postharvest
      storage period in both irradiated and control samples, but no clear correlation
      between enzyme activity and EBI dosage was evident. Catalase activity decreased
      more slowly and to a lesser extent in fruit bodies exposed to 1 kGy compared with
      that in the controls and the other irradiated samples.

PMID- 20698565
TI  - Fast preparation procedure for large, flat cellulose and cellulose/inorganic
      nanopaper structures.
AB  - Nanostructured materials are difficult to prepare rapidly and as large
      structures. The present study is thus significant because a rapid preparation
      procedure for large, flat, smooth, and optically transparent cellulose nanopaper
      structures is developed using a semiautomatic sheet former. Cellulose/inorganic
      hybrid nanopaper is also produced. The preparation procedure is compared with
      other approaches, and the nanopaper structures are tested in uniaxial tensile
      tests. Optical transparency and high tensile strength are demonstrated in 200 mm
      diameter nanopaper sheets, indicating well-dispersed nanofibrils. The preparation
      time is 1 h for a typical nanopaper thickness of 60 MUm. In addition, the
      application of the nanopaper-making strategy to cellulose/inorganic hybrids
      demonstrates the potential for "green" processing of new types of nanostructured
      functional materials.

PMID- 20698566
TI  - All-amorphous-oxide transparent, flexible thin-film transistors. Efficacy of
      bilayer gate dielectrics.
AB  - Optically transparent and mechanically flexible thin-film transistors (TF-TFTs)
      composed exclusively of amorphous metal oxide films are fabricated on plastic
      substrates by combining an amorphous Ta(2)O(5)/SiO(x) bilayer transparent oxide
      insulator (TOI) gate dielectric with an amorphous zinc-indium-tin oxide (a-ZITO)
      transparent oxide semiconductor (TOS) channel and a-ZITO transparent oxide
      conductor (TOC) electrodes. The bilayer gate dielectric is fabricated by the post
      cross-linking of vapor-deposited hexachlorodisiloxane-derived films to form thin
      SiO(x) layers (v-SiO(x)) on amorphous Ta(2)O(5) (a-Ta(2)O(5)) films grown by ion
      assisted deposition at room temperature. The a-Ta(2)O(5)/v-SiO(x) bilayer TOI
      dielectric integrates the large capacitance of the high dielectric constant a
      Ta(2)O(5) layer with the excellent dielectric/semiconductor interfacial
      compatibility of the v-SiO(x) layer in a-ZITO TOS-based TF-TFTs. These all
      amorphous-oxide TF-TFTs, having a channel length and width of 100 and 2000
      microm, respectively, perform far better than a-Ta(2)O(5)-only devices and
      exhibit saturation-regime field-effect mobilities of approximately 20 cm(2)/V x
      s, on-currents >10(-4) A, and current on-off ratios >10(5). These TFTs operate at
      low voltages (approximately 4.0 V) and exhibit good visible-region optical
      transparency and excellent mechanical flexibility.

PMID- 20698567
TI  - Bronsted analysis and rate-limiting steps for the T5 flap endonuclease catalyzed
      hydrolysis of exonucleolytic substrates.
AB  - During replication and repair flap endonucleases (FENs) catalyze endonucleolytic
      and exonucleolytic (EXO) DNA hydrolyses. Altering the leaving group pK(a), by
      replacing the departing nucleoside with analogues, had minimal effect on
      k(cat)/K(M) in a T5FEN-catalyzed EXO reaction, producing a very low Bronsted
      coefficient, beta(lg). Investigation of the viscosity dependence of k(cat)/K(M)
      revealed that reactions of EXO substrates are rate limited by diffusional
      encounter of enzyme and substrate, explaining the small beta(lg). However, the
      maximal single turnover rate of the FEN EXO reaction also yields a near zero
      beta(lg). A low beta(lg) was also observed when evaluating k(cat)/K(M) for
      D201I/D204S FEN-catalyzed reactions, even though these reactions were not
      affected by added viscogen. But an active site K83A mutant produced a beta(lg) = 
      1.2 +/- 0.10, closer to the value observed for solution hydrolysis of phosphate
      diesters. The pH-maximal rate profiles of the WT and K83A FEN reactions both
      reach a maximum at high pH and do not support an explanation of the data that
      involves catalysis of leaving group departure by Lys 83 functioning as a general
      acid. Instead, a rate-limiting physical step, such as substrate unpairing or
      helical arch ordering, that occurs after substrate association must kinetically
      hide an inherent large beta(lg). It is suggested that K83 acts as an
      electrostatic catalyst that stabilizes the transition state for phosphate diester
      hydrolysis. When K83 is removed from the active site, chemistry becomes rate
      limiting and the leaving group sensitivity of the FEN-catalyzed reaction is
      revealed.

PMID- 20698569
TI  - Simulating fasted human intestinal fluids: understanding the roles of lecithin
      and bile acids.
AB  - The purpose of this work is to evaluate the roles of lecithin and bile salts in a
      new generation of fasted simulated small intestinal fluid (FaSSIF-II), thus
      enhancing the closer mimic of simulated fluids to the real human intestinal
      fluids (HIF) in drug discovery and drug product development. To assess the
      effects of lecithin in FaSSIF-II, solubility studies were conducted at 37 
      degrees C using four media including first generation simulated intestinal fluid
      (FaSSIF-I), FaSSIF-II, phosphate pH 6.5 buffer, and HIF. A total of 24 model
      compounds representing a wide range of biopharmaceutic properties were included.
      The drug solubility values measured in the FaSSIF-II were compared with those in
      FaSSIF-I, pH 6.5 buffer and HIF. To assess the effects of bile acids, solubility
      was measured for 4 compounds in the FaSSIF-I containing five different bile acids
      of various concentrations. The lecithin concentration in the FaSSIF-II is lowered
      from 0.75 mM to 0.2 mM. The results suggested that the FaSSIF-II is a better
      medium to reflect HIF, compared with pH 6.5 phosphate buffer and FaSSIF-I.
      Solubility of neutral compounds including atovaquone, carbamazepine,
      cyclosporine, danazol, diethylstilbestrol, felodipine, griseofulvin and probucol
      in FaSSIF-II showed improvement in predicting the in vivo solubility. The
      relative standard deviation (SD) of solubility measurement in FaSSIF-II is
      comparable with FaSSIF-I. For the acidic and basic tested compounds, the FaSSIF
      II performs similarly to the FaSSIF-I. Experimental results showed that the level
      of bile salts typically is less than 5 mM under fasted state. Among the five
      studied bile acids, the conjugation (glycine or taurine) has no impact on the
      drug solubilization, while there may be a minimal effect of the degree of
      hydroxylation of the steroid ring system on solubilization. The lecithin
      concentration of 0.2 mM in FaSSIF-II has been demonstrated to closely represent
      HIF, for both neutral and ionizable compounds. In the composition of simulated
      intestinal fluids, the structure of bile acids has minimal effect, providing the
      flexibility of choosing one bile salt to represent complex in vivo bile acids.

PMID- 20698568
TI  - Describing the mechanism of antimicrobial peptide action with the interfacial
      activity model.
AB  - Antimicrobial peptides (AMPs) have been studied for three decades, and yet a
      molecular understanding of their mechanism of action is still lacking. Here we
      summarize current knowledge for both synthetic vesicle experiments and microbe
      experiments, with a focus on comparisons between the two. Microbial experiments
      are done at peptide to lipid ratios that are at least 4 orders of magnitude
      higher than vesicle-based experiments. To close the gap between the two
      concentration regimes, we propose an "interfacial activity model", which is based
      on an experimentally testable molecular image of AMP-membrane interactions. The
      interfacial activity model may be useful in driving engineering and design of
      novel AMPs.

PMID- 20698570
TI  - Fluorescence of natural DNA: from the femtosecond to the nanosecond time scales.
AB  - The fluorescence of calf thymus DNA is studied by steady-state and time-resolved
      spectroscopy combining fluorescence upconversion and time-correlated single
      photon counting. The fluorescence spectrum is very similar to that of a
      stoichiometric mixture of monomeric chromophores, arising from bright pi pi*
      states, and contrasts with the existing picture of exciplex emission in natural
      DNA. Yet, the DNA fluorescence decays span over five decades of time, with 98% of
      the photons being emitted at times longer than 10 ps. These findings, in
      association with recent studies on model duplexes, are explained by the
      involvement of dark states, possibly related to charge separation, serving as a
      reservoir for the repopulation of the bright pi pi* states.

PMID- 20698571
TI  - Structure of CyanoP at 2.8 A: implications for the evolution and function of the
      PsbP subunit of photosystem II .
AB  - We present here the crystal structure of CyanoP (Tlr2075) from
      Thermosynechococcus elongatus at 2.8 A. CyanoP is a substoichiometric component
      of the isolated cyanobacterial Photosystem II (PSII) complex, distantly related
      to the PsbP extrinsic subunit of the oxygen-evolving PSII complex in higher
      plants and green algae. Despite the relatively low degree of sequence similarity,
      we have found that CyanoP adopts the same beta-sandwich fold as higher-plant PsbP
      and contains a well-conserved metal (zinc)-binding site that is also present in
      plant PsbP. Our results support the idea that CyanoP represents the basal
      structural fold of the PsbP superfamily.

PMID- 20698572
TI  - Large-scale prediction of human protein-protein interactions from amino acid
      sequence based on latent topic features.
AB  - Protein-protein interaction (PPI) is at the core of the entire interactomic
      system of any living organism. Although there are many human protein-protein
      interaction links being experimentally determined, the number is still relatively
      very few compared to the estimation that there are ~300,000 protein-protein
      interactions in human beings. Hence, it is still urgent and challenging to
      develop automated computational methods to accurately and efficiently predict
      protein-protein interactions. In this paper, we propose a novel hierarchical LDA
      RF (latent dirichlet allocation-random forest) model to predict human protein
      protein interactions from protein primary sequences directly, which is featured
      by a high success rate and strong ability for handling large-scale data sets by
      digging the hidden internal structures buried into the noisy amino acid sequences
      in low dimensional latent semantic space. First, the local sequential features
      represented by conjoint triads are constructed from sequences. Then the
      generative LDA model is used to project the original feature space into the
      latent semantic space to obtain low dimensional latent topic features, which
      reflect the hidden structures between proteins. Finally, the powerful random
      forest model is used to predict the probability for interaction of two proteins.
      Our results show that the proposed latent topic feature is very promising for PPI
      prediction and could also become a powerful strategy to deal with many other
      bioinformatics problems. As a web server, LDA-RF is freely available at
      http://www.csbio.sjtu.edu.cn/bioinf/LR_PPI for academic use.

PMID- 20698573
TI  - A new lower limit for the ultimate breaking strain of carbon nanotubes.
AB  - We apply immense strain to ultralong, suspended, single-walled carbon nanotubes
      while monitoring their Raman spectra. We can achieve strains up to 13.7 +/- 0.3%
      without slippage, breakage, or defect formation based on the observation of
      reversible change in Raman spectra. This is more than twice that of previous
      observations. The rate of G band downshift with strain is found to span a wide
      range from -6.2 to -23.6 cm(-1)/% strain. Under these immense strains, the G band
      is observed to downshift by up to 157 cm(-1) (from 1592 to 1435 cm(-1)).
      Interestingly, under these significant lattice distortions, we observe no
      detectable D band Raman intensity. Also, we do not observe any broadening of the
      G band line width until a threshold downshift of Deltaomega(G) > 75 cm(-1) is
      achieved at high strains, beyond which the fwhm of the G band increases sharply
      and reversibly. On the basis of a theoretical nonlinear stress-strain response,
      we estimate the maximum applied stress of the nanotubes in this study to be 99
      GPa with a strength-to-weight ratio of almost 74,000 kN x m/kg, which is 30 times
      that of Kevlar and 117 times that of steel.

PMID- 20698574
TI  - Vaccine delivery by polymeric vehicles in the mouse reproductive tract induces
      sustained local and systemic immunity.
AB  - Design of easily administered vaccines to protect the female reproductive tract
      against STIs such as HIV, HPV and HSV is a major step in improving world health
      standards. However, the effect of immunization routes and regimens (prime/boost)
      on immune response is not well-understood. Here, we present a systematic study of
      vaccine delivery by different routes and prime/boosting regimens to produce a
      robust humoral immune response in the reproductive tract. A model antigen,
      ovalbumin (OVA), was delivered orally or intranasally via polymer particles, and
      intravaginally via polymer disks to female mice. Repeated prime/boost at a single
      site result in high OVA-specific antibody levels in the serum for mice immunized
      orally (IgA) and invaginally (IgA and IgG) after 3 months. Vaginal antibody
      titers were the highest for mice immunized by intravaginal routes. Vaginal
      boosting following intranasal or oral priming did not appear to offer similar
      advantages to those primed intravaginally. Systemic immunization with OVA in
      Freund's adjuvant produced robust serum IgG levels, but little serum IgA or
      antibodies in the vaginal washings. All immunization schemes produced a
      significant level of IgG in the intestinal mucosa, with the exception of nasal
      priming followed by intravaginal boost with slow-releasing disks. In contrast,
      only immunization by nasal priming and intravaginal boost with fast-releasing
      disks was able to achieve significantly high intestinal IgA titers.

PMID- 20698575
TI  - Selection for nonamyloidogenic mutants of islet amyloid polypeptide (IAPP)
      identifies an extended region for amyloidogenicity.
AB  - The aggregation of the 37-residue protein, islet amyloid polypeptide (IAPP), as
      either insoluble amyloid or as small oligomers, appears to play a direct role in
      the death of pancreatic beta-islet cells in type II diabetes. While IAPP has been
      known to be the primary component of type II diabetes amyloid, the molecular
      interactions responsible for this aggregation have not been identified. To
      identify the aggregation-prone region(s), we constructed a library of randomly
      generated point mutants of IAPP. This mutant IAPP library was expressed in
      Escherichia coli as genetic fusions to the reporter protein enhanced green
      fluorescent protein (EGFP). Because IAPP aggregates rapidly, both independently
      and when fused to EGFP, the fusion protein does not yield a functional,
      fluorescent EGFP. However, mutations of IAPP that result in nonamyloidogenic
      sequences remain soluble and allow EGFP to fold and fluoresce. Using this screen,
      we identified 22 single mutations, 4 double mutations, and 2 triple mutations of
      IAPP that appear to be less amyloidogenic than wild-type human IAPP. A comparison
      of these sequences suggests residues 13 and 15-17 comprise an additional
      aggregation-prone region outside of the main amyloidogenic region of IAPP.

PMID- 20698577
TI  - Characterization of Murine Brain Membrane Glycoproteins by Detergent Assisted
      Lectin Affinity Chromatography.
AB  - Membrane glycoproteins play vital roles in many fundamental physiological and
      pathophysiological processes in the central nervous system and represent
      important targets for pharmaceuticals and biomarker discovery. However, their
      isolation and characterization have been greatly limited. Lectin affinity
      chromatography (LAC) has evolved as a powerful method to enrich glycoproteins in
      biofluid and cell/tissue lysate. However, its use in the hydrophobic fraction of
      the samples has rarely been explored. In this study, we have conducted a
      systematic investigation on the lectin binding efficiency in the presence of four
      commonly used detergents. We have found that, under certain concentrations,
      detergents can minimize nonspecific binding and facilitate the elution of
      hydrophobic glycoproteins. With the detergent assisted lectin affinity
      chromatography (DALAC), a total of 1491 proteins were identified with low numbers
      of false positives from two lectins. Proteins (699) were identified with at least
      two unique peptides, of which 219 are membrane glycoproteins. Compared to the
      traditional methods, the DALAC approach significantly increased the recovery of
      plasma membrane and glycoproteins. NP-40 is recommended as a well rounded
      detergent for DALAC, but the conditions for enriching certain target proteins
      need to be empirically determined. This study represents the first global
      identification of the murine brain glycoproteome.

PMID- 20698576
TI  - Transport and metabolism of radiolabeled choline in hepatocellular carcinoma.
AB  - Altered choline (Cho) metabolism in cancerous cells can be used as a basis for
      molecular imaging with PET using radiolabeled Cho. In this study, the metabolism
      of tracer Cho was investigated in a woodchuck hepatocellular carcinoma (HCC) cell
      line (WCH17) and in freshly derived rat hepatocytes. The transporter responsible
      for [(11)C]-Cho uptake in HCC was also characterized in WCH17 cells. The study
      helped to define the specific mechanisms responsible for radio-Cho uptake seen on
      the PET images of primary liver cancer such as HCC. Cells were pulsed with
      [(14)C]-Cho for 5 min and chased for varying durations in cold media to simulate
      the rapid circulation and clearance of [(11)C]-Cho. Radioactive metabolites were
      extracted and analyzed by radio-HPLC and radio-TLC. The Cho transporter (ChoT)
      was characterized in WCH17 cells. WCH17 cells showed higher (14)C uptake than rat
      primary hepatocytes. [(14)C]-Phosphocholine (PC) was the major metabolite in
      WCH17. In contrast, the intracellular Cho in primary hepatocytes was found to be
      oxidized to betaine (partially released into media) and, to a lesser degree,
      phosphorylated to PC. [(14)C]-Cho uptake by WCH17 cells was found to have both
      facilitative transport and nonfacilitative diffusion components. The facilitative
      transport was characterized by Na(+) dependence and low affinity (K(m) = 28.59 +/
      6.75 MUM) with partial energy dependence. In contrast, ChoT in primary
      hepatocytes is Na(+) independent and low affinity. Our data suggest that
      transport and phosphorylation of Cho are responsible for the tracer accumulation
      during [(11)C]-Cho PET imaging of HCC. WCH17 cells incorporate [(14)C]-Cho
      preferentially into PC. Conversion of [(14)C]-PC into phosphatidylcholine
      occurred slowly in vitro. Basal oxidation and phosphorylation activities in
      surrounding hepatic tissue contribute to the background seen in [(11)C]-Cho PET
      images.

PMID- 20698578
TI  - Minimizing tissue damage in electroosmotic sampling.
AB  - Electroosmotic sampling is a potentially powerful method for pulling
      extracellular fluid into a fused-silica capillary in contact with the surface of
      tissue. An electric field is created in tissue by passing current through an
      electrolyte-filled capillary and then through the tissue. The resulting field
      acts on the counterions to the surface charges in the extracellular space to
      create electroosmotic fluid flow within the extracellular space of a tissue. Part
      of the development of this approach is to define conditions under which
      electroosmotic sampling minimizes damage to the tissue, in this case organotypic
      hippocampal slice cultures (OHSCs). We have assessed tissue damage by measuring
      fluorescence resulting from exposing sampled tissue to propidium iodide solution
      16-24 h after sampling. Sampling has been carried out with a variety of capillary
      diameters, capillary tip-tissue distances, and applied voltages. Tissue damage is
      negligible when the power (current x potential drop) created in the tissue is
      less than 120 microW. In practical terms, smaller capillary i.d.s, lower
      voltages, and greater tissue to capillary distances lead to lower power.

PMID- 20698579
TI  - Quantification in Gas Chromatography: Prediction of Flame Ionization Detector
      Response Factors from Combustion Enthalpies and Molecular Structures.
AB  - In a previous report, we validated the use of a database that compiled the
      relative response factors of flavor and fragrance compounds under standard GC
      conditions for a flame ionization detector. Here we investigate the prediction of
      unknown response factors from the molecular structure by using combustion
      enthalpies. In a first step, this enthalpy was well-predicted with either ab
      initio calculation or multiple linear regression based on the molecular formula.
      In a second step, good correlation was observed between these combustion
      enthalpies and experimental relative response factors, and so the response
      factors were predictable from only the molecular formula. With a database of 351
      compounds, about 60% of them exhibited a difference of less than 5% between the
      predicted and experimental relative response factors and about 80% exhibited a
      difference of less than 10%.

PMID- 20698580
TI  - Quantification of gemcitabine incorporation into human DNA by LC/MS/MS as a
      surrogate measure for target engagement.
AB  - In this study, we report a method for direct determination of gemcitabine
      incorporation into human DNA. Gemcitabine (dFdC), a structural analog of the
      nucleoside deoxycytidine (dC), derives its primary antitumor activity through
      interruption of DNA synthesis. Unlike other surrogate measures, DNA incorporation
      provides a mechanistic end point useful for dose optimization. DNA samples (ca.
      25 microg) were hydrolyzed using a two-step enzymatic procedure to release dFdC
      which was subsequently quantified by LC-ESI-MS/MS using stable isotope labeled
      internal standards and selected reaction monitoring (SRM). dFdC was quantitated
      and reported relative to deoxyguanosine (dG) since dG is the complementary base
      for both dFdC and dC. The SRM channel for dG was detuned using collision energy
      as the attenuating parameter in order to accommodate the difference in relative
      abundance for these two analytes (>104) and enable simultaneous quantification
      from the same injection. The assay was shown to be independent of the amount of
      DNA analyzed. The method was validated for clinical use using a 3 day procedure
      assessing precision, accuracy, stability, selectivity, and robustness. The
      validated ranges for dFdC and dG were 5-7500 pg/mL and 0.1-150 microg/mL,
      respectively. Results are presented which confirm that the ratio of dFdC to dG in
      DNA isolated from tumor cells incubated with dFdC increases with increased
      exposure to the drug and that dFdC can also be quantified from DNA extracted from
      blood.

PMID- 20698581
TI  - Study of Discontinuous Atmospheric Pressure Interfaces for Mass Spectrometry
      Instrumentation Development.
AB  - The discontinuous atmospheric pressure interface (DAPI) has allowed the transfer
      of ions from atmospheric pressure ionization sources to an ion trap mass analyzer
      in hand-held mass spectrometers with miniature pumping systems at transfer
      efficiencies high enough for proper chemical analysis. The DAPI potentially would
      allow a significant enhancement to the mass analysis efficiency of laboratory
      scale mass spectrometers, which have pumping systems of much larger capacities. A
      laboratory-scale mass spectrometer with a DAPI-RIT (rectilinear ion trap)-DAPI
      configuration has been developed to explore this possibility. The gas dynamic
      effects on ion trapping and mass analysis have been studied at various
      conditions. A pulsed nanoelectrospray ionization source synchronized with the
      DAPI has been implemented to improve the sample usage efficiency as well as to
      adjust the number of ions to be trapped for MS analysis, so that space charge
      effects can be avoided. Single-scan spectra of peptides were recorded with an
      ionization time as short as 1 mus, corresponding to an analyte consumption of
      several attomoles. The simplicity of application of the DAPI for performing
      ion/molecule and ion/ion reactions has also been demonstrated with proton
      transfer and electron transfer dissociation reactions with peptides.

PMID- 20698582
TI  - High-Throughput Phospholipidic Fingerprinting by Online Desorption of Dried Spots
      and Quadrupole-Linear Ion Trap Mass Spectrometry: Evaluation of Atherosclerosis
      Biomarkers in Mouse Plasma.
AB  - This work presents a strategy for the evaluation of differences in plasma
      phospholipid content between atherosclerotic and healthy mice from micro volumes
      (2 muL) spotted on filter paper. Dried plasma spots (DPS) were directly desorbed
      into a triple quadrupole linear ion trap mass spectrometer using a homemade
      prototype, ensuring high-throughput analysis of dried spots without any sample
      pretreatment. Multiple positive and negative neutral loss and precursor ion scans
      were simultaneously acquired in a single loop, allowing oriented fingerprinting
      until 2700 potential species including phosphatidic acid (PA),
      phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylglycerol
      (PG), phosphatidylinositol (PI), phosphatidylserine (PS), and sphingomyelin (SM)
      classes. The phospholipidic variations between 15 healthy and 15 atherosclerotic
      mice were evaluated using t tests, matrix reduction and merging, and principal
      component analysis (PCA) as a chemometric statistical approach. The
      discriminating ions in PCA analysis were qualitatively identified in an
      information dependent acquisition (IDA) manner using enhanced resolution and
      enhanced product ion scans. PCA demonstrates a clear clustering between healthy
      and diseased mice. Regarding the most relevant variables identified, this
      procedure has confirmed the role of SM and PS classes in atherosclerosis and has
      established potential biomarkers shown to be significantly up- or down-regulated
      with the disease. The results presented in this work demonstrate the sample
      processing and analysis potential of the developed strategy to evaluate new
      biomarkers and the state of a disease.

PMID- 20698583
TI  - Absolute measurements of total peroxy nitrate mixing ratios by thermal
      dissociation blue diode laser cavity ring-down spectroscopy.
AB  - Peroxycarboxylic nitric anhydrides (PANs) have long been recognized as important
      trace gas constituents of the troposphere. Here, we describe a blue diode laser
      thermal dissociation cavity ring-down spectrometer for rapid and absolute
      measurements of total peroxyacyl nitrate (SigmaPAN) abundances at ambient
      concentration levels. The PANs are thermally dissociated and detected as NO2,
      whose mixing ratios are quantified by optical absorption at 405 nm relative to a
      reference channel kept at ambient temperature. The effective NO2 absorption cross
      section at the diode laser emission wavelength was measured to be 6.1 x 10(-19)
      cm2 molecule(-1), in excellent agreement with a prediction based on a projection
      of a high-resolution literature absorption spectrum onto the laser line width.
      The performance, i.e., accuracy and precision of measurement and matrix effects,
      of the new 405 nm thermal dissociation cavity ring-down spectrometer was
      evaluated and compared to that of a 532 nm thermal dissociation cavity ring-down
      spectrometer using laboratory-generated air samples. The new 405 nm spectrometer
      was considerably more sensitive and compact than the previously constructed
      version. The key advantage of laser thermal dissociation cavity ring-down
      spectroscopy is that the measurement can be considered absolute and does not need
      to rely on external calibration.

PMID- 20698584
TI  - Human serum processing and analysis methods for rapid and reproducible N-glycan
      mass profiling.
AB  - Glycans constitute a new class of compounds for biomarker discovery.
      Glycosylation is a common post-translational modification and is often associated
      with transformation to malignancy. To analyze glycans, they are released from
      proteins, enriched, and measured with mass spectrometry. For biomarker discovery,
      repeatability at every step of the process is important. Locating and minimizing
      the process variability is key to establishing a robust platform stable enough
      for biomarker discovery. Understanding the variability of the measurement devices
      helps understand the variability associated with the chemical processing. This
      report explores the potential use of methods expediting the enzymatic release of
      glycans such as a microwave reactor and automation of the solid-phase extraction
      with a robotic liquid handler. The study employs matrix-assisted laser
      desorption/ionization-Fourier transform ion cyclotron resonance mass spectrometry
      but would be suitable with any mass spectrometry method. Methods for system-wide
      data analysis are examined because proper metrics for evaluating the performance
      of glycan sample preparation procedures are not well established.

PMID- 20698586
TI  - Plasmonic nanoparticle arrays with nanometer separation for high-performance SERS
      substrates.
AB  - We demonstrate a method for fabricating arrays of plasmonic nanoparticles with
      separations on the order of 1 nm using an angle evaporation technique. Samples
      fabricated on thin SiN membranes are imaged with high-resolution transmission
      electron microscopy (HRTEM) to resolve the small separations achieved between
      nanoparticles. When irradiated with laser light, these nearly touching metal
      nanoparticles produce extremely high electric field intensities, which result in
      surface-enhanced Raman spectroscopy (SERS) signals. We quantify these
      enhancements by depositing a p-aminothiophenol dye molecule on the nanoparticle
      arrays and spatially mapping their Raman intensities using confocal micro-Raman
      spectroscopy. Our results show significant enhancement when the incident laser is
      polarized parallel to the axis of the nanoparticle pairs, whereas no enhancement
      is observed for the perpendicular polarization. These results demonstrate proof
      of-principle of this fabrication technique. Finite difference time domain
      simulations based on HRTEM images predict an electric field intensity enhancement
      of 82400 at the center of the nanoparticle pair and an electromagnetic SERS
      enhancement factor of 10(9)-10(10).

PMID- 20698585
TI  - Galectin-3 is a candidate biomarker for amyotrophic lateral sclerosis: discovery
      by a proteomics approach.
AB  - The discovery of biomarkers for neurodegenerative diseases will have a major
      impact on the efficiency of therapeutic clinical trials and may be important for
      understanding basic pathogenic mechanisms. We have approached the discovery of
      protein biomarkers for amyotrophic lateral sclerosis (ALS) by profiling affected
      tissues in a relevant animal model and then validating the findings in human
      tissues. Ventral roots from SOD1(G93A) "ALS" mice were analyzed by label-free
      quantitative mass spectrometry, and the resulting data were compared with data
      for matched samples from nontransgenic littermates and transgenic mice carrying
      wild-type human SOD1 (SOD1(WT)). Of 1299 proteins, statistical inference of the
      data in the three groups identified 14 proteins that were dramatically altered in
      the ALS mice compared with the two control groups. The protein galectin-3 emerged
      as a lead biomarker candidate on the basis of its differential expression as
      assessed by immunoblot and immunocytochemistry in SOD1(G93A) mice as compared to
      controls and because it is a secreted protein that could potentially be measured
      in human biofluids. Spinal cord tissue from ALS patients also exhibited increased
      levels of galectin-3 when compared to controls. Further measurement of galectin-3
      in cerebrospinal fluid samples showed that ALS patients had approximately twice
      as much galectin-3 as normal and disease controls. These results provide the
      proof of principle that biomarker identification in relevant and well-controlled
      animal models can be translated to human disease. The challenge is to validate
      our biomarker candidate proteins as true biomarkers for ALS that will be useful
      for diagnosis and/or monitoring disease activity in future clinical trials.

PMID- 20698587
TI  - Correlations between subsequent blinking events in single quantum dots.
AB  - We explain the long-range correlations found by Stefani and his co-workers
      between blinking times of single colloidal quantum dot emission. Our explanation
      is based on the multiple recombination center model we recently suggested. The
      model produces positive correlations between subsequent on--on and off--off times
      and negative on--off correlations, as observed in the experiment. We also
      reproduce qualitatively the dependence of correlations between subsequent on--on,
      on-off, and off--off times on the number of switching events separating them.

PMID- 20698588
TI  - Giant magnetoresistance observed in (Fe,Mn)3O4 artificial nanoconstrained
      structures at room temperature.
AB  - We fabricated ferromagnetic oxide (Fe,Mn)(3)O(4) (FMO) nanoconstrained structures
      using two different steps involving atomic force microscope lithography in
      combination with a pulsed laser deposition technique. The widths of three FMO
      nanoconstrained structures were 150, 100, and 50 nm. The I-V characteristic of
      the 50 nm width FMO nanoconstrained structure changed dramatically from linear to
      nonlinear after forming the nanoconstrained structure. The magnetoresistance also
      increased drastically from -0.2% to 150% at room temperature. These results
      indicate that well-defined complicated artificial transition metal oxide
      nanostructures allow the creation of huge spin response devices even at room
      temperature.

PMID- 20698589
TI  - Programmable growth of branched silicon nanowires using a focused ion beam.
AB  - Although significant progress has been made in being able to spatially define the
      position of material layers in vapor-liquid-solid (VLS) grown nanowires, less
      work has been carried out in deterministically defining the positions of nanowire
      branching points to facilitate more complicated structures beyond simple 1D
      wires. Work to date has focused on the growth of randomly branched nanowire
      structures. Here we develop a means for programmably designating nanowire
      branching points by means of focused ion beam-defined VLS catalytic points. This
      technique is repeatable without losing fidelity allowing multiple rounds of
      branching point definition followed by branch growth resulting in complex
      structures. The single crystal nature of this approach allows us to describe
      resulting structures with linear combinations of base vectors in three
      dimensional (3D) space. Finally, by etching the resulting 3D defined wire
      structures branched nanotubes were fabricated with interconnected nanochannels
      inside. We believe that the techniques developed here should comprise a useful
      tool for extending linear VLS nanowire growth to generalized 3D wire structures.

PMID- 20698590
TI  - Charge and spin state readout of a double quantum dot coupled to a resonator.
AB  - State readout is a key requirement for a quantum computer. For semiconductor
      based qubit devices it is usually accomplished using a separate mesoscopic
      electrometer. Here we demonstrate a simple detection scheme in which a radio
      frequency resonant circuit coupled to a semiconductor double quantum dot is used
      to probe its charge and spin states. These results demonstrate a new noninvasive
      technique for measuring charge and spin states in quantum dot systems without
      requiring a separate mesoscopic detector.

PMID- 20698591
TI  - Embedded binary eutectic alloy nanostructures: a new class of phase change
      materials.
AB  - Phase change materials are essential to a number of technologies ranging from
      optical data storage to energy storage and transport applications. This
      widespread interest has given rise to a substantial effort to develop bulk phase
      change materials well suited for desired applications. Here, we suggest a novel
      and complementary approach, the use of binary eutectic alloy nanoparticles
      embedded within a matrix. Using GeSn nanoparticles embedded in silica as an
      example, we establish that the presence of a nanoparticle/matrix interface
      enables one to stabilize both nanobicrystal and homogeneous alloy morphologies.
      Further, the kinetics of switching between the two morphologies can be tuned
      simply by altering the composition.

PMID- 20698592
TI  - LiMnPO4 nanoplate grown via solid-state reaction in molten hydrocarbon for Li-ion
      battery cathode.
AB  - Electrochemically active LiMnPO(4) nanoplates have been synthesized via a novel,
      single-step, solid-state reaction in molten hydrocarbon. The olivine-structured
      LiMnPO(4) nanoplates with a thickness of approximately 50 nm appear porous and
      were formed as nanocrystals were assembled and grew into nanorods along the [010]
      direction in the (100) plane. After carbon coating, the prepared LiMnPO(4)
      cathode demonstrated a flat potential at 4.1 V versus Li with a specific capacity
      reaching as high as 168 mAh/g under a galvanostatic charging/discharging mode,
      along with an excellent cyclability.

PMID- 20698593
TI  - Light induced charging of polymer functionalized nanorods.
AB  - ZnO nanorods were functionalized with new block copolymers containing a hole
      transporting moiety in one block and a dye and an anchor system in the second
      block. After functionalization, the ZnO nanorods are well dispersible in organic
      media and the fluorescence of the dye is quenched. Kelvin probe force microscopy
      was used to measure changes in electrical potential between the ZnO nanorod and
      the polymeric corona. Upon light irradiation, potential changes on the order of
      some tens of millivolts were observed on individual structures. This effect is
      attributed to light-induced charge separation between the ZnO nanorod and its
      hole transporting polymeric corona.

PMID- 20698594
TI  - In situ nanostructure generation and evolution within a bulk thermoelectric
      material to reduce lattice thermal conductivity.
AB  - We show experimentally the direct reduction in lattice thermal conductivity as a
      result of in situ nanostructure generation within a thermoelectric material.
      Solid solution alloys of the high-performance thermoelectric PbTe-PbS 8% can be
      synthesized through rapid cooling and subsequent high-temperature activation that
      induces a spontaneous nucleation and growth of PbS nanocrystals. The emergence of
      coherent PbS nanostructures reduces the lattice thermal conductivity from
      approximately 1 to approximately 0.4 W/mK between 400 and 500 K.

PMID- 20698595
TI  - Plasmon resonant cavities in vertical nanowire arrays.
AB  - We investigate tunable plasmon resonant cavity arrays in paired parallel nanowire
      waveguides. Resonances are observed when the waveguide length is an odd multiple
      of quarter plasmon wavelengths, consistent with boundary conditions of node and
      antinode at the ends. Two nanowire waveguides satisfy the dispersion relation of
      a planar metal-dielectric-metal waveguide of equivalent width equal to the square
      field average weighted gap. Confinement factors over 10(3) are possible due to
      plasmon focusing in the interwire space.

PMID- 20698596
TI  - Edge effects on the characteristics of li diffusion in graphene.
AB  - We study the adsorption and diffusion of Li atoms on the surface of planar
      graphenes by means of density functional theory. When the dimensionality of
      graphene is reduced to a quasi-one-dimension, armchair and zigzag edges appear.
      We show that the presence of these edges affects not only the reactivity of the
      carbon material toward the adsorption of Li adatoms but also their diffusion
      properties. These properties strongly depend on the specific morphology of the
      edges. Our results indicate that Li adatoms will diffuse toward the edges while
      Li diffusion channels appear along the ribbon axis. For most of the diffusion
      paths studied here, energy barriers are lower than those in graphene. This effect
      is significantly more pronounced toward the edges, where energy barriers can be
      up to 0.15 eV smaller than those in in graphene, producing an increase of up to 2
      orders of magnitude in the diffusion coefficient at room temperature. Our results
      indicate that electrodes fabricated with these materials should increase the
      power of Li-ion batteries.

PMID- 20698597
TI  - In vitro and in vivo studies of single-walled carbon nanohorns with encapsulated
      metallofullerenes and exohedrally functionalized quantum dots.
AB  - Single-walled carbon nanohorns (SWNHs) are new carbonaceous materials. In this
      paper, we report the first successful preparation of SWNHs encapsulating
      trimetallic nitride template endohedral metallofullerenes (TNT-EMFs). The
      resultant materials were functionalized by a high-speed vibration milling method
      and conjugated with CdSe/ZnS quantum dots (QDs). The successful encapsulation of
      TNT-EMFs and external functionalization with QDs provide a dual diagnostic
      platform for in vitro and in vivo biomedical applications of these new
      carbonaceous materials.

PMID- 20698598
TI  - Forster coupling in nanoparticle excitonic circuits.
AB  - Exciton transport in semiconductor nanoparticles underlies recent experiments on
      electrically controlled nanostructures and proposals for new artificial light
      harvesting systems. In this work, we develop a novel method for the numerical
      evaluation of the Forster matrix element, based on a three-dimensional real space
      grid and the self-consistent solution of the mesoscopic exciton in a macroscopic
      dielectric environment. This method enables the study of the role of the
      nanoparticle shape, spatially varying dielectric environments, and externally
      applied electric fields. Depending on the orientation of the transition dipole,
      the Forster coupling is shown to be either increased or decreased as a function
      of the nanoparticle shape and of the properties of the dielectric environment. In
      the presence of an electric field, we investigate the relation between excitonic
      binding and confinement effects. We also study a type II core-shell quantum dot
      where electron and hole are spatially separated due to a particular configuration
      of the bandstructure.

PMID- 20698599
TI  - Epitaxial heterostructures of ultrathin topological insulator nanoplate and
      graphene.
AB  - The authors present a van der Waals epitaxy of high-quality ultrathin nanoplates
      of topological insulator Bi(2)Se(3) on a pristine graphene substrate using a
      simple vapor-phase deposition method. Sub-10-nm-thick nanoplates of layered
      Bi(2)Se(3) with defined orientations can be epitaxially grown on a few-layer
      pristine graphene substrate. We show the evolution of Raman spectra with the
      number of Bi(2)Se(3) layers on few-layer graphene. Bi(2)Se(3) nanoplates with a
      thickness of three quintuple-layers (3-QL) exhibit the strongest Raman intensity.
      Strain effects in the Bi(2)Se(3)/graphene nanoplate heterostructures is also
      studied by Raman spectroscopy. 1-QL and 2-QL Bi(2)Se(3) nanoplates experience
      tensile stress, consistent with compressive stress in single-layer and bilayer
      graphene substrates. Our results suggest an approach for the synthesis of
      epitaxial heterostructures that consist of an ultrathin topological insulator and
      graphene, which may be a new direction for electronic and spintronic
      applications.

PMID- 20698600
TI  - Novel streptavidin-functionalized silicon nanowire arrays for CD4+ T lymphocyte
      separation.
AB  - Silicon nanowires (SiNWs) offer promising inorganic nanostructures for biomedical
      application. Here, we report the development of a novel SiNW array designed for
      isolating primary CD4(+) T lymphocytes from the heterogeneous mixture of cell
      populations. Our system employed the specific high-affinity binding features of
      streptavidin (STR)-functionalized SiNW with biotin-labeled CD4(+) T lymphocytes.
      Fabricated SiNW arrays easily separated the CD4(+) T lymphocytes from the mouse
      whole splenocytes with over approximately 88% purity and demonstrated tight
      attachment to CD4(+) T lymphocytes by scanning electron microscopy. Thus, our STR
      SiNW arrays provide a potential tool for specific cell separation and further
      present a possibility to be applied to the other area of biomedical applications.

PMID- 20698601
TI  - Low voltage nanoelectromechanical switches based on silicon carbide nanowires.
AB  - We report experimental demonstrations of electrostatically actuated, contact-mode
      nanoelectromechanical switches based on very thin silicon carbide (SiC) nanowires
      (NWs). These NWs are lithographically patterned from a 50 nm thick SiC layer
      heteroepitaxially grown on single-crystal silicon (Si). Several generic designs
      of in-plane electrostatic SiC NW switches have been realized, with NW widths as
      small as approximately 20 nm and lateral switching gaps as narrow as
      approximately 10 nm. Very low switch-on voltages are obtained, from a few volts
      down to approximately 1 V level. Two-terminal, contact-mode "hot" switching with
      high on/off ratios (>10(2) or 10(3)) has been demonstrated repeatedly for many
      devices. We find enhanced switching performance in bare SiC NWs, with lifetimes
      exceeding those based on metallized SiC NWs.

PMID- 20698602
TI  - Crossed-nanowire molecular junctions: a new multispectroscopy platform for
      conduction--structure correlations.
AB  - We report a crossed-nanowire molecular junction array platform that enables
      direct measurement of current-voltage-temperature characteristics simultaneously
      with inelastic electron tunneling and Raman vibrational spectra on the same
      junction. Measurements on dithiol-terminated oligo(phenylene-ethynylene)
      junctions show both spectroscopies interrogate the gap-confined molecules to
      reveal distinct molecular features. This versatile platform allows investigation
      of advanced phenomena such as molecular switching and cooperative effects with
      the flexible ability to scale both the junction geometries and array sizes.

PMID- 20698603
TI  - Transport, separation, and accumulation of proteins on supported lipid bilayers.
AB  - Transport, separation, and accumulation of proteins in their natural environment
      are central goals in protein biotechnology. Miniaturized assays of supported
      lipid bilayers (SLBs) have been proposed as promising candidates to realize such
      technology on a chip, but a modular system for the controlled transport of
      membrane proteins does not exist. In this letter, we demonstrate that standing
      surface acoustic waves drive the in-plane redistribution of proteins on planar
      SLBs over macroscopic distances (3.5 mm). Accumulation of proteins in periodic
      patterns of about 10-fold protein concentration difference is accomplished and
      shown to relax into the homogeneous state by diffusion. Different proteins
      separate in individual fractions from a homogeneous distribution and are
      transported and accumulated into clusters using beats. The modular planar setup
      has the potential of integrating other lab-on-a-chip tools, for monitoring the
      membrane-protein integrity or adding microfluidic features for blood screening or
      DNA analysis.

PMID- 20698604
TI  - DNA translocation through graphene nanopores.
AB  - We report on DNA translocations through nanopores created in graphene membranes.
      Devices consist of 1-5 nm thick graphene membranes with electron-beam sculpted
      nanopores from 5 to 10 nm in diameter. Due to the thin nature of the graphene
      membranes, we observe larger blocked currents than for traditional solid-state
      nanopores. However, ionic current noise levels are several orders of magnitude
      larger than those for silicon nitride nanopores. These fluctuations are reduced
      with the atomic-layer deposition of 5 nm of titanium dioxide over the device.
      Unlike traditional solid-state nanopore materials that are insulating, graphene
      is an excellent electrical conductor. Use of graphene as a membrane material
      opens the door to a new class of nanopore devices in which electronic sensing and
      control are performed directly at the pore.

PMID- 20698605
TI  - Efficient directional coupling between silicon and copper plasmonic nanoslot
      waveguides: toward metal-oxide-silicon nanophotonics.
AB  - Coupling plasmonics and silicon photonics is the best way to bridge the size gap
      between macroscopic optics and nanodevices in general and especially
      nanoelectronic devices. We report on the realization of key blocks for future
      plasmonic planar integrated optics, nano-optical couplers, and nanoslot
      waveguides that are compatible both with the silicon photonics and the CMOS
      microelectronics. Copper-based devices provide for very efficient optical
      coupling, unexpectedly low propagation losses and a broadband sub-50 nm optical
      confinement. The fabrication in a standard frontline microelectronic facilities
      hints broad possibilities of hybrid opto-electronic very large scale integration.

PMID- 20698606
TI  - Double-gate nanowire field effect transistor for a biosensor.
AB  - A silicon nanowire field effect transistor (FET) straddled by the double-gate was
      demonstrated for biosensor application. The separated double-gates, G1 (primary)
      and G2 (secondary), allow independent voltage control to modulate channel
      potential. Therefore, the detection sensitivity was enhanced by the use of G2. By
      applying weakly positive bias to G2, the sensing window was significantly
      broadened compared to the case of employing G1 only, which is nominally used in
      conventional nanowire FET-based biosensors. The charge effect arising from
      biomolecules was also analyzed. Double-gate nanowire FET can pave the way for an
      electrically working biosensor without a labeling process.

PMID- 20698607
TI  - Nanopatterned metallic films for use as transparent conductive electrodes in
      optoelectronic devices.
AB  - We investigate the use of nanopatterned metallic films as transparent conductive
      electrodes in optoelectronic devices. We find that the physics of nanopatterned
      electrodes, which are often optically thin metallic films, differs from that of
      optically thick metallic films. We analyze the optical properties when performing
      a geometrical transformation that maintains the electrical properties. For one
      dimensional patterns of metallic wires, the analysis favors tall and narrow
      wires. Our design principles remain valid for oblique incidence and readily carry
      over to two-dimensional patterns.

PMID- 20698608
TI  - Site selective inelastic electron tunneling spectroscopy probed by isotope
      labeling.
AB  - We study inelastic scattering in alkanethiol self-assembled monolayers using
      isotope labeling and unambiguously determine which molecular vibrations are
      active in the inelastic electron tunneling spectroscopy. The selective
      deuteration of the molecule also allows us to show that the different parts of
      the molecule contribute approximately equally to inelastic signal. Our first
      principles calculations confirm the experimental results and provide insights on
      electron transport through molecules.

PMID- 20698609
TI  - Strong and tunable spin--orbit coupling of one-dimensional holes in Ge/Si
      core/shell nanowires.
AB  - We investigate the low-temperature magneto-transport properties of individual
      Ge/Si core/shell nanowires. Negative magneto-conductance was observed, which is a
      signature of one-dimensional weak antilocalization of holes in the presence of
      strong spin--orbit coupling. The temperature and back gate dependences of phase
      coherence length, spin--orbit relaxation time, and background conductance were
      studied. Specifically, we show that the spin--orbit coupling strength can be
      modulated by more than five folds with an external electric field. These results
      suggest the Ge/Si nanowire system possesses strong and tunable spin--orbit
      interactions and may serve as a candidate for spintronics applications.

PMID- 20698610
TI  - Nanoscale optical detector with single-photon and multiphoton sensitivity.
AB  - We present the first nanoscale (down to approximately 50 x 50 nm(2)) detector
      displaying single-photon sensitivity and a nanosecond response. This type of
      nanodetector can also be operated in multiphoton mode, where the detection
      threshold can be set at N = 1, 2, 3, or 4 photons, thus allowing the mapping of
      photon number statistics on the nanoscale. Its operation principle based on that
      of hot-spot formation in superconducting nanowires allies the temporal resolution
      and sensitivity of superconducting single-photon detectors with subwavelength
      resolution and photon number discrimination. Such detectors can be of great
      interest for the study of nanophotonic devices at low temperature.

PMID- 20698611
TI  - On the correlation between nanoscale structure and magnetic properties in ordered
      mesoporous cobalt ferrite (CoFe2O4) thin films.
AB  - In this work, we report the synthesis of periodic nanoporous cobalt ferrite (CFO)
      that exhibits tunable room temperature ferrimagnetism. The porous cubic CFO
      frameworks are fabricated by coassembly of inorganic precursors with a large
      amphiphilic diblock copolymer, referred to as KLE. The inverse spinel framework
      boasts an ordered open network of pores averaging 14 nm in diameter. The domain
      sizes of the crystallites are tunable from 6 to 15 nm, a control which comes at
      little cost to the ordering of the mesostructure. Increases in crystalline domain
      size directly correlate with increases in room temperature coercivity. In
      addition, these materials show a strong preference for out-of-plane oriented
      magnetization, which is unique in a thin film system. The preference is explained
      by in-plane tensile strain, combined with relaxation of the out-of-plane strain
      through flexing of the mesopores. It is envisioned that the pores of this
      ferrimagnet could facilitate the formation of a diverse range of exchange coupled
      composite materials.

PMID- 20698612
TI  - Fast and scalable printing of large area monolayer nanoparticles for
      nanotexturing applications.
AB  - Recently, there have been several studies demonstrating that highly ordered
      nanoscale texturing can dramatically increase performance of applications such as
      light absorption in thin-film solar cells. However, those methods used to make
      the nanostructures are not compatible with large-scale fabrication. Here we
      demonstrate that a technique currently used in roll-to-roll processing to deposit
      uniform thin films from solution, a wire-wound rod coating method, can be adapted
      to deposit close-packed monolayers or multilayers of silica nanoparticles on a
      variety of rigid and flexible substrates. Amorphous silicon thin films deposited
      on these nanoparticle monolayers exhibit 42% higher absorption over the
      integrated AM 1.5 spectrum than the planar controls. This simple assembly
      technique can be used to improve solar cells, fuel cells, light emitting diodes
      and other devices where ordered nanoscale texturing is critical for optimal
      performance.

PMID- 20698613
TI  - Properties of fluorinated graphene films.
AB  - Graphene films grown on Cu foils have been fluorinated with xenon difluoride
      (XeF(2)) gas on one or both sides. When exposed on one side the F coverage
      saturates at 25% (C(4)F), which is optically transparent, over 6 orders of
      magnitude more resistive than graphene, and readily patterned. Density functional
      calculations for varying coverages indicate that a C(4)F configuration is lowest
      in energy and that the calculated band gap increases with increasing coverage,
      becoming 2.93 eV for one C(4)F configuration. During defluorination, we find
      hydrazine treatment effectively removes fluorine while retaining graphene's
      carbon skeleton. The same films may be fluorinated on both sides by transferring
      graphene to a silicon-on-insulator substrate enabling XeF(2) gas to etch the Si
      underlayer and fluorinate the backside of the graphene film to form
      perfluorographane (CF) for which calculated the band gap is 3.07 eV. Our results
      indicate single-side fluorination provides the necessary electronic and optical
      changes to be practical for graphene device applications.

PMID- 20698614
TI  - Plasmonic response of nanoscale spirals.
AB  - The Archimedean spiral geometry presents a platform for exploration of complex
      plasmonic mechanisms and applications. Here we show both through simulations and
      experiment that more complex plasmonic modes with unique near-field structure and
      larger mode volumes can be realized within a single, topologically robust
      structure. In the spiral, complex polarization response, resonant interactions
      and symmetry-breaking features are defined by the width and spacing of the spiral
      tracks and by the winding number of the spiral.

PMID- 20698615
TI  - Comparing multiple exciton generation in quantum dots to impact ionization in
      bulk semiconductors: implications for enhancement of solar energy conversion.
AB  - Multiple exciton generation (MEG) in quantum dots (QDs) and impact ionization
      (II) in bulk semiconductors are processes that describe producing more than one
      electron-hole pair per absorbed photon. We derive expressions for the proper way
      to compare MEG in QDs with II in bulk semiconductors and argue that there are
      important differences in the photophysics between bulk semiconductors and QDs.
      Our analysis demonstrates that the fundamental unit of energy required to produce
      each electron-hole pair in a given QD is the band gap energy. We find that the
      efficiency of the multiplication process increases by at least 2 in PbSe QDs
      compared to bulk PbSe, while the competition between cooling and multiplication
      favors multiplication by a factor of 3 in QDs. We also demonstrate that power
      conversion efficiencies in QD solar cells exhibiting MEG can greatly exceed
      conversion efficiencies of their bulk counterparts, especially if the MEG
      threshold energy can be reduced toward twice the QD band gap energy, which
      requires a further increase in the MEG efficiency. Finally, we discuss the
      research challenges associated with achieving the maximum benefit of MEG in solar
      energy conversion since we show the threshold and efficiency are mathematically
      related.

PMID- 20698616
TI  - Epitaxial CdSe-Au nanocrystal heterostructures by thermal annealing.
AB  - The thermal evolution of a collection of heterogeneous CdSe-Au nanosystems (Au
      decorated CdSe nanorods, networks, vertical assemblies) prepared by wet-chemical
      approaches was monitored in situ in the transmission electron microscope. In
      contrast to interfaces that are formed during kinetically controlled wet chemical
      synthesis, heating under vacuum conditions results in distinct and well-defined
      CdSe/Au interfaces, located at the CdSe polar surfaces. The high quality of these
      interfaces should make the heterostructures more suitable for use in nanoscale
      electronic devices.

PMID- 20698617
TI  - Diameter dependence of the transport properties of antimony telluride nanowires.
AB  - We report measurements of electronic, thermoelectric, and galvanomagnetic
      properties of individual single crystal antimony telluride (Sb(2)Te(3)) nanowires
      with diameters in the range of 20-100 nm. Temperature-dependent resistivity and
      thermoelectric power (TEP) measurements indicate hole dominant diffusive
      thermoelectric generation with an enhancement of the TEP for smaller diameter
      wires up to 110 microV/K at T = 300 K. We measure the magnetoresistance in
      magnetic fields both parallel and perpendicular to the nanowire [110] axis, where
      strong anisotropic positive magnetoresistance behavior was observed.

PMID- 20698618
TI  - Supported ru-pt bimetallic nanoparticle catalysts prepared by atomic layer
      deposition.
AB  - Atomic layer deposition (ALD) is used to deposit ruthenium-platinum
      nanostructured catalysts using 2,4-(dimethylpentadienyl)(ethylcyclopentadienyl)
      ruthenium, trimethyl(methylcyclopentadienyl) platinum, and oxygen as precursors.
      Transmission electron microscopy shows discrete 1.2 nm nanoparticles decorating
      the surface of the spherical alumina support. The Ru-Pt particles are crystalline
      and have a crystal structure similar to pure platinum. X-ray fluorescence
      measurements show that the nanoparticle composition is controlled by the ratio of
      metal precursor ALD cycles. X-ray absorption spectroscopy at the Ru K-edge
      indicates a nearest neighbor Ru-Pt interaction consistent with a bimetallic
      composition. Methanol decomposition reactions further confirm a Ru-Pt interaction
      and show enhanced methanol conversion for the bimetallic nanoparticles when
      compared to catalysts comprised of a mixture of pure Pt and Ru nanoparticles of
      similar loading. These results demonstrate that ALD is a viable technique for
      synthesizing mixed-metal nanostructures suitable for catalysis and other
      applications.

PMID- 20698619
TI  - Band alignment tailoring of InAs1-xSbx/GaAs quantum dots: control of type I to
      type II transition.
AB  - We report the growth of InAs(1-x)Sb(x) self-assembled quantum dots (QDs) on GaAs
      (100) by molecular beam epitaxy. The optical properties of the QDs are
      investigated by photoluminescence (PL) and time-resolved photoluminescence
      (TRPL). A type I to type II band alignment transition is demonstrated by both
      power-dependent PL and TRPL in InAs(1-x)Sb(x) QD samples with increased Sb beam
      flux. Results are compared to an eight-band strain-dependent k x p model
      incorporating detailed QD structure and alloy composition. The calculations show
      that the conduction band offset of InAs(1-x)Sb(x)/GaAs can be continuously tuned
      from 0 to 500 meV and a flat conduction band alignment exists when 60% Sb is
      incorporated into the QDs. Our study offers the possibility of tailoring the band
      structure of GaAs based InAsSb QDs and opens up new means for device
      applications.

PMID- 20698620
TI  - Vibrational energy transport through a capping layer of appropriately designed
      peptide helices over gold nanoparticles.
AB  - We design and characterize spherical gold nanoparticles, which are covalently
      linked to and completely covered by 3(10)-helical peptides. These helices provide
      a scaffold to place (13)C=O isotope labels at defined distances from the gold
      surface, which we employ as local thermometers. Probing these reporter groups
      with transient infrared spectroscopy, we monitor the vibrational energy flow
      across the peptide capping layer following excitation of the nanoparticle plasmon
      resonance.

PMID- 20698621
TI  - Piezopotential gated nanowire--nanotube hybrid field-effect transistor.
AB  - We report the first piezoelectric potential gated hybrid field-effect transistors
      based on nanotubes and nanowires. The device consists of single-walled carbon
      nanotubes (SWNTs) on the bottom and crossed ZnO piezoelectric fine wire (PFW) on
      the top with an insulating layer between. Here, SWNTs serve as a carrier
      transport channel, and a single-crystal ZnO PFW acts as the power-free, contact
      free gate or even an energy-harvesting component later on. The piezopotential
      created by an external force in the ZnO PFW is demonstrated to control the charge
      transport in the SWNT channel located underneath. The magnitude of the
      piezopotential in the PFW at a tensile strain of 0.05% is measured to be 0.4-0.6
      V. The device is a unique coupling between the piezoelectric property of the ZnO
      PFW and the semiconductor performance of the SWNT with a full utilization of its
      mobility. The newly demonstrated device has potential applications as a strain
      sensor, force/pressure monitor, security trigger, and analog-signal touch screen.

PMID- 20698622
TI  - Optical spectroscopy of conductive junctions in plasmonic cavities.
AB  - The optical properties of a nanoparticle dimer bridged by a conductive junction
      depend strongly on the junction conductivity. As the conductivity increases, the
      bonding dimer plasmon blueshifts and broadens. For large conductance, a low
      energy charge transfer plasmon also appears in the spectra with a line width that
      decreases with increasing conductance. A simple physical model for the
      understanding of the spectral feature is presented. Our finding of a strong
      influence of junction conductivity on the optical spectrum suggests that
      plasmonic cavities might serve as probes of molecular conductance at elevated
      frequencies not accessible through electrical measurements.

PMID- 20698623
TI  - Protein--nanoparticle interaction: identification of the ubiquitin--gold
      nanoparticle interaction site.
AB  - We demonstrate that it is possible to identify the protein--nanoparticle
      interaction site at amino acid scale in solution. Using NMR, chemical shift
      perturbation analysis, and dynamic light scattering we have identified a specific
      domain of human ubiquitin that interacts with gold nanoparticles. This method
      allows a detailed structural analysis of proteins absorbed onto surfaces of
      nanoparticles in physiological conditions and it will provide much needed
      experimental data for better modeling and prediction of protein--nanoparticle
      interactions.

PMID- 20698624
TI  - A DNA--silver nanocluster probe that fluoresces upon hybridization.
AB  - DNA-templated silver nanoclusters (DNA/Ag NCs) are an emerging set of
      fluorophores that are smaller than semiconductor quantum dots and can have better
      photostability and brightness than commonly used organic dyes. Here we find the
      red fluorescence of DNA/Ag NCs can be enhanced 500-fold when placed in proximity
      to guanine-rich DNA sequences. On the basis of this new phenomenon, we have
      designed a DNA detection probe (NanoCluster Beacon, NCB) that "lights up" upon
      target binding. Since NCBs do not rely on Forster energy transfer for quenching,
      they can easily reach high (>100) signal-to-background ratios (S/B ratios) upon
      target binding. Here, in a separation-free assay, we demonstrate NCB detection of
      an influenza target with a S/B ratio of 175, a factor of 5 better than a
      conventional molecular beacon probe. Since the observed fluorescence enhancement
      is caused by intrinsic nucleobases, our detection technique is simple,
      inexpensive, and compatible with commercial DNA synthesizers.

PMID- 20698625
TI  - Ultrathin topological insulator Bi2Se3 nanoribbons exfoliated by atomic force
      microscopy.
AB  - Ultrathin topological insulator nanostructures, in which coupling between top and
      bottom surface states takes place, are of great intellectual and practical
      importance. Due to the weak van der Waals interaction between adjacent quintuple
      layers (QLs), the layered bismuth selenide (Bi(2)Se(3)), a single Dirac-cone
      topological insulator with a large bulk gap, can be exfoliated down to a few QLs.
      In this paper, we report the first controlled mechanical exfoliation of
      Bi(2)Se(3) nanoribbons (>50 QLs) by an atomic force microscope (AFM) tip down to
      a single QL. Microwave impedance microscopy is employed to map out the local
      conductivity of such ultrathin nanoribbons, showing drastic difference in sheet
      resistance between 1-2 QLs and 4-5 QLs. Transport measurement carried out on an
      exfoliated (<or=5 QLs) Bi(2)Se(3) device shows nonmetallic temperature dependence
      of resistance, in sharp contrast to the metallic behavior seen in thick (>50 QLs)
      ribbons. These AFM-exfoliated thin nanoribbons afford interesting candidates for
      studying the transition from quantum spin Hall surface to edge states.

PMID- 20698626
TI  - Extraordinary optical transmission enhanced by nanofocusing.
AB  - We demonstrate that the phenomenon of extraordinary optical transmission (EOT)
      through perforated metal films can be further boosted up by utilizing
      nanofocusing of radiation in tapered slits. For one-dimensional arrays of tapered
      slits in optically thick suspended gold films, we show that the maximum
      transmission at resonance is achieved for taper angles in the range of 7-10
      degrees increasing significantly in comparison with the transmission by straight
      slits. Transmission spectroscopy of fabricated 500 and 700 nm period tapered
      slits in a 180 nm thick gold film on a glass substrate demonstrates the enhanced
      EOT with the resonance transmission being as high as approximately 0.18 for the
      filling ratio of approximately 0.13 and showing good correspondence with
      theoretical results. It is also shown that the enhanced transmission can be
      achieved with either weak (2.5%) or strong (43%) reflection depending on the
      direction of light (normal) incidence.

PMID- 20698627
TI  - Resonance energy transfer and superradiance mediated by plasmonic nanowaveguides.
AB  - We show how both the subwavelength confinement associated with surface plasmons
      and the one-dimensional character of plasmonic waveguides can be exploited to
      enhance the coupling between quantum emitters. Resonance energy transfer and the
      phenomenon of superradiance are investigated in three different waveguiding
      schemes (wires, wedges, and channels) by means of the Finite Element Method. We
      also develop a simplified model that is able to capture the main features of the
      numerical results.

PMID- 20698628
TI  - Maximized optical absorption in ultrathin films and its application to plasmon
      based two-dimensional photovoltaics.
AB  - For ultrathin films of a given material, light absorption is proportional to the
      film thickness. However, if the optical constants of the film are chosen in an
      optimal way, light absorption can be high even for extremely thin films and
      optical path length. We derive the optimal conditions and show how the maximized
      absorptance depends on film thickness. It is then shown that the optimal
      situation can be emulated by tuning of the geometric parameters in feasible
      nanocomposites combining plasmonic materials with semiconductors. Useful design
      criteria and estimates for the spatial absorption-distribution over the composite
      materials are provided. On the basis of efficient exchange of oscillator strength
      between the plasmonic and semiconductor constituents, a high quantum yield for
      semiconductor absorption can be achieved. The results are far-reaching with
      particularly promising opportunities for plasmonic solar cells.

PMID- 20698629
TI  - Suppression of biexciton auger recombination in CdSe/CdS dot/rods: role of the
      electronic structure in the carrier dynamics.
AB  - We studied carrier dynamics in semiconductor nanocrystals consisting of a small
      CdSe dot embedded in an elongated, rod-shaped CdS shell, using the ultrafast pump
      probe technique. We found clear evidence of a substantial suppression of the
      Auger nonradiative recombination in the biexciton regime. Moreover, a simple
      model of the dynamics in which biexcitons show no Auger recombination, and only
      holes are localized in the dot, fits well the differential transmission observed
      at all pump densities. The long biexciton lifetime results into an observed long
      living gain having a peak that is red shifted with respect to the lowest energy
      absorption peak. We argue that the origin of the large relative gain observed at
      large fillings is related to the peculiar structure of the electronic levels, and
      in particular, to delocalization of electrons in the rod.

PMID- 20698630
TI  - Flexible high-output nanogenerator based on lateral ZnO nanowire array.
AB  - We report here a simple and effective approach, named scalable sweeping-printing
      method, for fabricating flexible high-output nanogenerator (HONG) that can
      effectively harvesting mechanical energy for driving a small commercial
      electronic component. The technique consists of two main steps. In the first
      step, the vertically aligned ZnO nanowires (NWs) are transferred to a receiving
      substrate to form horizontally aligned arrays. Then, parallel stripe type of
      electrodes are deposited to connect all of the NWs together. Using a single layer
      of HONG structure, an open-circuit voltage of up to 2.03 V and a peak output
      power density of approximately 11 mW/cm(3) have been achieved. The generated
      electric energy was effectively stored by utilizing capacitors, and it was
      successfully used to light up a commercial light-emitting diode (LED), which is a
      landmark progress toward building self-powered devices by harvesting energy from
      the environment. This research opens up the path for practical applications of
      nanowire-based piezoelectric nanogeneragtors for self-powered nanosystems.

PMID- 20698631
TI  - Strain-induced band gap modification in coherent core/shell nanostructures.
AB  - Using first-principles calculations within density functional theory, we study
      the relative impacts of quantum confinement and strain on the electronic
      structure of two II-VI semiconductor compounds with a large lattice-mismatch,
      CdSe and CdTe, in core/shell nanowire geometries with different core radii and
      shell thicknesses. For fixed CdSe core radius, we find that the electronic band
      gap in the core is significantly reduced with increasing CdTe shell thickness, by
      an amount comparable to that expected from quantum confinement, due to the
      development of a large and highly anisotropic strain throughout the
      heterostructure. A straightforward analysis allows us to separate quantitatively
      changes in band gap due to quantum confinement and strain. Our studies elucidate
      and quantify the importance of strain in determining the electronic and optical
      properties of core/shell nanostructures.

PMID- 20698632
TI  - Chip-scale nanofabrication of single spins and spin arrays in diamond.
AB  - We demonstrate a technique to nanofabricate nitrogen vacancy (NV) centers in
      diamond based on broad-beam nitrogen implantation through apertures in electron
      beam lithography resist. This method enables high-throughput nanofabrication of
      single NV centers on sub-100-nm length scales. Secondary ion mass spectroscopy
      measurements facilitate depth profiling of the implanted nitrogen to provide
      three-dimensional characterization of the NV center spatial distribution.
      Measurements of NV center coherence with on-chip coplanar waveguides suggest a
      pathway for incorporating this scalable nanofabrication technique in future
      quantum applications.

PMID- 20698633
TI  - Enhanced optical transmission mediated by localized plasmons in anisotropic,
      three-dimensional nanohole arrays.
AB  - This paper describes three-dimensional (3D) nanohole arrays whose high optical
      transmission is mediated more by localized surface plasmon (LSP) excitations than
      by surface plasmon polaritons (SPPs). First, LSPs on 3D hole arrays lead to
      optical transmission an order of magnitude higher than 2D planar hole arrays.
      Second, LSP-mediated transmission is broadband and more tunable than SPP-enhanced
      transmission, which is restricted by Bragg coupling. Third, for the first time,
      two types of surface plasmons can be selectively excited and manipulated on the
      same plasmonic substrate. This new plasmonic substrate fabricated by high
      throughput nanolithography techniques paves the way for cutting-edge
      optoelectronic and biomedical applications.

PMID- 20698634
TI  - Frequency domain detection of biomolecules using silicon nanowire biosensors.
AB  - We demonstrate a new protein detection methodology based upon frequency domain
      electrical measurement using silicon nanowire field-effect transistor (SiNW FET)
      biosensors. The power spectral density of voltage from a current-biased SiNW FET
      shows 1/f-dependence in frequency domain for measurements of antibody
      functionalized SiNW devices in buffer solution or in the presence of protein not
      specific to the antibody receptor. In the presence of protein (antigen)
      recognized specifically by the antibody-functionalized SiNW FET, the frequency
      spectrum exhibits a Lorentzian shape with a characteristic frequency of several
      kilohertz. Frequency and conventional time domain measurements carried out with
      the same device as a function of antigen concentration show more than 10-fold
      increase in detection sensitivity in the frequency domain data. These
      concentration-dependent results together with studies of antibody receptor
      density effect further address possible origins of the Lorentzian frequency
      spectrum. Our results show that frequency domain measurements can be used as a
      complementary approach to conventional time domain measurements for
      ultrasensitive electrical detection of proteins and other biomolecules using
      nanoscale FETs.

PMID- 20698635
TI  - Fano resonances in plasmonic nanoclusters: geometrical and chemical tunability.
AB  - Clusters of plasmonic nanoparticles and nanostructures support Fano resonances.
      Here we show that this spectral feature, produced by the interference between
      bright and dark modes of the nanoparticle cluster, is strongly dependent upon
      both geometry and local dielectric environment. This permits a highly sensitive
      tunability of the Fano dip in both wavelength and amplitude by varying cluster
      dimensions, geometry, and relative size of the individual nanocluster components.
      Plasmonic nanoclusters show an unprecedented sensitivity to dielectric
      environment with a local surface plasmon resonance figure of merit of 5.7, the
      highest yet reported for localized surface plasmon resonance sensing in a finite
      nanostructure.

PMID- 20698636
TI  - Nonchaotic nonlinear motion visualized in complex nanostructures by stereographic
      4D electron microscopy.
AB  - Direct electron imaging with sufficient time resolution is a powerful tool for
      visualizing the three-dimensional (3D) mechanical motion and resolving the four
      dimensional (4D) trajectories of many different components of a nanomachine,
      e.g., a NEMS device. Here, we report a nanoscale nonchaotic motion of a nano- and
      microstructured NiTi shape memory alloy in 4D electron microscopy. A huge
      amplitude oscillatory mechanical motion following laser heating is observed
      repetitively, likened to a 3D motion of a conductor's baton. By time-resolved 4D
      stereographic reconstruction of the motion, prominent vibrational frequencies
      (3.0, 3.8, 6.8, and 14.5 MHz) are fully characterized, showing evidence of
      nonlinear behavior. Moreover, it is found that a stress (fluence)--strain
      (displacement) profile shows nonlinear elasticity. The observed resonances of the
      nanostructure are reminiscent of classical molecular quasi-periodic behavior, but
      here both the amplitude and frequency of the motion are visualized using
      ultrafast electron microscopy.

PMID- 20698637
TI  - Metastable dark States enable ground state depletion microscopy of nitrogen
      vacancy centers in diamond with diffraction-unlimited resolution.
AB  - Current far-field optical nanoscopy schemes overcome the diffraction barrier by
      ensuring that adjacent features assume different states upon detection. Ideally,
      the transition between these states can be repeated endlessly and, if performed
      optically, with low levels of light. Here we report such optical switching,
      realized by pairing the luminescent triplet and a long-lived dark state of
      diamond color centers, enabling their imaging with a resolution >10 times beyond
      the diffraction barrier (<20 nm).

PMID- 20698638
TI  - Anomalous piezoresistance effect in ultrastrained silicon nanowires.
AB  - In this paper we demonstrate that under ultrahigh strain conditions p-type single
      crystal silicon nanowires possess an anomalous piezoresistance effect. The
      measurements were performed on vapor-liquid-solid (VLS) grown Si nanowires,
      monolithically integrated in a microelectro-mechanical loading module. The
      special setup enables the application of pure uniaxial tensile strain along the
      <111> growth direction of individual, 100 nm thick Si nanowires while
      simultaneously measuring the resistance of the nanowires. For low strain levels
      (nanowire elongation less than 0.8%), our measurements revealed the expected
      positive piezoresistance effect, whereas for ultrahigh strain levels a transition
      to anomalous negative piezoresistance was observed. For the maximum tensile
      strain of 3.5%, the resistance of the Si nanowires decreased by a factor of 10.
      Even at these high strain amplitudes, no fatigue failures are observed for
      several hundred loading cycles. The ability to fabricate single-crystal nanowires
      that are widely free of structural defects will it make possible to apply high
      strain without fracturing to other materials as well, therefore in any
      application where crystallinity and strain are important, the idea of making
      nanowires should be of a high value.

PMID- 20698639
TI  - Large scale growth and characterization of atomic hexagonal boron nitride layers.
AB  - Hexagonal boron nitride (h-BN), a layered material similar to graphite, is a
      promising dielectric. Monolayer h-BN, so-called "white graphene", has been
      isolated from bulk BN and could be useful as a complementary two-dimensional
      dielectric substrate for graphene electronics. Here we report the large area
      synthesis of h-BN films consisting of two to five atomic layers, using chemical
      vapor deposition. These atomic films show a large optical energy band gap of 5.5
      eV and are highly transparent over a broad wavelength range. The mechanical
      properties of the h-BN films, measured by nanoindentation, show 2D elastic
      modulus in the range of 200-500 N/m, which is corroborated by corresponding
      theoretical calculations.

PMID- 20698640
TI  - Self-assembled ferrimagnet--polymer composites for magnetic recording media.
AB  - A self-assembled magnetic recording medium was created using colloidal
      ferrimagnetic building blocks. Monodisperse cobalt ferrite nanoparticles
      (CoFe(2)O(4)) were synthesized using solution-based methods and then stabilized
      in solution using the amphiphilic diblock copolymer, poly(acrylic acid)-b
      poly(styrene) (PAA-PS). The acid groups of the acrylate block bound the polymer
      to the nanoparticle surface via multivalent interactions, while the styrene block
      afforded the magnetic nanoparticle--polymer complex solubility in organic
      solvents. Moreover, the diblock copolymer improved the colloidal stability of the
      ferrimagnetic CoFe(2)O(4) nanoparticles by reducing the strong interparticle
      magnetic interactions, which typically caused the ferrimagnetic nanoparticles to
      irreversibly aggregate. The nanoparticle--polymer complex was spin-coated onto a
      silicon substrate to afford self-organized thin film arrays, with the
      interparticle spacing determined by the molecular weight of the diblock
      copolymer. The thin film composite was also exposed to an external magnetic field
      while simultaneously heated above the glass transition temperature of
      poly(styrene) to allow the nanoparticles to physically rotate to align their easy
      axes with the direction of the magnetic field. In order to demonstrate that this
      self-assembled ferrimagnet--polymer composite was suitable as a magnetic
      recording media, read/write cycles were demonstrated using a contact magnetic
      tester. This work provides a simple route to synthesizing stabilized
      ferrimagnetic nanocrystals that are suitable for developing magnetic recording
      media.

PMID- 20698642
TI  - Magic angle spinning NMR investigation of influenza A M2(18-60): support for an
      allosteric mechanism of inhibition.
AB  - The tetrameric M2 proton channel from influenza A virus conducts protons at low
      pH and is inhibited by aminoadamantyl drugs such as amantadine and rimantadine
      (Rmt). We report magic angle spinning NMR spectra of POPC and DPhPC membrane
      embedded M2(18-60), both apo and in the presence of Rmt. Similar line widths in
      the spectra of apo and bound M2 indicate that Rmt does not have a significant
      impact on the dynamics or conformational heterogeneity of this construct.
      Substantial chemical shift changes for many residues in the transmembrane region
      support an allosteric mechanism of inhibition. An Rmt titration supports a
      binding stoichiometry of >1 Rmt molecule per channel and shows that nonspecific
      binding or changes in membrane composition are unlikely sources of the chemical
      shift changes. In addition, doubling of spectral lines in all of the observed
      samples provides evidence that the channel assembles with twofold symmetry.

PMID- 20698643
TI  - Alpha-selective Ni-catalyzed hydroalumination of aryl- and alkyl-substituted
      terminal alkynes: practical syntheses of internal vinyl aluminums, halides, or
      boronates.
AB  - A method for Ni-catalyzed hydroalumination of terminal alkynes, leading to the
      formation of alpha-vinylaluminum isomers efficiently (>98% conv in 2-12 h) and
      with high selectivity (95% to >98% alpha), is described. Catalytic alpha
      selective hydroalumination reactions proceed in the presence of a reagent
      (diisobutylaluminum hydride; dibal-H) and 3.0 mol % metal complex (Ni(dppp)Cl(2))
      that are commercially available and inexpensive. Under the same conditions, but
      with Ni(PPh(3))(2)Cl(2), hydroalumination becomes highly beta-selective, and,
      unlike uncatalyzed transformations with dibal-H, generates little or no
      alkynylaluminum byproducts. All hydrometalation reactions are reliable,
      operationally simple, and practical and afford an assortment of vinylaluminums
      that are otherwise not easily accessible. The derived alpha-vinyl halides and
      boronates can be synthesized through direct treatment with the appropriate
      electrophiles [e.g., Br(2) and methoxy(pinacolato)boron, respectively]. Ni
      catalyzed hydroaluminations can be performed with as little as 0.1 mol % catalyst
      and on gram scale with equally high efficiency and selectivity.

PMID- 20698644
TI  - Mechanochromic and thermochromic luminescence of a copper iodide cluster.
AB  - The mechanochromic and thermochromic luminescence properties of a molecular
      copper(I) iodide cluster formulated [Cu(4)I(4)(PPh(2)(CH(2)CH=CH(2)))(4)] are
      reported. Upon mechanical grinding in a mortar, its solid-state emission
      properties are drastically modified as well as its thermochromic behavior. This
      reversible phenomenon has been attributed to distortions in the crystal packing
      leading to modifications of the intermolecular interactions and thus of the
      [Cu(4)I(4)] cluster core geometry. Notably, modification of the Cu-Cu
      interactions seems to be involved in this phenomenon directly affecting the
      emissive properties of the cluster.

PMID- 20698645
TI  - Size selection and concentration of silver nanoparticles by tangential flow
      ultrafiltration for SERS-based biosensors.
AB  - A proposed tangential flow ultrafiltration method was compared to the widely used
      ultracentrifugation method for efficiency and efficacy in concentrating, size
      selecting, and minimizing the aggregation state of a silver nanoparticle (AgNP)
      colloid while probing the AgNPs' SERS-based sensing capabilities. The
      ultrafiltration method proved to be more efficient and more effective and was
      found to tremendously boost the SERS-based sensing capabilities of these AgNPs
      through the increased number of homogeneous SERS hot spots available for a
      biotarget molecule within a minimal focal volume. Future research studies and
      applications addressing the physiochemical properties or biological impact of
      AgNPs would greatly benefit from ultrafiltration for its ability to generate
      monodisperse colloidal nanoparticles, to eliminate excess toxic chemicals from
      nanoparticle synthesis, and to obtain minimum levels of aggregation during
      nanoparticle concentration.

PMID- 20698646
TI  - Mysteries of TOPSe revealed: insights into quantum dot nucleation.
AB  - We have investigated the reaction mechanism responsible for QD nucleation using
      optical absorption and nuclear magnetic resonance spectroscopies. For typical II
      VI and IV-VI quantum dot (QD) syntheses, pure tertiary phosphine selenide sources
      (e.g., trioctylphosphine selenide (TOPSe)) were surprisingly found to be
      unreactive with metal carboxylates and incapable of yielding QDs. Rather, small
      quantities of secondary phosphines, which are impurities in tertiary phosphines,
      are entirely responsible for the nucleation of QDs; their low concentrations
      account for poor synthetic conversion yields. QD yields increase to nearly
      quantitative levels when replacing TOPSe with a stoiciometric amount of a
      secondary phosphine chalcogenide such as diphenylphosphine selenide. Based on our
      observations, we have proposed potential monomer identities, reaction pathways,
      and transition states and believe this mechanism to be universal to all II-VI and
      IV-VI QDs synthesized using phosphine based methods.

PMID- 20698647
TI  - Graphene-based SELDI probe with ultrahigh extraction and sensitivity for DNA
      oligomer.
AB  - We demonstrate that graphene can be used as an ultrahigh efficiency
      preconcentration and detection platform for ssDNA. DNA-adsorbed graphene can be
      used directly for Surface Enhanced Laser Desorption Ionization-Time of Flight
      Mass Spectrometry (SELDI-TOF-MS). The rapid enrichment of biomolecules and
      direct, label-free detection are potentially useful for analysis in proteomics
      and genomics.

PMID- 20698648
TI  - Main-group and transition-element IRMOF homologues.
AB  - A simple two-component procedure was developed to synthesize not only classical
      zinc-based IRMOFs represented by MOF-5 but also the cobalt and beryllium
      homologues of this most prominent MOF. The procedure is the first manifestation
      of mirroring the IRMOF series with other metal centers taken from main-group as
      well as transition-metal elements. Because of the existence of many suitable
      precursors, the procedure promises the generation of a large number of IRMOF
      homologues. Since the IRMOF series together with the MIL series is the MOF group
      with the largest number of representatives, the possibility of choosing the metal
      centers of the secondary building units from an extended set will tremendously
      expand the number of obtainable structures in a predictive, crystal-engineering
      type way. Use of metal centers other than zinc will allow the addition of new
      features to the existing IRMOF structures, such as magnetic properties in the
      example of cobalt.

PMID- 20698649
TI  - A potential site for trapping photogenerated holes on rutile TiO(2) surface as
      revealed by EPR spectroscopy: an avenue for enhancing photocatalytic activity.
AB  - Rutile TiO(2) nanoparticles with new sites for effectively trapping
      photogenerated holes have been prepared by reacting the TiO(2) nanoparticles
      prepared in hydrogen atmosphere with molecular oxygen at elevated temperatures.
      The observed g values and the occurrence of (47)Ti and (49)Ti octet hyperfine
      pattern allowed us to assign this EPR active center to surface oxygen centered
      anion radical with two coordinating titaniums. The effective trapping of
      photogenerated holes by these new sites inhibits the electron-hole recombination
      and results in an enhanced photocatalytic activity under visible light by a
      factor of 2.5 compared with samples prepared parallel in air. Oxidation of
      reduced TiO(2) apparently is a simple low-cost and promising route for improving
      the photoactivity of TiO(2).

PMID- 20698650
TI  - BaGe(5): a new type of intermetallic clathrate.
AB  - BaGe(5) constitutes a new type of intermetallic clathrate obtained by
      decomposition of clathrate-I Ba(8)Ge(43)(3) at low temperatures. The crystal
      structure consists of characteristic layers interconnected by covalent bonds.
      BaGe(5) is a semiconducting Zintl phase.

PMID- 20698651
TI  - Electrochemical synthesis and electrocatalytic properties of Au@Pt dendrimer
      encapsulated nanoparticles.
AB  - Dendrimer-encapsulated Au nanoparticles comprised of an average of 147 atoms were
      synthesized and immobilized on a glassy carbon electrode. A one-atom-thick shell
      of Cu was added to the Au core by electrochemical underpotential deposition, and
      then this shell was replaced with Pt by galvanic exchange. The results indicate
      that this synthetic approach leads to well-defined core/shell nanoparticles <2 nm
      in diameter. The rates of oxygen reduction at the Au@Pt electrocatalysts were
      compared to Pt-only and Au-only, 147-atom dendrimer-encapsulated nanoparticles.

PMID- 20698652
TI  - Fast water oxidation using iron.
AB  - Photolysis of water, a long-studied strategy for storing solar energy, involves
      two half-reactions: the reduction of protons to dihydrogen and the oxidation of
      water to dioxygen. Proton reduction is well-understood, with catalysts achieving
      quantum yields of 34% when driven by visible light. Water oxidation, on the other
      hand, is much less advanced, typically involving expensive metal centers and
      rarely working in conjunction with a photochemically powered system. Before
      further progress can be made in the field of water splitting, significant
      developments in the catalysis of oxygen evolution are needed. Herein we present
      an iron-centered tetraamido macrocyclic ligand (Fe-TAML) that efficiently
      catalyzes the oxidative conversion of water to dioxygen. When the catalyst is
      combined in unbuffered solution with ceric ammonium nitrate, its turnover
      frequency exceeds 1.3 s(-1). Real-time UV-vis and oxygen monitoring of the active
      complex give insights into the reaction and decay kinetics.

PMID- 20698653
TI  - 13CHD2 methyl group probes of millisecond time scale exchange in proteins by 1H
      relaxation dispersion: an application to proteasome gating residue dynamics.
AB  - A pulse scheme is presented for quantifying millisecond time scale chemical
      exchange processes in proteins by measuring (1)H CPMG relaxation dispersion
      profiles of (13)CHD(2) methyl groups. The use of (13)CHD(2) isotopomers for (1)H
      methyl dispersion experiments eliminates problems with interconversion between
      differentially relaxing proton transitions that complicate the extraction of
      accurate exchange parameters when (13)CH(3) probes are used. Good agreement is
      demonstrated between extracted chemical shift differences from fits of dispersion
      profiles and the corresponding differences measured independently on a model
      exchanging system, validating the experiment. The methodology is applied to the
      gating residues of the T. acidiphilium proteasome that are shown to undergo
      extensive motion on the millisecond time scale.

PMID- 20698654
TI  - Energetics of intercavity diffusion in a simple model of a low-density p-tert
      butylcalix[4]arene crystal.
AB  - Potentials of mean force calculated for the diffusion of small guest molecules
      (CO(2) and CH(4)) between adjacent host cavities in the beta(0) p-tert
      butylcalix[4]arene polymorph reveal sufficiently high barriers to diffusion to
      justify characterizing the lattice voids in this crystal as independent host
      cavities rather than as extended volumes. In addition, the calculated barrier
      heights are consistent with a "relay" model for gas diffusion in this ostensibly
      nonporous organic solid involving the lateral sliding of the host bilayers.

PMID- 20698655
TI  - Access to B=S and B=Se double bonds via sulfur and selenium insertion into a B-H
      bond and hydrogen migration.
AB  - Stable compounds with a boron-chalcogen (S or Se) valence double bond have been
      prepared via sequences involving insertion of the chalcogen into a B-H bond and
      subsequent hydrogen migration. X-ray diffraction studies and density functional
      theory calculations on the resulting compounds provide convincing evidence for
      the boron-chalcogen multiple bonding.

PMID- 20698656
TI  - Synthesis and photodynamics of 9-mesitylacridinium ion-modified gold
      nanoclusters.
AB  - Photoexcitation of gold nanoclusters covalently functionalized with 9-mesityl-10
      methylacridinium ion (Mes-Acr(+)) resulted in the formation of the electron
      transfer state (Mes(*+)-Acr(*)), which forms a pi-dimer radical cation with the
      neighboring Mes-Acr(+) via an intramolecular pi-pi interaction.

PMID- 20698657
TI  - Cyclobutenone as a highly reactive dienophile: expanding upon Diels-Alder
      paradigms.
AB  - Cyclobutenone was employed as a dienophile in Diels-Alder cycloadditions, provide
      diverse and complex cycloadducts in good yields. Experimental outcomes indicated
      cyclobutenone to be more reactive than either cyclopentenone or cyclohexenone. In
      addition, cycloadducts bearing a strained cyclobutanone moiety were able to
      undergo regioselective ring expansions to produce corresponding cyclopentanones,
      lactones, and lactams, which are otherwise difficultly obtained by direct Diels
      Alder reactions.

PMID- 20698658
TI  - A combined experimental-computational investigation of carbon dioxide capture in
      a series of isoreticular zeolitic imidazolate frameworks.
AB  - A series of five zeolitic imidazolate frameworks (ZIFs) have been synthesized
      using zinc(II) acetate and five different 4,5-functionalized imidazole units,
      namely ZIF-25, -71, -93, -96, and -97. These 3-D porous frameworks have the same
      underlying topology (RHO) with Brunauer-Emmet-Teller surface areas ranging from
      564 to 1110 m(2)/g. The only variation in structure arises from the functional
      groups that are directed into the pores of these materials, which include -CH(3),
      -OH, -Cl, -CN, -CHO, and -NH(2); therefore these 3-D frameworks are ideal for the
      study of the effect of functionality on CO(2) uptake. Experimental results show
      CO(2) uptake at approximately 800 Torr and 298 K ranging from 0.65 mmol g(-1) in
      ZIF-71 to 2.18 mmol g(-1) in ZIF-96. Molecular modeling calculations reproduce
      the pronounced dependence of the equilibrium adsorption on functionalization and
      suggest that polarizability and symmetry of the functionalization on the
      imidazolate are key factors leading to high CO(2) uptake.

PMID- 20698659
TI  - Cu(I)-catalyzed regioselective diamination of conjugated dienes via dual
      mechanistic pathways.
AB  - This paper describes the Cu(I)-catalyzed regioselective diamination of conjugated
      dienes using di-tert-butyldiaziridinone as nitrogen source. The internal
      diamination and terminal diamination likely proceed via two mechanistic pathways.
      Various dienes can be efficiently diaminated at the internal double bonds with
      high regio- and diasteroselectivity in good yield using inexpensive CuBr as
      catalyst.

PMID- 20698660
TI  - Synthesis and electronic properties of extended, fused-ring aromatic systems
      containing multiple pentalene units.
AB  - A series of elongated dibenzopentalenes were synthesized via a Pd-catalyzed
      cyclization followed by an Fe-mediated cyclodehydrogenation. Structural
      geometries varying from linear to extremely bent are shown to drastically
      influence solubility properties as well as reduction potentials. Comparisons are
      made to monopentalenes and related diindenoindacenes. UV-vis absorption spectra
      and cyclic voltammetry measurements indicate a strong modulation of the
      electronic structure of these compounds mediated by the strength of interactions
      between pentalene centers.

PMID- 20698661
TI  - Self-confirming "AND" logic nanoparticles for fault-free MRI.
AB  - Achieving high accuracy in the imaging of biological targets is a challenging
      issue. For MRI, to enhance imaging accuracy, two different imaging modes with
      specific contrast agents are used; one is a T1 type for a "positive" MRI signal
      and the other is a T2 type for a "negative" signal. Conventional contrast agents
      respond only in a single imaging mode and frequently encounter ambiguities in the
      MR images. Here, we propose a "magnetically decoupled" core-shell design concept
      to develop a dual mode nanoparticle contrast agent (DMCA). This DMCA not only
      possesses superior MR contrast effects but also has the unique capability of
      displaying "AND" logic signals in both the T1 and T2 modes. The latter enables
      self-confirmation of images and leads to greater diagnostic accuracy. A variety
      of novel DMCAs are possible, and the use of DMCAs can potentially bring the
      accuracy of MR imaging of diseases to a higher level.

PMID- 20698662
TI  - Photoswitchable catalysis mediated by dynamic aggregation of nanoparticles.
AB  - Catalytic activity of gold nanoparticles in a hydrosilylation reaction is
      controlled by irradiation with UV or visible light. When exposed to UV, the
      particles aggregate and the catalysis is effectively switched "off". When the
      particles are exposed to visible light, the particles redisperse and catalysis
      can proceed.

PMID- 20698663
TI  - Synthesis and characterization of teranthene: a singlet biradical polycyclic
      aromatic hydrocarbon having Kekule structures.
AB  - A teranthene derivative has been successfully isolated in a crystalline form for
      the first time. Geometrical considerations and physical property investigations
      indicate that the molecule possesses prominent biradical character in the ground
      state.

PMID- 20698664
TI  - High density orthogonal surface immobilization via photoactivated copper-free
      click chemistry.
AB  - Surfaces containing reactive ester polymer brushes were functionalized with
      cyclopropenone-masked dibenzocyclooctynes for the light activated immobilization
      of azides using catalyst-free click chemistry. The photodecarbonylation reaction
      in the amorphous brush layer is first order for the first 45 s with a rate
      constant of 0.022 s(-1). The catalyst-free cycloaddition of surface bound
      dibeznocyclooctynes proceeds rapidly in the presence of azides under ambient
      conditions. Photolithography using a shadow mask was used to demonstrate
      patterning with multiple azide containing molecules. This surface immobilization
      strategy provides a general and facile platform for the generation of
      multicomponent surfaces with spatially resolved chemical functionality.

PMID- 20698665
TI  - Asymmetric Suzuki cross-couplings of activated secondary alkyl electrophiles:
      arylations of racemic alpha-chloroamides.
AB  - A nickel-catalyzed stereoconvergent method for the enantioselective Suzuki
      arylation of racemic alpha-chloroamides has been developed. This process provides
      a unique example of an asymmetric arylation of an alpha-haloamide, an
      enantioselective arylation of an alpha-chlorocarbonyl compound, and an asymmetric
      Suzuki reaction with an activated alkyl electrophile or an arylboron reagent. The
      method is also applicable to the corresponding enantioselective cross-coupling of
      alpha-bromoamides. The coupling products can be transformed without racemization
      into enantioenriched alpha-arylcarboxylic acids and primary alcohols. A modest
      kinetic resolution of the alpha-chloroamide was observed; a mechanistic study
      indicated that the selectivity may reflect discrimination by the chiral catalyst
      of the two enantiomeric alpha-chloroamides in an irreversible oxidative-addition
      process.

PMID- 20698666
TI  - A photochemical metallocene route to anionic enediynes: synthesis, solid-state
      structures, and ab initio computations on cyclopentadienidoenediynes.
AB  - The first demonstration of photochemical enediyne liberation from a metal complex
      has led to a new class of enediynes, the cyclopentadienidoenediynes, which are
      demonstrated to exist as air-stable solids with low ionization potentials and
      large dipole moments. NMR and IR spectroscopy, X-ray crystallography, and ab
      initio computations enable a comparison with the ubiquitous benzoenediynes.

PMID- 20698667
TI  - Chemoselective and regiospecific Suzuki coupling on a multisubstituted sp(3)
      carbon in 1,1-diborylalkanes at room temperature.
AB  - The palladium-catalyzed Suzuki-Miyaura cross-coupling on a multisubstituted sp(3)
      carbon in 1,1-diborylalkanes was achieved at room temperature. The generation of
      a monoborate intermediate by virtue of the adjacent B atom could result in the
      chemoselective coupling reaction under ambient conditions.

PMID- 20698668
TI  - Pulling genetic RNA out of tobacco mosaic virus using single-molecule force
      spectroscopy.
AB  - RNA-coat protein interactions in intact tobacco mosaic virus have been
      investigated for the first time directly on the single-molecule level by pulling
      the genetic RNA step by step out of the helical groove formed by its protein
      coat. The effects of pulling speed and pH on RNA-protein interactions are
      presented. In addition, the rebinding behavior of the detached RNA with the
      protein coat is discussed. Our results demonstrate the possibility of studying
      nucleic acid-protein interactions in more complicated systems using AFM-based
      single-molecule force spectroscopy.

PMID- 20698669
TI  - Formal [2 + 2 + 2] cycloaddition strategy based on an intramolecular propargylic
      ene reaction/Diels-Alder cycloaddition cascade.
AB  - A formal, metal-free, [2 + 2 + 2] cycloaddition strategy is described based on a
      cascade of two pericyclic processes. The first step involves an intramolecular
      propargylic ene reaction of a 1,6-diyne to generate a vinylallene, which then
      reacts in an inter- or intramolecular Diels-Alder reaction with an alkenyl or
      alkynyl dienophile. Reactions involving unsymmetrical alkenyl and alkynyl
      dienophiles proceed with good to excellent regioselectivity, and the
      diastereoselectivity in the Diels-Alder step is also high, with endo cycloadducts
      produced as the exclusive products of the reaction. In the case of alkynyl
      dienophiles, [4 + 2] cycloaddition initially generates an isotoluene-type
      intermediate that isomerizes to the isolated aromatic product upon exposure to a
      catalytic amount of DBU at room temperature. The mechanism of several earlier
      fully intramolecular related transformations have been shown to involve an
      analogous process rather than the diradical-mediated pathways proposed
      previously.

PMID- 20698670
TI  - Protecting-group-free and catalysis-based total synthesis of the
      ecklonialactones.
AB  - A concise and protecting-group-free total synthesis of optically pure
      ecklonialactones A (1) and B (2) is described. The successful route to these
      oxylipins isolated from various brown algae involves five transition-metal
      catalyzed transformations in the longest linear sequence of 13 steps. The first
      chiral center was set by a rhodium-catalyzed 1,4-addition of an alkenyl boronate
      to the commercial butenolide 11, which was controlled by Carreira's carvone
      derived diene ligand 21. Other key steps involve a ring-closing olefin metathesis
      effected by the ruthenium indenylidene complex 22 for the formation of the five
      membered carbocycle, a vanadium-catalyzed, hydroxy-directed epoxidation, and a
      ring-closing alkyne metathesis (RCAM) to forge the macrocyclic ring. Because of
      the unusually high propensity of the oxirane of the ecklonialactones for ring
      opening, this transformation was best achieved with [(Ph(3)SiO)(3)Mo[triple
      bond]CPh].OEt(2) (34) as the catalyst, which is a representative of a new
      generation of highly tolerant yet remarkably efficient molybdenum alkylidyne
      complexes. The ancillary triphenylsilanolate ligands in 34 temper the Lewis
      acidity of the molybdenum center and are not able to nucleophilically open the
      fragile epoxide ring. The final reduction of the cycloalkyne formed in the RCAM
      step to the required (Z)-alkene was accomplished either by Lindlar reduction or
      with the aid of nickel boride.

PMID- 20698671
TI  - Practical new silyloxy-based alkyne metathesis catalysts with optimized activity
      and selectivity profiles.
AB  - Triphenylsilanolate ligands were found to impart excellent reactivity and
      outstanding functional group tolerance on molybdenum alkylidyne complexes, which
      catalyze alkyne metathesis reactions of all sorts. The active species either can
      be obtained in high yield by adaptation of the established synthesis routes
      leading to Schrock alkylidynes or can be generated in situ from the molybdenum
      nitride complex 11, which itself is readily accessible in large quantity from
      inexpensive sodium molybdate. Complexation of the active silanolate complexes 12
      and 24 with 1,10-phenanthroline affords complexes 15 and 25, respectively, which
      are stable in air for extended periods of time. Although these phenathroline
      adducts are per se unreactive vis-a-vis alkynes, catalytic activity is
      conveniently restored upon exposure to MnCl(2). Therefore, the practitioner has
      the choice of different alkyne metathesis (pre)catalysts, which are easy to
      handle yet broadly applicable and exceedingly tolerant. A host of representative
      inter- as well as intramolecular alkyne metathesis reactions, including
      applications to a considerable number of bioactive and, in part, labile natural
      products, shows the remarkable scope of these new tools. Moreover, it was found
      that the addition of molecular sieves (5 A >or= 4 A >> 3 A) to the reaction
      mixture significantly improves the chemical yields while simultaneously
      increasing the reaction rates. This benefit is ascribed to effective binding of 2
      butyne, which is released as the common byproduct in reactions of alkynes bearing
      a methyl end-cap. Thus, alkyne metatheses can now be performed at ambient
      temperature with neither the need to apply vacuum to drive the conversion nor
      recourse to tailor-made substrates. The structures of representative examples of
      this new generation of alkyne metathesis catalysts in the solid state were
      determined by X-ray analysis.

PMID- 20698673
TI  - Free-energy surfaces for liquid-phase reactions and their use to study the border
      between concerted and nonconcerted alpha,beta-elimination reactions of esters and
      thioesters.
AB  - Distinguishing between the concerted second-order mechanism for beta-eliminations
      and nonconcerted mechanisms with discrete carbanion intermediates is very
      difficult experimentally, but the ability of quantum chemistry to find stationary
      points of the free-energy surface in liquid-phase solutions, even for complex
      reagents, provides a new tool for elucidating such mechanisms. Here we use liquid
      phase density functional theory calculations to find transition states and
      intermediates on the free-energy surfaces of four base-initiated alpha,beta
      eliminations of acetoxy and mesyloxy esters and their analogous thioesters. The
      geometries, free energies, and charge distributions of these structures support a
      stepwise irreversible first-order elimination from a conjugate base (E1cB(I))
      mechanism with acetoxy ester 3, acetoxy thioester 4, and mesyloxy thioester 6.
      However, mesyloxy ester 5, which has an excellent nucleofuge and a less-acidic
      proton, follows a concerted but asynchronous E2 mechanism with an E1cB-like
      transition state. The anti transition state is more favorable than the syn one,
      even for the poorer nucleofuge and more-acidic thioesters. The article includes a
      general scheme for describing liquid-phase reactions in terms of free-energy
      surfaces.

PMID- 20698672
TI  - Constraining binding hot spots: NMR and molecular dynamics simulations provide a
      structural explanation for enthalpy-entropy compensation in SH2-ligand binding.
AB  - NMR spectroscopy and molecular dynamics (MD) simulations were used to probe the
      structure and dynamics of complexes of three phosphotyrosine-derived peptides
      with the Src SH2 domain in an effort to uncover a structural explanation for
      enthalpy-entropy compensation observed in the binding thermodynamics. The series
      of phosphotyrosine peptide derivatives comprises the natural pYEEI Src SH2
      ligand, a constrained mimic, in which the phosphotyrosine (pY) residue is
      preorganized in the bound conformation for the purpose of gaining an entropic
      advantage to binding, and a flexible analogue of the constrained mimic. The
      expected gain in binding entropy of the constrained mimic was realized; however,
      a balancing loss in binding enthalpy was also observed that could not be
      rationalized from the crystallographic structures. We examined protein dynamics
      to evaluate whether the observed enthalpic penalty might be the result of effects
      arising from altered motions in the complex. (15)N-relaxation studies and
      positional fluctuations from molecular dynamics indicate that the main-chain
      dynamics of the protein show little variation among the three complexes. Root
      mean squared (rms) coordinate deviations vary by less than 1.5 A for all non
      hydrogen atoms for the crystal structures and in the ensemble average structures
      calculated from the simulations. In contrast to this striking similarity in the
      structures and dynamics, there are a number of large chemical shift differences
      from residues across the binding interface, but particularly from key Src SH2
      residues that interact with pY, the "hot spot" residue, which contributes about
      one-half of the binding free energy. Rank-order correlations between chemical
      shifts and ligand binding enthalpy for several pY-binding residues, coupled with
      available mutagenesis and calorimetric data, suggest that subtle structural
      perturbations (<1 A) from the conformational constraint of the pY residue
      sufficiently alter the geometry of enthalpically critical interactions in the
      binding pocket to cause the loss of binding enthalpy, leading to the observed
      enthalpy-entropy compensation. We find no evidence to support the premise that
      enthalpy-entropy compensation is an inherent property and conclude that
      preorganization of Src SH2 ligand residues involved in binding hot spots may
      eventuate in suboptimal interactions with the domain. We propose that introducing
      constraints elsewhere in the ligand could minimize enthalpy-entropy compensation
      effects. The results illustrate the utility of the NMR chemical shift to
      highlight small, but energetically significant, perturbations in structure that
      might otherwise go unnoticed in an apparently rigid protein.

PMID- 20698674
TI  - Control of the orientational order and nonlinear optical response of the "push
      pull" chromophore RuPZn via specific incorporation into densely packed monolayer
      ensembles of an amphiphilic four-helix bundle peptide: characterization of the
      peptide-chromophore complexes.
AB  - "Push-pull" chromophores based on extended pi-electron systems have been designed
      to exhibit exceptionally large molecular hyperpolarizabilities. We have
      engineered an amphiphilic four-helix bundle peptide to vectorially incorporate
      such hyperpolarizable chromophores having a metalloporphyrin moiety, with high
      specificity into the interior core of the bundle. The amphiphilic exterior of the
      bundle facilitates the formation of densely packed monolayer ensembles of the
      vectorially oriented peptide-chromophore complexes at the liquid-gas interface.
      Chemical specificity designed into the ends of the bundle facilitates the
      subsequent covalent attachment of these monolayer ensembles onto the surface of
      an inorganic substrate. In this article, we describe the structural
      characterization of these monolayer ensembles at each stage of their fabrication
      for one such peptide-chromophore complex designated as AP0-RuPZn. In the
      accompanying article, we describe the characterization of their macroscopic
      nonlinear optical properties.

PMID- 20698675
TI  - Visualizing proton antenna in a high-resolution green fluorescent protein
      structure.
AB  - "Proton-collecting antenna" are conjectured to consist of several carboxylates
      within hydrogen-bond (HB) networks on the surface of proteins, which funnel
      protons to the orifice of an internal proton wire leading to the protein's active
      site. Yet such constructions were never directly visualized. Here we report an X
      ray structure of green fluorescent protein (GFP) of the highest resolution to
      date (0.9 A). It allows the identification of some pivotal hydrogen atoms
      pertinent to uncertainties concerning the protonation state of the chromophore.
      Applying a computer algorithm for mapping proton wires in proteins reveals the
      previously observed "active site wire" connecting Glu222 with the surface
      carboxylate Glu5. In addition, it is now possible to identify what appears to be
      a proton-collecting apparatus of GFP. It consists of a negative surface patch
      containing carboxylates, threonines, and water molecules, connected by a HB
      network to Glu5. Furthermore, we detect exit points via Asn146 and His148 to a
      hydrophobic surface region. The more extensive HB network of the present
      structure, as compared with earlier GFP structures, is not accidental. A
      systematic investigation of over 100 mutants shows a clear correlation between
      the observed water content of GFP X-ray structures and their resolution. With
      increasing water content, the proton wires become progressively larger. These
      findings corroborate the scenario in which the photodissociated proton from wild
      type GFP can leak outside, whereafter another proton is recruited via the proton
      collecting apparatus reported herein.

PMID- 20698677
TI  - A new family of nonionic dendritic amphiphiles displaying unexpected packing
      parameters in micellar assemblies.
AB  - In this paper we report on the synthesis of a new family of nonionic dendritic
      amphiphiles that self-assemble into defined supramolecular aggregates. Our
      approach is based on a modular architecture consisting of different generations
      of hydrophilic polyglycerol dendrons [G1-G3] connected to hydrophobic C(11) or
      C(16) alkyl chains via mono- or biaromatic spacers, respectively. All amphiphiles
      complex hydrophobic compounds as demonstrated by solubilization of Nile Red or
      pyrene. The structure of the supramolecular assemblies as well as the aggregation
      numbers are strongly influenced by the type of the dendritic headgroup. While the
      [G1] amphiphiles form different structures such as ringlike and fiberlike
      micelles, the [G2] and [G3] derivatives aggregate toward spherical micelles of
      low polydispersity clearly proven by transmission electron microscopy (TEM)
      measurements. In the case of the biaromatic [G2] derivative, the structural
      persistence of the micelles allowed a three-dimensional structure determination
      from the TEM data and confirmed the aggregation number obtained by static light
      scattering (SLS) measurements. On the basis of these data, molecular packing
      geometries indicate a drastic mass deficit of alkyl chains in the hydrophobic
      core volume of spherical micelles. It is noteworthy that these highly defined
      micelles contain as little as 15 molecules and possess up to 74% empty space.
      This behavior is unexpected as it is very different from classical detergent
      micelles such as sodium dodecyl sulfate (SDS), where the hydrophobic core volume
      is completely filled by alkyl chains.

PMID- 20698678
TI  - Selective synthesis of subnanometer diameter semiconducting single-walled carbon
      nanotubes.
AB  - Subnanometer single-walled carbon nanotubes (sub-nm SWNTs) were synthesized at
      different temperatures (600, 700, and 800 degrees C) using CoMn bimetallic
      catalysts supported on MCM-41 silica templates. The state of the catalyst was
      investigated using X-ray absorption, and the (n,m) indices of the sub-nm SWNTs
      were determined from Raman spectroscopy and photoluminescence measurements. We
      find that the size of the metallic particles that seed the growth of sub-nm SWNTs
      (diameter approximately 0.5-1.0 nm) is highly sensitive to the reaction
      temperature. Low reaction temperature (600 degrees C) favors the growth of
      semiconducting tubes whose diameters range from 0.5 to 0.7 nm. These results were
      also confirmed by electrical transport measurements. Interestingly, dominant
      intermediate frequency modes on the same intensity scale as the Raman breathing
      modes were observed. An unusual "S-like" dispersion of the G-band was present in
      the Raman spectra of sub-nm SWNTs with diameters <0.7 nm.

PMID- 20698676
TI  - Fluorogenic dendrons with multiple donor chromophores as bright genetically
      targeted and activated probes.
AB  - We have developed a class of dendron-based fluorogenic dyes (termed dyedrons)
      comprised of multiple cyanine (Cy3) donors coupled to a single malachite green
      (MG) acceptor that fluoresce only when the MG is noncovalently but specifically
      bound to a cognate single chain antibody (scFv). These cell-impermeant dyedrons
      exploit efficient intramolecular energy transfer from Cy3 donors to
      stoichiometrically amplify the fluorescence of MG chromophores that are activated
      by binding to the scFv. These chromophore enhancements, coupled with our
      optimized scFv, can significantly increase fluorescence emission generated by the
      dyedron/scFv complex to brightness levels several-fold greater than that for
      single fluorescent proteins and targeted small molecule fluorophores. Efficient
      intramolecular quenching of free dyedrons enables sensitive homogeneous (no wash)
      detection under typical tissue culture conditions, with undetectable nonspecific
      activation.

PMID- 20698679
TI  - Layer-by-layer self-assembled osmium polymer-mediated laccase oxygen cathodes for
      biofuel cells: the role of hydrogen peroxide.
AB  - High potential purified Trametes trogii laccase has been studied as a biocatalyst
      for oxygen cathodes composed of layer-by-layer self-assembled thin films by
      sequential immersion of mercaptopropane sulfonate-modified Au electrode surfaces
      in solutions containing laccase and osmium-complex bound to poly(allylamine),
      (PAH-Os). The polycation backbone carries the Os redox relay, and the polyanion
      is the enzyme adsorbed from a solution of a suitable pH so that the protein
      carries a net negative charge. Enzyme thin films were characterized by quartz
      crystal microbalance, ellipsometry, cyclic voltammetry, and oxygen reduction
      electrocatalysis under variable oxygen partial pressures with a rotating disk
      electrode. New kinetic evidence relevant to biofuel cells is presented on the
      detection of traces of H(2)O(2), intermediate in the O(2) reduction, with
      scanning electrochemical microscopy (SECM). Furthermore the inhibitory effect of
      peroxide on the biocatalytic current resulted in abnormal current dependence on
      the O(2) partial pressure and peak shape with hysteresis in the polarization
      curves under stagnant conditions, which is offset upon stirring with the RDE. The
      new kinetic evidence reported in the present work is very relevant for the
      operation of biofuel cells under stagnant conditions of O(2) mass transport.

PMID- 20698680
TI  - Synthetic analogs tailor native AI-2 signaling across bacterial species.
AB  - The widespread use of antibiotics and the emergence of resistant strains call for
      new approaches to treat bacterial infection. Bacterial cell-cell communication or
      "quorum sensing" (QS) is mediated by "signatures" of small molecules that
      represent targets for "quenching" communication and avoiding virulent phenotypes.
      Only a handful of small molecules that antagonize the action of the "universal"
      autoinducer, AI-2, have been reported. The biological basis of antagonism, as
      well as the targets for these select few AI-2 antagonists, have not been clearly
      defined. We have developed C-1 alkyl analogs of AI-2 that quench the QS response
      in multiple bacterial species simultaneously. We also demonstrate the biological
      basis for this action. Like AI-2, the analogs are activated by the bacterial
      kinase, LsrK, and modulate AI-2 specific gene transcription through the
      transcriptional regulator, LsrR. Interestingly, addition of a single carbon to
      the C1-alkyl chain of the analog plays a crucial role in determining the effect
      of the analog on the QS response. While an ethyl modified analog is an agonist,
      propyl becomes an antagonist of the QS circuit. In a trispecies synthetic
      ecosystem comprised of E. coli, S. typhimurium, and V. harveyi we discovered both
      cross-species and species-specific anti-AI-2 QS activities. Our results suggest
      entirely new modalities for interrupting or tailoring the network of
      communication among bacteria.

PMID- 20698681
TI  - Synthesis, structure, and density functional theory analysis of a scandium
      dinitrogen complex, [(C(5)Me(4)H)(2)Sc](2)(mu-eta(2):eta(2)-N(2)).
AB  - Investigation of the bis(tetramethylcyclopentadienyl) metallocene chemistry of
      scandium has revealed that the method involving reduction of trivalent salts with
      alkali metals used with lanthanides can also be applied to scandium to make a
      dinitrogen complex of the first member of the transition metal series. ScCl(3)
      reacts with 2 equiv of KC(5)Me(4)H to form (C(5)Me(4)H)(2)ScCl(THF), 1, which
      reacts with allylmagnesium chloride to make (C(5)Me(4)H)(2)Sc(eta(3)-C(3)H(5)),
      2. Complex 2 reacts with [HNEt(3)][BPh(4)] to yield [(C(5)Me(4)H)(2)Sc][(mu
      Ph)BPh(3)], 3, which has just one primary Sc-C(phenyl) contact connecting the
      tetraphenylborate anion and the metallocene cation. Treatment of 3 with KC(8) in
      THF under N(2) generates [(C(5)Me(4)H)(2)Sc](2)(mu-eta(2):eta(2)-N(2)), which has
      a coplanar arrangement of scandium and nitrogen atoms within a square planar
      array of tetramethylcyclopentadienyl rings. Density functional calculations
      explain the bonding that results in the 1.239(3) A N-N bond distance in the
      (N=N)(2-) moiety.

PMID- 20698682
TI  - Folding of a helix at room temperature is critically aided by electrostatic
      polarization of intraprotein hydrogen bonds.
AB  - We report direct folding of a 17-residue helix protein (pdb:2I9M) by standard
      molecular dynamics simulation (single trajectory) at room temperature with
      implicit solvent. Starting from a fully extended structure, 2I9M successfully
      folds into the native conformation within 16 ns using adaptive hydrogen bond
      specific charges to take into account the electrostatic polarization effect.
      Cluster analysis shows that conformations in the native state cluster have the
      highest population (78.4%) among all sampled conformations. Folding snapshots and
      the secondary structure analysis demonstrate that the folding of 2I9M begins at
      terminals and progresses toward the center. A plot of the free energy landscape
      indicates that there is no significant free energy barrier during folding, which
      explains the observed fast folding speed. For comparison, exactly the same
      molecular dynamics simulation but carried out under existing AMBER charges failed
      to fold 2I9M into native-like structures. The current study demonstrates that
      electrostatic polarization of intraprotein hydrogen bonding, which stabilizes the
      helix, is critical to the successful folding of 2I9m.

PMID- 20698683
TI  - Antisense-induced guanine quadruplexes inhibit reverse transcription by HIV-1
      reverse transcriptase.
AB  - Guanine quadruplex structures in DNA and RNA affect normal cellular processes
      such as replication, recombination, and translation. Thus, controlling guanine
      quadruplex structures could make it possible to manipulate the biological
      function of nucleic acids. Here, we report a novel antisense strategy using
      guanine-tethered antisense oligonucleotides (g-ASs) that introduces an RNA-DNA
      heteroquadruplex structure on RNA templates in a predictable and sequence
      specific manner, which in practice effectively inhibited reverse transcription on
      a variety of RNA sequences, including the HIV-1 RNA genome. Reverse transcriptase
      mediated enzymatic analysis, together with other biophysical analyses, elucidated
      a cooperative binding of duplex and quadruplex in g-AS-RNA complexes. The
      remarkable ability of g-ASs to inhibit reverse transcription could make possible
      the development of novel anti-retroviral gene therapies based on blocking the
      replication of RNA genomes to complementary DNA, which is a critical step for
      integration into the host's genome.

PMID- 20698684
TI  - Intramolecular [1 + 4 + 1] cycloaddition: establishment of the method.
AB  - Structurally complex and physiologically active natural products often include
      bicyclic and polycyclic ring systems having defined relative and absolute
      configuration. Approaches that allow the construction of more than one
      carbocyclic ring at a time have proven valuable, in particular those that allow
      at the same time the control of an array of new stereogenic centers. One of the
      most general and most widely used protocols has been the intramolecular Diels
      Alder [4 + 2] cycloaddition, in which a single stereogenic center between the
      diene and the dienophile can control the relative and absolute configuration of
      the product. We report a two-step [1 + 4 + 1] procedure for bicyclic and
      polycyclic construction, based on the cyclization of an omega-dienyl ketone. This
      is complementary to, and will likely be as useful as, the intramolecular Diels
      Alder cycloaddition.

PMID- 20698685
TI  - Navigating the downhill protein folding regime via structural homologues.
AB  - Proteins that fold over free-energy barriers <or= 3RT are classified as downhill
      folders. This regime is characterized by equilibrium unfolding that is
      proportionally broader and more complex the lower the folding barrier. Downhill
      proteins are also expected to fold up in a few microseconds. However, the
      relationship between rate and equilibrium signatures is affected by other factors
      such as protein size and folding topology. Here we perform a direct comparison of
      the kinetics and equilibrium unfolding of two structural homologues: BBL and PDD.
      BBL folds-unfolds in just approximately 1 micros at 335 K and displays the
      equilibrium signatures expected for a protein at the bottom of the downhill
      folding regime. PDD, which has the same 3D structure and size, folds-unfolds
      approximately 8 times more slowly and, concomitantly, exhibits all the downhill
      equilibrium signatures to a lesser degree. Our results demonstrate that the
      equilibrium signatures of downhill folding are proportional to the changes in
      folding rate once structural and size-scaling effects are factored out. This
      conclusion has two important implications: (1) it confirms that the quantitative
      analysis of equilibrium experiments in ultrafast folding proteins does provide
      direct information about free-energy barriers, a result that is incompatible with
      the conventional view of protein folding as a highly activated process, and (2)
      it advocates for equilibrium-kinetic studies of homologous proteins as a powerful
      tool to navigate the downhill folding regime via comparative analysis. The latter
      should prove extremely useful for the investigation of sequence, functional, and
      evolutionary determinants of protein folding barriers.

PMID- 20698687
TI  - A tyrosyl-dimanganese coupled spin system is the native metalloradical cofactor
      of the R2F subunit of the ribonucleotide reductase of Corynebacterium
      ammoniagenes.
AB  - The X-ray crystallographic structure of the native R2F subunit of the
      ribonucleotide reductase (RNR) of Corynebacterium ammoniagenes ATCC 6872 is
      reported, with a resolution of 1.36 A. The metal site contains an oxo/hydroxo
      bridged manganese dimer, located near a tyrosine residue (Y115). The coordination
      of the manganese dimer and its distance to a nearby tyrosine residue resemble the
      di-iron metalloradical cofactor of class I RNR from Escherichia coli .
      Multifrequency EPR measurements of the highly active C. ammoniagenes R2F subunit
      show that the metal site contains a ferromagnetically exchange-coupled
      Mn(III)Mn(III) dimer weakly coupled to a tyrosyl radical. A mechanism for the
      metalloradical cofactor (Mn(III)Mn(III)Y(*)) generation is proposed. H(2)O(2)
      (HO(2)(-)) instead of O(2) is hypothesized as physiological oxidant for the Mn
      dimer which in turn oxidizes the tyrosine Y115. Changes in the ligand sphere of
      both manganese ions during metalloradical generation direct the complex formation
      of this cofactor, disfavoring alternate reaction pathways such as H(2)O(2)
      dismutation, as observed for manganese catalase, a structural analogue of the R2F
      metal site. The presented results demonstrate the importance of manganese for
      radical formation in this RNR and confirm the assignment of this enzyme to class
      Ib.

PMID- 20698686
TI  - NMR study of the exchange coupling in the trinuclear cluster of the multicopper
      oxidase Fet3p.
AB  - Fet3p from Saccharomyces cerevisiae is a multicopper oxidase (MCO) which oxidizes
      Fe(2+) to Fe(3+). The electronic structure of the different copper centers in
      this family of enzymes has been extensively studied and discussed for years with
      a particular focus on the exchange coupling regime in the trinuclear cluster
      (TNC). Using NMR spectroscopy we have quantified the exchange coupling constant
      in the type 3 center in a fully metalated oxidase; this value in Fet3p is
      significantly higher than that reported for proteins containing isolated type 3
      centers as tyrosinase. We also provide evidence of exchange coupling between the
      type 2 and the type 3 Cu(2+) ions, which supports the crystallographic evidence
      of dioxygen binding to the TNC. This work provides the foundation for the
      application of NMR to these complex systems.

PMID- 20698688
TI  - Hollow V(2)O(5) nanoparticles (fullerene-like analogues) prepared by laser
      ablation.
AB  - Nanoparticles of materials with layered structure are able to spontaneously form
      closed-cage nanostructures such as nested fullerene-like nanoparticles and
      nanotubes. This propensity has been demonstrated in a large number of compounds
      such as WS(2), NiCl(2), and others. Layered metal oxides possess a higher ionic
      character and consequently are stiffer and cannot be evenly folded. Vanadium
      pentoxide (V(2)O(5)), a layered metal oxide, has received much attention due to
      its attractive qualities in numerous applications such as catalysis and
      electronic and optical devices and as an electrode material for lithium
      rechargeable batteries. The synthesis by pulsed laser ablation (PLA) of V(2)O(5)
      hollow nanoparticles, which are closely (nearly) associated with inorganic
      "fullerene-like" (NIF-V(2)O(5)) nanoparticles, but not quite as perfect, is
      reported in the present work. The relation between the PLA conditions and the NIF
      V(2)O(5) morphology is elucidated. A new mechanism leading to hollow
      nanostructure via crystallization of lower density amorphous nanoparticles is
      proposed. Transmission electron microscopy (TEM) is used extensively in
      conjunction with structural modeling of the NIF-V(2)O(5) in order to study the
      complex 3-D structure of the NIF-V(2)O(5) nanoparticles. This structure was shown
      to be composed of facets with their low-energy surfaces pointing outward and
      seamed by defective domains. These understandings are used to formulate a
      formation mechanism and may improve the function of V(2)O(5) in its many uses
      through additional morphological control. Furthermore, this study outlines which
      properties are required from layered compounds to fold into perfectly closed-cage
      IF nanoparticles.

PMID- 20698689
TI  - Conformations, conformational preferences, and conformational exchange of N'
      substituted N-acylguanidines: intermolecular interactions hold the key.
AB  - Guanidine and acylguanidine groups are crucial structural features of numerous
      biologically active compounds. Depending on the biological target, acylguanidines
      may be considered as considerably less basic bioisosteres of guanidines with
      improved pharmacokinetics and pharmacodynamics, as recently reported for N'
      monoalkylated N-acylguanidines as ligands of G-protein-coupled receptors (GPCRs).
      The molecular basis for enhanced ligand-receptor interactions of acylguanidines
      is far from being understood. So far, only a few and contradictory results about
      their conformational preferences have been reported. In this study, the
      conformations, conformational preferences, and conformational exchange of four
      unprotonated and seven protonated monoalkylated acylguanidines with up to six
      anions and with bisphosphonate tweezers are investigated by NMR. Furthermore, the
      effects of the acceptor properties in acylguanidine salts, of microsolvation by
      dimethylsulfoxide, and of varying acyl and alkyl substituents are studied.
      Throughout the whole study, exclusively two out of eight possible acylguanidine
      conformations were detected, independent of the compound, the anion, or the
      solvent used. For the first time, it is shown that the strength and number of
      intermolecular interactions with anions, solvent molecules, or biomimetic
      receptors decide the conformational preferences and exchange rates. One recently
      presented and two new crystal structures resemble the conformational preferences
      observed in solution. Thus, consistent conformational trends are found throughout
      the structurally diverse compound pool, including two potent GPCR ligands,
      different anions, and receptors. The presented results may contribute to a better
      understanding of the mechanism of action at the molecular level and to the
      prediction and rational design of these biologically active compounds.

PMID- 20698690
TI  - Neutral transition metal hydrides as acids in hydrogen bonding and proton
      transfer: media polarity and specific solvation effects.
AB  - Structural, spectroscopic, and electronic features of weak hydrogen-bonded
      complexes of CpM(CO)(3)H (M = Mo (1a), W (1b)) hydrides with organic bases
      (phosphine oxides R(3)PO (R = n-C(8)H(17), NMe(2)), amines NMe(3), NEt(3), and
      pyridine) are determined experimentally (variable temperature IR) and
      computationally (DFT/M05). The intermediacy of these complexes in reversible
      proton transfer is shown, and the thermodynamic parameters (DeltaH degrees ,
      DeltaS degrees ) of each reaction step are determined in hexane. Assignment of
      the product ion pair structure is made with the help of the frequency
      calculations. The solvent effects were studied experimentally using IR
      spectroscopy in CH(2)Cl(2), THF, and CH(3)CN and computationally using conductor
      like polarizable continuum model (CPCM) calculations. This complementary approach
      reveals the particular importance of specific solvation for the hydrogen-bond
      formation step. The strength of the hydrogen bond between hydrides 1 and the
      model bases is similar to that of the M-H...X hydrogen bond between 1 and THF (X
      = O) or CH(3)CN (X = N) or between CH(2)Cl(2) and the same bases. The latter
      competitive weak interactions lower the activities of both the hydrides and the
      bases in the proton transfer reaction. In this way, these secondary effects shift
      the proton transfer equilibrium and lead to the counterintuitive hampering of
      proton transfer upon solvent change from hexane to moderately polar CH(2)Cl(2) or
      THF.

PMID- 20698691
TI  - Mechanism for recognition of polyubiquitin chains: balancing affinity through
      interplay between multivalent binding and dynamics.
AB  - RAP80 plays a key role in signal transduction in the DNA damage response by
      recruiting proteins to DNA damage foci by binding K63-polyubiquitin chains with
      two tandem ubiquitin-interacting motifs (tUIM). It is generally recognized that
      the typically weak interaction between ubiquitin (Ub) and various recognition
      motifs is intensified by themes such as tandem recognition motifs and Ub
      polymerization to achieve biological relevance. However, it remains an intricate
      problem to develop a detailed molecular mechanism to describe the process that
      leads to amplification of the Ub signal. A battery of solution-state NMR methods
      and molecular dynamics simulations were used to demonstrate that RAP80-tUIM
      employs mono- and multivalent interactions with polyUb chains to achieve enhanced
      affinity in comparison to monoUb interactions for signal amplification. The
      enhanced affinity is balanced by unfavorable entropic effects that include
      partial quenching of rapid reorientation between individual UIM domains and
      individual Ub domains in the bound state. For the RAP80-tUIM-polyUb interaction,
      increases in affinity with increasing chain length are a result of increased
      numbers of mono- and multivalent binding sites in the longer polyUb chains. The
      mono- and multivalent interactions are characterized by intrinsically weak
      binding and fast off-rates; these weak interactions with fast kinetics may be an
      important factor underlying the transient nature of protein-protein interactions
      that comprise DNA damage foci.

PMID- 20698692
TI  - Layer-by-layer assembly of three-dimensional colloidal supercrystals with tunable
      plasmonic properties.
AB  - We present a simple and efficient method for synthesizing large-area (>1 cm(2)),
      three-dimensional (3D) gold and silver nanoparticle supercrystal films. In this
      approach, Janus nanoparticle (top face solvent-phobic and bottom face solvent
      philic) films with an arbitrary number of close-packed nanoparticle monolayers
      can be formed using layer-by-layer (LbL) assembly from suspensions of thiolate
      passivated gold or silver colloids. Furthermore, we demonstrate that these films
      can act as true 3D plasmonic crystals with strong transverse (intralayer) and
      longitudinal (interlayer) near-field coupling. In contrast to conventional
      polyelectrolyte-mediated LbL assembly processes, this approach allows multiple
      longitudinal coupling modes with a conspicuous spectral dependence on the layer
      number. We have found a universal scaling relation between the spectral position
      of the reflectance dips related to the longitudinal modes and the layer number.
      This relation can be understood in terms of the presence of a plasmonic Fabry
      Perot nanocavity along the longitudinal direction that allows the formation of
      standing plasmon waves under plasmon resonance conditions. The realization of 3D
      plasmonic coupling enables broadband tuning of the collective plasmon response
      over a wide spectral range (visible and near-IR) and provides a pathway to
      designer plasmonic metamaterials.

PMID- 20698693
TI  - Design, synthesis, and imaging of an activatable photoacoustic probe.
AB  - Photoacoustic tomography is a rapidly growing imaging modality that can provide
      images of high spatial resolution and high contrast at depths up to 5 cm. We
      report here the design, synthesis, and evaluation of an activatable probe that
      shows great promise for enabling detection of the cleaved probe in the presence
      of high levels of nonactivated, uncleaved probe, a difficult task to attain in
      absorbance-based modality. Before the cleavage by its target, proteolytic enzyme
      MMP-2, the probe, an activatable cell-penetrating peptide,
      Ceeee[Ahx]PLGLAGrrrrrK, labeled with two chromophores, BHQ3 and Alexa750, shows
      photoacoustic signals of similar intensity at the two wavelengths corresponding
      to the absorption maxima of the chromophores, 675 and 750 nm. Subtraction of the
      images taken at these two wavelengths makes the probe effectively
      photoacoustically silent, as the signals at these two wavelengths essentially
      cancel out. After the cleavage, the dye associated with the cell-penetrating part
      of the probe, BHQ3, accumulates in the cells, while the other dye diffuses away,
      resulting in photoacoustic signal seen at only one of the wavelengths, 675 nm.
      Subtraction of the photoacoustic images at two wavelengths reveals the location
      of the cleaved (activated) probe. In the search for the chromophores that are
      best suited for photoacoustic imaging, we have investigated the photoacoustic
      signals of five chromophores absorbing in the near-infrared region. We have found
      that the photoacoustic signal did not correlate with the absorbance and
      fluorescence of the molecules, as the highest photoacoustic signal arose from the
      least absorbing quenchers, BHQ3 and QXL 680.

PMID- 20698694
TI  - Surface charge of electrosprayed water nanodroplets: a molecular dynamics study.
AB  - Aqueous nanodroplets that contain excess charge carriers play a central role
      during the electrospray ionization (ESI) process. An interesting question
      concerns the charge carrier location in these systems. In analogy to the behavior
      of metallic conductors, it is often assumed that excess ions are confined to a
      thin layer on the droplet surface. However, it is unclear whether simple
      electrostatic arguments adequately reflect the nanodroplet behavior. In
      particular, most ions tend to be heavily solvated, such that placing them at the
      liquid/vapor interface would be enthalpically unfavorable. In this work,
      molecular dynamics simulations are used to study the properties of Na(+)
      containing water nanodroplets close to the Rayleigh limit. In apparent violation
      of the surface charge paradigm, it is found that the ions reside inside the
      droplet. Electrostatic mapping reveals that all of the excess charge is
      nonetheless located on the surface. This conundrum is resolved by considering the
      effects of orientational water polarization. Buried Na(+) ions cause large-scale
      dipole ordering that extends all the way to the droplet periphery. Here, the
      positive ends of water dipoles preferentially point into the vapor phase. These
      half-dipoles in the outermost droplet layers assume the role of surface charge,
      while solvation effectively neutralizes Na(+) ions in the interior. Overall, our
      data reaffirm the validity of the surface charge paradigm for ESI nanodroplets,
      albeit with the caveat that this paradigm does NOT require charge carriers (ions)
      to be located at the water/vapor interface.

PMID- 20698695
TI  - Enantioselective synthesis of axially chiral biaryls by the Pd-catalyzed Suzuki
      Miyaura reaction: substrate scope and quantum mechanical investigations.
AB  - We report efficient syntheses of axially chiral biaryl amides in yields ranging
      from 80-92%, and with enantioselectivity in the range 88-94% ee employing an
      asymmetric Suzuki-Miyaura process with Pd(OAc)(2) and KenPhos as ligand. These
      studies demonstrate that electron-rich and electron-deficient o-halobenzamides
      can be efficiently coupled with 2-methyl-1-naphthylboronic acid and 2-ethoxy-1
      naphthylboronic acid. The yields and selectivities of the reactions are
      independent of the nature of halogen substituent on the benzamide coupling
      partner. Our investigations demonstrate that axially chiral heterocyclic and
      biphenyl compounds can also be synthesized with this methodology. We also report
      computational studies used to determine the origin of stereoselectivity during
      the selectivity-determining reductive elimination step of the related coupling of
      tolyl boronic acid with naphthylphosphonate bromide that was reported in a
      previous publication (J. Am. Chem. Soc. 2000, 122, 12051-12052). These studies
      indicate that the stereoselectivity arises from a combination of weak -(C)H..O
      interactions as well as steric interactions between the tolyl and
      naphthylphosphonate addends in the transition state for C-C coupling.

PMID- 20698696
TI  - Self-assembly of hybrid dendrons into doubly segregated supramolecular polyhedral
      columns and vesicles.
AB  - The synthesis and structural analysis of supramolecular dendrimers self-assembled
      from 3 libraries containing 20 first-generation hybrid dendrons are reported.
      Combinations of benzyl ether, naphthyl methyl ether, and biphenyl methyl ether
      repeat units with different alkyl carboxylates at the apex of the dendron
      decreased its molecular solid angle to values that led to the discovery of a new
      mechanism of self-assembly. This new self-assembly mechanism generated a
      diversity of unprecedented supramolecular assemblies, including hollow and
      nonhollow singly or doubly segregated supramolecular columns and vesicles
      exhibiting polyhedral shapes. The polyhedral shape of the self-organized
      supramolecular dendrimers was demonstrated to be an intrinsic characteristic of
      all the doubly segregated structures. The self-assembly mechanism elucidated here
      provides access to new strategies that will be used to fabricate complex
      supramolecular organizations.

PMID- 20698698
TI  - Theoretical study of substituted PBPB dimers: structural analysis, tetraradical
      character, and excited states.
AB  - The radicaloid nature of para and meta 1,3-diborata-2,4-diphosphoniocyclobutane
      1,3-diyl doubly substituted benzene is assessed from several electronic structure
      perspectives. Orbital occupation numbers computed by perfect pairing (PP),
      complete active space SCF (CASSCF), and restricted active space double spin-flip
      (RAS-2SF) reveal the presence of less than one unpaired electron in the planar
      molecules. Thus, the surprising stability of the "para tetraradical" can be
      rationalized by its moderate extent of radical character. Estimation of the
      delocalization energy, low-lying excited states, and short and long-range
      magnetic coupling constants all indicate a rather weak interaction to occur
      between two singlet PBPB units. Communication between two triplet units was found
      to be negligible. Comparison between para and meta isomers confirms a distinctly
      larger communication via the pi framework for the former. However, this
      communication, which was recently proposed to be the main factor for the
      different behavior of meta and para isomers regarding their preferred geometries,
      was found to account for only one-third of their energy difference. The study
      shows the important contribution of steric and/or electronic effects of the bulky
      (i)Pr and (t)Bu substituents on P and B.

PMID- 20698699
TI  - Direct analysis of donor-acceptor distance and relationship to isotope effects
      and the force constant for barrier compression in enzymatic H-tunneling
      reactions.
AB  - The role of dynamical effects in enzyme catalysis is both complex and widely
      debated. Understanding how dynamics can influence the barrier to an enzyme
      catalyzed reaction requires the development of new methodologies and tools. In
      particular compressive dynamics-the focus of this study-may decrease both the
      height and width of a reaction barrier. By making targeted mutations in the
      active site of morphinone reductase we are able to alter the equilibrium of
      conformational states for the reactive complex in turn altering the donor
      acceptor (D-A) distance for H-transfer. The sub-A changes which we induce are
      monitored using novel spectroscopic and kinetic "rulers". This new way of
      detecting variation in D-A distance allows us to analyze trends between D-A
      distance and the force constant of a compressive dynamical mode. We find that as
      the D-A distance decreases, the force constant for a compressive mode increases.
      Further, we demonstrate that-contrary to current dogma-compression may not always
      cause the magnitude of the primary kinetic isotope effect to decrease.

PMID- 20698697
TI  - The complex role of multivalency in nanoparticles targeting the transferrin
      receptor for cancer therapies.
AB  - Transferrin receptor (TfR, CD71) has long been a therapeutic target due to its
      overexpression in many malignant tissues. In this study, PRINT() nanoparticles
      were conjugated with TfR ligands for targeted drug delivery. Cylindrical
      poly(ethylene glycol)-based PRINT nanoparticles (diameter (d) = 200 nm, height
      (h) = 200 nm) labeled with transferrin receptor antibody (NP-OKT9) or human
      transferrin (NP-hTf) showed highly specific TfR-mediated uptake by all human
      tumor cell lines tested, relative to negative controls (IgG1 for OKT9 or bovine
      transferrin (bTf) for hTf). The targeting efficiency was dependent on particle
      concentration, ligand density, dosing time, and cell surface receptor expression
      level. Interestingly, NP-OKT9 or NP-hTf showed little cytotoxicity on all solid
      tumor cell lines tested but were very toxic to Ramos B-cell lymphoma, whereas
      free OKT9 or hTf was not toxic. There was a strong correlation between TfR ligand
      density on the particle surface and cell viability and particle uptake. NP-OKT9
      and NP-hTf were internalized into acidic intracellular compartments but were not
      localized in EEA1-enriched early endosomes or lysosomes. Elevated caspase 3/7
      activity indicates activation of apoptosis pathways upon particle treatment.
      Supplementation of iron suppressed the toxicity of NP-OKT9 but not NP-hTf,
      suggesting different mechanisms by which NP-hTf and NP-OKT9 exerts cytotoxicity
      on Ramos cells. On the basis of such an observation, the complex role of
      multivalency in nanoparticles is discussed. In addition, our data clearly reveal
      that one must be careful in making claims of "lack of toxicity" when a targeting
      molecule is used on nanoparticles and also raise concerns for unanticipated off
      target effects when one is designing targeted chemotherapy nanodelivery agents.

PMID- 20698700
TI  - Interfacial water structure associated with phospholipid membranes studied by
      phase-sensitive vibrational sum frequency generation spectroscopy.
AB  - Phase-sensitive vibrational sum frequency generation is employed to investigate
      the water structure at phospholipid/water interfaces. Interfacial water molecules
      are oriented preferentially by the electrostatic potential imposed by the
      phospholipids and have, on average, their dipole pointing toward the phospholipid
      tails for all phospholipids studied, dipalmitoyl phosphocholine (DPPC),
      dipalmitoyl phosphoethanolamine (DPPE), dipalmitoyl phosphate (DPPA), dipalmitoyl
      phosphoglycerol (DPPG), and dipalmitoyl phospho-l-serine (DPPS). Zwitterionic
      DPPC and DPPE reveal weaker water orienting capability relative to net negative
      DPPA, DPPG, and DPPS. Binding of calcium cations to the lipid phosphate group
      reduces ordering of the water molecules.

PMID- 20698701
TI  - Reactivity of [1],[1]disilamolybdenocenophane toward zerovalent platinum
      complexes.
AB  - The results of studies of the reactivity of strained
      [1],[1]disilamolybdenocenophane toward zerovalent platinum complexes are
      reported. Whereas [Pt(PEt(3))(3)] underwent clean insertion into both Si-C(ispo)
      bonds of the twofold-bridged molybdenocene, the reaction with the
      tricyclohexylphosphine analogue is considerably more complex. Thus, treatment of
      the molybdenum compound with 2 equiv of [Pt(PCy(3))(2)] results in a trinuclear
      cluster. To gain insight into the mechanistic aspects, the reaction was performed
      in a 1:1 stoichiometry. Multinuclear NMR spectroscopy revealed the presence of
      different species in solution. Two constitutional isomers were identified by X
      ray diffraction analyses, one presumably depicting an intermediate in the
      formation of the trinuclear cluster. The predominant isomer in solution was
      identified as the product of C-H oxidative addition to the platinum phosphine
      fragment. Its solid-state structure displays an unusual coordination mode of
      platinum, and structural parameters suggest the formulation as the sigma-complex
      of a Mo-Si bond.

PMID- 20698703
TI  - Six different assemblies from one building block: two-dimensional crystallization
      of an amide amphiphile.
AB  - A C(s)-symmetric amide amphiphile containing a C(18) alkyl chain exists in at
      least six crystalline phases at the liquid/solid interface; several of these
      phases display regularly arranged nanoscopic voids. Structural analysis of each
      phase reveals that highly symmetric and/or complex patterns arise through
      adopting various aggregates via noncovalent interactions, several of which are
      mediated by the unique hydrogen-bonding properties of the primary amide. The
      formation of each phase is interpreted in the context of the kinetic and
      thermodynamic behaviors, with some phases showing concentration-dependent
      stabilities, while others are purely kinetic in origin. This investigation
      contributes to understanding the factors that give rise to solid form diversity
      in two- and three-dimensional crystallization.

PMID- 20698702
TI  - Total synthesis of sporolide B and 9-epi-sporolide B.
AB  - The total synthesis of the structurally unique secondary metabolite sporolide B
      (1b) is described. The total synthesis of 1b was developed on the basis of
      preliminary studies that revealed the reactivity of an appropriate o-quinone as a
      diene system toward a number of indene derivatives as dienophiles, first in
      intermolecular and thence intramolecular settings. Thus, substrates were devised
      (37 and 75) that underwent exquisite intramolecular [4+2] cycloaddition reactions
      under thermal conditions to provide primitive sporolide-type structures that were
      subsequently elaborated to a sporolide model system, 9-epi-sporolide B, and 1b.
      The requisite indene o-quinone precursor 75 was synthesized through a ruthenium
      catalyzed [2+2+2] cycloaddition reaction between a propargylic alcohol and a
      chloroacetylenic cyclopentenyne, followed by elaboration and silver-promoted
      oxidation of the resulting chloroindene derivative. In addition to the total
      synthesis of 1b, this work demonstrated, for the first time, the power of the
      intramolecular hetero [4+2] cycloaddition reaction in the total synthesis of
      complex molecules and the application of the ruthenium-catalyzed [2+2+2]
      cycloaddition reaction to highly substituted indene systems possessing a chlorine
      residue on the aromatic nucleus.

PMID- 20698704
TI  - Seed-mediated synthesis of Ag nanocubes with controllable edge lengths in the
      range of 30-200 nm and comparison of their optical properties.
AB  - Silver nanocubes with edge lengths controllable in the range of 30-200 nm were
      synthesized using an approach based on seeded growth. The keys to the success of
      this synthesis are the use of single-crystal Ag seeds to direct the growth and
      the use of AgNO(3) as a precursor to elemental Ag, where the byproduct HNO(3) can
      block both the homogeneous nucleation and evolution of single-crystal seeds into
      twinned nanoparticles. Either spherical (in the shape of a cuboctahedron) or
      cubic seeds could be employed for this growth process. The edge length of the
      resultant Ag nanocubes can be readily controlled by varying the amount of Ag
      seeds used, the amount of AgNO(3) added, or both. For the first time, we could
      obtain Ag nanocubes with uniform edge lengths controllable in the range of 30-200
      nm and then compare their localized surface plasmon resonance and surface
      enhanced Raman scattering properties.

PMID- 20698705
TI  - Enantiomerically pure trans-beta-lactams from alpha-amino acids via compact
      fluorescent light (CFL) continuous-flow photolysis.
AB  - Photolysis of alpha-diazo-N-methoxy-N-methyl (Weinreb) beta-ketoamides derived
      from enantiomerically pure (EP) alpha-amino acids affords the corresponding EP
      beta-lactams via an intramolecular Wolff rearrangement. The photochemistry is
      promoted with either standard UV irradiation or through the use of a 100 W
      compact fluorescent light; the latter affords a safe and environmentally friendly
      alternative to standard photolysis conditions. A continuous-flow photochemical
      reactor made from inexpensive laboratory equipment reduced reaction times and was
      amenable to scale-up. The diastereoselectivity (cis or trans) of the product beta
      lactams has been shown to vary from modest to nearly complete. An extremely
      facile, atom-economical method for the epimerization of the product mixture to
      the trans isomer, which is generally highly crystalline, has been developed.
      Evidence for C3 epimerization of Weinreb amide structures via a nonbasic, purely
      thermal route is presented. Subsequent transformations of both the Weinreb amide
      at C3 (beta-lactam numbering) and the amino acid side chain at C4 are well
      tolerated, allowing for a versatile approach to diverse beta-lactam structures.
      The technology is showcased in the synthesis of a common intermediate used toward
      several carbapenem-derived structures starting from unfunctionalized aspartic
      acid.

PMID- 20698709
TI  - Curious about pesticide action.
AB  - The safe and effective use of pesticides requires knowledge of their mode of
      action in pests and adverse effects in nontarget organisms coupled with an
      understanding of their metabolic activation and detoxification. The author and
      his laboratory colleagues were privileged to observe, participate in, and
      sometimes influence these developments for the past six decades. This review
      considers contributions of the Berkeley and Madison laboratories to understanding
      insecticides acting at voltage-gated sodium and GABA-gated chloride channels and
      the nicotinic receptor and at serine hydrolases and other targets as well as the
      action of insecticide synergists and selected herbicides and fungicides. Some of
      the discoveries gave new probes, radioligands, photoaffinity labeling reagents,
      and understanding of reactive intermediates that changed the course of pesticide
      investigations and related areas of science. The importance of coupling mode of
      action with metabolism and design with serendipity is illustrated with a wide
      variety of chemotypes.

PMID- 20698710
TI  - One-step method for generating PEG-like plasma polymer gradients: chemical
      characterization and analysis of protein interactions.
AB  - In this work we report a one-step method for the fabrication of poly(ethylene
      glycol) PEG-like chemical gradients, which were deposited via continuous wave
      radio frequency glow discharge plasma polymerization of diethylene glycol
      dimethyl ether (DG). A knife edge top electrode was used to produce the gradient
      coatings at plasma load powers of 5 and 30 W. The chemistry across the gradients
      was analyzed using a number of complementary techniques including spatially
      resolved synchrotron source grazing incidence FTIR microspectroscopy, X-ray
      photoelectron spectroscopy (XPS) and synchrotron source near edge X-ray
      absorption fine structure (NEXAFS) spectroscopy. Gradients deposited at lower
      load power retained a higher degree of monomer like functionality as did the
      central region directly underneath the knife edge electrode of each gradient
      film. Surface derivatization experiments were employed to investigate the
      concentration of residual ether units in the films. In addition, surface
      derivatization was used to investigate the reactivity of the gradient films
      toward primary amine groups in a graft copolymer of poly (L-lysine) and
      poly(ethylene glycol) (PLL-g-PEG copolymer) which was correlated to residual
      aldehyde, ketone and carboxylic acid functionalities within the films. The
      protein adsorption characteristics of the gradients were analyzed using three
      proteins of varying size and charge. Protein adsorption varied and was dependent
      on the chemistry and the physical properties (such as size and charge) of the
      proteins. A correlation between the concentration of ether functionality and the
      protein fouling characteristics along the gradient films was observed. The
      gradient coating technique developed in this work allows for the efficient and
      high-throughput study of biomaterial gradient coating interactions.

PMID- 20698711
TI  - Growth kinetic processes of AlN molecules on the Al-polar surface of AlN.
AB  - We studied growth kinetic processes of AlN molecules on the Al-polar surface of
      AlN using ab initio and Monte Carlo simulations. Molecular processes were
      presented and analyzed during the nucleation, ripening, and coalescence stages.
      The results show that the nucleus number decreases as temperature rises due to
      the increasing diffusion of the molecules. By analyzing the growth time
      dependence of average cluster size, interface-limited Ostwald ripening is found
      to be the main ripening mechanism when the temperature is lower than 1773 K. As
      cluster-corner crossing diffusion is limited, the growth is fractal-like
      extension, and the coalescence is achieved through adhesion of clusters, leading
      to a generally continuous morphology with some vacancies and closure failures,
      which is in good agreement with our experimental results. Moreover,
      coverage/temperature kinetic phase diagrams under different deposition rates are
      presented (from 0.025 to 0.1 ML/s). Our finding suggests that a temperature
      higher than 1800 K is crucial for growth of an ideal atomic-scale Al-polar AlN
      surface.

PMID- 20698712
TI  - Catalytic asymmetric synthesis of the endo-6-aryl-8-oxabicyclo[3.2.1]oct-3-en-2
      one natural product from Ligusticum chuanxing via 1,3-dipolar cycloaddition of a
      formyl-derived carbonyl ylide using Rh2(S-TCPTTL)4.
AB  - The reaction of a six-membered cyclic formyl-carbonyl ylide derived from alpha
      diazo-beta-ketoester with phenylacetylene derivatives under the catalysis of
      dirhodium(II) tetrakis[N-tetrachlorophthaloyl-(S)-tert-leucinate], Rh(2)(S
      TCPTTL)(4), provides cycloadducts containing an 8-oxabicyclo[3.2.1]octane ring
      system in up to 97% ee. This represents the first example of an enantioselective
      1,3-dipolar cycloaddition of a cyclic formyl-carbonyl ylide. Using this catalytic
      process, an asymmetric synthesis of endo-6-aryl-8-oxabicyclo[3.2.1]oct-3-en-2-one
      natural product 1 from Ligusticum chuanxing Hort. has been achieved.

PMID- 20698713
TI  - The effect of intermolecular hydrogen bonding on the fluorescence of a bimetallic
      platinum complex.
AB  - The bimetallic platinum complexes are known as unique building blocks and
      arewidely utilized in the coordination-driven self-assembly of functionalized
      supramolecular metallacycles. Hence, photophysical study of the bimetallic
      platinum complexes will be very helpful for the understanding on the optical
      properties and further applications of coordination-driven self-assembled
      supramolecular metallacycles. Herein, we report steady-state and time-resolved
      spectroscopic experiments as well as quantum chemistry calculations to
      investigate the significant intermolecular hydrogen bonding effects on the
      intramolecular charge transfer (ICT) fluorescence of a bimetallic platinum
      compound 4,4'-bis(trans-Pt(PEt(3))(2)OTf)benzophenone 3 in solution. We
      demonstrated that the fluorescent state of compound 3 can be assigned as a metal
      to-ligand charge transfer (MLCT) state. Moreover, it was observed that the
      formation of intermolecular hydrogen bonds can effectively lengthen the
      fluorescence lifetime of 3 in alcoholic solvents compared with that in hexane
      solvent. At the same time, the electronically excited states of 3 in solution are
      definitely changed by intermolecular hydrogen bonding interactions. As a
      consequence, we propose a new fluorescence modulation mechanism by hydrogen
      bonding to explain different fluorescence emissions of 3 in hydrogen-bonding
      solvents and nonhydrogen-bonding solvents.

PMID- 20698714
TI  - Content of botulinum neurotoxin in Botox(r)/Vistabel(r), Dysport(r)/Azzalure(r),
      and Xeomin(r)/Bocouture(r).
AB  - BACKGROUND: Botulinum neurotoxin type A (BoNT/A) is the active substance in
      preparations used for the highly effective treatment of neurologic disorders such
      as cervical dystonia, blepharospasm, or spasticity, as well as other indications
      such as axillary and palmar hyperhidrosis, and urologic disorders. OBJECTIVE: To
      determine the amount of BoNT/A protein present in pharmaceutical preparations of
      Botox(r), Dysport(r), and Xeomin(r), which are identical with Vistabel(r),
      Azzalure(r), and Bocouture(r), respectively. METHODS: Rabbit and guinea pig
      antibodies raised against the 150 kD BoNT/A neurotoxin purified from Clostridium
      botulinum type A, strain ATCC 3502 ('Hall strain'), were used in a sensitive
      sandwich ELISA to determine the overall mean concentration of the 150 kD
      neurotoxin present in four batches of Botox(r) (C2344C3, C2384C3, C2419, and
      C2385), two batches of Dysport(r) (678F and 689X) and three batches of Xeomin(r)
      (61,111, 70,604, and 81,208). The specific neurotoxin potency, defined as the
      potency or biologic activity (units) per mass of neurotoxin protein (ng), was
      calculated based on the overall mean concentration of BoNT/A neurotoxin. RESULTS:
      Overall, the mean concentration of BoNT/A neurotoxin in Botox(r) was 0.73 ng per
      100 unit vial (coefficient of variation [CV] = 3.5%), 3.24 ng per 500 unit vial
      of Dysport(r), corresponding to 0.65 ng in 100 units (CV = 11.4%), and 0.44 ng
      per 100 unit vial of Xeomin(r) (CV = 1.9%). The specific potency of the 150 kD
      BoNT/A neurotoxin was calculated as 137 units/ng for Botox(r), 154 units/ng
      Dysport(r), and 227 units/ng Xeomin(r). CONCLUSIONS: The current study has shown
      that of the three products, Xeomin(r) contains the highest specific neurotoxin
      activity, followed by Dysport(r), with Botox(r) having the lowest specific
      activity. This result suggests that Xeomin(r) contains only active neurotoxin in
      contrast with Botox(r), which is likely to contain additional denatured/inactive
      neurotoxin.

PMID- 20698715
TI  - Visual field protective effect of Erigeron breviscapus (vant.) Hand. Mazz.
      extract on glaucoma with controlled intraocular pressure: a randomized, double
      blind, clinical trial.
AB  - OBJECTIVE: To evaluate the visual field protective effect of Erigeron breviscapus
      (vant.) Hand. Mazz. (EBHM) extract on glaucoma with controlled intraocular
      pressure (IOP). METHODS: Forty patients (40 eyes) with primary open-angle
      glaucoma, visual field defects and a postsurgical IOP of <18 mmHg were enrolled.
      The EBHM and placebo tablets were given orally according to the randomized and
      double-blind principle. Two tablets (of either EBHM or placebo) were taken three
      times a day for a period of 6 months. Patients were examined every 2 months after
      treatment commenced. At the end of the study, the results were given to the drug
      manufacturer. RESULTS: All patients completed the prospective, randomized, double
      blind, clinical trial. No obvious adverse effects were found in patients during
      the treatment period. In the placebo group, no significant difference was found
      in mean defect (MD) or mean sensitivity (MS) between the values at pre-treatment
      and after 2, 4, and 6 months of treatment. After 6 months of EBHM treatment, the
      MD was significantly decreased and the MS was significantly increased compared
      with pre-treatment (p < 0.05). In the patients with moderate and late glaucoma,
      the MD was significantly decreased and the MS was significantly increased after
      2, 4, and 6 months of EBHM treatment compared with pre-treatment. CONCLUSION:
      EBHM extract may have a partial protective effect on the visual field of glaucoma
      patients with controlled IOP. Further studies are needed to determine the safety
      and effectiveness of long-term EBHM treatment.

PMID- 20698716
TI  - Metabolism and disposition of tribendimidine and its metabolites in healthy
      Chinese volunteers.
AB  - BACKGROUND: Tribendimidine is a new anthelmintic agent synthesized by Chinese
      scientists. It is a broad spectrum agent with high activity against parasites.
      However, its disposition and metabolism remain unknown. OBJECTIVE: To investigate
      the metabolism, disposition, and metabolites of tribendimidine in healthy human
      volunteers. METHODS: Twelve healthy Chinese volunteers were chosen after clinical
      assessment of health status and laboratory tests. They received single oral doses
      of tribendimidine 400 mg enteric-coated tablets. Blood and urine samples were
      collected at scheduled timepoints. Samples were qualitatively and quantitatively
      analyzed by liquid chromatography-mass spectrometric (LC-MS) and high performance
      liquid chromatography (HPLC) methods, respectively. RESULTS: Tribendimidine was
      rapidly and completely broken down to p-(1-dimethylamino ethylimino) aniline
      (dADT) and terephthalaldehyde (TPAL). Furthermore, dADT was partially transformed
      to acetylated dADT, and TPAL completely transformed to terephalic acid (TPAC).
      The main pharmacokinetic parameters (+/- SD) of dADT were as follows: elimination
      half life (t(1/2)) 4.74 +/- 1.80 h; elimination rate constant (K(e)) 0.16 +/-
      0.06 h-1; apparent volume of distribution (Vd/F) 12.23 +/- 8.69 L * kg(-1);
      apparent total clearance of the drug from plasma (CL/F) 1.63 +/- 0.58 L * h(-1) *
      kg(-1); area under the plasma concentration-time curve (AUC) from time 0 to time
      24 hours (AUC(24)) 4.29 +/- 1.88 MUg * mL(-1) * h; AUC from time zero to infinity
      (AUC(infinity)) 4.45 +/- 1.81 MUg * mL(-1) * h; maximum plasma drug concentration
      (C(max)) 0.64 +/- 0.27 MUg * mL(-1); and time to C(max) (t(max)) 4.20 +/- 0.71 h.
      A total of 35.28% dADT and 28.50% TPAC were excreted through the urine within 24
      hours after tribendimidine administration. CONCLUSION: These results reveal the
      disposition, metabolism, and main metabolites of tribendimidine in healthy
      Chinese volunteers.

PMID- 20698717
TI  - Is it possible to accurately determine content of botulinum neurotoxin type A in
      drug products?

PMID- 20698718
TI  - Closed gateways--can neuroprotectants shield the retina in glaucoma?
AB  - Neuroprotection for glaucoma is a therapeutic approach that aims to prevent optic
      nerve damage or cell death. An appropriate drug that reaches an adequate
      concentration across the blood retinal barrier is expected to shield the retina
      in glaucoma. Several in vitro and in vivo attempts in experimental models
      indicate the possibility of successful neuroprotection. However, clinical trials
      might not show the same level of neuroprotection as a result of subtherapeutic
      concentrations of the drug in the eye. The study by Zhong et al. in this issue of
      Drugs in R&D could not attribute the observed improvement in visual field indices
      to any one of the individual active constituents of Erigeron breviscapus (vant.)
      Hand. Mazz. (EBHM). One of the major constituents of EBHM is scutellarin, which
      is known to have poor oral bioavailability and an unclear ability to penetrate
      inside the eye. Therefore, before recognizing EBHM as a neuroprotectant in
      glaucoma for further clinical studies and practice, its active constituents and
      their pharmacokinetics (systemic as well as ocular) need to be explored.

PMID- 20698719
TI  - Ipilimumab.
AB  - Ipilimumab (BMS734016; MDX 101; MDX-010; MDX-CTLA-4; MDX-CTLA4) is an anti-CTLA-4
      monoclonal antibody, which is in development by Medarex Inc. and Bristol-Myers
      Squibb as treatment for malignant melanoma, prostate cancer, lymphoma, and lung
      cancer. It is currently in phase III development for the melanoma and prostate
      cancer indications, and phase II for lymphoma and non-small cell lung cancer in
      the US and other areas of the world. This review discusses the key development
      milestones and therapeutic trials on this drug to date.

PMID- 20698720
TI  - Linifanib.
AB  - Linifanib (A 741439; A-741439; A741439; ABT-869; ABT869; RG3635) is an orally
      active multi-targeted receptor tyrosine kinase inhibitor for the treatment of
      various cancers. It was being developed by Roche but development has now reverted
      to Abbott. The compound is designed to inhibit vascular endothelial growth factor
      and platelet-derived growth factor receptors. It is in phase III development for
      liver cancer and phase II development for non-small cell lung cancer, breast
      cancer, and colorectal cancer in the US, the EU and other areas of the world.
      This review discusses the key development milestones and therapeutic trials of
      this drug.

PMID- 20698721
TI  - Tremelimumab.
AB  - Tremelimumab (CP 675206; CP-675; CP-675,206; CP-675206; Ticilimumab) is a fully
      human IgG2 anitbody, which is directed against human cytotoxic T lymphocyte
      associated antigen 4 (CTLA4). It is being developed by Pfizer for the treatment
      of various cancers. It is currently in worldwide phase III development for
      malignant melanoma, phase II development for colorectal cancer, gastrointestinal
      cancer, gynecological cancer, and non-small cell lung cancer in the US and other
      countries, and is also being investigated for prostate, breast, and pancreatic
      cancer in various countries. This review discusses the key development milestones
      and therapeutic trials of this drug.

PMID- 20698724
TI  - Thorough cardiac QTc interval conductance assessment of a novel oral tranexamic
      acid treatment for heavy menstrual bleeding.
AB  - OBJECTIVE: To assess the effect of a novel oral tranexamic acid treatment on
      cardiac repolarization in a randomized, double-blind, positive- and placebo
      controlled, four-treatment single-dose cross-over inpatient study. METHODS: QTc
      interval and drug exposure relationship analyses were performed using triplicate
      digital electrocardiographs (ECGs) collected from 12-lead Holter monitors from
      healthy females (n = 48) with plasma drug concentrations and pharmacokinetics
      simultaneously evaluated over 24 h post-dose. Therapeutic (1.3 g) and
      supratherapeutic (3.9 g) tranexamic acid modified immediate-release doses, a
      positive-control 0.4 g moxifloxacin dose, and a placebo-control were administered
      at each period. RESULTS: All post-dose, time-matched, baseline-adjusted, mean
      QTcF (Fridericia's heart rate correction, QT/RR(1/3)) treatment-placebo
      differences (DeltaDeltaQTcF), were less than 5 milliseconds (ms) for the 1.3 g
      and 3.9 g tranexamic acid doses. Upper limits of the 95% confidence interval (CI)
      for all tranexamic acid-placebo DeltaDeltaQTcF doses were < 10 ms for all time
      points. Lower limits of the 95% CI for the positive-control (moxifloxacin
      placebo) DeltaDeltaQTcF were > 5 ms at multiple time points demonstrating assay
      sensitivity. No correlation between tranexamic acid plasma concentrations and
      adjusted QTc intervals was observed. A positive linear relationship was observed
      for moxifloxacin (p < 0.01). CONCLUSION: Cardiac repolarization is not influenced
      by tranexamic acid at the doses studied.

PMID- 20698725
TI  - Recent advances in antiretroviral drugs.
AB  - IMPORTANCE OF THE FIELD: Acquired immunodeficiency syndrome (AIDS) is one of the
      leading causes of death worldwide. Although the combination therapies of highly
      active antiretroviral therapy (HAART) have significantly contributed to
      virological suppression, improved immune function and quality of life, issues
      such as tolerability, drug-drug interactions and cross-resistance amongst members
      of a particular drug class still pose a significant barrier to long-term
      successful treatment. There is a constant need for newer anti HIV drugs with
      increased potency and improved pharmacokinetic properties either in the existing
      classes or drugs from new classes that target several new steps in HIV
      replication cycle. AREAS COVERED IN THIS REVIEW: The authors have discussed newer
      antiretroviral drugs belonging to second-generation nucleoside analog reverse
      transcriptase inhibitors (amdoxovir, elvucitabine, apricitabine, racivir), non
      nucleoside analog reverse transcriptase inhibitors (etravirine, rilpivirine),
      protease inhibitors (darunavir, tipranavir) as well as emerging new classes,
      i.e., fusion inhibitors (enfuvirtide, sifuvirtide), CCR5 inhibitors (maraviroc,
      vicriviroc, PRO 140, PRO 542), CD4-receptor inhibitors (ibalizumab), integrase
      inhibitors (raltegravir, elvitegravir, GSK-1349572), maturation inhibitors
      (bevirimat), cobicistat (pharmacoenhancer), lens epithelium-derived growth factor
      inhibitors and capsid assembly inhibitors. WHAT THE READER WILL GAIN: The reader
      will gain an understanding of the mechanism of action, mechanism of resistance,
      stages of development and important clinical trials related to the newer
      antiretroviral drugs and future potential of these drugs. TAKE HOME MESSAGE: The
      initial clinical trial data of these newer drugs are very encouraging for the
      long-term successful control of HIV in both treatment-naive and treatment
      experienced patients.

PMID- 20698726
TI  - Telbivudine: an effective anti-HBV drug for chronic hepatitis B patients with
      early on-treatment responses.
AB  - IMPORTANCE OF THE FIELD: Hepatitis B virus (HBV) is a significant
      hepatocarcinogen. HBV replication is a major cause for the development of
      hepatocellular carcinoma (HCC). Past studies have documented that lamivudine
      (LAM) therapy deterred progression to cirrhosis and HCC. This risk reduction is
      attributed to effective viral suppression. There is a need for as many effective
      anti-HBV drugs as possible. AREAS COVERED IN THIS REVIEW: Telbivudine, the fourth
      FDA-approved oral antiviral drug, is highly potent for viral suppression for HBV.
      It is more potent than LAM and adefovir; its therapeutic response is superior to
      that of LAM in both HBeAg-positive and -negative patients, and it produces higher
      HBeAg seroconversion in patients with baseline ALT > or = 2 times normal.
      Telbivudine has a resistance rate lower than that of LAM and higher than that of
      entecavir or tenofovir. WHAT THE READER WILL GAIN: There is a specific group of
      patients who are likely to achieve good therapeutic response with telbivudine.
      TAKE HOME MESSAGE: Patients with low baseline HBV DNA combined with negative HBV
      DNA at week 24 obtain good therapeutic results with telbivudine. Therefore,
      selecting patients who meet the above conditions is important.

PMID- 20698728
TI  - How to promote exercise in primary care.

PMID- 20698729
TI  - Prevalence of cancer alarm symptoms: a population-based cross-sectional study.
AB  - OBJECTIVE: To estimate the prevalence of alarm symptoms for breast, colorectal,
      urinary tract, and lung cancer in the general population. DESIGN: Cross-sectional
      questionnaire survey. SETTING: The former County of Funen, Denmark, with 480,000
      inhabitants. PARTICIPANTS: A total of 13,777 randomly selected persons aged 20
      years and older. MAIN OUTCOME MEASURES: Prevalence estimates of having
      experienced cancer alarm symptoms during the past 12 months: a lump in the
      breast, blood in bowel movements, blood in urine, or coughing for more than six
      weeks. The number of alarm symptoms experienced within the past 12 months was
      also calculated. RESULTS: With a response rate of 69%, 3.3% of responders (95% CI
      2.9% to 3.7%) reported a lump in their breast, 5.7% (5.2% to 6.3%) reported blood
      in bowel movements, 2.2% (1.9% to 2.5%) reported blood in urine, and 6.5% (6.1%
      to 7.5%) reported coughing for more than six weeks within the past 12 months.
      Overall, 15.3% (95% confidence interval 14.3% to 16.3%) of the females and 12.7%
      (11.6% to 13.7%) of the males reported having experienced at least one cancer
      alarm symptom within the past 12 months. CONCLUSION: Alarm symptoms of breast,
      colorectal, urinary tract, and lung cancer are common in the general population
      and approximately 15% of the population have experienced at least one of these
      cancer alarm symptom within the past 12 months.

PMID- 20698730
TI  - Associations between successful palliative trajectories, place of death and GP
      involvement.
AB  - OBJECTIVE: General practitioner (GP) involvement may be instrumental in obtaining
      successful palliative cancer trajectories. The aim of the study was to examine
      associations between bereaved relatives' evaluation of palliative cancer
      trajectories, place of death, and GP involvement. DESIGN: Population-based, cross
      sectional combined register and questionnaire study. SETTING: The former Aarhus
      County, Denmark. SUBJECTS: Questionnaire data on GPs' palliative efforts and
      relatives' evaluations of the palliative trajectories were obtained for 153 cases
      of deceased cancer patients. MAIN OUTCOME MEASURES: A successful palliative
      trajectory as evaluated retrospectively by the relatives. RESULTS: Successful
      palliative trajectories were statistically significantly associated with home
      death (PR 1.48 (95% CI 1.04; 2.12)). No significant associations were identified
      between the evaluations of the palliative trajectory at home and GP involvement.
      "Relative living with patient" (PR 1.75 (95% CI: 0.87; 3.53)) and "GP having
      contact with relatives" (PR 1.69 (95% CI 0.55; 5.19)) were not significantly
      associated, but this may be due to the poor number of cases included in the final
      analysis. CONCLUSION: This study indicates that home death is positively
      associated with a higher likelihood that bereaved relatives will evaluate the
      palliative trajectory at home as successful. No specific GP services that were
      statistically significantly associated with higher satisfaction among relatives
      could be identified, but contact between GPs and relatives seems important and
      the impact needs further investigation.

PMID- 20698731
TI  - Diastolic dysfunction is associated with sedentary leisure time physical activity
      and smoking in females only.
AB  - OBJECTIVES: Left ventricular diastolic dysfunction with preserved systolic
      function (DD-PSF) is associated with an increased risk of morbidity and
      mortality. Population-based surveys studying the associations between DD-PSF and
      lifestyle-associated risk factors, such as leisure time physical activity (LTPA)
      and smoking, are scarce. Thus, the aims were to explore the associations between
      DD-PSF and LTPA and smoking, employing optimal echocardiographic techniques.
      DESIGN: Cross-sectional study conducted from 2001 to 2003. SETTING: The study was
      conducted in a random sample of a rural Swedish population. SUBJECTS: Men and
      women of 30-75 years of age were consecutively invited for conventional
      echocardiography and tissue velocity imaging (n = 1149). Structured
      questionnaires and physical examinations were conducted using standardized
      methods. MAIN OUTCOME MEASURES: DD-PSF was defined according to the European
      Society of Cardiology criteria excluding subjects with ejection fraction < 45%,
      or a self-reported history of heart failure. RESULTS: Complete information was
      available in 500 men and 538 women. In a multivariate model, DD-PSF was
      independently associated with sedentary LTPA and smoking in females; sedentary
      LTPA odds ratio (OR) 2.91, 95% confidence interval (CI) 1.02 to 8.27, and smoking
      OR 3.42, 95% CI 1.35 to 8.64. The probability of identifying DD-PSF in females
      with a sedentary LTPA was 37% and increased to 80% if they also had hypertension
      and were obese. CONCLUSIONS: Sedentary LTPA and smoking are independently
      associated with DD-PSF in females. Identification of a sedentary lifestyle in
      females increases the probability of diagnosing DD-PSF.

PMID- 20698732
TI  - Prevention and treatment of no-reflow.
AB  - No-reflow phenomenon occurs frequently during primary percutaneous coronary
      intervention for ST-segment elevation myocardial infarction and it has a strong
      negative impact on outcome. Prevention of no-reflow has to be defined as any
      attempt to prevent its occurrence prior to or during the recanalization
      procedure. Strategy of prevention may be pharmacological or device based. Among
      drugs, abciximab is indicated by European Society of Cardiology (ESC) guidelines
      for prevention of no-reflow (class of recommendation IIa and level of evidence
      B). Among devices used for preventing no-reflow, manual thrombus aspiration only
      has been associated with a reduction of no-reflow and lower mortality at follow
      up and is currently indicated in the ESC guidelines (class IIa of recommendation
      and level B of evidence). Treatment of no-reflow has to be defined as any attempt
      to treat its occurrence after coronary recanalization. Strategy of treatment may
      be pharmacological or device based. Adenosine and verapamil are indicated by ESC
      guidelines for treatment of no-reflow (class of recommendation IIb and level of
      evidence B and C, respectively). Serial assessment of myocardial perfusion showed
      that in up to 50% of patients no-reflow is spontaneously reversible. This finding
      may open new scenarios, as mechanisms of reversibility may become future
      therapeutic targets.

PMID- 20698733
TI  - Kinetics of procalcitonin in cardiogenic shock and in septic shock. Preliminary
      data.
AB  - BACKGROUND: In cardiac acute patients, data on procalcitonin (PCT) are
      controversial and the clinical interpretation of absolute PCT values represents a
      major challenge since they may be influenced by several factors. No data are so
      far available on the dynamics of PCT levels in patients with cardiogenic shock.
      AIMS: to evaluate the serum evolution of PCT during intensive cardiac care unit
      (ICCU) staying in a group of 24 patients with cardiogenic shock (CS) following ST
      elevation myocardial infarction (STEMI) submitted to primary percutaneous
      intervention (PCI) with no laboratory or clinical sign of infection. Furthermore
      we assessed the kinetics of PCT in a series of 24 patients with septic shock.
      RESULTS: In septic shock, no significant difference was detectable in PCT
      kinetics between survivors (R2 = 0.90; P = 0.051) and non-survivors (R2 = 0.63; P
      = 0.204). In cardiogenic shock, survivors exhibited a significant reduction in
      PCT values (R2 = 0.94; P = 0.032) while non survivors did not (R2 = 0.68; P =
      0.178). CONCLUSIONS: differently from septic shock, cardiogenic shock following
      STEMI was associated with heterogeneous patterns of temporal PCT variations since
      only patients who survived exhibited a significant PCT reduction during ICCU
      stay. Our findings support the contention that the 'dynamic' approach may be more
      reliable that the static one especially in cardiogenic shock.

PMID- 20698734
TI  - The relationship between hypertension and salt intake in Turkish population:
      SALTURK study.
AB  - This population-based epidemiological study was aimed to evaluate the daily salt
      intake and its relation to blood pressure in a representative group of Turkish
      population. The enrolled normotensive and hypertensive individuals (n = 1970)
      completed a questionnaire including demographics, dietary habits, hypertension
      awareness and drug usage. Blood pressure was measured and to estimate salt
      consumption, 24-h urine samples were collected. The daily urinary sodium
      excretion was 308.3 +/- 143.1 mmol/day, equal to a salt intake of 18.01 g/day.
      Salt intake was higher in obese participants, rural residents, participants with
      lower education levels and elderly. A positive linear correlation between salt
      intake and systolic and diastolic blood pressures was demonstrated (r = 0.450, p
      = 0.020; r = 0.406, p = 0.041; respectively), and each 100 mmol/day of salt
      intake resulted in 5.8 and 3.8 mmHg increase in systolic and diastolic blood
      pressures, respectively. Salt intake and systolic blood pressure was
      significantly correlated in normal weight individuals (r = 0.257, p < 0.01). The
      Turkish population consumes a great amount of salt; salt intake and blood
      pressure was positively correlated. Efforts in sodium restriction are therefore
      crucial in the management of hypertension as part of national and global health
      policies.

PMID- 20698735
TI  - The COMT and DRD3 genes interacted in bipolar I but not bipolar II disorder.
AB  - OBJECTIVES. Clarifying the association between bipolar I and bipolar II disorders
      at the genetic level is essential for improving our understanding of them. In
      this study, we evaluated the hypothesis that the dopaminergic polymorphisms are
      risk factors for bipolar disorders. We examined the association between the
      catechol-O-methyltransferase (COMT) Val158Met and dopamine D3 receptor (DRD3)
      Ser9Gly polymorphisms and bipolar I and II disorders, as well as possible
      interactions between these genes. METHODS. Seven hundred and eleven participants
      were recruited: 205 with bipolar I, 270 with bipolar II, and 236 healthy
      controls. The genotypes of the COMT Val158Met and DRD3 Ser9Gly polymorphisms were
      determined using polymerase chain reactions plus restriction fragment length
      polymorphism analysis. RESULTS. Logistic regression analyses showed a
      statistically significant main effect for the Met/Met genotype of the COMT
      Val158Met polymorphism (P=0.032) and a significant interaction effect for the
      Met/Met genotype of the COMT Val158Met and Ser/Ser genotypes of the DRD3 Ser9Gly
      polymorphism (P=0.001) predicted bipolar I patients. However, there was no
      association between the COMT Val158Met or DRD3 Ser9Gly and bipolar II.
      CONCLUSIONS. We provide initial evidence that the COMT Val158Met and DRD3 Ser9Gly
      genotypes interact in bipolar I and bipolar II disorders and that bipolar I and
      bipolar II are genetically distinct.

PMID- 20698736
TI  - Association between pregnancy complications and small-for-gestational-age birth
      weight defined by customized fetal growth standard versus a population-based
      standard.
AB  - OBJECTIVE: To derive coefficients for developing a customized growth chart for a
      Mid-Western US population, and to estimate the association between pregnancy
      outcomes and smallness for gestational age (SGA) defined by the customized growth
      chart compared with a population-based growth chart for the USA. METHOD: A
      retrospective cohort study of an ultrasound database using 54,433 pregnancies
      meeting inclusion criteria was conducted. Coefficients for customized centiles
      were derived using 42,277 pregnancies and compared with those obtained from other
      populations. Two adverse outcome indicators were defined (greater than 7 day stay
      in the neonatal unit and stillbirth [SB]), and the risk for each outcome was
      calculated for the groups of pregnancies defined as SGA by the population
      standard and SGA by the customized standard using 12,456 pregnancies for the
      validation sample. RESULTS: The growth potential expressed as weight at 40 weeks
      in this population was 3524 g (standard error: 402 g). In the validation
      population, 4055 cases of SGA were identified using both population and
      customized standards. The cases additionally identified as SGA by the customized
      method had a significantly increased risk of each of the adverse outcome
      categories. The sensitivity and specificity of those identified as SGA by
      customized method only for detecting pregnancies at risk for SB was 32.7% (95%
      confidence interval [CI] 27.0-38.8%) and 95.1% (95% CI: 94.7-95.0%) versus 0.8%
      (95% CI 0.1-2.7%) and 98.0% (95% CI 97.8-98.2%)for those identified by only the
      population-based method, respectively. CONCLUSION: SGA defined by customized
      growth potential is able to identify substantially more pregnancies at a risk for
      adverse outcome than the currently used national standard for fetal growth.

PMID- 20698737
TI  - The frequency and risk factors of funisitis and histologic chorioamnionitis in
      pregnant women at term who delivered after the spontaneous onset of labor.
AB  - OBJECTIVE: To examine the frequency and risk factors of funisitis and histologic
      chorioamnionitis in the placentas of term pregnant women who delivered after the
      spontaneous onset of labor. METHODS: The frequency of funisitis and histologic
      chorioamnionitis was examined in consecutive pregnant women at term with
      singleton pregnancies who delivered after the spontaneous onset of labor.
      Nonparametric statistics were used for data analysis. RESULTS: (1) The frequency
      of funisitis and histologic chorioamnionitis was 6.7% (88/1316) and 23.6%
      (310/1316), respectively; (2) Patients with funisitis had significantly higher
      rates of nulliparity, regional analgesia, operative vaginal delivery, longer
      duration of labor and rupture of membranes (ROM), and higher gestational age and
      birthweight than those without funisitis (p < 0.05 for each); (3) Patients with
      histologic chorioamnionitis had significantly higher rates of nulliparity,
      oxytocin augmentation, regional analgesia, cesarean section or operative vaginal
      delivery, longer duration of labor and ROM, and higher gestational age and
      birthweight than those without histologic chorioamnionitis (p < 0.05 for each);
      (4) Multiple logistic regression analysis indicated that the longer the duration
      of labor, the higher the risk of funisitis, and that nulliparity and the duration
      of labor significantly increased the odds of histologic chorioamnionitis (p <
      0.05 for each). CONCLUSION: The longer the duration of labor, the higher the risk
      of funisitis and histologic chorioamnionitis in pregnant women at term who
      delivered after the spontaneous onset of labor.

PMID- 20698738
TI  - Mitochondria in the striatum of subjects with schizophrenia.
AB  - OBJECTIVES: Schizophrenia is a severe mental illness that manifests pathology in
      many brain regions, including the striatum. Among the abnormalities in
      schizophrenia are those related to mitochondria. The present study sought to
      determine whether the number of mitochondria was affected at the level of the
      synapse. METHODS: Human postmortem striatum from schizophrenia subjects and
      controls was examined at the ultrastructural level. The density of mitochondria
      and synapses were tabulated using stereology. RESULTS: There were similar overall
      numbers of mitochondria in the caudate nucleus and putamen of schizophrenia
      subjects vs. controls, but a differential distribution of existing mitochondria.
      Schizophrenia subjects had 26?30% fewer mitochondria per synapse compared to
      controls. This may contribute to the pathophysiology of the illness, may be a
      medication effect, or an adaptive response to normalize the high number of
      striatal synapses we have previously found. The higher density of mitochondria in
      dendrites in the caudate nucleus in certain subgroups of schizophrenia vs.
      controls (>34%) may be related to more synaptic inputs. CONCLUSIONS: The role of
      mitochondria in the various symptoms of schizophrenia is still unclear. A
      comparison of schizophrenia subjects with differing symptoms or treatment
      response might shed light on whether differences in mitochondrial density are
      abnormal or adaptive.

PMID- 20698739
TI  - Contactless respiratory and heart rate monitoring: validation of an innovative
      tool.
AB  - PRIMARY OBJECTIVE: To assess the accuracy of the EverOnTM piezoelectric sensor
      based contactless heart rate and respiration rate monitoring system. METHODS:
      Measurements of the EverOnTM and reference devices were performed in a sleep lab
      and an intensive care unit (ICU) setting. One minute measurements by both the
      reference device and the EverOnTM were averaged and compared. Accuracy was
      defined in accordance with industry criteria. RESULTS: Respiration rate (RR)
      accuracy in the 41 children and 16 adults evaluated in the sleep lab was 93.1%
      and 90.6% respectively, and heart rate (HR) accuracy was 94.4% and 91.5%
      respectively. For the 42 ICU patients RR accuracy was 82.0% and 75% (versus end
      tidal CO(2) and manual respectively), while accuracy of HR was 94.0%. The
      EverOnTM was found to be superior to the impedance technique in measuring RR.
      CONCLUSIONS: The system described was found to be accurate in accordance with
      regulatory and industry criteria.

PMID- 20698740
TI  - Liver fibrosis in hepatitis C patients of Pakistani versus Scandinavian origin.
AB  - OBJECTIVE: The aim of this study was to examine the significance of native
      country for the stage of liver fibrosis in a population of HCV patients of
      Pakistani or Scandinavian origin living in Oslo. PATIENTS AND METHODS: We
      included 122 consecutive HCV patients at two hepatitis clinics in Oslo, 73 of
      Scandinavian and 49 of Pakistani origin. Inclusion criteria were being HCV RNA
      positive, treatment naive and having an adequate liver biopsy. The biopsies were
      scored according to the Metavir index, which scores fibrosis on a scale from 0 to
      4 and necroinflammatory activity on a scale from 0 to 3. Steatosis was scored
      according to the percentage of hepatocytes having lipid droplets in their
      cytoplasm. Demographical, clinical, virological and biochemical data for the two
      groups were registered from the patient files. RESULTS: The median age was 43 and
      42 years and 53% and 51% were male among the Scandinavian and Pakistani patients,
      respectively. Among the patients of Pakistani origin 18/49 (37%) had bridging
      fibrosis (F3) or cirrhosis (F4) compared to 11/73 (15%) Scandinavian patients
      (p=0.006). The mean fibrosis score was 1.78 in the Pakistani and 0.82 in the
      Scandinavian group (p<0.001). The mean necroinflammatory activity score was 1.22
      and 0.78 in the Pakistanis and Scandinavians, respectively (p<0.001). In the
      Pakistani group more patients had >=5% steatosis (59% vs. 33%; p=0.004), diabetes
      mellitus (24% vs. 0%; p<0.001), overweight (46% vs. 34%; p=0.232), genotype 3
      (84% vs. 42%; p<0.001) and ALT and AST levels above the reference range (84% vs.
      64%; p=0.020 and 88% vs. 68%; p=0.014) compared to the Scandinavian. Multivariate
      regression analyses identified age >=40 years (OR 10.13; 95% CI 2.65-39.12) and
      genotype 3 (OR 5.02; 95% CI 1.19-21.17) as independent predictors of bridging
      fibrosis/cirrhosis. CONCLUSIONS: In HCV patients of similar age, those of
      Pakistani origin had more advanced liver disease than those of Scandinavian
      origin. Possible explanations are longer duration of the infection and higher
      occurrence of diabetes mellitus, liver steatosis and genotype 3 in the Pakistani
      group.

PMID- 20698741
TI  - Studies on the synergistic effects of extremely low-frequency magnetic fields and
      the endocrine-disrupting compound atrazine on the thyroid gland.
AB  - PURPOSE: The aim of this study was to examine the effect of extremely low
      frequency magnetic fields (MF) and the endocrine-disrupting compound atrazine,
      each separately, on the thyroid gland of juvenile-peripubertal rats, and to
      investigate the possible synergistic effect of these two factors combined.
      MATERIALS AND METHODS: The study was performed on male Wistar rats from postnatal
      day 23-53. Animals were divided into six groups: (1) 4 h/day exposure to MF (50
      Hz, 100-300 MUT, 54-160 V/m), (2) 20 mg/kg of body weight (bw) of atrazine, (3)
      200 mg/kg bw of atrazine, (4) MF with 20 mg/kg bw of atrazine (5) MF with 200
      mg/kg bw of atrazine, and (6) control. RESULTS: Light and electron microscopic
      studies demonstrated no significant alterations in the thyroid structure between
      the treated groups and the control. Significant outcomes were found regarding the
      volume density of thyroid follicles and the connective tissue between the MF
      exposed group when compared to both atrazine treatments and the combined
      treatments. The high dose of atrazine significantly affected the number of mast
      cells compared to the control. CONCLUSIONS: No synergistic effect of the MF and
      the endocrine-disrupting compound atrazine on the thyroid gland has been found.
      The specific histological alterations of the thyroid parenchyma observed in some
      treated groups require further investigation.

PMID- 20698742
TI  - Effects of mobile phone use on brain tissue from the rat and a possible
      protective role of vitamin C - a preliminary study.
AB  - PURPOSE: To evaluate effects of mobile phone use on brain tissue and a possible
      protective role of vitamin C. MATERIALS AND METHODS: Forty female rats were
      divided into four groups randomly (Control, mobile phone, mobile phone plus
      vitamin C and, vitamin C alone). The mobile phone group was exposed to a mobile
      phone signal (900 MHz), the mobile phone plus vitamin C group was exposed to a
      mobile phone signal (900 MHz) and treated with vitamin C administered orally (per
      os). The vitamin C group was also treated with vitamin C per os for four weeks.
      Then, the animals were sacrificed and brain tissues were dissected to be used in
      the analyses of malondialdehyde (MDA), antioxidant potential (AOP), superoxide
      dismutase, catalase (CAT), glutathione peroxidase (GSH-Px), xanthine oxidase,
      adenosine deaminase (ADA) and 5'nucleotidase (5'-NT). RESULTS: Mobile phone use
      caused an inhibition in 5'-NT and CAT activities as compared to the control
      group. GSH-Px activity and the MDA level were also found to be reduced in the
      mobile phone group but not significantly. Vitamin C caused a significant increase
      in the activity of GSH-Px and non-significant increase in the activities of 5'
      NT, ADA and CAT enzymes. CONCLUSION: Our results suggest that vitamin C may play
      a protective role against detrimental effects of mobile phone radiation in brain
      tissue.

PMID- 20698743
TI  - Effect of selective COX-2 inhibitor, celecoxib on adjuvant-induced arthritis
      model in irradiated rats.
AB  - PURPOSE: The potential value of celecoxib was compared to a standard non
      steroidal anti-inflammatory drug (NSAID), diclofenac in the adjuvant-induced
      arthritis (AIA) model in rats as a model of chronic inflammation under the
      influence of ionising radiation. MATERIAL AND METHODS: Various inflammatory
      mediators and biochemical parameters were measured in the arthritic rats under
      the influence of ionising radiation. RESULTS: Exposure of the animals to a
      radiation dose of 2 Gy before inoculation of the adjuvant led to a marked
      increase in the paw volume reaching ca. 70% more than that in non-irradiated ones
      as well as a significant increase in the levels of interleukin-6 (IL-6),
      interleukin-1beta (IL-1beta), tumour necrosis factor-alpha (TNF-alpha),
      prostaglandin E2 (PGE2) as an index of cyclooxygenase-2 (COX-2) activity,
      thromboxane B2 (TXB2) as an index of cyclooxygenase-1 (COX-1) activity and plasma
      level of malondialdehyde (MDA). The blood glutathione (GSH) level was not
      affected by the dose of irradiation used while superoxidedismutase (SOD) activity
      was reduced. Treatment with celecoxib in a dose of 5 mg/kg was effective in
      decreasing the elevated levels of IL-6, IL-1beta, TNF-alpha, PGE2 whereas it
      lacked any effect on TXB2 level since it had hardly any effect on COX-1 enzyme.
      Both drugs at the selected dose levels showed no effect on level of MDA, GSH and
      SOD activity. CONCLUSION: Irradiation of animals caused a marked change in the
      inflammatory response in AIA model of inflammation. Both celecoxib and diclofenac
      were nearly equipotent in suppressing the inflammatory response in both normal
      and irradiated rats. Accordingly, since the inhibition of COX-1 by traditional
      NSAID is thought to have undesirable side-effects on proliferating tissues, it
      would seem preferable to use selective COX-2 inhibitors to limit such deleterious
      effect.

PMID- 20698744
TI  - Purple sweet potato pigments protect murine thymocytes from 60Co gamma-ray
      induced mitochondria-mediated apoptosis.
AB  - PURPOSE: Purple sweet potato (PSP) pigments have been widely accepted as
      antioxidants but their radioprotective effect still remains unclear. In this
      study we investigated the effect of PSP pigments on 60Co gamma-ray-induced
      mitochondria-mediated apoptosis in murine thymocytes. MATERIALS AND METHODS: The
      murine thymocytes were pretreated by PSP pigments before exposure to 4 Gy 60Co
      gamma-rays. Flow cytometry analysis was used to measure apoptotic cells and
      mitochondrial membrane potential. Reactive oxygen species (ROS) were detected
      using 2',7',-dichlorofluorescein diacetate (DCFH-DA) probe and the activity of
      antioxidant enzymes was tested by biochemical assay after irradiation. Cytochrome
      c, caspase-3 and poly ADP-ribose polymerase (PARP) were measured by Western
      blotting. RESULTS: After treatment with PSP pigments and exposure to 4 Gy
      radiation the apoptosis of thymocytes was reduced and the mitochondrial
      transmembrane potential was maintained compared to control cells. In the presence
      of PSP pigments, ROS were reduced and the activities of glutathione peroxidase
      (GSH-px) and superoxide dismutase (SOD) were protected and in some cases
      increased. All the pro-apoptotic proteins (cytochrome oxidase, caspase 3 and
      PARP) decreased in PSP pigments pretreated thymocytes compared to irradiated
      cells in the absence of PSP pigments. CONCLUSIONS: Pre-treatment with PSP
      pigments significantly inhibited 60Co gamma-ray-induced mitochondria-mediated
      apoptosis. This radioprotective effect might be related to ROS scavenging, the
      enhancement of the activity of antioxidant enzymes, the maintenance of
      mitochondrial transmembrane potential, and the sequential inhibition of
      cytochrome c release and downstream caspase and PARP cleavage.

PMID- 20698746
TI  - Nontoxic genetic engineering of mesenchymal stem cells using serum-compatible
      pullulan-spermine/DNA anioplexes.
AB  - Genetic modification of stem cells could be applied to initiate/enhance their
      secretion of therapeutic molecules, alter their biological properties, or label
      them for in vivo tracking. We recently developed a negatively charged gene
      carrier ("anioplex") based on pullulan-spermine, a conjugate prepared from a
      natural polysaccharide and polyamine. In rat mesenchymal stem cells (MSCs),
      anioplex-derived reporter gene activity was comparable to or exceeded that
      obtained using a commercial cationic lipid reagent. Transfection in the growth
      medium with 15% serum and antibiotics was approximately sevenfold more effective
      than in serum-free conditions. Cytotoxicity was essentially indiscernible after
      24 h of anioplex transfection with 20 MUg/mL DNA, in contrast to cationic lipid
      transfection that resulted in 40%-60% death of target MSCs. Anioplex-derived
      reporter gene activity persisted throughout the entire 3-week study, with post
      transfection MSCs appearing to maintain osteogenic, adipogenic, and chondrogenic
      multipotency. In particular, chondrogenic pellet formation of differentiating
      human MSCs was significantly inhibited after lipofection but not after
      aniofection, which further indicates the biological inertness of pullulan
      spermine/DNA anioplexes. Collectively, these data introduce a straightforward
      technology for genetic engineering of adult stem/progenitor cells under
      physiological niche-like conditions. Moreover, reporter gene activity was
      observed in rat spinal cords after minimally invasive intrathecal implantation,
      suggesting effective engraftment of donor MSCs. It is therefore plausible that
      anioplex-transfected MSCs or other stem/progenitor cells with autologous
      potential could be applied to disorders such as neurotrauma or neuropathic pain
      that involve the spinal cord and brain.

PMID- 20698747
TI  - Agitation can induce differentiation of human pluripotent stem cells in
      microcarrier cultures.
AB  - One of the factors that can impact human embryonic stem cell expansion in stirred
      microcarrier culture reactors is mechanical stress caused by agitation.
      Therefore, we have investigated the effects of agitation on human embryonic stem
      cell growth and expression of pluripotent markers. Agitation of HES-2 cell line
      in microcarrier cultures in stirred spinner and agitated six-well plates did not
      affect expression of pluripotent markers, cell viability, and cell doubling times
      even after seven passages. However, HES-3 cell line was found to be shear
      sensitive, showing downregulation of three pluripotent markers Oct-4, mAb 84, and
      Tra-1-60, and lower cell densities in agitated as compared with static cultures,
      even after one passage. Cell viability was unaffected. The HES-3-agitated
      cultures showed increased expression of genes and proteins of the three germ
      layers. We were unable to prevent loss of pluripotent markers or restore doubling
      times in agitated HES-3 microcarrier cultures by addition of five different known
      cell protective polymers. In addition, the human induced pluripotent cell line
      IMR90 was also shown to differentiate in agitated conditions. These results
      indicate that the effect of agitation on cell growth and differentiation is cell
      line specific. We assume that the changes in the growth and differentiation of
      the agitation-sensitive (HES-3) cell line do not result from the effect of shear
      stress directly on cell viability, but rather by signaling effects that influence
      the cells to differentiate resulting in slower growth.

PMID- 20698748
TI  - Cost effectiveness of escitalopram versus SNRIs in second-step treatment of major
      depressive disorder in Sweden.
AB  - OBJECTIVES: Escitalopram is the S-enantiomer of citalopram and is the most
      discriminating of the selective serotonin reuptake inhibitors (SSRI). The aim of
      the current analysis was to assess the cost effectiveness of escitalopram versus
      the serotonin norepinephrine reuptake inhibitors (SNRI) duloxetine and generic
      venlafaxine as second-step treatment of major depressive disorder. METHODS: The
      analysis was based on a decision analytic model. Effectiveness outcomes were
      quality-adjusted life-years (QALYs) and remission rates; cost outcomes were
      direct medical costs, including impact of treating adverse events, and indirect
      costs associated with lost productivity. The analysis was performed from the
      societal perspective in Sweden over a 6-month timeframe. RESULTS: Estimated
      remission rates showed an incremental effectiveness in favour of escitalopram of
      16.4 percentage points compared with both SNRI comparators. The escitalopram
      strategy was associated with a 0.025 increase in QALYs. Sensitivity analyses
      demonstrated that the model is robust and that escitalopram remains a cost
      effective option when considering future predicted price reductions of generic
      venlafaxine. LIMITATIONS: The main limitation in this study was the lack of data
      available for second-step treatment. The remission rates, which are a key input
      to the model, were obtained from a relatively small sample of patients on second
      step treatment and there are no published relapse rates for second-step
      treatment. The model also assumed that there was no difference in the adverse
      event (AE) rates between treatments after the first 8 weeks. CONCLUSIONS: This
      cost-effectiveness analysis indicates that, at a willingness-to-pay threshold of
      L30,000, escitalopram is the most cost-effective second-step treatment option for
      MDD in Sweden in over 85% cases compared with both venlafaxine and with
      duloxetine. Benefits for escitalopram included both increased effectiveness and
      reduced overall costs. The major contributing costs were those associated with
      productivity loss. The model was shown to have internal validity and robustness
      through the use of stochastic simulations and sensitivity analyses, which were
      conducted around the key efficacy parameters.

PMID- 20698750
TI  - The effectiveness of oracin in enhancing the cytotoxicity of doxorubicin through
      the inhibition of doxorubicin deactivation in breast cancer MCF7 cells.
AB  - The maximal therapeutic doses of the cytostatic drug doxorubicin (DOX) are
      strictly limited by the development of systemic toxicity, especially
      cardiotoxicity. The inhibition of DOX-metabolizing enzymes within cancer cells is
      possible strategy to improve DOX efficacy. In breast cancer cells (MCF7), DOX is
      effectively deactivated by carbonyl reduction. The aim of the present study was
      to test whether isoquinoline derivative oracin (ORC) is able to inhibit DOX
      reductases and to enhance DOX cytotoxic efficacy. The kinetics studies of DOX
      reduction in MCF7 cytosolic fractions were evaluated using high-performance
      liquid chromatography. The cytotoxicity of DOX, ORC, and DOX+ORC combinations was
      assayed using cell-viability tests and caspases activities and monitored using
      xCELLigence System for real-time cell analysis. ORC significantly inhibited DOX
      reduction in MCF7 cytosol. Competitive inhibition was found. The viability was
      significantly lower in cells treated with ORC+DOX combinations in comparison to
      cells treated with DOX alone. Significant enhancement of DOX cytotoxicity was
      achieved already with 0.5 uM ORC. DOX together with ORC was able to kill about
      55% cells more than DOX alone. ORC significantly increases DOX efficacy in MCF7
      cells probably due to the inhibition of DOX reductases.

PMID- 20698751
TI  - The association between symptomatic asthma and neurobehavioral comorbidities
      among children.
AB  - BACKGROUND: Asthma affects millions of children in the United States. The extent
      to which asthma and other medical conditions coexist, however, is largely
      unknown. OBJECTIVE: This study aimed to determine associations between
      symptomatic asthma and neurobehavioral comorbidities among children in rural
      United States. METHODS: This cross-sectional study used data from 406
      parents/caregivers of children aged 16 or younger, who completed survey
      questionnaires assessing their child's health status. Symptomatic asthma was
      defined as parents'/caregivers' report of physician diagnosed asthma and presence
      of night-time asthma symptoms in their children. The dependent variables were
      parents'/caregivers' reported comorbidities in children. RESULTS: Symptomatic
      asthma was present in 9% of the sample. Approximately 26% parents/caregivers
      reported their child had one or more mental health problems and 13% reported one
      or more neurological problems. In multivariable logistic regression analyses, a
      statistically nonsignificant 50% elevated odds of one or more mental health
      problems were observed for children with symptomatic asthma (adjusted odds ratio
      [OR] = 1.5, 95% confidence interval [CI] = 0.6-3.5). Of the individual
      comorbidities included in the mental health construct, more than 2-fold elevated
      odds of anxiety problems (adjusted OR = 2.6, 95% CI = 0.8-8.6) and attentional
      problems (adjusted OR = 2.4, 95% CI = 1.0-5.8) were observed for symptomatic
      asthma. The odds of reporting one or more neurological problems were 4-fold
      elevated (adjusted OR = 4.0, 95% CI = 1.6-10.0) for symptomatic asthma. Of the
      individual comorbidities included in the neurological construct a significantly
      elevated odds of hearing impairment or deafness was observed among children with
      symptomatic asthma (adjusted OR = 8.2, 95% CI = 1.5-45.3) as compared to the no
      asthma/no symptoms reference group. CONCLUSION: These data suggest significant
      associations between symptomatic asthma and neurological comorbidities.

PMID- 20698749
TI  - Human adipose-derived stromal cells stimulate autogenous skeletal repair via
      paracrine Hedgehog signaling with calvarial osteoblasts.
AB  - Human adipose-derived stromal cells (hASCs) have the proven capacity to ossify
      skeletal defects. The mechanisms whereby hASCs stimulate bone repair are not
      fully understood. In this study, we examined the potential for hASCs to stimulate
      autogenous repair of a mouse calvarial defect. Immunofluoresence, osteogenic
      stains, and surface electron microscopy were used to demonstrate osteogenic
      differentiation of hASCs. hASCs were engrafted into 4 mm calvarial defects in
      athymic mice using an osteoconductive scaffold. Analysis included microcomputed
      tomography, histology, in situ hybridization, and quantitative real-time
      polymerase chain reaction. Next, the in vitro interaction between hASCs and mouse
      calvarial osteoblasts (mOBs) was assessed by the conditioned medium and coculture
      assays. The medium was supplemented with Hedgehog signaling modifiers, including
      recombinant N-terminal Sonic hedgehog, smoothened agonist, and cyclopamine.
      Finally, cyclopamine was delivered in vivo to hASC-engrafted defects. Significant
      calvarial healing was observed among hASC-engrafted defects compared with control
      groups (no treatment or scaffold alone) (*P<0.05). hASCs showed evidence of
      stimulation of host mouse osteogenesis, including (1) increased expression of
      bone markers at the defect edge by in situ hybridization, and (2) increased host
      osteogenic gene expression by species-specific quantitative real-time polymerase
      chain reaction. Using the conditioned medium or coculture assays, hASCs
      stimulated mOB osteogenic differentiation, accompanied by Hedgehog signaling
      activation. N-terminal Sonic hedgehog or smoothened agonist replicated, while
      cyclopamine reversed, the pro-osteogenic effect of the conditioned medium on
      mOBs. Finally, cyclopamine injection arrested bone formation in vivo. hASCs heal
      critical-sized mouse calvarial defects, this is, at least in part, via
      stimulation of autogenous healing of the host defect. Our studies suggest that
      hASC-derived Hedgehog signaling may play a paracrine role in skeletal repair.

PMID- 20698753
TI  - Reactive oxygen/nitrogen species and the myocardial cell homeostasis: an
      ambiguous relationship.
AB  - The totality of functional cardiomyocytes and an intact cardiac progenitor cell
      pool are key players in the myocardial cell homeostasis. Perturbation of either
      one may compromise the structural and functional integrity of the heart and lead
      to heart failure. Reactive oxygen/nitrogen species (ROS/RNS) are important
      regulators of cardiomyocyte viability; more recently, the interrelation between
      ROS and progenitor cell behavior and fate has moved into the spotlight.
      Increasing evidence suggests not only that ROS participate in the regulation of
      cardiac progenitor cell survival but also that they likewise affect their
      functional properties in terms of self-proliferation and differentiation. The
      apparent dichotomy of ROS/RNS effects with their adaptive and regulatory
      character on the one hand and their maladaptive and damaging features on the
      other pose a great challenge in view of the therapeutic exploitation of their
      role in the regulation of the myocardial cell homeostasis. In this article,
      mechanisms and potential significance of ROS/RNS action in the regulation of the
      myocardial cell homeostasis, in particular with respect to the preservation of
      viable cardiomyocytes and the maintenance of a functional cardiac progenitor cell
      pool, will be discussed.

PMID- 20698752
TI  - Sinorhizobium meliloti requires a cobalamin-dependent ribonucleotide reductase
      for symbiosis with its plant host.
AB  - Vitamin B(12) (cobalamin) is a critical cofactor for animals and protists, yet
      its biosynthesis is limited to prokaryotes. We previously showed that the
      symbiotic nitrogen-fixing alphaproteobacterium Sinorhizobium meliloti requires
      cobalamin to establish a symbiotic relationship with its plant host, Medicago
      sativa (alfalfa). Here, the specific requirement for cobalamin in the S. meliloti
      alfalfa symbiosis was investigated. Of the three known cobalamin-dependent
      enzymes in S. meliloti, the methylmalonyl CoA mutase (BhbA) does not affect
      symbiosis, whereas disruption of the metH gene encoding the cobalamin-dependent
      methionine synthase causes a significant defect in symbiosis. Expression of the
      cobalamin-independent methionine synthase MetE alleviates this symbiotic defect,
      indicating that the requirement for methionine synthesis does not reflect a need
      for the cobalamin-dependent enzyme. To investigate the function of the cobalamin
      dependent ribonucleotide reductase (RNR) encoded by nrdJ, S. meliloti was
      engineered to express an Escherichia coli cobalamin-independent (class Ia) RNR
      instead of nrdJ. This strain is severely defective in symbiosis. Electron
      micrographs show that these cells can penetrate alfalfa nodules but are unable to
      differentiate into nitrogen-fixing bacteroids and, instead, are lysed in the
      plant cytoplasm. Flow cytometry analysis indicates that these bacteria are
      largely unable to undergo endoreduplication. These phenotypes may be due either
      to the inactivation of the class Ia RNR by reactive oxygen species, inadequate
      oxygen availability in the nodule, or both. These results show that the critical
      role of the cobalamin-dependent RNR for survival of S. meliloti in its plant host
      can account for the considerable resources that S. meliloti dedicates to
      cobalamin biosynthesis.

PMID- 20698755
TI  - Plant height affects Fusarium crown rot severity in wheat.
AB  - Effects of plant height on Fusarium crown rot (FCR) disease severity were
      investigated using 12 pairs of near-isogenic lines (NILs) for six different
      reduced height (Rht) genes in wheat. The dwarf isolines all gave better FCR
      resistance when compared with their respective tall counterparts, although the
      Rht genes involved in these NILs are located on several different chromosomes.
      Treating plants with exogenous gibberellin increased FCR severity as well as
      seedling lengths in all of the isolines tested. Analysis of the expression of
      several defense genes with known correlation with resistance to FCR pathogens
      between the Rht isolines following FCR inoculation indicated that the better
      resistance of the dwarf isolines was not due to enhanced defense gene induction.
      These results suggested that the difference in FCR severity between the tall and
      dwarf isolines is likely due to their height difference per se or to some
      physiological and structural consequences of reduced height. Thus, caution should
      be taken when considering to exploit any FCR locus located near a height gene.

PMID- 20698754
TI  - Transplantation of human adipose tissue-derived multilineage progenitor cells
      reduces serum cholesterol in hyperlipidemic Watanabe rabbits.
AB  - Familial hypercholesterolemia (FH) is an autosomal codominant disease
      characterized by high concentrations of proatherogenic lipoproteins and premature
      atherosclerosis secondary to low-density lipoprotein (LDL) receptor deficiency.
      We examined a novel cell therapy strategy for the treatment of FH in the Watanabe
      heritable hyperlipidemic (WHHL) rabbit, an animal model for homozygous FH. We
      delivered human adipose tissue-derived multilineage progenitor cells (hADMPCs)
      via portal vein and followed by immunosuppressive regimen to avoid xenogenic
      rejection. Transplantation of hADMPCs resulted in significant reductions in total
      cholesterol, and the reductions were observed within 4 weeks and maintained for
      12 weeks. (125)I-LDL turnover study showed that the rate of LDL clearance was
      significantly higher in the WHHL rabbits with transplanted hADMPCs than those
      without transplanted. After transplantation hADMPCs were localized in the portal
      triad, subsequently integrated into the hepatic parenchyma. The integrated cells
      expressed human albumin, human alpha-1-antitrypsin, human Factor IX, human LDL
      receptors, and human bile salt export pump, indicating that the transplanted
      hADMPCs resided, survived, and showed hepatocytic differentiation in vivo and
      lowered serum cholesterol in the WHHL rabbits. These results suggested that
      hADMPC transplantation could correct the metabolic defects and be a novel therapy
      for inherited liver diseases.

PMID- 20698756
TI  - Molecular variation among isolates of Verticillium dahliae and polymerase chain
      reaction-based differentiation of races.
AB  - Verticillium dahliae is a soilborne fungal pathogen that causes vascular wilt in
      a variety of economically important crops worldwide. There are two races of V.
      dahliae that infect tomato and lettuce. Although race-1-specific resistance has
      been identified in both tomato and lettuce, no resistant sources are available
      for race 2. Molecular analyses were employed to characterize the genetic
      variability and race structure of 101 isolates of V. dahliae from a variety of
      hosts, mainly from central and coastal California, and 10 isolates exotic to this
      area. Analyses of the 16 simple sequence repeat (SSR) markers illustrated that
      tomato subpopulations from central California were distinct relative to the
      marigold subpopulations. In contrast, cotton and olive isolates showed admixture
      with tomato isolates. Analyses of both the ribosomal DNA intergenic spacer
      regions and SSR markers revealed high genetic variability among isolates but were
      unable to delineate races of V. dahliae. However, a polymerase chain reaction
      (PCR) assay was applied to amplify a race-1-specific amplicon from the isolates
      in many hosts from different geographic areas, and was coupled with virulence
      assays for validation of the data. Results of the PCR assay showed 100%
      concordance with the virulence assay to differentiate race 1 from race 2 of 48
      isolates from tomato. The results indicate that the PCR assay can be applied to
      differentiate the two races to support our related aim of breeding host
      resistance, and further reveal insights into the distribution of races in tomato
      and lettuce cropping systems in California.

PMID- 20698757
TI  - Docosahexaenoic acid prevents white matter damage after spinal cord injury.
AB  - We have previously shown that the omega-3 fatty acid docosahexaenoic acid (DHA)
      significantly improves several histological and behavioral measures after spinal
      cord injury (SCI). White matter damage plays a key role in neurological outcome
      following SCI. Therefore, we examined the effects of the acute intravenous (IV)
      administration of DHA (250 nmol/kg) 30 min after thoracic compression SCI in
      rats, alone or in combination with a DHA-enriched diet (400 mg/kg/d, administered
      for 6 weeks post-injury), on white matter pathology. By 1 week post-injury, the
      acute IV DHA injection led to significantly reduced axonal dysfunction, as
      indicated by accumulation of beta-amyloid precursor protein (-55% compared to
      vehicle-injected controls) in the dorsal columns. The loss of cytoskeletal
      proteins following SCI was also significantly reduced. There were 43% and 73%
      more axons immunoreactive for non-phosphorylated 200-kD neurofilament in the
      ventral white matter and ventrolateral white matter, respectively, in animals
      receiving DHA injections than vehicle-injected rats. The acute DHA treatment also
      led to a significant improvement in microtubule-associated protein-2
      immunoreactivity. By 6 weeks, damage to myelin and serotonergic fibers was also
      reduced. For some of the parameters measured, the combination of DHA injection
      and DHA-enriched diet led to greater neuroprotection than DHA injection alone.
      These findings demonstrate the therapeutic potential of DHA in SCI, and clearly
      indicate that this fatty acid confers significant protection to the white matter.

PMID- 20698758
TI  - Vascular endothelial growth factor and spinal cord injury pain.
AB  - Vascular endothelial growth factor (VEGF)-A mRNA was previously identified as one
      of the significantly upregulated transcripts in spinal cord injured tissue from
      adult rats that developed allodynia. To characterize the role of VEGF-A in the
      development of pain in spinal cord injury (SCI), we analyzed mechanical allodynia
      in SCI rats that were treated with either vehicle, VEGF-A isoform 165
      (VEGF(165)), or neutralizing VEGF(165)-specific antibody. We have observed that
      exogenous administration of VEGF(165) increased both the number of SCI rats that
      develop persistent mechanical allodynia, and the level of hypersensitivity to
      mechanical stimuli. Our analysis identified excessive and aberrant growth of
      myelinated axons in dorsal horns and dorsal columns of chronically injured spinal
      cords as possible mechanisms for both SCI pain and VEGF(165)-induced
      amplification of SCI pain, suggesting that elevated endogenous VEGF(165) may have
      a role in the development of allodynia after SCI. However, the neutralizing
      VEGF(165) antibody showed no effect on allodynia or axonal sprouting after SCI.
      It is possible that another endogenous VEGF isoform activates the same signaling
      pathway as the exogenously-administered 165 isoform and contributes to SCI pain.
      Our transcriptional analysis revealed that endogenous VEGF(188) is likely to be
      the isoform involved in the development of allodynia after SCI. To the best of
      our knowledge, this is the first study to suggest a possible link between VEGF,
      nonspecific sprouting of myelinated axons, and mechanical allodynia following
      SCI.

PMID- 20698759
TI  - Development of autonomic dysreflexia after spinal cord injury is associated with
      a lack of serotonergic axons in the intermediolateral cell column.
AB  - Autonomic dysreflexia consistently develops in patients and in rats after severe
      upper thoracic spinal cord injury (SCI) as a result of exaggerated spinal
      sympathetic excitation. In this study we induced episodic hypertension in rats
      after varying degrees of SCI severity to investigate the contribution of
      serotonergic bulbospinal axons to the development of autonomic dysreflexia after
      SCI. Female Wistar rats (250-300 g) were used in all experiments in the following
      groups: (1) uninjured, (2) clip compression at T4 of 20, 35, or 50 g, (3) spinal
      cord transection at T4, and (4) intrathecal 5,7-dihydroxytryptamine creatinine
      sulfate (5,7-DHT). Immunohistochemistry for choline acetyl transferase and
      serotonin (5-HT) was performed on T8-T12 spinal segments to identify sympathetic
      preganglionic neurons, and to assess 5-HT-containing axons in the
      intermediolateral cell column (IMLC), respectively. Testing for autonomic
      dysreflexia was conducted by measuring mean arterial pressure (MAP) at rest and
      after colon distension-induced hypertension. We observed that the magnitude of
      the pressor response seen after colon distension correlated with SCI severity and
      density of 5-HT-immunoreactive axons in the IMLC. Intrathecal administration of
      the 5-HT(2A) agonist dimethoxy-4-iodamphetamine increased resting MAP and blocked
      colon distension-induced hypertension, whereas the 5-HT(2A) antagonist ketanserin
      decreased resting MAP and was permissive to the colon distension-induced pressor
      response in SCI rats. These results suggest that the SCI-induced loss of
      serotonergic inputs into the spinal cord IMLC is proportional to the pathogenesis
      of autonomic dysreflexia and hypotension seen after SCI. We thus conclude that
      sparing of serotonergic axons beyond a critical threshold preserves
      cardiovascular regulation and prevents the development of autonomic dysreflexia.

PMID- 20698761
TI  - Changes in the brain after intracerebral implantation of a lead pellet in the
      rat.
AB  - In gunshot wounds to the head, the bullet containing neurotoxic lead may remain
      in the brain after trauma, and brain damage is therefore anticipated. We
      developed an animal model incorporating a lead ball implanted in the brain, or a
      glass ball as a control, and analyzed histological and biochemical changes in the
      brain for 28 days after surgery. The concentration of lead in the brain increased
      with time after implantation of the lead ball, while lead was not detected in
      brains implanted with a glass ball. A number of changes were noted following
      implantation of the lead ball. The number of neutrophils increased significantly
      at 7-28 days, while the number of macrophages also increased significantly with
      time. The number of neurons was significantly decreased by 28 days, and apoptotic
      cells were identified at 14-28 days. Expression of genes encoding N-methyl-d
      aspartate receptors, which are related to cognitive function and help regulate
      apoptosis, was significantly suppressed at 7-21 days after implantation.
      Expression of metallothionein protein increased significantly with time.
      Metallothionein detoxifies lead and its overexpression is a known method of
      protection against lead neurotoxicity. These findings indicate that intracerebral
      lead induces neuronal degeneration that is attributable in part to the
      inflammation and apoptosis caused by leached lead. Although the severity of the
      brain damage primarily depends on the destructive effect of the moving bullet,
      the results of this study indicate that lead leaching from the residual bullet
      also damages the brain.

PMID- 20698760
TI  - Neuroproteomics: a biochemical means to discriminate the extent and modality of
      brain injury.
AB  - Diagnosis and treatment of stroke and traumatic brain injury remain significant
      health care challenges to society. Patient care stands to benefit from an
      improved understanding of the interactive biochemistry underlying neurotrauma
      pathobiology. In this study, we assessed the power of neuroproteomics to contrast
      biochemical responses following ischemic and traumatic brain injuries in the rat.
      A middle cerebral artery occlusion (MCAO) model was employed in groups of 30-min
      and 2-h focal neocortical ischemia with reperfusion. Neuroproteomes were assessed
      via tandem cation-anion exchange chromatography-gel electrophoresis, followed by
      reversed-phase liquid chromatography-tandem mass spectrometry. MCAO results were
      compared with those from a previous study of focal contusional brain injury
      employing the same methodology to characterize homologous neocortical tissues at
      2 days post-injury. The 30-min MCAO neuroproteome depicted abridged energy
      production involving pentose phosphate, modulated synaptic function and
      plasticity, and increased chaperone activity and cell survival factors. The 2-h
      MCAO data indicated near complete loss of ATP production, synaptic dysfunction
      with degraded cytoarchitecture, more conservative chaperone activity, and
      additional cell survival factors than those seen in the 30-min MCAO model. The
      TBI group exhibited disrupted metabolism, but with retained malate shuttle
      functionality. Synaptic dysfunction and cytoarchitectural degradation resembled
      the 2-h MCAO group; however, chaperone and cell survival factors were more
      depressed following TBI. These results underscore the utility of neuroproteomics
      for characterizing interactive biochemistry for profiling and contrasting the
      molecular aspects underlying the pathobiological differences between types of
      brain injuries.

PMID- 20698762
TI  - Differential protein expression profiling in BSE disease.
AB  - Bovine spongiform encephalopathy (BSE) is a fatal neurodegenerative disease
      affecting cattle. Current tests for the detection of BSE are based solely on the
      only definitive marker of the disease, an abnormal conformer (PrP(d)), of the
      host encoded prion protein (PrP(c)). Recent evidence that other transmissible
      spongiform encephalopathy diseases can be present in the absence of PrP(d),
      coupled with the need to establish pre-mortem diagnostic assays have led to a
      search for alternative diagnostic approaches. In this study we apply differential
      protein expression profiling for the prediction of BSE disease in post-mortem
      bovine brain tissue. The protein profiles of groups of 27 BSE diseased cattle
      were compared with 28 control animals. Analysis using statistical learning (and
      linear discriminant analysis) techniques established protein markers of disease
      with good predictive power (sensitivity 85% and specificity 71%). Further work
      will be required to test the predictive markers in a wider range of diseases,
      particularly other neurological conditions.

PMID- 20698763
TI  - The intersection of culture, disability and assistive technology.
AB  - PURPOSE: Although the use of assistive technology (AT) is by an individual, it
      occurs within a much larger socio-cultural environment. The purpose of this
      article is to describe and analyse current knowledge about the intersection of
      culture and disability in the context of the AT user. METHODS: Literature review
      of theoretical and empirical study papers that discuss cultural aspects related
      to AT use or provision. RESULTS: Understanding how an individual's culturally
      defined identity is shaped as an AT user, and the meaning the AT holds to that
      person and family, is essential to providing culturally appropriate AT services.
      AT providers also belong to a culture framed by their professional experiences;
      needed are ways of addressing ethnocentricity within culturally diverse practice
      settings. Some AT users may identify with a disability culture, a culture formed
      by a shared set of beliefs, values and behaviours around the construct of
      disability. CONCLUSION: This review reveals there is a paucity of knowledge about
      the intersection of AT and culture, and that this intersection requires further
      research. Embarking on this investigation is mandatory if we seek to meet the
      needs of the culturally diverse individuals who use AT.

PMID- 20698764
TI  - Adipose tissue-derived stem cells from humans and mice differ in proliferative
      capacity and genome stability in long-term cultures.
AB  - Adipose tissue-derived stem cells (ASCs) are among the more attractive adult stem
      cell options for potential therapeutic applications. Here, we studied and
      compared the basic biological characteristics of ASCs isolated from humans
      (hASCs) and mice (mASCs) and maintained in identical culture conditions, which
      must be examined prior to considering further potential clinical applications.
      hASCs and mASCs were compared for immunophenotype, differentiation potential,
      cell growth characteristics, senescence, nuclear morphology, and DNA content.
      Although both strains of ASCs displayed a similar immunophenotype, the percentage
      of CD73(+) cells was markedly lower and CD31(+) was higher in mASC than in hASC
      cultures. The mean population doubling time was 98.08 +/- 6.15 h for hASCs and
      52.58 +/- 3.74 h for mASCs. The frequency of nuclear aberrations was noticeably
      lower in hASCs than in mASCs regardless of the passage number. Moreover, as the
      cells went through several in vitro passages, mASCs showed changes in DNA content
      and cell cycle kinetics (frequency of hypodiploid, G0/G1, G2/M, and hyperdiploid
      cells), whereas all of these parameters remained constant in hASCs. Collectively,
      these results suggest that mASCs display higher proliferative capacity and are
      more unstable than hASCs in long-term cultures. These results underscore the need
      to consider specificities among model systems that may influence outcomes when
      designing potential human applications.

PMID- 20698765
TI  - Xenooplasmic transfer between buffalo and bovine enables development of
      homoplasmic offspring.
AB  - Nuclear-mitochondrial incompatibilities may be responsible for the development
      failure reported in embryos and fetuses produced by interspecies somatic cell
      nuclear transfer (iSCNT). Herein we performed xenooplasmic transfer (XOT) by
      introducing 10 to 15% of buffalo ooplasm into bovine zygotes to assess its effect
      on the persistence of buffalo mitochondrial DNA (mtDNA). Blastocyst rates were
      not compromised by XOT in comparison to both in vitro fertilized embryos and
      embryos produced by transfer of bovine ooplasm into bovine zygotes. Moreover,
      offspring were born after transfer of XOT embryos to recipient cows. Buffalo
      mtDNA introduced in zygotes was still present at the blastocyst stage (8.3 vs.
      9.3%, p = 0.11), indicating unaltered heteroplasmy during early development.
      Nonetheless, no vestige of buffalo mtDNA was found in offspring, indicating a
      drift to homoplasmy during later stages of development. In conclusion, we show
      that the buffalo mtDNA introduced by XOT into a bovine zygote do not compromise
      embryo development. On the other hand, buffalo mtDNA was not inherited by
      offspring indicating a possible failure in the process of interspecies mtDNA
      replication.

PMID- 20698766
TI  - Generation of human-induced pluripotent stem cells from gut mesentery-derived
      cells by ectopic expression of OCT4/SOX2/NANOG.
AB  - Induced pluripotent stem (iPS) cells have been generated from human somatic cells
      by ectopic expression of defined transcription factors. Application of this
      approach in human cells may have enormous potential to generate patient-specific
      pluripotent stem cells. However, traditional methods of reprogramming in human
      somatic cells involve the use of oncogenes c-MYC and KLF4, which are not
      applicable to clinical translation. In the present study, we investigated whether
      human fetal gut mesentery-derived cells (hGMDCs) could be successfully
      reprogrammed into induced pluripotent stem (iPS) cells by OCT4, SOX2, and NANOG
      alone. We used lentiviruses to express OCT4, SOX2, NANOG, in hGMDCs, then
      generated iPS cells that were identified by morphology, presence of pluripotency
      markers, global gene expression profile, DNA methylation status, capacity to form
      embryoid bodies (EBs), and terotoma formation. iPS cells resulting from hGMDCs
      were similar to human embryonic stem (ES) cells in morphology, proliferation,
      surface markers, gene expression, and epigenetic status of pluripotent cell
      specific genes. Furthermore, these cells were able to differentiate into cell
      types of all three germ layers both in vitro and in vivo, as shown by EB and
      teratoma formation assays. DNA fingerprinting showed that the human iPS cells
      were derived from the donor cells, and are not a result of contamination. Our
      results provide proof that hGMDCs can be reprogrammed into pluripotent cells by
      ectopic expression of three factors (OCT4, SOX2, and NANOG) without the use of
      oncogenes c-MYC and KLF4.

PMID- 20698767
TI  - Induction of mesenchymal progenitor cells with chondrogenic property from mouse
      induced pluripotent stem cells.
AB  - Despite recent cell-engineering advances, treatment and repair of cartilage
      remains challenging. Although stem cell transplantation therapy using mesenchymal
      stem cells (MSCs) is considered a prominent strategy, the major problem of
      limited proliferative capacity of autologous cells has been unsolved. Recently,
      an induced pluripotent stem (iPS) cell line was suggested as an alternative way
      to cure various human diseases due to their potential proliferating infinitely
      while possessing the capacity to form all types of cells. However, the method to
      induce lineage-restricted differentiation has not been well examined or
      established. Here, we suggest a simple method to induce mesenchymal progenitors
      possessing chondrogenic property from mouse iPS cells. The MSC-like cells
      produced in our study expressed some MSC markers, and could also differentiate to
      osteoblast and adipocyte. The present study demonstrates the property of iPS
      cells as an alternative candidate for treatment of articular disorders, and
      suggests an effective approach for preparing chondrocyte from iPS cells.

PMID- 20698768
TI  - mTOR-mediated activation of p70 S6K induces differentiation of pluripotent human
      embryonic stem cells.
AB  - Deciding to exit pluripotency and undergo differentiation is of singular
      importance for pluripotent cells, including embryonic stem cells (ESCs). The
      molecular mechanisms for these decisions to differentiate, as well as reversing
      those decisions during induced pluripotency (iPS), have focused largely on
      transcriptomic controls. Here, we explore the role of translational control for
      the maintenance of pluripotency and the decisions to differentiate. Global
      protein translation is significantly reduced in hESCs compared to their
      differentiated progeny. Furthermore, p70 S6K activation is restricted in hESCs
      compared to differentiated fibroblast-like cells. Disruption of p70 S6K-mediated
      translation by rapamycin or siRNA knockdown in undifferentiated hESCs does not
      alter cell viability or expression of the pluripotency markers Oct4 and Nanog.
      However, expression of constitutively active p70 S6K, but not wild-type p70 S6K,
      induces differentiation. Additionally, hESCs exhibit high levels of the
      mTORC1/p70 S6K inhibitory complex TSC1/TSC2 and preferentially express more
      rapamycin insensitive mTORC2 compared to differentiated cells. siRNA-mediated
      knockdown of both TSC2 and Rictor elevates p70 S6K activation and induces
      differentiation of hESCs. These results suggest that hESCs tightly regulate
      mTORC1/p70 S6K-mediated protein translation to maintain a pluripotent state as
      well as implicate a novel role for protein synthesis as a driving force behind
      hESC differentiation.

PMID- 20698769
TI  - Optimization of genetic engineering and homologous recombination of collagen type
      I genes in rat bone marrow mesenchymal stem cells (MSC).
AB  - Mutations in COL1A1 or COL1A2 genes lead to osteogenesis Imperfecta (OI) in
      humans. There are three possiblities to successfully treat OI including (1) gene
      therapy, (2) mesenchymal stem cell (MSC) therapy, or (3) a combination of both.
      The aim of this study was to develop a model for combined gene/cell OI therapy by
      targeting Col1a1 and Col1a2 genes with isogenic sequences from corresponding
      human genes in rat bone marrow (BM)-derived MSCs. The recombination efficacy was
      tested for five different rat-human-rat hybrid DNAs with rat fragments that were
      1 to 4 kb long. For selection of transfected clones a neomycine resistance gene
      was cotransfected, and clones resistant to G418 (G418(+)) were recovered and
      screened for integration of specific gene loci in the rat genome. Over 90% of
      G418(+) clones correctly integrated the rat-human-rat hybrid DNAs, and both OI
      loci in the rat genome were targeted to a similar degree. Longer homologous
      sequences integrated into rat collagen genes approximately 10 times more
      efficiently. Based on our data the nonviral gene targeting technology could be
      potentially employed to repair collagen genes in OI patients.

PMID- 20698770
TI  - Acclimatized induction reveals the multipotency of adult human undifferentiated
      keratinocytes.
AB  - It has been demonstrated that several types of somatic stem cells have the
      remarkable capacity to differentiate into other types of tissues. However, the
      promise of keratinocyte stem cells seems slim for generating nonepidermal
      tissues. Using our recently developed acclimatization induction strategy, we
      demonstrate the multipotency of adult human undifferentiated keratinocytes (UKs).
      The UKs were isolated from the basal layer of adult human foreskin and cultured
      in Epilife medium, which allows for the growth of only keratin-positive
      keratinocytes, promotes high proliferation of UKs, and prevents their
      differentiation. Induction of the UKs by either serum or lineage-committed medium
      only produce differentiated epidermal cells. Hence, serum or lineage-committed
      medium was added to Epilife to acclimate UKs to differentiate to other cell
      types. Unexpectedly, serum acclimatization can induce UKs to produce a large
      number of smooth muscle cells and fewer of adipocytes and neurocytes within 3
      weeks. In contrast, except for the terminally differentiated epidermal cells,
      committed acclimatization can induce UKs to differentiate exclusively into the
      adipocytic, myogenic, or neurogenic lineages. These data indicate that human UKs
      represent a novel multipotent adult stem cell, and suggest that they may provide
      an accessible, therapeutically promising cell source for regenerative medicine.

PMID- 20698771
TI  - Human fetal trophonema matrix and uterine endometrium support better human
      embryonic stem cell growth and neural differentiation than mouse embryonic
      fibroblasts.
AB  - The concerns over xenogeneic pathogens and immunogenic molecules derived from
      mouse embryonic fibroblasts (MEFs) trigger the development of human-derived
      feeder layers for human embryonic stem cell (hESC) maintenance. It is essential
      to evaluate the capability of these human feeder layers to retain the stemness
      and pluripotency of hESCs. In the present study, two Chinese hESC lines, SDU
      hESCm-1 and SDU-hESCm-2, were continuously cultured on human adult uterine
      endometrial cells (hUEC), human fetal trophonema matrix cells (hFTMC), and MEFs
      for at least two month (up to 10 passages). A side-by-side comparison of the
      abilities to support: (1) self-renewal of the hESCs, (2) expression of
      undifferentiated markers, and (3) neural differentiation, was made between the
      human and mouse feeder layers. We demonstrated that the hESCs maintained on hUEC
      and hFTMC exhibited significantly higher growth rates and generated higher levels
      of DNA content than those on MEFs. Under neural differentiation-promoting
      conditions, greater neural differentiation was found in the hESCs maintained on
      human than on mouse feeder layers. These results suggest that human feeder layers
      derived from hUECs and hFTMCs are more efficient in supporting a long-term growth
      and neural differentiation of hESCs than MEFs.

PMID- 20698772
TI  - Optimization of culture conditions to support undifferentiated growth of human
      embryonic stem cells.
AB  - Human embryonic stem cells (hESCs) are usually maintained in an undifferentiated
      state by coculture with mitomycin C-treated mouse embryonic fibroblasts (MEFs) as
      feeder cells in the presence of animal sera such as fetal bovine serum (FBS).
      Here, we use primary human amnion epithelial cells (hAECs) as feeder cells and
      human umbilical cord blood serum (CBS) as a replacement for FBS to support
      undifferentiated growth of hESCs. The 5 approximately 10-fold higher expression
      levels of ES cell markers including FGF, Oct-4, Nanog, Sox-2, Rex, and TERT were
      found in hESCs grown on hAECs compared with that on MEFs as measured by
      quantitative real-time polymerase chain reaction (PCR). By immunofluorescence,
      the expresisons of Oct-4 and Nanog is also higher in cells grown on hAECs than
      those on MEFs. Importantly, the ES cells grown on hAECs exhibit normal karyotypes
      on passage 25, thus ruling out the possibility of transformation. Using flow
      cytometry analysis, we show that both the ES cells grown on hAECs and MEFs have
      the same cell cycle distribution pattern. Further, hESCs cultured on hAECs for at
      least 20 passages could differentiate into three germ layers via teratoma
      formation. In addition, chromatin immunoprecipitation assay revealed that histone
      H3 is highly acetylated, and H3 lysine (K) 4 is hypermethylated at the Nanog
      locus and the Oct-4 locus in hESCs grown on hAECs. Conversely, hESCs grown on
      MEFs show histone deacetylation and H3-K4 demethylation. Taken together, these
      results suggest that hAECs supplemented with 10% CBS are suitable for hESC
      culture, and that this method may prove to be valuable for use in future
      regenerative therapies.

PMID- 20698773
TI  - The efficacy of human placenta as a source of the universal feeder in human and
      mouse pluripotent stem cell culture.
AB  - The use of a mouse embryonic fibroblast (MEF) feeder for culture of embryonic
      stem cells (ESCs) is a widely accepted method, regardless of the ESCs' origin and
      type. In this study, we performed the undifferentiated propagation of human ES
      cell lines (hESCs, H1, and HSF6) and mouse ES cell lines (mESCs, D3, and CE3),
      which were previously maintained on an MEF feeder, using human placenta-derived
      fibroblast-like cell (HPC) feeders originated from chorionic villi of women who
      had undergone therapeutic abortion due to known maternal disease that is
      aggravated by pregnancy. Moreover, we tried to introduce the HPC feeder for the
      establishment of inducible pluripotent stem cells (iPSCs) from human placental
      mesenchymal stem cells (MSCs). On the HPC feeder we were able to propagate ESCs
      and iPSCs colonies as an undifferentiated state up to the 50th passage and 20th
      passage, respectively. Maintenance of undifferentiated ESCs was identified by the
      expression of ALP, SSEA-1, SSEA-4, TRA-81, TRA-60, Oct-4, Nanog, or Rex-1. Also,
      addition of leukemia inhibitory factor was not required for undifferentiated
      propagation of mESCs on the HPC feeder. The efficiency and expression of three
      germ layer markers of embryoid bodies (EBs) from ESCs were satisfactory in both
      the MEF and HPC group. EBs formed from iPSCs were scant, and differentiation to
      the three germ layers was identifiable by reverst transcription-polymerase chain
      reactio (RT-PCR) only in the HPC group. In conclusion, the HPC feeder can
      efficiently support the undifferentiated propagation of hESCs, mESCs, and iPSCs,
      suggesting that human placenta may be a useful source of universal feeder cells
      for hESC, mESC, and iPSC culture.

PMID- 20698774
TI  - Generation of mtDNA homoplasmic cloned lambs.
AB  - Generally in mammals, individual animals contain only maternally inherited
      mitochondrial DNA (mtDNA), as paternal (sperm)-derived mitochondria are usually
      eliminated during early development. Somatic cell nuclear transfer (SCNT)
      bypasses the normal routes of mtDNA inheritance and introduces not only a
      different nuclear genome into the recipient cytoplast (in general an enucleated
      oocyte) but also somatic mitochondria. Differences in mtDNA genotype between
      recipient oocytes and potential mtDNA heteroplasmy due to persistence and
      replication of somatic mtDNA means that offspring generated by SCNT are not true
      clones. However, more importantly, the consequences of the presence of somatic
      mtDNA, mtDNA heteroplasmy, or possible incompatibility between nuclear and mtDNA
      genotypes on subsequent development and function of the embryo, fetus and
      offspring are unknown. Following sexual reproduction, mitochondrial function
      requires the biparental control of maternally inherited mtDNA, whereas following
      SCNT incompatibility between the recipient cell mitochondrial and transplanted
      nuclear genomes, or mtDNA heteroplasmy, may result in energy imbalance and
      initiate the onset of mtDNA-type disease, or disruption of normal developmental
      events. To remove the potentially adverse effects of somatic mtDNA following SCNT
      we have previously produced embryos using donor cells depleted to residual levels
      of mtDNA (mtDNA). We now report that these cells support development to term and
      produced live lambs in which no donor somatic mtDNA was detected, the lambs being
      homoplasmic for recipient oocyte DNA.

PMID- 20698775
TI  - Comparative potential of cultured skin fibroblast, cumulus, and granulosa cell to
      produce somatic cell nuclear transfer (SCNT) preimplantation embryos in buffaloes
      (Bubalus bubalis) in relation to gene expressions.
AB  - To improve the efficiency of somatic cell nuclear transfer (SCNT)-derived embryos
      in buffaloes (Bubalus bubalis), skin fibroblast, cumulus, and granulosa cells
      were cultured up to the 15th passage and cloned embryos were produced from each
      cell type. At the 15th passage the cumulative population doublings (CPDs) in
      cumulus cells was higher (60.78) than skin fibroblast (57.12) and granulosa
      (56.05) cell lines. Gene expression of chromatin remodelling proteins, that is,
      HDAC1, DNMT1, DNMT3a, and DNMT3b, were comparable at all five passages (P-3, P-6,
      P-9, P-12, and P-15) groups in cumulus cells but different in skin fibroblast and
      granulosa cells. Cleavage and blastocyst production rate in cumulus (65.9 and
      27.4%)-derived embryos was higher than skin fibroblast (63.8 and 24.3%) and
      granulosa (62.5 and 22.3%)-derived embryos. Expressions of HDAC1, DNMT1, and
      DNMT3a mRNA in cumulus-derived blastocysts were similar to IVF blastocysts
      (control), whereas skin fibroblast and granulosa-derived blastocysts expression
      was significantly different (p < or = 0.05). DNMT3b mRNA expression in all the
      three donor cell types and IVF control were similar. The expression pattern of
      these genes showed the effect of donor cell type with different epigenetic
      reprogramming capabilities for SCNT embryo production rate. Overall, results
      indicated that cumulus cells are the best nuclear donor for SCNT.

PMID- 20698776
TI  - Leukemia inhibitory factor (LIF) enhances germ cell differentiation from primate
      embryonic stem cells.
AB  - Recently, several research groups have shown that germ cells can be produced in
      vitro from pluripotent embryonic stem cells (ESCs). In the mouse, live births of
      offspring using germ cells induced from ESCs in vitro have been reported.
      Furthermore, some efficient methods for inducing the useful number of germ cells
      from ESCs have also been developed. On the other hand, in primates, despite the
      appearances of germ cell-like cells including meiotic cells were observed by
      spontaneous differentiation or introducing transgenes, it has not been determined
      whether fully functional germ cells can be derived from ESCs. To elucidate the
      property for the germ cells induced from primate ESCs, specification of the
      promoting factors for the germ cell development and improving the efficiency of
      germ cell derivation are essential. Leukemia inhibitory factor (LIF) has been
      reported as one of the important factors for mouse primordial germ cell (PGC)
      survival in vitro. However, the effects of LIF on germ cell formation from
      pluripotent cells of primates have not been examined. The aim of this study is to
      determine whether LIF addition can improve in vitro germ cell production from
      cynomolgus monkey ESCs (cyESCs). After 8 days of differentiation, LIF added
      culture induced dome-shaped germ cell colonies as indicated by the intense
      expression of alkaline phosphatase activity (ALP). These cells also demonstrate
      high-level expression of the germ cell-marker VASA, OCT-4, and BLIMP-1, and show
      SSEA-1 expression that supports their early stage germ cell identity. Finally, we
      observed that adding LIF to differentiating cultures inhibited meiotic gene
      expressions and increased the percentage of ALP-positive cells, and demonstrate
      that the addition of LIF to differentiation media increases differentiation of
      early germ cells from the cyESCs.

PMID- 20698778
TI  - Characterization of adherent umbilical cord blood stromal cells regarding
      passage, cell number, and nano-biomarking utilization.
AB  - Adherent umbilical cord blood stromal cells (AUCBSCs) are multipotent cells with
      differentiation capacities. Therefore, these cells have been investigated for
      their potential in cell-based therapies. Quantum Dots (QDs) are an alternative to
      organic dyes and fluorescent proteins because of their long-term photostability.
      In this study we determined the effects of the cell passage on AUCBSCs
      morphology, phenotype, and differentiation potential. QDs labeled AUCBSCs in the
      fourth cell passage were differentiated in the three mesodermal lineages and were
      evaluated using cytochemical methods and transmission electron microscopy (TEM).
      Gene and protein expression of the AUCBSCs immunophenotypic markers were also
      evaluated in the labeled cells by real-time quantitative PCR and flow cytometry.
      In this study we were able to define the best cellular passage to work with
      AUCBSCs and we also demonstrated that the use of fluorescent QDs can be an
      efficient nano-biotechnological tool in differentiation studies because labeled
      cells do not have their characteristics compromised.

PMID- 20698777
TI  - Expansion and characterization of human embryonic stem cell-derived osteoblast
      like cells.
AB  - Human embryonic stem cells (hESCs) have the potential to serve as a repository of
      cells for the replacement of damaged or diseased tissues and organs. However, to
      use hESCs in clinically relevant scenarios, a large number of cells are likely to
      be required. The aim of this study was to demonstrate an alternative cell culture
      method to increase the quantity of osteoblast-like cells directly derived from
      hESCs (hESCs-OS). Undifferentiated hESCs were directly cultivated and serially
      passaged in osteogenic medium (hESC-OS), and exhibited similar expression
      patterns of osteoblast-related genes to osteoblast-like cells derived from
      mesenchymal stem cells derived from hESCs (hESCs-MSCs-OS) and human bone marrow
      stromal cells (hBMSCs-OS). In comparison to hESCs-MSCs-OS, the hESCs-OS required
      a shorter expansion time to generate a homogenous population of osteoblast-like
      cells that did not contain contaminating undifferentiated hESCs. Identification
      of human specific nuclear antigen (HuNu) in the newly formed bone in calvarial
      defects verified the role of the transplanted hESCs-OS as active bone forming
      cells in vivo. Taken together, this study suggests that osteoblast-like cells
      directly derived from hESCs have the potential to serve as an alternative source
      of osteoprogenitors for bone tissue engineering strategies.

PMID- 20698779
TI  - CXCR4+ progenitors derived from bone mesenchymal stem cells differentiate into
      endothelial cells capable of vascular repair after arterial injury.
AB  - Recent findings indicate that bone marrow mesenchymal stem cells (BMSCs)
      participate in the process of neovascularization in response to repair to injury
      and are involved in postinfarction myocardial repair. It is unclear what special
      characteristics the vascular progenitors of bone marrow origin has. CXCR4(+)
      stem/progenitor cells mobilized to the infarct area and improved the myocardial
      repair. In present study, we aimed to determine whether CXCR4(+)BMSCs contribute
      to the angiogenic capacity in vitro and in vivo. CXCR4(+)BMSCs were separated by
      using paramagnetic microbeads and cultured. RT-PCR and FACS analysis confirmed
      the gene expression phenotype. The uptake of acetylated low density lipoprotein
      (acLDL) and the tube formation evaluated the function of CXCR4(+)BMSCs. The
      effect of CXCR4(+)BMSCs transplantation on neovascularization was investigated in
      a murine model hindlimb ischemia. After induced by VEGF, CXCR4(+)BMSCs expressed
      the endothelial cells (ECs) phenotype. The expression of EC markers, PECAM-1, and
      von Willebrand factor (vWF) increased significantly at both the mRNA and protein
      levels. In addition, CXCR4(+)BMSCs enhanced the uptakes of Dil-acLDL and form
      capillary-like tubes in vitro. In vivo the local transfer of CXCR4(+)BMSCs
      increased neovascularization in ischemic hindlimb. These results demonstrate that
      CXCR4(+)BMSCs differentiate into ECs and contribute to neovascularization in the
      vascular lesion,, which indicate the important therapeutic implications for
      cardiovascular diseases and a new cell source for cell-based vascular engineering
      and repair in the future.

PMID- 20698780
TI  - Generation and characterization of neurospheres from canine adipose tissue
      derived stromal cells.
AB  - Adipose tissue-derived stromal cells (ADSCs) have been identified as a powerful
      stem cell source for cellular transplantation therapy. The dog is increasingly
      used as a model of human neurological disease; however, few studies have reported
      induction of canine ADSCs to neural lineages. We characterized canine ADSCs and
      investigated whether they could be induced to differentiate into neural lineages.
      Subcutaneous adipose tissue collected from the dorsal epaxial region of adult
      dogs aged from 1 to 6 years was cultured to produce ADSCs that were then induced
      to neural lineages. RT-PCR, flow cytometry, and immunocytochemistry were
      performed to characterize these cell populations. Morphologically fibroblast-like
      ADSCs were isolated and had similar characteristics to mesenchymal stem cells.
      Under neurogenic conditions containing basic fibroblast growth factor and
      epidermal growth factor, ADSCs formed spherical cellular aggregates that
      resembled neurospheres. RT-PCR confirmed expression of Sox2 and CD90 by these
      aggregates. Expression of neural stem/progenitor markers (Nestin, Sox2, Vimentin)
      and neural lineage markers (A2B5, GFAP, Tuj1) was shown on immunocytochemistry.
      After differentiation, 60% of the cells were Tuj1 positive. In conclusion, we
      isolated and generated neural progenitor cells from canine ADSCs. ADSCs have
      potential for future autologous cell transplantation therapy for neurological
      disorders.

PMID- 20698781
TI  - Enucleated GV oocytes as recipients of embryonic nuclei in the G1, S, or G2
      stages of the cell cycle.
AB  - Universal recipients in the G2 phase of mitotic cell cycle (preactivated oocytes,
      zygotes, blastomeres) accept embryonic nuclei in all the stages of their cell
      cycle. To test if recipients in the G2 of meiotic cycle (immature oocytes) are
      universal recipients, mouse germinal vesicle (GV) oocytes were enucleated and
      reconstructed with blastomere nuclei in the G1, S, or G2 stages. Analysis of
      their maturation has shown that about 30% of the G1 nuclei and 60% of G2 nuclei
      allow for normal metaphase II (MII), both in the oocytes with and without the
      first polar body (1st PB). Among oocytes reconstructed with the S phase nuclei,
      only 8% or less have normal MII, although 75% of them extrude 1st PB. No phase of
      donor cell cycle prevented the abnormal acceleration of 1st PB extrusion, found
      in reconstructed GV oocytes. In conclusion, enucleated GV oocytes are not
      universal recipients of embryonic nuclei, because they do not accept the S
      donors. However, both the G1 and G2 donor nuclei can be reprogrammed in the GV
      oocyte cytoplasm.

PMID- 20698782
TI  - Comparison between the effects of valproic acid and trichostatin A on the in
      vitro development, blastocyst quality, and full-term development of mouse somatic
      cell nuclear transfer embryos.
AB  - Reprogramming of differentiated nuclei into a totipotent embryonic state
      following somatic cell nuclear transfer (SCNT) is not efficient. Previous studies
      in the hybrid B6D2F1 mouse strain revealed that a transient treatment of the SCNT
      embryos with the histone deacetylase inhibitor (HDACi) trichostatin A (TSA)
      significantly enhance the potential of the cloned embryos to develop in vitro and
      to term. Here, we compare two different SCNT protocols with TSA and explore, for
      the first time, the effect of another HDACi, valproic acid (VPA), on the in vitro
      development, blastocyst quality, and full-term development of mouse B6CBAF1
      cloned embryos. Rates of blastocyst development in SCNT embryos treated with
      either 5 nM TSA during and after activation (31.8%) or with 100 nM TSA or 2 mM
      VPA before and during activation (34.5 and 38.3%, respectively) were clearly
      superior to those of nontreated SCNT embryos (22.9-25.1%). These increased in
      vitro development rates of the HDACi-treated embryos were correlated with an
      increased level of histone H3 lysine 14 acetylation and an improved blastocyst
      quality, as judged by the increased number of total and ICM cells in comparison
      to the nontreated embryos (30-35% increase). Treatment of SCNT embryos with TSA
      or VPA also allowed the obtention of viable cloned mice, whereas none could be
      produced from untreated SCNT embryos. In conclusion, we have demonstrated for the
      first time that VPA can improve the in vitro and full-term development of B6CBAF1
      SCNT embryos, at a similar level as TSA. Our findings may open new opportunities
      to improve cloning efficiencies in other mouse strains or species.

PMID- 20698783
TI  - Directed differentiation into neural lineages and therapeutic potential of
      porcine embryonic stem cells in rat Parkinson's disease model.
AB  - This study was conducted to direct porcine embryonic stem (pES) cells
      differentiating into neural lineages and to investigate therapeutic potential of
      GFP-expressing pES (pES/GFP(+)) in the rat model of Parkinson's disease (PD).
      Directed differentiation of pES into neural lineages was induced by suspension
      culture in medium containing RA, SHH, and FGF combinations without going through
      embryoid body formation. A high yield of nestin-expressing neural precursors was
      found in all treatments on day 2 after the 12-day induction. On day 6 after
      replating, more than 86.2 and 83.4% of the differentiated cells stained
      positively for NFL and MAP2, respectively. The expression of TH, ChAT, and GABA
      specific markers were also observed in these NFL-positive neural cells. The
      undifferentiated pES/GFP(+) cells and their neuronal differentiation derivatives
      were transplanted into the Sprague-Dawley (SD) rat's brain, and their survival
      and development was determined by using live animal fluorescence optical imaging
      system every 15 days. The results showed that fluorescent signals from the
      injection site of SD rats' brain could be detected through the experimental
      period of 3 months. The level of fluorescent signal detected in the treatment
      group was twofold that of the control group. The results of behavior analysis
      showed that PD rats exhibited stably decreased asymmetric rotations after
      transplantation with pES/GFP(+)-derived D18 neuronal progenitors. The
      dopaminergic differentiation of grafted cells in the brain was further confirmed
      by immunohistochemical staining with anti-TH, anti-DA, and anti-DAT antibodies.
      These results suggested that the differentiation approach we developed would
      direct pES cells to differentiate into neural lineages and benefit the
      development of novel therapeutics involving stem cell transplantation.

PMID- 20698784
TI  - Anomalous oxygen consumption in porcine somatic cell nuclear transfer embryos.
AB  - Oxygen consumption reflects overall metabolic activity of mammalian embryos. We
      measured oxygen consumption in individual porcine somatic cell nuclear transfer
      (SCNT) and in vitro-fertilized (IVF) embryos by modified scanning electrochemical
      microscopy. Oxygen consumption in IVF embryos rapidly increased at day 5 of the
      blastocyst stage (D5BL). IVF embryos that consumed >0.81 x 10(14)/mol sec(-1) of
      oxygen at D5BL exhibited significantly higher hatching and hatched rates at D7BL,
      whereas D5BL SCNT embryos using porcine fetal fibroblasts did not show an
      increase in oxygen consumption until D7BL. The numbers of inner cell mass and
      trophectoderm (TE) cells and incidence of apoptosis did not significantly differ
      between IVF and SCNT embryos at D5BL. At D7BL, a significant lower number of TE
      cell and higher incidence of apoptosis were observed in SCNT than in IVF embryos;
      this significantly correlated with their oxygen consumption at D5BL. Use of
      cumulus cells as donor cells neutralized the low oxygen consumption in SCNT
      embryos at D5BL, regardless of the difference between the recipient cytoplasm and
      donor nucleus. Some of SCNT embryos at D7BL were retrieved the hatching
      completion and were improved the number of TE cell and apoptosis incidence by
      using cumulus cells. Thus, anomalous oxygen consumption in porcine SCNT embryos
      at D5BL could be sign of limited hatchability, which may be responsible for the
      low TE cell number and high apoptosis incidence.

PMID- 20698785
TI  - High hydrostatic pressure treatment of porcine oocytes induces parthenogenetic
      activation.
AB  - An innovative technique called high hydrostatic pressure (HHP) treatment has
      recently been reported to improve the cryosurvival of gametes and embryos in
      certain mammalian species, including the mouse, pig, and cattle. In the present
      study the parthenogenetic activation (PA) of pig oocytes caused by HHP treatment
      was investigated in different holding media with or without Ca(2+). The
      efficiency of activation was tested at different pressure levels and media
      including T2 (HEPES-buffered TCM-199 containing 2% cattle serum), and mannitol
      PVA fusion medium with (MPVA + Ca(2+)) or without Ca(2+) and Mg(2+)(MPVA). The
      results showed that HHP cannot induce PA in T2, but only in MPVA + Ca(2+) with
      low Ca(2+) concentration and MPVA without Ca(2+). The highest activation
      efficiency was achieved with 10 min HHP treatment using 100 or 200 bars for
      oocytes in MPVA + Ca(2+) or MPVA, respectively. In the light of these results,
      the possible source of Ca(2+) during activation was investigated. It was found
      that even after a total of 30-min wash with TL-HEPES-PVA buffer without Ca(2+)
      before HHP treatment in MPVA, the oocytes could still be activated, indicating
      the possibility of an intracellular Ca(2+) source caused cytoplasmic free Ca(2+)
      elevation. In conclusion, parthenogenetic activation could be induced by HHP in
      certain holding media with low or zero Ca(2+) content. Further experiments are
      needed to identify the exact mechanisms of activation.

PMID- 20698786
TI  - In vitro development and chromosomal configuration of bovine somatic cloned
      embryos with nonenucleated metaphase II oocytes.
AB  - This study was designed to examine the effects of the presence of oocyte nuclei
      on the donor cell nuclear remodeling, including premature chromosome condensation
      (PCC) and DNA configuration, and subsequent embryo development. The results
      showed that: (1) the presence of oocyte MII spindles was more likely to induce
      donor cell PCC. (2) The positional relationship between the fused donor cell and
      the oocyte metaphase spindle had an effect on oocyte PB2 extrusion. When the
      fused donor cell was widely separated from the MII spindle, 94.4% of the
      reconstructed oocytes expelled a PB2. When the donor cell was fused adjacently to
      the MII spindle, almost all of the reconstructed oocytes did not expel the PB2;
      the majority (67.9%) formed a very large M-phase spindle in which the oocyte and
      the donor cell chromosomes merged. (3) After activation, the oocyte and donor
      nuclei exhibited a variety of pronuclear patterns and asynchronous development.
      (4) The embryos reconstituted with nonenucleated oocytes resulted in a similar
      cleavage rate as observed in the control embryos reconstituted with enucleated
      oocytes. Blastocyst developmental rates were no different between nonenucleated
      and enucleated cloned embryos; however, the development rates from early to
      hatching blastocysts significantly decreased in the nonenucleation group compared
      to enucleation controls (0 vs. 23.1%; 27.5 vs. 67.8%), regardless with either
      cumulus cells or fibroblasts as donor cells. (5) All nonenucleated oocyte-derived
      blastocysts contained mixed polyploidy with a variety of compositions that
      included 2n/4n, 2n/6n, 2n/8n, and 2n/4n/8n. (6) Nuclear transfer preceding the
      oocyte enucleation experiment indicated that prolonged presence of oocyte nuclei
      induced abnormal DNA configuration and reduced in vitro development of
      transferred somatic nuclei, but short time presence of oocyte nuclei did not
      affect the in vitro development of cloned embryos. We conclude that oocyte MII
      spindles induce donor cell PCC, the developmental capacity of cloned embryos
      reconstituted with nonenucleated oocytes is inferior to those with enucleated
      oocytes, and that all such derived blastocysts are polyploidy.

PMID- 20698787
TI  - Activation with ionomycin followed by dehydroleucodine and cytochalasin B for the
      production of parthenogenetic and cloned bovine embryos.
AB  - In this work, Dehydroleucodine (DhL) was evaluated as a chemical activator of
      bovine oocytes and somatic cell nuclear transfer (SCNT) reconstituted embryos.
      Oocytes were activated with 5 microM Ionomycin (Io) and exposed for 3 h to 1 or 5
      microM DhL alone (Io-Dhl1 or Io-DhL5) or combined with Cytochalasin B (Io
      DhL1/CB; Io-DhL5/CB). Control groups were Io (Io), Io followed by 1.9 mM 6
      Dimethylaminopurine (Io-6DMAP), and embryos produced by in vitro fertilization
      (IVF). Pronuclear formation and development to blastocysts of activated oocytes
      were evaluated. Embryos obtained by the DhL concentration that induced the
      highest blastocyst rates (1 microM) were karyotyped. An additional treatment
      based in Io-DhL1 plus lengthened (6-h) exposure to CB (Io-DhL1/long CB) was
      included to improve the proportion of diploid blastomeres. Finally, DhL combined
      with CB was employed to assist cloning by intracytoplasmic injection of whole
      cumulus cells. Results showed that DhL induces a pronuclear formation dynamic
      that was more similar to IVF-produced embryos than DMAP. Development to
      blastocyst stage was higher after activation with 1 microM DhL than with 5 microM
      DhL, either for groups combined or not with CB (19.15; 21.74 vs. 6.82; 0%,
      respectively) (p < 0.05). Io-DhL1 and Io-DhL1/CB treatments induced blastocyst
      cleaved embryo ratios not statistically different from those of Io-DMAP (35.85%)
      and IVF (33.33%) groups (p > 0.05). Io-DhL1/long CB induced higher diploid
      blastomere rates than Io-Dhl1, Io-DhL1/CB and Io-DMAP (63.8 vs. 36.8; 40 and
      31.6%, respectively) (p < 0.05). Moreover, all DhL treatments resulted in
      polyploidy rates that were lower than Io-DMAP (5.2, 12.0, 10.6, and 31.6%,
      respectively) (p < 0.05). Io-DhL1/CB and Io-DhL1/long CB induced cloned embryo
      blastocyst rates that were not significantly different from Io-DMAP (6.1, 9.4,
      and 18.3%, respectively) (p < 0.05). Our results indicate that Io-DhL1/long CB
      protocol could be useful for SCNT programs.

PMID- 20698788
TI  - Cost of a naturally occurring two-amino acid deletion in cytochrome c oxidase
      subunit 7A in Drosophila simulans.
AB  - This study aimed to determine whether a naturally occurring (DeltaTrp85,
      DeltaVal86) deletion from a protein subunit of cytochrome c oxidase (complex IV)
      influenced cytochrome c oxidase activity, mRNA expression levels of electron
      transport chain genes, and aspects of adult female fitness in the fly Drosophila
      simulans. We modeled the tertiary structure of D. simulans cox7A containing the
      deletion by homology to the bovine cox7A structure and predicted that it would
      decrease the function of complex IV. This prediction led to the hypothesis that
      flies with the deletion would have lower cytochrome c oxidase activity and higher
      levels of mRNA expression from cox7A. This result was observed, but unexpectedly,
      elevated levels of mRNA expression were also observed in genes encoding subunits
      of complexes I, III, and IV. Together these data suggest that the deletion causes
      a high bioenergetic cost to the organism. To investigate the predicted cost at a
      physiological level, we assayed aspects of adult female fitness. Starvation
      sensitivity but not feeding rate was significantly influenced by the two-amino
      acid deletion. Further, we observed that carbohydrate and protein levels but not
      lipid levels were higher in the mutant flies. Together, these data show that
      quaternary structure modeling and biochemistry can be used to link the genotype
      with the organismal phenotype.

PMID- 20698789
TI  - Stroke participants' perceptions of robotic and electrical stimulation therapy: a
      new approach.
AB  - PURPOSE: User perceptions are critical, yet often ignored factors in the design
      and development of rehabilitation technologies. In this article, measures for
      collection of patient perceptions are developed and applied to a novel upper limb
      workstation that combines robotic therapy and electrical stimulation (ES).
      METHOD: Five participants with chronic upper limb hemiplegia post-stroke used a
      robotic workstation to undertake supported tracking tasks augmented by precisely
      controlled ES to their triceps muscle. Following a 6 week trial, a purpose
      designed set of questions was developed and individual interviews were conducted
      by an independent health psychologist. RESULTS: The simple, quick to administer
      question set showed that participants had a positive response to the system, and
      contributed valuable feedback with regard to its usability and effectiveness.
      Participants want a home-based system targeting their whole arm. CONCLUSION: This
      article demonstrates the value in assessing user perceptions of a rehabilitation
      system via a simple question set. While the results of this study have
      implications for a wider audience, our recommendations are for a qualitative
      study to develop a generic evaluation tool which could be used across the growing
      number of devices to provide feedback to enhance future development of any new
      technology for rehabilitation.

PMID- 20698790
TI  - Longitudinal analysis of serological responses of adults to Helicobacter pylori
      antigens.
AB  - Because Helicobacter pylori persist for decades in the human stomach, the aim of
      this study was to examine the long-term course of H. pylori-specific serum
      immunoglobulin G (IgG) responses with respect to subclass and antigenic target.
      We studied paired serum samples obtained in 1973 and in 1994 in Vammala, Finland,
      from 64 healthy H. pylori-positive adults and from other healthy control
      subjects. H. pylori serum immunoglobulin A, IgG, and IgG subclass responses were
      determined by antigen-specific enzyme-linked immunosorbent assays. H. pylori
      specific IgG1 and IgG4 subtype responses from 47 subjects were similar in 1973
      and 1994, but not when compared with unrelated persons. H. pylori-specific
      IgG1:IgG4 ratios among the participants varied >1000-fold; however, 57 (89.1%) of
      64 subjects had an IgG1:IgG4 ratio >1.0, consistent with a predominant IgG1 (Th1)
      response. Furthermore, ratios in individual hosts were stable over the 21-year
      period (r = 0.56; P < .001). The immune response to heat shock protein HspA was
      unchanged in 49 (77%) of the 64 subjects tested; of the 15 whose serostatus
      changed, all seroconverted and were significantly younger than those whose status
      did not change. These findings indicate that H. pylori-specific antibody
      responses are host-specific with IgG1:IgG4 ratios stable over 21 years, IgG1
      responses predominating, and HspA seroconversion with aging.

PMID- 20698791
TI  - Nonhuman primate calorie restriction.
AB  - Calorie restriction (CR) is the only dietary intervention that repeatedly extends
      both median and maximal lifespan in a broad range of species. Although there has
      been considerable interest in CR and its ability to retard aging, the mechanism
      has remained elusive. In contrast to studies in rodent and nonmammalian systems
      that are now beginning to provide mechanistic insights into how CR promotes
      longevity, the efficacy of CR in delaying primate aging has yet to be fully
      demonstrated. Here we review some of the insights from CR studies in short-lived
      species. We describe the advantages of using the rhesus monkey as a model for
      human aging and detail how CR can be successfully implemented in this species. We
      discuss the findings from our ongoing longitudinal study and outline the effects
      to date of CR on rhesus monkey health. Finally, we highlight the importance of
      primate studies in the context of aging research and its potential to advance our
      understanding of human aging and health.

PMID- 20698792
TI  - Coordination of DNA-PK activation and nuclease processing of DNA termini in NHEJ.
AB  - DNA double-strand breaks (DSB), particularly those induced by ionizing radiation
      (IR), are complex lesions that can be cytotoxic if not properly repaired. IR
      induced DSB often have DNA termini modifications, including thymine glycols, ring
      fragmentation, 3'-phosphoglycolates, 5'-hydroxyl groups, and abasic sites.
      Nonhomologous end joining (NHEJ) is a major pathway responsible for the repair of
      these complex breaks. Proteins involved in NHEJ include the Ku 70/80 heterodimer,
      DNA-PKcs, processing proteins including Artemis and DNA polymerases MU and
      lambda, XRCC4, DNA ligase IV, and XLF. We will discuss the role of the physical
      and functional interactions of DNA-PK as a result of activation, with an emphasis
      on DNA structure, chemistry, and sequence. With the diversity of IR induced DSB,
      it is becoming increasingly clear that multiple DNA processing enzymes are likely
      necessary for effective repair of a break. We will explore the roles of several
      important processing enzymes, with a focus on the nuclease Artemis and its role
      in processing diverse DSB. The effect of DNA termini on both DNA-PK and Artemis
      activity will be analyzed from a structural and biochemical view.

PMID- 20698795
TI  - Retraction. Site-specific transgene integration in the human genome catalyzed by
      phiBT1 phage integrase.

PMID- 20698793
TI  - A "Wii" bit of fun: the effects of adding Nintendo Wii((r)) Bowling to a standard
      exercise regimen for residents of long-term care with upper extremity
      dysfunction.
AB  - The aims of this randomized, single-blind crossover trial were to investigate the
      effect of adding a simulated bowling video game via the Nintendo Wii((r)) gaming
      system to the standard exercise regimen of cognitively intact residents of long
      term care (LTC) with upper extremity dysfunction and to identify individual
      characteristics that might predict improvement. Residents (n=34) were recruited
      through two LTC facilities in southwestern Ontario and were randomized into a
      standard exercise (SG) or standard exercise plus Wii bowling (Wii) arm. After 4
      weeks of intervention, the groups were crossed over to the opposite arm. Outcomes
      included measures of pain intensity and bothersomeness, physical activity
      enjoyment, and a six-item measure of functional capacity designed specifically
      for residents of LTC. Results suggest that subjects improved on all outcomes from
      pre- to postintervention but that only enjoyment of activity showed a significant
      difference between the SG and Wii groups. Effect sizes (Cohen's d) ranged from
      small (0.30 for bothersomeness) to large (1.77 for functional capacity).
      Responders, defined as those subjects who reported any degree of improvement
      following the Wii intervention, were less likely to complain of stiffness or
      shoulder symptoms and were more likely to complain of hand symptoms than non
      responders. Limitations in interpretation and recommendations for future research
      are presented.

PMID- 20698796
TI  - Safety of moxifloxacin and voriconazole in corneal storage media on porcine
      corneal endothelial cells.
AB  - PURPOSE: The aim of this study was to evaluate the safety of moxifloxacin and
      voriconazole as a supplement in corneal storage media for porcine corneal
      endothelial cells. METHODS: Twenty-eight eyes were divided into 4 groups. In the
      control group (the C group), corneal buttons were stored for 3 days in Optisol
      GS. In the treatment group, the corneal buttons were preserved for 3 days in
      Optisol-GS mixed with 250 microg/mL moxifloxacin (M group), 100 microg/mL
      voriconazole (V group), and 250 microg/mL moxifloxacin plus 100 microg/mL
      voriconazole (MV group). We evaluated the samples via specular microscopy before
      and after 3 days of preservation. The mean changes of endothelial cell counts
      were compared among the 4 groups. Scanning electron microscopy was conducted
      after 3 days of preservation. RESULTS: Before the preservation, the endothelial
      cell counts did not differ among the 4 groups (P > 0.05). After 3 days of
      preservation, the endothelial cell count in the MV group was the lowest among the
      4 groups (P < 0.05). After 3 days of preservation, the rate of corneal
      endothelial cell loss in the M and V groups did not differ significantly from the
      control group (P > 0.05). The rate of endothelial cell loss in the MV group was
      significantly higher than that of the control group (P < 0.05). Scanning electron
      microscopy revealed a normal mosaic pattern for the C, V, and F groups, but
      hexagonality was not preserved in the MV group. CONCLUSION: Preservation in
      Optisol-GS mixed with moxifloxacin (250 microg/mL) plus voriconazole (100
      microg/mL) induced significant toxicity on the endothelial cells in porcine
      corneas, when compared with the control group.

PMID- 20698797
TI  - The effect of gender and iris color on the dark-adapted pupil diameter.
AB  - PURPOSE: The aims of this study were to assess the utility of digital color
      sensing to quantify iris color using digital photographs and to determine whether
      gender or iris color affects the dark-adapted pupil diameter (DAPD). METHODS:
      Subjects aged 18-80 years (N = 263) with no eye disease had their right DAPD
      measured after 2 min of dark adaptation at 1 lux using the NeurOptics
      pupillometer. A high-resolution digital slit lamp photograph of the iris was
      taken, and iris color was subjectively classified as blue, blue-green, green
      brown, light brown, or dark brown. The digital photographs were objectively
      measured on-screen with the Minolta TV Color Analyzer II using the Commission
      Internationale de l'Eclairage system of color description. Regression analyses
      were performed to identify correlations between subjective iris color, Commission
      Internationale de l'Eclairage measurements, and DAPD. RESULTS: Gender and iris
      color had no effect on the DAPD. The Minolta TV Color Analyzer could discriminate
      all blue eyes (blue and blue-green) from all brown eyes (light and dark) but
      could not distinguish between shades of blue or shades of brown. Green-brown
      irises had no unique chromatic properties and could not be distinguished from
      other colors using our technique of digital color analysis. The Minolta device
      was simple and efficient to use. CONCLUSIONS: Contrary to long-held beliefs,
      female patients and blue-eyed patients do not have larger DAPD. Digital color
      sensing is a useful technique for objectively describing iris color.

PMID- 20698798
TI  - Prevention of myopia onset with 0.025% atropine in premyopic children.
AB  - PURPOSE: To evaluate the efficacy of 0.025% atropine solution for prevention of
      myopic shift and myopia onset in premyopic children. METHODS: This study was
      designed as a retrospective cohort study. Six- to 12-year-old children with
      spherical equivalent refraction of <+1 diopter (D) (defined as premyopia), with
      cylindrical refraction of <-1 D, without amblyopia, and who received 0.025%
      atropine eye drops at bedtime every night or no treatment after follow-up for at
      least 12 months were enrolled. Fast myopic shift is defined as a myopic shift >
      0.5 D per year. RESULTS: Fifty children were enrolled in the study. Twenty-four
      children (average age 7.6 years old) were in the 0.025% atropine group, and 26
      children (average age: 8.2 years old) were in the control group. The mean
      spherical refraction myopic shift in the 0.025% atropine group was -0.14 +/- 0.24
      D/year, significantly lower than that in the control group, -0.58 +/- 0.34 D/year
      (P < 0.0001). In multiple linear regression analysis, 0.025% atropine treatment
      was the only independent variable in preventing myopia shift. There were
      statistically significant differences between the 0.025% atropine group and the
      control group in myopia onset and fast myopic shift (21% vs. 54%, P = 0.016; 8%
      vs. 58%, P = 0.0002, respectively). There was no difference between the 2 groups
      with regard to the symptom of photophobia (16% vs. 8%, P = 0.409). None of the
      children in either group complained of near-blurred vision. CONCLUSIONS: Regular
      topical administration of 0.025% atropine eye drops can prevent myopia onset and
      myopic shift in premyopic schoolchildren for a 1-year period.

PMID- 20698799
TI  - A comparison of cyclosporine 0.05% ophthalmic emulsion versus vehicle in Chinese
      patients with moderate to severe dry eye disease: an eight-week, multicenter,
      randomized, double-blind, parallel-group trial.
AB  - PURPOSE: The goals of this study were to compare the efficacy and safety profile
      of topical cyclosporine 0.05% versus vehicle in Chinese patients with moderate to
      severe dry eye disease. METHODS: In this multicenter, randomized, double-blind,
      vehicle-controlled, parallel-group study, 233 dry eye patients were allocated to
      receive either cyclosporine 0.05% or vehicle twice daily for 8 weeks. Primary
      outcome was the difference between groups, in total score of 4 symptoms and 4
      signs change from baseline at weeks 2, 4, and 8. Changes in symptoms (ocular
      dryness, foreign body sensation, photophobia and burning) and signs (conjunctival
      hyperemia, Schirmer test, tear Break-up time (BUT), and corneal punctate
      fluorescein staining) at weeks 2, 4, and 8 as well as frequency of administration
      of concomitant artificial tears, were considered as secondary outcomes. The
      safety profile was evaluated by examining adverse events, changes in visual
      acuity, and ocular tolerance. RESULTS: Greater improvements of the total score
      were seen in cyclosporine 0.05% group than in the vehicle group at all follow-up
      times (P < 0.01). Improvements in ocular dryness at week 8 (P = 0.040) and
      foreign body sensation during weeks 4 and 8 (P < 0.020) were significantly
      greater with cyclosporine. In addition, compared with the vehicle, cyclosporine
      significantly improved 2 objective dry eye disease signs: corneal staining at
      weeks 4 (P = 0.025) and 8 (P = 0.050) and the Schirmer test at week 4 (P =
      0.035). However, no between-group difference approached statistical significance
      in photophobia, burning, BUT value, conjunctival hyperemia and frequency of
      administration of concomitant artificial tears at any follow-up times (P >
      0.05).The cumulative frequency of adverse events did not significantly differ
      between the groups (P = 0.519), which were 11.21% and 8.55%, respectively. There
      were no patients who experienced reduced visual acuity. CONCLUSION: Cyclosporine
      0.05% ophthalmic emulsion is an effective and safe treatment for Chinese patients
      with moderate to severe dry eye disease.

PMID- 20698800
TI  - Efficacy and tolerability of imiquimod 5% cream to treat periocular basal cell
      carcinomas.
AB  - PURPOSE: To assess the efficacy and safety of nonsurgical treatment with
      imiquimod (IMQ) 5% cream in patients with periocular nodular basal cell carcinoma
      (BCC). METHODS: Fifteen patients with clinical and histopathological diagnosis of
      nodular BCC on the eyelid were treated with IMQ 5% cream once daily, 5 days/week
      for 6 weeks. Three patients had tumor persistence after photodynamic therapy and
      1 patient had failed cryotherapy. RESULTS: All tumors showed histopathological
      remission within 3 months of starting IMQ, and sustained clinical remission was
      documented in each patient after 24-28 months' follow-up. Treatment tolerability
      was bad in 7 patients with local effects being most problematic, but all symptoms
      disappeared when treatment ended. CONCLUSIONS: IMQ therapy is effective for
      treating periocular BCCs with a cure rate similar to that of surgery. Aesthetic
      results were rated as excellent. IMQ is a useful alternative to surgery in
      patients with periocular BCCs when other therapies have failed or are not
      possible.

PMID- 20698801
TI  - Anti-aquaporin-4 antibody-positive optic neuritis treated with double-filtration
      plasmapheresis.
AB  - PURPOSE: The anti-aquaporin-4 (AQP4) antibody was recently reported to be
      associated with neuromyelitis optica (NMO). Optic nerve involvements in many NMO
      cases are bilateral and the prognosis is poor. However, it has been suggested
      that plasma exchange is effective for those patients when steroid pulse therapy
      is ineffective. Herein, we report successful treatment of a patient with NMO
      using double-filtration plasmapheresis (DFPP). CASE: A 22-year-old woman
      consulted a neurologist for neck pain in March 2008. High-intensity lesions were
      shown in the cervical spinal cord by T2-weighted magnetic resonance imaging. On
      July 15, the patient was referred to our department for a headache and pain and
      blurred vision in the left eye. The best-corrected visual acuity was 20/50 and
      20/500 in the right and left eyes, respectively, with visual field defects
      observed in both. After 3 courses of steroid pulse therapy, anti-AQP4 antibodies
      were positive. In November, the patient again noticed visual acuity loss in the
      left eye and was treated by additional steroid pulse therapy, which was not
      effective. Next, she underwent plasma exchange therapy, though it was stopped due
      to hypotension and dyspnea. The next day, the patient underwent DFPP treatment
      and visual function gradually recovered. CONCLUSION: It is important to consider
      NMO when steroid pulse therapy is not effective. We successfully and safely
      treated NMO in a young adult patient using DFPP.

PMID- 20698803
TI  - Relationship of mid-thigh adiposity to the metabolic syndrome in postmenopausal
      women.
AB  - BACKGROUND: In postmenopausal women, a population at risk for the metabolic
      syndrome, the relative contribution of central fat versus peripheral muscle fat
      to the metabolic risk profile is unknown. This study explored the relationship
      between muscle fat infiltration derived from computed tomography (CT) scans and
      metabolic syndrome. METHODS: Mid-thigh CT scans measured the surface of muscle
      with low attenuation (LAMS) [0-34 Hounsfield units (HU)], which represented the
      specific component of fat-rich muscle. Insulin sensitivity was evaluated by an
      euglycemic-hyperinsulinemic clamp. National Cholesterol Education Program Adult
      Treatment Panel III (NCEP ATP III) criteria were used to determine the presence
      of the metabolic syndrome. RESULTS: A total of 103 postmenopausal women were
      studied. Metabolic syndrome was found in 43 women with significantly higher
      levels of abdominal adiposity, higher LAMS (27 +/- 8 vs. 23 +/- 7 cm(2)), and
      lower insulin sensitivity compared to those without the metabolic syndrome. Women
      with higher levels of LAMS presented higher metabolic risk features such as
      higher blood pressure, abdominal adiposity, inflammatory markers, and blood lipid
      levels. LAMS and visceral adipose tissue correlated significantly with the
      presence of metabolic syndrome, but these relationships were lost when LAMS was
      adjusted for visceral adipose tissue but not when visceral adipose tissue was
      adjusted for LAMS. CONCLUSIONS: These results suggest that postmenopausal women
      who present with metabolic syndrome had increased fat-rich mid-thigh muscle.
      Moreover, women with more fat-rich muscle had many features of the metabolic
      syndrome. These relations were weakened when visceral adipose tissue was taken
      into account suggesting that LAMS may play a relatively smaller role, compared to
      VAT, in the contribution to the metabolic syndrome.

PMID- 20698802
TI  - Ability among adolescents for the metabolic syndrome to predict elevations in
      factors associated with type 2 diabetes and cardiovascular disease: data from the
      national health and nutrition examination survey 1999-2006.
AB  - OBJECTIVE: The aim of this study was to compare currently proposed sets of
      pediatric metabolic syndrome criteria for the ability to predict elevations in
      "surrogate" factors that are associated with metabolic syndrome and with future
      cardiovascular disease and type 2 diabetes mellitus. These surrogate factors were
      fasting insulin, hemoglobin A1c (HbA1c), high-sensitivity C-reactive protein
      (hsCRP), and uric acid. METHODS: Waist circumference (WC), blood pressure,
      triglycerides, high-density lipoprotein cholesterol (HDL-C), fasting glucose,
      fasting insulin, HbA1c, hsCRP, and uric acid measurements were obtained from
      2,624 adolescent (12-18 years old) participants of the 1999-2006 National Health
      and Nutrition Examination Surveys. We identified children with metabolic syndrome
      as defined by six commonly used sets of pediatric metabolic syndrome criteria. We
      then defined elevations in the surrogate factors as values in the top 5% for the
      cohort and calculated sensitivity, specificity, positive predictive value (PPV),
      and negative predictive value (NPV) for each set of metabolic syndrome criteria
      and for each surrogate factor. RESULTS: Current pediatric metabolic syndrome
      criteria exhibited variable sensitivity and specificity for surrogate
      predictions. Metabolic syndrome criteria had the highest sensitivity for
      predicting fasting insulin (40-70%), followed by uric acid (31-54%), hsCRP (13
      31%), and HbA1c (7-21%). The criteria of de Ferranti (which includes children
      with WC >75(th) percentile, compared to all other sets including children with WC
      >90(th) percentile) exhibited the highest sensitivity for predicting each of the
      surrogates, with only modest decrease in specificity compared to the other sets
      of criteria. However, the de Ferranti criteria also exhibited the lowest PPV
      values. Conversely, the pediatric International Diabetes Federation criteria
      exhibited the lowest sensitivity and the highest specificity. CONCLUSIONS:
      Pediatric metabolic syndrome criteria exhibit moderate sensitivity for detecting
      elevations in surrogate factors associated with metabolic syndrome and with risk
      for future disease. Inclusion of children with more modestly elevated WC improved
      sensitivity.

PMID- 20698804
TI  - Whole-body MRI with assessment of hepatic and extraabdominal enhancement after
      administration of gadoxetic acid for staging of rectal carcinoma.
AB  - BACKGROUND: In TNM staging of rectal cancer by MRI, unspecific extracellular
      contrast agent Gd-DTPA is established for extrahepatic and vascular enhancement
      whereas liver-specific gadoxetic acid has proven high accurate detection of liver
      metastasis. PURPOSE: To compare intraindividually the qualification and
      quantification of enhancement in liver parenchyma, abdominal, pulmonary, and
      pelvic vessels between gadoxetic acid and Gd-DTPA. MATERIAL AND METHODS: Sixteen
      patients with histologically proven rectal carcinoma (mean age 62.9 years) were
      imaged twice by MRI. For pretherapeutic staging 10 mL gadoxetic acid (mean dose
      0.032 mmol Gd/kg body weight) and for restaging after neoadjuvant therapy Gd-DTPA
      (0.1 mmol Gd/kg body weight) were administered. The liver was acquired in
      arterial-dominant and portal venous phases, the thorax and pelvis were depicted
      in venous phases using three-dimensional T1-weighted sequences. Contrast
      enhancement was rated by two independent readers and compared by means of
      multinomial regression analysis using generalized estimating equations. Signal-to
      noise ratios were compared by two-sided paired t-tests. RESULTS: Overall contrast
      enhancement was rated sufficient for diagnosis in all examinations and both
      contrast agents. Vascular enhancement was rated comparable with exception of the
      aorta, the peripheral intrahepatic veins, and the central lung vessels (p =
      0.0182, p = 0.0053, p = 0.0083, in favor of Gd-DTPA). Quantitative evaluation
      revealed no statistically significant differences in parenchymal and vascular
      signal-to-noise ratios with exception of the aorta, and the central pulmonary
      artery (67.4 vs. 89.3; p = 0.0421, 44.5 vs. 59.5; p = 0.0446 respectively, in
      favor of Gd-DTPA). CONCLUSION: The contrast enhancement after gadoxetic acid is
      comparable to Gd-DTPA and appears suitable for comprehensive TNM-staging by
      combining high accurate liver-specific phases with efficacious vascular
      enhancement in the different anatomic regions.

PMID- 20698805
TI  - Job strain, hypoxia and risk of amyotrophic lateral sclerosis: Results from a
      death certificate study.
AB  - Amyotrophic lateral sclerosis (ALS) most likely results from a multifactorial
      gene-environment interaction. Strenuous physical activity and occupational
      exposures have been suggested to play a role, and an abnormal response to hypoxia
      has been proposed in ALS pathogenesis. To test the hypothesis of an excess risk
      in occupations typically leading to intermittent hypoxia at the tissue level, we
      accessed a large publicly available database, including death certificates from
      24 U.S. states in 1984-1998. We conducted a case-control analysis of 14,628
      deaths due to ALS therein reported and 58,512 controls deceased from other
      selected causes of death, frequency matched by age, gender and broad geographic
      area. ALS risk associated with physical activity, and occupations leading to
      intermittent hypoxia, such as fire fighters and professional athletes, were
      calculated with unconditional logistic regression, adjusting by age, marital
      status, residence, and socioeconomic status. Physical activity in general did not
      show an association with ALS risk. Risk associated with occupation as a
      professional athlete was elevated (OR = 1.81, 99% CI 0.69-4.78), but not
      significantly so. Fire fighters showed a significant two-fold excess ALS risk (OR
      = 2.0; 99% CI 1.2-3.2). Based on our findings and the current clinical,
      epidemiological and experimental evidence, we suggest that occupational
      conditions typically leading to intermittent hypoxia, such as fire fighting,
      might be an ALS risk factor in subjects genetically prone to an abnormal response
      to hypoxia.

PMID- 20698806
TI  - Variation in the neurophysiological examination of amyotrophic lateral sclerosis
      in Europe.
AB  - Our objective was to analyse how patients with amyotrophic lateral sclerosis
      (ALS) are examined neurophysiologically at different European centres in order to
      identify possible areas with variation or disagreement in the neurophysiological
      examination of ALS. Ninety-three prospectively collected examinations from six
      out of seven neurophysiologists in the European ESTEEM project were analysed. All
      examinations were peer reviewed with an electromyographic consensus diagnosis of
      motor neuron disease and the diagnosis of ALS confirmed by clinical follow-up.
      The examinations were analysed for differences among the physicians in EMG
      techniques and number and distribution of examined and abnormal muscles and nerve
      segments. Considerable variation was found among the physicians regarding the
      average numbers of performed and abnormal EMG and nerve conduction studies per
      patient, the EMG techniques used, and the topographical distribution of the
      examined muscles. The existence of two different examination approaches, one with
      quantitative EMG analyses and relatively few muscles studied, and one with more
      muscles studied using qualitative methods was clearly confirmed in the present
      study. The large variation among the physicians indicates that different criteria
      were used, or that criteria were used inconsistently.

PMID- 20698808
TI  - A phase I, pharmacokinetic, dosage escalation study of creatine monohydrate in
      subjects with amyotrophic lateral sclerosis.
AB  - Creatine monohydrate (creatine) has potential neuroprotective properties and is a
      commonly used supplement in amyotrophic lateral sclerosis (ALS) and other
      neurodegenerative disorders. Minimum therapeutic and maximum tolerated dosages of
      creatine are not yet known, nor is it known what systemic plasma concentrations
      result from specific dosage regimens. The objectives of this study were to
      establish steady-state plasma pharmacokinetics of creatine at several dosages,
      and to evaluate the effects of creatine on brain metabolites using proton
      magnetic resonance spectroscopy ((1)H-MRS). Six participants with ALS received
      creatine at three weekly escalating oral dosages (5, 10, and 15 g b.i.d.). Plasma
      creatine levels and MR spectra were obtained at baseline and with each dosage
      increase. Mean pre-dose steady-state creatine plasma concentrations were 20.3,
      39.3, and 61.5 ug/ml at 5, 10, and 15 g b.i.d., respectively. Creatine spectra
      increased by 8% (p = 0.06) and glutamate + glutamine signals decreased by 17% (p
      = 0.039) at higher dosages. There were no safety concerns at any of the dosages.
      In conclusion, creatine plasma concentrations increased in a dose-dependent
      manner. Creatine appears to cross the blood-brain barrier, and oral
      administration of 15 g b.i.d. is associated with increased in vivo brain creatine
      concentrations and decreased glutamate concentrations.

PMID- 20698809
TI  - Clinical Phase I study with an Insulin-like Growth Factor-1 receptor inhibitor:
      experiences in patients with squamous non-small cell lung carcinoma.
AB  - BACKGROUND: Inhibition of the Insulin-like Growth Factor-1 receptor (IGF-1R) has
      resulted in extensive anti-tumor effects. Picropdophyllin (PPP, AXL1717) is a
      small-molecule inhibitor of the IGF-1R without inhibition of closely related
      receptors including the insulin receptor and has shown extensive effects against
      a wide range of tumors in animals. PPP is currently tested as an orally
      administrated single agent treatment in an open-label combined Phase I/II
      clinical study in advanced cancer patients with solid tumors which progress in
      spite of several lines of treatment. PATIENTS AND METHODS: The first part (Phase
      IA) consisted of single day BID dosing every three weeks with consecutive dose
      escalations. The second part (Phase IB) consists of seven days or longer BID
      dosing every three weeks, dosing range being 520-700 mg BID. Non-progressing
      patients could continue treatment within a compassionate use setting. RESULTS AND
      DISCUSSION: The present report describes our experience with the four patients
      with progressive squamous non-small cell lung cancer (NSCLC) that have received
      treatment with PPP. Despite more than seven months of PPP treatment as third or
      fourth line treatment, the reported patients did not develop any additional
      metastases. Furthermore, CT scans as well as (18)FDG-Positron Emission Tomography
      (PET) scans of the patients demonstrated large central necrotic areas, which may
      suggest tumor response. At the same time, the study drug is so far well
      tolerated. The phenomenon of necrosis in the tumors suggestive of tumor response
      has not been reported before in anti-IGF-1R treatment and will be subject to
      further studies in the present clinical trial.

PMID- 20698807
TI  - The epidemiology and treatment of ALS: focus on the heterogeneity of the disease
      and critical appraisal of therapeutic trials.
AB  - Abstract Effective treatments for amyotrophic lateral sclerosis (ALS) have
      remained elusive. Only riluzole, a drug thought to affect glutamate metabolism,
      improves survival albeit to modest extent. Explanations for the negative results
      of therapeutic trials include a likely heterogeneity, both in disease
      susceptibility and pathogenic mechanisms, and faulty methodology of clinical
      trials. Further understanding of these factors will lead to improvements in
      patient stratification, and in the design of future clinical trials.

PMID- 20698810
TI  - Standardized FDG uptake as a prognostic variable and as a predictor of incomplete
      cytoreduction in primary advanced ovarian cancer.
AB  - INTRODUCTION: In patients with advanced ovarian cancer undergoing preoperative
      PET/CT, we investigated the prognostic value of SUV in the primary tumor and we
      evaluated the value of SUV for predicting incomplete primary cytoreduction
      (macroscopic residual tumor). MATERIAL AND METHODS: From September 2004 to August
      2007, 201 consecutive patients with a pelvic tumor and a Risk of Malignancy Index
      (RMI) > 150 based on serum CA-125, ultrasound examinations and menopausal state,
      underwent PET/CT within two weeks prior to standard surgery/debulking of a pelvic
      tumor. At two-year follow-up (August 15, 2009) the association between SUV and
      overall survival/cytoreductive result were analyzed in 60 ovarian cancer patients
      (58 stage III and two stage IV). RESULTS: At inclusion median age was 62 years
      (range 35-85 years); 97% (58/60) had a performance status <=2; 42% (25/60)
      underwent complete debulking (no macroscopic residual tumor); median SUV(max) was
      13.5 (range 2.5-39.0). Median follow-up was 30.2 months. At follow-up 57% (34/60)
      were alive and 43% (26/60) had died from ovarian cancer. SUV(max) in patients
      alive was not statistically different from SUV(max) in dead patients (p=0.69),
      and SUV(max) was not correlated with the amount of residual tumor after surgery
      (p=0.19). Using univariate Cox regression analysis, residual tumor was a
      significant prognostic variable (p=0.001); SUV(max) was not a statistically
      significant prognostic variable (p=0.86). DISCUSSION: FDG uptake (SUV(max)) in
      the primary tumor of patients with advanced ovarian cancer was not a prognostic
      variable and the FDG uptake did not predict complete cytoreduction after primary
      surgery. Future prospective clinical trials will need to clarify if other PET
      tracers can serve as prognostic variables in ovarian cancer.

PMID- 20698811
TI  - Steroids in regional analgesia.
AB  - IMPORTANCE OF THE FIELD: Local injections of steroids have been widely practiced
      to provide regional analgesia for the treatment of a wide variety of
      musculoskeletal pain syndromes. However, evidence regarding the effectiveness of
      steroid injections is not substantial. Also, there have been reports of
      catastrophic complications associated with their use. AREAS COVERED IN THIS
      REVIEW: The evidence currently available in the literature (Database: Ovid
      MEDLINE 1950 to 2010) is reviewed. The areas covered include the analgesic
      mechanisms of steroids, indications for steroid injections and their
      effectiveness, as well as the risks and precautions for steroid injections. WHAT
      THE READER WILL GAIN: This is an up-to-date review on the clinical application of
      steroid injections for regional analgesia, which will give the reader an insight
      on how to maximize the benefits of steroids while minimizing their side effects
      and complications. TAKE HOME MESSAGE: Although steroid injections are generally
      considered effective and safe in the treatment of painful condition of limbs,
      their use in the treatment of chronic back pain is still controversial and
      serious complications have been reported. More studies on outcome and safety are
      warranted.

PMID- 20698812
TI  - Prolyl hydroxylase domain-containing protein inhibitors as stabilizers of hypoxia
      inducible factor: small molecule-based therapeutics for anemia.
AB  - IMPORTANCE OF THE FIELD: Anemia caused by chronic kidney disease and other
      chronic diseases or conditions can be managed by the treatment of biologic-based
      erythropoiesis stimulating agents (ESAs). Although these ESAs are successful in
      treating these anemic conditions, a small molecule-based anti-anemia medicine can
      potentially revolutionize the treatment of anemia by bringing convenience to
      patients and being cost effective. Prolyl hydroxylase domain-containing protein
      (PHD) inhibitors may provide an opportunity for the development of small molecule
      anti-anemia medicines. AREAS COVERED IN THIS REVIEW: This review covers efforts
      to target PHD enzymes for stabilization of hypoxia-inducible factor (HIF)-alpha
      subunits under normal oxygen levels as an attractive strategy to upregulate the
      expression of erythropoietin and genes involved in iron metabolism for the
      treatment of anemia. WHAT THE READER WILL GAIN: The reader will gain a brief
      summary of recent advances in HIF and PHD biology and a review of patents/patent
      applications on the subject of PHD inhibitors as HIF stabilizers for the
      treatment of anemia. TAKE HOME MESSAGE: Several classes of PHD enzyme inhibitors
      have been disclosed and several are currently in clinical trials for the
      development of small molecule-based therapeutics for the treatment of anemia.

PMID- 20698813
TI  - Therapeutic potential of the original incretin hormone glucose-dependent
      insulinotropic polypeptide: diabetes, obesity, osteoporosis and Alzheimer's
      disease?
AB  - IMPORTANCE TO THE FIELD: Glucose-dependent insulinotropic polypeptide (GIP) is an
      incretin hormone that potentiates nutrient-induced insulin release. To date, the
      physiological importance of GIP has received much less attention than its younger
      sister incretin hormone glucagon-like peptide-1. Thus, it is worthwhile to
      refocus on this important and somewhat neglected incretin hormone. AREAS COVERED
      IN THIS REVIEW: The potential role of GIP as a treatment option for type 2
      diabetes is highlighted. Furthermore, the use of GIP as a new therapeutic option
      for obesity, osteoporosis and cognitive impairment is also considered. WHAT THE
      READER WILL GAIN: Long-acting GIP receptor agonists offer a potential new class
      of antidiabetic drugs. Furthermore, recent observations suggest an as yet
      untapped potential for GIP agonists in the treatment of osteoporosis and
      cognitive impairment. In addition, GIP is known to play a role in lipid
      metabolism and fat deposition. Accordingly, both genetic and chemical ablation of
      GIP signalling in mice with obesity-diabetes can protect against, or reverse,
      many of the obesity-associated metabolic disturbances. This review focuses on
      preclinical data generated to date. TAKE HOME MESSAGE: GIP-based therapeutics
      have potential for the treatment of type 2 diabetes and obesity, with the
      possibility of further beneficial actions in osteoporosis and cognitive decline.

PMID- 20698814
TI  - New antibiotics for selective treatment of gastrointestinal infection caused by
      Clostridium difficile.
AB  - IMPORTANCE OF THE FIELD: Clostridium difficile infection (CDI) is associated with
      consumption of antibiotics which disrupt the normal microbial flora of the gut,
      allowing C. difficile to establish itself and produce disease. Currently, only
      vancomycin or metronidazole are recommended for treatment and many patients
      suffer from relapse on infection. Hence, there is a need for new treatment
      options. AREAS COVERED IN THIS REVIEW: This review evaluates five agents in
      development where the focus is on treatment of CDI. WHAT THE READER WILL GAIN:
      This review gives up-to-date information on fidaxomicin, REP3123, oritavancin,
      NVB302 and nitazoxanide and their likelihood of being licensed for the treatment
      of CDI. TAKE HOME MESSAGE: One agent, fidaxomicin, has undergone Phase III
      clinical trials which show it to be a promising new agent for the treatment of
      CDI with a low rate of relapse. Nitazoxanide is licensed for the treatment of
      parasitic intestinal infections but is not licensed for CDI. However, in small
      scale clinical trials it has been shown to have activity comparable to that of
      vancomycin and metronidazole. The other agents are all at early stages of
      development and clinical trials to evaluate their therapeutic potential for CDI
      have not yet been undertaken.

PMID- 20698815
TI  - Areca-nut extract modulates antigen-specific immunity and augments inflammation
      in ovalbumin-sensitized mice.
AB  - Areca-nut chewing has been linked to oral cancer and many other diseases, in
      which immune deterioration and tissue inflammation are plausibly involved. Recent
      studies reported that areca-nut extract (ANE) affected the functionality of
      lymphocytes and neutrophils in vitro. In the present study, we investigated the
      immunomodulatory effect of ANE in vivo. Ovalbumin (OVA)-sensitized mice were
      daily administered with ANE (5-50 mg/kg) for 10 doses by intraperitoneal
      injection from days 1 to 5 and from 8 to 12. The mice were systemically
      sensitized with OVA on day 3, and their footpads were challenged with OVA to
      induce delayed-type hypersensitivity (DTH) reactions on day 13. The serum level
      of OVA-specific IgM and IgG(1) was significantly attenuated by 5 and 25 mg/kg of
      ANE, whereas OVA-specific IgG(2a) was markedly enhanced by 50 mg/kg of ANE. The
      production of interferon (IFN)-gamma by splenocytes reexposed to OVA in culture
      was markedly augmented by ANE (25 and 50 mg/kg). In addition, ANE (25 and 50
      mg/kg) demonstrated an enhancing effect on DTH reactions, including the tissue
      swelling, the infiltration of CD3(+) and F4/80(+) cells, and the expression of
      IFN-gamma and tumor necrosis factor (TNF)-alpha in the footpads challenged with
      OVA. The phagocytic activity and TNF-alpha production by the splenic CD11b(+)
      cells were also enhanced in ANE-treated groups. Taken together, these results
      demonstrated that ANE modulated antigen-specific immune responses and promoted
      inflammatory reactions in vivo, which may contribute to immune deregulation
      associated with areca-related diseases.

PMID- 20698816
TI  - A further review of inhalation studies with cigarette smoke and lung cancer in
      experimental animals, including transgenic mice.
AB  - CONTEXT: The lack of an effective animal model for pulmonary carcinogenesis in
      smokers is a continuing problem for researchers trying to design Potentially
      Reduced Risk Products for those smokers who are either unwilling or unable to
      quit smoking. The major failing of inhalation assays with cigarette smoke in
      laboratory animals is that these assays produce only small percentages of animals
      with pulmonary tumors (e.g. adenomas, with the occasional adenocarcinoma), as
      opposed to the highly invasive carcinomas (e.g. small cell and squamous cell)
      seen in smokers. OBJECTIVE: To update previous reviews on animal models, and to
      add different types of transgenic (Tg) mice to the review. METHODS: Reviews were
      made of articles retrieved from PubMed and elsewhere. RESULTS: The addition of Tg
      mice to the arsenal of tests used for the evaluation of the carcinogenic
      potential of cigarettes did not result in any better understanding of the
      inability of such testing to reflect the epidemiological evidence for lung cancer
      in smokers. CONCLUSION: As in previous reviews on the subject, the best assay
      providing support for the epidemiology data is still the 5-month whole-body
      exposure of male A/J mice to a combination of mainstream/sidestream smoke,
      followed by a 4-month recovery.

PMID- 20698817
TI  - The multifactorial nature of Alzheimer's disease and related therapeutic
      strategies.

PMID- 20698818
TI  - Cell death targets and potential modulators in Alzheimer's disease.
AB  - Apoptosis is now recognized as a normal feature in the development of the nervous
      system and may also play a role in neurodegenerative disorders, such as
      Alzheimer's disease. Cell surface receptors, caspases, mitochondrial factors or
      p53 participate in the modulation and execution of cell death. Therefore, the
      ability to understand and manipulate the cell death machinery is an obvious goal
      of medical research. Potential therapeutic approaches to modulate disease by
      regulating apoptosis are being tested, and include the traditional use of small
      molecules to target specific players in the apoptosis cascade. As our
      understanding of apoptosis increases, further opportunities will arise for more
      specific therapies that will result in improved efficacy. This review focuses on
      molecular mechanisms of apoptosis in Alzheimer's disease and highlights the
      potential use of small molecule modulators to treat neurodegenerative disorders.

PMID- 20698819
TI  - Nitric oxide: target for therapeutic strategies in Alzheimer's disease.
AB  - Alzheimer's disease (AD) constitutes a progressive neurodegenerative disorder and
      the main cause of dementia. Numerous studies have focused on the pathogenic
      mechanism of AD to cure or prevent this devastating disease. But, despite recent
      advances, our understanding on the pathophysiology of this genetically complex
      and heterogeneous disorder is rather limited and treatment of the disease
      consists of medications to control the symptoms. Acetylcholinesterase inhibitors
      and N-methyl-D-aspartate (NMDA) receptor antagonists are the only available
      treatments recommended to manage the cognitive deficits caused by the disease.
      Therefore, the production of new drugs that may be able to cure the underlying
      cause of this chronic disease, not just the symptoms, is a matter of clinical
      interest. There is data implicating nitric oxide (NO) in the progression of the
      disease. The three isoforms of the NO-synthesizing enzyme (NOS) operate as
      central mediators of amyloid beta-peptide (Abeta) action, giving rise to elevated
      levels of NO that contributes to the maintenance, self-perpetuation and
      progression of the disease. Reducing Abeta production and the cholinergic deficit
      is a goal in the treatment of AD. In addition, a possible way to delay the
      progression of the illness must include a rationale design of enzyme inhibitors,
      subtype selective, targeting NOS isoforms implicated in damage to brain cells in
      AD. We are now presenting an overview regarding approved drugs for AD treatment
      and substances that although are not in use for the treatment of AD, including
      NOS inhibitors, may represent useful tools to unravel the pathophysiologic enigma
      of AD.

PMID- 20698820
TI  - Neuroinflammation, oxidative stress and the pathogenesis of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most common neurodegenerative disorder that
      affects the elderly. The increase of life-expectancy is transforming AD into a
      major health-care problem. AD is characterized by a progressive impairment of
      memory and other cognitive skills leading to dementia. The major pathogenic
      factor associated to AD seems to be amyloid-beta peptide (Abeta) oligomers that
      tend to accumulate extracellularly as amyloid deposits and are associated with
      reactive microglia and astrocytes as well as with degeneration of neuronal
      processes. The involvement of microglia and astrocytes in the onset and progress
      of neurodegenerative process in AD is becoming increasingly recognized, albeit it
      is commonly accepted that neuroinflammation and oxidative stress can have both
      detrimental and beneficial influences on the neural tissue. However, little is
      known about the interplay of microglia, astrocytes and neurons in response to
      Abeta, especially in the early phases of AD. This review discusses current
      knowledge about the involvement of neuroinflammation in AD pathogenesis, focusing
      on phenotypic and functional responses of microglia, astrocytes and neurons in
      this process. The abnormal production by glia cells of pro-inflammatory
      cytokines, chemokines and the complement system, as well as reactive oxygen and
      nitrogen species, can disrupt nerve terminals activity causing dysfunction and
      loss of synapses, which correlates with memory decline; these are phenomena
      preceding the neuronal death associated with late stages of AD. Thus, therapeutic
      strategies directed at controlling the activation of microglia and astrocytes and
      the excessive production of pro-inflammatory and pro-oxidant factors may be
      valuable to control neurodegeneration in dementia.

PMID- 20698821
TI  - Neurotoxicity of beta-amyloid protein: oligomerization, channel formation, and
      calcium dyshomeostasis.
AB  - Numerous studies have indicated that Alzheimer's amyloid-beta protein (Abeta)
      causes the degeneration of synapses and neurons, finally inducing the
      pathogenesis of Alzheimer's disease (AD). Recent approaches have emphasized the
      importance of Abeta oligomerization which enhances its neurotoxicity and
      synaptotoxicity. Our work as well as other groups' research have demonstrated
      that Abeta oligomers are directly incorporated into neuronal membranes and form
      calcium-permeable ion channels (amyloid channels). Although the precise molecular
      mechanism of Abeta neurotoxicity remains elusive, the formation of amyloid
      channels and the resultant abnormal elevation of the intracellular calcium levels
      might be the primary event for neurodegeneration, considering that calcium
      dyshomeostasis triggers various apoptotic pathways. This article reviews the
      current understanding of AD pathology based on the hypothesis that the disruption
      of calcium homeostasis through amyloid channels may be the molecular basis of
      Abeta neurotoxicity. The potential development of preventive agents for new
      therapeutic targets is also discussed.

PMID- 20698822
TI  - Monoamine oxidase inhibitors as neuroprotective agents in age-dependent
      neurodegenerative disorders.
AB  - Alzheimer's and Parkinson's diseases are the most common neurodegenerative
      disorders among the aged. The etiologies of these diseases remain to be
      clarified, but the common disease-modifying factors are confirmed: oxidative
      stress, apoptosis, mitochondrial dysfunction, excitotoxicity, impaired ubiquitine
      proteasome system and inflammation. Neuroprotective therapy is proposed to
      prevent the disease progression by intervening the pathogenic and disease
      modifying factors. From the studies on Parkinson's disease, the inhibitors of
      type B monoamine oxidase, such as selegiline and rasagiline, are the most
      promising neuroprotective agents to date. These inhibitors protect neuronal cells
      against cell death induced in cellular and animal models. The neuroprotective
      functions are ascribed to the stabilization of mitochondria, the prevention of
      death signaling process and the induction of pro-survival anti-apoptotic Bcl-2
      protein family and neurotrophic factors. In cellular models, selegiline and
      rasagiline increased the different neurotrophic factors classes, neurotrophins
      (nerve growth factor, brain-derive neurotrophic factor, neurotrophin 3) and
      ligands of glial cell line-derived neurotrophic factor, respectively. Studies in
      non-human primates and patients with Parkinson's disease confirmed further the
      induction of these specified neurotrophic factors. Selegiline and rasagiline are
      expected to show distinct pharmaceutical activities in selective neuronal systems
      through induction of distinct neurotrophic factors, and then activation of their
      own receptors and kinase systems. This review presents the molecular mechanisms
      behind neuroprotection by monoamine oxidase inhibitors and discusses the possible
      development of new drugs to prevent, delay and restore the neuronal cell death in
      Alzheimer's and Parkinson's diseases.

PMID- 20698823
TI  - Glycogen synthase kinase-3 (GSK-3) inhibitors for the treatment of Alzheimer's
      disease.
AB  - Originally discovered because of its role in the regulation of glucose
      metabolism, Glycogen Synthase Kinase-3 (GSK-3) it is now recognised as a crucial
      player in a diverse series of cellular processes involved in Alzheimer's disease
      (AD) pathology. Besides having been identified as the major tau protein kinase,
      GSK-3 mediates Abeta neurotoxicity, plays an essential role in synaptic
      plasticity and memory, might be involved in Abeta formation, and it has an
      important role in inflammation and neuronal survival, all key features of AD
      neuropathology. Moreover, AD was one of the earliest disorders linked to GSK-3
      dysfunction. Thus, the discovery of small molecule GSK-3 inhibitors has attracted
      significant attention to the protein both as therapeutic target for the
      therapeutic intervention in neurodegenerative diseases as well as a means to
      understand the molecular basis of these disorders.

PMID- 20698824
TI  - Structural determinants of the multifunctional profile of dual binding site
      acetylcholinesterase inhibitors as anti-Alzheimer agents.
AB  - Dual binding site acetylcholinesterase inhibitors have recently emerged as a new
      class of anti-Alzheimer agents with potential to positively modify the course of
      the disease. These compounds exhibit a multifunctional pharmacological profile
      arising from interaction with several biological targets involved upstream and
      downstream in the neurodegenerative cascade of Alzheimer's disease (AD). The
      primary target of these compounds is the enzyme acetylcholinesterase (AChE).
      Interaction of dual binding site AChE inhibitors with AChE results in a potent
      inhibitory activity of AChE and AChE-induced beta-amyloid peptide (Abeta)
      aggregation. Some dual binding site AChE inhibitors take on added value a
      significant ability to additionally inhibit the enzymes butyrylcholinesterase and
      BACE-1, involved in the co-regulation of the hydrolysis of the neurotransmitter
      acetylcholine and in Abeta formation, respectively. The structural determinants
      which mediate the interaction of dual binding site AChE inhibitors with these
      three important enzymes for AD treatment are herein reviewed.

PMID- 20698825
TI  - Epidermal growth factor receptor as a target for anti-cancer agent design.
AB  - The epidermal growth factor (EGF) receptors, one family of protein tyrosine
      kinases (PTK), are promising targets for the cancer therapy. Many potential
      inhibitors including monoclonal antibodies (mAbs), reversible inhibitors and
      irreversible inhibitors have been developed. Some of them have been approved by
      the FDA or in the stage of clinical trials. This report reviews the recent
      progress of the structures, functions and inhibitors of the epidermal growth
      factor receptor tyrosine kinases.

PMID- 20698826
TI  - Obesity modulation - the role in carcinogenesis.
AB  - Obesity has been recognized as an important risk factor for many serious medical
      conditions. The association of obesity with an increased risk of many cancers is
      of enormous economic importance to the health industry.The metabolic syndrome and
      visceral obesity have an increasing prevelance and incidence in the general
      population.The actual prevelance of the metabolic syndrome is 24% in US
      population and between 24,6% and 30.9% in Europe. Recent evidence from
      epidemiologic and basic research studies, as well as clinical and intervention
      studies, supports the emerging hypothesis that metabolic syndrome may be an
      important etiologic factor for the onset of cancer. In addition, increased body
      weight has recently been shown to be associated with an increased risk of cancers
      at multiple specific sites. The close interaction between cancer cells and
      adipocytes is an intriguing issue in tumor biology. In nowdays, several metabolic
      markers are implicated in the development and progression of several
      malignancies. This review describes the emerging data concerning the role of
      metabolic markes in tumor cell growth and relates them to their future clinical
      prospects.

PMID- 20698827
TI  - Impairment of F1F0-ATPase, adenine nucleotide translocator and adenylate kinase
      causes mitochondrial energy deficit in human skin fibroblasts with chromosome 21
      trisomy.
AB  - A central role for mitochondrial dysfunction has been proposed in the
      pathogenesis of DS (Down's syndrome), a multifactorial disorder caused by trisomy
      of human chromosome 21. To explore whether and how abnormalities in mitochondrial
      energy metabolism are involved in DS pathogenesis, we investigated the catalytic
      properties, gene expression and protein levels of certain proteins involved in
      mitochondrial ATP synthesis, such as F1F0-ATPase, ANT (adenine nucleotide
      translocator) and AK (adenylate kinase), in DS-HSF (human skin fibroblasts with
      trisomic karyotype), comparing them with euploid fibroblasts. In DS-HSF, we found
      a strong impairment of mitochondrial ATP synthesis due to a reduction in the
      catalytic efficiency of each of the investigated proteins. This impairment
      occurred in spite of unchanged gene expression and an increase in ANT and AK
      protein content, whereas the amount of ATPase subunits was selectively reduced.
      Interestingly, exposure of DS-HSF to dibutyryl-cAMP, a permanent derivative of
      cAMP, stimulated ANT, AK and ATPase activities, whereas H89, a specific PKA
      (protein kinase A) inhibitor, suppressed this cAMPdependent activation,
      indicating an involvement of the cAMP/PKA-mediated signalling pathway in the
      ATPase, ANT and AK deficit. Consistently, DS-HSF showed decreased basal levels of
      cAMP and reduced PKA activity. Despite the impairment of mitochondrial energy
      apparatus, no changes in cellular energy status, but increased basal levels of L
      lactate, were found in DS-HSF, which partially offset for the mitochondrial
      energy deficit by increasing glycolysis and mitochondrial mass.These results
      provide new insight into the molecular basis for mitochondrial dysfunction in DS
      and might provide a molecular explanation for some clinical features of the
      syndrome.

PMID- 20698828
TI  - Characterization of the kaurene oxidase CYP701A3, a multifunctional cytochrome
      P450 from gibberellin biosynthesis.
AB  - KO (kaurene oxidase) is a multifunctional cytochrome P450 catalysing three
      sequential oxidations in gibberellin phytohormone biosynthesis. These serve to
      transform the C4alpha methyl of the ent-kaurene olefin intermediate into the
      carboxylic acid moiety of ent-kauren-19-oic acid. To investigate the unknown
      catalytic mechanism and properties of KO, we have engineered the corresponding
      CYP701A3 from Arabidopsis thaliana (AtKO) for functional recombinant expression
      in Escherichia coli, involving use of a fully codon-optimized construct, along
      with additional N-terminal deletion and modification. This recombinant AtKO
      (rAtKO) was used to carry out 18O2 labelling studies with ent-kaurene, and the
      intermediates ent-kaurenol and ent-kaurenal, to investigate the multifunctional
      reaction sequence; revealing catalysis of three hydroxylation reactions, which
      further requires dehydration at some stage. Accordingly, following initial
      hydroxylation, ent-kaurenol must then be further hydroxylated to a gem-diol
      intermediate, and our data indicate that the subsequent reactions proceed via
      dehydration of the gem-diol to ent-kaurenal, followed by an additional
      hydroxylation to directly form ent-kaurenoic acid. Kinetic analysis indicates
      that these intermediates are all retained in the active site during the course of
      the reaction series, with the first hydroxylation being rate-limiting. In
      addition, investigation of alternative substrates demonstrated that ent-beyerene,
      which differs in ring structure distal to the C4alpha methyl, is only
      hydroxylated by rAtKO, indicating the importance of the exact tetracyclic ring
      structure of kaurane for multifunctional KO activity. Thus the results of the
      present study clarify the reaction sequence and enzymatic mechanism of KO, as
      well as substrate features critical for the catalysed multiple reaction sequence.

PMID- 20698829
TI  - Early onset giant retinal tear after posterior chamber phakic IOL.

PMID- 20698830
TI  - Twenty-five gauge vitrectomy for vitreous opacities secondary to ocular
      toxoplasmosis.

PMID- 20698831
TI  - Structural consequences after intravitreal bevacizumab injection without
      increasing apoptotic cell death in a retinopathy of prematurity mouse model.
AB  - PURPOSE: To evaluate the effect of different bevacizumab concentrations on
      retinal endothelial cell proliferation, retinal structures and apoptotic activity
      after intravitreal injection in a retinopathy of prematurity (ROP) mouse model.
      METHODS: A total of 35 of C57BL/J6 mice were exposed to 75+/-2% oxygen from
      postnatal day 7 to postnatal day 12. On day 12, 10 mice (group C) were injected
      with 2.5 MUg intravitreal bevacizumab (IVB), 11 mice (group D) were injected with
      1.25 MUg IVB, and 14 mice (group E) were injected with 0.625 MUg IVB in one eye.
      The contralateral eyes were injected with isotonic saline (control group=group
      B). Four nonexposed mice served as negative controls (group A).
      Neovascularization was quantified by counting the endothelial cell proliferation
      on the vitreal side of the inner limiting membrane of the retina. Histological
      and ultrastructural changes were examined by light and electron microscopy.
      Terminal deoxynucleotidyl transferase deoxy-UTP-nick end labelling (TUNEL) was
      used to detect apoptosis. RESULTS: The endothelial cell count per histological
      section was lower in groups C (p<0.0001), D (p<0.0001) and E (p<0.0001) compared
      with the control group B. Histological evaluation showed no retinal toxicity in
      any group. Electron microscopy revealed hyperoxia-induced mitochondrial
      dysmorphology in group B. Mitochondrial dysmorphology displayed dose-dependent
      gradual increase in IVB-injected eyes. Intravitreal bevacizumab induced no
      significant increase in apoptotic cell death. CONCLUSION: Bevacizumab suppresses
      endothelial cell proliferation in a ROP mouse model. In addition to hyperoxia
      induced mitochondrial dysmorphology of C57BL/J6 retina, morphological findings
      implicate further mitochondrial vulnerability because of bevacizumab without
      increase in apoptotic cell death.

PMID- 20698832
TI  - Adenosine sensitization after angiotensin II stimulation in afferent arterioles
      from normal rats does not occur during two-kidney, one-clip hypertension.
AB  - AIMS: G protein-coupled receptors such as the AT(1a) R are frequently subject to
      desensitization, extensively studied in cell culture but to small extent in
      hypertensive models. Recently, angiotensin II (ANG II)-induced desensitization
      was shown to last 10 min in isolated afferent arterioles (AAs), suggesting impact
      on ANG II vasoactivity. In the present study, we explored ANG II desensitization
      and effects of adenosine (Ado) in AAs from two-kidney, one-clip (2K1C)
      hypertensive rats. Our main hypothesis was that Ado affects ANG II contractility
      differently in 2K1C, because of persistently elevated levels of ANG II. METHODS:
      Afferent arterioles were isolated with the agarose-infusion/enzyme-treatment
      technique from normotensive and 2K1C hypertensive rats, and stimulated with ANG
      II (10(-7) M) at baseline and re-stimulated after 20 or 40 min, with or without
      Ado (2.5 * 10(-5) M) in the vessel bath. RESULTS: Afferent arterioles from
      normotensive rats re-stimulated with ANG II after 20 min displayed a blunted
      contraction (Delta12.8 +/- 4.3%, P < 0.05), which disappeared when AAs were
      stimulated after 40 min (Delta2.7 +/- 2.3%, NS), indicating that desensitization
      lasted for 30 +/- 10 min. Ado augmented ANG II contractions after 20 min, but not
      after 40 min, suggesting that only de-sensitized vessels were affected. Similar
      experiments in AAs from the clipped and non-clipped kidneys revealed no
      desensitization when re-stimulated with ANG II after 20 and 40 min, and
      contractions were unaffected by Ado. CONCLUSIONS: Reduced duration of
      desensitization in AAs from 2K1C may cause vessels to be sensitized longer and
      increase vasoconstriction. The present study demonstrates that Ado does not
      augment ANG II-induced contractions in AAs from 2K1C as in normotensive rats,
      possibly because of a reduced period of desensitization.

PMID- 20698833
TI  - Neuromuscular electrical stimulation improves GLUT-4 and morphological
      characteristics of skeletal muscle in rats with heart failure.
AB  - AIM: Changes in skeletal muscle morphology and metabolism are associated with
      limited functional capacity in heart failure, which can be attenuated by
      neuromuscular electrical stimulation (ES). The purpose of the present study was
      to analyse the effects of ES upon GLUT-4 protein content, fibre structure and
      vessel density of the skeletal muscle in a rat model of HF subsequent to
      myocardial infarction. METHODS: Forty-four male Wistar rats were assigned to one
      of four groups: sham (S), sham submitted to ES (S+ES), heart failure (HF) and
      heart failure submitted to ES (HF+ES). The rats in the ES groups were submitted
      to ES of the left leg during 20 days (2.5 kHz, once a day, 30 min, duty cycle 50%
      15 s contraction/15 s rest). After this period, the left tibialis anterior
      muscle was collected from all the rats for analysis. RESULTS: HF+ES rats showed
      lower values of lung congestion when compared with HF rats (P = 0.0001). Although
      muscle weight was lower in HF rats than in the S group, thus indicating
      hypotrophy, 20 days of ES led to their recovery (P < 0.0001). In both groups
      submitted to ES, there was an increase in muscle vessel density (P < 0.04).
      Additionally, heart failure determined a 49% reduction in GLUT-4 protein content
      (P < 0.03), which was recovered by ES (P < 0.01). CONCLUSION: In heart failure,
      ES improves morphological changes and raises GLUT-4 content in skeletal muscle.

PMID- 20698834
TI  - Epigenetic changes play critical role in age-associated dysfunctions of the
      liver.
AB  - CCAAT/Enhancer Binding Proteins family proteins are important regulators of liver
      functions. Here, we show the critical role of C/EBPalpha-mediated chromatin
      remodeling in the age-associated dysfunctions of the liver and in the maintenance
      of physiological homeostasis. Because ph-S193 isoform of C/EBPalpha is increased
      in livers of old mice, we have generated C/EBPalpha-S193D knockin mice, which
      mimic the ph-S193 isoform of C/EBPalpha. Analyses of these mice showed that the
      S193D mutation causes chromatin remodeling leading to histological appearance of
      'foci-like' nodules, which are also observed in livers of old mice. These 'foci
      like' structures contain K9 trimethylated histone H3, a marker of
      heterochromatin. The increase of heterochromatin regions in S193D mice correlates
      with the elevation of S193D-C/EBPalpha-HDAC1 complexes and with dys-regulation of
      gene expression including epigenetic silencing of cyclin D1 and D2 promoters and
      the inhibition of liver proliferation. The elimination of C/EBPalpha-HDAC1
      complexes in S193D mice by inhibition of HDAC1 corrects chromatin structure and
      normalizes expression of cyclin D1 and D2. We found that epigenetic dys
      regulation is also associated with the elevation of C/EBPbeta and with the
      increase of C/EBPalpha/beta heterodimers in S193D mice. The C/EBPalpha/beta
      heterodimers activate transcription of Glut4 and increase the levels of Glut4. As
      the result, S193D livers have accelerated uptake of glucose and accumulation of
      glycogen in the liver. Thus, this study demonstrates that the phosphorylation of
      C/EBPalpha at S193 leads to the appearance of heterochromatin regions, which
      correlates with the development of age-related dysfunctions of the liver.

PMID- 20698836
TI  - Differential regulation of NMDA receptor function by DJ-1 and PINK1.
AB  - Dysfunction of PTEN-induced kinase 1 (PINK1) or DJ-1 promotes neuronal death and
      is implicated in the pathogenesis of Parkinson's disease, but the underlying
      mechanisms remain unclear. Given the roles of N-methyl-d-aspartate receptor
      (NMDAr)-mediated neurotoxicity in various brain disorders including cerebral
      ischemia and neurodegenerative diseases, we investigated the effects of PINK1 and
      DJ-1 on NMDAr function. Using protein overexpression and knockdown approaches, we
      showed that PINK1 increased NMDAr-mediated whole-cell currents by enhancing the
      function of NR2A-containing NMDAr subtype (NR2ACNR). However, DJ-1 decreased
      NMDAr-mediated currents, which was mediated through the inhibition of both
      NR2ACNR and NR2B-containing NMDAr subtype (NR2BCNR). We revealed that the
      knockdown of DJ-1 enhanced PTEN expression, which not only potentiated NR2BCNR
      function but also increased PINK1 expression that led to NR2ACNR potentiation.
      These results indicate that NMDAr function is differentially regulated by DJ-1
      dependent signal pathways DJ-1/PTEN/NR2BCNR and DJ-1/PTEN/PINK1/NR2ACNR. Our
      results further showed that the suppression of DJ-1, while promoted NMDA-induced
      neuronal death through the overactivation of PTEN/NR2BCNR-dependent cell death
      pathway, induced a neuroprotective effect to counteract DJ-1 dysfunction-mediated
      neuronal death signaling through activating PTEN/PINK1/NR2ACNR cell survival
      promoting pathway. Thus, PINK1 acts with DJ-1 in a common pathway to regulate
      NMDAr-mediated neuronal death. This study suggests that the DJ-1/PTEN/NR2BCNR and
      DJ-1/PTEN/PINK1/NR2ACNR pathways may represent potential therapeutic targets for
      the development of neuroprotection strategy in the treatment of brain injuries
      and neurodegenerative diseases such as Parkinson's disease.

PMID- 20698835
TI  - Decreased oxidative stress and greater bone anabolism in the aged, when compared
      to the young, murine skeleton with parathyroid hormone administration.
AB  - Because of recent insights into the pathogenesis of age-related bone loss, we
      investigated whether intermittent parathyroid hormone (PTH) administration
      antagonizes the molecular mechanisms of the adverse effects of aging on bone.
      Parathyroid hormone produced a greater increase in vertebral trabecular bone
      mineral density and bone volume as well as a greater expansion of the
      endocortical bone surface in the femur of 26- when compared to 6 -month-old
      female C57BL/6 mice. Moreover, PTH increased trabecular connectivity in
      vertebrae, and the toughness of both vertebrae and femora in old, but not young,
      mice. Parathyroid hormone also increased the rate of bone formation and reduced
      osteoblast apoptosis to a greater extent in the old mice. Most strikingly, PTH
      reduced reactive oxygen species, p66(Shc) phosphorylation, and expression of the
      lipoxygenase Alox15, and it increased glutathione and stimulated Wnt signaling in
      bone of old mice. Parathyroid hormone also antagonized the effects of oxidative
      stress on p66(Shc) phosphorylation, Forkhead Box O transcriptional activity,
      osteoblast apoptosis, and Wnt signaling in vitro. In contrast, administration of
      the antioxidants N-acetyl cysteine or pegylated catalase reduced osteoblast
      progenitors and attenuated proliferation and Wnt signaling. These results suggest
      that PTH has a greater bone anabolic efficacy in old age because in addition to
      its other positive actions on bone formation, it antagonizes the age-associated
      increase in oxidative stress and its adverse effects on the birth and survival of
      osteoblasts. On the other hand, ordinary antioxidants cannot restore bone mass in
      old age because they slow remodeling and attenuate osteoblastogenesis by
      interfering with Wnt signaling.

PMID- 20698841
TI  - Perfluorocarbon-based oxygen carriers: review of products and trials.
AB  - A viable blood substitute is still of great necessity throughout the world.
      Perfluorocarbon-based oxygen carriers (PFCOCs) are emulsions that take advantage
      of the high solubility of respiratory gases in perfluorocarbons (PFCs). Despite
      attractive characteristics, no PFCOC is currently approved for clinical uses.
      Some PFCOCs have failed due to secondary effects of the surfactants employed,
      like Fluosol DA, whereas others to adverse cerebrovascular effects on
      cardiopulmonary bypass, such as Oxygent. Further in-depth, rigorous work is
      needed to overcome the annotated failures and to obtain a safe PFCOC approved for
      human use. The aim of this study is to review in detail the most-used PFCOCs,
      their formulation, and preclinical and clinical trials, and to reflect upon
      causes of failure and strategies to overcome such failures.

PMID- 20698837
TI  - A polymorphism in GABRA2 is associated with the medial frontal response to
      alcohol cues in an fMRI study.
AB  - BACKGROUND: Significant evidence has accumulated to suggest an association
      between single-nucleotide polymorphisms (SNPs) in the GABRA2 gene and alcoholism.
      However, research has yet to show an association between these polymorphisms and
      the human brain's reward system function. In this study, we stratified subjects
      who had participated in an fMRI study of alcohol cue responses according to their
      genotype at a SNP in GABRA2 (rs279871) shown to be associated with alcohol
      dependence (Edenberg et al., 2004). METHODS: Genotyping showed 13 subjects to be
      homozygous for the high-risk allele (AA), and 23 subjects to be heterozygous
      (AG). In fMRI, subjects were exposed to the aromas of their preferred alcoholic
      drink odors (AO), as well as to appetitive control odors (ApCO) under both
      alcohol intoxication and placebo control conditions. RESULTS: Homozygous AA
      subjects had a larger [AO > ApCO] response than did AG subjects in medial frontal
      cortical areas thought to code reward value. However, AG subjects had a larger
      [AO > ApCO] effect in the ventral tegmental area. Alcohol intoxication did not
      alter these group differences. CONCLUSIONS: These are the first data to suggest
      that GABRA2 genotype could affect the brain's responses to cues associated with
      alcohol.

PMID- 20698842
TI  - Application of polycaprolactone as an anti-adhesion biomaterial film.
AB  - Adhesions are unavoidable consequences of surgery and other trauma. How to
      prevent the adhesions remains a big issue in healthcare system. The objective of
      this study is to test the efficacy of polycaprolactone (PCL) films as physical
      barriers in reducing postoperative intra-abdominal adhesions in the rat cecum
      abdominal wall model. PCL is quite cheap compared with the agents recently used
      in the market. The fabrication method is also very easy to perform. Scanning
      electron microscope (SEM) showed multiple pores over upper and bottom surfaces
      but too small to permit cells to migrate from one surface onto another surface.
      Those pores were proven to be not interconnected. The PCL film did not show any
      evidence of cytotoxic effects as it did not induce any significant increase in
      cytoplasmic lactate dehydrogenase release from the NIH3T3 cells that it came in
      contact with. In animal studies, the PCL films led to fewer adhesions than
      Seprafilm in rat adhesion model. PCL films were efficacious in reducing
      postoperative intra-abdominal adhesion formation in rat cecum-abdominal wall
      models.

PMID- 20698843
TI  - Novel approach to gene expression profiling in Sezary  syndrome.
AB  - BACKGROUND: Microarray hybridization studies in Sezary syndrome (SS) have
      compared T lymphocytes from patients with cutaneous T-cell lymphoma with those of
      normal controls; a major limitation of this design is that significant inherent
      genetic variability of lymphocyte populations between individuals may produce
      differences in gene expression unrelated to disease state. OBJECTIVE: The
      objective of this study was to minimize the heterogeneity of information derived
      from whole-genome expression analysis and to identify specific genetic
      differences between highly purified malignant and nonmalignant (control) T cells
      from the same patient with SS. METHODS: Peripheral blood mononuclear cells were
      obtained from a patient with SS, stained with anti-T-cell receptor Vb (TCR-Vb)
      antibodies, and sorted by multiparameter flow cytometry. Malignant cells
      expressed the dominant TCR-Vb; control T cells lacked the dominant TCR-Vb but
      were otherwise phenotypically identical (CD3+CD4+CD45RO+). These cell populations
      were compared using the Illumina Inc. Sentrix Human-6 expression BeadChip system.
      RESULTS: Transcriptome analysis using the J5 test, which was selected for data
      analysis based on an efficiency analysis of competing statistical methods, showed
      differential expression of 44 genes between the malignant and nonmalignant cell
      subsets. Promyelocytic leukaemia zinc finger protein (ZBTB16) was the most
      profoundly upregulated gene in the malignant cell population, while interferon
      regulatory factor 3 (IRF3) and interferon-induced protein 35 (IFI35), which are
      important elements of the cellular response to viral infection, were
      significantly downregulated. CONCLUSIONS: The results of this study suggest the
      feasibility of this novel comparative approach to genomic profiling in SS. Using
      this method, we identified several differentially expressed genes and pathways
      not previously described in SS. While these findings require validation in larger
      studies, they may be important in SS pathogenesis.

PMID- 20698844
TI  - Skin responses to topical dehydroepiandrosterone: implications in antiageing
      treatment?
AB  - BACKGROUND: Although low dehydroepiandrosterone (DHEA) is suspected to have a
      role in skin ageing, little information is available on the mechanisms
      potentially involved. OBJECTIVES: To obtain information on androgen receptor (AR)
      and procollagen expression in ageing skin during DHEA treatment. METHODS: A
      placebo-controlled, randomized, prospective study was performed with 75
      postmenopausal women aged 60-65 years. The women were treated twice daily for 13
      weeks with 3.0 mL of placebo or 0.1%, 0.3%, 1% or 2% DHEA cream applied on the
      face, arms, back of hands, upper chest and right thigh where 2-mm biopsies were
      collected before and after treatment. RESULTS: Although the overall structure of
      the epidermis was not significantly affected at the light microscopy level, AR
      expression examined by immunocytochemistry was markedly increased by DHEA
      treatment. In the dermis, the expression levels of procollagen 1 and 3 mRNA
      estimated by in situ hybridization were increased by DHEA treatment. In addition,
      the expression of heat shock protein (HSP) 47, a molecule believed to have
      chaperone-like functions potentially affecting procollagen biosynthesis, was also
      found by immunocytochemistry evaluation to be increased, especially at the two
      highest DHEA doses. CONCLUSION: These data suggest the possibility that topical
      DHEA could be used as an efficient and physiological antiageing skin agent.

PMID- 20698845
TI  - Transforming growth factor-beta enhances matrix metalloproteinase-2 expression
      and activity through AKT in fibroblasts derived from angiofibromas in patients
      with tuberous sclerosis complex.
AB  - BACKGROUND: Patients with tuberous sclerosis complex (TSC) develop fibrous
      tumours in the brain, skin, kidney, heart and lungs due to TSC1/2 mutations. In
      the skin, patients develop angiofibromas that have vascular and fibrotic
      components in which transforming growth factor (TGF)-beta and matrix
      metalloproteinase (MMP)-2 are important. OBJECTIVES: To investigate if the TGF
      beta axis and MMP-2 play an important role in the pathogenesis of TSC
      angiofibromas. METHODS: Samples from TSC angiofibromas and normal skin were
      measured for expression of TGF-beta and MMP-2 by immunohistochemistry and real
      time polymerase chain reaction. Fibroblasts grown from TSC angiofibromas (TSC
      fibroblasts) were incubated with TGF-beta. Expression of ERK, AKT and S6K was
      measured by Western blotting, and MMP-2 expression and activity were determined
      by enzyme-linked immunosorbent assay and gelatin zymography, respectively.
      RESULTS: There was an increase in the expression of TGF-beta and MMP-2 in TSC
      tumours compared with those in normal skin. The baseline expression of MMP-2 was
      increased in conditioned medium from TSC fibroblasts. In addition, TGF-beta
      enhanced MMP-2 production and activity, which could be abrogated by pretreatment
      with an AKT inhibitor (LY294002) but not with rapamycin. Finally, there was a
      significant colocalization of TGF-beta and MMP-2 in the TSC tumours. CONCLUSIONS:
      There is an increase of MMP-2 as a result of TGF-beta acting through AKT in TSC
      tumour cells. This regulation of the TGF-beta-AKT-MMP-2 axis is independent of
      mammalian target of rapamycin (mTOR) signalling. In addition to targeting the
      mTOR pathway, targeting TGF-beta simultaneously could block dysregulated tissue
      remodelling in TSC tumours.

PMID- 20698846
TI  - An unusual case of granulomatous cutaneous T-cell lymphoma showing
      subcutaneous/muscular involvement and a 5q33.1 deletion.

PMID- 20698847
TI  - Quetiapine in the treatment of hyperhidrosis axillaris.

PMID- 20698848
TI  - Deregulation of E-cadherin by human papillomavirus is not confined to high-risk,
      cancer-causing types.
AB  - BACKGROUND: E-cadherin is a tumour suppressor protein, which is normally
      expressed on keratinocytes and antigen-presenting Langerhans cells (LCs) in the
      epidermis. We have previously shown that E-cadherin is lost from tissues infected
      with the high-risk cancer-causing human papillomavirus (HPV) type 16. OBJECTIVES:
      To test if E-cadherin dysregulation is associated with the cancer risk of the
      infecting HPV and to establish if it is conserved among HPVs in the alpha, beta,
      gamma and MU genera. METHODS: Forty-seven lesions infected with low- or high-risk
      HPV types spanning four HPV genera were stained for E-cadherin, P-cadherin and
      CD1a to detect LCs. RESULTS: Surface E-cadherin was reduced in tissues infected
      with members of the alpha4, alpha7 and alpha9 species and the gamma and MU genera
      but was equivalent to normal epidermis in the beta only-infected lesions tested
      and patchy in alpha10-infected tissues. There was a direct relationship between
      atypical E-cadherin expression and a significant reduction in LCs. Expression of
      P-cadherin, a protein that is increased in the E-cadherin constitutive knockout
      mouse, was increased in lesions with reduced E-cadherin. CONCLUSIONS: These data
      show that E-cadherin dysregulation by HPV is widely conserved across the majority
      of HPV genera. E-cadherin expression was reduced or lost in epidermis
      irrespective of the cancer risk of the infecting HPV type or the ability of the
      virus to degrade retinoblastoma protein or p53. A correlation between
      dysregulated E-cadherin and reduced numbers of LCs supports viral regulation of
      surface E-cadherin contributing to viral evasion of the host immune system.

PMID- 20698849
TI  - The spectrum of histopathological features in acute generalized exanthematous
      pustulosis: a study of 102 cases.
AB  - BACKGROUND: Acute generalized exanthematous pustulosis (AGEP) is a rare severe
      pustular reaction pattern with a typical clinical picture. OBJECTIVES: To
      characterize the histopathological features of AGEP in a large series of cases
      with a validated diagnosis. METHODS; A multinational retrospective
      histopathological study was conducted. It included 102 hospitalized patients
      (recruited within the EuroSCAR and RegiSCAR studies) with a validated diagnosis
      of probable or definite AGEP. A systematic description of the histopathological
      features in AGEP was done based on a standardized grading system. RESULTS:
      Sub/intracorneal pustules (41%), intraepidermal pustules (20%) or combinations of
      them (38%) were observed in 102 cases. The pustules were usually large (> 15
      keratinocytes) (82% and 89%, respectively) and regularly contained eosinophils
      (36% and 32%, respectively). Spongiform features were less prominent in the
      sub/intracorneal pustules compared with the intraepidermal pustules (44% and 95%,
      respectively). The main epidermal features were necrotic keratinocytes (67%),
      including incidental segmental necrosis (7%), and spongiosis (80%) with
      neutrophil exocytosis (77%). The main dermal features were papillary oedema (88%)
      and mixed superficial (100%), interstitial (93%), and mid/deep-dermal infiltrates
      (95%) containing neutrophils (100%) and eosinophils (81%). Follicular pustules
      were also seen (23%), but vasculitis generally was absent. Classical features of
      plaque-type psoriasis were infrequent and usually mild. No significant
      differences were observed between a subgroup of 16 cases with and 86 cases
      without psoriasis. CONCLUSIONS: The present histopathological study concerns a
      large series of cases with a validated diagnosis of AGEP. It provides diagnostic
      clues in favour of AGEP in patients with a pustular eruption.

PMID- 20698850
TI  - Encoding a superantigen by Staphylococcus aureus does  not affect clinical
      characteristics of infected atopic  dermatitis lesions.
AB  - BACKGROUND: Bacterial infection with Staphylococcus aureus is a known trigger for
      the worsening of atopic dermatitis (AD). Staphylococcal superantigens have been
      theorized to make a potential contribution to this worsening of AD seen with
      infection. OBJECTIVES: We sought to assess whether encoding a superantigen by S.
      aureus affects the inflammatory characteristics of impetiginized AD skin lesions.
      METHODS: Fifty-two children with clinically impetiginized lesions of AD which
      were positive for S. aureus were enrolled in this study. A lesion was graded
      clinically using the Eczema Area and Severity Index (EASI), and then wash fluid
      was obtained from the lesion for quantitative bacterial culture, and measurement
      of bacterial products lipoteichoic acid and staphylococcal protein A and
      cytokines. The staphylococcal isolate was tested for antibiotic susceptibilities
      and the presence of a superantigen. RESULTS: Fifty-four per cent (28 of 52) of
      the staphylococcal isolates encoded a superantigen. The presence of a
      superantigen had no significant effect on EASI score, amounts of bacterial
      products or inflammatory cytokines in the AD lesion. CONCLUSIONS: These studies
      suggest that the expression of a superantigen by S. aureus alone does not play an
      important role in the increased skin inflammation associated with staphylococcal
      infection in childhood AD.

PMID- 20698851
TI  - Frontal fibrosing alopecia: a clinical review of 36 patients.
AB  - BACKGROUND: Frontal fibrosing alopecia (FFA) is a primary lymphocytic cicatricial
      alopecia with a distinctive clinical pattern of progressive frontotemporal
      hairline recession. Currently, there are no evidence-based studies to guide
      treatment for patients with FFA; thus, treatment options vary among clinicians.
      OBJECTIVES: We report clinical findings and treatment outcomes of 36 patients
      with FFA, the largest cohort to date. Further, we report the first evidence-based
      study of the efficacy of hydroxychloroquine in FFA using a quantitative clinical
      score, the Lichen Planopilaris Activity Index (LPPAI). METHODS: A retrospective
      case note review was performed of 36 adult patients with FFA. Data were collected
      on demographics and clinical findings. Treatment responses to hydroxychloroquine,
      doxycycline and mycophenolate mofetil were assessed using the LPPAI. Adverse
      events were monitored. RESULTS: Most patients in our cohort were female (97%),
      white (92%) and postmenopausal (83%). Apart from hairline recession, 75% also
      reported eyebrow loss. Scalp pruritus (67%) and perifollicular erythema (86%)
      were the most common presenting symptom and sign, respectively. A statistically
      significant reduction in signs and symptoms in subjects treated with
      hydroxychloroquine (P < 0.05) was found at both 6- and 12-month follow up.
      CONCLUSIONS: In FFA, hairline recession, scalp pruritus, perifollicular erythema
      and eyebrow loss are common at presentation. Despite the limitations of a
      retrospective review, our data reveal that hydroxychloroquine is significantly
      effective in reducing signs and symptoms of FFA after both 6 and 12 months of
      treatment. However, the lack of a significant reduction in signs and symptoms
      between 6 and 12 months indicates that the maximal benefits of hydroxychloroquine
      are evident within the first 6 months of use.

PMID- 20698852
TI  - Effect of experimental hyperlipidaemia on the electrocardiographic effects of
      repeated doses of halofantrine in rats.
AB  - BACKGROUND AND PURPOSE: Halofantrine can cause a prolongation of the cardiac QT
      interval, leading to serious ventricular arrhythmias. Hyperlipidaemia elevates
      plasma concentration of halofantrine and may influence its tissue uptake. The
      present study examined the effect of experimental hyperlipidaemia on QT interval
      prolongation induced by halofantrine in rats. EXPERIMENTAL APPROACH:
      Normolipidaemic and hyperlipidaemic rats (induced with poloxamer 407) were given
      4 doses of halofantrine (i.v., 4-40 mg.kg(-1).d(-1)) or vehicle every 12 h. Under
      brief anaesthesia, ECGs were recorded before administration of the vehicle or
      drug and 12 h after the first and last doses. Blood samples were taken at the
      same time after the first and last dose of halofantrine. Hearts were also
      collected 12 h after the last dose. Plasma and heart samples were assayed for
      drug and desbutylhalofantrine using a stereospecific method. KEY RESULTS: In the
      vehicle group, hyperlipidaemia by itself did not affect the ECG. Compared to
      baseline, QT intervals were significantly higher in both normolipidaemic and
      hyperlipidaemic rats after halofantrine. In hyperlipidaemic rats, plasma but not
      heart concentrations of the halofantrine enantiomers were significantly higher
      compared to those in normolipidaemic rats. Despite the lack of difference in the
      concentrations of halofantrine in heart, QT intervals were significantly higher
      in hyperlipidaemic compared to those in normolipidaemic rats. CONCLUSIONS AND
      IMPLICATIONS: The unbound fraction of halofantrine appeared to be the controlling
      factor for drug uptake by the heart. Our data suggested a greater vulnerability
      to halofantrine-induced QT interval prolongation in the hyperlipidaemic state.

PMID- 20698854
TI  - A new preclinical biomarker for risk of Torsades de Pointes: drug-induced
      reduction of the cardiac electromechanical window.
AB  - Evaluation of new therapeutic agents for their potential to cause QT interval
      prolongation and drug-induced ventricular arrhythmia, like Torsades de Pointes
      (TdP), is a critical activity during drug development. The QT interval has been
      used as a surrogate biomarker to assess ventricular repolarization effects caused
      by drug-induced blockade of cardiac repolarizing currents, mainly IKr, but is
      imperfect in predicting proarrhythmia. Evidence suggests that left ventricular
      mechanical dysfunction may also contribute to ventricular arrhythmias; thus,
      electrical and mechanical alterations may have a role in drug-induced TdP. The
      electromechanical window (EMw) represents the time difference between the end of
      electrical systole (i.e. the QT interval) and the completion of ventricular
      relaxation (i.e. the QLVPend interval), and appears to be a new potential
      biomarker for TdP risk. A reduction in the EMw (to negative values) has now been
      shown to be associated with the onset of TdP in an anaesthetized dog model of
      long QT1 syndrome. Therefore, the EMw represents a novel indicator of TdP risk
      that may add predictive value beyond assay of drug-induced QT interval
      prolongation.

PMID- 20698853
TI  - Japanese encephalitis virus induces matrix metalloproteinase-9 in rat brain
      astrocytes via NF-kappaB signalling dependent on MAPKs and reactive oxygen
      species.
AB  - BACKGROUND AND PURPOSE: Japanese encephalitis virus (JEV) is a member of the
      family Flaviviridae and JEV infection is a major cause of acute encephalopathy in
      children, which destroys cells in the CNS, including astrocytes and neurons.
      However, the detailed mechanisms underlying the inflammatory action of JEV are
      largely unclear. EXPERIMENTAL APPROACH: The effect of JEV on the expression of
      matrix metalloproteinase (MMP)-9 was determined by gelatin zymography, Western
      blot analysis, real-time PCR and promoter assay. The involvement of the NADPH
      oxidase and reactive oxygen species (ROS), MAPKs, and the transcription factor NF
      kappaB in these responses was investigated by using selective pharmacological
      inhibitors and transfection with appropriate siRNAs. KEY RESULTS: JEV induced the
      expression of the pro-form of MMP-9 in rat brain astrocytes (RBA-1 cells). In RBA
      1 cells, JEV induced MMP-9 expression and promoter activity, which was inhibited
      by pretreatment with inhibitors of NADPH oxidase (diphenylene iodonium chloride
      or apocynin), MAPKs (U0126, SB203580 or SP600125) and a ROS scavenger (N
      acetylcysteine), or transfection with siRNAs of p47(phox) , ERK1, JNK2 and p38.
      In addition, JEV-induced MMP-9 expression was reduced by pretreatment with an
      inhibitor of NF-kappaB (helenalin) or transfection with p65 siRNA. Moreover, JEV
      stimulated NF-kappaB activation was inhibited by pretreatment with the inhibitors
      of NADPH oxidase and MAPKs. CONCLUSIONS AND IMPLICATIONS: MMP-9 expression
      induced by JEV infection of RBA-1 cells was mediated through the generation of
      ROS and activation of p42/p44 MAPK, p38 MAPK and JNK1/2, leading to NF-kappaB
      activation.

PMID- 20698855
TI  - Cigarette smoke exposure up-regulates endothelin receptor B in human pulmonary
      artery endothelial cells: molecular and functional consequences.
AB  - BACKGROUND AND PURPOSE: Pulmonary arteries from smokers and chronic obstructive
      pulmonary disease patients show abnormal endothelium-dependent vascular
      reactivity. We studied the effect of cigarette smoke extract (CSE) on endothelin
      receptor B (ET(B) ) expression in human pulmonary artery endothelial cells
      (HPAECs) and its role in endothelial dysfunction. EXPERIMENTAL APPROACH: ET(B)
      receptor expression was measured by real time RT-PCR, Western blot and
      immunofluorescence. Cell contraction, intracellular Ca(2+) , F/G-actin, RhoA
      activity, myosin light chain phosphorylation, ET, NO, thromboxane (Tx)A(2) and
      reactive oxygen species (ROS) were measured by traction microscopy, fluorescence
      microscopy, phalloidin fluorescence, colorimetric assay, Western blot, elisa and
      DCFDA fluorescence respectively. KEY RESULTS: Cigarette smoke extract dose
      dependently increased ET(B) receptor expression in HPAECs after 24h incubation.
      CSE-induced ET(B) expression was attenuated by bosentan, the ET(B) receptor
      antagonist BQ788, the Rho kinase antagonist Y27632 and the antioxidant N
      acetylcysteine. A monoclonal antibody to ET-1 prevented CSE-induced ET(B)
      receptor overexpression. Twenty-four hour exposure to ET-1 dose-dependently
      increased ET(B) receptor expression, mimicking the effect of CSE. CSE-induced
      ET(B) receptor overexpression caused greater cell contraction; increased
      intracellular Ca(2+) ; increased F/G-actin and RhoA activity; increased myosin
      light chain phosphorylation; augmented TxA(2) and ROS production; and decreased
      NO after acute ET-1 (10nM). These effects were attenuated by bosentan, BQ788,
      Y27632 and N-acetylcysteine. CONCLUSIONS AND IMPLICATION: Cigarette smoke extract
      induced ET(B) receptor overexpression by a feed forward mechanism mediated partly
      by ET release, promoting HPAEC dysfunction and attenuated by ET(B) receptor
      blockade, Rho kinase and ROS inhibition. These results provide support for the
      use of bosentan in CS-related endothelial dysfunction.

PMID- 20698856
TI  - Utility of organotypic raphe slice cultures to investigate the effects of
      sustained exposure to selective 5-HT reuptake inhibitors on 5-HT release.
AB  - BACKGROUND AND PURPOSE: Selective 5-hydroxytryptamine (5-HT, serotonin) reuptake
      inhibitors (SSRIs) are widely used antidepressants and their therapeutic effect
      requires several weeks of drug administration. The delayed onset of SSRI efficacy
      is due to the slow neuroadaptive changes of the 5-hydroxytryptaminergic (5
      HTergic) system. In this study, we examined the acute and chronic effects of
      SSRIs on the 5-HTergic system using rat raphe slice cultures. EXPERIMENTAL
      APPROACH: For organotypic raphe slice cultures, mesencephalic coronal sections
      containing dorsal and median raphe nuclei were prepared from neonatal Wistar rats
      and cultured for 14-16 days. KEY RESULTS: Acute treatment with citalopram,
      paroxetine or fluoxetine (0.1-10 uM) in the slice cultures slightly increased
      extracellular 5-HT levels, while sustained exposure for 4 days augmented the
      elevation of 5-HT level in a time-dependent manner. Sustained exposure to
      citalopram had no effect on tissue contents of 5-HT and its metabolite,
      expression of tryptophan hydroxylase or the membrane expression of 5-HT
      transporters. The augmented 5-HT release was attenuated by Ca(2+) -free
      incubation medium or treatment with tetrodotoxin. Experiments with 5-HT(1A/B)
      receptor agonists and antagonists revealed that desensitization of 5-HT(1)
      autoreceptors was not involved in the augmentation of 5-HT release. Finally, co
      treatment with an alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
      (AMPA)/kainate, but not an N-methyl-d-aspartate, receptor antagonist, suppressed
      this augmentation. CONCLUSION AND IMPLICATIONS: These results suggest that
      sustained exposure to SSRIs induces the augmentation of exocytotic 5-HT release,
      which is caused, at least in part, by the activation of AMPA/kainate receptors in
      the raphe slice cultures.

PMID- 20698857
TI  - Activation of PDE2 and PDE5 by specific GAF ligands: delayed activation of PDE5.
AB  - BACKGROUND AND PURPOSE: By controlling intracellular cyclic nucleotide levels,
      phosphodiesterases (PDE) serve important functions within various signalling
      pathways. The PDE2 and PDE5 families are allosterically activated by their
      substrate cGMP via regulatory so-called GAF domains. Here, we set out to identify
      synthetic ligands for the GAF domains of PDE2 and PDE5. EXPERIMENTAL APPROACH:
      Using fluorophore-tagged, isolated GAF domains of PDE2 and PDE5, promising cGMP
      analogues were selected. Subsequently, the effects of these analogues on the
      enzymatic activity of PDE2 and PDE5 were analysed. KEY RESULTS: The PDE2 ligands
      identified, 5,6-DM-cBIMP and 5,6-DCl-cBIMP, caused pronounced, up to 40-fold
      increases of the cAMP- and cGMP-hydrolysing activities of PDE2. The ligand for
      the GAF domains of PDE5, 8-Br-cGMP, elicited a 20-fold GAF-dependent activation
      and moreover revealed a time-dependent increase in PDE5 activity that occurred
      independently of a GAF ligand. Although GAF-dependent PDE5 activation was fast at
      high ligand concentrations, it was slow at physiologically relevant cGMP
      concentrations; PDE5 reached its final catalytic rates at 1uM cGMP after
      approximately 10min. CONCLUSIONS AND IMPLICATIONS: We conclude that the delayed
      activation of PDE5 is required to shape biphasic, spike-like cGMP signals.
      Phosphorylation of PDE5 further enhances activity and conserves PDE5 activation,
      thereby enabling PDE5 to act as a molecular memory balancing cGMP responses to
      nitric oxide or natriuretic peptide signals.

PMID- 20698859
TI  - A family of intermediate filament-like proteins is sequentially assembled into
      the cytoskeleton of Toxoplasma gondii.
AB  - The intracellular protozoan parasite Toxoplasma gondii divides by a unique
      process of internal budding that involves the assembly of two daughter cells
      within the mother. The cytoskeleton of Toxoplasma, which is composed of
      microtubules associated with an inner membrane complex (IMC), has an important
      role in this process. The IMC, which is directly under the plasma membrane,
      contains a set of flattened membranous sacs lined on the cytoplasmic side by a
      network of filamentous proteins. This network contains a family of intermediate
      filament-like proteins or IMC proteins. In order to elucidate the division
      process, we have characterized a 14-member subfamily of Toxoplasma IMC proteins
      that share a repeat motif found in proteins associated with the cortical alveoli
      in all alveolates. By creating fluorescent protein fusion reporters for the
      family members we determined the spatiotemporal patterns of all 14 IMC proteins
      through tachyzoite development. This revealed several distinct distribution
      patterns and some provide the basis for novel structural models such as the
      assembly of certain family members into the basal complex. Furthermore we
      identified IMC15 as an early marker of budding and, lastly, the dynamic patterns
      observed throughout cytokinesis provide a timeline for daughter parasite
      development and division.

PMID- 20698860
TI  - Homocysteine impaired endothelial function through compromised vascular
      endothelial growth factor/Akt/endothelial nitric oxide synthase signalling.
AB  - 1. Hyperhomocysteinaemia (HHcy) is associated with endothelial dysfunction and
      has been recognized as a risk factor of cardiovascular disease. The present study
      aimed to investigate the effect of homocysteine (Hcy) on endothelial function in
      vivo and in vitro, and the underlying signalling pathways. 2. The HHcy animal
      model was established by intragastric administration with l-methionine in rats.
      Plasma Hcy and nitric oxide (NO) concentration were measured by fluorescence
      immunoassay or nitrate reductase method, respectively. Vasorelaxation in response
      to acetylcholine and sodium nitroprusside were carried out on aortic rings. Human
      umbilical vein endothelial cells (HUVEC) were treated with indicated
      concentrations of Hcy in the in vitro experiments. Intracellular NO level and NO
      concentration in culture medium were assayed. The alterations of possible
      signalling proteins were detected by western blot analysis. 3. l-methionine
      administration induced a significant increase in plasma Hcy and decrease in
      plasma NO. Endothelium-dependent relaxation of aortic rings in response to
      acetylcholine was impaired in l-methionine-administrated rats. The in vitro study
      showed that Hcy reduced both intracellular and culture medium NO levels.
      Furthermore, Hcy decreased phosphorylation of endothelial nitric oxide synthase
      (eNOS) at serine-1177 and phosphorylation of Akt at serine-473. Hcy-induced
      dephosphorylation of eNOS at Ser-1177 was partially reversed by insulin (Akt
      activator) and GF109203X (PKC inhibitor). Furthermore, Hcy reduced vascular
      endothelial growth factor (VEGF) expression in a dose-dependent manner. 4. In
      conclusion, Hcy impaired endothelial function through compromised
      VEGF/Akt/endothelial nitric oxide synthase signalling. These findings will be
      beneficial for further understanding the role of Hcy in cardiovascular disease.

PMID- 20698861
TI  - Occupational methacrylate and acrylate allergy--cross-reactions and possible
      screening allergens.
AB  - BACKGROUND: Acrylic resin monomers, especially acrylates and methacrylates, are
      important occupational allergens. AIMS: To analyse patterns of concomitant patch
      test reactions to acrylic monomers in relation to exposure, and to suggest
      possible screening allergens. PATIENTS/METHODS: We reviewed the patch test files
      for the years 1994-2009 at the Finnish Institute of Occupational Health for
      allergic reactions to acrylic monomers, and analysed the clinical records of
      sensitized patients. RESULTS: In a group of 66 patients allergic to an acrylic
      monomer, the most commonly positive allergens were three methacrylates, namely
      ethyleneglycol dimethacrylate (EGDMA), 2-hydroxyethyl methacrylate (2-HEMA) and 2
      hydroxypropyl methacrylate (2-HPMA), and an acrylate, namely diethyleneglycol
      diacrylate (DEGDA). The patterns of concomitant reactions imply that exposure to
      methacrylates may induce cross-reactivity to acrylates, whereas exposure to
      acrylates usually does not lead to cross-allergy to methacrylates. Screening for
      triethyleneglycol diacrylate (TREGDA) in the baseline series was found to be
      useful, as 3 of 8 patients with diagnosed occupational acrylate allergy might
      have been missed without the screening. CONCLUSIONS: A short screening series of
      four allergens, EGDMA, DEGDA, 2-HPMA and pentaerythritol triacrylate (PETA),
      would have screened 93% of our 66 patients; each of the remaining 5 patients
      reacted to different acrylic monomer(s).

PMID- 20698862
TI  - Study of pro- and anti-inflammatory cytokine profile in the patients with
      parthenium dermatitis.
AB  - BACKGROUND: Parthenium dermatitis is a common airborne allergic contact
      dermatitis induced by exposures to the weed Parthenium hysterophorus. The disease
      manifests as itchy erythematous papules, papulovesicular and plaque lesions on
      exposed areas of the body. OBJECTIVES: The aim of this study was to show the
      alterations in pro/anti-inflammatory cytokines in parthenium dermatitis. METHODS:
      The study included 50 patients with parthenium dermatitis confirmed by patch
      testing using aqueous extracts of P. hysterophorus and 50 age-matched healthy
      controls. The levels of pro-inflammatory [tumour necrosis factor-alpha (TNF
      alpha), interleukin (IL)-6, IL-8, and IL-17] and anti-inflammatory (IL-4 and IL
      10) cytokines were estimated by commercially available high sensitivity enzyme
      linked immunosorbent assay (ELISA) kits. RESULTS: All the dermatitis patients
      showed significantly (P < 0.001) elevated levels of TNF-alpha, IL-6, IL-8, and IL
      17 levels as compared to healthy controls. In contrast, the anti-inflammatory
      cytokine IL-4 showed an insignificant decrease (P < 0.217) and a decrease in
      level of IL-10 was statistically significant (0.001) compared with controls.
      CONCLUSIONS: The present study suggests the involvement of pro-inflammatory
      cytokines in the pathogenesis of parthenium dermatitis. A decrease in levels of
      anti-inflammatory cytokines was demonstrated, which could not downregulate pro
      inflammatory cytokines in parthenium dermatitis.

PMID- 20698863
TI  - Chemical matricectomy of nails.

PMID- 20698864
TI  - Dermatologic surgery goes global.

PMID- 20698865
TI  - Commentary on cartilage hinge flap for the repair of antihelical defects.

PMID- 20698866
TI  - Digital block with and without epinephrine during chemical matricectomy with
      phenol.
AB  - BACKGROUND: Digital block with epinephrine is safe in selected patients. Chemical
      matricectomy with phenol is a successful, cheap, and easy method for the
      treatment of ingrown nails. OBJECTIVE: To determine the effect of digital block
      with epinephrine in chemical matricectomy with phenol. MATERIAL AND METHODS:
      Forty-four patients with ingrown toenail were randomly divided into two groups.
      The plain lidocaine group (n=22) underwent digital anesthesia using 2% plain
      lidocaine, and the lidocaine with epinephrine group (n=22) underwent digital
      anesthesia with 2% lidocaine with 1:100,000 epinephrine. In the postoperative
      period, the patients were evaluated for pain, drainage, and peripheral tissue
      destruction and were followed for up to 18 months for recurrence. RESULTS: The
      mean anesthetic volume used in the epinephrine group (2.2 +/- 0.4 mL) was
      significantly lower than the plain lidocaine group (3.1 +/- 0.6 mL). There was no
      statistically significant difference in postoperative pain and recurrence rates,
      but duration of drainage was significantly shorter in the epinephrine group (11.1
      +/- 2.5 days) than in the plain lidocaine group (19.0 +/- 3.8 days). CONCLUSION
      Digital block with epinephrine is safe in selected patients, and epinephrine
      helps to shorten the postoperative drainage period. The authors have indicated no
      significant interest with commercial supporters.

PMID- 20698867
TI  - The nasal sidewall rotation flap: a workhorse flap for small defects of the
      distal nose.
AB  - BACKGROUND: Skin cancers of the nasal tip present a challenge for the
      dermatologic surgeon. The bilobed flap has been widely used as the "workhorse"
      flap for such defects but requires meticulous design and may be complicated by a
      tendency toward pin-cushioning. OBJECTIVE: To describe the use of the nasal
      sidewall rotation (NSR) flap for reconstructing defects on the nasal tip.
      METHODS: A retrospective analysis of the Mohs micrographic surgery database over
      a 4-year period was performed. All cases in which the NSR flap was used were
      identified. Defect location and size and any postoperative complications were
      noted. All patients were reviewed at the time of suture removal and at 6 weeks.
      RESULTS: There were 65 cases (19 men and 46 women). Age ranged from 39 to 86
      (mean 60.5, median 59). Defect size varied from 0.4 to 2.0 cm in diameter, with
      63% measuring 1.0 to 1.4 cm. Good to excellent results were seen in all patients,
      and postoperative complications were uncommon and minor. CONCLUSION The NSR flap
      is a versatile and useful alternative for reconstructing surgical defects of the
      nasal tip. The authors have indicated no significant interest with commercial
      supporters.

PMID- 20698868
TI  - Apples, oranges, and methicillin-resistant Staphylococcus aureus.

PMID- 20698869
TI  - Preoperative methicillin-resistant Staphylococcus aureus screening in Mohs
      surgery appears to decrease postoperative infections.
AB  - BACKGROUND: Colonization with methicillin-resistant Staphylococcus aureus (MRSA)
      places patients at risk for postoperative MRSA wound infections. OBJECTIVE: To
      determine the effect of a decontamination and prophylaxis protocol on
      postoperative MRSA wound infections in patients with nasal MRSA. METHODS &
      MATERIALS: Wound cultures over a 23-month period were reviewed before and 11
      months after implementation of a screening and decontamination protocol. After
      preoperative MRSA screening with nasal swabs, carriers were instructed to use
      intranasal mupirocin for 5 to 7 days before surgery and 5 to 7 days of
      trimethoprim-sulfamethoxazole starting the day before surgery. RESULTS: During
      the 23 months before prescreening evaluation, we performed 3,633 Mohs surgical
      cases, and 12 postoperative MRSA wound infections (0.3%) occurred. Subsequently,
      963 patients underwent screening for MRSA, and 23 MRSA carriers were identified
      (2.4%). Of the 22 who underwent the decontamination and treatment protocol, none
      developed postoperative wound infections. One MRSA carrier did not receive
      preoperative treatment and subsequently developed a MRSA wound infection. There
      were no other MRSA infections. CONCLUSION: Preoperative MRSA screening and
      implementation of a decontamination protocol appears to decrease postoperative
      MRSA wound infections after Mohs surgery. Although an interesting observation,
      controlled studies of clinical and cost effectiveness are required before general
      implementation. The authors have indicated no significant interest with
      commercial supporters.

PMID- 20698870
TI  - Heightened infection-control practices are associated with significantly lower
      infection rates in office-based Mohs surgery.
AB  - BACKGROUND: Reported infection rates for Mohs micrographic surgery (MMS) range
      from less than 1% to 3.5%. OBJECTIVE: To determine whether lower infection rates
      are possible for MMS with a consistently applied infection-control regimen.
      METHODS: A series of 832 consecutive patients with 950 tumors undergoing MMS
      formed the cohort for a retrospective study of infections before and after a
      program of heightened infection-control practices at a single-surgeon academic
      Mohs practice. The sterility upgrade included jewelry restrictions, alcohol hand
      scrub before stages and reconstruction, sterile gloves and (during
      reconstruction) sterile gowns for staff, and sterile towels and dressings for
      patients during Mohs stages. RESULTS: Infection rate was 2.5% (9 infections/365
      tumors) before the sterility upgrade and 0.9% (5 infections/585 tumors) after, a
      statistically significant difference (p=.04). CONCLUSION: MMS already has low
      rates of infection, but this study shows that rigorous infection-control
      practices can significantly affect infection rates. The authors have indicated no
      significant interest with commercial supporters.

PMID- 20698871
TI  - Predictive factors for false negative sentinel lymph node in melanoma patients.
AB  - BACKGROUND: Sentinel lymph node biopsy (SLNB) represents a useful tool for
      staging melanoma patients. However false-negative SLNB are reported in the
      literature. OBJECTIVE: The aim of our study is to identify predictive factors for
      false-negative SLNB in melanoma patients. MATERIALS AND METHODS: We conducted a
      retrospective analysis on 316 melanoma patients who underwent SLNB and were
      followed up at the Department of Dermatology and Plastic Surgery of University of
      Rome "Sapienza" from March 1994 to June 2008. RESULTS: In our patients, SLNB was
      positive in 35 cases (11.07%) whereas it was negative in 281 cases (88.93%);
      12/316 patients (3.8%) had positive SLNB and positive therapeutic lymph node
      dissection (TLND); 23/316 (7.28%) patients had positive SLNB and negative TLND;
      266/316 (84.18%) patients had negative SLNB but without subsequent metastases in
      the SLN site; 15/316 (4.74%) patients had negative SLNB, but with subsequent
      metastases in the same SLN site (false-negative patients). Among the different
      prognostic factors, only ulceration was the main predictive factor for false
      negative SLNB, according to statistical analysis (p=.0420). CONCLUSION: Our data
      confirm that SLNB is a useful technique for staging melanoma patients. However,
      in patients with negative SLNB, a closer follow-up is recommended when ulceration
      is present. The authors have indicated no significant interest with commercial
      supporters.

PMID- 20698872
TI  - Agreement on the clinical diagnosis and management of cutaneous squamous
      neoplasms.
AB  - BACKGROUND: Diagnostic accuracy and preferred therapeutic strategies for actinic
      keratoses (AKs) and squamous cell carcinoma (SCC) have significant public health
      implications. OBJECTIVE: To evaluate clinical-pathologic agreement on the
      diagnosis of AKs and early SCCs and to characterize the effect of diagnosis on
      therapeutic decisions. METHODS & MATERIALS: Nine dermatologists and two
      dermatopathologists reviewed an image-based dataset of AKs and early SCCs.
      Clinical-pathologic agreement, inter- and intraobserver reliability for clinical
      diagnosis, and frequencies of therapies according to pathologic diagnosis were
      assessed. RESULTS: Clinical-pathologic (kappa=0.10) agreement was poor, whereas
      interobserver (kappa=0.24) and intraobserver (kappa=0.28) agreements were fair.
      Participants were more likely to treat AKs with cryotherapy (64.2%) and to manage
      SCCs with surgery (72.8%). Therapeutic choice rarely changed after participants
      were shown histological photomicrographs. Participating clinicians treated most
      lesions histologically diagnosed as SCC in situ arising within AK using surgery,
      whereas pathologists selected cryotherapy or curettage and electrodesiccation for
      these lesions. CONCLUSION: We found poor clinical-pathologic agreement and
      reproducibility for clinically distinguishing between AK and early SCC even
      between skin cancer specialists from a single academic group practice.
      Nomenclature used in the pathologic diagnosis of AK and SCC affects clinicians'
      therapeutic decisions. The authors have indicated no significant interest with
      commercial supporters.

PMID- 20698873
TI  - Effect of physical activity on nonmelanoma skin cancer risk in kidney, liver, and
      pancreatic transplant patients.
AB  - BACKGROUND: Physical activity has been associated with a lower risk of cancer,
      including melanoma, but the effect has not yet been assessed for nonmelanoma skin
      cancer (NMSC). OBJECTIVE: To determine whether the risk of skin cancer differs
      according to physical activity level in patients at high risk for NMSC. METHODS:
      We conducted a retrospective cohort study in kidney, liver, and pancreatic
      transplant patients via telephone interview. Physical activity scores were
      calculated for each patient using a previously validated questionnaire. Sun
      exposure history and skin type were also recorded. The outcome of interest was a
      biopsy-proven diagnosis of at least one NMSC. RESULTS: Of 142 subjects, 45 (32%)
      developed NMSC. There was no significant effect of physical activity on the
      development of NMSC. CONCLUSIONS: Physical activity level may not be a major
      predictor of skin cancer risk in organ transplant patients. Controlled trials and
      population-based studies are needed to determine whether exercise can decrease
      the risk of NMSC in the general population. The authors have indicated no
      significant interest with commercial supporters.

PMID- 20698874
TI  - Fractional resurfacing: a step in progress.

PMID- 20698875
TI  - Review of the literature: Treatment of dyspigmentation with fractionated
      resurfacing.
AB  - BACKGROUND: Traditional ablative laser resurfacing is associated with adverse
      side effects, including prolonged erythema, edema, burning, milia, acne,
      crusting, and hypo- and hyperpigmentation. Fractional photothermolysis (FP) has
      been introduced to overcome the disadvantages of traditional ablative and
      nonablative resurfacing. With FP, the microscopic, pixilated pattern of wounding
      in the dermis results in significant skin pigmentary and textural improvements
      without the adverse effects of prolonged wound healing and risks of
      dyspigmentation associated with traditional ablative resurfacing. FP has been
      reported to improve hypo- and hyperpigmentation in a variety of cutaneous
      conditions. OBJECTIVE: To review the dermatologic literature on the use of FP for
      treatment of dyspigmentation. RESULTS: Review of the Medline literature
      identified 35 studies on treatment of cutaneous conditions associated with
      dyspigmentation with ablative FP (AFP) and nonablative FP (NAFP). Specifically,
      we found treatment of melasma, postinflammatory hyperpigmentation, nevus of Ota,
      hypo- and hyperpigmented scars, poikiloderma of Civatte, laser-induced hypo- and
      hyperpigmentation, and dyschromia associated with photoaging. CONCLUSIONS: AFP
      and NAFP are potentially effective modalities for the treatment of
      dyspigmentation of the face and neck. The authors have indicated no significant
      interest with commercial supporters.

PMID- 20698876
TI  - Interneuron subtype specific activation of mGluR1/5 during epileptiform activity
      in hippocampus.
AB  - PURPOSE: Specific inhibitory interneurons in area CA1 of the hippocampus, notably
      those located in stratum oriens-alveus (O/A-INs), are selectively vulnerable in
      patients and animal models of temporal lobe epilepsy (TLE). The excitotoxic
      mechanisms underlying the selective vulnerability of interneurons have not been
      identified but could involve group I metabotropic glutamate receptor subtypes
      (mGluR1/5), which have generally proconvulsive actions and activate prominent
      cationic currents and calcium responses specifically in O/A-INs. METHODS: In this
      study, we examine the role of mGluR1/5 in interneurons during epileptiform
      activity using whole-cell recordings from CA1 O/A-INs and selective antagonists
      of mGluR1alpha (LY367385) and mGluR5 (MPEP) in a disinhibited rat hippocampal
      slice model of epileptiform activity. RESULTS: Our data indicate more prominent
      epileptiform burst discharges and paroxysmal depolarizations (PDs) in O/A-INs
      than in interneurons located at the border of strata radiatum and
      lacunosum/moleculare (R/LM-INs). In addition, mGluR1 and mGluR5 significantly
      contributed to epileptiform responses in O/A-INs but not in R/LM-INs.
      Epileptiform burst discharges in O/A-INs were partly dependent on mGluR5. PDs and
      associated postsynaptic currents were dependent on both mGluR1alpha and mGluR5.
      These receptors contributed differently to postsynaptic currents underlying PDs,
      with mGluR5 contributing to the fast and slow components and mGluR1alpha to the
      slow component. DISCUSSION: These findings support interneuron subtype-specific
      activation and differential contributions of mGluR1alpha and mGluR5 to
      epileptiform activity in O/A-INs, which could be important for their selective
      vulnerability in TLE.

PMID- 20698877
TI  - Published articles should not be dead and buried: introducing research updates.

PMID- 20698879
TI  - Risk factors for pulmonary hypertension in patients with thalassemia intermedia.

PMID- 20698880
TI  - Effects of sangre de drago in an in vitro model of cutaneous neurogenic
      inflammation.
AB  - Sangre de drago (SD) is a viscous bright red resin collected from Croton lechleri
      trees that grow in the South American jungle. This sap is used extensively in the
      native pharmacopoeia to treat skin disorders. Its effectiveness as an inhibitor
      of neurogenic inflammation has been recently demonstrated. To understand the
      underlying mechanisms of these effects, we examined the ability of SD to reduce
      substance P (SP) release in an in vitro model of cutaneous neurogenic
      inflammation (CNI). This model is based on an enzyme immunoassay of SP (an
      inducer of CNI) in a porcine co-culture of dorsal root ganglion neurons and
      keratinocytes. After incubation with different concentrations of SD, we noted an
      immediate and significant dose-dependent decrease in basal SP release, with
      average values of 32% at 1% SD (v/v) and 26% at 0.1% (v/v). On the other hand,
      pretreatment (72 or 1 h) of the co-culture with 1% SD (v/v) was sufficient to
      induce a 111% (72 h) or 65% (1 h) inhibition of capsaicin-induced SP release,
      while 0.1% SD (v/v) triggered a 109% (72 h) or 30% (1 h) inhibition. We conclude
      that sangre de drago is a potent inhibitor of CNI through direct inhibition of
      neuropeptide release by sensory afferent nerves.

PMID- 20698881
TI  - Hidradenitis suppurativa (or Acne inversa) with autosomal dominant inheritance is
      not linked to chromosome 1p21.1-1q25.3 region.
AB  - Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition
      characterized by swollen, painful, inflamed lesions in the axillae, groin,
      armpits and other parts of the body that contain apocrine glands. The aetiology
      of HS is unknown, and earlier reports indicate genetic locus responsible for this
      phenotype on chromosome 1p21.1-1q25.3, but no causative gene(s) have yet been
      identified. We studied two large multigeneration pedigrees (UR251 and UR252), in
      which the condition appeared to segregate as an autosomal dominant trait with
      100% penetrance. No skipping of generations was observed in either family.
      Pedigrees consist of 96 individuals, including 25 affected individuals. Because
      of squamous cell carcinoma, a few deaths were reported in family UR0251. The
      locus on chromosome 1p21.1-1p25.3, known from previous studies is associated with
      HS, was excluded in both families by linkage and haplotype analyses. Further
      studies are in progress to identify the region that is associated with the
      phenotype in these families.

PMID- 20698882
TI  - The expression of microRNA-203 during human skin morphogenesis.
AB  - MicroRNAs are small, non-coding RNAs that regulate gene expression post
      transcriptionally and play important roles in various biological processes. We
      previously identified miR-203 as a skin- and keratinocyte-specific microRNA.
      Moreover, miR-203 has been implicated in repressing 'stemness' in epidermal
      progenitors. Here, we investigate the expression of miR-203 and two of its
      targets, p63 and suppressor of cytokine signalling-3, during human skin
      morphogenesis. MiR-203 in situ hybridization was performed on sections of human
      foetal skin ranging from 14 to 22 weeks' gestation and adult skin. MiR-203 was
      barely detectable at 14 weeks. Its expression became prominent from week 17 and
      was most pronounced in the suprabasal layers of the epidermis, while p63 and SOCS
      3 were preferentially expressed in the basal layer. Differentiation markers such
      as involucrin and filaggrin were expressed mainly in the suprabasal layers of
      epidermis, similar to miR-203. Our results support the involvement of miR-203 in
      skin morphogenesis.

PMID- 20698883
TI  - MicroRNA-23a promotes the growth of gastric adenocarcinoma cell line MGC803 and
      downregulates interleukin-6 receptor.
AB  - MicroRNAs are an evolutionarily conserved class of endogenous noncoding RNAs that
      modulate gene expression at the post-transcriptional level. Recently, microRNA
      23a (miR-23a) has been found to function as a growth-promoting and antiapoptotic
      factor in hepatocellular carcinoma cells. Our previous study showed that miR-23a
      was significantly upregulated in gastric adenocarcinoma tissues. In this study,
      we found that miR-23a promoted the proliferative potential of gastric
      adenocarcinoma cell line MGC803. We also identified IL6R as a direct target gene
      for miR-23a using a fluorescent reporter assay. The mRNA and protein levels of
      IL6R were both inversely correlated with the miR-23a expression level. Our
      results demonstrate that miR-23a can target IL6R and promote the growth activity
      of gastric adenocarcinoma cells in vitro. The downregulation of IL6R by miR-23a
      may explain why the suppression of miR-23a can inhibit gastric cancer cell
      proliferation.

PMID- 20698884
TI  - The perspectives of the application of phage therapy in chronic bacterial
      prostatitis.
AB  - Chronic bacterial prostatitis (CBP) is a long-lasting and crippling disease that
      strongly impacts the patient's quality of life. The diagnosis of CBP is difficult
      and the treatment regimens are not always successful. Poor penetration of
      antibiotics to the prostate tissue, the drug resistance of uropathogens, the
      adverse events associated with antibiotic treatment, the persistence of prostatic
      calculi, and biofilm formation in the prostate gland are factors that contribute
      toward decreasing the cure rate of CBP. The phenomenon of increasing antibiotic
      resistance, which has also been called a clinical super-challenge, has revived
      interest in therapy using bacterial viruses (bacteriophages or phages). Because
      of their mechanism of action, which is completely different from those of all
      antibiotics, phages are effective even against multidrug-resistant bacteria.
      Here, we describe the current perspectives on the possible application of phage
      therapy (PT) in treating CBP. The advantages of therapeutic phages, including
      their interactions with bacterial biofilm, as well as the safety of PT are
      discussed.

PMID- 20698885
TI  - Insights into the dynamics of bacterial communities during chalcopyrite
      bioleaching.
AB  - The microbial ecology of the bioleaching of chalcopyrite ores is poorly
      understood and little effort has been made to handle the microbiological
      components of these processes. In this study, the composition and structure of
      microbial communities in acid mineral bioleaching systems have been studied using
      a PCR-based cloning approach. Denaturing gradient gel electrophoresis (DGGE)
      analysis of PCR-amplified 16S rRNA gene fragments from bacteria was used to
      evaluate the changes in the bacterial community in the process of chalcopyrite
      bioleaching in a shaken flask system. The results revealed that the bacterial
      community was disturbed after the addition of chalcopyrite. Phylogenetic analyses
      of 16S rRNA gene fragments revealed that the retrieved sequences clustered
      together with the genera Acidithiobacillus, Leptospirillum, and Acidovorax.
      Multidimensional scaling analysis of DGGE banding patterns revealed that the
      process of chalcopyrite bioleaching in 46 days was divided into four stages. In
      the first stage, Leptospirillum were dominant. In the second stage,
      Leptospirillum and Acidithiobacillus groups were mainly detected. In the third
      and fourth stages, the bacterial community was relatively stable and was
      dominated by Leptospirillum and Acidithiobacillus. These results extend our
      knowledge on the microbial dynamics in chalcopyrite bioleaching, a key issue
      required to improve commercial applications.

PMID- 20698886
TI  - Bacterial diversity on the surface of potato tubers in soil and the influence of
      the plant genotype.
AB  - The surface of tubers might be a reservoir for bacteria that are disseminated
      with seed potatoes or that affect postharvest damage. The numbers of culturable
      bacteria and their antagonistic potential, as well as bacterial community
      fingerprints were analysed from tubers of seven field-grown potato genotypes,
      including two lines with tuber-accumulated zeaxanthin. The plant genotype
      significantly affected the number of culturable bacteria only at one field site.
      Zeaxanthin had no effect on the bacterial plate counts. In dual culture, 72 of
      700 bacterial isolates inhibited at least one of the potato pathogens Rhizoctonia
      solani, Verticillium dahliae or Phytophthora infestans, 12 of them suppressing
      all three. Most of these antagonists were identified as Bacillus or Streptomyces.
      From tubers of two plant genotypes, including one zeaxanthin line, higher numbers
      of antagonists were isolated. Most antagonists showed glucanase, cellulase and
      protease activity, which could represent mechanisms for pathogen suppression. PCR
      DGGE fingerprints of the 16S rRNA genes of bacterial communities from the tuber
      surfaces revealed that the potato genotype significantly affected the Pseudomonas
      community structure at one site. However, the genotypes showed nearly identical
      fingerprints for Bacteria, Actinobacteria, Alphaproteobacteria,
      Betaproteobacteria, Bacillus and Streptomycetaceae. In conclusion, tuber
      associated bacteria were only weakly affected by the plant genotype.

PMID- 20698888
TI  - Comparison of the MTT1- and MAL31-like maltose transporter genes in lager yeast
      strains.
AB  - Maltose transporter genes were isolated from four lager yeast strains and
      sequenced. All four strains contain at least two different types of maltose
      transporter genes, MTT1 and MAL31. In addition, 'long' 2.7 kb, and 'short' 2.4
      kb, versions of each type exist. The size difference is caused by the insertion
      of two repeats of 147 bp into the promoter regions of the long versions of the
      genes. As a consequence of the insertion, two Mal63-binding sites move 294 bp
      away from the transcription initiation site. The 2.4- and 2.7-kb versions are
      further highly similar. Only the 2.4-kb versions and not the 2.7-kb versions of
      MTT1 could restore the rapid growth of lager yeast strain A15 on maltotriose in
      the presence of antimycin A. These results suggest that insertion of the two
      repeats into the promoter region of the 'long versions' of MTT1 genes led to a
      diminished expression of these genes. None of the tested long and short versions
      of the MAL31 genes were able to restore this growth. As the promoter regions of
      the MTT1 and MAL31 genes are identical, small differences in the protein sequence
      may be responsible for the different properties of these genes.

PMID- 20698890
TI  - Surrogate endpoints in randomized cardiovascular clinical trials.
AB  - Surrogate endpoints predict the occurrence and timing of a clinical endpoint of
      interest (CEI). Substitution of a surrogate endpoint for a CEI can dramatically
      reduce the time and cost necessary to complete a Phase III clinical trial.
      However, assurance that use of a surrogate endpoint will result in a correct
      conclusion regarding treatment effect on a CEI requires prior rigorous validation
      of the surrogate. Surrogate endpoints can also be of substantial use in Phase I
      and II studies to assess whether the intended therapeutic pathway is operative,
      thus providing assurance regarding the reasonableness of proceeding to a Phase
      III trial. This paper discusses the uses and validation of surrogate endpoints.

PMID- 20698891
TI  - Strategy for clinical evaluation and screening of sudden cardiac death relatives.
AB  - Sudden cardiac death (SCD) may be the first and final manifestation of several
      heart diseases. In the young, SCD is often caused by a hereditary cardiac
      disease. As the most frequently seen inherited cardiac diseases have an autosomal
      dominant pattern of inheritance, half of the first-degree relatives are at risk
      of having or developing the same disease. Therefore, screening of these high-risk
      relatives is a rational approach to reduce the incidence of SCD. To offer family
      screening and counseling, the cause of death should be carefully established.
      Autopsy is only performed in a limited number of cases. We advocate for
      systematic autopsies in SCD, because positive findings are crucial for choosing
      the optimal screening program for the relatives. A negative autopsy makes
      identification of at-risk population difficult. However, this finding also
      provides clues to the cardiologist, because a limited number of inherited cardiac
      diseases associated with SCD are without any structural changes. In other cases,
      the autopsy may reveal noncardiac causes of death, which is also important for
      reassuring the relatives. However, in cases with no autopsy or negative findings,
      thorough clinical examinations and selective genetic screening of relatives may
      identify a likely diagnosis in more than 50% of affected families. There is a
      need for consensus regarding routine evaluation of SCD cases and the ethical and
      legal framework related to postmortem testing. We propose an algorithm that
      narrows the diagnostic possibilities in apparently healthy relatives of young SCD
      victims. Molecular autopsy may play an important role.

PMID- 20698892
TI  - Smoking and health: association between telomere length and factors impacting on
      human disease, quality of life and life span in a large population-based cohort
      under the effect of smoking duration.
AB  - Reactive oxygen species (ROS) are of primary importance as they cause damage to
      lipids, proteins, and DNA either endogenously by cellular mechanism, or through
      exogenous exposure to environmental injury factors, including oxidation insult
      factors, such as tobacco smoke. Currently 46.3 million adults (25.7 percent of
      the population) are smokers. This includes 24 million men (28.1 percent of the
      total) and more than 22 million women (23.5 percent). The prevalence is highest
      among persons 25-44 years of age. Cigarette smokers have a higher risk of
      developing several chronic disorders. These include fatty buildups in arteries,
      several types of cancer and chronic obstructive pulmonary disease (lung
      problems). As peripheral leukocytes have been the main target of human telomere
      research, most of what is known about human telomere dynamics in vivo is based on
      these cells. Leukocyte telomere length (TL) is a complex trait that is shaped by
      genetic, epigenetic, and environmental determinants. In this article, we consider
      that smoking modifies leukocyte TL in humans and contributes to its variability
      among individuals, although the smoking effect on TL and its relation with other
      metabolic indices may accelerate biological aging and development of smoking
      induced chronic diseases in a large human population-based cohorts with smoking
      behavior. Recent studies confirmed that individuals with shorter telomeres
      present a higher prevalence of arterial lesions and higher risk of cardiovascular
      disease mortality. This study originally suggests that efficient therapeutic
      protection of TL and structure in response to stresses that are known to reduce
      TL, such as oxidative damage or inflammation associated with tobacco smoking,
      would lead to better telomere maintenance. Recently, we have discovered the
      potential use of telomere-restorative imidazole-containing dipeptide (non
      hydrolized carnosine, carcinine) based therapy for better survival of smokers. We
      conclude that a better therapeutic or nutritional maintenance of TL may confer
      healthy aging in smokers and exceptional longevity in regularly ROS-exposed human
      survivors.

PMID- 20698893
TI  - Septate-tubular textures in 2.0-Ga pillow lavas from the Pechenga Greenstone
      Belt: a nano-spectroscopic approach to investigate their biogenicity.
AB  - Pillow lava rims and interpillow hyaloclastites from the upper part of the
      Pechenga Greenstone Belt, Kola Peninsula, N-Russia contain rare tubular textures
      15-20 MUm in diameter and up to several hundred MUm long in prehnite-pumpellyite
      to lower greenschist facies meta-volcanic glass. The textures are septate with
      regular compartments 5-20 MUm across and exhibit branching, stopping and no
      intersecting features. Synchrotron micro-energy dispersive X-ray was used to
      image elemental distributions; scanning transmission X-ray microscopy, Fe L-edge
      and C K-edge were used to identify iron and carbon speciation at interfaces
      between the tubular textures and the host rock. In situ U-Pb radiometric dating
      by LA-MC-ICP-MS (laser ablation multicollector inductively coupled plasma mass
      spectrometry) of titanite from pillow lavas yielded a metamorphic age of 1790 +/-
      89 Ma. Focused ion-beam milling combined with transmission electron microscopy
      was used to analyze the textures in three dimensions. Electron diffraction showed
      that the textures are mineralized by orientated pumpellyite. On the margins of
      the tubes, an interface between mica or chlorite and the pumpellyite shows
      evidence of dissolution reactions where the pumpellyite is replaced by
      mica/chlorite. A thin poorly crystalline Fe-phase, probably precipitated out of
      solution, occurs at the interface between pumpellyite and mica/chlorite. This
      sequence of phases leads to the hypothesis that the tubes were initially hollow,
      compartmentalized structures in volcanic glass that were mineralized by
      pumpellyite during low-grade metamorphism. Later, a Fe-bearing fluid mineralized
      the compartments between the pumpellyite and lastly the pumpellyite was partially
      dissolved and replaced by chlorite during greenschist metamorphism. The most
      plausible origin for a septate-tubular texture is a progressive etching of the
      host matrix by several generations of microbes and subsequently these tubes were
      filled by authigenic mineral precipitates. This preserves the textures in the
      rock record over geological time. The micro textures reported here thus represent
      a pumpellyite-mineralized trace fossil that records a Paleoproterozoic sub
      seafloor biosphere.

PMID- 20698896
TI  - Consumers' use of HCAHPS ratings and word-of-mouth in hospital choice.
AB  - OBJECTIVE: To investigate the impact of the HCAHPS report of patient experiences
      and word-of-mouth narratives on consumers' hospital choice. DATA SOURCES: Online
      consumer research panel of U.S. adults ages 18 and older. STUDY DESIGN/DATA
      COLLECTION/EXTRACTION METHODS: In an experiment, 309 consumers were randomly
      assigned to see positive or negative information about a hospital in two
      modalities: HCAHPS graphs and a relative's narrative e-mail. Then they indicated
      their intentions to choose the hospital for elective surgery. PRINCIPAL FINDINGS:
      A simple, one-paragraph e-mail and 10 HCAHPS graphs had similar impacts on
      consumers' hospital choice. When information was inconsistent between the HCAHPS
      data and e-mail narrative, one modality attenuated the other's effect on hospital
      choice. CONCLUSIONS: The findings illustrate the power of anecdotal narratives,
      suggesting that policy makers should consider how HCAHPS data can be affected by
      word-of-mouth communication.

PMID- 20698897
TI  - Total quality management and performance in substance abuse treatment centers.
AB  - OBJECTIVE: To examine the relationship of organizational characteristics of
      substance abuse treatment centers with their use of quality management practices
      (total quality management [TQM]) and the contribution of TQM use to a center's
      provision of comprehensive care and to use of evidence-based treatment practices.
      DATA SOURCES: Data were collected from a national sample of over 700 private and
      public substance abuse treatment centers in the National Treatment Center Study.
      STUDY DESIGN: The design was a cross-sectional field study. The key variables
      were three TQM practices, the provision of comprehensive treatment services, and
      the implementation of evidence-based treatment practices. Numerous organizational
      characteristics were controlled. DATA COLLECTION: The data were obtained through
      interviews with administrative directors and clinical directors of the treatment
      centers in 2002-2004. PRINCIPAL FINDINGS: In multivariate models, TQM practices
      were positively related to provision of comprehensive care and use of evidence
      based practices. A limited set of organizational characteristics predicted the
      use of TQM practices. CONCLUSIONS: Substance abuse treatment centers'
      implementation of TQM processes may be positively related to the quality and cost
      effectiveness of care provided.

PMID- 20698898
TI  - What is the experience of national quality campaigns? Views from the field.
AB  - OBJECTIVE: To identify key characteristics of a national quality campaign that
      participants viewed as effective, to understand mechanisms by which the campaign
      influenced hospital practices, and to elucidate contextual factors that modified
      the perceived influence of the campaign on hospital improvements. DATA SOURCES:
      In-depth interviews, hospital surveys, and Health Quality Alliance data. STUDY
      DESIGN: We conducted a qualitative study using in-depth interviews with clinical
      and administrative staff (N = 99) at hospitals reporting strong influence (n = 6)
      as well as hospitals reporting limited influence (n = 6) of the Door-to-Balloon
      (D2B) Alliance, a national quality campaign to improve heart attack care. We
      analyzed these qualitative data as well as changes in hospital use of recommended
      strategies reported through a hospital survey and changes in treatment times
      using Health Quality Alliance data. DATA COLLECTION METHODS: In-depth, open-ended
      interviews; hospital survey. PRINCIPAL FINDINGS: Key characteristics of the
      national quality campaign viewed as enhancing its effectiveness were as follows:
      credibility of the recommendations, perceived simplicity of the recommendations,
      alignment with hospitals' strategic goals, practical implementation tools, and
      breadth of the network of peer hospitals in the D2B Alliance. Perceived
      mechanisms of the campaign's influence included raising awareness and influencing
      goals, fostering strategy adoption, and influencing aspects of organizational
      culture. Modifying contextual factors included perceptions about current
      performance and internal championship for the recommended changes. CONCLUSIONS:
      The impact of national quality campaigns may depend on both campaign design
      features and on the internal environment of participating hospitals.

PMID- 20698899
TI  - Medicare payments for common inpatient procedures: implications for episode-based
      payment bundling.
AB  - BACKGROUND: Aiming to align provider incentives toward improving quality and
      efficiency, the Center for Medicare and Medicaid Services is considering broader
      bundling of hospital and physician payments around episodes of inpatient surgery.
      Decisions about bundled payments would benefit from better information about how
      payments are currently distributed among providers of different perioperative
      services and how payments vary across hospitals. STUDY DESIGN: Using the national
      Medicare database, we identified patients undergoing one of four inpatient
      procedures in 2005 (coronary artery bypass [CABG], hip fracture repair, back
      surgery, and colectomy). For each procedure, price-standardized Medicare payments
      from the date of admission for the index procedure to 30 days postdischarge were
      assessed and categorized by payment type (hospital, physician, and postacute
      care) and subtype. RESULTS: Average total payments for inpatient surgery episodes
      varied from U.S.$26,515 for back surgery to U.S.$45,358 for CABG. Hospital
      payments accounted for the largest share of total payments (60-80 percent,
      depending on procedure), followed by physician payments (13-19 percent) and
      postacute care (7-27 percent). Overall episode payments for hospitals in the
      lowest and highest payment quartiles differed by U.S.$16,668 for CABG,
      U.S.$18,762 for back surgery, U.S.$10,615 for hip fracture repair, and
      U.S.$12,988 for colectomy. Payments to hospitals accounted for the largest share
      of variation in payments. Among specific types of payments, those associated with
      30-day readmissions and postacute care varied most substantially across
      hospitals. CONCLUSIONS: Fully bundled payments for inpatient surgical episodes
      would need to be dispersed among many different types of providers. Hospital
      payments--both overall and for specific services--vary considerably and might be
      reduced by incentives for hospitals and physicians to improve quality and
      efficiency.

PMID- 20698900
TI  - Pyrosequencing and characterization of immune response genes from the American
      dog tick, Dermacentor variabilis (L.).
AB  - Ticks continue to be a threat to animal and human health, and new and novel
      control strategies are needed for ticks and tick-borne pathogens. The
      characterization of the tick-pathogen interface and the tick immune response to
      microbial infections is fundamental toward the formulation of new control
      strategies for ticks and the pathogens they transmit. Our overall hypothesis for
      this research is that the tick immune system manages the maintenance of
      pathogens. Therefore, discovery of tick immune response genes may provide targets
      for novel control strategies directed toward reducing vector competency and
      pathogen transmission. In these studies, 454 pyrosequencing, a high-throughput
      genomic sequencing method was used to discover tick genes expressed in response
      to bacterial and fungal infections. Expressed sequence tags (ESTs) were analysed
      from Dermacentor variabilis ticks that had been injected with bacteria
      (Escherichia coli, Bacillus subtilis, Micrococcus luteus) or fungi (Saccharomyces
      cerevisiae and Candida albicans) and ticks that were naturally infected with the
      intracellular bacterium, Anaplasma marginale. By this approach, ESTs were
      assembled into 5995 contigs. Contigs fell into the five main functional
      categories of metabolism, genetic information processing, environmental
      information processing, cellular processes and human diseases. We identified more
      than 30 genes that are likely to encode for proteins involved in tick immune
      function. We further analysed by reverse transcriptase PCR (RT-PCR) the
      expression of 22 of these genes in each of our bacterial or fungal treatment
      groups and found that seven were up-regulated. Up-regulation of these seven genes
      was confirmed for bacterial, but not fungal treatment by quantitative PCR (qPCR).
      One of these products was novel, encoding a new tick defensin. Our results
      clearly demonstrate the complexities of the tick immune system and mark new
      directions for further study and characterization of proteins that modulate
      microbial infections in the American dog tick.

PMID- 20698901
TI  - Molecular cloning, transcriptional regulation, and differential expression
      profiling of vitellogenin in two wing-morphs of the brown planthopper,
      Nilaparvata lugens Stal (Hemiptera: Delphacidae).
AB  - The brown planthopper, Nilaparvata lugens, is a serious pest of rice crops
      throughout Asia and exhibits wing dimorphism, with brachypterous adults having
      reduced wings and macropterous adults possessing fully developed wings. To
      understand the reproductive strategies in two wing-morphs of this insect, the
      transcript encoding the major yolk protein precursor, vitellogenin (Vg), was
      cloned. The complete mRNA transcript was 6314 bp, which encodes a protein of 2063
      residues including an 18-residue putative signal peptide. Analysis of the mature
      protein revealed two vitellogenin-N (or lipoprotein amino-terminal) domains near
      the N-terminus and a von Willebrand factor type D domain near the C-terminus. In
      addition, a highly conserved motif GL/ICG, and a number of cysteine residues were
      identified near the C-terminus. Northern blot analysis identified a ~6.8 kb Vg
      gene transcript that was expressed exclusively in the adult female fat body
      cells. The expression profile revealed that the Vg gene starts to be expressed
      earlier (on day 3) in brachypters as compared to macropters where the mRNA
      transcript was observed on day 4. However, in both morphs, the amount of Vg mRNA
      increased to reach high levels during vitellogenic periods [from day 4 (in
      brachypters) and day 5 (in macropters) and onwards]. Reflecting the RNA
      transcription pattern, the Vg signal was detected by immunoblotting on day 3 and
      day 4 in haemolymph of brachypterous and macropterous females, respectively, and
      that was increased every day and remained high during the vitellogenic periods.
      Furthermore, the topical application of juvenile hormone (JH) III had up
      regulated the Vg gene expression suggesting that the Vg gene is regulated by JH
      in N. lugens. In addition, it was demonstrated by Southern blot analysis that
      there exists a single copy of the gene in the N. lugens genome. A delayed trend
      in expression (of both the transcript and the protein) demonstrated by
      macropterous females in the present studies supports the hypothesis of
      prereproductive long distance migration in this wing-dimorphic species.

PMID- 20698902
TI  - Complementary and alternative medicine use in England: results from a national
      survey.
AB  - OBJECTIVES: In many countries, recent data on the use of complementary and
      alternative medicine (CAM) are available. However, in England, there is a paucity
      of such data. We sought to determine the prevalence and predictors of CAM use in
      England. DESIGN: Data were obtained from the Health Survey for England 2005, a
      national household survey that included questions on CAM use. We used binary
      logistic regression modelling to explore whether demographic, health and
      lifestyle factors predict CAM use. RESULTS: Data were available for 7630
      respondents (household response rate 71%). Lifetime and 12-month prevalence of
      CAM use were 44.0% and 26.3% respectively; 12.1% had consulted a practitioner in
      the preceding 12 months. Massage, aromatherapy and acupuncture were the most
      commonly used therapies. Twenty-nine percent of respondents taking prescription
      drugs had used CAM in the last 12 months. Women (OR 0.491, 95% CI: 0.419, 0.577),
      university educated respondents (OR 1.296, 95% CI: 1.088, 1.544), those suffering
      from anxiety or depression (OR 1.341, 95% CI: 1.074, 1.674), people with poorer
      mental health (on GHQ: OR 1.062, 95% CI 1.026, 1.100) and lower levels of
      perceived social support (1.047, 95% CI: 1.008, 1.088), people consuming >= 5
      portions of fruit and vegetables a day (OR 1.327, 95% CI: 1.124, 1.567) were
      significantly more likely to use CAM. CONCLUSION: Complementary and alternative
      medicine use in England remains substantial, even amongst those taking
      prescription drugs. These data serve as a valuable reminder to medical
      practitioners to ask patients about CAM use and should be routinely collected to
      facilitate prioritisation of the research agenda in CAM.

PMID- 20698909
TI  - Temporal expression of calcium/calmodulin-dependent adenylyl cyclase isoforms in
      rat articular chondrocytes: RT-PCR and immunohistochemical localization.
AB  - A multitude of signalling cascades are implicated in the homeostasis of articular
      chondrocytes. However, the identity of these signalling pathways is not fully
      established. The 3, 5'-cyclic AMP-mediated signalling system is considered to be
      a prototype. Adenylyl cyclase (AC) is an effector enzyme responsible for the
      synthesis of cAMP. There are 10 mammalian AC isoforms and some of these are
      differentially regulated by calcium/calmodulin (Ca2(+) /CaM). Ca2(+) is known to
      play an important role in the development and maintenance of skeletal tissues.
      Ca2(+) /CaM-dependent AC isoforms and their temporal expression in articular
      chondrocytes in rats were identified using RT-PCR and immunohistochemistry
      techniques. All Ca2(+) /CaM-dependent AC isoforms were expressed in chondrocytes
      from all age groups examined. Each isoform was differentially expressed in
      developing and adult articular chondrocytes. Generally, expression of AC isoforms
      was observed to increase with age, but the increase was not uniform for all
      Ca2(+) /CaM-dependent AC isoforms. Expression of Ca2(+) /CaM-dependent AC
      isoforms along with other signalling molecules known to be present in articular
      chondrocytes indicate complicated and multifactorial signalling cascades involved
      in the development and homeostasis of articular cartilage. The significance of
      these findings in terms of articular chondrocyte physiology is discussed.

PMID- 20698910
TI  - Assessment of adenovirus, hepatitis A virus and rotavirus presence in
      environmental samples in Florianopolis, South Brazil.
AB  - AIMS: To assess the presence of human adenovirus (HAdV), hepatitis A (HAV) virus
      and rotavirus A (RV-A) in environmental samples from the Southern region of
      Brazil and to provide viral contamination data for further epidemiological
      studies and governmental actions. METHODS AND RESULTS: Water samples from various
      sources (seawater, lagoon brackish water, urban wastewater, drinking water
      sources-with and without chlorination and water derived from a polluted creek)
      and oysters of two growing areas were analysed by enzymatic amplification (nested
      PCR and RT-PCR), quantification of HAdV genome (qPCR) and viral viability assay
      by integrated cell culture-PCR (ICC-PCR). From June 2007 to May 2008 in a total
      of 84 water samples, 54 (64.2%) were positive for HAdV, 16 (19%) for RV-A and 7
      (8.3%) for HAV. Viability assays showed nonpositive samples for HAV; though,
      infectious viruses were confirmed for RV-A (12.5%) and HAdV (88.8%). Oyster
      samples by PCR were positive for HAdV (87.5%) and RV-A (8.3%), but none for HAV.
      Quantitative PCR in oysters showed means loads in genomic copies (gc) of 9.1 *
      10(4)  gc g(-1) (oyster farm south) and 1.5 * 10(5)  gc g(-1) (oyster farm north)
      and in waters ranging from 2.16 * 10(6) (lagoon water) to 1.33 * 10(7)  gc l(-1)
      (untreated drinking water). CONCLUSIONS:  This study has shown a widespread
      distribution of the analysed viruses in this particular region with high loads of
      HAdV in the environment which suggests the relevance of evaluating these viruses
      as positive indicators of viral contamination of water. SIGNIFICANCE AND IMPACT
      OF THE STUDY:  The environmental approach in this study provides data concerning
      the prevalence, viability and quantification of enteric viruses in environmental
      waters and oysters in the South region of Brazil and has indicated that their
      presence might pose a risk to population in contact with the environmental
      samples searched.

PMID- 20698911
TI  - Immunoproteomic analysis and identification of novel immunogenic proteins from
      Vibrio harveyi.
AB  - AIMS: The main aim of this study was to screen novel immunogenic proteins of
      Vibrio harveyi, which could be vaccine candidates. METHODS AND RESULTS:   Whole
      cell proteins of V. harveyi, strain Li01 and Huang01, were first separated by
      isoelectric focusing, followed by 2D-PAGE, respectively. Immunogenic proteins
      were identified by Western blotting, using Epinephelus coioides antisera against
      V. harveyi strain Li01. Western blot analyses revealed 16 shared immunogenic
      protein spots in both strains. All of the immunogenic proteins were successfully
      identified and corresponded to 15 proteins. None of these proteins have been
      previously reported as immunogenic for V. harveyi. Of the 15 proteins, 11 are
      specific immunoreactive proteins and four are nonspecific immunoreactive
      proteins. Furthermore, outer membrane protein N (spot 2) and oligopeptide ATP
      binding cassette (ABC) transporter (spot 3) were used as immunogens to immunize
      E. coioides for investigation of their protective abilities and activities. The
      E. coioides immunized with OmpN has abilities to fight against infections caused
      by V. harveyi Li01 and Huang01. However, vaccination with oligopeptide ABC
      transporter induces low protective immune response in fish. CONCLUSIONS:   Eleven
      novel specific antigens were found, and OmpN could potentially be used as vaccine
      candidate for the development of novel vaccine against V. harveyi. SIGNIFICANCE
      AND IMPACT OF THE STUDY: These data show that immunoproteomics methods can be
      successfully applied in identifying immunogenic proteins of V. harveyi, which
      helps to search for the protective antigens in future.

PMID- 20698912
TI  - Proceeding with caution--the importance of negative findings in the science of
      psychopathology.

PMID- 20698913
TI  - Immunohistochemical expression of matrix metalloproteinases in the granulomatous
      rosacea compared with the non-granulomatous rosacea.
AB  - BACKGROUND: There is a granulomatous variant which is recognized in the rosacea
      spectrum. However, the pathogenesis of granuloma formation in rosacea has not
      been clearly demonstrated. Matrix metalloproteinases (MMPs) are required for
      recruitment of inflammatory cells and for tissue remodelling, making way for the
      development of well-organized granuloma. OBJECTIVE: The aim of this study was to
      investigate the expression of transforming growth factor (TGF)-beta, TGF-beta
      type II receptor (TbetaRII), Tumour necrosis factor (TNF)-alpha, MMP-1, 2 and 9
      in the granulomatous rosacea (GR) compared with the non-granulomatous rosacea
      (NGR) and test the hypothesis that the changes of these profiles in GR would be
      related with chronic ultraviolet radiation (UVR)-exposure. METHODS: Facial skin
      samples were obtained from 20 patients with GR and NGR (control group). The
      sections were stained using haematoxylin and eosin, Verhoeff's elastic stain, and
      antibodies to TGF-beta, TbetaRII, TNF-alpha, MMP-1, -2 and -9. RESULTS: The
      amount of elastotic material was significantly increased in the dermis of GR
      lesions. Expression of TGF-beta was significantly decreased in the epidermis of
      GR lesions compared with NGR lesions. In addition, the expression of MMP-9 was
      significantly increased in the dermis of GR lesions compared with NGR lesions,
      especially at the centre of the granuloma on a semi-quantitative analysis. MMP-2
      expression was also increased in GR lesions, although the difference between the
      two groups was not statistically significant. CONCLUSIONS: The results of this
      study suggest that the increased expression of MMPs in the dermis may participate
      in granuloma formation of GR in association with UVR.

PMID- 20698914
TI  - Subungual ectopic hair.

PMID- 20698915
TI  - Structural correlations between dermoscopic and histopathological features of
      juvenile xanthogranuloma.
AB  - Juvenile xanthogranuloma(JXG) is the variant of non-Langerhans' cell
      histiocytosis. The orange-yellow background coloration with clouds of paler
      yellow deposits is the most characteristic dermoscopic finding of JXG. Other
      dermoscopic features include erythematous border, subtle pigment network and
      white linear streak. The objective of this study was to present the structural
      correlation between dermoscopic features and histopathological findings of JXG
      and to find the different dermoscopic features in various stages of JXG. Eleven
      patients with histologically proven JXG were examined with polarized light
      dermoscopy. Histopathological findings were assessed and dermoscopic features
      including setting sun appearance, clouds of paler yellow globules, whitish
      streak, and branched and linear vessels were evaluated. Among 11 patients, five
      patients were in early evolutionary stage, four patients in fully developed stage
      and two in late regressive stage. The setting sun appearance was found in all
      patients in different stages except one in late regressive stage (90.9%). The
      clouds of paler yellow globules were present in nine patients (81.8%) and were
      constant features in fully developed stage and late regressive stage. The whitish
      streak was present in four patients (36.4%) and telangiectasia in 10 patients
      (81.8%). The setting sun appearance may hold diagnostic value in early
      evolutionary stage to fully developed stage, but not in late regressive stage.
      The clouds of paler yellow globules are more predominant in fully developed stage
      and late regressive stage. In addition to the use of dermoscopy as an accurate
      diagnostic tool for differential diagnosis, it could be applied in evaluation of
      histopathological maturation of JXG.

PMID- 20698916
TI  - Information requisition is the core of guideline-based medical care: which
      information is needed for whom?
AB  - RATIONALE, AIMS AND OBJECTIVES: It is mandatory for the design of an efficient
      software product to know the different groups of users of a software tool, the
      tasks the users want to perform with it, and the information that is required for
      it. Our goal is to establish a comprehensive information source for the
      development of a consistent software environment supporting all tasks emerging
      from the creation to the execution of a computerized clinical practice guideline
      (CPG) for different user groups. METHODS: We conducted a comprehensive literature
      review to investigate the different user groups of a computerized CPG as well as
      their specific information needs. RESULTS: We provide a complete catalogue of
      every single aspect that may be related to information needs of any party
      concerned. In particular, we give detailed information on the tasks of guideline
      modellers on the one hand, and clinical information needs (i.e. information needs
      of physicians, nurses, nurse practitioners and patients) on the other hand.
      CONCLUSION: By providing categorized information from several studies and
      publications, we establish an exhaustive information basis for the design of a
      useful software tool facilitating the formalization and the execution of a CPG.

PMID- 20698917
TI  - Connected health care: the future of health care and the role of the pharmacist.
AB  - The population of the world is ageing. As a result, the incidence of chronic
      disease is projected to increase, there are predicted shortages in health care
      workforce and budget restraints; implications for future health care provision
      are serious. The current model of health care is not equipped to deal with these
      changes. Connected health care, via the use of health informatics, disease
      management and home telehealth technologies, has been suggested as an approach to
      ease the projected strain on future health care. Evidence to date suggests a
      positive impact of the use of connected health care model; however, the majority
      of studies have overlooked the involvement of the community pharmacist. As the
      most common point of contact with primary health services for most of the
      population, the community pharmacist may be well placed to provide connected
      health care. The research to date is promising with improvements in outcomes for
      cardiovascular patients noted; however, further work is required to investigate
      the potential role the community pharmacist can play in the future of connected
      health care.

PMID- 20698919
TI  - Assessment of study quality for systematic reviews: a comparison of the Cochrane
      Collaboration Risk of Bias Tool and the Effective Public Health Practice Project
      Quality Assessment Tool: methodological research.
AB  - BACKGROUND: The Cochrane Collaboration is strongly encouraging the use of a newly
      developed tool, the Cochrane Collaboration Risk of Bias Tool (CCRBT), for all
      review groups. However, the psychometric properties of this tool to date have yet
      to be described. Thus, the objective of this study was to add information about
      psychometric properties of the CCRBT including inter-rater reliability and
      concurrent validity, in comparison with the Effective Public Health Practice
      Project Quality Assessment Tool (EPHPP). METHODS: Both tools were used to assess
      the methodological quality of 20 randomized controlled trials included in our
      systematic review of the effectiveness of knowledge translation interventions to
      improve the management of cancer pain. Each study assessment was completed
      independently by two reviewers using each tool. We analysed the inter-rater
      reliability of each tool's individual domains, as well as final grade assigned to
      each study. RESULTS: The EPHPP had fair inter-rater agreement for individual
      domains and excellent agreement for the final grade. In contrast, the CCRBT had
      slight inter-rater agreement for individual domains and fair inter-rater
      agreement for final grade. Of interest, no agreement between the two tools was
      evident in their final grade assigned to each study. Although both tools were
      developed to assess 'quality of the evidence', they appear to measure different
      constructs. CONCLUSIONS: Both tools performed quite differently when evaluating
      the risk of bias or methodological quality of studies in knowledge translation
      interventions for cancer pain. The newly introduced CCRBT assigned these studies
      a higher risk of bias. Its psychometric properties need to be more thoroughly
      validated, in a range of research fields, to understand fully how to interpret
      results from its application.

PMID- 20698918
TI  - The design of patient decision support interventions: addressing the theory
      practice gap.
AB  - BACKGROUND: Although an increasing number of decision support interventions for
      patients (including decision aids) are produced, few make explicit use of theory.
      We argue the importance of using theory to guide design. The aim of this work was
      to address this theory-practice gap and to examine how a range of selected
      decision-making theories could inform the design and evaluation of decision
      support interventions. METHODS: We reviewed the decision-making literature and
      selected relevant theories. We assessed their key principles, theoretical
      pathways and predictions in order to determine how they could inform the design
      of two core components of decision support interventions, namely, information and
      deliberation components and to specify theory-based outcome measures. RESULTS:
      Eight theories were selected: (1) the expected utility theory; (2) the conflict
      model of decision making; (3) prospect theory; (4) fuzzy-trace theory; (5) the
      differentiation and consolidation theory; (6) the ecological rationality theory;
      (7) the rational-emotional model of decision avoidance; and finally, (8) the
      Attend, React, Explain, Adapt model of affective forecasting. Some theories have
      strong relevance to the information design (e.g. prospect theory); some are more
      relevant to deliberation processes (conflict theory, differentiation theory and
      ecological validity). None of the theories in isolation was sufficient to inform
      the design of all the necessary components of decision support interventions. It
      was also clear that most work in theory-building has focused on explaining or
      describing how humans think rather than on how tools could be designed to help
      humans make good decisions. It is not surprising therefore that a large theory
      practice gap exists as we consider decision support for patients. There was no
      relevant theory that integrated all the necessary contributions to the task of
      making good decisions in collaborative interactions. DISCUSSION: Initiatives such
      as the International Patient Decision Aids Standards Collaboration influence
      standards for the design of decision support interventions. However, this
      analysis points to the need to undertake more work in providing theoretical
      foundations for these interventions.

PMID- 20698920
TI  - The German version of the Assessment of Chronic Illness Care: instrument
      translation and cultural adaptation.
AB  - BACKGROUND: In Switzerland, there is a dearth of information on the extent to
      which patients with chronic illnesses receive care congruent with the Chronic
      Care Model (CCM). To drive quality improvement programmes, it is necessary to
      have practical assessment tools in the country's own language to evaluate the
      delivery of CCM activities. METHODS: German translation and adaptation of the
      original Assessment of Chronic Illness Care (ACIC). We followed a sequential
      forward and backward translation approach. In a multidisciplinary committee
      review the original English version and the translations were compared,
      instructions and formats modified and cross-cultural equivalences verified. The
      second version was pre-tested and multidisciplinary group discussion led to the
      final version which aimed to create a comprehensive culturally adapted
      translation capturing the original idea of the items rather than a direct one to
      one translation. RESULTS: Difficulties encountered during the translation process
      consisted in the difference of health care settings and health care organization
      in Switzerland and USA.The adapted German version was delivered to a managed care
      organization in the city of Zurich to test the initial use for diabetes care. The
      average ACIC subscale scores were: organization of the health care delivery
      system: mean (m) = 7.31 (SD = 0.79), community linkages: m = 3.78 (SD = 1.09),
      self-management support: m = 4.88 (SD = 1.21), decision support: m = 4.79 (SD =
      1.16), delivery system design: m = 5.56 (SD = 1.28) and clinical information
      systems: m = 4.50 (SD = 2.69). Overall, the ACIC subscale scores were comparable
      with the scores of the original testing. CONCLUSION: After cultural adaptations
      the German version of the ACIC is applicable as a tool to guide quality
      improvement in chronic illness care in German speaking countries in Europe.

PMID- 20698921
TI  - Quality of care for diabetes patients using National Health Insurance claims data
      in Japan.
AB  - BACKGROUND: Assessment of the quality of care is a key element in current
      diabetes care. However, the quality of care for diabetes patients in Japan has
      rarely been reported. OBJECTIVES: To assess the quality of diabetes care in two
      communities in Japan by using National Health Insurance claims data. METHODS: We
      analysed claim data of 13,650 beneficiaries of National Health Insurance in two
      communities in Japan from May 2006 to April 2007. Diabetes cases were identified
      by using a case detection algorism. Our main outcome measures were three process
      quality indicators: (1) haemoglobin A1c (HbA1c) testing; (2) annual eye
      examination; and (3) annual nephropathy screening, recommended in the existing
      clinical guidelines. We calculated the performance rate of each quality indicator
      and examined the effects of demographic characteristics and co-morbid conditions.
      RESULTS: We identified 636 diabetes cases. Of these, 97.0% had at least one HbA1c
      test, and 69.8% had >= 4 tests during the study period. The odds ratios (ORs) for
      >= 4 HbA1c tests were lower in subgroups aged 75-79 (OR 0.58, 95% confidence
      interval 0.35-0.96), and aged >= 80 (OR 0.54, 95% confidence interval 0.32-0.88)
      compared with the subgroup aged <70 after adjusting for other patient
      characteristics. The annual rate for eye examinations and nephropathy screenings
      were 20.8% and 5.8% respectively. CONCLUSIONS: We found high performance rates
      for HbA1c testing, while the annual rates for eye examinations and nephropathy
      screenings were suboptimal. Using administrative data would facilitate more
      comprehensive assessment of the quality of care in Japan.

PMID- 20698922
TI  - Metabolic rates, genetic constraints, and the evolution of endothermy.
AB  - The metabolic distinction between endotherms and ectotherms is profound. Whereas
      the ecology of metabolic rates is well studied, how endotherms evolved from their
      ectothermic ancestors remains unclear. The aerobic capacity model postulates that
      a genetic constraint between resting and maximal metabolism was essential for the
      evolution of endothermy. Using the multivariate breeders' equation, I illustrate
      how the (i) relative sizes of genetic variances and (ii) relative magnitudes of
      selection gradients for resting and maximal metabolism affect the genetic
      correlation needed for endothermy to have evolved via a correlated response to
      selection. If genetic variances in existing populations are representative of
      ancestral conditions, then the aerobic capacity model is viable even if the
      genetic correlation was modest. The analyses reveal how contemporary data on
      selection and genetic architecture can be used to test hypotheses about the
      evolution of endothermy, and they show the benefits of explicitly linking
      physiology and quantitative genetic theory.

PMID- 20698923
TI  - Mental Health Services for Adults with Intellectual Disability.

PMID- 20698924
TI  - Clinical utility of systemic venous sampling of FGF23 for identifying tumours
      responsible for tumour-induced osteomalacia.

PMID- 20698925
TI  - Orthostatic hypotension and long-term incidence of atrial fibrillation: the Malmo
      Preventive Project.
AB  - OBJECTIVES: Orthostatic hypotension (OH), a common manifestation of autonomic
      dysfunction, has been identified as an independent risk factor for all-cause
      mortality and incident cardiovascular disease. However, the role of OH in the
      development of atrial fibrillation has not been studied. DESIGN: We investigated
      the incidence of atrial fibrillation in relation to baseline presence of OH
      according to international consensus criteria in the Swedish population-based
      prospective cohort of the Malmo Preventive Project. The study sample consisted of
      33,346 individuals (67.3% men; mean age, 45.6 +/- 7.4 years; range, 26-61 years).
      The association between OH and incidence of atrial fibrillation during follow-up
      was assessed using the Kaplan-Meier method and multivariable Cox proportional
      hazard models, taking into account conventional risk factors for atrial
      fibrillation. RESULTS: At baseline, 1987 participants (6.1%) met the diagnostic
      criteria for OH. Over a follow-up period of approximately 24 years, 2312
      individuals (3.0 events/1000 person-years) were diagnosed with new-onset atrial
      fibrillation. Of these, 196 had OH at baseline (4.6 events/1000 person-years
      amongst all OH-positive individuals). In a multivariable Cox regression analysis,
      OH predicted incidence of atrial fibrillation independently of other risk factors
      (hazard ratio [HR]: 1.30; 95% confidence interval [CI]: 1.05-1.61; P = 0.016),
      and this association was significant in hypertensive (HR: 1.44; 95%CI: 1.10-1.88;
      P = 0.008), but not in normotensive participants (HR: 1.10; 95%CI: 0.77-1.58; P =
      0.60). CONCLUSIONS: The presence of OH predicts the incidence of atrial
      fibrillation in middle-aged hypertensive individuals, independently of
      conventional risk factors. Further studies of the association of autonomic
      dysfunction and OH with atrial fibrillation are needed.

PMID- 20698926
TI  - Rapid increase in myocardial infarction risk following diagnosis of rheumatoid
      arthritis amongst patients diagnosed between 1995 and 2006.
AB  - The risk of ischaemic heart disease (IHD), and in particular myocardial
      infarction (MI), is increased amongst patients with established rheumatoid
      arthritis (RA). Few studies have included contemporary patients with RA. We
      recently reported that the risk of IHD is not elevated before the onset of RA
      symptoms. However, when, in relation to RA diagnosis, the risk is increased is
      unknown. OBJECTIVE: To assess the risk of MI and other IHD events amongst
      patients diagnosed with RA during the last decade and within 18 months following
      RA symptom onset, compared to the general population, by time since RA diagnosis,
      year of RA diagnosis and by rheumatoid factor (RF) status. METHODS AND PATIENTS:
      A Swedish inception cohort of RA (n = 7469) diagnosed between 1995 and 2006 and a
      matched general population comparator cohort (n = 37,024), was identified and
      linked to national registers of morbidity and mortality from IHD. Relative risks
      (RRs) of MI and other IHD events were estimated using Cox regression. RESULTS:
      During follow-up, 233 patients with RA and 701 controls developed a first MI,
      corresponding to an overall RR of MI of 1.6 (95% confidence interval 1.4, 1.9).
      Increased risks of MI were already detected within 1-4 years following RA
      diagnosis, as well as in patients diagnosed with RA during the last 5 years, in
      RF-negative patients and for transmural as well as nontransmural MIs.
      CONCLUSIONS: MI risk increases rapidly following RA diagnosis, suggesting the
      importance of additional mechanisms other than atherosclerosis. The elevated
      short-term risk is present amongst patients diagnosed in recent years,
      underscoring the importance of MI prevention from the time of RA diagnosis.

PMID- 20698927
TI  - Combined analyses and extended follow-up of two randomized controlled
      homocysteine-lowering B-vitamin trials.
AB  - OBJECTIVES: In the Norwegian Vitamin Trial and the Western Norway B Vitamin
      Intervention Trial, patients were randomly assigned to homocysteine-lowering B
      vitamins or no such treatment. We investigated their effects on cardiovascular
      outcomes in the trial populations combined, during the trials and during an
      extended follow-up, and performed exploratory analyses to determine the
      usefulness of homocysteine as a predictor of cardiovascular outcomes. DESIGN:
      Pooling of data from two randomized controlled trials (1998-2005) with extended
      post-trial observational follow-up until 1 January 2008. SETTING: Thirty-six
      hospitals in Norway. SUBJECTS: 6837 patients with ischaemic heart disease.
      INTERVENTIONS: One capsule per day containing folic acid (0.8 mg) plus vitamin
      B12 (0.4 mg) and vitamin B6 (40 mg), or folic acid plus vitamin B12, or vitamin
      B6 alone or placebo. MAIN OUTCOME MEASURES: Major adverse cardiovascular events
      (MACEs; cardiovascular death, acute myocardial infarction or stroke) during the
      trials and cardiovascular mortality during the extended follow-up. RESULTS: Folic
      acid plus vitamin B12 treatment lowered homocysteine levels by 25% but did not
      influence MACE incidence (hazard ratio, 1.07; 95% CI, 0.95-1.21) during 39 months
      of follow-up, or cardiovascular mortality (hazard ratio, 1.12; 95% CI, 0.95-1.31)
      during 78 months of follow-up, when compared to no such treatment. Baseline
      homocysteine level was not independently associated with study outcomes. However,
      homocysteine concentration measured after 1-2 months of folic acid plus vitamin
      B12 treatment was a strong predictor of MACEs. CONCLUSION: We found no short- or
      long-term benefit of folic acid plus vitamin B12 on cardiovascular outcomes in
      patients with ischaemic heart disease. Our data suggest that cardiovascular risk
      prediction by plasma total homocysteine concentration may be confined to the
      homocysteine fraction that does not respond to B-vitamins.

PMID- 20698928
TI  - Potential CYP2C9-mediated drug-drug interactions in hospitalized type 2 diabetes
      mellitus patients treated with the sulphonylureas glibenclamide, glimepiride or
      glipizide.
AB  - OBJECTIVES: Sulphonylureas are widely used in the treatment of type 2 diabetes
      mellitus (T2DM). Based on laboratory findings, we determined the clinical
      significance of potential CYP2C9-mediated drug-drug interactions in hospitalized
      patients receiving glibenclamide, glimepiride or glipizide, all of which are
      metabolized by CYP2C9, together with a CYP2C9 inhibitor. DESIGN, SETTING AND
      SUBJECTS: An observational pharmaco-epidemiological database study was performed
      in a university hospital setting with 3884 patients with T2DM. MAIN OUTCOME
      MEASURES: Efficacy and safety of sulphonylurea therapy during the potential
      interaction (sulphonylurea treatment with a CYP2C9 inhibitor) vs. control periods
      (sulphonylurea treatment without a CYP2C9 inhibitor) were estimated using
      laboratory parameters. RESULTS: Almost 20% of patients were exposed to a
      potential drug-drug interaction with a CYP2C9 inhibitor during sulphonylurea
      treatment. More than 75% of the potential interactions occurred with
      trimethoprim, metronidazole and fluconazole. When all sulphonylureas were pooled
      and adjusted for age, gender, ward and sulphonylurea dose, mean and maximum
      fasting plasma glucose concentrations as well as maximum values of glycosylated
      haemoglobin were significantly lower during the interaction periods compared with
      control periods, whereas mean and minimum activities of alanine amino transferase
      and gamma-glutamyl transferase were higher. The minimum fasting plasma glucose
      values were more often below the target range in patients with potential
      interactions. The sulphonylurea dose did not differ significantly between
      patients who were or were not concomitantly treated with a potentially
      interacting drug. CONCLUSIONS: Concomitant use of a CYP2C9 inhibitor results in
      exaggerated pharmacodynamic effects of sulphonylureas and increases the risk of
      hypoglycaemia in T2DM patients receiving glibenclamide, glimepiride or glipizide.

PMID- 20698929
TI  - Flow cytometric characterization of the lymphocyte composition in a variety of
      mucosal tissues in healthy rhesus macaques.
AB  - BACKGROUND: Rhesus monkeys play a central role in model studies on human
      infectious diseases, and often mucosal organs are affected by these pathogens,
      e.g. HIV. However, a comparative investigation into lymphocyte composition from
      different mucosal tissues is still missing. METHODS: Lymphocyte composition of
      duodenum, jejunum, ileum, colon, vagina, cervix, uterus and bronchoalveolar
      lavage from healthy rhesus monkeys was characterized in detail by flow cytometry.
      Moreover, we compared the lymphocyte proportions from intestinal biopsies with
      resections. RESULTS: All mucosal tissues exhibited higher values of CD8(+) ,
      CD4(+) CCR5(+) and CD45RA(-) memory T cells than blood, but similar levels of
      total T cells. Especially within the four gut sites, the lymphocyte composition
      varied significantly. The relative proportions of lymphocyte subsets from
      duodenal and colonic biopsies compared to resections differed. CONCLUSION: The
      lymphocyte composition highly varies between different mucosal sites, and data
      obtained from biopsy and necropsy samples were mostly not comparable.

PMID- 20698930
TI  - Unilateral ovarian absence in two capuchin monkeys.
AB  - BACKGROUND: Ovarian absence is a rare condition with congenital or traumatic
      origin. METHODS: Gross and microscopic examination of two capuchin monkeys were
      performed. RESULTS: Case 1 had absence of the right ovary and distal uterine
      tube, bilateral absence of fimbriae, and a rudimentary uterus. Case 2 had
      unilateral ovarian absence, but a functional contralateral ovary, and a normal
      uterus. CONCLUSIONS: Unilateral ovarian absence was confirmed in two capuchin
      monkeys for the first time.

PMID- 20698931
TI  - The biphasic NAD(P)H fluorescence response of astrocytes to dopamine reflects the
      metabolic actions of oxidative phosphorylation and glycolysis.
AB  - The NAD(+)/NADH redox pair constitutes an important metabolic node connecting
      catabolic pathways to energy production. We took advantage of the fluorescence of
      NADH to monitor changes in NADH levels by 2-photon laser scanning microscopy in
      cultured cortical astrocytes and acutely isolated brain slices in response to
      dopamine (DA), a major neurotransmitter involved in modulation of attention,
      motivation, and learning. DA induced a dose-dependent biphasic response of the
      NAD(P)H fluorescence signal, consisting of an initial decrease followed by a
      subsequent increase. This response was mediated by D1-receptors, protein kinase
      A, and 5'-AMP-activated protein kinase signaling. While the initial decrease
      could be inhibited by blocking mitochondrial respiratory chain, the increase was
      inhibited by blocking glycolysis. Finally, activation of DA receptors on
      astrocytes in acutely isolated mouse cortical brain slices also induced an
      increase in the NAD(P)H fluorescence signal. We conclude that DA activates two
      opposing components of astrocytic metabolism with different kinetics. This
      response of the astroglial metabolism might contribute to fine-tuned
      participation of astrocytes to neuronal activity and functional states of the
      brain.

PMID- 20698932
TI  - The hAPP-YAC transgenic model has elevated UPS activity in the frontal cortex
      similar to Alzheimer's disease and Down's syndrome.
AB  - The ubiquitin-proteasome system (UPS) is critical for handling the intra-cellular
      load of abnormal and misfolded proteins in several neurodegenerative diseases.
      First, to determine the effects of the over-expression of human amyloid precursor
      protein (hAPP) on UPS, we measured proteasome activities using fluorescent
      substrates in the frontal cortex of hAPP-yeast artificial chromosome (YAC)
      transgenic (tg) mice (R1.40, hemizygous; Lamb, Nat Genet, 9, 4; 1995).
      Chymotrypsin and PGPH-like activities of proteasome were increased in frontal
      cortex of hAPP-YAC tg mice. These proteasome activities (both chymotrypsin and
      PGPH-like) were further increased by cholinergic stimulation in littermate
      control mice, but not in hAPP-YAC tg mice. Nerve growth factor (NGF) levels were
      decreased by hAPP over-expression in the frontal cortex and hippocampus of hAPP
      YAC tg mice, and further decreased by M1 agonist treatment in the hippocampus of
      littermate control and hAPP-YAC tg mice. Interestingly, the frontal cortex (BA9
      area) of Alzheimer's disease (AD) patients (Stage 3, n=11) and Down's syndrome
      (DS) patients (n=9) showed similar up-regulation of the UPS activities to those
      seen in hAPP-YAC tg mice. M1 agonist stimulation increased the activities of
      alpha-secretase, which were down-regulated by hAPP over-expression in the frontal
      cortex of hAPP-YAC tg mice. These results demonstrate that (i) hAPP-YAC tg mice
      have an up-regulation in the frontal cortex of the UPS similar to AD and DS
      patients; (ii) muscarinic stimulation increase UPS activities, increase secreted
      APP (APPs) levels, and decrease amyloid beta 42/40 ratio only in littermate
      controls, but not in hAPP-YAC tg mice. Taken together, these results suggest that
      both the adaptive reactions in the proteostatic network and pathological changes
      in AD and DS need to be considered in the future potential therapeutics.

PMID- 20698933
TI  - Smoking and women's health.

PMID- 20698934
TI  - Breast cancer screening.

PMID- 20698935
TI  - Advanced cardiac life support in obstetric settings.

PMID- 20698936
TI  - Sleep variety: physiology, psychology and epidemiology.

PMID- 20698938
TI  - Desensitization for renal transplantation: depletion of donor-specific anti-HLA
      antibodies, preservation of memory antibodies, and clinical risks.
AB  - Desensitization protocols reduce donor-specific anti-HLA antibodies (DSA) and
      enable renal transplantation in patients with a positive complement-dependent
      cytotoxic cross-match (CDC-CXM). The effect of this treatment on protective
      antibody and immunoglobulin levels is unknown. Thirteen patients with end-stage
      renal disease, DSA and positive CDC-CXM underwent desensitization. Sera collected
      pre- and post-transplantation were analysed for anti-tetanus and anti
      pneumococcal antibodies, total immunoglobulin (Ig) levels and IgG subclasses and
      were compared to healthy controls and contemporaneous renal transplant recipients
      treated with standard immunosuppression alone. Ten patients developed negative
      CDC-CXM and enzyme-linked immunosorbent assay (ELISA) and underwent successful
      transplantation. Eight recipients achieved good graft function without antibody
      mediated or late rejection, BK virus or cytomegalovirus infection. One patient
      had primary non-function due to recurrent oxalosis, and one patient with
      immediate graft function died from septicaemia. Seven recipients required post
      operative transfusion and three developed septicaemia. DSA remained negative by
      ELISA at 12 months, but were detectable by Luminex((r)) . Anti-tetanus and anti
      pneumococcal antibodies, total Ig and IgG subclasses were below the normal range
      but comparable to levels in renal transplant recipients who had not undergone
      desensitization. Desensitization protocols effectively reduce DSA and allow
      successful transplantation. Post-operative bleeding and short-term infectious
      risk is increased. Protective antibody and serum immunoglobulin levels are
      relatively preserved.

PMID- 20698939
TI  - Disseminated nocardiosis caused by Nocardia abscessus in a dog.
AB  - A 4-year-old female spayed Bichon Frise dog that had been receiving cyclosporine
      A per os 3 times per week for 2 months to control allergic dermatitis developed
      lethargy, anorexia, fever, and multiple firm subcutaneous masses.
      Pyogranulomatous inflammation with branching nonseptate filamentous organisms
      approximately 2 MUm in diameter, presumptively fungal organisms, was diagnosed by
      cytologic evaluation of fine-needle aspirates from several masses. A partially
      acid-fast actinomycete was cultured from 2 of the masses. The organism was
      identified as Nocardia abscessus (formerly Nocardia asteroides type 1) based on
      16S ribosomal DNA sequencing of samples extracted from cultures and unstained
      cytologic smears. Immunosuppression caused by long-term administration of
      cyclosporine A likely predisposed the dog to disseminated infection. To our
      knowledge, this is the first report of N. abscessus infection in a dog. This case
      demonstrates that N. abscessus may be mistaken for a fungal organism based on its
      cytologic appearance and underscores the importance of using molecular techniques
      for the diagnosis of suspected fungal diseases.

PMID- 20698940
TI  - Detection of Neospora caninum tachyzoites in cerebrospinal fluid of a dog
      following prednisone and cyclosporine therapy.
AB  - A 9-year-old female spayed Shetland Sheepdog was presented to the Kansas State
      University Veterinary Medical Teaching Hospital for evaluation following a 3-week
      history of left rear limb lameness that had progressed to generalized ataxia.
      Multifocal or diffuse brain lesions were suspected based on physical examination
      findings. Cerebrospinal fluid (CSF) contained 52 nucleated cells/MUL composed of
      mixed inflammatory cells. Treatment with prednisone and cyclosporine was
      initiated based on a presumptive diagnosis of granulomatous meningoencephalitis.
      Thirteen days later the dog was nonambulatory and mentally obtunded. Repeat CSF
      analysis revealed 298 nucleated cells/MUL with 61% eosinophils. Rare protozoal
      tachyzoites consistent with Neospora caninum, Toxoplasma gondii, or Sarcocystis
      spp. were found extracellularly and within macrophages and an eosinophil. Despite
      cessation of prednisone and cyclosporine therapy and provision of supportive
      care, the dog died 6 days later. Examination of brain tissue sections revealed
      multifocally extensive, necrotizing, histiocytic, and lymphoplasmacytic
      meningoencephalitis with numerous protozoal zoites and cysts. Immunohistochemical
      analysis of brain tissue using a monoclonal antibody specific for N. caninum
      confirmed the diagnosis of neosporosis. Similar but less severe lesions were
      noted in the spinal cord, although organisms were not found. This case emphasizes
      the value of repeated CSF analysis when therapy is ineffective and the importance
      of excluding infectious causes of meningoencephalitis before commencement of
      immunosuppressive therapy.

PMID- 20698941
TI  - Analytical validation of an ELISA for measurement of canine pancreas-specific
      lipase.
AB  - BACKGROUND: The diagnosis of canine pancreatitis is challenging. Clinical
      presentation often includes nonspecific clinical signs, such as vomiting,
      anorexia, and abdominal discomfort. Increased serum lipase activity can be
      indicative of pancreatitis; however, it can also be increased with other
      conditions. An immunoassay for measurement of canine pancreas-specific lipase in
      canine serum that would be suitable for commercial application and provide rapid
      results would be beneficial. OBJECTIVE: The goal of this study was to validate
      the Spec cPL assay, a commercially available ELISA for the quantitative
      measurement of canine pancreas-specific lipase. METHODS: Dynamic range,
      dilutional linearity, precision, interfering substances, assay stability, and
      reproducibility were investigated for analytical validation. The method was
      compared with the reference assay, canine pancreatic lipase immunoreactivity
      (cPLI), and included evaluation of a sample population of dogs and bias. RESULTS:
      Analytical validation showed a dynamic range of 36-954 MUg/L; good precision
      (intra- and interassay coefficient of variation <12%); absence of interference
      from lipid, hemoglobin, or bilirubin; 12-month kit stability; and good
      reproducibility. Method comparison showed a positive bias relative to the cPLI
      reference method; however, the bias can be accommodated by adjustment of decision
      limits. The upper limit of the reference interval for Spec cPL was determined to
      be 216 MUg/L based on the upper 97.5th percentile of results from 93 clinically
      healthy, kennel-housed dogs. CONCLUSIONS: Validation data demonstrated that the
      Spec cPL assay provides reproducible results for canine pancreas-specific lipase.
      A readily available assay for measurement of this enzyme allows broader clinical
      utilization of this analytical tool, generating timely results to aid in the
      diagnosis of canine pancreatitis.

PMID- 20698942
TI  - Metastatic pancreatic polypeptide-secreting islet cell tumor in a dog.
AB  - A 14-year-old female spayed Golden Retriever was presented to the University of
      Florida's Veterinary Medical Center with history of lymphoplasmacytic
      gastroenteritis, intermittent vomiting, watery diarrhea, and weight loss for over
      a year. CBC, biochemical profile, and urinalysis were within reference intervals.
      Abdominal ultrasonographic examination revealed mesenteric and jejunal
      lymphadenopathy and hyperechoic hepatic nodules. Cytologic examination of the
      enlarged lymph nodes revealed loosely cohesive cells with moderate nuclear
      pleomorphism and rare punctate eosinophilic cytoplasmic granules. The cytologic
      interpretation was metastatic neuroendocrine neoplasia. On surgical exploration,
      a mass was detected in the right lobe of the pancreas. Histologic evaluation
      determined the mass to be an islet cell tumor. Approximately 98% of cells were
      positive by immunolabeling for pancreatic polypeptide (PP), and only rare cells
      were positive for insulin or somatostatin. All cells were negative for glucagon,
      gastrin, vasoactive intestinal polypeptide, protein gene product 9.5,
      synaptophysin, and chromogranins A and B. Pancreatic tumors that primarily
      produce PP are rare in dogs, and this is the first report of both the cytologic
      and histologic features of an islet cell tumor predominantly secreting PP.
      Clinical signs for these tumors are typically absent or nonspecific; signs may
      include watery diarrhea, as noted in this dog, although the diarrhea may have
      resulted from lymphoplasmacytic gastroenteritis. Additional case studies are
      needed to further characterize the cytomorphologic features and clinical
      presentation of PP-secreting islet cell tumor, or polypeptidoma, in dogs.

PMID- 20698943
TI  - Electrophoretic fractionation of creatine kinase isoenzymes and macroenzymes in
      clinically healthy dogs and cats and preliminary evaluation in central neurologic
      disease.
AB  - BACKGROUND: Information about the electrophoretic distribution of CK-MM, CK-MB,
      and CK-BB, serum creatine kinase (CK) isoenzymes that are indicators of skeletal
      muscle, cardiac muscle, and brain lesions, respectively, and CK macroenzymes
      (macro-CK1 and macro-CK2) in dogs and cats with and without central neurologic
      disease is scant and equivocal. OBJECTIVES: The objectives of this study were to
      describe the electrophoretic distribution of CK isoenzymes and macroenzymes in
      healthy dogs and cats and to provide a preliminary assessment of the utility of
      CK enzymatic electrophoresis in dogs and cats with central neurologic disease.
      METHODS: Electrophoretic separation of serum CK isoenzymes and macroenzymes was
      performed on freeze-thawed serum samples from 20 healthy dogs and 3 dogs with
      central neurologic disease and from 14 healthy cats and 6 cats with neurologic
      feline infectious peritonitis (FIP). Electrophoretic separation was also
      performed on supernatants of homogenized brain, skeletal muscle, and cardiac
      muscle from both species, to assess the tissue distribution of isoenyzmes in dogs
      and cats. RESULTS: CK-MM was the predominant isoenzyme in the serum of healthy
      dogs and cats, followed by macro-CK2 and CK-BB in dogs and by both macroenzymes
      in cats. In dogs, CK-MB was essentially absent from both serum and homogenized
      hearts. CK-BB increased in dogs with neurologic disease. In cats, CK-BB was
      essentially absent from serum, but was present in brain homogenates. Two of 6
      cats with FIP had increased macro-CK1 and increased CK-BB activity. CONCLUSIONS:
      This study identified the electophoretic distribution of CK isoenzymes and
      macroenzymes of dogs and cats and provided encouraging data about the possible
      use of CK-BB as a biomarker for canine neurologic disorders, but not for FIP.

PMID- 20698945
TI  - Leptospirosis presenting in a woman with fulminant hepatic failure from Wilson's
      disease: a case report.
AB  - INTRODUCTION: We report an unusual case of Wilson's disease that was revealed by
      presentation of leptospirosis. The prompt detection of this potentially life
      threatening disease highlights the importance of careful investigation. To the
      best of our knowledge, this is the first reported case of leptospirosis involving
      the development of fulminant liver failure due to Wilson's disease. CASE
      PRESENTATION: A 17-year-old Caucasian woman presented with fever, rigors,
      vomiting and scleral jaundice. Following clinical and laboratory evaluation she
      was diagnosed with leptospirosis. After remission of this disease her condition
      inexplicably deteriorated. Further investigations revealed that she had Wilson's
      disease. CONCLUSIONS: The unexplained deterioration of hepatic function in a
      young person in remission from leptospirosis should alert the clinician to the
      presence of an underlying disorder, such as Wilson's disease, the early detection
      of which is crucial to the prognosis. The mechanism that initiates the
      development of Wilson's disease is not fully understood, but it is thought that
      an intercurrent illness, such as viral infection or drug toxicity, could be
      implicated. In our case, leptospirosis appeared to precipitate the deterioration
      of liver function in a patient with Wilson's disease, advancing our knowledge of
      this association. This original case report could have a broader clinical impact
      across medicine.

PMID- 20698946
TI  - Recurrent lower gastrointestinal bleeding from idiopathic ileocolonic varices: a
      case report.
AB  - INTRODUCTION: Varices of the colon are a rare cause of lower gastrointestinal
      bleeding, usually associated with portal hypertension due to liver cirrhosis or
      other causes of portal venous obstruction. Idiopathic colonic varices are
      extremely rare. Recognition of this condition is important as idiopathic colonic
      varices may be a cause of recurrent lower gastrointestinal bleeding. CASE
      PRESENTATION: We report the case of a 21-year-old Asian man from north India who
      presented with recurrent episodes of lower gastrointestinal bleeding. Colonoscopy
      revealed varices involving the terminal ileum and colon to the sigmoid. Thorough
      evaluation was undertaken to rule out any underlying portal hypertension. Our
      patient underwent subtotal colectomy including resection of involved terminal
      ileum and an ileorectal anastomosis. CONCLUSION: Colonic varices are an uncommon
      cause of lower gastrointestinal bleeding. Idiopathic colonic varices are
      diagnosed after excluding underlying liver disease and portal hypertension.
      Recognition of this condition is important as prognosis is good in the absence of
      liver disease and is curable by resection of the involved bowel.

PMID- 20698947
TI  - Benign cervical multi-nodular goiter presenting with acute airway obstruction: a
      case report.
AB  - INTRODUCTION: Benign cervical goiters rarely cause acute airway obstruction. CASE
      PRESENTATION: We report the case of a 64-year-old woman of African descent who
      presented with acute shortness of breath. She required immediate intubation and
      later a total thyroidectomy for a benign cervical multi-nodular goiter with no
      retrosternal tracheal compression. CONCLUSION: Benign multi-nodular goiters are
      commonly left untreated once euthyroid. Peak inspiratory flow rates should be
      measured via spirometry in all goiters to assess the degree of tracheal
      compression. Once tracheal compression is identified, an elective total
      thyroidectomy should be performed to prevent morbidity and mortality from acute
      airway obstruction.

PMID- 20698948
TI  - Sarcoidosis in a dental surgeon: a case report.
AB  - INTRODUCTION: Although the causes of sarcoidosis are still unknown, past and
      current studies have provided evidence that this disease may be associated with
      occupational exposure to specific environmental agents. We describe a case of
      sarcoidosis in a dental surgeon with long exposure to inorganic dusts. To the
      best of our knowledge, this is the first report of this kind in the literature.
      CASE PRESENTATION: At the beginning of 2000, a 52-year-old Caucasian man, who
      worked as a dental surgeon, presented with shortness of breath during exercise,
      cough and retrosternal pain. After diagnosis of sarcoidosis, a scanning
      electronic microscopy with X-ray microanalysis of biopsy specimens was used in
      order to determine whether the disease could be traced to an occupational
      environmental agent. Results showed the presence of inorganic dust particles
      within sarcoidotic granulomas, and demonstrated that the material detected was
      identical to that found in a powder used by our patient for several years.
      CONCLUSIONS: Although these results cannot be considered as definitive proof,
      they do however provide strong evidence that this disease may be associated with
      material used by dental surgeons.

PMID- 20698949
TI  - Anti-HCV reactive volunteer blood donors distribution character and genotypes
      switch in Xi'an, China.
AB  - HCV is prevailed in the world as well as in China. Blood transfusion is one of
      the most common transmission pathways of this pathogen. Although data of HCV
      infection character were reported during the past years, anti-HCV reactive
      profile of China donors was not fully clear yet. Furthermore, infection progress
      was found related to the HCV genotype. Different genotype led to different
      efficacy when interferon was introduced into HCV therapy. Here we provided
      character data of HCV infection in China blood donors from the year of 2000 to
      2009. The infection rate in local donors was lower than general population and
      descended from 0.80% to 0.40% or so in recent years. About 83% HCV strains were
      categorized into genotypes 1b and 2a. But 1b subtype cases climbed and 2a subtype
      cases decreased. The current study threw more light on HCV infection of blood
      donors in China, at least in the Northern region.

PMID- 20698950
TI  - NOD2-C2 - a novel NOD2 isoform activating NF-kappaB in a muramyl dipeptide
      independent manner.
AB  - BACKGROUND: The innate immune system employs several receptor families that form
      the basis of sensing pathogen-associated molecular patterns. NOD (nucleotide
      binding and oligomerization domain) like receptors (NLRs) comprise a group of
      cytosolic proteins that trigger protective responses upon recognition of
      intracellular danger signals. NOD2 displays a tandem caspase recruitment domain
      (CARD) architecture, which is unique within the NLR family. FINDINGS: Here, we
      report a novel alternative transcript of the NOD2 gene, which codes for a
      truncated tandem CARD only protein, called NOD2-C2. The transcript isoform is
      highest expressed in leucocytes, a natural barrier against pathogen invasion, and
      is strictly linked to promoter usage as well as predominantly to one allele of
      the single nucleotide polymorphism rs2067085. Contrary to a previously identified
      truncated single CARD NOD2 isoform, NOD2-S, NOD2-C2 is able to activate NF-kappaB
      in a dose dependent manner independently of muramyl dipeptide (MDP). On the other
      hand NOD2-C2 competes with MDPs ability to activate the NOD2-driven NF-kappaB
      signaling cascade. CONCLUSION: NOD2 transcripts having included an alternative
      exon downstream of exon 3 (exon 3a) are the endogenous equivalents of a
      previously described in vitro construct with the putative protein composed of
      only the two N-terminal CARDs. This protein form (NOD2-C2) activates NF-kappaB
      independent of an MDP stimulus and is a potential regulator of NOD2 signaling.

PMID- 20698951
TI  - Loss, mutation and deregulation of L3MBTL4 in breast cancers.
AB  - BACKGROUND: Many alterations are involved in mammary oncogenesis, including
      amplifications of oncogenes and losses of tumor suppressor genes (TSG). Losses
      may affect almost all chromosome arms and many TSGs remain to be identified.
      RESULTS: We studied 307 primary breast tumors and 47 breast cancer cell lines by
      high resolution array comparative genomic hybridization (aCGH). We identified a
      region on 18p11.31 lost in about 20% of the tumors and 40% of the cell lines. The
      minimal common region of loss (Chr18:6,366,938-6,375,929 bp) targeted the L3MBTL4
      gene. This gene was also targeted by breakage in one tumor and in two cell lines.
      We studied the exon sequence of L3MBTL4 in 180 primary tumor samples and 47 cell
      lines and found six missense and one nonsense heterozygous mutations. Compared
      with normal breast tissue, L3MBTL4 mRNA expression was downregulated in 73% of
      the tumors notably in luminal, ERBB2 and normal-like subtypes. Losses of the
      18p11 region were associated with low L3MBTL4 expression level. Integrated
      analysis combining genome and gene expression profiles of the same tumors pointed
      to 14 other potential 18p TSG candidates. Downregulated expression of ZFP161,
      PPP4R1 and YES1 was correlated with luminal B molecular subtype. Low ZFP161 gene
      expression was associated with adverse clinical outcome. CONCLUSION: We have
      identified L3MBTL4 as a potential TSG of chromosome arm 18p. The gene is targeted
      by deletion, breakage and mutations and its mRNA is downregulated in breast
      tumors. Additional 18p TSG candidates might explain the aggressive phenotype
      associated with the loss of 18p in breast tumors.

PMID- 20698952
TI  - Establishment of a minor groove binder-probe based quantitative real time PCR to
      detect Borrelia burgdorferi sensu lato and differentiation of Borrelia spielmanii
      by ospA-specific conventional PCR.
AB  - BACKGROUND: Borrelia burgdorferi sensu lato (sl), the causative agent of Lyme
      borreliosis, is transmitted by ticks of the genus Ixodes as vector. For
      identification of Borrelia infections in ticks a TaqMan minor groove binder (MGB)
      probe-based quantitative real time PCR (qPCR) was established targeting the 5S
      23S intergenic spacer. Extension to a duplex qPCR included an Ixodes spp.
      positive control to verify successful DNA isolation. Besides qPCR, an ospA
      specific conventional PCR for species-specific identification of B. spielmanii
      was established. Afterwards 1000 I. ricinus flagged in the city of Hanover,
      Germany, were investigated for B. burgdorferi sl infections followed by species
      identification. Furthermore, I. hexagonus ticks were investigated to proof
      applicability of the PCRs. RESULTS: Quantitative real time PCR (qPCR) identifying
      B. burgdorferi sl in ticks was able to detect 1-10 copies per reaction. B.
      spielmanii ospA-specific conventional PCR was also highly specific and showed no
      cross reactions with the other tested Borrelia species. From 1000 hanoveranian
      ticks 24.3% were positive compared to only 7.4% positives by dark-field
      microscopy. Related to tick stage 1.7% larvae, 18.1% nymphs, and 34.6% adults
      were positive. The most frequent species was B. garinii, followed by B. afzelii,
      B. spielmanii, B. valaisiana and B. burgdorferi sensu stricto (ss). 70.6% of I.
      ricinus were mono-infected, whereas 28.0% and 1.4% were infected with two and
      three Borrelia species, respectively. From 232 I. hexagonus collected from
      hedgehogs in different sites of Germany, qPCR detected 5.7% to be infected with
      B. burgdorferi sl, which were identified as B. afzelii, B. garinii and B.
      spielmanii. CONCLUSIONS: The evaluated qPCR to detect B. burgdorferi sl in Ixodes
      spp. is highly specific and sensitive. As a duplex qPCR including detection of
      Ixodes spp. DNA it is the first DNA based technique incorporating a control for
      successful DNA isolation from the vector tick. Establishment of a B. spielmanii
      specific conventional PCR filled the gap in PCR identification of principal
      European Borrelia genospecies. Practical application showed that all European
      pathogenic Borrelia spp. were present in I. ricinus flagged in recreational areas
      of the city of Hanover and confirmed I. hexagonus as reservoir for pathogenic
      Borrelia spp.

PMID- 20698953
TI  - Co-assortment in integron-associated gene cassette assemblages in environmental
      DNA samples.
AB  - BACKGROUND: It has been shown that integron-associated gene cassettes exist
      largely in tandem arrays of variable size, ranging from antibiotic resistance
      arrays of three to five cassettes up to arrays of more than 100 cassettes
      associated with the vibrios. Further, the ecology of the integron/gene cassette
      system has been investigated by showing that very many different cassettes are
      present in even small environmental samples. In this study, we seek to extend the
      ecological perspective on the integron/gene cassette system by investigating the
      way in which this diverse cassette metagenome is apportioned amongst prokaryote
      lineages in a natural environment. RESULTS: We used a combination of PCR-based
      techniques applied to environmental DNA samples and ecological analytical
      techniques to establish co-assortment within cassette populations, then
      establishing the relationship between this co-assortment and genomic structures.
      We then assessed the distribution of gene cassettes within the environment and
      found that the majority of gene cassettes existed in large co-assorting groups.
      CONCLUSIONS: Our results suggested that the gene cassette diversity of a
      relatively pristine sampling environment was structured into co-assorting groups,
      predominantly containing large numbers of cassettes per group. These co-assorting
      groups consisted of different gene cassettes in stoichiometric relationship.
      Conservatively, we then attributed co-assorting cassettes to the gene cassette
      complements of single prokaryote lineages and by implication, to large integron
      associated arrays. The prevalence of large arrays in the environment raises new
      questions about the assembly, maintenance and utility of large cassette arrays in
      prokaryote populations.

PMID- 20698954
TI  - Prognostic significance of lymphangiogenesis in pharyngolaryngeal carcinoma
      patients.
AB  - BACKGROUND: Lymphatic vessel spread is considered a major route for head and neck
      squamous cell carcinoma metastasis. Formation of new lymphatic vessels could
      facilitate the process, raising the malignant potential of these tumours. Recent
      identification of lymphatic markers allows the study of the lymphangiogenesis
      phenomenon. We searched for molecular events involved in the lymphangiogenic
      process that could have prognostic value in laryngeal/pharyngeal carcinoma
      patients. METHODS: 104 paraffin-embedded pharyngeal/laryngeal tumour samples were
      studied. Immunohistochemical analysis of podoplanin and double immunofluorescence
      analysis of Ki-67 and D2-40 were performed. Lymph vessel density (inside the
      tumour mass, at its periphery or considered as a whole) and the presence of
      tumour emboli inside lymphatics were recorded. The proliferative state of
      endothelial lymphatic cells was evaluated. RESULTS: Lymphatic vessels were
      detected inside the tumour mass (75%) and in the surrounding tissue (80%); some
      of them in a proliferative state. Tumour emboli were detected in a high
      proportion of the cases (45%). Lymphatic vessel density was higher in the
      pharyngeal cases (p = 0.0029), in greater size (p = 0.039), more advanced stage
      primary tumours (p = 0.006) and in carcinomas of patients with affected nodes (p
      = 0.019). The presence of tumour emboli and a high global vessel density were
      indicators of poor prognosis (recorded as death from tumour) in the laryngeal
      group (p = 0.015 and p = 0.027, respectively), but notably not in the pharyngeal
      one. Interestingly, high global vessel density showed a negative prognostic value
      among pathologically staged N0 laryngeal carcinomas (p = 0.03). CONCLUSIONS: The
      lymphangiogenic process correlated with aggressive tumour features (pN category,
      tumour size, tumour stage), but might play different roles in tumours arising
      from different anatomic sites. Our results suggest that detection of tumour
      emboli and assessment of global vessel density using the D2-40 antibody, may be
      useful in the clinical practice, as predictors of reduced survival among pN0
      laryngeal carcinoma patients.

PMID- 20698955
TI  - Achievements and challenges in bioartificial kidney development.
AB  - Bioartificial kidneys (BAKs) combine a conventional hemofilter in series with a
      bioreactor unit containing renal epithelial cells. The epithelial cells derived
      from the renal tubule should provide transport, metabolic, endocrinologic and
      immunomodulatory functions. Currently, primary human renal proximal tubule cells
      are most relevant for clinical applications. However, the use of human primary
      cells is associated with many obstacles, and the development of alternatives and
      an unlimited cell source is one of the most urgent challenges. BAKs have been
      applied in Phase I/II and Phase II clinical trials for the treatment of
      critically ill patients with acute renal failure. Significant effects on cytokine
      concentrations and long-term survival were observed. A subsequent Phase IIb
      clinical trial was discontinued after an interim analysis, and these results
      showed that further intense research on BAK-based therapies for acute renal
      failure was required. Development of BAK-based therapies for the treatment of
      patients suffering from end-stage renal disease is even more challenging, and
      related problems and research approaches are discussed herein, along with the
      development of mobile, portable, wearable and implantable devices.

PMID- 20698957
TI  - First nationwide survey on cardiovascular risk factors in Grand-Duchy of
      Luxembourg (ORISCAV-LUX).
AB  - BACKGROUND: The ORISCAV-LUX study is the first baseline survey of an on-going
      cardiovascular health monitoring programme in Grand-Duchy of Luxembourg. The main
      objectives of the present manuscript were 1) to describe the study design and
      conduct, and 2) to present the salient outcomes of the study, in particular the
      prevalence of the potentially modifiable and treatable cardiovascular disease
      risk factors in the adult population residing in Luxembourg. METHOD: ORISCAV-LUX
      is a cross-sectional study based on a random sample of 4496 subjects, stratified
      by gender, age categories and district, drawn from the national insurance
      registry of 18-69 years aged Luxembourg residents, assuming a response rate of
      30% and a proportion of 5% of institutionalized subjects in each stratum. The
      cardiovascular health status was assessed by means of a self-administered
      questionnaire, clinical and anthropometric measures, as well as by blood, urine
      and hair examinations. The potentially modifiable and treatable risk factors
      studied included smoking, hypertension, dyslipidemia, diabetes mellitus, and
      obesity. Both univariate and multivariate statistical analyses used weighted
      methods to account for the stratified sampling scheme. RESULTS: A total of 1432
      subjects took part in the survey, yielding a participation rate of 32.2%. This
      figure is higher than the minimal sample size of 1285 subjects as estimated by
      power calculation. The most predominant cardiovascular risk factors were
      dyslipidemia (69.9%), hypertension (34.5%), smoking (22.3%), and obesity (20.9%),
      while diabetes amounted 4.4%. All prevalence rates increased with age (except
      smoking) with marked gender differences (except diabetes). There was a
      significant difference in the prevalence of hypertension and of lipid disorders
      by geographic region of birth. The proportion of subjects cumulating two or more
      cardiovascular risk factors increased remarkably with age and was more
      predominant in men than in women (P<0.0001). Only 14.7% of men and 23.1% of women
      were free of any cardiovascular risk factor. High prevalence of non-treated CVRF,
      notably for hypertension and dyslipidemia, were observed in the study population.
      CONCLUSION: The population-based ORISCAV-LUX survey revealed a high prevalence of
      potentially modifiable and treatable cardiovascular risk factors among apparently
      healthy subjects; significant gender and age-specific differences were seen not
      only for single but also for combined risk factors. From a public health
      perspective, these preliminary findings stress the urgent need for early routine
      health examinations, preventive interventions and lifestyle behavioural changes,
      even in young asymptomatic adults, to decrease cardiovascular morbidity and
      mortality in Luxembourg.

PMID- 20698956
TI  - Haemodynamic optimisation improves tissue microvascular flow and oxygenation
      after major surgery: a randomised controlled trial.
AB  - INTRODUCTION: Post-operative outcomes may be improved by the use of flow related
      end-points for intra-venous fluid and/or low dose inotropic therapy. The
      mechanisms underlying this benefit remain uncertain. The objective of this study
      was to assess the effects of stroke volume guided intra-venous fluid and low dose
      dopexamine on tissue microvascular flow and oxygenation and inflammatory markers
      in patients undergoing major gastrointestinal surgery. METHODS: Randomised,
      controlled, single blind study of patients admitted to a university hospital
      critical care unit following major gastrointestinal surgery. For eight hours
      after surgery, intra-venous fluid therapy was guided by measurements of central
      venous pressure (CVP group), or stroke volume (SV group). In a third group stroke
      volume guided fluid therapy was combined with dopexamine (0.5 mcg/kg/min) (SV &
      DPX group). RESULTS: 135 patients were recruited (n = 45 per group). In the SV &
      DPX group, increased global oxygen delivery was associated with improved
      sublingual (P < 0.05) and cutaneous microvascular flow (P < 0.005) (sublingual
      microscopy and laser Doppler flowmetry). Microvascular flow remained constant in
      the SV group but deteriorated in the CVP group (P < 0.05). Cutaneous tissue
      oxygen partial pressure (PtO2) (Clark electrode) improved only in the SV & DPX
      group (P < 0.001). There were no differences in serum inflammatory markers. There
      were no differences in overall complication rates between the groups although
      acute kidney injury was more frequent in the CVP group (CVP group ten patients
      (22%); pooled SV and SV & DPX groups seven patients (8%); P = 0.03) (post hoc
      analysis). CONCLUSIONS: Stroke volume guided fluid and low dose inotropic therapy
      was associated with improved global oxygen delivery, microvascular flow and
      tissue oxygenation but no differences in the inflammatory response to surgery.
      These observations may explain improved clinical outcomes associated with this
      treatment in previous trials. TRIAL REGISTRATION NUMBER: ISRCTN 94850719.

PMID- 20698958
TI  - Burden of paediatric Rotavirus Gastroenteritis (RVGE) and potential benefits of a
      universal Rotavirus vaccination programme with a pentavalent vaccine in Spain.
AB  - BACKGROUND: Rotavirus is the most common cause of gastroenteritis in young
      children worldwide. The aim of the study was to assess the health outcomes and
      the economic impact of a universal rotavirus vaccination programme with RotaTeq,
      the pentavalent rotavirus vaccine, versus no vaccination programme in Spain.
      METHODS: A birth cohort was followed up to the age of 5 using a cohort model.
      Epidemiological parameters were taken from the REVEAL study (a prospective
      epidemiological study conducted in Spain, 2004-2005) and from the literature.
      Direct and indirect costs were assessed from the national healthcare payer and
      societal perspectives by combining health care resource utilisation collected in
      REVEAL study and unit costs from official sources. RotaTeq per protocol efficacy
      data was taken from a large worldwide rotavirus clinical trial (70,000 children).
      Health outcomes included home care cases, General Practioner (GP)/Paediatrician,
      emergency department visits, hospitalisations and nosocomial infections. RESULTS:
      The model estimates that the introduction of a universal rotavirus vaccination
      programme with RotaTeq (90% coverage rate) would reduce the rotavirus
      gastroenteritis (RVGE) burden by 75% in Spain; 53,692 home care cases, 35,187
      GP/Paediatrician visits, 34,287 emergency department visits, 10,987
      hospitalisations and 2,053 nosocomial infections would be avoided. The
      introduction of RotaTeq would avoid about 76% of RVGE-related costs from both
      perspectives: euro22 million from the national health system perspective and
      euro38 million from the societal perspective. CONCLUSIONS: A rotavirus
      vaccination programme with RotaTeq would reduce significantly the important
      medical and economic burden of RVGE in Spain.

PMID- 20698959
TI  - IDOMAL: an ontology for malaria.
AB  - BACKGROUND: Ontologies are rapidly becoming a necessity for the design of
      efficient information technology tools, especially databases, because they permit
      the organization of stored data using logical rules and defined terms that are
      understood by both humans and machines. This has as consequence both an enhanced
      usage and interoperability of databases and related resources. It is hoped that
      IDOMAL, the ontology of malaria will prove a valuable instrument when implemented
      in both malaria research and control measures. METHODS: The OBOEdit2 software was
      used for the construction of the ontology. IDOMAL is based on the Basic Formal
      Ontology (BFO) and follows the rules set by the OBO Foundry consortium. RESULTS:
      The first version of the malaria ontology covers both clinical and
      epidemiological aspects of the disease, as well as disease and vector biology.
      IDOMAL is meant to later become the nucleation site for a much larger ontology of
      vector borne diseases, which will itself be an extension of a large ontology of
      infectious diseases (IDO). The latter is currently being developed in the frame
      of a large international collaborative effort. CONCLUSIONS: IDOMAL, already
      freely available in its first version, will form part of a suite of ontologies
      that will be used to drive IT tools and databases specifically constructed to
      help control malaria and, later, other vector-borne diseases. This suite already
      consists of the ontology described here as well as the one on insecticide
      resistance that has been available for some time. Additional components are being
      developed and introduced into IDOMAL.

PMID- 20698960
TI  - Modelling the ancestral sequence distribution and model frequencies in context
      dependent models for primate non-coding sequences.
AB  - BACKGROUND: Recent approaches for context-dependent evolutionary modelling assume
      that the evolution of a given site depends upon its ancestor and that ancestor's
      immediate flanking sites. Because such dependency pattern cannot be imposed on
      the root sequence, we consider the use of different orders of Markov chains to
      model dependence at the ancestral root sequence. Root distributions which are
      coupled to the context-dependent model across the underlying phylogenetic tree
      are deemed more realistic than decoupled Markov chains models, as the
      evolutionary process is responsible for shaping the composition of the ancestral
      root sequence. RESULTS: We find strong support, in terms of Bayes Factors, for
      using a second-order Markov chain at the ancestral root sequence along with a
      context-dependent model throughout the remainder of the phylogenetic tree in an
      ancestral repeats dataset, and for using a first-order Markov chain at the
      ancestral root sequence in a pseudogene dataset. Relaxing the assumption of a
      single context-independent set of independent model frequencies as presented in
      previous work, yields a further drastic increase in model fit. We show that the
      substitution rates associated with the CpG-methylation-deamination process can be
      modelled through context-dependent model frequencies and that their accuracy
      depends on the (order of the) Markov chain imposed at the ancestral root
      sequence. In addition, we provide evidence that this approach (which assumes that
      root distribution and evolutionary model are decoupled) outperforms an approach
      inspired by the work of Arndt et al., where the root distribution is coupled to
      the evolutionary model. We show that the continuous-time approximation of Hwang
      and Green has stronger support in terms of Bayes Factors, but the parameter
      estimates show minimal differences. CONCLUSIONS: We show that the combination of
      a dependency scheme at the ancestral root sequence and a context-dependent
      evolutionary model across the remainder of the tree allows for accurate
      estimation of the model's parameters. The different assumptions tested in this
      manuscript clearly show that designing accurate context-dependent models is a
      complex process, with many different assumptions that require validation.
      Further, these assumptions are shown to change across different datasets, making
      the search for an adequate model for a given dataset quite challenging.

PMID- 20698961
TI  - Microarray meta-analysis database (M(2)DB): a uniformly pre-processed, quality
      controlled, and manually curated human clinical microarray database.
AB  - BACKGROUND: Over the past decade, gene expression microarray studies have greatly
      expanded our knowledge of genetic mechanisms of human diseases. Meta-analysis of
      substantial amounts of accumulated data, by integrating valuable information from
      multiple studies, is becoming more important in microarray research. However,
      collecting data of special interest from public microarray repositories often
      present major practical problems. Moreover, including low-quality data may
      significantly reduce meta-analysis efficiency. RESULTS: M2DB is a human curated
      microarray database designed for easy querying, based on clinical information and
      for interactive retrieval of either raw or uniformly pre-processed data, along
      with a set of quality-control metrics. The database contains more than 10,000
      previously published Affymetrix GeneChip arrays, performed using human clinical
      specimens. M2DB allows online querying according to a flexible combination of
      five clinical annotations describing disease state and sampling location. These
      annotations were manually curated by controlled vocabularies, based on
      information obtained from GEO, ArrayExpress, and published papers. For array
      based assessment control, the online query provides sets of QC metrics, generated
      using three available QC algorithms. Arrays with poor data quality can easily be
      excluded from the query interface. The query provides values from two algorithms
      for gene-based filtering, and raw data and three kinds of pre-processed data for
      downloading. CONCLUSION: M2DB utilizes a user-friendly interface for QC
      parameters, sample clinical annotations, and data formats to help users obtain
      clinical metadata. This database provides a lower entry threshold and an
      integrated process of meta-analysis. We hope that this research will promote
      further evolution of microarray meta-analysis.

PMID- 20698962
TI  - Design of an internet-based health economic evaluation of a preventive group
      intervention for children of parents with mental illness or substance use
      disorders.
AB  - BACKGROUND: Preventive interventions are developed for children of parents with
      mental and substance use disorders (COPMI), because these children have a higher
      risk of developing a psychological or behavioral disorder in the future. Mental
      health and substance use disorders contribute significantly to the global burden
      of disease. Although the exact number of parents with a mental illness is
      unclear, the subject of mentally ill parents is gaining attention. Moreover there
      is a lack of interventions for COPMI-children, as well of (cost-) effectiveness
      studies evaluating COPMI interventions. Innovative interventions such as e-health
      provide a new field for exploration. There is no knowledge about the
      opportunities for using the internet to prevent problems in children at risk. In
      the current study we will focus on the (cost-) effectiveness of an online health
      prevention program for COPMI-children. METHODS/DESIGN: We designed a randomized
      controlled trial to examine the (cost-) effectiveness of the Kopstoring
      intervention. Kopstoring is an online intervention for COPMI-children to
      strengthen their coping skills and prevent behavioral and psychological problems.
      We will compare the Kopstoring intervention with (waiting list) care as usual.
      This trial will be conducted entirely over the internet. An economic evaluation,
      from a societal perspective will be conducted, to examine the trial's cost
      effectiveness. Power calculations show that 214 participants are needed, aged 16
      25. Possible participants will be recruited via media announcements and banners
      on the internet. After screening and completing informed consent procedures,
      participants will be randomized. The main outcome is internalizing and
      externalizing symptoms as measured by the Youth Self Report. For the economic
      evaluation, healthcare costs and costs outside the healthcare sector will be
      measured at the same time as the clinical measures, at baseline, 3, 6 and 9
      months. An extended measure for the intervention group will be provided at 12
      months, to examine the long-term effects. In addition, a process evaluation will
      be conducted. DISCUSSION: Recent developments, such as international conferences
      and policy discussions, show the pressing need to study the (cost-) effectiveness
      of interventions for vulnerable groups of children. This study will shed light on
      the (cost-) effectiveness of an online preventive intervention. TRIAL
      REGISTRATION: NTR1982.

PMID- 20698963
TI  - Long-term health-related and economic consequences of short-term outcomes in
      evaluation of perinatal interventions.
AB  - BACKGROUND: Many perinatal interventions are performed to improve long-term
      neonatal outcome. To evaluate the long-term effect of a perinatal intervention
      follow-up of the child after discharge from the hospital is necessary because
      serious sequelae from perinatal complications frequently manifest themselves only
      after several years. However, long-term follow-up is time-consuming, is not in
      the awareness of obstetricians, is expensive and falls outside the funding-period
      of most obstetric studies. Consequently, short-term outcomes are often reported
      instead of the primary long-term end-point. With this project, we will assess the
      current state of affairs concerning follow-up after obstetric RCTs and we will
      develop multivariable prediction models for different long-term health outcomes.
      Furthermore, we would like to encourage other researchers participating in follow
      up studies after large obstetric trials (> 350 women) to inform us about their
      studies so that we can include their follow-up study in our systematic review. We
      would invite these researchers also to join our effort and to collaborate with us
      on the external validation of our prediction models. METHODS/DESIGN: A systematic
      review of neonatal follow-up after obstetric studies will be performed. All
      reviews of the Cochrane Pregnancy and Childbirth group will be assessed for
      reviews on interventions that aimed to improve neonatal outcome. Reviews on
      interventions primary looking at other aspects than neonatal outcome such as
      labour progress will also be included when these interventions can change the
      outcome of the neonate on the short or long-term. Our review will be limited to
      RCTs with more than 350 women. Information that will be extracted from these RCTs
      will address whether, how and for how long follow-up has been performed. However,
      in many cases long-term follow-up of the infants will not be feasible. An
      alternative solution to limited follow-up could be to develop prediction models
      to estimate long-term health outcomes of the newborn based on specific perinatal
      outcomes and other covariates. For the development of multivariable prediction
      models for several health outcomes, we will use data available from a Dutch
      cohort study of preterm (< 32 weeks) and/or small for gestational age infants (<
      1500 g). These infants were born in The Netherlands in 1983 and followed until
      they reached the age of 19. DISCUSSION: The systematic review will provide
      insight in the extent and methods used for follow-up assessments after obstetric
      RCTs in the past. The prediction models can be used by future studies to
      extrapolate short-term outcomes to a long-term horizon or to indicate for which
      neonates long-term follow-up is required, as their outcomes (either absence or
      presence of sequelae) cannot be adequately predicted from short-term outcomes and
      clinical background characteristics.

PMID- 20698964
TI  - Results of a pilot study on the involvement of bilateral inferior frontal gyri in
      emotional prosody perception: an rTMS study.
AB  - BACKGROUND: The right hemisphere may play an important role in paralinguistic
      features such as the emotional melody in speech. The extent of this involvement
      however is unclear. Imaging studies have shown involvement of both left and right
      inferior frontal gyri in emotional prosody perception. The present pilot study
      examined whether these brain areas are critically involved in the processing of
      emotional prosody and of semantics in 9 healthy subjects. Repetitive transcranial
      magnetic stimulation was used with a coil centred over left and right inferior
      frontal gyri, as localized by neuronavigation based on the subject's MRI. A sham
      condition was included. An online-TMS approach was applied; an emotional language
      task was completed during stimulation. This computerized task consisted of
      sentences pronounced by actors. In the semantics condition an emotion (fear,
      anger or neutral) was expressed in the content pronounced with a neutral
      intonation. In the prosody condition the emotion was expressed in the intonation,
      while the content was neutral. RESULTS: Reaction times on the emotional prosody
      task condition were significantly longer after rTMS over both the right and the
      left inferior frontal gyrus as compared to sham stimulation and after controlling
      for learning effects associated with order of condition. When taking all emotions
      together, there was no difference in effect on reaction times between the right
      and left stimulation. For the emotion Fear, reaction times were significantly
      longer after stimulating the left inferior frontal gyrus as compared to the right
      inferior frontal gyrus. Reaction times in the semantics task condition were not
      significantly different between the three TMS conditions. CONCLUSIONS: The data
      indicate a critical involvement of both the right and the left inferior frontal
      gyrus in emotional prosody perception. The findings of this pilot study need
      replication. Future studies should include more subjects and examine whether the
      left and right inferior frontal gyrus play a differential role and complement
      each other, e.g. in the integrated processing of linguistic and prosodic aspects
      of speech, respectively.

PMID- 20698965
TI  - Hospital safety culture in Taiwan: a nationwide survey using Chinese version
      Safety Attitude Questionnaire.
AB  - BACKGROUND: Safety activities have been initiated at many hospitals in Taiwan,
      but little is known about the safety culture at these hospitals. The aims of this
      study were to verify a safety culture survey instrument in Chinese and to assess
      hospital safety culture in Taiwan. METHODS: The Taiwan Patient Safety Culture
      Survey was conducted in 2008, using the adapted Safety Attitude Questionnaire in
      Chinese (SAQ-C). Hospitals and their healthcare workers participated in the
      survey on a voluntary basis. The psychometric properties of the five SAQ-C
      dimensions were examined, including teamwork climate, safety climate, job
      satisfaction, perception of management, and working conditions. Additional safety
      measures were asked to assess healthcare workers' attitudes toward their
      collaboration with nurses, physicians, and pharmacists, respectively, and
      perceptions of hospitals' encouragement of safety reporting, safety training, and
      delivery delays due to communication breakdowns in clinical areas. The
      associations between the respondents' attitudes to each SAQ-C dimension and
      safety measures were analyzed by generalized estimating equations, adjusting for
      the clustering effects at hospital levels. RESULTS: A total of 45,242 valid
      questionnaires were returned from 200 hospitals with a mean response rate of
      69.4%. The Cronbach's alpha was 0.792 for teamwork climate, 0.816 for safety
      climate, 0.912 for job satisfaction, 0.874 for perception of management, and
      0.785 for working conditions. Confirmatory factor analyses demonstrated a good
      model fit for each dimension and the entire construct. The percentage of hospital
      healthcare workers holding positive attitude was 48.9% for teamwork climate,
      45.2% for perception of management, 42.1% for job satisfaction, 37.2% for safety
      climate, and 31.8% for working conditions. There were wide variations in the
      range of SAQ-C scores in each dimension among hospitals. Compared to those
      without positive attitudes, healthcare workers with positive attitudes to each
      SAQ dimension were more likely to perceive good collaboration with coworkers, and
      their hospitals were more likely to encourage safety reporting and to prioritize
      safety training programs (Wald chi-square test, p < 0.001 for all). CONCLUSIONS:
      Analytical results verified the psychometric properties of the SAQ-C at Taiwanese
      hospitals. The safety culture at most hospitals has not fully developed and there
      is considerable room for improvement.

PMID- 20698967
TI  - Socioeconomic status and self-reported asthma in Indigenous and non-Indigenous
      Australian adults aged 18-64 years: analysis of national survey data.
AB  - BACKGROUND: Asthma is more common among Indigenous than non-Indigenous Australian
      adults, but little is known about socioeconomic patterning of asthma within the
      Indigenous population, or whether it is similar to the non-Indigenous population.
      METHODS: I analysed weighted data on self-reported current diagnosed asthma and a
      range of socio-economic and demographic measures for 5,417 Indigenous and 15,432
      non-Indigenous adults aged 18-64 years from two nationally representative surveys
      conducted in parallel by the Australian Bureau of Statistics in 2004-05. RESULTS:
      Current asthma prevalence was higher for Indigenous than non-Indigenous people in
      every age group. After adjusting for age and sex, main language and place of
      residence were significantly associated with asthma prevalence in both
      populations. Traditional SES variables such as education, income and employment
      status were significantly associated with asthma in the non-Indigenous but not
      the Indigenous population. For example, age-and sex-adjusted relative odds of
      asthma among those who did not complete Year 10 (versus those who did) was 1.2
      (95% confidence interval (CI) 1.0-1.5) in the non-Indigenous population versus
      1.0 (95% CI 0.8-1.3) in the Indigenous population. CONCLUSIONS: The socioeconomic
      patterning of asthma among Indigenous Australians is much less pronounced than
      for other chronic diseases such as diabetes and kidney disease, and contrasts
      with asthma patterns in the non-Indigenous population. This may be due in part to
      the episodic nature of asthma, and the well-known challenges in diagnosing it,
      especially among people with limited health literacy and/or limited access to
      health care, both of which are more likely in the Indigenous population. It may
      also reflect the importance of exposures occurring across the socioeconomic
      spectrum among Indigenous Australians, such as racism, and discrimination,
      marginalization and dispossession, chronic stress and exposure to violence.

PMID- 20698966
TI  - Sepsis is a major determinant of outcome in critically ill HIV/AIDS patients.
AB  - INTRODUCTION: New challenges have arisen for the management of critically ill
      HIV/AIDS patients. Severe sepsis has emerged as a common cause of intensive care
      unit (ICU) admission for those living with HIV/AIDS. Contrastingly, HIV/AIDS
      patients have been systematically excluded from sepsis studies, limiting the
      understanding of the impact of sepsis in this population. We prospectively
      followed up critically ill HIV/AIDS patients to evaluate the main risk factors
      for hospital mortality and the impact of severe sepsis on the short- and long
      term survival. METHODS: All consecutive HIV-infected patients admitted to the ICU
      of an infectious diseases research center, from June 2006 to May 2008, were
      included. Severity of illness, time since AIDS diagnosis, CD4 cell count,
      antiretroviral treatment, incidence of severe sepsis, and organ dysfunctions were
      registered. The 28-day, hospital, and 6-month outcomes were obtained for all
      patients. Cox proportional hazards regression analysis measured the effect of
      potential factors on 28-day and 6-month mortality. RESULTS: During the 2-year
      study period, 88 HIV/AIDS critically ill patients were admitted to the ICU.
      Seventy percent of patients had opportunist infections, median CD4 count was 75
      cells/mm3, and 45% were receiving antiretroviral therapy. Location on a ward
      before ICU admission, cardiovascular and respiratory dysfunctions on the first
      day after admission, and the presence of severe sepsis/septic shock were
      associated with reduced 28-day and 6-month survival on a univariate analysis.
      After a multivariate analysis, severe sepsis determined the highest hazard ratio
      (HR) for 28-day (adjusted HR, 3.13; 95% CI, 1.21-8.07) and 6-month (adjusted HR,
      3.35; 95% CI, 1.42-7.86) mortality. Severe sepsis occurred in 44 (50%) patients,
      mainly because of lower respiratory tract infections. The survival of septic and
      nonseptic patients was significantly different at 28-day and 6-month follow-up
      times (log-rank and Peto test, P < 0.001). CONCLUSIONS: Severe sepsis has emerged
      as a major cause of admission and mortality for hospitalized HIV/AIDS patients,
      significantly affecting short- and longer-term survival of critically ill
      HIV/AIDS patients.

PMID- 20698968
TI  - A complete DNA sequence map of the ovine major histocompatibility complex.
AB  - BACKGROUND: The ovine Major Histocompatibility Complex (MHC) harbors clusters of
      genes involved in overall resistance/susceptibility of an animal to infectious
      pathogens. However, only a limited number of ovine MHC genes have been identified
      and no adequate sequence information is available, as compared to those of swine
      and bovine. We previously constructed a BAC clone-based physical map that covers
      entire class I, class II and class III region of ovine MHC. Here we describe the
      assembling of a complete DNA sequence map for the ovine MHC by shotgun sequencing
      of 26 overlapping BAC clones. RESULTS: DNA shotgun sequencing generated
      approximately 8-fold genome equivalent data that were successfully assembled into
      a finished sequence map of the ovine MHC. The sequence map spans approximately
      2,434,000 nucleotides in length, covering almost all of the MHC loci currently
      known in the sheep and cattle. Gene annotation resulted in the identification of
      177 protein-coding genes/ORFs, among which 145 were not previously reported in
      the sheep, and 10 were ovine species specific, absent in cattle or other mammals.
      A comparative sequence analyses among human, sheep and cattle revealed a high
      conservation in the MHC structure and loci order except for the class II, which
      were divided into IIa and IIb subregions in the sheep and cattle, separated by a
      large piece of non-MHC autosome of approximately 18.5 Mb. In addition, a total of
      18 non-protein-coding microRNAs were predicted in the ovine MHC region for the
      first time. CONCLUSION: An ovine MHC DNA sequence map was successfully assembled
      by shotgun sequencing of 26 overlapping BAC clone. This makes the sheep the
      second ruminant species for which the complete MHC sequence information is
      available for evolution and functional studies, following that of the bovine. The
      results of the comparative analysis support a hypothesis that an inversion of the
      ancestral chromosome containing the MHC has shaped the MHC structures of
      ruminants, as we currently observed in the sheep and cattle. Identification of
      relative large numbers of microRNAs in the ovine MHC region helps to provide
      evidence that microRNAs are actively involved in the regulation of MHC gene
      expression and function.

PMID- 20698969
TI  - Clinical and histologic features of botryoid odontogenic cyst: a case report.
AB  - INTRODUCTION: The lateral periodontal cyst, as the name implies, occurs on a
      lateral periodontal location and is of developmental origin, arising from cystic
      degeneration of clear cells of the dental lamina. A botryoid odontogenic cyst is
      considered to be a rare multilocular variant of a lateral periodontal cyst. CASE
      PRESENTATION: We report the clinical and histopathologic features of a rare case
      of botryoid odontogenic cyst found in an edentulous area corresponding to the
      right lower canine of a 64-year-old African-American woman. A multilocular
      radiolucency was observed, and surgical removal of the lesion revealed a nodule
      of rubber-like consistency measuring about 1.5 cm in diameter. Cross-sectioning
      of the nodule showed that it consisted of various cystic compartments.
      Histologically, various voluminous periodic acid-Schiff-negative clear cells
      randomly distributed throughout the cystic epithelium were observed, as well as
      cell layers showing thickenings generally formed by oval, sometimes entangled
      plaques. The capsule consisted of fibrous connective tissue and showed rare and
      discrete foci of a perivascular mononuclear inflammatory infiltrate and reactive
      bone-tissue fragments. The final diagnosis was botryoid odontogenic cyst.
      CONCLUSION: We provide data that allow the reader to establish the differences
      between botryoid odontogenic cyst, glandular odontogenic cyst, and lateral
      periodontal cyst, helping with the differential diagnosis. The reader will have
      the opportunity to review botryoid odontogenic cyst clinical and histopathologic
      features, including treatment.

PMID- 20698970
TI  - Oligomerization of Uukuniemi virus nucleocapsid protein.
AB  - BACKGROUND: Uukuniemi virus (UUKV) belongs to the Phlebovirus genus in the family
      Bunyaviridae. As a non-pathogenic virus for humans UUKV has served as a safe
      model bunyavirus in a number of studies addressing fundamental questions such as
      organization and regulation of viral genes, genome replication, structure and
      assembly. The present study is focused on the oligomerization of the UUKV
      nucleocapsid (N) protein, which plays an important role in several steps of virus
      replication. The aim was to locate the domains involved in the N protein
      oligomerization and study the process in detail. RESULTS: A set of experiments
      concentrating on the N- and C-termini of the protein was performed, first by
      completely or partially deleting putative N-N-interaction domains and then by
      introducing point mutations of amino acid residues. Mutagenesis strategy was
      based on the computer modeling of secondary and tertiary structure of the N
      protein. The N protein mutants were studied in chemical cross-linking,
      immunofluorescence, mammalian two-hybrid, minigenome, and virus-like particle
      forming assays. The data showed that the oligomerization ability of UUKV-N
      protein depends on the presence of intact alpha-helices on both termini of the N
      protein molecule and that a specific structure in the N-terminal region plays a
      crucial role in the N-N interaction(s). This structure is formed by two alpha
      helices, rich in amino acid residues with aromatic (W7, F10, W19, F27, F31) or
      long aliphatic (I14, I24) side chains. Furthermore, some of the N-terminal
      mutations (e.g. I14A, I24A, F31A) affected the N protein functionality both in
      mammalian two-hybrid and minigenome assays. CONCLUSIONS: UUKV-N protein has
      ability to form oligomers in chemical cross-linking and mammalian two-hybrid
      assays. In mutational analysis, some of the introduced single-point mutations
      abolished the N protein functionality both in mammalian two-hybrid and minigenome
      assays, suggesting that especially the N-terminal region of the UUKV-N protein is
      essential for the N-N interaction.

PMID- 20698971
TI  - Acute liver failure following hemodialysis arteriovenous graft placement: a case
      report.
AB  - INTRODUCTION: Severe high-output cardiac failure is a serious complication of
      high-flow vascular access requiring immediate intervention. Ischemic hepatitis is
      defined as a massive increase in serum transaminase levels due to an imbalance
      between hepatic oxygen supply and demand in the absence of other acute causes of
      liver damage. It is typically preceded by hypotension, hypoxemia, or both, and
      occurs mostly in elderly patients with right-sided congestive heart failure. CASE
      PRESENTATION: We report a fatal case of acute liver failure in an 84-year-old
      Caucasian man with high-output cardiac failure due to arteriovenous hemodialysis
      access. The chronological sequence of acute liver failure in the context of
      vascular access created two days before suggests that ischemic hepatitis was the
      result of high-output cardiac failure due to vascular access. CONCLUSIONS: A
      thorough cardiac assessment should be performed in patients with severe cardiac
      disease prior to placing an arteriovenous access, and arteriovenous fistula
      should be the preferred vascular access.

PMID- 20698972
TI  - Mating system drives negative associations between morphological features in
      Schistosomatidae.
AB  - BACKGROUND: Sexual morphological features are known to be associated with the
      mating systems of several animal groups. However, it has been suggested that
      morphological features other than sexual characteristics could also be
      constrained by the mating system as a consequence of negative associations.
      Schistosomatidae are parasitic organisms that vary in mating system and can thus
      be used to explore links between the mating system and negative associations with
      morphological features. RESULTS: A comparative analysis of Schistosomatidae
      morphological features revealed an association between the mating system
      (monogamous versus polygynandrous) and morphological characteristics of
      reproduction, nutrition, and locomotion. CONCLUSIONS: The mating system drives
      negative associations between somatic and sexual morphological features. In
      monogamous species, males display a lower investment in sexual tissues and a
      higher commitment of resources to tissues involved in female transport,
      protection, and feeding assistance. In contrast, males of polygynandrous species
      invest to a greater extent in sexual tissues at the cost of reduced commitment to
      female care.

PMID- 20698973
TI  - Nonpreserved amniotic membrane transplantation for bilateral toxic keratopathy
      caused by topical anesthetic abuse: a case report.
AB  - INTRODUCTION: Corneal damage associated with abuse of topical anesthetics is a
      rare clinic entity. Topical anesthetic abuse is one of the causes of ring
      keratitis. Ring keratitis is easily overlooked because it can mimic acanthamoeba
      keratitis or other infectious keratitis. The outcome is often poor, leading to
      persistent epithelial defects, corneal scarring, and perforations. CASE
      PRESENTATION: We report the clinical presentation, diagnosis, and treatment of a
      65-year-old Caucasian man, who worked as a health care worker, with bilateral
      toxic keratopathy caused by topical anesthetic abuse. Nonpreserved amniotic
      membrane transplantation was performed for both eyes of the patient. CONCLUSION:
      It is important to identify and treat patients who abuse topical anesthetics
      before permanent vision loss ensues. Nonpreserved amniotic membrane
      transplantation may be useful in relieving pain and improving corneal surface in
      anesthetic agent abusers.

PMID- 20698974
TI  - Microsatellite-based genetic diversity and population structure of domestic sheep
      in northern Eurasia.
AB  - BACKGROUND: Identification of global livestock diversity hotspots and their
      importance in diversity maintenance is essential for making global conservation
      efforts. We screened 52 sheep breeds from the Eurasian subcontinent with 20
      microsatellite markers. By estimating and weighting differently within- and
      between-breed genetic variation our aims were to identify genetic diversity
      hotspots and prioritize the importance of each breed for conservation,
      respectively. In addition we estimated how important within-species diversity
      hotspots are in livestock conservation. RESULTS: Bayesian clustering analysis
      revealed three genetic clusters, termed Nordic, Composite and Fat-tailed.
      Southern breeds from close to the region of sheep domestication were more
      variable, but less genetically differentiated compared with more northern
      populations. Decreasing weight for within-breed diversity component led to very
      high representation of genetic clusters or regions containing more diverged
      breeds, but did not increase phenotypic diversity among the high ranked breeds.
      Sampling populations throughout 14 regional groups was suggested for maximized
      total genetic diversity. CONCLUSIONS: During initial steps of establishing a
      livestock conservation program populations from the diversity hot-spot area are
      the most important ones, but for the full design our results suggested that
      approximately equal population presentation across environments should be
      considered. Even in this case, higher per population emphasis in areas of high
      diversity is appropriate. The analysis was based on neutral data, but we have no
      reason to think the general trend is limited to this type of data. However, a
      comprehensive valuation of populations should balance production systems,
      phenotypic traits and available genetic information, and include consideration of
      probability of success.

PMID- 20698976
TI  - Bilateral temporomandibular joint dislocation in a 29-year-old man: a case
      report.
AB  - INTRODUCTION: A dislocation of the temporomandibular joint represents three
      percent of all reported dislocated joints.The treatment entails reduction of the
      deformity and this can often be achieved in a ward setting. CASE PRESENTATION: We
      present the case of a 29-year-old Caucasian man with a non-traumatic bilateral
      anterior temporomandibular joint dislocation. Following several unsuccessful
      attempts, due to both inadequate patient analgesia and sedation, joint reduction
      had to be performed in theatre with the patient under general anesthesia.
      CONCLUSION: This case highlights the importance of providing the patient with
      adequate analgesia and sedation when attempting the reduction of
      temporomandibular joint dislocations.

PMID- 20698975
TI  - Asthma-susceptibility variants identified using probands in case-control and
      family-based analyses.
AB  - BACKGROUND: Asthma is a chronic respiratory disease whose genetic basis has been
      explored for over two decades, most recently via genome-wide association studies.
      We sought to find asthma-susceptibility variants by using probands from a single
      population in both family-based and case-control association designs. METHODS: We
      used probands from the Childhood Asthma Management Program (CAMP) in two primary
      genome-wide association study designs: (1) probands were combined with publicly
      available population controls in a case-control design, and (2) probands and
      their parents were used in a family-based design. We followed a two-stage
      replication process utilizing three independent populations to validate our
      primary findings. RESULTS: We found that single nucleotide polymorphisms with
      similar case-control and family-based association results were more likely to
      replicate in the independent populations, than those with the smallest p-values
      in either the case-control or family-based design alone. The single nucleotide
      polymorphism that showed the strongest evidence for association to asthma was
      rs17572584, which replicated in 2/3 independent populations with an overall p
      value among replication populations of 3.5E-05. This variant is near a gene that
      encodes an enzyme that has been implicated to act coordinately with modulators of
      Th2 cell differentiation and is expressed in human lung. CONCLUSIONS: Our results
      suggest that using probands from family-based studies in case-control designs,
      and combining results of both family-based and case-control approaches, may be a
      way to augment our ability to find SNPs associated with asthma and other complex
      diseases.

PMID- 20698977
TI  - Predictors of mortality of patients newly diagnosed with clinical type 2
      diabetes: a 5-year follow up study.
AB  - BACKGROUND: At diabetes diagnosis major decisions about life-style changes and
      treatments are made based on characteristics measured shortly after diagnosis.
      The predictive value for mortality of these early characteristics is widely
      unknown. We examined the predictive value of patient characteristics measured
      shortly after diabetes diagnosis for 5-year all-cause and cardiovascular
      mortality with special reference to self-rated general health. METHODS: Data were
      from a population-based sample of 1,323 persons newly diagnosed with clinical
      diabetes and aged 40 years or over. Possible predictors of mortality were
      investigated in Cox regression models. RESULTS: Multivariately patients who rated
      their health less than excellent experienced increased all-cause and
      cardiovascular mortality. These end-points also increased with sedentary life
      style, relatively young age at diagnosis and presence of cardiovascular disease
      (CVD) at diagnosis. Further predictors of all-cause mortality were male sex, low
      body mass index and cancer, while cardiovascular mortality increased with urinary
      albumin concentration. CONCLUSIONS: We found that patients who rated their health
      as less than excellent had increased 5-year mortality, similar to that of
      patients with prevalent CVD, even when biochemical, clinical and life-style
      variables were controlled for. This finding could motivate doctors to discuss
      perceptions of health with newly diagnosed diabetic patients and be attentive to
      patients with suboptimal health ratings. Our findings also confirm that life
      style changes and optimizing treatment are particularly relevant for relatively
      young and inactive patients and those who already have CVD or (micro)albuminuria
      at the time of diabetes diagnosis.

PMID- 20698978
TI  - Factors associated with pastoral community knowledge and occurrence of
      mycobacterial infections in human-animal interface areas of Nakasongola and
      Mubende districts, Uganda.
AB  - BACKGROUND: Nontuberculous mycobacteria (NTM) are emerging opportunistic
      pathogens whose role in human and animal disease is increasingly being
      recognized. Major concerns are their role as opportunistic pathogens in HIV/AIDS
      infections. The role of open natural water sources as source and
      livestock/wildlife as reservoirs of infections to man are well documented. This
      presents a health challenge to the pastoral systems in Africa that rely mostly on
      open natural water sources to meet livestock and human needs. Recent study in the
      pastoral areas of Uganda showed infections with same genotypes of NTM in
      pastoralists and their livestock. The aim of this study was to determine the
      environmental, animal husbandry and socio-demographic factors associated with
      occurrence and the pastoral community knowledge of mycobacterial infections at
      the human-environment-livestock/wildlife interface (HELI) areas in pastoral
      ecosystems of Uganda. METHODS: Two hundred and fifty three (253) individuals were
      subjected to a questionnaire survey across the study districts of Nakasongola and
      Mubende. Data were analyzed using descriptive statistics and multivariable
      logistic regression analysis. RESULTS: Humans sharing of the water sources with
      wild animals from the forest compared to savannah ecosystem (OR = 3.3), the tribe
      of herding pastoral community (OR = 7.9), number of rooms present in household (3
      5 vs. 1-2 rooms) (OR = 3.3) were the socio-demographic factors that influenced
      the level of knowledge on mycobacterial infections among the pastoral
      communities. Tribe (OR = 6.4), use of spring vs. stream water for domestic use
      (OR = 4.5), presence of sediments in household water receptacle (OR = 2.32), non
      separation of water containers for drinking and domestic use (OR = 2.46), sharing
      of drinking water sources with wild animals (OR = 2.1), duration of involvement
      of >5 yrs in cattle keeping (OR = 3.7) and distance of household to animal night
      shelters (>20 meters) (OR = 3.8) were significant socio-demographic factors
      associated with the risk of occurrence of mycobacterioses among the pastoral
      communities in Uganda. CONCLUSION: The socio-demographic, environmental and
      household related factors influence the risk of occurrence as well as
      pastoralists' knowledge of mycobacterial infections in the pastoral households at
      the human-environment-livestock/wildlife pastoral interface areas of Uganda.

PMID- 20698979
TI  - High risk behavior for HIV transmission among former injecting drug users: a
      survey from Indonesia.
AB  - BACKGROUND: Injecting drug use is an increasingly important cause of HIV
      transmission in most countries worldwide, especially in eastern Europe, South
      America, and east and southeast Asia. Among people actively injecting drugs,
      provision of clean needles and opioid substitution reduce HIV-transmission.
      However, former injecting drug users (fIDUs) are often overlooked as a high risk
      group for HIV transmission. We compared HIV risk behavior among current and
      former injecting drug users (IDUs) in Indonesia, which has a rapidly growing HIV
      epidemic largely driven by injecting drug use. METHODS: Current and former IDUs
      were recruited by respondent driven sampling in an urban setting in Java, and
      interviewed regarding drug use and HIV risk behavior using the European Addiction
      Severity Index and the Blood Borne Virus Transmission Questionnaire. Drug use and
      HIV transmission risk behavior were compared between current IDUs and former
      IDUs, using the Mann-Whitney and Pearson Chi-square test. RESULTS: Ninety-two out
      of 210 participants (44%) were self reported former IDUs. Risk behavior related
      to sex, tattooing or piercing was common among current as well as former IDUs,
      13% of former IDUs were still exposed to contaminated injecting equipment. HIV
      infection was high among former (66%) and current (60%) IDUs. CONCLUSION: Former
      IDUs may contribute significantly to the HIV-epidemic in Indonesia, and HIV
      prevention should therefore also target this group, addressing sexual and other
      risk behavior.

PMID- 20698980
TI  - Social deprivation and exposure to health promotion. A study of the distribution
      of health promotion resources to schools in England.
AB  - BACKGROUND: Area deprivation is a known determinant of health. It is also known
      that area deprivation is associated with lower impact health promotion. It is
      less well known, however, whether deprived areas are less responsive to health
      promotion, or whether they are less exposed. Using data from a national, school
      based campaign to promote vaccination against the human papilloma virus (HPV),
      the relationship between area deprivation and exposure was examined. METHODS:
      Taking advantage of a health promotion campaign to provide information to schools
      about HPV vaccination, a cross sectional study was conducted to examine the
      relationship between area level, social deprivation, and take-up of (i.e.,
      exposure to) available health promotion material. The sample was 4,750 schools
      across England, including government maintained and independent schools. The
      relationship between area deprivation and exposure was examined using bi- and
      multivariate logistic regression. RESULTS: It was found that schools in the least
      deprived quintile had 1.32 times the odds of requesting health promotion
      materials than schools in the most deprived areas (p = .01). This effect was
      independent of the school size, the type of school, and the geographic region.
      CONCLUSION: The relationship between area deprivation and the impact of health
      promotion may be due, at least in part, to differential levels of exposure. The
      study was limited in scope, pointing to the need for more research, but also
      points to potentially important policy implications.

PMID- 20698981
TI  - baySeq: empirical Bayesian methods for identifying differential expression in
      sequence count data.
AB  - BACKGROUND: High throughput sequencing has become an important technology for
      studying expression levels in many types of genomic, and particularly
      transcriptomic, data. One key way of analysing such data is to look for elements
      of the data which display particular patterns of differential expression in order
      to take these forward for further analysis and validation. RESULTS: We propose a
      framework for defining patterns of differential expression and develop a novel
      algorithm, baySeq, which uses an empirical Bayes approach to detect these
      patterns of differential expression within a set of sequencing samples. The
      method assumes a negative binomial distribution for the data and derives an
      empirically determined prior distribution from the entire dataset. We examine the
      performance of the method on real and simulated data. CONCLUSIONS: Our method
      performs at least as well, and often better, than existing methods for analyses
      of pairwise differential expression in both real and simulated data. When we
      compare methods for the analysis of data from experimental designs involving
      multiple sample groups, our method again shows substantial gains in performance.
      We believe that this approach thus represents an important step forward for the
      analysis of count data from sequencing experiments.

PMID- 20698982
TI  - Visual neglect in posterior cortical atrophy.
AB  - BACKGROUND: In posterior cortical atrophy (PCA), there is a progressive
      impairment of high-level visual functions and parietal damage, which might
      predict the occurrence of visual neglect. However, neglect may pass undetected if
      not assessed with specific tests, and might therefore be underestimated in PCA.
      In this prospective study, we aimed at establishing the side, the frequency and
      the severity of visual neglect, visual extinction, and primary visual field
      defects in an unselected sample of PCA patients. METHODS: Twenty-four right
      handed PCA patients underwent a standardized battery of neglect tests. Visual
      fields were examined clinically by the confrontation method. RESULTS: Sixteen of
      the 24 patients (66%) had signs of visual neglect on at least one test, and
      fourteen (58%) also had visual extinction or hemianopia. Five patients (21%) had
      neither neglect nor visual field defects. As expected, left-sided neglect was
      more severe than right-sided neglect. However, right-sided neglect resulted more
      frequently in this population (29%) than in previous studies on focal brain
      lesions. CONCLUSION: When assessed with specific visuospatial tests, visual
      neglect is frequent in patients with PCA. Diagnosis of neglect is important
      because of its negative impact on daily activities. Clinicians should consider
      the routine use of neglect tests to screen patients with high-level visual
      deficits. The relatively high frequency of right-sided neglect in
      neurodegenerative patients supports the hypothesis that bilateral brain damage is
      necessary for right-sided neglect signs to occur, perhaps because of the presence
      in the right hemisphere of crucial structures whose damage contributes to
      neglect.

PMID- 20698984
TI  - The clinical Pseudomonas fluorescens MFN1032 strain exerts a cytotoxic effect on
      epithelial intestinal cells and induces Interleukin-8 via the AP-1 signaling
      pathway.
AB  - BACKGROUND: Pseudomonas fluorescens is present in low number in the intestinal
      lumen and has been proposed to play a role in Crohn's disease (CD). Indeed, a
      highly specific antigen, I2, has been detected in CD patients and correlated to
      the severity of the disease. We aimed to determine whether P. fluorescens was
      able to adhere to human intestinal epithelial cells (IECs), induce cytotoxicity
      and activate a proinflammatory response. RESULTS: Behaviour of the clinical
      strain P. fluorescens MFN1032 was compared to that of the psychrotrophic strain
      P. fluorescens MF37 and the opportunistic pathogen P. aeruginosa PAO1. Both
      strains of P. fluorescens were found to adhere on Caco-2/TC7 and HT-29 cells.
      Their cytotoxicity towards these two cell lines determined by LDH release assays
      was dose-dependent and higher for the clinical strain MFN1032 than for MF37 but
      lower than P. aeruginosa PAO1. The two strains of P. fluorescens also induced IL
      8 secretion by Caco-2/TC7 and HT-29 cells via the AP-1 signaling pathway whereas
      P. aeruginosa PAO1 potentially used the NF-kappaB pathway. CONCLUSIONS: The
      present work shows, for the first time, that P. fluorescens MFN1032 is able to
      adhere to IECs, exert cytotoxic effects and induce a proinflammatory reaction.
      Our results are consistent with a possible contribution of P. fluorescens in CD
      and could explain the presence of specific antibodies against this bacterium in
      the blood of patients.

PMID- 20698983
TI  - Peristalsis in the junction region of the Drosophila larval midgut is modulated
      by DH31 expressing enteroendocrine cells.
AB  - BACKGROUND: The underlying cellular and molecular mechanisms that coordinate the
      physiological processes in digestion are complex, cryptic, and involve the
      integration of multiple cellular and organ systems. In all intestines,
      peristaltic action of the gut moves food through the various stages of digestion
      from the anterior end towards the posterior, with the rate of flow dependent on
      signals, both intrinsic and extrinsic to the gut itself. RESULTS: We have
      identified an enteroendocrine cell type that regulates gut motility in the
      Drosophila melanogaster larval midgut. These cells are located at the junction of
      the anterior and the acidic portions of the midgut and are a group of
      enteroendocrine cells that express the peptide hormone Diuretic Hormone 31 in
      this region of the gut. Using cell ablation and ectopic activation via expression
      of the Chlamydomonas reinhardtii blue light-activated channelopsin, we
      demonstrate that these enteroendocrine cells are both necessary and sufficient
      for the peristalsis in the junction region of the midgut and require the Diuretic
      Hormone 31 to affect normal peristalsis in this region. Within the same junction
      region of the midgut, we have also identified morphological features suggesting
      that this region acts as a valve that regulates the transit of food from the
      anterior midgut into the acidic portion of the gut. CONCLUSIONS: We have
      characterized and described a set of enteroendocrine cells called the Midgut
      Junction DH31 expressing cells that are required for peristaltic movement in the
      junction region between the anterior portion and acidic region of the larval
      midgut of Drosophila melanogaster. We have shown that the Midgut Junction DH31
      expressing cells are necessary and sufficient for motility and that the peptide
      hormone DH31 is required for peristalsis in the junction region of the midgut.
      The Drosophila model system will allow for a further dissection of the digestion
      process and provide a better understanding of the mechanisms that regulate
      digestion in all organisms.

PMID- 20698985
TI  - Restoration of radiation therapy-induced salivary gland dysfunction in mice by
      post therapy IGF-1 administration.
AB  - BACKGROUND: Radiotherapy for head and neck cancer results in severe and chronic
      salivary gland dysfunction in most individuals. This results in significant side
      effects including xerostomia, dysphagia, and malnutrition which are linked to
      significant reductions in patients' quality of life. Currently there are few
      xerostomia treatment approaches that provide long-term results without
      significant side effects. To address this problem we investigated the potential
      for post-therapeutic IGF-1 to reverse radiation-induced salivary gland
      dysfunction. METHODS: FVB mice were treated with targeted head and neck radiation
      and significant reductions in salivary function were confirmed 3 days after
      treatment. On days 4-8 after radiation, one group of mice was injected
      intravenously with IGF-1 while a second group served as a vehicle control.
      Stimulated salivary flow rates were evaluated on days 30, 60, and 90 and
      histological analysis was performed on days 9, 30, 60, and 90. RESULTS:
      Irradiated animals receiving vehicle injections have 40-50% reductions in
      stimulated salivary flow rates throughout the entire time course. Mice receiving
      injections of IGF-1 have improved stimulated salivary flow rates 30 days after
      treatment. By days 60-90, IGF-1 injected mice have restored salivary flow rates
      to unirradiated control mice levels. Parotid tissue sections were stained for
      amylase as an indicator of functioning acinar cells and significant reductions in
      total amylase area are detected in irradiated animals compared to unirradiated
      groups on all days. Post-therapeutic injections of IGF-1 results in increased
      amylase-positive acinar cell area and improved amylase secretion. Irradiated mice
      receiving IGF-1 show similar proliferation indices as untreated mice suggesting a
      return to tissue homeostasis. CONCLUSIONS: Post-therapeutic IGF-1 treatment
      restores salivary gland function potentially through normalization of cell
      proliferation and improved expression of amylase. These findings could aid in the
      rational design of therapy protocols or drugs for the treatment of radiation
      induced salivary gland dysfunction in patients who have completed their anti
      cancer therapies.

PMID- 20698986
TI  - Parthenolide induces proliferation inhibition and apoptosis of pancreatic cancer
      cells in vitro.
AB  - BACKGROUND: To explore the anti-tumor effects of parthenolide in human pancreatic
      cancer. METHODS: BxPC-3 cell, a human pancreatic cancer, was treated with
      parthenolide at different concentrations. The MTT assay was used to analyze cell
      viability. Flow cytometry and DNA fragmentation analysis were applied to evaluate
      apoptosis after parthenolide treatment. The wound closure and cell invasion assay
      were also employed in the study. Western blotting was used to demonstrate Bad,
      Bcl-2, Bax, caspase-9 and pro-caspase-3 expression. RESULTS: The MTT assay
      indicated that the pancreatic cancer growth could be dose-dependently inhibited
      by parthenoolide. This phenomenon was confirmed by flow cytometry and DNA
      fragmentation analysis. The wound closure assay and cell invasion assay showed
      that BxPC-3 cell was significantly suppressed by parthenolide at 7.5 microM and
      15 microM. Western Blotting demonstrated the Bcl-2 and pro-caspase-3 were down
      regulated while the Bax and caspase-9 were up-regulated. No alteration in Bad
      expression was found after treatment. CONCLUSIONS: The parthenolide can inhibit
      the cell growth, migration, and induce the apoptosis in human pancreatic cancer.
      These findings may provide a novel approach for pancreatic cancer treatment.

PMID- 20698987
TI  - Lamellipodium extension and membrane ruffling require different SNARE-mediated
      trafficking pathways.
AB  - BACKGROUND: Intracellular membrane traffic is an essential component of the
      membrane remodeling that supports lamellipodium extension during cell adhesion.
      The membrane trafficking pathways that contribute to cell adhesion have not been
      fully elucidated, but recent studies have implicated SNARE proteins. Here, the
      functions of several SNAREs (SNAP23, VAMP3, VAMP4 and syntaxin13) are
      characterized during the processes of cell spreading and membrane ruffling.
      RESULTS: We report the first description of a SNARE complex, containing SNAP23,
      syntaxin13 and cellubrevin/VAMP3, that is induced by cell adhesion to an
      extracellular matrix. Impairing the function of the SNAREs in the complex using
      inhibitory SNARE domains disrupted the recycling endosome, impeded delivery of
      integrins to the cell surface, and reduced haptotactic cell migration and
      spreading. Blocking SNAP23 also inhibited the formation of PMA-stimulated, F
      actin-rich membrane ruffles; however, membrane ruffle formation was not
      significantly altered by inhibition of VAMP3 or syntaxin13. In contrast, membrane
      ruffling, and not cell spreading, was sensitive to inhibition of two SNAREs
      within the biosynthetic secretory pathway, GS15 and VAMP4. Consistent with this,
      formation of a complex containing VAMP4 and SNAP23 was enhanced by treatment of
      cells with PMA. The results reveal a requirement for the function of a SNAP23
      syntaxin13-VAMP3 complex in the formation of lamellipodia during cell adhesion
      and of a VAMP4-SNAP23-containing complex during PMA-induced membrane ruffling.
      CONCLUSIONS: Our findings suggest that different SNARE-mediated trafficking
      pathways support membrane remodeling during ECM-induced lamellipodium extension
      and PMA-induced ruffle formation, pointing to important mechanistic differences
      between these processes.

PMID- 20698988
TI  - DBSolve Optimum: a software package for kinetic modeling which allows dynamic
      visualization of simulation results.
AB  - BACKGROUND: Systems biology research and applications require creation,
      validation, extensive usage of mathematical models and visualization of
      simulation results by end-users. Our goal is to develop novel method for
      visualization of simulation results and implement it in simulation software
      package equipped with the sophisticated mathematical and computational techniques
      for model development, verification and parameter fitting. RESULTS: We present
      mathematical simulation workbench DBSolve Optimum which is significantly improved
      and extended successor of well known simulation software DBSolve5. Concept of
      "dynamic visualization" of simulation results has been developed and implemented
      in DBSolve Optimum. In framework of the concept graphical objects representing
      metabolite concentrations and reactions change their volume and shape in
      accordance to simulation results. This technique is applied to visualize both
      kinetic response of the model and dependence of its steady state on parameter.
      The use of the dynamic visualization is illustrated with kinetic model of the
      Krebs cycle. CONCLUSION: DBSolve Optimum is a user friendly simulation software
      package that enables to simplify the construction, verification, analysis and
      visualization of kinetic models. Dynamic visualization tool implemented in the
      software allows user to animate simulation results and, thereby, present them in
      more comprehensible mode. DBSolve Optimum and built-in dynamic visualization
      module is free for both academic and commercial use. It can be downloaded
      directly from http://www.insysbio.ru.

PMID- 20698989
TI  - Clinic-epidemiological evaluation of ulcers in patients with leprosy sequelae and
      the effect of low level laser therapy on wound healing: a randomized clinical
      trial.
AB  - BACKGROUND: Mycobacterium leprae is the only pathogenic bacteria able to infect
      peripheral nerves. Neural impairment results in a set of sensitive, motor and
      autonomic disturbances, with ulcers originating primarily on the hands and feet.
      The study objectives were to analyze the clinic-epidemiological characteristics
      of patients attended at one specialized dressing service from a leprosy-endemic
      region of the Brazilian Amazon and to evaluate the effect of low level laser
      therapy (LLLT) on wound healing of these patients. METHODS: Clinic
      epidemiological evaluation of patients with leprosy sequelae was performed at the
      reference unit in sanitary dermatology of the state of Para in Brazil. We
      conducted anamnesis, identification of the regions affected by the lesions and
      measurement of ulcer depth and surface area. After that, we performed a
      randomized clinical trial. Fifty-one patients with ulcers related to leprosy were
      evaluated, twenty-five of them were randomly assigned to a low level laser
      therapy group or a control group. Patients were treated 3 times per week for 12
      weeks. Outcome measures were ulcer surface area, ulcer depth and the pressure
      ulcer scale for healing score (PUSH). RESULTS: Ninety-seven ulcers were
      identified, with a mean (SD) duration of 97.6 (111.7) months, surface area of 7.3
      (11.5) cm2, and depth of 6.0 (6.2) mm. Statistical analysis of the data
      determined that there were no significant differences in the variables analyzed
      before and after treatment with low level laser therapy. CONCLUSIONS: Ulcers in
      patients with leprosy remain a major source of economic and social losses, even
      many years after they have been cured of M. leprae infection. Our results
      indicate that it is necessary to develop new and more effective therapeutic
      tools, as low level laser therapy did not demonstrate any additional benefits to
      ulcer healing with the parameters used in this study. TRIAL REGISTRATION: The
      trial was registered at ClinicalTrials.gov as NCT00860717.

PMID- 20698990
TI  - Mental health of adolescents who abuse psychoactive substances in Enugu, Nigeria 
      a cross-sectional study.
AB  - BACKGROUND: Association between psychiatric morbidity and substance abuse among
      adolescent has been reported. However prevalence and pattern of such dysfunctions
      are unknown in our environment. AIMS: To determine the prevalence of psychosocial
      dysfunction and depressive symptoms among adolescents who abuse substance and
      also note the influence of socio-demographic factors and type of substance on the
      pattern of dysfunction. METHOD: A cross-sectional study was carried out among 900
      adolescents selected from 29 secondary schools in Enugu metropolis. A multi-stage
      sampling procedure was used to select the students. The student drug use
      questionnaire was used to screen respondents for substance abuse. Those who were
      abusing substance and matched controls (non substance abusers) were assessed for
      psychiatric symptoms using the 35-item Paediatric Symptom Checklist (PSC) and the
      Zung Self-rating Depression Scale (SDS). Social classification was done using the
      parental educational attainment and occupation. RESULT: A total of 290 students
      were current substance abusers. The substances most commonly abused were alcohol
      (31.6%), cola nitida (kola nut) (20.7%) and coffee (15.7%). Using the PSC scale,
      70 (24.1%) subjects compared to 29 (10.7%) of the controls had scores in the
      morbidity range of >or= 28 for psychosocial dysfunction. This was statistically
      significant (chi(2) = 17.57 p = 0.001). Fifty-four subjects (18.6%) had scores in
      the morbidity range of >or= 50 for depressive symptoms using the Zung SDS
      compared to 21 (7.7%) of controls. This was statistically significant (chi(2) =
      14.43, p = 0.001). Prevalence of dysfunction was not significantly related to age
      in both subjects and controls (chi(2) = 4.62, p = 0.010, chi(2) = 4.8, p = 0.10
      respectively). Also using both scales, there was no significant relationship
      between psychosocial dysfunction and gender or social class in both subjects and
      control. The prevalence of dysfunction using both scales was significantly higher
      in multiple abusers compared to single abusers. Subjects abusing alcohol scored
      more on both scales compared to those abusing other substances. CONCLUSION:
      Prevalence of psychosocial dysfunction is higher in adolescents abusing substance
      compare to controls. The prevalence of psychiatric morbidity was not related to
      the age, gender or social classes in the study population.We advocate periodic
      screening of our adolescents for drug abuse regular evaluation of such group for
      possible psychopathology.

PMID- 20698991
TI  - A treatment applying a biomechanical device to the feet of patients with knee
      osteoarthritis results in reduced pain and improved function: a prospective
      controlled study.
AB  - BACKGROUND: This study examined the effect of treatment with a novel
      biomechanical device on the level of pain and function in patients with knee OA.
      METHODS: Patients with bilateral knee OA were enrolled to active and control
      groups. Patients were evaluated at baseline, at 4 weeks and at the 8-week
      endpoint. A novel biomechanical device was individually calibrated to patients
      from the active group. Patients from the control group received an identical foot
      worn platform without the biomechanical elements. Primary outcomes were the WOMAC
      Index and ALF assessments. RESULTS: There were no baseline differences between
      the groups. At 8 weeks, the active group showed a mean improvement of 64.8% on
      the WOMAC pain scale, a mean improvement of 62.7% on the WOMAC function scale,
      and a mean improvement of 31.4% on the ALF scale. The control group demonstrated
      no improvement in the above parameters. Significant differences were found
      between the active and control groups in all the parameters of assessment.
      CONCLUSIONS: The biomechanical device and treatment methodology is effective in
      significantly reducing pain and improving function in knee OA patients.The study
      is registered at clinicaltrials.gov, identifier NCT00457132,
      http://www.clinicaltrials.gov/ct/show/NCT00457132?order=1.

PMID- 20698992
TI  - Duodenal obstruction - an unusual presentation of Strongyloides stercoralis
      enteritis: a case report.
AB  - BACKGROUND: Intestinal obstruction is a poorly recognized and probably
      underreported complication of strongyloidiasis. We present herein an unusual
      case, of complete duodenal obstruction caused by S. stercoralis. METHODS: A
      systematic review of the literature examining the clinical course, diagnostic
      methods, and outcome of this rare complication of strongyloidiasis was performed.
      RESULTS: A 42-year-old woman presented with a 5-month history of abdominal pain,
      vomit, and weight loss. An abdominal CT scan showed an obstruction of the third
      part of the duodenum. Segmental intestinal resection was carried out and
      histopathology examination revealed heavy Strongyloides stercoralis infestation.
      Duodenal obstruction is a rare complication of S. stercoralis infection, with
      only 8 cases described in the literature since 1970. Most of the patients are
      males, middle-aged, and the diagnosis was made by duodenal aspirate/biopsy, or
      analysis of surgical specimen. CONCLUSIONS: Duodenal obstruction is an unusual,
      but potential fatal, complication of S. stercoralis infection. The large spectrum
      of clinical manifestation and lack of classic clinical syndrome make the final
      diagnosis of strongyloidiasis extremely difficult. A high index of suspicion,
      mainly in patients from endemic areas, is needed for correct and early diagnosis
      of this uncommon presentation of Strogyloides stercoralis enteritis.

PMID- 20698993
TI  - A method for selecting cis-acting regulatory sequences that respond to small
      molecule effectors.
AB  - BACKGROUND: Several cis-acting regulatory sequences functioning at the level of
      mRNA or nascent peptide and specifically influencing transcription or translation
      have been described. These regulatory elements often respond to specific
      chemicals. RESULTS: We have developed a method that allows us to select cis
      acting regulatory sequences that respond to diverse chemicals. The method is
      based on the beta-lactamase gene containing a random sequence inserted into the
      beginning of the ORF. Several rounds of selection are used to isolate sequences
      that suppress beta-lactamase expression in response to the compound under study.
      We have isolated sequences that respond to erythromycin, troleandomycin,
      chloramphenicol, meta-toluate and homoserine lactone. By introducing synonymous
      and non-synonymous mutations we have shown that at least in the case of
      erythromycin the sequences act at the peptide level. We have also tested the
      cross-activities of the constructs and found that in most cases the sequences
      respond most strongly to the compound on which they were isolated. CONCLUSIONS:
      Several selected peptides showed ligand-specific changes in amino acid
      frequencies, but no consensus motif could be identified. This is consistent with
      previous observations on natural cis-acting peptides, showing that it is often
      impossible to demonstrate a consensus. Applying the currently developed method on
      a larger scale, by selecting and comparing an extended set of sequences, might
      allow the sequence rules underlying the activity of cis-acting regulatory
      peptides to be identified.

PMID- 20698994
TI  - Survivin gene silencing sensitizes prostate cancer cells to selenium growth
      inhibition.
AB  - BACKGROUND: Prostate cancer is a leading cause of cancer-related death in men
      worldwide. Survivin is a member of the inhibitor of apoptosis (IAP) protein
      family that is expressed in the majority of human tumors including prostate
      cancer, but is barely detectable in terminally differentiated normal cells.
      Downregulation of survivin could sensitize prostate cancer cells to
      chemotherapeutic agents in vitro and in vivo. Selenium is an essential trace
      element. Several studies have shown that selenium compounds inhibit the growth of
      prostate cancer cells. The objective of this study is to investigate whether
      survivin gene silencing in conjunction with selenium treatment could enhance the
      therapeutic efficacy for prostate cancer and to elucidate the underlying
      mechanisms. METHODS: Expression of survivin was analyzed in a collection of
      normal and malignant prostatic tissues by immunohistochemical staining. In vitro
      studies were conducted in PC-3M, C4-2B, and 22Rv1 prostate cancer cells. The
      effect of selenium on survivin expression was analyzed by Western blotting and
      semi-quantitative RT-PCR. Survivin gene knockdown was carried out by transfecting
      cells with a short hairpin RNA (shRNA) designed against survivin. Cell
      proliferation was quantitated by the 3-(4,5-Dimethylthiazol-2-yl)- 2,5
      Diphenyltetrazolium Bromide (MTT) assay and apoptosis by propidium iodide
      staining followed by flow cytometry analysis. Finally, in vivo tumor growth assay
      was performed by establishing PC-3M xenograft in nude mice and monitoring tumor
      growth following transfection and treatment. RESULTS: We found that survivin was
      undetectable in normal prostatic tissues but was highly expressed in prostate
      cancers. Survivin knockdown or selenium treatment inhibited the growth of
      prostate cancer cells, but the selenium effect was modest. In contrast to what
      have been observed in other cell lines, selenium treatment had little or no
      effect on survivin expression in several androgen-independent prostate cancer
      cell lines. Survivin knockdown sensitized these cells to selenium growth
      inhibition and apoptosis induction. In nude mice bearing PC-3M xenografts,
      survivin knockdown synergizes with selenium in inhibiting tumor growth.
      CONCLUSIONS: Selenium could inhibit the growth of hormone-refractory prostate
      cancer cells both in vitro and in vivo, but the effects were modest. The growth
      inhibition was not mediated by downregulating survivin expression. Survivin
      silencing greatly enhanced the growth inhibitory effects of selenium.

PMID- 20698995
TI  - Validation of the ERS standard citric acid cough challenge in healthy adult
      volunteers.
AB  - Protocols measuring cough sensitivity can vary in terms of nebuliser, tussive
      agent, single and dose response. A definitive method for measuring cough
      sensitivity needs to be established.The ERS guidelines recommend the KoKo
      DigiDoser (KD) delivery system. Study aim, was to compare the reproducibility of
      this citric acid (CA) cough challenge and previously established Mefar dosimeter
      (MD) protocol.39 (female 26) volunteers mean age (40.4 yrs) were randomised to
      either KD or MD. Intra-day and inter-day reproducibility was compared.We
      calculated the concentration of citric acid evoking 2 coughs (C2).The geometric
      mean C2 (95%CI) was similar for both KD and MD, of 263 (200,339) mM and 209
      (151,288) mM respectively.The mean KD C2 was not significantly different. (F =
      0.807, p = 0.93) from baseline over 1, 2, and 4 hrs however, the MD demonstrated
      significant variability (F = 7.85, P < 0.001)Measuring mean log C2 at baseline
      and at 2 weeks, the KD demonstrated a stronger intraclass correlation of log C2
      at baseline with 2 week log C2, ICC = 0.70 than was shown with the Mefar, ICC =
      0.41Administering CA from KD offers a reproducible cough challenge in healthy
      volunteers. The results correlate well with the MD challenge but offer greater
      intra-day and inter-day reproducibility. TRIAL REGISTRATION: Current controlled
      trials ISRCTN98385033.

PMID- 20698996
TI  - Identification of host proteins associated with HIV-1 preintegration complexes
      isolated from infected CD4+ cells.
AB  - An integrated HIV-1 genomic DNA leads to an infected cell becoming either an
      active or a latent virus-producing cell. Upon appropriate activation, a latently
      infected cell can result in production of progeny viruses that spread the
      infection to uninfected cells. The host proteins influence several steps of HIV-1
      infection including formation of the preintegration complex (PIC), a key
      nucleoprotein intermediate essential for integration of reverse transcribed viral
      DNA into the chromosome. Much effort has gone into the identification of host
      proteins contributing to the assembly of functional PICs. Experimental approaches
      included the use of yeast two-hybrid system, co-immunoprecipitation, affinity
      tagged HIV-1 viral proteins and in vitro reconstitution of salt-stripped PIC
      activity. Several host proteins identified using these approaches have been shown
      to affect HIV-1 replication in cells and influence catalytic activities of
      recombinant IN in vitro. However, the comprehensive identification and
      characterization of host proteins associated with HIV-1 PICs of infected cells
      have been hindered in part by the technical limitation in acquiring sufficient
      amount of catalytically active PICs. To efficiently identify additional host
      factors associated with PICs in infected cells, we have developed the following
      novel approach. The catalytically active PICs from HIV-1-infected CD4+ cells were
      isolated using biotinylated target DNA, and the proteins selectively co-purifying
      with PICs have been analyzed by mass spectrometry. This technology enabled us to
      reveal at least 19 host proteins that are associated with HIV-1 PICs, of which 18
      proteins have not been described previously with respect to HIV-1 integration.
      Physiological functions of the identified proteins range from chromatin
      organization to protein transport. A detailed characterization of these host
      proteins could provide new insights into the mechanism of HIV-1 integration and
      uncover new antiviral targets to block HIV-1 integration.

PMID- 20698997
TI  - Targeting lymphatic vessel functions through tyrosine kinases.
AB  - The lymphatic vascular system is actively involved in tissue fluid homeostasis,
      immune surveillance and fatty acid transport. Pathological conditions can arise
      from injury to the lymphatics, or they can be recruited in the context of cancer
      to facilitate metastasis. Protein tyrosine kinases are central players in signal
      transduction networks and regulation of cell behavior. In the lymphatic
      endothelium, tyrosine kinases are involved in processes such as the maintenance
      of existing lymphatic vessels, growth and maturation of new vessels and
      modulation of their identity and function. As such, they are attractive targets
      for both existing inhibitors and the development of new inhibitors which affect
      lymphangiogenesis in pathological states such as cancer. RNAi screening provides
      an opportunity to identify the functional role of tyrosine kinases in the
      lymphatics. This review will discuss the role of tyrosine kinases in lymphatic
      biology and the potential use of inhibitors for anti-lymphangiogenic therapy.

PMID- 20698998
TI  - Determinants of seropositivity among HPV-16/18 DNA positive young women.
AB  - BACKGROUND: Not all women infected with HPV-16/18 have detectable levels of HPV
      16/18 antibodies, those who seroconvert develop low antibody levels, and
      seroconversion occurs typically several months post-infection. We evaluated
      determinants of seropositivity among 646 women infected with HPV-16 and/or HPV
      18. METHODS: Data are from the enrollment visit of the NCI-sponsored Costa Rica
      HPV Vaccine Trial. Sera were tested for HPV-16/18 antibodies by ELISA; cervical
      specimens were tested for HPV DNA using HC2 and SPF10/LiPA25. Odds ratios (OR)
      and 95% confidence intervals (CI) were computed. RESULTS: Among HPV-16/18 DNA
      positives, seropositivity was 63.0% and 57.5%, respectively. Among HPV-16 DNA
      positives, seropositivity increased with lifetime number of sexual partners (p
      trend = 0.01). Women with abnormal cytology and/or high viral load had a 1.63
      2.79-fold increase in the detection of antibodies compared to women with normal
      cytology/low viral load. Current users of oral contraceptives had a 1.88-fold
      (95%CI, 1.14-3.09) increased detection of antibodies and current users of
      injectables had a 3.38-fold (95%CI, 1.39-8.23) increased detection compared to
      never users. Among HPV-18 DNA positive women, seropositivity was associated with
      current oral contraceptive use (OR 2.47; 95%CI 1.08-5.65). CONCLUSIONS: Factors
      associated with sustained HPV exposure (abnormal cytology, elevated HPV viral
      load, increasing lifetime partners) were predictive of HPV-16 seropositivity.
      Hormonal contraceptive use was associated with seropositivity suggesting an
      effect of hormones on immune responses to HPV. Patterns were less consistent for
      HPV-18. Follow up of incident HPV infections to evaluate seroconversion and their
      determinants is needed.

PMID- 20698999
TI  - Fluoroscopically guided transforaminal epidural dry needling for lumbar spinal
      stenosis using a specially designed needle.
AB  - BACKGROUND: This report describes the methodological approach and clinical
      application of a minimally invasive intervention to treat lumbar spinal stenosis
      (LSS). METHODS: Thirty-four patients with LSS underwent fluoroscopically guided
      transforaminal epidural dry needling using a specially designed flexed Round
      Needle. The needle was inserted 8-12 cm lateral to the midline at the level of
      the stenosis and advanced to a position between the anterior side of the facet
      joint and pedicle up to the outer-third of the pedicle. The needle was advanced
      medially and backed laterally within a few millimetres along the canal side of
      the inferior articular process between the facet joint and pedicle. The procedure
      was completed when a marked reduction in resistance was felt at the tip of the
      needle. The procedure was performed bilaterally at the level of the stenosis.
      RESULTS: The average follow-up period was 12.9 +/- 1.1 months. The visual
      analogue scale (VAS) pain score was reduced from 7.3 +/- 2.0 to 4.6 +/- 2.5
      points, the Oswestry Disability Index (ODI) score decreased from 41.4 +/- 17.2 to
      25.5 +/- 12.6% and the average self-rated improvement was 52.6 +/- 33.1%. The VAS
      scores indicated that 14 (41.2%) patients reported a "good" to "excellent"
      treatment response, while 11 (32.4%) had a "good" to "excellent" treatment
      response on the ODI and 22 (64.7%) had a "good" to "excellent" treatment response
      on the self-rated improvement scale. CONCLUSIONS: These results suggest that
      fluoroscopically guided transforaminal epidural dry needling is effective for
      managing LSS.

PMID- 20699000
TI  - Involvement of tumor necrosis factor-alpha in the upregulation of CXCR4
      expression in gastric cancer induced by Helicobacter pylori.
AB  - BACKGROUND: H. pylori, whose infection increases tumor invasiveness and
      metastasis, is generally labelled as the strongest risk factor for the
      development of gastric cancer. It appears not to be a coincidence that there is
      also an overexpression of CXCR4 and an obvious involvement in gastric cancer
      metastasis. The aim of this study attempts to investigate and further to
      establish a link between them. With H. pylori being a potent inducer of TNF
      alpha, whether TNF-alpha, a tumor promoter, is involved in the induction of CXCR4
      expression by H. pylori was also under research in this study. METHODS:
      Expression of CXCR4, TNF-alpha, IL-6 and IL-1 beta mRNA was determined by real
      time PCR. CXCR4 protein expression was detected by Western blotting.
      Concentrations of TNF-alpha, IL-6 and IL-1 beta in cell culture supernatants were
      measured using the Quantikine Elisa kit. To abrogate TNF-alpha expression in
      HGC27 cells, TNF-alpha RNAi plasmid was used to transfect them. RESULTS: Levels
      of CXCR4 and TNF-alpha mRNA were significantly higher in H. pylori-positive
      gastric cancers (n = 19) compared to H. pylori-negative ones (n = 15). A
      subsequently Spearman's rank correlation test showed there was a positive
      correlation between the level of CXCR4 mRNA and that of TNF-alpha in 34 primary
      gastric cancers. Other results followed: Expression of CXCR4 and TNF-alpha was
      upregulated in gastric cancer cell MKN45 and HGC27 after infection with H. pylori
      26695 (cag PAI+ ) or Tx30a (cag PAI- ); The induction of CXCR4 expression by H.
      pylori was inhibited significantly by a neutralizing TNF-alpha antibody,
      infliximab; CXCR4 expression was upregulated in MKN45 cells after treatment with
      exogenous TNF-alpha or co-culture with macrophage, and was downregulated in HGC27
      cells after transfection with TNF-alpha RNAi plasmid. There was a significant
      increase in the migration of MKN45 cells treated with H. pylori 26695, and a
      strong inhibition when AMD 3100, a CXCR4 antagonist, or infliximab, was added.
      CONCLUSIONS: Our findings demonstrated that H. pylori upregulates CXCR4
      expression in gastric cancer through TNF-alpha.

PMID- 20699001
TI  - Identification of a novel iron regulated basic helix-loop-helix protein involved
      in Fe homeostasis in Oryza sativa.
AB  - BACKGROUND: Iron (Fe) is the most limiting micronutrient element for crop
      production in alkaline soils. A number of transcription factors involved in
      regulating Fe uptake from soil and transport in plants have been identified.
      Analysis of transcriptome data from Oryza sativa grown under limiting Fe
      conditions reveals that transcript abundances of several genes encoding
      transcription factors are altered by Fe availability. These transcription factors
      are putative regulators of Fe deficiency responses. RESULTS: Transcript abundance
      of one nuclear located basic helix-loop-helix family transcription factor,
      OsIRO3, is up-regulated from 25- to 90-fold under Fe deficiency in both root and
      shoot respectively. The expression of OsIRO3 is specifically induced by Fe
      deficiency, and not by other micronutrient deficiencies. Transgenic rice plants
      over-expressing OsIRO3 were hypersensitive to Fe deficiency, indicating that the
      Fe deficiency response was compromised. Furthermore, the Fe concentration in
      shoots of transgenic rice plants over-expressing OsIRO3 was less than that in
      wild-type plants. Analysis of the transcript abundances of genes normally induced
      by Fe deficiency in OsIRO3 over-expressing plants indicated their induction was
      markedly suppressed. CONCLUSION: A novel Fe regulated bHLH transcription factor
      (OsIRO3) that plays an important role for Fe homeostasis in rice was identified.
      The inhibitory effect of OsIRO3 over-expression on Fe deficiency response gene
      expression combined with hypersensitivity of OsIRO3 over-expression lines to low
      Fe suggest that OsIRO3 is a negative regulator of the Fe deficiency response in
      rice.

PMID- 20699002
TI  - The increase of plasma galectin-9 in a patient with insulin allergy: a case
      report.
AB  - Allergic reaction to insulin is known to be associated with eosinophilia and
      hyper IgE. Recent report showed that eosinophilia is related with the increased
      synthesis of galectin-9 (GAL-9) and osteopontin (OPN). Here, we examined plasma
      levels of GAL-9 and OPN first time in a case of 65-year old patient with insulin
      allergy. Insulin aspart & insulin aspart 30 mix were given to the patient and an
      elevation of the eosinophil count (8440/mul, 17.6 fold) and a moderate increase
      of IgE (501 U/ml, reference range: 10-350 U/ml), eotaxin-3 (168 pg/ml, 2 fold),
      histamine (0.95 ng/ml, 5.3 fold) were found 33 days later. The plasma levels of
      GAL-9 and OPN were 22.5 and 1.7 fold higher than the cut-off point, respectively.
      After one month cessation of insulin therapy, elevations of the eosinophil count
      (3,480/mul; 7.3 fold), and OPN (1.4 fold) still occurred but the GAL-9 levels
      became normal. Therefore, we noted the increases of GAL-9 and OPN in plasma for
      the first time in a patient with insulin allergy and propose that GAL-9 reflects
      the conditions of allergy more accurately.

PMID- 20699003
TI  - Comparative transcriptional profiling analysis of the two daughter cells from
      tobacco zygote reveals the transcriptome differences in the apical and basal
      cells.
AB  - BACKGROUND: In angiosperm, after the first asymmetric zygotic cell division, the
      apical and basal daughter cells follow distinct development pathways. Global
      transcriptome analysis of these two cells is essential in understanding their
      developmental differences. However, because of the difficulty to isolate the in
      vivo apical and basal cells of two-celled proembryo from ovule and ovary in
      higher plants, the transcriptome analysis of them hasn't been reported. RESULTS:
      In this study, we developed a procedure for isolating the in vivo apical and
      basal cells of the two-celled proembryo from tobacco (Nicotiana tabacum), and
      then performed a comparative transcriptome analysis of the two cells by
      suppression subtractive hybridization (SSH) combined with macroarray screening.
      After sequencing, we identified 797 differentially expressed ESTs corresponding
      to 299 unigenes. Library sequence analysis successfully identified tobacco
      homologies of genes involved in embryogenesis and seed development. By
      quantitative real-time PCR, we validated the differential expression of 40 genes,
      with 6 transcripts of them specifically expressed in the apical or basal cell.
      Expression analysis also revealed some transcripts displayed cell specific
      activation in one of the daughter cells after zygote division. These differential
      expressions were further validated by in situ hybridization (ISH). Tissue
      expression pattern analysis also revealed some potential roles of these candidate
      genes in development. CONCLUSIONS: The results show that some differential or
      specific transcripts in the apical and basal cells of two-celled proembryo were
      successfully isolated, and the identification of these transcripts reveals that
      these two daughter cells possess distinct transcriptional profiles after zygote
      division. Further functional work on these differentially or specifically
      expressed genes will promote the elucidation of molecular mechanism controlling
      early embryogenesis.

PMID- 20699004
TI  - Adverse events in total knee arthroplasty: Results of a physician independent
      survey in 260 patients.
AB  - PURPOSE: Identification of all common and potentially avoidable adverse events is
      crucial to further improve the quality of medical care. The intention of the
      current study was to evaluate a standardized physician independent survey format
      on adverse events in total knee arthroplasty. The protocol for reporting adverse
      drug events following the International Conference of Harmonisation of technical
      requirements for registration of pharmaceuticals for human use (ICH) was adopted
      for adverse events occurring during surgical interventions. MATERIAL AND METHODS:
      Data of a prospective sequential cohort trial introducing a clinical pathway for
      total knee arthroplasty was analysed. Reporting of adverse events was done by a
      physician independent study nurse using the modified ICH-Good Clinical Practice
      (GCP) format (Structure and Content of Clinical study reports - E3) in 260
      patients. The adverse events were graded to their severity and their potential
      relation to surgical treatment. RESULTS: A total of 55 patients (21%) suffered
      from an adverse event and 16 (6%) from a serious adverse event. In 38 patients'
      one adverse event occurred, 12 patients showed 2 adverse events and 5 patients
      suffered from a combination of an adverse and a serious adverse event. A serious
      adverse event alone occurred in 11 patients. The incidence of adverse events
      (Fisher p = 0.448) and serious adverse (p = 0.126) events showed no significant
      difference between the two cohorts. The most common adverse events were deep vein
      thrombosis (8% and 5%) followed by wound healing problems (1% and 0%) and
      haematoma (1% and 3%). A wide range of non surgical adverse events were recorded
      with low incidence levels. CONCLUSION: The use of the modified ICH-GCP format
      supports standardization of adverse event reporting. Routine assessment of
      adverse events by a study nurse revealed higher incidence rates of adverse events
      in total knee arthroplasty. We recommend the implementation of trained
      paramedical staff for the documentation of adverse events in routine clinical
      care.

PMID- 20699005
TI  - Dynamics of Sundarban estuarine ecosystem: eutrophication induced threat to
      mangroves.
AB  - BACKGROUND: Sundarbans is the largest chunk of mangrove forest and only tiger
      mangrove land in the world. Compared to the rich species diversity and
      uniqueness, very few studies have so far been conducted here, mainly due to its
      inaccessibility. This study explores water quality, density of biomass, species
      diversity, phytoplankton abundance and bacterial population of a tidal creek in
      Sunderban estuary during the post and pre monsoon period of 2008-09. RESULTS:
      Phytoplankton community was observed to be dominated by diatoms
      (Biacillariophyceae) followed by Pyrrophyceae (Dinoflagellates) and
      Chlorophyceae. A total of 46 taxa belonging to 6 groups were recorded. Other
      algal groups were Cyanophyceae, Euglenophyceae and Chrysophyceae. Species
      diversity was highest in summer (March) and lowest in winter season (November) in
      all the sample stations indicating its close correlation with ambient
      temperature. Species evenness was fairly high in all five stations throughout the
      study period. Present study indicated that dissolved oxygen, nutrients and
      turbidity are the limiting factors for the phytoplankton biomass. The estuary was
      in eutrophic condition (Chlorophyll-a >/=10 mug/L) in winter. During the month of
      May phytoplankton biomass declined and at high salinity level (21.2PSU) new
      phytoplankton species take over, which are definitely better resilient to the
      high saline environment. Bio-indicator species like Polykrikos schwartzil,
      Dinophysis norvegica and Prorocentrum concavum points to moderately polluted
      water quality of the estuary. CONCLUSION: Eutrophication as well as presence of
      toxic Dinoflagellates and Cyanophyceae in the tidal creek of Sundarban estuary
      definitely revealed the deteriorated status of the water quality. The structure
      and function of the mangrove food web is unique, driven by both marine and
      terrestrial components. But little attention has been paid so far to the adaptive
      responses of mangrove biota to the various disturbances, and now our work unfolds
      the fact that marine status of Sundarban estuary is highly threatened which in
      turn will affect the ecology of the mangrove. This study indicates that ecosystem
      dynamics of the world heritage site Sundarban may facilitate bioinvasion putting
      a question mark on the sustainability of mangroves.

PMID- 20699006
TI  - Molecular characterization of vernalization loci VRN1 in wild and cultivated
      wheats.
AB  - BACKGROUND: Variability of the VRN1 promoter region of the unique collection of
      spring polyploid and wild diploid wheat species together with diploid goatgrasses
      (donor of B and D genomes of polyploid wheats) were investigated. Accessions of
      wild diploid (T. boeoticum, T. urartu) and tetraploid (T. araraticum, T.
      timopheevii) species were studied for the first time. RESULTS: Sequence analysis
      indicated great variability in the region from -62 to -221 nucleotide positions
      of the VRN1 promoter region. Different indels were found within this region in
      spring wheats. It was shown that VRN1 promoter region of B and G genome can also
      contain damages such as the insertion of the transposable element.Some
      transcription factor recognition sites including hybrid C/G-box for TaFDL2
      protein known as the VRN1 gene upregulator were predicted inside the variable
      region. It was shown that deletions leading to promoter damage occurred in
      diploid and polyploid species independently. DNA transposon insertions first
      occurred in polyploid species. At the same time, the duplication of the promoter
      region was observed in A genomes of polyploid species. CONCLUSIONS: We can
      conclude that supposed molecular mechanism of the VRN1 gene activating in
      cultivated diploid wheat species T. monococcum is common also for wild T.
      boeoticum and was inherited by T. monococcum. The spring polyploids are not
      related in their origin to spring diploids. The spring T. urartu and goatgrass
      accessions have another mechanism of flowering activation that is not connected
      with indels in VRN1 promoter region. All obtained data may be useful for detailed
      insight into origin of spring wheat forms in evolution and domestication process.

PMID- 20699007
TI  - A novel tissue-specific meta-analysis approach for gene expression predictions,
      initiated with a mammalian gene expression testis database.
AB  - BACKGROUND: In the recent years, there has been a rise in gene expression
      profiling reports. Unfortunately, it has not been possible to make maximum use of
      available gene expression data. Many databases and programs can be used to derive
      the possible expression patterns of mammalian genes, based on existing data.
      However, these available resources have limitations. For example, it is not
      possible to obtain a list of genes that are expressed in certain conditions. To
      overcome such limitations, we have taken up a new strategy to predict gene
      expression patterns using available information, for one tissue at a time.
      RESULTS: The first step of this approach involved manual collection of maximum
      data derived from large-scale (genome-wide) gene expression studies, pertaining
      to mammalian testis. These data have been compiled into a Mammalian Gene
      Expression Testis-database (MGEx-Tdb). This process resulted in a richer
      collection of gene expression data compared to other databases/resources, for
      multiple testicular conditions. The gene-lists collected this way in turn were
      exploited to derive a 'consensus' expression status for each gene, across
      studies. The expression information obtained from the newly developed database
      mostly agreed with results from multiple small-scale studies on selected genes. A
      comparative analysis showed that MGEx-Tdb can retrieve the gene expression
      information more efficiently than other commonly used databases. It has the
      ability to provide a clear expression status (transcribed or dormant) for most
      genes, in the testis tissue, under several specific physiological/experimental
      conditions and/or cell-types. CONCLUSIONS: Manual compilation of gene expression
      data, which can be a painstaking process, followed by a consensus expression
      status determination for specific locations and conditions, can be a reliable way
      of making use of the existing data to predict gene expression patterns. MGEx-Tdb
      provides expression information for 14 different combinations of specific
      locations and conditions in humans (25,158 genes), 79 in mice (22,919 genes) and
      23 in rats (14,108 genes). It is also the first system that can predict
      expression of genes with a 'reliability-score', which is calculated based on the
      extent of agreements and contradictions across gene-sets/studies. This new
      platform is publicly available at the following web address:
      http://resource.ibab.ac.in/MGEx-Tdb/.

PMID- 20699008
TI  - Relationship between rickets and incomplete distal renal tubular acidosis in
      children.
AB  - BACKGROUND: In the Sub Saharan Africa Rickets has now been established to be due
      primarily to calcium deficiency and sometimes in combination with vitamin D
      deficiency. The main thrust of management is calcium supplementation with or
      without vitamin D. An observation was made that some children with nutritional
      rickets do not respond to this management modality. The recently reported high
      prevalence of Incomplete Distal Renal Tubular Acidosis (idRTA) in adults with
      osteoporosis as brought to fore the possibility of this being a possible cause of
      calcium wastage and therefore the poor response in these group of children with
      rickets. AIM: To determine the prevalence of idRTA amongst a cohort of subjects
      with ricketsTo show a relationship between rickets and incomplete distal renal
      acidosisTo determine the response of children with rickets and idRTA to addition
      of Shohl's solution to therapy METHODOLOGY: Two separate cohorts of children with
      rickets performed the ammonium chloride loading test to detect those with
      incomplete renal tubular acidosis. Following identification for idRTA, Shohl's
      solution was added to therapy of calcium and vitamin D supplementation and their
      response compared to those without idRTA on calcium and vitamin D supplementation
      solely. RESULTS: 50 children with rickets aged from two to six years of age and
      composed of 29 females and 21males were investigated. Incomplete renal tubular
      acidosis was found in 38% of them. Prevalence of idRTA was highest amongst those
      aged 3-6 years of age. Those with idRTA had worse limb deformities, biochemical
      and radiological parameters than those who hadn't. Rate of response on those with
      idRTA treated with Shohl's solution was at par with those without idRTA.
      CONCLUSION: Incomplete idRTA exist amongst children with rickets and should be
      looked out for in severe rickets and older children. Treatment of idRTA will lead
      to optimal response and healing of rickets.

PMID- 20699009
TI  - YAO is a nucleolar WD40-repeat protein critical for embryogenesis and
      gametogenesis in Arabidopsis.
AB  - BACKGROUND: In flowering plants, gametogenesis generates multicellular male and
      female gametophytes. In the model system Arabidopsis, the male gametophyte or
      pollen grain contains two sperm cells and a vegetative cell. The female
      gametophyte or embryo sac contains seven cells, namely one egg, two synergids,
      one central cell and three antipodal cells. Double fertilization of the central
      cell and egg produces respectively a triploid endosperm and a diploid zygote that
      develops further into an embryo. The genetic control of the early embryo
      patterning, especially the initiation of the first zygotic division and the
      positioning of the cell plate, is largely unknown. RESULTS: Here we report the
      characterization of a mutation, yaozhe (yao), that causes zygote arrest and
      misplacement of cell plate of the zygote, leading to early embryo lethality. In
      addition, gametophyte development is partially impaired. A small portion of the
      mutant embryo sacs are arrested at four-nucleate stage with aberrant nuclear
      positioning. Furthermore, the competence of male gametophytes is also
      compromised. YAO encodes a nucleolar protein with seven WD-repeats. Its
      homologues in human and yeast have been shown to be components of the U3 snoRNP
      complex and function in 18S rRNA processing. YAO is expressed ubiquitously, with
      high level of expression in tissues under active cell divisions, including embryo
      sacs, pollen, embryos, endosperms and root tips. CONCLUSIONS: Phenotypic analysis
      indicated that YAO is required for the correct positioning of the first zygotic
      division plane and plays a critical role in gametogenesis in Arabidopsis. Since
      YAO is a nucleolar protein and its counterparts in yeast and human are components
      of the U3 snoRNP complex, we therefore postulate that YAO is most likely involved
      in rRNA processing in plants as well.

PMID- 20699010
TI  - Cryptococcosis mimicking cutaneous cellulitis in a patient suffering from
      rheumatoid arthritis: a case report.
AB  - BACKGROUND: Cryptococcus neoformans is an encapsulated yeast and the most
      frequent cryptococcal species found in humans. Cryptococcosis is considered an
      opportunistic infection as it affects mainly immunosuppressed individuals. In
      humans, C. neoformans causes three types of infections: pulmonary cryptococcosis,
      cryptococcal meningitis and wound or cutaneous cryptococcosis. CASE PRESENTATION:
      An 81-year-old woman developed severe necrotizing cellulitis on her left arm
      without any preceding injury. The patient had been treated with systemic
      corticosteroids over twenty years for rheumatoid arthritis (RA). Skin biopsies of
      the wound area were initially interpreted as cutaneous vasculitis of unknown
      etiology. However, periodic acid Schiff staining and smear analysis later
      revealed structures consistent with Cryptococcus neoformans, and the infection
      was subsequently confirmed by culture. After the initiation of therapy with
      fluconazole 400 mg per day the general condition and the skin ulcers improved
      rapidly and the patient was discharged to a rehabilitation facility. Subsequently
      surgical debridement and skin grafting were performed. CONCLUSIONS: Opportunistic
      infections such as cryptococcosis can clinically and histologically mimic
      cutaneous vasculitis and have to be investigated rigorously as a differential
      diagnosis in immunosuppressed patients.

PMID- 20699011
TI  - The characterisation of AOP2: a gene associated with the biosynthesis of
      aliphatic alkenyl glucosinolates in Arabidopsis thaliana.
AB  - BACKGROUND: Glucosinolates, a group of nitrogen and sulfur containing compounds
      associated with plant-insect interactions, are produced by a number of important
      Brassicaceae crop species. In Arabidopsis the AOP2 gene plays a role in the
      secondary modification of aliphatic (methionine-derived) glucosinolates, namely
      the conversion of methylsulfinylalkyl glucosinolates to form alkenyl
      glucosinolates, and also influences aliphatic glucosinolate accumulation.
      RESULTS: This study characterises the primary structural variation in the coding
      sequences of the AOP2 gene and identifies three different AOP2 alleles based on
      polymorphisms in exon two. To help determine the regulatory mechanisms mediating
      AOP2 expression amongst accessions, AOP2 5' regulatory regions were also examined
      however no major differences were identified. Expression of the AOP2 gene was
      found to be most abundant in leaf and stem tissue and was also found to be light
      dependent, with a number of light regulatory elements identified in the promoter
      region of the gene. In addition, a study was undertaken to demonstrate that the
      Arabidopsis AOP2 gene product is functional in planta. The over-expression of a
      functional AOP2 allele was found to successfully convert the precursor
      methylsulfinyl alkyl glucosinolate into the alkenyl form. CONCLUSIONS: The
      expression of the AOP2 gene has been found to be influenced by light and is most
      highly expressed in the photosynthetic parts of the Arabidopsis plant. The level
      of AOP2 transcript decreases rapidly in the absence of light. AOP2 exists as at
      least three alleles in different Arabidopsis accessions and we have demonstrated
      that one of these, AOP2-2, is functionally able to convert methylsulfinyl
      glucosinolates into the alkenyl form. The demonstration of the in planta
      functionality of the Arabisopsis AOP2 gene is an important step in determining
      the feasibility of engineering glucosinolate profiles in food plants.

PMID- 20699012
TI  - A note on mate allocation for dominance handling in genomic selection.
AB  - Estimation of non-additive genetic effects in animal breeding is important
      because it increases the accuracy of breeding value prediction and the value of
      mate allocation procedures. With the advent of genomic selection these ideas
      should be revisited. The objective of this study was to quantify the efficiency
      of including dominance effects and practising mating allocation under a whole
      genome evaluation scenario. Four strategies of selection, carried out during five
      generations, were compared by simulation techniques. In the first scenario (MS),
      individuals were selected based on their own phenotypic information. In the
      second (GSA), they were selected based on the prediction generated by the Bayes A
      method of whole-genome evaluation under an additive model. In the third (GSD),
      the model was expanded to include dominance effects. These three scenarios used
      random mating to construct future generations, whereas in the fourth one (GSD +
      MA), matings were optimized by simulated annealing. The advantage of GSD over GSA
      ranges from 9 to 14% of the expected response and, in addition, using mate
      allocation (GSD + MA) provides an additional response ranging from 6% to 22%.
      However, mate selection can improve the expected genetic response over random
      mating only in the first generation of selection. Furthermore, the efficiency of
      genomic selection is eroded after a few generations of selection, thus, a
      continued collection of phenotypic data and re-evaluation will be required.

PMID- 20699014
TI  - Advances in mesenchymal stem cell-mediated gene therapy for cancer.
AB  - Mesenchymal stem cells have a natural tropism for tumours and their metastases,
      and are also considered immunoprivileged. This remarkable combination of
      properties has formed the basis for many studies investigating their potential as
      tumour-specific delivery vehicles for suicide genes, oncolytic viruses and
      secreted therapeutic proteins. The aim of the present review is to discuss the
      range of approaches that have been used to exploit the tumour-homing capacity of
      mesenchymal stem cells for gene delivery, and to highlight advances required to
      realize the full potential of this promising approach.

PMID- 20699013
TI  - Systems biology discoveries using non-human primate pluripotent stem and germ
      cells: novel gene and genomic imprinting interactions as well as unique
      expression patterns.
AB  - The study of pluripotent stem cells has generated much interest in both biology
      and medicine. Understanding the fundamentals of biological decisions, including
      what permits a cell to maintain pluripotency, that is, its ability to self-renew
      and thereby remain immortal, or to differentiate into multiple types of cells, is
      of profound importance. For clinical applications, pluripotent cells, including
      both embryonic stem cells and adult stem cells, have been proposed for cell
      replacement therapy for a number of human diseases and disorders, including
      Alzheimer's, Parkinson's, spinal cord injury and diabetes. One challenge in their
      usage for such therapies is understanding the mechanisms that allow the
      maintenance of pluripotency and controlling the specific differentiation into
      required functional target cells. Because of regulatory restrictions and
      biological feasibilities, there are many crucial investigations that are just
      impossible to perform using pluripotent stem cells (PSCs) from humans (for
      example, direct comparisons among panels of inbred embryonic stem cells from
      prime embryos obtained from pedigreed and fertile donors; genomic analysis of
      parent versus progeny PSCs and their identical differentiated tissues;
      intraspecific chimera analyses for pluripotency testing; and so on). However,
      PSCs from nonhuman primates are being investigated to bridge these knowledge gaps
      between discoveries in mice and vital information necessary for appropriate
      clinical evaluations. In this review, we consider the mRNAs and novel genes with
      unique expression and imprinting patterns that were discovered using systems
      biology approaches with primate pluripotent stem and germ cells.

PMID- 20699015
TI  - Experimental approaches for the generation of induced pluripotent stem cells.
AB  - Derivation of autologous induced pluripotent stem cells (iPSCs) through direct
      reprogramming of easily accessible somatic cells holds the potential to transform
      the field of regenerative medicine. Since Takahashi and Yamanaka's groundbreaking
      study describing the generation of iPSCs by retroviral-mediated delivery of
      defined transcription factors, substantial progress has been made to improve both
      the efficiency and safety of the method. These advances have provided new
      insights into the molecular mechanisms of reprogramming and promise to accelerate
      the clinical translation of iPSC technology. Here, we summarize current
      reprogramming methodologies with a focus on the production of transgene-free or
      genetically unmanipulated iPSCs and highlight important technical details that
      ultimately may influence the biological properties of pluripotent stem cells.

PMID- 20699016
TI  - [Acute abdominal symptoms in patients with a gastric band].
AB  - Three women aged 32, 35 and 37 years, respectively, presented with upper
      abdominal symptoms such as pain, nausea and vomiting. Their history revealed that
      an adjustable silicone gastric band had been implanted for the treatment of
      obesity one, four and seven years previously. Their symptoms were not immediately
      recognised as being possible complications of the gastric band and this caused
      treatment delay. In the first two patients ischaemic lesions were found at
      laparotomy. Their surgical treatment was successful. The third patient, however,
      was referred to the surgeon who had placed the gastric band, but she died in the
      mean time. Lack of recognition of symptoms caused by gastric banding and delay in
      diagnostic and therapeutic intervention may lead to very serious complications,
      or even death. Good diagnostic imaging and prompt therapeutic intervention can
      prevent the progression from herniation of the stomach through the silicone
      gastric band to irreversible ischaemia and eventually necrosis and perforation.

PMID- 20699018
TI  - [Haemorrhages due to vitamin C deficiency. Scurvy in the 21st century].
AB  - A 68-year-old female with an extensive history of unexplained problems presented
      at the Department of Internal Medicine for an analysis of painful cutaneous
      abnormalities of the lower legs. A systemic cause could not be found. Later on
      the general practitioner noted haematoma and petechiae and subsequently a
      hypovitaminosis C. The patient received active vitamin C supplement for this. The
      cutaneous abnormalities on the legs had significantly improved after 3 weeks.
      This patient was found to have symptomatic hypovitaminosis C, also known as
      scurvy, as a complication of an psychiatric disorder. Although scurvy might
      appear to be a disease of the past that rarely occurs nowadays, it should
      nevertheless be given due consideration. This requires a good history taking.

PMID- 20699017
TI  - [Mucocutaneous abnormalities in Chlamydia trachomatis-induced reactive
      arthritis].
AB  - Reactive arthritis (previously known as Reiters syndrome) is an inflammatory
      arthritis that is a type of spondyloarthropathy. The disease consists of the
      classical triad of arthritis, urethritis and conjunctivitis, but mucocutaneous
      abnormalities also frequently appear: balanitis circinata, keratoderma
      blennorrhagicum, aphthous ulcers in the mouth and nail disorders. These skin
      lesions are mainly found in reactive arthritis induced by Chlamydia trachomatis
      (Ct). Reactive arthritis is often triggered by a sexually transmitted infection
      (Chlamydia trachomatis) or an enteric infection (such as Salmonella or Shigella).
      It is thought that human antibodies against the pathogen cross-react with the HLA
      antigen (mainly HLA-B27). To distinguish between reactive arthritis and psoriatic
      arthritis, screening of the urine or synovium for Ct infection should be carried
      out. Acute reactive arthritis is treated with NSAIDs as the first choice. In
      addition, patients may receive an intra-articular injection of glucocorticoids.
      The mucocutaneous abnormalities respond well to topical glucocorticoids. Although
      in the Netherlands a Ct induced reactive arthritis is not yet treated with
      antibiotics, a recent published clinical trial in patients with a chronic Ct
      induced reactive arthritis showed a significant reduction in complaints in the
      group treated with a combination of antibiotics for 6 months, compared to the
      placebo group. Active genitourinary Ct infection should be treated with
      antibiotics, the first choice being azithromycin 1000 mg as a single dose. It is
      important that the patient's partner is tested at the same time and if necessary
      treated simultaneously to prevent reinfection.

PMID- 20699019
TI  - [The ship's log of Ellerbeek: common sense and serendipity in the treatment of
      scurvy].
AB  - In accordance with the usual practice, chief surgeon Joan Ellerbeek recorded his
      observations during his voyage with the East Indiaman Mars to the Cape of Good
      Hope in 1776 in a logbook for the Dutch East India Company. During the voyage he
      was confronted with an increasing number of scurvy patients. Intuitive insight
      and serendipity led him to try using the seaweed ('Gramen Marinum') which had
      grown on the ship as an anti-scurvy agent, in the empirical and medical tradition
      of his time. The results were spectacular. Not only James Lind should therefore
      be credited with the solution of the problem of scurvy. Many before and after
      him, including Ellerbeek, also made a contribution.

PMID- 20699020
TI  - [Reasons not to have your daughter vaccinated against the human papilloma virus
      in Twente: a questionnaire study].
AB  - OBJECTIVE: To gain insight into parents' decision-making process, and their
      reasons for participation in the human papilloma virus (HPV) vaccination
      programme in the Twente region, the Netherlands. DESIGN: Cross-sectional study by
      means of a questionnaire. METHODS: After the first vaccination round, a
      questionnaire was sent to the parents of 800 13-year-old girls, born in the year
      1996 and living in the Twente region. Data were collected on the socio
      demographic characteristics of the parents, their daughters' participation in the
      HPV vaccination programme (in which 13-15-year-olds were offered the vaccine
      previously offered only to 12-year-olds), and four determinants derived from the
      Health Belief Model (HBM): perceived susceptibility, severity, benefits and
      barriers. RESULTS: 371 questionnaires were returned (response rate 46%). 39% of
      the parents had had their daughters vaccinated. The main reasons for parents to
      decide not to participate in the vaccination programme were perceived dangers of
      the vaccine, the risk of minor or major side-effects, and perceived limited
      efficacy of the vaccine. Religious beliefs also played a limited, but
      statistically significant, role. Many parents found it difficult to decide
      whether to let their daughter participate in the vaccination programme.
      CONCLUSION: Follow-up research into participation is recommended, especially once
      health-education has been improved and media attention is reduced. Future
      communication about HPV vaccination should take into account the role played by
      parents in deciding whether or not to participate in the vaccination programme
      and should concentrate on their concerns about vaccine side-effects and vaccine
      safety and the perceived efficacy of the new vaccine.

PMID- 20699021
TI  - [Treatment of tension type headache: paracetamol and NSAIDs work: a systematic
      review].
AB  - OBJECTIVE: Tension-type headache (TTH), also known as tension headache or muscle
      contraction headache is the most commonly experienced type of headache. Our aim
      was to evaluate the effectiveness of interventions in patients with TTH. METHOD:
      We performed a systematic review according to the guidelines of the Cochrane
      Collaboration. Randomised trials reporting conservative treatments in patients
      with TTH with headache as outcome were included. In the analysis studies were
      grouped according to type of intervention: acute pain medication, preventive
      medication, physiotherapy interventions, behavioural interventions and
      interventions in children. RESULTS: A total of 152 trials were included in this
      review with 17.523 patients, of which 37 studies (24.3%) were considered to be of
      high quality. Nine studies could not be included in one of the five subgroups.
      ACUTE MEDICATION: (41 trials). The pooled analyses showed that NSAIDs and
      acetaminophen are more effective than placebo. No significant differences could
      be found between different types of NSAIDs, but ibuprofen showed fewer short-term
      side effects when compared to other NSAIDs. There was a significant difference in
      favour of NSAIDs when compared to acetaminophen. PREVENTIVE MEDICATION: (44
      trials). Overall, the use of antidepressants does not show to be more effective
      than placebo, and no significant differences between different types of
      antidepressants were found. Furthermore there is limited evidence concerning the
      negative effects of propranolol on depression in TTH patients, when compared to
      placebo or biofeedback. There is conflicting evidence about the effectiveness of
      benzodiazepines and vasodilator agents compared to placebo. There is no evidence
      concerning the effectiveness of muscle relaxants compared to placebo. BEHAVIOURAL
      THERAPY: (44 trials). Eight studies compared relaxation treatment with a waiting
      list or attention placebo control, and 11 studies compared EMG biofeedback with
      placebo and in both interventions we found inconsistent results. Most trials lack
      adequate power to show statistical significant differences, but frequently
      recovery/improvement rates did not reach clinical relevance. PHYSIOTHERAPEUTIC
      INTERVENTIONS: (12 trials). A wide variety of interventions were evaluated, such
      as spinal manipulations, exercise and physical applications. Overall the studies
      showed inconsistent results. CHILDREN: (11 trials). Eight studies evaluated the
      effectiveness of relaxation training. We found conflicting evidence for
      relaxation therapy compared with no treatment or other treatments. CONCLUSION:
      The evidence in this review suggests that NSAIDs and acetaminophen are both
      effective for short-term pain relief in patients with TTH. No specific type of
      NSAID was clearly more effective than others, but ibuprofen showed fewer side
      effects. There is insufficient evidence to either support or refute the
      effectiveness of preventive medication, physiotherapy, (spinal) manipulation, EMG
      biofeedback or cognitive behavioural treatment in patients with TTH.

PMID- 20699022
TI  - [Pathology also subject to RCTs].
AB  - Pathology is a diagnostic field and pathologists do not treat patients. It would
      at first seem that randomised controlled trials (RCTs) are not an option in this
      field. However, pathology is often the gold standard for diagnostics in RCTs and
      guidelines. With the arrival of new techniques in pathology diagnostics,
      particularly molecular techniques, it seems that more objective data can be
      collected. An RCT recently studied the effect of an electronic reminder for
      further diagnostics of Lynch syndrome, a hereditary disorder that the pathologist
      can detect by testing microsatellite instability. Studies to make pathology
      reporting more evidence-based are also very likely. Even the role of pathology in
      the diagnosis and treatment of patients needs to be made more verifiable.

PMID- 20699023
TI  - [A woman with a swollen finger].
AB  - A 70-year-old woman presented with osteomyelitis of the distal phalanx of her
      left middle finger, after a paronychia which was treated conservatively.

PMID- 20699024
TI  - [A woman with a blue coloured skin].
AB  - A 66-year-old woman with carcinoma of the breast developed a blue-grey colouring
      of the skin, after injection of patentblue for sentinel node procedure. This is a
      rare hypersensitivity reaction on patentblue, with the risk of depression of
      oxygen saturation or anaphylactic shock.

PMID- 20699025
TI  - [Delirium on intensive care frequently missed: clinical impression alone is not
      enough].
AB  - OBJECTIVE: To compare the sensitivity and specificity of a routine assessment
      (clinical impression) with a structured assessment which uses a validated
      assessment scale for the recognition of delirium on the intensive care unit
      (ICU). DESIGN: Observational study. METHOD: During their admission to the
      intensive care unit, 103 patients were assessed daily (with a maximum of 40 days)
      for the presence of delirium using the Confusion assessment method for the
      intensive care unit (CAM-ICU). Their physicians indicated whether or not they
      considered the patient delirious. These findings were compared. For all patients
      daily information was also collected about fixation and complications, such as
      self-extubation or self-removal of catheters. RESULTS: The patients were assessed
      for a period of 502 patient-days. CAM-ICU scores were positive (n = 108),
      negative (n = 235) or non-assessable because the patient was comatosed or deeply
      sedated (n = 159). The sensitivity of clinical detection by the physicians was
      45% in comparison to the CAM-ICU. The specificity was high (97%). CONCLUSION: The
      diagnosis delirium is frequently missed on the ICU when only based on clinical
      impression. Routine assessment using a validated assessment scale such as the CAM
      ICU might possibly improve this.

PMID- 20699026
TI  - [Genetic variations affect drug safety and efficacy].
AB  - Pharmacogenetics is a field that deals with the relationship between genetic
      variations and the effects and side-effects of drugs. Genetic variations in drug
      metabolizing enzymes, transporters, receptors, and other drug targets have been
      linked to interindividual differences in the efficacy and safety of many drugs.
      Genotyping is performed increasingly in primary and secondary health care in
      patients with abnormal plasma drug levels, in insufficient efficacy or in the
      presence of side-effects. Trastuzumab and abacavir are examples of drugs where
      patients are tested before treatment is started, in order to ascertain whether
      they carry a particular genetic variant. Trastuzumab is effective only when a
      particular protein is expressed in breast cancer tissue and the AIDS inhibitor
      may cause serious hypersensitivity reactions in patients carrying a particular
      variant. It is expected that screening for genetic variants prior to drug
      treatment will occur more often. This depends on the intensity of the association
      between genotype and outcome, the severity or relevance of the clinical outcome
      and the availability of alternative treatment.

PMID- 20699027
TI  - [Acute renal failure due to RAAS-inhibitors combined with dehydration].
AB  - Two men (61 and 81 years old) with mild impaired kidney function developed acute
      renal failure due to dehydration combined with the use of inhibitors of the renin
      angiotensin-aldosterone system (RAAS). After rehydration, correction of
      hyperkalaemia and stopping RAAS-inhibition and diuretics, they recovered
      completely. Many patients using RAAS-inhibitors have impaired renal function. In
      the case of dehydration due to gastroenteritis or prolonged fever they risk
      developing acute renal failure. The high risk groups are elderly patients,
      patients with atherosclerosis or heart failure and those with co-medication of
      diuretics or NSAIDs. The underlying mechanism is that the normal pathways to
      protect kidney perfusion in case of hypovolaemia are blocked by the use of RAAS
      inhibitors or NSAIDs. In the case of dehydration in patients with chronic kidney
      disease using RAAS-inhibitors, serum creatinine and potassium levels should be
      monitored. Temporary discontinuation of RAAS-inhibitors or diuretics is often
      necessary.

PMID- 20699028
TI  - [Serious gastrointestinal complications due to accidental ingestion of magnetic
      toy parts].
AB  - A 3-year-old boy presented at the emergency room with abdominal pain, nausea and
      non-bilious vomiting. Physical examination revealed moderate symptoms of
      dehydration, a tender and slightly extended but soft abdomen and active
      peristalsis. With the working diagnosis of viral gastroenteritis the boy was
      admitted to the hospital for rehydration therapy by nasogastric tube. After a few
      days an abdominal X-ray was taken because of bilious vomiting and persistent
      absence of defecation. Connected foreign bodies were seen in the small intestine.
      These appeared to be 3 magnetic toy parts. Laparotomy showed that all symptoms
      were due to a volvulus of the small intestine around a fistula caused by
      entrapment of the intestinal wall between attracted magnets. Magnetic
      construction toys can be bought in toy stores in the Netherlands. Vigilance
      should be exercised with magnetic toys, because ingestion of multiple magnets can
      cause potentially life-threatening bowel complications.

PMID- 20699029
TI  - [Percentage of local recurrence following treatment for breast cancer is not a
      suitable performance indicator].
AB  - OBJECTIVE: To describe the percentage of local recurrences within 5 years after
      surgery for breast cancer as a performance indicator for Dutch hospitals. DESIGN:
      Descriptive, cohort study. METHOD: All women diagnosed with a primary invasive
      breast cancer in 2003 for which they underwent curatively intended surgical
      treatment (with or without radiotherapy), were selected from the Netherlands
      Cancer Registry (NCR). NCR registration clerks collected additional information
      on recurrences within 5 years after initial diagnosis following standardized
      protocol. Percentages of local recurrences per hospital were estimated using
      Kaplan Meier analysis and were presented in forest plots and funnel plots.
      RESULTS: In 2003, 9898 women diagnosed with primary breast cancer were curatively
      treated in one of the 99 Dutch hospitals. 266 patients experienced local
      recurrences within 5 years. The 5-year percentage of local recurrences was 3.03%
      (95% CI: 2.69-3.41). Following breast conserving surgery the 5-year percentage of
      local recurrence was 2.63% (95% CI: 2.21-3.12), and following mastectomy 3.50%
      (95% CI: 2.97-4.13). Stratification by hospital shows large variation in
      recurrence rates (0-17%). However, the number of patients treated in most
      hospitals is too small to provide reliable estimates. CONCLUSION: The percentage
      of local recurrences following surgical treatment for breast cancer in the
      Netherlands was lower than the accepted standard of 5% within 5 years. Statements
      on differences in quality of care between hospitals cannot be made on the basis
      of these data, on account of the low average recurrence rate and the small number
      of cases per hospital.

PMID- 20699030
TI  - [Screening for chronic Q fever in symptomatic patients with an aortic aneurysm or
      prosthesis].
AB  - A 76-year-old man was referred to the Emergency Department because of collapse,
      epigastric pain and nausea. The patient had been diagnosed with an infrarenal
      aneurysm of the abdominal aorta nine years earlier. His symptoms were attributed
      to an aortic-duodenal fistula originating from the aneurysm. The patient died
      despite placement of an aortic prosthesis. A hospital screening programme for
      chronic Q fever in patients with aortic aneurysm revealed chronic Q fever. Until
      recently, vascular infection with Coxiella burnetii was an unknown disease in the
      Netherlands. In view of the nonspecific clinical presentation, severity and
      therapeutic consequences of the disease, we advise screening for chronic Q fever
      in all symptomatic patients with an aortic aneurysm or prosthesis - whether or
      not with aspecific symptoms - in regions where the disease is endemic.

PMID- 20699031
TI  - [Body donation versus organ donation].
AB  - There appears to be a discrepancy between the oversupply of donated bodies 'for
      science' in anatomical institutions in the Netherlands and the shortage of
      donated organs. However, organ donation is not as straightforward as it seems,
      mainly because of its strict conditions, e.g. with respect to age and the
      required hospital setting of the dying. Since Dutch body donors are mainly
      elderly men, their attitudes to their body, death and science should be explored
      from a generational perspective.

PMID- 20699032
TI  - [Migraine and depression should be treated concurrently].
AB  - Migraine and depression are highly prevalent disorders with a strong
      bidirectional comorbidity: migraine patients have an increased risk for
      depression and patients suffering from depression have an increased risk for
      migraine. This comorbidity could be due to an underlying common
      pathophysiological mechanism. Chronification of migraine further increases the
      chance of developing depression, and vice versa. Misuse of migraine attack
      medication plays an important role in the development of chronic migraine. It is
      important for general practitioners, psychiatrists and neurologists to be alert
      to the comorbidity of migraine and depression. It is recommended that different
      hospital specialists should be involved in both the diagnosis and treatment of
      patients with comorbidity of migraine and depression.

PMID- 20699033
TI  - [A boy with small lumps on his shoulder].
AB  - A 17-year-old boy presented with small papules on his right shoulder and was
      diagnosed with syringocystadenoma papilliferum.

PMID- 20699034
TI  - [Controversy surrounding the term 'retinal migraine'].
AB  - The term 'retinal migraine' is probably often wrongly applied. The primary reason
      for this is a confusion of nomenclature. No consensus exists in the neurological
      and ophthalmological literature on the diagnosis of 'retinal migraine'. A
      diagnosis of 'retinal migraine' should be avoided if no typical migraine headache
      is experienced following the visual symptoms. It is also a matter of debate
      whether retinal migraine can lead to permanent visual loss. If a patient
      complains of monocular visual loss, he or she may in fact have hemianopia.

PMID- 20699035
TI  - [Sylvius (1614-1672) and his fissure].
AB  - Franciscus dele Boe, or Sylvius, was born into a family of French Huguenots who
      had moved to the province of Hessen. He studied medicine in Sedan, Leiden and
      Basle. He was a private teacher in anatomy in Leiden for some years, and while
      teaching he drew the attention of his students to the long fissure on either side
      of the cerebral surface. He practised successfully as a physician in Amsterdam
      from 1641 onwards, until he was recalled to the chair of medicine in Leiden in
      1658. He emphasized the role of chemical processes in the human body
      (iatrochemistry).

PMID- 20699036
TI  - [Preventive treatment for migraine].
AB  - Migraine patients who experience an average of 2 or more attacks per month are
      eligible for preventive treatment as well as treatment for acute attacks. The
      decision to offer preventative treatment is also made on the basis of the average
      attack duration, severity of the attacks, and response to attack treatment. Prior
      to initiating preventive treatment, the average attack frequency per month should
      be assessed, preferably by means of a headache diary over a number of months, as
      attack frequency is extremely variable. None of the currently available
      preventive drugs, such as beta-blockers, sodium valproate, topiramate and
      candesartan, were developed specifically for treating migraine, but were all
      originally intended for other indications. 50% of the migraine patients receiving
      preventive treatment can expect a 50% reduction in attacks, and the remaining
      attacks often seem to be less severe. The effects of the drugs are often
      unpredictable per individual, and side-effects frequently lead to early
      discontinuation of treatment. Drugs usually prescribed for cardiovascular
      disorders are often used. In the case of a disorder such as migraine with a high
      burden of disability, patients with cardiovascular or pulmonary comorbidity
      should receive medication that is optimally adjusted for both indications.

PMID- 20699037
TI  - [Never too old for modern infarct-treatment].
AB  - In 4 elderly patients, two women aged 94 and 92 and two men aged 98 and 95 years,
      respectively, acute symptoms were found to be caused by acute myocardial
      infarction (AMI). The first woman and the two men were treated by stenting and/or
      percutaneous intervention and recovered fully, but in the second woman, who was
      hemiplegic following a CVA and had progressive dementia, a palliative treatment
      course was chosen after extensive consultation with the general practitioner and
      the next of kin. In elderly patients the outcome after AMI is often worse than in
      their younger counterparts. On the other hand, treatment decisions in elderly
      patients are often automatically considered to be difficult, which may result in
      under-treatment or no treatment at all. This has been referred to as
      discrimination towards the elderly. Primary angioplasty should not be withheld on
      the basis of age alone.

PMID- 20699038
TI  - [Preoperative biliary drainage for pancreatic head tumours: more complications]

PMID- 20699039
TI  - [Carcinoma of the head of the pancreas: indication for emergency surgery].
AB  - In a recent multicentre randomized clinical trial, Van der Gaag et al. randomly
      assigned 220 patients to early surgery or preoperative biliary drainage
      ('Preoperative drainage for cancer of the head of the pancreas'). The rate of
      serious complications was significantly higher in the preoperative drainage group
      (p < 0.001), mainly because of drainage-related complications. There was no
      difference in surgical complications or mortality. Data on costs and impact on
      quality of life were not presented, but it can be predicted that the preoperative
      drainage strategy would be more expensive and would have greater negative impact
      on quality of life. If forthcoming publications by this research group confirm
      this suggestion, the current paradigm - obstructive jaundice, endoscopic
      retrograde cholangiopancreatography with stenting, delayed surgery for carcinoma
      of the head of the pancreas - should be changed to: obstructive jaundice due to
      peri-ampullary carcinoma should be considered an indication for emergency
      surgery.

PMID- 20699040
TI  - [A premature neonate with a big belly].
AB  - A premature neonate, presenting with vomiting, abdominal distention and rectal
      blood loss, was found to have pneumatosis intestinalis on plain abdominal X-ray.
      These findings are indicative of necrotizing enterocolitis.

PMID- 20699041
TI  - [Tubulo-interstitial nephritis in inflammatory bowel disease: extra-intestinal
      manifestation or drug toxicity?].
AB  - Chronic inflammatory bowel disease (IBD) is seldom complicated by renal function
      disorder, but when this occurs the consequences are serious. In addition to the
      known effects of 5-aminosalicylates, there is also evidence that tubulo
      interstitial nephritis (TIN) occurs as an extra-intestinal manifestation of IBD.
      A 27-year-old woman with colitis ulcerosa, developed end-stage renal
      insufficiency due to a mesalazine-induced TIN. She was treated by haemodialysis
      for two years before she underwent renal transplantation. Another patient, a 36
      year-old man with Crohn's disease, developed extensive granulomatous nephritis
      with stable moderate renal function. After excluding other possible causes, we
      diagnosed an extra-intestinal manifestation of his Crohn's disease. There are no
      official guidelines on renal function monitoring in IBD patients, nor is there
      consensus in literature. We advise renal monitoring after three months of
      treatment with 5-aminosalicylates, followed by monitoring every year. Patients
      not receiving treatment should be monitored every year.

PMID- 20699042
TI  - [Acrodermatitis chronica atrophicans: late manifestation of Lyme borreliosis].
AB  - A 71-year-old man was referred to our outpatient clinic because of arthralgia and
      swelling of his right hand. He also showed a subcutaneous nodule on his left
      knee. A second patient, a 57-year-old woman, was referred because of painful skin
      of her legs. Dermatologic examination revealed erythematous livid discoloration
      on both feet and legs. There were reticular varices, corona flebectatia
      paraplantaris medialis and minimal pitting oedema. Serology tested positive in
      both patients for Borrelia and they both recalled tick bites. A third patient, a
      73-year-old woman, was referred because of erythema and maculae located at her
      lower legs and positive Borrelia serology. Pathologic examination was typical for
      acrodermatitis chronica atrophicans, a late skin manifestation of Lyme
      borreliosis. In all patients, symptoms improved after treatment with doxycycline
      for four weeks. A lack of familiarity with this skin condition may lead to
      unnecessary vascular investigations and considerable delay in adequate treatment.

PMID- 20699043
TI  - [Reduction in chronic pelvic pain in women with less catastrophizing pain]
AB  - OBJECTIVE: To evaluate the course of chronic pelvic pain (CPP) symptoms in women
      and to explore factors associated with changes in pain intensity and adjustment
      to pain in the long term. DESIGN: Follow-up study. METHOD: All women who had
      visited a Chronic Pelvic Pain team of a university hospital in the past were
      invited to participate. All completed a set of questionnaires at their first
      visit and follow-up. RESULTS: Of the 131 women who met the inclusion criteria, 84
      (64%) consented to participation in this follow-up study. After a mean follow-up
      period of 3 years, significant changes were found as regards a reduction in pain
      intensity, an improvement in adjustment to pain (i.e., physical well-being and
      depressive symptoms), a reduction in catastrophizing pain and an increase in
      perceived pain control. Neither sociodemographic, clinical nor pain-related
      variables were associated with these changes. Pain appraisals and pain coping
      strategies at baseline did not predict changes from baseline in pain intensity. A
      reduction in catastrophizing pain, however, was associated with a reduction in
      pain intensity and adjustment to pain, especially as regards physical well-being
      and depressive symptoms. CONCLUSION: After 3 years' follow-up, an improvement in
      pain intensity was observed in women with CPP, and this was not associated with
      baseline pain appraisals and coping strategies. A reduction in catastrophizing
      pain was related to better outcome in the long term.

PMID- 20699044
TI  - [Chronic abdominal complaints and perceptions].
AB  - A recent study by Weijenborg et al. on the progress of patients with abdominal
      complaints actually replicates in a gynaecological outpatient clinic an earlier
      study carried out in an internal medicine outpatient clinic. Both studies show
      that only 9% of the patients are symptom-free at follow up. Perceptions of the
      complaints seemed related to improvement. What can a physician do for these
      patients? It is known from other publications that correct perception by the
      physician of patients' somatic attributions and anxiety leads to a decrease at
      the next consultation. Reduced somatic attributions and anxiety are also
      favourable for the outcome at six months follow up: patients have less severe
      abdominal pain and less healthcare-seeking behaviour. The Weijenborg et al. study
      is therefore a useful repeat study and reiterates that physicians' behaviour can
      be helpful during consultations.

PMID- 20699045
TI  - [Cost-effectiveness of new drugs impacts reimbursement decision making but room
      for improvement].
AB  - OBJECTIVE: For new drugs to be included in appendix 1B of the drug reimbursement
      system, they must have proven added therapeutic value, an acceptable budget
      impact, and be cost-effective. To validate the latter, pharmacoeconomic
      evaluations have become mandatory. These evaluations should adhere to guidelines
      for pharmacoeconomic research. Our study evaluates: 1) the extent to which the
      pharmacoeconomic evaluations adherence pharmacoeconomic guidelines; 2) which
      guidelines are decisive in evaluating the validation of cost-effectiveness of new
      drugs; and 3) the impact of pharmacoeconomics in the recommendations and final
      decision making on drug reimbursement. DESIGN: Retrospective, descriptive study.
      METHOD: We examined all 1B requests for reimbursement submitted to the Dutch
      Health Care Insurance Board and the Medicinal Products Reimbursement Committee
      between 1 January 2005 and 30 September 2008, and on which recommendations on
      drug reimbursement have been published (n = 21). Data on adherence to guidelines,
      validation of cost-effectiveness, and recommendations and decision making on drug
      reimbursement were extracted from publicly available sources by two independent
      evaluators. Quantitatively and qualitatively descriptive analyses were carried
      out. RESULTS: Since pharmacoeconomic evaluations have become mandatory, these
      evaluations increasingly adhere to guidelines for pharmacoeconomic research. This
      was particularly true of the perspective chosen, the relevant treatment
      comparator and the incremental and total analyses of costs and effects of the
      drugs under comparison. However, cost-effectiveness of new drugs was often
      inadequately validated by incorrect indications for drug use, and incorrect forms
      of evaluation or periods of analysis. In addition, costs and effects were not
      always correctly analysed, nor and not enough insight was provided into the
      analysis model used. Partially on the basis of pharmacoeconomics, 12 new drugs
      are reimbursed and 9 not. CONCLUSION: Cost-effectiveness of new drugs and more
      valid pharmacoeconomic evaluations appear to play an ever more important role in
      reimbursement decision making and the pursuit of better and affordable health
      care.

PMID- 20699046
TI  - Microlinguistic aspects of the oral narrative in patients with Alzheimer's
      disease.
AB  - BACKGROUND: Alzheimer's disease (AD) is characterized by memory loss and
      cognitive impairment. Phonological, syntactic, semantic and discursive aspects of
      language may also be affected. Analysis of micro- and macrolinguistic abilities
      of discourse may assist in diagnosing AD. The aim of this study was to identify
      changes in the discourse (lexical errors and syntactic index) of AD patients.
      METHODS: 121 elderly subjects narrated a story based on a seven-figure picture
      description. RESULTS: Patients with AD presented more word-finding difficulties,
      revisions and repetitions, and the syntactic index was lower than controls.
      CONCLUSION: Performance in microlinguistics at the lexical and syntactic levels
      was lower than expected in participants with AD.

PMID- 20699047
TI  - Social vulnerability and prefrontal cortical function in elderly people: a report
      from the Canadian Study of Health and Aging.
AB  - BACKGROUND: Prefrontal cortical lobe function is related to social behavior in
      humans. We investigated whether performance on tests of prefrontal cortical
      function was associated with social vulnerability. Associations with non-frontal
      cognitive function were investigated for comparison. METHODS: 1216 participants
      aged 70+ of the Canadian Study of Health and Aging-2 screening examination, who
      also underwent detailed neuropsychological testing, comprised the study sample.
      Performance on WAIS-R abstraction, WAIS-R comprehension, Trails B, FAS and
      category verbal fluency, Block construction, Token Test and Wechsler Memory Scale
      Information Subset was tested in relation to the participant's level of social
      vulnerability using regression models adjusted for age, education, sex, frailty,
      MMSE score, diagnosis of depression, and use of psychoactive medications. Social
      vulnerability was measured by an index comprising many social problems or
      "deficits". RESULTS: The most socially vulnerable group had worse performance on
      FAS verbal fluency, generating 4.1 fewer words (95% CI: 1.8-6.4, p<0.001) than
      those in the least socially vulnerable group; those with intermediate social
      vulnerability generated 2.6 fewer words (95% CI: 0.4-4.8, p = 0.02). Social
      vulnerability was also associated, though less strongly, with category verbal
      fluency. The most socially vulnerable people had impaired performance on the
      Trails B, taking 37 seconds longer (95% CI: 11-63, p = 0.005). These results were
      independent of age, education, sex, frailty, MMSE score, depression, and
      psychoactive medications. Social vulnerability was not associated with
      performance on WAIS-R abstraction, WAIS-R comprehension, Block Design, Token Test
      or Wechsler Memory Scale tests. CONCLUSIONS: High social vulnerability was
      associated with impaired performance on verbal fluency and set shifting but not
      with common sense judgment, abstraction, long-term memory, constructional
      ability, or language comprehension. The association between social functioning
      and the cognitive functions subserved by prefrontal cortex warrants further
      study.

PMID- 20699048
TI  - Optimizing mental health in long-term care homes.

PMID- 20699053
TI  - Idiopathic retroperitoneal fibrosis of the pancreas versus pancreatic carcinoma.
AB  - We report one of few cases of idiopathic retroperitoneal fibrosis of the
      pancreas, which is different from the classical retroperitoneal fibrosis that
      affects ureters and vessels that mimicking locally advanced pancreatic carcinoma
      at presentation.

PMID- 20699054
TI  - Chyle leak following laparoscopic cholecystectomy: a rare complication.
AB  - Gallstone disease is a highly prevalent condition which is commonly and safely
      treated by laparoscopic cholecystectomy. We present the third reported case of
      chyle leakage following laparoscopic cholecystectomy in the setting of acute
      cholecystitis. The report reviews current literature on the prevalence, diagnosis
      and management of this condition.

PMID- 20699055
TI  - Colon perforation secondary to porphyria.
AB  - Acute intermittent porphyria (AIP) is a rare, inherited metabolic disorder of the
      haem biosynthesis pathway. The diagnosis is well known to cause significant
      diagnostic challenge due to its broad range of symptoms that may mimic many other
      conditions. We report a case of AIP that presented with caecal perforation, a
      clinical scenario that has not previously been reported in the literature.

PMID- 20699056
TI  - Clarification of the blood compatibility mechanism by controlling the water
      structure at the blood-poly(meth)acrylate interface.
AB  - In previous studies, we reported that poly(2-methoxyethyl acrylate) (PMEA)
      exhibited excellent blood compatibility, although it has a simple chemical
      structure. Since then, we have been investigating the reasons for its blood
      compatibility. In this short review, we consider the reasons for this
      compatibility by comparing the structure of water in hydrated PMEA to the water
      structure of poly(2-hydroxyethyl methacrylate) (PHEMA) and poly(meth)acrylate
      analogs as reference polymers. The hydrated water in PMEA could be classified
      into three types; free water (or freezing water), freezing-bound water (or
      intermediate water), and non-freezing water (or non-freezing-bound water). We
      found that hydrated PMEA possessed a unique water structure, observed as cold
      crystallization of water in differential scanning calorimetry (DSC). Cold
      crystallization is interpreted as ice formation at low temperature, an attribute
      of freezing-bound water in PMEA. The cold crystallization peak was observed for
      hydrated poly(ethylene glycol) (PEG), poly(vinyl methyl ether) (PVME),
      polyvinylpyrrolidone (PVP), poly(2-methacryloyloxyethyl phosphorylcholine)
      (PMPC), poly(tetrahydrofurfuryl acrylate) (PTHFA), and newly synthesized poly(2
      (2-ethoxyethoxy)ethyl acrylate), as well as various proteins and polysaccharides,
      which are well-known biocompatible polymers. On the other hand, cold
      crystallization of water was not observed in hydrated PHEMA and PMEA analogous
      polymers, which do not show excellent blood compatibility. Based on these
      findings, we hypothesized that freezing-bound water, which prevents the
      biocomponents from directly contacting the polymer surface or non-freezing water
      on the polymer surface, plays an important role in the excellent blood
      compatibility of PMEA.

PMID- 20699057
TI  - Active targeting behaviors of biotinylated pluronic/poly(lactic acid)
      nanoparticles in vitro through three-step biotin-avidin interaction.
AB  - In order to prepare targeted drug carriers, previously a biotin group has been
      attached by our group to the end of Pluronic F87/poly(lactic acid) and Pluronic
      P85/poly(lactic acid) block co-polymers to obtain B-F87-PLA and B-P85-PLA,
      respectively. In this paper, the active targeting properties of B-F87-PLA and B
      P85-PLA nanoparticles in vitro were investigated through a three-step biotin
      avidin interaction by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium
      bromide (MTT) tests and fluorescence microscopy (FM). Two kinds of human ovarian
      cancer cells (OVCAR-3 and SKOV-3) and paclitaxel were chosen for the cytotoxicity
      tests. CA-125 antigen is over-expressed on OVCAR-3 cells but not on SKOV-3 cells.
      The loading and release behavior of paclitaxel loaded in B-Pluronic-PLA
      nanoparticles were also studied. Paclitaxel loaded in both B-F87-PLA and B-P85
      PLA nanoparticles shows an initial rapid release followed by a slow release
      period. Compared with SKOV-3 cells, the cytotoxicity results implied that
      paclitaxel-loaded B-Pluronic-PLA nanoparticles were delivered more effectively to
      OVCAR-3 cells due to the specific interaction between the biotin groups on the
      surface of B-Pluronic-PLA nanoparticles and the avidin/biotinylated MAb X306/CA
      125 antigen complexes on the surface of OVCAR-3 cells. The active targeting
      properties of B-F87-PLA nanoparticles were further confirmed by FM.

PMID- 20699058
TI  - Interactions between bovine serum albumin and oxidized sodium alginate in
      solution.
AB  - This paper focuses on the interactions between oxidized sodium alginate (OSA) and
      bovine serum albumin (BSA) at the molecular level with the purpose to provide
      basic information for optimizing the biological utilization and pharmaceutical
      applications of OSA. The results revealed that OSA could strongly quench the
      intrinsic fluorescence of BSA through a static quenching procedure. The
      thermodynamic parameters, enthalpy change (DeltaH) and entropy change (DeltaS),
      were also calculated. The process of binding was a spontaneous process in which
      Gibbs free energy change was negative. The distances between donor (BSA) and
      acceptor (OSA) were calculated to be 2.41, 2.54 and 2.84 nm for SA-BSA, 10% OSA
      BSA and 30% OSA-BSA systems, based on Forster non-radiative energy transfer
      theory, respectively. The results of synchronous fluorescence spectra showed that
      binding of OSA with BSA cannot induce conformational changes in BSA. Meanwhile,
      the OSA with low degree of oxidization (DO% <= 30%) was non-cytotoxic. Therefore,
      OSA could be promising as a bioactive compound carrier.

PMID- 20699059
TI  - alpha- and beta-poly(vinylidene fluoride) evoke different cellular behaviours.
AB  - alpha-Phase poly(vinylidene fluoride) (PVDF) has chains of zero dipole moments
      and is, therefore, nonpiezoelectric, while beta-phase PVDF has the most
      significant piezoelectric properties among the polymorphs due to its polar
      chains. Although many reports describe PVDF as a suitable biomaterial due to its
      stability and biocompatibility, few considered the specific effects that the
      different polymorphs exert on cellular behaviour. We hypothesized that alpha- and
      beta-phase PVDF will exert direct but different influences on cell attachment and
      metabolic activity. PVDF films were fabricated using N,N-dimethylformamide (DMF)
      and hexamethylphosphoramide (HMPA) by solvent casting. Samples were characterized
      by differential scanning calorimetry, Fourier transform infrared spectroscopy and
      X-ray diffraction. Films containing 83.5% alpha-phase PVDF (DMF-PVDFalpha) and
      91.4% of beta-phase PVDF (HMPA-PVDFbeta within the crystalline regions were
      produced and used to evaluate in vitro attachment and metabolic activity of L929
      cells. Cell metabolic activity on both PVDF conformations increased 3-fold over
      the 1-week culture period, with higher cell metabolic activity observed on DMF
      PVDFalpha on day 5 of culture, compared to HMPA-PVDFbeta. Cells grown on DMF
      PVDFalpha were well-spread, flat and expressed spotted paxillin in focal
      adhesions that were mainly localized to perinuclear regions of the cells, while a
      high proportion of cells on HMPA-PVDFbeta were bulging, round and expressed
      relatively fewer paxillin spots. Our results suggest that alpha-phase PVDF
      supports higher cell metabolic activity and better cell spreading compared to
      beta-phase PVDF. Such variations can potentially be exploited for different
      biomedical applications.

PMID- 20699060
TI  - A biodegradable and biocompatible drug-delivery system based on polyoxalate
      microparticles.
AB  - Drug delivery using biodegradable polymeric microparticles is becoming an
      important means of delivering therapeutic agents. In this work, we describe
      polyoxalate microparticles as a biodegradable and biocompatible protein drug
      delivery system. Polyoxalate was synthesized from a polycondensation reaction
      between oxalyl chloride and 1,4-cyclohexanedimethanol under basic conditions.
      Polyoxalate, in design, undergoes hydrolytic degradation to generate non-toxic
      low-molecular-weight compounds that can be easily excreted from a body.
      Polyoxalate was hydrophobic and had a half-life of 6.5 days at pH 7.4. This
      hydrophobic polyoxalate could be formulated into microparticles by a double
      emulsion method and encapsulate proteins with a loading efficiency of more than
      80%. Cytotoxicity evaluation using RAW 264.7 cells indicated that polyoxalate
      microparticles exhibited a cytotoxicity profile superior to PLGA microparticles.
      The polyoxalate microparticles were taken up by macrophages in vitro as confirmed
      by confocal fluorescence microscopy. The ease of synthesis coupled with the
      physicochemical properties and excellent biocompatibility make this polyoxalate a
      promising candidate for protein-delivery applications.

PMID- 20699063
TI  - Population aging and the use of office-based physician services.
AB  - KEY FINDINGS: From 1998 to 2008, the proportion of physician office-based visits
      in the United States became increasingly concentrated on those aged 45 and over.
      The intensity of physician office visits, as measured by medications prescribed
      or continued, imaging tests ordered or provided, and time spent with physicians,
      also became increasingly concentrated on those aged 45 and over. Although most
      physicians accept Medicare patients, acceptance of Medicare was higher among
      ophthalmologists and general surgeons than among general or family practitioners,
      internists, and psychiatrists. Over the past 30 years, the specialty
      concentration of visits has shifted significantly. In 1978, 62 percent of visits
      by patients aged 65 and over were to primary care physicians compared with 45
      percent in 2008. The percentage of visits to physicians with a medical or
      surgical specialty increased from 37 percent to 55 percent.

PMID- 20699061
TI  - Gelatinized copper-capillary alginate gel functions as an injectable tissue
      scaffolding system for stem cell transplants.
AB  - In severe hypoxic-ischemic brain injury, cellular components such as neurons and
      astrocytes are injured or destroyed along with the supporting extracellular
      matrix. This presents a challenge to the field of regenerative medicine since the
      lack of extracellular matrix and supporting structures makes the transplant
      milieu inhospitable to the transplanted cells. A potential solution to this
      problem is the use of a biomaterial to provide the extracellular components
      needed to keep cells localized in cystic brain regions, allowing the cells to
      form connections and repair lost brain tissue. Ideally, this biomaterial would be
      combined with stem cells, which have been proven to have therapeutic potentials,
      and could be delivered via an injection. To study this approach, we derived a
      hydrogel biomaterial tissue scaffold from oligomeric gelatin and copper-capillary
      alginate gel (GCCAG). We then demonstrated that our multipotent astrocytic stem
      cells (MASCs) could be maintained in GCCAG scaffolds for up to 2 weeks in vitro
      and that the cells retained their multipotency. We next performed a pilot
      transplant study in which GCCAG was mixed with MASCs and injected into the brain
      of a neonatal rat pup. After a week in vivo, our results showed that: the GCCAG
      biomaterial did not cause a significant reactive gliosis; viable cells were
      retained within the injected scaffolds; and some delivered cells migrated into
      the surrounding brain tissue. Therefore, GCCAG tissue scaffolds are a promising,
      novel injectable system for transplantation of stem cells to the brain.

PMID- 20699064
TI  - [Level of evidence for therapeutic drug monitoring of cisplatin].
AB  - Cisplatin is an anticancer agent widely used in clinical practice. Cisplatin
      undergoes irreversible protein binding in plasma and presents a major
      nephrotoxicity. Some studies determined unbound and bound platin concentrations
      using flameless atomic absorption spectrophotometry or chromatography. These
      studies showed a relationship between cisplatin exposition, notably its maximal
      concentration, and nephrotoxicity. However, the relationship between cisplatin
      exposition and its efficacy is not yet established. The population approach using
      a nonlinear mixed effects model showed a low variability of drug exposition
      parameters. In some cases, Bayesian adaptative dosing were proposed. However,
      some particular populations will have to be taken into account such as children,
      elderly patients, acute or chronic renal failure. The impact of cisplatin
      pharmacogenetics on its therapeutic monitoring need to be studied. Therapeutic
      cisplatin monitoring is today possibly useful measuring maximal concentration and
      using described adjusted-modelling. Some prospective multicentric validations are
      required.

PMID- 20699065
TI  - [Level of evidence for therapeutic drug monitoring of carboplatin].
AB  - Carboplatin is an anticancer agent widely used in different types of cancer in
      adults and paediatrics patients. Carboplatin undergoes an high protein binding
      percentage in plasma and presents a major hematotoxicity. Some studies determined
      unbound and bound platin concentrations using flameless atomic absorption
      spectrophotometry or chromatography. These studies showed a relationship between
      carboplatin exposition expressed using AUC of ultrafiltrable concentrations with
      time and myelotoxicity. However, the relationship between carboplatin exposition
      and its efficacy is not yet established. The population approach using a
      nonlinear mixed effects model showed a low variability of drug exposition
      parameters. In some cases, Bayesian adaptative dosing were proposed. However,
      some particular populations will have to be taken into account such as intensive
      doses of carboplatin, children, patients with hemodialysis-dependent renal
      insufficiency or obese patients. Therapeutic carboplatin monitoring is today
      recommended measuring AUC ultrafiltrable concentrations in time and using
      described adjusted-modelling.

PMID- 20699066
TI  - [Therapeutic drug monitoring of methotrexate after its administration in high
      dose protocols].
AB  - After HD-MTX infusions, i.e. at a dose>1 g/m2, monitoring of serum MTX
      concentrations is a standard practice which helps reducing the incidence of
      toxicity in patients with decreased clearance by guiding dose adjustment of
      leucovorin. Therapeutic monitoring of methotrexate is based on iterative
      measurements of serum concentration until concentration is below a certain
      threshold. This practice is supported by numerous observations of exposure
      related toxicity as well as some clinical studies comparing drug exposure between
      patients with and without toxicity. Despite no prospective clinical study has
      clearly demonstrated the usefulness of methotrexate TDM, historical comparison
      reveals a huge reduction of toxicity-related events over past decades. Systematic
      monitoring may also help identifying patients with abnormally high methotrexate
      concentrations, who require immediate treatment with carboxypeptidase.

PMID- 20699067
TI  - [Therapeutic drug monitoring of 5-fluorouracil after its administration in high
      dose protocols].
AB  - Therapeutic drug monitoring is currently investigated in patients receiving the
      drug by prolonged continuous infusion, either alone or associated with other
      chemotherapy agents. This arises from an increasing body of evidence that relates
      plasma fluorouracil concentrations to toxicity or effectiveness. Literature data
      indicate that threshold levels of exposure, as assessed by the area under the
      concentration-time curve, are associated with an increased risk of toxicity in
      patients treated for either a colorectal or a head and neck cancer. Kinetically
      guided dose adjustment may thus be proposed for the ongoing or the next cycle of
      chemotherapy. Historical comparisons and the results of a phase III multicenter
      randomized study in patients with metastatic colorectal cancer showed that dose
      adapted fluorouracil resulted in significantly improved objective response rate,
      a trend to higher survival rate and fewer grade III-IV toxicities. Real-time
      fluorouracil monitoring may also help identifying patients with higher than
      expected exposure, thus providing a basis for intensifying supportive care in
      these patients.

PMID- 20699069
TI  - [Therapeutic drug monitoring of 6-thioguanine nucleotides in paediatric acute
      lymphoblastic leukaemia: interest and limits].
AB  - 6-mercaptopurine, a key drug for the treatment of acute lymphoblastic leukaemia
      in children, is a prodrug metabolized into 6-thioguanine (6-TGN) which are the
      active compounds and into methylated metabolites, primary by thiopurine S
      methyltransferase enzyme (TPMT). This enzyme displays important inter subject
      variability linked to a genetic polymorphism: when treated with standard doses of
      thiopurine, TPMT-deficient and heterozygous patients are at great risk for
      developing severe and potentially life-threatening toxicity (hematopoietic,
      hepatic, mucositis...) but show a better survival rate while patients with high
      TPMT activity (wild type) present lower peripheral red blood cells 6-TGN
      concentrations and a higher risk of leukemia relapse. Genotyping remains crucial
      before 6-MP administration at diagnosis to identify patients with homozygous
      mutant TPMT genotype and therefore prevent severe and life-threatening toxicity,
      and to individualize therapy according to TMPT genotype. Follow-up of ALL
      treatment should preferentially be based on repeated determinations of
      intracellular active metabolites (6-thioguanine nucleotides) and methylated
      metabolites in addition to haematological surveillance.

PMID- 20699068
TI  - [Therapeutic drug monitoring of 6-thioguanine nucleotides in inflammatory bowel
      disease: interest and limits].
AB  - Azathioprine, 6-mercaptopurine, and 6-thioguanine are immunosuppressive drugs
      indicated in the prevention of graft rejection, and treatment of auto-immune
      disease or inflammatory bowel disease. Their anti-nucleotidic properties are also
      used for the treatment of acute leukaemia. Their metabolism involves thiopurine
      methyl transferase, which activity varies according to genetic polymorphisms. In
      inflammatory bowel disease patients, there is no recommended therapeutic range of
      intra-erythrocyte 6-thioguanine nucleotide concentration, the active metabolite.
      Therapeutic drug monitoring of 6-thioguanine nucleotide concentrations is however
      proposed in the following clinical situations: to check the observance, to try to
      explain therapeutic failure, to manage patients with limited thiopurine methyl
      transferase activity or patients treated with associated drugs that can modify
      thiopurine methyl transferase activity. The literature review shows that high
      concentrations of 6-thioguanine nucleotides and methylated metabolites are
      associated with an increased risk of bone marrow toxicity. In addition, high
      concentrations of methylated metabolite might increase the risk of hepatic
      toxicity. These major side-effects can be prevented by the use of pre-treatment
      screening for thiopurine methyl transferase activity or genotype in inflammatory
      bowel disease patients in order to propose an adapted dosing.

PMID- 20699070
TI  - [Level of evidence for therapeutic drug monitoring for paclitaxel].
AB  - Paclitaxel is an anticancer drug which displays pharmacokinetic properties which
      can lead to therapeutic drug monitoring requirement. The most effective
      pharmacokinetic parameter seems to be the time during which the plasma
      concentration is over 0.05 micromol/L. However, this target needs to be validated
      with new weekly schedules of administration. These reasons lead to consider the
      level of evidence of therapeutic drug monitoring of paclitaxel as potentially
      useful.

PMID- 20699071
TI  - [Level of evidence for therapeutic drug monitoring for docetaxel].
AB  - Pharmacokinetic properties of docetaxel, an anticancer drug, are though to be
      interesting for therapeutic drug monitoring: high inter- and intra-variability,
      relationship between exposure and efficacy and especially toxicity. Moreover, the
      3-weekly administration, which is the more effective scheme, is also the more
      toxic. However, neutropenia can be modeled and be efficiently predicted without
      needing plasma drug concentrations. The level evidence of therapeutic drug
      monitoring is thus weak regarding the possibility to adapt dose regimen without
      drug concentrations.

PMID- 20699072
TI  - [Level of evidence for therapeutic drug monitoring for etoposide after oral
      administration].
AB  - Oral etoposide displays high inter- and intra-variability. Convincing
      relationships were observed between hematological toxicities and exposure of
      which total etoposide area under the curve seems the more relevant in routine
      practice. Linear pharmacokinetics, limited sampling strategies and reduction of
      variability during concentration-controlled studies argue in favor of therapeutic
      drug monitoring. For these reasons, such practice can be considered as
      recommended or potentially useful. Further studies using Bayesian approach are
      nevertheless needed to definitely state regarding the level of evidence
      therapeutic drug monitoring of oral etoposide.

PMID- 20699073
TI  - [Therapeutic drug monitoring of tyrosine-kinase inhibitors in the treatment of
      chronic myelogenous leukaemia: interests and limits].
AB  - During the last decade, imatinib was current gold standard treatment of chronic
      myelogenous leukemia (CML), showing a great effectiveness. Thus, the Therapeutic
      Drug Monitoring (TDM), rarely applied in clinical oncology practice, did not
      appear necessary at the moment. However, the absence of response among patients
      and the metabolic profile of imatinib (involving the CYP3A4) suggested the
      existence of a great interindividual variability. During the last 4 years,
      studies about the pharmacokinetic/pharmacodynamic relationship have confirmed
      this variability and highlighted a relation between the trough concentrations of
      imatinib and the clinical response. An effectiveness threshold, close to 1000
      ng/mL, seems to be correlated with better cytogenetic and molecular responses.
      Consequently, TDM could assist in investigation of the observance, the absence of
      response, the drug-drug interactions, but the proof of its utility requires
      complementary studies. In conclusion, the level of proof of imatinib TDM in LMC
      varies between levels "recommended" and "potentially useful".

PMID- 20699074
TI  - [Therapeutic drug monitoring of clonazepam].
AB  - Clonazepam is a 1-4 benzodiazepine mainly used to treat epilepsy and epileptiform
      convulsion state. Rapidly absorbed after oral administration, it is widely
      distributed in the organism and is extensively converted in metabolites, poorly
      or not active, eliminated mainly in urine (70%) and feces. Elimination half-life
      is long, around 40 h. In adult and child, several studies showed a concentration
      effect relation. Meanwhile, a large inter-individual variability in the dose
      concentration relation was observed. A 15-50 microg/L range of clonazepam blood
      concentrations appears to be retained as an acceptable target to control a
      majority of epileptic seizures. The Therapeutic Drug Monitoring (TDM) of
      clonazepam can be considered as possibly useful in case of association with
      CYP450 inducers or inhibitors, suspicion of poor observance, or toxicity signs.

PMID- 20699075
TI  - [Therapeutic drug monitoring of clobazam].
AB  - Clobazam is a 1,5 benzodiazepine available in France since 1975, used in add-on
      with the other anticonvulsant drugs in the treatment of refractory epilepsies of
      child and adult and for the treatment of anxiety of adult. It is mainly
      metabolized in desmethylclobazam, or norclobazam, active metabolite, present in a
      concentration approximately eight times superior to that of the parent drug, but
      with an activity of the order of 20 to 40% of that of clobazam. Elimination half
      life of clobazam is of 18 h while that of norclobazam is from 40 to 50 h. There
      is a large interindividual variability in the plasma concentrations. Furthermore,
      clobazam being prescribed in add-on with the other anticonvulsant drugs in
      resistant epilepsies, concentration-effect relationship is difficult to bring to
      light, since, in many studies, the patients who did not answer received the
      highest doses. Adverse reactions are moderated, appearing more often for the
      highest concentrations; also the phenomenon of tolerance seems more frequent in
      high concentrations. However, because of the kinetic interactions, a dosage of
      clobazam and norclobazam can be useful in certain cases. There is no validated
      therapeutic range, but the usual concentrations are in the range of 100-300
      microg/L for the parent drug and about ten times more for the metabolite. The
      level of proof of the interest of the Therapeutic Drug Monitoring for this
      molecule is estimated in: rather useless.

PMID- 20699076
TI  - [Therapeutic drug monitoring of valproate].
AB  - Valproic acid is an anticonvulsant drug available in France since 1967. It is a
      broad spectrum molecule indicated in various forms of epilepsy of the adult and
      the child, but it is also prescribed in the treatment of different other
      pathologies of nervous system. The divalproate sodium is indicated in the
      treatment of bipolar disorders. The valproic acid is marketed under various
      pharmaceutical forms, with different corresponding tmax values. But, whatever the
      administered preparation, the circulating active molecule is the ion valproate.
      Elimination half-life is from 11 to 20 h. Metabolization of valproate is
      important and represents its main route of elimination. Valpromide is comparable
      to a prodrug which metabolizes in valproate. The inter and intraindividual
      variability of the plasma concentrations are important. Several studies show a
      concentration-effect relationship, but two interventional trials ended in the
      lack of interest of the Therapeutic Drug Monitoring (TDM), although it is of
      current practice. However, numerous drug interactions may modify the plasma
      concentrations of valproate. The therapeutic range is from 50 to 100 mg/L (346
      693 micromol/L). The level of proof of the interest of the TDM for this molecule
      was estimated in: recommended.

PMID- 20699077
TI  - [Buprenorphine for the treatment of opioid dependence: a study on generic
      substitution conducted in community pharmacies].
AB  - OBJECTIVE: To describe the evolution of buprenorphine prescription form
      characteristics before and after the application of a measure of the French
      Social Security system aimed to encourage the use of generic drugs. METHOD: All
      buprenorphine prescription forms issued to sixty-two patients subjected to follow
      up in 6 community pharmacies were analysed between October 2007 and February
      2008. RESULTS: Patients maintained on Subutex during the whole follow-up were
      more numerous (n=39), younger, and received a higher daily dose of buprenorphine
      (10.5 mg versus 7.8 mg), compared to patients maintained on generic (n=13). For
      patients receiving again Subutex after have been treated by a generic (n=10),
      daily doses remained unchanged. CONCLUSION: It seems that the patients stabilized
      on generic present less serious pharmacodependence and less psychiatric
      comorbidity than those maintained on Subutex. Substituting a buprenorphine
      speciality with another should not induce any treatment unsettlement.

PMID- 20699078
TI  - [Drug induced colitis: review article].
AB  - Frequency of colitis induced by drugs is often under estimated. Antibiotics and
      nonsteroidal anti-inflammatory drugs (NSAIDS) are usually incriminated. In this
      study, we classified colitis according to the main responsible drug with a focus
      on clinical symptomatology, physiopathology, evolution, and complications. We
      describe colitis due to antibiotics, NSAIDS, laxatives, vasoconstrictive agents,
      oestroprogestatives, chemotherapy and drugs induced microscopic colitis. The last
      one represents a particular case; it can be idiopathic, infectious or drugs
      induced. Its physiopathology is not well known and its diagnosis is based only on
      histologic criterion. Drug responsibility is easy to determine only for
      pseudomembranous colitis. In the other cases, chronology is very variable and the
      clinical, endoscopic and histological elements are rarely specific. Because of
      the large number of drugs that may induce colitis, it is necessary to search for
      potentially responsible drugs, especially if there is no obvious cause of the
      colitis.

PMID- 20699079
TI  - Comparison of adverse drug reactions with donepezil versus memantine: analysis of
      the French Pharmacovigilance Database.
AB  - BACKGROUND: Since donepezil and memantine are currently used for treating
      Alzheimer's disease, it is interesting to analyse, reassess and compare their
      safety profile in order to promote a better use. METHODS: All spontaneous reports
      of suspected serious adverse drug reactions with donepezil alone and with
      memantine alone recorded in the French Pharmacovigilance Database during 6 years
      were retrospectively analysed. RESULTS: The most frequent adverse drug reactions
      with donepezil alone and memantine alone were respectively: bradycardia (10%
      versus 7%), weakness (5% versus 6%) and convulsions (4% versus 3%). CONCLUSION:
      The most adverse drug events with donepezil and with memantine are associated
      with elderly people, even if they do not receive any other treatment. Donepezil
      and memantine have an acceptable safety profile but physicians should take
      special care when they prescribe any drug known to cause bradycardia or to reduce
      the epileptogenic threshold.

PMID- 20699080
TI  - [Quantification of the part allocated to the preventability of vitamin K
      antagonists therapy bleeding events].
AB  - A prospective cohort of patients with a high INR (>or=5) and being treated by
      vitamin K antagonists (VKA) was assessed in the Amiens University Hospital. One
      of the purposes of the study was to assess the preventability of the haemorrhages
      due to VKA. The preventability concept is not very used in France. Identifying
      the preventability part of a side effect of a drug needs an adapted and reliable
      tool. Although different methods of assessment of preventability have been
      developed, none of them is unquestionable. For the needs of our study, we built a
      scale of measure adapted from a scale of preventability already published by
      defining more accurately some items and by reducing the subjective part of the
      interpretation. We were able to confirm the relevance of our revised scale by
      testing it by two experts. After consensus on the conflicting data, two thirds of
      the severe bleedings were considered as "potentially or totally preventable".
      These data are in agreement with published data. Indeed the data found in the
      literature are concordant to consider that an important part of VKA bleedings
      events can be prevented by a better management of the treatment.

PMID- 20699083
TI  - [One case report of a late cardiotoxicity after administration of low doses of
      anthracyclines].

PMID- 20699084
TI  - [Evaluation of antifungal activity of Mitracarpus scaber, a rubiaceae MISCA
      codified on Candida glabrata].

PMID- 20699085
TI  - Expression, purification, stability optimization and characterization of human
      Aurora B kinase domain from E. coli.
AB  - Aurora B kinase plays a critical role in regulating mitotic progression, and its
      dysregulation has been linked to tumorigenesis. The structure of the kinase
      domain of human Aurora B and the complementary information of binding
      thermodynamics of known Aurora inhibitors is lacking. Towards that effort, we
      sought to identify a human Aurora B construct that would be amenable for large
      scale protein production for biophysical and structural studies. Although the
      designed AurB(69-333) construct expressed at high levels in Escherichia coli, the
      purified protein was largely unstable and prone to aggregation. We employed
      thermal-shift assay for high-throughput screening of 192 conditions to identify
      optimal pH and salt conditions that increased the stability and minimized
      aggregation of AurB(69-333). Direct ligand binding analyses using temperature
      dependent circular dichroism (TdCD) and TR-FRET-based LanthascreenTM binding
      assay showed that the purified protein was folded and functional. The affinity
      rank-order obtained using TdCD and LanthascreenTM binding assay correlated with
      enzymatic IC50 values measured using full-length Aurora B protein for all the
      inhibitors tested except for AZD1152. The direct binding results support the
      hypothesis that the purified human AurB(69-333) fragment is a good surrogate for
      its full-length counterpart for biophysical and structural analyses.

PMID- 20699086
TI  - Spectroscopic studies of molecular organization of antibiotic amphotericin B in
      monolayers and dipalmitoylphosphatidylcholine lipid multibilayers.
AB  - Amphotericin B (AmB) is considered the gold-standard in the treatment of serious
      systemic mycoses despite its numerous adverse effects. Both the mechanism of
      antifungal action and the toxicity of this drug are dependent on its molecular
      organization. The effect of AmB on the organization of lipid membranes formed
      with dipalmitoylphosphatidylcholine (DPPC) was studied with application of the
      Langmuir-Blodgett technique and ATR-FTIR spectroscopy. The aim of this research
      was to analyze the physical interactions leading to the formation of aggregated
      forms of AmB molecules in one-component monolayers and lipid multibilayers.
      Analysis of FTIR spectra of two-component multibilayers suggests the possibility
      the mutual reorientation of the amino-sugar moiety (mycosamine) and macrolide
      ring. This effect may be significant in the explanation of the aggregation
      processes of AmB in biological systems.

PMID- 20699087
TI  - Role of monoamine oxidase, nitric oxide synthase and regional brain monoamines in
      the antidepressant-like effects of methylene blue and selected structural
      analogues.
AB  - Dual action antidepressants have important therapeutic implications. Methylene
      blue (MB), a charged compound structurally related to tricyclic antidepressants,
      acts on both monoamine oxidase (MAO) and the nitric oxide (NO)-cGMP pathway, and
      has demonstrated antidepressant activity in rodents. We investigated the
      antidepressant properties of MB and selected structural analogues and whether
      their actions involve MAO, NO synthase (NOS) and regional brain monoamines. Acute
      imipramine (IMI, 15 mg/kg), saline, MB, acriflavine (ACR), methylene green (MG),
      methylene violet (MV), thionine (THI) and tacrine (TAC) (1-60 mg/kg i.p.) were
      tested for antidepressant activity in the forced swim test (FST), as well as MAO
      A/B inhibitory activity. Active antidepressant compounds were subsequently
      studied at their most effective dose during sub-chronic treatment, followed by
      behavioural sampling in the FST and assay of cortico-limbic monoamines and
      hippocampal nitrate (for NOS activity). Only IMI, MB (15, 30, 60 mg/kg) and MG
      (7.5, 25, 40 mg/kg) reduced immobility in the acute FST. MB, MG and ACR were
      potent inhibitors of especially MAO-A. Following sub-chronic treatment, IMI (15
      mg/kg) increased noradrenergic behaviour in the FST, while MB (15 mg/kg) and MG
      (15 mg/kg) enhanced serotonergic behaviour. MB and MG bolstered cortico-limbic
      serotonin (5HT) levels and to a lesser extent l-norepinephrine (l-NE), but did
      not significantly alter regional dopamine (DA) levels. MB, and to lesser degree
      MG, reduced hippocampal nitrate levels. MB and MG present with structure-specific
      antidepressant-like effects following acute and sub-chronic treatment, possibly
      involving NOS and MAO-A inhibition and cortico-limbic 5HT and l-NE release. A
      role for MAO-B and DA appears minimal.

PMID- 20699088
TI  - Butein downregulates chemokine receptor CXCR4 expression and function through
      suppression of NF-kappaB activation in breast and pancreatic tumor cells.
AB  - The CXC chemokine receptor-4 (CXCR4), a Gi protein-coupled receptor for the
      ligand CXCL12/stromal cell-derived factor-1alpha (SDF-1alpha), is known to be
      expressed in various tumors. This receptor mediates homing of tumor cells to
      specific organs that express the ligand CXCL12 for this receptor and plays an
      important role in tumor growth, invasion, metastasis, and angiogenesis. Thus, a
      priori, agents that can downregulate CXCR4/CXCL12 signaling cascade have
      potential against cancer metastasis. In this study, we report the identification
      of butein (3, 4, 2', 4'-tetrahydroxychalcone) as a novel regulator of CXCR4
      expression and function. We found that butein downregulated the expression of
      CXCR4 in HER2-overexpressing breast cancer cells in a dose- and time-dependent
      manner. The decrease in CXCR4 expression induced by butein was not cell type
      specific as the inhibition also occurred in pancreatic, prostate, multiple
      myeloma, head and neck, and hepatocellular cancer cell lines. When investigated
      for the molecular mechanism(s), it was found that the downregulation of CXCR4 was
      not due to proteolytic degradation but rather to transcriptional regulation as
      indicated by downregulation of mRNA expression, inhibition of NF-kappaB
      activation evident by both DNA binding, and reporter assays, and suppression of
      chromatin immunoprecipitation activity. Suppression of CXCR4 expression by butein
      correlated with the inhibition of CXCL12-induced migration and invasion of both
      breast and pancreatic cancer cells. Overall, our results demonstrate for the
      first time that butein is a novel inhibitor of CXCR4 expression and thus has a
      potential in suppressing metastasis of cancer.

PMID- 20699089
TI  - Adenosine A1 receptors are modified by acute treatment with methylphenidate in
      adult mice.
AB  - In recent years misuse of methylphenidate (MPH) has been reported. The main
      pharmacological target of methylphenidate is the dopaminergic system. Adenosine
      is a neuromodulator that influences the dopaminergic neurotransmission, but
      studies on MPH and adenosine are still lacking. In this study, adult mice were
      acutely treated with MPH (5mg/kg, i.p.) and to model misuse, they received an
      acute overdosage (50mg/kg, i.p). The involvement of adenosine A(1) receptors in
      anxiety-related behavior and locomotor and exploratory activity was examined. The
      administration of methylphenidate (5 and 50mg/kg) 30 min before the exposure to
      open field arena did not modify locomotor activity. The anxiolytic-like behavior
      was observed with both doses of MPH as revealed by the increase on the number of
      entries and the time spent in the open arms in the elevated plus-maze. Pre
      treatment with selective adenosine A(1) receptor antagonist (DPCPX 1mg/kg, i.p.)
      did not prevent anxiolytic effect caused by MPH 50mg/kg. Immunoblotting of
      frontal cortex and hippocampal extracts revealed that MPH 50mg/kg increased 88%
      adenosine A(1) receptor density in the frontal cortex. Extracts from hippocampus
      did not reveal any differences in the adenosine A(1) receptor density. Our
      findings ruled out the participation of adenosine A(1) receptors on the MPH
      triggered anxiolytic effects. However, the density of adenosine A(1) receptors
      increased in a brain area strictly involved in the MPH-mediated effects. Thus,
      the adenosinergic system may play a role in the methylphenidate actions in the
      central nervous system.

PMID- 20699090
TI  - Triglycerides and gallstone formation.
AB  - Changes in bile acid (BA) metabolism and gallbladder function are critical
      factors in the pathogenesis of gallstones. Patients with hypertriglyceridemia
      (HTG) - often overweight and insulin resistant - are at risk for gallstone
      disease. The question arises whether HTG itself contributes to gallstone
      formation or whether gallstone disease only associates with this disorder.
      Triglycerides are formed in response to fluxes of non-esterified fatty acids and
      glucose. Hypertriglyceridemia results from either overproduction of triglycerides
      by the liver, impaired lipolysis or a combination of both. Hyperinsulinemia, as
      observed in the insulin resistant state, stimulates very low-density lipoprotein
      (VLDL)-triglyceride synthesis. Peroxisome proliferator-activated receptors
      (PPARs), liver X receptors (LXRs), farnesoid X receptor (FXR) and hepatocyte
      nuclear factor 4alpha (HNF4alpha) are the nuclear receptors involved in the
      regulation of lipogenesis. Microsomal triglyceride transfer protein (MTP) is
      involved in the production of VLDL and its activation is also under control of
      transcription factors as FXR and Forkhead box-O1 (FoxO1). Triglyceride and BA
      metabolism are linked. There is an inverse relationship between bile acid fluxes
      and pool size and VLDL production and SHP (small heterodimer partner) and FXR are
      the link between BAs and TG metabolism. BAs are also ligands for FXR and G
      protein-coupled receptors, such as TGR5. FXR activation by BAs suppresses the
      expression of MTP, transcription factor sterol regulatory element binding protein
      (SREBP)-1c and other lipogenic genes. LXRs stimulate lipogenesis whereas FXRs
      inhibit the metabolic process. Synthesis of BAs from cholesterol occurs either
      via the classical pathway (7alpha-hydroxylation of cholesterol; CYP7A1) or via
      the alternate pathway (CYP39A1 or CYP7B1). BAs induce FXR, which inhibits CYP7A1
      transcription by activation of SHP and inhibition of HNF4alpha transactivation.
      Bile composition (supersaturation with cholesterol), gallbladder dysmotility,
      inflammation, hypersecretion of mucin gel in the gallbladder and slow large
      intestinal motility and increased intestinal cholesterol absorption may
      contribute to the pathogenesis of cholesterol gallstones. In HTG patients
      supersaturated bile may be related to the presence of obesity rather than to HTG
      itself. Contraction and relaxation of the gallbladder are regulated by neuronal,
      hormonal and paracrine factors. Postprandial gallbladder emptying is regulated by
      cholecystokinin (CCK). Poor postprandial gallbladder contraction may be due to
      the magnitude of the CCK response and to the amount of CCK receptors in the
      gallbladder smooth muscle cells. In the fasting state gallbladder motility is
      associated with the intestinal migrating motor complex (MMC) activity and with
      elevated plasma motilin levels. Fibroblast growth factor (FGF19), produced on
      arrival of bile acids in the ileum, is also important for gallbladder motility.
      Gallbladder motility is impaired in HTG patients compared to BMI matched
      controls. There is evidence that the gallbladder in HTG is less sensitive to CCK
      and that this sensitivity improves after reversal of high serum TG levels by use
      of TG lowering agents. In hypertriglyceridemia TG lowering therapy (fibrates or
      fish-oil) is essential to prevent cardiovascular disease and pancreatitis.
      Fibrates, however, also increase the risk for cholelithiasis by increasing
      biliary cholesterol saturation and by reduction of bile acid synthesis. On the
      other hand fish-oil decreases biliary cholesterol saturation. Fish-oil may
      increase bile acid synthesis by activation of 7alpha-hydroxylase and may inhibit
      VLDL production and secretion through activation of nuclear factors and increased
      apoB degradation. In HTG patients, gallbladder motility improves during
      bezafibrate as well as during fish-oil therapy. The question remains whether
      improvement of gallbladder motility and increased lithogenicity of bile by
      bezafibrate therapy counteract each other or still result in gallstone formation
      in HTG patients.

PMID- 20699091
TI  - Estrogen receptor alpha genetic variants and the risk of stroke in a South Indian
      population from Andhra Pradesh.
AB  - BACKGROUND: Stroke is a complex disease caused by combination of multiple risk
      factors. Recent findings have suggested that stroke has a strong genetic
      component. Evidence suggests that variations in the estrogen receptor alpha
      (ESR1) gene may influence stroke risk. AIMS: The present study was carried out to
      investigate the role of ESR1 gene polymorphisms [PvuII (rs 2234693) and XbaI (rs
      9340799)] with stroke in a South Indian population from Andhra Pradesh. The
      relationship between ESR1 genotypes with estradiol levels was also investigated
      in pre- and postmenopausal women. METHODS: Four hundred patients with ischemic
      stroke and three hundred and eighty subjects were enrolled in this case-control
      study. Ischemic stroke subtypes were classified according to TOAST (Trial of Org
      10172 in Acute Stroke Treatment) classification. The ESR1 PvuII and XbaI
      genotypes were determined by PCR-RFLP method. Serum estradiol was measured by
      ELISA. RESULTS: In case of PvuII polymorphism statistically significant
      difference was observed in the genotypic and allelic frequencies between patients
      and controls (joint analysis of men and women) (p=0.003 and 0.004 respectively).
      However, the XbaI genotypes and alleles did not show an association with stroke
      in the study population. When the analysis was carried out separately for men and
      women, the PvuII polymorphism did not show significant association with stroke in
      men; women showed a significant association. Further when women were grouped in
      to premenopausal and postmenopausal, the premenopausal group did not show a
      significant association with the polymorphism but significant association with
      stroke was found in postmenopausal women. A stepwise multiple logistic regression
      analysis confirmed these findings. Women with pp genotype had low estradiol
      levels in comparison with PP genotypic individuals (p<0.05). Further evaluating
      the association of this polymorphism with stroke subtypes, we found significant
      association of PvuII polymorphism with extracranial atherosclerosis, lacunar and
      cardioembolic stroke. CONCLUSION: In conclusion our results suggest the PvuII
      gene polymorphism is significantly associated with stroke in postmenopausal women
      in a South Indian population from Andhra Pradesh. The pp genotypes have average
      17beta estradiol levels which are significantly low in comparison with PP
      genotypes. Therefore postmenopausal women with a high frequency of pp genotype
      are more predisposed to ischemic stroke. However, this is a preliminary study and
      the results need to be confirmed in a larger cohort.

PMID- 20699092
TI  - Cathepsin B and cystatin C play an inflammatory role in gouty arthritis of the
      knee.
AB  - BACKGROUND: To relate the expression of the matrix degrading proteinase cathepsin
      B and its endogenous inhibitor cystatin C in the synovial fluid (SF) to the
      clinical and laboratory variables of joint inflammation in gouty arthritis of the
      knee. METHODS: Thirty-nine SF samples were obtained from inflamed knees of
      patients with acute gout. The levels of cathepsin B, cystatin C, urokinase-type
      plasminogen activator (uPA), soluble uPA receptor (suPAR) and PA inhibitor type-1
      (PAI-1), activities of matrix metalloproteinase-2 (MMP-2) and MMP-9, and cell
      counts as well as local arthritis activity scores (LAS) were examined. RESULTS:
      The increases of cathepsin B levels correlated with increased leukocyte and
      neutrophil counts, latent MMP-9 (pro-MMP-9) activities, uPA, suPAR and PAI-1
      levels, and uPA/PAI-1 ratios. Increased cystatin C levels corresponded closely
      with increased LAS, leukocyte and neutrophil counts, pro-MMP-9 activities, uPA,
      suPAR and PAI-1 levels, and uPA/PAI-1 ratios. Moreover, there was a correlation
      between cathepsin B and cystatin C levels. CONCLUSIONS: These results show a high
      correlation between the cathepsin B/cystatin C system and markers of joint
      inflammation in acute gout of the knee, demonstrating the pathologic role of
      cathepsin B and cystatin C in inflammation.

PMID- 20699093
TI  - Point of care testing in a large urban academic medical center: evolving test
      menu and clinical applications.
AB  - INTRODUCTION: There have been many reports describing individual POCT
      technologies but there are no recent studies describing the organizational scope
      and impact of a POCT program. METHODS: Our menu of POCT tests has increased to 26
      and the test volume to 664,287 tests/year equivalent to 14.5% of the volume of
      the central core laboratory. POCT is performed in nearly all inpatient units and
      in a variety of outpatient settings. RESULTS: Cumulatively 84.6% of the test
      volume and most testing sites can be accounted for by 4 traditional tests
      (bedside glucose testing, fecal occult blood, dipstick urinalysis and activated
      clotting time). Most POCT tests are not performed because of a true medical
      necessity but rather to improve the efficiency of clinical operations.
      CONCLUSION: We are experiencing a significant increase in requests for new POCT
      tests. Unlike established high volume conventional POC tests, these new requests
      originate from specialized services seeking to improve the efficiency of clinical
      operations.

PMID- 20699094
TI  - Assessment of inflammatory markers in patients with community-acquired pneumonia-
      influence of antimicrobial pre-treatment: results from the German competence
      network CAPNETZ.
AB  - BACKGROUND: There is almost no data about the influence of antimicrobial pre
      treatment (APT) on levels of inflammatory markers in community acquired pneumonia
      (CAP). The aim of this study was to investigate the influence of APT on
      inflammatory markers in CAP. METHODS: 991 hospitalized patients (64.3+/-17.6
      years, 61% male) with CAP were enrolled. In all patients procalcitonin (PCT), C
      reactive protein (CRP), and leukocyte count (WBC) were determined. Patients were
      followed-up for 28 days for survival. RESULTS: 232 patients (23.4%) had APT, 759
      had no APT. Patients without APT had significantly higher levels of PCT and WBC
      but not of CRP compared to those with APT. In patients without APT, survivors
      compared to non-survivors had lower values of PCT (0.20 ng/mL; 0.02-169.10 vs.
      0.83 ng/mL; 0.04-516.30, p<0.0001), WBC (12.4*10(9)/L; 1.3-49.9 vs. 14.9*10(9)/L;
      3.7-34.5, p=0.047) and CRP (107.0mg/mL; 0.3-567.0 vs. 143.5mg/mL; 5.0-589.0,
      p=0.006). However, in patients with APT, the values of PCT, WBC and CRP were not
      significantly different in survivors and non-survivors. Cox regression analysis
      confirmed that PCT, CRP and WBC were predictive for 28 day mortality in patients
      without APT but not in those with APT. CONCLUSIONS: PCT and WBC but not CRP
      levels are higher in patients without APT compared to those with APT. PCT, CRP
      and WBC are predictive for 28 days mortality exclusively in patients without APT.
      Interpretation of inflammatory parameters has to take into account possible APT.

PMID- 20699095
TI  - WITHDRAWN: Aldose reductase is a potent regulator of TGF-beta1-induced expression
      of fibronectin in human mesangial cells.
AB  - This article has been withdrawn at the request of the author(s) and/or 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- 20699096
TI  - Human papillomavirus (HPV) and Merkel cell polyomavirus (MCPyV) in non small cell
      lung cancer.
AB  - Certain types of human papillomavirus (HPV) induce cancers, especially cervical
      cancers in women. A meta-analysis of the literature suggests that HPV is also
      associated with 20%-25% of non small cell lung carcinoma (NSCLC). Merkel cell
      Polyomavirus (MCPyV) causes most Merkel cell carcinomas in immunocompromised
      hosts, and is associated with some squamous carcinomas of skin in immunocompetent
      individuals. Since both oncogenic viruses appear to involve the tonsils and,
      therefore, have clear access to the lungs, we examined that the possible
      association of HPV and MCPyV infections with lung cancers, especially, NSCLC.
      DNAs were extracted from 51 frozen tissues from 30 lung cancer patients, and
      examined for the presence of HPV and MCPyV by PCR and DNA sequencing analysis.
      Clinical data was correlated with the viral status. HPVs were only detected in 5
      adenocarcinomas (16.7% of all lung cancers examined). Three were positive for HPV
      16, 1 for HPV-11 and 1 had an unknown HPV type DNA. None was identified in benign
      tissue. MCPyV DNA was detected in 5 NSCLCs (16.7%). Three of the 5 were
      identified in squamous carcinomas, 1 in adenocarcinoma, and 1 in an unspecified
      NSCLC. Two additional samples were positive for MCPyV DNA within benign adjacent
      lung tissue only. In one adenocarcinoma, HPV-11 was identified in an
      adenocarcinoma, and MCPyV DNA was detected in the adjacent "benign" tissue. HPV
      and MCPyV were directly associated with 33.3% of NSCLC. Further studies are
      necessary to determine if polyomavirus and papillomavirus are necessary risk
      factors for some cases of NSCLC.

PMID- 20699097
TI  - The C/EBPbeta isoform, liver-inhibitory protein (LIP), induces autophagy in
      breast cancer cell lines.
AB  - Autophagy is a process involving the bulk degradation of cellular components in
      the cytoplasm via the lysosomal degradation pathway. Autophagy manifests a
      protective role in stressful conditions such as nutrient or growth factor
      depletion; however, extensive degradation of regulatory molecules or organelles
      essential for survival can lead to the demise of the cell, or autophagy-mediated
      cell death. The role of autophagy in cancer is complex with roles in both tumor
      suppression and tumor promotion proposed. Here we report that an isoform of the
      C/EBPbeta transcription factor, liver-enriched inhibitory protein (LIP), induces
      cell death in human breast cancer cells and stimulates autophagy. Overexpression
      of LIP is incompatible with cell growth and when cell cycle analysis was
      performed, a DNA profile of cells undergoing apoptosis was not observed. Instead,
      LIP expressing cells appeared to have large autophagic vesicles when examined via
      electron microscopy. Autophagy was further assessed in LIP expressing cells by
      monitoring the development of acidic vesicular organelles and conversion of LC3
      from the cytoplasmic form to the membrane-bound form. Our work shows that
      C/EBPbeta isoform, LIP, is another member of the group of transcription factors,
      including E2F1 and p53, which are capable of playing a role in autophagy.

PMID- 20699098
TI  - Reporter gene expression at single-cell level characterized with real-time RT
      PCR, chemiluminescence, fluorescence, and electrochemical imaging.
AB  - mRNA from single cells was quantified using real-time RT-PCR after recording the
      address and reporter protein activity with chemiluminescence, fluorescence, and
      electrochemical techniques, using luciferase, green fluorescent protein, and
      secreted alkaline phosphatase. mRNA copy number ranging from below 10(3) to 10(7)
      in single cells showed a lognormal distribution for both externally introduced
      reporter genes and internally expressed genes. The fluctuation in the gene
      expression decreased with the increase of the number of cells picked but did not
      decrease with the increase of mRNA copy number per cell. We found that the
      correlation coefficients for mRNA and protein expression in logarithmic plot at
      single-cell level were much lower than 1.00.

PMID- 20699099
TI  - A cytotoxic peptide from a marine sponge exhibits ion channel activity through
      vectorial-insertion into the membrane.
AB  - A cytotoxic peptide, polytheonamide B (pTB), from marine sponge was examined for
      cytotoxic spectrum and specific activity to mammalian cells was demonstrated. pTB
      is composed of alternative D- and L-amino acid residues throughout the 48-mer
      peptide. This suggests the formation of a beta-helix similar to gramicidin
      channels. Planar bilayer experiments revealed that pTB forms monovalent cation
      selective channels, being compatible with the inner pore diameter of ~4A for a
      beta-helical structure. pTB penetrated vectorially into the membrane, formed a
      channel by means of a single molecule, and remained in the membrane. These
      functional properties may account for specific cytotoxic activity.

PMID- 20699100
TI  - Factors affecting susceptibility to RNA interference in Haemonchus contortus and
      in vivo silencing of an H11 aminopeptidase gene.
AB  - Gene silencing by RNA interference (RNAi) has been applied very successfully to
      Caenorhabditis elegans to study gene function but has proven less effective in
      parasitic nematodes. In the sheep gastrointestinal nematode Haemonchus contortus,
      previous studies demonstrated reproducible silencing of beta-tubulin but not of
      other genes targeted. Here we aimed to examine whether the level of target
      transcript or site of gene expression influence susceptibility to RNAi by
      soaking. Target genes represented by a high number of expressed sequence tags
      (ESTs) in the H. contortus L3 stage were not reproducibly silenced. In contrast,
      four out of six genes putatively expressed in the intestine, excretory cell or
      amphids were consistently silenced by RNAi. This suggests that genes expressed in
      sites accessible to the environment are more likely to be susceptible to RNAi by
      soaking. Silenced genes included those encoding the highly protective gut
      aminopeptidase H11, secretory protein Hc-ASP-1, beta-tubulin and homologues of
      aquaporin and RNA helicase. To determine whether RNAi silencing of H11 could
      mimic H11 vaccination in reducing worm and egg counts, we examined the in vivo
      effects of H11 RNAi. This is the first, to our knowledge, in vivo study of RNAi
      in an animal parasitic nematode. RNAi of the H11 gene in infective larvae prior
      to infection resulted in a 57% reduction in faecal egg count (FEC), 40% reduction
      in worm burden and 64% decrease in aminopeptidase activity compared with pre
      soaking in control dsRNA. Thus, in this study we have established that RNAi is a
      valid and feasible approach to identify essential gene function. However, using
      current methods, this may be limited to genes expressed in accessible sites.

PMID- 20699101
TI  - Virulence is context-dependent in a vertically transmitted aquatic host
      microparasite system.
AB  - Recent work has suggested that the outcomes of host-symbiont interactions can
      shift between positive, neutral and negative depending on both biotic and abiotic
      conditions. Even organisms traditionally defined as parasites can have positive
      effects on hosts under some conditions. For a given host-parasite system, the
      effects of infection on host fitness can depend on host vigour, route of
      transmission and environmental conditions. We monitored sublethal microsporidian
      infections in populations of Gammarus pseudolimnaeus (Amphipoda: Gammaridae) from
      four cool water streams in southwestern Michigan, USA. Our objectives were to:
      (i) infer the mechanism of transmission (horizontal, vertical or mixed) from
      observed effects of infection on host fitness, (ii) determine if the magnitude of
      the effects on host fitness is a function of parasite load (infection intensity)
      compared with simple presence or absence of infection, and (iii) determine if
      there is variation in parasite effects on host fitness in isolated populations.
      PCR and DNA sequence analyses revealed that there were two microsporidia present
      among the four host populations: Dictyocoela sp. and Microsporidium sp. PCR
      screening of a subset of infected hosts showed that Dictyocoela sp. accounted for
      90% of infections and was present in all four G. pseudolimnaeus populations,
      while Microsporidium sp. was found in two populations but was only relatively
      common in one. We found very low prevalence in males (~5%), but high prevalence
      in females (range: 37-85%). Female fitness was positively associated with
      infection in two streams, resulting from either higher fecundity or more
      reproductive bouts. Infection had a negative effect on the number of reproductive
      bouts in a third population, and no effect on fecundity in a fourth population.
      Infection intensity explained additional variation in fecundity in one
      population; females with intermediate infection intensity had higher fecundity
      than females with either light or heavy infection intensity. Given the high
      prevalence of infection in females compared with males and the generally weak
      negative fitness effects coupled with some positive fitness effects, it is likely
      that both Dictyocoela sp. and Microsporidium sp. are primarily vertically
      transmitted, feminizing microsporidia. Our results suggest that microsporidian
      effects on G. pseudolimnaeus fitness were context-dependent and varied with host
      sex and local environment.

PMID- 20699102
TI  - Leaky vessels as a potential source of stromal acidification in tumours.
AB  - Malignant tumours are characterised by higher rates of acid production and a
      lower extracellular pH than normal tissues. Previous mathematical modelling has
      indicated that the tumour-derived production of acid leads to a gradient of low
      pH in the interior of the tumour extending to a normal pH in the peritumoural
      tissue. This paper uses mathematical modelling to examine the potential of leaky
      vessels as an additional source of stromal acidification in tumours. We explore
      whether and to what extent increasing vascular permeability in vessels can lead
      to the breakdown of the acid gradient from the core of the tumour to the normal
      tissue, and a progressive acidification of the peritumoural stroma. We compare
      our mathematical simulations to experimental results found in vivo with a tumour
      implanted in the mammary fat pad of a mouse in a window chamber construct. We
      find that leaky vasculature can cause a net acidification of the normal tissue
      away from the tumour boundary, though not a progressive acidification over time
      as seen in the experiments. Only through progressively increasing the leakiness
      can the model qualitatively reproduce the experimental results. Furthermore, the
      extent of the acidification predicted by the mathematical model is less than as
      seen in the window chamber, indicating that although vessel leakiness might be
      acting as a source of acid, it is not the only factor contributing to this
      phenomenon. Nevertheless, tumour destruction of vasculature could result in
      enhanced stromal acidification and invasion, hence current therapies aimed at
      buffering tumour pH should also examine the possibility of preventing vessel
      disruption.

PMID- 20699103
TI  - Size and shape after-effects: same or different mechanism?
AB  - The shape-frequency and shape-amplitude after-effects, or SFAE and SAAE, are
      shifts in the perceived shape-frequency and perceived shape-amplitude of a
      sinusoidal test contour following adaptation to a similar-shaped contour. These
      shape-effects are the shape analogs of the well-known size after-effect
      discovered by Blakemore and Sutton (1969), so it is possible that they are
      mediated by a size-sensitive mechanism. We tested this possibility by comparing
      the magnitudes of SFAEs/SAAEs elicited by contour/edge adaptors with those from
      luminance grating and line-grating adaptors. The rationale was that if the shape
      after-effects using the two classes of adaptors were similar, then they would
      likely be mediated by the same mechanism. We found that the SFAE and SAAE were
      greatly reduced when using luminance and line grating adaptors, suggesting that
      the SFAE and SAAE are not mediated primarily by either first- or second-order
      size-sensitive mechanisms. Based on previous studies we conclude that SFAEs/SAAEs
      are mediated by mechanisms primarily sensitive to curvature.

PMID- 20699104
TI  - Expression pattern of a Gram-negative bacteria-binding protein in early embryonic
      development of Artemia sinica and after bacterial challenge.
AB  - Gram-negative bacteria-binding proteins (GNBPs) are important pattern recognition
      receptors (PRRs) in invertebrate innate immune systems. These immune proteins are
      capable of identifying and binding to specific targets on the surface of
      microorganisms, and thereby trigger a variety of defense reactions through the
      activation of protease cascades and intracellular immune signaling pathways. In
      this paper, a full-length cDNA of GNBP coding for a conserved beta-glucan-binding
      domain was isolated from Artemia sinica. Bioinformatic analysis showed that it
      belonged to a new member of the GNBP family. The expression of GNBP was
      investigated at various stages during the embryonic development of A. sinica
      using real-time PCR and immunohistochemistry assay. The result showed that the
      highest expression level was on the 10th day of the embryo. The larvae showed a
      remarkable down-regulation of GNBP transcript after challenged with Gram-negative
      bacteria. In contrast, the level of GNBP transcript in the larvae increased
      gradually after challenged with Gram-positive bacteria. Immunohistochemistry
      assay showed that during embryonic development, GNBP protein was mainly expressed
      in the head, thorax, and on the alimentary canal surface. This new GNBP member
      showed a constitutive and regional expression during the early embryonic
      development of A. sinica, and may therefore play an important role at the adult
      stage, as well as during infection.

PMID- 20699106
TI  - Effect of 'chronic' versus 'acute' ketamine administration and its 'withdrawal'
      effect on behavioural alterations in mice: implications for experimental
      psychosis.
AB  - Lack of appropriate animal models simulating core behavioural aspects of human
      psychosis is a major limitation in schizophrenia research. The use of drugs, that
      is believed to act through N-methyl d-aspartate receptor, has been demonstrated
      to mimic relatively broader range of behavioural symptoms in putative animal
      models. Our goal in this study has been to further evaluate one such drug,
      ketamine in mice and characterize some selective behavioural phenotypes
      associated with the drug dosage, treatment period and withdrawal effects to
      extend the understanding of this model. Our results indicate that acute treatment
      of ketamine (100 mg/kg, i.p.) induced hyperlocomotory response and reduced the
      'transfer-latency time' in passive avoidance test but did not have any effect in
      the forced swim test (negative symptoms). In contrast, chronic administration of
      ketamine not only produced significant 'hyperactivity' response but also enhanced
      the immobility period in animals during the forced swim test and reduced the
      latency period in the passive avoidance test. Further, these behavioural
      alterations persisted at least for 10 days after the withdrawal of ketamine
      treatment. These observations were substantiated by using standard typical and
      atypical antipsychotic drugs, haloperidol (0.25 mg/kg, i.p.), clozapine (10
      mg/kg, i.p.) and risperidone (0.025 mg/kg, i.p.). Therefore, the present study
      suggests that the chronic treatment with ketamine has the potential of exhibiting
      changes in broader range of behavioural domains than the acute treatment. Hence,
      animals chronically treated with ketamine might serve as a useful tool to study
      the underlying pathogenic mechanisms associated with some symptoms in
      schizophrenia and other psychiatric disorders.

PMID- 20699105
TI  - Somatosensory and sensorimotor consequences associated with the heterozygous
      disruption of the autism candidate gene, Gabrb3.
AB  - Autism spectrum disorder (ASD) is diagnosed based on three core features:
      impaired social interactions, deficits in communication and repetitive or
      restricted behavioral patterns. Against this backdrop, abnormal sensory
      processing receives little attention despite its prevalence and the impact it
      exerts on the core diagnostic features. Understanding the source of these sensory
      abnormalities is paramount to developing intervention strategies aimed at
      maximizing the coping ability of those with ASD. Consequently, we chose to
      examine whether sensory abnormalities were present in mice heterozygous for the
      Gabrb3 gene, a gene strongly associated with ASD. Mice were assessed for tactile
      and heat sensitivity, sensorimotor competence (accelerating rotarod task) and
      sensorimotor gating by prepulse inhibition of the acoustic startle reflex (PPI).
      All heterozygotes exhibited an increase in seizure susceptibility and similar
      reductions in Gabrb3 expression in the dorsal root ganglia, spinal cord, whole
      brain and amygdala. Interestingly, significant differences were noted between
      heterozygous variants in regards to tactile sensitivity, heat sensitivity,
      sensorimotor competence and PPI along with differences in Gabrb3 expression in
      the reticular thalamic nucleus and the bed nucleus of stria terminalis. These
      differences were influenced by the heterozygotes' gender and whether the Gabrb3
      gene was of paternal or maternal origin. These results are not adequately
      explained by simple haploinsufficiency of Gabrb3, therefore, additional
      mechanisms are likely to be involved. In addition, this is the first report of
      the occurrence of tactile and heat hypersensitivity in an ASD mouse model, two
      features often associated with ASD.

PMID- 20699107
TI  - Effects of serotonergic drugs on locomotor activity and vigilance states in ring
      doves.
AB  - Serotonergic system is implicated on sleep-waking states in mammals. Since
      studies on serotonin regulation of sleep in birds are scarce, ring dove was
      chosen as experimental subject in the present work. The role of the
      neurotransmitter serotonin on vigilance states was studied in ring doves
      intraperitoneally treated with the 5-HT(1A) agonist 8-OH-DPAT, the 5-HT(1A)
      antagonist WAY100635 and the inhibitor of serotonin synthesis para
      chlorophenylalanine (PCPA) by means of behavioural, electrophysiological and
      infrared actimetry criteria. 8-OH-DPAT (1 mg/kg) treatment increased locomotor
      activity, active waking and grooming states and reduced SWS and REM sleep. Pre
      treatment with WAY100635 (0.5 mg/kg) prevented the effects induced by 8-OH-DPAT.
      Serotonin depletion induced by PCPA treatment (two consecutive injections of 300
      mg/kg over two consecutive days) reduced locomotor activity, waking and grooming
      activity while increased both SWS and REM sleep. Moreover, 8-OH-DPAT (0.5 mg/kg)
      in PCPA treated ring doves produced a notable rise in the locomotor activity,
      active waking and grooming states, while it decreased sleep. Altogether, the
      results support the idea that serotonin plays an active role in wakefulness,
      probably through the activation of 5-HT(1A) receptors that increases wake
      activities and reduces sleep in ring doves.

PMID- 20699108
TI  - Continuous production of ethanol from hexoses and pentoses using immobilized
      mixed cultures of Escherichia coli strains.
AB  - We have developed highly efficient ethanologenic Escherichia coli strains that
      selectively consume pentoses and/or hexoses. Mixed cultures of these strains can
      be used to selectively adjust the sugar utilization kinetics in ethanol
      fermentations. Based on the kinetics of sugar utilization, we have designed and
      implemented an immobilized cell system for the optimized continuous conversion of
      sugars into ethanol. The results confirm that immobilized mixed cultures support
      a simultaneous conversion of hexoses and pentoses into ethanol at high yield and
      at a faster rate than immobilized homogenous cells. Continuous ethanol production
      has been maintained for several weeks at high productivity with near complete
      sugar utilization. The control of sugar utilization using immobilized mixed
      cultures can be adapted to any composition of hexoses and pentoses by adjusting
      the strain distribution of immobilized cells. The approach, therefore, holds
      promise for ethanol fermentation from lignocellulosic hydrolysates where the
      feedstock varies in sugar composition.

PMID- 20699109
TI  - Thymosin alpha 1: biological activities, applications and genetic engineering
      production.
AB  - Thymosin alpha 1 (Talpha1), a 28-amino acid peptide, was first described and
      characterized from calf thymuses in 1977. This peptide can enhance T-cell,
      dendritic cell (DC) and antibody responses, modulate cytokines and chemokines
      production and block steroid-induced apoptosis of thymocytes. Due to its
      pleiotropic biological activities, Talpha1 has gained increasing interest in
      recent years and has been used for the treatment of various diseases in clinic.
      Accordingly, there is an increasing need for the production of this peptide. So
      far, Talpha1 used in clinic is synthesized using solid phase peptide synthesis.
      Here, we summarize the genetic engineering methods to produce Talpha1 using
      prokaryotic or eukaryotic expression systems. The effectiveness of these
      biological products in increasing the secretion of cytokines and in promoting
      lymphocyte proliferation were investigated in vitro studies. This opens the
      possibility for biotechnological production of Talpha1 for the research and
      clinical applications.

PMID- 20699110
TI  - A metabonomic approach for mechanistic exploration of pre-clinical toxicology.
AB  - Metabonomics involves the application of advanced analytical tools to profile the
      diverse metabolic complement of a given biofluid or tissue. Subsequent
      statistical modelling of the complex multivariate spectral profiles enables
      discrimination between phenotypes of interest and identifies panels of
      discriminatory metabolites that represent candidate biomarkers. This review
      article presents an overview of recent developments in the field of metabonomics
      with a focus on application to pre-clinical toxicology studies. Recent research
      investigations carried out as part of the international COMET 2 consortium
      project on the hepatotoxic action of the aminosugar, galactosamine (galN) are
      presented. The application of advanced, high-field NMR spectroscopy is
      demonstrated, together with complementary application of a targeted mass
      spectrometry platform coupled with ultra-performance liquid chromatography. Much
      novel mechanistic information has been gleaned on both the mechanism of galN
      hepatotoxicity in multiple biofluids and tissues, and on the protection afforded
      by co-administration of glycine and uridine. The simultaneous identification of
      both the metabolic fate of galN and its associated endogenous consequences in
      spectral profiles is demonstrated. Furthermore, metabonomic assessment of inter
      animal variability in response to galN presents enhanced mechanistic insight on
      variable response phentoypes and is relevant to understanding wider aspects of
      individual variability in drug response. This exemplar highlights the analytical
      and statistical tools commonly applied in metabonomic studies and notably, the
      approach is applicable to the study of any toxin/drug or intervention of
      interest. The metabonomic approach holds considerable promise and potential to
      significantly advance our understanding of the mechanistic bases for adverse drug
      reactions.

PMID- 20699111
TI  - The complete mitochondrial genome and phylogenomics of a damselfly, Euphaea
      formosa support a basal Odonata within the Pterygota.
AB  - This study determined the first complete mitochondrial genome of a damselfly,
      Euphaea formosa (Insecta: Odonata: Zygoptera), and reconstructed a phylogeny
      based on thirteen protein-coding genes of mitochondrial genomes in twenty-five
      representative hexapods to examine the relationships among the basal Pterygota.
      The damselfly's mitochondrial genome is a circular molecule of 15,700bp long, and
      contains the entire set of thirty-seven genes typically found in insects. The
      gene arrangement, nucleotide composition, and codon usage pattern of the
      mitochondrial genome are similar across the three odonate species, suggesting a
      conserved genome evolution within the Odonata. The presence of the intergenic
      spacer s5 likely represents a synapomorphy for the dragonflies (Anisoptera).
      Maximum parsimony, maximum likelihood, and Bayesian analyses of both nucleotide
      and amino acid sequences cannot support the three existing phylogenetic
      hypotheses of the basal Pterygota (Palaeoptera, Metapterygota, and
      Chiastomyaria). In contrast, the phylogenetic results indicate an alternative
      hypothesis of a strongly supported basal Odonata and a sister relationship of the
      Ephemeroptera and Plecoptera. The unexpected sister Ephemeroptera+Plecoptera
      clade, which contradicts with the widely accepted hypothesis of a monophyletic
      Neoptera, requires further analyses with additional mitochondrial genome sampling
      at the base of the Neoptera.

PMID- 20699112
TI  - Internalisation of hybrid titanium dioxide/para-amino benzoic acid nanoparticles
      in human dendritic cells did not induce toxicity and changes in their functions.
AB  - Nanoparticles (NPs) have been reported to penetrate into human skin through
      lesional skin or follicular structures. Therefore, their ability to interact with
      dendritic cell (DC) was investigated using DCs generated from monocytes (mono
      DCs). Hybrid titanium dioxide/para-amino benzoic acid (TiO(2)/PABA) NPs did not
      induce any cell toxicity. NPs were internalised into DCs through macropinocytosis
      and not by a receptor-mediated mechanism. Confocal microscopy showed that NPs
      were not detected in the nucleus. These data are confirmed by electronic
      microscopy which demonstrated that hybrid NPs were rapidly in contact with
      cellular membrane and localised into cytoplasmic vesicles without colocalisation
      with clathrin-coated vesicles. Hybrid NPs did not induce CD86 or HLA-DR
      overexpression or cytokine secretion (IL-8 and TNF-alpha) indicating no DC
      activation. Internalisation of hybrid NPs did not modify DC response towards
      sensitisers such as nickel and thimerosal or LPS used as positive controls.
      Moreover, hybrid NPs did not induce any oxidative stress implicated in DC
      activation process. After mono-DC irradiation by ultraviolet A (UVA), hybrid NP
      treated cells did not produce UVA-induced reactive oxygen species (ROS) and
      exhibited a better cell viability compared with UVA-irradiated control cells,
      suggesting a protecting effect of hybrid TiO(2)/PABA NPs against UVA-induced ROS.

PMID- 20699113
TI  - A novel dry powder inhaler: Effect of device design on dispersion performance.
AB  - The effect of device geometry and film characteristics on the performance of
      several passive flutter-induced dispersion DPI prototypes was investigated.
      Device resistance measurements indicated that the type of films, type of device
      geometry and specific device dimensions significantly affects the airflow
      resistance of the device. It was found that airflow resistance was positively
      correlated to the turbulence generated within the device. In addition, in vitro
      deposition studies indicated that the device geometry and film properties have a
      significant effect on aerosol dispersion performance. From these studies,
      selected prototypes were observed to have improved aerosolization performance
      without significant increases in device resistance. With further device design
      optimization, flutter induced dispersion DPI may be highly efficient mechanism
      for drug deaggregation and aerosolization.

PMID- 20699114
TI  - Ethanol extracts of Saururus chinensis suppress ovalbumin-sensitization airway
      inflammation.
AB  - AIM OF THE STUDY: The aerial part of Saururus chinensis has been used in folk
      medicine to treat several inflammatory diseases in China and Korea. Previously,
      our group reported that anti-asthmatic activity of an ethanol extract of Saururus
      chinensis (ESC) might occur, in part, via the inhibition of prostaglandin D(2)
      (PGD(2)) and leukotriene C(4) (LTC(4)) production, and degranulation reaction in
      vitro, as well as through the down-regulation of interleukin (IL)-4 and eotaxin
      mRNA expression in an in vivo ovalbumin-sensitization animal model. However, the
      effects of Saururus chinensis on eicosanoid generation, as well as Th2 cytokines
      and eotaxin production in an in vivo asthma model, have not been fully
      investigated. Moreover, it has not been determined whether ESC can ameliorate
      airway inflammation in vivo. In the present study, we investigated the
      therapeutic activity of Saururus chinensis on ovalbumin (OVA)-sensitized airway
      inflammation and its major phytochemical compositions. MATERIALS AND METHODS:
      Asthma was induced in BALB/c mice by ovalbumin-sensitization and inhalation. ESC
      (10-100 mg/kg) or dexamethasone (5 mg/kg), a positive control, was administered 7
      times orally every 12 h from one day before the first challenge to 1 h before the
      second challenge. The recruitment of inflammatory cells and hyperplasia of goblet
      cells were evaluated by H&E and PAS staining. Levels of Th2 cytokines, eotaxin,
      PGD(2) and LTC(4) were measured to evaluate the anti-inflammatory activity of ESC
      in OVA-sensitized mice. Contents of major components were analyzed by HPLC using
      a reversed-phase C18 column. RESULTS: ESC (10 mg/kg) suppressed allergic airway
      inflammation by inhibition of the production of IL-4 (P<0.001), IL-5 (P<0.05), IL
      13 (P<0.001), eotaxin (P<0.001), PGE(2) (P<0.001), LTC(4) (P<0.001) in lung
      extract and IgE level (P<0.001) in the serum. In addition, ESC (50 mg/kg) reduced
      the infiltration of inflammatory cells and hyperplasia of goblet cells in the
      lung tissues. The anti-inflammatory effect of ESC was comparable to that of the
      positive control drug, dexamethasone. Its major phytochemical composition
      includes manassantin A, B and sauchinone. CONCLUSIONS: These results suggest that
      ESC decreased inflammation and mucus secretion in the OVA-induced bronchial
      asthma model, and its anti-asthmatic activity may occur in part via the
      inhibition of Th2 cytokines and eotaxin protein expression, as well as through
      prostaglandin E(2) (PGE(2)) and leukotriene C(4) (LTC(4)) generation. This
      effects may be attributed particularly to the presence of manassantin A, B and
      sauchinone major component evidenced by a HPLC analysis.

PMID- 20699115
TI  - Benefits of napping and an extended duration of recovery sleep on alertness and
      immune cells after acute sleep restriction.
AB  - Understanding the interactions between sleep and the immune system may offer
      insight into why short sleep duration has been linked to negative health
      outcomes. We, therefore, investigated the effects of napping and extended
      recovery sleep after sleep restriction on the immune and inflammatory systems and
      sleepiness. After a baseline night, healthy young men slept for a 2-h night
      followed by either a standard 8-h recovery night (n=12), a 30-min nap (at 1 p.m.)
      in addition to an 8-h recovery night (n=10), or a 10-h extended recovery night
      (n=9). A control group slept 3 consecutive 8-h nights (n=9). Subjects underwent
      continuous electroencephalogram polysomnography and blood was sampled every day
      at 7 a.m. Leukocytes, inflammatory and atherogenesis biomarkers (high-sensitivity
      C-reactive protein, interleukin-8, myeloperoxidase, fibrinogen and
      apolipoproteins ApoB/ApoA), sleep patterns and sleepiness were investigated. All
      parameters remained unchanged in the control group. After sleep restriction,
      leukocyte and - among leukocyte subsets - neutrophil counts were increased, an
      effect that persisted after the 8-h recovery sleep, but, in subjects who had a
      nap or a 10-h recovery sleep, these values returned nearly to baseline.
      Inflammatory and atherogenesis biomarkers were unchanged except for higher
      myeloperoxidase levels after sleep restriction. The increased sleepiness after
      sleep restriction was reversed better in the nap and extended sleep recovery
      conditions. Saliva cortisol decreased immediately after the nap. Our results
      indicate that additional recovery sleep after sleep restriction provided by a
      midday nap prior to recovery sleep or a sleep extended night can improve
      alertness and return leukocyte counts to baseline values.

PMID- 20699116
TI  - Molecular characterization, expression analysis, and role of ALDH3B1 in the
      cellular protection against oxidative stress.
AB  - Aldehyde dehydrogenase (ALDH) enzymes are critical in the detoxification of
      aldehydes. The human genome contains 19 ALDH genes, mutations in which are the
      basis of several diseases. The expression, subcellular localization, enzyme
      kinetics, and role of ALDH3B1 in aldehyde- and oxidant-induced cytotoxicity were
      investigated. ALDH3B1 was purified from Sf9 cells using chromatographic methods,
      and enzyme kinetics were determined spectrophotometrically. ALDH3B1 demonstrated
      high affinity for hexanal (K(m)=62 MUM), octanal (K(m)=8 MUM), 4-hydroxy-2
      nonenal (4HNE; K(m)=52 MUM), and benzaldehyde (K(m)=46 MUM). Low affinity was
      seen toward acetaldehyde (K(m)=23.3 mM), malondialdehyde (K(m)=152 mM), and the
      ester p-nitrophenyl acetate (K(m)=3.6 mM). ALDH3B1 mRNA was abundant in testis,
      lung, kidney, and ovary. ALDH3B1 protein was highly expressed in these tissues
      and the liver. Immunofluorescence microscopy of ALDH3B1-transfected human
      embryonic kidney (HEK293) cells and subcellular fractionation of mouse kidney and
      liver revealed a cytosolic protein localization. ALDH3B1-transfected HEK293 cells
      were significantly protected from the lipid peroxidation-derived aldehydes trans
      2-octenal, 4HNE, and hexanal and the oxidants H(2)O(2) and menadione. In
      addition, ALDH3B1 protein expression was up-regulated by 4HNE in ARPE-19 cells.
      The results detailed in this study support a pathophysiological role for ALDH3B1
      in protecting cells from the damaging effects of oxidative stress.

PMID- 20699117
TI  - Sensitivity of continuous performance test (CPT) at age 14 years to developmental
      methylmercury exposure.
AB  - Hit Reaction Time latencies (HRT) in the Continuous Performance Test (CPT)
      measure the speed of visual information processing. The latencies may involve
      different neuropsychological functions depending on the time from test
      initiation, i.e., first orientation, learning and habituation, then cognitive
      processing and focused attention, and finally sustained attention as the dominant
      demand. Prenatal methylmercury exposure is associated with increased reaction
      time (RT) latencies. We therefore examined the association of methylmercury
      exposure with the average HRT at age 14 years at three different time intervals
      after test initiation. A total of 878 adolescents (87% of birth cohort members)
      completed the CPT. The RT latencies were recorded for 10 min, with visual targets
      presented at 1000 ms intervals. After confounder adjustment, regression
      coefficients showed that CPT-RT outcomes differed in their associations with
      exposure biomarkers of prenatal methylmercury exposure: During the first 2 min,
      the average HRT was weakly associated with methylmercury (beta (SE) for a ten
      fold increase in exposure, (3.41 (2.06)), was strongly for the 3-to-6 min
      interval (6.10 (2.18)), and the strongest during 7-10 min after test initiation
      (7.64 (2.39)). This pattern was unchanged when simple reaction time and finger
      tapping speed were included in the models as covariates. Postnatal methylmercury
      exposures did not affect the outcomes. Thus, these findings suggest that
      sustained attention as a neuropsychological domain is particularly vulnerable to
      developmental methylmercury exposure, indicating probable underlying dysfunction
      of the frontal lobes. When using CPT data as a possible measure of neurotoxicity,
      test results should therefore be analyzed in regard to time from test initiation
      and not as overall average reaction times.

PMID- 20699118
TI  - Chronic exposure to low levels of inorganic arsenic causes alterations in
      locomotor activity and in the expression of dopaminergic and antioxidant systems
      in the albino rat.
AB  - Several studies have associated chronic arsenicism with decreases in IQ and
      sensory and motor alterations in humans. Likewise, studies of rodents exposed to
      inorganic arsenic ((i)As) have found changes in locomotor activity, brain
      neurochemistry, behavioral tasks, oxidative stress, and in sensory and motor
      nerves. In the current study, male Sprague-Dawley rats were exposed to
      environmentally relevant doses of (i)As (0.05, 0.5 mg (i)As/L) and to a high dose
      (50 mg (i)As/L) in drinking water for one year. Hypoactivity and increases in the
      striatal dopamine content were found in the group treated with 50 mg (i)As/L.
      Exposure to 0.5 and 50 mg (i)As/L increased the total brain content of As.
      Furthermore, (i)As exposure produced a dose-dependent up-regulation of mRNA for
      Mn-SOD and Trx-1 and a down-regulation of DAR-D2 mRNA levels in the nucleus
      accumbens. DAR-D1 and Nrf2 mRNA expression were down-regulated in nucleus
      accumbens in the group exposed to 50 mg (i)As/L. Trx-1 mRNA levels were up
      regulated in the cortex in an (i)As dose-dependent manner, while DAR-D1 mRNA
      expression was increased in striatum in the 0.5 mg (i)As/L group. These results
      show that chronic exposure to low levels of arsenic causes subtle but region
      specific changes in the nervous system, especially in antioxidant systems and
      dopaminergic elements. These changes became behaviorally evident only in the
      group exposed to 50 mg (i)As/L.

PMID- 20699119
TI  - Expression and regulation of a novel identified TNFAIP8 family is associated with
      diabetic nephropathy.
AB  - Tumor necrosis factor-alpha-inducible protein 8 (TNFAIP8) family are very
      recently identified proteins which share considerable sequence homology to
      regulate cellular and immune homeostasis. However, it is unknown whether TNFAIP8
      family is expressed in the kidney and contributes to the regulation of renal
      functions. Therefore, the present study was designed to characterize the members
      of TNFAIP8 family in the kidney and to explore their possible roles in the
      development and progression of diabetic nephropathy. By RT-PCR and Western blot
      analyses, we found that all members of TNFAIP8 family were detected in the
      kidney. TNFAIP8 and TIPE2 expression was significantly increased in glomeruli
      from streptozotocin (STZ)-induced diabetic rats, and this upregulation was
      further confirmed in renal biopsies of diabetic patients. In in vitro study,
      TNFAIP8 was upregulated in response to high glucose in mesangial cells rather
      than podocytes. Moreover, a direct correlation was observed between expression of
      TNFAIP8 and mesangial cell proliferation and this regulation was associated with
      NADPH oxidase-mediated signaling pathway. However, we failed to observe the
      upregulation of TIPE2 in both mesangial cells and podocytes in response to high
      glucose. In conclusion, the present study addressed the role of TNFAIP8 family in
      diabetic nephropathy. These findings for the first time demonstrate that TNFAIP8
      is one of critical components of a signal transduction pathway that links
      mesangial cell proliferation to diabetic renal injury.

PMID- 20699121
TI  - Adhesive interactions: The multi-task biochemical toolbox of cancer cells.

PMID- 20699120
TI  - Does gene deletion of AMPA GluA1 phenocopy features of schizoaffective disorder?
AB  - Glutamatergic dysfunction is strongly implicated in schizophrenia and mood
      disorders. GluA1 knockout (KO) mice display schizophrenia- and depression-related
      abnormalities. Here, we asked whether GluA1 KO show mania-related abnormalities.
      KO were tested for behavior in approach/avoid conflict tests, responses to
      repeated forced swim exposure, and locomotor responses under stress and after
      psychostimulant treatment. The effects of rapid dopamine depletion and treatment
      with lithium or a GSK-3beta inhibitor (SB216763) on KO locomotor hyperactivity
      were tested. Results showed that KO exhibited novelty- and stress-induced
      locomotor hyperactivity, reduced forced swim immobility and alterations in
      approach/avoid conflict tests. Psychostimulant treatment and dopamine depletion
      exacerbated KO locomotor hyperactivity. Lithium, but not SB216763, treatment
      normalized KO anxiety-related behavior and partially reversed hyperlocomotor
      behavior, and also reversed elevated prefrontal cortex levels of phospho-MARCKS
      and phospho-neuromodulin. Collectively, these findings demonstrate mania-related
      abnormalities in GluA1 KO and, combined with previous findings, suggest this
      mutant may provide a novel model of features of schizoaffective disorder.

PMID- 20699122
TI  - Analysis of messenger RNA expression by in situ hybridization using RNA probes
      synthesized via in vitro transcription.
AB  - The analysis of the spatial patterning of mRNA expression is critically important
      for assigning functional and physiological significance to a given gene product.
      Given the tens of thousands of mRNAs in the mammalian genome, a full assessment
      of individual gene functions would ideally be overlaid upon knowledge of the
      specific cell types expressing each mRNA. In situ hybridization approaches
      represent a molecular biological/histological method that can reveal cellular
      patterns of mRNA expression. Here, we present detailed procedures for the
      detection of specific mRNAs using radioactive RNA probes in tissue sections
      followed by autoradiographic detection. These methods allow for the specific and
      sensitive detection of spatial patterns of mRNA expression, thereby linking mRNA
      expression with cell type and function. Radioactive detection methods also
      facilitate semi-quantitative analyses of changes in mRNA gene expression.

PMID- 20699123
TI  - Functional magnetic resonance imaging using RASER.
AB  - Although functional imaging of neuronal activity by magnetic resonance imaging
      (fMRI) has become the primary methodology employed in studying the brain,
      significant portions of the brain are inaccessible by this methodology due to its
      sensitivity to macroscopic magnetic field inhomogeneities induced near air-filled
      cavities in the head. In this paper, we demonstrate that this sensitivity is
      eliminated by a novel pulse sequence, RASER (rapid acquisition by sequential
      excitation and refocusing) (Chamberlain et al., 2007), that can generate
      functional maps. This is accomplished because RASER acquired signals are purely
      and perfectly T(2) weighted, without any T(2)*-effects that are inherent in the
      other image acquisition schemes employed to date. T(2)-weighted fMRI sequences
      are also more specific to the site of neuronal activity at ultrahigh magnetic
      fields than T(2)*-variations since they are dominated by signal components
      originating from the tissue in the capillary bed. The RASER based fMRI response
      is quantified; it is shown to have an inherently less noisy time series and to
      provide fMRI in brain regions, such as the orbitofrontal cortex, which are
      challenging to image with conventional techniques.

PMID- 20699124
TI  - Factors underlying prefrontal and insula structural alterations in smokers.
AB  - Based upon previous reports of alterations in white matter integrity and gray
      matter density in smokers, we examined these markers in a large, well-matched
      sample of smokers and non-smokers. We further investigated the effect of heavy
      cigarette exposure by using pack-years and the effects of two relatively stable,
      highly heritable traits in smokers (Fagerstrom Test of Nicotine Dependence
      (FTND), a measure of severity of nicotine dependence and Toronto Alexithymia
      Scale (TAS-20), a stable personality trait related to smoking). Forty-eight
      nicotine-dependent subjects and 48 matched controls were included in the
      analyses, with smokers also subdivided into high/low dependence and high/low pack
      years smokers. White matter integrity (fractional anisotropy (FA)) and gray
      matter density (voxel-based morphometry (VBM)) were measured and compared across
      groups. Gray matter density was lower in left prefrontal cortex (PFC) in high
      pack-years smokers and was inversely related to pack-years. In contrast, left
      insular cortex gray matter density was higher in smokers and associated with TAS
      20 total score and with difficulty-identifying-feelings factor. Further, the most
      highly dependent smokers showed lower prefrontal FA, which was negatively
      correlated with FTND. There was no correlation between pack-years and FTND in our
      smoker population. These data suggest chronic tobacco use is correlated with
      prefrontal gray matter damage , while differences in insula gray matter and PFC
      white matter appear to reflect stable and heritable differences between smokers
      and non-smokers.

PMID- 20699127
TI  - TGF-beta in cancer and bone: implications for treatment of bone metastases.
AB  - Bone metastases are common in patients with advanced breast, prostate and lung
      cancer. Tumor cells co-opt bone cells to drive a feed-forward cycle which
      disrupts normal bone remodeling to result in abnormal bone destruction or
      formation and tumor growth in bone. Transforming growth factor-beta (TGF-beta) is
      a major bone-derived factor, which contributes to this vicious cycle of bone
      metastasis. TGF-beta released from bone matrix during osteoclastic resorption
      stimulates tumor cells to produce osteolytic factors further increasing bone
      resorption adjacent to the tumor cells. TGF-beta also regulates 1) key components
      of the metastatic cascade such as epithelial-mesenchymal transition, tumor cell
      invasion, angiogenesis and immunosuppression as well as 2) normal bone remodeling
      and coupling of bone resorption and formation. Preclinical models demonstrate
      that blockade of TGF-beta signaling is effective to treat and prevent bone
      metastases as well as to increase bone mass.

PMID- 20699126
TI  - An international comparison of current strategies to prevent herpesvirus and
      fungal infections in hematopoietic cell transplant recipients.
AB  - Herpes virus (cytometalovirus [CMV], herpes simplex virus, varicella zoster
      virus) and invasive fungal infections continue to cause significant morbidity and
      mortality in allogeneic hematopoietic cell transplant (HCT) recipients despite
      the availability of effective therapies. In this study, we developed an Internet
      based survey, which was distributed to all hematopoietic cell transplant centers
      participating in the Center for International Blood and Marrow Transplant
      Research (CIBMTR) program, to gather information on strategies utilized for the
      prevention of disease caused by herpes viruses and fungal infections between 1999
      and 2003. The survey response rate was 72%, representing 175 programs from 32
      countries. Generally, reported center strategies were in accord with the Center
      for Disease Control and Prevention guidelines published in 2000, with 81% of
      programs using low-dose acyclovir prophylaxis for herpes simplex virus
      seropositive patients, 99% of programs reporting use of a CMV prevention strategy
      during the first 100 days posttransplant for all patients at risk of CMV disease,
      and 90% of programs using antifungal prophylaxis. Seventy percent of programs
      reported routine use of a CMV prevention strategy in high-risk patients after day
      100. The greatest departure from published guidelines was the use of acyclovir
      prophylaxis for varicella zoster virus seropositive recipients in 75% of
      programs. There were very few reported changes within centers in practices over
      the study time period. Significant regional variations were found with regard to
      surveillance procedures and treatment durations. There were no significant
      differences in treatment practices by center size and very few differences found
      between those centers that reported treating primarily pediatric patients versus
      primarily adult patients. In summary, our survey demonstrates overall agreement
      with published guidelines for the prevention of disease because of herpesviruses
      and fungal infections with significant regional differences found in duration of
      antiviral prophylaxis, duration of preemptive therapy, and duration and dosing of
      antifungal prophylaxis. Center size and age of primary patient population were
      not associated with many reported differences in strategies.

PMID- 20699128
TI  - Genetic loci for bone architecture determined by three-dimensional CT in crosses
      with the diabetic GK rat.
AB  - The F344 rat carries alleles contributing to bone fragility while the GK rat
      spontaneously develops type-2 diabetes. These characteristics make F344*GK
      crosses well suited for the identification of genes related to bone size and
      allow for future investigation on the association with type-2 diabetes. The aim
      of this study was to identify quantitative trait loci (QTLs) for bone size
      phenotypes measured by a new application of three-dimensional computed tomography
      (3DCT) and to investigate the effects of sex- and reciprocal cross. Tibia from
      male and female GK and F344 rats, representing the parental, F1 and F2
      generations, were examined with 3DCT and analyzed for: total and cortical
      volumetric BMD, straight and curved length, peri- and endosteal area at mid
      shaft. F2 progeny (108 male and 98 female) were genotyped with 192 genome-wide
      microsatellite markers (average distance 10 cM). Sex- and reciprocal cross
      separated QTL analyses were performed for the identification of QTLs linked to
      3DCT phenotypes and true interactions were confirmed by likelihood ratio analysis
      in all F2 animals. Several genome-wide significant QTLs were found in the sex-
      and reciprocal cross-separated progeny on chromosomes (chr) 1, 3, 4, 9, 10, 14,
      and 17. Overlapping QTLs for both males and females in the (GK*F344)F2 progeny
      were located on chr 1 (39-67 cM). This region confirms previously reported pQCT
      QTLs and overlaps loci for fasting glucose. Sex separated linkage analysis
      confirmed a male specific QTL on chr 9 (67-82 cM) for endosteal area at the
      fibula site. Analyses separating the F2 population both by sex and reciprocal
      cross identified cross specific QTLs on chr 14 (males) and chr 3 and 4 (females).
      Two loci, chr 4 and 6, are unique to 3DCT and separate from pQCT generated loci.
      The 3DCT method was highly reproducible and provided high precision measurements
      of bone size in the rat enabling identification of new sex- and cross-specific
      loci. The QTLs on chr 1 indicate potential genetic association between bone
      related phenotypes and traits affecting type-2 diabetes. The results illustrate
      the complexity of the genetic architecture of bone size phenotypes and
      demonstrate the importance of complementary methods for bone analysis.

PMID- 20699129
TI  - The effect of bone strontium on BMD is different for different manufacturers' DXA
      Systems.
AB  - Osteoporotic patients treated with strontium ranelate show relatively large
      increases in bone mineral density (BMD) measured by dual-energy X-ray
      absorptiometry (DXA) due to the replacement of some of the calcium atoms in bone
      by strontium. A study published by Pors Nielsen and colleagues reported that
      replacement of 1% of calcium atoms by strontium causes a 10% increase in BMD. We
      refer to the ratio of the percentage increase in BMD to the molar percentage of
      strontium in bone as the strontium ratio. Theoretically it is expected that the
      strontium ratio should vary between different manufacturers' DXA equipment
      depending on the effective photon energy of the device, an effect that arises
      because of the proximity of the X-ray energies produced by lower energy devices
      to the strontium K-edge at 16 keV. In this study we report theoretical estimates
      of the strontium ratio for two axial DXA systems and two peripheral DXA devices
      based on their broad spectrum X-ray emission. The theoretical figures were
      verified in an experimental study in which the strontium ratio for each device
      was measured using phantoms containing mixtures of hydroxyapatite and strontium
      hydrogen-phosphate. The theoretical values of the strontium ratio were 11.0 for
      the Hologic Discovery, 9.9 for the GE-Lunar Prodigy, 9.1 for the Demetech
      Calscan, and 8.5 for the Osteometer Dexacare G4. Experimental results were 11.2
      for the Discovery, 9.9 for the Prodigy, 8.6 for the Calscan and 6.3 for the
      Dexacare G4. The results confirm both theoretically and experimentally that the
      effect of bone strontium on BMD measurements is different for different DXA
      systems. In the future it might be possible to exploit this effect to make a non
      invasive estimate of average bone strontium content in groups of patients
      receiving strontium medication for osteoporosis.

PMID- 20699125
TI  - NCI First International Workshop on the Biology, Prevention, and Treatment of
      Relapse after Allogeneic Hematopoietic Stem Cell Transplantation: Report from the
      Committee on Treatment of Relapse after Allogeneic Hematopoietic Stem Cell
      Transplantation.
AB  - Relapse is a major cause of treatment failure after allogeneic hematopoietic stem
      cell transplantation (alloHSCT). Treatment options for relapse have been
      inadequate, and the majority of patients ultimately die of their disease. There
      is no standard approach to treating relapse after alloHSCT. Withdrawal of immune
      suppression and donor lymphocyte infusions are commonly used for all diseases;
      although these interventions are remarkably effective for relapsed chronic
      myelogenous leukemia, they have limited efficacy in other hematologic
      malignancies. Conventional and novel chemotherapy, monoclonal antibody therapy,
      targeted therapies, and second transplants have been utilized in a variety of
      relapsed diseases, but reports on these therapies are generally anecdotal and
      retrospective. As such, there is an immediate need for well-designed, disease
      specific trials for treatment of relapse after alloHSCT. This report summarizes
      current treatment options under investigation for relapse after alloHSCT in a
      disease-specific manner. In addition, recommendations are provided for specific
      areas of research necessary in the treatment of relapse after alloHSCT.

PMID- 20699131
TI  - Induction of dendritic cell maturation by beta-glucan isolated from Sparassis
      crispa.
AB  - Sparassis crispa is a medicinal mushroom containing high 6-branched 1,3-beta-D
      glucan (sparan) content, which exhibits immune-mediated antitumor activity. In
      the present study, we investigated the stimulating effect of sparan on phenotypic
      and functional maturation of dendritic cells (DCs). Phenotypic maturation was
      confirmed by the elevated expressions of CD40, CD80, CD86, and MHC-I/II
      molecules. Functional activation was proved by increased cytokine production of
      IL-12, IL-1beta, TNF-alpha, and IFN-alpha/beta, enhanced IL-2 production and
      proliferation of allogenic T cells, and decreased endocytosis. The role of toll
      like receptor 4 (TLR4) as a membrane receptor of sparan was proved by the
      impaired maturation of DCs generated from bone marrow cells of tlr4-/- knock-out
      mice and TLR4-mutated C3H/HeJ mice, and by using anti-MD-2/TLR4 neutralizing
      antibody. Sparan increased phosphorylation of ERK, p38, and JNK, and enhanced
      nuclear translocation of NF-kappaB p50/p65 in DCs. These results indicate that
      sparan activates DCs via MAPK and NF-kappaB signaling pathways, which are
      signaling molecules downstream of TLR4.

PMID- 20699132
TI  - Technological advances in mouse development studies. Preface.

PMID- 20699130
TI  - Platform technology to deliver prophylactic molecules orally: an example using
      the Class A select agent Yersinia pestis.
AB  - Consumed for centuries, lactic acid bacteria are excellent candidates for the
      development of safe mucosal delivery vehicles for prophylactic and therapeutic
      molecules. We have recently reported that the immune response to an effective
      OspA-expressing L. plantarum vaccine for Lyme disease is modulated by the lipid
      modification of the antigen. In this study, we investigated if this technology
      can be applied to developing vaccines for other diseases by focusing on the Class
      A select agent, Yersinia pestis. We used a number of biochemistry and immunology
      techniques to determine the localization of the immunogen in our delivery vehicle
      and to evaluate the mucosal as well as the systemic immune response to the
      immunogen. We found that only LcrV cloned downstream of the signal sequence of B.
      burgdorferi OspA ((ss)LcrV), but not wildtype LcrV (LcrV), is localized to the
      desired peptidoglycan layer of the delivery vehicle. In addition, only mice that
      received L. plantarum expressing (ss)LcrV produced significant titers of IgG
      antibody as well as IgA in distant mucosal sites such as lungs and vagina.
      Furthermore, only L. plantarum expressing (ss)LcrV induced significant amounts of
      pro-inflammatory cytokines TNFalpha, IL-12, IFNgamma and IL-6 as well as anti
      inflammatory IL-10 in human peripheral blood mononuclear cells derived dendritic
      cells, suggesting that the mechanism by which LcrV-expressing L. plantarum
      stimulates the immune response involves polarization to Th1 mediated immunity
      with some involvement of Th2. The study reported here proves that this system is
      a platform technology to develop oral vaccines for multiple diseases.

PMID- 20699133
TI  - Lentivirus transgenesis.
AB  - Lentiviral transgenesis is a promising alternative to direct microinjection of
      DNA into pronuclei, which is by and large restricted to certain mouse strains.
      Lentiviruses are complex retroviruses that integrate their genome into the host
      chromosome. Vectors derived from lentiviruses can efficiently transfer transgenes
      in oocytes and early embryos, which is the basis for the use of these vectors in
      transgenesis. Lentivirus transgenesis has been used in many different species,
      including mouse, rat, pig, bovine, monkeys, and even birds. Here we present a
      protocol for generating transgenic animals by lentiviral transduction of early
      embryos as well as for analyzing viral integrants in transgenic animals.

PMID- 20699134
TI  - Germline modification using mouse spermatogonial stem cells.
AB  - Spermatogonial stem cells (SSCs) in the testes are a new target for germline
      modification. With the development of an in vitro culture system and
      spermatogonial transplantation technique, SSCs can now be manipulated and used as
      an alternative to embryonic stem cells for knockout mice production. The genetic
      and epigenetic stability of SSCs provide new possibilities for the application of
      germline mutagenesis in a wide range of animals.

PMID- 20699135
TI  - Embryonic in vivo electroporation in the mouse.
AB  - Electroporation combined with surgery is a quick and highly efficient method to
      transfect nucleic acids into various embryonic tissues in a spatiotemporally
      restricted manner. Forceps-type electrodes facilitate transfection by delivering
      electric pulses from outside of the embryo. Many electroporated embryos survive
      in the pregnant mouse, are born, and are reared. The developing central nervous
      system (CNS) is a good target for transfection, because there are many neural
      progenitors adjacent to the ventricle, into which nucleic acids are relatively
      easily injected. The expression of transfected genes persists in neurons for
      months.

PMID- 20699136
TI  - Current applications of transposons in mouse genetics.
AB  - Transposable elements (TEs) have been used to study the genetics of a wide
      variety of species, including prokaryotes, plants, yeast, and Drosophila. The use
      of TEs to study mouse genetics has previously not been possible as mice do not
      have endogenous, highly active TEs like other organisms. Over the past decade,
      however, two retrotransposons (class I TEs) and four DNA transposons (class II
      TEs) have been developed that are active when in mice. These elements have been
      used for a variety of applications including germline mutagenesis, transgenesis,
      gene therapy, the production of induced pluripotent stem cells, and cancer
      genetics. The molecular characteristics are summarized for each TE currently used
      in the mouse. In addition, the current applications of these TEs are discussed.

PMID- 20699137
TI  - Functional genomics in the mouse using the sleeping beauty transposon system.
AB  - The resurrection of the Sleeping Beauty (SB) transposon from molecularly extinct
      salmonid transposons at the end of last century opened the door for mouse
      geneticists to develop various transposon-based genetic tool kits, which had
      already been proven instrumental in Drosophila and other invertebrate model
      organisms. Since then, transposon technologies have been successfully applied to
      many aspects of functional genomics, in combination with various well-established
      tools of mouse genetics including transgenesis and gene targeting. In the SB
      system, a substantial fraction of the transposition events occurs on the same
      chromosome, predominantly within 3-4 megabases, while the remainder occurs
      between different chromosomes in a genome-wide manner. By taking advantage of the
      two types of transposition, we have developed applications of the SB system for
      genome-wide mutagenesis as well as region-specific functional analysis of the
      mouse genome.

PMID- 20699138
TI  - The use of DNA transposons for cancer gene discovery in mice.
AB  - Insertional mutagenesis in mice is a potent instrument for cancer gene discovery.
      Until recently, retroviruses were the main experimental tools in this field and
      application of insertional mutagenesis was limited to tissues for which these
      agents have tropism, namely hemopoietic cells and mammary epithelium. However,
      the field has been revolutionized and greatly expanded with the recent
      reanimation of the transposons, a highly flexible group of insertional mutagens
      first discovered in maize, which have now been adapted for use in mammalian
      cells. Transposons do not only extend the application of insertional mutagenesis
      to any tissue of choice, but also allow a more extensive and unbiased coverage of
      the genome, can be designed to selectively activate or inactivate genes, and are
      highly amenable to temporal and spatial control. This chapter gives an overview
      of the design and application of transposons to cancer gene discovery in mice.

PMID- 20699139
TI  - A practical summary of site-specific recombination, conditional mutagenesis, and
      tamoxifen induction of CreERT2.
AB  - The site-specific recombinases, Cre and Flp, are essential tools for altering the
      mouse genome. Since the pioneering work with these enzymes, much progress has
      been made regarding their strengths and weaknesses, as well as how they should be
      applied. Cre recombinase is vital for conditional mutagenesis, including for
      temporal mutagenesis via tamoxifen induction of recombinase-estrogen receptor
      fusion proteins. Recently a Cre-like recombinase, Dre has been added to the
      toolbox. Here, we summarize current knowledge about applications of Cre, Flp, and
      Dre in the mouse and present a protocol for tamoxifen induction of conditional
      mutagenesis.

PMID- 20699140
TI  - A recombineering pipeline to make conditional targeting constructs.
AB  - Here we describe an optimized recombineering protocol for the creation of
      conditional alleles. Recombineering is a DNA engineering methodology based on
      homologous recombination in Escherichia coli. It presents a number of advantages
      over conventional engineering methods, including the ability to place target
      sites for site-specific recombinases at exactly chosen positions. Consequently,
      complicated designs, such as conditional alleles, can be rapidly achieved. We
      have applied these advantages to establish a pipeline method for the fluent
      generation of conditional alleles which employs Cre, Flp, and Dre recombinase
      target sites.

PMID- 20699141
TI  - Confirmation of recombination site functionality in gene targeting vectors using
      recombinase-expressing bacteria.
AB  - Recognition sequences for the site-specific DNA recombinases Cre and FLP are
      commonly incorporated into gene targeting vectors for the purposes of removing
      selection markers or generating conditional alleles. Gene targeting vectors
      typically contain a positive selection marker, such as the neomycin resistance
      gene, flanked by loxP sites. Thus, the selection marker can be removed by
      breeding to a mouse strain which expresses Cre recombinase in its germ line.
      Conditional knockout vectors typically have one or more exons flanked by loxP
      sites and the positive selection marker flanked by FRT sites. Thus, the selection
      marker is removed with FLP recombinase and the knockout allele is generated in
      tissues expressing Cre recombinase. Because the generation of mice by gene
      targeting in embryonic stem (ES) cells is an expensive and time-consuming
      process, it is important to confirm that the recombination sites in your
      targeting vector are functional prior to electroporation of ES cells. This
      chapter describes a simple method for testing the functionality of loxP and FRT
      sites in vivo using Cre- or FLP-expressing bacteria.

PMID- 20699143
TI  - Mapping cell fate and function using recombinase-based intersectional strategies.
AB  - Cell types are typically defined by expression of a unique combination of genes,
      rather than a single gene. Intersectional methods therefore become crucial to
      selectively access these cells for higher resolution fate mapping and functional
      manipulations. Here, we discuss one such intersectional method. Two recombinase
      systems (Cre/loxP and Flp/FRT) work together to remove a double STOP cassette and
      thereby activate expression of a target transgene solely in cells defined by a
      particular pairwise combination of driver genes. Depending on the nature of the
      target transgene, this strategy can be used to deliver cell-lineage tracers,
      sensors, and/or effector molecules to highly selective cell types in vivo. In
      this chapter, we discuss concepts, reagents, and methods underlying this
      intersectional approach and encourage consideration of various intersectional and
      binary methods for accessing uniquely defined cell subsets in the mouse.

PMID- 20699144
TI  - Genome-wide forward genetic screens in mouse ES cells.
AB  - Mouse embryonic stem (ES) cells are an attractive model system for investigating
      mammalian biology. Their relatively stable genome and high amenability to genome
      modification enables the generation of large-scale mutant libraries, which can be
      subsequently used for phenotype-driven genetic screens. While retroviral vectors
      have traditionally been used to generate insertional mutations in ES cells, their
      severe distribution-bias in the mammalian genome substantially limits genome-wide
      mutagenesis. The recent development of the DNA transposon piggyBac offers an
      efficient and highly versatile alternative for achieving more unbiased
      mutagenesis. Furthermore, heterozygous mutations created by insertional mutagens
      can be converted in parallel to homozygosity by using Blm-deficient ES cells,
      allowing genome-wide loss-of-function screens to be conducted. In this chapter,
      we describe the principles underpinning genetic screens in mouse ES cells with
      examples of previously successful screens. Protocols are provided for piggyBac
      transposon-mediated mutagenesis, production of the corresponding homozygous
      mutants in a Blm-deficient genetic background, and methods for mapping and
      validation of mutations recovered from screens of such libraries.

PMID- 20699142
TI  - Genetic fate mapping using site-specific recombinases.
AB  - Understanding how cells are assembled in three dimensions to generate an organ,
      or a whole organism, is a pivotal question in developmental biology. Similarly,
      it is critical to understand how adult stem cells integrate into an existing
      organ during regeneration or in response to injury. Key to discovering the
      answers to these questions is being able to study the various behaviors of
      distinct cell types during development or regeneration. Fate mapping techniques
      are fundamental to studying cell behaviors such as proliferation, movement, and
      lineage segregation, as the techniques allow precursor cells to be marked and
      their descendants followed and characterized over time. The generation of
      transgenic mice, combined with the use of site-specific recombinases (SSR) in the
      mouse genome, has provided a means to develop powerful genetic fate mapping
      approaches. A key advantage of genetic fate mapping is that it allows cells to be
      genetically marked, and therefore the mark is transmitted to all the descendants
      of the initially marked cells. By making modifications to the SSRs that render
      their enzymatic activity inducible, and the development of an assortment of
      reporter alleles for marking cells, increasingly sophisticated genetic fate
      mapping studies can be performed. In this chapter, we review the four main
      genetic fate mapping methods that utilize intrachromosomal recombination to mark
      cells (cumulative, inducible, clonal, and intersectional) and one
      interchromosomal method, the tools required to carry out each approach, and the
      practical considerations that have to be taken into account before embarking on
      each type of genetic fate mapping study.

PMID- 20699145
TI  - Gene trap mutagenesis in the mouse.
AB  - Gene trapping in mouse embryonic stem (ES) cells is an efficient method for the
      mutagenesis of the mammalian genome. Insertion of a gene trap vector disrupts
      gene function, reports gene expression, and provides a convenient tag for the
      identification of the insertion site. The trap vector can be delivered to ES
      cells by electroporation of a plasmid, by retroviral infection, or by transposon
      mediated insertion. Recent developments in trapping technology involve the
      utilization of site-specific recombination sites, which allow the induced
      modification of trap alleles in vitro and in vivo. Gene trapping strategies have
      also been successfully developed to screen for genes that are acting in specific
      biological pathways. In this chapter, we review different applications of gene
      trapping, and we provide detailed experimental protocols for gene trapping in ES
      cells by retroviral and transposon gene trap vectors.

PMID- 20699146
TI  - A wider context for gene trap mutagenesis.
AB  - Gene trapping is a technology originally developed for the simultaneous
      identification and mutation of genes by random integration in embryonic stem (ES)
      cells. While gene trapping was developed before efficient and high-throughput
      gene targeting, a significant proportion of the publically available mutant ES
      cell lines and mice were generated through a number of large-scale gene trapping
      initiatives. Moreover, elements of gene trap vectors continue to be incorporated
      into gene targeting vectors as a means to increase the efficiency of homologous
      recombination. Here, we review the current state of gene trapping technology and
      the applications of specific types of gene trap vector. As a component of this
      analysis, we consider the behavior of specific vector types both from the
      perspective of their application and how they can inform our annotation of the
      mammalian transcriptome. We consider the utility of gene trap vectors as tools
      for cell-based expression analysis, targeted screening in embryonic
      differentiation, and for use in cell lines derived from different lineages.

PMID- 20699147
TI  - Mouse mutagenesis with the chemical supermutagen ENU.
AB  - The generation and analysis of germline mutations in the mouse is one of the
      cornerstones of modern biological research. The chemical supermutagen N-ethyl-N
      nitrosourea (ENU) is the most potent known mouse mutagen and can be used to
      generate point mutations throughout the mouse genome. The progeny of ENU
      mutagenized males can be screened for autosomal dominant phenotypes, or they can
      be used to generate multigeneration pedigrees to screen for autosomal recessive
      traits. The introduction of balancer chromosomes into the breeding scheme can
      allow for the selective capture of mutations in a specific chromosomal region.
      More recent work has demonstrated that the use of animals that already have a
      mutation of interest can lead to the successful isolation of additional mutations
      that modify the original mutant phenotype. Further, modern molecular techniques
      ensure that mutations can be readily identified. We describe here the procedures
      for mutagenizing male mice with ENU and explain the various types of screens that
      can be performed for different kinds of induced mutations. The currently
      published research on ENU mutagenesis in the mouse has only scratched the surface
      of what is possible with this powerful technique, and further work is certain to
      deepen our knowledge of the role of the individual components of the mouse genome
      and the myriad relationships between them.

PMID- 20699148
TI  - Phenotype-driven mouse ENU mutagenesis screens.
AB  - In the past decade, forward genetic screens in the mouse have come into their own
      as a practical method for exploring the genetic basis of many biological
      processes. By looking directly for disruption in a process of interest, genetic
      screens have always been powerful, but completion of the genome sequence has made
      mouse forward genetic screens practical, as well. The sequenced genome means we
      can map and sequence more efficiently than before, so small focused screens are
      now within the reach of even small labs. N-Ethyl-N-nitrosourea (ENU) is the
      preferred mutagen in forward genetic screens, because it is extremely potent in
      the premeiotic male germ line, where it induces point mutations. This last point
      is crucial, as point mutations lead to all classes of mutations (e.g., null,
      hypomorphs, neomorphs, antimorphs, and hypermorphs), which is why forward genetic
      screens can implicate a gene in a particular process when a targeted deletion may
      not. Point mutations often mimic human disease states, yielding highly relevant
      animal models. Since mammals reproduce, lactate, behave, develop, and protect
      themselves from infection differently from other vertebrates, mammalian forward
      genetic screens are uniquely informative. In fact, in the past decade, forward
      genetics has uncovered mutations demonstrating that certain genes exist only in
      mammals, that specific mechanisms function only in mammals, and that particular
      biological processes may exist only in mammals; hence screens focused on these
      processes have identified unsuspected genes. As powerful as the approach is,
      forward genetics remains a method for the committed; the process of screening
      requires organization and tenacity. This chapter is intended to help those who
      are ready to make the commitment by providing practical advice. To this end I
      detail the issues surrounding screen design and screen execution, as well as
      mutation identification and confirmation.

PMID- 20699149
TI  - Using ENU mutagenesis for phenotype-driven analysis of the mouse.
AB  - The use of mutagenesis in invertebrates to generate phenotypic variants has a
      long and productive history. Despite the conclusive demonstration by Russell and
      colleagues in the 1970s that the chemical N-ethyl-N-nitrosourea (ENU) is a highly
      effective mutagen in mice, the application of phenotypic-driven mutagenesis as a
      method to study mammalian biology proceeded slowly. With the development of tools
      for genomic analysis, the task of positional cloning ENU-induced mutations has
      become quite feasible, and this approach has recently been widely applied and
      highly productive. It has specifically lived up to its theoretical utility as
      means to provide insight into the biological roles of genes that is not biased by
      presumptions of their function. While the power of this approach is indisputable,
      the effort necessary for its success remains substantial, requiring careful
      attention to aspects including ENU treatment, mouse husbandry, screen assay
      design, genetic mapping, positional cloning, and mutation validation. In this
      chapter we discuss practical aspects of implementing a phenotype-driven analysis
      of an ENU-mutagenized mouse population.

PMID- 20699150
TI  - Exploration of self-renewal and pluripotency in ES cells using RNAi.
AB  - Embryonic stem cells (ESCs) have the ability to expand indefinitely in vitro and
      give rise to cells of all three germ layers as well as germ cells. For these
      reasons, ESCs hold great promise for biomedicine. In order to harness the
      potential of pluripotent cells, it is necessary to first understand the molecular
      mechanisms that control the pluripotent state. The discovery of RNA interference
      has made such functional analysis, even at high(er) throughput, possible. Here,
      we describe the methods used for high-throughput siRNA screening by high-content
      microscopy to identify gene products that regulate mouse ESC fate decision. In
      addition, we will describe the application of lentivirus-based shRNA knockdown to
      explore or validate the role of candidate genes in ESC pluripotency.

PMID- 20699151
TI  - Transgenic RNAi applications in the mouse.
AB  - Within the past 10 years, RNA interference has emerged as a powerful experimental
      tool as it allows rapid gene function analysis. Unique features such as
      reversibility of gene silencing and simultaneous targeting of several genes
      characterize the approach. In this chapter, transgenic RNAi techniques in reverse
      mouse genetics are discussed and protocols are provided.

PMID- 20699152
TI  - Gene knockdown in the mouse through RNAi.
AB  - RNA interference (RNAi)-mediated gene knockdown has developed into a routine
      method to assess gene function in cultured mammalian cells in a fast and easy
      manner. For the use of RNAi in mice, short hairpin (sh) RNAs expressed from
      transgenic vectors are a fast alternative to conventional knockout approaches. We
      describe our strategy to elicit body-wide, cell type-specific, or inducible gene
      silencing in mice by control of shRNA expression through Cre recombinase or
      doxycycline. For reproducible expression of shRNAs, vectors are placed into the
      Rosa26 locus of ES cells by recombinase-mediated cassette exchange and
      transmitted through the germ line of chimeric mice. The site specific insertion
      of single copy shRNA vectors allows to expedite and reproducible production of
      knockdown mice and provides a simple approach to assess gene function in vivo.

PMID- 20699153
TI  - In vivo analysis of gene knockdown in tetracycline-inducible shRNA mice.
AB  - Expression of small hairpin RNA (shRNA) in mammalian cells can trigger potent
      RNAi-mediated gene silencing. The dominant-acting RNAi can often result in
      phenotypes similar to that of a null allele. Moreover, the generation of shRNA
      knockdown mice and subsequent phenotypic analysis can be achieved in a condensed
      timeline compared to that of conventional gene-targeting knockout strategies.
      Here, we discuss methods for the in vivo analysis of gene function in adult mouse
      tissues following tetracycline-induced RNA knockdown in a single-copy inducible
      polymerase III promoter-driven shRNA system.

PMID- 20699154
TI  - The power of reversibility regulating gene activities via tetracycline-controlled
      transcription.
AB  - Tetracycline-controlled transcriptional activation systems are widely used to
      control gene expression in transgenic animals in a truly conditional manner. By
      this we refer to the capability of these expression systems to control gene
      activities not only in a tissue specific and temporal defined but also reversible
      manner. This versatility has made the Tet regulatory systems to a preeminent tool
      in reverse mouse genetics. The development of the technology in the past 15 years
      will be reviewed and guidelines will be given for its implementation in creating
      transgenic rodents. Finally, we highlight some recent exciting applications of
      the Tet technology as well as its foreseeable combination with other emerging
      technologies in mouse transgenesis.

PMID- 20699155
TI  - Gene expression profiling of mouse oocytes and preimplantation embryos.
AB  - Gene expression profiling using microarray technology is a robust, efficient, and
      cost-effective approach to assay a cell or tissue's transcriptome at a particular
      time or under a specific condition. Application of this technology to oocytes and
      preimplantation embryos has been limited largely because this biological material
      is difficult to acquire in sufficient quantities. We describe here a protocol to
      isolate and amplify mRNA from oocytes and preimplantation embryos that is
      suitable for microarray experiments. This protocol is based on a linear two-step
      amplification protocol using T7 RNA polymerase-based in vitro transcription and
      has been used to isolate more than 80 microg of cRNA from only 20 oocytes or
      preimplantation embryos. Gene expression profiling has provided insight into the
      molecular mechanisms of meiotic maturation, fertilization, and preimplantation
      embryo development. It has also been used to characterize female gametes and
      embryos from animals harboring gene-specific knockouts or knockdowns. Finally,
      this technology has been useful in evaluating how various Assisted Reproductive
      Technologies impact global patterns of gene expression in resulting embryos.

PMID- 20699156
TI  - Interrogating the transcriptome of oocytes and preimplantation embryos.
AB  - During its growth phase, a mouse oocyte accumulates RNA that is the sole template
      for new protein synthesis in the transcriptionally silent interval between growth
      completion and transcriptional activation of the embryonic genome. Over this
      transcriptionally silent interval, almost half the quantity of RNA accumulated in
      the full-grown oocyte is degraded, while stable messages undergo major transcript
      specific polyadenylation fluctuations associated with timely translation of new
      proteins. These processes, in the background of substantial RNA degradation,
      create unique pitfalls for transcriptome analysis. Three particular challenges
      are discussed herein. (1) Systematic errors of relative quantification occur if
      standard approaches are used, wherein samples are normalized to a constant
      quantity of RNA, or when computational analyses are normalized to an apparent
      "constant" endogenous to the sample. We show that use of a fixed quantity of
      exogenous RNA per oocyte or embryo alleviates this problem. (2) Comparison of
      large-scale expression analyses from widely disparate platforms highlights how
      the differing protocols produce correspondingly different lists of genes with
      significant changes in transcript abundance. Only with careful attention to the
      differences among experiments can such discrepancies be understood. (3) The
      complete assessment of changes in expression requires correspondingly
      comprehensive assessment of the role of isoform-specific changes.

PMID- 20699157
TI  - Gene expression profiling of mouse embryos with microarrays.
AB  - Global expression profiling by DNA microarrays provides a snapshot of cell and
      tissue status and becomes an essential tool in biological and medical sciences.
      Typical questions that can be addressed by microarray analysis in developmental
      biology include: (1) to find a set of genes expressed in a specific cell type;
      (2) to identify genes expressed commonly in multiple cell types; (3) to follow
      the time-course changes of gene expression patterns; (4) to demonstrate cell's
      identity by showing similarities or differences among two or multiple cell types;
      (5) to find regulatory pathways and/or networks affected by gene manipulations,
      such as overexpression or repression of gene expression; (6) to find downstream
      target genes of transcription factors; (7) to find downstream target genes of
      cell signaling; (8) to examine the effects of environmental manipulation of cells
      on gene expression patterns; and (9) to find the effects of genetic manipulation
      in embryos and adults. Here, we describe strategies for executing these
      experiments and monitoring changes of cell state with gene expression microarrays
      in application to mouse embryology. Both statistical assessment and
      interpretation of data are discussed. We also present a protocol for performing
      microarray analysis on a small amount of embryonic materials.

PMID- 20699158
TI  - Osteoarthritis. Preface.

PMID- 20699159
TI  - Epidemiology of osteoarthritis.
AB  - Osteoarthritis (OA) is the most common joint disorder in the United States.
      Symptomatic knee OA occurs in 10% men and 13% in women aged 60 years or older.
      The number of people affected with symptomatic OA is likely to increase due to
      the aging of the population and the obesity epidemic. OA has a multifactorial
      etiology, and can be considered the product of an interplay between systemic and
      local factors. Old age, female gender, overweight and obesity, knee injury,
      repetitive use of joints, bone density, muscle weakness, and joint laxity all
      play roles in the development of joint OA, particularly in the weight-bearing
      joints. Modifying these factors may reduce the risk of OA and prevent subsequent
      pain and disability.

PMID- 20699160
TI  - Age-related changes in the musculoskeletal system and the development of
      osteoarthritis.
AB  - Osteoarthritis (OA) is the most common cause of chronic disability in older
      adults. Although classically considered a "wear and tear" degenerative condition
      of articular joints, recent studies have demonstrated an inflammatory component
      to OA that includes increased activity of several cytokines and chemokines in
      joint tissues that drive production of matrix-degrading enzymes. Rather than
      directly causing OA, aging changes in the musculoskeletal system contribute to
      the development of OA by making the joint more susceptible to the effects of
      other OA risk factors that include abnormal biomechanics, joint injury, genetics,
      and obesity. Age-related sarcopenia and increased bone turnover may also
      contribute to the development of OA. Understanding the basic mechanisms by which
      aging affects joint tissues should provide new targets for slowing or preventing
      the development of OA.

PMID- 20699162
TI  - Quality of osteoarthritis care for community-dwelling older adults.
AB  - Evidence-based guidelines have the potential to improve the quality of health
      care by promoting interventions of proven benefit and discouraging unnecessary,
      ineffective, or harmful interventions. Recent years have seen the development of
      several evidence-based guidelines developed for osteoarthritis (OA) management.
      There is some consistency in the numerous guidelines that are available for OA
      management, yet despite some dissemination attempts, clinical practice does not
      reflect these recommendations. Current clinical practice reflects a multitude of
      factors, including clinician and patient preference and health care system
      support. Similarly, guidelines are frequently prescribed independent of context
      and thus implementation can be challenging. Future efforts to guide management of
      OA of the hip or knee are better directed towards implementing practices known to
      be effective in a context-dependent manner to optimize health care quality.

PMID- 20699163
TI  - Contextualizing osteoarthritis care and the reasons for the gap between evidence
      and practice.
AB  - Osteoarthritis (OA) is not an easy condition to manage. It is very heterogeneous,
      has an unpredictable natural history, and has variable effects on health status.
      A wide range of management options is available to OA patients and their health
      care advisors. Guidelines help the clinician through this complexity. There are
      many similarities in the advice offered by different guidelines, suggesting a
      good deal of consensus on what should and should not be offered to patients with
      OA. Several authoritative international guidelines on OA management have appeared
      in recent years. In this article the authors evaluate the United Kingdom National
      Institute for Clinical Excellence guidelines as a contemporary tool to assess the
      context within which care is delivered and as the basis for discussion on the gap
      between evidence and practice.

PMID- 20699161
TI  - The contribution of osteoarthritis to functional limitations and disability.
AB  - This article uses the Disablement Model conceptual framework to guide an analysis
      of the importance of osteoarthritis (OA) in the development of disability. The
      Disablement Model describes the development and progression of disablement from
      impairments to specific functional limitations and disability, and the
      hypothesized role of predisposing risk factors, extra-individual factors, and
      intra-individual factors. A wide range of population and clinical studies have
      characterized the unequivocal contribution of arthritis to the development of
      functional limitations and disability. Evidence overwhelmingly supports a
      significant, moderate independent contribution of arthritis to the onset and
      progression of functional limitations and disability. With respect to important
      risk factors for the development of functional limitations and disability among
      those with OA, the evidence provides strong support for the role of physical
      impairments along with other predisposing and intra-individual factors such as
      age, body mass index, obesity, lack of exercise, comorbid conditions, depression,
      and depressive symptoms. Extra-individual factors included need for aids and
      assistance, and lack of access to public or private transportation. Future
      disablement research must clarify the causal mechanisms behind a potential risk
      factor's impact on disability and delineate the interplay between and among the
      various hypothesized steps in the disablement process.

PMID- 20699164
TI  - Transforming osteoarthritis care in an era of health care reform.
AB  - This article describes the dysfunctional delivery of existing conservative care
      practices in the treatment of osteoarthritis (OA) within the context of a dynamic
      environment of health reform. It is written from the patient perspective of one
      of the authors who is afflicted with OA and with the added clinical view of a
      rheumatologist. The authors envision benefits of more cost-effective care, a
      decrease in the impact of chronic illness on the financial viability of the
      United States, and an improvement in the quality of care provided to patients.
      These benefits can be achieved with tested innovations organized within the
      integrated delivery system described in this article.

PMID- 20699165
TI  - Strength training in older adults: the benefits for osteoarthritis.
AB  - This review summarizes the findings of randomized controlled trials of
      progressive resistance training (PRT) by older people with osteoarthritis (OA). A
      significant benefit was found in lower-extremity extensor strength, function, and
      pain reduction. Across all 3 outcomes, the estimated effect size was moderate,
      which contrasted with trials of PRT in non-OA-specific groups of older adults
      where a large effect was found in strength but a small effect on function. This
      suggests that strength training has strong functional benefits for older adults
      with OA. Older adults with OA benefit from a strength-training program that
      provides progressive overload to maintain intensity throughout an exercise
      program.

PMID- 20699167
TI  - Device use: walking AIDS, braces, and orthoses for symptomatic knee
      osteoarthritis.
AB  - With too few conservative options in the current medical system, increasing
      numbers of osteoarthritis (OA) sufferers are using untested folk remedies and
      self-prescribed dietary supplements. There is enormous popular demand for
      noninvasive and nonpharmacologic therapies for OA, and there is a pressing need
      for clinicians to respond to this demand by updating their practice. This review
      introduces clinicians to the most important noninvasive devices used in the
      conservative management of knee OA. Because the shared goal of these devices is
      to favorably alter lower limb biomechanics, each section of the review considers
      evidence of biomechanical and clinical efficacy.

PMID- 20699168
TI  - Pharmacologic intervention for osteoarthritis in older adults.
AB  - The management of osteoarthritis requires a careful combination of pharmacologic
      and nonpharmacologic therapies to effect improvements in pain and function. When
      choosing pharmacologic therapy, the potential toxicities must be considered
      relative to potential benefits. This review highlights commonly used medications
      and presents the evidence for their effectiveness as well as their toxicities.
      Acetaminophen and nonsteroidal antiinflammatory drugs are the mainstay of
      pharmacologic therapy, but there are numerous adjunctive or alternative
      medications that may provide some benefit to patients with osteoarthritis.

PMID- 20699169
TI  - Total joint replacement in the elderly patient.
AB  - Osteoarthritis of the hip and knee is extremely common in the growing elderly
      population. Total joint replacement (TJR) of the hip and knee are extremely
      effective procedures, resulting in decreased pain and improved function and
      quality of life in patients of all age groups including the elderly. The
      prevalence and use of TJR is increasing at a significant rate, therefore
      increased awareness of perioperative issues following TJR among health care
      providers is of paramount importance. Although elderly patients may be slightly
      more susceptible to perioperative complications, long-term success rates remain
      high, and careful perioperative monitoring and preventative measures have
      resulted in high rates of patient safety and few adverse outcomes in the elderly.

PMID- 20699166
TI  - Diet and exercise for obese adults with knee osteoarthritis.
AB  - Osteoarthritis (OA) is a common chronic disease and there is a need for
      treatments that can be provided for the course of the disease with minimal
      adverse side effects. Exercise is a safe intervention in patients with knee OA
      with few contraindications or adverse events. Obesity is the most modifiable risk
      factor for knee OA. The mechanisms by which obesity affects OA are of great
      concern to researchers and clinicians who manage this disease. This article
      reviews the physiologic and mechanical consequences of obesity and exercise on
      older adults with knee OA, the effects of long-term weight loss and exercise
      interventions, and the utility and feasibility of translating these results to
      clinical practice.

PMID- 20699170
TI  - Preface. Metabolic and endocrinopathic laminitis.

PMID- 20699171
TI  - Endocrinopathic laminitis.
AB  - In laminitis occurring in the field, as opposed to laminitis occurring during
      hospitalization or severe illness, endocrinopathic laminitis is the predominant
      form of laminitis. Prevalent causes of endocrinopathic laminitis are ECS and EMS.
      Exclusion of inflammatory or weight bearing causes of laminitis and focussing on
      the identification and treatment of underlying endocrine conditions will improve
      laminitis management strategies.

PMID- 20699172
TI  - Laminitis and the equine metabolic syndrome.
AB  - Although much has been written about laminitis in the context of its association
      with inflammatory processes, recognition is growing that most cases of laminitis
      examined by veterinarians in private practice are those associated with pasture
      grazing, obesity, and insulin resistance (IR). The term 'endocrinopathic
      laminitis' has been adopted to classify the instances of laminitis in which the
      origin seems to be more strongly associated with an underlying endocrinopathy,
      such as either IR or the influence of corticosteroids. Results of a recent study
      suggest that obesity and IR represent the most common metabolic and
      endocrinopathic predispositions for laminitis in horses. IR also plays an
      important role in the pathogenesis of laminitis that develops when some horses or
      ponies are allowed to graze pastures at certain times of the year. The term
      equine metabolic syndrome (EMS) has been proposed as a label for horses whose
      clinical examination results (including both physical examination and laboratory
      testing) suggest heightened risk for developing laminitis as a result of
      underlying IR.

PMID- 20699173
TI  - Hyperinsulinemic laminitis.
AB  - Laminitis occurring in association with hyperinsulinemia is frequently
      encountered in today's equine population. New evidence suggests that
      hyperinsulinemia is the direct cause of this form of laminitis, rather than
      insulin resistance per se. The mechanism by which elevated serum insulin
      concentrations result in lamellar dysfunction is currently under investigation by
      many researchers and the use of a new insulin infusion model for investigating
      the pathogenesis of insulin-associated laminitis will doubtless enhance progress
      in this field of research. By focusing on the metabolic and vascular actions of
      insulin in the lamellar microenvironment, our research group is trying to gain an
      insight into the pathophysiological processes involved in this complex problem,
      in order to better understand the disease.

PMID- 20699174
TI  - Current concepts on the pathophysiology of pasture-associated laminitis.
AB  - Epidemiologic studies indicate that most laminitis cases occur in horses and
      ponies kept at pasture, hence the term 'pasture-associated laminitis'. Clinical
      cases of laminitis most often occur under conditions that favor accumulation of
      rapidly fermentable nonstructural carbohydrates (fructans, simple sugars, or
      starches) in pasture, and animals with an equine metabolic syndrome (EMS)
      phenotype (insulin resistance, abnormal insulin dynamics, +/- obesity) seem to be
      at highest risk for developing the condition. Although the mechanisms linking
      consumption of pasture forage with development of lamellar failure have not been
      fully elucidated, a systemic inflammatory response that accompanies hindgut
      carbohydrate overload likely initiates lamellar inflammatory events (including
      infiltration and activation of leukocytes) that contribute to destruction of
      lamellar epithelium and extracellular matrix. This article reviews current
      knowledge on the epidemiology and risk factors for pasture-associated laminitis,
      including the role of forage carbohydrates and metabolic/endocrine
      predispositions, and also discusses the pathophysiology of this condition.

PMID- 20699175
TI  - Corticosteroid-associated laminitis.
AB  - A direct causal association between corticosteroid use and laminitis has yet to
      be proven scientifically, and there have been few studies specifically addressing
      this aspect. New evidence, however, is improving the understanding of the causes
      of laminitis, particularly related to endocrine factors. The focus of this
      article is discussing the circumstances under which steroids might cause this
      condition.

PMID- 20699176
TI  - Supporting limb laminitis.
AB  - Supporting limb laminitis poses a threat to all horses suffering from severe
      unilateral lameness. Despite its devastating effects, relatively little is known
      about the precise pathologic processes that lead to its development. This article
      reviews the potential mechanisms of supporting limb laminitis, and the authors
      present some preliminary data based on advanced imaging and computer-based
      modeling techniques aimed at further elucidating the etiology of this unique form
      of laminitis. Gaining a better understanding of the pathologic processes that
      lead to supporting limb laminitis is essential to enable the development of
      appropriate countermeasures to safeguard horses at risk of the disease.

PMID- 20699177
TI  - The pharmacologic basis for the treatment of endocrinopathic laminitis.
AB  - Although the treatment and management of laminitis in the horse requires a
      holistic and often multidisciplinary approach from the veterinarian, farrier, and
      nutritionist, this review focuses on pharmacologic interventions that might have
      prophylactic benefit, specifically in the horse with laminitis as a result of
      pituitary pars intermedia dysfunction and equine metabolic syndrome.

PMID- 20699178
TI  - Neuropathic pain management in chronic laminitis.
AB  - Managing pain in horses afflicted by chronic laminitis is one of the greatest
      challenges in equine clinical practice because it is the dreadful suffering of
      the animals that most often forces the veterinarian to end the battle with this
      disease. The purpose of this review is to summarize our current understanding of
      the complex mechanisms involved in generating and amplifying pain in animals with
      laminitis and, based on this information, to propose a modified approach to pain
      therapy. Furthermore, a recently developed pain scoring technique is presented
      that may help better quantify pain and the monitoring of responses to analgesic
      treatment in horses with laminitis.

PMID- 20699179
TI  - Digital venography in horses and its clinical application in Europe.
AB  - Clinical diagnostic venography allows in vivo visualization of the digital venous
      system and the effects of venocompression related to foot load and laminitis
      pathology. Venography has predictive potential and helps the clinician anticipate
      and treat laminitis tissue damage before it is detectable by plain radiography.
      The authors describe the podiatry radiographic technique to correctly perform
      digital venography and the modifications they have developed. The authors provide
      guidelines for the interpretation of laminitis venograms in the context of
      laminitis chronology. Frequent venographic monitoring of laminitis helps
      clinicians understand the sometimes puzzling chronology of the disease process
      and improves therapeutic outcome.

PMID- 20699180
TI  - Pasture management to minimize the risk of equine laminitis.
AB  - The sugar, starch, and fructan content (collectively referred to as nonstructural
      carbohydrates [NSC]) of pasture plants is dependent on the environmental
      conditions under which they have grown. Pasture that is stressed by cold,
      drought, or lack of nutrients can be 2 to 3 times higher in NSC than pasture that
      grows quickly in warm weather and is adequately watered and fertilized. Horses at
      risk for laminitis should have access to pasture limited or be removed completely
      when environmental conditions are conducive to high levels of NSC accumulation.

PMID- 20699181
TI  - Endocrinopathic laminitis: reducing the risk through diet and exercise.
AB  - Certain individual animals appear predisposed to recurrent pasture-associated
      laminitis, but the exact mechanisms underlying their predisposition remain a
      fundamental question in laminitis research. The risk of endocrinopathic laminitis
      can be reduced if steps are taken to improve insulin sensitivity and reduce
      inflammation using strategies based on exercise and diet. Exercise has been shown
      to reduce insulin resistance and suppress inflammation, and dietary manipulation
      can significantly affect insulin sensitivity.

PMID- 20699182
TI  - Field treatment and management of endocrinopathic laminitis in horses and ponies.
AB  - Endocrinopathic laminitis in horses and ponies has the potential to cause
      extensive damage to the feet before clinical signs of laminitis are apparent.
      Early diagnosis and intervention based on the detection and control of
      hyperinsulinemia are critical if the crippling changes that are seen in the
      disease are to be avoided. Preventing endocrinopathic laminitis, rather than
      treating it, is good practice management benefiting not only equine patients but
      also their owners.

PMID- 20699183
TI  - Clinical presentation, diagnosis, and prognosis of chronic laminitis in Europe.
AB  - The terminology relating to laminitis is confusing. This article describes how
      equine veterinarians, by using their eyes and fingers alone, can diagnose and
      evaluate a case of chronic laminitis. This evaluation will enable veterinarians
      to give a statistically significant prognosis that can be further refined by
      measurements taken from plain, weight-bearing lateromedial radiographs of the
      affected hooves. Should invasive techniques such as digital venography also be
      used, the results of both techniques are complementary.

PMID- 20699184
TI  - Farriery for chronic laminitis.
AB  - Laminitis is considered chronic once the distal phalanx has displaced within the
      hoof capsule. Chronic laminitis generally occurs as a direct sequel to acute
      laminitis. Clinical evaluation of chronic laminitis is best performed with a
      thorough clinical examination and radiography. The mainstay of hoof care is
      therapeutic farriery. In this article, the goals and principles of hoof care, the
      appropriate trim and various shoes that form the bulk of farriery for chronic
      laminitis, and surgical treatments are discussed.

PMID- 20699185
TI  - Chronic laminitis: foot management.
AB  - Laminitis is a disease of the suspensory apparatus of the distal phalanx, which
      can advance to the chronic stage with varying degrees of structural failure.
      Because the disease may ultimately lead to mechanical failure of the digit, a
      foot management plan is required to effectively and mechanically treat these
      cases. Many laminitis cases can be successfully rehabilitated back to athletic
      soundness, light use, breeding, or pasture soundness, whereas others suffer from
      permanent instability and never enjoy an acceptable level of comfort. To
      understand how to minimize damage in the acute laminitic foot or rehabilitate the
      chronic laminitic foot, the veterinarian should have an understanding of the
      normal supporting structures of the digit, the biomechanical forces acting on the
      foot, and the structural failure that results when these otherwise normal forces
      act on a diseased, damaged foot.

PMID- 20699186
TI  - Maggot debridement therapy for laminitis.
AB  - Maggot debridement therapy is a nontraumatic, minimally invasive method to treat
      infections in a foot compromised by chronic laminitis. A mechanical strategy must
      first be in place to address the instability of the distal phalanx and hoof
      capsule. Adverse reactions to maggot debridement therapy are uncommon and the
      only side effect observed has been irritation or hypersensitivity at the site.
      Chronic laminitic cases of sepsis/necrosis within the hoof benefit from this
      procedure due to the noninvasive, continuous debridement and healing properties
      provided by the larvae.

PMID- 20699187
TI  - First aid for the laminitic foot: therapeutic and mechanical support.
AB  - The goals of mechanical treatment during the acute phase of laminitis are to
      preserve the lamellar interface by reducing the forces that are compromising its
      integrity and to make the horse more comfortable. Early decision making is
      important in managing acute laminitis. This article helps the practitioner to
      identify some of the commonly used and accepted methods of protecting the
      laminitic foot. The materials available and the theories behind their use are
      also described. The laminitic foot needs to be understood before determining
      methods for its support. Most treatment options involve shifting the weight
      bearing forces from compromised areas of the foot (ie, the lamellar interface) to
      areas more capable of supporting the patient's weight, remembering that the sum
      of the forces should remain the same. The many treatment options available allow
      for flexibility and effective management and permit each modality to be combined
      in infinite ways for hoof support. The goal of therapy is to support the foot and
      stop the progression of the disease to the chronic phase.

PMID- 20699188
TI  - Evidence in wound prevention and treatment: are the 'rules' too hard?

PMID- 20699189
TI  - A practice-oriented recommendation for treatment of critically colonised and
      locally infected wounds using polihexanide.
AB  - The problem of wound infection presents a special challenge in the treatment of
      acute as well as chronic wounds. Typical complications not only jeopardise the
      successful outcome of treatment modalities as a whole; they may result in
      amputation or even become life-threatening. Polihexanide is an antimicrobial
      substance which is highly appropriate for use in critically colonised or infected
      acute and chronic wounds. This finding is based primarily on the broad
      antimicrobial spectrum and good cell and tissue compatibility of polihexanide,
      its capability of binding to organic matrix, the low risk of contact
      sensitisation, and the fact that it promotes wound healing. Furthermore, there
      has been no conclusive evidence to date of any pathogens developing resistances
      under the use of polihexanide. SUMMARY: Wound infections are special and
      challenging situations in therapy of acute and chronic wounds. Typical
      complications are risky not only for therapeutic process but also for amputation
      and viability of patients. Polihexanide is an exceedingly appropriate
      antimicrobial substance for using in critical colonised and local infected acute
      and chronic wounds. This evaluation is based on different properties of the
      compound like the broad antimicrobial spectrum, the excellent cell and tissue
      tolerability, the binding capacity to organic matrix, low risk of contact
      sensitisation and adjuvant effects to wound healing. Up to now there are no
      microbial resistances observed.

PMID- 20699190
TI  - Viral hijacking of the host ubiquitin system to evade interferon responses.
AB  - The post-translational attachment of ubiquitin or ubiquitin-like modifiers (ULMs)
      to proteins regulates many cellular processes including the generation of innate
      and adaptive immune responses to pathogens. Vice versa, pathogens counteract
      immune defense by inhibiting or redirecting the ubiquitination machinery of the
      host. A common immune evasion strategy is for viruses to target host
      immunoproteins for proteasomal or lysosomal degradation by employing viral or
      host ubiquitin ligases. By degrading key host adaptor and signaling molecules,
      viruses thus disable multiple immune response pathways including the production
      of and response to interferons as well as other innate host defense mechanisms.
      Recent work further revealed that viruses inhibit the ligation of ubiquitin or
      ULMs or remove ubiquitin from host cell proteins. Thus, viruses succeed in either
      stabilizing negative regulators of innate immune signaling or thwart host cell
      proteins that are activated by ubiquitin or ULM-modification.

PMID- 20699191
TI  - Levels of persistent organic pollutants and residual pattern of DDTs in small
      cetaceans from the coast of Sao Paulo, Brazil.
AB  - The State of Sao Paulo is the most developed area in Brazil and was impacted by
      persistent organic pollutants for several decades. This study investigated
      organochlorines in five species of small cetaceans (Pontoporia blainvillei,
      Stenella frontalis, Sotalia guianensis, Tursiops truncatus and Steno bredanensis)
      found dead along the coast of Sao Paulo between 1997 and 2003. DDTs (15.9 MUg g(
      1) lipid; mean for all pooled individuals) and PCBs (8.08 MUg g(-1)) exhibited
      the highest concentrations in the animals, reflecting large amounts formerly used
      in Brazil. Lower levels of mirex (0.149 MUg g(-1)), HCB (0.051 MUg g(-1)), CHLs
      (0.008 MUg g(-1)) and HCHs (0.007 MUg g(-1)) were detected in all species.
      Residual pattern of DDTs in dolphins suggests that o,p'-DDT is more recalcitrant
      than p,p'-DDT in the body of the animals and/or the environment. In contrast to
      p,p'-DDT, residues of o,p'-DDT seem to be preferentially converted into o,p'-DDD
      rather than o,p'-DDE.

PMID- 20699192
TI  - Microsporidiosis: Enterocytozoon bieneusi in domesticated and wild animals.
AB  - Microsporidia are a ubiquitous group of obligate intracellular parasites that
      infect all major animal groups. Enterocytozoon bieneusi is the most commonly
      identified Microsporidia in humans and has also been reported worldwide in
      animals with importance in veterinary medicine (e.g., cats, dogs, horses, cattle
      and pigs). The identification of E. bieneusi in animals has raised the question
      of the importance of animal reservoirs in the epidemiology of this pathogen, and
      the implications of the infection with this pathogen in infected animals.
      Considerable genetic diversity within E. bieneusi has been found with over 90
      genotypes identified based on the ITS nucleotide sequence of E. bieneusi spores
      recovered from the feces of infected humans and animals. Both host-adapted E.
      bieneusi genotypes with narrow host ranges and potentially zoonotic genotypes
      with wide host specificity have been identified. The information presented in
      this review should be useful in understanding the taxonomy, epidemiology,
      zoonotic potential, and importance in public health of E. bieneusi.

PMID- 20699193
TI  - Cyclothymic and hyperthymic temperaments may predict bipolarity in major
      depressive disorder: a supportive evidence for bipolar II1/2 and IV.
AB  - BACKGROUND: The concept of soft bipolar spectrum has not been fully confirmed.
      The aim of the present study is to investigate the validity of bipolar II1/2 and
      IV concept. METHODS: The subjects were 46 consecutive outpatients. The individual
      temperament of each patient was recorded using the Temperament Evaluation of
      Memphis, Pisa, Paris, and San Diego-Autoquestionnaire (TEMPS-A). The operational
      definition of bipolar II1/2 was those who had depression with cyclothymic
      temperament and that of bipolar IV was those who had depression with hyperthymic
      temperament. Finally, drug responses were investigated. RESULTS: DSM-IV-TR
      diagnoses were bipolar I (N=1), bipolar II (N=9), major depressive disorder
      (N=34) and depressive disorder not otherwise specified (N=2). Excluding one
      bipolar I patient, who had both cyclothymic and hyperthymic temperaments,
      patients with bipolar II1/2 (N=32) and IV (N=13) as well as bipolar II (N=9) were
      classified into the soft bipolar spectrum, although there was considerable
      overlap. The categorization of soft bipolar spectrum and unipolar depression
      significantly predicted depressive, cyclothymic, irritable, and anxious
      temperaments. Moreover, soft bipolar spectrum patients with lithium treatment
      were significantly more in remission than those without lithium treatment. In
      addition, more of those with selective serotonin reuptake inhibitors (SSRIs) had
      a significant tendency to lower remission than those without SSRIs. LIMITATIONS:
      This is a cross-sectional study with a relatively small number of subjects.
      CONCLUSIONS: The present findings suggest that cyclothymic and hyperthymic
      temperaments may predict bipolarity, and the validity of bipolar II1/2 and IV
      concept is supported.

PMID- 20699194
TI  - The Zuckerman-Kuhlman Personality Questionnaire predicts functioning styles of
      personality disorder: a trial in healthy subjects and personality-disorder
      patients.
AB  - Normal personality traits, as measured by the Zuckerman-Kuhlman Personality
      Questionnaire (ZKPQ), predicted some personality disorders in a sample of healthy
      volunteers. Whether these predictions could be more pronounced in patients with
      personality disorders remains unknown. We administered the ZKPQ and the Parker
      Personality Measure (PERM), which describes the functioning styles of personality
      disorder, in 134 patients with a range of personality disorders and in 268 age-,
      gender- and education level-matched healthy volunteers. Cluster A patients scored
      lowest on Sociability, cluster B highest on Impulsive Sensation Seeking and
      Aggression-Hostility, cluster C1 (Avoidant and Dependent types) highest on
      Neuroticism-Anxiety, and cluster C2 (Obsessive-Compulsive type) highest on
      Activity. Most of the predictors were consistent across both the healthy and
      patient groups. The variances that accounted for predicting most PERM styles by
      the ZKPQ traits in the patient group were higher than those in the healthy group.
      Our results showed that the ZKPQ traits could specifically predict the PERM
      styles in both healthy subjects and personality-disorder patients. This result
      was more pronounced in the latter group. The most powerful predictions were
      obtained for Antisocial, Dependent, Borderline and Avoidant styles, and the
      weakest for the Schizotypal and Schizoid styles in the patient group.

PMID- 20699195
TI  - Decreased plasma tryptophan and tryptophan/large neutral amino acid ratio in
      patients with neuroleptic-resistant schizophrenia: relationship to plasma
      cortisol concentration.
AB  - Tryptophan is the precursor of kynurenine and kynurenic acid, an alpha-7
      nicotinic acetylcholine receptor antagonist and a N-methyl-D-aspartate (NMDA)
      receptor antagonist, both of which have been implicated in schizophrenia (SCH),
      as well as of serotonin. Glucocorticoids can activate the tryptophan-kynurenine
      pathway and lower plasma tryptophan concentrations. Some previous studies have
      reported decreases in the plasma tryptophan concentration and the
      tryptophan/large neutral amino acid (LNAA) ratio, a measure reflecting the brain
      tryptophan concentration, in patients with SCH. However, the influence of plasma
      cortisol, which has been reported to be increased in patients with SCH, on plasma
      tryptophan levels has not been examined in prior studies. Thus, we examined
      plasma tryptophan concentrations, tryptophan/LNAA ratios, and their relationships
      with plasma cortisol concentrations in treatment-resistant SCH (TR-SCH) patients,
      in non-treatment-resistant SCH (NTR-SCH) patients, and in normal controls (NC).
      Plasma tryptophan concentrations were significantly lower in TR-SCH patients
      (n=74) than in NTR-SCH patients (n=85) and NC subjects (n=55). In addition,
      tryptophan/LNAA ratios were significantly lower in TR-SCH patients than in NC
      subjects. No difference was observed in either measure between NTR-SCH patients
      and NC subjects. Tryptophan/LNAA ratios and plasma tryptophan concentrations
      showed a significant negative correlation and a trend-level correlation,
      respectively, with plasma cortisol concentrations in TR-SCH patients, but not in
      NTR-SCH patients or in NC subjects. These results suggest the tryptophan
      kynurenine pathway may be particularly relevant to TR-SCH and that this may be
      influenced by the activity of the hypothalamic-pituitary-adrenal axis.

PMID- 20699196
TI  - Response surface modeling to predict biodiesel yield in a multi-feedstock
      biodiesel production plant.
AB  - For economic reasons, multi-feedstock plants are preferred to produce biodiesel.
      However, the optimal conditions of the transesterification reaction depend on the
      raw material, thus making difficult the achievement of a high yield of biodiesel
      when different types of feedstock are used under the same operational settings.
      In the present work, a response surface methodology is proposed to both predict
      biodiesel yield when different raw materials are used to produce biodiesel and to
      determine the optimal operational conditions of a multi-feedstock plant. The
      optimization of the transesterification reaction of five vegetable oils
      consisting in a wide range of fatty acid profiles has been carried out. Results
      provided a compromise zone where all the experimental responses satisfied the
      imposed specifications to achieve the goals, where the best optimal combination
      of parameters was selected. According to this model, the tested properties of the
      produced biodiesel are within the limits of the EN 14214 standard. It can be
      concluded that this methodology provides the most suitable operational conditions
      to achieve the highest biodiesel yield in a multi-feedstock biodiesel plant, also
      considering the economics of the process.

PMID- 20699197
TI  - Ischemic stroke in an adult with glycogen storage disease type I.
AB  - Glycogen Storage Disease Type I (GSD-I) is a metabolic disorder characterized by
      deficiency of glucose-6-phosphatase resulting in ineffective glycogen metabolism
      to glucose. These patients frequently have hyperlipidemia, among many other
      metabolic derangements. There is no consensus regarding the risk of developing
      atherosclerosis. We report an adult male with GSD-I who presented with cerebral
      infarction and a history of prior ischemic stroke and multiple coronary stent
      placements. We suggest that patients with GSD-I do have an increased risk of
      atherosclerosis and its complications and predict that these complications will
      be seen more frequently since patients with GSD-I are living longer as a result
      of better treatment.

PMID- 20699198
TI  - Amelioration of functional, biochemical and molecular deficits by
      epigallocatechin gallate in experimental model of alcoholic neuropathy.
AB  - Long term alcohol consumption leads to decreased nociceptive threshold
      characterized by spontaneous burning pain, hyperalgesia and allodynia. The
      mechanism involved in this pain includes increased oxidative-nitrosative stress,
      release of pro-inflammatory cytokines and neuronal apoptosis. The present study
      was designed to explore the protective effect of epigallocatechin-3-gallate
      against alcoholic neuropathic pain in rats. Rats fed with alcohol (35%) for 10
      weeks showed markedly decreased tail flick latency in tail-immersion test
      (thermal hyperalgesia), vocalization threshold in Randall-Sellito test
      (mechanical hyperalgesia) and paw-withdrawal threshold in von-Frey hair test
      (mechanical allodynia) along with enhanced oxidative-nitrosative stress and
      inflammatory mediators (TNF-alpha, IL-1beta and TGF-beta1 levels). Co
      administration of epigallocatechin-3-gallate (25-100 mg/kg) significantly and
      dose-dependently prevented functional, biochemical and molecular changes
      associated with alcoholic neuropathy. In conclusion, the current findings suggest
      the neuroprotective potential of epigallocatechin-3-gallate in attenuating the
      functional, biochemical and molecular alterations associated with alcoholic
      neuropathy through modulation of oxido-inflammatory cascade.

PMID- 20699199
TI  - Transfer of plasmid pJP4 from Escherichia coli and Pseudomonas putida to bacteria
      in activated sludge developed under different sludge retention times.
AB  - To add the knowledge on the plasmid-mediated bioaugmentation in the activated
      sludge process, conjugative transfer of a self-transmissible, broad host range,
      mercury resistance, and partial 2,4-dichlorophenoxyactic acid (2,4-D)-degrading
      plasmid pJP4 from Escherichia coli HB101 or Pseudomonas putida KT2440 to
      activated sludge bacteria were examined by filter mating. Activated sludge
      samples were collected from an actual wastewater treatment plant and laboratory
      reactors operated under different sludge retention times (SRTs) of 5, 10, and 15
      days. Transfer of pJP4 was observed in all combinations of donor and activated
      sludge (recipient) with the transfer frequency from 6.5 x 10-8 to 2.5 x 10-4
      transconjugants per recipient, except from E. coli HB101 to the activated sludge
      sample of SRT 5 days. Although plasmid pJP4 was transferred mainly to dominant
      bacteria belonging to Pseudomonas, the host range of pJP4 in the activated sludge
      varied depending on the donor strain. Phenotypically various transconjugants were
      isolated from activated sludge sampled from the reactors with longer SRT
      operations. All transconjugants exhibited high mercury resistance equivalent to
      the donor strains; some were capable of degrading 2,4-D. These results suggest
      that the behavior of plasmids can be controlled partially through selection of
      appropriate donor strains and operational conditions of the activated sludge
      process.

PMID- 20699200
TI  - COPII-mediated traffic in plants.
AB  - The secretory pathway encloses functionally interlinked organelles for the
      synthesis and deposition of most of the building blocks of eukaryotic cells, such
      as lipids, proteins and sugars. The coat protein complex II (COPII) is a
      specialized protein complex for the transport between secretory organelles,
      specifically from the endoplasmic reticulum (ER) to the Golgi apparatus. This
      review focuses on the developments on COPII research in the plant system. Here,
      we address the most recent advances in the distribution and regulation of ER-to
      Golgi protein transport intermediates and functional analyses of COPII isoforms.
      New studies support that such isoforms might not be functionally redundant and
      that they might have unanticipated roles in maintaining the integrity of the ER.

PMID- 20699201
TI  - Human behavior integration improves classification rates in real-time BCI.
AB  - Brain-computer interfaces (BCI) offer potential for individuals with a variety of
      motor and sensory disabilities to interact with their environment, communicate
      and control mobility aids. Two key factors which affect the performance of a BCI
      and its usability are the feedback given to the participant and the subject's
      motivation. This paper presents the results from a study investigating the
      effects of feedback and motivation on the performance of the Strathclyde Brain
      Computer Interface. The paper discusses how the performance of the system can be
      improved by behavior integration and human-in-the-loop design.

PMID- 20699203
TI  - Biometrically modulated collaborative control for an assistive wheelchair.
AB  - To operate a wheelchair, people with severe physical disabilities may require
      assistance, which can be provided by robotization. However, medical experts
      report that an excess of assistance may lead to loss of residual skills, so that
      it is important to provide just the right amount of assistance. This work
      proposes a collaborative control system based on weighting the robot's and the
      user's commands by their respective efficiency to reactively obtain an emergent
      controller. Thus, the better the person operates, the more control he/she gains.
      Tests with volunteers have proven, though, that some users may require extra
      assistance when they become stressed. Hence, we propose a controller that can
      change the amount of support taking into account supplementary biometric data. In
      this work, we use an off-the-shelf wearable pulse oximeter. Experiments have
      demonstrated that volunteers could use our wheelchair in a more efficient way due
      to the proposed biometric modulated collaborative control.

PMID- 20699202
TI  - Multimodal physical activity recognition by fusing temporal and cepstral
      information.
AB  - A physical activity (PA) recognition algorithm for a wearable wireless sensor
      network using both ambulatory electrocardiogram (ECG) and accelerometer signals
      is proposed. First, in the time domain, the cardiac activity mean and the motion
      artifact noise of the ECG signal are modeled by a Hermite polynomial expansion
      and principal component analysis, respectively. A set of time domain
      accelerometer features is also extracted. A support vector machine (SVM) is
      employed for supervised classification using these time domain features. Second,
      motivated by their potential for handling convolutional noise, cepstral features
      extracted from ECG and accelerometer signals based on a frame level analysis are
      modeled using Gaussian mixture models (GMMs). Third, to reduce the dimension of
      the tri-axial accelerometer cepstral features which are concatenated and fused at
      the feature level, heteroscedastic linear discriminant analysis is performed.
      Finally, to improve the overall recognition performance, fusion of the multimodal
      (ECG and accelerometer) and multidomain (time domain SVM and cepstral domain GMM)
      subsystems at the score level is performed. The classification accuracy ranges
      from 79.3% to 97.3% for various testing scenarios and outperforms the state-of
      the-art single accelerometer based PA recognition system by over 24% relative
      error reduction on our nine-category PA database.

PMID- 20699204
TI  - A realistic model for the analysis of heart magnetic stimulation.
AB  - The aim of the paper is the development of an accurate numerical model to compute
      the current density flowing through the heart of a virtual human body, and
      induced by an external electric or magnetic excitation. The model has been
      experimentally validated and then applied to investigate the main characteristics
      of the heart magnetic stimulation. This has been carried out by comparing the
      current density induced in the cardiac region by an external magnetic pulse with
      the corresponding quantity due to the more traditional electric source. Magnetic
      stimulation is studied because it offers some advantages: in fact, compared with
      the electrical stimulation, this technique is contactless and might allow the
      stimulation of a dressed patient. The design constraint of the whole system is
      represented by the current density, whose waveform and intensity are a compromise
      between the strength of the magnetic induction field and the pulse rise time.

PMID- 20699205
TI  - EMGTools, an adaptive and versatile tool for detailed EMG analysis.
AB  - We have developed an electromyography (EMG) decomposition system called EMGTools
      that can extract the constituent MUAPs and firing patterns (FPs) for quantitative
      analysis from the EMG signal recorded at slight effort for clinical evaluation.
      The aim was to implement a robust system able to handle the challenges and
      variations in clinically recorded signals. The system extracts MUAPs recorded by
      concentric needle electrodes and resolves superimposed MUAPs to produce FPs.
      Thus, critical fixed thresholds/parameters are avoided and replaced with adaptive
      solutions. The decomposition algorithm consists of three stages: segmentation,
      clustering, and resolution of compound segments. The results are validated using
      three different methods, comparing mean MUAP duration with previous methods,
      comparing dual channel recordings, and assessing the residual signal after
      decomposition. The advantages and limitations of the system are discussed.

PMID- 20699207
TI  - A new supervised method for blood vessel segmentation in retinal images by using
      gray-level and moment invariants-based features.
AB  - This paper presents a new supervised method for blood vessel detection in digital
      retinal images. This method uses a neural network (NN) scheme for pixel
      classification and computes a 7-D vector composed of gray-level and moment
      invariants-based features for pixel representation. The method was evaluated on
      the publicly available DRIVE and STARE databases, widely used for this purpose,
      since they contain retinal images where the vascular structure has been precisely
      marked by experts. Method performance on both sets of test images is better than
      other existing solutions in literature. The method proves especially accurate for
      vessel detection in STARE images. Its application to this database (even when the
      NN was trained on the DRIVE database) outperforms all analyzed segmentation
      approaches. Its effectiveness and robustness with different image conditions,
      together with its simplicity and fast implementation, make this blood vessel
      segmentation proposal suitable for retinal image computer analyses such as
      automated screening for early diabetic retinopathy detection.

PMID- 20699206
TI  - A macro finite-element formulation for cardiac electrophysiology simulations
      using hybrid unstructured grids.
AB  - Electrical activity in cardiac tissue can be described by the bidomain equations
      whose solution for large-scale simulations still remains a computational
      challenge. Therefore, improvements in the discrete formulation of the problem,
      which decrease computational and/or memory demands are highly desirable. In this
      study, we propose a novel technique for computing shape functions of finite
      elements (FEs). The technique generates macro FEs (MFEs) based on the local
      decomposition of elements into tetrahedral subelements with linear shape
      functions. Such an approach necessitates the direct use of hybrid meshes (HMs)
      composed of different types of elements. MFEs are compared to classic standard
      FEs with respect to accuracy and RAM memory usage under different scenarios of
      cardiac modeling, including bidomain and monodomain simulations in 2-D and 3-D
      for simple and complex tissue geometries. In problems with analytical solutions,
      MFEs displayed the same numerical accuracy of standard linear triangular and
      tetrahedral elements. In propagation simulations, conduction velocity and
      activation times agreed very well with those computed with standard FEs. However,
      MFEs offer a significant decrease in memory requirements. We conclude that HMs
      composed of MFEs are well suited for solving problems in cardiac computational
      electrophysiology.

PMID- 20699208
TI  - Adaptive imaging for lesion detection using a zoom-in PET system.
AB  - Positron emission tomography (PET) has become a leading modality in molecular
      imaging. Demands for further improvements in spatial resolution and sensitivity
      remain high with growing number of applications. In this paper we present a novel
      PET system design that integrates a high-resolution depth-of-interaction (DOI)
      detector into an existing PET system to obtain higher-resolution and higher
      sensitivity images in a target region around the face of the high-resolution
      detector. A unique feature of the proposed PET system is that the high-resolution
      detector can be adaptively positioned based on the detectability or quantitative
      accuracy of a feature of interest. This paper focuses on the signal-known
      exactly, background-known-exactly (SKE-BKE) detection task. We perform
      theoretical analysis of lesion detectability using computer observers, and then
      develop methods that can efficiently calculate the optimal position of the high
      resolution detector that maximizes the lesion detectability. We simulated
      incorporation of a high-resolution DOI detector into the microPET II scanner.
      Quantitative results verified that the new system has better performance than the
      microPET II scanner in terms of spatial resolution and lesion detectability, and
      that the optimal position for lesion detection can be reliably predicted by the
      proposed method.

PMID- 20699209
TI  - Simultaneous dual frequency 1H and 19F open coil imaging of arthritic rabbit knee
      at 3T.
AB  - The combination of sensitive magnetic resonance techniques with a selective site
      targeted nanoparticle contrast agent has a demonstrated utility for molecular
      imaging studies. By detecting a unique signature of the contrast agent, this
      approach can be employed to identify specific bio-molecular markers and observe
      cellular-level processes within a large and complex organism (e.g., in vivo
      rabbit). The objective of the present investigation was to design, fabricate and
      characterize a radio-frequency (RF) coil for the dual frequency ((1)H and (19)F)
      simultaneous collection of both nuclei images in a 3T field, in order to
      facilitate studies of arthritic knee degradation in rabbits. The coil supports
      both transmit and receive modes. The supporting activities included: 1)
      establishing a technical database for calculating the required coil parameters,
      2) selection of a favorable coil geometry, and 3) adaption of existing RF
      measurement techniques to the design, development and electrical evaluation of
      the coil. The coil is used in conjunction with a Philips Medical Systems clinical
      MRI scanner, requiring all RF simultaneous dual frequency ((1)H and (19)F) coils
      to operate in both transmit and receive modes. A commercial version of SPICE
      (simulation program with integrated circuit emphasis) was used to estimate
      significant operational parameters prior to fabricating the imaging coil.
      Excellent images were obtained with the fabricated coil and no operational
      problems were observed that would limit the use of other coil geometries and
      field strengths.

PMID- 20699210
TI  - Lightweight detection of additive watermarking in the DWT-domain.
AB  - This article aims at lightweight, blind detection of additive spread-spectrum
      watermarks in the DWT domain. We focus on two host signal noise models and two
      types of hypothesis tests for watermark detection. As a crucial point of our work
      we take a closer look at the computational requirements of watermark detectors.
      This involves the computation of the detection response, parameter estimation and
      threshold selection. We show that by switching to approximate host signal
      parameter estimates or even fixed parameter settings we achieve a remarkable
      improvement in runtime performance without sacrificing detection performance. Our
      experimental results on a large number of images confirm the assumption that
      there is not necessarily a tradeoff between computation time and detection
      performance.

PMID- 20699211
TI  - Constrained acquisition of ink spreading curves from printed color images.
AB  - Today's spectral reflection prediction models are able to predict the reflection
      spectra of printed color images with an accuracy as high as the reproduction
      variability allows. However, to calibrate such models, special uniform
      calibration patches need to be printed. These calibration patches use space and
      have to be removed from the final product. The present contribution shows how to
      deduce the ink spreading behavior of the color halftones from spectral
      reflectances acquired within printed color images. Image tiles of a color as
      uniform as possible are selected within the printed images. The ink spreading
      behavior is fitted by relying on the spectral reflectances of the selected image
      tiles. A relevance metric specifies the impact of each ink spreading curve on the
      selected image tiles. These relevance metrics are used to constrain the
      corresponding ink spreading curves. Experiments performed on an inkjet printer
      demonstrate that the new constraint-based calibration of the spectral reflection
      prediction model performs well when predicting color halftones significantly
      different from the selected image tiles. For some prints, the proposed image
      based model calibration is more accurate than a classical calibration.

PMID- 20699212
TI  - Applications of artificial intelligence in safe human-robot interactions.
AB  - The integration of industrial robots into the human workspace presents a set of
      unique challenges. This paper introduces a new sensory system for modeling,
      tracking, and predicting human motions within a robot workspace. A reactive
      control scheme to modify a robot's operations for accommodating the presence of
      the human within the robot workspace is also presented. To this end, a special
      class of artificial neural networks, namely, self-organizing maps (SOMs), is
      employed for obtaining a superquadric-based model of the human. The SOM network
      receives information of the human's footprints from the sensory system and infers
      necessary data for rendering the human model. The model is then used in order to
      assess the danger of the robot operations based on the measured as well as
      predicted human motions. This is followed by the introduction of a new reactive
      control scheme that results in the least interferences between the human and
      robot operations. The approach enables the robot to foresee an upcoming danger
      and take preventive actions before the danger becomes imminent. Simulation and
      experimental results are presented in order to validate the effectiveness of the
      proposed method.

PMID- 20699213
TI  - Supervised Gaussian process latent variable model for dimensionality reduction.
AB  - The Gaussian process latent variable model (GP-LVM) has been identified to be an
      effective probabilistic approach for dimensionality reduction because it can
      obtain a low-dimensional manifold of a data set in an unsupervised fashion.
      Consequently, the GP-LVM is insufficient for supervised learning tasks (e.g.,
      classification and regression) because it ignores the class label information for
      dimensionality reduction. In this paper, a supervised GP-LVM is developed for
      supervised learning tasks, and the maximum a posteriori algorithm is introduced
      to estimate positions of all samples in the latent variable space. We present
      experimental evidences suggesting that the supervised GP-LVM is able to use the
      class label information effectively, and thus, it outperforms the GP-LVM and the
      discriminative extension of the GP-LVM consistently. The comparison with some
      supervised classification methods, such as Gaussian process classification and
      support vector machines, is also given to illustrate the advantage of the
      proposed method.

PMID- 20699214
TI  - A practical approach to model selection for support vector machines with a
      Gaussian kernel.
AB  - When learning a support vector machine (SVM) from a set of labeled development
      patterns, the ultimate goal is to get a classifier attaining a low error rate on
      new patterns. This so-called generalization ability obviously depends on the
      choices of the learning parameters that control the learning process. Model
      selection is the method for identifying appropriate values for these parameters.
      In this paper, a novel model selection method for SVMs with a Gaussian kernel is
      proposed. Its aim is to find suitable values for the kernel parameter gamma and
      the cost parameter C with a minimum amount of central processing unit time. The
      determination of the kernel parameter is based on the argument that, for most
      patterns, the decision function of the SVM should consist of a sufficiently large
      number of significant contributions. A unique property of the proposed method is
      that it retrieves the kernel parameter as a simple analytical function of the
      dimensionality of the feature space and the dispersion of the classes in that
      space. An experimental evaluation on a test bed of 17 classification problems has
      shown that the new method favorably competes with two recently published methods:
      the classification of new patterns is equally good, but the computational effort
      to identify the learning parameters is substantially lower.

PMID- 20699215
TI  - Interoperability in digital electrocardiography: harmonization of ISO/IEEE x73
      PHD and SCP-ECG.
AB  - The ISO/IEEE 11073 (x73) family of standards is a reference frame for medical
      device interoperability. A draft for an ECG device specialization (ISO/IEEE 11073
      10406-d02) has already been presented to the Personal Health Device (PHD) Working
      Group, and the Standard Communications Protocol for Computer-Assisted
      ElectroCardioGraphy (SCP-ECG) Standard for short-term diagnostic ECGs
      (EN1064:2005+A1:2007) has recently been approved as part of the x73 family (ISO
      11073-91064:2009). These factors suggest the coordinated use of these two
      standards in foreseeable telecardiology environments, and hence the need to
      harmonize them. Such harmonization is the subject of this paper. Thus, a mapping
      of the mandatory attributes defined in the second draft of the ISO/IEEE 11073
      10406-d02 and the minimum SCP-ECG fields is presented, and various other
      capabilities of the SCP-ECG Standard (such as the messaging part) are also
      analyzed from an x73-PHD point of view. As a result, this paper addresses and
      analyzes the implications of some inconsistencies in the coordinated use of these
      two standards. Finally, a proof-of-concept implementation of the draft x73-PHD
      ECG device specialization is presented, along with the conversion from x73-PHD to
      SCP-ECG. This paper, therefore, provides recommendations for future
      implementations of telecardiology systems that are compliant with both x73-PHD
      and SCP-ECG.

PMID- 20699216
TI  - Public health in an era of personal health records: opportunities for innovation
      and new partnerships.
AB  - In the near future, citizens will be able to control and manage their own health
      information through electronic personal health record systems and tools. The
      clinical benefits of this innovation, such as cost savings, error reduction, and
      improved communication, have been discussed in the literature and public forums,
      as have issues related to privacy and confidentiality. Receiving little attention
      are the benefits these will have for public health. The benefits and potential
      for innovation are broad and speak directly to core public health functions such
      as health monitoring, outbreak management, empowerment, linking to services, and
      research. Coupled with this is a new relationship with citizens as key partners
      in protecting and promoting the public's health.

PMID- 20699217
TI  - Local prolactin is a target to prevent expansion of basal/stem cells in prostate
      tumors.
AB  - Androgen-independent recurrence is the major limit of androgen ablation therapy
      for prostate cancer. Identification of alternative pathways promoting prostate
      tumor growth is thus needed. Stat5 has been recently shown to promote human
      prostate cancer cell survival/proliferation and to be associated with early
      prostate cancer recurrence. Stat5 is the main signaling pathway triggered by
      prolactin (PRL), a growth factor whose local production is also increased in high
      grade prostate cancers. The first aim of this study was to use prostate-specific
      PRL transgenic mice to address the mechanisms by which local PRL induces prostate
      tumorogenesis. We report that (i) Stat5 is the major signaling cascade triggered
      by local PRL in the mouse dorsal prostate, (ii) this model recapitulates prostate
      tumorogenesis from precancer lesions to invasive carcinoma, and (iii)
      tumorogenesis involves dramatic accumulation and abnormal spreading of p63
      positive basal cells, and of stem cell antigen-1-positive cells identified as a
      stem/progenitor-like subpopulation. Because basal epithelial stem cells are
      proposed to serve as tumor-initiating cells, we challenged the relevance of local
      PRL as a previously unexplored therapeutic target. Using a double-transgenic
      approach, we show that Delta1-9-G129R-hPRL, a competitive PRL-receptor
      antagonist, prevented early stages of prostate tumorogenesis by reducing or
      inhibiting Stat5 activation, cell proliferation, abnormal basal-cell pattern, and
      frequency or grade of intraepithelial neoplasia. This study identifies PRL
      receptor/Stat5 as a unique pathway, initiating prostate tumorogenesis by altering
      basal-/stem-like cell subpopulations, and strongly supports the importance of
      further developing strategies to target locally overexpressed PRL in human
      prostate cancer.

PMID- 20699218
TI  - Ctr1 is an apical copper transporter in mammalian intestinal epithelial cells in
      vivo that is controlled at the level of protein stability.
AB  - Copper is an essential trace element that functions in a diverse array of
      biochemical processes that include mitochondrial respiration, neurotransmitter
      biogenesis, connective tissue maturation, and reactive oxygen chemistry. The Ctr1
      protein is a high-affinity Cu(+) importer that is structurally and functionally
      conserved in yeast, plants, fruit flies, and humans and that, in all of these
      organisms, is localized to the plasma membrane and intracellular vesicles.
      Although intestinal epithelial cell-specific deletion of Ctr1 in mice
      demonstrated a critical role for Ctr1 in dietary copper absorption, some
      controversy exists over the localization of Ctr1 in intestinal epithelial cells
      in vivo. In this work, we assess the localization of Ctr1 in intestinal
      epithelial cells through two independent mechanisms. Using immunohistochemistry,
      we demonstrate that Ctr1 localizes to the apical membrane in intestinal
      epithelial cells of the mouse, rat, and pig. Moreover, biotinylation of
      intestinal luminal proteins from mice fed a control or a copper-deficient diet
      showed elevated levels of both total and apical membrane Ctr1 protein in response
      to transient dietary copper limitation. Experiments in cultured HEK293T cells
      demonstrated that alterations in the levels of the glycosylated form of Ctr1 in
      response to copper availability were a time-dependent, copper-specific
      posttranslational response. Taken together, these results demonstrate apical
      localization of Ctr1 in intestinal epithelia across three mammalian species and
      suggest that increased Ctr1 apical localization in response to dietary copper
      limitation may represent an adaptive response to homeostatically modulate Ctr1
      availability at the site of intestinal copper absorption.

PMID- 20699219
TI  - A novel pax-like protein involved in transcriptional activation of cyst wall
      protein genes in Giardia lamblia.
AB  - Giardia lamblia differentiates into infectious cysts to survive outside of the
      host. It is of interest to identify factors involved in up-regulation of cyst
      wall proteins (CWPs) during this differentiation. Pax proteins are important
      regulators of development and cell differentiation in Drosophila and vertebrates.
      No member of this gene family has been reported to date in yeast, plants, or
      protozoan parasites. We have identified a pax-like gene (pax1) encoding a
      putative paired domain in the G. lamblia genome. Epitope-tagged Pax1 localized to
      nuclei during both vegetative growth and encystation. Recombinant Pax1
      specifically bound to the AT-rich initiator elements of the encystation-induced
      cwp1 to -3 and myb2 genes. Interestingly, overexpression of Pax1 increased cwp1
      to -3 and myb2 gene expression and cyst formation. Deletion of the C-terminal
      paired domain or mutation of the basic amino acids of the paired domain resulted
      in a decrease of the transactivation function of Pax1. Our results indicate that
      the Pax family has been conserved during evolution, and Pax1 could up-regulate
      the key encystation-induced genes to regulate differentiation of the protozoan
      eukaryote, G. lamblia.

PMID- 20699220
TI  - Influenza A virus polymerase inhibits type I interferon induction by binding to
      interferon beta promoter stimulator 1.
AB  - Type I interferons (IFNs) are known to be critical factors in the activation of
      host antiviral responses and are also important in protection from influenza A
      virus infection. Especially, the RIG-I- and IPS-1-mediated intracellular type I
      IFN-inducing pathway is essential in the activation of antiviral responses in
      cells infected by influenza A virus. Previously, it has been reported that
      influenza A virus NS1 is involved in the inhibition of this pathway. We show in
      this report that the influenza A virus utilizes another critical inhibitory
      mechanism in this pathway. In fact, the viral polymerase complex exhibited an
      inhibitory activity on IFNbeta promoter activation mediated by RIG-I and IPS-1,
      and this activity was not competitive with the function of NS1. Co
      immunoprecipitation analysis revealed that each polymerase subunit bound to IPS-1
      in mammalian cells, and each subunit inhibited the activation of IFNbeta promoter
      by IPS-1 independently. In addition, by a combinational expression of each
      polymerase subunit, IPS-1-induced activation of IFNbeta promoter was more
      efficiently inhibited by the expression of PB2 or PB2-containing complex.
      Moreover, the expression of PB2 inhibited the transcription of the endogenous
      IFNbeta gene induced after influenza A virus infection. These findings
      demonstrate that the viral polymerase plays an important role for regulating host
      anti-viral response through the binding to IPS-1 and inhibition of IFNbeta
      production.

PMID- 20699221
TI  - Anti-apoptotic protein BCL2 down-regulates DNA end joining in cancer cells.
AB  - Cancer cells are often associated with secondary chromosomal rearrangements, such
      as deletions, inversions, and translocations, which could be the consequence of
      unrepaired/misrepaired DNA double strand breaks (DSBs). Nonhomologous DNA end
      joining is one of the most common pathways to repair DSBs in higher eukaryotes.
      By using oligomeric DNA substrates mimicking various endogenous DSBs in a cell
      free system, we studied end joining (EJ) in different cancer cell lines. We found
      that the efficiency of EJ varies among cancer cells; however, there was no
      remarkable difference in the mechanism and expression of EJ proteins.
      Interestingly, cancer cells with lower levels of EJ possessed elevated expression
      of BCL2 and vice versa. Removal of BCL2 by immunoprecipitation or protein
      fractionation led to elevated EJ. More importantly, we show that overexpression
      of BCL2 or the addition of purified BCL2 led to the down-regulation of EJ.
      Further, we found that BCL2 interacts with KU proteins both in vitro and in vivo.
      Hence, our results suggest that EJ in cancer cells could be negatively regulated
      by the anti-apoptotic protein, BCL2, and this may contribute toward increased
      chromosomal abnormalities in cancer.

PMID- 20699222
TI  - Molecular mapping of the RNA Cap 2'-O-methyltransferase activation interface
      between severe acute respiratory syndrome coronavirus nsp10 and nsp16.
AB  - Several protein-protein interactions within the SARS-CoV proteome have been
      identified, one of them being between non-structural proteins nsp10 and nsp16. In
      this work, we have mapped key residues on the nsp10 surface involved in this
      interaction. Alanine-scanning mutagenesis, bioinformatics, and molecular modeling
      were used to identify several "hot spots," such as Val(42), Met(44), Ala(71),
      Lys(93), Gly(94), and Tyr(96), forming a continuous protein-protein surface of
      about 830 A(2), bearing very conserved amino acids among coronaviruses. Because
      nsp16 carries RNA cap 2'-O-methyltransferase (2'O-MTase) activity only in the
      presence of its interacting partner nsp10 (Bouvet, M., Debarnot, C., Imbert, I.,
      Selisko, B., Snijder, E. J., Canard, B., and Decroly, E. (2010) PLoS Pathog. 6,
      e1000863), functional consequences of mutations on this surface were evaluated
      biochemically. Most changes that disrupted the nsp10-nsp16 interaction without
      structural perturbations were shown to abrogate stimulation of nsp16 RNA cap 2'O
      MTase activity. More strikingly, the Y96A mutation abrogates stimulation of nsp16
      2'O-MTase activity, whereas Y96F overstimulates it. Thus, the nsp10-nsp16
      interface may represent an attractive target for antivirals against human and
      animal pathogenic coronaviruses.

PMID- 20699223
TI  - Yeast 18 S rRNA is directly involved in the ribosomal response to stringent AUG
      selection during translation initiation.
AB  - In eukaryotes, the 40 S ribosomal subunit serves as the platform of initiation
      factor assembly, to place itself precisely on the AUG start codon. Structural
      arrangement of the 18 S rRNA determines the overall shape of the 40 S subunit.
      Here, we present genetic evaluation of yeast 18 S rRNA function using 10 point
      mutations altering the polysome profile. All the mutants reduce the abundance of
      the mutant 40 S, making it limiting for translation initiation. Two of the
      isolated mutations, G875A, altering the core of the platform domain that binds
      eIF1 and eIF2, and A1193U, changing the h31 loop located below the P-site
      tRNA(i)(Met), show phenotypes indicating defective regulation of AUG selection.
      Evidence is provided that these mutations reduce the interaction with the
      components of the preinitiation complex, thereby inhibiting its function at
      different steps. These results indicate that the 18 S rRNA mutations impair the
      integrity of scanning-competent preinitiation complex, thereby altering the 40 S
      subunit response to stringent AUG selection. Interestingly, nine of the mutations
      alter the body/platform domains of 18 S rRNA, potentially affecting the bridges
      to the 60 S subunit, but they do not change the level of 18 S rRNA intermediates.
      Based on these results, we also discuss the mechanism of the selective
      degradation of the mutant 40 S subunits.

PMID- 20699224
TI  - Novel importin-alpha family member Kpna7 is required for normal fertility and
      fecundity in the mouse.
AB  - Nuclear importing system and nuclear factors play important roles in mediating
      nuclear reprogramming and zygotic gene activation. However, the components and
      mechanisms that mediate nuclearly specific targeting of the nuclear proteins
      during nuclear reprogramming and zygotic gene activation remain largely unknown.
      Here, we identified a novel member of the importin-alpha family, AW146299(KPNA7),
      which is predominantly expressed in mouse oocytes and zygotes and localizes to
      the nucleus or spindle. Mutation of Kpna7 gene caused reproductivity reduction
      and sex imbalance by inducing preferential fetal lethality in females.
      Parthenogenesis analysis showed that the cell cycle of activated one-cell embryos
      is loss of control and ahead of schedule but finally failed to develop into
      blastocyst stage. Further RT-PCR and epigenetic modification analysis showed that
      knocking out of Kpna7 induced abnormalities of gene expression (dppa2, dppa4, and
      piwil2) and epigenetic modifications (down-regulation of histone H3K27me3).
      Biochemical analysis showed that KPNA7 interacts with KPNB1 (importin-beta1). In
      summary, we identified a novel Kpna7 gene that is required for normal fertility
      and fecundity.

PMID- 20699225
TI  - Lipid raft association and cholesterol sensitivity of P2X1-4 receptors for ATP:
      chimeras and point mutants identify intracellular amino-terminal residues
      involved in lipid regulation of P2X1 receptors.
AB  - Cholesterol-rich lipid rafts act as signaling microdomains and can regulate
      receptor function. We have shown in HEK293 cells recombinant P2X1-4 receptors
      (ATP-gated ion channels) are expressed in lipid rafts. Localization to flotillin
      rich lipid rafts was reduced by the detergent Triton X-100. This sensitivity to
      Triton X-100 was concentration- and subunit-dependent, demonstrating differential
      association of P2X1-4 receptors with lipid rafts. The importance of raft
      association to ATP-evoked P2X receptor responses was determined in patch clamp
      studies. The cholesterol-depleting agents methyl-beta-cyclodextrin or filipin
      disrupt lipid rafts and reduced P2X1 receptor currents by >90%. In contrast, ATP
      evoked P2X2-4 receptor currents were unaffected by lipid raft disruption. To
      determine the molecular basis of cholesterol sensitivity, we generated chimeric
      receptors replacing portions of the cholesterol-sensitive P2X1 receptor with the
      corresponding region from the insensitive P2X2 receptor. These chimeras
      identified the importance of the intracellular amino-terminal region between the
      conserved protein kinase C site and the first transmembrane segment for the
      sensitivity to cholesterol depletion. Mutation of any of the variant residues
      between P2X1 and P2X2 receptors in this region in the P2X1 receptor (residues 20
      23 and 27-29) to cysteine removed cholesterol sensitivity. Cholesterol depletion
      did not change the ATP sensitivity or cell surface expression of P2X1 receptors.
      This suggests that cholesterol is normally needed to facilitate the
      opening/gating of ATP-bound P2X1 receptor channels, and mutations in the pre
      first transmembrane segment region remove this requirement.

PMID- 20699226
TI  - Kinetics of re-establishing H3K79 methylation marks in global human chromatin.
AB  - We employ a stable isotope strategy wherein both histones and their methylations
      are labeled in synchronized human cells. This allows us to differentiate between
      old and new methylations on pre-existing versus newly synthesized histones. The
      strategy is implemented on K79 methylation in an isoform-specific manner for
      histones H3.1, H3.2, and H3.3. Although levels of H3.3K79 monomethylation are
      higher than that of H3.2/H3.1, the rate of establishing the K79 methylation is
      the same for all three isoforms. Surprisingly, we find that pre-existing "old"
      histones continue to be K79-monomethylated and -dimethylated at a rate equal to
      the newly synthesized histones. These observations imply that some degree of
      positional "scrambling" of K79 methylation occurs through the cell cycle.

PMID- 20699227
TI  - Renal cancer resistance to antiangiogenic therapy is delayed by restoration of
      angiostatic signaling.
AB  - Treatment of metastatic renal cell cancer (RCC) with antiangiogenic agents that
      block vascular endothelial growth factor (VEGF) receptor 2 signaling produces
      tumor regression in a substantial fraction of patients; however, resistance
      typically develops within 6 to 12 months. The purpose of this study was to
      identify molecular pathways involved in resistance. Treatment of mice bearing
      either 786-0 or A498 human RCC xenografts with sorafenib or sunitinib produced
      tumor growth stabilization followed by regrowth despite continued drug
      administration analogous to the clinical experience. Tumors and plasma were
      harvested at day 3 of therapy and at the time of resistance to assess pathways
      that may be involved in resistance. Serial perfusion imaging, and plasma and
      tumor collections were obtained in mice treated with either placebo or sunitinib
      alone or in combination with intratumoral injections of the angiostatic chemokine
      CXCL9. Sunitinib administration led to an early downmodulation of IFNgamma levels
      as well as reduction of IFNgamma receptor and downstream angiostatic chemokines
      CXCL9 to 11 within the tumor. Intratumoral injection of CXCL9, although producing
      minimal effects by itself, when combined with sunitinib resulted in delayed
      resistance in vivo accompanied by a prolonged reduction of microvascular density
      and tumor perfusion as measured by perfusion imaging relative to sunitinib alone.
      These results provide evidence that resistance to VEGF receptor therapy is due at
      least in part to resumption of angiogenesis in association with reduction of
      IFNgamma-related angiostatic chemokines, and that this resistance can be delayed
      by concomitant administration of CXCL9.

PMID- 20699229
TI  - Working memory load modulates distractor competition in primary visual cortex.
AB  - When stimuli compete for sensory processing and response selection, coherent goal
      guided behavior requires cognitive control so that task-relevant "targets" rather
      than irrelevant distractors are selected. It has been shown that reduced
      cognitive control under high working memory load increases distractor competition
      for selection. It remains unknown, though, whether cognitive control by working
      memory has an effect on the earliest levels of sensory processing in primary
      visual cortex. The present study addressed this question by having subjects
      perform a selective attention task involving classification of meaningful target
      objects while also ignoring congruent and incongruent distractor images. The
      level of cognitive control over distractor competition was varied through a
      concurrent working memory task of either low (1 digit) or high (6 digits) load.
      Functional magnetic resonance imaging revealed greater distractor competition
      effects not only on behavior but also on the sensory correlates in primary visual
      cortex (areas V1-V2) in conditions of high (vs. low) working memory load. In
      addition, high working memory load resulted in increased congruency-related
      functional connectivity between anterior cingulate cortex and V1. These results
      are the first to establish the neural correlates of distractor competition
      effects in primary visual cortex and the critical role of working memory in their
      cognitive control.

PMID- 20699230
TI  - VIP, CRF, and PACAP act at distinct receptors to elicit different cAMP/PKA
      dynamics in the neocortex.
AB  - The functional significance of diverse neuropeptide coexpression and convergence
      onto common second messenger pathways remains unclear. To address this question,
      we characterized responses to corticotropin-releasing factor (CRF), pituitary
      adenylate cyclase-activating peptide (PACAP), and vasoactive intestinal peptide
      (VIP) in rat neocortical slices using optical recordings of cyclic adenosine
      monophosphate (cAMP) and protein kinase A (PKA) sensors, patch-clamp, and single
      cell reverse transcription-polymerase chain reaction. Responses of pyramidal
      neurons to the 3 neuropeptides markedly differed in time-course and amplitude.
      Effects of these neuropeptides on the PKA-sensitive slow afterhyperpolarization
      current were consistent with those observed with cAMP/PKA sensors. CRF-1
      receptors, primarily expressed in pyramidal cells, reportedly mediate the
      neocortical effects of CRF. PACAP and VIP activated distinct PAC1 and VPAC1
      receptors, respectively. Indeed, a selective VPAC1 antagonist prevented VIP
      responses but had a minor effect on PACAP responses, which were mimicked by a
      specific PAC1 agonist. While PAC1 and VPAC1 were coexpressed in pyramidal cells,
      PAC1 expression was also frequently detected in interneurons, suggesting that
      PACAP has widespread effects on the neuronal network. Our results suggest that
      VIP and CRF, originating from interneurons, and PACAP, expressed mainly by
      pyramidal cells, finely tune the excitability and gene expression in the
      neocortical network via distinct cAMP/PKA-mediated effects.

PMID- 20699231
TI  - Population genetic relationships between Casearia sylvestris (Salicaceae)
      varieties occurring sympatrically and allopatrically in different ecosystems in
      south-east Brazil.
AB  - BACKGROUND AND AIMS: Species delimitation can be problematic, and recently
      diverged taxa are sometimes viewed as the extremes of a species' continuum in
      response to environmental conditions. Using population genetic approaches, this
      study assessed the relationship between two Casearia sylvestris (Salicaceae)
      varieties, which occur sympatrically and allopatrically in the landscape of south
      east Brazil, where intermediate types are also found. METHODS: In total, 376
      individuals from nine populations in four different ecosystems were sampled, and
      nine microsatellite markers were used to assess the relative effects of the
      ecosystems and varieties on the distribution of genetic diversity among
      populations of this species. KEY RESULTS: As a by-product of this study, several
      PCR products with more than two alleles were observed. The possibility that extra
      bands represent non-specific amplification or PCR artefacts was discarded by
      sequencing a sample of these bands. We suggest that (partial) genome duplication
      in C. sylvestris most probably explains this phenomenon, which may be a key
      factor in the differentiation of the two taxa, as it was markedly more frequent
      in one of the varieties. AMOVA indicated that approx. 22 % of the total genetic
      diversity was found between the two varieties. Bayesian analysis identified
      varieties and ecosystems as evolutionary units, rather than the individual
      populations sampled. CONCLUSIONS: The results are in agreement with field
      observations and support the recognition of two varieties, as well as documenting
      the occurrence of hybridization between them.

PMID- 20699232
TI  - Implementation of multivariate control charts in a clinical setting.
AB  - BACKGROUND: In most clinical monitoring cases there is a need to track more than
      one quality characteristic. If separate univariate charts are used, the overall
      probability of a false alarm may be inflated since correlation between variables
      is ignored. In such cases, multivariate control charts should be considered.
      PURPOSE: This paper considers the implementation and performance of the T(2),
      multivariate exponentially weighted moving average (MEWMA) and multivariate
      cumulative sum (MCUSUM) charts in light of the challenges faced in clinical
      settings. We discuss how to handle incomplete records and non-normality of data,
      and we provide recommendations on chart selection. DATA SOURCES: Our discussion
      is supported by a case study involving the monitoring of radiation delivered to
      patients undergoing diagnostic coronary angiogram procedures at St Andrew's War
      Memorial Hospital, Australia. We also perform a simulation study to investigate
      chart performance for various correlation structures, patterns of mean shifts,
      amounts of missing data and methods of imputation. CONCLUSIONS: The MEWMA and
      MCUSUM charts detect small to moderate shifts quickly, even when the quality
      characteristics are uncorrelated. The T(2) chart performs less well overall,
      although it is useful for rapid detection of large shifts. When records are
      incomplete, we recommend using multiple imputation.

PMID- 20699233
TI  - The current state of patient safety culture in Lebanese hospitals: a study at
      baseline.
AB  - OBJECTIVE: The objective of this study is to conduct a baseline assessment of
      patient safety culture in Lebanese hospitals. DESIGN: The study adopted a cross
      sectional research design and utilized the hospital survey on patient safety
      culture (HSOPSC). SETTING: Sixty-eight Lebanese hospitals participated in the
      study (54% of all hospitals). PARTICIPANTS: A total of 6807 hospital employees
      participated in the study including hospital-employed physicians, nurses,
      clinical and non-clinical staff, and others. MAIN OUTCOME MEASURES: The HSOPSC
      measures 12 composites of patient safety culture. Two of the composites
      (frequency of events reported and overall perception of safety), in addition to
      questions on patient safety grade and number of events reported, are the four
      outcome variables. RESULTS: Survey respondents were primarily employed in medical
      and surgical units. The dimensions with the highest positive ratings were
      teamwork within units, hospital management support for patient safety, and
      organizational learning and continuous improvement, while those with lowest
      ratings included staffing and non-punitive response to error. Approximately 60%
      of respondents reported not completing any event reports in the past 12 months
      and over 70% gave their hospitals an 'excellent/very good' patient safety grade.
      Bivariate and multivariate analysis revealed significant differences across
      hospitals of different size and accreditation status. CONCLUSIONS: Study findings
      provide evidence that can be used by policy makers, managers and leaders who are
      able to create the culture and commitment needed to identify and solve underlying
      systemic causes related to patient safety.

PMID- 20699234
TI  - Apoptosis-induced histone H3 methylation is targeted by autoantibodies in
      systemic lupus erythematosus.
AB  - OBJECTIVES: In systemic lupus erythematosus (SLE) apoptotic chromatin is present
      extracellularly, which is most likely the result of disturbed apoptosis and/or
      insufficient removal. Released chromatin, modified during apoptosis, activates
      the immune system resulting in the formation of autoantibodies. A study was
      undertaken to identify apoptosis-induced histone modifications that play a role
      in SLE. METHODS: The lupus-derived monoclonal antibody BT164, recently
      established by selection using apoptotic nucleosomes, was analysed by ELISA,
      western blot analysis and immunofluorescence staining using chromatin, cells,
      plasma and renal sections. Random peptide phage display and peptide inhibition
      ELISA were used to identify precisely the epitope of BT164. The reactivity of
      plasma samples from lupus mice and patients with SLE with the epitope of BT164
      was investigated by peptide ELISA. RESULTS: The epitope of BT164 was mapped in
      the N-terminal tail of histone H3 (27-KSAPAT-32) and included the apoptosis
      induced trimethylation of K27. siRNA-mediated silencing of histone demethylases
      in cultured cells resulted in hypermethylation of H3K27 and increased nuclear
      reactivity of BT164. This apoptosis-induced H3K27me3 is a target for
      autoantibodies in patients and mice with SLE and is present in plasma and in
      glomerular deposits. CONCLUSION: In addition to previously identified acetylation
      of histone H4, H2A and H2B, this study shows that trimethylation of histone H3 on
      lysine 27 is induced by apoptosis and associated with autoimmunity in SLE. This
      finding is important for understanding the autoimmune response in SLE and for the
      development of translational strategies.

PMID- 20699235
TI  - Autoantibodies in twins discordant for rheumatoid arthritis.

PMID- 20699236
TI  - Skewed X chromosomal inactivation impacts T regulatory cell function in systemic
      sclerosis.
AB  - OBJECTIVES: > To investigate the role of X chromosomal inactivation (XCI) in
      systemic sclerosis (SSc) and its effects on forkhead box P3 (Foxp3) expression in
      T regulatory cells (Tregs). METHODS: 217 women with SSc and 107 healthy women
      (controls) were included in the study. From these subjects, DNA was isolated from
      total peripheral blood mononuclear cells, plasmacytoid dendritic cells, T cells,
      B cells, myeloid dendritic cells and monocytes after magnetic bead separation.
      All samples were assessed for skewed XCI patterns with the Human Androgen
      Receptor Assay. The outcome was assessed by linear regression. CD4+ CD25+ cells
      were then isolated and intracellular Foxp3 expression was assessed by flow
      cytometry. RESULTS: Skewing was not associated with increased age in patients
      with SSc, in contrast to the control population (r = 0.45, p < 0.0001). Taking
      this into account, a significantly higher frequency of skewed XCI was found in
      patients with SSc compared with controls (p = 0.001). No difference in skewing
      was observed between the immune cell subsets. In addition, a higher concentration
      of Foxp3+ cells exhibiting a lower Foxp3 mean fluorescence intensity was found in
      the patients with SSc, with profound XCI skewing (both p < 0.001) associated with
      less efficient suppressive activity (p=0.012). CONCLUSIONS: Skewed XCI plays a
      role in susceptibility to SSc, is not restricted and influences Foxp3 expression
      and the suppressive capacity of Tregs.

PMID- 20699237
TI  - Are there specific genetic risk factors for the different forms of ANCA
      associated vasculitis?

PMID- 20699238
TI  - Joint destruction in early rheumatoid arthritis over 8 years is similar in women
      and men despite apparently higher disease activity and poorer function in women.

PMID- 20699239
TI  - The American College of Rheumatology/European League Against Rheumatism Criteria
      for the classification of rheumatoid arthritis: a game changer.

PMID- 20699240
TI  - A welcome address for the new criteria.

PMID- 20699242
TI  - The 2010 American College of Rheumatology/European League Against Rheumatism
      classification criteria for rheumatoid arthritis: methodological report phase I.
AB  - OBJECTIVE: To apply a data-driven approach to investigate, in patients newly
      presenting with undifferentiated inflammatory synovitis, key variables that
      discriminate the subset of patients at sufficiently high risk of persistent or
      erosive disease for the purpose of developing new criteria for rheumatoid
      arthritis (RA). METHODS: In this first phase of the collaborative effort of the
      American College of Rheumatology and European League Against Rheumatism to
      develop new criteria for RA, a pooled analysis of early arthritis cohorts made
      available by the respective investigators is presented. All the variables
      associated with the gold standard of treatment with methotrexate during the first
      year after enrolment were first identified. Principal component analysis was then
      used to identify among the significant variables those sets that represent
      similar domains. In a final step, from each domain one representative variable
      was extracted, all of which were then tested for their independent effects in a
      multivariate regression model. From the OR in that final model, the relative
      weight of each variable was estimated. RESULTS: The final domains and variables
      identified by this process (and their relative weights) were: swelling of a
      metacarpophalangeal joint (MCP; 1.5), swelling of a proximal interphalangeal
      joint (PIP; 1.5), swelling of the wrist (1.5), tenderness of the hand (ie, MCP,
      PIP or wrist (2)), acute phase reaction (ie, C reactive protein or erythrocyte
      sedimentation rate and weights for moderate or high elevations of either one (1
      for moderate, 2 for high elevation)) and serological abnormalities (ie,
      rheumatoid factors or anti-citrullinated protein antibodies, again with separate
      weights for moderate or high elevations (2 and 4, respectively)). CONCLUSION: The
      results of this first phase were subsequently used in the second phase of the
      project, which is reported in a separate methodological paper, and for derivation
      of the final set of criteria.

PMID- 20699241
TI  - 2010 rheumatoid arthritis classification criteria: an American College of
      Rheumatology/European League Against Rheumatism collaborative initiative.
AB  - OBJECTIVE: The 1987 American College of Rheumatology (ACR; formerly the American
      Rheumatism Association) classification criteria for rheumatoid arthritis (RA)
      have been criticised for their lack of sensitivity in early disease. This work
      was undertaken to develop new classification criteria for RA. METHODS: A joint
      working group from the ACR and the European League Against Rheumatism developed,
      in three phases, a new approach to classifying RA. The work focused on
      identifying, among patients newly presenting with undifferentiated inflammatory
      synovitis, factors that best discriminated between those who were and those who
      were not at high risk for persistent and/or erosive disease--this being the
      appropriate current paradigm underlying the disease construct 'RA'. RESULTS: In
      the new criteria set, classification as 'definite RA' is based on the confirmed
      presence of synovitis in at least one joint, absence of an alternative diagnosis
      better explaining the synovitis, and achievement of a total score of 6 or greater
      (of a possible 10) from the individual scores in four domains: number and site of
      involved joints (range 0-5), serological abnormality (range 0-3), elevated acute
      phase response (range 0-1) and symptom duration (two levels; range 0-1).
      CONCLUSION: This new classification system redefines the current paradigm of RA
      by focusing on features at earlier stages of disease that are associated with
      persistent and/or erosive disease, rather than defining the disease by its late
      stage features. This will refocus attention on the important need for earlier
      diagnosis and institution of effective disease-suppressing therapy to prevent or
      minimise the occurrence of the undesirable sequelae that currently comprise the
      paradigm underlying the disease construct 'RA'.

PMID- 20699243
TI  - Therapeutic opportunities in systemic lupus erythematosus: state of the art and
      prospects for the new decade.
AB  - Immune responses against endogenous nuclear antigens are characteristic of
      systemic lupus erythematosus (SLE), a highly pleiomorphic disease predominantly
      affecting young women of reproductive age. Genome-wide association studies have
      confirmed the importance of genes associated with the immune response as well as
      genes involved in endothelial function and tissue response to injury. Immune
      complexes, autoantibodies, complement, cytokines, endothelial injury and a
      thrombophilic state associated with antiphospholipid antibodies are important for
      mediating tissue dysfunction. If not treated promptly, a significant proportion
      of patients-especially those with more aggressive disease-accumulate irreversible
      damage. During the past decade, novel combinations of immunosuppressive drugs and
      biologicals have been added to the therapeutic armamentarium. At the same time,
      the emphasis in the management of lupus has shifted from individual drugs to a
      strategy that aims at early, sustained remission tailored to disease
      manifestations and severity with the lowest possible toxicity. Infections and
      accelerated atherosclerosis (attributed to both traditional and non-traditional
      risk factors) and thrombosis-related clinical events (including arterial, venous
      and pregnancy loss) represent a major challenge in the management of the disease.
      To avoid fragmentation and optimise medical care, evidence and expert-based
      recommendations have been developed. For the future the authors predict a new
      taxonomy on the basis of mechanisms rather than clinical empiricism, leading to
      targeted therapy.

PMID- 20699244
TI  - Characterization of plasmid-mediated lincosamide resistance in a field isolate of
      Haemophilus parasuis.

PMID- 20699245
TI  - Broad-spectrum antibiotic resistance of Planctomycetes organisms determined by
      Etest.
AB  - OBJECTIVES: The in vitro susceptibility of Planctomycetes organisms to
      antibiotics has seldom been studied and when it has, a variety of methods have
      been used. The objective of the study was to expand the knowledge of
      Planctomycetes antibiotic susceptibility patterns. METHODS: Planctomyces maris,
      Planctomyces brasiliensis, Blastopirellula marina, Planctomyces limnophilus,
      Gemmata obscuriglobus and Rhodopirellula baltica reference strains were tested
      for in vitro susceptibility to 18 antibiotics, representing 11 antibiotic
      families, using the Etest method. RESULTS: All Planctomycetes organisms were
      found to be resistant to beta-lactams, with MICs of > 32 mg/L for penicillin G
      and imipenem, and MICs of > 256 mg/L for ampicillin, cefalotin and ceftriaxone.
      The organisms were resistant to nalidixic acid and vancomycin (MIC > 256 mg/L),
      but susceptible to tetracycline (MICs < 0.016-0.5 mg/L) and doxycycline (MICs <
      0.016-1 mg/L). The MIC of gentamicin ranged from 1 mg/L (P. limnophilus) to > 256
      mg/L (B. marina and P. brasiliensis); the MIC of erythromycin ranged from 0.032
      mg/L (P. limnophilus) to 2 mg/L (P. brasiliensis); the MIC for ciprofloxacin
      ranged from 0.008 mg/L (R. baltica) to > 32 mg/L (P. brasiliensis); and the MIC
      for colistin ranged from 0.125 mg/L (P. limnophilus) to 96 mg/L (B. marina).
      CONCLUSIONS: In addition to shedding new light on the biology of Planctomycetes
      organisms, these data could be used for the further phenotypic characterization
      of Planctomycetes organisms, and for the optimization of culture media for the
      primary isolation and growth of Planctomycetes organisms from contaminated
      specimens.

PMID- 20699246
TI  - In situ identification of follicles in ovarian cortex as a tool for quantifying
      follicle density, viability and developmental potential in strategies to preserve
      female fertility.
AB  - BACKGROUND: Ovarian tissue cryopreservation, in combination with
      autotransplantation or long-term culture, has been proposed as a means of
      fertility preservation. However follicle density within ovarian cortex has a
      profound impact on the success of in vivo and in vitro systems designed to
      support follicle growth and restore fertility. The objective of this study was to
      investigate the dye neutral red (NR) as a tool to quantify follicle density in
      situ, without compromising follicle viability and developmental potential.
      METHODS: In the first experimental series thin slices of cryopreserved and fresh
      ovine cortical tissue were incubated in 50 MUg/ml NR and assessed for the
      presence of red colouration. Slices were then used for follicular structure
      isolation and viability evaluation using 5-(and 6)-carboxyfluoresceindiacetate
      succinimidylester (CFDA-SE), or prepared histologically for follicle counting or
      evaluation of apoptosis via terminal deoxynucleotidyl transferase-mediated
      deoxyuridine triphosphate nick end labelling (TUNEL). An additional subset of
      slices were cultured for 8 days, followed by re-evaluation of follicle viability.
      NR staining was further assessed in a pilot study using thin slices of
      cryopreserved human ovarian tissue donated by 17 patients undergoing laparoscopic
      sterilisation or elective Caesarean section. RESULTS: In both ovine and human
      ovarian cortex NR concentrated in follicular structures within weakly stained
      stroma. NR colouration was observed in 41.7 +/- 4.6% of cryopreserved and 49.3 +/
      6.5% of the fresh ovine tissue slices, and NR staining was consistently
      predictive of the presence of follicles. Non-stained ovine slices contained
      highly apoptotic follicles, while lower levels of apoptosis were observed in NR
      positive slices, indicating preferential detection of viable follicles by NR.
      Following culture the majority of ovine slices re-stained with NR, no significant
      increases in the levels of apoptosis were observed and 94.6 +/- 3.1% of follicles
      were viable by CFDA-SE. In the human study, NR identified follicles in 19.3 +/-
      3.7% of tissue slices, and follicle density tended to decrease with advancing
      patient age. CONCLUSIONS: NR predicts viable follicle density in situ in slices
      of ovine and human ovarian cortex. Furthermore incubation of tissue in NR prior
      to culture does not compromise subsequent follicle survival in vitro, indicating
      the potential suitability of this approach in fertility preservation regimes.

PMID- 20699247
TI  - Inter-comparison of safety culture within selected practices in Ghana utilising
      ionising radiation.
AB  - The safety culture of selected practices and facilities in Ghana utilising
      radiation sources or radiation emitting devices has been assessed using a
      performance indicator, which provided status information on management and
      operating staff commitment to safety. The questionnaire was based on the
      following broad areas: general safety considerations, safety policy at the
      facility level, safety practices at the facility level, definition of
      responsibility, staff training, safety of the physical structure of the facility
      and the emergency plans. The analysis showed that the percentage levels of
      commitment to safety for the respective practices are as follows: conventional
      radiography, 23.3-90.0%; research reactor, 73.3%; gamma irradiation facility,
      53.3%; radiotherapy, 76.7%; X-ray scanner, 80.0%; gamma scanner, 76.7%;
      industrial radiography 86.7% and nuclear density practice, 78%. None of the
      practices or facilities was able to satisfy all the requirements that will ensure
      a 100% level of safety culture.

PMID- 20699248
TI  - Estimate of organ radiation absorbed doses in clinical CT using the radiation
      treatment planning system.
AB  - Organ absorbed doses in computed tomography (CT) scans can be measured with
      anatomical phantoms but not inside the human body. In this study, a
      straightforward method was investigated to estimate organ doses in clinical CT
      using the radiation treatment planning system (RTPS) and compared them with
      experimental results of photoluminescence dosemeters (PLD). In a heterogeneous
      phantom, the average difference between PLD and RTPS values were -5.0% for the
      body and 7.1% for the lung. Using CT data, organ doses in 30 clinical cases were
      then calculated. There was a significant inverse correlation between the
      calculated values of organ doses and body mass index (BMI, correlation
      coefficients (r) = -0.69 (whole body), -0.80 (right lung), -0.81 (left lung), 
      0.76 (spinal cord), -0.74 (vertebra bone), -0.74 (heart), and -0.79 (oesophagus),
      all p < 0.01). An RTPS can be a simple and useful tool for estimating equivalent
      doses inside the human body, during whole-body CT scans.

PMID- 20699249
TI  - Lycopene induces cell growth inhibition by altering mevalonate pathway and Ras
      signaling in cancer cell lines.
AB  - Several evidences suggest that cancer cells have abnormal cholesterol
      biosynthetic pathways and prenylation of small guanosine triphosphatase proteins.
      Tomato lycopene has been suggested to have beneficial effects against certain
      types of cancer, including that of prostate, although the exact molecular
      mechanism(s) is unknown. We tested the hypothesis that lycopene may exert its
      antitumor effects through changes in mevalonate pathway and in Ras activation.
      Incubation of the Ras-activated prostatic carcinoma LNCaP cells with a 24 h
      lycopene treatment (2.5-10 MUM) dose dependently reduced intracellular total
      cholesterol by decreasing 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA)
      reductase expression and by inactivating Ras, as evidenced by its translocation
      from cell membranes to cytosol. Concomitantly, lycopene reduced the Ras-dependent
      activation of nuclear factor-kappaB (NF-kappaB). Such a reduction was parallel to
      an inhibition of reactive oxygen species production and to a decrease in the
      phosphorylation ofc-jun N-terminal kinase, extracellular signal-regulated kinase
      1/2 and p38. These effects were also accompanied by an arrest of cell cycle
      progression and by apoptosis induction, as evidenced by a decrease in cyclin D1
      and phospho-AKT levels and by an increase in p21, p27 and p53 levels and in
      Bax:Bcl-2 ratio. The addition of mevalonate prevented the growth-inhibitory
      effects of lycopene as well as its increase in Ras cytoplasmatic accumulation and
      the subsequent changes in NF-kappaB. The ability of lycopene in inhibiting HMG
      CoA reductase expression and cell growth and in inactivating Ras was also found
      in prostate PC-3, colon HCT-116 and HT-29 and lung BEN cancer cells. These
      findings provide a novel mechanistic insight into the growth-inhibitory effects
      of lycopene in cancer.

PMID- 20699250
TI  - A rare and undesirable complication of heparin-induced thrombocytopenia: acute
      massive pulmonary embolism.
AB  - A 69-year-old woman presented to the emergency department with sudden onset of
      dyspnea. She reported bilateral total knee surgery 12 days prior for
      gonarthrosis. The patient was recommended low-molecular-weight heparin (LMWH) 0.4
      cc (4 milliliter) twice a day. On evaluation, severe thrombocytopenia was
      detected. An echocardiogram was performed because of her dyspnea, which revealed
      right ventricular dilatation and hypokinesis. Due to suspicion of a pulmonary
      embolism (PE), a pulmonary computed tomography (CT) was performed, which revealed
      bilateral massive PE. This event occurred while the patient was receiving LMWH
      for prophylaxis of PE. Due to the presence of severe thrombocytopenia,
      fondaparinux and immunoglobulin were initiated. Her platelet levels improved
      significantly and she was discharged on warfarin.

PMID- 20699251
TI  - Hyperhomocysteinemia prevalence among patients with venous thromboembolism.
AB  - The aim of this study is to evaluate the plasma total homocysteine level in
      patients with venous thromboembolism (VTE) and to investigate the effect of
      different risk factors on plasma levels. Ninety-three-patients with VTE and 37
      control participants diagnosed with other than VTE were included in the study.
      Plasma homocysteine levels and the factors affecting plasma homocysteine levels
      were evaluated. Plasma homocysteine level was higher among patients with VTE
      compared to the controls independent from vitamin B12 and folate levels. The
      prevalence of hyperhomocysteinemia in VTE was 63%. Plasma homocysteine level was
      higher in patients with PE than deep venous thrombosis (DVT; 23 +/- 13.7 vs 16 +/
      5.8 MUmol/L, P = .018). With regression analysis hyperhomocysteinemia was found
      to be associated with a 4.8-fold increased risk of VTE. Hyperhomocysteinemia is a
      common and possibly modifiable risk factor that should be considered when
      screening patients with VTE. Secondary causes of hyperhomocysteinemia especially
      vitamin B12 deficiency should be monitored in patients with VTE to prevent
      recurrences.

PMID- 20699252
TI  - Local anesthetics inhibit tissue factor expression in activated monocytes via
      inhibition of tissue factor mRNA synthesis.
AB  - Local anesthetics have been reported to have anticoagulant properties, but the
      mechanisms responsible for this action are poorly understood. Here, we evaluated
      the in vitro effects of 3 local anesthetics--lidocaine, ropivacaine, and
      bupivacaine--on the tissue factor expression by monocytes. Monocytes from
      peripheral blood were stimulated with lipopolysaccharide (LPS) in the presence or
      absence of local anesthetics. All 3 local anesthetics inhibited the expression of
      tissue factor antigen and tissue factor activity in LPS-stimulated monocytes in a
      dose- and time-dependent manner and reduced tissue factor messenger RNA (mRNA)
      expression in endothelial cells and a monocytic cell line. None of the 3 drugs
      induced apoptosis or affected the viability of monocytes. Our findings that local
      anesthetics inhibited the tissue factor induction in activated monocytes by
      inhibiting tissue factor mRNA level may demonstrate the feasibility of using
      local anesthetics in hypercoagulable and inflammatory conditions.

PMID- 20699253
TI  - The value of serum procalcitonin in differential diagnosis of pulmonary embolism
      and community-acquired pneumonia.
AB  - Presence of high fever may cause confusion in differential diagnosis of pulmonary
      embolism (PE) versus pneumonia. The aim of this study is to investigate the
      diagnostic value of serum procalcitonin (PCT) in differential diagnosis of PE and
      community-acquired pneumonia (CAP). A total of 24 patients with proven PE and 22
      patients with CAP were included in the study. The study population was subdivided
      as PE patients with fever (group 1, n = 8) and without fever (group 2, n = 16);
      and CAP (group 3, n = 22). Serum PCT and systemic inflammatory markers were
      measured at the initial diagnosis and the third day of the treatment. The
      relation of PCT level with the other systemic inflammatory markers was
      investigated in each measurement point. The initial mean serum PCT level in group
      3 (2.24 +/- 0.99 ng/mL) was statistically higher than group 1 (0.48 +/- 0.77
      ng/mL) and group 2 (0.14 +/- 0.17 ng/mL; P = .000, .000, respectively).
      Procalcitonin level at the initial (2.24 +/- 0.99 ng/mL) and the third day of
      treatment (0.92 +/- 0.62 ng/mL) in group 3 showed a statistically significant
      reduction (P = .000). There were no statistically significant reduction in PCT
      levels by anticoagulation in groups 1 and 2 (P = .262, .119, respectively). Other
      systemic inflammatory markers including interleukin 6 (IL-6), C-reactive protein
      (CRP), and tumor necrosis factor alpha (TNF-alpha) levels statistically
      significantly decreased with anticoagulant and antimicrobial therapy. This study
      suggested that serum PCT level may be valuable for differentiating PE patients
      with or without fever from patients with CAP.

PMID- 20699254
TI  - Acquired platelet dysfunction in 109 patients from a tertiary care referral
      hospital.
AB  - BACKGROUND: Acquired platelet function defects (PFDs) remain poorly
      characterized, underrecognized, and therefore understudied. PATIENTS/METHODS:
      Clinical and laboratory records of 109 patients with acquired PFDs diagnosed over
      5 years were analyzed. Screening studies (platelet count, prothrombin time,
      activated partial thromboplastin time, and thrombin time), template bleeding
      time, platelet factor 3 (PF-3) availability test, light-transmission
      aggregometry, and further testing as indicated were performed. RESULTS: 64
      patients had mild and 26 had major bleeding. In all, 15 were referred for
      preoperative testing, whereas 4 had thrombotic events. Causes and associations of
      PFDs were drug-induced (34), idiopathic (34), hematopoietic neoplasms (15;
      myeloma 4, Waldenstrom macroglobulinemia 2, chronic myeloid leukemia 4, essential
      thrombocythaemia 3, and primary myelofibrosis and chronic lymphocytic leukemia 1
      each), chronic liver disease (4), postcardiac surgery (2), uremia (2), and
      thalassemia major (7). Miscellaneous disorders comprised the rest. CONCLUSIONS:
      Acquired PFDs span a wide range of disease settings. Systematic, sequential
      laboratory testing identifies patterns of dysfunction, excludes inherited
      disorders, and streamlines management.

PMID- 20699255
TI  - State-of-the-art review: Hemostats, sealants, and adhesives II: Update as well as
      how and when to use the components of the surgical toolbox.
AB  - The goal of this submission is to describe how and when to best use hemostats,
      sealants, and adhesives as well as to compare their characteristics and to update
      the surgical toolbox with respect to any new products approved by the Food and
      Drug Administration (FDA) as of this date (November 2009). The materials will be
      presented in 3 major groups each containing specific categories: (1) hemostats;
      mechanical, active, flowable, and fibrin sealant, (2) sealants; fibrin sealant,
      polyethylene glycol polymer, and albumin and glutaraldehyde, (3) adhesives;
      cyanoacrylate, albumin and glutaraldehyde, and fibrin sealant. The categories
      will be used for comparisons based on safety, efficacy, usability, and cost.
      Recommendations with respect to how and when to best use these materials will be
      presented. A review of the recent literature is also provided with respect to the
      most recent uses of these materials in specific surgical specialties.

PMID- 20699256
TI  - Inflammatory and prothrombotic activation with conserved endothelial function in
      patients with chronic, asymptomatic Chagas disease.
AB  - Previously, our group showed a prothrombotic state in asymptomatic patients with
      chronic Chagas disease. The current paper studies the inflammatory status and
      endothelial function in these patients. METHODS: In 40 patients and 40 healthy
      volunteers, we evaluated prothrombotic state, blood parasitemia (molecular
      biology: polymerized chain reaction [PCR]-amplification), tissue factor pathway
      inhibitor antibodies (aTFPI), interleukin 6 (IL-6), and vascular cell adhesion
      molecule-1 (VCAM-1). Endothelial function was determined by reactive hyperemia
      (pulse plethysmography). RESULTS: In patients, prothrombin fragment 1 + 2, d
      dimer, PAI-1, and fibrinogen were higher. Amplification of 121/122 primers
      (Trypanosoma cruzi) was positive in 45% of the patients. Patients presented
      higher values of aTFPI- immunoglobulin G (IgG; P < .05), aTFPI-IgM (P < .001), IL
      6 (P = .004), and VCAM-1 (P = .00001). In both groups, endothelial function was
      preserved. CONCLUSIONS: We found that asymptomatic patients with chronic Chagas
      disease presented a prothrombotic/inflammatory status. The fact that endothelial
      function is still preserved suggests that prothrombosis and inflammation are
      primarily implicated in the beginning of cardiovascular damage.

PMID- 20699257
TI  - Venous gangrene a rare but dreadful complication of deep venous thrombosis.
AB  - Venous gangrene is a rare complication of deep venous thrombosis. It is certain
      from review of literature that there is a significant causative relationship
      between malignant disease and venous gangrene. Data from the National hospital
      discharge survey from 1979 to 2006 showed that 0.43% of patients with deep venous
      thrombosis had gangrene, while 1.39% patients with gangrene had deep venous
      thrombosis. Toes and fingers are frequent site of venous gangrene in patients
      with massive deep venous thrombosis, as evident by review of literature. A
      possible explanation for this occurrence can be the fact that because of the
      scarcity of subcutaneous fat and the small spaces of fingers and toes, massive
      edema can generate large compressive forces; these forces may have a compressive
      effect on the arterioles, which may contribute to the development of venous
      gangrene. Lower extremities develop venous gangrene more commonly than upper
      extremities. The condition has an extremely high rate of mortality either from
      pulmonary embolism or from the serious underlying disease, such as neoplasms.

PMID- 20699258
TI  - Low-molecular-weight heparin versus unfractionated heparin for prophylaxis of
      venous thromboembolism in medicine patients--a pharmacoeconomic analysis.
AB  - BACKGROUND: Prevention of in-hospital venous thromboembolism (VTE) is identified
      internationally as a priority to improve patient safety. Advocated alternatives
      include low-dose unfractionated heparin (UFH) or low-molecular-weight heparin
      (LMWH). Although LMWHs are as effective as UFH, less frequent administration and
      potentially safer adverse effect profile associated with LMWHs might off-set
      greater drug acquisition costs. The objective of this study was to determine the
      most cost-effective thromboprophylaxis strategy for hospitalized medicine
      patients and specific subgroups in Canada. METHODS: A decision-analytic model
      assessed costs and outcomes of LMWH compared to UFH for thromboprophylaxis in at
      risk hospitalized medicine patients from an institutional perspective. The
      outcome of interest was the incremental cost-effectiveness ratio (ICER) for
      preventing deep vein thrombosis (DVT) and combined untoward events (pulmonary
      embolism [PE], major bleed, and death). The time horizon of the model was the
      hospital stay. RESULTS: In the base-case analysis, LMWH thromboprophylaxis
      resulted in higher costs ($7.40), but 3.6 and 1.1 fewer DVT and untoward events
      per 1000 patients, respectively, with associated ICERs of $2042 and $6832.
      Results remained predominantly stable when alternative assumptions were evaluated
      in the sensitivity analysis. Low-molecular-weight heparin had the most favorable
      economic profile in patients with a history of DVT. In the probabilistic
      sensitivity analysis, in 33% of simulations LMWH was less costly and more
      effective, whereas the reverse was true for UFH only in 13% of simulations.
      CONCLUSIONS: Low-molecular-weight heparin administration is a cost-effective
      alternative for thromboprophylaxis strategy in Canadian hospitalized medicine
      patients.

PMID- 20699259
TI  - Effects of pegylated interferon alpha on fibrinolytic parameters in patients with
      chronic hepatitis C.
AB  - Interferon (IFN) interacts with endothelial cells and modulates the functions of
      these cells. In our study, we aimed to determine the effects of treatment with
      pegylated IFN-alpha (peg-IFN-alpha) on fibrinolytic parameters in patients with
      chronic hepatitis C. Fifteen patients with chronic hepatitis C were treated with
      peg-IFN-alpha once per week plus daily oral ribavirin. Euglobulin lysis time
      (ELT), plasma levels of D-dimer, tissue-type plasminogen activator (t-PA),
      plasminogen activator inhibitor 1 (PAI-1), and thrombin activatable fibrinolysis
      inhibitor (TAFI) were determined before treatment, 2 weeks, 1 month, and 3 months
      after the initiation of the treatment. Plasma levels of t-PA increased
      significantly 1 month and 3 months after the treatment (P < .05). The PAI-1 and
      TAFI levels in 2 weeks, 1 month and 3 months after treatment were not
      statistically different as compared with pretreatment levels (P > .05) No
      significant difference in plasma D-dimer levels was observed during peg-IFN-alpha
      treatment (P > .05). There was a significant decrease in ELT 1 month and 3 months
      after the treatment (P < .05). Our results indicated that treatment with peg-IFN
      alpha may be associated with enhanced fibrinolysis.

PMID- 20699260
TI  - Cross-reactivity of rabbit anti-bovine prothrombin/thrombin IgGs with bovine
      factor V/Va-related antigens.
AB  - The purpose of this study was to determine whether rabbit anti-bovine
      prothrombin/thrombin immunoglobulin Gs (IgGs) would cross-react with bovine
      factor V/Va-related antigens. Bovine prothrombin, crude thrombin, as well as 2
      purified versions of thrombin, that is, thrombin 4A (the previous version of
      Thrombin-JMI marketed prior to 2008) and 4B (the currently marketed version of
      Thrombin-JMI), were administrated to individual groups of rabbits on days 0, 21,
      42, 91, 123, and 151 using standard immunologic methods. Blood was drawn from
      each rabbit on days 30, 50, 105, 137, and 165 and the pooled antisera from
      individual groups were purified to obtain the IgGs using protein G affinity
      columns. By probing bovine factor V/Va samples, the possible cross-reactivity of
      each IgG collected at different time points (from day 30 to day 165) was explored
      using Western blotting techniques. The results indicated that rabbit anti-bovine
      prothrombin and crude thrombin IgGs could cross-react strongly with bovine factor
      V/Va in an immunization time-dependent manner. However, antibodies generated in
      thrombin 4A-treated rabbits presented much weaker cross-reactivity with bovine
      factor V/Va. Furthermore, no cross-reactivity with bovine factor V/Va-related
      antigens was observed when the anti-bovine thrombin 4B IgG collected at any time
      point was used. The results suggest that thrombin 4B preparation contains the
      least bovine factor V/Va contaminants among the bovine prothrombin/thrombin
      preparations studied and the amount of bovine factor V/Va contaminants in bovine
      thrombin 4B is too small to elicit the generation of antibodies against bovine
      factor V/Va in rabbits.

PMID- 20699261
TI  - Prothrombotic profile in children with peripheral gangrene: a single center
      experience.
AB  - Peripheral gangrene is rare in children. Protein C, protein S, and antithrombin
      deficiency, positivity for anticardiolipin antibodies or lupus anticoagulant and
      factor V Leiden mutation are important causes of thrombosis in the venous system.
      There is paucity of literature on the contribution of these factors in children
      with peripheral gangrene. We evaluated the role of aforementioned factors in
      children with peripheral gangrene. Protein S deficiency was seen in one case and
      another was transiently positive for lupus anticoagulant. None of the 11 age- and
      sex-matched normal controls had protein C, protein S, or antithrombin deficiency.
      Our results indicate that deficiency of protein C, protein S, and antithrombin,
      and positivity for anticardiolipin antibodies, lupus anticoagulant, and factor V
      Leiden are uncommon causes of peripheral gangrene in children in north-western
      India. Fibrinolytic and antiplatelet parameters were not tested. Testing for
      these may yield further clues to the etiology of this condition.

PMID- 20699262
TI  - Effect of stimulation of the laryngopharynx with water and salt solutions on
      voluntary swallowing in humans: characteristics of water receptors in the
      laryngopharyngeal mucosa.
AB  - Stimulation of water receptors in the laryngopharynx (LP) with water facilitates
      voluntary swallowing in humans. Based on measures of swallowing intervals (SIs)
      in repetitive swallowing, we investigated characteristics of laryngopharyngeal
      water receptors in humans. Healthy adult volunteers were instructed to perform
      repetitive swallowing as quickly as possible during infusion of a solution into
      the LP. Infusion of water shortened SI, suggesting that water excites water
      receptors. Infusion of 0.3 M NaCl solution prolonged SI, suggesting that the NaCl
      solution inhibits activity of water receptors. SI increased with increasing
      concentration of NaCl. Anion or cation substitutions indicated that excitation of
      water receptors is due to absence or reduced concentration of Cl(-). With
      diminution of peripheral inputs, cortical inputs would play a dominant role in
      voluntary swallowing. With infusion of a nonstimulating solution (0.3 M NaCl at
      0.2 mL/min), SI varied greatly from subject to subject, suggesting that the
      ability of central regulation of swallowing to initiate repetitive voluntary
      swallowing varies among subjects. Facilitation of swallowing by chemosensory
      inputs from water receptors appeared strongly in subjects with longer SI with
      infusion of the nonstimulating solution. It appears that chemosensory activation
      compensates for the difficulty in initiating swallowing via the central neural
      mechanism.

PMID- 20699263
TI  - Is there an association between low-to-moderate alcohol consumption and risk of
      cognitive decline?
AB  - The authors evaluated the association of low-to-moderate alcohol consumption with
      risk of cognitive decline in a census-based cohort study of men and women aged
      >=55 years conducted in Zaragoza, Spain (1994-1999). Participants free of
      dementia at baseline (N = 3,888) were examined after 2.5 and 4.5 years of follow
      up. Information on alcohol intake was collected with the EURODEM Risk Factors
      Questionnaire and the History and Aetiology Schedule. The study endpoint was
      severe cognitive decline, defined as loss of >=1 point/year on the Mini-Mental
      State Examination or a diagnosis of incident dementia (Diagnostic and Statistical
      Manual of Mental Disorders: DSM-IV, Text Revision criteria). Compared with those
      for abstainers, the multivariate-adjusted odds ratios for severe cognitive
      decline for male drinkers of <12 g alcohol/day, drinkers of 12-24 g alcohol/day,
      and former drinkers were 0.61 (95% confidence interval (CI): 0.31, 1.20), 1.19
      (95% CI: 0.61, 2.32), and 1.03 (95% CI: 0.59, 1.82), respectively. The
      corresponding odds ratios for women were 0.88 (95% CI: 0.45, 1.72), 2.38 (95% CI:
      0.98, 5.77), and 1.03 (95% CI: 0.48, 2.23). This study did not support the
      hypothesis that low-to-moderate alcohol consumption prevents cognitive decline.
      The inverse association between low-to-moderate alcohol intake and cognitive
      decline observed in other studies may have been due to inclusion of former
      drinkers in the abstainers reference category.

PMID- 20699268
TI  - COI1, a jasmonate receptor, is involved in ethylene-induced inhibition of
      Arabidopsis root growth in the light.
AB  - Plant response to stress is orchestrated by hormone signalling pathways including
      those activated by jasmonates (JAs) and by ethylene, both of which stunt root
      growth. COI1 is a JA receptor and is required for the known responses to this
      hormone. It was observed that the coi1 mutant, which is largely unresponsive to
      growth inhibition by JAs, was also partially unresponsive to growth inhibition by
      ethylene and by its immediate precursor, 1-aminocyclopropane-1-carboxylic acid
      (ACC), in the light but not in the dark. Although COI1 was required for this
      response to ACC, other components of the JA signal perception pathway were not.
      Mutants selected for insensitivity to ethylene, including etr1, ein2, and ein3,
      showed greater ACC-induced root growth inhibition in the light than in the dark.
      However, the double mutants etr1;coi1, ein2;coi1, and ein3;coi1, and coi1
      seedlings treated with silver ions to block the ethylene receptors showed almost
      complete unresponsiveness to ACC-induced root growth inhibition in the light. The
      light requirement for the COI1-mediated growth inhibition by ACC was for long
      photoperiods, and the ACC response was not abolished by mutations in the known
      photoreceptors. The complementation assay indicated that SCF complex assembly was
      not required for COI1 function in the ACC response, in contrast to the JA
      response. It is concluded that COI1 is required for the light-dependent, JA
      independent, root growth inhibition by ethylene.

PMID- 20699269
TI  - Identification of rare alleles and their carriers using compressed se(que)nsing.
AB  - Identification of rare variants by resequencing is important both for detecting
      novel variations and for screening individuals for known disease alleles. New
      technologies enable low-cost resequencing of target regions, although it is still
      prohibitive to test more than a few individuals. We propose a novel pooling
      design that enables the recovery of novel or known rare alleles and their
      carriers in groups of individuals. The method is based on a Compressed Sensing
      (CS) approach, which is general, simple and efficient. CS allows the use of
      generic algorithmic tools for simultaneous identification of multiple variants
      and their carriers. We model the experimental procedure and show via computer
      simulations that it enables the recovery of rare alleles and their carriers in
      larger groups than were possible before. Our approach can also be combined with
      barcoding techniques to provide a feasible solution based on current resequencing
      costs. For example, when targeting a small enough genomic region (~100 bp) and
      using only ~10 sequencing lanes and ~10 distinct barcodes per lane, one recovers
      the identity of 4 rare allele carriers out of a population of over 4000
      individuals. We demonstrate the performance of our approach over several publicly
      available experimental data sets.

PMID- 20699270
TI  - Critical lysine residues within the overlooked N-terminal domain of human APE1
      regulate its biological functions.
AB  - Apurinic/apyrimidinic endonuclease 1 (APE1), an essential protein in mammals, is
      involved in base excision DNA repair (BER) and in regulation of gene expression,
      acting as a redox co-activator of several transcription factors. Recent findings
      highlight a novel role for APE1 in RNA metabolism, which is modulated by
      nucleophosmin (NPM1). The results reported in this article show that five lysine
      residues (K24, K25, K27, K31 and K32), located in the APE1 N-terminal
      unstructured domain, are involved in the interaction of APE1 with both RNA and
      NPM1, thus supporting a competitive binding mechanism. Data from kinetic
      experiments demonstrate that the APE1 N-terminal domain also serves as a device
      for fine regulation of protein catalytic activity on abasic DNA. Interestingly,
      some of these critical lysine residues undergo acetylation in vivo. These results
      suggest that protein-protein interactions and/or post-translational modifications
      involving APE1 N-terminal domain may play important in vivo roles, in better
      coordinating and fine-tuning protein BER activity and function on RNA metabolism.

PMID- 20699271
TI  - Heterogeneous ribonucleoprotein C displays a repressor activity mediated by T
      cell intracellular antigen-1-related/like protein to modulate Fas exon 6 splicing
      through a mechanism involving Hu antigen R.
AB  - T-cell intracellular antigen (TIA)-proteins are known regulators of alternative
      pre-mRNA splicing. In this study, pull-down experiments and mass spectrometry
      indicate that TIAR/TIAL1 and hnRNP C1/C2 are associated in HeLa nuclear extracts.
      Co-immunoprecipitation and GST-pull-down assays confirmed this interaction.
      Interestingly, binding requires the glutamine-rich (Q-rich) C-terminal domain of
      TIAR and the leucine-rich plus acidic residues-rich C-terminal domains of hnRNP
      C1/C2. This interaction also occurs in an RNA-dependent manner. Recombinant GFP
      TIAR and RFP-hnRNP C1 proteins display partial nuclear co-localization when
      overexpressed in HeLa cells, and this requires the Q-rich domain of TIAR. hnRNP
      C1 overexpression in the presence of rate-limiting amounts of TIAR in HeLa and
      HEK293 cells affects alternative splicing of Fas and FGFR2 minigenes, promoting
      Fas exon 6 and FGFR2 exon K-SAM skipping, respectively. The repressor activity of
      hnRNP C1 on Fas exon 6 splicing is mediated by Hu antigen R (HuR). Experiments
      involving tethering approaches showed that the repressor capacity of hnRNP C1 is
      associated with an exonic splicing silencer in Fas exon 6. This effect was
      reversed by splice-site strengthening and is linked to its basic leucine zipper
      like motif. These results suggest that hnRNP C1/C2 acts as a bridge between HuR
      and TIAR to modulate alternative Fas splicing.

PMID- 20699272
TI  - Single molecule linear analysis of DNA in nano-channel labeled with sequence
      specific fluorescent probes.
AB  - An array of nano-channels was fabricated from silicon based semiconductor
      materials to stretch long, native dsDNA. Here we present a labeling scheme in
      which it is possible to identify the location of specific sequences along the
      stretched DNA molecules. The scheme proceeds by first using the strand
      displacement activity of the Vent (exo-) polymerase to generate single strand
      flaps on nicked dsDNA. These single strand flaps are hybridized with sequence
      specific fluorophore-labeled probes. Subsequent imaging of the DNA molecules
      inside a nano-channel array device allows for quantitative identification of the
      location of probes. The highly efficient DNA hybridization on the ss-DNA flaps is
      an excellent method to identify the sequence motifs of dsDNA as it gives us
      unique ability to control the length of the probe sequence and thus the frequency
      of hybridization sites on the DNA. We have also shown that this technique can be
      extended to a multi color labeling scheme by using different dye labeled probes
      or by combining with a DNA- polymerase-mediated incorporation of fluorophore
      labeled nucleotides on nicking sites. Thus this labeling chemistry in conjunction
      with the nano-channel platform can be a powerful tool to solve complex structural
      variations in DNA which is of importance for both research and clinical
      diagnostics of genetic diseases.

PMID- 20699273
TI  - A link between nuclear RNA surveillance, the human exosome and RNA polymerase II
      transcriptional termination.
AB  - In eukaryotes, the production of mature messenger RNA that exits the nucleus to
      be translated into protein in the cytoplasm requires precise and extensive
      modification of the nascent transcript. Any failure that compromises the
      integrity of an mRNA may cause its retention in the nucleus and trigger its
      degradation. Multiple studies indicate that mRNAs with processing defects
      accumulate in nuclear foci or 'dots' located near the site of transcription, but
      how exactly are defective RNAs recognized and tethered is still unknown. Here, we
      present evidence suggesting that unprocessed beta-globin transcripts render RNA
      polymerase II (Pol II) incompetent for termination and that this quality control
      process requires the integrity of the nuclear exosome. Our results show that
      unprocessed pre-mRNAs remain tethered to the DNA template in association with Pol
      II, in an Rrp6-dependent manner. This reveals an unprecedented link between
      nuclear RNA surveillance, the exosome and Pol II transcriptional termination.

PMID- 20699274
TI  - TAL nucleases (TALNs): hybrid proteins composed of TAL effectors and FokI DNA
      cleavage domain.
AB  - DNA double-strand breaks enhance homologous recombination in cells and have been
      exploited for targeted genome editing through use of engineered endonucleases.
      Here we report the creation and initial characterization of a group of rare
      cutting, site-specific DNA nucleases produced by fusion of the restriction enzyme
      FokI endonuclease domain (FN) with the high-specificity DNA-binding domains of
      AvrXa7 and PthXo1. AvrXa7 and PthXo1 are members of the transcription activator
      like (TAL) effector family whose central repeat units dictate target DNA
      recognition and can be modularly constructed to create novel DNA specificity. The
      hybrid FN-AvrXa7, AvrXa7-FN and PthXo1-FN proteins retain both recognition
      specificity for their target DNA (a 26 bp sequence for AvrXa7 and 24 bp for
      PthXo1) and the double-stranded DNA cleaving activity of FokI and, thus, are
      called TAL nucleases (TALNs). With all three TALNs, DNA is cleaved adjacent to
      the TAL-binding site under optimal conditions in vitro. When expressed in yeast,
      the TALNs promote DNA homologous recombination of a LacZ gene containing paired
      AvrXa7 or asymmetric AvrXa7/PthXo1 target sequences. Our results demonstrate the
      feasibility of creating a tool box of novel TALNs with potential for targeted
      genome modification in organisms lacking facile mechanisms for targeted gene
      knockout and homologous recombination.

PMID- 20699275
TI  - On the power and limits of evolutionary conservation--unraveling bacterial gene
      regulatory networks.
AB  - The National Center for Biotechnology Information (NCBI) recently announced '1000
      prokaryotic genomes are now completed and available in the Genome database'. The
      increasing trend will provide us with thousands of sequenced microbial organisms
      over the next years. However, this is only the first step in understanding how
      cells survive, reproduce and adapt their behavior while being exposed to changing
      environmental conditions. One major control mechanism is transcriptional gene
      regulation. Here, striking is the direct juxtaposition of the handful of
      bacterial model organisms to the 1000 prokaryotic genomes. Next-generation
      sequencing technologies will further widen this gap drastically. However, several
      computational approaches have proven to be helpful. The main idea is to use the
      known transcriptional regulatory network of reference organisms as template in
      order to unravel evolutionarily conserved gene regulations in newly sequenced
      species. This transfer essentially depends on the reliable identification of
      several types of conserved DNA sequences. We decompose this problem into three
      computational processes, review the state of the art and illustrate future
      perspectives.

PMID- 20699277
TI  - Posterior reversible encephalopathy syndrome in childhood cancer.
AB  - BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is characterized
      by seizures, headaches, altered mental status, cortical blindness and typical
      transient lesions on magnetic resonance imaging. PATIENTS AND METHODS: We
      describe seven childhood cancer patients with clinical and radiological symptoms
      of PRES, and reviewed all well-documented PRES cases reported during childhood
      cancer treatment. RESULTS: Fifty-six children with PRES, including our 7 cases,
      were identified in the literature. Mean age at onset was 9 (range: 2-17) years.
      Primary diagnoses were acute lymphoblastic leukemia (n = 31), acute myeloid
      leukemia (n = 5), non-Hodgkin lymphoma (n = 7) and solid tumors (n = 13). PRES
      patients presented with seizures (n = 50), altered mental status (n = 20), visual
      disturbances (n = 24) and/or headaches (n = 17). PRES was associated with
      hypertension in 49 patients. About 86% of the patients had both clinical and
      radiological reversible symptoms. Four patients developed epilepsy, in one
      patient ataxia remained and one patient had a persistent mydriasis. CONCLUSION:
      Although PRES has predominantly been described in leukemia patients, it occurs in
      children with solid tumors as well. Hypertension seems to be the most important
      trigger for the occurrence of PRES during childhood cancer treatment. Seizures
      are the most common accompanying sign. Symptoms and radiological findings
      normalize in ~90% of the cases, but in 10% neurological symptoms remain.

PMID- 20699278
TI  - Time trend in treatment-related deaths of patients with advanced non-small-cell
      lung cancer enrolled into phase III trials of systemic treatment.
AB  - PURPOSE: Despite recent improvements in supportive care, treatment-related death
      (TRD) remains a serious problem for lung cancer patients undergoing systemic
      chemotherapy. However, few studies have formally assessed possible changes in the
      TRD rate over the past two decades. PATIENTS AND METHODS: We searched phase III
      trials to address the role of systemic treatment of advanced non-small-cell lung
      cancer (NSCLC). Time trend was assessed using linear regression analysis.
      RESULTS: The overall incidence of TRD was calculated from 119 trials including
      263 chemotherapy arms (46 477 patients), with information about the causes of
      deaths available for 197 arms (75%, 30 147 patients). Cisplatin-based regimens
      were the most frequently investigated. The crude TRD rate in the overall cohort
      of 119 trials was 1.26% and has been notably consistent over the investigated
      time (P = 0.762). The most common cause of death was febrile neutropenia, with no
      significant change in its incidence over the years (P = 0.139). In contrast,
      deaths due to renal toxicity decreased significantly (P = 0.042), whereas deaths
      due to pulmonary disorder increased significantly (P = 0.007). Among the
      pharmacological agents investigated, docetaxel (Taxotere) and epidermal growth
      factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) were associated with
      relatively high rates of deaths from pulmonary disorders, but EGFR-TKIs were not
      associated with death from any other cause. CONCLUSIONS: Despite of potential
      confounders in our results, the overall TRD rate has remained low, but not
      negligible, in phase III trials for advanced NSCLC, over the past two decades.
      Notably, the incidence and pattern of TRD stratified by cause have changed
      considerably.

PMID- 20699276
TI  - Design of a minimal silencer for the silent mating-type locus HML of
      Saccharomyces cerevisiae.
AB  - The silent mating-type loci HML and HMR of Saccharomyces cerevisiae contain
      mating-type information that is permanently repressed. This silencing is mediated
      by flanking sequence elements, the E- and I-silencers. They contain combinations
      of binding sites for the proteins Rap1, Abf1 and Sum1 as well as for the origin
      recognition complex (ORC). Together, they recruit other silencing factors,
      foremost the repressive Sir2/Sir3/Sir4 complex, to establish heterochromatin-like
      structures at the HM loci. However, the HM silencers exhibit considerable
      functional redundancy, which has hampered the identification of further silencing
      factors. In this study, we constructed a synthetic HML-E silencer (HML-SS DeltaI)
      that lacked this redundancy. It consisted solely of Rap1 and ORC-binding sites
      and the D2 element, a Sum1-binding site. All three elements were crucial for
      minimal HML silencing, and mutations in these elements led to a loss of Sir3
      recruitment. The silencer was sensitive to a mutation in RAP1, rap1-12, but less
      sensitive to orc mutations or sum1Delta. Moreover, deletions of SIR1 and DOT1
      lead to complete derepression of the HML-SS DeltaI silencer. This fully
      functional, minimal HML-E silencer will therefore be useful to identify novel
      factors involved in HML silencing.

PMID- 20699279
TI  - Obesity and immune cells in Saudi females.
AB  - For the past two decades or more, obesity has been increasing in industrialized
      and affluent countries. This increase has been shown in children, adults and the
      elderly. The latest statistical studies in Saudi Arabia show that obesity is
      increasing, with obese Saudi women outnumbering obese Saudi males, and that these
      numbers are continuously rising. Obesity, which leads to many medical risks,
      affects the immune system in direct and indirect ways. In this study, the effect
      of obesity on the immune system of 119 Saudi female university students was
      investigated. Using a blood sample from each subject, the following immune
      related parameters were determined: total and differential white blood cell
      counts (WBCs), total lymphocyte and sub-lymphocyte cell counts. Two measures of
      body fat were used: the body mass index (BMI) and the waist-to-hip ratio (WHR) to
      correlate body weight to the other measured parameters. A significant correlation
      was present between BMI and WHR each with total white blood cells, neutrophils,
      and CD4 lymphocyte concentrations. Some other parameters were only affected by
      the increase in the BMI but not the WHR, such as platelets, while others were
      affected by the WHR only, such as total T-cells. On the other hand, there were no
      significant correlations between BMI or WHR and basophil, eosinophil, monocyte,
      CD8, B-cell, and NK-cell counts. The findings indicate that obesity might
      seriously affect the innate and adaptive immune systems.

PMID- 20699280
TI  - Regulation of colon cancer cell proliferation and migration by MD-2 activity.
AB  - Evidence suggests that signalling through lipopolysaccharide (LPS) has a
      significant role in the development of gastrointestinal malignancies. We
      previously demonstrated the critical role of myeloid differentiation (MD)-2, the
      essential co-receptor of LPS, for induction of cyclooxygenase (Cox)-2 in
      intestinal epithelial cells. Cyclooxigenase-2 was suggested to play a key role in
      colorectal cancer through the effects of prostaglandin (PG) E(2) generated. We,
      therefore, addressed the role of MD-2 in several parameters related to
      malignancy, namely cell proliferation and migration, using colon cancer cells (HT
      29). We found that overexpression of MD-2 confers a significantly greater
      proliferation and migration capacity to these cells. MD-2-dependent proliferation
      and migration appeared independent of Cox-2 activity but was reduced by
      endothelial growth factor receptor (EGFR) neutralizing antibodies as well as by
      pharmacological inhibition of EGFR tyrosine phosphorylation. We propose that MD-2
      overexpression contributes to tumour aggressiveness via a Cox-2-independent
      excessive EGFR signalling. Moreover, MD-2 expression levels were higher in tissue
      from patients with colorectal cancer as compared with paired control colorectal
      mucosa. Our data attest to a role of MD-2 activity in colon cancer epithelial
      cell proliferation and migration, which may be important in the general
      correlation between innate immune response, chronic inflammation, and cancer.

PMID- 20699281
TI  - MyD88-dependent pro-inflammatory cytokine response contributes to lethal toxicity
      of staphylococcal enterotoxin B in mice.
AB  - An elevated pro-inflammatory cytokine response is the primary cause of death by
      toxic shock after exposure to staphylococcal enterotoxin B (SEB). Identifying an
      intracellular signal mediator that predominantly controls the pro-inflammatory
      response is important for developing a therapeutic strategy. We examined the role
      of the signaling adaptor MyD88 in cell culture and in a mouse model of toxic
      shock. Our results indicated that elevated tumor necrosis factor-alpha,
      interferon-gamma, interleukin (IL)-1alpha/beta and IL-6 production from mouse
      spleen cells treated with SEB alone or in combination with lipopolysaccharide
      (LPS) was regulated by MyD88. Elevated levels of MyD88 protein in spleen cells,
      as well as in CD11c(+) or Mac3(+) cells, and activation of nuclear factor-kappaB
      in spleen cells were observed in mice treated with SEB. An SEB-dose dependent
      lethality was observed in LPS-potentiated and in D-galactosamine-sensitized mice.
      D-Galactosamine treatment of spleen cells had no effect in cytokine induction but
      rather increased the sensitivity to toxic shock in mice. Our results demonstrated
      an impaired pro-inflammatory cytokine production by spleen cells of MyD88(-/-)
      mice in response to SEB or SEB plus LPS. Most importantly, MyD88(-/-) mice were
      resistant to SEB-induced death. These results demonstrate that MyD88-dependent
      pro-inflammatory signaling is responsible for SEB intoxication. In addition, our
      studies also demonstrated that LPS potentiation, in comparison to D-galactosamine
      sensitization, contributes to a stronger SEB-induced lethality. This is due to
      the pro-inflammatory cytokine response elicited by MyD88 after exposure to SEB
      and LPS. These findings offer an important insight upon SEB intoxication and
      subsequent therapy targeting MyD88.

PMID- 20699282
TI  - The many faces of the YopM effector from plague causative bacterium Yersinia
      pestis and its implications for host immune modulation.
AB  - The Yersinia outer protein (Yop) M effector from the Yersinia pestis bacterium is
      well-known for being a critical virulence determinant; however, structural
      insight vis-a-vis its role in Y. pestis pathogenesis has been elusive. Here, we
      investigate the intact sequence of the YopM protein through our recently
      developed fold identification and homology modeling tools, and analyze the immune
      modulatory potential of its constituent domains. We identify a putative novel E3
      ligase (NEL) domain towards the C-terminal tail of YopM and characterize its
      active site, to show that YopM could function as an autoregulated bacterial type
      E3 ubiquitin ligase. We further identify unreported NEL domains in several other
      bacteria and note remarkable similarity in sequence, structure, surface, and
      electrostatics for the family of NEL-containing bacterial effectors that suggests
      conserved function and potentially similar host targets for these proteins. Based
      on these observations and recent empirical evidence for degradation of the human
      proteins HLA-DR, thioredoxin, and NEMO/IKKgamma by other members of the NEL
      containing bacterial family, we discuss the potential for YopM to modulate a wide
      spectrum of immune signal transduction pathways. The key immune modulatory
      effects highlighted are suppression of MHC class II antigen presentation,
      dampening of nuclear factor (NF)-kappaB mediated inflammatory response, and
      intonation of mitogen-activated protein kinase (MAPK) signaling. Additionally,
      our analysis of the modeled YopM LRR domain reveals structural features akin to
      the Toll-like receptor 4 (TLR4) LRR motif. We propose that YopM LRR could be a
      'molecular mimic' of TLR4 LRR, permitting reduced immunogenicity and potentially
      mitigating bacterial lipopolysaccharide surveillance of the innate immune system.
      Our identification and characterization of the YopM NEL domain, taken together
      with our analysis of the YopM LRR domain, provides plausible insight into
      subversion of host immunity by Y. pestis YopM and perhaps could set the stage for
      design of new therapeutic opportunities.

PMID- 20699283
TI  - Identification of components of grape powder with anti-apoptotic effects.
AB  - This study is to investigate the mechanism underlying the anti-apoptotic effects
      of freeze-dried grape powder (FDGP) and identify the polyphenolic compounds
      involved. We examined apoptotic signaling pathways affected by FDGP and by its
      active components, including epicatechin, cyanidin, quercetin, and resveratrol,
      in human Huh7 hepatoma cells by assaying cell viability assays, the activities of
      caspase 3 and caspase 7, and the expression of endoplasmic reticulum stress
      associated proteins. FDGP dramatically decreased taurodeoxycholic acid (TDCA)
      induced production of reactive oxygen species (ROS). Assessment of individual
      active components revealed that at concentrations corresponding to 300 MUg/mL
      FDGP, only quercetin demonstrated cytoprotective effects against mitochondrial
      mediated apoptosis. In contrast, increased concentrations of other individual
      polyphenolic compounds were required to produce measurable cytoprotective effect.
      Only combinations of all four polyphenolic compounds (epicatechin, cyanidin,
      quercetin, and resveratrol) restored a degree of the anti-apoptotic effects seen
      with FDGP. The pretreatment of FDGP at 30 MUg/mL concentration could reverse the
      thapsigargin-induced effects on the expression of endoplasmic reticulum stress
      associated proteins. In conclusion, FDGP reduced oxidative stress, endoplasmic
      reticulum stress, and apoptosis. The mechanisms involved in the anti-apoptotic
      effects of FDGP included reduced generation of ROS, and reduced processing of
      certain caspases. We demonstrated that quercetin, epicatechin, and cyanidin are
      active compounds within FDGP that attenuate apoptosis. These findings contribute
      to our understanding of the molecular mechanisms of anti-apoptotic and anti
      oxidant effects of grape and are expected to assist in developing clinical
      protocols to treat a variety of stress-mediated conditions.

PMID- 20699284
TI  - T1 cortical hypointensities and their association with cognitive disability in
      multiple sclerosis.
AB  - BACKGROUND: Neocortical lesions (NLs) largely contribute to the pathology of
      multiple sclerosis (MS), although their relevance in patients' disability remains
      unknown. OBJECTIVE: To assess the incidence of T(1) hypointense NLs by 3.0-Tesla
      magnetic resonance imaging (MRI) in patients with MS and examine neocortical
      lesion association with cognitive impairment. METHODS: In this case-control
      study, 21 MS patients and 21 age-, sex- and years of education-matched healthy
      volunteers underwent: (i) a neuropsychological examination rating cognitive
      impairment (Minimal Assessment of Cognitive Function in MS); (ii) a 3.0-Tesla MRI
      inclusive of an isotropic 1.0 mm(3) three-dimensional inversion prepared spoiled
      gradient-recalled-echo (3D-IRSPGR) image and T(1)- and T(2)-weighted images.
      Hypointensities on 3D-IRSPGR lying in the cortex, either entirely or partially
      were counted and association between NLs and cognitive impairment investigated.
      RESULTS: A total of 95 NLs were observed in 14 (66.7%) patients. NL+ patients
      performed poorer (p = 0.020) than NL-patients only on the delayed recall
      component of the California Verbal Learning Test. This difference lost
      statistical significance when a correction for white matter lesion volume was
      employed. CONCLUSIONS: Although T( 1) hypointense NLs may be present in a
      relatively high proportion of multiple sclerosis patients, the impact that they
      have in cognitive impairment is not independent from white matter disease.

PMID- 20699285
TI  - The effect of core stability training on balance and mobility in ambulant
      individuals with multiple sclerosis: a multi-centre series of single case
      studies.
AB  - BACKGROUND: Core stability training is popular in the management of people with
      multiple sclerosis (MS); however, scientific evidence to support its
      effectiveness is scarce. OBJECTIVE: To explore the effectiveness of core
      stability training on balance and mobility. METHOD: A multi-centre series of
      eight single case studies was undertaken. Eight ambulant individuals with stable
      MS participated in 16 face-to-face core stability training sessions, delivered by
      a neurophysiotherapist, plus a daily home exercise programme. A range of outcomes
      were measured: 10-m timed walk, 12-item MS walking scale, timed get up and go,
      functional reach tests, timed single leg stance, visual analogue scales of two
      activities, and the Activities-specific Balance Confidence Scale. RESULTS: Visual
      analysis of trend, level and slope demonstrated improvement in five subjects
      (62%) in seven measures. This was confirmed by the two standard deviation band
      method of analysis for six measures. Analysis of group data (repeated measures
      within subjects analysis of variance) indicated significant improvement between
      baseline and intervention phases for timed walk (p = 0.019), MSWS-12 Scale (p =
      0.041), forward (p = 0.015) and lateral reach (p = 0.012). In general, no further
      improvements were made following withdrawal of the intervention. CONCLUSIONS:
      This study provides preliminary evidence of the effectiveness of an 8-week core
      stability training programme in improving balance and mobility in ambulant people
      with MS. Variations in response to intervention are evident. Assessor-blinded
      randomized controlled studies are required to confirm these findings and
      determine patient characteristics which identify those who benefit most from this
      intervention.

PMID- 20699286
TI  - Emergency bypass post percutaneous atrial ablation: a case report.
AB  - A 34-year-old male undergoing percutaneous atrial ablation procedure for
      paroxysmal fibrillation required emergency sternotomy for cardiac tamponade. The
      patient had been anticoagulated and had received plavix and aspirin prior to and
      during the ablation procedure. Seven units of red cell concentrate had been
      transfused in the cardiac catherisation laboratory. On arrival in theatre, the
      patient was hypotensive, but was awake on induction of anaesthesia. No recordable
      blood pressure with non-invasive monitoring was observed. A sternotomy was
      immediately performed and, on evacuation of the pericardium, a bleeding site was
      not visible. The patient was commenced on cardiopulmonary bypass. Bleeding site
      was identified and the defect closed. The patient was weaned from cardiopulmonary
      bypass with minimal inotropic support and made an uneventful recovery. Bypass
      time was 38 minutes. A literature review showed a 1% incidence of post-ablation
      bleeding(1). The incidence of reverting to bypass for such an event has not been
      reported previously. During these procedures, it might be wise to have the
      cardiothoracic team notified while atrial ablation procedures are being performed
      in the cardiac catheterization laboratory.

PMID- 20699287
TI  - Evaluation of the Quadrox-I neonatal oxygenator with an integrated arterial
      filter.
AB  - Cardiopulmonary bypass (CPB) can be a potential cause of morbidity in patients
      for several reasons, including significantly higher gaseous microemboli (GME)
      formation than extracorporeal life support (ECLS) and physiological circulation,
      diverted blood flow from the patient via an open purge line of the arterial
      filter, and pressure drop across the oxygenator that is used in the circuit.
      Using a combined oxygenator and arterial filter may minimize these harmful
      factors and can effectively reduce the chances for postoperative morbidity. This
      study investigated the new QUADROX-i Neonatal Oxygenator (D-72145, Maquet,
      Hirrlingen, Germany) with an integrated arterial filter in terms of the
      hemodynamic properties and ability to clear GME in response to hypothermic versus
      normothermic conditions, open versus closed arterial filter purge line, and
      varying flow rates in a simulated CPB circuit identical to that of the clinical
      setting. A flow probe, pressure transducer, and Emboli Detection and
      Classification (EDAC) quantifier transducer were placed upstream and downstream
      to the oxygenator to measure changes in each parameter. The circuit was primed
      with fresh human blood with an hematocrit (Hct) of 26% diluted with Ringer's
      lactate solution. Five milliliters of air were injected proximal to the venous
      cardiotomy reservoir, under non-pulsatile perfusion, with flow rates of 500
      ml/min, 750 ml/min, and 1000 ml/min. A total of 8 air bolus injections were made
      at each individual set of conditions for a total of 96 injections. Results showed
      that the QUADROX-i Neonatal Oxygenator with an integrated filter has excellent
      hemodynamic properties with extremely low pressure drops and blood flow diverted
      from the patient, as well as high rates of GME capturing. The arterial filter
      purge line has a significant effect on the degree of blood flow diverted from the
      patient (p < 0.001), but does not affect pressure drop across the oxygenator.

PMID- 20699288
TI  - Life cycle assessment of a road safety product made with virgin and recycled
      HDPE.
AB  - The present study aims at evaluating the potential environmental impact of using
      recycled high-density polyethylene (HDPE) in the production of an anti-glare
      lamella (AGL), a road safety device currently manufactured from virgin (not
      recycled) polymer. The impact was evaluated using the life cycle assessment (LCA)
      technique and comparing two alternative systems: current AGL, manufactured from
      virgin HDPE, and optional AGL, made with recycled HDPE obtained from post
      consumer packages. The AGL manufacturing phase was found to be responsible for
      most of the impacts in both systems, with the production of the raw material
      being the largest contributor for that phase. The present study makes a
      contribution to the problem of developing value-added products made from post
      consumer polymeric recyclates.

PMID- 20699289
TI  - Replication of urban innovations - prioritization of strategies for the
      replication of Dhaka's community-based decentralized composting model.
AB  - Dhaka's community-based decentralized composting (DCDC) is a successful
      demonstration of solid waste management by adopting low-cost technology, local
      resources community participation and partnerships among the various actors
      involved. This paper attempts to understand the model, necessary conditions,
      strategies and their priorities to replicate DCDC in the other developing cities
      of Asia. Thirteen strategies required for its replication are identified and
      assessed based on various criteria, namely transferability, longevity, economic
      viability, adaptation and also overall replication. Priority setting by multi
      criteria analysis by applying analytic hierarchy process revealed that immediate
      transferability without long-term and economic viability consideration is not
      advisable as this would result in unsustainable replication of DCDC. Based on the
      analysis, measures to ensure the product quality control; partnership among
      stakeholders (public-private-community); strategies to achieve better involvement
      of the private sector in solid waste management (entrepreneurship in approach);
      simple and low-cost technology; and strategies to provide an effective interface
      among the complementing sectors are identified as important strategies for its
      replication.

PMID- 20699290
TI  - Life cycle assessment of integrated municipal solid waste management systems,
      taking account of climate change and landfill shortage trade-off problems.
AB  - Steps taken to counter the climate change problem have a significant impact on
      the municipal solid waste management (MSW) sector, which must tackle regional
      environmental problems such as the shortage of sanitary landfills, especially in
      Japan. Moreover, greenhouse gas emissions and final disposal have a trade-off
      relationship. Therefore, alleviation of both these environmental problems is
      difficult, and Japanese local municipalities are anxious for action to solve
      these problems and reduce treatment costs. Although ambitious waste management
      measures have been enacted in many countries, they appear to lack a holistic view
      and do not adopt a life cycle approach. Therefore, it is important to reconstruct
      the MSW management system, taking into account environmental and economic
      aspects. In the present study, life cycle assessment and mathematical modelling
      were used to seek ways of redesigning the MSW management system in order to
      minimize environmental impacts and/or reduce treatment costs. One economic block
      was selected as the study area (Iwate Prefecture in Japan). The life cycle
      inventory and costs data for every MSW transportation and treatment process in
      this region were collected and processed. Then, taking account of geographic
      information, an optimal solution for the minimization of environmental impact or
      treatment costs was derived. To solve the trade-off problem, a sensitivity
      analysis was conducted to find optimal reduction targets for climate change and
      final disposal.

PMID- 20699291
TI  - Magnetic separation of coal fly ash from Bulgarian power plants.
AB  - Fly ash from three coal-burning power plants in Bulgaria: 'Maritza 3',
      'Republika' and 'Rousse East' were subjected to wet low-intensity magnetic
      separation. The tests were performed at different combinations of magnetic field
      intensity, flow velocity and diameter of matrix elements. It was found that all
      parameters investigated affected the separation efficiency, but their influence
      was interlinked and was determined by the properties of the material and the
      combination of other conditions. Among the fly ash characteristics, the most
      important parameters, determining the magnetic separation applicability, were
      mineralogical composition and distribution of minerals in particles. The main
      factors limiting the process were the presence of paramagnetic Fe-containing
      mineral and amorphous matter, and the existence of poly-mineral particles and
      aggregates of magnetic and non-magnetic particles. It was demonstrated that the
      negative effect of both factors could be considerably limited by the selection of
      a proper set of separation conditions. The dependences between concentration of
      ferromagnetic iron in the ash, their magnetic properties and magnetic fraction
      yields were studied. It was experimentally proved that, for a certain set of
      separation conditions, the yields of magnetic fractions were directly
      proportional to the saturation magnetization of the ferromagnetic components of
      the ash. The main properties of typical magnetic and non-magnetic fractions were
      studied.

PMID- 20699292
TI  - Factors influencing municipal solid waste generation in China: a multiple
      statistical analysis study.
AB  - A relationship between the waste production and socio-economic factors is
      essential in waste management. In the present study, the factors influencing
      municipal solid waste generation in China were investigated by multiple
      statistical analysis. Twelve items were chosen for investigation: GDP, per capita
      GDP, urban population, the proportion of urban population, the area of urban
      construction, the area of paved roads, the area of urban gardens and green areas,
      the number of the large cities, annual per capita disposable income of urban
      households, annual per capita consumption expenditure of urban households, total
      energy consumption and annual per capital consumption for households. Two
      methodologies from multiple statistical analysis were selected; specifically
      principal components analysis (PCA) and cluster analysis (CA). Three new
      dimensions were identified by PCA: component 1: economy and urban development;
      component 2: energy consumption; and component 3: urban scale. The three
      components together accounted for 99.1% of the initial variance. The results show
      that economy and urban development are important items influencing MSW
      generation. The proportion of urban population and urban population had the
      highest loadings in all factors. The relationship between growth of gross
      domestic product (GDP) and production of MSW was not as clear-cut as often
      assumed in China, a situation that is more likely to apply to developed
      countries. Energy consumption was another factor considered in our study of MSW
      generation. In addition, the annual MSW quantity variation was investigated by
      cluster analysis.

PMID- 20699293
TI  - Life cycle assessment of solid waste management strategies in a chlor-alkali
      production facility.
AB  - The waste management of a chlor-alkali and calcium chloride industrial facility
      from southern Chile was the object of this study. The main solid waste materials
      generated in these processes are brine sediments and calcium chloride sediments,
      respectively. Both residues are mixed in the liquid phase and filtered in a press
      filter, obtaining a final low humidity solid waste, called 'mixed sediments',
      which is disposed of in an industrial landfill as non-hazardous waste. The aim of
      the present study was to compare by means of LCA, the current waste management
      option of the studied chlor-alkali facility, namely landfill disposal, with two
      new possible options: the reuse of the mixed sediments as mineral additive in
      compost and the use of brine sediments as an unconventional sorbent for the
      removal of heavy metals from wastewater. The functional unit was defined as 1
      tonne of waste being managed. To perform this evaluation, software SimaPro 7.0
      was used, selecting the Ecoindicator 99 and CML 2000 methodologies for impact
      evaluation. The obtained results indicate that the use of brine sediments as a
      novel material for the removal of heavy metals from wastewater (scenario 3)
      presented environmental benefits when compared with the waste management option
      of sediments landfilling (scenario 1). The avoided environmental loads, generated
      by the substitution of activated granular carbon and the removal of Cu and Zn
      from wastewater in the treatment process generated positive environmental
      impacts, enhancing the environmental performance of scenario 3.

PMID- 20699294
TI  - An interview with Shin-Ichi Nishikawa. Interview by Kathryn Senior.

PMID- 20699295
TI  - Connecting muscles to tendons: tendons and musculoskeletal development in flies
      and vertebrates.
AB  - The formation of the musculoskeletal system represents an intricate process of
      tissue assembly involving heterotypic inductive interactions between tendons,
      muscles and cartilage. An essential component of all musculoskeletal systems is
      the anchoring of the force-generating muscles to the solid support of the
      organism: the skeleton in vertebrates and the exoskeleton in invertebrates. Here,
      we discuss recent findings that illuminate musculoskeletal assembly in the
      vertebrate embryo, findings that emphasize the reciprocal interactions between
      the forming tendons, muscle and cartilage tissues. We also compare these events
      with those of the corresponding system in the Drosophila embryo, highlighting
      distinct and common pathways that promote efficient locomotion while preserving
      the form of the organism.

PMID- 20699296
TI  - The control of axillary meristem fate in the maize ramosa pathway.
AB  - Plant axillary meristems are composed of highly organized, self-renewing stem
      cells that produce indeterminate branches or terminate in differentiated
      structures, such as the flowers. These opposite fates, dictated by both genetic
      and environmental factors, determine interspecific differences in the
      architecture of plants. The Cys(2)-His(2) zinc-finger transcription factor
      RAMOSA1 (RA1) regulates the fate of most axillary meristems during the early
      development of maize inflorescences, the tassel and the ear, and has been
      implicated in the evolution of grass architecture. Mutations in RA1 or any other
      known members of the ramosa pathway, RAMOSA2 and RAMOSA3, generate highly
      branched inflorescences. Here, we report a genetic screen for the enhancement of
      maize inflorescence branching and the discovery of a new regulator of meristem
      fate: the RAMOSA1 ENHANCER LOCUS2 (REL2) gene. rel2 mutants dramatically increase
      the formation of long branches in ears of both ra1 and ra2 mutants. REL2 encodes
      a transcriptional co-repressor similar to the TOPLESS protein of Arabidopsis,
      which is known to maintain apical-basal polarity during embryogenesis. REL2 is
      capable of rescuing the embryonic defects of the Arabidopsis topless-1 mutant,
      suggesting that REL2 also functions as a transcriptional co-repressor throughout
      development. We show by genetic and molecular analyses that REL2 physically
      interacts with RA1, indicating that the REL2/RA1 transcriptional repressor
      complex antagonizes the formation of indeterminate branches during maize
      inflorescence development. Our results reveal a novel mechanism for the control
      of meristem fate and the architecture of plants.

PMID- 20699297
TI  - The Bicoid gradient is shaped independently of nuclei.
AB  - Morphogen gradients provide embryos with positional information, yet how they
      form is not understood. Binding of the morphogen to receptors could affect the
      formation of the morphogen gradient, in particular if the number of morphogen
      binding sites changes with time. For morphogens that function as transcription
      factors, the final distribution can be heavily influenced by the number of
      nuclear binding sites. Here, we have addressed the role of the increasing number
      of nuclei during the formation of the Bicoid gradient in embryos of Drosophila
      melanogaster. Deletion of a short stretch of sequence in Bicoid impairs its
      nuclear accumulation. This effect is due to a approximately 4-fold decrease in
      nuclear import rate and a approximately 2-fold reduction in nuclear residence
      time compared with the wild-type protein. Surprisingly, the shape of the
      resulting anterior-posterior gradient as well as the centre-surface distribution
      are indistinguishable from those of the normal gradient. This suggests that
      nuclei do not shape the Bicoid gradient but instead function solely during its
      interpretation.

PMID- 20699298
TI  - The occipital lateral plate mesoderm is a novel source for vertebrate neck
      musculature.
AB  - In vertebrates, body musculature originates from somites, whereas head muscles
      originate from the cranial mesoderm. Neck muscles are located in the transition
      between these regions. We show that the chick occipital lateral plate mesoderm
      has myogenic capacity and gives rise to large muscles located in the neck and
      thorax. We present molecular and genetic evidence to show that these muscles not
      only have a unique origin, but additionally display a distinct temporal
      development, forming later than any other muscle group described to date. We
      further report that these muscles, found in the body of the animal, develop like
      head musculature rather than deploying the programme used by the trunk muscles.
      Using mouse genetics we reveal that these muscles are formed in trunk muscle
      mutants but are absent in head muscle mutants. In concordance with this
      conclusion, their connective tissue is neural crest in origin. Finally, we
      provide evidence that the mechanism by which these neck muscles develop is
      conserved in vertebrates.

PMID- 20699299
TI  - A novel sternal closure technique with implants suitable for complex dehiscences.
AB  - A novel sternum stabilization implant system is presented in a complex clinical
      case with previous pseudarthroses. The authors used the advanced closure system
      Sternal Talon of KLS Martin group and arranged 1 double and 2 single implants in
      an atypical fashion to fit the patient's needs. One year later follow up has not
      revealed any recurrence of pain or pseudarthrotic signs such as crepitation.

PMID- 20699300
TI  - Loop-anchor purse-string closure of gastrotomy in NOTES(R) procedures: survival
      studies in a porcine model.
AB  - INTRODUCTION: Transgastric NOTES((r)) procedures remain without a simple method
      to close the gastrotomy. In four survival swine studies, we have tested a novel
      gastric closure device: the loop-anchor purse-string (LAPS) closure system.
      METHODS: In four anesthetized pigs, an endoscopic gastrotomy was performed. Four
      loop anchors were arrayed in a 2-cm square pattern around the gastrotomy. The
      endoscope was passed into the abdominal cavity, and the gastrotomy was cinched
      closed. RESULTS: Procedure times ranged from 50-180 minutes. Three pigs survived
      14 days. One animal was sacrificed early due to signs of sepsis. Another animal
      developed fevers and was treated with antibiotics. At necropsy, there were no
      abscesses, including in the septic animal. Histologic examination revealed
      evidence of healing in all animals. DISCUSSION: The LAPS system holds promise
      with early success in an animal model. Future human studies are needed to
      determine viability as a human visceral closure device.

PMID- 20699301
TI  - ProbKnot: fast prediction of RNA secondary structure including pseudoknots.
AB  - It is a significant challenge to predict RNA secondary structures including
      pseudoknots. Here, a new algorithm capable of predicting pseudoknots of any
      topology, ProbKnot, is reported. ProbKnot assembles maximum expected accuracy
      structures from computed base-pairing probabilities in O(N(2)) time, where N is
      the length of the sequence. The performance of ProbKnot was measured by comparing
      predicted structures with known structures for a large database of RNA sequences
      with fewer than 700 nucleotides. The percentage of known pairs correctly
      predicted was 69.3%. Additionally, the percentage of predicted pairs in the known
      structure was 61.3%. This performance is the highest of four tested algorithms
      that are capable of pseudoknot prediction. The program is available for download
      at: http://rna.urmc.rochester.edu/RNAstructure.html.

PMID- 20699302
TI  - Nucleotides that are essential but not conserved; a sufficient L-tryptophan site
      in RNA.
AB  - Conservation is often used to define essential sequences within RNA sites.
      However, conservation finds only invariant sequence elements that are necessary
      for function, rather than finding a set of sequence elements sufficient for
      function. Biochemical studies in several systems-including the hammerhead
      ribozyme and the purine riboswitch-find additional elements, such as loop-loop
      interactions, required for function yet not phylogenetically conserved. Here we
      define a critical test of sufficiency: We embed a minimal, apparently sufficient
      motif for binding the amino acid tryptophan in a random-sequence background and
      ask whether we obtain functional molecules. After a negative result, we use a
      combination of three-dimensional structural modeling, selection, designed
      mutations, high-throughput sequencing, and bioinformatics to explore functional
      insufficiency. This reveals an essential unpaired G in a diverse structural
      context, varied sequence, and flexible distance from the invariant internal loop
      binding site identified previously. Addition of the new element yields a
      sufficient binding site by the insertion criterion, binding tryptophan in 22 out
      of 23 tries. Random insertion testing for site sufficiency seems likely to be
      broadly revealing.

PMID- 20699303
TI  - Missense suppressor mutations in 16S rRNA reveal the importance of helices h8 and
      h14 in aminoacyl-tRNA selection.
AB  - The molecular basis of the induced-fit mechanism that determines the fidelity of
      protein synthesis remains unclear. Here, we isolated mutations in 16S rRNA that
      increase the rate of miscoding and stop codon read-through. Many of the mutations
      clustered along interfaces between the 30S shoulder domain and other parts of the
      ribosome, strongly implicating shoulder movement in the induced-fit mechanism of
      decoding. The largest subset of mutations mapped to helices h8 and h14. These
      helices interact with each other and with the 50S subunit to form bridge B8.
      Previous cryo-EM studies revealed a contact between h14 and the switch 1 motif of
      EF-Tu, raising the possibility that h14 plays a direct role in GTPase activation.
      To investigate this possibility, we constructed both deletions and insertions in
      h14. While ribosomes harboring a 2-base-pair (bp) insertion in h14 were
      completely inactive in vivo, those containing a 2-bp deletion retained activity
      but were error prone. In vitro, the truncation of h14 accelerated GTP hydrolysis
      for EF-Tu bearing near-cognate aminoacyl-tRNA, an effect that can largely account
      for the observed miscoding in vivo. These data show that h14 does not help
      activate EF-Tu but instead negatively controls GTP hydrolysis by the factor. We
      propose that bridge B8 normally acts to counter inward rotation of the shoulder
      domain; hence, mutations in h8 and h14 that compromise this bridge decrease the
      stringency of aminoacyl-tRNA selection.

PMID- 20699304
TI  - Temperature changes and the risk of cardiac events.

PMID- 20699306
TI  - Adequacy of authors' replies to criticism raised in electronic letters to the
      editor: cohort study.
AB  - OBJECTIVE: To investigate whether substantive criticism in electronic letters to
      the editor, defined as a problem that could invalidate the research or reduce its
      reliability, is adequately addressed by the authors. DESIGN: Cohort study.
      SETTING: BMJ between October 2005 and September 2007. Inclusion criteria Research
      papers generating substantive criticism in the rapid responses section on
      bmj.com. MAIN OUTCOME MEASURES: Severity of criticism (minor, moderate, or major)
      as judged by two editors and extent to which the criticism was addressed by
      authors (fully, partly, or not) as judged by two editors and the critics.
      RESULTS: A substantive criticism was raised against 105 of 350 (30%, 95%
      confidence interval 25% to 35%) included research papers, and of these the
      authors had responded to 47 (45%, 35% to 54%). The severity of the criticism was
      the same in those papers as in the 58 without author replies (mean score 2.2 in
      both groups, P=0.72). For the 47 criticisms with replies, there was no relation
      between the severity of the criticism and the adequacy of the reply, neither as
      judged by the editors (P=0.88 and P=0.95, respectively) nor by the critics
      (P=0.83; response rate 85%). However, the critics were much more critical of the
      replies than the editors (average score 2.3 v 1.4, P<0.001). CONCLUSIONS: Authors
      are reluctant to respond to criticisms of their work, although they are not less
      likely to respond when criticisms are severe. Editors should ensure that authors
      take relevant criticism seriously and respond adequately to it.

PMID- 20699307
TI  - Sarcopenia.

PMID- 20699305
TI  - Short term effects of temperature on risk of myocardial infarction in England and
      Wales: time series regression analysis of the Myocardial Ischaemia National Audit
      Project (MINAP) registry.
AB  - OBJECTIVE: To examine the short term relation between ambient temperature and
      risk of myocardial infarction. DESIGN: Daily time series regression analysis.
      SETTING: 15 conurbations in England and Wales. PARTICIPANTS: 84,010 hospital
      admissions for myocardial infarction recorded in the Myocardial Ischaemia
      National Audit Project during 2003-6 (median 57 events a day). MAIN OUTCOME
      MEASURES: Change in risk of myocardial infarction associated with a 1 degrees C
      difference in temperature, including effects delayed by up to 28 days. RESULTS:
      Smoothed graphs revealed a broadly linear relation between temperature and
      myocardial infarction, which was well characterised by log-linear models without
      a temperature threshold: each 1 degrees C reduction in daily mean temperature was
      associated with a 2.0% (95% confidence interval 1.1% to 2.9%) cumulative increase
      in risk of myocardial infarction over the current and following 28 days, the
      strongest effects being estimated at intermediate lags of 2-7 and 8-14 days:
      increase per 1 degrees C reduction 0.6% (95% confidence interval 0.2% to 1.1%)
      and 0.7% (0.3% to 1.1%), respectively. Heat had no detrimental effect. Adults
      aged 75-84 and those with previous coronary heart disease seemed more vulnerable
      to the effects of cold than other age groups (P for interaction 0.001 or less in
      each case), whereas those taking aspirin were less vulnerable (P for interaction
      0.007). CONCLUSIONS: Increases in risk of myocardial infarction at colder ambient
      temperatures may be one driver of cold related increases in overall mortality,
      but an increased risk of myocardial infarction at higher temperatures was not
      detected. The risk of myocardial infarction in vulnerable people might be reduced
      by the provision of targeted advice or other interventions, triggered by
      forecasts of lower temperature.

PMID- 20699308
TI  - Chocolate and blood pressure. Chocolate dose may be too much.

PMID- 20699309
TI  - Congestive heart failure. Advances in management.

PMID- 20699310
TI  - Performance indicators. How valid are the indicators?

PMID- 20699311
TI  - Congestive heart failure. Don't forget rehabilitation.

PMID- 20699312
TI  - Private finance initiative. Who owns these PFI contracts?

PMID- 20699313
TI  - Ruling on mercy killing. Suicide and euthanasia paradox.

PMID- 20699314
TI  - Expert witnesses. Hearings in camera are bad public policy.

PMID- 20699315
TI  - Public finance indiscretion.

PMID- 20699316
TI  - Stroke and endarterectomy. Pathway for transient ischaemic attacks.

PMID- 20699317
TI  - Rudeness at work. It's rude to argue?

PMID- 20699318
TI  - Sharing summary care records. Same risks whichever way.

PMID- 20699319
TI  - Sharing summary care records. Results from Scottish emergency care summary.

PMID- 20699320
TI  - Sharing summary care records. What about advance directives?

PMID- 20699321
TI  - Health workers fear cholera outbreak in Pakistan.

PMID- 20699322
TI  - Moscow smog and nationwide heat wave claim thousands of lives.

PMID- 20699324
TI  - Constitutive activity of serotonin 2C receptors at G protein-independent
      signaling: modulation by RNA editing and antidepressants.
AB  - Serotonin (5-HT)(2C) receptor is a G(q)-coupled receptor exhibiting a high degree
      of constitutive activity toward phospholipase C effector pathway, a process
      regulated by receptor mRNA editing. In addition to G protein-dependent signaling,
      5-HT(2C) receptors also activate the extracellular signal-regulated kinase (ERK)
      1/2 pathway independently of receptor coupling to G proteins. Constitutive
      activity at ERK signaling has not yet been explored. Transient expression of
      unedited 5-HT(2C-INI) receptors in human embryonic kidney (HEK) 293 cells
      resulted in a marked increase in ERK1/2 phosphorylation compared with
      nontransfected cells. No increase in ERK1/2 phosphorylation was measured in cells
      expressing fully edited (5-HT(2C-VGV)) receptors. Basal ERK1/2 phosphorylation in
      5-HT(2C-INI) receptor-expressing cells was abolished by 5-methyl-1-(3
      pyridylcarbamoyl)-1,2,3,5-tetrahydropyrrolo[2,3-f]indole (SB206,553), a 5-HT(2C)
      inverse agonist toward phospholipase C. This effect was prevented by the neutral
      antagonist 6-chloro-5-methyl-1-[6-(2-methylpyridin-3-yloxy)pyridin-3
      ylcarbamoyl]indoline (SB242,084), which alone did not alter basal activity.
      Similar observations were made in vivo in mouse choroid plexus, a structure rich
      in constitutively active 5-HT(2C) receptors. Reminiscent of agonist-induced
      ERK1/2 phosphorylation, basal activity in HEK 293 cells was unaffected by
      cellular depletion of Galpha(q/11) and Galpha(13) proteins but strongly reduced
      in cells expressing a dominant-negative beta-arrestin or depleted of beta
      arrestin by RNA interference and in cells expressing a dominant-negative
      calmodulin or a 5-HT(2C-INI) receptor mutant not capable of interacting with
      calmodulin. The tetracyclic antidepressants mirtazapine and mianserin likewise
      reduced basal ERK activation. On the other hand, the m-chlorophenylpiperazine
      derivative trazodone and the selective serotonin reuptake inhibitor fluoxetine
      were inactive alone but blocked 5-HT-induced ERK1/2 phosphorylation. Together,
      these data provide the first evidence of constitutive activity of a G protein
      coupled receptor toward G-independent, beta-arrestin-dependent, receptor
      signaling.

PMID- 20699325
TI  - Alcohol- and alcohol antagonist-sensitive human GABAA receptors: tracking delta
      subunit incorporation into functional receptors.
AB  - GABA(A) receptors (GABA(A)Rs) have long been a focus as targets for alcohol
      actions. Recent work suggests that tonic GABAergic inhibition mediated by
      extrasynaptic delta subunit-containing GABA(A)Rs is uniquely sensitive to ethanol
      and enhanced at concentrations relevant for human alcohol consumption. Ethanol
      enhancement of recombinant alpha4beta3delta receptors is blocked by the
      behavioral alcohol antagonist 8-azido-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5
      a][1,4]benzodiazepine-3-carboxylic acid ethyl ester (Ro15-4513), suggesting that
      EtOH/Ro15-4513-sensitive receptors mediate important behavioral alcohol actions.
      Here we confirm alcohol/alcohol antagonist sensitivity of alpha4beta3delta
      receptors using human clones expressed in a human cell line and test the
      hypothesis that discrepant findings concerning the high alcohol sensitivity of
      these receptors are due to difficulties incorporating delta subunits into
      functional receptors. To track delta subunit incorporation, we used a functional
      tag, a single amino acid change (H68A) in a benzodiazepine binding residue in
      which a histidine in the delta subunit is replaced by an alanine residue found at
      the homologous position in gamma subunits. We demonstrate that the deltaH68A
      substitution confers diazepam sensitivity to otherwise diazepam-insensitive
      alpha4beta3delta receptors. The extent of enhancement of alpha4beta3deltaH68A
      receptors by 1 MUM diazepam, 30 mM EtOH, and 1 MUM beta-carboline-3-carboxy ethyl
      ester (but not 1 MUM Zn(2+) block) is correlated in individual recordings,
      suggesting that delta subunit incorporation into recombinant GABA(A)Rs varies
      from cell to cell and that this variation accounts for the variable
      pharmacological profile. These data are consistent with the notion that delta
      subunit-incorporation is often incomplete in recombinant systems yet is necessary
      for high ethanol sensitivity, one of the features of native delta subunit
      containing GABA(A)Rs.

PMID- 20699326
TI  - Evidence for CRHR1 in multiple sclerosis using supervised machine learning and
      meta-analysis in 12,566 individuals.
AB  - The primary genetic risk factor in multiple sclerosis (MS) is the HLA-DRB1*1501
      allele; however, much of the remaining genetic contribution to MS has yet to be
      elucidated. Several lines of evidence support a role for neuroendocrine system
      involvement in autoimmunity which may, in part, be genetically determined. Here,
      we comprehensively investigated variation within eight candidate hypothalamic
      pituitary-adrenal (HPA) axis genes and susceptibility to MS. A total of 326 SNPs
      were investigated in a discovery dataset of 1343 MS cases and 1379 healthy
      controls of European ancestry using a multi-analytical strategy. Random Forests,
      a supervised machine-learning algorithm, identified eight intronic SNPs within
      the corticotrophin-releasing hormone receptor 1 or CRHR1 locus on 17q21.31 as
      important predictors of MS. On the basis of univariate analyses, six CRHR1
      variants were associated with decreased risk for disease following a conservative
      correction for multiple tests. Independent replication was observed for CRHR1 in
      a large meta-analysis comprising 2624 MS cases and 7220 healthy controls of
      European ancestry. Results from a combined meta-analysis of all 3967 MS cases and
      8599 controls provide strong evidence for the involvement of CRHR1 in MS. The
      strongest association was observed for rs242936 (OR = 0.82, 95% CI = 0.74-0.90, P
      = 9.7 * 10(-5)). Replicated CRHR1 variants appear to exist on a single associated
      haplotype. Further investigation of mechanisms involved in HPA axis regulation
      and response to stress in MS pathogenesis is warranted.

PMID- 20699328
TI  - DNA methylation analysis of multiple tissues from newborn twins reveals both
      genetic and intrauterine components to variation in the human neonatal epigenome.
AB  - Mounting evidence from both animal and human studies suggests that the epigenome
      is in constant drift over the life course in response to stochastic and
      environmental factors. In humans, this has been highlighted by a small number of
      studies that have demonstrated discordant DNA methylation patterns in adolescent
      or adult monozygotic (MZ) twin pairs. However, to date, it remains unclear when
      such differences emerge, and how prevalent they are across different tissues. To
      address this, we examined the methylation of four differentially methylated
      regions associated with the IGF2/H19 locus in multiple birth tissues derived from
      91 twin pairs: 56 MZ and 35 dizygotic (DZ). Tissues included cord blood-derived
      mononuclear cells and granulocytes, human umbilical vein endothelial cells,
      buccal epithelial cells and placental tissue. Considerable variation in DNA
      methylation was observed between tissues and between unrelated individuals. Most
      interestingly, methylation discordance was also present within twin pairs, with
      DZ pairs showing greater discordance than MZ pairs. These data highlight the
      variable contribution of both intrauterine environmental exposures and underlying
      genetic factors to the establishment of the neonatal epigenome of different
      tissues and confirm the intrauterine period as a sensitive time for the
      establishment of epigenetic variability in humans. This has implications for the
      effects of maternal environment on the development of the newborn epigenome and
      supports an epigenetic mechanism for the previously described phenomenon of
      'fetal programming' of disease risk.

PMID- 20699327
TI  - Mutant FUS proteins that cause amyotrophic lateral sclerosis incorporate into
      stress granules.
AB  - Mutations in the RNA-binding protein FUS (fused in sarcoma) are linked to
      amyotrophic lateral sclerosis (ALS), but the mechanism by which these mutants
      cause motor neuron degeneration is not known. We report a novel ALS truncation
      mutant (R495X) that leads to a relatively severe ALS clinical phenotype compared
      with FUS missense mutations. Expression of R495X FUS, which abrogates a putative
      nuclear localization signal at the C-terminus of FUS, in HEK-293 cells and in the
      zebrafish spinal cord caused a striking cytoplasmic accumulation of the protein
      to a greater extent than that observed for recessive (H517Q) and dominant (R521G)
      missense mutants. Furthermore, in response to oxidative stress or heat shock
      conditions in cultures and in vivo, the ALS-linked FUS mutants, but not wild-type
      FUS, assembled into perinuclear stress granules in proportion to their
      cytoplasmic expression levels. These findings demonstrate a potential link
      between FUS mutations and cellular pathways involved in stress responses that may
      be relevant to altered motor neuron homeostasis in ALS.

PMID- 20699329
TI  - Effects of siltuximab on the IL-6-induced signaling pathway in ovarian cancer.
AB  - PURPOSE: To explore potential therapeutic strategies for interrupting the
      interleukin-6 (IL-6) signaling pathway, we measured IL-6 expression in ovarian
      cancer tissues, and evaluated the effects of a monoclonal anti-IL-6 antibody;
      siltuximab (CNTO 328), on levels of IL-6-induced Stat3 phosphorylation, Stat3
      nuclear translocation, and Stat3 downstream antiapoptotic genes. We then looked
      for enhancing paclitaxel sensitivity in multidrug-resistant ovarian cancer cell
      lines. EXPERIMENTAL DESIGN: Expressions of IL-6 in ovarian cancer patient
      specimens were assessed by immunohistochemistry. Effects of siltuximab on IL-6
      induced activation of Stat3 in an ovarian cancer cell line were determined by
      Western blot and real-time analysis of Stat3 nucleocytoplasmic translocation.
      Influence of combination of siltuximab and paclitaxel on tumor growth was
      evaluated in a xenograft mouse mode in vivo. RESULTS: Metastatic and drug
      resistant recurrent tumors have significantly higher IL-6 expression when
      compared with the matched primary tumors. Siltuximab specifically suppressed IL-6
      induced Stat3 phosphorylation and Stat3 nuclear translocation. Treatment with
      siltuximab significantly decreased the levels of Stat3 downstream proteins such
      as MCL-1, Bcl-X(L), and survivin. Treatment with siltuximab reduced expression of
      multiple IL-6-induced genes in these cell lines. Furthermore, siltuximab
      increased the cytotoxic effects of paclitaxel in a paclitaxel resistant ovarian
      cancer cell line in vitro, but combination therapy with siltuximab did not have a
      significant effect on paclitaxel resistant tumor growth in vivo. CONCLUSIONS:
      These results show that siltuximab effectively block the IL-6 signaling pathways
      and IL-6-induced gene expression. Blockage of IL-6 signaling may provide benefits
      for the treatment of ovarian cancer.

PMID- 20699330
TI  - Treatment adherence of cancer patients to orally administered chemotherapy:
      insights from a Greek study using a self-reported questionnaire.
AB  - PURPOSE: The aim of this prospective observational study was to investigate the
      patterns of treatment adherence to orally administered chemotherapy of patients
      being treated for cancer. METHODS: Patients were asked to participate in the
      survey during their visits to the study centers' pharmacists or doctors to obtain
      their oral medication from April 2008 until May 2009. The data were collected
      using a self-reported anonymous 7-page long questionnaire, which contained
      questions about their demographic profile, disease and treatment characteristics,
      and side-effects and adherence information, both intentional and nonintentional.
      RESULTS: 99 Patients completed the questionnaire. Missing values ranged from 1%
      to 8%. Unintended nonadherence to therapy was reported by 19 patients. The most
      important factor correlating with unintended nonadherence was the patient's
      belief regarding treatment effectiveness since only 16.7% of the patients
      believing that their treatment is effective reported nonadherence as opposed to
      62.5% for those that did not believe that treatment is effective (p=0.03).
      Intentional nonadherence was reported by 14 patients The most important factor
      correlating to intentional nonadherence was time since disease diagnosis, as
      nonadherence was reported by 33.3% of the patients having the disease less than 6
      months, compared to 16.7% for those between 6 and 24 months and 8.3% for those
      between 2 and 5 years (p=0.01). CONCLUSION: Greek patients seem to have similar
      nonadherence pattern as in other countries. Confidence in treatment efficacy
      appeared as a significant adherence determinant.

PMID- 20699331
TI  - Oxaliplatin-induced acute thrombocytopenia.
AB  - We describe a patient who experienced immediate onset severe thrombocytopenia as
      part of a hypersensitivity reaction to oxaliplatin, following substantial
      relatively uncomplicated previous exposure to the drug. We review other reports
      of acute hematological toxicity from oxaliplatin. We draw attention to the
      important need for vigilance when patients develop unusual acute symptoms during
      or shortly after oxaliplatin infusion.

PMID- 20699332
TI  - Comparative parallel assessment of a transfer device in reducing 5-fluorouracil
      environmental contamination inside positive air pressure isolators.
AB  - The environmental contamination of the antineoplastic drugs circuit, due to the
      centralization of preparation and the increased number of the patients treated,
      brought about a new occupational hazard: the chronic exposure to low doses of
      antineoplastic drugs. The rationalization of the hospital budgets imposes a
      meticulous assessment of the devices available for the preparation, in order to
      justify their interest, even their cost. A prospective comparative study with
      parallel arms was led inside the Pharmacy of the Institut de Cancerologie de la
      Loire in order to evaluate the Spike Swan(r), a transfer device. The aim was to
      assess the Spike Swan(r) effectiveness. The antineoplastic drugs environmental
      contamination within the isolators is considered as a potential starting point
      for a larger dissemination of cytotoxic products. Therefore, the primary endpoint
      was the surface contamination level with 5-fluorouracil and the comparator was
      the standard preparation technique using needles and aeration needles. This study
      did not show significant effectiveness for the Spike Swan(r) in reducing surface
      contamination. Nevertheless, this device could be used to prepare large volumes
      and to secure occasional handlers, because it is easy to handle.

PMID- 20699333
TI  - Association between occupational exposure levels of antineoplastic drugs and work
      environment in five hospitals in Japan.
AB  - PURPOSE: The aim of the present study was to evaluate the measurement of
      contamination by antineoplastic drugs for safer handling of such drugs by medical
      workers. We investigated the relationship between the contamination level of
      antineoplastic drugs and the conditions of their handling. METHODS: Air samples
      and wipe samples were collected from equipment in the preparation rooms of five
      hospitals (hospitals A-E). These samples were subjected to measurement of the
      amounts of cyclophosphamide (CPA), fluorouracil (5FU), gemcitabine (GEM), and
      platinum-containing drugs (Pt). Twenty-four-hour urine samples were collected
      from the pharmacists who handled or audited, the antineoplastic drugs were
      analyzed for CPA and Pt. RESULTS: Pt was detected from air samples inside BSC in
      hospital B. Antineoplastic drugs were detected from wipe samples of the BSC in
      hospitals A, B, D, and E and of other equipment in the preparation rooms in
      hospitals A, B, C, and D. Cyclophosphamide and 5FU were detected from wipe
      samples of the air-conditioner filter in hospital A, and CPA was detected from
      that in hospital D. Cyclophosphamide was detected from urine samples of workers
      in hospitals B, D, and E. CONCLUSION: The contamination level of antineoplastic
      drugs was suggested to be related with the amount of drugs handled, cleaning
      methods of the equipment, and the skill level of the technique of maintaining
      negative pressure inside a vial. In order to reduce the contamination and
      exposure to antineoplastic drugs in the hospital work environment very close to
      zero, comprehensive safety precautions, including adequate mixing and cleaning
      methods was required in addition to BSC and closed system device.

PMID- 20699334
TI  - Balancing biosynthesis and bioenergetics: metabolic programs in oncogenesis.
AB  - Cancer biologists' search for new chemotherapy targets is reinvigorating the
      study of how cancer cell metabolism determines both oncogenic potential and
      chemotherapeutic responses. Oncogenic metabolic programs support the
      bioenergetics associated with resistance to programed cell death and provide
      biosynthetic building blocks for cell growth and mitogenesis. Both signal
      transduction pathway activation and direct mutations in key metabolic enzymes can
      activate the metabolic programs that support cancer cell growth. Cancer
      associated metabolic programs include glycolysis, glutamine oxidation, and fatty
      acid metabolism. Recent observations are revealing the regulatory mechanisms that
      activate cancer-associated metabolism, and the competitive advantages provided to
      transformed cells by their metabolic programs. In this study, we review recent
      results illustrating the mechanisms and functional impact of each of these
      oncogenic metabolic programs in cancer cell growth and survival.

PMID- 20699335
TI  - Serial polysomnography in hypnic headache.
AB  - BACKGROUND: Hypnic headache (HH) is a rare primary headache disorder
      characterized by strictly sleep-related headache attacks. Most patients are over
      the age of 50 and usually awake at the same time at night with dull bilateral
      head pain. The pathophysiology of this headache disorder is still enigmatic but
      association with rapid eye movement (REM) sleep and sleep-disordered breathing
      (SDB) has been suggested. METHODS: Six patients with HH according to the current
      International Classification of Headache Disorders (ICHD-II) criteria (code 4.5)
      were investigated. Serial polysomnography (PSG) was performed in each patient for
      four consecutive nights. RESULTS: A total of 22 HH attacks were recorded from all
      patients during PSG. Six of the monitored headache attacks arose from REM sleep;
      16 attacks, however, arose from different non-REM (NREM) sleep stages. Five
      patients showed an increased apnoea/hypopnoea index (>5), indicating obstructive
      sleep apnoea (OSA) on some but not the majority of nights. Headache onset and
      occurrence of SDB were not temporally connected. CONCLUSIONS: This prospective
      study shows that the onset of HH was not associated with sleep stage. These
      results contradict the current belief that REM sleep and SDB play a crucial role
      in the pathophysiology of HH.

PMID- 20699336
TI  - Which elements of the criteria for RA are stable over time?

PMID- 20699337
TI  - Magnetic resonance imaging assessment of the velopharyngeal mechanism at rest and
      during speech in Chinese adults and children.
AB  - PURPOSE: Recent applications of the magnetic resonance imaging (MRI) technique
      introduced accurate 3-dimensional measurements of the velopharyngeal mechanism.
      Further standardization of the data acquisition and analysis protocol was
      successfully applied to imaging adults at rest and during phonation. This study
      was designed to test and modify a noninvasive protocol for evaluating young
      children without using general anesthesia. In addition, the velopharyngeal
      structures and their maximal motion were compared between adults and children.
      METHOD: MRI data were acquired in 12 young adults and 9 children at rest and
      during speech production. Multiple measurements were made on the velopharyngeal
      and craniofacial structures as well as on the levator veli palatini muscle.
      RESULTS: Most of the ratio measurements of structural shape and maximal motion in
      the velopharyngeal and craniofacial regions were not significantly different
      between the adults and the children, despite the fact that the children had much
      smaller structures than the adults. CONCLUSION: The proportion of the
      velopharyngeal mechanism remains stable in young children and adults so that the
      motions of the velum and pharyngeal walls are adequate to close the
      velopharyngeal port completely.

PMID- 20699339
TI  - Effects of noise and speech intelligibility on listener comprehension and
      processing time of Korean-accented English.
AB  - PURPOSE: This study evaluated the effects of noise and speech intelligibility on
      the processing of speech produced from native English; high-intelligibility,
      Korean-accented English; and moderate-intelligibility, Korean-accented English
      speakers. METHOD: Both listener comprehension, determined by accuracy judgment on
      true/false sentences, and processing time, estimated from response latency, were
      assessed under the following 3 conditions: quiet, +10 dB signal-to-noise ratio
      (SNR), and +5 dB SNR. Fifty-four monolingual, English-speaking adults served as
      the listeners for this study. RESULTS: While noise did not affect the time it
      took to process foreign-accented speech, it decreased the comprehension of the
      foreign-accented speech more so than the native speech. Decreasing English
      intelligibility also resulted in reduced listener comprehension. In addition, the
      processing time needed to comprehend the intended message depended on the
      intelligibility of the foreign-accented speaker. Listener comprehension
      negatively correlated with processing time. CONCLUSION: The findings suggest that
      decreased speech intelligibility and adverse listening conditions can be major
      challenges for effective communication between foreign-accented speakers and
      native listeners. The results also indicate that foreign-accented speech requires
      more effortful processing relative to native speech under certain conditions,
      affecting both comprehension and processing efficiency.

PMID- 20699338
TI  - Nebulized isotonic saline versus water following a laryngeal desiccation
      challenge in classically trained sopranos.
AB  - PURPOSE: To examine the effects of nebulized isotonic saline (IS) versus sterile
      water (SW) on self-perceived phonatory effort (PPE) and phonation threshold
      pressure (PTP) following a surface laryngeal dehydration challenge in classically
      trained sopranos. METHOD: In a double-blind, within-subject crossover design, 34
      sopranos breathed dry air (relative humidity < 1%) transorally for 15 min and
      then nebulized 3 mL of IS or SW, or experienced a no-treatment control condition
      over 3 consecutive weeks. PPE and PTP were measured every 15 min from baseline
      through 2 hr postdesiccation. RESULTS: PPE increased significantly following the
      laryngeal desiccation challenge in all 3 treatment conditions (p < .01). After
      nebulization, PPE returned to baseline for the IS condition only. For the SW and
      control conditions, PPE remained above baseline during the 2 hr after
      desiccation. No statistically significant changes in PTP following laryngeal
      desiccation were observed, although values for the IS condition remained below
      baseline for nearly 2 hr after nebulization. PPE and PTP were not significantly
      correlated. CONCLUSIONS: Following a laryngeal surface dehydration challenge,
      classically trained sopranos reported increased vocal effort that persisted for
      at least 2 hr. Compared with SW, nebulized IS showed promise as an effective way
      to remediate the adverse, self-perceived effects of laryngeal desiccation.

PMID- 20699340
TI  - Swallow characteristics in patients with oculopharyngeal muscular dystrophy.
AB  - PURPOSE: This prospective investigation evaluates oral weakness and its impact on
      swallow function, weight, and quality of life in patients with oculopharyngeal
      muscular dystrophy (OPMD). METHOD: Intraoral pressure, swallow pressure, and
      endurance were measured using an Iowa Oral Performance Instrument in participants
      with OPMD and matched controls. Timed water swallow, weight, and quality of life
      were also assessed. RESULTS: Participants with OPMD were weaker than controls.
      Oral weakness impacted strength, swallow pressure, swallow capacity, swallow
      volume, swallow time, and quality of life. Tongue endurance was not affected by
      oral weakness. CONCLUSION: This investigation provides further insight into the
      swallow function of patients with myopathic disease. Muscle fiber loss leads to
      weakness, which results in reductions in swallow function and quality of life.
      Weight and endurance are not greatly altered.

PMID- 20699341
TI  - Articulatory-to-acoustic relations in response to speaking rate and loudness
      manipulations.
AB  - PURPOSE: In this investigation, the authors determined the strength of
      association between tongue kinematic and speech acoustics changes in response to
      speaking rate and loudness manipulations. Performance changes in the kinematic
      and acoustic domains were measured using two aspects of speech production
      presumably affecting speech clarity: phonetic specification and variability.
      METHOD: Tongue movements for the vowels /ia/ were recorded in 10 healthy adults
      during habitual, fast, slow, and loud speech using three-dimensional
      electromagnetic articulography. To determine articulatory-to-acoustic relations
      for phonetic specification, the authors correlated changes in lingual
      displacement with changes in acoustic vowel distance. To determine articulatory
      to-acoustic relations for phonetic variability, the authors correlated changes in
      lingual movement variability with changes in formant movement variability.
      RESULTS: A significant positive linear association was found for kinematic and
      acoustic specification but not for kinematic and acoustic variability. Several
      significant speaking task effects were also observed. CONCLUSION: Lingual
      displacement is a good predictor of acoustic vowel distance in healthy talkers.
      The weak association between kinematic and acoustic variability raises questions
      regarding the effects of articulatory variability on speech clarity and
      intelligibility, particularly in individuals with motor speech disorders.

PMID- 20699342
TI  - Lip movement exaggerations during infant-directed speech.
AB  - PURPOSE: Although a growing body of literature has identified the positive
      effects of visual speech on speech and language learning, oral movements of
      infant-directed speech (IDS) have rarely been studied. This investigation used 3
      dimensional motion capture technology to describe how mothers modify their lip
      movements when talking to their infants. METHOD: Lip movements were recorded from
      25 mothers as they spoke to their infants and other adults. Lip shapes were
      analyzed for differences across speaking conditions. The maximum fundamental
      frequency, duration, acoustic intensity, and first and second formant frequency
      of each vowel also were measured. RESULTS: Lip movements were significantly
      larger during IDS than during adult-directed speech, although the exaggerations
      were vowel specific. All of the vowels produced during IDS were characterized by
      an elevated vocal pitch and a slowed speaking rate when compared with vowels
      produced during adult-directed speech. CONCLUSION: The pattern of lip-shape
      exaggerations did not provide support for the hypothesis that mothers produce
      exemplar visual models of vowels during IDS. Future work is required to determine
      whether the observed increases in vertical lip aperture engender visual and
      acoustic enhancements that facilitate the early learning of speech.

PMID- 20699343
TI  - Normative data for the Words-in-Noise Test for 6- to 12-year-old children.
AB  - PURPOSE: To establish normative data for children on the Words-in-Noise Test
      (WIN; R. H. Wilson, 2003; R. H. Wilson & R. McArdle, 2007). METHOD: Forty-two
      children in each of 7 age groups, ranging in age from 6 to 12 years (n=294), and
      24 young adults (age range: 18-27 years) with normal hearing for pure tones
      participated. All listeners were screened at 15 dB HL (American National
      Standards Institute, 2004) with the octave interval between 500 and 4000 Hz.
      Randomizations of WIN Lists 1, 2, and 1 or WIN Lists 2, 1, and 2 were presented
      with the noise fixed at 70 dB SPL, followed by presentation at 90 dB SPL of the
      70 Northwestern University Auditory Test No. 6 (T. W. Tillman & R. Carhart, 1966)
      words used in the WIN. Finally, the Peabody Picture Vocabulary Test-Revised (L.
      M. Dunn & L. M. Dunn, 1981) was administered. Testing was conducted in a quiet
      room. RESULTS: There were 3 main findings: (a) The biggest change in recognition
      performance occurred between the ages of 6 and 7 years; (b) from 9 to 12 years,
      recognition performance was stable; and (c) performance by young adults (18-27
      years) was slightly better (1-2 dB) than performance by the older children.
      CONCLUSION: The WIN can be used with children as young as 6 years of age;
      however, age-specific ranges of normal recognition performance must be used.

PMID- 20699344
TI  - Developing a weighted measure of speech sound accuracy.
AB  - PURPOSE: To develop a system for numerically quantifying a speaker's phonetic
      accuracy through transcription-based measures. With a focus on normal and
      disordered speech in children, the authors describe a system for differentially
      weighting speech sound errors on the basis of various levels of phonetic accuracy
      using a Weighted Speech Sound Accuracy (WSSA) score. The authors then evaluate
      the reliability and validity of this measure. METHOD: Phonetic transcriptions
      were analyzed from several samples of child speech, including preschoolers and
      young adolescents with and without speech sound disorders and typically
      developing toddlers. The new measure of phonetic accuracy was validated against
      existing measures, was used to discriminate typical and disordered speech
      production, and was evaluated to examine sensitivity to changes in phonetic
      accuracy over time. Reliability between transcribers and consistency of scores
      among different word sets and testing points are compared. RESULTS: Initial
      psychometric data indicate that WSSA scores correlate with other measures of
      phonetic accuracy as well as listeners' judgments of the severity of a child's
      speech disorder. The measure separates children with and without speech sound
      disorders and captures growth in phonetic accuracy in toddlers' speech over time.
      The measure correlates highly across transcribers, word lists, and testing
      points. CONCLUSION: Results provide preliminary support for the WSSA as a valid
      and reliable measure of phonetic accuracy in children's speech.

PMID- 20699345
TI  - Systematic studies of modified vocalization: effects of speech rate and
      instatement style during metronome stimulation.
AB  - PURPOSE: This study introduces a series of systematic investigations intended to
      clarify the parameters of the fluency-inducing conditions (FICs) in stuttering.
      METHOD: Participants included 11 adults, aged 20-63 years, with typical speech
      production skills. A repeated measures design was used to examine the
      relationships between several speech production variables (vowel duration, voice
      onset time, fundamental frequency, intraoral pressure, pressure rise time,
      transglottal airflow, and phonated intervals) and speech rate and instatement
      style during metronome-entrained rhythmic speech. RESULTS: Measures of duration
      (vowel duration, voice onset time, and pressure rise time) differed across
      different metronome conditions. When speech rates were matched between the
      control condition and metronome condition, voice onset time was the only variable
      that changed. CONCLUSION: Results confirm that speech rate and instatement style
      can influence speech production variables during the production of fluency
      inducing conditions. Future studies of normally fluent speech and of stuttered
      speech must control both features and should further explore the importance of
      voice onset time, which may be influenced by rate during metronome stimulation in
      a way that the other variables are not.

PMID- 20699346
TI  - The intonation-syntax interface in the speech of individuals with Parkinson's
      disease.
AB  - PURPOSE: This study examined the effect of Parkinson's disease (PD) on the
      intonational marking of final and nonfinal syntactic boundaries and investigated
      whether the effect of PD on intonation was sex specific. METHOD: Eight women and
      8 men with PD and 16 age- and sex-matched control participants read a passage at
      comfortable pitch, rate, and loudness. Nuclear tones from final and nonfinal
      syntactic boundaries in clauses and lists were extracted. Measures of fundamental
      frequency (F0) were made on each tone contour. RESULTS: Individuals with PD
      demonstrated impaired differentiation of syntactic boundary finality/nonfinality
      with contour direction. They produced a lower proportion of falling contours in
      final boundaries and a higher proportion of falling contours in nonfinal
      boundaries than did control participants. Although not mediated by syntax, the
      effect of PD on F0 standard deviation (F0 SD) and pitch range in semitones (PRST)
      was sex specific. Women with PD produced greater F0 SD and PRST than did men with
      PD and women without PD. Men with PD produced lower PRST than did men without PD.
      CONCLUSIONS: Impaired intonational marking of syntactic boundaries likely
      contributes to dysprosody and reduced communicative effectiveness in PD. The
      effect of PD on intonation was sex specific. The results are not fully explained
      by PD-related motor execution impairments.

PMID- 20699348
TI  - Does continuity of care matter in a health care system that lacks referral
      arrangements?
AB  - INTRODUCTION: Numerous studies have suggested that better continuity of care
      (COC) can lead to fewer emergency department (ED) visits and fewer hospital
      admissions. However, these studies were conducted in countries where patients
      have their own family physician or in countries with referral systems. This study
      aimed to determine whether the association between lower COC and increased health
      care utilization may be apparent in a health care system that lacks a family
      physician or a referral system. METHODS: The study population included a total of
      134 422 subjects who made four or more visits to physicians in 2005. Negative
      binominal regressions were performed to examine the effects of three different
      COC indices on the numbers of hospital admissions and ED visits in 2005 and in
      the subsequent year (2006). RESULTS: The data suggest that lower COC was
      associated with increased hospital admissions and ED visits in our study
      population. Compared with the high COC group, subjects in the low and medium COC
      groups had 42-82% and 39-46% more hospital admissions, respectively, as well as
      75-102% and 41-45% more ED visits, respectively, in 2005. Weaker protective
      effects of COC were also observed in the subsequent year. CONCLUSIONS: This study
      indicates that lower COC is associated with increased hospital admissions and ED
      visits, even in a health care system that lacks a referral arrangement framework.
      This suggests that improving the COC is beneficial both for patients and for the
      health care system.

PMID- 20699347
TI  - Automated measurement of vocal fold vibratory asymmetry from high-speed
      videoendoscopy recordings.
AB  - PURPOSE: In prior work, a manually derived measure of vocal fold vibratory phase
      asymmetry correlated to varying degrees with visual judgments made from laryngeal
      high-speed videoendoscopy (HSV) recordings. This investigation extended this work
      by establishing an automated HSV-based framework to quantify 3 categories of
      vocal fold vibratory asymmetry. METHOD: HSV-based analysis provided for cycle-to
      cycle estimates of left-right phase asymmetry, left-right amplitude asymmetry,
      and axis shift during glottal closure for 52 speakers with no vocal pathology
      producing comfortable and pressed phonation. An initial cross-validation of the
      automated left-right phase asymmetry measure was performed by correlating the
      measure with other objective and subjective assessments of phase asymmetry.
      RESULTS: Vocal fold vibratory asymmetry was exhibited to a similar extent in both
      comfortable and pressed phonations. The automated measure of left-right phase
      asymmetry strongly correlated with manually derived measures and moderately
      correlated with visual-perceptual ratings. Correlations with the visual
      perceptual ratings remained relatively consistent as the automated measure was
      derived from kymograms taken at different glottal locations. CONCLUSIONS: An
      automated HSV-based framework for the quantification of vocal fold vibratory
      asymmetry was developed and initially validated. This framework serves as a
      platform for investigating relationships between vocal fold tissue motion and
      acoustic measures of voice function.

PMID- 20699349
TI  - Physical fitness in northern European youth: reference values from the Latvian
      Physical Health in Youth Study.
AB  - AIMS: Physical fitness has the potential to be used as a key health determinant
      in youth. The aim of this study was to establish age- and sex-stratified
      reference values for health-related physical fitness in Latvian school-age
      children and to identify notable sex differences. METHODS: Physical fitness was
      assessed using the EUROFIT test battery. Data were gathered from schoolchildren
      aged between 6 and 17 years (n = 10,464) by a medical team using standardised
      methods (EUROFIT battery). Fitness levels, stratified by chronological age and
      sex, were computed as mean +/- SD. Each test was also analysed for differences
      between males and females in each age group. RESULTS: Boys performed better than
      girls in muscular endurance and strength, cardiorespiratory endurance, and speed
      agility fitness tests. Girls had better flexibility than boys (p < 0.001). There
      was also a more pronounced improvement in physical fitness scores with age in
      boys compared with girls. CONCLUSIONS: Physical fitness reference values were
      developed for Latvian children and adolescents. These reference values will
      permit comparisons between students during physical education lessons and provide
      a baseline against which progress in physical fitness among northern European
      youths can be compared.

PMID- 20699350
TI  - Educational inequalities in ischaemic heart disease mortality in 44,000 Norwegian
      women and men: the influence of psychosocial and behavioural factors. The HUNT
      Study.
AB  - AIMS: To investigate the influence of psychosocial and behavioural factors on
      educational inequalities in ischaemic heart disease (IHD) mortality. METHODS: A
      population-based cohort study of 44,128 women and men free of IHD aged 30 years
      and older at baseline in 1995-97. RESULTS: After adjustment for age and long
      standing illness, both women (HR 3.22, 95% CI 1.31-7.90) and men (HR 1.57, 95% CI
      1.03-2.40) who completed only primary education level (primary and lower
      secondary school) were at increased risk for IHD mortality compared to those who
      completed the tertiary education level (first and second stage of tertiary
      education). Behavioural factors explained 25% of the relative difference between
      primary and tertiary education level in IHD mortality among women and 53 % in
      men. Psychosocial factors had small influence on the relative difference in IHD
      mortality CONCLUSIONS: Findings from this study indicate that differences in
      behavioural factors contribute considerably more to inequalities in IHD mortality
      in educational levels than do psychosocial factors, and this effect seems to be
      stronger in men than women.

PMID- 20699351
TI  - Anti-aversive effects of the atypical antipsychotic, aripiprazole, in animal
      models of anxiety.
AB  - Aripiprazole is a unique antipsychotic that seems to act as a partial agonist at
      dopamine D2-receptors, contrasting with other drugs in this class, which are
      silent antagonists. Aripiprazole may also bind to serotonin receptors. Both
      neurotransmitters may play major roles in aversion-, anxiety- and panic-related
      behaviours. Thus, the present work tested the hypothesis that this antipsychotic
      could also have anti-aversive properties. Male Wistar rats received injections of
      aripiprazole (0.1-10 mg/kg) and were tested in the open field, in the elevated
      plus and T mazes (EPM and ETM, respectively) and in a contextual fear
      conditioning paradigm. Aripiprazole (1 mg/kg) increased the percentage of entries
      onto the open arms of the EPM and attenuated escape responses in the ETM. In the
      latter model, the dose of 0.1 mg/kg also decreased the latency to leave the
      enclosed arm, suggesting anxiolytic- and panicolytic-like properties. This dose
      also decreased the time spent in freezing in a contextual fear conditioning. No
      significant motor effects were observed at these doses. The present data support
      the hypothesis that aripiprazole could inhibit anxiety-related responses. Acting
      as a partial agonist at dopamine receptors, this drug could effectively treat
      schizophrenia and, in contrast with most antipsychotic drugs, alleviate aversive
      states.

PMID- 20699352
TI  - Dexamphetamine-induced reduction of P3a and P3b in healthy participants.
AB  - The reduced P3 is one of the most robust deficits involved in schizophrenia.
      Previous research with catecholaminergic agonists or releasers such as
      amphetamines have used doses too small to adequately demonstrate an effect on P3.
      In this study, we gave 0.45 mg/kg dexamphetamine to healthy volunteers (final n =
      18) using both auditory and visual three-stimulus P3 procedures. Dexamphetamine
      significantly reduced P3 amplitudes to auditory target, rare non-target and
      standard stimulus amplitudes. The reduction in auditory P3 induced by
      dexamphetamine was proportional across stimulus types to placebo P3 values. There
      were no effects of dexamphetamine on visual P3. We demonstrate a reduced auditory
      P3 similar to that seen in schizophrenia and other psychotic illnesses. This
      possibly reflects a common pathology which is hypothesized within the P3
      literature to be related to attention and working memory. Differences between
      auditory and visual P3 modulation may be related to regional variations in
      catecholamine or specifically dopamine receptor densities. One specific auditory
      P3 generator is the superior temporal cortex, an area with dopamine D(2) receptor
      enriched bands. This is contrasted with visual specific generators, such as the
      inferior temporal cortex and superior parietal cortex, which do not have these
      enriched bands.

PMID- 20699353
TI  - Attenuation of chronic mild stress-induced 'anhedonia' by asenapine is not
      associated with a 'hedonic' profile in intracranial self-stimulation.
AB  - Chronic mild stress (CMS)-induced 'anhedonia' is a predictive model of
      antidepressant activity. We assessed the reversal of CMS-induced behavioral
      changes by asenapine, the antidepressant imipramine, and the atypical
      antipsychotics olanzapine and risperidone. Secondarily, the ability of these
      agents to facilitate intracranial self-stimulation (ICSS) was assessed to ensure
      that any attenuation of CMS-induced anhedonia was not associated with an overt
      hedonic profile. After 2 weeks of CMS, male Wistar rats were administered
      asenapine (0.06-0.6 mg/kg), olanzapine (2 mg/kg), risperidone (0.5 mg/kg), or
      imipramine (10 mg/kg) by intraperitoneal injection over 5 weeks to examine their
      ability to reverse CMS-induced reductions in the intake of a sucrose solution.
      For the ICSS study, rats were trained to deliver an electrical stimulus to the
      ventral tegmental area. The effects of acute doses of subcutaneous asenapine
      (0.01-0.3 mg/kg), olanzapine (0.3 and 1 mg/kg), risperidone (0.1 and 0.3 mg/kg),
      and intraperitoneal imipramine (3-30 mg/kg), cocaine (5.0 mg/kg), or amphetamine
      (1.0 mg/kg) on ICSS were then examined. CMS significantly reduced sucrose intake
      (P < 0.001). All active agents (0.6 mg/kg asenapine, 2 mg/kg olanzapine, 0.5
      mg/kg risperidone, and 10 mg/kg imipramine) reversed the effect of CMS (all P <
      0.001). In the ICSS protocol, asenapine (0.01 and 0.03 mg/kg), olanzapine (1
      mg/kg), and risperidone (0.3 mg/kg) impaired ICSS performance, whereas positive
      controls (5 mg/kg cocaine, 1 mg/kg amphetamine) facilitated ICSS. Asenapine
      reversed CMS-induced anhedonia without facilitating ICSS, providing support for a
      role of asenapine in treating bipolar disorder and aspects of negative and/or
      affective symptoms in schizophrenia.

PMID- 20699354
TI  - Prolactin and smoking status in antipsychotic-treated patients.
AB  - Studies investigating the relationship between cigarette smoking and prolactin
      secretion in the general population have yielded inconsistent results. Many
      antipsychotic drugs increase prolactin secretion, but there are no published
      studies that have investigated the relationship between smoking and
      prolactinaemia in antipsychotic-treated patients. We obtained prolactin levels
      from 228 antipsychotic-treated patients in secondary care mental health services
      and investigated the relationship between prolactinaemia and cigarette smoking.
      Twenty-three percent (n = 52) of patients had hyperprolactinaemia. Patients
      prescribed typical or a combination of typical and atypical antipsychotics had a
      significantly higher prevalence of hyperprolactinaemia and higher mean prolactin
      concentration. Both current and ex-cigarette smokers had significantly lower mean
      prolactin levels and a lower prevalence of hyperprolactinaemia, but after
      controlling for potentially confounding variables, only current smoking status
      was a significant predictor of lower prolactin levels (OR 2.3, 95% CI 1.2 to 4.7,
      p = 0.002). In this preliminary, cross-sectional study, there was a robust
      statistical relationship between cigarette smoking and prolactinaemia. The
      mechanism(s) underpinning this association needs further investigation.

PMID- 20699355
TI  - CHMP2B mutants linked to frontotemporal dementia impair maturation of dendritic
      spines.
AB  - The highly conserved ESCRT-III complex is responsible for deformation and
      cleavage of membranes during endosomal trafficking and other cellular activities.
      In humans, dominant mutations in the ESCRT-III subunit CHMP2B cause
      frontotemporal dementia (FTD). The decade-long process leading to this cortical
      degeneration is not well understood. One possibility is that, akin to other
      neurodegenerative diseases, the pathogenic protein affects the integrity of
      dendritic spines and synapses before any neuronal death. Using confocal
      microscopy and 3D reconstruction, we examined whether expressing the FTD-linked
      mutants CHMP2B(intron5) and CHMP2B(Delta10) in cultured hippocampal neurons
      modified the number or structure of spines. Both mutants induced a significant
      decrease in the proportion of large spines with mushroom morphology, without
      overt degeneration. Furthermore, CHMP2B(Delta10) induced a drop in frequency and
      amplitude of spontaneous excitatory postsynaptic currents, suggesting that the
      more potent synapses were lost. These effects seemed unrelated to changes in
      autophagy. Depletion of endogenous CHMP2B by RNAi resulted in morphological
      changes similar to those induced by mutant CHMP2B, consistent with dominant
      negative activity of pathogenic mutants. Thus, CHMP2B is required for spine
      growth. Taken together, these results demonstrate that a mutant ESCRT-III subunit
      linked to a human neurodegenerative disease can disrupt the normal pattern of
      spine development.

PMID- 20699356
TI  - Strategies of actin reorganisation in plant cells.
AB  - Spatial-temporal flexibility of the actin filament network (F-actin) is essential
      for all basic cellular functions and is governed by a stochastic dynamic model.
      In this model, actin filaments that randomly polymerise from a pool of free actin
      are bundled with other filaments and severed by ADF/cofilin. The fate of the
      severed fragments is not known. It has been proposed that the fragments are
      disassembled and the monomeric actin recycled for the polymerisation of new
      filaments. Here, we have generated tobacco cell lines and Arabidopsis plants
      expressing the actin marker Lifeact to address the mechanisms of F-actin
      reorganisation in vivo. We found that F-actin is more dynamic in isotropically
      expanding cells and that the density of the network changes with a periodicity of
      70 seconds. The depolymerisation rate, but not the polymerisation rate, of F
      actin increases when microtubules are destabilised. New filaments can be
      assembled from shorter free cytoplasmic fragments, from the products of F-actin
      severing and by polymerisation from the ends of extant filaments. Thus,
      remodelling of F-actin might not require bulk depolymerisation of the entire
      network, but could occur via severing and end-joining of existing polymers.

PMID- 20699357
TI  - Assembly of fibrillin microfibrils governs extracellular deposition of latent TGF
      beta.
AB  - Control of the bioavailability of the growth factor TGFbeta is essential for
      tissue formation and homeostasis, yet precisely how latent TGFbeta is
      incorporated into the extracellular matrix is unknown. Here, we show that
      deposition of a large latent TGFbeta complex (LLC), which contains latent TGFbeta
      binding protein 1 (LTBP-1), is directly dependent on the pericellular assembly of
      fibrillin microfibrils, which interact with fibronectin during higher-order
      fibrillogenesis. LTBP-1 formed pericellular arrays that colocalized with
      microfibrils, whereas fibrillin knockdown inhibited fibrillar LTBP-1 and/or LLC
      deposition. Blocking alpha5beta1 integrin or supplementing cultures with heparin,
      which both inhibited microfibril assembly, disrupted LTBP-1 deposition and
      enhanced Smad2 phosphorylation. Full-length LTBP-1 bound only weakly to N
      terminal pro-fibrillin-1, but this association was strongly enhanced by heparin.
      The microfibril-associated glycoprotein MAGP-1 (MFAP-2) inhibited LTBP-1 binding
      to fibrillin-1 and stimulated Smad2 phosphorylation. By contrast, fibulin-4,
      which interacted strongly with full-length LTBP-1, did not induce Smad2
      phosphorylation. Thus, LTBP-1 and/or LLC deposition is dependent on pericellular
      microfibril assembly and is governed by complex interactions between LTBP-1,
      heparan sulfate, fibrillin-1 and microfibril-associated molecules. In this way,
      microfibrils control TGFbeta bioavailability.

PMID- 20699358
TI  - 14-3-3 sigma associates with cell surface aminopeptidase N in the regulation of
      matrix metalloproteinase-1.
AB  - Matrix metalloproteinases (MMPs) are implicated in the degradation of the
      extracellular matrix during development and tissue repair, as well as in
      pathological conditions such as tumor invasion and fibrosis. MMP expression by
      stromal cells is partly regulated by signals from the neighboring epithelial
      cells. Keratinocyte-releasable 14-3-3sigma, or stratifin, acts as a potent MMP-1
      stimulatory factor in fibroblasts. However, its mechanism of transmembrane
      signaling remains unknown. Ectodomain biotin labeling, serial affinity
      purification and mass spectroscopy analysis revealed that the stratifin
      associates with aminopeptidase N (APN), or CD13, at the cell surface. The
      transient knockdown of APN in fibroblasts eliminated the stratifin-mediated p38
      MAP kinase activation and MMP-1 expression, implicating APN in a receptor
      mediated transmembrane signaling event. Stratifin deletion studies implicated its
      C-terminus as a potential APN-binding site. Furthermore, the dephosphorylation of
      APN ectodomains reduced its binding affinity to the stratifin. The presence of a
      phosphorylated serine or threonine residue in APN has been implicated. Together,
      these findings provide evidence that APN is a novel cell surface receptor for
      stratifin and a potential target in the regulation of MMP-1 expression in
      epithelial-stromal cell communication.

PMID- 20699359
TI  - Casein kinase 1 regulates human hypoxia-inducible factor HIF-1.
AB  - Hypoxia-inducible factor 1 (HIF-1), a transcriptional activator that mediates
      cellular response to hypoxia and a promising target of anticancer therapy, is
      essential for adaptation to low oxygen conditions, embryogenesis and tumor
      progression. HIF-1 is a heterodimer of HIF-1alpha, expression of which is
      controlled by oxygen levels as well as by various oxygen-independent mechanisms,
      and HIF-1beta (or ARNT), which is constitutively expressed. In this work, we
      investigate the phosphorylation of the N-terminal heterodimerization (PAS) domain
      of HIF-1alpha and identify Ser247 as a major site of in vitro modification by
      casein kinase 1delta (CK1delta). Mutation of this site to alanine, surprisingly,
      enhanced the transcriptional activity of HIF-1alpha, a result phenocopied by
      inhibition or small interfering RNA (siRNA)-mediated silencing of CK1delta under
      hypoxic conditions. Conversely, overexpression of CK1delta or phosphomimetic
      mutation of Ser247 to aspartate inhibited HIF-1alpha activity without affecting
      its stability or nuclear accumulation. Immunoprecipitation and in vitro binding
      experiments suggest that CK1-dependent phosphorylation of HIF-1alpha at Ser247
      impairs its association with ARNT, a notion also supported by modeling the
      structure of the complex between HIF-1alpha and ARNT PAS-B domains. We suggest
      that modification of HIF-1alpha by CK1 represents a novel mechanism that controls
      the activity of HIF-1 during hypoxia by regulating the interaction between its
      two subunits.

PMID- 20699360
TI  - Lumican is required for neutrophil extravasation following corneal injury and
      wound healing.
AB  - An important aspect of wound healing is the recruitment of neutrophils to the
      site of infection or tissue injury. Lumican, an extracellular matrix component
      belonging to the small leucine rich proteoglycan (SLRP) family, is one of the
      major keratan sulfate proteoglycans (KSPGs) within the corneal stroma. Increasing
      evidence indicates that lumican can serve as a regulatory molecule for several
      cellular processes, including cell proliferation and migration. In the present
      study, we addressed the role of lumican in the process of extravasation of
      polymorphonuclear leukocytes (PMNs) during the early inflammatory phase present
      in the healing of the corneal epithelium following debridement. We used Lum(-/-)
      mice and a novel transgenic mouse, Lum(-/-),Kera-Lum, which expresses lumican
      only in the corneal stroma, to assess the role of lumican in PMN extravasation
      into injured corneas. Our results showed that PMNs did not readily invade injured
      corneas of Lum(-/-) mice and this defect was rescued by the expression of lumican
      in the corneas of Lum(-/-),Kera-Lum mice. The presence of lumican in situ
      facilitates PMN infiltration into the peritoneal cavity in casein-induced
      inflammation. Our findings are consistent with the notion that in addition to
      regulating the collagen fibril architecture, lumican acts to aid neutrophil
      recruitment and invasion following corneal damage and inflammation.

PMID- 20699361
TI  - Role of CD27/CD70 pathway of activation in immunity and tolerance.
AB  - The CD70/CD27 axis has gained increasing interest among the immunologists,
      because of its capacity to regulate immunity versus tolerance. Recent studies
      clearly show that expression of CD70 may prevent tolerance induced by antigen
      presentation in the steady-state, i.e., by nonactivated DCs. In addition, CD27
      signaling appears critical for T cell expansion and survival and therefore,
      induction of long-term memory. It contributes to germinal center formation, B
      cell activation, and production of neutralizing antibodies but can also be
      subverted by viruses, in particular, during chronic infections. The potential
      role of the CD27/CD70 pathway in the course of inflammatory diseases, as in EAE,
      arthritis, and inflammatory bowel disease models, suggests that CD70 may be a
      target for immune intervention. Conversely, the potency of costimulation through
      CD27 suggests that the CD27/CD70 axis could be exploited for the design of anti
      cancer vaccines.

PMID- 20699363
TI  - Magnetic resonance metabolomics of intact tissue: a biotechnological tool in
      cancer diagnostics and treatment evaluation.
AB  - Personalized medicine is increasingly important in cancer treatment for its role
      in staging and its potential to improve stratification of patients. Different
      types of molecules, genes, proteins, and metabolites are being extensively
      explored as potential biomarkers. This review discusses the major findings and
      potential of tissue metabolites determined by high-resolution magic angle
      spinning magnetic resonance spectroscopy for cancer detection, characterization,
      and treatment monitoring.

PMID- 20699362
TI  - Cholesterol 25-hydroxylase production by dendritic cells and macrophages is
      regulated by type I interferons.
AB  - The oxysterol-producing enzyme CH25H plays an important role in regulating lipid
      metabolism, gene expression, and immune activation. In vitro experiments using a
      panel of TLR agonists to activate BMDCs and macrophages demonstrated that Ch25h
      expression is induced rapidly, selectively, and robustly by the TLR ligands poly
      I:C and LPS. The mechanism of TLR3- and TLR4-induced transcription levels of
      Ch25h relies on the TRIF-mediated production of type I IFNs and requires
      signaling through the IFNalphaR and JAK/STAT1 pathway. Treatment of BMDCs and
      macrophages with IFN-alpha or IFN-beta induces Ch25h in a STAT1-dependent manner.
      IFN-gamma also up-regulated Ch25h expression by signaling through STAT1,
      suggesting that multiple pathways regulate the production of this enzyme. In
      addition, we demonstrated that regulation of Ch25h expression in vivo in lung
      derived DCs and macrophages is dependent on signaling through the IFNalphaR and
      STAT1. The results suggest that the rapid induction of Ch25h and subsequent
      oxysterol synthesis may represent a component of the regulatory network that
      modulates the magnitude of innate immune reactions and possibly the nature and
      intensity of subsequent adaptive responses.

PMID- 20699364
TI  - Matrix metalloproteinase-9 is upregulated in nucleophosmin-anaplastic lymphoma
      kinase-positive anaplastic lymphomas and activated at the cell surface by the
      chaperone heat shock protein 90 to promote cell invasion.
AB  - Many anaplastic large cell lymphomas (ALCL) express the chimeric oncogene NPM
      ALK, which drives malignant transformation and invasion. In this study, we show
      that NPM-ALK expression increases matrix metalloproteinase-9 (MMP-9) expression.
      Accordingly, we found that 100% of a large panel of ALK(+) ALCL biopsies examined
      were also MMP-9(+), in contrast to only 36.3% of ALK(-) tumors. Mechanistic
      studies revealed that Rac1 drove MMP-9 secretion. The MMP inhibitor GM6001 and
      MMP-9 blocking antibodies abolished the invasiveness of NPM-ALK(+) cells.
      Interestingly, the hyaluronan receptor CD44 acted as a docking surface for MMP-9
      and the chaperone heat shock protein 90 on the cell surface, where MMP-9 was
      cleaved and activated. Membrane-associated MMP-9 was localized to invadopodia,
      which display a strong gelatinase activity. Taken together, our observations
      strengthen the concept that chaperones have a major extracellular role in the
      regulation of protein activation status, and reveal new factors that are crucial
      for spreading and invasion of ALK(+) ALCL. They also point out new factors
      crucial for ALK(+) ALCL.

PMID- 20699366
TI  - Suppression of casein kinase 1alpha in melanoma cells induces a switch in beta
      catenin signaling to promote metastasis.
AB  - Casein kinase 1 alpha (CK1alpha) is a multifunctional Ser/Thr kinase that
      phosphorylates several substrates. Among those is beta-catenin, an important
      player in cell adhesion and Wnt signaling. Phosphorylation of beta-catenin by
      CK1alpha at Ser45 is the priming reaction for the proteasomal degradation of beta
      catenin. Interestingly, aside from this role in beta-catenin degradation, very
      little is known about the expression and functional role of CK1alpha in tumor
      cells. Here, we show that CK1alpha expression in different tumor types is either
      strongly suppressed or completely lost during tumor progression and that CK1alpha
      is a key factor determining beta-catenin stability and transcriptional activity
      in tumor cells. CK1alpha reexpression in metastatic melanoma cells reduces growth
      in vitro and metastasis formation in vivo, and induces cell cycle arrest and
      apoptosis, whereas suppression of CK1alpha in primary melanoma cells induces
      invasive tumor growth. Inactivation of CK1alpha promotes tumor progression by
      regulating a switch in beta-catenin-mediated signaling. These results show that
      melanoma cells developed an efficient new mechanism to activate the beta-catenin
      signaling pathway and define CK1alpha as a novel tumor suppressor.

PMID- 20699365
TI  - PIK3CA mutation uncouples tumor growth and cyclin D1 regulation from MEK/ERK and
      mutant KRAS signaling.
AB  - Mutational activation of KRAS is a common event in human tumors. Identification
      of the key signaling pathways downstream of mutant KRAS is essential for our
      understanding of how to pharmacologically target these cancers in patients. We
      show that PD0325901, a small-molecule MEK inhibitor, decreases MEK/ERK pathway
      signaling and destabilizes cyclin D1, resulting in significant anticancer
      activity in a subset of KRAS mutant tumors in vitro and in vivo. Mutational
      activation of PIK3CA, which commonly co-occurs with KRAS mutation, provides
      resistance to MEK inhibition through reactivation of AKT signaling. Genetic
      ablation of the mutant PIK3CA allele in MEK inhibitor-resistant cells restores
      MEK pathway sensitivity, and re-expression of mutant PIK3CA reinstates the
      resistance, highlighting the importance of this mutation in resistance to therapy
      in human cancers. In KRAS mutant tumors, PIK3CA mutation restores cyclin D1
      expression and G(1)-S cell cycle progression so that they are no longer dependent
      on KRAS and MEK/ERK signaling. Furthermore, the growth of KRAS mutant tumors with
      coexistent PIK3CA mutations in vivo is profoundly inhibited with combined
      pharmacologic inhibition of MEK and AKT. These data suggest that tumors with both
      KRAS and phosphoinositide 3-kinase mutations are unlikely to respond to the
      inhibition of the MEK pathway alone but will require effective inhibition of both
      MEK and phosphoinositide 3-kinase/AKT pathway signaling.

PMID- 20699367
TI  - Insulin receptor A and IGF-1R in AML - Letter.

PMID- 20699369
TI  - Reciprocal activation of prostate cancer cells and cancer-associated fibroblasts
      stimulates epithelial-mesenchymal transition and cancer stemness.
AB  - Although cancer-associated fibroblasts (CAF) are key determinants in the
      malignant progression of cancer, their functional contribution to this process is
      still unclear. Analysis of the mutual interplay between prostate carcinoma cells
      and CAFs revealed a mandatory role of carcinoma-derived interleukin-6 in
      fibroblast activation. In turn, activated fibroblasts through secretion of
      metalloproteinases elicit in cancer cells a clear epithelial-mesenchymal
      transition (EMT), as well as enhancement of tumor growth and development of
      spontaneous metastases. CAF-induced EMT leads prostate carcinoma cells to enhance
      expression of stem cell markers, as well as the ability to form prostaspheres and
      to self-renew. Hence, the paracrine interplay between CAFs and cancer cells leads
      to an EMT-driven gain of cancer stem cell properties associated with
      aggressiveness and metastatic spread.

PMID- 20699370
TI  - CDX2 regulates multidrug resistance 1 gene expression in malignant intestinal
      epithelium.
AB  - The caudal-related homeobox transcription factor CDX2 has a key role in
      intestinal development and differentiation. CDX2 heterozygous mutant mice develop
      colonic polyps, and loss of CDX2 expression is seen in a subset of colon
      carcinomas in humans. Ectopic CDX2 expression in the stomach of transgenic mice
      promotes intestinal metaplasia, and CDX2 expression is frequently detected in
      intestinal metaplasia in the stomach and esophagus. We sought to define CDX2
      regulated genes to enhance knowledge of CDX2 function. HT-29 colorectal cancer
      cells have minimal endogenous CDX2 expression, and HT-29 cells with ectopic CDX2
      expression were generated. Microarray-based gene expression studies revealed that
      the Multidrug Resistance 1 (MDR1/P-glycoprotein/ABCB1) gene was activated by
      CDX2. Evidence that the MDR1 gene was a direct transcriptional target of CDX2 was
      obtained, including analyses with MDR1 reporter gene constructs and chromatin
      immunoprecipitation assays. RNA interference-mediated inhibition of CDX2
      decreased endogenous MDR1 expression. In various colorectal cancer cell lines and
      human tissues, endogenous MDR1 expression was well correlated to CDX2 expression.
      Overexpression of CDX2 in HT-29 cells revealed increased resistance to the known
      substrate of MDR1, vincristine and paclitaxel, which was reversed by an MDR1
      inhibitor, verapamil. These data indicate that CDX2 directly regulates MDR1 gene
      expression through binding to elements in the promoter region. Thus, CDX2 is
      probably important for basal expression of MDR1, regulating drug excretion and
      absorption in the lower gastrointestinal tract, as well as for multidrug
      resistance to chemotherapy reagent in CDX2-positive gastrointestinal cancers.

PMID- 20699371
TI  - Serum IGF-I, IGF-II, IGFBP-3, and IGF-I/IGFBP-3 molar ratio and risk of
      pancreatic cancer in the prostate, lung, colorectal, and ovarian cancer screening
      trial.
AB  - BACKGROUND: Experimental evidence suggests that an overexpression of insulin-like
      growth factor (IGF)-I is implicated in human pancreatic tumors. Increased IGF-II
      and decreased IGF binding protein (IGFBP)-3 serum concentrations have been linked
      to a number of other cancers. METHODS: We conducted a nested case-control study
      in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial cohort of
      men and women 55 to 74 years of age at baseline to test whether prediagnostic
      circulating IGF-I, IGF-II, IGFBP-3, and IGF-I/IGFBP-3 molar ratio concentrations
      were associated with exocrine pancreatic cancer risk. Between 1994 and 2006, 187
      incident cases of pancreatic adenocarcinoma occurred (follow-up of up to 11.7
      years). Two controls (n = 374), who were alive at the time the case was
      diagnosed, were selected for each case and matched by age, race, sex, and date of
      blood draw. We calculated odds ratios (OR) and 95% confidence intervals (95% CI)
      with the use of conditional logistic regression, adjusting for smoking. RESULTS:
      IGF-I, IGF-II, and IGFBP-3 concentrations were not significantly associated with
      pancreatic cancer (highest compared with lowest quartile: OR, 1.58; 95% CI, 0.91
      2.76; and P-trend = 0.25; OR, 0.86; 95% CI, 0.49-1.50; and P-trend = 0.31; and
      OR, 0.88; 95% CI, 0.51-1.51; and P-trend = 0.47, respectively). However, a
      significant positive trend was observed with high IGF-I/IGFBP-3 molar ratio
      levels (highest compared with lowest quartile: OR, 1.54; 95% CI, 0.89-2.66; P
      trend = 0.04). CONCLUSION: A higher IGF-I/IGFBP-3 molar ratio represents
      increased free IGF-I, which may be a risk factor for pancreatic cancer. IMPACT:
      Our results highlight the importance of this biomarker for further investigation
      in large prospective cohort studies and pooled analysis with other prospective
      cohorts.

PMID- 20699372
TI  - Alcohol and tobacco use in relation to gastric cancer: a prospective study of men
      in Shanghai, China.
AB  - BACKGROUND: Epidemiologic findings of tobacco and alcohol use in relation to
      gastric cancer are inconsistent. Well-designed prospective studies examining
      their relationship are sparse. METHODS: The association between cigarette
      smoking/alcohol intake and gastric cancer risk was examined in a population-based
      prospective cohort of 18,244 middle-aged and older men in Shanghai, China, who
      were enrolled in the study during 1986-1989. After up to 20 years of follow-up,
      391 incident gastric cancer cases were identified. Cox proportional hazards
      regression models were used to estimate hazard ratios (HR) and corresponding 95%
      confidence intervals (95% CI). RESULTS: Ever smokers experienced a statistically
      significant increased risk of gastric cancer (HR, 1.59; 95% CI, 1.27-1.99)
      compared with nonsmokers after adjustment for alcohol intake and other
      confounders. Among nondrinkers, smokers experienced 80% increased risk of gastric
      cancer (HR, 1.81; 95% CI,1.36, 2.41). Conversely, heavy drinkers experienced a
      statistically significant increase in risk of gastric cancer (HR, 1.46; 95% CI,
      1.05-2.04) among all subjects and a statistically nonsignificant 80% increased
      risk among never smokers. Further adjustment for Helicobacter pylori serology,
      serum levels of beta-carotene and vitamin C, and urinary level of total
      isothiocyanates in combination with glutathione S-transferase (GST) M1 and GSTT1
      genotypes did not materially change the associations between smoking/alcohol
      consumption and gastric cancer risk. CONCLUSIONS: These results suggest that
      cigarette smoking and alcohol consumption may exert independent effects on the
      development of gastric cancer in this high-risk population. IMPACT: Modification
      of these lifestyle choices may reduce the incidence of gastric cancer.

PMID- 20699373
TI  - Knowledge and use of finasteride for the prevention of prostate cancer.
AB  - BACKGROUND: The knowledge about and use of chemopreventive agents for prostate
      cancer by physicians has not been described. The Prostate Cancer Prevention Trial
      (PCPT) showed that finasteride was effective in reducing the incidence of
      prostate cancer. We examined the influence of the PCPT on finasteride prescribing
      within the Veterans Health Administration (VHA). METHODS: We assessed trends on
      monthly new and total prescriptions for finasteride filled within the VHA from
      January 2000 to December 2005. Additionally, all VHA urologists and a random
      sample of VHA primary care physicians (PCP) were surveyed about their use of
      finasteride. RESULTS: The number of men starting finasteride grew over the study
      period. Publication of the PCPT was not significantly associated with any change
      in this pattern (P = 0.45). Fifty-seven percent of urologists and 40% of PCPs
      endorsed prescribing finasteride more frequently in 2006 than 5 years prior.
      However, among those who reported changing prescribing patterns, fewer than 2%
      reported being influenced by the PCPT. Sixty-four percent of urologists and 80%
      of PCPs never prescribe finasteride for prostate cancer chemoprevention; 55% of
      urologists cited concerns of inducing high-grade tumors, whereas 52% of PCPs did
      not know it could be used for chemoprevention. CONCLUSIONS: The number of men
      starting finasteride in the VHA increased over time, but the change did not seem
      to be due to increased use of finasteride for chemoprevention. Publication of the
      PCPT seemed to have little influence over the study period. IMPACT: Physicians
      may not readily accept the use of chemopreventive agents for prostate cancer.

PMID- 20699374
TI  - Evaluation of breast cancer susceptibility loci in Chinese women.
AB  - BACKGROUND: Recent genome-wide association studies (GWAS), mostly conducted among
      women of European ancestry, have identified 16 single-nucleotide polymorphisms
      (SNP) associated with breast cancer. METHODS: We evaluated these SNPs with the
      risk of breast cancer and further by estrogen receptor status in a population
      based study of 6,498 cases and 3,999 controls in Chinese women. We also searched
      for novel genetic risk variants in four loci, 2q35, 5p12/MRPS30, 8q24.21, and
      17q23.2/COX11, in a two-stage study. In stage I, 868 SNPs were analyzed in 2,073
      cases and 2,084 controls. In stage II, 58 SNPs selected from stage I were
      evaluated, including 4,425 cases and 1,915 controls. RESULTS: Statistically
      significant associations (P < 0.05) were observed for eight GWAS-identified SNPs,
      including rs4973768 (3p24/SLC4A7), rs889312 (5q11.2MAP3K1), rs2046210 (6q25.1),
      rs1219648 (10q26.13/FGFR2), rs2981582 (10q26.13/FGFR2), rs3817198 (11p15.5/LSP1),
      rs8051542 (16q12.1/TOX3), and rs3803662 (16q12.1/TOX3). Two additional SNPs,
      rs10941679 (5p12/MRPS30) and rs13281615 (8q24.21), showed a marginally
      significant association. Some of these associations varied by estrogen receptor
      status. In the fine-mapping analysis, five SNPs showed a consistent association
      with breast cancer risk in both stages: rs10169372 (2q35), rs283720 (8q24.21),
      rs10515083 (17q23.2/COX11), rs16955329 (17q23.2/COX11), and rs2787487
      (17q23.2/COX11). CONCLUSIONS: This study shows that approximately half of the
      SNPs initially reported from GWAS of breast cancer in European descendants can be
      directly replicated in Chinese. Our fine-mapping analyses revealed several
      candidates of risk variants that can be further evaluated in studies with a
      larger sample size. IMPACT: Findings from this study may help guide future fine
      mapping studies to identify causal variants for breast cancer.

PMID- 20699375
TI  - Communication of BRCA results and family testing in 1,103 high-risk women.
AB  - BACKGROUND: Genetic testing for hereditary cancer risk has implications for
      individuals and families. This study of women at risk of hereditary breast and
      ovarian cancer examines communication of BRCA results and subsequent genetic
      testing in the family. METHODS: We surveyed 1,103 female BRCA testers at two
      hospitals, querying for communication of results and testing in relatives.
      RESULTS: Ninety-seven percent of participants communicated BRCA results with at
      least one relative. Communication was negatively associated with older age [odds
      ratio (OR), 0.66 per decade; 95% confidence interval, (95% CI), 0.4-0.9], Asian
      race (OR, 0.18; 95% CI, 0.06-0.5), and testing at the public hospital versus the
      cancer center (OR, 0.19; 95% CI, 0.07-0.5). Communication was positively
      associated with increased knowledge of hereditary breast and ovarian cancer
      screening and risk reduction recommendations (OR, 1.9; 95% CI, 1.1-3.4) and
      increased satisfaction with the decision to BRCA test (OR, 2.6; 95% CI, 1.6-4.0).
      Seventy-five percent of BRCA-positive participants reported that at least one
      relative pursued genetic testing. Family testing was negatively associated with
      Asian race (OR, 0.15; 95% CI, 0.02-0.8) and positively associated with increased
      socioeconomic status (OR, 1.4; 95% CI, 1.1-1.7) and increased satisfaction with
      decision (OR, 2.1; 95% CI, 1.1-4.1). CONCLUSION: Despite high overall rates of
      communicating BRCA results, underserved and some minority women seem less likely
      to inform relatives of their BRCA status or have relatives test for a known
      family mutation. Satisfaction with the decision to BRCA test is positively
      associated with both outcomes. IMPACT: This study identified several novel
      predictors of family communication and family genetic testing in a large
      population of high-risk women. This work can inform clinicians interested in
      improving family communication regarding cancer predisposition testing.

PMID- 20699376
TI  - Rapid mass spectrometric metabolic profiling of blood sera detects ovarian cancer
      with high accuracy.
AB  - BACKGROUND: Ovarian cancer diagnosis is problematic because the disease is
      typically asymptomatic, especially at the early stages of progression and/or
      recurrence. We report here the integration of a new mass spectrometric technology
      with a novel support vector machine computational method for use in cancer
      diagnostics, and describe the application of the method to ovarian cancer.
      METHODS: We coupled a high-throughput ambient ionization technique for mass
      spectrometry (direct analysis in real-time mass spectrometry) to profile relative
      metabolite levels in sera from 44 women diagnosed with serous papillary ovarian
      cancer (stages I-IV) and 50 healthy women or women with benign conditions. The
      profiles were input to a customized functional support vector machine-based
      machine-learning algorithm for diagnostic classification. Performance was
      evaluated through a 64-30 split validation test and with a stringent series of
      leave-one-out cross-validations. RESULTS: The assay distinguished between the
      cancer and control groups with an unprecedented 99% to 100% accuracy (100%
      sensitivity and 100% specificity by the 64-30 split validation test; 100%
      sensitivity and 98% specificity by leave-one-out cross-validations). CONCLUSION:
      The method has significant clinical potential as a cancer diagnostic tool.
      Because of the extremely low prevalence of ovarian cancer in the general
      population (approximately 0.04%), extensive prospective testing will be required
      to evaluate the test's potential utility in general screening applications.
      However, more immediate applications might be as a diagnostic tool in higher-risk
      groups or to monitor cancer recurrence after therapeutic treatment. IMPACT: The
      ability to accurately and inexpensively diagnose ovarian cancer will have a
      significant positive effect on ovarian cancer treatment and outcome.

PMID- 20699377
TI  - Menopausal hormone therapy and subsequent risk of specific invasive breast cancer
      subtypes in the California Teachers Study.
AB  - BACKGROUND: Although it is well established that combined estrogen-progestin
      therapy (EPT) increases breast cancer risk, questions remain regarding the effect
      of different formulations of hormones, whether certain women are at particularly
      high risk, and whether risk varies by tumor subtype. METHODS: We investigated
      hormone therapy (HT) use in relation to breast cancer risk in the California
      Teachers Study cohort; after a mean follow-up of 9.8 years, 2,857 invasive breast
      cancers were diagnosed. RESULTS: Compared with women who had never used HT, women
      who reported 15 or more years of estrogen therapy (ET) use had a 19% greater risk
      of breast cancer (95% confidence interval, 1.03-1.37), whereas women using EPT
      for 15 or more years had an 83% greater risk (95% confidence interval, 1.48
      2.26). Breast cancer risk was highest among women using continuous combined EPT
      regimens. Risks associated with EPT and ET use were increased with duration of HT
      use for women with a body mass index (BMI) of <29.9 kg/m(2) but not for women
      with BMI of >or=30 kg/m(2). Elevated risks associated with EPT and ET use were
      confined to tumors that were positive for both estrogen and progesterone
      receptors and those that were HER2+ but were slightly diminished for HER2-
      tumors. CONCLUSIONS: Breast cancer risks increased with longer duration of ET and
      EPT use, and risks were highest for continuous-combined EPT use. Furthermore,
      risks varied by BMI and tumor subtype. IMPACT: These findings underscore the need
      for personalized risk-benefit discussions with women contemplating HT use.

PMID- 20699378
TI  - Comparison study on the complete sequence of hepatitis B virus identifies new
      mutations in core gene associated with hepatocellular carcinoma.
AB  - BACKGROUND: Mutations in the hepatitis B virus (HBV) genome may influence the
      activity of liver disease. The aim of this study was to identify new viral
      variations associated with hepatocellular carcinoma (HCC). METHODS: We carried
      out a comparison study on the complete sequence of HBV isolated from 20 HCC and
      35 non-HCC patients in Qidong, China, an area with a high incidence of HCC. We
      compared the HBV sequences in a consecutive series of plasma samples from four
      HCC cases before and after the occurrence of HCC. In addition, we selected four
      mutations in the HBV core (C) gene to verify their relationships to HCC in an
      independent set of 103 HCC cases and 103 sex- and age-matched non-HCC controls.
      RESULTS: The pre-S deletion and 12 point mutations, namely, the pre-S2 start
      codon mutation, T53C in the pre-S2 gene, T766A in the S gene, G1613A, C1653T,
      A1762T, G1764A in the X gene, and G1899A, C2002T, A2159G, A2189C, and G2203W (A
      or T) in the pre-C/C gene, showed close associations with HCC. In the validation
      study, A2159G, A2189C, and G2203W showed consistent associations with HCC by
      univariate analysis. Multivariate analysis showed that A2189C and G2203W were
      independent risk factors for HCC. The odds ratios (95% confidence interval) were
      3.99 (1.61-9.92) and 9.70 (1.17-80.58), respectively, for A2189C and G2203W.
      CONCLUSIONS: These results implicate A2189C and G2203W as new predictive markers
      for HCC. IMPACT: The complete genome analysis of HBV provided pilot data for the
      identification of novel mutations that could serve as markers for HCC.

PMID- 20699379
TI  - Expression of the tumor suppressor Kruppel-like factor 4 as a prognostic
      predictor for colon cancer.
AB  - BACKGROUND: The zinc finger transcription factor Kruppel-like factor 4 (KLF4)
      regulates numerous physiologic processes, including proliferation,
      differentiation, and development. Studies also showed that KLF4 is involved in
      tumorigenesis and somatic cell reprogramming. Here, we aimed to assess whether
      KLF4 is a prognostic indicator for colon cancer. METHODS: Levels of KLF4 were
      measured by immunohistochemical analysis of a tissue microarray containing 367
      independent colon cancer sections. Univariate data analysis was done in addition
      to construction of multivariate models with several clinicopathologic factors to
      evaluate KLF4 as an independent predictor of survival and cancer recurrence
      (disease-free survival). RESULTS: Colon cancer tissues had significantly overall
      lower KLF4 levels compared with noncancer tissues (P < 0.0001). Using logistic
      regression, a trend was noted for decreased odds of KLF4 expression in higher
      stages of tumors. In univariate and multivariate analyses, KLF4 was a significant
      predictor of survival and recurrence. CONCLUSIONS: KLF4 expression is
      significantly downregulated in colon cancer, and loss of KLF4 is an independent
      predictor of survival and recurrence. IMPACT: These findings suggest that KLF4
      may serve as a prognostic biomarker for colon cancer.

PMID- 20699380
TI  - Evidence that high variation in antral follicle count during follicular waves is
      linked to alterations in ovarian androgen production in cattle.
AB  - Androgens have an important role in ovarian follicular growth and function, but
      circulating androgen concentrations are also associated with ovarian dysfunction,
      cardiovascular disease, and metabolic disorders in women. The extent and causes
      of the variation in androgen production in individuals, however, are unknown.
      Because thecal cells of follicles synthesize androstenedione and testosterone,
      variation in production of these androgens is hypothesized to be directly related
      to the inherently high variation in number of healthy growing follicles in
      ovaries of individuals. To test this hypothesis, we determined whether thecal
      CYP17A1 mRNA (codes for a cytochrome P450 enzyme involved in androgen synthesis),
      LH-induced thecal androstenedione production, androstenedione concentrations in
      follicular fluid, and circulating testosterone concentrations were lower in
      cattle with relatively low versus high number of follicles growing during
      follicular waves and whether ovariectomy reduced serum testosterone
      concentrations. Results demonstrated that cattle with a low follicle number had
      lower (P<0.05) abundance of CYP17A1 mRNA in thecal cells, reduced (P<0.01)
      capacity of thecal cells to produce androstenedione in response to LH, lower
      (P<0.01) androstenedione concentrations in ovulatory follicles, and lower
      (P<0.02) circulating testosterone concentrations during estrous cycles compared
      with animals with high follicle number. Also, serum testosterone in cattle with
      low or high follicle number was reduced by 63 and 70%, respectively, following
      ovariectomy. In conclusion, circulating androgen concentrations are lower in
      cattle with low versus high number of follicles growing during follicular waves,
      possibly because of a reduced responsiveness of thecal cells to LH.

PMID- 20699381
TI  - A combined proteomics and metabolomics profiling of gastric cardia cancer reveals
      characteristic dysregulations in glucose metabolism.
AB  - Gastric cardia cancer (GCC), which occurs at the gastric-esophageal boundary, is
      one of the most malignant tumors. Despite its high mortality and morbidity, the
      molecular mechanism of initiation and progression of this disease is largely
      unknown. In this study, using proteomics and metabolomics approaches, we found
      that the level of several enzymes and their related metabolic intermediates
      involved in glucose metabolism were deregulated in GCC. Among these enzymes, two
      subunits controlling pyruvic acid efflux, lactate dehydrogenase A (LDHA) and
      pyruvate dehydrogenase B (PDHB), were further analyzed in vitro. Either down
      regulation of LDH subunit LDHA or overexpression of PDH subunit PDHB could force
      pyruvic acid into the Krebs cycle rather than the glycolysis process in AGS
      gastric cancer cells, which inhibited cell growth and cell migration. Our results
      reflect an important glucose metabolic signature, especially the dysregulation of
      pyruvic acid efflux in the development of GCC. Forced transition from glycolysis
      to the Krebs cycle had an inhibitory effect on GCC progression, providing
      potential therapeutic targets for this disease.

PMID- 20699382
TI  - Adrenocortical carcinoma and pregnancy: clinical and biological features and
      prognosis.
AB  - OBJECTIVE: Adrenocortical carcinoma (ACC) is a rare, severe disease. Pregnancy
      associated ACC has rarely been reported. We wished to evaluate the
      characteristics and prognosis of ACC diagnosed in patients during pregnancy or in
      the postpartum period, comparing them with those for ACC diagnosed in nonpregnant
      women. DESIGN: Clinical presentation, hormonal secretion, staging, survival, and
      obstetric data are reported. Patients were included between 1963 and 2007. Mean
      follow-up was 48 months. PATIENTS AND METHODS: This is a retrospective cohort
      study carried out at a referral center. All female patients aged 16-49 years
      diagnosed with ACC during the observation period were included (n=110). Twelve of
      these women were pregnant or in the first 6 months after delivery. Hormonal
      secretion, staging, obstetric data, and survival were analyzed. For the survival
      analysis, pregnant patients were compared with a subgroup of nonpregnant women
      matched for age, stage, and year of diagnosis (1 pregnant patient/2 controls).
      RESULTS: Adrenocortical tumors diagnosed during pregnancy or in the postpartum
      period tend to be more often cortisol-secreting tumors (P=0.06) and to be
      discovered at a more advanced stage than those in nonpregnant women, although the
      differences were not significant. Fetal outcome was poor. Overall survival of the
      mother was worse than that of matched controls (hazard ratio of death: 3.98,
      confidence interval=1.34-11.85, P=0.013). CONCLUSION: ACC diagnosed during
      pregnancy or in the postpartum period is associated with a poor fetal outcome and
      a poorer prognosis than ACC diagnosed in nonpregnant women.

PMID- 20699383
TI  - Influence of pegvisomant on serum ghrelin and leptin levels in acromegalic
      patients.
AB  - INTRODUCTION: Pegvisomant (peg) is a GH receptor antagonist. In de novo
      acromegalic patients with high GH levels, ghrelin and leptin levels are reduced,
      suggesting a direct GH-mediated effect. The aim of our study was to evaluate
      whether peg treatment in acromegalic patients may abolish the GH impact on
      ghrelin and leptin levels. METHODS: Ghrelin, leptin and endogenous GH were
      measured in ten peg-treated acromegalic patients (three females/seven males, 47
      years (28-57)), ten patients with active (act) and ten patients with inactive
      disease (inact) as well as in ten gender-, age- and body mass index (BMI)-matched
      healthy volunteers (controls). Endogenous GH was measured using a special in
      house assay without interference by peg; total ghrelin and leptin were determined
      using a commercial RIA and an immunofluorometric in-house assay respectively.
      RESULTS: Age and BMI did not differ significantly between groups. Endogenous GH
      was significantly higher in peg (6.3 MUg/l (1.5-41)) and act (9.3 MUg/l (1.7-70))
      compared with controls (0.1 MUg/l (0.1-3.1)) and inact (0.35 MUg/l (0.1-2.0),
      P<0.001). Ghrelin was significantly higher in peg (232  ng/l (96-351)) compared
      with act (102 ng/l (33-232), P<0.01), whereas ghrelin was not significantly
      different between the other groups. Leptin was highest in controls (19 MUg/l (4
      57)) and lowest in act (6 MUg/l (2-21)), but this difference did not reach
      significance. CONCLUSION: Treatment with peg seems to disrupt the feedback loop
      of ghrelin and GH, leading to elevated ghrelin levels. Furthermore, peg therapy
      appears not to have a strong impact on leptin levels, as acromegalic patients
      with and without peg treatment showed similar leptin levels.

PMID- 20699384
TI  - Conserved vertebrate mir-451 provides a platform for Dicer-independent, Ago2
      mediated microRNA biogenesis.
AB  - Canonical animal microRNAs (miRNAs) are generated by sequential cleavage of
      precursor substrates by the Drosha and Dicer RNase III enzymes. Several variant
      pathways exploit other RNA metabolic activities to generate functional miRNAs.
      However, all of these pathways culminate in Dicer cleavage, suggesting that this
      is a unifying feature of miRNA biogenesis. Here, we show that maturation of miR
      451, a functional miRNA that is perfectly conserved among vertebrates, is
      independent of Dicer. Instead, structure-function and knockdown studies indicate
      that Drosha generates a short pre-mir-451 hairpin that is directly cleaved by
      Ago2 and followed by resection of its 3' terminus. We provide stringent evidence
      for this model by showing that Dicer knockout cells can generate mature miR-451
      but not other miRNAs, whereas Ago2 knockout cells reconstituted with wild-type
      Ago2, but not Slicer-deficient Ago2, can process miR-451. Finally, we show that
      the mir-451 backbone is amenable to reprogramming, permitting vector-driven
      expression of diverse functional miRNAs in the absence of Dicer. Beyond the
      demonstration of an alternative strategy to direct gene silencing, these
      observations open the way for transgenic rescue of Dicer conditional knockouts.

PMID- 20699385
TI  - Mutagenic potency of Helicobacter pylori in the gastric mucosa of mice is
      determined by sex and duration of infection.
AB  - Helicobacter pylori is a human carcinogen, but the mechanisms evoked in
      carcinogenesis during this chronic inflammatory disease remain incompletely
      characterized. We determined whether chronic H. pylori infection induced
      mutations in the gastric mucosa of male and female gpt delta C57BL/6 mice
      infected for 6 or 12 mo. Point mutations were increased in females infected for
      12 mo. The mutation frequency in this group was 1.6-fold higher than in
      uninfected mice of both sexes (P < 0.05). A:T-to-G:C transitions and G:C-to-T:A
      transversions were 3.8 and 2.0 times, respectively, more frequent in this group
      than in controls. Both mutations are consistent with DNA damage induced by
      oxidative stress. No increase in the frequency of deletions was observed. Females
      had more severe gastric lesions than males at 6 mo postinfection (MPI; P < 0.05),
      but this difference was absent at 12 MPI. In all mice, infection significantly
      increased expression of IFNgamma, IL-17, TNFalpha, and iNOS at 6 and 12 mo, as
      well as H. pylori-specific IgG1 levels at 12 MPI (P < 0.05) and IgG2c levels at 6
      and 12 MPI (P < 0.01 and P < 0.001). At 12 MPI, IgG2c levels in infected females
      were higher than at 6 MPI (P < 0.05) and also than those in infected males at 12
      MPI (P < 0.05). Intensity of responses was mediated by sex and duration of
      infection. Lower H. pylori colonization indicated a more robust host response in
      females than in males. Earlier onset of severe gastric lesions and
      proinflammatory, Th1-biased responses in female C57BL/6 mice may have promoted
      mutagenesis by exposing the stomach to prolonged oxidative stress.

PMID- 20699387
TI  - Targeting the endothelium to prevent diabetes-related atherosclerosis.

PMID- 20699386
TI  - Analysis of proteome dynamics in the mouse brain.
AB  - Advances in systems biology have allowed for global analyses of mRNA and protein
      expression, but large-scale studies of protein dynamics and turnover have not
      been conducted in vivo. Protein turnover is an important metabolic and regulatory
      mechanism in establishing proteome homeostasis, impacting many physiological and
      pathological processes. Here, we have used organism-wide isotopic labeling to
      measure the turnover rates of approximately 2,500 proteins in multiple mouse
      tissues, spanning four orders of magnitude. Through comparison of the brain with
      the liver and blood, we show that within the respective tissues, proteins
      performing similar functions often have similar turnover rates. Proteins in the
      brain have significantly slower turnover (average lifetime of 9.0 d) compared
      with those of the liver (3.0 d) and blood (3.5 d). Within some organelles (such
      as mitochondria), proteins have a narrow range of lifetimes, suggesting a
      synchronized turnover mechanism. Protein subunits within complexes of variable
      composition have a wide range of lifetimes, whereas those within well-defined
      complexes turn over in a coordinated manner. Together, the data represent the
      most comprehensive in vivo analysis of mammalian proteome turnover to date. The
      developed methodology can be adapted to assess in vivo proteome homeostasis in
      any model organism that will tolerate a labeled diet and may be particularly
      useful in the analysis of neurodegenerative diseases in vivo.

PMID- 20699388
TI  - Effects of admission serum urea, glomerular filtration rate, proteinuria and
      diabetes status on 3-month mortality after acute stroke.

PMID- 20699390
TI  - Dysfunction of chromatin assembly factor 1 induces shortening of telomeres and
      loss of 45S rDNA in Arabidopsis thaliana.
AB  - Chromatin Assembly Factor 1 (CAF1) is a three-subunit H3/H4 histone chaperone
      responsible for replication-dependent nucleosome assembly. It is composed of CAC
      1-3 in yeast; p155, p60, and p48 in humans; and FASCIATA1 (FAS1), FAS2, and
      MULTICOPY SUPPRESSOR OF IRA1 in Arabidopsis thaliana. We report that disruption
      of CAF1 function by fas mutations in Arabidopsis results in telomere shortening
      and loss of 45S rDNA, while other repetitive sequences (5S rDNA, centromeric 180
      bp repeat, CACTA, and Athila) are unaffected. Substantial telomere shortening
      occurs immediately after the loss of functional CAF1 and slows down at telomeres
      shortened to median lengths around 1 to 1.5 kb. The 45S rDNA loss is progressive,
      leaving 10 to 15% of the original number of repeats in the 5th generation of
      mutants affecting CAF1, but the level of the 45S rRNA transcripts is not altered
      in these mutants. Increasing severity of the fas phenotype is accompanied by
      accumulation of anaphase bridges, reduced viability, and plant sterility. Our
      results show that appropriate replication-dependent chromatin assembly is
      specifically required for stable maintenance of telomeres and 45S rDNA.

PMID- 20699391
TI  - Network analysis of enzyme activities and metabolite levels and their
      relationship to biomass in a large panel of Arabidopsis accessions.
AB  - Natural genetic diversity provides a powerful resource to investigate how
      networks respond to multiple simultaneous changes. In this work, we profile
      maximum catalytic activities of 37 enzymes from central metabolism and generate a
      matrix to investigate species-wide connectivity between metabolites, enzymes, and
      biomass. Most enzyme activities change in a highly coordinated manner, especially
      those in the Calvin-Benson cycle. Metabolites show coordinated changes in defined
      sectors of metabolism. Little connectivity was observed between maximum enzyme
      activities and metabolites, even after applying multivariate analysis methods.
      Measurements of posttranscriptional regulation will be required to relate these
      two functional levels. Individual enzyme activities correlate only weakly with
      biomass. However, when they are used to estimate protein abundances, and the
      latter are summed and expressed as a fraction of total protein, a significant
      positive correlation to biomass is observed. The correlation is additive to that
      obtained between starch and biomass. Thus, biomass is predicted by two
      independent integrative metabolic biomarkers: preferential investment in
      photosynthetic machinery and optimization of carbon use.

PMID- 20699392
TI  - Phosphatidic acid phosphohydrolase 1 and 2 regulate phospholipid synthesis at the
      endoplasmic reticulum in Arabidopsis.
AB  - Phospholipid biosynthesis is essential for the construction of most eukaryotic
      cell membranes, but how this process is regulated in plants remains poorly
      understood. Here, we show that in Arabidopsis thaliana, two Mg(2+)-dependent
      phosphatidic acid phosphohydrolases called PAH1 and PAH2 act redundantly to
      repress phospholipid biosynthesis at the endoplasmic reticulum (ER). Leaves from
      pah1 pah2 double mutants contain ~1.8-fold more phospholipid than the wild type
      and exhibit gross changes in ER morphology, which are consistent with massive
      membrane overexpansion. The net rate of incorporation of [methyl-(14)C]choline
      into phosphatidylcholine (PC) is ~1.8-fold greater in the double mutant, and the
      transcript abundance of several key genes that encode enzymes involved in
      phospholipid synthesis is increased. In particular, we show that
      PHOSPHORYLETHANOLAMINE N-METHYLTRANSFERASE1 (PEAMT1) is upregulated at the level
      of transcription in pah1 pah2 leaves. PEAMT catalyzes the first committed step of
      choline synthesis in Arabidopsis and defines a variant pathway for PC synthesis
      not found in yeasts or mammals. Our data suggest that PAH1/2 play a regulatory
      role in phospholipid synthesis that is analogous to that described in
      Saccharomyces cerevisiae. However, the target enzymes differ, and key components
      of the signal transduction pathway do not appear to be conserved.

PMID- 20699395
TI  - Finite element model of polar growth in pollen tubes.
AB  - Cellular protuberance formation in walled cells requires the local deformation of
      the wall and its polar expansion. In many cells, protuberance elongation proceeds
      by tip growth, a growth mechanism shared by pollen tubes, root hairs, and fungal
      hyphae. We established a biomechanical model of tip growth in walled cells using
      the finite element technique. We aimed to identify the requirements for spatial
      distribution of mechanical properties in the cell wall that would allow the
      generation of cellular shapes that agree with experimental observations. We based
      our structural model on the parameterized description of a tip-growing cell that
      allows the manipulation of cell size, shape, cell wall thickness, and local
      mechanical properties. The mechanical load was applied in the form of hydrostatic
      pressure. We used two validation methods to compare different simulations based
      on cellular shape and the displacement of surface markers. We compared the
      resulting optimal distribution of cell mechanical properties with the spatial
      distribution of biochemical cell wall components in pollen tubes and found
      remarkable agreement between the gradient in mechanical properties and the
      distribution of deesterified pectin. Use of the finite element method for the
      modeling of nonuniform growth events in walled cells opens future perspectives
      for its application to complex cellular morphogenesis in plants.

PMID- 20699393
TI  - Nonspecific phospholipase C NPC4 promotes responses to abscisic acid and
      tolerance to hyperosmotic stress in Arabidopsis.
AB  - Diacyglycerol (DAG) is an important class of cellular lipid messengers, but its
      function in plants remains elusive. Here, we show that knockout of the
      Arabidopsis thaliana nonspecific phospholipase C (NPC4) results in a decrease in
      DAG levels and compromises plant response to abscisic acid (ABA) and hyperosmotic
      stresses. NPC4 hydrolyzes various phospholipids in a calcium-independent manner,
      producing DAG and a phosphorylated head group. NPC4 knockout (KO) plants display
      decreased ABA sensitivity in seed germination, root elongation, and stomatal
      movement and had decreased tolerance to high salinity and water deficiency.
      Overexpression of NPC4 renders plants more sensitive to ABA and more tolerant to
      hyperosmotic stress than wild-type plants. Addition of a short-chain DAG or a
      short-chain phosphatidic acid (PA) restores the ABA response of NPC4-KO to that
      of the wild type, but the addition of DAG together with a DAG kinase inhibitor
      does not result in a wild-type phenotype. These data suggest that NPC4-produced
      DAG is converted to PA and that NPC4 and its derived lipids positively modulate
      ABA response and promote plant tolerance to drought and salt stresses.

PMID- 20699396
TI  - The glabra1 mutation affects cuticle formation and plant responses to microbes.
AB  - Systemic acquired resistance (SAR) is a form of defense that provides resistance
      against a broad spectrum of pathogens in plants. Previous work indicates a role
      for plastidial glycerolipid biosynthesis in SAR. Specifically, mutations in FATTY
      ACID DESATURASE7 (FAD7), which lead to reduced trienoic fatty acid levels and
      compromised plastidial lipid biosynthesis, have been associated with defective
      SAR. We show that the defective SAR in Arabidopsis (Arabidopsis thaliana) fad7-1
      plants is not associated with a mutation in FAD7 but rather with a second-site
      mutation in GLABRA1 (GL1), a gene well known for its role in trichome formation.
      The compromised SAR in gl1 plants is associated with impairment in their
      cuticles. Furthermore, mutations in two other components of trichome development,
      GL3 and TRANSPARENT TESTA GLABRA1, also impaired cuticle development and SAR.
      This suggests an overlap in the biochemical pathways leading to cuticle and
      trichome development. Interestingly, exogenous application of gibberellic acid
      (GA) not only enhanced SAR in wild-type plants but also restored SAR in gl1
      plants. In contrast to GA, the defense phytohoromes salicylic acid and jasmonic
      acid were unable to restore SAR in gl1 plants. GA application increased levels of
      cuticular components but not trichome formation on gl1 plants, thus implicating
      cuticle, but not trichomes, as an important component of SAR. Our findings
      question the prudence of using mutant backgrounds for genetic screens and
      underscore a need to reevaluate phenotypes previously studied in the gl1
      background.

PMID- 20699397
TI  - The plant-specific SR45 protein negatively regulates glucose and ABA signaling
      during early seedling development in Arabidopsis.
AB  - The plant-specific SR45 belongs to the highly conserved family of serine/arginine
      rich (SR) proteins, which play key roles in precursor-mRNA splicing and other
      aspects of RNA metabolism. An Arabidopsis (Arabidopsis thaliana) loss-of-function
      mutant, sr45-1, displays pleiotropic phenotypes, such as defects in flower and
      leaf morphology, root growth, and flowering time. Here, we show that the sr45-1
      mutation confers hypersensitivity to glucose (Glc) during early seedling growth
      in Arabidopsis. Unlike wild-type plants, the sr45-1 mutant displays impaired
      cotyledon greening and expansion as well as reduced hypocotyl elongation of dark
      grown seedlings when grown in the presence of low (3%) Glc concentrations. In
      addition, SR45 is involved in the control of Glc-responsive gene expression, as
      the mutant displays enhanced repression of photosynthetic and nitrogen metabolism
      genes and overinduction of starch and anthocyanin biosynthesis genes. Like many
      other sugar response mutants, sr45-1 also shows hypersensitivity to abscisic acid
      (ABA) but appears to be unaffected in ethylene signaling. Importantly, the sr45-1
      mutant shows enhanced ability to accumulate ABA in response to Glc, and the ABA
      biosynthesis inhibitor fluridone partially rescues the sugar-mediated growth
      arrest. Moreover, three ABA biosynthesis genes and two key ABA signaling genes,
      ABI3 and ABI5, are markedly overinduced by Glc in sr45-1. These results provide
      evidence that the SR45 protein defines a novel player in plant sugar response
      that negatively regulates Glc signaling during early seedling development by down
      regulating both Glc-specific ABA accumulation and ABA biosynthesis and signaling
      gene expression.

PMID- 20699398
TI  - Nitric oxide acts downstream of auxin to trigger root ferric-chelate reductase
      activity in response to iron deficiency in Arabidopsis.
AB  - In response to iron (Fe) deficiency, dicots employ a reduction-based mechanism by
      inducing ferric-chelate reductase (FCR) at the root plasma membrane to enhance Fe
      uptake. However, the signal pathway leading to FCR induction is still unclear.
      Here, we found that the Fe-deficiency-induced increase of auxin and nitric oxide
      (NO) levels in wild-type Arabidopsis (Arabidopsis thaliana) was accompanied by up
      regulation of root FCR activity and the expression of the basic helix-loop-helix
      transcription factor (FIT) and the ferric reduction oxidase 2 (FRO2) genes. This
      was further stimulated by application of exogenous auxin (alpha-naphthaleneacetic
      acid) or NO donor (S-nitrosoglutathione [GSNO]), but suppressed by either polar
      auxin transport inhibition with 1-naphthylphthalamic acid or NO scavenging with 2
      (4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, tungstate, or
      N(omega)-nitro-L-arginine methyl ester hydrochloride. On the other hand, the root
      FCR activity, NO level, and gene expression of FIT and FRO2 were higher in auxin
      overproducing mutant yucca under Fe deficiency, which were sharply restrained by
      2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide treatment. The
      opposite response was observed in a basipetal auxin transport impaired mutant
      aux1-7, which was slightly rescued by exogenous GSNO application. Furthermore, Fe
      deficiency or alpha-naphthaleneacetic acid application failed to induce Fe
      deficiency responses in noa1 and nial nia2, two mutants with reduced NO
      synthesis, but root FCR activities in both mutants could be significantly
      elevated by GSNO. The inability to induce NO burst and FCR activity was further
      verified in a double mutant yucca noa1 with elevated auxin production and reduced
      NO accumulation. Therefore, we presented a novel signaling pathway where NO acts
      downstream of auxin to activate root FCR activity under Fe deficiency in
      Arabidopsis.

PMID- 20699399
TI  - Evidence that high activity of vacuolar invertase is required for cotton fiber
      and Arabidopsis root elongation through osmotic dependent and independent
      pathways, respectively.
AB  - Vacuolar invertase (VIN) has long been considered as a major player in cell
      expansion. However, direct evidence for this view is lacking due, in part, to the
      complexity of multicellular plant tissues. Here, we used cotton (Gossypium spp.)
      fibers, fast-growing single-celled seed trichomes, to address this issue. VIN
      activity in elongating fibers was approximately 4-6-fold higher than that in
      leaves, stems, and roots. It was undetectable in fiberless cotton seed epidermis
      but became evident in initiating fibers and remained high during their fast
      elongation and dropped when elongation slowed. Furthermore, a genotype with
      faster fiber elongation had significantly higher fiber VIN activity and hexose
      levels than a slow-elongating genotype. By contrast, cell wall or cytoplasmic
      invertase activities did not show correlation with fiber elongation. To unravel
      the molecular basis of VIN-mediated fiber elongation, we cloned GhVIN1, which
      displayed VIN sequence features and localized to the vacuole. Once introduced to
      Arabidopsis (Arabidopsis thaliana), GhVIN1 complemented the short-root phenotype
      of a VIN T-DNA mutant and enhanced the elongation of root cells in the wild type.
      This demonstrates that GhVIN1 functions as VIN in vivo. In cotton fiber, GhVIN1
      expression level matched closely with VIN activity and fiber elongation rate.
      Indeed, transformation of cotton fiber with GhVIN1 RNA interference or
      overexpression constructs reduced or enhanced fiber elongation, respectively.
      Together, these analyses provide evidence on the role of VIN in cotton fiber
      elongation mediated by GhVIN1. Based on the relative contributions of sugars to
      sap osmolality in cotton fiber and Arabidopsis root, we conclude that VIN
      regulates their elongation in an osmotic dependent and independent manner,
      respectively.

PMID- 20699400
TI  - Endogenous abscisic acid as a key switch for natural variation in flooding
      induced shoot elongation.
AB  - Elongation of leaves and stem is a key trait for survival of terrestrial plants
      during shallow but prolonged floods that completely submerge the shoot. However,
      natural floods at different locations vary strongly in duration and depth, and,
      therefore, populations from these locations are subjected to different selection
      pressure, leading to intraspecific variation. Here, we identified the signal
      transduction component that causes response variation in shoot elongation among
      two accessions of the wetland plant Rumex palustris. These accessions differed 2
      fold in petiole elongation rates upon submergence, with fast elongation found in
      a population from a river floodplain and slow elongation in plants from a lake
      bank. Fast petiole elongation under water consumes carbohydrates and depends on
      the (inter)action of the plant hormones ethylene, abscisic acid, and gibberellic
      acid. We found that carbohydrate levels and dynamics in shoots did not differ
      between the fast and slow elongating plants, but that the level of ethylene
      regulated abscisic acid in petioles, and hence gibberellic acid responsiveness of
      these petioles explained the difference in shoot elongation upon submergence.
      Since this is the exact signal transduction level that also explains the
      variation in flooding-induced shoot elongation among plant species (namely, R.
      palustris and Rumex acetosa), we suggest that natural selection results in
      similar modification of regulatory pathways within and between species.

PMID- 20699401
TI  - A gain-of-function mutation in the Arabidopsis disease resistance gene RPP4
      confers sensitivity to low temperature.
AB  - How plants adapt to low temperature is not well understood. To identify
      components involved in low-temperature signaling, we characterized the previously
      isolated chilling-sensitive2 mutant (chs2) of Arabidopsis (Arabidopsis thaliana).
      This mutant grew normally at 22 degrees C but showed phenotypes similar to
      activation of defense responses when shifted to temperatures below 16 degrees C.
      These phenotypes include yellowish and collapsed leaves, increased electrolyte
      leakage, up-regulation of PATHOGENESIS RELATED genes, and accumulation of excess
      hydrogen peroxide and salicylic acid (SA). Moreover, the chs2 mutant was seedling
      lethal when germinated at or shifted for more than 3 d to low temperatures of 4
      degrees C to 12 degrees C. Map-based cloning revealed that a single amino acid
      substitution occurred in the TIR-NB-LRR (for Toll/Interleukin-1 receptor-
      nucleotide-binding Leucine-rich repeat)-type resistance (R) protein RPP4 (for
      Recognition of Peronospora parasitica4), which causes a deregulation of the R
      protein in a temperature-dependent manner. The chs2 mutation led to an increase
      in the mutated RPP4 mRNA transcript, activation of defense responses, and an
      induction of cell death at low temperatures. In addition, a chs2 intragenic
      suppressor, in which the mutation occurs in the conserved NB domain, abolished
      defense responses at lower temperatures. Genetic analyses of chs2 in combination
      with known SA pathway and immune signaling mutants indicate that the chs2
      conferred temperature sensitivity requires ENHANCED DISEASE SUSCEPTIBILITY1,
      REQUIRED FOR Mla12 RESISTANCE, and SUPPRESSOR OF G2 ALLELE OF skp1 but does not
      require PHYTOALEXIN DEFICIENT4, NONEXPRESSOR OF PR GENES1, or SA. This study
      reveals that an activated TIR-NB-LRR protein has a large impact on temperature
      sensitivity in plant growth and survival.

PMID- 20699402
TI  - Leaf senescence signaling: the Ca2+-conducting Arabidopsis cyclic nucleotide
      gated channel2 acts through nitric oxide to repress senescence programming.
AB  - Ca(2+) and nitric oxide (NO) are essential components involved in plant
      senescence signaling cascades. In other signaling pathways, NO generation can be
      dependent on cytosolic Ca(2+). The Arabidopsis (Arabidopsis thaliana) mutant dnd1
      lacks a plasma membrane-localized cation channel (CNGC2). We recently
      demonstrated that this channel affects plant response to pathogens through a
      signaling cascade involving Ca(2+) modulation of NO generation; the pathogen
      response phenotype of dnd1 can be complemented by application of a NO donor. At
      present, the interrelationship between Ca(2+) and NO generation in plant cells
      during leaf senescence remains unclear. Here, we use dnd1 plants to present
      genetic evidence consistent with the hypothesis that Ca(2+) uptake and NO
      production play pivotal roles in plant leaf senescence. Leaf Ca(2+) accumulation
      is reduced in dnd1 leaves compared to the wild type. Early senescence-associated
      phenotypes (such as loss of chlorophyll, expression level of senescence
      associated genes, H(2)O(2) generation, lipid peroxidation, tissue necrosis, and
      increased salicylic acid levels) were more prominent in dnd1 leaves compared to
      the wild type. Application of a Ca(2+) channel blocker hastened senescence of
      detached wild-type leaves maintained in the dark, increasing the rate of
      chlorophyll loss, expression of a senescence-associated gene, and lipid
      peroxidation. Pharmacological manipulation of Ca(2+) signaling provides evidence
      consistent with genetic studies of the relationship between Ca(2+) signaling and
      senescence with the dnd1 mutant. Basal levels of NO in dnd1 leaf tissue were
      lower than that in leaves of wild-type plants. Application of a NO donor
      effectively rescues many dnd1 senescence-related phenotypes. Our work
      demonstrates that the CNGC2 channel is involved in Ca(2+) uptake during plant
      development beyond its role in pathogen defense response signaling. Work
      presented here suggests that this function of CNGC2 may impact downstream basal
      NO production in addition to its role (also linked to NO signaling) in pathogen
      defense responses and that this NO generation acts as a negative regulator during
      plant leaf senescence signaling.

PMID- 20699403
TI  - The microRNA159-regulated GAMYB-like genes inhibit growth and promote programmed
      cell death in Arabidopsis.
AB  - The microRNA159 (miR159) family represses the conserved GAMYB-like genes that
      encode R2R3 MYB domain transcription factors that have been implicated in
      gibberellin (GA) signaling in anthers and germinating seeds. In Arabidopsis
      (Arabidopsis thaliana), the two major miR159 family members, miR159a and miR159b,
      are functionally specific for two GAMYB-like genes, MYB33 and MYB65. These
      transcription factors have been shown to be involved in anther development, but
      there are differing reports about their role in the promotion of flowering and
      little is known about their function in seed germination. To understand the
      function of this pathway, we identified the genes and processes controlled by
      these GAMYB-like genes. First, we demonstrate that miR159 completely represses
      MYB33 and MYB65 in vegetative tissues. We show that GA does not release this
      repression and that these transcription factors are not required for flowering or
      growth. By contrast, in the absence of miR159, the deregulation of MYB33 and
      MYB65 in vegetative tissues up-regulates genes that are highly expressed in the
      aleurone and GA induced during seed germination. Confirming that these genes are
      GAMYB-like regulated, their expression was reduced in myb33.myb65.myb101 seeds.
      Aleurone vacuolation, a GA-mediated programmed cell death process required for
      germination, was impaired in these seeds. Finally, the deregulation of MYB33 and
      MYB65 in vegetative tissues inhibits growth by reducing cell proliferation.
      Therefore, we conclude that miR159 acts as a molecular switch, only permitting
      the expression of GAMYB-like genes in anthers and seeds. In seeds, these
      transcription factors participate in GA-induced pathways required for aleurone
      development and death.

PMID- 20699405
TI  - When values and attributions collide: liberals' and conservatives' values
      motivate attributions for alleged misdeeds.
AB  - Conservatives tend to make dispositional whereas liberals make situational
      attributions for social problems and alleged misconduct (the "ideo-attribution
      effect"). Three studies demonstrated a reversal of the ideo-attribution effect.
      Conservatives made stronger situational attributions than liberals for the
      behavior of Marines accused of killing Iraqi civilians (Studies 1 and 2) and
      police officers accused of wrongly killing a cougar running loose in a Chicago
      neighborhood (Study 3). Reversals of the ideo-attribution effect occurred because
      conservative values were more consistent with excusing the Marines' and police
      officers' behavior, whereas liberal values were more consistent with blaming the
      Marines and police officers. These results suggest that the ideo-attribution
      effect-and attributions more generally-are shaped by whether people's
      attributional conclusions are consistent or inconsistent with their salient
      values.

PMID- 20699404
TI  - A suite of Lotus japonicus starch mutants reveals both conserved and novel
      features of starch metabolism.
AB  - The metabolism of starch is of central importance for many aspects of plant
      growth and development. Information on leaf starch metabolism other than in
      Arabidopsis (Arabidopsis thaliana) is scarce. Furthermore, its importance in
      several agronomically important traits exemplified by legumes remains to be
      investigated. To address this issue, we have provided detailed information on the
      genes involved in starch metabolism in Lotus japonicus and have characterized a
      comprehensive collection of forward and TILLING (for Targeting Induced Local
      Lesions IN Genomes) reverse genetics mutants affecting five enzymes of starch
      synthesis and two enzymes of starch degradation. The mutants provide new insights
      into the structure-function relationships of ADP-glucose pyrophosphorylase and
      glucan, water dikinase1 in particular. Analyses of the mutant phenotypes indicate
      that the pathways of leaf starch metabolism in L. japonicus and Arabidopsis are
      largely conserved. However, the importance of these pathways for plant growth and
      development differs substantially between the two species. Whereas essentially
      starchless Arabidopsis plants lacking plastidial phosphoglucomutase grow slowly
      relative to wild-type plants, the equivalent mutant of L. japonicus grows
      normally even in a 12-h photoperiod. In contrast, the loss of GLUCAN, WATER
      DIKINASE1, required for starch degradation, has a far greater effect on plant
      growth and fertility in L. japonicus than in Arabidopsis. Moreover, we have also
      identified several mutants likely to be affected in new components or regulators
      of the pathways of starch metabolism. This suite of mutants provides a
      substantial new resource for further investigations of the partitioning of carbon
      and its importance for symbiotic nitrogen fixation, legume seed development, and
      perenniality and vegetative regrowth.

PMID- 20699406
TI  - Ingroup identification and group-level narcissism as predictors of U.S. citizens'
      attitudes and behavior toward Arab immigrants.
AB  - In four studies, the authors explored factors contributing to negative attitudes
      and behavior toward Arab immigrants in the United States. In Study 1, Americans
      reported greater threat from Arabs, compared to other groups (e.g., Latino,
      Asian). In Study 2, they tested the effects of ingroup identification and group
      level narcissism on attitudes toward Arab, Latino, Asian, and European
      immigrants. Identification interacted with group narcissism in predicting
      attitudes toward Arab (but not other) immigrants, such that identification
      predicted negative attitudes toward Arab immigrants only at mean and high levels
      of group narcissism. Study 3 explored the convergent and discriminant validity of
      the group narcissism construct. In Study 4, the authors added a behavioral
      dependent measure. Again, ingroup identification predicted negative behavior and
      attitudes toward an Arab immigrant group (but not comparison groups) only at mean
      and high levels of group narcissism. Theoretical and practical implications are
      discussed.

PMID- 20699407
TI  - A single botulinum toxin injection at a precise anatomic point on the forearm
      reduces pain at rest, compared to placebo injection in patients with chronic
      refractory lateral epicondylitis.

PMID- 20699408
TI  - Reduction of N-hydroxy-sulfonamides, including N-hydroxy-valdecoxib, by the
      molybdenum-containing enzyme mARC.
AB  - Purification of the mitochondrial enzyme responsible for reduction of N
      hydroxylated amidine prodrugs led to the identification of two newly discovered
      mammalian molybdenum-containing proteins, the mitochondrial amidoxime reducing
      components mARC-1 and mARC-2 (Gruenewald et al., 2008). These 35-kDa proteins
      represent a novel group of molybdenum proteins in eukaryotes as they form a
      molybdenum cofactor-dependent enzyme system consisting of three separate proteins
      (Havemeyer et al., 2006). Each mARC protein reduces N-hydroxylated compounds
      after reconstitution with the electron transport proteins cytochrome b(5) and
      b(5) reductase. In continuation of our drug metabolism investigations (Havemeyer
      et al., 2006; Gruenewald et al., 2008), we present data from reconstituted enzyme
      systems with recombinant human and native porcine enzymes showing the reduction
      of N-hydroxy-sulfonamides (sulfohydroxamic acids) to sulfonamides: the N-hydroxy
      sulfonamide N-hydroxy-valdecoxib (N-hydroxy-4-[5-methyl-3-phenyl-4-isoxazolyl]
      benzenesulfonamide) represents a novel cyclooxygenase (COX)-2 inhibitor and is
      therefore a drug candidate in the treatment of diseases associated with rheumatic
      inflammation, pain, and fever. It was synthesized as an analog of the known COX-2
      inhibitor valdecoxib (4-[5-methyl-3-phenyl-4-isoxazolyl]-benzenesulfonamide)
      (Talley et al., 2000). N-Hydroxy-valdecoxib had low in vitro COX-2 activity but
      showed significant analgesic activity in vivo and a prolonged therapeutic effect
      compared with valdecoxib (Erdelyi et al., 2008). In this report, we demonstrate
      that N-hydroxy-valdecoxib is enzymatically reduced to its pharmacologically
      active metabolite valdecoxib. Thus, N-hydroxy-valdecoxib acts as prodrug that is
      activated by the molybdenum-containing enzyme mARC.

PMID- 20699409
TI  - A 96-well plate assay for CYP4503A induction using cryopreserved human
      hepatocytes.
AB  - A reliable and practical CYP3A induction assay with cryopreserved human
      hepatocytes in a 96-well format was developed. Various 96-well plates with
      different basement membrane were evaluated using prototypical inducers,
      rifampicin, phenytoin, and carbamazepine. Thin-layer (TL) Matrigel was found to
      yield the highest basal and induced levels of CYP3A activity as determined by
      testosterone 6beta-hydroxylation. Concentration-dependent CYP3A induction of
      rifampicin was reproducible with the EC(50) values of 0.36 +/- 0.28 MUM from four
      batches of human hepatocytes using the 96-well plate with TL Matrigel. The rank
      order of induction potency for nine inducers or noninducers at a concentration of
      10 MUM were well comparable among the multiple donors, by expressing the results
      as percentage of change compared with the positive control, 10 MUM rifampicin.
      Cotreatment of avasimibe or efavirenz with 10 MUM rifampicin was found to reduce
      CYP3A activities induced by rifampicin at a lower rate than treatment with
      rifampicin alone, whereas treatment with phenobarbital and carbamazepine had no
      effect. From a comparison of induced CYP3A activities and gene expression levels,
      there were compounds that would cause induction of CYP3A4 mRNA but not activity,
      presumably due to their inhibitory effect on CYP3A activity. The cotreatment
      assay of test compound with rifampicin allows us to exclude the false-negative
      results caused by the cytotoxicity and/or the mechanism-based inactivation, when
      the drug candidate's ability for CYP3A induction is evaluating the enzyme
      activity. This 96-well plate assay, which is robust, reproducible, and
      convenient, has demonstrated the paramount applicability to the early drug
      discovery stage.

PMID- 20699410
TI  - ATP-binding cassette B1 transports seliciclib (R-roscovitine), a cyclin-dependent
      kinase inhibitor.
AB  - Seliciclib, a cyclin-dependent kinase inhibitor, is a promising candidate to
      treat a variety of cancers. Pharmacokinetic studies have shown high oral
      bioavailability but limited brain exposure to the drug. This study shows that
      seliciclib is a high-affinity substrate of ATP-binding cassette B1 (ABCB1)
      because it activates the ATPase activity of the transporter with an EC(50) of 4.2
      MUM and shows vectorial transport in MDCKII-MDR1 cells, yielding an efflux ratio
      of 8. This interaction may be behind the drug's limited penetration of the blood
      brain barrier. ABCB1 overexpression, on the other hand, does not confer
      resistance to the drug in the models tested. These findings should be considered
      when treatment strategies using seliciclib are designed.

PMID- 20699411
TI  - Metabolism, excretion, and pharmacokinetics of [14C]INCB018424, a selective Janus
      tyrosine kinase 1/2 inhibitor, in humans.
AB  - The metabolism, excretion, and pharmacokinetics of 3-(4-(7H-pyrrolo[2,3
      d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile (INCB018424), a
      potent, selective inhibitor of Janus tyrosine kinase1/2 and the first
      investigational drug of its class in phase III studies for the treatment of
      myelofibrosis, were investigated in healthy human subjects given a single oral 25
      mg dose of [(14)C]INCB018424 as an oral solution. INCB018424 and total
      radioactivity were absorbed rapidly (mean time to reach the maximal drug
      concentration <1 h), declining in a monophasic or biphasic fashion (mean t(1/2)
      of 2.32 and 5.81 h, respectively). Recovery of administered radioactivity was
      fairly rapid (>70% within 24 h postdose) with 74 and 22% recovered in urine and
      feces, respectively. Parent compound was the predominant entity in the
      circulation, representing 58 to 74% of the total radioactivity up to 6 h
      postdose, indicating that the overall circulating metabolite burden was low (<50%
      of parent). Two metabolite peaks in plasma (M18 and a peak containing M16/M27,
      both hydroxylations on the cyclopentyl moiety) were identified as major (30 and
      14% of parent based on area under the curve from 0 to 24 h). The exposures of
      other circulating INCB018424-related peaks were <10% of parent, consisting of
      mono- and dihydroxylated metabolites. The profiles in urine and feces consisted
      of hydroxyl and oxo metabolites and subsequent glucuronide conjugates with parent
      drug accounting for <1% of the excreted dose, strongly suggesting that after an
      oral dose, INCB018424 was >95% absorbed. In healthy subjects administered daily
      oral doses of unlabeled INCB018424, there were minimal differences in parent and
      metabolite concentrations between day 1 and day 10, indicating a lack of
      accumulation of parent or metabolites between single and multiple dosing.

PMID- 20699412
TI  - CYP2C8 exists as a dimer in natural membranes.
AB  - CYP2C8 with a modified N-terminal sequence (2C8H) crystallizes as a dimer, but it
      is not known whether native CYP2C8 exists as a dimer in natural membranes. We
      have examined the organization of 2C8H and CYP2C8 expressed in bacterial
      membranes and mammalian endoplasmic reticulum membranes, respectively, by
      cysteine scanning and cross-linking or oxidation of sulfhydryl groups. In both
      forms of CYP2C8, cross-linked dimers were observed that were eliminated by
      mutation of Cys-24 in the linker region. Introduction of individual cysteines in
      the N-terminal 21-amino acid membrane-spanning signal anchor resulted in a
      pattern of cross-linking consistent with an alpha-helical structure for the
      signal anchor. In the linker region, cross-linking was observed for cysteine
      substituted at residues 22, 23, or 24, just before three Arg residues, indicating
      close apposition of the two linker sequences despite the neighboring positive
      charges. Introduction into the F-G loop region of cysteine pairs optimally
      located for cross-linking based on the crystal structure resulted in cross-linked
      dimers in the Cys-24 mutant. Deletion of the signal anchor sequence eliminated
      cross-linking mediated by Cys-24 or by cysteines introduced in the F-G loop
      regions, indicating that the signal anchor interaction is required for stable
      dimer formation. These results indicate that the signal anchor sequence and the F
      G loop region form interfaces for CYP2C8 intermolecular interactions in natural
      membranes.

PMID- 20699413
TI  - Synthetic progestins differentially promote or prevent 7,12
      dimethylbenz(a)anthracene-induced mammary tumors in sprague-dawley rats.
AB  - Recent clinical trials show that combined oral dosing with estrogen and progestin
      increases the incidence of breast cancer in postmenopausal women. Similarly, in a
      rat model system of mammary carcinogenesis, the synthetic progestin
      medroxyprogesterone acetate (MPA) decreases latency and increases incidence of
      7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary tumors. The goal of this
      study was to compare the effects of four clinically relevant progestins, MPA,
      norgestrel (N-EL), norethindrone (N-ONE), and megestrol acetate (MGA), on DMBA
      induced mammary carcinogenesis in the rat. The experimental protocol involved
      implantation of 60-day release progestin pellets four weeks after rats were
      treated with DMBA. In contrast to the effect of MPA, N-ONE, and N-EL, but not
      MGA, blocked DMBA-dependent carcinogenesis and a dose-dependent effect on tumor
      growth was shown for N-EL; MGA did not alter tumor growth. Histopathologic
      studies showed extensive hyperplastic lesions in mammary tissue of progestin
      treated animals. Furthermore, following treatment with N-EL or N-ONE,
      immunohistochemical staining for vascular endothelial growth factor in
      hyperplastic mammary tissue was lower than in animals treated with DMBA plus MPA
      or DMBA alone. Expression of vascular endothelial growth factor receptor-1,
      estrogen receptor alpha, and progesterone receptor was also lower in hyperplastic
      mammary tissue in N-EL-, N-ONE-, and MGA-treated animals. Interestingly, N-EL
      stimulated progression of existing mammary tumors in DMBA/MPA-treated rats,
      suggesting stage-specific effects of N-EL in this model. Because N-EL and N-ONE
      prevent tumor growth in the early stages of DMBA-induced mammary carcinogenesis
      in rats, these progestins may have potential as chemopreventive agents in women
      with no history of breast disease or family history of breast cancer.

PMID- 20699415
TI  - DNA methylation markers for prostate cancer with a stem cell twist.
AB  - This perspective on Ibragimova et al. (beginning on page 1084 in this issue of
      the journal) highlights the potential role of DNA methylation-based markers in
      the early detection of prostate cancer (PCa), with a focus on the global
      reactivation of expression of genes epigenetically silenced in PCa cell lines.
      Novel findings of these investigators identified four genes methylated
      specifically in PCa, including the stem cell marker TACSTD2, which seems to
      discriminate PCa (methylated TACSTD2) from prostatic intraepithelial neoplasia
      (unmethylated). These genes add significantly to the list of epigenetic markers
      showing promise for clinical early detection of PCa in the near future.

PMID- 20699414
TI  - Global reactivation of epigenetically silenced genes in prostate cancer.
AB  - Transcriptional silencing associated with aberrant promoter hypermethylation is a
      common mechanism of inactivation of tumor suppressor genes in cancer cells. To
      globally profile the genes silenced by hypermethylation in prostate cancer, we
      screened a whole genome expression microarray for genes reactivated in the LNCaP,
      DU-145, PC-3, and MDA2b prostate tumor cell lines after treatment with the
      demethylating drug 5-aza-2-deoxycytidine and the histone deacetylation-inhibiting
      drug trichostatin A. A total of 2,997 genes showed at least 2-fold upregulation
      of expression after drug treatment in at least one prostate tumor cell line. For
      validation, we examined the first 45 genes, ranked by upregulation of expression,
      which had a typical CpG island and were known to be expressed in the normal cell
      counterpart. Two important findings were, first, that several genes known to be
      frequently hypermethylated in prostate cancer were apparent, and, second, that
      validation studies revealed eight novel genes hypermethylated in the prostate
      tumor cell lines, four of which were unmethylated in normal prostate cells and
      hypermethylated in primary prostate tumors (SLC15A3, 66%; KRT7, 54%; TACSTD2,
      17%; GADD45b, 3%). Thus, we established the utility of our screen for genes
      hypermethylated in prostate cancer cells. One of the novel genes was
      TACSTD2/TROP2, a marker of human prostate basal cells with stem cell
      characteristics. TACSTD2 was unmethylated in prostatic intraepithelial neoplasia
      and may have utility in emerging methylation-based prostate cancer tests. Further
      study of the hypermethylome will provide insight into the biology of the disease
      and facilitate translational studies in prostate cancer.

PMID- 20699416
TI  - DsbA-L alleviates endoplasmic reticulum stress-induced adiponectin
      downregulation.
AB  - OBJECTIVE: Obesity impairs adiponectin expression, assembly, and secretion, yet
      the underlying mechanisms remain elusive. The aims of this study were 1) to
      determine the molecular mechanisms by which obesity impairs adiponectin
      multimerization and stability, and 2) to determine the potential role of
      disulfide-bond-A oxidoreductase-like protein (DsbA-L), a recently identified
      adiponectin interactive protein that promotes adiponectin multimerization and
      stability in obesity-induced endoplasmic reticulum (ER) stress and adiponectin
      downregulation. RESEARCH DESIGN AND METHODS: Tauroursodeoxycholic acid (TUDCA), a
      chemical chaperone that alleviates ER stress, was used to study the mechanism
      underlying obesity-induced adiponectin downregulation in db/db mice, high-fat
      diet-induced obese mice, and in ER-stressed 3T3-L1 adipocytes. The cellular
      levels of DsbA-L were altered by RNAi-mediated suppression or adenovirus-mediated
      overexpression. The protective role of DsbA-L in obesity- and ER stress-induced
      adiponectin downregulation was characterized. RESULTS: Treating db/db mice and
      diet-induced obese mice with TUDCA increased the cellular and serum levels of
      adiponectin. In addition, inducing ER stress is sufficient to downregulate
      adiponectin levels in 3T3-L1 adipocytes, which could be protected by treating
      cells with the autophagy inhibitor 3-methyladenine or by overexpression of DsbA
      L. CONCLUSIONS: ER stress plays a key role in obesity-induced adiponectin
      downregulation. In addition, DsbA-L facilitates adiponectin folding and assembly
      and provides a protective effect against ER stress-mediated adiponectin
      downregulation in obesity.

PMID- 20699417
TI  - Glucagon supports postabsorptive plasma glucose concentrations in humans with
      biologically optimal insulin levels.
AB  - OBJECTIVE: Based on the premise that postabsorptive patients with type 1 diabetes
      receiving intravenous insulin in a dose that maintains stable euglycemia are
      receiving biologically optimal insulin replacement, we tested the hypothesis that
      glucagon supports postabsorptive plasma glucose concentrations in humans.
      RESEARCH DESIGN AND METHODS: Fourteen patients with type 1 diabetes were studied
      after an overnight fast on up to five occasions. Insulin was infused
      intravenously to hold plasma glucose concentrations at ~100 mg/dl (5.6 mmol/l)
      overnight and fixed from -60 to 240 min the following morning. From 0 through 180
      min the patients also received 1) saline, 2) octreotide 30 ng . kg(-1) . min(-1)
      with growth hormone replacement or octreotide with growth hormone, plus 3)
      glucagon in doses of 0.5 ng . kg(-1) . min(-1), 4) 1.0 ng . kg(-1) . min(-1), and
      5) 2.0 ng . kg(-1) . min(-1). RESULTS: Compared with a mean +/- SE of 98 +/- 5
      mg/dl (5.4 +/- 0.3 mmol/l) at 180 min during saline, mean plasma glucose
      concentrations declined to 58 +/- 1 mg/dl (3.2 +/- 0.1 mmol/l) (P < 0.001) at 180
      min during octreotide plus saline and were 104 +/- 16 mg/dl (5.8 +/- 0.9 mmol/l)
      (NS), 143 +/- 13 mg/dl (7.9 +/- 0.7 mmol/l) (P = 0.004), and 160 +/- 15 mg/dl
      (8.9 +/- 0.8 mmol/l) (P < 0.001) at 180 min during octreotide plus glucagon in
      doses of 0.5, 1.0, and 2.0 ng . kg(-1) . min(-1), respectively. CONCLUSIONS: In
      the setting of biologically optimal insulin replacement, suppression of glucagon
      secretion with octreotide caused a progressive fall in plasma glucose
      concentrations that was prevented by glucagon replacement. These data document
      that glucagon supports postabsorptive glucose concentrations in humans.

PMID- 20699418
TI  - Diabetic nephropathy is accelerated by farnesoid X receptor deficiency and
      inhibited by farnesoid X receptor activation in a type 1 diabetes model.
AB  - OBJECTIVE: The pathogenesis of diabetic nephropathy is complex and involves
      activation of multiple pathways leading to kidney damage. An important role for
      altered lipid metabolism via sterol regulatory element binding proteins (SREBPs)
      has been recently recognized in diabetic kidney disease. Our previous studies
      have shown that the farnesoid X receptor (FXR), a bile acid-activated nuclear
      hormone receptor, modulates renal SREBP-1 expression. The purpose of the present
      study was then to determine if FXR deficiency accelerates type 1 diabetic
      nephropathy in part by further stimulation of SREBPs and related pathways, and
      conversely, if a selective FXR agonist can prevent the development of type 1
      diabetic nephropathy. RESEARCH DESIGN AND METHODS: Insulin deficiency and
      hyperglycemia were induced with streptozotocin (STZ) in C57BL/6 FXR KO mice.
      Progress of renal injury was compared with nephropathy-resistant wild-type
      C57BL/6 mice given STZ. DBA/2J mice with STZ-induced hyperglycemia were treated
      with the selective FXR agonist INT-747 for 12 weeks. To accelerate disease
      progression, all mice were placed on the Western diet after hyperglycemia
      development. RESULTS: The present study demonstrates accelerated renal injury in
      diabetic FXR KO mice. In contrast, treatment with the FXR agonist INT-747
      improves renal injury by decreasing proteinuria, glomerulosclerosis, and
      tubulointerstitial fibrosis, and modulating renal lipid metabolism, macrophage
      infiltration, and renal expression of SREBPs, profibrotic growth factors, and
      oxidative stress enzymes in the diabetic DBA/2J strain. CONCLUSIONS: Our findings
      indicate a critical role for FXR in the development of diabetic nephropathy and
      show that FXR activation prevents nephropathy in type 1 diabetes.

PMID- 20699419
TI  - Enhanced levels of microRNA-125b in vascular smooth muscle cells of diabetic
      db/db mice lead to increased inflammatory gene expression by targeting the
      histone methyltransferase Suv39h1.
AB  - OBJECTIVE: Diabetes remains a major risk factor for vascular complications that
      seem to persist even after achieving glycemic control, possibly due to "metabolic
      memory." Using cultured vascular smooth muscle cells (MVSMC) from type 2 diabetic
      db/db mice, we recently showed that decreased promoter occupancy of the chromatin
      histone H3 lysine-9 methyltransferase Suv39h1 and the associated repressive
      epigenetic mark histone H3 lysine-9 trimethylation (H3K9me3) play key roles in
      sustained inflammatory gene expression. Here we examined the role of microRNAs
      (miRs) in Suv39h1 regulation and function in MVSMC from diabetic mice. RESEARCH
      DESIGN AND METHODS: We used luciferase assays with Suv39h1 3'untranslated region
      (UTR) reporter constructs and Western blotting of endogenous protein to verify
      that miR-125b targets Suv39h1. We examined the effects of Suv39h1 targeting on
      inflammatory gene expression by quantitative real time polymerase chain reaction
      (RT-qPCR), and H3K9me3 levels at their promoters by chromatin immunoprecipitation
      assays. RESULTS: We observed significant upregulation of miR-125b with parallel
      downregulation of Suv39h1 protein (predicted miR-125b target) in MVSMC cultured
      from diabetic db/db mice relative to control db/+. miR-125b mimics inhibited both
      Suv39h1 3'UTR luciferase reporter activity and endogenous Suv39h1 protein levels.
      Conversely, miR-125b inhibitors showed opposite effects. Furthermore, miR-125b
      mimics increased expression of inflammatory genes, monocyte chemoattractant
      protein-1, and interleukin-6, and reduced H3K9me3 at their promoters in
      nondiabetic cells. Interestingly, miR-125b mimics increased monocyte binding to
      db/+ MVSMC toward that in db/db MVSMC, further imitating the proinflammatory
      diabetic phenotype. In addition, we found that the increase in miR-125b in db/db
      VSMC is caused by increased transcription of miR-125b-2. CONCLUSIONS: These
      results demonstrate a novel upstream role for miR-125b in the epigenetic
      regulation of inflammatory genes in MVSMC of db/db mice through downregulation of
      Suv39h1.

PMID- 20699420
TI  - Residual insulin production and pancreatic beta-cell turnover after 50 years of
      diabetes: Joslin Medalist Study.
AB  - OBJECTIVE: To evaluate the extent of pancreatic beta-cell function in a large
      number of insulin-dependent diabetic patients with a disease duration of 50 years
      or longer (Medalists). RESEARCH DESIGN AND METHODS: Characterization of clinical
      and biochemical parameters and beta-cell function of 411 Medalists with
      correlation with postmortem morphologic findings of 9 Medalists. RESULTS: The
      Medalist cohort, with a mean +/- SD disease duration and age of 56.2 +/- 5.8 and
      67.2 +/- 7.5 years, respectively, has a clinical phenotype similar to type 1
      diabetes (type 1 diabetes): mean +/- SD onset at 11.0 +/- 6.4 years, BMI at 26.0
      +/- 5.1 kg/m(2), insulin dose of 0.46 +/- 0.2 u/kg, ~94% positive for DR3 and/or
      DR4, and 29.5% positive for either IA2 or glutamic acid decarboxylase (GAD)
      autoantibodies. Random serum C-peptide levels showed that more than 67.4% of the
      participants had levels in the minimal (0.03-0.2 nmol/l) or sustained range (>=
      0.2 nmol/l). Parameters associated with higher random C-peptide were lower
      hemoglobin A1C, older age of onset, higher frequency of HLA DR3 genotype, and
      responsiveness to a mixed-meal tolerance test (MMTT). Over half of the Medalists
      with fasting C-peptide > 0.17 nmol/l responded in MMTT by a twofold or greater
      rise over the course of the test compared to fasting. Postmortem examination of
      pancreases from nine Medalists showed that all had insulin+ beta-cells with some
      positive for TUNEL staining, indicating apoptosis. CONCLUSIONS: Demonstration of
      persistence and function of insulin-producing pancreatic cells suggests the
      possibility of a steady state of turnover in which stimuli to enhance endogenous
      beta cells could be a viable therapeutic approach in a significant number of
      patients with type 1 diabetes, even for those with chronic duration.

PMID- 20699421
TI  - Proteomic analysis of electronegative low-density lipoprotein.
AB  - Low density lipoprotein is a heterogeneous group of lipoproteins that differs in
      lipid and protein composition. One copy of apolipoprotein (apo)B accounts for
      over 95% of the LDL protein, but the presence of minor proteins could disturb its
      biological behavior. Our aim was to study the content of minor proteins in LDL
      subfractions separated by anion exchange chromatography. Electropositive LDL
      [LDL(+)] is the native form, whereas electronegative LDL [LDL-] is a minor
      atherogenic fraction present in blood. LC-ESI MS/MS analysis of both LDL
      fractions identified up to 28 different proteins. Of these, 13 proteins,
      including apoB, were detected in all the analyzed samples. LDL- showed a higher
      content of most minor proteins. Statistical analysis of proteomic data indicated
      that the content of apoE, apoA-I, apoC-III, apoA-II, apoD, apoF, and apoJ was
      higher in LDL- than in LDL(+). Immunoturbidimetry, ELISA, or Western blot
      analysis confirmed these differences. ApoJ and apoF presented the highest
      difference between LDL(+) and LDL- (>15-fold). In summary, the increased content
      of several apolipoproteins, and specifically of apoF and apoJ, could be related
      to the physicochemical characteristics of LDL-, such as apoB misfolding,
      aggregation, and abnormal lipid composition.

PMID- 20699422
TI  - In memoriam: Stewart Charles Whitman (1964-2010).

PMID- 20699423
TI  - Niemann-Pick C1-Like 1 deletion in mice prevents high-fat diet-induced fatty
      liver by reducing lipogenesis.
AB  - Niemann-Pick C1-Like 1 (NPC1L1) mediates intestinal absorption of dietary and
      biliary cholesterol. Ezetimibe, by inhibiting NPC1L1 function, is widely used to
      treat hypercholesterolemia in humans. Interestingly, ezetimibe treatment appears
      to attenuate hepatic steatosis in rodents and humans without a defined mechanism.
      Over-consumption of a high-fat diet (HFD) represents a major cause of metabolic
      disorders including fatty liver. To determine whether and how NPC1L1 deficiency
      prevents HFD-induced hepatic steatosis, in this study, we fed NPC1L1 knockout (L1
      KO) mice and their wild-type (WT) controls an HFD, and found that 24 weeks of HFD
      feeding causes no fatty liver in L1-KO mice. Hepatic fatty acid synthesis and
      levels of mRNAs for lipogenic genes are substantially reduced but hepatic
      lipoprotein-triglyceride production, fatty acid oxidation, and triglyceride
      hydrolysis remain unaltered in L1-KO versus WT mice. Strikingly, L1-KO mice are
      completely protected against HFD-induced hyperinsulinemia under both fed and
      fasted states and during glucose challenge. Despite similar glucose tolerance, L1
      KO relative WT mice are more insulin sensitive and in the overnight-fasted state
      display significantly lower plasma glucose concentrations. In conclusion, NPC1L1
      deficiency in mice prevents HFD-induced fatty liver by reducing hepatic
      lipogenesis, at least in part, through attenuating HFD-induced insulin
      resistance, a state known to drive hepatic lipogenesis through elevated
      circulating insulin levels.

PMID- 20699424
TI  - Effects of PCSK9 genetic variants on plasma LDL cholesterol levels and risk of
      premature myocardial infarction in the Italian population.
AB  - The R46L variant in the proprotein-convertase subtilisin-kexin type 9 (PCSK9)
      gene was associated with reduced levels of LDL and total cholesterol and with a
      lower risk of coronary artery disease. We investigated the association of R46L
      with myocardial infarction (MI) in 1,880 Italian patients with premature MI and
      1,880 controls. A trend toward a protective effect of the L46 allele was observed
      [odds ratio (OR) = 0.75, 95% confidence interval (CI) = 0.49-1.13; P = 0.17],
      although the association with MI was not significant. This is probably due to the
      combined effect of the low frequency of R46L among Italians and of the young age
      of the analyzed cohort for whom the impact of coronary atherosclerosis is less
      important. This hypothesis was indirectly confirmed by the significant
      association found after including 1,056 additional older controls (OR = 0.67, 95%
      CI = 0.46-0.97; P = 0.036). LDL cholesterol was significantly lower in L46
      carriers (116.2 +/- 34.7 mg/dl) than in noncarriers (137.4 +/- 47.3 mg/dl; P =
      0.00022); a similar reduction was observed for total cholesterol (191.7 +/- 37.7
      vs. 211.7 +/- 49 mg/dl; P = 0.00019). Analysis of 23 additional polymorphisms in
      the PCSK9 region identified another single nucleotide polymorphism (SNP)
      (rs11206510) associated with cholesterol levels. We confirmed that the L46 allele
      not only decreases LDL cholesterol but also protects against MI. Moreover, we
      replicated the association of total and LDL cholesterol with the SNP rs11206510.

PMID- 20699425
TI  - Cell therapy in tendon disorders: what is the current evidence?
AB  - BACKGROUND: Various types of tissue-derived cells are being experimented with for
      the treatment of tendinopathy, tendon repair, and use in tissue engineering.
      PURPOSE: The aim of this systematic review is to explore the current evidence
      with a view to evaluate the potential of this therapeutic intervention. STUDY
      DESIGN: Systematic review. METHODS: A review of the literature was conducted
      using PubMed. Search criteria included keywords "tendinopathy," "tendinitis,"
      "tendinosis," "epicondylitis," "stem cell," and "cell therapy." Articles not
      written in English language were excluded. RESULTS: A total number of 379
      articles were identified and a critical appraisal of the relevant articles was
      undertaken, which encompassed human and animal research. The review included
      articles related to various tissue-derived cells such as tendon progenitors,
      adipose tissue, synovium, muscle, bone marrow, and skin. The utility of cell
      therapy in tissue engineering and rotator cuff repair was also assessed.
      CONCLUSION: With the limitation of the available evidence, the literature
      suggests that cell therapy is applicable and may be effective for the treatment
      of tendinopathy. However, further research into the precise biological
      mechanisms, long-term implications, and cost-effectiveness is needed.

PMID- 20699426
TI  - Intrinsic risk factors for groin injuries among male soccer players: a
      prospective cohort study.
AB  - BACKGROUND: This study was conducted to determine if risk factors for groin
      injuries among male soccer players could be identified. HYPOTHESIS: Previous
      groin injuries, reduced function scores, age, findings on clinical examination,
      and low isometric groin strength are associated with increased risk of new groin
      injuries. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A total of
      508 players representing 31 amateur teams were tested during the 2004 preseason
      for potential risk factors for groin injury through a questionnaire on previous
      injury and function score (Groin Outcome Score [GrOS]) and a clinical examination
      of the groin. Generalized estimating equations were used in univariate analyses
      to identify candidate risk factors, and factors with a P value <.10 were then
      examined in a multivariate model. RESULTS: During the soccer season, 61 groin
      injuries affecting 55 legs (51 players) were registered. The total incidence of
      groin injuries was 0.6 injuries per 1000 playing hours (95% confidence interval
      [CI], 0.4-0.7), 0.3 injuries per 1000 training hours (95% CI, 0.2-0.4), and 1.8
      injuries per 1000 match hours (95% CI, 1.2-2.5). In a multivariate analysis,
      previous acute groin injury (adjusted odds ratio [OR], 2.60; 95% CI, 1.10-6.11)
      and weak adductor muscles as determined clinically (adjusted OR, 4.28; 95% CI,
      1.31-14.0) were significantly associated with increased risk of groin injuries. A
      multivariate analysis based only on acute time-loss injuries revealed the 40-m
      sprint test result (adjusted OR, 2.03 for 1 standard deviation change [injured
      group faster]; 95% CI, 1.06-3.88; P = .03) and functional testing of the rectal
      abdominal muscles (adjusted OR, 15.5 [painful in 19% of the players in the
      injured group compared to 16% in the uninjured group]; 95% CI, 1.11-217; P = .04)
      as significant risk factors. CONCLUSION: A history of acute groin injury and weak
      adductor muscles are significant risk factors for new groin injuries.

PMID- 20699427
TI  - The effect of distal clavicle excision on in situ graft forces in
      coracoclavicular ligament reconstruction.
AB  - BACKGROUND: Recently, some have suggested that the acromioclavicular articulation
      confers stability to the construct after coracoclavicular ligament reconstruction
      for acromioclavicular joint separation. Therefore, it has been suggested that
      distal clavicle excision should not be performed in this context to protect the
      graft during healing. HYPOTHESIS: Sectioning the acromioclavicular ligaments
      would significantly increase in situ forces of a coracoclavicular ligament graft,
      whereas performing a distal clavicle resection would not further increase in situ
      graft forces. DESIGN: Controlled laboratory study. METHODS: A simulated
      coracoclavicular reconstruction was performed on 5 cadaveric shoulders. Static
      loads of 80 N and 210 N were applied directly to the clavicle in 5 directions:
      anterior, anterosuperior, superior, posterosuperior, and posterior. The in situ
      graft force was measured using a force transducer under 3 testing conditions: (1)
      intact acromioclavicular ligaments, (2) sectioned acromioclavicular ligaments,
      and (3) distal clavicle excision. RESULTS: For both magnitudes of load, in all
      directions, in situ graft force with intact acromioclavicular ligaments was
      significantly less than that with sectioned acromioclavicular ligaments (P <
      .001). Distal clavicle excision did not further increase the in situ graft forces
      with load applied to the clavicle in an anterior, anterosuperior, or superior
      direction. However, in situ graft forces were increased with distal clavicle
      excision when the clavicle was loaded with 210 N in the posterosuperior direction
      (60.4 +/- 6.3 N vs 52.5 +/- 7.1 N; P = .048) and tended to be increased with
      posterior loading of the clavicle (71.8 +/- 6.2 N vs 53.1 +/- 8.8 N; P = .125).
      CONCLUSION: Intact acromioclavicular ligaments protect the coracoclavicular
      reconstruction by decreasing the in situ graft force. The slight increase in the
      in situ graft force only in the posterosuperior and posterior direction after
      distal clavicle excision suggests only a marginal protective role of the
      acromioclavicular articulation. Further, the peak graft forces observed represent
      only a small fraction of the ultimate failure strength of the graft. CLINICAL
      RELEVANCE: Distal clavicle excision can perhaps be safely performed in the
      context of coracoclavicular ligament reconstruction without subjecting the graft
      to detrimental in situ force. Although the acromioclavicular articulation serves
      only a marginal role in protecting the coracoclavicular ligament graft,
      reconstruction of the acromioclavicular ligaments may serve an important role in
      decreasing in situ graft force during healing.

PMID- 20699428
TI  - Results of laboratory evaluation of acute knee effusion after anterior cruciate
      ligament reconstruction: what is found in patients with a noninfected, painful
      postoperative knee?
AB  - BACKGROUND: Infection after anterior cruciate ligament reconstruction is a rare
      and potentially devastating complication. No normative data have been reported
      for knee aspiration after anterior cruciate ligament reconstruction in the early
      postoperative period. HYPOTHESIS: Determining normative laboratory data from a
      retrospective review of noninfected early postoperative anterior cruciate
      ligament reconstruction knee effusions will allow for the calculation of an
      aspirate white blood cell (WBC) threshold value indicative of infection. STUDY
      DESIGN: Case series (diagnosis); Level of evidence, 4. METHODS: A 2-year
      retrospective chart review of 151 anterior cruciate ligament reconstruction
      patients was performed. Thirty-one noninfected patients meeting the inclusion and
      exclusion criteria and 1 infected patient had laboratory data collected,
      including peripheral blood and knee effusion aspirate analyses. Laboratory data
      from pertinent published studies of infected knees after anterior cruciate
      ligament reconstruction were combined with the data of our 1 infected patient,
      establishing a historical control group. Data were analyzed and results were then
      compared. Infected aspirate WBC threshold value statistics were then calculated.
      RESULTS: Analysis of noninfected knee effusion aspirates revealed a mean WBC
      count of 9600/uL (standard deviation [SD], 15 200), and a mean of 66%
      polymorphonuclear (PMN) cells (SD, 34). Aspirate WBC 98% confidence interval (CI)
      was 2800/uL to 16 200/uL, and the 98% CI for PMN cells was 58% to 84%. Aspirate
      WBC count >16 200/uL is 86% sensitive, 92% specific, and has a positive
      likelihood ratio of 10.4 as an indicator of infection. CONCLUSION: Benign
      effusion after anterior cruciate ligament reconstruction is common and is
      associated with elevated inflammatory markers. When concerned, knee aspiration
      after anterior cruciate ligament surgery gives the highest yield to differentiate
      between a painful effusion and a septic knee in the early postoperative period
      while awaiting definitive culture results. The authors report confidence
      intervals defining the range of cell count variables for noninfected patients
      requiring aspiration, specifically WBC and PMN, and suggest a WBC threshold value
      of >16 200/uL be used as an indicator of infection. On the basis of comparison
      with historical control data, the authors believe these data are significant and
      will be reliable for clinical use.

PMID- 20699429
TI  - Potential savings of a program to prevent ankle sprain recurrence: economic
      evaluation of a randomized controlled trial.
AB  - BACKGROUND: The most common ankle injury is the lateral ankle sprain. Dutch
      annual sports-related ankle sprain costs can roughly be estimated at
      ?187,200,000. Research has shown that proprioceptive training accounts for an
      approximated overall 50% reduction in ankle sprain recurrence rate. HYPOTHESIS:
      An unsupervised proprioceptive training program to reduce the recurrence of
      lateral ankle sprains will reduce overall health care costs. DESIGN: Cohort study
      (economic analysis); Level of evidence, 2. METHODS: The study included 522 male
      and female athletes: 256 athletes (120 female and 136 male) in the intervention
      group, and 266 athletes (128 female and 138 male) in the control group. Both
      groups received treatment according to usual care. Athletes allocated to the
      intervention group received an 8-week proprioceptive training program in addition
      to usual care. Costs per athlete and costs per injured athlete were calculated.
      Costs related to ankle sprain recurrences were measured from a societal
      perspective using cost diaries. Bootstrapping was used to analyze the cost
      effectiveness data. Follow-up was 1 year. RESULTS: Mean total costs in the
      intervention group were ?81 (standard deviation, ?134) per athlete and ?114
      (?325) per injured athlete. Mean overall costs in the control group were ?149
      (?836) per athlete and ?447 (?1403) per injured athlete. Statistically
      significant differences in total costs were found per athlete (mean difference, 
      ?69; 95% confidence interval, -?200 to -?2) and per injured athlete (-?332; -?741
      to -?62) in favor of the intervention group. A cost-effectiveness plane showed
      the effect of the intervention was larger and the costs were lower in the
      intervention group than the control group. CONCLUSION: The use of a
      proprioceptive training program after usual care of an ankle sprain is cost
      effective for the prevention of ankle sprain recurrences in comparison with usual
      care alone. In the Netherlands, an estimated annual ?35.9 million in medical and
      lost productivity costs can be saved solely by advocating a proprioceptive
      training program as in the present study.

PMID- 20699430
TI  - Gracilis autograft for recurrent posttraumatic instability of the superior
      tibiofibular joint.
AB  - BACKGROUND: Several reconstruction procedures have been proposed to manage
      recurrent dislocation of the superior tibiofibular joint. HYPOTHESIS:
      Reconstruction of the superior tibiofibular joint using a gracilis tendon
      autograft is effective in recurrent dislocation of the superior tibiofibular
      joint. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Eight patients
      with recurrent dislocation of the superior tibiofibular joint without anatomical
      predisposing factors and who practiced sports were included in the study.
      Evaluation included the modified Cincinnati rating system and the Kujala score,
      anthropometry, plain radiography, and isokinetic dynamometry. RESULTS: The
      average follow-up was 44 +/- 13 months. The mean modified Cincinnati score
      increased from 54 preoperatively to 92 (P = .01). The mean Kujala scores
      increased from 48 preoperatively to 85 (P = .05). The muscle volume of the thigh
      of the operated limb remained less well developed than the muscle volume of the
      nonoperated limb (P = .05). Significant isokinetic strength differences were
      found between the operated and the contralateral limb (P = .02) even at the
      latest follow-up. CONCLUSION: Gracilis autograft for posttraumatic instability of
      the superior tibiofibular joint is a safe, reliable management option for
      recurrent dislocation of the superior tibiofibular joint in patients without any
      predisposing factors.

PMID- 20699431
TI  - The effect of Reiki on work-related stress of the registered nurse.
AB  - PURPOSE: The Reiki Master Teacher group at a large academic, urban medical center
      studied the effects of Reiki on work-related stress in Registered Nurse Reiki I
      class participants. Research suggests that work-related stress is an influential
      factor in nursing burn out and retention. Reiki, an ancient form of Oriental
      "energy work" or healing, has been found to decrease stress. METHODS: The
      Perceived Stress Scale tool was administered prior to the Reiki I class and after
      three weeks of practicing self-Reiki. FINDINGS: Seventeen participants returned
      follow-up data. Results indicated that practicing Reiki more often resulted in
      reduced perceived stress levels. CONCLUSIONS: Data from this small pilot study
      supports educating nurses about Reiki practice to decrease work-related stress.

PMID- 20699432
TI  - Type 1 diabetic drivers with and without a history of recurrent hypoglycemia
      related driving mishaps: physiological and performance differences during
      euglycemia and the induction of hypoglycemia.
AB  - OBJECTIVE: Collisions are more common among drivers with type 1 diabetes than
      among their nondiabetic spouses. This increased risk appears to be attributable
      to a subgroup of drivers with type 1 diabetes. The hypothesis tested is that this
      vulnerable subgroup is more at risk for hypoglycemia and its disruptive effects
      on driving. RESEARCH DESIGN AND METHODS: Thirty-eight drivers with type 1
      diabetes, 16 with (+history) and 22 without (-history) a recent history of
      recurrent hypoglycemia-related driving mishaps, drove a virtual reality driving
      simulator and watched a videotape of someone driving a simulator for 30-min
      periods. Driving and video testing occurred in a double-blind, randomized,
      crossover manner during euglycemia (5.5 mmol/l) and progressive hypoglycemia (3.9
      2.5 mmol/l). Examiners were blind to which subjects were +/-history, whereas
      subjects were blind to their blood glucose levels and targets. RESULTS: During
      euglycemia, +history participants reported more autonomic and neuroglycopenic
      symptoms (P<=0.01) and tended to require more dextrose infusion to maintain
      euglycemia with the same insulin infusion (P<0.09). During progressive
      hypoglycemia, these subjects demonstrated less epinephrine release (P=0.02) and
      greater driving impairments (P=0.03). CONCLUSIONS: Findings support the
      speculation that there is a subgroup of type 1 diabetic drivers more vulnerable
      to experiencing hypoglycemia-related driving mishaps. This increased
      vulnerability may be due to more symptom "noise" (more symptoms during
      euglycemia), making it harder to detect hypoglycemia while driving; possibly
      greater carbohydrate utilization, rendering them more vulnerable to experiencing
      hypoglycemia; less hormonal counterregulation, leading to more profound
      hypoglycemia; and more neuroglycopenia, rendering them more vulnerable to
      impaired driving.

PMID- 20699433
TI  - Insulin suppresses endotoxin-induced oxidative, nitrosative, and inflammatory
      stress in humans.
AB  - OBJECTIVE: To investigate whether insulin reduces the magnitude of oxidative,
      nitrosative, and inflammatory stress and tissue damage responses induced by
      endotoxin (lipopolysaccharide [LPS]). RESEARCH DESIGN AND METHODS: Nine normal
      subjects were injected intravenously with 2 ng/kg LPS prepared from Escherichia
      coli. Ten others were infused with insulin (2 units/h) for 6 h in addition to the
      LPS injection along with 100 ml/h of 5% dextrose to maintain normoglycemia.
      RESULTS: LPS injection induced a rapid increase in plasma concentrations of
      nitric oxide metabolites, nitrite and nitrate (NOM), and thiobarbituric acid
      reacting substances (TBARS), an increase in reactive oxygen species (ROS)
      generation by polymorphonuclear leukocytes (PMNLs), and marked increases in
      plasma free fatty acids, tumor necrosis factor-alpha (TNF-alpha), interleukin-6
      (IL-6), monocyte chemoattractant protein-1 (MCP-1), macrophage migration
      inhibition factor (MIF), C-reactive protein, resistin, visfatin,
      lipopolysaccharide binding protein (LBP), high mobility group-B1 (HMG-B1), and
      myoglobin concentrations. The coinfusion of insulin led to a total elimination of
      the increase in NOM, free fatty acids, and TBARS and a significant reduction in
      ROS generation by PMNLs and plasma MIF, visfatin, and myoglobin concentrations.
      Insulin did not affect TNF-alpha, MCP-1, IL-6, LBP, resistin, and HMG-B1
      increases induced by the LPS. CONCLUSIONS: Insulin reduces significantly several
      key mediators of oxidative, nitrosative, and inflammatory stress and tissue
      damage induced by LPS. These effects of insulin require further investigation for
      its potential use as anti-inflammatory therapy for endotoxemia.

PMID- 20699434
TI  - Age and sex differences in the clustering of metabolic syndrome factors:
      association with mortality risk.
AB  - OBJECTIVE: The metabolic syndrome is a general term given to a clustering of
      cardiometabolic risk factors that may consist of different phenotype
      combinations. The purpose of this study was to determine the prevalence of the
      different combinations of factors that make up the metabolic syndrome as defined
      by the National Cholesterol Education Program and to examine their association
      with all-cause mortality in younger and older men and women. RESEARCH DESIGN AND
      METHODS: A total of 2,784 men and 3,240 women from the Third National Health and
      Nutrition Examination Survey with public-access mortality data linkage (follow
      up=14.2+/-0.2 years) were studied. RESULTS: Metabolic syndrome was present in 26%
      of younger (aged<=65 years) and 55.0% of older (aged>65 years) participants. The
      most prevalent metabolic syndrome combination was the clustering of high
      triglycerides, low HDL cholesterol, and elevated blood pressure in younger men
      (4.8%) and triglycerides, HDL cholesterol, and elevated waist circumference in
      younger women (4.2%). The presence of all five metabolic syndrome factors was the
      most common metabolic syndrome combination in both older men (8.0%) and women
      (9.2%). Variation existed in how metabolic syndrome combinations were associated
      with mortality. In younger adults, having all five metabolic syndrome factors was
      most strongly associated with mortality risk, whereas in older men, none of
      metabolic syndrome combinations were associated with mortality. In older women,
      having elevated glucose or low HDL as one of the metabolic syndrome components
      was most strongly associated with mortality risk. CONCLUSIONS: Metabolic syndrome
      is a heterogeneous entity with age and sex variation in component clusters that
      may have important implications for interpreting the association between
      metabolic syndrome and mortality risk. Thus, metabolic syndrome used as a whole
      may mask important differences in assessing health and mortality risk.

PMID- 20699435
TI  - Myeloperoxidase expression as a potential determinant of parthenolide-induced
      apoptosis in leukemia bulk and leukemia stem cells.
AB  - Given that parthenolide (PTL) is an effective antileukemic agent, identifying
      molecular markers that predict response to PTL is important. We evaluated the
      role of myeloperoxidase (MPO) in determining the sensitivity of leukemia cells to
      PTL-induced apoptosis. In this study, the level of PTL-induced generation of
      reactive oxygen species (ROS) and apoptosis was significantly higher in the MPO
      high leukemia cell lines compared with the MPO-low leukemia cell lines.
      Pretreatment of MPO-high leukemia cells with a MPO-specific inhibitor, 4
      aminobenzoic acid hydrazide, or a MPO-specific small interfering RNA (siRNA)
      abrogated the PTL-induced ROS generation and apoptosis, indicating that MPO plays
      a crucial role in PTL-induced apoptosis in leukemia cells. PTL-induced apoptosis
      was accompanied by down-regulation of nuclear factor-kappaB, Bcl-xL, Mcl-1, X
      linked inhibitor of apoptosis protein, and survivin and selectively observed in
      primary acute myeloid leukemia (AML) cells expressing higher levels of MPO
      (>=50%) while sparing both AML cells with lower MPO and normal CD34-positive
      (CD34+) normal bone marrow cells. The extent of PTL-induced apoptosis of the
      CD34+CD38- cell fraction was significantly greater in the MPO-high AML cases,
      compared with the MPO-low AML (P < 0.01) and normal CD34+ marrow cells (P <
      0.01). Nonobese diabetic/severe combined immunodeficient human leukemia mouse
      model also revealed that PTL preferentially targets the MPO-high AML cells. Our
      data suggest that MPO plays a crucial role in determining the susceptibility of
      leukemia cells to PTL-induced apoptosis. PTL can be considered a promising
      leukemic stem cell-targeted therapy for AML expressing high levels of MPO.

PMID- 20699436
TI  - The vascular targeting agent combretastatin-A4 and a novel cis-Restricted {beta}
      Lactam Analogue, CA-432, induce apoptosis in human chronic myeloid leukemia cells
      and ex vivo patient samples including those displaying multidrug resistance.
AB  - Combretastatin-A4 (CA-4) is a natural derivative of the African willow tree
      Combretum caffrum. CA-4 is one of the most potent antimitotic components of
      natural origin, but it is, however, intrinsically unstable. A novel series of CA
      4 analogs incorporating a 3,4-diaryl-2-azetidinone (beta-lactam) ring were
      designed and synthesized with the objective to prevent cis -trans isomerization
      and improve the intrinsic stability without altering the biological activity of
      CA-4. Evaluation of selected beta-lactam CA-4 analogs demonstrated potent
      antitubulin, antiproliferative, and antimitotic effects in human leukemia cells.
      A lead beta-lactam analog, CA-432, displayed comparable antiproliferative
      activities with CA-4. CA-432 induced rapid apoptosis in HL-60 acute myeloid
      leukemia cells, which was accompanied by depolymerization of the microtubular
      network, poly(ADP-ribose) polymerase cleavage, caspase-3 activation, and Bcl-2
      cleavage. A prolonged G(2)M cell cycle arrest accompanied by a sustained
      phosphorylation of mitotic spindle checkpoint protein, BubR1, and the
      antiapoptotic proteins Bcl-2 and Bcl-x(L) preceded apoptotic events in K562
      chronic myeloid leukemia (CML) cells. Molecular docking studies in conjunction
      with comprehensive cell line data rule out CA-4 and beta-lactam derivatives as P
      glycoprotein substrates. Furthermore, both CA-4 and CA-432 induced significantly
      more apoptosis compared with imatinib mesylate in ex vivo samples from patients
      with CML, including those positive for the T315I mutation displaying resistance
      to imatinib mesylate and dasatinib. In summary, synthetic intrinsically stable
      analogs of CA-4 that display significant clinical potential as antileukemic
      agents have been designed and synthesized.

PMID- 20699437
TI  - Androgen deprivation induces rapid involution and recovery of human prostate
      vasculature.
AB  - The response of the prostate tissue microenvironment to androgen deprivation (AD)
      represents a critical component in the treatment of benign prostatic hyperplasia
      and prostate cancer (CaP). Primary xenografts of human benign and CaP tissue
      transplanted to immunocompromized SCID mice were used to characterize the
      response of the prostate vasculature during the initial 14 days of AD.
      Microvessel density and vascular lumen diameter in the prostate xenografts
      decreased rapidly after AD, reached a nadir on days 2-4, and recovered between
      days 4 and 14. The number of apoptotic endothelial cells peaked on day 2 after AD
      and decreased to precastration levels over days 4-7. Leakage of vascular contents
      in the interstitial space was apparent between days 1 and 3 after AD; however,
      the vascular permeability barrier reestablished between days 7 and 14. Expression
      of vascular endothelial growth factor (VEGF)-A, VEGF receptor-2, and basic
      fibroblast growth factor protein increased in endothelial cells between days 2
      and 4 after AD, which preceded vascular recovery and appeared to be a direct and
      specific response of the endothelial cells to AD. Lack of comparable upregulation
      of these genes in primary cultures of human prostate endothelial cells in
      response to AD suggests a role for paracrine signaling mediated through stromal
      or epithelial cells. VEGF-A expression by prostate endothelial cells appears to
      represent a key facilitator of the vascular rebound in human prostate tissue
      induced by removal of circulating testicular androgens.

PMID- 20699438
TI  - Identification of novel cluster groups in pediatric high-risk B-precursor acute
      lymphoblastic leukemia with gene expression profiling: correlation with genome
      wide DNA copy number alterations, clinical characteristics, and outcome.
AB  - To resolve the genetic heterogeneity within pediatric high-risk B-precursor acute
      lymphoblastic leukemia (ALL), a clinically defined poor-risk group with few known
      recurring cytogenetic abnormalities, we performed gene expression profiling in a
      cohort of 207 uniformly treated children with high-risk ALL. Expression profiles
      were correlated with genome-wide DNA copy number abnormalities and clinical and
      outcome features. Unsupervised clustering of gene expression profiling data
      revealed 8 unique cluster groups within these high-risk ALL patients, 2 of which
      were associated with known chromosomal translocations (t(1;19)(TCF3-PBX1) or
      MLL), and 6 of which lacked any previously known cytogenetic lesion. One unique
      cluster was characterized by high expression of distinct outlier genes AGAP1,
      CCNJ, CHST2/7, CLEC12A/B, and PTPRM; ERG DNA deletions; and 4-year relapse-free
      survival of 94.7% +/- 5.1%, compared with 63.5% +/- 3.7% for the cohort (P =
      .01). A second cluster, characterized by high expression of BMPR1B, CRLF2,
      GPR110, and MUC4; frequent deletion of EBF1, IKZF1, RAG1-2, and IL3RA-CSF2RA; JAK
      mutations and CRLF2 rearrangements (P < .0001); and Hispanic ethnicity (P < .001)
      had a very poor 4-year relapse-free survival (21.0% +/- 9.5%; P < .001). These
      studies reveal striking clinical and genetic heterogeneity in high-risk ALL and
      point to novel genes that may serve as new targets for diagnosis, risk
      classification, and therapy.

PMID- 20699439
TI  - InterLymph hierarchical classification of lymphoid neoplasms for epidemiologic
      research based on the WHO classification (2008): update and future directions.
AB  - After publication of the updated World Health Organization (WHO) classification
      of tumors of hematopoietic and lymphoid tissues in 2008, the Pathology Working
      Group of the International Lymphoma Epidemiology Consortium (InterLymph) now
      presents an update of the hierarchical classification of lymphoid neoplasms for
      epidemiologic research based on the 2001 WHO classification, which we published
      in 2007. The updated hierarchical classification incorporates all of the major
      and provisional entities in the 2008 WHO classification, including newly defined
      entities based on age, site, certain infections, and molecular characteristics,
      as well as borderline categories, early and "in situ" lesions, disorders with
      limited capacity for clinical progression, lesions without current International
      Classification of Diseases for Oncology, 3rd Edition codes, and immunodeficiency
      associated lymphoproliferative disorders. WHO subtypes are defined in
      hierarchical groupings, with newly defined groups for small B-cell lymphomas with
      plasmacytic differentiation and for primary cutaneous T-cell lymphomas. We
      suggest approaches for applying the hierarchical classification in various
      epidemiologic settings, including strategies for dealing with multiple coexisting
      lymphoma subtypes in one patient, and cases with incomplete pathologic
      information. The pathology materials useful for state-of-the-art epidemiology
      studies are also discussed. We encourage epidemiologists to adopt the updated
      InterLymph hierarchical classification, which incorporates the most recent WHO
      entities while demonstrating their relationship to older classifications.

PMID- 20699440
TI  - Vascular remodeling of the vitelline artery initiates extravascular emergence of
      hematopoietic clusters.
AB  - The vitelline artery is a temporary structure that undergoes extensive remodeling
      during midgestation to eventually become the superior mesenteric artery (also
      called the cranial mesenteric artery, in the mouse). Here we show that, during
      this remodeling process, large clusters of hematopoietic progenitors emerge via
      extravascular budding and form structures that resemble previously described
      mesenteric blood islands. We demonstrate through fate mapping of vascular
      endothelium that these mesenteric blood islands are derived from the endothelium
      of the vitelline artery. We further show that the vitelline arterial endothelium
      and subsequent blood island structures originate from a lateral plate mesodermal
      population. Lineage tracing of the lateral plate mesoderm demonstrates
      contribution to all hemogenic vascular beds in the embryo, and eventually, all
      hematopoietic cells in the adult. The intraembryonic hematopoietic cell clusters
      contain viable, proliferative cells that exhibit hematopoietic stem cell markers
      and are able to further differentiate into myeloid and erythroid lineages.
      Vitelline artery-derived hematopoietic progenitor clusters appear between
      embryonic day 10 and embryonic day 10.75 in the caudal half of the midgut
      mesentery, but by embryonic day 11.0 are sporadically found on the cranial side
      of the midgut, thus suggesting possible extravascular migration aided by midgut
      rotation.

PMID- 20699441
TI  - Detection of EBV genomes in plasmablasts/plasma cells and non-B cells in the
      blood of most patients with EBV lymphoproliferative disorders by using Immuno
      FISH.
AB  - Epstein-Barr virus (EBV) is present in B cells in the blood of healthy people;
      few studies have looked for EBV in other cell types in blood from patients with
      lymphoproliferative disorders. We use a new technique combining immunofluorescent
      cell-surface staining and fluorescent in situ hybridization to quantify both EBV
      copy number per cell and cell types in blood from patients with high EBV DNA
      loads. In addition to CD20(+) B cells, EBV was present in plasmablast/plasma
      cells in the blood of 50% of patients, in monocytes or T cells in a small
      proportion of patients, and in "non-B, non-T, non-monocytes" in 69% of patients.
      The mean EBV copy number in B cells was significantly higher than in
      plasmablast/plasma cells. There was no correlation between EBV load and virus
      copy number per cell. Although we detected CD21, the EBV B-cell receptor, on EBV
      infected B cells, we could not detect it on virus-infected T cells. These
      findings expand the range of cell types infected in the blood. Determining the
      number of EBV genomes per cell and the type of cells infected in patients with
      high EBV loads may provide additional prognostic information for the development
      of EBV lymphoproliferative diseases.

PMID- 20699442
TI  - Dendritic cells modulate platelet activity in IVIg-mediated amelioration of ITP
      in mice.
AB  - Intravenous immunoglobulin (IVIg) is an effective treatment against immune
      thrombocytopenia (ITP). Previous studies suggested that IVIg exerts this
      ameliorative role through 2 different leukocyte subsets. Dendritic cells (DCs)
      modulate the immunosuppression in an adoptive cell transfer model, and phagocytes
      up-regulate their inhibitory IgG Fc receptors (FcgammaR)IIB expression and
      thereby ameliorate the inflammatory response and platelet clearance. However,
      whether or not regulatory mechanisms exist among DCs, phagocytes, and platelets
      is still largely unknown. In this study we present findings that IVIg-primed
      splenic CD11c(+) DCs (IVIg-DCs) primarily mediate their anti-inflammatory effects
      at the level of the platelet rather than the phagocyte. IVIg-DCs did not
      ameliorate ITP in Fcgr2b(-/-), Fcgr3(-/-), nor P-Selp(-/-) mice, implicating the
      potential involvement of these pathways in IVIg action. As platelets are a
      component of DC regulatory circuits, these findings may suggest an alternative
      perspective for the use of IVIg treatment.

PMID- 20699443
TI  - Body mass index and survival after in-hospital cardiac arrest.
AB  - BACKGROUND: The quality and effectiveness of resuscitation processes may be
      influenced by the patient's body mass index (BMI); however, the relationship
      between BMI and survival after in-hospital cardiac arrest has not been previously
      studied. METHODS AND RESULTS: We evaluated 21 237 adult patients with an in
      hospital cardiac arrest within the National Registry for Cardiopulmonary
      Resuscitation (NRCPR). We examined the association between BMI (classified as
      underweight [<18.5 kg/m(2)], normal [18.5 to 24.9 kg/m(2)], overweight [25.0 to
      29.9 kg/m(2)], obese [30.0 to 34.9 kg/m(2)], and very obese [>=35.0 kg/m(2)]) and
      survival to hospital discharge using multivariable logistic regression, after
      stratifying arrests by rhythm type and adjusting for patient characteristics. Of
      4499 patients with ventricular fibrillation or pulseless ventricular tachycardia
      as initial rhythm, 1825 (40.6%) survived to discharge. After multivariable
      adjustment, compared with overweight patients, underweight (odds ratio [OR],
      0.59; 95% confidence interval [CI], 0.41 to 0.84; P=0.003), normal weight (OR,
      0.75; 95% CI, 0.63 to 0.89; P<0.001), and very obese (OR, 0.78; 95% CI, 0.63 to
      0.96; P=0.02) had lower rates of survival, whereas obese patients had similar
      rates of survival (OR, 0.87; 95% CI, 0.72 to 1.06; P=0.17). In contrast, of 16
      738 patients with arrests caused by asystole or pulseless electric activity, only
      2501 (14.9%) survived. After multivariable adjustment, all BMI groups had similar
      rates of survival except underweight patients (OR, 0.67; 95% CI, 0.54 to 0.82;
      P<0.001). CONCLUSIONS: For cardiac arrest caused by shockable rhythms,
      underweight, normal weight, and very obese patients had lower rates of survival
      to discharge. In contrast, for cardiac arrest caused by nonshockable rhythms,
      survival to discharge was similar across BMI groups except for underweight
      patients. Future studies are needed to clarify the extent to which BMI affects
      the quality and effectiveness of resuscitation measures.

PMID- 20699445
TI  - The cover. Nude in a wood.

PMID- 20699446
TI  - A piece of my mind. Maintenance.

PMID- 20699447
TI  - Experts focus on identifying, mitigating potential health effects of Gulf oil
      leak.

PMID- 20699448
TI  - Targeted therapies take aim against lung cancer and melanoma.

PMID- 20699449
TI  - H1N1 influenza virus reassorting in pigs, poses unknown risk to human health.

PMID- 20699450
TI  - IOM advises FDA on ethics in postmarket safety trials.

PMID- 20699451
TI  - B-vitamin therapy for diabetic nephropathy.

PMID- 20699444
TI  - Body mass index and risk of stroke and myocardial infarction in a relatively lean
      population: meta-analysis of 16 Japanese cohorts using individual data.
AB  - BACKGROUND: The association of overweight/obesity with the incidence of
      cardiovascular diseases, especially stroke, has not been comprehensively examined
      in relatively lean populations in which stroke is more prevalent than coronary
      heart disease. METHODS AND RESULTS: Pooled individual data from 16 Japanese
      cohorts comprising 45 235 participants ages 40 to 89 years without previous
      history of cardiovascular disease were studied. During follow-up, 1113 incident
      strokes and 190 myocardial infarctions were identified. At baseline, mean ages of
      men and women were 55.4 and 56.5 years and mean body mass indices (BMI) were 23.0
      and 23.4 kg/m(2), respectively. Compared with those with BMI <21.0, incidence
      rates of cerebral infarction in subjects with BMI >= 27.5 were significantly
      elevated in both men (hazard ratio, 1.81; 95% confidence interval [CI], 1.28 to
      2.56) and women (hazard ratio, 1.65; 95% CI, 1.23 to 2.21), adjusted for age,
      smoking, and drinking habit. Incidence of cerebral hemorrhage was also associated
      positively with BMI in both men (hazard ratio, 2.51; 95% CI, 1.21 to 5.20) and
      women (hazard ratio, 1.98; 95% CI, 1.12 to 3.52). Adjustment for systolic blood
      pressure, a mediating factor, significantly attenuated most BMI association with
      stroke in both sexes. For myocardial infarction, the hazard ratio was 3.16 (95%
      CI, 1.66 to 6.01) for BMI 27.5 or greater versus less than 21.0 only in men,
      which appeared partly mediated by total cholesterol and SBP. CONCLUSIONS:
      Overweight/obesity was associated with an increased risk of cerebral infarction
      and hemorrhage in men and women and myocardial infarction in men. Weight control
      may have the potential to prevent both stroke and myocardial infarction in Japan.

PMID- 20699452
TI  - B-vitamin therapy for diabetic nephropathy.

PMID- 20699453
TI  - Association between maternal height and childhood outcomes.

PMID- 20699454
TI  - Diagnostic testing for celiac disease.

PMID- 20699455
TI  - Health care-associated invasive MRSA infections, 2005-2008.
AB  - CONTEXT: Methicillin-resistant Staphylococcus aureus (MRSA) is a pathogen of
      public health importance; MRSA prevention programs that may affect MRSA
      transmission and infection are increasingly common in health care settings.
      Whether there have been changes in MRSA infection incidence as these programs
      become established is unknown; however, recent data have shown that rates of MRSA
      bloodstream infections (BSIs) in intensive care units are decreasing. OBJECTIVE:
      To describe changes in rates of invasive health care-associated MRSA infections
      from 2005 through 2008 among residents of 9 US metropolitan areas. DESIGN,
      SETTING, AND PARTICIPANTS: Active, population-based surveillance for invasive
      MRSA in 9 metropolitan areas covering a population of approximately 15 million
      persons. All reports of laboratory-identified episodes of invasive (from a
      normally sterile body site) MRSA infections from 2005 through 2008 were evaluated
      and classified based on the setting of the positive culture and the presence or
      absence of health care exposures. Health care-associated infections (ie, hospital
      onset and health care-associated community-onset), which made up 82% of the total
      infections, were included in this analysis. MAIN OUTCOME MEASURES: Change in
      incidence of invasive health care-associated MRSA infections and health care
      associated MRSA BSIs using population of the catchment area as the denominator.
      RESULTS: From 2005 through 2008, there were 21,503 episodes of invasive MRSA
      infection; 17,508 were health care associated. Of these, 15,458 were MRSA BSIs.
      The incidence rate of hospital-onset invasive MRSA infections was 1.02 per 10,000
      population in 2005 and decreased 9.4% per year (95% confidence interval [CI],
      14.7% to 3.8%; P = .005), and the incidence of health care-associated community
      onset infections was 2.20 per 10,000 population in 2005 and decreased 5.7% per
      year (95% CI, 9.7% to 1.6%; P = .01). The decrease was most prominent for the
      subset of infections with BSIs (hospital-onset: -11.2%; 95% CI -15.9% to -6.3%;
      health care-associated community-onset: -6.6%; 95% CI -9.5% to -3.7%).
      CONCLUSION: Over the 4-year period from 2005 through 2008 in 9 diverse
      metropolitan areas, rates of invasive health care-associated MRSA infections
      decreased among patients with health care-associated infections that began in the
      community and also decreased among those with hospital-onset invasive disease.

PMID- 20699456
TI  - Prevalence of diabetic retinopathy in the United States, 2005-2008.
AB  - CONTEXT: The prevalence of diabetes in the United States has increased. People
      with diabetes are at risk for diabetic retinopathy. No recent national population
      based estimate of the prevalence and severity of diabetic retinopathy exists.
      OBJECTIVES: To describe the prevalence and risk factors of diabetic retinopathy
      among US adults with diabetes aged 40 years and older. DESIGN, SETTING, AND
      PARTICIPANTS: Analysis of a cross-sectional, nationally representative sample of
      the National Health and Nutrition Examination Survey 2005-2008 (N = 1006).
      Diabetes was defined as a self-report of a previous diagnosis of the disease
      (excluding gestational diabetes mellitus) or glycated hemoglobin A(1c) of 6.5% or
      greater. Two fundus photographs were taken of each eye with a digital
      nonmydriatic camera and were graded using the Airlie House classification scheme
      and the Early Treatment Diabetic Retinopathy Study severity scale. Prevalence
      estimates were weighted to represent the civilian, noninstitutionalized US
      population aged 40 years and older. MAIN OUTCOME MEASUREMENTS: Diabetic
      retinopathy and vision-threatening diabetic retinopathy. RESULTS: The estimated
      prevalence of diabetic retinopathy and vision-threatening diabetic retinopathy
      was 28.5% (95% confidence interval [CI], 24.9%-32.5%) and 4.4% (95% CI, 3.5%
      5.7%) among US adults with diabetes, respectively. Diabetic retinopathy was
      slightly more prevalent among men than women with diabetes (31.6%; 95% CI, 26.8%
      36.8%; vs 25.7%; 95% CI, 21.7%-30.1%; P = .04). Non-Hispanic black individuals
      had a higher crude prevalence than non-Hispanic white individuals of diabetic
      retinopathy (38.8%; 95% CI, 31.9%-46.1%; vs 26.4%; 95% CI, 21.4%-32.2%; P = .01)
      and vision-threatening diabetic retinopathy (9.3%; 95% CI, 5.9%-14.4%; vs 3.2%;
      95% CI, 2.0%-5.1%; P = .01). Male sex was independently associated with the
      presence of diabetic retinopathy (odds ratio [OR], 2.07; 95% CI, 1.39-3.10), as
      well as higher hemoglobin A(1c) level (OR, 1.45; 95% CI, 1.20-1.75), longer
      duration of diabetes (OR, 1.06 per year duration; 95% CI, 1.03-1.10), insulin use
      (OR, 3.23; 95% CI, 1.99-5.26), and higher systolic blood pressure (OR, 1.03 per
      mm Hg; 95% CI, 1.02-1.03). CONCLUSION: In a nationally representative sample of
      US adults with diabetes aged 40 years and older, the prevalence of diabetic
      retinopathy and vision-threatening diabetic retinopathy was high, especially
      among Non-Hispanic black individuals.

PMID- 20699457
TI  - Exposure to oral bisphosphonates and risk of esophageal cancer.
AB  - CONTEXT: Use of oral bisphosphonates has increased dramatically in the United
      States and elsewhere. Esophagitis is a known adverse effect of bisphosphonate
      use, and recent reports suggest a link between bisphosphonate use and esophageal
      cancer, but this has not been robustly investigated. OBJECTIVE: To investigate
      the association between bisphosphonate use and esophageal cancer. DESIGN,
      SETTING, AND PARTICIPANTS: Data were extracted from the UK General Practice
      Research Database to compare the incidence of esophageal and gastric cancer in a
      cohort of patients treated with oral bisphosphonates between January 1996 and
      December 2006 with incidence in a control cohort. Cancers were identified from
      relevant Read/Oxford Medical Information System codes in the patient's clinical
      files. Cox proportional hazards modeling was used to calculate hazard ratios and
      95% confidence intervals for risk of esophageal and gastric cancer in
      bisphosphonate users compared with nonusers, with adjustment for potential
      confounders. MAIN OUTCOME MEASURE: Hazard ratio for the risk of esophageal and
      gastric cancer in the bisphosphonate users compared with the bisphosphonate
      nonusers. RESULTS: Mean follow-up time was 4.5 and 4.4 years in the
      bisphosphonate and control cohorts, respectively. Excluding patients with less
      than 6 months' follow-up, there were 41 826 members in each cohort (81% women;
      mean age, 70.0 (SD, 11.4) years). One hundred sixteen esophageal or gastric
      cancers (79 esophageal) occurred in the bisphosphonate cohort and 115 (72
      esophageal) in the control cohort. The incidence of esophageal and gastric cancer
      combined was 0.7 per 1000 person-years of risk in both the bisphosphonate and
      control cohorts; the incidence of esophageal cancer alone in the bisphosphonate
      and control cohorts was 0.48 and 0.44 per 1000 person-years of risk,
      respectively. There was no difference in risk of esophageal and gastric cancer
      combined between the cohorts for any bisphosphonate use (adjusted hazard ratio,
      0.96 [95% confidence interval, 0.74-1.25]) or risk of esophageal cancer only
      (adjusted hazard ratio, 1.07 [95% confidence interval, 0.77-1.49]). There also
      was no difference in risk of esophageal or gastric cancer by duration of
      bisphosphonate intake. CONCLUSION: Among patients in the UK General Practice
      Research Database, the use of oral bisphosphonates was not significantly
      associated with incident esophageal or gastric cancer.

PMID- 20699458
TI  - Trends and characteristics of US emergency department visits, 1997-2007.
AB  - CONTEXT: The potential effects of increasing numbers of uninsured and
      underinsured persons on US emergency departments (EDs) is a concern for the
      health care safety net. OBJECTIVE: To describe the changes in ED visits that
      occurred from 1997 through 2007 in the adult and pediatric US populations by
      sociodemographic group, designation of safety-net ED, and trends in ambulatory
      care-sensitive conditions. DESIGN, SETTING, AND PARTICIPANTS: Publicly available
      ED visit data from the National Hospital Ambulatory Medical Care Survey (NHAMCS)
      from 1997 through 2007 were stratified by age, sex, race, ethnicity, insurance
      status, safety-net hospital classification, triage category, and disposition.
      Codes from the International Classification of Diseases, Ninth Revision (ICD-9),
      were used to extract visits related to ambulatory care-sensitive conditions.
      Visit rates were calculated using annual US Census estimates. MAIN OUTCOME
      MEASURES: Total annual visits to US EDs and ED visit rates for population
      subgroups. RESULTS: Between 1997 and 2007, ED visit rates increased from 352.8 to
      390.5 per 1000 persons (rate difference, 37.7; 95% confidence interval [CI], 
      51.1 to 126.5; P = .001 for trend); the increase in total annual ED visits was
      almost double of what would be expected from population growth. Adults with
      Medicaid accounted for most of the increase in ED visits; the visit rate
      increased from 693.9 to 947.2 visits per 1000 enrollees between 1999 and 2007
      (rate difference, 253.3; 95% CI, 41.1 to 465.5; P = .001 for trend). Although ED
      visit rates for adults with ambulatory care-sensitive conditions remained stable,
      ED visit rates among adults with Medicaid increased from 66.4 in 1999 to 83.9 in
      2007 (rate difference, 17.5; 95% CI, -5.8 to 40.8; P = .007 for trend). The
      number of facilities qualifying as safety-net EDs increased from 1770 in 2000 to
      2489 in 2007. CONCLUSION: These findings indicate that ED visit rates have
      increased from 1997 to 2007 and that EDs are increasingly serving as the safety
      net for medically underserved patients, particularly adults with Medicaid.

PMID- 20699459
TI  - A 29-year-old woman with flu-like symptoms: review of influenza diagnosis and
      treatment.
AB  - Peaks of seasonal influenza activity occur annually in many countries, resulting
      in significant morbidity and mortality. Using the case of Ms R, a 29-year-old
      woman who presented with acute onset of respiratory symptoms and was evaluated
      for influenza, considerations regarding symptoms and signs, evaluation,
      treatment, and prevention of influenza are discussed. Symptoms of influenza can
      be similar to those of other respiratory viruses, making diagnosis challenging.
      Laboratory testing should be reserved for patients who are seriously ill or for
      whom test results may affect management or have public health implications. For
      most cases of influenza, treatment is supportive and specific antiviral
      medication is not needed. Annual vaccination is the most effective way to prevent
      infection. Educating patients on practical steps to reduce the spread of
      influenza in the community is critical.

PMID- 20699460
TI  - Future of the safety net under health reform.

PMID- 20699461
TI  - Dietary guidelines in the 21st century--a time for food.

PMID- 20699462
TI  - Evaluation of comparative treatment trials: assessing clinical benefits and risks
      for patients, rather than statistical effects on measures.

PMID- 20699463
TI  - Should sensitive information from clinical trials be included in electronic
      medical records?

PMID- 20699464
TI  - Decline in invasive MRSA infection: where to go from here?

PMID- 20699465
TI  - JAMA patient page. Esophageal cancer.

PMID- 20699466
TI  - Sustainability in biomedical research.

PMID- 20699467
TI  - The role of kisspeptin signaling in reproduction.
AB  - Kisspeptins are a group of peptides that stimulate GnRH release and are required
      for puberty and maintenance of normal reproductive function. This review focuses
      on our understanding of the way in which kisspeptin signaling regulates mammalian
      fertility and how they act as central integrators of different hormonal and
      physiological signals.

PMID- 20699468
TI  - Pathways for cytokine secretion.
AB  - Cytokine secretion is a widely studied process, although little is known
      regarding the specific mechanisms that regulate cytokine release. Recent findings
      have shed light on some of the precise molecular pathways that regulate the
      packaging of newly synthesized cytokines from immune cells. These findings begin
      to elucidate pathways and mechanisms that underpin cytokine release in all cells.
      In this article, we review the highlights of some of these novel discoveries.

PMID- 20699469
TI  - The role of endocannabinoid signaling in motor control.
AB  - Cannabinoid receptors and endocannabinoid signaling are distributed throughout
      the rostrocaudal neuraxis. Retrograde signaling via endocannabinoid mediates
      synaptic plasticity in many regions in the central nervous system. Here, we
      review the role of endocannabinoid signaling in different parts of the vertebrate
      motor system from networks responsible for the execution of movement to planning
      centers in the basal ganglia and cortex. The ubiquity of endocannabinoid-mediated
      plasticity suggests that it plays an important role in producing motion from
      defined circuitries and also for reconfiguring networks to learn new motor
      skills. The long-term plasticity induced by endocannabinoids may provide a long
      term buffer that stabilizes the organization of motor circuits and their
      activity.

PMID- 20699470
TI  - Epithelial pathways in choroid plexus electrolyte transport.
AB  - A stable intraventricular milieu is crucial for maintaining normal neuronal
      function. The choroid plexus epithelium produces the cerebrospinal fluid and in
      doing so influences the chemical composition of the interstitial fluid of the
      brain. Here, we review the molecular pathways involved in transport of the
      electrolytes Na+, K+, Cl-, and HCO3(-)across the choroid plexus epithelium.

PMID- 20699471
TI  - A gene for speed: the emerging role of alpha-actinin-3 in muscle metabolism.
AB  - A common polymorphism (R577X) in the ACTN3 gene results in complete deficiency of
      alpha-actinin-3 protein in approximately 16% of humans worldwide. The presence of
      alpha-actinin-3 protein is associated with improved sprint/power performance in
      athletes and the general population. Despite this, there is evidence that the
      null genotype XX has been acted on by recent positive selection, likely due to
      its emerging role in the regulation of muscle metabolism. alpha-Actinin-3
      deficiency reduces the activity of glycogen phosphorylase and results in a
      fundamental shift toward more oxidative pathways of energy utilization.

PMID- 20699473
TI  - B cell receptor signaling: picky about PI3Ks.
AB  - The B cell receptor (BCR) and the pre-BCR control cell fate at many stages of B
      cell development, survival, and antigen response. Most of these processes require
      the activation of phosphatidylinositol 3-kinase (PI3K). Previous work has pointed
      to p110delta as the key catalytic isoform of PI3K for many B cell responses. A
      study of mice with different combinations of PI3K mutations confirms the central
      role of p110delta in agonist-mediated signaling, while identifying an unexpected
      function for the p110alpha isoform in tonic signaling by the pre-BCR and mature
      BCR.

PMID- 20699474
TI  - Trafficking, acidification, and growth factor signaling.
AB  - Wnt and Notch signaling pathways play key roles in development and disease.
      Despite great progress, the mechanism of signal transduction of their receptor
      ligand complexes still holds surprises. For example, in both pathways,
      endocytosis is required for downstream signaling, but the mechanism by which
      endocytosis permits signaling is still unknown. New evidence indicates that
      endocytosis is required for the receptor-ligand complex to reach an acidified
      vesicular compartment. In turn, enzymes responsible for acidification are
      essential for Notch and Wnt signaling and also directly interact with the
      receptors. These findings raise new questions concerning the mechanism by which
      low pH promotes signal transduction and may open new possibilities for
      therapeutic intervention through the targeting of acidifying enzymes.

PMID- 20699475
TI  - The PI3K isoforms p110alpha and p110delta are essential for pre-B cell receptor
      signaling and B cell development.
AB  - B cell development is controlled by a series of checkpoints that ensure that the
      immunoglobulin (Ig)-encoding genes produce a functional B cell receptor (BCR) and
      antibodies. As part of this process, recombination-activating gene (Rag) proteins
      regulate the in-frame assembly of the Ig-encoding genes. The BCR consists of Ig
      proteins in complex with the immunoreceptor tyrosine-based activation motif
      (ITAM)-containing Igalpha and Igbeta chains. Whereas the activation of the
      tyrosine kinases Src and Syk is essential for BCR signaling, the pathways that
      act downstream of these kinases are incompletely defined. Previous work has
      revealed a key role for the p110delta isoform of phosphatidylinositol 3-kinase
      (PI3K) in agonist-induced BCR signaling; however, early B cell development and
      mature B cell survival, which depend on agonist-independent or "tonic" BCR
      signaling, are not substantially affected by a deficiency in p110delta. Here, we
      show that p110alpha, but not p110beta, compensated in the absence of p110delta to
      promote early B cell development in the bone marrow and B cell survival in the
      spleen. In the absence of both p110alpha and p110delta activities, pre-BCR
      signaling failed to suppress the production of Rag proteins and to promote
      developmental progression of B cell progenitors. Unlike p110delta, however,
      p110alpha did not contribute to agonist-induced BCR signaling. These studies
      indicate that either p110alpha or p110delta can mediate tonic signaling from the
      BCR, but only p110delta can contribute to antigen-dependent activation of B
      cells.

PMID- 20699476
TI  - The extracellular matrix and disease: An interview with Zena Werb. Interviewed by
      Kristin H. Kain.

PMID- 20699477
TI  - Dictyostelium possesses highly diverged presenilin/gamma-secretase that regulates
      growth and cell-fate specification and can accurately process human APP: a system
      for functional studies of the presenilin/gamma-secretase complex.
AB  - Presenilin (PS) is the catalytic moiety of the gamma-secretase complex. PS and
      other gamma-secretase components are well conserved among metazoa, but their
      presence and function in more-distant species are not resolved. Because
      inappropriate gamma-secretase processing of amyloid precursor protein (APP) in
      humans is associated with familial Alzheimer's disease, understanding essential
      elements within each gamma-secretase component is crucial to functional studies.
      Diverged proteins have been identified in primitive plants but experiments have
      failed to demonstrate gamma-secretase activity. We have identified highly
      diverged orthologs for each gamma-secretase component in the ancient eukaryote
      Dictyostelium, which lacks equivalents of APP, Notch and other characterized
      PS/gamma-secretase substrates. We show that wild-type (WT) Dictyostelium is
      capable of amyloidogenic processing of ectopically expressed human APP to
      generate amyloid-beta peptides Abeta(40) and Abeta(42); strains deficient in
      gamma-secretase cannot produce Abeta peptides but accumulate processed
      intermediates of APP that co-migrate with the C-terminal fragments alpha- and
      beta-CTF of APP that are found in mammalian cells. We further demonstrate that
      Dictyostelium requires PS for phagocytosis and cell-fate specification in a cell
      autonomous manner, and show that regulation of phagocytosis requires an active
      gamma-secretase, a pathway suggested, but not proven, to occur in mammalian and
      Drosophila cells. Our results indicate that PS signaling is an ancient process
      that arose prior to metazoan radiation, perhaps independently of Notch.
      Dictyostelium might serve to identify novel PS/gamma-secretase signaling targets
      and provide a unique system for high-throughput screening of small-molecule
      libraries to select new therapeutic targets for diseases associated with this
      pathway.

PMID- 20699478
TI  - Invertebrate insights into autism.

PMID- 20699479
TI  - Airway basal stem cells: a perspective on their roles in epithelial homeostasis
      and remodeling.
AB  - The small airways of the human lung undergo pathological changes in pulmonary
      disorders, such as chronic obstructive pulmonary disease (COPD), asthma,
      bronchiolitis obliterans and cystic fibrosis. These clinical problems impose huge
      personal and societal healthcare burdens. The changes, termed 'pathological
      airway remodeling', affect the epithelium, the underlying mesenchyme and the
      reciprocal trophic interactions that occur between these tissues. Most of the
      normal human airway is lined by a pseudostratified epithelium of ciliated cells,
      secretory cells and 6-30% basal cells, the proportion of which varies along the
      proximal-distal axis. Epithelial abnormalities range from hypoplasia (failure to
      differentiate) to basal- and goblet-cell hyperplasia, squamous- and goblet-cell
      metaplasia, dysplasia and malignant transformation. Mesenchymal alterations
      include thickening of the basal lamina, smooth muscle hyperplasia, fibrosis and
      inflammatory cell accumulation. Paradoxically, given the prevalence and
      importance of airway remodeling in lung disease, its etiology is poorly
      understood. This is due, in part, to a lack of basic knowledge of the mechanisms
      that regulate the differentiation, maintenance and repair of the airway
      epithelium. Specifically, little is known about the proliferation and
      differentiation of basal cells, a multipotent stem cell population of the
      pseudostratified airway epithelium. This Perspective summarizes what we know, and
      what we need to know, about airway basal cells to evaluate their contributions to
      normal and abnormal airway remodeling. We contend that exploiting well-described
      model systems using both human airway epithelial cells and the pseudostratified
      epithelium of the genetically tractable mouse trachea will enable crucial
      discoveries regarding the pathogenesis of airway disease.

PMID- 20699480
TI  - Disease-specific, neurosphere-derived cells as models for brain disorders.
AB  - There is a pressing need for patient-derived cell models of brain diseases that
      are relevant and robust enough to produce the large quantities of cells required
      for molecular and functional analyses. We describe here a new cell model based on
      patient-derived cells from the human olfactory mucosa, the organ of smell, which
      regenerates throughout life from neural stem cells. Olfactory mucosa biopsies
      were obtained from healthy controls and patients with either schizophrenia, a
      neurodevelopmental psychiatric disorder, or Parkinson's disease, a
      neurodegenerative disease. Biopsies were dissociated and grown as neurospheres in
      defined medium. Neurosphere-derived cell lines were grown in serum-containing
      medium as adherent monolayers and stored frozen. By comparing 42 patient and
      control cell lines we demonstrated significant disease-specific alterations in
      gene expression, protein expression and cell function, including dysregulated
      neurodevelopmental pathways in schizophrenia and dysregulated mitochondrial
      function, oxidative stress and xenobiotic metabolism in Parkinson's disease. The
      study has identified new candidate genes and cell pathways for future
      investigation. Fibroblasts from schizophrenia patients did not show these
      differences. Olfactory neurosphere-derived cells have many advantages over
      embryonic stem cells and induced pluripotent stem cells as models for brain
      diseases. They do not require genetic reprogramming and they can be obtained from
      adults with complex genetic diseases. They will be useful for understanding
      disease aetiology, for diagnostics and for drug discovery.

PMID- 20699482
TI  - Charge-selective transport of organic and protein analytes through synthetic
      nanochannels.
AB  - We present an experimental demonstration of a synthetic nanoporous membrane
      suitable for charge-selective transport of ionic species. The surfaces and walls
      of synthetic nanochannels, fabricated in heavy ion-tracked polyethylene
      terephthalate membranes are negatively charged due to the presence of carboxylate
      moieties. These nanofilters discriminate and gate the transport of cations while
      inhibiting the passage of anions. The permselectivity of these membranes is
      reversed by converting the carboxylic moieties into terminated amino groups. The
      positively charged (aminated) membranes facilitate the transport of anions. Based
      on the same principle, charged biomolecules (bovine serum albumin and lysozyme)
      are successfully filtered through these membranes. These membranes also exhibit
      the phenomenon of ion concentration polarization.

PMID- 20699483
TI  - Strain effects on the SERS enhancements for spherical silver nanoparticles.
AB  - We demonstrate in the present work through the utilization of classical Mie
      scattering theory in conjunction with a radiation damping and dynamic
      depolarization-corrected electrostatic approximation the significant effect that
      mechanical strain has on the optical properties of spherical silver
      nanoparticles. Through appropriate modifications of the bulk dielectric
      functions, we find that the application of tensile strain generates significant
      enhancements in the local electric field for the silver nanoparticles, leading to
      large SERS enhancements of more than 300% compared to bulk, unstrained
      nanoparticles when a 5% tensile strain is applied. While the strain-induced SERS
      enhancements are found to be strongest for nanoparticle diameters where radiation
      damping effects are minimized, we find that the surface plasmon resonance
      wavelengths are relatively unchanged by mechanical strain, and that the various
      measures of the far field optical efficiencies (absorption, scattering,
      extinction) can be enhanced by up to 150% through the application of tensile
      strain. The present findings indicate the opportunity to actively engineer and
      enhance the optical properties of silver nanoparticles through the application of
      mechanical deformation.

PMID- 20699484
TI  - Vibration and symmetry-breaking of boron nitride nanotubes.
AB  - The unique features of axial, torsional, transverse and radial breathing
      vibrations are captured for armchair and zigzag singlewalled boron nitride
      nanotubes (BNNTs) based on molecular mechanics simulations and continuum
      mechanics theories. Equivalent Young's modulus 1 TPa and shear modulus 0.4 TPa
      are obtained independent of the chirality of BNNTs. In particular, a distorted
      optimized structure is observed for the first time for BNNTs with sufficiently
      large diameter and length. It is found that the deformed structures result in
      behaviours of BNNTs deviating from those of classical columns/beams. Such
      symmetry-breaking could also exert significant impacts on the structural
      instability (buckling) and electronic properties of BNNTs that are sensitive to
      the structural symmetry.

PMID- 20699485
TI  - Formation and electrical transport properties of pentacene nanorod crystal.
AB  - The monophasic formation of an uncharted pentacene crystal, the pentacene
      nanorod, has been investigated. The restricted formation of the pentacene nanorod
      on a bare mica surface reveals a peculiar surface catalytic crystal growth mode
      of the pentacene. We demonstrated the charge transport measurements through a
      single pentacene nanorod and analyzed the data using a periodic hopping
      conduction model. The results revealed that the pentacene nanorod has a periodic
      conductive node within their one-dimensional crystal.

PMID- 20699486
TI  - Self-organized nanodot pattern fabrication using the reverse sputtering method.
AB  - We demonstrate the synthesis of high density periodic 2D nanodot patterns using
      reverse sputtering in magnetron sputtering equipment on a single crystal Si
      substrate and sputter-deposited Si-thin film. In this etching process, a minute
      amount of Ta is supplied by DC sputtering or splashing from the substrate holder
      surface. STEM, EDX, TEM and XPS analyses confirmed preferentially localized Ta
      silicide in the nanodots. The nanodot pattern formation is attributed to the
      repeated adsorption and desorption of Ta and Si molecules forming Ta-silicide,
      and its segregation with self-organization. We also discuss power and time
      dependence of the nanodot pattern sizes and hole structure formation as a side
      effect. This simple process is conducted at room temperature and makes use of an
      extremely simple setup. Our result promises a significant improvement in the
      productivity of quantum dot devices and has the potential to trigger their
      worldwide spread.

PMID- 20699487
TI  - Fluorescent sensing of colloidal CePO4:Tb nanorods for rapid, ultrasensitive and
      selective detection of vitamin C.
AB  - Vitamin C is an essential biological molecule for living organisms. The detection
      of vitamin C is always required due to its wide use in chemical, biological and
      pharmaceutical engineering. Here, we established a novel sensing system for
      rapid, ultrasensitive and highly selective detection of vitamin C based on a
      'turn-on' fluorescent method. The turn-on fluorescent sensing system was built up
      of a colloidal CePO(4):Tb nanocrystalline solution with its fluorescence quenched
      by KMnO(4). The addition of vitamin C leads to a linear increase of fluorescence.
      The sensing principle of nanocrystalline CePO(4):Tb is based on a redox reaction
      via simply modulating the surface chemistry of nanocrystals. Our present sensing
      system for vitamin C exhibits a rapid response rate of less than 2 min, and
      highly selective and ultrasensitive detection with a detection limit of 108 nM,
      which is two orders of magnitude lower than that acquired by previously reported
      methods. The repeated reversibility of fluorescence quenching/recovery with time
      revealed a high reproducibility and long-term stability of our sensing materials.
      Furthermore, our developed sensing material overcomes the disadvantages such as
      complex surface modification/immobilization and serious biotoxicity compared to
      quantum-dot-based fluorescent sensing systems.

PMID- 20699488
TI  - Evidence of low-temperature superparamagnetism in Mn3O4 nanoparticle ensembles.
AB  - Using ac-susceptibility, dc-magnetization, and transmission electron microscopy,
      we have investigated the magnetic behavior of Mn(3)O(4) nanoparticle ensembles at
      temperatures below the paramagnetic-to-ferrimagnetic transition of the title
      material (T(N) approximately equal 41 K). Our data show no evidence of the
      complex magnetic ordering exhibited by bulk Mn(3)O(4), or of a magnetic behavior
      around T(N) that has a dynamic (relaxation) origin. Instead, we find a low
      temperature (at approximately 11 K) magnetic anomaly that manifests itself as a
      peak in the out-of-phase component of the ac-susceptibility. Analysis of the
      frequency and average-particle-size dependence of the peak temperature
      demonstrates that this behavior is due to the onset of superparamagnetic
      relaxation, and not to a previously hinted at spin-glass-like transition. Indeed,
      the relative peak temperature variation per frequency decade DeltaT/TDeltalog(f)
      is 0.11, an order of magnitude larger than the value expected for collective spin
      freezing, but within the range of values observed for superparamagnetic blocking.
      Furthermore, attempts to fit the frequency f/observation time tau = 1/2pif
      dependence of the peak temperature by a power law led to parameter values
      unexpected for a spin-glass transition. On the other hand, a Vogel-Fulcher law
      tau = tau(0)exp[E(B)/k(B)(T - T(0))]-where E(B) is the energy barrier to
      magnetization reversal, k(B) is the Boltzmann constant, tau(0) and T(0) are
      constants related to the attempt frequency and the interparticle interaction
      strength-correctly describes the peak shift and yields values consistent with the
      superparamagnetic behavior of a slightly interacting system of nanoparticles. In
      addition, the peak temperature T is sensitive to minute changes in the average
      particle size (D), and scales as (T - T(0) is proportional to(D)3, another
      signature of superparamagnetic relaxation.

PMID- 20699489
TI  - Two steps forward, one step back: 4th WHO classification of myeloid neoplasms
      (2008).

PMID- 20699490
TI  - Diagnostic dilemma: diagnostic algorithm in fine needle aspiration cytology of
      mediastinal tumors.
AB  - The mediastinum harbors a mixed bag of tumors, which may create significant
      diagnostic dilemmas. These tumors have widely variable therapeutic and prognostic
      implications. Correct pre-operative cytological diagnosis may obviate the need of
      surgical excision of many of these lesions. A stepwise algorithmic approach such
      as clinical history, radiological localization, salient cytomorphology and
      ancillary test helps in correct diagnosis of these tumors. This paper discusses
      the stepwise diagnostic algorithm for fine needle aspiration cytology diagnosis
      of mediastinal tumors.

PMID- 20699491
TI  - Proliferative activity in oral pyogenic granuloma: a comparative
      immunohistochemical study.
AB  - CONTEXT: Pyogenic granuloma (PG) is one of the most common reactive vascular
      lesions in the oral mucosa, which has been divided into the lobular capillary
      hemangioma (LCH) and the non lobular type (non-LCH) as two distinct entities, on
      the basis of some investigations. AIMS: This study aims to compare the
      proliferative and angiogenic activity of two histological types of PG to
      determine whether they have two distinct types of biological behavior. SETTINGS
      AND DESIGN: In this retrospective cross-sectional study, immunostaining was
      performed on 10 cases of each type of PG. MATERIALS AND METHODS: About 4 microm
      sections were cut from formalin-fixed paraffin-embedded blocks and each specimen
      was stained with both anti-CD31 and anti-Ki-67 antibodies simultaneously.
      Labeling index (LI) was determined for both types by counting Ki-67 and CD31
      positive cells separately and simultaneously in 1000 stromal and luminal cells.
      Micro vessel count (MVC), the mean number of micro vessels in five areas at
      Chi200 magnification, was also determined for both groups. STATISTICAL ANALYSIS:
      The results were statistically compared using the Mann-Whitney U-test. RESULTS:
      Ki-67 LI in LCH (5.4 +/- 2.4) was higher than non-LCH (3.9 +/- 3.9). The
      percentage of CD31 positive cells in LCH (28.5 +/- 22) was lower than non-LCH
      (37.1 +/- 20.8) and simultaneously immunostaining for both markers in LCH type
      (2.4 +/- 2.1) was higher than non-LCH (1.2 +/- 1). The MVC was approximately
      77.35 +/- 34.6 and 82.6 +/- 42.7 in the lobular areas of LCH and central areas of
      non-LCH PG, respectively. These differences were not statistically significant.
      CONCLUSIONS: These results demonstrate a higher proliferation activity in
      endothelial cells of LCH PG than in non-LCH.

PMID- 20699492
TI  - Comparison of clinical, biochemical and histological features of alcoholic
      steatohepatitis and non-alcoholic steatohepatitis in Asian Indian patients.
AB  - BACKGROUND: Alcoholic steatohepatitis (ASH) and non-alcoholic steatohepatitis
      (NASH) are significant forms of liver disease and may progress to end-stage liver
      disease, cirrhosis and potentially malignant complications. The most difficult
      aspect of establishing a diagnosis of NASH is distinguishing it from ASH.
      Laboratory markers such as AST, ALT and GGT lack sufficient sensitivity and
      specificity. AIM: To study the clinical, biochemical and histological differences
      between non-alcoholic steatohepatitis (NASH) and alcoholic steatohepatitis (ASH).
      MATERIALS AND METHODS: Sixty histologically confirmed cases of non-alcoholic
      steatohepatitis and 38 cases of alcoholic steatohepatitis were included in the
      study. A modified form of scoring system proposed by Yip and Burt was used to
      grade histological features of NASH and ASH. RESULTS: Mean age was 42.85 +/-
      12.36 years in ASH group and 35.07 +/- 8.06 years for NASH group. Male: Female
      ratio was 37:1 in ASH and 4:1 in NASH. The mean ALT (P = 0.012), SAP (P = 0.003),
      serum bilirubin (P = 0.001), AST/ALT ratio (P = 0.03), steatosis (P < 0.001),
      ballooning degeneration of hepatocytes (P < 0.001), portal inflammation (P <
      0.001), Mallory hyaline (P = 0.001), ductular proliferation and fibrosis (P <
      0.001) showed a significant difference between ASH and NASH cases. DISCUSSION:
      Older age, male sex, larger derangement of serum biochemistry, high serum
      bilirubin, AST/ALT > 1, more ballooning degeneration, portal inflammation,
      Mallory's hyaline, hepatocytic and ductular cholestasis, ductular proliferation
      and higher stage of fibrosis favors a diagnosis of ASH. Younger age, high ALT,
      AST/ALT < 1, higher grade of steatosis and absence of extensive neutrophilic
      portal inflammation favors a diagnosis of NASH.

PMID- 20699493
TI  - Accuracy of intra-operative frozen section consultation in south of Iran during
      four years.
AB  - BACKGROUND: Accuracy of intraoperative frozen section diagnosis is an important
      part of quality control in surgical pathology. In this study we try to evaluate
      the frozen section diagnosis in our center, a referral center in southern Iran.
      MATERIALS AND METHODS: During the four-year-period of study, all the frozen
      sections in the affiliated hospitals of Shiraz University of Medical Sciences
      were evaluated. Discrepant cases were studied to find out reasons for their
      inaccuracies. RESULTS: In the four years, 759 frozen sections have been done, 25
      of which showed discordant results. The most common site of frozen section and
      discrepancy was in central nervous system tumors. The reason for inaccuracy in
      frozen section diagnosis in 52% of cases was proved to be interpretative, 44%
      sampling error and the remainder due to lack of clinical information of the
      pathologist. CONCLUSION: Accuracy of our intraoperative consultation is
      comparable with other centers in Western countries. Most of the discrepancies can
      be prevented by providing more clinical information for the pathologist and more
      accurate sampling.

PMID- 20699495
TI  - Nuclear factor kappa-B and histopathology of chronic gastritis.
AB  - BACKGROUND: Studies suggest that nuclear factor kappa-B (NFkappaB) activation may
      be a critical event in the production of proinflammatory molecules in
      Helicobacter pylori-associated gastritis. MATERIALS AND METHODS: This study
      examines the expression and activity of NFkappaB in situ in antral biopsies of 42
      consecutive patients with immunohistochemical techniques. RESULTS: NFkappaB was
      highly expressed in the gastric epithelial cells. The number of cells showing
      activated NFkappaB correlated with the activity of gastritis (P < 0.05), a
      measure of neutrophil influx, whereas no correlation was found with the
      chronicity of inflammation, a measure of the presence of mononuclear inflammatory
      cells. There was also a strong inverse association with the presence and grade of
      atrophy. CONCLUSION: This correlation is direct evidence of the importance of
      NFkappaB dependent signal transduction for neutrophil influx in gastritis. The
      role of NFkappaB appears to be only in the initial stages of gastritis, there is
      no role for the molecule in the development of chronic inflammation or atrophy.

PMID- 20699496
TI  - Pathology of pediatric liver tumors, a single center experience from south of
      Iran.
AB  - BACKGROUND: Pediatric hepatic malignancies are rare, accounting for 1-4% of all
      solid childhood tumors. The histopathology of childhood hepatic tumors guides the
      treatment and prognosis, and is the cornerstone for precise diagnosis. Until now,
      there has been no documented study on pediatric liver tumor cases from this
      center; in this report, we show our experience about the common types of
      childhood hepatic tumors during five years (2002-2007) and compare them with
      other studies. MATERIALS AND METHODS: During five years (2002-2007), all the
      hepatic tumors of childhood (under 18 year-old) from the pathology file of Namazi
      Hospital of Shiraz University of Medical Sciences are recorded. This includes
      both resected specimens and biopsies. All the slides were reviewed and the
      pathologic diagnosis was confirmed. RESULTS: We detected 53 liver tumor cases in
      children (below 18 years of age). Among these tumors, 36 (67.9%) were malignant.
      Male to female ratio was 1.5 to 1. Hepatoblastoma was the most common liver tumor
      in this age group accounting for 22 patients (41.5%). The second most common
      primary tumor was hepatocellular carcinoma (HCC), with five patients. Another
      malignant tumor was embryonal sarcoma. Benign tumors included adenoma,
      mesenchymal hamartoma, vascular tumors, focal nodular hyperplasia, and
      inflammatory pseudo tumor. There were also seven metastatic tumors during these
      five years. CONCLUSIONS: The spectrum of hepatic tumors in children is different
      from that found in the older age group (adults) and also different in different
      populations.

PMID- 20699497
TI  - Correlation of antinuclear antibody immunofluorescence patterns with immune
      profile using line immunoassay in the Indian scenario.
AB  - BACKGROUND: Immunity status, individual response to disease and types of
      antibodies produced are well known to vary from person to person, place to place
      and probably from population to population. A broad spectrum of specific auto
      antibodies that have so far been associated with specific rheumatic diseases, as
      noted in Western literature, has been well taken as a reference standard all over
      the world. There is neither research work nor any data correlating the auto
      antibodies and their antinuclear antibody (ANA) patterns with the immunoprofile
      in the Indian population to date. AIMS: To understand a definite association
      between ANA patterns and specific antibodies in the serum in the Indian study
      population and to document similarities / differences with the West. SETTINGS AND
      DESIGN: This prospective and retrospective double blind study was undertaken on
      the South Indian population referred for ANA testing by Indirect
      Immunofluorescence method and by immunoline methods. MATERIALS AND METHODS: Serum
      samples of patients from a random South Indian population who sought medical help
      for rheumatic disease were subjected for ANA testing by indirect
      immunofluorescence (IIF) method and line immunoassay during the study period of
      27 months. Serum samples were processed in dilution of 1:100 using HEp - 2010 /
      liver biochip (Monkey) (EUROIMMUN AG). The serum samples which were further
      processed for line immunoassay were treated in 1:100 dilution on nylon strips
      coated with recombinant and purified antigens as discrete lines with plastic
      backing (EUROIMMUN AG) coated with antigens nRNP / Sm, Sm, SSA, Ro-52, SSB, Scl
      70, PM-Scl, PCNA, Jo-1, CENP-B, dsDNA, nucleosomes, histones, ribosomal protein
      P, anti-mitochondrial antibodies (AMA-M2) along with a control band. The analysis
      was done by comparing the intensity of the reaction with positive control line by
      image analysis. RESULTS: The antinuclear antibody indirect immunofluorescence
      (ANA - IIF) patterns obtained were projectable to visualize a certain spectrum of
      specific antibodies such as homogenous (45.5%) with dsDNA, nucleosomes, histones,
      SSA / Ro-52, RIB and RNP / Sm, speckled pattern (35.6%) with Sm, RNP, SSA/Ro-52,
      SSB, Sm and RIB; nucleolar pattern with Scl-70, Sm, RNP and centromere pattern
      with CENP-B. The methodology indicated that, cytoplasmic pattern noted in ANA
      also needs to be correlated with primate liver in a biochip, which should prompt
      further decision for a request for line immunoassay and it is preferable for two
      pathologists to report independently and sign out a consensus ANA report for
      better predictive value. CONCLUSIONS: As a definite correlation between the ANA
      patterns and the group of antibodies was detected by line immunoassay, one could
      predict presence of certain specific auto antibodies for a particular ANA pattern
      identified. This may restrict one from requesting for line immunoassay, which is
      expensive and economizes on the cost of laboratory investigations in a developing
      country like India. Thus, screening of sera by ANA-IIF method alone may suffice
      and probably reduce the expense of detailed immunological work-up with minimal
      loss in diagnostic accuracy. This study, the first of its kind in India, provides
      database and reference for the Indian subpopulation.

PMID- 20699498
TI  - Evaluation of the rheumatoid factors of the IgG, IgM and IgA isotypes as
      prognostic parameters for rheumatoid arthritis among Iraqi patients.
AB  - CONTEXT: Rheumatoid arthritis (RA) has a heterogeneous course, spanning from mild
      forms tending to remission and reacting well to treatment, to aggressive forms
      resistant to classical therapeutic measures. Reliable predictive parameters of
      the disease course in RA are needed. Raised levels of Rheumatoid Factors (RFs)
      are associated with RA and that this RF is found in IgM, IgA and IgG classes
      (isotypes). AIMS: To figure out the value of RF isotypes titers as predictors for
      RA processes and outcomes. MATERIALS AND METHODS: Fifty three RA patients were
      enrolled in this study. The patients were diagnosed based on ACR criteria. Blood
      sample was taken from each patient at time of attending; sera were separated
      immediately and kept frozen at -70oC until used. Disease Activity Score (DAS) was
      calculated using DAS28-3 formula. Radiographs were read by expert radiologists.
      Sandwich Enzyme-linked Immunosorbent Assay (ELISA) was used for the separate
      quantitative detection of RF of the IgG, IgM and IgA classes in serum.
      STATISTICAL ANALYSIS USED: Chi-square, Pearson's correlation coefficient and ROC
      statistical analyses was performed using SPSS version 15.0. RESULTS: Among the 53
      RA patients who were enrolled in this study, there were statistically significant
      positive correlations between the presence of radiological joint changes with
      serum levels of IgG-RF, IgM-RF and IgA-RF as measured by calculation of area
      under curve (0.772, 0.703 and 0.769, respectively). However, no correlation could
      be found between those RF isotypes with any of other disease processes and
      outcomes. CONCLUSIONS: These results may indicate the importance of the titers of
      those isotypes as good predictors of erosive RA and may reflect a causal
      relationship between their titers and joint damage during the course of RA.

PMID- 20699499
TI  - Significance of intratumoral microvessel density quantification based on
      immunohistochemical detection of PECAM-1 and vWF in colorectal carcinoma from
      Iraqi patients.
AB  - CONTEXT: Counting of newly formed microvessel may prove to be a useful tool in
      the early detection of metastatic potential and selection of patients for whom
      antiangiogenesis drugs might be beneficial. AIMS: We designed this study to
      assess the significance of microvessel quantification in colorectal cancer with
      respect to different clinicopathological variables. MATERIALS AND METHODS: Forty
      archived paraffin-embedded colorectal adenocarcinoma samples and their resection
      margins were enrolled in our study. Thin paraffin-embedded sections (3-5 m thick)
      of both tumor and resection margins were prepared for each respective biopsy and
      were used to detect endothelial cell (EC) surface expression of PECAM-1 and vWF
      by immunohistochemistry technique. STATISTICAL ANALYSIS: For the comparison
      between tumor and resection margin regarding the investigated parameters, the t
      test of significance was conducted. The association between surface expression of
      PECAM-1 and vWF along with tumor differentiation, depth of invasion and lymph
      node metastasis was performed by Chi-square (chi2 ) and ANOVA test as well as 95%
      confidence interval. On the other hand, the association between the investigated
      parameters and tumor stage as well as tumor size was performed by student t-test.
      The correlations between the two investigated parameters in respect to various
      clinicopathological parameters were calculated by correlation coefficient (r).
      Statistical significance was defined as P < 0.05. All statistical analyses were
      performed using SPSS statistical package for social and medical science version
      15.0. RESULTS: Based on the current outcome, there were significant differences
      in microvessel density based on PECAM-1 or vWF immunostaining when each tumor
      sample was compared to its respective resection margin (P < 0.001 and P < 0.001,
      respectively). In addition, tumors >or=3 mm 3 in size demonstrated a significant
      increase in their microvessel density compared to their counterparts whether
      PECAM-1 or vWF immunostaining was applied (P < 0.001 and P < 0.001,
      respectively). Moreover, when tumor samples were analyzed based on their depth of
      invasion, for intratumoral microvessel count, exclusively, vWF immunostaining
      analysis demonstrated significant differences among the three groups: submucosa
      into muscularis propria (SMP), tumor reaches serosa (SE) and tumors invade other
      organs (OR), since the latter came up with the highest microvessel count (P <
      0.05). When tumor lymph node metastases were questioned, exclusively, vWF
      immunostaining were significantly differentiated among N0, N1 and N2 groups (P <
      0.05). Concerning the possible correlations between the two investigated
      parameters in respect to various histopathological variables, both PECAM-1 and
      vWF immunostaining demonstrated significant positive correlations in tumor
      samples (r = 0.37), whereas in resection margins, these correlations were absent.
      Although, PECAM-1 and vWF immunostaining revealed significant and positive
      correlations within tumor differentiation (WD: r = 0.56, MD: r = 0.57 and PD: r =
      0.89) as well as with tumor stage (A-B: r = 0.39 and C-D: r = 0.31), still, they
      seem to correlate significantly and exclusively within SE group (r = 0.74),
      tumors <3 mm 3 in size (r = 0.66), N0 (r = 0.36) and N1 (r = 0.85) groups.
      However, PECAM-1 and vWF immunostaining revealed significant but negative
      correlation exclusively within N2 group (r = -0.38). CONCLUSION: In conclusion,
      microvessel count could be useful as a predictor for tumor metastases in patients
      with colorectal adenocarcinoma. Possible interpretations of the current outcome
      are explained thoroughly in the text.

PMID- 20699500
TI  - Nitric oxide synthase 3 and endothelin 1 immunoreactivity in pulmonary
      hypertension.
AB  - CONTEXT: Pulmonary hypertension (PH) is a serious and sometimes life-threatening
      event that occurs as a complication of various cardiopulmonary disorders, of
      which rheumatic heart disease (RHD) is an important example in our country. The
      pathogenesis of PH is a complex, multistep process in which "pulmonary
      endothelial dysfunction" (PED) is widely regarded as the central pathogenetic
      event. PED is, in turn, influenced by several local and systemic factors, of
      which nitric oxide synthase 3 (NOS3) and endothelin 1 (ET1) are 2 prime
      candidates, and are the subject of our study. AIMS: Our aim was to study the
      immunoreactivity of NOS3 and ET1 in the pulmonary vasculature of PH patients of
      various etiologies, with emphasis on RHD cases. SETTINGS AND DESIGN: A
      retrospective, autopsy-based study. SUBJECTS AND METHODS: A total of 49 autopsy
      cases (39 patients and 10 controls) were chosen for our study. Of the 39
      patients, 20 had PH secondary to RHD, whereas the remaining 19 patients had non
      RHD etiologies as the basis of their PH. Lung sections taken from all the 49
      cases were subjected to routine H and E, elastic van Gieson, and
      immunohistochemical staining (with NOS3 and ET1 separately). The intensity of
      immunostaining in all the cases and controls were then graded as focal/diffuse
      and weak/strong. RESULTS: Controls showed positivity for both NOS3 (bronchiolar
      epithelium) and ET1 (endothelium of pulmonary arteries). Characteristic changes
      of PH on H and E were seen in 14 out of 19 non-RHD cases, which matched with the
      number of ET1 positivity cases. Similarly, for the RHD cases, 14 out of 20 cases
      showed changes of PH on H and E, but only 2 cases showed mild, focal positivity
      for ET1. Surprisingly, NOS3 positivity was largely absent in both the non-RHD and
      RHD cases. CONCLUSIONS: Our study showed NOS3 negativity and ET1 positivity in
      the lung vasculature of patients with PH, a conclusion more or less in line with
      the predominant view of the other investigators in this field. But at the same
      time, our study could not conclude an unequivocal role of NOS3 in PH, whereas it
      could, in the case of ET1.

PMID- 20699501
TI  - Expression of cyclooxygenase-1 and 2 in chronic tonsillitis.
AB  - OBJECTIVES: Prostaglandins are critical mediators of inflammation and affect both
      humoral and cell-mediated immune responses. Recent findings show that T and B
      cells express COX-2 upon activation. The purpose of this study is to investigate
      the potential occurrence of COX-1 and COX-2 immunoreactivity in cases of chronic
      tonsillitis and to determine the sites of their expression. In addition, their
      expression in adult patients is compared with that in child patients. MATERIALS
      AND METHODS: Immunohistochemical techniques were used to evaluate the expression
      of the enzymes COX-1 and COX-2, in chronic tonsillitis tissue specimens from
      adults (n = 15) and children (n = 15). RESULTS: There was no staining in surface
      epithelium or reticulated crypt epithelium. COX-1 and COX-2 expressions were
      observed mainly in the intraepithelial lymphoid cells in reticulated crypt
      epithelium and subepithelial cells. Also, COX-1 and COX-2 stained cells were
      found in the germinal center. There was no difference of the expressions of COX-1
      and COX-2 among adults and children. The only significant difference noted
      between the adults and children was that, the adults had rich subepithelial
      plasma cells. CONCLUSION: Activated B and T cells express COX-1 and COX-2 in
      paraffin-embedded tissue sections of chronic tonsillitis. Further studies need to
      be performed to elucidate expression of COX enzymes and their immunologic role in
      tonsil diseases. They will play an important role in the treatment of chronic
      tonsillitis. Additional studies are warranted to study the effects of NSAIDs and
      selective COX-2 inhibitors in chronic tonsillitis.

PMID- 20699502
TI  - Primary intestinal T cell lymphomas in Indian patients--in search of enteropathic
      T cell lymphoma.
AB  - OBJECTIVE: This series of six intestinal T cell lymphomas (ITCL) attempts to
      document enteropathy-associated T cell lymphoma (EATCL) in India. MATERIALS AND
      METHODS: A total of six ITCL were selected from 170 gastrointestinal lymphomas in
      last 10 years. RESULTS: The cases studied included EATCL (4), ITCL with a CD4
      positive phenotype (1) and ITCL NK/T cell type (1). Of the four EATCL, two
      occurred in the ileum, one in right colon and one in duodenum. In three EATCL
      cases, there was history of celiac disease or lactose intolerance and
      enteropathic changes were noted in the adjacent mucosa. These tumors had
      CD3+/CD8+/CD56 (+/-)/CD4-/ Granzyme B+ immunophenotype. One EATCL was monomorphic
      small cell type (type II EATCL) with a CD3+/CD8-CD56+/CD4-/ Granzyme B+
      phenotype. EBER- ISH (Epstein Barr virus coded RNA's- in situ hybridization)
      revealed positive tumor cells in ITCL NK/T cell type and in bystander cells in
      three EATCL. CONCLUSION: ITCL are rare in Indian patients but do occur and
      comprise a mixture of the enteropathic and non-enteropathic subtypes.

PMID- 20699503
TI  - Second opinion and discrepancy in the diagnosis of soft tissue lesions at
      surgical pathology.
AB  - OBJECTIVE: To determine the frequency and magnitude of discrepancies in the
      surgical pathological diagnosis of soft tissue lesions on review and second
      opinion in a histopathology center. STUDY DESIGN: Cross-sectional, observational.
      PLACE AND DURATION OF STUDY: Department of Histopathology, Armed Forces Institute
      of Pathology, Rawalpindi, from April 2006 to May 2007. MATERIALS AND METHODS: All
      the cases of soft tissue as well as bone lesions, irrespective of age and gender,
      which were referred for second opinion or review after being reported elsewhere,
      were included in the study. A panel of antibodies of soft tissue, epithelial and
      lymphoid markers was applied according to the requirements of each case. The
      cases were categorized as category A where there was concurrence between initial
      diagnosis and diagnosis at review. Category B included cases where there was
      disagreement in the specific diagnostic entity as per WHO classifications without
      therapeutic implications. Category C was cases where the category of benign or
      malignant diagnosis remained the same but there was disagreement in the specific
      diagnosis with definite therapeutic implications. Category D had diagnosis of
      benign changed to malignant while category E had cases where diagnosis of
      malignancy was changed to a benign lesion. RESULTS: During the study period, 34
      cases of soft tissue lesions were received for review and second opinion. The
      mean age of the patients was 39 22 years and immunohistochemistry was performed
      in 21 (62%) of 34 cases. Concurrence between the review and initial diagnosis was
      seen in 18 (53%) cases (category A). Discrepancy in the diagnosis at review and
      initial consultation was seen in 16 (47%) cases. There were four (11.8%) cases
      that were placed in category B as the diagnosis of benign and malignant remained
      the same but the specific diagnostic entity was changed. Category C included
      eight (23.5%) cases where the review diagnosis changed the therapeutic modality
      despite the benign or malignant category remaining unchanged. All the cases in
      this category required immunohistochemistry as diagnosis of metastatic carcinoma
      was changed to sarcoma in two cases and diagnosis of sarcoma was changed to
      carcinoma in three cases. There was only one (2.9%) case in category D where a
      benign diagnosis was changed to malignant on review and three (8.8%) cases
      reported as malignant had a revised diagnosis of benign lesion, placing them in
      category E. CONCLUSION: In the absence of a quality assurance regulatory body to
      monitor and overlook the professional competence of practicing surgical
      pathologists, a mandatory review and second opinion should be undertaken whenever
      a major therapeutic endeavor is to be undertaken, regardless of the cost for the
      ultimate benefit of the patient.

PMID- 20699504
TI  - Peritumoral lymphatic vessel density as a prognostic parameter in endometrial
      carcinoma: an immunohistochemical study.
AB  - CONTEXT: Lymphatic invasion and nodal metastasis play a major role in the spread
      and prognosis of endometrial adenocarcinoma (EC). AIMS: In this study, we
      investigate tumor lymph-angiogenesis, detected by D2-40, as a predictive marker
      for the risk of lymph node (LN) metastasis and its relation to other prognostic
      parameters in EC. MATERIALS AND METHODS: Fifty-five cases of EC treated with
      total hysterectomy and pelvic LN dissection were reviewed. All cases were
      immunostained for D2-40. Positively stained microvessels (MV) were counted in
      densely lymphovascular foci (hotspots) at X 400 field (0.17 mm2). STATISTICAL
      ANALYSIS: Statistical analysis was performing using Chi square "X 2" test.
      RESULTS: Lymphovascular invasion was detected in 20 / 55 patients by D2-40 and 14
      / 55 by routine hematoxylin and eosin (H and E). Peritumoral lymphatic vessel
      (LV) count was significantly higher than intratumoral LV count (17 + 7 versus 5 +
      4 / 0.17 mm 2 , P < 0.01). Peritumoral D2-40 lymphovascular counts correlated
      significantly with FIGO grade (P < 0.001), lymphovascular invasion (P = 0.001)
      and LN metastases (P = 0.005). However, it showed non-significant correlation
      with peritoneal wash positivity (P = 0.830) and stage of the disease (P = 0.341).
      Intratumoral lymphovascular invasion detected by D2-40 showed significant
      correlation with LN metastases (P < 0.01). CONCLUSIONS: Our study shows that
      assessing LVD with D2-40 in the endometrial carcinoma might be a valuable
      parameter for predicting patients having an increased risk of developing of
      metastatic disease. In addition, D2-40 increases the frequency of detection of
      lymphatic invasion relative to routine H and E stain.

PMID- 20699505
TI  - Comparison of FibroTest-ActiTest with histopathology in demonstrating fibrosis
      and necroinflammatory activity in chronic hepatitis B and C.
AB  - AIMS: FibroTest and ActiTest are noninvasive tests used in determining the level
      of fibrosis and the degree of necroinflammatory activity in the liver. In our
      study, we aimed to investigate whether these tests could be alternative to liver
      biopsy. MATERIALS AND METHODS: Fifty patients were included in the study. Serum
      samples were obtained and liver needle biopsy was performed on the same day.
      Levels of fibrosis in FibroTest and levels of activity in ActiTest, both
      determined via serum biochemical markers, were compared with levels of fibrosis
      and activity in histopathological examination. For statistical analyses, Mc Nemar
      chi square test and Spearman's correlation tests were used. RESULTS: There was a
      significant positive correlation between fibrosis in biopsy and the level of
      fibrosis in FibroTest in patients with hepatitis B virus (HBV) (rho: 0.67, P <
      0.0001). However, no significant correlation was determined between the activity
      in biopsy and the degree of activity in ActiTest (rho: 0.29, P < 0.05). No
      significant correlation was determined between both fibrosis and activity
      established in biopsy and the results of FibroTest and ActiTest in the group of
      patients with hepatitis C virus (HCV) (rho: 0.22, P < 0.05 and rho: 0.15, P <
      0.05, respectively). CONCLUSION: Our results suggest that novel and safer
      noninvasive biochemical tests are needed as an alternative to histopathology in
      patients infected with HBV and HCV. Consequently, we believe that liver biopsy
      maintains its place as a gold standard in determining the histopathological
      condition of the liver.

PMID- 20699506
TI  - Significance of eosinophils in diagnosing Hashimoto's thyroiditis on fine-needle
      aspiration cytology.
AB  - BACKGROUND: Hashimoto's thyroiditis (HT) is the most common cause of
      hypothyroidism in those areas of the world where iodine levels are sufficient.
      Fine-needle aspiration cytology (FNAC) can accurately diagnose this lesion in
      most of the patients. However, a small percentage of cases may be missed due to
      inherent limitations of this procedure. Therefore, cytologic clues to increase
      sensitivity of diagnosis need to be searched for. AIMS: To assess whether an
      eosinophilic infiltration of the thyroid gland has a higher association with HT
      than colloid goiter. MATERIALS AND METHODS: The study was a case-control study.
      Smears obtained by FNAC of 50 case, each of HT (which served as cases) and
      colloid goiter (which served as controls) were observed. The number of
      eosinophils and neutrophils per high-power field (HPF) was counted in all the
      smears. The eosinophil-neutrophil ratio in the smears, diagnosed as HT, was then
      compared with that of colloid goiter using unpaired t-test. RESULTS: Smears
      diagnosed as HT was found to have a significantly higher eosinophil-neutrophil
      ratio than smears diagnosed as colloid goiter (P value 0.0001). CONCLUSION:
      Eosinophilic infiltration of the thyroid gland has higher association with
      Hashimoto thyroiditis.

PMID- 20699507
TI  - Correlation of hepatitis C RNA and serum alanine aminotransferase in hepatitis B
      and C seronegative healthy blood donors.
AB  - INTRODUCTION: Historically, serum alanine transaminase (ALT) has been used as a
      surrogate marker in the detection of hepatitis viruses in blood donors. With the
      availability of newer sensitive technologies for the detection of seroconversion,
      the value of ALT becomes questionable but continues to be used for this purpose
      with subsequent discarding of ALT elevated blood units. OBJECTIVE: The present
      study aims to evaluate the significance and cost effectiveness of ALT as a
      surrogate marker for hepatitis C virus infection in healthy asymptomatic blood
      donors who were serologically negative. MATERIALS AND METHODS: The study was
      conducted at clinical laboratory of a tertiary care hospital for a period of one
      year from November 2006 to October 2007. All donors were screened serologically
      for hepatitis B, C and HIV I and II, syphilis and malaria and those tested
      positive were excluded from further evaluation. Gender-wise reference ranges and
      minimal and markedly raised results for ALT (described respectively as one and
      two folds increase above reference range) were defined and, accordingly, donors
      were grouped into three. Two hundred seronegative blood donors were randomly
      selected from all three groups of ALT results and tested for hepatitis C nucleic
      acid through Amplicor HCV RNA test. The cost of discarding an ALT -only elevated
      blood unit was also assessed. During the study period, 25117 subjects donated
      blood. EIGHT HUNDRED AND RESULTS: Seventy two donors (3.4%) were positive for one
      or more serological tests. ALT of all donors ranged from 0-1501 U/L (Mean +/- SD;
      33.4 +/- 25.45 U/L). The donors seronegative for all disease markers were 24245
      (96.6%). Of these, 21164 (87.2%) donors had their ALT within reference range
      while 2874 (11.8%) and 207 (0.8%) of donors had minimal and markedly elevated
      results. Thus, 621 blood bags (red cells, platelets and plasma) costing $ 39200.0
      were discarded based on ALT results alone. Of 200 seronegative donors evaluated
      for hepatitis C nucleic acid, only one within markedly elevated ALT levels was
      found to be positive. The present work did not support a positive association
      between hepatitis C virus nucleic acid and elevated ALT in healthy serologically
      negative blood donors. CONCLUSION: We did not find serum ALT testing in donors as
      cost effective strategy for detection of hepatitis C virus ribonucleic acid. As
      the number of samples tested by us was small we suggest further work to evaluate
      the value of ALT levels in serologically negative donors in association with
      hepatitis C antigen and NAT testing to elucidate the true burden of disease in
      geographical regions where hepatitis C is endemic and voluntary blood donation is
      sparse.

PMID- 20699508
TI  - Prevalence and spectrum of von Willebrand disease in Eastern Uttar Pradesh.
AB  - CONTEXT: Von Willebrand disease is the most common inherited bleeding disorder
      with a prevalence of approximately 1% in the general population. Studies
      available from India are limited, showing a prevalence of approximately 10% of
      vWD amongst inherited bleeding disorders. AIMS: This study aims to know the
      prevalence and subtypes of vWD in patients presenting with various bleeding
      manifestations to university hospital. SETTINGS AND DESIGN: We investigated 840
      patients presenting with bleeding manifestations in the period from August 2004
      to August 2008 for bleeding disorders. MATERIALS AND METHODS: Tests performed for
      the diagnosis of vWD included platelet count, bleeding time (BT), prothrombin
      time (PT), activated partial thromboplastin time (APTT), Factor VIII:C assay, von
      Willebrand Factor Antigen assay and Ristocetin-induced platelet aggregation.
      RESULTS: Amongst 840 patients, 230 (27.38%) had inherited bleeding disorder. Out
      of these, 40 (17.39%) patients were identified as vWD. Type 1 in 17 (42.5%), Type
      2 in 11 (27.5%) and Type 3 vWD was present in 12 (30.0%) patients. Patients' age
      ranged from five months to 45 years, with 17 males and 23 females. Positive
      family history was seen in 12 patients (30%). Muco-cutaneous bleeding was the
      most common presentation. Menorrhagia was present in 100% women of reproductive
      age group, and hemarthrosis was seen in two male patients. CONCLUSIONS: We felt
      that Type I vWD with infrequent and mild bleeding episodes remain undiagnosed
      either because of unawareness of the disease in society or due to paucity of
      diagnostic facilities available in our country. Therefore, an awareness program
      along with enhancement of diagnostic facilities for vWD is required in our
      country to identify these patients for proper management thus avoiding
      hemorrhagic complications.

PMID- 20699509
TI  - Clinicopathologic spectrum of Waldenstrom's macroglobulinemia: a single center
      experience.
AB  - Waldenstrom's Macroglobulinemia (WM) is a B cell neoplasm characterized by
      infiltration of the bone marrow by a lymphoplasmacytic infiltrate and an IgM
      monoclonal gammopathy. We report a 15-year review of patients diagnosed with WM
      at our center. A total of 18 patients were diagnosed and treated at our center
      during the study period. Neurological symptoms were seen in almost 95% while B
      symptoms were present in almost 80% of patients. More than two-thirds of patients
      were anemic at the time of presentation and more than 90% showed bone marrow
      infiltration with lymphoplasmacytoid cells. Anemia, B symptoms, splenomegaly and
      neurological symptoms were the primary reasons in the majority of patients to
      initiate treatment. Chlorambucil was the primary treatment in more than half the
      patients followed by CVP. The median overall survival in all patients was 29
      months (range 22-81 months). WM is a rare disorder and novel therapeutic
      modalities need to be identified to improve survival in these patients.

PMID- 20699510
TI  - Serum tumor necrosis factor alpha and C-reactive protein in pediatric patients
      with sepsis and its correlation with microbiologic findings.
AB  - OBJECTIVE: To study the association of tumor necrosis factor-a (TNF-a) and C-
      reactive protein (CRP) with microbiologically documented cases of sepsis versus
      clinically documented cases of sepsis. MATERIALS AND METHODS: Seventy nine
      pediatric patients with sepsis were studied. Relevant specimens were processed
      for bacterial or fungal etiology. TNF-a was detected by enzyme immunoassay and
      CRP was detected by latex agglutination. Thirty healthy cases were included in
      the study to establish baseline TNF-alpha levels. RESULTS: Forty two (53.2%)
      patients had a microbiologically documented sepsis. Among Gram negative bacilli
      Escherichia coli was the most common isolate followed by Klebsiella spp.
      Staphylococcus aureus and Streptococcus pneumoniae predominated among the Gram
      positive cocci. Patients with a positive culture had significantly higher TNF
      alpha levels than patients with a negative culture (70 pg/ml vs. 33 pg/ml P <
      0.01). Further, pure gram negative infection correlated with significantly higher
      TNF-alpha levels than pure (P < 0.01) gram positive infection. The CRP values did
      not highlight these differences significantly. CONCLUSIONS: TNF-alpha level was
      significantly raised in patients with sepsis. TNF-a levels were raised
      significantly in culture positive cases in general and in Gram negative
      infections in particular. Serum TNF-alpha was a more sensitive marker for
      different categories of sepsis compared to CRP and microbiology culture.

PMID- 20699511
TI  - Geographical location and age affects the incidence of parasitic infestations in
      school children.
AB  - Environmental factors affect the dissemination and distribution of intestinal
      parasites in human communities. To comprehend the prevalence of parasitic
      infestation and to examine whether geographical location and age also influence
      the prevalence of infection, fecal samples from 195 school children (rural = 95;
      male = 39; female = 56) (urban = 100; male = 60; female = 40) of five age groups
      ranging from 5 to 11 years in two different socio-economic zones (rural and
      urban) were screened for specific intestinal parasites using standard
      histological techniques. Percentage incidences of parasitic species found in
      fecal wet mounts and concentrates in rural children were Entamoeba coli (25.3%),
      Giardia lamblia (17.9%), Blastocystis hominis (14.7%), Entamoeba histolytica
      (4.2%), Iodamoeba butschlii (1.1%), Hymenolepis nana (1.1%) and Ascaris
      lumbricoides (1.1%). Whereas the percentage incidences among urban children were
      E. coli (26%), A. lumbricoides (21%), B. hominis (18%), G. lamblia (14%), T.
      trichiura (8%), I. butschlii (4%) and A. duodenale (1%). Such findings may be
      related to dietary differences, living conditions and the greater use of natural
      anti-helminthic medicinal plants in rural communities. These results are
      important for both epidemiological data collection and for correlating dietary
      differences to intestinal parasitic diseases. AIMS: We chose to investigate
      whether geographical location and age affect the prevalence and distribution of
      intestinal parasites among school children from two separate regions (rural and
      urban) in areas surrounding, Chennai, Tamil Nadu, India. SETTINGS AND DESIGN: A
      study of the prevalence of parasitic infestations was undertaken among primary
      school children, in rural and urban communities around Chennai, Tamil Nadu,
      India. MATERIALS AND METHODS: Faecal sample collection, direct microscopic
      techniques, macroscopic examination and concentration techniques for identifying
      the parasites. STATISTICAL ANALYSIS USED: Percentage incidences of parasitic
      species found in faecal wet mounts and concentrates were done instead of
      statistical analyses. RESULTS: Both macroscopic and microscopic examinations of
      faecal samples revealed that the overall percentage prevalence of parasite
      species encountered in rural children were Entamoeba coli (25.3%), G. lamblia
      (17.9%), B. hominis (14.7%), Entamoeba histolytica (4.2%), I. butschlii (1.1%),
      H. nana (1.1%), Ascaris lumbricoides (1.1%). The prevalence among urban children
      were E. coli (26%), A. lumbricoides (21%), B. hominis (18%), G. lamblia (14%), T.
      trichiura (8%), I. butschlii (4%) and A. duodenale (1%). Overall, comparative
      significant differences were noted between rural and urban children for E.
      histolytica (4.2 vs. 14%), G. lamblia (17.9 vs. 14%), A. lumbricoides (1.1 vs.
      21%) and T. trichiura (0 vs. 8%), with the major difference being the much higher
      occurrence of A. lumbricoides and T. trichiura infections in urban children.
      CONCLUSIONS: One of the greatest challenges for healthcare professionals is the
      prevention and treatment of protozoal and helminthic parasitic infections. From
      our study we conclude that the prevalence of different pathogenic species of
      amoeba such as Entamoeba histolytica (4.2 vs. 0%) and G. lamblia (17.9 vs. 14%),
      (P value was equal to 1) was significantly higher among rural children compared
      to children from urban areas. In contrast, the prevalence of nematodes such as A.
      lumbricoides (21% vs. 1.1%), T. trichiura (8% vs. 0%) and A. duodenale (1%) was
      also significantly higher among rural children.

PMID- 20699512
TI  - Phenotypic and molecular characterization of clinically isolated Escherichia
      coli.
AB  - All diarrheagenic Escherichia coli carry at least one virulence-related property.
      Stool samples from 244 patients having acute or persistent diarrhea received
      after the exclusion of routine enteropathogens were investigated. Purely or
      predominantly isolated E. coli (n = 100) were subjected to serotyping, of which
      only 25 were typable. They belonged to 14 different O-serogroups comprising 5
      O153, 4 O102, 3 O25, 2 each of O130 and O169, and 1 each of O1, O8, O15, O37,
      O86, O101, O127, O143, and O160. The typable E. coli isolates along with 5 other
      untypable isolates were investigated for molecular markers, such as intimin
      (eae), enterohemolysin (EhlyA), a-hemolysin, heat-labile enterotoxins (LT), heat
      stable enterotoxins (STa), verotoxins (VT1 and VT2), invasivity (ial),
      enteroaggregative E. coli (EAEC) gene (EAGG), and enterotoxin (EAST). Two of the
      isolates (O153 and O86) were positive for enterohemolysin phenotypically and 5
      for beta-hemolysin both phenotypically and genotypically. Interestingly, 16.6% of
      the randomly isolated E. coli were O153, a serogroup common in cattle, and 10%
      belonged to EAEC pathotype of which two-thirds had the EAST gene, which is quite
      frequent in these strains. Additionally, there was one strain (O153) that was
      positive for EAST only. Between the two 0130:H6 strains isolated, one belonged to
      EAEC serogroup. None of the E. coli isolated were positive for verotoxins, eae,
      LT1, STa, and ial. Data obtained emphasize the need for additional research into
      the role of eae gene and other putative factors affecting the virulence of
      diarrheagenic E. coli in India.

PMID- 20699513
TI  - Novel restriction enzyme SSiI for the detection of mutation in GyrA gene of
      Salmonella enterica serovar Typhi.
AB  - AIM: Enteric fever is an ongoing problem in the developing nations. Resistance
      and reduced susceptibility to ciprofloxacin narrows the therapeutic options in
      enteric fever. The present study was carried out with the objective of
      determining molecular basis of resistance to fluoroquinolone among the clinical
      isolates of Salmonella enterica serovar Typhi from different parts of India.
      MATERIALS AND METHODS: A total of 60 S.Typhi clinical isolates were subjected to
      antimicrobial susceptibility testing and determination of minimum inhibitory
      concentration (MIC) to ciprofloxacin and nalidixic acid. Polymerase chain
      reaction (PCR) for GyrA gene followed by restriction fragment length polymorphism
      (RFLP) with restriction enzyme (RE) SSiI was performed to detect mutation at
      position Ser83. Further confirmation of mutation was done by nucleotide
      sequencing of GyrA gene. RESULTS: Isolates showed 100% sensitivity to first-line
      drugs ampicillin, chloramphenicol, and cotrimoxazole. Twelve of the 60 isolates
      (18%) were susceptible to nalidixic acid (NASST) and the remaining 48 (82%) were
      resistant to nalidixic acid (NARST). Of these 48 NARST strains, 46 (97.5%) had
      reduced susceptibility to ciprofloxacin (MIC 0.25-1.0 microg/mL), whereas 2
      strains (2.75%) were resistant to ciprofloxacin (MIC 4.0 microg/mL). In RFLP
      analysis, all the NASST strains showed 3 fragments, whereas all the NARST strains
      showed 2 fragments due to the loss of 1 restriction site as a result of mutation.
      All the NARST strains with reduced susceptibility to ciprofloxacin (n = 46) had a
      single mutation in gyrA gene (Ser 83-->Tyr or Ser 83-->Phe), whereas double
      mutations (Ser 83-->Phe and Asp 87-->Asn) were found in each of the 2
      ciprofloxacin-resistant strains. None of the NASST strains (n = 12) revealed any
      mutation. CONCLUSION: Our study exemplifies the correlation between nalidixic
      acid screening test, MIC values, and the detection of mutation in GyrA gene by
      PCR-RFLP with a novel RE SSiI.This was further confirmed by nucleotide
      sequencing.

PMID- 20699514
TI  - Comparative study of adherence of oral Candida albicans isolates from HIV sero
      positive individuals and HIV sero-negative individuals to human buccal epithelial
      cells.
AB  - AIM: Candida albicans occurs as a commensal of the gastrointestinal tract. Under
      predisposing conditions, candida can produce a broad array of infections. HIV
      seropositive individuals show increased oral colonization compared to the HIV
      seronegative healthy individuals. C. albicans shows a variety of pathogenic
      factors. We have studied one such factor here; the adherence property of C.
      albicans isolated from HIV seropositive individuals and HIV seronegative to Human
      Buccal Epithelial Cells (HBEC) of normal healthy individuals. MATERIALS AND
      METHODS: Concentrated oral rinse specimen were collected from 50 healthy
      volunteers (control group) and 25 HIV positive individuals (test group) and used
      for isolation of C. albicans. Adherence assay was done using C. albicans isolates
      from both groups on HBEC collected from HIV sero-negative, normal individuals.
      The adherence assay method described by Kimura and Pearsall was used with minor
      modification. STATISTICAL ANALYSIS USED: The results of Adhesion assay were
      subjected to statistical analysis using student "t" test. RESULTS: C. albicans
      isolated from both the groups were tested for their adherence property to normal
      HBEC. The isolates from test group showed more adherence to HBEC compared to
      those of the control group, with average rate of adherence being 56.6%. The
      control group showed average adherence rate of 29.1%. This was statistically
      significant with p value equal to 0.05. CONCLUSION: C. albicans from HIV infected
      individuals showed significant rise in degree of adhesion to the buccal
      epithelial cells than the isolates from healthy controls, suggesting the
      enhancement of virulence factors such as adherence in the presence of
      predisposing condition.

PMID- 20699515
TI  - P16INK4A and MIB-1: an immunohistochemical expression in preneoplasia and
      neoplasia of the cervix.
AB  - AIM: To evaluate the potential of p16INK4A and MIB-1 and to compare the
      expression and interrelationship of these markers in cervical preneoplasias and
      neoplasias. MATERIALS AND METHODS: Immunohistochemical analysis of p16 and MIB-1
      was performed in n = 63 tissue sections and by matching the corresponding
      Papanicolaou smears. Staining intensity for p16 was determined using the 0-3
      grading system. For MIB-1, labelling indices (LI) were calculated and grading was
      performed using the I-III scoring system. RESULTS: No positive staining of p16
      was observed in the normal cervical epithelium. With increasing severity of
      cervical intraepithelial neoplasias (CIN), the p16 expression increased
      progressively. Significant up-regulation of p16 was observed in carcinoma cervix.
      MIB-1 LI was observed to increase with increasing grades of CIN, and significant
      overexpression of MIB-1 was observed in carcinoma cervix. Correlation between
      grades of p16 and that of MIB-1 among cervical neoplasias showed an increasing
      p16 expression with consistently increasing MIB-1 LI in the groups of increasing
      severity. CONCLUSION: This pattern of overexpression of p16 and MIB-1 demonstrate
      their use as a diagnostic marker for cervical neoplastic lesion. Therefore, p16
      and MIB-1 markers in tissue sections can be used as an adjunct to definitively
      diagnose preneoplastic and neoplastic lesions in the cervix.

PMID- 20699516
TI  - Mediastinal liposarcoma of mixed type in childhood: a report of a case with
      unusual histologic features.
AB  - We hereby report the occurrence of mediastinal liposarcoma in a 11-year-old
      female child. Dyspnea and wheezing of long-standing duration were the presenting
      complaints and a preoperative biopsy failed to yield the diagnosis. Histologic
      examination revealed heterogeneous areas with well-differentiated liposarcoma
      like areas, areas resembling myxoid liposarcoma, and areas of dedifferentiation.
      Osteosarcomatous foci and whorled areas reminiscent of meningioma were identified
      in the dedifferentiated areas. Liposarcomas in the mediastinum are extremely rare
      tumors of childhood and the present case showed unusual histologic features.
      Complete surgical excision with clear surgical margins remains the primary
      modality of treatment, although chemotherapy and radiotherapy have been tried.

PMID- 20699517
TI  - Inflammatory myofibroblastic tumor parieto-occipital bone.
AB  - Inflammatory myofibroblastic tumor is a diverse group of lesions first described
      in lung and later on reported in various sites like stomach, bowel, spleen, bone.
      We report a case of inflammatory myofibroblastic tumor in a 30-year-old male who
      presented with a slowly progressive scalp swelling of two-year duration. Magnetic
      resonance imaging showed an intradiploic well enhancing lesion in parietal and
      occipital bone, isointense on T1 weighted images and hypo intense on T2 weighted
      images with dural enhancement. On histopathological examination, the lesion was
      composed of variable admixture of spindle cells with eosinophilic cytoplasm and
      inflammatory cells comprising of plasma cells and lymphocytes. The lesion was
      infiltrating the underlying dura. The spindle cells showed strong positivity for
      smooth muscle actin on immunohistochemistry. A final histopathologic diagnosis of
      inflammatory myofibroblastic tumor was rendered.

PMID- 20699518
TI  - Right atrial appendage thrombus with atrial infarct in a case of thyrotoxicosis:
      an autopsy report.
AB  - Cardiac function has long been known to be altered in patients with
      thyrotoxicosis and atrial fibrillation occurs in patients with hyperthyroidism.
      In addition to its disabling symptoms, atrial fibrillation is a strong risk
      factor for systemic embolism, especially with regard to cerebral circulation. A
      right atrial appendage thrombus formation in atrial fibrillation is a rare
      phenomenon. In this report, we describe a case of a 30-year-old female, who
      suffered from hyperthyroidism and subsequently developed atrial fibrillation and
      a right atrial appendage thrombus with infarction of right atrial appendage.

PMID- 20699519
TI  - Kaposi's sarcoma: HIV-negative man with isolated penile localization.
AB  - Kaposi's sarcoma is the malignant proliferation of the endothelial cell vessels.
      Its genesis is still unclear; however, it seems to be related to the herpes virus
      infection (HHV-8). This neoplasia usually affects the lower limbs and the
      affected persons are mostly from the Mediterranean region. The exclusive penile
      localization of the Kaposi's sarcoma in a patient with a negative HIV serologia
      is exceptional. Our case is of a 73-year old patient with a negative HIV serology
      presenting an exclusive penile localization of the Kaposi's sarcoma treated by
      radiotherapy.

PMID- 20699520
TI  - Solid variant of papillary carcinoma of nipple: an under recognized entity.
AB  - Papillary lesions of the breast represent a heterogeneous group with differing
      biological behavior. Solid papillary carcinomas are uncommon tumors composed of
      circumscribed large cellular nodules separated by bands of fibrosis. Correct
      diagnosis is crucial but may be difficult, as many other benign and malignant
      lesions have similar histological appearances. Immunohistochemistry plays a
      useful role in their differentiation. We describe one such case of a solid
      variant of papillary carcinoma of the left nipple in a 75-year-old woman, who had
      no other palpable mass in rest of the breast tissue. The case is documented for
      the rarity of its occurrence and significance of recognition of this lesion.

PMID- 20699521
TI  - Papillary renal cell carcinoma with lipocyte-like cells: a rare morphological
      variant or an indication of aggressiveness?
AB  - Papillary renal cell carcinoma (PRCC) is the second most common carcinoma of the
      kidney, which is classified into two types. Type 1 displays single layer of cells
      with scanty pale cytoplasm and type 2 has pseudostratified high-grade nuclei with
      eosinophilic cytoplasm. Recently, apart from these two types, oncocytic PRCC and
      clear-cell PRCC have been described. To the best of our knowledge, lipocyte-like
      cells have not yet been reported to accompany any subtypes of renal cell
      carcinoma. Herein, we report a case of PRCC with lipocyte-like cells and
      sarcomatoid features. Lipocyte-like cells might represent a special type of PRCC
      or this feature may be an indication of poor prognosis regarding its association
      with sarcomatoid change.

PMID- 20699522
TI  - A giant solitary fibrous tumor of the pleura: diagnostic implications in an
      unusual case with literature review.
AB  - A solitary fibrous tumor of the pleura (SFTP) is an uncommon tumor, in contrast
      to a relatively common mesothelioma in pleura. Its average size varies from 6 to
      8 cm. We report herein a case of a giant SFTP in a 53-year-old man who presented
      with cough since five years along with chest pain on the left side and
      progressive dyspnea since two months. Radiological findings revealed a large
      pleural mass measuring 25 cm in its largest dimension, filling the pleural cavity
      with effusion. Biopsy showed a spindle cell tumor with areas of dense sclerosis.
      Subsequent excision unraveled a large multinodular, grey-white tumor,
      histologically, composed of spindle cells in a 'patternless' arrangement in dense
      collagenous stroma with areas of hyalinization. Focal areas showed
      hypercellularity with atypia and mitoses, but less than 4/10 High-Power Field,
      unassociated with necrosis. On immunohistochemistry, tumor cells showed diffuse
      positivity with vimentin, CD34 and BCL2 along with cytoplasmic positivity for
      MIC2 (CD99), whereas cytokeratin, EMA, calretinin and HBME-1 were negative.
      Diagnosis of an SFTP was substantiated over a close differential of a
      desmoplastic mesothelioma. In view of atypical features, a close follow-up of the
      case was recommended.

PMID- 20699523
TI  - Squamous cell carcinoma associated with tall cell variant of papillary carcinoma
      of the thyroid.
AB  - We report the simultaneous occurrence of the tall cell variant of papillary
      carcinoma and squamous cell carcinoma in the thyroid gland. Histology and
      immunohistochemical findings are discussed and it seems that the malignant
      squamous component was transformed from the tall cell variant of papillary
      carcinoma. Metastasis from the squamous cell carcinoma is diagnosed in the
      regional lymph node.

PMID- 20699524
TI  - Coexistent lymphoma with tuberculosis and Kaposi's sarcoma with tuberculosis
      occurring in lymph node in patients with AIDS: a report of two cases.
AB  - Although there have been a few reports of simultaneous infections and neoplasm in
      patients with acquired immune deficiency syndrome, no reports of coexistent
      lymphoma with tuberculosis and Kaposi's sarcoma with tuberculosis occurring in
      the same lymph node have been described. In this article, we describe coexistent
      lymphoma with tuberculosis in one case and Kaposi's sarcoma with tuberculosis in
      another case of human immune deficiency virus-infected individuals.

PMID- 20699525
TI  - A fulminant case of acute respiratory distress syndrome associated with
      Mycoplasma pneumoniae infection.
AB  - Acute respiratory distress syndrome (ARDS) caused by mycoplasmas is very rare.
      This report describes a severe case of atypical pneumonia due to M. pneumoniae in
      a formerly healthy young woman who developed high grade fever and cough leading
      to severe disseminated lung disease and finally to fatal ARDS. This case came
      into picture when killer atypical pneumonia, namely, SARS (severe acute
      respiratory syndrome), spread very fast from South-Asian countries to the rest of
      the world. Moreover, the clinical presentation and radiologic features of SARS
      bear resemblance to the syndrome of atypical pneumonia, which lead us to
      investigate this case into detail. We suggest that M. pneumoniae infections
      should be included in the differential diagnosis of pathogens causing ARDS,
      establishing an early diagnosis may have important therapeutic implications.

PMID- 20699526
TI  - Portal duodenopathy presenting as polyposis.

PMID- 20699527
TI  - Glial heterotopia of the scalp.

PMID- 20699528
TI  - Fibrolipoma of the tonsil.

PMID- 20699529
TI  - Entomophthoromycosis of face.

PMID- 20699530
TI  - Onychomycosis due to ascomycete Chaetomium globosum: a case report.

PMID- 20699532
TI  - Comments: Siderophore production by uropathogenic Escherichia coli.

PMID- 20699531
TI  - Chryseomonas luteola bacteremia in a patient with left pyocele testis with
      Fournier's scrotal gangrene.

PMID- 20699533
TI  - Ophthalmic telepathology: Concept and practice.

PMID- 20699534
TI  - Scalp abscess due to Salmonella typhimurium.

PMID- 20699535
TI  - Tumoral pseudoangiomatous stromal hyperplasia of the breast: a rare entity.

PMID- 20699536
TI  - Trauma patient with M-antibody.

PMID- 20699537
TI  - Anti Kp a antibody: a rare alloantibody in a multitransfused thalassemic of
      Indian origin.

PMID- 20699538
TI  - Reactive histiocytosis: a diagnostic dilemma in multiple myeloma.

PMID- 20699539
TI  - Granular cell tumor of gastric mucosa.

PMID- 20699540
TI  - Tuberculosis of the thyroid presenting as multinodular goiter with
      hypothyroidism: a rare presentation.

PMID- 20699541
TI  - Retroperitoneal fetiform teratoma.

PMID- 20699542
TI  - Metastatic synovial sarcoma, masquerading a carcinoma from a tonsillar primary: a
      rare case presentation.

PMID- 20699543
TI  - Corpora amylacea in prostatic stromal smooth muscle cells.

PMID- 20699544
TI  - Inflammatory myofibroblastic tumor of the pancreas: a rare entity.

PMID- 20699545
TI  - Post traumatic fungal keratitis caused by Acremonium recifei.

PMID- 20699546
TI  - An unusual case of primary intrapelvic hydatid cyst.

PMID- 20699548
TI  - Leiomyoma of rectus sheath: an uncommon entity: report of two cases.

PMID- 20699547
TI  - Candida glabrata: etiologic agent of soft tissue abscess in a diabetic patient.

PMID- 20699549
TI  - Extragonadal yolk sac tumor of face in a female infant: a case report.

PMID- 20699550
TI  - Soystatin (VAWWMY), a novel bile acid-binding peptide, decreased micellar
      solubility and inhibited cholesterol absorption in rats.
AB  - This study was designed to identify a novel peptide derived from soybean protein
      that induces inhibition of cholesterol absorption in vivo. VAWWMY (Val-Ala-Trp
      Trp-Met-Tyr, designated soystatin) had a significantly greater ability to bind
      bile acid than soybean protein peptic hydrolysate (SPH) or casein tryptic
      hydrolysate (CTH). Surprisingly, the bile-acid binding ability of VAWWMY was
      almost as strong as that of the hypocholesterolemic medicine cholestyramine. The
      micellar solubility of cholesterol was significantly lower in the presence of
      VAWWMY than in that of SPH or CTH. We found that soystatin derived from soybean
      glycinin acted as an inhibitor of cholesterol absorption in vivo.

PMID- 20699551
TI  - Purification and characterization of termite endogenous beta-1,4-endoglucanases
      produced in Aspergillus oryzae.
AB  - Although termites are known to have a highly efficient lignocellulose-digesting
      system, mass production of native endogenous cellulases of termites has failed in
      Escherchia coli, and in Saccharomyces cerevisiae, and it has not been
      accomplished. Here we report the successful production, purification, and
      characterization of two termite endogenous beta-1,4-endoglucanases, RsEG and
      NtEG, from the salivary gland of Reticulitermes speratus and the midgut of
      Nasutitermes takasagoensis respectively, using Aspergillus oryzae as host. Thin
      layer chromatography analysis showed that both enzymes hydrolyzed the beta-1,4
      cellulosic linkage of cellodextrin into cellobiose and glucose. Kinetic studies
      indicated that the specific activity and Vmax values of the two enzymes were
      significantly higher than those of previously reported fungal and bacterial
      endoglucanases.

PMID- 20699552
TI  - Evaluation of an edible blue-green alga, Aphanothece sacrum, for its inhibitory
      effect on replication of herpes simplex virus type 2 and influenza virus type A.
AB  - A hot-water extract of Aphanothece sacrum, an edible aquacultured blue-green
      alga, was found to show a remarkable inhibitory effect on the replication of
      enveloped viruses including herpes simplex virus type 2 (HSV-2) and influenza
      virus type A (IFV-A, H1N1) in vitro. The main active components were suggested to
      be sulfated polysaccharides in non-dialyzable portion (ASWPH). ASWPH was found to
      inhibit the viral adsorption to the receptor of the host cells involved in the
      replication process of HSV-2 and IFV-A. In addition, while the penetration stage
      of HSV-2 was also significantly suppressed with ASWPH, no such effect was
      observed in the replication of IFV-A. These results suggest that ASWPH might be
      useful in the prevention of infectious diseases caused by HSV-2 as well as IFV-A.

PMID- 20699553
TI  - Practical preparation of epilactose produced with cellobiose 2-epimerase from
      Ruminococcus albus NE1.
AB  - A practical purification method for a non-digestible disaccharide, epilactose (4
      O-beta-galactosyl-D-mannose), was established. Epilactose was synthesized from
      lactose with cellobiose 2-epimerase and purified by the following procedure: (i)
      removal of lactose by crystallization, (ii) hydrolysis of lactose by beta
      galactosidase, (iii) digestion of monosaccharides by yeast, and (iv) column
      chromatography with Na-form cation exchange resin. Epilactose of 91.1% purity was
      recovered at 42.5% yield.

PMID- 20699554
TI  - Artificial food colorants inhibit superoxide production in differentiated HL-60
      cells.
AB  - We tested synthetic food colorants for their antioxidative potential by the in
      vitro superoxide generation assay in differentiated HL-60 cells in response to
      phorbol ester. Among the 12 colorants tested, such fluorescein-type red colorants
      as rose bengal showed potent inhibitory activity without any cytotoxicity under
      dark conditions. The intracellular accumulation and superoxide anion scavenging
      effect of rose bengal were at least partly involved in the inhibitory activity.

PMID- 20699555
TI  - Kaempferol enhanced the intracellular thioredoxin system in normal cultured human
      keratinocytes.
AB  - The effects of kaempferol on redox-associated enzymes in normal human
      keratinocytes were studied. It enhanced the gene expression of thioredoxin
      reductase 1 and thioredoxin. Flavonols had higher ability to induce the
      expression of these genes than the other anti-oxidants and the other flavonoids
      tested. Furthermore, kaempferol and quercetin increased the activity of
      thioredoxin reductase in normal human keratinocytes.

PMID- 20699556
TI  - Effect of neuroprotective flavonoids of Agrimonia eupatoria on glutamate-induced
      oxidative injury to HT22 hippocampal cells.
AB  - A methanolic extract of Agrimonia eupatoria (Rosaceae) significantly attenuated
      glutamate-induced oxidative stress in HT22 hippocampal cells. A new flavonoid,
      characterized as kaempferol 3-O-beta-D-(2''-O-acetyl-6''-(E)-p-coumaroyl)
      glucopyranoside (2''-acetyl-tiliroside (1), was isolated from the methanolic
      extract of A. eupatoria stems together with nine known flavonoids. Compounds 4,
      7, 8 and 9 all showed a neuroprotective effect on glutamate-induced toxicity in
      HT22 cells.

PMID- 20699557
TI  - Extracellular carbohydrate esterase from the basidiomycete Coprinopsis cinerea
      released ferulic and acetic acids from xylan.
AB  - cDNA encoding an extracellular carbohydrate esterase (CcEst1) was cloned from the
      basidiomycete Coprinopsis cinerea. The recombinant CcEst1 expressed in Pichia
      pastoris acted on p-nitrophenyl acetate, alpha-naphthyl acetate, and methyl
      hydroxycinnamic acids, except for methyl sinapic acid. The enzyme released
      ferulic and acetic acids from wheat arabinoxylan and acetylated xylan
      respectively. Activity increased on the addition of endo-beta-1,4-xylanase.

PMID- 20699558
TI  - Production of P(3-hydroxybutyrate-co-3-hydroxyhexanoate-co-3-hydroxyoctanoate)
      terpolymers using a chimeric PHA synthase in recombinant Ralstonia eutropha and
      Pseudomonas putida.
AB  - Recombinant strains of Ralstonia eutropha and Pseudomonas putida harboring a
      chimeric polyhydroxyalkanoate (PHA) synthase, which consisted of PHA synthases of
      Aeromonas caviae and R. eutropha, produced 3-hydroxybutyrate (3HB)-based PHA
      copolymers comprised of 3-hydroxyhexanoate and 3-hydroxyoctanoate units from
      dodecanoate (87-97 mol % 3HB), indicating that the chimeric PHA synthase
      possesses desirable substrate specificity leading to the production of 3HB-rich
      copolymers.

PMID- 20699559
TI  - Isolation and characterization of a novel fucoidan-degrading microorganism.
AB  - A bacterium utilizing fucoidan from the brown alga Cladosiphon okamuranus as sole
      carbon source was isolated and identified as Flavobacterium sp. F-31. The strain
      produced intracellular enzymes involved in fucoidan degradation and desulfation,
      but desulfation activity was not detected until the molecular weight of fucoidan
      fell to less than several tens of thousands due to enzymatic degradation. Only
      fucoidan proved to be an inducible substance for the production of the degrading
      enzymes.

PMID- 20699560
TI  - The peroxisomal catalase gene in the methylotrophic yeast Pichia methanolica.
AB  - In this paper, we describe the CTA1 gene, which encodes a peroxisomal catalase in
      the methylotrophic yeast Pichia methanolica. The P. methanolica CTA1 gene
      (PmCTA1) comprises a 1,530-bp open reading frame corresponding to a protein of
      510 amino acid residues, and its deduced amino acid sequence shows high
      similarity to those of Cta1ps from other methylotrophic yeasts (about 79%).
      Expression of PmCTA1 in a peroxisomal catalase-depleted (Cbcta1Delta) Candida
      boidinii strain restored the methylotrophic growth of the host strain, while the
      expression of PmCTA1-DeltaSRL, which lacks peroxisome targeting signal type 1,
      did not. In P. methanolica, expression of PmCTA1 was induced when cells were
      grown on peroxisome-inducing carbon sources, viz., methanol, oleate, and D
      alanine. Taken together, these results indicate that PmCTA1 encodes a functional
      peroxisomal catalase in P. methanolica.

PMID- 20699561
TI  - The synergy of 6-O-sulfation and N- or 3-O-sulfation of chitosan is required for
      efficient inhibition of P-selectin-mediated human melanoma A375 cell adhesion.
AB  - We prepared chitosan sulfated derivatives to address the common structural
      requirement of the sulfate pattern to block P-selectin-mediated tumor cell
      adhesion. Our results indicate that 6-O-sulfation of chitosan is indispensable
      for inhibition of P-selectin binding to human melanoma A375 cells. Furthermore,
      additional N-sulfation or 3-O-sulfation dramatically enhanced the inhibitory
      activity of 6-O-sulfated chitosan, suggesting that efficient anti-P-selectin
      adhesion activity of sulfated saccharides requires the synergy of 6-O-sulation
      and N- or 3-O-sulfation in glucosamine units.

PMID- 20699562
TI  - The occurrence of renin inhibitor in rice: isolation, identification, and
      structure-function relationship.
AB  - We found renin inhibitory activity in rice. The physico-chemical data on the
      isolated inhibitors were identical to those of oleic acid and linoleic acid.
      Oleic acid and linoleic acid competitively inhibited renin activity, with K(i)
      values of 15.8 and 19.8 microM respectively. Other unsaturated free fatty acids
      also inhibited renin activity, but saturated fatty acids had no effect on it.

PMID- 20699563
TI  - Cloning and characterization of a Lentinula edodes class II chitin synthase gene,
      LeChs2.
AB  - A genomic DNA sequence and cDNA encoding a putative chitin synthase were isolated
      from the white rot basidiomycete Lentinula edodes. The gene, named LeChs2,
      consists of a 2,598-bp open reading frame interrupted by 14 introns and encodes a
      putative protein of 866 amino acid residues. The data obtained in this study
      suggest that LeChs2 belongs to the class II chitin synthases.

PMID- 20699564
TI  - A new beneficial mutation in pseudomonas sp. 61-3 polyhydroxyalkanoate (PHA)
      synthase for enhanced cellular content of 3-hydroxybutyrate-based PHA explored
      using its enzyme homolog as a mutation template.
AB  - A newly isolated mutation (Gln508Leu) and a combination of it with previously
      discovered beneficial mutations in polyhydroxyalkanoate synthase 1 from
      Pseudomonas sp. 61-3 were found to enhance the production of poly(3
      hydroxybutyrate) [P(3HB)] and poly(3HB-co-3-hydroxyalkanoate)s in recombinant
      Escherichia coli.

PMID- 20699565
TI  - Galangal pungent component, 1'-acetoxychavicol acetate, activates TRPA1.
AB  - We investigated the activation of transient receptor potential cation channel
      (TRP) subfamily V, member 1 (TRPV1) and TRP subfamily A, member 1 (TRPA1) by 1'
      acetoxychavicol acetate (ACA), the main pungent component in galangal. ACA did
      not activate TRPV1-expressing human embryonic kidney (HEK) cells, but strongly
      activated TRPA1-expressing HEK cells. ACA was more potent than allyl
      isothiocyanate, the typical TRPA1 agonist.

PMID- 20699566
TI  - High-fat diet lowers the nutritional status indicators of pantothenic acid in
      weaning rats.
AB  - Weaning rats were fed a 5% or 30% fat diet containing limited calcium
      pantothenate for 28 d. The plasma, liver and adrenal pantothenic acid levels in
      the rats fed on the 30% fat diet were significantly lower than with the 5% fat
      diet. The results suggest that the high-fat diet affected pantothenic acid
      metabolism.

PMID- 20699567
TI  - Vacuolar amino acid transporter Avt5p is responsible for lithium uptake in
      Schizosaccharomyces pombe.
AB  - The fission yeast Schizosaccharomyces pombe was sensitive to salinity; cell
      growth was stopped by 0.5 M NaCl and by 10 mM LiCl. The avt5+ gene encodes a
      vacuolar transporter with a broad specificity for amino acids. We found that the
      avt5Delta mutant became highly tolerant of Li+ and Na+ in growth. Concanamycin A
      sensitive Li+ uptake as well as cellular Li+ content was lower in the avt5
      mutant, suggesting a role of Avt5p in cellular uptake of toxic Li+.

PMID- 20699568
TI  - A role of the cspA gene encoding a mycolyltransferase in the growth under
      alkaline conditions of Corynebacterium glutamicum.
AB  - Corynebacterium glutamicum is widely used in the industrial production of amino
      acids. Producer strains are generated by classical random mutagenesis, and
      therefore have detrimental characteristics caused by unnecessary mutations.
      Increased alkali sensitivity is one of those undesired characteristics. We found
      that one of the laboratory strains, AJ12036DeltacspADeltacspB, showed decreased
      growth under alkaline conditions. To clarify which mutation is responsible for
      alkali sensitivity, we constructed mutant strains carrying the DeltacspA and/or
      DeltacspB mutations from wild-type strain ATCC13869. We found that disruption of
      cspA encoding a mycolyltransferase alone caused increased alkali sensitivity. The
      DeltacspA mutant also showed increased susceptibility to ethambutol, penicillin,
      and rifampicin. Disruption of cspB had no effect on alkali sensitivity or drug
      sensitivity. These results indicate that the mycolate layer is important for
      alkali sensitivity as well as drug susceptibility in this bacterium.

PMID- 20699569
TI  - Mitogenic activity of CEL-I, an N-acetylgalactosamine (GalNAc)-specific C-type
      lectin, isolated from the marine invertebrate Cucumaria echinata (Holothuroidea).
AB  - An N-acetylgalactosamine (GalNAc)-specific Ca(2+)-dependent lectin (C-type
      lectin), isolated from the marine invertebrate Holothuroidea (Cucumaria
      echinata), CEL-I, showed potent mitogenic activity toward normal mouse spleen
      cells. The mitogenic activity of CEL-I, which reached a maximum at 100 microg/ml,
      was inhibited by GalNAc in a concentration-dependent manner. The mitogenic effect
      of CEL-I at 10 microg/ml on T cell- enriched splenocytes was at a similar level
      due to a well-known T cell mitogen, concanavalin A (Con A), at 10 microg/ml.
      Furthermore, CEL-I evoked a mitogenic response from nude mouse spleen cells,
      while no significant effects of Con A on this cell population were observed over
      a wide range of concentrations. These results suggest that CEL-I is a potent
      mitogenic lectin with the ability to stimulate both T and B cells.

PMID- 20699570
TI  - Thermal denaturation profiles of tuna myoglobin.
AB  - Myoglobin (Mb) purified from fast skeletal muscle of bluefin tuna Thunnus thynnus
      orientalis was subjected to thermal treatment, and the denaturation profiles were
      examined by thermodynamic analysis. Based on the ellipticity or helical content
      obtained by circular dichroism (CD) spectrometry, it was found that denaturation
      of tuna Mb consisted of three steps, and that slight structural changes of Mb
      started below 20 degrees C. However, major structural changes were observed at
      around 58 and 72 degrees C. Differential scanning calorimetry (DSC) analysis
      revealed a similar but somewhat different thermal denaturation profile of Mb. In
      comparison with the denaturing profiles of whale Mb under the same conditions,
      the thermal stability of tuna Mb was found to be much lower. In the modeled
      tertiary structures of these Mbs, they were roughly similar to each other, though
      minor conformational differences were recognized and the total energy was found
      to be lower for tuna Mb.

PMID- 20699571
TI  - Vestitol as a chemical barrier against intrusion of parasitic plant Striga
      hermonthica into Lotus japonicus roots.
AB  - The root parasitic plant, Striga hermonthica, constrains the production of
      several agronomically important poaceous crops in the arid and semiarid tropical
      regions of Sub-Saharan Africa. The parasite is incompatible with the model
      legume, Lotus japonicus. Studies at the molecular and metabolic levels have
      revealed that expression of the genes involved in the biosynthesis of vestitol, a
      legume-specific phytoalexin, was highly up-regulated in L. japonicus roots
      challenged with S. hermonthica. High-performance liquid chromatography and mass
      spectroscopy confirmed the presence of vestitol in the exudate released from L.
      japonicus roots inoculated with S. hermonthica seedlings. Fluorescence, similar
      to that emitted by authentic vestitol, was displayed on the surface of L.
      japonicus roots to which successful attachment of S. hermonthica had been
      achieved. Vestitol exerted a limited inhibitory effect on S. hermonthica
      germination, but it significantly inhibited seedling growth. These results
      indicate that vestitol biosynthesis in L. japonicus was induced by S. hermonthica
      attachment and that vestitol contributed, at least in part, to the host's defence
      mechanism and acted as a chemical barrier against the intrusion of the parasite.

PMID- 20699572
TI  - Purification and characterization of membrane-associated hydrogenase from the
      deep-sea epsilonproteobacterium Hydrogenimonas thermophila.
AB  - Membrane-associated hydrogenase was purified from the chemolithoautotrophic
      epsilonproteobacterium Hydrogenimonas thermophila at 152-fold purity. The
      hydrogenase was found to be localized in the periplasmic space, and was easily
      solubilized with 0.1% Triton X-100 treatment. Hydrogen oxidation activity was
      1,365 micromol H(2)/min/mg of protein at 80 degrees C at pH 9.0, with phenazine
      methosulphate as the electron acceptor. Hydrogen production activity was 900
      micromol H(2)/min/mg of protein at 80 degrees C and pH 6.0, with reduced methyl
      viologen as the electron donor. The hydrogenase from this organism showed higher
      oxygen tolerance than those from other microorganisms showing hydrogen oxidation
      activity. The structural genes of this hydrogenase, which contains N-terminal
      amino acid sequences from both small and large subunits of purified hydrogenase,
      were successfully elucidated. The hydrogenase from H. thermophila was found to be
      phylogenetically related with H(2) uptake hydrogenases from pathogenic
      Epsilonproteobacteria.

PMID- 20699573
TI  - Soybean basic 7S globulin: subunit heterogeneity and molecular evolution.
AB  - Basic 7S globulin, a cysteine-rich protein from soybean seeds, consists of
      subunits containing 27 kD and 16 kD chains linked by disulfide bonding. Three
      differently sized subunits of the basic 7S globulin were detected and partially
      separated by SP Sepharose chromatography. The basic 7S globulin was characterized
      as a member of a superfamily of structurally related but functionally distinct
      proteins descended from a specific group of plant aspartic proteinases.

PMID- 20699574
TI  - Enzymatic-HPLC method to analyze D-3-hydroxybutyric acid in rat serum.
AB  - An enzymatic-HPLC method to analyze the serum concentration of D-3-hydroxybutyric
      acid was developed. A deproteinized sample of rat serum was treated with 3
      hydroxybutyrate dehydrogenase in the presence of NAD, and was analyzed by
      reversed-phase HPLC to separate and quantify NADH formed by the enzyme reaction,
      monitoring OD at 340 nm. Standard samples containing varying amounts of D-3
      hydroxybutyric acid (0-10 nmol in 50 microl) were treated with 3-hydroxybutyrate
      dehydrogenase and analyzed by HPLC (the injected amount was 0-2.7 nmol of D-3
      hydroxybutuyric acid), resulting in the peak area increasing proportionally with
      the injected amount. The method proved sensitive enough for as little as 0.2-2
      nmol D-3-hydroxybutyric acid in 50 microl to be accurately analyzed. Only 10-20
      microl of the rat serum protein-free extract is therefore required to obtain a
      reliable value. The values obtained with this method are identical to those
      observed by the conventional enzyme-spectrophotometric method. This method can be
      easily conducted in many laboratories because it is highly sensitive and only
      requires HPLC apparatus equipped with a UV meter.

PMID- 20699575
TI  - Characterization of starch granules in rice culms for application of rice straw
      as a feedstock for saccharification.
AB  - Rice plants are known to accumulate starch in leaf sheaths and culms, and in some
      cultivars significant amounts of starch are present at the mature stage. This can
      be considered as potential feedstock for the recovery of fermentable sugars. We
      isolated starches from the culms of cultivars Yumeaoba, Koshihikari, and Leafstar
      to investigate their structural and physical features. Yumeaoba culm starch
      contained 20.2% amylose, whereas Koshihikari and Leafstar contained 25.8% and
      25.2%. Yumeaoba culm starch was found by chain-length distribution analysis to
      contain higher amounts of short chains, resulting in lower gelatinization
      temperature by 7 degrees C, as compared to Koshihikari and Leafstar.
      Consequently, the rate of enzymatic hydrolysis of Yumeaoba culm starches reached
      maximum at a lower temperature than Leafstar. Rice culm starch, with a lower
      gelatinization temperature, can provide an advantageous material for feedstock
      for bioethanol production in terms of energy conservation.

PMID- 20699576
TI  - Improved syntheses of morinol C and D by employing Mizoroki-Heck reaction and
      their cytotoxic and antimicrobial activities.
AB  - Improved syntheses of optically pure (-)- and (+)-morinol C, and (-)- and (+)
      morinol D were achieved by employing the Mizoroki-Heck reaction to construct the
      cinnamyl moiety. The protective group of the alkene substrate affected the yield
      of this key reaction. The reaction with a combination of the acetate-protected
      olefin and 4-methoxyphenylboronic acid gave the best result producing morinol C
      and D. All stereoisomers of morinol C and D showed cytotoxic activity, with (R,R)
      morinol C showing the highest antibacterial activity.

PMID- 20699577
TI  - Elevated O-linked N-acetylglucosamine correlated with reduced Sp1 cooperative DNA
      binding with its collaborating factors in vivo.
AB  - O-Linked N-acetylglucosamine (O-GlcNAc), a single GlcNAc modification of
      proteins, is abundant in nucleocytoplasmic proteins of eukaryotes. Most nuclear
      transcriptional regulator proteins carry O-GlcNAc, implicating O-GlcNAc in gene
      regulation. This study suggested the possibility that O-GlcNAc regulates
      cooperative binding of Sp1 and its collaborating transcription factors, Oct1 and
      Elf-1, onto DNA templates in vivo. Chromatin immunoprecipitation assays on cells
      in which O-GlcNAc was modulated pharmacologically revealed that Sp1-Oct1- and Sp1
      Elf-1-paired occupancies of previously known target promoter regions were
      suppressed by elevated O-GlcNAc modification. Since these pairs of transcription
      factors bind the target promoters cooperatively and DNA binding of Sp1 alone is
      not affected by O-GlcNAc, our results imply that O-GlcNAc weakens the DNA binding
      of Sp1 and its cooperative binding partners by inhibiting stable interaction on
      DNA templates.

PMID- 20699578
TI  - Relationship between the rheological properties of thickener solutions and their
      velocity through the pharynx as measured by the ultrasonic pulse Doppler method.
AB  - The dependence of the dynamic viscoelastic parameters of carboxymethylcellulose
      (CMC), xanthan gum, and guar gum solutions on the angular frequency (omega) was
      compared with that of their viscosity (mu) on the shear rate (gamma). In
      addition, the effect of these rheological properties on the maximum velocity
      through the pharynx, V(max), as measured by the ultrasonic pulse Doppler method,
      was investigated. The CMC and guar gum solutions examined were taken as a dilute
      solution and a true polymer solution, respectively. The xanthan gum solution was
      taken as a weak gel above 0.5% and a true polymer solution below 0.2%. The
      maximum velocity, V(max), of the thickener solutions correlated well with mu, the
      dynamic viscosity eta', and the complex viscosity eta(*), especially those
      measured at gamma or omega of 20-30 s(-1) (or rad/s) and above, suggesting that
      mu, eta', and eta(*) are suitable indexes for care foods of the liquid type for
      dysphagic patients.

PMID- 20699579
TI  - Cloning and functional analysis of geraniol 10-hydroxylase, a cytochrome P450
      from Swertia mussotii Franch.
AB  - Swertia mussotii Franch has anti-hepatitis activity and contains a high level of
      iridoid monoterpenoids. The cytochrome P450 monooxygenase (CYP) geraniol 10
      hydroxylase (G10H) is thought to play an important role in iridoid monoterpenoid
      and indole alkaloid biosynthesis. Here we report the isolation of a full-length
      cDNA clone of S. mussotii G10H (SmG10H). The predicted gene product was a 496
      residue protein designated CYP76B10, the sequence of which was highly similar to
      that of the CYP76 family, particularly to Catharanthus roseus G10H (80.2%
      homology). SmG10H transcripts were much more abundant in the leaves than in
      either the root or the stem, and were derived from a single copy gene. SmG10H
      expression was upregulated by treatment with methyljasmonate (MeJA) over a period
      from 6 h to 36 h after treatment. Accumulation of swertiamarin increased after
      elicitation by MeJA. SmG10H was heterologously expressed in both Escherichia coli
      and Pichia pastoris (yeast), forming a 55.5-kDa protein. Based on analysis in
      vitro, SmG10H was found to have catalytic activity hydroxylating geraniol. In the
      SmG10H overexpression plants, the level of SmG10H transcript and the contents of
      10-hydroxygeraniol and swertiamarin increased simultaneously.

PMID- 20699580
TI  - Hypotriacylglycerolemic and antiobesity properties of a new fermented tea product
      obtained by tea-rolling processing of third-crop green tea (Camellia sinensis)
      leaves and loquat (Eriobotrya japonica) leaves.
AB  - We manufactured a new fermented tea by tea-rolling processing of third-crop green
      tea (Camellia sinensis) leaves and loquat (Eriobotrya japonica) leaves. The mixed
      fermented tea extract inhibited pancreatic lipase activity in vitro, and
      effectively suppressed postprandial hypertriacylglycerolemia in rats. Rats fed a
      diet containing 1% freeze-dried fermented tea extract for 4 weeks had a
      significantly lower liver triacylglycerol concentration and white adipose tissue
      weight than those fed the control diet lacking fermented tea extract. The
      activity of fatty acid synthase in hepatic cytosol markedly decreased in the
      fermented tea extract group as compared to the control group. The serum and liver
      triacylglycerol- and body fat-lowering effects of the mixed fermented tea extract
      were strong relative to the level of dietary supplementation. These results
      suggest that the new fermented tea product exhibited hypotriacylglycerolemic and
      antiobesity properties through suppression of both liver fatty acid synthesis and
      postprandial hypertriacylglycerolemia by inhibition of pancreatic lipase.

PMID- 20699581
TI  - Antiobesity effects of Bifidobacterium breve strain B-3 supplementation in a
      mouse model with high-fat diet-induced obesity.
AB  - The aim of the present study was to evaluate the anti-obesity activity of a
      probiotic bifidobacterial strain in a mouse model with obesity induced by a high
      fat diet. The mice were fed a high-fat diet supplemented with Bifidobacterium
      breve B-3 at 10(8) or 10(9) CFU/d for 8 weeks. B. breve B-3 supplementation dose
      dependently suppressed the accumulation of body weight and epididymal fat, and
      improved the serum levels of total cholesterol, fasting glucose and insulin. The
      bifidobacterial counts in the caecal contents and feces were significantly
      increased with the B. breve B-3 administration. The expression of genes related
      to fat metabolism and insulin sensitivity in the gut and epididymal fat tissue
      was up-regulated by this administration. These results suggest that the use of B.
      breve B-3 would be effective in reducing the risk of obesity.

PMID- 20699582
TI  - Practical preparation of D-galactosyl-beta1-->4-L-rhamnose employing the combined
      action of phosphorylases.
AB  - D-Galactosyl-beta1-->4-L-rhamnose (GalRha) was produced enzymatically from 1.1 M
      sucrose and 1.0 M L-rhamnose by the concomitant actions of four enzymes (sucrose
      phosphorylase, UDP-glucose-hexose 1-phosphate uridylyltransferase, UDP-glucose 4
      epimerase, and D-galactosyl-beta1-->4-L-rhamnose phosphorylase) in the presence
      of 1.0 mM UDP-glucose and 30 mM inorganic phosphate. The accumulation of GalRha
      in 1 liter of the reaction mixture reached 230 g (the reaction yield was 71% from
      L-rhamnose). Sucrose and fructose in the reaction mixture were removed by yeast
      treatment, but isolation of GalRha by crystallization after yeast treatment was
      unsuccessful. Finally, 49 g of GalRha was isolated from part of the reaction
      mixture with yeast treatment by gel-filtration chromatography.

PMID- 20699583
TI  - Acetic acid fermentation of acetobacter pasteurianus: relationship between acetic
      acid resistance and pellicle polysaccharide formation.
AB  - Acetobacter pasteurianus strains IFO3283, SKU1108, and MSU10 were grown under
      acetic acid fermentation conditions, and their growth behavior was examined
      together with their capacity for acetic acid resistance and pellicle formation.
      In the fermentation process, the cells became aggregated and covered by amorphous
      materials in the late-log and stationary phases, but dispersed again in the
      second growth phase (due to overoxidation). The morphological change in the cells
      was accompanied by changes in sugar contents, which might be related to pellicle
      polysaccharide formation. To determine the relationship between pellicle
      formation and acetic acid resistance, a pellicle-forming R strain and a non
      forming S strain were isolated, and their fermentation ability and acetic acid
      diffusion activity were compared. The results suggest that pellicle formation is
      directly related to acetic acid resistance ability, and thus is important to
      acetic acid fermentation in these A. pasteurianus strains.

PMID- 20699584
TI  - Synthesis of pseudodeflectusin and ustusorane C: structural revision of
      aspergione a and B.
AB  - The syntheses of racemic and optically active pseudodeflectusin and ustusorane C
      are described. The (1)H- and (13)C-NMR data for our synthetic pseudodeflectusin
      and ustusorane C were identical to those of the corresponding natural products.
      We also synthesized the proposed structure of aspergione A and B whose (1)H- and
      (13)C-NMR data were identical to those of ustusorane C and pseudodeflectusin. The
      (1)H- and (13)C-NMR spectra of our synthetic aspergione A and B were different
      from those of the natural compounds. Our results confirm that aspergione A and B
      are in fact ustusorane C and pseudodeflectusin, respectively.

PMID- 20699585
TI  - Effect of sesame lignans on TNF-alpha-induced expression of adhesion molecules in
      endothelial cells.
AB  - The expression of cell adhesion molecules (CAMs) has been implicated as one of
      the most important causes of the development of inflammatory diseases such as
      atherosclerosis, and, it is speculated that the prevention of it is an effective
      approach to the control of atherosclerosis. In the present study, we investigated
      the effect of sesame lignans on the expression of CAMs in human umbilical vein
      endothelial cells (HUVECs) induced by tumor necrosis factor-alpha (TNF-alpha).
      Based on cell-ELISA analysis, we found that sesaminol-6-catechol downregulated
      the TNF-alpha-induced expression of CAMs in a dose-dependent manner. Moreover,
      these inhibitory effects were caused to be drastically exerted by downregulating
      the CAM proteins in TNF-alpha-activated HUVECs at transcriptional level. This
      suggests, that sesaminol-6-catehcol suppresses the expression of CAMs, and may be
      an active component of sesame lignans.

PMID- 20699586
TI  - Effects of depletion of RNA-binding protein Tex on the expression of toxin genes
      in Clostridium perfringens.
AB  - Tex was originally identified in Bordetella pertussis, where it serves as a
      transcriptional regulator of toxin genes. However, the Tex of Streptococcus
      pneumoniae has no regulatory function in the expression of the pneumococcal major
      toxin pneumolysin. Here, we identified the CPE2168 gene as Tex in Clostridium
      perfringens, and examined the roles of Tex in toxin gene expression. We found
      that the deletion mutant for Tex does not affect growth, but the mRNA levels of
      three hyaluronidase genes (nagH, nagJ, and nagL) and an exo-sialidase (nanJ) were
      reduced to less than 50% as compared to the parent strain, C. perfringens strain
      13. On the other hand, Tex did not affect the expression of proteases,
      enterotoxins, hemolysins, either of two hyaluronidase genes (nagI and nagK), an
      exo-sialidase (nanI), or adhesins. Moreover, purified Tex bound to the 5'-portion
      of target gene mRNAs. Based on these results, we propose that Tex positively
      regulates the gene expression of a set of toxin genes in C. perfringens.

PMID- 20699587
TI  - Antioxidant and antimelanogenic properties of chestnut flower extract.
AB  - In this study, we analyzed the antioxidant and antimelanogenic properties of a
      variety of solvent extracts of pre-bloom and full-bloom chestnut flowers. Among
      the solvent extracts, a pre-bloom methanol extract (preM) and an ethanol extract
      (preE) showed the highest amounts of phenolics (467.92+/-0.45 and 456.24+/-5.88
      mg of gallic acid equivalent/g of extract) and flavonoids (60.96+/-1.86 and
      41.59+/-8.57 mg of quercetin equivalent/g of extract). These extracts exhibited
      the highest DPPH radical and reducing activities, as well as the greatest
      mushroom tyrosinase inhibition activity. In addition, preE effectively protected
      the skin against ultraviolet (UV) rays. Further, extracts were tested for
      cytotoxicity on human melanoma cells (SK-MEL-2), and we observed that all the
      extracts were non-cytotoxic for the cells. Their effects on tyrosinase and
      melanin inhibitory action were further assessed, and we found that all the
      extracts reduced the tyrosinase activity and melanin formation of SK-MEL-2 cells
      as effectively as arbutin. Moreover, the protein level expression of tyrosinase
      decreased dramatically. However, the protein levels of the other melanogenic
      enzymes, tyrosinase-related protein 1 (TRP1) and dopachrome tautomerase (DCT),
      were not altered significantly. Therefore, the antimelanogenic effects of
      chestnut flower extracts were attributable to their inhibitory effects on
      tyrosinase via their anti-oxidative action, making them a strong candidate for
      use in food, cosmetics, and pharmaceutical applications.

PMID- 20699588
TI  - Structural properties of silkworm small heat-shock proteins: sHSP19.9 and
      sHSP20.8.
AB  - sHSP20.8 and sHSP19.9 are silkworm small-heat shock proteins (sHSPs) comprising a
      number of polypeptides of molecular sizes of several tens of kilodaltons as
      subunits. The structural properties of sHSPs were investigated. sHSP19.9 was
      found to be aggregated by itself during incubation at 60 degrees C. Aggregation
      was suppressed in the presence of dithiothreitol and at high ionic strength. In
      contrast, sHSP20.8 was not aggregated. Aggregation of sHSP19.9 was partially
      suppressed by sHSP20.8 and in the presence of catalase as a target protein. Based
      on changes in small-angle X-ray scattering, it is possible that the molecular
      size of sHSP19.9 is larger than that of sHSP20.8, and that their molecular sizes
      increase with increasing temperature in a reversible, biphasic manner. sHSPs did
      not protect catalase from thermal inactivation, but protected it from
      precipitation by forming a soluble complex. sHSP20.8 and sHSP19.9 with
      dithiothreitol were stable against lyophilization, autoclaving at 120 degrees C,
      and boiling.

PMID- 20699589
TI  - Simple purification of a foreign protein using polyhedrin fusion in a baculovirus
      expression system.
AB  - Previously, we found that expression by translational fusion of the polyhedrin
      (Polh)-green fluorescence protein (GFP) led to the formation of granular
      structures, and that these fluorescent granules were easily precipitated by high
      speed centrifugation. Here, we developed an easy, fast, mass purification system
      using this baculovirus expression system (BES). An enhanced GFP (EGFP) fused with
      the Polh gene at the N-terminus, including a linker and enterokinase (EK) site
      between Polh and EGFP, was expressed in Sf9 cells. The cells infected by
      AcPolhEKA-EGFP produced fluorescent granules. The EGFP fusion protein was
      purified from granule-containing cells in three steps: cell harvest, sonication,
      and EK digestion. Through final enterokinase digestion, EGFP presented mainly in
      the supernatant, and this supernatant fraction also showed a pure EGFP band.
      These results suggest that a combined procedure of Polh fusion expression and
      enterokinase digestion can be used for rapid and easy purification of other
      proteins.

PMID- 20699590
TI  - New L-amino acid ligases catalyzing oligopeptide synthesis from various
      microorganisms.
AB  - L-Amino acid ligase synthesizes various peptides from unprotected L-amino acids
      in an ATP-dependent manner. Known L-amino acid ligases catalyze only dipeptide
      synthesis, but recently we found that RizB of Bacillus subtilis NBRC 3134
      catalyzes oligopeptide synthesis. In the present study, we searched for new
      members of the L-amino acid ligase group that catalyze oligopeptide synthesis.
      Several hypothetical proteins possessing the ATP-grasp motif were selected by in
      silico analysis. These recombinant proteins were assayed for L-amino acid ligase
      activity. We obtained five L-amino acid ligases showing oligopeptide synthesis
      activities. These proteins showed low similarity in amino acid sequence, but
      commonly used branched-chain amino acids, such as RizB, as substrates.
      Furthermore, the spr0969 protein of Streptococcus pneumoniae synthesized longer
      peptides than those synthesized by RizB, and the BAD_1200 protein of
      Bifidobacterium adolescentis showed higher activity toward aromatic amino acids
      than toward branched-chain ones. We also examined some of their characteristics.

PMID- 20699591
TI  - Adiposity suppression effect in mice due to black pepper and its main pungent
      component, piperine.
AB  - We investigated energy metabolism enhancement by pepper by examining suppression
      of body fat accumulation in mice due to piperine (PIP) and black pepper (BP)
      intake. To induce adiposity, mice were fed a high-fat, high-sucrose (HFS) diet as
      a control diet for 4 weeks. Visceral fat weights decreased significantly in the
      mice fed diets of 0.03% and of 0.05% PIP. Body weight in the 0.05% PIP group also
      decreased significantly. In the mice fed a diet of 1.0% BP, body weight and
      visceral fat weights decreased significantly. For all parameters tested, the 1.0%
      BP group tended to show values slightly lower than those of the 0.03% PIP group.
      Expression of thermogenic protein uncoupling protein 1 tended to increase in the
      mice on the 1.0% BP diet. These results indicate that BP suppresses the effect of
      body fat accumulation mainly through the action of PIP.

PMID- 20699592
TI  - Agarwood induced laxative effects via acetylcholine receptors on loperamide
      induced constipation in mice.
AB  - Agarwood (Aquilaria sinensis, Aquilaria crasna) is well known as an incense in
      the oriental region such as Thailand, Taiwan, and Cambodia, and is used as a
      digestive in traditional medicine. We investigated the laxative effects and
      mechanism of agarwood leaves extracted with ethanol (EEA-1, Aquilaria sinensis;
      EEA-2, Aquilaria crasna). EEA-1, EEA-2, the main constituents of EEAs
      (mangiferin, and genkwanin-5-O-primeveroside), and senna increased the frequency
      and weight of stools in loperamide-induced constipation model mice. EEA-1 and EEA
      2 did not induce diarrhea as a side effect, but senna induced severe diarrhea.
      EEA-1 and senna increased gastro-intestinal (GI) transit in the model mice. EEA
      1, but not senna, also increased the intestinal tension of isolated jejunum and
      ileum in guinea pigs, and the tension increase was blocked by atropine, a
      muscarinic receptor antagonist, but not by other inhibitors (granicetron,
      pyrilamine, or bradykinin-antagonist peptide). Furthermore, the increase in
      frequency and weight of stools induced by EEA-1 were blocked by pre
      administration of atropine in the model mice. These findings indicate that EEAs
      exerted a laxative effect via acetylcholine receptors in the mouse constipation
      model.

PMID- 20699593
TI  - Consumption of sericin reduces serum lipids, ameliorates glucose tolerance and
      elevates serum adiponectin in rats fed a high-fat diet.
AB  - The effect was examined of dietary sericin on the lipid and carbohydrate
      metabolism in rats fed with a high-fat diet. The rats were fed with a 20% beef
      tallow diet with or without sericin at the level of 4% for 5 weeks. The final
      body weight and white adipose tissue weight were unaffected by dietary
      manipulation. The consumption of sericin significantly reduced the serum levels
      of triglyceride, cholesterol, phospholipids and free fatty acids. Serum very-low
      density lipoprotein (VLDL)-triglyceride, VLDL-cholesterol, low-density
      lipoprotein (LDL)-cholesterol and LDL-phospholipids were also significantly
      reduced by the sericin intake. Liver triglyceride and the activities of glucose 6
      phosphate dehydrogenase and malic enzyme, the lipogenic enzymes, were also
      reduced by the sericin intake. Dietary sericin caused a marked elevation in serum
      adiponectin. The consumption of sericin suppressed the increases in plasma
      glucose and insulin levels after an intraperitoneal glucose injection. These
      results imply the usefulness of sericin for improving the lipid and carbohydrate
      metabolism in rats fed on a high-fat diet.

PMID- 20699594
TI  - Composted oyster shell as lime fertilizer is more effective than fresh oyster
      shell.
AB  - Physio-chemical changes in oyster shell were examined, and fresh and composted
      oyster shell meals were compared as lime fertilizers in soybean cultivation.
      Structural changes in oyster shell were observed by AFM and FE-SEM. We found that
      grains of the oyster shell surface became smoother and smaller over time. FT-IR
      analysis indicated the degradation of a chitin-like compound of oyster shell. In
      chemical analysis, pH (12.3+/-0.24), electrical conductivity (4.1+/-0.24 dS m(
      1)), and alkaline powder (53.3+/-1.12%) were highest in commercial lime. Besides,
      pH was higher in composted oyster shell meal (9.9+/-0.53) than in fresh oyster
      shell meal (8.4+/-0.32). The highest organic matter (1.1+/-0.08%), NaCl (0.54+/
      0.03%), and moisture (15.1+/-1.95%) contents were found in fresh oyster shell
      meal. A significant higher yield of soybean (1.33 t ha(-1)) was obtained by
      applying composted oyster shell meal (a 21% higher yield than with fresh oyster
      shell meal). Thus composting of oyster shell increases the utility of oyster
      shell as a liming material for crop cultivation.

PMID- 20699596
TI  - Association between serum uric acid levels and cardiometabolic risk factors among
      Japanese junior high school students.

PMID- 20699597
TI  - STELLIUM 1: First-in-man follow-up evaluation of bioabsorbable polymer-coated
      paclitaxel-eluting stent.
AB  - BACKGROUND: Durable polymers used for first-generation drug-eluting stents (DES)
      potentially contribute to persistent inflammation and late DES thrombosis. The
      vascular response to the Stellium stent, which is coated with an absorbable
      polymer for slow release of low-dose paclitaxel, was evaluated in the present
      study. METHODS AND RESULTS: The 37 patients with stable angina were implanted
      with 47 Stellium stents. Quantitative coronary angiography (QCA) was performed at
      baseline, and QCA and optical coherence tomography (OCT) were performed at 6
      months post-implant. The primary endpoint was major adverse cardiac events
      (MACE). At 6 months, 1 case of MACE occurred because of total occlusion of a
      protected left main artery. In-stent and segment binary restenosis rates were
      both 0%. In-stent late loss was 0.19 +/- 0.54 mm. Altogether, 5,564 struts were
      visualized by OCT and mean neointimal thickness was 150.03 +/- 146.36 um. The
      number of well-apposed struts with and without neointima overlay was 5,135
      (92.29%) and 396 (7.12%), respectively. Peri-strut low intensity was observed in
      518 struts (9.31%). CONCLUSIONS: This first-in-man study of the Stellium stent
      shows the promising possibility of bioabsorbable polymeric surface coating
      paclitaxel-eluting stents out to 6 months. The low rate of peri-strut low
      intensity suggests low cellular toxicity of the Stellium stent compared with the
      first-generation DES.

PMID- 20699598
TI  - Relationships of cigarette smoking and alcohol consumption to metabolic syndrome
      in Japanese men.
AB  - BACKGROUND: Cigarette smoking is an important, aggravating factor in metabolic
      syndrome (MetS). In addition, some studies have reported that MetS is related to
      alcohol consumption irrespective of the amount consumed. However, the
      relationship of the combination of the 2 habits to MetS has not been fully
      described. METHODS: In this cross-sectional survey, a questionnaire was used to
      collect information on cigarette smoking and alcohol consumption from 3904
      Japanese men aged 20 years or older. MetS was defined according to Japanese
      criteria. Logistic regression analysis was used to analyze relationships of
      cigarette smoking and alcohol consumption with MetS, after adjustment for
      potential confounding factors. RESULTS: Among the subjects, 581 (14.9%) had MetS.
      Daily cigarette and alcohol consumption were significantly associated with the
      prevalence of MetS (P < 0.0001, P = 0.030 for trend). The multivariate-adjusted
      odds ratio for the prevalence of MetS was 1.89 (95% confidence interval: 1.34
      2.65) for subjects who smoked >=30 cigarettes/day, as compared with nonsmokers;
      1.54 (1.06-2.23) for those who consumed >=69 grams of ethanol/day, as compared
      with nondrinkers; and 3.63 (1.91-6.90) for those who smoked >=30 cigarettes/day
      and consumed >=69 grams of ethanol/day, as compared with those who neither smoked
      nor drank. The interaction of smoking >=30 cigarettes/day with drinking >=69
      grams/day was 2.03 (1.02-4.01, P = 0.043). CONCLUSIONS: Cigarette smoking and
      alcohol drinking had independent relations to the prevalence of MetS. In
      addition, the prevalence of MetS was higher among Japanese men who smoked and
      drank heavily.

PMID- 20699599
TI  - A 4-year study of the association between short sleep duration and change in body
      mass index in Japanese male workers.
AB  - BACKGROUND: Studies of Western populations have shown an inconsistent
      longitudinal association between short sleep duration and change in body mass
      index (BMI); a recent Japanese cohort study reported a significant association in
      men, but over a 1-year period. The aim of this longitudinal study was to examine
      whether this association was robust over a 4-year interval in Japanese men.
      METHODS: A total of 3803 middle-aged Japanese male white-collar workers (mean age
      47.8 years, mean BMI 23.9 kg/m(2)) in Tokyo, Japan, were included in this study
      from 1994-1995 (baseline) to 1998-1999 (follow-up). Height and weight were
      objectively measured at annual health checkups, and other data, including sleep
      duration, were collected using a structured interview. We used linear regression
      models to estimate change in BMI, after adjustment for covariates. The reference
      category for sleep duration was set to 7 hours, to conform with previous studies.
      RESULTS: As compared with participants sleeping 7 hours, those sleeping 5 hours
      or less had a significantly higher BMI at baseline (beta coefficient: 0.34
      kg/m(2), 95% confidence interval (CI): 0.03, 0.65) and gained 0.15 kg/m(2) in BMI
      over 4 years (95% CI: 0.03, 0.27), after adjustment for age, baseline BMI,
      lifestyle behavior, and medication. CONCLUSIONS: The longitudinal association
      between short sleep duration at baseline and relative increase in BMI was
      significant in Japanese male workers over a 4-year interval.

PMID- 20699600
TI  - High blood pressure in obese and nonobese Japanese children: blood pressure
      measurement is necessary even in nonobese Japanese children.
AB  - BACKGROUND: Although the prevalences of obesity and hypertension (HT) are
      increasing in children, there have been few epidemiological studies of HT in
      Japanese children. We evaluated the prevalences of HT and high-normal blood
      pressure (HNBP), and examined the relationship between blood pressure (BP) and
      body mass index (BMI), in Japanese children. METHODS: The subjects of this study
      were 2420 children living in the town of Ina, Saitama Prefecture, Japan during
      the period from 2006 through 2008. Body height, weight, and BP were measured. HT
      and HNBP were defined according to the HT criteria for Japanese children.
      Children with HNBP or HT were defined as having high blood pressure (HBP).
      RESULTS: The prevalences of HBP were 15.9% and 15.8% in fourth-grade boys and
      girls, respectively, and 11.1% and 10.8% in seventh-grade boys and girls,
      respectively. Irrespective of sex or grade level, a higher BMI was associated
      with a higher prevalence of HBP (P < 0.001). When compared with the <50th
      percentile BMI category, the crude odds ratios (ORs) were statistically
      significant for the 75th to 84th percentile category in fourth-grade boys (OR:
      4.54, 95% CI: 2.36-8.76), the >=95th percentile in fourth-grade girls (13.29,
      5.93-29.77), the 85th to 94th percentile (3.16, 1.46-6.84) in seventh-grade boys,
      and the >=95th percentile (7.96, 3.18-19.93) in seventh-grade girls. CONCLUSIONS:
      BMI was associated with HBP in Japanese school children. In addition, some
      children in the lower BMI categories also had HBP.

PMID- 20699601
TI  - Effect of age on the association between body mass index and all-cause mortality:
      the Ohsaki cohort study.
AB  - BACKGROUND: To clarify the effect of age on the association between body mass
      index (BMI) and all-cause mortality. METHODS: We followed 43 972 Japanese
      participants aged 40 to 79 years for 12 years. Cox proportional hazards
      regression analysis was used to estimate hazard ratios (HRs), using the following
      BMI categories: <18.5 (underweight), 18.5-20.9, 21.0-22.9, 23.0-24.9 (reference),
      25.0-27.4, 27.5-29.9, and >=30.0 kg/m(2) (obese). Analyses were stratified by age
      group: middle-aged (40-64 years) vs elderly (65-79 years). RESULTS: We observed a
      significantly increased risk of mortality in underweight elderly men: the
      multivariate HR was 1.26 (0.92-1.73) in middle-aged men and 1.49 (1.26-1.76) in
      elderly men. In addition, we observed a significantly increased risk of mortality
      in obese middle-aged men: the multivariate HR was 1.71 (1.17-2.50) in middle-aged
      men and 1.25 (0.87-1.80) in elderly men. In women, there was an increased risk of
      mortality irrespective of age group in the underweight: the multivariate HR was
      1.46 (0.96-2.22) in middle-aged women and 1.47 (1.19-1.82) in elderly women.
      There was no excess risk of mortality with age in obese women: the multivariate
      HR was 1.47 (0.94-2.27) in middle-aged women and 1.26 (0.95-1.68) in elderly
      women. CONCLUSIONS: As compared with the reference category, obesity was
      associated with a high mortality risk in middle-aged men, whereas underweight,
      rather than obesity, was associated with a high mortality risk in elderly men. In
      women, obesity was associated with a high mortality risk during middle age;
      underweight was associated with a high mortality risk irrespective of age. The
      mortality risk due to underweight and obesity may be related to sex and age.

PMID- 20699602
TI  - Development of a database of health insurance claims: standardization of disease
      classifications and anonymous record linkage.
AB  - BACKGROUND: Health insurance claims (ie, receipts) record patient health care
      treatments and expenses and, although created for the health care payment system,
      are potentially useful for research. Combining different types of receipts
      generated for the same patient would dramatically increase the utility of these
      receipts. However, technical problems, including standardization of disease names
      and classifications, and anonymous linkage of individual receipts, must be
      addressed. METHODS: In collaboration with health insurance societies, all
      information from receipts (inpatient, outpatient, and pharmacy) was collected. To
      standardize disease names and classifications, we developed a computer-aided post
      entry standardization method using a disease name dictionary based on
      International Classification of Diseases (ICD)-10 classifications. We also
      developed an anonymous linkage system by using an encryption code generated from
      a combination of hash values and stream ciphers. Using different sets of the
      original data (data set 1: insurance certificate number, name, and sex; data set
      2: insurance certificate number, date of birth, and relationship status), we
      compared the percentage of successful record matches obtained by using data set 1
      to generate key codes with the percentage obtained when both data sets were used.
      RESULTS: The dictionary's automatic conversion of disease names successfully
      standardized 98.1% of approximately 2 million new receipts entered into the
      database. The percentage of anonymous matches was higher for the combined data
      sets (98.0%) than for data set 1 (88.5%). CONCLUSIONS: The use of standardized
      disease classifications and anonymous record linkage substantially contributed to
      the construction of a large, chronologically organized database of receipts. This
      database is expected to aid in epidemiologic and health services research using
      receipt information.

PMID- 20699604
TI  - Developing a system for regulating expression of human hepatocyte growth factor
      using tetracycline in NRK52E cells.
AB  - INTRODUCTION: Hepatocyte growth factor (HGF) is a target of gene therapy for
      renal fibrosis. The aim of this study was to establish a human HGF gene
      expression system that is regulated by tetracycline (Tet) in normal rat kidney
      tubular epithelial cells (NRK52E cells). MATERIALS AND METHODS: The plasmids pTet
      on, pBI-L-HGF and pTK-Hyg were transfected sequentially into NRK52E cells using
      Lipofectamine 2000. The expression of HGF gene was measured, and the activity of
      expressed HGF was detected. RESULTS: A clone of pBI-L-HGF/NRK52E cells showing
      strong reaction to doxycycline (Dox) was selected using a luciferase reporter
      assay system. The expression of both HGF mRNA and protein was significantly
      higher (both p < 0.01) in the Dox group than that in the control group.
      Furthermore, the bioactivity of expressed HGF was confirmed in the assay.
      CONCLUSIONS: A Tet-regulated human HGF gene expression system in NRK52E cells has
      been established. This cell line may prove useful for gene therapy against renal
      fibrosis.

PMID- 20699603
TI  - Amifostine modulates radio-induced apoptosis of peripheral blood lymphocytes in
      head and neck cancer patients.
AB  - Head and neck cancer is treated mainly with surgery and radiotherapy. Xerostomia
      and mucositis are common adverse effects of radiation therapy. One of the
      strategies aimed at decreasing radiation toxicity is the use of radioprotective
      agents, such as amifostine. We previously reported that radio induced apoptosis
      of peripheral blood lymphocytes was statistically associated with normal tissue
      toxicity in the form of severe xerostomia. The aim of the present study was to
      explore the effects of amifostine on the radiation-induced apoptosis of
      peripheral blood lymphocytes from patients suffering head and neck cancer.
      Eighteen consecutive patients with squamous cell carcinoma of the head and neck
      were included in the study. Peripheral blood lymphocytes were isolated before and
      after the treatment with amifostine. Then, cells were irradiated at 0, 1, 2 and 8
      Gy during 24 hours. Apoptosis was measured by flow cytometry using annexin
      V/propidium iodide. As expected, radio-induced apoptosis values fitted to a semi
      logarithmic equation as follows: RIA = beta ln(Gy) + alpha. The administration of
      amifostine prior to radiation therapy modulates radio-induced apoptosis of
      peripheral blood lymphocytes: 13.68 vs. 13.37 (P = 0.027), 19.11 vs. 17.64 (P =
      0.001) and 30.70 vs. 28.84 (P = 0.001), before and after the administration of
      the drug for 1, 2 and 8 Gy respectively. alpha and beta decreased significantly
      after the administration of the drug: 13.58 vs. 12.99 (P = 0.009) and 8.21 vs.
      7.53 (P = 0.017), respectively. Our results provide new information about the
      biological actions of amifostine in vivo.

PMID- 20699605
TI  - Was fine-needle vasography an obsolete diagnostic method to evaluate ejaculatory
      duct obstruction? Report of 37 cases.
AB  - OBJECTIVES: Based on comparative analyses of the precision as well as reliability
      of the diagnostic results on fine-needle vasography (FNV) and transrectal
      ultrasonography (TRUS) in the diagnosis of patients who were suspected of having
      ejaculatory duct obstruction (EDO), this paper aims to demonstrate whether or not
      FNV techniques still constitute the backbone of diagnostic imaging used in
      obstructive azoospermia of EDO. MATERIALS AND METHODS: From July 2005 to December
      2008, opening fine-needle punctuation and vasography were performed under local
      anesthesia in 37 infertile male patients in our center, all of whom were
      suspected of having bilateral EDO. The diagnostic criteria of these infertile
      males included characteristic changes of TRUS and/or characteristic changes of
      semen analysis. Comparative analyses were made of the diagnostic results of the
      two methods. RESULTS: In the 37 male patients, 19 (51.35%) had been confirmed
      with pathognomonic findings of both semen analyses and TRUS on complete EDO. Of
      the others, 18 patients (48.65%) testified with only pathognomonic findings of
      TRUS but not the typical characteristics on semen analyses. When compared with
      diagnostic results via FNV however, there were only 5 patients (13.51%) who could
      be confirmed as having bilateral EDO, 16/37 showed obstruction of the epididymis
      and proximal vas deferens, 7/37 showed bilateral vasal multiple obstruction, 2
      showed unilateral EDO and multiple obstruction of the contralateral vas deferens,
      and the other 6 patients showed unilateral vasal multiple obstruction and
      obstruction on the contralateral epididymis and proximal vas deferens. Free flow
      of the contrast medium could be defined into the bladder by vasography in 23
      patients. Of the 23 patients, 12 were suspected of having delayed evacuation
      based on more than 50% contrast medium remaining inside their seminal vesicles
      after exhaustion of urine. CONCLUSION: Our analyses suggest that despite its
      advantages of being non-invasive, the diagnostic effect of TRUS is limited by
      both accuracy and reliability. In contrast, although an invasive radiographic
      imaging method, FNV has been proven as being informative when providing
      preoperative details about obstruction and other symptoms. After 3 years of
      research we came to the conclusion that opening fine-needle punctuation and
      vasography have not become outdated, at least recently, and will remain a
      necessary and effective method to identify diseases and to provide a strictly
      defined morphology of the seminal vesicle and ductal system for more
      comprehensive diagnosis of obstructive azoospermia of EDO.

PMID- 20699606
TI  - The role of SRY mutations in the etiology of gonadal dysgenesis in patients with
      45,X/46,XY disorder of sex development and variants.
AB  - BACKGROUND: The potential involvement of SRY in abnormal gonadal development in
      45,X/46,X,der(Y) patients was proposed following the identification of SRY
      mutations in a few patients with Turner syndrome (TS). However, its exact
      etiological role in gonadal dysgenesis in patients with Y chromosome mosaicisms
      has not yet been clarified. AIMS: it was the aim of this study to screen for
      allelic variation in SRY in a large cohort of patients with disorders of sex
      development due to chromosomal abnormalities with 45,X/46,X,der(Y) karyotype.
      PATIENTS: twenty-seven patients, 14 with TS and 13 with mixed gonadal dysgenesis
      (MGD), harboring 45,X/46,X,der(Y) karyotypes were selected. METHODS: Genomic DNA
      was extracted from peripheral blood leukocytes of all patients and from gonadal
      tissue in 4 cases. The SRY coding region was PCR amplified and sequenced.
      RESULTS: We identified only 1 polymorphism (c.561C->T) in a 45,X/46,XY MGD
      patient, which was detected in blood and in gonadal tissue. CONCLUSION: our
      results indicate that mutations in SRY are rare findings in patients with Y
      chromosome mosaicisms. Therefore, a significant role of mutated SRY in the
      etiology of gonadal dysgenesis in patients harboring 45,X/46,XY karyotype and
      variants seems very unlikely.

PMID- 20699607
TI  - Association analysis of genes of the IL19 cluster and their receptors in vitiligo
      patients.
AB  - The aim of the present study was to explore whether the genes encoding
      interleukin (IL) 19, IL-20, IL-24 and 2 chains of the IL-20 receptor type I (IL
      20-RI), IL-20RA and IL-20RB, located on chromosomes 1q32, 6q22-23 and 3q22,
      respectively, are associated with vitiligo. The study involved 76 patients with
      vitiligo and 236 unrelated healthy volunteers. Genomic DNA was extracted from the
      whole blood and the frequencies of 20 single nucleotide polymorphisms were
      analysed by tetraprimer amplification refractory mutation system polymerase chain
      reaction. The minor allele of IL19 rs2243188 was significantly increased in
      vitiligo patients compared to controls (53.3 vs. 28.6%, adjusted p < 0.0001). The
      haplotype analysis revealed associations of 2 IL19/IL20 extended haplotypes
      (AACGTAA and ACCGTAA) and 2 IL20RB haplotypes (AGTA and AGGA) with vitiligo,
      remaining significant after correction for multiple testing. The A-to-C exchange
      at position IL19 rs2243188 leads to the loss of a nuclear receptor subfamily 2
      factor binding site that is thought to influence mouse hippocampal development
      and neuronal differentiation. The third position of the IL20RB haplotypes is
      taken by rs747842 that induces the loss of the interferon regulatory factor 4
      binding site that has an important role in the regulation of innate and adaptive
      immunity and in the signalling of pigmentation as well. In conclusion, the
      present study describes first-time associations between polymorphisms of genes of
      the IL19 cluster and their receptors and vitiligo, indicative of the part of IL19
      and its receptor gene IL20RB in disease pathogenesis.

PMID- 20699608
TI  - Concurrent sarcoidosis and melanoma: coexistence more than by chance?

PMID- 20699610
TI  - Six-minute walk test enhanced by mobile telemetric cardiopulmonary monitoring.
AB  - BACKGROUND: The 6-min walk test (6MWT) is frequently used to assess overall
      cardiopulmonary fitness and to predict outcome, but it yields little diagnostic
      information. Portable telemetric devices allow performing the 6MWT with real-time
      cardiopulmonary monitoring. OBJECTIVES: The study was designed to analyze
      feasibility, safety and clinical usefulness of a mobile cardiopulmonary
      monitoring (MOB)-enhanced 6MWT. METHODS: From August 2003 to June 2007, 261
      consecutive patients with chronic lung and/or heart disease as well as healthy
      controls underwent MOB-enhanced 6MWTs. A subgroup of 33 individuals had the test
      done with and without cardiopulmonary monitoring on independent days. RESULTS: No
      test-related adverse events occurred throughout the study. Whether the 6MWT was
      done without or with cardiopulmonary monitoring (n = 33) did not significantly
      influence the walking distance (WD: 528 +/- 183 vs. 525 +/- 192 m;
      nonsignificant). Fifty-nine percent (155/261) of the patients fulfilled the
      maximal test criteria. Distinct disease-specific exercise response patterns as
      well as treatable co-pathologies were observed. The validity of response patterns
      was better in case of a maximal test. CONCLUSION: An MOB-enhanced 6MWT is
      feasible within daily routine and safe in patients with various diseases. It does
      not negatively affect WD. MOB is a valuable tool to identify factors limiting
      exercise in patients irrespective of their underlying disease.

PMID- 20699611
TI  - Independent information of nonspecific biomarkers in exhaled breath condensate.
AB  - BACKGROUND: Exhaled breath condensate (EBC) has been used for diagnosing and
      monitoring respiratory disorders. For clinical purposes the assessment of easy-to
      obtain nonspecific markers seems particularly interesting. OBJECTIVES: As these
      measures are related to each other, our objective was to extract the independent
      information in global EBC markers across a range of respiratory disorders.
      METHODS: EBC was collected from patients with asthma (n = 18), chronic
      obstructive pulmonary disease (n = 17), and cystic fibrosis (n = 46), as well as
      from lung transplant (LTX) recipients (n = 14) and healthy controls (n = 26).
      Samples were assessed for electrical conductivity, ammonia, pH, and
      nitrite/nitrate. pH was measured after both deaeration with argon and CO(2)
      standardization. Additionally, the fraction of exhaled nitric oxide (FE(NO)) was
      assessed. Factor analysis was applied to identify major factors concerning these
      measures. RESULTS: Three independent factors were detected; the first comprised
      conductivity, ammonia, and pH, especially when standardized using CO(2), the
      second nitrite/nitrate, and the third FE(NO). Conductivity and ammonia were
      highly correlated (r = 0.968; p < 0.001). FE(NO) provided independent information
      mainly in asthma. The nonspecific EBC markers showed considerable overlap between
      patient groups and healthy subjects. However, conductivity, ammonia, pH
      standardized for CO(2) and nitrite/nitrate were increased in LTX recipients
      compared to healthy controls (p < 0.05 each). CONCLUSIONS: A panel of nonspecific
      easy-to-obtain exhaled breath markers could be reduced to 3 independent factors.
      The information content of conductivity, ammonia, and pH after CO(2)
      equilibration appeared to be similar, while FE(NO) was independent. The increased
      levels of these biomarkers in LTX might indicate a potential for their use in
      these patients.

PMID- 20699612
TI  - Increased adipose tissue expression of proinflammatory CD40, MKK4 and JNK in
      patients with very severe chronic obstructive pulmonary disease.
AB  - BACKGROUND: CD40, a transmembrane receptor of the tumor necrosis factor gene
      superfamily, is activated in response to cellular stress, including hypoxia, and
      orchestrates the process of inflammation via secondary messengers such as mitogen
      activated protein kinase kinase 4 (MKK4) and c-Jun NH(2)-terminal kinases (JNK).
      OBJECTIVES: We hypothesized that CD40, MKK4 and JNK expression is increased in
      the adipose tissue of patients with very severe chronic obstructive pulmonary
      disease (COPD). METHODS: In 20 patients with stable COPD, lung function was
      assessed using body plethysmography, and samples of subcutaneous adipose tissue
      were analyzed using real-time PCR. Body composition, including fat mass index
      (FMI), was assessed by bioelectrical impedance. RESULTS: 12 patients in GOLD
      stage I-III (age 61.6 +/- 8.6 years, 4 females, mean partial pressure of oxygen
      in arterial blood, PaO(2), 9.38 +/- 0.21 kPa) were compared to 8 patients in GOLD
      stage IV (age 62.6 +/- 6.3 years, all male, mean PaO(2) 7.70 +/- 0.37 kPa).
      Compared to patients in GOLD stage I-III, patients in GOLD stage IV had lower FMI
      (p = 0.004), being associated with significantly higher adipose tissue expression
      of CD40, MKK4 and JNK [DeltaDeltaCt: 2.55 (1.99, 4.40) vs. 1.87 (1.63, 2.23), p =
      0.013; 5.19 (3.13, 5.96) vs. 2.98 (2.82, 3.86), p = 0.002; 9.01 (5.12, 11.41) vs.
      4.65 (4.42, 6.26), p = 0.001, respectively]. Log-transformed CD40, MKK4 and JNK
      expression was significantly inversely related to PaO(2), respectively.
      CONCLUSIONS: Upregulation of proinflammatory CD40, MKK4 and JNK gene expression
      in adipose tissue in very severe COPD raises the possibility of a role of chronic
      systemic hypoxia in the pathogenesis of adipose tissue inflammation in COPD.

PMID- 20699613
TI  - Eradication of Helicobacter pylori infection aids with the outcome of motion
      sickness adaptation.
AB  - INTRODUCTION: Airsickness affects many aviators, especially at the beginning of
      their flight training. From the symptoms of airsickness, stomach awareness and
      nausea are among the most common and unpleasant. Helicobacter pylori infection of
      the gastric mucosa is a common cause of gastrointestinal symptoms in the general
      population, although it has seldom been associated with motion sickness in the
      scientific literature. METHODS: A retrospective review was conducted in all cases
      of pilot trainees taking basic flight training who were referred to the Hellenic
      Air Force Aeromedical Center due to airsickness and tested for H. pylori, for the
      time period 1996-2005. We compared the H.-pylori-positive pilots with the
      uninfected ones according to their responses to the habituation sorties and
      subsequent completion of the basic flight training as a whole. A statistical
      analysis was performed using Fisher's exact test. RESULTS: The findings of the
      study suggest that diagnosing H. pylori infection and treating it with
      eradication therapy increases the possibility of a pilot trainee successfully
      completing the habituation flights, while it does not affect success in the basic
      flight training as a whole. CONCLUSIONS: Eradication therapy for H. pylori may
      provide a temporary reduction in reported nausea during flight training. The
      findings are not conclusive, but highly suggestive of a pathophysiologic link
      between H. pylori and motion sickness, needing further clarification through
      targeted studies.

PMID- 20699614
TI  - Formation of caries-like lesions in vitro on the root surfaces of human teeth in
      solutions simulating plaque fluid.
AB  - Lesion formation on root surfaces of human posterior teeth was studied in
      acetate/lactate buffers with a background electrolyte composition based on plaque
      fluid analyses. Lesion depth after 28 days at 37 degrees C was measured in
      relation to: the presence or absence of cementum; the concentration of
      undissociated buffer; the presence or absence of magnesium ions at plaque fluid
      concentration. Each factor was evaluated at several values of -log(ion activity
      product for hydroxyapatite): pI(HA). Solutions were formulated to minimize
      variation in pH, which varied by < or =0.03 for a given comparison (individual
      pI(HA)) and by 0.42-0.82 over the range of pI(HA) within experiments. Lesions on
      surfaces from which cementum had been ground were significantly deeper than on
      intact surfaces, but this is considered to be due to subsurface mechanical damage
      and not to a solubility difference. Neither the concentration of undissociated
      buffer nor the presence of magnesium ions significantly affected lesion depth.
      Lesion depth was strongly influenced by the correlated variations in pI(HA) and
      pH. At pI(HA) 54 and 55, only extremely shallow lesions formed. From pI(HA) 56,
      lesion depth increased with increasing pI(HA). The results confirm that the
      solubility of the mineral of root tissues is higher than that of hydroxyapatite,
      but indicate that it is probably lower than suggested by Hoppenbrouwers et al.
      [Arch Oral Biol 1987;32:319-322]. For calcium concentrations of 3-12 mM, the
      critical pH for root tissue mineral was calculated as 5.22-5.66 assuming
      solubility equivalent to pI(HA) 54 and 5.08-5.51 assuming pI(HA) 55.

PMID- 20699615
TI  - Effects of various fluoride solutions on enamel erosion in vitro.
AB  - The objective of this in vitro study was to investigate the effect of different
      fluoride solutions on enamel erosion. Human enamel specimens were pretreated with
      1 of 10 different fluoride solutions (n = 20): TiF(4), NaF, AmF, ZnF(2), or
      SnF(2), each at native pH (pH range: 1.2-7.8) or buffered pH (pH = 4). The
      control group samples received no fluoride pretreatment. All samples were then
      eroded by citric acid (pH 2.6) for 6 x 1 min daily over 5 days. Between the
      erosive cycles, the samples were stored in artificial saliva. Erosion effects
      were investigated by surface profilometry (n = 10), scanning electron microscopy
      (n = 4), and energy-dispersive X-ray spectroscopy (n = 6) after fluoride
      pretreatment and after erosion. To test the effects of pH only, additional
      experiments were carried out with fluoride-free solutions at similar pH to that
      of fluoride solutions. In general, AmF solution was more effective in protecting
      enamel erosion compared to all other fluoride agents. However, the application of
      native TiF(4), native and buffered SnF(2), and native and buffered AmF solutions
      also resulted in significantly less enamel loss compared to the control group. A
      Ti-rich coating was formed after application of native TiF(4), but partially
      dissolved due to erosive attack. Samples pretreated with SnF(2) showed a
      significant increase in surface tin content. Surface fluoride concentration was
      significantly increased by native TiF(4), native and buffered AmF, buffered
      ZnF(2), and buffered NaF application. Under the current experimental setting, the
      fluoride agents at lower pH had better protective potential. Highly concentrated
      TiF(4), AmF, and SnF(2) solution was effective in inhibiting erosion of enamel.

PMID- 20699616
TI  - Injury of the spino-thalamo-cortical pathway is necessary for central post-stroke
      pain.
AB  - OBJECTIVES: We investigated the relationship between injury of the spino-thalamo
      cortical pathway (STP) and central post-stroke pain (CPSP) in patients with
      intracerebral hemorrhage, using diffusion tensor tractography (DTT). METHODS: 30
      consecutive chronic patients, in whom integrity of the STP and the medial
      lemnisco-thalamo-cortical pathway (MLP) were spared in both hemispheres, were
      recruited. We classified the patients into two groups according to the presence
      of the CPSP. DTTs were obtained using the FMRIB Software Library. Fractional
      anisotropy (FA), mean diffusivity (MD), and tract volume were measured. A
      laterality index (LI) was used to determine asymmetry of DTT parameters between
      the hemispheres. RESULTS: The LI for tract volume of the STP in the CPSP group
      was lower than that of the non-CPSP group (p = 0.000). However, there were no
      differences between the CPSP group and non-CPSP group for the LIs of FA or MD of
      the STP or for the LIs of FA, MD, or tract volume of the MLP (p > 0.05).
      CONCLUSIONS: Decrease of tract volume without changes in the STP FA or MD values
      in the CPSP group indicates partial injury of STP. Therefore, injury of the STP
      seems to be a requirement for the development of CPSP in patients with
      intracerebral hemorrhage.

PMID- 20699617
TI  - Tacrolimus-associated posterior reversible encephalopathy syndrome after solid
      organ transplantation.
AB  - Tacrolimus (TAC) is an immunosuppressant drug discovered in 1984 by Fujisawa
      Pharmaceutical Co., Ltd. This drug belongs to the group of calcineurin
      inhibitors, which has been proven highly effective in preventing acute rejection
      after transplantation of solid organs. However, neurotoxicity and nephrotoxicity
      are its major adverse effects. Posterior reversible encephalopathy syndrome
      (PRES) is the most severe and dramatic consequence of calcineurin inhibitor
      neurotoxicity. It was initially described by Hinchey et al. in 1996 [N Engl J Med
      1996;334:494-450]. Patients typically present with altered mental status,
      headache, focal neurological deficits, visual disturbances, and seizures.
      Magnetic resonance imaging is the most sensitive imaging test to detect this.
      With the more deep-going studies done recently, we have learnt more about this
      entity. It was noted that this syndrome is frequently reversible, rarely limited
      to the posterior regions of the brain, and often located in gray matter and
      cortex as well as in white matter. Therefore, in this review, the focus is on the
      current understanding of clinical recognition, pathogenesis, neuroimaging and
      management of TAC-associated PRES after solid organ transplantation.

PMID- 20699618
TI  - Definitions of types of hearing impairment: a discussion paper.
AB  - OBJECTIVE: To develop a clear and meaningful set of definitions of types of
      hearing impairment. METHOD: A critical analysis was made of previous definitions
      together with a consideration of current knowledge of functions and dysfunctions
      of the auditory system. RESULTS AND CONCLUSIONS: A coherent set of definitions
      compatible with the contemporary understanding of auditory disorders and their
      perceptual effects is proposed.

PMID- 20699619
TI  - Expression of genes involved in lipid metabolism in men with impaired glucose
      tolerance: impact of insulin stimulation and weight loss.
AB  - BACKGROUND: The impaired glucose tolerance (IGT) state is characterized by
      insulin resistance. Disturbances in fatty acid (FA) metabolism may underlie this
      reduced insulin sensitivity. The aim of this study was to investigate whether the
      prediabetic state is accompanied by changes in the expression of genes involved
      in FA handling during fasting and in insulin-mediated conditions and to study the
      impact of weight loss. METHODS: Seven IGT men and 5 men with normal glucose
      tolerance (NGT), comparable in terms of age and BMI, participated in the study.
      The 5 IGT men followed a 12-week weight loss program. Muscle biopsies were taken
      and the expression of 6 genes was investigated. RESULTS: Subjects had a reduction
      of 15.5 +/- 4.3 kg in body weight. Baseline gene expression was not different
      between NGT and IGT men. After a hyperinsulinemic clamp, there was an overall
      upregulation of PGC1alpha, SREBP-1c, SREBP-2, and ACC-2. The upregulation of
      SREBP-2 was more pronounced in IGT men (p = 0.049). Weight loss significantly
      increased insulin sensitivity by 71%, which was not reflected in altered gene
      expression profiles. CONCLUSIONS: SREBP-2 shows altered insulin responsiveness in
      IGT men compared with NGT men, while there were no differences in basal gene
      expression.

PMID- 20699620
TI  - Comparative effectiveness of paricalcitol versus cinacalcet for secondary
      hyperparathyroidism in patients receiving hemodialysis.
AB  - BACKGROUND/AIMS: Parathyroidectomies are performed when medical therapy fails to
      control secondary hyperparathyroidism in hemodialysis patients. The objective of
      this study was to compare parathyroidectomy rates in secondary
      hyperparathyroidism patients treated with paricalcitol or cinacalcet. METHODS:
      Retrospective cohort study using health insurance claims from January 2001
      through June 2007 for adult hemodialysis patients who were new users of
      paricalcitol or cinacalcet. Subjects had a minimum of 12 months' enrollment prior
      to initiation of treatment and at least 30-day follow-up. RESULTS: We identified
      1,387 paricalcitol- and 1,317 cinacalcet-treated patients. The parathyroidectomy
      incident rate was 74% lower in the paricalcitol (0.58 per 100 patient-years)
      compared to the cinacalcet (2.24 per 100 patient-years) cohort, with an
      unadjusted rate ratio of 0.26 (95% CI 0.12-0.52). The time to parathyroidectomy
      from medication initiation was longer for paricalcitol than cinacalcet; however,
      it was not statistically significant (535 vs. 443 days, p = 0.377). A Cox
      proportional hazard model that adjusted for age, gender, obesity, significantly
      different comorbidities, and duration of hemodialysis resulted in an adjusted
      risk reduction for parathyroidectomy of 79% (HR = 0.21, 95% CI 0.10-0.46) for
      paricalcitol compared to cinacalcet. CONCLUSION: These data suggest that long
      term treatment with paricalcitol is associated with fewer parathyroidectomies
      when compared to cinacalcet. Further comparative studies are needed to validate
      these results.

PMID- 20699621
TI  - Urinary type IV collagen in nondiabetic kidney disease.
AB  - BACKGROUND: Type IV collagen is one of the major components of basement membrane.
      In diabetic nephropathy, it is already known that urinary excretion of type IV
      collagen increases with the disease progression. However, in nondiabetic kidney
      disease, urinary type IV collagen (u-IVc) levels have not been extensively
      investigated. The aim of this study was to evaluate u-IVc levels in various
      nephropathies except diabetic nephropathy. METHODS: u-IVc levels were measured
      cross-sectionally from 527 biopsy-proven nondiabetic renal disease patients at
      tertiary care hospitals by one-step sandwich enzyme immunoassay. RESULTS: On
      simple regression analyses, u-IVc levels had positive correlation with age, blood
      pressure, urinary protein (u-Prot), urinary beta(2) microglobulin, urinary N
      acetyl-beta-D-glucosaminidase, HbA(1)c, and selectivity index (SI), while u-IVc
      had negative correlation with eGFR and serum albumin. Multiple regression
      analyses revealed that u-IVc was positively correlated with u-Prot, HbA(1)c and
      SI. Among biopsy-proven nondiabetic nephropathies, elevation of u-IVc was
      distinctively observed in membranous nephropathy and anti-neutrophil cytoplasmic
      antibody (ANCA)-associated glomerulonephritis. CONCLUSION: u-IVc levels were
      elevated with the increase in u-Prot, HbA(1)c and SI. In addition, among
      nondiabetic kidney disease, elevation of u-IVc was observed in patients with
      membranous nephropathy and ANCA, which might reflect the thickening of basement
      membrane or severe kidney damage.

PMID- 20699623
TI  - The standardized uptake value of 18-fluorodeoxyglucose positron emission
      tomography after chemoradiation and clinical outcome in patients with localized
      gastroesophageal carcinoma.
AB  - BACKGROUND: Empirical trimodality (TM) or bimodality (BM) approaches lead to
      unpredictable outcomes in patients with localized gastroesophageal carcinoma
      (LGC). We hypothesized that the standardized uptake value (SUV) of positron
      emission tomography (PET) after chemoradiation would define the clinical outcome
      in patients. METHODS: We analyzed 272 (TM = 155 and BM = 117) LGC patients after
      chemoradiation PET and studied its association with overall survival (OS) and
      disease-free survival (DFS). The log-rank test, multivariate Cox proportional
      hazards model, and Kaplan-Meier survival plots were used to analyze the
      dichotomized data (using the median as a cutoff). RESULTS: The median survival of
      TM patients was 49 months (95% CI: 36 to not reached) and that of BM patients was
      20 months (95% CI: 15-34; p < 0.0001); however, if the postchemoradiation SUV was
      <4.6 (4.6 = median SUV), the OS of TM and BM patients was not significantly
      different (p = 0.22). In the multivariate Cox model, postchemoradiation SUV (p =
      0.02), baseline stage (p = 0.03), histology grade (p = 0.01), and having surgery
      (p = 0.004) were independent prognosticators for OS and DFS. CONCLUSIONS: These
      data document that the low postchemoradiation SUV in both TM and BM patients
      defines clinical aggression and has a similar clinical outcome. Systematic
      validation of PET changes, in this setting, can facilitate individualization of
      therapy of LGC patients.

PMID- 20699622
TI  - Smoking cessation: an integral part of lung cancer treatment.
AB  - Lung cancer is the leading cause of cancer death in the US. About 50% of lung
      cancer patients are current smokers at the time of diagnosis and up to 83%
      continue to smoke after diagnosis. A recent study suggests that people who
      continue to smoke after a diagnosis of early-stage lung cancer almost double
      their risk of dying. Despite a growing body of evidence that continued smoking by
      patients after a lung cancer diagnosis is linked with less effective treatment
      and a poorer prognosis, the belief prevails that treating tobacco dependence is
      useless. With improved cancer treatments and survival rates, smoking cessation
      among lung cancer patients has become increasingly important. There is a pressing
      need to clarify the role of smoking cessation in the care of lung cancer
      patients. OBJECTIVE: This paper will report on the benefits of smoking cessation
      for lung cancer patients and the elements of smoking cessation treatment, with
      consideration of tailoring to the needs of lung cancer patients. RESULTS: Given
      the significant benefits of smoking cessation and that tobacco dependence remains
      a challenge for many lung cancer patients, cancer care providers need to offer
      full support and intensive treatment with a smoking cessation program that is
      tailored to lung cancer patients' specific needs. CONCLUSION: A tobacco
      dependence treatment plan for lung cancer patients is provided.

PMID- 20699624
TI  - Efficacy of S-1 in patients with castration-resistant prostate cancer: a phase II
      study.
AB  - OBJECTIVES: This study was conducted to evaluate the efficacy and safety of S-1,
      an oral fluoropyrimidine derivative, in Japanese patients with castration
      resistant prostate cancer (CRPC). The primary endpoint was prostate-specific
      antigen (PSA) response. METHODS: In this open-label phase II study, S-1 was
      started at a dose of 80, 100 or 120 mg daily based on body surface area (BSA) for
      28 days, followed by 14 days of rest. Patients with histological proof of
      prostate cancer refractory to hormonal therapies were eligible. Patients who
      received prior chemotherapy were excluded. All patients provided written informed
      consent. To observe 20% confirmed PSA response, 33 assessable patients were
      needed. Treatment was continued until disease progression or the development of
      intolerable toxicity. RESULTS: A total of 35 eligible patients were enrolled. The
      median number of treatment cycles was 3. PSA response was observed in 8 patients
      (22.9%, 90% CI 11.9-37.5), including 3 in which (8.6%) the PSA level normalized.
      The median overall survival was 25.4 months. The most common treatment-related
      grade 3 toxicity was anorexia (14.3%). There was no death during the study.
      CONCLUSION: S-1 monotherapy is active against castration-resistant prostate
      cancer and has acceptable toxicity.

PMID- 20699625
TI  - Retinal and ocular toxicity in ocular application of drugs and chemicals--part
      II: retinal toxicity of current and new drugs.
AB  - AIMS: Retinal pharmacotherapy has gained great importance for the treatment of
      various retinal diseases. An increasing number of drugs have been constantly
      released into the market, especially for wet age-related macular disease and
      diabetic macular edema. In this review, the issues concerning the toxicity of
      current and new classes of drugs are discussed. METHODS: An extensive search of
      the literature was performed to review various aspects of drug toxicity in
      retinal pharmacotherapy. The different major classes of drugs, such as
      corticosteroids, antibiotics, antimetabolites, antineoplastic agents, monoclonal
      antibodies (mAbs), nonsteroidal anti-inflammatory drugs, enzymes, fibrinolytics,
      miscellaneous anti-inflammatory and antiangiogenic agents, as well as toxicity
      unrelated to the drug were identified and discussed. RESULTS: Corticosteroids
      like fluocinolone, dexamethasone or triamcinolone at low dose cause little damage
      to the retina, but at high doses signs of toxicity have been well documented.
      Complications like cataract and glaucoma are quite common with corticosteroids.
      Aminoglycosides showed differences in the type and doses associated with toxic
      reactions, thereby the following order of toxicity can be described (from most
      toxic to least toxic): gentamicin > netilmicin = tobramycin > amikacin =
      kanamycin. Vancomycin at the usual dose of 1 mg is not toxic to the retina, while
      further studies are necessary in order to clarify the safety of new-generation
      quinolones. 5-Fluorouracil has been shown to be nontoxic to the retina after an
      injection of 2.5 mg in animals. mAbs like ranibizumab and bevacizumab were
      demonstrated to be safe to the retina in cell culture, animals and humans at high
      doses. The exact biocompatibility of nonsteroidal anti-inflammatory agents like
      diclofenac needs further evaluation. Preservatives like benzyl alcohol and
      changes in pH or osmolarity exert an influence on the toxic effects of
      intravitreally applied drugs. CONCLUSIONS: A great number of drugs are now used
      mainly intravitreally without relevant retinal toxicity.

PMID- 20699626
TI  - Drug-induced secondary cataract prevention: experimental ex vivo and in vivo
      results with disulfiram, methotrexate and actinomycin D.
AB  - BACKGROUND/AIMS: A clinical approach to prevent secondary cataract after lens
      implantation involves the intraocular application of pharmacological agents. The
      goals of our study were to develop an ex vivo model to test the drug
      effectiveness for lens epithelial cell ablation from the basal membrane and to
      verify the data in rabbit intraocular lens implantation experiments. METHODS:
      Human capsular rhexis specimens were incubated with drugs and the residual cells
      were differentiated by use of the Live-Dead assay and quantified by staining with
      Hoechst dye. After phakoemulsification of rabbit eyes and before intraocular lens
      implantation, capsular bags were filled with drug-loaded hyaluronic acid for 5
      min. RESULTS: An ex vivo model was established which allows the testing of drugs
      on lens epithelial cell ablation. Drug treatment reduced the number of viable
      cells on the specimens drastically, ranging between 0.44 +/- 0.53% (6.0 +/- 7.3
      cells/mm2) for disulfiram, 0.27 +/- 0.50% (3.7 +/- 6.9 cells/mm2) for
      methotrexate and 0.07 +/- 0.19% (0.1 +/- 0.27 cells/mm2) for actinomycin D.
      Rabbit eyes treated with a mixture of methotrexate/actinomycin D showed no
      posterior capsule opacification at 4 months and a low opacification 6 months
      postoperatively. Without drug treatment low opacification starts 6 weeks
      postoperatively. CONCLUSIONS: The drug screening in the described ex vivo model
      can help to reduce the number of preclinical studies for secondary cataract
      prevention. The successful ex vivo cell ablation by methotrexate/actinomycin D
      was confirmed by a delayed in vivo secondary cataract formation.

PMID- 20699627
TI  - Choroidal neovascular membranes express toll-like receptor 3.
AB  - BACKGROUND: Recent evidence has suggested a role for toll-like receptor 3 (TLR3)
      in experimental models of age-related macular degeneration (AMD). To date,
      however, few data exist about TLR3 in human AMD. The purpose of this study was to
      investigate the expression of TLR3 in human choroidal neovascular (CNV)
      membranes. METHODS: Immunostaining for TLR3 was performed on sections of CNV
      membranes from 8 AMD patients and eyes from 4 donors without CNV. RESULTS: All
      CNV membranes expressed TLR3 in retinal pigment epithelial (RPE) cells. One was
      classified as having strong intensity, 5 as having moderate intensity and 2 as
      having weak intensity. All cases had >=30% of the RPE cells staining for TLR3,
      ranging from 30 to 90%. No expression of TLR3 was observed in vascular
      endothelial cells or fibroblasts in any CNV membrane. In the donor eyes, the RPE
      cells near the ora serrata stained stronger than those at the posterior pole,
      where no staining was observed in 3 out of 4 cases. CONCLUSION: TLR3 was found in
      all CNV membranes and was expressed exclusively in RPE cells. The observed
      difference in RPE staining for TLR3 in donor eyes and CNV membranes suggests a
      possible role for this receptor in human neovascular AMD.

PMID- 20699628
TI  - Effect of black-currant extract on negative lens-induced ocular growth in chicks.
AB  - AIM: To evaluate the effects of orally administered black-currant (BC) extract on
      the enlargement of globe component dimensions induced in chicks by wearing
      negative lenses. METHODS: Negative lenses (-8 D) were worn on the right eyes by 8
      day-old chicks, and their fellow eyes acted as controls. BC extract and distilled
      water (vehicle control) were orally administered once a day for 3 days. To
      confirm the effect of BC anthocyanins (BCAs), they were intravenously
      administered once a day for 3 days. Dimensions of globe components of right eyes
      and fellow eyes were measured with an A-scan ultrasound instrument on the third
      day (day 4) after placement of the negative lenses. RESULTS: Orally administered
      BC extract significantly inhibited enlargement of vitreous-chamber depth, axial
      and ocular lengths in a dose-dependent manner when compared to controls.
      Intravenously administered BCAs also inhibited elongation of vitreous-chamber
      depth and axial length when compared to controls. CONCLUSIONS: This is the first
      evidence that BC extract and BCAs could inhibit enlargement of globe component
      dimensions in a negative lens-induced chick myopia model.

PMID- 20699629
TI  - Comparative study of Gram stain, potassium hydroxide smear, culture and nested
      PCR in the diagnosis of fungal keratitis.
AB  - OBJECTIVE: This study seeks to evaluate the efficacy and practicality of the
      molecular method, compared to the standard microbiological techniques for
      diagnosing fungal keratitis (FK). METHODS: Patients with eye findings suspected
      of FK were enrolled for cornea sampling. Scrapings from the affected areas of the
      infected corneas were obtained and were divided into two parts: one for smears
      and cultures, and the other for nested PCR analysis. RESULTS: Of the 38 eyes, 28
      were judged to have fungal infections based on clinical and positive findings in
      the culture, smear and responses to antifungal treatment. Potassium hydroxide,
      Gram staining, culture and nested PCR results (either positive or negative)
      matched in 76.3, 42.1, 68.4 and 81.6%, respectively. CONCLUSION: PCR is a
      sensitive method but due to the lack of sophisticated facilities in routine
      laboratory procedures, it can serve only complementarily and cannot replace
      conventional methods.

PMID- 20699630
TI  - Unexpected insensitivity of the cholinergic motor responses to morphine in the
      human small intestine.
AB  - BACKGROUND/AIMS: morphine is known to inhibit cholinergic contractions of the
      guinea pig small intestine. This has been compared to the human small intestinal
      innervated longitudinal muscle in the current study. METHODS: cholinergic primary
      contractions of human small intestinal longitudinal strips were evoked by
      electrical field stimulation (EFS; 0.5- 5 Hz in the presence of purinergic and
      nitrergic blockers or 5 Hz without pretreatment) and recorded isotonically in
      organ bath experiments. Guinea pig small intestinal segments were also studied.
      RESULTS AND CONCLUSION: neurogenic cholinergic contractions of human preparations
      were unaffected by morphine (1, 2 or 10 micromol/l). Longitudinal contractions of
      the guinea pig ileum were concentration-dependently suppressed by morphine (0.1
      10 micromol/l). It is concluded that myenteric neurons supplying the longitudinal
      muscle of the human small intestine are much less sensitive to morphine than
      those of the guinea pig.

PMID- 20699631
TI  - Role of 20-hydroxyeicosatetraenoic and epoxyeicosatrienoic acids in the
      regulation of vascular function in a model of hypertension and endothelial
      dysfunction.
AB  - The objective of this study was to determine if acute inhibition of 20
      hydroxyeicosatetraenoic acid (20-HETE) synthesis or reduced inactivation of
      epoxyeicosatrienoic acids (EETs) can correct L-N(G)-nitro-arginine-methyl-ester
      (L-NAME)-induced abnormal vascular reactivity in the perfused mesenteric bed and
      the carotid artery of spontaneously hypertensive rats (SHR). Administration of L
      NAME in drinking water (80 mg/l) to SHR for 3 weeks resulted in abnormal vascular
      reactivity to norepinephrine and carbachol in the perfused mesenteric vascular
      bed and carotid artery, and significantly elevated mean arterial blood pressure
      (244 +/- 9 mm Hg) as compared to SHR controls drinking regular water (176 +/- 3
      mm Hg). In the perfused mesenteric vascular bed, the impaired vascular
      responsiveness to norepinephrine was corrected by acute treatment with N-hydroxy
      N'-(4-butyl-2-methylphenyl)formamidine (HET0016), an inhibitor of 20-HETE
      formation, but not by 1-cyclohexyl-3-dodecyl urea (CDU), an inhibitor of soluble
      epoxide hydrolase. Treatment with either HET0016 or CDU did not improve impaired
      carbachol-induced vasodilation in the perfused mesenteric vascular bed. In the
      isolated carotid artery, treatment with HET0016 corrected the L-NAME-induced
      increase in norepinephrine-induced vasoconstriction, whereas only CDU treatment
      could improve impaired carbachol-induced vasodilation. Results of this study
      indicate that vascular function in a state of compromised nitric oxide formation
      is differentially modulated by 20-HETE and EETs, and that treatment with HET0016
      or CDU may improve vascular function in a state of high blood pressure and
      endothelial dysfunction.

PMID- 20699632
TI  - Impairment of aerobic glycolysis by inhibitors of lactic dehydrogenase hinders
      the growth of human hepatocellular carcinoma cell lines.
AB  - BACKGROUND/AIMS: by reducing the number of ATP molecules produced via aerobic
      glycolysis, the inhibition of lactic dehydrogenase (LDH) should hinder the growth
      of neoplastic cells without damaging the normal cells which do not rely on this
      metabolic pathway for their energetic needs. Here, we studied the effect of
      oxamic and tartronic acids, 2 inhibitors of LDH, on aerobic glycolysis and cell
      replication of HepG2 and PLC/PRF/5 cells, 2 lines from human hepatocellular
      carcinomas. METHODS: aerobic glycolysis was measured by calculating the amounts
      of lactic acid formed. The effect on replication was assessed by culturing the
      cells in both standard conditions and glucose-deprived medium, which was used to
      shut down aerobic glycolysis. RESULTS: the oxamic and tartronic acids inhibited
      aerobic glycolysis, impaired the growth of both cell lines and also induced an
      increased expression of p53-upregulated modulator of apoptosis, a signal of cell
      death. A strong impairment of cell replication by oxamic acid was only found when
      the cells were cultured in the presence of glucose, indicating that it was for
      the most part owing to inhibition of aerobic glycolysis. CONCLUSIONS: inhibition
      of aerobic glycolysis achieved by blocking LDH could be useful in the treatment
      of human hepatocellular carcinomas. Without interfering with glucose metabolism
      in normal cells, it could hinder cell growth by itself and could also enhance the
      chemotherapeutic index of associated anticancer agents by decreasing the levels
      of ATP selectively in neoplastic cells.

PMID- 20699633
TI  - High-throughput siRNA screens using gammaH2AX as marker uncover key regulators of
      genome integrity in mammalian cells.

PMID- 20699634
TI  - Extrapleural pneumonectomy, photodynamic therapy and intensity modulated
      radiation therapy for the treatment of malignant pleural mesothelioma.
AB  - Intensity modulated radiation therapy (IMRT) has recently been proposed for the
      treatment of malignant pleural mesothelioma (MPM). Here, we describe our
      experience with a multimodality approach for the treatment of mesothelioma,
      incorporating extrapleural pneumonectomy, intraoperative photodynamic therapy and
      postoperative hemithoracic IMRT. From 2004-2007, we treated 11 MPM patients with
      hemithoracic IMRT, 7 of whom had undergone porfimer sodium-mediated PDT as an
      intraoperative adjuvant to surgical debulking. The median radiation dose to the
      planning treatment volume (PTV) ranged from 45.4-54.5 Gy. For the contralateral
      lung, V20 ranged from 1.4-28.5%, V5 from 42-100% and MLD from 6.8-16.5 Gy. In our
      series, 1 patient experienced respiratory failure secondary to radiation
      pneumonitis that did not require mechanical ventilation. Multimodality therapy
      combining surgery with increased doses of radiation using IMRT, and newer
      treatment modalities such as PDT , appears safe. Future prospective analysis will
      be needed to demonstrate efficacy of this approach in the treatment of malignant
      mesothelioma. Efforts to reduce lung toxicity and improve dose delivery are
      needed and provide the promise of improved local control and quality of life in a
      carefully chosen multidisciplinary approach.

PMID- 20699635
TI  - You are what you express: glutamatergic neurogenesis in the adult SVZ.

PMID- 20699636
TI  - Releasing the brake on presynaptic development: Cdc20-APC triggers NeuroD2
      degradation to drive presynaptic differentiation.

PMID- 20699637
TI  - Channel triage: Emerging insights into the processing and quality control of hERG
      potassium channels by DnaJA proteins 1, 2 and 4.

PMID- 20699638
TI  - A conserved alternative splicing event in plants reveals an ancient exonization
      of 5S rRNA that regulates TFIIIA.
AB  - Uncovering conserved alternative splicing (AS) events can identify AS events that
      perform important functions. This is especially useful for identifying premature
      stop codon containing (PTC) AS isoforms that may regulate protein expression by
      being targets for nonsense mediated decay. This report discusses the
      identification of a PTC containing splice isoform of the TFIIIA gene that is
      highly conserved in land plants. TFIIIA is essential for RNA Polymerase III-based
      transcription of 5S rRNA in eukaryotes. Two independent groups have determined
      that the PTC containing alternative exon is ultraconserved and is coupled with
      nonsense-mediated mRNA decay. The alternative exon appears to have been derived
      by the exonization of 5S ribosomal RNA (5S rRNA) within the gene of its own
      transcription regulator, TFIIIA. This provides the first evidence of ancient
      exaptation of 5S rRNA in plants, suggesting a novel gene regulation model
      mediated by the AS of an anciently exonized non-coding element.

PMID- 20699639
TI  - Reactivating the ARF-p53 axis in AML cells by targeting ULF.
AB  - The tumor suppressor ARF plays an essential role in the cellular response to
      oncogenic stress mainly through activation of p53. Nucleophosmin (NPM), a
      multifunctional protein, forms a stable protein complex with ARF in the nucleolus
      and protects ARF from the proteasome-mediated degradation. Notably, NPM is
      mutated in about one third of acute myeloid leukaemia (AML) patients and these
      mutations lead to aberrant cytoplasmic dislocation of nucleophosmin (NPM-c).
      Cytoplasmic NPM mutants lose their abilities to retain ARF in the nucleolus and
      fail to stabilize ARF. Thus, activation of the ARF-p53 axis is significantly
      compromised in these AML cells. We have recently identified the ubiquitin ligase
      of ARF (ULF) as a key factor that controls ARF turnover in human cells. Here, we
      found that the steady levels of both ARF and p53 are very low in human acute
      myeloid leukaemia OCI-AML3 cells expressing cytoplamsic dislocated nucleophosmin
      (NPM-c). As expected, ARF is very unstable and rapidly degraded by proteasome.
      Nevertheless, ULF knockdown stabilizes ARF and reactivates p53 responses in these
      AML cells. These results further demonstrate that ULF is a bona fide E3 ligase
      for ARF and also suggest that ULF is an important target for activating the ARF
      p53 axis in human AML cells.

PMID- 20699640
TI  - A role of small heat shock protein B8 (HspB8) in the autophagic removal of
      misfolded proteins responsible for neurodegenerative diseases.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease
      characterized by the progressive loss of upper and lower motor neurons. As with
      other age-dependent neurodegenerative disorders, ALS is linked to the presence of
      misfolded proteins that may perturb several intracellular mechanisms and trigger
      neurotoxicity. Misfolded proteins aggregate intracellularly generating insoluble
      inclusions that are a key neuropathological hallmark of ALS. Proteins involved in
      the intracellular degradative systems, signaling pathways and the human TAR DNA
      binding protein TDP-43 are major components of these inclusions. While their role
      and cytotoxicity are still largely debated, aggregates represent a powerful
      marker to follow protein misfolding in the neurodegenerative processes. Using in
      vitro and in vivo models of mutant SOD1 associated familial ALS (fALS), we and
      other groups demonstrated that protein misfolding perturbs one of the major
      intracellular degradative pathways, the ubiquitin proteasome system, giving rise
      to a vicious cycle that leads to the further deposit of insoluble proteins and
      finally to the formation of inclusions. The aberrant response to mutated SOD1
      thus leads to the activation of the cascade of events ultimately responsible for
      cell death. Hence, our idea is that, by assisting protein folding, we might
      reduce protein aggregation, restore a fully functional proteasome activity and/or
      other cascades of events triggered by the mutant proteins responsible for motor
      neuron death in ALS. This could be obtained by stimulating mutant protein
      turnover, using an alternative degradative pathway that could clear mutant SOD1,
      namely autophagy.

PMID- 20699641
TI  - New insights into the mitochondrial nitric oxide production pathways.
AB  - Considerable evidence has appeared over the past few years that nitric oxide (NO)
      is an important anoxic metabolite and a potent signal molecule in plants. Several
      pathways operative in different cell compartments, lead to NO production.
      Mitochondria, being a major NO producing compartment, can generate it by either
      nitrite reduction occurring at nearly anoxic conditions or by the oxidative route
      via nitric oxide synthase (NOS). Recently we compared both pathways by ozone
      collision chemiluminescence and by DAF fluorescence. We found that nitrite
      reduction to NO is associated with the mitochondrial membrane fraction but not
      with the matrix. In case of the nitric oxide synthase pathway, an L-arginine
      dependent fluorescence was detected but its response to NOS inhibitors and
      substrates was untypical. Therefore the existence of NOS or NOS-like activity in
      barley root mitochondria is very doubtful. We also found that mitochondria
      scavenge NO. In addition, we found indirect evidence that mitochondria are able
      to convert NO to gaseous intermediates like NO2, N2O and N2O3.

PMID- 20699642
TI  - Regulation of the PML tumor suppressor in drug-induced senescence of human normal
      and cancer cells by JAK/STAT-mediated signaling.
AB  - The Promyelocytic leukemia protein (PML) tumor suppressor is upregulated in
      several forms of cellular senescence, however the mechanism of its induction is
      elusive. Here we show that genotoxic drugs that induce senescence, such as 5
      bromo-2'deoxyuridine (BrdU), thymidine (TMD), distamycin A (DMA), aphidicolin
      (APH), etoposide (ET) and camptothecin (CPT) all evoke expansion of PML nuclear
      compartment and its association with persistent DNA lesions in several human
      cancer cell lines and normal diploid fibroblasts. This phenomenon was accompanied
      by elevation of PML transcripts after treatment with BrdU, TMD, DMA and CPT.
      Chemical inhibition of all JAK kinases and RNAi-mediated knock-down of JAK1
      suppressed PML expression, implicating JAK/STAT-mediated signaling in regulation
      of the PML gene. As PML protein stability remained unchanged after drug
      treatment, decreased protein turnover was unlikely to explain the senescence
      associated increased abundance of PML. Furthermore, binding activity of
      Interferon Stimulated Response Element (ISRE) within the PML gene promoter, and
      suppression of reporter gene activity after deletion of ISRE from the PML
      promoter region suggested that drug-induced PML transcription is controlled via
      transcription factors interacting with this element. Collectively, our data show
      that upregulation of the PML tumor suppressor in cellular senescence triggered by
      diverse drugs including clinically used anti-cancer chemotherapeutics relies on
      stimulation of PML transcription by JAK/STAT-mediated signaling, possibly evoked
      by the autocrine/paracrine activities of senescence-associated cytokines.

PMID- 20699643
TI  - Partial ablation of adult Drosophila insulin-producing neurons modulates glucose
      homeostasis and extends life span without insulin resistance.
AB  - In Drosophila melanogaster (D. melanogaster), neurosecretory insulin-like peptide
      producing cells (IPCs), analogous to mammalian pancreatic beta cells are involved
      in glucose homeostasis. Extending those findings, we have developed in the adult
      fly an oral glucose tolerance test and demonstrated that IPCs indeed are
      responsible for executing an acute glucose clearance response. To further develop
      D. melanogaster as a relevant system for studying age-associated metabolic
      disorders, we set out to determine the impact of adult-specific partial ablation
      of IPCs (IPC knockdown) on insulin-like peptide (ILP) action, metabolic outcomes
      and longevity. Interestingly, while IPC knockdown flies are hyperglycemic and
      glucose intolerant, these flies remain insulin sensitive as measured by
      peripheral glucose disposal upon insulin injection and serine phosphorylation of
      a key insulin-signaling molecule, Akt. Significant increases in stored glycogen
      and triglyceride levels as well as an elevated level of circulating lipid
      measured in adult IPC knockdown flies suggest profound modulation in energy
      metabolism. Additional physiological outcomes measured in those flies include
      increased resistance to starvation and impaired female fecundity. Finally,
      increased life span and decreased mortality rates measured in IPC knockdown flies
      demonstrate that it is possible to modulate ILP action in adult flies to achieve
      life span extension without insulin resistance. Taken together, we have
      established and validated an invertebrate genetic system to further investigate
      insulin action, metabolic homeostasis and regulation of aging regulated by adult
      IPCs.

PMID- 20699644
TI  - Splice-variant changes of the Ca(V)3.2 T-type calcium channel mediate voltage
      dependent facilitation and associate with cardiac hypertrophy and development.
AB  - Low voltage-activated T-type calcium (Ca) channels contribute to the normal
      development of the heart and are also implicated in pathophysiological states
      such as cardiac hypertrophy. Functionally distinct T-type Ca channel isoforms can
      be generated by alternative splicing from each of three different T-type genes
      (Ca(V)3.1, Ca(V)3.2,Ca(V)3.3), although it remains to be described whether
      specific splice variants are associated with developmental states and
      pathological conditions. We aimed to identify and functionally characterize
      Ca(V)3.2 T-type Ca channel alternatively spliced variants from newborn animals
      and to compare with adult normotensive and spontaneously hypertensive rats (SHR).
      DNA sequence analysis of full-length Ca(V)3.2 cDNA generated from newborn heart
      tissue identified ten major regions of alternative splicing, the more common
      variants of which were analyzed by quantitative real-time PCR (qRT-PCR) and also
      subject to functional examination by whole-cell patch clamp. The main findings
      are that: (1) cardiac Ca(V)3.2 T-type Ca channels are subject to considerable
      alternative splicing, (2) there is preferential expression of Ca(V)3.2(-25)
      splice variant channels in newborn rat heart with a developmental shift in adult
      heart that results in approximately equal levels of expression of both (+25) and
      (-25) exon variants, (3) in the adult stage of hypertensive rats there is a both
      an increase in overall Ca(V)3.2 expression and a shift towards expression of
      Ca(V)3.2(+25) containing channels as the predominant form, and (4) alternative
      splicing confers a variant-specific voltage-dependent facilitation of Ca(V)3.2
      channels. We conclude that Ca(V)3.2 alternative splicing generates significant T
      type Ca channel structural and functional diversity with potential implications
      relevant to cardiac developmental and pathophysiological states.

PMID- 20699645
TI  - M(a)TCH-ing up mitochondrial apoptosis.

PMID- 20699647
TI  - Low abundance does not mean less importance in cysteine metabolism.
AB  - The cysteine molecule plays an essential role in cells because it is part of
      proteins and because it functions as a reduced sulfur donor molecule. In
      addition, the cysteine molecule may also play a role in the redox signaling of
      different stress processes. Even though the synthesis of cysteine by the most
      abundant of the isoforms of O-acetylserine(thiol)lyase in the chloroplast, the
      mitochondria and the cytosol is relatively well-understood, the role of the other
      less common isoforms homologous to O-acetylserine(thiol)lyase is unknown. Several
      studies on two of these isoforms, one located in the cytosol and the other one in
      the chloroplast, have shown that while one isoform operates with a desulfhydrase
      activity and is essential to regulate the homeostasis of cysteine in the cytosol,
      the other, located in the chloroplast, synthesizes S-sulfocysteine. This
      metabolite appears to be essential for the redox regulation of the chloroplast
      under certain lighting conditions.

PMID- 20699646
TI  - Roles for Gcn5 in promoting nucleosome assembly and maintaining genome integrity.
AB  - The process of coordinated DNA replication and nucleosome assembly, termed
      replication-coupled (RC) nucleosome assembly, is important for the maintenance of
      genome integrity. Loss of genome integrity is linked to aging and cancer. RC
      nucleosome assembly involves deposition of histone H3-H4 by the histone
      chaperones CAF-1, Rtt106 and Asf1 onto newly-replicated DNA. Coordinated actions
      of these three histone chaperones are regulated by modifications on the histone
      proteins. One such modification is histone H3 lysine 56 acetylation (H3K56Ac), a
      mark of newly-synthesized histone H3 that regulates the interaction between H3-H4
      and the histone chaperones CAF-1 and Rtt106 following DNA replication and DNA
      repair. Recently, we have shown that the lysine acetyltransferase Gcn5 and H3 N
      terminal tail lysine acetylation also regulates the interaction between H3-H4 and
      CAF-1 to promote the deposition of newly-synthesized histones. Genetic studies
      indicate that Gcn5 and Rtt109, the H3K56Ac lysine acetyltransferase, function in
      parallel to maintain genome stability. Utilizing synthetic genetic array
      analysis, we set out to identify additional genes that function in parallel with
      Gcn5 in response to DNA damage. We summarize here the role of Gcn5 in nucleosome
      assembly and suggest that Gcn5 impacts genome integrity via multiple mechanisms,
      including nucleosome assembly.

PMID- 20699648
TI  - Lysyl tRNA synthetase is required for the translocation of calreticulin to the
      cell surface in immunogenic death.
AB  - In response to immunogenic cell death inducers, calreticulin (CRT) translocates
      from its orthotopic localization in the lumen of the endoplasmic reticulum (ER)
      to the surface of the plasma membrane where it serves as an engulfment signal for
      antigen-presenting cells.(1) Here, we report that yet another ER protein, the
      lysyl-tRNA synthetase (KARS), was exposed on the surface of stressed cells, on
      which KARS co-localized with CRT in lipid rafts. Depletion of KARS with small
      interfering RNAs suppressed CRT exposure induced by anthracyclines or UVC light.
      In contrast to CRT, KARS was also found in the supernatant of stressed cells.
      Recombinant KARS protein was unable to influence the binding of recombinant CRT
      to the cell surface. Moreover, recombinant KARS protein was unable to stimulate
      macrophages in vitro. These results underscore the contribution of KARS to the
      emission of (one of) the principal signal(s) of immunogenic cell death, CRT
      exposure.

PMID- 20699649
TI  - Targeting K(V) channels rescues retinal ganglion cells in vivo directly and by
      reducing inflammation.
AB  - Retinal ganglion cell (RGC) degeneration is an important cause of visual
      impairment, and results in part from microglia-mediated inflammation. Numerous
      experimental studies have focused on identifying drug targets to rescue these
      neurons. We recently showed that K(V)1.1 and K(V)1.3 channels are expressed in
      adult rat RGCs and that siRNA-mediated knockdown of either channel reduces RGC
      death after optic nerve transection. Earlier we found that K(V)1.3 channels also
      contribute to microglial activation and neurotoxicity; raising the possibility
      that these channels contribute to neurodegeneration through direct roles in RGCs
      and through inflammatory mechanisms. Here, RGC survival was increased by combined
      siRNA-mediated knockdown of K(V)1.1 and K(V)1.3 in RGCs, but survival was much
      greater when knockdown of either channel was combined with intraocular injection
      of a K(V)1.3 channel blocker (agitoxin-2 or margatoxin). After axotomy, increased
      expression of several inflammation-related molecules preceded RGC loss and,
      consistent with a dual mechanism, their expression was differentially affected
      when channel knockdown in RGCs was combined with K(V)1.3 blocker injection.
      K(V)1.3 blockers reduced activation of retinal microglia and their tight
      apposition along RGC axon fascicles after axotomy, but did not prevent their
      migration from the inner plexiform to the damaged ganglion cell layer. Expression
      of several growth factors increased after axotomy; and again, there were
      differences following blocker injection compared with RGC-selective channel
      knockdown. These results provide evidence that K(V)1.3 channels play important
      roles in apoptotic degeneration of adult RGCs through cell-autonomous mechanisms
      mediated by channels in the neurons, and nonautonomous mechanisms mediated by
      microglia and inflammation.

PMID- 20699650
TI  - The role of STEP in Alzheimer's disease.
AB  - Amyloid beta (Abeta), the putative causative agent in Alzheimer's disease, is
      known to affect glutamate receptor trafficking. Previous studies have shown that
      Abeta downregulates the surface expression of N-methyl D-aspartate type glutamate
      receptors (NMDARs) by the activation of STriatal-Enriched protein tyrosine
      Phosphatase 61 (STEP61). More recent findings confirm that STEP61 plays an
      important role in Abeta-induced NMDAR endocytosis. STEP levels are elevated in
      human AD prefrontal cortex and in the cortex of several AD mouse models. The
      increase in STEP61 levels and activity contribute to the removal of GluN1/GluN2B
      receptor complexes from the neuronal surface membranes. The elevation of STEP61
      is due to disruption in the normal degradation of STEP61 by the ubiquitin
      proteasome system. Here, we briefly discuss additional studies in support of our
      hypothesis that STEP61 contributes to aspects of the pathophysiology in
      Alzheimer's disease. Exogenous application of Abeta-enriched conditioned medium
      (7PA2-CM) to wild-type cortical cultures results in a loss of GluN1/GluN2B
      subunits from neuronal membranes. Abeta-mediated NMDAR internalization does not
      occur in STEP knock-out cultures, but is rescued by the addition of active TAT
      STEP to the cultures prior to Abeta treatment.

PMID- 20699651
TI  - Induced root-secreted phenolic compounds as a belowground plant defense.
AB  - Rhizosphere is the complex place of numerous interactions between plant roots,
      microbes and soil fauna. Whereas plant interactions with aboveground organisms
      are largely described, unravelling plant belowground interactions remains
      challenging. Plant root chemical communication can lead to positive interactions
      with nodulating bacteria, mycorriza or biocontrol agents or to negative
      interactions with pathogens or root herbivores. A recent study suggested that
      root exudates contribute to plant pathogen resistance via secretion of
      antimicrobial compounds. These findings point to the importance of plant root
      exudates as belowground signalling molecules, particularly in defence responses.
      In our report, we showed that under Fusarium attack the barley root system
      launched secretion of phenolic compounds with antimicrobial activity. The
      secretion of de novo biosynthesized t-cinnamic acid induced within 2 days
      illustrates the dynamic of plant defense mechanisms at the root level. We discuss
      the costs and benefits of induced defense responses in the rhizosphere. We
      suggest that plant defence through root exudation may be cultivar dependent and
      higher in wild or less domesticated varieties.

PMID- 20699652
TI  - Reversibility of pre-malignant estrogen-induced epigenetic changes.
AB  - The development of early detection and prevention strategies of breast cancer
      relies on defining molecular and cellular events that characterize progressive
      alterations underlying preneoplastic changes in the mammary epithelium. Studies
      have shown that estrogen exerts its carcinogenic effects through both genetic and
      epigenetic pathways to promote imbalances in proliferation and apoptosis, genomic
      instability and cancer. The purpose of this study was to identify the earliest
      epigenetic changes that could be detected in response to estrogen treatment. More
      importantly, having detected these early pre-malignant epigenetic changes, a
      follow-up study was designed to address the potential to reverse these estrogen
      induced alterations. Using a well-established ACI rat model, morphological and
      epigenetic changes were identified in the mammary gland tissue as early as 2 days
      after exposure to constitutively elevated estrogen levels produced by continuous
      release estrogen mini-pellets. Progressive hyperproliferative changes were
      paralleled by epigenetic disturbances, including the upregulation of DNA
      methyltransferases and hyperacetylation of histone residues. These changes could
      be detected early, and they continued to persist if estrogen was maintained
      within a high physiological range. Epigenetic features of short-term estrogen
      exposure were strikingly similar to hallmarks of cancer promotion and
      progression. Yet, importantly, these changes exhibited a degree of reversibility
      if a source of elevated levels of estrogen was removed. Knowing that operational
      reversibility during the promotion stage of carcinogenesis provides a window for
      intervention, the potential to reverse the effects of elevated levels of estrogen
      prior to tumor development may prove to be a promising avenue to explore.

PMID- 20699654
TI  - microRNA deficiency in pancreatic islet cells exacerbates streptozotocin-induced
      murine autoimmune diabetes.
AB  - Recent studies have demonstrated that gene expression is regulated not only by
      protein-coding genes, but also by nonprotein-coding small RNA molecules,
      microRNAs (miRNAs). miRNAs have emerged as important regulators involved in many
      biological processes, including cell proliferation and differentiation, apoptosis
      and metabolism and disease development. Here we report that specific miRNA
      deficiency in pancreatic islet cells exacerbates multiple low-dose streptozotocin
      induced murine autoimmune type 1 diabetes, suggesting that miRNAs expressed in
      islet beta cells regulate their susceptibility to immune-mediated beta cell
      destruction.

PMID- 20699653
TI  - Analysis of steroid hormone effects on xenografted human NF1 tumor schwann cells.
AB  - The neurofibroma, a common feature of neurofibromatosis type 1 (NF1), is a benign
      peripheral nerve sheath tumor that contains predominantly Schwann cells (SC).
      There are reports that neurofibroma growth may be affected by hormonal changes,
      particularly in puberty and pregnancy, suggesting an influence by steroid
      hormones. This study examined the effects of estrogen and progesterone on
      proliferation and apoptosis in a panel of NF1 tumor xenografts. SC-enriched
      cultures derived from three human NF1 tumor types (dermal neurofibroma, plexiform
      neurofibroma, and malignant peripheral nerve sheath tumor (MPNST)) were
      xenografted in sciatic nerves of ovariectomized scid /Nf1-/+ mice. At the same
      time, mice were implanted with time-release pellets for systemic delivery of
      progesterone, estrogen or placebo. Proliferation and apoptosis by the xenografted
      SC were examined two months after implantation, by Ki67 immunolabeling and TUNEL.
      Estrogen was found to increase the growth of all three MPNST xenografts.
      Progesterone was associated with increased growth in two of the three MPNSTs, yet
      decreased growth of the other. Of the four dermal neurofibroma xenografts tested,
      estrogen caused a statistically significant growth increase in one, and
      progesterone did in another. Of the four plexiform neurofibroma SC xenografts,
      estrogen and progesterone significantly decreased growth in one of the
      xenografts, but not the other three. No relationship of patient age or gender to
      steroid response was observed. These findings indicate that human NF1 Schwann
      cells derived from some tumors show increased proliferation or decreased
      apoptosis in response to particular steroid hormones in a mouse xenograft model.
      This suggests that anti-estrogen or anti-progesterone therapies may be worth
      considering for specific NF1 neurofibromas and MPNSTs.

PMID- 20699655
TI  - Why cyclin Y? A highly conserved cyclin with essential functions.
AB  - Cyclin Y is one of the most highly conserved members of the cyclin superfamily of
      proteins, which are famous for their crucial roles in regulating the cell cycle
      and transcription. Despite this high degree of conservation, very little was
      known about Cyclin Y function prior to a handful of studies published in this
      past year. Cyclins typically function by activating cyclin-dependent kinases
      (Cdks) and one insight has come from the identification of a Cdk that is
      activated by Cyclin Y. Yeast two-hybrid data first linked Cyclin Y with Cdk14,
      known as Eip63E in Drosophila or PFTAIRE1 in vertebrates. In Drosophila, both
      Cyclin Y and Eip63E are essential at many stages of development, from
      embryogenesis to metamorphosis and null mutants show a similar spectrum of
      developmental defects. In cultured cells, Cyclin Y and Eip63E were shown to
      phosphorylate the Wg/Wnt co-receptor Arrow/LRP6 in a ligand-independent manner.
      Eip63E is recruited to LRP6 at the plasma membrane by interacting with Cyclin Y,
      which is tethered to the membrane through an N-terminal myristoylation. Cyclin Y
      dependent LRP6 phosphorylation appears to prime the receptor for subsequent
      ligand-dependent phosphorylation and activation of the canonical Wnt signaling
      pathway. Interestingly, Wnt receptor phosphorylation and signaling is maximal in
      G2/M when Cyclin Y is at its highest levels, suggesting that Cyclin Y may serve
      to entrain Wnt signaling to the cell cycle. Given the wide range of roles for Wnt
      signaling during development, these studies may help explain why Cyclin Y is
      required at several developmental stages and in turn why these proteins are so
      well conserved in metazoans.

PMID- 20699656
TI  - Establishing positional information through gradient dynamics: a lesson from the
      Hedgehog signaling pathway.
AB  - A long standing question in developmental biology is how morphogen gradients
      establish positional information during development. Although the existence of
      gradients and their role in developmental patterning is no longer in doubt, the
      ability of cells to respond to different morphogen concentrations has been
      controversial. In the Drosophila wing disc, Hedgehog (Hh) forms a concentration
      gradient along the anterior-posterior axis and establishes at least three
      different gene expression patterns. In a recent study, we challenged the
      prevailing idea that Hh establishes positional information in a dose-dependent
      manner and proposed a model in which dynamics of the gradient, resulting from the
      Hh gene network architecture, determines pattern formation in the wing disc. In
      this Extra View, we discuss further the methodology used in this study, highlight
      differences between this and other models of developmental patterning, and also
      present some questions that remain to be answered in this system.

PMID- 20699657
TI  - Cold-responsive gene regulation during cold acclimation in plants.
AB  - Regulation of the transcriptome is necessary for plants to acquire cold
      tolerance, and cold induces several genes via a cold signaling pathway. The
      transcription factors CBF/DREB1 (C-repeat binding factor/dehydration responsive
      element binding1) and ICE1 (inducer of CBF expression1) have important roles in
      the regulation of cold-responsive gene expression. ICE1 is post-translationally
      regulated by ubiquitylation-mediated proteolysis and sumoylation. This mini
      review highlights some recent studies on plant cold signaling. The relationships
      among cold signaling, salicylic acid accumulation and stomatal development are
      also discussed.

PMID- 20699658
TI  - 15-Hydroxyprostaglandin dehydrogenase is a tumor suppressor of human gastric
      cancer.
AB  - Cyclooxygenase-2 (COX-2), the key enzyme in prostaglandin synthesis, is often
      over-expressed in human gastric cancer. Recently, 15-hydroxyprostaglandin
      dehydrogenase [NAD+] (15-PGDH), the key enzyme in prostaglandin degradation, was
      found to be down-regulated in human gastric cancer tissues, but little is known
      about its role in gastric tumorigenesis. In this study, expression plasmids
      containing 15-PGDH siRNA were constructed and transfected into the gastric cancer
      cell line MKN45, which expresses endogenous 15-PGDH at a high level. The 15-PGDH
      gene was also transfected into the gastric cancer cell line SGC7901, which
      expresses endogenous 15-PGDH at a low level. When compared with the empty vector
      transfectant, MKN45 cells stably transfected with the 15-PGDH siRNA plasmid had a
      significantly increased proliferation rate. In contrast, SGC7901 cells stably
      transfected with the 15-PGDH cDNA had a significantly decreased growth rate.
      Furthermore, increased expression of 15-PGDH suppressed clone formation of
      gastric cancer cells in plate and soft agar colony formation assays in vitro and
      suppressed tumor formation in athymic nude mice in vivo. Stable silencing of 15
      PGDH in gastric cancer cells also enhanced cell cycle entry in vitro. These
      results demonstrate for the first time that 15-PGDH acts as a tumor suppressor in
      human gastric cancer and provide further validation for 15-PGDH as a potential
      therapeutic target for human gastric cancer.

PMID- 20699660
TI  - Fine-tuning CD8(+) T cell functional responses: mTOR acts as a rheostat for
      regulating CD8(+) T cell proliferation, survival and differentiation?
AB  - Naive CD8(+) T cells are instructed by antigen, co-stimulatory molecules and
      cytokines to undergo proliferation, clonal expansion and differentiation for
      effector and memory functions. The integration of extracellular instructions
      induces coordinated signaling cascades and transcriptional programs to determine
      CD8(+) T cell functional fate. Although, an important role for the energy
      sensitive kinase-mammalian target of rapamycin (mTOR) in regulating T cell
      proliferation and cell survival instep with cellular metabolic status has been
      demonstrated, emerging information indicates that mTOR also acts as a critical
      regulator of effector and memory functional fates in CD8(+) T cells. Herein, we
      discuss the pathways by which cellular metabolism regulates proliferation,
      survival and functional differentiation of CD8(+) T cells and focus on the role
      of mTOR as the rheostat that strikes a balance between effector and memory
      differentiation of CD8(+) T cells for enabling adaptive host immunity.

PMID- 20699659
TI  - Random mutagenesis screening indicates the absence of a separate H(+)-sensor in
      the pH-sensitive Kir channels.
AB  - Several inwardly-rectifying (Kir) potassium channels (Kir1.1, Kir4.1 and Kir4.2)
      are characterised by their sensitivity to inhibition by intracellular H(+) within
      the physiological range. The mechanism by which these channels are regulated by
      intracellular pH has been the subject of intense scrutiny for over a decade, yet
      the molecular identity of the titratable pH-sensor remains elusive. In this study
      we have taken advantage of the acidic intracellular environment of S. cerevisiae
      and used a K(+) -auxotrophic strain to screen for mutants of Kir1.1 with impaired
      pH-sensitivity. In addition to the previously identified K80M mutation, this
      unbiased screening approach identified a novel mutation (S172T) in the second
      transmembrane domain (TM2) that also produces a marked reduction in pH
      sensitivity through destabilization of the closed-state. However, despite this
      extensive mutagenic approach, no mutations could be identified which removed
      channel pH-sensitivity or which were likely to act as a separate H(+) -sensor
      unique to the pH-sensitive Kir channels. In order to explain these results we
      propose a model in which the pH-sensing mechanism is part of an intrinsic gating
      mechanism common to all Kir channels, not just the pH-sensitive Kir channels. In
      this model, mutations which disrupt this pH-sensor would result in an increase,
      not reduction, in pH-sensitivity. This has major implications for any future
      studies of Kir channel pH-sensitivity and explains why formal identification of
      these pH-sensing residues still represents a major challenge.

PMID- 20699661
TI  - SnoN/SkiL, a TGFbeta signaling mediator: a participant in autophagy induced by
      arsenic trioxide.
AB  - Effective treatment of cancer cells with chemotherapeutic drugs relies on their
      ability to induce cell death, making the discovery of their mechanisms of action
      crucial. Arsenic trioxide (As(2)O(3)), used in the treatment of promyelocytic
      leukemia (PML), triggers cell death in several solid tumor cell lines including
      ovarian carcinomas. While As(2)O(3) is remarkably cytotoxic in human ovarian
      cancer cells, its mechanism of action is poorly understood. We recently
      investigated the effects of As(2)O(3) on several transforming growth factor-beta
      (TGFbeta) signaling mediators to better understand its cell death mechanism.
      Indeed, dysregulated (TGFbeta) signaling is typical of ovarian cancers. Based on
      our findings, we propose that As(2)O(3) induces a Beclin 1-independent autophagic
      pathway in ovarian carcinoma cells by modulating SnoN/SkiL expression,
      implicating SnoN as a novel therapeutic target for ovarian cancers.

PMID- 20699662
TI  - Nrf2: a central regulator of UV protection in the epidermis.

PMID- 20699663
TI  - How does the mammalian target of rapamycin (mTOR) influence CD8 T cell
      differentiation?
AB  - Naive T lymphocytes maintain a quiescent resting state until they encounter
      antigen whereupon they undergo a switch in their metabolic program in preparation
      for proliferation and differentiation. This activation process involves a
      dramatic upregulation of protein synthesis that is essential for cell growth and
      the differentiation of effector function. An essential regulator of protein
      synthesis in T cells is the mammalian target of rapamycin (mTOR), a
      serine/threonine kinase that regulates both the availability of amino acids and
      the process of cap-dependent translation. Recent data indicate that mTOR
      influences activation and cell fate determination in T cells. We discuss these
      findings in light of what is currently known about the function of mTOR and its
      targets in CD8 T cells.

PMID- 20699664
TI  - Calcitriol enhances gemcitabine anti-tumor activity in vitro and in vivo by
      promoting apoptosis in a human pancreatic carcinoma model system.
AB  - Gemcitabine is the standard care chemotherapeutic agent to treat pancreatic
      cancer. Previously we demonstrated that calcitriol (1, 25
      dihydroxycholecalciferol) has significant anti-proliferative effects in vitro and
      in vivo in multiple tumor models and enhances the activity of a variety of
      chemotherapeutic agents. We therefore investigated whether calcitriol could
      potentiate the cytotoxic activity of gemcitabine in the human pancreatic cancer
      Capan-1 model system. Isobologram analysis revealed that calcitriol and
      gemcitabine had synergistic antiproliferative effect over a wide range of drug
      concentrations. Calcitriol did not reduce the cytidine deaminase activity in
      Capan-1 tumors nor in the livers of Capan-1 tumor bearing mice. Calcitriol and
      gemcitabine combination promoted apoptosis in Capan-1 cells compared with either
      agent alone. The combination treatment also increased the activation of caspases
      8, -9, -6 and -3 in Capan-1 cells. This result was confirmed by substrate-based
      caspase activity assay. Akt phosphorylation was reduced by calcitriol and
      gemcitabine combination treatment compared to single agent treatment. However,
      ERK1/2 phosphorylation was not modulated by either agent alone or by the
      combination. Tumor regrowth delay studies showed that calcitriol in combination
      with gemcitabine resulted in a significant reduction of Capan-1 tumor volume
      compared to single agent treatment. Our study suggests that calcitriol and
      gemcitabine in combination promotes caspase-dependent apoptosis, which may
      contribute to increased anti-tumor activity compared to either agent alone.

PMID- 20699665
TI  - A role of plakophilins in the regulation of translation.
AB  - Plakophilins 1-3 are members of the p120(ctn)-family of armadillo related
      proteins. They have been characterized as desmosomal plaque proteins, stabilizing
      desmosomal cadherins at the plasma membrane and interacting with the cytoskeletal
      linker protein desmoplakin. Loss of cell adhesion contributes to cancerogenesis.
      In agreement with this, some tumors were found to lack plakophilin expression.
      Surprisingly, in other tumors, plakophilins 1 and 3 are overexpressed. We have
      recently identified a function of plakophilins 1 and 3 in the regulation of
      protein synthesis. Plakophilin 1 was characterized as a component of the cap
      binding translation initiation complex where it associates directly with the
      initiation factor eIF4A1. Plakophilin 1 not only stimulated the recruitment of
      eIF4A1 into the cap complex but also its helicase activity. This pointed to a
      role of plakophilin 1 in the stimulation of proliferation. Given the importance
      of mRNA translation and protein synthesis in the development of cancer, we
      speculate that overexpressed plakophilin 1 could contribute to tumor formation.
      Thus, plakophilin's function in cancerogenesis could go both ways: while an
      increase of plakophilin could support cancerogenesis via the stimulation of
      translation and proliferation, loss of plakophilin could contribute to
      cancerogenesis and/or metastasis via loss of contact inhibition and increased
      motility. Elucidating the regulation of plakophilin's function in adhesion versus
      translation will help to understand this context-dependent phenomenon.

PMID- 20699666
TI  - Mitotic Golgi vesiculation involves mechanisms independent of Ser25
      phosphorylation of GM130.
AB  - During mitosis, the Golgi undergoes two sequential fragmentation steps to break
      from ribbon to individual stacks, then from stacks to vesicles. While the
      mechanism that regulates the first step has been studied, it remains obscure how
      the second vesiculation step is regulated. It has been suggested that Cdk1
      dependent phosphorylation of the cis-Golgi matrix protein GM130 regulates the
      second step. Here we have tested if phorphorylation of GM130 by Cdk1 is required
      for Golgi vesiculation and mitotic progression. Inhibition of Cdk1 activity
      caused a failure of Golgi vesiculation and defects in chromosome
      congression/segregation. Expression of non-phosphorylatable mutant of GM130
      (GM130S25A) in cells depleted of endogenous GM130 caused no apparent defects in
      Golgi vesiculation and mitotic progression. Similarly, no apparent defects in
      Golgi vesiculation and mitotic progression were observed when GM130S25A was
      expressed in GM130-deficient CHO cells. Our observations suggest that while Cdk1
      based phosphorylation is essential for mitotic Golgi vesiculation, mammalian
      cells could possess redundant, S25 phosphorylation of GM130 independent pathways
      that ensure Golgi vesiculation and mitotic progression.

PMID- 20699667
TI  - Induction of autophagy by dual mTORC1-mTORC2 inhibition in BCR-ABL-expressing
      leukemic cells.
AB  - In recent years, there have been substantial research advances on the mechanisms
      by which BCR-ABL transforms hematopoietic cells and promotes leukemic cell growth
      and survival. Among the diverse signaling cascades activated by BCR-ABL, the mTOR
      pathway plays a critical role in mRNA translation of genes that promote
      leukemogenesis and mitogenic responses. We have recently shown that dual
      targeting of mTORC1 and mTORC2 complexes using a catalytic mTOR inhibitor, OSI
      027, results in generation of potent antileukemic effects against BCR-ABL
      transformed cells. Such effects were also seen in cells expressing the T315I
      mutation, which is resistant to all currently approved BCR-ABL kinase inhibitors.
      Our studies also demonstrate that such dual catalytic inhibition of mTORC2 and
      mTORC1 complexes in BCR-ABL-expressing K562 cells results in induction of
      autophagy, and that inhibition of the autophagic process using chloroquine
      promotes apoptosis of these cells. Altogether, our studies suggest that autophagy
      may be a limiting factor for the induction of apoptosis during dual mTORC2-mTORC1
      targeting, in at least some types of BCR-ABL-expressing cells and have raised the
      potential of combinations of catalytic inhibitors of mTOR with autophagy
      inhibitors for the treatment of refractory Ph(+) leukemias.

PMID- 20699668
TI  - Senescence is heterogeneous in mesenchymal stromal cells: kaleidoscopes for
      cellular aging.

PMID- 20699669
TI  - Integrative computed tomographic imaging of cardiac structure, function,
      perfusion, and viability.
AB  - Recent advances in multidetector-row computed tomography (MDCT) technology have
      created new opportunities in cardiac imaging and provided new insights into a
      variety of disease states. Use of 64-slice coronary computed tomography
      angiography has been validated for the evaluation of clinically relevant coronary
      artery stenosis with high negative predictive values for ruling out significant
      obstructive disease. This technology has also advanced the care of patients with
      acute chest pain by simultaneous assessment of acute coronary syndrome, pulmonary
      embolism, and acute aortic syndrome ("triple rule out"). Although MDCT has been
      instrumental in the advancement of cardiac imaging, there are still limitations
      in patients with high or irregular heart rates. Newer MDCT scanner generations
      hold promise to improve some of these limitations for noninvasive cardiac
      imaging. The evaluation of coronary artery stenosis remains the primary clinical
      indication for cardiac computed tomography angiography. However, the use of MDCT
      for simultaneous assessment of coronary artery stenosis, atherosclerotic plaque
      formation, ventricular function, myocardial perfusion, and viability with a
      single modality is under intense investigation. Recent technical developments
      hold promise for accomplishing this goal and establishing MDCT as a comprehensive
      stand-alone test for integrative imaging of coronary heart disease.

PMID- 20699670
TI  - A novel approach to left atrial appendage exclusion: the WATCHMAN device.
AB  - Atrial fibrillation (AF), a very common cardiac arrhythmia, is a well-recognized
      predisposing factor for embolic stroke. While warfarin remains the cornerstone of
      anticoagulant treatment in patients with AF, it is often underutilized because of
      increased bleeding complications and frequent monitoring requirements. It has
      been documented that the left atrial appendage (LAA) is the main source of left
      atrial thrombus that causes strokes in AF patients. Thus, closure of the LAA may
      be an effective strategy in stroke reduction. Several devices have been used in
      closure of the LAA. The WATCHMAN device appears to be a safe and efficacious
      device for closure of the LAA as recently demonstrated in the PROTECT AF trial.

PMID- 20699671
TI  - Management of acute complicated and uncomplicated type B dissection of the aorta:
      focus on endovascular stent grafting.
AB  - Endovascular repair of aortic dissection is the subject of multiple studies. This
      article aims to review the current literature on Type B complicated and
      uncomplicated dissection, including indications for medical therapy, open
      surgical therapy, and endovascular therapy. The review suggests a benefit for
      thoracic endovascular aortic repair in complicated dissection and medical therapy
      for uncomplicated dissection. Upcoming trials may shed more light on this issue.

PMID- 20699673
TI  - Testosterone and coronary artery disease.
AB  - Cardiovascular disease remains the leading cause of death in most of the
      developed world despite advances in both prevention and treatment. At the same
      time, the incidence rates of cardiovascular disease differ greatly between the
      genders, with men more likely than women to manifest ischemic heart disease. This
      observation has prompted new research initiatives to explain the discrepancy in
      heart disease prevalence and incidence between the sexes. Whether androgens
      affect cardiovascular disease adversely remains a contentious issue, with some
      data pointing to a deleterious effect of androgens on lipid profiles, and other
      studies revealing androgens' possible benefits on cardiovascular function. This
      review will examine the relationship between the endogenous production of
      androgen as well as the exogenous replacement of testosterone in men and the
      possible links to cardiovascular disease. The role of testosterone in male
      cardiovascular health is not completely understood, and additional studies are
      needed to explain its effect on atherosclerosis and its complications.

PMID- 20699672
TI  - Treatment of anemia in heart failure: potential risks and benefits of intravenous
      iron therapy in cardiovascular disease.
AB  - Iron-deficiency anemia is common in patients with heart failure (HF), but the
      optimum diagnostic tests to detect iron deficiency and the treatment options to
      replete iron have not been fully characterized. Recent studies in patients with
      HF indicate that intravenous iron can rapidly replenish iron stores in patients
      having iron-deficiency anemia, with resultant increased hemoglobin levels and
      improved functional capacity. Preliminary data from a subgroup analysis also
      suggest that supplemental intravenous iron therapy can improve functional
      capacity even in those subjects without anemia. The mechanisms responsible for
      this observation are not fully characterized, but may be related to beneficial
      effects of iron supplementation on mitochondrial respiration in skeletal muscle.
      The long-term safety of using intravenous iron supplementation in HF populations
      is not known. Iron is a known pro-oxidant factor that can inhibit nitric oxide
      signaling and irreversibly injury cells. Increased iron stores are associated
      with vascular endothelial dysfunction and increased risk of coronary heart
      disease events. Additional clinical trials are needed to more fully characterize
      the therapeutic potential and safety of intravenous iron in HF patients.

PMID- 20699675
TI  - Pitavastatin: a new HMG-CoA reductase inhibitor for the treatment of
      hypercholesterolemia.
AB  - Because of their good tolerability and their positive effect on lipid parameters
      and clinical outcomes, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors
      (statins) have become the drugs of first choice for the management of
      dyslipidemia. Pitavastatin is the newest member in the statin family and received
      Food and Drug Administration approval for oral use in August 2009. Compared to
      other statins such as atorvastatin, simvastatin and pravastatin at specific
      doses, pitavastatin dosed at 1 to 4 mg daily showed similar efficacy in lowering
      low-density lipoprotein cholesterol (LDL-C) and altering other lipid parameters
      according to a number of studies. In addition, pitavastatin demonstrated
      cholesterol-lowering efficacy in special populations such as the elderly,
      patients with diabetes, and patients with higher cardiovascular risk. Because
      pitavastatin is minimally metabolized by the cytochrome P-450 isoenzymes, it is
      associated with a lower frequency of drug-drug interactions, and this may be a
      desirable characteristic of pitavastatin. Beneficial effects, such as reductions
      of coronary plaque volume and fibrofatty composition, have also been observed
      with pitavastatin. Thus far, the safety profile of pitavastatin is favorable and
      appears to be similar to those of other statins. Given its encouraging
      pharmacokinetic and pharmacodynamic characteristics, pitavastatin is likely to be
      a good alternative to other more established statins. The pharmacologic and
      pharmacokinetic properties of pitavastatin are reviewed in this article.

PMID- 20699678
TI  - Infectious disease (in) epidemiology.

PMID- 20699679
TI  - Genetics in epidemiology.

PMID- 20699674
TI  - Fish oil for the treatment of cardiovascular disease.
AB  - Omega-3 fatty acids, which are found abundantly in fish oil, are increasingly
      being used in the management of cardiovascular disease. It is clear that fish
      oil, in clinically used doses (typically 4 g/d of eicosapentaenoic acid and
      docosahexaenoic acid) reduce high triglycerides. However, the role of omega-3
      fatty acids in reducing mortality, sudden death, arrhythmias, myocardial
      infarction, and heart failure has not yet been established. This review will
      focus on the current clinical uses of fish oil and provide an update on their
      effects on triglycerides, coronary artery disease, heart failure, and arrhythmia.
      We will explore the dietary sources of fish oil as compared with drug therapy,
      and discuss the use of fish oil products in combination with other commonly used
      lipid-lowering agents. We will examine the underlying mechanism of fish oil's
      action on triglyceride reduction, plaque stability, and effect in diabetes, and
      review the newly discovered anti-inflammatory effects of fish oil. Finally, we
      will examine the limitations of current data and suggest recommendations for fish
      oil use.

PMID- 20699681
TI  - Lasagna plots: a saucy alternative to spaghetti plots.

PMID- 20699682
TI  - HIV incidence estimation using the BED capture enzyme immunoassay: systematic
      review and sensitivity analysis.
AB  - BACKGROUND: HIV incidence estimates are essential for understanding the evolution
      of the HIV epidemic and the impact of interventions. Tests for recent HIV
      infection allow incidence estimation based on a single cross-sectional survey.
      The BED IgG-Capture Enzyme Immunoassay (BED assay) is a commercially available
      and widely used test for recent HIV infection. METHODS: In a systematic
      literature search for BED assay studies, we identified 1181 unique studies, 1138
      of which were excluded based on titles or abstracts. We conducted reviews of the
      43 remaining publications and a further 23 studies identified on conference Web
      sites or by colleagues. Thirty-nine articles were included in the final review.
      We investigated the sensitivity of incidence values to various estimation methods
      and parameter choices. RESULTS: BED assay surveys have been conducted on 5
      continents in general populations and high-risk groups, using 1 or more of 10
      distinct incidence formulae. Most studies used estimators that do not account for
      assay imperfection. Those studies that correct for assay imperfection commonly do
      not use locally valid assay parameters. Incidence estimates were very sensitive
      to methodological and parameter choices. Most confidence intervals provided good
      assessment of uncertainty due to counting error, but only a few incorporated
      parameter uncertainty. CONCLUSIONS: BED assay surveys can produce valid HIV
      incidence estimates, but many studies have not sufficiently accounted for assay
      imperfection. Future studies should (1) report all information necessary for
      incidence point and uncertainty estimation, (2) use an unbiased estimator with
      locally valid assay calibration parameters, and (3) compute confidence intervals
      that take into account parameter uncertainty.

PMID- 20699683
TI  - A conversation with John Last. Interview by Julian Little.

PMID- 20699684
TI  - Sufficient-cause interaction.

PMID- 20699685
TI  - Diabetes mellitus in rural India.

PMID- 20699687
TI  - 10th International Conference on Health Effects of Incorporated Radionuclides.

PMID- 20699688
TI  - Life-span study on late effects of 224Ra in children and adults.
AB  - Between 1945 and 1955, several thousand patients were injected with Peteosthor, a
      preparation containing Radium-224 (Ra), as treatment for bone tuberculosis or
      ankylosing spondylitis. Ra, like Pu, is a bone seeking nuclide. During the course
      of early experimental work it became clear in 1948 that the short lived alpha
      emitter Ra concentrates predominantly in the growing zones of the bones.
      Consequently, I released strong official warnings, at the 1950 German Congress of
      Orthopedics, against Peteosthor, and especially against its administration to
      juvenile patients-still in their period of growth. Epidemiological investigations
      were then initiated on a study population that comprises 899 persons (including
      217 children or juveniles) who received injections of Ra. The study has now been
      conducted for a follow-up period of over 60 y. The most striking detrimental
      health effect following Ra injections are a large number of malignant bone tumors
      that occurred predominantly in childhood. This finding was the reason for my
      invitation to the first conference on "Delayed Effects of Bone seeking
      Radionuclides" in Sun Valley, ID, in September 1967, a meeting that was organized
      by Charles Mays. I reported on 50 Ra-induced bone tumors in children and adults,
      growth disturbances, osteochondroma, and cataracts, concluding that the younger
      the age at Ra injection, the more severe the late effects. Up to now 57 malignant
      bone tumors have been observed while less than one case would have been expected.
      The peak occurred 8 y after the first Ra injection and the last bone sarcoma
      arose 46 y after injection. A total of 270 non-skeletal malignant diseases were
      observed against a statistical expectation of 192 cases, the excess risk of
      mammary cancers in those treated in childhood being particularly striking. In the
      past two years increases of non-cancer diseases have become apparent in the
      exposed group compared to a control group of 166 living members with no exposure
      to Ra. Although 124 study group members are still alive, only the 81 members with
      ages at or below the maximum age in the control group were included in this
      comparison in order to attain approximate age matching. The breakdown of these
      diseases is kidney insufficiency, 12 (15%) study group members vs. 3 (2%)
      controls, where 5 (6%) study group members required dialysis vs. 2 (1%) controls;
      thyroid disease (struma nodosa), 28 (35%) study group members vs. 29 (17%)
      controls; heart attack, 8 (10%) study group members vs. 4 (2%) controls; coronary
      heart disease, 9 (11%) study group members vs. 8 (5%) controls.

PMID- 20699689
TI  - Radon and the risk of cancer mortality--internal Poisson models for the German
      uranium miners cohort.
AB  - Uranium mining occurred between 1946 and 1990 at the former Wismut mining company
      in East Germany. 58,987 male former employees form the largest single uranium
      miners cohort, which has been followed up for causes of mortality occurring from
      the beginning of 1946 to the end of 2003. The purpose of this paper is to present
      the radon exposure related cancer mortality risk based on 20,920 deaths, 2
      million person-years, and 6,373 cancers. The latter include 3,016 lung cancers
      and 3,053 extrapulmonary solid cancers. Internal Poisson regression was used to
      estimate the excess relative risk (ERR) per unit of cumulative radon exposure in
      Working Level Months (WLM) for all major sites and for the follow-up period from
      1946 to 2003. The simple cohort ERR WLM for lung cancer is 0.20% [95% confidence
      interval (CI): 0.17%; 0.22%]. The ERR model for lung cancer is linear in radon
      exposure with exponential effect modifiers that depend on age at median exposure,
      time since median exposure, and radon exposure-rate. In this model the central
      estimate of ERR WLM is 1.06% (95% CI: 0.69%; 1.42%) for an age at median exposure
      of 33 y, a time since median exposure of 11 y, and an exposure-rate of 2.7 WL.
      This central ERR decreases by 5% for each unit exposure-rate increase. The ERR
      decreases by 32% with each decade increase in age at median exposure and also
      decreases by 54% with each decade increase in time since median exposure. The ERR
      WLM for all extrapulmonary solid cancers combined without effect modification is
      0.014% (95% CI: 0.006%; 0.023%). The ERR model for extrapulmonary solid cancer is
      linear in radon exposure with an exponential effect modifier which depends on age
      attained. In this model the central estimate of ERR WLM is 0.040% (95% CI: 
      0.001%; 0.082%) for an age-attained of 44. The ERR decreases by 37% with each
      decade increase in age-attained. The highest ERR WLM, after lung, is observed for
      cancers of the pharynx (0.16%), tongue/mouth (0.045%), and liver (0.04%).

PMID- 20699690
TI  - Preliminary lung cancer risk assessment of exposure to radon progeny for
      Transylvania, Romania.
AB  - The objective of the present study was to assess the lung cancer risk induced by
      exposures to radon progeny of people living in some areas of Transylvania,
      Romania. Indoor radon concentrations were measured in 667 dwellings of Stei area,
      Cluj, Bistrita-Nasaud, Sibiu, and Alba counties. Measurements were performed
      using CR-39 track detectors, exposed for a minimum of 3 mo. Average annual radon
      concentrations were 232, 114, 71, 62, and 161 Bq m for Stei area, Cluj, Bistrita
      Nasaud, Sibiu, and Alba, respectively. The linear risk model of Darby was used to
      simulate the dose-effect relationship and relative lung cancer risk at low doses
      of alpha particles specific to residential radon exposures. Predicted relative
      risks at the measured exposure levels, together with information on the total
      number of reported lung cancer deaths and the number of people living in these
      regions, enabled us to estimate the fraction of lung cancer cases in each area
      that is attributable to radon. These percentages are 16.67% for Stei area, 9.09%
      for Cluj, 5.66% for Bistrita-Nasaud, 4.76% for Sibiu, and 12.28% for Alba county
      among lifetime non-smokers. Assuming that the smoking rates are similar for the
      investigated regions (10.72% smokers among men and 5.95% among women), around 64
      to 69% of the total number of annual lung cancer deaths, stratified by sex, would
      be attributed to radon and occur among smoking male population, and around 35 to
      44% would be attributed to radon and occur among smoking female population.

PMID- 20699691
TI  - Reprocessed uranium exposure and lung cancer risk.
AB  - This study investigated the risk of lung cancer in regards to protracted
      occupational exposure to reprocessed uranium compounds. Two thousand seven
      hundred and nine male workers employed at the AREVA NC uranium processing plant
      between 1960 and 2005 in France were included in the cohort. Historical exposure
      to reprocessed uranium compounds classified by their solubility type was assessed
      on the basis of the plant's specific job-exposure matrix. Cox proportional hazard
      models adjusted for attained age, calendar period, and socioeconomic status were
      used to estimate relative risks in regards of each type of uranium compound. The
      relative risk of lung cancer tended to increase with decreasing solubility of
      reprocessed uranium compounds. The highest-though not statistically significant
      relative risk was observed among workers exposed to slowly soluble reprocessed
      uranium dioxide. This study is the first suggesting an increasing risk of lung
      cancer associated with exposure to reprocessed uranium. Our results are
      consistent with data from experimental studies of biokinetics and the action
      mechanism of slowly soluble uranium compounds, but need to be confirmed in larger
      studies with more detailed dose-response analyses.

PMID- 20699692
TI  - Occupational and diagnostic exposure to ionizing radiation and leukemia risk
      among German uranium miners.
AB  - Lung cancer is a well-known effect of radon exposure in uranium mines. However,
      little is known about the induction of leukemia by radiation exposure in mines.
      Moreover, miners usually have occupational medical checkup programs that include
      chest x-ray examinations. Therefore, the aim of the present study was to re
      examine leukemia risk among miners, taking into account exposure to x rays for
      diagnostic purposes. The data used were from a previously analyzed individually
      matched case-control study of former uranium miners in East Germany with 377
      cases and 980 controls. Additionally, data on x-ray examinations were taken from
      medical records for most of the subjects. Finally, the absorbed dose to red bone
      marrow was calculated considering both occupational and diagnostic exposures.
      Using conditional logistic regression models, a moderately but not statistically
      significant elevated risk was seen in the dose category above 200 mGy for the
      combined dose from both sources [odds ratio (OR) = 1.33, 90% confidence interval
      (CI): (0.82-2.14)]. Ignoring the dose accumulated in the recent 20 y, the risk in
      the highest dose category (>105 mGy) was higher [OR = 1.77, 90% CI: (1.06-2.95)].
      Ignoring diagnostic exposure yielded similar results. For the highest dose
      category (absorbed dose lagged by 20 y) the risk was more than doubled [OR =
      2.64, 90% CI: (1.60-4.35)].

PMID- 20699693
TI  - Modeling deterministic effects in hematopoietic system caused by chronic exposure
      to ionizing radiation in large human cohorts.
AB  - A new model of the hematopoietic system for humans chronically exposed to
      ionizing radiation allows for quantitative description of the initial
      hematopoiesis inhibition and subsequent increase in the risks of late stochastic
      effects such as leukemia. This model describes the dynamics of the hematopoietic
      stem cell compartment as well as the dynamics of each of the three blood cell
      types (leukocytes, erythrocytes, and platelets). The model parameters are
      estimated from the results of other experiments. They include the steady-state
      numbers of hematopoietic stem cells and peripheral blood cell lines for an
      unexposed organism, amplification parameters for each blood cell line, parameters
      describing the proliferation and apoptosis, parameters of feedback functions
      regulating the steady-state numbers, and characteristics of radiosensitivity in
      respect to cell death and non-lethal cell damages. The dynamic model of
      hematopoiesis is applied to the data on a subcohort of the Techa River residents
      with hematological measurements (e.g., blood counts) performed in 1950-1956
      (which totals to about 3,500 exposed individuals). Among well-described effects
      observed in these data are the slope values of the dose-effect curves describing
      the hematopoietic inhibition and the dose rate patterns of the fractions of
      cytopenic states (e.g., leukopenia, thrombocytopenia). The model has been further
      generalized by inclusion of the component describing the risk of late stochastic
      effects. The risks of the development of late effects (such as leukemia) in
      population groups with specific patterns of early reactions in hematopoiesis
      (such as leukopenia induced by ionizing radiation) are investigated using
      simulation studies and compared to data.

PMID- 20699694
TI  - Early hematopoietic effects of chronic radiation exposure in humans.
AB  - The major goal of this study is to investigate and quantitatively describe the
      nature of the relationship between the characteristics of chronic exposure to
      ionizing radiation and specific patterns of hematopoiesis reduction. The study is
      based on about 3,200 hemograms taken for inhabitants of the Techa riverside
      villages over the years 1951-1956, i.e., the period characterized by a gradual
      decrease in dose rates. The mean cumulative red bone marrow dose was 333.6 + or -
      4.6 mGy. The approach to statistical analyses involved both empirical methods and
      modeling (generalized linear models and logistic regressions). The results of the
      analyses highlighted a gradual increase in the frequency of cytopenias with dose
      rate. The impact of exposure on hematopoiesis reduction patterns was found to be
      more substantial than that of age and health status. Dose rates resulting in a
      two-fold increase in the frequency of cytopenias have been estimated.

PMID- 20699695
TI  - Long-term cellular effects in humans chronically exposed to ionizing radiation.
AB  - The aim of the study was to investigate hematopoietic injury and recovery in
      residents of the Techa riverside villages who had been chronically exposed to
      radiation as a result of the activities of the Mayak Nuclear Facility, and
      evaluate late effects from chronic, low-dose radiation exposures. Whole blood
      samples were drawn from 338 unexposed individuals resident in noncontaminated
      villages, and 692 individuals chronically exposed externally (to primarily gamma
      radiation) and internally from Sr since 1949 at decreasing dose-rates which have
      currently reached the background levels. The mean cumulative dose in the exposed
      cohort was 0.62 Gy over the years 1949 to 2008 using the Techa River Dosimetry
      System (TRDS) 2000. The frequency of chromosome aberrations and mutations in
      peripheral lymphocytes, and other aspects indicative of cellular and molecular
      repair of radiation damage, were measured. The subjects were divided into two
      study groups: (a) 171 individuals who during the early exposure period (where the
      highest dose-rates were prevalent) were noted to manifest leucopenia and/or were
      diagnosed with chronic radiation syndrome (CRS), and (b) 521 exposed individuals
      without cytopenia and CRS. The first group demonstrated an increased frequency of
      micronuclei, dicentric chromosomes, somatic mutations (CD3-CD4+cells) in
      lymphocytes, and mutations in the TP53 gene. In addition, they demonstrated a
      lower Cu/Zn-SOD concentration, a significantly increased concentration of nitric
      oxide, and a greater apoptotic frequency in peripheral blood lymphocytes compared
      to exposed individuals without leucopenia. Similar to the unexposed individuals,
      the second group demonstrated "background levels" of mutational frequencies
      several years after their exposures, but they did show an increased number of
      cells with delayed cell cycles based on Chk-2 concentrations compared to the
      unexposed population. The data are consistent with the idea that a chronic
      radiation exposure within a dose range from 0.01 Gy to 1.96 Gy results in more
      severe late hematopoietic effects in a select cohort of highly radiosensitive
      individuals, rather than an overall increase in late effects in cells of each
      exposed individual. The authors state that radiation-exposed subjects
      demonstrating CRS showed an activation of barrier anti-oxidative stress
      mechanisms at late periods after radiation exposure, apparently in response to a
      more severe radiation damage than subjects exposed to similar radiation doses but
      not demonstrating CRS. Finally, the persistence of chromosome aberrations and
      somatic mutations in the CRS cohort is indicative of an exhaustion of the anti
      oxidative stress mechanisms responding for so many years after the exposure,
      leading to genomic instability.

PMID- 20699696
TI  - Late-occurring pulmonary pathologies following inhalation of mixed oxide (uranium
      + plutonium oxide) aerosol in the rat.
AB  - Accidental exposure by inhalation to alpha-emitting particles from mixed oxide
      (MOX: uranium and plutonium oxide) fuels is a potential long-term health risk to
      workers in nuclear fuel fabrication plants. For MOX fuels, the risk of lung
      cancer development may be different from that assigned to individual components
      (plutonium, uranium) given different physico-chemical characteristics. The
      objective of this study was to investigate late effects in rat lungs following
      inhalation of MOX aerosols of similar particle size containing 2.5 or 7.1%
      plutonium. Conscious rats were exposed to MOX aerosols and kept for their entire
      lifespan. Different initial lung burdens (ILBs) were obtained using different
      amounts of MOX. Lung total alpha activity was determined by external counting and
      at autopsy for total lung dose calculation. Fixed lung tissue was used for
      anatomopathological, autoradiographical, and immunohistochemical analyses.
      Inhalation of MOX at ILBs ranging from 1-20 kBq resulted in lung pathologies (90%
      of rats) including fibrosis (70%) and malignant lung tumors (45%). High ILBs (4
      20 kBq) resulted in reduced survival time (N = 102; p < 0.05) frequently
      associated with lung fibrosis. Malignant tumor incidence increased linearly with
      dose (up to 60 Gy) with a risk of 1-1.6% Gy for MOX, similar to results for
      industrial plutonium oxide alone (1.9% Gy). Staining with antibodies against
      Surfactant Protein-C, Thyroid Transcription Factor-1, or Oct-4 showed
      differential labeling of tumor types. In conclusion, late effects following MOX
      inhalation result in similar risk for development of lung tumors as compared with
      industrial plutonium oxide.

PMID- 20699697
TI  - Carcinogenesis from inhaled (239)PuO(2) in beagles: Evidence for radiation
      homeostasis at low doses?
AB  - From the early 1970's to the late 1980's, Pacific Northwest National Laboratory
      conducted life-span studies in beagle dogs on the biological effects of inhaled
      plutonium ((238)PuO(2), (239)PuO(2), and Pu[NO(3)](4)) to help predict risks
      associated with accidental intakes in workers. Years later, the purpose of the
      present follow-up study was to reassess the dose-response relationship for lung
      cancer in the PuO(2) dogs compared to controls-with particular focus on the dose
      response at relatively low lung doses. A PuO(2) aerosol (2.3 mum activity-median
      aerodynamic diameter, 1.9 mum geometric standard deviation) was administered to
      six groups of 20 young (18-mo-old) beagle dogs (10 males and 10 females) by
      inhalation at six different activity levels, as previously described in
      Laboratory reports. Control dogs were sham-exposed. In dose level 1, initial
      pulmonary lung depositions were 130 + or - 48 Bq (3.5 + or - 1.3 nCi),
      corresponding to 1 Bq g lung tissue (0.029 + or - 0.001 nCi g(-1)). Groups 2
      through 6 received initial lung depositions (mean values) of 760, 2,724, 10,345,
      37,900, and 200,000 Bq (22, 79, 300, 1,100, and 5,800 nCi) PuO(2), respectively.
      For each dog, the absorbed dose to lungs was calculated from the initial lung
      burden and the final lung burden at time of death and lung mass, assuming a
      single, long-term retention function. Insoluble plutonium oxide exhibited long
      retention times in the lungs. Increased dose-dependent mortality due to lung
      cancer (bronchiolar-alveolar carcinoma, adenocarcinoma, and epidermoid carcinoma)
      and radiation pneumonitis (in the highest exposure group) were observed in dogs
      exposed to PuO(2). Calculated lung doses ranged from a few cGy (lowest exposure
      level) to 7,764 cGy in dogs that experienced early deaths from radiation
      pneumonitis. Data were regrouped by lifetime lung dose and plotted as a function
      of lung tumor incidence. The lung tumor incidence in controls and zero-dose
      exposed dogs was 18% (5/28). However, no lung tumors were observed in 16 dogs
      with the lowest lung doses (8 to 22 cGy, mean 14.4 + or - 7.6 cGy), and only one
      lung tumor was observed in the next 10 dogs with lung doses ranging from 27 to 48
      cGy (mean 37.5 + or - 10.9 cGy). By least-squares analysis, a pure-quadratic
      function represented the overall dose-response (n = 137, r = 0.96) with no
      apparent dose-related threshold. Reducing this function to three linear dose
      response components, we calculated risk coefficients for each. However, the
      incidence of lung tumors at zero dose was significantly greater than the
      incidence at low dose (at the p < or = 0.053 confidence level), suggesting a
      protective effect (radiation homeostasis) of alpha-particle radiation from
      PuO(2). If a threshold for lung cancer incidence exists, it will be observed in
      the range 15 to 40 cGy.

PMID- 20699698
TI  - Comparative stochastic effects of alpha, beta or x-irradiation of the lung of
      rats.
AB  - The stochastic effects in the lung of inhaled, insoluble particles of alpha- and
      beta-emitting particles and low-linear energy transfer (LET) thoracic irradiation
      were compared in rats using data from previously conducted studies. Male and
      female F344 rats were exposed briefly by nasal inhalation to relatively insoluble
      aerosols of CeO(2) or PuO(2) to achieve a range of four lung burdens. The mean
      lifetime beta doses to the lung were 3.6 + or - 1.3 Gy, 6.8 + or - 1.7 Gy, 12 +
      or - 4.5 Gy, and 37 + or - 5.9 Gy. The mean lifetime alpha doses to the lung were
      0.06 + or - 0.03 Gy, 0.95 + or - 0.46 Gy, 3.7 + or - 1.6 Gy, and 12 + or - 2.4
      Gy. Additional rats were exposed to fractionated thoracic doses of x rays given
      on 10 successive working days. The lifetime doses to the lung were 3.3 Gy, 5.7
      Gy, 11 Gy, and 38 Gy. Appropriate sham controls were included in each group and
      all groups were observed for their life spans. Lung neoplasms were found after
      all exposures, with the incidence increasing with radiation dose. Rats exposed to
      PuO(2) had the highest incidence, 94% in the group with a dose of 12 Gy. The
      incidence in the groups exposed to inhaled CeO(2) or fractionated thoracic x
      irradiation was not significantly different. The incidence of lung tumors in the
      PuO(2) groups was 21 times higher than that of the groups exposed to the lower
      LET radiations. These results support a radiation-weighting factor of 20, as
      recommended by ICRP 60.

PMID- 20699699
TI  - Determining the relative toxicity and RBE of internal emitters in animals.
AB  - It is almost impossible to conduct a perfect study of the relative toxicity of
      the radiations produced by different radionuclides. This is because the results
      of such studies are commonly confounded by spatial and temporal differences in
      the distributions of dose produced by the radionuclides employed. In addition,
      the results of a study designed to overcome these problems (using matched
      radionuclides incorporated within fused clay particles) revealed additional
      characteristics of an ideal study. These included the use of sufficient numbers
      of animals to give the study statistical power; the derivation of all causes of
      death and of survival for the analysis; the use of relative risk, rather than
      crude incidence data, to determine toxicity ratios; the cautious use of relative
      biological effectiveness values derived from fitted curves; and the preferred use
      of relative toxicity values derived directly from the data.

PMID- 20699700
TI  - Preconceptional paternal exposure to depleted uranium: transmission of genetic
      damage to offspring.
AB  - Depleted uranium (DU) is an alpha particle emitter and radioactive heavy metal
      used in military applications. Due to internalization of DU during military
      operations and the ensuing chronic internal exposure to DU, there are concerns
      regarding its potential health effects. Preconceptional paternal irradiation has
      been implicated as a causal factor in childhood cancer and it has been suggested
      that this paternal exposure to radiation may play a role in the occurrence of
      leukemia and other cancers to offspring. Similarly, in vivo heavy metal studies
      have demonstrated that carcinogenic effects can occur in unexposed offspring.
      Using a transgenic mouse system employing a lambda shuttle vector allowing
      mutations (in the lacI gene) to be analyzed in vitro, we have investigated the
      possibility that chronic preconceptional paternal DU exposure can lead to
      transgenerational transmission of genomic instability. The mutation frequencies
      in vector recovered from the bone marrow cells of the F1 offspring of male
      parents exposed to low, medium, and high doses of internalized DU for 7 mo were
      evaluated and compared to control, tantalum, nickel, and gamma radiation F1
      samples. Results demonstrate that as paternal DU-dose increased there was a trend
      towards higher mutation frequency in vector recovered from the DNA obtained from
      bone marrow of F1 progeny; medium and high dose DU exposure to P1 fathers
      resulted in a significant increase in mutation frequency in F1 offspring (3.57
      +or - 0.37 and 4.81 + or - 0.43 x 10; p < 0.001) in comparison to control (2.28 +
      or - 0.31 x 10). The mutation frequencies from F1 offspring of low dose DU, Ta-
      or Ni-implanted fathers (2. 71 + or - 0.35, 2.38 + or - 0.35, and 2.93 + or -
      0.39 x 10, respectively) were not significantly different than control levels
      (2.28 + or - 0.31 x 10). Offspring from Co (4 Gy) irradiated fathers did
      demonstrate an increased lacI mutation frequency (4.69 + or - 0.48 x 10) as had
      been shown previously. To evaluate the role of radiation involved in the observed
      DU effects, males were exposed to equal concentrations (50 mg U L) of either
      enriched uranium or DU in their drinking water for 2 mo prior to breeding. A
      comparison of these offspring indicated that there was a specific-activity
      dependent increase in offspring bone marrow mutation frequency. Taken together
      these uranyl nitrate data support earlier results in other model systems showing
      that radiation can play a role in DU-induced biological effects in vitro.
      However, since the lacI mutation model measures point mutations and cannot
      measure large deletions that are characteristic of radiation damage, the role of
      DU chemical effects in the observed offspring mutation frequency increase may
      also be significant. Regardless of the question of DU-radiation vs. DU-chemical
      effects, the data indicate that there exists a route for transgenerational
      transmission of factor(s) leading to genomic instability in F1 progeny from DU
      exposed fathers.

PMID- 20699701
TI  - Isotopic and elemental composition of plutonium/americium oxides influence
      pulmonary and extra-pulmonary distribution after inhalation in rats.
AB  - The biodistribution of plutonium and americium has been studied in a rat model
      after inhalation of two PuO(2) powders in lungs and extra-pulmonary organs from 3
      d to 3 mo. The main difference between the two powders was the content of
      americium (approximately 46% and 4.5% of total alpha activity). The PuO(2) with a
      higher proportion of americium shows an accelerated transfer of activity from
      lungs to blood as compared to PuO(2) with the lower americium content,
      illustrated by increased urinary excretion and higher bone and liver actinide
      retention. The total alpha activity measured reflects mostly the americium
      biological behavior. The activity contained in epithelial lining fluid, recovered
      in the acellular phase of broncho-alveolar lavages, mainly contains americium,
      whereas plutonium remains trapped in macrophages. Epithelial lining fluid could
      represent a transitional pulmonary compartment prior to translocation of
      actinides to the blood and subsequent deposition in extra-pulmonary retention
      organs. In addition, differential behaviors of plutonium and americium are also
      observed between the PuO(2) powders with a higher dissolution rate for both
      plutonium and americium being obtained for the PuO(2) with the highest americium
      content. Our results indicate that the biological behavior of plutonium and
      americium after translocation into blood differ two-fold: (1) for the two
      actinides for the same PuO(2) aerosol, and (2) for the same actinide from the two
      different aerosols. These results highlight the importance of considering the
      specific behavior of each contaminant after accidental pulmonary intake when
      assessing extra-pulmonary deposits from the level of activity excreted in urine
      or for therapeutic strategy decisions.

PMID- 20699702
TI  - The uneven irradiation of a target cell and its dynamic movement can
      mathematically explain incubation period for the induction of cancer by
      internally deposited radionuclides.
AB  - Irradiation from internally deposited radionuclides induces malignant tumors.
      Ingested radionuclides accumulate in specific organs, which are irradiated over a
      lifelong period. Our aim is to elucidate why the development of malignant tumors
      requires long-term internal exposure, on the order of decades, despite the fact
      that irradiation is continuous over this period. Three major factors are
      considered to be responsible for the long incubation time in carcinogenesis
      caused by internally deposited alpha-emitters: uneven distribution of
      radionuclides, limited range of irradiation, and dynamic movement of tumor
      precursor cells. We hypothesized that target cells susceptible to malignant
      transformation may undergo one event by alpha particles and may then migrate
      outside of the range of alpha particles, thereby avoiding immediate induction of
      successive additional events that would lead to cell death or neoplastic changes.
      Based on this hypothesis, we further proposed a mathematical model to predict the
      relationship between dose rate and incubation period of tumors induced by
      internally deposited alpha-emitters. The function was non-linear and included
      terms of both direct and indirect radiation effects. It well fitted both human Th
      ICC cases and rat Pu-induced lung cancer, suggesting that indirect radiation
      effects are independent from dose rate. The significance of parameters of the
      model is discussed.

PMID- 20699703
TI  - Biomaterials for the decorporation of (85)Sr in the rat.
AB  - Although four stable isotopes of strontium occur naturally, Sr is produced by
      nuclear fission and is present in surface soil around the world as a result of
      fallout from atmospheric nuclear weapons tests. It can easily transfer to humans
      in the event of a nuclear/radiological emergency or through the plant-animal
      human food chain causing long-term exposures. Strontium is chemically and
      biologically similar to calcium, and is incorporated primarily into bone
      following internal deposition. Alginic acid (alginate) obtained from seaweed
      (kelp) extract selectively binds ingested strontium in the gastrointestinal tract
      blocking its systemic uptake and reducing distribution to bone in rats, while
      other natural polysaccharides including chitosan and hyaluronic acid had little
      in vivo affinity for strontium. Alginate exhibits the unique ability to
      discriminate between strontium and calcium and has been previously shown to
      reduce intestinal absorption and skeletal retention of strontium without changing
      calcium metabolism. In our studies, the effect of commercially available alginate
      on intestinal absorption of strontium was examined. One problem associated with
      alginate treatment is its limited solubility and gel formation in water. The
      aqueous solubility of sodium alginate was improved in a sodium chloride/sodium
      bicarbonate electrolyte solution containing low molecular weight polyethylene
      glycol (PEG). Furthermore, oral administration of the combined
      alginate/electrolyte/PEG solution accelerated removal of internal strontium in
      rats when compared to treatment with individual sodium alginate/electrolyte or
      electrolyte/PEG solutions. Importantly, both alginate and PEG are nontoxic,
      readily available materials that can be easily administered orally in case of a
      national emergency when potentially large numbers of the population may require
      medical treatment for internal depositions. Our results suggest further studies
      to optimize in vivo decorporation performance of engineered alginate material via
      modification of its chemical and physicochemical properties are warranted.

PMID- 20699704
TI  - Biomimetic actinide chelators: an update on the preclinical development of the
      orally active hydroxypyridonate decorporation agents 3,4,3-LI(1,2-HOPO) and 5
      LIO(Me-3,2-HOPO).
AB  - The threat of a dirty bomb or other major radiological contamination presents a
      danger of large-scale radiation exposure of the population. Because major
      components of such contamination are likely to be actinides, actinide
      decorporation treatments that will reduce radiation exposure must be a priority.
      Current therapies for the treatment of radionuclide contamination are limited and
      extensive efforts must be dedicated to the development of therapeutic, orally
      bioavailable, actinide chelators for emergency medical use. Using a biomimetic
      approach based on the similar biochemical properties of plutonium(IV) and
      iron(III), siderophore-inspired multidentate hydroxypyridonate ligands have been
      designed and are unrivaled in terms of actinide-affinity, selectivity, and
      efficiency. A perspective on the preclinical development of two hydroxypyridonate
      actinide decorporation agents, 3,4,3-LI(1,2-HOPO) and 5-LIO(Me-3,2-HOPO), is
      presented. The chemical syntheses of both candidate compounds have been optimized
      for scale-up. Baseline preparation and analytical methods suitable for
      manufacturing large amounts have been established. Both ligands show much higher
      actinide-removal efficacy than the currently approved agent,
      diethylenetriaminepentaacetic acid (DTPA), with different selectivity for the
      tested isotopes of plutonium, americium, uranium and neptunium. No toxicity is
      observed in cells derived from three different human tissue sources treated in
      vitro up to ligand concentrations of 1 mM, and both ligands were well tolerated
      in rats when orally administered daily at high doses (>100 micromol kg d) over 28
      d under good laboratory practice guidelines. Both compounds are on an accelerated
      development pathway towards clinical use.

PMID- 20699705
TI  - Pharmacological properties of orally available, amphipathic polyaminocarboxylic
      acid chelators for actinide decorporation.
AB  - Commonly used water-soluble polyaminocarboxylic acid (PACA) chelators, such as
      EDTA and DTPA, require intravenous or subcutaneous administration due to their
      poor bioavailability. The bioavailability of PACAs can be improved by the
      addition of differing lengths of alkyl side chains that alter amphipathic
      properties. Orally administered amphipathic triethylenetetramine pentaacetic acid
      (TT) compounds are efficacious for decorporation of plutonium and americium. The
      synthesis, efficacy, binding affinities, and some initial pharmacokinetics
      properties of amphipathic TT chelators are reviewed. C-labeled C12TT and C22TT
      chelators are reasonably well absorbed from the intestine and have a substantial
      biliary/fecal excretion pathway, unlike DTPA, which is mostly excreted in the
      urine. Whole body retention times are increased as a function of increasing
      lipophilicity. Neutron-induced autoradiography studies demonstrate that the oral
      administration of the chelators can substantially inhibit the redistribution of
      Pu in skeletal tissues. In summary, amphipathic TT-based chelators have favorable
      bioavailability, have a significant biliary excretion pathway, have demonstrated
      efficacy for americium and plutonium, and are thus good candidates for further
      development. Furthermore, some of the pharmacological properties can be
      manipulated by changing the lengths of the alkyl side chains and this may have
      some advantage for decorporation of certain metals and radionuclides.

PMID- 20699706
TI  - Functional sorbents for selective capture of plutonium, americium, uranium, and
      thorium in blood.
AB  - Self-assembled monolayer on mesoporous supports (SAMMS) are hybrid materials
      created from attachment of organic moieties onto very high surface area
      mesoporous silica. SAMMS with surface chemistries including three isomers of
      hydroxypyridinone, diphosphonic acid, acetamide phosphonic acid, glycinyl urea,
      and diethylenetriamine pentaacetate (DTPA) analog were evaluated for chelation of
      actinides ((239)Pu, (241)Am, uranium, thorium) from blood. Direct blood
      decorporation using sorbents does not have the toxicity or renal challenges
      associated with traditional chelation therapy and may have potential applications
      for critical exposure cases, reduction of nonspecific dose during actinide
      radiotherapy, and for sorbent hemoperfusion in renal insufficient patients, whose
      kidneys clear radionuclides at a very slow rate. Sorption affinity (K(d)),
      sorption rate, selectivity, and stability of SAMMS were measured in batch contact
      experiments. An isomer of hydroxypyridinone (3,4-HOPO) on SAMMS demonstrated the
      highest affinity for all four actinides from blood and plasma and greatly
      outperformed the DTPA analog on SAMMS and commercial resins. In batch contact, a
      fifty percent reduction of actinides in blood was achieved within minutes, and
      there was no evidence of protein fouling or material leaching in blood after 24
      h. The engineered form of SAMMS (bead format) was further evaluated in a 100-fold
      scaled-down hemoperfusion device and showed no blood clotting after 2 h. A 0.2 g
      quantity of SAMMS could reduce 50 wt.% of 100 ppb uranium in 50 mL of plasma in
      18 min and that of 500 dpm mL(-1) in 24 min. 3,4-HOPO-SAMMS has a long shelf-life
      in air and at room temperature for at least 8 y, indicating its feasibility for
      stockpiling in preparedness for an emergency. The excellent efficacy and
      stability of SAMMS materials in complex biological matrices suggest that SAMMS
      can also be used as orally administered drugs and for wound decontamination. By
      changing the organic groups of SAMMS, they can be used not only for actinides but
      also for other radionuclides. By using the mixture of these SAMMS materials,
      broad spectrum decorporation of radionuclides is very feasible.

PMID- 20699707
TI  - In vitro and in vivo evaluation of a novel ferrocyanide functionalized
      nanopourous silica decorporation agent for cesium in rats.
AB  - Novel decorporation agents are being developed to protect against radiological
      terrorist attacks. These sorbents, known as the self-assembled monolayer on
      mesoporous supports (SAMMS), are hybrid materials where differing organic
      moieties are grafted onto mesoporous silica (SiO(2)). In vitro experiments
      focused on the evaluation and optimization of SAMMS for capturing radiocesium
      ((137)Cs); therefore, based on these studies, a ferrocyanide copper (FC-Cu-EDA)
      SAMMS was advanced for in vivo evaluation. In vivo experiments were conducted
      comparing the performance of the SAMMS vs. insoluble Prussian blue. Groups of
      jugular cannulated rats (4/treatment) were evaluated. Animals in Group I were
      administered (137)Cs chloride (approximately 40 microg kg(-1)) by intravenous
      (i.v.) injection or oral gavage; Group II animals were administered pre-bound
      (137)Cs-SAMMS or sequential Cs chloride + SAMMS (approximately 61 ng kg(-1)) by
      oral gavage; and Group III was orally administered (137)Cs chloride
      (approximately 61 ng kg(-1)) followed by either 0.1 g of SAMMS or Prussian blue.
      Following dosing, the rats were maintained in metabolism cages for 72 h and
      blood, urine, and fecal samples were collected for (137)Cs analysis (gamma
      counting). Rats were then humanely euthanized, and selected tissues analyzed.
      Orally administered (137)Cs chloride was rapidly and well absorbed (approximately
      100% relative to i.v. dose), and the pharmacokinetics (blood, urine, feces, and
      tissues) were very comparable to the i.v. dose group. For both exposures the
      urine and feces accounted for 20 and 3% of the dose, respectively. The prebound
      (137)Cs-SAMMS was retained primarily within the feces (72% of the dose), with
      approximately 1.4% detected in the urine, suggesting that the (137)Cs remained
      tightly bound to SAMMS. SAMMS and Prussian blue both effectively captured
      available (137)Cs in the gut with feces accounting for 80-88% of the administered
      dose, while less than 2% was detected in the urine. This study suggests that the
      functionalized SAMMS outperforms Prussian blue in vitro at low pH, but
      demonstrates comparable in vivo sequestration efficacy at low exposure
      concentrations. The comparable response may be the result of the low (137)Cs
      chloride dose and high sorbent dosage that was utilized. Future studies are
      planned to optimize the performance of SAMMS in vivo over a broader range of
      doses and conditions.

PMID- 20699708
TI  - A new formulation containing calixarene molecules as an emergency treatment of
      uranium skin contamination.
AB  - Cutaneous contamination represents the second highest contamination pathway in
      the nuclear industry. Despite that the entry of actinides such as uranium into
      the body through intact or wounded skin can induce a high internal exposure, no
      specific emergency treatment for cutaneous contamination exists. In the present
      work, an innovative formulation dedicated to uranium skin decontamination was
      developed. The galenic form consists in an oil-in-water nanoemulsion, which
      contains a tricarboxylic calixarene known for its high uranium affinity and
      selectivity. The physicochemical characterization of this topical form revealed
      that calixarene molecules are located at the surface of the dispersed oil
      droplets of the nanoemulsion, being thus potentially available for uranium
      chelation. It was demonstrated in preliminary in vitro experiments by using an
      adapted ultrafiltration method that the calixarene nanoemulsion was able to
      extract and retain more than 80% of uranium from an aqueous uranyl nitrate
      contamination solution. First ex vivo experiments carried out in Franz diffusion
      cells on pig ear skin explants during 24 h showed that the immediate application
      of the calixarene nanoemulsion on a skin contaminated by a uranyl nitrate
      solution allowed a uranium transcutaneous diffusion decrease of about 98% through
      intact and excoriated skins. The calixarene nanoemulsion developed in this study
      thus seems to be an efficient emergency system for uranium skin decontamination.

PMID- 20699711
TI  - Impact of depression on drug intake in hypertensive patients.

PMID- 20699712
TI  - Blood pressure up in a puff of smoke.

PMID- 20699713
TI  - Sympathoexcitation in calcineurin inhibitor-induced hypertension: villain or
      innocent bystander?

PMID- 20699714
TI  - Media-to-lumen ratio as predictor of renal abnormalities in hypertension: new
      findings, new questions.

PMID- 20699715
TI  - FAD286, an aldosterone synthase inhibitor, reduced atherosclerosis and
      inflammation in apolipoprotein E-deficient mice.
AB  - INTRODUCTION: Aldosterone is known to be involved in atherosclerosis and
      cardiovascular disease and blockade of its receptor was shown to improve
      cardiovascular function. It was, therefore, hypothesized that inhibition of
      aldosterone synthesis would also reduce atherosclerosis development. METHOD: To
      test this hypothesis, we examined the effect of FAD286 (FAD), an aldosterone
      synthase inhibitor, on the development of atherosclerosis in spontaneous
      atherosclerotic apolipoprotein E-deficient mice. Mice were divided into three
      treatment groups: normal diet, low-salt diet (LSD) and LSD treated with FAD at 30
      mg/kg per day (LSD + FAD) for 10 weeks. RESULTS AND CONCLUSION: Histomorphometry
      of the aortas obtained from these mice showed that atherosclerotic lesion area
      increased by three-fold under LSD compared with normal diet and FAD significantly
      reduced lesion area to values similar to normal diet. Changes in atherosclerosis
      were paralleled by changes in the expression of the inflammation markers (C
      reactive protein, monocyte chemotactic protein-1, interleukin-6, nuclear factor
      kappa B and intercellular adhesion molecule-1) in peritoneal macrophages obtained
      from these mice. Surprisingly, whereas LSD increased serum or urine aldosterone
      levels, FAD did not alter these levels when evaluated at the end of the study. In
      J774A.1 macrophage-like cell line stimulated with lipopolysaccharide, FAD was
      shown to have a direct dose-dependent anti-inflammatory effect. In apolipoprotein
      E-deficient mice, FAD reduces atherosclerosis and inflammation. However, these
      actions appeared to be dissociated from its effect on inhibition of aldosterone
      synthesis.

PMID- 20699716
TI  - The mental health impact of volunteering in a disaster setting: a review.
AB  - This article reviews the literature on mental health of volunteers after working
      in disasters. When mobilized they often are a community's major source for rescue
      and recovery. PsychINFO, PubMED, and Web of Science were searched for relevant
      articles published until October 2009. Of 448 articles screened, only 9 articles
      fulfilled our inclusion criteria. They examined the aftermath of earthquakes (4
      articles), terrorist bombings (1), explosions (1), aviation disasters (1),
      tsunami (1), and a bus accident (1).Findings showed that, compared with
      professional workers, volunteers tend to have higher complaint levels. The
      following factors were found to contribute to mental health complaints of
      volunteers: Identification with victims as a friend, severity of exposure to
      gruesome events during disaster work, anxiety sensitivity, and lack of
      postdisaster social support. The review reveals the need for more research
      regarding predictors of stress in volunteers.

PMID- 20699717
TI  - The 9/11 terrorist attack and posttraumatic stress disorder revisited.
AB  - Research published in the aftermath of the 9/11 terrorist attack reported
      elevated rates of posttraumatic stress disorder (PTSD) in the US population (4.3%
      17.0%), attributable to indirect exposure through the media. We use data from a
      national survey conducted in 2004 to 2005 (National Epidemiologic Survey on
      Alcohol and Related Conditions Wave 2) (n = 34,653). The list of traumatic events
      covered in the survey included indirect exposure to 9/11 through media coverage.
      Respondents who endorsed more than 1 traumatic event were asked to single out
      "the worst event" they had ever experienced. The worst event (or the only event)
      was the index event for diagnosing PTSD. Indirect experience of 9/11 had the
      lowest PTSD risk of all the traumatic events in the list, 1.3%. In the subset
      that endorsed only 9/11 indirect exposure (n = 3981), the PTSD risk was 0.3%. Of
      the total sample, 0.7% experienced PTSD in relation to indirect 9/11.
      Explanations for the lower estimates are discussed.

PMID- 20699718
TI  - Use of benzodiazepines, hypnotics, and anxiolytics in major depressive disorder:
      association with chronic pain diseases.
AB  - We examined the use of benzodiazepines (BZD), hypnotics, and anxiolytics and
      their associations with chronic pain diseases (CPD) in patients with major
      depressive disorder (MDD). A retrospective analysis of 153,913 MDD patients (18
      64 years) in a large administrative insured claims database during the year 2006
      was performed. Results showed that during the study year, 33.1% of the patients
      had been prescribed BZD; 16.9%, hypnotics; and 6.1%, anxiolytics. The use of BZD
      and hypnotics increased with age. Patients with CPD were more likely than those
      without CPD to use BZD (41.2% vs. 27.0%, p < 0.001), hypnotics (21.7% vs. 13.3%,
      p < 0.001), and anxiolytics (7.8% vs. 4.8%, p < 0.01). After adjustment for
      demographics and comorbidities, CPD was still significantly associated with
      increased use of BZD (OR = 1.62), hypnotics (OR = 1.49), and anxiolytics (OR =
      1.51). Further research is needed to examine the long-term benefits and risks of
      BZD and hypnotics in the treatment of MDD and CPD.

PMID- 20699719
TI  - A cross-ethnic comparison of lifetime prevalence rates of anxiety disorders.
AB  - To examine race-ethnic differences in the lifetime prevalence rates of common
      anxiety disorders, we examined data from the Collaborative Psychiatric
      Epidemiology Studies. The samples included 6870 White Americans, 4598 African
      Americans, 3615 Hispanic Americans, and 1628 Asian Americans. White Americans
      were more likely to be diagnosed with social anxiety disorder, generalized
      anxiety disorder, and panic disorder than African Americans, Hispanic Americans,
      and Asian Americans. African Americans more frequently met criteria for post
      traumatic stress disorder (PTSD) than White Americans, Hispanic Americans, and
      Asian Americans. Asian Americans were also less likely to meet the diagnoses for
      generalized anxiety disorder and PTSD than Hispanic Americans, and were less
      likely to receive social anxiety disorder, generalized anxiety disorder, panic
      disorder, and PTSD diagnoses than White Americans. The results suggest that race
      and ethnicity need to be considered when assigning an anxiety disorder diagnosis.
      Possible reasons for the observed differences in prevalence rates between racial
      groups are discussed.

PMID- 20699720
TI  - Client predictors of employment outcomes in high-fidelity supported employment: a
      regression analysis.
AB  - Research on vocational rehabilitation for clients with severe mental illness over
      the past 2 decades has yielded inconsistent findings regarding client factors
      statistically related to employment. The present study aimed to elucidate the
      relationship between baseline client characteristics and competitive employment
      outcomes-job acquisition and total weeks worked during an 18-month follow-up-in
      Individual Placement and Support (IPS). Data from 4 recent randomized controlled
      trials of IPS were aggregated for within-group regression analyses. In the IPS
      sample (N = 307), work history was the only significant predictor for job
      acquisition, but receiving Supplemental Security Income-with or without Social
      Security Disability Insurance-was associated with fewer total weeks worked (2.0%
      2.8% of the variance). In the comparison sample (N = 374), clients with a
      diagnosis of mood disorder or with less severe thought disorder symptoms were
      more likely to obtain competitive employment. The findings confirm that clients
      with severe mental illness interested in competitive work best benefit from high
      fidelity supported employment regardless of their work history and
      sociodemographic and clinical background, and highlight the needs for changes in
      federal policies for disability income support and insurance regulations.

PMID- 20699721
TI  - Autobiography as tool to improve lifestyle, well being, and self-narrative in
      patients with mental disorders.
AB  - The aims of the present study were to explore how the autobiographical process
      can lead to a transformation in psychiatric patients' lifestyle, well-being, and
      self-narrative. Nine participants, aged between 20 and 42 years and affected by
      axis I psychiatric disorders (DSM IV) were selected to participate in an
      autobiographical laboratory. Eight to 10 meetings took place, each lasting about
      an hour, during which autobiographical accounts were collected. At the beginning
      and end of the autobiographical laboratory, the medical staff completed the
      Social Functioning Scale to evaluate each patient across 6 dimensions: social
      engagement, interpersonal ability, prosocial activities, recreation, independence
      competence, and independence-performance. The Language Inquiry and Word Count
      (Pennebaker and Francis, 1996) was used to analyze patients' autobiographical
      accounts. A comparison between the first and second compilation of the Social
      Functioning Scale showed significant positive changes across the 6 social
      dimensions. The analysis of language in the narratives collected in the first and
      seventh meeting showed how inpatients passed from a narrative that was more
      centered on the memory of the past to a narrative that was more similar to a
      conversation and enriched with "insight" terms and the use of verbs in the
      conjunctive form. The authors interpret these outcomes as being consistent with
      the improvement that was observed in inpatients' social functioning.

PMID- 20699722
TI  - Factors correlated with client attachment to mental health services.
AB  - This study aimed to explore clients' attachments to psychiatric rehabilitation
      services and associations with adult attachment style and severity of symptoms.
      Potential correlates of attachments to services were investigated using a cross
      sectional design. A total of 78 participants from inpatient rehabilitation units
      completed measures of attachment to mental health services, adult attachment
      style, depression, and psychosis. Clients with a more insecure attachment style
      and greater severity of depression indicated lower levels of attachment to
      services, although no effects were found for severity of psychotic symptoms.
      Patients with insecure adult attachment styles and higher levels of depression
      may experience particular difficulties in developing secure attachments to
      services.

PMID- 20699723
TI  - Is mood affected by interactions with people at risk for affective disorders?
AB  - The interpersonal behavior of individuals who have affective disorders can
      increase the likelihood of interpersonal conflicts. A related issue is whether
      vulnerability for developing affective disorder expresses itself in social
      interactions that affect the mood of interaction partners as well. Adolescents (n
      = 119) have been divided into subgroups: "mania risk" (scoring high on "Hypomanic
      Personality"); "unipolar risk" (scoring high on "Rigidity"); and a control group
      (scoring low on both scales). Interviews were conducted by raters blind to risk
      status. Interviewers provided ratings of their own mood before and after the
      interview. Negative mood of the interviewers did not change. Interviewers'
      positive mood decreased when interacting with individuals at risk for unipolar
      disorder as well as when interacting with the control subjects, but not when
      interacting with people at risk for mania. It seems that individuals high in
      hypomanic traits keep the interaction partner longer engaged and interested.

PMID- 20699724
TI  - IQ subtypes in schizophrenia: distinct symptom and neuropsychological profiles.
AB  - Intellectual decline, a key component of cognitive impairment in schizophrenia,
      varies considerably across individuals. To examine such cognitive heterogeneity,
      we applied cluster analysis of IQ and oral reading scores in 73 patients with
      schizophrenia. The following 3 empirically-derived subtypes emerged:
      intellectually compromised (42%) with similarly subaverage IQ (M = 79.90) and
      oral reading (M = 84.03); intellectually deteriorated (29%) with subaverage IQ (M
      = 86.81) but average oral reading (M = 107.71); and intellectually preserved
      (29%) with average IQ (M = 108.38) and oral reading (M = 104.43). Compromised and
      deteriorated clusters showed impairments in both executive function and memory,
      whereas the preserved cluster showed only reduced executive functioning. The 3
      clusters also differed in symptom patterns; with intellectually compromised and
      intellectually deteriorated both rated with higher negative than positive
      symptoms, in contrast to the opposite pattern of intellectually preserved.
      Cluster symptom and neuropsychological profiles may help to validate empirically
      derived IQ subtypes in schizophrenia.

PMID- 20699725
TI  - The value of social attributes of stimuli for promoting engagement in persons
      with dementia.
AB  - The present study examined the impact of different attributes of social stimuli
      using the stimulus attributes aspect of the Comprehensive Process Model of
      Engagement ( Am J Geriatr Psychiatry. 17:299-307). Participants were 193
      residents of 7 Maryland nursing homes with a diagnosis of dementia. Stimuli were
      chosen to represent different levels of the following social attributes: social
      versus not social, realistic versus not realistic, animated versus nonanimated,
      human versus nonhuman, and alive versus not alive. Participants had significantly
      longer engagement, were significantly more attentive, and displayed a
      significantly more positive attitude with social stimuli than with nonsocial
      stimuli. Longer durations and higher ratings of attention and attitude were seen
      with realistic and animated stimuli as compared to their counterparts. Human and
      live stimuli resulted in significantly more engagement than their counterparts.
      Giving any social stimulus to the residents is preferable to providing none, and
      the social attributes of stimuli should be maximized.

PMID- 20699726
TI  - Dream recall and dream content in obsessive-compulsive patients: is there a
      change during exposure treatment?
AB  - Very little is known about dreams in patients with obsessive compulsive disorder,
      especially regarding changes over the course of treatment with stimulus exposure
      and response prevention. By use of dream content analysis, 40 dreams of 9
      obsessive compulsive (OC) inpatients were compared with 84 dreams of 10 matched
      OC outpatients and 63 dreams of 11 healthy control participants. Dream protocols
      of inpatients were collected at the beginning of treatment and after the first
      exposure exercises. Controls filled in dream protocols in respective intervals.
      Before treatment, dreams of patients showed significantly less positive contents
      than dreams of healthy controls. Under treatment with exposure, a significant
      reduction of OC themes was observed. The findings support the continuity
      hypothesis of dreaming by showing a link between day-time symptoms and OC
      symptoms in dreams. Contrary to expectations, however, exposure treatment does
      not intensify dreams.

PMID- 20699727
TI  - Interpersonal psychotherapy for women with comorbid depression and chronic pain.
AB  - Chronic pain is prevalent among patients with depression and a risk factor for
      poor depression treatment outcomes. No known psychotherapy approaches have been
      developed to target the needs of patients with comorbid depression and chronic
      pain. This study's goals were to evaluate feasibility, acceptability, and initial
      effects of interpersonal psychotherapy adapted for women with depression and
      chronic pain. Seventeen women with major depression and chronic pelvic pain were
      offered 8 sessions of individual treatment, interpersonal psychotherapy for
      depression and pain (IPT-P). Participants were recruited from a women's health
      clinic, were predominantly low-income and minority, and generally did not
      initially self-identify as depressed. Large effect sizes with significant
      improvements were found for depression severity and social adjustment; pain
      interference remained unchanged. Most enrolled patients reported a high level of
      satisfaction with IPT-P. This pilot study provides preliminary support for the
      use of IPT-P for patients with comorbid depression and chronic pain.

PMID- 20699728
TI  - Effect of visual information on postural control in patients with schizophrenia.
AB  - Lateralized motor and attentional abnormalities contribute to schizophrenia, but
      little is known about possible abnormalities in neural machinery involved in
      postural control. We examined postural stability of 22 patients with
      schizophrenia taking medication and 14 healthy control participants using
      computerized force platform posturography. The shift in the center point of
      pressure in the condition of eyes open versus eyes closed characterizes the
      effect of visual information on body posture. Closing the eyes had less of an
      effect on the center point of velocity (velocity sm/s) in the patients with
      schizophrenia than in the control group (median change, 36% vs. 70%, p = 0.0006).
      Change in the body position during eye closure tended to be directed rightwards
      in the control group but leftwards in the group with schizophrenia (p = 0.025).
      The results show that visual component had less dominance in the balance control
      of these patients with schizophrenia. The lateralized effect of visual
      information on posture was also impaired.

PMID- 20699729
TI  - Evidence for significant improvement in prediction of acute risk for suicidal
      behavior.

PMID- 20699730
TI  - No evidence for improvement in the accuracy of suicide risk assessment.

PMID- 20699731
TI  - Delaware's inclusive trauma system: impact on mortality.
AB  - BACKGROUND: The impact of implementing an inclusive state trauma system on injury
      related mortality for patients with life-threatening injuries was assessed.
      METHODS: Using the state trauma registry, trauma patients evaluated in all of
      Delaware's acute care hospitals from 1998 to 2007 were identified. Patients were
      categorized by injury severity score (ISS) groups (1-9, 10-15, 16-24, and >24).
      Each category was analyzed by mortality and interfacility transfer rate to the
      Level I trauma center for each year. An analysis of the National Trauma Data Bank
      (NTDB) for these ISS groups and mortality was performed to provide a comparative
      benchmark. Chi(2) and analysis of variance were used where appropriate (p <or=
      0.05). RESULTS: A total of 40,063 entries were identified within the state trauma
      registry for the 10-year study period. Mortality rates did not significantly
      differ for ISS categories except for ISS >24 group. For this group, there was an
      incremental mortality decrease from 45.7% (1998) to 20.5% (2007) (p <or= 0.0005).
      This rate of decrease in mortality was significantly greater than that displayed
      in the NTDB. The rate for the aggregate of all interfacility transfers and ISS
      >24 group managed at the Level I hospital significantly increased over the same
      period. CONCLUSION: Since its inception, Delaware's trauma system, in which all
      acute care hospitals participate, has been associated with an incremental,
      significant decrease in mortality of the most critically injured patients. This
      decrease is more substantial than that experienced nationally as depicted within
      the NTDB. These findings and our evolving experience support the concept and
      benefits of an "inclusive" trauma system.

PMID- 20699732
TI  - Inefficiencies in a rural trauma system: the burden of repeat imaging in
      interfacility transfers.
AB  - BACKGROUND: Local hospitals (LHs) transferring patients to regional trauma
      centers (TCs) often obtain CT scans to diagnose injuries and justify transfer.
      However, these imaging studies are often repeated at the receiving TCs. This
      study was performed to examine how frequently computed tomography (CT) scans were
      repeated in interfacility transfers in a rural trauma system and to identify the
      most common reason for repeating the studies. METHODS: Patients transferred to a
      rural Level I TC from October 2007 through February 2008 were prospectively
      evaluated. Data abstracted included CT scans performed at LHs and CT scans
      repeated at the TC. Additionally, the reason for repeating each study was
      recorded as follows: (1) scan not sent, (2) software not compatible, (3)
      inadequate technique (no intravenous contrast), (4) inadequate technique (no
      reconstructions), and (5) clinically indicated. RESULTS: During the study period,
      138 patients were transferred to the TC. Of these, 104 (75%) underwent CT imaging
      before transfer. Sixty of these patients (58%) underwent repeat CT imaging at the
      TC. Overall, 98 of 243 (40%) scans were repeated. Head CT scans were repeated
      predominantly because of clinical indications. All other body region CT scans
      were repeated predominantly because of inadequate technique at the LHs.
      CONCLUSIONS: CT scans were repeated in 58% of interfacility transfers. Repeat CT
      scans inevitably result in increased radiation exposure to patients as well as
      additional charges and may be an important patient safety and cost issue for
      trauma systems.

PMID- 20699733
TI  - Applying composite performance measures to trauma care.
AB  - BACKGROUND: To investigate the association between a number of hospital level
      composite index methodologies developed from trauma indicators with inhospital
      mortality. METHODS: Data from January 2001 to December 2006 were extracted from
      the Victorian State Trauma Registry (Australia) and the Trauma Audit and Research
      Network (United Kingdom). Three composite methods were explored, including two
      denominator-based weight approaches and a factor analysis technique. The
      association between the composite measures and the count of inhospital mortality
      was investigated using Poisson regression models adjusting for expected deaths
      per hospital using the Trauma Injury Severity Score methodology. RESULTS:
      Composite scores were calculated per hospital, per year. The composite score was
      entered in statistical models as a raw score, and the mortality difference across
      the central 50% of the composite index was ascertained. In total, 9,218 patients
      were included and were distributed across 14 hospitals. Composite scores
      demonstrated an inverse relationship with risk-adjusted inhospital mortality.
      From the 25th to the 75th percentile of each composite, mortality decreased by
      11.99%, 13.58%, and 16.13% (p < 0.05). CONCLUSION: Trauma composite indices
      demonstrate construct validity when used as measures of hospital level process
      and represent potentially useful methods of analyzing and reporting quality
      indicators.

PMID- 20699734
TI  - Trauma center designation correlates with functional independence after severe
      but not moderate traumatic brain injury.
AB  - BACKGROUND: The mortality of traumatic brain injury (TBI) continues to decline,
      emphasizing functional outcomes. Trauma center designation has been linked to
      survival after TBI, but the impact on functional outcomes is unclear. The
      objective was to determine whether trauma center designation influenced
      functional outcomes after moderate and severe TBI. METHODS: Trauma subjects
      presenting to an American College of Surgeons (ACS) Level I or II trauma center
      with a Glasgow Coma Score (GCS) <or=12 who survived to discharge were identified
      using the National Trauma Databank (2002-2006). Outcomes were functional
      independence (FI) defined as a modified functional independence measure (FIM) of
      12, and independent expression (IE) defined as a FIM component of 4. These were
      compared between Level I and Level II centers in subjects with both moderate (GCS
      9-12) and severe (GCS <or=8) TBI using stepwise logistic regression to adjust for
      demographics, injuries, and comorbidities. RESULTS: Analysis identified 25,170
      subjects (72% severe TBI). After adjusting for covariates, ACS Level I
      designation was associated with FI (odds ratio: 1.16; confidence interval: 1.07
      1.24, p < 0.01) and IE (1.10; 1.03-1.17, p < 0.01) after severe TBI. Trauma
      center designation was not associated with FI or IE after moderate TBI.
      CONCLUSIONS: ACS trauma center designation is significantly associated with FI
      and IE after severe, but not moderate TBI. Prospective study is warranted to
      verify and explore factors contributing to this discrepancy.

PMID- 20699735
TI  - Cranioplasty after postinjury decompressive craniectomy: is timing of the
      essence?
AB  - BACKGROUND: The appropriate timing of cranioplasty after decompressive
      craniectomy for trauma is unknown. Potential benefits of delayed intervention (>6
      weeks) for reducing the risk of infection must be balanced by persistent altered
      cerebrospinal fluid dynamics leading to hydrocephalus. We reviewed our recent 5
      year experience in an effort to improve patient throughput and develop a rational
      decision making plan. METHODS: A 5-year query (2003-2007) of our level I
      neurotrauma database. From 2,400 head injuries, we performed a total of 350
      craniotomies. Of the 350 patients who underwent craniotomy for trauma, 70
      patients (20%) underwent decompressive craniectomy requiring cranioplasty. Timing
      of cranioplasty, cranioplasty material, postoperative infections, and incidence
      of hydrocephalus were evaluated with logistic regression to study potential
      associations between complications and timing, adjusted for risk factors.
      RESULTS: No specific time frame was predictive of hydrocephalus or infection, and
      logistic regression failed to identify significant predictors among the collected
      variables. CONCLUSION: In our experience, the prior practice of delayed
      cranioplasty (3-6 months postdecompressive craniectomy), requiring repeat
      hospital admission, does not seem to lower postcranioplasty infection rates nor
      the need for cerebrospinal fluid diversion procedures. Our current practice
      emphasizes cranioplasty during the initial hospital admission, as soon as there
      is resolution on computed tomography scan of brain swelling outside of the
      cranial vault with concurrent clinical examination. This occurs as early as 2
      weeks postcraniectomy and should lower the overall cost of care by eliminating
      the need for additional hospital admissions.

PMID- 20699736
TI  - Pentobarbital coma for refractory intra-cranial hypertension after severe
      traumatic brain injury: mortality predictions and one-year outcomes in 55
      patients.
AB  - OBJECTIVE: To identify predictors of mortality and long-term outcomes in
      survivors after pentobarbital coma (PBC) in patients failing current treatment
      standards for severe traumatic brain injuries (TBI). This is a retrospective
      cohort study of severe TBI patients receiving PBC at Level I Trauma Center and
      tertiary university hospital. METHODS: Four thousand nine hundred thirty-four
      patients were admitted to the trauma intensive care unit with severe TBI (head
      Abbreviated Injury Scale >or= 3) between April 1998 and December 2004. Six
      hundred eleven received intracranial pressure (ICP) monitoring and 58 received
      PBC. Three patients underwent craniotomy for intracranial mass lesion and were
      excluded. The study group received standardized medical management for severe TBI
      including opiates, benzodiazepines, elevation of the head of bed, avoidance of
      hypotension and hypercapnia and hyperosmolar therapy (HOsmRx). In addition, 31 of
      55 patients (56%) underwent placement of intraventricular catheters for
      cerebrospinal fluid drainage. If routine medical management and cerebrospinal
      fluid diversion failed to control ICP, then the patient was determined to have
      refractory intracranial hypertension (RICH) and PBC treatment was initiated. PBC
      was performed with pentobarbital infusion with continuous electroencephalogram
      monitoring to ensure adequate burst suppression. The measurements include serum
      sodium (Na) and osmolality (Osm) were assessed as indicators for initiation of
      PBC and to estimate the 50% mortality cut-points when controlling for ICP. Follow
      up functional outcomes were assessed using the Glasgow Outcome Scale and
      stratified according to admission Glasgow Coma Scale score and Marshall computed
      tomography classification. Of the 55 PBC patients, 22 (40%) survived at
      discharge. 19 of 22 had long-term follow-up (1 year or more) available. Of these,
      13 (68%) were normal or functionally independent (Glasgow Outcome Scale score 4
      or 5). Serum Na and Osm were associated with death (p < 0.05) when controlling
      for ICP. The 50% mortality cut-points were Na of 160 mEq/L and Osm of 330 mOsm/kg
      H2O. Median minimum cerebral perfusion pressure after PBC was 42 mm Hg in
      survivors and 34 mm Hg in nonsurvivors (p = 0.013). CONCLUSIONS: In patients with
      severe TBI and RICH, survival at discharge of 40% with good functional outcomes
      in 68% of survivors at 1 year or more can be achieved with PBC after failure of
      HOsmRx. Based on 50% mortality cut-points, analysis suggests the limits of HOsmRx
      to be Na of 160 mEq/L and Osm of 330 mOsm/Kg H2O. Maintenance of higher cerebral
      perfusion pressure after PBC is associated with survival. PBC treatment of RIH
      may be even more important when other treatments of RIH, such as decompressive
      craniectomy, are not available.

PMID- 20699737
TI  - Prehospital airway and ventilation management: a trauma score and injury severity
      score-based analysis.
AB  - BACKGROUND: Emergent endotracheal intubation (ETI) is considered the standard of
      care for patients with severe traumatic brain injury (TBI). However, recent
      evidence suggests that the procedure may be associated with increased mortality,
      possibly reflecting inadequate training, suboptimal patient selection, or
      inappropriate ventilation. OBJECTIVE: To explore prehospital ETI in patients with
      severe TBI using a novel application of Trauma Score and Injury Severity Score
      methodology. METHODS: Patients with moderate-to-severe TBI (head Abbreviated
      Injury Scale score 3+) were identified from our county trauma registry.
      Demographic information, pre-resuscitation vital signs, and injury severity
      scores were used to calculate a probability of survival for each patient. The
      relationship between outcome and prehospital ETI, provider type (air vs. ground),
      and ventilation status were explored using observed survival-predicted survival
      and the ratio of unexpected survivors/deaths. RESULTS: A total of 11,000 patients
      were identified with complete data for this analysis. Observed and predicted
      survivals were similar for both intubated and nonintubated patients. The ratio of
      unexpected survivors/deaths increased and observed survival exceeded predicted
      survival for intubated patients with lower predicted survival values. Both
      intubated and nonintubated patients transported by air medical crews had better
      outcomes than those transported by ground. Both hypo- and hypercapnia were
      associated with worse outcomes in intubated but not in nonintubated patients.
      CONCLUSIONS: Prehospital intubation seems to improve outcomes in more critically
      injured TBI patients. Air medical outcomes are better than predicted for both
      intubated and nonintubated TBI patients. Iatrogenic hyper- and hypoventilations
      are associated with worse outcomes.

PMID- 20699738
TI  - Smoking in trauma patients: the effects on the incidence of sepsis, respiratory
      failure, organ failure, and mortality.
AB  - BACKGROUND: There is a high percentage of smokers among trauma patients.
      Cigarette smoking has been associated with the development of acute lung injury
      and the adult respiratory distress syndrome in critically ill patients. It is
      also known that nicotine exerts immunosuppressive and anti-inflammatory effects
      with chronic use. Trauma patients who are smokers usually go through acute
      nicotine withdrawal after the traumatic event and during their stay in ICU. How
      the smoking status and acute nicotine withdrawal affect outcomes after trauma is
      unknown. This question was addressed in this study by analyzing the incidence of
      sepsis, septic shock and multiple organ dysfunction syndrome, and other outcomes
      in smoking and nonsmoking trauma patients. METHODS: A retrospective cohort of
      trauma patients who met the criteria was randomly selected from the trauma
      registry. Individual charts were reviewed to confirm documented smoking status.
      Criteria for selection included the following: Injury Severity Score >or=20, age
      18 to 65 years, hospital length of stay >72 hours. Patients with COPD/emphysema,
      diabetes mellitus, cardiac disease, malignancy, pregnancy, or steroid use were
      excluded. RESULTS: Overall, 327 patient charts were reviewed: 156 smokers and 171
      nonsmokers. Men outnumbered women in the smoking group fourfold (p = 0.003 versus
      nonsmokers). Age, Injury Severity Score, the presence of shock on admission, the
      type of trauma (blunt or penetrating), ICU and hospital length of stay, and the
      duration of ventilator support were similar between smokers and nonsmokers. There
      were no differences in the incidence of sepsis, pneumonia, adult respiratory
      distress syndrome, or multiple organ dysfunction syndrome. Mortality was low
      (1.2% in smokers; 0.6% in nonsmokers) and did not differ significantly between
      the groups. CONCLUSIONS: The smoking status plays a minimal role in the outcome
      of healthy trauma patients. This suggests that the acute nicotine withdrawal that
      usually occurs in critically ill patients has no clinically significant
      implications after injury.

PMID- 20699739
TI  - What is the safety of nonemergent operative procedures performed at night? A
      study of 10,426 operations at an academic tertiary care hospital using the
      American College of Surgeons national surgical quality program improvement
      database.
AB  - BACKGROUND: Ever-increasing numbers of in-house acute care surgeons and
      competition for operating room time during normal daytime business hours have led
      to an increased frequency of nonemergent general and vascular surgery procedures
      occurring at night when there are fewer residents, consultants, nurses, and
      support staff available for assistance. This investigation tests the hypothesis
      that patients undergoing such procedures after hours are at increased risk for
      postoperative morbidity and mortality. METHODS: Clinical data for 10,426
      operative procedures performed over a 5-year period at a single academic tertiary
      care hospital were obtained from the American College of Surgeons National
      Surgical Quality Improvement Program Database. The prevalence of preoperative
      comorbid conditions, postoperative length of stay, morbidity, and mortality was
      compared between two cohorts of patients: one who underwent nonemergent operative
      procedures at night and other who underwent similar procedures during the day.
      Subsequent statistical comparisons utilized chi tests for comparisons of
      categorical variables and F-tests for continuous variables. RESULTS: Patients
      undergoing procedures at night had a greater prevalence of serious preoperative
      comorbid conditions. Procedure complexity as measured by relative value unit did
      not differ between groups, but length of stay was longer after night procedures
      (7.8 days vs. 4.3 days, p < 0.0001). CONCLUSIONS: Patients undergoing nonemergent
      general and vascular surgery procedures at night in an academic medical center do
      not seem to be at increased risk for postoperative morbidity or mortality.
      Performing nonemergent procedures at night seems to be a safe solution for
      daytime overcrowding of operating rooms.

PMID- 20699740
TI  - Packed red blood cells suppress T-cell proliferation through a process involving
      cell-cell contact.
AB  - BACKGROUND: Packed red blood cell (PRBC) transfusion suppresses immunity and
      increases morbidity and mortality. Leukocyte reduction has failed to abrogate
      these effects, thus implicating red blood cells themselves or their components.
      PRBC impair proliferation of immortal (Jurkat) T cells by depleting arginine from
      the extracellular environment. The effect of PRBC on isolated ex vivo T-cell
      proliferation has not been reported. We hypothesize that PRBCs depress mitogen
      stimulated proliferation in isolated human and mouse T cells. METHODS: Human
      peripheral T cells were isolated by Ficoll-Hypaque gradient, purified by magnetic
      separation, and stimulated with anti-CD3 or anti-CD28. DO11.10 transgenic mouse
      splenic T cells were stimulated with ovalbumin. Cells were cultured at 1 x
      10(6)/mL in 96-well plates or in 24-transwell plates in the presence of PRBC
      (0.015-5% by volume, stored for 4-6 weeks). In culture media, arginine and
      citrulline were varied. Proliferation was measured at 72 hours by thymidine
      incorporation. T-cell viability, apoptosis, and receptor zeta chain were measured
      by flow cytometry. RESULTS: PRBC significantly depressed human peripheral and
      mouse splenic T-cell proliferation in a dose-dependent manner. PRBC arginase
      blockade by N-omega-hydroxy-nor-l-arginine only partly restored proliferation.
      Cell contact was required in both cell types for maximal effect. Depressed zeta
      chain in human peripheral T cells was partly restored by arginase blockade.
      Salvage by high-dose arginine and citrulline was unsuccessful. Decreased
      proliferation was not related to cell death. CONCLUSION: PRBC suppresses mitogen
      stimulated human and antigen-stimulated mouse T-cell proliferation by mechanisms
      independent of arginine depletion. This is a novel mechanism for transfusion
      associated immune suppression.

PMID- 20699741
TI  - Prestorage leukoreduction ameliorates the effects of aging on banked blood.
AB  - BACKGROUND: Previous studies have demonstrated that the transfusion of older
      blood is independently associated with higher rates of infectious complications,
      multiple organ failure, and mortality. Putative mechanisms implicate leukocytes
      in stored blood that generate immunomodulatory mediators as the stored blood
      ages. The purpose of this retrospective cohort study was to describe the effect
      of prestorage leukoreduction (PS-LR) on the detrimental clinical effects of
      increasing age on blood products used in trauma patients. METHODS: All patients
      receiving >or=6 units of packed red cells and surviving >or=48 hours since May
      1999 when institutional universal PS-LR was begun were identified. Transfusion
      requirements, demographic data, and causes of death were collected. Blood bank
      records were reviewed to determine the age of each unit of blood transfused.
      Multivariate logistic regression was used to determine the relationship between
      the age of PS-LR transfused blood and mortality after adjusting for total
      transfusion requirement, patient age, Injury Severity Score, head Abbreviated
      Injury Score, mechanism of injury, and gender. A subgroup analysis was performed
      excluding those patients in whom care was withdrawn at 48 hours to 72 hours
      postinjury for brain death or neurologic devastation. RESULTS: A total of 399
      patients, receiving 6,603 units of blood, met inclusion criteria. Mortality
      analysis showed that increasing Injury Severity Score, patient age, head
      Abbreviated Injury Score, and number of units of packed red cells transfused were
      all independently associated with an increased risk of death. When mean age of
      blood was analyzed as a continuous variable, a significant reduction in the risk
      of death with increasing mean age of transfused PS-LR blood was noted (odds ratio
      [OR], 0.959; 95% confidence interval [CI], 0.924-0.996). Both of these findings
      persisted when the mean age of blood was dichotomized at 14 days (OR, 0.426; 95%
      CI, 0.182-0.998) and 21 days (OR, 0.439; 95% CI, 0.225-0.857). The area under the
      curve for the receiver operating characteristics of our mortality model was 0.90.
      After excluding 13 patients in whom care was withdrawn 48 hours to 72 hours
      postinjury for brain death or neurologic devastation, the mortality analysis
      still showed that increasing injury severity, number of units of packed red cells
      transfused, and age were all independently associated with an increased risk of
      death. The protective effect of receiving older blood seen in the all-cause
      mortality analysis disappeared because no association was found between odds of
      dying and increasing age of packed red blood cells units transfused. This was
      true whether the mean age of transfused blood was dichotomized at 14 days (OR,
      0.93; CI, 0.30-2.83) or at 21 days (OR, 0.54; CI, 0.25-1.16). CONCLUSION: Our
      data suggest that the deleterious effects of aging on banked blood are
      ameliorated by PS-LR. We are currently conducting a prospective observational
      study in an effort to duplicate the findings of this retrospective investigation.

PMID- 20699742
TI  - Hematopoietic progenitor cell mobilization is mediated through beta-2 and beta-3
      receptors after injury.
AB  - BACKGROUND: Hematopoietic progenitor cells (HPCs) are mobilized into the
      peripheral blood (PB) and then sequestered in injured tissue after trauma.
      Nonselective beta-adrenergic blockade (BB) has been shown to cause a decrease in
      mobilization of HPCs to the periphery and to injured tissue. Given the vast
      physiologic effects of nonselective BB, the aim of this study is to delineate the
      role of selective BB in HPC growth and mobilization. METHODS: Rats underwent
      daily intraperitoneal injections of propranolol (Prop), atenolol (B1), butoxamine
      (B2), or SR59230A (B3) for 3 days to induce BB. All groups then underwent lung
      contusion (LC). HPC presence was assessed by GEMM, BFU-E, and CFU-E colony growth
      both in injured lung and bone marrow (BM). Flow cytometry, using c-kit and CD71,
      was used to determine mobilization into PB. RESULTS: LC alone decreased BM HPC
      growth in all erythroid cell types and increased their number in injured lung
      (all *p < 0.05). beta-Blockade with Prop, B2, and B3 blockades restored BM HPC
      growth to control levels and decreased HPCs recovered in the injured lung.
      Similarly, Prop, B2, and B3 blockade prevented HPC mobilization to PB. B1
      blockade with atenolol had no impact on HPC growth and mobilization following LC.
      CONCLUSIONS: Nonselective BB reduced suppression of HPC growth in BM after injury
      and prevented the mobilization and subsequent sequestration of HPCs in injured
      tissue. Our data have shown that this effect is mediated through the B2 and B3
      receptors. Therefore, after trauma, treatment with selective B2 or B3 blocker may
      attenuate the BM suppression associated with tissue injury.

PMID- 20699743
TI  - Global differences in causes, management, and survival after severe trauma: the
      recombinant activated factor VII phase 3 trauma trial.
AB  - BACKGROUND: Little is known about international variation in mortality after
      severe trauma. This study examines variation in mortality, injury severity, and
      case management among countries from a recent prospective multinational trauma
      trial. METHODS: This trauma trial was a prospective, randomized, double-blinded,
      multicenter comparison of recombinant activated factor VII versus placebo in
      severely injured bleeding trauma patients. Differences in baseline patient
      characteristics, case management, and clinical outcomes were examined for the 11
      countries recruiting most patients. Between-country differences in mortality were
      examined using regression analysis adjusting for case mix and case management
      differences. Global predictors of mortality were also identified using
      multivariate regression analysis. RESULTS: Significant differences were observed
      between countries in unadjusted mortality rates at 24 hours (p = 0.025) and 90
      days (p < 0.0001). When adjusting for differences in case mix and case
      management, the between country differences in mortality at 24 hours and 90 days
      remained significant. Consistent independent predictors of 24-hour, 24-hour to 90
      day, and 90-day mortality were admission lactate >or=5 mmol/L (odds ratio: 9.06,
      3.56, and 5.39, respectively) and adherence to clinical management guidelines
      (odds ratio: 4.92, 5.90, and 3.26, respectively). On average, the damage control
      surgery guideline was less well adhered to than the RBC transfusion and
      ventilator guidelines. There was statistically significant variation between
      countries with respect to adherence to the RBC transfusion guideline.
      CONCLUSIONS: Considering international variation in mortality when designing or
      interpreting results from multinational trauma studies is important. Significant
      differences in mortality persisted between patients from different countries
      after case mix and case management adjustment. Adherence to clinical guidelines
      was associated with improved survival. Stratification, case mix adjustment, and
      use of guidelines on damage control surgery, transfusion, and ventilation may
      mitigate country-driven variation in mortality.

PMID- 20699744
TI  - Use of recombinant factor VIIa in US military casualties for a five-year period.
AB  - BACKGROUND: Two prospective randomized trauma trials have shown recombinant
      factor VIIa (rFVIIa) to be safe and to decrease transfusion requirements. rFVIIa
      is presently used in 22% of massively transfused civilian trauma patients. The US
      Military has used rFVIIa in combat trauma patients for five years, and two small
      studies of massively transfused patients described an association with improved
      outcomes. This study was undertaken to assess how deployed physicians are using
      rFVIIa and its impact on casualty outcomes. METHODS: US combat casualties (n =
      2,050) receiving any blood transfusion from 2003 to 2009 were reviewed to compare
      patients receiving rFVIIa (n = 506) with those who did not (n = 1,544).
      Propensity-score matching (primary analysis) and multivariable logistic
      regression were used to compare outcomes. Differences were determined at p <
      0.05. RESULTS: Twenty-five percent of patients received rFVIIa. Significant
      differences were noted between groups in indices of injury severity (Injury
      Severity Score, Abbreviated Injury Scale score, and Glasgow Coma Scale score),
      admission physiology (systolic blood pressure, diastolic blood pressure, heart
      rate, temperature, base deficit, hemoglobin, and international normalization
      ratio), and use of blood products, indicating that patients treated with rFVIIa
      were more severely injured, in shock, and coagulopathic. For propensity-score
      matching, factors associated with death were used: Injury Severity Score, Glasgow
      Coma Scale score, heart rate, systolic blood pressure, diastolic blood pressure,
      Hgb, and total packed red blood cell. A total of 266 patients per group were
      matched; 52% of the rFVIIa group. After pairing, there were no significant
      differences in any of the demographics, including incidence of massive
      transfusion (53% vs. 51%). There was no difference in the rate of complications
      (21% vs. 21%) or mortality (14% vs. 20%) for patients not treated or receiving
      rFVIIa, respectively. CONCLUSION: In military casualties, rFVIIa is used in the
      most severely injured patients based on physician selection rather than on
      guideline criteria. Use of rFVIIa is not associated with an improvement in
      survival or an increase in complications. The undetected bias of physician
      selection of patients for treatment with rFVIIa, likely, has an impact on case
      matching to achieve equivalence similar to that of randomized control studies.
      This inability to match populations, thus, prevents definitive interpretation of
      this study and others studies of similar design. This problem emphasizes the need
      to develop entry criteria to identify patients who could potentially benefit from
      use of rFVIIa and the need to subsequently perform efficacy studies.

PMID- 20699745
TI  - Reducing leukocyte trafficking preserves hepatic function after sepsis.
AB  - INTRODUCTION: Leukocyte trafficking may induce hepatic dysfunction in sepsis.
      Herein, we hypothesize that reduction in leukocyte adhesion and, hence, leukocyte
      endothelial interaction by activated protein C (aPC) may preserve hepatic
      function after sepsis. METHODS: Rats underwent sham or cecal ligation and
      puncture, followed by saline or aPC (1 mg/kg intravenously) infusion, twice daily
      for 4 days. Cytokine levels were determined by enzyme-linked immunosorbent assay.
      Liver function and injury were assessed by bile production and plasma aspartate
      transaminase, respectively. In parallel experiments, neutrophils were labeled
      with Rhodamine 6G, and trafficking determined by cell motion tracking using
      intravital microscopy. Leukocyte trafficking and traveling velocity were computed
      at baseline and at 10 minutes and 40 minutes after endothelin-1 infusion.
      RESULTS: Sepsis induced 90% mortality and elevated levels of interleukin (IL)-2
      (167 pg/mL +/- 39 pg/mL vs. 68 pg/mL +/- 2 pg/mL, p < 0.05), IL-6 (5,806 pg/mL +/
      3,389 pg/mL vs. 0 pg/mL +/- 0 pg/mL, p < 0.05), and IL-8 (492 pg/mL +/- 22 pg/mL
      vs. 21 pg/mL +/- 17 pg/mL, p < 0.05). Aspartate transaminase levels increased
      (227 IU/L +/- 14 IU/L vs. 51 IU/L +/- 7 IU/L, p < 0.05) in cecal ligation and
      puncture animals, whereas bile production decreased by fivefold compared with
      sham (436 microg/kg/h +/- 247 microg/kg/h vs. 2,357 microg/kg/h +/- 147
      microg/kg/h, p < 0.05). Hepatic leukocyte adhesion increased threefold in septic
      animals (42.7 WBC per image +/- 7.3 WBC per image vs. 14.8 WBC per image +/- 3.8
      WBC per image, p < 0.01), whereas leukocyte velocity decreased compared with sham
      (10.5 microm/s +/- 2.2 microm/s vs. 22.3 microm/s +/- 2.4 microm/s, p < 0.01). By
      contrast, aPC treatment reduced mortality to 60%, attenuated inflammatory
      cytokines, reduced leukocyte trafficking, and preserved hepatic function.
      CONCLUSIONS: Our data demonstrate that sepsis may, in part, induce hepatic
      dysfunction by augmenting leukocyte trafficking into hepatic sinusoids. Treatment
      with aPC attenuated leukocyte trafficking and, in doing so, preserved hepatic
      function and improved survival. Collectively, these data suggest an important
      role for protein C-dependent leukocyte-endothelial interaction in sepsis.

PMID- 20699746
TI  - Pulmonary injury risk assessment for long-duration blasts: a meta-analysis.
AB  - BACKGROUND: Long-duration blasts are an increasing threat with the expanded use
      of thermobaric and other novel explosives. Other potential long-duration threats
      include large explosions from improvised explosive devices, weapons caches, and
      other explosives including nuclear explosives. However, there are very few long
      duration pulmonary blast injury assessments, and use of short-duration exposure
      injury metrics is inappropriate as the injury mechanism for long-duration
      exposures is likely different from that of short-duration exposures. METHODS:
      This study develops an injury model for long-duration (>10 milliseconds positive
      overpressure phase) blasts with sharp rising overpressures. For this study, data
      on more than 2,730 large animal experiments were collected from more than 55
      experimental studies on blast. From this dataset, nearly 850 large animal
      experiments were selected with positive phase overpressure durations of 10
      milliseconds or more. Various models were evaluated to determine the best fit of
      injury risk as a function of pressure and duration. A linear logistic regression
      was performed on the experimental data for threshold injury and lethality in
      terms of pressure and duration. The effects of mass, pressure, and duration
      scaling were all evaluated, and two goodness-of-fit indicators were used to
      assess the different models. RESULTS AND CONCLUSIONS: New injury risk assessment
      curves were determined for both incident and reflected pressure conditions for
      reflecting surface and free-field exposures. Position dependent injury risk
      curves were also determined. The resulting curves are an improvement to existing
      assessments, because they use actual data to demonstrate theoretical assumptions
      on the injury risk.

PMID- 20699747
TI  - Cardiopulmonary effects of matching positive end-expiratory pressure to abdominal
      pressure in concomitant abdominal hypertension and acute lung injury.
AB  - BACKGROUND: To evaluate the cardiopulmonary effects of positive end-expiratory
      pressure (PEEP) equalization to intra-abdominal pressure (IAP) in an experimental
      model of intra-abdominal hypertension (IAH) and acute lung injury (ALI). METHODS:
      Eight anesthetized pigs were submitted to IAH of 20 mm Hg with a carbon dioxide
      insufflator for 30 minutes and then submitted to lung lavage with saline and
      Tween (2.5%). Pressure x volume curves of the respiratory system were performed
      by a low flow method during IAH and ALI, and PEEP was subsequently adjusted to 27
      cm . H2O for 30 minutes. RESULTS: IAH decreases pulmonary and respiratory system
      static compliances and increases airway resistance, alveolar-arterial oxygen
      gradient, and respiratory dead space. The presence of concomitant ALI exacerbates
      these findings. PEEP identical to AP moderately improved oxygenation and
      respiratory mechanics; however, an important decline in stroke index and right
      ventricle ejection fraction was observed. CONCLUSIONS: Simultaneous IAH and ALI
      produce important impairments in the respiratory physiology. PEEP equalization to
      AP may improve the respiratory performance, nevertheless with a secondary
      hemodynamic derangement.

PMID- 20699748
TI  - Vascular arginase contributes to arteriolar endothelial dysfunction in a rat
      model of hemorrhagic shock.
AB  - BACKGROUND: Hemorrhagic shock causes hypoperfusion of peripheral tissues and
      promotes endothelial dysfunction, which may lead to further tissue injury. Trauma
      increases extrahepatic activity of arginase, an enzyme which competes for l
      arginine with nitric oxide synthase, and plays a key role in the development of
      endothelial dysfunction during aging, hypertension, and diabetes. However, the
      role of arginase in hemorrhage-induced endothelial dysfunction has not been
      studied. This study tests the hypothesis that arginase inhibition improves
      endothelial function after hemorrhage. METHODS: Male Sprague-Dawley rats were
      implanted with indwelling arterial catheters for blood pressure measurements and
      blood removal. Awake animals were subjected to a 45% fixed volume controlled
      hemorrhage and blood pressure was monitored. Unbled rats served as controls.
      Skeletal muscle arterioles were isolated 24 hours after hemorrhage and cannulated
      in a pressure myograph system. To study endothelial function, arterioles were
      exposed to constant midpoint, but altered endpoint pressures, to establish graded
      levels of luminal flow and internal diameter was measured. RESULTS: Hemorrhage
      lowered mean arterial pressure that spontaneously recovered to 78% and 88% of
      baseline in 2 hours and 20 hours, respectively. Vascular arginase II and blood
      glucose levels were elevated, whereas hemoglobin and insulin levels were
      decreased 24 hours after blood loss. In posthemorrhage arterioles, flow-induced
      dilation was abolished. Acute in vitro treatment with an inhibitor of arginase, N
      hydroxy-nor-l-arginine, restored flow-induced dilation to unbled control levels.
      Similarly, the arginase and nitric oxide synthase substrate, l-arginine, but not
      the inactive isomer, d-arginine, restored flow-induced dilation. CONCLUSIONS:
      These results indicate that arginase contributes to endothelial dysfunction in
      resistance vessels after significant hemorrhage.

PMID- 20699749
TI  - Application of the chemokine CXCL12 expression plasmid restores wound healing to
      near normal in a diabetic mouse model.
AB  - BACKGROUND: CXCL12 is a chemokine involved in postinjury leukocyte chemotaxis,
      migration, and homing of stem cells. We hypothesized that by increasing the level
      of the chemokine CXCL12 in wounds of diabetic mice, we would increase stem cell
      recruitment to the wound and, thus, accelerate time to wound closure. METHODS:
      Eighteen Lepr db-/db- (B6.Cg-m +/+ Leprdb/J; Jackson Labs, Bar Harbor, ME) and
      their nondiabetic littermates were wounded and treated either with an empty
      plasmid or a plasmid containing the CXCL12 gene. Wounds were measured
      approximately every 5 days until they closed completely and were analyzed using
      planimetry. Wounds were harvested, and relative expression of CXCL12 mRNA was
      measured using an ABI Prism SDS 7000. To study stem cells affected by this, the
      plasmid's affect on stem cell recruitment, we used flow cytometry. RESULTS: The
      diabetic wounds contain a significantly decreased level of CXCL12 mRNA at day 7
      postwounding, and these wounds take 55 days to heal. Application of a CXCL12
      plasmid to diabetic wounds significantly increases CXCL12 mRNA at day 7, and
      these wounds heal in 23 days. CONCLUSIONS: Lack of CXCL12 in diabetic wounds
      contributes to delayed wound healing and can be reversed via single application
      of a CXCL12-containing plasmid.

PMID- 20699750
TI  - Risk of mortality: the relationship with associated injuries and fracture
      treatment methods in patients with unilateral or bilateral femoral shaft
      fractures.
AB  - BACKGROUND: The aim of the study was to determine the relative contributions to
      mortality of a unilateral or a bilateral femoral fracture in patients with or
      without injuries to other body regions. STUDY DESIGN: An observational cohort
      study of the prospectively recorded England and Wales Trauma Registry data
      (Trauma Audit Research Network) from 1989 to 2003. METHODS: Patients were divided
      into the following groups: UFi (isolated unilateral femur injury), BFi (isolated
      bilateral femur injury), and UFa and BFa, if an associated injury was present.
      Injury and treatment data were collected for each patient. Logistic regression
      data analysis was performed to determine variables that were associated with
      increased mortality. RESULTS: Patients in group BFa had an increased mortality
      rate (31.6% vs. 9.8%) than patients in isolated bilateral femur injury group.
      Group BFa patients had an increased number of associated injuries (80%) than
      group UFa patients. Bilateral fracture, even in isolation, significantly
      increased the odds of mortality by 3.07. Intramedullary nailing was the method of
      fracture fixation associated with the lowest patient mortality overall. When
      assessing patient mortality in the BFa group with an New Injury Severity Score of
      >40, seven other fracture fixation regimens were associated with a lower
      mortality. CONCLUSIONS: The increase in mortality with BFs is more closely
      associated with the presence of associated injuries and poor physiologic
      parameters than with the presence of the BF alone. The presence of BFs should
      alert the clinician to the very high likelihood (80%) of significant associated
      injuries in other body systems and their life-threatening potential. Damage
      control fixation options should be considered in the subgroup with a very high
      New Injury Severity Score.

PMID- 20699751
TI  - Effects of hybrid plating with locked and nonlocked screws on the strength of
      locked plating constructs in the osteoporotic diaphysis.
AB  - BACKGROUND: Hybrid plating (HP) may improve fixation strength of locked plating
      (LP) constructs by combining the use of locked and nonlocked screws within a bone
      segment. This biomechanical study evaluated whether a hybrid bridge plating
      construct provides greater fixation strength than an all-locked construct in the
      osteoporotic diaphysis. METHODS: LP and HP constructs were applied to a validated
      surrogate of the osteoporotic femoral diaphysis in a bridge plating
      configuration. In LP constructs, plates were applied with three locking screws on
      each side of the fracture gap and remained 1 mm elevated. In HP constructs,
      plates were applied with two conventional screws complemented by a single locked
      screw on each side of the fracture. Constructs were tested under dynamic loading
      to failure in bending, torsion, and axial loading to analyze construct strength
      and failure mechanism in each loading mode. RESULTS: Compared with the LP
      construct, the HP construct was 7% stronger in bending (p = 0.17), 42% stronger
      in torsion (p < 0.001), and 7% weaker in axial compression (p = 0.003). In
      bending, constructs failed by periprosthetic fracture. In torsion, LP constructs
      failed by screw breakage, and HP constructs failed by periprosthetic fracture or
      breakage of the locking screw. In axial compression, all constructs failed by
      screw migration. CONCLUSIONS: HP delivered similar bending strength and higher
      torsional strength than an all-locked bridge plating construct, while causing
      only a small decrease in axial strength. It may therefore provide an attractive
      alternative to an all-locked construct for plate fixation in the osteoporotic
      diaphysis.

PMID- 20699752
TI  - Repositioning osteotomy for intra-articular malunion of distal radius with
      radiocarpal and/or distal radioulnar joint subluxation.
AB  - BACKGROUND: Intra-articular malunion of the distal radius may be complicated with
      radiocarpal and radioulnar joint subluxation, which may result in joint stiffness
      and loss of function. Conventional corrective osteotomy emphasizes on the
      restoration of the articular step-off. However, little information is available
      concerning the restoration of a concentric functioning joint through osteotomy.
      METHODS: From 2002 to 2007, 12 patients with chronic intra-articular distal
      radius fractures were evaluated at an average follow-up of 33.6 months after
      repositioning osteotomy. The average time from initial injury to reconstructive
      operation was 11.3 months. The indication for osteotomy included dorsal or volar
      subluxation of the radiocarpal joint, distal radioulnar joint, or both in
      addition to articular incongruity. A preoperative computed tomography scan or
      rapid prototyping (RP) models were performed as part of the surgical planning.
      Operation was preceded by volar, dorsal, or both approaches. Repositioning
      osteotomy and internal fixation were also performed. Radiographic analysis and
      the Disability of Arm, Shoulder and Hand score were used for the outcome
      assessment. RESULTS: All osteotomy sites healed and all events of radiocarpal and
      radioulnar subluxation were corrected. The average correction was 13.8 degrees
      (palmar tilt of the radius) and 1.9 mm in ulnar variance. The mean Disability of
      Arm, Shoulder and Hand score improved from 64 to 18. DISCUSSION: Conventional
      corrective osteotomy via an extra-articular approach was favorably performed to
      correct an extra-articular malalignment or nascent intra-articular malunion.
      Problems of abnormal architecture after an intra-articular fracture of the radius
      are complicated with subluxation of carpus or distal radioulnar joint, which
      require repositioning via precise articular approach. Both reconstructed computed
      tomography images and rapid prototyping models are very useful tools in
      preoperative planning for intra-articular osteotomy. Simulated osteotomy and
      joint repositioning can be performed in solid models before commencement of
      actual operation. CONCLUSION: Repositioning osteotomy consistently restores joint
      alignment and achieves functional improvement either in cases of nascent simple
      malunion or complex intra-articular malunion.

PMID- 20699753
TI  - The study of plate-screw fixation in the posterior wall of acetabulum using
      computed tomography images.
AB  - OBJECTIVE: The article aims to delineate the width of posterior column, the
      thickness of posterior wall, and safe angles for screw placement in the posterior
      wall to avoid intraarticular screw penetration. METHODS: The computed tomography
      (CT) images of 32 cadaveric adult bony hemipelvic specimens were initially
      obtained for the purpose of the study. Each specimen was sectioned at 1-cm
      intervals, and each plane of the crosssection was perpendicular to the surface of
      posterior column. By analyzing the CT images postprocessed with multiplanar
      reconstruction, the width of posterior column, the thickness of posterior wall,
      and the modified safe angle for screw placement in the posterior wall were
      measured and recorded. To validate the data obtained from the cadaveric model,
      this method was applied on 30 adult volunteers. The corresponding data were
      recorded and compared with those acquired from the cadaveric bony hemipelvis. In
      efforts to approve the usefulness of this method in practice, we have performed
      screw insertions in another 10 acetabular specimens and two operative cases by
      using the data from analyzing the CT images. RESULTS: The width of posterior
      column, the thickness of posterior wall, and the safe angles for screw insertion
      in the posterior wall were measured and recorded in both specimens and
      volunteers. Comparison of the corresponding data was made between specimens and
      volunteers, and no significant difference was found in the same gender and side
      (p > 0.05). The corresponding width of posterior column, thickness of posterior
      wall, and safe angles for screw placement was found to be statistically different
      between males and females in both specimens and volunteers (p < 0.05). In
      specimens group, the safe angles for the entry points 0.5, 1.0, 1.5, 2.0, 2.5,
      and 3.0 cm medial to the lateral acetabular brim were 49.23 degrees +/- 11.54
      degrees, 42.48 degrees +/- 8.97 degrees, 29.53 degrees +/- 7.86 degrees, 23.68
      degrees +/- 6.20 degrees, 18.42 degrees +/- 5.41 degrees and 15.91 degrees +/-
      4.37 degrees in males and the corresponding angles for the entry points 0.5, 1.0,
      1.5, 2.0, and 2.5 cm medial to the lateral acetabular brim were 45.02 degrees +/-
      8.82 degree, 35.98 degrees +/- 7.60 degrees, 23.77 degrees +/- 6.29 degrees,
      19.96 degrees +/- 4.36 degrees, and 14.68 degrees +/- 3.48 degrees in females,
      respectively. CT images of 10 acetabular specimens and two cases with posterior
      wall fractures show all screws were inserted into the posterior wall without
      penetration into the joint space. CONCLUSIONS: The oblique multiplanar
      reconstruction images perpendicular to the surface of posterior column were
      selected to describe the safe angle for screw insertion into posterior wall,
      which can provide consistent results in both specimens and volunteers. The method
      can be applied in practice both on acetabular specimens and operative cases and
      is helpful to make individual perioperative planning for safer fixation of
      posterior wall fracture.

PMID- 20699754
TI  - Motion in the unstable cervical spine during hospital bed transfers.
AB  - BACKGROUND: Hospital bed transfers, moves to examination room, X-ray, hospital
      bed, and/or surgery, have the potential of causing harm to a patient with an
      unstable cervical spine. This study evaluated motion generated in an unstable
      segment of the cervical spine during hospital bed transfers. A secondary goal
      purpose was to assess reduction in cervical motion using three collars and a no
      collar condition. METHODS: Cervical spine instability was created at C5-C6 in
      cadavers. A repeated measures design was used to compare bed transfer techniques:
      manual transfer performed by six trained individuals and a transfer made by two
      people using the On3 lateral transfer device. Both techniques were tested under
      four collar conditions. Cervical spine motion was measured using an
      electromagnetic motion analysis device with sensors fixed to the anterior bodies
      of C5 and C6. RESULTS: No significant differences were observed between transfer
      techniques (flexion, [p = 0.325]; axial rotation [p = 0.590]; lateral bending [p
      = 0.112]). Nor were there significant differences among the three collars used
      (flexion [p = 0.462]; axial rotation [p = 0.434]; lateral bending [p = 0.250]).
      For all transfers, using no collar resulted in more motion than using a collar;
      but was not statistically significant. CONCLUSIONS: Bed transfers made with a
      lateral transfer device seem to be as safe as those made by the lift and slide
      manual transfer. None of the collars tested were significantly better at
      preventing cervical spine motion during a transfer, but each allowed less
      movement than no collar.

PMID- 20699755
TI  - A comparison of the diagnostic performances of visceral organ-targeted versus
      spine-targeted protocols for the evaluation of spinal fractures using sixteen
      channel multidetector row computed tomography: is additional spine-targeted
      computed tomography necessary to evaluate thoracolumbar spinal fractures in blunt
      trauma victims?
AB  - BACKGROUND: It remains to be determined whether spine-targeted computed
      tomography (thoracolumbar spine computed tomography [TLS-CT]) images and visceral
      organ-targeted CT (abdominopelvic [AP]-CT) images are comparable for the
      evaluation of thoracolumbar spinal fractures using 16-channel multidetector row
      CT. The elimination of an additional spine-targeted CT protocol would
      substantially reduce time, the storage burden, and potential patient radiation
      exposure. METHODS: A total of 420 vertebrae in 72 consecutive patients who
      underwent AP-CT to assess blunt traumatic injury and an additional CT examination
      using a TLS-CT protocol to evaluate spinal fractures were retrospectively
      evaluated. The AP-CT set (set A, reconstructed with using a wide display field of
      view [FOV] and a soft algorithm) and the TLS-CT set (set S, reconstructed using a
      narrow display FOV and a hard algorithm) were composed of axial plus reformatted
      sagittal or coronal images or both. Three radiologists independently reviewed all
      CT data retrospectively. Performances for detecting and typing fractures were
      compared by using areas under receiver operating characteristic curves and by
      determining concordance rates. RESULTS: The overall areas under the curves for
      sets S and A for fracture detection were 0.996 and 0.995, respectively; no
      significant difference was found between the two sets. Concordance rates for
      typing performance also showed no statistical significance between the two sets
      for any of the three observers. CONCLUSION: Sixteen-channel multidetector row CT
      images reconstructed using a soft algorithm and a wide display FOV that cover the
      entire abdomen using a visceral organ-targeted protocol with 1.5-mm collimation
      are sufficient for the evaluation of spine fractures in trauma patients, given
      that multiplanar-reformatted images are provided.

PMID- 20699756
TI  - The combination of an online organ and tissue registry with a public education
      campaign can increase the number of organs available for transplantation.
AB  - BACKGROUND: A persistent shortage of organs and inexhaustible waiting lists
      continue to result in many people dying while awaiting transplantation. On July
      1, 2006, the California Department of Motor Vehicles joined forces with
      California's Online Organ and Tissue Registry and launched a campaign to increase
      donation rates. This campaign included intense public and media education. The
      efficacy of such a campaign on donor demographics has not been studied. METHODS:
      Retrospective analysis was conducted of organ donor referrals and donations from
      all southern California hospitals covered by a regional organ procurement agency.
      Organ donor demographics from 2 years before (pretime: 2004-2005) and 2 years
      after (posttime: 2007-2008) were compared. RESULTS: Pretime included 6,112
      referrals, 1,548 potential donors with 696 actual donors. Posttime included 7,119
      referrals, 1,409 potential donors, and 699 actual donors. Consent for donation
      improved to 51.0% from 47.5% (p = 0.064), family decline decreased to 32.6% from
      44.1% (p < 0.0001), and conversion rates improved to 49.6% from 45.0% (p =
      0.011). Coroners also declined donation less frequently during posttime (1.8% vs.
      0.6%, p = 0.004). Extended criteria donors improved to 9.5% from 3.8% (p <
      0.0001), and donor after cardiac death improved to 3.0% from 1.4% (p = 0.002). A
      decrease in organs per donor was noted (3.57% vs. 3.14%, p < 0.0001) most likely
      because of the increase in extended criteria donors and donor after cardiac
      death. CONCLUSIONS: Public and media education significantly improved organ donor
      demographics. Although this study compares only 2 years before with 2 years after
      the donation campaign, the results are extremely favorable. Therefore, a public
      donation campaign and an organ donor registry are effective promotions that could
      help increase the number of organs available for transplantation.

PMID- 20699757
TI  - The flexible chain saw during the American Civil War.

PMID- 20699758
TI  - Three-step approach to the harvest of the fibula osteoseptocutaneous flap.
AB  - INTRODUCTION: The ability to reliably include a skin paddle with the fibula
      osteoseptocutaneous (OSC) flap is crucial both from the perspective soft tissue
      reconstruction and flap monitoring. In this study, we describe a three-step
      approach to the harvest of the fibula OSC flap that is reliable and versatile.
      METHODS AND MATERIALS: Step 1 starts by exploring the posterior crural septum
      from the anterior incision of the skin island with the aim being to identify the
      septocutaneous vessels that will supply the skin. Step 2 proceeds from the
      posterior aspect of the skin island. The septocutaneous vessel is traced to its
      origin, and the peroneal artery is detached from flexor hallucis longus that
      covers the posterior aspect of the artery. Finally, step 3 entails detaching all
      muscles attached to the fibula from anteriorly and can be expediently completed
      as vessels supplying the skin component have already been secured. RESULTS: This
      technique was used successfully in 52 flap harvests. Absent septal vessels was
      noted in 4% of cases. In both cases, musculocutaneous perforators arising from
      the soleus muscle was used to supply the skin component. In one case, the
      septocutaneous vessel was noted to arise from the posterior tibial artery. Flap
      harvest was successful in all cases. CONCLUSION: The three-step approach allowed
      us to reliably harvest the fibula OSC flap. We were able to visualize the anatomy
      clearly with this technique, and this has enabled us to detect anomalous anatomy
      early on in the dissection. These were successfully managed by using
      musculocutaneous perforators to the skin island that would normally be cut.

PMID- 20699759
TI  - Helpful maneuvers for controlling bleeding from operative or traumatic vascular
      injuries.

PMID- 20699760
TI  - Intermediate-term follow-up of patients treated with percutaneous embolization
      for grade 5 blunt renal trauma.
AB  - BACKGROUND: The short-term efficacy and safety of percutaneous embolization for
      the treatment of hemodynamically unstable patients with grade 5 renal injuries
      secondary to blunt trauma has been previously established; however, there has
      been no published intermediate-term follow-up. The purpose of this study is to
      report intermediate-term follow-up and complications for this treatment modality.
      METHODS: A retrospective study was performed to determine intermediate-term
      outcomes in an observational cohort of patients who underwent percutaneous
      embolization for the management of grade 5 blunt renal trauma. Demographic and
      perioperative data were obtained. Follow-up was performed via mail and/or phone
      questionnaires. RESULTS: Between October 2004 and July 2008, 10 hemodynamically
      unstable patients with grade 5 blunt renal trauma were treated with percutaneous
      embolization. Mean age of the cohort was 29 years (range, 5-50). Mean follow-up
      via phone and/or mail questionnaires was 2.7 years (1.5-5.1 years). One patient
      reported a new diagnosis of hypertension, which is well controlled by a single
      antihypertensive medication. There were no reported complications of refractory
      hypertension, altered renal function, new urolithiasis, chronic pain, urine leak,
      arteriovenous fistula, or pseudoaneurysm. No other procedures were required after
      the initial embolization for their renal trauma. CONCLUSIONS: Management of grade
      5 renal injuries with percutaneous embolization is safe and is not associated
      with intermediate-term adverse events.

PMID- 20699761
TI  - Training and certification in surgical critical care: a position paper by the
      Surgical Critical Care Program Directors Society.
AB  - Delivery of Surgical Critical Care in the United States is facing multiple
      challenges including increasing complexity of care, escalating costs, shortage of
      well-trained physicians, and controversies about appropriate training and
      credentialing methods. In this position paper, the Surgical Critical Care Program
      Directors Society discusses some of these important issues and suggests a number
      of possible solutions.

PMID- 20699762
TI  - Traumatic rupture of two giant hepatic hemangiomas--a case report.

PMID- 20699763
TI  - Traumatic rupture of bilateral huge renal angiomyolipomas in tuberous sclerosis
      complex.

PMID- 20699764
TI  - Small change, big impact: prevention of vole captive bolt device hand injuries.

PMID- 20699765
TI  - Re: heart period variability monitoring in trauma and hemorrhage.

PMID- 20699766
TI  - Mixed martial warts.

PMID- 20699769
TI  - A colleague's plea.

PMID- 20699770
TI  - Refinement, reliability, and validity of the segmental assessment of trunk
      control.
AB  - PURPOSE: The Segmental Assessment of Trunk Control (SATCo) provides a systematic
      method of assessing discrete levels of trunk control in children with motor
      disabilities. This study refined the assessment method and examined reliability
      and validity of the SATCo. METHODS: After refining guidelines, 102 video
      recordings of the SATCo were made of 8 infants with typical development followed
      longitudinally from 3 to 9 months of age and 24 children with neuromotor
      disability with a mean age of 10 years 4 months. Eight researchers independently
      scored recordings. RESULTS: Intraclass correlation coefficient values for
      interrater reliability were more than 0.84 and 0.98 across all data sets and all
      aspects of control. Tests of concurrent validity with the Alberta Infant Motor
      Scales resulted in coefficients ranging from 0.86 to 0.88. CONCLUSION: The SATCo
      is a reliable and valid measure allowing clinicians greater specificity in
      assessing trunk control.

PMID- 20699771
TI  - Refinement, reliability, and validity of the segmental assessment of trunk
      control.

PMID- 20699772
TI  - Severity and characteristics of developmental delay can be assessed using
      variability measures of sitting posture.
AB  - PURPOSE: We sought to identify measures of variability from sitting postural sway
      that are significantly different among infants who were developing typically,
      those who were developmentally delayed or hypotonic, and those who later on had a
      diagnosis of spastic or athetoid cerebral palsy. METHODS: Sixty-five infants were
      evaluated when they were just developing the ability to sit upright by assessing
      center of pressure (COP) data, using measures of both amount and temporal
      organization of COP variability. RESULTS: The results indicated that measures of
      variability of COP could discriminate between infants with developmental delay
      and infants with cerebral palsy and add to the description of sitting postural
      behavior. CONCLUSIONS: Our method of evaluating sitting postural control could be
      an objective tool to help describe distinctive features of motor delay in an
      individual infant and could lead in the design of selective therapeutic
      interventions for improving postural control of infants with motor delays.

PMID- 20699773
TI  - Severity and characteristics of developmental delay can be assessed using
      variability measures of sitting posture.

PMID- 20699774
TI  - Development of a challenge assessment tool for high-functioning children with an
      acquired brain injury.
AB  - PURPOSE: To develop a performance-based challenge assessment to evaluate gross
      motor abilities of high-functioning youth with an acquired brain injury (ABI).
      METHODS: Potential items were identified from the literature. A panel of 4 expert
      physical therapists selected items on the basis of 3 criteria: safety to test,
      feasibility to administer, and importance to perform. Item reduction was
      completed using ratings from a physical therapist web survey. The Acquired Brain
      Injury-Challenge Assessment (ABI-CA) was created and pilot tested with youth with
      an ABI. RESULTS: Seventy-eight items were identified and reduced to 47 items
      following expert panel discussion. Web-survey item reduction by 75 pediatric
      physical therapists yielded a 24-item ABI-CA that was administered to 6 youth
      with an ABI, aged 8 to 17 years. The ABI-CA mean score was 50.7/81.0 (SD = 17.4).
      CONCLUSION: The ABI-CA was feasible to administer and demonstrated gross motor
      activity challenges beyond the Gross Motor Function Measure. Response option
      refinement and measure validation are required prior to clinical/research use.

PMID- 20699775
TI  - Development of a challenge assessment tool for high-functioning children with an
      acquired brain injury.

PMID- 20699776
TI  - Clinimetric properties of the alberta infant motor scale in infants born preterm.
AB  - PURPOSE: The Alberta Infant Motor Scale (AIMS) is a standardized motor assessment
      for young infants. This study aimed to examine the reliability of the AIMS in a
      group of infants born at or before 29 weeks of gestation. METHODS: Fifty-nine
      infants born preterm were recruited. Two experienced pediatric physical
      therapists participated in this reliability study. Infants were assessed at 4, 8,
      12, and 18 months corrected age (CA). RESULTS: Intrarater reliability was high
      (intraclass correlation coefficient [ICC] > or =0.99). The ICC for interrater
      reliability varied from 0.85 to 0.97. The ICC was low at 4 and 18 months CA.
      CONCLUSIONS: The AIMS is reliable in evaluating motor development in infants born
      preterm. Clinicians should be cautious about using the AIMS in infants at very
      young ages and those approaching independent ambulation. Accurate placement of
      the window on a movement repertoire is crucial. Attention is required when using
      the AIMS in infants developing atypically.

PMID- 20699777
TI  - Clinimetric properties of the alberta infant motor scale in infants born preterm.

PMID- 20699778
TI  - Ankle strength and functional limitations in children and adolescents with type I
      osteogenesis imperfecta.
AB  - PURPOSE: To determine whether children with type I osteogenesis imperfecta (OI)
      exhibit ankle plantar flexor weakness and whether this correlates with physical
      function. METHODS: Twenty children and adolescents with type I OI and 20 age
      matched controls (age 6-18 years) participated in a single evaluation session.
      Data included strength assessment, Gillette Functional Assessment Questionnaire,
      Pediatric Outcome Data Collection Instrument (PODCI), and Faces Pain Scale
      Revised. RESULTS: Ankle plantar flexor weakness was evident in the OI group
      compared with the control group. Heel-rise strength correlated with ankle
      isometric plantar flexion strength. Limitations in PODCI subscales-sports and
      physical function and pain/comfort-are present in the OI group. CONCLUSION: Ankle
      plantar flexor weakness is present in children and adolescents with type I OI and
      correlates with function. Gillette Functional Assessment Questionnaire, PODCI,
      and strength assessment are valuable evaluation tools for children and
      adolescents with type I OI and can aid therapists in goal setting.

PMID- 20699779
TI  - Ankle strength and functional limitations in children and adolescents with type I
      osteogenesis imperfecta.

PMID- 20699780
TI  - Growing older with cerebral palsy: insiders' perspectives.
AB  - PURPOSE: Research has shown that adults with cerebral palsy (CP) lose functional
      abilities earlier than persons who are able-bodied. Because CP is a lifespan
      disability, developmental therapists should be aware of these changes. METHODS:
      We used descriptive phenomenology to understand the unique, lived experiences of
      adults growing older with CP. Data were gathered through in-depth, semistructured
      interviews. Open-ended questions asked what it was like to age with CP, how these
      experiences were understood, how strategies were used to cope with changes, and
      what are the meanings of these experiences. RESULTS: A theme, Awareness,
      Acceptance, and Action, emerged from the data analysis. Participants were aware
      that their bodies were deteriorating quicker than those of peers who are able
      bodied. They developed acceptance that hastened actions toward improving their
      quality of life. CONCLUSIONS: These findings provide insights for pediatric
      therapists who work with children with CP about what may be important to their
      clients as they grow older.

PMID- 20699781
TI  - A longitudinal study of outcome measures for children receiving early
      intervention services.
AB  - PURPOSE: The purpose of this study was to compare the Pediatric Evaluation of
      Disability Inventory (PEDI) and the Mullen Scales of Early Learning (MSEL) as
      measures of change in children who received early intervention services. METHODS:
      Thirty-four children were stratified into 2 groups according to the presence of
      gross motor delay. The PEDI and MSEL were administered 3 times: at an average age
      of 18, 31, and 53 months of age. Data were analyzed using a repeated-measures
      multivariate analysis of variance. RESULTS: The findings suggest that PEDI
      Functional Skills Scaled Scores were capable of measuring change in both groups
      of children. The standard scores on the PEDI Functional Skills Social Scale were
      found to be more sensitive to change than the MSEL Receptive and Expressive
      Language scores for children with motor delays. CONCLUSION: Using PEDI scaled
      scores may be an effective strategy for measuring change in children receiving
      early intervention services.

PMID- 20699782
TI  - A longitudinal study of outcome measures for children receiving early
      intervention services.

PMID- 20699783
TI  - The gross motor function classification system: an update on impact and clinical
      utility.
AB  - PURPOSE: To examine the impact and utility of the Gross Motor Function
      Classification System (GMFCS) for children with cerebral palsy (CP) in research
      and clinical settings through a scoping review of publications from July 2003 to
      December 2008. METHODS: An online literature search was performed to retrieve
      relevant abstracts for classification according to GMFCS use. RESULTS: There has
      been a steadily increasing use of the GMFCS over the previous decade. Ongoing
      research was identified on the GMFCS measurement properties, as well as its use
      in validation of other tools. Observational and experimental studies continued to
      be the primary use of the GMFCS. Some studies discussed the GMFCS in clinical
      practice with respect to examination and evaluation. CONCLUSIONS: The GMFCS is
      clearly established as a principal classification system for children with CP as
      demonstrated by excellent uptake in research; however, literature on its clinical
      use is emerging more slowly over time. More emphasis on the clinical utility of
      the GMFCS in the published literature would be helpful.

PMID- 20699784
TI  - The gross motor function classification system: an update on impact and clinical
      utility.

PMID- 20699785
TI  - Power mobility and socialization in preschool: a case study of a child with
      cerebral palsy.
AB  - PURPOSE: Power mobility training for young children and infants appears feasible
      under controlled conditions. Dynamic, natural environments provide the ultimate
      test of training. The purpose of this case study was to determine whether it was
      feasible for Will, a 3-year-old boy with cerebral palsy, to use a power mobility
      device (UD2) in his preschool classroom and to quantify his classroom mobility
      and socialization. METHODS: Will, 2 peers (typically developing), and 2 teachers
      were filmed daily in class during a baseline phase without UD2, followed by a
      mobility phase with UD2. We coded socialization and mobility measures from video
      recordings. RESULTS: Will was more mobile and interactive when driving UD2 than
      during the baseline phase; however, he remained notably less mobile and
      interactive than his peers. CONCLUSIONS: The use and assessment of power mobility
      in a preschool classroom appear feasible. Issues important to maximizing
      children's use of power mobility for classroom participation are discussed.

PMID- 20699786
TI  - Pain assessment and management in children with neurologic impairment: a survey
      of pediatric physical therapists.
AB  - PURPOSE: This study explored pain assessment measures and interventions used by
      physical therapists in the treatment of children with neurologic impairment.
      METHODS: Following extensive literature review on pain assessment and
      intervention, a survey was developed, pilot tested, and posted on the listserv of
      the Pediatric Section of the American Physical Therapy Association. RESULTS:
      Eighty percent of the respondents used subjective measures to assess pain, 70%
      used self-report scales, and 41% used behavioral and physiological measures.
      Behaviors frequently used included vocalizations, facial expression, and
      irritability. Rarely used cues included decreased attention, withdrawal, and
      changes in sleeping and eating behaviors. Therapists used research-supported pain
      interventions such as distraction and praise as well as potentially harmful
      distress producing measures such as procedural talk and reassurance. CONCLUSION:
      Further research is needed to determine the feasibility of using behavioral pain
      assessment measures during physical therapy sessions. Physical therapist
      continuing education regarding nonpharmaceutical pain interventions is indicated.

PMID- 20699788
TI  - Abstracts of the 23rd Annual Meeting of the Transplantation Society. August 15
      19, 2010. Vancouver, British Columbia, Canada.

PMID- 20699787
TI  - Pain assessment and management in children with neurologic impairment: a survey
      of pediatric physical therapists.

PMID- 20700038
TI  - Expression of stem-cell markers (cytokeratin 15 and nestin) in primary adnexal
      neoplasms-clues to etiopathogenesis.
AB  - BACKGROUND: The overlap in histopathologic features and immunoprofile of eccrine
      and apocrine neoplasms confounds basic issues relating to lineage of these
      entities. METHODS: We evaluated expression of follicular stem-cell markers,
      cytokeratin (CK) 15 and nestin, in 78 benign and 23 malignant adnexal neoplasms.
      RESULTS: CK15 and nestin expression were noted in 39 of 78 (50%) and 36 of 78
      (46%) cases in the benign group, respectively (8 cutaneous mixed tumor, 10
      hidradenoma papilliferum, 9 apocrine cystadenoma, 11 cylindroma and/or
      spiradenoma, and 9 poroma/dermal duct tumor). CK15 and nestin expression were
      noted in 11 of 23 (48%) and 7 of 23 (30%) cases in the malignant group,
      respectively (6 microcystic adnexal carcinoma, 7 porocarcinoma, and 9 eccrine
      carcinoma). Except 1, both markers were negative in 4 syringocystadenoma
      papilliferum, 10 hidradenoma, 1 syringofibroadenoma, 10 syringoma, 1 eccrine
      adenoma, 8 poroma/dermal duct tumor, 5 eccrine hidrocystoma, and 1 apocrine
      carcinoma. CONCLUSIONS: Given that follicular germinative cells give rise to the
      folliculosebaceous apocrine unit, expression of CK15 and nestin in the majority
      of cutaneous mixed tumor, hidradenoma papilliferum, apocrine cystadenoma, and
      cylindroma/spiradenoma is suggestive of an apocrine origin/differentiation of
      these neoplasms. Reinforcing this and a novel finding of our study is the
      preferential expression of nestin in myoepithelial cells of these lesions.

PMID- 20700039
TI  - Statistical analysis of the concordance of immunohistochemical stains with the
      final diagnosis in spitzoid neoplasms.
AB  - INTRODUCTION: The classification of spitzoid melanocytic tumors can be difficult,
      and pathologists rely on both histological features and clinical information to
      arrive at a diagnosis. We proposed that an immunohistochemical panel could be
      useful in classifying these neoplasms and designed a study to test the
      independent contribution of the panel to the final diagnosis. METHODS: We
      identified 121 cases previously signed out either as (1) Spitz nevus, (2)
      atypical spitzoid neoplasm, favor Spitz nevus, (3) atypical spitzoid neoplasm of
      uncertain malignant potential, (4) atypical spitzoid neoplasm, favor melanoma,
      and (5) spitzoid melanoma. The slides were reveiwed in random order by 4
      pathologists. For the first review, the pathologists received only hematoxylin
      and eosin sections and patient age. Subsequently, the same pathologists
      interpreted the immunohistochemically stained slides (S-100A6, HMB-45, and MIB-1)
      on the same cases in randomized order without the benefit of either hematoxylin
      and eosin sections or patient age. The original diagnosis (based on a combination
      of clinical information, hematoxylin and eosin-stained sections and
      immunohistochemical stains) was the gold standard used for statistical analysis.
      The primary aim of the study was to determine the level of agreement between
      interpretions based on hematoxylin and eosin sections and age, the immunostains
      alone, and the gold standard, thus providing a measurement of the degree to which
      each of these elements contributes to the final diagnosis. The agreement between
      the gold standard and external review was also determined for those cases sent
      for external review. RESULTS: The generalized kappa statistic was 0.95 for both
      the hematoxylin and eosin-stained slides alone and the immunohistochemical stains
      alone, implying a high level of agreement among the 4 pathologists. The combined
      weighted kappa statistic for the comparison of hematoxylin and eosin sections and
      patient age to the gold standard was 0.49, and for the immunohistochemically
      stained slides to the gold standard 0.48, indicating that a diagnosis based on
      hematoxylin and eosin sections alone or immunostains alone show only a moderate
      and similar level of agreement with the gold standard diagnosis. Only the most
      controversial cases were sent for external review. The weighted kappa statistic
      estimate was 0.30 for the gold standard diagnosis on those cases and the external
      review. CONCLUSIONS: Spitzoid neoplasms remain a difficult area in
      dermatopathology and experts frequently disagree on the most challenging cases.
      An immunohistochemical panel contributes to the diagnosis of spitzoid tumors, and
      the contribution is statistically similar to that of hematoxylin and eosin
      sections and age. Interpretation remains subjective, as evidenced by the
      comparison of the gold standard and external review.

PMID- 20700040
TI  - Molluscum contagiosum virus infection in benign cutaneous epithelial cystic
      lesions-report of 2 cases with different pathogenesis?

PMID- 20700042
TI  - Novel oral anticoagulants: implications in the perioperative setting.
AB  - Patients undergoing surgery receive anticoagulation for perioperative
      thromboprophylaxis or ischemic cardiovascular disease. Because anticoagulants may
      also potentiate bleeding, clinicians need to understand the implications of
      anticoagulation in perioperative and postoperative patient management. Many newer
      anticoagulants that are now available or are in clinical development do not
      require routine coagulation monitoring, have more predictable dose responses, and
      have fewer interactions with other drugs and food. The most advanced oral
      anticoagulants in clinical development are the direct factor Xa inhibitors
      rivaroxaban and apixaban, and the direct thrombin inhibitor dabigatran etexilate.
      These agents have been evaluated in the postoperative setting in patients
      undergoing total hip- or knee-replacement surgery with promising results, and it
      remains to be seen whether these results will translate into other surgical
      settings. The impact of the new agents will be influenced by the balance between
      efficacy and safety, improved convenience, and potential cost-effectiveness
      benefits.

PMID- 20700041
TI  - Atypical fibroxanthoma with keloidal collagen.
AB  - Atypical fibroxanthoma (AFX) is a lesion that typically occurs on actinically
      damaged skin of the head and neck. Histopathology of these neoplasms reveals
      atypical cells, which often demonstrate positive staining for immunohistochemical
      markers such as vimentin and CD10. In the case reported, keloidal collagen was
      discovered on histopathology. To our knowledge, only rare reports in the
      literature describe an AFX with similar histopathologic findings, suggesting that
      this is a distinctive presentation of AFX.

PMID- 20700043
TI  - FK228 and oncogenic H-Ras synergistically induce Mek1/2 and Nox-1 to generate
      reactive oxygen species for differential cell death.
AB  - To investigate the mechanism behind the pro-apoptotic ability of oncogenic H-Ras
      to enhance FK228-induced apoptosis, we primarily used the 10T1/2-TR-H-Ras cell
      line, in which ectopic expression of oncogenic H-Ras(V12) is controlled by the
      addition of tetracycline into cultures, and secondarily used oncogenic H-Ras
      expressing MCF10A cells in our studies. Our results showed the pro-apoptotic
      roles of Mek1/2 activation, nicotinamide adenine dinucleotide phosphate-oxidase 1
      (Nox-1) elevation, and reactive oxygen species (ROS) production in FK228-induced
      selective cell death of oncogenic H-Ras-expressing cells versus counterpart
      cells. We found that although Nox-1 elevation and ROS production played essential
      roles in oncogenic H-Ras-induced cell proliferation and morphological
      transformation, the expression of oncogenic H-Ras and FK228 treatment
      synergistically induced activation of Mek1/2. This activation resulted in
      differentially increased Nox-1 elevation and ROS production leading to selective
      cell death of oncogenic H-Ras-expressing cells versus counterpart cells. We also
      found that FK228 treatment induced mitochondrial ROS and Mek1/2 activation,
      bypassing Raf-1, to downstream Erk1/2, participating in the induction of
      selective cell death. Thus, the pro-apoptotic abilities of Mek1/2 and Nox-1
      should be considered as potential targets in designing therapeutic protocols
      using FK228 to assure ROS-mediated cell death for treating cancer cells acquiring
      Ras activation.

PMID- 20700044
TI  - Anti-EMMPRIN antibody treatment of head and neck squamous cell carcinoma in an ex
      vivo model.
AB  - Targeting the molecular pathways associated with carcinogenesis remains the
      greatest opportunity to reduce treatment-related morbidity and mortality.
      Extracellular matrix metalloproteinase inducer (EMMPRIN), also known as CD147, is
      a cell surface molecule known to promote tumor growth and angiogenesis in
      preclinical studies of head and neck carcinoma making it an excellent therapeutic
      target. To evaluate the feasibility of anti-EMMPRIN therapy, an ex-vivo human
      head and neck cancer model was established using specimens obtained at the time
      of surgery (n=22). Tumor slices were exposed to varying concentrations of anti
      EMMPRIN monoclonal antibody and cetuximab for comparison purposes. Cetuximab is
      the only monoclonal antibody currently approved for the treatment of head and
      neck carcinoma. After treatment, tumor slices were assessed by
      immunohistochemistry and western blot analysis for apoptosis (TUNEL) and EMMPRIN
      expression. Of the tumor specimens 33% showed a significant reduction in mean ATP
      levels after treatment with cetuximab compared with untreated controls, whereas
      58% of the patients responded to anti-EMMPRIN therapy (P<0.05). Samples, which
      showed reactivity to anti-EMMPRIN, also had greater EMMPRIN expression based on
      immunohistochemistry staining (49%) when compared with nonresponders (25%,
      P=0.06). In addition, TUNEL analysis showed a larger number of cells undergoing
      apoptosis in antibody-treated tumor slices (77%) compared with controls (30%,
      P<0.001) with activation of apoptotic proteins, caspase 3 and caspase 8. This
      study shows the potential of anti-EMMPRIN to inhibit proliferation and promote
      apoptosis and suggests its future role in the targeted treatment of head and neck
      carcinoma.

PMID- 20700045
TI  - Comparative neuroscience of stimulant-induced memory dysfunction: role for
      neurogenesis in the adult hippocampus.
AB  - The discovery that the addictive drugs impair neurogenesis in the adult
      hippocampus has prompted the elaboration of new biological hypotheses to explain
      addiction and drug-induced cognitive dysfunction. Considerable evidence now
      implicates the process of adult neurogenesis in at least some critical components
      of hippocampal-dependent memory function. In experimental models, psychomotor
      stimulant drugs produce alterations in the rate of birth, survival, maturation
      and functional integration of adult-born hippocampal neurons. Thus some of the
      deleterious consequences of drug abuse on memory could result from the neurotoxic
      actions of drugs on adult hippocampal neurogenesis. In this review, we will first
      summarize preclinical and clinical literature on the disruptive effects of drugs
      such as cocaine and ecstasy in the areas of learning, memory and attention. We
      will also summarize data that document the widespread effects of stimulant drugs
      on progenitor activity and precursor incorporation in the adult dentate gyrus.
      Finally, we will examine evidence that supports the involvement of hippocampal
      neurogenesis in specific aspects of learning and memory function and we will
      consider critically the hypothesis that some of the negative consequences of drug
      abuse on cognition might be ascribed to deficits in adult hippocampal
      neurogenesis. Evidence suggests that stimulant abuse impacts negatively on at
      least four areas of memory/cognitive function that may be influenced by adult
      hippocampal neurogenesis: contextual memory, spatial memory, working memory and
      cognitive flexibility.

PMID- 20700047
TI  - Antidepressant effects of estrogens: a basic approximation.
AB  - The use of estrogenic compounds as antidepressants or as coadjuvants to
      facilitate the effect of antidepressants has reported controversial results,
      suggesting that many factors could influence their actions. This review analyzes,
      from a basic research perspective, the possible factors that may underlie the
      antidepressant action of estrogens alone or in combination. The possible
      mechanisms of action of estrogens alone and in combination with the selective
      serotonin reuptake inhibitor, fluoxetine, the selective noradrenaline reuptake
      inhibitor, desipramine, and the mixed serotonin/noradrenaline reuptake inhibitor,
      venlafaxine are reviewed, focusing on monoaminergic systems and estrogen
      receptors as main targets. The antidepressant effect of estrogens depends on the
      type of estrogen, treatment duration, doses, sex, time after ovariectomy, and
      age. Estrogens potentiate the antidepressant-like action of fluoxetine,
      venlafaxine, and desipramine and drastically shorten their latency of action. The
      antidepressant-like effect of estrogens alone or in combination with
      antidepressants seems to be mediated by monoaminergic and classic estrogen
      receptors, as WAY100635, an antagonist to the serotonin 1A receptor, idaxozan, an
      antagonist to alpha2 adrenergic receptors, and RU 58668, an estrogen receptor
      antagonist, blocked their antidepressant-like effect. In conclusion, estrogens
      produce antidepressant-like actions by themselves and importantly facilitate the
      action of clinically used antidepressants.

PMID- 20700048
TI  - Intracellular pathways underlying the effects of lithium.
AB  - This is a short overview focusing on the biochemical interactions underlying the
      protective effects of lithium at the neuronal level. These include lithium
      modulation of autophagy, growth factors, excitotoxicity, and a variety of
      mechanisms underlying cell death, neurogenesis, and neuronal differentiation. All
      these effects represent the result of a multifaceted pharmacology, which is
      becoming more and more complex. Nonetheless, when trying to dissect the various
      mechanisms of action of lithium, two primary targets emerge: glycogen synthase
      kinase 3beta and phosphatidylinositol phosphatase. The numerous lithium effects
      on biochemical systems are placed downstream of these two main mechanisms. At
      several steps, these mechanisms interconnect to each other, thus making it
      difficult to keep distinct the biochemical cascades promoted by lithium. In this
      way, it is not surprising that, despite being described as different phenomena at
      the behavioral level, molecular mechanisms underlying the effects of lithium on
      mood, motor activity, and sensitization overlap with those responsible for
      neuroprotection and neurorestoration. It is likely that the ancestral role of
      this ion as a modulator of cell survival, cell growth, movement, and mood is the
      consequence of a few molecular mechanisms operating in different neuronal
      networks, where a variety of cascade events take place. This review is an attempt
      to elucidate the primary effects of lithium to interconnect the simpler targets
      to the most complex pharmacological effects.

PMID- 20700046
TI  - Activators of G-protein signaling 3: a drug addiction molecular gateway.
AB  - Drug addiction is marked by continued drug-seeking behavior despite deleterious
      consequences and a heightened propensity to relapse not withstanding long, drug
      free periods. The enduring nature of addiction has been hypothesized to arise
      from perturbations in intracellular signaling, gene expression, and brain
      circuitry induced by substance abuse. Ameliorating some of these aberrations
      should abate behavioral and neurochemical markers associated with an 'addiction
      phenotype'. This review summarizes data showing that protein expression and
      signaling through the nonreceptor activator of G-protein signaling 3 (AGS3) are
      altered by commonly abused substances in rat and in in-vitro addiction models.
      AGS3 structure and function are unrelated to the more broadly studied regulator
      of G-protein signaling family. Thus, the unique role of AGS3 is the focus of this
      review. Intriguingly, AGS3 protein changes persist into drug abstinence.
      Accordingly, studies probing the role of AGS3 in the neurochemistry of drug
      seeking behavior and relapse are studied in detail. To illuminate this study,
      AGS3 structure, cellular localization, and function are covered so that an
      idealized AGS3-targeted pharmacotherapy can be proposed.

PMID- 20700049
TI  - (-)-Epigallocatethin-3-O-gallate counteracts caffeine-induced hyperactivity:
      evidence of dopaminergic blockade.
AB  - This experiment was designed to know whether (-)-epigallocatethin-3-O-gallate
      (EGCG) counteracts caffeine-induced hyperactivity, and its potential mechanisms
      in mice. EGCG inhibited methamphetamine-induced, cocaine-induced and caffeine
      induced horizontal hyperlocomotion and rearing activity. EGCG also inhibited
      hyperlocomotion and rearing activity induced by apomorphine, a D1/D2-like
      agonist. Moreover, EGCG inhibited climbing behavior, a typical stereotyped
      behavior induced by stimulation of dopamine receptors through the activation of
      those receptors by apomorphine. From this experiment, we suggest that EGCG
      inhibits hyperactivity induced by psychostimulants including caffeine, in part by
      modulating dopaminergic transmission, and these inhibitory effects of EGCG
      counteract the stimulant actions of caffeine in green tea.

PMID- 20700050
TI  - A safe Nd:YAG retroprosthetic membrane removal technique for keratoprosthesis.
AB  - PURPOSE: To describe a technique for Nd:YAG laser photodiscission of
      retroprosthetic membrane (RPM) in keratoprosthesis patients that minimizes damage
      to the optic. METHODS: Prospective review of Boston type I keratoprosthesis
      patients at 1 site who received Nd:YAG treatment for RPM from 2005 to 2009.
      Outcomes were based on slit-lamp examination of the optic immediately after YAG
      treatment, tactile intraocular pressure at follow-up, and complications from the
      outpatient procedure. RESULTS: The incidence of RPM was 24.1% (39 of 162 eyes).
      Of 26 RPM eyes receiving YAG treatment, 18 had 1 YAG treatment, 6 had multiple
      YAG treatments, and 2 had surgical excision despite multiple YAG treatments
      because of membrane thickness. All 26 eyes had no intraoperative complications,
      no damage to the optic from slit-lamp examination, and soft tactile intraocular
      pressures. CONCLUSION: Based on the office procedures from our patient base, YAG
      retroprosthetic membranectomy using a peripheral "can-opener" approach is
      effective and safe with no evident damage to the optic.

PMID- 20700051
TI  - Significant relationship between changes in brachial-ankle pulse wave velocity
      relative to blood pressure elevation and coronary artery disease.
AB  - OBJECTIVES: Based on well-established physiological theories, we studied
      correlations between changes in brachial-ankle pulse wave velocity (baPWV)
      relative to blood pressure (BP) elevation (elasticity of large-to-medium-sized
      arteries), and coronary artery disease (CAD). METHODS: The baPWV (in
      centimeters/second) and BP (in millimeters of mercury) were determined in 101
      patients before, during, and/or after a cold pressor test using a volume
      plethysmographic system. RESULTS: Significantly higher rates of increase in PWV
      relative to changes in BP were observed in the CAD(+) group than in the CAD(-)
      group when mean BP [median (25th-75th percentiles): 14.8 (8.3-24.9) vs. 8.6 (5.7
      11.4) cm/s/mmHg, P<0.0001], and systolic [10.1 (6.0-17.5) vs. 6.4 (4.4-10.6)
      cm/s/mmHg, P=0.0023] and diastolic BP [21.0 (14.0-34.4) vs. 10.8 (6.8-16.1)
      cm/s/mmHg, P<0.0001] were used as BP indices. Similarly, the rates of increase in
      baPWV showed a significant correlation with the extent of CAD. The rate of
      increase in baPWV obtained using the mean, systolic and diastolic BP as indices
      showed an area under the receiver operating characteristic curve of 0.68-0.76,
      sensitivity of 65-75%, and specificity of 65-75% for the detection of CAD. The
      area under the receiver operating characteristic curve, sensitivity, and
      specificity for the rate of increase were slightly higher than those for baseline
      baPWV and baseline baPWV/baseline BP ratio, but not to a significant degree.
      CONCLUSION: The rate of increase in baPWV relative to BP elevation determined by
      cold pressor test is significantly and moderately correlated with CAD. To
      identify patients with CAD, the rate of increase in baPWV relative to changes in
      BP can provide considerable, but limited, information.

PMID- 20700052
TI  - Coronary artery calcium and plaque association with left ventricular mass,
      assessed by multi-row detector computed tomography.
AB  - INTRODUCTION: Few studies have been published describing the association of
      coronary plaques and coronary artery calcium (CAC) to left ventricular (LV) mass
      and LV function using multi-detector computed tomography (MDCT). Coronary plaques
      can potentially influence the LV function. We sought to evaluate LV mass and
      function on MDCT and its correlation with CAC and plaque burden in the coronary
      arteries. METHODS: We included 197 symptomatic patients from the multicenter
      ACCURACY Study. The LV mass was measured manually using Advantage 4.4
      workstation. Interobserver variability of LV mass was assessed using 34 randomly
      selected studies. LV mass was indexed to the body surface area. The coronary
      plaque severity was assessed in each segment using MDCT, following the 15 segment
      American Heart Association model. Plaque and segment scores were calculated
      accordingly. Statistical analysis using multiple logistic regression analysis was
      performed. RESULTS: We divided the cohort into those with CAC=0 [n=67 (34%)] and
      those with CAC greater than 0 [n=130 (66%)]. A significant correlation was found
      between indexed LV mass and CAC, plaque, and segment scores in both adjusted and
      unadjusted models. A significant association was observed between nonindexed LV
      mass with CAC, MDCT plaque score and segment score upon adjusting for various
      cardiovascular risk factors. A significant correlation was found between
      hyperlipidemia, hypertension, family history of CAD, and greater than 50% and
      greater than 70% stenosis on invasive cardiac catheterization with LV mass (all
      P<0.05). CONCLUSION: To our knowledge, this is the first study evaluating
      coronary plaque on computed tomographic angiography with LV mass. We were able to
      show a significant correlation of LV mass with CAC score, and with total plaque
      and total segment scores. The poor prognosis associated with increased CAC scores
      may be partially explained by this association with increased LV mass.

PMID- 20700053
TI  - Early detection of acute posterior myocardial infarction using body surface
      mapping and SPECT scanning.
AB  - BACKGROUND: Many patients with non-ST elevation myocardial infarction (NSTEMI)
      may have posterior STEMI, which should be emergently treated with reperfusion
      strategies but is difficult to identify by 12-lead ECG. OBJECTIVES: To compare
      the initial ECG and body surface map (BSM) for the diagnosis of posterior MI as
      verified by single-photon emission computed tomography (SPECT) and cTroponin T.
      METHODS: Patients with chest pain greater than 20 min at rest with either ST
      depression of at least 0.1 mV in at least one of leads I, aVL or V1-V6 on ECG or
      STE at least 0.05 mV in at least one posterior lead on the BSM which underwent
      early SPECT scan. RESULTS: Sixty patients (87%, 60 out of 69 with interpretable
      SPECT) had a posterior wall perfusion defect, all had cTroponinT (>0.09 ng/ml)
      and thus had posterior MI. Initial ECG showed STE in 24 (40%, 24 out of 60): 36
      were non-diagnostic (60%, 36 out of 60). STE on BSM identified inferior MI in
      seven patients (12%, 7 out of 60), posterior in 32 patients (53%, 32 out of 60),
      and nine patients had right ventricular (15%, 9 out of 60). Twelve had no STE
      (20%, 12 out of 60). Of the patients with posterior MI and non-diagnostic ECGs,
      53% (19 out of 36) were posterior MI by the BSM and six (17%, 6 out of 36) right
      ventricular MI only. The BSM correctly identified 53% (32 out of 60) (95%
      confidence interval 40-66%) of posterior MI. Of the 60 patients with posterior
      MI, 60% (36) had non-diagnostic ECGs: the BSM identified 42% (25) either as
      posterior MI or right ventricular MI only. CONCLUSION: We have shown that the BSM
      diagnoses significantly more posterior MI than the 12-lead ECG, allowing early
      identification of these patients so that maximum benefit from early reperfusion
      strategies can be gained.

PMID- 20700054
TI  - All-cause mortality of patients with dyslipidemia up to 19 years after a
      multidisciplinary lifestyle modification programme: a randomized trial.
AB  - BACKGROUND: Many studies have shown that individual lifestyle factors are
      associated with cardiovascular mortality and all-cause mortality. Observational
      studies of comprehensive programmes have reported risk reductions. The objectives
      were to assess the long-term all-cause mortality by diagnosis in patients
      referred to a lifestyle modification programme, aimed at combating coronary heart
      disease and stroke. METHODS: A randomized trial with 325 patients referred to the
      centre between 1988 and 1989 for dyslipidemia, hypertension, type 2 diabetes and
      coronary heart disease; 239 patients were randomized to the programme, 86
      randomized to usual care. Cases were admitted to the centre in groups of 30 for a
      4-week residential comprehensive activity, in total 114 full-time hours, focusing
      on food preferences and selections, and physical exercise. The activities were
      repeated during a 4-day revisit to the centre 1 year and 5 years after the 4-week
      intervention. Controls were referred back to their doctors, mainly in primary
      care, for usual care. Main outcome measure was all-cause mortality during 11-12
      and 18-19 years after intervention. RESULTS: At follow-up 11-12 years after
      referral, the relative risk reduction (RRR) was 76% with the intention-to-treat
      analysis among cases admitted for dyslipidemia (hazards ratio 0.24, confidence
      interval 0.06-0.89, P = 0.033). After 18-19 years, the RRR was 66% (hazards ratio
      0.34, confidence interval 0.13-0.88, P = 0.026). No RRR was found for the other
      three diagnoses. CONCLUSION: Patients admitted for dyslipidemia reached a real
      long-term RRR of all-cause mortality. They had by definition a need for this
      programme.

PMID- 20700055
TI  - Prevalence, treatment and control of dyslipidaemia in Switzerland: still a long
      way to go.
AB  - BACKGROUND: There is little information regarding the prevalence and management
      of dyslipidaemia in Switzerland. DESIGN: Cross-sectional population-based study
      of 3238 women and 2846 men aged 35-75. METHODS: Dyslipidaemia prevalence,
      treatment and control were defined according to PROCAM guidelines adapted to
      Switzerland. RESULTS: About 29% of the overall sample presented with
      dyslipidaemia, of which 39% were treated and 58% of those treated were
      controlled. Among the 710 patients with personal history of cardiovascular
      disease (CVD) and/or diabetes, 632 (89%) presented with dyslipidaemia, of which
      278 (44%) and 134 (21%) patients were treated and adequately controlled,
      respectively. On multivariate analysis, hypolipidaemic drug treatment was
      positively related with age and body mass index (P for trend <0.001), and
      negatively related with smoking status (P for trend <0.002), whereas personal
      history of CVD and/or diabetes had no effect [odds ratio (OR)=1.12, 95%
      confidence interval (CI): 0.90-1.38]. Adequate control of lipid levels was
      negatively related with female sex (OR=0.65, 95% CI: 0.45-0.94) and personal
      history of CVD and/or diabetes (OR=0.42, 95% CI: 0.30-0.59). When personal
      history of CVD and/or diabetes was replaced by PROCAM risk categories, patients
      in the highest risk were also less well controlled. CONCLUSION: In this
      population-based study, one-third of the participants was dyslipidaemic, but less
      than half was treated and only one-fifth was adequately controlled. The low
      treatment and control levels among individuals at high risk for CVD calls for a
      better application of recommendations regarding personal preventive measures.

PMID- 20700056
TI  - Assessment of mammographic density before and after first full-term pregnancy.
AB  - Mammographic density (MD) has consistently been found as one of the strongest
      breast cancer risk factors. In our study, both qualitative and quantitative
      density measurements were performed in a hospital-based group of premenopausal
      women before and after first full-term pregnancy providing an opportunity for
      direct evaluation of the effects of one pregnancy on MD. Mammograms were obtained
      from 23 women before and after first full-term pregnancy and from 28 nulliparous
      controls. MD was determined by a standard qualitative assessment method using the
      Breast Imaging Reporting and Data System, and a quantitative computer-based
      threshold method (0-100%). The mean age at mammography before and after pregnancy
      was 31 and 34 years, respectively, with a mean difference of 40 months between
      mammographies. The quantitative density assessment showed a significant reduction
      in relative MD after pregnancy of 12 percentage points (8.6-15.4), compared with
      3.1 (0.0-6.2) in the nulliparous control group (P<0.001). A reduction in MD of
      more than 10% was seen in 52% of the patients, compared with 18% of the controls.
      The qualitative density assessment confirmed a reduction in MD after pregnancy by
      one Breast Imaging Reporting and Data System category (P=0.02). This longitudinal
      study showed that MD can be influenced by one full-term pregnancy. This effect
      was seen with both quantitative and qualitative assessment methods. It may be
      hypothesized that breast cancer risk reduction associated with pregnancy is
      mediated through a direct reduction of MD, and MD assessment might be
      incorporated in individualizing risk assessment and prevention.

PMID- 20700057
TI  - Efficacies of papaverine and sildenafil in the treatment of erectile dysfunction
      in early-stage paraplegic men.
AB  - The aim of the study was to determine which vasoactive agent was more efficacious
      for erectile dysfunction (ED), intracavernosal papaverine or oral sildenafil, in
      paraplegic men within the first year after injury by using a penile color Doppler
      ultrasound as a quantitative imaging method and to determine the association
      between responses to these two vasoactive agents and factors such as neurological
      lesion level and lesion severity. A total of 31 male in-patients with spinal cord
      injury, aged over 18 years, and with neurological lesions below the T6 level
      within the first year after injury with ED were included. Visual and auditory
      sexual stimulus (VASS) on day 1 (group 1), VASS with 25 mg intracavernosal
      papaverine (group 2) and after a wash-out period of papaverine on day 2, and VASS
      with 50 mg oral sildenafil on day 5 (group 3) were administered to each patient.
      Measurements of the peak systolic velocity and end diastolic velocity, which were
      used as vascular parameters during each procedure type, were taken using penile
      color Doppler ultrasound. Considering the severity of the lesion and the levels
      of the neurological lesion, there was a statistically significant difference
      between the PSV values of the group 1 and the other two groups (P<0.05). There
      was no statistically significant difference between the peak systolic velocity
      and end diastolic velocity values of groups 2 and 3 (P>0.05) in terms of both the
      severity and the levels of the lesion. Efficacies of intracavernosal papaverine
      hydrochloride or oral sildenafil citrate for ED were similar at all neurological
      lesion levels and lesion severity in paraplegic men within the first year after
      spinal cord injury.

PMID- 20700058
TI  - Dried blood spot HIV-1 RNA quantification using open real-time systems in South
      Africa and Burkina Faso.
AB  - There is an urgent need to assess the accuracy/feasibility of using dried blood
      spots (DBS) for monitoring of HIV-1 viral load in resource-limited settings. A
      total of 892 DBS from HIV-1-positive pregnant women and their neonates enrolled
      in the Kesho Bora prevention of mother-to-child transmission trial conducted in
      Durban (South Africa) and Bobo-Dioulasso (Burkina Faso) between May 2005 and July
      2008 were tested for HIV-1 RNA. The combination Nuclisens extraction method
      (BioMerieux)/Generic HIV Viral Load assay (Biocentric) was performed using one
      DBS (in Durban) versus 2 DBS (in Bobo-Dioulasso) on 2 distinct open real-time
      polymerase chain reaction instruments. DBS HIV-1 RNA results were compared with
      plasma HIV-1 RNA and HIV serology results used as the gold standards. The limits
      of detection of assays on DBS were 3100 and 1550 copies per milliliter in Durban
      and Bobo-Dioulasso, respectively. DBS HIV-1 RNA values correlated significantly
      with plasma levels (n = 327; R = 0.7351) and were uniformly distributed according
      to duration of DBS storage at -20 degrees C (median duration, 280 days). For
      early infant diagnosis, the sensitivity and specificity were 100% (95% confidence
      interval: 97.2 to 100.0 and 96.5 to 100.0, respectively). HIV-1 viral load
      kinetics in DNase-pretreated DBS were similar to those obtained in plasma
      specimens among 13 patients receiving antiretroviral treatment. HIV-1 RNA
      findings from serial infant DBS collected prospectively (n = 164) showed 100%
      concordance with HIV serology at 18 months of life. Our findings strongly
      advocate the implementation of DBS HIV-1 RNA testing in remote areas from low
      income and middle-income countries.

PMID- 20700059
TI  - A role for syndecan-1 and claudin-2 in microbial translocation during HIV-1
      infection.
AB  - Microbial translocation from the gastrointestinal tract has been implicated in
      chronic activation of the immune system during progressive HIV-1 infection by ill
      defined mechanisms. We recently identified a gene encoding syndecan-1 (SYN1) in
      microarray studies of HIV-1 infection in lymphatic tissues and show here that
      increased expression of SYN1 in the gut of HIV-1-infected individuals is
      associated with increased microbial translocation. We further show that: (1)
      microbial access to SYN1 in the intestinal epithelium could be mediated by
      compromised barrier function through the upregulation of claudin-2; (2) increases
      in SYN1 and microbial translocation are associated with systemic immune
      activation; and (3) SYN1 expression and microbial translocation are inversely
      correlated with peripheral blood CD4 T-cell counts. We thus propose a new
      mechanism in which claudin-2 and SYN1 work in concert to enhance microbial
      translocation across the intestinal epithelial barrier to contribute to chronic
      immune activation and CD4 T-cell depletion.

PMID- 20700061
TI  - Detection of annexin A autoantibodies in sera from colorectal cancer patients.
AB  - BACKGROUND: Annexins (ANXAs) belong to a superfamily of closely related calcium
      and membrane-binding proteins and are overexpressed in some carcinomas. The
      overexpression of ANXAs presumably induces an autoantibody response, but this has
      not been demonstrated for sera from colorectal cancer (CRC) patients. STUDY: We
      examined serum samples from 220 CRC patients and 216 healthy volunteers to
      evaluate the ANXA autoantibody response in patients by using an enzyme-linked
      immunosorbent assay with recombinant ANXA A4 as the antigen. RESULTS: The
      sensitivity of the anti-ANXA response from CRC patient sera was about 85% and the
      specificity was about 61.6%. When a cut-off value of 5.0 ng/mL was chosen for
      carcinoembryonic antigen (CEA) in the same sera samples, the sensitivity and
      specificity values were 43.2% and 85.2%, respectively. Combined detection using
      ANXA autoantibodies and CEA produced better sensitivity (71.8%) and specificity
      (79.2%) compared with CEA sensitivity (43.2%) and anti-ANXA specificity (61.6%).
      The area under a receiver operating characteristic curve was 0.794 for ANXA
      autoantibodies, 0.666 for CEA, and 0.84 for both markers together. Importantly,
      in comparison to CEA (27.5% seropositivity), ANXA autoantibody showed a
      remarkable change (81.3% seropositivity) at the early stage of CRC. CONCLUSIONS:
      Measurement of ANXA autoantibody levels may provide an alternative detection
      indicator for CRC, particularly among early-stage patients.

PMID- 20700063
TI  - Keratinocytes drive melanoma invasion in a reconstructed skin model.
AB  - Melanoma progression is a multistep progression from a common melanocytic nevus
      through the radial growth phase, the invasive vertical growth phase finally
      leading to metastatic spread into distant organs. Migration and invasion of tumor
      cells requires secretion of proteases to facilitate remodeling of the
      extracellular matrix including basement membranes. Here we used a reconstructed
      skin model to investigate melanoma growth and invasion in vitro. Using this model
      we show that the dermoepidermal basement membrane prevents the invasion of
      metastatic melanoma BLM and MV3 cells in the absence of a stratified epidermis.
      In the reconstructed skin model, matrix metalloproteinase-9, a protease activated
      early in melanoma development, is secreted by the keratinocytes and subsequently
      activated by an unknown soluble factor secreted by the melanoma cells. The
      dynamic interplay between keratinocytes and melanoma cells is further shown by an
      altered growth pattern of melanoma cells and the finding that a reconstructed
      epidermis induces invasion. Overall, our findings show that the invasive behavior
      of melanoma cells is determined by the melanoma cells themselves, but that the
      interplay between surrounding keratinocytes and the melanoma cells plays an
      important role in melanoma invasion.

PMID- 20700064
TI  - Sexual problems in breast cancer survivors: do not turn good news into no news.

PMID- 20700060
TI  - Serious fatal and nonfatal non-AIDS-defining illnesses in Europe.
AB  - BACKGROUND: Little is known about the incidence and risk factors for serious non
      AIDS-defining events. METHODS: The incidence of non-AIDS events (malignancies,
      end-stage renal disease, liver failure, pancreatitis, cardiovascular disease),
      and AIDS after January 1, 2001, was calculated; Poisson regression was used to
      investigate factors associated with non-AIDS and AIDS. RESULTS: Among 12,844
      patients, 1058 were diagnosed with a non-AIDS event [incidence 1.77 per 100
      person-years of follow-up; 95% confidence interval (CI): 1.66 to 1.87]; 462
      patients (43.7%) died. The incidence of AIDS (1025 diagnoses; 339 deaths, 33.1%)
      was 1.72 per 100 person-years of follow-up (1.61 to 1.83). After adjustment,
      older age [incidence rate ratio (IRR): 1.71 per 10 years older, 95% CI: 1.60 to
      1.83], diabetes (IRR: 1.49, 95% CI: 1.22 to 1.82) and hypertension (IRR: 1.63,
      95% CI: 1.43 to 1.87) were associated with non-AIDS events. Compared with
      patients without an event, there was a 4-fold increased risk of death after an
      AIDS event (relative hazard: 4.14; 95% CI 3.47 to 4.94) and almost a 7-fold
      increased risk of death after a non-AIDS event (relative hazard: 6.72; 95% CI:
      5.61 to 8.05). CONCLUSIONS: Non-AIDS events were common in the combination
      antiretroviral therapy era and associated with considerably mortality. Evidence
      on the impact of modifying immunodeficiency and lifestyle-related factors on the
      risk of non-AIDS events in HIV-infected persons is an important but unmet
      research need.

PMID- 20700065
TI  - Study on retinal dopamine transporter in form deprivation myopia using the
      radiopharmaceutical tracer 99mTc-TRODAT-1.
AB  - PURPOSE: To investigate the distributions and changes in dopamine transporters
      (DATs) using Tc-TRODAT-1 ([Tc-(2((2-(((3-(4-chlorophenyl)-8-methyl-8
      azabicyclo(3,2,1)-oct-2-yl)-methyl)(2-mercaptoethyl)amino)ethyl)amino)ethane
      thiolato(3-)-N2,N2',S2,S2)oxo-(1R-(exo-exo)))]) in form deprivation myopia
      retina. METHODS: Pigmented guinea pigs aged 3 weeks were randomly assigned into
      two groups: form-deprivation myopia and normal control group. The test group wore
      a translucent goggle covering randomly for 4 weeks, and both groups underwent
      biometric measurement before and after the experiment. Both Micro-single-photon
      emission computed tomography (SPECT) imaging and ex-vivo autoradiography were
      performed with the injection of Tc-TRODAT-1 on the 4th week for all the guinea
      pigs. RESULTS: The retinas were clearly resolved with Tc-TRODAT-1 in both Micro
      SPECT imaging and ex-vivo autoradiography. In Micro-SPECT imaging, the ratio of
      Tc-TRODAT-1 uptake in the myopic retinas (11.55+/-2.80) was 3.64+/-1.40 lower
      than that in the normal control eyes (15.20+/-1.98, P=0.026, F=2.94, t=2.605),
      and 2.35+/-1.05 lower than that in the fellow eyes (13.90+/-2.04, P=0.003,
      t=5.476). In ex-vivo autoradiography, the ratio of Tc-TRODAT-1 uptake in the
      myopic retina (95.52+/-12.04) was 18.54+/-5.86 lower than in the normal control
      eyes (114.06+/-7.81, P=0.01, F=0.331, t=3.164), and was 16.95+/-5.78 lower than
      in the fellow eyes (112.47+/-15.67, P=0.001, t=7.179). CONCLUSION: Tc-TRODAT-1
      can be used to trace the distributions and changes in DAT in the retina. DATs in
      the myopic retinas were lower than that in the fellow and normal control eyes.
      Radionuclide tracing may provide a new approach in vivo for further studies on
      the dopamine system in myopia.

PMID- 20700066
TI  - Posterior bladder layering of excreted 18F-FDG on PET/CT.
AB  - PURPOSE: This study was carried out to determine the frequency, characteristics
      and possible causes and clinical significance of occasionally observed posterior
      layering of excreted 2-deoxy-2-[F]fluoro-D-glucose (F-FDG) in the bladder.
      PROCEDURES: A review of 567 consecutive patients referred for positron emission
      tomography/computerized tomography studies was performed. Urinary bladder size
      was measured in patients with and without layering. Urine samples from two
      patients with layering were imaged ex vivo. RESULTS: Twenty-four of 567 studies
      (4%) showed F-FDG posterior bladder layering. Mean volume+/-SD of the bladder was
      175+/-161 ml in patients with layering and 93+/-83 ml in patients without
      layering. Urine samples collected from two randomly chosen patients with layering
      in vivo failed to show layering ex vivo. CONCLUSION: Posterior F-FDG layering
      occurs in 4% of positron emission tomography/computerized tomography cases and
      highly correlates with bladder volume. The mechanism is hypothesized to be
      because of slow F-FDG excretion in patients with a distended urinary bladder
      resulting in delayed mixing with urine, but needs to be further investigated with
      a more comprehensive study.

PMID- 20700067
TI  - Reduction in coronary and peripheral vasomotor function in patients with HIV
      after initiation of antiretroviral therapy: a longitudinal study with positron
      emission tomography and flow-mediated dilation.
AB  - OBJECTIVES: The mechanisms underlying the increased cardiovascular risk in
      patients with HIV on antiretroviral therapy (ART) are not known. Our aim was to
      study the endothelial function of the coronary arteries by cardiac perfusion
      positron emission tomography (PET) in patients with HIV initiating ART. In
      addition, flow-mediated dilation (FMD) of the brachial artery was measured.
      METHODS: Patients with HIV scheduled to initiate ART (n=12) were included. NH3
      perfusion PET and FMD scans were performed both before and 5 weeks (24-67 days)
      after initiation of ART. Data were compared with paired t-tests and a P value of
      less than 0.05 was considered significant. RESULTS: No changes were found in the
      pulse-pressure-corrected myocardial rest perfusion (1.22+/-0.07-1.09+/-0.05
      ml/min/g tissue, NS) or cold pressor reserve (1.18+/-0.08-1.27+/-0.05, NS).
      However, the maximal myocardial perfusion decreased 31% from 2.50+/-0.25 to
      1.73+/-0.15 ml/min/g tissue (P=0.009) and the myocardial perfusion reserve
      decreased 20% from 3.11+/-0.32 to 2.48+/-0.25 (P=0.042). FMD decreased from
      8.68+/-1.70 to 4.58+/-0.93% (P=0.027). No change was observed in nitroglycerin
      mediated dilation (12.8+/-1.0-14.4+/-1.4%, NS). CONCLUSION: In patients with HIV
      initiating ART, signs of development of endothelial dysfunction assessed by
      coronary perfusion PET and FMD were found early after starting medication.

PMID- 20700068
TI  - Oncocytic carcinoma of the lacrimal gland in a patient with neurofibromatosis.
AB  - Oncocytic carcinoma (OCA) is rare, and although its occurrence in the lacrimal
      gland has been documented, clinical and histologic data are lacking. The authors
      report the first case of OCA of the lacrimal gland histologically proven in a
      patient with neurofibromatosis (NF). An 81-year-old man affected by type 1 NF
      presented with a 2-year history of left proptosis and visual loss. Orbital CT
      scan showed a mass in the lacrimal gland fossa infiltrating the globe, lateral
      rectus muscle, and bone. An incisional biopsy revealed a primary high-grade
      malignancy, and the patient underwent orbital exenteration followed by
      postoperative adjunctive radiotherapy. Six months after the operation, the
      patient was alive, without evidence of recurrent or metastatic disease. OCA is a
      high-grade neoplasm with infiltrative growth pattern and tendency to recur and
      metastasize. Its occurrence in association with NF has not been documented
      before, but clinicians should be aware of this possibility when evaluating
      proptosis in NF patients. Radical surgical excision, followed by adjunctive
      radiotherapy, is considered the treatment of choice, but the prognosis remains
      guarded.

PMID- 20700069
TI  - Late-onset orbital hematoma secondary to alloplastic orbital implant mimicking
      transient ischemic attacks.
AB  - Alloplastic orbital implants are commonly used by surgeons in the repair of
      orbital wall defects. They are generally well tolerated, but they may cause late
      onset complications. The authors present the case of a 65-year-old man with a
      history of left orbital floor fracture repair 25 years prior using a silicone
      orbital implant. He presented with a 1-year history of recurrent binocular
      vertical diplopia previously diagnosed as transient ischemic attacks. The patient
      subsequently presented with symptoms suggestive of orbital cellulitis, and after
      failure to respond to antibiotic therapy, he underwent surgical removal of the
      implant, revealing a large orbital hematoma. This case represents an unusual
      presentation of a known complication associated with orbital implant placement in
      a patient with previously diagnosed cerebrovascular disease as the cause of his
      neuroophthalmologic symptoms.

PMID- 20700070
TI  - Fibrolipoma of the orbit.
AB  - A 47-year-old woman presented with a growing mass on the lateral rim of orbit.
      Orbital CT revealed a well-circumscribed soft tissue mass in the right lateral
      orbit, with focal hyperostosis of the adjacent zygomatic bone. MRI showed a
      lesion of mixed T1-signal intensity, which became hypointense after fat
      suppression. The lesion was excised, and the diagnosis of orbital fibrolipoma was
      made by histopathologic examination. There was no evidence of tumor after 12
      months of follow-up. Orbital fibrolipoma is a rare variant of lipoma, with only 1
      case described previously. It should be considered in the differential diagnosis
      of orbital mass.

PMID- 20700071
TI  - The porous polyethylene/bioglass spherical orbital implant: a retrospective study
      of 170 cases.
AB  - PURPOSE: To report patient outcomes after placement of porous polyethylene
      (PPE)/bioglass (BG) orbital implants for primary enucleation or secondary
      implantation. DESIGN: Retrospective chart review in one surgeon's practice
      (J.D.N.). METHODS: A chart review of all patients who underwent placement of
      PPE/BG orbital implants was performed. Data included patient's age, gender,
      surgical indication, prior ocular surgery, medical history, procedure performed,
      implant size, and postoperative complications. RESULTS: PPE/BG implants were
      placed in 170 sockets. Seventy-seven patients were women, and 85 were men. One
      hundred forty patients underwent primary enucleation and placement of an implant,
      and 22 patients underwent secondary implantation. One hundred sixty-one patients
      did well after orbital implantation with a comfortable socket, quiet conjunctiva,
      and motility. Complications occurred in 9 patients (5.3%). Excessive discharge
      alone occurred in 2 patients (1.2%). Seven sockets undergoing primary enucleation
      and implant placement had implant exposure. One patient had an early exposure,
      and 6 had late exposures. All exposures were successfully treated with
      antibiotics or additional surgery. Secondary surgeries were required by some
      patients, but not due to implant complications, included ectropion repair in 5
      patients (2.9%) and volume augmentation in 3 patients (1.7%). CONCLUSIONS: The
      PPE/BG orbital implant may be a useful implant for orbital reconstruction after
      primary enucleation or as a secondary implant.

PMID- 20700072
TI  - Low outflow distensible venous malformations of the anterior orbit: presentation,
      hemodynamic factors, and management.
AB  - PURPOSE: To describe a subclass of venous malformations of the orbit whose
      hemodynamic properties make them ideal for treatment with the technique of
      intraoperative embolization using cyanoacrylate glue followed by direct surgical
      excision. METHODS: A retrospective, noncomparative clinical study of 3 patients
      with "low-outflow" venous lesions of the anterior orbit who underwent treatment
      with the above technique in January 2008 and were followed for 2 years. RESULTS:
      Three patients presented with venous malformations of the orbit and elected to
      undergo surgical intervention. All cases demonstrated clinical and/or
      radiographic evidence of slow distensibility and were characterized by limited
      outflow through one or a few draining veins. All underwent intraoperative
      embolization using cyanoacrylate glue followed by direct surgical excision. In
      all cases, the surgical dissection of the lesion postgluing was straightforward.
      The boundary between the lesion and surrounding normal tissues was well
      demarcated, meticulous hemostasis was easy to maintain, and complete surgical
      excision was achieved. All 3 patients are doing well after 2 years with no
      recurrence of their lesions. CONCLUSIONS: "Low-outflow" venous lesions of the
      orbit can be safely treated with intraoperative embolization using cyanoacrylate
      glue followed by direct surgical excision, thereby ensuring complete removal of
      the lesion and minimizing chances of recurrence.

PMID- 20700073
TI  - Visual acuity recovery in traumatic optic neuropathy following endoscopic optic
      nerve decompression: a case report.
AB  - A 59-year-old Chinese man presented with no light perception in the left eye 1
      day following functional endoscopic sinus surgery. The patient underwent
      endoscopic optic nerve decompression with topical and systemic application of
      nerve growth factor and steroids after a failed trial of high-dose intravenous
      corticosteroids. Visual acuity improved to 20/25 at 3 weeks and remained stable
      at 9 months. Reports of full visual recovery are exceedingly rare following this
      functional endoscopic sinus surgery complication.

PMID- 20700074
TI  - Modified eyelid crease approach frontalis suspension without brow incision.
AB  - A 10-year-old boy with Noonan syndrome presented with bilateral ptosis. He had a
      history of keloid scarring. A modified technique of frontalis suspension with
      autogenous fascia lata is described to avoid forehead wounds. This uses an eyelid
      crease incision, dissection under the orbicularis to the orbital rim, and passage
      of the fascia lata into a shallow arc through the frontalis muscle. It is then
      passed inferiorly through the septum and secured to the tarsus.

PMID- 20700075
TI  - Closure of mid-posterior Tenon's capsule in enucleation.
AB  - PURPOSE: To evaluate the potential advantages of closing mid-posterior Tenon's
      capsule during enucleation surgery by comparing its thickness and relative tissue
      strength with anterior Tenon's capsule. To evaluate surgical outcomes of
      enucleation using mid-posterior Tenon's capsule closure. METHODS: This is an
      experimental laboratory study and retrospective surgical case series. Histologic
      examination of Tenon's capsule was performed on permanently fixated human orbital
      specimens. Suture pull-out testing as a measure of tissue strength was performed
      on anterior and mid-posterior Tenon's capsule in nonfixated human cadaver orbits.
      A retrospective review of enucleations with primary orbital implant placement
      performed by the authors between 1998 and 2008 was conducted to determine the
      surgical outcomes of enucleation using closure of mid-posterior Tenon's capsule.
      RESULTS: Histologic analysis showed the average thickness of mid-posterior
      Tenon's capsule to be 121% greater than that of the anterior portion (518 vs. 234
      MU, p < 0.001). Suture pull-out strength was 84% higher in mid-posterior versus
      anterior Tenon's capsule (741 vs. 1298 g, p = 0.016). Of the 103 enucleations
      performed by the authors (54 with unwrapped silicone implants and 49 with
      unwrapped porous polyethylene), there were 2 cases (1.9%) of implant extrusion
      and 1 case (1%) of implant exposure. CONCLUSION: From a structural and
      biomechanical standpoint, mid-posterior Tenon's capsule is significantly thicker
      and stronger than anterior Tenon's capsule, theoretically providing a superior
      barrier to orbital implant exposure and extrusion after enucleation.

PMID- 20700076
TI  - CT and orbital ultrasound findings in a case of Castleman disease.
AB  - A 53-year-old man with a 2-month history of left periorbital swelling was found
      to have a large solid intraconal mass on CT scan. Orbital ultrasound showed that
      the lesion had a cavernous pattern of internal reflectivity. Histopathology
      revealed hyaline-vascular type Castleman disease (CD). This article represents
      the first reported orbital ultrasound findings in CD. The findings of CT scan and
      ultrasound may be useful in the preoperative evaluation of orbital hyaline
      vascular type CD.

PMID- 20700077
TI  - The importance of keeping the chin up in graves orbitopathy.
AB  - A 42-year-old white woman suffering from mild euthyroid Graves orbitopathy for 6
      years experienced recent-onset upper eyelid swelling, double vision, diminished
      vision, and reduced visual field of the right eye. Examination of the right eye
      showed decreased visual acuity, relative afferent pupillary defect, hypotropia
      with severely restricted elevation, upper visual field defect, impaired color
      contrast discrimination, and abnormal pattern visual evoked potential, but the
      Ishihara color plate reading and the optic disc appearance were normal. The left
      eye was normal, except for marked elevation restriction. On CT scan, the inferior
      rectus muscles were asymmetrically enlarged. These findings were suggestive of
      unilateral dysthyroid optic neuropathy, and a 2-week course of pulsed high-dose
      intravenous corticosteroids was subsequently administered. Since there was no
      improvement, the clinical examinations and tests were repeated, with the patient
      positioned in chin lift so that the right hypotropic eye was looking straight
      ahead. All tests normalized instantly and completely.

PMID- 20700078
TI  - Epidemiology and outcome of invasive fungal diseases in patients with chronic
      granulomatous disease: a multicenter study in France.
AB  - BACKGROUND: Chronic granulomatous disease (CGD) is a rare inherited phagocytic
      disorder resulting in an increased susceptibility to infections including
      invasive fungal diseases (IFDs) and inflammatory complications. This study is
      aimed at assessing the incidence, prevalence, and outcome of IFDs among CGD
      patients followed in France. METHODS: CGD patients were identified through the
      French national registry for primary immunodeficiencies (PID) held by the French
      national reference Centre of PID (Centre de Reference Deficits Immunitaires
      Hereditaires), which comprises a total of 3083 patients including 155 with CGD
      followed between 1976 and 2008. A questionnaire was filled out for each episode
      of IFD. Information retrieved included a description of the IFD using the 2008
      European Organization for Research and Treatment of Cancer/Mycoses Study Group
      IFD definition criteria. RESULTS: Of CGD patients, 42.6% (66/155) developed at
      least 1 episode of IFD. Overall incidence of IFD was 0.040/patient-years (1862
      patient-years of total follow-up). IFD incidence was found to be significant
      while receiving itraconazole prophylaxis compared with no prophylaxis (0.027 vs.
      0.053 IFD/patient-years; P < 0.01). Median age at IFD diagnosis was 6.5 years
      (3.3-11.3). The most common fungal genus was Aspergillus sp. accounting for 40%
      of all IFDs. Of the IFDs, 42.5% were proven, 30.0% probable, and 27.5% possible.
      Of all IFD episodes, 52.5% were treated by antifungal monotherapy, mostly by
      amphotericin B. Survival was reduced in IFD patients compared with those without
      it (log-rank 0.04). CONCLUSIONS: IFDs are a frequent and life-threatening
      complication in CGD patients. Itraconazole significantly reduces its incidence
      and should be recommended in absence of better alternatives.

PMID- 20700079
TI  - Chronic suppurative otitis media in a birth cohort of children in Greenland:
      population-based study of incidence and risk factors.
AB  - BACKGROUND: Inuits of the Arctic experience very high rates of chronic
      suppurative otitis media (CSOM), yet world-wide, very little is known about the
      epidemiology of CSOM. The study aims were to determine incidence, median age at
      debut, risk factors, and associated population attributable risks for CSOM in
      young children in Sisimiut, the second biggest town of Greenland (population
      5400), where living conditions are relatively western and approximately 90% are
      Inuits. METHODS: A population-based birth cohort of 465 children aged between 0
      and 4 years was followed for a 2-year period (1996 to 1998), and cases of CSOM
      were registered based on medical history and clinical examinations. Kaplan-Meier
      curves were used for estimations of cumulative risk and Cox regression analyses
      for hazard rates associated with risk factors. RESULTS: Cumulative risk of CSOM
      at 4 years of age was 14%, and median age at debut was 336 days. Risk factors
      were attending childcare centers (hazard ratio [HR]: 3.18, 95% confidence
      interval [CI]: 1.53- 6.61), having smokers in the household (HR: 4.56, 95% CI:
      1.07-19.4), having a mother who reported a history of purulent ear discharge
      (3.27, 95% CI: 1.74-6.13), having a high burden of upper respiratory tract
      infections (HR: 1.19, 95% CI: 1.03-1.37), and being Inuit (HR: 5.56, 95% CI: 0.78
      50). CONCLUSIONS: Greenlandic children have high rates of CSOM with debut early
      in life, but the identified risk factors and the associated population
      attributable risks indicate that preventive measures regarding use of childcare
      centers and passive smoking may reduce the high frequency of CSOM in this high
      risk population.

PMID- 20700080
TI  - In vivo electrical conductivity across critical nerve gaps using poly(3,4
      ethylenedioxythiophene)-coated neural interfaces.
AB  - BACKGROUND: Bionic limbs require sensitive, durable, and physiologically relevant
      bidirectional control interfaces. Modern central nervous system interfacing is
      high risk, low fidelity, and failure prone. Peripheral nervous system interfaces
      will mitigate this risk and increase fidelity by greatly simplifying signal
      interpretation and delivery. This study evaluates in vivo relevance of a hybrid
      peripheral nervous system interface consisting of biological acellular muscle
      scaffolds made electrically conductive using poly(3,4-ethylenedioxythiophene).
      METHODS: Peripheral nervous system interfaces were tested in vivo using the rat
      hind-limb conduction-gap model for motor (peroneal) and sensory (sural) nerves.
      Experimental groups included acellular muscle, iron(III) chloride-treated
      acellular muscle, and poly(3,4-ethylenedioxythiophene) polymerized on acellular
      muscle, each compared with intact nerve, autogenous nerve graft, and empty
      (nonreconstructed) nerve gap controls (n=5 for each). Interface lengths tested
      included 0, 5, 10, and 20 mm. Immediately following implantation, the interface
      underwent electrophysiologic characterization in vivo using nerve conduction
      studies, compound muscle action potentials, and antidromic sensory nerve action
      potentials. RESULTS: Both efferent and afferent electrophysiology demonstrates
      acellular muscle-poly(3,4-ethylenedioxythiophene) interfaces conduct physiologic
      action potentials across nerve conduction gaps of at least 20 mm with amplitude
      and latency not differing from intact nerve or nerve grafts, with the exception
      of increased velocity in the acellular muscle-poly(3,4-ethylenedioxythiophene)
      interfaces. CONCLUSIONS: Nonmetallic, biosynthetic acellular muscle-poly(3,4
      ethylenedioxythiophene) peripheral nervous system interfaces both sense and
      stimulate physiologically relevant efferent and afferent action potentials in
      vivo. This demonstrates their relevance not only as a nerve-electronic coupling
      device capable of reaching the long-sought goal of closed-loop neural control of
      a prosthetic limb, but also in a multitude of other bioelectrical applications.

PMID- 20700081
TI  - Off-label use of bone morphogenetic proteins in the United States using
      administrative data.
AB  - STUDY DESIGN: Epidemiological study using national administrative data.
      OBJECTIVE: To evaluate the temporal trends in on-label and off-label bone
      morphogenetic protein (BMP) usage in primary and revision spine fusion by spine
      region and surgical approach, and nonspine applications in the United States from
      2002 to 2007. SUMMARY OF BACKGROUND DATA: The prevalence of BMP usage for spine
      fusion has been on the rise, but its use has not been stratified by surgical
      approach, particularly for lumbar fusion where it has only been Food And Drug
      Administration-approved for anterior lumbar interbody fusion (ALIF). METHODS: The
      prevalence of BMP usage in the United States was evaluated using the Nationwide
      Inpatient Sample between October 1, 2002 and December 31, 2007. The Nationwide
      Inpatient Sample is the single largest all-payer inpatient care database in the
      United States. The principal procedure associated with BMP use was determined,
      and the prevalence of BMP use was calculated for various population subgroups.
      RESULTS: A total of 340,251 inpatient procedures with BMP usage were identified.
      Between 2003 and 2007, the annual number of procedures involving BMP increased by
      4.3-fold from 23,900 to 103,194. Spine fusion accounted for the vast majority
      (92.8%) of principal procedures with BMP. The predominant use of BMP was in
      primary posterior lumbar interbody fusion or transforaminal lumbar interbody
      fusion (PLIF/TLIF) (30.0%), followed by primary posterolateral spine fusion
      (20.4%), primary ALIF (16.6%), primary cervical fusions (13.6%), and primary
      thoracolumbar fusions (3.9%). Of primary ALIF with BMP, 19.3% did not involve the
      implantation of an interbody device. CONCLUSION: At least 85% of principal
      procedures using BMP were for off-label applications. With uncertainty regarding
      the risks of using BMP in certain off-label applications, further research will
      be needed to better define the appropriate indications. Our study also
      demonstrates that disparities in the differential rates of BMP use exist in the
      spine fusion population.

PMID- 20700082
TI  - Effect of increasing implant height on lumbar spine kinematics and foraminal size
      using the ProDisc-L prosthesis.
AB  - STUDY DESIGN: A biomechanical study using human lumbar spines. OBJECTIVE: To test
      the hypotheses that with increasing implant height (1) the range of motion (ROM)
      of the implanted segment will decrease, (2) the segmental lordosis will increase,
      and (3) the size of the neural foramens will increase. SUMMARY OF BACKGROUND
      DATA: Little is known about the effects of the implant height on the segmental
      motion and foraminal size at the implanted level. METHODS: Seven human lumbar
      spines (age, 54.4+/-11.4 years; L1-sacrum) were tested intact, and after
      discectomy at L4-L5 and sequential insertion of ProDisc-L implants (Synthes
      Spine, Paoli, PA) of increasing heights (10, 12, and 14 mm). The specimens were
      tested in flexion (8 Nm) and extension (-6 Nm) with a 400 N follower preload as
      well as in lateral bending (+/-6 Nm) and axial rotation (+/-5 Nm) without
      preload. Three-dimensional motions were measured at L4-L5. Foraminal sizes at L4
      L5 were measured in the specimen's neutral posture under a 400 N preload for the
      intact spine and after each implantation using finely graded cylindrical probes.
      Segmental lordosis was measured in the specimen's neutral posture under a 400 N
      preload by analyzing digital fluoroscopic images. Effects of implant height on
      the kinematics, foraminal size, and segmental lordosis were assessed using paired
      comparisons with Bonferroni correction. RESULTS: Increasing implant height from
      10 mm to 14 mm caused a significant decrease (P<0.05) in segmental ROM by up to
      37%+/-21% in flexion/extension, 33%+/-18% in lateral bending, and 29%+/-28% in
      axial rotation. Increasing implant height also produced a significant increase in
      segmental lordosis (P<0.05): from 9.7 degrees+/-2.9 degrees at 10 mm, to 16.1
      degrees+/-5.1 degrees at 14 mm. The increase in foraminal size, while
      significant, was only 4.6%+/-3.2% when comparing 10 mm to 14 mm implants.
      CONCLUSION: These results suggest that a smaller implant height should be
      selected to optimize the ROM of the implanted segment and maintain sagittal
      balance.

PMID- 20700083
TI  - A new thoracic reconstruction technique "transforaminal thoracic interbody
      fusion": a preliminary report of clinical outcomes.
AB  - STUDY DESIGN: A preliminary clinical study. OBJECTIVE: The purpose of this study
      was to introduce a new reconstructive procedure called transforaminal thoracic
      interbody fusion (TTIF) for thoracic spine lesions and to evaluate its
      preliminary surgical outcomes. SUMMARY OF BACKGROUND DATA: Transforaminal lumbar
      interbody fusion, which was originally reported as unilateral posterior lumbar
      interbody fusion, has become a widely used minimally invasive technique. However,
      such reconstructive procedures have not been reported for the thoracic spine.
      METHODS: Ten patients with thoracic spine lesions associated with neurologic
      deficits were included in this study (6 males, 4 females; mean age, 53 years).
      Thoracic spine lesions included thoracic disc herniation, spinal trauma, spinal
      tumor, and arachnoid cyst. We investigated surgical complications and clinical
      outcomes such as operative time, blood loss, and sagittal alignment. Bony fusion
      was assessed using plain radiographs and computed tomography scans. RESULTS:
      Lesion level was at T11-T12 in 4 cases and T12-L1 in 3, while it was at T7-T9, T9
      T11, and T10-T11 in 1 case each. The mean operative time was 192 minutes, and the
      mean operative bleeding was 588 mL. All patients ambulated within 2 days after
      surgery. The mean follow-up period was 18.4 months (range, 12-44 months).
      Preoperative and postoperative local sagittal alignments (kyphotic angles) were
      12.9 degrees and 7.0 degrees . Fusion was observed in all cases. There were no
      serious complications such as neurologic deficit or infection. CONCLUSION: TTIF
      provides for safe interbody fusion and 270 degrees of decompression using a
      single posterior approach. TTIF is a useful method for reconstructing thoracic
      spine lesions associated with neurologic deficits.

PMID- 20700084
TI  - Minimal clinically important difference.

PMID- 20700085
TI  - Comparison of methods of measuring active cervical range of motion.
AB  - STUDY DESIGN: Experimental study. Cervical range of motion (CROM) was measured
      using different clinical methods. OBJECTIVE: To compare the reliability and
      accuracy of visual estimation, tape measurement, and the universal goniometer
      (UG) with that of the CROM goniometer in measuring active CROM in healthy
      volunteers. The secondary objective was to identify the single neck movement that
      best represents overall range of motion. SUMMARY OF BACKGROUND DATA: Neck
      movement is affected by pathology in the spine and shoulder. A reliable and
      accurate measurement of neck movement is required to quantify injury, recovery,
      and disability. Various methods of measuring neck movement have been described of
      which radiography remains the accepted reference standard. However, radiography
      is impractical for routine clinical assessment. Visual estimation, tape
      measurement, and the UG are convenient alternatives. To date, the accuracy and
      reliability of these methods have not been compared in healthy subjects, and the
      single neck movement that best reflects overall range has not yet been
      identified. METHODS: Active cervical flexion, extension, right and left lateral
      flexion and rotation were measured in 100 healthy volunteers. Visual estimation,
      tape measurement between fixed landmarks, and the UG aligned on fixed and
      anatomic landmarks were compared with the CROM goniometer, which was used as the
      reference standard. RESULTS: Compared with the CROM goniometer, the UG aligned on
      fixed landmarks was the most accurate method, followed by the UG on anatomic
      landmarks. The reliability of the UG was between substantial and perfect. Visual
      estimation was reproducible but measured range of movement inaccurately. Tape
      measurement was inaccurate. Extension best reflected overall range. CONCLUSION:
      The UG aligned on a fixed landmark is most reliable method of measuring neck
      movement clinically. Where range must be quickly assessed, extension should be
      measured.

PMID- 20700086
TI  - Validity of a quantitative clinical measurement tool of trunk posture in
      idiopathic scoliosis.
AB  - STUDY DESIGN: Concurrent validity between postural indices obtained from digital
      photographs (two-dimensional [2D]), surface topography imaging (three-dimensional
      [3D]), and radiographs. OBJECTIVE: To assess the validity of a quantitative
      clinical postural assessment tool of the trunk based on photographs (2D) as
      compared to a surface topography system (3D) as well as indices calculated from
      radiographs. SUMMARY OF BACKGROUND DATA: To monitor progression of scoliosis or
      change in posture over time in young persons with idiopathic scoliosis (IS),
      noninvasive and nonionizing methods are recommended. In a clinical setting,
      posture can be quite easily assessed by calculating key postural indices from
      photographs. METHODS: Quantitative postural indices of 70 subjects aged 10 to 20
      years old with IS (Cobb angle, 15 degrees -60 degrees) were measured from
      photographs and from 3D trunk surface images taken in the standing position.
      Shoulder, scapula, trunk list, pelvis, scoliosis, and waist angles indices were
      calculated with specially designed software. Frontal and sagittal Cobb angles and
      trunk list were also calculated on radiographs. The Pearson correlation
      coefficients (r) was used to estimate concurrent validity of the 2D clinical
      postural tool of the trunk with indices extracted from the 3D system and with
      those obtained from radiographs. RESULTS: The correlation between 2D and 3D
      indices was good to excellent for shoulder, pelvis, trunk list, and thoracic
      scoliosis (0.81>r<0.97; P<0.01) but fair to moderate for thoracic kyphosis,
      lumbar lordosis, and thoracolumbar or lumbar scoliosis (0.30>r<0.56; P<0.05). The
      correlation between 2D and radiograph spinal indices was fair to good (-0.33 to 
      0.80 with Cobb angles and 0.76 for trunk list; P<0.05). CONCLUSION: This tool
      will facilitate clinical practice by monitoring trunk posture among persons with
      IS. Further, it may contribute to a reduction in the use of radiographs to
      monitor scoliosis progression.

PMID- 20700087
TI  - Adaptation of torso movement strategies in persons with spinal cord injury or low
      back pain.
AB  - STUDY DESIGN: Controlled laboratory study. Statistical regression and between
      group comparisons. OBJECTIVE: To characterize functional limitation and adaptive
      strategies in seated manual transport tasks for spinal cord injury (SCI), low
      back pain (LBP), and control participants. SUMMARY OF BACKGROUND DATA: People
      with SCI are known to have adapted electromyographic activities and slow hand
      movement velocity, while those with LBP have reduced range of motion and lumbar
      joint contribution. However, their resultant outcome in torso movements has not
      been systematically quantified. METHODS: Seated participants performed either 2-
      or 1-handed loaded transports to 1 of 6 targets 49 cm above the hip-point, at 0
      degrees, 45 degrees, and 90 degrees azimuths, at close and far distance. Three
      dimensional torso movements were modeled by combinations of B-spine base
      functions. RESULTS: The SCI and LBP participants exhibit smaller torso flexion
      and axial rotation than control participants. The SCI participants tend to move
      the torso away from the target to maintain upper body balance. These differences
      among groups are significantly reduced in the 1-handed transport condition and/or
      transports to the frontal target. CONCLUSION: The movement patterns suggest that
      SCI participants may have adapted torso movement strategies to compensate for the
      limited control of upper body balance, while LBP participants may limit torso
      motion to avoid pain.

PMID- 20700088
TI  - Safety and efficacy of drug-eluting stents compared with bare metal stents in ST
      elevation myocardial infarction.
AB  - Drug-eluting stents (DES) reduce restenosis and the need for repeat
      revascularization, but patients with ST-segment elevation myocardial infarction
      (STEMI) were excluded from many of the trials that established the safety and
      efficacy of DES. Because of the unstable nature of lesions associated with STEMI,
      these patients are considered high risk, and often experience higher rates of
      adverse events. There is concern that DES may increase the risk of stent
      thrombosis, particularly late and very late stent thrombosis, in STEMI patients.
      Evidence also suggests that although DES reduce target vessel revascularization,
      this benefit may be lost after extended follow-up due to procedures necessitated
      by increased stent thrombosis. Several randomized trials, meta-analyses, and
      registry studies have been conducted to compare DES with bare metal stents in
      patients with STEMI, but many of the studies are not large scale and the length
      of follow-up has been limited in duration. This review summarizes the data
      comparing DES with bare metal stents in patients with STEMI.

PMID- 20700089
TI  - Management of atrial fibrillation: focus on catheter-based ablation.
AB  - Atrial fibrillation (AF) contributes to considerable morbidity, with increasing
      risk of stroke, complications from anticoagulation, and exacerbation of heart
      failure. AF ablation has become a commonly performed procedure in many hospitals
      as the procedural techniques evolve rapidly with improved success. Here we
      discuss the interventional options of catheter-based AF ablation for rhythm
      control, which offers the benefit of mortality reduction associated with normal
      sinus rhythm but without medication complications.

PMID- 20700090
TI  - Recognition of noncardiac findings on cardiac computed tomography examination.
AB  - Multislice computed tomography (CT) is rapidly emerging as a novel technique for
      the evaluation of coronary artery disease. It is anticipated that with increasing
      acceptance of this imaging technique, CT for calcium scores and CT angiography
      will be performed in ever greater numbers. Thus, it is all but inevitable that
      clinicians will stumble upon incidental findings given the sheer number of vital
      organs and blood vessels that are imaged in the field of view. This article
      reviews the literature on incidental findings on cardiac CT with a focus on
      pulmonary nodules, ethical aspects of following up such findings, and cost
      implications.

PMID- 20700091
TI  - Left ventricular noncompaction cardiomyopathy: what do we know?
AB  - Noncompaction is a rare and primary genetic cardiomyopathy affecting the left
      ventricle. The diagnosis is usually established by echocardiography, or, less
      frequently, by left ventriculography. Cardiac magnetic resonance and
      electrocardiography-gated multi-detector computed tomography are evolving
      noninvasive modalities to image cardiac structures, and have the utility to
      detect noncompacted myocardium. Estimates of the frequency and incidence of left
      ventricular noncompaction (LVNC) are limited because of the controversy over
      whether LVNC is a discrete disease entity. There is considerable overlap with
      dilated cardiomyopathy, apical hypertrophy, and hypertrophic cardiomyopathy.
      Symptoms, diagnosis, and prognosis are variable because of the heterogeneous
      nature of these diseases, making treatment often empirical and mimicking the
      treatment of other cardiomyopathies. However, there are management issues that
      should be addressed in each patient with LVNC, including genetic testing and
      family screening, the need for implantable cardioverter defibrillator placement,
      the role of anticoagulation in prevention of thromboembolic complications, and
      prescriptions/restrictions for implementation of physical activity.

PMID- 20700092
TI  - Accountable care organizations and cardiology practice--a wave of the future?

PMID- 20700093
TI  - Knowledge assessment for UK cardiology trainees.

PMID- 20700095
TI  - Unstable angina in a patient with anomalous origin of the left main coronary
      artery from the right sinus of Valsalva.
AB  - Anomalous coronary arteries are rare. Although most are not clinically
      significant, the most clinically important coronary anomaly is origin of the left
      main coronary artery from the right sinus of Valsalva, which can be associated
      with sudden death. We present a case of a 37-year-old man with unstable angina
      who underwent cardiac catheterization and was found to have this type of anomaly,
      which was later confirmed by coronary computed tomography angiography. Diagnosis
      and management of patients with this coronary anomaly are discussed.

PMID- 20700096
TI  - News and views from the literature. Antiplatelet therapy. Ticagrelor in acute
      coronary syndrome: a new frontier in platelet inhibition.

PMID- 20700097
TI  - Integration of the clinical laboratory in cardiovascular medicine.

PMID- 20700098
TI  - Differential diagnosis and overlap of acute chest discomfort and dyspnea in the
      emergency department.
AB  - Acute chest discomfort and dyspnea are 2 of the most common nontraumatic symptoms
      that prompt emergency department evaluations in the United States. The overlap
      between these presenting symptoms is considerable. In addition, each symptom
      calls for a broad differential diagnosis that requires rapid refinement according
      to details in the history, physical examination, blood biomarkers, and
      radiographic evaluation. This article highlights the epidemiology and the
      evidence supporting critical decision making, which makes judicious use of the
      clinical laboratory and diagnostic radiology in the evaluation of the acutely ill
      patient with chest discomfort and dyspnea.

PMID- 20700099
TI  - Natriuretic peptides in the prognosis and management of acute coronary syndromes.
AB  - Over the past decade, an evidence base has accumulated to support natriuretic
      peptide (NP) testing for diagnosis, risk assessment, and therapeutic monitoring
      and guidance of patients with heart failure. Investigators have also explored
      multiple other potential uses for these tests, including risk assessment of
      patients with suspected acute coronary syndromes (ACS). This article discusses
      the utility of NPs in the diagnosis and management of patients with ACS.

PMID- 20700100
TI  - Capturing the pathophysiology of acute coronary syndromes with circulating
      biomarkers.
AB  - There have been considerable advances in the evaluation of suspected acute
      coronary syndromes (ACS): sophistication of the clinical examination,
      electrocardiography, risk prediction scores, multiple blood biomarkers, and rapid
      cardiovascular imaging. Integration of information remains a formidable challenge
      for the physician in the setting of time-sensitive clinical decision making. In
      addition to conventional panels of biomarkers, there are novel entities that may
      be able to signal different stages of the acute event, including plaque
      disruption, atherothrombosis, ischemic damage, tissue hypoxia, and oxidative
      stress. The natriuretic peptides are normal myocyte products that reflect
      myocardial tissue response to neurohormonal and mechanical forces that rapidly
      change during an ACS event. This article summarizes major advancements in the
      integrative use of multiple blood biomarkers and cardiovascular imaging in the
      diagnosis, prognosis, and management of ACS.

PMID- 20700101
TI  - Cardiac computed tomography in the rapid evaluation of acute cardiac emergencies.
AB  - Approximately 6 million patients are evaluated annually in US emergency
      departments for acute chest pain. The delineation of the presence or absence of
      acute coronary syndromes in these patients must be accurate and efficient in
      order to prevent missed diagnoses. Coronary computed tomography angiography has
      great promise as a tool to expedite the triage of patients with acute chest pain
      to early discharge or further inpatient diagnosis and treatment.

PMID- 20700102
TI  - Time to treatment and acute coronary syndromes: bridging the gap in rapid
      decision making.
AB  - The role of cardiac biomarkers in the diagnosis, risk stratification, and
      treatment of patients with chest pain and suspected acute coronary syndromes
      (ACS) has continued to evolve. Although it is clear that troponin (Tn)
      measurement provides independent prognostic information in patients with
      suspected ACS, it is less well established that early B-type natriuretic peptide
      (BNP) measurement provides additional incremental prognostic information above
      and beyond electrocardiography and Tn measurement. It is useful to identify
      patients at high risk for adverse events through measurement of Tn and BNP levels
      so that timely treatment decisions can be made.

PMID- 20700103
TI  - An evidence-based algorithm for the use of B-type natriuretic testing in acute
      coronary syndromes.
AB  - Measurable B-type natriuretic peptides (BNPs), which are largely produced by the
      left ventricle, include BNP and N-terminal prohormone BNP (NT-proBNP). These
      proteins are released by cardiomyocytes in response to wall tension and
      neurohumoral signals, and are established tools in the diagnosis and prognosis of
      heart failure (HF). We identified 32 articles for entry into evidence tables that
      presented original data on BNP and/or NT-proBNP in more than 100 patients with
      acute coronary syndromes (ACS) presenting with chest discomfort with or without
      dyspnea. Natriuretic peptide (NP) elevation was associated with older age, female
      sex, hypertension, diabetes, prior HF, prior ischemic heart disease, and reduced
      renal function. Clinical correlates of elevated blood NP levels included left
      main or 3-vessel coronary disease, lipid-rich plaques with large necrotic cores
      in proximal locations, large zones of myocardial ischemia or infarction, no
      reflow and impaired perfusion after percutaneous intervention, reduced left
      ventricular ejection fraction, higher Killip classification, and the development
      of cardiogenic shock. All studies indicated that after adjustment for baseline
      predictors and clinical risk scores, elevated NP concentrations were
      independently predictive of the development of HF and all-cause mortality. In
      contrast, studies did not consistently demonstrate that NPs were predictive of
      myocardial infarction and rehospitalization for ACS. In addition to baseline
      measurement, there is consensus that repeat testing at 4 to 12 weeks and 6 to 12
      months in follow-up is helpful in the anticipation of late cardiac sequelae and
      may assist in assessing prognosis and guiding management.

PMID- 20700104
TI  - Metabolic regulation of Drosophila apoptosis through inhibitory phosphorylation
      of Dronc.
AB  - Apoptosis ensures tissue homeostasis in response to developmental cues or
      cellular damage. Recently reported genome-wide RNAi screens have suggested that
      several metabolic regulators can modulate caspase activation in Drosophila. Here,
      we establish a previously unrecognized link between metabolism and Drosophila
      apoptosis by showing that cellular NADPH levels modulate the initiator caspase
      Dronc through its phosphorylation at S130. Depletion of NADPH removed this
      inhibitory phosphorylation, resulting in the activation of Dronc and subsequent
      cell death. Conversely, upregulation of NADPH prevented Dronc-mediated apoptosis
      upon DIAP1 RNAi or cycloheximide treatment. Furthermore, this CaMKII-mediated
      phosphorylation of Dronc hindered Dronc activation, but not its catalytic
      activity. Blockade of NADPH production aggravated the death-inducing activity of
      Dronc in specific neurons, but not in the photoreceptor cells of the eyes of
      transgenic flies; similarly, non-phosphorylatable Dronc was more potent than wild
      type in triggering specific neuronal apoptosis. Our observations reveal a novel
      regulatory circuitry in Drosophila apoptosis, and, as NADPH levels are elevated
      in cancer cells, also provide a genetic model to understand aberrations in cancer
      cell apoptosis resulting from metabolic alterations.

PMID- 20700105
TI  - alpha-Catulin CTN-1 is required for BK channel subcellular localization in C.
      elegans body-wall muscle cells.
AB  - The BK channel, a voltage- and Ca(2+)-gated large-conductance potassium channel
      with many important functions, is often localized at specific subcellular
      domains. Although proper subcellular localization is likely a prerequisite for
      the channel to perform its physiological functions, little is known about the
      molecular basis of localization. Here, we show that CTN-1, a homologue of
      mammalian alpha-catulin, is required for subcellular localization of SLO-1, the
      Caenorhabditis elegans BK channel alpha-subunit, in body-wall muscle cells. CTN-1
      was identified in a genetic screen for mutants that suppressed a lethargic
      phenotype caused by expressing a gain-of-function (gf) isoform of SLO-1. In body
      wall muscle cells, CTN-1 coclusters with SLO-1 at regions of dense bodies, which
      are Z-disk analogs of mammalian skeletal muscle. In ctn-1 loss-of-function (lf)
      mutants, SLO-1 was mislocalized in body-wall muscle but its transcription and
      protein level were unchanged. Targeted rescue of ctn-1(lf) in muscle was
      sufficient to reinstate the lethargic phenotype in slo-1(gf);ctn-1(lf). These
      results suggest that CTN-1 plays an important role in BK channel function by
      mediating channel subcellular localization.

PMID- 20700106
TI  - Dynamin GTPase regulation is altered by PH domain mutations found in
      centronuclear myopathy patients.
AB  - The large GTPase dynamin has an important membrane scission function in receptor
      mediated endocytosis and other cellular processes. Self-assembly on
      phosphoinositide-containing membranes stimulates dynamin GTPase activity, which
      is crucial for its function. Although the pleckstrin-homology (PH) domain is
      known to mediate phosphoinositide binding by dynamin, it remains unclear how this
      promotes activation. Here, we describe studies of dynamin PH domain mutations
      found in centronuclear myopathy (CNM) that increase dynamin's GTPase activity
      without altering phosphoinositide binding. CNM mutations in the PH domain C
      terminal alpha-helix appear to cause conformational changes in dynamin that alter
      control of the GTP hydrolysis cycle. These mutations either 'sensitize' dynamin
      to lipid stimulation or elevate basal GTPase rates by promoting self-assembly and
      thus rendering dynamin no longer lipid responsive. We also describe a low
      resolution structure of dimeric dynamin from small-angle X-ray scattering that
      reveals conformational changes induced by CNM mutations, and defines requirements
      for domain rearrangement upon dynamin self-assembly at membrane surfaces. Our
      data suggest that changes in the PH domain may couple lipid binding to dynamin
      GTPase activation at sites of vesicle invagination.

PMID- 20700107
TI  - Personalized versus evidence-based medicine with PET-based imaging.
AB  - In this Perspective the feasibility, scope and impact of integrating PET-based
      personalized medicine into the evidence-based clinical practice of oncology is
      discussed. The basic concepts of 'evidence-based medicine' and 'personalized
      medicine' at times seem contradictory; however, I will discuss, with specific
      clinical situations as examples, a synergistic and probably incremental link
      between the two and propose that the result of such integration will ultimately
      improve patient management. Tailoring therapeutic approaches and regimens by
      molecular imaging, with PET at its forefront, would enable disease management at
      the individual level and this modification would hopefully further strengthen the
      evidence-based approach in oncology.

PMID- 20700108
TI  - Making the best of PARP inhibitors in ovarian cancer.
AB  - Drugs that inhibit the enzyme poly(ADP-ribose)polymerase (PARP) are showing
      considerable promise for the treatment of cancers that have mutations in the
      BRCA1 or BRCA2 tumor suppressors. This therapeutic approach exploits a synthetic
      lethal strategy to target the specific DNA repair pathway in these tumors. High
      grade ovarian cancers have a generally poor prognosis, and accumulating evidence
      suggests that mutations in BRCA1 or BRCA2, or silencing of BRCA1 by promoter
      methylation, may be common in this disease. Here, we consider how the potential
      benefit of PARP inhibitors might be maximized in ovarian cancer. We suggest that
      it will be crucial to explore novel therapeutic trial strategies and drug
      combinations, and incorporate robust biomarkers predictive of response if these
      drugs are to reach their full potential.

PMID- 20700109
TI  - Proteasome inhibitors enhance gene delivery by AAV virus vectors expressing large
      genomes in hemophilia mouse and dog models: a strategy for broad clinical
      application.
AB  - Delivery of genes that are larger than the wild-type adeno-associated virus (AAV)
      4,681 nucleotide genome is inefficient using AAV vectors. We previously
      demonstrated in vitro that concurrent proteasome inhibitor (PI) treatment
      improves transduction by AAV vectors encoding oversized transgenes. In this
      study, an AAV vector with a 5.6 kilobase (kb) factor VIII expression cassette was
      used to test the effect of an US Food and Drug Administration-approved PI
      (bortezomib) treatment concurrent with vector delivery in vivo. Intrahepatic
      vector delivery resulted in factor VIII expression that persisted for >1 year in
      hemophilia mice. Single-dose bortezomib given with AAV2 or AAV8 factor VIII
      vector enhanced expression on average ~600 and ~300%, respectively. Moreover,
      coadministration of AAV8.canineFVIII (1 * 10(13) vg/kg) and bortezomib in
      hemophilia A dogs (n = 4) resulted in normalization of the whole blood clotting
      time (WBCT) and 90% reduction in hemorrhages for >32 months compared to untreated
      hemophilia A dogs (n = 3) or dogs administered vector alone (n = 3).
      Demonstration of long-term phenotypic correction of hemophilia A dogs with
      combination adjuvant bortezomib and AAV vector expressing the oversized transgene
      establishes preclinical studies that support testing in humans and provides a
      working paradigm to facilitate a significant expansion of therapeutic targets for
      human gene therapy.

PMID- 20700110
TI  - POD nanoparticles expressing GDNF provide structural and functional rescue of
      light-induced retinal degeneration in an adult mouse.
AB  - Peptide for ocular delivery (POD) is a novel cationic cell-penetrating peptide
      (CPP) which, when conjugated with polyethylene glycol (PEG-POD), can deliver
      plasmid DNA to the retinal pigment epithelium (RPE) of adult murine retina. PEG
      POD nanoparticles containing an expression cassette for glial cell line-derived
      neurotrophic factor (PEG-POD~GDNF) were investigated for their ability to inhibit
      light-induced photoreceptor apoptosis. PEG-POD~GDNF, control nanoparticles, or
      buffer were injected into the subretinal space of adult murine retina and retinal
      degeneration induced by blue light. Animals injected with PEG-POD~GDNF showed a
      significant reduction (3.9-7.7 fold) in apoptosis relative to control-injected
      animals. The thickness of the outer nuclear layer (ONL) of the superior retina of
      PEG-POD~GDNF-injected eyes was significantly greater (23.6-39.3%) than control
      injected retina 14 days post-light treatment. PEG-POD~GDNF-injected eyes showed a
      27-39% greater functional response relative to controls, as measured by
      electroretinogram (ERG) 7 days post-light treatment. This is one of only two
      studies demonstrating histological and functional rescue of a mouse model of
      retinal degeneration following nonviral administration of a transgene into adult
      retina. Although rescue is short lived for clinical application, this study
      represents an important step in the development of nonviral gene therapy for
      retinal diseases.

PMID- 20700111
TI  - Blocking the myostatin signal with a dominant negative receptor improves the
      success of human myoblast transplantation in dystrophic mice.
AB  - Duchenne muscular dystrophy (DMD) is a recessive disease caused by a dystrophin
      gene mutation. Myoblast transplantation permits to introduce the dystrophin gene
      in dystrophic muscle fibers. However, the success of this approach is reduced by
      the short duration of the regeneration following the transplantation, which
      reduces the number of hybrid fibers. Myostatin (MSTN) is a negative regulator of
      skeletal muscle development and responsible for limiting regeneration. It binds
      with high affinity to the activin type IIB receptor (ActRIIB). Our aim was to
      verify whether the success of the myoblast transplantation is enhanced by
      blocking the MSTN signal with expression of a dominant negative mutant of ActRIIB
      (dnActRIIB). In vitro, blocking MSTN activity with a lentivirus carrying
      dnActRIIB increased proliferation and fusion of human myoblasts because MSTN
      regulates the expression of several myogenic regulatory factors. In vivo,
      myoblasts infected with the dnActRIIB lentivirus were transplanted in
      immunodeficient dystrophic mice. Dystrophin immunostaining of tibialis anterior
      (TA) cross-sections of these mice 1 month post-transplantation revealed more
      human dystrophin-positive myofibers following the transplantation of dnActRIIB
      myoblasts than of control myoblasts. Thus, blocking the MSTN signal with
      dnActRIIB improved the success of myoblast transplantation by increasing the
      myoblast proliferation and fusion and changed the expression of myogenic
      regulatory factors.

PMID- 20700112
TI  - Selectivity of oncolytic viral replication prevents antiviral immune response and
      toxicity, but does not improve antitumoral immunity.
AB  - Oncolytic infection elicits antitumoral immunity, but the impact of tumor
      selective replication on the balance between antiviral and antitumoral immune
      responses has not yet been investigated. To address this question, we constructed
      the highly tumor-selective adenovirus Ad-p53T whose replication in target tumor
      cells is governed by aberrant telomerase activity and transcriptional p53
      dysfunction. Telomerase-dependent or nonselective adenoviruses were constructed
      as isogenic controls. Following infection of mice with the nonselective
      adenovirus, viral DNA and mRNA levels correlated with strong stimulation of
      innate immune response genes and severe liver toxicity, whereas telomerase-/p53
      specific replication did not trigger innate immunity and prevented liver damage.
      Compared to telomerase-dependent or unselective viral replication, telomerase
      /p53-specific virotherapy significantly decreased antiviral CD8-specific immune
      responses and antiviral cytotoxicity in vivo. Consistent with our hypothesis,
      telomerase-selective replication led to intermediate results in these
      experiments. Remarkably, all viruses efficiently lysed tumors and induced a
      therapeutically effective tumor-directed CD8 cytotoxicity. In immunocompetent
      mice with extended lung metastases burden, treatment of subcutaneous primary
      tumors with Ad-p53T significantly prolonged survival by inhibition of lung
      metastases, whereas unselective viral replication resulted in death by liver
      failure. In summary, the degree of tumor selectivity of viral replication
      marginally influences antitumoral immune responses, but is a major determinant of
      antivector immunity and systemic toxicity.

PMID- 20700113
TI  - Functional rescue of dystrophin-deficient mdx mice by a chimeric peptide-PMO.
AB  - Splice modulation using antisense oligonucleotides (AOs) has been shown to yield
      targeted exon exclusion to restore the open reading frame and generate truncated
      but partially functional dystrophin protein. This has been successfully
      demonstrated in dystrophin-deficient mdx mice and in Duchenne muscular dystrophy
      (DMD) patients. However, DMD is a systemic disease; successful therapeutic
      exploitation of this approach will therefore depend on effective systemic
      delivery of AOs to all affected tissues. We have previously shown the potential
      of a muscle-specific/arginine-rich chimeric peptide-phosphorodiamidate morpholino
      (PMO) conjugate, but its long-term activity, optimized dosing regimen, capacity
      for functional correction and safety profile remain to be established. Here, we
      report the results of this chimeric peptide-PMO conjugate in the mdx mouse using
      low doses (3 and 6 mg/kg) administered via a 6 biweekly systemic intravenous
      injection protocol. We show 100% dystrophin-positive fibers and near complete
      correction of the dystrophin transcript defect in all peripheral muscle groups,
      with restoration of 50% dystrophin protein over 12 weeks, leading to correction
      of the DMD pathological phenotype and restoration of muscle function in the
      absence of detectable toxicity or immune response. Chimeric muscle-specific/cell
      penetrating peptides therefore represent highly promising agents for systemic
      delivery of splice-correcting PMO oligomers for DMD therapy.

PMID- 20700114
TI  - Sex differences in performance of fecal occult blood testing.
AB  - OBJECTIVES: Immunological and guaiac-based fecal occult blood tests (iFOBTs and
      gFOBTs) are widely used for early detection of colorectal cancer (CRC). We aimed
      to assess potential sex differences in performance of iFOBTs and gFOBT in the
      screening setting. METHODS: The sensitivity, specificity, and positive and
      negative predictive values for detection of advanced colorectal neoplasms (CRC or
      advanced adenoma) were assessed by sex for a range of cutpoints of a quantitative
      iFOBT (RIDASCREEN Hemoglobin), six qualitative iFOBTs, and a gFOBT (HemOccult)
      among 1,157 male and 1,167 female participants of the German screening
      colonoscopy program (mean age: 63.0 and 62.0 years, respectively). RESULTS: The
      prevalence of advanced colorectal neoplasms was much higher among men (13.5%)
      than among women (7.5%). At any cutpoint of the quantitative iFOBT, and for all
      qualitative iFOBTs and the gFOBT, the sensitivity and positive predictive value
      were substantially higher, and specificity and negative predictive value were
      substantially lower among men than among women. At the cutpoint of 2 MUg/g stool
      given by the manufacturer of the quantitative iFOBT, sensitivity, specificity,
      and the positive and negative predictive values were 47.6, 85.0, 33.0, and 91.3%
      among men, and 30.7, 89.5, 19.3, and 94.1% among women (P value for sex
      differences 0.001, 0.002, 0.004, and 0.019, respectively). Sex differences in
      predictive values were mostly explained by sex differences in the prevalence of
      advanced colorectal neoplasms. CONCLUSIONS: There are major sex differences in
      the performance of fecal occult blood testing, which might require careful
      attention in the interpretation of test results, and in the design, modeling, and
      evaluation of CRC screening strategies.

PMID- 20700115
TI  - Potential association between the oral tetracycline class of antimicrobials used
      to treat acne and inflammatory bowel disease.
AB  - OBJECTIVES: Previous studies have shown an association between isotretinoin and
      inflammatory bowel disease (IBD). The majority of patients prescribed
      isotretinoin for their acne are previously on an extended course of antibiotics.
      Therefore, it is important to consider antibiotic use as a confounding variable
      for the development of IBD. METHODS: We performed a retrospective cohort study
      using The Health Improvement Network database of the United Kingdom. We
      identified 94,487 individuals with acne who were followed up by a general
      practitioner for 406,294 person-years. RESULTS: >A prescription for minocycline
      was received by 24,085 individuals, for tetracycline/oxytetracycline by 38,603
      individuals, and doxycycline by 15,032 individuals. IBD was noted in 41
      individuals exposed to minocycline, 79 individuals exposed to
      tetracycline/oxytetracycline, 32 individuals exposed to doxycycline, and 55
      (0.11%) individuals not exposed to any of these antibiotics. The hazard ratio
      (HR) for developing IBD for any exposure to a tetracycline antibiotic was 1.39
      (1.02, 1.90). HRs for individual antibiotics were 1.19 (0.79, 1.79) for
      minocycline, 1.43 (1.02, 2.02) for tetracycline/oxytetracycline, and 1.63 (1.05,
      2.52) for doxycycline. For ulcerative colitis, the associations (HR) were 1.10
      (0.76, 1.82) for minocycline, 1.27 (0.78, 2.07) for tetracycline/oxytetracycline,
      and 1.06 (0.53, 2.13) for doxycycline. For Crohn's disease (CD), the associations
      (HR) were 1.28 (0.72, 2.30) for minocycline, 1.61 (0.995, 2.63) for
      tetracycline/oxytetracycline, and 2.25 (1.27 4.00) for doxycycline. CONCLUSIONS:
      Tetracycline class antibiotics, and particularly doxycycline use may be
      associated with the development of IBD, particularly CD. Potential confounding by
      previous doxycycline exposure should be considered when assessing whether
      treatment with other acne medications increases the risk of IBD.

PMID- 20700116
TI  - Peginterferon plus ribavirin and sustained virological response in HCV-related
      cirrhosis: outcomes and factors predicting response.
AB  - OBJECTIVES: Patients with hepatitis C virus (HCV) cirrhosis are difficult to
      treat and have a high risk of liver decompensation or hepatocellular carcinoma.
      We sought to identify factors that could predict treatment response. METHODS:
      Collaborating centers (n=26) provided data for patients (n=568) with HCV
      cirrhosis undergoing treatment with peginterferon-alpha plus ribavirin (RBV).
      Univariate and multivariate analyses were used to evaluate factors predicting
      treatment outcomes. RESULTS: Sustained viral response (SVR) in naive patients was
      30.7%, with no significant differences between centers. Median follow-up was 35
      months (range: 1-81). Factors predicting SVR were: non-genotype 1 (odds ratio
      (OR)=4.183; 95% confidence interval (CI): 2.353-7.438) overall dose and >=80% of
      the scheduled time of treatment (OR=3.177; 95% CI: 1.752-5.760); serum gamma
      glutamyl transpeptidase (GGT) <76 IU per ml (OR=4.092; 95% CI: 2.418-6.927);
      baseline viral load <6 * 10(5) (OR=2.597; 95% CI: 1.583-4.262); absence of
      ultrasound signs of portal hypertension (OR=2.067; 95% CI: 1.26-3.39). No patient
      with a HCV-RNA decline <1 log(10) at week 4 achieved SVR. Event-free survival at
      5 years was 91% in patients with SVR vs. 59% in non-responders (P<0.001). Overall
      survival in patients with SVR was 98% vs. 86% in non-responders (P=0.005).
      Independent factors predicting events were absence of SVR (hazard ratio
      (HR)=2.66; 95% CI: 1.32-5.54), baseline serum albumin <3.9 g per 100 ml (HR=3.06;
      95% CI: 1.81-5.15), presence of esophageal varices on endoscopy (HR=2.489; 95%
      CI: 1.546-4). Improved outcome was more evident in responders with less advanced
      disease at baseline. CONCLUSIONS: SVR can be achieved in approximately one-third
      of patients with HCV-related cirrhosis. SVR independently reduces the likelihood
      of clinical decompensation and improves survival.

PMID- 20700117
TI  - Outcomes of pregnancies fathered by inflammatory bowel disease patients exposed
      to thiopurines.
AB  - OBJECTIVES: Immunomodulators are used as maintenance treatment of inflammatory
      bowel disease (IBD). Data regarding their possible effects in the course of
      pregnancy when the father is exposed at the time of conception are limited.
      METHODS: To evaluate the outcomes of pregnancies of which the fathers were
      exposed to thiopurines at the time of conception. A series of male patients
      followed in seven IBD clinics in Madrid, Spain, was studied. Any exposure to
      thiopurines during the 3 months preceding conception was considered significant.
      Controls were pregnancies fathered by patients who either had never been treated
      with thiopurines or had interrupted them >3 months before conception. Statistical
      comparisons and multivariate analysis were carried out with the generalized
      estimating equations model. RESULTS: There were 46 conceptions in the exposed
      group (mercaptopurine 9, azathioprine 37) and 84 in the control group. In the
      exposed group, there were more Crohn's patients (82.6% vs. 53.6%), the duration
      of the disease was longer (median: 8 vs. 5 years), fathers were slightly older
      (mean: 34.2 vs. 32.7 years), and there were fewer patients on mesalamine (15.2%
      vs. 47.6%). Otherwise, baseline characteristics were similar in both groups.
      There were no significant differences regarding unsuccessful pregnancies-namely,
      spontaneous abortions, ectopic pregnancies, anembryonic pregnancies, or fetal
      deaths (10.9% exposed group vs. 13.1% control group; odds ratio (OR): 0.79,
      confidence interval (CI): 0.22-2.85), preterm births (4.3% vs. 2.4%; OR: 1.3, CI:
      0.22-7.61), low birth weight (6.5% vs. 6%; OR: 1.06, CI: 0.25-4.54), or
      congenital malformations (2.2% vs. 2.4%; OR: 0.82, CI: 0.08-9). No infant
      neoplasms were detected. The proportion of conceptions that needed >1 year to be
      achieved was higher in the exposed group, but this was not statistically
      significant (15.2% vs. 8.3%; OR: 1.92, CI: 0.54-6.88). Multivariate analysis was
      carried out for unsuccessful pregnancies and fertility impairment, and it showed
      that, although mesalamine exposure confounded the effect of the exposure to
      thiopurines on these outcomes, this effect was still nonsignificant
      (respectively, OR: 0.49, CI: 0.17-1.44; OR: 2.82, CI: 0.7-11.38). CONCLUSIONS:
      Our data do not support the practice of routinely recommending to male patients
      that they interrupt thiopurines when wanting to conceive.

PMID- 20700118
TI  - Neoadjuvant endocrine therapy in primary breast cancer: indications and use as a
      research tool.
AB  - Neoadjuvant endocrine therapy has been increasingly employed in clinical practice
      to improve surgical options for postmenopausal women with bulky hormone receptor
      positive breast cancer. Recent studies indicate that tumour response in this
      setting may predict long-term outcome of patients on adjuvant endocrine therapy,
      which argues for its broader application in treating hormone receptor-positive
      disease. From the research perspective, neoadjuvant endocrine therapy provides a
      unique opportunity for studies of endocrine responsiveness and the development of
      novel therapeutic agents.

PMID- 20700119
TI  - Prevalence and risk factors for esophageal squamous cell cancer and precursor
      lesions in Anyang, China: a population-based endoscopic survey.
AB  - BACKGROUND: The etiology of esophageal squamous cell cancer (ESCC) in high
      prevalence regions of China remains unclear. METHODS: Endoscopic biopsies were
      conducted among 7381 inhabitants aged from 25 to 65 of Anyang, China. RESULTS: In
      this study, 2.57, 0.20 and 0.16% of the participants had mild, moderate and
      severe squamous dysplasia, respectively; 0.19 and 0.08% showed squamous carcinoma
      in situ and invasive ESCC. Using deep well (depth >100 meters) as water source
      (odds ratio=0.72, 95% confidence interval: 0.54-0.96) was negatively associated
      with ESCC and its precursors, whereas tobacco and alcohol use were not
      significantly associated with ESCC. CONCLUSIONS: Water source and other factors
      in this region need further evaluation by longitudinal studies.

PMID- 20700120
TI  - The impact of CYP2D6-predicted phenotype on tamoxifen treatment outcome in
      patients with metastatic breast cancer.
AB  - BACKGROUND: Cytochrome P450 2D6 (CYP2D6) has a crucial role in the metabolic
      conversion of tamoxifen into the active metabolite endoxifen. In this cohort
      study, the effect of CYP2D6-predicted phenotype, defined as the combined effect
      of CYP2D6 genetic variation and concomitant use of CYP2D6-inhibiting medication,
      on time to breast cancer progression (TTP) and overall survival (OS) in women who
      use tamoxifen for metastatic breast cancer (MBC) was examined. METHODS: We
      selected patients treated with tamoxifen (40 mg per day) for hormone receptor
      positive MBC from whom a blood sample for pharmacogenetic analysis (CYP2D6*3, *4,
      *5, *6, *10 and *41) was available. Patient charts (n=102) were reviewed to
      assess TTP and OS, and to determine whether CYP2D6 inhibitors were prescribed
      during tamoxifen treatment. RESULTS: OS was significantly shorter in patients
      with a poor CYP2D6 metaboliser phenotype, compared with extensive metabolisers
      (HR=2.09; P=0.034; 95% CI: 1.06-4.12). Co-administration of CYP2D6 inhibitors
      alone was also associated with a worse OS (HR=3.55; P=0.002; 95% CI: 1.59-7.96)
      and TTP (HR=2.97; P=0.008; 95% CI: 1.33-6.67) compared with patients without
      CYP2D6 inhibitors. CONCLUSION: CYP2D6 phenotype is an important predictor of
      treatment outcome in women who are receiving tamoxifen for MBC. Co-administration
      of CYP2D6 inhibitors worsens treatment outcome of tamoxifen and should therefore
      be handled with care.

PMID- 20700121
TI  - Sex-specific exposure prevalence of established risk factors for oesophageal
      adenocarcinoma.
AB  - BACKGROUND: There is an unexplained male predominance in the incidence of
      oesophageal adenocarcinoma, and the sex-specific distribution of its risk factors
      in the general population is not known. METHODS: A random sample of Swedish
      citizens aged 40-79 years completed a questionnaire for assessment of the
      prevalence of five risk factors for oesophageal adenocarcinoma: reflux symptoms,
      body mass index, tobacco smoking habits, socioeconomic status, and use of non
      steroidal anti-inflammatory drugs (NSAIDs). Logistic regression was used to
      calculate odds ratios (ORs) with 95% confidence intervals (CIs) to evaluate the
      association of these risk factors, separately and combined, with male sex, with
      women as reference. RESULTS: Among 6969 invited people, 4906 (70.4%) completed
      the questionnaire. Adjusted prevalence estimates showed a negative association
      with male sex with regard to reflux disease (OR=0.70, 95% CI=0.58-0.84), whereas
      overweight (OR=1.98, 95% CI=1.72-2.27) and obesity (OR=1.22, 95% CI=1.01-1.47),
      previous smoking (OR=1.50, 95% CI=1.30-1.72), and no NSAID use (OR=1.35, 95%
      CI=1.15-1.49) were positively associated. CONCLUSIONS: Exposure to some but not
      all established risk factors for oesophageal adenocarcinoma seems to be more
      common in men than in women, but the differences are small and unlikely to
      explain the male predominance of this tumour.

PMID- 20700122
TI  - Molecular basis of chemosensitivity of platinum pre-treated ovarian cancer to
      chemotherapy.
AB  - BACKGROUND: Ovarian cancer shows considerable heterogeneity in its sensitivity to
      chemotherapy both clinically and in vitro. This study tested the hypothesis that
      the molecular basis of this difference lies within the known resistance
      mechanisms inherent to these patients' tumours. METHODS: The chemosensitivity of
      a series of 31 ovarian tumours, all previously treated with platinum-based
      chemotherapy, was assessed using the ATP-based tumour chemosensitivity assay (ATP
      TCA) and correlated with resistance gene expression measured by quantitative
      reverse-transcriptase polymerase chain reaction (qRT-PCR) in a TaqMan Array
      following extraction of mRNA from formalin-fixed paraffin-embedded tissue. The
      results were standardised against a housekeeping gene (PBGD), and assessed by
      multiple linear regression. RESULTS: Predictive multiple linear regression models
      were derived for four single agents (cisplatin, gemcitabine, topotecan, and
      treosulfan), and for the combinations of cisplatin+gemcitabine and
      treosulfan+gemcitabine. Particularly strong correlations were obtained for
      cisplatin, gemcitabine, topotecan, and treosulfan+gemcitabine. No individual gene
      expression showed direct correlation with activity in the ATP-TCA. Genes involved
      in DNA repair and apoptosis were strongly represented, with some drug pumps also
      involved. CONCLUSION: The chemosensitivity of ovarian cancer to drugs is related
      to the expression of genes involved in sensitivity and resistance mechanisms.

PMID- 20700123
TI  - miR-489 is a tumour-suppressive miRNA target PTPN11 in hypopharyngeal squamous
      cell carcinoma (HSCC).
AB  - BACKGROUND: Hypopharyngeal squamous cell carcinoma (HSCC) is an aggressive
      malignancy with one of the worst prognoses among all head and neck cancers.
      Greater understanding of the pertinent molecular oncogenic pathways could help
      improve diagnosis, therapy, and prevention of this disease. The aim of this study
      was to identify tumour-suppressive microRNAs (miRNAs), based on miRNA expression
      signatures from clinical HSCC specimens, and to predict their biological target
      genes. METHODS: Expression levels of 365 human mature miRNAs from 10 HSCC
      clinical samples were screened using stem-loop real-time quantitative PCR.
      Downregulated miRNAs were used in cell proliferation assays to identify a tumour
      suppressive miRNA. Genome-wide gene expression analyses were then performed to
      identify the target genes of the tumour-suppressive miRNA. RESULTS: Expression
      analysis identified 11 upregulated and 31 downregulated miRNAs. Gain-of-function
      analysis of the downregulated miRNAs revealed that miR-489 inhibited cell growth
      in all head and neck cancer cell lines examined. The gene PTPN11 coding for a
      cytoplasmic protein tyrosine phosphatase containing two Src Homology 2 domains
      was identified as a miR-489-targeted gene. Knockdown of PTPN11 resulted in the
      inhibition of cell proliferation in head and neck SCC cells. CONCLUSION:
      Identification of the tumour-suppressive miRNA miR-489 and its target, PTPN11,
      might provide new insights into the underlying molecular mechanisms of HSCC.

PMID- 20700124
TI  - hI-con1, a factor VII-IgGFc chimeric protein targeting tissue factor for
      immunotherapy of uterine serous papillary carcinoma.
AB  - BACKGROUND: Uterine serous papillary adenocarcinoma (USPC) is a highly aggressive
      variant of endometrial cancer. Human immuno-conjugate molecule (hI-con1) is an
      antibody-like molecule targeted against tissue factor (TF), composed of two human
      Factor VII (fVII) as the targeting domain, fused to human immunoglobulin (Ig) G1
      Fc as an effector domain. We evaluated hI-con1 potential activity against primary
      chemotherapy-resistant USPC cell lines expressing different levels of TF.
      METHODS: A total of 16 formalin-fixed, paraffin-embedded USPC samples were
      evaluated by immunohistochemistry (IHC) for TF expression. Six primary USPC cell
      lines, half of which overexpress the epidermal growth factor type II (HER2/neu)
      receptor at 3+ levels, were assessed by flow cytometry and real-time PCR for TF
      expression. Sensitivity to hI-con1-dependent cell-mediated cytotoxicity (IDCC)
      was evaluated in 5-hour-chromium release assays. Finally, to investigate the
      effect of interleukin-2 (IL-2) on IDCC, 5-h (51)Cr assays were also conducted in
      the presence of low doses of IL-2 (i.e., 50-100 IU ml(-1)). RESULTS: Cytoplasmic
      and/or membrane TF expression was observed in all 16 (100%) USPC samples tested
      by IHC, but not in normal endometrium. High expression of TF was found in 50%
      (three out of six) of the USPC cell lines tested by real-time PCR and flow
      cytometry when compared with normal endometrial cells (NECs; P<0.001). Uterine
      serous papillary adenocarcinoma cell lines overexpressing TF, regardless of their
      high or low HER2/neu expression, were highly sensitive to IDCC (mean killing+/
      s.d., 65.6+/-3.7%, range 57.5-77.0%, P<0.001), although negligible cytotoxicity
      against USPC was seen in the absence of hI-con1 or in the presence of Rituximab
      control antibody. The addition of low doses of IL-2 further increased the
      cytotoxic effect induced by hI-con1 against chemotherapy-resistant USPC.
      CONCLUSION: hI-con1 induces strong cytotoxicity against primary chemotherapy
      resistant USPC cell lines overexpressing TF. The hI-con1 may represent a novel
      therapeutic agent for the treatment of patients harbouring advanced, recurrent
      and/or metastatic USPC refractory to standard treatment modalities.

PMID- 20700125
TI  - Thymidine synthase, thymidine phosphorylase, and excision repair cross
      complementation group 1 expression as predictive markers of capecitabine plus
      cisplatin chemotherapy as first-line treatment for patients with advanced
      oesophageal squamous cell carcinoma.
AB  - BACKGROUND: Our purpose was to evaluate thymidine synthase (TS), thymidine
      phosphorylase (TP), and excision repair cross-complementation group 1 (ERCC1)
      expression as biomarkers for capecitabine and cisplatin (XP) combination
      chemotherapy in patients with metastatic oesophageal squamous cell cancer.
      METHOD: A total of 113 patients with metastatic oesophageal squamous cell cancer
      were treated with XP chemotherapy at the Samsung Medical Center between 2003 and
      2007, of whom 72 had available clinical data and paraffin blocks for
      immunohistochemistry of TS, TP, and ERCC1. RESULTS: The median age of the 72
      patients was 62 years. The overall response rate (RR) was 51.4%. The median
      progression-free survival (PFS) and overall survival (OS) were 4.2 and 12.0
      months, respectively. High expression of TS and TP was associated with a higher
      RR than was low expression of TS and TP (54.1 vs 40.5%, P=0.022). Strong ERCC1
      expression and a low TS score were identified as unfavourable independent risk
      factors for PFS (HR 10.71, 95% confidence interval (CI) 2.1-54.7, P=0.004 for
      strong ERCC1 expression; and HR 2.9, 95% CI 1.0-7.9, P=0.044 for low TS score).
      Strong ERCC1 expression was identified as an unfavourable independent risk factor
      for OS (HR 3.73, 95% CI 1.39-10.0, P=0.009). CONCLUSION: These data indicate that
      expression of TS, TP, and ERCC1 may be predictive markers for response and
      survival in patients with metastatic oesophageal squamous cell cancer receiving
      XP chemotherapy.

PMID- 20700126
TI  - In situ quantification of HER2-protein tyrosine kinase 6 (PTK6) protein-protein
      complexes in paraffin sections from breast cancer tissues.
AB  - BACKGROUND: Protein tyrosine kinase 6 (PTK6; breast tumour kinase) is
      overexpressed in up to 86% of the invasive breast cancers, and its association
      with the oncoprotein human epidermal growth factor receptor 2 (HER2) was shown in
      vitro by co-precipitation. Furthermore, expression of PTK6 in tumours is linked
      with the expression of HER2. METHOD AND RESULTS: In this study, we used the
      proximity ligation assay (PLA) technique on formalin-fixed paraffin sections from
      eighty invasive breast carcinoma tissue specimens to locate PTK6-HER2 protein
      protein complexes. Proximity ligation assay signals from protein complexes were
      assessed quantitatively, and expression levels showed a statistically significant
      association with tumour size (P=0.015) and course of the cancer disease
      (P=0.012). CONCLUSION: Protein tyrosine kinase 6 forms protein complexes with
      HER2 in primary breast cancer tissues, which can be visualised by use of the PLA
      technique. Human epidermal growth factor receptor 2-PTK6 complexes are of
      prognostic relevance.

PMID- 20700127
TI  - Similarities and differences in arterial responses to hypercapnia and visual
      stimulation.
AB  - Despite the different origins of cerebrovascular activity induced by neurogenic
      and nonneurogenic conditions, a standard assumption in functional studies is that
      the consequence on the vascular system will be mechanically similar. Using a
      recently developed arterial spin labeling method, we examined arterial blood
      volume, arterial-microvascular transit time, and cerebral blood flow (CBF) in the
      gray matter and in areas with large arterial vessels under hypercapnia, visual
      stimulation, and a combination of the two. Spatial heterogeneity in arterial
      reactivity was observed between conditions. During hypercapnia, large arterial
      volume changes contributed to CBF increase and further downstream, there were
      reductions in the gray matter transit time. These changes were not significant
      during visual stimulation, and during the combined condition they were moderated.
      These findings suggest distinct vascular mechanisms for large and small arterial
      segments that may be condition specific. However, the power relationships between
      gray matter arterial blood volume and CBF in hypercapnia (alpha=0.69+/-0.24) and
      visual stimulation (alpha=0.68+/-0.20) were similar. Assuming consistent
      capillary and venous volume responses across these conditions, these results
      offer support for a consistent total CBV-flow relationship typically assumed in
      blood oxygen-level dependent calibration techniques.

PMID- 20700128
TI  - Tumor necrosis factor alpha primes cerebral endothelial cells for erythropoietin
      induced angiogenesis.
AB  - Erythropoietin (EPO) enhances angiogenesis in the ischemic brain. Stroke induces
      secretion of tumor necrosis factor alpha (TNF-alpha). We investigated the effect
      of TNF-alpha on EPO-induced in vitro angiogenesis in cerebral endothelial cells.
      Using a capillary-like tubular formation assay, we found that transient
      incubation of primary rat cerebral microvascular endothelial cells (RECs) with
      TNF-alpha substantially upregulated EPO receptor (EPOR) expression and addition
      of EPO into TNF-alpha-treated RECs significantly augmented the capillary-like
      tube formation. Blockage of TNF receptor 1 (TNFR1) suppressed TNF-alpha
      upregulated EPOR expression and abolished EPO-induced tube formation. Attenuation
      of endogenous EPOR with small interfering RNA (siRNA) also inhibited EPO-enhanced
      tube formation. Treatment of RECs with EPO activated nuclear factor-kappa B (NF
      kappaB) and Akt. Incubation of the TNF-alpha-treated endothelial cells with EPO
      activated vascular endothelial growth factor (VEGF), VEGF receptor 2 (VEGFR2),
      angiopoietin 1 (Ang1), and Tie2. Blockage of VEGFR2 and Tie2 resulted in
      reduction of EPO-augmented tube formation. These data indicate that interaction
      of TNF-alpha with TNFR1 sensitizes cerebral endothelial cells for EPO-induced
      angiogenesis by upregulation of EPOR, which amplifies the effect of EPO on
      activation of the VEGF/VEGFR2 and Ang1/Tie2 pathways. Our results provide the
      evidence for crosslink between TNF and EPOR to coordinate the onset of
      angiogenesis in cerebral endothelial cells.

PMID- 20700129
TI  - HMBG1 mediates ischemia-reperfusion injury by TRIF-adaptor independent Toll-like
      receptor 4 signaling.
AB  - High-mobility group protein box-1 (HMGB1) has recently been recognized as a novel
      candidate in a specific upstream pathway promoting inflammation after brain
      ischemia. However, its downstream pathway and underlying mechanism have yet to be
      elucidated. The HMGB1 level in the acute cerebral infarct (ACI) group was
      significantly increased compared with that of control group, and correlated with
      the severity of neurologic impairment of ACI patients. Further, recombinant human
      HMGB1 (rhHMGB1) had no effect on microglia derived from mice lacking the Toll
      like receptor 4 (TLR4(-/-)). Intracerebroventricular injection of rhHMGB1 in
      TLR4(+/+) mice cause significantly more injury after cerebral ischemia
      reperfusion than control group. But, TLR4(-/-) mice administered with rhHMGB1
      showed moderate impairment after ischemia-reperfusion than TLR4(+/+) mice. To
      determine the potential downstream signaling of HMGB1/TLR4 in cerebral ischemic
      injury, we used the ischemic-reperfusion model with Toll/interleukin-1 receptor
      domain-containing adaptor-inducing interferon-beta knockout mice (TRIF(-/-)) and
      evaluated the activity and expression of TRIF pathway-related kinases. The
      results suggest that the TRIF pathway is not likely to be involved in TLR4
      mediated ischemia brain injury. Finally, we found that TLR4 expressed by
      immigrant macrophages was involved in the development of ischemic brain damage.
      These results suggest that HMBG1 mediates ischemia-reperfusion injury by TRIF
      adaptor independent Toll-like receptor 4 signaling. The TLR4 expressed by
      immigrant macrophages may be involved in the development of ischemic brain
      damage.

PMID- 20700130
TI  - alpha-MSH: a potential neuroprotective and immunomodulatory agent for the
      treatment of stroke.
AB  - Alpha-melanocyte-stimulating hormone (MSH) is a neuropeptide with profound
      immunomodulatory properties; we evaluated the effects of alpha-MSH on stroke
      outcome and its ability to modulate the postischemic immune response. In Lewis
      rats subjected to 3 hours of middle cerebral artery occlusion (MCAO), plasma
      concentrations of alpha-MSH rapidly decreased and returned to baseline over the
      course of days. Exogenous administration of alpha-MSH (100 or 500 MUg/kg)
      improved 24 hour outcome in animals subjected to 2 hours MCAO; alpha-MSH 500
      MUg/kg also decreased infarct volume at this time point. Both doses of alpha-MSH
      were ineffective in improving outcome or decreasing infarct volume in animals
      subjected to 3 hours MCAO. The splenocyte response to phytohemagglutin in animals
      treated with alpha-MSH was attenuated at 24 hours after MCAO. At 1 month after
      MCAO, treatment with alpha-MSH 500 MUg/kg at the time of stoke was associated
      with a decrease in TH1 response to myelin basic protein (MBP) in animals
      subjected to 2 hours MCAO, although treatment was not associated with improved
      outcome at this time point. Given the early benefits of alpha-MSH treatment and
      its effect on immunologic outcome, further studies to evaluate the utility of
      alpha-MSH for the treatment of cerebral ischemia are warranted.

PMID- 20700131
TI  - Comment on recent modeling studies of astrocyte-neuron metabolic interactions.
AB  - Recent years have seen a surge in mathematical modeling of the various aspects of
      neuron-astrocyte interactions, and the field of brain energy metabolism is no
      exception in that regard. Despite the advent of biophysical models in the field,
      the long-lasting debate on the role of lactate in brain energy metabolism is
      still unresolved. Quite the contrary, it has been ported to the world of
      differential equations. Here, we summarize the present state of this discussion
      from the modeler's point of view and bring some crucial points to the attention
      of the non-mathematically proficient reader.

PMID- 20700132
TI  - Distinct spatiotemporal patterns of spreading depolarizations during early
      infarct evolution: evidence from real-time imaging.
AB  - Experimental and clinical studies indicate that waves of cortical spreading
      depolarization (CSD) appearing in the ischemic penumbra contribute to secondary
      lesion growth. We used an embolic stroke model that enabled us to investigate
      inverse coupling of blood flow by laser speckle imaging (CBF(LSF)) to CSD as a
      contributing factor to lesion growth already in the early phase after arterial
      occlusion. Embolization by macrospheres injected into the left carotid artery of
      anesthetized rats reduced CBF(LSF) in the territories of the middle cerebral
      artery (MCA) (8/14 animals), the posterior cerebral artery (PCA) (2/14) or in
      less clearly defined regions (4/14). Analysis of MCA occlusions (MCAOs) revealed
      a first CSD wave starting off during ischemic decline at the emerging core
      region, propagating concentrically over large portions of left cortex. Subsequent
      recurrent waves of CSD did not propagate concentrically but preferentially
      circled around the ischemic core. In the vicinity of the core region, CSDs were
      coupled to waves of predominantly vasoconstrictive CBF(LSF) responses, resulting
      in further decline of CBF in the entire inner penumbra and in expansion of the
      ischemic core. We conclude that CSDs and corresponding CBF responses follow a
      defined spatiotemporal order, and contribute to early evolution of ischemic
      territories.

PMID- 20700134
TI  - Reversible dysfunction of receptors in traumatic brain injury?
AB  - In many brain disorders reduced binding of central benzodiazepine receptor
      ligands indicates irreversible neuronal damage. The data presented by Koizumi et
      al (2010) demonstrate that this is not the case in traumatic brain injury
      suggesting different pathogenetic mechanisms leading to tissue damage. The proof
      for this hypothesis requires further studies that should also consider thresholds
      of ligand binding as indicators of irreversible damage.

PMID- 20700133
TI  - Protein kinase C activation modulates reversible increase in cortical blood-brain
      barrier permeability and tight junction protein expression during hypoxia and
      posthypoxic reoxygenation.
AB  - Hypoxia (Hx) is a component of many disease states including stroke. Ischemic
      stroke occurs when there is a restriction of cerebral blood flow and oxygen to
      part of the brain. During the ischemic, and subsequent reperfusion phase of
      stroke, blood-brain barrier (BBB) integrity is lost with tight junction (TJ)
      protein disruption. However, the mechanisms of Hx and reoxygenation (HR)-induced
      loss of BBB integrity are not fully understood. We examined the role of protein
      kinase C (PKC) isozymes in modifying TJ protein expression in a rat model of
      global Hx. The Hx (6% O(2)) induced increased hippocampal and cortical vascular
      permeability to 4 and 10 kDa dextran fluorescein isothiocyanate (FITC) and
      endogenous rat-IgG. Cortical microvessels revealed morphologic changes in nPKC
      theta distribution, increased nPKC-theta and aPKC-zeta protein expression, and
      activation by phosphorylation of nPKC-theta (Thr538) and aPKC-zeta (Thr410)
      residues after Hx treatment. Claudin-5, occludin, and ZO-1 showed disrupted
      organization at endothelial cell margins, whereas Western blot analysis showed
      increased TJ protein expression after Hx. The PKC inhibition with chelerythrine
      chloride (5 mg/kg intraperitoneally) attenuated Hx-induced hippocampal vascular
      permeability and claudin-5, PKC (theta and zeta) expression, and phosphorylation.
      This study supports the hypothesis that nPKC-theta and aPKC-zeta signaling
      mediates TJ protein disruption resulting in increased BBB permeability.

PMID- 20700135
TI  - Vitamin D status and measures of cognitive function in healthy older European
      adults.
AB  - BACKGROUND/OBJECTIVES: Data from human studies that have investigated the
      association between vitamin D status and cognitive function in elderly adults are
      conflicting. The objective of this study was to assess vitamin D status
      (reflected by serum 25-hydroxyvitamin D (25(OH)D)) in older European subjects
      (n=387; aged 55-87 years) and examine its association with measures of cognitive
      function. SUBJECTS/METHODS: Serum 25(OH)D was assessed using enzyme-linked
      immunosorbent assay, whereas measures of cognitive function were assessed using a
      comprehensive Cambridge Neuropsychological Testing Automated Battery (CANTAB).
      RESULTS: In all, 12, 36 and 64% of subjects had serum 25(OH)D concentrations <30,
      <50 and <80 nmol/l, respectively, throughout the year. Serum 25(OH)D was
      significantly and inversely correlated with four assessments within the spatial
      working memory (SWM) test parameter (SWM between errors (r=-0.166; P=0.003); SWM
      between errors 8 boxes (r=-0.134; P=0.038); SWM strategy (r=-0.246; P<0.0001);
      and SWM total errors (r=-0.174; P<0.003)). When subjects were stratified on the
      basis of tertiles (T) of serum 25(OH)D (<47.6 (T(1)); 47.6-85.8 (T(2)); and >85.8
      (T(3)) nmol/l), fewer errors in SWM test scores occurred in subjects in the third
      T when compared with the first T (P<0.05-0.084). Stratification by sex showed
      that these differences between tertiles strengthened (P<0.001-0.043) in the
      females, but the differences were not significant (P>0.6) in males. CONCLUSIONS:
      Vitamin D insufficiency, but not deficiency, is widespread in the older
      population of several European countries. Low vitamin D status was associated
      with a reduced capacity for SWM, particularly in women.

PMID- 20700136
TI  - Associations between food patterns, socioeconomic position and working situation
      among adult, working women and men in Oslo.
AB  - BACKGROUND/OBJECTIVES: Socioeconomic disparities in diet are well documented, but
      the relative importance of different indicators of socioeconomic position (SEP)
      is not well known. The aim of this study was to explore relationships between
      food patterns, SEP (occupation, education and income) and degree of work control.
      SUBJECTS/METHODS: A cross-sectional population-based study 2000-2001, using three
      self-administered questionnaires including food frequency questions (FFQs).
      Factor analysis was used to explore food patterns. Participants include 9762
      working Oslo citizens, 30-60 years of age, having answered the questionnaires
      with <20% of the FFQ missing. RESULTS: Four food patterns were found: Western,
      prudent, traditional and sweet. In multivariate analyses, the likelihood of
      having a high intake of the Western pattern was lowest in the two highest
      educational groups (women: odds ratio (OR)=0.54/OR=0.75; men: OR=0.51/OR=0.76),
      and in the two highest occupational groups for men (OR=0.73/OR=0.78). The odds of
      having a high intake of the prudent pattern was highest in the two highest
      educational groups (women: OR=2.50/OR=1.84; men: OR=2.23/OR=1.37), and among the
      self-employed (women OR=1.61, men OR=1.68), as well as in the highest
      occupational group for men (OR=1.33). Women always having work control were least
      likely to have high intake of the Western pattern (OR=0.78) and most likely to
      have high intake of the prudent pattern (OR=1.39). CONCLUSIONS: The SEP
      indicators were in different ways related to the food patterns, but the effect of
      occupation and income was partly explained by education, especially among women.
      Women's work control and men's occupation were important for their eating habits.

PMID- 20700137
TI  - Nutrition assessment: the reproducibility of subjective global assessment in
      patients requiring mechanical ventilation.
AB  - BACKGROUND/OBJECTIVES: The detection of malnutrition in the intensive care unit
      (ICU) is critical to appropriately address its contribution on outcomes. The
      primary objective of this investigation was to determine if nutritional status
      could be reliably classified using subjective global assessment (SGA) in
      mechanically ventilated (MV) patients. SUBJECTS/METHODS: Fifty-seven patients
      requiring MV >48 h in a university-affiliated medical ICU were evaluated in this
      cross-sectional study over a 3-month period. Nutritional status was categorized
      independently by two registered dietitians using SGA. Frequencies, means (+
      s.d.), chi (2) and t-tests were used to describe the population characteristics;
      agreement between raters was evaluated using the kappa statistic. RESULTS: On
      admission, the average patient was 50.4 (+/-14.2) years of age, overweight (body
      mass index: 29.0+/-9.2kg/m(2)), had an acute physiology and chronic health
      evaluation II score of 24 (+/-10) and respiratory failure. Fifty percent (n=29)
      of patients were categorized as malnourished. Agreement between raters was 95%
      before consensus, reflecting near perfect agreement (kappa=0.90) and excellent
      reliability. Patients categorized as malnourished were more often admitted to the
      hospital floor before the ICU (n=32; 56%), reported decreased dietary intake (69
      vs 46%, P=0.02) and exhibited signs of muscle wasting (45 vs 7%, P<0.001,
      respectively) and fat loss (52 vs 7%, P<0.001, respectively) on physical exam
      when compared with normally nourished individuals. CONCLUSIONS: SGA can serve as
      a reliable nutrition assessment technique for detecting malnutrition in patients
      requiring MV. Its routine use should be incorporated into future studies and
      clinical practice.

PMID- 20700138
TI  - Trichuriasis and low-iron status in schoolchildren from Northwest Mexico.
AB  - BACKGROUND/OBJECTIVES: The aim of this study was to investigate the association
      between trichuriasis and iron status in rural schoolchildren from Northwest
      Mexico. SUBJECTS/METHODS: A total of 73 schoolchildren (37 boys, 36 girls)
      between the ages of 6 and 10 years were voluntarily recruited from the public
      primary school of the rural community of El Higueral in Culiacan, Sinaloa
      (Northwest Mexico) for a cross-sectional study with a longitudinal follow-up of 5
      weeks. Data were collected on socioeconomic status, anthropometry, haematological
      and biochemical indices of iron status, daily iron intake, and prevalence and
      intensity of trichuriasis. Multiple regression models, independent t-test and
      paired t-test were used to analyse the association between trichuriasis and iron
      status in cross-sectional and longitudinal samples, respectively. Adjusted models
      were tested for linear regression assumptions using residual plots. RESULTS: The
      mean age of the Trichuris-free and Trichuris-infected groups was 7.7+/-1.3 and
      7.7+/-1.5 years respectively (P=0.92). The height for age was significantly
      higher in the Trichuris-free group than the Trichuris-infected group (P=0.02). No
      differences were found in the socioeconomic variables between the two groups. At
      baseline, significantly higher concentrations of haemoglobin, haematocrit, blood
      cell count (RBC) and serum iron were measured in the Trichuris-free group
      compared with the Trichuris-infected children (P<0.05). An association was found
      between trichuriasis and haemoglobin adjusted for socioeconomic variables, age
      and sex. Haemoglobin, RBC and serum ferritin concentrations were significantly
      increased in the infected children 5 weeks after treatment (P<0.05). CONCLUSIONS:
      Trichuriasis could be a risk factor for low-iron status in the schoolchildren of
      Northwest Mexico.

PMID- 20700139
TI  - Genetic basis of sexual dimorphism in the threespine stickleback Gasterosteus
      aculeatus.
AB  - Sexual dimorphism (SD) in morphological, behavioural and physiological features
      is common, but the genetics of SD in the wild has seldom been studied in detail.
      We investigated the genetic basis of SD in morphological traits of threespine
      stickleback (Gasterosteus aculeatus) by conducting a large breeding experiment
      with fish from an ancestral marine population that acts as a source of
      morphological variation. We also examined the patterns of SD in a set of 38 wild
      populations from different habitats to investigate the relationship between the
      genetic architecture of SD of the marine ancestral population in relation to
      variation within and among natural populations. The results show that genetic
      architecture in terms of heritabilities, additive genetic variances and
      covariances (as well as correlations) is very similar in the two sexes in spite
      of the fact that many of the traits express significant SD. Furthermore,
      population differences in threespine stickleback body shape and armour SD appear
      to have evolved despite constraints imposed by genetic architecture. This implies
      that constraints for the evolution of SD imposed by strong genetic correlations
      are not as severe and absolute as commonly thought.

PMID- 20700140
TI  - Segregating variation for temperature-dependent sex determination in a lizard.
AB  - Temperature-dependent sex determination (TSD) was first reported in 1966 in an
      African lizard. It has since been shown that TSD occurs in some fish, several
      lizards, tuataras, numerous turtles and all crocodilians. Extreme temperatures
      can also cause sex reversal in several amphibians and lizards with genotypic sex
      determination. Research in TSD species indicates that estrogen signaling is
      important for ovary development and that orthologs of mammalian genes have a
      function in gonad differentiation. Nevertheless, the mechanism that actually
      transduces temperature into a biological signal for ovary versus testis
      development is not known in any species. Classical genetics could be used to
      identify the loci underlying TSD, but only if there is segregating variation for
      TSD. Here, we use the 'animal model' to analyze inheritance of sexual phenotype
      in a 13-generation pedigree of captive leopard geckos, Eublepharis macularius, a
      TSD reptile. We directly show genetic variance and genotype-by-temperature
      interactions for sex determination. Additive genetic variation was significant at
      a temperature that produces a female-biased sex ratio (30 degrees C), but not at
      a temperature that produces a male-biased sex ratio (32.5 degrees C). Conversely,
      dominance variance was significant at the male-biased temperature (32.5 degrees
      C), but not at the female-biased temperature (30 degrees C). Non-genetic maternal
      effects on sex determination were negligible in comparison with additive genetic
      variance, dominance variance and the primary effect of temperature. These data
      show for the first time that there is segregating variation for TSD in a reptile
      and consequently that a quantitative trait locus analysis would be practicable
      for identifying the genes underlying TSD.

PMID- 20700141
TI  - Superinfection of cytoplasmic incompatibility-inducing Wolbachia is not additive
      in Orius strigicollis (Hemiptera: Anthocoridae).
AB  - Cytoplasmic incompatibility (CI) allows the intracellular, maternally inherited
      bacterial symbiont Wolbachia to invade arthropod host populations by inducing
      infertility in crosses between infected males and uninfected females. The general
      pattern is consistent with a model of sperm modification, rescued only by egg
      cytoplasm infected with the same strain of symbiont. The predacious flower bug
      Orius strigicollis is superinfected with two strains of Wolbachia, wOus1 and
      wOus2. Typically, superinfections of CI Wolbachia are additive in their effects;
      superinfected males are incompatible with uninfected and singly infected females.
      In this study, we created an uninfected line, and lines singly infected with
      wOus1 and wOus2 by antibiotic treatment. Then, all possible crosses were
      conducted among the four lines. The results indicated that while wOus2 induces
      high levels of CI, wOus1 induces very weak or no CI, but can rescue CI caused by
      wOus2 to a limited extent. Levels of incompatibility in crosses with
      superinfected males did not show the expected pattern. In particular,
      superinfected males caused extremely weak CI when mated with either singly
      infected or uninfected females. An analysis of symbiont densities showed that
      wOus1 densities were significantly higher than wOus2 densities in superinfected
      males, and wOus2 densities were lower, but not significantly, in superinfected
      relative to singly infected males. These data lend qualified support for the
      hypothesis that wOus1 interferes with the ability of wOus2 to cause CI by
      suppressing wOus2 densities. To our knowledge, this is the first clear case of
      non-additive CI in a natural superinfection.

PMID- 20700143
TI  - DNA repair: a new fan of the Fanconi anaemia pathway.

PMID- 20700142
TI  - Central mechanisms of odour object perception.
AB  - The stimulus complexity of naturally occurring odours presents unique challenges
      for central nervous systems that are aiming to internalize the external olfactory
      landscape. One mechanism by which the brain encodes perceptual representations of
      behaviourally relevant smells is through the synthesis of different olfactory
      inputs into a unified perceptual experience--an odour object. Recent evidence
      indicates that the identification, categorization and discrimination of olfactory
      stimuli rely on the formation and modulation of odour objects in the piriform
      cortex. Convergent findings from human and rodent models suggest that distributed
      piriform ensemble patterns of olfactory qualities and categories are crucial for
      maintaining the perceptual constancy of ecologically inconstant stimuli.

PMID- 20700144
TI  - New functions of aminoacyl-tRNA synthetases beyond translation.
AB  - Over the course of evolution, eukaryotic aminoacyl-tRNA synthetases (aaRSs)
      progressively incorporated domains and motifs that have no essential connection
      to aminoacylation reactions. Their accretive addition to virtually all aaRSs
      correlates with the progressive evolution and complexity of eukaryotes. Based on
      recent experimental findings focused on a few of these additions and analysis of
      the aaRS proteome, we propose that they are markers for aaRS-associated functions
      beyond translation.

PMID- 20700145
TI  - Genetic marker polymorphisms on chromosome 8q24 and prostate cancer in the Dutch
      population: DG8S737 may not be the causative variant.
AB  - Prostate cancer is the most commonly diagnosed cancer in men in Europe and
      Northern America. Genome-wide association studies (GWAS) have detected an
      association with markers on chromosome 8q24. Allele -8 of microsatellite DG8S737
      with 22 repeats and allele A of the single-nucleotide polymorphism (SNP)
      rs1447295 have been found to be significantly associated with prostate cancer. As
      GWAS are subjected to type 1 error, confirmation studies are required to validate
      the results. Here, we analysed the same markers in 277 cases and 282 controls
      from the Netherlands using a nested case-control study. Incident prostate cancer
      cases and controls selected were identified in the population of the Netherlands
      Cohort Study. We also investigated clinical features of the disease by
      stratifying by tumour stage. We did not replicate the association with the SNP
      rs1447295-A allele (P=0.10), although the effect estimate was in the same
      direction as previous studies (odds ratio (OR), 1.38). Interestingly a
      statistically significant decreased risk was observed for DG8S737 allele -8 (OR,
      0.62; P=0.03). The apparent protective effect of the DG8S737 -8 allele observed
      in this study contrasts with the Amundadottir study. This suggests that DG8S737
      and rs1447295 might be tightly linked markers flanking the actual causative
      variant and that there may be potentially more than one high-risk haplotype
      present in the Caucasian population. This short report highlights the importance
      of validation, although further confirmation is still needed.

PMID- 20700146
TI  - Genetic diversity on the Comoros Islands shows early seafaring as major
      determinant of human biocultural evolution in the Western Indian Ocean.
AB  - The Comoros Islands are situated off the coast of East Africa, at the northern
      entrance of the channel of Mozambique. Contemporary Comoros society displays
      linguistic, cultural and religious features that are indicators of interactions
      between African, Middle Eastern and Southeast Asian (SEA) populations. Influences
      came from the north, brought by the Arab and Persian traders whose maritime
      routes extended to Madagascar by 700-900 AD. Influences also came from the Far
      East, with the long-distance colonisation by Austronesian seafarers that reached
      Madagascar 1500 years ago. Indeed, strong genetic evidence for a SEA, but not a
      Middle Eastern, contribution has been found on Madagascar, but no genetic trace
      of either migration has been shown to exist in mainland Africa. Studying genetic
      diversity on the Comoros Islands could therefore provide new insights into human
      movement in the Indian Ocean. Here, we describe Y chromosomal and mitochondrial
      genetic variation in 577 Comorian islanders. We have defined 28 Y chromosomal and
      9 mitochondrial lineages. We show the Comoros population to be a genetic mosaic,
      the result of tripartite gene flow from Africa, the Middle East and Southeast
      Asia. A distinctive profile of African haplogroups, shared with Madagascar, may
      be characteristic of coastal sub-Saharan East Africa. Finally, the absence of any
      maternal contribution from Western Eurasia strongly implicates male-dominated
      trade and religion as the drivers of gene flow from the North. The Comoros
      provides a first view of the genetic makeup of coastal East Africa.

PMID- 20700147
TI  - Nicotinic alpha5 receptor subunit mRNA expression is associated with distant 5'
      upstream polymorphisms.
AB  - CHRNA5, encoding the nicotinic alpha5 subunit, is implicated in multiple
      disorders, including nicotine addiction and lung cancer. Previous studies
      demonstrate significant associations between promoter polymorphisms and CHRNA5
      mRNA expression, but the responsible sequence variants remain uncertain. To
      search for cis-regulatory variants, we measured allele-specific mRNA expression
      of CHRNA5 in human prefrontal cortex autopsy tissues and scanned the CHRNA5 locus
      for regulatory variants. A cluster of six frequent single-nucleotide
      polymorphisms (rs1979905, rs1979906, rs1979907, rs880395, rs905740, and
      rs7164030), in complete linkage disequilibrium (LD), fully account for a >2.5
      fold allelic expression difference and a fourfold increase in overall CHRNA5 mRNA
      expression. This proposed enhancer region resides more than 13 kilobases upstream
      of the CHRNA5 transcription start site. The same upstream variants failed to
      affect CHRNA5 mRNA expression in peripheral blood lymphocytes, indicating tissue
      specific gene regulation. Other promoter polymorphisms were also correlated with
      overall CHRNA5 mRNA expression in the brain, but were inconsistent with allelic
      mRNA expression ratios, a robust and proximate measure of cis-regulatory
      variants. The enhancer region and the nonsynonymous polymorphism rs16969968
      generate three main haplotypes that alter the risk of developing nicotine
      dependence. Ethnic differences in LD across the CHRNA5 locus require
      consideration of upstream enhancer variants when testing clinical associations.

PMID- 20700148
TI  - Next generation sequencing in a family with autosomal recessive Kahrizi syndrome
      (OMIM 612713) reveals a homozygous frameshift mutation in SRD5A3.
AB  - As part of a large-scale, systematic effort to unravel the molecular causes of
      autosomal recessive mental retardation, we have previously described a novel
      syndrome consisting of mental retardation, coloboma, cataract and kyphosis
      (Kahrizi syndrome, OMIM 612713) and mapped the underlying gene to a 10.4-Mb
      interval near the centromere on chromosome 4. By combining array-based exon
      enrichment and next generation sequencing, we have now identified a homozygous
      frameshift mutation (c.203dupC; p.Phe69LeufsX2) in the gene for steroid 5alpha
      reductase type 3 (SRD5A3) as the disease-causing change in this interval. Recent
      evidence indicates that this enzyme is required for the conversion of polyprenol
      to dolichol, a step that is essential for N-linked protein glycosylation.
      Independently, another group has recently observed SRD5A3 mutations in several
      families with a type 1 congenital disorder of glycosylation (CDG type Ix, OMIM
      212067), mental retardation, cerebellar ataxia and eye disorders. Our results
      show that Kahrizi syndrome and this CDG Ix subtype are allelic disorders, and
      they illustrate the potential of next-generation sequencing strategies for the
      elucidation of single gene defects.

PMID- 20700150
TI  - Nasa patter.

PMID- 20700149
TI  - Patents.
AB  - 4,829,529; 4,853,940; 4,859,016; 4,896,324; 4,862,469; 4,888,776; 4,900,150;
      4,870,653; 4,881,237; 4,871,253; 4,907,235; 4,905,247; 4,907,237; 4,922,495;
      4,930,136; 4,942,582; 4,932,030; 4,949,347; 4,958,908; 4,968,887; 4,961,202;
      4,961,618; 4,973,119; 4,973,125; 4,974,923; 4,973,120; 4,974,228;

PMID- 20700152
TI  - Simple method of measuring the duration of short laser pulses.
AB  - We present a simple method to determine the duration of short laser pulses by
      measuring the efficiency of a second harmonic generation experiment.

PMID- 20700153
TI  - Method for calibrating heterodyne receiver arrays.
AB  - Modification of the transmitter section of a heterodyne laser radar to include
      two additional output beams at appropriate offset frequencies makes calibration
      of the local oscillator phases of a multichannel receiver possible.

PMID- 20700154
TI  - Stable operation of a powerful 3-Hz line tunable TEA CO(2) oscillator-amplifiers
      system.
AB  - We communicate results of the stable operation of a TEA CO(2) oscillator
      amplifiers system, producing pulses of 10(14) W/cm(2) at best focus, furnished
      with a simple provision for retropulse isolation.

PMID- 20700155
TI  - Generation of phase conjugate waves in dichromated gelatin and related materials.
AB  - Evidence is reported, we believe for the first time, on the generation of phase
      conjugate waves in dichromated gelatin, methylene blue doped gelatin, and
      methylene blue doped dichromated gelatin.

PMID- 20700156
TI  - Absorption behavior of neutral uranium atoms in a pulsed hollow cathode
      discharge.
AB  - The temporal behavior of uranium neutrals in the postdischarge conditions in a
      pulsed hollow cathode discharge has been investigated by monitoring the time
      dependent absorption of the output radiation of a single-axial-mode dye laser by
      uranium atoms. Studies of the kinetics of the absorption suggest that electron
      ion recombination followed by deactivation, Penning ionization, and diffusion to
      the cathode wall are the dominant mechanisms in the postdischarge conditions.

PMID- 20700157
TI  - Transverse modes of an apertured laser.
AB  - Modes of a diaphragmed laser are expressed as linear combinations of Laguerre
      Gauss functions and computed from the resonance condition. Hard and soft
      apertures are considered. Explicit results are given in both cases for the phase
      and amplitude distributions inside and outside a plano-concave cavity and for the
      three modes having the lowest losses. Deformations of modes with the diameter of
      the diaphragm are also given, showing the evolution of lateral lobes.

PMID- 20700158
TI  - Diode pumping of a solid state laser using evanescent field fiber optic coupling:
      a proposed technique.
AB  - The use of optical fibers to evanescently couple pump energy from laser diodes to
      a solid state laser rod is proposed. This technique involves placing a series of
      optical fibers side-by-side around the barrel portion of a laser rod, parallel to
      the laser resonator mode. A large index difference between the core region of the
      optical fibers and the solid state material facilitates evanescent coupling of
      pump light into the laser rod. Efficient operation will be possible due to a high
      overlap between the laser resonating mode and the pumped volume.

PMID- 20700159
TI  - Versatile integrated tunable diode laser system for high precision: application
      for ambient measurements of OCS.
AB  - A versatile and integrated tunable diode laser system for high precision
      measurements of the important sulfur gas carbonyl sulfide is described. We
      explicitly address some of the-major factors affecting tunable diode laser
      measurement precision as well as accuracy and have implemented a number of new
      features for increased system control and versatility. The system described
      herein provides the capability for measuring ambient concentrations of this gas
      with a precision in the range from +/-0.3 to +/-1% over time periods of many
      hours. Such a precision provides us with an important new capability for
      measuring true spatial and temporal variations of carbonyl sulfide in the
      atmosphere.

PMID- 20700160
TI  - Fluorescence in rare earth-doped fluorozirconate fibers.
AB  - Spontaneous fluorescence bands of erbium-, holmium-, and thulium-doped
      fluorozirconate fibers are studied experimentally and theoretically. From
      experimental data and for each trivalent ion we identify the set of optical
      transitions that gives rise to the observed linear fluorescence and upconversion
      process. Fiber perturbation theory and density matrix formalism are used to model
      fluorescence spectra with particular attention to modal structure, loss, and mode
      coupling in the fiber. The relationship between the experimental emission
      spectrum of thulium-doped fiber and the theoretical model is discussed.

PMID- 20700161
TI  - Method for measuring transfer function and impulse response of a single-fiber
      interferometric sensor.
AB  - This paper describes a method for measuring the transfer function and impulse
      response of a single-fiber interferometric sensor. A change in phase retardation
      is extracted directly from a beat photocurrent generated by superimposing the
      orthogonally polarized optical waves of different frequency propagating along the
      slow and fast axes of the fiber. Axial vibrations with a known Gaussian spectrum
      given to the fiber enable us to measure the transfer function and impulse
      response in the linear frequency range of the overall sensing system.

PMID- 20700162
TI  - Correlation of single-mode fiber radiation response and fabrication parameters.
AB  - Statistically significant correlations have been established between certain
      fabrication parameters of matched clad, single-mode optical fiber waveguides and
      their response to an ionizing radiation dose of 2000 rad. The reCOVE:ry data
      measured at -35 degrees C following exposure have been fit to nth-order kinetic
      behavior where the adjustable parameters are the initial and permanent
      incremental losses (A(o) and A(f), respectively), the half-life of attenuation
      tau, and the order of kinetics n. The set of fibers chosen for analysis had Ge
      doped silica cores. In fibers with Ge-F-doped silica clads, A(o) correlates with
      the concentration of Ge-doped into the fiber core; A(f) correlates with the ratio
      of oxygen to reagents used during core deposition; and tau and n correlate with a
      two-way interaction of core oxygen and fiber draw speed. In P-F-doped clad
      fibers, the P concentration has been found to correlate with the order of the
      kinetics of recovery.

PMID- 20700163
TI  - Single-mode fiber microlens with controllable spot size.
AB  - A novel method for fabricating microlenses on tapered single-mode fibers is shown
      to be able to control the lens spot size. The fiber cladding is first
      symmetrically tapered by etching it with an evaporating ammonium bifluoride
      solution. A hemispheric lens is then melted on the taper tip with a CO(2) laser.
      The lens can reduce the fiber mode radius to 40% of its original value. A
      theoretical calculation of the focused spot size agrees well with experimental
      results.

PMID- 20700164
TI  - Three-dimensional (BiY)(3)Fe(5)O(12) waveguide with a load layer made of SiO(2).
AB  - We have developed a loaded (BiY)(3)Fe(5)O(12) waveguide for integrated
      magnetooptic devices. The load layer made of SiO(2) was fabricated with a
      reactive ion etching using CHF(3) gas. The waveguiding loss was measured by the
      streak method and by the cutback method. The measured values were <7 cm(-1), and
      the waveguiding loss caused by the lateral confinement was deduced to <1 cm(-1).

PMID- 20700165
TI  - Multiplex CARS for simultaneous measurement of temperature and CO(2) and H(2)
      concentrations in a combustion environment.
AB  - Simultaneous temperature and CO(2) concentration measurements with multiplex
      coherent anti-Stokes Raman scattering (CARS) spectra of CO(2) were performed.
      CARS spectra of pure CO(2) and various mixtures of CO(2) and N(2) in a furnace
      were recorded at various temperatures to test the computer code that simulates
      CO(2) CARS spectra using recent spectroscopic constants. The temperatures
      obtained from the CO(2) CARS spectra were in good agreement with thermocouple
      temperature measurements. However, the CO(2) concentrations cannot be accurately
      extracted from these spectra. It is believed by the authors that the cross
      coherent effect, which has not been included in the present model, and the
      difficulty of accurately accounting for the background are two important factors
      affecting the CO(2) concentration measurements. H(2) pure rotational lines S(4)
      and S(5) were found in the CO(2) CARS spectra of a hydrocarbon flame. These
      assignments were confirmed from intensity ratio measurements of S(4) and S(5)
      lines at different temperatures. A theoretical study shows that the H(2)
      concentration measurement from the S(5) line should be more sensitive than that
      of the S(4) and S(9) lines at the flame temperature. CARS spectra of preanalyzed
      mixtures of N(2), CO(2), and H(2) in a furnace were recorded to investigate the
      feasibility of inferring the H(2) concentration from these spectra. Simultaneous
      CO(2) and H(2) multiplex CARS spectra were also recorded in a CH(4)/O(2)
      diffusion flame and in the MSU/DIAL test stand to observe the high temperature
      spectra. The results of these measurements are presented.

PMID- 20700166
TI  - Optical fiber measurements of particle velocity using laser-induced
      phosphorescence.
AB  - An optical fiber anemometer that uses laser-induced phosphorescence to measure
      particle time of flight in dense gas-solid suspensions is described. The
      anemometer is tested using a spinning disk coated with a phosphor having a
      persistent afterglow. The diagnostic technique is illustrated by measuring the
      velocity of free-falling particles coated with the same phosphor. Monte Carlo
      simulations are employed to determine the optical characteristics of the probe,
      including its measurement volume.

PMID- 20700167
TI  - Aperture averaging of optical scintillations in the turbulent atmosphere.
AB  - We have developed approximate expressions for the aperture-averaging factor of
      optical scintillation in the turbulent atmosphere. For large apertures and weak
      path-integrated turbulence with a small inner scale, the variance of signal
      fluctuations is proportional to the -7/3 power of the ratio of the aperture
      diameter to the Fresnel zone size. If the inner scale is large, the variance is
      proportional to the -7/3 power of the ratio of the aperture diameter to the inner
      scale. In strong path-integrated turbulence, two scales develop. That portion of
      the variance associated with the smaller scale is proportional to the -2 power of
      the ratio of the aperture diameter to the phase coherence length. That portion of
      the variance associated with the larger scale is proportional to the -7/3 power
      of the ratio of the aperture diameter to the scattering disk. These simple
      approximations are within a factor of 2 of the measurements.

PMID- 20700168
TI  - Transmission window near 2400 cm(-1): an experimental and modeling study.
AB  - The absorption in the 2400-cm(-1) region is dominated by continuum absorptions
      from carbon dioxide and nitrogen, and it is important to be able to describe the
      temperature dependence of these two continua. A series of measurements of
      atmospheric transmission over a 5.7-km range were carried out during the summer
      and winter seasons of 1988. Following a brief description of the experiments a
      selected number of spectra, covering the temperature range from -21.4 to 30.3
      degrees C, are presented. These measurements are compared with predictions by the
      atmospheric transmission model FASCOD2 and modified versions using models of the
      carbon dioxide and the nitrogen continua derived from experimental laboratory
      measurements. Finally, an improved temperature-dependent model for the nitrogen
      continuum is derived from atmospheric transmission measurements. The model covers
      the range of temperatures found in the troposphere and differs significantly from
      laboratory-based measurements.

PMID- 20700169
TI  - Mobile lidar for simultaneous measurements of ozone, aerosols, and temperature in
      the stratosphere.
AB  - A Meteorological Research Institute Mark II mobile lidar was developed for
      simultaneous measurements of ozone, temperature, and aerosols in the
      stratosphere. The lidar consists of an XeCl laser, a Nd:YAG laser, and an 80-cm
      diam receiving telescope. The laser beams at three wavelengths (308, 355, and 532
      nm) can be almost simultaneously transmitted. The purpose of this lidar is to
      study, for example, the aerosol impact on the ozone layer through radiative and
      photochemical processes, the aerosol impact on the Umkehr measurements after
      violent volcanic eruptions, and the interaction between temperature and ozone.
      The performance of the lidar system and some data about ozone, aerosols, and
      temperature are described.

PMID- 20700170
TI  - Coherent lidar airborne windshear sensor: performance evaluation.
AB  - National attention has focused on the critical problem of detecting and avoiding
      windshear since the crash on 2 Aug. 1985 of a Lockheed L-1011 at Dallas/Fort
      Worth International Airport. As part of the NASA/FAA National Integrated
      Windshear Program, we have defined a measurable windshear hazard index that can
      be remotely sensed from an aircraft, to give the pilot information about the wind
      conditions he will experience at some later time if he continues along the
      present flight path. A technology analysis and end-to-end performance simulation
      measuring signal-to-noise ratios and resulting wind velocity errors for competing
      coherent laser radar (lidar) systems have been carried out. The results show that
      a Ho:YAG lidar at a wavelength of 2.1 microm and a CO(2) lidar at 10.6 microm can
      give the pilot information about the line-of-sight component of a windshear
      threat from his present position to a region extending 2-4 km in front of the
      aircraft. This constitutes a warning time of 20-40 s, even in conditions of
      moderately heavy precipitation. Using these results, a Coherent Lidar Airborne
      Shear Sensor (CLASS) that uses a Q-switched CO(2) laser at 10.6 microm is being
      designed and developed for flight evaluation in the fall of 1991.

PMID- 20700171
TI  - Point spread function in ocean water: comparison between theory and experiment.
AB  - A new instrument to measure the point spread function (PSF) in the ocean has
      provided the opportunity for direct comparison between theoretical predictions
      and experimental measurement. Theoretical predictions are derived from small
      angle scattering theory using a simple algebraic fit to the single scattering
      phase function. The resulting predictions for the PSF are found to match the
      experimental measurements over a wide range of angles and optical depths.

PMID- 20700172
TI  - Monte Carlo study of light propagation in optically thick media: point source
      case.
AB  - The results of a Monte Carlo study on light propagation in dense turbid media are
      presented. The calculations refer to the radiation emerging from a spherical
      scattering cell containing the diffusing medium (no diffusers outside the cell
      are considered) in whose center a point source is placed. Both the total
      scattered power emerging from the sphere and the impulse response were evaluated
      for a large range of optical depths and different types of diffuser. The results
      pertaining to both the radiance at the surface of the scattering cell and the
      impulse response are described by simple empirical relations. The results suggest
      a method of measuring the albedo and the asymmetry factor of the diffusing
      medium. A comparison with some results of the diffusion approximation is also
      presented.

PMID- 20700173
TI  - Approximation to extinction efficiency for randomly oriented spheroids.
AB  - A semiempirical approximation to the extinction efficiency Q(ext) for randomly
      oriented spheroids, based on an extension of the anomalous diffraction formula,
      is given and compared to the extended boundary condition method or T-matrix
      method. Using this formula, Q(ext) can be evaluated over 10(4) times faster than
      by previous methods. This approximation has been verified for complex refractive
      indices m = n - ik, where 1.01 </= n >/= 2.00 and 0 </= k >/= 1 and aspect ratios
      from 0.5 to 4. We believe the approximation is uniformly valid over all size
      parameters and aspect ratios. It has the correct Rayleigh and large particle
      asymptotic behavior. The accuracy and limitations to this formula are extensively
      discussed.

PMID- 20700174
TI  - Patents.
AB  - 4,854,704; 4,870,648; 4,885,471; 4,887,900; 4,909,612; 4,925,307; 4,937,833;
      4,938,563; 4,948,228; 4,958,914; 4,973,122; 4,972,699;
      4,964,708;4,973,113;4,973,114; 4,973,115; 4,973,832; 4,977,560; 4,978,184;
      4,979,827; 4,979,788; 4,979,807; 4,979,820; 4,979,824; 4,978,185; 4,983,825.

PMID- 20700176
TI  - Computer-controlled two-color laser-based optical stimulator for vision research.
AB  - A two-color laser-based stimulator is described. This device produces high
      intensity uniform field illumination with temporal control over a wide range of
      temporal frequencies. In addition it can be used to produce wide field flicker
      (40 degrees ).

PMID- 20700177
TI  - Cryogenic radiometry: the problem of hydrogen condensation in detectors operated
      at temperatures below 4 K.
AB  - Cryogenic radiometers employing a detector at liquid helium temperatures have
      demonstrated a much improved accuracy over those operating at room temperature.
      It is recommended that detectors be operated at temperatures below 3 K.

PMID- 20700178
TI  - Reflectometer for absolute silicon radiometry.
AB  - A simple sphere-based reflectometer for the determination of the reflectance of
      silicon photodiodes at normal incidence is described.

PMID- 20700179
TI  - Is biomedical research a national priority?
AB  - Funding for independent biomedical research is little more than noise in the
      federal budget. As a result, the infrastructure of people who generate new
      information is being decimated. The nation's economic stability and long-term
      economic growth supported by this infrastructure are threatened. Researchers need
      to take positive action to reverse this trend by actively participating in the
      decision process at all levels.

PMID- 20700180
TI  - Non-invasive assessment of the visual system: introduction by the feature
      editors.
AB  - This is an introduction to the papers that compose the fourth feature issue on
      noninvasive assessment of the visual system and discusses issues related to
      publishing in Applied Optics.

PMID- 20700181
TI  - Near-IR retinal laser Doppler velocimetry and flowmetry: new delivery and
      detection techniques.
AB  - In laser Doppler velocimetry and flowmetry of the human ocular fundus, near
      infrared diode lasers, coupled with avalanche photodiode detectors, offer much
      improved signal-to-noise ratio compared to He-Ne laser delivery and
      photomultiplier tube detection. The increased signal-to-noise ratio is achieved
      through increased retinal irradiance and better quantum efficiency of the
      avalanche photodiode in the near infrared. Furthermore, the small size of the
      diode lasers allows delivery of two individually steerable beams for simultaneous
      measurements in different parts of the fundus. Applications are given as
      illustrations of the capabilities of the system: retinal laser Doppler
      velocimetry in humans without need for pupil dilatation and optic nerve head
      laser Doppler flowmetry in the cat using flicker as a stimulus to induce blood
      flow changes.

PMID- 20700182
TI  - Interferometric measurement of visual acuity and the effect of ocular chromatic
      aberration.
AB  - Ocular chromatic aberration is expected on theoretical grounds to affect the
      quality of polychromatic interference fringes generated on the retina if the
      interferometer is not perfectly centered on the eye's visual axis. Of primary
      concern is a loss of contrast resulting from wavelength-dependent phase shifts of
      the fringes. By using an interferometer with just two wavelengths of light, we
      demonstrated this phase shift directly and measured its magnitude as a function
      of interferometer displacement. Then, using white-light fringes we measured
      visual acuity and found a threefold loss of acuity when the light from the
      interferometer entered the eye near the margin of the pupil. These results are
      consistent with predictions based on a simple optical model of ocular chromatic
      aberration.

PMID- 20700183
TI  - Acquisition of the curves of the human crystalline lens from slit lamp images: an
      application of the Hough transform.
AB  - To accurately model lens-based functions such as accommodation and image
      formation on the retina, it is essential to know anterior chamber depth, anterior
      segment length, lens thickness, and, most importantly, lens curvature both on the
      surfaces and internally. With the exception of lens curvatures, all these data
      can be obtained with a high degree of precision by one or more techniques (i.e.,
      A-scan ultrasonography and pachymetry). Lens curvatures can be collected by
      Scheimpflug slit lamp photography, but the curvature data must be extracted from
      these images, a problem complicated by both linear and nonlinear image
      distortion. Previous approaches have involved significant magnification of the
      image combined with major subjective input and judgment. We present here a
      computer-based application of the Hough technique for measurement of curvature of
      lens surfaces observed in Scheimpflug slit lamp photography and related
      evaluation of (and solutions for) the associated image distortion. Minimal user
      input is required for successful application of this method, but the time
      required to obtain a fit for each surface is >1 min. Results obtained by this
      technique on test images compare favorably with those obtained by independent
      methods.

PMID- 20700184
TI  - Location of nonlinear processes within the pupillary pathway.
AB  - The pupil oscillates in synchrony with a slow beat produced by adding two lights
      flickering at slightly different frequencies. This behavior shows that nonlinear
      processes are present within the pathway. To localize these processes, a light of
      one frequency was presented to one eye, while a light of a different frequency
      was presented to the other. No pupil oscillations were seen in response to the
      beat in these dichoptic conditions, but when both lights were superimposed and
      presented to the same eye a powerful pupillary response was produced. We conclude
      that the nonlinearity giving rise to the pupil's beat response occurs before the
      pathways from the two eyes join and hence is neural rather than muscular in
      origin. Furthermore, the lack of a pupil response in the dichoptic conditions
      suggests that the signals from the two eyes may combine linearly.

PMID- 20700185
TI  - Automated estimation of implicit time and amplitude from the flicker
      electroretinogram.
AB  - The electroretinogram (ERG) has been shown to yield sensitive and specific
      information about the development of neovascularization in ischemic disorders
      such as diabetic retinopathy and central retinal vein occlusion. However, even
      though the test is quick, easy to perform, and carries few risks, the ERG is
      poorly utilized in clinical situations because of the extended training period
      necessary for test interpretation. We have developed an algorithm that estimates
      the phase and amplitude of a 30-Hz flicker ERG and that is relatively insensitive
      to many forms of interference in ERG recordings. These estimates can be directly
      compared to established criteria for the risk of proliferative retinal disease.

PMID- 20700186
TI  - Irregularities in the flicker sensitivity curve.
AB  - The flicker sensitivity of the human eye may be characterized by the De Lange
      curve (temporal modulation transfer function plot). In the curves of two out of
      eight observers, D. H. Kelly [J. Opt. Soc. Am. 52,940-947 (1962)] found three
      peaks instead of one, as had been reported in previous publications, and
      suggested that they are related to the three mechanisms of color vision. Several
      investigations have been based on this suggestion, but there has been no
      confirmation of his observation. In this paper, a new measuring method was
      devised and the existence of the peaks was confirmed, but the hypothesis that
      they are related to color processes was questioned.

PMID- 20700187
TI  - Profound reductions of flicker sensitivity in the elderly: can glaucoma involve
      the retina distal to ganglion cells?
AB  - Flicker sensitivities were measured for more than 100 people age 60 and older
      with stimulus-conditions originally designed to obtain estimates of preretinal
      absorption by the lens and macular pigment. Flicker sensitivities were measured
      on two chromatic backgrounds: a 1000-td, 480-nm background and a 5800-td, Wratten
      33 background (approximately metameric with 633 nm). Testing sessions were
      administered at 18-month intervals across a 3-yr period. No subject tested had a
      history of glaucoma or ocular hypertension at the time of entry into the study.
      For ten subjects, however, flicker sensitivity was sometimes reduced by more than
      2.0 log units from the mean norm for at least one of the two backgrounds. For
      most other subjects, flicker sensitivities were within 0.5 log units of the mean
      norms. On retrospective analysis, the profound reductions of flicker sensitivity
      (PRFS) were associated significantly with (a) advanced age (perhaps especially
      when combined with relatively high intraocular pressure), and (b) the use of
      cardiovascular medications. The PRFS probably were associated with (c) female
      sex, and (d) large intraocular pressure fluctuations. In addition, the majority
      of subjects with PRFS were found to have evidence of glaucomatous cupping or
      field loss. These results suggest that PRFS result from glaucoma or share
      etiologies with low-tension glaucoma. The use of cardiovascular medications
      suggested that PRFS could depend on retinal dysfunction rather than on optic
      nerve compromise alone. Predicted results from two additional subject populations
      support this possibility. For young healthy subjects, flicker threshold vs
      illuminance curves attained very steep slopes for sufficiently short wavelength
      tests on sufficiently extreme long wavelength backgrounds (655 nm, 50,000 td);
      the steep slopes coincided with the breakdown of effective M-cone isolation.
      Reductions of flicker sensitivity on the 5800-td Wratten 33 background depended
      correspondingly on test wavelength for subjects with well-documented low-tension
      glaucoma.

PMID- 20700188
TI  - Temporal and spatial response properties of optic neuritis patients manifesting
      statokinetic dissociation.
AB  - Statokinetic dissociation (SKD) refers to a greater reduction in sensitivity to
      stationary visual stimuli relative to similar targets in motion. We evaluated SKD
      perimetrically in nine optic neuritis (ON) patients and in nine normals by
      measuring the difference between static and 4 degrees /s kinetic thresholds for a
      size I target (0.11 degrees ) along the four oblique meridians. To assess
      temporal response characteristics, we used flicker perimetry to measure the
      sensitivity to 2-, 8-, and 20-Hz sinusoidal flicker at 5 degrees intervals along
      the oblique meridians. The ON patients' sensitivity to all three flicker
      frequencies was reduced at all eccentricities. In a number of cases, flicker
      sensitivity was unmeasurable to one or more frequencies within the region where
      kinetic targets were detectable. This was particularly marked at 20-25 degrees ,
      where in half the cases there was no measurable sensitivity to a flickering
      target although a moving target could be seen. These results indicate that SKD in
      these patients may not be due to a selective loss of mechanisms sensitive to low
      frequency temporal modulation with a relative sparing of mechanisms sensitive to
      high-frequency temporal modulation as has been previously suggested [A. Safran
      and J. Glaser, "Statokinetic Dissociation in Lesions of Anterior Visual
      Pathways," Arch. Ophthalmol. 98, 291-295 (1980)]. We hypothesize that SKD may be
      due in part to differences in spatial summation in these patients, making a
      moving target, which has a greater spatial extent, more detectable than a
      stationary target. Thus ON patients exhibiting SKD should show great improvement
      in static perimetry thresholds as the target size is increased. We compared the
      results of standard 30-2 Humphrey perimetry for size III (0.43 degrees ) and size
      V (1.72 degrees ) targets for normals and ON patients and found that the patients
      showed a larger sensitivity difference between size III and size V targets than
      normals.

PMID- 20700189
TI  - Confocal scanning optical microscope using single-mode fiber for signal
      detection.
AB  - A single-mode fiber is employed as a detector in a confocal scanning optical
      microscope (CSOM) instead of a pinhole and its optical property is studied. The
      optical system is always coherent, which is fundamentally different from the CSOM
      with a finite-sized pinhole. The coherent transfer function and the axial
      response are calculated. Experimentally, the coherent image is taken and the
      axial response is also measured.

PMID- 20700190
TI  - Design of diffractive singlets for monochromatic imaging.
AB  - The Seidel aberrations of a rotationally-symmetric diffractive lens with an
      arbitrary phase profile are presented. It is shown that by a proper choice of
      phase function and aperture stop position, third-order coma and astigmatism can
      be eliminated for any chosen conjugate ratio. Since a diffractive lens has an
      inherent zero value for the Petzval sum, the image plane is flat in both
      tangential and sagittal meridians. The substrate curvature of the lens may be
      chosen to introduce a prescribed amount of distortion to allow for use as a
      Fourier transform lens or a laser scan lens. Examples are given of lens
      performance in finite conjugate imaging and laser scanning, where the f - theta
      condition is satisfied.

PMID- 20700191
TI  - Ray tracing of optically modified fiber tips. 1: spherical probes.
AB  - The beam profiles and spatial irradiance distributions of modified fiber tips
      mainly used in laser angioplasty have been calculated by ray tracing assuming a
      uniform spatial combined with a weighted angular irradiance distribution. The
      computations were compared to paraxial theory and to measurements in air and in
      water. For ball-shaped fibers and hemispherical probes, made of either silica or
      sapphire, the position of the maximum irradiance in front of the probe in water
      did not coincide with the calculated paraxial focal point. The maximum irradiance
      increase was limited by internal backward reflections and by beam divergence. It
      is expected that beam focusing is minimal when optically modified fiber tips are
      in contact with tissue. Ray tracing is useful for optimizing the design of
      optically modified fiber tips when paraxial theory cannot be applied.

PMID- 20700192
TI  - Ray tracing of optically modified fiber tips. 2: laser scalpels.
AB  - The spatial irradiance distribution of tapered fibers and tapered rods used as
      scalpels in laser surgery has been calculated by ray tracing. The results were
      compared to measurements in air and in water. The beam profiles of laser scalpels
      were conically shaped at discrete angles related to the number of reflections
      within the scalpel. Light started to leak radially out of the scalpel before it
      reached the tip slightly suppressing the increase in fluence rate toward the tip.
      For effective tissue cutting, the scalpel tip may be shortened to optimize the
      irradiance increase in combination with radial energy leakage to obtain
      controlled hemostatic coagulation.

PMID- 20700193
TI  - Photometry of diode emitters: light emitting diodes and infrared emitting diodes.
AB  - New methods are described for luminous intensity and luminous flux determination
      for small light sources. Introduction of a special multiple point method and
      correction techniques for integrating spheres are shown.

PMID- 20700194
TI  - Light hazards to the patient's retina from ophthalmic instruments.
AB  - The spectral radiance and irradiance of several common ophthalmic instruments
      were measured. The respective spectral retinal irradiance a patient might receive
      was calculated. To evaluate the potential light hazard to the patient's retina,
      we calculated the temperature rise resulting from light absorption at the fundus,
      compared retinal irradiance with threshold values for photochemical retinal
      damage, and correlated them with safety guidelines. A thermal hazard to the
      patient's retina can result from operation microscopes if light output is maximal
      and exposure prolonged. Comparison of light exposures from different ophthalmic
      instruments with thresholds for photochemical-induced lesions showed that one has
      to be more concerned about the actinic effect of light exposure. At maximum lamp
      voltage, the light exposure from operation microscopes reaches thresholds for
      photochemical damage even after a few minutes. Other ophthalmic instruments
      present no particular hazard if they are used at common exposure durations.
      Application of laser safety guidelines confirm these results. In some cases,
      light from operation microscopes exceeds the safety margin in <1 min.

PMID- 20700195
TI  - Phase measurements using the Mirau correlation microscope.
AB  - A new algorithm for extracting amplitude and phase information from the data
      collected by the Mirau correlation microscope is presented. The accuracy of the
      phase measurements is first determined by measuring phase steps and vertical
      resolutions in the nanometer range. Experimental results with metal gratings show
      good agreement with Fourier theory. An inverse filter is then used to improve the
      resolution of the system. The filtered image has sharper edges and better phase
      contrast.

PMID- 20700196
TI  - Video microscope with submicrometer resolution.
AB  - We have constructed and evaluated a video microscope with a 150- x 150-microm
      field of view for performing measurements of optical fiber geometry. The
      microscope consists of a frame transfer video camera, condensing and filtering
      optics, a 40x, 0.65 N.A. microscope objective, and frame digitizing electronics.
      Using simple digital algorithms, we measure distance with a random uncertainty of
      approximately 40 nm across the full field of view, but width measurements suffer
      from a systematic error between 0.1 and 0.2 microm.

PMID- 20700197
TI  - Two-wavelength beam deflection technique for electron density measurements in
      laser-produced plasmas.
AB  - We describe the use of a two-wavelength beam deflection technique in the
      measurement of electron density and expansion velocity in a laser-produced
      plasma. Beam deflection measurements are made with a spatial resolution of 250
      microm, temporal resolution of 25 ns, and a dynamic range of 1000. Several
      techniques for determining the spatial and temporal variation of the electron
      density from beam deflection measurements are described.

PMID- 20700198
TI  - Eye-safe laser scanner for range imaging.
AB  - A fast, range imaging, eye-safe laser scanner which uses a synchronized scanning
      geometry is described. The device operates at a 1.5-microm wavelength and
      incorporates an Er doped fiber laser as well as an InGaAs position sensitive
      detector. Factors influencing device performances are presented along with range
      images obtained at 1.5 microm.

PMID- 20700199
TI  - Angular scattering from optical interference coatings: scalar scattering
      predictions and measurements.
AB  - A scalar scattering theory is developed that predicts the angular distribution of
      light scattered and the total integrated scatter from a randomly rough or
      inhomogeneous optical interference coating. Three types of random variation are
      considered: uncorrelated roughness, additive roughness, and uncorrelated index
      inhomogeneity. The scattering calculations are formulated so that the output of
      any conventional thin film analysis program along with a coating's surface or
      index statistics could be used to calculate the scattering distribution of a
      coating. The scattering calculations are compared to experimental measurements
      from a sixteen-layer high reflector coating with small additive roughness sigma =
      2.4 A and large correlated roughness sigma = 93 A.

PMID- 20700200
TI  - Extreme ultraviolet performance of a multilayer coated high density toroidal
      grating.
AB  - The performance of a multilayer coated diffraction grating has been evaluated at
      EUV wavelengths both in terms of absolute efficiency and spectral resolution. The
      application of a ten-layer Ir/Si multilayer coating to a 3600-lines/mm blazed
      toroidal replica grating produced a factor of 9 enhancement in peak efficiency
      near the design wavelength approximately 30 nm in first order, without degrading
      its excellent quasistigmatic spectral resolution. The measured EUV efficiency
      peaked at 3.3% and was improved over the full spectral range between 25 and 35 nm
      compared with the premultilayer replica which had a standard gold coating. In
      addition, the grating's spectral resolution of >5000 was maintained.

PMID- 20700201
TI  - Thermally induced interfacial stresses in a thin film on an infinite substrate.
AB  - The thermally induced stresses in a thin film deposited on an infinite substrate
      is approximated by means of the theory of elasticity and strain energy
      minimization. The results are applied to the growth of a thick layer of zinc
      selenide onto a film of polycrystalline diamond. The conclusion is that the
      thermally induced stresses alone will be much higher than normally encountered in
      coating work.

PMID- 20700202
TI  - Optical loss distribution in anodically oxidized alumina with a 2-D structure.
AB  - Optical losses have been measured for anodized alumina films with 100-200-A size
      microstructure. A significant loss increase is seen near the surface of the film,
      and such a loss distribution disappears by treating the film with hot water or
      glycerin. The optical loss also depends strongly on the direction of
      polarization. An alumina microstructure has been modeled based on electron
      microscope observations, and optical losses have been calculated theoretically.
      From a comparison of experimental and theoretical results, it would appear that
      distribution and anisotropy of optical losses are caused by conical micropores
      and aluminum microcolumns.

PMID- 20700203
TI  - Photorefraction of the living eye: a model for linear knife edge photoscreening.
AB  - A computer model is developed to explain colored artifacts in pupil images of the
      living human eye formed by the linear knife edge photoscreener. An approximate
      expression for the RGB irradiances recorded by the photoscreener is derived by
      using the statistical properties of the line spread functions that characterize
      the source, the aberrations of the eye, and the reflecting properties of the
      retina. The pupil image for each color is shown to be very much a map of the
      deviations perpendicular to the knife edge imposed on rays by an equivalent
      aberration plate, and the overall response of the photoscreener to specific
      aberrations of the eye is cataloged for errors of accommodation and chromatic
      aberration, spherical aberration, astigmatism, and tear bands.

PMID- 20700205
TI  - Applied optics of optics and optics.

PMID- 20700204
TI  - Patents.
AB  - 4,966,426, 4,966,440, 4,966,428, 4,973,132, 4,968,108, 4,969,700, 4,971,409,
      4,974,920, 4,984,856, 4,986,624, 4,976,504, 4,976,507.

PMID- 20700206
TI  - Time resolved imaging at 130 A with submicron resolution.
AB  - A novel and simple XUV imaging technique using a laser-produced plasma source is
      described. A spatial resolution of better than 0.8 mum is demonstrated.

PMID- 20700207
TI  - Optical digital processor using arrays of symmetric self-electrooptic effect
      devices.
AB  - Four arrays of thirty-two GaAs symmetric self-electrooptic effect devices were
      optically interconnected to form a looped-pipeline optical digital processor.
      Several circuits were demonstrated, including two shift registers and a decoder
      circuit. Clock frequencies of up to 1 MHz were attained. Possible extensions to
      and limitations of this system are described.

PMID- 20700208
TI  - Optical cellular logic image processor: implementation and programming of a
      single channel digital optical circuit.
AB  - A diode-laser driven all-optical iterative processor has been constructed and
      tested. Results are presented showing operation equivalent to a single channel of
      the cellular logic image processor architecture. Functional features of the
      circuit include optically programmable logic, thresholding, and data
      synchronization. Essential elements such as cascadability, logic-level
      restoration, and data feedback have been demonstrated with the optical processor
      controlled by a conventional electronic computer. Serial processing algorithms
      for word recognition, comparison, full addition, and subtraction have been
      implemented. Comments on the reliability of operation and future plans for
      expansion are made.

PMID- 20700209
TI  - Photonic switching applications of 2-D and 3-D crossover networks based on 2
      input, 2-output switching nodes.
AB  - Optical implementations of both 2-D and 3-D crossover networks are described, and
      we show that these networks can be used for connecting multiple stages of 2
      input, 2-output switching elements. We also show that simple conversion steps can
      be used to convert 2-D crossover networks into 3-D crossover networks. Both
      network types can be implemented with low loss optical imaging systems, and we
      show that the same optics can be used to implement the intranode connections and
      the internode for various types of 2-input, 2-output switching elements. In
      addition, we discuss the difficulties that arise when the same optical hardware
      is applied to switching elements of larger dimensionality.

PMID- 20700210
TI  - Holographic interconnections in photorefractive waveguides.
AB  - An architecture for implementing large scale holographic interconnections in
      photorefractive waveguides is described. Methods for controlling the hologram
      using unguided light are considered and experimentally demonstrated.

PMID- 20700211
TI  - Design and performance of a multiprocessor system employing board-to-board free
      space optical interconnections: COSINE-1.
AB  - A practical thirty-six processor computer system employing manually
      reconfigurable board-to-board free-space optical interconnections has been built.
      The free-space optical interconnection section employs collimated beams that have
      90 cm of transmission length at the maximum. It acts as a reconfigurable optical
      backplane that accommodates 144 input/output ports. The processors applied to the
      system are Transputers, each of which has four bidirectional links to communicate
      with other Transputers. This paper describes the design concept and the optical
      interconnection performances of the optical interconnection section employed in
      the constructed system.

PMID- 20700212
TI  - Generalized filtering in acoustooptic systems using area modulation.
AB  - We report on a technique for implementing general filtering operations in
      acoustooptic signal processing systems. We use a binary recording method called
      area modulation to reduce linearity problems associated with spatial light
      modulators that operate by controlling the amplitude of light. We present an
      analysis of this method, we report on experiments with an acoustooptic system to
      verify the analysis, using photographic film and a liquid crystal display to
      implement the area modulation masks, and we discuss the limitations of the
      technique.

PMID- 20700213
TI  - Complex amplitude reflectance of the liquid crystal light valve.
AB  - The complex amplitude reflectance of the liquid crystal light valve (LCLV) is
      determined as a function of the writing intensity and applied voltage using an
      approximate model. The input and output polarizers are assumed to have arbitrary
      directions. The theoretical results based on this model match our experimental
      measurements. This theory allows us to optimize the operation of the LCLV as an
      intensity or phase-only spatial light modulator. When the polarizers are
      orthogonal and the input polarizer is at -34 degrees with the front liquid
      crystal director, the intensity reflectance reaches 100% (compared to 81% for the
      conventional configuration). Phase-only modulation is realizable by use of
      appropriate applied voltage bias and configuration of polarizers.

PMID- 20700214
TI  - Color control in reflection holograms by humidity.
AB  - A method is presented which permits control of the reconstruction wavelength of
      reflection holograms and holographic optical elements. This approach makes use of
      developer and bleach which minimize emulsion shrinkage combined with control of
      ambient humidity to control the emulsion shrinkage during formation and
      reconstruction. A simple index matching approach to the elimination of the wood
      grain effect in reflection holograms is also presented.

PMID- 20700215
TI  - Space-variant holographic optical elements in dichromated gelatin.
AB  - Spatially variant holographic optical elements in dichromated gelatin can
      implement many complicated interconnection patterns and networks in a
      straightforward manner. We demonstrate some prototype, high efficiency, point to
      point, off-axis interconnects for replay at the recording wavelength (514.5 nm).
      Design considerations and potential uses in the fields of optical computing and
      optical communications are examined. Finally, we suggest a modified approach
      which allows for on-axis operation and replay in the near infrared.

PMID- 20700216
TI  - Design of substrate-mode holographic interconnects with different recording and
      readout wavelengths.
AB  - A method for recording a substrate-mode holographic interconnect system, composed
      of two identical holographic optical elements (HOEs) which were recorded on the
      same plate, has been developed. Since the possible recording wavelengths for
      efficient holograms are usually different from the readout wavelengths, the
      holographic elements must be recorded with predistorted wavefronts to assure high
      diffraction efficiencies and low aberrations. The predistorted wavefronts are
      derived from simple spherical holograms whose readout geometries differ from
      those used during recording. The method is illustrated with HOEs recorded at 488
      nm and read out at 633 nm. Nearly diffraction-limited imaging and high
      efficiencies were achieved.

PMID- 20700217
TI  - Gray level transformation to increase the density of interferometric fringes.
AB  - A gray level transformation is presented to simulate the interferometric process.
      The transformation uses properties of sinusoidal functions to produce rapidly
      varying intensities from those with nearly zero gradients. The transformation
      when used in conjunction with optical techniques, such as holographic
      interferometry, has the effect of increasing the optical sensitivity and
      producing a large number of fringes where otherwise only a fraction of a fringe
      would be observed. This technique is ideal for holographic analysis of
      deformations in microscopic regions.

PMID- 20700218
TI  - Readout properties of the specklegram recorded in photorefractive Bi(12)SiO(20)
      crystal.
AB  - The readout properties of the specklegram recorded in a photorefractive
      Bi(12)SiO(20) (BSO) crystal plate have been investigated by observing the Young
      fringes and the polarization change of the light transmitted from the BSO plate.
      The Young fringes can be obtained without an analyzer by any linearly polarized
      readout beam; they have higher visibility than those obtained from a photographic
      plate specklegram, since the specklegram recorded in the BSO crystal can be read
      out by the spatial distribution of both the degree of polarization and the
      azimuth angle of polarization. Selective interference of a kind is performed.

PMID- 20700220
TI  - Nasa patter.

PMID- 20700219
TI  - Photoacoustic depth profiling by cross-correlation using a GaAs light emitting
      diode.
AB  - We present a new approach to depth profiling optically opaque multilayered
      samples. The presence of interfaces in a sample is revealed by cross-correlating
      a randomly generated optical probe beam from a GaAs light emitting diode and its
      generated photoacoustic signal. The technique attains a throughput advantage over
      previous profiling methods since it operates without an external optical
      modulator. Random intensity modulation of the light source is achieved by direct
      current modulation of the diode. We show the effectiveness of our technique by
      establishing the double-layer structure of a magnetic tape.

PMID- 20700222
TI  - Applicability of the.Lorentzian peak method to analyze leaky and lossy optical
      waveguides.
AB  - Several conclusions concerning the applicability of the Lorentzian peak method to
      compute the complex propagation constant of leaky and lossy waveguide modes are
      established.

PMID- 20700223
TI  - Measuring the tilt angle of a single-mode optical fiber endface: a novel method.
AB  - The tilt angle of a single-mode optical fiber endface is successfully measured
      with high accuracy by observing the far field intensity distribution of the
      guided beam.

PMID- 20700224
TI  - Single-mode fiber diameter measurements using Lloyd's mirror.
AB  - An interferometric method for measurement of the fiber outside diameter with an
      uncertainty of <1 microm is proposed and experimentally demonstrated. The fringe
      pattern produced by placing the fiber in contact with a reflecting surface is
      utilized.

PMID- 20700225
TI  - Single-mode optical fiber ring and loop resonators using degenerate two-wave
      mixing.
AB  - Single-mode optical fiber ring (or loop) resonator utilizing degenerate two-wave
      mixing is proposed. The degenerate two-wave mixing can bring the fiber ring into
      full resonance and enhance the finesse or amplify the output intensity and change
      its characteristic from being of the channel-blocking to channel-passing type.

PMID- 20700226
TI  - B? X transitions in Hgl caused by collisions of N(2)(+) -CO(+) ions with Hgl(2)
      molecules.
AB  - Collision-induced dissociative excitation reactions involving collisions of
      N(+)(2) and CO(+) ions and HgI(2) molecules have been studied in the kinetic
      energy range of 100-1000 eV (laboratory frame). Emission spectra from the B ? X
      transition of the HgI radical as well as atomic mercury lines from various highly
      excited energy levels have been observed and analyzed. Emission cross sections of
      the most intense molecular band of the HgI([Equation]) transition at 445 nm have
      been determined.

PMID- 20700227
TI  - Pressure shifts of O(3) broadened by N(2) and O(2).
AB  - High resolution infrared spectra of O(3) have been recorded with an FT
      spectrometer at Reims University with a resolution of 0.002 cm(-1) and a SNR of
      the order of 800. The 2100-cm(-1) region corresponding to the v(1) + v(3) band
      has been analyzed. A large number of spectra, with ozone pressure varying from 5
      to 50 Torr and foreign gas from 80 to 700 Torr, were recorded. The CO lines were
      recorded simultaneously and used as the standard to obtain the shifts, which have
      been measured for about 150 lines. We note a linear variation of the shifts with
      the J quantum number.

PMID- 20700228
TI  - Positive pulse switching in coupled nonlinear Fabry-Perot cavities.
AB  - It is shown that positive pulse switching is possible in a system of two coupled
      nonlinear Fabry-Perot cavities. The conditions in which a signal beam can be
      switched on and off by positive pulses in the steady state regime are described
      for cavities filled with Kerr media having a long diffusion length.

PMID- 20700229
TI  - Propagation of a generalized radiance in paraxial optical systems.
AB  - It is demonstrated that the symmetric form of the generalized radiance remains
      invariant on propagation along rays through lossless paraxial optical systems
      described by their ABCD matrices. This result is derived directly on the basis of
      the cascaded Huygens-Fresnel integral, and it holds for all states of the field
      coherence. When combined with quasihomogeneous sources the result leads to a
      fully consistent wave theory of radiometry with partially coherent light.

PMID- 20700230
TI  - Numerical investigation of a three-mirror resonator for a TE CO(2) laser.
AB  - A numerical model of a three-mirror resonator for a TE CO(2) laser was developed.
      This model was used to determine if a three-mirror resonator with an etalon could
      be used to ensure tunable single-mode action on the lower gain lines of CO(2).
      Single-mode pulse energies were also predicted and good agreement was found with
      experimentally measured values. An analysis of the thermal frequency drift of the
      resonator is also presented.

PMID- 20700231
TI  - Gain enhancement by signal beam chopping for two-wave coupling with a BSO
      crystal.
AB  - Gain enhancement via signal beam chopping for two-wave coupling with a
      Bi(12)SiO(20) crystal is demonstrated. In this method the gain of a two-wave
      coupling scheme is increased using a transient effect. This effect is created
      during the grating formation due to the phase difference between the interference
      fringe of the light intensity incident on the crystal and the photoinduced
      refractive index fringe in the crystal. The maximum gain of 11.7 was achieved
      with an applied electric field of 6.0 kV/cm, a fringe spacing of 29.5 microm, a
      beam intensity ratio of 1240, and a chopping frequency of 6.0 Hz. This gain is
      nearly as high as that obtained with the moving interference-fringe method
      proposed by Huignard and Marrakchi. The gain enhancement using the transient
      effect caused by the polarization rotation of the signal beam (using a rotating
      halfwave plate) is also described. Preliminary experimental results are shown.

PMID- 20700232
TI  - Photorefractive effects in tantalum-doped potassium niobate.
AB  - Photorefractive gain is measured in poled 1% tantalum-doped potassium niobate
      (KNbO(3)). Two-wave mixing experiments are presented which exploit the r(42)
      coefficient of KNbO(3) by employing nonsymmetric geometries which rotate the
      grating vector away from the optic axis. The effect of this rotation on the
      exponential gain coefficient is shown. Experimental results are compared to an
      analytic expression derived for this parameter. The experiments were performed
      using an argon laser stabilized at lambda = 514.5 nm. The light was
      extraordinarily polarized, and the beams were incident on the b-face of the
      crystal. The absorption and the response time of the crystal were measured.
      Losses due to scattering and phase conjugation were also investigated.

PMID- 20700233
TI  - Light propagation characteristics for arbitrary wavevector directions in biaxial
      media by a coordinate-free approach.
AB  - The general case of light propagation in lossless anisotropic media occurs in
      crystals that are biaxial, either naturally so or by induced means (e.g., by
      electrooptic effect). In these crystals the optical properties, such as the
      refractive indices, change with propagation direction and are conveniently
      described by the two-sheeted wavevector surface. Most published work treats light
      propagation only in the principal planes of the crystal, where the wavevector
      surface reduces to a circle and an ellipse and the mathematics is simplified.
      Commonly, however, a biaxial bulk or waveguide device, especially an active
      device, will be oriented so that the light propagation is not in a principal
      plane. A complete and concise coordinate-free approach is presented for isolating
      each sheet, thereby providing a convenient means for calculating the directional
      optical properties of the two decoupled waves for arbitrary wavevector directions
      and birefringence levels. The versatility of this approach coupled with available
      graphics software is demonstrated by displaying numerous cross sections of the
      wavevector surfaces.

PMID- 20700234
TI  - High resolution tuning system for pulsed dye lasers.
AB  - A prism placed at the minimum deviation angle inserted into a dye laser cavity
      acts as an optical reductor of the variation of the angle between the tuning
      mirror and the grating, thus facilitating the mechanical requirements to obtain a
      high resolution (0.15-pm) wavelength scan.

PMID- 20700235
TI  - Characteristics of 1, 1',3,3,3',3'-hexamethylindotricarbocyanine iodide as a
      tunable dye laser in the near infrared.
AB  - We describe the lasing characteristics of a 1,1',3,3,3',3'
      hexamethylindotricarbocyanine iodide infrared dye laser. The absorption spectrum
      of the dye dissolved in ethanol has a large peak centered at 744 nm. The
      fluorescence exhibits a Stokes shift of approximately 36 nm with a lifetime of
      1.7 +/- 0.3 ns. For dye laser pumping at 587 nm the laser threshold was 0.3 mJ,
      and the slope efficiency was 22% at the central lasing wavelength of 807 nm. The
      effect of various loss mechanisms is also discussed.

PMID- 20700236
TI  - Transient population dynamics in flashlamp pumped sensitized erbium glass lasers.
AB  - Erbium population dynamics in ytterbium sensitized phosphate glass is studied by
      measuring transient changes in laser probe transmission during flashlamp pumping.
      The influence of energy loss channels such as excitation cumulation and nonlinear
      fluorescence quenching on the flashlamp pumping efficiency is observed to be
      relatively small. The decrease of the pumping efficiency at high input energies
      can be attributed mostly to the blue shift in the flashlamp output radiation
      spectrum.

PMID- 20700237
TI  - Tunable diode-laser-pumped solid state LNA laser for helium spectroscopic
      experiments.
AB  - We have designed, built, and tested a compact, integrated, single-mode solid
      state LNA laser pumped by a semiconductor laser array for exciting the He
      resonance line at lambda = 1.083 microm. The laser's three major components are
      mounted on a single aluminum base, and the diode laser and its beam shaping
      optics are mounted on a separate stage. This compact and stable structure
      provides good frequency stability and nearly pure TEM(00) transverse mode
      operation. The laser can be tuned around the metastable He resonance transition
      in a single longitudinal mode with linewidth congruent with 5 MHz using a solid,
      60% coated intracavity 0.25-mm thick etalon. Saturated absorption signals on this
      transition have been used to measure the stability and tuning range. We have
      measured the properties for several crystals and calculated the expected
      performance characteristics to compare with the measured ones.

PMID- 20700238
TI  - Spatiospectral and picosecond spatiotemporal properties of a broad area operating
      channeled-substrate-planar laser array.
AB  - Spatiospectral and spatiotemporal properties of an eight-element channeled
      substrate-planar laser array are investigated in both cw and pulsed operating
      conditions. The closely spaced CSP array with strong optical coupling between
      array elements is characterized by a broad area laserlike operation determined by
      its spatial mode spectra. The spatiotemporal evolution of the near and far field
      exhibits complex dynamic behavior in the picosecond to nanosecond domain.
      Operating parameters for the laser device have been experimentally determined.
      These results provide important information for the evaluation of the dynamic
      behavior of coherent semiconductor laser arrays.

PMID- 20700239
TI  - Coupling of high power laser diode optical power.
AB  - This paper describes the characteristics of optical couplers with high power
      laser diodes as sources. The couplers investigated include gradient-index (GRIN)
      lenses manufactured by Nippon Sheet Glass, a plano-convex lens, a prism, optical
      fibers manufactured by Ensign-Bickford and Nippon Sheet Glass, and fiber optic
      stub manufacture by Spec Tran. The characteristics measured included: (1) GRIN
      lens transmission of up to 97%, fiber transmission of up to 90%, plano-convex
      lens transmission of up to 92%; (2) intensity distribution contours and profiles
      of the beam transmitted through GRIN lenses and optical fibers; (3) the beam
      dimensions of a collimating system; and (4) the divergence of optical fibers of
      varying lengths. Spectra Diode Laboratory and McDonnell Astronautics Company/Opto
      Electronics Center manufactured the laser diodes sources that emitted up to 3.6
      W.

PMID- 20700240
TI  - Optimization and characterization of a high repetition rate, high intensity
      Nd:YLF regenerative amplifier.
AB  - Solid state regenerative amplifiers have proved to be a reliable source for
      producing stable millijoule pulses as short as a few picoseconds at repetition
      rates ranging from a few hertz to several kilohertz. Here we report on the
      operation of a cw pumped Nd:YLF regenerative amplifier that uses a convex-concave
      design to optimize output energy and stability while minimizing the energy
      density on critical intracavity optical components. The amplifier yields stable 5
      mJ 40-ps pulses at 700 Hz and has achieved 1-mJ output at a 3.5-kHz repetition
      rate. Results and analysis of the beam profile and contrast ratio for this system
      are also presented. Our results are contrasted to the general design
      considerations of regenerative amplifiers.

PMID- 20700241
TI  - Modified Gaussian approach for the design of optical fiber couplers of arbitrary
      core shapes.
AB  - Many fiber devices, e.g. fiber couplers, rely on the cladding evanescent field
      for their operation. We present a new method for determining the approximate
      fundamental mode fields, with particular reference to cladding field
      applications. In our method, by introducing a field which is accurate both near
      to and far from the core axis, coupling parameters in fiber couplers can be
      obtained in a simple form. We apply this to studies of couplers consisting of two
      identical cores of arbitrary shape. We have compared the results from the new
      approximation with those from the usual Gaussian in circular core cases where
      exact solutions can be found and have shown that the new approximation can give
      more accurate propagation constants and, especially, fundamental mode fields. The
      evanescent behavior of these fields is directly related to the coupling features
      of a fiber coupler. In particular, we apply this new method to twin elliptic core
      fibers to quantify their polarization transmitting and polarization coupling
      characteristics. Up to now, as far as we know, no method has seemed appropriate
      to handle this system. Design features of birefringent and polarization coupling
      of these fibers for device applications are also discussed.

PMID- 20700242
TI  - Output saturation in a 980-nm pumped erbium-doped fiber amplifier.
AB  - A fiber amplifier model is developed which includes a finite lifetime for the
      pumped level. Pump excited state absorption (ESA) from the pumped level is also
      included. The model is solved numerically for a erbiumdoped fiber amplifier
      pumped at 980 nm. The signal output power at 1.5 microm is found to be limited by
      the finite lifetime of the (4)I(11/2); ESA of the pump from the (4)I(11/2)
      further limits the signal output. Lifetimes of the (4)I(11/2) were measured for
      Er(3+) in a series of oxide and fluoride glasses. Output saturation is most
      important in the fluoride based glasses, where the (4)I(11/2) lifetime is
      longest.

PMID- 20700243
TI  - Fabrication and characterization of dye doped polyester-polyurethane optical
      waveguides.
AB  - A systematic study of the fabrication and characterization of planar optical
      waveguides based on polyester-polyurethane coatings was done. Mode effective
      refractive index measurements were performed on a large number of these
      waveguides fabricated on glass substrates prepared in different conditions. The
      results indicate that the effect of the dye is to increase the refractive index
      of the waveguides. The losses in the guides, however, initially decreased from
      0.9 to approximately 0.5 dB/cm when the dye concentration was approximately 0.1%
      but increased drastically (>30 dB/cm) for guides with greater dye concentrations.

PMID- 20700244
TI  - Achromatic waveguide lenses.
AB  - An investigation of the chromatic properties of waveguide lenses is described. In
      general, the focal length of mode-index and Fresnel zone (diffractive) lenses
      will be a function of wavelength. As a result, these lenses will have high
      optical quality over only a relatively small wavelength range. A method is given
      to correct for this chromatic dispersion by forming a hybrid mode
      index/diffractive doublet. Using this approach, the various lens parameters can
      be chosen so that the chromatic dispersion of the diffractive element will cancel
      the dispersion of the refractive element. In certain conditions, the power of the
      diffractive element in the hybrid achromatic doublet can be shown to go to zero
      producing an achromatic mode-index lens. It was found that, with typical
      waveguide materials, a 10-mm focal length, f/5 hybrid mode-index/diffractive lens
      can be made that has a usable wavelength range of approximately 80 nm. This is
      over an order of magnitude improvement compared with that obtained with
      conventional mode-index and diffractive lens types.

PMID- 20700245
TI  - Direct measurement of the effective refractive indices of GaAs/AIGaAs slab
      waveguides: a new technique.
AB  - A new method is presented for accurately and nondestructively measuring the
      effective refractive indices of GaAs slab waveguides. The experimental setup is
      extremely simple. This method is particularly applicable for buried waveguides
      and high refractive index waveguides that cannot be measured by prism couplers.
      It is also suitable for glass and LiNbO(3) waveguides.

PMID- 20700246
TI  - Large aperture cube corner interferometer with a resolution of 0.001 cm(-1).
AB  - The interferometer of the Fourier transform spectrometer at the University of
      Oulu has been modified so that the maximum instrumental resolution is better than
      10(-3) cm(-1). The resolution of the previous interferometer was 4.5 x 10(-3) cm(
      1). The present interferometer consists of large cube corner mirrors and a large
      Mylar beam splitter. Each corner mirror has been made with three flat mirrors on
      an adjustable supporting frame. The interferometer was already in practical use
      in 1985. The first spectra (H(2)O, CO(2), N(2)O, OCS) recorded on this
      interferometer have been presented in HANDBOOK OF INFRARED STANDARDS WITH
      SPECTRAL MAPS AND TRANSITION ASSIGNMENTS BETWEEN 3 AND 2600 microm, G.
      Guelachvili and K. Narahari Rao, Eds. (Academic, New York, 1986).

PMID- 20700247
TI  - Photomultiplier for optically probing Comet Halley.
AB  - A low mass eight-color channel photopolarimeter was developed for the Giotto
      spacecraft. Utilizing the spin of the spacecraft, a multichannel plate
      photomultiplier, and a unique optical design, the instrument required no moving
      parts to measure color and linear polarization. The photopolarimeter collected
      data as the spacecraft passed through the coma of Comet Halley on 13 and 14 Mar.
      1986. This instrument's design, calibration, and reduction are discussed and some
      final results are presented.

PMID- 20700248
TI  - Laser Doppler flowmetry: measurements in a layered perfusion model and Monte
      Carlo simulations of measurements.
AB  - Fluid flow in a flow model was measured with a laser Doppler flowmeter normally
      used for tissue perfusion measurements. The flow parameter is deduced from the
      first moment of the spectral power density of intensity fluctuations at a
      detector viewing the model, which is illuminated by a laser. The model consisted
      of layers, filled with liquid, containing scattering particles, at different
      distances to the optics of the flowmeter. To each of the layers a flow can be
      applied. The configuration of the optical components could be varied, which
      resulted in an adjustable relative sensitivity for the flow in the different
      layers. Here, the feasibility of depth-dependent flowmetry with the laser Doppler
      flowmeter is shown experimentally. The measurements in the flow model were
      simulated with Monte Carlo calculations. The results indicate that these
      calculations may be of help to interpret experimentally obtained flow results.

PMID- 20700249
TI  - Continuous wave laser absorption techniques for gasdynamic measurements in
      supersonic flows.
AB  - Line-of-sight measurements of velocity, temperature, pressure, density, and mass
      flux were performed in a transient shock tube flow using three laser absorption
      schemes. All methods employed an intracavity-doubled ring dye laser tuned to an
      OH transition in the A(2) summation operator(+) ? X(2)II (0,0) band at 306 nm. In
      the first scheme, the gas was labeled by 193.3-nm excimer photolysis of H(2)O,
      and the passage of the generated OH was detected downstream. In the second
      method, the laser was tuned at a rate of 3 kH(z) over the R(1)(7) and R(1)(11)
      line pair, and absorption was simultaneously monitored at 90 and 60 degrees with
      respect to the flow. Velocity was determined from the Doppler shift of the
      profiles and the temperature from the intensity ratio of the lines. Pressure was
      determined from both the magnitude of absorption and the collisional broadening.
      In the third method, the laser wavelength was fixed at a single frequency, and a
      continuous measurement of velocity and pressure was obtained using the signals
      from the two beam paths. All methods gave results which compare favorably to
      calculated values.

PMID- 20700250
TI  - Optimal heterodyne detector array size for 1-microm coherent lidar propagation
      through atmospheric turbulence.
AB  - The heterodyne detection efficiency for a 1-microm coherent atmospheric
      backscatter lidar was numerically calculated using a Monte Carlo technique which
      included a simple model for the effects of atmospheric turbulence. The results
      show that the heterodyne detection efficiency of a single-element detector is
      severely reduced by the effects of atmospheric turbulence, but that the use of an
      appropriate sized, multiple-element heterodyne detector array can overcome these
      effects. In addition, the statistical fluctuation (signal-to-noise ratio) of the
      lidar signal was also calculated and showed that the use of a heterodyne detector
      array can increase the accuracy to that for direct detection.

PMID- 20700251
TI  - Heterodyne Doppler 1-microm lidar measurement of reduced effective telescope
      aperture due to atmospheric turbulence.
AB  - We performed an experimental study on the effect of atmospheric turbulence on
      heterodyne and direct detection lidar at 1 microm, employing a pulsed Nd:YAG
      bistatic focused beam lidar that permitted simultaneous heterodyne and direct
      detection of the same lidar returns. The average carrier-to-noise ratio and
      statistical fluctuation level in the lidar return signals were measured in
      various experimental and atmospheric conditions. The results showed that
      atmospheric turbulence could reduce the effective receiver telescope diameter of
      the l-microm heterodyne lidar to <5cm at a relatively short range of
      approximately 450 m near the ground. The observed effective telescope aperture
      and heterodyne detection efficiency varied during the day as the atmospheric
      turbulence level changed. At this time, we are not able to compare our
      experimental lidar data to a rigorous atmospheric turbulence and lidar detection
      theory which includes independently variable transmitter, receiver, and detector
      geometry. It is interesting to note, however, that the observed limitation of the
      effective receiver aperture was similar in functional form with those predictions
      based on the heterodyne wavefront detection theory by D. L. Fried [Proc. IEEE 55,
      57-67 (1967)] and the heterodyne lidar detection theory for a fixed monostatic
      system by S. F. Clifford and S. Wandzura [Appl. Opt. 20, 514-516 (1981)]. We have
      also applied such an effective receiver aperture limitation to predict the system
      performance for a heterodyne Ho lidar operating at 2 microm.

PMID- 20700252
TI  - Raman shifting of KrF laser radiation for tropospheric ozone measurements.
AB  - The differential absorption lidar (DIAL) measurement of tropospheric ozone
      requires use of high average power ultraviolet lasers operating at two
      appropriate DIAL wavelengths. Laboratory experiments have demonstrated that a KrF
      excimer laser can be used to generate several wavelengths with good energy
      conversion efficiencies by stimulated Raman shifting using hydrogen (H2) and
      deuterium (D(2)). Computer simulations for an airborne lidar have shown that
      these laser emissions can be used for the pecise (less than 5% random error) high
      resolution (200-m vertical, 3-km horizontal) measurement of ozone across the
      troposphere using the DIAL technique. In the region of strong ozone absorption,
      laser wavelengths of 277.0 and 291.7 nm were generated using H(2) and D(2),
      respectively. In addition, a laser wavelength at 302.0 nm was generated using two
      cells in series, with the first containing D(2) and the second containing H(2).
      The energy conversion efficiency for each wavelength was between 14 and 27%.

PMID- 20700253
TI  - Continuous wave coherent laser radar: calculation of measurement location and
      volume.
AB  - The SNR equation of a CW, monostatic, coherent laser radar system is examined for
      the case of a distributed aerosol target. General analytic equations are derived
      which explicitly describe the contribution to total SNR from each range interval
      along the optic axis, the range resolution of the measurement, and the
      atmospheric volume contributing to the measurement. Plots are presented showing
      the location in range and the volume of the laser radar measurement.

PMID- 20700254
TI  - Enhancement of backscattered intensity for a bistatic lidar operating in
      atmospheric turbulence.
AB  - The extended Huygens-Fresnel formulation is used to calculate the enhanced
      backscattered intensity as a function of the off-axis receiver distance for a
      bistatic lidar operating in atmospheric turbulence. The result is simple and
      compact and allows the regime where there is significant enhancement to be
      readily identified. In addition, the result depends only on the logamplitude
      covariance, which implies that the enhancement is due to incoherent turbulence
      perturbation effects.

PMID- 20700256
TI  - Patents.
AB  - 4,856,887; 4,904,035; 4,980,536; 4,984,857; 4,984,892; 4,985,624; 4,986,641;
      4,984,878.

PMID- 20700255
TI  - Simple empirical model of the oceanic point spread function.
AB  - The point spread function (PSF) is an important property for predicting beam
      propagation and imaging system performance. Measurements of the PSF in three
      different locations (Pacific Ocean, Tongue of the Ocean, and Sargasso Sea) are
      presented. These measurements are used to validate extensive laboratory
      measurements [S. Q. Duntley, "Underwater Lighting by Submerged Lasers and
      Incandescent Sources," SIO Ref. 71-1, Scripps Institution of Oceanography, U.
      California, San Diego (1971)]. In all three locations a simple exponential
      expression describes the angular variation of the PSF in the 4-100-mrad range.
      The exponent in this relationship has a simple location specific dependence on
      attenuation length and the ratio of the absorption to beam attenuation
      coefficient. These relationships can be used to predict the PSF for an arbitrary
      path length.

PMID- 20700257
TI  - Microlenses in polymethyl methacrylate with high relative aperture.
AB  - Lens arrays with relative apertures as high as 1 can be fabricated in polymethyl
      methacrylate with a high-energy H+b eam and diffusion of styrene in the
      irradiatedd omains.

PMID- 20700258
TI  - Fiber-optic scrambler reduces the bandpass range dependence of Fabry-Perot
      etalons used for spectral analysis of lidar backscatter.
AB  - Lidar systems that analyze backscatter with Fabry-Perot etalons exhibit range
      dependent spectral transmission functions. A fiber-optic scrambler is described
      that reduces this range dependence.

PMID- 20700259
TI  - Phosphor-based thermometry of the rotor in a high-power electrical generator.
AB  - A prototype on-line rotor temperature monitor based on phosphor decay-time
      measurements using optical fibers was tested on two large electrical generators.

PMID- 20700260
TI  - Using coherent anti-Stokes Raman spectroscopy to probe the temperature field of a
      combusting droplet stream.
AB  - We describe measurements using coherent anti-Stokes Raman scattering (CARS) of
      the local temperature field near a combusting droplet stream. Synchronizing the
      CARS measurements with the droplets in the stream permits correlations between
      the temperature field and the droplet position.

PMID- 20700261
TI  - Design of a wide field diffractive landscape lens: comment.

PMID- 20700262
TI  - Parameters of spinning AM reticles.
AB  - A new method of obtaining amplitude modulation (AM) for determining target
      location with spinning reticles is presented. The method is based on the use of
      graded transmission capabilities. The AM spinning reticles previously presented
      were functions of three parameters: amplitude vs angle, amplitude vs radius, and
      phase. This paper presents these parameters along with their capabilities and
      limitations and shows that multiple parameters can be integrated into a single
      reticle. It is also shown that AM parameters can be combined with FM parameters
      in a single reticle. Also, a general equation is developed that relates the AM
      parameters to a reticle transmission equation.

PMID- 20700263
TI  - Efficient optical elements to generate intensity weighted spot arrays: design and
      fabrication.
AB  - We report on the design and fabrication of fully 2-D surface relief diffraction
      elements that can split a single collimated beam into many beams in an arbitrary
      intensity distribution. These splitters were designed by computer using simulated
      annealing, and made into phase gratings by electron-beam lithography followed by
      plasma etching into quartz glass. Both two and four phase level gratings have
      been fabricated, allowing a wide range of uniform and weighted spot patterns to
      be generated. These grating elements have a measured diffraction efficiency of
      over 74%, with the beam intensity ratios accurate to within 1% of their target
      values.

PMID- 20700264
TI  - Optical characterization of a four-medium thin film structure by real time
      spectroscopic ellipsometry: amorphous carbon on tantalum.
AB  - A real time spectroscopic ellipsometry (RTSE) investigation is reported for
      comprehensive optical characterization of a thin film/substrate system, vacuum
      deposited hydrogenated amorphous (diamondlike) carbon on tantalum. Precision RTSE
      measurements were carried out from 1.6 to 4.0 eV with a time resolution of 3 s
      and a repetition period of 15 s. Spectra collected during substrate exposure to
      an Ar(+) beam identify processing conditions for optimum precleaning and provide
      the bulk dielectric function of the Ta. Spectra collected during alpha-C:H growth
      to approximately 1700 A by ion beam deposition are best interpreted with a four
      medium model (Ta/interface/alpha-C:H/ambient). From the analysis, we deduce the
      bulk dielectric function for alpha-C:H and an approximate dielectric function for
      the interface layer, interpreted as a carbide. The time evolution of the bulk and
      interface layer thicknesses is also determined. The dielectric functions of alpha
      C:H deduced assuming a four-medium model and a three-medium model which neglects
      the interface layer differ by as much as 5%. The capabilities of measurement and
      analysis reported here represent a major new advance in the optical
      characterization of thin films.

PMID- 20700265
TI  - Theory of 2-D ion exchange in glass: optimization of microlens arrays.
AB  - The equations of two-component electric field assisted ionic diffusion and
      exchange are formulated analyticallyand solved numerically for the problem of 2-D
      (cylindrical) microlenses in glass, both for individual, isolated microlenses and
      arrays of microlenses. The theoretical formulation represents a proposed
      extension of the 1-D (planar) formulation of Abou el leil and Cooper. Ray tracing
      through computed index of refraction distributions is used to estimate optical
      performance. The inclusion of interactions of neighboring microlenses is shown to
      be important for optimizing optical performance of a high fill factor array.

PMID- 20700266
TI  - Tunable self-reference phase conjugate interferometer.
AB  - We propose a versatile self-reference phase conjugate interferometer which is
      based on degenerate four-wave mixing in a photorefractive crystal. A crystal of
      BaTiO(3) is used to store a wavefront which is compared to its displaced version
      at a later time. Tunable transverse and longitudinal displacements can be easily
      given to a wavefront. A theoretical description and experimental results of this
      interferometer are presented.

PMID- 20700267
TI  - Linear approximation for measurement errors in phase shifting interferometry.
AB  - This paper shows how measurement errors in phase shifting interferometry (PSI)
      can be described to a high degree of accuracy in a linear approximation. System
      error sources considered here are light source instability, imperfect reference
      phase shifting, mechanical vibrations, nonlinearity of the detector, and
      quantization of the detector signal. The measurement inaccuracies resulting from
      these errors are calculated in linear approximation for several formulas commonly
      used for PSI. The results are presented in tables for easy calculation of the
      measurement error magnitudes for known system errors. In addition, this paper
      discusses the measurement error reduction which can be achieved by choosing an
      appropriate phase calculation formula.

PMID- 20700268
TI  - Digital speckle pattern shearing interferometry: limitations and prospects.
AB  - Since shearing interferometry, also called shearography, does not depict fringes
      caused by object tilt, it is a tool well suited for either nondestructive testing
      of objects under load or for quantitative evaluation of flexural strains. In
      traditional shearing interferometry, observation of fringes requires optical
      processing of doubleexposed interferograms. Hence the technique is not in real
      time. This paper explores the possibilities and limitations for real time
      shearing fringe observation using the electronic speckle pattern interferometry
      technique. Prospects for quantitative determination of local tilt and flexural
      strain using the phase shifting technique are commented on, and some preliminary
      results are shown.

PMID- 20700269
TI  - Array generation with lenslet arrays.
AB  - Lenslet arrays can be used as phase gratings, having many diffraction orders with
      equal intensity. Applications are multiple imaging and illumination of arrays of
      optical or optoelectronic devices in digital optics. The homogeneity of the
      intensities within the array can be improved by using field lenslets. The basic
      theory as well as experiments with diffractive and with graded index lenses are
      shown.

PMID- 20700270
TI  - Fast diffraction-limited cylindrical microlenses.
AB  - We describe a technique for fabricating fast well-corrected cylindrical
      microlenses for applications such as collimating laser diodes and coupling light
      into and out of integrated optics devices. The lenses are produced by first
      grinding a glass preform to a desired cross-sectional shape and then heating and
      drawing the preform into a fiber of the desired diameter. The heating and drawing
      operations polish the glass surface and reduce the cross-sectional dimensions but
      maintain the cross-sectional shape. Diffraction-limited 220-microm focal length
      immersion lenses with numerical aperture >0.6 have been demonstrated.

PMID- 20700271
TI  - Analysis of combined moire and laser speckle grating methods used in 3-D crack
      tip deformation measurements.
AB  - The paper provides analyses for two optical schemes developed for mapping 3-D
      crack tip fields in ductile materials. The first scheme combines the in-plane
      moire method with the projection moire method to determine all three displacement
      components simultaneously. In the second method, we combined onebeam laser
      speckle photography with the projection moire method to measure 3-D deformation
      fields. The experimental results obtained using these methods are presented.

PMID- 20700272
TI  - Calculation of area change and volume displacement from moire topograms of
      deformed membranes.
AB  - A method is proposed to calculate the area change and the volume displacement of
      a deformed membrane from the measurement of its displacement amplitude on a
      regular grid of observation points. The method is demonstrated on a circular
      latex membrane deformed by air pressure. The displacement data are obtained by
      phase shift moire interferometry. Area changes down to 0.5% and volume changes
      down to 16.1 mm(3) are measured, and error flags are determined.

PMID- 20700273
TI  - Physics of loose abrasive microgrinding.
AB  - This study examined the physics of loose abrasive microgrinding (grinding with
      micron and submicron sized abrasives). More specifically, it focused on the
      transition from brittle to ductile mode grinding which occurs in this region of
      abrasive sizes. Process dependency on slurry chemistry was the primary area of
      emphasis and was studied for diamond abrasives varying in size from 3.0 to 0.75
      microm on both ULE and Zerodur, with emphasis on ULE. Ductile mode grinding was
      achieved with smaller abrasives, as expected, however two significant discoveries
      were made. The first observation was that by simply changing slurry chemistry, it
      was possible to induce the transition from brittle fracture to ductile mode
      grinding in ULE. This transition point could be intentionally moved about for
      diamonds 3.0-0.75 microm in diameter. For any given abrasive size within these
      limits, either brittle fracture or ductile removal may be achieved, depending on
      the slurry used to suspend the diamonds. Several slurries were studied, including
      water, a series of homologous n-alcohols, and other solvents chosen for
      properties varying from molecular size to dielectric constant and zeta potential.
      The study revealed that this slurry dependency is primarily a Rebinder effect.
      The second finding was that a tremendous amount of surface stress is introduced
      in loose abrasive ductile mode grinding. This stress was observed when the Twyman
      Effect in ULE plates increased by a factor of 4 in the transition from the
      brittle to the ductile mode. An assessment of the cause of this stress is
      discussed.

PMID- 20700274
TI  - Optical properties of parylene and its use as substrate in beam splitters.
AB  - The optical properties of a commercial parylene pellicle are obtained using a
      classical oscillator model with a single oscillator. Using a standard design
      antireflection stack and beam-splitter multilayer films coated on this pellicle,
      its performance is greatly improved, flattening the curve and increasing its
      useful spectral range.

PMID- 20700275
TI  - Optical properties of vanadium dioxide and vanadium pentoxide thin films.
AB  - Several oxides of vanadium undergo a transition from a semiconductor or
      insulating state to a metal phase at a critical temperature. Vanadium dioxide
      undergoes this transition near 68 degrees C, while V(2)O(5) undergoes a similar
      phase transition near 257 degrees C. During the transition a change in oxide
      crystal structure is accompanied by large changes in electrical and optical
      behavior. Thin films of vanadium oxides are capable of reversibly switching from
      the semiconductor to the metallic state at high speeds and with high spatial
      resolution. Therefore, these oxides have potential use, particularly in thin film
      form, for a wide variety of applications involving thermally activated electronic
      or optical switching devices. Such films are of considerable technical interest
      because of applications in chemical sensors, energy-conserving coatings,
      transparent conductors, and switching materials. The numerous potential
      electronic, optical, and optoelectronic device applications which have been
      suggested have stimulated work on the preparation of thin films by a variety of
      techniques, including chemical vapor deposition, solgel, evaporation, and sputter
      deposition. This paper reviews the optical properties of vanadium oxide coatings
      and stresses the dependence of film properties on sample preparation and
      resultant film microstructure.

PMID- 20700276
TI  - Thin film interference optics for imaging the O II 834-A airglow.
AB  - Normal incidence thin film interference mirrors and filters have been designed to
      image the O II 834-A airglow. It is shown that MgF(2) is a useful spacer material
      for this wavelength region. The mirrors consist of thin layers of MgF(2) in
      combination with other materials that are chosen to reflect efficiently in a
      narrow band centered at 834 A. Peak reflectance of 60% can be obtained with a
      passband 200 A wide. Al/MgF(2)/Si and Al/MgF(2)/SiC interference coatings have
      been designed to reflect 834 A and to absorbe the intense H I 1216 A airglow. An
      In/MgF(2)/In interference filter is designed to transmit 834 A and attenuate 1216
      A radiation. Interference photocathode coatings for rejecting 1216 A radiation
      are also discussed.

PMID- 20700277
TI  - Determination of thin film optical parameters from photometric measurements: an
      algebraic solution for the (T,R(f),R(b)) method.
AB  - A new method of analysis for the simultaneous determination of the optical
      constants and the thickness of thin films is proposed. It requires measurements
      under normal incidence of the transmission and of the reflections from both sides
      of a thin film deposited on a nonabsorbing sbstrate. An algebraic inversion
      technique is developed involving a numerical interpolation procedure in the last
      step. There are no missing solutions. The physical solution can be isolated by a
      comparison with some film thickness estimates or by measurements in a wavelength
      range.

PMID- 20700278
TI  - Transmission ellipsometry on transparent unbacked or embedded thin films with
      application to soap films in air.
AB  - The ratio rho(t) = T(p)/T(s) of the complex amplitude transmission coefficients
      for the p and s polarizations of a transparent unbacked or embedded thin film is
      examined as a function of the film thickness-to-wavelength ratio d/lambda and the
      angle of incidence Phi for a given film refractive index N. The maximum value of
      the differential transmission phase shift (or retardance), Delta(t) = argrho(t),
      is determined, for given N and Phi, by a simple geometrical construction that
      involves the iso-Phi circle locus of rho(t) in the complex plane. The upper bound
      on this maximum equals arctan{[N - (1/N)]/2} and is attained in the limit of
      grazing incidence. An analytical noniterative method is developed for determining
      N and d of the film from rho(t) measured by transmission ellipsometry (TELL) at
      Phi = 45 degrees . An explicit expression for d Delta(t) of an ultrathin film,
      d/lambda << 1, is derived in product form that shows the dependence of Delta(t)
      on N, Phi, and d/lambda separately. The angular dependence is given by an
      obliquity factor, f(0)(Phi) = 2((1/2)) sinPhi tanPhi, which is verified
      experimentally by TELL measurements on a stable planar soap film in air at lambda
      = 633 nm. The singularity of f(0) at Phi = 90 degrees is resolved; Delta(t) is
      shown to have a aximum just short of grazing incidence and drops to 0 at Phi = 90
      degrees . Because N and d/lambda are inseparable for an ultrathin film, N is
      determined by a Brewster angle measurement and d/lambdais subsequently obtained
      from Delta(t) Finally, the ellipsometric function in reflection rho(r) is related
      to that in transmission P(t).

PMID- 20700279
TI  - Optical constants of very thin gold films in the soft x-ray region.
AB  - The optical constants, delta = 1 - n and k, of very thin gold films have been
      determined from the reflectance data obtained in the soft x-ray region of 60-900
      eV. The gold films were prepared to various thicknesses, d = 49 - 270 A, by ion
      beam sputtering (IBS) and electron beam evaporation (EB). A plane parallel slab
      model with due considerations for the surface and the interface roughness was
      employed to analyze the reflectance data by least-squares curve fitting. The
      optical constants determined for the IBS samples definitely show their dependence
      on the film thickness. It is also found that delta of the 201-A thick IBS film is
      smaller by 10% than that of the EB film of 212 A thick.

PMID- 20700280
TI  - Applied optics.

PMID- 20700281
TI  - Information for contributers.

PMID- 20700282
TI  - Binary encoding of gray scale nonlinear joint transform correlators.
AB  - A nonlinear joint transform correlator is described where the joint power
      spectrum, transformed by various degrees of nonlinearity, is represented in a
      binary format using a multiple level threshold function.

PMID- 20700283
TI  - Wavefront reconstruction using iterative Fourier transforms.

PMID- 20700284
TI  - Optoelectronic associative memory using an advanced optical neurochip.
AB  - A drastic improvement in the performance of the associative memory was achieved
      using an optical neurochip. The experimental recognition rate agreed well with
      computer simulation for the associative memory.

PMID- 20700285
TI  - Holographic reproduction of a diffraction-free beam.
AB  - A high resolution Bessel function profile diffraction-free beam has been
      reproduced from a holographic optical element made by direct physical
      interference.

PMID- 20700286
TI  - Two-dimensional grating interferometric imaging of a near object by computed
      tomography.
AB  - The Fourier coefficients of a near object can be obtained by analyzing the
      interference pattern in an achromatic grating interferometer. Using the
      projection slice theorem, the Fourier plane can be filled and the spatial
      irradiance distribution of a 2-D incoherent object can be reconstructed.

PMID- 20700287
TI  - Optically powered arrays for optoelectronic interconnection networks.
AB  - We describe a novel integrated, optically powered optoelectronic array for use in
      2-D interconnection networks. We discuss a generic optoelectronic processing
      structure and propose two circuit schemes for realizing these interconnect
      arrays. It is shown that optical powering of the array pixel electronics
      considerably reduces the high frequency crosstalk between adjacent array
      elements, leading to improvements in bandwidth by >1 order of magnitude when
      compared with similar conventionally powered systems. Design criteria are
      established for determining the trade-offs between fanout and power dissipation,
      and factors limiting packing density in the optically powered scheme are also
      discussed. We also compare the performance of optically powered optoelectronic,
      conventional optoelectronic and all-optical systems on the basis of bandwidth,
      crosstalk, packing density, and functionality and find that optical powering has
      several advantages for use in advanced system architectures.

PMID- 20700288
TI  - Binary phase Fresnel lenses for generation of two-dimensional beam arrays.
AB  - Two-dimensional arrays of mutually coherent optical beams are needed in
      holographic interconnections for both recording and reading gratings. We analyze
      the use and limitations of binary phase Fresnel lenses to generate beams for
      these applications. Two known techniques of ion beam milling and thin film
      deposition are compared to fabricate such lens arrays in SiO(2) and Si(3)N(4).
      Each lens in the 8 x 8 arrays has a 1.2-mm square aperture with a focal length of
      20 mm. Diffraction of a single argon-ion beam into an 8 x 8 array of highly
      uniform coherent focused beams (with 12-microm spot size) was achieved by the
      lenses with an efficiency of approximately 30% (41% theoretical limit).

PMID- 20700289
TI  - Modeling of the field transfer through thick dielectric lines: use in linewidth
      measurement.
AB  - A numerical method for calculating the optical image of a thick line object is
      presented. It consists of slicing (fictitiously) the object and of analyzing the
      propagation through each elementary slice. The method is first developed for
      coherent light and then generalized for partially coherent illumination. Some
      results are compared with other simulations and with experiments.

PMID- 20700290
TI  - Directional image processing using a pinhole camera with a rectangular aperture.
AB  - This paper describes a new method of directional image processing based on a
      pinhole camera with a rectangular aperture.

PMID- 20700291
TI  - Image intensification with color capability.
AB  - Image intensifiers applied to low light level phenomena provide outputs
      restricted to the color of the output phosphor. In many applications the ability
      to provide an image in color, or even color information, is desirable. A design
      of an intensifier system that can present images in color is described. A
      feasibility demonstration is presented, utilizing an intensified grating
      spectroscope.

PMID- 20700292
TI  - Scale space approach to directional analysis of images.
AB  - In this paper a new technique for directional analysis of linear patterns in
      images is proposed based on the notion of scale space. A given image is
      preprocessed by a sequence of filters which are second derivatives of 2-D
      Gaussian functions with different scales. This gives a set of zero crossing maps
      (the scale space) from which a stability map is generated. Significant linear
      patterns are detected from measurements on the stability map. Information
      regarding orientation of the linear patterns in the image and the area covered by
      the patterns in specific directions is then computed. The performance of the
      method is illustrated through applications to synthetic patters and to scanning
      electron microscope images of collagen fibrils in rabbit ligaments.

PMID- 20700293
TI  - Using the hybrid modulating properties of liquid crystal television.
AB  - The phase modulating capabilities of a commercially available liquid crystal
      television (LCTV) have been investigated and applied to the joint transform
      optical correlator architecture. Operating the LCTV in a phase modulating mode
      requires a much smaller coherent light source while still producing a good joint
      transform power spectrum and good correlation signals.

PMID- 20700294
TI  - Recognition of threaded objects by spatial spectrum analysis.
AB  - An optical processing system for the recognition and sorting of machine screws is
      presented. A theoretical analysis of the diffraction problem is detailed which
      provides a basis for selecting a set of features used in the sorting algorithm.
      These features are used to discriminate between screws based on their diameter
      and thread pitch.

PMID- 20700295
TI  - Nonredundant filters for pattern recognition and orientation estimation of
      rotated images.
AB  - We describe a method to implement the recognition and the orientation
      determination of in-plane rotated images by means of nonredundant correlation
      filters which maximize the number of discernible patterns. The filters are
      computed with the minimum averaged correlation energy algorithm on specifically
      prefiltered reference images, with a view to the foreseen application, to reduce
      the intraclass sensitivity and improve the interclass discrimination. Simulation
      results of the correlation are provided and compared with those obtained with the
      standard minimum averaged correlation energy filters.

PMID- 20700296
TI  - Superfine resolution acoustooptic spectrum analysis.
AB  - We demonstrate the feasibility of 3-D acoustooptic spectrum analysis with
      ultrahigh resolution. Sub-Hertz resolution is achieved by processing over a
      sequence of CCD frames.

PMID- 20700297
TI  - Acquisition of 3-D data by focus sensing utilizing the moire effect of CCD
      cameras.
AB  - A new technique was recently presented for finding the 3-D shape of diffusely
      reflecting object surfaces [Appl. Opt. 27, 4684-4689 (1988)]. The technique is
      based on grid projection with small depth of focus, confocal observation, and
      focus sensing by evaluation of the local grating contrast. In this paper a
      modification of the measuring system is demonstrated that allows the use of a 2-D
      CCD array instead of a vidicon as the detector. In this modification the moire
      effect between the projected grid and the CCD array is utilized. Depth resolution
      is increased, and almost no unwanted moire terms arise in the detector output as
      long as the grating frequency is chosen above the Nyquist frequency of the array.
      The technique can be useful in robot vision.

PMID- 20700298
TI  - Patents.
AB  - 4,910,738; 4,917,455; 4,946,239; 4,962,506; 4,953,954; 4,968,136; 4,971,416;
      4,969,157.

PMID- 20700299
TI  - Nasa patter.

PMID- 20700300
TI  - Measurements of Lorentz air-broadening coefficients and relative intensities in
      the H(2)(16)O pure rotational and v(2) bands from long horizontal path
      atmospheric spectra.
AB  - Lorentz air-broadening coefficients and relative intensities have been measured
      for forty-three lines in the pure rotational band and twenty lines in the v(2)
      band of H(2)(16)O between 800 and 1150 cm(-1). The results were derived from
      analysis of nine 0.017-cm(-1) resolution atmospheric absorption spectra recorded
      over horizontal paths of 0.5-1.5 km with the McMath Fourier transform
      spectrometer and main solar telescope operated on Kitt Peak by the National Solar
      Observatory. A nonlinear least-squares spectral fitting technique was used in the
      spectral analysis. The results are compared with previous measurements and
      calculations. In most cases, the measured pressure-broadening coefficients and
      intensities are significantly different from the values in the 1986 HITRAN line
      parameters compilation.

PMID- 20700301
TI  - Frequency fluctuations of stabilized lasers with anisotropic feedbacks.
AB  - A random phase method is proposed to determine the perturbation of the Allan
      variance of frequency stabilized lasers submitted to optical feedbacks. The role
      of different feedbacks is quantitatively described for both one-oscillating
      eigenstate stabilized lasers and two-oscillating-eigenstate stabilized lasers.
      The importance of the feedback polarization is isolated in each system. In both
      cases, the experimental measurements of the Allan variance and of the peak-to
      peak frequency variations due to a periodic modulation of the feedback phase are
      found to be in agreement with the theoretical predictions.

PMID- 20700302
TI  - Frequency stabilization of a He-Ne laser using lateral stress.
AB  - Frequency stabilization of an internal mirror He-Ne laser by a new simple method
      is reported. In this method, the laser cavity length is modulated by stretching
      the front part of the laser tube using lateral stress; in this way the laser
      cavity length is stabilized on the Lamb dip. The relative frequency stability is
      +/-4.1 x 10(-9) over 1 h or longer.

PMID- 20700303
TI  - Longitudinal pumping of lasers with multistripe laser diodes.
AB  - The conventional method of focusing a multistripe laser diode to end pump a laser
      is collimating the beam, compensating the different beam divergencies parallel
      and perpendicular to the array by a cylindrical lens or a prism pair, and finally
      focusing the beam to a circular spot. We have developed an alternative
      arrangement consisting of a spherical and a cylindrical lens. In essence this
      method images object planes parallel and normal to the array differently. For a
      detailed discussion of the two focusing systems we assume that the pump beam
      consists of a linear array of Gaussian beams. Calculations of the laser threshold
      for both focusing methods are performed to compare the efficiency of the focusing
      arrangements. The experimental realization of our focusing arrangement to pump a
      Nd:glass laser with a multistripe diode yields a threshold of 62 mW and a slope
      efficiency of 22%. The theoretical predictions agree well with experimental data.

PMID- 20700304
TI  - Nonlinear interaction of KrF laser radiation with small water droplets.
AB  - Results have been obtained for the interaction of KrF excimer laser radiation
      (lambda = 248 nm, t(pulse) = 17 ns) with 60-microm diam distilled water droplets
      for irradiance values ranging from 3 to 230 GW/cm(2). Laser images of the droplet
      breakup during the time intervals from 0 to 100 ns indicate that the dynamic
      breakup processes are highly nonlinear. At low irradiance (3 GW/cm(2)) material
      is ejected from both the illuminated and shadow hemispheres of the droplet in
      qualitative agreement with the location of the electric field peaks predicted by
      plane wave Lorenz-Mie theory calculations. As the irradiance is increased, the
      interaction on the shadow hemisphere becomes stronger while the interaction on
      the illuminated hemisphere decreases. This nonlinear behavior is attributed to
      rapid electrical breakdown of the droplet near the shadow surface. The breakdown
      region destroys the ability of the droplet to redirect energy toward the front
      hemisphere of the droplet. Without this mechanism, the localized electric field
      maxima near the illuminated surface of the droplet cannot arise. Measurements
      were also taken of the average material velocities during the time intervals from
      0 to 50 ns after arrival of the high energy pulse. Velocities ranged from 1000
      m/s at 3 GW/cm(2) to 6000 m/s at 230 GW/cm(2).

PMID- 20700305
TI  - Achromatic compensation for integrated optic grating couplers with focused beams.
AB  - Results of a theoretical and experimental investigation into the variation of
      coupling efficiency with incident light wavelength are presented for various beam
      focusing conditions for an integrated optical grating coupler. These results
      indicate that wavelength compensation for grating coupling efficiencies can be
      achieved over several nanometers with focused beams. We also show the correlation
      between width of coupling angle and width of coupling wavelength.

PMID- 20700306
TI  - Time-explicit simulation of wave interaction in optical waveguide crossings at
      large angles.
AB  - The time-explicit finite-difference time-domain method is used to simulate wave
      interaction in optical waveguide crossings at large angles. The wave propagation
      at the intersecting structure is simulated by time stepping the discretized form
      of the Maxwell's time dependent curl equations. The power distribution
      characteristics of the intersections are obtained by extracting the guided-mode
      amplitudes from these simulated total field data. A physical picture of power
      flow in the intersection is also obtained from the total field solution; this
      provides insights into the switching behavior and the origin of the radiations.

PMID- 20700307
TI  - Spectral shift due to source correlation in conventional spectroradiometric
      measurements.
AB  - Keeping in view the recent findings of the spectral shift due to source
      correlation during propagation of light, a study has been undertaken to analyze
      the errors which may be introduced in spectroradiometric measurements.

PMID- 20700308
TI  - Simple interferometer for evanescent field refractive index sensing as a
      feasibility study for an immunosensor.
AB  - We describe a fiber optic interferometric refractive index sensor to illustrate
      that, by using the evanescent field of an optical waveguide, a potentially very
      sensitive determination of changes in the refractive index on the waveguide
      surface can be obtained. These changes can, e.g., be the result of
      immunoreactions. We used a Mach-Zehnder interferometer configuration with a flow
      through cuvette in one arm with a decladded multimode glass fiber of 0.6-mm
      diameter and 2-cm interaction length. The obtained resolution in measuring
      refractive index changes is 1 x 10-(3). We also developed the theory describing
      the sensitivity of this sensor using the modal and the geometrical ray
      description.

PMID- 20700309
TI  - Autofocus system for a surgical CO(2) laser.
AB  - An autofocusing (AF) system for a surgical CO(2) laser has been constructed. It
      controls the distance between the focus position of the drilling radiation with
      respect to the target surface independently of surface indentations or target
      movements. It thus leads to a precision instrument that controls the crucial
      parameter that defines the incision depth. Experiments with gelatin and pork skin
      show that for a given beam power the incision depth is constant within 12%. The
      AF system adjusts to distance variations over a 10-mm range, where without
      autofocusing the drilling depth would drop by 75%. The optical setup is
      implemented in a handpiece that is attached to the end of a surgical mirror arm.
      A frequency doubled Nd:YAG laser beam provides the pilot beam for the distance
      measurement. The distance signal arises from a photometric equilibrium method in
      combination with a spot wobbling technique.

PMID- 20700310
TI  - Response characteristics of the phase Doppler particle analyzer for sizing
      spherical particles larger than the light wavelength.
AB  - A theoretical model, based on the geometrical optics approach, has been developed
      to simulate various aspects of the phase Doppler particle analyzer (PDPA). The
      model has taken into consideration the nonuniform (Gaussian) illumination of the
      particles as they pass through the measurement probe volume. Instrument response
      curves have been generated for various scattering angles by performing spatial
      and temporal integration of the scattered intensity distribution over the
      receiver surface. Experimental and theoretical investigations have established
      the applicability of this instrument to both forward scattered and backscattered
      angles.

PMID- 20700311
TI  - Temperature measurements in flames using thermally assisted laser-induced
      fluorescence of Ga.
AB  - The use of thermally assisted fluorescence (THAF) for temperature measurements
      has been investigated in a laminar, premixed C(2)H(2)/O(2)/Ar flame seeded with
      Ga atoms. Average temperature measurements were made with an uncertainty of less
      than +/-100 K in flames >2150 K and were found to be in agreement with sodium
      line reversal temperature measurements and equilibrium calculations. In both fuel
      rich and lean flames spanning equivalence ratios from 0.75 to 2.0, it was found
      that composition influenced the measured temperatures, resulting in an accuracy
      of +/-100 K over this range of flame conditions. Dilution of the flame with N(2)
      rather than Ar resulted in measured temperatures that were substantially higher
      than the calculated adiabatic flame temperature, indicating that, in this case, a
      partial Boltzmann equilibrium is not established among the collisionally
      populated levels of Ga used for the measurement. These results indicate that THAF
      with gallium as the thermometric species is limited to cases in which an
      inefficient quencher, such as a rare gas, is the primary diluent.

PMID- 20700312
TI  - Diode laser measurements of trace concentrations of ammonia in an entrained-flow
      coal reactor.
AB  - We used a single-mode Pb-salt diode laser to quantify in situ the amount of
      ammonia generated during pyrolysis of pulverized coal in an entrained-flow
      reactor at 1225 K. The combination of wavelength modulation spectroscopy, a
      Herriott style multiple pass cell, rapid wavelength scanning (to eliminate noise
      due to turbulence and vibration) and a novel etalon fringe suppression technique
      provided a minimum detectable absorbance of 2 x 10(-6) (SNR = 1, 1-Hz bandwidth)
      corresponding to 0.04-ppm ammonia at 1225 K. This is a 4-order-of-magnitude
      improvement over CO(2) laser based ammonia detectors and is approximately 2000
      times more sensitive than electrochemical detection methods (for equal
      integration times).

PMID- 20700313
TI  - Use of the Hartman sensor to measure the unisoplanatic wavefront tilt.
AB  - It is shown that the Hartman wavefront sensor can be used to measure the degree
      of unisoplanatism under atmospheric wavefront degradations. The measurements
      conform with theory and show the size of the isoplanatic patch in the object
      space and the coherent distance at the entrance of the pupil plane. These two
      measurements are unequal because of inhomogeneous turbulence. This inhomogeneity
      can be accounted for by using known theory and the height of the line of sight
      above the ground.

PMID- 20700314
TI  - Temperature sensitivity of differential absorption lidar measurements of water
      vapor in the 720-nm region.
AB  - Recently measured properties of water vapor (H(2)O) absorption lines have been
      used in calculations to evaluate the temperature sensitivity of differential
      absorption lidar (DIAL) H(2)O measurements. This paper estimates the temperature
      sensitivity of H(2)O lines in the 717-733-nm region for both H(2)O mixing ratio
      and number density measurements, and discusses the influence of the H(2)O line
      ground state energies E'', the H(2)O absorption linewidths, the linewidth
      temperature dependence parameter, and the atmospheric temperature and pressure
      variations with altitude and location on the temperature sensitivity
      calculations. Line parameters and temperature sensitivity calculations for sixty
      seven H(2)O lines in the 720-nm band are given which can be directly used in
      field experiments. Water vapor lines with E'' values in the 100-300-cm(-1) range
      were found to be optimum for DIAL measurements of H(2)O number densities, while
      E'' values in the 250-500-cm(-1) range were found to be optimum for H(2)O mixing
      ratio measurements.

PMID- 20700315
TI  - Influence of cirrus clouds on the VISSR atmospheric sounder-derived sea surface
      temperature determinations.
AB  - Using a more realistic cirrus cloud model, the characteristics of transmittance,
      emittance, and optical thickness and their relationships to cirrus in a diverse
      set of cases are studied by solving the equation of transfer of IR radiation. The
      doubling method is employed in the multiple scattering calculation. The satellite
      observed brightness temperatures for different cases are computed, and stepwise
      regression analyses are performed to yield retrieval equations for sea surface
      temperature (SST). It is shown that the radiative properties of cirrus depend
      strongly on particle concentration, thus on the optical thickness of clouds. For
      clear atmospheres, channel 8 (11.2 microm) is more transparent than other
      channels. For cirrus clouds only, when the optical thickness of cirrus tau(c) is
      <0.10, channel 8 is still more transparent, while, with tau(c) increasing from
      0.2 to between 4 and 8, channel 12 (4 microm) becomes the most transparent. When
      tau(c) >/= 8, the transparency of channel 12 decreases and those of other
      channels increase. For a very large r, the transparency of VAS channels will
      become almost equal. In addition, the IR absorption emittance of cirrus and the
      brightness temperatures also have sensitivities to different cloud optical
      thicknesses. The general retrieval equation for the determinations of SST, which
      is suitable for the clear air model as well as for the cirrus cloud atmospheres
      (with our definition of cirrus), is obtained through a combination of channels
      12, 8, 6 (4.5 microm), and 5 (13.3 microm).The retrieval error is <1.0 K. The
      error analyses indicate that the clear air retrieval equations should not be used
      for SST determination in cirrus conditions.

PMID- 20700316
TI  - Trans-spectral absorption and scattering of electromagnetic radiation by diesel
      soot.
AB  - The mass density normalized absorption and total scattering coefficients have
      been measured using in situ techniques at selected wavelengths from the visible
      to approximately 1 cm for soot generated by the open combustion of diesel fuel.
      Particle morphologies are complex although similar to those of soots of other
      hydrocarbons and methods of generation. An ellipsoidal model has been applied as
      an approximation to the often multiconnected, chainlike aerosol and then compared
      with the measured results. The experimental results show an approximate (lambda)(
      1) dependence over more than five decades of wavelength data. There is only
      general agreement with the simplified calculations in this feature as well as in
      the magnitude.

PMID- 20700317
TI  - Empirical formula for optical absorption by fractal aerosol agglomerates.
AB  - An empirical formula for calculating the optical absorption of fractal aerosol
      agglomerates over a broad frequency range is derived based on extensive
      calculations made on five smoke agglomerates having a widely varying number of
      particles ranging from 12 to 372 and an almost constant fractal dimension in the
      1.7-1.9 range. The expansion coefficients in the empirical formula were
      determined by least-squares curve fiting of numerical data obtained using the
      volume integral equation formulation (VIEF).(1) The formula satisfies the
      frequency dependence of the absorption at lower frequencies and up to the
      resonance frequency of the agglomerate. Expressions for the resonance frequency
      (f(0)), as well as the constant coefficients in the empiricial formula, are
      derived in terms of the structural dimensions, number and size of the primary
      particles, and the complex permittivity of the aerosol agglomerate. Numerical
      results obtained from the empirical formula are generally in good agreement with
      those calculated by the VIEF for soot particles with a magnitude of complex
      permittivity |epsilon*| in the 1-7 range. The average error in the absorption
      calculation is <5%. The formula thus provides a simple and inexpensive method for
      calculating the optical absorption of aerosol agglomerates, which otherwise
      require complicated and expensive methods of calculation. This formula also
      facilitates the implementation of the accurate VIEF results in large climate
      codes such as the general circulation model.

PMID- 20700318
TI  - Backscattersonde: a new instrument for atmospheric aerosol research.
AB  - A relatively simple balloonborne device for measuring the local aerosol
      backscatter at multiple wavelengths has been developed and field tested. The
      instrument produces detailed profiles which are inherently similar to those
      generated from lidar soundings. It is also sensitive, being able to measure the
      20-km stratospheric aerosol background layer with a signal-to-noise ratio of
      approximately 100:1. An important feature of this device is its ability to be
      calibrated in an absolute sense. Theoretical considerations show that the
      measurements can be accurately converted to aerosol mass loading in the
      stratosphere for conditions ranging from background to heavy volcanic influence.
      The instrument is not expected to replace other observational techniques; rather
      it provides highly complementary information as well as furnishes a cost
      effective alternative to measurement systems available to only a few scientists.

PMID- 20700319
TI  - Multiple vs single scattering: assessment of magnitudes.
AB  - All orders of scattering are analyzed for two artificial canopies. The SHL canopy
      consists of Small Horizontal Leaves that are much smaller than the leaf-to-leaf
      spacing. The IHL canopy consists of Infinite Horizontal Layers, where each leaf
      is of infinite extent (a horizontal plane). Hemispheric leaf reflectances and
      transmittances independent of the direction of illumination lead to exact
      solutions for these models. Sunlight that penetrates to a given leaf area index
      level is much stronger in an SHL canopy than that in IHL; but the difference
      becomes muted when leaf transmittance is large. Multiple scattering enhances the
      hemispheric canopy reflectance more strongly in SHL than it does in IHL. The
      enhancement depends linearly on leaf transmittance in SHL and on the
      transmittance squared in IHL. Comparison with measured reflectances ndicates that
      IHL model grossly underestimates multiple scattering in soybean canopies.

PMID- 20700320
TI  - Inadequate heating of fused silica components during the coating process.
AB  - The customary method of heating fused silica optical components during the
      coating process is shown to result in low temperature and poor coating
      performance.

PMID- 20700321
TI  - Possibilities for projection x-ray lithography using holographic optical
      elements.
AB  - The use of a single flat grazing incidence reflector on which a computer
      generated hologram has been written is proposed for projection x-ray lithography.

PMID- 20700322
TI  - Temperature dependence of optical constants of MoS(2) for pyrooptical devices.
AB  - The temperature sensitivity of the reflectance of MoS(2) under small temperature
      modulations has been investigated.It is feasible to detect temperature changes of
      10(-2) degrees C by monitoring the reflectance, and thus MoS(2) is a potential
      candidate material for the pyrooptical sensors.

PMID- 20700323
TI  - ABCD matrix for weakly apertured Gaussian beams in the far field.
AB  - When a Gaussian beam is weakly diffracted by a circular aperture it can be
      approximated by another Gaussian beam with slightly different properties in the
      far field. In this Technical Note, using the relationship between these two
      Gaussian beams, before and after the aperture, an ABCD matrix is defined for
      cascaded laser systems.

PMID- 20700324
TI  - ABCD matrix for apertured spherical waves.
AB  - An ABCD matrix for describing the hard aperture under a large Fresnel number is
      defined in this Technical Note based on Li and Wolf's formula. It is useful for
      analyzing focal shifts of complicated optical systems with hard apertures.

PMID- 20700325
TI  - Two-dimensional reflection imaging scanner isolates illumination and collection
      paths.
AB  - A two-dimensional confocal imaging scanner uses galvanometer-controlled mirrors
      which are silvered on both sides to separate illumination and collectiono pticalp
      aths.

PMID- 20700326
TI  - Annulling parasitic fringes in real time holographic interferometry: a new
      method.
AB  - A method for annulling parasitic fringes in real time holographicin terferometrya
      nd its theoreticalj ustification is presented. The main advantage relates to
      cancellation of nondesired object motions or deformations with experimental
      simplicity.

PMID- 20700327
TI  - Design considerations for the rotation of a plane premirror of a monochromator
      for reflecting synchrotron radiation onto the same spot of the dispersing grating
      of the XUV beamline.
AB  - The kinematic concept of employing a plane premirror rotated around an axis
      outside its surface to reflect the beam onto the same spot on the grating for
      three angular positions is formulated algebraically. Exact analytic solutions are
      found for determining the positions of the axis of rotation, the radius of the
      circle of rotation, and the central fixed spot on the grating in terms of the
      three angles and the height 2b of the grating above the incident beam. Typical
      numerical calculations are presented and discussed. It is generally observed that
      deviation of the reflected beam from the fixed spot is barely a few microns for b
      in centimeters.

PMID- 20700328
TI  - Diffraction field of a circularly symmetric beam through a sequence of apertures.
AB  - A method to compute the diffraction field of a circularly symmetric laser beam
      through a sequence of circular apertures is discussed. An explicit expression of
      the field is given as the linear combination of a set of values of the input
      beam. Comparisons with numerical integration and experimental data available in
      the literature show its accuracy even in the Fresnel region where approximate
      methods such as the beam mode expansion are less accurate.

PMID- 20700329
TI  - Methylene blue sensitized dichromated gelatin holograms: a new electron donor for
      their improved photosensitivity.
AB  - Tetramethylguanidine (TMG) used as the electron donor in conjunction with
      methylene blue sensitized dichromated gelatin (MBDCG) can produce bright
      reflection holograms recorded at 633 nm at an exposure level of 50 mJ/cm(2). Thus
      DCG hologram recording and some independence from suppliers of proprietary
      holographic recording materials is now open to all those with low power He-Ne
      lasers. The high alkalinity of the system allows the unexposed coated material to
      have an effective lifetime at room temperature of weeks rather than days. Its low
      dichromate content has an environmental advantage over the usual DCG
      formulations. Replacement of methylene blue by eosin can produce similar
      photosensitivity to 514 nm. The superiority of TMG over previously reported
      electron donors used with MBDCG is discussed.

PMID- 20700330
TI  - Real-time holographic phase organization technique to obtain customized
      contouring of diffuse surfaces.
AB  - We report on the development of a holographic technique which allows one to
      obtain real time holographic fringes that reveal the whole field contour map of
      an arbitrary shaped object. The method enables one to generate sensitivities
      compatible with the relief variations of objects of broadly varying depths. This
      is achieved by supplying enough 3-D modulation capacity to the system to develop
      the desired sensitivity. The intersection planes can be pivoted to provide for an
      oblique slicing of the model. We describe the basic optical configuration and
      discuss the system parameters. Experimental results are presented to illustrate
      the effectiveness of the method.

PMID- 20700331
TI  - Factorial optimization of bleach constituents for silver halide holograms.
AB  - A factorial design approach to optimizing rehalogenating bleaches for silver
      halide holograms is presented. An advantage of this technique is that it allows
      simultaneous improvement in a number of hologram performance characteristics as a
      function of several input parameters. Interactive effects of combinations of
      input parameters can also be examined. A specific experiment is described in
      which diffraction efficiency, average light loss, thickness change, and noise
      grating efficiency are optimized as a function rehalogenating agent, oxiding
      agent, and acid concentrations of a rehalogenating bleach. Results for both Agfa
      8E75HD and Ilford SP673 films are presented.

PMID- 20700332
TI  - Three-illumination-beam phase-shifted holographic interferometry study of
      thermally induced displacements on a printed wiring board.
AB  - Spatially resolved measurement of thermally induced surface displacements of
      printed wiring boards using phase-shifted holographic interferometry is
      discussed. Three separate holograms with three linearly independent illumination
      beams were recorded. The interferograms were viewed in real time from a fixed
      detector location, and phase maps corresponding to each illumination direction
      were generated with the phase-shifting interferometer. The phase maps are then
      used to compute the displacements on a point by point basis. The measurement
      accuracy is estimated to be +/-0.004 microm out-of-plane and +/-0.02 microm in
      plane over a temperature range of 40 degrees C. The system was tested on a
      through hole in a printed wiring board; the results of this test are discussed.
      Phase computation and unwrapping, data reduCtion, experimental geometry, surface
      preparation, and displacement computation are discussed.

PMID- 20700333
TI  - Algorithm for computer tracing of interference fringes.
AB  - An algorithm for automatic tracing of fringes from a digitized interferogram is
      proposed. The main feature of this method is that fringe centers are traced by a
      predictor-corrector scheme, where knowledge of the approximate fringe normal and
      tangent at the current point on a fringe is used to guess at a trial location for
      the next point. A search along the fringe normal at the new trial location then
      yields the exact next point on the fringe.

PMID- 20700334
TI  - Multimode fiber interferometry with and without phase conjugation.
AB  - It is generally assumed that fiber interferometers must be constructed from
      single-mode fibers. An alternative is to employ phase conjugation mirrors on the
      arms of a multimode fiber interferometer so that the spatial scrambling of modes
      is reversed, and good fringe contrast is maintained. When several interferometers
      all share the same self-conjugating BaTiO(3) crystal, however, the results show
      crosstalk between the separate fibers ranging from negligible to prohibitively
      large depending on the precise spatial configuration within the conjugator. A
      model accounting for these results is proposed. In addition it was observed in
      control experiments with conventional Mach-Zehnder configurations that good data
      could be obtained despite reduced contrast with both graded and step index
      multimode fibers.

PMID- 20700335
TI  - Three-channel phase stepped system for moire interferometry.
AB  - A use of the multichannel phase stepped interferometry approach to automated
      fringe pattern analysis in moire interferometry is described. Polarization optics
      is used to implement the appropriate phase shifts in each channel. The channels
      are created by inserting a diffraction grating at the output of the
      interferometer. It is possible to work at one frame rate. This system enables
      studies in unstable environmental conditions and studies of time dependent
      events.

PMID- 20700336
TI  - Image processing algorithms for the analysis of phase-shifted speckle
      interference patterns.
AB  - A sequence of image processing algorithms for the analysis of interference
      patterns generated by a phaseshifting speckle interferometer is discussed. The
      goal is the accurate determination of displacement and strain components at the
      surface of an object. The phase change related to the displacement is accurately
      calculated from eight digitized interference patterns using a phase-shifting
      algorithm. Digital image processing algorithms have been developed for phase
      unwrapping, phase restoration, and phase fitting. During the processing steps a
      binary mask is used to solve the problem of invalid areas. Experimental results
      for the strain components at the surface of a simple object demonstrate a
      repeatability of 0.3-microstrain rms.

PMID- 20700337
TI  - Position sensing of a grating mark by heterodyne detection using a Zeeman laser.
AB  - A way to detect with high resolution the position of a wafer and a mask is
      proposed and evaluated. In this method, a grating mark on a wafer or a mask is
      detected by heterodyne interference using a He-Ne Zeeman laser. Experiments show
      that the position of a wafer or a mask could be detected with a resolution of
      approximately 0.01 microm.

PMID- 20700338
TI  - Precision displacement measurement by active laser heterodyne interferometry.
AB  - We demonstrate an active laser heterodyne interferometer which can automatically
      compensate environmental disturbances and is capable of precision displacement
      measurement. Two Zeeman He-Ne lasers were employed. Laser II was used as the
      light source to stabilize the interferometer by using a piezomirror in a feedback
      loop. The hetereodyne signal of the two lasers was used to directly calibrate
      mirror displacement, with the wavelength of laser I tuned to compensate change in
      the interference signal due to displacement only. Separation of the contributions
      to the interference signal from displacement and external disturbances was
      accomplished by using polarization optics. This interferometer was used to
      measure the hysteresis of a piezoelectric transducer (PZT) over a dynamic range
      of 0.5 microm with a resolution of +/-0.8 nm.

PMID- 20700339
TI  - Possible high absorptance and low emittance selective surface for high
      temperature solar thermal collectors.
AB  - Optical reflectivity measurements show that the reflectivity of Ge is
      dramatically reduced in the wavelength 0.3-1.4-microm range after high dose
      oxygen ion implantation. To explain such greatly reduced reflectivity, a model
      has been developed for the reflectivity of high dose oxygen implanted germanium.
      Our experimentally measured and calculated reflectivities show that, for a
      layered structure consisting of a Ge and GeO(2) mixture on Ge on GeO(2) on a Cu
      substrate, a low reflectivity of 0-10% in the solar spectrum is obtained,
      together with a high reflectivity approximately 100% in the 1.7-25-microm
      wavelength range. This is close to that of an ideal selective surface for solar
      energy thermal collectors operating at high temperatures from 300 to 500 degrees
      C.

PMID- 20700340
TI  - Modulation transfer function cascade model for a sampled IR imaging system.
AB  - The performance of the infrared scanning radiometer (IRSR) is strongly stressed
      in convective heat transfer applications where high spatial frequencies in the
      signal that describes the thermal image are present. The need to characterize
      more deeply the system spatial resolution has led to the formulation of a cascade
      model for the evaluation of the actual modulation transfer function of a sampled
      IR imaging system. The model can yield both the aliasing band and the averaged
      modulation response for a general sampling subsystem. For a line scan imaging
      system, which is the case of a typical IRSR, a rule of thumb that states whether
      the combined sampling-imaging system is either imaging-dependent or sampling
      dependent is proposed. The model is tested by comparing it with other noncascade
      models as well as by ad hoc measurements performed on a commercial digitized
      IRSR.

PMID- 20700341
TI  - Analytical electrical model for a Si liquid crystal light valve.
AB  - An approximate analytical model has been developed which allows the voltage
      characteristics of the liquid crystal layer of a silicon liquid crystal light
      valve to be determined once the photocurrent level and device parameters have
      been specified. This model significantly decreases the computation time compared
      to current numerical techniques.

PMID- 20700342
TI  - Projection moire fringe pattern prediction using the optical transfer function.
AB  - Theoretical treatment of the projection moire fringe pattern (PMFP) based on the
      optical transfer function is presented. Contrast is used as a criterion for the
      quality of the PMFP. In the case of a diffraction-limited system and variable
      focusing error, theoretical results are compared to measured values.

PMID- 20700343
TI  - Automated high precision variable aperture for spectrophotometer linearity
      testing.
AB  - A new automated linearity tester with a single variable aperture has been
      designed and built. It uses piezoelectric motors to define precisely the
      apertures required for application of the double aperture method of light
      addition. This design avoids many of the inherent shortcomings of two fixed
      physically separated apertures, such as interference and coherence between two
      separated beams and the need for an averaging sphere to compensate for beam
      noncoincidence at the photoreceiver. It also permits the assessment of system
      nonlinearity for arbitrary flux levels over an approximately 70:1 dynamic range
      without the use of a supplementary means of optical attenuation. The tester was
      specifically designed for use with the National Research Council of Canada
      Reference spectrophotometer, but it can be adapted for use with any instrument
      with a large stable measurement beam. The paper discusses the correct placement
      and operation of this device. The performance, as evaluated by nonlinearity
      measurements of a known highly linear silicon photodiode, shows a reliability of
      <1-3 parts in 10(4) over a 3400:1 dynamic range at a 97% confidence level.
      Several applications of this linearity tester to both photomultipliers and
      photodiodes are described. Transmittance results for several reference materials
      using these linearity corrected photodetectors are compared and show a typical
      agreement of better than 0.025% of the value.

PMID- 20700344
TI  - Possibility of lifetime measurement in a flowing medium with phase fluorometry.
AB  - The possibility of lifetime measurement in a flowing medium with phase
      fluorometry is investigated theoretically. A 3-D time dependent partial
      differential equation of the number density of atoms (or molecules) in the upper
      level of the fluorescence transition is solved analytically, taking flow,
      diffusion, optical excitation, decay, Doppler shift, and thickness of the
      excitation light sheet into account. An analytical expression of the intensity of
      the fluorescence signal in the flowing medium is deduced. Conditions are given,
      in which the principle of lifetime measurement with phase fluorometry in the
      static sample cell can be used in a flowing medium.

PMID- 20700345
TI  - Rangefinder based on intensity gradient measurement.
AB  - An algorithm is derived which enables the range of an object to be measured by
      passive optical means. It is shown that the distance of an object from an
      observation point is given by the ratio of the angular intensity gradient to the
      translational intensity gradient of a segment of the object's intensity profile,
      as seen from the observation point. The algorithm is implemented by two rows of
      photodetectors with angular sensitivity functions g(alpha) and g'(alpha),
      positioned in pairs along a baseline, at equal distances and with parallel
      optical axes. Weighted sums of the outputs are formed for each row, the weights
      being defined by a pair of functions of position on the baseline h'(T) and h(T).
      The ratio of the two sums is proportional to distance, independent of background
      intensity and contrast. A device based on this principle, using simple analog
      electronics and commercially available photodetectors, is described, and its
      performance is evaluated.

PMID- 20700346
TI  - Glass flake reinforced composites as optical materials.
AB  - The optical properties of glass flake composites are investigated by measuring
      the transmission of collections of flakes in index matched oils over a wide
      temperature range. For large refractive index differences between glass and
      matrix, the transmission is periodic with temperature and is interpreted as
      Fresnel diffraction from a transparent edge. For small refractive index
      differences, the Rayleigh-Gans (RG) light scattering theory for thin circular
      disks is used to correlate the data. A model is developed for predicting the
      flake size and concentration necessary in a particular polymer matrix for the
      resulting composite to meet given temperature dependent haze requirements.

PMID- 20700347
TI  - Measurement of the index of refraction of the plastic Phenoxy PKFE.
AB  - The index of refraction, n of Phenoxy PKFE, a light yellow plastic produced by
      Union Carbide, is measured at lambda = 588 nm (n(D)), lambda = 656 nm (n(C)), and
      lambda = 486 nm (n(F)). These values are of interest because they must be known
      to determine the optical characteristics of a Phenoxy PKFE lens over the visible
      spectrum. Lenses made of Phenoxy PKFE have an important advantage over lenses
      made of other plastics. Phenoxy PKFE is chemically resistant to many epoxy glues
      commonly used to form airtight bonds in hermetically sealed chambers.

PMID- 20700348
TI  - Fiber optic interferometer for testing conic section surfaces.
AB  - A null test method for testing aspheric optical surfaces based on geometric
      considerations of conic sections is presented. The basic principles have been
      investigated experimentally by designing and building a modified Mach-Zehnder
      interferometer. By using optical fibers the inconvenience of alignment has partly
      been overcome. Phase shifting has been implemented and the measurements are
      performed with the help of a microcomputer. The performance of the interferometer
      has been investigated by testing an elliptical toroid mirror. Further improvement
      of the test procedure by Zernike polynomial decomposition is discussed and
      performed. Finally, an even more compact conic section interferometer is
      proposed.

PMID- 20700349
TI  - Characteristic curves for photographic emulsions from nonlinear fitting: a study
      of statistical and model error.
AB  - The intensity calibration of photographic emulsions is examined from the
      standpoint of nonlinear leastsquares fits to analytic expressions. A simple but
      widely neglected expression for computing the propagated statistical error is
      used to examine the error in the relative exposure as determined from the fitted
      calibration function. The statistical error is also compared with the dependence
      on the choice of fit function, or model error. In the present applications, which
      replicate those obtainable routinely in emission spectroscopy, the relative
      intensity is obtainable to better than 10% over a 2-order-of-magnitude change in
      intensity.

PMID- 20700350
TI  - Coherency matrix polarization measurements: application to magnetooptic garnet
      films.
AB  - A method of completely determining the polarization of light is described. An
      algorithm that allows a fast numerical evaluation of the coherency matrix based
      on the results of four nonequivalent polarization measurements is presented. The
      method has been applied to determine the degree of polarization, ellipticity, and
      orientation of the major axis of light transmitted through a magnetooptic thin
      film on a garnet substrate as a function of magnetic field. Representative
      results are given.

PMID- 20700351
TI  - Optical performance evaluation of a circular cylindrical solar concentrator using
      different absorber shapes.
AB  - The concentration characteristics of a seasonally adjusted circular cylindrical
      solar concentrator arr studied for four different absorber configurations: flat
      horizontal, flat vertical, tubular, and defocused tubular absorber with a
      vertical fin. The effect of normally distributed mirror surface slope errors on
      the concentration characteristics of the concentrator is also investigated.

PMID- 20700352
TI  - Multilayer reflecting x-ray optical systems: chromatic vignetting by narrow
      reflection bands.
AB  - A multilayer mirror reflecting optical system of unlimited numerical aperture can
      be made to focus one point onto another. On an axially symmetric system this is
      done by radially varying the multilayer Bragg spacing on each mirror. If the
      wavelength is less than approximately 75 A, the number of layer pairs required
      for optimal reflectance rises above 40. The resulting reflection bandwidth
      Deltalambda/lambda will be <1/40, over which the optical phase changes by
      approximately 180 degrees . With such a narrow band, correct variation of layer
      spacing for an axial image point would seriously reduce the reflectance in some
      regions, and the phase coherence across the mirror, for source and image points
      within a rather small radius off-axis. This problem, which might be called
      chromatic vignetting, is not restricted to axially symmetric systems and should
      be investigated for any multilayer reflecting optical system. We find that for
      moderately large images with mirrors of moderate size it is better to use uniform
      multilayer spacing across any one mirror than to correct for one image point.
      This will limit the numerical aperture and resolution but will result in uniform
      resolution and intensity over the entire image. The increasing number of layers
      required for x-rays of shorter wavelengths actually results in a decrease in
      resolution with wavelengths shorter than approximately 75 A for such systems.

PMID- 20700353
TI  - Design criteria for band rejection filters made from multilayers of dielectric
      and ultrathin metal films.
AB  - Narrowband rejection filters can be constructed from multilayers of dielectric
      and ultrathin metal films operating in the anomalous skin effect region
      constrained by the optical size effect. The wavelength of the main reflecting
      spectrum is wholly determined by the dielectric thickness, and the bandwidth can
      be reduced by increasing the total number of layers and selecting the dielectric
      film with high refractive index while diminishing the thickness of the metal
      film.

PMID- 20700354
TI  - X-ray optics. 2: A technique for high resolution spectroscopy.
AB  - A novel combination of optical elements and properties is combined to achieve
      high spectral resolution using grazing incidence optics of modest quality. We
      show through analysis and ray tracing of examples that using radial groove
      gratings at high blaze angles in the manner of an echelle spectrograph can
      provide high spectral resolution. We compare this arrangement to the conventional
      in-plane designs and show the off-plane to be superior in nearly every respect.
      Cross dispersion can be provided by the energy resolution of a CCD detector.
      Then, we show how additional resolution can be squeezed from the system by
      strategic placement of gratings to take advantage of the azimuthal response of a
      Wolter x-ray optic. With a telescope that has only 30-sec of arc imaging we are
      able to support resolution lambda/deltalambda of 3000, while a conventional
      design at the same graze angle supports resolution of only 200.

PMID- 20700355
TI  - Applied optics of optics and opticists.

PMID- 20700356
TI  - Experiments on nonlinear joint transform correlator using an optically addressed
      spatial light modulator in the Fourier plane.
AB  - Correlation experiments for the images used in the proposed setup indicate that
      nonlinear compression of the joint power spectrum may be necessary to produce
      good correlation performance and a peak-to-sidelobe ratio of larger than unity.

PMID- 20700357
TI  - Nonlinearly transformed baseband filters for optical pattern recognition.
AB  - The real part of the linear matched filter is nonlinearly transformed. Various
      types of filter including binary phase-only filters are produced by varying the
      severity of the nonlinearity.

PMID- 20700358
TI  - Butterfly interconnection implementation for an n-bit parallel ripple carry full
      adder.
AB  - Free-space optical interconnections are important both in massive digital optical
      computing and in communication systems. The optical butterfly interconnection has
      many advantages over other interconnections in implementing various basic logic
      functions such as addition, subtraction, multiplication. This paper starts with
      the conventional Karnaugh maps and Boolean algebra to implement a parallel n-bit
      ripple carry full adder by the use of multilayer butterfly interconnection
      networks. Then we describe in detail the design and architecture of the full
      adder and provide accurate interconnection networks and the structures or
      patterns of key devices such as the masks to implement AND and OR operations in
      this calculation. Finally, we discuss development of the interconnection in
      implementing logic operations.

PMID- 20700359
TI  - Use of electron trapping materials in optical signal processing. 3: Modifiable
      Hopfield type neural networks.
AB  - Novel electron trapping materials are capable of performing optical formation of
      an interconnection matrix based on the Hopfield prescribed learning rule. The
      matrix is further modifiable when a memory is changed or added. An association is
      performed using the optically formed matrix. In addition, the construction of
      single liquid crystal display XOR and XNOR gates for the matrix formulation is
      described. The XOR operation of an electroluminescent lamp is demonstrated.

PMID- 20700360
TI  - Third-order aberrations for holograms and holographic lenses recorded on quadrics
      of revolution.
AB  - Third-order aberrations of holograms recorded on the quadrics of revolution for
      small fields of view have been investigated. The possibilities of compensating
      some aberrations for lenses recorded on the quadrics of revolution have been
      studied in more detail. This paper shows that the most simple aberration
      coefficients for holograms recorded on quadrics of revolution are for spherical
      holograms.

PMID- 20700361
TI  - Three-dimensional confocal imaging of objects embedded within thick diffusing
      media.
AB  - Confocal scanning methods are modified to allow 3-D imaging of objects embedded
      within thick diffusing media. A method called exfoliative deconvolution is used
      to sharpen a volume image in which the blur is depth variant. Experimental
      results are presented.

PMID- 20700362
TI  - Coherent array optical imaging.
AB  - This paper describes a technique that allows a severely distorted coherent
      optical array receiver to produce images comparable to conventional monolithic
      imaging systems. The technique is based on using a phase synchronizing point
      source as a reference to eliminate phase errors in the array. Once phase
      corrected, the individual elements in the array can be coherently combined to
      yield a resolution equal to the overall size of the array, and if Doppler
      information is available, separation of targets within the diffraction limited
      spot size of the array is possible. Experimental verification of concepts
      developed within this paper is presented for array receivers operating at 633 and
      514 nm.

PMID- 20700363
TI  - Reconstruction of an axisymmetric image from its blurred and noisy projection.
AB  - The 3-D velocity distribution of ionized photofragments resulting from the
      dissociation of methyl iodide is recovered by digitally deblurring and Abel
      inverting a single measured 2-D projection. The reconstructed distribution
      reveals two rings which are the dissociation channels corresponding to ground
      state and excited state iodine. A factor of 1.6 in resolution improvement of the
      channels is achieved by deconvolving the 2-D projection using a line-by-line
      implementation of Kawata's reblur algorithm. This technique guarantees noise
      smoothed projections for the notoriously sensitive Abel inversion procedure,
      which in this paper is implemented using discrete Fourier and Hankel transforms.

PMID- 20700364
TI  - Rotationally invariant Fresnel lens-encoded circular harmonic binary phase-only
      filters.
AB  - Binary phase-only circular harmonic filters show an angular dependence on the
      rotational orientation of the input object, which can be removed by encoding a
      Fresnel lens onto the filter. Theoretical and experimental results are presented
      using these filters written onto the magnetooptic spatial light modulator.

PMID- 20700365
TI  - Design and performance optimization of fiber optic adaptive filters.
AB  - There is a great need for easy-to-fabricate and versatile fiber optic signal
      processing systems in which optical fibers are used for the delay and storage of
      wideband guided lightwave signals. We describe the design of the least-mean
      square algorithm-based fiber optic adaptive filters for processing guided
      lightwave signals in real time. Fiber optic adaptive filters can learn to change
      their parameters or to process a set of characteristics of the input signal. In
      our realization we employ as few electronic devices as possible and use optical
      computation to utilize the advantages of optics in the processing speed,
      parallelism, and interconnection. Many schemes for optical adaptive filtering of
      electronic signals are available in the literature. The new optical adaptive
      filters described in this paper are for optical processing of guided lightwave
      signals, not electronic signals. We analyzed the convergence or learning
      characteristics of the adaptive filtering process as a function of the filter
      parameters and the fiber optic hardware errors. From this analysis we found that
      the effects of the optical round-off errors and noise can be reduced, and the
      learning speed can be comparatively increased in our design through an optimal
      selection of the filter parameters. A general knowledge of the fiber optic
      hardware, the statistics of the lightwave signal, and the desired goal of the
      adaptive processing are enough for this optimum selection of the parameters.
      Detailed computer simulations validate the theoretical results of performance
      optimization.

PMID- 20700366
TI  - Two-dimensional particle displacement tracking in particle imaging velocimetry.
AB  - A new particle imaging velocimetry data acquisition and analysis system, which is
      an order of magnitude faster than any previously proposed system, has been
      constructed and tested. The new particle displacement tracking (PDT) system is an
      all electronic technique employing a video camera and a large memory buffer frame
      grabber board. Using a simple encoding scheme, a time sequence of single exposure
      images is time coded into a single image and then processed to track particle
      displacements and determine 2-D velocity vectors. Use of the PDT technique in a
      counterrotating vortex flow produced over 1100 velocity vectors in 110 s when
      processed on an 80386 PC.

PMID- 20700367
TI  - Improved photorefractive time response using a cylindrical lens.
AB  - Experimental observations are reported which demonstrate that the response time
      for beam fanning, self-pumped phase conjugation, and double phase conjugation can
      be shortened by more than an order of magnitude without a significant reduction
      in coupling strength by using a cyclindrical lens to focus incident laser light
      into a photorefractive crystal. These results are compared with those obtained
      using a spherical lens where a reduction in the photorefractive response time is
      accompanied by a corresponding reduction in coupling strength. It is shown that
      the fidelity of a phase conjugate beam is not degraded when cylindrical optics
      are used.

PMID- 20700368
TI  - An association between BPDE-like DNA adduct levels and CYP1A1 and GSTM1
      polymorphisma in pterygium.
AB  - PURPOSE: Benzo[a]pyrene 7,8-diol 9,10-epoxide (BPDE), an ultimate metabolite of
      benzo[a]pyrene, attacks deoxyguanosine to form a BPDE-N2-dG adduct resulting in
      p53 mutations. Both cytochrome P4501A1 (CYP1A1) and glutathione S-transferase M1
      (GSTM1) have been demonstrated to be involved in the metabolism of polycyclic
      aromatic hydrocarbons. The relationship between BPDE-like DNA adduct levels and
      CYP1A1 and GSTM1 gene polymorphisms in pterygium is not clear. Therefore, BPDE
      like DNA adducts and CYP1A1 and GSTM1 polymorphisms were detected in this study
      to provide more molecular evidence to understand the cause of BPDE-like DNA
      adduct formation in pterygium. METHODS: In this study, immunohistochemical
      staining using a polyclonal antibody on BPDE-like DNA adducts was performed on
      103 pterygial specimens. For the analysis of CYP1A1 and GSTM1 polymorphisms, DNA
      samples were extracted from epithelial cells and then subjected to restriction
      fragment length polymorphism (RFLP) and polymerase chain reaction (PCR) for the
      determination of mutation and genotype of CYP1A1 and GSTM1. RESULTS: BPDE-like
      DNA adducts were detected in 33.0% (34/103) of the pterygium samples. The
      differences in DNA adduct levels were associated with the genetic polymorphisms
      of CYP1A1 but not GSTM1. Additionally, the risk of BPDE-like DNA adduct formation
      for patients with CYP1A1 m1/m2 (C/T) andm2/m2 (T/T) was 9.675 fold higher than
      that of patients with CYP1A1 m1/m1 (C/C) types (p=0.001, 95% Confidence Interval
      2.451-38.185). CONCLUSIONS: Our data provide evidence that the BPDE-like DNA
      adduct formation in pterygium samples was associated with CYP1A1 polymorphisms.

PMID- 20700369
TI  - Characterization and functional expression of the natriuretic peptide system in
      human lens epithelial cells.
AB  - PURPOSE: The family of natriuretic peptides (NPs); atrial natriuretic peptide
      (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) as
      well as three associated receptors (NPRs); natriuretic peptide receptor A (NPR
      A), natriuretic peptide receptor B (NPR-B), and natriuretic peptide receptor C
      (NPR-C) has never been documented in human lens epithelial cells. The study
      described herein was designed to demonstrate both expression and functionality of
      components of the natriuretic peptides and natriuretic peptide receptors in the
      human lens epithelial cell line, HLE-B3 and in normal human lens epithelial cell
      cultures (nHLE). METHODS: Reverse transcriptase-polymerase chain reaction (RT
      PCR) along with confirmation by DNA sequencing and real-time quantitative RT-PCR
      was used to identify and demonstrate expression of mRNA for the natriuretic
      peptide family. Authentication of protein expression of the natriuretic peptide
      receptors was determined by using formaldehyde-fixed, Saponin-permeabilized cells
      (HLE-B3) or methanol:acetone-fixed and permeabilized cells (nHLE) using
      conventional immunofluorescence techniques. Enzyme-linked immunosorbent assay was
      used to determine cyclic GMP (cGMP) activity as stimulated by exogenous addition
      of natriuretic peptides. RESULTS: Using RT-PCR with confirmation by DNA
      sequencing and real-time quantitative RT-PCR, HLE-B3 cells were shown to express
      mRNA for ANP, BNP, and CNP along with their associated receptors. Conventional
      immunofluorescence on the permeabilized cells confirmed positive diffuse staining
      indicating the presence of the three natriuretic peptide receptors in both HLE-B3
      and nHLE cells. All three natriuretic peptides educe a cGMP response in the rank
      order CNP>>ANP approximately BNP indicating that the natriuretic peptide family
      is functional in HLE-B3 cells. CONCLUSIONS: The data indicates that ANP, BNP, and
      CNP and natriuretic peptide receptor transcripts are expressed and are functional
      in human lens epithelial cells. The cellular expression of NPs and NPRs, as well
      as the demonstration that all three NPs activate guanylyl cyclase suggests a
      potential role in maintaining lens epithelial cell homeostasis.

PMID- 20700370
TI  - Mexican American Parents' Involvement in Adolescents' Peer Relationships:
      Exploring the Role of Culture and Adolescents' Peer Experiences.
AB  - This study examined the nature and correlates of Mexican American mothers' and
      fathers' involvement in adolescents' peer relationships along four dimensions:
      support, restriction, knowledge, and time spent with adolescents and peers.
      Mexican American adolescents and their parents in 220 families described their
      family relationships, cultural orientations/values, and experiences with
      adolescents' peers in home interviews. In addition, time-use data were collected
      during a series of seven phone calls to measure parents' time spent with
      adolescents and peers and parents' knowledge of adolescents' daily experiences
      with peers. Multi-level models revealed connections between parents' involvement
      in adolescents' peer relationships and both parents' Mexican and Anglo
      orientations and familism values and adolescents' peer experiences (e.g., deviant
      peer affiliations, friends' ethnic orientation). Findings further revealed some
      evidence that parent and adolescent gender moderated the patterns, with mothers'
      (but not fathers') restrictions on peer relationships being associated with
      adolescents' deviant peer affiliations and parents placing greater restrictions
      on daughters' than on sons' peer relationships when they had more frequent
      deviant peer affiliations.

PMID- 20700371
TI  - The rate of growth in scientific publication and the decline in coverage provided
      by Science Citation Index.
AB  - The growth rate of scientific publication has been studied from 1907 to 2007
      using available data from a number of literature databases, including Science
      Citation Index (SCI) and Social Sciences Citation Index (SSCI). Traditional
      scientific publishing, that is publication in peer-reviewed journals, is still
      increasing although there are big differences between fields. There are no
      indications that the growth rate has decreased in the last 50 years. At the same
      time publication using new channels, for example conference proceedings, open
      archives and home pages, is growing fast. The growth rate for SCI up to 2007 is
      smaller than for comparable databases. This means that SCI was covering a
      decreasing part of the traditional scientific literature. There are also clear
      indications that the coverage by SCI is especially low in some of the scientific
      areas with the highest growth rate, including computer science and engineering
      sciences. The role of conference proceedings, open access archives and
      publications published on the net is increasing, especially in scientific fields
      with high growth rates, but this has only partially been reflected in the
      databases. The new publication channels challenge the use of the big databases in
      measurements of scientific productivity or output and of the growth rate of
      science. Because of the declining coverage and this challenge it is problematic
      that SCI has been used and is used as the dominant source for science indicators
      based on publication and citation numbers. The limited data available for social
      sciences show that the growth rate in SSCI was remarkably low and indicate that
      the coverage by SSCI was declining over time. National Science Indicators from
      Thomson Reuters is based solely on SCI, SSCI and Arts and Humanities Citation
      Index (AHCI). Therefore the declining coverage of the citation databases
      problematizes the use of this source.

PMID- 20700372
TI  - Harmonic publication and citation counting: sharing authorship credit equitably -
      not equally, geometrically or arithmetically.
AB  - Bibliometric counting methods need to be validated against perceived notions of
      authorship credit allocation, and standardized by rejecting methods with poor fit
      or questionable ethical implications. Harmonic counting meets these concerns by
      exhibiting a robust fit to previously published empirical data from medicine,
      psychology and chemistry, and by complying with three basic ethical criteria for
      the equitable sharing of authorship credit. Harmonic counting can also
      incorporate additional byline information about equal contribution, or the
      elevated status of a corresponding last author. By contrast, several previously
      proposed counting schemes from the bibliometric literature including arithmetic,
      geometric and fractional counting, do not fit the empirical data as well and do
      not consistently meet the ethical criteria. In conclusion, harmonic counting
      would seem to provide unrivalled accuracy, fairness and flexibility to the long
      overdue task of standardizing bibliometric allocation of publication and citation
      credit.

PMID- 20700373
TI  - Collaboration in sensor network research: an in-depth longitudinal analysis of
      assortative mixing patterns.
AB  - Many investigations of scientific collaboration are based on statistical analyses
      of large networks constructed from bibliographic repositories. These
      investigations often rely on a wealth of bibliographic data, but very little or
      no other information about the individuals in the network, and thus, fail to
      illustrate the broader social and academic landscape in which collaboration takes
      place. In this article, we perform an in-depth longitudinal analysis of a
      relatively small network of scientific collaboration (N = 291) constructed from
      the bibliographic record of a research centerin the development and application
      of wireless and sensor network technologies. We perform a preliminary analysis of
      selected structural properties of the network, computing its range, configuration
      and topology. We then support our preliminary statistical analysis with an in
      depth temporal investigation of the assortative mixing of selected node
      characteristics, unveiling the researchers' propensity to collaborate
      preferentially with others with a similar academic profile. Our qualitative
      analysis of mixing patterns offers clues as to the nature of the scientific
      community being modeled in relation to its organizational, disciplinary,
      institutional, and international arrangements of collaboration.

PMID- 20700374
TI  - The impact of Schiff bases on antibiotic production by Streptomyces
      hygroscopicus.
AB  - A media consisting of isatin-Schiff bases (isatin-3-thiosemicarbazone, isatin-3
      semicarbazone, and isatin-3-phenylhydrazone) was developed to maximize the
      production of antibiotics Hexaene H-85 and Azalomycine B by Streptomyces
      hygroscopicus. The media isatin-3-thiosemicarbazone resulted in the maximum
      antibiotics concentration of 372 mug cm(-3) for Hexaene H-85 and 118 mug cm(-3)
      for Azalomycine B. The impact of modified media on soil morphology also was
      investigated.

PMID- 20700375
TI  - Leadership = Communication? The Relations of Leaders' Communication Styles with
      Leadership Styles, Knowledge Sharing and Leadership Outcomes.
AB  - PURPOSE: The purpose of this study was to investigate the relations between
      leaders' communication styles and charismatic leadership, human-oriented
      leadership (leader's consideration), task-oriented leadership (leader's
      initiating structure), and leadership outcomes. METHODOLOGY: A survey was
      conducted among 279 employees of a governmental organization. The following six
      main communication styles were operationalized: verbal aggressiveness,
      expressiveness, preciseness, assuredness, supportiveness, and argumentativeness.
      Regression analyses were employed to test three main hypotheses. FINDINGS: In
      line with expectations, the study showed that charismatic and human-oriented
      leadership are mainly communicative, while task-oriented leadership is
      significantly less communicative. The communication styles were strongly and
      differentially related to knowledge sharing behaviors, perceived leader
      performance, satisfaction with the leader, and subordinate's team commitment.
      Multiple regression analyses showed that the leadership styles mediated the
      relations between the communication styles and leadership outcomes. However,
      leader's preciseness explained variance in perceived leader performance and
      satisfaction with the leader above and beyond the leadership style variables.
      IMPLICATIONS: This study offers potentially invaluable input for leadership
      training programs by showing the importance of leader's supportiveness,
      assuredness, and preciseness when communicating with subordinates.
      ORIGINALITY/VALUE: Although one of the core elements of leadership is
      interpersonal communication, this study is one of the first to use a
      comprehensive communication styles instrument in the study of leadership.

PMID- 20700377
TI  - Concurrent Validity of the Child Behavior Checklist DSM-Oriented Scales:
      Correspondence with DSM Diagnoses and Comparison to Syndrome Scales.
AB  - This study used receiver operating characteristic (ROC) methodology and
      discriminative analyses to examine the correspondence of the Child Behavior
      Checklist (CBCL) rationally-derived DSM-oriented scales and empirically-derived
      syndrome scales with clinical diagnoses in a clinic-referred sample of children
      and adolescents (N = 476). Although results demonstrated that the CBCL Anxiety,
      Affective, Attention Deficit/Hyperactivity, Oppositional and Conduct Problems DSM
      oriented scales corresponded significantly with related clinical diagnoses
      derived from parent-based structured interviews, these DSM-oriented scales did
      not evidence significantly greater correspondence with clinical diagnoses than
      the syndrome scales in all cases but one. The DSM-oriented Anxiety Problems scale
      was the only scale that evidenced significantly greater correspondence with
      diagnoses above its syndrome scale counterpart -the Anxious/Depressed scale. The
      recently developed and rationally-derived DSM-oriented scales thus generally do
      not add incremental clinical utility above that already afforded by the syndrome
      scales with respect to corresponding with diagnoses. Implications of these
      findings are discussed.

PMID- 20700376
TI  - Natural products in modern life science.
AB  - With a realistic threat against biodiversity in rain forests and in the sea, a
      sustainable use of natural products is becoming more and more important. Basic
      research directed against different organisms in Nature could reveal unexpected
      insights into fundamental biological mechanisms but also new pharmaceutical or
      biotechnological possibilities of more immediate use. Many different strategies
      have been used prospecting the biodiversity of Earth in the search for novel
      structure-activity relationships, which has resulted in important discoveries in
      drug development. However, we believe that the development of multidisciplinary
      incentives will be necessary for a future successful exploration of Nature. With
      this aim, one way would be a modernization and renewal of a venerable proven
      interdisciplinary science, Pharmacognosy, which represents an integrated way of
      studying biological systems. This has been demonstrated based on an explanatory
      model where the different parts of the model are explained by our ongoing
      research. Anti-inflammatory natural products have been discovered based on
      ethnopharmacological observations, marine sponges in cold water have resulted in
      substances with ecological impact, combinatory strategy of ecology and chemistry
      has revealed new insights into the biodiversity of fungi, in depth studies of
      cyclic peptides (cyclotides) has created new possibilities for engineering of
      bioactive peptides, development of new strategies using phylogeny and chemography
      has resulted in new possibilities for navigating chemical and biological space,
      and using bioinformatic tools for understanding of lateral gene transfer could
      provide potential drug targets. A multidisciplinary subject like Pharmacognosy,
      one of several scientific disciplines bridging biology and chemistry with
      medicine, has a strategic position for studies of complex scientific questions
      based on observations in Nature. Furthermore, natural product research based on
      intriguing scientific questions in Nature can be of value to increase the
      attraction for young students in modern life science.

PMID- 20700378
TI  - Do Automatic Self-Associations Relate to Suicidal Ideation?
AB  - Dysfunctional self-schemas are assumed to play an important role in suicidal
      ideation. According to recent information-processing models, it is important to
      differentiate between 'explicit' beliefs and automatic associations. Explicit
      beliefs stem from the weighting of propositions and their corresponding 'truth'
      values, while automatic associations reflect more simple associations in memory.
      Both types of associations are assumed to have different functional properties
      and both may be involved in suicidal ideation. Thus far, studies into self
      schemas and suicidal ideation focused on the more explicit, consciously
      accessible traces of self-schemas and predominantly relied on self-report
      questionnaires or interviews. To complement these 'explicit' findings and more
      directly tap into self-schemas, this study investigated automatic self
      associations in a large scale community sample that was part of the Netherlands
      Study of Depression and Anxiety (NESDA). The results showed that automatic self
      associations of depression and anxiety were indeed significantly related to
      suicidal ideation and past suicide attempt. Moreover, the interactions between
      automatic self-depressive (anxious) associations and explicit self-depressive
      (anxious) beliefs explained additional variance over and above explicit self
      beliefs. Together these results provide an initial insight into one explanation
      of why suicidal patients might report difficulties in preventing and managing
      suicidal thoughts.

PMID- 20700379
TI  - Organic aerosol formation in citronella candle plumes.
AB  - Citronella candles are widely used as insect repellants, especially outdoors in
      the evening. Because these essential oils are unsaturated, they have a unique
      potential to form secondary organic aerosol (SOA) via reaction with ozone, which
      is also commonly elevated on summer evenings when the candles are often in use.
      We investigated this process, along with primary aerosol emissions, by briefly
      placing a citronella tealight candle in a smog chamber and then adding ozone to
      the chamber. In repeated experiments, we observed rapid and substantial SOA
      formation after ozone addition; this process must therefore be considered when
      assessing the risks and benefits of using citronella candle to repel insects.

PMID- 20700380
TI  - The solar eclipse and associated atmospheric variations observed in South Korea
      on 22 July 2009.
AB  - A partial solar eclipse occurred in South Korea on 22 July 2009. It started at
      09:30 a.m. and lasted until 12:14 LST with coverage of between 76.8% and 93.1% of
      the sun. The observed atmospheric effects of the eclipse are presented. It was
      found that from the onset of the eclipse, solar radiation was reduced by as much
      as 88.1 approximately 89.9% at the present research centre. Also, during the
      eclipse, air temperature decreased slightly or remained almost unchanged. After
      the eclipse, however, it rose by 2.5 to 4.5 degrees C at observed stations.
      Meanwhile, relative humidity increased and wind speeds were lowered by the
      eclipse. Ground-level ozone was observed to decrease during the event.

PMID- 20700381
TI  - Research on flux of dry atmospheric falling dust and its characterization in a
      subtropical city, Guangzhou, South China.
AB  - Guangzhou is the central city in the Pearl River Delta (PRD), China, and is one
      of the most polluted cities in the world. To characterize the ambient falling
      dust pollution, two typical sampling sites: urban (Wushan) and suburban
      (University Town) areas in Guangzhou city were chosen for falling dust collection
      over 1 year at time intervals of 1 or 2 months. The flux of dry deposition was
      calculated. In addition, mineral composition and morphology of atmospheric
      falling dust were studied by X-ray diffraction, scanning electron microscopy, and
      microscopic observation. The results revealed that the dust flux in Guangzhou
      city was 3.34-3.78 g/(m(2) month) during the study period. The main minerals in
      the dust were quartz, illite, calcite, kaolinite, gypsum, plagioclase, dolomite,
      and amorphous matter. The morphological types included grained and flaky
      individual minerals, chain-like aggregates, spherical flying beads, and irregular
      aggregates, with the chain-like and spherical aggregates indicators of industrial
      ash. The major dusts were derived from industrial and construction activities.
      The gypsum present in the dust collected in winter season was not only derived
      from cement dust but may also have originated from the reaction of calcic
      material with sulfuric acids resulting from photooxidation of SO(x) and NO(x),
      which confirmed serious air pollution due to SO(x) and NO(x) in Guangzhou. The
      abatement of fossil fuel combustion emissions and construction dust will have a
      significant beneficial effect on dust reduction.

PMID- 20700382
TI  - Immunohistochemical Distribution of PlexinA4 in the Adult Rat Central Nervous
      System.
AB  - PlexinA4 is the latest member to be identified of the PlexinA subfamily, critical
      transducers of class 3 semaphorin signaling as co-receptors to neuropilins 1 and
      2. Despite functional information regarding the role of PlexinA4 in development
      and guidance of specific neuronal pathways, little is known about its
      distribution in the adult central nervous system (CNS). Here we report an in
      depth immunohistochemical analysis of PlexinA4 expression in the adult rat CNS.
      PlexinA4 staining was present in neurons and fibers throughout the brain and
      spinal cord, including neocortex, hippocampus, lateral hypothalamus, red nucleus,
      facial nucleus, and the mesencephalic trigeminal nucleus. PlexinA4 antibodies
      labeled fibers in the lateral septum, nucleus accumbens, several thalamic nuclei,
      substantia nigra pars reticulata, zona incerta, pontine reticular region, as well
      as in several cranial nerve nuclei. This constitutes the first detailed
      description of the topographic distribution of PlexinA4 in the adult CNS and will
      set the basis for future studies on the functional implications of PlexinA4 in
      adult brain physiology.

PMID- 20700383
TI  - Cognitive rehabilitation of episodic memory disorders: from theory to practice.
AB  - Memory disorders are among the most frequent and most debilitating cognitive
      impairments following acquired brain damage. Cognitive remediation strategies
      attempt to restore lost memory capacity, provide compensatory techniques or teach
      the use of external memory aids. Memory rehabilitation has strongly been
      influenced by memory theory, and the interaction between both has stimulated the
      development of techniques such as spaced retrieval, vanishing cues or errorless
      learning. These techniques partly rely on implicit memory and therefore enable
      even patients with dense amnesia to acquire new information. However, knowledge
      acquired in this way is often strongly domain-specific and inflexible. In
      addition, individual patients with amnesia respond differently to distinct
      interventions. The factors underlying these differences have not yet been
      identified. Behavioral management of memory failures therefore often relies on a
      careful description of environmental factors and measurement of associated
      behavioral disorders such as unawareness of memory failures. The current evidence
      suggests that patients with less severe disorders benefit from self-management
      techniques and mnemonics whereas rehabilitation of severely amnesic patients
      should focus on behavior management, the transmission of domain-specific
      knowledge through implicit memory processes and the compensation for memory
      deficits with memory aids.

PMID- 20700384
TI  - Neuromechanical simulation.
AB  - The importance of the interaction between the body and the brain for the control
      of behavior has been recognized in recent years with the advent of
      neuromechanics, a field in which the coupling between neural and biomechanical
      processes is an explicit focus. A major tool used in neuromechanics is
      simulation, which connects computational models of neural circuits to models of
      an animal's body situated in a virtual physical world. This connection closes the
      feedback loop that links the brain, the body, and the world through sensory
      stimuli, muscle contractions, and body movement. Neuromechanical simulations
      enable investigators to explore the dynamical relationships between the brain,
      the body, and the world in ways that are difficult or impossible through
      experiment alone. Studies in a variety of animals have permitted the analysis of
      extremely complex and dynamic neuromechanical systems, they have demonstrated
      that the nervous system functions synergistically with the mechanical properties
      of the body, they have examined hypotheses that are difficult to test
      experimentally, and they have explored the role of sensory feedback in
      controlling complex mechanical systems with many degrees of freedom. Each of
      these studies confronts a common set of questions: (i) how to abstract key
      features of the body, the world and the CNS in a useful model, (ii) how to ground
      model parameters in experimental reality, (iii) how to optimize the model and
      identify points of sensitivity and insensitivity, and (iv) how to share
      neuromechanical models for examination, testing, and extension by others.

PMID- 20700385
TI  - Glutamatergic and resting-state functional connectivity correlates of severity in
      major depression - the role of pregenual anterior cingulate cortex and anterior
      insula.
AB  - Glutamatergic mechanisms and resting-state functional connectivity alterations
      have been recently described as factors contributing to major depressive disorder
      (MDD). Furthermore, the pregenual anterior cingulate cortex (pgACC) seems to play
      an important role for major depressive symptoms such as anhedonia and impaired
      emotion processing. We investigated 22 MDD patients and 22 healthy subjects using
      a combined magnetic resonance spectroscopy (MRS) and resting-state functional
      magnetic resonance imaging (fMRI) approach. Severity of depression was rated
      using the 21-item Hamilton depression scale (HAMD) and patients were divided into
      severely and mildly depressed subgroups according to HAMD scores. Because of
      their hypothesized role in depression we investigated the functional connectivity
      between pgACC and left anterior insular cortex (AI). The sum of Glutamate and
      Glutamine (Glx) in the pgACC, but not in left AI, predicted the resting-state
      functional connectivity between the two regions exclusively in depressed
      patients. Furthermore, functional connectivity between these regions was
      significantly altered in the subgroup of severely depressed patients (HAMD > 15)
      compared to healthy subjects and mildly depressed patients. Similarly the Glx
      ratios, relative to Creatine, in the pgACC were lowest in severely depressed
      patients. These findings support the involvement of glutamatergic mechanisms in
      severe MDD which are related to the functional connectivity between pgACC and AI
      and depression severity.

PMID- 20700386
TI  - Reward sensitivity for a palatable food reward peaks during pubertal
      developmental in rats.
AB  - Puberty is a critical period for the initiation of drug use and abuse. Because
      early drug use onset often accounts for a more severe progression of addiction,
      it is of importance to understand the underlying mechanisms and
      neurodevelopmental changes during puberty that are contributing to enhanced
      reward processing in teenagers. The present study investigated the progression of
      reward sensitivity toward a natural food reward over the whole course of
      adolescence in male rats (postnatal days 30-90) by monitoring consummatory,
      motivational behavior and neurobiological correlates of reward. Using a limited
      free intake paradigm, consumption of sweetened condensed milk (SCM) was measured
      repeatedly in adolescent and adult rats. Additionally, early- and mid-pubertal
      animals were tested in Progressive Ratio responding for SCM and c-fos protein
      expression in reward-associated brain structures was examined after odor
      conditioning for SCM. We found a transient increase in SCM consumption and
      motivational incentive for SCM during puberty. This increased reward sensitivity
      was most pronounced around mid-puberty. The behavioral findings are paralleled by
      enhanced c-fos staining in reward-related structures revealing an intensified
      neuronal response after reward-cue presentation, distinctive for pubertal
      animals. Taken together, these data indicate an increase in reward sensitivity
      during adolescence accompanied by enhanced responsiveness of reward-associated
      brain structures to incentive stimuli, and it seems that both is strongly
      pronounced around mid-puberty. Therefore, higher reward sensitivity during
      pubertal maturation might contribute to the enhanced vulnerability of teenagers
      for the initiation of experimental drug use.

PMID- 20700387
TI  - A role for compromise: synaptic inhibition and electrical coupling interact to
      control phasing in the leech heartbeat CpG.
AB  - How can flexible phasing be generated by a central pattern generator (CPG)? To
      address this question, we have extended an existing model of the leech heartbeat
      CPG's timing network to construct a model of the CPG core and explore how
      appropriate phasing is set up by parameter variation. Within the CPG, the phasing
      among premotor interneurons switches regularly between two well defined states -
      synchronous and peristaltic. To reproduce experimentally observed phasing, we
      varied the strength of inhibitory synaptic and excitatory electrical input from
      the timing network to follower premotor interneurons. Neither inhibitory nor
      electrical input alone was sufficient to produce proper phasing on both sides,
      but instead a balance was required. Our model suggests that the different phasing
      of the two sides arises because the inhibitory synapses and electrical coupling
      oppose one another on one side (peristaltic) and reinforce one another on the
      other (synchronous). Our search of parameter space defined by the strength of
      inhibitory synaptic and excitatory electrical input strength led to a CPG model
      that well approximates the experimentally observed phase relations. The strength
      values derived from this analysis constitute model predictions that we tested by
      measurements made in the living system. Further, variation of the intrinsic
      properties of follower interneurons showed that they too systematically influence
      phasing. We conclude that a combination of inhibitory synaptic and excitatory
      electrical input interacting with neuronal intrinsic properties can flexibly
      generate a variety of phase relations so that almost any phasing is possible.

PMID- 20700388
TI  - On the structure of solutions to a class of quasilinear elliptic Neumann
      problems. Part II.
AB  - We continue our work (Y. Li, C. Zhao in J Differ Equ 212:208-233, 2005) to study
      the structure of positive solutions to the equation epsilon(m) Delta(m)u - u(m-1)
      + f(u) = 0 with homogeneous Neumann boundary condition in a smooth bounded domain
      of RN (N >/= 2). First, we study subcritical case for 2 < m < N and show that
      after passing by a sequence positive solutions go to a constant in C(1, alpha)
      sense as epsilon --> infinity. Second, we study the critical case for 1 < m < N
      and prove that there is a uniform upper bound independent of epsilon in [1,
      infinity) for the least-energy solutions. Third, we show that in the critical
      case for 1 < m </= 2 the least energy solutions must be a constant if epsilon is
      sufficiently large and for 2 < m < N the least energy solutions go to a constant
      in C(1, alpha) sense as epsilon --> infinity.

PMID- 20700389
TI  - Sibling Relationships during the Transition to Adulthood.
AB  - Recent research has shed new light on individual development during the early
      adulthood years, yet few investigators have examined sibling relationships during
      this stage of life. These relationships undergo transformations as individuals
      enter adult roles and orient their lives towards friends and romantic partners
      and establish independence from parents and siblings. This review examines major
      life events and role transitions such as leaving home, completing school,
      obtaining employment, getting married, and having children that influence
      individuals and their sibling relationships. In addition, the review considers
      how sibling relationships may affect individuals during the transition to
      adulthood, and considers the context of family and culture. The article concludes
      with suggestions for future research on sibling relationships during early
      adulthood and beyond.

PMID- 20700390
TI  - Teasing apart the heterogeneity of autism: Same behavior, different brains in
      toddlers with fragile X syndrome and autism.
AB  - To examine brain volumes in substructures associated with the behavioral features
      of children with FXS compared to children with idiopathic autism and controls. A
      cross-sectional study of brain substructures was conducted at the first time
      point as part of an ongoing longitudinal MRI study of brain development in FXS.
      The study included 52 boys between 18-42 months of age with FXS and 118
      comparison children (boys with autism-non FXS, developmental-delay, and typical
      development). Children with FXS and autistic disorder had substantially enlarged
      caudate volume and smaller amygdala volume; whereas those children with autistic
      disorder without FXS (i.e., idiopathic autism) had only modest enlargement in
      their caudate nucleus volumes but more robust enlargement of their amygdala
      volumes. Although we observed this double dissociation among selected brain
      volumes, no significant differences in severity of autistic behavior between
      these groups were observed. This study offers a unique examination of early brain
      development in two disorders, FXS and idiopathic autism, with overlapping
      behavioral features, but two distinct patterns of brain morphology. We observed
      that despite almost a third of our FXS sample meeting criteria for autism, the
      profile of brain volume differences for children with FXS and autism differed
      from those with idiopathic autism. These findings underscore the importance of
      addressing heterogeneity in studies of autistic behavior.

PMID- 20700391
TI  - Perceived Racial Discrimination and Self-Esteem in African American Youth: Racial
      Socialization as a Protective Factor.
AB  - Racial socialization was examined as a protective factor that might buffer
      African American youth from the negative effects of perceived racial
      discrimination. Two types of racial socialization were examined: messages about
      race pride and preparation for bias. One hundred twenty-eight eighth-grade
      African American students participated in the study. As anticipated, both types
      of socialization moderated the relationship between discrimination and self
      esteem. The negative relationship between perceived discrimination and self
      esteem was mitigated for youth who reported more messages about race pride and a
      moderate amount of preparation for bias from their parents. In contrast, low race
      pride socialization and both high and low preparation for bias were associated
      with a negative relationship between perceived discrimination and self-esteem.

PMID- 20700393
TI  - Theta motion processing in fruit flies.
AB  - The tiny brains of insects presumably impose significant computational
      limitations on algorithms controlling their behavior. Nevertheless, they perform
      fast and sophisticated visual maneuvers. This includes tracking features composed
      of second-order motion, in which the feature is defined by higher-order image
      statistics, but not simple correlations in luminance. Flies can track the true
      direction of even theta motions, in which the first-order (luminance) motion is
      directed opposite the second-order moving feature. We exploited this paradoxical
      feature tracking response to dissect the particular image properties that flies
      use to track moving objects. We find that theta motion detection is not simply a
      result of steering toward any spatially restricted flicker. Rather, our results
      show that fly high-order feature tracking responses can be broken down into
      positional and velocity components - in other words, the responses can be modeled
      as a superposition of two independent steering efforts. We isolate these elements
      to show that each has differing influence on phase and amplitude of steering
      responses, and together they explain the time course of second-order motion
      tracking responses during flight. These observations are relevant to natural
      scenes, where moving features can be much more complex.

PMID- 20700392
TI  - Imaging and recording subventricular zone progenitor cells in live tissue of
      postnatal mice.
AB  - The subventricular zone (SVZ) is one of two regions where neurogenesis persists
      in the postnatal brain. The SVZ, located along the lateral ventricle, is the
      largest neurogenic zone in the brain that contains multiple cell populations
      including astrocyte-like cells and neuroblasts. Neuroblasts migrate in chains to
      the olfactory bulb where they differentiate into interneurons. Here, we discuss
      the experimental approaches to record the electrophysiology of these cells and
      image their migration and calcium activity in acute slices. Although these
      techniques were in place for studying glial cells and neurons in mature networks,
      the SVZ raises new challenges due to the unique properties of SVZ cells, the
      cellular diversity, and the architecture of the region. We emphasize different
      methods, such as the use of transgenic mice and in vivo electroporation that
      permit identification of the different SVZ cell populations for patch clamp
      recording or imaging. Electroporation also permits genetic labeling of cells
      using fluorescent reporter mice and modification of the system using either RNA
      interference technology or floxed mice. In this review, we aim to provide
      conceptual and technical details of the approaches to perform
      electrophysiological and imaging studies of SVZ cells.

PMID- 20700395
TI  - Possible Role of Plant Allelochemical in Clearance of Bacteria from the Gut of
      Spruce Budworm, Choristoneura fumiferana.
AB  - Field results, using Bacillus thuringiensis delta-endotoxin in controlling spruce
      budworms, Choristoneura fumiferana, are far less satisfactory than those from the
      laboratoriesThe role of septicemia has also been shown to be important in
      mortality. However its relationship with insect diet has not been studied. Insect
      gut juice from spruce budworm fed on balsam foliage inhibited bacterial growth.
      Such activity has not been observed in the gut juice from insects fed on
      artificial diet. Moreover, when bacteria were given to the insects orally, and
      the insects then fed on balsam foliage overnight, little or no bacterial colonies
      could be detected in their gut juices in the tryptic soy agar plates. Such
      bacterial growth inhibition activity could also be found in the water extract of
      balsam foliage, and was suggested to be due to tannins. This result explains the
      role of allelochemicals affecting septicemia in spruce budworms, and hence the
      efficacy, when using Bacillus thuringinesis delta-endotoxin as a biologic control
      agent.

PMID- 20700394
TI  - Actual Role of Platelet Glycoprotein IIb/IIIa Receptor Inhibitors as Adjunctive
      Pharmacological Therapy to Primary Angioplasty in Acute Myocardial Infarction: In
      the Light of Recent Randomized Trials and Observational Studies with Bivalirudin.
AB  - Strategies for preventing ischemic complications during percutaneous coronary
      interventions (PCI) in the setting of acute myocardial infarction (AMI) have
      focused on the platelet surface-membrane glycoprotein (GP) IIb/IIIa receptor. The
      platelet GP IIb/IIIa receptor inhibitors, by blocking the final common pathway of
      platelet aggregation, have become a breakthrough in the management of acute
      coronary syndromes. Current adjuvant pharmacological therapy of AMI with aspirin,
      clopidogrel, unfractionated heparin (UH), and platelet GP IIb/IIIa inhibitors
      provides useful therapeutic benefits. Although the use of more potent
      antithrombin and antiplatelet agents during PCI in AMI has reduced the rate of
      ischemic complications, in parallel, the rate of bleeding has increased. Several
      studies have reported an association between bleeding after PCI and an increase
      in morbidity and mortality. Therefore, investigational studies have focused in
      pharmacological agents that would reduce bleeding complications without
      compromising the rate of major adverse cardiovascular events. Based on the
      results of several randomized trials, abciximab with UH, aspirin and clopidogrel
      have become a standard adjunctive therapy with primary PCI for AMI. However, some
      of the trials were done before the use of stents and the widespread use of
      thienopyridines. In addition, GP IIb/IIIa inhibitors use have been associated
      with thrombocytopenia, high rates of bleeding, and the need for transfusions,
      which increase costs, length of hospital stay, and mortality. On the other hand,
      in the stent era, bivalirudin, a semi-synthetic direct thrombin inhibitor, has
      recently been shown to provide similar efficacy with less bleeding compared with
      unfractionated heparin plus platelet GP IIb/IIIa inhibitors in AMI patients
      treated with primary PCI. The impressive results of this recent randomized trial
      and other observational studies make a strong argument for the use of bivalirudin
      rather than heparin plus GP IIb/IIIa inhibitors for the great majority of
      patients with AMI treated with primary PCI. However, some controversial results
      and limitations in the studies with bivalirudin exert some doubts in the future
      widespread use of this drug.

PMID- 20700396
TI  - Glycoprotein C Gene of Caprine Herpesvirus Type 1 Contains Short Sequence Repeats
      (SSR).
AB  - Caprine herpesvirus 1 (CpHV-1) is responsible for vaginal and respiratory disease
      in goats. Infection by vaginal route is usually restricted to the genital tract
      whereas by nasal route the virus can spread throughout the body. In order to
      evaluate genomic diversity, nucleotide sequences of glycoprotein C (gC) of 13
      (n.8 vaginal, n.5 nasal) CpHV-1 strains were analyzed. Amino acid (aa) sequences
      showed a variable number of short sequence repeats (SSR). Nucleotide and amino
      acid sequences of amplified products showed to contain a variable number of short
      sequence repeats among the examined strains. These results indicated that CpHV-1
      isolates had genetic diversity in the gC gene regarding the number of SSR: 4 SSR
      of 60 bp in one strain, 2 SSR of 30 bp in seven strains and 1 SSR of 15 bp in
      three strains. Two strains had no SSR.

PMID- 20700397
TI  - Understanding Human Coronavirus HCoV-NL63.
AB  - Even though coronavirus infection of humans is not normally associated with
      severe diseases, the identification of the coronavirus responsible for the
      outbreak of severe acute respiratory syndrome showed that highly pathogenic
      coronaviruses can enter the human population. Shortly thereafter, in Holland in
      2004, another novel human coronavirus (HCoV-NL63) was isolated from a seven-month
      old infant suffering from respiratory symptoms. This virus has subsequently been
      identified in various countries, indicating a worldwide distribution. HCoV-NL63
      has been shown to infect mainly children and the immunocommpromised, who
      presented with either mild upper respiratory symptoms (cough, fever and
      rhinorrhoea) or more serious lower respiratory tract involvement such as
      bronchiolitis and croup, which was observed mainly in younger children. In fact,
      HCoV-NL63 is the aetiological agent for up to 10% of all respiratory diseases.
      This review summarizes recent findings of human coronavirus HCoV-NL63 infections,
      including isolation and identification, phylogeny and taxonomy, genome structure
      and transcriptional regulation, transmission and pathogenesis, and detection and
      diagnosis.

PMID- 20700398
TI  - Anti-Herpetic Activity of Callissia fragrans and Simmondsia chinensis Leaf
      Extracts In Vitro.
AB  - The antiviral activity of Callissia fragrans and Simnondsia chinensis aquatic and
      ethanol leaf extracts, as well as purified fractions from these extracts was
      studied against herpetic viruses in vitro. Ethanol extract of C. fragrans
      effectively inhibited the infection of Vero cells by HSV-1, HSV-2 in vitro, while
      its aquatic extract inhibited only VZV. Although S. chinensis leaf extract
      strongly inhibited all studied viruses, the selectivity index of this extract was
      very low, due to its high toxicity. However, the majority of its fractions showed
      low toxicity and higher antiviral activity and therefore very high SI. Strong
      interactions between virus and extracts were found.

PMID- 20700399
TI  - Differential roles for octanoylated and decanoylated ghrelins in regulating
      appetite and metabolism.
AB  - Since its identification in 1999, ghrelin has been identified in all vertebrate
      groups. The "active core" of ghrelin is highly conserved among vertebrates,
      suggesting its biological activity to be also conserved. In fish, both acylated
      forms of ghrelin have been identified; however, the ratio of the ghrelin-C8 to
      ghrelin-C10 is not as great as observed in mammals. In the tilapia (Oreochromis
      mossambicus), ghrelin-C10 is the major form of ghrelin. Since fish are known to
      inhabit every ecological niche on earth, studies on fish have provided valuable
      insight into vertebrate physiology in general; it is likely that understanding
      the role of both acylated forms of ghrelin, in more detail, in fish will result
      into novel insights in the biology of ghrelin within vertebrates. In this paper
      we discuss ghrelin's role in regulating appetite and metabolism in fish, in
      general, and provide evidence that the two tilapia ghrelins exhibit different
      biological roles.

PMID- 20700400
TI  - Ghrelin in diabetes and metabolic syndrome.
AB  - Metabolic syndrome is a cluster of related risk factors for cardiovascular
      disease, type 2 diabetes and liver disease. Obesity, which has become a global
      public health problem, is one of the major risk factors for development of
      metabolic syndrome and type 2 diabetes. Obesity is a complex disease, caused by
      the interplay between environmental and genetic factors. Ghrelin is one of the
      circulating peptides, which stimulates appetite and regulates energy balance, and
      thus is one of the candidate genes for obesity and T2DM. During the last years
      both basic research and genetic association studies have revealed association
      between the ghrelin gene and obesity, metabolic syndrome or type 2 diabetes.

PMID- 20700402
TI  - Ghrelin and metabolic surgery.
AB  - Metabolic surgery is the most effective treatment for morbid obesity. Ghrelin has
      been implicated to play a role in the success of these procedures. Furthermore,
      these operations have been used to study the gut-brain axis. This article
      explores this interaction, reviewing the available data on changes in ghrelin
      levels after different surgical procedures.

PMID- 20700401
TI  - Effect of ghrelin on glucose-insulin homeostasis: therapeutic implications.
AB  - Ghrelin is a 28-amino-acid peptide that displays a strong growth hormone- (GH-)
      releasing activity through the activation of the growth hormone secretagogue
      receptor (GHSR). The first studies about role of ghrelin were focused on its
      orexigenic ability, but despite indisputable pharmacological data, the evidence
      for a physiological role for ghrelin in the control of appetite is much less
      clear. Mice with targeted deletion of either ghrelin or the GHSR exhibit an
      essentially normal metabolic phenotype when fed a regular chow diet, suggesting
      that ghrelin may have a redundant role in the regulation of food intake. RNAs for
      ghrelin as well as GHSR are expressed in the pancreas of rats and humans and
      several studies propose that ghrelin could have an important function in glucose
      homeostasis and insulin release, independent of GH secretion. Low plasma ghrelin
      levels are associated with elevated fasting insulin levels and insulin
      resistance, suggesting both physiological and pathophysiological roles for
      ghrelin. For this reason, at least theoretically, ghrelin and/or its signalling
      manipulation could be useful for the treatment or prevention of diseases of
      glucose homeostasis such as type 2 diabetes.

PMID- 20700404
TI  - Different types of resistant starch elicit different glucose reponses in humans.
AB  - The purpose of this study was to determine whether different types of resistant
      starch (RS) elicited different glycemic responses. Eleven healthy subjects
      consumed solutions containing 30 g of either dextrose (DEX), resistant starch
      type 2 (RS2), or cross-linked resistant wheat starch type 4 (RS4(XL)) on three
      separate occasions, which were assigned randomly. Finger stick blood samples were
      collected before and over the following two hours and measured for glucose. The
      incremental area under the curve (iAUC) for the glucose response was calculated
      for all trials. The two types of resistant starch significantly (P < .05)
      decreased iAUC compared with DEX. The response with RS4(XL) was significantly
      decreased compared with the RS2 trial. These data demonstrate that different
      types of resistant starch elicit significantly different glycemic responses.

PMID- 20700403
TI  - Ghrelin in female and male reproduction.
AB  - Ghrelin and one of its functional receptors, GHS-R1a (Growth Hormone Secretagogue
      Receptor 1a), were firstly studied about 15 years. Ghrelin is a multifunctional
      peptide hormone that affects several biological functions including food intake,
      glucose release, cell proliferation... Ghrelin and GHS-R1a are expressed in key
      cells of both male and female reproductive organs in several species including
      fishes, birds, and mammals suggesting a well-conserved signal through the
      evolution and a role in the control of fertility. Ghrelin could be a component of
      the complex series of nutrient sensors such as adipokines, and nuclear receptors,
      which regulate reproduction in function of the energy stores. The objective of
      this paper was to report the available information about the ghrelin system and
      its role at the level of the hypothalamic-pituitary-gonadal axis in both sexes.

PMID- 20700405
TI  - Sugar-Sweetened Beverage Intake Trends in US Adolescents and Their Association
      with Insulin Resistance-Related Parameters.
AB  - The purpose of this study was to evaluate current sugar-sweetened beverage (SSB)
      consumption trends and their association with insulin resistance-related
      metabolic parameters and anthropometric measurements by performing a cross
      sectional analysis of the NHANES data during the years 1988-1994 and 1999-2004.
      Main outcome measures included SSB consumption trends, a homeostasis model
      assessment of insulin resistance, blood pressure, waist circumference, body mass
      index, and fasting concentrations of total cholesterol, HDL-cholesterol, LDL
      cholesterol, and triglycerides. Although overall SSB consumption has increased,
      our data suggest that this increase was primarily due to an increase in the
      amount of SSBs consumed by males in the high-SSB intake group alone. Multivariate
      linear regression analyses also showed that increased SSB consumption was
      independently associated with many adverse health parameters. Factors other than
      SSB consumption must therefore be contributing to the increasing prevalence of
      obesity and metabolic syndrome in the majority of US children.

PMID- 20700406
TI  - Energy expenditure and physical activity in recovering malnourished infants.
AB  - Background. Malnourished infants are small for age and weight. Objectives.
      Determine profiles in 24-hour energy metabolism in recovering malnourished
      infants and compare to similarly aged healthy controls. Methods. 10 malnourished
      infants (58.1 +/- 5.9 cm, 7.7 +/- 5.6 months) were healthy prior to spending 22
      hours in the Enhanced Metabolic Testing Activity Chamber for measurement of EE
      (kcal/min), sleeping metabolic rate (SMR; kcal/min), respiratory quotient (RQ;
      VCO(2)/VO(2)), and physical activity (PA; oscillations in wt/min/kg body weight).
      Metabolic data were extrapolated to 24 hours (kcal/kg/d). Energy intake
      (kcal/kg/d) and the proportions (%) of carbohydrate, protein, and fat were
      calculated. Anthropometrics for malnourished infants were obtained. Statistical
      differences (P < .05) between groups were determined (SPSS, version 13). Results.
      In comparison to controls, malnourished infants were lighter (4.1 +/- 1.2 versus
      7.3 +/- 0.8 kg; P < .05), had less body fat % (10.3 +/- 7.6 versus 25.7 +/- 2.5),
      and lower BMI (12.0 +/- 1.7 versus 15.5 +/- 1.5; P < .05). In contrast, they had
      greater energy intake (142.7 +/- 14.6 versus 85.1 +/- 25.8; P < .05) with a
      greater percentage of carbohydrates (55.1 +/- 3.9 versus 47.2 +/- 5.2; P < .05).
      However, malnourished infants had greater 24-hour EE (101.3 +/- 20.1 versus 78.6
      +/- 8.4; P < .05), SMR (92.6 +/- 17.1 versus 65.0 +/- 3.9; P < .05), and RQ (1.00
      +/- 0.13 versus 0.86 +/- 0.08; P < .05) along with a lower amount of PA (2.3 +/-
      0.94 versus 4.0 +/- 1.5; P < .05). Conclusions. Malnourished infants require more
      energy, possibly for growth.

PMID- 20700407
TI  - Dietary glycemic index, dietary glycemic load, blood lipids, and coronary heart
      disease.
AB  - Objective. To examine the associations of dietary glycemic index (GI) and dietary
      glycemic load (GL) with blood lipid concentrations and coronary heart disease
      (CHD) in nondiabetic participants in the Health Worker Cohort Study (HWCS).
      Materials and Methods. A cross-sectional analysis was performed, using data from
      adults who participated in the HWCS baseline assessment. We collected information
      on participants' socio-demographic conditions, dietary patterns and physical
      activity via self-administered questionnaires. Dietary GI and dietary GL were
      measured using a validated food frequency questionnaire. Anthropometric and
      clinical measurements were assessed with standardized procedures. CHD risk was
      estimated according to the sex-specific Framingham prediction algorithms.
      Results. IIn the 5,830 individuals aged 20 to 70 who were evaluated, dietary GI
      and GL were significantly associated with HDL-C, LDL-C, LDL-C/HDL-C ratio, and
      triglycerides serum levels. Subjects with high dietary GI have a relative risk of
      1.56 (CI 95%; 1.13-2.14), and those with high dietary GL have a relative risk of
      2.64 (CI 95%; 1.15-6.58) of having an elevated CHD risk than those who had low
      dietary GI and GL. Conclusions. Our results suggest that high dietary GI and
      dietary GL could have an unfavorable effect on serum lipid levels, which are in
      turn associated with a higher CHD risk.

PMID- 20700408
TI  - Renal dysfunction, metabolic syndrome and cardiovascular disease mortality.
AB  - Background. Renal disease is commonly described as a complication of metabolic
      syndrome (MetS) but some recent studies suggest that Chronic Kidney disease (CKD)
      may actually antecede MetS. Few studies have explored the predictive utility of
      co-clustering CKD with MetS for cardiovascular disease (CVD) mortality. Methods.
      Data from a nationally representative sample of United States adults (NHANES) was
      utilized. A sample of 13115 non-pregnant individuals aged >/=35 years, with
      available follow-up mortality assessment was selected. Multivariable Cox
      Proportional hazard regression analysis techniques explored the relationship
      between co-clustered CKD, MetS and CVD mortality. Bayesian analysis techniques
      tested the predictive accuracy for CVD Mortality of two models using co-clustered
      MetS and CKD and MetS alone. Results. Co-clustering early and late CKD
      respectively resulted in statistically significant higher hazard for CVD
      mortality (HR = 1.80, CI = 1.45-2.23, and HR = 3.23, CI = 2.56-3.70) when
      compared with individuals with no MetS and no CKD. A model with early CKD and
      MetS has a higher predictive accuracy (72.0% versus 67.6%), area under the ROC
      (0.74 versus 0.66), and Cohen's kappa (0.38 versus 0.21) than that with MetS
      alone. Conclusion. The study findings suggest that the co-clustering of early CKD
      with MetS increases the accuracy of risk prediction for CVD mortality.

PMID- 20700409
TI  - Bariatric Revisionary Surgery for Failed or Complicated Vertical Banded
      Gastroplasty (VBG): Comparison of VBG Reoperation (re-VBG) versus Roux-en-Y
      Gastric Bypass-on-VBG (RYGB-on-VBG).
AB  - Background. Revision of failed bariatric procedures is a significant challenge
      for bariatric surgeons, because of the increasing number of recurring morbid
      obesity or complications, especially in patients with a previous Vertical Banded
      Gastroplasty (VBG). Methods. Since November 1998, 109 patients with failed or
      complicated VBG were followed in a retrospective study. 49 patients underwent re
      VBG and, since 2004, 60 underwent Roux-en-Y Gastric Bypass-on-Vertical Banded
      Gastroplasty (RYGB-on-VBG). Results. At 3 years follow-up, mean BMI decreased
      from 37.4 to 31.2 Kg/m(2) in the first group, and from 35.0 to 28.4 Kg/m(2) in
      the second. Early complications were 7 (14.3%) in the first group and 4 (6.5%) in
      the second; late complications were 33 (59.1%) and 11 (18.3%), respectively.
      Conclusion. Although both operations seem to be effective as bariatric revision
      procedures in terms of BMI, the mid-term outcomes of RYGB-on-VBG demonstrate the
      lowest rate of complications and better quality of life.

PMID- 20700410
TI  - Fitness versus Fatness and Insulin Resistance in U.S. Adolescents.
AB  - Background. The present study examined the relationship between insulin
      resistance and both waist circumference and cardiorespiratory fitness in U.S.
      adolescents. Methods. NHANES assessed a nationally representative sample of U.S.
      adolescents (12-18 yrs) between 1999-2002. Abdominal adiposity was estimated by
      waist circumference, overall adiposity by BMI, and cardiorespiratory fitness
      (maximal oxygen uptake (VO(2)max) from a treadmill exercise test). Insulin
      resistance was estimated from fasting insulin and glucose using the homeostatic
      model assessment method (i.e., HOMA) and was log-transformed. Results. 1078
      adolescents were included in the study. Positive correlations existed between
      lnHOMA and waist circumference (r = 0.59; r = 0.54) for boys and girls,
      respectively. lnHOMA and VO(2)max were inversely related in boys (r = -0.29) but
      not girls (r = -0.06). Gender-specific analyses by BMI category showed that the
      significant inverse relationship in lnHOMA and VO(2)max was primarily present in
      obese boys. Conclusion. Among adolescents, important gender and BMI differences
      exist in the relationship between insulin resistance and fitness. While waist
      circumference and BMI are important predictors in all children, fitness appears
      especially important in obese boys. These findings may have important
      implications for gender-specific interventions to prevent adult obesity and
      diabetes mellitus.

PMID- 20700411
TI  - Changes in Theory-Based Psychological Factors Predict Weight Loss in Women with
      Class III Obesity Initiating Supported Exercise.
AB  - Background. Psychological factors' effect on weight loss is poorly understood, in
      general, and specifically in the severely obese. Objective. To examine whether a
      behavioral model based on tenets of social cognitive and self-efficacy theory
      will increase understanding of the relationship between exercise and weight loss.
      Methods. Fifty-one women with severe obesity participated in a 24-week exercise
      and nutrition information treatment and were measured on changes in psychological
      factors and exercise attendance. Results. A significant portion of the variance
      in BMI change (adjusted for number of predictors) was accounted for by the
      behavioral model (R(2) (adj) = 0.23). Entry of exercise session attendance only
      marginally improved the prediction to 0.27. Only 19% of the weight lost was
      directly attributable to caloric expenditure from exercise. Conclusions. Findings
      suggest that participation in an exercise program affects weight loss through
      psychological pathways and, thus, may be important in the behavioral treatment of
      severe obesity.

PMID- 20700412
TI  - The Association between Childhood Overweight and Reflux Esophagitis.
AB  - Background. In adults, it has been shown that obesity is associated with
      gastroesophageal reflux disease (GERD) and GERD-related complications. There are
      sparse pediatric data demonstrating associations between childhood overweight and
      GERD. Objective. To investigate the association between childhood overweight and
      RE. Methods. We performed a retrospective chart review of 230 children (M : F =
      114 : 116) who underwent esophagogastroduodenoscopy (EGD) with biopsies between
      January 2000 and April 2006. Patient demographics, weight, height, clinical
      indications for the procedure, the prevalence of BMI classification groups, the
      prevalence of RE and usage of anti-reflux medications were reviewed. For these
      analyses, the overweight group was defined to include subjects with BMI>/= 85th
      percentile. The normal weight group was defined to include subjects with BMI 5th
      to 85th percentile. Results. Among the 230 subjects, 67 (29.1%) had BMI
      percentiles above the 85th percentile for age and gender. The prevalence of RE in
      the overweight group did not differ significantly from that in the normal weight
      group (23.9% versus 24.5%, resp.). Overweight subjects taking anti-reflux
      medications clearly demonstrated a higher prevalence of biopsy-proven RE compared
      to overweight subjects not taking anti-reflux medications (34.1% versus 7.7%, P =
      .009). Conclusions. There was no significant difference in the prevalence of
      biopsy-proven RE in the overweight group compared to the normal weight group.
      However, the prevalence of RE was significantly higher in overweight subjects on
      anti-reflux medications compared to overweight subjects not taking anti-reflux
      medications. This finding emphasizes the importance of early recognition and
      treatment of GERD for the overweight pediatric patients with symptoms in
      conjunction with weight loss program for this population to reduce long-term
      morbidities associated with GERD.

PMID- 20700413
TI  - Body weight control by a high-carbohydrate/low-fat diet slows the progression of
      diabetic kidney damage in an obese, hypertensive, type 2 diabetic rat model.
AB  - Obesity is one of several factors implicated in the genesis of diabetic
      nephropathy (DN). Obese, hypertensive, type 2 diabetic rats SHR/NDmcr-cp were
      given, for 12 weeks, either a normal, middle-carbohydrate/middle-fat diet (MC/MF
      group) or a high-carbohydrate/low-fat diet (HC/LF group). Daily caloric intake
      was the same in both groups. Nevertheless, the HC/LF group gained less weight.
      Despite equivalent degrees of hypertension, hyperglycemia, hyperlipidemia,
      hyperinsulinemia, and even a poorer glycemic control, the HC/LF group had less
      severe renal histological abnormalities and a reduced intrarenal advanced
      glycation and oxidative stress. Mediators of the renoprotection, specifically
      linked to obesity and body weight control, include a reduced renal inflammation
      and TGF-beta expression, together with an enhanced level of adiponectin.
      Altogether, these data identify a specific role of body weight control by a high
      carbohydrate/low-fat diet in the progression of DN. Body weight control thus
      impacts on local intrarenal advanced glycation and oxidative stress through
      inflammation and adiponectin levels.

PMID- 20700414
TI  - Design, synthesis, and analysis of minor groove binder pyrrolepolyamide-2'
      deoxyguanosine hybrids.
AB  - Pyrrolepolyamide-2'-deoxyguanosine hybrids (Hybrid 2 and Hybrid 3) incorporating
      the 3-aminopropionyl or 3-aminopropyl linker were designed and synthesized on the
      basis of previously reported results of a pyrrolepolyamide-adenosine hybrid
      (Hybrid 1). Evaluation of the DNA binding sequence selectivity of
      pyrrolepolyamide-2'-deoxyguanosine hybrids was performed by CD spectral and T(m)
      analyses. It was shown that Hybrid 3 possessed greater binding specificity than
      distamycin A, Hybrid 1 and Hybrid 2.

PMID- 20700415
TI  - Synthesis of Macrocyclic Hexaoxazole (6OTD) Dimers, Containing Guanidine and
      Amine Functionalized Side Chains, and an Evaluation of Their Telomeric G4
      Stabilizing Properties.
AB  - Structure-activity relationship studies were carried out on macrocyclic
      hexaoxazole (6OTD) dimers, whose core structure stabilizes telomeric G
      quadruplexes (G4). Two new 6OTD dimers having side chain amine and guanidine
      functional groups were synthesized and evaluated for their stabilizing ability
      against a telomeric G4 DNA sequence. The results show that the 6OTD dimers
      interact with the DNA to form 1:1 complexes and stabilize the antiparallel G4
      structure of DNA in the presence of potassium cation. The guanidine
      functionalized dimer displays a potent stabilizing ability of the G4 structure,
      as determined by using a FRET melting assay (DeltaT(m) = 14 degrees C).

PMID- 20700416
TI  - Expression levels of some antioxidant and epidermal growth factor receptor genes
      in patients with early-stage non-small cell lung cancer.
AB  - THIS STUDY WAS AIMED AT: (i) investigating the expression profiles of some
      antioxidant and epidermal growth factor receptor genes in cancerous and
      unaffected tissues of patients undergoing lung resection for non-small cell lung
      cancer (NSCLC) (cross-sectional phase), (ii) evaluating if gene expression levels
      at the time of surgery may be associated to patients' survival (prospective
      phase). Antioxidant genes included heme oxygenase 1 (HO-1), superoxide dismutase
      1 (SOD-1), and -2 (SOD-2), whereas epidermal growth factor receptor genes
      consisted of epidermal growth factor receptor (EGFR) and v-erb-b2 erythroblastic
      leukaemia viral oncogene homolog 2 (HER-2). Twenty-eight couples of lung biopsies
      were obtained and gene transcripts were quantified by Real Time RT-PCR. The
      average follow-up of patients lasted about 60 months. In the cancerous tissues,
      antioxidant genes were significantly hypo-expressed than in unaffected tissues.
      The HER-2 transcript levels prevailed in adenocarcinomas, whereas EGFR in
      squamocellular carcinomas. Patients overexpressing HER-2 in the cancerous tissues
      showed significantly lower 5-year survival than the others.

PMID- 20700417
TI  - Effect of Ionic Strength on Porphyrin Drugs Interaction with Quadruplex DNA
      Formed by the Promoter Region of C-myc and Bcl2 Oncogenes.
AB  - C-myc and Bcl2 are well characterized oncogenes that are capable of forming G
      quadruplex structures. Promoter regions of C-myc and Bcl2 forming G-quadruplex
      structures are chemically synthesized and G-quadruplex structure is formed in
      presence of 100 mM potassium ion. Three different porphyrin drugs, namely TMPyP2,
      TMPyP3, and TMPyP4 are allowed to interact with quadruplex DNA complex and the
      site and nature of interaction are studied. Drug interactions with quadruplex DNA
      were carried out in different potassium ionic strengths using fluorescence
      spectroscopy. It is found that fluorescence hypochromicity decreases with an
      increase in ionic strength in the case of TMPyP4, TMPyP3, and TMPyP2.
      Fluorescence titration studies and Job plots indicate that four molecules of
      TMPyP4, two molecules of TMPyP3 and TMPyP2 are interacting with one molecule of
      quadruplex DNA.

PMID- 20700418
TI  - Cation involvement in telomestatin binding to g-quadruplex DNA.
AB  - The binding mode of telomestatin to G-quadruplex DNA has been investigated using
      electrospray mass spectrometry, by detecting the intact complexes formed in
      ammonium acetate. The mass measurements show the incorporation of one extra
      ammonium ion in the telomestatin complexes. Experiments on telomestatin alone
      also show that the telomestatin alone is able to coordinate cations in a similar
      way as a crown ether. Finally, density functional theory calculations suggest
      that in the G-quadruplex-telomestatin complex, potassium or ammonium cations are
      located between the telomestatin and a G-quartet. This study underlines that
      monovalent cation coordination capabilities should be integrated in the rational
      design of G-quadruplex binding ligands.

PMID- 20700419
TI  - Inraoperative and Histological Visualization of Disrupted Vulnerable Plaques
      following Diagnostic Angiography of Moderate Carotid Stenosis.
AB  - Background. Digital subtraction angiography (DSA) remains an important tool for
      diagnosis of carotid stenosis but is associated with risk for periprocedural
      complications. This is the first report of direct intraoperative and
      histolopathologic visualization of DSA-related carotid plaque disruption. Case. A
      64-year-old man diagnosed to have a 60% right carotid stenosis received
      diagnostic DSA for therapeutic decision-making. He developed transient left hand
      numbness and weakness immediately after the procedure. Intraoperative imaging
      during carotid endarterectomy revealed a fragile plaque with sharp surface
      laceration and intraplaque hemorrhage at the bifurcation. Microscopy of the
      specimen demonstrated a large atheromatous plaque with fibrous hypertrophy and
      intraplaque hemorrhage filled with recent hemorrhagic debris. Conclusion. The
      visualized carotid lesion was more serious than expected, warning the danger of
      embolization or occlusion associated with the catheter maneuvers. Thus the
      highest level of practitioner training and technical expertise that ensures
      precise assessment of plaque characteristics should be encouraged.

PMID- 20700420
TI  - Choosing the optimal trigger point for analysis of movements after stroke based
      on magnetoencephalographic recordings.
AB  - The aim of this study was to select the optimal procedure for analysing motor
      fields (MF) and motor evoked fields (MEF) measured from brain injured patients.
      Behavioural pretests with patients have shown that most of them cannot stand
      measurements longer than 30 minutes and they also prefer to move the hand with
      rather short breaks between movements. Therefore, we were unable to measure the
      motor field (MF) optimally. Furthermore, we planned to use MEF to monitor
      cortical plasticity in a motor rehabilitation procedure. Classically, the MF
      analysis refers to rather long epochs around the movement onset (M-onset). We
      shortened the analysis epoch down to a range from 1000 milliseconds before until
      500 milliseconds after M-onset to fulfil the needs of the patients. Additionally,
      we recorded the muscular activity (EMG) by surface electrodes on the extensor
      carpi ulnaris and flexor carpi ulnaris muscles. Magnetoencephalographic (MEG)
      data were recorded from 9 healthy subjects, who executed horizontally brisk
      extension and flexion in the right wrist. Significantly higher MF dipole strength
      was found in data based on EMG-onset than in M-onset based data. There was no
      difference in MEF I dipole strength between the two trigger latencies. In
      conclusion, we recommend averaging in respect to the EMG-onset for the analysis
      of both components MF as well as MEF.

PMID- 20700421
TI  - Reliability, responsiveness, and validity of the visual analog fatigue scale to
      measure exertion fatigue in people with chronic stroke: a preliminary study.
AB  - Background and Purpose. Post-Stroke Fatigue (PSF) is a prevalent yet commonly
      neglected issue that impacts daily functions and quality of life in people post
      stroke. To date no studies have attempted to validate a clinically-feasible and
      reliable instrument to quantify PSF. We developed the Visual Analog Fatigue Scale
      (VAFS) to eliminate difficulties and poor data validity in testing people post
      stroke. The purpose of this study was to evaluate the reliability,
      responsiveness, and validity of the VAFS. Methods. Twenty-one people post-stroke
      (12 males, age = 59.5 +/- 10.3 years; time post-stroke = 4.1 +/- 3.5 years)
      participated. Subjects underwent a standardized fatigue-inducing exercise;
      fatigue level was assessed at rest, immediately after exercise, and after
      recovery. The same protocol was repeated after 14 days. Results. ICC values for
      the VAFS at rest was 0.851 (CI = 95%, 0.673 approximately 0.936, P < .001),
      immediately after exercise was 0.846 (CI = 95%, 0.663 approximately 0.934, P <
      .001), and 15 minutes after exercise was 0.888 (CI = 95%, 0.749 approximately
      0.953, P < .001). The ES values for at-rest to post-exercise and for post
      exercise to post-recovery were 14.512 and 0.685, respectively. Using paired t
      test, significant difference was found between VAFS scores at-rest and post
      exercise (P < .001), and between post-exercise and post-recovery (P < .001).
      Conclusion. Our data suggests good reliability, responsiveness, and validity of
      the VAFS to assess exertion fatigue in people post-stroke.

PMID- 20700422
TI  - Stroke status evoked adhesion molecule genetic alterations in astrocytes isolated
      from stroke-prone spontaneously hypertensive rats and the apigenin inhibition of
      their expression.
AB  - We examined the possibility that the expression of adhesion molecules is
      regulated differently in cultured astrocytes from stroke-prone spontaneously
      hypertensive rats (SHRSP/IZM) rats than in those from Wistar Kyoto rats (WKY/IZM)
      by tumor necrosis factor-alpha (TNF-alpha) or hypoxia and reoxygenation (H/R) and
      the inhibitory effects of apigenin. It was found that the expression of vascular
      cell adhesion molecule-1 (VCAM-1) by TNF-alpha in astrocytes isolated from
      SHRSP/IZM was increased compared with that in WKY/IZM. The expression of monocyte
      chemotactic protein-1 (MCP-1) mRNA induced by H/R in SHRSP/IZM astrocytes was
      increased compared with that in normal oxygen concentrations. Apigenin strongly
      attenuated TNF-alpha-induced VCAM-1 mRNA and protein expression and suppressed
      the adhesion of U937 cells and SHRSP/IZM astrocytes. These results suggest that
      the expression levels of adhesion molecules during H/R affect disease outcome and
      can drive SHRSP/IZM to stroke. It is suggested that apigenin regulates adhesion
      molecule expression in reactive astrocytes during ischemia.

PMID- 20700423
TI  - Intracranial vertebrobasilar artery dissection associated with postpartum
      angiopathy.
AB  - Background. Cervicocephalic arterial dissection (CCAD) is rare in the postpartum
      period. To our knowledge this is the first reported case of postpartum angiopathy
      (PPA) presenting with ischemic stroke due to intracranial arterial dissection.
      Case. A 41-year-old woman presented with blurred vision, headache, and
      generalized seizures 5 days after delivering twins. She was treated with
      magnesium for eclampsia. MRI identified multiple posterior circulation infarcts.
      Angiography identified a complex dissection extending from both intradural
      vertebral arteries, through the basilar artery, and into both posterior cerebral
      arteries. Multiple segments of arterial dilatation and narrowing consistent with
      PPA were present. Xenon enhanced CT (Xe-CT) showed reduced regional cerebral
      blood flow that is improved with elevation in blood pressure. Conclusion.
      Intracranial vertebrobasilar dissection causing stroke is a rare complication of
      pregnancy. Eclampsia and PPA may play a role in its pathogenesis. Blood pressure
      management may be tailored using quantitative blood flow studies, such as Xe-CT.

PMID- 20700424
TI  - Applicability of the Filter Paper Technique for Detection of Antifilarial IgG(4)
      Antibodies Using the Bm14 Filariasis CELISA.
AB  - Demonstration of successful elimination of lymphatic filariasis (LF) in endemic
      countries requires sensitive diagnostics for accurate definitions of endpoints
      and future surveillance. There has been interest in complementing available
      diagnostics with antibody serology testing in children, since negative serology
      would correspond with cessation of LF transmission. The Filariasis CELISA detects
      antifilarial IgG(4) and has favourable results with serum samples but field
      application requires an easier sampling method. Ninety-four paired plasma and
      filter paper samples were assayed with promising results. The filter paper method
      resulted in a sensitivity of 92% and a specificity of 77% when compared to the
      paired plasma. One hundred and one filter paper samples were assessed for storage
      effects. Following 10-month storage at -20( degrees )C there was a significant
      reduction in reactivity (P < .001). Overall the results indicated that filter
      paper sampling would be a favourable sensitive and specific alternative for blood
      collection in surveys.

PMID- 20700425
TI  - Evaluation of In Vitro Activity of Essential Oils against Trypanosoma brucei
      brucei and Trypanosoma evansi.
AB  - Essential oils (EOs) from Cymbopogon citratus (CC), Eucalyptus citriodora (EC),
      Eucalyptus camaldulensis (ED), and Citrus sinensis (CS) were obtained by
      hydrodistillation process. The EOs were evaluated in vitro for activity against
      Trypanosoma brucei brucei (Tbb) and Trypanosoma evansi (T. evansi). The EOs were
      found to possess antitrypanosomal activity in vitro in a dose-dependent pattern
      in a short period of time. The drop in number of parasite over time was achieved
      doses of 0.4 g/ml, 0.2 g/mL, and 0.1 g/mL for all the EOs. The concentration of
      0.4 g/mL CC was more potent at 3 minutes and 2 minutes for Tbb and T. evansi,
      respectively. The GC-MS analysis of the EOs revealed presence of Cyclobutane
      (96.09%) in CS, 6-octenal (77.11%) in EC, Eucalyptol (75%) in ED, and Citral
      (38.32%) in CC among several other organic compounds. The results are discussed
      in relation to trypanosome chemotherapy.

PMID- 20700426
TI  - Level of CYP4G19 Expression Is Associated with Pyrethroid Resistance in Blattella
      germanica.
AB  - German cockroaches have become a large problem in the Shenzhen area because of
      their pesticide resistance, especially to pyrethroid. A pyrethroid called "Jia
      Chong Qing" to prevent pests for a long time were found to be resistant to "Jia
      Chong Qing" with resistance index of 3.88 measured using RT-PCR and
      immunohistochemistry analysis showed that both CYP4G19 mRNA and CYP4G19 protein
      expression levels in the wild strain were substantially higher than that of a
      sensitive strain. dsRNA segments derived from the target gene CYP4G19 were
      prepared using in vitro transcription and were microinjected into abdomens of the
      wild strain. Two to eight days after injection, the result showed that CYP4G19
      mRNA expressions were significantly reduced in the groups injected with dsRNAs.

PMID- 20700427
TI  - Effects of Snail Density on Growth, Reproduction and Survival of Biomphalaria
      alexandrina Exposed to Schistosoma mansoni.
AB  - The effects of snail density on Biomphalaria alexandrina parasitized with
      Schistosoma mansoni were investigated. Laboratory experiments were used to
      quantify the impact of high density on snail growth, fecundity, and survival.
      Density-dependent birth rates of snails were determined to inform mathematical
      models, which, until now, have assumed a linear relationship between density and
      fecundity. The experiments show that the rate of egg-laying followed a negative
      exponential distribution with increasing density and this was significantly
      affected by exposure to parasitic infection. High density also affected the
      weight of snails and survival to a greater degree than exposure to parasitic
      infection. Although snail growth rates were initially constrained by high
      density, they retained the potential for growth suggesting a reversible density
      dependent mechanism. These experimental data can be used to parameterise models
      and confirm that snail populations are regulated by nonlinear density-dependent
      mechanisms.

PMID- 20700428
TI  - A cross-sectional survey on parasites of chickens in selected villages in the
      subhumid zones of South-eastern Nigeria.
AB  - A study was carried out to identify and estimate the prevalence of ecto- and
      endoparasites of village chicken between April and July 2008 in three local
      councils of Enugu state, Nigeria. A total of 1038 chickens comprising of 468
      chicks, 207 growers and 363 adults were examined during the house to house survey
      for ectoparasites, gastrointestinal helminths and coccidia infections. Our
      finding showed that 41% were infected with ectoparasites with lice, fleas, and
      mites having prevalence rates of 62.2%, 35.7% and 2.1%, respectively. Helminths
      and coccidia had prevalence of 35.5% each. Among the helminths Ascaridia, galli
      was the most dominant species (17.2%). Generally, there was a significantly
      higher helminth infestation relative to the ectoparasites (P < .05), high
      prevalence of mixed infections and absence of tick infestation. Parasitism could
      be big constraint to production in the study area and we recommend a sustainable
      control strategy.

PMID- 20700429
TI  - Performance of Surgical Stress Index during Sevoflurane-Fentanyl and Isoflurane
      Fentanyl Anesthesia.
AB  - The performance of recently introduced Surgical Stress Index (SSI), based on
      heart rate and photoplethysmography, was estimated during sevoflurane-fentanyl
      and isoflurane-fentanyl anesthesia during surgical procedures. Forty ASA I-III
      patients were enrolled. Anesthesia was induced with fentanyl 2 mug kg(-1) and
      thiopentone 3-5 mg kg(-1). Tracheal intubation was performed 5 minutes after
      fentanyl bolus. Patients were randomly allocated to receive sevoflurane (n = 20)
      or isoflurane (n = 20) in 30% oxygen/air. State entropy was kept at 40-60, target
      being 50. During surgery, fentanyl boluses 1.5 mug kg(-1) were given at 30-40
      minute intervals. SSI increased significantly after intubation. During surgery,
      the decrease of SSI after fentanyl boluses was similar in sevoflurane and
      isoflurane groups but SSI values were higher in sevoflurane than in isoflurane
      group. Tracheal intubation, skin incision, and surgical stimuli increased SSI
      from baseline, indicating that nociceptive stimuli increase SSI. Fentanyl boluses
      during surgery decreased SSI, indicating that increasing analgesia decreases SSI.

PMID- 20700430
TI  - Comparison of the clinical use of macintosh and miller laryngoscopes for
      orotracheal intubation by second-month nurse students in anesthesiology.
AB  - Aim. The aim of this study is to compare the clinical feasibility of Macintosh
      and Miller laryngoscopes for tracheal intubation in non-experienced users in
      anesthetized patients. Patients and Methods. 119 patients were randomized into
      the Macintosh group (59) and the Miller group (60). The primary outcome variable
      was successful tracheal intubation. The secondary outcome variables were number
      of insertion attempt, intubation time needed, total time to intubation,
      hemodynamic change and complications. Results. All patients were successfully
      intubated using the Macintosh, whereas 13 patients (21.6%) were failed with the
      Miller (P < .001). The Macintosh significantly reduced the mean total time to
      intubation (P < .001). There were significant differences in the mean blood
      pressure at 2 minutes after laryngoscope insertion, immediately, and 2 minutes
      after tracheal intubation and in the mean heart rate at the laryngoscope
      insertion, immediately, and at 2 minutes after tracheal intubation between the
      two groups. Overall complications in both were not significantly different.
      Conclusion. Orotracheal intubation using the Macintosh is an effective and safe
      technique in non-experienced hands with significantly increased success rate as
      well as decreased mean total time to intubation as compare to the Miller.
      However, these intubations only apply to selected patients deemed to have normal
      airways.

PMID- 20700431
TI  - Preoperative assessment of adult patients for intracranial surgery.
AB  - The preoperative assessment of the patient for neurosurgical and endovascular
      procedures involves the understanding of the neurological disease and its
      systemic presentation, and the requirements of the procedure. There is a wide
      spectrum of different neurosurgical disorders and procedures. This article
      provides an overview of the preoperative evaluation of these patients with
      respect to general principles of neuroanesthesia, and considerations for specific
      intracranial and vascular neurosurgical and interventional neuroradiological
      procedures.

PMID- 20700432
TI  - Influence of positioning on plain levobupivacaine spinal anesthesia in cesarean
      section.
AB  - Background. The behaviour of isobaric levobupivacaine in relation to gravity when
      used in obstetric spinal anesthesia is unclear. Methods. 46 women with ASA
      physical status 1 undergoing cesarean section were randomly allocated to 2
      groups. Spinal anesthesia with 12.5 mg levobupivacaine was performed in the
      sitting position in all women. Those in the first group were placed in the supine
      position immediately after the injection, while those in the second group were
      asked to remain seated for 2 minutes before assuming the supine position. The
      sensory block level, the onset of sensory and motor blocks, the regression of the
      sensory block for 2 dermatomes of the sensory block, the first request for
      analgesics, and the regression of motor block were recorded. Results. No
      differences in onset times, sensory level, or Bromage score were observed between
      the two groups. The time of first analgesic request was earlier in the seated
      group (supine 131 +/- 42 min, seated 106 +/- 29 min, P = .02). Conclusion.
      Isobaric levobupivacaine in women at term produces a subarachnoid block the
      dermatomal level of which does not depend on gravitational forces.

PMID- 20700433
TI  - Real-time 3-dimensional ultrasound-assisted infraclavicular brachial plexus
      catheter placement: implications of a new technology.
AB  - Background. There are a variety of techniques for targeting placement of an
      infraclavicular blockade; these include eliciting paresthesias, nerve
      stimulation, and 2-dimensional (2D) ultrasound (US) guidance. Current 2D US
      allows direct visualization of a "flat" image of the advancing needle and
      neurovascular structures but without the ability to extensively analyze
      multidimensional data and allow for real-time manipulation. Three-dimensional
      (3D) ultrasonography has gained popularity and usefulness in many clinical
      specialties such as obstetrics and cardiology. We describe some of the potential
      clinical applications of 3D US in regional anesthesia. Methods. This case
      represents an infraclavicular catheter placement facilitated by 3D US, which
      demonstrates 360-degree spatial relationships of the entire anatomic region.
      Results. The block needle, peripheral nerve catheter, and local anesthetic
      diffusion were observed in multiple planes of view without manipulation of the US
      probe. Conclusion. Advantages of 3D US may include the ability to confirm correct
      needle and catheter placement prior to the injection of local anesthetic. The
      spread of local anesthetic along the length of the nerve can be easily observed
      while manipulating the 3D images in real-time by simply rotating the trackball on
      the US machine to provide additional information that cannot be identified with
      2D US alone.

PMID- 20700434
TI  - Multivesicular body formation requires OSBP-related proteins and cholesterol.
AB  - In eukaryotes, different subcellular organelles have distinct cholesterol
      concentrations, which is thought to be critical for biological functions.
      Oxysterol-binding protein-related proteins (ORPs) have been assumed to mediate
      nonvesicular cholesterol trafficking in cells; however, their in vivo functions
      and therefore the biological significance of cholesterol in each organelle are
      not fully understood. Here, by generating deletion mutants of ORPs in
      Caenorhabditis elegans, we show that ORPs are required for the formation and
      function of multivesicular bodies (MVBs). In an RNAi enhancer screen using obr
      quadruple mutants (obr-1; -2; -3; -4), we found that MVB-related genes show
      strong genetic interactions with the obr genes. In obr quadruple mutants, late
      endosomes/lysosomes are enlarged and membrane protein degradation is retarded,
      although endocytosed soluble proteins are normally delivered to lysosomes and
      degraded. We also found that the cholesterol content of late endosomes/lysosomes
      is reduced in the mutants. In wild-type worms, cholesterol restriction induces
      the formation of enlarged late endosomes/lysosomes, as observed in obr quadruple
      mutants, and increases embryonic lethality upon knockdown of MVB-related genes.
      Finally, we show that knockdown of ORP1L, a mammalian ORP family member, induces
      the formation of enlarged MVBs in HeLa cells. Our in vivo findings suggest that
      the proper cholesterol level of late endosomes/lysosomes generated by ORPs is
      required for normal MVB formation and MVB-mediated membrane protein degradation.

PMID- 20700435
TI  - A developmental timing switch promotes axon outgrowth independent of known
      guidance receptors.
AB  - To form functional neuronal connections, axon outgrowth and guidance must be
      tightly regulated across space as well as time. While a number of genes and
      pathways have been shown to control spatial features of axon development, very
      little is known about the in vivo mechanisms that direct the timing of axon
      initiation and elongation. The Caenorhabditis elegans hermaphrodite specific
      motor neurons (HSNs) extend a single axon ventrally and then anteriorly during
      the L4 larval stage. Here we show the lin-4 microRNA promotes HSN axon initiation
      after cell cycle withdrawal. Axons fail to form in lin-4 mutants, while they grow
      prematurely in lin-4-overexpressing animals. lin-4 is required to down-regulate
      two inhibitors of HSN differentiation--the transcriptional regulator LIN-14 and
      the "stemness" factor LIN-28--and it likely does so through a cell-autonomous
      mechanism. This developmental switch depends neither on the UNC-40/DCC and SAX
      3/Robo receptors nor on the direction of axon growth, demonstrating that it acts
      independently of ventral guidance signals to control the timing of HSN axon
      elongation.

PMID- 20700437
TI  - A deviation from the bipolar-tetrapolar mating paradigm in an early diverged
      basidiomycete.
AB  - In fungi, sexual identity is determined by specialized genomic regions called MAT
      loci which are the equivalent to sex chromosomes in some animals and plants.
      Usually, only two sexes or mating types exist, which are determined by two
      alternate sets of genes (or alleles) at the MAT locus (bipolar system). However,
      in the phylum Basidiomycota, a unique tetrapolar system emerged in which four
      different mating types are generated per meiosis. This occurs because two
      functionally distinct molecular recognition systems, each encoded by one MAT
      region, constrain the selection of sexual partners. Heterozygosity at both MAT
      regions is a pre-requisite for mating in both bipolar and tetrapolar
      basidiomycetes. Tetrapolar mating behaviour results from the absence of genetic
      linkage between the two regions bringing forth up to thousands of mating types.
      The subphylum Pucciniomycotina, an early diverged lineage of basidiomycetes
      encompassing important plant pathogens such as the rusts and saprobes like
      Rhodosporidium and Sporidiobolus, has been so far poorly explored concerning the
      content and organization of MAT loci. Here we show that the red yeast
      Sporidiobolus salmonicolor has a mating system unlike any previously described
      because occasional disruptions of the genetic cohesion of the bipolar MAT locus
      originate new mating types. We confirmed that mating is normally bipolar and that
      heterozygosity at both MAT regions is required for mating. However, a laboratory
      cross showed that meiotic recombination may occur within the bipolar MAT locus,
      explaining tetrapolar features like increased allele number and evolution rates
      of some MAT genes. This pseudo-bipolar system deviates from the classical bipolar
      tetrapolar paradigm and, to our knowledge, has never been observed before. We
      propose a model for MAT evolution in the Basidiomycota in which the pseudo
      bipolar system may represent a hitherto unforeseen gradual form of transition
      from an ancestral tetrapolar system to bipolarity.

PMID- 20700436
TI  - Multiple independent loci at chromosome 15q25.1 affect smoking quantity: a meta
      analysis and comparison with lung cancer and COPD.
AB  - Recently, genetic association findings for nicotine dependence, smoking behavior,
      and smoking-related diseases converged to implicate the chromosome 15q25.1
      region, which includes the CHRNA5-CHRNA3-CHRNB4 cholinergic nicotinic receptor
      subunit genes. In particular, association with the nonsynonymous CHRNA5 SNP
      rs16969968 and correlates has been replicated in several independent studies.
      Extensive genotyping of this region has suggested additional statistically
      distinct signals for nicotine dependence, tagged by rs578776 and rs588765. One
      goal of the Consortium for the Genetic Analysis of Smoking Phenotypes (CGASP) is
      to elucidate the associations among these markers and dichotomous smoking
      quantity (heavy versus light smoking), lung cancer, and chronic obstructive
      pulmonary disease (COPD). We performed a meta-analysis across 34 datasets of
      European-ancestry subjects, including 38,617 smokers who were assessed for
      cigarettes-per-day, 7,700 lung cancer cases and 5,914 lung-cancer-free controls
      (all smokers), and 2,614 COPD cases and 3,568 COPD-free controls (all smokers).
      We demonstrate statistically independent associations of rs16969968 and rs588765
      with smoking (mutually adjusted p-values<10(-35) and <10(-8) respectively).
      Because the risk alleles at these loci are negatively correlated, their
      association with smoking is stronger in the joint model than when each SNP is
      analyzed alone. Rs578776 also demonstrates association with smoking after
      adjustment for rs16969968 (p<10(-6)). In models adjusting for cigarettes-per-day,
      we confirm the association between rs16969968 and lung cancer (p<10(-20)) and
      observe a nominally significant association with COPD (p = 0.01); the other loci
      are not significantly associated with either lung cancer or COPD after adjusting
      for rs16969968. This study provides strong evidence that multiple statistically
      distinct loci in this region affect smoking behavior. This study is also the
      first report of association between rs588765 (and correlates) and smoking that
      achieves genome-wide significance; these SNPs have previously been associated
      with mRNA levels of CHRNA5 in brain and lung tissue.

PMID- 20700438
TI  - The 5p15.33 locus is associated with risk of lung adenocarcinoma in never-smoking
      females in Asia.
AB  - Genome-wide association studies of lung cancer reported in populations of
      European background have identified three regions on chromosomes 5p15.33,
      6p21.33, and 15q25 that have achieved genome-wide significance with p-values of
      10(-7) or lower. These studies have been performed primarily in cigarette
      smokers, raising the possibility that the observed associations could be related
      to tobacco use, lung carcinogenesis, or both. Since most women in Asia do not
      smoke, we conducted a genome-wide association study of lung adenocarcinoma in
      never-smoking females (584 cases, 585 controls) among Han Chinese in Taiwan and
      found that the most significant association was for rs2736100 on chromosome
      5p15.33 (p = 1.30 x 10(-11)). This finding was independently replicated in seven
      studies from East Asia totaling 1,164 lung adenocarcinomas and 1,736 controls (p
      = 5.38 x 10(-11)). A pooled analysis achieved genome-wide significance for
      rs2736100. This SNP marker localizes to the CLPTM1L-TERT locus on chromosome
      5p15.33 (p = 2.60 x 10(-20), allelic risk = 1.54, 95% Confidence Interval (CI)
      1.41-1.68). Risks for heterozygote and homozygote carriers of the minor allele
      were 1.62 (95% CI; 1.40-1.87), and 2.35 (95% CI: 1.95-2.83), respectively. In
      summary, our results show that genetic variation in the CLPTM1L-TERT locus of
      chromosome 5p15.33 is directly associated with the risk of lung cancer, most
      notably adenocarcinoma.

PMID- 20700439
TI  - The extinction dynamics of bacterial pseudogenes.
AB  - Pseudogenes are usually considered to be completely neutral sequences whose
      evolution is shaped by random mutations and chance events. It is possible,
      however, for disrupted genes to generate products that are deleterious due either
      to the energetic costs of their transcription and translation or to the formation
      of toxic proteins. We found that after their initial formation, the youngest
      pseudogenes in Salmonella genomes have a very high likelihood of being removed by
      deletional processes and are eliminated too rapidly to be governed by a strictly
      neutral model of stochastic loss. Those few highly degraded pseudogenes that have
      persisted in Salmonella genomes correspond to genes with low expression levels
      and low connectivity in gene networks, such that their inactivation and any
      initial deleterious effects associated with their inactivation are buffered.
      Although pseudogenes have long been considered the paradigm of neutral evolution,
      the distribution of pseudogenes among Salmonella strains indicates that removal
      of many of these apparently functionless regions is attributable to positive
      selection.

PMID- 20700440
TI  - RNAi screening implicates a SKN-1-dependent transcriptional response in stress
      resistance and longevity deriving from translation inhibition.
AB  - Caenorhabditis elegans SKN-1 (ortholog of mammalian Nrf1/2/3) is critical for
      oxidative stress resistance and promotes longevity under reduced insulin/IGF-1
      like signaling (IIS), dietary restriction (DR), and normal conditions. SKN-1
      inducibly activates genes involved in detoxification, protein homeostasis, and
      other functions in response to stress. Here we used genome-scale RNA interference
      (RNAi) screening to identify mechanisms that prevent inappropriate SKN-1 target
      gene expression under non-stressed conditions. We identified 41 genes for which
      knockdown leads to activation of a SKN-1 target gene (gcs-1) through skn-1
      dependent or other mechanisms. These genes correspond to multiple cellular
      processes, including mRNA translation. Inhibition of translation is known to
      increase longevity and stress resistance and may be important for DR-induced
      lifespan extension. One model postulates that these effects derive from reduced
      energy needs, but various observations suggest that specific longevity pathways
      are involved. Here we show that translation initiation factor RNAi robustly
      induces SKN-1 target gene transcription and confers skn-1-dependent oxidative
      stress resistance. The accompanying increases in longevity are mediated largely
      through the activities of SKN-1 and the transcription factor DAF-16 (FOXO), which
      is required for longevity that derives from reduced IIS. Our results indicate
      that the SKN-1 detoxification gene network monitors various metabolic and
      regulatory processes. Interference with one of these processes, translation
      initiation, leads to a transcriptional response whereby SKN-1 promotes stress
      resistance and functions together with DAF-16 to extend lifespan. This stress
      response may be beneficial for coping with situations that are associated with
      reduced protein synthesis.

PMID- 20700441
TI  - Dynamics of Rad9 chromatin binding and checkpoint function are mediated by its
      dimerization and are cell cycle-regulated by CDK1 activity.
AB  - Saccharomyces cerevisiae Rad9 is required for an effective DNA damage response
      throughout the cell cycle. Assembly of Rad9 on chromatin after DNA damage is
      promoted by histone modifications that create docking sites for Rad9 recruitment,
      allowing checkpoint activation. Rad53 phosphorylation is also dependent upon BRCT
      directed Rad9 oligomerization; however, the crosstalk between these molecular
      determinants and their functional significance are poorly understood. Here we
      report that, in the G1 and M phases of the cell cycle, both constitutive and DNA
      damage-dependent Rad9 chromatin association require its BRCT domains. In G1
      cells, GST or FKBP dimerization motifs can substitute to the BRCT domains for
      Rad9 chromatin binding and checkpoint function. Conversely, forced Rad9
      dimerization in M phase fails to promote its recruitment onto DNA, although it
      supports Rad9 checkpoint function. In fact, a parallel pathway, independent on
      histone modifications and governed by CDK1 activity, allows checkpoint activation
      in the absence of Rad9 chromatin binding. CDK1-dependent phosphorylation of Rad9
      on Ser11 leads to specific interaction with Dpb11, allowing Rad53 activation and
      bypassing the requirement for the histone branch.

PMID- 20700442
TI  - A missense mutation in a highly conserved alternate exon of dynamin-1 causes
      epilepsy in fitful mice.
AB  - Dynamin-1 (Dnm1) encodes a large multimeric GTPase necessary for activity
      dependent membrane recycling in neurons, including synaptic vesicle endocytosis.
      Mice heterozygous for a novel spontaneous Dnm1 mutation--fitful--experience
      recurrent seizures, and homozygotes have more debilitating, often lethal seizures
      in addition to severe ataxia and neurosensory deficits. Fitful is a missense
      mutation in an exon that defines the DNM1a isoform, leaving intact the
      alternatively spliced exon that encodes DNM1b. The expression of the
      corresponding alternate transcripts is developmentally regulated, with DNM1b
      expression highest during early neuronal development and DNM1a expression
      increasing postnatally with synaptic maturation. Mutant DNM1a does not
      efficiently self-assemble into higher order complexes known to be necessary for
      proper dynamin function, and it also interferes with endocytic recycling in cell
      culture. In mice, the mutation results in defective synaptic transmission
      characterized by a slower recovery from depression after trains of stimulation.
      The DNM1a and DNM1b isoform pair is highly conserved in vertebrate evolution,
      whereas invertebrates have only one isoform. We speculate that the emergence of
      more specialized forms of DNM1 may be important in organisms with complex
      neuronal function.

PMID- 20700444
TI  - Spliced leader trapping reveals widespread alternative splicing patterns in the
      highly dynamic transcriptome of Trypanosoma brucei.
AB  - Trans-splicing of leader sequences onto the 5'ends of mRNAs is a widespread
      phenomenon in protozoa, nematodes and some chordates. Using parallel sequencing
      we have developed a method to simultaneously map 5'splice sites and analyze the
      corresponding gene expression profile, that we term spliced leader trapping
      (SLT). The method can be applied to any organism with a sequenced genome and
      trans-splicing of a conserved leader sequence. We analyzed the expression
      profiles and splicing patterns of bloodstream and insect forms of the parasite
      Trypanosoma brucei. We detected the 5' splice sites of 85% of the annotated
      protein-coding genes and, contrary to previous reports, found up to 40% of
      transcripts to be differentially expressed. Furthermore, we discovered more than
      2500 alternative splicing events, many of which appear to be stage-regulated.
      Based on our findings we hypothesize that alternatively spliced transcripts
      present a new means of regulating gene expression and could potentially
      contribute to protein diversity in the parasite. The entire dataset can be
      accessed online at TriTrypDB or through: http://splicer.unibe.ch/.

PMID- 20700443
TI  - Genome-wide association studies of serum magnesium, potassium, and sodium
      concentrations identify six Loci influencing serum magnesium levels.
AB  - Magnesium, potassium, and sodium, cations commonly measured in serum, are
      involved in many physiological processes including energy metabolism, nerve and
      muscle function, signal transduction, and fluid and blood pressure regulation. To
      evaluate the contribution of common genetic variation to normal physiologic
      variation in serum concentrations of these cations, we conducted genome-wide
      association studies of serum magnesium, potassium, and sodium concentrations
      using approximately 2.5 million genotyped and imputed common single nucleotide
      polymorphisms (SNPs) in 15,366 participants of European descent from the
      international CHARGE Consortium. Study-specific results were combined using fixed
      effects inverse-variance weighted meta-analysis. SNPs demonstrating genome-wide
      significant (p<5 x 10(-8)) or suggestive associations (p<4 x 10(-7)) were
      evaluated for replication in an additional 8,463 subjects of European descent.
      The association of common variants at six genomic regions (in or near MUC1,
      ATP2B1, DCDC5, TRPM6, SHROOM3, and MDS1) with serum magnesium levels was genome
      wide significant when meta-analyzed with the replication dataset. All initially
      significant SNPs from the CHARGE Consortium showed nominal association with
      clinically defined hypomagnesemia, two showed association with kidney function,
      two with bone mineral density, and one of these also associated with fasting
      glucose levels. Common variants in CNNM2, a magnesium transporter studied only in
      model systems to date, as well as in CNNM3 and CNNM4, were also associated with
      magnesium concentrations in this study. We observed no associations with serum
      sodium or potassium levels exceeding p<4 x 10(-7). Follow-up studies of newly
      implicated genomic loci may provide additional insights into the regulation and
      homeostasis of human serum magnesium levels.

PMID- 20700445
TI  - Contribution of coagulases towards Staphylococcus aureus disease and protective
      immunity.
AB  - The bacterial pathogen Staphylococcus aureus seeds abscesses in host tissues to
      replicate at the center of these lesions, protected from host immune cells via a
      pseudocapsule. Using histochemical staining, we identified prothrombin and fibrin
      within abscesses and pseudocapsules. S. aureus secretes two clotting factors,
      coagulase (Coa) and von Willebrand factor binding protein (vWbp). We report here
      that Coa and vWbp together are required for the formation of abscesses. Coa and
      vWbp promote the non-proteolytic activation of prothrombin and cleavage of
      fibrinogen, reactions that are inhibited with specific antibody against each of
      these molecules. Coa and vWbp specific antibodies confer protection against
      abscess formation and S. aureus lethal bacteremia, suggesting that coagulases
      function as protective antigens for a staphylococcal vaccine.

PMID- 20700446
TI  - The transcription factor Rbf1 is the master regulator for b-mating type
      controlled pathogenic development in Ustilago maydis.
AB  - In the phytopathogenic basidiomycete Ustilago maydis, sexual and pathogenic
      development are tightly connected and controlled by the heterodimeric bE/bW
      transcription factor complex encoded by the b-mating type locus. The formation of
      the active bE/bW heterodimer leads to the formation of filaments, induces a G2
      cell cycle arrest, and triggers pathogenicity. Here, we identify a set of 345
      bE/bW responsive genes which show altered expression during these developmental
      changes; several of these genes are associated with cell cycle coordination,
      morphogenesis and pathogenicity. 90% of the genes that show altered expression
      upon bE/bW-activation require the zinc finger transcription factor Rbf1, one of
      the few factors directly regulated by the bE/bW heterodimer. Rbf1 is a novel
      master regulator in a multilayered network of transcription factors that
      facilitates the complex regulatory traits of sexual and pathogenic development.

PMID- 20700447
TI  - Biological and structural characterization of a host-adapting amino acid in
      influenza virus.
AB  - Two amino acids (lysine at position 627 or asparagine at position 701) in the
      polymerase subunit PB2 protein are considered critical for the adaptation of
      avian influenza A viruses to mammals. However, the recently emerged pandemic H1N1
      viruses lack these amino acids. Here, we report that a basic amino acid at
      position 591 of PB2 can compensate for the lack of lysine at position 627 and
      confers efficient viral replication to pandemic H1N1 viruses in mammals.
      Moreover, a basic amino acid at position 591 of PB2 substantially increased the
      lethality of an avian H5N1 virus in mice. We also present the X-ray
      crystallographic structure of the C-terminus of a pandemic H1N1 virus PB2
      protein. Arginine at position 591 fills the cleft found in H5N1 PB2 proteins in
      this area, resulting in differences in surface shape and charge for H1N1 PB2
      proteins. These differences may affect the protein's interaction with viral
      and/or cellular factors, and hence its ability to support virus replication in
      mammals.

PMID- 20700448
TI  - Bim nuclear translocation and inactivation by viral interferon regulatory factor.
AB  - Viral replication efficiency is in large part governed by the ability of viruses
      to counteract pro-apoptotic signals induced by infection of the host cell. Human
      herpesvirus 8 (HHV-8) uses several strategies to block the host's innate
      antiviral defenses via interference with interferon and apoptotic signaling.
      Contributors include the four viral interferon regulatory factors (vIRFs 1-4),
      which function in dominant negative fashion to block cellular IRF activities in
      addition to targeting IRF signaling-induced proteins such as p53 and inhibiting
      other inducers of apoptosis such as TGFbeta receptor-activated Smad transcription
      factors. Here we identify direct targeting by vIRF-1 of BH3-only pro-apoptotic
      Bcl-2 family member Bim, a key negative regulator of HHV-8 replication, to effect
      its inactivation via nuclear translocation. vIRF-1-mediated relocalization of Bim
      was identified in transfected cells, by both immunofluorescence assay and western
      analysis of fractionated cell extracts. Also, co-localization of vIRF-1 and Bim
      was detected in nuclei of lytically infected endothelial cells. In vitro co
      precipitation assays using purified vIRF-1 and Bim revealed direct interaction
      between the proteins, and Bim-binding residues of vIRF-1 were mapped by deletion
      and point mutagenesis. Generation and experimental utilization of Bim-refractory
      vIRF-1 variants revealed the importance of vIRF-1:Bim interaction, specifically,
      in pro-replication and anti-apoptotic activity of vIRF-1. Furthermore, blocking
      of the interaction with cell-permeable peptide corresponding to the Bim-binding
      region of vIRF-1 confirmed the relevance of vIRF-1:Bim association to vIRF-1 pro
      replication activity. To our knowledge, this is the first report of an IRF
      protein that interacts with a Bcl-2 family member and of nuclear sequestration of
      Bim or any other member of the family as a means of inactivation. The data
      presented reveal a novel mechanism utilized by a virus to control replication
      induced apoptosis and suggest that inhibitory targeting of vIRF-1:Bim interaction
      may provide an effective antiviral strategy.

PMID- 20700449
TI  - A limited number of antibody specificities mediate broad and potent serum
      neutralization in selected HIV-1 infected individuals.
AB  - A protective vaccine against HIV-1 will likely require the elicitation of a
      broadly neutralizing antibody (bNAb) response. Although the development of an
      immunogen that elicits such antibodies remains elusive, a proportion of HIV-1
      infected individuals evolve broadly neutralizing serum responses over time,
      demonstrating that the human immune system can recognize and generate NAbs to
      conserved epitopes on the virus. Understanding the specificities that mediate
      broad neutralization will provide insight into which epitopes should be targeted
      for immunogen design and aid in the isolation of broadly neutralizing monoclonal
      antibodies from these donors. Here, we have used a number of new and established
      technologies to map the bNAb specificities in the sera of 19 donors who exhibit
      among the most potent cross-clade serum neutralizing activities observed to date.
      The results suggest that broad and potent serum neutralization arises in most
      donors through a limited number of specificities (1-2 per donor). The major
      targets recognized are an epitope defined by the bNAbs PG9 and PG16 that is
      associated with conserved regions of the V1, V2 and V3 loops, an epitope
      overlapping the CD4 binding site and possibly the coreceptor binding site, an
      epitope sensitive to a loss of the glycan at N332 and distinct from that
      recognized by the bNAb 2G12 and an epitope sensitive to an I165A substitution. In
      approximately half of the donors, key N-linked glycans were critical for
      expression of the epitopes recognized by the bNAb specificities in the sera.

PMID- 20700450
TI  - Dissecting the genetic architecture of host-pathogen specificity.

PMID- 20700452
TI  - Correction: The role of coupled positive feedback in the expression of the SPI1
      type three secretion system in Salmonella.
AB  - Salmonella enterica serovar Typhimurium is a common food-borne pathogen that
      induces inflammatory diarrhea and invades intestinal epithelial cells using a
      type three secretion system (T3SS) encoded within Salmonella pathogenicity island
      1 (SPI1). The genes encoding the SPI1 T3SS are tightly regulated by a network of
      interacting transcriptional regulators involving three coupled positive feedback
      loops. While the core architecture of the SPI1 gene circuit has been determined,
      the relative roles of these interacting regulators and associated feedback loops
      are still unknown. To determine the function of this circuit, we measured gene
      expression dynamics at both population and single-cell resolution in a number of
      SPI1 regulatory mutants. Using these data, we constructed a mathematical model of
      the SPI1 gene circuit. Analysis of the model predicted that the circuit serves
      two functions. The first is to place a threshold on SPI1 activation, ensuring
      that the genes encoding the T3SS are expressed only in response to the
      appropriate combination of environmental and cellular cues. The second is to
      amplify SPI1 gene expression. To experimentally test these predictions, we
      rewired the SPI1 genetic circuit by changing its regulatory architecture. This
      enabled us to directly test our predictions regarding the function of the circuit
      by varying the strength and dynamics of the activating signal. Collectively, our
      experimental and computational results enable us to deconstruct this complex
      circuit and determine the role of its individual components in regulating SPI1
      gene expression dynamics.

PMID- 20700451
TI  - Insecticide control of vector-borne diseases: when is insecticide resistance a
      problem?
AB  - Many of the most dangerous human diseases are transmitted by insect vectors.
      After decades of repeated insecticide use, all of these vector species have
      demonstrated the capacity to evolve resistance to insecticides. Insecticide
      resistance is generally considered to undermine control of vector-transmitted
      diseases because it increases the number of vectors that survive the insecticide
      treatment. Disease control failure, however, need not follow from vector control
      failure. Here, we review evidence that insecticide resistance may have an impact
      on the quality of vectors and, specifically, on three key determinants of
      parasite transmission: vector longevity, competence, and behaviour. We argue
      that, in some instances, insecticide resistance is likely to result in a decrease
      in vector longevity, a decrease in infectiousness, or in a change in behaviour,
      all of which will reduce the vectorial capacity of the insect. If this effect is
      sufficiently large, the impact of insecticide resistance on disease management
      may not be as detrimental as previously thought. In other instances, however,
      insecticide resistance may have the opposite effect, increasing the insect's
      vectorial capacity, which may lead to a dramatic increase in the transmission of
      the disease and even to a higher prevalence than in the absence of insecticides.
      Either way-and there may be no simple generality-the consequence of the evolution
      of insecticide resistance for disease ecology deserves additional attention.

PMID- 20700453
TI  - High-throughput SuperSAGE for digital gene expression analysis of multiple
      samples using next generation sequencing.
AB  - We established a protocol of the SuperSAGE technology combined with next
      generation sequencing, coined "High-Throughput (HT-) SuperSAGE". SuperSAGE is a
      method of digital gene expression profiling that allows isolation of 26-bp tag
      fragments from expressed transcripts. In the present protocol, index (barcode)
      sequences are employed to discriminate tags from different samples. Such barcodes
      allow researchers to analyze digital tags from transcriptomes of many samples in
      a single sequencing run by simply pooling the libraries. Here, we demonstrated
      that HT-SuperSAGE provided highly sensitive, reproducible and accurate digital
      gene expression data. By increasing throughput for analysis in HT-SuperSAGE,
      various applications are foreseen and several examples are provided in the
      present study, including analyses of laser-microdissected cells, biological
      replicates and tag extraction using different anchoring enzymes.

PMID- 20700454
TI  - Lentiviral vector delivery of human interleukin-7 (hIL-7) to human immune system
      (HIS) mice expands T lymphocyte populations.
AB  - Genetically modified mice carrying engrafted human tissues provide useful models
      to study human cell biology in physiologically relevant contexts. However, there
      remain several obstacles limiting the compatibility of human cells within their
      mouse hosts. Among these is inadequate cross-reactvitiy between certain mouse
      cytokines and human cellular receptors, depriving the graft of important survival
      and growth signals. To circumvent this problem, we utilized a lentivirus-based
      delivery system to express physiologically relevant levels of human interleukin-7
      (hIL-7) in Rag2-/-gammac-/- mice following a single intravenous injection. hIL-7
      promoted homeostatic proliferation of both adoptively transferred and
      endogenously generated T-cells in Rag2-/-gammac-/- Human Immune System (HIS)
      mice. Interestingly, we found that hIL-7 increased T lymphocyte numbers in the
      spleens of HIV infected HIS mice without affecting viral load. Taken together,
      our study unveils a versatile approach to deliver human cytokines to HIS mice, to
      both improve engraftment and determine the impact of cytokines on human diseases.

PMID- 20700455
TI  - Hirsch index and truth survival in clinical research.
AB  - BACKGROUND: Factors associated with the survival of truth of clinical conclusions
      in the medical literature are unknown. We hypothesized that publications with a
      first author having a higher Hirsch' index value (h-I), which quantifies and
      predicts an individual's scientific research output, should have a longer half
      life. METHODS AND RESULTS: 474 original articles concerning cirrhosis or
      hepatitis published from 1945 to 1999 were selected. The survivals of the main
      conclusions were updated in 2009. The truth survival was assessed by time
      dependent methods (Kaplan Meier method and Cox). A conclusion was considered to
      be true, obsolete or false when three or more observers out of the six stated it
      to be so. 284 out of 474 conclusions (60%) were still considered true, 90 (19%)
      were considered obsolete and 100 (21%) false. The median of the h-I was=24 (range
      1-85). Authors with true conclusions had significantly higher h-I (median=28)
      than those with obsolete (h-I=19; P=0.002) or false conclusions (h-I=19; P=0.01).
      The factors associated (P<0.0001) with h-I were: scientific life (h-I=33 for>30
      years vs. 16 for<30 years), -methodological quality score (h-I=36 for high vs. 20
      for low scores), and -positive predictive value combining power, ratio of true to
      not-true relationships and bias (h-I=33 for high vs. 20 for low values). In
      multivariate analysis, the risk ratio of h-I was 1.003 (95%CI, 0.994-1.011), and
      was not significant (P=0.56). In a subgroup restricted to 111 articles with a
      negative conclusion, we observed a significant independent prognostic value of h
      I (risk ratio=1.033; 95%CI, 1.008-1.059; P=0.009). Using an extrapolation of h-I
      at the time of article publication there was a significant and independent
      prognostic value of baseline h-I (risk ratio=0.027; P=0.0001). CONCLUSIONS: The
      present study failed to clearly demonstrate that the h-index of authors was a
      prognostic factor for truth survival. However the h-index was associated with
      true conclusions, methodological quality of trials and positive predictive
      values.

PMID- 20700456
TI  - The human proteins MBD5 and MBD6 associate with heterochromatin but they do not
      bind methylated DNA.
AB  - BACKGROUND: MBD5 and MBD6 are two uncharacterized mammalian proteins that contain
      a putative Methyl-Binding Domain (MBD). In the proteins MBD1, MBD2, MBD4, and
      MeCP2, this domain allows the specific recognition of DNA containing methylated
      cytosine; as a consequence, the proteins serve as interpreters of DNA
      methylation, an essential epigenetic mark. It is unknown whether MBD5 or MBD6
      also bind methylated DNA; this question has interest for basic research, but also
      practical consequences for human health, as MBD5 deletions are the likely cause
      of certain cases of mental retardation. PRINCIPAL FINDINGS: Here we report the
      first functional characterization of MBD5 and MBD6. We have observed that the
      proteins colocalize with heterochromatin in cultured cells, and that this
      localization requires the integrity of their MBD. However, heterochromatic
      localization is maintained in cells with severely decreased levels of DNA
      methylation. In vitro, neither MBD5 nor MBD6 binds any of the methylated
      sequences DNA that were tested. CONCLUSIONS: Our data suggest that MBD5 and MBD6
      are unlikely to be methyl-binding proteins, yet they may contribute to the
      formation or function of heterochromatin. One isoform of MBD5 is highly expressed
      in oocytes, which suggests a possible role in epigenetic reprogramming after
      fertilization.

PMID- 20700457
TI  - Decreasing burden of malaria in pregnancy in Malawian women and its relationship
      to use of intermittent preventive therapy or bed nets.
AB  - BACKGROUND: The World Health Organization recommends insecticidal bednets and
      intermittent preventive treatment to reduce malaria in pregnancy. Longitudinal
      data of malaria prevalence and pregnancy outcomes are valuable in gauging the
      impact of these antimalarial interventions. METHODOLOGY/PRINCIPAL FINDINGS: We
      recruited 8,131 women delivering in a single Malawian hospital over 9 years. We
      recorded demographic data, antenatal prescription of intermittent preventive
      therapy during pregnancy with sulfadoxine-pyrimethamine and bed net use, and
      examined finger-prick blood for malaria parasites and hemoglobin concentration.
      In 4,712 women, we examined placental blood for malaria parasites and recorded
      the infant's birth weight. Peripheral and placental parasitemia prevalence
      declined from 23.5% to 5.0% and from 25.2% to 6.8% respectively. Smaller declines
      in prevalence of low birth weight and anemia were observed. Coverage of
      intermittent preventive treatment and bednets increased. Number of sulfadoxine
      pyrimethamine doses received correlated inversely with placental parasitemia
      (Odds Ratio (95% CI): 0.79 (0.68, 0.91)), maternal anemia (0.81, (0.73, 0.90))
      and low birth weight from 1997-2001 (0.63 (0.53, 0.75)), but not from 2002-2006.
      Bednet use protected from peripheral parasitemia (0.47, (0.37, 0.60)) and
      placental parasitemia (0.41, (0.31, 0.54)) and low birth weight (0.75 (0.59,
      0.95)) but not anemia throughout the study. Compared to women without nets who
      did not receive 2-dose sulfadoxine-pyrimethamine, women using nets and receiving
      2-dose sulfadoxine-pyrimethamine were less likely to have parasitemia or low
      birth weight babies. Women receiving 2-dose sulfadoxine-pyrimethamine alone had
      little evidence of protection whereas bednets alone gave intermediate protection.
      CONCLUSIONS/SIGNIFICANCE: Increased bednet coverage explains changes in
      parasitemia and birth weight among pregnant women better than sulfadoxine
      pyrimethamine use. High bed net coverage, and sulfadoxine-pyrimethamine
      resistance, may be contributing to its apparent loss of effectiveness.

PMID- 20700458
TI  - Electrophysiological characteristics of globus pallidus neurons.
AB  - Extracellular recordings in primates have identified two types of neurons in the
      external segment of the globus pallidus (GPE): high frequency pausers (HFP) and
      low frequency bursters (LFB). The aim of the current study was to test whether
      the properties of HFP and LFB neurons recorded extracellularly in the primate GPe
      are linked to cellular mechanisms underlying the generation of action potential
      (AP) firing. Thus, we recorded from primate and rat globus pallidus neurons.
      Extracellular recordings in primates revealed that in addition to differences in
      firing patterns the APs of neurons in these two groups have different widths
      (APex). To quantitatively investigate this difference and to explore the
      heterogeneity of pallidal neurons we carried out cell-attached and whole-cell
      recordings from acute slices of the rat globus pallidus (GP, the rodent homolog
      of the primate GPe), examining both spontaneous and evoked activity. Several
      parameters related to the extracellular activity were extracted in order to
      subdivide the population of recorded GP neurons into groups. Statistical analysis
      showed that the GP neurons in the rodents may be differentiated along six
      cellular parameters into three subgroups. Combining two of these groups allowed a
      better separation of the population along nine parameters. Four of these
      parameters (Fmax, APamp, APhw, and AHPs amplitude) form a subset, suggesting that
      one group of neurons may generate APs at significantly higher frequencies than
      the other group. This may suggest that the differences between the HFP and LFB
      neurons in the primate are related to fundamental underlying differences in their
      cellular properties.

PMID- 20700459
TI  - Imaging beta-galactosidase activity in human tumor xenografts and transgenic mice
      using a chemiluminescent substrate.
AB  - BACKGROUND: Detection of enzyme activity or transgene expression offers potential
      insight into developmental biology, disease progression, and potentially
      personalized medicine. Historically, the lacZ gene encoding the enzyme beta
      galactosidase has been the most common reporter gene and many chromogenic and
      fluorogenic substrates are well established, but limited to histology or in vitro
      assays. We now present a novel approach for in vivo detection of beta
      galactosidase using optical imaging to detect light emission following
      administration of the chemiluminescent 1,2-dioxetane substrate Galacto-Light
      PlusTM. METHODOLOGY AND PRINCIPAL FINDINGS: B-gal activity was visualized in
      stably transfected human MCF7-lacZ tumors growing in mice. LacZ tumors were
      identified versus contralateral wild type tumors as controls, based on two- to
      tenfold greater light emission following direct intra tumoral or intravenous
      administration of reporter substrate. The 1,2-dioxetane substrate is commercially
      available as a kit for microplate-based assays for beta-gal detection, and we
      have adapted it for in vivo application. Typically, 100 microl substrate mixture
      was administered intravenously and light emission was detected from the lacZ
      tumor immediately with gradual decrease over the next 20 mins. Imaging was also
      undertaken in transgenic ROSA26 mice following subcutaneous or intravenous
      injection of substrate mixture. CONCLUSION AND SIGNIFICANCE: Light emission was
      detectable using standard instrumentation designed for more traditional
      bioluminescent imaging. Use of 1,2-dioxetane substrates to detect enzyme activity
      offers a new paradigm for non-invasive biochemistry in vivo.

PMID- 20700460
TI  - Bottlenecks for high coverage of intermittent preventive treatment in pregnancy:
      the case of adolescent pregnancies in rural Burkina Faso.
AB  - BACKGROUND: While IPTp-SP is currently being scaled up in sub-Saharan Africa
      (SSA), the coverage with the required>or=2 doses of SP remains considerably short
      of the Roll Back Malaria (RBM) goal of 80%, not to mention of the recently
      advocated universal coverage. METHODS: The study triangulates quantitative data
      from a health center randomized community-based trial on IPTp-SP effectiveness
      and the additional benefit of a promotional campaign with qualitative data from
      focused ethnography. FINDINGS: In rural Burkina Faso, despite the significantly
      higher risk of malaria infection among adolescent primigravidae (PG) (OR 2.44
      95%CI 1.81-3.28, p<0.001), making them primary target beneficiaries of IPTp-SP,
      adolescents adhered to the required three or more ANC visits significantly less
      (PG: 46.6%; SG 43.7%) than adults (PG: 61.9%; SG 54.9%) and had lower SP uptake
      during the malaria transmission season, further showing the difficulty of
      reaching this age group. Adolescents' structural constraints (such as their
      social position and household labor requirements) and needs (such as anonymity in
      the health encounter) leave them highly vulnerable during their pregnancies and,
      especially, during the high malaria transmission season. CONCLUSION: Our study
      shows that adolescents need to be targeted specifically, prior to their first
      pregnancy and with measures adapted to their social context, addressing their
      structural constraints and needs and going beyond standard health promotion
      campaigns. Unless such specific measures are taken, adolescents' social
      vulnerability will present a serious bottleneck for the effectiveness of IPTi-SP.

PMID- 20700461
TI  - Women have higher protein content of beta-oxidation enzymes in skeletal muscle
      than men.
AB  - It is well recognized that compared with men, women have better ultra-endurance
      capacity, oxidize more fat during endurance exercise, and are more resistant to
      fat oxidation defects i.e. diet-induced insulin resistance. Several groups have
      shown that the mRNA and protein transcribed and translated from genes related to
      transport of fatty acids into the muscle are greater in women than men; however,
      the mechanism(s) for the observed sex differences in fat oxidation remains to be
      determined. Muscle biopsies from the vastus lateralis were obtained from
      moderately active men (N=12) and women (N=11) at rest to examine mRNA and protein
      content of genes involved in lipid oxidation. Our results show that women have
      significantly higher protein content for tri-functional protein alpha (TFPalpha),
      very long chain acyl-CoA dehydrogenase (VLCAD), and medium chain acyl-CoA
      dehydrogenase (MCAD) (P<0.05). There was no significant sex difference in the
      expression of short-chain hydroxyacyl-CoA dehydrogenase (SCHAD), or peroxisome
      proliferator activated receptor alpha (PPARalpha), or PPARgamma, genes
      potentially involved in the transcriptional regulation of lipid metabolism. In
      conclusion, women have more protein content of the major enzymes involved in long
      and medium chain fatty acid oxidation which could account for the observed
      differences in fat oxidation during exercise.

PMID- 20700462
TI  - Evidence for sub-haplogroup h5 of mitochondrial DNA as a risk factor for late
      onset Alzheimer's disease.
AB  - BACKGROUND: Alzheimer's Disease (AD) is the most common neurodegenerative disease
      and the leading cause of dementia among senile subjects. It has been proposed
      that AD can be caused by defects in mitochondrial oxidative phosphorylation.
      Given the fundamental contribution of the mitochondrial genome (mtDNA) for the
      respiratory chain, there have been a number of studies investigating the
      association between mtDNA inherited variants and multifactorial diseases, however
      no general consensus has been reached yet on the correlation between mtDNA
      haplogroups and AD. METHODOLOGY/PRINCIPAL FINDINGS: We applied for the first time
      a high resolution analysis (sequencing of displacement loop and restriction
      analysis of specific markers in the coding region of mtDNA) to investigate the
      possible association between mtDNA-inherited sequence variation and AD in 936 AD
      patients and 776 cognitively assessed normal controls from central and northern
      Italy. Among over 40 mtDNA sub-haplogroups analysed, we found that sub-haplogroup
      H5 is a risk factor for AD (OR=1.85, 95% CI:1.04-3.23) in particular for females
      (OR=2.19, 95% CI:1.06-4.51) and independently from the APOE genotype.
      Multivariate logistic regression revealed an interaction between H5 and age. When
      the whole sample is considered, the H5a subgroup of molecules, harboring the 4336
      transition in the tRNAGln gene, already associated to AD in early studies, was
      about threefold more represented in AD patients than in controls (2.0% vs 0.8%;
      p=0.031), and it might account for the increased frequency of H5 in AD patients
      (4.2% vs 2.3%). The complete re-sequencing of the 56 mtDNAs belonging to H5
      revealed that AD patients showed a trend towards a higher number (p=0.052) of
      sporadic mutations in tRNA and rRNA genes when compared with controls.
      CONCLUSIONS: Our results indicate that high resolution analysis of inherited
      mtDNA sequence variation can help in identifying both ancient polymorphisms
      defining sub-haplogroups and the accumulation of sporadic mutations associated
      with complex traits such as AD.

PMID- 20700463
TI  - Unrelated helpers in a primitively eusocial wasp: is helping tailored towards
      direct fitness?
AB  - The paper wasp Polistes dominulus is unique among the social insects in that
      nearly one-third of co-foundresses are completely unrelated to the dominant
      individual whose offspring they help to rear and yet reproductive skew is high.
      These unrelated subordinates stand to gain direct fitness through nest
      inheritance, raising the question of whether their behaviour is adaptively
      tailored towards maximizing inheritance prospects. Unusually, in this species, a
      wealth of theory and empirical data allows us to predict how unrelated
      subordinates should behave. Based on these predictions, here we compare helping
      in subordinates that are unrelated or related to the dominant wasp across an
      extensive range of field-based behavioural contexts. We find no differences in
      foraging effort, defense behaviour, aggression or inheritance rank between
      unrelated helpers and their related counterparts. Our study provides no evidence,
      across a number of behavioural scenarios, that the behaviour of unrelated
      subordinates is adaptively modified to promote direct fitness interests.

PMID- 20700464
TI  - Localized fetomaternal hyperglycemia: spatial and kinetic definition by positron
      emission tomography.
AB  - BACKGROUND: Complex but common maternal diseases such as diabetes and obesity
      contribute to adverse fetal outcomes. Understanding of the mechanisms involved is
      hampered by difficulty in isolating individual elements of complex maternal
      states in vivo. We approached this problem in the context of maternal diabetes
      and sought an approach to expose the developing fetus in vivo to isolated
      hyperglycemia in the pregnant rat. METHODOLOGY AND PRINCIPAL FINDINGS: We
      hypothesized that glucose infused into the arterial supply of one uterine horn
      would more highly expose fetuses in the ipsilateral versus contralateral uterine
      horn. To test this, the glucose tracer [18F]fluorodeoxyglucose (FDG) was infused
      via the left uterine artery. Regional glucose uptake into maternal tissues and
      fetuses was quantified using positron emission tomography (PET). Upon infusion,
      FDG accumulation began in the left-sided placentae, subsequently spreading to the
      fetuses. Over two hours after completion of the infusion, FDG accumulation was
      significantly greater in left compared to right uterine horn fetuses, favoring
      the left by 1.9+/-0.1 and 2.8+/-0.3 fold under fasted and hyperinsulinemic
      conditions (p<10(-11) n=32-35 and p<10(-12) n=27-45) respectively. By contrast,
      centrally administered [3H]-2-deoxyglucose accumulated equally between the
      fetuses of the two uterine horns. Induction of significant hyperglycemia (10(3)
      mg/dL) localized to the left uterine artery was sustained for at least 48 hours
      while maternal euglycemia was maintained. CONCLUSIONS AND SIGNIFICANCE: This
      approach exposes selected fetuses to localized hyperglycemia in vivo, minimizing
      exposure of the mother and thus secondary effects. Additionally, a set of less
      exposed internal control fetuses are maintained for comparison, allowing direct
      study of the in vivo fetal effects of isolated hyperglycemia. Broadly, this
      approach can be extended to study a variety of maternal-sided perturbations
      suspected to directly affect fetal health.

PMID- 20700465
TI  - Involvement of Caveolin-1 in repair of DNA damage through both homologous
      recombination and non-homologous end joining.
AB  - BACKGROUND: Caveolin-1 (Cav-1), the major component of caveolae, is a 21-24 kDa
      integral membrane protein that interacts with a number of signaling molecules. By
      acting as a scaffolding protein, Cav-1 plays crucial roles in the regulation of
      various physiologic and patho-physiologic processes including oncogenic
      transformation and tumorigenesis, and tumor invasion and metastasis.
      METHODOLOGY/PRINCIPAL FINDINGS: In the present study we sought to explore the
      role of Cav-1 in response to DNA damage and the mechanism involved. We found that
      the level of Cav-1 was up-regulated rapidly in cells treated with ionizing
      radiation. The up-regulation of Cav-1 following DNA damage occurred only in cells
      expressing endogenous Cav-1, and was associated with the activation of DNA damage
      response pathways. Furthermore, we demonstrated that the expression of Cav-1
      protected cells against DNA damage through modulating the activities of both the
      homologous recombination (HR) and non-homologous end joining (NHEJ) repair
      systems, as evidenced by the inhibitory effects of the Cav-1-targeted siRNA on
      cell survival, HR frequency, phosphorylation of DNA-dependent protein kinase (DNA
      PK), and nuclear translocation of epidermal growth factor receptor (EGFR)
      following DNA damage, and by the stimulatory effect of the forced expression of
      Cav-1 on NHEJ frequency. CONCLUSION/SIGNIFICANCE: Our results indicate that Cav-1
      may play a critical role in sensing genotoxic stress and in orchestrating the
      response of cells to DNA damage through regulating the important molecules
      involved in maintaining genomic integrity.

PMID- 20700466
TI  - Phylogenetic constraints do not explain the rarity of nitrogen-fixing trees in
      late-successional temperate forests.
AB  - BACKGROUND: Symbiotic nitrogen (N)-fixing trees are rare in late-successional
      temperate forests, even though these forests are often N limited. Two hypotheses
      could explain this paradox. The 'phylogenetic constraints hypothesis' states that
      no late-successional tree taxa in temperate forests belong to clades that are
      predisposed to N fixation. Conversely, the 'selective constraints hypothesis'
      states that such taxa are present, but N-fixing symbioses would lower their
      fitness. Here we test the phylogenetic constraints hypothesis.
      METHODOLOGY/PRINCIPAL FINDINGS: Using U.S. forest inventory data, we derived
      successional indices related to shade tolerance and stand age for N-fixing trees,
      non-fixing trees in the 'potentially N-fixing clade' (smallest angiosperm clade
      that includes all N fixers), and non-fixing trees outside this clade. We then
      used phylogenetically independent contrasts (PICs) to test for associations
      between these successional indices and N fixation. Four results stand out from
      our analysis of U.S. trees. First, N fixers are less shade-tolerant than non
      fixers both inside and outside of the potentially N-fixing clade. Second, N
      fixers tend to occur in younger stands in a given geographical region than non
      fixers both inside and outside of the potentially N-fixing clade. Third, the
      potentially N-fixing clade contains numerous late-successional non-fixers.
      Fourth, although the N fixation trait is evolutionarily conserved, the
      successional traits are relatively labile. CONCLUSIONS/SIGNIFICANCE: These
      results suggest that selective constraints, not phylogenetic constraints, explain
      the rarity of late-successional N-fixing trees in temperate forests. Because N
      fixing trees could overcome N limitation to net primary production if they were
      abundant, this study helps to understand the maintenance of N limitation in
      temperate forests, and therefore the capacity of this biome to sequester carbon.

PMID- 20700467
TI  - A Bayesian approach to the evolution of metabolic networks on a phylogeny.
AB  - The availability of genomes of many closely related bacteria with diverse
      metabolic capabilities offers the possibility of tracing metabolic evolution on a
      phylogeny relating the genomes to understand the evolutionary processes and
      constraints that affect the evolution of metabolic networks. Using simple
      (independent loss/gain of reactions) or complex (incorporating dependencies among
      reactions) stochastic models of metabolic evolution, it is possible to study how
      metabolic networks evolve over time. Here, we describe a model that takes the
      reaction neighborhood into account when modeling metabolic evolution. The model
      also allows estimation of the strength of the neighborhood effect during the
      course of evolution. We present Gibbs samplers for sampling networks at the
      internal node of a phylogeny and for estimating the parameters of evolution over
      a phylogeny without exploring the whole search space by iteratively sampling from
      the conditional distributions of the internal networks and parameters. The
      samplers are used to estimate the parameters of evolution of metabolic networks
      of bacteria in the genus Pseudomonas and to infer the metabolic networks of the
      ancestral pseudomonads. The results suggest that pathway maps that are conserved
      across the Pseudomonas phylogeny have a stronger neighborhood structure than
      those which have a variable distribution of reactions across the phylogeny, and
      that some Pseudomonas lineages are going through genome reduction resulting in
      the loss of a number of reactions from their metabolic networks.

PMID- 20700468
TI  - Morphology, Ontogenesis and Molecular Phylogeny of Neokeronopsis (Afrokeronopsis)
      aurea nov. subgen., nov. spec. (Ciliophora: Hypotricha), a New African Flagship
      Ciliate Confirms the CEUU Hypothesis.
AB  - Neokeronopsis (Afrokeronopsis) aurea nov. subgen., nov. spec. was discovered in
      soil from the floodplain of a small river in the Krueger National Park, Republic
      of South Africa. Its morphology, ontogenesis, and 18S rDNA were studied with
      standard methods. Furthermore, we supplemented the data on N. (N.) spectabilis by
      reinvestigating the preparations deposited in the British Museum of Natural
      History. Neokeronopsis (Afrokeronopsis) aurea is a very conspicuous ciliate
      because it has an average size of 330 * 120 MUm and is golden yellow due to the
      orange-coloured cytoplasm and citrine cortical granules. Further main
      characteristics include the semirigid body; the urostylid cirral pattern with a
      distinct corona of frontal and pseudobuccal cirri both originating from the
      midventral rows; multiple anterior fragmentation of dorsal kineties 1-3; multiple
      posterior fragmentation of kinety 3, commencing with an unique whirl of
      kinetofragments; three caudal cirri; an oxytrichid/cyrtohymenid oral apparatus
      with polystichad paroral membrane and buccal depression; a single oral primordium
      developing along the transverse cirral row; and an oxytrichid 18S rDNA. These
      peculiarities are used to establish the new oxytrichid family Neokeronopsidae,
      the new subgenus Afrokeronopsis, and the new species N. (A.) aurea. Further,
      these features confirm the CEUU hypothesis, i.e., convergent evolution of a
      midventral cirral pattern in urostylid and oxytrichid hypotrichs; additionally,
      N. (A.) aurea is the first (semi)rigid hypotrich with cortical granules and the
      second one with midventral rows, breaking the granule and flexibility dogmas.
      These and other observations show that the phylogeny of the hypotrichs is full of
      convergences. Thus, only a combined effort of classical and molecular
      phylogeneticists will provide the data needed for a natural classification. Based
      on the CEUU hypothesis, the molecular data, and literature evidence, we suggest
      that midventral oxytrichids should be ranked as distinct families; accordingly,
      we establish a further new family, the Uroleptidae, which forms a distinct clade
      within the oxytrichid molecular trees. Neokeronopsis is possibly related to
      Pattersoniella because it has the same special mode of forming the buccal cirri
      and possesses a buccal depression found also in Steinia, a close relative of
      Pattersoniella. The large size and conspicuous colour make N. (A.) aurea a
      biogeographic flagship possibly confined to Africa or Gondwana, while
      Neokeronopsis (N.) spectabilis (Kahl, 1932) is an Eurasian flagship.

PMID- 20700469
TI  - Overexpression of POLQ confers a poor prognosis in early breast cancer patients.
AB  - Depletion of POLQ (DNA polymerase theta) has recently been shown to render tumour
      cells more sensitive to radiotherapy whilst having little or no effect on normal
      tissues. This finding led us to investigate whether tumours that overexpress POLQ
      are associated with an adverse outcome. We therefore correlated the clinical
      outcomes of two retrospective series of patients with early breast cancer with
      the expression levels of POLQ, as determined by microarray gene expression
      analysis. We found that a significant number of tumours overexpressed POLQ and
      that overexpression was correlated with ER negative disease (p=0.047) and high
      tumour grade (p=0.004), both of which are associated with poor clinical outcomes.
      POLQ overexpression was associated with poor relapse free survival rates on both
      univariate (HR 5.80; 95% CI, 2.220 to 15.159; p<0.001) and multivariate analysis
      (HR 8.086; 95% CI 2.340 to 27.948 p=0.001). Analysis of other published clinical
      series confirmed that POLQ overexpression is associated with adverse clinical
      outcomes. The poor prognosis associated with POLQ is independent of other
      clinical or pathological features. The mechanism that causes this adverse outcome
      remains to be elucidated but may in part arise from resistance to adjuvant
      treatment. These findings, combined with the limited normal tissue expression of
      POLQ, make it a very appealing target for possible clinical exploitation.

PMID- 20700470
TI  - The Neurobiological Basis of Cognition: Identification by Multi-Input,
      Multioutput Nonlinear Dynamic Modeling: A method is proposed for measuring and
      modeling human long-term memory formation by mathematical analysis and computer
      simulation of nerve-cell dynamics.
AB  - The successful development of neural prostheses requires an understanding of the
      neurobiological bases of cognitive processes, i.e., how the collective activity
      of populations of neurons results in a higher level process not predictable based
      on knowledge of the individual neurons and/or synapses alone. We have been
      studying and applying novel methods for representing nonlinear transformations of
      multiple spike train inputs (multiple time series of pulse train inputs) produced
      by synaptic and field interactions among multiple subclasses of neurons arrayed
      in multiple layers of incompletely connected units. We have been applying our
      methods to study of the hippocampus, a cortical brain structure that has been
      demonstrated, in humans and in animals, to perform the cognitive function of
      encoding new long-term (declarative) memories. Without their hippocampi, animals
      and humans retain a short-term memory (memory lasting approximately 1 min), and
      long-term memory for information learned prior to loss of hippocampal function.
      Results of more than 20 years of studies have demonstrated that both individual
      hippocampal neurons, and populations of hippocampal cells, e.g., the neurons
      comprising one of the three principal subsystems of the hippocampus, induce
      strong, higher order, nonlinear transformations of hippocampal inputs into
      hippocampal outputs. For one synaptic input or for a population of synchronously
      active synaptic inputs, such a transformation is represented by a sequence of
      action potential inputs being changed into a different sequence of action
      potential outputs. In other words, an incoming temporal pattern is transformed
      into a different, outgoing temporal pattern. For multiple, asynchronous synaptic
      inputs, such a transformation is represented by a spatiotemporal pattern of
      action potential inputs being changed into a different spatiotemporal pattern of
      action potential outputs. Our primary thesis is that the encoding of short-term
      memories into new, long-term memories represents the collective set of
      nonlinearities induced by the three or four principal subsystems of the
      hippocampus, i.e., entorhinal cortex-to-dentate gyrus, dentate gyrus-to-CA3
      pyramidal cell region, CA3-to-CA1 pyramidal cell region, and CA1-to-subicular
      cortex. This hypothesis will be supported by studies using in vivo hippocampal
      multineuron recordings from animals performing memory tasks that require
      hippocampal function. The implications for this hypothesis will be discussed in
      the context of "cognitive prostheses"-neural prostheses for cortical brain
      regions believed to support cognitive functions, and that often are subject to
      damage due to stroke, epilepsy, dementia, and closed head trauma.

PMID- 20700471
TI  - Alcohol use and gender effects on HIV risk behaviors in cocaine-using methadone
      patients.
AB  - Injection drug users engage in behaviors that increase the spread of human
      immunodeficiency virus (HIV) and other infectious diseases. Although methadone
      maintenance (MM) is highly effective in decreasing heroin use and the spread of
      HIV, polydrug use, especially the combined use of cocaine and alcohol, is common
      in MM patients. Alcohol use is independently associated with HIV risk behaviors,
      and the effects of alcohol use on risk behaviors may vary by gender. This study
      evaluated the effects of recent heavy alcohol use and gender with respect to HIV
      risk behaviors in 118 cocaine-abusing methadone patients. Both lifetime and past
      month injection and sexual risk behaviors were examined. Recent heavy drinkers (n
      = 46) were more likely to be male than nonheavy drinkers (n = 72). Recent heavy
      drinkers reported more risky sexual behaviors over their lifetimes than nonheavy
      drinkers. Gender effects were also present for lifetime risk behaviors, with
      females demonstrating more sexual and injection risk behaviors than men. In terms
      of recent injection risk behaviors, there was a significant alcohol use by gender
      effect. Heavy drinking females reported significantly more drug-sharing behaviors
      and less frequent needle cleaning than nonheavy drinking females. Recent sexual
      behaviors did not differ based on alcohol use status or gender. These findings
      may inform HIV prevention strategies in cocaine-abusing MM patients, and they
      suggest that cocaine-abusing women who drink heavily are a particularly high risk
      group who should be counseled about risky injection drug use practices.

PMID- 20700472
TI  - Molecular Biomechanics: The Molecular Basis of How Forces Regulate Cellular
      Function.
AB  - Recent advances have led to the emergence of molecular biomechanics as an
      essential element of modern biology. These efforts focus on theoretical and
      experimental studies of the mechanics of proteins and nucleic acids, and the
      understanding of the molecular mechanisms of stress transmission, mechanosensing
      and mechanotransduction in living cells. In particular, single-molecule
      biomechanics studies of proteins and DNA, and mechanochemical coupling in
      biomolecular motors have demonstrated the critical importance of molecular
      mechanics as a new frontier in bioengineering and life sciences. To stimulate a
      more systematic study of the basic issues in molecular biomechanics, and attract
      a broader range of researchers to enter this emerging field, here we discuss its
      significance and relevance, describe the important issues to be addressed and the
      most critical questions to be answered, summarize both experimental and
      theoretical/computational challenges, and identify some short-term and long-term
      goals for the field. The needs to train young researchers in molecular
      biomechanics with a broader knowledge base, and to bridge and integrate
      molecular, subcellular and cellular level studies of biomechanics are
      articulated.

PMID- 20700473
TI  - How cofilin severs an actin filament.
AB  - The actin regulatory protein, cofilin, promotes actin assembly dynamics by
      severing filaments and increasing the number of ends from which subunits add and
      dissociate. Recent studies provide biophysical descriptions of cooperative
      filament interactions in energetic, mechanical and structural terms. A one
      dimensional Ising model with nearest-neighbor interactions permits thermodynamic
      analysis of cooperative binding and indicates that one or a few cofilin molecules
      can sever a filament. Binding and cooperative interactions are entropically
      driven. A significant fraction of the binding free energy results from the linked
      dissociation of filament-associated ions (polyelectrolyte effect), which modulate
      filament structure, stability and mechanics. The remaining binding free energy
      and essentially all of the cooperative free energy arise from the enhanced
      conformational dynamics of the cofilactin complex. Filament mechanics are
      modulated by cofilin such that cofilin-saturated filaments are approximately 10-
      to 20-fold more compliant in bending and twisting than bare filaments. Cofilin
      activity is well described by models in which discontinuities in topology,
      mechanics and conformational dynamics generate stress concentration and promote
      fracture at junctions of bare and decorated segments, analogous to the grain
      boundary fracture of crystalline materials and the thermally driven formation of
      shear transformation zones in colloidal glass.

PMID- 20700474
TI  - Imaging surface immobilization chemistry: correlation with cell patterning on non
      adhesive hydrogel thin films.
AB  - High-fidelity surface functional group (e.g., N-hydroxysuccinimide (NHS) reactive
      ester) patterning is readily and reliably achieved on commercial poly(ethylene
      glycol) (PEG)-based polymer films already known to exhibit high performance non
      fouling properties in full serum and in cell culture conditions. NHS coupling
      chemistry co-patterned with methoxy-capped PEG using photolithographic methods is
      directly spatially imaged using imaging time-of-flight secondary ion mass
      spectrometry (ToF-SIMS) and principal components statistical analysis. Patterned
      NHS surface reactive zones are clearly resolved at high sensitivity despite the
      complexity of the polymer matrix chemistry. ToF-SIMS imaging also reveals the
      presence of photo-resist residue remaining from typical photolithography
      processing methods. High cross-correlation between various ion-derived ToF-SIMS
      images is observed, providing sensitive chemical corroboration of pattern
      chemistry and biological reactivity in complex milieu. Surface-specific protein
      coupling is observed first by site-selective reaction of streptavidin with NHS
      patterns, followed by identical patterns of biotinylated Alexa-labeled albumin
      coupling. This suggests that streptavidin immobilized on the patterns remains
      bioactive. Fluorescently labeled full serum is shown to react selectively with
      NHS-reactive regions, with minimal signal from methoxy-capped regions.
      Insufficient serum is adsorbed under any conditions to these surfaces to support
      cell attachment in serum-containing media. This reflects the high intrinsic non
      adsorptive nature of this chemistry. Fibroblasts attach and proliferate in serum
      culture only when a cell adhesion peptide (RGD) is first grafted to NHS regions
      on the PEG-based surfaces. Longer-term serum-based cell culture retains high cell
      pattern fidelity that correlates with chemical imaging of both the NHS and RGD
      patterns and also lack of cell adhesion to methoxy-capped regions. Cell staining
      shows orientation of adherent cells within the narrow patterned areas. Cell
      patterns are consistently retained beyond 15 days in serum media.

PMID- 20700475
TI  - Gender and racial differences in risk factors for sexually transmitted diseases
      among justice-involved youth.
AB  - Gender and racial differences in infection rates for chlamydia and gonorrhea have
      been reported within community-based populations, but little is known of such
      differences within juvenile offending populations. Moreover, while research has
      demonstrated that certain individual-level and community-level factors affect
      risky behaviors associated with sexually transmitted disease (STD), less is known
      about how multi-level factors affect STD infection, particularly among delinquent
      populations. The present study investigated gender and racial differences in STD
      infection among a sample of 924 juvenile offenders. Generalized linear model
      regression analyses were conducted to examine the influence of individual-level
      factors such as age, offense history, and substance use and community-level
      factors such as concentrated disadvantage, ethnic heterogeneity, and family
      disruption on STD status. Results revealed significant racial and STD status
      differences across gender, as well as interaction effects for race and STD status
      for males only. Gender differences in individual-level and community-level
      predictors were also found. Implications of these findings for future research
      and public health policy are discussed.

PMID- 20700476
TI  - Interactive Design Strategy for a Multi-Functional PAMAM Dendrimer-Based Nano
      Therapeutic Using Computational Models and Experimental Analysis.
AB  - Molecular dynamics simulations of nano-therapeutics as a final product and of all
      intermediates in the process of generating a multi-functional nano-therapeutic
      based on a poly(amidoamine) (PAMAM) dendrimer were performed along with chemical
      analyses of each of them. The actual structures of the dendrimers were predicted,
      based on potentiometric titration, gel permeation chromatography, and NMR. The
      chemical analyses determined the numbers of functional molecules, based on the
      actual structure of the dendrimer. Molecular dynamics simulations calculated the
      configurations of the intermediates and the radial distributions of functional
      molecules, based on their numbers. This interactive process between the
      simulation results and the chemical analyses provided a further strategy to
      design the next reaction steps and to gain insight into the products at each
      chemical reaction step.

PMID- 20700477
TI  - Reconsidering the Northwest European Family System: Living Arrangements of the
      Aged in Comparative Historical Perspective.

PMID- 20700478
TI  - Antecedent caloric intake and glucose excursion following a subsequent meal in
      Type 1 diabetes.
AB  - BACKGROUND: In the present study, we tested the hypothesis that calories consumed
      at a prior meal (lunch) may impair glycemic control after a subsequent meal
      (supper) even if the pre-supper glucose did not differ regardless of the size of
      the lunch meal. METHODS: Nine subjects with Type 1 diabetes using continuous
      subcutaneous (s.c.) insulin infusion (CSII) therapy were studied on two separate
      days. Lunch (1200 h) was randomly assigned as 25% or 50% of the usual daily
      intake on alternate study days. The CSII was stopped at 1000 h on the day of the
      study and glucose was controlled until supper by adjusting the rate of
      intravenous (i.v.) insulin based on glucose measurements every 15 min. The CSII
      was restarted 1 h before supper and i.v. insulin discontinued 15 min before the
      first bite of supper. An identical supper meal and pre-supper s.c. bolus of short
      acting insulin were administered on both visits. RESULTS: Pre-supper glycemia was
      nearly identical on each of the two study days. However, the post-supper glucose
      area under the curve was 27.5% greater on the day of the antecedent large lunch
      compared with the small lunch (P = 0.0039). CONCLUSIONS: For optimal postprandial
      glucose control, people with Type 1 diabetes may need to consider not only
      anticipated meal calories, but also prior food intake, a practice not commonly
      recommended based on currently used insulin dosing algorithms.

PMID- 20700479
TI  - Managing Chaos: Lessons Learned Developing Software in the Life Sciences.

PMID- 20700480
TI  - Label-free biosensing using a photonic crystal structure in a total-internal
      reflection geometry.
AB  - A novel optical biosensor using a one-dimensional photonic crystal structure in a
      total-internal-reflection geometry (PC-TIR) is presented and investigated for
      label-free biosensing applications. This simple configuration forms a micro Fabry
      Perot resonator in the top layer which provides a narrow optical resonance to
      enable label-free, highly sensitive measurements for the presence of analytes on
      the sensing surface or the refractive index change of the surrounding medium in
      the enhanced evanescent field; and at the same time it employs an open sensing
      surface for real-time biomolecular binding detection. The high sensitivity of the
      sensor was experimentally demonstrated by bulk solvent refractive index changes,
      ultrathin molecular films adsorbed on the sensing surface, and real-time analytes
      binding, measuring both the spectral shift of the photonic crystal resonance and
      the change of the intensity ratio in a differential reflectance measurement.
      Detection limits of 7x10(-8) RIU for bulk solvent refractive index, 6x10(-5) nm
      for molecular layer thickness and 24 fg/mm(2) for mass density were obtained,
      which represent a significant improvement relative to state-of-the-art surface
      plasmon-resonance (SPR)-based systems. The PC-TIR sensor is thus seen to be a
      promising technology platform for high sensitivity and accurate biomolecular
      detection.

PMID- 20700481
TI  - Investigation of Respiratory Gating in Quantitative Myocardial SPECT.
AB  - The purpose of this study is to investigate optimal respiratory gating schemes
      using different numbers of gates and placements within the respiratory cycle for
      reduction of respiratory motion (RM) artifacts in myocardial SPECT. The 4D NCAT
      phantom with its realistic respiratory model was used to generate 96 3D phantoms
      equally spaced over a complete respiratory cycle modeling the activity
      distribution from a typical Tc-99m Sestamibi study with the maximum movement of
      the diaphragm set at 2 cm. The 96 time frames were grouped to simulate various
      gating schemes (1, 3, 6, and 8 equally spaced gates) and different placements of
      the gates within a respiratory cycle. Projection data, including effects of
      attenuation, collimator-detector response and scatter, from each respiratory gate
      and each gating scheme were generated and reconstructed using the OS-EM algorithm
      with correction for attenuation. Attenuation correction was done with average
      attenuation maps for each gate and over the entire respiratory cycle. Bull's-eye
      polar plots generated from the reconstructed images for each gate were analyzed
      and compared to assess the effect of RM. RM artifacts were found to be reduced
      the most when going from the ungated to the gated case. No significant difference
      was found in attenuation compensated images between the use of gated and average
      attenuation maps. Our results indicate that the extent of RM artifacts is
      dependent on the placement of the gates in a gating scheme. Artifacts are less
      prominent in gates near end-expiration and more prominent near end-inspiration.
      This dependence on gate placement decreases when going to higher numbers of gates
      (6 and higher). However, it is possible to devise a non-uniform time interval
      gating scheme with 3 gates that will produce results similar to those using a
      higher number of gates. We conclude that respiratory gating is an effective way
      to reduce RM artifacts. Effective implementation of respiratory gating to further
      improve quantitative myocardial SPECT requires optimization of the gating scheme
      based on the amount of respiratory motion of the heart during each gate and the
      placement of the gates within the respiratory cycle.

PMID- 20700482
TI  - Polymer Microring Resonators for High-Frequency Ultrasound Detection and Imaging.
AB  - Polymer microring resonators fabricated by nanoimprinting are presented as a
      means of ultrasound detection. Acoustic waves impinging on a ring-shaped optical
      resonator cause strain in the ring dimensions, modulating optical output. Basic
      acoustic and optical characteristics of the microring sensor are presented.
      Measurements at several frequencies show a high sensitivity and low noise
      equivalent pressure. The angular response is determined by sensing the
      optoacoustic excitation of a 49 MUm polyester microsphere and shows wide-angle
      sensitivity. A 1-D array consisting of 4 microrings is demonstrated using
      wavelength multiplexing for addressing each element. The high sensitivity,
      bandwidth, and angular response make it a potentially useful sensor platform for
      many applications including high-frequency ultrasonic and photoacoustic imaging.

PMID- 20700483
TI  - Single-unit activity in the medial prefrontal cortex during immediate and delayed
      extinction of fear in rats.
AB  - Delivering extinction trials minutes after fear conditioning yields only a short
      term fear suppression that fully recovers the following day. Because extinction
      has been reported to increase CS-evoked spike firing and spontaneous bursting in
      the infralimbic (IL) division of the medial prefrontal cortex (mPFC), we explored
      the possibility that this immediate extinction deficit is related to altered mPFC
      function. Single-units were simultaneously recorded in rats from neurons in IL
      and the prelimbic (PrL) division of the mPFC during an extinction session
      conducted 10 minutes (immediate) or 24 hours (delayed) after auditory fear
      conditioning. In contrast to previous reports, IL neurons exhibited CS-evoked
      responses early in extinction training in both immediate and delayed conditions
      and these responses decreased in magnitude over the course of extinction
      training. During the retention test, CS-evoked firing in IL was significantly
      greater in animals that failed to acquire extinction. Spontaneous bursting during
      the extinction and test sessions was also different in the immediate and delayed
      groups. There were no group differences in PrL activity during extinction or
      retention testing. Alterations in both spontaneous and CS-evoked neuronal
      activity in the IL may contribute to the immediate extinction deficit.

PMID- 20700484
TI  - NPRL2 sensitizes human non-small cell lung cancer (NSCLC) cells to cisplatin
      treatment by regulating key components in the DNA repair pathway.
AB  - NPRL2, one of the tumor suppressor genes residing in a 120-kb homozygous deletion
      region of human chromosome band 3p21.3, has a high degree of amino acid sequence
      homology with the nitrogen permease regulator 2 (NPR2) yeast gene, and mutations
      of NPRL2 in yeast cells are associated with resistance to cisplatin-mediated cell
      killing. Previously, we showed that restoration of NPRL2 in NPRL2-negative and
      cisplatin-resistant cells resensitize lung cancer cells to cisplatin treatment in
      vitro and in vivo. In this study, we show that sensitization of non-small cell
      lung cancer (NSCLC) cells to cisplatin by NPRL2 is accomplished through the
      regulation of key components in the DNA-damage checkpoint pathway. NPRL2 can
      phosphorylate ataxia telangiectasia mutated (ATM) kinase activated by cisplatin
      and promote downstream gamma-H2AX formation in vitro and in vivo, which occurs
      during apoptosis concurrently with the initial appearance of high-molecular
      weight DNA fragments. Moreover, this combination treatment results in higher Chk1
      and Chk2 kinase activity than does treatment with cisplatin alone and can
      activate Chk2 in pleural metastases tumor xenograft in mice. Activated Chk1 and
      Chk2 increase the expression of cell cycle checkpoint proteins, including Cdc25A
      and Cdc25C, leading to higher levels of G2/M arrest in tumor cells treated with
      NPRL2 and cisplatin than in tumor cells treated with cisplatin only. Our results
      therefore suggest that ectopic expression of NPRL2 activates the DNA damage
      checkpoint pathway in cisplatin-resistant and NPRL2-negative cells; hence, the
      combination of NPRL2 and cisplatin can resensitize cisplatin nonresponders to
      cisplatin treatment through the activation of the DNA damage checkpoint pathway,
      leading to cell arrest in the G2/M phase and induction of apoptosis. The direct
      implication of this study is that combination treatment with NPRL2 and cisplatin
      may overcome cisplatin resistance and enhance therapeutic efficacy.

PMID- 20700485
TI  - Evidence for the existence of secretory granule (dense-core vesicle)-based
      inositol 1,4,5-trisphosphate-dependent Ca2+ signaling system in astrocytes.
AB  - BACKGROUND: The gliotransmitters released from astrocytes are deemed to play key
      roles in the glial cell-neuron communication for normal function of the brain.
      The gliotransmitters, such as glutamate, ATP, D-serine, neuropeptide Y, are
      stored in vesicles of astrocytes and secreted following the inositol 1,4,5
      trisphosphate (IP3)-induced intracellular Ca2+ releases. Yet studies on the
      identity of the IP3-dependent intracellular Ca2+ stores remain virtually
      unexplored. PRINCIPAL FINDINGS: We have therefore studied the potential existence
      of the IP3-sensitive intracellular Ca2+ stores in the cytoplasm of astrocytes
      using human brain tissue samples in contrast to cultured astrocytes that had
      primarily been used in the past. It was thus found that secretory granule marker
      proteins chromogranins and secretogranin II localize in the large dense core
      vesicles of astrocytes, thereby confirming the large dense core vesicles as bona
      fide secretory granules. Moreover, consistent with the major IP3-dependent
      intracellular Ca2+ store role of secretory granules in secretory cells, secretory
      granules of astrocytes also contained all three (types 1, 2, and 3) IP3R
      isoforms. SIGNIFICANCE: Given that the secretory granule marker proteins
      chromogranins and secretogranin II are high-capacity, low-affinity Ca2+ storage
      proteins and chromogranins interact with the IP3Rs to activate the IP3R/Ca2+
      channels, i.e., increase both the mean open time and the open probability of the
      channels, these results imply that secretory granules of astrocytes function as
      the IP3-sensitive intracellular Ca2+ store.

PMID- 20700486
TI  - A first generation BAC-based physical map of the Asian seabass (Lates
      calcarifer).
AB  - BACKGROUND: The Asian seabass (Lates calcarifer) is an important marine foodfish
      species in Southeast Asia and Australia. Genetic improvement of this species has
      been achieved to some extent through selective breeding programs since 1990s.
      Several genomic tools such as DNA markers, a linkage map, cDNA and BAC libraries
      have been developed to assist selective breeding. A physical map is still
      lacking, although it is essential for positional cloning of genes located in
      quantitative trait loci (QTL) and assembly of whole genome sequences.
      METHODOLOGY/PRINCIPAL FINDINGS: A genome-wide physical map of the Asian seabass
      was constructed by restriction fingerprinting of 38,208 BAC clones with SNaPshot
      HICF FPC technique. A total of 30,454 were assembled into 2,865 contigs. The
      physical length of the assembled contigs summed up to 665 Mb. Analyses of some
      contigs using different methods demonstrated the reliability of the assembly.
      CONCLUSIONS/SIGNIFICANCE: The present physical map is the first physical map for
      Asian seabass. This physical map will facilitate the fine mapping of QTL for
      economically important traits and the positional cloning of genes located in QTL.
      It will also be useful for the whole genome sequencing and assembly. Detailed
      information about BAC-contigs and BAC clones are available upon request.

PMID- 20700487
TI  - Use of activity-based probes to develop high throughput screening assays that can
      be performed in complex cell extracts.
AB  - BACKGROUND: High throughput screening (HTS) is one of the primary tools used to
      identify novel enzyme inhibitors. However, its applicability is generally
      restricted to targets that can either be expressed recombinantly or purified in
      large quantities. METHODOLOGY AND PRINCIPAL FINDINGS: Here, we described a method
      to use activity-based probes (ABPs) to identify substrates that are sufficiently
      selective to allow HTS in complex biological samples. Because ABPs label their
      target enzymes through the formation of a permanent covalent bond, we can
      correlate labeling of target enzymes in a complex mixture with inhibition of
      turnover of a substrate in that same mixture. Thus, substrate specificity can be
      determined and substrates with sufficiently high selectivity for HTS can be
      identified. In this study, we demonstrate this method by using an ABP for
      dipeptidyl aminopeptidases to identify (Pro-Arg)2-Rhodamine as a specific
      substrate for DPAP1 in Plasmodium falciparum lysates and Cathepsin C in rat liver
      extracts. We then used this substrate to develop highly sensitive HTS assays
      (Z'>0.8) that are suitable for use in screening large collections of small
      molecules (i.e >300,000) for inhibitors of these proteases. Finally, we
      demonstrate that it is possible to use broad-spectrum ABPs to identify target
      specific substrates. CONCLUSIONS: We believe that this approach will have value
      for many enzymatic systems where access to large amounts of active enzyme is
      problematic.

PMID- 20700488
TI  - EPO receptor gain-of-function causes hereditary polycythemia, alters CD34 cell
      differentiation and increases circulating endothelial precursors.
AB  - BACKGROUND: Gain-of-function of erythropoietin receptor (EPOR) mutations
      represent the major cause of primary hereditary polycythemia. EPOR is also found
      in non-erythroid tissues, although its physiological role is still undefined.
      METHODOLOGY/PRINCIPAL FINDINGS: We describe a family with polycythemia due to a
      heterozygous mutation of the EPOR gene that causes a G-->T change at nucleotide
      1251 of exon 8. The novel EPOR G1251T mutation results in the replacement of a
      glutamate residue by a stop codon at amino acid 393. Differently from
      polycythemia vera, EPOR G1251T CD34(+) cells proliferate and differentiate
      towards the erythroid phenotype in the presence of minimal amounts of EPO.
      Moreover, the affected individuals show a 20-fold increase of circulating
      endothelial precursors. The analysis of erythroid precursor membranes
      demonstrates a heretofore undescribed accumulation of the truncated EPOR,
      probably due to the absence of residues involved in the EPO-dependent receptor
      internalization and degradation. Mutated receptor expression in EPOR-negative
      cells results in EPOR and Stat5 phosphorylation. Moreover, patient erythroid
      precursors present an increased activation of EPOR and its effectors, including
      Stat5 and Erk1/2 pathway. CONCLUSIONS/SIGNIFICANCE: Our data provide an
      unanticipated mechanism for autosomal dominant inherited polycythemia due to a
      heterozygous EPOR mutation and suggest a regulatory role of EPO/EPOR pathway in
      human circulating endothelial precursors homeostasis.

PMID- 20700489
TI  - The chemokine CXCL13 is a prognostic marker in clinically isolated syndrome
      (CIS).
AB  - BACKGROUND: There is increasing recognition of the importance of B lymphocytes in
      the immunopathogenesis of multiple sclerosis (MS), encouraging the evaluation of
      B cell-associated biomarkers in the cerebrospinal fluid (CSF). We aimed to
      evaluate the relevance of the B cell chemoattractant CXCL13 as a prognostic
      marker in patients with clinically isolated syndrome (CIS) regarding conversion
      to MS, and to compare it to Barkhof criteria in magnetic resonance imaging (MRI),
      oligoclonal bands (OCB) and the polyspecific intrathecal B cell response against
      measles, rubella and varicella zoster virus (MRZR). METHODOLOGY/PRINCIPAL
      FINDINGS: CXCL13 was determined in a prospective study over 2 years including 46
      patients that remained CIS over follow-up (CIS-CIS), 45 patients that developed
      MS (CIS-RRMS), and 30 controls using ELISA. CSF CXCL13 was significantly elevated
      in CIS-RRMS as compared to CIS-CIS and controls (p<0.001). It was significantly
      elevated in CIS with OCB (p<0.001), positive MRZR (p=0.04), and gadolinium
      enhancement in MRI (p=0.02) and showed a significant correlation with CSF
      leukocyte count (p<0.001) and QIgG (p<0.001). CXCL13 showed the best positive
      predictive value (PPV) of all parameters investigated (70%, 95%-CI: 53-84%),
      which could be further increased by combination with Barkhof criteria in MRI
      (80%). CONCLUSIONS/SIGNIFICANCE: Our data indicate the relevance of CXCL13 in CIS
      to predict conversion to MS. It furthermore shows CXCL13 to be an important
      mediator in the inflammatory cascade associated with the polyspecific intrathecal
      B cell response that manifests itself in OCB and MRZR.

PMID- 20700490
TI  - Continuous attractors with morphed/correlated maps.
AB  - Continuous attractor networks are used to model the storage and representation of
      analog quantities, such as position of a visual stimulus. The storage of multiple
      continuous attractors in the same network has previously been studied in the
      context of self-position coding. Several uncorrelated maps of environments are
      stored in the synaptic connections, and a position in a given environment is
      represented by a localized pattern of neural activity in the corresponding map,
      driven by a spatially tuned input. Here we analyze networks storing a pair of
      correlated maps, or a morph sequence between two uncorrelated maps. We find a
      novel state in which the network activity is simultaneously localized in both
      maps. In this state, a fixed cue presented to the network does not determine
      uniquely the location of the bump, i.e. the response is unreliable, with neurons
      not always responding when their preferred input is present. When the tuned input
      varies smoothly in time, the neuronal responses become reliable and selective for
      the environment: the subset of neurons responsive to a moving input in one map
      changes almost completely in the other map. This form of remapping is a non
      trivial transformation between the tuned input to the network and the resulting
      tuning curves of the neurons. The new state of the network could be related to
      the formation of direction selectivity in one-dimensional environments and
      hippocampal remapping. The applicability of the model is not confined to self
      position representations; we show an instance of the network solving a simple
      delayed discrimination task.

PMID- 20700491
TI  - A simple self-maintaining metabolic system: robustness, autocatalysis,
      bistability.
AB  - A living organism must not only organize itself from within; it must also
      maintain its organization in the face of changes in its environment and
      degradation of its components. We show here that a simple (M,R)-system consisting
      of three interlocking catalytic cycles, with every catalyst produced by the
      system itself, can both establish a non-trivial steady state and maintain this
      despite continuous loss of the catalysts by irreversible degradation. As long as
      at least one catalyst is present at a sufficient concentration in the initial
      state, the others can be produced and maintained. The system shows bistability,
      because if the amount of catalyst in the initial state is insufficient to reach
      the non-trivial steady state the system collapses to a trivial steady state in
      which all fluxes are zero. It is also robust, because if one catalyst is
      catastrophically lost when the system is in steady state it can recreate the same
      state. There are three elementary flux modes, but none of them is an enzyme
      maintaining mode, the entire network being necessary to maintain the two
      catalysts.

PMID- 20700493
TI  - Probability matching as a computational strategy used in perception.
AB  - The question of which strategy is employed in human decision making has been
      studied extensively in the context of cognitive tasks; however, this question has
      not been investigated systematically in the context of perceptual tasks. The goal
      of this study was to gain insight into the decision-making strategy used by human
      observers in a low-level perceptual task. Data from more than 100 individuals who
      participated in an auditory-visual spatial localization task was evaluated to
      examine which of three plausible strategies could account for each observer's
      behavior the best. This task is very suitable for exploring this question because
      it involves an implicit inference about whether the auditory and visual stimuli
      were caused by the same object or independent objects, and provides different
      strategies of how using the inference about causes can lead to distinctly
      different spatial estimates and response patterns. For example, employing the
      commonly used cost function of minimizing the mean squared error of spatial
      estimates would result in a weighted averaging of estimates corresponding to
      different causal structures. A strategy that would minimize the error in the
      inferred causal structure would result in the selection of the most likely causal
      structure and sticking with it in the subsequent inference of location-"model
      selection." A third strategy is one that selects a causal structure in proportion
      to its probability, thus attempting to match the probability of the inferred
      causal structure. This type of probability matching strategy has been reported to
      be used by participants predominantly in cognitive tasks. Comparing these three
      strategies, the behavior of the vast majority of observers in this perceptual
      task was most consistent with probability matching. While this appears to be a
      suboptimal strategy and hence a surprising choice for the perceptual system to
      adopt, we discuss potential advantages of such a strategy for perception.

PMID- 20700492
TI  - Evolution of gene regulatory networks by fluctuating selection and intrinsic
      constraints.
AB  - Various characteristics of complex gene regulatory networks (GRNs) have been
      discovered during the last decade, e.g., redundancy, exponential indegree
      distributions, scale-free outdegree distributions, mutational robustness, and
      evolvability. Although progress has been made in this field, it is not well
      understood whether these characteristics are the direct products of selection or
      those of other evolutionary forces such as mutational biases and biophysical
      constraints. To elucidate the causal factors that promoted the evolution of
      complex GRNs, we examined the effect of fluctuating environmental selection and
      some intrinsic constraining factors on GRN evolution by using an individual-based
      model. We found that the evolution of complex GRNs is remarkably promoted by
      fixation of beneficial gene duplications under unpredictably fluctuating
      environmental conditions and that some internal factors inherent in organisms,
      such as mutational bias, gene expression costs, and constraints on expression
      dynamics, are also important for the evolution of GRNs. The results indicate that
      various biological properties observed in GRNs could evolve as a result of not
      only adaptation to unpredictable environmental changes but also non-adaptive
      processes owing to the properties of the organisms themselves. Our study
      emphasizes that evolutionary models considering such intrinsic constraining
      factors should be used as null models to analyze the effect of selection on GRN
      evolution.

PMID- 20700494
TI  - Connectivity, cycles, and persistence thresholds in metapopulation networks.
AB  - Synthesising the relationships between complexity, connectivity, and the
      stability of large biological systems has been a longstanding fundamental quest
      in theoretical biology and ecology. With the many exciting developments in modern
      network theory, interest in these issues has recently come to the forefront in a
      range of multidisciplinary areas. Here we outline a new theoretical analysis
      specifically relevant for the study of ecological metapopulations focusing
      primarily on marine systems, where subpopulations are generally connected via
      larval dispersal. Our work determines the qualitative and quantitative conditions
      by which dispersal and network structure control the persistence of a set of age
      structured patch populations. Mathematical modelling combined with a graph
      theoretic analysis demonstrates that persistence depends crucially on the
      topology of cycles in the dispersal network which tend to enhance the effect of
      larvae "returning home." Our method clarifies the impact directly due to network
      structure, but this almost by definition can only be achieved by examining the
      simplified case in which patches are identical; an assumption that we later
      relax. The methodology identifies critical migration routes, whose presence are
      vital to overall stability, and therefore should have high conservation priority.
      In contrast, "lonely links," or links in the network that do not participate in a
      cyclical component, have no impact on persistence and thus have low conservation
      priority. A number of other intriguing criteria for persistence are derived. Our
      modelling framework reveals new insights regarding the determinants of
      persistence, stability, and thresholds in complex metapopulations. In particular,
      while theoretical arguments have, in the past, suggested that increasing
      connectivity is a destabilizing feature in complex systems, this is not evident
      in metapopulation networks where connectivity, cycles, coherency, and
      heterogeneity all tend to enhance persistence. The results should be of interest
      for many other scientific contexts that make use of network theory.

PMID- 20700495
TI  - One rule to grow them all: a general theory of neuronal branching and its
      practical application.
AB  - Understanding the principles governing axonal and dendritic branching is
      essential for unravelling the functionality of single neurons and the way in
      which they connect. Nevertheless, no formalism has yet been described which can
      capture the general features of neuronal branching. Here we propose such a
      formalism, which is derived from the expression of dendritic arborizations as
      locally optimized graphs. Inspired by Ramon y Cajal's laws of conservation of
      cytoplasm and conduction time in neural circuitry, we show that this graphical
      representation can be used to optimize these variables. This approach allows us
      to generate synthetic branching geometries which replicate morphological features
      of any tested neuron. The essential structure of a neuronal tree is thereby
      captured by the density profile of its spanning field and by a single parameter,
      a balancing factor weighing the costs for material and conduction time. This
      balancing factor determines a neuron's electrotonic compartmentalization.
      Additions to this rule, when required in the construction process, can be
      directly attributed to developmental processes or a neuron's computational role
      within its neural circuit. The simulations presented here are implemented in an
      open-source software package, the "TREES toolbox," which provides a general set
      of tools for analyzing, manipulating, and generating dendritic structure,
      including a tool to create synthetic members of any particular cell group and an
      approach for a model-based supervised automatic morphological reconstruction from
      fluorescent image stacks. These approaches provide new insights into the
      constraints governing dendritic architectures. They also provide a novel
      framework for modelling and analyzing neuronal branching structures and for
      constructing realistic synthetic neural networks.

PMID- 20700496
TI  - Lysine120 interactions with p53 response elements can allosterically direct p53
      organization.
AB  - p53 can serve as a paradigm in studies aiming to figure out how allosteric
      perturbations in transcription factors (TFs) triggered by small changes in DNA
      response element (RE) sequences, can spell selectivity in co-factor recruitment.
      p53-REs are 20-base pair (bp) DNA segments specifying diverse functions. They may
      be located near the transcription start sites or thousands of bps away in the
      genome. Their number has been estimated to be in the thousands, and they all
      share a common motif. A key question is then how does the p53 protein recognize a
      particular p53-RE sequence among all the similar ones? Here, representative p53
      REs regulating diverse functions including cell cycle arrest, DNA repair, and
      apoptosis were simulated in explicit solvent. Among the major interactions
      between p53 and its REs involving Lys120, Arg280 and Arg248, the bps interacting
      with Lys120 vary while the interacting partners of other residues are less so. We
      observe that each p53-RE quarter site sequence has a unique pattern of
      interactions with p53 Lys120. The allosteric, DNA sequence-induced conformational
      and dynamic changes of the altered Lys120 interactions are amplified by the
      perturbation of other p53-DNA interactions. The combined subtle RE sequence
      specific allosteric effects propagate in the p53 and in the DNA. The resulting
      amplified allosteric effects far away are reflected in changes in the overall p53
      organization and in the p53 surface topology and residue fluctuations which play
      key roles in selective co-factor recruitment. As such, these observations suggest
      how similar p53-RE sequences can spell the preferred co-factor binding, which is
      the key to the selective gene transactivation and consequently different
      functional effects.

PMID- 20700497
TI  - Calcium signals driven by single channel noise.
AB  - Usually, the occurrence of random cell behavior is appointed to small copy
      numbers of molecules involved in the stochastic process. Recently, we
      demonstrated for a variety of cell types that intracellular Ca2+ oscillations are
      sequences of random spikes despite the involvement of many molecules in spike
      generation. This randomness arises from the stochastic state transitions of
      individual Ca2+ release channels and does not average out due to the existence of
      steep concentration gradients. The system is hierarchical due to the structural
      levels channel--channel cluster--cell and a corresponding strength of coupling.
      Concentration gradients introduce microdomains which couple channels of a cluster
      strongly. But they couple clusters only weakly; too weak to establish
      deterministic behavior on cell level. Here, we present a multi-scale modelling
      concept for stochastic hierarchical systems. It simulates active molecules
      individually as Markov chains and their coupling by deterministic diffusion.
      Thus, we are able to follow the consequences of random single molecule state
      changes up to the signal on cell level. To demonstrate the potential of the
      method, we simulate a variety of experiments. Comparisons of simulated and
      experimental data of spontaneous oscillations in astrocytes emphasize the role of
      spatial concentration gradients in Ca2+ signalling. Analysis of extensive
      simulations indicates that frequency encoding described by the relation between
      average and standard deviation of interspike intervals is surprisingly robust.
      This robustness is a property of the random spiking mechanism and not a result of
      control.

PMID- 20700498
TI  - Ontogenetic expression of sonic hedgehog in the chicken subpallium.
AB  - Sonic hedgehog (SHH) is a secreted signaling factor that is implicated in the
      molecular patterning of the central nervous system (CNS), somites, and limbs in
      vertebrates. SHH has a crucial role in the generation of ventral cell types along
      the entire rostrocaudal axis of the neural tube. It is secreted early in
      development by the axial mesoderm (prechordal plate and notochord) and the
      overlying ventral neural tube. Recent studies clarified the impact of SHH
      signaling mechanisms on dorsoventral patterning of the spinal cord, but the
      corresponding phenomena in the rostral forebrain are slightly different and more
      complex. This notably involves separate Shh expression in the preoptic part of
      the forebrain alar plate, as well as in the hypothalamic floor and basal plates.
      The present work includes a detailed spatiotemporal description of the singular
      alar Shh expression pattern in the rostral preoptic forebrain of chick embryos,
      comparing it with FoxG1, Dlx5, Nkx2.1, and Nkx2.2 mRNA expression at diverse
      stages of development. As a result of this mapping, we report a subdivision of
      the preoptic region in dorsal and ventral zones; only the dorsal part shows Shh
      expression. The positive area impinges as well upon a median septocommissural
      preoptic domain. Our study strongly suggests tangential migration of Shh-positive
      cells from the preoptic region into other subpallial domains, particularly into
      the pallidal mantle and the intermediate septum.

PMID- 20700499
TI  - We're the Same... but Different: Addressing Academic Divides in the Study of
      Brain and Behavior.
AB  - How the brain mediates behavior is a question relevant to a broad range of
      disciplines including evolutionary biology, basic neuroscience, psychiatry, and
      population health. Experiments in animals have traditionally used two distinct
      approaches to explore brain-behavior relationships; one uses naturally existing
      behavioral models while the other focuses on the creation and investigation of
      medically oriented models using existing laboratory-amenable organisms.
      Scientists using the first approach are often referred to and self identify as
      "neuroethologists," while the second category spans a variety of other sub
      disciplines but is often referred to broadly as "behavioral neuroscience."
      Despite an overall common scientific goal - the elucidation of the neural basis
      of behavior - members of these two groups often come from different scientific
      lineages, seek different sources of funding, and make their homes in different
      departments or colleges. The separation of these groups is also fostered by their
      attendance at different scientific conferences and publication records that
      reflect different journal preferences. Bridging this divide represents an
      opportunity to explore previously unanswerable questions and foster rapid
      scientific advances. This article explores the reasons for this divide and
      proposes measures that could help increase technology transfer and communication
      between these groups, potentially overcoming both physical and ideological gaps.

PMID- 20700500
TI  - The insular taste cortex contributes to odor quality coding.
AB  - Despite distinct peripheral and central pathways, stimulation of both the
      olfactory and the gustatory systems may give rise to the sensation of sweetness.
      Whether there is a common central mechanism producing sweet quality sensations or
      two discrete mechanisms associated independently with gustatory and olfactory
      stimuli is currently unknown. Here we used fMRI to determine whether odor
      sweetness is represented in the piriform olfactory cortex, which is thought to
      code odor quality, or in the insular taste cortex, which is thought to code taste
      quality. Fifteen participants sampled two concentrations of a pure sweet taste
      (sucrose), two sweet food odors (chocolate and strawberry), and two sweet floral
      odors (lilac and rose). Replicating prior work we found that olfactory
      stimulation activated the piriform, orbitofrontal and insular cortices. Of these
      regions, only the insula also responded to sweet taste. More importantly, the
      magnitude of the response to the food odors, but not to the non-food odors, in
      this region of insula was positively correlated with odor sweetness rating. These
      findings demonstrate that insular taste cortex contributes to odor quality coding
      by representing the taste-like aspects of food odors. Since the effect was
      specific to the food odors, and only food odors are experienced with taste, we
      suggest this common central mechanism develops as a function of experiencing
      flavors.

PMID- 20700501
TI  - Multiple reversal olfactory learning in honeybees.
AB  - In multiple reversal learning, animals trained to discriminate a reinforced from
      a non-reinforced stimulus are subjected to various, successive reversals of
      stimulus contingencies (e.g. A+ vs. B-, A- vs. B+, A+ vs. B-). This protocol is
      useful to determine whether or not animals "learn to learn" and solve successive
      discriminations faster (or with fewer errors) with increasing reversal
      experience. Here we used the olfactory conditioning of proboscis extension reflex
      to study how honeybees Apis mellifera perform in a multiple reversal task. Our
      experiment contemplated four consecutive differential conditioning phases
      involving the same odors (A+ vs. B- to A- vs. B+ to A+ vs. B- to A- vs. B+). We
      show that bees in which the weight of reinforced or non-reinforced stimuli was
      similar mastered the multiple olfactory reversals. Bees which failed the task
      exhibited asymmetric responses to reinforced and non-reinforced stimuli, thus
      being unable to rapidly reverse stimulus contingencies. Efficient reversers did
      not improve their successive discriminations but rather tended to generalize
      their choice to both odors at the end of conditioning. As a consequence, both
      discrimination and reversal efficiency decreased along experimental phases. This
      result invalidates a learning-to-learn effect and indicates that bees do not only
      respond to the actual stimulus contingencies but rather combine these with an
      average of past experiences with the same stimuli.

PMID- 20700502
TI  - Fifty Years of CPGs: Two Neuroethological Papers that Shaped the Course of
      Neuroscience.
AB  - Half a century ago, two independent papers that described unexpected results of
      experiments on locomotion in insects and crayfish appeared almost simultaneously.
      Together these papers demonstrated that an animal's central nervous system (CNS)
      was organized to produce behaviorally important motor output without the need for
      constant sensory feedback. These results contradicted the established line of
      thought that was based on interpretations of reflexes and ablation experiments,
      and established that in these animals the CNS contained neural circuits that
      could produce complex, periodic, multisegmental patterns of activity. These
      papers stimulated a flowering of research on central pattern-generating
      mechanisms that displaced reflex-based thinking everywhere except in medical
      physiology texts. Here we review these papers and their influence on thinking in
      the 1960s, 1970s, and today. We follow the development of ideas about central
      organization and control of expression of motor patterns, the roles of sensory
      input to central pattern-generating circuits, and integration of continuous
      sensory signals into a periodic motor system. We also review recent work on limb
      coordination that provides detailed cellular explanations of observations and
      speculations contained in those original papers.

PMID- 20700503
TI  - Checks and balances in neuromodulation.
AB  - Neuromodulators such as monoamines and peptides play important roles in
      activating and reconfiguring neural networks to allow behavioral flexibility.
      While the net effects of a neuromodulator change the network in a particular
      direction, careful studies of modulatory effects reveal multiple cases where a
      neuromodulator will activate functionally opposing mechanisms on a single neuron
      or synapse. This review gives examples of such opposing actions, focusing on the
      lobster pyloric network, and discusses their possible functional significance.
      One important action of opposing modulatory actions may be to stabilize the
      modulated state of the network, and to prevent it from being overmodulated and
      becoming non-functional.

PMID- 20700504
TI  - NK cell terminal differentiation: correlated stepwise decrease of NKG2A and
      acquisition of KIRs.
AB  - BACKGROUND: Terminal differentiation of NK cells is crucial in maintaining broad
      responsiveness to pathogens and discriminating normal cells from cells in
      distress. Although it is well established that KIRs, in conjunction with NKG2A,
      play a major role in the NK cell education that determines whether cells will end
      up competent or hyporesponsive, the events underlying the differentiation are
      still debated. METHODOLOGY/PRINCIPAL FINDINGS: A combination of complementary
      approaches to assess the kinetics of the appearance of each subset during
      development allowed us to obtain new insights into these terminal stages of
      differentiation, characterising their gene expression profiles at a pan-genomic
      level, their distinct surface receptor patterns and their prototypic effector
      functions. The present study supports the hypothesis that CD56dim cells derive
      from the CD56bright subset and suggests that NK cell responsiveness is determined
      by persistent inhibitory signals received during their education. We report here
      the inverse correlation of NKG2A expression with KIR expression and explore
      whether this correlation bestows functional competence on NK cells. We show that
      CD56dimNKG2A-KIR+ cells display the most differentiated phenotype associated to
      their unique ability to respond against HLA-E+ target cells. Importantly, after
      IL-12+IL-18 stimulation, reacquisition of NKG2A strongly correlates with IFN
      gamma production in CD56dimNKG2A- NK cells. CONCLUSIONS/SIGNIFICANCE: Together,
      these findings call for the reclassification of mature human NK cells into
      distinct subsets and support a new model, in which the NK cell differentiation
      and functional fate are based on a stepwise decrease of NKG2A and acquisition of
      KIRs.

PMID- 20700505
TI  - Exon-level transcriptome profiling in murine breast cancer reveals splicing
      changes specific to tumors with different metastatic abilities.
AB  - BACKGROUND: Breast cancer is the second most frequent type of cancer affecting
      women. We are increasingly aware that changes in mRNA splicing are associated
      with various characteristics of cancer. The most deadly aspect of cancer is
      metastasis, the process by which cancer spreads from the primary tumor to distant
      organs. However, little is known specifically about the involvement of
      alternative splicing in the formation of macroscopic metastases. Our study
      investigates transcript isoform changes that characterize tumors of different
      abilities to form growing metastases. METHODS AND FINDINGS: To identify
      alternative splicing events (ASEs) that are associated with the fully metastatic
      phenotype in breast cancer, we used Affymetrix Exon Microarrays to profile mRNA
      isoform variations genome-wide in weakly metastatic (168FARN and 4T07) and highly
      metastatic (4T1) mammary carcinomas. Statistical analysis identified significant
      expression changes in 7606 out of 155,994 (4%) exons and in 1725 out of 189,460
      (1%) intronic regions, which affect 2623 out of 16,654 (16%) genes. These changes
      correspond to putative alternative isoforms-several of which are novel-that are
      differentially expressed between tumors of varying metastatic phenotypes. Gene
      pathway analysis showed that 1224 of genes expressing alternative isoforms were
      involved in cell growth, cell interactions, cell proliferation, cell migration
      and cell death and have been previously linked to cancers and genetic disorders.
      We chose ten predicted splice variants for RT-PCR validation, eight of which were
      successfully confirmed (MED24, MFI2, SRRT, CD44, CLK1 and HNRNPH1). These include
      three novel intron retentions in CD44, a gene in which isoform variations have
      been previously associated with the metastasis of several cancers. CONCLUSION:
      Our findings reveal that various genes are differently spliced and/or expressed
      in association with the metastatic phenotype of tumor cells. Identification of
      metastasis-specific isoforms may contribute to the development of improved breast
      cancer stage identification and targeted therapies.

PMID- 20700506
TI  - MatureBayes: a probabilistic algorithm for identifying the mature miRNA within
      novel precursors.
AB  - BACKGROUND: MicroRNAs (miRNAs) are small, single stranded RNAs with a key role in
      post-transcriptional regulation of thousands of genes across numerous species.
      While several computational methods are currently available for identifying miRNA
      genes, accurate prediction of the mature miRNA remains a challenge. Existing
      approaches fall short in predicting the location of mature miRNAs but also in
      finding the functional strand(s) of miRNA precursors. METHODOLOGY/PRINCIPAL
      FINDINGS: Here, we present a computational tool that incorporates a Naive Bayes
      classifier to identify mature miRNA candidates based on sequence and secondary
      structure information of their miRNA precursors. We take into account both
      positive (true mature miRNAs) and negative (same-size non-mature miRNA sequences)
      examples to optimize sensitivity as well as specificity. Our method can
      accurately predict the start position of experimentally verified mature miRNAs
      for both human and mouse, achieving a significantly larger (often double)
      performance accuracy compared with two existing methods. Moreover, the method
      exhibits a very high generalization performance on miRNAs from two other
      organisms. More importantly, our method provides direct evidence about the
      features of miRNA precursors which may determine the location of the mature
      miRNA. We find that the triplet of positions 7, 8 and 9 from the mature miRNA end
      towards the closest hairpin have the largest discriminatory power, are relatively
      conserved in terms of sequence composition (mostly contain a Uracil) and are
      located within or in very close proximity to the hairpin loop, suggesting the
      existence of a possible recognition site for Dicer and associated proteins.
      CONCLUSIONS: This work describes a novel algorithm for identifying the start
      position of mature miRNA(s) produced by miRNA precursors. Our tool has
      significantly better (often double) performance than two existing approaches and
      provides new insights about the potential use of specific sequence/structural
      information as recognition signals for Dicer processing. Web Tool available at:
      http://mirna.imbb.forth.gr/MatureBayes.html.

PMID- 20700507
TI  - Characterization of a temperature-sensitive vertebrate clathrin heavy chain
      mutant as a tool to study clathrin-dependent events in vivo.
AB  - Clathrin and clathrin-dependent events are evolutionary conserved although it is
      believed that there are differences in the requirement for clathrin in yeast and
      higher vertebrates. Clathrin is a long-lived protein and thus, with clathrin
      knockdowns only long-term consequences of clathrin depletion can be studied.
      Here, we characterize the first vertebrate temperature-sensitive clathrin heavy
      chain mutant as a tool to investigate responses to rapid clathrin inactivation in
      higher eukaryotes. Although we created this mutant using a clathrin cryo-electron
      microscopy model and a yeast temperature-sensitive mutant as a guide, the
      resulting temperature-sensitive clathrin showed an altered phenotype compared to
      the corresponding yeast temperature-sensitive clathrin. First, it seemed to form
      stable triskelions at the non-permissive temperature although endocytosis was
      impaired under these conditions. Secondly, as a likely consequence of the stable
      triskelions at the non-permissive temperature, clathrin also localized correctly
      to its target membranes. Thirdly, we did not observe missorting of the lysosomal
      enzyme beta-glucuronidase which could indicate that the temperature-sensitive
      clathrin is still operating at the non-permissive temperature at the Golgi or,
      that, like in yeast, more than one TGN trafficking pathway exists. Fourthly, in
      contrast to yeast, actin does not appear to actively compensate in general
      endocytosis. Thus, there seem to be differences between vertebrates and yeast
      which can be studied in further detail with this newly created tool.

PMID- 20700508
TI  - Senescence is more important in the natural lives of long- than short-lived
      mammals.
AB  - BACKGROUND: Senescence has been widely detected among mammals, but its importance
      to fitness in wild populations remains controversial. According to evolutionary
      theories, senescence occurs at an age when selection is relatively weak, which in
      mammals can be predicted by adult survival rates. However, a recent analysis of
      senescence rates found more age-dependent mortalities in natural populations of
      longer lived mammal species. This has important implications to ageing research
      and for understanding the ecological relevance of senescence, yet so far these
      have not been widely appreciated. We re-address this question by comparing the
      mean and maximum life span of 125 mammal species. Specifically, we test the
      hypothesis that senescence occurs at a younger age relative to the mean natural
      life span in longer lived species. METHODOLOGY/PRINCIPAL FINDINGS: We show, using
      phylogenetically-informed generalised least squares models, a significant log-log
      relationship between mean life span, as calculated from estimates of adult
      survival for natural populations, and maximum recorded life span among mammals
      (R2=0.57, p<0.0001). This provides further support for a key prediction of
      evolutionary theories of ageing. The slope of this relationship (0.353+/-0.052
      s.e.m.), however, indicated that mammals with higher survival rates have a mean
      life span representing a greater fraction of their potential maximum life span:
      the ratio of maximum to mean life span decreased significantly from >10 in short
      lived to approximately 1.5 in long-lived mammal species.
      CONCLUSIONS/SIGNIFICANCE: We interpret the ratio of maximum to mean life span to
      be an index of the likelihood an individual will experience senescence, which
      largely determines maximum life span. Our results suggest that senescence occurs
      at an earlier age relative to the mean life span, and therefore is experienced by
      more individuals and remains under selection pressure, in long- compared to short
      lived mammals. A minimum rate of somatic degradation may ultimately limit the
      natural life span of mammals. Our results also indicate that senescence and
      modulating factors like oxidative stress are increasingly important to the
      fitness of longer lived mammals (and vice versa).

PMID- 20700509
TI  - Fluidization and resolidification of the human bladder smooth muscle cell in
      response to transient stretch.
AB  - BACKGROUND: Cells resident in certain hollow organs are subjected routinely to
      large transient stretches, including every adherent cell resident in lungs,
      heart, great vessels, gut, and bladder. We have shown recently that in response
      to a transient stretch the adherent eukaryotic cell promptly fluidizes and then
      gradually resolidifies, but mechanism is not yet understood. PRINCIPAL FINDINGS:
      In the isolated human bladder smooth muscle cell, here we applied a 10% transient
      stretch while measuring cell traction forces, elastic modulus, F-actin imaging
      and the F-actin/G-actin ratio. Immediately after a transient stretch, F-actin
      levels and cell stiffness were lower by about 50%, and traction forces were lower
      by about 70%, both indicative of prompt fluidization. Within 5 min, F-actin
      levels recovered completely, cell stiffness recovered by about 90%, and traction
      forces recovered by about 60%, all indicative of resolidification. The extent of
      the fluidization response was uninfluenced by a variety of signaling inhibitors,
      and, surprisingly, was localized to the unstretch phase of the stretch-unstretch
      maneuver in a manner suggestive of cytoskeletal catch bonds. When we applied an
      "unstretch-restretch" (transient compression), rather than a "stretch-unstretch"
      (transient stretch), the cell did not fluidize and the actin network did not
      depolymerize. CONCLUSIONS: Taken together, these results implicate extremely
      rapid actin disassembly in the fluidization response, and slow actin reassembly
      in the resolidification response. In the bladder smooth muscle cell, the
      fluidization response to transient stretch occurs not through signaling pathways,
      but rather through release of increased tensile forces that drive acute
      disassociation of actin.

PMID- 20700510
TI  - A systematic review on the diagnosis of pediatric bacterial pneumonia: when gold
      is bronze.
AB  - BACKGROUND: In developing countries, pneumonia is one of the leading causes of
      death in children under five years of age and hence timely and accurate diagnosis
      is critical. In North America, pneumonia is also a common source of childhood
      morbidity and occasionally mortality. Clinicians traditionally have used the
      chest radiograph as the gold standard in the diagnosis of pneumonia, but they are
      becoming increasingly aware that it is not ideal. Numerous studies have shown
      that chest radiography findings lack precision in defining the etiology of
      childhood pneumonia. There is no single test that reliably distinguishes
      bacterial from non-bacterial causes. These factors have resulted in clinicians
      historically using a combination of physical signs and chest radiographs as a
      'gold standard', though this combination of tests has been shown to be imperfect
      for diagnosis and assigning treatment. The objectives of this systematic review
      are to: 1) identify and categorize studies that have used single or multiple
      tests as a gold standard for assessing accuracy of other tests, and 2) given the
      'gold standard' used, determine the accuracy of these other tests for diagnosing
      childhood bacterial pneumonia. METHODS AND FINDINGS: Search strategies were
      developed using a combination of subject headings and keywords adapted for 18
      electronic bibliographic databases from inception to May 2008. Published studies
      were included if they: 1) included children one month to 18 years of age, 2)
      provided sufficient data regarding diagnostic accuracy to construct a 2x2 table,
      and 3) assessed the accuracy of one or more index tests as compared with other
      test(s) used as a 'gold standard'. The literature search revealed 5,989
      references of which 256 were screened for inclusion, resulting in 25 studies that
      satisfied all inclusion criteria. The studies examined a range of bacterium types
      and assessed the accuracy of several combinations of diagnostic tests. Eleven
      different gold standards were studied in the 25 included studies. Criterion
      validity was calculated for fourteen different index tests using eleven different
      gold standards. The most common gold standard utilized was blood culture tests
      used in six studies. Fourteen different tests were measured as index tests. PCT
      was the most common measured in five studies each with a different gold standard.
      CONCLUSIONS: We have found that studies assessing the diagnostic accuracy of
      clinical, radiological, and laboratory tests for bacterial childhood pneumonia
      have used a heterogeneous group of gold standards, and found, at least in part
      because of this, that index tests have widely different accuracies. These
      findings highlight the need for identifying a widely accepted gold standard for
      diagnosis of bacterial pneumonia in children.

PMID- 20700511
TI  - Plant species loss affects life-history traits of aphids and their parasitoids.
AB  - The consequences of plant species loss are rarely assessed in a multi-trophic
      context and especially effects on life-history traits of organisms at higher
      trophic levels have remained largely unstudied. We used a grassland biodiversity
      experiment and measured the effects of two components of plant diversity, plant
      species richness and the presence of nitrogen-fixing legumes, on several life
      history traits of naturally colonizing aphids and their primary and secondary
      parasitoids in the field. We found that, irrespective of aphid species identity,
      the proportion of winged aphid morphs decreased with increasing plant species
      richness, which was correlated with decreasing host plant biomass. Similarly,
      emergence proportions of parasitoids decreased with increasing plant species
      richness. Both, emergence proportions and proportions of female parasitoids were
      lower in plots with legumes, where host plants had increased nitrogen
      concentrations. This effect of legume presence could indicate that aphids were
      better defended against parasitoids in high-nitrogen environments. Body mass of
      emerged individuals of the two most abundant primary parasitoid species was,
      however, higher in plots with legumes, suggesting that once parasitoids could
      overcome aphid defenses, they could profit from larger or more nutritious hosts.
      Our study demonstrates that cascading effects of plant species loss on higher
      trophic levels such as aphids, parasitoids and secondary parasitoids begin with
      changed life-history traits of these insects. Thus, life-history traits of
      organisms at higher trophic levels may be useful indicators of bottom-up effects
      of plant diversity on the biodiversity of consumers.

PMID- 20700513
TI  - Maladaptive behaviors are linked with inefficient sleep in individuals with
      developmental disabilities.
AB  - The purpose of the current study was to assess the relations between nightly
      sleep patterns and the frequency of daily maladaptive behavior. Antecedent and
      consequential relations between sleep patterns and behavior were evaluated with
      time series analysis. Sleep efficiency and maladaptive behavior were determined
      for 20 female residents of an institutional care facility for adults with
      developmental disabilities. Daily maladaptive behavioral data and nightly
      sleep/awake logs were collected for 4 months for each participant. Efficient
      sleep patterns were significantly associated with lower frequencies of
      maladaptive behaviors. All lagged cross-correlations 8 days before and 8 days
      after an evening of sleep were significant. These findings suggested that
      inefficient sleep was associated with increased maladaptive behaviors and that
      the lagged associations reflected a chronic but not an acute linkage between
      sleep and behavior.

PMID- 20700512
TI  - r84, a novel therapeutic antibody against mouse and human VEGF with potent anti
      tumor activity and limited toxicity induction.
AB  - Vascular endothelial growth factor (VEGF) is critical for physiological and
      pathological angiogenesis. Within the tumor microenvironment, VEGF functions as
      an endothelial cell survival factor, permeability factor, mitogen, and
      chemotactic agent. The majority of these functions are mediated by VEGF-induced
      activation of VEGF receptor 2 (VEGFR2), a high affinity receptor tyrosine kinase
      expressed by endothelial cells and other cell types in the tumor
      microenvironment. VEGF can also ligate other cell surface receptors including
      VEGFR1 and neuropilin-1 and -2. However, the importance of VEGF-induced
      activation of these receptors in tumorigenesis is still unclear. We report the
      development and characterization of r84, a fully human monoclonal antibody that
      binds human and mouse VEGF and selectively blocks VEGF from interacting with
      VEGFR2 but does not interfere with VEGF:VEGFR1 interaction. Selective blockade of
      VEGF binding to VEGFR2 by r84 is shown through ELISA, receptor binding assays,
      receptor activation assays, and cell-based functional assays. Furthermore, we
      show that r84 has potent anti-tumor activity and does not alter tissue histology
      or blood and urine chemistry after chronic high dose therapy in mice. In
      addition, chronic r84 therapy does not induce elevated blood pressure levels in
      some models. The ability of r84 to specifically block VEGF:VEGFR2 binding
      provides a valuable tool for the characterization of VEGF receptor pathway
      activation during tumor progression and highlights the utility and safety of
      selective blockade of VEGF-induced VEGFR2 signaling in tumors.

PMID- 20700514
TI  - From open radical hysterectomy to robot-assisted laparoscopic radical
      hysterectomy for early stage cervical cancer: aspects of a single institution
      learning curve.
AB  - We analysed the introduction of the robot-assisted laparoscopic radical
      hysterectomy in patients with early-stage cervical cancer with respect to patient
      benefits and surgeon-related aspects of a surgical learning curve. A
      retrospective review of the first 14 robot-assisted laparoscopic radical
      hysterectomies and the last 14 open radical hysterectomies in a similar clinical
      setting with the same surgical team was conducted. Patients were candidates for a
      laparoscopic sentinel node procedure, pelvic lymph node dissection and open
      radical hysterectomy (RH) before August 2006 and were candidates for a
      laparoscopic sentinel node procedure, pelvic lymph node dissection and robot
      assisted laparoscopic radical hysterectomy (RALRH) after August 2006. Overall,
      blood loss in the open cases was significantly more compared with the robot
      cases. Median hospital stay after RALRH was 5 days less than after RH. The median
      theatre time in the learning period for the robot procedure was reduced from 9 h
      to less that 4 h and compared well to the 3 h and 45 min for an open procedure.
      Three complications occurred in the open group and one in the robot group. RALRH
      is feasible and of benefit to the patient with early stage cervical cancer by a
      reduction of blood loss and reduced hospital stay. Introduction of this new
      technique requires a learning curve of less than 15 cases that will reduce the
      operating time to a level comparable to open surgery.

PMID- 20700515
TI  - Variability of Quality of Life at Small Scales: Addis Ababa, Kirkos Sub-City.
AB  - Urban quality of life (QoL) is becoming a subject of urban research mainly for
      western and Asian countries. Such attention is due to an increasing awareness of
      the contribution of QoL studies in identifying intervention areas and in
      monitoring urban planning policies. However, most studies are carried out at city
      or country level that can average out details at small scales. In this paper we
      present a case study where the urban QoL at small scale is measured and its
      variability is evaluated for Kirkos sub-city of Addis Ababa, Ethiopia. The study
      is based on data from a household survey and some secondary data. Geographic
      information system (GIS) is applied to extract proximity information (e.g.,
      distance to school facilities) and visualize the spatial distribution of QoL.
      Statistical methods such as factor analysis are applied to establish an index of
      objective QoL while coefficient of variation is applied to evaluate spatial
      variability of subjective QoL. The results of this study reveal that the
      subjective quality of life (QoL) scores show large variation in the sub-city. The
      mean QoL score also indicates that the respondents in the sub-city, on average,
      are dissatisfied with the quality of their life. Respondents with higher
      education level and income are on average, however, more satisfied with their QoL
      in the sub-city. The results reveal that the lower the QoL in the Kebele, the
      larger the variability of QoL within the Kebele. Such indicates how aggregation
      at large scale can average out the variation of QoL at small scales. The results
      reveal the presence of QoL variability at small scales. The comparison between
      the subjective and the objective QoL at Kebele level indicated a state of
      dissonance, adaptation, deprivation or well-being. Such results suggest that the
      two measures do not always indicate the same level of QoL.

PMID- 20700517
TI  - Child Poverty in Vietnam: Providing Insights Using a Country-Specific and
      Multidimensional Model.
AB  - Despite a wide under-prioritization, the issue of child poverty has received
      increasing attention worldwide over the last decade. The acknowledgement in
      Vietnam that child-specific poverty measurement is crucial for poverty efforts
      directed towards children, and the current lack thereof, instigated the
      development of a Vietnam child poverty approach. This paper proposes a country
      specific, multidimensional and outcome-based approach for the measurement of the
      incidence, depth and severity of child poverty. It does so at the level of the
      individual child using household survey data. The development of such an approach
      at the level of the individual child presents an appropriate alternative for or
      supplement to the widely used monetary poverty approach, allowing for the use of
      compatible analytical methods. Findings suggest that 37% of all children in
      Vietnam live in poverty, with the most pressing areas of deprivation being water,
      sanitation and leisure. We do not find evidence for a gender bias but do observe
      a large urban-rural divide, regional disparities and large ethnic inequalities.
      We argue that this tailor-made approach is a valuable new tool for policy makers
      and analysts in Vietnam as it enables identification and analysis of poor
      children, their characteristics and most pressing areas of deprivation within the
      country's specific social and cultural context.

PMID- 20700516
TI  - Does bilateral damage to the human amygdala produce autistic symptoms?
AB  - A leading neurological hypothesis for autism postulates amygdala dysfunction.
      This hypothesis has considerable support from anatomical and neuroimaging
      studies. Individuals with bilateral amygdala lesions show impairments in some
      aspects of social cognition. These impairments bear intriguing similarity to
      those reported in people with autism, such as impaired recognition of emotion in
      faces, impaired theory of mind abilities, failure to fixate eyes in faces, and
      difficulties in regulating personal space distance to others. Yet such
      neurological cases have never before been assessed directly to see if they meet
      criteria for autism spectrum disorders (ASD). Here we undertook such an
      investigation in two rare participants with developmental-onset bilateral
      amygdala lesions. We administered a comprehensive clinical examination, as well
      as the Autism Diagnostic Observation Schedule (ADOS), the Social Responsiveness
      Scale (SRS), together with several other standardized questionnaires. Results
      from the two individuals with amygdala lesions were compared with published norms
      from both healthy populations as well as from people with ASD. Neither
      participant with amygdala lesions showed any evidence of autism across the array
      of different measures. The findings demonstrate that amygdala lesions in
      isolation are not sufficient for producing autistic symptoms. We suggest instead
      that it may be abnormal connectivity between the amygdala and other structures
      that contributes to autistic symptoms at a network level.

PMID- 20700518
TI  - Safe total intrafascial laparoscopic (TAIL) hysterectomy: a prospective cohort
      study.
AB  - This study directly compares total intrafascial laparoscopic (TAIL) hysterectomy
      with vaginal (VH) and abdominal (AH) hysterectomy with regard to safety,
      operating time and time of convalescence. The study is a prospective cohort study
      (Canadian Task Force classification II-2), including data from patients of a
      single university-affiliated teaching institution, admitted between 1997 and 2008
      for hysterectomy due to benign uterus pathology. Patient data were collected pre
      , intra- and postoperatively and complications documented using a standardised
      data sheet of a Swiss obstetric and gynaecological study group
      (Arbeitsgemeinschaft Schweizerische Frauenkliniken, Amlikon/Switzerland).
      Classification of complications (major complications and minor complications) for
      all three operation techniques, evaluation of surgeons and comparison of
      operation times and days of hospitalisation were analysed. 3066 patients were
      included in this study. 993 patients underwent AH, 642 VH and 1,431 total
      intrafascial hysterectomy. No statistically significant difference for the
      operation times comparing the three groups can be demonstrated. The mean hospital
      stay in the TAIL hysterectomy, VH and AH groups is 5.8 +/- 2.4, 8.8 +/- 4.0 and
      10.4 +/- 3.9 days, respectively. The postoperative minor complications including
      infection rates are low in the TAIL hysterectomy group (3.8%) when compared with
      either the AH group (15.3%) or the VH group (11.2%), respectively. The total of
      minor complications is statistically significant lower for TAIL hysterectomy as
      for AH (O.R. 4.52, CI 3.25-6.31) or VH (O.R. 3.16, CI 2.16-4.62). Major
      haemorrhage with consecutive reoperation is observed statistically significantly
      more frequent in the AH group when compared to the TAIL hysterectomy group, with
      an O.R. of 6.13 (CI 3.05-12.62). Overall, major intra- and postoperative
      complications occur significant more frequently in the AH group (8.6%) when
      compared to the VH group (3%) and the TAIL hysterectomy group (1.8%). The
      incidence of major complications applying the standardised TAIL hysterectomy
      technique is not related to the experience of the surgeons. We conclude that a
      standardised intrafascial technique of total laparoscopic (TAIL) hysterectomy
      using an anatomically developed special uterine device is associated with a very
      low incidence of minor and major intra- and postoperative complications. The
      direct comparison of complication rates with either vaginal or abdominal
      hysterectomy favours the total laparoscopic technique, and therefore, this
      technique can be recommended as a relatively atraumatic procedure. The operation
      times are comparable for all three techniques without any statistically
      significant differences. This technique for laparoscopic hysterectomy is shown to
      be equally safe when applied by experienced gynaecologic surgeons or by residents
      in training. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this
      article (doi:10.1007/s10397-010-0569-0) contains supplementary material, which is
      available to authorized users.

PMID- 20700519
TI  - Hysterectomy or a minimal invasive alternative? A systematic review on quality of
      life and satisfaction.
AB  - Nowadays, an increasing number of minimal invasive treatment alternatives to
      hysterectomy may be offered to the patient. In determining the appropriate
      treatment option, the patient has a distinct dilemma if a minimal invasive
      treatment with lesser effect than hysterectomy should be chosen or if a
      hysterectomy should be chosen which is a major surgery and requires longer
      recovery than the minimal invasive alternative. Quality-of-life (QoL)
      questionnaires that take subjective health perception into account are currently
      used to assess the treatment effects. The objective of this literature study is
      to determine and discuss the role of QoL as an outcome in randomized controlled
      trials (RCT) or systematic reviews of RCTs that study the treatment effect of
      hysterectomy compared to that of minimal invasive alternatives. A systematic
      literature search was performed in the PubMed database and in the Cochrane
      database to find randomized trials and systematic reviews of randomized trials,
      comparing hysterectomy with minimal invasive or conservative treatment options
      with sufficient follow-up using satisfaction, health status, and quality of life
      as outcomes. The results were based on nine randomized trials and two systematic
      reviews. The differences are mostly in favor of hysterectomy. In two out of four
      studied treatment alternatives, the satisfaction or health status is different in
      favor of hysterectomy while the QoL is equivalent. After 2 years of follow-up,
      differences between both groups have disappeared, possibly because of the
      crossover effect. Possible reasons for the lesser response of QoL compared to
      satisfaction or health status are discussed. The fundamental question if patients
      have a better quality of life at all times if they choose for a minimal invasive
      alternative of hysterectomy remains unresolved. Information, individualization,
      and freedom of choice before surgery probably best serve the sense of well being
      and quality of life thereafter.

PMID- 20700520
TI  - Wavelet packets-based blind watermarking for medical image management.
AB  - The last decade has witnessed an explosive use of medical images and Electronics
      Patient Record (EPR) in the healthcare sector for facilitating the sharing of
      patient information and exchange between networked hospitals and healthcare
      centers. To guarantee the security, authenticity and management of medical images
      and information through storage and distribution, the watermarking techniques are
      growing to protect the medical healthcare information. This paper presents a
      technique for embedding the EPR information in the medical image to save storage
      space and transmission overheads and to guarantee security of the shared data. In
      this paper a new method for protecting the patient information in which the
      information is embedded as a watermark in the discrete wavelet packet transform
      (DWPT) of the medical image using the hospital logo as a reference image. The
      patient information is coded by an error correcting code (ECC), BCH code, to
      enhance the robustness of the proposed method. The scheme is blind so that the
      EPR can be extracted from the medical image without the need of the original
      image. Therefore, this proposed technique is useful in telemedicine applications.
      Performance of the proposed method was tested using four modalities of medical
      images; MRA, MRI, Radiological, and CT. Experimental results showed no visible
      difference between the watermarked and the original image. Moreover, the proposed
      watermarking method is robust against a wide range of attacks such as JPEG
      coding, Gaussian noise addition, histogram equalization, gamma correction,
      contrast adjustment, and sharpen filter and rotation.

PMID- 20700521
TI  - The influence of psychological state and motivation on brain-computer interface
      performance in patients with amyotrophic lateral sclerosis - a longitudinal
      study.
AB  - The current study investigated the effects of psychological well-being measured
      as quality of life (QoL), depression, current mood and motivation on brain
      computer interface (BCI) performance in amyotrophic lateral sclerosis (ALS). Six
      participants with most advanced ALS were trained either for a block of 20
      sessions with a BCI based on sensorimotor rhythms (SMR) or a block of 10 sessions
      with a BCI based on event-related potentials, or both. Questionnaires assessed
      QoL and severity of depressive symptoms before each training block and mood and
      motivation before each training session. The SMR-BCI required more training than
      the P300-BCI. The information transfer rate was higher with the P300-BCI (3.25
      bits/min) than with the SMR-BCI (1.16 bits/min). Mood and motivation were related
      to the number of BCI sessions. Motivational factors, specifically challenge and
      mastery confidence, were positively related to BCI performance (controlled for
      the number of sessions) in tow participants, while incompetence fear was
      negatively related with performance in one participant. BCI performance was not
      related to motivational factors in three other participants nor to mood in any of
      the six participants. We conclude that motivational factors may be related to BCI
      performance in individual subjects and suggest that motivational factors and well
      being should be assessed in standard BCI protocols. We also recommend using P300
      based BCI as first choice in severely paralyzed patients who present with a P300
      evoked potential.

PMID- 20700522
TI  - Sucrose acceptance and different forms of associative learning of the honey bee
      (apis mellifera L.) in the field and laboratory.
AB  - The experiments analyze different forms of learning and 24-h retention in the
      field and in the laboratory in bees that accept sucrose with either low (</=3%)
      or high (>/=30% or >/=50%) concentrations. In the field we studied color learning
      at a food site and at the hive entrance. In the laboratory olfactory conditioning
      of the proboscis extension response (PER) was examined. In the color learning
      protocol at a feeder, bees with low sucrose acceptance thresholds (</=3%) show
      significantly faster and better acquisition than bees with high thresholds
      (>/=50%). Retention after 24 h is significantly different between the two groups
      of bees and the choice reactions converge. Bees with low and high acceptance
      thresholds in the field show no differences in the sucrose sensitivity PER tests
      in the laboratory. Acceptance thresholds in the field are thus a more sensitive
      behavioral measure than PER responsiveness in the laboratory. Bees with low
      acceptance thresholds show significantly better acquisition and 24-h retention in
      olfactory learning in the laboratory compared to bees with high thresholds. In
      the learning protocol at the hive entrance bees learn without sucrose reward that
      a color cue signals an open entrance. In this experiment, bees with high sucrose
      acceptance thresholds showed significantly better learning and reversal learning
      than bees with low thresholds. These results demonstrate that sucrose acceptance
      thresholds affect only those forms of learning in which sucrose serves as the
      reward. The results also show that foraging behavior in the field is a good
      predictor for learning behavior in the field and in the laboratory.

PMID- 20700523
TI  - Environmental enrichment induces behavioral recovery and enhanced hippocampal
      cell proliferation in an antidepressant-resistant animal model for PTSD.
AB  - BACKGROUND: Post traumatic stress disorder (PTSD) can be considered the result of
      a failure to recover after a traumatic experience. Here we studied possible
      protective and therapeutic aspects of environmental enrichment (with and without
      a running wheel) in Sprague Dawley rats exposed to an inescapable foot shock
      procedure (IFS). METHODOLOGY/PRINCIPAL FINDINGS: IFS induced long-lasting
      contextual and non-contextual anxiety, modeling some aspects of PTSD. Even 10
      weeks after IFS the rats showed reduced locomotion in an open field. The
      antidepressants imipramine and escitalopram did not improve anxiogenic behavior
      following IFS. Also the histone deacetylase (HDAC) inhibitor sodium butyrate did
      not alleviate the IFS induced immobility. While environmental enrichment (EE)
      starting two weeks before IFS did not protect the animals from the behavioral
      effects of the shocks, exposure to EE either immediately after the shock or one
      week later induced complete recovery three weeks after IFS. In the next set of
      experiments a running wheel was added to the EE to enable voluntary exercise
      (EE/VE). This also led to reduced anxiety. Importantly, this behavioral recovery
      was not due to a loss of memory for the traumatic experience. The behavioral
      recovery correlated with an increase in cell proliferation in hippocampus, a
      decrease in the tissue levels of noradrenalin and increased turnover of 5-HT in
      prefrontal cortex and hippocampus. CONCLUSIONS/SIGNIFICANCE: This animal study
      shows the importance of (physical) exercise in the treatment of psychiatric
      diseases, including post-traumatic stress disorder and points out the possible
      role of EE in studying the mechanism of recovery from anxiety disorders.

PMID- 20700524
TI  - Dual beneficial effects of (-)-epigallocatechin-3-gallate on levodopa methylation
      and hippocampal neurodegeneration: in vitro and in vivo studies.
AB  - BACKGROUND: A combination of levodopa (L-DOPA) and carbidopa is the most commonly
      used treatment for symptom management in Parkinson's disease. Studies have shown
      that concomitant use of a COMT inhibitor is highly beneficial in controlling the
      wearing-off phenomenon by improving L-DOPA bioavailability as well as brain
      entry. The present study sought to determine whether (-)-epigallocatechin-3
      gallate (EGCG), a common tea polyphenol, can serve as a naturally-occurring COMT
      inhibitor that also possesses neuroprotective actions. METHODOLOGY/PRINCIPAL
      FINDINGS: Using both in vitro and in vivo models, we investigated the modulating
      effects of EGCG on L-DOPA methylation as well as on chemically induced oxidative
      neuronal damage and degeneration. EGCG strongly inhibited human liver COMT
      mediated O-methylation of L-DOPA in a concentration-dependent manner in vitro,
      with an average IC50 of 0.36 microM. Oral administration of EGCG moderately
      lowered the accumulation of 3-O-methyldopa in the plasma and striatum of rats
      treated with L-DOPA+carbidopa. In addition, EGCG also reduced glutamate-induced
      oxidative cytotoxicity in cultured HT22 mouse hippocampal neuronal cells through
      inactivation of the nuclear factor kappaB-signaling pathway. Under in vivo
      conditions, administration of EGCG exerted a strong protective effect against
      kainic acid-induced oxidative neuronal death in the hippocampus of rats.
      CONCLUSIONS/SIGNIFICANCE: These observations suggest that oral administration of
      EGCG may have significant beneficial effects in Parkinson's patients treated with
      L-DOPA and carbidopa by exerting a modest inhibition of L-DOPA methylation plus a
      strong neuroprotection against oxidative damage and degeneration.

PMID- 20700525
TI  - Attraction basins as gauges of robustness against boundary conditions in
      biological complex systems.
AB  - One fundamental concept in the context of biological systems on which researches
      have flourished in the past decade is that of the apparent robustness of these
      systems, i.e., their ability to resist to perturbations or constraints induced by
      external or boundary elements such as electromagnetic fields acting on neural
      networks, micro-RNAs acting on genetic networks and even hormone flows acting
      both on neural and genetic networks. Recent studies have shown the importance of
      addressing the question of the environmental robustness of biological networks
      such as neural and genetic networks. In some cases, external regulatory elements
      can be given a relevant formal representation by assimilating them to or modeling
      them by boundary conditions. This article presents a generic mathematical
      approach to understand the influence of boundary elements on the dynamics of
      regulation networks, considering their attraction basins as gauges of their
      robustness. The application of this method on a real genetic regulation network
      will point out a mathematical explanation of a biological phenomenon which has
      only been observed experimentally until now, namely the necessity of the presence
      of gibberellin for the flower of the plant Arabidopsis thaliana to develop
      normally.

PMID- 20700526
TI  - Mutation K42R in ribosomal protein S12 does not affect susceptibility of
      Mycobacterium smegmatis 16S rRNA A-site mutants to 2-deoxystreptamines.
AB  - Recent studies have suggested that ribosomal protein S12 modulates 16S rRNA
      function and susceptibility to 2-deoxystreptamine aminoglycosides. To study
      whether the non-restrictive K42R mutation in RpsL affects 2-deoxystreptamine
      susceptibility in Mycobacterium smegmatis, we studied the drug susceptibility
      pattern of various mutants with genetic alterations in the 16S rRNA decoding A
      site in the context of wild-type and mutant protein S12. RpsL K42R substitution
      was found not to affect the drug resistance pattern associated with mutational
      alterations in 16S rRNA H44.

PMID- 20700527
TI  - Able-bodied wild chimpanzees imitate a motor procedure used by a disabled
      individual to overcome handicap.
AB  - Chimpanzee culture has generated intense recent interest, fueled by the technical
      complexity of chimpanzee tool-using traditions; yet it is seriously doubted
      whether chimpanzees are able to learn motor procedures by imitation under natural
      conditions. Here we take advantage of an unusual chimpanzee population as a
      'natural experiment' to identify evidence for imitative learning of this kind in
      wild chimpanzees. The Sonso chimpanzee community has suffered from high levels of
      snare injury and now has several manually disabled members. Adult male Tinka,
      with near-total paralysis of both hands, compensates inability to scratch his
      back manually by employing a distinctive technique of holding a growing liana
      taut while making side-to-side body movements against it. We found that seven
      able-bodied young chimpanzees also used this 'liana-scratch' technique, although
      they had no need to. The distribution of the liana-scratch technique was
      statistically associated with individuals' range overlap with Tinka and the
      extent of time they spent in parties with him, confirming that the technique is
      acquired by social learning. The motivation for able-bodied chimpanzees copying
      his variant is unknown, but the fact that they do is evidence that the imitative
      learning of motor procedures from others is a natural trait of wild chimpanzees.

PMID- 20700528
TI  - Biogeography and potential exchanges among the atlantic Equatorial belt cold-seep
      faunas.
AB  - Like hydrothermal vents along oceanic ridges, cold seeps are patchy and isolated
      ecosystems along continental margins, extending from bathyal to abyssal depths.
      The Atlantic Equatorial Belt (AEB), from the Gulf of Mexico to the Gulf of
      Guinea, was one focus of the Census of Marine Life ChEss (Chemosynthetic
      Ecosystems) program to study biogeography of seep and vent fauna. We present a
      review and analysis of collections from five seep regions along the AEB: the Gulf
      of Mexico where extensive faunal sampling has been conducted from 400 to 3300 m,
      the Barbados accretionary prism, the Blake ridge diapir, and in the Eastern
      Atlantic from the Congo and Gabon margins and the recently explored Nigeria
      margin. Of the 72 taxa identified at the species level, a total of 9 species or
      species complexes are identified as amphi-Atlantic. Similarity analyses based on
      both Bray Curtis and Hellinger distances among 9 faunal collections, and
      principal component analysis based on presence/absence of megafauna species at
      these sites, suggest that within the AEB seep megafauna community structure is
      influenced primarily by depth rather than by geographic distance. Depth
      segregation is observed between 1000 and 2000 m, with the middle slope sites
      either grouped with those deeper than 2000 m or with the shallower sites. The
      highest level of community similarity was found between the seeps of the Florida
      escarpment and Congo margin. In the western Atlantic, the highest degree of
      similarity is observed between the shallowest sites of the Barbados prism and of
      the Louisiana slope. The high number of amphi-atlantic cold-seep species that do
      not cluster according to biogeographic regions, and the importance of depth in
      structuring AEB cold-seep communities are the major conclusions of this study.
      The hydrothermal vent sites along the Mid Atlantic Ridge (MAR) did not appear as
      "stepping stones" for dispersal of the AEB seep fauna, however, the south MAR and
      off axis regions should be further explored to more fully test this hypothesis.

PMID- 20700529
TI  - Calcineurin interacts with PERK and dephosphorylates calnexin to relieve ER
      stress in mammals and frogs.
AB  - BACKGROUND: The accumulation of misfolded proteins within the endoplasmic
      reticulum (ER) triggers a cellular process known as the Unfolded Protein Response
      (UPR). One of the earliest responses is the attenuation of protein translation.
      Little is known about the role that Ca2+ mobilization plays in the early UPR.
      Work from our group has shown that cytosolic phosphorylation of calnexin (CLNX)
      controls Ca2+ uptake into the ER via the sarco-endoplasmic reticulum Ca2+-ATPase
      (SERCA) 2b. METHODOLOGY/PRINCIPAL FINDINGS: Here, we demonstrate that calcineurin
      (CN), a Ca2+ dependent phosphatase, associates with the (PKR)-like ER kinase
      (PERK), and promotes PERK auto-phosphorylation. This association, in turn,
      increases the phosphorylation level of eukaryotic initiation factor-2 alpha (eIF2
      alpha) and attenuates protein translation. Data supporting these conclusions were
      obtained from co-immunoprecipitations, pull-down assays, in-vitro kinase assays,
      siRNA treatments and [35S]-methionine incorporation measurements. The interaction
      of CN with PERK was facilitated at elevated cytosolic Ca2+ concentrations and
      involved the cytosolic domain of PERK. CN levels were rapidly increased by ER
      stressors, which could be blocked by siRNA treatments for CN-Aalpha in cultured
      astrocytes. Downregulation of CN blocked subsequent ER-stress-induced increases
      in phosphorylated elF2-alpha. CN knockdown in Xenopus oocytes predisposed them to
      induction of apoptosis. We also found that CLNX was dephosphorylated by CN when
      Ca2+ increased. These data were obtained from [gamma32P]-CLNX
      immunoprecipitations and Ca2+ imaging measurements. CLNX was dephosphorylated
      when Xenopus oocytes were treated with ER stressors. Dephosphorylation was
      pharmacologically blocked by treatment with CN inhibitors. Finally, evidence is
      presented that PERK phosphorylates CN-A at low resting levels of Ca2+. We further
      show that phosphorylated CN-A exhibits decreased phosphatase activity, consistent
      with this regulatory mechanism being shut down as ER homeostasis is re
      established. CONCLUSIONS/SIGNIFICANCE: Our data suggest two new complementary
      roles for CN in the regulation of the early UPR. First, CN binding to PERK
      enhances inhibition of protein translation to allow the cell time to recover. The
      induction of the early UPR, as indicated by increased P-elF2alpha, is critically
      dependent on a translational increase in CN-Aalpha. Second, CN dephosphorylates
      CLNX and likely removes inhibition of SERCA2b activity, which would aid the rapid
      restoration of ER Ca2+ homeostasis.

PMID- 20700530
TI  - Large-scale absence of sharks on reefs in the greater-Caribbean: a footprint of
      human pressures.
AB  - BACKGROUND: In recent decades, large pelagic and coastal shark populations have
      declined dramatically with increased fishing; however, the status of sharks in
      other systems such as coral reefs remains largely unassessed despite a long
      history of exploitation. Here we explore the contemporary distribution and
      sighting frequency of sharks on reefs in the greater-Caribbean and assess the
      possible role of human pressures on observed patterns. METHODOLOGY/PRINCIPAL
      FINDINGS: We analyzed 76,340 underwater surveys carried out by trained volunteer
      divers between 1993 and 2008. Surveys were grouped within one km2 cells, which
      allowed us to determine the contemporary geographical distribution and sighting
      frequency of sharks. Sighting frequency was calculated as the ratio of surveys
      with sharks to the total number of surveys in each cell. We compared sighting
      frequency to the number of people in the cell vicinity and used population
      viability analyses to assess the effects of exploitation on population trends.
      Sharks, with the exception of nurse sharks occurred mainly in areas with very low
      human population or strong fishing regulations and marine conservation.
      Population viability analysis suggests that exploitation alone could explain the
      large-scale absence; however, this pattern is likely to be exacerbated by
      additional anthropogenic stressors, such as pollution and habitat degradation,
      that also correlate with human population. CONCLUSIONS/SIGNIFICANCE: Human
      pressures in coastal zones have lead to the broad-scale absence of sharks on
      reefs in the greater-Caribbean. Preventing further loss of sharks requires urgent
      management measures to curb fishing mortality and to mitigate other anthropogenic
      stressors to protect sites where sharks still exist. The fact that sharks still
      occur in some densely populated areas where strong fishing regulations are in
      place indicates the possibility of success and encourages the implementation of
      conservation measures.

PMID- 20700531
TI  - The association of alcohol and alcohol metabolizing gene variants with diabetes
      and coronary heart disease risk factors in a white population.
AB  - BACKGROUND: Epidemiological studies have shown a J- or U-shaped relation between
      alcohol and type 2 diabetes and coronary heart disease (CHD). The underlying
      mechanisms are not clear. The aim was to examine the association between alcohol
      intake and diabetes and intermediate CHD risk factors in relation to selected ADH
      and ALDH gene variants. METHODOLOGY/PRINCIPAL FINDINGS: Cross-sectional study
      including 6,405 Northern European men and women aged 30-60 years from the general
      population of Copenhagen, Denmark. Data were collected with self-administered
      questionnaires, a physical examination, a 2 hour oral glucose tolerance test, and
      various blood tests. J shaped associations were observed between alcohol and
      diabetes, metabolic syndrome (MS), systolic and diastolic blood pressure,
      triglyceride, total cholesterol, and total homocysteine. Positive associations
      were observed with insulin sensitivity and HDL cholesterol, and a negative
      association with insulin release. Only a few of the selected ADH and ALDH gene
      variants was observed to have an effect. The ADH1c (rs1693482) fast metabolizing
      CC genotype was associated with an increased risk of impaired glucose tolerance
      (IGT)/diabetes compared to the CT and TT genotypes. Significant interactions were
      observed between alcohol and ADH1b (rs1229984) with respect to LDL and between
      alcohol and ALDH2 (rs886205) with respect to IGT/diabetes.
      CONCLUSIONS/SIGNIFICANCE: The selected ADH and ALDH gene variants had only minor
      effects, and did not seem to markedly modify the health effects of alcohol
      drinking. The observed statistical significant associations would not be
      significant, if corrected for multiple testing.

PMID- 20700532
TI  - Expression and function of variants of human catecholamine transporters lacking
      the fifth transmembrane region encoded by exon 6.
AB  - BACKGROUND: The transporters for dopamine (DAT) and norepinephrine (NET) are
      members of the Na+- and Cl--dependent neurotransmitter transporter family SLC6.
      There is a line of evidence that alternative splicing results in several isoforms
      of neurotransmitter transporters including NET. However, its relevance to the
      physiology and pathology of the neurotransmitter reuptake system has not been
      fully elucidated. METHODOLOGY/PRINCIPAL FINDINGS: We found novel isoforms of
      human DAT and NET produced by alternative splicing in human blood cells (DAT) and
      placenta (NET), both of which lacked the region encoded by exon 6. RT-PCR
      analyses showed a difference in expression between the full length (FL) and
      truncated isoforms in the brain and peripheral tissues, suggesting tissue
      specific alternative splicing. Heterologous expression of the FL but not
      truncated isoforms of DAT and NET in COS-7 cells revealed transport activity.
      However, immunocytochemistry with confocal microscopy and a cell surface
      biotinylation assay demonstrated that the truncated as well as FL isoform was
      expressed at least in part in the plasma membrane at the cell surface, although
      the truncated DAT was distributed to the cell surface slower than FL DAT. A
      specific antibody to the C-terminus of DAT labeled the variant but not FL DAT,
      when cells were not treated with Triton for permeabilization, suggesting the C
      terminus of the variant to be located extracellulary. Co-expression of the FL
      isoform with the truncated isoform in COS-7 cells resulted in a reduced uptake of
      substrates, indicating a dominant negative effect of the variant. Furthermore, an
      immunoprecipitation assay revealed physical interaction between the FL and
      truncated isoforms. CONCLUSIONS/SIGNIFICANCE: The unique expression and function
      and the proposed membrane topology of the variants suggest the importance of
      isoforms of catecholamine transporters in monoaminergic signaling in the brain
      and peripheral tissues.

PMID- 20700533
TI  - Adiponectin deficiency promotes tumor growth in mice by reducing macrophage
      infiltration.
AB  - Adiponectin is an adipocyte-derived plasma protein that has been implicated in
      regulating angiogenesis, but the role of adiponectin in regulating this process
      is still controversial. In this study, in order to determine whether adiponectin
      affects tumor growth and tumor induced vascularization, we implanted B16F10
      melanoma and Lewis Lung Carcinoma cells subcutaneously into adiponectin knockout
      and wild-type control mice, and found that adiponectin deficiency markedly
      promoted the growth of both tumors. Immunohistochemical analyses indicated that
      adiponectin deficiency reduced macrophage recruitment to the tumor, but did not
      affect cancer cell mitosis, apoptosis, or tumor-associated angiogenesis. In
      addition, treatment with recombinant adiponectin did not affect the proliferation
      of cultured B16F10 tumor cells. Importantly, the restoration of microphage
      infiltration at an early stage of tumorigenesis by means of co-injection of
      B16F10 cells and macrophages reversed the increased tumor growth in adiponectin
      knockout mice. Thus, we conclude that the enhanced tumor growth observed in
      adiponectin deficient mice is likely due to the reduction of macrophage
      infiltration rather than enhanced angiogenesis.

PMID- 20700534
TI  - Superpose3D: a local structural comparison program that allows for user-defined
      structure representations.
AB  - Local structural comparison methods can be used to find structural similarities
      involving functional protein patches such as enzyme active sites and ligand
      binding sites. The outcome of such analyses is critically dependent on the
      representation used to describe the structure. Indeed different categories of
      functional sites may require the comparison program to focus on different
      characteristics of the protein residues. We have therefore developed superpose3D,
      a novel structural comparison software that lets users specify, with a powerful
      and flexible syntax, the structure description most suited to the requirements of
      their analysis. Input proteins are processed according to the user's directives
      and the program identifies sets of residues (or groups of atoms) that have a
      similar 3D position in the two structures. The advantages of using such a general
      purpose program are demonstrated with several examples. These test cases show
      that no single representation is appropriate for every analysis, hence the
      usefulness of having a flexible program that can be tailored to different needs.
      Moreover we also discuss how to interpret the results of a database screening
      where a known structural motif is searched against a large ensemble of
      structures. The software is written in C++ and is released under the open source
      GPL license. Superpose3D does not require any external library, runs on Linux,
      Mac OSX, Windows and is available at http://cbm.bio.uniroma2.it/superpose3D.

PMID- 20700535
TI  - The native Wolbachia endosymbionts of Drosophila melanogaster and Culex
      quinquefasciatus increase host resistance to West Nile virus infection.
AB  - BACKGROUND: The bacterial endosymbiont Wolbachia pipientis has been shown to
      increase host resistance to viral infection in native Drosophila hosts and in the
      normally Wolbachia-free heterologous host Aedes aegypti when infected by
      Wolbachia from Drosophila melanogaster or Aedes albopictus. Wolbachia infection
      has not yet been demonstrated to increase viral resistance in a native Wolbachia
      mosquito host system. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we
      investigated Wolbachia-induced resistance to West Nile virus (WNV; Flaviviridae)
      by measuring infection susceptibility in Wolbachia-infected and Wolbachia-free D.
      melanogaster and Culex quinquefasciatus, a natural mosquito vector of WNV.
      Wolbachia infection of D. melanogaster induces strong resistance to WNV
      infection. Wolbachia-infected flies had a 500-fold higher ID50 for WNV and
      produced 100,000-fold lower virus titers compared to flies lacking Wolbachia. The
      resistance phenotype was transmitted as a maternal, cytoplasmic factor and was
      fully reverted in flies cured of Wolbachia. Wolbachia infection had much less
      effect on the susceptibility of D. melanogaster to Chikungunya (Togaviridae) and
      La Crosse (Bunyaviridae) viruses. Wolbachia also induces resistance to WNV
      infection in Cx. quinquefasciatus. While Wolbachia had no effect on the overall
      rate of peroral infection by WNV, Wolbachia-infected mosquitoes produced lower
      virus titers and had 2 to 3-fold lower rates of virus transmission compared to
      mosquitoes lacking Wolbachia. CONCLUSIONS/SIGNIFICANCE: This is the first
      demonstration that Wolbachia can increase resistance to arbovirus infection
      resulting in decreased virus transmission in a native Wolbachia-mosquito system.
      The results suggest that Wolbachia reduces vector competence in Cx.
      quinquefasciatus, and potentially in other Wolbachia-infected mosquito vectors.

PMID- 20700537
TI  - Gene expression in chicken reveals correlation with structural genomic features
      and conserved patterns of transcription in the terrestrial vertebrates.
AB  - BACKGROUND: The chicken is an important agricultural and avian-model species. A
      survey of gene expression in a range of different tissues will provide a
      benchmark for understanding expression levels under normal physiological
      conditions in birds. With expression data for birds being very scant, this
      benchmark is of particular interest for comparative expression analysis among
      various terrestrial vertebrates. METHODOLOGY/PRINCIPAL FINDINGS: We carried out a
      gene expression survey in eight major chicken tissues using whole genome
      microarrays. A global picture of gene expression is presented for the eight
      tissues, and tissue specific as well as common gene expression were identified. A
      Gene Ontology (GO) term enrichment analysis showed that tissue-specific genes are
      enriched with GO terms reflecting the physiological functions of the specific
      tissue, and housekeeping genes are enriched with GO terms related to essential
      biological functions. Comparisons of structural genomic features between tissue
      specific genes and housekeeping genes show that housekeeping genes are more
      compact. Specifically, coding sequence and particularly introns are shorter than
      genes that display more variation in expression between tissues, and in addition
      intergenic space was also shorter. Meanwhile, housekeeping genes are more likely
      to co-localize with other abundantly or highly expressed genes on the same
      chromosomal regions. Furthermore, comparisons of gene expression in a panel of
      five common tissues between birds, mammals and amphibians showed that the
      expression patterns across tissues are highly similar for orthologous genes
      compared to random gene pairs within each pair-wise comparison, indicating a high
      degree of functional conservation in gene expression among terrestrial
      vertebrates. CONCLUSIONS: The housekeeping genes identified in this study have
      shorter gene length, shorter coding sequence length, shorter introns, and shorter
      intergenic regions, there seems to be selection pressure on economy in genes with
      a wide tissue distribution, i.e. these genes are more compact. A comparative
      analysis showed that the expression patterns of orthologous genes are conserved
      in the terrestrial vertebrates during evolution.

PMID- 20700536
TI  - Oxytocin signaling in mouse taste buds.
AB  - BACKGROUND: The neuropeptide, oxytocin (OXT), acts on brain circuits to inhibit
      food intake. Mutant mice lacking OXT (OXT knockout) overconsume salty and sweet
      (i.e. sucrose, saccharin) solutions. We asked if OXT might also act on taste buds
      via its receptor, OXTR. METHODOLOGY/PRINCIPAL FINDINGS: Using RT-PCR, we detected
      the expression of OXTR in taste buds throughout the oral cavity, but not in
      adjacent non-taste lingual epithelium. By immunostaining tissues from OXTR-YFP
      knock-in mice, we found that OXTR is expressed in a subset of Glial-like (Type I)
      taste cells, and also in cells on the periphery of taste buds. Single-cell RT-PCR
      confirmed this cell-type assignment. Using Ca2+ imaging, we observed that
      physiologically appropriate concentrations of OXT evoked [Ca2+]i mobilization in
      a subset of taste cells (EC50 approximately 33 nM). OXT-evoked responses were
      significantly inhibited by the OXTR antagonist, L-371,257. Isolated OXT
      responsive taste cells were neither Receptor (Type II) nor Presynaptic (Type III)
      cells, consistent with our immunofluorescence observations. We also investigated
      the source of OXT peptide that may act on taste cells. Both RT-PCR and
      immunostaining suggest that the OXT peptide is not produced in taste buds or in
      their associated nerves. Finally, we also examined the morphology of taste buds
      from mice that lack OXTR. Taste buds and their constituent cell types appeared
      very similar in mice with two, one or no copies of the OXTR gene.
      CONCLUSIONS/SIGNIFICANCE: We conclude that OXT elicits Ca2+ signals via OXTR in
      murine taste buds. OXT-responsive cells are most likely a subset of Glial-like
      (Type I) taste cells. OXT itself is not produced locally in taste tissue and is
      likely delivered through the circulation. Loss of OXTR does not grossly alter the
      morphology of any of the cell types contained in taste buds. Instead, we
      speculate that OXT-responsive Glial-like (Type I) taste bud cells modulate taste
      signaling and afferent sensory output. Such modulation would complement central
      pathways of appetite regulation that employ circulating homeostatic and satiety
      signals.

PMID- 20700538
TI  - H-Ras nanocluster stability regulates the magnitude of MAPK signal output.
AB  - H-Ras is a binary switch that is activated by multiple co-factors and triggers
      several key cellular pathways one of which is MAPK. The specificity and magnitude
      of downstream activation is achieved by the spatio-temporal organization of the
      active H-Ras in the plasma membrane. Upon activation, the GTP bound H-Ras binds
      to Galectin-1 (Gal-1) and becomes transiently immobilized in short-lived
      nanoclusters on the plasma membrane from which the signal is propagated to Raf.
      In the current study we show that stabilizing the H-Ras-Gal-1 interaction, using
      bimolecular fluorescence complementation (BiFC), leads to prolonged
      immobilization of H-Ras.GTP in the plasma membrane which was measured by
      fluorescence recovery after photobleaching (FRAP), and increased signal out-put
      to the MAPK module. EM measurements of Raf recruitment to the H-Ras.GTP
      nanoclusters demonstrated that the enhanced signaling observed in the BiFC
      stabilized H-Ras.GTP nanocluster was attributed to increased H-Ras immobilization
      rather than to an increase in Raf recruitment. Taken together these data
      demonstrate that the magnitude of the signal output from a GTP-bound H-Ras
      nanocluster is proportional to its stability.

PMID- 20700539
TI  - FAD mutations in amyloid precursor protein do not directly perturb intracellular
      calcium homeostasis.
AB  - Disturbances in intracellular calcium homeostasis are likely prominent and
      causative factors leading to neuronal cell death in Alzheimer's disease (AD).
      Familial AD (FAD) is early-onset and exhibits autosomal dominant inheritance. FAD
      linked mutations have been found in the genes encoding the presenilins and
      amyloid precursor protein (APP). Several studies have shown that mutated
      presenilin proteins can directly affect calcium release from intracellular stores
      independently of Abeta production. Although less well established, there is also
      evidence that APP may directly modulate intracellular calcium homeostasis. Here,
      we directly examined whether overexpression of FAD-linked APP mutants alters
      intracellular calcium dynamics. In contrast to previous studies, we found that
      overexpression of mutant APP has no effects on basal cytosolic calcium, ER
      calcium store size or agonist-induced calcium release and subsequent entry. Thus,
      we conclude that mutated APP associated with FAD has no direct effect on
      intracellular calcium homeostasis independently of Abeta production.

PMID- 20700540
TI  - sRNAscanner: a computational tool for intergenic small RNA detection in bacterial
      genomes.
AB  - BACKGROUND: Bacterial non-coding small RNAs (sRNAs) have attracted considerable
      attention due to their ubiquitous nature and contribution to numerous cellular
      processes including survival, adaptation and pathogenesis. Existing computational
      approaches for identifying bacterial sRNAs demonstrate varying levels of success
      and there remains considerable room for improvement. METHODOLOGY/PRINCIPAL
      FINDINGS: Here we have proposed a transcriptional signal-based computational
      method to identify intergenic sRNA transcriptional units (TUs) in completely
      sequenced bacterial genomes. Our sRNAscanner tool uses position weight matrices
      derived from experimentally defined E. coli K-12 MG1655 sRNA promoter and rho
      independent terminator signals to identify intergenic sRNA TUs through sliding
      window based genome scans. Analysis of genomes representative of twelve species
      suggested that sRNAscanner demonstrated equivalent sensitivity to sRNAPredict2,
      the best performing bioinformatics tool available presently. However, each
      algorithm yielded substantial numbers of known and uncharacterized hits that were
      unique to one or the other tool only. sRNAscanner identified 118 novel putative
      intergenic sRNA genes in Salmonella enterica Typhimurium LT2, none of which were
      flagged by sRNAPredict2. Candidate sRNA locations were compared with available
      deep sequencing libraries derived from Hfq-co-immunoprecipitated RNA purified
      from a second Typhimurium strain (Sittka et al. (2008) PLoS Genetics 4:
      e1000163). Sixteen potential novel sRNAs computationally predicted and detected
      in deep sequencing libraries were selected for experimental validation by
      Northern analysis using total RNA isolated from bacteria grown under eleven
      different growth conditions. RNA bands of expected sizes were detected in
      Northern blots for six of the examined candidates. Furthermore, the 5'-ends of
      these six Northern-supported sRNA candidates were successfully mapped using 5'
      RACE analysis. CONCLUSIONS/SIGNIFICANCE: We have developed, computationally
      examined and experimentally validated the sRNAscanner algorithm. Data derived
      from this study has successfully identified six novel S. Typhimurium sRNA genes.
      In addition, the computational specificity analysis we have undertaken suggests
      that approximately 40% of sRNAscanner hits with high cumulative sum of scores
      represent genuine, undiscovered sRNA genes. Collectively, these data strongly
      support the utility of sRNAscanner and offer a glimpse of its potential to reveal
      large numbers of sRNA genes that have to date defied identification. sRNAscanner
      is available from: http://bicmku.in:8081/sRNAscanner or
      http://cluster.physics.iisc.ernet.in/sRNAscanner/.

PMID- 20700541
TI  - Candida albicans AGE3, the ortholog of the S. cerevisiae ARF-GAP-encoding gene
      GCS1, is required for hyphal growth and drug resistance.
AB  - BACKGROUND: Hyphal growth and multidrug resistance of C. albicans are important
      features for virulence and antifungal therapy of this pathogenic fungus.
      METHODOLOGY/PRINCIPAL FINDINGS: Here we show by phenotypic complementation
      analysis that the C. albicans gene AGE3 is the functional ortholog of the yeast
      ARF-GAP-encoding gene GCS1. The finding that the gene is required for efficient
      endocytosis points to an important functional role of Age3p in endosomal
      compartments. Most C. albicans age3Delta mutant cells which grew as cell clusters
      under yeast growth conditions showed defects in filamentation under different
      hyphal growth conditions and were almost completely disabled for invasive
      filamentous growth. Under hyphal growth conditions only a fraction of age3Delta
      cells shows a wild-type-like polarization pattern of the actin cytoskeleton and
      lipid rafts. Moreover, age3Delta cells were highly susceptible to several
      unrelated toxic compounds including antifungal azole drugs. Irrespective of the
      AGE3 genotype, C-terminal fusions of GFP to the drug efflux pumps Cdr1p and Mdr1p
      were predominantly localized in the plasma membrane. Moreover, the plasma
      membranes of wild-type and age3Delta mutant cells contained similar amounts of
      Cdr1p, Cdr2p and Mdr1p. CONCLUSIONS/SIGNIFICANCE: The results indicate that the
      defect in sustaining filament elongation is probably caused by the failure of
      age3Delta cells to polarize the actin cytoskeleton and possibly of inefficient
      endocytosis. The high susceptibility of age3Delta cells to azoles is not caused
      by inefficient transport of efflux pumps to the cell membrane. A possible role of
      a vacuolar defect of age3Delta cells in drug susceptibility is proposed and
      discussed. In conclusion, our study shows that the ARF-GAP Age3p is required for
      hyphal growth which is an important virulence factor of C. albicans and essential
      for detoxification of azole drugs which are routinely used for antifungal
      therapy. Thus, it represents a promising antifungal drug target.

PMID- 20700550
TI  - Physical conditioning programs for improving work outcomes among workers with
      back pain.
AB  - OBJECTIVES: The aim of this review was to assess the effect of physical
      conditioning programs, compared to no or alternative interventions, in reducing
      time lost from work among patients with back pain. METHODS: We conducted a
      systematic review with meta-analysis and meta-regression of randomized controlled
      trials (RCT) of physical conditioning programs for workers with back-pain-related
      work disability. RESULTS: We included 23 RCT with 3676 participants, with 13
      studies having a low risk of bias. In 14 studies, physical conditioning programs
      were compared to "usual care". Among workers with acute back pain, there was no
      effect on sickness absence. For workers with subacute back pain, we found
      conflicting results. Among workers with chronic back pain, pooled results of five
      studies showed a small effect on sickness absence at one year follow-up
      [standardized mean difference (SMD) -0.18, 95% confidence interval (95% CI) -0.37
      0.00] but this effect disappeared at longer follow-up times. Six studies compared
      physical conditioning programs to exercise only with conflicting results. The
      addition of cognitive behavioral therapy to physical conditioning programs did
      not change the effectiveness. The meta-regression showed no significant effect of
      program intensity, inclusion of a workplace visit, occupation, setting of the
      intervention, the type of comparison, or the follow up time. CONCLUSIONS: The
      effectiveness of physical conditioning programs in reducing sick leave for
      workers with back pain remains uncertain. For acute back pain, these programs
      probably have no effect; for subacute back pain, the effect is unclear, and for
      chronic back pain there is a small effect at one year follow-up that does not
      last in the long run. Remaining heterogeneity could not be explained by meta
      regression. A better understanding of the mechanism behind physical conditioning
      programs and return to work is needed to develop more effective interventions.

PMID- 20700542
TI  - Paradoxical effect of pertussis toxin on the delayed hypersensitivity response to
      autoantigens in mice.
AB  - BACKGROUND: Pertussis toxin (PTX), an exotoxin of Bordetella pertussis, enhances
      the development of experimental autoimmune diseases such as experimental
      autoimmune uveitis (EAU) and experimental autoimmune encephalomyelitis (EAE) in
      rodent models. The mechanisms of the promotion of experimental autoimmune
      diseases by PTX may be based upon PTX-induced disruption of the blood eye/brain
      barriers facilitating the infiltration of inflammatory cells, the modulation of
      inflammatory cell migration and the enhancement of the activation of inflammatory
      cells. We hypothesized that the facilitation of experimental autoimmunity by PTX
      suggests that its influence on the in vivo immune response to auto-antigen may
      differ from its influence on non-self antigens. METHODOLOGY/PRINCIPAL FINDINGS:
      We have evaluated the effect of PTX on the simultaneous generation of delayed
      type hypersensitivity (DTH) responses and autoimmune responses to uveitogenic
      interphotoreceptor retinoid binding protein peptide (IRBP161-180),
      encephalitogenic myelin oligodendrocyte glycoprotein peptide (MOG35-55) or
      ovalbumin (OVA). PTX injection of mice immunized to IRBP peptide161-180 led to
      (i) the development of EAU as shown by histopathology of the retina, (ii) pro
      inflammatory cytokine production by splenocytes in response to IRBP peptide161
      180, and (iii) symptomatic EAE in mice immunized with encephalitogenic MOG
      peptide35-55. However, mice that received PTX had a reduced DTH response to
      IRBP161-180 peptide or MOG peptide35-55 when challenged distal to the site
      affected by autoreactive T cells. Moreover, footpad challenge with MOG35-55
      peptide reduced EAE in mice immunized with MOG peptide. In contrast, the use of
      PTX when immunizing with OVA protein or an OVA immunogenic peptide did not affect
      the DTH response to OVA. CONCLUSIONS/SIGNIFICANCE: The results suggest that that
      the reduced DTH response in mice receiving PTX may be specific for autoantigens
      and autoantigen-reactive T cells are diverted away from ectopic sites that
      received the autoantigen and towards the tissue site of the autoantigen.

PMID- 20700551
TI  - Systemic retinoids: chemoprevention of skin cancer in transplant recipients.
AB  - Solid organ transplant recipients (OTRs) have an increased incidence of skin
      cancer, resulting in significant morbidity and mortality post-transplantation.
      Chemoprevention strategies are focused on reducing and delaying the development
      of skin cancer in these patients. Although systemic retinoids are widely used in
      OTRs, few randomized controlled trials have been performed. Limited data suggest
      that acitretin may have a beneficial role in high-risk OTRs. Since rebound flares
      occur upon discontinuation of retinoids, chemoprevention should be viewed as a
      lifelong therapy. Further studies are required to establish the efficacy and long
      term safety of systemic retinoids as chemopreventive agents for high-risk
      transplant recipients.

PMID- 20700552
TI  - Chemotherapy-induced hair loss.
AB  - Chemotherapy-induced hair loss occurs with an estimated incidence of 65%. Forty
      seven percent of female patients consider hair loss to be the most traumatic
      aspect of chemotherapy and 8% would decline chemotherapy due to fears of hair
      loss. At present, no approved pharmacologic intervention exists to circumvent
      this side-effect of anticancer treatment, though a number of agents have been
      investigated on the basis of the current understanding of the underlying
      pathobiology. Among the agents that have been evaluated, topical minoxidil was
      able to reduce the severity or shorten the duration, but it did not prevent hair
      loss. The major approach to minimize chemotherapy-induced hair loss is by scalp
      cooling, though most published data on this technique are of poor quality.
      Fortunately, the condition is usually reversible, and appropriate hair and scalp
      care along with temporarily wearing a wig may represent the most effective coping
      strategy. However, some patients may show changes in color and/or texture of
      regrown hair, and in limited cases the reduction in density may persist.

PMID- 20700553
TI  - The impact of methicillin-resistant Staphylococcus aureus colonisation on
      paediatric cystic fibrosis patients' morbidity.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) plays a well
      recognised pathogenic role in cystic fibrosis (CF). AIMS: To evaluate the
      prevalence and incidence of colonisation by MRSA, clinical impact of MRSA
      colonisation (year after first MRSA isolation), risk factors and pattern of
      antimicrobial resistance. METHODS: Retrospective review of paediatric CF patients
      colonised with MRSA followed-up at the CF Unit of Hospital de Santa Maria 2003
      2007. RESULTS: Twelve of the 60 patients followed-up during this period were MRSA
      positive at some time (chronic colonisation in 3 patients). Mean age at
      acquisition was 9 years 10 months and mean time interval between CF diagnosis and
      MRSA acquisition 5 years 7 months. An important rise in MRSA colonisation
      prevalence and incidence was observed, with the highest rate seen in 2007
      (prevalence 14.3% and incidence 8.9%). Four patients had received anti
      staphylococcal prophylaxis with flucloxacillin. An increase in the total number
      of in-patient days was observed in four patients (two with chronic colonisation).
      Deterioration in lung function was seen in five patients (including the three
      patients with chronic colonisation). Only one patient had a decrease in body mass
      index percentile. Resistance to clindamycin and rifampin was the most frequently
      seen. CONCLUSIONS: This study revealed significant clinical deterioration in
      patients with chronic colonisation by MRSA, reinforcing the importance of
      effective and timely decolonisation strategies.

PMID- 20700554
TI  - The health-related quality of life of patients with chronic obstructive pulmonary
      disease and asthma evaluated by the SGRQ.
AB  - AIMS: To compare the effects of asthma and chronic obstructive pulmonary disease
      (COPD) on the quality of life of patients evaluated using the Saint George
      Respiratory Questionnaire (SGRQ) through correlating the variables, domains and
      total score. METHODS: A cross-sectional study from October 2008 to March 2009
      with 75 adult outpatients at the University Hospital of Salamanca, Spain.
      Patients provided their clinical and socio-demographical data after being
      informed of the study's aims and ethical aspects. The Spanish version of the SGRQ
      and the statistical packa ge Statistics SPSS version 17.0 were used for
      statistical analysis. RESULTS: 65.3% were male and 34.7% female with mean age
      60.4 years. 68% had a diagnosis of asthma and 30.7% COPD. Statistically
      significant differences (p<0.05) between diagnosis and the 'activity' domain were
      found. None were found between gender, smoking, ex-smoking or hypertension and
      the domains. The income levels were inversely related (p=0.038) with the total
      score. Statistically significant differences between age and the 'activity'
      (p<0.01) and 'impact' (p<0.05) domains and the SGRQ total score were found
      (p<0.01). The forced expiratory volume in one second (FEV1%pred) only correlated
      with the 'activity' domain (p<0.01) and with the total score (p<0.01).
      CONCLUSIONS: No variable correlated with all domains and the total score of the
      instrument. Some presented no statistically significant difference.

PMID- 20700555
TI  - [Tuberculosis treatment and management of some problems related to the
      medication].
AB  - Tuberculosis is a well-known illness for which there is treatment of recognized
      effectiveness. In Portugal, tuberculosis incidence has been diminishing although
      keeping values higher than the rest of the Western Europe. A new challenge is
      associated with resistance to drugs, admittedly related to treatment
      noncompliance or incorrect treatment choice. The purpose of this review to focus
      our attention on the importance of the first approach to the tuberculosis case.

PMID- 20700556
TI  - Pertussis in Portugal - time for a new strategy.
AB  - The introduction of routine vaccination against Bordetella pertussis led to a
      drastic decline in the number of reported cases of pertussis. Nevertheless, a
      gradual increase in pertussis notifications has been observed in the last years,
      and political vaccination changes have been conducted in some countries.
      Pertussis epidemiology is reviewed, taking into account mathematical models
      studies concerning new vaccinal strategies for pertussis prevention and new
      international recommendations. Regarding Portugal, the need for a "booster" in
      adolescence is emphasized, and other recommendations for pertussis control are
      suggested.

PMID- 20700557
TI  - [Ultrasound in chest disease].
AB  - In the past few years transthoracic ultrasound has been recognized as an
      important tool for chest physicians. At present, ultrasound devices are
      practical, portable, easy to use and reliable, which makes them suited for
      diagnostic investigations as well as for therapeutic procedures guidance. Basic
      ultrasound technical expertise is required to assess pleural effusions and
      perform ultrasound -guided thoracentesis. More complex procedures can be done
      with specific training and include assistance to chest drain insertion and
      identification with potential biopsy of thoracic lesions. The authors aim to
      review, in a practical approach, the technique and recent developments in this
      field. Clinical cases are presented in order to illustrate and guide the beginner
      in chest ultrasound.

PMID- 20700558
TI  - [Acute fibrinous and organizing pneumonia].
AB  - The histologic pattern of Acute Fibrinous and Organizing Pneumonia (AFOP),
      described by Beasley in 2002, is characterized by the existence of intra alveolar
      fibrin in the form of fibrin "balls" and diffuse organizing pneumonia. Presenting
      symptoms of this interstitial pulmonary disease can be acute or subacute.
      However, it differs from the well -recognized histologic patterns of acute
      pulmonary lesion - Diffuse Alveolar Damage (DAD), Organizing Pneumonia (OP) and
      Eosinophilic Pneumonia (EP). The authors carry out a review of the literature
      concerning this topic and describe the clinical case of a 44 -year -old patient
      with unusual imaging features and outcome.

PMID- 20700559
TI  - [Effects of asthma on nutritional status in children: a systematic review].
AB  - INTRODUCTION: Asthma is a chronic inflammatory disease of high prevalence,
      considered a public health problem and is thought to be one cause of low birth
      weight and growth retardation. PURPOSE: The purpose of this article was to review
      in literature the effects of asthma on the nutritional status in children.
      MATERIAL AND METHODS: A systematic review was made by searching for articles in
      PubMed, SciELO and LILACS databases. Review articles, studies with adults or
      research that did not evaluate the effects of asthma in children were excluded.
      Hence original articles in humans were included. RESULTS: In the systematic
      review we found 901 articles in MEDLINE (1966-1996), 47 in LILACS and SciELO in
      the 16 - Brazil, totaling 964 articles. Of these, 17 articles were selected.
      CONCLUSION: Evidence that asthma interferes in nutritional status can not be
      proven in this study.

PMID- 20700560
TI  - [Understanding the classification, physiopathology and the diagnostic radiology
      of bronchiectasis].
AB  - Bronchiectasis is defined as an abnormal persistent bronchial dilatation usually
      associated with inflammation in the bronchial tree and lung parenchyma. The
      disease remains a common cause of significant morbidity and mortality, especially
      when associated with hereditary disorders such as cystic fibrosis, ciliary
      dyskinesia, and immunodeficiency states. Computed tomography is now the
      diagnostic modality of choice and may also contribute to clinical management,
      suggesting some etiologic causes. We highlight developments in classification,
      physiopathology and radiology of this debilitating disease.

PMID- 20700561
TI  - [Influence of perception of chronic obstructive pulmonary disease in promotion of
      self-management of disease].
AB  - OBJECTIVE: Identify the state of the art about the influence of illness
      perceptions in the promotion of self -management in patients with COPD. METHOD:
      We conducted a systematic review of the literature, using the method of PICOS,
      the systematic literature review includes the years 2004 to 2009 and was
      conducted between August and September 2009. RESULTS: Four articles met the
      inclusion criteria, including a review of the literature and three qualitative
      studies. Clients with higher perception of disease control and greater self 
      efficacy, with stable emotional situations, have better results in self -control
      of the disease. The evaluation, discussion and clarification of beliefs,
      attitudes and their impact on self -confidence and self -control should be
      integrated into clinical practice. CONCLUSION: The perceived lack of control over
      the course of the disease contributes to reduced quality of life, creates
      anxiety, leads to social isolation, can lead to depression, and reduces the
      motivation to acquire knowledge and skills for self -control disease. The lack of
      motivation, the inability to recognize the cognitive, instrumental capabilities,
      social support and support of health professionals, power the low self -control
      of the disease and non -adherence to therapy.

PMID- 20700562
TI  - [Pulmonary obstructive chronic disease and physical exercise].
AB  - Chronic Obstructive Pulmonary Disease (COPD) is a disease that can be prevented
      and treated, with a pulmonary component and with significant systemic effects
      that contribute to the severity of clinical manifestations. COPD causes a number
      of changes, including those which lead to exercise tolerance limitation and to a
      progressive deterioration of life quality of the patients. Respiratory
      rehabilitation (RR) represents a key part of the treatment. The benefits of RR
      are independent of sex, age and disease severity. At the end of the program, the
      patient should have acquired a life style as independent and healthy as possible.
      With this article the authors intend to review the benefits of physical exercise
      in rehabilitation of patients with COPD and the different types of training used
      in the respiratory rehabilitation program established for each patient.

PMID- 20700563
TI  - Watermelon stomach, hemorrhagic pericarditis, small cell carcinoma of the lung
      and synchronous squamous cell carcinoma of the tongue base.
AB  - Based on a case of gastric antral vascular ectasia (watermelon stomach) that was
      associated with hemorrhagic pericarditis, small cell lung carcinoma with
      mediastinal lymph node metastases and a synchronous squamous cell carcinoma of
      the base of the tongue, the authors made a review of the clinical, endoscopic and
      histopathological aspects of this type of gastropathy, and its association with
      other diseases, and of the results of its endoscopic therapy. The causes of
      hemorrhagic pericarditis are considered, emphasizing the necessity to know if the
      effusion has a malignant etiology. To the best of our knowledge the association
      of watermelon stomach to small cell lung carcinoma and squamous cell carcinoma of
      the base of the tongue has not yet been described. Extensive metastases to
      mediastal lymph nodes are common to small cell lung carcinoma.

PMID- 20700564
TI  - [Pulmonary disease in polymyositis].
AB  - INTRODUCTION: Polymyositis and dermatomyositis are classified as idiopathic
      inflammatory myopathies. Interstitial lung disease is rare and is described in
      the literature in about 10% of cases. The authors describes a case of 75 year old
      woman presenting with one month evolution of fever, weight loss, arthralgia,
      myalgia and symmetric and proximal muscle weakness of upper and lower limbs.
      Nonspecific interstitial changes was found in chest X -ray. After exhaustive
      study, the diagnosis of pulmonary involvement in the form of organizing pneumonia
      by polymyositis, was established. Glucocorticoids and mycophenolate were
      prescribed with good clinical, analytical and radiological outcome. CONCLUSION:
      In this case, it was the changes in the chest X -ray in a patient without
      respiratory symptomatology, that conducted to exhaustive study to polymyositis
      diagnosis, enhancing once again the importance of X -ray in the screening of
      pathologies of other systems.

PMID- 20700565
TI  - [Hepatopulmonary syndrome: case report and literature review].
AB  - Hepatopulmonary syndrome is an important complication of chronic liver disease
      occurring in 16 24% of patients. It is characterized by an increase in alveolar 
      capillary gradient, with or without hypoxemia, due to intrapulmonary
      vasodilatation. The course of the disease is progressive and associated with
      increased morbidity and mortality. There is no effective medical treatment and
      liver transplant is a priority. To exemplify the authors present the case of a 39
      year -old male patient sent to the Pulmonology outpatient clinic and presenting
      with secondary polycythemia and progressive exertional dyspnoea. Clinical
      investigation identified a hepatopulmonary syndrome.

PMID- 20700566
TI  - [Shrinking lung syndrome: case report and literature review].
AB  - Respiratory complications of systemic lupus erythematosus may involve every
      element of the respiratory system and are relatively common as the initial
      manifestation of this disease occurring in 60 -80% of patients during the course
      of the disease. The authors report a case of a lupic patient with a respiratory
      manifestation rarely recognized which diagnostic approach and treatment still
      represents a clinical challenge.

PMID- 20700567
TI  - [Kidney in sepsis : Victim and accomplice].

PMID- 20700568
TI  - [Intrathoracic kidneys : review and case report].
AB  - Intrathoracic kidneys are rare and are often only diagnosed incidentally. The
      literature on intrathoracic kidneys in children and adults is reviewed and
      discussed, focusing on diagnostic procedures and surgical therapy. Additionally,
      the case of a 35-year-old woman with a relapse of a left-sided intrathoracic
      kidney after pregnancy is reported. Diagnostic procedures and the surgical
      management are discussed.

PMID- 20700569
TI  - [Pathophysiology and biochemistry of platelets].
AB  - Although their central role is to control bleeding and to induce thrombosis,
      platelets are important inflammatory and immune cells as well as modulators of
      angiogenesis. This review focuses on the different roles of platelets in
      hemostasis, thrombosis, inflammation, arteriosclerosis, angiogenesis,
      antimicrobial host defense and hematogenous tumor metastasis. Platelets are the
      central regulators of hemostasis. On their surface the important thrombin burst
      takes place. Platelets cause atherothrombotic vascular occlusions. However, they
      are probably involved in early stages of arteriosclerosis, e.g. extravasation of
      leukocytes at sites of vascular injury, formation of foam cells and proliferation
      of smooth muscle cells. These processes are triggered by secretion of
      proinflammatory substances and growth factors as well as by platelet-cell
      interactions via specific adhesive axes. During infections platelets kill
      pathogens through secretion of antimicrobial substances and extracellular traps
      or nets. Platelets facilitate the revascularisation of ischemic tissue and
      therefore even promote tumor growth.

PMID- 20700570
TI  - [Significance of platelet function tests].
AB  - Numerous laboratory tests are in use to detect congenital or acquired platelet
      function disorders. Platelet aggregometry, using ADP, collagen, arachidonic acid
      or ristocetin as inductor is the standard test system for diagnosis. It is also
      used to detect platelet non-response to antiplatelet therapy. Studies have
      demonstrated that laboratory assessment of platelet non response to aspirin or
      clopidogrel is associated with adverse outcomes, and they indicate the importance
      of adjusting antiplatelet therapy in patients with a low degree of platelet
      inhibition. Nevertheless, a standardized method for identifying these patients is
      still missing.

PMID- 20700571
TI  - [Trauma care systems in Germany, USA and Australia. An international comparison].
AB  - Due to the development of trauma care systems the treatment results of multiply
      injured patients have clearly improved during the last decades. More
      sophisticated preclinical algorithms, standardized procedures in the emergency
      room, calculated surgical strategies during the early phases and the subsequent
      intensive care (ICU) treatment as well as the implementation of trauma registries
      have all contributed to an improvement in trauma care. Different national trauma
      care systems have been developed due to the structural, geographic and
      demographic differences of the compared countries. However, large financial
      resources are required to maintain all three trauma care systems. To cope with
      financial losses in multiple trauma care, huge efforts of all the personnel
      involved are necessary to maintain the maximum treatment quality. In this
      context, national trauma registries, as well as the recently established trauma
      networks in Germany, might be helpful. Due to improvements in comprehensive
      trauma care and identification of expensive, but not prognosis improving
      treatment strategies, costs can be reduced by trauma registries and trauma
      networks.

PMID- 20700572
TI  - [Evaluation of an objective structured clinical examination (OSCE) in surgery and
      orthopedics by medical students].
AB  - BACKGROUND: The objective structured clinical exam (OSCE) has become an
      established form of examination. However, for general and orthopedic surgery it
      has barely been evaluated. Therefore, the present study was performed to analyze
      the OSCE in surgery by the students of the University of Ulm. MATERIAL AND
      METHODS: In total 304 medical students undertaking the OSCE were included in the
      study. The students were asked to fill out a standardized questionnaire which
      contained different evaluation parameters, such as test adequacy,
      comprehensibility, balance, difficulty, atmosphere and clinical relevance as well
      as self-assessment and overall rating. RESULTS: In the overall rating the OSCE
      was rated as having a clinical relevance. The preferred preparation strategies
      were the clinical traineeship and standard medical textbooks. Altogether, the
      OSCE was chosen as the preferred future examination method, followed by multiple
      choice testing and clinical practical examination. CONCLUSION: The evaluation of
      the OSCE by the medical students at the University of Ulm showed a high
      acceptance rate as well as a high clinical relevance.

PMID- 20700573
TI  - Complete loss of photoperiodic response in the rice mutant line X61 is caused by
      deficiency of phytochrome chromophore biosynthesis gene.
AB  - In rice (Oryza sativa), a short-day plant, photoperiod is the most favorable
      external signal for floral induction because of the constant seasonal change
      throughout the years. Compared with Arabidopsis, however, a large part of the
      regulation mechanism of the photoperiodic response in rice still remains unclear
      due mainly to the lack of induced mutant genes. An induced mutant line X61
      flowers 35 days earlier than its original variety Gimbozu under a natural
      photoperiod in Kyoto (35 degrees 01'N). We attempted to identify the mutant gene
      conferring early heading to X61. Experimental results showed that the early
      heading of X61 was conferred by a complete loss of photoperiodic response due to
      a novel single recessive mutant gene se13. This locus interacts with two crucial
      photoperiod sensitivity loci, Se1 and E1. Wild type alleles at these two loci do
      not function in coexistence with se13 in a homozygous state, suggesting that Se13
      is an upstream locus of the Se1 and E1 loci. Linkage analysis showed that Se13 is
      located in a 110 kb region between the two markers, INDEL3735_1 and INDEL3735_3
      on chromosome 1. A database search suggested that the Se13 gene is identical to
      AK101395 (=OsHY2), which encodes phytochromobilin synthase, a key enzyme in
      phytochrome chromophore biosynthesis. Subsequent sequence analysis revealed that
      X61 harbors a 1 bp insertion in exon 1 of OsHY2, which induces a frame-shift
      mutation producing a premature stop codon. It is therefore considered that the
      complete loss of photoperiodic response of X61 is caused by a loss of function of
      the Se13 (OsHY2) gene involved in phytochrome chromophore biosynthesis.

PMID- 20700574
TI  - Fine mapping of the sunflower resistance locus Pl(ARG) introduced from the wild
      species Helianthus argophyllus.
AB  - Downy mildew, caused by Plasmopara halstedii, is one of the most destructive
      diseases in cultivated sunflower (Helianthus annuus L.). The dominant resistance
      locus Pl(ARG) originates from silverleaf sunflower (H. argophyllus Torrey and
      Gray) and confers resistance to all known races of P. halstedii. We mapped
      Pl(ARG) on linkage group (LG) 1 of (cms)HA342 * ARG1575-2, a population
      consisting of 2,145 F(2) individuals. Further, we identified resistance gene
      candidates (RGCs) that cosegregated with Pl(ARG) as well as closely linked
      flanking markers. Markers from the target region were mapped with higher
      resolution in NDBLOS(sel) * KWS04, a population consisting of 2,780 F(2)
      individuals that does not segregate for Pl(ARG). A large-insert sunflower
      bacterial artificial chromosome (BAC) library was screened with overgo probes
      designed for markers RGC52 and RGC151, which cosegregated with Pl(ARG). Two RGC
      containing BAC contigs were anchored to the Pl(ARG) region on LG 1.

PMID- 20700575
TI  - Healthcare costs in patients with diabetes mellitus and comorbid mental disorders
      -a systematic review.
AB  - AIMS/HYPOTHESIS: We systematically reviewed the impact of comorbid mental
      disorders on healthcare costs in persons with diabetes. METHOD: We conducted a
      comprehensive search for studies investigating adult persons (>= 18 years old)
      with diabetes mellitus. All studies that allowed comparison of healthcare costs
      between diabetic patients with mental disorders and those without were included.
      RESULTS: We identified 4,273 potentially relevant articles from a comprehensive
      database search. Of these, 31 primary studies (39 publications) fulfilled
      inclusion criteria, of which 27 examined comorbid depression. Hospitalisation
      rates and hospitalisation costs, frequency and costs of outpatient visits,
      emergency department visits, medication costs and total healthcare costs were
      mainly increased with small to moderate effect sizes in patients with diabetes
      and comorbid mental disorders compared with diabetic patients without such
      problems. Frequency (standardised mean difference [SMD] =0.35-1.26) and costs
      (SMD =0.33-0.85) of mental health specialist visits were increased in the group
      with mental health comorbidity. Results regarding diabetes-related preventive
      services were inconsistent but point to a reduced utilisation rate in diabetic
      patients with comorbid mental disorders. Statistical heterogeneity between
      studies was high (I (2) range 64-98%). Pooled overall effects are therefore not
      reported. Studies included differ substantially regarding sample selection,
      assessment of diabetes and comorbid mental disorders, as well as in assessment of
      cost variables. CONCLUSIONS/INTERPRETATION: In light of the increased healthcare
      costs and inadequate use of preventive services, comorbid mental disorders in
      patients with diabetes must become a major focus of diabetes healthcare and
      research.

PMID- 20700576
TI  - Oral disease and subsequent cardiovascular disease in people with type 2
      diabetes: a prospective cohort study based on the Action in Diabetes and Vascular
      Disease: Preterax and Diamicron Modified-Release Controlled Evaluation (ADVANCE)
      trial.
AB  - AIMS/HYPOTHESIS: While there are plausible biological mechanisms linking oral
      health with cardiovascular disease (CVD) and mortality rates, no study, to our
      knowledge, has examined this association in a representative population of people
      with type 2 diabetes. METHODS: We used the Action in Diabetes and Vascular
      Disease: Preterax and Diamicron Modified-Release Controlled Evaluation (ADVANCE)
      study, a large, detailed, randomised controlled trial among a general population
      of individuals with type 2 diabetes. For the purposes of the present analyses,
      data from the trial are used within a prospective cohort study design. A total of
      10,958 men and women, aged 55 to 88 years and with type 2 diabetes, participated
      in a baseline medical examination, during which they counted their number of
      natural teeth and reported the number of days that their gums had bled over the
      preceding year. Study members were followed up for mortality and morbidity over 5
      years. RESULTS: After controlling for a range of potential confounding factors,
      the group with no teeth had a markedly increased risk of death due to all causes
      (HR 1.48, 95% CI 1.24-1.78), CVD (1.35, 1.05-1.74) and non-CVD (1.64, 1.26-2.13),
      relative to the group with the most teeth (>=22 teeth). Frequency of bleeding
      gums was not associated with any of the outcomes of interest. There was no
      suggestion that treatment group or sex modified these relationships.
      CONCLUSIONS/INTERPRETATION: In people with type 2 diabetes, oral disease, as
      indexed by fewer teeth, was related to an increased risk of death from all causes
      and of death due to CVD and non-CVD.

PMID- 20700577
TI  - Impact assessment of respirable suspended particulate matter from diesel
      generator sets used for pumping station.
AB  - Prediction of respirable suspended particulate matter impacts of diesel generator
      sets used for pumping station has been made using meteorological data,
      information on stack characteristics and emission rate, baseline ambient
      particulate matter and Industrial Source Complex Short Term (ISCST-3) model. It
      is observed that particulate matter emission from pumping station-S workplace
      diesel generator sets ranged from 2.4 to 436.5 mg Nm-3 and while at pumping
      station-C, it ranged from 23.2 to 186.5 mg Nm-3. The predicted and ambient
      respirable suspended particulate matter concentrations are below the national air
      quality standard for respirable suspended particulate matter in a mixed
      industrial area. Metals contents in respirable suspended particulate matter
      indicate the origin of crustal and mobile sources. Therefore, the impact of
      diesel generator sets used for pumping of crude oil on local air quality would be
      acceptable.

PMID- 20700578
TI  - Petroleum hydrocarbon concentrations in marine sediments along Chennai Coast, Bay
      of Bengal, India.
AB  - The spatial and temporal distribution of petroleum hydrocarbons (PHC) in marine
      sediments along the Chennai coast, Bay of Bengal was quantified by Ultra-Violet
      Fluorescence (UVF) Spectroscopy. The concentration of PHC in surface sediments
      varied from 1.88 to 39.76 ppm. The highest values obtained in the northern part
      of the study area, where shipping activities and land-based waste waters disposed
      into sea through the rivers like Kuvam and Adayar. The Adayar (7.26-16.83 ppm)
      and Kuvam (5.5-39.72 ppm) cores reveal a clear horizon of increase in PHC above
      50 and 35 cm respectively. PHC values showed a decreasing pattern with depth in
      all sediment cores suggesting the excess anthropogenic loading occurring in the
      recent past. The present study revealed that the PHC values of Chennai coastal
      sediments are lower than the values reported from selected costal areas including
      the sediment of the Mumbai coast (7.6-42.8 ppm), Arabian Sea. The results will be
      useful for pollution monitoring program along the coastal region and also to
      check the level of petroleum hydrocarbons in marine sediments.

PMID- 20700579
TI  - Anterior-superior internal impingement of the shoulder: an evidence-based review.
AB  - PURPOSE: Internal impingement syndrome is a painful shoulder condition related to
      the impingement of the soft tissue, including the rotator cuff, joint capsule and
      the long head of the biceps tendon and glenoid labrum. Two types of internal
      impingement syndrome can be differentiated: posterior-superior impingement and
      anterior-superior impingement (ASI). The aetiology of ASI in particular is not
      clear. The purpose of this paper is to discuss the different aetiological
      theories relating to ASI, try to clarify the clinical, radiological and
      arthroscopic findings and, finally, suggesting treatment for this complex
      shoulder syndrome. METHODS: The article is based on own research and clinical
      experience, as well as a non-systematic search in the PubMed database. RESULTS:
      The aetiology of ASI appears to be related to the pulley lesion and instability
      of the long head of the biceps tendon. It can be caused by trauma or degenerative
      factors, which produces anterior shoulder pain in middle-aged patients,
      particularly when performing overhead activities. CONCLUSION: The ASI is probably
      more frequent than previously reported. There is no evidence to prove the
      efficacy of a specific rehabilitative protocol, and the gold standard of surgical
      management has to be ascertained. However, in patients with a pulley lesion,
      there is some evidence that early surgical management, when minor soft injury
      lesions are present, produces better clinical outcomes.

PMID- 20700580
TI  - Development and validation of a disease model for postmenopausal osteoporosis.
AB  - This article describes the development of a model for postmenopausal osteoporosis
      (PMO) based on Swedish data that is easily adaptable to other countries.
      INTRODUCTION: The aims of the study were to develop and validate a model to
      describe the current/future burden of PMO in different national settings.
      METHODS: For validation purposes, the model was developed using Swedish data and
      provides estimates from 1990. For each year of the study, the "incident cohort"
      (women experiencing a first osteoporotic fracture) was identified and run through
      a Markov model using 1-year cycles until 2020. Health states were based on the
      number of fractures and death. Fracture by site (hip, vertebral, and non-hip non
      vertebral) was tracked for each health state. Transition probabilities reflected
      site-specific risk of death and subsequent fractures. Bone mineral density (BMD)
      was included as a model output; model inputs included population size and life
      tables from 1970 to 2020, incidence of fracture, relative risk of subsequent
      fractures based on prior fracture, relative risk of death following a fracture by
      site, and BMD by age (mean and standard deviation). RESULTS: Model predictions
      averaged across age groups estimated the incidence of hip, vertebral, and other
      osteoporotic fractures within a 5% margin of error versus published data. In
      Sweden, the number of osteoporotic fractures is expected to rise by 11.5% between
      2009 and 2020, with a shift towards more vertebral fractures and multiple
      fractures. CONCLUSION: The current PMO disease model is easily adaptable to other
      countries, providing a consistent measure of present and future burden of PMO in
      different settings.

PMID- 20700581
TI  - The effect of weight and weight change on the long-term precision of spine and
      hip DXA measurements.
AB  - SUMMARY: We examined the effect of weight and weight change on the long-term
      precision of spine and hip bone mineral density (BMD) in a group of 64
      postmenopausal women studied over a 10-year period. Long-term precision errors
      were 50% larger than short-term errors. Over the range 50-90-kg weight was
      associated with a statistically significantly larger precision error when
      precision was expressed in BMD units, but not when expressed as the coefficient
      of variation (CV). Weight changes up to 5 kg had little effect on precision.
      INTRODUCTION: Reliable knowledge of the precision of bone mineral density (BMD)
      measurements is important for the interpretation of follow-up dual-energy X-ray
      absorptiometry (DXA) scans. In this study, we examined the effect of body weight
      and change in weight on the long-term precision of spine and hip BMD. METHODS:
      The study population was a group of 64 postmenopausal women enrolled in a 16-year
      trial of tibolone. We analyzed the spine, femoral neck, and total hip BMD data
      acquired over a 10-year period on a Hologic QDR4500A densitometer using linear
      regression to examine the trend of BMD with time for each subject. Precision was
      expressed in BMD units (g cm(-2)) (standard error of the estimate, SEE) and also
      as the coefficient of variation (CV). RESULTS: The long-term precision errors
      were in BMD (CV) units: 0.018 g cm(-2) (1.9%) for spine, 0.017 g cm(-2) (2.3%)
      for femoral neck, and 0.016 g cm(-2) (1.7%) for total hip BMD. An inverse
      relationship between CV and BMD was found for the spine (P = 0.003) and total hip
      (P = 0.043) sites, but none between SEE and BMD. For spine BMD, there were
      statistically significant correlations between SEE and weight (P = 0.025) and
      body thickness (P = 0.027). For femoral neck BMD, there were correlations between
      SEE and weight (P = 0.030), body mass index (BMI) (P = 0.023) and thickness (P =
      0.021), but no correlations for total hip BMD or when precision was expressed as
      the CV. When study subjects were grouped in quartiles according to weight, the
      spine BMD SEE increased from 0.014 g cm(-2) for women in the lowest quartile (46
      62 kg) to 0.018 g cm(-2) for women in the highest quartile (80-105 kg) (P =
      0.008). There was a trend for SEE to be greater in individuals with larger weight
      changes, although these tended to be the heavier subjects. CONCLUSIONS: From the
      study, we were able to come up with the following conclusions: (1) long-term
      precision errors were 50% larger than short-term errors, (2) over the range 50 to
      90 kg (BMI: 20-35 kg m(-2)), body weight had a small but statistically
      significant effect on precision expressed in BMD units, but not when expressed as
      the CV, and (3) weight changes up to 5 kg had little effect on precision. More
      studies of individuals >100 kg are required to fully investigate the dependence
      of DXA scan precision on weight.

PMID- 20700582
TI  - Effect of osmotic stress on plant growth promoting Pseudomonas spp.
AB  - In this study we isolated and screened drought tolerant Pseudomonas isolates from
      arid and semi arid crop production systems of India. Five isolates could tolerate
      osmotic stress up to -0.73 MPa and possessed multiple PGP properties such as P
      solubilization, production of phytohormones (IAA, GA and cytokinin),
      siderophores, ammonia and HCN however under osmotic stress expression of PGP
      traits was low compared to non-stressed conditions. The strains were identified
      as Pseudomonas entomophila, Pseudomonas stutzeri, Pseudomonas putida, Pseudomonas
      syringae and Pseudomonas monteilli respectively on the basis of 16S rRNA gene
      sequence analysis. Osmotic stress affected growth pattern of all the isolates as
      indicated by increased mean generation time. An increase level of intracellular
      free amino acids, proline, total soluble sugars and exopolysaccharides was
      observed under osmotic stress suggesting bacterial response to applied stress.
      Further, strains GAP-P45 and GRFHYTP52 showing higher levels of EPS and osmolytes
      (amino acids and proline) accumulation under stress as compared to non-stress
      conditions, also exhibited higher expression of PGP traits under stress
      indicating a relationship between stress response and expression of PGP traits.
      We conclude that isolation and screening of indigenous, stress adaptable strains
      possessing PGP traits can be a method for selection of efficient stress tolerant
      PGPR strains.

PMID- 20700583
TI  - Development and validation of a sandwich ELISA for the determination of
      potentially allergenic sesame (Sesamum indicum) in food.
AB  - This paper presents a sandwich enzyme-linked immunosorbent assay (ELISA) that
      allows the determination of traces of sesame in food. Chicken anti-sesame
      antibodies, used as coating antibodies, and rabbit anti-sesame antibodies, used
      as secondary antibodies, were prepared by immunization with a protein extract of
      white, peeled sesame. The ELISA did not show any cross-reactivity with 19 food
      ingredients commonly found in sesame-containing foodstuffs such as seeds, nuts,
      and cereals. In whole grain bread, crisp toast, and snacks, the limit of
      detection (S/N = 3) was 0.5, 0.5, and 0.3 MUg sesame protein/g, and the limit of
      quantification (S/N = 10) was 0.6, 0.8, and 1.4 MUg sesame protein/g,
      respectively. The analysis of blank food matrices (whole grain bread, white
      bread, crisp toast, and snacks) spiked with sesame protein at four spike levels
      generally resulted in mean recoveries from 72% to 145%. In the case of spiking
      blank food matrices with sesame seeds, the ELISA proved to be more accurate for
      whole wheat cookies than for whole wheat bread.

PMID- 20700584
TI  - Limited effects of frequent CYP2D6*36-*10 tandem duplication allele on in vivo
      dextromethorphan metabolism in a Japanese population.
AB  - PURPOSE: although CYP2D6*36 was thought to be one of the alleles causing the poor
      metabolizer phenotype, several in vitro studies clarified that the enzyme
      produced by CYP2D6*36 showed enzymatic activities. However, the effects of
      CYP2D6*36 in tandem with CYP2D6*10 on the in vivo CYP2D6 activity have been
      unclear. In this study, we investigated in vivo metabolic capacities of CYP2D6
      among the subjects carrying different numbers of CYP2D6*36 in tandem with
      CYP2D6*10. METHODS: we measured the metabolic ratio (MR) of dextromethorphan in
      98 subjects. We determined the CYP2D6 genotype of these subjects, including
      allelic copy number of CYP2D6*10 and CYP2D6*36 by direct sequencing, TaqMan
      assay, and real-time Invader assay. RESULTS: single copies of CYP2D6*10 and
      tandem duplication of CYP2D6*36-*10 alleles were found at frequencies of 8.7 and
      32.7%, respectively. Median dextromethorphan MRs of the subjects carrying
      CYP2D6*10 and CYP2D6*36-*10 were not significantly different (P = 0.24).
      CONCLUSIONS: CYP2D6*36 in tandem with CYP2D6*10 plays a minor role in
      interindividual variation of dextromethorphan metabolism in vivo.

PMID- 20700585
TI  - Lipidbook: a public repository for force-field parameters used in membrane
      simulations.
AB  - Lipidbook is a public database for force-field parameters with a special emphasis
      on lipids, detergents and similar molecules that are of interest when simulating
      biological membrane systems. It stores parameter files that are supplied by the
      community. Topologies, parameters and lipid or whole bilayer structures can be
      deposited in any format for any simulation code, preferably under a license that
      promotes "open knowledge." A number of mechanisms are implemented to aid a user
      in judging the appropriateness of a given parameter set for a project. For
      instance, parameter sets are versioned, linked to the primary citation via PubMed
      identifier and digital object identifier (DOI), and users can publicly comment on
      deposited parameters. Licensing and, hence, the conditions for use and
      dissemination of academically generated data are often unclear. In those cases it
      is also possible to provide a link instead of uploading a file. A snapshot of the
      linked file is then archived using the WebCite((r)) service without further
      involvement of the user or Lipidbook, thus ensuring a transparent and permanent
      history of the parameter set. Lipidbook can be accessed freely online at
      http://lipidbook.bioch.ox.ac.uk. Deposition of data requires online registration.

PMID- 20700586
TI  - Efficacy and outcome of percutaneous nephrolithotomy in patients with calculus
      nephropathy.
AB  - The aim of this study was to prospectively evaluate the efficacy and outcome of
      percutaneous nephrolithotomy in patients with nephrolithiasis and chronic renal
      insufficiency. Between January 2006 and June 2009, 30 patients (20 males and 10
      females; mean age 45 years, range 18-65; mean serum creatinine 6.3 +/- 1.57 mg%)
      with calculus nephropathy were treated in our department. In 25 patients with
      obstructed and infected systems preliminary percutaneous nephrostomy or double J
      stenting was done. After stabilization and treatment of sepsis, percutaneous
      nephrolithotomy was done. Eight patients underwent bilateral procedure and 22
      underwent unilateral procedure. Twenty-two patients needed a single sitting while
      eight patients needed two sittings for stone clearance. The renal function was
      monitored by serial creatinine estimations. Of the 30 patients, 27 patients
      achieved complete clearance. Renal function was improved in 27 patients. Six
      patients developed postoperative sepsis. Two patients required angioembolization
      for uncontrollable bleeding. There was no mortality. Patients with calculus
      nephropathy can be salvaged using PNL with good improvement in renal function and
      acceptable morbidity when appropriate preoperative preparation and perioperative
      care are given.

PMID- 20700587
TI  - Thoracoabdominal situs: a practical approach accompanied by a short history of
      descriptive terms.
AB  - Classification systems for thoracoabdominal situs have been the subject of
      numerous reports, yet confusion persists. This essay presents an abbreviated
      historical review of the currently used terms, briefly discusses some of the
      nomenclature controversies, and proposes a classification system that more
      closely adheres to the etymology of the descriptors, especially "heterotaxy."

PMID- 20700588
TI  - Assessment of ventricular function and dyssynchrony before and after stage 2
      palliation of hypoplastic left heart syndrome using two-dimensional speckle
      tracking.
AB  - Two-dimensional (2D) speckle tracking (2DST) is a new technique independent of
      ventricular geometry but not independent of preload and afterload. Using 2DST,
      this study aimed to investigate differences in right ventricular (RV) function
      and intraventricular dyssynchrony in patients with hypoplastic left heart
      syndrome (HLHS) before and after preload-reducing stage 2 palliation. For 31 HLHS
      patients, this study compared global longitudinal strain (S) and strain rate (SR)
      as well as regional peak systolic longitudinal S, SR, and velocity (V) in six RV
      segments on echocardiograms before and after stage 2 surgery. Intraventricular
      dyssynchrony was assessed by calculating the standard deviation of the intervals
      from the beginning of systole to peak S, SR, and V. Global S (-16.7 +/- 5.0 vs 
      15.6 +/- 5.5%) and global SR (-1.2 +/- 0.3 vs -1.2 +/- 0.3 s(-1)) did not change
      after surgery. After surgery, V decreased in the mid lateral segment (2.3 +/- 1.3
      vs 1.7 +/- 0.9 cm/s; p = 0.01) and the basal lateral segment (3.6 +/- 1.1 vs 2.8
      +/- 1.0 cm/s; p = 0.001), whereas S was lower in both of these segments (-19.9%
      +/- 6.0% vs -17.4% +/- 6.3%; p = 0.01 and 20.0 +/- 5.1 vs 15.8 +/- 7.1%; p =
      0.002, respectively). Segmental SR and dyssynchrony did not change. Decreased V
      and S in the RV free wall could be explained by reduced preload of the systemic
      RV after stage 2 palliation.

PMID- 20700589
TI  - Tracheal bronchus: a cause of unexplained prolonged hypoxemia during ventilation.
AB  - The spectrum of disorders involving the tracheobronchial tree is diverse, with
      some of the conditions unique to the pediatric population. Despite the "airway
      first" maxim, many such disorders are missed initially. Tracheal bronchus is one
      such condition that comes to notice by persistent right upper lobe atelectasis,
      pneumothorax, recurrent pneumonia, chronic bronchitis, and prolonged ventilation.
      This anatomic variant in a patient with cyanotic congenital heart disease is
      reported. For this patient, timely identification of tracheal bronchus allowed
      appropriate changes in airway management and was life saving.

PMID- 20700590
TI  - Competitiveness of diverse Methylobacterium strains in the phyllosphere of
      Arabidopsis thaliana and identification of representative models, including M.
      extorquens PA1.
AB  - Facultative methylotrophic bacteria of the genus Methylobacterium are
      consistently found in association with plants, particularly in the phyllosphere.
      To gain a better understanding of the mechanisms underlying the dispersal and
      occurrence of Methylobacterium on plants, diverse strains were isolated,
      identified, and studied with regard to their competitiveness on the model plant
      Arabidopsis thaliana. As a basis for this study a comprehensive collection of
      Methylobacterium isolates was established. Isolates were obtained from five
      different naturally grown A. thaliana populations and diverse other plant genera
      at these and further sites. They were classified using automated ribosomal
      internal spacer analysis (ARISA) and a representative subset was identified based
      on 16S rRNA gene sequence analysis. A comparison of their ARISA patterns with
      those generated based on a cultivation-independent approach from the same
      sampling material confirmed that the isolates were abundant colonizers of the
      studied plants. In competition experiments, colonization efficiency of the
      strains was found to be linked to phylogeny, rather than to the geographical
      origin or plant genus from which they were isolated. The most competitive
      colonizers were related to the species Methylobacterium tardum and
      Methylobacterium extorquens. Higher cell numbers were observed in the
      phyllosphere of A. thaliana when a mixture of different strains was applied
      relative to inoculation with only one strain, suggesting partial niche
      heterogeneity. Based on the results of the competition experiments,
      representative strains with different colonization efficiencies were selected,
      which will serve as models in future studies aiming at a better understanding of
      plant colonization by this bacterial genus. Among them is the meanwhile genome
      sequenced strain M. extorquens PA1, which represents a competitive species of
      plant colonizers with a broad dispersal. This strain was characterized in more
      detail including physiological, morphological, and chemotaxonomical properties.

PMID- 20700591
TI  - The impact of future land use scenarios on runoff volumes in the Muskegon River
      Watershed.
AB  - In this article we compared the response of surface water runoff to a storm event
      for different rates of urbanization, reforestation and riparian buffer setbacks
      across forty subwatersheds of the Muskegon River Watershed located in Michigan,
      USA. We also made these comparisons for several forecasted and one historical
      land use scenarios (over 140 years). Future land use scenarios to 2040 for forest
      regrowth, urbanization rates and stream setbacks were developed using the Land
      Transformation Model (LTM). Historical land use information, from 1900 at 5-year
      time step intervals, was created using a Backcast land use change model
      configured using artificial neural network and driven by agriculture and housing
      census information. We show that (1) controlling the rate of development is the
      most effective policy option to reduce runoff; (2) establishing setbacks along
      the mainstem are not as effective as controlling urban growth; (3) reforestation
      can abate some of the runoff effects from urban growth but not all; (4) land use
      patterns of the 1970s produced the least amount of runoff in most cases in the
      Muskegon River Watershed when compared to land use maps from 1900 to 2040; and,
      (5) future land use patterns here not always lead to increased (worse) runoff
      than the past. We found that while ten of the subwatersheds contained futures
      that were worse than any past land use configuration, twenty-five (62.5%) of the
      subwatersheds produced the greatest amount of runoff in 1900, shortly after the
      entire watershed was clear-cut. One third (14/40) of the subwatersheds contained
      the minimum amount of runoff in the 1960s and 1970s, a period when forest amounts
      were greatest and urban amounts relatively small.

PMID- 20700592
TI  - Utility of the Amplatzer Vascular Plug in splenic artery embolization: a
      comparison study with conventional coil technique.
AB  - PURPOSE: To retrospectively evaluate the role of the Amplatzer Vascular Plug
      (AVP) in proximal splenic artery embolization (SAE) compared with coils.
      MATERIALS AND METHODS: Forty patients had proximal SAE performed with AVP(s) or
      coils as the primary embolic agent for splenic artery steal syndrome (n=23),
      trauma (n=5), portal hypertension (n=5), bleeding due to pancreatic pathology
      (n=4), and pre-splenectomy (n=3). Comparisons were made of occlusion and
      procedure time, cost, and radiation dose. RESULTS: Eighteen proximal SAE
      procedures were successfully performed with AVP. Twenty-two procedures were
      performed with coils, including one failed AVP attempt, which was completed with
      coils. Precise deployment without migration was achieved in all 18 AVP cases.
      Seven of 22 (31.8%) coil procedures had distal migration without consequence.
      There was no statistically significant difference in mean occlusion time (24.4
      min for AVP vs. 31.5 min for coils, P=0.13), procedure time (43.7 min for AVP vs.
      53.8 min for coils, P=0.16), or cost ($1474.13 for AVP vs. $1722.51 for coils,
      P=0.69). There was significant difference in radiation dose (842 mGy for AVP vs.
      1,309 mGy for coils, P=0.04). Fourteen of the 18 (78%) AVP devices required
      additional embolic material. CONCLUSIONS: AVP with additional embolic agents is a
      useful alternative for proximal SAE because of precise deployment, resistance to
      migration, and radiation reduction. AVP use may be limited by vessel tortuosity.
      The occlusion time, procedure time, and cost were reduced but this was not
      statistically significant due to the need for additional embolic material.

PMID- 20700593
TI  - Embolization of hepatic arterial branches to simplify hepatic blood flow before
      yttrium 90 radioembolization: a useful technique in the presence of challenging
      anatomy.
AB  - PURPOSE: In the presence of variant hepatic arterial anatomy, obtaining whole
      liver coverage with yttrium 90 (Y90) radioembolization may be challenging. The
      purpose of this study was to determine whether a technique whereby variant
      hepatic arterial branches are embolized and then Y90 is administered selectively
      into one remaining hepatic arterial branch results in whole-liver coverage and
      effective therapy. A retrospective comparison of treatment response was made
      between a group of patients who underwent this technique before Y90
      administration and a group of patients who received standard Y90 administration
      as a single dose into the proper hepatic artery or in divided doses into the
      immediate hepatic artery branches. The rest of the workup and treatment were
      identical in both groups, including routine embolization of potential nonhepatic,
      nontarget vessels (e.g., the gastroduodenal artery). METHODS: A total of 32
      patients (mean age 56.9 years, range 39-77 years) treated with Y90 between June
      2004 and March 2008 were analyzed. The primary malignancy was colorectal in 29,
      breast in 2, and cholangiocarcinoma in 1. Group 1 comprised 20 patients who had
      no alterations to their hepatic arterial supply. Group 2 comprised 12 cases who
      had undergone prior embolization of hepatic arterial branches before
      administration of Y90. The response to treatment was assessed by comparing
      standardized uptake value (SUV) on the pre- and postprocedure fludeoxyglucose
      positron emission tomographic studies of representative lesions within the right
      and left lobes of the liver. RESULTS: In group 1, significant response (P <
      0.001) was seen among right lobe lesions but not among left lobe lesions (P =
      0.549). In group 2, there was a significant response among both right (P = 0.028)
      and left (P = 0.014) lobe lesions. No difference was found in the response of
      right lobe lesions (P = 0.726) between groups 1 and 2; a significantly greater
      response was found in group 2 compared to group 1 (P = 0.004) for left lobe
      lesions. CONCLUSION: Selective Y90 radioembolization after manipulation of
      hepatic arterial blood supply leads to an even distribution within the entire
      liver. When variations in hepatic arterial anatomy exist, this technique allows
      effective whole-liver radioembolization therapy from a single selective arterial
      injection.

PMID- 20700594
TI  - Does the amount of tagged stool and fluid significantly affect the radiation
      exposure in low-dose CT colonography performed with an automatic exposure
      control?
AB  - OBJECTIVE: To determine whether the amount of tagged stool and fluid
      significantly affects the radiation exposure in low-dose screening CT
      colonography performed with an automatic tube-current modulation technique.
      METHODS: The study included 311 patients. The tagging agent was barium (n = 271)
      or iodine (n = 40). Correlation was measured between mean volume CT dose index
      (CTDI (vol)) and the estimated x-ray attenuation of the tagged stool and fluid
      (ATT). Multiple linear regression analyses were performed to determine the effect
      of ATT on CTDI (vol ) and the effect of ATT on image noise while adjusting for
      other variables including abdominal circumference. RESULTS: CTDI (vol) varied
      from 0.88 to 2.54 mGy. There was no significant correlation between CTDI (vol)
      and ATT (p = 0.61). ATT did not significantly affect CTDI (vol) (p = 0.93), while
      abdominal circumference was the only factor significantly affecting CTDI (vol) (p
      < 0.001). Image noise ranged from 59.5 to 64.1 HU. The p value for the regression
      model explaining the noise was 0.38. CONCLUSION: The amount of stool and fluid
      tagging does not significantly affect radiation exposure.

PMID- 20700595
TI  - Comparative study of covered stent with coil embolization in the treatment of
      cranial internal carotid artery aneurysm: a nonrandomized prospective trial.
AB  - To evaluate whether Willis covered stent implantation yielded angiographic and
      clinical results were better than those with coil embolization. Eighty-nine
      patients with cranial internal carotid artery (CICA) aneurysms were treated
      nonrandomly with covered stents (n = 43, group A) or coil embolization (n = 46,
      group B). Data on the technical success, procedure time, initial and final
      angiographic results, and final clinical outcomes were collected and analyzed at
      >6 months post-procedure. Covered stent placement and coil embolization were
      successful in all patients, except for one patient in group A. The initial
      angiographic results showed complete occlusion in 34 group-A patients (80.9%; 95%
      CI: 69%, 93%) and 24 group-B patients (52.2%; 95% CI: 37%, 67%) (P = 0.004). The
      final angiographic results indicated complete occlusion in 39 group A patients
      (39/41, 95.1%; 95% CI: 88%, 102%) and 22 group B patients (48.9%; 95% CI: 34%,
      64%) (P < 0.001). The average procedure time was shorter in group A than that in
      group B (P < 0.001). CICA aneurysm treatment with covered stents yielded better
      intermediate-term angiographic outcome than those with the recommended approach
      of coil embolization. (ClinicalTrials.gov number, NCT01029938).

PMID- 20700596
TI  - Dectin-1: a role in antifungal defense and consequences of genetic polymorphisms
      in humans.
AB  - The clinical relevance of fungal infections has increased dramatically in recent
      decades as a consequence of the rise of immunocompromised populations, and
      efforts to understand the underlying mechanisms of protective immunity have
      attracted renewed interest. Here we review Dectin-1, a pattern recognition
      receptor involved in antifungal immunity, and discuss recent discoveries of
      polymorphisms in the gene encoding this receptor which result in human disease.

PMID- 20700597
TI  - Mouse chromosome 17 candidate modifier genes for thrombosis.
AB  - Two overlapping quantitative trait loci (QTLs) for clot stability, Hmtb8 and
      Hmtb9, were identified on mouse chromosome 17 in an F2 intercross derived from
      C57BL/6J (B6) and B6-Chr17(A/J) (B6-Chr17) mouse strains. The intervals were in
      synteny with a QTL for thrombotic susceptibility on chromosome 18 in a human
      study, and there were 23 homologs between mouse and human. The objective of this
      study was to determine whether any of these genes in the syntenic region are
      likely candidates as modifiers for clot stability. Seven genes, Twsg1, Zfp161,
      Dlgap1, Ralbp1, Myom1, Rab31, and Emilin2, of the 23 genes with single nucleotide
      polymorphisms (SNPs) in the mRNA-UTR had differential expression in B6 and A/J
      mice. Dlgap1, Ralbp1, Myom1, and Emilin2 also had nonsynonymous SNPs. In
      addition, two other genes had nonsynonymous SNPs, Lama1 and Ndc80. Of these nine
      candidate genes, Emilin2 was selected for further analysis since other EMILIN
      (Elastin Microfibril Interface Located Protein) proteins have known functions in
      vascular structure and coagulation. Differences were found between B6 and A/J
      mice in vessel wall architecture and EMILIN2 protein in plasma, carotid vessel
      wall, and thrombi formed after ferric chloride injury. In B6-Chr17(A/J) mice both
      clot stability and Emilin2 mRNA expression were higher compared to those in B6
      and A/J mice, suggesting the exposure of epistatic interactions. Although other
      homologous genes in the QTL region cannot be ruled out as causative genes,
      further investigation of Emilin2 as a candidate gene for thrombosis
      susceptibility is warranted.

PMID- 20700598
TI  - Environment and feeding change the ability of heart rate to predict metabolism in
      resting Steller sea lions (Eumetopias jubatus).
AB  - The ability to use heart rate (fh) to predict oxygen consumption rates ([Formula:
      see text]) in Steller sea lions and other pinnipeds has been investigated in
      fasting animals. However, it is unknown whether established fh:[Formula: see
      text] relationships hold under more complex physiological situations, such as
      when animals are feeding or digesting. We assessed whether fh could accurately
      predict [Formula: see text] in trained Steller sea lions while fasting and after
      being fed. Using linear mixed-effects models, we derived unique equations to
      describe the fh:[Formula: see text] relationship for fasted sea lions resting on
      land and in water. Feeding did not significantly change the fh:[Formula: see
      text] relationship on land. However, Steller sea lions in water displayed a
      different fh:[Formula: see text] relationship after consuming a 4-kg meal
      compared with the fasting condition. Incorporating comparable published
      fh:[Formula: see text] data from Steller sea lions showed a distinct effect of
      feeding after a 6-kg meal. Ultimately, our study illustrated that both feeding
      and physical environment are statistically relevant when deriving [Formula: see
      text] from telemetered fh, but that only environment affects the practical
      ability to predict metabolism from fh. Updating current bioenergetic models with
      data gathered using these predictive fh:[Formula: see text] equations will yield
      more accurate estimates of metabolic rates of free-ranging Steller sea lions
      under a variety of physiological, behavioral, and environmental states.

PMID- 20700599
TI  - [The "Recommendations for the structure of cardiac pacemaker and defibrillator
      therapy"--what can they achieve?: Implementation of the concept paper for HSM/ICD
      therapy].
AB  - Implantable devices in cardiac electrophysiology have developed from simple
      machines that prevent bradycardia to complex systems that treat malignant
      tachyarrhythmias and severe heart failure. Optimal therapeutic utilization of
      these systems requires profound knowledge of those who treat patients with
      devices. To account for that, the German Cardiac Society has published
      "Recommendations for the structure of cardiac pacemaker and defibrillator
      therapy" to achieve an expertise in 2 levels. These define topics for
      interdisciplinary education to ensure implantation and follow-up of high quality,
      as well as infrastructural requirements such as staff and operation rooms. The
      implementation of these guidelines offers a great opportunity for good quality in
      device therapy and may enhance the results of the compulsory German quality
      registry of the respective institution. The established courses of the German
      Cardiac Society to achieve competence in pacemaker and ICD therapy according to
      the curricula should be complemented by practical training in accredited centers.
      Minimum numbers for implantation and follow-up are necessary to ensure a
      continuously high quality.

PMID- 20700600
TI  - Phenotypic profiling of keloid scars using FT-IR microspectroscopy reveals a
      unique spectral signature.
AB  - Keloid disease (KD) is a quasineoplastic fibroproliferative tumour of unknown
      origin causing a progressive, recurrent dermal lesion. KD is not homogeneous in
      nature and shows phenotypic structural differences between its distinct
      peripheral margins compared to its centre. The keloid margin is often
      symptomatically more active with increased dermal cellularity, compared to a
      symptomatically dormant and hypocellular centre of lesion. The aim of this study
      was to delineate the morphological components of a keloid scar tissue by
      measuring the differences between various anatomical locations within the keloid
      tissue, such as the margin and the centre of the lesion compared to its
      surrounding normal skin using Fourier transform infrared (FT-IR)
      microspectroscopy. FT-IR microspectroscopy is a technique that produces spectra
      with detailed molecular biochemical information inherent of the chemical
      structure. Chemical maps were constructed on extralesional cross sections taken
      from six keloid scars. H&E stained sections were used to confirm diagnosis of
      keloid and orientate the experimental cross sections prior to FT-IR. Spectral
      band assignment and principal components analysis were conducted. Distinct
      vibrational bands (100 spectra) were observed using FT-IR spectroscopy. Partial
      least squares discriminant analysis, with bootstrapping (10,000 analyses),
      identified whether a spectrum was from the keloid or normal tissue showing an
      average accuracy of 84.8%, precision of 80.4%, specificity of 76.2%, and
      sensitivity of 92.9%. FT-IR microspectroscopy showed significant differences in
      spectral profiles in keloid tissue in different anatomical locations within the
      cross section. We believe that this proof-of-concept study may help substantiate
      the use of FTIR spectroscopy in keloid diagnosis and prognosis.

PMID- 20700601
TI  - Gender-related features of persistent delusional disorders.
AB  - This paper presents gender-related features of Delusional Disorder. It is part of
      the Halle Delusional Syndromes Study (HADES-Study). All inpatients fulfilling the
      DSM-IV/ICD-10 criteria of Delusional Disorder/Persistent Delusional Disorder (DD)
      during a 14-year period were included and followed up for an average of 10.8
      years. Gender distribution was almost equal, women became ill significantly later
      than men, and almost all women had a stable diagnosis-in contrast to men. The
      great majority of women, at the end of the follow-up period, had an unremitted
      DD. Women more frequently had low social functioning at admission, but then were
      more compliant and received more frequently pharmacological medication. There
      were no differences in the delusional topic and no differences regarding long
      term disability and autarky. In spite of previous reports, the HADES-Study found
      no gender difference in the frequency of DD. However, men tended more frequently
      to change into schizophrenia and schizoaffective disorder. In these cases, the DD
      might have been a prodrome of schizophrenia or schizoaffective disorder, which
      manifests later in life. Although in both female and male DD patients, the
      majority remained unremitted, almost none of them lost their autarky (independent
      living). While women more frequently received psychopharmacological medication,
      their DD was usually found to be unremitted.

PMID- 20700602
TI  - Skin blood flow differentially affects near-infrared spectroscopy-derived
      measures of muscle oxygen saturation and blood volume at rest and during dynamic
      leg exercise.
AB  - The impact of skin blood flow changes on near-infrared spectroscopy (NIRS)
      derived measures of muscle oxygen saturation (SmO(2)) and blood volume has not
      been fully established. We measured SmO(2) and total hemoglobin concentration
      ([tHb]) responses of the right vastus lateralis during rest and dynamic knee
      extension exercise in ten young, healthy males. The protocol was repeated four
      times: twice without thigh heating for reliability, and twice with different
      grades of thigh heating for assessing the impact of cutaneous vasodilation on
      SmO(2) and Delta[tHb]. The reliability of our SmO(2) and [tHb] measurements was
      good. Thigh heating at 37 and 42 degrees C caused marked increases in cutaneous
      vascular conductance (CVC) during rest and exercise (P < 0.001 between each
      condition), and small increases in SmO(2) during rest (from 69 +/- 8% to 71 +/-
      7% and 73 +/- 6%, respectively; P < 0.05 between each condition), but not during
      exercise (e.g. 1 min exercise: 51 +/- 11% vs. 51 +/- 11% and 52 +/- 11%,
      respectively; P > 0.05 at all time points). In contrast, heating-induced
      increases in %CVC(peak) were accompanied by increases in [tHb] at rest and during
      exercise and a decrease in Delta[tHb] during exercise (all P < 0.05). Our
      findings suggest that NIRS-derived measures of SmO(2) and blood volume are
      differentially affected by skin blood flow at rest and during exercise. The
      findings from this study should be considered in NIRS experiments where skin
      blood flow can change markedly (e.g. high-intensity and/or prolonged exercise).

PMID- 20700603
TI  - Intraoperative laser fluorescence angiography in colorectal surgery: a
      noninvasive analysis to reduce the rate of anastomotic leakage.
AB  - PURPOSE: Up to 19% of all colorectal resections develop clinically apparent
      insufficiencies. Insufficient perfusion of the anastomosis is recognized as an
      important risk factor. As tissue perfusion can be objectified intraoperatively
      using laser fluorescence angiography (LFA), its effect on the rate of anastomotic
      complications was evaluated in a retrospective matched-pairs analysis. METHODS:
      Between 2003 and 2008, all anastomosis or resection margins in colorectal cancer
      resections were investigated intraoperatively using LFA (LFA group). Patients
      with colorectal cancer resections between 1998 and 2003 without LFA served as the
      control group. Four hundred two patients were matched for age, T-stage, type of
      resection and anastomosis, defunctioning stoma, administration of blood,
      emergency conditions, and body mass index. Statistical analysis was performed
      using the Fisher and the Wilcoxon tests. RESULTS: Twenty-two surgical revisions
      were necessary due to anastomotic leakage, seven (3.5%) in the LFA group and 15
      (7.5%) in the control group. Subgroup analysis revealed that in elective
      resections the rate of revision was 3.1% (LFA group) and 7.7% (control group) (p
      = 0.04, risk of revision (ROR) reduced by 60%). In patients older than 70 years,
      the rate of revision was 4.3% (LFA group) compared to 11.9% (control group) (p =
      0.04, ROR reduced by 64%). After hand-sewn anastomosis, the rate of revision was
      1.2% (LFA group) and 8.5% (control group) (p = 0.03, ROR reduced by 84%).
      Hospital stay was significantly reduced in the LFA group (Wilcoxon test; p =
      0.01). CONCLUSION: There was an overall reduction in the absolute revision rate
      of 4% in the LFA group and a significantly reduced rate of revision in the
      subgroup analysis of patients undergoing elective colorectal resections, in
      patients older than 70 years and in patients with hand-sewn anastomosis. This
      demonstrates that LFA is a method that may significantly reduce not only the rate
      of severe complications in colorectal surgery but also the hospital length of
      stay.

PMID- 20700604
TI  - Clinical, laboratory and pathological findings in dogs experimentally infected
      with Angiostrongylus vasorum.
AB  - The aim of this comparative study was to investigate the development of clinical
      signs and accompanying haematological, coproscopic and pathological findings as a
      basis for the monitoring of health condition of Angiostrongylus vasorum infected
      dogs. Six beagles were orally inoculated with 50 (n=3) or 500 (n=3) A. vasorum
      third stage larvae (L3) obtained from experimentally infected Biomphalaria
      glabrata snails. Two dogs were treated with moxidectin/imidacloprid spot-on
      solution and two further dogs with an oral experimental compound 92 days post
      infection (dpi), and were necropsied 166 dpi. Two untreated control dogs were
      necropsied 97 dpi. Prepatency was 47-49 days. Dogs inoculated with 500 L3
      exhibited earlier (from 42 dpi) and more severe respiratory signs. Clinical signs
      resolved 12 days after treatment and larval excretion stopped within 20 days in
      all four treated dogs. Upon necropsy, 10 and 170 adult worms were recovered from
      the untreated dogs inoculated with 50 and 500 L3, respectively. Adult worms were
      also found in two treated dogs, in the absence of L1 or eggs. Despite heavy A.
      vasorum infection load and severe pulmonary changes including vascular
      thrombosis, only mild haematological changes were observed. Eosinophilia was
      absent but the presence of plasma cells was observed. Neutrophilic leucocytes
      showed a transient increase but only after treatment. Signs for coagulopathies
      were slight; nevertheless coagulation parameters were inoculation dose dependent.
      Ten weeks after treatment pulmonary fibrosis was still present. Infections
      starting from 50 L3 of A. vasorum had a massive impact on lung tissues and
      therefore on the health of affected dogs, particularly after prepatency, although
      only mild haematological abnormalities were evident.

PMID- 20700606
TI  - Continuous culture and proteomic analysis of Escherichia coli DH5alpha and its
      acetate-tolerant mutant DA19 under conditions of nitrogen source limitation.
AB  - Escherichia coli DH5alpha grows poorly in a chemically defined medium, but its
      acetate-tolerant mutant, DA19, grows fast and produces less acetate. To
      investigate the differences in metabolism between the two strains, the samples of
      continuous cultures at steady state were analyzed by two-dimensional SDS-PAGE (2
      D SDS-PAGE) and peptide mass fingerprinting (PMF). The results indicated that in
      DA19, expression of gnd, yddS, and purH (except for adenine supplement) was up
      regulated, and expression of atpA, glnK, and ompR, which encode membrane
      proteins, was significantly up-regulated. Expression of ackA and yahK in DA19 was
      down-regulated. In the presence of acetate, hchA and ydcW in DH5alpha were
      significantly down-regulated. This study shed light on the differences in
      metabolic properties between DH5alpha and DA19, and provided some ideas for
      improving strains through metabolic engineering.

PMID- 20700605
TI  - Transcription regulation of the Escherichia coli pcnB gene coding for poly(A)
      polymerase I: roles of ppGpp, DksA and sigma factors.
AB  - Poly(A) polymerase I (PAP I), encoded by the pcnB gene, is a major enzyme
      responsible for RNA polyadenylation in Escherichia coli, a process involved in
      the global control of gene expression in this bacterium through influencing the
      rate of transcript degradation. Recent studies have suggested a complicated
      regulation of pcnB expression, including a complex promoter region, a control at
      the level of translation initiation and dependence on bacterial growth rate. In
      this report, studies on transcription regulation of the pcnB gene are described.
      Results of in vivo and in vitro experiments indicated that (a) there are three
      sigma(70)-dependent (p1, pB, and p2) and two sigma(S)-dependent (pS1 and pS2)
      promoters of the pcnB gene, (b) guanosine tetraphosphate (ppGpp) and DksA
      directly inhibit transcription from pB, pS1 and pS2, and (c) pB activity is
      drastically impaired at the stationary phase of growth. These results indicate
      that regulation of the pcnB gene transcription is a complex process, which
      involves several factors acting to ensure precise control of PAP I production.
      Moreover, inhibition of activities of pS1 and pS2 by ppGpp and DksA suggests that
      regulation of transcription from promoters requiring alternative sigma factors by
      these effectors of the stringent response might occur according to both passive
      and active models.

PMID- 20700607
TI  - Study of aldehyde oxidase-catalyzed metabolic pathway of phenanthridine using MCR
      ALS method.
AB  - Evaluation of metabolic pathways is one of the challenging areas in biological
      and pharmaceutical sciences. Phenanthridine oxidation to phenanthridinone is used
      commonly to study aldehyde oxidase activity. This reaction could pass through
      phenanthridine N-oxide intermediate. In the present study, the application of
      multivariate curve resolution, optimized by alternating least squares (MCR-ALS)
      to investigate this metabolic pathway has been described. The results obtained
      from MCR-ALS analysis along with those obtained from the use of potassium
      ferrocyanide method indicated that phenanthridine is directly oxidized to
      phenanthridinone by rat liver aldehyde oxidase without passing through
      phenanthridine N-oxide intermediate. It was also found that the later compound is
      not metabolized by this enzyme.

PMID- 20700608
TI  - Endoscopic nasobiliary drainage is the most suitable preoperative biliary
      drainage method in the management of patients with hilar cholangiocarcinoma.
AB  - BACKGROUND: Controversy exists over the preferred technique of preoperative
      biliary drainage (PBD) in patients with hilar cholangiocarcinoma (HCA). The goal
      of this retrospective study was to identify the preferred technique of PBD for
      HCA. METHODS: A total of 128 consecutive patients with HCA diagnosed between
      September 1999 and December 2009 who underwent PBD were included in this study.
      The study compared outcomes of endoscopic nasobiliary drainage (ENBD), endoscopic
      biliary stenting (EBS), and percutaneous transhepatic biliary drainage (PTBD) in
      patients with HCA. RESULTS: There were no significant differences in preoperative
      laboratory data, rates of major hepatectomy, or decompression periods among the 3
      groups. Complications were significantly more frequent in the EBS group compared
      with either the ENBD or PTBD group (p < 0.05). Drainage tube occlusion with
      cholangitis was significantly more common in the EBS group compared with either
      the ENBD or PTBD group (p < 0.0001). Patients in the PTBD group experienced
      serious complications including vascular injury (8%) and cancer dissemination
      (4%). Patients in the ENBD and EBS groups had mild post-endoscopic retrograde
      cholangiopancreatography pancreatitis (5%). Conversion procedures were
      significantly more common in the EBS group compared with the ENBD and PTBD groups
      (p < 0.05). There was no significant difference in postsurgical morbidity or
      mortality among the 3 groups. CONCLUSIONS: Drainage tube occlusion with
      cholangitis was a frequent complication associated with EBS. PTBD was associated
      with serious complications such as vascular injury and cancer dissemination. ENBD
      was found to be the most suitable method for initial PBD management in patients
      with HCA.

PMID- 20700609
TI  - Horizontal body and trunk center of mass offset and standing balance in scoliotic
      girls.
AB  - In adolescent idiopathic scoliotic girls, postural imbalance is attributed to a
      sensory rearrangement of the motor system on the representation of the body in
      space. The objectives of this study were to test if the anteroposterior (AP),
      mediolateral (ML) and resultant body-head and trunk center of mass (COM)
      horizontal offsets were similar in able-bodied and scoliotic girls and if these
      offsets were related to the center of pressure displacements. A total of 21
      adolescent idiopathic scoliosis girls and 20 able-bodied girls participated in
      this study. Their body COM position and that of the head and trunk were estimated
      according to Damavandi et al. (Med Eng Phys 31:1187-1194, 2009). The COP range
      and speed in both AP and ML axes were calculated from force plate measurements in
      quiet standing. The AP offset of the able-bodied group was anterior to the body
      COM by 11.0 +/- 15.9 mm, while that of the scoliotic group was posterior to it by
      -17.3 +/- 11.2 mm. The able-bodied group maintained their head-trunk segment COM
      more to the right by 14.1 +/- 13.1 mm, while that of the scoliotic group was
      nearly over their body centerline. The scoliotic girls presented higher values
      for COP range and COP speed than the able-bodied girls. The resultant COM offset
      was correlated with both the ML COP range and speed only for the scoliotic girls.
      The small ML COM offset in the scoliotic girls was attributed to a compensatory
      action of the spinal deformity in the frontal plane resulting in a backward
      resultant COM offset to regain postural balance concomitant to an increase in the
      ML neuromuscular demand.

PMID- 20700610
TI  - Expert's comment concerning Grand Rounds case entitled "Posterior listhesis of a
      lumbar vertebra in spinal tuberculosis" (by Matthew A. Kirkman and Krishnamurthy
      Sridhar).

PMID- 20700611
TI  - Coronal deformity correction in adolescent idiopathic scoliosis patients using
      the fulcrum-bending radiograph: a prospective comparative analysis of the
      proximal thoracic, main thoracic, and thoracolumbar/lumbar curves.
AB  - The aim of the prospective, comparative radiographic analysis was to determine
      the role of the fulcrum-bending radiograph (FBR) for the assessment of the
      proximal thoracic (PT), main thoracic (MT), and the thoracolumbar/lumbar (TL/L)
      curves in patients undergoing posterior spinal pedicle screw fixation and fusion
      for adolescent idiopathic scoliosis (AIS). The FBR demonstrated statistically
      better correction than other preoperative methods for the assessment of frontal
      plane correction of the MT curves. The fulcrum-bending correction index (FBCI)
      has been considered a superior method than the correction rate for comparing
      curve correction undergoing posterior spinal fusion because it accounts for the
      curve flexibility. However, their applicability to assess the PT and TL/L curves
      in AIS patients remains speculative. The relation between FBR and correction
      obtained by pedicle screws fixation is still unknown. Thirty-eight consecutive
      AIS patients who underwent pedicle screw fixation and posterior fusion were
      included in this study. The assessment of preoperative radiographs included
      standing posterior-anterior (PA), FBR, supine side-bending, and postoperative
      standing PA and lateral plain radiographs. The flexibility of the curve, as well
      as the FBCI, was calculated for all patients. Postoperatively, radiographs were
      assessed at immediate (i.e. 1 week), 3-month, 6-month, 12-month, and 2-year
      follow-up. Cobb angles were obtained from the PT, MT, and TL/L curves. The study
      consisted of 9 PT, 37 MT, and 12 TL/L curves, with a mean age of 15.1 years. The
      mean FBR flexibility of the PT, MT, and the TL/L curves was 42.6, 61.1, and
      66.2%, respectively. The mean operative correction rates in the PT, MT, and TL/L
      curves were 43.4, 69.3, and 73.9%, respectively, and the mean FBCI was 103.8,
      117.0, and 114.8%, respectively. Fulcrum-bending flexibility was positively
      correlated with the operative correction rate in PT, MT, and TL/L curves.
      Although the correction rate in MT and TL/L curves was higher than PT curves, the
      FBCI in PT, MT, and TL/L curves was not significantly different (p < 0.05). The
      FBR can be used to assist in the assessment of PT, MT, and TL/L curve corrections
      in AIS patients. When curve flexibility is taken into account by FBR, the ability
      of pedicle screws to correct PT, MT, and TL/L curves is the same.

PMID- 20700613
TI  - TAK-778 induces osteogenesis in ovariectomized rats via an estrogen receptor
      dependent pathway.
AB  - TAK-778, a derivative of ipriflavone, has been shown to induce bone growth both
      in vitro and in vivo. Recently, it has been shown that TAK-778 can enhance
      osteoblast differentiation of human bone marrow cells via an estrogen receptor
      (ER)-dependent pathway. However, the mechanism by which TAK-778 exerts its effect
      in vivo has not been determined. Considering the evidence that TAK-778 acts via
      ER-mediated signaling in vitro, in the present study we tested if TAK-778 induced
      osteogenesis via an ER-dependent pathway using an ovariectomized (OVX) rat model.
      Two weeks after test animals underwent ovariectomy, TAK-778 and/or tamoxifen was
      administered orally over 3 months. Vehicle-treated and sham-operated rats served
      as controls. The bone mineral density (BMD) of the lumbar vertebrae and sagittal
      two-dimensional images of the L3 vertebral body were measured. In addition, bone
      formation rates (BFR) and serum calcium and osteocalcin levels were measured. The
      results indicated that TAK-778 significantly increased BMD, serum calcium and
      osteocalcin levels, and BFR when compared to that of the vehicle-treated group.
      However, tamoxifen, a well-known ER antagonist, clearly inhibited the increase in
      these parameters induced by TAK-778. In addition, micro-computed tomography scans
      showed that treatment with TAK-778 increased the structure model index, bone
      volume/tissue volume, and trabecular thickness parameters and decreased the
      trabecular separation/spacing in OVX rats. Tamoxifen suppressed these effects
      when administered in combination with TAK-778. Taken together, the present study
      showed that TAK-778 enhanced bone formation in OVX rats and that this effect was
      dependent on an ER-mediated pathway.

PMID- 20700612
TI  - Neuroprotective effect of Spirulina in cerebral ischemia-reperfusion injury in
      rats.
AB  - Epidemiological studies indicate that the intake of Mediterranean-style diet is
      inversely associated with risk of stroke, cardiovascular diseases, and cancer.
      Spirulina is widely used nutritional supplement rich in proteins and
      antioxidants. Evidence demonstrates that the impaired energy metabolism and the
      excessive generation of reactive oxygen radicals contribute to the brain injury
      associated with cerebral ischemia. In the present study, the protective effect of
      Spirulina was investigated in transient middle cerebral artery occlusion (MCAO)
      induced focal cerebral ischemia-reperfusion injury in rats. Male albino rats were
      divided into six groups: control, sham-operated group, ischemic control group,
      and Spirulina-pretreated groups (45, 90 and 180 mg/kg/p.o.). Spirulina was
      administered once a day, for 7 days. The rats were subjected to a 2-h right MCAO
      via the intraluminal filament technique and 22 h of reperfusion. Pretreatment
      with Spirulina significantly reduced the histological changes and neurological
      deficits. Spirulina at a dose of 180 mg/kg significantly reversed the elevated
      brain malondialdehyde (MDA) content and restored the decreased activities of
      brain superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH)
      indicating that Spirulina has the protective potential against cerebral ischemia
      injury and its protective effects may be due to its antioxidant property.

PMID- 20700614
TI  - Prevalence and characteristics of ertapenem-nonsusceptible Escherichia coli in a
      Taiwanese university hospital, 1999 to 2007.
AB  - The present study was conducted to investigate the prevalence and characteristics
      of ertapenem-nonsusceptible (ETP-NS) Escherichia coli in a Taiwanese university.
      A total of 9,722 isolates collected in 1999, 2003, 2005, and 2007 were examined.
      Overall, 1.0% of all isolates from 66 patients were interpreted as ETP-NS on the
      basis of the disk diffusion test result. Most of these isolates were clonally
      unrelated and showed low-level ertapenem resistance, the production of CMY-2
      cephalosporinase (86.4%), and decreased expression of the OmpF (97.0%) and/or
      OmpC (56.1%) porins. No carbapenemase was detected. The decreased porin
      expression was associated with disruptions of ompF or ompC in only about one
      third of the ETP-NS isolates. During the study period, the prevalence of ETP-NS
      strains increased from 0.1 to 1.7%, accompanying an increase (0.8 to 17.6%) in
      the prevalence of CMY-2 producers. Coexistent or pre-existing clonally related
      ertapenem-susceptible (ETP-S) E. coli isolates were identified in 47.0% of all
      case patients, and almost all of the ETP-S isolates had the same beta-lactamases
      as the ETP-NS isolates. Our study results suggest the restricted use of extended
      spectrum cephalosporins to hinder the emergence and prevalence of carbapenem
      resistance in E. coli, which may arise by the accumulation of multiple resistance
      determinants.

PMID- 20700615
TI  - Review of primary unknown cancer: cases referred to the National Cancer Center
      Hospital East.
AB  - BACKGROUND: Primary unknown cancer (PUC) is not rare neoplasm. The clinical
      features and survival time of these patients are heterogeneous. We analyzed cases
      that were referred to the National Cancer Center Hospital East with preliminary
      diagnosed PUC to evaluate the natural history and clinical features. METHODS: We
      retrospectively reviewed medical records of PUC patients who were referred to our
      institution between August 2005 and December 2008. RESULTS: One hundred and
      twenty-six patients with preliminary diagnoses of PUC were referred to the
      National Cancer Center Hospital East from community hospitals. The median age was
      63 years (range 31-89 years). Almost all patients (85.7%) had good performance
      status (0-1). The mean interval between the first visit to a community hospital
      and referral to our hospital was 3.66 months (range 0-60 months). In 41 patients
      (32.5%), primary malignancies were identified by immunohistochemical studies and
      radiographical workup after referral to our hospital. Twenty-eight patients
      (22.2%) were defined as belonging to favorable subsets. About 50% of patients
      with unfavorable subsets received chemotherapy. None of the patients were
      autopsied. CONCLUSION: In about half of the patients with preliminary diagnosed
      PUC, the primary origin could be identified, or it was possible to distinguish
      subsets with favorable prognosis.

PMID- 20700616
TI  - Our criteria for PPH procedure in one day surgery practice.
AB  - BACKGROUND: The aim of this report is to analyse our results and to underline our
      criteria for day surgery practice. PATIENTS AND METHODS: Our patients are
      selected according to ASA criteria. Occasionally, the patients with some risk
      factors are selected but only when their concomitant diseases are well
      controlled. RESULTS: We have treated 673 patients with the third and early fourth
      degree haemorrhoids. We have had patients with several minor problems causing no
      influence on the success of the procedure. Good haemostasis, preventing
      postoperative bleeding, is the most important factor. CONCLUSION: Among
      proctological procedures in haemorrhoid treatment, the PPH technique has firm and
      well-accepted position even in ambulatory surgery.

PMID- 20700617
TI  - Metachronous colorectal cancer.
AB  - AIM: In this study, we present our patients with metachronous colorectal cancer.
      PATIENTS AND METHODS: In the period between 1990 and 2009, 670 patients with
      colorectal cancer were treated. RESULTS: Metachronous cancer was developed in 4
      (0.6%) patients. The time interval between index and metachronous cancer was 28
      months to 22 years (mean 146 months). CONCLUSION: Metachronous colorectal cancer
      is a potential risk that proves the necessity of postoperative colonoscopic
      control of all patients with colorectal cancer.

PMID- 20700618
TI  - Clinicopathological differences between right- and left-sided colonic tumors and
      impact upon survival.
AB  - AIM: This study is to analyze the clinicopathological differences between right-
      and left-sided colonic tumors and to evaluate the impact upon the patient's
      survival. METHODS: In a period of 5 years (2004-2009), 453 patients were
      diagnosed with colorectal cancer. RESULTS: From a total of 453 patients diagnosed
      with colon cancer, 56.5% of them were men, while 43.5% of them were women. Right
      sided colonic tumors were diagnosed in 54.53% of the patients compared to the
      45.47% of patients with left-sided colonic tumors. The size of colonic tumors is
      statistically significant greater in right-sided colonic tumors compared to left
      ones (P < 0.001). Left-sided colon cancer patients identified to have a
      statistically significant better overall 5-year survival rate compared to right
      sided ones (P < 0.001). CONCLUSION: Based upon our results, there is a different
      biological profile between right- and left-sided colonic tumors.

PMID- 20700619
TI  - Anastomotic leakage after colonic resection.
AB  - The aim of this study is to present the diagnosis and management of anastomotic
      leakage after colon resection. Early diagnosis and urgent therapeutic
      intervention are required in order to avert life-threatening conditions that may
      be caused by anastomotic leakage. Minor leaks can be managed conservatively with
      successful outcomes. Major leaks should be managed operatively. In conclusion,
      leakage of colonic anastomosis remains the most serious complication after colon
      resection.

PMID- 20700620
TI  - Clinical effects of calcium channel blockers and renin-angiotensin-aldosterone
      system inhibitors on changes in the estimated glomerular filtration rate in
      patients with polycystic kidney disease.
AB  - BACKGROUND: In the tubular cells of patients with polycystic kidney disease
      (PKD), a reduced intracellular Ca(2+) level accelerates cell proliferation,
      resulting in cyst formation. Thus, whether calcium channel blockers (CCB) are
      useful for the treatment of hypertension in patients with PKD is questionable.
      METHODS: Thirty-two outpatients with autosomal dominant PKD (ADPKD) were treated
      at Tokyo Women's Medical University between 2003 and 2008; these patients were
      studied retrospectively. Periods during which the antihypertensive drug
      prescriptions for CCB and/or renin-angiotensin-aldosterone system inhibitors
      (RAAS-I; including angiotensin converting enzyme inhibitor and angiotensin II
      receptor blocker) had not been changed for at least 1 year and during which time
      a diuretic agent had not been prescribed were selected from among the clinical
      histories of the 32 outpatients. Consequently, 31 periods of 31 patients were
      analyzed, and mean treatment duration was 2.4 years in this study. The estimated
      glomerular filtration rate (eGFR) was used to evaluate renal function. To
      evaluate the influence of CCB and RAAS-I with respect to the decrease of the
      eGFR, analysis of covariance (ANCOVA), including confounding factors [baseline
      eGFR, mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP)],
      was used. Only CCB significantly contributed to a reduction in ?eGFR in both a
      univariable ANCOVA and a multivariable ANCOVA. None of the confounding factors,
      RAAS-I, the baseline eGFR, or blood pressure, contributed to reductions in ?eGFR.
      CONCLUSION: These results suggest that from a renoprotective perspective, CCB
      should possibly be avoided in patients with PKD unless treatment for resistant
      hypertension is necessary.

PMID- 20700621
TI  - Chronic Kidney Disease Japan Cohort study: baseline characteristics and factors
      associated with causative diseases and renal function.
AB  - BACKGROUND: Prevalence of chronic kidney disease (CKD) is estimated to be 13.3
      million in Japan, but patient characteristics during the predialysis period (CKD
      stages 3-5) are not well studied. METHODS: We established the Chronic Kidney
      Disease Japan Cohort (CKD-JAC) to study the incidence of cardiovascular disease
      (CVD), end-stage renal disease (ESRD), and all-cause mortality in predialysis
      patients treated by nephrologists for 4 years. The inclusion criteria were (1)
      Japanese and Asian patients living in Japan, (2) age 20-75 years, and (3)
      estimated glomerular filtration rate (eGFR) 10-59 ml/min/1.73 m(2). RESULTS: We
      analyzed 2977 participants for baseline characteristics. Mean eGFR was 28.6 +/-
      11.8 ml/min/1.73 m(2), and mean albuminuria was 976 +/- 1340 mg/g Cr. In our
      study, 91.9% of participants had hypertension, but it was well controlled (131/76
      mmHg). Angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor
      blockers (ARBs) were used by most participants. Less than 15% of participants had
      history of ischemic heart disease, and 11.5% had history of stroke. Heart failure
      and arteriosclerosis obliterans were present in 3.9% and 3.6% of patients,
      respectively. Indicators of arteriosclerosis, higher pulse wave velocity (PWV),
      and high pulse pressure were associated with diabetes and particularly with
      diabetic nephropathy. Patients included due to glomerulonephritis seemed to be at
      low risk for atherosclerosis and also to show lower levels of hypertension.
      CONCLUSIONS: The difference between causative diseases is associated with
      different comorbidity and level of arteriosclerosis. Future analysis of the
      cohort will clarify whether incidence of ESRD and CVD differs among causative
      diseases.

PMID- 20700622
TI  - Self-eating for death or survival during cisplatin nephrotoxicity?

PMID- 20700623
TI  - A direct numerical simulation method for complex modulus of particle dispersions.
AB  - We report an extension of the smoothed profile method (SPM) (Y. Nakayama, K. Kim,
      and R. Yamamoto, Eur. Phys. J. E 26, 361 (2008)), a direct numerical simulation
      method for calculating the complex modulus of the dispersion of particles, in
      which we introduce a temporally oscillatory external force into the system. The
      validity of the method was examined by evaluating the storage G'(omega) and loss
      G"(omega) moduli of a system composed of identical spherical particles dispersed
      in an incompressible Newtonian host fluid at volume fractions of Phi = 0 , 0.41,
      0.46, and 0.51. The moduli were evaluated at several frequencies of shear flow;
      the shear flow used here has a zigzag profile, as is consistent with the usual
      periodic boundary conditions. The simulation results were compared with several
      experiments for colloidal dispersions of spherical particles.

PMID- 20700624
TI  - Contact models of repaired articular surfaces: influence of loading conditions
      and the superficial tangential zone.
AB  - The superficial tangential zone (STZ) plays a significant role in normal
      articular cartilage's ability to support loads and retain fluids. To date, tissue
      engineering efforts have not replicated normal STZ function in cartilage repairs.
      This finite element study examined the STZ's role in normal and repaired
      articular surfaces under different contact conditions. Contact area and pressure
      distributions were allowed to change with time, tension-compression nonlinearity
      modeled collagen behavior in the STZ, and nonlinear geometry was incorporated to
      accommodate finite deformation. Responses to loading via impermeable and
      permeable rigid surfaces were compared to loading via normal cartilage, a more
      physiologic condition, anticipating the two rigid loading surfaces would bracket
      that of normal. For models loaded by normal cartilage, an STZ placed over the
      inferior repair region reduced the short-term axial compression of the articular
      surface by 15%, when compared to a repair without an STZ. Covering the repair
      with a normal STZ shifted the flow patterns and strain levels back toward that of
      normal cartilage. Additionally, reductions in von Mises stress (21%) and an
      increase in fluid pressure (13%) occurred in repair tissue under the STZ. This
      continues to show that STZ properties of sufficient quality are likely critical
      for the survival of transplanted constructs in vivo. However, response to loading
      via normal cartilage did not always fall within ranges predicted by the rigid
      surfaces. Use of more physiologic contact models is recommended for more accurate
      investigations into properties critical to the success of repair tissues.

PMID- 20700625
TI  - Bone marrow-derived mesenchymal cells and MMP13 contribute to experimental
      choroidal neovascularization.
AB  - In this study, we evaluate the potential involvement of collagenase-3 (MMP13), a
      matrix metalloproteinase (MMP) family member, in the exudative form of age
      related macular degeneration characterized by a neovascularisation into the
      choroid. RT-PCR analysis revealed that human neovascular membranes issued from
      patients with AMD expressed high levels of Mmp13. The contribution of MMP13 in
      choroidal neovascularization (CNV) formation was explored by using a murine model
      of laser-induced CNV and applying it to wild-type mice (WT) and Mmp13-deficient
      mice (Mmp13 ( -/- ) mice). Angiogenic and inflammatory reactions were explored by
      immunohistochemistry. The implication of bone marrow (BM)-derived cells was
      determined by BM engraftment into irradiated mice and by injecting mesenchymal
      stem cells (MSC) isolated from WT BM. The deficiency of Mmp13 impaired CNV
      formation which was fully restored by WT BM engraftment and partially rescued by
      several injections of WT MSC. The present study sheds light on a novel function
      of MMP13 during BM-dependent choroidal vascularization and provides evidence for
      a role for MSC in the pathogenesis of CNV.

PMID- 20700626
TI  - Deactivation of snares by wild chimpanzees.
AB  - Snare injuries to chimpanzees (Pan troglodytes) have been reported at many study
      sites across Africa, and in some cases cause the death of the ensnared animal.
      However, very few snare injuries have been reported concerning the chimpanzees of
      Bossou, Guinea. The rarity of snare injuries in this study group warrants further
      consideration, given the exceptionally close proximity of the Bossou chimpanzees
      to human settlements and the widespread practice of snare hunting in the area.
      Herein we report a total of six observations of chimpanzees attempting to break
      and deactivate snares, successfully doing so on two of these occasions. We
      observed the behavior in 5 males, ranging in age from juveniles to adults. We
      argue that such active responses to snares must be contributing to the rarity of
      injuries in this group. Based on our observations, we suggest that the behavior
      has transmitted down the group. Our research team at Bossou continues to remove
      snares from the forest, but the threat of ensnarement still remains. We discuss
      potential ways to achieve a good balance between human subsistence activities and
      the conservation of chimpanzees at Bossou, which will increasingly be an area of
      great concern in the future.

PMID- 20700627
TI  - Functional characterization of two chimeric proteins between a Petunia inflata S
      locus F-box protein, PiSLF2, and a PiSLF-like protein, PiSLFLb-S2.
AB  - Self-incompatible solanaceous species possess the S-RNase and SLF (S-locus F-box)
      genes at the highly polymorphic S-locus, and their products mediate S-haplotype
      specific rejection of pollen tubes in the style. After a pollen tube grows into
      the style, the S-RNases produced in the style are taken up; however, only self S
      RNase (product of the matching S-haplotype) can inhibit the subsequent growth of
      the pollen tube. Based on the finding that non-self interactions between PiSLF
      (Petunia inflata SLF) and S-RNase are stronger than self-interactions, and based
      on the biochemical properties of PiSLF, we previously proposed that a PiSLF
      preferentially interacts with its non-self S-RNases to mediate their
      ubiquitination and degradation, thereby only allowing self S-RNase to exert its
      cytotoxic function. We further divided PiSLF into three potential Functional
      Domains (FDs), FD1-FD3, based on sequence comparison of PiSLF and PiSLF-like
      proteins, and based on S-RNase-binding properties of these proteins and various
      truncated forms of PiSLF(2) (S(2) allelic variant of PiSLF). In this work, we
      examined the in vivo function of FD2, which we proposed to be responsible for
      strong, general interactions between PiSLF and S-RNase. We swapped FD2 of
      PiSLF(2) with the corresponding region of PiSLFLb-S(2) (S(2) allelic variant of a
      PiSLF-like protein), and expressed GFP-fused chimeric proteins, named b-2-b and 2
      b-2, in S(2) S(3) transgenic plants. We showed that neither chimeric protein
      retained the SI function of PiSLF(2), suggesting that FD2 is necessary, but not
      sufficient, for the function of PiSLF. Moreover, since we previously found that b
      2-b and 2-b-2 only interacted with S(3)-RNase ~50 and ~30%, respectively, as
      strongly as did PiSLF(2) in vitro, their inability to function as PiSLF(2) is
      also consistent with our model predicating on strong interaction between a PiSLF
      and its non-self S-RNases as part of the biochemical basis for S-haplotype
      specific rejection of pollen tubes.

PMID- 20700628
TI  - Knock-down of the COX3 and COX17 gene expression of cytochrome c oxidase in the
      unicellular green alga Chlamydomonas reinhardtii.
AB  - The COX3 gene encodes a core subunit of mitochondrial cytochrome c oxidase
      (complex IV) whereas the COX17 gene encodes a chaperone delivering copper to the
      enzyme. Mutants of these two genes were isolated by RNA interference in the
      microalga Chlamydomonas. The COX3 mRNA was completely lacking in the cox3-RNAi
      mutant and no activity and assembly of complex IV were detected. The cox17-RNAi
      mutant presented a reduced level of COX17 mRNA, a reduced activity of the
      cytochrome c oxidase but no modification of its amount. The cox3-RNAi mutant had
      only 40% of the wild-type rate of dark respiration which was cyanide-insensitive.
      The mutant presented a 60% decrease of H(2)O(2) production in the dark compared
      to wild type, which probably accounts for a reduced electron leakage by
      respiratory complexes III and IV. In contrast, the cox17-RNAi mutant showed no
      modification of respiration and of H(2)O(2) production in the dark but a two to
      threefold increase of H(2)O(2) in the light compared to wild type and the cox3
      RNAi mutant. The cox17-RNAi mutant was more sensitive to cadmium than the wild
      type and cox3-RNAi strains. This suggested that besides its role in complex IV
      assembly, Cox17 could have additional functions in the cell such as metal
      detoxification or Reactive Oxygen Species protection or signaling. Concerning
      Cox3, its role in Chlamydomonas complex IV is similar to that of other eukaryotes
      although this subunit is encoded in the nuclear genome in the alga contrary to
      the situation found in all other organisms.

PMID- 20700629
TI  - Nuclear copies of mitochondrial genes: another problem for ancient DNA.
AB  - The application of ancient DNA techniques is subject to many problems caused
      primarily by low quality and by low quantity of DNA. For these reasons most
      studies employing ancient DNA rely on the characterization of mitochondrial DNA,
      which is present in many more copies per cell than nuclear DNA and hence more
      copies are likely to survive. We used universal and taxon specific mitochondrial
      primers to amplify DNA from museum specimens, and found many instances where the
      amplification of nuclear copies of the mitochondrial gene (numts) instead of the
      targeted mitochondrial fragment had occurred. Furthermore, the likelihood of
      amplifying numts increased dramatically when universal primers were utilized.
      Here we suggest that ancient DNA practitioners must consider the possibility that
      numts can be amplified at higher rates than previously thought. This is another
      complication for ancient DNA studies, but it also suggests that more extensive
      inclusion of nuclear markers in ancient DNA studies should be feasible.

PMID- 20700631
TI  - Multifunctional tumor-targeted polymer-peptide-drug delivery system for treatment
      of primary and metastatic cancers.
AB  - PURPOSE: In order to improve drug delivery to drug-resistant ovarian tumors, we
      constructed a multifunctional polymer-peptide-drug conjugate (PPDC) system for
      effective treatment of primary and metastatic ovarian cancers. METHODS: The PPDC
      consists of the poly(Ethylene Glycol) (PEG) polymeric carrier conjugated via
      citric acid spacers to anticancer drug (Camptothecin, CPT), tumor targeting
      moiety (LRHR, a synthetic analog of luteinizing hormone-releasing hormone) and a
      suppressor of cellular antiapoptotic defense (BH3 peptide). To test the
      conjugates in vitro and in vivo, cancer cells were isolated from tissue samples
      obtained from patients with ovarian primary tumor and metastatic malignant
      ascites. RESULTS: It was found that cells isolated from malignant ascites were
      more aggressive in terms of tumor growth and more resistant to chemotherapy when
      compared with those isolated from primary tumors. PPDC containing two copies of
      drugs and peptides was most efficient in treatment of primary tumors and
      intraperitoneal metastases. Multiple treatments with this PPDC led to almost
      complete regression of primary tumor and prevented growth of malignant ascites.
      CONCLUSION: The proposed multifunctional polymeric delivery system which consists
      of multiple copies of the drug and peptides demonstrated significantly higher
      antitumor activity in primary and metastatic cancers when compared with drug
      alone and PEG-CPT conjugate.

PMID- 20700632
TI  - Mixed pH-sensitive polymeric micelles for combination drug delivery.
AB  - PURPOSE: To prepare mixed polymeric micelles that can carry two different drugs,
      doxorubicin (DOX) and 17-hydroxyethylamino-17-demethoxygeldanamycin (GDM-OH), for
      combination cancer chemotherapy. METHODS: The pH-sensitive micelles were prepared
      from poly(ethylene glycol)-poly(aspartate hydrazide) block copolymers to which
      either DOX or GDM-OH is conjugated through acid-labile hydrazone bond (individual
      micelles). Mixed micelles were formed not only by simply mixing two different
      individual micelles in aqueous solutions (aqueous mixed micelles) but also by
      evaporating organic solvents from the organic/aqueous mixed solvents in which two
      block copolymers possessing different drugs were dissolved homogeneously (organic
      mixed micelles). Particle size measurements, pH-dependent drug release tests,
      cytotoxicity assays and western blot analysis were subsequently conducted.
      RESULTS: Individual and aqueous/organic mixed micelles showed clinically relevant
      particle size (<100 nm) and pH-dependent drug release patterns. Mixed polymer
      micelles suppress cancer cell growth effectively in a drug concentration, mixing
      method and schedule-dependent way. CONCLUSION: Combination chemotherapy using
      polymeric micelles seems to minimize a schedule-dependent change in combination
      drug efficacy in comparison to drug combination using DMSO formulations.

PMID- 20700633
TI  - Protective effects of crude garlic by reducing iron-mediated oxidative stress,
      proliferation and autophagy in rats.
AB  - The impact of garlic, known for its antioxidant activities, on iron metabolism
      has been poorly investigated. The aim of this work was to study the effect of
      crude garlic pre-treatment on iron-mediated lipid peroxidation, proliferation and
      autophagy for 5 weeks. Rats were fed distilled water or garlic solution (1 g/kg
      body weight) by gavage for the first 3 weeks as pre-treatment and received a
      basal diet supplemented or not with ferrous sulfate (650 mg Fe/kg diet) for the
      last 2 weeks of treatment. Immunohistochemistry labeling and ultrastuctural
      observations were used to evaluate the iron deleterious effects in the liver.
      Iron supplementation induced cell proliferation predominantly in non parenchymal
      cells comparing to hepatocytes, but not apoptosis. In addition, iron was
      accumulated within the hepatic lysosomes where it triggers autophagy as evidenced
      by the formation of autophagic vesicles detected by LC3-II staining. It also
      induced morphologic alterations of the mitochondrial membranes due to increased
      lipid peroxidation as shown by elevated iron and malondialdehyde concentrations
      in serum and tissues. Garlic pre-treatment reduced iron-catalyzed lipid
      peroxidation by decreasing the malondialdehyde level in the liver and colon and
      by enhancing the status of antioxidants. In addition, garlic reduced the iron
      mediated cell proliferation and autophagy by lowering iron storage in the liver
      and protected mitochondrial membrane. Based on these results, garlic treatment
      significantly prevented iron-induced oxidative stress, proliferation and
      autophagy at both biochemical and histological levels due to its potent free
      radical scavenging and antioxidant properties.

PMID- 20700634
TI  - Association between hepatitis B viral burden in chronic infection and a
      functional single nucleotide polymorphism of the PDCD1 gene.
AB  - BACKGROUND: PD-1, encoded by PDCD1, is highly expressed on virus-specific T cells
      and plays critical roles in modulating anti-virus immune responses in chronic
      viral infection. It is unknown, however, whether polymorphisms of the PDCD1 are
      associated with viral clearance during chronic viral infections. METHODOLOGY AND
      PRINCIPAL FINDINGS: Here, we used the polymerase chain reaction-restriction
      fragment length polymorphism method to genotype two single nucleotide
      polymorphisms (SNPs) of PDCD1 in 502 patients with chronic hepatitis B virus
      (HBV) infection and 359 healthy controls to determine the association between
      PDCD1 genotypes and serum viral load as well as the risk of chronic infection.
      Our results showed that although neither the P7209(C/T) SNP site nor the
      P8737(A/G) site was associated with the risk of chronic HBV infection, the P7209
      (T) allele in intron 4 is significantly associated with lower viral burden in the
      blood. Using a luciferase reporter assay, we demonstrated that the P7209 (T)
      allele creates a negative cis-element for gene transcription. CONCLUSIONS AND
      SIGNIFICANCE: Our data provide the first evidence that PDCD1 polymorphisms is a
      genetic factor in pathogenesis of chronic viral infection and reveal the
      functional significance of the P7209 SNP of the PDCD1.

PMID- 20700635
TI  - Expanding roles: a survey of public health genetic counselors.
AB  - According to the 2008 National Society of Genetic Counselors (NSGC) Professional
      Status Survey (PSS), 31 genetic counselor respondents reported spending at least
      50% of their time in the area of public health. The NSGC Public Health Special
      Interest Group (PHSIG) had 49 dues-paying members in 2009. The purpose of this
      study was to identify the work settings and public health activities in which
      genetic counselors participate. A novel online survey was disseminated over the
      NSGC PHSIG Listserv. Forty-one percent (n = 13) of public health genetic
      counselor respondents worked in a university medical system, while 53% (n = 17)
      were grant-funded and held a non-clinical appointment. The most common public
      health activities included educating healthcare professionals (82%) and community
      members (61%), research (55%), grant writing (55%) and grant administration
      (36%). Most respondents (82%) reported learning certain public health skills
      outside of their genetic counseling training programs. Differences in work
      settings were found, with a significantly greater percentage of public health
      genetic counselors working in government agencies. Genetic counselors have
      opportunities to become involved in public health activities as the scope of
      public health genetics grows. Furthermore, genetic counseling competencies are
      compatible with the Institute of Medicine's "10 Essential Public Health
      Services." The NSGC and genetic counseling training programs are encouraged to
      offer more public health learning opportunities for genetic counselors and
      genetic counseling students interested in this specialty area.

PMID- 20700636
TI  - Immigration status, acculturation, and dating violence risk for Hispanic
      adolescent girls in New Mexico.
AB  - Little data exist on dating violence experienced by immigrant Hispanic
      adolescents. The present study examined the relationships between immigration
      status, language spoken at home, and dating violence experienced by Hispanic
      adolescent girls in New Mexico. Data from the 2007 New Mexico Youth Risk and
      Resiliency Surveys were analyzed. Adjusted logistic regression analyses were
      conducted among the full sample of Hispanic females (N = 3,412) and among strata
      based on immigration status. Immigrant Hispanic girls were as likely as non
      immigrant Hispanic girls to have experienced dating violence in the prior year (P
      = 0.93). Among immigrant Hispanic girls, those who were Non-English-dominant were
      one-fourth as likely to have experienced dating violence as those immigrant girls
      who were English-dominant (aOR 0.27 [95% CI 0.08-0.87]). Among US-born Hispanic
      girls, those who were Non-English-dominant were less likely to have experienced
      dating violence; however, this value did not reach statistical significance (aOR
      0.65 [95% CI 0.33-1.27]). Past sexual experience was a significant risk factor
      for dating violence for US-born Hispanic girls (aOR 4.99 [95% CI 3.18-7.83]) but
      not for immigrant Hispanic girls (aOR 1.66 [95% CI 0.63-4.43]). Immigrant status
      was not found to be protective against dating violence for New Mexico Hispanic
      girls. However, those immigrant girls who were less acculturated in terms of
      language used at home were found to have only a quarter of the risk of dating
      violence as those more acculturated. The use of heritage language by immigrant
      Hispanic girls may be a protective factor against dating violence. Further
      studies are indicated to confirm this finding.

PMID- 20700637
TI  - Synaptic and intrinsic determinants of the phase resetting curve for weak
      coupling.
AB  - A phase resetting curve (PRC) keeps track of the extent to which a perturbation
      at a given phase advances or delays the next spike, and can be used to predict
      phase locking in networks of oscillators. The PRC can be estimated by convolving
      the waveform of the perturbation with the infinitesimal PRC (iPRC) under the
      assumption of weak coupling. The iPRC is often defined with respect to an
      infinitesimal current as z(i)(phi), where phi is phase, but can also be defined
      with respect to an infinitesimal conductance change as z(g)(phi). In this paper,
      we first show that the two approaches are equivalent. Coupling waveforms
      corresponding to synapses with different time courses sample z(g)(phi) in
      predictably different ways. We show that for oscillators with Type I
      excitability, an anomalous region in z(g)(phi) with opposite sign to that seen
      otherwise is often observed during an action potential. If the duration of the
      synaptic perturbation is such that it effectively samples this region, PRCs with
      both advances and delays can be observed despite Type I excitability. We also
      show that changing the duration of a perturbation so that it preferentially
      samples regions of stable or unstable slopes in z(g)(phi) can stabilize or
      destabilize synchrony in a network with the corresponding dynamics.

PMID- 20700638
TI  - Maternal early life factors associated with hormone levels and the risk of having
      a child with an autism spectrum disorder in the nurses health study II.
AB  - It is not known whether reproductive factors early in the mother's life influence
      risk of autism spectrum disorders (ASD). We assessed maternal age at menarche,
      menstrual cycle characteristics during adolescence, oral contraceptive use prior
      to first birth, body shape, and body mass index (BMI) in association with ASD
      using binomial regression in a cohort study of 61,596 women, including 743 cases.
      Overall, early life factors were not associated with ASD, though early age at
      menarche (RR for age 10 or less = 1.54, 95% CI 1.18, 2.02, p = 0.0002) and BMI at
      age 18 of >=30 (RR 2.03, 95% CI 1.34, 3.08, p = 0.0008) were significantly
      associated with increased risk of ASD. Further work should investigate the
      potential influence of these factors.

PMID- 20700639
TI  - Interpretation of ambiguous situations: evidence for a dissociation between
      social and physical threat in williams syndrome.
AB  - Williams syndrome (WS) is associated with an unusual profile of anxiety,
      characterised by increased rates of non-social anxiety but not social anxiety
      (Dodd and Porter, J Ment Health Res Intellect Disabil 2(2):89-109, 2009). The
      present research examines whether this profile of anxiety is associated with an
      interpretation bias for ambiguous physical, but not social, situations. Sixteen
      participants with WS, aged 13-34 years, and two groups of typically developing
      controls matched to the WS group on chronological age (CA) and mental age (MA),
      participated. Consistent with the profile of anxiety reported in WS, the WS group
      were significantly more likely to interpret an ambiguous physical situation as
      threatening than both control groups. However, no between-group differences were
      found on the ambiguous social situations.

PMID- 20700641
TI  - New method to measure and improve consistency of baroreflex sensitivity values.
AB  - OBJECTIVE: Baroreflex sensitivity (BRS) is an important prognostic index in
      cardiovascular diseases, however, its use is complicated by different methods
      difficult to compare and standardize, often providing conflicting results. We
      tested whether the simple ratio of RR interval to systolic blood pressure global
      variabilities (assessed by standard deviations) is a reliable measure of BRS, by
      measuring the agreement with six established methods. In addition, we tested
      whether high-pass filtering of data, by removing slow non-baroreflex-mediated
      fluctuations, could improve the agreement between different BRS methods. METHODS:
      In 1,409 subjects, we compared 6 established methods (derived by cross-spectral
      and sequence analysis) and the new method, supine and in response to tilting
      (1,175 subjects). Data were analyzed after linear detrending, high-pass filtering
      at 0.025 and 0.05 Hz. RESULTS: Although all seven methods showed a general
      agreement, the new method consistently showed the lowest distance from the median
      of the remaining methods (0.04 +/- 0.06 ms/mmHg over 2,584 files, p < 0.05 with
      respect to the second best method). High-pass filtering improved (p < 0.001) the
      agreement between methods without reducing the sensitivity to changes induced by
      tilting. Only the new method could provide estimates in all 2,584 files tested.
      INTERPRETATION: The new method intercepts the mean information of all other
      methods better than any other method, hence providing a simple, easy to
      standardize (no mathematical constraints) and yet robust and reliable BRS
      estimate. High-pass filtering markedly improves the agreement of all methods,
      without loss of sensitivity, and could be routinely used in clinical trials, to
      provide comparable BRS estimates.

PMID- 20700640
TI  - Autonomic function following endoscopic thoracic sympathotomy for hyperhidrosis.
AB  - PURPOSE: Primary palmar-plantar hyperhidrosis is the condition of excessive
      sweating of the hands and feet. For severe and medically refractory cases,
      endoscopic thoracic sympathotomy (ETS) is a bilateral ganglion-sparing
      disconnection between the stellate and T2 ganglion in an effort to minimize
      compensatory hyperhidrosis. The purpose of this study was to determine the effect
      of ETS on cardiac autonomic function. METHODS: Participants in this study were 22
      otherwise healthy hyperhidrosis patients with 17 returning 1-12 months after
      surgery. Heart rate (HR) and blood pressure were collected at rest and during
      sequential nitroprusside/phenylephrine infusion (modified Oxford). To determine
      change in cardiac autonomic function, heart rate variability indices of RMSSD, LF
      and HF (log, nu) power were calculated. Sequential baroreflex sensitivity was
      also calculated. RESULTS: After surgery, resting HR on standardized ECG tended to
      be lower and reached significance during the modified Oxford baseline (p <
      0.001). HRV changed significantly between assessments with an increase in HF (nu)
      and decrease in LF (nu) and LF (log) spectral ranges (p < 0.05), while the
      increase in RMSSD was marginally significant (p < 0.06). Compared with matched
      controls, HRV indices were significantly different before surgery, but similar
      after surgery. No change was detected in resting sequential baroreflex
      sensitivity, baroslope obtained by modified Oxford or QTc interval. CONCLUSIONS:
      We conclude that ETS changes cardiac autonomic modulation of HR to levels similar
      to controls. Despite the minimally destructive nature of ETS, effects on HRV are
      consistent with previously reported post-sympathectomy blunting of exaggerated
      sympathetic control associated with hyperhidrosis. No significant changes in the
      baroreflex indices suggest that ETS did not significantly affect blood pressure
      regulation.

PMID- 20700642
TI  - Hemodynamics following endoscopic thoracic sympathotomy for palmar hyperhidrosis.
AB  - PURPOSE: We studied patients with palmar hyperhidrosis before and after
      endoscopic thoracic sympathotomy (ETS) to determine the effect of chronic
      sympathetic denervation on (1) forearm blood flow (FBF) response to mental stress
      and (2) exercise tolerance. METHODS AND RESULTS: Twenty-two healthy patients were
      evaluated before ETS, and 17 returned after surgery (11 F; 19-32 years). We
      measured heart rate (HR; 12 lead), blood pressure, and FBF (plethysmography, ml
      dl(-1) min(-1)). Supine HR tended to decrease after ETS (69 +/- 10 vs. 66 +/- 6,
      p = 0.2). Mental stress FBF was recorded during baseline, 3-min Stroop color word
      test, and 2-min recovery. Mental stress responses were unaffected by ETS.
      However, during post-mental stress recovery period, ETS resulted in a significant
      elevation in FBF (2 +/- 1 vs. 3 +/- 1), FVC (3 +/- 1 vs. 4 +/- 2), and a decrease
      in FVR (52 +/- 22 vs. 32 +/- 16, p < 0.01 for all). ETS resulted in a reduction
      in pre-exercise seated baseline HR (94 +/- 2.5 beats/min preoperatively vs. 84 +/
      4.3 beats/min postoperatively, p < 0.05), maximal HR response to cycle exercise,
      and exercise systolic blood pressure (172 +/- 5.2 mmHg pre-op vs. 158 +/- 5.9
      mmHg post-op, p < 0.05) but not mean or diastolic pressure. VO(2)max and exercise
      duration determined by cycle ergometry was unchanged. CONCLUSIONS: Functional
      evidence of upper limb denervation is observed during the FBF recovery period
      from mental stress and hemodynamic alterations associated with upright cycle
      exercise. However, the sustained exercise capacity suggests modest clinical
      consequences.

PMID- 20700644
TI  - Using mobile phones to improve clinic attendance amongst an antiretroviral
      treatment cohort in rural Uganda: a cross-sectional and prospective study.
AB  - We aimed to assess the patterns and dynamics of mobile phone usage amongst an
      antiretroviral treatment (ART) cohort in rural Uganda and ascertain its
      feasibility for improving clinic attendance. A cross-sectional study of clients
      on ART exploring their access to mobile phones and patterns of use was employed.
      Clinic attendances for antiretroviral drug refills were then monitored
      prospectively over 28 weeks in 176 patients identified in the cross-sectional
      survey who had access to mobile phones and had given consent to be contacted.
      Patients were contacted via voice calls or text messages to remind them about
      their missed clinic appointments. Of the 276 patients surveyed, 177 (64%) had
      access to mobile phones with all but one were willing to be contacted for missed
      visits reminders. Of the 560 total scheduled clinic appointments, 62 (11%) were
      missed visits. In 79% of episodes in which visits were missed, patients presented
      for treatment within a mean duration of 2.2 days (SD = 1.2 days) after mobile
      phone recall. Access to mobile phones was high in this setting. Privacy and
      confidentiality issues were not considered deterrents. Mobile phones have a
      potential for use in resource-constrained settings to substantially improve the
      clinical management of HIV/AIDS.

PMID- 20700643
TI  - Heritability of delay discounting in adolescence: a longitudinal twin study.
AB  - Delay discounting (DD) refers to the preference for smaller immediate rewards
      over larger but delayed rewards, and is considered to be a distinct component of
      a broader "impulsivity" construct. Although greater propensity for discounting
      the value of delayed gratification has been associated with a range of problem
      behaviors and substance abuse, particularly in adolescents, the origins of
      individual differences in DD remain unclear. We examined genetic and
      environmental influences on a real-life behavioral measure of DD using a
      longitudinal twin design. Adolescent participants were asked to choose between a
      smaller ($7) reward available immediately and a larger ($10) reward to be
      received in 7 days. Biometrical genetic analysis using linear structural equation
      modeling showed significant heritability of DD at ages 12 and 14 (30 and 51%,
      respectively) and suggested that the same genetic factors influenced the trait at
      both ages. DD was significantly associated with symptoms of conduct disorder,
      attention deficit hyperactivity disorder, substance use, and with higher novelty
      seeking and poor self-regulation. This study provides the first evidence for
      heritability of DD in humans and suggests that DD can be a promising
      endophenotype for genetic studies of addiction and externalizing disorders.

PMID- 20700645
TI  - HIV disclosure, condom use, and awareness of HIV infection among HIV-positive,
      heterosexual drug injectors in St. Petersburg, Russian Federation.
AB  - We examined the prevalence of HIV disclosure to sexual partners by HIV-positive
      drug injectors (IDUs) in St. Petersburg, Russia and compared the magnitude and
      direction of associations of condom use with awareness of one's HIV infection and
      disclosure to partners. Among 157 HIV-infected participants, awareness of
      infection at time of last intercourse was associated with condom use with
      partners perceived to be HIV-negative (aOR 6.68, 95% CI 1.60-27.88). Among the 70
      participants aware of their infection prior to enrolment, disclosure to
      potentially uninfected sexual partners was independently and negatively
      associated with condom use (aOR 0.13, 95% CI 0.02-0.66). Disclosure was
      independently associated with having injected >= 9 years (aOR 6.04, 95% CI 1.53
      23.77) and partnership with another IDU (aOR 3.61, 95% CI 1.44-9.06) or HIV
      seropositive (aOR 45.12, 95% CI 2.79-730.46). Scaling up HIV testing services and
      interventions that increase the likelihood of individuals receiving their test
      results is recommended.

PMID- 20700646
TI  - Loneliness, depressive symptomatology, and suicide ideation in adolescence: cross
      sectional and longitudinal analyses.
AB  - The paper presents the first known longitudinal study of the relationship between
      loneliness, depressive symptoms, and suicide ideation in adolescence, in a
      stratified sample of high school students (Time 1 N = 1009; 57 % female; Time 2 N
      = 541; 60 % female). Cross-lagged structural equation modeling indicated that
      depressive symptoms led to more loneliness across time, whereas loneliness did
      not predict higher levels of depressive symptoms across time. Loneliness was
      found to be a correlate of depressive symptoms at the cross-sectional level,
      independent of gender, other demographic factors, multiple psychosocial
      variables, and social desirability. Loneliness did not predict suicide ideation
      over time or at the cross-sectional level, when controlling for depressive
      symptoms. Gender did not predict loneliness, depressive symptoms or suicide
      ideation across time. Future longitudinal studies of the relationship between
      loneliness, depressive symptoms, and suicide ideation in adolescence should use
      more extensive designs.

PMID- 20700647
TI  - Disseminated tumor cells: the method is the message.

PMID- 20700649
TI  - Lead (Pb) and arsenic (As) bioaccessibility in various soils from south China.
AB  - Seventeen soil samples with various concentrations of lead (Pb) and arsenic (As)
      were collected from five provinces of south China, and bioaccessibility of Pb and
      As in the soils were examined using a physiologically based extraction test. The
      results showed that the bioaccessibility ranged from 24.6% to 82.5% and 2.3% to
      57.5% for Pb, 2.5% to 65.5% and 1.2% to 31.8% for As in the gastric and small
      intestinal phases, respectively. The effect of soil properties on the
      bioaccessible of Pb/As was evaluated. Path analysis showed that coefficients of
      determination (R (2)) for the bioaccessible Pb were 0.93 in the both gastric and
      small intestinal phases and for the bioaccessible As were 0.98 and 0.99 in the
      gastric and small intestinal phases, respectively. Among all the soil
      characteristics, OM, DCBFe, CEC, and WAs were significant for controlling PbD,
      and CEC, CaCl(2)-Pb, and WAs were important for controlling PbI. Partitioning by
      path analysis also showed significant direct effects by CaCl(2)-Pb and WAs on
      AsD, and OM, CEC, CaCl(2)-Pb, and WAs on AsI.

PMID- 20700648
TI  - Diagnosis of second breast cancer events after initial diagnosis of early stage
      breast cancer.
AB  - To examine whether there are any characteristics of women or their initial tumors
      that might be useful for tailoring surveillance recommendations to optimize
      outcomes. We followed 17,286 women for up to 5 years after an initial diagnosis
      of ductal carcinoma in situ (DCIS) or early stage (I/II) invasive breast cancer
      diagnosed between 1996 and 2006. We calculated rates per 1,000 women years of
      recurrences and second breast primaries relative to demographics, risk factors,
      and characteristics of initial diagnosis: stage, treatment, mode of initial
      diagnosis. Nearly 4% had a second breast cancer event (314 recurrences and 344
      second breast primaries). Women who used adjuvant hormonal therapy or were >= 80
      years had the lowest rates of second events. Factors associated with higher
      recurrence and second primary rates included: initial DCIS or stage IIB,
      estrogen/progesterone receptor-negative, younger women (<50 years). Women with a
      family history or greater breast density had higher second primary rates, and
      women who received breast conserving surgery without radiation had higher
      recurrence rates. Roughly one-third of recurrences (37.6%) and second primaries
      (36.3%) were not screen-detected. Initial mode of diagnosis was a predictor of
      second events after adjusting for age, stage, primary treatment, and breast
      density. A recent negative mammogram should not falsely reassure physicians or
      women with new breast symptoms or changes because one-third of second cancers
      were interval cancers. This study does not provide any evidence in support of
      changing surveillance intervals for different subgroups.

PMID- 20700650
TI  - Distribution and solid-phase speciation of toxic heavy metals of bed sediments of
      Bharali tributary of Brahmaputra River.
AB  - Heavy metal (Fe, Mn, Zn, Cu, Ni, Pb, and Cd) concentrations and their chemical
      speciations were investigated for the first time in bed sediments of Bharali
      River, a major tributary of the Brahmaputra River of the Eastern Himalayas.
      Levels of Fe, Mn, Pb, and Cd in the bed sediments were much below the average
      Indian rivers; however, Cu and Zn exhibit levels on the higher side. Enrichment
      factors (EF) of all metals was greater than 1 and a higher trend of EF was seen
      in the abandoned channel for most metals. Pb showed maximum EF of 32 at site near
      an urban center. The geoaccumulation indices indicate that Bharali river is
      moderately polluted. The metals speciations, done by a sequential extraction
      regime, show that Cd, Cu, and Pb exhibit considerable presence in the
      exchangeable and carbonate fraction, thereby showing higher mobility and
      bioavailability. On the other hand, Ni, Mn, and Fe exhibit greater presence in
      the residual fraction and Zn was dominant in the Fe-Mn oxide phase. Inter-species
      correlations at three sites did not show similar trends for metal pairs
      indicating potential variations in the contributing sources.

PMID- 20700651
TI  - Imposex and butyltin concentrations in Bolinus brandaris (Gastropoda: Muricidae)
      from the northern Tunisian coast.
AB  - The imposex incidence and butyltin concentration i.e. tributyltin with its di-
      and mono-substituted metabolites were investigated in the muricid Bolinus
      brandaris sampled from two sites on the northern Tunisian coast (the Lagoon of
      Bizerta and the small Gulf of Tunis). Both populations had imposex, with stages
      of imposex development varying between VDS 1 and VDS 4.3. All imposex indices
      (imposex frequency (I %), female penis length, female vas deferens length, vas
      deferens sequence index, relative penis length index, and vas deferens length
      index) were significantly higher in snails from the Bizerta lagoon. Butyltins
      were detected in the whole tissues of both sexes from the two sites. TBT levels
      were higher in gastropods collected from the lagoon of Bizerta (12.65 +/-1.48 ng
      Sn g( - 1) dw in female and 15.21 +/-1.13 ng Sn g( - 1) dw in male) than in
      individuals from the Gulf of Tunis (10.71 +/-1.26 ng Sn g( - 1) dw in female and
      11.65 +/-1.63 ng Sn g( - 1) dw in male), corroborating the data of imposex
      analysis. These results confirmed that B. brandaris could be used as a
      bioindicator species of butyltin pollution in the studied areas. In addition,
      this study provided baseline data that could serve for long-term monitoring of
      TBT pollution in Tunisia, since legislation to reduce the use of TBT-based
      antifouling paints has not been introduced yet.

PMID- 20700652
TI  - Long-term variations of water quality parameters in the Maroon River, Iran.
AB  - Sixteen water quality parameters have been monitored at four stations located
      along the Maroon River during 1989-2008. The trend analysis was performed on
      seasonal and annual time-scales using the Mann-Kendall test, the Sen's slope
      estimator and the linear regression. The relationships of the water quality
      parameters to river discharge were also investigated. The statistical methods
      showed both positive and negative trends in annual water quality data. However,
      significant trends were detected by the statistical methods only in calcium,
      magnesium, sodium absorption ratio, pH, and turbidity series. The results
      indicated that the concentrations of the water quality parameters increased in
      spring and winter seasons, while the concentrations were diluted in summer and
      autumn seasons in the last two decades. Moreover, the highest numbers of
      significant trends were found in the spring and summer series, respectively.
      According to the regression analysis, most of the water quality parameters were
      negatively correlated with river discharge.

PMID- 20700653
TI  - Recent advances in nanotechnology based drug delivery to the brain.
AB  - Drug delivery into the brain was difficult due to the existence of blood brain
      barrier, which only permits some molecules to pass through freely. In past
      decades, nanotechnology has enabled many technical advances including drug
      delivery into the brain with high efficiency and accuracy. In the present paper,
      we summarize recent important advances in employing nanotechnology for drug
      delivery to the brain as well as controlled drug release.

PMID- 20700654
TI  - A cohort study investigating patient expectations and satisfaction outcomes in
      men undergoing robotic assisted radical prostatectomy.
AB  - INTRODUCTION: Robotic assisted radical prostatectomy (RARP) is gaining widespread
      acceptance for the management of localized prostate cancer. However, data
      regarding patient expectations and satisfaction outcomes after RARP are scarce.
      METHODS: We developed a structured program for preoperative education and
      evidence-based counseling using a multi-disciplinary team approach and measured
      its impact on patient satisfaction in a cohort of 377 consecutive patients who
      underwent RARP at our institution. Responses regarding overall, sexual, and
      continence satisfaction were assessed. RESULTS: Fifty percent of our patient
      cohort replied to the questionnaire assessments. Ninety-three percent of
      responding patients expressed overall satisfaction after RARP with only 0.5%
      expressing regret at having had the operation. Biochemical recurrence and lack of
      continence correlated significantly with low levels of satisfaction, though
      sexual function was not significantly different among those satisfied and those
      not. Most patients (97%) valued oncologic outcome as their top priority, with
      regaining of urinary control being the commonest second priority (60%).
      CONCLUSIONS: RARP appears to be associated with a high degree of patient
      satisfaction in a cohort of patients subjected to a structured preoperative
      education and counseling program. Oncologic outcomes are most important to these
      patients and have the largest influence on satisfaction scores.

PMID- 20700655
TI  - Impact of plaque haemorrhage and its age on structural stresses in
      atherosclerotic plaques of patients with carotid artery disease: an MR imaging
      based finite element simulation study.
AB  - Plaque haemorrhage (PH) in atherosclerotic plaques is associated with recurrent
      thromboembolic ischaemic events. The healing process predominantly involves the
      repair of the plaque rupture site and the replacement of fresh PH with chronic
      PH, which is either reabsorbed or replaced by fibrous tissue. The extent to which
      the presence of PH, and its type i.e. fresh or chronic, affects plaque stability
      remains unexplored. Finite element analysis (FEA)-based biomechanical stress
      simulations can provide quantification of the percentage contribution of PH and
      its types to the biomechanical stresses of plaques, thereby providing information
      about its role in plaque stability. Fifty-two patients with atherosclerotic
      carotid disease underwent high resolution magnetic resonance (MR) imaging of
      their carotid arteries in a 1.5 Tesla MR system. Twenty-three patients had MR
      identifiable PH and were selected. Only those images of these patients were used
      for simulations, which had evidence of PH. Manual segmentation of plaque
      components, such as lipid pool, fibrous tissue, calcium and PH, was done using
      carotid MR images. Plaque components and vessel wall were modelled as isotropic,
      incompressible hyperelastic materials with non-linear properties undergoing
      deformation under patient-specific blood pressure loading. Two dimensional
      structure-only FEA was used for quantification of maximum critical stress (M
      CStress) of plaques. The median M-CStress of symptomatic patients with fresh PH
      was 159 kPa (IQR: 114-253). Because PH usually occurs within the lipid pool, when
      the simulation was repeated with lipid pool replacing fresh PH to simulate the
      pre-rupture plaque state, M-CStress was reduced by 26% [118 kPa (IQR: 79-189)
      (P=0.001)]. When fresh PH was replaced with chronic PH it resulted in a 30%
      reduction in the M-CStress [118 kP (IQR: 79-189), (P=0.001)]. PH affects stresses
      within atheroma to various degrees depending on its type, thereby influencing
      plaque stability to a different extent, with fresh PH significantly increasing
      the biomechanical stresses. Plaque component-dependent stress analysis has the
      potential of identifying the critical nature of various plaque components.

PMID- 20700656
TI  - Versatile methods for the fabrication of polyvinylidene fluoride microstructures.
AB  - Polyvinylidene fluoride (PVDF) microstructures are of interest for a number of
      BioMEMS applications both for their piezoelectric and biocompatible properties.
      In this work, simple soft lithography-based techniques were developed to
      fabricate PVDF microstructures with diverse geometries, including microarrays of
      pillars, lines, and wells. Four different microstructure configurations were
      created: freestanding, stamped discontinuous, stamped continuous and imprinted
      patterns. Features with lateral dimensions down to 1 MUm were consistently
      reproduced on 2.5 cm diameter areas. Atomic force microscopy (AFM) measurements
      of poled PVDF microstructures confirmed a marked inverse piezoelectric behavior.
      The techniques presented here have a number of advantages over previously
      demonstrated PVDF micropatterning approaches.

PMID- 20700657
TI  - Impact and characteristics of quality of life in Japanese patients with multiple
      sclerosis.
AB  - PURPOSE: To evaluate health-related quality of life (HRQOL) in Japanese patients
      with multiple sclerosis (MS) and investigate associations between the results of
      these QOL assessments and disease severity. METHODS: One-hundred sixty-three
      Japanese MS patients completed a questionnaire battery comprising the Functional
      Assessment of MS (FAMS), the Nottingham Adjustment Scale-Japanese version (NAS
      J), and the European QOL scale (EQ-5D). Additional five factors affecting QOL as
      identified by MS patients in a focus group interview were also investigated:
      employment status, change of income, availability of disease information,
      communication with medical staff, and care received. Disease severity was
      determined using the Expanded Disability Status Scale (EDSS). RESULTS: There was
      a strong negative correlation of the subscale scores for mobility, symptoms,
      emotional well-being, thinking and fatigue, and additional concerns on the FAMS
      with EDSS score. For the NAS-J, only acceptance of the condition was correlated
      with disease severity. Among the five additional aspects of the condition
      identified by patients, employment status, income, and disease information were
      shown to be important for maintaining QOL in patients with MS. CONCLUSIONS:
      Support for finding employment and having increased or maintained household
      income and readily available information about the disease contribute to
      improving QOL in Japanese MS patients.

PMID- 20700658
TI  - Age-related deregulation of naive T cell homeostasis in elderly humans.
AB  - Immunosenescence is characterized by phenotypic and functional changes of
      effector memory T cells. In spite of the well-described senescent defects of
      these experienced T cells, immune responses to new pathogens are also deeply
      affected in elderly humans, suggesting that naive T cells could also show age
      related defects. It has been reported in both, animal models and humans,
      alterations of the naive T cell turnover associated to advanced age or low thymic
      function. However, as far as we know, homeostatic mechanisms involved in the
      deregulation of naive T cell peripheral dynamics and their consequences are still
      not well understood. Thus, the aim of our study was to analyze homeostatic
      parameters of peripheral naive T cells and their relationship with thymic
      function in young and elderly humans. Our results show that lower naive T cell
      numbers were associated with a lower thymic function and higher activation and
      proliferating naive T cell levels. We then analyzed sjTREC numbers and relative
      telomere length from sorted naive T cells. Our results show that the aberrant
      activation and proliferation status was related to lower sjTREC numbers (a
      peripheral proliferation marker) and both, higher CD57 expression levels and
      shortened telomeres (replicative senescence-related markers). Elderly individuals
      show a greater contraction of the CD8 naive T cell numbers and all homeostatic
      alterations were more severe in this compartment. In addition, we found that low
      functional thymus show a CD4-biased thymocyte production. Taken together, our
      results suggest a homeostatic deregulation, affecting mostly the naive CD8 T cell
      subset, leading to the accumulation of age-associated defects in, otherwise,
      phenotypically naive T cells.

PMID- 20700659
TI  - Ecological risk of long-term chlorimuron-ethyl application to soil microbial
      community: an in situ investigation in a continuously cropped soybean field in
      Northeast China.
AB  - INTRODUCTION: Chlorimuron-ethyl has been widely used for the soybean production
      of China, but less information is available on the possible risk of long-term
      application of this herbicide. MATERIALS AND METHODS: In this paper, soil samples
      were collected from the plots having been received 30 g active component of
      chlorimuron-ethyl/ha per year for 5 and 10 years in a continuously cropped
      soybean field of Northeast China, with their microbial community analyzed by
      plate counting, PCR-DGGE, and cloning library. Chlorimuron-ethyl had a higher
      accumulation in test soils, and the accumulation decreased the CFU of soil
      bacteria and increased the CFU of soil fungi significantly. The CFU of soil
      actinomycetes only had a significant decrease in the plot having been received
      chlorimuron-ethyl for 10 years. RESULTS AND DISCUSSION: Under the long-term
      stress of chlorimuron-ethyl, the diversity and evenness of soil microbial
      community decreased, and more importantly, some bacterial and fungal species that
      possibly benefited soybean's growth, e.g., Acidobacteria, gamma-proteobacteria,
      Cortinarius violaceu, Acarospora smaragdula, and Xerocomus chrysenteron decreased
      or demised, while some species that could induce the obstacle of soybean's
      continuous cropping, e.g., Fusarium oxysporum, Rhizoctonia solani, and
      Phytophthora sojae, increased or appeared. Some actinomycetes were inhibited
      having negative effects on the antagonism between soil microbes. It is considered
      that due to the longer half-life of chlorimuron-ethyl in soil and the resistance
      and resilience of soil microbes to short-term environmental stress, long-term in
      situ investigation rather than laboratory microcosm test or short-term field
      experiment would be more appropriate to the accurate assessment of the ecological
      risk of long-term chlorimuron-ethyl application. Further studies should be made
      on the application mode and duration of chlorimuron-ethyl to reduce the possible
      ecological risk of applying this herbicide on continuously cropped soybean field.

PMID- 20700660
TI  - Patterns of substance abuse treatment seeking following cocaine-related emergency
      department visits.
AB  - Chest pain is the most common medical complaint among cocaine-using emergency
      department (ED) patients. Correlates of substance abuse treatment seeking were
      examined using 3-month post-discharge surveys from 170 ED patients admitted with
      cocaine-related chest pain. Four treatment categories were specified as the
      dependent variable in an ordered logistic regression: no treatment (74.7%),
      informal treatment only (7.1%), formal treatment only (5.9%), and both formal and
      informal treatment (12.4%). The following variables were found to be positively
      associated with a higher treatment category: frequency of cocaine use (OR = 1.07,
      CI(95) = 1.01-1.15, p = 0.03), global severity index (OR = 2.26, CI(95) = 1.04
      4.90, p = 0.04), number of endorsed stigma barriers (OR = 4.40, CI(95) = 1.41
      13.78, p = 0.01), interpersonal consequences (OR = 1.41, CI(95) = 1.01-1.88, p =
      0.02), and pre-baseline informal treatment (OR = 6.69, CI(95) = 1.58-28.36, p =
      0.01). Physical consequences were found to be negatively associated with a higher
      treatment category (OR = 0.63, CI(95) = 0.47-0.85, p < 0.01). ED visits for
      cocaine-related chest pain represent missed opportunities to link patients to
      substance abuse treatment, and interventions are needed to motivate patients to
      seek care.

PMID- 20700661
TI  - Effects of early IL-17A neutralization on disease induction in a primate model of
      experimental autoimmune encephalomyelitis.
AB  - We report on the effect of antibody-mediated neutralization of interleukin (IL)
      17A in a non-human primate experimental autoimmune encephalomyelitis (EAE) model
      induced with recombinant human myelin oligodendrocyte glycoprotein (rhMOG). We
      tested a human-anti-human IL-17A-antibody in two doses (3 and 30 mg/kg) against
      placebo (PBS). The treatment was started 1 day before EAE induction and continued
      throughout the experiment. Although all monkeys developed clinically evident EAE,
      the onset of neurological signs was delayed in some monkeys from both treatment
      groups. Total CNS lesion volumes, demyelination, or inflammation did not differ
      between the different groups. Immune profiling revealed an altered distribution
      of IL-17A producing cells in the lymphoid organs of antibody-treated monkeys.
      Comparable numbers of IL-17A producing cells were observed in the brain. RhMOG
      induced T cell proliferation in the lymph nodes was slightly reduced after anti
      IL-17A antibody treatment. To summarize, we found that anti-IL-17A antibody as a
      single treatment from disease induction effects a trend towards delayed
      neurological disease progression in the marmoset EAE model, although the effect
      did not reach statistical significance. This suggests a role of IL-17A in late
      stage disease in the marmoset EAE model, but IL-17A may not be the dominant
      pathogenic cytokine.

PMID- 20700662
TI  - Real-time tracking of liver motion and deformation using a flexible needle.
AB  - PURPOSE: A real-time 3D image guidance system is needed to facilitate treatment
      of liver masses using radiofrequency ablation, for example. This study
      investigates the feasibility and accuracy of using an electromagnetically tracked
      flexible needle inserted into the liver to track liver motion and deformation.
      METHODS: This proof-of-principle study was conducted both ex vivo and in vivo
      with a CT scanner taking the place of an electromagnetic tracking system as the
      spatial tracker. Deformations of excised livers were artificially created by
      altering the shape of the stage on which the excised livers rested. Free
      breathing or controlled ventilation created deformations of live swine livers.
      The positions of the needle and test targets were determined through CT scans.
      The shape of the needle was reconstructed using data simulating multiple embedded
      electromagnetic sensors. Displacement of liver tissues in the vicinity of the
      needle was derived from the change in the reconstructed shape of the needle.
      RESULTS: The needle shape was successfully reconstructed with tracking
      information of two on-needle points. Within 30 mm of the needle, the registration
      error of implanted test targets was 2.4 +/- 1.0 mm ex vivo and 2.8 +/- 1.5 mm in
      vivo. CONCLUSION: A practical approach was developed to measure the motion and
      deformation of the liver in real time within a region of interest. The approach
      relies on redesigning the often-used seeker needle to include embedded
      electromagnetic tracking sensors. With the nonrigid motion and deformation
      information of the tracked needle, a single- or multimodality 3D image of the
      intraprocedural liver, now clinically obtained with some delay, can be updated
      continuously to monitor intraprocedural changes in hepatic anatomy. This
      capability may be useful in radiofrequency ablation and other percutaneous
      ablative procedures.

PMID- 20700663
TI  - Electronic device for endosurgical skills training (EDEST): study of reliability.
AB  - PURPOSE: Minimally Invasive Surgery procedures are commonly used in many surgical
      practices, but surgeons need specific training models and devices due to its
      difficulty and complexity. In this paper, an innovative electronic device for
      endosurgical skills training (EDEST) is presented. A study on reliability for
      this device was performed. METHOD: Different electronic components were used to
      compose this new training device. The EDEST was focused on two basic laparoscopic
      tasks: triangulation and coordination manoeuvres. A configuration and statistical
      software was developed to complement the functionality of the device. A
      calibration method was used to assure the proper work of the device. A total of
      35 subjects (8 experts and 27 novices) were used to check the reliability of the
      system using the MTBF analysis. RESULTS: Configuration values for triangulation
      and coordination exercises were calculated as 0.5 s limit threshold and 800
      11,000 lux range of light intensity, respectively. Zero errors in 1,050
      executions (0%) for triangulation and 21 errors in 5,670 executions (0.37%) for
      coordination were obtained. A MTBF of 2.97 h was obtained. CONCLUSIONS: The
      results show that the reliability of the EDEST device is acceptable when used
      under previously defined light conditions. These results along with previous work
      could demonstrate that the EDEST device can help surgeons during first training
      stages.

PMID- 20700664
TI  - Understanding clinical teachers: looking beyond assessment scores.

PMID- 20700665
TI  - Between-visit workload in primary care.
AB  - BACKGROUND: The time spent and complexity of work done by primary internal
      medicine physicians between office visits has not been well studied. OBJECTIVE:
      To measure the time and complexity of this care. DESIGN: Cross-sectional study.
      SETTING: General internists practicing on primary care teams with electronic
      medical records at a tertiary Veterans Health Administration Medical Center.
      PARTICIPANTS: Ten physicians. MAIN MEASURES: The project was designed to measure
      physician work between office visits. The electronic record was used to record
      the number and complexity of work events by physicians for 1 month. Complexity of
      work was measured on five levels ranging from Level I with no change in
      management, Level II with change in management of one disease, Level III of two
      diseases, Level IV of three diseases, and Level V of four or more diseases. Time
      sampling was done over 5 days to determine the time spent by level of complexity.
      Total time per physician was calculated by multiplying the number of events each
      physician captured by the average time for that physician for that level of
      complexity. KEY RESULTS: Physicians worked a median of 7.9 h per week between
      office visits. Work was apportioned among Level I (18.3%), Level II (38.3%),
      Level III (36.5%), Level IV (4.6%), and Level V (2.3%). LIMITATIONS: Single VA
      population and self-reported data. Findings may not be generalizable to other
      practice settings. CONCLUSION: Primary internists spent a median of 7.9 h per
      week in work between office visits with 82% of the time involved in changes in
      management.

PMID- 20700666
TI  - Judicious use of recombinant TSH in the management of differentiated thyroid
      carcinoma.
AB  - OBJECTIVE: To evaluate the feasibility of using recombinant human TSH (rhTSH) in
      conjunction with 131I to treat patients with differentiated thyroid carcinoma.
      METHODS: Between July 2003 and April 2009, 14 patients [mean age, 39.1 years
      (range 14-71 years)], of whom seven were treated for remnant ablation and seven
      for irresectable or metastatic disease, received rhTSH-aided 131I therapy. None
      had an adequate rise in TSH. The mean 131I dosage administered was 5206.3 MBq.
      Baseline thyroglobulin/anti-thyroglobulin (Tg/anti-Tg) and TSH levels were
      documented. rhTSH (0.9 mg) was given intramuscularly on days 1 and 2, and TSH
      levels were recorded. 131I was given when the TSH level rose to >30 MUIU/ml.
      Tg/anti-Tg levels were measured at 3-month intervals. A 131I whole-body scan
      (131I scan) was performed 6 or 12 months after treatment. RESULTS: The baseline
      median valid Tg and TSH levels were 76.2 ng/ml (range 14.1 to >30000) and 3.63
      MUIU/ml (range 1.36-11.0), respectively. The rise in TSH level was 34.8-96.9
      MUIU/ml after the first rhTSH injection and 33.1 to >75 MUIU/ml after the second
      injection. The post-therapy 131I scan showed uptake at disease sites in all
      patients, indicating the initial empirical adequacy of treatment. Follow-up 131I
      scan was positive for four patients, but negative for three of these patients
      after subsequent therapy. Complete resolution of disease was seen in eight
      patients and partial resolution in four after 3 months of therapy; one had stable
      disease; and in one patient with progressive disease, complete resolution was
      achieved after repeated 131I doses with thyroxine withdrawal. After a median
      follow-up of 39.2 months, all patients were alive and no disease recurrence was
      observed. The overall response rate at 3 months was 86% and had improved to 93%
      at the time of this review. The final ablation rate in seven patients was 100%.
      Apart from notable neck swelling in four patients, which was responsive to
      medication, and headache in two patients, no significant short-term side-effects
      of therapy were seen. CONCLUSION: In our setting, the use of rhTSH-aided 131I
      ablation and treatment was safe and effective.

PMID- 20700667
TI  - A practical method of determining cross-calibration factors of PET scanners by
      moving a point-like (22)Na radioactive source.
AB  - PURPOSE: Thus far, cylindrical phantoms with (18)F or (68)Ge/(68)Ga have been
      used in the standard techniques for determining the cross-calibration factors
      (CCFs) of PET scanners. This paper describes a new practical method that uses a
      point-like (22)Na radioactive source for determining CCFs. METHODS: A point-like
      (22)Na radioactive source (about 700 kBq) was equipped with a spherical aluminium
      absorber capsule to ensure the symmetry of the emitted photons. During
      measurements, the source was moved in the axial direction to cover the whole
      axial field of view (FOV) of a clinical PET scanner, SET-2400 W. The region-of
      interest (ROI) values obtained in reconstructed images without scatter and
      attenuation corrections were used to calculate the CCFs of the PET scanner.
      RESULTS: The CCFs obtained by the proposed method agreed with those obtained by
      the standard cross-calibration (CC) method within a precision of 1.5% (sigma).
      The temporal variations in the CCFs by the standard CC method were reproduced by
      the proposed method with a precision better than 1%. CONCLUSION: The CC method
      with a moving (22)Na point-like radioactive source is practically useful for
      determining the CCFs of PET scanners and monitoring their variations.

PMID- 20700669
TI  - Severe hemophilia A in a Japanese female caused by an F8-intron 22 inversion
      associated with skewed X chromosome inactivation.

PMID- 20700670
TI  - Case report: A technique to remove a jammed locking screw from a locking plate.
AB  - BACKGROUND: Locking titanium plates revolutionized the treatment of osteoporotic
      and metaphyseal fractures of long bones. However as with any innovation, with
      time new complications are identified. One of the problems with titanium locking
      plates is removal of screws, often attributable to cold welding of screw heads
      into the locking screw holes. Several techniques have been described to overcome
      this problem. We describe a new easy technique to remove a jammed locking screw
      in a locking plate that is easily reproducible and suggest an algorithm to
      determine the method to remove screws from locking plates. CASE DESCRIPTION: A 57
      year-old man underwent removal of a locking titanium plate from the distal femur.
      Because the screws could not be readily removed, we used a new technique to
      remove the jammed locking screws. A radial cut was made in the plate into the
      locking screw hole and wedged with an osteotome. This released the screw head
      from the locking screw hole. The screw holes were connected with radial cuts and
      jammed locking screws were removed in a similar fashion. LITERATURE REVIEW:
      Instruments used for removal of locking screws, including conical extraction
      screws, hollow reamers, extraction bolts, modular devices, and carbide drill
      bits, have been described. However, these do not always work. PURPOSES AND
      CLINICAL RELEVANCE: Removing screws from locking titanium plates can be
      difficult. There is no method of implant removal that can be universally applied.
      Therefore, this new technique and our algorithm may be used when removing screws
      from locking titanium plates.

PMID- 20700671
TI  - When can I drive?: brake response times after contemporary total knee
      arthroplasty.
AB  - BACKGROUND: After right total knee arthroplasty (TKA), patients are usually eager
      to return to driving. Previous studies suggest 6 weeks postsurgery is a safe
      time. However, recent advances in surgical technique, pain management, and
      rehabilitation have theoretically improved recovery after TKA.
      QUESTIONS/PURPOSES: We therefore determined if (1) the timeframe for return to
      driving, as determined by attainment of preoperative braking levels, would be
      shorter after contemporary right TKA than that reported previously for a
      traditional TKA; and (2) gender or age influence recovery of baseline response
      time. METHODS: Brake response times for all 29 patients undergoing right-sided
      TKA between January 17, 2008, and January 29, 2009, were scheduled to be measured
      by a trained occupational therapist before surgery and at 4, 6, and 8 weeks after
      surgery. For each patient, testing was discontinued once the preoperative level
      was achieved. RESULTS: All patients returned to baseline braking levels by 4
      weeks after surgery. Gender and age did not influence recovery times.
      CONCLUSIONS: If other requirements for driving are met, surgeons may consider
      allowing patients treated with contemporary right TKAs to drive 4 weeks after
      surgery.

PMID- 20700672
TI  - Is there a risk in placing a ceramic head on a previously implanted trunion?
AB  - BACKGROUND: Strategies for revising a ceramic-on-ceramic total hip prosthesis are
      controversial. Some consider reimplantation of a ceramic head on a well-fixed
      femoral stem inadvisable as it may lead to a fracture of the newly implanted
      head. QUESTIONS/PURPOSES: We assessed (1) the risk of fracture when a new ceramic
      head was placed on a previously implanted trunion; (2) the survival rate of the
      revised hips; and (3) hip function and acetabular and femoral component loosening
      at midterm followup. PATIENTS AND METHODS: We retrospectively reviewed all 126
      patients (139 hips) who had revision of alumina-alumina hip arthroplasties
      between January 1977 and December 2005. Of these, 99 patients (110 hips) had
      revision of the socket only with retention of the femoral component. The femoral
      head was left in place in 33 hips, the same alumina head was re-implanted in
      seven hips, a new alumina head was implanted in 45 hips, a metallic head in 16,
      and a zirconia head in nine. Twenty-six patients (29 hips) died and nine (10
      hips) were lost to followup before 5 years; this left 71 hips for review. Minimum
      followup was 60 months (mean, 112 months; range, 60-319 months). RESULTS:
      Eighteen hips required rerevision surgery, 11 for aseptic loosening, two for
      septic loosening, two for fracture of a ceramic liner, one for recurrent
      dislocation, one for ipsilateral femoral fracture, and one for unexplained pain.
      Among the 61 ceramic heads implanted on a well-fixed stem, no fracture of the
      head occurred at a mean 88 months' followup. The survival rate at 10 years with
      mechanical failure as the end point was 81.6%. CONCLUSIONS: We observed no
      fractures of the ceramic heads implanted on a previous titanium trunion. This
      approach is possible if inspection shows no major imperfection of the Morse
      taper.

PMID- 20700673
TI  - Patient perceived outcomes after primary hip arthroplasty: does gender matter?
AB  - BACKGROUND: Total hip arthroplasty (THA) provides high functional scores and long
      term survivorship. However, differences in function and disability between men
      and women before and after arthroplasty are not well understood.
      QUESTIONS/PURPOSES: We determined if there was a gender difference in patient
      perceived functional measures and range of motion in primary THA. METHODS: We
      retrospectively studied 532 patients (658 hips) undergoing primary THA. A total
      of 59% were women and 41% were men. Patients were assessed preoperatively and at
      minimum 2 years using Quality of Well-being, SF-36, WOMAC, and Harris hip score.
      We determined if differences existed between genders before and at followup for
      all dependent measures. Independent t-tests were also used to determine
      differences between genders concerning the change (Delta) scores and hip range of
      motion. The time course of perceived functional recovery was also documented.
      RESULTS: Males were on average 5 years (58) younger than females (63). Before
      surgery, females scored worse than males on the Harris hip score, WOMAC function,
      WOMAC pain, and WOMAC total scores. All scores improved at followup in both
      groups. Regardless of time, females had lower scores than males. However, females
      had greater improvement over males for WOMAC function (39 versus 35), WOMAC pain
      (11 versus 10), and WOMAC total (53 versus 48). CONCLUSIONS: Substantial gender
      functional differences exist before treatment. However, women reported greater
      improvement as a result of the intervention when compared with men. LEVEL OF
      EVIDENCE: Level III, prognostic study. See Guidelines for Authors for a complete
      description of levels of evidence.

PMID- 20700674
TI  - Knee arthroplasty with a medially conforming ball-and-socket tibiofemoral
      articulation provides better function.
AB  - BACKGROUND: A knee design with a ball-and-socket articulation of the medial
      compartment has a femoral rollback profile similar to the native knee. Compared
      to a conventional, posterior-stabilized knee design, it provides AP stability
      throughout the entire ROM. However, it is unclear whether this design difference
      translates to clinical and functional improvement. QUESTIONS/PURPOSES: We asked
      whether the medially conforming ball-and-socket design differences would be
      associated with (1) improved ROM; and (2) improved American Knee Society, WOMAC,
      Oxford Knee, SF-36, and Total Knee Function Questionnaire scores compared to a
      conventional, fixed-bearing posterior-stabilized TKA. PATIENTS AND METHODS: We
      enrolled 82 patients in a single-center, single-blinded, randomized, controlled
      trial comparing the medially conforming ball-and-socket design knee prosthesis to
      a posterior-stabilized total knee prosthesis. Our primary end point was ROM. Our
      secondary end points were American Knee Society, WOMAC, Oxford Knee, SF-36, and
      Total Knee Function Questionnaire scores. All patients were followed at 1 and 2
      years. RESULTS: The mean ROM was 100.1 degrees  and 114.9 degrees  in the
      posterior-stabilized and medially conforming ball-and-socket groups,
      respectively. The physical component scores of SF-36 and Total Knee Function
      Questionnaire were better in the medially conforming ball-and-socket group. We
      found no difference in American Knee Society, WOMAC, and Oxford Knee scores.
      CONCLUSIONS: Both implant designs similarly relieved pain and improved function.
      The medially conforming ball-and-socket articulation provided better high-end
      function as reflected by the Total Knee Function Questionnaire. LEVEL OF
      EVIDENCE: Level I, therapeutic study. See Guidelines for Authors for a complete
      description of levels of evidence.

PMID- 20700675
TI  - Algorithm for femoral and periacetabular osteotomies in complex hip deformities.
AB  - BACKGROUND: Residual acetabular dysplasia of the hip in most patients can be
      corrected by periacetabular osteotomy. However, some patients have intraarticular
      abnormalities causing insufficient coverage, containment or congruency after
      periacetabular osteotomy, or extraarticular abnormalities that limit either
      acetabular correction or hip motion. For these patients, we believe an additional
      proximal femoral osteotomy can improve coverage, containment, congruency and/or
      motion. PURPOSES: We provide algorithms for (1) identifying patients we believe
      will benefit from proximal femoral osteotomy, (2) selecting the appropriate
      osteotomy, and (3) choosing the sequence of these osteotomies. METHODS:
      Anteroposterior, false-profile and functional radiographs and MR can identify
      most patients we believe will benefit from periacetabular and femoral
      osteotomies. Recently described techniques, including relative femoral neck
      lengthening, femoral neck osteotomy and femoral head osteotomy have expanded
      indications for a combined procedure. Historically performed first,
      periacetabular osteotomy is now frequently performed following femoral osteotomy.
      RESULTS: The rate of intertrochanteric osteotomy performed with periacetabular
      osteotomy has decreased from approximately 10% in the first 500 surgeries to
      about 2% currently. Among 151 relative neck lengthenings (23 with PAO), 53
      femoral neck osteotomies (4 with PAO) and 14 femoral head osteotomies (11 with
      PAO), eleven complications occurred including osteonecrosis in two and delayed
      unions in eight. No complication occurred following a combined procedure.
      CONCLUSION: Although isolated periacetabular osteotomy can provide sufficient
      coverage, containment and congruency for most patients with residual hip
      dysplasia, some may benefit from an additional proximal femoral osteotomy.
      Knowing the appropriate indications, selection, and sequencing of these
      osteotomies is critical for enhancing patient outcomes.

PMID- 20700676
TI  - Local recurrence after initial multidisciplinary management of soft tissue
      sarcoma: is there a way out?
AB  - BACKGROUND: Multimodality treatment of primary soft tissue sarcoma by expert
      teams reportedly affords a low incidence of local recurrence. Despite advances,
      treatment of local recurrence remains difficult and is not standardized.
      QUESTIONS/PURPOSES: We (1) determined the incidence of local recurrence from soft
      tissue sarcoma; (2) compared characteristics of the recurrent tumors with those
      of the primary ones; (3) evaluated local recurrences, metastases and death
      according to treatments; and (4) explored the relationship between the diagnosis
      of local recurrence and the occurrence of metastases. METHODS: From our
      prospective database, we identified 618 soft tissue sarcomas. Thirty-seven of the
      618 patients (6%) had local recurrence. Leiomyosarcoma was the most frequent
      diagnosis (eight of 37). The mean delay from original surgery was 22 months
      (range, 2-75 months). Mean size was 4.8 cm (range, 0.4-28.0 cm). Median followup
      after local recurrence was 16 months (range, 0-98 months). RESULTS: Recurrent
      tumors had a tendency toward becoming deeper seated and higher graded. Nineteen
      of the 37 patients with recurrence underwent limb salvage (nine free flaps) and
      six had an amputation. Twenty-two (59%) had metastases, including 10 occurring
      after the local recurrence event at an average delay of 21 months (range, 1-34
      months). Six patients developed additional local recurrences, with no apparent
      difference in risk between amputation (two of six) and limb salvage (four of 19).
      CONCLUSIONS: Patients with a local recurrence of a soft tissue sarcoma have a
      poor prognosis. Limb salvage and additional radiotherapy remain possible but with
      substantial complications. Amputation did not prevent additional local recurrence
      or death.

PMID- 20700678
TI  - Total costs and atrial fibrillation ablation success or failure in Medicare-aged
      patients in the United States.
AB  - INTRODUCTION: This retrospective cohort study compared the direct medical costs
      of successful versus unsuccessful catheter ablation in Medicare-aged patients
      with atrial fibrillation (AF), using medical claims data. METHODS: AF patients
      with > or = 12 months of continuous medical/pharmacy coverage pre- and
      postablation were identified from the MarketScan Medicare database (January 2003
      to December 2006). For study inclusion, patients were required to have > or = 2
      AF inpatient/outpatient visits within 6 months and to have received
      antiarrhythmic drug therapy within 12 months prior to the index ablation.
      Ablation success was defined as the absence of antiarrhythmic drug therapy 6-12
      months postablation. RESULTS: Of 135 patients identified (67% men, mean age 73
      years), ablation was successful in 69 (51.1%); most patients (96%) underwent a
      single procedure. Patients with successful ablation discontinued antiarrhythmic
      drug treatment after (mean) 54 days. Use of rate-control and anticoagulant drugs
      decreased after successful ablation, from 87% to 67% and from 86% to 64% of
      patients, respectively. Among failed ablation patients, 74% versus 70% received
      rate-control drugs, and 88% versus 82% received anticoagulants pre- versus
      postablation. Mean +/- SD per-patient procedural costs were $13,655+/-$12,761 for
      successful compared with $17,294+/-$26,502 (P=0.21) for failed ablation, while AF
      related medical costs over 12 months postablation were $2394+/-$642 and $2703+/
      $1706, respectively (P<0.001). Overall costs tended to be lower for successful
      ($16,049+/-$12,536) than for failed ($19,997+/-$13,958) AF ablation (P=0.07).
      These findings are subject to the limitations imposed by a retrospective database
      analysis and a small sample size. CONCLUSION: Outside the clinical-trial setting,
      catheter ablation for second-line treatment of AF proved unsuccessful in half of
      Medicare-aged patients. Direct medical costs did not differ significantly between
      patients with failed and successful ablations. The high rate and costs of AF
      ablation failure in the Medicare-aged population reinforce the need for better
      understanding of prognostic factors for ablation outcome.

PMID- 20700677
TI  - Increased chondrocyte death after steroid and local anesthetic combination.
AB  - BACKGROUND: Hyaline articular cartilage has limited repair and regeneration
      capacity. Intraarticular administration of glucocorticoid and local anesthetic
      injections play an important role in the therapy of osteoarthritis.
      Glucocorticoids and anesthetics reportedly enhance apoptosis in chondrocytes, but
      effects of the combined use of glucocorticoids and local anesthetics are unknown.
      QUESTIONS/PURPOSES: We asked whether glucocorticoid and local anesthetic agents
      combined had any synergistic effects on chondrocyte apoptosis. METHODS: Cell
      viability and apoptosis/necrosis assessment of human articular chondrocytes were
      performed in vitro (chondrocyte cell cultures) and ex vivo (osteochondral
      specimens) using flow cytometry and TUNEL analysis, respectively. RESULTS:
      Glucocorticoids and local anesthetics induce apoptosis in chondrocytes at various
      rates. When used in combination, the percentage of dead chondrocytes was
      increased in in vitro chondrocyte cell cultures and osteochondral ex vivo
      specimens. CONCLUSIONS: We observed a time-dependent decrease in chondrocyte
      viability after concurrent steroid and local anesthetic exposure. CLINICAL
      RELEVANCE: The combination of glucocorticoids and local anesthetics has an
      adverse effect on articular chondrocytes, and it raises a question regarding
      whether concomitant administration should be used in treating osteoarthritis.

PMID- 20700679
TI  - Noninvasive monitoring the biology of atherosclerotic plaque development with
      radiolabeled annexin V and matrix metalloproteinase inhibitor in spontaneous
      atherosclerotic mice.
AB  - OBJECTIVES: To compare the ability of (99m)Tc-labeled broad-based matrix
      metalloproteinase inhibitor (RP805) (MPI) and (99m)Tc-annexin V to identify more
      advanced atherosclerotic disease in apolipoprotein E-null (apoE(-/-)) mice.
      BACKGROUND: Both MMP expression and apoptotic cell death occur in both early and
      in advanced atherosclerotic plaques. METHODS: Eight 6-9-week-old apoE(-/-) mice,
      10 apoE(-/-) mice at 20 weeks, and 12 apoE(-/-) at 40 weeks were injected with
      both tracers in alternating sequence separated by 48 h, underwent planar imaging
      and were killed. Radiotracer uptake was quantified from the scans as percent
      whole body and from tissue as percent injected dose per gram (%ID/g).
      Quantitative immunohistopathology of the aorta and carotids for macrophages,
      MMPs, and caspase was performed. RESULTS: At 6 weeks, mice showed no tracer
      uptake in the chest or neck and had minimal lesion. At 20 weeks, uptake of
      annexin V as %ID was borderline higher than MPI (1.10 +/- .48% vs .77 +/- .31%, P
      = .09), between 20 and 40 weeks aortic lesion area increased from 37.4 +/- 12.0%
      to 46.2 +/- 7.4% and at 40 weeks MPI was significantly greater than annexin V
      uptake (1.11 +/- .66% vs .70 +/- .16%, P = .05). On histology there were greater
      increases in % MMP-2 and -9 than % caspase positive cells. Carotid uptake of MPI
      was greater than annexin V at both 20 and 40 weeks (1.25 +/- .48% vs .78 +/-
      .25%, P = .02 and 3.70 +/- 1.45% vs 2.25 +/- .66%, P = .005). The carotid lesion
      area at 40 weeks was 74 +/- 9% with greater % cells positive for MMP's than
      caspase. %ID/g annexin V correlated significantly with % macrophages and with
      caspase-3 positive cells and %ID/g MPI correlated significantly with %
      macrophages and with MMP-2 and -9 positive cells. CONCLUSIONS: In apoE(-/-) mice,
      MMP expression is greater than apoptosis as the disease progresses and MPI may be
      a better imaging agent for more advanced disease.

PMID- 20700680
TI  - Comparative efficacy of ultrasound-guided and stimulating popliteal-sciatic
      perineural catheters for postoperative analgesia.
AB  - PURPOSE: Perineural catheter insertion using ultrasound guidance alone is a
      relatively new approach. Previous studies have shown that ultrasound-guided
      catheters take less time to place with high placement success rates, but the
      analgesic efficacy compared with the established stimulating catheter technique
      remains unknown. We tested the hypothesis that popliteal-sciatic perineural
      catheter insertion relying exclusively on ultrasound guidance results in superior
      postoperative analgesia compared with stimulating catheters. METHODS:
      Preoperatively, subjects receiving a popliteal-sciatic perineural catheter for
      foot or ankle surgery were assigned randomly to either ultrasound guidance (bolus
      via needle with non-stimulating catheter insertion) or electrical stimulation
      (bolus via catheter). We used 1.5% mepivacaine 40 mL for the primary surgical
      nerve block and 0.2% ropivacaine (basal 8 mL.hr(-1); bolus 4 mL; 30 min lockout)
      was infused postoperatively. The primary outcome was average surgical pain on
      postoperative day one. RESULTS: Forty of the 80 subjects enrolled were randomized
      to each treatment group. One of 40 subjects (2.5%) in the ultrasound group failed
      catheter placement per protocol vs nine of 40 (22.5%) in the stimulating catheter
      group (P = 0.014). The difference in procedural duration (mean [95% confidence
      interval (CI)]) was -6.48 (-9.90 - -3.05) min, with ultrasound requiring 7.0 (4.0
      14.1) min vs stimulation requiring 11.0 (5.0-30.0) min (P < 0.001). The average
      pain scores of subjects who provided data on postoperative day one were somewhat
      higher for the 33 ultrasound subjects than for the 26 stimulation subjects (5.0
      [1.0-7.8] vs 3.0 [0.0-6.5], respectively; P = 0.032), a difference (mean [95%CI])
      of 1.37 (0.03-2.71). CONCLUSION: For popliteal-sciatic perineural catheters,
      ultrasound guidance takes less time and results in fewer placement failures
      compared with stimulating catheters. However, analgesia may be mildly improved
      with successfully placed stimulating catheters. Clinical trial registration
      number NCT00876681.

PMID- 20700681
TI  - Hemodynamic effects of lipid emulsion after local anesthetic intoxication may be
      due to a direct effect of fatty acids on myocardial voltage-dependent calcium
      channels.

PMID- 20700682
TI  - Alkaloids extracted from Pterogyne nitens induce apoptosis in malignant breast
      cell line.
AB  - In the present study, two alkaloids isolated from Pterogyne nitens, a plant
      native to Brazil, have been shown to induce apoptosis in human breast cancer
      cells. These compounds, pterogynine (PGN) and pterogynidine (PGD), were tested
      for their effect on a human infiltrating ductal carcinoma cell line (ZR-7531).
      The cell line was treated with each alkaloid at several concentrations. Time
      dependence (with or without recuperation time) and concentration-dependence (in
      the range 0.25-10 mM) were investigated in cytotoxicity and apoptosis assays. The
      annexin assay indicated an apparently higher percentage of death by necrosis of
      malignant cells after 24 h exposure to both P. nitens extracts than the Hoechst
      assay. Thus, our results in the two tests demonstrated that the Hoechst assay can
      discriminate between late apoptotic cells and necrosis, whereas the flow
      cytometry-based annexin V assay cannot. We concluded that PGN and PGD have
      effective antineoplastic activity against human breast cancer cells in vitro, by
      inducing programmed cell death.

PMID- 20700683
TI  - [Cerebrospinal fluid-based diagnostics of CT-negative subarachnoid haemorrhage].
AB  - The diagnostic investigation of CT-negative subarachnoid haemorrhage (SAH) is a
      particular challenge in clinical neurology. Cerebrospinal fluid (CSF) analysis
      via lumbar puncture is the method of choice. The diagnosis of SAH in CSF is based
      on a bloody or xanthochromic discoloration of the CSF as well as on findings in
      non-automated CSF cytology including the detection of erythrophages and
      siderophages. The automated determination of CSF ferritin concentrations or
      spectrophotometric detection of xanthochromia may contribute to the diagnosis but
      are only useful with regard to the overall clinical picture. Generally, the
      knowledge of the time flow of CSF changes associated with SAH is essential for a
      correct interpretation of CSF findings.

PMID- 20700684
TI  - [DGPPN Young Physician Campaign 10: "Demonstrating our capacity!" On the status
      of graduate education in the psychiatry and psychotherapy specialty].

PMID- 20700687
TI  - Identification of proteins responsible for the multiple drug resistance in 5
      fluorouracil-induced breast cancer cell using proteomics analysis.
AB  - PURPOSE: This study aimed to explore the mechanism of multi-drug resistance (MDR)
      in 5-fluorouracil (5-FU)-induced breast cancer cell MCF-7. METHODS: MCF-7 cells
      were exposed in stepwise escalating concentration of 5-FU to develop the
      resistant cell line, MCF-7/5-FU. Biological and molecular characteristics of the
      cells were studied through MTT, flow cytometry, real-time PCR, western-blot, and
      the global protein profiles between MCF-7/5-FU and parental MCF-7 were compared
      using proteomic approach. Then some of the differentially expressed proteins were
      validated by western-blot. In addition, the role of 14-3-3sigma was validated
      using gene transfection. RESULTS: Drug resistance of MCF-7/5-FU cells to 5-FU,
      MX, cDDP, ADM, TAXOL all increased significantly compared with MCF-7 cells and
      that maybe related to BCRP, but not MDR1 and MRP1. Differentially expressed
      proteins between MCF-7/5-FU and MCF-7 cells were identified; 12 proteins were up
      regulated and 18 proteins were down-regulated in MCF-7/5-FU cells. Expressive
      levels of some proteins in western-blot validation were consistent with the
      results in proteomic analysis. Enforced 14-3-3sigma expression can increase the
      sensitivity of MCF-7/5-FU cells to 5-FU and cDDP. CONCLUSION: MDR of MCF-7/5-FU
      likely associated with differentially expressed proteins and 14-3-3sigma may play
      a positive role in chemotherapy. These findings may provide theoretical support
      for the prediction of chemotherapeutic response and reverse of MDR.

PMID- 20700688
TI  - Biphasic effect of a primary tumor on the growth of secondary tumor implants.
AB  - BACKGROUND: The phenomenon of hormesis is characterized by a biphasic dose
      response, exhibiting opposite effects in the low- and high-dose zones. In this
      study, we explored the possibility that the hormesis concept may describe the
      interactions between two tumors implanted in a single mouse, such that the
      resulting tumors are of different sizes. MATERIALS AND METHODS: We used two
      murine tumors of spontaneous origin and undetectable immunogenicity growing in
      BALB/c mice. A measure of cell proliferation was obtained by immunostaining for
      Ki-67 protein and by using the [(3)H] thymidine uptake assay. For serum
      fractionation, we utilized dialysis and chromatography on Sephadex G-15. RESULTS:
      The larger primary tumor induced inhibitory or stimulatory effects on the growth
      of the smaller secondary one, depending on the ratio between the mass of the
      larger tumor relative to that of the smaller one, with high ratios rendering
      inhibition and low ratios inducing stimulation of the secondary tumor.
      CONCLUSION: Since metastases can be considered as natural secondary tumor
      implants in a tumor-bearing host and that they constitute the main problem in
      cancer pathology, the use of the concept of hormesis to describe those biphasic
      effects might have significant clinical implications. In effect, if the tumor
      bearing host were placed in the inhibitory window, tumor extirpation could
      enhance the growth of distant metastases and, reciprocally, if placed in the
      stimulatory window, tumor extirpation would result not only in a reduction or
      elimination of primary tumor load but also in a slower growth or inhibition of
      metastases.

PMID- 20700689
TI  - NMR with (13)C, (15)N-doubly-labeled DNA: The shape Antennapedia homeodomain
      complex with a 14-mer DNA duplex.
AB  - Nearly complete (1)H, (13)C and(15) N NMR assignments have been obtained for a
      doubly labeled 14-base pair DNA duplex in solution both in the free state and
      complexed with the uniformly (15)N-labeled Antennapedia homeodomain. The DNA was
      either fully (13)C,(15)N-labeled or contained uniformly (13)C, (15)N-labeled
      nucleotides only at those positions which form the protein-DNA interface in the
      previously determined NMR solution structure of the Antennapedia homeodomain-DNA
      complex. The resonance assignments were obtained in three steps: (i)
      identification of the deoxyribose spin systems via scalar couplings using 2D and
      3D HCCH-COSY and soft-relayed HCCH-COSY; (ii) sequential assignment of the
      nucleotides via(1) H-(1)H NOEs observed in 3D(13) C-resolved NOESY; and (iii)
      assignment of the imino and amino groups via (1)H-(1)H NOEs and(15) N-(1)H
      correlation spectroscopy. The assignment of the duplex in the 17 kDa protein-DNA
      complex was greatly facilitated by the fact that (1)H signals of the protein were
      filtered out in (13)C-resolved spectroscopy and by the excellent carbon chemical
      shift dispersion of the DNA duplex. Comparison of corresponding (13)C chemical
      shifts of the free and the protein-bound DNA indicates conformational changes in
      the DNA upon complex formation.

PMID- 20700690
TI  - Secondary H/D isotope effect on hydrogen-bonded hydroxyl groups as a tool for
      recognizing distance constraints in conformational analysis of oligosaccharides.
AB  - An 'isotopomer-selected NOE' (ISNOE) method for the unequivocal identification of
      mutually hydrogen-bond-linked hydroxyl groups is described. It relies on the fact
      that the OH group's signal patterns obtained for a partially deuterated sample
      originate from both isotopomers of the 'partner' hydroxyl, whereas a NOE for this
      group can originate from cross-relaxation with the protio isotopomer of this
      hydroxyl only. Hence, the isotopically shifted component of this group's signal
      does not appear in a ROE difference spectrum obtained with selective excitation
      of the 'partner' hydroxyl. This method is also applicable in those cases when
      only one of two mutually hydrogen-bonded groups exhibits resolvable isotope
      shifts. Furthermore, it is shown that isotope shifts may occur even for pairs of
      OH groups that are not mutually hydrogen-bonded, if these participate in hydrogen
      bonds with other hydroxyls and thereby affect conformational equilibria. The
      ISNOE experiment enables one to distinguish between these two sources of isotope
      shifts. Since the O[Symbol: see text][Symbol: see text][Symbol: see text]O
      distance for hydrogen-bonded hydroxyls in sugars is known to lie between 2.7 and
      3.0 A , the hydrogen bonds established by ISNOE can be used in conformational
      analysis as reliable, motionally non-averaged distance constraints for the
      conformations containing these bonds.

PMID- 20700691
TI  - An empirical relationship between rotational correlation time and solvent
      accessible surface area.
AB  - Structure-dynamics interrelationships are important in understanding protein
      function. We have explored the empirical relationship between rotational
      correlation times (tau(c) and the solvent accessible surface areas (SASA) of 75
      proteins with known structures. The theoretical correlation between SASA and
      tau(c) through the equation SASA = K(r)tau(c) ((2/3)) is also considered. SASA
      was determined from the structure, tau(c) (calc) was determined from diffusion
      tensor calculations, and tau(c) (expt) was determined from NMR backbone(13) C or
      (15)N relaxation rate measurements. The theoretical and experimental values of
      tau(c) correlate with SASA with regression analyses values of K(r) as 1696 and
      1896 m(2)s(-(2/3)), respectively, and with corresponding correlation coefficients
      of 0.92 and 0.70.

PMID- 20700692
TI  - A multilocus approach to assessing co-evolutionary relationships between
      Steinernema spp. (Nematoda: Steinernematidae) and their bacterial symbionts
      Xenorhabdus spp. (gamma-Proteobacteria: Enterobacteriaceae).
AB  - Nematodes of the genus Steinernema Travassos, 1927 (Nematoda: Steinernematidae)
      and their associated bacteria, Xenorhabdus spp. (gamma-Proteobacteria), are an
      emergent model of terrestrial animal-microbe symbiosis. Interest in this
      association initially arose out of their potential as biocontrol agents against
      insect pests, but, despite advances in their field application and the growing
      popularity of this model system, relatively little has been published to uncover
      the evolutionary facets of this beneficial partnership. This study adds to the
      body of knowledge regarding nematode-bacteria symbiosis by proposing a possible
      scenario for their historical association in the form of a cophylogenetic
      hypothesis. Topological and likelihood based testing methods were employed to
      reconstruct a history of association between 30 host-symbiont pairs and to gauge
      the level of similarity between their inferred phylogenetic patterns.

PMID- 20700693
TI  - A new tetraphyllidean genus and species, Caulopatera pagei n. g., n. sp.
      (Tetraphyllidea: Phyllobothriidae), from the grey carpetshark Chiloscyllium
      punctatum Muller & Henle (Orectolobiformes: Hemiscylliidae).
AB  - A new genus and species of tetraphyllidean cestode, Caulopatera pagei n. g., n.
      sp., is described from the grey carpetshark Chiloscyllium punctatum Muller &
      Henle in Moreton Bay, Australia. The new genus is placed in the Phyllobothriidae,
      subfamily Phyllobothriinae. Caulopatera n. g. is distinct from all other
      phyllobothriine genera in having stalked, circular, non-loculate bothridia that
      lack an apical sucker, testes that are restricted to the region anterior to the
      cirrus-sac and circum-medullary vitelline follicles. The new genus most closely
      resembles Carpobothrium Shipley & Hornell, 1906, with which it shares non
      loculate, stalked, unhooked bothridia without an accessory sucker and testes that
      are entirely anterior to the cirrus-sac, but differs from it in that it lacks a
      slit-like opening in each bothridium and flaps surrounding the opening. The
      possession of bothridial stalks is consistent with two cestode orders, the
      Tetraphyllidea and the Rhinebothriidea. The morphology of the bothridial stalks
      is consistent with other tetraphyllidean genera, in that Caulopatera possesses
      triangular bothridial stalks surrounding the back of the bothridia, indicating
      that it belongs in the Tetraphyllidea senso stricto, rather than in the recently
      recognised Rhinebothriidea.

PMID- 20700694
TI  - Rhabdias lacertae n. sp. (Nematoda: Rhabdiasidae), the first rhabdiasid species
      parasitising lizards in Europe.
AB  - A new nematode species, Rhabdias lacertae n. sp. (Rhabdiasidae), is described
      from the body-cavity of the common lizard Lacerta vivipara Jacquin (Lacertidae)
      from the Ridge of Mala Fatra (Sokolie Hill), north-western Slovakia. The new
      species differs from its congeners mainly in possessing 3 min cuticular spikes at
      the tail tip and some other features. This is the first species of Rhabdias
      Stiles & Hassall, 1905 described from lizards in Europe and the first species of
      this genus parasitising hosts belonging to the Lacertidae.

PMID- 20700695
TI  - Morphology and diagnosis of the fourth-stage larva of Coronocyclus labratus
      (Looss, 1900) (Nematoda: Strongyloidea) parasitising equids.
AB  - The fourth larval stage (L4) of Coronocyclus labratus (Looss, 1900) Hartwich,
      1986, one of the common species of the Cyathostominae found in equids, is
      identified and described. The larvae found were identified as C. labratus by
      finding moulting forms possessing characters of both larval and adult stages. The
      larvae are similar to those of Cylicocyclus leptostomum (Kotlan, 1920) Foster,
      1936, Cyathostomum catinatum Looss, 1900 and Cylicostephanus goldi (Boulenger,
      1917) Lichtenfels, 1975. The buccal capsule (BC) wall of the L4 of Cylicocyclus
      leptostomum is thinner than that of Coronocyclus labratus, and the ring of the
      oesophageal funnel is comparatively less well developed. In C. labratus the
      dorsal tooth protrudes only slightly into the buccal cavity, and this larva
      possesses a characteristically elongate, pyriform oesophagus. In Cyathostomum
      catinatum, the BC walls are thicker than in Coronocyclus labratus, and the dorsal
      tooth is more bluntly pointed. Sublateral teeth, if present, are bluntly pointed
      in the former species, but usually absent or indistinct in C. labratus. Larvae of
      Cylicostephanus goldi differ from those of Coronocyclus labratus in the larger
      size of the BC.

PMID- 20700696
TI  - Alcicornis haroldi n. sp. (Digenea: Bucephalidae) from the yellowspotted trevally
      Carangoides fulvoguttatus (Forsskal) (Carangidae) from off New Caledonia.
AB  - Alcicornis haroldi n. sp. is described from Carangoides fulvoguttatus from off
      New Caledonia, South Pacific. It differs from all other Alcicornis spp. in its
      large protuberant pharynx, and from the most similar species, A. baylisi Nagaty,
      1937, in its broader rhynchus, indistinct withdrawn tentacles and vitelline
      distribution.

PMID- 20700697
TI  - The erection of Pelecanema n. g. (Nematoda: Spirurida: Acuariidae), with
      redescriptions of P. sirry (Khalil, 1931) n. comb. and P. pelecani (Johnston &
      Mawson, 1942) n. comb.
AB  - Pelecanema n. g. is erected for P. sirry (Khalil, 1931) n. comb., syn.
      Synhimantus sirry Khalil, 1931 (type-species) and P. pelecani (Johnston & Mawson,
      1942) n. comb., syn. Dispharynx pelecani Johnston & Mawson, 1942. In the
      structure of its cordons, consisting of two rows of delicate cuticular plates,
      the new genus is similar to Synhimantus Railliet, Henry & Sisoff, 1912,
      Dispharynx Railliet, Henry & Sisoff, 1912, Chordatortilis Machado de Mendonca &
      Olivera de Rodrigues, 1965 and Parachordatortilis Mutafchiev, Santoro & Georgiev,
      2010. Pelecanema sirry, a parasite of Pelecanus onocrotalus L. and P. crispus
      Bruch (Pelecaniformes, Pelecanidae) in Africa (Egypt and Senegal) and Europe
      (Ukraine and Bulgaria), is redescribed using light and scanning electron
      microscopy on the basis of specimens from P. crispus from Bulgaria. Pelecanema
      pelecani, a parasite of Pelecanus conspicillatus Temminck in Australia, is also
      redescribed using light microscopy on the basis of specimens from its type-host
      and type-locality. In contrast to a previous opinion recognising Pelecanema sirry
      and P. pelecani as synonyms, the two species are considered distinct and P.
      pelecani is validated.

PMID- 20700698
TI  - A revision of chiggers of the minuta species-group (Acari: Trombiculidae:
      Neotrombicula Hirst, 1925) using multivariate morphometrics.
AB  - We revise chiggers belonging to the minuta-species group (genus Neotrombicula
      Hirst, 1925) from the Palaearctic using size-free multivariate morphometrics.
      This approach allowed us to resolve several diagnostic problems. We show that the
      widely distributed Neotrombicula scrupulosa Kudryashova, 1993 forms three
      spatially and ecologically isolated groups different from each other in size or
      shape (morphometric property) only: specimens from the Caucasus are distinct from
      those from Asia in shape, whereas the Asian specimens from plains and mountains
      are different from each other in size. We developed a multivariate classification
      model to separate three closely related species: N. scrupulosa, N. lubrica
      Kudryashova, 1993 and N. minuta Schluger, 1966. This model is based on five shape
      variables selected from an initial 17 variables by a best subset analysis using a
      custom size-correction subroutine. The variable selection procedure slightly
      improved the predictive power of the model, suggesting that it not only removed
      redundancy but also reduced 'noise' in the dataset. The overall classification
      accuracy of this model is 96.2, 96.2 and 95.5%, as estimated by internal
      validation, external validation and jackknife statistics, respectively. Our
      analyses resulted in one new synonymy: N. dimidiata Stekolnikov, 1995 is
      considered to be a synonym of N. lubrica. Both N. scrupulosa and N. lubrica are
      recorded from new localities. A key to species of the minuta-group incorporating
      results from our multivariate analyses is presented.

PMID- 20700699
TI  - Systematic relationships of Mosgovoyia Spasskii, 1951 (Cestoda: Anoplocephalidae)
      and related genera inferred from mitochondrial and nuclear sequence data.
AB  - The present study evaluates the phylogenetic position and systematic
      relationships of two species of Mosgovoyia Spasskii, 1951 and related genera
      (Cestoda: Anoplocephalidae) based on sequences of 28S ribosomal RNA and
      mitochondrial NADH dehydrogenase subunit 1 (Nad1) genes. Both molecular data-sets
      show that M. pectinata (Goeze, 1782) and Schizorchis caballeroi Rausch, 1960 are
      sister species and that they are phylogenetically independent from M. ctenoides
      (Railliet, 1890). This shows unambiguously that Mosgovoyia [sensu Beveridge
      (1978)] is a non-monophyletic assemblage, supporting the validity of
      Neoctenotaenia Tenora, 1976, erected for M. ctenoides. The results also show that
      the morphologically related Ctenotaenia marmotae (Frohlich, 1802) is the sister
      species of Andrya rhopalocephala (Riehm, 1881) and therefore represents a more
      derived lineage. Modified diagnoses are provided for Mosgovoyia and
      Neoctenotaenia.

PMID- 20700700
TI  - Adoptive cellular therapy.
AB  - Cell-based therapies with various lymphocytes and antigen-presenting cells are
      promising approaches for cancer immunotherapy. The transfusion of T lymphocytes,
      also called adoptive cell therapy (ACT), is an effective treatment for viral
      infections, has induced regression of cancer in early stage clinical trials, and
      may be a particularly important and efficacious modality in the period following
      hematopoietic stem cell transplantation (HSCT). Immune reconstitution post-SCT is
      often slow and incomplete, which in turn leads to an increased risk of infection
      and may impact relapse risk in patients with malignant disease. Immunization post
      HSCT is frequently unsuccessful, due to the prolonged lymphopenia, especially of
      CD4 T cells, seen following transplant. ACT has the potential to enhance
      antitumor and overall immunity, and augment vaccine efficacy in the post
      transplant setting. The ability to genetically engineer lymphocyte subsets has
      the further potential to improve the natural immune response, correct impaired
      immunity, and redirect T cells to an antitumor effector response. This chapter
      focuses on various applications of ACT for cancer immunotherapy, and we discuss
      some of the latest progress and hurdles in translating these technologies to the
      clinic.

PMID- 20700701
TI  - TIM-3 and its regulatory role in immune responses.
AB  - T cell immunoglobulin mucin-(TIM)-3 was first identified as a molecule
      specifically expressed on IFN-gamma-secreting CD4(+) T helper 1 (Th1) and CD8(+)
      T cytotoxic (Tc1) cells in both mice and humans. TIM-3 acts as a negative
      regulator of Th1/Tc1 cell function by triggering cell death upon interaction with
      its ligand, galectin-9. This negative regulatory function of TIM-3 has now been
      expanded to include its involvement in establishing and/or maintaining a state of
      T cell dysfunction or "exhaustion" observed in chronic viral diseases. In
      addition, it is now appreciated that TIM-3 has other ligands and is expressed on
      other cell types, where it may function differently. Given that an increasing
      body of data support an important role for TIM-3 in both autoimmune and chronic
      inflammatory diseases in humans, deciphering the function of TIM-3 on different
      cell types during different immune conditions and how these can be regulated will
      be critical for harnessing the therapeutic potential of TIM-3 for the treatment
      of disease.

PMID- 20700702
TI  - Protein misfolding and cellular stress: an overview.
AB  - Cell survival and death are complex matters. Too much survival may lead to cancer
      and too much cell death may result in tissue degeneration. In this chapter, we
      will first of all focus on the cellular survival mechanisms that promote correct
      folding and maintenance of protein function. These mechanisms include protein
      quality control (PQC) systems comprising molecular chaperones and intracellular
      proteases in the cytosol, endoplasmatic reticulum (ER) and in the mitochondria.
      In addition to the PQC systems, mechanisms elicited by misfolded proteins, known
      as unfolded protein responses (UPRs), including induction/activation of
      antioxidant systems are also present in the three compartments of the cell.
      Second, we will discuss the mechanisms by which misfolded proteins lead to the
      generation of oxidative stress in the form of reactive oxygen species (ROS) and
      reactive nitrogen species (RNS). These species are produced mainly from
      superoxide (O2-) generated in the mitochondrial respiratory chain and from
      nitrogen oxide (NO) produced by the mitochondrial nitrogen oxide synthetase
      (mtNOS). Third, the effects of oxidative stress will be discussed, both with
      respect to mitochondrial dynamics, i.e., fission and fusion, and the related
      elimination of dysfunctional mitochondria by cellular cleaning systems, i.e.,
      mitophagy or mitoptosis, and related to the generation and cellular effects of
      oxidatively modified proteins, which closes a vicious cycle of protein misfolding
      and oxidative stress.

PMID- 20700703
TI  - Protein aggregation diseases: toxicity of soluble prefibrillar aggregates and
      their clinical significance.
AB  - Amyloid diseases, the most clinically relevant protein misfolding pathologies due
      to the high prevalence of some of them in the population, are characterized by
      the presence, in specific tissues and organs, of fibrillar deposits of specific
      peptides or proteins. Increasing efforts are presently dedicated at investigating
      the structural features and the structure-toxicity relation of the soluble
      oligomeric precursors arising in the path of fibril formation. In fact, it is
      increasingly recognised that these unstable, dynamic assemblies are remarkably
      toxic to cells thus featuring these as the main factor responsible for cell
      impairment in amyloid diseases. This chapter will review shortly the data
      presently available on the structural and biochemical features of these
      assemblies, as well as on their biological and clinical significance.

PMID- 20700704
TI  - Consequences of stress in the secretory pathway: The ER stress response and its
      role in the metabolic syndrome.
AB  - The unfolded protein response (UPR) was originally identified as a signaling
      network coordinating adaptive and apoptotic responses to accumulation of unfolded
      proteins in the endoplasmic reticulum (ER). More recent work has shown that UPR
      signaling can be triggered by a multitude of cellular events and that the UPR
      plays a critical role in the prevention, and also the progression, of a wide
      variety of diseases. Much attention has been paid to the role of the UPR in
      neurodegenerative diseases in the past. More recently, important roles for the
      UPR in diseases associated with the metabolic syndrome have been discovered. Here
      we review the role of the UPR in these diseases, including type 2 diabetes,
      atherosclerosis, fatty liver disease, and ischemia.

PMID- 20700705
TI  - What role does mitochondrial stress play in neurodegenerative diseases?
AB  - The essential need for mitochondrial function has been extensively shown to
      relate to neuronal health. Neurodegeneration and neurodegeneration-related
      diseases have been associated with multiple mitochondrial dysfunctions. This
      review highlights key findings related to commonly studied mitochondrial
      dysfunctions: imbalance of mitochondrial dynamics, mutations in the mitochondrial
      genome, excessive reactive oxygen species, and misfolded protein
      associations/interactions with the mitochondria. Future research in mitochondrial
      function will help elucidate complex neurodegenerative events while impacting
      both individual and societal health.

PMID- 20700706
TI  - Autophagy in disease.
AB  - Autophagy is a cellular quality control process by which cytoplasmic constituents
      including proteins, protein aggregates, organelles, and invading pathogens can be
      delivered to lysosomes for degradation. Autophagy is activated in response to
      changes in the internal status of the cell and/or changes in the extracellular
      environment. It is therefore essential for the maintenance of cellular
      homeostasis and for an efficient response to cellular stresses. As such autophagy
      has been implicated either in the pathogenesis, or response to a wide variety of
      diseases, bacterial, and viral infections, and ageing.

PMID- 20700707
TI  - Mitophagy and mitoptosis in disease processes.
AB  - Mitochondria play a very important role in cellular function, not only through
      key metabolic reactions and energy generation, but also by being a major site for
      production of reactive oxygen species and a key player in cell death. Therefore,
      mitochondrial dysfunction or damage may have severe consequences. Mitophagy
      (autophagic degradation of mitochondria) and mitoptosis (programmed destruction
      of mitochondria) are the processes by which cells can deal with impaired
      mitochondria. The efficiency of these processes may be a contributing factor to
      the pathogenesis of various diseases.

PMID- 20700708
TI  - Cellular stress and protein misfolding during aging.
AB  - Cells are under constant onslaught from several intrinsic and extrinsic
      stressors, which lead to the occurrence and accumulation of molecular damage,
      functional impairment, aging, and eventual death. Protein misfolding is both a
      cause and a consequence of increased cellular stress. An age-related failure of
      the complex systems for handling protein misfolding results in the accumulation
      of misfolded and aggregated proteins, and consequent conformational diseases.
      However, some misfolded proteins have been found to be both toxic and, in some
      cases, protective, highlighting the various complex, dynamic, and interdependent
      mechanisms at play. Molecular mechanisms are being elucidated for the occurrence
      of protein misfolding and for its prevention by chaperones and various pathways
      of degradation. Insights from the knowledge about proteodynamics are likely to
      impact future interventional strategies to counter stress and to promote healthy
      aging by preventing and/or treatment of protein conformational diseases.

PMID- 20700709
TI  - Measuring consequences of protein misfolding and cellular stress using OMICS
      techniques.
AB  - The ambition to measure all or at least a significant fraction of relevant
      molecules in a cell culture or tissue sample has reached possible realization
      with the development of the so-called OMICS technologies. We will here briefly
      review current technologies and give examples of their applications in
      investigations related to protein misfolding diseases. We will primarily cover
      the classical OMICS categories GENOMICS, TRANSCRIPTOMICS, METABOLOMICS, and with
      some more detail PROTEOMICS. These techniques are in most cases performed by
      dedicated core facilities or commercial services. We will give an assessment of
      uses as well as limitations of these technologies supported by examples of their
      application in research related to protein misfolding. We will further briefly
      discuss genome-wide RNA interference and finally touch on bioinformatics, because
      the huge amounts of data typically collected with OMICS techniques requires the
      application of specific software to handle and stratify the data sets. Today,
      most biologists using OMICS-techniques must, at least in part, be able to analyze
      their own data using user-friendly web-based tools.

PMID- 20700710
TI  - Production of cells with targeted integration of gene variants of human ABC
      transporter for stable and regulated expression using the Flp recombinase system.
AB  - The vector-mediated introduction of cDNA into mammalian cells by calcium
      phosphate co-precipitation or permeation with lipofectamine is widely used for
      the integration of cDNA into genomic DNA. Such integration, however, of cDNA
      occurs randomly at unpredictable sites in the host's chromosomal DNA, and the
      number of integrated recombinant DNAs is not controllable. To overcome this
      problem, we developed the Flp-In method to integrate one single copy of cDNA
      encoding the human ABC transporter ABCG2 into FRT-tagged genomic DNA. Examination
      of more than 20 metaphase spreads for both fluorescence in situ hybridization
      (FISH) mapping and multicolor-FISH analysis revealed that ABCG2 cDNA was
      incorporated into the telomeric region of the short arm on one of chromosomes 12
      in Flp-In-293 cells. By using those cells, we investigated the effect of genetic
      polymorphisms and post-translational modifications of human ABC transporter ABCG2
      on the protein expression and degradation. On the basis of our experience, it has
      been concluded that the Flp recombinase system provides a useful tool to
      quantitatively analyze the protein stability and endoplasmic reticulum (ER)
      associated degradation of proteins like the ABC transporter. This system is also
      applicable for similar studies of the biogenesis of other proteins using the
      secretory pathway as well as proteins with other cellular localizations.

PMID- 20700711
TI  - Stress response profiles in human fibroblasts exposed to heat shock or oxidative
      stress.
AB  - The upregulation of stress proteins is an important step in the cellular defense
      against various endogenous and exogenous stressors, and the stress response
      systems are therefore essential to cell maintenance and survival. In order to
      evaluate the cellular capability to cope with exogenous stressors, we
      investigated stress response profiles in cultured human fibroblasts exposed to
      short-term heat shock or oxidative stress. Quantitative PCR analysis as well as
      Western blotting demonstrated a specific upregulation of Hsp70 mRNA and protein
      after heat shock, while heme oxygenase 1 (HO1 or Hsp32) mRNA and protein was
      specifically upregulated following H2O2-induced oxidative stress. Hsp70 and HO1
      should therefore be considered as useful biomarkers for acute heat stress and
      oxidative stress, respectively. Moreover, the results indicate that the
      expression of Hsp70 and HO1 in response to exogenous stressors may be regulated
      through different mechanisms.

PMID- 20700712
TI  - Examining ubiquitinated protein aggregates in tissue sections.
AB  - In the cell, the binding of ubiquitin to abnormal or misfolded proteins marks
      them for degradation by the proteasome or lysosome via autophagy. Ubiquitinated
      protein aggregates form when an increase in protein misfolding exceeds the
      degradation capacity of the cell. Many cellular stresses can cause an increase in
      the amount of ubiquitinated misfolded protein and failure to eliminate these
      proteins can disrupt cellular homeostasis and cause cellular toxicity.
      Ubiquitinated-protein aggregates accumulate in the cytosol and can be detected in
      tissues of patients with a variety of diseases, including Alzheimer's,
      Parkinson's, and Huntington's. Using a diabetic rat model, we have shown that
      ubiquitinated-protein aggregates form in pancreatic beta cells during diabetes
      induced oxidative stress. Aggregates were also evident in the hippocampus,
      kidney, and liver of these animals. Our detailed protocol is provided here.
      Mounted tissue sections were first deparaffinized, then boiled in sodium citrate
      buffer to expose the antigen, followed by a specific staining procedure that
      allows for detection of ubiquitinated-protein aggregates. The ability to
      visualize ubiquitinated-protein aggregates in tissue sections can provide further
      understanding of the pathobiology of diseases associated with misfolded protein.

PMID- 20700713
TI  - Determination of proteasomal activities.
AB  - The proteasome is an important component of the intracellular system for the
      turnover of proteins. The mammalian proteasome is engaged to degrade a bulky
      fraction of soluble intracellular proteins both in an ubiquitin-dependent and
      independent manner. The proteasome is composed by a central catalytic core--the
      20S proteasome--where three different proteases are located, whose activities can
      be measured. A detailed protocol for measuring accurately the three activities of
      the 20S proteasome in cell and tissue homogenates, using specific fluorogenic
      substrates and a microplate reader fluorometer, are described. Successful
      applications of this method include determining changes in the proteasomal
      activities during aging, anti-aging interventions, cell cycle analysis, and in
      various disease states including neurodegenerative diseases and cancers.

PMID- 20700714
TI  - Measurement of autophagy in cells and tissues.
AB  - Two major proteolysis systems, the ubiquitin-proteasome system, and the autophagy
      lysosome system, contribute to degradation of various types of protein and/or
      protein aggregates. In general, the autophagy-lysosome system is involved in bulk
      intracellular degradation of proteins and organelles, while the ubiquitin
      proteasome system is selective. During autophagy, a cytosolic form of LC3 (LC3-I)
      is conjugated to phosphatidylethanolamine to form LC3-phosphatidylethanolamine
      conjugate (LC3-II), which is recruited to autophagosomal membranes, and LC3-II is
      degraded by lysosomal hydrolases after the fusion of autophagosomes with
      lysosomes. Therefore, lysosomal turnover of LC3-II reflects starvation-induced
      autophagic activity, and detection of LC3 by immunoblotting or immunofluorescence
      has become a reliable method for monitoring autophagy. When autophagy is
      impaired, the level of p62/SQSTM1, a ubiquitin- and LC3-binding protein, is
      increased in addition to the accumulation of ubiquitinated proteins. Here, we
      describe basic protocols to analyze endogenous LC3-II, p62, and autophagy-related
      proteins by immunoblotting, immunofluorescence, and electron microscopy.

PMID- 20700715
TI  - Transcription factor sequestration by polyglutamine proteins.
AB  - In polyglutamine diseases including Huntington's disease, the causative gene
      products containing expanded polyglutamine form nuclear aggregates in neurons.
      Recent studies have identified several transcriptional factors, which interact
      with and are sequestered by expanded polyglutamine aggregates in neurons.
      Further, altered expression of many genes has been shown in several polyglutamine
      disease models. These observations suggest an involvement of transcriptional
      dysregulation in pathological process of these diseases. In this chapter, we
      introduce several methods to examine the interaction of transcriptional factors
      with and their sequestration by expanded polyglutamine proteins in vitro and in
      vivo.

PMID- 20700716
TI  - Biological membranes as protein aggregation matrices and targets of amyloid
      toxicity.
AB  - Aberrantly folded proteins and peptides are hallmarks of amyloid diseases. A
      deeper knowledge of the pathways leading to the formation of amyloid protein
      aggregates and of the mechanisms of their cytotoxicity is fundamental for a
      better understanding of several human diseases with amyloid deposition.
      Increasing evidence indicates that amyloids arising from different peptides and
      proteins behave similarly as for their cytotoxic effects. In general, different
      cell susceptibility to toxic protein aggregates depends on the efficiency of
      different cell types to accumulate amyloid precursors at their plasma membrane
      with subsequent growth of pre-fibrillar and fibrillar entities, resulting in
      membrane perturbation and cell damage. Actually, protein-lipid interaction
      displays a twofold aspect: on the one hand, the presence of a lipid membrane may
      influence protein unfolding and the aggregation process; on the other hand,
      protein aggregates may modify membrane structure and permeability. Understanding
      the molecular basis of the membrane-protein interaction (but, more extensively,
      of the surface-protein interaction) may help elucidating some of the factors
      affecting protein misfolding and aggregation in vivo. This topic has been
      investigated by a variety of techniques such as atomic force microscopy,
      transmission electron microscopy, confocal laser microscopy and flow cytometric
      analysis. In this overview, such techniques will be reviewed with special
      emphasis to their use in protein aggregation studies.

PMID- 20700717
TI  - Measurement of mitochondrial ROS production.
AB  - The significance of reactive oxygen species (ROS) as aggravating or primary
      factors in numerous pathologies is widely recognized, with mitochondria being
      considered the major intracellular source of ROS. It is not yet possible to
      routinely measure mitochondrial ROS in animals or cultured cells with a
      reasonable degree of certainty. However, at the level of isolated mitochondria,
      one can easily monitor and quantify the rate of ROS production, identify major
      sites of ROS production, and compare the rates of ROS production in mitochondria
      isolated from normal and diseased tissue. In this chapter, we describe in detail
      the most recent and reliable method to measure mitochondrial ROS as the rate of
      H2O2 emission. This method may be employed with minimal modifications to measure
      H2O2 production by mitochondria isolated from various tissues and under a wide
      variety of experimental conditions.

PMID- 20700718
TI  - In vivo detection of oxidized proteins: a practical approach to tissue-derived
      mitochondria.
AB  - Mitochondria are the major producers of free radical oxygen species (ROS) as well
      as the major target of oxidative damage. Defects in the mitochondrial respiratory
      chain complexes can increase ROS production and reduce ROS removal, leading to
      oxidative modification of proteins, lipids, and DNA. AAA proteases of the inner
      mitochondrial membrane, paraplegin and AFG3L2, participate in the biogenesis and
      maintenance of respiratory chain complexes. These proteins form hetero-oligomeric
      paraplegin/AFG3L2 and homo-oligomeric AFG3L2 complexes named m-AAA proteases.
      Inactivation of m-AAA proteases causes respiratory defects and altered
      mitochondrial morphology both in yeast and in mammals. In fact, mouse models
      defective for Afg3l2 display a very severe neurological syndrome and die within
      two weeks after birth. They display widespread morphological alterations of
      mitochondria in the central and peripheral nervous system and deficiencies in
      respiratory chain complex I and in complex III, which are major producers of ROS
      in physiological and especially in pathological conditions. Therefore, an
      efficient and reliable methodology to monitor the effect of increased ROS
      production is useful for accurately phenotyping cellular and animal models
      mutants in m-AAA. By measuring carbonyl formation as marker of protein oxidation,
      we have shown that respiratory defects cause oxidative damage in Afg3l2 mutants,
      indicating that oxidative stress is crucial in the pathogenesis of m-AAA
      deficiency.

PMID- 20700719
TI  - Measurement of oxidized/reduced glutathione ratio.
AB  - Glutathione (GSH) is the most abundant antioxidant in aerobic cells, present in
      micromolar (microM)-concentrations in bodily fluids and in millimolar (mM)
      concentrations in tissue. GSH is critical for protecting the brain from oxidative
      stress, acting as a free radical scavenger and inhibitor of lipid peroxidation.
      GSH also participates in the detoxification of hydrogen peroxide by various
      glutathione peroxidases. The ratio of reduced GSH to oxidized GSH (GSSG) is an
      indicator of cellular health, with reduced GSH constituting up to 98% of cellular
      GSH under normal conditions. However, the GSH/GSSG ratio is reduced in
      neurodegenerative diseases, such as Parkinson's disease (PD) and Alzheimer's
      disease (AD). Measuring the GSH/GSSG ratio in pathological tissues and
      experimental models thereof in comparison to the results in controls is an
      excellent way to assess potential therapeutics efficacy in maintaining cellular
      redox potential. The availability of UV/Visible instruments equipped with 96-well
      plate readers as common laboratory equipment has made measuring the GSH/GSSG
      ratio on multiple samples a manageable procedure.

PMID- 20700720
TI  - Determination of altered mitochondria ultrastructure by electron microscopy.
AB  - Mitochondria play a number of important roles, including production of ATP for
      the generation of energy, involvement in the regulation of excitotoxicity,
      involvement in the homeostasis of intracellular Ca2+, production of reactive
      oxygen species, and the release of cytochrome c, a potent trigger of programmed
      cell death (apoptosis). Mitochondrial dysfunction has long been implicated in the
      pathogenesis of neurodegenerative disorders such as Parkinson's disease and
      amyotrophic lateral sclerosis (ALS), and in physiological conditions such as
      aging. Mitochondrial dysfunction has also been associated with endoplasmic
      reticulum (ER) stress caused by the accumulation of misfolded or unfolded
      proteins due to decreased ER-associated degradation (ERAD), by which misfolded or
      unfolded proteins are transported from the lumen of the ER to the cytoplasm,
      where they are ubiquitinated and eventually eliminated. The mitochondria may
      undergo various morphological alterations reflective of different pathological
      conditions and diseases. The transmission electron microscope (TEM) remains a
      powerful tool for the morphological examination of mitochondria and is expected
      to continue to enhance our understanding of cellular functions and dysfunction.
      Moreover, electron microscopic study has enabled us to confirm mitochondrial
      involvement in the pathomechanism of certain neurodegenerative diseases. Here,
      electron-microscopy procedures are outlined with particular emphasis on some
      practical aspects of this approach. Electron-micrographs of mitochondrial
      alterations under various normal and pathological conditions are provided,
      including images from human control individuals, patients with ALS, and familial
      ALS-related mutant SOD1 (G93A and H46R) transgenic mice.

PMID- 20700721
TI  - Assessing Bad sub-cellular localization under conditions associated with
      prevention or promotion of mitochondrial permeability transition-dependent
      toxicity.
AB  - Cells belonging to the monocyte/macrophage lineage are in general highly
      resistant to peroxynitrite, a reactive nitrogen species extensively produced by
      these and other cell types under inflammatory conditions. Resistance is not
      dependent on the scavenging of peroxynitrite but is rather associated with the
      prompt activation of a survival signaling in response to various molecules
      largely available at the inflammatory sites, as arachidonic acid and products of
      the 5-lipoxygenase or cyclooxygenase pathways. We detected significant levels of
      Bad in the mitochondria of monocytes/macrophages and found that these signaling
      pathways converge in Bad phosphorylation, and thus in its cytosolic accumulation.
      Phosphorylation inhibits binding of Bad to Bcl-2, or BclXL, and promotes its
      translocation to the cytosol, thereby enabling Bcl-2 and BclXL to exert effects
      leading to prevention of mitochondrial permeability- transition (MPT). Upstream
      inhibition of the survival signaling indeed promotes the mitochondrial
      accumulation of Bad and the rapid onset of MPT-dependent toxicity. The above
      results contribute to the definition of the mechanism(s) whereby
      monocytes/macrophages survive to peroxynitrite in inflamed tissues.

PMID- 20700722
TI  - A cellular viability assay to monitor drug toxicity.
AB  - A central part of the research in protein misfolding and its associated disorders
      is the development of treatment strategies based on ensuring cellular protein
      homeostasis. This often includes testing chemical substances or drugs for their
      ability to counteract protein misfolding processes and to promote correct
      folding. Such investigations also include assessment of how the tested chemical
      substances affect cellular viability, that is, their cytotoxic effect.
      Investigations of cytotoxicity often require testing several different
      concentrations and drug exposure times using cells in culture. It is therefore
      attractive to use a viability test that permits the analysis of many samples with
      little handling time. This protocol describes a simple and fast methodology to
      analyze viability of lymphoblastoid cells and to test putative cytotoxic effects
      associated with exposure to a chemical substance, here exemplified by celastrol.
      The natural substance celastrol has been used for many years in traditional
      Chinese medicine and has subsequently been shown to induce transcription of genes
      encoding molecular chaperones (heat shock proteins) that are involved in
      promoting folding of cellular proteins. The well-described colorimetric
      tetrazolium salt (MTT) assay, which monitors metabolic activity of cultured
      cells, was adapted to analyze the viability of cells exposed to celastrol. After
      having established a suitable cell seeding density, the dose-dependence and time
      course of viability reduction of lymphoblastoid cells treated with celastrol were
      determined. It was found that 4- and 24-h exposure to 0.8 microM celastrol
      reduced the viability of lymphoblastoid cells, with the most severe effect
      observed at 24 h with MTT reductions approaching 30% of non-exposed cells. For a
      series of incubations for 24 h, it was found that concentrations as low as 0.2
      microM were sufficient to affect the viability, and celastrol concentrations of
      0.5 microM reduced the MTT reduction rate to approximately half the level
      displayed by cells receiving vehicle alone.

PMID- 20700723
TI  - Rescue of misfolded proteins and stabilization by small molecules.
AB  - Increasing stability of functional proteins by binding small compounds and ions
      has long been used to extend shelf-life of protein formulations in the
      pharmacological and biotechnological industry. Likewise, the therapeutic
      application of small molecules for in vivo recovery and maintenance of structure
      and function of proteins is steadily increasing. Compounds that can rescue
      misfolded proteins by stimulating their correct folding and/or the stabilization
      of native-like conformations in vivo are referred to as pharmacological
      chaperones. Here we present thermal-shift and isothermal methods for the high
      throughput screening of stabilizing pharmacological chaperones for soluble and
      membrane proteins. The effect of selected hit compounds on the kinetics of
      protein synthesis is further evaluated by an in vitro transcription-translation
      rapid translation system. These procedures can be integrated in an
      interdisciplinary and translational approach for the search of personalized
      pharmacological chaperones in genetic misfolding diseases.

PMID- 20700724
TI  - Mitochondria as integrators of signal transduction and energy production in
      cardiac physiology and disease.
AB  - Fascinating links are beginning to be discovered between mitochondrial function
      and cardiac physiology and disease in the context of diverse signaling
      mechanisms, energy production, and intersection with pathways producing reactive
      oxygen species. Proteins long known to drive mitochondrial fusion and fission are
      now reported to have emergent functions in intracellular calcium homeostasis,
      apoptosis, and vascular smooth muscle cell proliferation, all key issues in
      cardiac disease. Moreover, mitochondrial fusion has been demonstrated to be
      required for normal myofibril organization in skeletal muscle, and decreasing
      fission may confer protection against ischemic heart disease. These processes
      broaden the traditional role in energy production undertaken by mitochondria and
      provide new directions for potential therapeutic leads.

PMID- 20700725
TI  - Targeting the epidermal growth factor receptor (HER) family by T cell receptor
      gene-modified T lymphocytes.
AB  - Human epidermal growth factor receptor 2 (HER2) has been successfully targeted as
      a breast cancer-associated antigen by various strategies. HER2 is also
      overexpressed in other solid tumors such as stomach cancer, as well as in
      hematological malignancies such as acute lymphoblastic leukemia. HER2-targeted
      therapies are currently under clinical investigation for a panel of malignancies.
      In this study, we isolated the T cell receptor (TCR) genes of a HER2-reactive
      allo-human leukocyte antigen-A2-restricted CTL clone and introduced the TCRalpha-
      and beta-chain genes into the retrovirus vector MP71. Murinization and codon
      optimization of the HER2-reactive TCR was required for efficient TCR expression
      in primary human T cells. The tumor recognition efficiency of HER2-TCR gene
      modified T cells was similar to the parental CTL clone from which the TCR genes
      were isolated. The known cross-reactivity of the HER2-reactive TCR with HER3 and
      HER4 was retained when the TCR was transduced into primary T cells. Our results
      could contribute to the development of a TCR-based approach for the treatment of
      HER2-positive breast cancer, as well as of other malignancies expressing HER2,
      HER3, and/or HER4.

PMID- 20700726
TI  - Crisis resolution/home treatment team workers' understandings of the concept of
      crisis.
AB  - BACKGROUND: The crisis resolution/home treatment (CR/HT) model has brought
      significant reform of acute mental health care in the UK and beyond. The complex
      issue of conceptualising crisis is, however, overlooked in CR/HT literature. This
      study aimed to investigate how crisis is understood amongst those working in
      CR/HT teams. METHOD: Framework analysis was applied to semi-structured interviews
      with 39 CR/HT workers representative of multidisciplinary mix and drawn from four
      different teams. RESULTS: Whilst there was an acknowledgment of the concept's
      complex nature, there was consensus in: respondents' characterising of crisis;
      about three different presenting clinical patterns ('clusters') encountered in
      CR/HT work; and, the pattern of the crisis phenomenon over time. CONCLUSIONS: The
      findings suggest further development of the CR/HT model, including improving
      conceptual clarity (to benefit communication with referrers and judge clinical
      outcome), better timed intervention, and varying intervention for different
      clusters of crisis presentation.

PMID- 20700727
TI  - Use of Surgisis mesh in the management of polypropylene mesh erosion into the
      vagina.
AB  - INTRODUCTION AND HYPOTHESIS: mesh in pelvic reconstructive surgery is being used
      increasingly in clinical practice. Complications such as mesh erosion and
      dyspareunia can cause significant patient morbidity. In cases where vaginal mesh
      erosions are large or multifocal resulting in inadequate healthy epithelium for
      repair, this may lead to recurrent mesh erosion or vaginal stenosis. METHOD: nine
      patients with synthetic mesh erosion who failed to respond to conservative
      measures were managed surgically with Surgisis. RESULTS: the median time at which
      patients presented with mesh erosion was 12 weeks. The size of erosion ranged
      from 1 to 4 cm in diameter. At follow-up, five patients were cured, three still
      had evidence of mesh erosion although the overall defects were smaller, and one
      patient required further surgery. CONCLUSION: with mesh erosion being a
      troublesome reality following insertion of synthetic mesh repairs, Surgisis may
      prove to be a useful option in the treatment of large vaginal mesh defects.

PMID- 20700728
TI  - Interobserver and interdisciplinary reproducibility of 3D endovaginal ultrasound
      assessment of pelvic floor anatomy.
AB  - INTRODUCTION AND HYPOTHESIS: the study aims were to evaluate (1) the
      interobserver and (2) the interdisciplinary repeatability of levator hiatus,
      urethral thickness, and anorectal angle measurements using three-dimensional
      endovaginal ultrasound (3D-EVUS). METHODS: twenty-seven nulliparous asymptomatic
      females were imaged with 3D-EVUS. Analyses were conducted off-line from stored 3D
      volumes by six readers (two radiologists, two urogynecologists, and two
      colorectal surgeons) using a standardized technique. Reproducibility was
      determined using the interclass correlation coefficients (ICC). RESULTS: the
      overall interobserver repeatability for levator hiatus dimensions was good to
      excellent (ICC, 0.655-0.889), for urethral thickness was good (ICC, 0.624), and
      for anorectal angle was moderate (ICC, 0472). The interdisciplinary repeatability
      for levator hiatus indices was good to excellent (ICC, 0.639-0.915), for urethral
      thickness was moderate to good (ICC, 0.565-0.671), and for anorectal angle was
      fair to moderate (ICC, 0.204-0.434). CONCLUSIONS: 3D-EVUS yields reproducible
      measurements of levator hiatus dimensions and urethral thickness in asymptomatic
      nulliparous women.

PMID- 20700729
TI  - Obstetric fistula: the ECWA Evangel VVF Center surgical experience from Jos,
      Nigeria.
AB  - INTRODUCTION AND HYPOTHESIS: The objectives of this study are to analyze the
      surgical outcomes of women undergoing obstetric fistula repair operations at the
      ECWA Evangel VVF Center, Jos, Nigeria, and to identify factors associated with
      postoperative urinary continence. METHODS: Sociodemographic and clinical data
      were abstracted retrospectively from the Center's database for patients who
      underwent vesicovaginal fistula (VVF) repair operations. These data were compared
      with clinical outcome ("wet" or "dry") at the time of hospital discharge.
      RESULTS: From August 1998 to April 2004, 1,084 fistula repair operations were
      performed on 926 patients. A vaginal approach was used in 90.1% of cases, and
      postsurgical continence was achieved in 70.5% of patients. Continence was more
      likely in patients with an intact urethra, an upper or midvaginal fistula, and
      less fibrosis than in those patients who remained wet. CONCLUSIONS: Two thirds of
      patients with obstetric fistulas can be cured, with complete restoration of
      continence and low surgical morbidity, using a transvaginal surgical approach.

PMID- 20700730
TI  - Microarray analysis of differentially expressed genes in vaginal tissues in
      postmenopausal women. The role of stress urinary incontinence.
AB  - INTRODUCTION AND HYPOTHESIS: This study aimed to explore gene expression and
      their regulatory mechanisms in etiology of stress urinary incontinence (SUI).
      METHODS: Tissue samples were taken from the paraurethral vaginal wall from three
      pairs of postmenopausal, age/body mass index/parity-matched SUI, and continent
      women and subjected to microarray analysis using the Affymetrix GeneChip(r) Human
      Genome U133 Plus 2.0 oligonucleotide chip set. The significantly differentially
      expressed genes and their protein expression were confirmed by quantitative PCR
      and Western blot. RESULTS: Seventy-five differentially expressed genes were
      listed; 31 genes were upregulated in SUI group, while 44 were downregulated. Gene
      metabolic pathway analysis showed that solutable N-ethylmaleimide-sensitive
      factor attachment protein receptor signaling pathway and neurodegenerative
      disorder pathway were the most predominant. CONCLUSIONS: Apolipoprotein E, growth
      factor receptor-bound protein 2, Golgi SNAP receptor complex member 1, and
      glucosidase, beta, acid may play a neurodegenerative role in SUI development.

PMID- 20700731
TI  - Eyeblink entrainment at breakpoints of speech.
AB  - The eyes play an essential role in social communication. Eyeblinks, however, have
      thus far received minor attention. We previously showed that subjects blink in
      synchrony while viewing the same video stories (Nakano et al. in Proc R Soc B
      276:3635-3644, 2009). We therefore hypothesized that eyeblinks are synchronized
      between listener and speaker in face-to-face conversation. Here, we show that
      listeners blinked with a delay of 0.25-0.5 s after the speaker blinked when the
      listeners viewed close-up video clips (with sound) of the speaker's face.
      Furthermore, this entrainment was selectively triggered by speaker's eyeblinks
      occurring at the end and during pauses in speech. Eyeblink entrainment was not
      observed when viewing identical video clips without sound, indicating that blink
      entrainment was not an automatic imitation. We therefore suggest that eyeblink
      entrainment reflects smooth communication between interactants.

PMID- 20700732
TI  - Variant and invariant patterns embedded in human locomotion through whole body
      kinematic coordination.
AB  - Step length, cadence and joint flexion all increase in response to increases in
      gradient and walking speed. However, the tuning strategy leading to these changes
      has not been elucidated. One characteristic of joint variation that occurs during
      walking is the close relationship among the joints. This property reduces the
      number of degrees of freedom and seems to be a key issue in discussing the tuning
      strategy. This correlation has been analyzed for the lower limbs, but the
      relation between the trunk and lower body is generally ignored. Two questions
      about posture during walking are discussed in this paper: (1) whether there is a
      low-dimensional restriction that determines walking posture, which depends not
      just on the lower limbs but on the whole body, including the trunk and (2)
      whether some simple rules appear in different walking conditions. To investigate
      the correlation, singular value decomposition was applied to a measured walking
      pattern. This showed that the whole movement can be described by a closed loop on
      a two-dimensional plane in joint space. Furthermore, by investigating the effect
      of the walking condition on the decomposed patterns, the position and the tilt of
      the constraint plane was found to change significantly, while the loop pattern on
      the constraint plane was shown to be robust. This result indicates that humans
      select only certain kinematic characteristics for adapting to various walking
      conditions.

PMID- 20700733
TI  - Numbers can move our hands: a spatial representation effect in digits
      handwriting.
AB  - The interaction between numbers and action-related processes is currently one of
      the most investigated topics in numerical cognition. The present study
      contributes to this line of research by investigating, for the first time, the
      effects of number on an overlearned complex motor plan that does not require
      explicit lateralised movements or strict spatial constrains: spontaneous
      handwriting. In particular, we investigated whether the spatial mapping of
      numbers interferes with the motor planning involved in writing. To this aim,
      participants' spontaneous handwriting of single digits (Exp. 1) and letters (Exp.
      2) was recorded with a digitising tablet. We show that the writing of numbers is
      characterised by a spatial dislocation of the digits as a function of their
      magnitude, i.e., small numbers were written leftwards relative to large numbers.
      In contrast, the writing of letters showed a null or marginal effect with respect
      to their dislocation on the writing area. These findings show that the automatic
      mapping of numbers into space interacts with action planning by modulating
      specific motor parameters in spontaneous handwriting.

PMID- 20700734
TI  - Mutation biases and mutation rate variation around very short human
      microsatellites revealed by human-chimpanzee-orangutan genomic sequence
      alignments.
AB  - I have studied mutation patterns around very short microsatellites, focusing
      mainly on sequences carrying only two repeat units. By using human-chimpanzee
      orangutan alignments, inferences can be made about both the relative rates of
      mutations and which bases have mutated. I find remarkable non-randomness, with
      mutation rate depending on a base's position relative to the microsatellite, the
      identity of the base itself and the motif in the microsatellite. Comparing the
      patterns around AC2 with those around other four-base combinations reveals that
      AC2 does not stand out as being special in the sense that non-repetitive
      tetramers also generate strong mutation biases. However, comparing AC2 and AC3
      with AC4 reveals a step change in both the rate and nature of mutations
      occurring, suggesting a transition state, AC4 exhibiting an alternating high-low
      mutation rate pattern consistent with the sequence patterning seen around longer
      microsatellites. Surprisingly, most changes in repeat number occur through base
      substitutions rather than slippage, and the relative probability of gaining
      versus losing a repeat in this way varies greatly with repeat number. Slippage
      mutations reveal rather similar patterns of mutability compared with point
      mutations, being rare at two repeats where most cause the loss of a repeat, with
      both mutation rate and the proportion of expansion mutations increasing up to 6-8
      repeats. Inferences about longer repeat tracts are hampered by uncertainties
      about the proportion of multi-species alignments that fail due to multi-repeat
      mutations and other rearrangements.

PMID- 20700735
TI  - Actin gene family dynamics in cryptomonads and red algae.
AB  - Here we present evidence for a complex evolutionary history of actin genes in red
      algae and cryptomonads, a group that acquired photosynthesis secondarily through
      the engulfment of a red algal endosymbiont. Four actin genes were found in the
      nuclear genome of the cryptomonad, Guillardia theta, and in the genome of the red
      alga, Galdieria sulphuraria, a member of the Cyanidiophytina. Phylogenetic
      analyses reveal that the both organisms possess two distinct sequence types,
      designated "type-1" and "type-2." A weak but consistent phylogenetic affinity
      between the cryptomonad type-2 sequences and the type-2 sequences of G.
      sulphuraria and red algae belonging to the Rhodophytina was observed. This is
      consistent with the possibility that the cryptomonad type-2 sequences are derived
      from the red algal endosymbiont that gave rise to the cryptomonad nucleomorph and
      plastid. Red algae as a whole possess two very different actin sequence types,
      with G. sulphuraria being the only organism thus far known to possess both. The
      common ancestor of Rhodophytina and Cyanidiophytina may have had two actin genes,
      with differential loss explaining the distribution of these genes in modern-day
      groups. Our study provides new insight into the evolution and divergence of actin
      genes in cryptomonads and red algae, and in doing so underscores the challenges
      associated with heterogeneity in actin sequence evolution and ortholog/paralog
      detection.

PMID- 20700736
TI  - Rhinosporidiosis isolated to the distal clavicle: a rare presentation
      clinicoradiologically mimicking a bone tumor.
AB  - Rhinosporidiosis is a chronic granulomatous disease caused by Rhinosporidium
      seeberi, which commonly affects young men and predominantly involves the mucous
      membranes of the nose, nasopharynx and eyes. Involvement of extranasal sites
      including bone has been reported, but rarely. We present a case of a 32-year-old
      farmer, who presented with a non-tender, fixed swelling over his right shoulder.
      Radiography and CT imaging showed an expansile, lytic, destructive lesion
      involving the lateral end of the right clavicle with soft tissue extension. The
      clinicoradiological impression was that of a primary bone tumor. Biopsy and wide
      excision of the lesion revealed features of rhinosporidiosis. There were no
      mucocutaneous lesions. Involvement of bone without associated mucocutaneous
      lesions is exceedingly rare in rhinosporidiosis. Involvement of the clavicle, as
      seen in the present case, has not been reported in the English language-peer
      reviewed literature, to the best of our knowledge.

PMID- 20700737
TI  - FDG-PET/CT in infections: the imaging method of choice?

PMID- 20700738
TI  - FDG PET/CT for monitoring response to neoadjuvant chemotherapy in breast cancer
      patients.

PMID- 20700739
TI  - Current status of sentinel lymph-node biopsy in patients with breast cancer.
AB  - Axillary node status is the most important prognostic indicator for patients with
      invasive breast cancer. Sentinel lymph-node biopsy (SLNB) is widely accepted and
      the preferred procedure for identifying lymph-node metastasis. SLNB allows
      focused excision and pathological examination of the most likely axillary lymph
      nodes to receive tumor metastases while avoiding morbidities associated with
      complete axillary nodal dissection. Since its introduction in the early 1990s,
      the process of SLNB has undergone continual modification and refinement; however,
      the procedure varies between institutions and controversies remain. In this
      review, we examine the technical issues that influence the success of lymph node
      mapping, discuss the controversies, and summarize the indications and
      contraindications for axillary node mapping and biopsy in clinical practice.

PMID- 20700741
TI  - The bishop and anatomist Niels Stensen (1638-1686) and his contributions to our
      early understanding of the brain.
AB  - Many physicians are familiar with the parotid duct and the Danish
      physician/anatomist's name associated with it. However, most are unaware of Niels
      Stensen's life and his significant contributions to the early study of the brain.
      This physician of the Medici court was clearly ahead of his time and found errors
      in the publications of such giants as Varolius and Willis. The present review
      discusses the life of this seventeenth century anatomist, physician, and
      priest/bishop and highlights his contributions to neuroanatomy.

PMID- 20700740
TI  - Phase II study of docetaxel, capecitabine, and cisplatin as neoadjuvant
      chemotherapy for locally advanced breast cancer.
AB  - PURPOSE: Docetaxel, capecitabine, and cisplatin are effective chemotherapeutic
      agents for breast cancer with significant synergistic cytotoxicity demonstrated
      by in vitro studies. The purpose of this study was to assess the efficacy of a
      combination of docetaxel, capecitabine, and cisplatin (TXP) in patients diagnosed
      with locally advanced breast cancer (LABC). METHODS: Patients (n = 42) with
      chemotherapy-naive LABC (stage IIIa or IIIb) were enrolled. The chemotherapeutic
      regimen consisted of 4-6 cycles of intravenous docetaxel (60 mg/m(2)) and
      cisplatin (50 mg/m(2)) on day 1, plus oral capecitabine (1,800 mg/m(2)/day) on
      day 1-14, repeated every 3 weeks. Upon completion of therapy, the primary tumor
      was resected when not contraindicated. RESULTS: Median patient age was 48.5 years
      (range 31-66 years). Median tumor size was 6.8 cm (range 2.7-15 cm), 29 patients
      were node-positive, and 12 patients were hormone receptor positive. A total of
      216 cycles (median 5; range 3-6 cycles) were administered without prophylactic G
      CSF. The predominant toxicities were grade 3/4 neutropenia (30%/28%) and no grade
      3/4 thrombocytopenia, febrile neutropenia, or grade 4 non-hematological
      toxicities were observed. Grade 3 non-hematological toxicities included hand-foot
      syndrome (5.6%) and vomiting (0.5%). The overall clinical response rate was 97.6%
      (41/42). Six of the 42 patients (14.3%) achieved a complete pathological
      response. Of 22 patients who completed 6 cycles of combination treatment, the
      complete pathological response was 27.3% (6/22). CONCLUSIONS: A combination of
      TXP can be administered safely without prophylactic G-CSF, and appears to be an
      effective neoadjuvant regimen in patients with LABC.

PMID- 20700742
TI  - Three-dimensional power Doppler study of changes in uterine vascularity after
      absorbable cervical tourniquet during open myomectomy.
AB  - OBJECTIVE: To evaluate the effect of an absorbable polyglactin tie (i.e.,
      cervical tourniquet) on postoperative uterine artery blood flow using three
      dimensional (3D) power Doppler. PATIENTS AND METHODS: Forty-four patients with
      symptomatic uterine myomas warranting surgical treatment were randomized to
      either receive absorbable cervical tourniquets group 1 or not group 2. Resistance
      index, pulsatility index, and peak systolic velocity of the uterine artery as
      well as 3D power Doppler study of uterine vascularity in terms of VI, FI,
      vascularization flow index (VFI) were performed preoperatively and at 1 and 3
      months, postoperatively. Estimated myoma and uterine volume, operative time were
      compared in both groups. RESULTS: No significant difference in the
      characteristics of myomas, regarding number, size, and location of the largest
      myoma, between the two studied groups. No significant differences between the two
      groups for uterine artery RIs, PIs, and PSV at 1 and 3 months, postoperatively.
      The myometrial VI, FI and VFI in the study group were comparable to those in the
      control group. No sequential change in FI was noted in either group. CONCLUSION:
      Absorbable cervical tourniquet during open myomectomy did not compromise uterine
      perfusion as evaluated by 3D power Doppler study.

PMID- 20700744
TI  - Sustained enhancement of photosynthesis in mature deciduous forest trees after 8
      years of free air CO(2) enrichment.
AB  - Carbon uptake by forests constitutes half of the planet's terrestrial net primary
      production; therefore, photosynthetic responses of trees to rising atmospheric
      CO(2) are critical to understanding the future global carbon cycle. At the Swiss
      Canopy Crane, we investigated gas exchange characteristics and leaf traits in
      five deciduous tree species during their eighth growing season under free air
      carbon dioxide enrichment in a 35-m tall, ca. 100-year-old mixed forest. Net
      photosynthesis of upper-canopy foliage was 48% (July) and 42% (September) higher
      in CO(2)-enriched trees and showed no sign of down-regulation. Elevated CO(2) had
      no effect on carboxylation efficiency (V (cmax)) or maximal electron transport (J
      (max)) driving ribulose-1,5-bisphosphate (RuBP) regeneration. CO(2) enrichment
      improved nitrogen use efficiency, but did not affect leaf nitrogen (N)
      concentration, leaf thickness or specific leaf area except for one species. Non
      structural carbohydrates accumulated more strongly in leaves grown under elevated
      CO(2) (largely driven by Quercus). Because leaf area index did not change, the
      CO(2)-driven stimulation of photosynthesis in these trees may persist in the
      upper canopy under future atmospheric CO(2) concentrations without reductions in
      photosynthetic capacity. However, given the lack of growth stimulation, the fate
      of the additionally assimilated carbon remains uncertain.

PMID- 20700743
TI  - Repression of both isoforms of disproportionating enzyme leads to higher malto
      oligosaccharide content and reduced growth in potato.
AB  - Two glucanotransferases, disproportionating enzyme 1 (StDPE1) and
      disproportionating enzyme 2 (StDPE2), were repressed using RNA interference
      technology in potato, leading to plants repressed in either isoform individually,
      or both simultaneously. This is the first detailed report of their combined
      repression. Plants lacking StDPE1 accumulated slightly more starch in their
      leaves than control plants and high levels of maltotriose, while those lacking
      StDPE2 contained maltose and large amounts of starch. Plants repressed in both
      isoforms accumulated similar amounts of starch to those lacking StDPE2. In
      addition, they contained a range of malto-oligosaccharides from maltose to
      maltoheptaose. Plants repressed in both isoforms had chlorotic leaves and did not
      grow as well as either the controls or lines where only one of the isoforms was
      repressed. Examination of photosynthetic parameters suggested that this was most
      likely due to a decrease in carbon assimilation. The subcellular localisation of
      StDPE2 was re-addressed in parallel with DPE2 from Arabidopsis thaliana by
      transient expression of yellow fluorescent protein fusions in tobacco. No
      translocation to the chloroplasts was observed for any of the fusion proteins,
      supporting a cytosolic role of the StDPE2 enzyme in leaf starch metabolism, as
      has been observed for Arabidopsis DPE2. It is concluded that StDPE1 and StDPE2
      have individual essential roles in starch metabolism in potato and consequently
      repression of these disables regulation of leaf malto-oligosaccharides, starch
      content and photosynthetic activity and thereby plant growth possibly by a
      negative feedback mechanism.

PMID- 20700746
TI  - The premamillary artery--a microanatomical study.
AB  - BACKGROUND: The microanatomical parameters of the premamillary artery (PMA) for
      the different configurations of the posterior communicating artery-adult
      (aPComA), hypoplastic (hPComA) and foetal (fPComA) were assessed and analysed. A
      comparative study with relevance to the neurosurgical practice has been carried
      out. METHOD: Red-coloured latex was injected in 35 human cadaver brains and a
      microanatomical dissection was performed. The area of emergence, the diameter,
      the length and the zone of penetration of the PMA were accessed. RESULTS: Seventy
      PComA were found and 96 PMA were identified. In more than 85% of the cases, the
      diameter of the PMA largely surpassed the diameter of the other perforating
      vessels. In the aPComA group, the PMA was a single branch in 72.4% of the cases
      with mean diameter of 0.52 mm and average length of 13.22 mm. PMA was found to
      originate from the middle third in 60.5%. For the hPComA group, in 66.7% of the
      cases, one PMA with mean diameter of 0.49 mm and average length 12.41 mm was
      found. In 60.9%, PMA originated from the middle third. For the fPComA group, in
      50.0% of the cases, one PMA was found with mean diameter of 0.39 mm, average
      length of 12.42 mm. PMA was found to originate from the anterior third in 41.7%
      of the cases. Emergence of the PMA from the internal carotid artery and from the
      P2 segment of the posterior cerebral artery was also documented. CONCLUSION: For
      the aPComA and the hPComA groups, the typical PMA may be described as the largest
      and most constant perforating branch emerging from the anterior 2/3 of the PComA
      and reaching the paramedian perforate substance. The PMA of the fPComA generally
      conforms to these characteristics but it is usually thinner, frequently
      duplicated and with higher percent of atypical emergence. These anatomical
      peculiarities may facilitate the intraoperative identification and preservation
      of the PMA when dealing with vascular or neoplastic pathologies with parasellar
      or interpeduncular extension.

PMID- 20700745
TI  - Achalasia: will genetic studies provide insights?
AB  - Despite increasing understanding of the pathophysiology of achalasia, the
      etiology of this esophageal motility disorder remains largely unknown. However,
      the occurrence of familial achalasia and its association with well-defined
      genetic syndromes suggest the involvement of genetic factors. Mutant mouse models
      display gastrointestinal disturbances that are similar to those observed in
      achalasia patients. The candidate gene approach has revealed some promising
      results; however, it has not established conclusive links to specific genes so
      far. The aim of this review was to summarize current knowledge of the genetics of
      achalasia. We also discuss the extent to which our understanding of achalasia is
      likely to be enhanced through future molecular genetic research.

PMID- 20700747
TI  - The effect of lung-protective permissive hypercapnia in intracerebral pressure in
      patients with subarachnoid haemorrhage and ARDS. A retrospective study.
AB  - OBJECTIVE: Lung protective ventilation has a beneficial effect in treating
      patients with acute respiratory distress syndrome (ARDS). An effect of this
      ventilation modality is hypercapnia, which leads to increased cerebral blood
      flow. Since increased cerebral blood flow can induce brain oedema the question
      arises whether lung protective ventilation can be applied in patients with
      subarachnoid haemorrhage. METHODS: We retrospectively analysed 12 patients with
      subarachnoid haemorrhage who were ventilated with lung protective ventilation
      since they suffered of ARDS. Tidal volume was 5-8 ml/kg body weight, and positive
      end expiratory pressure was 10-15 cm H2O. Intracerebral pressure was continuously
      measured by intracerebral probe. RESULTS: Despite of hypercapnia (pCO2 50-60
      mmHg) there was no increase of the intracerebral pressure. Lung protective
      ventilation could be safely performed in patients with subarachnoid haemorrhage.
      CONCLUSION: Patients with higher Hunt and Hess grades of subarachnoid haemorrhage
      who are predominantly intubated and ventilated and most of them suffer from ARDS
      can receive lung protective ventilation. In our small patient collective, the
      occurring hypercapnia did not influence (increase) the intracerebral pressure.

PMID- 20700748
TI  - Spontaneous acute spinal subdural hematoma: spontaneous recovery from severe
      paraparesis--case report and review.
AB  - Spontaneous idiopathic acute spinal subdural hematomas are highly exceptional.
      Neurological symptoms are usually severe, and rapid diagnosis with MRI is
      mandatory. Surgical evacuation has frequently been used therapeutically; however,
      spontaneous recovery in mild cases has also been reported. We present a case of
      spontaneous recovery from severe paraparesis after spontaneous acute SSDH, and
      review the English-speaking literature.

PMID- 20700749
TI  - Accreditation of neurosurgical training programmes in Europe: report of JRAAC.

PMID- 20700750
TI  - Slow vasogenic fluctuations of intracranial pressure and cerebral near infrared
      spectroscopy--an observational study.
AB  - BACKGROUND/PURPOSE: Increased slow-wave activity in intracranial pressure (ICP)
      signifies an exhausted cerebrospinal compensatory reserve across a range of
      conditions. In this study, we attempted to describe synchronisation between slow
      waves of ICP and of near-infrared spectroscopy (NIRS) variables during controlled
      elevation of ICP. METHOD: Nineteen patients presenting with symptomatic
      hydrocephalus underwent a Computerised Infusion Test. NIRS-derived indices, ICP
      and arterial blood pressure (ABP) were recorded simultaneously. FINDINGS: ICP
      increased from 9.3 (6.0) mmHg to a 17.1 (8.9) mmHg during infusion. Slow waves in
      ICP were accompanied by concurrent waves in each NIRS variable (including
      deoxygenated haemoglobin (Hb) and oxygenated haemoglobin (HbO2)) with a mean
      coherence of >0.7 and no significant phase shift. In the same bandwidth (0.3-1.8
      min(-1)), ABP fluctuations occurred with a coherence of 0.77 and phase lead of 40
      degrees  with respect to ICP. The power of ICP slow waves increased significantly
      during infusion plateau with a corresponding increase in power of Hb waves.
      CONCLUSIONS: Slow fluctuations in cerebral oximetry as detected by NIRS coincide
      with and are implicated in the origin of ICP slow waves and increases during
      periods of exhausted cerebrospinal compensatory reserve. NIRS may be used as a
      non-invasive marker of increased ICP slow waves (and therefore reduced CSF
      compensatory reserve).

PMID- 20700751
TI  - Training in endoscopic endonasal transsphenoidal surgery using a skull model and
      eggs.
AB  - BACKGROUND: Recently, endoscopic pituitary surgery is increasingly being used in
      pituitary surgery. Compared to conventional microscopic pituitary surgery,
      outcomes have been non-inferior, so endoscopic pituitary surgery has become an
      established surgical technique. However, this is a highly specialized surgery and
      sophisticated surgical techniques are required. We report our development of a
      training model for endoscopic endonasal transsphenoidal surgery. METHODS: Our
      training model is constructed using a skull model and eggs. The sella turcica of
      the skull model is hollowed out and an egg is placed. The bottom of the egg
      simulates the sella turcica floor and the egg contents simulate a tumor. Training
      is conducted using this model in an actual operating room with actual surgical
      instruments. RESULTS: This model is highly realistic and is within acceptable
      limits as a surgical simulation. Since practice can be repeated, this model is
      effective for familiarization with endoscopic imaging and to increase technical
      skills such as drilling and curetting. In addition, variations in eggs, ranging
      from raw eggs to boiled eggs, can be used to simulate various tumors for
      training. CONCLUSIONS: This training model using a skull model and eggs is useful
      to improve surgical techniques in endoscopic endonasal transsphenoidal surgery.

PMID- 20700752
TI  - A novel method for coral explant culture and micropropagation.
AB  - We describe here a method for the micropropagation of coral that creates progeny
      from tissue explants derived from a single polyp or colonial corals. Coral tissue
      explants of various sizes (0.5-2.5 mm in diameter) were manually microdissected
      from the solitary coral Fungia granulosa. Explants could be maintained in an
      undeveloped state or induced to develop into polyps by manipulating environmental
      parameters such as light and temperature regimes, as well as substrate type.
      Fully developed polyps were able to be maintained for a long-term in a closed sea
      water system. Further, we demonstrate that mature explants are also amenable to
      this technique with the micropropagation of second-generation explants and their
      development into mature polyps. We thereby experimentally have established coral
      clonal lines that maintain their ability to differentiate without the need for
      chemical induction or genetic manipulation. The versatility of this method is
      also demonstrated through its application to two other coral species, the
      colonial corals Oculina patigonica and Favia favus.

PMID- 20700753
TI  - Incidence of bacterial coinfection with respiratory syncytial virus
      bronchopulmonary infection in pediatric inpatients.
AB  - Bacterial coinfection occurs in pediatric bronchopulmonary infections caused by
      respiratory syncytial virus (RSV), but the incidence is uncertain. Our subjects
      are 188 pediatric inpatients having RSV bronchopulmonary infection in two
      hospitals in Chiba Prefecture between 2005 and 2007. On admission, antigen
      detection kits using nasopharyngeal aspirate were performed to detect RSV
      infection and washed sputum bacterial culture was performed to detect bacterial
      infection. Of the 188 pediatric inpatients with RSV bronchopulmonary infection,
      95 (50.5%) patients were aged less than 1 year, 57 (30.3%) were aged 1-2 years,
      and 36 (19.1%) were aged 2 years or more. Thirty-six (19.1%) patients were
      associated with bronchial asthma attacks. Pathogenic bacteria were predominantly
      isolated from 43.6% of the patients. The three most frequently isolated bacteria
      were Haemophilus influenzae (43.9%), Streptococcus pneumoniae (36.6%), and
      Moraxella catarrhalis (29.3%). We found that 38.9% of H. influenzae strains were
      beta-lactamase-nonproducing ampicillin-resistant strains. All S. pneumoniae
      strains were penicillin G (PcG) sensitive. However, 21.9% of S. pneumoniae
      strains showed PcG minimum inhibitory concentration values of 2 MUg/ml. RSV
      bronchopulmonary infections in hospitalized children are often associated with
      antimicrobial-resistant bacterial infection in their lower airways. These results
      indicate that we should be aware of bacterial coinfections in the management of
      pediatric inpatients with RSV bronchopulmonary infection.

PMID- 20700754
TI  - A pre- and postoperative bacteriological study of chronic suppurative otitis
      media.
AB  - BACKGROUND: Although many bacteriological studies on preoperative otorrhea in
      patients with chronic suppurative otitis media (CSOM) have been performed, there
      are few studies on postoperative otorrhea. In this study, we analyzed the
      pathogenic microorganisms, changes in the bacterial species before and after
      surgery, and the antibiotic sensitivity on preoperative and postoperative
      cultures. METHODS: This was a retrospective study of 87 postoperative otorrhea
      patients who were part of a sample of 1,754 patients with CSOM who underwent
      tympanomastoidectomy; preoperative and postoperative otorrhea samples were
      obtained from January 2002 to April 2009. We analyzed patients with postoperative
      otorrhea divided into two groups: those with early onset (<3 months after
      surgery, n = 45) and those with late onset (>3 months after surgery, n = 42)
      otorrhea. RESULTS: Four species of organisms, methicillin-sensitive
      Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA),
      Pseudomonas, and coagulase-negative Staphylococcus (CNS), showed higher
      prevalence than others on both the preoperative and postoperative cultures. When
      we compared the early and late onset otorrhea groups, we found that 'no growth'
      was significantly higher in the early onset group (n = 19 vs. n = 5), whereas
      MSSA was significantly higher in the late onset group (n = 1 vs. n = 12). Of the
      67 patients with positive preoperative cultures, 15 (22.4%) had the same bacteria
      after surgery, 34 (50.8%) had other bacteria, 2 (3.0%) had fungi, and 16 (23.8%)
      showed no growth on postoperative bacteriological testing. MSSA (9%) and MRSA
      (16.7%) were rarely recultured after surgery, whereas Pseudomonas was recultured
      frequently (61.5%). CONCLUSION: Unlike MSSA and MRSA, ciprofloxacin-resistant P.
      aeruginosa (CRP) occasionally causes early onset postoperative otorrhea due to
      the lack of highly potent antibiotics against this species. The success rate of
      infection control by surgery and antibiotics was low for CRP.

PMID- 20700756
TI  - Changes in mitochondrial dynamics during amyloid beta-induced PC12 cell
      apoptosis.
AB  - Changes in mitochondrial morphology and dynamics influence mitochondrial function
      and ultimately damage neurons in Alzheimer's disease (AD). Amyloid beta (Abeta)
      is a major factor in the pathogenesis of AD. Although it has been proved that
      Abeta can affect the dynamics of mitochondria, there is little known on the
      precise dynamic process. Thus, MTT, Hoechst 33342, and Annexin V/PI analysis were
      used to study Abeta(25-35) neurotoxity on PC12 cells, live cell station and image
      processing were applied to study the moving parameters and characters of
      mitochondria. We also studied changes of mitochondrial membrane potential and
      reactive oxygen species production. The results showed that long-term exposure of
      PC12 cells to Abeta(25-35) resulted in increase of mitochondrial number and
      decrease of mitochondrial length and size, which presented fluctuated during
      early time and dramatic changes occurred after 6 h. Low concentration exposure
      caused little mitochondrial changes before 24 h while short time exposure induced
      mitochondrial fragmentation that could be recovered to normal. Mitochondrial
      membrane potential dissipation and reactive oxygen species production were
      observed, as well as apparent cell apoptosis with significant morphological
      changes. These data suggest that mitochondrial fission can be reversed during
      Abeta(25-35)-induced PC12 cell apoptosis, depending on the concentration and
      exposure time of Abeta(25-35), which may be helpful in AD prevention and therapy.

PMID- 20700755
TI  - Effects of estrogen receptor antagonist on biological behavior and expression of
      growth factors in the prolactinoma MMQ cell line.
AB  - The relationship between estrogen and pituitary prolactinoma is well documented.
      The biological effects of estrogen are mainly mediated by estrogen receptor alpha
      (ERalpha). Several lines of evidence demonstrate that growth factors such as
      pituitary tumor transforming gene (PTTG), basic fibroblast growth factor (bFGF),
      transforming growth factor beta1 (TGFbeta1), transforming growth factor beta3
      (TGFbeta3), and transforming growth factor beta receptor type II (TGFbetaRII)
      play an important role in prolactinoma pathogenesis induced by estrogen, but the
      relationship between ERalpha and such growth factors is still unclear. The aims
      of this study are to investigate the functional role of ERalpha in proliferation,
      prolactin (PRL) secretion, and expression of the above-mentioned growth factors
      in MMQ cells in the absence of estrogen and to discuss the feasibility of using
      an estrogen receptor antagonist to treat prolactinoma. Fulvestrant, a "pure"
      antiestrogen without any estrogen-like activity, was used to block expression of
      ERalpha in the MMQ cell line. Proliferation and PRL secretion of MMQ cells were
      measured using CellTiter 96((r)) AQueous One Solution Cell Proliferation Assay
      (MTS) and the enzyme-linked immunosorbent assay (ELISA) method. Levels of
      ERalpha, PTTG, bFGF, TGFbeta1, TGFbeta3, and TGFbetaRII were analyzed by real
      time polymerase chain reaction (PCR) and Western blot. Fulvestrant significantly
      inhibited cell proliferation (up to 60.80%) and PRL secretion (up to 77.95%), and
      changed expression of TGFbeta3 and TGFbetaRII in the absence of estrogen. In
      conclusion, ERalpha plays an important functional role in proliferation and PRL
      secretion of pituitary prolactinomas and also can change expression of some
      growth factors even under the condition of no estrogen. Fulvestrant could
      potentially be an effective therapy for treating such tumors.

PMID- 20700757
TI  - Beliefs about and attitudes toward gambling in French-speaking Switzerland.
AB  - The present study aims to analyze attitudes and beliefs of the French-speaking
      general Swiss population (n = 2500; female n = 1280; mean age = 43 years) as
      regards gambling, which are to date almost exclusively studied in the North
      American and Australian contexts. Beliefs related to gambling include the
      perception of the effectiveness of preventive measures toward gambling, the
      comparative risk assessment of different addictive behaviors, the perceived risks
      of different types of gambling and attitudes are related to the gambler's
      personality. The general population perceived gambling rather negatively and was
      conscious of the potential risks of gambling; indeed, 59.0% of the sample
      identified gambling as an addictive practice. Slot machines were estimated to
      bear the highest risk. Compared with women and older people, men and young people
      indicated more positive beliefs about gambling; they perceived gambling as less
      addictive, supported structural preventive measures less often, and perceived
      gambling as a less serious problem for society. Gamblers were more likely to put
      their practices into perspective, perceiving gambling more positively than non
      gamblers. General population surveys on such beliefs can deliver insights into
      preventive actions that should be targeted to young men who showed more favorable
      views of gambling, which have been shown to be associated with increased risk for
      problematic gambling.

PMID- 20700759
TI  - Establishment of a multiplex RT-PCR assay to detect different lineages of swine
      H1 and H3 influenza A viruses.
AB  - Classical swine H1N1, emerging European avian-like H1N1 and human-like H3N2
      lineages are co-circulating in the swine population in China. The reverse
      transcriptase polymerase chain reaction (RT-PCR) assay is an effective method for
      use in influenza surveillance. In this study, a multiplex RT-PCR method was
      developed for simultaneous identification of hemagglutinin (HA) genes derived
      from the three lineages of swine influenza viruses. Three primer sets were
      designed and aimed specifically at HA genes of these viral lineages. The
      specificity of the assay showed that the established methods could efficiently
      differentiate the HA genes of classical swine H1N1, European avian-like H1N1, and
      human-like H3N2 viruses while other viruses such as classical swine fever virus,
      porcine reproductive and respiratory syndrome virus, pseudorabies virus, and
      porcine circovirus type 2, could not be detected. The assay showed a sensitivity
      of 1 x 10(2.5) 50% egg infectious dose for each virus lineage. The comparison of
      the results with those obtained from the analysis of 300 swine tracheal swab
      samples by means of virus isolation showed a high level of agreement. This
      multiplex RT-PCR method provides a rapid and specific swine influenza diagnostic
      tool that also has the potential for investigating the epidemiology of different
      lineages of swine influenza virus prevalent currently in China.

PMID- 20700758
TI  - Exogenous MD-2 confers lipopolysaccharide responsiveness to human corneal
      epithelial cells with intracellular expression of TLR4 and CD14.
AB  - In the present study, we aimed to investigate the responsiveness of human corneal
      epithelial cells (HCECs) to lipopolysaccharide (LPS) in vitro and to elucidate
      the underlying molecular mechanism(s) controlling the LPS responsiveness. The
      expression and subcellular localization of toll-like receptor 4 (TLR4) and CD14
      and the expression of myeloid differentiation (MD)-2 were studied in SDHCEC1
      cells, one HCEC cell line. Upon exposure to different concentrations of LPS, cell
      responses were evaluated by examining nuclear factor-kappaB (NF-kappaB)
      activation and the production of interleukin (IL)-8. The influence of soluble MD
      2 on LPS responsiveness were assessed in SDHCEC1 cells pretreated with MD-2
      containing conditioned medium before LPS challenge. SDHCEC1 cells expressed both
      TLR4 and CD14 intracellularly and had no detectable expression of MD-2
      transcripts. Unresponsiveness to LPS at doses of up to 1,000 ng/ml was observed
      in SDHCEC1 cells, which was evidenced by no evident NF-kappaB activation and IL-8
      production. The addition of MD-2 conditioned medium significantly induced NF
      kappaB activation and enhanced the production of IL-8 as compared with the
      treatment with the control medium (p < 0.05). Meanwhile, the total mRNA amounts
      of TLR4 and CD14 and the surface expression of the two proteins were
      significantly (p < 0.05) increased by the pretreatment with MD-2 conditioned
      medium. LPS hyporesponsiveness of HCECs is largely due to deficient LPS receptor
      complex formation caused by lack of MD-2 expression. Exogenous MD-2 is capable of
      restoring the LPS responsiveness, at least partially, through promoting the
      surface expression of TLR4 and CD14.

PMID- 20700760
TI  - Monozygotic twins with discordant karyotypes following preimplantation genetic
      screening and single embryo transfer: case report.
AB  - PURPOSE: to report a case of monozygotic monochorial diamniotic twins with
      discordant karyotypes. METHODS AND RESULTS: the pregnancy was achieved following
      a treatment cycle with intracytoplasmic sperm injection (ICSI) and
      preimplantation genetic screening (PGS) for chromosomes X, Y, 13, 16, 18, 21, 22.
      One embryo euploid for studied chromosomes was transferred. Prenatal
      ultrasonography revealed monozygotic twins. One fetus had growth retardation,
      multiple organ abnormalities and polyhydramnion. The other twin had normal
      ultrasound appearance. Delivery on week 29 of gestation resulted in the birth of
      two females, a stillborn twin with karyotype 45,XX,-13[12]/46,XX,r(13)[3] and a
      healthy twin with normal karyotype. CONCLUSIONS: the discordance in the twins'
      karyotypes originated from a mosaic embryo. Structural chromosomal abnormality of
      the affected twin could not be revealed using standard PGS investigation. Embryo
      splitting occurred probably due to apoptotic process in an early stage of embryo
      development. Apoptosis represents one of the possible mechanisms which can
      explain the embryo twinning process globally.

PMID- 20700761
TI  - Evaluation of micronucleus and erythrocytic nuclear abnormalities in Balkan whip
      snake Hierophis gemonensis.
AB  - Over recent years, changes of erythrocytic nuclei have been increasingly used to
      evaluate genotoxic effects of different compounds such as polycyclic aromatic
      hydrocarbons (benzo-a-pyrene, naphthalene, beta-naphthoflavone), heavy metals
      (cadmium, mercury), textile mill effluent especially in aquatic ecosystem.
      However, in fish, both micronuclei and erythrocytic nuclear abnormalities also
      appear spontaneously and their frequency can be seasonally dependent. The aim of
      the study was to evaluate the frequency of micronuclei (MN), nuclear
      abnormalities (NA) including vacuolated nuclei (VN) and cytoplasmic vacuoles (CV)
      in erythrocytes of Balkan whip snake Hierophis gemonensis and establish the level
      of spontaneous appearance during the annual cycle. Average frequency of NA was
      10.89 +/- 4.72% while the MN (0.03 +/- 0.03%) and VN (0.04 +/- 0.08%) were seldom
      detected. NA significantly positively correlated with MN (r = 0.319; P < 0.05)
      and VN (r = 0.363; P < 0.05). Appearance of CV did not correlate with other
      measured parameters and average frequency was 11.06 +/- 8.33%. Significant
      seasonal variation was found in NA appearance with the lowest value in spring and
      the highest in winter. VN increase was observed in autumn. MN and CV levels
      varied between seasons but not significantly. Considering the biological cycle,
      frequency of NA, VN, MN and CV recorded in pre-hibernation/hibernation increased
      compared to the active phase, but only NA elevation was significant. Although the
      obtained results showed differences according to sex, statistical analysis of
      measured parameters showed the same pattern of seasonal variation in both sexes.

PMID- 20700762
TI  - Quantification of toxins in a Cry1Ac + CpTI cotton cultivar and its potential
      effects on the honey bee Apis mellifera L.
AB  - Transgenic Cry1Ac + CpTI cotton (CCRI41) is increasingly planted throughout
      China. However, negative effects of this cultivar on the honey bee Apis mellifera
      L., the most important pollinator for cultivated ecosystem, remained poorly
      investigated. The objective of our study was to evaluate the potential side
      effects of transgenic Cry1Ac + CpTI pollen from cotton on young adult honey bees
      A. mellifera L. Two points emphasized the significance of our study: (1) A higher
      expression level of insecticidal protein Cry1Ac in pollen tissues was detected
      (when compared with previous reports). In particular, Cry1Ac protein was detected
      at 300 +/- 4.52 ng g(-1) [part per billion (ppb)] in pollen collected in July,
      (2) Effects on chronic mortality and feeding behaviour in honey bees were
      evaluated using a no-choice dietary feeding protocol with treated pollen, which
      guarantee the highest exposure level to bees potentially occurring in natural
      conditions (worst case scenario). Tests were also conducted using imidacloprid
      treated pollen at a concentration of 48 ppb as positive control for sublethal
      effect on feeding behaviour. Our results suggested that Cry1Ac + CpTI pollen
      carried no lethal risk for honey bees. However, during a 7-day oral exposure to
      the various treatments (transgenic, imidacloprid-treated and control), honey bee
      feeding behaviour was disturbed and bees consumed significantly less CCRI41
      cotton pollen than in the control group in which bees were exposed to
      conventional cotton pollen. It may indicate an antifeedant effect of CCRI41
      pollen on honey bees and thus bees may be at risk because of large areas are
      planted with transgenic Bt cotton in China. This is the first report suggesting a
      potential sublethal effect of CCRI41 cotton pollen on honey bees. The
      implications of the results are discussed in terms of risk assessment for bees as
      well as for directions of future work involving risk assessment of CCRI41 cotton.

PMID- 20700763
TI  - Exposure to 17alpha-ethynylestradiol causes dose and temporally dependent changes
      in intersex, females and vitellogenin production in the Sydney rock oyster.
AB  - Although mounting evidence suggests exposure to estrogenic contaminants increases
      vitellogenin production in molluscs, demonstration of dose-response relationships
      and knowledge of the temporal nature of the vitellogenin response with continual
      exposure is currently lacking for biomarker utility. To address this knowledge
      gap, adult Sydney rock oysters, Saccostrea glomerata, were exposed to a range of
      environmentally relevant concentrations of 17alpha-ethynylestradiol (EE2) (0,
      6.25, 12.5, 25 or 50 ng/l) in seawater under laboratory conditions. Vitellogenin
      induction and gonadal development was assessed following 4, 21 and 49 days
      exposure to EE2. Vitellogenin was found to increase in a dose dependent manner
      with EE2 exposure for females (4 and 49 days) and males (4 and 21 days).
      Histological examination of gonads revealed a number of individuals exhibited
      intersex (ovotestis) in 50 ng/l EE2 (after 21 days) and in 6.25 and 12.5 ng/l EE2
      (after 49 days). Furthermore, a significant shift towards females was observed
      following 49 days exposure at 50 ng/l EE2 suggesting estrogenic exposure is
      capable of facilitating a progression for protandric males from male-intersex
      female gametal status. Increases in female vitellogenin (4 days) were predictive
      of later increases in female developmental stages at 21 days and increases in
      oocyte area following 49 days. Male vitellogenin (4 days) was predictive of
      decreased male percentages and lower male developmental stages at 49 days.
      Vitellogenin in S. glomerata is a predictive biomarker of estrogenic exposure and
      effect if sampled soon after exposure and at the commencement of a gonadal
      development cycle.

PMID- 20700764
TI  - Phytobenthos and phytoplankton community changes upon exposure to a sunflower oil
      spill in a South African protected freshwater wetland.
AB  - The occurrence of a sunflower oil spill in 2007 in the Con Joubert Bird Sanctuary
      freshwater wetland, South Africa, inhibited the growth of sensitive phytoplankton
      species and promoted that of tolerant species. The algal divisions Chlorophyta
      and Euglenophyta were well represented in the sunflower oil contaminated water,
      especially the species Euglena sociabilis, Phacus pleuronectes and Chlamydomonas
      africana. Young and mature resting zygotes of Chlamydomonas africana were
      recorded in high abundance at all the sunflower oil contaminated sampling sites.
      The phytobenthos diversity and abundance were significantly suppressed and
      negatively associated with low Dissolved Oxygen concentrations and the negative
      redox potential of the bottom sediment. At the intracellular level, phytoplankton
      chlorophyll a and b concentrations as physiological variables were more sensitive
      indicators of the adverse effects of sunflower oil than the 72 h Selenastrum
      capricornutum algal bioassay conducted.

PMID- 20700765
TI  - The dnaK gene as a molecular marker for the classification and discrimination of
      the Lactobacillus casei group.
AB  - It is hard to accurately identify specific species of the Lactobacillus casei
      group using phenotypic techniques alone. Some strains of this species group are
      considered to be probiotic and are widely applied in the food industry. In this
      study, we compared the use of two phylogenetic markers, the 16S rRNA and dnaK
      genes, for species discrimination of the members of the L. casei group using
      sequencing and RFLP. The results showed that L. casei, Lactobacillus paracasei,
      Lactobacillus zeae and Lactobacillus rhamnosus could be clearly distinguished
      based on the dnaK gene. The average sequence similarity for the dnaK gene (87.8%)
      among type strains was significantly less than that of the 16S rRNA sequence
      (99.1%). Therefore, the dnaK gene can be proposed as an additional molecular
      phylogenetic marker for L. casei that provides higher resolution than 16S rRNA.
      Species-specific RFLP profiles of the Lactobacillus strains were obtained with
      the enzyme ApoI. Our data indicate that the phylogenetic relationships between
      these strains are easily resolved using sequencing of the dnaK gene or RFLP
      assays.

PMID- 20700766
TI  - 68Ga-DOTA-TATE PET vs. 123I-MIBG in identifying malignant neural crest tumours.
AB  - PURPOSE: We aimed to compare imaging with (123)I-MIBG and (68)Ga-DOTA-TATE in
      neural crest tumours (NCT) to see if the latter could offer more advantage in
      detecting extra lesions and have higher sensitivity for malignant lesions.
      PROCEDURES: We retrospectively reviewed 12 patients (M = 10, F = 2; age range 20
      71 years) with NCT (phaeochromocytomas = 7, paragangliomas = 4, medullary thyroid
      cancer = 1) who underwent both (68)Ga-DOTA-TATE positron emission tomography
      (PET) or PET/computed tomography (CT) and (123)I-MIBG single-photon emission
      computed tomography within 6 months. Visual assessment of all lesions and
      measurement of target/non-target (T/N) ratio in selected lesions were performed.
      Five patients (aged 50 or less) had SDHB screening results correlated with
      imaging results of both radiopharmaceuticals. All patients had contrast-enhanced
      CT and/or other cross-sectional imaging. RESULTS: (68)Ga-DOTA-TATE PET showed
      tumour lesions in ten out of 12 patients with confirmed disease, while (123)I
      MIBG showed lesions in five out of 12 patients. In one patient, both (68)Ga-DOTA
      TATE PET and (123)I-MIBG were negative, but CT, magnetic resonance imaging, and 2
      deoxy-2-[(18)F]fluoro-D-glucose PET scans identified a lesion in the thorax.
      (68)Ga-DOTA-TATE and (123)I-MIBG detected a total of 30 lesions, of which 29/30
      were positive with (68)Ga-DOTA-TATE and 7/30 with (123)I-MIBG. We also found
      higher incidence of SDHB positive results in patients with positive (68)Ga-DOTA
      TATE. CONCLUSION: Our limited data suggest that (68)Ga-DOTA-TATE is a better
      imaging agent for NCT and detects significantly more lesions with higher T/N
      ratio compared to (123)I-MIBG. (68)Ga-DOTA-TATE was more likely to detect
      malignant lesions as indicated by correlating imaging results with SDHB
      screening.

PMID- 20700767
TI  - Characterization of the inflammatory response in a photothrombotic stroke model
      by MRI: implications for stem cell transplantation.
AB  - PURPOSE: The aim of this study was to evaluate the specificity of magnetic
      resonance imaging (MRI) contrast in a photothrombotic (PT) stroke model with and
      without engraftment of superparamagnetic iron oxide (SPIO)-labeled stem cells.
      PROCEDURES: We monitored animals with PT stroke versus animals with PT stroke and
      stem cell engraftment by T(2)/T(2)*w MRI 4-8 h and 2, 4, 6/7 and 14 days after PT
      induction. Results were correlated with immunohistochemistry. RESULTS: T(2)*w MRI
      images showed hypointense contrast due to the accumulation of inflammatory cells
      and corresponding iron accumulation and glial scar formation in the border zone
      of the lesion, similar as what was observed for SPIO-labeled cells. Histological
      analysis was thus indispensable to distinguish between labeled transplanted cells
      and immune cells. CONCLUSION: These results raise caution regarding the non
      invasive monitoring of SPIO-labeled transplanted stem cells by MRI in models that
      result in a strong inflammatory response.

PMID- 20700768
TI  - Day-to-day test-retest variability of CBF, CMRO2, and OEF measurements using
      dynamic 15O PET studies.
AB  - PURPOSE: We assessed test-retest variability of cerebral blood flow (CBF),
      cerebral blood volume (CBV), cerebral metabolic rate of oxygen (CMRO(2)), and
      oxygen extraction fraction (OEF) measurements derived from dynamic (15)O positron
      emission tomography (PET) scans. PROCEDURES: In seven healthy volunteers,
      complete test-retest (15)O PET studies were obtained; test-retest variability and
      left-to-right ratios of CBF, CBV, OEF, and CMRO(2) in arterial flow territories
      were calculated. RESULTS: Whole-brain test-retest coefficients of variation for
      CBF, CBV, CMRO(2), and OEF were 8.8%, 13.8%, 5.3%, and 9.3%, respectively. Test
      retest variability of CBV left-to-right ratios was <7.4% across all territories.
      Corresponding values for CBF, CMRO(2), and OEF were better, i.e., <4.5%, <4.0%,
      and <1.4%, respectively. CONCLUSIONS: The test-retest variability of CMRO(2)
      measurements derived from dynamic (15)O PET scans is comparable to within-session
      test-retest variability derived from steady-state (15)O PET scans. Excellent
      regional test-retest variability was observed for CBF, CMRO(2), and OEF.
      Variability of absolute CBF and OEF measurements is probably affected by
      physiological day-to-day variability of CBF.

PMID- 20700769
TI  - Barriers to formal emergency obstetric care services' utilization.
AB  - Access to appropriate health care including skilled birth attendance at delivery
      and timely referrals to emergency obstetric care services can greatly reduce
      maternal deaths and disabilities, yet women in sub-Saharan Africa continue to
      face limited access to skilled delivery services. This study relies on
      qualitative data collected from residents of two slums in Nairobi, Kenya in 2006
      to investigate views surrounding barriers to the uptake of formal obstetric
      services. Data indicate that slum dwellers prefer formal to informal obstetric
      services. However, their efforts to utilize formal emergency obstetric care
      services are constrained by various factors including ineffective health decision
      making at the family level, inadequate transport facilities to formal care
      facilities and insecurity at night, high cost of health services, and
      inhospitable formal service providers and poorly equipped health facilities in
      the slums. As a result, a majority of slum dwellers opt for delivery services
      offered by traditional birth attendants (TBAs) who lack essential skills and
      equipment, thereby increasing the risk of death and disability. Based on these
      findings, we maintain that urban poor women face barriers to access of formal
      obstetric services at family, community, and health facility levels, and efforts
      to reduce maternal morbidity and mortality among the urban poor must tackle the
      barriers, which operate at these different levels to hinder women's access to
      formal obstetric care services. We recommend continuous community education on
      symptoms of complications related to pregnancy and timely referral. A focus on
      training of health personnel on "public relations" could also restore confidence
      in the health-care system with this populace. Further, we recommend improving the
      health facilities in the slums, improving the services provided by TBAs through
      capacity building as well as involving TBAs in referral processes to make access
      to services timely. Measures can also be put in place to enhance security in the
      slums at night.

PMID- 20700770
TI  - Regulation of hepatocyte lipid metabolism and inflammatory response by 25
      hydroxycholesterol and 25-hydroxycholesterol-3-sulfate.
AB  - Dysregulation of lipid metabolism is frequently associated with inflammatory
      conditions. The mechanism of this association is still not clearly defined.
      Recently, we identified a nuclear oxysterol, 25-hydroxycholesterol-3-sulfate
      (25HC3S), as an important regulatory molecule involved in lipid metabolism in
      hepatocytes. The present study shows that 25HC3S and its precursor, 25
      hydroxycholesterol (25HC), diametrically regulate lipid metabolism and
      inflammatory response via LXR/SREBP-1 and IkappaBalpha/NFkappaB signaling in
      hepatocytes. Addition of 25HC3S to primary rat hepatocytes decreased nuclear LXR
      and SREBP-1 protein levels, down-regulated their target genes, acetyl CoA
      carboxylase 1 (ACC1), fatty acid synthase (FAS), and SREBP-2 target gene HMG
      reductase, key enzymes involved in fatty acid and cholesterol biosynthesis.
      25HC3S reduced TNFalpha-induced inflammatory response by increasing cytoplasmic
      IkappaBalpha levels, decreasing NFkappaB nuclear translocation, and consequently
      repressing expression of NFkappaB-dependent genes, IL-1beta, TNFalpha, and TRAF1.
      NFkappaB-dependent promoter reporter gene assay showed that 25HC3S suppressed
      luciferase activity in the hepatocytes. In contrast, 25HC elicited opposite
      effects by increasing nuclear LXR and SREBP-1 protein levels, and by increasing
      ACC1 and FAS mRNA levels. 25HC also decreased cytoplasmic IkappaBalpha levels and
      further increased TNFalpha-induced NFkappaB activation. The current findings
      suggest that 25HC and 25HC3S serve as potent regulators in cross-talk of lipid
      metabolism and inflammatory response in the hepatocytes.

PMID- 20700771
TI  - Basal cell carcinoma of the nipple in male patients with gastric cancer
      recurrence: report of a case.
AB  - Although basal cell carcinoma (BCC) is the most common dermatological malignancy
      arising from sun exposed skin, BCC of the nipple is extremely rare. To our
      knowledge only 34 cases have been reported. We report a 78-year-old man who was
      undergoing chemotherapy for liver metastasis of gastric cancer 1 year after
      surgery. The chief complaint was exudation and oozing from the nipple. A mass
      lesion was palpable and detected on mammography and enhanced computed tomography,
      and atypical cells were detected on cytological examination. Simple resection was
      performed because histopathological diagnosis of an intraoperative frozen section
      revealed BCC. Final pathological diagnosis was also BCC. The authors report this
      case and review the previous reports, and discuss the clinicopathologic
      characteristics and adequate treatment for this disease.

PMID- 20700772
TI  - Gene transfer to the cerebellum.
AB  - There are several diseases for which gene transfer therapy to the cerebellum
      might be practicable. In these studies, we used recombinant Tag-deleted SV40
      derived vectors (rSV40s) to study gene delivery targeting the cerebellum. These
      vectors transduce neurons and microglia very effectively in vitro and in vivo,
      and so we tested them to evaluate gene transfer to the cerebellum in vivo. Using
      a rSV40 vector carrying human immunodeficiency virus (HIV)-Nef with a C-terminal
      FLAG epitope, we characterized the distribution, duration, and cell types
      transduced. Rats received test and control vectors by stereotaxic injection into
      the cerebellum. Transgene expression was assessed 1, 2, and 4 weeks later by
      immunostaining of serial brain sections. FLAG epitope-expressing cells were seen,
      at all times after vector administration, principally detected in the Purkinje
      cells of the cerebellum, identified as immunopositive for calbindin. Occasional
      microglial cells were tranduced; transgene expression was not detected in
      astrocytes or oligodendrocytes. No inflammatory or other reaction was detected at
      any time. Thus, SV40-derived vectors can deliver effective, safe, and durable
      transgene expression to the cerebellum.

PMID- 20700773
TI  - [Biomedical techniques, chances and risks].

PMID- 20700774
TI  - [Biomedical engineering today : An overview from the viewpoint of the German
      Biomedical Engineering Society].
AB  - Biomedical engineering is characterized by the interdisciplinary co-operation of
      technology, science, and ways of thinking, probably more than any other
      technological area. The close interaction of engineering and information sciences
      with medicine and biology results in innovative products and methods, but also
      requires high standards for the interdisciplinary transfer of ideas into products
      for patients' benefits. This article describes the situation of biomedical
      engineering in Germany. It displays characteristics of the medical device
      industry and ranks it with respect to the international market. The research
      landscape is described as well as up-to-date research topics and trends. The
      national funding situation of research in biomedical engineering is reviewed and
      existing innovation barriers are discussed.

PMID- 20700775
TI  - [Principles of MR-guided interventions, surgery, navigation, and robotics].
AB  - The application of magnetic resonance imaging (MRI) as an imaging technique in
      interventional and surgical techniques provides a new dimension of soft tissue
      oriented precise procedures without exposure to ionizing radiation and
      nephrotoxic allergenic, iodine-containing contrast agents. The technical
      capabilities of MRI in combination with interventional devices and systems,
      navigation, and robotics are discussed.

PMID- 20700776
TI  - [Personalized medicine and individual healthcare : Medical and information
      technology aspects].
AB  - The individualization of medicine and healthcare appears to be following a
      general societal trend. The terms "personalized medicine" and "personal health"
      are used to describe this process. Here it must be emphasized that personalized
      medicine is not limited to pharmacogenomics, but that the spectrum of
      personalized medicine is much broader. Applications range from individualized
      diagnostics, patient-specific pharmacological therapy, therapy with individual
      prostheses and implants to therapy approaches using autologous cells, and from
      patient model-based therapy in the operating room, electronic patient records
      through to the individual care of patients in their home environment with the use
      of technical systems and services. Although in some areas practical solutions
      have already been found, most applications will not be fully developed for many
      years to come. Medical and information technology are essential to personalized
      medicine and personal health, each driving the other forward.

PMID- 20700777
TI  - [Neural prostheses and neuromodulation : Research and clinical practice in
      therapy and rehabilitation].
AB  - Stimulation of the nervous system with the aid of electrical active implants has
      changed the therapy of neurological diseases and rehabilitation of lost functions
      and has expanded clinical practice within the last few years. Alleviation of
      effects of neurodegenerative diseases, therapy of psychiatric diseases, the
      functional restoration of hearing as well as other applications have been
      transferred successfully into clinical practice. Other approaches are still under
      development in preclinical and clinical trials. The restoration of sight by
      implantable electronic systems that interface with the retina in the eye is an
      example how technological progress promotes novel medical devices. The idea of
      using the electrical signal of the brain to control technical devices and
      (neural) prostheses is driving current research in the field of brain-computer
      interfaces. The benefit for the patient always has to be balanced with the risks
      and side effects of those implants in comparison to medicinal and surgical
      treatments. How these and other developments become established in practice
      depends finally on their acceptance by the patients and the reimbursement of
      their costs.

PMID- 20700778
TI  - [Biomedical engineering supports surgical planning and interventions].
AB  - Fundamental changes were achieved with the introduction of minimally invasive
      surgery. In this context, innovations in microtechnology played a significant
      role in the deployment of new tools. Developments for further integration are
      still ongoing. Furthermore, decisive progress was made by the timely provision of
      individual patient data prior to surgery. These comprise imaging data,
      electrophysiological or functional recordings, and synthetic data gained by
      modeling and simulation of anatomical or physiological conditions. Aside from the
      technical aspects of supporting surgery, effective quality management and
      optimized workflow are essential for therapeutic success. The vision of
      autonomously operating robots has been dropped in favor of permanently conducted
      and supervised interventions with the support of intelligent tools for the
      surgeon. Recent advances in reconstruction and transplantation surgery by tissue
      engineering and molecular biology are only the beginning of new promising
      concepts.

PMID- 20700779
TI  - [Neuroimaging in medicine].
AB  - Neuroimaging has in recent years greatly contributed to our understanding of a
      wide range of aspects of central neurological diseases. These include the
      classification and localization of disease (e.g., in headache), the understanding
      of pathology (e.g., in Parkinson's disease), mechanisms of reorganization (e.g.,
      in stroke), and the subclinical progress of disease (e.g., in degenerative
      diseases). Apart form presurgical mapping, clinical applications of fMRI are
      limited. However, functional imaging enables the formulation of neurobiological
      hypotheses that can be tested clinically and is suited to test classical clinical
      hypotheses about how the brain works. Understanding the mechanisms and the site
      of pathology, e.g., in cluster headaches, will lead and has led to new
      therapeutic strategies. New methodological developments for neuroscientific
      applications are aimed at the integration of functional and morphological
      connectivity through a combination of magnetic resonance techniques (fMRI, DTI)
      and electrophysiological (EEG, MEG) recordings. In addition to stimulus-dependent
      activations, resting state activity has found increasing interest, for example,
      in sleep research and various psychiatric diseases (e.g., schizophrenia,
      borderline).

PMID- 20700780
TI  - [Molecular imaging in cancer therapy].
AB  - Targeted drugs that modulate the function of specific molecules in diseased
      tissues hold great promise for the treatment of many diseases, including
      malignant tumors. However, there are several challenges for the efficient
      evaluation of these drugs in clinical trials as well as for the use in clinical
      practice. These include (i) the selection of patients likely to benefit from
      treatment with a specific targeted drug, (ii) finding the right dose and dose
      schedule, (iii) monitoring target inhibition, and (iv) assessing tumor response
      to therapy. Standard anatomic imaging continues to play an important role for
      addressing these challenges, but molecular imaging provides several new
      opportunities to make the use of targeted drugs more efficient. Using molecular
      imaging, the expression of drug targets can be assessed noninvasively, the
      concentration of drugs can be measured in the tumor tissue, target inhibition can
      be monitored, and tumor response to therapy can be evaluated earlier than with
      anatomic imaging techniques. Therefore, it is expected that molecular imaging
      will play an increasing role for guiding molecularly defined therapeutic
      interventions.

PMID- 20700781
TI  - [Modern technology in cardiovascular medicine].
AB  - Despite basic physiologic principles being well known for more than 300 years,
      the diagnosis and therapy of cardiovascular diseases are still in their early
      beginnings. For example, 100 years ago sudden cardiac arrest was regarded as the
      result of toxic gases. The diagnosis of ventricular fibrillation or treatment
      with a defibrillator are very recent developments. We are currently experiencing
      a technological revolution, which is rapidly changing cardiovascular medicine.
      This publication is focused on electrical devices and tries to identify some of
      the innovation mainstreams using a few examples to demonstrate these. Four
      megatrends are explained in more detail: the influence of wireless technology,
      information technology, micro systems technology, and thinking in systems. This
      paper is aimed at stimulating active researchers and engineers to detect the
      rapid changes that we often do not observe in our daily work. The author hopes
      that this stimulation will lead to new ideas and combinations.

PMID- 20700782
TI  - [Assessment of benefit and efficiency of innovative medical devices].
AB  - Medical devices cover a wide spectrum of products with very different diagnostic
      and therapeutic applications. However, for market licensing, uniform rules apply.
      Uniform rules are also valid for coverage decisions in German health care. In
      this article, the criteria for the assessment of benefit and efficiency of
      innovative biomedical technologies are described from the perspective of the
      statutory health insurance system. The key concepts relevant in the mandatory
      health insurance' "innovation"' "benefit", and "economic efficiency" are
      characterized. Only measurable effects of an intervention which lead to a more
      than marginal improvement in prognosis, symptoms, or quality of life as compared
      to a standard treatment are considered as beneficial. An innovative device is,
      therefore, subject to a benefit assessment if it is not yet reimbursed (or not
      yet part of the benefit package), when it is relevant to the health care system
      and a high public interest exists. In addition, it is important to consider a
      positive benefit assessment as a part of the value added chain to avoid conflicts
      of interest. Within the scope of early technology assessment, some conclusions
      can already be drawn in the early developmental stage of a device.

PMID- 20700783
TI  - [Efficiency, risks, and advantages of using robotic support systems in
      interventional medicine].
AB  - During the past decade, robotic systems were evaluated for the first time in
      practically all surgical disciplines. With only a few exceptions (radical
      prostatectomy), mechatronic systems did not achieve a breakthrough in any field
      of application. Second generation robotic devices with better integration of
      complementary technologies (preoperative therapy planning, intraoperative
      diagnostic work-up, navigation, etc.) and augmented functionality are now ready
      to be introduced into clinical practice. It is hoped that the specific advantages
      of robotics will result in increased use compared to previous systems. Robotics
      is a key technology if new surgical strategies ("scarless surgery") are to
      succeed.

PMID- 20700784
TI  - [Nanomedicine : Magnetic nanoparticles for drug delivery and hyperthermia - new
      chances for cancer therapy].
AB  - The application of nanotechnology for the treatment, diagnosis, and monitoring of
      illnesses is summarized under the term nanomedicine. A particularly promising
      application is attributed to nanoparticular drug delivery systems. The goal of
      these new carrier systems is the selective enrichment of active substances in
      diseased tissue structures, an increase in bioavailability, the decrease of the
      active substance degradation and, above all, the reduction and/or avoidance of
      unwanted side effects. Apart from numerous nanosystems acting as carriers, the
      use of iron oxide nanoparticles has to be particularly emphasized. On the one
      hand, those particles are the carriers of the active substance and, on the other
      hand, can also be visualized with conventional imaging techniques (x-ray
      tomography, magnetic resonance imaging), called theranostic. In addition, they
      can be used for hyperthermia, another important supporting pillar of
      nanomedicine. Both procedures should lead to a personalized and goal-oriented
      therapy, which is of special medical and socioeconomic importance in view of the
      increasing number of cancer patients worldwide.

PMID- 20700785
TI  - [Medical technology and medical education].
AB  - The education of medical professionals is divided into medical studies,
      postgraduate training leading to the qualification as a specialist, and
      continuing professional development. During education, all scientific knowledge
      and practical skills are to be acquired, which enable the physician to practice
      responsibly in a specialized medical area. In the present article, relevant
      curricula are analyzed regarding the consideration of medical device-related
      topics, as the clinical application of medical technology has reached a central
      position in modern patient care. Due to the enormous scientific and technical
      progress, this area has become as important as pharmacotherapy. Our evaluation
      shows that medical device-related topics are currently underrepresented in the
      course of medical education and training and should be given greater
      consideration in all areas of medical education. Possible solutions are
      presented.

PMID- 20700786
TI  - [Pharmacological neuroenhancement and brain doping : Chances and risks].
AB  - Pharmacological neuroenhancement refers to the use of psychoactive substances by
      healthy subjects with the purpose of cognitive enhancement, e.g., vigilance,
      concentration, memory, or mood. "Brain doping", however, refers to the illicit
      use of a subcategory of these substances such as prescription drugs. This
      subcategory includes psychostimulants (e.g., amphetamines, methylphenidate),
      modafinil, antidementia drugs (acetylcholine-esterase inhibitors, memantine), and
      antidepressants (selective serotonin reuptake inhibitors) which are being
      prescribed for the treatment of ADHD (attention deficit/hyperactivity disorder),
      Alzheimer's disease, and depression. Only psychostimulants and modafinil show
      significant effects on concentration, attentiveness, and vigilance in healthy
      subjects. However, a general use by healthy persons can not be justified because
      of relevant side effects and safety risks. Caffeine for pharmacological
      neuroenhancement can be seen as an equally effective alternative. "Brain doping"
      raises numerous ethical and social concerns that require a continued discussion.
      Demands of liberalization should be critically questioned.

PMID- 20700787
TI  - [Use of a uniform questionnaire for blood and plasma donors].

PMID- 20700788
TI  - [Classification of toxic water pollutants].

PMID- 20700790
TI  - Association between clinical diagnostic tests and health-related quality of life
      surveys in patients with dry eye syndrome.
AB  - PURPOSE: This study was performed to assess the impact of dry eye on patients'
      quality of life (QOL) and to analyze the association between subjective symptoms
      and ocular surface findings of dry eye. METHODS: The study population consisted
      of 158 patients with dry eye aged 20 years or older who visited any of the 15
      medical care facilities enrolled in the study. The backgrounds and ocular
      findings of the patients were investigated, and their QOL was evaluated with the
      Japanese version of the 25-item National Eye Institute Visual Functioning
      Questionnaire (VFQ-25) and of the Medical Outcomes Study (MOS) 8-item Short-Form
      Health Survey (SF-8) to examine the association between subjective symptoms and
      ocular surface findings. RESULTS: Of the patients enrolled, 15 were men and 143
      were women, and their average age was 62.5 +/- 12.6 years. Sixty patients (38.0%)
      had comorbid Sjogren syndrome (SS). The results of Schirmer testing, fluorescein
      staining, and rose bengal staining for SS patients were significantly worse than
      those for the non-SS patients, but the VFQ-25 and SF-8 scores were not
      significantly different between the SS and non-SS patients. In the ocular surface
      findings, a weak association between the fluorescein staining scores and general
      vision scores, a subscale of the VFQ-25, was found. However, the ocular surface
      findings and VFQ-25/SF-8 results in the simple correlation analysis as well as in
      the multiple linear regression analysis showed no significant associations.
      CONCLUSIONS: Ocular surface findings and QOL scores of patients with dry eye
      appear to disagree. Therefore, it is necessary to address subjective symptoms and
      QOL scores in addition to examination findings when evaluating dry eye.

PMID- 20700791
TI  - Etiology of ocular diseases in elderly Amis aborigines in Eastern Taiwan (The
      Amis Eye Study).
AB  - PURPOSE: To determine the incidence of and risk factors associated with major
      ocular diseases in the elderly Amis population of Taiwan. METHODS: This
      population-based cross-sectional study is the most current survey of ocular
      diseases among elderly Amis. The overall response rate was 61.2%, with 2316
      participants screened. All ocular examinations were performed using a mobile
      ophthalmology setup staffed by an ophthalmologist with 30 years of experience.
      RESULTS: The mean age of the participants was 71.65 years. Cataracts were the
      most common ocular disease (82.6%), followed by pterygium (44.1%),
      arteriosclerotic changes in retinal vessels (35.7%), hypertensive retinopathy
      (18.5 %), age-related macular degeneration (5.2%), optic neuropathy (4.6%),
      corneal opacity (4.6%), and diabetic retinopathy (3.3%). Glaucoma (1.0%) and high
      myopia (0.39%) were minor ocular diseases among elderly Amis. The prevalence of
      diabetes was 15.4% and that of hypertension was 40.0%. CONCLUSIONS: Treatable
      diseases such as cataracts and pterygium were the most common ocular diseases in
      the Amis tribes. The relatively low incidence of glaucoma was likely due to the
      unique genetic background of this population.

PMID- 20700792
TI  - Strabismus following bilateral cataract surgery in childhood.
AB  - PURPOSE: To evaluate the clinical characteristics of strabismus in children
      undergoing bilateral cataract surgery. METHODS: We retrospectively reviewed the
      medical records of 56 children undergoing bilateral cataract surgery who had no
      evidence of strabismus before the surgery and a difference of less than two
      Snellen lines in postoperative best-corrected visual acuity between the two eyes.
      RESULTS: Strabismus developed in 31 (55.4%) patients after cataract extraction.
      Age at the time of cataract diagnosis (P = 0.006) and extraction (P = 0.025) was
      significantly lower in the strabismus group than in the no-strabismus group.
      Exotropia (45.2%) was the prevalent type of strabismus, followed by esotropia
      (35.5%). Patients with cataracts extracted within the first 12 months of life
      comprised 51.6% of the strabismus group and 20% of the no-strabismus group (P =
      0.026). Strabismus surgery was performed in 11 patients. In five aphakic patients
      with strabismus, the angle of deviation decreased significantly after secondary
      intraocular lens implantation, and strabismus surgery was not required.
      CONCLUSION: Strabismus is a frequent complication following bilateral cataract
      surgery in childhood. Children undergoing bilateral cataract surgery, especially
      at an early age, should be followed carefully for the development of strabismus.

PMID- 20700794
TI  - Twenty-four-hour ocular hypotensive effects of 0.0015% tafluprost and 0.005%
      latanoprost in healthy subjects.
AB  - PURPOSE: To compare the intraocular pressure (IOP) reduction over 24 h achieved
      with tafluprost (0.0015%) with that achieved with latanoprost (0.005%). METHODS:
      Twenty-seven healthy volunteers were studied. After a 24-h IOP baseline
      measurement was taken, one ophthalmic solution was applied to the right eye daily
      for 7 days. The drug was then withdrawn for 2 weeks. The other agent was then
      applied to the left eye in the same manner. IOP was measured every 3 h for 24 h
      on the seventh day of treatment. RESULTS: The 24-h IOP after 7 days' treatment
      with latanoprost decreased from 11.5 mmHg at baseline to 9.7 mmHg (-1.8 mmHg) and
      that with tafluprost from 11.8 to 9.8 mmHg (-1.9 mmHg). Tafluprost was
      statistically more effective after 24 h (P = 0.007; paired t test). The number of
      subjects with a 24-h mean IOP reduction of <10% was 8/27 (29.6%) with latanoprost
      versus 4/27 (14.8%) with tafluprost. The incidence of conjunctival hyperemia with
      latanoprost was 4/27 (14.8%) and that with tafluprost was 8/27 (29.6%).
      CONCLUSION: The overall efficacies of the two agents were not different, but
      tafluprost was associated with a greater reduction in IOP at 24 h after
      administration. Tafluprost showed a higher rate of conjunctival hyperemia.

PMID- 20700795
TI  - Different types of optic disc shape in patients with advanced open-angle
      glaucoma.
AB  - PURPOSE: To study the characteristics of patients with advanced open-angle
      glaucoma. METHODS: A hospital-based retrospective study was performed. Advanced
      glaucoma was defined as visual acuity of 0.3 or less, or mean deviation of -24 dB
      or less. First, we screened patients with advanced glaucoma and classified their
      glaucoma types. For patients with open-angle glaucoma (OAG), including both
      primary open-angle glaucoma (POAG) and normal-tension glaucoma (NTG), disc types
      were classified into four groups: focal ischemic (FI), myopic glaucomatous (MY),
      senile sclerotic (SS), and generalized cup enlargement (GE). RESULTS: After
      checking the medical history of 750 glaucoma patients, we classified 141 (18.8%)
      as having the advanced stage of the disease. The proportion of patients with
      advanced OAG was 47% (28% POAG, 19% NTG). The classification of optic disc
      appearances in OAG patients showed that in patients with POAG the predominant
      disc type was GE (P = 0.0012) and in those with NTG it was MY (P < 0.0001).
      CONCLUSION: In OAG patients in this study with severe glaucomatous damage, the
      predominant disc phenotype was GE in patients with POAG and MY in those with NTG.

PMID- 20700796
TI  - Localized retinal nerve fiber layer defects associated with cotton wool spots.
AB  - PURPOSE: To introduce four cases of localized retinal nerve fiber layer (RNFL)
      defects after emergence of retinal cotton wool spots (CWSs). METHODS: Four
      patients were evaluated for localized RNFL defects after the appearance of CWSs.
      Depending on the patient, they were followed up from the beginning of treatment
      to up to 19 years after the initial events. Fundus photos and other glaucoma
      examinations, including Stratus optical coherence tomography (OCT) and visual
      field examinations, were performed during the follow-up visits. RESULTS: The
      localized RNFL defects remained stable without any progression for as long as 19
      years. CONCLUSIONS: Nonprogressive RNFL defects may occur after the appearance of
      CWSs, which the examiner may not be able to detect. Clinicians may need to
      consider not only visual field results and OCT findings but also disc
      configuration, RNFL defects, and fundus findings to decide on the proper
      diagnosis and treatment of patients suspected to have glaucoma.

PMID- 20700793
TI  - Visual field loss in patients with normal-tension glaucoma under topical
      nipradilol or timolol: subgroup and subfield analyses of the nipradilol-timolol
      study.
AB  - PURPOSE: To estimate the deterioration rates of visual field loss in Japanese
      normal-tension glaucoma (NTG) patients under either topical nipradilol or
      timolol, and to explore intergroup differences in the treatment results. METHODS:
      A total of 146 NTG patients with mild to moderate damage were randomized to
      either nipradilol or timolol and followed for 3 years with a periodic
      comprehensive ophthalmological visual field examination (30-2 Humphrey perimeter
      program) every 6 months (the Nipradilol-Timolol Study). The time course of mean
      deviation (MD), the average total deviation (TD(mean)) in four subfields, and the
      corrected pattern standard deviation (CPSD) were compared between the two groups
      using regression analysis with a linear mixed effect model. RESULTS: The
      estimated slope for MD (dB/year) was -0.03 in the nipradilol and -0.05 in the
      timolol group (P > 0.4). In both groups, TD(mean) in the superior-central
      subfield and CPSD showed significant changes (-0.3 and 0.2-0.3, P <or= 0.001). In
      the patients with early visual field loss or those younger than 40 years,
      deterioration of some visual field parameters tended to be slower in the
      nipradilol group than in the timolol group. CONCLUSION: During 3 years of
      monotherapy with either nipradilol or timolol in NTG patients, only TD(mean) in
      the superior-central subfield and the CPSD changed significantly without any
      intergroup differences.

PMID- 20700797
TI  - Scanning laser ophthalmoscopic parameters of eyes with exfoliation syndrome.
AB  - PURPOSE: To evaluate optic nerve head (ONH) characteristics in patients with
      exfoliation syndrome (EXS). METHODS: This was a cross-sectional, observational
      study in which 73 eyes from 73 patients with EXS and 93 eyes from 93 age-matched
      healthy subjects who met the inclusion criteria were included. Topographic
      measurements of the ONH and peripapillary retinal nerve fiber layer (RNFL)
      thickness were performed by confocal scanning laser ophthalmoscopy, using a
      Heidelberg retina tomograph. Outcomes of interest were studied by Student t test
      and chi-squared test. RESULTS: EXS patients and age-matched controls did not
      differ in ONH parameters. Nevertheless, the mean cup depth and height variation
      contour values were higher in the normal subjects (P = 0.07, P = 0.056,
      respectively). Mean RNFL thickness was 0.22 +/- 0.06 mm in the EXS group and 0.26
      +/- 0.06 mm in the control group, (P = 0.001). Likewise, the RNFL cross-sectional
      area was significantly lower in exfoliative eyes (1.16 +/- 0.35 mm(2)) than in
      those of the control group (1.31 +/- 0.33 mm(2)) (P = 0.006). CONCLUSIONS: No
      significant differences in ONH parameters between EXS patients and age-matched
      healthy subjects were observed; however, RNFL measurements in eyes with EXS
      showed lower values.

PMID- 20700798
TI  - Optic disc analysis with Heidelberg Retina Tomography III in glaucoma with
      unilateral visual field defects.
AB  - PURPOSE: To find the optic disc features of asymmetric primary open-angle
      glaucoma. METHODS: In this observational case-control study, 52 consecutive open
      angle glaucoma patients with unilateral visual field defects participated. In
      each patient, an optic disc analysis using Heidelberg Retina Tomography III (HRT
      III) was performed. Optic disc parameters of HRT-III of eyes with abnormal visual
      fields were compared with their fellow eyes with normal visual fields. RESULTS:
      The optic disc area of the eyes with abnormal visual fields (2.35 +/- 0.55 mm(2))
      was larger than that of the fellow eyes with normal visual fields (2.25 +/- 0.43
      mm(2)) (P = 0.03). Of the eyes with abnormal visual fields, 63.5% had a larger
      optic disc area than their fellow eyes with normal visual fields. In addition, in
      the eyes with abnormal visual fields, the cup areas were larger (P = 0.000001
      0.02), whereas the rim and retinal nerve fiber layer thicknesses were thinner (P
      = 0.000002-0.036) than those of the fellow eyes with normal visual fields.
      CONCLUSIONS: The optic disc area of eyes with abnormal visual fields was larger
      than that of their fellow eyes with normal visual fields, suggesting that Chinese
      open-angle glaucoma patients with larger optic discs might be susceptible to
      glaucomatous optic damage.

PMID- 20700799
TI  - Treatment of polypoidal choroidal vasculopathy by intravitreal injection of
      bevacizumab.
AB  - PURPOSE: To evaluate the efficacy of intravitreal bevacizumab (IVB) in eyes with
      polypoidal choroidal vasculopathy (PCV). METHODS: Seventeen eyes of 16 patients
      with either subfoveal or juxtafoveal PCV were treated with IVB. As the initial
      treatment, ten eyes were treated with a single injection of bevacizumab and seven
      were treated with three monthly injections. Additional IVB injections were
      performed in 15 eyes when either a recurrent or residual exudative change was
      seen. Follow-up after initiation of IVB ranged from 12 to 30 months (mean, 20.7
      +/- 5.7 months). RESULTS: The mean foveal thickness before IVB (492 +/- 205
      microm) decreased to 384 +/- 181 microm at 3 months (P = 0.0008), and with
      additional IVB for recurrent exudative changes, the foveal thickness remained
      significantly reduced at 12 months (392 +/- 203 microm, P = 0.0270). Mean visual
      acuity at baseline (0.54 +/- 0.38 in logMAR) somewhat improved to 0.45 +/- 0.32
      at 3 months (P = 0.156). However, the improvement in visual acuity then subsided,
      and returned to the pretreatment value at 12 months (0.54 +/- 0.39). CONCLUSIONS:
      In eyes with PCV, IVB can reduce the exudative change and can maintain visual
      function for at least 1 year.

PMID- 20700800
TI  - Intravitreal bevacizumab therapy for idiopathic macular telangiectasia.
AB  - PURPOSE: To investigate the efficacy of intravitreal bevacizumab for the
      treatment of idiopathic macular telangiectasia (IMT). METHODS: Ten eyes of eight
      consecutive patients with IMT were studied. Four eyes had type 1, and six had
      type 2 IMT according to Yannuzzi's classification. All patients were treated with
      intravitreal bevacizumab (1.25 mg) injections at baseline. Monthly fundus and
      optical coherence tomography (OCT) examinations were performed. Changes in visual
      acuity, macular edema on OCT, and leakage on fluorescein angiography were
      analyzed during 6 months of follow-up. Retreatment was considered when increased
      macular edema and either fluorescein leakage or visual loss were identified.
      RESULTS: There were no changes in the mean visual acuity in either eye in any of
      the patients. In one of the four eyes with type 1 IMT, the microaneurysms
      disappeared after bevacizumab treatment. However, there were no changes in the
      other three eyes. Fluorescein leakage disappeared in four, decreased in one, and
      was unchanged in one of the eyes with type 2 IMT. An inner lamellar cyst in each
      eye was unchanged in two, newly formed in one, and expanded in one eye with type
      2 IMT. CONCLUSION: Type 2 IMT improved anatomically with bevacizumab treatment
      despite a lack of improvement in vision. Bevacizumab effectively decreases
      vascular permeability and retinal edema in the short term.

PMID- 20700801
TI  - Impact of photodynamic therapy on quality of life of patients with age-related
      macular degeneration in Korea.
AB  - PURPOSE: To assess quality of life (QOL) changes in patients with age-related
      macular degeneration (AMD) before and after treatment with photodynamic therapy
      (PDT). METHODS: In 625 patients with AMD, the EuroQol Health Questionnaire (EQ
      5D) for general health status and the Visual Function Questionnaire (VF-4D) for
      vision-related reading ability, independence, and fear for the future were used
      and the results compared between within 1 week before PDT and 1 year after PDT.
      Subscale QOL changes were also scored with the Korean versions of EQ-5D and VF
      4D. RESULTS: EQ-5D scores of male patients were higher than those of female
      patients (P < 0.05), and scores of unilateral patients were higher than those of
      bilateral patients (P < 0.001). Among all patients, 41.2% had a higher EQ-5D
      score after PDT. The mean differences between before and after treatment,
      estimated by three different models, the Korean model, the UK model, and the
      Japanese model, were all statistically significant (P < 0.001). Utility measured
      by the VF-4D score after PDT increased by 16.1% (P < 0.001), and subscale
      utilities indicated significant improvements in fear for the future (21.1%),
      reading ability (16.6%-14.5%), and independence (11.6%). CONCLUSIONS: PDT for
      patients with AMD improved both general health-related QOL and vision-related
      QOL, as well as subscale scores, as evaluated by EQ-5D and VF-4D.

PMID- 20700802
TI  - Pars plana vitrectomy with and without triamcinolone acetonide assistance in
      pseudophakic retinal detachment complicated with proliferative vitreoretinopathy.
AB  - PURPOSE: To evaluate the anatomical and functional outcomes of pars plana
      vitrectomy (PPV) in pseudophakic retinal detachment (RD) complicated with
      proliferative vitreoretinopathy (PVR) without previous scleral buckling (SB) or
      vitrectomy, both with and without triamcinolone acetonide (TA) assistance.
      METHODS: In this retrospective, interventional, comparative case series, 72
      pseudophakic eyes with RD with PVR grade C1 or greater underwent PPV either with
      (group 1, n = 40) or without (group 2, n = 32) TA assistance. Eyes with a minimum
      of 6 months of follow-up were evaluated. Main outcome measures were reattachment,
      redetachment, complication rate, and changes in visual acuity (VA). RESULTS: The
      mean follow-up period was 14.57 +/- 8.55 months. Single-surgery and final
      reattachment rates were 87.50% and 95% in group 1, and 78.12 % and 96.87% in
      group 2, (P = 0.349, P = 1.000). Redetachment rates were 12.50% in group 1 and
      21.87% group 2 (P = 0.349). In both groups the mean VA increased significantly in
      postoperative week 1 and in all control visits (P< 0.001) with no difference in
      complication rate (P > 0.05). CONCLUSIONS: In this study PPV with TA assistance
      resulted in a lower, albeit statistically insignificant, redetachment rate in the
      treatment of RD complicated with PVR compared to PPV without TA assistance in
      eyes without previous SB or PPV. Visual acuity improved in 72% of eyes in both
      groups. Intraoperative and postoperative complication rates were also similar.

PMID- 20700804
TI  - Arteritic anterior ischemic optic neuropathy with positive myeloperoxidase
      antineutrophil cytoplasmic antibody.
AB  - BACKGROUND: Myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) is
      related to smallvessel vasculitis. There have been some reports of optic nerve
      involvements with increased values of MPO-ANCA. We report two cases of anterior
      ischemic optic neuropathy (AION) in which ANCA-associated vasculitis was
      suspected to be responsible for the pathogenesis. CASES: A 66-year-old man and a
      72-year-old man had ocular symptoms of AION in both eyes with positive MPO-ANCA.
      OBSERVATIONS: Both patients showed high erythrocyte sedimentation rate, C
      reactive protein, and MPOANCA values at first. Temporal artery biopsies were
      negative for temporal arteritis, whereas small-vessel vasculitis was found only
      in the latter patient. Visual dysfunctions remained unchanged after steroid pulse
      therapy, although laboratory data returned to normal levels after the treatment.
      Fluorescein angiography revealed selective occlusion of capillaries, arterioles,
      and precapillaries in the retina and choroid as well as in the optic disc.
      CONCLUSIONS: The identical characteristics of the angiographic findings of both
      eyes in the two cases indicated that the obliteration of small vessels in the
      intraocular arterial system was closely related to MPO-ANCA-associated
      vasculitis.

PMID- 20700803
TI  - Ruthenium-106 plaque radiotherapy alone or in combination with transpupillary
      thermotherapy in the management of choroidal melanoma.
AB  - PURPOSE: To evaluate the results of ruthenium-106 (Ru-106) plaque radiotherapy
      alone (group A) or in combination with transpupillary thermotherapy (TTT) (group
      B) in the management of choroidal melanoma with tumor thickness (height) <8 mm.
      The tumors in each group were subclassified as those with thickness <or=5 mm
      versus those with thickness of >5 and <8 mm. METHODS: In this retrospective
      review, the main outcome measures were globe conservation rate, the rate of a
      reduction of at least 50% in tumor thickness, treatment complications, visual
      acuity (VA) change, and metastasis. Kaplan-Meier curves for prediction of
      decrease in tumor thickness of at least 50% over time were constructed. RESULTS:
      A total of 54 patients (24 in group A and 30 in group B) were included in this
      study. The groups were matched with respect to patient age, tumor base diameter,
      tumor thickness, tumor distance to optic disc, tumor distance to foveola, and
      baseline visual acuity (VA). The mean follow-up was 24.6 months in group A and
      44.9 months in group B. Globe conservation was achieved in 21 (87.5%) eyes in
      group A and in 26 (86.7%) eyes in group B. The globe conservation rates did not
      differ significantly between groups A and B or between tumors <or=5 mm in
      thickness and those >5 to <8 mm in thickness in each group (P > 0.05). There was
      no statistical difference between groups A and B in the rate of tumor thickness
      reduction of at least 50% (P> 0.05). There was a significant decrease in final VA
      compared to baseline VA in group B (P = 0.007) but not in group A. Radiation
      complications were similar in groups A and B. Liver metastasis occurred in two
      patients in group A and in one patient in group B. Statistical analysis could not
      be carried out for the latter two variables because of the small number of
      affected patients. CONCLUSIONS: Compared to Ru-106 plaque radiotherapy alone, Ru
      106 plaque radiotherapy combined with TTT did not result in a significant change
      in the globe conservation rate or the rate of at least 50% reduction in tumor
      thickness in choroidal melanomas <8 mm in thickness. Although Ru-106 plaque
      radiotherapy is mainly used for choroidal melanomas >or=5 mm thick, it can also
      be considered in selected tumors with thickness between 5 and 8 mm with
      comparable tumor control.

PMID- 20700805
TI  - Novel snapshot imaging of photoreceptor bleaching in macaque and human retinas.
AB  - PURPOSE: Various methods have been used to obtain a topographic map of bleached
      photopigments in human retinas in the past. The purpose of this study was to
      determine whether the bleaching topography of the photoreceptors could be
      obtained by snapshot imaging reflectometry. METHODS: Four to five fundus
      photographs of one rhesus monkey and three healthy human subjects were taken by
      white flashes at intervals of 4 s, with a commercial fundus camera with minimal
      modifications. The flash-induced reflectance increases (bleaching) were
      calculated by dividing the reflectance of the first image into the subsequent
      images, pixel by pixel. RESULTS: The topography of the bleached macula
      corresponded well with the anatomical distribution of the cones. The ratio of
      reflectance changes in the center to that in the surrounding tissue was high for
      red and low for green and blue images. These results indicate that the
      reflectivity changes were not artifacts but were derived from changes in the
      photopigment density in the cones and rods. CONCLUSIONS: The topography of
      bleached photoreceptors obtained with a commercial fundus camera from one monkey
      and three healthy human subjects showed that this technique has potential as a
      new clinical method for examining photoreceptor function in both normal and
      diseased retinas.

PMID- 20700806
TI  - Bilateral limbal stem cell deficiency with chromosomal translocation of 3p and
      9p.

PMID- 20700807
TI  - Glass fragment in the anterior chamber caused corneal endothelial dysfunction
      eight years after penetrating trauma.

PMID- 20700808
TI  - Intraocular surgery in patients receiving infliximab therapy for Behcet disease.

PMID- 20700809
TI  - Evaluation of the agreement between Pentacam and ultrasound biomicroscopy
      measurements of anterior chamber depth in Chinese patients with primary angle
      closure glaucoma.

PMID- 20700810
TI  - Leukemic glaucoma in a patient with chronic myeloid leukemia treated by
      intracameral methotrexate.

PMID- 20700811
TI  - Macular hole formation following photodynamic therapy combined with intravitreal
      injection of bevacizumab and triamcinolone acetonide.

PMID- 20700812
TI  - Secondary macular hole formation with presumed evulsion of foveal hard exudates
      in a patient with diabetic retinopathy.

PMID- 20700813
TI  - Spontaneous closure of a macular hole after vitrectomy for an epiretinal
      membrane.

PMID- 20700814
TI  - Intraocular infestation with Thelazia callipaeda.

PMID- 20700815
TI  - A case of neuromyelitis optica developing into myelitis 25 years after optic
      neuritis.

PMID- 20700816
TI  - Characterization of the solution properties of Pichia farinosa killer toxin using
      PGSE NMR diffusion measurements.
AB  - The solution behaviour with respect to pH and NaCl concentration of the tertiary
      structure and propensity for aggregation of salt- mediated killer toxin (SMKT)
      from Pichia farinosa was examined using pulsed-gradient spin-echo NMR diffusion
      measurements. It was found that in 0.15m NaCl the tertiary structure of SMKT was
      constant below pH 5.0, with the native SMKT existing as an unaggregated
      heterodimer containing the beta-subunit in a compactly folded form. However,
      above pH 5.0 the beta-subunit dissociated and lost its compact structure,
      becoming a random coil with an approximately 37% increase in effective
      hydrodynamic radius. To determine the effects of NaCl concentration on the
      tertiary structure of SMKT, diffusion measurements were performed at pH 3.5 and
      NaCl concentrations up to 2M. Both the tertiary structure and aggregation state
      of SMKT were found to be insensitive to the salt concentration which indicates
      that the activity of the toxin is not a direct result of salt-protein
      interactions.

PMID- 20700817
TI  - Analysis of deuterium relaxation-derived methyl axis order parameters and
      correlation with local structure.
AB  - Methyl axis (S2axis) and backbone NH (S2NH) order parameters derived from eight
      proteins have been analyzed. Similar distribution profiles for Ala S2axis and
      S2NH order parameters were observed. A good correlation between the two S2axis
      values of Val and Leu methyl groups is noted, although differences between order
      parameters can arise. The relation of S2axis or S2NH to solvent accessibility and
      packing density has also been investigated. Correlations are weak, likely
      reflecting the importance of collective, non-local motions in proteins. The lack
      of correlation between these simple structural parameters and dynamics emphasizes
      the importance of motional studies to fully characterize proteins.

PMID- 20700818
TI  - Heteronuclear relaxation in time-dependent spin systems: (15)N-T1 (rho)
      dispersion during adiabatic fast passage.
AB  - A novel NMR experiment comprising adiabatic fast passage techniques for the
      measurement of heteronuclear self-relaxation rates in fully 15N-enriched proteins
      is described. Heteronuclear self-relaxation is monitored by performing adiabatic
      fast passage (AFP) experiments at variable adiabaticity (e.g., variation of RF
      spin-lock field intensity). The experiment encompasses gradient- selection and
      sensitivity-enhancement. It is shown that transverse relaxation rates derived
      with this method are in good agreement with the ones measured by the classical
      Carr-Purcell-Meiboom-Gill (CPMG) sequences. An application of this method to the
      study of the carboxyl-terminal LIM domain of quail cysteine and glycine-rich
      protein qCRP2(LIM2) is presented.

PMID- 20700819
TI  - Alternative E.COSY techniques for the measurement of 3J(C (i) (') (-1),C (i)
      (beta) ) and (3) J(H (i) (N) ,C (i) (beta) ) coupling constants in proteins.
AB  - Experiments are proposed for the measurement of the vicinal coupling constants
      between beta-carbons and either amide protons of the same or carbonyl carbons of
      the preceding amino acid residue in 13C/15N-labeled proteins. Both couplings
      depend on the backbone torsional angle phi. The three-dimensional pulse sequences
      give rise to E.COSY-like multiplet patterns in which heteronuclear one-bond
      couplings separate the doublet components corresponding to the two spin states of
      the respective passive nuclei. Thus, in contrast to previously published pulse
      schemes which employed the homonuclear 1J(Calpha,Cbeta) interaction, difficulties
      due to overlap of spectral regions of active and passive spins are avoided. A
      major drawback of the novel sequences is their limited sensitivity. Nevertheless,
      application to Desulfovibrio vulgaris flavodoxin yielded coupling constants for
      more than 85% of all non-glycine and non-proline residues.

PMID- 20700820
TI  - Letter to the Editor: Sequence-specific resonance assignments for the NADP(H)
      binding component (domain III) of proton- translocating transhydrogenase from
      Rhodospisrillum rubrum.

PMID- 20700821
TI  - Automated detection of problem restraints in NMR data sets using the FINGAR
      genetic algorithm method.
AB  - The recently described FINGAR genetic algorithm method for NMR refinement [D.A.
      Pearlman (1996) J. Biomol. NMR, 8, 67-76] has been extended so that it can be
      used to detect problem restraints in an NMR-derived set of data. A problem
      restraint is defined as a restraint in a generally well-behaved set where the
      associated target value is in error, due to inaccuracies in the data,
      misassignment, etc. The method described here, FINGAR.RWF, locates problem
      restraints by finding those restraints that, if removed from the data set, result
      in a disproportionate improvement in the scoring function. The method is applied
      to several test cases of simulated data, as well as to real data for the FK506
      macrocycle, with excellent results.

PMID- 20700822
TI  - Authors index.

PMID- 20700825
TI  - Editorial.

PMID- 20700826
TI  - The three-dimensional solution structure of the SRC homology domain-2 of the
      growth factor receptor-bound protein-2.
AB  - A set of high-resolution three-dimensional solution structures of the Src
      homology region-2 (SH2) domain of the growth factor receptor-bound protein-2 was
      determined using heteronuclear NMR spectroscopy. The NMR data used in this study
      were collected on a stable monomeric protein solution that was free of protein
      aggregates and proteolysis. The solution structure was determined based upon a
      total of 1439 constraints, which included 1326 nuclear Overhauser effect distance
      constraints, 70 hydrogen bond constraints, and 43 dihedral angle constraints.
      Distance geometry-simulated annealing calculations followed by energy
      minimization yielded a family of 18 structures that converged to a root-mean
      square deviation of 1.09 A for all backbone atoms and 0.40 A for the backbone
      atoms of the central beta-sheet. The core structure of the SH2 domain contains an
      antiparallel beta-sheet flanked by two parallel alpha-helices displaying an
      overall architecture that is similar to other known SH2 domain structures. This
      family of NMR structures is compared to the X-ray structure and to another family
      of NMR solution structures determined under different solution conditions.

PMID- 20700827
TI  - Dynamics of beta-CH and beta-CH2 Groups of Amino Acid Side Chains in Proteins.
AB  - The dynamics of amino acid side chains of uniformly 13C/15N-enriched ribonuclease
      T1 (RNase T1) have been investigated. Heteronuclear longitudinal relaxation
      rates, 1H/13C NOEs, and transverse cross-correlated cross-relaxation rates
      between the Sx and the SxIz1Iz2 operators (SIIS cross relaxation) [Ernst and
      Ernst (1994) J. Magn. Reson., A110, 202-213] have been determined in this study.
      New pulse sequences for measuring the longitudinal relaxation time and the
      heteronuclear NOE of aliphatic side chain carbon nuclei were developed using the
      CCONH type of magnetization transfer and 1HN detection. In addition, an improved
      pulse sequence for the determination of the SIIS cross relaxation is presented.
      For the analysis of the relaxation rates, the model of restricted rotational
      diffusion around the chi1 dihedral angle has been applied [London and Avitabile
      (1978) J. Am. Chem. Soc., 100, 7159-7165]. These techniques were used in order to
      describe the side chain dynamics of the small globular protein RNase T1 (104
      amino acids, MW about 11 kDa). Qualitative values of microdynamical parameters
      were obtained for 73 out of 85 amino acid side chains (glycine and alanine
      residues excepted) whereas more quantitative values were derived for 67 beta-CH
      and beta-CH2 groups.

PMID- 20700828
TI  - A Spin System Labeled and Highly Resolved ed-H(CCO)NH-TOCSY Experiment for the
      Facilitated Assignment of Proton Side Chains in Partially Deuterated Samples.
AB  - The introduction of deuterated and partially deuterated protein samples has
      greatly facilitated the 13C assignment of larger proteins. Here we present a new
      version of the HC(CO)NH-TOCSY experiment, the ed-H(CCO)NH-TOCSY experiment for
      partially deuterated samples, introducing a multi-quantum proton evolution
      period. This approach removes the main relaxation source (the dipolar coupling to
      the directly bound 13C spin) and leads to a significant reduction of the proton
      and carbon relaxation rates. Thus, the indirect proton dimension can be acquired
      with high resolution, combined with a phase labeling of the proton resonances
      according to the C-C spin system topology. This editing scheme, independent of
      the CHn multiplicity, allows to distinguish between proton side-chain positions
      occurring within a narrow chemical shift range. Therefore this new experiment
      facilitates the assignment of the proton chemical shifts of partially deuterated
      samples even of high molecular weights, as demonstrated on a 31 kDa protein.

PMID- 20700829
TI  - A Sensitive Pulse Scheme for Measuring the Backbone Dihedral Angle psi Based on
      Cross-correlation Between (13)C (alpha)- (1)Halpha Dipolar and Carbonyl Chemical
      Shift Anisotropy Relaxation Interactions.
AB  - A pulse scheme for measuring cross-correlation between 13Calpha-1Halpha dipolar
      and carbonyl chemical shift anisotropy relaxation mechanisms is presented from
      which the protein backbone dihedral angle psi is measured. The method offers
      significant sensitivity gains relative to our recently published scheme for
      measuring psi based on this cross-correlation effect [Yang et al. (1997) J. Am.
      Chem. Soc., 119, 11938-11940]. The utility of the method is demonstrated with an
      application to a 42 kDa complex of 15N,13C-labeled maltose binding protein and
      beta-cyclodextrin.

PMID- 20700830
TI  - Tools for the automated assignment of high-resolution three-dimensional protein
      NMR spectra based on pattern recognition techniques.
AB  - One of the major bottlenecks in the determination of proteinstructures by NMR is
      in the evaluation of the data produced by theexperiments. An important step in
      this process is assignment, where thepeaks in the spectra are assigned to
      specific spins within specificresidues. In this paper, we discuss a spin system
      assignment tool based onpattern recognition techniques. This tool employs user
      specified 'templates'to search for patterns of peaks in the original spectra;
      these patterns maycorrespond to side-chain or backbone fragments. Multiple
      spectra willnormally be searched simultaneously to reduce the impact of noise.
      Thesearch generates a preliminary list of putative assignments, which arefiltered
      by a set of heuristic algorithms to produce the final results list.Each result
      contains a set of chemical shift values plus information aboutthe peaks found.
      The results may be used as input for combinatorialroutines, such as sequential
      assignment procedures, in place of peak lists.Two examples are presented, in
      which (i) HCCH-COSY and -TOCSY spectra arescanned for side-chain spin systems;
      and (ii) backbone spin systems aredetected in a set of spectra comprising HNCA,
      HN(CO)CA, HNCO, HN(CA)CO,CBCANH and CBCA(CO)NH.

PMID- 20700831
TI  - The effects of guanidine hydrochloride on the 'random coil' conformations and NMR
      chemical shifts of the peptide series GGXGG.
AB  - The effects of the commonly used denaturant guanidine hydrochloride(GuHCl) on the
      random coil conformations and NMR chemical shifts of theproteogenic amino acids
      have been characterized using the peptide seriesAc-Gly-Gly-X-Gly-Gly-NH(2). The
      phi angle-sensitive couplingconstants, ROESY cross peak intensities and proline
      cis-trans isomerratios of a representative subset of these peptides are
      unaffected by GuHCl,which suggests that the denaturant does not significantly
      perturb intrinsicbackbone conformational preferences. A set of(3)J(HNHalpha)
      values is presented which agreewell with predictions of recently developed models
      of the random coil. Wehave also measured the chemical shifts of all 20
      proteogenic amino acids inthese peptides over a range of GuHCl concentrations.
      The shifts exhibit alinear dependence on denaturant concentration and we report
      here correctionfactors for the calculation of 'random coil' (1)H chemicalshifts
      at any arbitrary denaturant concentration. Studies of arepresentative subset of
      peptides indicate that (13)C and(15)N chemical shifts are also perturbed by the
      denaturant.These results should facilitate the application of chemical shift
      basedanalytical techniques to the study of polypeptides in solution with
      GuHCl.The effects of the denaturant on the quality of NMR spectra and on
      chemicalshift referencing are also addressed.

PMID- 20700832
TI  - Specific (15)N, NH correlations for residues in(15) N, (13)C and fractionally
      deuterated proteins that immediately follow methyl-containing amino acids.
AB  - A triple-resonance pulse scheme is described which records(15)N, NH correlations
      of residues that immediately follow amethyl-containing amino acid. The experiment
      makes use of a(15)N, (13)C and fractionally deuterated proteinsample and selects
      for CH(2)D methyl types. The experiment isthus useful in the early stages of the
      sequential assignment process as wellas for the confirmation of backbone (15)N,
      NH chemical shiftassignments at later stages of data analysis. A simple
      modification of thesequence also allows the measurement of methyl side-chain
      dynamics. This isparticularly useful for studying side-chain dynamic properties
      in partiallyunfolded and unfolded proteins where the resolution of aliphatic
      carbon andproton chemical shifts is limited compared to that of amide nitrogens.

PMID- 20700833
TI  - Measurement of (15)N- (1)H coupling constants in uniformly (15)N-labeled
      proteins: Application to the photoactive yellow protein.
AB  - A modified HNHB experiment is presented that allows thedetermination of J(NH)
      coupling constants directly from the ratio ofcross-peak to diagonal-peak
      intensities. The experiment was applied to thephotoactive yellow protein (PYP)
      and yielded the magnitude of 117(3)J(NH(beta)) coupling constants. In addition,
      29(3)J(NH(alpha(i-1))) coupling constantscould be measured, providing information
      about the backbone angle psi.These data, in conjunction with the magnitudes of
      the(3)J(H(N)H(alpha)) coupling constantsobtained from the HNHA spectrum,
      effectively discriminate the twopossibilities for the stereospecific assignment
      of theH(alpha) resonances in glycine residues. For all eight glycineresidues in
      PYP that were not subject to conformational averaging and hadnon-degenerate
      H(alpha) resonance frequencies, the J-couplingdata, together with limited NOE
      data, yielded the stereospecific assignmentof the H(alpha) resonances for these
      residues. In addition,reliable and precise phi,psi dihedral constraints were also
      derived forthese residues from the J-coupling data.

PMID- 20700834
TI  - Overview of the pancreas.

PMID- 20700835
TI  - Physiology of the pancreas.

PMID- 20700836
TI  - Common pancreatic disease.

PMID- 20700837
TI  - Circulating RAS.

PMID- 20700838
TI  - Local RAS.

PMID- 20700839
TI  - Pancreatic RAS.

PMID- 20700840
TI  - Basic techniques for pancreatic research.

PMID- 20700841
TI  - Current research of the RAS in diabetes mellitus.

PMID- 20700842
TI  - Current research concerning the RAS in pancreatic stem cells.

PMID- 20700843
TI  - Current research of the RAS in pancreatitis and pancreatic cancer.

PMID- 20700844
TI  - Determination of melamine and its analogues in egg by gas chromatography-tandem
      mass spectrometry using an isotope dilution technique.
AB  - A method was developed for the simultaneous determination of melamine, ammeline,
      ammelide, and cyanuric acid in egg using gas chromatography-tandem mass
      spectrometry (GC-MS/MS). The samples were first extracted by the solution of
      diethylamine-water-acetonitrile (10:40:50, v/v/v). Clean-up employed an 'On Guard
      II' RP cartridge, and the dried elute was derivatised using bis
      (trimethylsilyl)trifluoroacetamide (BSTFA) with 1% trimethylchlorosilane (TMCS).
      Derivatised samples were analysed by GC-MS/MS using multiple-reaction monitoring
      (MRM) with (13)C(3)-(15)N(3)-labelled melamine and cyanuric acid as internal
      standards. Blank samples of egg were spiked with the four analytes at
      concentration level of 0.1, 0.5, 1.0 mg kg(-1), and the intra-day and inter-day
      recoveries were in the range 75.7-122.5% with the relative standard deviation
      (RSD) from 2.6% to 22.8%. Decision limits (CCalpha, alpha = 0.01) for melamine,
      ammeline, ammelide, and cyanuric acid in egg samples and milk powder were 3.5-5.9
      and 2.5 to 3.8 ug kg(-1), and the detection capabilities (CCbeta, beta = 0.05)
      were 4.9-8.4 and 3.6-9.5 ug kg(-1), respectively. The method was successfully
      applied to egg samples and milk products as well. Satisfactory results were
      obtained as part of the 2009 European Union melamine proficiency test.

PMID- 20700845
TI  - Attention-deficit/hyperactivity disorder and Williams syndrome: shared behavioral
      and neuropsychological profiles.
AB  - We compared verbally matched attention-deficit/hyperactivity disorder (ADHD),
      Williams syndrome (WS), and typically developing individuals (N = 19 each group)
      on behavioral symptoms (Conners ADHD rating scale) and neuropsychological
      functioning. Neuropsychological tasks included those that assessed short-term
      memory and executive functions from the CANTAB (Cambridge Neuropsychological Test
      Automated Battery) neuropsychological battery. Children with WS scored within the
      abnormal range and did not differ in severity from ADHD children on the Conners
      Oppositionality, Cognitive Problems/Inattention, Hyperactivity, and ADHD Index
      subscales. The WS and ADHD groups also showed similar patterns of
      neuropsychological functioning, particularly in working memory (WM) strategy use
      and delayed short-term memory (STM). The findings may have clinical implications
      for the management of individuals with WS, highlighting the potential
      significance of behavioral, educational, and pharmacological strategies and
      treatments known to be useful in the treatment of children with ADHD for
      individuals with WS.

PMID- 20700847
TI  - Effect of the organic loading rate on biogas composition in continuous
      fermentative hydrogen production.
AB  - Some systems did not select for hydrogen-producing microorganisms and an
      unexpected growth of hydrogenotrophic methanogens was observed, although the
      reactors were operated under well-defined operating conditions that could result
      in biohydrogen production. The aim of this study was to evaluate the effect of
      the organic loading rate (OLR) on the hydrogen and methane composition of the
      biogas produced in dark fermentative processes. The study was carried out using
      an upflow anaerobic sludge blanket (UASB) reactor in order to evaluate the OLR
      effect in systems with sludge retention. During continuous operation, the UASB
      reactor showed the slow development of methanogenic activity, related to the
      applied OLR. The results demonstrate that operating an UASB reactor at pH 5.5 is
      not enough to prevent the acclimation of methanogens to the acidic pH and
      therefore long-term biohydrogen production cannot be achieved. Moreover, this
      study demonstrates that OLR also has an effect on the biogas composition, where
      the higher the OLR the greater the biogas H2 content.

PMID- 20700848
TI  - In vitro copper toxicity on rabbit spermatozoa motility, morphology and cell
      membrane integrity.
AB  - In this in vitro study the effects of copper sulphate on the motility, morphology
      and structural integrity of rabbit spermatozoa were investigated. The spermatozoa
      motility was evaluated by CASA method and Annexin analysis was used for detection
      of structural changes. For analysis of morphology samples of rabbit semen were
      fixed with Hancock's solution and stained with Giemsa, and for each sample at
      least 500 spermatozoa were evaluated. The concentration of copper in the medium
      varied from 3.57 to 4.85 microg CuSO4/mL. At Time 0 the highest motility was
      detected in the control group (57.78 +/- 3.90%). Motility in groups with copper
      administration was lower in comparison to control. Significant differences were
      detected in groups with 3.70-4.85 microg CuSO4/mL (P<0.05) at Time 0. After 1 h
      of incubation with copper sulphate the motility significantly decreased almost in
      all experimental groups. However, at Time 2 h significant increase of total
      motility was observed in groups with lower concentrations of copper (3.57 and
      3.63 microg CuSO4/mL). After 24 and 48 h of incubation almost all the spermatozoa
      were dead recording no motility at all concentrations. The concentration-
      dependent decrease of spermatozoa motility up to 50% of control was detected for
      the group receiving highest copper administration (4.85 microg CuSO4/mL) at Times
      1 and 2 h. Progressive motility had an identical trend to that of motility in all
      experimental groups, at all culture times and for all concentrations. Evaluation
      of distance and velocity parameters indicated that a sort of stress tolerance
      developed in lower concentrations (3.57 and 3.63 microg CuSO4/mL). At lower
      concentrations, an increase was noted for distance parameter DCL and velocity
      parameter VCL, indirectly confirming the significant motility and progressive
      motility increase. Other motility parameters (straightness index, linearity
      index, wobble and amplitude of lateral head displacement) revealed decrease in
      the group with the highest copper concentration (4.85 microg CuSO4/mL) in
      comparison to the control group after 2 h of incubation, only. No significant
      alteration was noted for these parameters in comparison to control at Times 0 and
      1 h. The total percentage of morphologically abnormal spermatozoa was
      significantly higher (P<0.05) in the group with the highest copper concentration
      (46.20+/-5.54%) in comparison to control (30.60+/-2.91). Predominant
      morphological abnormalities were acrosomal changes, knob-twisted flagellum and
      small heads. Detection of spermatozoa with disordered membrane was carried out
      for groups with higher copper concentrations and control, using Annexin analysis.
      Analysis showed higher occurrence of positive spermatozoa in the copper-exposed
      groups. Some Annexin positive reactions from all spermatozoa were detected in the
      control group. In copper-exposed groups positive reaction proved alteration in
      anterior part of head (acrosome) and in connection segment (mid-piece) of
      spermatozoa. Detected data evidently confirm adverse effects of high copper
      sulphate concentrations in rabbit semen on parameters of spermatozoa motility,
      morphology and membrane integrity. This paper also indicates the lowest possible
      toxic concentration of copper (3.70 microg CuSO4/mL) to rabbit spermatozoa in
      relation to motility.

PMID- 20700849
TI  - Beneficial effects of oxygen addition and hybrid poplar phytoremediation of
      petroleum-contaminated soils.
AB  - Laboratory scale experiments were conducted to investigate the effect of a
      phytoremediation system using poplar trees on the smear zone-soil gases for
      petroleum hydrocarbons contaminated soil. Eight clear polyvinyl chloride (PVC)
      columns (1.5 mx0.1 m) were packed with the contaminated soil covered with clean
      top soil. Five ports were installed on the front side of each column for soil gas
      sampling. Hybrid poplar trees (Populus deltoides X nigra DN34) were grown in 4
      columns. The remaining four columns were used as controls (no trees). Three of
      the tree columns and 3 of the controls had induced air flow. An experimental
      apparatus was established to allow for the induced air to flow through the air
      flow columns. Average air flow rates of 0.43 L/d, 0.71 L/d and 1.50 L/d were
      tested. The columns were operated for 78 days. During the experiments, the effect
      of oxygen addition, through the induced air, on the development of poplar roots
      in the hydrocarbons contaminated soil was investigated. In addition, the
      compositions and concentrations of the soil gases at different soil depths were
      evaluated during the course of the experiments.

PMID- 20700850
TI  - Biomonitoring of atmospheric pollution with heavy metals in the copper mine
      vicinity located near Radovis, Republic of Macedonia.
AB  - This investigation was undertaken to determine the atmospheric pollution with
      heavy metals due to copper mining Bucim near Radovis, the Republic of Macedonia.
      Moss samples (Hyloconium splendens and Pleurozium schrebery) were used for
      biomonitoring the possible atmospheric pollution with heavy metals in mine
      vicinity. Sixteen elements (Al, As, Ba, Ca, Cd, Co, Cr, Cu, Fe, K, Mn, Na, Ni,
      Pb, Sr, and Zn) were analysed by application of flame and electrothermal atomic
      absorption spectrometry (FAAS and ETAAS) and atomic emission spectrometry with
      inductively coupled plasma (ICP-AES). The obtained values were statistically
      processed using nonparametric and parametric analysis. The median value for
      copper obtained from moss samples (10 mg kg(-1)) was much lower compared with the
      same values for the whole territory of the Republic of Macedonia (22 mg kg(-1)).
      The range of values (2.1-198 mg kg(-1)) shows much higher content of this element
      in the samples taken from the study area compared to the appropriate values for
      the whole territory of Macedonia. The association of elements As, Cd, Cu, Fe, Pb,
      and Zn was singled out by factor analysis as a characteristic anthropogenic group
      of elements. Maps of area deposition were made for this group of elements,
      wherefrom correlation of these anthropogenic born elements was confirmed.

PMID- 20700851
TI  - A conceptual approach based on suspended solids to estimate clogging time in
      constructed wetlands.
AB  - A conceptual model has been developed by using the parameter of influent
      suspended solids (SS) concentration to estimate the clogging time in constructed
      wetlands (CWs). The depth of the clogging layer is estimated through the
      effective porosity vertically along the CWs. The basis of the model to predict
      the clogging time lies in the fact that, when clogging occurs, the pore spaces
      were reduced and thus the infiltration rate was reduced. A group of laboratory
      scale CWs was employed to develop the model and validate its utilization. Good
      agreement between the experimental data and the predicted clogging time was
      obtained. This indicates that the model can be used in different operation
      conditions for estimating clogging time in CWs.

PMID- 20700852
TI  - Nutrient removal and bacterial communities in swine wastewater lagoon and
      constructed wetlands.
AB  - Surface constructed wetlands, including marsh-pond-marsh (MPM) and continuous
      marsh (CtM) were used to treat swine wastewater in this study. The objectives of
      this research were to evaluate the surface constructed wetland effects on swine
      wastewater treatment, and to investigate bacterial distribution shifts along
      treatment flows. Water quality parameters and bacterial community diversity were
      analyzed in each section of the entire wastewater treatment system, which was
      from the anaerobic lagoons (La1 and La2), through the wetlands, to the storage
      lagoon (La3) receiving wetland effluent. The results of water quality parameters
      demonstrated that the concentration of TKN, NH4+, o-PO4(3-), and COD decreased
      significantly (P<0.05) from La1 to La3. If ammonia volatilization is integrated
      for N removal in MPM wetland cell, then there was no difference between MPM and
      CtM cells. The total bacterial community in each section of the system was
      examined by using PCR-DGGE (polymerase chain reaction-denaturing gradient gel
      electrophoresis) technique. Our finding disclosed that the bacterial communities
      in different sections of the wastewater treatment system showed high diversities.
      The bacterial community compositions shifted gradually with the wastewater
      treatment procedure. Principal component analysis (PCA) and redundancy analysis
      (RDA) confirmed that the bacterium species distribution was strongly related to
      the COD, o-PO4(3-), and TKN concentrations, whereas moderately related to the
      NH4+ concentration. Flavobacterium sp. and Methylomonas sp. were detected
      according to partial 16S rRNA gene sequences.

PMID- 20700853
TI  - Coach strategies for addressing psychosocial challenges during the return to
      sport from injury.
AB  - The purpose of this study was to examine coach strategies for addressing
      athletes' psychosocial challenges in returning to sport following injury
      rehabilitation. Qualitative interviews with eight elite coaches from the Western
      Australian Institute of Sport (WAIS) in Perth, Australia revealed that coaches
      facilitated athletes' return to sport from injury through a variety of means, but
      did not typically provide systematic forms of assistance. Coaches commented that
      the idiosyncratic nature of the injury experience meant that they needed to apply
      strategies consistent with athletes' particular psychosocial needs. Such
      strategies included: (a) coordination of a "team approach" to rehabilitation; (b)
      fostering open communication with athletes and treatment team members; (c) social
      support; (d) positive thinking and goal setting; and (e) role models. Analysis of
      these strategies revealed that coaches attempted to address competence, autonomy,
      and relatedness needs in facilitating athletes' return from injury. These
      findings suggest that self-determination theory may be a valuable approach for
      examining coach forms of assistance regarding athletes' return to competition
      following injury. Findings are discussed in relation to injury literature and
      self-determination theory. Suggestions for future research are also presented.

PMID- 20700854
TI  - Sex differences in the relationship between aggressiveness and the strength of
      handedness in humans.
AB  - Cerebral lateralisation, the partitioning of cognitive functioning into one
      hemisphere of the brain, was once considered unique to humans; however, recent
      research in a variety of taxa suggests that lateralisation is an evolutionarily
      ancient adaptation. Handedness is the most obvious manifestation of cerebral
      lateralisation in humans. Much of the literature on handedness has focused on the
      direction, rather than the strength, of this lateralisation. From both genetic
      and evolutionary perspectives it may be more informative to study degrees of
      cerebral lateralisation rather than direction. Strong evidence suggests that the
      strength may be more closely associated with individual differences in behaviour
      in humans than the direction, and individual variation in the degree of
      lateralisation has been found to correlate with personality-like characteristics
      such as aggressiveness in fish. The association between different patterns of
      lateralisation and personality characteristics may help explain how variation in
      the strength of lateralisation is evolutionarily stable in natural populations.
      The present study investigated the relationship between aggression and strength
      of handedness in humans. We found a significant interaction between sex and
      lateralisation with respect to aggression. In males, trait aggression was
      significantly higher in strong-handers than in mixed-handers, while no difference
      was seen in females. This finding highlights the importance of considering sex as
      a factor when investigating relationships between cerebral lateralisation and
      personality characteristics. Potential causes and consequences of the sex
      interaction as well as future directions for research are discussed.

PMID- 20700858
TI  - Improving college students' evaluation of text learning using idea-unit
      standards.
AB  - When recalling key definitions from class materials, college students are often
      overconfident in the quality of their responses. Even with commission errors,
      they often judge that their response is entirely or partially correct. To further
      understand this overconfidence, we investigated whether idea-unit judgements
      would reduce overconfidence (Experiments 1 and 2) and whether students inflated
      their scores because they believed that they knew answers but just responded
      incorrectly (Experiment 2). College students studied key-term definitions and
      later attempted to recall each definition when given the key term (e.g., What is
      the availability heuristic?). All students judged the quality of their recall,
      but some were given a full-definition standard to use, whereas other students
      first judged whether their response included each of the individual ideas within
      the corresponding correct answer. In Experiment 1, making these idea-unit
      judgements reduced overconfidence for commission errors. In Experiment 2, some
      students were given the correct definitions and graded other students' responses,
      and some students generated idea units themselves before judging their responses.
      Students were overconfident even when they graded other students' responses, and,
      as important, self-generated idea units for each definition also reduced
      overconfidence in commission errors. Thus, overconfidence appears to result from
      difficulties in evaluating the quality of recall responses, and such
      overconfidence can be reduced by using idea-unit judgements.

PMID- 20700859
TI  - Do the effects of subjective frequency and age of acquisition survive better word
      frequency norms?
AB  - Megastudies with processing efficiency measures for thousands of words allow
      researchers to assess the quality of the word features they are using. In this
      article, we analyse reading aloud and lexical decision reaction times and
      accuracy rates for 2,336 words to assess the influence of subjective frequency
      and age of acquisition on performance. Specifically, we compare newly presented
      word frequency measures with the existing frequency norms of Kucera and Francis
      (1967), HAL (Burgess & Livesay, 1998), Brysbaert and New (2009), and Zeno, Ivens,
      Millard, and Duvvuri (1995). We show that the use of the Kucera and Francis word
      frequency measure accounts for much less variance than the other word
      frequencies, which leaves more variance to be "explained" by familiarity ratings
      and age-of-acquisition ratings. We argue that subjective frequency ratings are no
      longer needed if researchers have good objective word frequency counts. The
      effect of age of acquisition remains significant and has an effect size that is
      of practical relevance, although it is substantially smaller than that of the
      first phoneme in naming and the objective word frequency in lexical decision.
      Thus, our results suggest that models of word processing need to utilize these
      recently developed frequency estimates during training or setting baseline
      activation levels in the lexicon.

PMID- 20700860
TI  - Fetal and neonatal alloimmune thrombocytopenia: harvesting the evidence to
      develop a clinical approach to management.
AB  - Neonatal alloimmune thrombocytopenia (NAIT) is the most common cause of severe
      thrombocytopenia in an otherwise healthy newborn. The most serious complication
      is intracranial hemorrhage, which can occur either in the fetus or the newborn.
      Despite the known serious sequelae, both antenatal management and neonatal
      treatment modalities are plagued by the lack of gold standard evidence to
      appropriately direct therapy. Maternal, risk-based therapeutic approaches range
      from invasive protocols to relatively benign noninvasive strategies to avoid
      serious procedural complications. Intravenous immunoglobulin (IVIG) with or
      without steroids and fetal blood sampling constitute the mainstay of antenatal
      management. Neonatal interventions principally focus on the use of antigen
      negative compatible or random donor platelets and IVIG. While awaiting the
      results of controlled trials, each institution must develop a standardized,
      collaborative, multidisciplinary approach to the screening, diagnostic
      evaluation, and management of unexpected and anticipated NAIT based on
      experience, product availability, and emerging scientific data.

PMID- 20700861
TI  - The professional imperative for obstetrician-gynecologists to discontinue newborn
      male circumcision.
AB  - Newborn male circumcision has been practiced for millennia for a variety of
      medical, social, religious, and cultural reasons. Indications for routine
      circumcision remain controversial, with proponents and dissidents arguing their
      sides vigorously. Popular in the United States, it has persisted in the scope of
      practice of obstetrics and gynecology, a field specializing in the opposite
      gender. To excel in women's reproductive health, we should no longer passively
      accept or actively maintain this procedure in our specialty. Steps are suggested
      to remove the residual and improper inclusion of circumcision from the scope of
      practice of obstetrics and gynecology.

PMID- 20700862
TI  - Clinical course of symptomatic spontaneous pneumothorax in term and late preterm
      newborns: report from a large cohort.
AB  - The purpose of this observational study was to characterize the clinical course
      of newborn infants with spontaneous pneumothorax and to identify those infants
      who eventually required further interventions. We performed a retrospective
      review of newborns with symptomatic spontaneous pneumothorax, born between
      January 2002 and December 2007. Seventy-six infants >=36 weeks' gestation were
      identified with symptomatic spontaneous pneumothorax. Twenty-two (29%) of the 76
      infants with spontaneous pneumothorax required either thoracentesis or/and
      thoracostomy drainage, and 54 (71%) were managed without such intervention. In
      all, 18 (24%) infants received mechanical ventilation and 12 (16%) infants
      developed persistent pulmonary hypertension (PPHN) during the course of illness.
      Ten of the 22 infants requiring thoracentesis and/or thoracostomy for
      progressively worsening respiratory distress developed PPHN. Seven of these 10
      infants with PPHN received inhaled nitric oxide, and four infants subsequently
      required extracorporeal membrane oxygenation. In contrast, the majority of the
      infants (50 of 54, 93%) not requiring thoracentesis or/and thoracostomy could be
      managed simply with supplemental oxygen or close observation. Progressively
      worsening respiratory distress prompting intervention in infants with spontaneous
      pneumothorax may indicate presence of PPHN that needs prompt recognition and
      referral to tertiary-level neonatal units for escalating respiratory support.

PMID- 20700863
TI  - An observational study of early neonatal biochemical parameters in twins.
AB  - Early neonatal biochemical values are generally considered to reflect maternal
      values. However, studies have been inconclusive due to the statistical methods
      used. We hypothesized that there would not be important differences in plasma
      biochemistry between newborn twins, suggesting a common mechanism of control, and
      that differences between unrelated infant pairs would be greater. All twins over
      a 5-year period who had plasma biochemistry measured within 6 hours of birth were
      identified retrospectively. An unrelated control infant was matched to one of
      each twin pair. The 95% limits of agreement for plasma urea, creatinine, and
      sodium were calculated for twin pairs and unrelated matched infant pairs. Fifty
      three twin pairs were studied. For urea, creatinine, and sodium, 95% of
      differences between twins were less than or equal to 1.5 mmol/L (8.9 mg/dL), 9.2
      MUmol/L (0.1 mg/dL), and 5.1 mmol/L (11.7 mg/dL), respectively. In unrelated
      infant pairs, the corresponding values were 4.0 mmol/L (24.3 mg/dL), 33.9 MUmol/L
      (0.4 mg/dL), and 8.2 mmol/L (18.9 mg/dL). Differences between unrelated infant
      pairs were significantly wider than differences between twins ( p < 0.001). This
      study has demonstrated a close and significant agreement in urea, sodium, and
      creatinine when measured soon after birth in twin pairs compared with unrelated
      infants, implying a common mechanism of control.

PMID- 20700864
TI  - Endothelin-1 and L-arginine in preterm infants with respiratory distress.
AB  - In addition to the immaturity of air sacs and surfactant deficiency, preterm
      infants with respiratory distress syndrome (RDS) have abnormalities in the
      pulmonary vascular bed. We aimed to study two known modulators of pulmonary
      vessels: endothelin-1 (ET-1) and L-arginine. We hypothesized that plasma
      concentrations of ET-1 and L-arginine could correlate with the severity of RDS.
      We prospectively studied 71 preterm infants (gestational age = 29 to 35 weeks)
      with and without RDS. We measured plasma ET-1 by enzyme-linked immunosorbent
      assay and L-arginine by spectrophotometry. Infants who continued to require
      oxygen support or died by day of life 28 were considered to have bronchopulmonary
      dysplasia (BPD). ET-1 concentrations were significantly higher in RDS infants ( p
      = 0.039) than controls. Among infants with RDS, it was significantly higher in
      those who later developed BPD ( p = 0.026). L-arginine was significantly lower in
      RDS infants ( p = 0.001), but did not differ between BPD and non-BPD infants ( p
      = 0.19). There was no correlation between L-arginine and ET-1 ( r = 0.1, p =
      0.41). The acute phase of RDS is associated with increased plasma concentrations
      of ET-1 and decreased L-arginine. Infants who later developed BPD had higher
      plasma ET-1 at birth. Concentrations of ET-1 and L-arginine did not correlate.

PMID- 20700865
TI  - Clinical value of the 11- to 13+6-week sonogram for detection of congenital
      malformations: a review.
AB  - We sought to determine the clinical value of the 11- to 13(+6)-week ultrasound
      evaluation for diagnosis of congenital abnormalities. A literature search was
      conducted for publications concerning the use of the 11- to 13(+6)-week
      ultrasound evaluation for prenatal diagnosis of congenital abnormalities. Series
      with more than 1000 cases published in the English language were selected. The
      reported data were integrated and a pooled analysis was performed to provide
      meaningful clinical interpretations. Our analysis of data from 36,237 pregnancies
      generated by eight centers suggests that the overall detection rate of major
      congenital anomalies during the 11- to 13(+6)-week ultrasound evaluation is 29%
      (95% confidence interval 25 to 33). Prenatal diagnosis at these stages of
      development could improve if evaluations are implemented in accordance to very
      well delineated protocols.

PMID- 20700868
TI  - Mammographic features of the sternalis muscle.
AB  - PURPOSE: To evaluate the mammographic findings of the sternalis muscle and
      discuss appropriate diagnostic approaches. MATERIALS AND METHODS: Ten years of
      records from our mammography unit were retrospectively examined for the presence
      of the sternalis muscle. This variant was seen in 10 women out of the 52,930
      examined, and the mammograms of these patients were reevaluated. The size, shape
      and contours of the muscle were reviewed on the craniocaudal (CC) and
      mediolateral oblique (MLO) views. Yearly mammograms were assessed to evaluate
      follow-up changes. Extra examinations were reviewed, including ultrasound (US),
      computed tomography (CT) and magnetic resonance imaging (MRI). RESULTS: The
      prevalence of the sternalis muscle was 0.018%. Its contours were well-defined,
      irregular or spiculated, and the diameter ranged from 3-4 mm to 15 mm. The shape
      of the muscle varied from slightly bulging to round or triangular. The muscle was
      detected on MLO projections in three patients as an inferior soft tissue density
      at the posterior edge of the breast, continuous with the pectoralis muscle.
      Distinct pulling of the breast led to variations in the appearance of the muscle
      on yearly mammograms. US examinations were normal in all patients. CT and MRI
      showed the muscle clearly. CONCLUSION: The appearance of the sternalis muscle may
      vary on CC views. It may also be detected on MLO projections. The ability to
      visualize the muscle depends on proper positioning. Knowledge of its
      detectability on mammograms will prevent the misdiagnosis of a mass and prevent
      further unnecessary investigations.

PMID- 20700870
TI  - [CME-ECG -- status after cardiac surgical intervention].

PMID- 20700869
TI  - [Acute abdominal pain].

PMID- 20700871
TI  - [Motor recovery after spinal cord injury: assessments, factors and mechanisms].
AB  - The recovery of motor functions after a spinal cord injury (SCI) can be assessed
      at the domain of body-functions and structures and activities. As there is no
      gold standard for quantifying motor functions, the recovery depends strongly on
      the assessment applied. After a motor complete SCI, the improvement in activities
      of daily life is larger as would be expected from the increase in muscle strength
      alone. After a motor incomplete SCI, the (prolonged) latency of the motor evoked
      potential remains stable, while considerable improvements in muscle strength,
      walking capacity and independence can be observed. Such functional recovery is
      based on compensational mechanisms and neuroplasticity.

PMID- 20700872
TI  - [Cataract surgery - essentials for the general practitioner].
AB  - Age-related cataracts are mainly caused by life-long accumulation of oxidative
      stress on the lens fibres. Symptoms include reduced visual acuity, requiring more
      light for reading, and glare. The only treatment that provides a cure for
      cataracts is surgery. Phacoemulsification represents the preferred method of lens
      removal. It involves fragmentation of the lens using ultrasound and insertion of
      an artificial intraocular lens. The preoperative assessment the general
      practitioner provides to surgeon and anesthesia team has an important share in
      the low complication rate of the procedure in the event of co-existing systemic
      disease. Growing patient expectation for spectacle independence following
      cataract surgery is met to some extent using techniques for astigmatism control
      and presbyo-pia-correcting intraocular lenses.

PMID- 20700873
TI  - [Decreasing the venous thromboembolism risk Summary of the NICE guidelines].

PMID- 20700874
TI  - [Persistent neutropenia].
AB  - We report the case of a 72-old patient with persistent neutropenia diagnosed
      during investigation of sialadenitis. Further examination led to the diagnosis of
      immune neutropenia and systemic lupus erythematosus. Anamnesis and the clinical
      course made initial diagnosis of drug-induced lupus erythematosus implausible.
      Steroid trial was done, followed by maintenance therapy, with good control of
      symptoms.

PMID- 20700877
TI  - [Answers to the questions on thrombocytopenia from PRAXIS No. 15].

PMID- 20700878
TI  - [CME - Ultrasonography 35/Solution -- Cough, fever, chest pain (and case
      history)].

PMID- 20700879
TI  - [Physicians -- literature riddle].

PMID- 20700880
TI  - [The physicians' art column. You never walk alone].

PMID- 20700881
TI  - Stimuli-sensitive polymers.

PMID- 20700886
TI  - Recovering Ga(III) from coordination complexes using pyridine 2,6-dicarboxylic
      acid chelation ion chromatography.
AB  - Ion exchange chelation chromatography is an effective means to extract metals
      from coordination complexes and biological samples; however there is a lack of
      data to verify the nature of metal complexes that can be successfully analysed
      using such a procedure. The aim of this study was to assess the capability of
      pyridine 2,6-dicarboxylic acid (PDCA) to extract and quantify Ga(III) from a
      range of environments using standard liquid chromatography apparatus. The PDCA
      chelation method generated a single Ga(III) peak with a retention time of 2.55 +/
      0.02 min, a precision of <2% and a limit of detection of 110 microM. Ga(III)
      hydroxide complexes (highest stability constant 15.66) were used to successfully
      cross-validate the chelation method with inductively coupled plasma mass
      spectrometry. The PDCA assay extracted 96.9 +/- 1.2% of the spiked Ga(III) from
      porcine mucus and 100.7 +/- 2.7% from a citrate complex (stability constant
      10.02), but only ca 50% from an EDTA complex (stability constant 22.01). These
      data suggest that PDCA chelation can be considered a suitable alternative to
      inductively coupled plasma mass spectrometry for Ga(III) quantification from all
      but the most strongly bound coordinated complexes i.e. a stability constant of
      <15.

PMID- 20700887
TI  - History of studies on mammalian middle ear evolution: a comparative morphological
      and developmental biology perspective.
AB  - The mammalian middle ear represents one of the most fundamental morphological
      features that define this class of vertebrates. Its skeletal pattern differs
      conspicuously from those of other amniotes and has attracted the attention of
      comparative zoologists for about 200 years. To reconcile this morphological
      inconsistency, early comparative morphologists suggested that the mammalian
      middle ear was derived from elements of the jaw joint of nonmammalian amniotes.
      Fossils of mammalian ancestors also implied a transition in skeletal morphology
      that resulted in the mammalian state. During the latter half of the 20th century,
      developmental mechanisms controlling the formation of the jaw skeleton became the
      subject of studies in developmental biology and molecular genetics. Mammalian
      middle ear evolution can now be interpreted as a series of changes in the
      developmental program of the pharyngeal arches. In this review, we summarize the
      history of middle ear research, highlight some of the remaining problems, and
      suggest possible future directions. We propose that to understand mammalian
      middle ear evolution, it is essential to identify the critical developmental
      events underlying the particular mammalian anatomy and to describe the
      evolutionary sequence of changes in developmental and molecular terms. We also
      discuss the degree of consistency between the developmental explanation of the
      mammalian middle ear based on molecular biology and morphological changes in the
      fossil record.

PMID- 20700888
TI  - Developmental plasticity links local adaptation and evolutionary diversification
      in foraging morphology.
AB  - Developmental plasticity is thought to reconcile the constraining role of natural
      selection in maintaining local adaptation with evolutionary diversification under
      novel conditions, but empirical documentations are rare. In vertebrates, growth
      and development of bones is partially guided by contractions of attached
      musculature and such muscle activity changes progressively through embryonic
      development from sporadic motility to direct functional effects. In species with
      short generation times, delayed skull maturation extends the guiding effects of
      muscle activity on formation of foraging morphology into adulthood, providing an
      opportunity to directly examine the links between plasticity of bone development,
      ecological adaptations, and evolutionary diversification in foraging morphology.
      In this case, the morphological consequences of inputs due to local functional
      requirements should be evident in adaptive divergence across taxa. Here we
      provide evidence that epigenetic regulation of bone growth in Soricid shrews may
      enable both development of local adaptations and evolutionary divergence in
      mandibular morphology. We contrast the effects of muscle stimulation on early-
      vs. late-maturing components of, foraging apparatus to show that the morphology
      of late-maturing components is more affected by functional requirements than are
      early-ossifying traits. Further, the divergence in foraging morphology across
      shrew species occurs along the directions delineated by inductive effects of
      muscle loading and bite force on bone formation in late-maturing but not early
      maturing mandible components within species. These results support the hypothesis
      that developmental plasticity can link maintenance of local adaptations with
      evolutionary diversification in morphology.

PMID- 20700889
TI  - Speciation of polyploid Cyprinidae fish of common carp, crucian carp, and silver
      crucian carp derived from duplicated Hox genes.
AB  - Recent studies on comparative genomics have suggested that a round of fish
      specific whole genome duplication (3R) in ray-finned fishes might have occurred
      around 226-316 Mya. Additional genome duplication, specifically in cyprinids, may
      have occurred more recently after the divergence of the teleosts. The timing of
      this event, however, is unknown. To address this question, we sequenced four Hox
      genes from taxa representing the polyploid Cyprinidae fish, common carp (Cyprinus
      carpio, 2n=100), crucian carp (Carassius auratus auratus, 2n=100), and silver
      crucian carp (C. auratus gibelio, 2n=156), and then compared them with known
      sequences from the diploid Cyprinidae fish, blunt snout bream (Megalobrama
      amblycephala, 2n=48). Our results showed the presence of two distinct Hox
      duplicates in the genomes of common and crucian carp. Three distinct Hox
      sequences, one of them orthologous to a Hox gene in common carp and the other two
      orthologous to a Hox gene in crucian carp, were isolated in silver crucian carp,
      indicating a possible hybrid origin of silver crucian carp from crucian and
      common carp. The gene duplication resulting in the origin of the common ancestor
      of common and crucian carp likely occurred around 10.9-13.2 Mya. The speciations
      of common vs. crucian carp and silver crucian vs. crucian carp likely occurred
      around 8.1-11.4 and 2.3-3.0 Mya, respectively. Finally, nonfunctionalization
      resulting from point mutations in the coding region is a probable fate for some
      Hox duplicates. Taken together, these results suggested an evolutionary model for
      polyploidization in speciation and diversification of polyploid fish.

PMID- 20700890
TI  - Possibility of mixed progenitor cells in sea star arm regeneration.
AB  - In contrast to most vertebrates, invertebrate deuterostome echinoderms, such as
      the sea star Asterias rubens, undergo regeneration of lost body parts. The
      current hypothesis suggests that differentiated cells are the main source for
      regenerating arm in sea stars, but there is little information regarding the
      origin and identity of these cells. Here, we show that several organs distant to
      the regenerating arm responded by proliferation, most significantly in the
      coelomic epithelium and larger cells of the pyloric caeca. Analyzing markers for
      proliferating cells and parameters indicating cell ageing, such as levels of DNA
      damage, pigment, and lipofuscin contents as well as telomere length and
      telomerase activity, we suggest that cells contributing to the new arm likely
      originate from progenitors rather than differentiated cells. This is the first
      study showing that cells of mixed origin may be recruited from more distant
      sources of stem/progenitor cells in a sea star, and the first described
      indication of a role for pyloric caeca in arm regeneration. Data on growth rate
      during arm regeneration further indicate that regeneration is at the expense of
      whole animal growth. We propose a new working hypothesis for arm regeneration in
      sea stars involving four phases: wound healing by coelomocytes, migration of
      distant progenitor cells of mixed origin including from pyloric caeca,
      proliferation in these organs to compensate for cell loss, and finally, local
      proliferation in the regenerating arm.

PMID- 20700891
TI  - From fetus to adult--an allometric analysis of the giraffe vertebral column.
AB  - As mammalian cervical vertebral count is almost always limited to seven, the
      vertebral column of the giraffe (Giraffa camelopardalis) provides an interesting
      study on scaling and adaptation to shape in light of these constraints. We have
      defined and described the growth rates of the lengths, widths, and heights of the
      vertebrae from fetal through neonatal life to maturity. We found that the
      disproportionate elongation of the cervical vertebrae is not a fetal process but
      occurs after birth, and that each cervical (C2-C7) vertebrae elongates at the
      same rate. C7 is able to specialize toward elongation as its function has been
      shifted to T1. We concluded that T1 is a transitional vertebra whose scaling
      exponent and length is between that of the cervical and thoracic series. Despite
      its transitional nature, T1 is still regarded as thoracic, as it possesses an
      articulating rib that attaches to the sternum. The other dimensions taken (width,
      height, and spinous process length) show that giraffe vertebral morphology
      exhibit adaptations to biomechanical strain, and we have underlined the
      importance of the thoracic spinous processes in supporting the head and neck.

PMID- 20700892
TI  - Alternative processing of scrambled genes generates protein diversity in the
      ciliate Chilodonella uncinata.
AB  - In ciliates, chromosomal rearrangements occur during the development of the
      somatic macronuclear genome from the germline micronuclear genome. These
      rearrangements are extensive in three ciliate classes-Armophorea, Spirotrichea,
      and Phyllopharyngea-generating a macronucleus with up to 20,000,000 gene-sized
      chromosomes. Earlier, we have shown that these three classes also share elevated
      rates of protein evolution relative to other ciliates. To assess the evolution of
      germline-limited sequences in the class Phyllopharyngea, we used a combination of
      traditional and walking PCR to analyze micronuclear copies of multiple genes from
      two lines of the morphospecies Chilodonella uncinata for which we had previously
      characterized macronuclear sequences. Analyses of the resulting data yield three
      main results: (1) conserved macronuclear (somatic) regions are found within
      rapidly evolving micronuclear (germline) regions; (2) gene scrambling exists
      within this ciliate lineage; and (3) alternative processing of micronuclear
      regions yields diverse macronuclear beta-tubulin paralogs. To our knowledge, this
      is the first study to demonstrate gene scrambling outside the nonsister class
      Spirotrichea, and to show that alternative processing of scrambled genes
      generates diversity in gene families. Intriguingly, the Spirotrichea and
      Phyllopharyngea are also united in having transient "giant" polytene chromosomes,
      gene-sized somatic chromosomes, and elevated rates of protein evolution. We
      hypothesize that this suite of characters enables these ciliates to enjoy the
      benefits of asexuality while still maintaining the ability to go through sexual
      cycles. The data presented here add to the growing evidence of the dynamic nature
      of eukaryotic genomes within diverse lineages across the tree of life.

PMID- 20700893
TI  - Embryonic development of Ampheres leucopheus and Iporangaia pustulosa (Arachnida:
      Opiliones: Gonyleptidae).
AB  - The first studies concerning the embryonic development of harvestmen started in
      the late 19th century, and focused mostly on holarctic species, and only three
      species of the suborder Laniatores (the largest, among the four suborders
      considered presently) were studied. Moreover, the last studies on embryology of
      harvestmen were made during the late 1970s. This study focused on the embryonic
      development of Ampheres leucopheus (Gonyleptidae, Caelopyginae) and Iporangaia
      pustulosa (Gonyleptidae, Progonyleptoidellinae). The embryonic development was
      followed in the field, by taking daily photographs of different eggs during about
      2 months. When laid, eggs of A. leucopheus and I. pustulosa have approximately
      1.13 and 1.30 mm in diameter, respectively, and the second is embedded in a large
      amount of mucus. The eggs grow, mainly due to water absorption at the beginning
      of the process, and they reach a diameter of about 1.35 and 1.59 mm,
      respectively, close to hatching. It took, respectively, 29-56 days and 35-66 days
      from egg laying to hatching. For the description of the embryonic development, we
      use photographs from the field, SEM micrographs, and histological analysis. This
      allowed us, for instance, to document the progression of structures and
      pigmentation directly from live embryos in the field, and to record
      microstructures, such as the presence of perforations in the cuticle of the
      embryo in the place where eyes are developing. Yet, contrary to what was expected
      in the literature, we record an egg tooth in one of the studied laniatoreans.

PMID- 20700897
TI  - Genetics: Gene-expression profiling in leukemia--a valuable diagnostic tool.

PMID- 20700894
TI  - Molecular characterization of the Bidder's organ in the cane toad (Bufo marinus).
AB  - In toads, both males and females develop a unique gonadal structure called the
      Bidder's organ (BO), which resembles ovarian tissue and is attached to the
      anterior part of the gonad. It is not clear whether the BO is a vestigial organ,
      or has an endocrine function. In this study, we investigated the expression of
      the gonadal development genes Dmrt1, Sox9, Sf1, Dax1, and p450arom in the
      developing BO as compared with the gonads of male and female cane toads. We
      demonstrate that Sf1, Dax1, and p450arom, key genes involved in vertebrate
      steroidogenesis, are transcriptionally active in the BO during developmental
      milestones associated with sexual development and maturation. Furthermore, the
      pattern of transcriptional activity in the BO is completely independent of the
      corresponding gonads in both sexes, despite its ovary-like morphology. These
      results suggest that the BO likely has a steroidogenic role in the development of
      the cane toad, distinct from that of the gonads.

PMID- 20700898
TI  - Targeted therapies: Activated PI3K/AKT confers resistance to trastuzumab but not
      lapatinib.

PMID- 20700899
TI  - Coma in a 34-year-old with progressive changes on neuroimaging.

PMID- 20700900
TI  - An unusual cause of headache and nasal discharge in a 40-year-old female.

PMID- 20700901
TI  - Standardized ultrasound protocol, trained sonographers and digital system for
      carotid atherosclerosis screening.
AB  - BACKGROUND AND PURPOSE: Carotid intima-media thickness (IMT), a valid measure of
      atherosclerotic disease, has been proposed to be included in the algorithms for
      cardiovascular risk stratification. However, assessment of carotid IMT is still
      not easily performed in an office setting. In the present study, we evaluated the
      reproducibility of a standardized protocol for carotid artery atherosclerosis
      screening. METHODS: Carotid arteries of 30 patients were scanned twice (interval
      1-10 days) by six trained sonographers, using portable ultrasound systems. A
      screening protocol was adapted from methods used in clinical trials in which
      carotid IMT was the primary outcome measure. To test the reproducibility of the
      method, variability between the two scans was analyzed. RESULTS: A high level of
      agreement was found between the scans for measurement of mean common carotid IMT
      [mean difference S0.002, 95% confidence interval (CI) S0.011 to 0.006, PU0.435],
      maximum region common carotid IMT (mean difference S0.002, 95% CIS0.017 to 0.014,
      PU0.779) and mean maximum IMT including the common, bifurcation and internal
      carotid arteries (mean differences 0.021, 95% CI S0.006 to 0.047, PU0.166). No
      significant differences were found between scans with regard to the average
      number of carotid segments visualized, the number of atherosclerotic plaques or
      plaque burden. CONCLUSION: Reliable IMT measurements can be obtained using a
      standardized protocol performed by trained sonographers using a digital portable
      ultrasound system in an office setting.

PMID- 20700902
TI  - Future challenges for microsomal transport protein inhibitors.

PMID- 20700904
TI  - Proceedings of the Third Parenteral Drug Association Workshop on Mycoplasmas.
      Berlin, Germany. March 24-26, 2009.

PMID- 20700903
TI  - [Purposeful diagnosis and optimal therapy: management of invasive mycoses-a
      constant challenge. Proceedings of the 7th Workshop. Berlin, Germany. March 13
      14, 2010. Dedicated to Professor Hannelore Bernhardt on her 75th birthday].

PMID- 20700905
TI  - Proceedings from the 9th Asia Pacific Biochemical Engineering Conference
      (APBioChEC), Kobe, Japan, November 24-28, 2009.

PMID- 20700906
TI  - Donors lose faith in Zambian Health Ministry.

PMID- 20700907
TI  - UN Women to spearhead new drive for gender equality.

PMID- 20700908
TI  - Psychological trauma Victorian style: from perpetrators to victims.

PMID- 20700909
TI  - Characterization of murine brain membrane glycoproteins by detergent assisted
      lectin affinity chromatography.
AB  - Membrane glycoproteins play vital roles in many fundamental physiological and
      pathophysiological processes in the central nervous system and represent
      important targets for pharmaceuticals and biomarker discovery. However, their
      isolation and characterization have been greatly limited. Lectin affinity
      chromatography (LAC) has evolved as a powerful method to enrich glycoproteins in
      biofluid and cell/tissue lysate. However, its use in the hydrophobic fraction of
      the samples has rarely been explored. In this study, we have conducted a
      systematic investigation on the lectin binding efficiency in the presence of four
      commonly used detergents. We have found that, under certain concentrations,
      detergents can minimize nonspecific binding and facilitate the elution of
      hydrophobic glycoproteins. With the detergent assisted lectin affinity
      chromatography (DALAC), a total of 1491 proteins were identified with low numbers
      of false positives from two lectins. Proteins (699) were identified with at least
      two unique peptides, of which 219 are membrane glycoproteins. Compared to the
      traditional methods, the DALAC approach significantly increased the recovery of
      plasma membrane and glycoproteins. NP-40 is recommended as a well rounded
      detergent for DALAC, but the conditions for enriching certain target proteins
      need to be empirically determined. This study represents the first global
      identification of the murine brain glycoproteome.

PMID- 20700910
TI  - Proceedings of the 10th Meeting of the Plant Oxygen Group. July 8-10, 2009.
      Helsinki, Finland.

PMID- 20700911
TI  - Quantification in gas chromatography: prediction of flame ionization detector
      response factors from combustion enthalpies and molecular structures.
AB  - In a previous report, we validated the use of a database that compiled the
      relative response factors of flavor and fragrance compounds under standard GC
      conditions for a flame ionization detector. Here we investigate the prediction of
      unknown response factors from the molecular structure by using combustion
      enthalpies. In a first step, this enthalpy was well-predicted with either ab
      initio calculation or multiple linear regression based on the molecular formula.
      In a second step, good correlation was observed between these combustion
      enthalpies and experimental relative response factors, and so the response
      factors were predictable from only the molecular formula. With a database of 351
      compounds, about 60% of them exhibited a difference of less than 5% between the
      predicted and experimental relative response factors and about 80% exhibited a
      difference of less than 10%.

PMID- 20700912
TI  - Study of discontinuous atmospheric pressure interfaces for mass spectrometry
      instrumentation development.
AB  - The discontinuous atmospheric pressure interface (DAPI) has allowed the transfer
      of ions from atmospheric pressure ionization sources to an ion trap mass analyzer
      in hand-held mass spectrometers with miniature pumping systems at transfer
      efficiencies high enough for proper chemical analysis. The DAPI potentially would
      allow a significant enhancement to the mass analysis efficiency of laboratory
      scale mass spectrometers, which have pumping systems of much larger capacities. A
      laboratory-scale mass spectrometer with a DAPI-RIT (rectilinear ion trap)-DAPI
      configuration has been developed to explore this possibility. The gas dynamic
      effects on ion trapping and mass analysis have been studied at various
      conditions. A pulsed nanoelectrospray ionization source synchronized with the
      DAPI has been implemented to improve the sample usage efficiency as well as to
      adjust the number of ions to be trapped for MS analysis, so that space charge
      effects can be avoided. Single-scan spectra of peptides were recorded with an
      ionization time as short as 1 micros, corresponding to an analyte consumption of
      several attomoles. The simplicity of application of the DAPI for performing
      ion/molecule and ion/ion reactions has also been demonstrated with proton
      transfer and electron transfer dissociation reactions with peptides.

PMID- 20700913
TI  - Proceedings of the ESF-EMBO (European Science Foundation-European Molecular
      Biology Organization) Symposium. May 16-21, 2009. Saint Feliu de Guixols, Spain.

PMID- 20700914
TI  - High-throughput phospholipidic fingerprinting by online desorption of dried spots
      and quadrupole-linear ion trap mass spectrometry: evaluation of atherosclerosis
      biomarkers in mouse plasma.
AB  - This work presents a strategy for the evaluation of differences in plasma
      phospholipid content between atherosclerotic and healthy mice from micro volumes
      (2 microL) spotted on filter paper. Dried plasma spots (DPS) were directly
      desorbed into a triple quadrupole linear ion trap mass spectrometer using a
      homemade prototype, ensuring high-throughput analysis of dried spots without any
      sample pretreatment. Multiple positive and negative neutral loss and precursor
      ion scans were simultaneously acquired in a single loop, allowing oriented
      fingerprinting until 2700 potential species including phosphatidic acid (PA),
      phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylglycerol
      (PG), phosphatidylinositol (PI), phosphatidylserine (PS), and sphingomyelin (SM)
      classes. The phospholipidic variations between 15 healthy and 15 atherosclerotic
      mice were evaluated using t tests, matrix reduction and merging, and principal
      component analysis (PCA) as a chemometric statistical approach. The
      discriminating ions in PCA analysis were qualitatively identified in an
      information dependent acquisition (IDA) manner using enhanced resolution and
      enhanced product ion scans. PCA demonstrates a clear clustering between healthy
      and diseased mice. Regarding the most relevant variables identified, this
      procedure has confirmed the role of SM and PS classes in atherosclerosis and has
      established potential biomarkers shown to be significantly up- or down-regulated
      with the disease. The results presented in this work demonstrate the sample
      processing and analysis potential of the developed strategy to evaluate new
      biomarkers and the state of a disease.

PMID- 20700916
TI  - Proceedings of the Eleventh RCMI International Symposium on Health Disparities.
      Honolulu, Hawaii, USA. December 1-4, 2008.

PMID- 20700915
TI  - Predicting the clinical course of Hodgkin lymphoma.

PMID- 20700917
TI  - Proceedings of the Ninth Fatty Acids and Cell Signalling Meeting. July 13-16,
      2009. Oxford, United Kingdom.

PMID- 20700918
TI  - Proceedings and Abstracts of the Fifth International Conference on Thrombosis and
      Hemostasis Issues in Cancer. Stresa, Italy. April 23-25, 2010.

PMID- 20700923
TI  - APPROVED: Joint Commission eliminates special focus facility requirement.

PMID- 20700924
TI  - [Characteristics of lymphocyte enzymatic activity in children with Epstein-Barr
      infection].
AB  - Activity of NAD(P)-dependent dehydrogenases in peripheral blood lymphocytes from
      140 children aged 1-14 years with Epstein-Barr infection was studied. It was
      shown to depend on the disease duration and children's age. Disturbances of
      lymphocyte enzymatic activity persisted during the reconvalescence period.

PMID- 20700925
TI  - [Correlation between variations of self-stigmatization and quality of life in
      schizophrenic patients].
AB  - The work was aimed to analyse results of the study of self-stigmatization and
      quality of life in 345 schizophrenic inpatients. Five assertion clusters
      representing psychological constituents of 3 self-stigmatization variants were
      distinguished. Correlation between self-stigmatization variant and quality of
      life was established. The paper is intended for psychiatrists, psychologists, and
      health care providers.

PMID- 20700926
TI  - Grown-ups, quit wallowing.

PMID- 20700928
TI  - Worker immunization.

PMID- 20700929
TI  - Patient care. Revamped informed consent puts the patient at the center.

PMID- 20700930
TI  - Tecnology. E-IU programs expand thanks to new business partnerships.

PMID- 20700931
TI  - In the spotlight: The Equality Act.

PMID- 20700932
TI  - Under observation.

PMID- 20700933
TI  - A game of two halves.

PMID- 20700934
TI  - Sharing experience.

PMID- 20700935
TI  - Investigating the authorities.

PMID- 20700936
TI  - Outside the box: Depression.

PMID- 20700937
TI  - Welfare writes: Making benefits work harder for service users.

PMID- 20700938
TI  - Understanding personality disorders.

PMID- 20700939
TI  - The bigger picture: Cultural awareness training.

PMID- 20700940
TI  - Doctor's orders: Report on loneliness.

PMID- 20700941
TI  - Perspectives: Individual budgets could be used to help offset the cuts being made
      in adult education.

PMID- 20700942
TI  - Viewpoint: Continuing professional development.

PMID- 20700943
TI  - Viewpoint: Cuts on the horizon.

PMID- 20700944
TI  - Giving dementia a voice.

PMID- 20700946
TI  - Pediatric oncology: 11q negative neuroblastoma subgroups predict outcomes and may
      guide treatment.

PMID- 20700945
TI  - On the record: Looking at ordinary people's tales of living with their mental
      illness. Interview by Alita Howe.

PMID- 20700947
TI  - Screening: Four-kallikrein panel to reduce unnecessary prostate biopsy.

PMID- 20700948
TI  - Ethical considerations for normal control subjects in MRI research.
AB  - MRI is increasingly used as a research tool with the inclusion of "normal"
      control subjects, raising ethical issues when significant incidental
      abnormalities are found on research MRIs. We report two asymptomatic young men
      who had lesions discovered on MRIs performed for research in which they were
      acting as normal controls. We discuss the ethical considerations raised by these
      patients in imaging research, including appropriate subject selection, study
      design to include protocol mechanisms for incidental findings, informed consent
      and the need for expert clinical review of images.

PMID- 20700950
TI  - Proceedings from the 3rd International Symposium on Physiology and Pharmacology
      of Temperature Regulation, Matsue, Izumo, Japan, July 23-26, 2009.

PMID- 20700949
TI  - Nocardia cyriacigeorgica abscess of the conus medullaris in an immunocompetent
      host.
AB  - Conus medullaris abscesses are a distinct and rare subset of spinal
      intramedullary infections. We report a patient with a pyogenic abscess of the
      conus from which we cultured Nocardia cyriacigeorgica following operative
      evacuation. This is the first report identifying this species as a pathogen in
      conus abscess formation.

PMID- 20700951
TI  - Ferritin: structures, properties and applications. Special issue dedicated to
      Pauline M. Harrison.

PMID- 20700952
TI  - Flows and flaws in primary central nervous system lymphoma.

PMID- 20700953
TI  - An update on soy: It's just so-so.  The onetime health food champion is an
      excellent source of protein, but it hasn't lived up to its earlier billing.

PMID- 20700954
TI  - War on cancer won't be won in the produce aisle.  A large European study finds
      fruits and vegetables are only modestly protective against cancer, but it's a
      different story for heart disease.

PMID- 20700955
TI  - Colon cancer risk: a refresher course.

PMID- 20700956
TI  - New (still proposed) rules for sunscreen.  UVA testing and ranking may be the
      most important change.

PMID- 20700957
TI  - Depression research: an objective view of gloomy outlook.

PMID- 20700958
TI  - By the way, doctor.  I read that President Obama had a virtual colonoscopy.  Is
      this the colon cancer screening test that everybody should be getting instead of
      a regular colonoscopy?  I thought it was kind of experimental.

PMID- 20700960
TI  - [The A-to-Z of medical writing].

PMID- 20700961
TI  - [Cardiomyopathy in liver cirrhosis--an undiagnosed entity?].
AB  - Cirrhotic cardiomyopathy is a condition recently known in liver cirrhosis
      consisting of systolic dysfunction to stress factors, diastolic dysfunction and
      electrophysiological abnormalities in the absence of cardiac disease. The
      prevalence of cirrhotic cardiomyopathy remains unknown until now. It can be
      diagnosed by using a combination of electrocardiograph, 2-dimensional
      echocardiography, and various serum markers (brain natriuretic factor--BNP,
      proBNP, TnI). Pathogenic mechanisms underlying cirrhotic cardiomyopathy
      development include abnormal signaling betaadrenergic, cardiomyocites membrane
      fluidity changes, interstitial fibrosis, myocardial hypertrophy, altered
      transmembrane ion channels as intervention with negative inotropic effect of
      different substances whose concentration is increased in cirrhosis. Major
      stresses on the cardiovasculary system such as liver transplantations,
      infections, insertion of transjugular portosystemic stent-shunt (TIPSS) have been
      demonstrated to put in evidence the presence of cirrhotic cardiomyopathy. Heart
      failure is a significant cause of mortality after liver transplantation but the
      improvement of liver function determines cardiac abnormalities reversal. Current
      management recommendations include empirical, nonspecific and mainly supportive
      measures, no specific treatment can be recommended, and cardiac failure should be
      treated as in non-cirrhotic patients with sodium restriction, diuretics, and
      oxygen therapy when necessary. The exact prognosis remains unclear. The extent of
      cirrhotic cardiomyopathy generally correlates to the degree of liver
      insufficiency. Reversibility is possible (either pharmacological or after liver
      transplantation), but further studies are needed.

PMID- 20700962
TI  - [Viral hepatitis--trends].
AB  - Viral hepatitis is a serious health problem all over the world. The aim of the
      study is to present the actual achievements in the therapeutically field and the
      general knowledge concerning the subject. Are presented the etiological agents of
      the acute and chronic hepatitis with the focus on hepatitis B and C, which has
      become a priority of WHO, with an incidence of the diseases of 360 billion/year
      for hepatitis B and an sub estimated level for C hepatitis. The most used drugs
      are presented and the therapeutical combination meant to decrease biological and
      virusological markers (ALAT, viral load) and to ameliorate the histological
      aspects of the liver. In conclusion, acute and chronic viral hepatitis represents
      a challenge for epidemiologists who try to stop the spread of the disease, but
      also for the infectious diseases specialists and gastroenterologists.

PMID- 20700963
TI  - [Pharmacologic therapy in peripheral diabetic polyneuropathy].
AB  - Neuropathy is one of the many complications of diabetes mellitus, along with
      micro- and macroangiopathy. Chronic sensorimotor distal symmetric polyneuropathy
      is the most common form between neuropathies; more than 30% of the diabetic
      patients are affected by this complication. Treatment is based on three
      cornerstones: (1) multifactorial intervention aimed at normoglycemia; (2) drugs
      that target pathogenic mechanisms and (3) symptomatic treatment. Among pathogenic
      treatments, alpha-lipoic acid and benfotiamine are available in several
      countries. Neuropathic pain, which affects 8-26% of diabetic patients, exerts a
      substantial impact on the quality of life. Among the centrally acting analgesic
      drugs, tricyclic antidepressants, carbamazepine, gabapentin and opioids have been
      mainly used to treat neuropathic pain. More recently, significant pain relief has
      been reported using agents such as duloxetine, a dual selective serotonin
      noradrenaline reuptake inhibitor, and pregabalin, an anticonvulsant, a specific
      modulator of the alpha2delta subunit of the voltage-dependent calcium channels.
      Until now, at least 50 new molecular entities have reached clinical stage of
      development. Strategies that may show promise over existing treatments include
      topical therapies, analgesic combinations and, in future, gene-related therapies.

PMID- 20700964
TI  - [Noncardiac chest pain and gastroesophageal reflux disease].
AB  - Gastroesophageal reflux disease (GERD) may manifest typically with heartburn and
      regurgitation or may have atypical manifestations as laryngitis, asthma, chronic
      cough or noncardiac chest pain (NCCP). While typical GERD is easy to be
      recognized, the atypical extraesophageal symptoms of the disease make the
      diagnosis difficult because most patients do not have heartburn or regurgitation.
      Most common atypical manifestations include ear, nose and throat (ENT), pulmonary
      or cardiac symptoms. GERD should be included in the differential diagnosis of
      patients with atypical symptoms, especially when alternative diagnoses are
      excluded. NCCP is defined as recurring angina-like substernal chest pain of
      noncardiac origin. We present the most recent epidemiologic data,
      pathophysiology, diagnosis and treatment of NCCP. The major causes of NCCP are
      GERD and esophageal dysmotility. By far, GERD has been demonstrated to be the
      most frequent source of NCCP. After a complete cardiac evaluation, the patient
      with NCCP will be referred to a gastroenterologist. All recent studies suggest
      the use of PPI test as the first diagnostic tool in patients with NCCP. The
      invasive diagnostic tests (especially, the 24-hour pH monitoring and esophageal
      manometry) are used only in those cases who do not respond to PPI therapy.
      Patients with GERD-related NCCP require long-term treatment with a PPI.

PMID- 20700965
TI  - [Some cardiovascular effects of alcohol. Prospective study on 200 patients
      between 2006-2008].
AB  - Several studies have confirmed that drinking a moderate amount of alcohol
      (ethanol) decreases the risk of heart disease, heart attack, and stroke. There
      are several mechanisms of health benefits of alcohol, which include
      antiinflammatory, antioxidant and anti-blood clotting effects. The aim of the
      study is to underline the effects of alcohol consumption over cholesterol blood
      levels. MATERIAL AND METHODS: The study was conducted on 200 individuals from
      urban and rural areas of Iasi county (100 being alcohol consumers), during the
      2006-2008. RESULTS: The cholesterol blood levels are greater than the normal
      accepted values, both in men and women (urban and rural), drinkers or
      nondrinkers. CONCLUSION: The cholesterol levels are higher in drinkers, women and
      rural population included in our study. We did not do a quantification of other
      factors which may increase the cholesterol blood levels, such as diet, body mass
      index and physical activities.

PMID- 20700966
TI  - [Endo-histological correlation in chronic Helicobacter pylori gastritis].
AB  - In this study, we analysed the correlations between endoscopic aspects and
      histopathological changes at the patients with dispeptic simptoms and anti
      Helicobacter pylori antibodies, investigated with upper endoscopy. MATERIAL AND
      METHODS: Our study comprised of 418 patients from Bacau Hospital, in period
      October 2005 - October 2008. Histopathological diagnosis was correlated with
      endoscopic aspects. RESULTS: Average age was 55 years, with predominance of woman
      and rural people, without statistical significance. Histopathological diagnosis
      of nonatrophic gastritis was found at 211 (50%) patients, atrophic gastritis at
      192 (46%) patients, intestinal metaplasia at 108 (26%), low grad intraepithelial
      neoplasia at 70 (17%), high grad intraepithelial neoplasia, at 4 (1%) patients,
      neoplasia at 28 (7%). The most severe diagnostic was atrophic gastritis with
      intraepithelial neoplasia. Our analysis has found nonatrophic gastritis in 211
      patients (50%), atrophic gastritis in 192 (46%), intestinal metaplasia in 108
      (26%), low grade intraepithelial neoplasia in 70 (17%), high grade
      intraepithelial neoplasia in 4 (1%), superficial gastric carcinoma in 27 (7%) and
      one MALT lymphoma. CONCLUSION: There was no correlation between the endoscopical
      aspects and the histological diagnosis. All histological changes were strongly
      related to Helicobacter pylori infection. Prospective studies are needed to
      evaluate whether the eradication of Helicobacter pylori will indeed reduce the
      risk of gastric cancer.

PMID- 20700967
TI  - [Intentional poisoning with ACE inhibitors. Emergeny Hospital Iasi].
AB  - Regarding angiotensin-converting enzyme inhibitors (ACEI) poisoning, only few
      data are available in the last decade literature. In the previous couple of years
      especially isolated case reports were published. MATERIAL AND METHOD: We analyzed
      retrospectively all the patients with acute ACEI poisoning admitted in Iasi
      Internal Medicine and Toxicology Clinic between 2004 and 2009. RESULTS: 17 cases
      of poisoning were recorded (enalapril-9 cases, captopril-3 cases, perindopril-3
      cases, lisinopril-2 cases). All the poisonings were intentional. A favorable
      outcome was consistently observed, and were recorded no sequelae or death in this
      study. The main complain was hypotension, required fluid administration, only one
      case with 500 mg enalaprilum and severe hypotension required injection of
      vasopressive amines. No abnormal renal function and no angioedema were noted.

PMID- 20700968
TI  - [Helicobacter pylori infection and symptoms of gastroesophageal reflux disease].
AB  - The effect of Helicobacter pylori (H. pylori) on gastroesophageal reflux disease
      (GERD) is controversial. The aim of this study was to assess the relationship
      between H. pylori infection and symptoms of GERD. MATERIAL AND METHOD: 112
      patients (41 men, 71 women; mean 51 +/- 9.54 yeas, range 21-71 yeas) with
      symptomatic GERD were studied. The serologic evidence of H. pylori infection (IgG
      antibodies) was determined by means of ELISA ( enzyme-liked immunosorbent assay)
      in all patients. RESULTS: There were 59 (53.2%) patients infected with H. pylori.
      Statistical analysis did not reveal any significant different symptom scores
      between patients with and those without H. pylori infection. CONCLUSIONS: H.
      pylori infection plays no role on the development of GERD symptoms.

PMID- 20700969
TI  - [Effect of cpap therapy on sleep quality in patients with OSAS].
AB  - For an adequate analysis of sleep quality was assessed a new composed index wich
      objectively approached variate polisomnographic parameters. We used this new
      concept--sleep disturbances index-SDI in patients with obstructive sleep apnea
      (OSAS), before and after the beginning of CPAP therapy. MATERIAL AND METHOD: 41
      patients were evaluated and for each one we calculated SDI score. All patients
      were split in two groups according with apnea-hipopnea index (AHI), and we
      correlated SDI with AHI as marker of severity of the disease and with Epworth
      Sleepiness Scale's scores, as an subjective evaluation. After 1 month of CPAP
      therapy, SDI was reevaluated. RESULTS: SDI is correlating with the severity of
      the disease: for group 1, with 5 < AHI < 15, SDI= 2.24 +/- 0.88, r = 0.53, p <
      0.01 and for group 2, with AHI >15, SDI = 3.23 +/- 0.69, p < 0.01, r = 0.46.
      There was no significant correlation between SDI and ESS scores (r = 0.23, p <
      0.01). SDI lowers significant during CPAP therapy: SDI= 1.48 +/- 0.60, respectiv
      SDI = 1.90 +/- 1.23. CONCLUSION: The severity of OSAS is correlated with
      increased SDI, but can be seen interindividual variability. The effect of CPAP
      therapy is reflecting also in sleep quality.

PMID- 20700970
TI  - [Treatment of acute peritonitis. Results in County Hospital Suceava with 317
      cases ].
AB  - The aim of this study was to identify prognostic factors for morbidity, mortality
      and long term outcome and to analyze the different management modalities for
      acute diffuse peritonitis. MATERIAL AND METHOD: A clinical retrospective study
      was carried out on a series of 317 cases with acute peritonitis; admitted in the
      General Surgery Department, Hospital of Suceava, between 2006-2009. RESULTS:
      There were 212 men (67%) and 105 women (33%) aged between 1 and 89 years.
      Preoperative concomitant disease was present in 31% of patients: cardiac disease
      was most common. The most common etiology was acute appendicitis in children 74
      of cases (27.6%). Overall, 44 patients died during hospitalization. The cause of
      death was sepsis and multiple organ failure in 30 patients; malignancy in 8
      patients and cardiac failure in 6 patients. Source control at the initial
      operation was possible in 282 of the patients (89%), of those 28 patients (9%)
      needed re-intervention. In 32 patients (10%), source control was not possible at
      the initial operation. CONCLUSION: This study emphasis the importance of prompt
      surgical treatment and shows the impact of adapting antibiotic treatment.

PMID- 20700971
TI  - [Clinical and epidemiological aspects of patients with acute viral hepatitis in
      Bacau county, from 1996 TO 2005].
AB  - The purpose of the study is to emphasize the clinical and epidemiological
      peculiarities of acute viral hepatitis in the last decade. MATERIAL AND METHOD:
      We studied retrospectively the files of 2014 patients, hospitalized with the
      diagnosis of acute viral hepatitis in the Bacau County Hospital, from 1996 to
      2005. RESULTS: We saw that the only type the incidence of which lowered in time
      was the B-type hepatitis. The A acute hepatitis witnessed two epidemic peaks. The
      clinical cases of the male young patients prevailed. In 91.6% of cases, the
      infection source could not be established. The average incubation period was 21
      days for viral hepatitis A, 65 for B and 80 for C. Hospitalized anicteric forms
      represented 2.8% of total. Extended forms were recorded with 3.6% patients (50.9%
      of them with B virus) and severe forms with 10.3% (among these, 66.7% with B
      virus). A fulminate evolution was noticed with 0.65% of cases. The global
      mortality was 0.4% and 0.95% for B type. CONCLUSIONS: We noticed several
      peculiarities and changes regarding the clinical and epidemiological aspects of
      acute viral hepatitis in the last

PMID- 20700972
TI  - [Viral patology and oral manifestation].
AB  - Although the medical and biological importance of ringworm infections was
      acknowledged a long time ago, the putting-up-to-date of some clinical notions is
      justified for at least three reasons: the improvement and accessibility of
      molecular biology techniques, the consideration of the major pathogenic role of
      these viruses in circumstances of immune depression, the possibility to control
      these infections by means of specific chemotherapy. MATERIAL AND METHOD: A
      prospective study was carried out in the interval 1.01.2006 - 31.12. 2008, of all
      cases of ringworm infections with oral eclat, hospitalised in Infectious Diseases
      Hospital Iasi. The diagnosis was established according to the clinical
      manifestations, the hematological modifications and, if the case, serological
      examination. RESULTS: The study included 291 cases. The infection with EVB
      (infectious mononucleosis) was diagnosed within the age interval 8 months-60
      years (median-10 years). The oral manifestations were mainly located at the level
      of the palatine and velopalatine vault. Chickenpox was diagnosed within the age
      interval 7 days-52 years (median-8 years). The chickenpox enantem was observed in
      90.42% of the cases, being represented by varix wounds, or "hemorrhagic spots",
      mostly located at the level of the fibrous mucose membrane of the palatine vault-
      40.2%. CONCLUSIONS: The knowledge of the oral manifestations in ringworm
      infections with highly contagious potential and a high risk of severe
      complications represents a fundamental method in early diagnosis as well as an
      important step in establishing the prophylaxy measures meant to prevent these
      pathogens from being transmitted to the dentist office.

PMID- 20700973
TI  - [Practical aspects of sepsis from oral bacterial infections].
AB  - Infections of the oral cavity are an important morbidity problem due to their
      frequency, their pluribacterial ethiology as well as their potential severe
      evolution, especially with the immunodepressive. The odontogenic infections are
      considered to be the cause of 40% of the deep throat infections. The infections
      of the submentonier space occur through direct extension from the mandibular
      incisors, those of the sublingual space start from the anterior mandibular teeth
      and those of the retrofaringian space start from the mandibular molar teeth.
      MATERIAL AND METHOD: The present study included 24 pacients diagnosed with oral
      sepsis in Iasi Infectious Diseases Clinic. We analysed the ethiology and the
      clinical response to the administered antibiotherapy. RESULTS: In several
      immunodepressed patients (with diabetus melitus, neutropenia, liver disfunction,
      carcinomas, tuberculosis) was noted sistemic evolution of odontogenic infection
      and they mainly came from the Surgery Clinics, where surgery was performed for
      the drainage of collections. Etiology was confirmed in 8 cases reflecting normal
      oropharyngeal flora. These infections were treated with antibiotics in
      synergistic combinations (betalactamines, quinolones, Cloramfenicol) with good
      results in 19 cases. CONCLUSION: Infections of the oral cavity are an important
      morbidity problem due to their frequency, their pluribacterial origin as well as
      their potential severe evolution, especially in immunodepressed patients.

PMID- 20700974
TI  - Socioeconomic implications of underdiagnosing teenagers' depression.
AB  - The aim of our research was to demonstrate once again that teenagers' depression
      still remains way too much underdiagnosed, the last one having important
      socioeconomic implications. Thus it is absolutely necessary to implement
      depression screening in psychiatric clinics. MATERIAL AND METHOD: The study was
      carried out in 2 stages, I; a group of 1126 in-patients from "Sf. Maria"
      Hospital, and II the analysis of the socioeconomic implications of teenagers'
      depression. RESULTS: Only 19, 11% of the depressive patients had a previous
      depression diagnosis, the rest of 80, 89% were new cases, recently diagnosed; the
      depressive teenagers are more exposed to drugs and alcohol abuse, to antisocial
      behavior, and to poorer results in school. CONCLUSION: Screening depression
      implementation would reduce very much the risk of teenagers' depression
      underdiagnosing.

PMID- 20700975
TI  - [Effect of preoperative administration of prostaglandin E1 on cerebral blood flow
      in newborns with ductal-dependent congenital cardiac malformations].
AB  - Although the absolute number of congenital structural heart disease has not
      changed over the years, more and more infants undergo surgical interventions in
      the neonatal period, increasing the number of children and adults with post
      surgical status of cardiac disorders. Prostaglandin E1 (PGE1) is the first line
      drug to maintain or reopen the ductus arteriosus, until surgical intervention can
      be made. Cerebral blood flow (CBF) is regulated by multiple factors, like pO2,
      pCO2, pH, cardiac output and systemic blood pressure. The aim of the study was to
      determine how CBF changes after PGE1 administration in these newborns. MATERIALS
      AND METHODS: We studied the pO2, pCO2, mean systemic blood pressure, and cerebral
      blood flow velocities by colored and pulsed Doppler ultrasonography in 36
      newborns with ductal dependent cardiac malformation before and after
      prostaglandin E1 administration, and correlated them to normal values for the
      age. RESULTS: We found that cerebral blood flow velocities followed the
      variations of blood pressure in restricted pulmonary circulation; improvement of
      oxygenation went parallel with decrease of cerebral diastolic velocities, and in
      aortic coarctation cerebral velocities decreased after introduction of PGE1.
      CONCLUSIONS: PGE1 administration improved cerebral blood flow velocities in all
      forms of cardiac malformations, due to reorganization of cardiac output and
      changes in oxemia. Key

PMID- 20700976
TI  - [Height and weight growth delay and protein-energy malnutrition in children with
      chronic dialysis].
AB  - Growth retardation is an important problem in children with chronic renal
      disease, and malnutrition is a determinative factor. AIM: The study intends to
      assess the relationship between protein-energy malnutrition and stature-weight
      retardation in children enrolled in chronic dialysis program. MATERIAL AND
      METHOD: The study group was composed of 16 children (5 boys and 11 girls--sex
      ratio of 2.2) hospitalized in the IVth Nephrology Clinic at Clinical Emergency
      Hospital "St. Maria" Iasi, 13 rural and 3 urban, aged between 9 and 17 years,
      with chronic dialysis program. This was a follow-up study during a period of 4
      years (2006-2009), resulting in correlations between anthropometric paremeters,
      biochemical, BIA and DEXA data. RESULTS: The stature-weight deficiency of the 16
      patients was as follows: after an average period of 61.7 months of HD and 32.7
      months of PD, in children older than 12 years (mean age 15.27 years), 7 of 10 had
      stature-weight deficits higher than (-3DS) or (-4DS). The group with less than (
      2DS) stature-weight deficits showed the same mean age of 15.2 years, the protein
      energy-malnutrition was present in 2 cases (33%) and was attributed to a dialysis
      period shorter than 13.8 months. CONCLUSIONS: The late diagnosis of the disease
      (at an average age of 13 years), the long period of chronic dialysis program
      (over 39.5 months on average) and the early debut of malnutrition are favoring or
      worsening factors of stature-weight retardation. After correlating ESG with
      biochemical, BIA and DEXA data, in our group were identified 4 cases of moderate
      malnutrition and 9 cases of severe malnutrition.

PMID- 20700977
TI  - [Characteristic features of urinary tract infection in malnourished children].
AB  - The aim of this study is to prove a relationship between urinary tract infection
      and malnutrition in children 0-3 years old, hospitalized in the IVI Pediatric
      Clinic, Hospital St. Mary Iasi, between January 2000 and December 2004. MATERIAL
      AND METHODS: We have made a retrospective study for 298 infant and young children
      with urinary tract infection, 237 eutrophic and 61 malnourished. We studied
      comparatively the both groups with urinary tract infection (UTI), and we applied
      statistic methods for results. RESULTS: The statistic methods prove that relative
      risk for UTI increases in malnutrition, predictive positive value is 72.5%. The
      clinical manifestation is similar in malnourished and eutrophic, but many co
      morbidities were associated with dystrophic status. Malformation of urinary tract
      was associate two times more in malnourished child. The etiology of infection was
      dominated by Escherichia coli, Proteus and Klebsiella pneumoniae. In malnourished
      children 5% of UTI was determinate by opportunist etiological agents like:
      Enterobacter, Enterococcus, Acinetobacter. More frequently, bacterium develops
      resistance of antibiotics like amino-penicilina, Trimethoprim and Cephalosporin.
      CONCLUSION: Accurate and fast diagnosis and treatment of UTI in infant and child
      with malnutrition is the best way for nutritional rehabilitation and prevention
      of serious consequence.

PMID- 20700978
TI  - [Diamond-Blackfan anemia. Case report].
AB  - Diamond-blakfan anemia (DBA) is a rare condition in pediatric pathology, with
      more than 500 cases described in literature. It is a congenital
      eritroblastopenia, with AD/AR/ X-linkage inheritance, 90% were diagnosed by one
      year of age. Physical appearances were abnormal only in 29%. The current
      recommendations are corticosteroids, with suportive treatment and bone marrow
      transplantation. In general, DBA remains a single cytopenia. Long term prognosis
      remains uncertain, DBA is a preleukemia condition. We present two cases that we
      took care of in our clinics.

PMID- 20700979
TI  - [Children's Langerhans cell histiocytosis, diagnostic problems].
AB  - Langerhans cell histiocytosis is a group of idiopathic disorders characterized by
      the proliferation of cells of the mononuclear phagocyte system and the dendritic
      cell system. From the clinical point of view there are 3 forms of histiocytosis
      encountered in child pathology: acute, disseminated called Abt-Letterer-Siwe (it
      usually affects children under 2 years of age), eosinophilic granuloma and the
      intermediate clinical form called Hand-Schuller-Christian disease. We present the
      case of a premature born child that had, even from the day she was born, a rash
      disseminated on the entire surface of the body associated with enlarged lymph
      nodes, hepatosplenomegaly and thrombocytopenia. The diagnosis of Langerhans cell
      Histiocytosis is difficult to establish and this case is an example that confirms
      it. Therefore, we present the difficulties in diagnosing this case and its
      particular evolution.

PMID- 20700980
TI  - [Breast cancer in the male].
AB  - The aim of this study is to point out the late diagnosis and initiation of
      treatment in male with breast cancer. At the same time, to show the importance of
      the correlation between different markers in assessing the prognostic, as well as
      the treatment for the patient. MATERIAL AND METHODS: Retrospective study on a
      group of 15 males with breast cancer, out of 1043 patients with the disease, in a
      period of 10 years. Eight patients were stage III of disease, 2 were stage II,
      one was stage I, and in other 3 cases the evaluation of the tumor and of the
      axillary lymph nodes was performed only by echography, considered stage II.
      RESULTS: All patients underwent radically modified Madden mastectomy; 4 patients
      needed a partial resection of the great pectoralis muscle. Adjuvant chemotherapy
      was performed in 9 patients, and neoadjuvant chemotherapy in 2 cases. Three
      patients refused the chemotherapy, and one patient chose an alternative
      paramedical treatment. The treatment with Tamoxifen was done in 11 patients with
      high values of Progesterone and Estrogen Receptors (PR, ER). At the date of our
      study, 8 patients were alive, without clinical signs of disease (free of
      disease), while in 3 patients, alive, clinical signs of disease were detected
      (recurrence). Survival rate couldn't be evaluated in 4 patients. CONCLUSIONS:
      Breast cancer in male is usually discovered in locally advanced stages, although
      most of the patients are regularly screened for chronic hepatitis. Use of
      biological markers allows a more accurate evaluation of the aggressiveness of the
      tumor, as well as a more specific treatment for each patient. Modified radical
      mastectomy type Madden remains the preferred surgical approach. Surgical approach
      should be considered even in locally advanced cases, as well as in elder
      patients.

PMID- 20700981
TI  - [Surgery in advanced cervical cancer].
AB  - The aim of this study was to highlight the importance of surgical treatment in
      advanced cervical cancer (IIB-IIIB). MATERIAL AND METHOD: Data from 179 patients
      with cervical cancer, admitted in the Clinic of Emergency Surgery, "Sf. Ioan"
      Hospital, Iasi, between January, 1st, 2003 and December, 31st, 2009, were
      collected. RESULTS: A number of 11 cases (6.1%) cases were without any clinical
      response, so that they benefit by radical radiotherapy; a radical surgical
      intervention was performed in the other 168 cases (93.7%), in 4-6 weeks after
      chemotherapy. No intraoperative complications were evidenced, but after surgical
      intervention we recorded: urinary troubles--10 (6.5%); lymphedema--3 (1.9%);
      posttoperative intestinal occlusions--2 (1.3%); extended dynamic ileus--2 (1.3%);
      phlebitis--2 (1.3%).

PMID- 20700982
TI  - [Renal colic in pregnancy].
AB  - Renal colic in pregnant women is a serious condition, mainly when is associated
      with fever. MATERIAL AND METHOD: Our retro-prospective study analyzes 111 cases
      managed conservatively or with endourological procedures for renal colic-
      insertion of JJ stents and percutaneous nephrostomy. RESULTS: Clinical evolution
      determined the insertion of JJ stents in 60 cases and the failure of this
      procedure imposed percutaneous nephrostomy in 5 cases. In 56 cases urinary tract
      infection was associated and in 2 cases, despite all efforts, the patients
      deceased due to sever sepsis. CONCLUSIONS: The immediate drainage of the upper
      urinary tract for renal colic in pregnancy is the recommended treatment,
      especially when the pain is associated with fever. JJ stens were well tolerated,
      even when they were replaced after 3 months. Pregnant women with a history of UTI
      or stone disease should be carefully followed-up.

PMID- 20700983
TI  - [Endometrial hyperplasia, diagnosis. Clinical, paraclinical exam and management].
AB  - Factors associated with unopposed estrogenic stimulation such as obesity,
      exogenous hormone use endometrial hyperplasia are related to the development of
      the most common form of endometrial carcinoma, that is, the endometroid subtype.
      MATERIAL AND METHODS: We selected a group of patients diagnosed with endometrial
      hyperplasia by endometrial biopsy and histopathological examination. The main
      complaint in all cases was abnormal uterine bleeding. All patients had
      gynecological examination, vaginal ultrasound, hysteroscopy endometrial biopsy or
      D&C. 32 patients had also immunohistochemical staining for Ki67, EGF, ER, PGR.
      RESULTS: Cases with ages between 24-67 years were classified as: 100 simple
      hyperplasia, 10 complex hyperplasia, 43 atypical simple hyperplasia, 7 atypical
      complex hyperplasia. PR were 40-60% at all forms of hyperplasia, E2R were 30-40%
      in simple hyperplasia without atypia and 50-70% in complex hyperplasia without
      atypia. Correlation between immunohistochemical expression of E2R, PGR, Ki-67,
      EGF and body mass revealed an high immunohistochemical expression of E2R and Ki
      67 in patients with hyperplasia without atypia and a low expression and high
      reactivity of EGF in cases with high body mass. CONCLUSIONS: Vaginal ultrasound
      and hysteroscopy are efficacious completion for histopathological diagnosis. We
      recommend an age/risk appropriate screening to detect risk factors and early
      disease in the asymptomatic patients.

PMID- 20700984
TI  - [Cardiac response as stress marker in surgery].
AB  - Surgical area--as a precursor of negative emotions, is the threshold between the
      two areas of anxiety and anxiety among the general and specific stimuli. By
      dominant color, noise, odors and environmental factors in complex anxiety these
      elements define the specific treatment of dental medicine better. The emotional
      stress on the patient child which undergoes a surgical dento-alveolar therapy is
      negative and consists of the combination of three important elements, in close
      relationship: score of dental anxiety, the anticipation and experience of pain
      and phobic stimuli which is implicitly true precursor of pain. MATERIAL AND
      METHOD: Our study was performed on 448 patients. Different methods of
      preanesthesia were made per oral, intravenous, intramuscular, according with DAS
      score: Midazolam, Diazepam + Algocalmin, Xanax. RESULTS: 58% of our patients
      declare after surgery that their satisfaction score is 100% positive after one of
      our method of preanesthesia. CONCLUSIONS: The purpose of premedication should be
      unconditionally determined by the effect of the analgesic and anxiolytic drugs to
      improve cardiac response and avoid medical emergency. Doses administered must be
      correlated with the anxiety score DAS, road use and the probable duration of
      surgery.

PMID- 20700985
TI  - Diagnostic value of a negative single color duplex ultrasound in deep vein
      thrombosis suspicion during pregnancy.
AB  - OBJECTIVE: to determine whether a negative single complete ultrasound (US) of the
      lower limbs veins is a safe and accurate diagnostic method to rule out deep
      venous thrombosis (DVT) in pregnancy. MATERIAL AND METHODS: We performed a
      prospective study on 87 consecutive pregnant women with clinical suspicion of DVT
      in "Dr. D. Popescu" Maternity, Timisoara, between January 2007 and December 2009.
      All cases were investigated by color duplex ultrasound. Those who were negative
      but with high clinical probability of DVT underwent MR venography, the rest with
      negative US findings did not received anticoagulant therapy and US was repeated
      after seven days. All were instructed about the signs and symptoms of DVT and
      asked to return at six weeks postpartum when they were questioned if presented
      any. RESULTS: from the 87 women 30 (34.48%) were found positive and two (2.29%)
      had a high clinical suspicion of DVT. 55 (63.21%) with negative findings repeated
      the US exam after 7 days which remained negative. Only 43 (78.18%) returned for
      the 6 weeks postpartum visit and none of them experienced any thromboembolic
      event during follow-up. CONCLUSIONS: A single complete color duplex
      ultrasonography of lower limbs veins appears to be a safe method to rule out the
      diagnosis of deep venous thrombosis in pregnant women and if negative is safe to
      withhold heparin therapy.

PMID- 20700986
TI  - [Contribution to improve the effectiveness of preventive interventions in order
      to reduce the risk of endomyoparametritis and surgical wound infections].
AB  - There are few new methods conferred an efficient prevention in order to reduce
      the incidence of endometritis after cesarean section. The study aim was to
      compare two techniques using in post partum post-cesarean endometritis
      prevention: local (vaginal) intra-partum application of 0.25% Clorhexidine
      solution during elective cesarean deliveries vs intraoperative cesarean section
      antibioprevention with 2g second generation cephalosporin administered by
      intravenous injection after clamping the umbilical cord.

PMID- 20700987
TI  - [Unique monoblock lung right-left, unique pleural cavity].
AB  - A 34-year-old female with WPW syndrome has been under surgical treatment in our
      clinic with left basal chronic pleural empyema. During the surgical intervention
      multiple anatomical anomalies were detected, like unique pleural cavity,
      monoblock lung left-right, hypoplasic left lung, no scissures on the left side,
      no left pulmonary arteria with an aberrant arteria for the left lung derived from
      the right pulmonary arteria, the same for the bronchis. The pleural-pulmonary
      shelling proceeded without incidents and it has been finalized with the drainage
      of the whole pleural cavity.

PMID- 20700988
TI  - [Agnogenic myeloid metaplasia in pregnancy. Case report].
AB  - Idiopathic myelofibrosis is a rare myeloproliferative disorder characterized by
      excessive accumulation of connective tissue in the bone marrow in association
      with anemia, splenomegaly and extramedullary hematopoiesis. A rare case of
      pregnancy in a patient with agnogenic myeloid metaplasia who carried a term
      pregnancy is described. In spite of the increased perinatal risks, a favorable
      outcome was possible with close antepartum surveillance. CONCLUSION: Idiopathic
      myelofibrosis was once thought to be a contraindication to pregnancy. With
      careful management, successful pregnancies can be achieved.

PMID- 20700989
TI  - Clinical applications of molecular biomarkers in prostate cancer detection.
AB  - Prostate cancer is a heterogeneous disease with regard to molecular alterations
      and clinical course. Early diagnosis of prostate cancer can increase the curative
      success rate for this disease. Because of the recent developments in the field of
      molecular biology, an increased interest occurred for molecular biomarkers, as
      tools for early prostate cancer detection, monitoring disease progression,
      predicting disease recurrence and therapeutic treatment efficacy. Many molecular
      biomarkers have been discovered in human serum, urine, seminal fluid and
      histological specimens.

PMID- 20700990
TI  - [A comparaison between the total PSA, the Gleason score and the bone scintiscan
      results for different age groups].
AB  - The aim of the study is to compare de results of the bone scintigraphy of
      prostate cancer patients in different age groups with their total PSA (PSAt) and
      with their histopathological test results. MATERIALS AND METODS: Of the 180
      patients with prostate cancer who were analyzed by Scintiscan in the last five
      years in our laboratory, 86 have a known PSAt value, and of these, 55 have a
      known Gleason Score. The 180 patients were divided into three age groups: (1) <
      or equal 60 years; (2) 60-70 years and (3) >70 years. The 86 patients with a
      known PSAt were also divided into five groups according to their PSAt value and
      the 55 patients with a known Gleason Score were divided in three groups. The
      scintigraphy results included all the patients in 3 groups, according to the
      presence, the absence or the likelihood of having bone metastasis. The 33
      patients with proven bone metastasis were divided, according to their numbers,
      into the four Soloway groups. RESULTS: Among the patients with PSAt >20 ng/mL,
      considered high risk for bone metastases, according to the Recomandations of
      CCAF, 21 (32.81%) of the 64 patients do not show the presence of bone metastases.
      For PSAt >50 ng/mL, all 5 patients <60 years of age have metastases, while only
      15 (62.5%) of the 24 patients over 70 years old have metastases and 1 (4%) has
      low likelihood. 6 (21.42%) of the 28 patients with PSAt > sau egal 100 ng/mL do
      not have metastases. 10 (43.4 %) of the 23 patients with a Gleason Score <7,
      considered low risk, do have metastases (6 patients--26%) or low probability of
      metastases (4 patients--17.4%). CONCLUSIONS: Our study confirms that the
      probability of bone metastasis for a high PSAt value is reversely proportional to
      age. In our study there is no direct correlation between Gleason Score and the
      bone scan results.

PMID- 20700991
TI  - [New polymer-drug systems based on natural and synthetic polymers].
AB  - The great versatility of polymers makes them very useful in the biomedical and
      pharmaceutical fields. The combination of natural and synthetic polymers leads to
      new materials with tailored functional properties. The aim of this work consists
      in the preparation of new drug delivery system based on chitosan (natural
      polymer) and polybetaines (synthetic polymers), by a simple process, well known
      in the literature as complex coacervation methods. Also, the adsorption and
      release studies of two antibiotics as well as the preservation of their
      bactericidal capacities were performed.

PMID- 20700992
TI  - [Anatomical variations of landmarks in endoscopic surgery of the paranasal
      sinuses revealed by MRI imaging].
AB  - Continue development of endoscopic techniques of rinosinusal approach involves
      knowledge about the anatomy of this region, with a three-dimensional orientation
      before surgery, a therapeutic plan well thought, anticipating the gesture
      controller, taking into account the particularities of each case. Endoscopic
      surgical anatomic variants parts at this level can be well identified by imaging
      methods (CT, MRI). CT study of patients who are candidates for surgery Fess is on
      top, as the technique of choice. MRI is the imaging method to supply the CT data,
      providing a study carried out the normal anatomy and standard deviation of the
      numerous variants, single or in combination. This paper aims a randomized
      retrospective study of 120 MRI of the head and face region, to investigate and
      highlight the anatomical variations of structures at this level of impact and
      those with sinusitis etiopatologia, as well as those with operative risk
      (bleeding complications, ocular, vital risk) to determine the prevalence in the
      general population and have to compare the data with the literature. Using all
      sections (axial, sagittal and coronal) with the aid of different sequences (T1,
      T2, Flair and diffusion) allowed study of three-dimensional images of whole rhino
      sinus-related pathology. Anatomic variations of surgical landmarks have
      investigated a wide range of expression, which are unique or associated with a
      complex architecture, with sufficient accuracy and visible on MRI. Their
      prevalence in the group studied was generally consistent with the literature
      studied.

PMID- 20700993
TI  - [The effects of some nonpolar aminoacids--valine, leucine--administration on the
      arterial wall already exposed to a hypercholesterolemic diet].
AB  - Hypercholesterolemia plays an important role in atherosclerosis. The dietary
      supplementation of proteins or specific aminoacids seems to enhance the immune
      status in animals and humans with a complex pathological status, decreasing
      morbidity and mortality. AIM: In the present study we intended to analyse the
      effects of some nonpolar aminoacids--valine and leucine on cholesterol blood
      levels in a high-fat-diet in rats. In the same time we evaluated the vascular
      walls impact produced by the hypercholesterolemic diet. MATERIAL AND METHODS: Our
      experiment was realised on 32 male Wistar rats, which were fed with cholesterol,
      valine and leucine for 8 weeks. At the end of experiment we analysed serum levels
      of cholesterol and also histopathological features of hypercholesterolemia on the
      arterial wall. CONCLUSION: The results of our study indicate that valine and
      leucine decrease the serum cholesterol and therefore the hypercholesterolemic
      induced prooxidant status of the body being useful in reducing atherosclerosis.

PMID- 20700994
TI  - [Research on immune system response, skin and hepatic reactivity in laboratory
      animals after retro-auricular topical administration of two reactive textile
      dyes].
AB  - AIM: To evaluate immune system response, skin and hepatic reactivity in Swiss
      mice after retro auricular local administration of two textile dyes. MATERIAL AND
      METHODS: On 3 groups of white Swiss mice: group I (Cibacron Yellow F-4G), group
      II (Cibacron Orange P-2R) and control group (DMSO dimethylsulfoxide), substances
      were applied on left retro auricular ear, in dose of 25 microL solution 10% in
      DMSO (the dyes were not soluble in water), once a day, for 7 days. After
      euthanasia, blood samples were taken to assay differential cell count, peripheral
      neutrophils activity (NBT test), serum opsonic capacity, peritoneal macrophages
      activity (phagocytic and bactericidal capacity), and activity of spleenic T
      lymphocytes with rossetting capacity, and spleen cells forming Jerne plaques.
      There were taken skin from local application of dyes, retro auricular and later
      cervical nodes from left side and hepatic samples. RESULTS: Retro auricular and
      later cervical nodes mass increases after administration of textile dyes,
      compared to control group. Basophiles percentages were increased after
      administration of two dyes (stronger after yellow dye). Peripheral neutrophils
      activity was increased after administration of two dyes, especially after orange
      dye. Administration of the two dyes decreased serum opsonic capacity and
      peritoneal macrophages activity, but did not influenced the activity of spleenic
      T-lymphocytes with rossetting capacity and spleen cells forming Jerne plaques.
      There were significant skin and hepatic changes in microscopy. CONCLUSION: The
      studied dyes influenced the activity of immune system, increased skin and hepatic
      reactivity.

PMID- 20700995
TI  - [Polyomavirus BK and its role in associated kidney transplantation pathology].
AB  - In the last three decades kidney transplantation became a therapeutic approach in
      Romania but, unfortunately, the increasing of kidney transplantation procedures
      is related to an increasing rate of associated pathology such as Polyomavirus BK
      Associated Nephropathy (BKVAN). Studies published recently emphasize that BKVAN
      is a consequence of different risks factors, particular viral pathogenesis,
      humoral and cellular immunity and high doses of immunosuppressive drugs used for
      a long time are the main conditions that influence the BKVAN's evolution. Since
      there is no specific and effective treatment, optimal medical management is to
      diagnose nephropathy in early stages, to stop viral replication, limiting tubular
      lesions and prevent progress toward destruction by decreasing doses of
      immunosuppressive agents.

PMID- 20700996
TI  - [Chromogenic medium for detection of enterobacteria producing beta-lactamases in
      North-Eastern Romania].
AB  - We evaluated the performances and analyzed practicability of an ESBL-detecting
      chromogenic agar medium (chromID ESBL, bioMerieux) for the screening of ESBL
      production. MATERIAL AND METHODS: We have tested 112 enterobacteria strains,
      isolated in 2009 year, in North Eastern region of Romania. Each bacterial strain
      was cultured on a prepared plate chromogenic medium and the results were recorded
      after incubation at 37 degrees C for 18 to 24 h or, if necessary, for 48 h. We
      calculated the sensitivities, specificities, and positive and negative predictive
      values for this medium, using as gold standard ceftzidime or cefotaxime and
      clavulanate combination disks on Iso-Sensitest agar. K. pneumoniae ATCC 700603
      and E. coli ATCC 25922 were used as the positive and negative control for ESBL
      production, respectively. RESULTS: For all tested strains, the chromID ESBL agar
      showed a high sensitivity (97%), but a low specificity (66%). The positive and
      negative predictive values were 98% and 57%, respectively. The chromID ESBL had
      false-positive results for 2 confirmed ESBL-positive strains. CONCLUSION: The
      very good sensitivity of the chromID ESBL agar ESBL detection represent a
      convenient method for the recovery and identification of ESBL-producing
      enterobacteria.

PMID- 20700997
TI  - [Assessment of biochemical status in 464 persons form Bacau County].
AB  - The purpose of the study was to assess the biochemical status in a populational
      lot of 464 persons from Bacau County (urban and rural), through a minimal set of
      laboratory tests (glycemia, cholesterol, HDL-cholesterol, triglyceride). RESULTS:
      The average values from the rural lot are closed to the minimal limits of the
      values interval. The highest values (peaks) of glycemia in the rural lot are in
      the over 65 y.o. group, followed by great values registered in the 41-65 y.o.
      group. For the urban lot, the highest value is in the 41-65 y.o. group, that
      might be explained by the etiopathogenesis role of stress in the diabetes at
      young ages. Also, comparing the peaks in these two lots (rural vs. urban), we can
      notice that in the rural lot, the peaks are much higher than in the urban lot. A
      possible explanation might be a tighter monitoring of diabetes in urban vs. rural
      or a proper diet and lifestyle behavior in the urban lot.The averages values of
      cholesterol in the rural lot, for all groups of ages, are below the maximal
      admitted value (220 mg/dL) and the peaks are in the 41-65 y.o. group and over 65
      y.o., while in the urban lot the peaks are in the over 65 y.o. group. The minimal
      values of HDL cholesterol fraction which are inverse correlated with the risk of
      cardiovascular diseases emergence, are found in the extreme ages groups: 20-40
      y.o. and over 65 y.o. In the urban lot, the average values for the three age
      groups are closed and shows a low risk of cardiovascular diseases emergence
      (values up to 55 mg/dL). Regarding the levels of triglycerides, even if are below
      the maximal admitted values, in the rural lot, the peaks values are dispersed and
      are very high in the extreme ages groups: 20-40 y.o. and over 65 y.o., while in
      the urban lot peaks values are in the 41-65 y.o. group.

PMID- 20700998
TI  - [Comparative study concerning food intake in a group of people with dyslipidemias
      vs. a control group in the Targu Neamt area].
AB  - The aim of the study was to find a correlation between the consumption frequency
      of the main food groups and the presence of dyslipidemia as compared to a control
      group without dyslipidemias. MATERIAL AND METHOD: For this study we have
      considered a number of 678 people, divided in two groups: 339 with dyslipidemias
      and 339 without dyslipidemias, each of the two groups comprising 137 subjects
      from the rural area and 201 from the urban area, through the questionnaire
      method. RESULTS: The involved people have been questioned about the consumption
      of milk and related products (cheese), meat and related products (beef and pork),
      fish and related products and fruits. Regarding the fruit consumption, in the
      urban area, we have found slightly increased values in the witness group of the
      percentages of those who eat them daily and 4-6 times a week as compared to the
      group with dyslipidemias.

PMID- 20700999
TI  - [Clinical and microbiological study regarding surface antibacterial properties of
      bioactive dental materials].
AB  - In the new era of dentistry the coronal restoration materials must possess "bio
      active" features represented by fluor ions release, chemical adhesion and
      antibacterial agents. AIM: Our study aims to determine the surface antibacterial
      properties of glassionomer cements and compomers. MATERIALS AND METHOD: The study
      group included 64 patients with high cariogenic risk with 80 teeth with acute and
      chronic dental caries affecting proximal and occlusal dental surfaces. The teeth
      with cariogenic lesions were restored with zinc-oxide-eugenol (n=20),
      glassionomer cement GC Fuji Triage (n=20), glassionomer cement modified with
      resins Fuji II LC (n=20), compomer Dyract (n=20). DENTOCULT SM test (Orion
      Diagnostica, Finland) was used for bacterial analyses. The samples from bacterial
      biofilm were collected from the restorated dental surfaces (study group) and
      intact enamel surfaces (control group). The recorded data were processed using
      non-parametrical statistical tests. RESULTS: The lowest mean value of bacterial
      indices was recorded for glassionomer cement Fuji Triage (0.4), and Fuji II LC
      (1.2), material with highest surface antibacterial properties. The highest value
      (1.5) was recorded for compomer Dyract. The Kruskal-Wallis test proves the
      significant statistical differences between the three bioactive materials.
      CONCLUSION: The materials with bioactive features have the ability to inhibate
      the growth of Streptococcus mutans in bacterial biofilm to the surfaces of
      coronal restoration.

PMID- 20701000
TI  - [Epidemiological aspects of frontal edentation of child and adolescent].
AB  - Increasingly frequency of frontal edentation of children and adolescents, mainly
      because of dental caries and its complications and other diseases requires closer
      analysis and a reconsideration of therapeutic attitudes that must be carefully
      adapted and refined. AIM: To study the establishment of prevalence and incidence
      of child and adolescent frontal edentation, identifying its etiology and
      prospects of restoration of morpho-functional parameters affected, anchored in
      temporary or permanent solutions, according to age and morpho-functional
      development of the patient. MATERIAL AND METHODS: We studied a group composed of
      450 patients, aged between 8 and 19 years of age, diagnosed with frontal
      edentation of different etiologies. RESULTS: The two most common causes which are
      involved in producing edentation are odontal injuries and chronic periodontal
      disease. CONCLUSION: Etiology of frontal edentation has an esential part in the
      anatomoclinical shape of edentation, without evading the impact on bio-psycho
      social dimension of this clinical entity. The size of the edentation, the
      emotional impact for the child, and the medical aspects are very important in the
      decision of the right treatment for longtime.

PMID- 20701001
TI  - [Assessment of tooth wear depending on Smith and Knight index].
AB  - For the clinical diagnosis of tooth wear Smith and Knight have been suggested the
      index with the same name, the criteria for the quantification of the hard tissue
      loss being the size of the area affected and the depth of the defect. The aim of
      this study was to assess tooth wear depending on Smith and Knight index, on a
      group of 614 patients. MATERIAL AND METHOD: The criteria for the selection of the
      patients were the age more than 18 years old and the Smith and Knight index >0.
      RESULTS: The biggest proportion of tooth wear (47.3%) presented the value 2 of
      the Smith and Knight index. Most of the tooth wear with Smith and Knight index 3
      (54.4%) are abrasions, 71.4% of the tooth wear with Smith and Knight index 1 are
      attritions, and 20.3% of the tooth wear with Smith and Knight index 3 are
      erosions. High alcohol consumption is associated with deep tooth wear, exposing
      dentine (value 2 and 3 of the Smith and Knight index). Currently, various indices
      are used, making the comparison of the results of prevalence studies difficult.

PMID- 20701002
TI  - [The antimicrobial efficacy of an erbium laser on Streptococcus mutans. In vivo
      study].
AB  - This study was conducted in order to demonstrate the bactericidal effect of an
      erbium laser (Er,Cr:YSGG) on Streptococcus mutans, in vivo, at different laser
      power settings, obtaining sterile enamel surfaces with minimal tissue ablation.
      The practicians use the laser for the cutting effect on hard tissue to eliminate
      all the infected and affected enamel and dentine, without collateral damage on
      the pulp and for its bactericidal effect on cariogenic bacteria. MATERIAL AND
      METHOD: The study group included 132 superficial carious lesions, on 66 patients
      with ages between 6 and 20; a two-year study (January 2006 - November 2008)
      performed in a private practice. The carious lesions were ablated with an erbium
      laser with two types of tips. A sample of occlusal plaque was taken using a
      sterile swab, soaked in normal saline solution (before and after the
      preparation). RESULTS: Before the laser treatment, the percentage with high
      counts of Streptococcus mutans was 70% and low counts 30% (chi2 = 26.16 ; p <
      0.01). At the laser power of 4,5 watts, the zirconium tip (Z6) had a higher
      number of sterile culture (96,3%). The numbers of sterile cultures were higher at
      the laser power of 5 watts, with both tips: zirconium and sapphire, the
      percentage being equal: 91-92%.

PMID- 20701003
TI  - [Associated risk factors in developing oral manifestations in patients with blood
      dyscrasia].
AB  - The oral and dental complications arising in cancer patients can be attributable
      to the malignant disease itself and to the various modalities of cancer therapy.
      Up to 37.2% of all patients receiving cancer chemotherapy develop acute oral
      complications and up to 31.1% of all patients receiving cancer radiotherapy
      develop acute oral manifestations. Oral complications may result in significant
      morbidity, impaired nutrition, treatment delays, and dose reductions which are
      affecting the prognosis of the primary disease. MATERIAL AND METHOD: We
      investigated 312 cases of blood dyscrasia which 296 cases had oral manifestations
      (86.2%). They had a mean age of 40,6 years (range from 7 to 86 years). The male
      to female ratio was 1.0:0.75 (178/134). Data were statistically analyzed by t
      test, chi-square, Wilcoxon, Kruskal-Wallis and two-tailed exact Fischer, using
      the SPSS program, at a significance level of 5%. RESULTS: Oral complications are
      frequently encountered in patients receiving anticancer therapy and these
      complications may result in significant morbidity, treatment delays, dose
      reductions, and nutritional deficiencies. The acute effects of anticancer
      chemotherapy upon the oral cavity include mucositis, infection, hemorrhage,
      xerostomia and nutritional deficiencies. Patients which undergo radiotherapy,
      specific in head and neck carcinomas, display a 30-60% incidence of the oral
      manifestations. The antineoplastic therapy will interfere with the turnover of
      the epithelial cells, followed by mucosal injury, later by infections, due to
      indirect invasion of Gram-negative bacteria and fungal species, as most of the
      anti-cancer drugs cause immunological changes. CONCLUSIONS: The mucosal surface
      that is the oral cavity may provide insight into the immune function of the
      patient. Differential diagnosis is important as many disorders may manifest
      themselves similarly in the buccal area.

PMID- 20701004
TI  - [Posttherapeutic feed-back evaluation in oral rehabilitation].
AB  - The goal of this study was to assess the subjective post-therapeutic feedback for
      a group of patients in order to evaluate the possibility of including the psycho
      behavioral parameters into the analysis structure of an expert system. MATERIAL
      AND METHOD: 135 patients diagnosed with class I and II Kennedy edentation, aged
      between 40 and 89 years old, where clinically examined. All patients filled in
      structured questionnaires focused on psycho-behavioral parameters. RESULTS:
      Prosthetic treatment in oral rehabilitation improves subjective perception of
      facial aesthetic (66.86% total and moderate accord), psychological status (71.14%
      total and moderate accord) and of the social relations (77.47% total, moderate
      and low accord) but it is not subjective associated with the improving of general
      health (55.49% disagreement). CONCLUSIONS: We can establish statistical support
      correlation between psycho-behavioral parameters and therapeutic solutions
      applied in oral rehabilitation, correlation that can be later quantified and used
      in the development of an expert system.

PMID- 20701005
TI  - [Management and prevention of oral manifestations for blood dyscrasia and viral
      pathology].
AB  - The study outlines the dentist's attitude in dealing with two of the many serious
      diseases throughout the body, HIV infection and acute leukemia. Many systemic
      diseases have oral manifestations which may appear at the beginning of any
      developed pathology, thus early detection can occasionally occur at the dental
      clinic. Gingival lesions are the most common oral phenomenon known for leukemia
      and HIV infection. In this case an early detection of pathology at the dental
      clinic was based on an uncommon and single presenting sign of massive spontaneous
      gingival bleeding. The objectives are demonstrate this unusual sign of blood
      dyscrasia and HIV infection in oral cavity and establishing management and
      prevention of oral manifestations for blood dyscrasia and pathology with viral
      etiology. MATERIAL AND METHOD: We investigated 225 cases had pathology with viral
      etiology. The patients entered the study HIV/AIDS in Botosani, Suceava, Neami
      during 2004-2008. All patients had a detailed medical history and examination as
      well as a thorough oral examination, which were all done without prior knowledge
      of the patient's HIV serostatus. RESULTS: Oral disease is frequently associated
      with HIV. While nearly all oral disorders associated with HIV infection also
      occur in other conditions characterized by immunosuppression, no other condition
      is associated with as wide and significant a spectrum of oral disease as is HIV
      infection. Many HIV associated oral disorders occur early in HIV infection, not
      infrequently as the presenting sign or symptom. Thus, early detection of
      associated oral disease should, in many cases, result in earlier diagnosis of HIV
      infection. Likewise, awareness of the variety of oral disorders which can develop
      throughout the course of HIV infection, and coordination of health care services
      between physician and dentist, should improve overall health and comfort of the
      patient. This paper reviews the clinical, diagnostic and therapeutic aspects of
      HIV associated oral disorders. CONCLUSIONS: Diseases with a particular viral
      etiology infectiousness have a special resurgence. For the dentist, their
      recognition has a particularly importance for the quick and accurate
      determination of the diagnose and for the establishing, together with the
      infectious disease physician, of the appropriate treatment. Working with the
      department of epidemiology is useful to define the preventive measures among the
      community.

PMID- 20701006
TI  - [Prevention of spinal disorders in dentistry].
AB  - Professional activity in dentistry account for excessive request of the spine and
      peripheral joints. MATERIAL AND METHOD: We performed an observational prospective
      study on ten physicians (six women, four men) aiming to evaluate the time used in
      vicious positions during a working day and to establish a specific kinetic
      program directed to relaxation and rebalancing lumbo-abdomino-pelvic muscles. The
      working time in a typical day either using orthostatic or sitting position was
      assessed according to a standard protocol. RESULTS: Left dorsal scoliosis with
      rotation lasting over 97 minutes of daily working time, sinistro-concave dorsal
      scoliosis with a typical duration of 42.5 minutes, dextro-concave kyphoscoliosis
      with a mean time of 37 minutes and dorsal scoliosis with right rotation lasting
      31 minutes were reported. Moreover, both left and right rotations were
      demonstrated during the working time accounting for about 22.5 minutes and 29
      minutes respectively, while a lesser time deal with the side of right-left
      uncombined movement. CONCLUSION: Almost three quarters of working time (71%)
      takes place in vicious positions, suggesting that, unfortunately, the ergonomic
      position is seldom maintained in current dentistry practice. A complex
      rehabilitation program is therefore mandatory in order to prevent muscle
      imbalance.

PMID- 20701007
TI  - [Generalized gingival enlargement--early clinic manifestation in acute leukemia.
      Case report].
AB  - Leukemia is a hematological disorder arises from a hematopoietic stem cell
      characterized by a disordered differentiation and proliferation of neoplastic
      cells. Rapidly forming generalized gingival hyperplasia is usually the first sign
      of this disease (especially in acute forms). This case report describes a 54-year
      old female who presented rapid gingival enlargement in only three weeks time,
      heralding the presence of acute monocytic leukemia (AML-FAB M5). The patient was
      immediately referred for hematologic management, but died five weeks later.
      Dentists and generalists should always be on guard to observe any oral
      manifestations that may lead to the early diagnostic of systemic diseases.

PMID- 20701008
TI  - Researches of the nitrates and nitrites in some well waters from rural area in
      correlation with methoglobinemia morbidity.
AB  - Ground water is a major source of public supply for the rural population and in
      some areas, it is only source of available water. It is well known the toxic
      action of nitrate upon organisms, by formatting methemoglobin and N-nitroso
      compounds. MATERIAL AND METHODS: In this study it was investigated the presence
      of nitrates and nitrites in same well waters, mountain and hill areas in Neamt
      district. The chemical parameters were carried out by following standard methods.
      The statistical analysis includes descriptive statistics of the water quality
      parameters. RESULTS: It is noticed high values of the nitrate concentrations,
      over Maximum Admissible Concentration (MAC), explained by excessive use of
      agricultural synthetic fertilizer and telluric nitrogen. It was registered a
      number of 38 cases of methemoglobinemia in small children with artificial
      nutrition, all cases from hill area. The maximum methemoglobin level was 60% and
      the minimum value of nitrate concentration in the water samples was 396 mg NO3
      /L. CONCLUSIONS: We established a direct correlation between the level of
      methemoglobin and the nitrate concentrations in water samples. It is recommended
      the use well waters with maximum 48 mg/L nitrates content.

PMID- 20701009
TI  - [Regulation of cellular-mediated immunity by Chenopodi boni henrici herba
      polysaccharides in hens].
AB  - The immunomodulatory effect of polysaccharides from Chenopodium bonus-henricus
      herba was tested on adult hens. MATERIAL AND METHOD: Blood samples were harvested
      aseptically by punction of brachial vein; ability of circulating phagocytes was
      assessed by the carbon particles phagocytosis test in vitro; while reactivity of
      peripheral lymphocytes was evaluated by lymphocytes transformation assay in
      vitro. Polysaharides were dissolved in saline solution and filtered throughout
      Millipore. RESULTS: Phagocytic indexes (at 15 and 39 minutes) are variable
      according to polysaharides concentration; phagocytosis increased at 15 minutes
      for 40 microg/mL and 60 microg/mL, while for 30 minutes the phagocytic index
      decreased. In lymphocytes transformation assay, Chenopodium bonus-henricus
      polysaharides, alone, shown no stimulatory effect, and together to the classic
      mitogen, their influence was variable, but not statistical significant results
      were seen. CONCLUSION: Polysaccharides have inconstant effect on phagocytosis,
      and mainly inhibitory role on lymphocytes proliferation.

PMID- 20701010
TI  - Chemical composition of the essential oil of Salvia officinalis L. from Romania.
AB  - The quantitative and qualitative analysis of essential oils obtained from Salvia
      officinalis L. (Lamiaceae) cultivated in Romania is reported in this paper.
      MATERIAL AND METHODS: The essential oils were obtained from fresh and dried
      material harvested from plants cultivated in Cluj (Romania) and from 2 commercial
      samples, by hydrodistillation. The essential oils were analysed by GS-MS.
      RESULTS: 12 compounds were found in each oil, 9 of them being common in all
      samples. The alpha-thujone was the major compound in all analysed oils (31.23
      52.86%), followed by camphor and viridiflorol. Chemically, the oxygenated
      monoterpenes are present in highest quantity (49.78-79.2%). CONCLUSIONS: The
      monoterpenoid ketones' presence (a-thujone, a-thujone, camphor) in high amounts
      in the essential oils of Romanian sage may develop toxicity for these products
      and may limit their medicinal use.

PMID- 20701011
TI  - [Assessment of Cefixime stability, raw material used for pharmaceutical forms].
AB  - In this paper we studied the stability of cefixime, a raw material used for
      pharmaceutical forms. MATERIAL AND METHOD: Quantitative analysis was made by
      using a UV spectrometric method. RESULTS: We established the cefixime content
      after exposing on different conditions of temperature and environment. The
      obtained results demonstrated that cefixime is stable at environmental
      temperature and degrades fast and strong in aggressive environments.

PMID- 20701013
TI  - [Screenings, between clinical and public health].

PMID- 20701014
TI  - [Screening: principles and methods].
AB  - The concept of early detection to then intervene and improve the prognostic seems
      straightforward. Applied to asymptomatic subjects, this concept--screening--is
      rather complex. This review presents the rational and fundamental principles of
      screening. It underscores the fundamental principles related to the disease and
      to the screening test considered, the importance of considering screening as a
      program rather than a test only, and the validity of measures used to evaluate
      the efficacy of screening. Lastly, it reviews the most frequently bias
      encountered in screening studies and interpretations.

PMID- 20701012
TI  - Formulation of creams with betamethasone dipropionate: evaluation of chemical
      stability.
AB  - The aim of this study was to investigate how the different excipients influenced
      the chemical stability of betamethasone dipropionate in creams. The chemical
      stability was evaluated by analyzing betamethasone related substance content.
      Transcutol is the excipient ensuring maximum stability to betamethasone.
      Incompatibilities between betamethasone dipropionate and hexylene glycol were
      observed. The pH values in the weak acid range confer chemical stability to
      betamethasone.

PMID- 20701015
TI  - [The example of cystic fibrosis to highlight the complexity of genetic
      screening].
AB  - Various institutions and countries often reach different conclusions about the
      utility of introducing a newborn screening test in the general population. This
      paper highlights the complexity of population screening including genetic tests.
      Using the example of cystic fibrosis genetic screening, for which a Swiss Working
      Group for Cystic Fibrosis is currently evaluating the pertinence, we outline that
      screening recommendations are often based more on expert opinion and emerging new
      technologies rather than on evidence. We also present some ethical and economic
      issues related to cystic fibrosis genetic screening.

PMID- 20701016
TI  - [Chronic kidney disease: screening attitude and practice in the absence of
      randomized controlled trials].
AB  - Given the increasing prevalence of chronic kidney disease (CKD), early detection
      has been proposed. Some organizations recommend CKD screening. Yet, the efficacy
      of CKD screening is unknown given the absence of randomized controlled trial
      conducted so far. While CKD screening tests (e.g., glomerular filtration rate)
      are simple and inexpensive, CKD screening can only be justified if it reduces CKD
      related mortality and/or CKD-related morbidity compared to no screening. In
      addition, CKD screening must provide more benefits than risks to the participants
      and must be cost-effective. Based on observational studies and cost-effectiveness
      models, CKD screening has to be proposed to high risk population (patients with
      hypertension and/or diabetes) but not to the general population.

PMID- 20701017
TI  - [From guidelines for screening to their (poor) implementation: the case of the
      abdominal aortic aneurysm].
AB  - Following the evidence of benefits of ultrasound screening for abdominal aorta
      aneurysms (AAA), several guidelines support this screening in population. Beyond
      the prompt diagnosis of AAA prior to its rupture of grim vital prognosis, small
      AAA can beconsidered as a prognostic marker for cardiovascular diseases (CVD).
      Yet, its detection is an opportunity for secondary prevention to reduce CVD
      mortality. Despite, these guidelines are poorly applied: systematic screening
      campaigns are infrequent, making the screening of family physicians
      responsibility. While the major benefit from this screening strategy is to reduce
      AAA-related death (but only trivial effect on long-term total mortality), this
      explains only partially the lack of guidelines implementation. The reasons of the
      poor implementation of these guidelines are discussed herein.

PMID- 20701018
TI  - [Cancer screening in clinical practice: the value of shared decision-making].
AB  - Shared decision-making approach to uncertain clinical situations such as cancer
      screening seems more appropriate than ever. Shared decision making can be defined
      as an interactive process where physician and patient share all the stages of the
      decision making process. For patients who wish to be implicated in the management
      of their health conditions, physicians might express difficulty to do so. Use of
      patient decision aids appears to improve such process of shared decision making.

PMID- 20701019
TI  - [ECG in an elderly patient: trigeminal rhythm].

PMID- 20701020
TI  - [Recidivism of sexual crimes: what can we do? (1)].

PMID- 20701021
TI  - [Bioethics: Kant is finally reduced to silence? (3)].

PMID- 20701022
TI  - [Normality of the female libido? (2)].

PMID- 20701023
TI  - [Growing old].

PMID- 20701024
TI  - [Effect of melatonin on activity of superoxide dismutase (CuZn-SOD) in
      erythrocytes of patients during short- and long-term hypokinesis].
AB  - INTRODUCTION: Short- or long-lasting hypokinesis is to a large degree the
      consequence of negative habits of human beings towards a comfortable and more
      sedentary lifestyle. The period of decreased physical activity can cause
      disturbance in the balance between systemic processes of the oxidation and
      reduction, which leads to an increase in reactive oxygen species (ROS) and
      oxidative stress generation. The aim of the study was to determine the effect of
      melatonin administration on the cellular superoxide dismutase (CuZn-SOD) activity
      in red blood cells of patients with short- and long-term hypokinesis as compared
      to the group of subjects with normal physical activity. MATERIAL AND METHODS: The
      study included 33 subjects with immobilization. The study group was divided into
      two subgroups (depending on hypokinesis duration): group A: 15 subjects
      classified for total hip alloplasty (a short-lasting decrease in physical
      activity); group B: 18 subjects suffering from multiple sclerosis or the stroke
      of brain (the long-term hypokinesis). The control group (group C) comprised 17
      subjects with normal physical activity. Melatonin was applied at a dose of 5 mg
      daily, one hour before sleep. The CuZn-SOD activity in red blood cells was
      determined, according to the Misra and Fridovich method, in two periods: 1) on
      the first day, 2) on the 10th day (group A), and 30 days (group B) after
      melatonin administration. RESULTS: A slight increase in CuZn-SOD activity (+3.1%)
      was observed in group A 10 days after alloplasty and melatonin administration as
      compared to group B, where a considerable rise in the enzyme activity (+23.3%)
      was found 30 days after rehabilitation and melatonin supplementation. The average
      CuZn-SOD activity in both investigative groups was lower than that in the
      controls (group C). CONCLUSIONS: It was estimated that the short- and long
      lasting hypokinesis leads to an increase in ROS generation, what is confirmed by
      the increase in CuZn-SOD activity. The results of the study on superoxide
      dismutase activity indicate that oral administration of melatonin for the period
      of 30 days has a more favorable influence on antioxidative processes than 10
      day's melatonin intake.

PMID- 20701025
TI  - [Pharmacokinetics of digoxin in hyperthyroidism. Effect of methimazole].
AB  - INTRODUCTION: Cardiovascular abnormalities may be the only manifestations of
      overt hyperthyroidism. In patients with heart failure and atrial fibrillation
      digoxin can be beneficial in controlling the symptoms and signs, but hyperthyroid
      patients show an impaired response or even resistance to digoxin treatment. The
      aim of the study is to establish: 1. Are there any differences in the
      pharmacokinetics of a single oral dose of digoxin between hypertyroid and
      euthyroid patients? 2. Does simultaneous administration of digoxin and
      methimazole affect the pharmacokinetics of a single oral dose of dogoxin? 3. Does
      methimazole-induced euthyroidism change the pharmacokinetics of a single oral
      dose of digoxin? MATERIAL AND METHODS: The subject of the study were 28 patients
      with hyperthyroidism and 15 healthy persons. We evaluated the pharmacokinetics of
      a single oral dose of digoxin. Moreover we evaluated pharmacokinetics of a single
      dose of digoxin after simultaneous administration of digoxin and methimazole in
      12 patients and 12 methimazole treated patients werere-assessed once they had
      become euthyroid. RESULTS: Hyperthyroid patients showed significantly lower serum
      digoxin concentrations, shorter T1/2 beta and a significantly smaller area under
      the concentration curve (AUC) that the control group. Administration of
      methimazole did not affect digoxin pharmacokinetics. CONCLUSIONS: In hyperthyroid
      patients: 1. the pharmacokinetics of a single oral dose of digoxin does differ
      from that observed in healthy subjects. 2.methimazole do not alter digoxin
      pharmacokinetics.

PMID- 20701027
TI  - Exacerbated course of atrophoderma of Pasini and Pierini in patient with
      papillary cancer of the thyroid gland.
AB  - Atrophoderma of Pasini and Pierini is a benign cutaneous atrophy skin to morphea
      en plaques on repression and is considered as systemic sclerosis-like disorder. A
      case of female patient with atrophoderma of Pasini and Pierini in whom rapid
      eruption of new plaques was found after many years of stable disease in
      described. Papillary cancer of the thyroid gland was diagnosed and acceleration
      of atrophoderma should be considered as paraneoplastic syndrome.

PMID- 20701026
TI  - Association between lipids and fibrinogen levels and ischemic stroke in the
      population of the Polish children with arteriopathy and cardiac disorders.
AB  - INTRODUCTION: The ischemic stroke is a rare problem in childhood. Cardiac
      problems, arteriopathy, coaguopathies or dyslipidemia are traditional risk
      factors for stroke. The aim of the present study was to assess the relations
      between levels of lipids and fibrinogen and stroke among Polish children.
      MATERIAL AND METHODS: We studied 75 patients (mean age: 8.24 +/- 5.56) and 71
      healthy children (mean age: 10.32 +/- 5.7). The diagnosis of ischemic stroke was
      established with the WHO definition. RESULTS: Serum triacylglycerols level and
      plasma fibrinogen level may be considered as risk factors for childhood stroke
      (p=0.004, OR=7.01 and p=0.024, OR=2.16, respectively). In the subgroup of stroke
      children with cardiac problems the triacylglycerols level is also the risk factor
      for stroke (p=0.006, OR=7.14). CONCLUSIONS: Levels of triacylglycerols and
      fibrinogen again differentiated the subgroup of children with neurological
      deficits from controls. In conclusion, the levels of triacylglycerols and
      fibrinogen are important risk factors in the etiology of stroke.

PMID- 20701028
TI  - [The role of laser CO2 in proctology].
AB  - There is presented our experience in surgical hemorrhoids and condylomata
      acuminata treatment using CO2 laser. There were 289 operations on 198 patients in
      outpatient clinic. There were 4 cases of anal fissure and no postoperative
      bleeding during postoperative period. This work is demostrating that adaptation
      of the laser CO2 makes many advantages to the classic operation of Milligan ad
      Morgan: simplification of the surgical technique easy post-operative course, no
      hospitalisation and quicker return to work. Complications are rare and excellent
      results are noted. Laser CO2 treatment is considered one of the alternatives to
      conventional treatment, but the surgeon needs to be aware of laser hazards.

PMID- 20701029
TI  - Carpal tunnel syndrome as the early symptom of rapidly progressive systemic
      sclerosis in men.

PMID- 20701030
TI  - [One aspect of cancer prevention for the final section of the colon].

PMID- 20701031
TI  - MedChi's accomplishments are great in a short period of time.

PMID- 20701032
TI  - Ergs and Joules, or an ounce of anger is worth a world of cure.

PMID- 20701033
TI  - Dignity for patients at the end of their lives.

PMID- 20701034
TI  - Long-awaited health care reform enacted in Maryland. Assignment of benefit
      legislation becomes law.

PMID- 20701035
TI  - Report on the Maryland General Assembly session.

PMID- 20701036
TI  - How health system reform affects patients.

PMID- 20701037
TI  - How the passage of federal health system reform legislation impacts your
      practice.

PMID- 20701038
TI  - Comfort care.

PMID- 20701039
TI  - Healing instrument. Beat of the drum.

PMID- 20701040
TI  - Focal dystonia. Changing his tune.

PMID- 20701041
TI  - The artist as physician.

PMID- 20701042
TI  - More than pretty pictures.

PMID- 20701043
TI  - The creative arts therapies: making health care whole.
AB  - The creative arts therapies are six fields that combine artistic expression with
      psychotherapy to promote healing, wellness, and personal change. Although they
      are well-established fields, they are garnering renewed attention with the recent
      focus on health care and the arts. This article describes these fields and
      provides information about the training and professional standards of creative
      arts therapists and examples of how these therapies are being used in health care
      settings.

PMID- 20701045
TI  - Who does what on wards debate rages as hands-on time dwindles.

PMID- 20701044
TI  - The future of personal health records: a summary of a roundtable discussion.
AB  - In 2009, the Institute for Clinical Systems Improvement held a roundtable on
      personal health records (PHRs). Participants shared their thoughts about which
      features and functions are desired in a PHR, areas that need further exploration,
      and ways PHRs could make health care more efficient and effective. This article
      summarizes those discussions.

PMID- 20701046
TI  - Queen of the screen.
AB  - Advising programme makers on breast cancer storylines has fired Victoria Harmer's
      enthusiasm to do more media work, and so raise awareness.

PMID- 20701047
TI  - Community care in a hospital setting.
AB  - The concept of a community hospital has taken off in a new direction in Oxford.
      Rehabilitation is now provided within the acute hospital.

PMID- 20701048
TI  - Fear of falling.
AB  - The ataxias are a complex group of conditions for which there is no cure. But
      specialist care can help with the symptoms.

PMID- 20701049
TI  - Living life with lupus.
AB  - Lupus affects at least one in 800 women in the U.K., but its diagnosis is often
      complicated by vague symptoms.

PMID- 20701050
TI  - Confused guidance.

PMID- 20701051
TI  - Track and trigger system for use in community hospitals.
AB  - AIM: To adapt and promote a relevant track and trigger system based on modified
      early warning systems (MEWS) for use in rural community hospitals in Powys,
      Wales. METHOD: Track and trigger systems, including MEWS, were reviewed, compared
      and developed by senior nursing and medical staff using PDSA (Plan Do Study Act)
      cycles. RESULTS: A track and trigger system was developed, piloted and rolled out
      to all ten community hospitals in Powys. The system is not only used to monitor
      inpatients, but is also useful in determining appropriateness of patient transfer
      to district general hospitals. CONCLUSION: The track and trigger scoring system
      has proved useful in assessing patients and alerting staff if their condition is
      deteriorating. It has ensured, when necessary, timely, appropriate and safe
      transfer of patients to the district general hospital. The scoring system has
      been extended to determine appropriateness of accepting patients from the
      district general hospital to the community hospital.

PMID- 20701052
TI  - Using google scholar to conduct a literature search.
AB  - This article provides information about conducting a literature search on the
      Google Scholar website. The article briefly describes how to narrow or expand a
      search and how to find non-journal literature. Although Google Scholar is not
      without limitations, it offers a practical starting point for a literature
      search.

PMID- 20701053
TI  - HIV and AIDS.

PMID- 20701054
TI  - Issues affecting concordance with leg ulcer care and quality of life.
AB  - This article examines the issues that influence patients' concordance with leg
      ulcer treatment regimens and the effect this may have on quality of life. Nurses
      need to have a good understanding of the physical and psychosocial factors that
      affect patients' concordance with treatment and how any issues can be resolved to
      enable successful patient-professional partnership, effective care planning and
      delivery, and better patient outcomes.

PMID- 20701055
TI  - Tissue viability in mental health.
AB  - Mental health and tissue viability are not usually associated with each other,
      yet people with mental health problems may be more susceptible to developing
      wounds, particularly those who engage in self-harm. This article focuses on the
      management difficulties experienced by staff caring for patients with mental
      health problems presenting with wounds within Leicestershire Partnership NHS
      Trust.

PMID- 20701056
TI  - Holistic care in practice.

PMID- 20701057
TI  - Skills gap set to widen.

PMID- 20701058
TI  - A flexible career option.

PMID- 20701059
TI  - Implementation of new telemedicine requirements delayed until March 2011.

PMID- 20701061
TI  - Change in leadership at JCR and JCI.

PMID- 20701060
TI  - Correction: Missing requirement for disease-specific care and advanced
      certifications.

PMID- 20701062
TI  - Preventing violence in the health care setting.

PMID- 20701063
TI  - Modifications to S3 report.

PMID- 20701064
TI  - Assessment of fluorescence in situ hybridization and hybrid capture 2 analyses of
      cervical cytology specimens diagnosed as low grade squamous intraepithelial
      lesion for the detection of high grade cervical intraepithelial neoplasia.
AB  - OBJECTIVE: To assess Hybrid Capture 2 (HC2) and fluorescence in situ
      hybridization (FISH) for the detection of cervical intraepithelial neoplasia 2 or
      worse (CIN 2+) in patients with a cytologic diagnosis of low grade squamous
      intraepithelial lesion (LSIL). STUDY DESIGN: Residual samples from 115 LSIL
      diagnosed cervical cytology specimens were evaluated by high-risk human
      papillomavirus (HR-HPV) HC2 testing and FISH using biotin-labeled probes to HR
      HPV and chromosomal probes to 3q26 (TERC) and 8q24 (CMYC). A cervical biopsy
      diagnosis of CIN 2+ was considered as evidence of high grade disease. RESULTS:
      The positive and negative predictive values of HC2 and FISH for detecting
      patients with CIN 2+ were 32% vs. 37% and 100% vs. 93%, respectively. The
      sensitivities of HC2 and FISH for CIN 2+ were not significantly different (100%
      vs. 90%, p = 0.25), while the specificity of HC2 was significantly lower than
      that of FISH (28% vs. 48%, p=0.003). FISH diagnosed fewer specimens as positive
      as compared to HC2 (62% vs. 79%). CONCLUSION: These preliminary data suggest that
      FISH testing may be useful for determining which patients with LSIL are most
      likely to have CIN 2+ on clinical follow-up.

PMID- 20701065
TI  - Fecal cytology in conjunction with immunofecal occult blood test for colorectal
      cancer screening.
AB  - OBJECTIVE: To develop a simple method to extract and analyze the cytomorphology
      of epithelial cells from fecal samples and to compare the efficacy of fecal
      cytology with the immunofecal occult blood test (IFOBT) in colorectal cancer
      screening. STUDY DESIGN: Fecal cytology and IFOBT were performed on fecal samples
      obtained from 41 patients with colorectal cancer; 34 patients with a small,
      single adenoma (<0.5 cm); and 20 without abnormality. The samples were obtained
      prior to colonoscopic examination. For fecal cytology, epithelial cells were
      exacted through filtration, centrifugation and cytocentrifugation and stained
      with hematoxylin-eosin prior to morphologic analysis. RESULTS: Fecal cytology and
      IFOBT test had similar levels of sensitivity for detecting colorectal cancer
      (75.6% vs. 68.3%, respectively), but fecal cytology had higher specificity than
      IFOBT (100% as compared to 85.2%, respectively, p<0.05 by chi2 test). Seven of 41
      colorectal cancer patients (17.1%) with negative IFOBT were positive by fecal
      cytology analysis. Combining fecal cytology with the IFOBT test in an either/or
      scenario significantly increased the sensitivity of IFOBT test to 92.68% for
      colorectal cancer detection (p<0.05 by chi2 test) without compromising the
      specificity. CONCLUSION: Fecal cytology augments the sensitivity of IFOBT in
      detecting colorectal cancers, and combining fecal cytology and IFOBT may provide
      an important simple and cost-effective alternative for colon cancer screening.

PMID- 20701066
TI  - Sorafenib's inhibition of prostate cancer growth in transgenic adenocarcinoma
      mouse prostate mice and its differential effects on endothelial and pericyte
      growth during tumor angiogenesis.
AB  - OBJECTIVE: To evaluate Sorafenib's efficacy (60 mg/kg/d per os) in preventing the
      transformation of high grade prostate intraepithelial neoplasia (HGPIN) into
      adenocarcinoma (ADC) and in inhibiting the onset and progression of poorly
      differentiated carcinoma (PDC) in transgenic adenocarcinoma mouse prostate
      (TRAMP) mice. STUDY DESIGN: Forty-four TRAMP mice were randomly divided into 2
      groups of 22 and assigned to daily treatment by gavage with vehicle only or
      Sorafenib from the 10th to the 26th week of age. At 26 weeks of age the mice were
      killed, and their genitourinary apparatus was removed and examined by histology,
      immunohistochemistry and confocal microscopy. RESULTS: Sorafenib reduced HGPIN
      growth and progression to ADC and was probably also effective in PDC inhibition.
      The major effect of Sorafenib was on tumor angiogenesis. Interestingly a
      dissociation between endothelial cells and pericytes was noted in treated PDC
      since inhibition of pericyte recruitment was less complete than that of
      endothelial cells. CONCLUSION: Sorafenib's potent antiangiogenic action may be
      supposed to be exerted primarily by inhibiting endothelial proliferation and
      sprouting, whereas its inhibition of pericyte recruitment and maturation is less
      complete. These observations suggest that Sorafenib's effects could be improved
      by the joint employment of substances capable of interfering with the recruitment
      and organization of pericytes.

PMID- 20701067
TI  - Ploidy status of odontogenic tumors with epithelial components.
AB  - OBJECTIVE: To evaluate the DNA ploidy status of different histologic types of
      odontogenic tumors (OTs) with epithelial components. STUDY DESIGN: Biopsy
      materials of cases that were diagnosed as ameloblastoma or OT with epithelial
      component were retrieved from archives. Routine hematoxylin-eosin sections were
      prepared from paraffin-embedded tumor materials. A monolayer cell suspension was
      prepared from tumor cells that were enzymatically and mechanically isolated from
      biopsy material. DNA content of the nuclei was assessed on Feulgen-stained
      monolayer cell preparations with automated image cytometry. Ploidy assessments
      were done according to DNA indices. RESULTS: Sixty cases of OT were evaluated.
      All cases had epithelial components. There were 30 pure ameloblastomas and 30
      other OTs with epithelial components. All cases were diploid in DNA assessment.
      CONCLUSION: The current study showed that ameloblastomas and other OTs with
      ameloblastic epithelial components are diploid. To the best of our knowledge,
      this was the largest study to evaluate the DNA ploidy status of OTs.

PMID- 20701068
TI  - Comparison between incidentally and clinically detected prostate cancer:
      implications for prostate cancer screening programs and focal therapy.
AB  - Incidental prostate cancer is frequently observed in radical cystoprostatectomy.
      The majority are considered clinically insignificant. The relationship between
      clinically and incidentally detected cancer is uncertain. However, the results of
      the analysis of incidentally detected prostate cancer could be of paramount
      importance when trying to understand the type of cancers discovered in screening
      programs and/or identify the ideal candidates for focal therapy.

PMID- 20701069
TI  - Preliminary comparison of tumor biologic factors in breast carcinomas from
      Australian and Chinese women.
AB  - OBJECTIVE: To compare the morphologic and immunohistochemical properties of
      breast carcinomas from Chinese and Australian women in order to define possible
      biologic differences between these carcinomas. STUDY DESIGN: Three hundred cases
      of breast carcinomas were assessed for histologic and immunophenotypic
      characteristics from the pathology archives of the Changhai and St. Vincent's
      Hospitals. RESULTS: The Chinese women had proportionally more grade 2 and 3
      tumors, whereas Australian women had a higher proportion of grade 1 tumor. There
      was a higher proportion of younger patients with a larger tumor and patients with
      lymph node involvement in the Chinese group as compared with Australian women.
      There was no difference in rate of estrogen receptor positive tumors between the
      2 groups. p53 Expression was statistically more common with less cyclin D1
      expression in Chinese as compared with Australian women. CONCLUSION: This study
      indicates that both inherent tumor biology and stage at presentation influence
      adversely affect the outcome of breast carcinoma in Chinese compared as with
      Australian women.

PMID- 20701070
TI  - Importance of flow cytometric analysis of serous effusions in the diagnosis of
      hematopoietic neoplasms in patients with prior hematopoietic malignancies.
AB  - OBJECTIVE: To determine the criteria for the use of immunophenotyping by flow
      cytometry (FCM) in the diagnosis of hematopoietic lesions. STUDY DESIGN: A
      retrospective review of 89 consecutive body fluid specimens with concurrent FCM
      analysis during 2001 to 2006 was performed. The cytopathologic diagnosis was
      compared with the final diagnosis as modified by subsequent FCM. RESULTS: The
      cytopathologic diagnosis was benign in 61 cases (69%), atypical in 20 cases (22%)
      and malignant in 8 cases (9%). In patients without any prior clinical history,
      FCM study was positive in 2 cases and negative in 49 cases. In these patients,
      the working cytopathologic diagnosis was modified from benign/atypical to
      malignant in 2 (11%) cases and atypical to benign in 11 (33%) cases. In patients
      with a prior clinical history, FCM was positive in 23 cases and negative in 15
      cases. CONCLUSION: FCM studies were helpful in the cytopathologic diagnosis in
      35% of body fluid specimens, permitting appropriate cancer staging and
      management. In the absence of a prior clinical history, immunophenotyping by FCM
      in body fluid specimens should be ordered after adequacy studies when there is
      cytologic atypia or a strong suspicion of malignancy on the cytopathologic
      diagnosis.

PMID- 20701071
TI  - Protective effects of N(G)-nitro-L-arginine methyl ester and metallothioneins on
      excess nitric oxide toxicity in trinitrobenzene sulfonic acid-induced rat
      colitis.
AB  - OBJECTIVE: To evaluate the protective effects of N(G)-nitro-L-arginine methyl
      ester (L-NAME) and metallothioneins on excess nitric oxide toxicity in
      trinitrobenzene sulfonic acid (TNBS)-induced rat colitis. STUDY DESIGN: In this
      study, 70 rats were assigned to 7 groups of controls, and colitis was induced
      with 120 mg/kg TNBS, 35 mg/kg L-NAME, and 1 and 2 mg/kg metallothionein 1 (MT1)
      and metallothionein 2 (MT2), respectively. A day after the administration of
      TNBS, L-NAME, MT1 and MT2 were given intraperitoneally for 3 days to the
      experimental groups. After the administration of TNBS, dissections of the rats in
      the L-NAME, MT1 and MT2 groups were performed at 3-day periods under ether
      anesthesia, and whole blood, bone marrow and colon were obtained. RESULTS: On the
      third day, red and white blood cell values were increased, while platelet and
      bone marrow granule cells decreased in the L-NAME- and TNBS-induced group. On the
      third day, all the blood values increased in MT1 (1 and 2 mg/kg) and MT2 (1 and 2
      mg/kg) in the TNBS-administered groups. Histologic findings were macroscopic
      score, ulcer, loss of mucous cells, crypt abscess, inflammatory cyst, mucosa
      atrophy, edema, vascular dilatation and induced nitric oxide synthetase, which
      increased in the descending colon in the colitis rats, while it was decreased
      rats given L-NAME, MT1 and MT2 administration. CONCLUSION: The results suggest
      that MT1 and MT2 are more effective in protecting against the toxic effects of
      excess nitric oxide as compared with L-NAME in the colitis rats.

PMID- 20701072
TI  - Urachal urothelial carcinoma diagnosed at a radical prostatectomy operation: a
      case report.
AB  - BACKGROUND: Urachal carcinomas are rare tumors, and the majority of them are
      adenocarcinomas. Up to now, only 21 urachal urothelial carcinomas (UCas) have
      been reported. Here, we describe a case of high grade UCa arising from the
      urachal remnants. CASE: A 66-year-old man presented with voiding difficulties.
      Prostate specific antigen (PSA) was 5.46 ng/mL. Prostatic adenocarcinoma (PCa)
      (Gleason score 6) was diagnosed by needle biopsies. After the diagnosis of high
      grade, muscle invasive UCa with intact mucosa on frozen examination of the dome
      of bladder wall during the radical prostatectomy operation (RPO), partial
      cystectomy was performed. Microscopically, among the tumoral islands, cystic
      structures lined by cells with a benign appearance, which are considered urachal
      remnants, were noted. Cytokeratin 7 and high-molecular-weight cytokeratin were
      strongly positive, PSA and carcinoembryonic antigen were negative. Radiotherapy
      was given for both UCa and PCa. Six months after the diagnosis, an
      undifferentiated tumor was detected in a bladder transurethral resection
      specimen; thus, chemotherapy was given. After 1 course of chemotherapy, the
      patient was doing well. CONCLUSION: The origin of urachal carcinomas is usually
      obscured as it is a highly invasive carcinoma. The patient presented here was
      diagnosed incidentally during RPO. Although the stage was advanced, the tumor was
      detected before urachal remnants were destroyed. The treatment choice for urachal
      carcinomas is cystectomy. Adjuvant chemotherapy and radiotherapy are
      controversial.

PMID- 20701073
TI  - Quantitative analysis in canine cutaneous mast cell tumors.

PMID- 20701074
TI  - Identification of annexin A13 as a regulator of chemotherapy resistance using
      random homozygous gene perturbation.
AB  - OBJECTIVE: To utilize a powerful new technology for target discovery, Random
      Homozygous Gene Perturbation (RHGP), and to identify novel targets that cause
      tumor cells to become chemoresistant. STUDY DESIGN: RHGP was used to identify and
      validate genetic changes that cause chemoresistance of tumor cells to Rapamycin.
      RESULTS: A series of targets was identified that allowed tumor cells to survive
      treatment with Rapamycin. We validated these targets and focused on Annexin A13,
      a target where decreased expression caused tumor cell insensitivity to Rapamycin.
      Ectopic overexpression of Annexin A13 was likewise sufficient to sensitize
      malignant breast cancer cells to treatment with Rapamycin. CONCLUSION: These
      findings expand our knowledge of mechanisms that allow tumor cell drug resistance
      and demonstrate the power of RHGP to identify novel targets and mechanisms.

PMID- 20701075
TI  - Immunohistochemical expression of CD3, CD20, CD45, CD68 and bcl-2 in oral
      squamous cell carcinoma.
AB  - OBJECTIVE: To study the main processes involved in oral squamous cell carcinoma
      (OSCC): apoptosis and inflammation. STUDY DESIGN: The immunohistochemical
      expression of bcl-2, CD3, CD20, CD45 and CD68 were studied by standard linked
      streptavidin-biotin horseradish peroxidase technique in 21 paraffin-embedded OSCC
      specimens in order to establish their possible correlation with the degree of
      tumoral differentiation. RESULTS: A trend was observed for the association of
      inflammatory infiltrate with the degree of tumor differentiation: well and
      moderately differentiated tumors tend to be associated to a dense inflammatory
      infiltrate (57.9% of cases), while poorly differentiated cancers seem to be
      associated to a low inflammatory infiltrate in 85.7% of cases. The most expressed
      molecule was CD68, followed by CD45, CD20 and CD3. Bcl-2 was low or moderately
      expressed, and immunostaining was more diffuse in moderately or poorly
      differentiated oral cancers. CONCLUSION: Inflammatory infiltrate and the degree
      of OSCC differentiation may be linked, but the specific role still remains
      unclear.

PMID- 20701076
TI  - EGFR (HER) family protein expression and cytogenetics in 219 squamous cell
      carcinomas of the upper respiratory tract: ERBB2 overexpression independent
      prediction of poor prognosis.
AB  - OBJECTIVE: To retrospectively evaluate the prognostic impact of gene status and
      protein expression of receptor tyrosine kinases of the HER (human epidermal
      growth factor receptor related) family in relation to established
      clinicopathologic parameters in squamous cell carcinomas of the upper respiratory
      tract. STUDY DESIGN: Immunohistochemistry and fluorescence in situ hybridization
      for HER1-4 and the proliferation marker Ki-67 was performed in 219 cases of head
      and neck squamous cell carcinomas and related to long-term clinical follow-up.
      Additionally, the prognostic impact of chromosomal instability was analyzed.
      RESULTS: High expression of HER1 and HER2 was present in 49.4% and 6.6% of
      tumors, respectively. Expression of HER3 and HER4 appeared negative or
      inconspicuous. A gene amplification of HER1 occurred in 5.2% of tumors, whereas
      none of the tumors showed an amplification of HER2-4 loci. In univariate overall
      survival analysis a negative prognostic impact could be demonstrated for high
      expression of HER2 (p < 0.01), advanced local tumor growth (p < 0.01), lymph node
      metastasis (p < 0.01), presence of residual tumor after surgical therapy (p <
      0.01), high proliferative activity (Ki-67; p = 0.02) and high chromosomal
      instability (p = 0.01). According to the multivariate analysis, the strongest
      negative predictors of survival were advanced tumor growth (p < 0.01), presence
      of residual tumor (p < 0.01), high expression of HER2 (p < 0.01) and chromosomal
      instability (p = 0.03). CONCLUSION: Overexpression of HER2 and presence of
      chromosomal instability harbor an additional prognostic impact on disease
      specific survival and prove to be independent negative prognostic factors in head
      and neck squamous cell carcinomas.

PMID- 20701077
TI  - Comparison of the desmoplastic reaction and invading ability in invasive ductal
      carcinoma of the breast and prostatic adenocarcinoma based on the expression of
      heat shock protein 47 and fascin.
AB  - OBJECTIVE: To investigate the diversity within invasive ductal carcinoma (IDC)
      and prostatic adenocarcinoma (PCa) by evaluating immunohistochemical expression
      of heat shock protein 47 (HSP47) and fascin, the molecules that are related to
      desmoplasia and invasion, and analyze its correlation with clinicopathologic
      parameters. STUDY DESIGN: HSP47 and fascin immunoreactivity (IR) was evaluated in
      49 mastectomies diagnosed as IDC and 57 radical prostatectomies diagnosed as PCa.
      IR was evaluated as: 0: < 5%, 1+: 5-25%, 2+: 25-50%, 3+: > 50%. RESULTS: HSP47
      and fascin were localized to cytoplasm, and HSP47 and fascin IR were higher in
      IDC and PCa than benign groups (p < 0.05). HSP47 IR in neoplastic cells was 42.1%
      and 28.6%, in stroma was 81.6% and 15.8% in IDC and PCa, respectively; fascin IR
      in neoplastic cells was 65.3% in IDC and 15.8% in PCa. Fascin expression
      correlated with estrogen receptor and progesterone receptor negativity, tumor
      size and stage in IDC and surgical margin status in PCa. HSP47 expression
      correlated bilaterality in PCa. HSP47 positively correlated with survival in IDC.
      CONCLUSION: HSP47 and fascin expression may play role in the pathogenesis of IDC
      and PCa because their expression is significantly higher in IDC and PCa than
      their normal counterpart. Although there is no relationship with recurrence or
      metastatic status, fascin overexpression correlated with tumor size, which may
      prompt its use as a prognostic factor in IDC.

PMID- 20701078
TI  - Regression analysis of the initial karyometric data on tumor cells in ductal
      carcinoma and fibroadenoma of the mammary gland.
AB  - OBJECTIVE: To reveal the differences in the parameters of the second order
      regression curve with a cluster of experimental points on scattergrams showing
      the dependence of the perimeter on the area of tumor cell nuclei between ductal
      carcinoma and fibroadenoma of the mammary gland. STUDY DESIGN: Punctate smears
      taken from patients with ductal carcinoma and fibroadenoma of the mammary gland
      with coincident histologic and cytologic conclusion were studied and selected.
      Karyometry of tumor cells was performed with the help of a semiautomatic computer
      analyzer of digital images. RESULTS: It has been shown that the cluster of
      experimental points on scattergrams showing the dependence of the perimeter on
      the area of tumor cell nuclei can be well described by a second order regression
      curve, which is a parabola. The differences in parabola parameters (coefficients
      of the parabola equation) characterizing the population of tumor cells in ductal
      carcinoma and fibroadenoma of the mammary gland were revealed. Boundary values of
      these parameters in the groups of comparison were ascertained. CONCLUSION:
      Parameters of the regression curve to a cluster of experimental points on
      scattergrams showing the dependence of the perimeter on the area of tumor cell
      nuclei can be used as an additional diagnostic criterion for breast cancer.

PMID- 20701079
TI  - Morphometric analysis of dysplastic nodules in hepatitis C virus-related liver
      cirrhosis: comparison with cirrhotic and large regenerative nodules.
AB  - OBJECTIVE: To apply a computerized morphometric model to evaluate and quantify
      the morphologic features, including hepatic progenitor cells, in large
      regenerative nodules (LRN) and high grade dysplastic nodules (DN) in hepatitis C
      virus (HCV)-related cirrhosis. STUDY DESIGN: Thirty-two cirrhotic nodules; 10
      LRN; and 8 DN were identified in cirrhotic livers with HCV-related cirrhosis
      removed at transplantation. All specimens were stained for routine diagnosis with
      hematoxylin-eosin and immunohistochemically for CD31, CD34, cytokeratin 7 (CK7)
      and reticulin. We determined by a computerized morphometric model on hematoxylin
      eosin slices the volume fractions occupied by hepatocyte nuclei and cytoplasm,
      sinusoids, portal triads, fibrosis and centrilobular veins. We also investigated
      volume fraction of hepatocytes expressing CK7, and volume fractions of capillary
      units and of sinusoid capillarization expressing CD31 and CD34, respectively, and
      surface fraction of reticulin. RESULTS: Compared to LRN, DN showed higher volume
      fraction of hepatocyte nuclei, higher number of hepatocytes in unit volume,
      higher nuclear/cytoplasmic ratio, higher volume fractions of capillarized
      sinusoids, capillary units and CK7 positive hepatocytes and lower mean hepatocyte
      volume and surface reticulin fraction. CONCLUSION: Our morphometric model is an
      objective method of quantification of the morphologic changes of LRN and DN,
      including the hepatic progenitor compartment.

PMID- 20701080
TI  - Role of computerized morphometric analysis in the diagnosis of Hirschsprung's
      disease.

PMID- 20701081
TI  - Processing the entire serous effusion: advantages with the 3-dimensional
      filtration unit.

PMID- 20701082
TI  - Correlation of centrosomal aberrations with cell differentiation and DNA ploidy
      in prostate cancer.
AB  - OBJECTIVE: To analyze the centrosomal abnormalities in correlation with DNA
      ploidy and clinicopathologic data in prostate cancer. STUDY DESIGN: Formalin
      fixed, paraffin-embedded material from 63 prostate cancers (PCa) and 10 normal
      control cases were studied. Centrosomal features (number, area and shape) were
      assessed by immunohistochemistry with a gamma-tubulin monoclonal antibody. For
      each case centrosomal features were assessed in 100 cells, and the mean and
      median value was calculated. Statistical analysis was done by Student's t test,
      Mann-Whitney U test and multivariate analysis. The colocalization of gamma
      tubulin and pericentrin at the centrosome was proven by double immunofluorescence
      staining. The DNA ploidy status was analyzed on Feulgen-stained, disintegrated
      paraffin sections using the OPTIMAS-based work station (Media Cybernetics, Silver
      Spring, Maryland, U.S.A.). RESULTS: PCa cells showed centrosomal aberrations when
      compared to normal tissue. Poorly differentiated PCa showed more centrosomal
      abnormalities than well differentiated PCa (p < 0.05). Twenty-seven percent PCa
      were DNA nondiploid and 73% PCa were DNA diploid, respectively, just as all
      control specimens. DNA nondiploid status correlates with centrosomal
      abnormalities (p < 0.05). pT4 tumors showed significantly more centrosomes than
      pT2 and pT3 tumors (p < 0.05). CONCLUSION: Changes in centrosome features
      indicate disturbed centrosome function and are significantly correlated with loss
      of differentiation in PCa. This is the first image analysis study of centrosome
      features in PCa, confirming that centrosome defects are involved in the
      acquisition of chromosomal aberrations in PCa.

PMID- 20701083
TI  - A study of bone marrow neoangiogenesis in chronic lymphocytic leukemia patients.
AB  - OBJECTIVE: To use a purely geometric data-unravelling method to identify, without
      a priori, direct links of neoangiogenesis with known clinicobiologic variables in
      23 untreated chronic lymphocytic leukemia (CLL) patients at the time of marrow
      sampling. STUDY DESIGN: We measured neovascular surface density (CD34 endothelial
      marker) in the 10 most labeled fields (hVA), cellularity (CA) and the percentage
      of avascular fields (AVF) in bone marrow biopsy specimens from 34 patients with
      CLL. Vascular endothelial growth factor (VEGF) was assayed in thawed serum
      samples from 8 of the 23 untreated patients (12 Rai stage 0, 6 Rai stage I-II, 5
      Binet stage B-C). RESULTS: Neoangiogenesis hVA was lower in the 12 stage O
      patients (p < 0.039) and in the 6 patients with nodular interstitial mixed
      infiltration (p = 0.058). The link between hVA and serum VEGF (sVEGF) was
      negative in 8 patients (R = -0.49, -0.70 for a given age). Age was linked to
      moderate interstitial infiltration (p < 0.02), AVF (R = 0.37) and lower sVEGF
      levels (R = -0.676). The blood platelet count showed numerous correlations,
      including links with AVF (R = 0.40), low hVA (R = -0.38), female sex (p = 0.068),
      absence of splenomegaly (p < 0.001), mixed-type infiltration (p < 0.01) and sVEGF
      (R = 0.38, 0.61 for a given age). CONCLUSION: The links revealed by the
      iconography of correlations were described statistically. Surprisingly, negative
      links of hVA with the sVEGF level, 2 known prognostic factors, on the one hand,
      and with the blood platelet count, on the other hand, were found. The direct link
      between disease progression and the amount of avascular hematopoietic tissue
      (NS), not previously described, will require further study. Age should be taken
      into account.

PMID- 20701084
TI  - BRCA1 expression in triple negative sporadic breast cancers.
AB  - OBJECTIVE: To study how to identify patients with "triple negative" sporadic
      breast cancers (BCs) having BRCA1 silenced or down-regulated due to epigenetic
      BRCA1 inactivation. STUDY DESIGN: We selected, from our database, patients
      diagnosed with BC between 1995 and 2001 with tumors exhibiting the "triple
      negative" phenotype. "Triple positive" tumors were used as controls. BRCA1
      protein expression was determined by immunohistochemistry. Methylation specific
      polymerase chain reaction (PCR) and bisulfite sequencing on genomic DNA were used
      to assess BRCA1 promoter methylation. BRCA1 m-RNA expression analysis was
      conducted by real-time PCR. RESULTS: Forty-four triple negative and 68 controls
      (triple positive) were eligible for our analysis. BRCA1 promoter methylation was
      present in 31.8% of triple negative and in 20.6% of triple positive cases. BRCA1
      was inactivated (absent BRCA1 m-RNA expression and lack of BRCA1 protein) in
      21.4% of tumors with BRCA1 promoter methylation, as compared with 6% of non
      methylated ones (p = 0.0453). CONCLUSION: BRCA1 inactivation due to promoter
      methylation could play an important role in some sporadic BC cases. Patients with
      this signature could represent the basis for prospective studies aiming to
      compare clinical response to different drugs.

PMID- 20701085
TI  - Morphologic characterization of cell neighborhoods in neoplastic and
      preneoplastic epithelium.
AB  - OBJECTIVE: To explore tissue organization based on the geometry of cell
      neighborhoods in histologic preparations. STUDY DESIGN: Local complexity of solid
      tissues was measured in images of discrete tissue compartments. Exclusive areas
      associated with cell nuclei (v-cells) were computed using a watershed transform
      of the nuclear staining intensity. Mathematical morphology was used to define
      neighborhood membership, distances and identify complete nested neighborhoods.
      Neighborhood complexity was estimated as the scaling of the number of neighbors
      relative to reference v-cells. RESULTS: The methodology applied to hematoxylin
      eosin-stained sections from normal, dysplastic and neoplastic oral epithelium
      revealed that the scaling exponent, over a finite range of neighborhood levels,
      is nonunique and fractional. While scaling values overlapped across classes, the
      average was marginally higher in neoplastic than in dysplastic and normal
      epithelia. The best classificatory power of the exponent was 58% correct
      classification into 3 diagnostic classes (11 levels) and 83% between dysplastic
      and neoplastic classes (13 levels). CONCLUSION: V-cell architecture retains
      features of the original tissue classes and demonstrates an increase in tissue
      disorder in neoplasia. This methodology seems suitable for extracting information
      from tissues where identification of cell boundaries (and therefore segmentation
      into individual cells) is unfeasible.

PMID- 20701086
TI  - Clinical significance of intratumoral CD8+ regulatory T cells in prostate
      carcinoma.
AB  - OBJECTIVE: To explore Foxp3, a member of the forkhead box family of transcription
      factors, which is a major gene for regulatory T (Treg) cell development of
      CD4+CD25+ or CD8+CD25+ phenotype. STUDY DESIGN: We constructed tissue microarrays
      from 82 patients after radical prostatectomy (RP). Three cores of neoplastic
      tissue and 3 from normal/inflammatory tissue were taken. Sections were
      immunostained for Foxp3 and CD8. Numbers of Foxp3 and CD8 positive cells were
      counted. Serum prostate-specific antigen levels before and after RP, Gleason
      score (GS), surgical margin status and pathologic stage were available. RESULTS:
      Among 82 patients aged 55-76 years (mean 66.1, SD +/- 5.8), 64 (78%) were staged
      pT2 and 18 (22%) pT3. Twenty-nine patients (35%) had positive margins, 24 (29%)
      increasing prostate-specific antigen levels (biochemical relapse) 6 months to 2
      years (SD +/- 24.8 months) after RP. GS was distributed as follows: 41 (50%)
      patients with GS 6 (3+3), 34 (41%) with GS 7 [19 (3+4) and 15 (4+3)], 7 (9%) with
      GS > or = 8. In tumor cores, Foxp3 and CD8 counts correlated (p = 0.012). Foxp3
      counts also correlated with biochemical relapse (p = 0.04). CONCLUSION: Treg
      cells were more common in cancer than in benign prostatic tissue. There are links
      between Foxp3 and CD8+ cells and between Foxp3 positive cells and biochemical
      relapse. Patients with prostate cancer show an immunosuppressive regulatory
      profile, including nonresponsive Tregs. It would be important to find mechanisms
      to target these cells for successful immunotherapy.

PMID- 20701087
TI  - ImmunoCyt and cytokeratin 20 immunocytochemistry as adjunct markers for urine
      cytologic detection of bladder cancer: a prospective study.
AB  - OBJECTIVE: To determine whether ImmunoCyt (uCyt+) immunofluorescence and
      cytokeratin 20 (CK20) immunocytochemistry add additional diagnostic value in the
      detection of urothelial carcinoma (UC) in samples of urine liquid-based cytology
      (LBC). STUDY DESIGN: We prospectively collected voided urine samples from a total
      of 169 in-house patients with a variety of urologic conditions. Voided urine
      samples from 22 healthy individuals who came to the clinic as part of a routine
      annual physical examination were also collected as negative controls. Urine LBC,
      uCyt+ immunofluorescence and CK20 immunocytochemistry were performed on the
      specimen, and all 3 tests were evaluated independently in a blinded fashion.
      Cystoscopy with histologic diagnosis was used as the gold standard for diagnosis.
      RESULTS: Of 169 inpatients, 135 cases had histologic diagnoses, including 93
      cases of UC with primary tumors in 68 and recurrent tumors in 25, 26 cases of
      other urologic malignancies and 16 cases of benign urologic lesions. Comparing to
      LBC, both uCyt+ and CK20 had a significant increase in the sensitivity of
      detecting UC (from 49.4% for cytology to 81.6% and 77.0% for uCyt+ and CK20,
      respectively, p < 0.0001 for both by chi2 test). The specificity, in contrast,
      did not show significant change (from 91.1% for LBC, to 86.7% for uCyt+ and 91.1%
      for CK20, p > 0.05). CONCLUSION: Both uCyt+ and CK20 performed on LBC samples
      showed an improvement in the sensitivity of cytology in detecting UC, especially
      for low grade UC, without a significant decrease in specificity. These tests
      provide useful adjunct markers for cytologic detection of UC.

PMID- 20701088
TI  - Spindle epithelial tumor with thymuslike differentiation in a 2-year-old boy: a
      case report.
AB  - BACKGROUND: The spindle epithelial tumor with thymuslike differentiation (SETTLE)
      is a rare thyroid tumor believed to be derived from ectopic thymus tissue or the
      embryonic remnants of branchial pouches, which displays primitive thymic
      differentiation. Histologic observation of spindle cells may lead to confusion
      with other tumors the development and prognosis of which are very different.
      Differential diagnosis using histochemical markers is essential since although
      there is a tendency to develop blood-borne metastases, tumor growth is slow and
      the survival rate in patients followed up is as high as 70%. It mainly affects
      children and young adults (mean age 15), although cases have been reported in
      patients ranging from 2 to 59. CASE: A 2-year-old boy presented with a tumor on
      the anteroinferior aspect of the neck, which had been growing since birth,
      suggesting a congenital origin. Histologic examination showed spindle cell
      nodules separated by fibrous bands containing mucous glands and cysts filled with
      mucoid material. Immunohistochemical markers revealed primitive differentiation;
      tumor cells stained positive for cytokeratin and vimentin but negative for
      markers indicative of greater differentiation, such as calcitonin, chromogranin,
      calretinin, synaptophysin and S-100 protein. CONCLUSION: This is the first
      reported case of SETTLE in the youngest patient which had been growing since
      birth.

PMID- 20701089
TI  - Electron microscopy: the gold standard in the differential diagnosis of
      chromophobe renal cell carcinoma and oncocytoma.

PMID- 20701090
TI  - Discriminant analysis.
AB  - OBJECTIVE: To present a fully worked numerical example for the derivation of a
      discriminant function in order to provide insight into the processing steps and
      origin of the function coefficients. STUDY DESIGN: The example begins with the
      reduction of a set of raw data to the values needed to calculate the
      variance/covariance matrix. Next the inversion of the covariance matrix by
      pivotal condensation is carried through. This is followed by the calculation of
      the coefficients. All calculations are carried out on a simple hand calculator.
      RESULTS: While discriminant analysis is routinely and widely used in the analysis
      of karyometric data, the process of deriving the discriminant function and its
      coefficients has not been demonstrated in detail, by a numerical example, in over
      50 years. CONCLUSION: It is clearly not practical to conduct, by hand, a
      discriminant analysis on data sets as commonly encountered in karyometry.
      However, the use of a computer algorithm without a full understanding of the
      processing steps has always been deeply unsatisfactory. This tutorial article
      should remedy that situation.

PMID- 20701091
TI  - Quantitative morphometry by image analysis of normal, hyperplastic and cancerous
      ductal breasts.
AB  - OBJECTIVE: To analyze a number of quantitative variables in ductal epithelial
      breast proliferations and test them against diagnoses established by standard
      histologic and cytologic criteria in order to determine which variables are
      useful in discriminating between histologic diagnoses. STUDY DESIGN: A method was
      developed for the semiautomatic segmentation and quantitative analysis of breast
      ductal proliferations using image analysis. This permitted duct profiles and
      intraductal epithelial proliferations to be analyzed by computer, with
      calculation of a total of 17 variables--for example, nuclear/cytoplasmic ratio,
      nuclear circularity, average internuclear distance and lumen area. Four groups
      were analyzed employing a total of 80 cases with diagnoses established by
      standard histologic criteria, including normal breast duct (DN = 19 cases),
      ductal hyperplasia without atypia (DH = 21 cases), ductal carcinoma in situ (DCIS
      = 20 cases) and invasive ductal carcinoma (INV = 20 cases). RESULTS: Of the 17
      quantitative variables tested in this study, 15 showed statistically significant
      differences in values between DH and DCIS (p < 0.05), and 7 showed statistically
      significant differences between DN and DH (p < 0.05). CONCLUSION: By quantitative
      morphometric analysis of selected variables, a significant statistical
      distinction can be made between diagnostic groups, paving the way for automatic
      computerized image recognition for differential diagnosis.

PMID- 20701092
TI  - A pilot study investigating the minimum requirements necessary for grading
      astrocytomas remotely.
AB  - OBJECTIVE: To investigate the minimum requirements necessary for remote grading
      astrocytomas in terms of selected static images and descriptive histologic
      characteristics. STUDY DESIGN: A histopathologist examined 106 formalin-fixed,
      paraffin-embedded tissue samples of low- and high-grade astrocytomas.
      Interobserver-checked cases were reviewed under a microscope to estimate the
      accuracy of the conventional glass slide diagnoses. Then cases based on 5 static
      digitized images from each patient were diagnosed. Next, the grade of each tumor
      was assessed based on the set of 5 images and the World Health Organization (WHO)
      description of 8 histologic characteristics defined as crucial in grading
      astrocytomas. Finally, an evaluation was made using a custom-designed decision
      support system. RESULTS: Conventional glass slide diagnosis was 93.9%. Diagnosis
      based only on the set of 5 images dropped to 81.6%. Diagnosis based on the set of
      5 images and the WHO characteristics boosted accuracy to 88.8%. Accuracy improved
      to 91.8% with the addition of the decision support system. CONCLUSION: Our
      findings suggest that a telepathology system might be valuable for accurate grade
      diagnosis of astrocytomas-providing a means for avoiding diagnostic errors
      without blocks or slides having to leave the department. This could significantly
      reduce the overall time and cost of diagnosis.

PMID- 20701093
TI  - Lymphatic vessel density in the normal-looking columnar epithelium adjacent to
      and distant from prostatic intraepithelial neoplasia and prostate cancer assessed
      in whole-mount sections.
AB  - OBJECTIVE: To evaluate the lymphatic vessel density (LVD) in radical
      prostatectomy using the lymphatic marker D2-40 and analyze if LVD is variable
      within the whole-mounting samples of prostatectomy in different areas of
      carcinoma, high- and low-grade prostatic intraepithelial neoplasia and nodular
      hyperplasia. STUDY DESIGN: From each of the 4 cases used for this study, we
      divided the whole-mount slides into 12 regions. Forty-eight regions were examined
      immunohistochemically. The LVD of D2-40 positive endothelial cells into the
      radical prostatectomy was estimated by drawing the areas of interest (lymphatic
      endothelium) dispersed along the prostate zone to facilitate the counting of the
      positive cells within prostate areas (normal-looking cells, hyperplastic cells,
      intraepithelial neoplasia and invasive neoplasia). The results were expressed as
      number of cells per area. RESULTS: LVD counting for nodular hyperplasia of
      prostate, low-grade prostatic intraepithelial neoplasia, high-grade prostatic
      intraepithelial neoplasia and prostate carcinoma was 1.29, 1.20, 1.26 and 1.13,
      respectively. The statistical analysis (p = 0.265) showed an absence of
      significant differences of LVD analysis among the lesions. CONCLUSIONS: LVD in
      prostatic cancer does not appear importantly enhanced around tumoral stroma. The
      lymphatic vessel distribution was quite similar around malignant and nonmalignant
      areas within the same prostatectomy samples.

PMID- 20701094
TI  - Glomerular retrieval by cell block preparation of preservative fluid: an adjunct
      to biopsy diagnosis.
AB  - OBJECTIVE: To investigate the possibility of glomerular retrieval from formalin
      left in biopsy vials and to evaluate its diagnostic value and accuracy. STUDY
      DESIGN: Cell blocks were prepared from 94 consecutive formalin vials left after
      processing of renal biopsies from 93 patients, including 25 transplant patients.
      The prepared cell blocks were processed with routine biopsies and evaluated
      separately, and the results compared. RESULTS: Of the 94 samples, 29 (23
      nontransplant patients and 6 allograft recipients) showed the presence of
      glomeruli in cell blocks, with an average of 1.7 glomeruli per cell block. In
      nonallograft native renal biopsies, the histologic diagnosis of glomerular
      morphology in cell blocks correlated with routine biopsy in 18 of 22 cases. The
      least retrieval was seen in crescentic glomerulonephritis, diabetic
      glomerulosclerosis and diffuse global glomerulosclerosis, possibly due either to
      the tight adherence of the glomerular tuft to the crescent or to fibrosis. All 6
      samples from transplant recipients showed normal glomeruli in routine histology
      and in cell block preparations. CONCLUSION: Cell blocks from discarded formalin
      may be a useful adjunct to routine histopathology for the diagnosis of glomerular
      disease in centers where inadequacy of renal biopsy is frequently reported.

PMID- 20701095
TI  - Salivary gland tumors: immunohistochemical study of EGF, EGFR, ErbB-2, FAS and Ki
      67.
AB  - OBJECTIVE: To analyze the expression of ErbB-1 (Her-1 or EGFR), ErbB-2 (Her-2 or
      neu), ErbB-3 (Her-3) and ErbB-4 (Her-4) and their correlation in 3 different
      types of salivary gland tumors. STUDY DESIGN: Immunohistochemical expression of
      epidermal growth factor (EGF), EGFR, ErbB-2, fatty acid synthase (FAS) and Ki-67
      were analyzed in 41 pleomorphic adenoma (PA), in 30 mucoepidermoid carcinoma
      (MEC) and in 30 adenoid cystic carcinoma (ACC) and correlated with their
      histologic patterns. RESULTS: EGF was more common in MEC and PA, but MEC had a
      higher percentage of strongly positive cases. EGFRc and EGFRm were both more
      frequent in MEC and ACC. Higher scores of ErbB-2c were observed in PA, followed
      by MEC and ACC. In contrast, higher scores of ErbB-2m were more common in MEC as
      compared to ACC and PA. FAS was most commonly found in PA and MEC. Moreover, MEC
      showed the highest percentage of strongly positive cases. Ki-67 was higher in MEC
      and ACC than in PA. From a correlation of immunomarkers with the histologic
      patterns, it was observed that cribriform ACC presented more expression of EGFR
      and high grade MEC showed a higher percentage of ErbB-2, FAS and Ki-67.
      CONCLUSION: EGF, EGFR, ErbB-2 and FAS were commonly found and seem to be
      important in the tumorigenesis of salivary gland tumors, particularly in
      percentage of strongly positive cases. Ki-67 was higher in MEC and ACC than in
      PA. From a correlation of immunomarkers with the histologic patterns, it was
      observed that cribriform ACC presented more expression of EGFR and high grade MEC
      showed a higher percentage of ErbB-2, FAS and Ki-67. CONCLUSION: EGF, EGFR, ErbB
      2 and FAS were commonly found and seem to be important in the tumorigenesis of
      salivary gland tumors, particularly in MEC. (Anal Quant Cytol Histol 2009;31:280
      287)

PMID- 20701096
TI  - Quantification of transforming growth factor beta 1 levels in metastatic axillary
      lymph node tissue extracts from breast cancer patients: a new specimen source.
AB  - OBJECTIVE: To use cytoplasmic tissue extract as a new specimen source to quantify
      transforming growth factor beta 1 (TGFbeta1) protein in metastatic axillary lymph
      node tissue (ALNT) of breast cancer (BC) patients and to confirm the feasibility
      of this approach in a prospective pilot study on a subgroup of patients with
      invasive BC. STUDY DESIGN: The 6 selected malignant and autologous nonmalignant
      pairs of ALNT were fractionated, under special preanalytical,
      nonaggressive/nondenaturing conditions, to obtain respective cytoplasmic extracts
      for TGFbeta1 detection by the Quantikine (R&D Systems Inc., Minneapolis,
      Minnesota, U.S.A.) enzyme-linked immunosorbent assay kit. RESULTS: The data
      indicated a highly significant (r = 0.973054) positive linear correlation between
      the TGFbeta1 concentration and total protein concentration in cytoplasmic extract
      of metastatic ALNT. The subsequent patients' pilot study, performed strictly
      before any clinicopathologic factors were accessible, revealed significantly (p <
      0.01) elevated TGFbeta1 in malignant ALNT (median value: 1.05 ng/mg protein,
      range: 0.67-3.6 ng/mg protein, n = 6) vs. autologous nonmalignant ALNT controls
      (median value: 0.48 ng/mg protein, range: 0.29-0.90 ng/mg protein, n = 6). This
      elevation was correlated with the number of metastatic axillary lymph nodes with
      respect to the total and was consistent with an increase in size of tumor
      deposits in axillary lymph nodes. CONCLUSION: Our data provide for the first time
      suggestive evidence that the TGFbeta1 level in cytoplasmic extracts of metastatic
      ALNTs may be a promising biomarker of invasiveness for BC patients. Confirmatory,
      large-scale studies are needed to evaluate possible implications of this putative
      biomarker in BC diagnosis and treatment.

PMID- 20701097
TI  - Study of diagnostic and prognostic parameters (including flow cytometry) in
      chronic lymphoproliferative disorders: the Indian perspective.
AB  - OBJECTIVE: To assess for chronic lymphoproliferative disorders (CLPD) using
      several diagnostic and prognostic parameters, including cell morphology,
      immunologic markers and molecular and cytogenetic investigations, some of which
      had not been used in the assessment of patients in India. STUDY DESIGN: This
      prospective study involved the analysis of peripheral blood and bone marrow (BM)
      aspirate morphology, BM infiltration pattern and lymphoid cell flow cytometry
      (FCM) in patients with CLPDs. These findings were compared with other disease
      parameters. RESULTS: Chronic lymphocytic leukemia (CLL) and hairy cell leukemia
      (HCL) were the most commonly encountered CLPDs among 91 CLPD patients. Seventy
      cases were diagnosed as CLL, 14 as HCL and 7 as miscellaneous. Sixty-nine CLL
      cases showed typical CLL immunophenotype. Thirteen HCL cases revealed typical HCL
      immunophenotype. Rai and Binet staging systems were applied, and the correlation
      of various stages with other prognostic parameters like BM trephine biopsy
      patterns, CD38 positivity, serum lactic dehydrogenase level, lymphocyte doubling
      time and Coomb's test was analyzed. BM infiltration pattern showed significant
      statistical correlation with staging systems. CONCLUSION: The advantage of FCM is
      being realized increasingly in India, therefore this study is likely to serve as
      a baseline data in our set-up.

PMID- 20701098
TI  - Color deconvolution for the analysis of tissue microarrays.
AB  - OBJECTIVE: To analyze tissue microarrays (TMAs) using color deconvolution, a
      method for separating component dyes in digital images, and compare the results
      to observer scoring. STUDY DESIGN: TMAs were constructed from tissues from 100
      adult autopsies and immunohistochemically stained for connective tissue growth
      factor. A region of interest (ROI) was created for each core image using 3 binary
      masks-tissue area, inclusion area and exclusion area. The diaminobenzidine (DAB)
      and hematoxylin signals were deconvolved, and the DAB signal was measured for
      each ROI. The dorsalis pedis core images were also scored manually. RESULTS:
      Seventeen TMAs were annotated, requiring 532 minutes. Of the 1,683 cores, 296
      (18%) were excluded because they were not suitable for evaluation. A single TMA
      required a mean of 31.3 minutes to evaluate; to annotate a single core took a
      mean of 19 seconds. For the dorsalis pedis, observer score and median DAB
      intensity correlated strongly (Kendall's = 0.71). CONCLUSION: Analysis of TMAs by
      color deconvolution is efficient and highly correlates to observer scoring.

PMID- 20701099
TI  - New parameters of diploid histogram of image DNA cytometry and newly
      characterized types of nucleolar organizer region structures in defining the
      proliferative-kinetic index in chronic leukemic lymphoproliferative disorders.
AB  - OBJECTIVE: To introduce new parameters of diploid histogram of image DNA
      cytometry and new types of silver-stained nucleolar organizer regions (AgNORs)
      and to validate resulting proliferative-kinetic index (PKI) in a prognostic study
      of patients with chronic leukemic lymphoproliferative disorders (CLLPD). STUDY
      DESIGN: A total of 413 smears of from various tumor mass compartments-bone
      marrow, peripheral blood and lymph node-were analyzed in CLLPD as a whole, as
      well as separately in the B-chronic lymphocytic leukemia with variants (B-CLL+V).
      The analysis of the diploid histogram included percentage of cells at the peak of
      the DNA histogram and percentage of cells with lower and higher contents of DNA
      than cells at the peak. The new types of AgNORs were described as homogeneous,
      inhomogeneous and annular. RESULTS: The newly introduced parameters of DNA and
      AgNOR are significant predictors of survival. Based on the most representative
      AgNOR and DNA characteristics related to survival, the PKI score was calculated.
      The CLLPD and B-CLL+V patients had a statistically significantly better prognosis
      when PKI was < 4. CONCLUSION: PKIs have confirmed the hypothesis that different
      prognostic subgroups could be identified within the homogeneous groups of
      neoplasms with relatively low malignancy (CLLPD and B-CLL+V).

PMID- 20701100
TI  - Expression of beta-catenin in human tooth germ.
AB  - OBJECTIVE: To evaluate beta-catenin expression in human tooth germ development.
      STUDY DESIGN: Specimens of 7 human fetuses aged between the ninth and sixteenth
      week were examined for beta-catenin expression by immunohistochemistry. RESULTS:
      In the bud stage, we observed catenin membranous positivity for all primitive
      dental lamina and dental ridge cells, cytoplasmic positivity for tooth bud and
      intense nuclear positivity for early-condensed dental mesenchyme. The cap stage
      was marked by intense cytoplasmic and nuclear positivity in the outer and inner
      enamel epithelium and the dental papilla and by moderate cytoplasmic positivity
      in the enamel knot. In the early bell stage, we noted strong cytoplasmic and
      nuclear staining in the inner and outer enamel epithelium, only moderate
      membranous and cytoplasmic staining in the stellate reticulum, a high percentage
      of intense nuclear positivity in the dental papilla and strong focal nuclear and
      cytoplasmic positivity in the dental sac. CONCLUSION: All areas with close
      contact between epithelial structures and ectomesenchymal cells showed increased
      expression of delocalized cytoplasmic and nuclear beta-catenin. Nuclear
      localization, tissue expression pattern and timing suggest a pivotal role for
      beta-catenin in the transcriptional activation of genes probably involved in the
      mesenchyme-epithelial interactions on which human tooth development is based.

PMID- 20701101
TI  - DNA ploidy, E-cadherin, beta-catenin expression and their clinicopathologic
      significance in imprints of non-small cell lung cancer.
AB  - OBJECTIVE: To evaluate, in imprints of resected non-small cell lung cancers
      (NSCLCs), the relationship between DNA ploidy and E-cadherin/beta-catenin
      expression with classical prognostic factors. STUDY DESIGN: A total of 45
      patients (28 squamous cell carcinomas and 17 adenocarcinomas) who underwent
      surgical treatment for NSCLC were examined with immunocytochemistry for the
      expression of E-cadherin/ beta-catenin imprint smears, which also were stained
      using the Thionin Feulgen procedure in order to evaluate DNA ploidy in the same
      cases. RESULTS: Thirty-two (71.1%) of the tumors were classified as aneuploid. E
      cadherin-positive expression was observed in 18 (40%) and p-catenin in 21 (46.7%)
      of the tumors. We found a significant relationship between DNA ploidy and grade
      (p= 0.005). E-cadherin and beta-catenin expression correlated with grade (p <
      0.0001 for both) and also with nodal status (p = 0.004 and p = 0.017,
      respectively). The mean DNA index was higher for tumors with negative expression
      of E-cadherin/beta-catenin (p = 0.045 and p = 0.025, respectively). CONCLUSION:
      DNA aneuploidy correlates with poor and moderately differentiated tumors. E
      cadherin- and beta-catenin-positive expression is in relation to well
      differentiated carcinomas and nodal metastasis. The relationship between DNA
      ploidy and E-cadherin/beta-catenin needs to be further investigated.

PMID- 20701102
TI  - Ezrin immunoreactivity in renal cell carcinomas.
AB  - OBJECTIVE: To determine ezrin's association with clinicopathologic features and
      to investigate the possible effects of the presence of ezrin on the differential
      diagnosis of subtypes of renal cell carcinoma (RCC). STUDY DESIGN: Ezrin
      reactivity was examined immunohistochemically in tumor tissues obtained from 78
      patients who underwent radical nephrectomy for renal cell carcinoma. Correlation
      between ezrin expression and RCC subtypes was investigated and compared with
      tumor stage, grade and other clinicopathologic parameters. RESULTS: There was no
      correlation between ezrin expression and clinicopathologic features. Furthermore,
      a significant correlation was found between ezrin reactivity and subtypes of RCC
      (p = 0.002). Ezrin reactivity was observed mainly in conventional, papillary and
      mucinous tubular spindle cell carcinoma (MTSCC) subtypes of RCC, while none of
      the chromophobe RCC was positive for ezrin. Sarcomatoid and unclassified subtypes
      of RCC were found to be faint and/or negative for ezrin reactivity. CONCLUSION:
      Investigation of ezrin reactivity may be beneficial as an additional diagnostic
      marker in the differential diagnosis of RCC subtypes. Also, it seems to be useful
      to designate the origin of MTSCC.

PMID- 20701104
TI  - Fractal dimensions of reactive mesothelial cells and malignant cells in ascitic
      fluid cytology.

PMID- 20701103
TI  - Nuclear margin irregularity and cancer: a review.
AB  - Nuclear margin irregularity is an important diagnostic feature of malignant
      cells. The exact cause of nuclear margin irregularity is not fully understood.
      The distortion of the nuclear envelope is probably the major factor in nuclear
      margin irregularity. Multiple proteins on the nuclear envelope, particularly
      nuclear lamin, are responsible for the distortion of the nuclear envelope. The
      extracellular matrix may also indirectly affect the nuclear position and shape by
      the closely connected network of actin-nespirin-SUN-lamin links. The alteration
      of nuclear matrix protein and RET-oncogene expression may play a role in nuclear
      envelope distortion and in margin irregularity. In this review, the probable
      causes and impact of nuclear margin irregularities are discussed.

PMID- 20701105
TI  - Subacute effect of 2,4-dichlorophenoxyacetic acid on rat liver tissue:
      histochemical and immunohistochemical study.

PMID- 20701106
TI  - [False self-possession].

PMID- 20701107
TI  - [Fraudulent studies, unpublished data and their effect on the development of
      guidelines and evidence-based recommendations].
AB  - Publication bias and scientific fraud are major threats to valid guidelines,
      especially guideline recommendations. Both topics have so far not been
      investigated systematically. It is assumed that guideline authors underestimate
      the potential influences on the validity of their recommendations. On the basis
      of questions and the example of depression guidelines the potential influence of
      publication bias will be outlined and discussed. Formal consensus processes which
      are used to phrase and grade recommendations might protect guideline
      recommendations against the influence of publication bias and might thereby imply
      one major difference to systematic reviews. Based on the examples of Werner
      Bezwoda and Scott S. Reuben, who fabricated studies in breast cancer and
      analgesia, it can be estimated that scientific fraud has no or only minimal
      effect on the recommendations given in clinical guidelines. Either the fraudulent
      work is in line with other (true) studies, which consequently leads only to an
      overestimation of the quantity of evidence in the guideline. Or the faked study
      is the only piece of evidence available, which guideline authors would then
      regard as an insufficient basis for a clinical recommendation. Although
      publication bias and scientific fraud had no influence on the example guidelines,
      guideline authors should be aware of this possibility and control this problem by
      systematically reviewing the evidence, critically appraising primary studies, and
      formulating prudent recommendations.

PMID- 20701108
TI  - [Searching clinical trials registries: procedure and documentation].
AB  - The identification of unpublished data is an important component in the
      assessment of drugs for a systematic review. This is why searching in clinical
      trials registries is indispensable. However, this type of search is not regularly
      conducted. At present, clinical trials registries that also contain results data
      are still seldom-used sources, which may be due to a number of reasons. On the
      one hand, there are a large number of clinical trials registries whose quality is
      difficult to judge sometimes; on the other hand, their heterogeneity and partly
      inadequate functionality such as, for example, the lack of export options,
      complicate searches of these sources. The present paper addresses the features of
      searches in clinical trials registries and describes the approach taken by the
      German Institute for Quality and Efficiency in Health Care (IQWiG). Initially, we
      describe the various types of registries and offer assistance with the selection
      of the clinical trials registries to be searched. A further focus lies on the
      description of the search procedure itself, as well as on the selection of the
      relevant registry entries and the documentation of this process in order to
      support those planning their own search in clinical trials registries.

PMID- 20701109
TI  - [Results registries for clinical trials--a milestone on the way to transparency
      in clinical research?].
AB  - Publication bias, i.e., the publication of trial results depending on the nature
      and direction of results, is a significant problem in healthcare, as it leads to
      a biased view of the treatment options available. Furthermore, publication bias
      hampers the adequate planning and conduct of future clinical trials. One proposal
      to reduce publication bias is the registration of trials and trial results.
      Whereas the registration of trials at inception is largely accepted and partly
      established, the registration of trial results is still being intensively
      discussed. Open issues particularly refer to legal obligations in the
      registration of trial results as well as to the nature and extent of their
      presentation. Whilst in the United States a comprehensive legal regulation on
      results registration has already been implemented, compulsory registration in
      Europe is still at a preliminary stage. The present paper describes the status
      quo of results registries, discusses registration requirements, and outlines the
      need to develop methods for the handling of results registries.

PMID- 20701110
TI  - [Statistical methods for detecting and adjusting for publication bias].
AB  - Publication bias in meta-analysis occurs if the probability of publication
      depends on the estimated treatment effect and the precision/size of a study. In
      this article we describe the funnel plot as a graphical method to evaluate the
      presence of publication bias. Furthermore, tests of publication bias based on
      funnel plots are explained, and methods are presented that estimate treatment
      effects adjusted for publication bias. The article closes with a critical
      discussion of the various statistical methods.

PMID- 20701111
TI  - [The relation between publication bias and clinical trials funding].
AB  - Publication bias describes the distortion of data in scientific journals
      resulting from the fact that studies with significant and positive results are
      more likely to be published than studies with negative or insignificant results.
      In studies funded by pharmaceutical companies publication bias has a considerable
      impact. It has been shown that more than half of the studies that are conducted
      as part of the drug approval process will remain unpublished. In addition,
      multiple publications of the same results, the selective use of data and the
      withholding of data relating to adverse drug reactions were also demonstrated. It
      is unclear, however, whether the probability of publication of studies funded by
      pharmaceutical companies is different from those not funded by pharmaceutical
      companies. Also, data vary as to the correlation between the type of funding of
      clinical studies and the length of time to publication. For the benefit of
      patients, everyone involved in clinical studies ought to take responsibility and
      facilitate access to all data.

PMID- 20701112
TI  - [Decisions of the Federal Joint Committee for rejecting work with "weak" or
      failing evidence].
AB  - With the aim to study the level of evidence on which coverage decisions of the
      Federal Joint Committee (G-BA) were made and how the G-BA deals with missing or
      insufficient evidence, we analysed the final reports of coverage decisions after
      benefit assessments (outpatient care) between 1.1.1998 and 31.10.2008. A total of
      36 decisions were analysed. 12 technologies were adopted for provision in
      outpatient care, 22 were excluded and two were suspended of assessment procedure
      until new evidence is provided. The G-BA decided in each case on the basis of the
      best available evidence. In the majority of negative decisions (16 of 22) no
      randomised controlled trials (RCTs) were available, the decision was therefore
      made on the basis of non-randomised studies. Even five of 12 positive decisions
      lacked evidence based on RCTs. In these cases the G-BA acknowledged that the
      evaluation of efficacy in randomised clinical trials was, due to the disease
      characteristic, not feasible. The G-BA uses different ways to deal with missing
      or insufficient evidence. It should be noted that the concept of missing evidence
      in the public is often diffuse and should be better defined.

PMID- 20701113
TI  - [Why it is necessary to improve data quality and data validity by implementing a
      timely and integrated controlling system for BQS-compliant quality assurance].
AB  - Since 2007, all German hospitals are obliged to publish 27 quality indicators in
      their biannual "structured quality reports" as defined by the BQS (= Federal
      Office for Quality Assurance). Thus, hospitals are required to establish a timely
      controlling system for process and outcome quality that goes beyond the mere
      control of documentation rates. The University Medical Center Ulm has implemented
      an IT solution that allows for the continuous and timely evaluation of the
      quality assurance reports of the different modules. By developing an internal
      dialogue with colleagues of all specialties it was possible to optimise adherence
      to documentation and process standards, and to react promptly to deviations in
      outcome quality. This improved the quality of documentation and therefore the
      validity of quality assurance data. It even led to the identification of a
      programme error in the export file of one of the external modules. By cross
      checking quality assurance data and accounting data according to Sect. 21 KHEntG
      (= regulation for DRG case invoicing), it was possible to detect down-coding in
      several cases and therefore increase revenue by correcting the accounting record.
      In current times it should be mandatory for hospitals to establish an internal IT
      supported medical/quantitative control system of BQS data records for external
      quality assurance. Quality and quantity of documentation forms the basis for the
      so-called internal dialogue (standardised review process of substandard quality
      assurance results), and they allow to identify the potentials for improvement in
      the quality of care for our patients.

PMID- 20701114
TI  - [Radicaldebridement and restabilization for the treatment of spinal
      tuberculosis].

PMID- 20701115
TI  - [Therapeutic principle and correlative problem in treating spinal tuberculosis].

PMID- 20701116
TI  - [Surgical treatment of drug-resistant spinal tuberculosis].
AB  - OBJECTIVE: To study the curative effect of surgical treatment of drug-resistant
      spinal tuberculosis. METHODS: From March 2005 and April 2009, the clinical data
      of 60 patients with drug-resistant spinal tuberculosis were retrospectively
      analyzed. Including 36 males and 24 females; aged from 5 to 79 years with an
      average of 47.3 years. Thirty-four patients had neurological deficits, among
      them, 2 cases were grade A, 5 cases were grade B, 13 cases were grade C, 14 cases
      were grade D according to ASIA standard. According to the severity and location
      of the infection, the patients underwent anterior, posterolateral
      costotransversectomy or posterior debridement and bone grafting and internal
      fixation. The antituberculous chemotherapy for a total of 12 to 18 months was
      guided by conventional and genotypic drug susceptibility testing. Tubercular
      relapse, neurological function, spinal fusion were observed by ASIA grade, X-ray
      and CT scan. RESULTS: All cases were followed up from 1 to 5 years with an
      average of 3.1 years. Recurrence was found in 2 cases who were cured after second
      operation. 34 cases with neurological deficits recovered totally or partially. X
      ray or CT films showed spinal fusion in 57 patients. CONCLUSION: The therapeutic
      effect of individuall operative options is good in treating drug-resistant spinal
      tuberculosis after antituberculous chemotherapy based on conventional and
      genotypic drug susceptibility testing.

PMID- 20701117
TI  - [Surgical treatment of thoracic and thoracolumbar spinal tuberculosis].
AB  - OBJECTIVE: To explore the surgical measurements and principles in the treatment
      of thoracic and thoracolumbar spinal tuberculosis. METHODS: From 2001 to 2008,
      232 cases of thoracic or thoracolumbar spinal tuberculosis were treated by
      operations in the study, including 148 males and 84 females with an average age
      of 37.8 years ranging from 20 to 76 years. Preoperative assessment displayed as
      follow: Cobb angles of kyphosis < 30 degrees in 65 cases, 30 degrees to 60
      degrees in 147 cases, > 60 degrees in 20 cases; Frankel B grade in 13 cases, C in
      12 cases, D in 41 cases, E in 166 cases. Among them, 48 cases were performed with
      one-stage transpedicular screw system and anterolateral debridement by single
      incision, 184 cases with one-stage anterior approach (debridement, fusion, and
      plate-screw fixation) routinely. The tissues and liquor puris debrided from focus
      were sent for pathological examination, Bacillus tuberculosis detection and
      culture, and drug sensitivity test. The patients were given anti-tuberculosis
      therapy according the results of drug sensitivity test for 1 to 1.5 years. The
      followed-up included relapse rate, fusion of the bone graft, the status of
      neurological restoring, kyphosis correction etc. RESULTS: All 232 cases recovered
      from perioperation and 230 cases got primary wound healing, only 2 cases
      performed with single incision one-stage posterior instrumentation and
      anterolateral debridement got complications of wound healing problems and the
      sinus formation,which delayed healed by changing dressings. The complications
      included intercostals neuralgia in 135 cases and pneumothorax or hydrothorax in
      13 cases, which needed not special handling. All the patients in this series got
      the followed-up ranging from 1.0 to 4.5 years (means 2.6 years). No recurrence
      within followed-up period and bone union was found in all cases. All 66 cases
      with the neurological deficits recovered partially or totally. Kyphosis
      correction were achieved by 27.5 degrees on average postoperatively and showed a
      mild loss of 4.2 degrees on average during followed-up period. All cases were
      confirmed with Bacillus tuberculosis infection by pathology. Bacillus
      tuberculosis was detected and culture successfully in 107 cases (46.1%), 40
      strains (37.4%) were drug resistant and in which 8 strains (7.5%) were multi-drug
      resistant. CONCLUSION: For the treatment of thoracic and thoracolumbar spinal
      tuberculosis, the best treatment include directional chemotherapy, one-stage
      anterior approach with thorough debridement, auto-rib or Ti-mesh fusion, and
      plate-screw fixation.

PMID- 20701118
TI  - [Clinical study of short-course chemotherapy combined with radical operation in
      retreating spinal tuberculosis].
AB  - OBJECTIVE: To investigate clinical outcome of short-course chemotherapy in
      retreating spinal tuberculosis after radical operation. METHODS: Forty-six
      retreating patients with spinal tuberculosis were included in this series, 29
      males, 17 females with the age from 27 to 61 years (average of 43.7 years). All
      patients were treated with radical operation and short-course anti-tuberculous
      chemotherapy from March 2005 to March 2008. The tuberculous focus located
      thoracic spine in 17 cases, thoracic-lumbar in 13 and lumbosacral vertebrae in 16
      cases. Of them, 5 cases had sinuses of tuberculosis and 7 cases had incomplete
      palsy in lower limbs (Frankel C-D). CT or MRI showed obvious sequestra, cold
      abscess within spinal focus. Surgical procedures including debridement, auto-bone
      grafting, and one-stage internal fixation, was performed at the 4 to 6 weeks
      after chemotherapy. Chemotherapy regimes were 3HRZ/6-9HRE in majority of
      patients. Clinical effect and focus healing were evaluated at follow-up period.
      RESULTS: Tuberculous symptoms and local pain of vertebral volume were obvious in
      all patients before chemotherapy,with average ESR 65.3 mm/h and average CRP 37.4
      mg/L. After 4-6 weeks chemotherapy, tuberculosis symptoms and vertebral pain
      improved in all patients, and the average ESR decreased to 38.3 mm/1h, the
      average CRP decreased to 17.2 mg/L. Two to three months after operation,
      tuberculous symptoms and local pain relived in all patients,ESR and CRP became
      normal in 37 cases. Six to twelve months after operation, bonegraft complex in
      each patient became stable and there were no instrument loosening or deformity
      correction loss. Six patients with incomplete palsy recovered and 1 case improved
      from Frankel C to D grade. Focus healing was achieved in 44 cases (95.7%) after
      short-course chemotherapy (3HRZ/6-9HRE), and there were no resurgence in 2 to 4
      years follow-up period. Drug fast 2 cases for RFP+INH cured at the 15 months
      after chemotherapy. CONCLUSIONS: Removed tubercular focus for the treatment of
      retreating spinal tuberculosis can improve clinical effect and shorten
      chemotherapy course.

PMID- 20701119
TI  - [Internal fixation failure of cervical vertebral tuberculosis with uremia: a case
      report].

PMID- 20701120
TI  - [Analysis of the curative effect of 162 cases of thoracic and lumbar
      tuberculosis].
AB  - OBJECTIVE: To explore the differences between conservative and surgical treatment
      for thoracic and lumbar spine tuberculosis on indications and clinical results.
      METHODS: From May 2000 to June 2008, 162 cases of thoracic spinal tuberculosis
      patients were studied retrospectively, including 89 males and 73 females, aged
      from 4 to 71 years (means 43.6 years). Among them, 38 cases of onset time was
      short, X-ray showed a narrow cone gap and MRI showed vertebral body signal
      changes, the ones who had better general condition were applicated of anti-TB
      drugs [6HREZ (S)/6-9HRE] and traditional Chinese medicine dialectical; 51 cases
      with thick swollen and vertebral body marginal damage but not affect the
      stability of spine, were treated with spinal tuberculosis debridement surgery; 73
      cases with abscess, vertebral destruction of center, spinal instability or spinal
      cord function associated with damage to persons, were treated with surgical
      debridement and interbody bone grafting and fixation. Clinical observation were
      evaluated according to the standard cure for bone tuberculosis. RESULTS: Thirty
      eight cases by conservative treatment, had been cured in 1 to 2 years. Focus of
      infection cleared in 51 cases, 3 cases occurrenced the sinus next to incision, 4
      cases of kyphosis angle (Cobb) lost 5 degrees-10 degrees compared with that
      before treatment (means 4.5 degrees). Seventy-three cases by internal fixation
      obtained neurological deficiency symptoms recovery; 2 occurenced the sinus next
      to the incision, 3 cases appeared subcutaneous emphysema of iliac area and local
      pain, but need no special treatment. A total of 136 patients were followed-up
      from 12 to 60 months with an average of 32.8 months, and had been all clinically
      cured. CONCLUSION: Patients with early detection only on the imaging showing
      vertebral lesions, without obvious sequestrum, abscesses, can be selected for
      conservative anti-tuberculosis treatment. Patients combined with abscess,
      vertebral destruction on light degree and not affected the stability of the
      spine, can be removed by simple surgery to obtain better efficacy. Patients with
      abscesses, sequestrum, spinal vertebral instability leading to heavy damage
      associated with spinal cord or nerve function impairment,will need surgical
      removal of lesions of tuberculosis, give graft and spinal fixation at the same
      time.

PMID- 20701121
TI  - [Effects of Tongmai decoction on the perioperative changes of plasma TNF-alpha
      and IL-6 in patients with femoral fractures].
AB  - OBJECTIVE: To explore the effects of Tongmai decoction on the perioperative
      changes of serum concentrations of tumor necrosis factor alpha (TNF-alpha) and
      interleukin (IL)-6 in patients with femoral fractures, and conform the
      effectiveness of Tongmai decoction on inflammatory factors in patients with
      femoral fractures, providing the theoretical evidence for the clinical use of
      Tongmai decoction. METHODS: From October 2007 to May 2009, 60 patients with
      closed traumatic femoral fractures were selected according to the inclusion
      criterias and exclusion criterias. All the patients were randomly divided into
      three groups (group A, group B and group C). Twenty patients in group A (Tpanax
      Notoginseng pill group), 13 patients were male and 7 patients were female;
      ranging in age from 20 to 45 years, averaged 32.0 years; the disease course
      ranged from 2.0 to 26.0 h, with an average of 9.5 h. Twenty patients in group B
      (Tpanax Notoginseng pills and Lornoxicam injection group),12 patients were male
      and 8 patients were female; ranging in age from 23 to 42 years, averaged 31.0
      years; the disease course ranged from 3.5 to 25.0 h, with an average of 13.6 h.
      Twenty patients in group C (Tpanax Notoginseng pill, Lornoxicam injection and
      Tongmai decoction group), 14 patients were male and 6 patients were female;
      ranging in age from 21 to 44 years, averaged 31.5 years; the disease course
      ranged from 4.6 to 29.0 h, with an average of 13.3 h. Among all the patients, 42
      patients with fractures were fixed with femoral intramedullary nailing, and other
      18 patients with femoral locking plate fixation. The patients in group A took
      Tpanax Notoginseng pills orally, 4 g each time and twice daily; the patients in
      group B took Tpanax Notoginseng pills orally as group A, and at the same time
      received intramuscular injection of Lornoxicam, 8 mg each time and once daily;
      the patients in group C took Tpanax Notoginseng pills orally and received
      intramuscular injection of Lornoxicam as group B, and at the same time took
      Tongmai decoction (R ) orally, 200 ml each time and twice daily. The above
      medications were administered to the three groups on the second day after
      admission to hospital. Peripheral blood samples were taken for determination of
      pro-inflammatory cytokines of TNF-alpha and IL-6 in blood serum on the 2nd and
      6th days before operation and on the 8th and 13th days after operation. And all
      the patients were evaluated liver and kidney function at the 2nd and 7th days
      after admission. Analysis of variance and least significant difference-test were
      done with the help of SPSS 17.0 statistic software. RESULTS: The differences
      among three groups of TNF-alpha and IL-6 in blood serum at the 2nd day after
      admission and 2 days after operation had no statistical significance (P > 0.05).
      The TNF-alpha and IL-6 levels among 3 groups had statistical differences at the
      7th day after admission and at the 7th day after operation (P < 0.05, P < 0.01).
      There were significant differences of TNF-alpha and IL-6 levels between the 7th
      day after admission and the 2nd day after admission, the 7th day after operation
      and the 2nd day after admission (P < 0.01). There were also significant
      differences of TNF-alpha and IL-6 levels between group C compared with group A
      and B at the 7th day after admission and the 7th day after operation(P < 0.05, P
      < 0.01). CONCLUSION: The serum concentrations of TNF-alpha and IL-6 level
      significantly increased in perioperative period. The results indicate that the
      Tongmai decoction may play an important role in inhibiting the release of TNF
      alpha and IL-6 into the blood stream and decreasing the incunabula complication
      at early traumatic stage.

PMID- 20701122
TI  - [Treatment of serious burst thoracolumbar fracture with posterior pedicle screw
      fixation, transpedicular bone grafting and vertebral canaloplasty].
AB  - OBJECTIVE: To study the clinical results of posterior pedicle screw fixation,
      transpedicular bone grafting and vertebral canaloplasty with ilium autografting
      in treating serious burst thoracolumbar fracture. METHODS: From March 2004 to
      March 2008,10 patients with serious burst thoracolumbar fracture, including 7
      males and 3 females with age for 24-58 years (mean 41 years)were treated by
      posterior pedicle screw fixation, transpedicular bone grafting and total
      laminectomy with preservation of spinal process and vertebral canaloplasty with
      ilium autografting. The operative effects were assessed according to Frankel
      classification and radiologic results. RESULTS: All patients were followed up
      from 1 to 4 years. There was no loosening or broken in instrumentation. The
      anterior edge height of the fractured vertebrae body was restored from (21.00 +/-
      12.00)% to (95.00 +/- 4.20)%, and the posterior edge height of the fractured
      vertebrae body was restored from (70.00 +/- 15.00)% to (96.00 +/- 3.20)%
      postoperatively, which both demonstrated improvement compared with preoperative
      instance (P < 0.01). The Cobb angle was restored from (32.80 +/- 8.20) degrees to
      (4.20 +/- 1.60) degrees which also demonstrated improvement compared with the
      preoperative Cobb angle (P < 0.01). At least one grade recovery was observed in
      all cases except one patient with preoperative Frankel A degree. The result of
      Denis classification, P1, had 4 cases, P2 had 4, P3 had 1, P4 had 1. CONCLUSION:
      Posterior pedicle screw fixation, transpedicular bone grafting and vertebral
      canaloplasty can obtain satisfactory results treating serious burst thoracolumbar
      fractures. It is a feasible method with advantages of simple operation, good
      efficacy, preservation of structure of posterior column which should be applied
      clinically.

PMID- 20701123
TI  - [Combined posterior and anterior approaches for the treatment of cervical
      spondylotic myelopathy].
AB  - OBJECTIVE: To explore the efficacy of one stage or staging treatment of cervical
      spondylotic myelopathy through combined posterior and anterior approaches.
      METHODS: From June 2001 to October 2008, 45 patients with pinching cervical
      spondylotic myelopathy and developmental stenosis of cervical spinal canal were
      decompressed through combined posterior and anterior approaches in one stage or
      staging operation. Among the patients, 35 patients were male and 10 patients were
      female, ranging in age from 45 to 72 years, with an average of 53 years. Five
      patients were decompressed through combined posterior and anterior approaches in
      one-stage operation, and other 40 patients were treated in staging operation. All
      the patients were treated with open-door posterior cervical expansive
      laminoplasty and anterior decompression, bone graft and titanium plate internal
      fixation. JOA scores were used to evaluate the therapeutic effects at the 3rd
      month and one year after operation. RESULTS: After the treatment, 44 patients
      were followed up from 13 to 62 months, with an average of 30 months. One patient
      was dead of lung infection at the 21th day after operation. The nerve root palsy
      of C5 was found in 3 cases. One patient had postoperative hoarseness. Axial
      symptoms were found in 14 cases. Two patients had donor site complications. There
      were no screws broken or back out, no screw loosening, no moving or sinking of
      bone block or Ti-net, no door re-closer and cervical deformity. Forty-four
      patients got spinal fusion. According to JOA score criteria: the average
      preoperative JOA score was (9.36 +/- 2.24) points, JOA score was (12.34 +/- 2.64)
      points in 3 months after operation, (12.77 +/- 2.61) points in one year after
      operation. Among 44 cases, 16 got an excellent result, 19 good, 6 fair, 3
      invalid. There were statistically differences between preoperative score and 3
      months or one year after operation. CONCLUSION: Decompression through combined
      posterior and anterior approaches for the treatment of pinching cervical
      spondyoltic myelopathy and developmental stenosis of cervical spinal canal has
      good efficacy, as well as a safety operation method. The operation method with
      one or staging decompression through combined anterior and posterior approach
      should be chosen according to the conditions of the patients and the operations.
      Anterior decompression, bone graft and titanium plate internal fixation could
      restore the height of vertebral body effectively and prevent fusion complication.

PMID- 20701124
TI  - [Clinical analysis of vertebral laminae reconstruction after laminectomy and
      pedicle screw fixation in treating lumbar spinal stenosis].
AB  - OBJECTIVE: To observe the curative effects of vertebral laminae reconstruction
      after laminectomy and pedicle screw fixation for the treatment of lumbar spinal
      stenosis in early (at the 3rd months after operation) and metaphase (at the more
      than 1 year after operation). METHODS: Twenty-two patients with lumbar spinal
      stenosis were treated by vertebral laminae reconstruction after laminectomy and
      pedicle screw fixation, there were 12 males and 10 females, the age was from 55
      to 76 years with an average of 65.8 years, including single segment (6 cases),
      double segments (13 cases) and three segments (3 cases) of L3-S1. The follow-up
      period was for 1-3 years, preoperative and postoperative (at the 3rd months after
      operation and last follow-up) to assess the subjective symptoms, physical signs,
      the limit of daily activities and bladder function according to JOA scoring; and
      observe saggital diameter measurement and radiological changes through X-ray and
      CT. RESULTS: All the patients were followed up, the JOA scoring were respectively
      5.3 +/- 1.6, 23.2 +/- 2.0, 22.9 +/- 2.4 before operation and after operation (at
      the 3rd after operation and last follow-up); at the 3rd months after operation,
      18 cases obtain excellent results, 3 good, fair 1, and at the last follow-up, 17
      cases obtain excellent results, 3 good, fair 2, there was no significant
      difference between two postoperative periods (u = 0.413, P < 0.05). The mean
      sagittal diameter of narrow segment was respectively (6.8 +/- 0.9), (17.6 +/-
      2.5), (16.9 +/- 1.8) mm before operation, at the 3rd months after operation and
      the last follow-up. Through statistics processing, there was significant
      different comparing JOA scoring at 3 months after operation, last follow-up with
      preoperative (P < 0.05). There was significant difference of vertebral canal
      sagittal diameter between at the 3rd months after operation and before operation
      (t = 35.116, P < 0.01); there was no significant difference between at the 3rd
      months after operation and last follow-up (t = 1.814, P > 0.05). The CT
      examination of last follow-up showed the vertebral canal have no stenosis, the
      dural sac and nerve roots have no compression, the rebuilt vertebral laminae have
      fused well, the graft bone are no absorbed and the fixation have no failure.
      CONCLUSION: Treatment of lumbar spinal stenosis with vertebral lamina
      reconstruction after vertebral laminectomy and pedicle screw fixation can obtain
      satisfactory results in early and metaphase. The method had advantages of
      decompression thoroughly and fixation solidly, and could prevent vertebral canal
      restenosis causing by nerve oppression of the postoperative scar and nerve
      adhesion.

PMID- 20701125
TI  - [Clinical observation of mid-stage complications after cervical disc
      replacement].
AB  - OBJECTIVE: To summarize the therapeutic experience of Bryan prosthetic cervical
      disc replacement at the 3rd years after operation and to analyze the clinical
      effect, incidence rate of heterotopic ossification, conditions of prosthetic
      fusion in order to investigate the countermeasures. METHODS: From December 2005
      to December 2008, 54 patients with cervical syndrome (34 males and 20 females,
      the age was from 39 to 69 years with an average of 50.5) were treated with single
      level Bryan prosthetic cervical disc replacement. The patients were followed for
      24-36 months with an average of 30 months. The symptoms and nerve function were
      evaluated according to JOA and Odom's scoring. The anterior-posterior and lateral
      cervical X-ray films were also taken regularly every three months for the
      observation of heterotopic ossification and prosthetic fusion. Meanwhile, the X
      ray films of the forward bending, extending, left and right lateriflection were
      taken before operation and at the 1st years after operation for the measurement
      of the stability and rang (ROM) of replaced levels. RESULTS: The pain symptom and
      neurological function of all 54 patients were improved obviously. JOA score
      increased with an average of 76.1%, and ROM of replaced levels also improved
      obviously. The incidence rate of heterotopic ossification and prosthetic fusion
      went up year by year, 3.7% (2/54) for the first year, 16.7% (9/54) for the second
      year and 22.2% (12/54) for the nearly third year. CONCLUSION: Bryan prosthetic
      cervical disc replacement has better mid-stage results than conventional methods.
      Modified surgical methods and early rehabilitation exercise may reduce the
      relatively high incidence rate of heterotopic ossification and prosthetic fusion.

PMID- 20701126
TI  - [Analysis and countermeasure of complications in treating fracture of calcaneus
      with internal fixation].

PMID- 20701127
TI  - [Analysis of results on minimum 4-year follow-up of modified posterior lumbar
      interbody fusion for the treatment of isthmic spondylolisthesis].
AB  - OBJECTIVE: To investigate the long-term results of modified Jaslow technique to
      treat isthmic spondylolisthesis. METHODS: From April 2000 to January 2002, 75
      patients with isthmic spondylolisthesis (Meyerding grade I had 24 cases, grade II
      had 35, grade III had 16)were treated with a modified Jaslow technique using one
      single fusion cage on the symptomatic side. There were 35 males and 40 females
      with an average age of 40 years old, ranging from 23 to 71 years. Clinical
      symptoms included intermittent claudication, radicular pain and low back pain.
      Pre- and postoperative percentage slip, lumbar lordosis, height ratio of
      intervertebral space and the fusion ratio were analyzed according to radiographic
      conditions; Visual Analogue Pain Score (VAS), Oswestry Disability Index (ODI),
      Houshuxun criterion were applied to assess the pain and the conventional
      functions. RESULTS: All patients were followed up from 48 to 62 months with an
      average of 50.2 months. The percentage slip reduced from 35.6% preoperative to
      9.7% at the last follow-up (corrected 72.8%), lumbar lordosis from (53.6 +/-
      15.7) degrees to (51.2 +/- 17.1) degrees and the height ratio increased from
      (58.6 +/- 12.3)% to (91.5 +/- 11.2)%, the rate of fusion was 97.3% (73/75) at the
      last follow-up. The mean VAS and ODI before operation was (6.2 +/- 2.5) scores
      and (47.8 +/- 10.3)%, respectively, decreased to (2.5 +/- 1.9) scores and (10.3
      +/- 3.0)% at the last follow-up. There was statistical significance in all items
      except for lumbar lordosis. According to Houshuxun criterion, the results was
      excellent in 53 cases, good in 12, fair in 8 and poor in 2, the rate of excellent
      and good was 86.7%. Complication included 2 case internal fixation failure, 3
      cases transient neurologic deficits and 3 cases pseudoarticulation formation.
      CONCLUSION: The modified Jaslow technique is suitable for isthmic
      spondylolisthesis (Meyerding I - III), which has advantage of sufficient
      decompression, solid fixation and can obtain satisfactory clinical results with
      long-term follow-up.

PMID- 20701128
TI  - [Surgical treatment for injury of lateral ligament in ankle joint].

PMID- 20701130
TI  - [Application of Xiaozhiling injection and absolute alcohol in ultrasonic therapy
      for the popliteal cysts].

PMID- 20701129
TI  - [Comparison of effects of Wujia Bugu decoction) and alendronate sodium on
      protection the bone loss of hindlimb unloaded rats].
AB  - OBJECTIVE: To compare the effects of Wujia Bugu decoction and Alendronate sodium
      on protecting bone and muscle loss of hindlimb unloaded rats lasting three weeks.
      METHODS: March to May, 2009, 40 male Wistar rats with age of 6-week, were
      randomized divided to four groups (10 rats in each group): hindlimb unloaded
      group treated with Chinese medicine (HUC), hindlimb unloaded group treated with
      alendronate sodium (HUA), control group (CON), as well as hindlimb unloaded group
      (HU). During the experiment, rats of HUC was given Wujia Bugu decoction
      (including the Ciwujia, Shudihuang, Huainiuxi, Muli, etc. with the concentration
      of 0.704 g/ml) 10 ml/kg weight once a day, HUA was given quantitative alendronate
      sodium slice dissolve suspension (0.9 mg/ml) once a week. CON and HU were given
      double-distilled water. The experiment lasted 4 weeks,from the second to the
      forth week, rats in HU, HUC, HUA were hindlimb unloaded. All rats were sacrificed
      at the fourth weekend, the content of Ca, P and the activation of ALP in serum,
      Bone mineral density (BMD) of humerus and femurs, Biomechanical property of tibia
      and humerus, as well as the weight index of biceps and sural muscles were
      measured. RESULTS: Compared with CON, serum Ca of HU was significantly increased
      (P < 0.05), BMD, mechanical properties, muscle index of hindlimb were
      significantly reduce (P < 0.01), the serum Ca of HUA significantly increased (P <
      0.05). Serum ALP of HUC was significantly higher than other three groups (P <
      0.01). Compared with HU, femoral BMD of HUC and HUA significantly increased,
      tibial maximum load, maximum deflection and elastic load had increased tendency;
      calf muscle atrophy of HUC and HUA was alleviate 50% and 12.5% respectively (P >
      0.05), humeral BMD had no significant difference, while the maximum deflection (P
      < 0.01) and elastic deflection (P < 0.05) in humerus of HUA were significantly
      lower. CONCLUSION: Herbal prescription and alendronate sodium can effectively
      protect the bone and muscle loss of hindlimb unloaded rats, improve its
      mechanical structure. Herbal prescription has advantages of relieving mechanical
      properties change. The effects of Wujia Bugu decoction and alendronate sodium are
      similar in treating space weightlessness bone loss.

PMID- 20701131
TI  - [Effect of reinforcing Qi strength spleen in the expression of bFGF and EGF in
      treating serious soft tissue injury].
AB  - OBJECTIVE: Using the method of bleeding from the orbital vein and lancing to make
      the animal model of trauma, and to observe the influence of reinforcing Qi
      strength spleen in the expression of bFGF and EGF in the reparative process of
      raw surface, in order to explore the possible mechanism of reinforcing Qi
      strength spleen in promoting the rehabilitation of soft tissue. METHODS: Forty
      healthly adult SD rats were made to be traumatic model using the method of
      bleeding from the orbital vein and lancing. After operation, there were 33 rats
      survival, which were divided into the reinforcing Qi strength spleen group, the
      activating blood circulation to dissipate blood stasis group and the model group
      randomly. The raw surface and ambient normal skin were taken at the 3rd, 7th and
      14th days after operation to detect the expression of bFGF and EGF by
      immunohistochemical method. RESULTS: At the 3rd, 7th and 14th days after
      operation, the expression of bFGF and EGF in the tissue of raw surface of the
      reinforcing Qi strength spleen group and the activating blood circulation to
      dissipate blood stasis group was obviously higher than that of the model group(P
      < 0.05). Compared with the activating blood circulation to dissipate blood stasis
      group, the expression of bFGF and EGF in the tissue of raw surface of the
      reinforcing Qi strength spleen group was higher (P < 0.05) in the 3rd and 7th day
      after operation. But in the 14th after operation, there was no significantly
      difference between reinforcing Qi strength spleen group and activating blood
      circulation to dissipate blood stasis group. CONCLUSION: The method of
      reinforcing Qi strength spleen can efficiently promote the expression of bFGF and
      EGF in raw surface of serious soft tissue injury.

PMID- 20701132
TI  - [Experimental study of eliminat dampness resolv phlegm method in treating
      cervical spondylopathy of the vertebral artery type].
AB  - OBJECTIVE: To detect the velocity and viscosity of blood flow of the vertebral
      arteries, the apoptotic cell and apoptotic related protein in the brain in order
      to offer theoretical foundation for the treatment of cervical spondylopathy of
      the vertebral artery type with the eliminat dampness resolv phlegm method.
      METHODS: Sixty male Japanese big ear rabbits were divided randomly into normal
      sodium group (A), Flunarizine group (B), low dosage Wendantang group (C), large
      dosage Wendantang group (D), Flunarizine group combined with large dosage
      Wendantang group (E), normal group (F). Each group had 10 rabbits. Xiaozhiling
      injection was injected around the vertebral arteries of rabbits in group A, B C,
      D, E to make the model of the cervical spondylopathy of the vertebral artery
      type. Normal sodium (20 ml x kg(-1)d(-1)) was apply through intragastric
      administration in group A, F; Flunarizine (0.8 mg x kg(-1)d(-1)), low dosage
      Wendantang (1 g x ml(-1)d(-1)), large dosage Wendantang (2 g x ml(-1)d(-1)),
      Flunarizine combined with large dosage Wendantang were respectively apply through
      intragastric administration in group B, C, D, E. The velocity and viscosity of
      blood flow of the vertebral arteries, the apoptotic cell and apoptotic protein in
      the brain were detected before and after the treatment. RESULTS: Satisfactory
      animal model were obtained in group A, B, C, D, E. The rabbits of group E had the
      most improvement of the velocity and viscosity of blood flow of the vertebral
      arteries while at meantime, which had the lowest apoptotic index and apoptotic
      related protein expression in the brain. CONCLUSION: The routine treatment for
      the cervical spondylopathy of the vertebral artery combined with eliminat
      dampness resolv phlegm method could improve velocity and viscosity of blood flow
      of the vertebral arteries, which maybe relate with reduction of apoptosis in the
      brain.

PMID- 20701133
TI  - [Pathological zonation of gunshot wounds and its guidance on the treatment
      methods].
AB  - The Chinese investigators separated bullet wounds into three zones in the
      beginning of 1980s: a primary wound tract, a contusion zone adjacent to prinary
      wound tract, and a concussion zone neighboring the contusion zone. Basing on the
      research results by MRI scan and pathological observation, the author and his
      coworkers recently proposed that the gunshot wounds should be divided into four
      consecutive zones: a primary wound tract, a zone of coagulative necrosis, a zone
      of muscle disruption, and a zone of muscle distortion. A zone of coagulative
      necrosis plus a zone of muscle disruption equals to a contusion zone, they are
      separately named because the former is irreversibly devitalized and the latter
      still has the ability to recover. The sectionalized method shows the range of
      debridement and provide reference for the conservative treatment or thoroughly
      debridement. However, the mechanism of each zone need to be further studied.

PMID- 20701134
TI  - [Treatment of unstable pelvic fractures with minimally invasive internal
      fixation].
AB  - OBJECTIVE: To explore the clinical effects of minimally invasive internal
      fixation in the treatment of unstable pelvic fractures. METHODS: From January
      2005 to January 2009, the data of 48 patients with unstable pelvic fractures were
      retrospectively analyzed. There were 31 males and 17 females. The age ranged from
      12 to 66 years with an average of 37.8 years. Among them, 29 cases were caused by
      traffic accident, 14 by fall from height and 5 by crush injury. According to
      Tile's classification, type B1 was in 4 cases, B2 in 3, C1 in 25, C2 in 14 and C3
      in 2. All patients were treated with minimally invasive internal fixation of
      percutaneous reconstruction plate (including 20 cases with percutaneous pubic
      ramus screws fixation and 8 cases with pubic tubercle screws fixation) and
      percutaneous sacroiliac screws (including 16 cases with percutaneous pubic ramus
      screws fixation and 4 cases with pubic tubercle screws fixation). With X-ray
      films to observe the reduction of fractures and according to Majeed standard to
      evaluate the clinical effects. RESULTS: All patients were followed up for 12-39
      months with an average of 17 months. No infection of incision,nerve injuries,
      loosening or breakage of the screw was found. All cases attained bone union.
      Anatomical reduction achieved in 29 cases,satisfactory reduction 18 cases, and
      unsatisfactory reduction 1 case. According to the Majeed standards, 29 cases
      obtained excellent results, 15 good and 4 fair, the rate of excellent and good
      was 91.7%. CONCLUSION: Treatment of unstable pelvic fractures with minimally
      invasive internal fixation had advantages of minimal trauma, less bleeding, less
      postoperative complications, high bone union rate, reliable fixation and
      satisfactorily functional recovery after operation, but the method demanded
      skillful surgical techniques.

PMID- 20701135
TI  - [The application of C1-2 pedicle screw fixation in treating atlantoaxial
      instability].
AB  - OBJECTIVE: To explore the feasibility of C1-2 pedicle screw fixation and fusion
      technique in treating atlantoaxial instability. METHODS: From January 2006 to
      January 2009,18 patients with atlantoaxial instability were treated with C1-2
      pedicle screws and plates fixation under general anesthesia. There were 11 males
      and 7 females, the age for 17-62 years with the mean of 37.7 years. The course of
      disease was from 3 days to 30 months with an average of 10.6 months. The patients
      had different degrees neck pain and disturbance of sensation or (and) dyskinesia,
      had atlantoaxial instability from images before operation. The JOA scoring before
      operation were from 8 to 15 with an average of 11.4. Bone fusion of patients was
      observed with X-rays, CT and MR image at the same time after operation and the
      JOA scoring was compared with preoperative. RESULTS: A total of 72 screws were
      successfully placed in 18 cases, among them, 15 cases were followed up from 6 to
      24 months with an average of 11.5 months. Fifteen cases obtained bone fusion with
      time for 3-6 months without the complications of internal fixation failure or
      redislocation of atlas. The spinal compression had differently improved,
      postoperative JOA scoring was from 12 to 17 scores with an average of 14.5
      scores. CONCLUSION: Pedicle screw fixation and fusion in atlas has advantages of
      firm fixation and high fusion rate, it is a better choices for atlantoaxial
      instability. It is not suitable for variations of sulcus of vertebral artery of
      atlas and posterior arch of atlas.

PMID- 20701136
TI  - [Observation of long-term efficacy of visco-supplementation with sodium
      hyaluronate in treating knee osteoarthritis].
AB  - OBJECTIVE: To retrospectively analyze the long-term efficacy of intra-articular
      injection with sodium hyaluronate for the treatment of knee osteoarthritis.
      METHODS: From January 2006 to August 2007,120 patients (181 knees) with knee
      osteoarthritis, (mild 61 knees, moderate 72 knees, severe 48 knees), were treated
      by intra-articular injection with sodium hyaluronate, 2 ml every week for 5
      weeks. The clinical effects were analyzed according to VAS, JOA scoring before
      treatment, at the 1 month, 1, 2 years after treatment. RESULTS: (1) VAS scores
      were respectively (7.26 +/- 1.83), (1.85 +/- 1.21), (2.54 +/- 1.40), (3.07 +/-
      1.51) scores before treatment, at the 1 month, 1 and 2 years after treatment.
      There was significant difference between every post-treatment and pre-treatment.
      (2) JOA scoring of knee function was respectively (18.7 +/- 6.6), (84.3 +/-
      15.5), (75.4 +/- 22.4), (64.8 +/- 25.6) scores before treatment, at the 1 month,
      1 and 2 years after treatment. There was significant difference between every
      post-treatment and pre-treatment. (3) Assessment of long-term efficacy among 181
      knees who were followed up 1 year, 70 cases got excellent results, 54 good, 34
      fair and 23 poor. Those who were followed up 2 years,40 cases got excellent
      results, 54 good, 53 fair and 34 poor. Knee function became poor along with time
      lapse. The efficiency was respectively 86.89% (53/61), 79.17% (57/72), 54.17%
      (26/48) in mild knees, moderate knees, severe knees at the 2 years after
      treatment. CONCLUSION: The long-term efficacy of intra-articular injection with
      sodium hyaluronate is satisfactory in treating knee osteoarthritis. The efficacy
      is better for mild and moderate osteoarthritis than for the severe
      osteoarthritis. The short-term efficacy is acceptable and the long-term one is
      worse for the severe knees.

PMID- 20701137
TI  - [Diagnosis of cervical spondylotic myelopathy with MRI of low magnetic field].

PMID- 20701138
TI  - [Treatment of diastatic fracture of the distal humeral epiphysis in children with
      manipulative reduction].

PMID- 20701139
TI  - [Treatment of calcaneus fractures using a minimally invasive sinus tarsi
      approach].

PMID- 20701140
TI  - [The diffuse-type tenosynovial giant cell tumor in ankle joint: a case report].

PMID- 20701141
TI  - [Mechanism and progressing study in promoting wound healing with negative
      pressure therapy].
AB  - Negative pressure therapy (NPT) has been widely used in clinic and obtained
      obvious curative effects. However, its mechanism has been relatively less
      studied. This article updated the enhancing mechanism, physical action and
      biomechanics effects, etc. and provided thinking for the further development of
      NPT.

PMID- 20701142
TI  - [Treatment of anterior hip dislocation associated with ipsilateral
      subtrochanteric fracture: a case report].

PMID- 20701143
TI  - [Progressing study in osteoblasts cultured in vitro].
AB  - With the development of cell culture technology in vitro, people have
      successfully cultivated osteoblast cells of typical characteristics from a number
      of animal skull, bone marrow, periosteum and bone tissues; studies have shown
      that these osteoblasts have good biological characteristics, can create bone
      tissue in different environments, can apply joint stand for the construction of
      tissue engineered bone, be implanted in the body to repair bone defects. In this
      article, the source of osteoblast, regulatory factor, composite graft and Chinese
      medicine research progress were reviewed.

PMID- 20701144
TI  - [Analysis of misdiagnosed reason and discussing its countermeasures for 81
      patients with the third lumbar transverse process syndrome].

PMID- 20701145
TI  - [Decision on financing model for new specialist education is needed].

PMID- 20701146
TI  - [What is evidence-based practice in insufficient nerve block?].

PMID- 20701147
TI  - [Shortsighted economics behind the choice of HPV vaccine. Sweden misses the
      chance the chance "to eradicate" condyloma].

PMID- 20701148
TI  - [Suspected lice eggs in the hair of a boy revealed dangerous parasite].

PMID- 20701149
TI  - [Large variations in carotid surgery. A questionnaire to surgical units shows
      different procedures].

PMID- 20701150
TI  - ["Epidemic" increase of tonsillar and base of tongue cancer. Explanation:
      parallel increase of HPV infections].

PMID- 20701151
TI  - [Caveolae-invaginations in the cell membrane with complex function. Defects in
      caveolae gene connected to severe congenital diseases].

PMID- 20701152
TI  - [The first year with colorectal cancer screening in Stockholm. Careful monitoring
      and quality control of the whole process is necessary].

PMID- 20701153
TI  - ["Recognize emergency care as a separate specialty"].

PMID- 20701154
TI  - [EU expert improves influence in health care matters].

PMID- 20701155
TI  - [The Dental and Pharmaceutical Benefits Agency misinterpret its mission].

PMID- 20701156
TI  - [Good care and properly used beds most important].

PMID- 20701157
TI  - Left out of the loop.

PMID- 20701159
TI  - A life on the ocean wave.
AB  - Setting sail on a new career path as a nurse responsible for the health of the
      passengers and crew of cruise liners can be hugely satisfying.

PMID- 20701158
TI  - Community nurses face a future where change is the only certainty.

PMID- 20701160
TI  - Cases in the balance.
AB  - A day spent watching a fitness for practice panel reinforced what Michael Traynor
      found in the literature about referrals to the nurse regulator.

PMID- 20701161
TI  - The clock is ticking on wards.
AB  - The role of recently qualified nurses is examined as part of a series in which
      RCN fellows look at the challenge of improving nursing care.

PMID- 20701163
TI  - Seeing out their last days with dignity.

PMID- 20701162
TI  - Missing a link.
AB  - New treatments for rheumatoid arthritis might be behind the increase in
      listeriosis in older people.

PMID- 20701164
TI  - Recognition, assessment and management of anaphylaxis.
AB  - This article describes the physiological changes that take place during
      anaphylaxis, explores the ABCDE (airway, breathing, circulation, disability,
      exposure) approach to patient assessment and discusses the pharmacological
      interventions required to treat anaphylaxis effectively.

PMID- 20701165
TI  - Assessment of older adults in the emergency department.
AB  - Older people make extensive use of emergency departments, yet there is evidence
      that optimum care is difficult to provide for those with complex health and
      social problems. Inappropriate hospital admissions for older people have also
      been documented. This article describes the establishment of an assessment team
      for older people (ATOP) that has been created to address these issues in a
      district general hospital. In the four months of the study period, the ATOP
      prevented admission of 178 of the 666 patients seen. Of these 178 patients, 19 re
      attended the hospital and six were admitted.

PMID- 20701166
TI  - Understanding the needs of women with postnatal depression.
AB  - This article provides an overview of postnatal depression, including strategies
      to detect the disorder, suggested referral pathways and examples of evidence
      based interventions. The article is aimed at health and social care professionals
      involved in working with women and their families during pregnancy or in the
      postnatal period.

PMID- 20701167
TI  - Managing sepsis.

PMID- 20701168
TI  - Criminal backgrounds.

PMID- 20701169
TI  - A lighter side of life.

PMID- 20701170
TI  - Test for the best.

PMID- 20701171
TI  - Healthcare ethics: the experience after the Haitian earthquake.
AB  - On January 12, 2010, a 7.0 Richter earthquake devastated Haiti and its public
      health infrastructure leading to a worldwide humanitarian effort. The United
      States sent forces to Haiti's assistance including the USNS Comfort, a tertiary
      care medical center on board a ship. Besides setting a transparent triage and
      medical regulating system, the leadership on the Comfort instituted a
      multidisciplinary Healthcare Ethics Committee to assist in delivering the highest
      level efficient care to the largest number of victims. Allocation of resources
      was based on time-honored ethics principles, the concept of mass casualty triage
      in the setting of resource constraints, and constructs developed by the host
      nation's Ministry of Health. In offering aid in austere circumstances, healthcare
      practitioners must not only adhere to the basic healthcare ethics principles but
      also practice respect for communities, cultures, and traditions, as well as
      demonstrate respect for the sovereignty of the host nation. The principles
      outlined herein should serve as guidance for future disaster relief missions.
      This work is in accordance with BUMEDINST 6010.25, Establishment of Healthcare
      Ethics Committees.

PMID- 20701172
TI  - Pediatric issues in disaster management, part 2: evacuation centers and family
      separation/reunification.
AB  - Although children and infants are likely to be victims in a disaster and are more
      vulnerable in a disaster than adults, disaster planning and management has often
      overlooked the specific needs of pediatric patients. We discuss key components of
      disaster planning and management for pediatric patients including emergency
      medical services, hospital/facility issues, evacuation centers, family
      separation/reunification, children with special healthcare needs, mental health
      issues, and overcrowding/surge capacity. Specific policy recommendations and an
      appendix with detailed practical information and algorithms are included. The
      first part of this three part series on pediatric issues in disaster management
      addresses the emergency medical system from the field to the hospital and surge
      capacity including the impact of crowding. The second part addresses the
      appropriate set up and functioning of evacuation centers and family separation
      and reunification. The third part deals with special patient populations: the
      special healthcare needs patient and mental health issues.

PMID- 20701173
TI  - Utilizing paramedics for in-patient critical care surge capacity.
AB  - INTRODUCTION: While many hospitals have developed preliminary emergency
      department and in-patient surge plans, the ability to surge is often limited by
      critical resources. The resource which is often the most limited is usually the
      human resource and within this category the limiting factor is almost universally
      nursing. As a result, nursing shortages can result in an inability of a hospital
      or emergency department to create surge capacity to deal with large numbers of
      ill or injured patients. Utilizing paramedics in acute-care hospitals or at
      alternate care sites could serve as expansion staff to supplement existing
      nursing staff allowing fewer nurses to care for a larger numbers of patients
      during a disaster, act of terrorism, or public health emergency. While the
      procedures performed for nursing do vary from hospital to hospital, there are
      national certifications for both emergency nursing (CEN) and critical care
      nursing (CCRN) that can be used to establish a standard for comparison. METHODS:
      A detailed review and curriculum mapping of the specific educational objectives
      and competencies of the U.S. Department of Transportation National Standard
      Curriculum for the Emergency Medical Technician-Paramedic as well as the
      competencies and criteria for board certification as a Certified Emergency Nurse
      (CEN) and Critical Care Registered Nurse (CCRN) was performed. RESULTS:
      Approximately 90 percent of the CEN and CCRN knowledge skills and competencies
      are met or exceeded by the National Standard Paramedic Curriculum. CONCLUSIONS:
      With appropriate training and orientation, paramedics may be used in an in
      patient setting to augment emergency and critical care nursing staff during a
      disaster, act of terrorism, or public health emergency.

PMID- 20701174
TI  - O2C3: A unified model for emergency operations planning.
AB  - The leadership in each jurisdiction of the world has been described as legally,
      morally, and politically responsible for ensuring that necessary and appropriate
      actions are taken to protect people and property from the consequences of
      emergencies and disasters. As emergencies often evolve rapidly and become too
      complex for effective improvisation, a government can successfully discharge its
      emergency management responsibilities only by taking action beforehand. This
      requires preparedness in advance of the disaster event. Accordingly, preparedness
      measures should not be improvised or handled on an ad hoc basis.

PMID- 20701175
TI  - Hurricane Katrina experience and the risk of post-traumatic stress disorder and
      depression among pregnant women.
AB  - OBJECTIVE: Little is known about the effects of disaster exposure and intensity
      on the development of mental disorders among pregnant women. The aim of this
      study was to examine the effect of exposure to Hurricane Katrina on mental health
      in pregnant women. DESIGN: Prospective cohort epidemiological study. SETTING:
      Tertiary hospitals in New Orleans and Baton Rouge, U.S.A. PARTICIPANTS: Women who
      were pregnant during Hurricane Katrina or became pregnant immediately after the
      hurricane. MAIN OUTCOME MEASURES: Post-traumatic stress disorder (PTSD) and
      depression. RESULTS: The frequency of PTSD was higher in women with high
      hurricane exposure (13.8 percent) than women without high hurricane exposure (1.3
      percent), with an adjusted odds ratio (aOR) of 16.8 (95% confidence interval: 2.6
      106.6) after adjustment for maternal race, age, education, smoking and alcohol
      use, family income, parity, and other confounders. The frequency of depression
      was higher in women with high hurricane exposure (32.3 percent) than women
      without high hurricane exposure (12.3 percent), with an aOR of 3.3 (1.6-7.1).
      Moreover, the risk of PTSD and depression increased with an increasing number of
      severe experiences of the hurricane. CONCLUSIONS: Pregnant women who had severe
      hurricane experiences were at a significantly increased risk for PTSD and
      depression. This information should be useful for screening pregnant women who
      are at higher risk of developing mental disorders after a disaster.

PMID- 20701177
TI  - The world on a collision course and the need for a new economy.
AB  - The first part of the paper is an attempt to demonstrate that what we are going
      through at the present time is not just an economic-financial crisis, but a
      crisis of humanity. It seems that for the first time in human history several
      crises converge to simultaneously reach their maximum level of tension. The
      dominant economic model is to a great degree responsible for the world's
      collision course. Hence a number of myths that sustain the model are listed and
      analyzed. It is argued that a new economy, coherent with the problematiques of
      the twenty first century, needs urgently to be devised. The second part proposes
      the foundations for a new economy based on five fundamental postulates that allow
      the construction of transdisciplinary, holistic, and systemic visions to
      adequately understand the interdependence of all the elements that sustain life.
      It is stressed that it is no longer acceptable that Universities still teach
      economic theories of the nineteenth century in order to tackle twenty first
      century problems that have no precedence.

PMID- 20701176
TI  - Hard times call for creative solutions: medical improvisations at the Israel
      Defense Forces Field Hospital in Haiti.
AB  - Mass disaster medicine is characterized by the need to manage limited resources
      that are far inadequate to meet the population's demands. Under these hectic
      conditions, lack of specific medical equipment is expected and requires
      improvisation using available items. We describe the innovative use of medical
      improvisations at the Israel Defense Forces field hospital, working in the
      earthquake zone, Port-au-Prince, Haiti, on January 2010. Creative solutions were
      found to several problems in a variety of medical fields: blood transfusion,
      debridement and coverage of complex wounds, self-production of orthopedic
      hardware, surgical exposure, and managing maxillofacial injuries. We hope that
      the methods described will help to inspire medical teams working in disaster
      regions.

PMID- 20701178
TI  - The fallacies of concurrent climate policy efforts.
AB  - Climate policy has assumed an extreme degree of urgency in the international
      debate in recent years. This article begins by taking a critical look at the
      scientific underpinnings of the efforts to stabilize the climate. It points to
      several serious question marks on the purported relationship between greenhouse
      gas emissions and global warming, and expresses distrust about claims of
      impending catastrophes related to rising sea levels, hurricanes, and spread of
      infectious disease. It then reviews the concurrent climate policy efforts and
      concludes that they are incoherent, misguided and unduly costly, and that they
      have so far had no perceptible impact on anthropogenic greenhouse gas emissions.
      The exceedingly ambitious policy plans currently under preparation suffer from
      similar fallacies. For these reasons, but also because of the remaining
      scientific doubts and the exorbitant costs that have to be incurred, skepticism
      is expressed about the preparedness to implement the climate policy plans
      currently on the table.

PMID- 20701179
TI  - Climate policy to defeat the green paradox.
AB  - Carbon dioxide emissions have accelerated since the signing of the Kyoto
      Protocol. This discouraging development may partly be blamed on accelerating
      world growth and on lags in policy instruments. However, it also raises serious
      question concerning whether policies to reduce CO2 emissions are as effective as
      generally assumed. In recent years, a considerable number of studies have
      identified various feedback mechanisms of climate policies that often erode, and
      occasionally reinforce, their effectiveness. These studies generally focus on a
      few feedback mechanisms at a time, without capturing the entire effect. Partial
      accounting of policy feedbacks is common in many climate scenarios. The IPCC, for
      example, only accounts for direct leakage and rebound effects. This article
      attempts to map the aggregate effects of different types of climate policy
      feedback mechanisms in a cohesive framework. Controlling feedback effects is
      essential if the policy measures are to make any difference on a global level. A
      general conclusion is that aggregate policy feedback mechanisms tend to make
      current climate policies much less effective than is generally assumed. In fact,
      various policy measures involve a definite risk of 'backfiring' and actually
      increasing CO2 emissions. This risk is particularly pronounced once effects of
      climate policies on the pace of innovation in climate technology are considered.
      To stand any chance of controlling carbon emissions, it is imperative that
      feedback mechanisms are integrated into emission scenarios, targets for emission
      reduction and implementation of climate policy. In many cases, this will reduce
      the scope for subsidies to renewable energy sources, but increase the scope for
      other measures such as schemes to return carbon dioxide to the ground and to
      mitigate emissions of greenhouse gases from wetlands and oceans. A framework that
      incorporates policy feedback effects necessitates rethinking the design of the
      national and regional emission targets. This leads us to a new way of formulating
      emission targets that include feedback effects, the global impact target. Once
      the full climate policy feedback mechanisms are accounted for, there are probably
      only three main routes in climate policy that stand a chance of mitigating global
      warming: (a) returning carbon to the ground, (b) technological leaps in zero
      emission energy technology that make it profitable to leave much carbon in the
      ground even in Annex II countries and (c) international agreements that make it
      more profitable to leave carbon in the ground or in forests.

PMID- 20701180
TI  - Profitable solutions to climate, oil, and proliferation.
AB  - Protecting the climate is not costly but profitable (even if avoided climate
      change is worth zero), mainly because saving fuel costs less than buying fuel.
      The two biggest opportunities, both sufficiently fast, are oil and electricity.
      The US, for example, can eliminate its oil use by the 2040s at an average cost of
      $15 per barrel ($2000), half by redoubled efficiency and half by alternative
      supplies, and can save three-fourths of its electricity more cheaply than
      operating a thermal power station. Integrative design permits this by making big
      energy savings cheaper than small ones, turning traditionally assumed diminishing
      returns into empirically observed expanding returns. Such efficiency choices
      accelerate climate-safe, inexhaustible, and resilient energy supply-notably the
      "micropower" now delivering about a sixth of the world's electricity and 90% of
      its new electricity. These cheap, fast, market-financeable, globally applicable
      options offer the most effective, yet most underestimated and overlooked,
      solutions for climate, proliferation, and poverty.

PMID- 20701181
TI  - Food security: crops for people not for cars.
AB  - Humankind is currently faced with the huge challenge of securing a sustainable
      energy supply and biofuels constitute one of the major options. However, the
      commercially traded edible crops are barely sufficient to meet food demand of the
      present world population. Certain regions, for example EU-27, do not even have a
      sufficient indigenous crop production. Of this follows that motor biofuels based
      on edible crops should be avoided. To replace more than some percent of the
      fossil motor fuels, non-edible biomass-rest products and wastes-should instead be
      considered for conversion to biofuels. In this way, about 10% of the current
      fossil fuels can be replaced. Feeding a world population expected to grow by some
      50% during the next 50 years will be a major challenge. For environmental reasons
      it seems that agricultural land cannot be expanded very much, maybe not at all.
      The solution to the increasing food demand seems therefore to be using the
      present crop production more efficiently and increasing output from present
      agricultural land, maintaining biodiversity and climate stability within
      reasonable limits. In the future, agriculture will need more energy and more
      water irrigation. Food production is, however, already very energy demanding,
      requiring several times more externally provided energy than the energy content
      of the food itself. A sufficient energy supply will be a key issue for the future
      farming!

PMID- 20701182
TI  - The quadruple squeeze: defining the safe operating space for freshwater use to
      achieve a triply green revolution in the anthropocene.
AB  - Humanity has entered a new phase of sustainability challenges, the Anthropocene,
      in which human development has reached a scale where it affects vital planetary
      processes. Under the pressure from a quadruple squeeze-from population and
      development pressures, the anthropogenic climate crisis, the anthropogenic
      ecosystem crisis, and the risk of deleterious tipping points in the Earth system
      the degrees of freedom for sustainable human exploitation of planet Earth are
      severely restrained. It is in this reality that a new green revolution in world
      food production needs to occur, to attain food security and human development
      over the coming decades. Global freshwater resources are, and will increasingly
      be, a fundamental limiting factor in feeding the world. Current water
      vulnerabilities in the regions in most need of large agricultural productivity
      improvements are projected to increase under the pressure from global
      environmental change. The sustainability challenge for world agriculture has to
      be set within the new global sustainability context. We present new proposed
      sustainability criteria for world agriculture, where world food production
      systems are transformed in order to allow humanity to stay within the safe
      operating space of planetary boundaries. In order to secure global resilience and
      thereby raise the chances of planet Earth to remain in the current desired state,
      conducive for human development on the long-term, these planetary boundaries need
      to be respected. This calls for a triply green revolution, which not only more
      than doubles food production in many regions of the world, but which also is
      environmentally sustainable, and invests in the untapped opportunities to use
      green water in rainfed agriculture as a key source of future productivity
      enhancement. To achieve such a global transformation of agriculture, there is a
      need for more innovative options for water interventions at the landscape scale,
      accounting for both green and blue water, as well as a new focus on cross-scale
      interactions, feed-backs and risks for unwanted regime shifts in the agro
      ecological landscape.

PMID- 20701183
TI  - Wales: leading the way.

PMID- 20701184
TI  - Unite will 'fight these cuts'.

PMID- 20701185
TI  - Perinatal depression in men: fathers' needs remain unmet.

PMID- 20701186
TI  - Preventing the preventable.

PMID- 20701187
TI  - The joys and challenges of semi-structured interviewing.
AB  - Semi-structured interviewing is an important tool for gathering data in
      qualitative research. This paper explores some of the joys and challenges
      associated with research interviewing. It discusses some of the basic skills
      required to do interviewing well, some of the difficulties associated with
      interviewing on a practical and emotional level, and how to address them. Being a
      good interviewer in a research context means to be aware of the responsibility
      for the participants' wellbeing as well as one's own. Good listening skills and
      emotional control are among the most crucial skills to develop. This paper
      summarises some of the skills needed to remain or become a professional,
      empathetic and ethical interviewer in the context of community practice. If some
      basic guidelines are followed and combined with practice, the craft of
      interviewing can become an art.

PMID- 20701188
TI  - Understanding leadership in community nursing in Scotland.
AB  - There is limited evidence concerning leadership in community nursing. NHS policy
      also fails to clarify and define what leadership is, though regarding it as key
      to developing safe and high quality care. This paper reports the findings of a
      research study that aimed to identify how leadership is perceived and experienced
      by community nurses, and to examine the interaction between recent policy and
      leadership development in community nursing. Mixed qualitative methods were used
      involving 31 individual interviews and three focus groups with community nurses
      and nurse leaders (n-39) in three health boards in Scotland. Findings indicate
      the leadership qualities valued by participants, including the importance of
      leaders' visibility. Team leaders in particular were recognised for their
      visibility and clinical leadership. Strategic and professional leadership was
      less evident, so acting as a barrier to the development of the profession. The
      strategic vision was often not clear to community nurses, and they engaged in
      differing ways with the strategies and action plans of senior nurse leaders. New
      leadership roles, like change, need time to evolve and new leaders need space and
      the education to develop leadership. Future leaders in community nursing need to
      focus beyond clinical leadership, ensuring that good leadership is a process
      requiring interdependence between leaders and followers.

PMID- 20701189
TI  - Breastfeeding experiences of mothers from disadvantaged groups: a review.
AB  - Despite the World Health Organization promoting breastfeeding as the optimal
      feeding method for infants, the breastfeeding initiation rates within these
      disadvantaged groups' remains low. It is important to identify the factors that
      prevent these groups from initiating and establishing successful breastfeeding.
      This review aims to identify the breastfeeding experiences of teenage mothers and
      mothers from low income groups. Qualitative research papers were identified using
      electronic and manual searches by following a systematic methodology. Nine
      relevant articles were critically analysed using a qualitative Critical Appraisal
      Skills Programme tool. Coding of the nine papers generated six themes. The
      benefits of breastfeeding known to these mothers were often superseded by the
      perceived barriers of breastfeeding, while the decision to breastfeed was
      frequently influenced by their social support network and prior exposure to
      breastfeeding. Disadvantaged mothers may require extra input and support to
      overcome any problems associated with breastfeeding. Developing healthcare
      professionals' capabilities to educate these disadvantaged groups, their social
      networks and the public about breastfeeding is crucial if it is to become
      established within our society.

PMID- 20701190
TI  - Weighing up the SEF.

PMID- 20701191
TI  - Happy family eating.

PMID- 20701192
TI  - Childhood constipation.
AB  - Idiopathic constipation in childhood is a problem that can cause a myriad of
      difficulties to both the child or young person and their family. There are a
      number of precipitating factors that may result in painful or infrequent bowel
      movements and/or soiling. Empowering children and young people together with
      their parents and carers forms one part of the treatment plan, but it is the
      adequate and effective use of laxative therapy alongside diet and lifestyle
      modifications and appropriate advice and support that can best help children to
      overcome this poorly understood condition. Professionals need to demystify how
      the bowel works and help children and young people to overcome their
      embarrassment in seeking help for this common childhood condition. The new NICE
      guideline will help all practitioners in recognising their role in helping
      children, young people and their families.

PMID- 20701193
TI  - Opening minds.

PMID- 20701194
TI  - The recent Surgical Safety Saves Lives Workshop in Vancouver.

PMID- 20701195
TI  - Conflict in the operating room: fight and flight or growth and communication.
AB  - Conflict is partial to no one. It ranges from within an individual and spirals in
      a ripple effect to others. Conflict among Registered Nurses (RNs) and Operating
      Room Technicians (ORTs) and between fellow RNs is prevalent in the operation
      room. The OR environment is filled with a number of personalities, each
      possessing varying methods for the implementation of patient care. Effective
      communication is key to preventing, and resolving, conflict situations.

PMID- 20701196
TI  - Quality improvement--a continuing focus.

PMID- 20701197
TI  - Head, shoulder, knees and toes!

PMID- 20701198
TI  - Whistleblowing...

PMID- 20701199
TI  - Shifting operating department practice to a graduate workforce.

PMID- 20701200
TI  - Clinical and cost effectiveness of urethral catheterisation: a review.
AB  - Reducing the number of catheter-associated urinary tract infections (CAUTI) in
      the National Health Service (NHS) has the potential for large cost savings. This
      review identifies factors which affect the incidence rate of CAUTI, as well as
      the need for further studies investigating cost-effectiveness, particularly in
      the areas of silver alloy catheters and education.

PMID- 20701201
TI  - Perioperative care: it's all a matter of competency--isn't it?
AB  - Many operating department practitioners believe that career success depends
      solely on technical ability. In this article Anne Raven-Vause challenges the
      nature of competent performance in busy perioperative settings and explores the
      skill set that needs to be developed in tomorrow's leaders.

PMID- 20701202
TI  - Patient care in the perioperative environment.
AB  - This article focuses on issues relating to patient positioning, by providing an
      overview of various patient positions, pressure area care and an awareness of
      some preventative measures to ensure safe patient care.

PMID- 20701203
TI  - Common fractures and injuries of the ankle and foot: functional anatomy, imaging,
      classification and management.
AB  - The ankle and foot are functionally important and complex joints. Bony fractures
      and ligamentous injuries are common. In this review paper we will discuss the
      functional anatomy, imaging, classification and the management of common ankle
      and foot injuries including ankle fractures, Achilles tendon ruptures, Lisfranc
      joint injuries, calcaneo fractures and fractures of the metatarsals and
      phalanges.

PMID- 20701204
TI  - Work-based learning: supporting advanced perioperative practice.
AB  - The arrival of work-based learning awards in professional education offers an
      alternative route for healthcare professionals looking to undertake post
      registration education. The unique way that work-based learning integrates
      individual learning needs with that of role requirements makes the award an ideal
      choice for the advanced perioperative practitioner (APP) who wishes to combine
      academic study with professional development. As an experienced and
      professionally qualified practitioner (Thatcher 2003) the APP will have an
      accumulation of knowledge, skills and experience that may go unrecognised in
      alternative awards. The term APP refers to a nurse, ODP or allied healthcare
      professional who undertakes a role that challenges the traditional boundaries of
      care within the perioperative environment (Radford 2004), such as that of a
      surgical care practitioner (SCP). Here Julie Quick, a SCP, examines the changes
      within post-registration education and in particular describes why work-based
      learning awards may be an appropriate choice for practitioners working at a
      higher level of practice.

PMID- 20701205
TI  - The early days of surgery for abdominal aortic aneurysm.
AB  - Aneurysms of the abdominal aorta, usually due to arteriosclerosis, have been long
      recognised as presenting a formidable challenge to the surgeon. At first
      symptomless, the aneurysm then presents as a pulsatile swelling. Once it reaches
      about 6 cm in diameter, it is at risk of rupture, and this danger increases as
      the mass gets larger. Untreated, of course, rupture means death from massive
      haemorrhage.

PMID- 20701206
TI  - Racial Discrimination Act must be reinstated in NT.

PMID- 20701207
TI  - A nurse's journey from caring to HIV.

PMID- 20701208
TI  - When is a life a life?

PMID- 20701209
TI  - ANF: 85 years and standing strong.

PMID- 20701210
TI  - Bed safety off the rails.

PMID- 20701211
TI  - New role for midwives promoting dental health.

PMID- 20701212
TI  - The implanted cardiac defibrillator.

PMID- 20701213
TI  - Peri-implantitis in a specialist clinic of periodontology. Clinical features and
      risk indicators.
AB  - Implant therapy has become a widely recognized treatment alternative for
      replacing missing teeth. Several long term follow-up studies have shown that the
      survival rate is high. However, complications may appear and risk indcators
      associated with early and late failures have been identified. The purpose of the
      present retrospective clinical study was to describe some clinical features of
      patients with clinical signs of peri-implantitis and to identify risk indicators
      of peri-implantitis in a population at a specialist clinic of Periodontology. In
      total,the material consisted of 377 implants in 111 patients with the diagnosis
      peri-implantitis. The mean age at the examination was found to be 56.3 years
      (range 22-83) for females and 64.1 years (range 27-85) for males. The mean number
      of remaining teeth was found to be 10.5 (S.D. 8.89) and the mean number of
      implants was 5.85 (S.D. 3.42). For a majority of the subjects, more than 50% of
      the remaining teeth had a marginal bone loss of more than 1/3 of the root length.
      Forty-sex percent of the patients visited regularly dental hygienists for
      supportive treatment. The percentage of implants with peri-implantitis was
      significantly increased for smokers compared to non-smokers (p = 0.04). In the
      group of non-smokers, 64% of the implants had the diagnosis peri-implantitis,
      while the corresponding relative frequency for smokers was 78%. A majority of the
      individuals had a Plaque index and Bleeding on probing index >50%. The median of
      the follow-up time after implant placement was 7.4 years and the observation
      period was not significantly correlated to the degree of bone loss around the
      implants. Among the subjects with a mean bone loss >6 mm at implants with peri
      implantitis, more than 70% had a mean marginal bone loss > 1/3 of the root length
      of the remaining teeth. A positive and significant correlation was found between
      the degree of marginal bone loss in remaining teeth and the degree of bone loss
      around implants with peri-implantitis. In conclusion, the results of the present
      study indicate that smoking as well as previous history of periodontitis are
      associated with peri-implantitis and may represent risk factors for this disease.

PMID- 20701214
TI  - Influence of education level and experience on detection of approximal caries in
      digital dental radiographs. An in vitro study.
AB  - This study evaluated whether variations in education level and experience among
      dental staff influence the diagnostic accuracy of carious lesions on digital
      radiographs. Three student groups and a fourth group of general practitioners
      (Dentists) with more than five years of clinical experience participated in this
      study.The student groups were (i) dental students in their final (tenth) semester
      (DS-10), (ii) dental students in the sixth semester (DS-6) who just finished
      dental radiology training, and (iii) dental hygiene students (DHS) in their final
      (fourth) semester. Seven observers from each group participated. Standard
      radiographs of 100 extracted teeth (premolars and molars) were taken. The 28
      observers evaluated the images for approximal carious lesions on a standard
      monitor. All evaluations were made in ambient light below 50 lux. Receiver
      operating characteristic curves were plotted to assess results. The standard
      criterion for healthy or carious lesions was a histological examination of sliced
      teeth. Kappa statistics evaluated intra-observer agreement. For carious lesions
      that had extended into the dentine, significant differences were found between
      (i) Dentists and all other groups, (ii) Dentists and DS-10 (p < 0.01), and (iii)
      Dentists and DS-6 and DHS (p < 0.001). Differences between DS-10 and DHS (p < or
      = 0.05) were also significant. In this study, education level and experience
      clearly influenced the diagnostic accuracy of approximal carious lesions that had
      extended into the dentine on digital radiographs.

PMID- 20701215
TI  - Awareness of toothbrushing and dentifrice habits in regularly dental care
      receiving adults.
AB  - The aim of this study was to investigate toothbrushing and dentifrice habits in a
      Swedish adult population with relatively high caries frequency, which received
      regularly dental care and to evaluate the awareness of their toothbrush
      technique. Sixty adult participants with high caries frequency, 29 woman and 31
      men, answered a self-reporting questionnaire with 42 questions concerning their
      oral care, brushing technique and -habits.The responses were related to their
      clinical behaviour observed during a customary toothbrushing session. Fifty-three
      participants fulfilled both the questionnaire and the clinical observation. Half
      of these used toothpaste containing 1450-1500 ppm fluoride but only one of all
      participants was aware of the fluoride concentration used. The majority used a
      manual toothbrush and 95% brushed their teeth twice a day using 0.9 g toothpaste.
      A wide range of brushing methods and habits was observed. Sixty percent did not
      brush systematically. Spitting of toothpaste-saliva during brushing was performed
      by 60% and after brushing by 15%.The observed brushing times were significantly
      higher than the self reported. The observed brushing times were <1 min: 3.4%, 1-2
      min: 36.7% and >2 min: 47.0%. There was a significant correlation between
      observed brushing time and caries activity. Rinsing with water after brushing was
      performed once (32%) or twice (44%) during the observations. Only 9% rinsed with
      toothpaste slurry after brushing. It can be concluded that the awareness of the
      individual toothbrushing, post-brushing behaviour and the use of fluoride
      toothpaste was non-optimal in the adult participants. Oral health promotion by
      optimalized use of fluoride toothpaste and improved post-brushing behaviour
      should be recommended.

PMID- 20701216
TI  - A randomized prospective clinical evaluation of two desensitizing agents on
      cervical dentine sensitivity. A pilot study.
AB  - The aim of this prospective clinical pilot study was to evaluate the pain
      alleviation effectiveness of two desensitizing agents (VivaSens and Seal&Protect)
      on 30 patients suffering from cervical dentine sensitivity (CDS) over a six month
      period. Analysis of possible differences in pain alleviation effect between the
      agents and over time was performed. Further,the experienced pain was registered
      in a questionnaire regarding to what extent the treatment improved oral
      health/life quality among the patients. The patients (23 female, 7 male) were
      randomly divided into two groups. Each group was treated with one of the two
      desensitizing agents. Sensitivity measurements were recorded before treatment
      (baseline) and after treatment at time points of one week and six months. The
      patients were asked to rate the sensitivity experienced in the area during air
      stimulation by marking on a Visual Analogue Scale (VAS). At six months, 27
      patients (90%) had completed the clinical trial. The results showed that a
      significant reduction of CDS was achieved by using VivaSens or Seal&Protect after
      both one week and six months. However, there were no differences found on
      treatment effects between the two desensitizing agents. The results from the
      questionnaire showed that the patients experienced improved oral health/life
      quality when comparing the status before and after treatment (0.000 < or = p < or
      = 0.0021) and there were no statistically significant difference in treatment
      effects between the products. In conclusion, both desensitizing agents were
      effective in relieving cervical dentin hypersensitivity during the time course of
      the study as evaluated both by air stimulation and a questionnaire related to
      oral health/quality of life status.

PMID- 20701217
TI  - Socio-economic and lifestyle factors in relation to priority of dental care in a
      Swedish adolescent population.
AB  - The aim of this epidemiological survey was to describe and analyze oral health
      habits and life-style factors in relation to the priority of regular dental care
      in 19-year-old individuals with specific reference to gender, residential area
      and socio-economic grouping. The data were generated from a randomized sample of
      758 (63%) individuals in three residential areas in Western Sweden (two rural,
      one urban) who answered a set of questionnaires prior to a dental examination.
      The analysis revealed that males had significantly less favourable oral health
      habits than females. Forty-one % of the males and 30% of the females did not plan
      regular dental visits after the age of 20 when they will be charged for the care
      (p = 0.002). There were no statistically significant differences in oral health
      habits and dental care priorities with regard to residential areas and socio
      economic groups. In a multivariate model, three significant factors for the
      probability of "not planning for future regular dental visits" were identified:
      toothbrushing less than twice daily (OR 1.94; 95% CI 1.28-2.94), smoking (OR
      1.68; 95% CI 1.10-2.56) and male gender (OR 1.54; 95% CI 1.05-2.24). The findings
      emphasize the need for promotion of favourable oral health habits and smoking
      prevention among adolescents. There is also a need for dental personnel to
      recognize differences with regard to oral health-related attitudes and behaviours
      between males and females.

PMID- 20701218
TI  - Self-perceived orthodontic treatment need and prevalence of malocclusion in 18-
      and 19-year-olds in Sweden with different geographic origin.
AB  - Orthodontic treatment need and demand in 19-year-olds in Sweden has not
      previously been analysed in relation to geographic origin. The aim of this follow
      up study was to examine the prevalence of self-perceived treatment need,
      malocclusion, earlier orthodontic treatment, self-perceived dental aesthetics and
      prevalence of symptoms indicative oftemporomandibular disorders in 18-19 year
      olds and to analyze any differences between native born and immigrants. Body
      esteem and psychological wellbeing were also evaluated. The subjects, n=316, were
      grouped according to family origin: Group A: both parents born in Sweden (98
      girls, 80 boys); Group B:the subject or at least one parent born in Eastern
      /South Eastern Europe (24 girls, 26 boys) and Group C: Asia (44 girls, 44 boys).
      Two hundered and sixty-eight participants presented for clinical examination and
      answered the full questionnaire, and 48 who rejected clinical examination,were
      interviewed by telephone using selected questions from a questionnaire. The
      results show that adolescents of Asian origin had a higher self-perceived
      treatment need than adolescents of Swedish origin. There were negligible inter
      group differences with respect to frequency of malocclusion. Forty-four per cent
      of all participants had previously undergone orthodontic treatment, significantly
      more Swedish than Asian subjects. Dissatisfaction with dental aesthetics was
      attributed primarily to tooth colour (38 per cent) and irregular anterior teeth
      (34 per cent). Adolescents of Asian origin had a higher frequency of headache
      than those of Eastern/South Eastern European origin. Compared to boys, girls had
      a higher self-perceived treatment need, a higher frequency of headache and TMD
      and were more concerned about body appearance. Psychological wellbeing was
      reduced in nearly one quarter of the participants, predominantly girls: girls of
      Asian origin had the highest frequency. No association was found between self
      perceived orthodontic treatment need and psychological wellbeing.

PMID- 20701219
TI  - Self-perceived oral health among 65 and 75 year olds in two Swedish counties.
AB  - The aim of this study was to investigate self-perceived oral health in two
      elderly populations, age's 65 and 75 years, and its relation to background
      factors, socioeconomic, individual, and dental health service system factors.
      Another purpose was to investigate if there were any differences in these
      respects, between the two age groups, born in 1932 or 1942. In two counties in
      Sweden, Orebro and Ostergotland, all persons born in 1942 have been surveyed by
      mail every fifth year since 1992. In the year 2007 all persons born in 1932 were
      also surveyed using the same questionnaire. Those born in 1932 consisted of 3735
      persons and those born in 1942 6078 persons. From an outline of a general model
      of inequalities in oral health data were analyzed with descriptive statistics and
      contingency tables with chi2 analysis. Multivariable analysis was performed by
      using multiple regression analysis. Factors related to self-perceived oral health
      were age group, social network, ethnicity, education, general health,tobacco
      habits, oral hygiene routines, dental visit habits and cost for care. The self
      perceived oral health was overall rather high, especially in view of the studied
      ages, although it was worse for those of age 75. Socio-economic factors, dental
      health service system as well as individual lifestyle factors affected self
      perceived oral health. To have a satisfying dental appearance, in the aspect of
      howyou are judged by other people, was important for these age groups. This
      presents a challenge for dental health planners especially since the proportion
      of older age groups are growing.

PMID- 20701220
TI  - In memory of Vincenzo Cuomo; medical doctor and man of letters on the Isle of
      Capri, crossroads of Europe. Introduction.

PMID- 20701221
TI  - [Vincenzo Cuomo, the island's doctor].

PMID- 20701222
TI  - [Ethical decalogue of Vincenzo Cuomo].

PMID- 20701223
TI  - [Vincenzo Cuomo, health officer and general practitioner on the Isle of Capri].
AB  - We provide a broad review of the scientific output of Vincenzo Cuomo, general
      practitioner and health officer on the Isle of Capri. As well as his work as a
      doctor he was a close observer of the environment and in particular of the
      island's splendid climate and its benefits not only for the local population in
      general but also for visitors from northern Europe's colder climes. These mainly
      included tuberculosis sufferers in search of the beneficial effects of the
      Mediterranean climate, as well as those suffering from asthma and chronic
      bronchitis. Vincenzo Cuomo understood the beneficial effects of the island's
      climate and campaigned successfully to have the island formally recognized as a
      major health resort. To add scientific rigour to his observations, he installed a
      fully operational meteorological station at the top of his villa, supplying data
      as part of Italy's network of meteorological and climatological stations over
      some 50 years. Given his contribution to science and medicine, we believe it
      appropriate to consider Vincenzo Cuomo a precursor of modern clinical
      climatology.

PMID- 20701224
TI  - [Vincenzo Cuomo, pioneer in thalassotherapy].
AB  - Thermal Medicine is now well integrated with other therapies such as
      pharmacotherapy, surgery, physiotherapy, radiotherapy and so on, in the
      prevention, cure and rehabilitation of many diseases. The methodology of thermal
      treatments, now recognized as bona fide therapies with their specific
      indications, adverse side effects, dosages, applications and administration
      times, are classified into mineral baths, mudcures and grotto treatments.
      Thalassotherapy is a therapy that is linked to the sea and is one of the most
      important of the climatotherapeutic methods. It constitutes a complex of
      therapeutic effects derived from the meteorological and telluric factors
      characterising a given climate. Thalassotherapy deals with the therapeutic
      effects conferred by periods of time spent by the sea, including the modes of
      action of marine agents, and strives to determine their limitations and in what
      circumstances a sojourn by the sea can provide effective health benefits.
      Thalassotherapy is affected by three kinds of main factors: climatotherapeutic
      factors, eliotherapeutic factors and balneotherapeutic factors. Refraining from
      normal daily activities and a rigorous observance of general hygiene, and diet in
      particular must also always be observed.

PMID- 20701225
TI  - [GILZ (glucocorticoid-induced leucine zipper), a mediator of the anti
      inflammatory and immunosuppressive activity of glucocorticoids].
AB  - Glucocorticoids (GCs) are widely used in therapy as anti-inflammatory and
      immunosuppressive drugs. Their effects are the result of a number of genomic and
      non-genomic mechanisms including regulation of gene transcription. In fact, GCs
      through interaction with the glucocorticoid receptor (GR) regulate transcription
      of a number of target genes. Induction and/or inhibition of gene expression are
      responsible for the therapeutic effects of GC as well of unwanted side effects
      that can limit their therapeutic use. Dissecting the molecular mechanisms
      responsible for beneficial and/or detrimental actions of GC is an important
      challenge in basic research. In particular, a critical issue is to establish how
      a single gene might eventually be linked to a specific GC-induced effect. We
      identified GILZ (glucocorticoid-induced leucine zipper), a gene rapidly activated
      by dexamethasone, during studies aimed at characterizing gene(s) activated by
      GCs. The first experimental evidence indicating GILZ as a player in the GC
      induced immunomodulation comes from observation that GILZ up-regulation in
      Tlymphocytes inhibits anti-CD3-induced activation/proliferation and apoptotic
      cell death. We then found that GILZ interacts with and inhibits NF-icB.
      Subsequently, this observation has been confirmed in many other laboratories and
      other GILZ targets have been identified, including AP-1, Raf-1, and Ras, all
      involved in GC effects. Notably, GILZ inhibition by silencing counters the anti
      proliferative activity of dexamethasone and reduces GC-mediated inhibition of COX
      2 expression. All these effects suggest GILZ as a mediator of the anti
      inflammatory/immunosuppressive activity of GCs.

PMID- 20701226
TI  - [The Society of Nurses supports the increase in subscription fees and closes
      ranks around their president].

PMID- 20701227
TI  - [Management of video game addictions].

PMID- 20701228
TI  - [Prevention of excessive video gaming in school milieu].

PMID- 20701229
TI  - [Dependence on games of chance and gambling].

PMID- 20701230
TI  - [Nursing care of sexual cyberaddiction].

PMID- 20701231
TI  - [Addiction and new forms of virtual communication].

PMID- 20701233
TI  - [School nursing, a daily challenge].

PMID- 20701234
TI  - [Standardization and evaluation of the patient's record].

PMID- 20701235
TI  - [Fibromyalgia syndrome].

PMID- 20701236
TI  - [Education in analysis of an emergency professional situation].

PMID- 20701237
TI  - [Care and observation of a patient having a coloscopy].

PMID- 20701238
TI  - [Anne Carrel (1877-1968)].

PMID- 20701239
TI  - [Duloxetine].

PMID- 20701240
TI  - [It's bad to have lead in the head!].

PMID- 20701241
TI  - Household use of solid fuels and high-temperature frying.

PMID- 20701242
TI  - A QM/QM multilayer composite methodology: The ONIOM correlation consistent
      composite approach (ONIOM-ccCA).
AB  - A QM/QM approach incorporating the correlation consistent composite approach
      (ccCA) into the ONIOM multilayer methodology has been implemented. This new
      multilayer composite scheme, ONIOM-ccCA, enables the accurate prediction of
      thermochemical properties for systems containing dozens-and potentially hundreds
      of atoms. ONIOM-ccCA is used to predict the C-H bond dissociation energies of 18
      anthracene and fluorene analogues, containing up to 43 atoms, to within 1.2 kcal
      mol(-1) of experimental values. Several density functional and basis set
      combinations are evaluated for use as the low level QM layer. The mean absolute
      deviation (1.2 kcal mol(-1)) using the most accurate ONIOM-ccCA method,
      ccCA:B3LYP/cc-pVTZ, is significantly lower than that of an earlier reported
      multilayer composite scheme [2.4 kcal mol(-1), Li, M.-J.; Liu, L.; Fu, Y.; Guo,
      Q.-X. J. Phys. Chem. B, 2005, 109, 13818]. Thus, through use of ONIOM-ccCA,
      accurate thermochemical calculations are now feasible for sizable molecular
      systems of chemical or biological interest.

PMID- 20701244
TI  - Development and validation of a liquid chromatography-electrospray ionization
      time-of-flight mass spectrometry method for induced changes in Nicotiana
      attenuata leaves during simulated herbivory.
AB  - A liquid chromatography-electrospray ionization-time-of-flight mass spectrometry
      (HPLC/ESI-TOF-MS) procedure was developed to characterize changes induced in
      Nicotiana attenuata leaves 1 h and 5 days after wounding and application of
      Manduca sexta elicitors. The constancy of the measurement conditions was first
      confirmed for 22 selected analytes spanning the entire chromatogram. Using the
      Profile Analysis software, we extracted 367 buckets, which were analyzed by
      principal component analysis and two-factorial ANOVA. One hundred seventy-three
      buckets were found to be statistically regulated, 128 due to time effects, and 85
      due to treatment effects. In vivo 15N-isotope labeling was used to facilitate the
      annotation and the interpretation of the fragmentation pattern of nitrogen
      containing metabolites, and a correlation analysis was performed to test
      mathematical relationships existing among potential in-source fragments.
      Additionally, tandem MS measurements of the most regulated ions are presented.
      Altogether, this study defines a framework for the mining and annotation of major
      herbivory-elicited changes in Nicotiana attenuata.

PMID- 20701245
TI  - Effect of pulsed electric fields treatment and mash size on extraction and
      composition of apple juices.
AB  - This study explored the effect of pulsed electric field (PEF) treatment (E=450
      V/cm; tt=10 ms; E<3 kJ/kg) and apple mash size on juice yield, polyphenolic
      compounds, sugars, and malic acid. Juice yield increased significantly after PEF
      treatment of large mash (Y=71.4%) and remained higher than the juice yield
      obtained for a control small mash (45.6%). The acid sweet balance was not altered
      by PEF. A correlation was established between the decrease of light absorbance
      (control: 1.43; treated: 1.10) and the decline of native polyphenols yield due to
      PEF treatment (control: 9.6%; treated: 5.9% for small mash). An enhanced
      oxidation of phenolic compounds in cells due to electroporation of the inner cell
      membrane and the adsorption of the oxidized products on the mash may explain both
      the lower light absorbance and the lower native polyphenol concentration.

PMID- 20701246
TI  - Antioxidant characterization of native monofloral Cuban honeys.
AB  - Five typical Cuban monofloral honeys were analyzed for their in vitro total
      antioxidant capacity (TAC), phenolic compounds, and ascorbic acid content.
      Identification and quantification of phenolics were carried out by HPLC-DAD
      ESI/MS. Fourteen phenolic compounds could be identified (eight phenolic acids and
      six flavonoids), including three glycosylated derivatives. Similar contents of
      total phenolics were found in the different honeys, although they differed in
      their qualitative profiles. A significant (positive) correlation was found
      between the results of TAC obtained by parallel FIA-ABTS system and ORAC assay
      (r=0.9565, p<0.001). Similar correlations were also established between total
      phenolics and TAC, determined by either the ORAC (r=0.9633; p<or=0.001) or the
      TEAC assay (r=0.9582; p<or=0.001). Honeys were fractionated by solid-phase
      extraction into four fractions, and the relative contribution of each fraction to
      TAC was calculated. Phenolic compounds were significant contributors to the
      antioxidant capacity of the honeys, but they were not uniquely responsible for
      it. The antioxidant activity appeared to be a result of the combined activity of
      a range of compounds including phenolics and other minor components. Ascorbic
      acid was not detected.

PMID- 20701247
TI  - Theoretical investigations on the formation and dehydrogenation reaction pathways
      of H(NH2BH2)(n)H (n = 1-4) oligomers: importance of dihydrogen interactions.
AB  - The H(NH(2)BH(2))(n)H oligomers are possible products from dehydrogenation of
      ammonia borane (NH(3)BH(3)) and ammonium borohydride (NH(4)BH(4)), which belong
      to a class of boron-nitrogen-hydrogen (BNH(x)) compounds that are promising
      materials for chemical hydrogen storage. Understanding the kinetics and reaction
      pathways of formation of these oligomers and their further dehydrogenation is
      essential for developing BNH(x)-based hydrogen storage materials. We have
      performed computational modeling using density functional theory (DFT), ab initio
      wave function theory, and Car-Parrinello molecular dynamics (CPMD) simulations on
      the energetics and formation pathways for the H(NH(2)BH(2))(n)H (n = 1-4)
      oligomers, polyaminoborane (PAB), from NH(3)BH(3) monomers and the subsequent
      dehydrogenation steps to form polyiminoborane (PIB). Through computational
      transition state searches and evaluation of the intrinsic reaction coordinates,
      we have investigated the B-N bond cleavage, the reactions of NH(3)BH(3) molecule
      with intermediates, dihydrogen release through intra- and intermolecular hydrogen
      transfer, dehydrocoupling/cyclization of the oligomers, and the dimerization of
      NH(3)BH(3) molecules. We find that the formation of H(NH(2)BH(2))(n+1)H oligomers
      occurs first through reactions of the H(NH(2)BH(2))(n)H oligomers with BH(3)
      followed by reactions with NH(3) and the release of H(2), where the BH(3) and
      NH(3) intermediates are formed through dissociation of NH(3)BH(3). We also find
      that the dimerization of the NH(3)BH(3) molecules to form cyclic c
      (NH(2)BH(2))(2) is slightly exothermic, with an unexpected transition state that
      leads to the simultaneous release of two H(2) molecules. The dehydrogenations of
      the oligomers are also exothermic, typically by less than 10 kcal/(mol of H(2)),
      with the largest exothermicity for n = 3. The transition state search shows that
      the one-step direct dehydrocoupling cyclization of the oligomers is not a favored
      pathway because of high activation barriers. The dihydrogen bonding, in which
      protic (H(N)) hydrogens interact with hydridic (H(B)) hydrogens, plays a vital
      role in stabilizing different structures of the reactants, transition states, and
      products. The dihydrogen interaction (DHI) within the R-BH(2)(eta(2)-H(2)) moiety
      accounts for both the formation mechanisms of the oligomers and for the
      dehydrogenation of ammonia borane.

PMID- 20701248
TI  - BaGa2Pn2 (Pn = P, As): new semiconducting phosphides and arsenides with layered
      structures.
AB  - Reported are the synthesis, the structural characterization, and the electronic
      band structures of two new Zintl phases: BaGa2P2 and BaGa2As2. Both compounds are
      isoelectronic and isotypic and crystallize in a monoclinic system with a new
      structure type (Pearson symbol mP20). The structures have been established by
      single-crystal X-ray diffraction, space group P2(1)/c (Z = 4), with lattice
      parameters as follows: a = 7.3363(13)/7.495(5) A; b = 9.6648(17)/9.901(6) A; c =
      7.4261(13)/7.643(5) A; beta = 115.373(2) degrees/115.381(8) degrees for
      BaGa2P2/BaGa2As2, respectively. The atomic arrangements in both cases are devoid
      of disorder and are best rationalized as polyanionic layers,
      (infinity)(2)[Ga2Pn2]2- (Pn = P, As), with Ba2+ cations separating them. The
      layers, in turn, can be viewed as the result of condensation of Ga2Pn6 units,
      which are isosteric with the ethane molecule in its staggered conformation.
      Structural parallels with other known Zintl phases are presented. The electronic
      structures, computed using the tight-binding linear muffin-tin orbital methods
      (TB-LMTO), are discussed as well.

PMID- 20701249
TI  - Octapod-shaped colloidal nanocrystals of cadmium chalcogenides via "one-pot"
      cation exchange and seeded growth.
AB  - The growth behavior of cadmium chalcogenides (CdE = CdS, CdSe, and CdTe) on
      sphalerite Cu(2-x)Se nanocrystals (size range 10-15 nm) is studied. Due to the
      capability of Cu(2-x)Se to undergo a fast and quantitative cation exchange
      reaction in the presence of excessive Cd(2+) ions, no Cu(2-x)Se/CdE
      heterostructures are obtained and instead branched CdSe/CdE nanocrystals are
      built which consist of a sphalerite CdSe core and wurtzite CdE arms. While CdTe
      growth yields multiarmed structures with overall tetrahedral symmetry, CdS and
      CdSe arm growth leads to octapod-shaped nanocrystals. These results differ
      significantly from literature findings about the growth of CdE on sphalerite CdSe
      particles, which until now had always yielded tetrapod-shaped nanocrystals.

PMID- 20701250
TI  - Experimental evidence for the nanocage effect in catalysis with hollow
      nanoparticles.
AB  - Five different hollow cubic nanoparticles with wall length of 75 nm were
      synthesized from platinum and/or palladium elements. The five nanocatalysts are
      pure platinum nanocages (PtNCs), pure palladium nanocages (PdNCs), Pt/Pd hollow
      shell-shell nanocages (NCs) (where Pd is defined as the inner shell around the
      cavity), Pd/Pt shell-shell NCs, and Pt-Pd alloy NCs. These are used to catalyze
      the reduction of 4-nitrophenol with sodium borohydride. The kinetic parameters
      (rate constants, activation energies, frequency factors, and entropies of
      activation) of each shell/shell NCs are found to be comparable to that of pure
      metal NCs made of the same metal coating the cavity in the shell-shell NCs. These
      results strongly suggest that the catalytic reaction takes place inside the
      cavity of the hollow nanoparticles. Because of the nanoreactor confinement effect
      of the hollow nanocatalysts, the frequency factors obtained from the Arrhenius
      plots are found to be the highest ever reported for this reduction reaction. This
      is the reason for enhanced rate of this reaction inside the cavity. The
      importance of mechanism of the homogeneous and the heterogeneous nanocatalytic
      reactions occurring on the external surface of a solid nanoparticle are
      contrasted with those occurring on the nanocavity surface.

PMID- 20701266
TI  - Direct derivatization and rapid GC-MS screening of nerve agent markers in aqueous
      samples.
AB  - A rapid screening and identification method based on derivatization and gas
      chromatography mass spectrometry (GC-MS) has been developed for the detection of
      alkylphosphonic acids (APAs), the degradation products of organophosphorus nerve
      agents. The novel method described involves rapid (5 min) and direct
      derivatization of 25 microL aqueous sample using highly fluorinated
      phenyldiazomethane reagents (e.g., 1-(diazomethyl)-3,5
      bis(trifluoromethyl)benzene). The APA derivatives are then screened by GC-MS
      negative ion chemical ionization (NICI) and identified by electron ionization
      (EI) mode. The conditions for the derivatization were optimized using statistical
      experimental design and multivariate data analysis. Method robustness was
      evaluated using aqueous samples from an official OPCW Proficiency Test and all
      APAs present in the sample were conclusively identified. Limits of detection for
      rapid screening using SIM NICI were between 5 and 10 ng/mL APA in aqueous sample,
      and for identification using full scan EI 100 ng/mL.

PMID- 20701267
TI  - Magnetic nanochains of FeNi3 prepared by a template-free microwave-hydrothermal
      method.
AB  - Magnetic FeNi3 nanochains were synthesized by reducing iron(III) acetylacetonate
      and nickel(II) acetylacetonate with hydrazine in ethylene glycol solution without
      any template under a rapid and economical microwave irradiation. The morphology
      and composition of the as-prepared products were characterized by field-emission
      scanning electron microscopy (FESEM), transmission electron microscopy (TEM), X
      ray diffraction (XRD), and elemental mapping. The size of the aligned nanospheres
      in the magnetic FeNi3 chains could be adjusted from 150 to 550 nm by increasing
      the amounts of the precursors. The length of the nanochain is about several tens
      of micrometers. The ratio of the precursors plays an important role in the
      formation of FeNi3 nanostructures. Magnetic measurement reveals that the FeNi3
      nanochains show enhanced coercivity and saturation magnetization. The formation
      mechanism of the product is discussed. Toxicity tests of FeNi3 nanochains show
      that the as-prepared nanochains are nontoxic to zebrafish larvae. In vitro
      magnetic resonance imaging (MRI) confirms the effectiveness of the FeNi3
      nanochains as sensitive MRI probes.

PMID- 20701268
TI  - Nonspecific DNA binding and coordination of the first two steps of base excision
      repair.
AB  - The base excision repair (BER) pathway repairs a wide variety of damaged
      nucleobases in DNA. This pathway is initiated by a DNA repair glycosylase, which
      locates the site of damage and catalyzes the excision of the damaged nucleobase.
      The resulting abasic site is further processed by apurinic/apyrimidinic site
      endonuclease 1 (APE1) to create a single-strand nick with the 3'-hydroxyl that
      serves as a primer for DNA repair synthesis. Because an abasic site is highly
      mutagenic, it is critical that the steps of the BER pathway be coordinated. Most
      human glycosylases bind tightly to their abasic product. APE1 displaces the bound
      glycosylase, thereby stimulating multiple-turnover base excision. It has been
      proposed that direct protein-protein interactions are involved in the stimulation
      by APE1, but no common interaction motifs have been identified among the
      glycosylases that are stimulated by APE1. We characterized the APE1 stimulation
      of alkyladenine DNA glycosylase (AAG) using a variety of symmetric and asymmetric
      lesion-containing oligonucleotides. Efficient stimulation of a wide variety of
      substrates favors a model in which both AAG and APE1 can simultaneously bind to
      DNA but may not interact directly. Rather, nonspecific DNA binding by both AAG
      and APE1 enables APE1 to replace AAG at the abasic site. AAG is not displaced
      into solution but remains bound to an adjacent undamaged site. We propose that
      nonspecific DNA binding interactions allow transient exposure of the abasic site
      so that it can be captured by APE1.

PMID- 20701269
TI  - Intensity borrowing via excitonic couplings among soret and Q(y) transitions of
      bacteriochlorophylls in the pigment aggregates of chlorosomes, the light
      harvesting antennae of green sulfur bacteria.
AB  - Model calculations of linear dichroism (LD) and circular dichroism (CD) spectra
      were conducted for the chlorosomes of green sulfur bacteria, Chlorobium
      phaeobacteroides and Chlorobium tepidum, on the basis of the theory of
      delocalized exciton. The chlorosomes of Chl. phaeobacteroides and Chl. tepidum
      contain bacteriochlorophylls (BChls) e and c as the major light-harvesting
      pigments, respectively. The excitonic couplings among the Soret and Q(y)
      transitions were considered on the basis of the "rodlike" structural model for
      the pigment self-aggregates in a chlorosome. Trial simulations were conducted by
      assuming the B(x) and B(y) transition-dipole vectors to be parallel to the
      molecular x- and y-axes, respectively. The simulation at this stage could nicely
      reproduce the larger splitting of the Soret band and more significant enhancement
      of the Q(y) band upon formation of chlorosome in the BChl e-containing chlorosome
      than in the BChl c-containing one. Intensity borrowing was indicated to be the
      key mechanism inducing the enhancement of the Q(y) band in the BChl e-containing
      chlorosomes. However, the simulated LD and CD spectra in the Soret region showed
      qualitative disagreement from the observed ones. To resolve the deviations, the
      directions of the B(x) and B(y) transition-dipole vectors and the orientations of
      the molecular planes of BChls were adjusted in the next stage. The fine-tuning of
      these parameters resulted in a striking agreement between the observed and
      simulated CD and LD spectra over the whole spectral range studied. The best fit
      was obtained when the B(x) and B(y) transition-dipole vectors were assumed to be
      rotated 25 degrees clockwise from the molecular x- and y-axes and the molecular
      planes in the pigment aggregate were tilted 5 degrees from that assumed in the
      original model without alteration in the direction of the molecular y-axis. The
      calculated spectral profiles were affected little by the change in the curvatures
      of the rod surface, showing that the optical spectra of chlorosomes were
      determined essentially by the local pigment arrangement, but not by the higher
      order structure, of the aggregate.

PMID- 20701270
TI  - Phase-resolved mapping of the near-field vector and polarization state in
      nanoscale antenna gaps.
AB  - We demonstrate that the local near-field vector and polarization state on planar
      antenna structures and in nanoscale antenna gaps can be determined by scattering
      type near-field optical microscopy (s-SNOM). The near-field vector is
      reconstructed from the amplitude and phase images of the in- and out-of-plane
      near-field components obtained by polarization-resolved interferometric
      detection. Experiments with a mid-infrared inverse bowtie antenna yield a
      vectorial near-field distribution with unprecedented resolution of about 10 nm
      and in excellent agreement with numerical simulations. Furthermore, we provide
      first direct experimental evidence that the nanoscale confined and strongly
      enhanced fields at the antenna gap are linearly polarized. s-SNOM vector-field
      mapping paves the way to a full near-field characterization of nanophotonic
      structures in the broad spectral range between visible and terahertz frequencies,
      which is essential for future development and quality control of metamaterials,
      optical sensors, and waveguides.

PMID- 20701271
TI  - Asymmetric alkyl-alkyl cross-couplings of unactivated secondary alkyl
      electrophiles: stereoconvergent Suzuki reactions of racemic acylated halohydrins.
AB  - A method for asymmetric alkyl-alkyl Suzuki reactions of unactivated secondary
      alkyl electrophiles, specifically, cross-couplings of racemic acylated
      halohydrins with alkylborane reagents, has been developed. A range of protected
      bromohydrins, as well as a protected chlorohydrin and a homologated bromohydrin,
      are coupled in good ee by a catalyst derived from commercially available
      components.

PMID- 20701273
TI  - Ozonolysis of maleic acid aerosols: effect upon aerosol hygroscopicity, phase and
      mass.
AB  - The hygroscopicity and mass loss of aerosols initially composed of maleic acid
      have been investigated before and after reaction with ozone. The phase of the
      aerosol, solid or aqueous, during the reaction with ozone strongly affects the
      composition of the processed aerosol. Furthermore the loss of aerosol mass, via
      the production of volatile ozonolysis products, does not occur until the
      processed aerosol has existed as an aqueous phase aerosol. The loss rate of the
      aerosol mass appears to follow unimolecular first order kinetics which is
      consistent with the rate determining step being the cleavage of a weak
      hydroperoxide, or peroxide, bond (approximately 104 kJ mol(-1)). This speculative
      rate determining step, which is not based on chemical analysis, is possibly a
      universal feature in the ozonolysis of organic aerosol containing the alkene
      functionality.

PMID- 20701272
TI  - 4-Quinolones: smart phones of the microbial world.

PMID- 20701274
TI  - Switch of regioselectivity in palladium-catalyzed silaboration of terminal
      alkynes by ligand-dependent control of reductive elimination.
AB  - The regioselectivity in the addition of silylboronic esters to terminal alkynes
      can be switched by the choice of phosphorus ligands on the palladium catalysts.
      The silaboration proceeds with normal regioselectivity in the presence of (eta(3)
      C(3)H(5))Pd(PPh(3))Cl (1.0 mol %) to give 1-boryl-2-silyl-1-alkenes in high
      yields. In sharp contrast, selective formation of the inverse regioisomers, 2
      boryl-1-silyl-1-alkenes, takes place when the reaction is carried out with a
      palladium catalyst bearing P(t-Bu)(2)(biphenyl-2-yl). A reaction mechanism for
      the change of regioselectivity that involves reversible insertion/beta-boryl
      elimination steps is proposed.

PMID- 20701275
TI  - Bioaccumulation of organic contaminants in humans: a multimedia perspective and
      the importance of biotransformation.
AB  - Bioaccumulation is an important component of the exposure hazard assessment and
      risk assessment of organic chemicals. Screening criteria for chemical hazard used
      in national and international regulations are based on the paradigm that
      partitioning properties are the primary chemical determinants of bioaccumulation.
      We use a holistic multimedia perspective to evaluate the partitioning property
      paradigm with respect to assessing human bioaccumulation. Multimedia
      bioaccumulation factors (mmBAFs) for humans were modeled for hypothetical
      chemicals with a wide range of physical-chemical properties. Varying partitioning
      properties over 12 orders of magnitude (a plausible range for nonionizing
      organics) resulted in only modest changes in mmBAFs (a factor of ~ 10) for all
      but very volatile or hydrophilic chemicals. In contrast, varying
      biotransformation rate constants over 6 orders of magnitude resulted in
      substantial differences in mmBAFs (greater than a factor of 10(9)). Our model
      results are supported by empirical observations of well characterized pollutants,
      which demonstrate that chemicals with similar partitioning properties can have
      very different bioaccumulation behavior. Susceptibility to biotransformation
      clearly determines bioaccumulation in humans for many chemicals. We conclude that
      a holistic multimedia perspective for bioaccumulation assessment is necessary to
      develop regulations, criteria, and policies that are protective of human health
      and the environment.

PMID- 20701276
TI  - Reaction of Ru(II) diazafluorenone compound with nanocrystalline TiO2 thin film.
AB  - The Ru(II) compounds [Ru(bpy)(2)(mcbH)](2+) and [Ru(bpy)(2)(dafo)](2+), bpy is
      2,2'-bipyridine where mcbH is 3-(CO(2)H)-2,2'-bipyridine and dafo is 4,5
      diazafluoren-9-one, were synthesized, characterized, and anchored to
      nanocrystalline mesoporous TiO(2) thin films for excited state and interfacial
      electron transfer studies. X-ray crystallographic studies of
      [Ru(bpy)(2)(mcbH)](PF(6))(Cl) revealed a long Ru-N distance to the unsubstituted
      pyridine ligand of mcbH. Reaction of [Ru(bpy)(2)(dafo)](2+) with TiO(2) thin
      films resulted in interfacial chemistry. The IR, (1)H NMR, UV-vis, and
      photoluminescence spectral data indicated a room-temperature ring-opening
      reaction of the dafo ligand of [Ru(bpy)(2)(dafo)](2+) that ultimately yielded a
      carboxylate group in the 3-position of bipyridine anchored to TiO(2). Comparative
      reactions of [Ru(bpy)(2)(mcbH)](2+) with TiO(2) were performed and support this
      conclusion. In regenerative photoelectrochemical solar cells with 0.5 M LiI/0.05
      M I(2) in acetonitrile, photocurrent action spectra were observed for both
      sensitized materials. The incident photon-to-current efficiency (IPCE) was
      significantly lower for Ru(bpy)(2)(dafo)/TiO(2), behavior attributed to a lower
      excited-state injection yield.

PMID- 20701277
TI  - Enantioselective organocatalytic C-H bond functionalization via tandem 1,5
      hydride transfer/ring closure: asymmetric synthesis of tetrahydroquinolines.
AB  - The first organocatalytic enantioselective intramolecular 1,5-hydride
      transfer/ring closure reaction is described. This redox neutral reaction cascade
      allows for the efficient formation of ring-fused tetrahydroquinolines in high
      enantioselectivities.

PMID- 20701278
TI  - An improved method for estimating in situ sampling rates of nonpolar passive
      samplers.
AB  - The quality of passive sampling methods for measuring concentrations of dissolved
      hydrophobic contaminants relies on accurate knowledge of in situ sampling rates.
      In currently used methods for estimating these sampling rates from the
      dissipation rates of performance reference compounds (PRCs), the PRCs that show
      either insignificant or complete dissipation are ignored. We explored the merits
      of nonlinear least-squares (NLS) methods for estimating sampling rates, aiming to
      retain the information stored in PRC data that is neglected in the traditional
      methods. To this end, we examined the error structure of weighted NLS, unweighted
      NLS, and the traditional methods, using model simulations. The results show that
      sampling rates are best estimated using unweighted NLS. Uncertainties in the
      sampler-water partition coefficients may result in biased estimates that only
      weakly depend on the number of PRCs being used. The major advantage of unweighted
      NLS over the traditional method is that sampling rate estimates and uncertainties
      are available where the traditional method fails, and that the variability of
      sampling rate estimates is smaller.

PMID- 20701280
TI  - High-level exposure to lithium, boron, cesium, and arsenic via drinking water in
      the Andes of northern Argentina.
AB  - Elevated concentrations of arsenic in drinking water are common worldwide,
      however, little is known about the presence of other potentially toxic elements.
      We analyzed 31 different elements in drinking water collected in San Antonio de
      los Cobres and five surrounding Andean villages in Argentina, and in urine of the
      inhabitants, using ICP-MS. Besides confirmation of elevated arsenic
      concentrations in the drinking water (up to 210 microg/L), we found remarkably
      high concentrations of lithium (highest 1000 microg/L), cesium (320 microg/L),
      rubidium (47 microg/L), and boron (5950 microg/L). Similarly elevated
      concentrations of arsenic, lithium, cesium, and boron were found in urine of the
      studied women (N=198): village median values ranged from 26 to 266 microg/L of
      arsenic, 340 to 4550 microg/L of lithium, 34 to 531 microg/L of cesium, and 2980
      to 16,560 microg/L of boron. There is an apparent risk of toxic effects of long
      term exposure to several of the elements, and studies on associations with
      adverse human health effects are warranted, particularly considering the
      combined, life-long exposure. Because of the observed wide range of
      concentrations, all water sources used for drinking water should be screened for
      a large number of elements; obviously, this applies to all drinking water sources
      globally.

PMID- 20701279
TI  - Redox reactions of the alpha-synuclein-Cu(2+) complex and their effects on
      neuronal cell viability.
AB  - alpha-Synuclein (alpha-syn), a presynaptic protein believed to play an important
      role in neuropathology in Parkinson's disease (PD), is known to bind Cu(2+).
      Cu(2+) has been shown to accelerate the aggregation of alpha-syn to form various
      toxic aggregates in vitro. Copper is also a redox-active metal whose complexes
      with amyloidogenic proteins/peptides have been linked to oxidative stress in
      major neurodegenerative diseases. In this work, the formation of the Cu(2+)
      complex with alpha-syn or with an N-terminal peptide, alpha-syn(1-19), was
      confirmed with electrospray-mass spectrometry (ES-MS). The redox potentials of
      the Cu(2+) complex with alpha-syn (alpha-syn-Cu(2+)) and alpha-syn(1-19) were
      determined to be 0.018 and 0.053 V, respectively. Furthermore, the Cu(2+)
      center(s) can be readily reduced to Cu(+), and possible reactions of alpha-syn
      Cu(2+) with cellular species (e.g., O(2), ascorbic acid, and dopamine) were
      investigated. The occurrence of a redox reaction can be rationalized by comparing
      the redox potential of the alpha-syn-Cu(2+) complex to that of the specific
      cellular species. For example, ascorbic acid can directly reduce alpha-syn-Cu(2+)
      to alpha-syn-Cu(+), setting up a redox cycle in which O(2) is reduced to H(2)O(2)
      and cellular redox species is continuously exhausted. In addition, the H(2)O(2)
      generated was demonstrated to reduce viability of the neuroblastoma SY-HY5Y
      cells. Although our results ruled out the direct oxidation of dopamine by alpha
      syn-Cu(2+), the H(2)O(2) generated in the presence of alpha-syn-Cu(2+) can
      oxidize dopamine. Our results suggest that oxidative stress is at least partially
      responsible for the loss of dopaminergic cells in PD brain and reveal the
      multifaceted role of the alpha-syn-Cu(2+) complex in oxidative stress associated
      with PD symptoms.

PMID- 20701281
TI  - Noninvasive probing of inhibitory effects of cylindrospermopsin and microcystin
      LR using cell-based impedance spectroscopy.
AB  - In an effort to develop a noninvasive method for assessment of cyanobacterial
      toxins in drinking water, plausible cytotoxicity/inhibition of microcystin-LR and
      cylindrospermopsin was evaluated by cell-substrate impedance sensing (ECIS) using
      three different cell lines. Sf9 insect cells were attached to concanavalin A
      coated gold electrodes, whereas Chinese hamster ovary (CHO) and human embryo
      kidney (HEK) cells were attached to a fibronectin or laminin coated gold surface.
      Cytotoxic or inhibitory effects were dependent upon the cell line and the
      extracellular matrix (ECM) coating. Neither toxin exhibited any appreciable
      effect on the insect cells. In contrast, cytotoxicity of cylindrospermopsin on
      CHO cells was attested by both ECIS and viability tests. The half-inhibition
      concentration (ECIS50) of cylindrospermopsin for CHO cells was approximately 2
      microg/mL (ppm) after 20 h of exposure and 4 microg/mL (ppm) after 30 h of
      exposure for a laminin or fibronectin coated surface. ECIS confirmed no
      significant effect of cylindrospermopsin on HEK cells. Microcystin-LR was also
      tested with CHO cells, resulting in an ECIS50 value of approximately 12 microg/mL
      (ppm) after 25 h of exposure for a laminin coated gold surface. The effect of
      microcystin-LR on CHO cells probed by ECIS was inhibitory rather than cytotoxic,
      as confirmed by cell viability assays.

PMID- 20701282
TI  - Reversible magnetism between an antiferromagnet and a ferromagnet related to
      solvation/desolvation in a robust layered [Ru2]2TCNQ charge-transfer system.
AB  - The charge-transfer compound [{Ru(2)(O(2)CPh-o-Cl)(4)}(2)TCNQ(MeO)(2)] x
      CH(2)Cl(2) (1; o-ClPhCO(2)(-) = o-chlorobenzoate; TCNQ(MeO)(2) = 2,5-dimethoxy
      7,7,8,8-tetracyanoquinodimethane) was synthesized from the reaction of the
      neutral precursors [Ru(2)(II,II)(O(2)CPh-o-Cl)(4)] (abbreviated as [Ru(2)(II,II)]
      or [Ru(2)(4+)]) and TCNQ(MeO)(2) in a CH(2)Cl(2)/nitrobenzene solution. The
      structure consists of two-dimensional layers consisting of an infinite array in
      which [Ru(2)(II,II)] units are involved in charge transfer to TCNQ(MeO)(2) to
      give a formal charge of [{Ru(2)(4.5+)}-TCNQ(MeO)(2)(*-)-{Ru(2)(4.5+)}].
      Interstitial CH(2)Cl(2) molecules are located in the void spaces between the
      layers. Strong intralayer magnetic coupling between the units [Ru(2)(II,II)] with
      S = 1 or [Ru(2)(II,III)] with S = 3/2 and TCNQ(MeO)(2)(*-) with S = 1/2, as well
      as long-range ordering due to antiferromagnetic interlayer interactions, was
      observed. An antiferromagnetic ground state exists below T(N) = 75 K, which
      undergoes a metamagnetic transition under applied fields less than 2 T to a field
      induced canted antiferromagnetic state with large coercivities up to H(c) = 1.6 T
      at 1.8 K. Compound 1 gradually loses the interstitial CH(2)Cl(2) molecule at room
      temperature to form a dried sample (1-dry) without loss of crystallinity and
      converts nearly reversibly back to 1 after being exposed to CH(2)Cl(2) vapor for
      72 h (distinguished as 1'). Interestingly, during this process there is no
      significant change in lattice dimensions and bond distances or angles with a
      volume change of only 1.2 vol %. The only discernible difference is
      ordering/disordering of a pendant ligand orientation, but the magnetism is
      dramatically altered to a ferromagnetic state with T(c) approximately 56 K for 1
      dry. The magnetic property changes are gradual and depend on the degree of
      interstitial CH(2)Cl(2) molecule loss with reversibility in the process of going
      between 1 and 1-dry. In addition, in the case of partially desolvated crystals
      that have mixed domains of ferromagnetically and antiferromagnetically ordered
      domains for desolvated and solvated segments, respectively, the complete change
      to ferromagnet can also be triggered by magnetic fields even if the desolvated
      segments are comparatively minor compared to the solvated segments in a crystal.
      Surprisingly, the information of the existence of ferromagnetically ordered
      domains is dynamically recorded in the entire crystal after applying significant
      magnetic fields as if the majority of the antiferromagnetically ordered domains
      for solvated segments were never present.

PMID- 20701283
TI  - Distribution and translocation of selenium from soil to grain and its speciation
      in paddy rice (Oryza sativa L.).
AB  - Selenium, an essential micronutrient for humans, is insufficient in dietary
      intake for millions of people worldwide. Rice as the most popular staple food in
      the world is one of the dominant selenium (Se) sources for people. The
      distribution and translocation of Se from soil to grain were investigated in a Se
      rich environment in this study. The Se levels in soils ranged widely from 0.5 to
      47.7 mg kg(-1). Selenium concentration in rice bran was 1.94 times higher than
      that in corresponding polished rice. The total Se concentrations in the rice
      fractions were in the following order: straw>bran>whole grain>polished rice>husk.
      Significant linear relationships between different rice fractions were observed
      with each other, and Se in the soil has a linear relationship with different rice
      fractions as well. Se concentration in rice can easily be predicted by soil Se
      concentrations or any rice fractions and vice versa according to their linear
      relationships. In all rice samples for Se speciation, SeMet was the major Se
      species, followed by MeSeCys and SeCys. The average percentage for SeMet (82.9%)
      and MeSeCys (6.2%) was similar in the range of total Se from 2.2 to 8.4 mg kg(-1)
      tested. The percentage of SeCys decreased from 6.3 to 2.8%, although its
      concentration elevated with the increase in total Se in rice. This could be due
      to the fact that SeCys is the precursor for the formation of other organic Se
      compounds. The information obtained may have considerable significance for
      assessing translocation and accumulation of Se in plant.

PMID- 20701284
TI  - Efficient characterization of pollutant-emission response under parametric
      uncertainty.
AB  - An essential requirement of modeling for air quality management is to accurately
      simulate the responses of pollutant concentrations to changes in emissions.
      Uncertain model input parameters such as emission rates and reaction rate
      constants lead to uncertainty in model responses. However, traditional methods
      for characterizing parametric uncertainty are exceedingly computationally
      intensive. This paper presents methods for using high-order sensitivity
      coefficients in analytical equations to efficiently represent how the
      responsiveness of pollutants to emission reductions in the underlying
      photochemical model varies with simultaneous perturbations in multiple model
      input parameters. Separate approaches are introduced for characterizing the
      parametric uncertainty of pollutant response to a fixed or a variable amount of
      emission reduction. The approaches are demonstrated for an air pollution episode
      used in recent attainment planning in Georgia. For hypothetical scenarios in
      which domain-wide emission rates and photolysis rates are perturbed
      simultaneously by 50%, the reduced form models yield highly accurate predictions
      of the ozone impacts due to 50% reductions in nitrogen-oxide emissions in Atlanta
      (normalized mean bias 6.0%, normalized mean error 9.7%, R2=0.992) and inorganic
      particulate responses to Atlanta sulfur-dioxide emissions (-2.9% bias, 3.7%
      error, R2=1.000). Similar accuracy is achieved for pollutant responses to power
      plant emission controls.

PMID- 20701285
TI  - Energetic and entropic contributions to self-assembly of binary nanocrystal
      superlattices: temperature as the structure-directing factor.
AB  - We studied the effect of temperature on self-assembly of monodisperse colloidal
      nanocrystals into single-component and binary superlattices. Temperature, which
      serves as a weighting factor for the internal energy (U) and entropy (S)
      contributions to the Helmholtz free energy F = U - TS, allows tailoring relative
      weights of the interparticle interactions and free-volume entropy during the
      formation of nanocrystal superlattices. Temperature also provides a convenient
      tool for directing self-assembly of nanocrystals toward desired superlattice
      structures. We found that temperature strongly affects the structures of binary
      superlattices self-assembled from the mixtures of CdSe + PbS nanocrystals and
      PbSe + Pd nanocrystals. In the former case, small Hamaker constants for CdSe and
      PbS nanocrystals led to a relatively simple phase diagram, including only high
      density NaZn(13)-, AlB(2)-, and NaCl-type binary superlattices. In contrast,
      binary superlattices self-assembled at different temperatures from PbSe and Pd
      nanocrystals showed a number of low-density complex phases stabilized by strong
      local van der Waals interactions between Pd nanocrystals. The structural
      diversity of nanoparticle superlattices is shown to be a result of the
      cooperative effect of the entropy-driven crystallization and the interparticle
      interactions. Both DeltaU and TDeltaS terms associated with the superlattice
      formation should be of the same order of magnitude, with |DeltaU| < |TDeltaS| for
      the assembly of CdSe and PbS nanocrystals and |DeltaU| > |TDeltaS| for the PbSe
      and Pd nanocrystals.

PMID- 20701286
TI  - Hexagonal superlattice of chiral conducting polymers self-assembled by mimicking
      beta-sheet proteins with anisotropic electrical transport.
AB  - An ordered superlattice self-assembled from monodispersed nanostructures can
      exhibit collective effects of its individual building blocks, a desirable
      property that gives rise to potential applications. However, no general method
      for the direct fabrication of superstructures yet exists, especially for
      superlattices that start from rational-designed functional molecules. Noncovalent
      interactions are widely used for the self-assembly of biomolecules in nature,
      such as various superstructures of proteins. Instead of using hydrogen bonds as
      driving force for the self-assembly of beta-sheet structures of peptides, pi-pi
      stacking interactions were used in this study to self-assemble conducting
      polyaniline (PANI) nanostructures and superstructures. Monodispersed crystalline
      PANI nanorices were prepared by using homochiral PANI as building blocks; these
      nanorices can further self-assemble into hexagonal microplates aligned shoulder
      to shoulder. PANI molecules were organized into nanorices via single-handed
      helical pi-pi stacking, in which the molecular plane was normal to the long axis
      of the nanorices. Electrical transport measurements showed the anisotropic
      characteristics of self-assembled nanorices and their superstructures, which were
      due to the directional transport barrier in the nanorices and the structural
      defects at the interfaces between neighboring nanorices. As chiral PANI and
      peptides have similar self-assembly behaviors, the method used in this study is
      greatly expected to be applicable to other chemical and biochemical building
      blocks.

PMID- 20701287
TI  - Photopromoted Ru-catalyzed asymmetric aerobic sulfide oxidation and epoxidation
      using water as a proton transfer mediator.
AB  - Ru(NO)-salen complexes were found to catalyze asymmetric aerobic oxygen atom
      transfer reactions such as sulfide oxidation and epoxidation in the presence of
      water under visible light irradiation at room temperature. Oxidation of sulfides
      including alkyl aryl sulfides and 2-substituted 1,3-dithianes using complex 2 as
      the catalyst proceeded with moderate to high enantioselectivity of up to 98% ee,
      and epoxidation of conjugated olefins using complex 3 as the catalyst proceeded
      with good to high enantioselectivity of 76-92% ee. Unlike biological oxygen atom
      transfer reactions that need a proton and electron transfer system, this aerobic
      oxygen atom transfer reaction requires neither such a system nor a sacrificial
      reductant. Although the mechanism of this oxidation has not been completely
      clarified, some experimental results support the notion that an aqua ligand
      coordinated with the ruthenium ion serves as a proton transfer agent for the
      oxygen activation process, and it is recycled and used as the proton transfer
      mediator during the process. Thus, we have achieved catalytic asymmetric oxygen
      atom transfer reaction using molecular oxygen that can be carried out under
      ambient conditions.

PMID- 20701288
TI  - Efficient delivery of payload into tumor cells in a controlled manner by TAT and
      thiolytic cleavable PEG co-modified liposomes.
AB  - Recently, PEGylation has been extensively employed to increase the circulation
      time of liposomes and enhance their accumulation in tumor tissue via the enhanced
      permeability and retention (EPR) effect; however, poly(ethylene glycol) (PEG) is
      unfavorable for the uptake of liposomes by tumor cells because of its steric
      hindrance. In this study, thiolytic cleavable PEG modified liposomes were used to
      solve this dilemma. Before arrival at the tumor tissue, PEG presents on the
      surface of liposomes, which is useful for passive accumulation in tumor tissue.
      Upon reaching the tumor tissues, the PEG chain could be removed by a safe
      cleaving reagent l-cysteine (l-Cys), and thus, the steric hindrance of PEG could
      be overcome conveniently. To further improve the uptake of liposomes, a
      "functional molecule" cell-penetrating peptide TAT was attached to the distal end
      of a shorter PEG spacer anchored to the surface of the liposomes, which could be
      shielded by cleavable PEG during circulation; upon arriving at tumor tissue, PEG
      was removed and thus the "functional molecule" TAT was exposed, and then TAT
      could mediate the uptake of the liposomes with high efficiency. In this study,
      thiolytic cleavable PEG was synthesized via a disulfide bridge, DOPE-PEG(1600)
      TAT was synthesized by sulfhydryl-maleimide reaction, and then Rh-PE labeled
      liposomes composed of 2% DOPE-PEG(1600)-TAT and various amounts of cleavable
      PEG(5000) (2%, 4%, and 8%) were prepared, with particle size around 100 nm and
      slightly negative charge. These liposomes showed good stability in the presence
      of 10% serum. Their uptake by tumor cells HepG2 in vitro was assessed
      qualitatively and quantitatively. Liposomes modified with 2% DOPE-PEG(1600)-TAT
      and 8% DOPE-S-S-mPEG(5000) were regarded as the optimal formulation. In this
      preparation, nearly no uptake could be observed before addition of l-Cys, which
      meant undesired uptake during circulation could be avoided, while the uptake upon
      addition of l-Cys was 4 times as high as that in the absence of l-Cys. For the
      uptake in vivo, calcein loaded and Rh-PE labeled 8% cleavable PEG + 2% TAT
      modified liposomes were injected intratumorally into H22 tumor bearing mice.
      Confocal laser scanning microscopy (CLSM) showed that the uptake of 8% cleavable
      PEG + 2% TAT modified liposomes was much higher than that of 8% noncleavable PEG
      + 2% TAT modified liposomes in the presence of l-Cys. Thus, tumor targeted
      delivery could be achieved efficiently by the liposomal drug delivery system
      developed here in a controlled manner.

PMID- 20701289
TI  - A new intestinal cell culture model to discriminate the relative contribution of
      P-gp and BCRP on transport of substrates such as imatinib.
AB  - P-glycoprotein (P-gp/MDR1/ABCB1) and breast cancer resistance protein
      (BCRP/ABCG2) play an important role in transport of a wide variety of endogenous
      compounds, drugs and toxins. Transport of some drugs, for example the tyrosine
      kinase inhibitor imatinib, is influenced by both P-gp and BCRP. Establishing an
      intestinal Caco-2 cell culture model with specific knock-downs of P-gp and BCRP
      and double knock-down of both proteins, we aimed to elucidate the impact of each
      transporter on transport of imatinib. Stable single and double knock-downs of P
      gp and BCRP were obtained by RNA interference (RNAi). Transporter expression was
      measured on RNA and protein level using real-time RT-PCR and Western blot,
      respectively. Functional activity was quantified by transport of specific
      substrates across Caco-2 cells. MDR1 and BCRP mRNA expression was reduced to 75%
      and 90% compared to wild-type control in single MDR1- and BCRP-knock-down clones,
      respectively. In double knock-down clones, MDR1 expression decreased to 95% and
      BCRP expression to 80%. Functional activity of P-gp and BCRP was diminished as
      transport of the P-gp-specific substrate (3)H-digoxin and the BCRP-specific
      substrate (14)C-PhIP was augmented in the opposite direction, when the respective
      transporter was knocked down. Similar effects were observed by chemical
      inhibition of the respective transporter. Bidirectional transport studies with
      (14)C-imatinib revealed an abrogation of asymmetric transport when P-gp was
      knocked down, either in single or double knock-down clones compared to wild-type
      cells. This was not observed in single BCRP-knock-down clones. In conclusion,
      this newly established cell system with single and concomitant knock-down of P-gp
      and BCRP can be used to quantify the specific partial impact of the transporters
      on transport of substrates that are transported by both proteins. For imatinib
      transport, the contribution of P-gp seems to be more important compared to BCRP
      in this Caco-2 cell system.

PMID- 20701290
TI  - Investigating the impact of elevated levels of ozone on tropical wheat using
      integrated phenotypical, physiological, biochemical, and proteomics approaches.
AB  - Ozone (O3), a potent air pollutant and a significant greenhouse gas, has been
      recognized as a major component of global climate change. However, current
      increasing trends in its background level are projecting a more severe threat to
      natural and cultivated plants in the near future. The present study has been
      designed to evaluate the impact of elevated concentrations of O3 on phenotypical,
      physiological, and biochemical traits in two high-yielding cultivars of wheat,
      followed by analysis of the leaf proteome using one/two-dimensional gel
      electrophoresis (1-/2-DGE) coupled to immunoblotting and mass spectrometry
      analyses under near-natural conditions using open top chambers. Prominently, O3
      exposure caused specific foliar injury in both the wheat cultivars. Results also
      showed that O3 stress significantly decreased photosynthetic rate, stomatal
      conductance, and chlorophyll fluorescence kinetics (Fv/Fm) in test cultivars.
      Biochemical evaluations further revealed a higher loss in photosynthetic
      pigments, whereas a significantly induced antioxidant system under elevated O3
      concentrations pointed toward an ability of O3 to generate oxidative stress. 1
      DGE analysis showed drastic reductions in the abundantly present ribulose-1,5
      bisphosphate carboxylase/oxygenase (RuBisCO) large and small subunits. Western
      blot analysis confirmed induced accumulation of antioxidative enzymes like
      superoxide dismutase and ascorbate peroxidase protein(s) and common
      defense/stress-related thaumatin-like protein(s). 2-DGE analysis revealed a total
      of 38 differentially expressed protein spots, common in both the wheat cultivars.
      Among those, some major leaf photosynthetic proteins (including RuBisCO and
      RuBisCO activase) and important energy metabolism proteins (including ATP
      synthase, aldolase, and phosphoglycerate kinase) were drastically reduced,
      whereas some stress/defense-related proteins (such as harpin-binding protein and
      germin-like protein) were induced. In all, the present study reveals an intimate
      molecular network provoked by O3 affecting photosynthesis and triggering
      antioxidative defense and stress-related proteins culminating in accelerated
      foliar injury in wheat plants.

PMID- 20701291
TI  - Metabolic profiling and the metabolome-wide association study: significance level
      for biomarker identification.
AB  - High throughput metabolic profiling via the metabolome-wide association study
      (MWAS) is a powerful new approach to identify biomarkers of disease risk, but
      there are methodological challenges: high dimensionality, high level of
      collinearity, the existence of peak overlap within metabolic spectral data,
      multiple testing, and selection of a suitable significance threshold. We define
      the metabolome-wide significance level (MWSL) as the threshold required to
      control the family wise error rate through a permutation approach. We used 1H NMR
      spectroscopic profiles of 24 h urinary collections from the INTERMAP study. Our
      results show that the MWSL primarily depends on sample size and spectral
      resolution. The MWSL estimates can be used to guide selection of discriminatory
      biomarkers in MWA studies. In a simulation study, we compare statistical
      performance of the MWSL approach to two variants of orthogonal partial least
      squares (OPLS) method with respect to statistical power, false positive rate and
      correspondence of ranking of the most significant spectral variables. Our results
      show that the MWSL approach as estimated by the univariate t test is not
      outperformed by OPLS and offers a fast and simple method to detect disease
      related discriminatory features in human NMR urinary metabolic profiles.

PMID- 20701292
TI  - Position-specific secondary deuterium isotope effects on basicity of pyridine.
AB  - Secondary isotope effects (IEs) on basicities of various deuterated pyridine
      isotopologues and of 2,6-lutidine-2,6-(CD(3))(2) have been accurately measured in
      aqueous solution by an NMR titration method applicable to a mixture. Deuteration
      at any position of pyridine increases the basicity, but the IE per deuterium is
      largest for substitution at the 3-position and smallest for the 2-position, which
      is closest to the site of N-protonation, smaller even than that for 2-CD(3)
      substitution. Computations at the B3LYP/cc-pVTZ level overestimate the magnitude
      of the measured IEs but largely reproduce the variability with isotopic position.
      Because the calculated IEs are based on changes in vibrational frequencies on N
      protonation, the correspondence between calculated and experimental IEs implies
      that they arise from zero-point energies, rather than from inductive effects.

PMID- 20701293
TI  - Ionization behavior, stoichiometry of association, and accessibility of
      functional groups in the active layers of reverse osmosis and nanofiltration
      membranes.
AB  - We characterized the fully aromatic polyamide (PA) active layers of six
      commercial reverse osmosis (RO) and nanofiltration (NF) membranes and found that
      in contrast to their similar elemental composition, total concentration of
      functional groups, and degree of polymerization, the ionization behavior and
      spatial distribution of carboxylic (R-COOH) groups within the active layers can
      be significantly different. We also studied the steric effects experienced by
      barium ion (Ba2+) in the active layers by determining the fraction of carboxylate
      (R-COO-) groups accessible to Ba2+; such fraction, referred to as the
      accessibility ratio (AR), was found to vary within the range AR=0.40-0.81, and to
      be generally independent of external solution pH. Additionally, we studied an NF
      membrane with a sulfonated polyethersulfone (SPES) active layer, and found that
      the concentration of sulfonate (R-SO3-) groups in the active layer was 1.67 M,
      independent of external solution pH and approximately three times higher than the
      maximum concentration (approximately 0.45+/-0.25 M) of R-COO- groups in PA active
      layers. The R-SO3- groups were found to be highly accessible to Ba2+ (AR=0.95+/
      0.01).

PMID- 20701294
TI  - Degradation of methylmercury and its effects on mercury distribution and cycling
      in the Florida Everglades.
AB  - Methylmercury (MeHg) is recognized as one of the major water quality concerns in
      the Florida Everglades. Degradation of MeHg in the water is thought to be one of
      the most important processes to the cycling of MeHg, but there is a lack of
      quantitative estimations of its effect on the distribution and cycling of MeHg in
      this ecosystem. Stable isotope (Me201Hg) addition method was implemented to
      investigate the degradation of MeHg in the Everglades. By combining these results
      with the field monitoring data, effects of photodegradation on MeHg distribution
      and its contribution to MeHg cycling were estimated. The results indicate that
      degradation of MeHg in Everglades water is mediated by sunlight and that UV-A and
      UV-B radiations are the principal driver. The spatial pattern of MeHg
      photodegradation potential (PPD) generally illustrated an increasing trend from
      north to south in the Everglades, which was opposite to the distribution of MeHg
      in water column. Correlation analysis shows that MeHg concentration in the water
      had a significant negative relation to PPD, suggesting that photodegradation
      could play an important role in controlling the distribution of MeHg in
      Everglades water. Furthermore, about 31.4% of MeHg input into the water body was
      removed by photodegradation, indicating its importance in the biogeochemical
      cycling of MeHg in the Everglades. This percent reduction is much lower than that
      reported for other ecosystems, which could be caused by the higher concentration
      of DOC in the Everglades. The relatively slower degradation of MeHg could be one
      of the main reasons for the high ratio of MeHg to total mercury (THg) in this
      ecosystem.

PMID- 20701295
TI  - Ordered mesoporous crystalline gamma-Al2O3 with variable architecture and
      porosity from a single hard template.
AB  - In this paper, an efficient route is developed for controllable synthesis of
      ordered mesoporous alumina (OMA) materials with variable pore architectures and
      high mesoporosity, as well as crystalline framework. The route is based on the
      nanocasting pathway with bimodal mesoporous carbon as the hard template. In
      contrast to conventional reports, we first realize the possibility of creating
      two ordered mesopore architectures by using a single carbon hard template
      obtained from organic-organic self-assembly, which is also the first time such
      carbon materials are adopted to replicate ordered mesoporous materials. The
      mesopore architecture and surface property of the carbon template are rationally
      designed in order to obtain ordered alumina mesostructures. We found that the key
      factors rely on the unique bimodal mesopore architecture and surface
      functionalization of the carbon hard template. Namely, the bimodal mesopores (2.3
      and 5.9 nm) and the surface functionalities make it possible to selectively load
      alumina into the small mesopores dominantly and/or with a layer of alumina coated
      on the inner surface of the large primary mesopores with different thicknesses
      until full loading is achieved. Thus, OMA materials with variable pore
      architectures (similar and reverse mesostructures relative to the carbon
      template) and controllable mesoporosity in a wide range are achieved. Meanwhile,
      in situ ammonia hydrolysis for conversion of the metal precursor to its hydroxide
      is helpful for easy crystallization (as low as approximately 500 degrees C). Well
      crystallized alumina frameworks composed of gamma-Al(2)O(3) nanocrystals with
      sizes of 6-7 nm are obtained after burning out the carbon template at 600 degrees
      C, which is advantageous over soft-templated aluminas. The effects of synthesis
      factors are demonstrated and discussed relative to control experiments.
      Furthermore, our method is versatile enough to be used for general synthesis of
      other important but difficult-to-synthesize mesoporous metal oxides, such as
      magnesium oxide. We believe that the fundamentals in this research will provide
      new insights for rational synthesis of ordered mesoporous materials.

PMID- 20701296
TI  - Catalyst-free InGaN/GaN nanowire light emitting diodes grown on (001) silicon by
      molecular beam epitaxy.
AB  - Catalyst-free growth of (In)GaN nanowires on (001) silicon substrate by plasma
      assisted molecular beam epitaxy is demonstrated. The nanowires with diameter
      ranging from 10 to 50 nm have a density of 1-2 x 10(11) cm(-2). P- and n-type
      doping of the nanowires is achieved with Mg and Si dopant species, respectively.
      Structural characterization by high-resolution transmission electron microscopy
      (HRTEM) indicates that the nanowires are relatively defect-free. The peak
      emission wavelength of InGaN nanowires can be tuned from ultraviolet to red by
      varying the In composition in the alloy and "white" emission is obtained in
      nanowires where the In composition is varied continuously during growth. The
      internal quantum efficiency varies from 20-35%. Radiative and nonradiative
      lifetimes of 5.4 and 1.4 ns, respectively, are obtained from time-resolved
      photoluminescence measurements at room temperature for InGaN nanowires emitting
      at lambda = 490 nm. Green- and white-emitting planar LEDs have been fabricated
      and characterized. The electroluminescence from these devices exhibits negligible
      quantum confined Stark effect or band-tail filling effect.

PMID- 20701297
TI  - Alcoholysis of naturally occurring imides: misleading interpretation of
      antifungal activities.
AB  - The frequent presence of the sulfur-containing amide penangin (10) in leaf
      extracts of Glycosmis species turned out to be the result of decomposition of
      imides generated by extraction and storage in MeOH. Reinvestigation of Glycosmis
      mauritiana and G. cf. puberula with acetone revealed the presence of six imides.
      In addition to penimides A (1) and B (2) and ritigalin (6), three new
      derivatives, krabin (4), isokrabin (5), and methoxypenimide B (3), were isolated
      and identified by spectroscopic methods. All six imides were shown to be
      susceptible to different rates of methanolic cleavage, leading to their
      corresponding methyl esters and sulfur-containing amides. Whereas the
      decomposition products penangin (10), isopenangin (11), and sinharin (14) are
      known, the corresponding cleavage of methyl N-methylthiocarbamate (7) from
      ritigalin (6), monitored in situ by (1)H NMR spectroscopy, is described here for
      the first time. Its structure was further confirmed by GC-MS coupling. HPLC-UV
      comparison of many different samples of G. mauritiana, extracted with MeOH,
      revealed considerable chemical variations in sulfur-containing amides, strongly
      correlated with different antifungal potency. The lack of activity of many
      methanolic crude extracts can be explained by a preponderance of the inactive
      decomposition product penangin (10), whereas the corresponding naturally
      occurring imides penimides A (1) and B (2) and methoxypenimide B (3), extracted
      with acetone, showed high fungitoxic properties.

PMID- 20701298
TI  - Cloning and characterization of phenylalanine ammonia-lyase and cinnamate 4
      hydroxylase and pyranocoumarin biosynthesis in Angelica gigas.
AB  - Phenylalanine ammonia-lyase (PAL) and cinnamate 4-hydroxylase (C4H) are important
      enzymes in the phenylpropanoid pathway and also in the accumulation of decursin
      (1) and decursinol angelate (2), which are major secondary metabolites in
      Angelica gigas. Using PCR with degenerate primers targeted to conserved regions
      of available orthologous PAL and C4H sequences, cDNAs encoding PAL and C4H from
      A. gigas were isolated. Both genes were used to show the comparative
      developmental and inducible accumulation of mRNAs in different organs and in
      suspension cells of A. gigas. PAL and C4H were induced most strongly in response
      to 300 microM methyl jasmonate treatment at 6 and 12 h, respectively, and were
      highly expressed in the fine roots of A. gigas. Similarly, the production of 1
      and 2 was most prolific in the fine roots of the plant.

PMID- 20701299
TI  - Isolation of pandamarilactonine-H from the roots of Pandanus amaryllifolius and
      synthesis of epi-pandamarilactonine-H.
AB  - A new alkaloid (1a), named pandamarilactonine-H, which possesses a methyl-2
      (pyrrolidin-2-yl)acetate function, was isolated from the roots of Pandanus
      amaryllifolius. Eleven known alkaloids were also isolated. Unambiguous assignment
      of the structure of 1a, including the absolute configuration, was accomplished by
      spectroscopic analysis and total synthesis of its enantiomer.

PMID- 20701300
TI  - Trace analysis by low-field NMR: breaking the sensitivity limit.
AB  - Sensitivity poses a persistent challenge to NMR spectroscopy and magnetic
      resonance imaging (MRI). Nonhydrogenative para-hydrogen induced polarization (NH
      PHIP) has recently emerged as an efficient method to substantially increase the
      sensitivity of high-field NMR. Here, we report the feasibility of applying NH
      PHIP in the low-field NMR. A trace amount of pyridine of just a few nanoliters (
      approximately 12 nmol) in a 0.4 mL NMR sample (a concentration of 31 microM or
      10(16)/cm(3)) could be measured in a single scan by NH-PHIP. There is a striking
      difference in the signal-to-noise ratio (SNR) between thermal prepolarization and
      NH-PHIP: The SNR of the prepolarized (1)H NMR signal decreases linearly with
      decreasing (1)H concentration ([(1)H]) while the SNR in NH-PHIP experiments first
      increases with decreasing [(1)H], then remains constant over 2 orders of
      magnitude, and finally decreases linearly with decreasing [(1)H]. A hitherto
      unknown potential opens up for trace analysis by low-field NMR in the bio-,
      chemical, and material sciences.

PMID- 20701301
TI  - High-precision determination of the isotopic composition of dissolved iron in
      iron depleted seawater by double spike multicollector-ICPMS.
AB  - This work demonstrates the feasibility of the measurement of the isotopic
      composition of dissolved iron in seawater for an iron concentration range, 0.05-1
      nmol L(-1), allowing measurements in most oceanic waters, including Fe depleted
      waters of high nutrient low chlorophyll areas. It presents a detailed description
      of our previously published protocol, with significant improvements on detection
      limit and blank contribution. Iron is preconcentrated using a nitriloacetic acid
      superflow resin and purified using an AG 1-x4 anion exchange resin. The isotopic
      ratios are measured with a multicollector-inductively coupled plasma mass
      spectrometer (MC-ICPMS) Neptune, coupled with a desolvator (Aridus II or Apex-Q),
      using a (57)Fe-(58)Fe double spike mass bias correction. A Monte Carlo test shows
      that optimum precision is obtained for a double spike composed of approximately
      50% (57)Fe and 50% (58)Fe and a sample to double spike quantity ratio of
      approximately 1. Total procedural yield is 91 +/- 25% (2SD, n = 55) for sample
      sizes from 20 to 2 L. The procedural blank ranges from 1.4 to 1.1 ng, for sample
      sizes ranging from 20 to 2 L, respectively, which, converted into Fe
      concentrations, corresponds to blank contributions of 0.001 and 0.010 nmol L(-1),
      respectively. Measurement precision determined from replicate measurements of
      seawater samples and standard solutions is 0.08 per thousand (delta(56)Fe, 2SD).
      The precision is sufficient to clearly detect and quantify isotopic variations in
      the oceans, which so far have been observed to span 2.5 per thousand and thus
      opens new perspectives to elucidate the oceanic iron cycle.

PMID- 20701302
TI  - Preparation of surface imprinting polymer capped Mn-doped ZnS quantum dots and
      their application for chemiluminescence detection of 4-nitrophenol in tap water.
AB  - In this paper, Mn-doped ZnS quantum dots (QDs) capped by a molecularly imprinted
      polymer (MIP) were synthesized. The results showed a high selectivity of the MIP
      capped Mn-doped ZnS QDs toward the template molecule (4-nitrophenol) by QD
      fluorescence quenching. The application of MIP-capped Mn-doped ZnS QDs to the
      chemiluminescence (CL) system was also studied using a KIO(4)-H(2)O(2) system.
      This application combines the good selectivity of MIP with the high sensitivity
      of CL. The linear range of this CL system is from 0.1 to 40 microM, and the
      detection limit (DL) for 4-nitrophenol in the water can reach 76 nM. The method
      was also used in the real water samples, and the recoveries can fall in the range
      of 91-96%.

PMID- 20701305
TI  - Dissociative photoionization of sulfur chlorides and oxochlorides:
      thermochemistry and bond energies based on accurate appearance energies.
AB  - The dissociative photoionization of four compounds, SCl(2), S(2)Cl(2), SOCl(2),
      and SO(2)Cl(2), were measured with threshold and imaging photoelectron photoion
      coincidence spectrometry (TPEPICO and iPEPICO). In all systems, the molecular ion
      loses a chlorine atom in a fast dissociation. The 0 K appearance energies of the
      first chlorine-loss fragment ions were determined to be 12.252 +/- 0.012 eV,
      11.205 +/- 0.003 eV, 11.709 +/- 0.003 eV, and 12.505 +/- 0.003 eV, respectively.
      SCl(2) was measured on the laboratory-based TPEPICO instrument, in which the
      second Cl-loss dissociation could not be observed within the available photon
      energy. For S(2)Cl(2)(+) and SOCl(2)(+), the appearance energy of the fragment
      ion after two chlorine-loss dissociations were determined to be 13.32 +/- 0.02 eV
      and 14.88 +/- 0.02 eV, respectively. On the basis of the analysis of the
      breakdown curves, it was concluded that assuming three-dimensional translational
      degrees of freedom yields a more reliable statistical model of the product energy
      distributions. The literature heat of formation of the neutral precursor molecule
      thionyl chloride, SOCl(2) does not agree with our results based on the SO(+)
      cation and is revised by more than 10 kJ mol(-1) to -198.2 +/- 2.4 kJ mol(-1). A
      particularly broad Franck-Condon gap with vanishingly small threshold electron
      signal in the photon energy range for the second Cl-loss reaction in
      SO(2)Cl(2)(+) is discussed with regard to the mechanism of threshold ionization.

PMID- 20701306
TI  - Ring deformation and pi-electron redistribution of methylbenzenes induced by
      metal coordination.
AB  - Scandium (Sc) complexes of p-xylene, mesitylene, and hexamethylbenzene were
      produced in a laser-vaporization molecular beam source and studied with pulsed
      field-ionization zero-electron-kinetic-energy spectroscopy, and density
      functional theory. In addition, infrared-ultraviolet resonant two-photon
      ionization spectra were recorded for Sc(hexamethylbenzene) in the C-H stretching
      region. Adiabatic ionization energies and several vibrational frequencies of
      these complexes were obtained from the spectroscopic measurements, and electronic
      transitions were determined by combining the spectra with the theoretical data.
      The ionization energies of the three complexes decrease with increasing number of
      the methyl groups, whereas the metal-ligand stretching frequencies of the p
      xylene and mesitylene complexes are essentially the same and slightly smaller
      than that of the hexamethylbenzene species. Unlike benzene, the arene ring of the
      methylbenzene molecules is bent and the pi-electrons are localized in a 1,4-diene
      fashion upon Sc coordination. The distortion of the aromatic ring is due to
      differential metal binding with the ring carbon atoms in the low-spin ground
      electronic state.

PMID- 20701307
TI  - Splaying of aliphatic tails plays a central role in barrier crossing during
      liposome fusion.
AB  - The fusion between two lipid bilayers involves crossing a complicated energy
      landscape. The limiting barrier in the process appears to be between two closely
      opposed bilayers and the intermediate state where the outer leaflets are fused.
      We have performed molecular dynamics simulations to characterize the free energy
      barrier for the fusion of two liposomes and to examine the molecular details of
      barrier crossing. To capture the slow dynamics of fusion, a model using coarse
      grained representations of lipids was used. The fusion between pairs of liposomes
      was simulated for four systems: DPPC, DOPC, a 3:1 mixture of DPPC/DPPE, and an
      asymmetric lipid tail system in which one tail of DPPC was reduced to half the
      length (ASTail). The weighted histogram method was used to compute the free
      energy as a function of separation distance. The relative barrier heights for
      these systems was found to be ASTail >> DPPC > DPPC/DPPE > DOPC, in agreement
      with experimental observations. Further, the free energy curves for all four can
      be overlaid on a single curve by plotting the free energy versus the surface
      separation (differing only in the point of fusion). These simulations also
      confirm that the two main contributions to the free energy barrier are the
      removal of water between the vesicles and the deformation of the vesicle. The
      most prominent molecular detail of barrier crossing in all cases examined was the
      splaying of lipid tails, where initially a single splayed lipid formed a bridge
      between the two outer leaflets that promotes additional lipid mixing between the
      vesicles and eventually leads to fusion. The tail splay appears to be closely
      connected to the energetics of the process. For example, the high barrier for the
      ASTail is the result of a smaller distance between terminal methyl groups in the
      splayed molecule. The shortening of this distance requires the liposomes to be
      closer together, which significantly increases the cost of water removal and
      bilayer deformation. Before tail splay can initiate fusion, contact must occur
      between a tail end and the external water. In isolated vesicles, the contact
      fraction is correlated to the fusogenicity difference between DPPC and DOPC.
      Moreover, for planar bilayers, the contact fraction is much lower for DPPC, which
      is consistent with its lack of fusion in giant vesicles. The simulation results
      show the key roles of lipid tail dynamics in governing the fusion energy
      landscape.

PMID- 20701308
TI  - Self-assembly of alkali-uranyl-peroxide clusters.
AB  - The hexavalent uranium specie, uranyl triperoxide, UO(2)(O(2))(3)(4-), has been
      shown recently to behave like high oxidation-state d(0) transition-metals, self
      assembling into polyoxometalate-like clusters that contain up to 60 uranyl
      cations bridged by peroxide ligands. There has been much less focus on synthesis
      and structural characterization of salts of the monomeric UO(2)(O(2))(3)(4-)
      building block of these clusters. However, these could serve as water-soluble
      uranyl precursors for both clusters and materials, and also be used as simple
      models to study aqueous behavior by experiment and modeling. The countercation is
      of utmost importance to the assembly of these clusters, and Li(+) has proven
      useful for the crystallization of many of the known cluster geometries to date.
      We present in this paper synthesis and structural characterization of two
      monomeric lithium uranyl-peroxide salts, Li(4)[UO(2)(O(2))(3)] x 10 H(2)O (1) and
      [UO(2)(O(2))(3)](12)[(UO(2)(OH)(4))Li(16)(H(2)O)(28)](3) x Li(6)[H(2)O](26) (2).
      They were obtained from aqueous-alcohol solutions rather than the analogous
      aqueous solutions from which lithium uranyl-peroxide clusters are crystallized.
      Rapid introduction of the alcohol gives the structure of (1) whereas slow
      diffusion of alcohol results in crystallization of (2). (2) is an unusual
      structure featuring uranyl-centered alkali clusters that are linked into ring and
      spherical arrangements via [UO(2)(O(2))(3)] anions. Furthermore, partial
      substitution of Rb or Cs into the synthesis results in formation of (2) with
      substitution of these larger alkalis into the uranyl-centered clusters. We
      surmise that the slow crystallization allows for direct bonding of alkali metals
      to the uranyl-peroxide oxygen ligands that is observed in (2), and its Rb and Cs
      substituted derivatives. In contrast, the only interaction between
      UO(2)(O(2))(3)(4-) and Li(+) observed in (1) is through hydrogen bonding of the
      lithium-bound water. These structures potentially provide some insight to
      understanding how alkali counterions interact with the UO(2)(O(2))(3)(4-) anions
      during the self-assembly, crystallization and even redissolution of uranyl
      peroxide polyanionic clusters.

PMID- 20701309
TI  - The anionic (9-methyladenine)-(1-methylthymine) base pair solvated by formic
      acid. A computational and photoelectron spectroscopy study.
AB  - The photoelectron spectrum for (1-methylthymine)-(9-methyladenine)...(formic
      acid) (1MT-9MA...FA) anions with the maximum at ca. 1.87 eV was recorded with
      2.54 eV photons and interpreted through the quantum-chemical modeling carried out
      at the B3LYP/6-31+G(d,p) level. The relative free energies of the anions and
      their calculated vertical detachment energies suggest that only seven anionic
      structures contribute to the observed PES signal. We demonstrate that electron
      binding to the (1MT-9MA...FA) complex can trigger intermolecular proton transfer
      from formic acid, leading to the strong stabilization of the resulting radical
      anion. The SOMO distribution indicates that an excess electron may localize not
      only on the pyrimidine but also on the purine moiety. The biological context of
      DNA-environment interactions concerning the formation of single-strand breaks
      induced by excess electrons has been briefly discussed.

PMID- 20701310
TI  - Picosecond protein dynamics: the origin of the time-dependent spectral shift in
      the fluorescence of the single Trp in the protein GB1.
AB  - How a biological system responds to a charge shift is a challenging question
      directly relevant to biological function. Time-resolved fluorescence of a
      tryptophan residue reflects protein and solvent response to the difference in pi
      electron density between the excited and the ground state. In this study we use
      molecular dynamics to calculate the time-dependent spectral shift (TDSS) in the
      fluorescence of Trp-43 in GB1 protein. A new computational method for separating
      solvent, protein, and fluorophore contributions to TDSS is applied to 100
      nonequilibrium trajectories for GB1 in TIP3P water. The results support several
      nontrivial conclusions. Both longitudinal and transverse relaxation modes of bulk
      solvent contribute to the TDSS in proteins. All relaxation components slower than
      the transverse relaxation of bulk solvent have significant contributions from
      both protein and solvent, with a negative correlation between them. Five
      exponential terms in the TDSS of GB1 are well separated by their relaxation
      times. A 0.036 ps term is due to both solvent (60%) and protein (40%). Two
      exponential terms represent longitudinal (tau(L) approximately = 0.4 ps) and
      transverse (tau(D) approximately = 5.6 ps) relaxation modes of TIP3P water. A 131
      ps term is attributable to a small change in the tertiary structure, with the
      alpha-helix moving 0.2 A away from the beta-strand containing Trp-43. A 2580 ps
      term is due to the change in the conformation of the Glu-42 side chain that
      brings its carboxyl group close to the positively charged end of the excited
      fluorophore. Interestingly, water cancels 60% of the TDSS resulting from this
      conformational change.

PMID- 20701311
TI  - Stereoselective hydrolysis of organophosphate nerve agents by the bacterial
      phosphotriesterase.
AB  - Organophosphorus compounds include many synthetic, neurotoxic substances that are
      commonly used as insecticides. The toxicity of these compounds is due to their
      ability to inhibit the enzyme acetylcholine esterase. Some of the most toxic
      organophosphates have been adapted for use as chemical warfare agents; the most
      well-known are GA, GB, GD, GF, VX, and VR. All of these compounds contain a
      chiral phosphorus center, with the S(P) enantiomers being significantly more
      toxic than the R(P) enantiomers. Phosphotriesterase (PTE) is an enzyme capable of
      detoxifying these agents, but the stereochemical preference of the wild-type
      enzyme is for the R(P) enantiomers. A series of enantiomerically pure chiral
      nerve agent analogues containing the relevant phosphoryl centers found in GB, GD,
      GF, VX, and VR has been developed. Wild-type and mutant forms of PTE have been
      tested for their ability to hydrolyze this series of compounds. Mutant forms of
      PTE with significantly enhanced, as well as relaxed or reversed,
      stereoselectivity have been identified. A number of variants exhibited
      dramatically improved kinetic constants for the catalytic hydrolysis of the more
      toxic S(P) enantiomers. Improvements of up to 3 orders of magnitude relative to
      the value of the wild-type enzyme were observed. Some of these mutants were
      tested against racemic mixtures of GB and GD. The kinetic constants obtained with
      the chiral nerve agent analogues accurately predict the improved activity and
      stereoselectivity against the authentic nerve agents used in this study.

PMID- 20701312
TI  - 1H NMR spectroscopy-based interventional metabolic phenotyping: a cohort study of
      rheumatoid arthritis patients.
AB  - 1H NMR spectroscopy-based metabolic phenotyping was used to identify biomarkers
      in the plasma of patients with rheumatoid arthritis (RA). Forty-seven patients
      with RA (23 with active disease at baseline and 24 in remission) and 51 healthy
      subjects were evaluated during a one-year follow-up with assessments of disease
      activity (DAS-28) and 1H NMR spectroscopy of plasma samples. Discriminant
      analysis provided evidence that the metabolic profiles predicted disease
      severity. Cholesterol, lactate, acetylated glycoprotein, and lipid signatures
      were found to be candidate biomarkers for disease severity. The results also
      supported the link between RA and coronary artery disease. Repeated assessment
      using mixed linear models showed that the predictors obtained from metabolic
      profiles of plasma at baseline from patients with active RA were significantly
      different from those of patients in remission (P=0.0007). However, after 31 days
      of optimized therapy, the two patient groups were not significantly different
      (P=0.91). The metabolic profiles of both groups of RA patients were different
      from the healthy subjects. 1H NMR-based metabolic phenotyping of plasma samples
      in patients with RA is well suited for discovery of biomarkers and may be a
      potential approach for disease monitoring and personalized medication for RA
      therapy.

PMID- 20701313
TI  - Excitation-dependent fluorescence of triphenylamine-substituted tridentate
      pyridyl ruthenium complexes.
AB  - Two polypyridyl ruthenium complexes, bis[4-(N,N'-diphenylamino)phenyl-2,2':6',2''
      terpyridine]ruthenium(II) (1) and bis[4'-(4-{2-[4-(N,N'
      diphenylamino)phenyl]ethylene}phenyl)-2, 2':6',2''-terpyridine]ruthenium(II) (2),
      have been synthesized. They possess an extended conjugation and strongly coupled
      electronic states. The features of these compounds were carefully studied from
      several respects. Steady-state spectroscopy showed that the two compounds had
      strong excitation dependent emission behaviors caused by mixing features of
      different electronic states. Femtosecond fluorescence upconversion spectroscopy
      was also used to investigate the fluorescence dynamics of the compounds. An
      ultrafast relaxation time of approximately 100 fs of the (1)MLCT (metal-to-ligand
      charge-transfer) states, which may originate from an ultrafast intersystem
      crossing to form (3)MLCT states, was found in both samples. However, thermal
      populated states and vibration associated excited state interactions were
      suggested for 1 with excitation at wavelengths below 400 nm, whereas vibrational
      energy redistribution with a time scale of few picoseconds was observed in the
      extended conjugated system of 2. These compounds will have potential application
      in both artificial photosynthesis systems and photovoltaic devices.

PMID- 20701314
TI  - Polycyclic aromatic hydrocarbon detection by electrochemiluminescence generating
      Ag/TiO(2) nanotubes.
AB  - Highly ordered TiO(2) nanotube arrays are with unique photoelectrical properties
      due to their highly ordered nanostructure and the resulted short charge
      transportation path. We report, for the first time, on the application of Ag
      nanoparticle-modified TiO(2) nanotubes (Ag/TiO(2) NTs) in the
      electrochemiluminescence detection of polycyclic aromatic hydrocarbons (PAHs)
      using the Ag/TiO(2) NT film as working electrode and S(2)O(8)(2-) as coreactant,
      with benzo(a)pyrene (BaP) as the model compound. The hydrophobic BaP absorbs onto
      the TiO(2) NTs surface, and oxidized with consumption of the excited TiO(2)
      (TiO(2)(*+)) resulting in a decrease in ECL. Under the optimal conditions, a
      detection limit of 1.0 x 10(-12) M is achieved with a linear range of 3.0 x 10(
      12) approximately 1.0 x 10(-9) M. Compounds which can not be oxidized by the
      excited TiO(2) (TiO(2)(*+)), such as benzene, naphthalene (NAP), anthracene
      (ANT), and tris-2,3-dibrominepropyl isocyanurate (TBC) show little interference
      on the detection, whereas PAHs with more than four rings can be detected by the
      proposed method.

PMID- 20701316
TI  - Active iron-rich belite sulfoaluminate cements: clinkering and hydration.
AB  - Ordinary Portland cement (OPC) is an environmentally contentious material, as for
      every ton of OPC produced, on average, 0.97 tons of CO2 are released. Conversely,
      belite sulfoaluminate (BSA) cements are promising eco-friendly building
      materials, as their production may deplete CO2 emissions up to 35% (compared to
      OPC). However, the hydration rate of belite is slow. Here, we report the
      clinkering of iron-rich BSA materials, their activation with B2O3, and
      establishing a methodology to measure their improved reactivities. Nonactivated
      BSA clinker contained only beta belite phase, 52 wt %. Meanwhile, BSA clinkers
      activated with 1 and 2 wt % of B2O3 contained 28 wt % of beta and 25 wt % of
      alpha'H; and 54 wt % of alpha'H phase, respectively. Therefore, activation of BSA
      has been proved as alpha'H-belite is stabilized. The hydration of the cements has
      been studied by laboratory and synchrotron X-ray powder diffraction (using
      Rietveld method and chemical constraints), calorimetry, and environmental
      scanning electron microscopy. Cement pastes have different hydration rates. For
      nonactivated BSA cement, 20 and 48% of the belite reacted after one and three
      months, respectively. Conversely, 37-49% after one month and 52-62% after three
      months of overall belite reactivities have been measured for BSA cements
      activated with B2O3.

PMID- 20701315
TI  - A solanesol-derived scaffold for multimerization of bioactive peptides.
AB  - A flexible molecular scaffold bearing varying numbers of terminal alkyne groups
      was synthesized in five steps from solanesol. R(CO)-MSH(4)-NH(2) ligands, which
      have a relatively low affinity for binding at the human melanocortin 4 receptor
      (hMC4R), were prepared by solid phase synthesis and were N-terminally acylated
      with 6-azidohexanoic acid. Multiple copies of the azide N(3)(CH(2))(5)(CO)-MSH(4)
      NH(2) were attached to the alkyne-bearing, solanesol-derived molecular scaffold
      via the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. Control
      studies showed that the binding affinity of the triazole-containing ligand,
      CH(3)(CH(2))(3)(C(2)N(3))(CH(2))(5)(CO)-MSH(4)-NH(2), was not significantly
      diminished relative to the corresponding parental ligand, CH(3)(CO)-MSH(4)-NH(2).
      In a competitive binding assay with a Eu-labeled probe based on the superpotent
      ligand NDP-alpha-MSH, the monovalent and multivalent constructs appear to bind to
      hMC4R as monovalent species. In a similar assay with a Eu-labeled probe based on
      MSH(4), modest increases in binding potency with increased MSH(4) content per
      scaffold were observed.

PMID- 20701317
TI  - Asymmetric total synthesis of trilobacin via organoselenium-mediated oxonium ion
      formation/SiO2-promoted fragmentation.
AB  - An asymmetric total synthesis of trilobacin (1), an annonaceous acetogenin with
      potent anticancer activities, was accomplished wherein the construction of its
      erythro-bis(2,2')-tetrahydrofuran core 2 featured a novel organoselenium-mediated
      oxonium ion formation/SiO(2)-promoted fragmentation of alpha,alpha'-cis-oxocene
      3.

PMID- 20701318
TI  - Cyclic alkenyl boronic half acid synthesis and applications.
AB  - The synthesis of cyclic alkenyl boronic half acids from vinyl and propenyl
      boronic esters and homoallylic alcohols by ring-closing metathesis is reported.
      The method is compatible with both conventional and microwave heating and
      comparable yields are obtained under both conditions. The cyclic alkenyl boronic
      acids participate in Suzuki-Miyaura coupling reactions in good yields.

PMID- 20701319
TI  - Direct asymmetric hydrogenation of 2-oxo-4-arylbut-3-enoic acids.
AB  - A challenging direct asymmetric hydrogenation of (E)-2-oxo-4-arylbut-3-enoic
      acids to give 2-hydroxy-4-arylbutanoic acids (85.4-91.8% ee) was achieved with a
      Ru catalyst based on SunPhos as the chiral ligand. Further investigation of the
      reaction revealed that partial isomerization of 2-hydroxy-4-arylbutenoic acids
      was involved in the hydrogenation process. Employing the reaction conditions to
      the hydrogenation of 2-oxo-4-phenylbutanoic acid resulted in better
      enantioselectivity (91.8% ee) and efficiency (TON = 2000, TOF = 200 h(-1)), which
      offers a useful method for the synthesis of a common intermediate for ACE
      inhibitors.

PMID- 20701320
TI  - Density functional theory study on the mechanism of the reductive cleavage of CO2
      by a bis-beta-diketoiminatediiron dinitrogen complex.
AB  - Density functional theory has been used to analyze the detailed reaction
      mechanism for the reductive cleavage of CO(2) by a dinitrogen bridged bis-beta
      diketoiminatediiron complex, L(tBu)Fe-N(2)-FeL(tBu) (I), recently reported by
      Holland and co-workers. A number of pathways have been investigated and the most
      likely mechanism correlates well with experimental evidence. A rationale has been
      provided for the binding of CO(2), the release of CO, and the ready formation of
      CO(3)(2-). Our results show that the insertion of CO(2) into the diiron complex
      is the rate determining step of the reductive cleavage reaction. An
      intramolecular reduction step from the reduced dinitrogen bridge is proposed
      which serves to increase the activation of CO(2). This is followed by an
      intersystem crossing from the septet to the nonet state which acts as a driving
      force for the subsequent release of CO. The overall reductive cleavage reaction
      is exergonic by 120 kJ/mol, and further reaction of the released CO with the
      starting diiron complex is also predicted to be strongly exergonic.

PMID- 20701321
TI  - Magnetically induced currents in [n]cycloparaphenylenes, n = 6-11.
AB  - We report calculations of the gauge-independent magnetically induced current
      densities in [n]cycloparaphenylenes ([n]CP), n = 6-11. In addition to the neutral
      [n]CPs, the dianion of [6]CP and the current densities of the corresponding metal
      complexes Li(2)[6]CP and Mg[6]CP are also investigated. By the ring current
      criterion, the [6]CP with 4n pi electrons has a slight antiaromatic character,
      while [7]CP has (4n + 2) pi electrons and is weakly aromatic with a ring current
      susceptibility strength that is about 25% of the ring current of benzene. The
      larger neutral [n]CPs, n = 8-11, do not sustain any net ring current around the
      nanohoop and are essentially nonaromatic. The weak paramagnetic ring current
      susceptibility of [6]CP flows along a 4n pi pathway on either edge of the
      phenylene rings. For the dianions, the ring current susceptibility strengths are
      24-35 nA/T diatropic and thus the addition of two electrons induces an electron
      delocalization and an aromatic character of the nanohoops. The dilithium complex
      of [6]CP with (4n + 2) pi electrons is aromatic with a net ring current strength
      of 28 nA/T or 2.4 times the ring current strength of benzene, involving all 62 pi
      electrons in the current pathway. The (1)H NMR chemical shieldings and the
      nucleus-independent chemical shifts correlate with the strengths of the
      magnetically induced currents. The aromatic [n]cycloparaphenylenes have a quinoid
      structure, whereas the weakly aromatic or nonaromatic ones are benzoidic.

PMID- 20701322
TI  - Computational studies of the isomerization and hydration reactions of
      acetaldehyde oxide and methyl vinyl carbonyl oxide.
AB  - Alkene ozonolysis is a major source of hydroxyl radical (*OH), the most important
      oxidant in the troposphere. Previous experimental and computational work suggests
      that for many alkenes the measured *OH yields should be attributed to the
      combined impact of both chemically activated and thermalized syn-alkyl Criegee
      intermediates (CIs), even though the thermalized CI should be susceptible to
      trapping by molecules such as water. We have used RRKM/master equation and
      variational transition state theory calculations to quantify the competition
      between unimolecular isomerization and bimolecular hydration reactions for the
      syn and anti acetaldehyde oxide formed in trans-2-butene ozonolysis and for the
      CIs formed in isoprene ozonolysis possessing syn-methyl groups. Statistical rate
      theory calculations were based on quantum chemical data provided by the B3LYP,
      QCISD, and multicoefficient G3 methods, and thermal rate constants were corrected
      for tunneling effects using the Eckart method. At tropospheric temperatures and
      pressures, all thermalized CIs with syn-methyl groups are predicted to undergo
      1,4-hydrogen shifts from 2 to 8 orders of magnitude faster than they react with
      water monomer at its saturation number density. For thermalized anti acetaldehyde
      oxide, the rates of dioxirane formation and hydration should be comparable.

PMID- 20701323
TI  - [Cu3(Hmesox)3]3-: a precursor for the rational design of chiral molecule-based
      magnets (H4mesox = 2-dihydroxymalonic acid).
AB  - Two new compounds K(3)[Cu(3)(Hmesox)(3)(H(2)O)] x 4 H(2)O (1) and
      {(PPh(4))(2)[CoCu(3)(Hmesox)(3)Cl]} (2) [H(4)mesox = mesoxalic acid (2
      dihydroxymalonic acid) and PPh(4)(+) = tetraphenylphosphonium cation] have been
      prepared and magneto-structurally characterized. Compound 1 contains the
      [Cu(3)(Hmesox)(3)](3-) entity which can be considered as a new precursor for
      molecular magnetism. In 1 the triangular arrangement of three copper(II) ions
      bridged by alkoxo groups are further connected to a symmetry-related
      tricopper(II) unit through a double oxo(carboxylate) bridge. The resulting
      hexacopper(II) entities are joined further through anti-syn carboxylate groups
      into an anionic three-dimensional network of formula
      [Cu(3)(Hmesox)(3)(H(2)O)](n)(3n-) whose charge is neutralized by univalent
      potassium cations. The strong decrease of the chi(M)T product [per three
      copper(II) ions] in the high temperature range with the occurrence of a plateau
      for a spin doublet at T < 65 K is as expected for the coexistence of two
      antiferromagnetic interactions within the quasi isosceles tricopper(II) core of 1
      [J = -194(1) cm(-1) and j = -3(4) cm(-1), the Hamiltonian being defined as H = 
      J(S(1) x S(2) + S(2) x S(3)) - j(S(1) x S(2))]. Compound 2 exhibits a chiral
      three-dimensional structure which is made up of an anionic [Co(II)Cu(II)(3)(mu(3)
      Cl)(Hmesox)(3)](n)(2n-) framework with a (10,3)-a topology whose cavities are
      filled by PPh(4)(+) cations. The [Cu(II)(3)(mu(3)-Cl)(Hmesox)(3)](3-)
      tricopper(II) unit in 2 acts as a tris-bidentate ligand through the Hmesox groups
      toward three cobalt(II) ions, these latter ones being tris-chelated. Alternating
      current (ac) and direct current (dc) magnetic susceptibility measurements of 2
      show a ferrimagnetic behavior with a magnetic ordering at T(c) = 18.5 K and a
      coercive field H(c) = 5000 G. As shown by the magneto-structural study of 2, the
      use as a ligand of 1 versus metal ions other than cobalt(II) or preformed
      complexes whose coordination sphere is partially blocked represents a new and
      rational preparative route toward multifunctional heterometallic compounds.

PMID- 20701324
TI  - Use of a reduced Schiff-Base ligand to prepare novel chloro-bridged chains of
      rare Cu(II) trinuclear complexes with mixed azido/oxo and chloro/oxo bridges.
AB  - Two mixed bridged one-dimensional (1D) polynuclear complexes, [Cu(3)L(2)(mu(1,1)
      N(3))(2)(mu-Cl)Cl](n) (1) and {[Cu(3)L(2)(mu-Cl)(3)Cl].0.46CH(3)OH}(n) (2), have
      been synthesized using the tridentate reduced Schiff-base ligand HL (2-[(2
      dimethylamino-ethylamino)-methyl]-phenol). The complexes have been characterized
      by X-ray structural analyses and variable-temperature magnetic susceptibility
      measurements. In both complexes the basic trinuclear angular units are joined
      together by weak chloro bridges to form a 1D chain. The trinuclear structure of 1
      is composed of two terminal square planar [Cu(L)(mu(1,1)-N(3))] units connected
      by a central Cu(II) atom through bridging nitrogen atoms of end-on azido ligands
      and the phenoxo oxygen atom of the tridentate ligand. These four coordinating
      atoms along with a chloride ion form a distorted trigonal bipyramidal geometry
      around the central Cu(II). The structure of 2 is similar; the only difference
      being a Cl bridge replacing the mu(1,1)-N(3) bridge in the trinuclear unit. The
      magnetic properties of both trinuclear complexes can be very well reproduced with
      a simple linear symmetrical trimer model (H = -JS(i)S(i+1)) with only one
      intracluster exchange coupling (J) including a weak intertrimer interaction (j)
      reproduced with the molecular field approximation. This model provides very
      satisfactory fits for both complexes in the whole temperature range with the
      following parameters: g = 2.136(3), J = -93.9(3) cm(-1) and zj = -0.90(3) cm(-1)
      (z = 2) for 1 and g = 2.073(7), J = -44.9(4) cm(-1) and zJ' = -1.26(6) cm(-1) (z
      = 2) for 2.

PMID- 20701325
TI  - Multiconformation continuum electrostatics analysis of the effects of a buried
      Asp introduced near heme a in Rhodobacter sphaeroides cytochrome c oxidase.
AB  - Cytochrome c oxidase (CcO) reduces O(2) to water via a series of proton-coupled
      electron transfers, generating a transmembrane electrochemical gradient. Coupling
      electron and proton transfer requires changing the pK(a) values of buried
      residues at each stage in the reaction cycle. Heme a is a key cofactor in the CcO
      electron transfer chain. Mutation of Ser44 to Asp has been reported [Mills, D.
      A., et al. (2008) Biochemistry 47, 11499-11509], changing the hydrogen bond
      acceptor from His102, the heme a axial ligand in Rhodobactor sphaeroides CcO.
      This adds an acidic residue to the CcO interior. The electrochemical behavior of
      heme a in wild-type and S44D CcO is compared using the continuum electrostatics
      program MCCE. The introduced, deeply buried Asp remains ionized at physiological
      pH only when the nearby heme is oxidized. Heme a reduction is now calculated to
      be strongly coupled to Asp proton binding, while with Ser44, it is weakly coupled
      to small protonation shifts at multiple sites, increasing the pH dependence in
      the mutant. At pH 7, the partially ionized Asp 44 is calculated to lower the heme
      redox potential by 50 mV as expected given the thermodynamics of coupled electron
      and proton transfers. This highlights an curious finding in the experimental
      results where a low Asp pK(a) is found together with a stabilized reduced heme.
      The stabilization of a heme oxidation in a model complex by a hydrogen bond to
      the axial His ligand calculated with continuum electrostatics and with density
      functional theory were in good agreement.

PMID- 20701326
TI  - High-permeability criterion for BCS classification: segmental/pH dependent
      permeability considerations.
AB  - The FDA classifies a drug substance as high-permeability when the fraction of
      dose absorbed (F(abs)) in humans is 90% or higher. This direct correlation
      between human permeability and F(abs) has been recently controversial, since the
      beta-blocker sotalol showed high F(abs) (90%) and low Caco-2 permeability. The
      purpose of this study was to investigate the scientific basis for this disparity
      between permeability and F(abs). The effective permeabilities (P(eff)) of sotalol
      and metoprolol, a FDA standard for the low/high P(eff) class boundary, were
      investigated in the rat perfusion model, in three different intestinal segments
      with pHs corresponding to the physiological pH in each region: (1) proximal
      jejunum, pH 6.5; (2) mid small intestine, pH 7.0; and (3) distal ileum, pH 7.5.
      Both metoprolol and sotalol showed pH-dependent permeability, with higher P(eff)
      at higher pH. At any given pH, sotalol showed lower permeability than metoprolol;
      however, the permeability of sotalol determined at pH 7.5 exceeded/matched
      metoprolol's at pH 6.5 and 7.0, respectively. Physicochemical analysis based on
      ionization, pK(a) and partitioning of these drugs predicted the same trend and
      clarified the mechanism behind these observed results. Experimental octanol
      buffer partitioning experiments confirmed the theoretical curves. An oral dose of
      metoprolol has been reported to be completely absorbed in the upper small
      intestine; it follows, hence, that metoprolol's P(eff) value at pH 7.5 is not
      likely physiologically relevant for an immediate release dosage form, and the
      permeability at pH 6.5 represents the actual relevant value for the low/high
      permeability class boundary. Although sotalol's permeability is low at pH 6.5 and
      7.0, at pH 7.5 it exceeds/matches the threshold of metoprolol at pH 6.5 and 7.0,
      most likely responsible for its high F(abs). In conclusion, we have shown that,
      in fact, there is no discrepancy between P(eff) and F(abs) in sotalol's
      absorption; the data emphasize that, if a compound has high fraction of dose
      absorbed, it will have high-permeability, not necessarily in the jejunum, but at
      some point along the relevant intestinal regions.

PMID- 20701327
TI  - Development and application of a biorelevant dissolution method using USP
      apparatus 4 in early phase formulation development.
AB  - Dissolution testing is frequently used to determine the rate and extent at which
      a drug is released from a dosage form, and it plays many important roles
      throughout drug product development. However, the traditional dissolution
      approach often emphasizes its application in quality control testing and usually
      strives to obtain 100% drug release. As a result, dissolution methods are not
      necessarily biorelevant and meaningful application of traditional dissolution
      methods in the early phases of drug product development can be very limited. This
      article will describe the development of a biorelevant in vitro dissolution
      method using USP apparatus 4, biorelevant media, and real-time online UV
      analysis. Several case studies in the areas of formulation selection, lot-to-lot
      variability, and food effect will be presented to demonstrate the application of
      this method in early phase formulation development. This biorelevant dissolution
      method using USP apparatus 4 provides a valuable tool to predict certain aspects
      of the in vivo drug release. It can be used to facilitate the formulation
      development/selection for pharmacokinetic (PK) and clinical studies. It may also
      potentially be used to minimize the number of PK studies, and to aid in the
      design of more efficient PK and clinical studies.

PMID- 20701328
TI  - Neta-substituted arginyl peptide inhibitors of protein arginine N
      methyltransferases.
AB  - Protein arginine N-methyltransferases (PRMTs) catalyze the post-translational
      methylation of arginine residues within substrate proteins. Their roles in the
      epigenetic regulation of gene expression make them viable targets for drug
      discovery. Peptides containing a single arginine residue substituted at the
      guanidino nitrogen (N(eta)) with an ethyl group bearing zero to three fluorine
      atoms (R1-1, -2, -3, and -4) have been synthesized and tested for methylation and
      inhibition activity with PRMT1, PRMT6, and CARM1. Only the nonfluorinated R1-1
      peptide is methylated by PRMT1, demonstrating that the N(eta)-substituted
      arginine is accommodated by its active site. The R1-1 ethyl-substituted guanidine
      N(eta) was further identified as the methylation site via mass spectrometry.
      Although weak inhibitors of CARM1, R1-1, -2, -3, and -4 are potent inhibitors of
      PRMT1 and PRMT6. These peptides are more potent against PRMT1 than product
      inhibitor peptides, showing that N(eta)-substituted arginyl peptides do not work
      by a purely product inhibitor mechanism. A trend of increasing potency with an
      increase in the number of fluorine atoms is observed for PRMT1, which may result
      from the corresponding change in the guanidino dipole moment. Modeling of the
      ethyl-arginine moiety of the R1-1 peptide demonstrates that the active site of
      PRMT1 accommodates such modifications. N(eta)-Substituted arginyl peptides
      represent lead compounds for the further development of inhibitors that target
      the methyl-acceptor binding site of PRMTs.

PMID- 20701329
TI  - Excitons and disorder in molecular nanotubes: a 2D electronic spectroscopy study
      and first comparison to a microscopic model.
AB  - The efficiency of natural light-harvesting complexes relies on delocalization and
      directed transfer of excitation energy on spatially well-defined arrangements of
      molecular absorbers. Coherent excitation delocalization and long-range molecular
      order are also central prerequisites for engineering energy flows in bioinspired
      devices. Double-wall cylindrical aggregates have emerged as excellent candidates
      that meet these criteria. So far, the experimental signatures of exciton
      relaxation in these tubular supramolecules could not be linked to models
      encompassing their entire spatial structure. On the basis of the power of two
      dimensional electronic spectroscopy, we characterize the motion of excitons in
      the three-fold band structure of the bitubular aggregate C8S3 through temporal,
      energetic, and spatial attributes. Accounting for intra- as well as interwall
      electronic interactions in the framework of a Frenkel exciton basis, we employ
      numerical computations using inhomogeneous and homogeneous microscopic models.
      The calculations on large but finite structures identify disorder-induced
      effects, which become increasingly relevant for higher energy states and give
      insight into the topology of the excited state manifold. Calculations in the
      infinite homogeneous limit capture the phenomena evidenced in the experimental
      two-dimensional patterns. Our results provide a basis for understanding recently
      reported correlated fluctuations of excitonic absorption bands and interband
      coherences in tubular aggregates.

PMID- 20701330
TI  - New generalization of supersymmetric quantum mechanics to arbitrary
      dimensionality or number of distinguishable particles.
AB  - We present here a new approach to generalize supersymmetric quantum mechanics to
      treat multiparticle and multidimensional systems. We do this by introducing a
      vector superpotential in an orthogonal hyperspace. In the case of N
      distinguishable particles in three dimensions this results in a vector
      superpotential with 3N orthogonal components. The original scalar Schrodinger
      operator can be factored using a 3N-component gradient operator and introducing
      vector "charge" operators: Q(1) and Q(1)(dagger). Using these operators, we can
      write the original (scalar) Hamiltonian as H(1) = Q(1)(dagger) x Q(1) +
      E(0)((1)), where E(0)((1)) is the ground-state energy. The second sector
      Hamiltonian is a tensor given by H(2) = Q(1)Q(1)(dagger) + E(0)((1)) and is
      isospectral with H(1). The vector ground state of sector 2, psi(0)((2)), canbe
      used with the charge operator Q(1)(dagger) to obtain the excited-state wave
      function of the first sector. In addition, we show that H(2) can also be factored
      in terms of a sector 2 vector superpotential with components W(2j) = -(partial
      partial differential ln psi(0j)((2)))/partial partial differentialx(j). Here
      psi(0j)((2)) is the jth component of psi(0)((2)). Then one obtains charge
      operators Q(2) and Q(2)(dagger) so that the second sector Hamiltonian can be
      written as H(2) = Q(2)(dagger)Q(2) + E(0)((2)). This allows us to define a third
      sector Hamiltonian which is a scalar, H(3) = Q(2) x Q(2)(dagger) + E(0)((2)).
      This prescription continues with the sector Hamiltonians alternating between
      scalar and tensor forms, both of which can be treated by the variational method
      to obtain approximate solutions to both scalar and tensor sectors. We demonstrate
      the approach with examples of a pair of separable 1D harmonic oscillators and the
      example of a nonseparable 2D anharmonic oscillator (or equivalently a pair of
      coupled 1D oscillators). We consider both degenerate and nondegenerate cases. We
      also present a generalization to arbitrary curvilinear coordinate systems in the
      Appendix.

PMID- 20701331
TI  - Oscillons localized inside breathing periodical structures in a two-variable
      model of a one-dimensional infinite excitable reaction-diffusion system.
AB  - A two-variable model of a one-dimensional (1D), infinite, excitable, reaction
      diffusion system describing oscillons localized inside an expanding breathing
      periodical structure emitting traveling impulses is presented. The model is based
      on two coupled catalytic (enzymatic) reactions.

PMID- 20701332
TI  - Ethanol monomers and dimers revisited: a Raman study of conformational
      preferences and argon nanocoating effects.
AB  - The gauche-trans conformational distribution in ethanol can be determined from
      the OH stretching Raman spectrum of seeded supersonic jet expansions, which thus
      provides a sensitive conformational thermometer. Depending on the rare gas
      mixture, one, two or four ethanol dimer conformations are abundant. Their
      conformational assignment is facilitated by the observation of hydrogen bond
      acceptor modes, which have similar Raman cross sections but much inferior
      infrared intensities than donor modes. Ethanol monomers and dimers can be
      progressively Ar-coated, and the resulting spectra may be compared with those in
      a bulk argon matrix. The low frequency range of torsional transitions provides
      some evidence for conformation-changing transitions in Raman jet spectra.

PMID- 20701333
TI  - Mass-spectroscopic observations of glycine subjected to strong shock loading.
AB  - We have made time-of-flight mass-spectroscopic observations of 85/15 wt %
      water/glycine solutions and of crystalline alpha-glycine subjected to strong
      shock loading. The shockwaves were produced by placing the materials in contact
      with detonating solid explosives. In the solution observations, we have done
      experiments with glycine molecules composed of ordinary isotopes and with
      molecules labeled with (13)C, (15)N, and D atoms. The primary reason for
      conducting this research was to examine whether glycine molecules can survive
      exposure to strong shock loading, e.g., as might occur in the entry of a meteor
      into the earth's atmosphere. Our results show that glycine molecules can
      withstand the rigors of shock environments that generate pressure and temperature
      up to 180 kbar and 3200 K. Glycine in a 85 H(2)O/15 glycine wt % solution (i.e.,
      one molecule of glycine to ca. 24 H(2)O molecules) exists primarily in its
      zwitterionic form. In both the solution and crystal experiments, we observed
      zwitterionic dimers, trimers, and, possibly, tetramers, after the materials were
      shocked. This implies that the solvating water molecules in the solution
      experiments must reside on the exterior of groups of solvated glycine molecules.
      We report quantum-chemical calculations, using density functional theory, that
      predict that two glycine zwitterions are bound together by ca. 15.72 kcal when
      immersed in an Onsager model of water. Our observations allow us to place lower
      bound estimates on the lifetime of glycine zwitterions under our conditions. We
      have examined our data to determine whether dipeptide formation has occurred and
      found no evidence that it has. Compressible fluid-mechanical calculations were
      performed to estimate the pressures, temperatures, and the time scales present in
      the experiments.

PMID- 20701334
TI  - Experimental and theoretical investigation of the self-reaction of phenyl
      radicals.
AB  - A combination of experiment and theory is applied to the self-reaction kinetics
      of phenyl radicals. The dissociation of phenyl iodide is observed with both time
      of-flight mass spectrometry, TOF-MS, and laser schlieren, LS, diagnostics coupled
      to a diaphragmless shock tube for temperatures ranging from 1276 to 1853 K. The
      LS experiments were performed at pressures of 22 +/- 2, 54 +/- 7, and 122 +/- 6
      Torr, and the TOF-MS experiments were performed at pressures in the range 500-700
      Torr. These observations are sensitive to both the dissociation of phenyl iodide
      and to the subsequent self-reaction of the phenyl radicals. The experimental
      observations indicate that both these reactions are more complicated than
      previously assumed. The phenyl iodide dissociation yields approximately 6%
      C(6)H(4) + HI in addition to the major and commonly assumed C(6)H(5) + I channel.
      The self-reaction of phenyl radicals does not proceed solely by recombination,
      but also through disproportionation to benzene + o-/m-/p-benzynes, with
      comparable rate coefficients for both. The various channels in the self-reaction
      of phenyl radicals are studied with ab initio transition state theory based
      master equation calculations. These calculations elucidate the complex nature of
      the C(6)H(5) self-reaction and are consistent with the experimental observations.
      The theoretical predictions are used as a guide in the development of a model for
      the phenyl iodide pyrolysis that accurately reproduces the observed laser
      schlieren profiles over the full range of the observations.

PMID- 20701335
TI  - Vibronic analysis of the S1-S0 transition of phenylacetylene using photoelectron
      imaging and spectral intensities derived from electronic structure calculations.
AB  - The vibrational structure of the S(1)-S(0) electronic band of phenylacetylene has
      been recorded by 1 + 1 resonance-enhanced multiphoton ionization, accompanied by
      slow electron velocity map imaging photoelectron spectroscopy at each resonant
      vibrational band. Assignments of the S(1) vibrations (up to 2000 cm(-1) above the
      band origin) are based upon the relative intensities of the vibronic bands
      calculated by complete second-order vibronic coupling, vibration-rotation
      (Coriolis and Birss) coupling calculations, and the vibrational structure of the
      S(1) resonant photoelectron spectra. Although this is an allowed electronic
      transition, the relative intensities of the a(1) bands are often largely
      determined by vibronic coupling rather than simple Franck-Condon factors, and
      second-order coupling is substantial. Nonsymmetric vibrations have intensities
      obtained through either vibronic or Coriolis coupling, and the calculations have
      been instrumental in discriminating between alternate possibilities in the
      assignments. Strong vibronic effects are expected to be present in the spectra of
      most monosubstituted benzenes, and the calculations presented here show that
      theoretical treatments based upon electronic structure calculations will
      generally be useful in the analysis of their spectra.

PMID- 20701336
TI  - Theoretical validation of chemical kinetic mechanisms: combustion of methanol.
AB  - A new technique is proposed that uses theoretical methods to systematically
      improve the performance of chemical kinetic mechanisms. Using a screening method,
      the chemical reaction steps that most strongly influence a given kinetic
      observable are identified. The associated rate coefficients are then improved by
      high-level quantum chemistry and transition-state-theory calculations, which
      leads to new values for the coefficients and smaller uncertainty ranges. This
      updating process is continued as new reactions emerge as the most important steps
      in the target observable. The screening process employed is a global sensitivity
      analysis that involves Monte Carlo sampling of the full N-dimensional uncertainty
      space of rate coefficients, where N is the number of reaction steps. The method
      is applied to the methanol combustion mechanism of Li et al. (Int. J. Chem.
      Kinet. 2007, 39, 109.). It was found that the CH(3)OH + HO(2) and CH(3)OH + O(2)
      reactions were the most important steps in setting the ignition delay time, and
      the rate coefficients for these reactions were updated. The ignition time is
      significantly changed for a broad range of high-concentration methanol/oxygen
      mixtures in the updated mechanism.

PMID- 20701337
TI  - Quantum chemical study of the acrolein (CH2CHCHO) + OH + O2 reactions.
AB  - Acrolein, a beta-unsaturated (acrylic) aldehyde, is one of the simplest
      multifunctional molecules, containing both alkene and aldehyde groups. Acrolein
      is an atmospheric pollutant formed in the photochemical oxidation of the
      anthropogenic VOC 1,3-butadiene, and serves as a model compound for methacrolein
      (MACR) and methyl vinyl ketone (MVK), the major oxidation products of the
      biogenic VOC isoprene. In addition, acrolein is involved in combustion and
      biological oxidation processes. This study presents a comprehensive theoretical
      analysis of the acrolein + OH + O(2) addition reactions, which is a key
      photochemical oxidation sequence, using the G3SX and CBS-QB3 theoretical methods.
      Both ab initio protocols provide relatively similar results, although the CBS-QB3
      method systematically under-predicts literature heats of formation using
      atomization enthalpies, and also provides lower transition state barrier heights.
      Several new low-energy pathways for unimolecular reaction of the acrolein-OH-O(2)
      radicals are identified, with energy at around or below that of the acrolein-OH
      isomers + O(2). In each case these novel reactions have the potential to reform
      the hydroxyl radical (OH) and form coproducts that include glyoxal,
      glycolaldehyde (HOCH(2)CHO), formaldehyde (HCHO), CO, and substituted epoxides.
      Analogous reaction schemes are developed for the photochemical oxidation of MACR
      and MVK, producing a number of observed oxidation products. The reaction MACR +
      OH + O(2) --> hydroxyacetone + OH + CO is expected to be of particular
      importance. This study also proposes that O(2) addition to chemically activated
      acrolein-OH adducts can provide prompt regeneration of OH in the atmospheric
      oxidation of acrolein, via a double activation mechanism. This mechanism can also
      be extended to isoprene, MVK, and MACR. The importance of the novel chemistry
      revealed here in the atmospheric oxidation of acrolein and other structurally
      related OVOCs and VOCs requires further investigation. Additionally, a critical
      evaluation of the acrolein heat of formation is presented, and a new value of 
      16.7 +/- 1.0 kcal mol(-1) is recommended along with other thermochemical
      properties, from a W1 level calculation.

PMID- 20701338
TI  - High-temperature measurements and a theoretical study of the reaction of OH with
      1,3-butadiene.
AB  - The reaction of hydroxyl (OH) radicals with 1,3-butadiene (C(4)H(6)) was studied
      behind reflected shock waves over the temperature range 1011-1406 K and at
      pressures near 2.2 atm. OH radicals were produced by shock-heating tert-butyl
      hydroperoxide, (CH(3))(3)-CO-OH, and were monitored by narrow line width ring dye
      laser absorption of the well-characterized R(1)(5) line of the OH A-X (0,0) band
      near 306.7 nm. OH time histories were modeled using a comprehensive 1,3-butadiene
      oxidation mechanism, and rate constants for the reaction of OH with 1,3-butadiene
      were extracted by matching modeled and measured OH concentration time histories.
      Detailed error analyses yielded an uncertainty estimate of +/-13% at 1200 K for
      the rate coefficient of the target reaction. The current data extends the
      temperature range of the only previous high-temperature study for this reaction.
      The rate coefficient and the branching fractions for the H-abstraction channels
      of the target reaction were also calculated over the temperature range 250-2500 K
      using variational transition-state theory based on QCISD(T)/cc
      pVinfinityZ//B3LYP/6-311++G(d,p) quantum chemistry. The calculations are in good
      agreement with the experimental results above 1200 K.

PMID- 20701339
TI  - Infrared-optical double resonance spectroscopic measurements on 2-(2'
      pyridyl)benzimidazole and its hydrogen bonded complexes with water and methanol.
AB  - The H(2)O and MeOH complexes of 2-(2'-pyridyl)benzimidazole (2PBI) were
      investigated using laser induced fluorescence and IR-UV double resonance
      spectroscopic techniques. The 0(0)(0) band for the S(1) <-- S(0) electronic
      transition of 2PBI was observed at 31,616 cm(-1), and corresponding transitions
      for the H(2)O and MeOH complexes show substantial red shifts of 1059 and 1203 cm(
      1), respectively. A long progression up to v' = 5 in the 92 cm(-1) vibrational
      mode was observed for bare 2PBI, which is considerably shortened to v' = 2 and v'
      = 1 for the H(2)O and MeOH complexes, respectively. The combined experimental and
      theoretical results suggest that both H(2)O and MeOH form cyclic complex with
      2PBI incorporating N-H...O and O-H...N hydrogen bonds. Comparison with other
      known hydrogen-bonded H(2)O complexes of bifunctional aza-heteroaromatic
      molecules suggest that 2PBI-H(2)O is probably one of the strongest of all known
      complexes. Further, the experimental data in combination with calculations
      suggests that the hydrogen atom/proton transfer leading to tautomeric form might
      be thermodynamically spontaneous in the electronic excited state, due to explicit
      solvent (H(2)O and MeOH) participation.

PMID- 20701340
TI  - Mechanistic insights into Cu(I)-catalyzed azide-alkyne "click" cycloaddition
      monitored by real time infrared spectroscopy.
AB  - A designed ligand-accelerated Cu(I)-catalyzed cycloaddition (CuAAC) reaction was
      monitored for the first time by real time infrared analysis technique based on
      ATR-FTIR principles. Principal components analysis (PCA) and two-dimensional
      correlation spectroscopy (2Dcos) results showed that the consumption of alkyne
      and azide took place successively followed by the formation of the product 1,2,3
      triazole, and a 1:1 complex of two reactants would be formed in the reaction
      process. The rate-determining step of the CuAAC reaction was also experimentally
      confirmed for the first time to be the transition of azide-alkyne 1:1 complex to
      the preproduct 1,2,3-triazole. Our results are in good conformity with the
      current catalytic mechanism proposed by Sharpless et al. according to DFT
      calculation results.

PMID- 20701341
TI  - Hydrogen bonding to multifunctional molecules: spectroscopic and ab initio
      investigation of 4-ethynylbenzonitrile-(water)(1-3) complexes.
AB  - The water complexes of 4-ethynylbenzonitrile (4EBzN) were investigated with IR-UV
      double resonance spectroscopy. Water interacts with the pi electron density of
      the C[triple bond]N group in 4EBzN, leading to the formation of a quasiplanar
      cyclic complex incorporating C-H...O and O-H...pi hydrogen bonds. The (H(2)O)(2)
      and (H(2)O)(3) complexes of 4EBzN are characterized by the presence of hydrogen
      bonding bridges between the hydrogen bond donor (aromatic C-H group) and acceptor
      (C[triple bond]N group) sites present in 4EBzN. The present structures of the
      water complexes are similar to the corresponding complexes of benzonitrile but
      are drastically different from water complexes of phenylacetylene and
      fluorophenylacetylenes. The infrared spectra in the O-H stretching region
      indicate that the stability of all the water complexes of 4EBzN is lower than
      that of the corresponding complexes of benzonitrile, which can be attributed to
      the mild electron withdrawing ability of the ethynyl group present in the para
      position relative to the nitrile group. Hierarchally, the C[triple bond]N group
      has the higher propensity to form hydrogen bonding relative to the acetylenic
      group and the benzene ring in 4EBzN.

PMID- 20701342
TI  - Infrared spectra of dimethylquinolines in the gas phase: experiment and theory.
AB  - Infrared spectra of atmospherically important dimethylquinolines (DMQs), namely
      2,4-DMQ, 2,6-DMQ, 2,7-DMQ, and 2,8-DMQ in the gas phase at 80 degrees C were
      recorded using a long variable path-length cell. DFT calculations were carried
      out to assign the bands in the experimentally observed spectra at the B3LYP/6
      31G* level of theory. The spectral assignments particularly for the C-H
      stretching modes could not be made unambiguously using calculated anharmonic or
      scaled harmonic frequencies. To resolve this problem, a scaled force field method
      of assignment was used. Assignment of fundamental modes was confirmed by
      potential energy distributions (PEDs) of the normal modes derived by the scaled
      force fields using a modified version of the UMAT program in the QCPE package. We
      demonstrate that for large molecules such as the DMQs, the scaling of the force
      field is more effective in arriving at the correct assignment of the fundamentals
      for a quantitative vibrational analysis. An error analysis of the mean deviation
      of the calculated harmonic, anharmonic, and force field fitted frequencies from
      the observed frequency provides strong evidence for the correctness of the
      assignment.

PMID- 20701343
TI  - Effect of magnesium cation on the interfacial properties of aqueous salt
      solutions.
AB  - Sodium chloride solutions have been used extensively as a model of seawater in
      both theoretical and experimental studies of the chemistry of sea salt aerosol.
      Many groups have found that chloride anions are present at the air-solution
      interface. This observation has been important for the development of a mechanism
      for the heterogeneous production of molecular chlorine from chloride in sea salt
      aerosol. However, while sodium chloride is a major constituent of seawater, it is
      by no means the only salt present. Seawater contains one Mg(2+) for every eight
      Na(+). Mg(2+) is naturally occurring in ocean waters from mineral deposits in the
      Earth's crust and biological sources. Mg(2+) forms a hexahydrate structure,
      rather than contact ion pairs with chloride anion, and this impacts the ordering
      of water in solution. In this study, we use molecular dynamics simulations, ab
      initio calculations, and vibrational sum frequency generation (SFG) spectroscopy
      to explore the effect of the Mg(2+) cation and its tightly bound solvation shell
      on the surface propensity of chloride, ion-ion interactions, and water structure
      of the air-solution interface of concentrated chloride salt solutions. In
      addition, we provide molecular level details that may be relevant to the
      heterogeneous reactions of chloride in deliquesced sea salt aerosols. In
      particular, we show that the presence of the divalent Mg(2+) cation does not
      modify the surface propensity of chloride compared to Na(+) and hence, its
      availability to interfacial reaction, although some differences in the behavior
      of chloride may occur due to specific ion interactions. In this work, we also
      discuss the SFG free OH band at the surface of salt solutions and conclude that
      it is often not straightforward to interpret.

PMID- 20701344
TI  - Kinetics of the reactions of Cl atoms with several ethers.
AB  - The reactions of Cl with tetrahydrofuran, tetrahydropyran, and dimethyl ether
      have been studied as a function of temperature, pressure, and O(2) concentration.
      The temperature was varied from approximately 280 to 360 K, the mole fraction of
      O(2) ranged from zero to approximately 0.6, and the experiments were made in a
      bath of argon at total pressures ranging from approximately 300 to 760 Torr. The
      rate coefficients were measured using the relative rate method with gas
      chromatographic analysis. The reaction of Cl with isobutane was the reference
      reaction, the rate coefficients for which were calibrated against the reaction of
      propane with chlorine atoms as a function of temperature. The rate coefficients
      were unaffected by the concentration of O(2) or by variation in pressure. The
      rate coefficient for the reaction of Cl with isobutane increased slightly with
      decreasing temperature. This weak temperature dependence of the rate coefficient
      was in satisfactory agreement with information in the literature and is
      represented in Arrhenius form by k(T) = (1.02(-0.25)(+0.32)) x 10(-10) exp(99 +/-
      88/T) cm(3) molecule(-1) s(-1), where the uncertainties represent two standard
      deviations. The rate coefficients for the reactions of Cl with the ethers did not
      show a statistically significant dependence on temperature. Their average values
      over our range of temperature are: for Cl + tetrahydrofuran, k = (2.71 +/- 0.34)
      x 10(-10) cm(3) molecule(-1) s(-1); for Cl + tetrahydropyran, k = (2.03 +/- 0.82)
      x 10(-10) cm(3) molecule(-1) s(-1); and for Cl + dimethyl ether, k = (1.73 +/-
      0.22) x 10(-10) cm(3) molecule(-1) s(-1), in which the uncertainties are again
      two standard deviations.

PMID- 20701345
TI  - Kinetics and products of gas-phase reactions of ozone with methyl methacrylate,
      methyl acrylate, and ethyl acrylate.
AB  - The kinetics and products of the gas-phase reactions of ozone with methyl
      methacrylate, methyl acrylate, and ethyl acrylate have been investigated at 760
      Torr total pressure of air and 294 +/- 2 K. The rate coefficients obtained (in
      cm(3) molecule(-1) s(-1) units) were as follows: k(methyl methacrylate) = (6.7 +/
      0.9) x 10(-18), k(methyl acrylate) = (0.95 +/- 0.07) x 10(-18), and k(ethyl
      acrylate) = (1.3 +/- 0.1) x 10(-18). In addition to formaldehyde being observed
      as a product of the three reactions, the other major reaction products were
      methyl pyruvate from reaction of ozone with methyl methacrylate, methyl
      glyoxylate from reaction of ozone with methyl acrylate, and ethyl glyoxylate from
      reaction of ozone with ethyl acrylate. Possible reaction mechanisms leading to
      the observed products are presented and discussed.

PMID- 20701346
TI  - Photolysis of glycolaldehyde in the 280-340 nm region.
AB  - We have investigated the gas-phase UV photolysis of glycolaldehyde (HOCH(2)CHO)
      by laser photolysis combined with cavity ring-down spectroscopy. Absorption cross
      sections of glycolaldehyde in the 280-340 nm region were measured by cavity ring
      down spectroscopy. The HCO + CH(2)OH and the OH + CH(2)CHO product channels
      following the photolysis of glycolaldehyde were directly examined. The average
      HCO quantum yields from the glycolaldehyde photolysis were 0.61 +/- 0.08, 0.59 +/
      0.05, 0.61 +/- 0.16, 0.66 +/- 0.09, 0.61 +/- 0.11, 0.65 +/- 0.05, 0.47 +/- 0.04,
      0.52 +/- 0.09, and 0.45 +/- 0.05 at 280, 285, 290, 295, 300, 305, 308, 310, and
      315 nm, where the error quoted (1sigma) represents experimental scatter. The
      average OH quantum yield from the photolysis of glycolaldehyde at 308 nm was 0.11
      +/- 0.02, where the error quoted (1sigma) represents measurement uncertainty. End
      products such as CO, H(2)CO, (CHO)(2), CH(3)OH, HCOOH, and CO(2) were detected
      from the 308 nm photolysis of glycolaldehyde. The yields of CO, H(2)CO, (CHO)(2),
      CH(3)OH, and HCOOH were estimated. We also directly measured the rate constant
      for the reaction between the OH radical and glycolaldehyde. The rate constant
      obtained was (1.01 +/- 0.20) x 10(-11) cm(3) molecule(-1) s(-1), where the error
      quoted (1sigma) represents measurement uncertainty. Atmospheric implications of
      the results are discussed.

PMID- 20701347
TI  - Hydroxyl-radical-induced degradative oxidation of beta-lactam antibiotics in
      water: absolute rate constant measurements.
AB  - The beta-lactam antibiotics are some of the most prevalent pharmaceutical
      contaminants currently being detected in aquatic environments. Because the
      presence of any trace level of antibiotic in water may adversely affect aquatic
      ecosystems and contribute to the production of antibiotic-resistant bacteria,
      active removal by additional water treatments, such as using advanced oxidation
      and reduction processes (AO/RPs), may be required. However, to ensure that any
      AOP treatment process occurs efficiently and quantitatively, a full understanding
      of the kinetics and mechanisms of all of the chemical reactions involved under
      the conditions of use is necessary. In this study, we report on our kinetic
      measurements for the hydroxyl-radical-induced oxidation of 11 beta-lactam
      antibiotics obtained using electron pulse radiolysis techniques. For the 5-member
      ring species, an average reaction rate constant of (7.9 +/- 0.8) x 10(9) M(-1) s(
      1) was obtained, slightly faster than for the analogous 6-member ring containing
      antibiotics, (6.6 +/- 1.2) x 10(9) M(-1) s(-1). The consistency of these rate
      constants for each group infers a common reaction mechanism, consisting of the
      partitioning of the hydroxyl radical between addition to peripheral aromatic
      rings and reaction with the central double-ring core of these antibiotics.

PMID- 20701348
TI  - Observations of high-density ferroelectric ordered water in kaolinite trenches
      using Monte Carlo simulations.
AB  - Grand canonical Monte Carlo simulations are employed to investigate the structure
      of water adsorbed on kaolinite surfaces with trenchlike defects. The results
      obtained for two water models (SPC/E and TIP5P-E) at 235 K are essentially the
      same. Calculation of water density profiles in all three dimensions shows that a
      dense ordered state is present in our trench systems. The narrowest trenches have
      the highest water density and display clearly layered structures along the width
      and depth of a trench. The water within a trench shows distinct proton order and
      is strongly ferroelectric. These ordered structures might be important in the
      initial stages of nucleation and growth of ice on kaolinite surfaces.

PMID- 20701349
TI  - Hydrates of Cu2+ and CuCl+ in dilute aqueous solution: a density functional
      theory and polarized continuum model investigation.
AB  - In this work, structures, and properties of Cu(2+) and CuCl(+) hydrates in the
      gas and aqueous phases have been investigated using the B3LYP method. Contact ion
      pair (CIP) and solvent-shared ion pair (SSIP) were both taken into account for
      CuCl(+) hydrates. Our calculations show that [Cu(H(2)O)(n)](2+) clusters favor a
      very open four-coordinated structure for n = 5-12 in the gas phase, while a five
      coordinated conformer is favored for n > or = 8 in the aqueous phase. An
      approximate complete solvation shell of Cu(2+) in the aqueous phase needs more
      than 12 water molecules, while that of CuCl(+) in the aqueous phase needs only
      about eight water molecules. For [CuCl(H(2)O)(n)](+) clusters, the most stable
      structure is a four-coordinated CIP conformer for n = 4-7 in the gas phase and a
      five-coordinated CIP conformer for n = 8-10 in the aqueous phase. However, the
      five-coordinated CIP/h conformer (CIP conformer that the axial chloride atom
      tends to dissociate) of [CuCl(H(2)O)(n)](+) clusters becomes more favorable as n
      increases to 11. As the hydration process proceeds, the charges on the copper
      atom of [Cu(H(2)O)(n)](2+) clusters decrease, while those of [CuCl(H(2)O)(n)](+)
      clusters increase (probably due to the dissociation of Cl(-)). The d-d electron
      transition and partial charge transition band around 160 nm of the five
      coordinated conformer of [Cu(H(2)O)(n)](2+) clusters and those bands
      (approximately 170 and approximately 160 nm) of SSIP or five-coordinated CIP/h
      conformers of [CuCl(H(2)O)(n)](+) clusters are coincident with the absorption of
      [Cu](2+)(aq) species (approximately 180 nm) resolved from the spectra obtained in
      trace CuCl(2) (ca. 10(-5) mol x kg(-1)) + LiCl (0-18 mol x kg(-1)) aqueous
      solution, while those of five-coordinated CIP conformers of [CuCl(H(2)O)(n)](+)
      clusters (n = 8 and 9) around 261 and 247 nm correspond to the absorption of
      [CuCl](+)(aq) species (approximately 250 nm). Our calculated electronic spectra
      indicate that the typical peak of copper(II)-chloride complexes changes from 180
      to 250 nm, and 275 nm, as the process of Cl(-) coordination. For [Cu](2+)(aq),
      [CuCl](+)(aq), and [CuCl(2)](0)(aq) species, the central Cu(II) atom prefers five
      coordination.

PMID- 20701350
TI  - Magnetic properties of Cu(m)O(n) clusters: a first principles study.
AB  - Experimental evidence shows that small Cu(2)O nanoparticles exhibit ferromagnetic
      or paramagnetic properties, allowing for the promising possibility to recycle the
      catalyst Cu(2)O easily in wastewater treatment. In this paper, theoretical
      calculation studying the magnetic property of copper/oxide clusters is reported.
      A series of Cu(m)O(n) ((m, n) = (4, 1); (4, 2); (4, 5); (16, 15); (28, 15); (44,
      15); (28, 27)) clusters were investigated using generalized gradient
      approximation (GGA) and the Hubbard U (GGA+U) method within density functional
      theory (DFT). It is found that the electronic structures of bulk Cu(2)O
      calculated by the GGA and GGA+U are similar. The structures of Cu(m)O(n) ((m, n)
      = (4, 1); (4, 2); (4, 5)) are all planar. For the bulk-product Cu(m)O(n) ((m, n)
      = (16, 15); (28, 15); (44, 15); (28, 27)), O atoms prefer to be the outermost
      atoms. We classified two types of clusters on the basis of their O to Cu atomic
      ratios. One is O-rich clusters, i.e., Cu(4)O(5), Cu(16)O(15), and Cu(28)O(27).
      The other is O-poor clusters, i.e., Cu(4)O, Cu(4)O(2), Cu(28)O(15), and
      Cu(44)O(15). The calculation results show that the O-rich clusters have longer
      average Cu-Cu bonds and larger binding energy than those of the O-poor ones. More
      interestingly, the former are magnetic and give ferromagnetic ordering while the
      latter are nonmagnetic. The hydrogenation of O-terminated clusters can improve
      its stability but suppress its magnetism. The study may be extremely useful for
      the potential applications of Cu(2)O nanoparticles in the catalysis and
      semiconductor fields.

PMID- 20701351
TI  - Theoretical insights into branched and fused expanded pyridiniums by the means of
      density functional theory.
AB  - With the aim of getting insights into the peculiar electronic, structural, and
      photophysical properties of four expanded pyridinium systems of potential use as
      electron acceptors in supramolecular architectures, their electronic and
      geometrical structures, at both the ground and the excited states, were
      investigated by the means of density functional theory (DFT) and time-dependent
      DFT (TD-DFT). Solvent effects were included by the means of a polarizable
      continuum model (PCM) at both the ground and the excited states. In particular,
      the computed photophysical behaviors (absorption and emission) of the fused
      architectures were compared to those of the respective branched precursors in
      order to clarify the origin(s) of (i) the extension of their electronic
      absorption toward the visible region and (ii) the increase of their luminescence
      quantum yields and red-shifted emission wavelengths experimentally observed. The
      theoretical insights gained allow for a clear-cut explanation of the different
      behavior of these systems of interest as electron acceptors and luminophores for
      more complex supramolecular architectures and opens the route for a joint
      experimental and theoretical design of new pyridinium-based acceptors.

PMID- 20701352
TI  - First-principles calculations for the H center in SrF2 crystals.
AB  - The ground state of H-center systems for the SrF(2) crystal is simulated with two
      different arrangements, which are oriented along either [100] or [111] axes. The
      calculations are based on hybrid Hartree-Fock and density functional theory
      exchange functionals by using Becke's three-parameter method combined with the
      nonlocal correlation functionals of Perdew and Wang. The energy difference
      between H centers with different orientations shows that the H center oriented in
      the [111] direction in alkaline earth fluorides is the most stable configuration.
      The geometric relaxations of the neighboring atoms surrounding the H centers are
      presented. The combination energy of an H center and the formation energy of the
      related F-H pair in both alkaline earth fluorides are discussed. We report also
      the electronic structure of the H center systems. The effective charges and spins
      of the substitutional and interstitial fluorine atoms show that the hole is
      located at the interstitial fluorine in the system with the [111] orientation of
      the H center. The band structures are illustrated. With the help of studying the
      total and partial density of states, the constituents of the defect bands are
      clarified.

PMID- 20701353
TI  - Absorption oscillator strengths for vibronic transitions of nppi Rydberg series
      in NO.
AB  - The vibronic intensities for band systems of NO corresponding to transitions with
      origin in both the X(2)Pi ground and the 3ssigma(A(2)Sigma(+)) Rydberg states,
      and ending in the nppi Rydberg series with n = 3-5, have been determined. The
      description of the Rydberg states has been made with the molecular quantum defect
      orbital methodology. The Rydberg-valence interaction of the (2)Pi symmetry states
      involved in the studied transitions has been analyzed through a vibronic matrix.
      The present results have been compared with experimental and theoretical data
      available in the literature. Additionally, predictions for a number of unknown
      intensities have been made, which may be useful for the interpretation of the
      spectrum of NO.

PMID- 20701354
TI  - Dihydrogen bond cooperativity in aza-borane derivatives.
AB  - A theoretical study of the dihydrogen-bonded clusters of three aza-borane
      derivatives, H-N....B-H, has been carried out using DFT, M05-2X, computational
      methods. Clusters consisting of up to 10 monomers have been considered. The
      energetic results show an increment of the average interaction energy per monomer
      as the size of the cluster increases. Similarly, a shortening of the
      intermolecular distances up to 0.1 A is observed. Among the electrostatic
      properties, an increment of the dipole moment and the absolute values of the
      molecular electrostatic potential at the interacting point of the cluster are
      observed. Finally, the orbital interaction responsible for the dihydrogen bond
      follows the same pattern observed for the bond distances. Thus, it can be
      concluded that these systems show behavior, with respect to cooperativity,
      similar to those observed in standard hydrogen bonds.

PMID- 20701355
TI  - Ab initio study of ternary complexes A...NCH...C with A,C = HCN, HF, HCl, ClF,
      and LiH: energetics and spin-spin coupling constants across intermolecular bonds.
AB  - A systematic ab initio study has been carried out to investigate the structures,
      binding energies, and spin-spin coupling constants of binary complexes A...NCH
      and NCH...C and ternary complexes A...NCH...C for A,C = HCN, HF, HCl, FCl, and
      HLi. These complexes are stabilized by some combination of hydrogen bonds,
      dihydrogen bonds, halogen bonds, and lithium bonds. The binding energies of the
      ternary complexes are enhanced relative to those of the corresponding binary
      complexes, suggesting that A...NCH is a stronger proton-donor acid and NCH...C is
      a stronger base relative to the isolated monomer HCN. The ternary complexes with
      the largest enhancement energies are FH...NCH...HLi, HLi...NCH...NCH, and
      HLi...NCH...HLi, each containing molecules with large dipole moments, and each
      with a linear head-to-tail arrangement of dipole moment vectors. The equation-of
      motion coupled-cluster single and doubles method (EOM-CCSD) has been employed to
      evaluate spin-spin coupling constants across intermolecular bonds for binary
      complexes A...NCH and NCH...C and for ternary complexes A...NCH...C. These data
      are used to investigate how the presence of C influences coupling constants
      associated with the A...NCH interaction, and how the presence of A influences
      coupling constants for the NCH...C interaction. Changes in coupling constants in
      the ternary complexes relative to the binary may be related to the binding
      energies of corresponding binary complexes and the enhanced binding energies of
      the ternary complexes. Two-bond coupling constants across X-H...Y hydrogen bonds
      [(2h)J(X-Y)] are related to changes in intermolecular distances.

PMID- 20701356
TI  - Nonlinear optical properties of flavylium salts: a quantum chemical study.
AB  - Ab initio calculations have been carried out to unravel the relationships between
      the structure and the first hyperpolarizability in flavylium derivatives, with
      the aim to design efficient second-order nonlinear optical (NLO) switching
      compounds. Large contrasts of the first hyperpolarizability have been obtained
      along the pH-controlled and photoinduced transformations for specific
      combinations of chemical substituents in the 4'- and 7-positions, which
      demonstrates that these multistate systems should behave as highly efficient
      molecular NLO switches.

PMID- 20701357
TI  - Stereoelectronic effects in alpha-carbanions of conformationally constrained
      sulfides, sulfoxides, and sulfones.
AB  - Stabilizing effects in oxygenated thiane- and 1,3-dithiane-derived alpha
      carbanions were investigated computationally. All isomers bearing sulfide,
      sulfoxide, and sulfone functional groups and combinations thereof were
      investigated by DFT calculations and NBO analyses. Their stabilities and the
      stereoelectronic effects present in these compounds were compared. Stabilizing
      effects of the respective functional groups were further estimated by calculation
      of isodesmic reactions. It turned out that n(C) --> sigma*(S-O) interactions,
      where both the n(C) and the S=O bond are in an antiperiplanar conformation, have
      the highest stabilizing effects. Similar stabilizing interactions are effective
      in carbanions with an equatorial lone pair at the carbon; here a productive n(C) 
      -> sigma*(S-C) interaction is possible. n(C) --> sigma*(S-O) interactions, where
      the S=O bond is part of a sulfoxide are significantly more effective than in
      sulfones. Calculations of isodesmic reactions show similar trends but suggest the
      presence of additional electrostatic effects and possibly, to some extent, steric
      effects.

PMID- 20701359
TI  - Targeting of an interrupted polypurine:polypyrimidine sequence in mammalian cells
      by a triplex-forming oligonucleotide containing a novel base analogue.
AB  - The DNA triple helix consists of a third strand of nucleic acid lying in the
      major groove of an intact DNA duplex. The most stable triplexes form on
      polypurine:polypyrimidine sequences, and pyrimidine interruptions in the purine
      strand are destabilizing. Sequence stringency is imparted by specific Hoogsteen
      hydrogen bonds between third strand bases and the purine bases in the duplex.
      Appropriate base and sugar modifications of triple helix-forming oligonucleotides
      (TFOs) confer chromosome targeting activity in living cells. However, broad
      utilization of TFOs as gene targeting reagents in mammalian cells has been
      limited by the requirement for homopurine target sequences. Although there have
      been a number of base analogues described that appear to be promising as
      candidates for triplex target expansion, none has been examined in a biological
      system. We have employed a postsynthetic strategy to prepare a collection of TFOs
      with base analogues at a defined position. Following assessment of affinity for a
      triplex target with a single C:G inversion, TFOs with a second generation of
      analogues were synthesized. One of these, TFO-5a, with 2'-OMe-guanidinylethyl-5
      methylcytosine at the position corresponding to the C:G interruption in the
      target sequence, was further modified to confer bioactivity. The activity of this
      TFO, linked to psoralen, was measured in a mammalian cell line that was
      engineered by directed sequence conversion to carry a triplex target with a
      single C:G interruption. TFO-5a was active against this target and inactive
      against the corresponding target with an uninterrupted polypurine:polypyrimidine
      sequence.

PMID- 20701360
TI  - Quantitative proteomics using SILAC coupled to LC-MS/MS reveals changes in the
      nucleolar proteome in influenza A virus-infected cells.
AB  - Influenza A virus (IAV) is a major human pathogen whose genotypic diversity
      results in unpredictable pandemics and epidemics. Interaction with the cell
      nucleus is essential to IAV infection, allowing recruitment of cellular
      components to facilitate virus replication. Viral proteins are also targeted to
      the nucleolus, a subnuclear structure involved in ribosomal biogenesis, RNA
      maturation, stress response, and control of cell growth, but the functional
      consequences of this are unclear. We took an unbiased approach to studying IAV
      nucleolar interactions by using stable isotope labeling with amino acids in cell
      culture (SILAC) in conjunction with LC-MS/MS to quantify changes in the nucleolar
      proteome following infection with A/PR/8/34 (H1N1) and A/Udorn/72 (H3N2) strains
      of the virus. Only a minority of nucleolar proteins showed significant changes in
      abundance after infection; these alterations were mostly different between the
      two strains but could be validated by confocal microscopy of infected cells. Many
      of the affected proteins comprised functional groupings, including components of
      ribonuclease P, RNA polymerase I, the MLL1 histone methyltransferase complex, as
      well as nuclear paraspeckles and the RNA editing apparatus. This, as well as
      comparison with other viruses that cause changes in the nucleolar proteome,
      suggests that IAV targets specific nucleolar pathways.

PMID- 20701361
TI  - Good practices in free-energy calculations.
AB  - As access to computational resources continues to increase, free-energy
      calculations have emerged as a powerful tool that can play a predictive role in a
      wide range of research areas. Yet, the reliability of these calculations can
      often be improved significantly if a number of precepts, or good practices, are
      followed. Although the theory upon which these good practices rely has largely
      been known for many years, it is often overlooked or simply ignored. In other
      cases, the theoretical developments are too recent for their potential to be
      fully grasped and merged into popular platforms for the computation of free
      energy differences. In this contribution, the current best practices for carrying
      out free-energy calculations using free energy perturbation and nonequilibrium
      work methods are discussed, demonstrating that at little to no additional cost,
      free-energy estimates could be markedly improved and bounded by meaningful error
      estimates. Monitoring the probability distributions that underlie the
      transformation between the states of interest, performing the calculation
      bidirectionally, stratifying the reaction pathway, and choosing the most
      appropriate paradigms and algorithms for transforming between states offer
      significant gains in both accuracy and precision.

PMID- 20701362
TI  - A study of the dynamics of the branch ends of a series of pyrene-labeled
      dendrimers based on pyrene excimer formation.
AB  - A series of pyrene-labeled dendrimers were prepared from generation n = 1 to n =
      4 where the pyrenes were attached to the end groups of the dendrimers. Pyrene
      excimer formation was monitored by steady-state and time-resolved fluorescence
      spectroscopy as a function of generation number and in terms of the I(E)/I(M)
      ratio and the average rate constant of excimer formation <k>. To account for the
      unconventional distribution of pyrene labels which were neither randomly
      distributed throughout the macromolecule nor limited to just two units which are
      the only two pyrene-labeling schemes that can be dealt with in a straightforward
      manner, a Model Free (MF) analysis was applied to the global analysis of the
      fluorescence decays. Within experimental error, the I(E)/I(M) ratios and <k>
      obtained from, respectively, the steady-state fluorescence spectra and the time
      resolved fluorescence decays were found to increase linearly with increasing
      generation number. This result is inconsistent with the fact that both the
      I(E)/I(M) ratio and <k> are proportional to the local concentration of pyrene
      inside the dendrimer ([Py](loc)) which is not expected to increase with
      generation number if the excited pyrene is assumed to diffuse freely throughout
      the dendrimer interior. Since the core-dense model predicts that the dendrimer
      terminal ends can occupy any position throughout the dendrimer interior, these
      results suggest that excimer formation between the pyrene-labeled ends is
      enhanced due to the branched nature of the dendrimer.

PMID- 20701363
TI  - Kinetic transition network based on trajectory mapping.
AB  - The understanding of biomolecular systems can be greatly improved by constructing
      conformational transition networks. Network representation honestly reflects the
      intrinsic complexity of high-dimensional systems, which facilitates the
      estimation of various thermodynamic and kinetic properties. In this paper, we
      introduce the trajectory mapping (TM) method for naturally detecting the
      metastable states of biomolecules and for subsequently constructing the
      hierarchical kinetic transition networks. In TM, multiple simulation trajectories
      are mapped to high-dimensional vectors, and the interrelation between these
      trajectory-mapped vectors is analyzed to locate metastable states. Kinetic
      information can be quantitatively extracted through simple algebraic
      manipulations of the identified metastable states. We apply the TM method to a
      toy model and alanine dodeca-peptide. The polypeptide system is analyzed at two
      time scales, and the metastable states and interstate transition kinetics are
      correctly revealed.

PMID- 20701364
TI  - Structure and dynamics of a thermoresponsive microgel around its volume phase
      transition temperature.
AB  - Sustained drug delivery requires the use of multifunctional devices with enhanced
      properties. These properties include responsiveness to external stimuli (such as
      temperature, pH, ionic strength), ability to deliver suitably designed ligands to
      specific receptors, enhanced bioadhesion to cells, and cytocompatibility.
      Microgels represent one of such multifunctional drug delivery devices. Recently,
      we described the fabrication of a stable colloidal aqueous suspension of
      cytocompatible microgel spheres based on a poly(vinyl alcohol)/poly(methacrylate
      co-N-isopropylacrylamide) network ( Ghugare, S. Mozetic, P. Paradossi, G.
      Biomacromolecules 2009 , 10 , 1589 ). These microgel spheres undergo an entropy
      driven volume phase transition around the physiological temperature, this phase
      transition being driven by the incorporation of NiPAAm residues in the network.
      In that study, the microgel was loaded with the anticancer drug doxorubicin. As
      the microgel shrank, a marked increase in the amount of doxorubicin released was
      noted. Indeed, dynamic light scattering measurements showed the diameter
      reduction to be about 50%. In the present paper, we focus on some fundamental
      issues regarding modifications of the hydrogel architecture at a nanoscopic level
      as well as of the diffusive behavior of water associated with the polymer network
      around the volume phase transition temperature (VPTT). Sieving and size exclusion
      effects were studied by laser scanning confocal microscopy with the microgel
      exposed to fluorescent probes with different molecular weights. Confocal
      microscopy observations at room temperature and at 40 degrees C (i.e., below and
      above the VPTT) provided an evaluation of the variation of the average pore size
      (from 5 nm to less than 3 nm). Using quasielastic neutron scattering (QENS) with
      the IRIS spectrometer at ISIS, UK, the diffusive behavior of water molecules
      closely associated to the polymer network around the VPTT was investigated. A
      clear change in the values of diffusion coefficient of bound water was observed
      at the transition temperature. In addition, the local dynamics of the polymer
      itself was probed using the QENS spectrometer SPHERES at FRM II, Germany. For
      this study, the microgel was swollen in D(2)O. An average characteristic distance
      of about 5 A for the localized chain motions was evaluated from the elastic
      incoherent structure factor (EISF) and from the Q-dependence of the Lorentzian
      width.

PMID- 20701365
TI  - Electrical memory characteristics of a nondoped pi-conjugated polymer bearing
      carbazole moieties.
AB  - Poly[bis(9H-carbazole-9-ethyl)dipropargylmalonate] (PCzDPM) is a novel pi
      conjugated polymer bearing carbazole moieties that has been synthesized by
      polymerization of bis(9H-carbazole-9-ethyl)dipropargylmalonate with the aid of
      molybdenum chloride solution as the catalyst. This polymer is thermally stable up
      to 255 degrees C under a nitrogen atmosphere and 230 degrees C in air ambient;
      its glass-transition temperature is 147 or 128 degrees C, depending on the
      polymer chain conformation (helical or planar structure). The charge-transport
      characteristics of PCzDPM in nanometer-scaled thin films were studied as a
      function of temperature and film thickness. PCzDPM films with a thickness of 15
      30 nm were found to exhibit very stable dynamic random access memory (DRAM)
      characteristics without polarity. Furthermore, the polymer films retain DRAM
      characteristics up to 180 degrees C. The ON-state current is dominated by Ohmic
      conduction, and the OFF-state current appears to undergo a transition from Ohmic
      to space-charge-limited conduction with a shallow-trap distribution. The ON/OFF
      switching of the devices is mainly governed by filament formation. The filament
      formation mechanism for the switching process is supported by the metallic
      properties of the PCzDPM film, which result in the temperature dependence of the
      ON-state current. In addition, the structure of this pi-conjugated polymer was
      found to vary with its thermal history; this change in structure can affect
      filament formation in the polymer film.

PMID- 20701366
TI  - X-ray diffraction, FT-IR, and (13)C CP/MAS NMR structural studies of solvated and
      desolvated C-methylcalix[4]resorcinarene.
AB  - Solid C-methylcalix[4]resorcinarene solvated by acetonitrile and water (CAL-Me)
      and then modified by slow solvent evaporation (CAL-Me*) was studied using single
      crystal and powder X-ray diffraction, FT-IR, and (13)C CP/MAS NMR. The CAL-Me
      solvate crystallizes in the monoclinic P2(1)/n space group with three CH(3)CN and
      two H(2)O molecules in the asymmetric part of the unit cell. The CAL-Me molecules
      adopt a typical crown conformation with all of the hydroxyl groups of the aryl
      rings oriented up and all of the methyl groups disposed down (the rccc isomeric
      form). The crystalline network is formed by resorcinarene, CH(3)CN, and H(2)O
      molecules and assembled by intermolecular hydrogen bonds and weak C-H...A or C
      H...pi interactions. The desolvated CAL-Me* loses its crystalline character and
      becomes partly amorphous. It is devoid of CH(3)CN and deficient in water.
      However, the resorcinarene molecules still remain in the crown conformation
      supported by intramolecular hydrogen bonds, while intermolecular hydrogen bonds
      are considerably disintegrated. The work directs general attention to the problem
      of stability and polymorphism of resorcinarene solvates. It shows that the joint
      use of diffractometric and spectroscopic methods is advantageous in the
      structural studies of complex crystalline macromolecular systems. On the other
      hand, the solid-state IR and NMR spectroscopic analyses applied in tandem have
      been found highly beneficial to elucidate the disordered structure of poorly
      crystalline, desolvated resorcinarene.

PMID- 20701367
TI  - Reversible heat-set organogel based on supramolecular interactions of beta
      cyclodextrin in N,N-dimethylformamide.
AB  - This paper describes the first reversible, heat-set organogel based on the
      supramolecular interactions of beta-cyclodextrin (beta-CD). The gel was prepared
      by interaction of diphenylamine (DPA) with beta-CD and lithium chloride in N,N
      dimethylformamide (DMF). In this gel system, DPA could be gelated in DMF as the
      temperature increased and then dissolved again as the temperature decreased. In
      the microscopic structure of gel, beta-CDs play a key role in the formation of
      nanorods and microfibers. Some important features of the gel were observed. (1)
      The system is a multicomponent solution, in which each of the four components is
      required for the organogelation property. (2) The system is a reversible, thermo
      responsive organogel composed of small organic molecules. When the temperature is
      lower than T(gel), the gel transforms back into a solution. The reversible thermo
      transition was confirmed by differential scanning calorimetry (DSC). The gel
      system is responsive to the concentration of LiCl. No gel was formed without
      LiCl. The stimuli responses of the system with other salts such as KCl and NaCl
      were weaker than with LiCl. (4) The system is responsive to the addition of guest
      molecules. The structures and sizes of the guest molecules could influence the
      gel formation. Generally, T(gel) decreased by adding guest molecules in the gel
      system, but some guest molecules, whose structures are exactly fitted to the
      cavity of CDs, could prevent gel formation. This work may provide new avenues in
      delivery of functional molecules as well as design of intelligent materials and
      biomaterials.

PMID- 20701369
TI  - Conditions for equilibrium solid-stabilized emulsions.
AB  - Particular types of solid-stabilized emulsions can be thermodynamically stable as
      evidenced by their spontaneous formation and monodisperse droplet size, which
      only depends on system parameters. Here, we investigate the generality of these
      equilibrium solid-stabilized emulsions with respect to the basic constituents:
      aqueous phase with ions, oil, and stabilizing particles. From systematic
      variations of these constituents, we identify general conditions for the
      spontaneous formation of monodisperse solid-stabilized emulsions droplets. We
      conclude that emulsion stability is achieved by a combination of solid particles
      as well as amphiphilic ions adsorbed at the droplet surface, and low interfacial
      tensions of the bare oil-water interface of order 10 mN/m or below. Furthermore,
      preferential wetting of the colloidal particles by the oil phase is necessary for
      thermodynamic stability. We demonstrate the sufficiency of these basic
      requirements by extending the observed thermodynamic stability to emulsions of
      different compositions. Our findings point to a new class of colloid-stabilized
      meso-emulsions with a potentially high impact on industrial emulsification
      processes due to the associated large energy savings.

PMID- 20701368
TI  - Characterization of reaction intermediate aggregates in aniline oxidative
      polymerization at low proton concentration.
AB  - Aggregates of reaction intermediates form during the early stages of aniline
      oxidative polymerization whenever the initial mole ratio of proton concentration
      to aniline monomer concentration is low ([H(+)](0)/[An](0) <or= 1.0). Detailed
      characterization is carried out on those aggregates. The intermediate aggregates
      show a UV-Vis absorption peak at around 410 nm when dispersed in aqueous
      solution, whereas the peak is centered on 370 nm when dissolved in an organic
      solvent such as N-methylpyrrolidone. The electronic band gap decreases when the
      intermediates aggregate to form a solid, and thus, the absorption peak is red
      shifted. Gel permeation chromatography (GPC) shows the aggregates contain a major
      low molecular weight peak with a long tail. The oligoanilines with low molecular
      weights consistently show a UV-Vis absorption peak at around 370 nm. Mass
      spectrometry confirms that the intermediate aggregates contain mainly a component
      with mass number 363 (M + H(+)), likely a tetramer. UV-Vis, GPC, mass
      spectrometry, NMR, FTIR, and XRD characterization results are presented and
      chemical structures for the tetramer are proposed. The major components of the
      intermediate aggregates are likely highly symmetric phenazine- and
      dihydrophenazine-containing structures. These particular organic compounds have
      not been identified before as intermediates. The aggregation and precipitation of
      the tetramers apparently stabilizes these intermediates. The aggregates are
      highly crystalline, as evidenced by powder X-ray diffraction. A new reaction
      mechanism for the formation of these intermediates is proposed.

PMID- 20701370
TI  - Noncovalent polymerization and assembly in water promoted by thermodynamic
      incompatibility.
AB  - This work studies the phase separations between polymers and a small molecule in
      a common aqueous solution that do not have well-defined hydrophobic-hydrophilic
      separation. In addition to poly(acrylamide) (PAAm) and poly(vinyl alcohol) (PVA),
      poly(vinyl pyrrolidone) (PVP) also promotes liquid crystal (LC) droplet formation
      by disodium cromoglycate (5'DSCG) solvated in water. In the presence of these
      polymers, the concentration of 5'DSCG needed for forming LC droplets is
      substantially lower than that needed for forming an LC phase by 5'DSCG alone. To
      define the concentration ranges that 5'DSCG molecules form liquid crystals
      (either as droplets or as an isotropic-LC mixture), we constructed ternary phase
      diagrams for 5'DSCG, water, and a polymer - PVA, PVP, or PAAm. We discovered that
      PAAm with high molecular weight promotes LC droplet formation by 5'DSCG more
      effectively than PAAm with low molecular weight. At the same weight percentage,
      long-chain PAAm can cause 5'DSCG to form LC droplets in water, whereas short
      chain PAAm does not. Poly(vinyl pyrrolidone) (PVP), which has functional groups
      that are more dissimilar to 5'DSCG than PVA and PAAm, promotes LC droplet
      formation by 5'DSCG more effectively than either of the other two polymers.
      Additionally, small angle neutron scattering data revealed that the assembly
      structure of 5'DSCG promoted by the presence of PVA is similar to the thread
      structure formed by 5'DSCG alone. Together, these results reveal how noncovalent
      polymerization can be promoted by mixing thermodynamically incompatible molecules
      and elucidate the basic knowledge of nonamphiphilic colloidal science.

PMID- 20701371
TI  - Preparation of a stable graphene dispersion with high concentration by
      ultrasound.
AB  - With unique structure and extraordinary electronic, thermal, and mechanical
      properties, graphene fascinates the scientific community. Due to its hydrophobic
      feature, preparation of a stable and highly concentrated graphene dispersion
      without the assistance of dispersing agents has generally been considered a
      challenge. Chemical reduction of graphene oxide (GO) is one of the most important
      methods for preparing a graphene dispersion. The aggregation of graphene sheets
      is a key reason to destabilize the resulting dispersion during conversion of
      aqueous GO dispersion to graphene. In this study, by replacing mechanical
      stirring with ultrasonic irradiation, the aggregation of various intermediates is
      effectively suppressed during the process of reduction of GO. Hence, a stable
      graphene dispersion with a high concentration of 1 mg.mL(-1) and relatively pure
      graphene sheets are achieved, and the as-prepared graphene paper exhibits a high
      electric conductivity of 712 S.m(-1). Ultraviolet-visible absorption spectroscopy
      and X-ray photoelectron spectroscopy show that ultrasound is the essence of
      enhancing chemical reaction rate. Fourier transformed infrared spectra and Raman
      spectra indicate that ultrasound has less damage to the chemical and crystal
      structures of graphene.

PMID- 20701372
TI  - Star-shaped donor-pi-acceptor conjugated oligomers with 1,3,5-triazine cores:
      convergent synthesis and multifunctional properties.
AB  - Monodispersed oligomers have been widely developed and used in different
      optoelectronic areas due to their well-defined molecular structures, high purity,
      and solution processability. Star-shaped oligomers are especially interesting for
      OLED application because of their antiaggregation abilities and stable
      electroluminescence. In addition, star-shaped donor-pi-acceptor conjugated
      molecules are known to afford good nonlinear optical and two-photon absorption
      properties due to the intramolecular charge transfer and cooperative enhancement
      effects. In this context, three generations of highly soluble 1,3,5-triazine
      based donor-pi-acceptor compounds, TFT1, TFT2, and TFT3, were prepared through a
      convergent synthetic strategy and their optoelectronic properties were fully
      studied, which showed distinct correlations with the structures. Closed-aperture
      and open-aperture Z-scan methods were employed to measure the nonlinear
      refractive index and two-photon absorption properties of the oligomers,
      respectively. TFT1 showed a high nonlinear refractive index of 4.14 x 10(-12) esu
      in THF solution with an excitation wavelength of 800 nm. Also, TFT1 exhibited a
      large two-photon absorption cross section of 234 GM and a frequency up-converted
      two-photon excited fluorescence with a lambda(TPEF)(max) value of 527 nm under
      800 nm laser irradiation with a pulse duration of 140 fs. OLED devices using the
      spin-coated films of these oligomers as an active layer showed intensive blue
      electroluminescence with a maximum luminance of 3093 cd/m(2) at a current
      efficiency of 1.47 cd/A from TFT1.

PMID- 20701373
TI  - Ionic self-assembled wormlike nanowires and their cyclodextrin inclusion-tuned
      transition.
AB  - Wormlike nanowires have been successfully prepared via the ionic self-assembly
      (ISA) route from the cationic (ferrocenylmethyl)trimethylammonium iodide (FcMI)
      and the anionic sodium bis(2-ethyl-1-hexyl)sulfosuccinate (AOT). The formed FcM
      AOT complexes have been proved to possess a composition of equal molar ratio and
      show good redox activity also due to the introduction of organic metal ferrocene.
      These complexes exhibit an ordered hexagonal columnar structure with the lattice
      spacing D of 2.49 nm. More interestingly, the wormlike nanowires interweave
      themselves together to form a net-like structure, and some of them are large
      enough to exhibit a high-order crystal structure. In addition, such an ISA
      organized aggregate can be changed into vesicles by including the Fc blocks into
      beta-cyclodextrins to form another supramolecular complex. The supramolecular
      structure and morphology of the vesicles were characterized by transmission
      electron microscopy (TEM) and dynamic light scattering (DLS), respectively. Both
      the complex fabrication and transition mechanisms are discussed and found to be
      controlled by the inclusion equilibrium and the cooperative binding of
      noncovalent interactions, including the electrostatic interactions, pi-pi
      stacking, and amphiphilic hydrophobic association.

PMID- 20701374
TI  - Conformational changes at mesophase transitions in a ferroelectric liquid crystal
      by comparative DFT computational and (13)C NMR study.
AB  - In this work, we report a detailed investigation on both the conformational and
      the orientational ordering properties of a ferroelectric liquid crystal mesogen,
      namely, M10/**, through the combination of high resolution solid state (13)C NMR
      and density functional theory (DFT) computational methods. The trends of the
      observed (13)C chemical shift in the blue, cholesteric, and ferroelectric SmC*
      phases of M10/** were analyzed in terms of conformational changes occurring in
      the flexible parts of the molecule. In particular, we focused on the aliphatic
      alpha methylenoxy carbons because of their high sensitivity to mesophase
      environment, as evidenced by experimental (13)C chemical shift anisotropy (CSA).
      DFT computation of the chemical shift tensors as a function of geometrical
      parameters, such as dihedral angles, put in evidence significant changes in the
      average conformation at the mesophase transitions. The conformations predicted by
      DFT have been validated by comparing the calculated (13)C chemical shifts with
      those experimentally observed for the alkoxylic carbons, whose relative
      orientation plays a key role in establishing the overall conformation of the
      molecule in each liquid crystalline phase. Furthermore, the orientational order
      parameters of the relevant flexible fragments were calculated and found to be in
      good agreement with those characterizing similar systems, thus validating our
      approach.

PMID- 20701375
TI  - Interplay of ion-specific and charge-density effects in aqueous solutions of
      weakly charged ionenes as revealed by electric-transport measurements.
AB  - In 3,3-ionenes, one quaternary nitrogen is bonded to a chain of three methylene
      groups on each side, and in 6,9-ionene, it is bonded to a chain of six on one
      side and nine on the other. We examined how the solution properties of several
      ionenes changed with increased hydrophobicity of the polyion, depending on the
      nature of the counterion. We determined the electrical conductivities of aqueous
      solutions of 3,3-, 4,5-, 6,6-, and 6,9-ionene fluorides and bromides in the range
      of concentrations from 5 x 10(-3) to 1 x 10(-1) M and for the temperature
      interval 5-35 degrees C. Over these ranges, the conductivities of the ionenes
      were found to decrease with increasing concentration and increase with increasing
      temperature. The conductivity of 3,3-ionene bromide was lower than that of its
      fluoride analogue throughout the whole range of concentrations, whereas for the
      6,9-ionenes, the trend was reversed. For 4,5- and 6,6-ionene, we observed a
      crossover in the concentration dependence of conductivity. The conductivity data
      were compared with the predictions of Manning's theory and scaling theory.
      Separately determined transport-number values were combined with the conductivity
      data to obtain the fractions of so-called "free" counterions, f. For bromide
      samples, f increased from 3,3- to 6,9-ionene. In the case of fluoride
      counterions, the fraction of free counterions was the lowest for 3,3-ionene and,
      within the experimental uncertainty, approximately constant for the other less
      charged ionenes.

PMID- 20701376
TI  - Studies on interaction of poly(sodium acrylate) and poly(sodium styrenesulfonate)
      with cationic surfactants: effects of polyelectrolyte molar mass, chain
      flexibility, and surfactant architecture.
AB  - Isothermal titration microcalorimetry, turbidity, and steady-state fluorescence
      measurements have been used to study interactions of cationic ammonium gemini
      surfactant (C(12)C(6)C(12)Br(2)) and single-chain surfactant
      dodecyltrimethylammonium bromide (DTAB) with anionic polyelectrolytes poly(sodium
      styrenesulfonates) (NaPSS) and poly(sodium acrylates) (NaPAA) with different
      molar masses. Without any surfactants, NaPSS with lower molar mass has already
      self-aggregated into aggregates, whereas NaPAA has no aggregation at any molar
      mass. All of the polyelectrolytes show a remarkable interaction with the cationic
      surfactants. Compared with DTAB, C(12)C(6)C(12)Br(2) can bind to NaPSS and NaPAA
      at a very low concentration and has stronger interactions with NaPSS and NaPAA.
      The flexible NaPAA shows moderately endothermic enthalpies while interacting with
      the surfactants, but the interaction of the stiff NaPSS with the surfactants
      exhibits highly exothermic enthalpies. Moreover, the interaction of the stiff
      NaPSS with the surfactants strongly depends on the polyelectrolyte molar mass,
      but the polyelectrolyte molar mass almost does not affect the interaction of the
      flexible NaPAA with the surfactants. Especially, the effect of the
      polyelectrolyte molar mass becomes more significant when the polyelectrolytes
      interact with gemini surfactant than with single-chain surfactant. It is revealed
      that the effects of polyelectrolyte molar mass, chain flexibility, and surfactant
      architecture on surfactant/polyelectrolyte interactions confine each other.

PMID- 20701377
TI  - The mechanism of metal cation binding in two nalidixate calixarene conjugates. A
      langmuir film and molecular modeling study.
AB  - The two new p-tert-butylcalix[4]arene derivatives described here bear one or two
      nalidixic acid arms linked to the lower calixarene rim via the quinolone
      carboxylate moiety. These derivatives were synthesized in order to investigate
      two important features of molecules conceived as potential antibiotics, namely,
      metal cation complexation and interfacial properties, and the way in which they
      interrelate. The properties of the calixarene derivatives were studied in
      monomolecular films spread on pure water and on aqueous subphases containing
      biologically relevant mono- and divalent metal cations. These systems were
      examined via surface pressure and surface electrical potential measurements,
      polarization modulation infrared reflection absorption spectroscopy, and
      molecular modeling. Molecular modeling shows that important differences exist,
      first, between the structure and stability of the complexes formed with the two
      derivatives and, second, between their mono- and dication complexes. Correlating
      the properties of the monolayers with those of the modeled molecules lets us
      propose that the derivatives bearing one or two nalidixic pending arms form
      preferentially inter- and intramolecular complexes, respectively. The results
      obtained in this study indicate that a possible biological role of the nalidixic
      arms grafted on the calixarene crown may be revealed upon cation complexation.

PMID- 20701378
TI  - Comparative electrochemical behaviors of a series of SH-terminated-functionalized
      porphyrins assembled on a gold electrode by scanning electrochemical microscopy
      (SECM).
AB  - The synthetic sulfhydryl porphyrin compounds (abbreviated as H(2)TPPO(CH)(n)SH, n
      = 3, 4, 6, 9, 10, 12), with a systematic series of spacers containing large end
      groups-porphyrin rings and different length alkyl chains, were prepared to
      investigate the electron transport (ET) kinetics between a gold electrode
      modified with H(2)TPPO(CH)(n)SH and a redox mediator (ferricyanide). The three ET
      kinetics were clearly distinguishable by scanning electrochemical microscopy
      (SECM). As shown by the rate constants (k(ox)) of bimolecular ET between
      H(2)TPPO(CH)(n)SH and the redox mediator, the rate constants (k(b)) of tunneling
      ET between the underlying gold electrode and the redox mediator, and the rate
      constants (k') of pinhole or defects, ET depended upon alkyl chain length,
      surface coverage, and the concentration of the redox mediator. Among all of them,
      the bimolecular reaction which contained electron donor (mediators) and electron
      acceptor (SAMs) was a dynamic cyclic process. That strongly suggested that the
      bimolecular reaction should mimic ET of photosystem II in chloroplast.

PMID- 20701379
TI  - Reverse micelle induced flipping of binding site and efficiency of albumin
      protein with an ionic styryl dye.
AB  - The effect of reverse micelle environment on the binding mechanism of 2-(4
      (dimethylamino)styryl)-1-methylpyridinium iodide (DASPMI) with Bovine Serum
      Albumin (BSA) compared with that in buffer solution has been investigated in this
      paper with the help of steady state and time-resolved emission spectroscopy along
      with molecular docking to have a correct picture about binding. The binding of
      DASPMI with attachment efficiency of 30% and 70% at site I (subdomain IIA) and
      site II (subdomain IIIA) of BSA, respectively, in buffer solution gets reversed
      inside a reverse micelle. The bigger cavity size of site II in buffer solution
      ushers the dye with increased attachment efficiency and in reverse micelle change
      in pi-stacking and hydrophobic interaction control the attachment efficiency. The
      calculated Forster distance gets curtailed as the environment changes from buffer
      to reverse micelle. The binding becomes stronger with a smaller gap between the
      probe and Trp-214 inside the reverse micelle than that in buffer solution.

PMID- 20701380
TI  - Sulfonated poly(arylene ether sulfone ketone) multiblock copolymers with highly
      sulfonated block. Fuel cell performance.
AB  - Poly(arylene ether sulfone ketone) (SPESK) multiblock copolymers having highly
      sulfonated hydrophilic blocks were synthesized and the fuel cell performance with
      the copolymers was investigated. A membrane electrode assembly (MEA) using an
      SPESK ionomer with an ion exchange capacity of 1.8 mequiv g(-1) as membrane and
      Nafion as the electrode binder showed comparable fuel cell performance and ohmic
      resistance to that using a Nafion NRE 211 membrane at 80 degrees C and 30%
      relative humidity (RH). A Nafion-free, all-SPESK MEA using SPESK as both the
      membrane and the binder was operable at 100 degrees C and 50% RH. The fuel cell
      performance was limited not only by the proton conductivity of the SPESK membrane
      but also by the low water flux through the membrane and specific adsorption of
      the ionomer on the platinum catalyst.

PMID- 20701381
TI  - Interactions of ionic liquids and water.
AB  - Experimental excess enthalpies of ionic liquid and water mixtures in combination
      with calculated CHELPG atomic charges were used to investigate the interactions
      between the species in solution. The excess enthalpies of ionic liquids in water
      were obtained by calorimetry, using a Setaram C80 calorimeter, including
      temperatures from (313.15 to 348.15) K and the entire range of composition. The
      ionic liquids investigated all contain the 1-ethyl-3-methylimidazolium cation
      except one, which has an added hydroxyl group on the cation (1-(2-hydroxyethyl)-3
      methylimidazolium cation). The anions investigated are ethylsulfate,
      methylsulfate, hydrogensulfate, trifluoromethanesulfonate, methanesulfonate, and
      trifluoroacetate, and these will demonstrate the effect of systematically varying
      the substituents on the anion. The CHELPG atomic charges on the cations and
      anions were calculated using the Gaussian 03 program. The CHELPG atomic charges
      are consistent with the observed trends in excess enthalpy and provide insight
      into cation/water, anion/water, and cation/anion interactions.

PMID- 20701382
TI  - Efficient sampling of atomic configurational spaces.
AB  - We describe a method to explore the configurational phase space of chemical
      systems. It is based on the nested sampling algorithm recently proposed by
      Skilling (AIP Conf. Proc. 2004, 395; J. Bayesian Anal. 2006, 1, 833) and allows
      us to explore the entire potential energy surface (PES) efficiently in an
      unbiased way. The algorithm has two parameters which directly control the trade
      off between the resolution with which the space is explored and the computational
      cost. We demonstrate the use of nested sampling on Lennard-Jones (LJ) clusters.
      Nested sampling provides a straightforward approximation for the partition
      function; thus, evaluating expectation values of arbitrary smooth operators at
      arbitrary temperatures becomes a simple postprocessing step. Access to absolute
      free energies allows us to determine the temperature-density phase diagram for LJ
      cluster stability. Even for relatively small clusters, the efficiency gain over
      parallel tempering in calculating the heat capacity is an order of magnitude or
      more. Furthermore, by analyzing the topology of the resulting samples, we are
      able to visualize the PES in a new and illuminating way. We identify a discretely
      valued order parameter with basins and suprabasins of the PES, allowing a
      straightforward and unambiguous definition of macroscopic states of an atomistic
      system and the evaluation of the associated free energies.

PMID- 20701383
TI  - A new coarse-grained model for water: the importance of electrostatic
      interactions.
AB  - A new coarse-grained (CG) model is developed for water. Each CG unit consists of
      three charged sites, and there is an additional nonelectrostatic soft interaction
      between central sites on different units. The interactions are chosen to mimic
      the properties of 4-water clusters in atomistic simulations: the nonelectrostatic
      component is modeled using a modified Born-Mayer-Huggins potential, and the
      charges are chosen to reproduce the dipole moment and quadrupole moment tensor of
      4-water clusters from atomistic simulations. The parameters are optimized to
      reproduce experimental data for the compressibility, density, and permittivity of
      bulk water and the surface tension and interface potential for the air-water
      interface. This big multipole water (BMW) model represents a qualitative
      improvement over existing CG water models; for example, it reproduces the dipole
      potential in membrane-water interface when compared to experiment, with modest
      additional computational cost as compared to the popular MARTINI CG model.

PMID- 20701384
TI  - Enhancement of the chemiluminescence of two isoluminol derivatives by
      nanoencapsulation with natural cyclodextrins.
AB  - The chemiluminescence (CL) yield of two isoluminol derivatives, N-(4-aminobutyl)
      N-ethylisoluminol (ABEI) and N-(6-aminohexyl)-N-ethylisoluminol (AHEI), is
      remarkably increased in the presence of natural cyclodextrins (CDs). The most
      notable effect is produced by the addition of gamma-CD that produces enhancements
      up to 15-fold in the light emission of both compounds. Although proton nuclear
      magnetic resonance ((1)H NMR) measurements prove the encapsulation of these
      luminescent reagents in the CDs, with more stable associations by decreasing the
      width of the CD cavity, the improvement in the light emission of ABEI and AHEI is
      mainly due to the topology of the complexes. Evaluation of the rotating frame
      Overhauser effect spectroscopy (ROESY) spectra cross-peaks combined with
      semirigid-docking simulations has been used to gather information about the
      spatial conformation of the guest molecules into the CDs. These calculations have
      shown that a deeper inclusion in the CD cavity of the heterocyclic moiety of the
      luminescent molecules is directly related with a higher enhancement in the CL.
      The augment of the CL by natural CDs is of interest for increasing the detection
      limit in biochemical assays or liquid chromatography, for example, in which the
      CL of these compounds serves to quantify other molecular species that may take
      part, direct or indirectly, in the luminescent reaction.

PMID- 20701385
TI  - Structure of spherical electric double layers containing mixed electrolytes: a
      systematic study by Monte Carlo simulations and density functional theory.
AB  - The structure of spherical electric double layers in the presence of mixed
      electrolytes is studied using Monte Carlo simulation and density functional
      theory within the restricted primitive model. The macroion is modeled as an
      impenetrable charged hard sphere carrying a uniform surface charge density,
      surrounded by the small ions represented as charged hard spheres, and the solvent
      is taken as a dielectric continuum. The density functional theory uses a
      partially perturbative scheme, where the hard-sphere contribution to the one
      particle correlation function is evaluated using weighted density approximation
      and the ionic interactions are calculated using a second-order functional Taylor
      expansion with respect to a bulk electrolyte. The Monte Carlo simulations have
      been performed in canonical ensemble. The system is studied at varying ionic
      concentrations, at different concentration ratios of mono- and multivalent
      counterions of mixed electrolytes, at different diameters of hard spheres, at
      different macroion radius, and at varying polyion surface charge densities. The
      theoretical predictions in terms of the density profiles and the mean
      electrostatic potential profiles are found to be in good agreement with the
      simulation results. This model study shows clear manipulations of ionic size and
      charge correlations in dictating a number of interesting phenomena relating to
      width of the diffuse layer and charge inversion under different parametric
      conditions.

PMID- 20701386
TI  - On the use of excess entropy scaling to describe the dynamic properties of water.
AB  - We use molecular dynamics and transition-matrix Monte Carlo simulation to study
      the ability of entropy scaling relationships to describe kinetic properties of
      the extended simple point charge water model. We examine translational and
      rotational diffusivities, a characteristic relaxation time for rotational motion,
      and a collective relaxation time stemming from analysis of the coherent
      intermediate scattering function. We consider both the thermodynamic excess
      entropy and the contribution to the two-body excess entropy related to center-of
      mass correlations as scaling variables. Calculations are performed over a broad
      range of conditions that span from the dense supercooled liquid regime to the
      critical region. We find that the thermodynamic excess entropy serves as a
      suitable metric for describing reduced transport properties for state conditions
      corresponding to temperatures above the onset of water's structurally anomalous
      region, defined by states points for which the excess entropy increases upon
      compression at constant temperature. In contrast, the aforementioned two-body
      contribution to the excess entropy cannot be used to quantitatively predict
      kinetic properties over the wide range of conditions explored here. For state
      points above the onset temperature of the structurally anomalous region, reduced
      transport property data collapse onto common curves when expressed as a function
      of the thermodynamic excess entropy. Below this temperature, data fall onto
      isochore-specific curves. Our results show a relatively strong correlation
      between the translational diffusivity and excess entropy and a noticeably weaker
      correlation between rotational mobility and excess entropy.

PMID- 20701387
TI  - Comparison of the effects of possible mechanical stimuli on the rate of
      biochemical reactions.
AB  - The aim of this work is to address the question of what constitutes a mechanical
      stimulation of biochemical reactions in general and further to compare the
      importance of the two possible mechanical stimulations: shear rate and the rate
      of volume variation. Using linear nonequilibrium thermodynamics, the Curie
      principle (the relation for coupling phenomena) is retrieved for a
      phenomenological relation for a scalar flux in an isotropic system. From these
      phenomenological relations for the rate of chemical reaction, it is established
      that the only scalar quantity related to the rate of deformation tensor D that
      cannot be neglected is the rate of volume variation D((1)). This leads us to the
      conclusion that, although tissues are exposed to all variety of mechanical
      factors: straining, shear, pressure, and even dynamic electric fields, the volume
      variation rate D((1)) is the most important mechanical stimulus driving the
      processes in them.

PMID- 20701388
TI  - Structural dynamics of the box C/D RNA kink-turn and its complex with proteins:
      the role of the A-minor 0 interaction, long-residency water bridges, and
      structural ion-binding sites revealed by molecular simulations.
AB  - Kink-turns (K-turns) are recurrent elbow-like RNA motifs that participate in
      protein-assisted RNA folding and contribute to RNA dynamics. We carried out a set
      of molecular dynamics (MD) simulations using parm99 and parmbsc0 force fields to
      investigate structural dynamics of the box C/D RNA and its complexes with two
      proteins: native archaeal L7ae protein and human 15.5 kDa protein, originally
      bound to very similar structure of U4 snRNA. The box C/D RNA forms K-turn with A
      minor 0 tertiary interaction between its canonical (C) and noncanonical (NC)
      stems. The local K-turn architecture is thus different from the previously
      studied ribosomal K-turns 38 and 42 having A-minor I interaction. The simulations
      reveal visible structural dynamics of this tertiary interaction involving
      altogether six substates which substantially contribute to the elbow-like
      flexibility of the K-turn. The interaction can even temporarily shift to the A
      minor I type pattern; however, this is associated with distortion of the G/A base
      pair in the NC-stem of the K-turn. The simulations show reduction of the K-turn
      flexibility upon protein binding. The protein interacts with the apex of the K
      turn and with the NC-stem. The protein-RNA interface includes long-residency
      hydration sites. We have also found long-residency hydration sites and major ion
      binding sites associated with the K-turn itself. The overall topology of the K
      turn remains stable in all simulations. However, in simulations of free K-turn,
      we observed instability of the key C16(O2')-A7(N1) H-bond, which is a signature
      interaction of K-turns and which was visibly more stable in simulations of K
      turns possessing A-minor I interaction. It may reflect either some imbalance of
      the force field or it may be a correct indication of early stages of unfolding
      since this K-turn requires protein binding for its stabilization. Interestingly,
      the 16(O2')-7(N1) H- bond is usually not fully lost since it is replaced by a
      water bridge with a tightly bound water, which is adenine-specific similarly as
      the original interaction. The 16(O2')-7(N1) H-bond is stabilized by protein
      binding. The stabilizing effect is more visible with the human 15.5 kDa protein,
      which is attributed to valine to arginine substitution in the binding site. The
      behavior of the A-minor interaction is force-field-dependent because the parmbsc0
      force field attenuates the A-minor fluctuations compared to parm99 simulations.
      Behavior of other regions of the box C/D RNA is not sensitive to the force field
      choice. Simulation with net-neutralizing Na(+) and 0.2 M excess salt conditions
      appear in all aspects equivalent. The simulations show loss of a hairpin
      tetraloop, which is not part of the K-turn. This was attributed to force field
      limitations.

PMID- 20701390
TI  - Temperature dependence of hydrogen-bond dynamics in acetic acid-water solutions.
AB  - An inelastic UV scattering experiment has been carried out on acetic acid-water
      solutions as a function of temperature and concentration. The analysis of
      experimental data indicates the presence of a crossover temperature (T(c)
      approximately 325 +/- 10 K). Above T(c), the energy of hydrogen bonds responsible
      for water-acetic acid and acetic acid-acetic acid interactions is strongly
      reduced. This leads to a reduction in the average number of water molecule
      interacting with acetic acid, as well as to a lower number of acetic acid
      clusters. The latter behavior can be mainly ascribed to a temperature change in
      the activation energy of carboxylic groups of acetic acid. These results may be
      also relevant to better understand the folding mechanism in protein-water
      solutions.

PMID- 20701391
TI  - Predicting the acid/base behavior of proteins: a constant-pH Monte Carlo approach
      with generalized born solvent.
AB  - The acid/base properties of proteins are essential in biochemistry, and proton
      binding is a valuable reporter on electrostatic interactions. We propose a
      constant-pH Monte Carlo strategy to compute protonation free energies and
      pK(a)'s. The solvent is described implicitly, through a generalized Born model.
      The electronic polarizability and backbone motions of the protein are included
      through the protein dielectric constant. Side chain motions are described
      explicitly, by the Monte Carlo scheme. An efficient computational algorithm is
      described, which allows us to treat the fluctuating shape of the protein/solvent
      boundary in a way that is numerically exact (within the GB framework); this
      contrasts with several previous constant-pH approaches. For a test set of six
      proteins and 78 titratable groups, the model performs well, with an rms error of
      1.2 pH units. While this is slightly greater than a simple Null model (rms error
      of 1.1) and a fully empirical model (rms error of 0.9), it is obtained using
      physically meaningful model parameters, including a low protein dielectric of
      four. Importantly, similar performance is obtained for side chains with large and
      small pK(a) shifts (relative to a standard model compound). The titration curve
      slopes and the conformations sampled are reasonable. Several directions to
      improve the method further are discussed.

PMID- 20701392
TI  - Detection of molecular interactions with modified ferrocene self-assembled
      monolayers.
AB  - Ferrocene-terminated self-assembled monolayers (Fc-SAMs) are one of the most
      studied molecular aggregates on metal electrodes. They are easy to fabricate and
      provide a stable and reproducible system to investigate the effect of the
      microenvironment on the electron transfer parameters. We propose a novel
      application for Fc-SAMs, the detection of molecular interactions, based on the
      modification of the SAM with target-specific receptors. Mixed SAMs were
      fabricated by coimmobilization on Au electrodes of thiolated alkane chains with
      three different head groups: hydroxy terminating head group, ferrocene head
      group, and a functional head group such as biotin. Upon binding, the intrinsic
      electric charge of the target (e.g., streptavidin) modifies the electrostatic
      potential at the plane of electron transfer, causing a shift in the formal
      potential E degrees '. The SAMs were characterized by AC voltammetry. The
      detection mechanism is confirmed by measurements of formal potential as a
      function of electrolyte pH.

PMID- 20701389
TI  - Effect of molecular crowding and ionic strength on the isothermal hybridization
      of oligonucleotides.
AB  - The isothermal hybridization of complementary oligonucleotides, 15-mer, 25-mer,
      35-mer, and a molecular beacon, was investigated under varying conditions of
      molecular crowding and ionic strength, using hypochromicity to follow strand
      pairing and polyethylene glycol as a crowding agent. Thermodynamic analysis of
      the results revealed the addition of counterions to the oligonucleotide
      backbones, DeltaPsi, to be dependent on the strand GC content and the molecular
      crowding. A decrease in DeltaPsi was observed, with both increasing GC% and
      solution PEG content. In contrast, the number of bound water molecules depended
      on the activity of Na(+), where two regimes were observed. At a(Na(+)) < 0.05 and
      increasing molecular crowding, water molecules were released into the DNA
      solutions, and oligonucleotide pairing was favored with both increasing
      hydrophobic forces, whereas at a(Na(+)) >or= 0.05, water molecules were bound to
      the strands, and the extent of double strand formation decreased with increasing
      PEG wt %.

PMID- 20701394
TI  - Interaction kinetic and structural dynamic analysis of ligand binding to
      acetylcholine-binding protein.
AB  - The mechanism of agonist interactions with Cys-loop ligand-gated ion channels has
      been studied using the acetylcholine-binding protein (AChBP) from Lymnaea
      stagnalis as a model protein and acetylcholine, nicotine, epibatidine, and a
      series of substituted quinuclidines as ligands. A biosensor-based assay for
      direct interaction studies of immobilized AChBP and small molecule ligands was
      developed. It allowed the characterization of the interaction kinetics of the
      ligands and the structural dynamics of the protein. The interactions with AChBP
      were very sensitive to variations in the experimental conditions and showed
      several types of complexities. These could be resolved into two types of ligand
      induced secondary effects with different kinetics, representing fast and slow
      conformational changes. The data could be rationalized in a mechanistic model,
      and a structural interpretation of the interaction was obtained by molecular
      modeling involving induced fit and loop flexibility simulations. The data suggest
      that AChBP exhibits ligand-induced structural dynamics, as expected for the
      ligand gating mechanism of Cys-loop receptors. It shows that the formation of the
      initial encounter complex between AChBP and ligands is very rapid, in accordance
      with the functional characteristics required of neurotransmission. These
      developed procedures will enable further exploration of the mechanism of Cys-loop
      receptor function and the identification of specific ligands suitable for
      pharmacological use.

PMID- 20701395
TI  - Stereoisomerization of beta-hydroxy-alpha-sulfenyl-gamma-butyrolactones
      controlled by two concomitant 1,4-type nonbonded sulfur-oxygen interactions as
      analyzed by X-ray crystallography.
AB  - We have synthesized nine beta-hydroxy-alpha-sulfenyl-gamma-butyrolactones having
      different substituents. The syn-anti or syn-syn lactones (or any mixture of both)
      invariably isomerized into syn-anti/syn-syn lactones in a ratio of approximately
      6/4. The other two possible isomeric lactones (anti-syn or anti-anti) were never
      observed. The crystal structures of syn-syn lactones have been determined. We
      found sulfur-oxygen distances to be less than the sum of the van der Waals radii
      (3.3 A), with the angle formed among the hydroxylic oxygen, sulfur, and
      quaternary aromatic carbon being close to 180 degrees. In addition, carbonylic
      oxygen-sulfur is directed <40 degrees from the perpendicular to the C-S-C.
      Theoretical calculations were performed which emphasize the directionality of the
      sulfur-oxygen interaction. The X-ray and theoretical studies demonstrate that two
      concomitant, attractive 1,4 intramolecular interactions of divalent sulfur with
      both carbonyl and hydroxyl oxygens are the driving force for the aforementioned
      stereochemical preference. Then nonbonded sulfur-oxygen interactions would
      control the stereoselectivity of the reaction. The same features are observed in
      the X-ray structure of a beta-hydroxy-alpha-sulfinyl-gamma-butyrolactone.

PMID- 20701396
TI  - Electron transfer properties of alkoxyl radicals. A time-resolved kinetic study
      of the reactions of the tert-butoxyl, cumyloxyl, and benzyloxyl radicals with
      alkyl ferrocenes.
AB  - A time-resolved kinetic study on the reactions of the tert-butoxyl (t-BuO*),
      cumyloxyl (CumO*), and benzyloxyl (BnO*) radicals with alkylferrocenes has been
      carried out in MeCN solution. With all radicals, clear evidence for an electron
      transfer (ET) process has been obtained, and with the same ferrocene donor, the
      reactivity has been observed to increase in the order t-BuO* < CumO* < BnO*, with
      the difference in reactivity approaching 3 orders of magnitude on going from t
      BuO* to BnO*. With BnO*, an excellent fit to the Marcus equation has been
      obtained, from which a value of the reduction potential of BnO* (E
      degrees(BnO*/BnO(-)) = 0.54 V/SCE) has been derived. The latter value appears,
      however, to be significantly higher than the previously determined reduction
      potential values for alkoxyl radicals and in contrast with the differences in the
      computed solution-phase electron affinities determined for t-BuO*, CumO*, and
      BnO*, indicating that the reaction of BnO* with ferrocene donors may not be
      described in terms of a straightforward outer sphere ET mechanism. From these
      data, and taking into account the available value of the reduction potential for
      CumO*, a value of E degrees (BnO*/BnO(-)) = -0.10 V/SCE has been estimated. On
      the basis of computational evidence for the formation of a pi-stacked prereaction
      complex in the reaction between BnO* and DcMFc, an alternative ET mechanism is
      proposed for the reactions of both CumO* and BnO*. In these cases, the
      delocalized nature of the unpaired electron allows for the aromatic ring to act
      as an electron relay by mediating the ET from the ferrocene donor to the formal
      oxygen radical center. This hypothesis is also in line with the observation that
      both BnO* and CumO* react with the ferrocene donors with rate constants that are
      in all cases at least 2 orders of magnitude higher than those measured for t
      BuO*, wherein the radical is well-localized.

PMID- 20701397
TI  - On the light-driven isomerization of a model asymmetric molecular rotor:
      conformations and conical intersections of 2-cyclopentylidene-tetrahydrofuran.
AB  - The ground state potential energy surface of the model molecular rotor 2
      cyclopentylidene-tetrahydrofuran (CPTHF) has been characterized by calculating
      minimum energy conformations, racemization pathways, and rotational barriers with
      high level ab initio electronic structure calculations. Two conformers with their
      corresponding enantiomers are found. The activation barriers for racemization are
      negligible, therefore thermal racemization takes place at room temperature.
      Torsional transition states, calculated using multiconfigurational CASSCF
      calculations, show twisted and pyramidalized biradical structures. Additionally,
      the photochemistry of CPTHF has been investigated using the accurate MS
      CASPT2/CASSCF methodology. In the UV spectrum it is found that the spectroscopic
      state is the S(1), which corresponds to a pipi* transition within the ethylene
      moiety. To understand light-triggered isomerization around the C=C bond, five
      conical intersections between the S(0) and S(1) have been located for each
      conformer of CPTHF, which allow the system to rapidly decay to the electronic
      ground state.

PMID- 20701398
TI  - Secondary hydrogen isotope effects on the structure and stability of cation-pi
      complexes (cation = Li(+), Na(+), K(+) and pi = acetylene, ethylene, benzene).
AB  - Secondary hydrogen isotope effects on the geometries, electronic wave functions
      and binding energies of cation-pi complexes (cation = Li(+), Na(+), K(+) and pi =
      acetylene, ethylene, benzene) are investigated with NEO/HF and NEO/MP2 methods.
      These methods determine both electronic and nuclear wave functions
      simultaneously. Our results show that an increase of the hydrogen nuclear mass
      leads to the elongation of the cation-pi bond distance and the decrease in its
      binding energy. An explanation to this behavior is given in terms of the changes
      in the pi-molecule electronic structure and electrostatic potential induced by
      isotopic substitutions.

PMID- 20701399
TI  - A review of 25 years' experience with the NovoPen family of insulin pens in the
      management of diabetes mellitus.
AB  - NovoPen, the first insulin pen, was introduced in 1985. This review article is an
      update of a review paper published in 2006 on 20 years' use of the NovoPen family
      of insulin pens in the management of diabetes mellitus. The literature searches
      conducted in the earlier review article were updated with search results for new
      articles published since April 2005. This was followed by an iterative search of
      references cited in identified publications and by searches of abstracts from
      proceedings of major international diabetes conferences since 2005. Most of the
      original studies identified in the 2006 review showed that insulin regimens using
      the NovoPen family of insulin pens were at least as effective (and in some cases
      superior) in maintaining glycaemic control and were as safe (in terms of
      hypoglycaemia) as conventional insulin regimens employing vials and syringes.
      Most patients preferred the various NovoPen insulin pens over vials and syringes,
      with some evidence suggesting that the use of discreet devices, such as those of
      the NovoPen family, facilitates intensive insulin therapy regimens, thereby
      helping to improve lifestyle flexibility. The new search results showed that the
      current generation of the device for the adult population, NovoPen 4, retains
      these benefits and further meets patients' needs by improving ease of use,
      convenience and discretion, which may be particularly important for those with
      manual dexterity, visual or auditory impairments. There was also evidence that
      healthcare professionals would be more likely to recommend NovoPen 4 to their
      patients than other devices. The recently introduced NovoPen Echo, designed
      specifically for the paediatric population, combines half-increment dosing with a
      memory function that can be used to retrieve information about the time and
      amount of the last dose, potentially reducing the fear of double dosing or
      missing a dose. Evidence obtained from the new searches suggested that paediatric
      patients, their parents and healthcare professionals were highly satisfied with
      NovoPen Echo overall, with most paediatric patients rating it their favourite pen
      compared with other insulin pens. In conclusion, new data published over the last
      5 years on the use of NovoPen devices add to the large body of published evidence
      supporting the patient-related benefits of durable insulin injection pens in the
      treatment of diabetes since the first such pen was introduced in 1985. Together,
      the benefits of NovoPen are considered likely to improve both patients' quality
      of life and their compliance with therapy.

PMID- 20701400
TI  - Safety of lornoxicam in the treatment of postoperative pain: a post-marketing
      study of analgesic regimens containing lornoxicam compared with standard
      analgesic treatment in 3752 day-case surgery patients.
AB  - BACKGROUND: Post-marketing surveillance studies can provide supplemental data on
      the safety of medications in the general population. OBJECTIVE: This study aimed
      to evaluate the safety of analgesic regimens including the NSAID lornoxicam in
      the short-term treatment of postoperative pain in a clinically relevant
      population. STUDY DESIGN: Randomized, open-label, multicentre, multinational,
      observational cohort study of 4 days' duration. SETTING: In-hospital
      postoperative setting, with discharge to home treatment within 24 hours of
      surgery. PARTICIPANTS: Adults aged > or =18 years expected to be in need of
      analgesic treatment after day-case surgery. INTERVENTION: Analgesic regimens
      containing lornoxicam were compared with a standard analgesic treatment, which
      was defined as the treatment that the patient would normally receive at the
      centre. MAIN OUTCOME MEASURES: Following day-case surgery, patients were provided
      with appropriate analgesic medication, and adverse events (AEs; defined as all
      recorded events with symptoms) were recorded by the investigator during the in
      hospital stay and by the patient for the next 3 days using entries recorded
      morning and evening in a patient diary. Statistical analyses tested for between
      treatment differences in AEs, adverse drug reactions (ADRs; defined as events
      probably, possibly or unlikely to be related to treatment) and gastrointestinal
      AEs (GI-AEs). RESULTS: A total of 4152 patients were randomized to treatment.
      Since 400 patients did not take any analgesic, the safety population consisted of
      1838 patients for lornoxicam and 1914 patients for standard analgesic treatment.
      Demographic and disease characteristics were similar between the two treatment
      groups, as were the type of surgery and the anaesthesia used in surgery. In the
      safety population, 16.9% of patients received no analgesic in hospital, and when
      analgesics were provided they were often administered in combination. Similarly,
      approximately 17% of patients did not take any analgesics at home. AEs were
      reported in 27.1% and 29.4% of patients in the lornoxicam and standard analgesic
      treatment groups, respectively, and ADRs constituted the majority of these
      events. No significant differences were demonstrated with regard to the incidence
      of AEs between the two groups. Most events were of mild or moderate intensity.
      Consistent with what may be expected for an NSAID, most AEs with lornoxicam were
      related to the GI system. GI-AEs were reported in 19.5% and 21.3% of patients in
      the lornoxicam and standard analgesic treatment groups, respectively, and most of
      these were considered ADRs. Most patients were satisfied with their pain
      treatment both in hospital and at home. CONCLUSION: Lornoxicam-containing
      regimens are as well tolerated as other analgesic regimens over 4 days in the
      treatment of postoperative pain.

PMID- 20701401
TI  - Effect of cilnidipine on normal to marginally elevated urine albumin-creatinine
      ratio in asymptomatic non-diabetic hypertensive patients: an exponential decay
      curve analysis.
AB  - BACKGROUND: High-normal urinary albumin excretion has been reported to have
      clinical significance with respect to progression of proteinuria and
      hypertension. OBJECTIVE: We analysed the effect of cilnidipine (10 mg/day) on
      morning systolic blood pressure (SBP) and urine albumin-creatinine ratio (UACR)
      in 16 non-diabetic hypertensive patients with a normal to marginally elevated
      UACR (mean +/- SD 29.4 +/- 21.7; range 7.5-72.9 mg/g creatinine). METHODS:
      Sequential home BP and UACR data were fitted to a simple exponential function as
      follows: where y is SBP (mmHg) or UACR (mg/g creatinine); alpha is the extent of
      the SBP (mmHg)- or UACR (mg/g creatinine)-lowering effect; beta (days) is the
      time-constant for SBP or UACR decrease; t is the number of days after the start
      of cilnidipine administration; and gamma is the finally stabilized SBP (mmHg) or
      UACR (mg/g creatinine). RESULTS: Mean +/- SD morning SBP and UACR decreased by
      20.4 +/- 11.4 mmHg and 15.2 +/- 13.1 mg/g creatinine, respectively, as determined
      by coefficient alpha. The mean +/- SD time-constant for UACR decrease was
      significantly longer than that for BP decrease (43.5 +/- 22.9 vs 15.4 +/- 7.1
      days). UACR reduction correlated with pre-treatment UACR values (correlation
      coefficient [R] = 0.88, p < 0.01) but not with BP decrease. CONCLUSIONS: The
      present study demonstrated that cilnidipine reduced UACR in hypertensive patients
      with normal to marginally elevated UACR independent of its BP-lowering effect.

PMID- 20701402
TI  - Aripiprazole as an augmentation agent in treatment-resistant body dysmorphic
      disorder.
AB  - Body dysmorphic disorder (BDD) is a relatively common and severe disorder for
      which pharmacotherapy has been only minimally studied. BDD often appears to
      respond to selective serotonin reuptake inhibitors (SSRIs), but many patients do
      not respond or respond only partially. Investigation of SSRI augmentation
      strategies is therefore needed. We report a case of treatment-resistant BDD that
      was successfully treated with pharmacological augmentation of fluvoxamine with
      aripiprazole. The patient, a 43-year-old woman, had been taking a stable dose of
      fluvoxamine (400 mg/day) for 6 months when she was started on aripiprazole (10
      mg/day). After 10 weeks of this treatment, her clinical condition improved
      markedly, as indicated by a significant decrease in the Body Dysmorphic Disorder
      Examination score. This case presents some preliminary evidence that addition of
      the atypical antipsychotic agent aripiprazole may be useful in patients with
      treatment-resistant BDD. However, results from controlled studies are needed to
      support this finding.

PMID- 20701403
TI  - Tramadol/paracetamol fixed-dose combination: a review of its use in the
      management of moderate to severe pain.
AB  - Tramadol/paracetamol 37.5 mg/325 mg (Tramacet, Zaldiar, Ixprim, Kolibri) is an
      orally administered fixed-dose combination of the atypical opioid tramadol and
      paracetamol, which is indicated in the EU for the symptomatic treatment of
      moderate to severe pain. This article reviews the pharmacological properties,
      clinical efficacy and tolerability of tramadol/paracetamol in adults with
      moderate to severe pain. Fixed-dose tramadol/paracetamol is a rapidly-acting,
      longer-duration, multimodal analgesic, which is effective and generally well
      tolerated in patients with moderate to severe pain. In several well designed,
      clinical studies, single- or multiple-dose tramadol/paracetamol was effective in
      providing pain relief in adult patients with postoperative pain after minor
      surgery, musculoskeletal pain (acute, subacute or chronic), painful diabetic
      peripheral neuropathy or migraine pain. It was also effective as an add-on
      analgesic in patients who were experiencing moderate to severe musculoskeletal
      pain (e.g. osteoarthritis or rheumatoid arthritis pain) despite ongoing NSAID
      and/or disease-modifying antirheumatic drug therapy. Moreover, in patients with
      postoperative pain, ankle sprain pain or subacute lower back pain, the analgesic
      efficacy of tramadol/paracetamol was better than that of paracetamol, generally
      similar to, or better than that, of tramadol, and generally similar to that of
      ibuprofen or the fixed-dose combinations hydrocodone/paracetamol,
      codeine/paracetamol and codeine/paracetamol/ibuprofen. In addition, the analgesic
      efficacy of tramadol/paracetamol did not differ significantly from that of
      gabapentin in patients with chronic pain associated with diabetic peripheral
      neuropathy. Tramadol/paracetamol had no additional tolerability issues relative
      to its components and, overall, the tolerability profile of tramadol/paracetamol
      was generally similar to that of other active comparators (fixed-dose
      combinations or single-agents); however, incidences of some adverse events were
      lower in tramadol/paracetamol than in active comparator recipients. Although
      additional comparative and long-term studies would help to definitively position
      tramadol/paracetamol with respect to other analgesics, available clinical data
      suggest that tramadol/paracetamol is a useful treatment option for providing
      multimodal analgesia in patients with moderate to severe pain.

PMID- 20701404
TI  - Angiotensin receptor blockers and the risk of malignancy: a note of caution.

PMID- 20701405
TI  - Medications and glucose-6-phosphate dehydrogenase deficiency: an evidence-based
      review.
AB  - Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human
      enzyme defect and one of the most common genetic disorders worldwide, with an
      estimated 400 million people worldwide carrying a mutation in the G6PD gene that
      causes deficiency of the enzyme. Although drug-induced haemolysis is considered
      the most common adverse clinical consequence of G6PD deficiency, significant
      confusion exists regarding which drugs can cause haemolytic anaemia in patients
      with G6PD deficiency. In the absence of consensus among physicians, patients are
      subject to conflicting advice, causing uncertainty and distress. In the current
      review we aimed, by thorough search of the medical literature, to collect
      evidence on which to base decisions either to prohibit or allow the use of
      various medications in patients with G6PD deficiency. A literature search was
      conducted during May 2009 for studies and case reports on medication use and G6PD
      deficiency using the following sources: MEDLINE (1966-May 2009), PubMed (1950-May
      2009), the Cochrane database of systematic reviews (2009), and major
      pharmacology, internal medicine, haematology and paediatric textbooks. After
      assessing the literature, we divided medications into one of three groups:
      medications that should be avoided in individuals with G6PD deficiency,
      medications that were considered unsafe by at least one source, but according to
      our review can probably be given safely in normal therapeutic dosages to
      individuals with G6PD deficiency as evidence does not contravene their use, and
      medications where no evidence at all was found to contravene their use in G6PD
      deficient patients. It is reasonable to conclude that, over time, many compounds
      have been wrongly cited as causing haemolysis because they were administered to
      patients experiencing an infection-related haemolytic episode. We found solid
      evidence to prohibit only seven currently used medications: dapsone,
      methylthioninium chloride (methylene blue), nitrofurantoin, phenazopyridine,
      primaquine, rasburicase and tolonium chloride (toluidine blue). Regarding all
      other medications, our review found no evidence to contravene their use in normal
      therapeutic doses to G6PD-deficient patients. There is a need for evidence-based
      global consensus regarding medication use in G6PD-deficient patients.

PMID- 20701406
TI  - Lactic acidosis induced by metformin: incidence, management and prevention.
AB  - Lactic acidosis associated with metformin treatment is a rare but important
      adverse event, and unravelling the problem is critical. First, this potential
      event still influences treatment strategies in type 2 diabetes mellitus,
      particularly in the many patients at risk of kidney failure, in those presenting
      contraindications to metformin and in the elderly. Second, the relationship
      between metformin and lactic acidosis is complex, since use of the drug may be
      causal, co-responsible or coincidental. The present review is divided into three
      parts, dealing with the incidence, management and prevention of lactic acidosis
      occurring during metformin treatment. In terms of incidence, the objective of
      this article is to counter the conventional view of the link between metformin
      and lactic acidosis, according to which metformin-associated lactic acidosis is
      rare but is still associated with a high rate of mortality. In fact, the direct
      metformin-related mortality is close to zero and metformin may even be protective
      in cases of very severe lactic acidosis unrelated to the drug. Metformin has also
      inherited a negative class effect, since the early biguanide, phenformin, was
      associated with more frequent and sometimes fatal lactic acidosis. In the second
      part of this review, the objective is to identify the most efficient patient
      management methods based on our knowledge of how metformin acts on
      glucose/lactate metabolism and how lactic acidosis may occur (at the organ and
      cellular levels) during metformin treatment. The liver appears to be a key organ
      for both the antidiabetic effect of metformin and the development of lactic
      acidosis; the latter is attributed to mitochondrial impairment and subsequent
      adenosine triphosphate depletion, acceleration of the glycolytic flux, increased
      glucose uptake and the generation of lactate, which effluxes into the circulation
      rather than being oxidized further. Haemodialysis should systematically be
      performed in severe forms of lactic acidosis, since it provides both symptomatic
      and aetiological treatment (by eliminating lactate and metformin). In the third
      part of the review (prevention), the objective is to examine the list of
      contraindications to metformin (primarily related to renal and cardiovascular
      function). Diabetes is above all a vascular disease and metformin is a vascular
      drug with antidiabetic properties. Given the importance of the liver in lactate
      clearance, we suggest focusing on the severity of and prognosis for liver
      disease; renal dysfunction is only a prerequisite for metformin accumulation,
      which may only be dangerous per se when associated with liver failure. Lastly, in
      view of metformin's impressive overall effectiveness profile, it would be
      paradoxical to deny the majority of patients with long-established diabetes
      access to metformin because of the high prevalence of contraindications. The
      implications of these contraindications are discussed.

PMID- 20701407
TI  - Identifying major congenital malformations in the UK General Practice Research
      Database (GPRD): a study reporting on the sensitivity and added value of
      photocopied medical records and free text in the GPRD.
AB  - BACKGROUND: Postmarketing teratogen surveillance is essential and requires a data
      source that can reliably capture a wide range of congenital malformations. The UK
      General Practice Research Database (GPRD) may have the potential to be used for
      this kind of surveillance. OBJECTIVE: To assess the extent to which this database
      can be used to accurately identify major congenital malformations. METHODS: This
      study was carried out as part of a broader study to compare data on
      anticonvulsant use and safety in pregnancy between the GPRD and a pregnancy
      registry. The study period ran from 1 January 1990 until 31 December 2006. Mother
      baby pairs where the mother had a record of epilepsy, seizure or convulsion were
      identified using the GPRD computerized medical records. Infants of mother-baby
      pairs who had a record of a major congenital malformation were identified. Full
      photocopied paper medical records were requested from the infant's general
      practitioner and where this was not possible any data entries consisting of
      uncoded comments, so-called 'free text', in the electronic GPRD record were
      requested from the database provider. This additional information was then
      reviewed in order to determine the extent to which the congenital malformation
      diagnoses identified via the computerized records could be confirmed or rejected
      and then classified as being major or minor. RESULTS: Within the study population
      of 3869 live mother-baby pairs, 188 potentially major congenital malformations
      were identified from the GPRD computerized record relating to 161 unique
      individuals. Using a combination of photocopied medical records and free text it
      was possible to verify 160 malformations (85.1%) as the malformation indicated by
      the computerized records; this ranged from 91.7% of those cases verified using
      photocopied medical records and 77.9% of cases verified using free text. Of the
      verified congenital malformations, using a combination of computerized data,
      photocopied medical records and free text, it was possible to classify 78.1% as
      being major and 15.0% as minor, and this percentage was found to be the same for
      those cases reviewed by photocopied records and those where free text was used.
      The proportions of malformations that could be verified and those that could be
      classified as major or minor were found to vary by malformation class.
      CONCLUSIONS: The GPRD can be used to ascertain a wide range of congenital
      malformations. In many cases, when a malformation is identified in the GPRD via
      the computerized medical records, the malformation is likely to exist. However,
      in this study a small proportion of identified cases had to be excluded because
      they had been coded incorrectly or diagnostically ruled out. Therefore, depending
      on the congenital malformation of interest, verification of such malformations
      using photocopied medical records or free text is generally recommended.

PMID- 20701408
TI  - Paediatric postmarketing pharmacovigilance using prescription-event monitoring:
      comparison of the adverse event profiles of lamotrigine prescribed to children
      and adults in England.
AB  - BACKGROUND: Using postmarketing pharmacovigilance data collected shortly after
      market authorization of lamotrigine in the UK, a study was conducted to compare
      the adverse event (AE) profiles of children and adults taking lamotrigine, using
      modified signal detection methods. METHODS: Data from the lamotrigine
      Prescription Event Monitoring (PEM) study, an observational cohort study, were
      stratified by age and examined using summary statistics for adverse drug
      reactions (ADRs), reasons for stopping treatment, deaths and follow-up
      information. Incidence densities of AEs in children (0-17 years) and adults (> or
      =18 years) in the first month of treatment were compared with months 2-6 to
      examine whether the AE rates were different in these two periods. AE rates in
      children were compared with those in adults (proportional reporting ratio [PRR]
      and incidence rate ratios), to compare the AE profiles between these age groups.
      RESULTS: The cohort included 2457 children and 7379 adults. Differences in the AE
      profiles between children and adults were observed. Rash (PRR 1.2) and Stevens
      Johnson syndrome (PRR 4.5) were more commonly reported in children, and confusion
      more frequently in adults (PRR 6.3). In children, 33% of ADRs were reported to
      the Regulatory Authority compared with 44% in adults. A higher proportion of
      children stopped treatment due to lack of effectiveness (45% vs 38%). No deaths
      were attributed to lamotrigine. CONCLUSIONS: This study demonstrated that signal
      detection methods can be used to detect quantitative and qualitative differences
      in the AE profiles between the first children and adults taking a newly licensed
      drug.

PMID- 20701409
TI  - Completeness of published case reports on suspected adverse drug reactions:
      evaluation of 100 reports from a company safety database.
AB  - BACKGROUND: Case reports of suspected adverse drug reactions (ADRs) are common in
      the biomedical literature. Standards for authors and editors for writing,
      submitting and publishing ADR case reports have been empirically established
      since the 1980s; however, these recommendations have not been widely disseminated
      or incorporated into practice. Comprehensive and standardized guidelines on good
      publication practice have recently been proposed. No study has been performed so
      far to assess the adherence of published ADR case reports to these guidelines.
      OBJECTIVE: To describe the current situation with regards to the reliability and
      completeness of published ADR case reports. METHODS: A random sample of 100
      single ADR case reports published between 2005 and 2008 (25 for each year) was
      retrieved from Pfizer's pharmacovigilance database. Reliability and completeness
      were assessed by comparing the relevant information contained in the retrieved
      ADR case reports against the recommendations prescribed by the guidelines.
      Descriptive statistics and correlation analysis using the Statistical Package for
      Social Science (SPSS) were undertaken. RESULTS: The patient's medical history
      relevant to the ADR was reported in 92% of the case reports. Concerning the
      suspected drug, 11% of the reports included the proprietary name; duration,
      dosage, route and formulation were reported in 87%, 85%, 37% and 21% of the
      reports, respectively. Information on concomitant therapies was included in 71%
      of the reports. The description of the ADR contained details on management (99%),
      time-course (97%) and diagnostic tests (95%), while final outcome and seriousness
      were reported in 73% and 52% of the reports, respectively. A discussion on the
      possible mechanism for the ADR was present in 70% of the case reports. The
      possible implications for clinical practice of the reported drug-event
      association were described in 75% of the cases. Causality assessment was reported
      in 81%, and rating scales to support the causal link were used in 20% of the
      reports. The major predictive factor for the presence of an objective causality
      assessment was found to be publication in specialized pharmacoepidemiology or
      clinical pharmacology journals: 47% specialized versus 11% non-specialized (odds
      ratio = 6.93; 95% CI 2.37, 20.26). CONCLUSIONS: The findings of this study show
      that published ADR case reports, especially those coming from non-specialized
      journals, still lack important information necessary for comprehensive
      evaluation. As published ADR case reports are expected to be reported to
      regulatory authorities using the same approach as for spontaneous cases, it is
      paramount for their effective integration in the pharmacovigilance system that
      pharmaceutical companies and learned societies actively promote a culture of good
      publication practices.

PMID- 20701410
TI  - Adverse drug reaction reporting in the UK: a retrospective observational
      comparison of yellow card reports submitted by patients and healthcare
      professionals.
AB  - BACKGROUND: In the UK, spontaneous reporting of suspected adverse drug reactions
      (ADRs) by healthcare professionals has been in operation since 1964 through the
      Yellow Card Scheme (YCS). From 2005, patients themselves have been able to submit
      Yellow Card reports. OBJECTIVE: To compare patient characteristics, suspected
      drugs and suspected ADRs reported by patients with those reported by healthcare
      professionals using the YCS. DESIGN AND SETTING: Retrospective observational
      study in the UK. METHODS: Participants were patients reported to the Medicines
      and Healthcare products Regulatory Agency (MHRA), either by themselves, a
      representative or a healthcare professional, as having one or more suspected ADRs
      between October 2005 and September 2007. The main outcome measures were ADRs and
      time taken to report. RESULTS: In total, 26 129 Yellow Card reports from patients
      and healthcare professionals were received from the MHRA for the 2-year study
      period (19.8% patient and 80.2% healthcare professional). More Yellow Card
      reports were made for female than male patients (p < 0.001). Patients reported a
      significantly higher number of suspected ADRs per report than healthcare
      professionals (median [interquartile range {IQR}] of 3 [2-5] vs 2 [1-3],
      respectively; p < 0.001). A higher proportion of patient reports (16.1%)
      contained more than one suspect drug than healthcare professional reports (9%; p
      < 0.001). Healthcare professional reports had a higher proportion of ADRs that
      caused hospitalization (18.8% vs 12.9%), were life threatening (11.1% vs 6.2%) or
      caused death (2.6% vs 0.7%) than patient reports (all p < 0.001). Patient
      reporters took a significantly longer time to report their reaction than
      healthcare professionals (median [IQR] of 104 [27-463] vs 28 [13-75] days
      respectively; p < 0.001). Direct comparisons of the seriousness of the ADRs were
      not possible because of important differences between patient and healthcare
      professional versions of the Yellow Cards. CONCLUSIONS: This is the first
      substantial, published study in the UK to compare Yellow Card reports from
      patients and healthcare professionals. Whilst patients report more suspected ADRs
      to more suspect drugs than healthcare professionals, healthcare professionals
      tend to report more serious reactions that result in hospitalization, are life
      threatening or cause death. Further research is required to investigate the
      extent to which the extra information from patient reporters contributes to
      signal identification when assessing drug safety.

PMID- 20701411
TI  - Safety profile of the fluoroquinolones: analysis of adverse drug reactions in
      relation to prescription data using four regional pharmacovigilance databases in
      Italy.
AB  - BACKGROUND: Fluoroquinolones are widely used both in primary care and in hospital
      settings. Since the last comparison performed in Italy on the safety profiles of
      different fluoroquinolones, a new molecule, prulifloxacin, has been introduced
      into the market and several warnings concerning this class of drugs have been
      released. The aim of this study was to reassess the safety profiles of
      fluoroquinolones using the database of the Italian Interregional Group of
      Pharmacovigilance (IGP) and the administrative data of fluoroquinolone
      prescriptions. METHODS: All adverse drug reactions (ADRs) reported in four
      Italian regions (Lombardy, Veneto, Emilia Romagna and Tuscany) were retrieved
      from the IGP database. Consumption data (defined daily dose [DDD]/1000
      inhabitants/day) were used as denominators. Both single reports and all ADRs
      (classified by System Organ Classes and MedDRA Preferred Term [PT]) due to
      fluoroquinolones were considered as numerators of each analysis, comparing two
      periods (2005 vs 2006). All fluoroquinolones with at least ten reports per year
      were included in the analysis. RESULTS: On the basis of 272 reports (532 single
      ADRs or PTs), patients did not show any statistically significant differences
      between 2005 and 2006 in terms of sex, age and number of concurrent medications.
      After adjustment for drug consumption, moxifloxacin showed the highest reporting
      rate (84.6 reports/DDD/1000 inhabitants/day; 15.4 serious reports/DDD/1000
      inhabitants/day) followed by prulifloxacin (72.2; 22.2 serious) and levofloxacin
      (55.3; 30.6 serious) in 2005. An increment of ADR/report rates was observed over
      the 2 years for all fluoroquinolones except prulifloxacin, which had the lowest
      ADR reporting rate in 2006 (25.0; 12.5 serious). In 2006, the rate of serious
      ADRs associated with prulifloxacin was lower than with ciprofloxacin, while in
      2005 serious events were almost equal for both compounds (55.6 vs 47.6 serious
      ADRs/DDD/1000 inhabitants/day). Ciprofloxacin showed the highest proportion of
      cutaneous PTs (e.g. rash, exanthema). Tendinopathies were mainly due to
      levofloxacin. CONCLUSIONS: These data suggest that different fluoroquinolones are
      characterized by different rates and types of ADRs. Among them, prulifloxacin was
      associated with more ADRs than other fluoroquinolones in 2005 but with fewer ADRs
      in 2006, when its consumption increased. Although these findings may represent an
      encouraging perspective towards a more appropriate use of fluoroquinolones
      because of their individual safety profiles, further pharmacoepidemiological
      studies must be performed to substantiate these results.

PMID- 20701412
TI  - Health worker effectiveness and retention in rural Cambodia.
AB  - INTRODUCTION: A decade after health sector reform, public health services in
      rural Cambodia remain under-utilised for multiple reasons related to financial,
      structural and personnel factors. Ineffectiveness of rural public health services
      has led to a significant increase in private providers, often the same people who
      staff public facilities. Public health clinics are often portrayed as low
      quality, with long waiting times and unexpected costs; in contrast, private
      clinics are seen to provide more convenient health care. Several strategies,
      including contract management and health equity funds, have been introduced to
      improve public sector performance and encourage utilization; these efforts are
      ongoing. However, the feasibility of these strategies remains in question,
      particularly in terms of cost-effectiveness and sustainability. METHODS: In this
      article the strategies of and barriers met by health workers who remain in rural
      areas and deliver public health services are elucidated. Ethnographic research
      conducted in 2008 with health providers involved in treating tuberculosis
      patients in Kampong Speu Province, Cambodia is drawn on. Participants were
      recruited from the provincial health department, provincial hospital and four
      health centres. Data collection involved in-depth interviews, participation in
      meetings and workshops aimed at health workers, and observation of daily
      activities at the health facilities. Data were transcribed verbatim, imported
      into NVivo software (www.qsrinternational.com) for management, and analysed using
      a grounded theory approach. RESULTS: Primary healthcare service delivery in rural
      Cambodia was reliant on the retention of mid-level of health staff, primarily
      midwives and nurses. Its performance was influenced by institutional
      characteristics relating to the structure of the health system. Personal factors
      were impacted on by these structural issues and affected the performance of
      health staff. Institutional factors worked against the provision of high-quality
      public health services, and included the fragmentation of service delivery and
      structure, limited capacity and shortage of high-qualified health staff,
      competition with the private sector, and shortage of medical supplies. These
      factors all de-motivated health staff, and undermined their performance in public
      service positions. Personal factors were paramount for staff retention. These
      included: optimism and appreciation of work responsibilities and position, the
      personal ability to cope with financial barriers, and institutional benefits such
      as opportunities for professional development, job security, financial
      opportunities (via performance-based allowances), and status in society.
      Individual financial coping strategies were the dominant factor underlying
      retention, but alone were often de-motivating: clients were diverted from the
      public services, which led to distrust, and thus undermined the capacity of
      public system. There was significant interaction between institutional and
      personal factors, which impacted on the effectiveness of health staff retention
      in rural areas. Health workers tended to remain in their government positions for
      prolonged periods of time because they experienced personal rewards. At the same
      time, however, their job performance in the public health services were hindered
      by challenges related to the institutional factors. CONCLUSIONS: The interaction
      between institutional factors and personal factors was crucial for effectiveness
      of health staff retention in rural Cambodia. Efforts aimed at ensuring quality of
      care and encouraging health staff retention should attempt to remove the
      institutional barriers that discourage the use of rural public health services.

PMID- 20701413
TI  - Growing up in rural community--children's experiences of social capital from
      perspectives of wellbeing.
AB  - INTRODUCTION: People are influenced by the neighborhood in which they live. The
      neighborhood may be particularly important for children's wellbeing because of
      the constraints it imposes on their patterns of daily activities. Furthermore,
      the neighborhood is a central context for social development, being a place where
      children form networks and learn social skills and values. The aim of this study
      was to describe how social capital in the neighborhood is perceived by children
      living in rural areas, and to reveal what this adds to their sense of wellbeing.
      METHODS: The study had a descriptive research design with a qualitative approach.
      Seven single-sex focus group interviews were conducted with children the in 6th
      grade (aged 11-12 years). Data were analyzed using deductive content analysis.
      RESULTS: The children perceived a lack of social capital due to environmental and
      social constraints in their everyday lives. However, their wellbeing was enhanced
      by strong cohesion in the neighborhood. In addition, settings such as the school,
      the natural environment, and sporting associations were highly valued and emerged
      as crucial factors for enhancing the children's wellbeing. The spatial isolation
      that characterizes rural areas created a special context of social network
      structures, cohesion and trust, but was also a breeding ground for exclusion and
      social control. The stories revealed paradoxical feelings of living in a good and
      safe area that simultaneously felt isolated and restricted. CONCLUSIONS: From a
      rural perspective, this study reveals the complexity of the children's
      perceptions of their social environment, and the ways in which these perceptions
      have both positive and negative effects on wellbeing. The results highlight how
      important it is for health professionals in rural areas to consider the complex
      influence of bonding social capital on children's wellbeing, and to be aware that
      it can promote exclusion as well as cohesion.

PMID- 20701414
TI  - Major incidents in rural areas: managing a pandemic A/H1N1/2009 cluster.
AB  - CONTEXT: Pandemic Influenza (A/H1N1/2009) caused worldwide concern because of its
      potential to spread rapidly in human populations. In Scotland, Government policy
      had been to seek to contain the spread of the virus for as long as possible in
      order to allow time for service preparations, and for vaccine development and
      supply. ISSUE: The first major Scottish outbreak of pandemic A/H1N1/2009 was in
      the rural area of Cowal and Bute. After two initial cases were identified,
      contact tracing found a cluster of cases associated with a football supporters'
      bus. Within 3 weeks, 130 cases had been identified in the area. Rapid provision
      of treatment doses of anti-viral medication to cases and prophylactic treatment
      of asymptomatic close contacts, advice on self-isolation and, where required,
      interruption of transmission by temporary school closure, were successful in
      containing the outbreak. LESSONS LEARNED: Pre-existing Major Incident and
      Pandemic Flu plans were used and adapted to the particular circumstances of the
      outbreak and the area. Supporting operational decision-making as close to the
      cases as possible allowed for speed and flexibility of response. Contact tracing
      and tracking of cases and results was performed by specialist public health staff
      who were geographically removed from the cases. This was possible because of
      effective use of existing telephone conferencing facilities, clarity of roles,
      and frequent communication among staff working on all areas of the response.
      Basing the work on established plans, staff experience of rural areas and rural
      service provision was successful.

PMID- 20701415
TI  - The Station Community Mental Health Centre Inc: nurturing and empowering.
AB  - INTRODUCTION: Consumer-driven community mental health services play an important
      role in rehabilitation, recovery, and advocacy in rural and remote Australia. The
      origins of services often lie in the need to provide options for people with
      mental illness and their carers when there is a lack of on-the-ground support.
      This article adds to the information about the strengths and limitations of
      consumer-driven mental health services by presenting the findings of an
      evaluation of The Station Inc. in rural South Australia. This consumer-driven
      mental health service provides a safe and supportive environment, social
      connections, and activities for its members (those with a lived experience of
      mental illness). Using a realist evaluation approach, the evaluation identified
      the contextual factors and the program mechanisms that produce positive outcomes
      for members. METHOD: The evaluation was conducted as participatory action
      research with The Station members, volunteers, management committee members, and
      staff involved in all phases of the research process. Because of the complexity
      of The Station's functioning a realist evaluation using qualitative data was
      conducted to identify how the program worked, for whom, and in what
      circumstances. Twenty-five in-depth interviews were conducted with participants
      who were randomly selected from within the groups identified above. Interviews
      focused on The Station's role in assisting recovery from mental illness, the
      limitations and strengths of the program, and relationships with the mental
      health system. The Station's goals, policies and procedures, and the role of
      stakeholders were analysed in order to identify any links among these contextual
      factors, program mechanisms, and program outcomes. Qualitative data were entered
      into descriptive categories in N6 software (QSR; <a
      href="http://www.qsr.international.com"
      target="_blank">www.qsr.international.com). Data from the stakeholder analysis
      were entered into Microsoft Excel. Using an iterative approach to include the
      three data sets, a model was developed that identified important contextual
      factors that linked with two groups of program mechanisms that produced positive
      outcomes for members. RESULTS: Program mechanisms are categorised by descriptive
      themes referred to as 'nurturing' and 'empowering'. Nurturing' is experienced as
      feeling of belonging and being accepted 'as one is' and 'empowerment' mechanisms
      engender a belief in oneself. Respondents identified features of The Station's
      program, policies, atmosphere, connections and networks, stakeholder
      relationships, and staff and volunteers that are nurturing and empowering. Five
      key contextual factors enable the program mechanisms to work. The Station's
      coordinators ensure that nurturing and empowerment processes are highlighted
      through careful facilitation. The governance arrangements, policies, and
      administrative systems at The Station are well developed but flexibly implemented
      so that they support the nurturing and empowerment processes. Support and
      legitimacy for the program is obtained from the mental health system at state and
      local levels. The Station obtains resources and connections to its rural
      community through key stakeholders and a peak organisation One Voice Network acts
      as an advocate. CONCLUSIONS: Information about the benefits and limitations of
      consumer-driven mental health services in rural and remote Australia is in short
      supply. Increasing the available information about the contribution these
      services make may result in services being legitimised, understood, and resourced
      within mental health systems thus making the services sustainable. The benefits
      of consumer-driven services are that they provide flexibility and adaptation, an
      ability to capture the energy and passion of rural communities to improve the
      wellbeing of community members, and they overcome the power differential that
      exists between professionals and 'patients' or 'clients'.

PMID- 20701416
TI  - A novel approach to decreasing bullying.

PMID- 20701417
TI  - Children who witness violence: what services do they need to heal?
AB  - Children are witnesses to violence far too often in their daily lives. To elicit
      information on the needs of children and adolescents living in the United States
      who have witnessed violence in their homes, neighborhoods, or communities, we
      held focus groups with mothers who have survived interpersonal violence and whose
      family included child witnesses to violence (CWV), professionals who work with
      families affected by violence, and with adolescents who have witnessed violence.
      Based on four separate focus group discussions held in Massachusetts, involving a
      total of 45 participants, recommendations for screening, programming, and the
      development of healing interventions are offered to mental health professionals.

PMID- 20701418
TI  - Occupational stressors and the mental health of truckers.
AB  - Trucking has been classified as one of the highest-risk occupations in the United
      States. Occupational stress is even greater for long-haul truckers who are away
      from home, family, friends, and other support networks for several days or weeks
      at a time. Occupational stressors and the mental health of truckers was studied
      using data collected as part of a large multisite ethno-epidemiological study of
      trucker networks. Findings from the current study show that truckers face many
      occupational stressors including constant time pressures, social isolation,
      disrespectful treatment from others, driving hazards such as weather changes,
      traffic, and road conditions, and violence or fear of violence. Facing such
      stressors may be a factor in the prevalence of risky behaviors including drug use
      and paying for sex. Therefore, mental health promotion and treatment for truckers
      is an important area of concern and must be examined within the broader context
      of the transportation environment.

PMID- 20701419
TI  - Using the tidal model of mental health recovery to plan primary health care for
      women in residential substance abuse recovery.
AB  - Women currently are 30% of the substance abuse recovery population in North
      America and have gender specific treatment needs as they enter the difficult work
      of recovery. Important among women's specific needs as they enter recovery is the
      need for a focus on primary health care. Few models designed to guide the
      provision of health care for this population are available in the literature. The
      Tidal Model of Mental Health Recovery and Reclamation is based on the concept of
      nursing as "caring with" persons in the experience of distress. Given the
      emphasis in this model on developing a partnership between caregiver and client,
      it is especially appropriate for women in recovery for substance abuse. The Tidal
      Model, integrated with the United States Substance Abuse and Mental Health
      Services' CSAT model for comprehensive alcohol and other drug (AOD) abuse
      treatment, is used to guide planning for delivery of primary health care in a
      residential women's substance abuse recovery center in the Midwest. This article
      describes the Tidal Model, and identifies how the model can improve the delivery
      of primary care to women in residential substance abuse treatment. Strategies for
      implementation of the model are proposed. Evaluation and outcome criteria are
      identified.

PMID- 20701420
TI  - Bi-dimensional acculturation and cultural response set in CES-D among Korean
      immigrants.
AB  - This study examined a cultural response set to positive affect items and
      depressive symptom items in CES-D among 172 Korean immigrants. Bi-dimensional
      acculturation approach, which considers maintenance of Korean Orientation and
      adoption of American Orientation, was utilized. As Korean immigrants increased
      their American Orientation, they tended to score higher on positive affect items,
      with no changes occurring in depressive symptom items. Korean Orientation was not
      related to either positive affect items or depressive symptom items. Korean
      immigrants have a response bias toward positive affect items in CES-D, which
      decreases as they adopt more American Orientation. CES-D lacks cultural
      equivalence for Korean immigrants.

PMID- 20701421
TI  - Relationships between depressive symptoms and perceived social support, self
      esteem, & optimism in a sample of rural adolescents.
AB  - Stress, developmental changes and social adjustment problems can be significant
      in rural teens. Screening for psychosocial problems by teachers and other school
      personnel is infrequent but can be a useful health promotion strategy. We used a
      cross-sectional survey descriptive design to examine the inter-relationships
      between depressive symptoms and perceived social support, self-esteem, and
      optimism in a sample of rural school-based adolescents. Depressive symptoms were
      negatively correlated with peer social support, family social support, self
      esteem, and optimism. Findings underscore the importance for teachers and other
      school staff to provide health education. Results can be used as the basis for
      education to improve optimism, self-esteem, social supports and, thus, depression
      symptoms of teens.

PMID- 20701422
TI  - Peer support among inpatients in an adult mental health setting.
AB  - Existing literature indicates peer support is beneficial for people with mental
      illnesses and plays an important role in recovery. While many studies in the
      mental health field have focused on formalized peer support within the community,
      none have explored the experience of peer support among hospitalized patients.
      The purpose of the current study was to explore the perceptions and experiences
      of naturally occurring peer support among adult mental health inpatients. In
      depth interviews were conducted with ten inpatients across four mental health
      units, two acute and two long-term. Interviews were transcribed verbatim and
      analyzed using a qualitative descriptive design. The data show that peer support
      among inpatients is extensive and beneficial, and occurs independently of staff
      involvement. The findings illustrate that peer support is a thoughtful process
      that involves observing, reflecting, taking action, and evaluating outcomes.
      Supportive actions include helping with activities of daily living, sharing
      material goods, providing information and advice, sharing a social life, and
      offering emotional support. This leads to various positive outcomes for providers
      and recipients of peer support, such as improved mental health outcomes and
      quality of life. Attempts to provide supportive interactions occur within a
      particular context, which can hinder or facilitate peer support. The new insights
      from this study could provide health professionals with an increased recognition
      of peer support and an appreciation for the unique role patients play in their
      own and in their peers' recovery. These findings have important implications for
      establishing collaborative working partnerships with mental health inpatients.

PMID- 20701423
TI  - Aggressive events in adolescent dating violence.
AB  - This purpose of this paper is to present a typology of common aggressive events
      that occur in the context of adolescent dating violence. The typology is based on
      42 transcripts of interviews with young adults, ages 18 to 21, who described
      dating violence they had experienced when adolescents (ages 13-18). One-hundred
      and eighty-four text units that contained a description of an event involving
      aggression or violence between the participant and a dating partner were
      extracted from the transcripts. Cross-case analysis was used to create categories
      of events that shared similar characteristics. The analysis yielded eight types
      of aggressive events: (a) tumultuous, (b) explosive, (c) scuffling, (d)
      violating, (e) threatening, (f) controlling, (g) disparaging, and (h) rejecting,
      ignoring, or disrespecting. The typology can provide a foundation for further
      research on adolescent dating violence from a situational perspective and can be
      used as a tool to promote discussion of dating violence with victimized or at
      risk youth.

PMID- 20701424
TI  - Community tailored responses to depression care.

PMID- 20701425
TI  - "Psychiatric/mental health nursing" or "psychiatric-mental health nursing"?

PMID- 20701426
TI  - Treatments for childhood ADHD part II: non-pharmacological and novel treatments.

PMID- 20701428
TI  - Development and characterization of a Versatile Engineered Nanomaterial
      Generation System (VENGES) suitable for toxicological studies.
AB  - A novel system for generation of engineered nanomaterials (ENMs) suitable for in
      situ toxicological characterization within biological matrices was developed.
      This Versatile Engineered Nanomaterial Generation System (VENGES) is based on
      industry-relevant, flame spray pyrolysis aerosol reactors that can scaleably
      produce ENMs with controlled primary and aggregate particle size, crystallinity,
      and morphology. ENMs are produced continuously in the gas phase, allowing their
      continuous transfer to inhalation chambers, without altering their state of
      agglomeration. Freshly generated ENMs are also collected on Teflon filters for
      subsequent physicochemical and morphological characterization and for in vitro
      toxicological studies. The ability of the VENGES system to generate families of
      ENMs of pure and selected mixtures of iron oxide, silica, and nanosilver with
      controlled physicochemical properties was demonstrated using a range of state-of
      the-art-techniques. Specific surface area was measured by nitrogen adsorption
      using the Brunauer-Emmett-Teller method, and crystallinity was characterized by X
      ray diffraction. Particle morphology and size were evaluated by scanning and
      transmission electron microscopy. The suitability of the VENGES system for
      toxicological studies was also shown in both in vivo and in vitro studies
      involving Sprague-Dawley rats and human alveolar-like monocyte derived
      macrophages, respectively. We demonstrated linkage between physicochemical ENM
      properties and potential toxicity.

PMID- 20701430
TI  - Repetitive intrathecal VEGF(165) treatment has limited therapeutic effects after
      spinal cord injury in the rat.
AB  - Neuropathic pain and motor deficits are detrimental consequences of injury to the
      spinal cord. In experimental settings, numerous neuroprotective agents are being
      explored for their therapeutic benefits. Vascular endothelial growth factor
      (VEGF) is an interesting candidate molecule in this respect since it is not only
      associated with angiogenesis, but also with neuroprotection and neurite growth.
      Other investigators have reported improved motor outcomes following
      intraparenchymal VEGF treatment. Here we demonstrate the therapeutic effects of
      daily intrathecal treatment of the contused thoracic rat spinal cord with the 165
      isoform of VEGF during the first week after injury. We show that VEGF treatment
      resulted in a statistically significant attenuation of mechanical, but not
      thermal, hypersensitivity of the hindpaws, while motor deficits remained
      unaffected. Tissue sparing was also unchanged by VEGF treatment. Microglial
      responses at the lumbar spinal cord, which have been linked with spinal cord
      injury-induced hypersensitivity, were found to be unaffected by VEGF treatment.
      We conclude that repetitive intrathecal VEGF delivery has limited therapeutic
      effects on spinal cord injury outcome.

PMID- 20701429
TI  - Enhanced ROS generation mediated by Alzheimer's disease presenilin regulation of
      InsP3R Ca2+ signaling.
AB  - Familial Alzheimer's disease (FAD) is caused by mutations in amyloid precursor
      protein and presenilins (PS1, PS2). Many FAD-linked PS mutations affect
      intracellular calcium (Ca(2+)) homeostasis by proximal mechanisms independent of
      amyloid production by dramatically enhancing gating of the inositol trisphosphate
      receptor (InsP(3)R) intracellular Ca(2+) release channel by a gain-of-function
      effect that mirrors genetics of FAD and is independent of secretase activity.
      Electrophysiological recordings of InsP(3)R in FAD patient B cells, cortical
      neurons of asymptomatic PS1-AD mice, and other cells revealed they have higher
      occupancy in a high open probability burst mode, resulting in enhanced Ca(2+)
      signaling. Exaggerated Ca(2+) signaling through this mechanism results in
      enhanced generation of reactive oxygen species, believed to be an important
      component in AD pathogenesis. Exaggerated Ca(2+) signaling through InsP(3)R-PS
      interaction is a disease specific and robust proximal mechanism in AD that may
      contribute to the pathology of AD by enhanced generation of reactive oxygen
      species.

PMID- 20701431
TI  - Stroke survivors' experiences of rehabilitation: a systematic review of
      qualitative studies.
AB  - INTRODUCTION: The aim was to obtain the best available knowledge on stroke
      survivors' experiences of rehabilitation. The increase in demands for
      accountability in health care and acknowledgement of the importance of client
      participation in health decisions calls for systematic ways of integrating this
      perspective. METHODS AND MATERIALS: A systematic review of qualitative studies
      was performed. A literature search in MEDLINE, CINAHL, PsycINFO, and EMBASE was
      conducted. Suitability for inclusion was based on selected criteria: published
      qualitative studies written in English from 1990 to 2008 on stroke survivors'
      experiences of rehabilitation in a clinical setting. Data analysis entailed
      extracting, editing, grouping, and abstracting findings. RESULTS: Twelve studies
      were included. One theme, "Power and Empowerment" and six subcategories were
      identified: 1) Coping with a new situation, 2) Informational needs, 3) Physical
      and non-physical needs, 4) Being personally valued and treated with respect, 5)
      Collaboration with health care professionals and 6) Assuming responsibility and
      seizing control. DISCUSSION: The synthesis showed that stroke survivors'
      experiences of rehabilitation reflected individual and relational aspects of
      power and empowerment. The capacity to assume power and empowerment was a dynamic
      rather than a progressive issue, and enabling empowerment was a matter of
      weighing contrasting issues against each other, e.g. the right to decide versus
      the right not to decide.

PMID- 20701432
TI  - The 6-month persistence on SSRIs and associated economic burden.
AB  - OBJECTIVES: To assess persistence on SSRIs (most prescribed antidepressants) and
      associated healthcare costs in a naturalistic setting. METHODS: For this
      retrospective cohort study based on a US reimbursement claims database, all
      adults with a claim for a SSRI (citalopram, escitalopram, fluoxetine, paroxetine
      or sertraline) related to a diagnosis of depression were included. Patients
      should have had no previous reimbursement for any antidepressant within the
      previous 6 months. Non-persistence was defined as failing to renew prescription
      within 30 days in the 6-month period after the index date. RESULTS: In the 45,481
      patients included, persistence decreased from 95.5% at 1 month, to 52.6% at 2
      months, 37.6% at 3 months and 18.9% at 6 months. Among factors associated with
      higher 6-month persistence were age 18-34 years, physician's specialty, treatment
      with escitalopram, absence of abuse history and psychotropic prescription
      history. During the 6-month after index date, healthcare costs tended to be
      higher in non-persistent than in persistent patients although not significantly
      (RR=1.05, adjusted p=0.055). CONCLUSION: Despite some limitations associated with
      the use of computerized administrative claims data (residual unmeasured
      confounding), these results highlight a generally low persistence rate at 6
      months. Special attention should be given to persistence on treatment, with
      consideration of potential antidepressant impact.

PMID- 20701433
TI  - Epidemiology of gastroduodenal erosions in the general population: endoscopic
      results of the systematic investigation of gastrointestinal diseases in China
      (SILC).
AB  - OBJECTIVE: Population-based endoscopic studies of gastroduodenal erosions are
      limited in the world. This study describes features of gastroduodenal erosions in
      a representative sample of the population in Shanghai, China. MATERIAL AND
      METHODS: A total of 3600 individuals (aged 18-80 years) were randomly selected
      from the Shanghai region and asked to undergo endoscopy and provide a blood
      sample to test for H. pylori infection. Participants completed a general
      information questionnaire, and a Chinese version of the Reflux Disease
      Questionnaire; 20% were also invited to complete the 36-item Short Form Health
      Survey and Epworth Sleepiness Scale. Associations between gastroduodenal erosions
      and other factors were analyzed using a multiple logistic regression model.
      RESULTS: In total, 3153 individuals (87.6%) completed the survey and provided
      blood samples, 1030 (32.7%) agreed for endoscopy and 1022 participants were
      suitable for analysis. In all, 510 participants (49.9%) had gastroduodenal
      erosions (502 with gastric erosions; 26 with duodenal erosions). No significant
      association was found between H. pylori infection and gastroduodenal erosions.
      Increasing age, increasing BMI and current smoking were independent predictors
      for the presence of gastric erosions, but not of duodenal erosions. Duodenal
      erosions were more prevalent among men, which were not found in gastric erosions.
      The majority of individuals with gastroduodenal erosions were asymptomatic.
      CONCLUSIONS: Gastroduodenal erosions are more common in China than in Europe,
      North America, and South America. No significant association was found between H.
      pylori infection and gastroduodenal erosions in China. The majority of
      individuals with gastroduodenal erosions were asymptomatic.

PMID- 20701434
TI  - Long-term effects and colectomy rates in ulcerative colitis patients treated with
      infliximab: a Danish single center experience.
AB  - OBJECTIVE: Infliximab (IFX) is a well-established treatment for both acute,
      severe ulcerative colitis (UC) and chronic, refractory UC. However, data on the
      long-term clinical outcome and colectomy rates after IFX treatment in a routine
      clinical setting are sparse. The aim of this study was to provide further data on
      the long-term effect of IFX for acute, severe and chronic, refractory UC in
      unselected patients treated at a single center. MATERIAL AND METHODS: A
      retrospective analysis of all patients (n = 52) treated with IFX for UC before
      February 2009 was performed. The material comprised 19 patients (37%) with acute,
      severe UC and 33 patients (63%) with chronic, refractory UC. The primary outcome
      was colectomy rate; the secondary outcome clinical response. RESULTS: The overall
      colectomy rate was 27% (14/52 patients) after a median follow-up of 22 months
      (range 4-57 months). The colectomy rate was 37% (7/19 patients) in the group with
      acute, severe UC and 21% (7/33 patients) among those with chronic, refractory UC.
      In all, 77% of the patients had clinical response to IFX treatment with no
      difference between the two subgroups. Among those with an initial clinical
      response, 50% (20/40 patients) had sustained clinical response. CONCLUSION: IFX
      is of long-term benefit as rescue treatment in selected patients with acute,
      severe UC with about two-thirds of the patients avoiding colectomy. The
      beneficial effect on colectomy rate in chronic, refractory UC seems less
      convincing although these patients may still achieve a sustained clinical
      response.

PMID- 20701435
TI  - An elevated fetal interleukin-6 concentration can be observed in fetuses with
      anemia due to Rh alloimmunization: implications for the understanding of the
      fetal inflammatory response syndrome.
AB  - OBJECTIVE: The fetal inflammatory response syndrome (FIRS) has been described in
      the context of preterm labor and preterm prelabor rupture of the membranes and is
      often associated with intra-amniotic infection/inflammation. This syndrome is
      characterized by systemic fetal inflammation and operationally defined by an
      elevated fetal plasma interleukin (IL)-6. The objective of this study was to
      determine if FIRS can be found in fetuses with activation of their immune system,
      such as the one observed in Rh alloimmune-mediated fetal anemia. METHODS: Fetal
      blood sampling was performed in sensitized Rh-D negative women with suspected
      fetal anemia (n=16). Fetal anemia was diagnosed according to reference range
      nomograms established for the assessment of fetal hematologic parameters. An
      elevated fetal plasma IL-6 concentration was defined using a cutoff of >11 pg/ml.
      Concentrations of IL-6 were determined by immunoassay. Non-parametric statistics
      were used for analysis. RESULTS: (1) The prevalence of an elevated fetal plasma
      IL-6 was 25% (4/16); (2) there was an inverse relationship between the fetal
      hematocrit and IL-6 concentration -- the lower the hematocrit, the higher the
      fetal IL-6 (r=-0.68, p=0.004); (3) fetuses with anemia had a significantly higher
      plasma IL-6 concentration than those without anemia (3.74 pg/ml, interquartile
      range (IQR) 1.18-2.63 vs. 1.46 pg/ml, IQR 1.76-14.7; p=0.02); (4) interestingly,
      all fetuses with an elevated plasma IL-6 concentration had anemia (prevalence
      40%, 4/10), while in the group without anemia, none had an elevated fetal plasma
      IL-6. CONCLUSIONS: An elevation in fetal plasma IL-6 can be observed in a subset
      of fetuses with anemia due to Rh alloimmunization. This observation suggests that
      the hallmark of FIRS can be caused by non-infection-related insults. Further
      studies are required to determine whether the prognosis of FIRS caused by intra
      amniotic infection/inflammation is different from that induced by
      alloimmunization.

PMID- 20701436
TI  - Repairing large radial nerve defects by acellular nerve allografts seeded with
      autologous bone marrow stromal cells in a monkey model.
AB  - In this study, we aimed to evaluate the potential of tissue-engineered nerve
      grafts created from acellular allogenic nerve tissues combined with autologous
      bone marrow stromal cells (BMSCs) for repairing large peripheral nerve lesions.
      In a rhesus monkey model, a 2.5-cm-long gap was created in the radial nerve,
      followed by implantation of either autografts or acellular allografts seeded with
      autologous BMSCs, Schwann cells (SCs), or no cells. Five months after surgery
      nerve regeneration was assessed functionally, electrophysiologically, and
      histomorphometrically. Compared to non-cell-laden allografts, BMSC-laden
      allografts remarkably facilitated the recovery of the grasping functions of the
      animals. This functional improvement was coupled with increased nerve conduction
      velocities and peak amplitudes of compound motor action potentials, and greater
      axon growth, as well as higher target muscle weight. Moreover, the intensities of
      nerve regeneration in the BMSC-laden group were comparable to those achieved with
      SC-laden allografts and autografts. Our data highlight the potential of BMSC-seed
      allografts for the repair of long peripheral nerve lesions, and reveal comparable
      regeneration intensities achieved by BMSC-, and SC-laden allografts, as well as
      autografts. Given their wide availability, BMSCs may represent a promising cell
      source for tissue-engineered nerve grafts.

PMID- 20701437
TI  - Today's discoveries to tomorrow's care: cancer biomarkers revisited. Foreword.

PMID- 20701438
TI  - CD24, a promising biomarker in NSCLC.

PMID- 20701439
TI  - From gene to protein expression: improving prognostication of DCIS.

PMID- 20701440
TI  - Emerging biomarkers in breast cancer care.
AB  - Currently, decision-making for breast cancer treatment in the clinical setting is
      mainly based on clinical data, histomorphological features of the tumor tissue
      and a few cancer biomarkers such as steroid hormone receptor status (estrogen and
      progesterone receptors) and oncoprotein HER2 status. Although various therapeutic
      options were introduced into the clinic in recent decades, with the objective of
      improving surgery, radiotherapy, biochemotherapy and chemotherapy, varying
      response of individual patients to certain types of therapy and therapy
      resistance is still a challenge in breast cancer care. Therefore, since breast
      cancer treatment should be based on individual features of the patient and her
      tumor, tailored therapy should be an option by integrating cancer biomarkers to
      define patients at risk and to reliably predict their course of the disease
      and/or response to cancer therapy. Recently, candidate-marker approaches and
      genome-wide transcriptomic and epigenetic screening of different breast cancer
      tissues and bodily fluids resulted in new promising biomarker panels, allowing
      breast cancer prognosis, prediction of therapy response and monitoring of therapy
      efficacy. These biomarkers are now subject of validation in prospective clinical
      trials.

PMID- 20701441
TI  - Personalized medicine in oncology: tailoring the right drug to the right patient.
AB  - Despite advances in the management of many human cancers over the past few
      decades, improvements in survival are marginal, and the overall diagnosis and
      prognosis for cancer patients remain poor. Tailoring therapy to the individual
      patient has become a promising approach for maximizing efficacy and minimizing
      drug toxicity. Aided by major technological advances, the field of personalized
      medicine has become extremely active in the identification of predictive
      biomarkers that can guide treatment decisions and, ultimately, improve treatment
      outcomes. Genomics and proteomics have provided a means for molecular profiling
      that allows tailoring of therapy. Although implementing genomic and proteomic
      testing into clinical practice is still in its infancy, the rapid development of
      newer technologies and platforms provides hope for personalized medicine.

PMID- 20701442
TI  - Use of K-Ras as a predictive biomarker for selecting anti-EGF receptor/pathway
      treatment.
AB  - Ras protein is a downstream regulator of multiple cellular receptor tyrosine
      kinases, mediating cell growth, transformation and maintenance of the malignant
      phenotype in several human cancers. Oncogenic gain-of-function mutations in ras
      frequently occur in colorectal cancer, non-small-cell lung cancer and pancreatic
      cancers. Recent clinical studies of colorectal cancer have revealed that the
      therapeutic efficacy of cetuximab, a chimeric monoclonal antibody against EGF
      receptor, depends on the presence of wild-type k-ras. Additional studies in non
      small-cell lung cancer have suggested that the k-ras mutation may be a negative
      predictor of response to the EGF receptor tyrosine kinase inhibitors erlotinib
      and gefitinib. These observations have provoked an interest in utilizing K-Ras as
      a predictive biomarker, allowing clinicians to direct the therapy of cancer
      patients based on their mutational status of the k-ras gene.

PMID- 20701444
TI  - Is gene expression profiling of head and neck cancers ready for the clinic?
AB  - One of the major challenges in the head and neck oncology clinic is the need to
      identify biomarkers and/or gene expression signatures that complement, strengthen
      and increase the sensitivity and specificity of the current clinicopathologic
      analyses. Microarray analysis of head and neck tumors has demonstrated that the
      combined influence of many genes or biomarkers can make superior identifiers
      and/or predictors of tumor behavior and patient outcome. Here, an update of the
      recent literature on the prognostic and predictive value of microarrays for
      patients with head and neck squamous cell carcinomas is presented. Microarray
      technology has the potential for improved decision-making and corroboration
      within the clinical setting. However, further integration, standardization,
      validation and research are required before the use of microarray analysis is
      ready for routine clinical management of head and neck squamous cell carcinomas.

PMID- 20701445
TI  - Next-generation, genome sequencing-based biomarkers: concerns and challenges for
      medical practice.

PMID- 20701446
TI  - Novel approach for oral cancer biomarker discovery.

PMID- 20701447
TI  - YKL-40: a new biomarker in cardiovascular disease?
AB  - Cardiovascular disease in the form of coronary artery disease is the most common
      cause of death in western countries. Early treatment with stabilizing drugs and
      mechanical revascularization by percutaneous coronary intervention or coronary
      bypass surgery has reduced the mortality significantly. But in spite of improved
      treatments, many patients are still plagued by a high frequency of angina
      symptoms, hospitalizations and a poor prognosis. There is a need for new
      independent or supplementary biomarkers that can help to predict cardiovascular
      disease and cardiovascular events earlier and more precisely, and thus accompany
      existing biomarkers in both primary and secondary cardiovascular prevention. One
      such potential new biomarker is the protein YKL-40. As an independent biomarker
      in both cardiovascular diseases and noncardiovascular diseases, current evidence
      suggests YKL-40 to be most useful as a marker of disease severity, prognosis and
      short survival. However, future studies will evaluate whether YKL-40 can be used
      for monitoring of the treatment effect in different patient populations with a
      distinct disease diagnosis. In this article we explore present knowledge on YKL
      40 as a biomarker in cardiovascular disease.

PMID- 20701448
TI  - An update on markers of carotid atherosclerosis in patients with Type 2 diabetes.
AB  - Carotid atherosclerosis constitutes an important cause of ischemic brain attack
      and stroke, accounting for up to 40% of cases of ischemic cerebrovascular
      disease. Type 2 diabetes mellitus is an independent risk factor for stroke and
      its recurrence. Thus, identifying diabetic patients who are at high risk of
      developing stroke is of great clinical importance. Noninvasive measurements of
      surrogate markers of atherosclerosis, such as novel serum biomarkers, can be
      helpful in detecting subclinical carotid disease, especially among individuals at
      the highest cardio-/cerebro-vascular risk. Previous studies have proposed an
      expanding body of serum biomarkers, such as C-reactive protein, fibrinogen,
      adipokines, cytokines and growth factors, as novel indicators of carotid
      atherosclerosis development that predict carotid-related clinical outcomes.
      Furthermore, those biomarkers are expected to assess the efficacy of both
      pharmaceutical and interventional strategies. Accordingly, it is increasingly
      clear that measuring biomarkers may improve the definition of cerebrovascular
      risk profile in patients with Type 2 diabetes mellitus.

PMID- 20701443
TI  - Epigenomics and ovarian carcinoma.
AB  - Ovarian cancer is the leading cause of death among gynecological cancers. It is
      now recognized that in addition to genetic alterations, epigenetic mechanisms,
      such as DNA methylation, histone modifications and nucleosome remodeling, play an
      important role in the development and progression of ovarian cancer by modulating
      chromatin structure, and gene and miRNA expression. Furthermore, epigenetic
      alterations have been recognized as useful tools for the development of novel
      biomarkers for diagnosis, prognosis, therapeutic prediction and monitoring of
      diseases. Moreover, new epigenetic therapies, such as DNA methyltransferase
      inhibitors and histone deacetylase inhibitors, have been found to be a potential
      therapeutic option, especially when used in combination with other agents. Here
      we discuss current developments in ovarian carcinoma epigenome research, the
      importance of the ovarian carcinoma epigenome for development of diagnostic and
      prognostic biomarkers, and the current epigenetic therapies used in ovarian
      cancer.

PMID- 20701449
TI  - Chromatin conformation signatures: ideal human disease biomarkers?
AB  - Human health is related to information stored in our genetic code, which is
      highly variable even amongst healthy individuals. Gene expression is orchestrated
      by numerous control elements that may be located anywhere in the genome, and can
      regulate distal genes by physically interacting with them. These DNA contacts can
      be mapped with the chromosome conformation capture and related technologies.
      Several studies now demonstrate that gene expression patterns are associated with
      specific chromatin structures, and may therefore correlate with chromatin
      conformation signatures. Here, we present an overview of genome organization and
      its relationship with gene expression. We also summarize how chromatin
      conformation signatures can be identified and discuss why they might represent
      ideal biomarkers of human disease in such genetically diverse populations.

PMID- 20701450
TI  - C-type natriuretic-derived peptides as biomarkers in human disease.
AB  - The natriuretic peptide system comprises three structurally related peptides:
      atrial natriuretic peptide, B-type natriuretic peptide and C-type natriuretic
      peptide. In circulation, they play an important endocrine role in the regulation
      of cardiovascular homeostasis by maintaining blood pressure and extracellular
      fluid volume. Atrial natriuretic peptide and B-type natriuretic peptide have
      gained considerable diagnostic interest as biomarkers in cardiovascular disease.
      By contrast, C-type natriuretic peptide has not yet been ascribed a role in human
      diagnostics. This perspective aims at recapitulating the present biochemical and
      clinical issues concerning C-type natriuretic peptide measurement in plasma as a
      potential biomarker.

PMID- 20701455
TI  - Natural killer cells as indispensable players and therapeutic targets in
      autoimmunity.
AB  - Natural killer (NK) cells of the innate immune system are equipped with a
      cytolytic machinery and produce cytokines, which enable these cells to profoundly
      modify adaptive immune responses to foreign invaders, as well as to self
      antigens. Here we discuss the recent advances in understanding how NK cells can
      proactively influence sequential pathogenic steps that are instrumental for the
      initiation and progression of autoimmune diseases in human and experimental
      disease models. We also discuss the possible use of NK cells as a surrogate
      marker for disease activity and responsiveness to immune therapy. Finally, we
      present results on NK cell-based therapies in inflammatory and autoimmune
      disorders with a focus on existing challenges and current promises for the
      development of more effective therapies.

PMID- 20701454
TI  - Regulatory B cells in autoimmune diseases and mucosal immune homeostasis.
AB  - B lymphocytes contribute to physiological immunity through organogenesis of
      secondary lymphoid organs, presentation of antigen to T cells, production of
      antibodies, and secretion of cytokines. Their role in several autoimmune
      diseases, mainly as producers of pathogenic antibodies, is also well known.
      However, certain subsets of B cells are emerging as the important regulatory cell
      populations in both mouse and human. The regulatory functions of B cells have
      been demonstrated in a variety of mouse models of autoimmune diseases including
      collagen-induced arthritis (CIA), experiment autoimmune encephalomyelitis (EAE),
      anterior chamber-associated immune deviation (ACAID), diabetes, contact
      hypersensitivity (CHS), and intestinal mucosal inflammation. Accumulating
      evidence from both mouse and human studies confirms the existence of regulatory B
      cells, and is beginning to define their mechanisms of action. In this article, we
      first review the history of B cells with regulatory function in autoimmune
      diseases, and summarize the current understanding about the characterizations of
      such B-cell subsets. We then discuss the possible regulatory mechanisms of B
      cells, and specifically define the role of regulatory B cells in immune
      homeostasis in the intestine.

PMID- 20701456
TI  - Could antibodies against serum amyloid A function as physiological regulators in
      humans?
AB  - The natural structuring of the immune system is responsible for the functional
      physiological state of the body. The development of natural autoantibodies
      involved in homeostasis relies on the ability to distinguish between
      exposed/masked and altered/non-altered self antigens. The objectives of this
      article were to address the relationships between antigen and autoantibodies
      against serum amyloid A (SAA), define SAA protein concentrations in 219 blood
      donor (BD) sera and determine their autoantibody levels and search for possible
      clinical associations with autoimmune and thrombotic diseases. Just recently, an
      increasing number of reports have indicated significantly decreased levels of
      autoantibodies against pro-inflammatory molecules, such as anti-TNF-alpha, anti
      IL-6, or anti-CRP found in diseased conditions, as compared to healthy donors, or
      even to less severe disease conditions. In accord with this line of thought, our
      data indicate a predominant presence of anti-SAA autoantibodies in healthy BDs
      (above 95% as tested by the immunoblot analysis, n = 41). Using ELISA, high
      levels of anti-SAA antibodies were confirmed with a median OD = 0.996 for the BD
      group (n = 219). This suggests that anti-SAA antibodies might have a
      physiological role in homeostasis and/or the innate immune system and could
      actually be a part of the natural antibody repertoire. Significantly, lower
      median levels were found in patients with arterial thrombosis. Based on 219 BD
      sera, we could establish a new median value of 20 MUg/ml for SAA antigen and a
      cut-off value of 114.7 MUg/ml (97.5th percentile). Significantly, higher
      concentrations of SAA were observed for antiphospholipid syndrome, rheumatoid
      arthritic, and SLE patients.

PMID- 20701457
TI  - Application of robotic technology in biomechanics to study joint laxity.
AB  - PRIMARY OBJECTIVE: To evaluate whether in vitro joint testing using a robot with
      six degrees of freedom is useful for evaluating changes in joint laxity as a
      result of chronic osteoarthritis (OA). RESEARCH DESIGN: Repeated measures.
      METHODS: Broyden's method of solving nonlinear systems of equations drove a
      hybrid method of load and position robotic control. Sheep stifles (knee joints)
      were loaded between 3 Nm of internal load through to 3 Nm of external load in 1
      Nm increments. Kinematic and morphologic data from five healthy ovine stifles
      were compared to the chronic OA effects in four surgically destabilized stifles.
      RESULTS: Stifles with chronic OA showed increases in stiffness while range of
      motion decreased. Gross morphologic changes included osteophytes and cartilage
      fibrillation. DISCUSSION: Robotic testing proved useful for evaluating changes in
      joint mechanics as a result of chronic OA. We observed morphological changes and
      associated increases in joint stiffness and decreased laxity.

PMID- 20701458
TI  - Soluble CD40 ligand is elevated in type 1 diabetic nephropathy but not predictive
      of mortality, cardiovascular events or kidney function.
AB  - Soluble CD40 ligand (sCD40L) derived from platelets mediates atherothrombosis,
      leading to proinflammatory and proatherosclerotic responses. We investigated the
      predictive value of plasma sCD40L for all-cause mortality, cardiovascular
      mortality and morbidity, progression towards end-stage renal disease (ESRD) and
      rate of decline in glomerular filtration rate (GFR) in patients with type 1
      diabetes (T1DM) and nephropathy. The study was a prospective, observational
      follow-up study of 443 T1DM patients with diabetic nephropathy (274 men; age 42.1
      +/- 10.5 years [mean +/- SD], duration of diabetes 28.3 +/- 8.9 years, GFR 76 +/-
      33 ml/min/1.73 m2) and a control group of 421 patients with longstanding type 1
      diabetes and persistent normoalbuminuria (232 men; age 45.4 +/- 11.5 years,
      duration of diabetes 27.7 +/- 10.1 years) at baseline. sCD40L was measured by
      ELISA. Plasma sCD40L levels were higher in patients with diabetic nephropathy
      compared to normoalbuminuric patients (median (range) 1.54 (0.02-13.38) vs. 1.30
      (0.04-20.65) ug/L, respectively p = 0.004). The patients were followed for 8.1
      (0.0-12.9) years (median (range)). Among normoalbuminuric patients, sCD40L levels
      did not predict all-cause mortality (p = 0.33) or combined fatal and non-fatal
      cardiovascular disease (CVD) (p = 0.27). Similarly, among patients with diabetic
      nephropathy, the covariate adjusted sCD40L levels did not predict all-cause
      mortality (p = 0.86) or risk of fatal and non-fatal CVD (p = 0.08). Furthermore,
      high levels of sCD40L did not predict development of ESRD (p = 0.85) nor rate of
      decline in GFR (p = 0.69). Plasma sCD40L is elevated in T1DM nephropathy but is
      not a predictor of all-cause mortality, cardiovascular mortality and morbidity or
      deterioration of kidney function

PMID- 20701459
TI  - Homocysteine and its thiolactone may promote apoptotic events in blood platelets
      in vitro.
AB  - The actions of homocysteine and its major metabolite, cyclic thioester,
      homocysteine thiolactone on endothelial cells, blood platelets, plasmatic
      fibrinogen and plasminogen--the important major components of haemostasis,
      regulating the flowing properties of blood--are complex and sometimes
      controversial. Homocysteine (Hcys) can promote apoptosis in endothelial cells,
      but the role of Hcys and its thiolactone in the apoptotic process in blood
      platelets is unknown. In order to study the appearance of apoptosis in platelets
      after treatment with the reduced form of Hcys or its thiolactone different
      markers were chosen: annexin V binding (phosphatidylserine exposure), platelet
      microparticle formation, mitochondrial membrane depolarization and alphaIIbbeta3
      expression in vitro. Apoptotic events and platelet activation were measured by a
      flow cytometer. In gel-filtered platelets treated with different concentrations
      of the reduced form of Hcys (25, 50 and 100 uM, 10 min) a significant increase of
      phosphatidylserine exposure (about 37% at the highest concentration, p < 0.001)
      and platelet microparticle formation were observed. Homocysteine caused also a
      dose-dependent depolarization of mitochondrial potential. The same apoptotic
      markers appeared in HTL-treated platelets (0.2 and 1 uM). Moreover, resveratrol
      (25 uM), a well known antioxidant, distinctly reduced the level of apoptotic
      markers. The obtained results indicate that Hcys and its thiolactone may promote
      in vitro apoptotic events in human gel-filtered platelets.

PMID- 20701460
TI  - Use of glycoprotein IIb/IIIa receptor antagonist in prosthetic valve thrombosis.

PMID- 20701461
TI  - The effect of vulvar lichen sclerosus on quality of life and sexual functioning.
AB  - Lichen sclerosus (LS) is a chronic skin disorder mostly seen on the female
      anogenital skin. The aim of this study was to evaluate the quality of life (QoL)
      and sexuality in female patients with LS and to compare their scores with healthy
      controls. In addition, we wanted to find factors associated with impaired sexual
      functioning in patients with LS. Members of the Dutch LS foundation and support
      group were asked to fill in three questionnaires: the Dermatology Quality of Life
      Index, Female Sexual Function Index (FSFI) and Female Sexual Distress Scale
      (FSDS). 215 of 368 patients returned their questionnaire (58.4%). Their scores
      were compared to a control group which consisted of 61 women of similar age (p =
      0.472) without a skin disorder. Of all domains of QoL, LS interfered most with
      sexual functioning. Patients significantly scored lower on all subscales of the
      FSFI (desire (p = 0.016), arousal (p < 0.001), lubrication (p < 0.001), orgasm (p
      < 0.001), satisfaction (p < 0.001) and pain (p < 0.001), indicating worse sexual
      functioning. These problems with sexual functioning brought about significant
      sexual distress (p < 0.001). Patients who experienced more influence on their QoL
      had more sexual difficulties, leading to more sexual distress independent of
      their age.

PMID- 20701462
TI  - Effects of acute electromagnetic field exposure and movement restraint on
      antioxidant system in liver, heart, kidney and plasma of Wistar rats: a
      preliminary report.
AB  - PURPOSE: The aim of the present study was to evaluate the early effects of acute
      (2 h) exposure to extremely low frequency electromagnetic fields (ELF-EMF), as
      well as movement restraint (MR) and the combination of both on the antioxidant
      systems in the plasma, liver, kidney, and heart of rats. MATERIALS AND METHODS:
      Twenty-four adult male Wistar rats were divided in two groups, restrained and
      unrestrained. The restrained animals were confined into an acrylic tube for 120
      min. Half of the animals of each group were exposed to ELF-EMF (60 Hz, 2.4 mT)
      during the period of restriction. Immediately after treatment, reduced
      glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), and thiobarbituric
      acid reactive substances (TBARS) were measured in tissues. RESULTS: GSH
      concentration was significantly lower in the heart of all experimental animals
      when compared to the control group; furthermore, the decrease was higher in the
      liver of restrained animals. SOD activity was lower in the plasma of restrained
      and EMF exposed animals compared to unrestrained rats. There were no significant
      differences in CAT activity and TBARS levels among all the experimental groups
      vs. the control group. CONCLUSION: Two hours of 60 Hz EMF exposure might
      immediately alter the metabolism of free radicals, decreasing SOD activity in
      plasma and GSH content in heart and kidney, but does not induce immediate lipid
      peroxidation. Oxidative stress induced by movement restraint was stronger than
      that produced by EMF.

PMID- 20701464
TI  - Adipose-derived stem cells and BMP2: part 1. BMP2-treated adipose-derived stem
      cells do not improve repair of segmental femoral defects.
AB  - Recombinant human bone morphogenetic protein-2 (rhBMP2) has been shown to induce
      both in vitro osteogenic differentiation and in vivo bone formation, with the
      capacity of rhBMP2 to elicit the repair of numerous bony defects (calvaria,
      spinal fusion, femora, and so on) well documented. In addition, rhBMP2 has been
      approved by the Food and Drug Administration (FDA) for selected human
      indications. Despite the fact that healing is often achieved, the challenge still
      remains to optimize the therapeutic use of rhBMP2. One avenue may be through the
      combination of rhBMP2 with stem cells capable of osteogenic differentiation. This
      study investigates the ability of rhBMP2 at various doses in combination with
      human adipose-derived stem cells (ASCs) to heal critical-sized rat segmental
      femoral defects. For this, different doses of rhBMP2 were incorporated with
      apatite-coated porous poly(l-lactide-co-dl-lactide) (70  :  30) (PLDLA)
      scaffolds, seeded with ASCs, and implanted into athymic rats. After 8 weeks, all
      implants were harvested and processed for bone formation using micro computed
      tomography (microCT) analysis and histology. Despite the findings that indicate
      no adverse effect of the apatite surface on ASC osteogenesis, no significant
      difference in bone formation could be qualitatively or quantitatively determined
      upon the implantation of ASC-seeded scaffolds absorbed to increasing doses of
      rhBMP2. Such results would suggest that the presence of ASCs within rhBMP2
      absorbed scaffolds does not improve the bone-forming ability of the construct and
      that the formation of bone may be driven by the rhBMP2 alone. Based on these
      results, the addition of ASCs to rhBMP2-treated scaffolds may provide no
      significant advantage in terms of the ability to heal bone.

PMID- 20701465
TI  - Adipose-derived stem cells and BMP2: part 2. BMP2 may not influence the
      osteogenic fate of human adipose-derived stem cells.
AB  - Although recent studies have proposed that human adipose-derived stem cells
      (ASCs), together with BMP2, can heal critical-sized bony defects, a companion
      study in this issue suggests that ASCs may not respond to BMP2 in vivo. To
      examine why this may be occurring. ASCs were treated with BMP2 and the cells' in
      vitro osteogenic capacity assessed along with the canonical BMP2 signaling
      pathway. In vitro treatment of ASCs with BMP2 had no consistent and significant
      effect on matrix mineralization or their expression of several osteogenic
      markers. Consistent and significant changes to Smad1/5/8 phosphorylation levels
      were also not observed upon BMP2 induction. The removal of dexamethasone from the
      BMP2 induction conditions had no effect on the observed results nor did
      stimulating ASCs with BMP2 from an alternate source (INFUSE; Medtronic,
      Minneapolis, MN, USA). In addition, no BMP-induced nuclear translocation of
      Smad1/Smad4 complexes could be discerned, suggesting that the canonical BMP2
      signaling pathway may not be functional in ASCs. Interestingly, three downstream
      BMP2 pathway genes, distal-less3 (dlx3), distal-less5 (dlx5), and osterix, were
      not expressed in BMP2-induced ASCs, calling the utility of BMP2 induced in ASCs
      into question. The results of this in vitro study were consistent with that of
      our companion in vivo study that suggests a lack of effect of BMP2 on the
      osteogenic capacity of ASCs. Taken together, the data from both studies suggest
      that ASC osteogenic differentiation may not be influenced by BMP2. Consequently,
      combining BMP2 treatment with adult stem cells, like ASCs, may not be a viable
      strategy for bony healing.

PMID- 20701466
TI  - EMILIN-1 regulates the amount of oxytalan fiber formation in periodontal
      ligaments in vitro.
AB  - The elastic system fibers comprise oxytalan, elaunin, and elastic fibers,
      differing in their relative microfibril and elastin contents. Among them, human
      periodontal ligament (PDL) contains only oxytalan fibers (pure microfibrils).
      Elastin microfibril interface-located protein-1 (EMILIN-1) is localized at the
      interface between microfibrils and elastin. We hypothesized that EMILIN-1 may
      contribute to the formation of oxytalan fibers. We used a small interfering RNA
      (siRNA) for EMILIN-1 in PDL cell culture to examine the extracellular deposition
      of fibrillin-1 (the major component of microfibrils). EMILIN-1 was labeled on
      microfibrils positive for fibrillin-1 and was colocalized with fibrillin-1 upon
      immunoprecipitation assay. EMILIN-1 suppression reduced the level of fibrillin-1
      deposition to 23% of the control, and this was responsible for the diminution of
      fibrillin-1 deposition revealed by immunofluorescence. These results suggest that
      EMILIN-1 may regulate the formation of oxytalan fibers and play a role in their
      homeostasis.

PMID- 20701467
TI  - Are early and late preeclampsia distinct subclasses of the disease--what does the
      placenta reveal?
AB  - OBJECTIVE: To compare histopathological differences in placentas from early- and
      late-onset preeclampsia, as well as late-onset preeclampsia and normal term
      deliveries. METHODS: This prospective study was performed at Tygerberg Hospital,
      a secondary and tertiary referral center in South Africa. Placentas from 100
      women, 25 each with early and late-onset preeclampsia, and an equal number of
      controls matched for gestational age, underwent routine preparation and were
      evaluated independently by two pathologists in a strictly predetermined,
      standardized manner. RESULTS: Compared to late preeclampsia, placentas in the
      early preeclampsia group were smaller (p < 0.01), had more infarction (odds ratio
      [OR] = 4.03, 95% confidence interval [CI] = 1.2-13.5) and inappropriate
      maturation (OR = 16.62, 95% CI = 4.1-68.0). Placentas from the late-onset
      preeclampsia group showed increased decidual arteriopathy (OR = 5.09, 95% CI =
      1.45-17.92) and abruptio placentae (OR = 5.41, 95% CI = 1.01-28.79) compared to
      controls. CONCLUSIONS: The early- and late-onset preeclampsia placentas showed
      clear histopathological differences, whereas late-onset preeclampsia and normal
      term placentas differed less. These findings support the contention that early-
      and late-onset preeclampsia are different subclasses of disease.

PMID- 20701469
TI  - Assessment of genetic contributions to risk of preeclampsia in Ecuadorian women.
AB  - AIM: To identify the immunogenetic factors that trigger the beginning of
      preeclampsia and eclampsia. METHODS: A retrospective, case-control study of 142
      pregnant women in Obstetrics and Gynecological Hospital Isidro Ayora in Quito,
      who are grouped into two different groups, diseased and healthy. The study
      analyzed ethnicity, age, gynecological history, contraception, immunizations,
      blood type and Rh factor, and family history of preeclampsia-eclampsia of each of
      the pregnant women; and gestational age, sex, weight, and blood type and Rh
      factor of the progeny. RESULTS: Age, ethnicity, history of pregnancy, abortions,
      contraception, and blood type and Rh factor were similar for both groups (p >
      0.05). Gestational age and weight of the progeny was lower in cases compared with
      controls (p < 0.05). There was no statistical difference when comparing the blood
      type and Rh factor of the two groups (p > 0.05). Male gender was predominant in
      both groups for cases 69.01 and 87.32% for controls (p < 0.05). CONCLUSIONS:
      There was a higher predisposition for inherited cases (26%) versus controls
      (9.85%), p < 0.05, for the occurrence of preeclampsia. The frequency of the
      recessive gene for Mendelian inheritance model mother-fetus homozygous (aa/aa),
      in agreement with the Hardy-Weinberg Law, was 0.41 for the sample.

PMID- 20701468
TI  - Does C-reactive protein predict recurrent preeclampsia?
AB  - OBJECTIVE: Evaluate association of the inflammatory marker C-reactive protein
      with recurrent preeclampsia. METHODS: Serum samples collected longitudinally in
      women with previous preeclampsia from the Maternal-Fetal Medicine Units Network
      trial of aspirin to prevent preeclampsia were assayed for CRP. RESULTS: Of 255
      women studied, 50 developed recurrence. Baseline C-reactive protein concentration
      was similar between women who did and did not recur. After adjusting for
      confounders, neither elevated baseline C-reactive protein nor its change over
      gestation was associated with recurrence. CONCLUSION: In this group of women with
      previous preeclampsia, neither baseline C-reactive protein concentration nor
      change in concentration over gestation was associated with recurrent
      preeclampsia.

PMID- 20701470
TI  - Amino-terminal pro-brain natriuretic peptide levels in hypertensive disorders
      complicating pregnancy.
AB  - OBJECTIVE: Amino-terminal pro-brain natriuretic peptide (NT-proBNP) is
      synthesized in cardiac ventricles in response to volume expansion. This study
      evaluated NT-proBNP levels to determine the clinical correlation with the
      severity of hypertensive disorders complicating pregnancy. METHODS: NT-proBNP
      levels of 95 pregnant women (severe preeclampsia [n = 26], mild preeclampsia [n =
      15], gestational hypertension [n = 9], and healthy controls [n = 45]) were
      determined using an electrochemiluminescence immunoassay. RESULTS: Comparisons of
      the mean values of NT-proBNP levels in the different groups were significantly
      different, as follows: 1766.43 +/- 4197.39 pg/mL (median, 339.8 pg/mL) in severe
      preeclampsia, 214.97 +/- 226.35 pg/mL (median, 152.3 pg/mL) in mild preeclampsia,
      39.75 +/- 24.85 pg/mL (median, 34.09 pg/mL) in gestational hypertension, and
      78.78 +/- 81.56 pg/mL (median, 48.54 pg/mL) in the healthy controls. The NT
      proBNP levels of the patients with mild and severe preeclampsia were
      significantly higher than in the patients with gestational hypertension and the
      healthy control patients. There was no significant difference in NT-proBNP levels
      between patients with mild and severe preeclampsia (p = 0.17). CONCLUSION: In
      patients with mild and severe preeclampsia, NT-proBNP levels were elevated. This
      may reflect ventricular stress and/or subclinical cardiac dysfunction associated
      with preeclampsia.

PMID- 20701471
TI  - Are insulin resistance index, IGF-1 and metabolic syndrome components correlates
      with severe preeclampsia?
AB  - OBJECTIVE: Analyse the relation between insulin resistance and severe
      preeclampsia (SPE). METHODS: Case control study paired by body mass index and
      gestational age; including 16 patients with severe SPE and 16 normotensive
      controls. Insulin resistance was assessed through the HOMA-IR and QUICKI-IS
      indexes. RESULTS: There was no significant difference between the groups
      regarding the HOMA-IR and QUICKI-IS indexes and HDL cholesterol. Triglyceride
      levels were higher and the IGF-1 was lower in the SPE group than in the control
      group. CONCLUSIONS: There were no differences in the insulin resitance indexes
      between the group with SPE and normal controls.

PMID- 20701472
TI  - Placental protein-13 and pregnancy-associated plasma protein-A as first trimester
      screening markers for hypertensive disorders and small for gestational age
      outcomes.
AB  - OBJECTIVE: To investigate the role of placenta protein 13 (PP13) and pregnancy
      associated plasma protein-A (PAPP-A) in hypertensive disorders and small for
      gestational age (SGA) during first trimester of pregnancy. METHODS: In this case
      control study, first trimester serum samples (11(+0) to 13(+6) weeks) were
      retrieved from frozen storage of which 452 were from normal pregnancies and 47
      samples were identified to have pregnancies with at least one of the following
      adverse outcomes: SGA, preeclampsia (PE), hemolysis, elevated liver enzymes, and
      low platelets (HELLP), or gestational hypertension (GH). PP13 concentrations were
      measured by a new AutoDELFIA method. Levels of PAPP-A were measured for a first
      trimester screening program using Kryptor analyzer. RESULTS: First trimester
      levels of PAPP-A are significantly lower in cases of SGA, PE, and most subgroups
      including HELLP. Levels of PP13 were not found to differ between control and
      affected pregnancies. CONCLUSION: PP13 needs to be studied further as our results
      contrast the majority of previous studies.

PMID- 20701473
TI  - Lupus nephritis mimicking pyelonephritis in pregnancy.
AB  - BACKGROUND: Systemic lupus erythematosis (SLE) is a multisystemic autoimmune
      connective tissue disorder that presents with a wide range of clinical
      manifestations including renal involvement. Routine prenatal care includes
      assessment of renal function. CASE: A 29-year-old nullipara presented at 17 weeks
      with fever, vomiting, and costovertebral angle tenderness 1 week after being
      treated for a presumed urinary tract infection. On presentation, new-onset
      hypertension was noted. Inpatient evaluation established a diagnosis of SLE with
      lupus nephritis. The pregnancy ended with intrauterine fetal demise. CONCLUSION:
      SLE is a disease with complex and protean clinical manifestations. It should
      appear on the differential when more common disease processes are ruled out.
      Routine prenatal care can detect otherwise silent and undiagnosed renal disease,
      and with early intervention improve prognosis.

PMID- 20701474
TI  - Postpartum hyperkalemia associated with magnesium sulfate.
AB  - We report the case of a woman who first received MgSO(4) for eclampsia
      prophylaxis and then was treated with MgSO(4) for eclampsia. She developed
      hyperkalemia without severe renal failure or another explanation. We recommend
      close monitoring, including serial measurements of electrolytes, when MgSO(4) is
      administered for eclampsia prophylaxis or treatment.

PMID- 20701475
TI  - The biological investigation of prostacyclin in preeclamptic women seen reduced
      endothelial function.
AB  - OBJECTIVE: Our aim was to determine the biological investigation of prostacyclin
      in preeclamptic women seen reduced endothelial vasodilatation by non-invasive
      technique in vivo. METHODS: Using a high resolution ultrasound transducer,
      diameters of brachial arteries were determined after reactive hyperemia in 15 non
      pregnant, 20 normotensive pregnant and 20 preeclamptic women. The concentrations
      of 6-keto-prostaglandin F 1alpha (6keto-PGF 1alpha) in plasma and the
      concentrations of adenosine-3', 5'-cyclic monophosphate (cyclic AMP) in platelets
      and serum were measured among the groups. RESULTS: Flow-mediated vasodilatation
      at 1 min after reactive hyperemia was higher in normotensive pregnant than in the
      non-pregnant or preeclamptic women. The plasma concentration of 6 keto-PGF 1alpha
      as well as the serum concentration of cyclic AMP were lower in preeclamptic than
      those in normotensive pregnant women. The increase in cyclic AMP in the presence
      of a prostacyclin analogue in platelets was seen at similar levels in all three
      groups. CONCLUSION: From these results, the concentrations of prostacyclin in
      plasma and cyclic AMP in serum might be low possibly due to reduced production of
      prostacyclin in preeclamptic women seen reduced endothelial function.

PMID- 20701476
TI  - Increased risk of hypertension, proteinuria and preeclampsia in pregnant Saudi
      females with IgA nephropathy.
AB  - BACKGROUND: IgA nephropathy is fairly prevalent in Saudi Arabia. In this paper we
      examine the natural history of pregnancies and their impact on renal function in
      Saudi females affected by this condition. METHODS: We followed a series of 12
      patients, documented to have IgA nephritis by kidney biopsy, during their
      gestation. We monitored their blood pressure, serum creatinine, creatinine
      clearance, 24-hour protein before conception and at the third trimester of
      pregnancy. We also documented any maternal or fetal complications. RESULTS: All
      patients had well-controlled blood pressure, normal renal function, and
      proteinuria of less than one gram per day prior to conception. During pregnancy,
      all patients (100%) developed hypertension-requiring treatment and three of them
      (25%) developed preeclampsia. One patient (8.3%) had hemolysis, elevated liver
      enzymes, and, low platelets syndrome. All patients had worsening of their
      proteinuria during pregnancy from 535.2 (101.4) to 2179.2 (636.6) mg/24 h (p <
      0.01) with a decrease in creatinine clearance from 88.6 (7.6) mls/min to 77.4
      (5.9) mls/min (p < 0.05). No fetal complications were observed. CONCLUSION: We
      conclude that pregnancies in patients, even with mild IgA nephritis, require
      close observation as there is an increased incidence of worsening hypertension
      and preeclampsia.

PMID- 20701477
TI  - Urinary inositol phosphoglycan P-type as a marker for prediction of preeclampsia
      and novel implications for the pathophysiology of this disorder.
AB  - OBJECTIVE: Hypertensive disorders represent the most common complications of
      human pregnancy with substantial impact on fetal and maternal outcomes. Inositol
      phosphoglycan P-type has recently been identified as a novel marker of
      preeclampsia, the most severe form of hypertension during pregnancy, with a
      significant increase in urinary excretion preceding the clinical diagnosis.
      METHODS: A prospective, longitudinal study was carried out to assess the
      potential of urinary levels of inositol phosphoglycan P-type as a screening test
      for preeclampsia. A specific ELISA-based test was used to assess urinary levels
      of P-IPG. RESULTS: Nine patients out of 93 women recruited (496 urinary samples
      were collected) went on to develop preeclampsia in a cohort of women with high
      risk pregnancies. A cut-off value of urinary inositol phosphoglycan P-type was
      identified by ROC analysis providing a sensitivity and specificity for the
      current protocol of 88.9% and 62.7%, respectively. Twenty-three women with
      healthy pregnancies had sporadic episodes of increased excretion of inositol
      phosphoglycan P-type during pregnancy that consistently resolved back to normal
      baseline without development of preeclampsia. There was no correlation of urine
      levels of inositol phosphoglycan P-type and urine protein and patients with
      gestational hypertension had normal levels of urine inositol phosphoglycan P
      type. CONCLUSIONS: These findings suggest that, given the rapid raise of P-IPG
      before the onset of the disease, multiple assessments may help at identifying
      women at risk of developing preeclampsia.

PMID- 20701478
TI  - Skin autofluorescence as marker of tissue advanced glycation end-products
      accumulation in formerly preeclamptic women.
AB  - CONDENSATION: In women with a history of preeclampsia skin autofluorescence as
      marker of tissue AGEs accumulation is increased, supporting a common causal
      metabolic or vascular link between preeclampsia and cardiovascular diseases.
      OBJECTIVE: To investigate whether skin autofluorescence (AF), as marker of tissue
      accumulation of advanced glycation end-products (AGEs), is elevated in women with
      a 4-year history of severe preeclampsia. METHODS: About 17 formerly preeclamptic
      women and 16 controls were included. Skin AF and several traditional
      cardiovascular risk factors were recorded. RESULTS: In comparison to controls,
      formerly preeclamptic women had higher skin AF of the legs, body mass index
      (BMI), blood pressure, and high-sensitivity C-reactive protein (hsCRP), HbA1C,
      and triglycerides in serum. CONCLUSION: Skin AF as well as cardiovascular risk
      factors is elevated in formerly preeclamptic women. These results suggest a
      common causal vascular link between preeclampsia and cardiovascular diseases.

PMID- 20701479
TI  - A randomized pilot study of acupuncture as an adjunct therapy in adult asthmatic
      patients.
AB  - OBJECTIVE: This trial aimed to evaluate the feasibility of estimating the
      effectiveness of acupuncture on asthmatic patients under conventional medical
      management. PARTICIPATIONS AND METHODS: A prospective randomized,
      patient/assessor-blinded, sham acupuncture-, and waiting list-controlled pilot
      trial was conducted. Forty-five eligible asthmatic participants underwent a 1
      week run-in period and were then randomized into one of three groups: an active
      acupuncture group, a sham acupuncture group, and a waiting list group. They were
      instructed to maintain the use of antiasthmatic medications. Needling was
      administered three times per week for 4 weeks with a 2-week follow-up in the
      active and sham acupuncture groups. The primary outcome was daily morning peak
      expiratory flow (PEF) and the secondary outcomes included forced expiratory
      volume one second (FEV(1)), quality of life questionnaire for adult Korean
      asthmatics (QLQAKA), transition dyspnea index (TDI), serum eosinophil count, and
      total serum immunoglobulin E (IgE). RESULTS: No significant differences in the
      between- or within-group values of weekly average PEF (recorded daily in the
      morning) and FEV(1) were found. For QLQAKA and TDI, the active acupuncture group
      showed a significant improvement over the waiting list group at 2, 4, and 6 weeks
      after randomization. DISCUSSION: Acupuncture as an adjunct therapy to
      conventional medical care does not seem to affect pulmonary function in asthmatic
      patients. However, 12 sessions of acupuncture treatment during 4 weeks showed a
      favorable effect on the quality of life in adult asthmatic patients. Further
      large trials assessing the effectiveness of acupuncture on the quality of life
      and symptoms in asthmatic patients are needed.

PMID- 20701480
TI  - Inhibitory effects of antioxidant reagent in reactive oxygen species generation
      and penetration of appressoria of Alternaria alternata Japanese pear pathotype.
AB  - In the Japanese pear pathotype of Alternaria alternata, H2O2 is generated solely
      from penetration pegs and not from other portions of subcuticular hyphae within
      the pectin layers of host leaves. A close association between H2O2 generation and
      fungal aggressiveness is expected because the pegs are important for fungal
      penetration into the host epidermis. To determine the potential role of reactive
      oxygen species in microbial pathogenicity, we studied the inhibitory effects of
      the antioxidant reagent ascorbic acid and the NADPH oxidase inhibitor diphenylene
      iodonium on infection of the pathogen. In our study, we showed H2O2 generation to
      be inhibited by inoculation with the mixture of ascorbic acid or diphenylene
      iodonium and spores at the pegs in the spore-inoculated host leaves. The decrease
      of generation in the pegs resulted in penetration failure, indicating that H2O2
      generation probably contributed to strengthening of the penetration and probably
      was recruited by NADPH oxidase.

PMID- 20701482
TI  - Sexual recombinants make a significant contribution to epidemics caused by the
      wheat pathogen Phaeosphaeria nodorum.
AB  - We conducted a 2-year mark-release-recapture field experiment to quantify the
      relative contributions of immigration and sexual and asexual reproduction to
      epidemics of Stagonospora nodorum blotch caused by Phaeosphaeria nodorum. The
      epidemic was initiated using nine genetically distinct P. nodorum isolates.
      Infected plants were sampled four times across two growing seasons. In total,
      1,286 isolates were recovered and assayed with 10 microsatellite markers and 1
      minisatellite marker. The proportion of isolates having multilocus haplotypes
      (MLHTs) identical to the inoculated isolates decreased steadily from 86% in the
      first collection to 25% in the fourth collection. The novel isolates that had
      different MLHTs compared with the marked inoculants originated through
      immigration and sexual recombination. By the end of the experiment, nearly three
      quarters of the novel isolates originated from sexual recombination. Our results
      indicate that recombinant offspring and airborne immigrant ascospores can make
      significant contributions to epidemics of Stagonospora nodorum blotch during a
      growing season.

PMID- 20701481
TI  - Mass spectrometric analysis reveals remnants of host-pathogen molecular
      interactions at the starch granule surface in wheat endosperm.
AB  - The starch granules of wheat seed are solar energy-driven deposits of fixed
      carbon and, as such, present themselves as targets of pathogen attack. The seed's
      array of antimicrobial proteins, peptides, and small molecules comprises a
      molecular defense against penetrating pathogens. In turn, pathogens exhibit an
      arsenal of enzymes to facilitate the degradation of the host's endosperm. In this
      context, the starch granule surface is a relatively unexplored domain in which
      unique molecular barriers may be deployed to defend against and inhibit the late
      stages of infection. Therefore, it was compelling to explore the starch granule
      surface in mature wheat seed, which revealed evidence of host-pathogen molecular
      interactions that may have occurred during grain development. In this study,
      starch granules from the soft wheat Triticum aestivum cv. AC Andrew and hard
      wheat T. turgidum durum were isolated and water washed 20 times, and their
      surface proteins were digested in situ with trypsin. The peptides liberated into
      the supernatant and the peptides remaining at the starch granule surface were
      separately examined. In this way, we demonstrated that the identified proteins
      have a strong affinity for the starch granule surface. Proteins with known
      antimicrobial activity were identified, as well as several proteins from the
      plant pathogens Agrobacterium tumefaciens, Pectobacterium carotovorum, Fusarium
      graminearum, Magnaporthe grisea, Xanthomonas axonopodis, and X. oryzae. Although
      most of these peptides corresponded to uncharacterized hypothetical proteins of
      fungal pathogens, several peptide fragments were identical to cytosolic and
      membrane proteins of specific microbial pathogens. During development and
      maturation, wheat seed appeared to have resisted infection and lysed the
      pathogens where, upon desiccation, the molecular evidence remained fixed at the
      starch granule surface.

PMID- 20701483
TI  - Multiple infection of apple trees by distinct strains of 'Candidatus Phytoplasma
      mali' and its pathological relevance.
AB  - Forty-eight apple trees infected by 'Candidatus Phytoplasma mali' were examined
      using single-strand conformation polymorphism (SSCP) and sequence analysis of a
      variable hflB gene fragment and the immunodominant membrane protein-encoding imp
      gene. SSCP analysis of polymerase chain reaction-amplified hflB gene fragments
      revealed diverse profiles, differing in number and position of the bands. The
      'Ca. P. mali' content of a single infected apple tree was termed an accession.
      Cloning of fragments from accessions that yielded fewer bands resulted in clone
      populations showing uniform or moderately polymorphic SSCP patterns and largely
      homogenous nucleotide sequences. In contrast, inserts from accessions yielding
      more bands were heterogeneous and formed two to four distinct groups of profiles.
      DNA fragments from such accessions were diverse and clustered distantly when
      subjected to phylogenetic analysis, mostly as two homogenous groups plus one or a
      few other sequences. Similar results were obtained upon imp gene examination. The
      collective data indicate that accessions exhibiting more complex patterns were
      composed of two or three distinct 'Ca. P. mali' strains. There is evidence that
      multiple infections are of pathological relevance due to strain interactions
      leading to shifts in the populations. In triply infected trees of one accession,
      no specific symptoms were induced by the presence of two of the strains. The rare
      appearance of pronounced symptoms was associated with a separate strain that
      possessed a unique SSCP profile and a unique hflB sequence. The two mild strains
      from this apple accession also induced only mild symptoms on periwinkle and
      tobacco and occurred specifically in one of these plants.

PMID- 20701484
TI  - Abscisic acid in salt stress predisposition to phytophthora root and crown rot in
      tomato and chrysanthemum.
AB  - Plants respond to changes in the environment with complex signaling networks,
      often under control of phytohormones that generate positive and negative
      crosstalk among downstream effectors of the response. Accordingly, brief
      dehydration stresses such as salinity and water deficit, which induce a rapid and
      transient systemic increase in levels of abscisic acid (ABA), can influence
      disease response pathways. ABA has been associated with susceptibility of plants
      to bacteria, fungi, and oomycetes but relatively little attention has been
      directed at its role in abiotic stress predisposition to root pathogens. This
      study examines the impact of brief salinity stress on infection of tomato and
      chrysanthemum roots by Phytophthora spp. Roots of plants in hydroponic culture
      exposed to a brief episode of salt (sodium chloride) stress prior to or after
      inoculation were severely diseased relative to nonstressed plants. Tomato roots
      remained in a predisposed state up to 24 h following removal from the stress. An
      increase in root ABA levels in tomato preceded or temporally paralleled the onset
      of stress-induced susceptibility, with levels declining in roots prior to
      recovery from the predisposed state. Exogenous ABA could substitute for salt
      stress and significantly enhanced pathogen colonization and disease development.
      ABA-deficient tomato mutants lacked the predisposition response, which could be
      restored by complementation of the mutant with exogenous ABA. In contrast,
      ethylene, which exacerbates disease symptoms in some host-parasite interactions,
      did not appear to contribute to the predisposition response. Thus, several lines
      of evidence support ABA as a critical and dominant factor in the salinity-induced
      predisposition to Phytophthora spp. infection.

PMID- 20701485
TI  - Characterization of a novel broad-spectrum antifungal protein from virus-infected
      Helminthosporium (Cochliobolus) victoriae.
AB  - A broad-spectrum anti-fungal protein of approximately 10 kDa, designated
      victoriocin, was purified from culture filtrates of a virus-infected isolate of
      the plant-pathogenic fungus Helminthosporium victoriae (teleomorph: Cochliobolus
      victoriae) by a multistep procedure involving ultrafiltration and reverse-phase
      high-performance liquid chromatography (RP-HPLC). Amino acid sequences, obtained
      by automated Edman degradation sequencing of RP-HPLC-purified victoriocin-derived
      peptides, were used to design primers for degenerate oligonucleotide-primed
      polymerase chain reaction (DOP-PCR) amplification from H. victoriae DNA and cDNA
      templates. An open reading frame coding for a victoriocin precursor of 183 amino
      acids with calculated molecular mass of approximately 20 kDa was amplified by PCR
      from H. victoriae genomic DNA but not from the control fungus Penicillium
      chrysogenum. Southern hybridization analysis confirmed the presence of the
      victoriocin gene in all H. victoriae strains tested. Sequence analysis indicated
      that victoriocin has a sequence motif similar to that found in scorpion short
      toxin/charybdotoxin and a consensus sequence similar to that found in defensins.
      Victoriocin, like some other antifungal proteins, including the totivirus-encoded
      killer proteins, is predicted to be expressed in vivo as a preprotoxin precursor
      consisting of a hydrophobic N-terminal secretion signal followed by a pro-region
      and terminating in a classical Kex2p endopeptidase cleavage site that generates
      the N terminus of the mature victoriocin. A putative cell wall protein of
      approximately 30 kDa (P30) co-purified with victoriocin from cultural filtrates.
      The potential role of P30 in the antifungal activity of H. victoriae culture
      filtrates is discussed.

PMID- 20701486
TI  - Overexpression of the victoriocin gene in Helminthosporium (Cochliobolus)
      victoriae enhances the antifungal activity of culture filtrates.
AB  - We have previously reported the isolation and characterization of the broad
      spectrum antifungal protein, victoriocin, from culture filtrates of a virus
      infected isolate of the plant-pathogenic fungus Helminthosporium (teleomorph:
      Cochliobolus) victoriae. We predicted that the 10-kDa mature victoriocin is
      derived in vivo from a preprotoxin precursor that is processed by a signal
      peptidase and kexin-like endopeptidase. We also presented evidence that the
      victoriocin precursor is encoded by a host gene, designated the victoriocin (vin)
      gene. In the present study, an H. victoriae genomic DNA library was constructed
      in the cosmid vector pMLF-2, and a cosmid clone carrying the vin gene and
      flanking sequences was isolated and used to generate constructs for
      transformation of virus-free and virus-infected H. victoriae isolates with the
      vin gene. Culture filtrates of the virus-free vin transformants exhibited high
      levels of antifungal activity compared with that revealed by the nontransformed
      virus-free wild-type strain, which exhibited little or no antifungal activity.
      Moreover, transformation of the wild-type virus-infected H. victoriae strain with
      the vin gene resulted in still higher production of victoriocin and higher
      antifungal activity in the culture filtrates of the vin transformants compared
      with the virus-infected wild-type strain. As previously predicted, the presence
      in the vin transformants of the preprovictoriocin and its post-translationally
      generated products, the provictoriocin and the mature victoriocin, was clearly
      demonstrated. Processing of the victoriocin preprotoxin requires eukaryotic host
      factors because no processing occurred in an in vitro translation system or in
      bacteria. It is of interest that some of the virus-free isolates transformed with
      the vin gene exhibited some features of the virus-induced disease phenotype,
      including moderate stunting and sectoring. Present data suggests that victoriocin
      may play an indirect role in disease development. Taken together, these results
      indicate that victoriocin is the primary protein responsible for the antifungal
      activity in culture filtrates of virus-infected H. victoriae isolates and that
      virus infection upregulates the expression of victoriocin. Overproduction of
      victoriocin may give the slower-growing virus-infected fungal strains some
      competitive advantage by inhibiting the growth of other fungi.

PMID- 20701487
TI  - Response of soybean pathogens to glyceollin.
AB  - Plants recognize invading pathogens and respond biochemically to prevent invasion
      or inhibit colonization in plant cells. Enhancing this response in crop plants
      could improve sustainable methods to manage plant diseases. To enhance disease
      resistance in soybean, the soybean phytoalexin glyceollin was assessed in soybean
      hairy roots of two soybean genotypes, Spencer and PI 567374, transformed with
      either soybean isoflavone synthase (IFS2) or chalcone synthase (CHS6) genes that
      were inoculated with the soybean pathogens Diaporthe phaseolorum var.
      meridionales, Macrophomina phaseolina, Sclerotinia sclerotiorum, and Phytophthora
      sojae. The hairy-root-transformed lines had several-fold decreased levels of
      isoflavone daidzein, the precursor of glyceollin, and considerably lower
      concentrations of glyceollin induced by pathogens measured 5 days after fungal
      inoculation compared with the nontransformed controls without phenolic
      transgenes. M. phaseolina, P. sojae, and S. sclerotiorum grew much more on IFS2-
      and CHS6-transformed roots than on control roots, although there was no
      significant difference in growth of D. phaseolorum var. meridionales on the
      transformed hairy-root lines. In addition, glyceollin concentration was lower in
      D. phaseolorum var. meridionales-inoculated transformed and control roots than
      roots inoculated with the other pathogens. Glyceollin inhibited the growth of D.
      phaseolorum var. meridionales, M. phaseolina, P. sojae, S. sclerotiorum, and
      three additional soybean pathogens: Cercospora sojina, Phialophora gregata, and
      Rhizoctonia solani. The most common product of glyceollin conversion or
      degradation by the pathogens, with the exception of P. sojae, which had no
      glyceollin degradation products found in the culture medium, was 7
      hydroxyglyceollin.

PMID- 20701488
TI  - Variation and transgression of aggressiveness among two Gibberella zeae crosses
      developed from highly aggressive parental isolates.
AB  - Gibberella zeae (anamorph: Fusarium graminearum) is the most common cause of
      Fusarium head blight (FHB) of wheat (Triticum aestivum) worldwide. Aggressiveness
      is the most important fungal trait affecting disease severity and stability of
      host resistance. Objectives were to analyze in two field experiments (i)
      segregation for aggressiveness among 120 progenies from each of two crosses of
      highly aggressive parents and (ii) stability of FHB resistance of seven
      moderately to highly resistant winter wheat cultivars against isolates varying
      for aggressiveness. Aggressiveness was measured as FHB severity per plot,
      Fusarium exoantigen absorbance, and deoxynivalenol content. In the first
      experiment, mean FHB ratings were 20 to 49% across environments and progeny.
      Significant genotypic variation was detected in both crosses (P < 0.01). Isolate
      environment interaction explained approximately half of the total variance. Two
      transgressive segregants were found in cross B across environments. Traits were
      significantly (P < 0.05) intercorrelated. In the second experiment, despite
      significant (P < 0.05) genotypic variance for cultivar and isolate, no
      significant (P > 0.05) interaction was observed for any trait. In conclusion,
      progeny of highly aggressive parents might exhibit increased aggressiveness due
      to recombination and may, therefore, adapt nonspecifically to increased
      quantitative host resistance.

PMID- 20701489
TI  - Induction of systemic resistance in plants by biochar, a soil-applied carbon
      sequestering agent.
AB  - Biochar is the solid coproduct of biomass pyrolysis, a technique used for carbon
      negative production of second-generation biofuels. The biochar can be applied as
      a soil amendment, where it permanently sequesters carbon from the atmosphere as
      well as improves soil tilth, nutrient retention, and crop productivity. In
      addition to its other benefits in soil, we found that soil-applied biochar
      induces systemic resistance to the foliar fungal pathogens Botrytis cinerea (gray
      mold) and Leveillula taurica (powdery mildew) on pepper and tomato and to the
      broad mite pest (Polyphagotarsonemus latus Banks) on pepper. Levels of 1 to 5%
      biochar in a soil and a coconut fiber-tuff potting medium were found to be
      significantly effective at suppressing both diseases in leaves of different ages.
      In long-term tests (105 days), pepper powdery mildew was significantly less
      severe in the biochar-treated plants than in the plants from the unamended
      controls although, during the final 25 days, the rate of disease development in
      the treatments and controls was similar. Possible biochar-related elicitors of
      systemic induced resistance are discussed.

PMID- 20701490
TI  - Extending the fungal host range of a partitivirus and a mycoreovirus from
      Rosellinia necatrix by inoculation of protoplasts with virus particles.
AB  - The potential host range of mycoviruses is poorly understood because of the lack
      of suitable inoculation methods. Recently, successful transfection has been
      reported for somatically incompatible fungal isolates with purified virus
      particles of two mycoviruses, the partitivirus RnPV1-W8 (RnPV1) and the
      mycoreovirus RnMyRV3/W370 (MyRV3), from the white root rot fungus Rosellinia
      necatrix (class Sordariomycetes, subclass Xylariomycetidae). These studies
      examined and revealed the effect of the mycoviruses on growth and pathogenicity
      of R. necatrix. Here, we extended the experimental host range of these two
      mycoviruses using a transfection approach. Protoplasts of other phytopathogenic
      Sordariomycetous fungi-Diaporthe sp., Cryphonectria parasitica, Valsa
      ceratosperma (Sordariomycetidae), and Glomerella cingulata (Hypocreomycetidae)
      were inoculated with RnPV1 and MyRV3 viral particles. The presence of double
      stranded RNA viral genomes in regenerated mycelia of Diaporthe sp., C.
      parasitica, and V. ceratosperma confirmed both types of viral infections in these
      three novel host species. An established RnPV1 infection was confirmed in G.
      cingulata but MyRV3 did not infect this host. Horizontal transmission of both
      viruses from newly infected strains to virus-free, wild-type strains through
      hyphal anastomosis was readily achieved by dual culture; however, vertical
      transmission through conidia was rarely observed. The virulence of Diaporthe sp.,
      C. parasitica, and V. ceratosperma strains harboring MyRV3 was reduced compared
      with their virus-free counterpart. In summary, our protoplast inoculation method
      extended the experimental host range of RnPV1-W8 and MyRV3 within the class
      Sordariomycetes and revealed that MyRV3 confers hypovirulence to the new hosts,
      as it does to R. necatrix.

PMID- 20701491
TI  - Prevalence, incidence, and spatial dependence of soybean mosaic virus in Iowa.
AB  - The prevalence of soybean fields with plants infected with Soybean mosaic virus
      (SMV) in Iowa is assumed to be random, because the primary source of the virus is
      SMV-infected seed. Data collected from 2,500 soybean fields sampled over a 3-year
      period as part of the Iowa Soybean Disease Survey (2005 to 2007) were used to
      evaluate this assumption. SMV was first detected in early June of each year but
      counties in which it was first detected varied among years. Prevalence at the
      county scale at end of season was 32.3, 27.3, and 89.9% in 2005, 2006, and 2007,
      respectively. End-of-season incidence of SMV within SMV-positive counties was 1.5
      to 25.0, 1.7 to 24, and 1.8 to 58% in 2005, 2006, and 2007, respectively. The
      number of fields in which plants infected with SMV were detected increased at the
      linear rate of approximately one new field every 2 days in 2007, compared with
      one new field every 22 days (2005) and 21 days (2006), with coefficients of
      determination (R2) of 93.2 to 96.8% using the linear model. Weak spatial
      dependence for end-of-season SMV incidence was detected using Moran's Index,
      indicating that the risk for SMV incidence at the county scale within Iowa at the
      end of the growing season is not random.

PMID- 20701492
TI  - Characterization of kudzu (Pueraria spp.) resistance to Phakopsora pachyrhizi,
      the causal agent of soybean rust.
AB  - Kudzu (Pueraria spp.) is an accessory host for soybean rust (SBR) (caused by
      Phakopsora pachyrhizi) that is widespread throughout the southeastern United
      States. An expanded survey of kudzu sites was conducted in 2008 to determine the
      proportion of natural resistance in the north-Florida kudzu population. Of the
      139 sites evaluated, approximately 18% were found to be free of SBR infection,
      while 23% had reduced sporulation. Ten accessions of kudzu from north-central
      Florida were characterized for their response to challenge by a single isolate of
      P. pachyrhizi under laboratory conditions. Three outcomes were observed: tan
      lesions with profuse sporulation (susceptible); reddish-brown lesions with
      delayed, reduced sporulation (resistant); and an immune response in which no
      lesions developed (immune). Of the 10 accessions, 6 were susceptible, 3 were
      immune, and 1 was resistant. Cytological examination revealed that resistant
      interactions were typified by early onset of a multicell hypersensitive response
      (HR) while typical immune interactions were the result of cell wall depositions
      that blocked penetration in combination with early onset of the HR. Quantitative
      real-time polymerase chain reaction was performed to determine the extent of
      colonization. After 15 days, there was 10-fold less P. pachyrhizi DNA present in
      resistant compared with susceptible kudzu, while the amount of P. pachyrhizi DNA
      present in the immune kudzu was below the detection level. Susceptible kudzu had
      approximately half the amount of P. pachyrhizi DNA present when compared with a
      susceptible soybean cultivar.

PMID- 20701493
TI  - Early events of citrus greening (Huanglongbing) disease development at the
      ultrastructural level.
AB  - Citrus greening (Huanglongbing [HLB]) is one of the most destructive diseases of
      citrus worldwide. The causal agent of HLB in Florida is thought to be 'Candidatus
      Liberibacter asiaticus'. Understanding of the early events in HLB infection is
      critical for the development of effective measures to control the disease. In
      this work, we conducted cytopathological studies by following the development of
      the disease in citrus trees graft inoculated with 'Ca. L. asiaticus'-containing
      material under greenhouse conditions to examine the correlation between
      ultrastructural changes and symptom production, with the main objective of
      characterizing the early events of infection. Based on our observations, one of
      the first degenerative changes induced upon invasion of the pathogen appears to
      be swelling of middle lamella between cell walls surrounding sieve elements. This
      anatomical aberration was often observed in samples from newly growing flushes in
      inoculated sweet orange and grapefruit trees at the early "presymptomatic" stage
      of HLB infection. Development of symptoms and their progression correlated with
      an increasing degree of microscopic aberrations. Remarkably, the ability to
      observe the bacterium in the infected tissue also correlated with the degree of
      the disease progression. Large numbers of bacterial cells were found in phloem
      sieve tubes in tissue samples from presymptomatic young flushes. In contrast, we
      did not observe the bacteria in highly symptomatic leaf samples, suggesting a
      possibility that, at more advanced stages of the disease, a major proportion of
      'Ca. L. asiaticus' is present in a nonviable state. We trust that observations
      reported here advance our understanding of how 'Ca. L. asiaticus' causes disease.
      Furthermore, they may be an important aid in answering a question: when and where
      within an infected tree the tissue serves as a better inoculum source for
      acquisition and transmission of the bacterium by its psyllid vector.

PMID- 20701494
TI  - Quantitative models for germination and infection of Pseudoperonospora cubensis
      in response to temperature and duration of leaf wetness.
AB  - The influence of temperature and leaf wetness duration on germination of
      sporangia and infection of cantaloupe leaves by Pseudoperonospora cubensis was
      examined in three independent controlled-environment experiments by inoculating
      plants with a spore suspension and exposing them to a range of leaf wetness
      durations (2 to 24 h) at six fixed temperatures (5 to 30 degrees C). Germination
      of sporangia was assessed at the end of each wetness period and infection was
      evaluated from assessments of disease severity 5 days after inoculation. Three
      response surface models based on modified forms of the Weibull function were
      evaluated for their ability to describe germination of sporangia and infection in
      response to temperature and leaf wetness duration. The models estimated 15.7 to
      17.3 and 19.5 to 21.7 degrees C as the optimum temperature (t) range for
      germination and infection, respectively, with little germination or infection at
      5 or 30 degrees C. For wetness periods of 4 to 8 h, a distinct optimum for
      infection was observed at t = 20 degrees C but broader optimum curves resulted
      from wetness periods >8 h. Model 1 of the form f(w,t) = f(t) x (1 - exp{-[B x
      w](D)}) resulted in smaller asymptotic standard errors and yielded higher
      correlations between observed and predicted germination and infection data than
      either model 2 of the form f(w,t) = A{1 - exp[- f(t) x (w - C)](D)} or model 3 of
      the form f(w,t) = [1 - exp{-(B x w)(2)}]/cosh[(t - F)G/2]. Models 1 and 2 had
      nonsignificant lack-of-fit test statistics for both germination and infection
      data, whereas a lack-of-fit test was significant for model 3. The models
      accounted for approximately 87% (model 3) to 98% (model 1) of the total variation
      in the germination and infection data. In the validation of the models using data
      generated with a different isolate of P. cubensis, slopes of the regression line
      between observed and predicted germination and infection data were not
      significantly different (P > 0.2487) and correlation coefficients between
      observed and predicted values were high (r(2) > 0.81). Models 1 and 2 were used
      to construct risk threshold charts that can be used to estimate the potential
      risk for infection based on observed or forecasted temperature and leaf wetness
      duration.

PMID- 20701495
TI  - Teaching ward rounds: what are the alternatives?

PMID- 20701496
TI  - Intermittent auscultation of fetal heart rate during labour - a widely accepted
      technique for low risk pregnancies: but are the current national guidelines
      robust and practical?
AB  - Intermittent auscultation of fetal heart rate is an accepted practice in low risk
      labours in many countries. National guidelines on intrapartum fetal monitoring
      were critically reviewed regarding timing and frequency of intermittent
      auscultation. Hypothetical but plausible examples are presented to illustrate
      that it may be possible to miss significant fetal distress with strict adherence
      to current guidelines. Opinion is forwarded that intermittent auscultation should
      be performed for 60 seconds before and after three contractions over about 10 min
      every half an hour in the first stage of labour. Reasons are put forward to show
      how this could be more practical and patient friendly and at the same time could
      improve detection of fetal distress. The current recommendation of intermittent
      auscultation every 15 min in the first stage is associated with poor compliance
      and leads to unnecessary burden, stress and medicolegal liability for birth
      attendants. Modification of current national guidelines would be desirable.

PMID- 20701497
TI  - Ward-based clinical teaching in gynaecology: principles and practice.
AB  - Clinical teaching on the wards remains a prime method of educational instruction.
      Despite changes in modern educational climate and patient expectations, its value
      is still irrefutable. There is evidence to suggest that such teaching is
      beneficial to students and patients alike. This paper describes the planning and
      delivery steps of a ward-based teaching session with 'pregnancy of unknown
      location' as an example. The organisation, following-up and feedback after the
      session are also mentioned. We have discussed the models applicable to clinical
      teaching and explored ways how the 'microskill' technique could be potentially
      used in such a situation. The paper also focuses on the use of clinical reasoning
      processes. Finally, the six domains of knowledge necessary to become a good
      preceptor have been applied to the session. A good teaching exercise is moored to
      sound pedagogical principles. Its success relies on mutual trust and
      understanding between the teacher and the taught.

PMID- 20701498
TI  - Delivery of the deeply engaged head: a lacuna in training.
AB  - The percentage of second stage caesarean sections is on the rise. The delivery of
      a deeply engaged head in the second stage by caesarean section is an experience
      feared by most junior registrars. Among the different delivery techniques
      described, the pull technique has been proven to have a lesser morbidity than the
      push technique. However, trainees do not receive any structured training in
      either of these methods. We undertook a survey among 150 UK trainees in SPROGS
      2008 in order to understand their experience in dealing with a deeply engaged
      head in second stage by CS, to ascertain whether trainees feel that they need
      training to deal with the situation and to discover the means by which this
      training can be delivered. The questionnaire return rate was 94%. More than 80%
      agreed that they had faced difficulties in the past while trying to deliver a
      deeply engaged head. Only 20% used the recommended semi-lithotomy position during
      caesarean section for an impacted head. Among the trainees who had received only
      UK training, only 42% were confident of doing a pull method if the need arose.
      More than 80% of the trainees agreed that supervised sessions to teach
      alternative techniques for delivery, such as the reverse breech/pull method would
      be useful and that it would improve their confidence when doing a trial of
      vaginal delivery. The RCOG agreed that there is little formal training in
      delivery of a deeply engaged head and is considering recommending trainees
      complete 2 OSATS (Objective Structured Assessment Tools) in this area. It has
      also asked the authors to form a skills and drills protocol, which the authors
      have done and submitted to the RCOG.

PMID- 20701499
TI  - Achieving continuous improvement in routine questioning about domestic violence
      with an embedded advocacy service.
AB  - Domestic violence (DV) is a common but underreported cause of morbidity in
      pregnant women. A retrospective review of maternity notes of 103 women who
      delivered October-November 2007, followed by prospective review of records after
      feedback intervention of 168 pregnant women who had nuchal a scan in February
      2008 was undertaken. The aim was to determine: (1) the proportion of women who
      were asked abuse questions at any time during pregnancy and postnatally; (2) the
      prevalence of disclosed domestic violence; (3) the sociodemographic predictors of
      a pregnant woman being asked about DV; (4) if feedback is associated with
      improved routine questioning. Routine enquiry about DV in pregnancy significantly
      increased from 53% in 2007 to 66% in 2008 (p < 0.05). Current DV was disclosed by
      3.6% of women in both surveys. Domestic violence is common in pregnancy. After
      implementation of training and an embedded DV advocacy service, routine enquiry
      demonstrated significant increase over time.

PMID- 20701500
TI  - Obstetric care at the intersection of science and culture: Swedish doctors'
      perspectives on obstetric care of women who have undergone female genital
      cutting.
AB  - Providing healthcare for women having undergone female genital cutting can
      present challenges. The women might require special obstetric care, including an
      anterior episiotomy (defibulation) for infibulated women. This paper explores how
      Swedish doctors caring for these women describe, explain and reason about their
      care and relevant policies in a Swedish context. A qualitative study was carried
      out with 13 chief/senior obstetricians and seven senior house officers. There was
      little consensus among the interviewed doctors on what constitutes good obstetric
      care for women with FGC or how care should be provided. Major problems include:
      inconsistent policy and praxis; uncoordinated care trajectories; diffuse
      professional role responsibilities; difficulties in monitoring labour and fetal
      status; and inhibited communication. The data highlight the need for increased
      awareness and reflective praxis both on the part of individual practitioners, and
      on an organisational level, which takes account of the special needs of different
      users.

PMID- 20701501
TI  - Conventional barium enema in early pregnancy.
AB  - X-ray exposure, especially if directed to the abdominal region, is of major
      concern for pregnant women and their physicians. In this study, favourable long
      term outcomes are reported in a series of babies born to women inadvertently
      exposed to barium enema, and associated ionising radiation, early in pregnancy.
      Six singleton babies were vaginally delivered without any evidence of gross
      malformations. There was one voluntary abortion. Follow-up on five of the babies
      was performed over the course of at least 4 years. All the children were deemed
      healthy and had developed milestones according to their age. Our findings support
      larger studies suggesting barium enema is not a teratogenic agent. Collectively,
      this research can be used to counsel women undergoing radiological procedures
      early in pregnancy.

PMID- 20701502
TI  - A prospective cohort study of pregnancy outcomes of women inadvertently exposed
      to methylephedrine in the 1st trimester of pregnancy.
AB  - No information is currently available on the safety of methylephedrine, a
      component of various cold medications available in South Korea. With previous
      approval by an Institutional Review Board, 349 women inadvertently exposed to
      methylephedrine during the 1st trimester of pregnancy and an age- and gravidity
      matched control group, were enrolled in a prospective cohort study. Study
      outcomes, for example gestational age at birth, birth weight and major and minor
      malformations were evaluated in 282 cases and 280 controls. Exposure to
      methylephedrine was at a gestational age of 4.0 weeks (median), at doses ranging
      from 52.5 to 1,575 mg/day, for a median duration of 3 (range: 1-30) days. No
      differences were observed between cases and controls in any of the pregnancy
      outcomes studied. There were 4/265 (1.5%) babies born with major malformations in
      the case group and 4/260 (1.5%) in the control group. In conclusion, inadvertent
      exposure to methylephedrine as a component of over-the counter oral cold remedies
      in early pregnancy was not associated with an increased rate of adverse pregnancy
      outcomes. Co-exposure with acetaminophen, cigarette smoking or alcohol did not
      appear to modify the outcomes.

PMID- 20701503
TI  - Failure to recognise the impact of 'moderate' obesity (BMI 30-40) on adverse
      obstetric outcomes.
AB  - Obesity is a growing epidemic in the western world. We carried out a comparative
      analysis of the incidence of obstetric morbidity in three BMI categories in the
      ranges 30-40 to identify which BMI category was associated with greatest risk.
      This identification could help target limited maternity care resources to the
      group of women who would benefit most. There exists a scale continuum of risk of
      obstetric morbidity with maternal obesity: the greater the BMI, the greater the
      risk. However, pregnant women with mild or moderate obesity are still at
      significant risk of having pre-existing co-morbidities of developing antenatal
      complications and of being delivered by caesarean section than women with BMIs
      within the normal range. These women, at the time of antenatal booking, are
      currently not perceived by healthcare providers as having at-risk pregnancies and
      are therefore potentially denied access to best care.

PMID- 20701504
TI  - The role of phosphorylated insulin-like growth factor binding protein-1 in
      predicting pre-term labour in twin pregnancies.
AB  - This was a retrospective study, carried out at Yeovil District Hospital, UK, from
      January 2006 to December 2008, looking at 40 patients with twin pregnancies. The
      aim was to evaluate the role of phosphorylated insulin-like growth factor binding
      protein-1 (IGFBP-1) test in the prediction of pre-term delivery in twin
      pregnancies. All the patients had a transvaginal ultrasound scan for cervical
      length at 24 weeks, followed by a high vaginal swab for IGFBP-1 at 26 weeks. A
      total of 95% of women screened negative for the IGFBP-1 test. None of these women
      delivered before 30 weeks; 7.50% delivered between 30 and 33+6 weeks; 87.5%
      delivered after 34 weeks. Two women (5.00%) screened positive for phosphorylated
      insulin-like growth factor binding protein-1; one had a spontaneous pre-term
      delivery at 30 weeks, while the other patient delivered at 38 weeks. It was
      concluded that women with twin pregnancies that have negative phosphorylated
      insulin-like growth factor binding protein-1 have a low risk of delivery before
      34 weeks in the absence of other obstetric complications.

PMID- 20701505
TI  - Comparison of short-term outcomes of late pre-term singletons and dichorionic
      twins and optimal timing of delivery.
AB  - This study examined the incidence of perinatal morbidity and mortality in late
      pre-term and term dichorionic twins versus singleton delivery at the same
      gestation. There were no measurable differences in the incidence of the perinatal
      complications in relation to gestational age at delivery between singleton and
      dichorionic twin pregnancies. In singleton pregnancies, the incidence of RDS/TTN
      in late pre-term births are significantly higher than those at 37 weeks, while
      the incidence in births at 39-40 weeks are significantly lower than those at 37
      weeks. In dichorionic twin pregnancies, the incidence of RDS/TTN in late pre-term
      births are significantly higher than those at 37 weeks, while there were no
      measurable differences in the incidence in births between 37 and 38-39 weeks'
      gestation. There were no cases of fetal demise in dichorionic twin pregnancies at
      36-40 weeks' gestation. Although fetuses in dichorionic twin pregnancies may
      achieve maturity earlier than fetuses in singleton pregnancies at 37-40 weeks'
      gestation, the incidence of perinatal complications such as RDS/TTN of late pre
      term births in dichorionic twin pregnancies was the same as that in singleton
      pregnancies. In the absence of maternal or fetal complications, it is advisable
      to deliver twins only at 37 completed weeks' gestation or later, to avoid
      neonatal complications.

PMID- 20701506
TI  - The management of reduced fetal movements in an uncomplicated pregnancy at term:
      results from an anonymous national online survey in the Republic of Ireland.
AB  - There is currently inconsistent evidence and clinical guidance on how to best
      manage a pregnancy complicated by reduced fetal movements. This novel, web-based,
      anonymous questionnaire evaluated 96 assessment and management approaches from
      doctors working in obstetrics in the Republic of Ireland who were presented with
      a clinical scenario of a primigravida concerned about reduced fetal movements at
      39+3 weeks' gestation. This study identified a lack of clinical practice
      guidelines available in maternity hospitals in the Republic of Ireland. We
      demonstrated that almost all clinicians applied more than one assessment method
      and that most incorporated a cardiotocograph into their assessment. There was a
      low uptake of simple symphysio-fundal height measurement and high usage of
      kickcharts. The minority of clinicians admitted or induced their patients. This
      survey identified the need for national and international guidelines to ensure
      safe antepartum care and delivery.

PMID- 20701507
TI  - Predictors of successful vaginal delivery after previous caesarean section in a
      Nigerian tertiary hospital.
AB  - Achieving a successful vaginal birth after a previous caesarean section (VBAC) is
      an important strategy in reducing the rising rate of caesarean section and its
      associated morbidities. Records of 188 women attempting trial of vaginal delivery
      after a previous lower segment caesarean section were reviewed to predict factors
      favouring successful vaginal delivery. Of the 188 women, 64 had recurrent
      indications for caesarean section, while 124 had non-recurrent indications. The
      group with recurrent indications for previous caesarean section had less vaginal
      delivery and more repeat caesarean sections as compared with the group with non
      recurrent indications (21.9% and 78.1% vs 46.8% and 53.2%, respectively, p =
      0.01). Cephalopelvic disproportion was more frequent in the group with recurrent
      indications (65.6% vs 27.4%, p < 0.0001). Significant predictors of successful
      VBAC in this cohort of women were non-recurrent indications for the previous
      caesarean section (p < 0.001, odds ratio (95% CI) 0.32 (0.2-0.6)) and a previous
      vaginal delivery (p < 0.0001, odds ratio (95% CI) 3.90 (2.1-7.4)). A previous
      vaginal delivery and a non-recurrent indication for the previous caesarean
      section are important predictors of VBAC in this cohort of women.

PMID- 20701508
TI  - Use of balloon catheter tamponade for massive postpartum haemorrhage.
AB  - Haemorrhage is one of the leading global causes of maternal mortality. The Rusch
      balloon has been used in the treatment of postpartum haemorrhage (PPH) after
      failure of medical management. It is often effective in tamponading uterine
      bleeding, thus providing an alternative to hysterectomy. We describe a series of
      22 cases in which we used the Rusch balloon to control massive obstetric
      haemorrhage after failure to control haemorrhage by medical means. In our study,
      13 out of 22 patients (59.1%) required no further interventions after balloon
      tamponade. Seven patients (31.8%) required hysterectomy to control the bleeding.
      We include a review of the current literature on balloon tamponade for PPH,
      including analysis of six relevant case series. This demonstrates a variety of
      methods based on tamponade to terminate uterine haemorrhage. Our study highlights
      the benefit of balloon tamponade for massive PPH and the importance of its
      involvement in labour ward protocols.

PMID- 20701509
TI  - Caesarean delivery rates in Turkish adolescents.

PMID- 20701511
TI  - Anaesthesia for incontinence surgery: spinal anaesthesia or sedation?
AB  - This was a patient and assessor blinded randomised controlled trial to compare
      the patient and surgeon's satisfaction for retropubic tapes inserted under
      sedation vs spinal anaesthesia and also looking at the bladder sensation
      following insertion of the tape. A total of 38 patients completed the study (19
      in each group). The differences in mean visual analogue scores were in favour of
      spinal anaesthesia. The surgeon's assessment of patient cooperation was 24.2, 95%
      CI 9.6-38.8 p = 0.002, while for pain, the difference in the mean scores was 
      21.6, 95% CI -36.6 to -6.5, p = 0.006. The difference in the mean scores for the
      feeling of being in control was 21.4, 95% CI 0.85 to 41.63, p = 0.004. The only
      significant difference in bladder sensation postoperatively was the strong desire
      to void at 1 hour. This study demonstrates that spinal anaesthesia has better
      patient and surgeon satisfaction, with a difference in bladder sensation at 1
      hour postoperatively.

PMID- 20701512
TI  - Outcomes from medium term follow-up of patients with third and fourth degree
      perineal tears.
AB  - Third and fourth degree perineal tears have a considerable bearing on a woman's
      future continence and quality of life. The RCOG recommends that all symptomatic
      women or those with abnormal anorectal manometric or endoanal ultrasonographic
      features should have the option of caesarean birth. We assessed the outcomes of
      79 such women with regard to their symptoms, endoanal ultrasound and manometry
      findings at 6 months after delivery and the mode of delivery in the subsequent
      pregnancy. Some 85% of the patients were asymptomatic. Five patients (42%) had
      faecal incontinence and the scarring was the commonest finding on endoanal
      ultrasound, irrespective of symptoms. The anal manometry showed reduced squeeze
      and resting pressures in proportionately higher numbers of symptomatic patients.
      A total of 12 patients underwent a caesarean section in their next pregnancy.
      Three patients had a repeat third degree tear. Among those who failed to keep the
      colorectal appointment, we conducted a telephonic questionnaire and found that
      most women (32 out of 33) were asymptomatic and three women were reluctant to be
      examined by a male doctor. We recommend appropriate identification, repair,
      physiotherapy and multidisciplinary follow-up in these patients to improve long
      term outcomes.

PMID- 20701510
TI  - The ATAC adjuvant breast-cancer trial: six-year results of the endometrial
      subprotocol.
AB  - Postmenopausal women with localised, early breast cancer (n = 285) were enrolled
      in a prospective subprotocol of the 'arimidex, tamoxifen, alone or in
      combination' (ATAC) trial to assess gynaecological abnormalities arising during
      treatment with anastrozole (1 mg/day) or tamoxifen (20 mg/day). After 6 years'
      follow-up, there appeared to be non-significantly fewer endometrial abnormalities
      with anastrozole than with tamoxifen (12.4% vs 20.2%, odds ratio 0.52; 95%
      confidence intervals 0.20, 1.32; p = 0.17). The time to first endometrial
      abnormality was non-significantly longer for patients receiving anastrozole
      compared with tamoxifen (hazard ratio 0.57; 95% confidence intervals 0.26, 1.22;
      p = 0.15), with most abnormalities occurring within the first year of treatment.
      Fewer patients treated with anastrozole appeared to require medical intervention
      for endometrial abnormalities, compared with patients on tamoxifen. This study
      showed that there was no significant difference in endometrial pathology between
      anastrozole and tamoxifen treatment groups.

PMID- 20701513
TI  - Application of EU tissue and cell directive screening protocols to anonymous
      oocyte donors in western Ukraine: data from an Irish IVF programme.
AB  - Anonymous oocyte donation in the EU proceeds only after rigorous screening
      designed to ensure gamete safety. If anonymous donor gametes originating from
      outside EU territory are used by EU patients, donor testing must conform to the
      same standards as if gamete procurement had occurred in the EU. In Ireland, IVF
      recipients can be matched to anonymous donors in the Ukraine (a non-EU country).
      This investigation describes the evolution of anonymous oocyte donor screening
      methods during this period and associated results. Data were reviewed for all
      participants in an anonymous donor oocyte IVF programme from 2006 to 2009, when
      testing consistent with contemporary EU screening requirements was performed on
      all Ukrainian oocyte donors. HIV and hepatitis tests were aggregated from 314
      anonymous oocyte donors and 265 recipients. The results included 5,524 Ukrainian
      women who were interviewed and 314 of these entered the programme (5.7% accession
      rate). Mean age of anonymous oocyte donors was 27.9 years; all had achieved at
      least one delivery. No case of hepatitis or HIV was detected at initial screening
      or at oocyte procurement. This is the first study of HIV and hepatitis incidence
      specifically among Ukrainian oocyte donors. We find anonymous oocyte donors to be
      a low-risk group, despite a high background HIV rate. Following full disclosure
      of the donation process, most Ukrainian women wishing to volunteer as anonymous
      oocyte donors do not participate. Current EU screening requirements appear
      adequate to maintain patient safety in the context of anonymous donor oocyte IVF.

PMID- 20701514
TI  - Clomiphene citrate or aromatase inhibitors combined with gonadotropins for
      superovulation in women undergoing intrauterine insemination: a prospective
      randomised trial.
AB  - The objective of this study was to test the use of letrozole in combination with
      follicle-stimulating hormone (FSH) vs clomiphene citrate (CC) with FSH for
      ovarian hyperstimulation prior to intrauterine insemination (IUI). A prospective
      randomised trial in which 280 women with unexplained infertility were randomised
      to 100 mg of CC (141 patients, 219 cycles) or 5 mg of letrozole daily (139
      patients, 215 cycles) for 5 days starting on day 3 of menses both combined with
      gonadotropins for ovarian stimulation prior to IUI. The primary outcome measures
      were the number of growing and mature follicles, the concentrations of serum E2
      (pg/ml) and progesterone (ng/ml), and the endometrial thickness (mm). The
      secondary outcome measure was the occurrence of pregnancy and miscarriage. The
      total number of follicles was significantly greater in the CC group (4.1 +/- 0.46
      vs 2.6 +/- 0.43). There was no significant difference in endometrial thickness
      between the two groups. Pregnancy occurred in 33 out of 139 patients (215 cycles)
      in the letrozole group (23.7% and 15.3%, respectively) and 37 out of 141 patients
      (219 cycles) (26.2% and 16.8%, respectively) in the CC group; the differences
      were not statistically significant. The allied use of either CC or letrozole,
      during ovarian stimulation to reduce the dose of gonadotropins prior to IUI is
      justified. This approach will reduce the cost of stimulation protocols without
      effect on the treatment outcome and letrozole has no advantage over CC in this
      respect.

PMID- 20701515
TI  - Fetal loss in threatened abortion after demonstration of fetal cardiac activity
      in a low socioeconomic population.
AB  - This study was conducted to determine the incidence and risk factors of fetal
      loss in threatened abortion after ultrasonographic detection of fetal cardiac
      activity in a low socioeconomic population. A total of 202 women with singleton
      pregnancies who presented with vaginal bleeding in which fetal heart activity was
      ultrasonographically demonstrated between 5 and 14 weeks' gestation were
      included. Pregnancies with fetal abnormalities were excluded from the study. All
      cases were followed-up with respect to pregnancy outcomes. A total of 54 of 202
      pregnancies (26.7%) resulted in fetal loss before 20 weeks' gestation. The mean
      fetal heart rate (FHR) and cervical length values were lower in spontaneous
      abortions than in viable pregnancies (121.2 +/- 13.3 vs 143.5 +/- 12.4 and 41 +/-
      6.0 vs. 34.8 +/- 6.1, respectively; p < 0.001). A receiver operating
      characteristic (ROC) curve analysis revealed an area under the curve of 0.88 for
      FHR and 0.77 for cervical length. A FHR value <130 b.p.m. was 81.4% sensitive,
      85.1% specific and a cervical length value <40 mm was 80.8% sensitive, 54.7%
      specific for determination of fetal loss before 20 weeks' gestation. Fetal loss
      was observed in about one-quarter of pregnancies admitted with threatened
      abortion in a low socioeconomic population. Bradycardia and short cervix were
      found to be significant risk factors affecting the pregnancy outcome in women
      presenting with vaginal bleeding, in whom fetal cardiac activity was documented.

PMID- 20701516
TI  - Heterotopic caesarean section scar pregnancy.

PMID- 20701517
TI  - Trisomy 22: the heart aspect.

PMID- 20701518
TI  - Prenatal diagnosis of thanatophoric dysplasia and obstetrical challenges.

PMID- 20701519
TI  - Role of flow cytometry in mothers with hereditary persistence of fetal
      haemoglobin.

PMID- 20701520
TI  - Neonatal aspiration syndrome complicating a water birth.

PMID- 20701521
TI  - Perforated duodenal ulcer in the immediate puerperium following caesarean
      section.

PMID- 20701522
TI  - Unusual presentation of genital tract tuberculosis.

PMID- 20701523
TI  - Primary hydatid disease presenting as a pelvic mass.

PMID- 20701524
TI  - Torsion of the testicle in a patient with complete androgen insensitivity
      syndrome.

PMID- 20701525
TI  - The management of cervical glandular intraepithelial neoplasia during pregnancy.

PMID- 20701526
TI  - An unusual case of post-traumatic endometriosis involving the sciatic nerve in
      the right greater sciatic notch.

PMID- 20701531
TI  - Behavioral plasticity allows short-term adjustment to a novel environment.
AB  - Many species are currently experiencing anthropogenically driven environmental
      changes. Among these changes, increasing noise levels are specifically a problem
      for species relying on acoustic communication. Recent evidence suggests that some
      species adjust their acoustic signals to man-made noise. However, it is unknown
      whether these changes occur through short-term and reversible adjustments by
      behavioral plasticity or through long-term adaptations by evolutionary change.
      Using behavioral observations and playback experiments, we show that male reed
      buntings (Emberiza schoeniclus) adjusted their songs immediately, singing at a
      higher minimum frequency and at a lower rate when noise levels were high. Our
      data showed that these changes in singing behavior were short-term adjustments of
      signal characteristics resulting from behavioral plasticity, rather than a long
      term adaptation. However, more males remained unpaired at a noisy location than
      at a quiet location throughout the breeding season. Thus, phenotypic plasticity
      enables individuals to respond to environmental changes, but whether these short
      term adjustments are beneficial remains to be seen.

PMID- 20701533
TI  - Combination lipid therapy in type 2 diabetes.

PMID- 20701534
TI  - Blood pressure control in type 2 diabetes.

PMID- 20701535
TI  - Bar-code technology to reduce medication errors.

PMID- 20701537
TI  - Hepatitis delta: seek and ye shall find.

PMID- 20701536
TI  - Prevalence, correlates, and viral dynamics of hepatitis delta among injection
      drug users.
AB  - BACKGROUND: Most hepatitis delta virus (HDV) prevalence estimates from the United
      States are >10 years old, and HDV has shown significant temporal variation in
      other populations. HDV-hepatitis B virus (HBV) dual infection progresses rapidly,
      has more complications, and has a different treatment regimen than HBV infection
      alone. Accurate estimates of prevalence and risk factors are important to help
      clinicians decide who to screen. METHODS: Injection drug users in Baltimore,
      Maryland, who were positive for HBV serologic markers were tested for hepatitis
      delta antibody (HDAb) at 2 time periods: 1988-1989 (194 participants) and 2005
      2006 (258 participants). Those who were HDAb positive in 2005-2006, plus a random
      sample of HDAb negative, HBV-positive participants were tested for HDV RNA, HBV
      DNA, and HCV RNA. Characteristics associated with HDV exposure and viremia were
      identified. RESULTS: HDV prevalence declined from 15% in 1988-1989 to 11% in 2005
      2006. Among those with chronic HBV infection, prevalence increased from 29% (14
      of 48 participants) to 50% (19 of 38 participants) (P=.05). Visiting a "shooting
      gallery" (a location where people gather to inject illegal drugs) was a strong
      correlate of HDAb positivity (relative risk, 3.08; P=.01). Eight (32%) of those
      who were HDAb positive had HDV viremia. Viremic participants had elevated liver
      enzyme levels and more emergency room visits. CONCLUSIONS: The temporal increase
      in HDV prevalence among those with chronic HBV infection is troubling;
      understanding this change should be a priority to prevent the burden from
      increasing.

PMID- 20701539
TI  - Transposons related to Tn1696 in IncHI2 plasmids in multiply antibiotic resistant
      Salmonella enterica serovar Typhimurium from Australian animals.
AB  - Conjugative IncHI2 plasmids carrying tetracycline, trimethoprim, and sulphonamide
      resistance genes were recovered from two multiply antibiotic resistant Salmonella
      enterica serovar Typhimurium isolates from Australian food-producing animals.
      Transposons related to the mercury resistance transposon Tn1696 were identified
      in both IncHI2 plasmids. These transposons contained an In4-type class 1 integron
      that carried a dfrA5 trimethoprim resistance gene cassette and the sul1
      sulfonamide resistance gene. These integrons were located in the same position as
      In4 in Tn1696. The integron from one isolate includes a large transposon-like
      structure containing four IS26 and the strAB, sul2, bla(TEM), and aphA1 genes
      conferring resistance to streptomycin, sulphonamides, ampicillin, kanamycin, and
      neomycin, respectively. This structure is flanked by an 8-bp duplication, but it
      includes both the aphA1-containing transposon Tn4352 and a transposon, Tn6029,
      carrying genes derived from RSF1010 and from Tn2. However, Tn4352 and Tn6029
      overlap, sharing one IS26 copy. This suggests that they do not move by a standard
      transpositional mechanism. A circular intermediate, carrying only the region
      containing the resistance gene(s) and one of the IS26 bounding it, is proposed as
      an intermediate.

PMID- 20701538
TI  - Mycobacterium tuberculosis MT2816 encodes a key stress-response regulator.
AB  - BACKGROUND: Sigma (sigma) factors are transcription initiation factors that
      modulate the response of Mycobacterium tuberculosis to changes in extracellular
      milieu, allowing it to survive stress. METHODS: We analyzed the expression of
      MT2816/Rv2745c under various stress conditions that mimic the intracellular
      environment faced by M. tuberculosis. RESULTS: MT2816/Rv2745c expression was
      induced in M. tuberculosis following redox stress, heat shock and acid shock and
      intracellular replication. Its expression was also induced by SDS and
      thioridazine, agents that impact M. tuberculosis cell-envelope. However, exposure
      to isoniazid or ethambutol, front-line antituberculosis drugs which also target
      the cell envelope, did not induce the expression of MT2816/Rv2745c. Studies using
      Delta-sigma(H) and Delta-sigma(E) mutants showed that sigma(H) was required for
      the induction of MT2816/Rv2745c. Conditional expression of the MT2816/Rv2745c in
      M. tuberculosis showed that apart from regulating proteolysis, this gene may
      control the expression of trehalose biosynthesis and impact the maintenance of
      cellular redox potential and energy generation. CONCLUSIONS: The protein encoded
      by MT2816/Rv2745c is important for the pathogen's response to stress conditions
      that mimic in vivo growth and it is subject to complex regulation. The
      MT2816/Rv2745c encoded protein likely functions by protecting intracellular redox
      potential and by inducing the expression of trehalose, a constituent of M.
      tuberculosis cell walls that is important for defense against cell-surface and
      oxidative stress.

PMID- 20701540
TI  - Influence of specific blocking of the delta-like ligand 4/notch signal
      transduction pathway on the biological behavior of human umbilical vein
      endothelial cells.
AB  - The influence of specific blocking of the Delta-like ligand 4 (DLL4)/Notch signal
      transduction pathway on the biological behavior of human umbilical vein
      endothelial cells (HUVECs) has been studied. Recombinant adeno-associated virus
      (rAAV) vectors expressing an active small interfering RNA (siRNA) (vector 6)
      targeting the DLL4 (rAAV-DLL4-short hairpin RNA [shRNA]) was used to infect
      HUVECs. The same cell line infected with empty plasmid (rAAV-EGFP) was used as a
      control. Stable transfection and expression of DLL4-mRNA in HUVECs were
      determined by semiquantitative RT-polymerase chain reaction (PCR). Protein
      expression of DLL4 was examined by western blotting. The distribution of cells in
      cell cycle was assessed by flow cytometry and cell growth was analyzed by MTT
      assay. HUVECs were seeded on type I collagen and cultured in a three-dimensional
      culture system to allow for tubule-like structure (TLS) formation. Compared with
      negative controls, semiquantitative RT-PCR and western blot analysis showed that
      the expression of DLL4 mRNA and protein was downregulated in stably transfected
      cells (p = 0.024, p = 0.033). HUVEC growth and proliferation were stimulated
      following infection with rAAV vectors containing active siRNA against DLL4,
      whereas infection with empty plasmid had no specific effect. The proliferation
      index of rAAV-DLL4-shRNA-infected HUVECs was 39.90% +/- 2.19% compared with
      25.63% +/- 4.54% (p = 0.036) for control-treated cells. TLS formation was
      significantly induced in cells expressing the rAAV vector; the average length of
      TLS was greater than the control group (p = 0.028). Altogether, the data suggest
      that inhibiting the DLL4/Notch signal transduction pathway stimulated
      proliferation of HUVECs, thereby facilitating angiogenesis.

PMID- 20701541
TI  - Immunotherapy with cytokine-induced killer cells in metastatic renal cell
      carcinoma.
AB  - Cytokine-induced killer (CIK) cells have shown antitumor activity against several
      tumor cells both in vitro and in vivo. This study reports on the large-scale
      expansion of CIK cells and also present preliminary results from a pilot clinical
      trial. Sixteen (16) patients with renal cell carcinoma (RCC), all of whom had
      metastases after radical nephrectomy and adjuvant therapy using interferon-alpha
      (IFN-alpha) and/or interleukin-2 (IL-2), were treated with CIK cells. CIK cells
      were generated from peripheral blood mononuclear cells (PBMCs) and incubated in
      the presence of IFN-gamma followed by OKT3 and IL-2. Treatment schedule consisted
      of two to three cycles of CIK cell infusions at an interval of 3 weeks. A total
      of 46 infusions were administered to 16 metastatic RCC (mRCC) patients. The
      median number of transferred cells per treatment was 6.7 x 10(9) (range, 2.5
      12.3). At a 60:1 effector-target cell ratio, CIK cells killed 51.4% and 32.1% of
      two human kidney tumor cell lines (293 and SK-RC-42), respectively. After CIK
      cell infusion, the percentage of CD3(+), CD8(+), CD3(+)CD56(+), and NKG2D(+)
      cells and the intracellular products of two type 1 cytokines (IFN-gamma and tumor
      necrosis factor alpha) significantly increased in the patients' PBMCs. Toxicity
      was minimal, and there were no immediate adverse reactions to the infusions.
      Three (3) patients had complete response, 1 patient had partial response, and 6
      patients had stable disease. These results showed that adoptive CIK cell
      immunotherapy is a safe and effective treatment, which may have essential
      benefits for the improvement of the immunologic function in mRCC patients and
      play an important role in the treatment of mRCC.

PMID- 20701542
TI  - Radioprotection by alpha-lipoic acid palladium complex formulation (POLY-MVA) in
      mice.
AB  - The dietary supplement, POLY-MVA, containing palladium alpha-lipoic acid complex
      was examined for its efficacy as a radioprotector in mice exposed to whole-body
      gamma-radiation. Oral administration of POLY-MVA enhanced endogenous spleen
      colony formation in animals exposed to a sublethal dose of 6 Gy gamma-radiation.
      Alkaline comet assay revealed that the nuclear DNA comet parameters such as
      percent DNA in tail, tail length, tail moment, and olive tail moment, of the bone
      marrow cells and spleen cells, were found increased following whole-body gamma
      irradiation. The radiation-induced DNA damage in these cells was reduced when
      POLY-MVA was administered to animals exposed to a lethal dose of 8 Gy whole-body
      gamma-radiation. The administration of POLY-MVA significantly reduced the gamma
      radiation-induced mortality and also aided recovery from the radiation-induced
      loss of body weight in mice surviving after 8 Gy gamma-radiation exposure. These
      results suggest the potential use of POLY-MVA as a radioprotector in cases of
      planned radiation exposures.

PMID- 20701543
TI  - Influence of laser photobiomodulation on collagen IV during skeletal muscle
      tissue remodeling after injury in rats.
AB  - OBJECTIVE: The aim of the present study was to determine the effect of GaAlAs low
      level laser therapy (LLLT) on collagen IV remodeling of the tibialis anterior
      (TA) muscle in rats after cryolesion. BACKGROUND: Considerable interest exists in
      skeletal muscle regeneration in situations such as repair after exercise-induced
      muscle injury, after muscle transplantation, in muscular dystrophy, exercise
      induced muscle injury, and the recovery of strength after atrophy due to disuse.
      A number of studies have demonstrated the potential of LLLT in facilitating the
      muscle-healing process; however, no consensus is found in the literature
      regarding the best laser-irradiation parameters. METHODS: Adult male Wistar rats
      (n = 45) were used and randomly divided into three groups: control (n = 5);
      nontreated cryolesioned group (n = 20), and LLLT-cryolesioned group (n = 20). The
      cryolesioned groups were analyzed at 1, 7, 14, and 21 days after the injury
      procedure. Laser irradiation was performed 3 times per week on the injured region
      by using the GaAlAs laser (660 nm; beam spot of 0.04 cm(2), output power of 20
      mW, power density of 500 mW/cm(2), and energy density of 5 J/cm(2), for 10 sec).
      The muscles were removed, frozen, cryosectioned, and then stained with
      hematoxylin-eosin for the visualization of general morphology or used for
      immunohistochemical analysis of collagen IV. RESULTS: It was demonstrated that
      LLLT promotes an increase in collagen IV immunolabeling in skeletal muscle in the
      first 7 days after acute trauma caused by cryoinjury, but does not modify the
      duration of the tissue-repair process. Even with LLLT, the injured muscle tissue
      needs ~21 days to achieve the same state of organization as that in the
      noninjured muscle. CONCLUSION: The collagen IV content is modulated in
      regenerating skeletal muscle under LLLT, which might be associated with better
      tissue outcome, although the histologic analysis did not detect tissue
      improvement in the LLLT group.

PMID- 20701544
TI  - Should we be concerned about jejunoileal atresia during repair of duodenal
      atresia?
AB  - INTRODUCTION: During repair for duodenal atresia, it has been emphasized that
      inspection of the small bowel to identify a second atresia is required. The
      laparoscopic approach for repair of duodenal atresia has been criticized for its
      limitation to perform this step. Given that duodenal atresia and jejunoileal
      atresias do not share common embryologic origins, we question the validity of
      this concern. Therefore, we conducted a multicenter retrospective review of
      duodenal atresia patients to quantify the incidence of jejunoileal atresia in
      this population. METHODS: After institutional review board approval (IRB #07-12
      187X), a retrospective review was conducted on all patients who have undergone
      duodenal atresia repair at seven institutions over the past 7-12 years.
      Demographics and the presence or absence of a jejunoileal atresia were recorded.
      RESULTS: Four hundred eight patients with duodenal atresia were identified. The
      mean gestaational age was 36.3 +/- 2.9 weeks, and the mean weight was 2.5 +/- 0.8
      kg. Mean age at operation was 19 days (range, 1-1314). There was a 28% incidence
      of trisomy 21. Two patients (0.5%) were identified as having a second intestinal
      atresia, and both were type IIIb. One patient was diagnosed at the time of
      duodenal atresia repair; the other was a delayed diagnosis. Both patients did
      well after repair. CONCLUSIONS: In this, the largest series of duodenal atresia
      patients compiled to date, the rate of a concomitant jejunoileal atresia is less
      than 1%. This low incidence is not high enough to mandate extensive inspection of
      the entire bowel in these patients, and a second atresia should not be a concern
      during laparoscopic repair of duodenal atresia.

PMID- 20701545
TI  - Multidimensional analysis of the learning curve for laparoscopic rectal cancer
      surgery.
AB  - BACKGROUND: The need for an initial learning experience in laparoscopic
      colorectal cancer surgery has been well established. However, the inherent
      differences in the complexity and results of laparoscopic rectal cancer surgery,
      as compared to colon surgery, warrant a study to analyze the learning curve
      exclusively for rectal cancer resections. MATERIALS AND METHODS: four hundred
      thirty-one patients operated on between April 1994 and March 2006 were analyzed
      retrospectively for changes in surgical outcomes according to case sequence. A
      multidimensional analysis was done, based on the following parameters: conversion
      to laparotomy, intraoperative complications, postoperative complications,
      reoperations, operative time, and transfusion volumes. Multiple statistical
      methods were used for evaluation of the learning curve, which included the
      cumulative sum (CUSUM) method, risk-adjusted CUSUM, moving average method, and
      analysis of variance (ANOVA). RESULTS: The risk factors for conversion were prior
      abdominal surgery (hazard ratio, 2.52; 95% CI, 1.04-6.10; P = 0.04) and tumor
      size > or =3.5 cm (hazard ratio, 5.05; 95% CI, 1.95-13.08; P = 0.001). Risk
      adjusted CUSUM analysis showed that case 61 was the peak change point for
      conversion. Postoperative complications occurred in 56 patients (13.0%), and the
      rate was associated significantly with case sequence (P < 0.001). The turning
      point in the CUSUM model occurred at case 79, and the complication rates
      decreased thereafter. Operative time and intraoperative transfusion volumes
      stabilized over cases 61-75 and declined thereafter. CONCLUSIONS:
      Multidimensional analysis considering various surgical outcomes is necessary to
      evaluate the learning curve for laparoscopic rectal cancer surgery. The effective
      surgical learning curve was approximately 60-80 procedures in this series.

PMID- 20701546
TI  - Laparoscopic intracapsular myomectomy: comparison of single versus multiple
      fibroids removal. An institutional experience.
AB  - OBJECTIVE: The aim of this study was to compare single versus multiple
      laparoscopic myomectomy with an intracapsular method. STUDY DESIGN: A total of
      335 laparoscopic intracapsular myomectomies were compared. They were subdivided
      into two groups. Group I included 195 patients with myoma; group II, 140 patients
      with multiple myomas, 4-9 cm in diameter. Laparoscopic procedures were compared
      with respect to intraoperative complications, postoperative compliance, and
      general surgical feedback. Results were analyzed using SAS software (version 8),
      considering a P-value of <0.05 as significant. RESULTS: No differences (P>0.05)
      between groups were observed with respect to the following: intraoperative blood
      loss (98 +/- 4.7 mL of group I versus 106 +/- 6.8 mL of group II), catheter
      inside pelvis for postsurgical drainage (40% versus 36.4% women), analgesic
      administration for the first 24 hours (41.5% versus 40% patients), postoperative
      fever after 24 hours (11.2% versus 9.2% women), postoperative therapeutic
      antibiotics administration (8.2% versus 6.4% patients), and hospitalization and
      postoperative ultrasound (US) intramyometrial hematoma detection (6.6% versus
      5.7% of group II). The only surgical statistical difference (P<0.05) was in the
      mean total laparoscopic time (60 +/- 7.2 minutes for group I versus 97 +/- 8.9
      minutes for group II). CONCLUSIONS: Intracapsular laparoscopic myomectomies,
      performed in the same session on a single or on multiple fibroids, seem to
      preserve myometrial integrity and allow the restoration of uterine scar, with few
      early and late surgical complications.

PMID- 20701547
TI  - Shoulder pain following laparoscopic cholecystectomy: factors affecting the
      incidence and severity.
AB  - BACKGROUND: Laparoscopic cholecystectomy (LC) has become the standard treatment
      for gall bladder disease. However, despite its low degree of invasiveness, many
      patients complain of postoperative pain and postoperative nausea/vomiting. This
      study was planned to evaluate different factors affecting the incidence and
      severity of postoperative shoulder-tip pain after LC. PATIENTS AND METHODS: One
      hundred consecutive patients who were treated for gall bladder stone by LC at the
      Gastroenterology Surgical Center, Mansoura University, Mansoura, Egypt, during
      the period from October 2008 to January 2010, were randomized according to
      different pnemoperitonum pressures (8, 10, 12, and 14 mm Hg). Each group
      comprises 25 patients. RESULTS: There were 62 patients reported to have
      postoperative shoulder-tip pain during the first 12 hours after operation, which
      decreased to 9 patients on the 10th postoperative day. A significant difference
      was observed in the prevalence of pain at different pressures, 11% with low
      pressure and increased to 20% with high pressure. The incidence of shoulder-tip
      pain was significantly more in patients with a longer duration of the operation
      of >45 minutes at 12 hours (23 [76.7%] versus 39 [55.7%]; P = 0.04), at 24 hours
      (23 [76.7%] versus 29 [41.4%]; P = 0.009), and at 3 days postoperatively (19
      [63.3%] versus 20 [28.6%]; P = 0.01). The volume of used gases during the
      operation had no effect on the incidence or severity of shoulder-tip pain after
      LC. Also, the use of intraoperative analgesics had no effect on the incidence or
      severity of shoulder-tip pain after LC. CONCLUSIONS: The origin of pain after LC
      is multifactorial. We recommend the use of the lower pressure technique during
      LC, and as patients with and without drains have similar incidence of
      postoperative shoulder pain, drains should not be used with the intention of
      preventing shoulder pain.

PMID- 20701548
TI  - Optimization of the microwave-assisted extraction conditions of tea polyphenols
      from green tea.
AB  - Green tea, a popular drink with beneficial health properties, is a rich source of
      polyphenols that have a wealth of physiological activities. The purpose of the
      present study was to develop a microwave-assisted extraction (MAE) of green tea
      polyphenols. MAE of tea phenols from green tea was investigated through
      orthogonal array design. The content of total phenols in tea infusions was
      determined using UV/vis spectrophotometric methods. Four factors (microwave
      intensity, microwave irradiate time, microwave irradiate number of times and
      tea/water ratio) have a substantial impact on the extraction. The extraction
      conditions of tea polyphenols are optimized, and the order of importance that
      influenced the extraction rate was found to be: microwave radiate time>microwave
      intensity>tea/water ratio>radiate number of times, and the optimal performance of
      extraction was obtained under microwave intensity 600 W, microwave radiate time 3
      min and microwave radiate number of times once with tea/water ratio 1:20.MAE
      offers important advantages over conventional methods, such as shorter extraction
      times, substantial savings of energy and a reduced environmental burden.

PMID- 20701549
TI  - Point-of-use micronutrient fortification: lessons learned in implementing a
      preschool-based pilot trial in South Africa.
AB  - This current pilot trial assessed the feasibility of implementing a point-of-use
      (PoU) micronutrient fortification in preschool settings. Preschool children (n =
      151) aged 36-79 months were randomized into intervention (n = 76) and control (n
      = 75) groups, both receiving breakfast maize-porridge with added micronutrient or
      placebo powder for 52 school days. Process evaluation and early childhood
      development indicators were used to assess trial feasibility. Process evaluation
      results showed that the implementation components were feasible and could be
      delivered with high fidelity. The improvement in hemoglobin concentration in
      intervention and control groups were not significantly different (P = 0.250).
      There was medium likelihood for practical significance for the two global
      cognitive scores assessed: non-verbal index (intervention effects: 7.20; 95%
      confidence interval: 2.60, 11.81; P = 0.002, effect size: 0.55) and mental
      processing index (intervention effects: 2.73; 95% confidence interval: 0.25,
      5.70; P = 0.072, effect size: 0.36) on the Kaufman Assessment Battery for
      Children, Second Edition. The lessons from this trial could help in
      planning/implementing future PoU micronutrient fortification trial among South
      African preschool children.

PMID- 20701550
TI  - Tissue microarray-based immunohistochemical study can significantly underestimate
      the expression of HER2 and progesterone receptor in ductal carcinoma in situ of
      the breast.
AB  - The accuracy of immunohistochemical (IHC) analysis on tissue microarray (TMA)
      based studies largely depends on the uniformity of the staining pattern for a
      given antibody and minimal intratumor heterogeneity of a given tumor. Our study
      was designed to investigate the concordance of expression in TMA and whole
      sections of estrogen receptor (ER), progesterone receptor (PR) and HER2 using IHC
      analysis for ductal carcinoma in situ (DCIS) of the breast. Seventy-five
      consecutive cases of DCIS were retrieved, reviewed and used to construct the TMA.
      IHC analysis of the expression of ER, PR, and HER2 were performed on TMA and
      whole sections of the corresponding cases, and the results were compared. The
      specificity and sensitivity for TMA-based assays were 87.0, 75.9, 90.6 and 90.4%,
      and 76.1, 27.3 for ER, PR and HER2, respectively. The concordance and discordance
      were 89.3, 76.0 and 72.0%, and 6.7, 13.3 and 16.0% for ER, PR, HER2,
      respectively. The kappa values were 0.83, 0.89 and 0.42 for ER, PR and HER2,
      respectively. The non-concordance rates were inversely related to core number,
      with 46.67, 22.67 and 11.56% for one core, two cores, and three cores,
      respectively, per marker per case (p < 0.001), but not associated with tumor
      size. Our results showed that the intratumor heterogeneity and the number of
      cores have a great impact on the results of TMA-based studies. Increasing the
      number of tissue cores per case may help improve the accuracy and concordance
      with whole section results. Although TMA remains an effective tool for
      translational research, we should be cautious in our interpretation of these
      results.

PMID- 20701551
TI  - Whole-mount bone and cartilage staining of chick embryos with minimal
      decalcification.
AB  - Whole-mount staining with Alcian blue for cartilage and alizarin red for bone has
      been widely used for visualizing the skeletal patterns of embryos and small adult
      vertebrates. The possibility of decalcification by the acidic Alcian blue
      solution is known, but standard staining protocols do not always avoid this
      issue. We investigated the effects of acidity on the stainability of developing
      bones in stage 36 chick embryos and developed an optimal procedure for obtaining
      reliable results with minimal decalcification. The diaphyses of long bone
      rudiments and the maxillofacial membranous bones progressively lost their
      stainability with alizarin red when the chick embryos were soaked for long
      periods in the preceding acidic Alcian blue staining solution for cartilage.
      Unless the acidity was neutralized with an alkaline solution, the remaining
      acidity in the specimens rendered the pH sufficiently low to prevent the
      subsequent alizarin red staining of the bones. These findings indicate that the
      mineralizing bones at the early stages of development are labile to acidity and
      become decalcified more substantially during the staining process than previously
      appreciated. The following points are important for visualizing such labile
      mineralizing bones in chick embryos: 1) fixing with formaldehyde followed by
      soaking in 70% ethanol, 2) minimizing the time that the specimens are exposed to
      the acidic Alcian blue solution, and 3) neutralizing and dehydrating the
      specimens by an alkaline-alcohol solution immediately after the cartilage
      staining. When the exact onset and/or an early phase of ossification are of
      interest, the current double-staining procedure should be accompanied by a
      control single-staining procedure directed only toward bone.

PMID- 20701552
TI  - Raltegravir: a review of its pharmacokinetics, pharmacology and clinical studies.
AB  - IMPORTANCE OF THE FIELD: Raltegravir is the first HIV-integrase inhibitor
      licensed by the FDA. AREAS COVERED IN THIS REVIEW: A PubMed search was conducted
      for all published reports up to 1 May 2010 related to raltegravir
      pharmacokinetics, pharmacology, drug-drug interactions and clinical studies in
      HIV-infected patients. Also included in this review are the updated European and
      US Prescriber's Information (European Medicines Agency and the FDA) and abstracts
      from recent international scientific meetings. WHAT THE READER WILL GAIN: After
      reading the review, a thorough insight in raltegravir pharmacokinetics and
      pharmacology will be obtained, as well as an up-to-date overview of all published
      drug-drug interaction studies. Furthermore, one should be able to make an
      evidence-based opinion on the drug's clinical efficacy and tolerability. TAKE
      HOME MESSAGE: Raltegravir is a welcome addition to the antiretroviral drug
      armamentarium due to its good tolerability, low potential for drug-drug
      interactions and good clinical efficacy in both treatment-naive and -experienced
      patients.

PMID- 20701553
TI  - Effects of herbal products on the metabolism and transport of anticancer agents.
AB  - IMPORTANCE OF THE FIELD: Cancer patients on chemotherapy treatment often seek
      herbal therapies and this may alter the clearance of anticancer drugs. AREAS
      COVERED IN THIS REVIEW: Many anticancer drugs are metabolized by CYPs and are
      substrates of P-glycoprotein, breast cancer resistance protein and multi-drug
      resistance proteins. CYPs and drug transporters are subject to inhibition and/or
      induction by the herbal medicines used by cancer patients and the metabolism and
      pharmacokinetics of anticancer agents may be altered by herbal products. There
      are increased reports on the interaction of herbal medicines with anticancer
      agents. A clinical study in cancer patients reported that treatment of St John's
      wort at 900 mg/day orally for 18 days decreased the plasma levels of the active
      metabolite of irinotecan, SN-38, by 42%. In healthy subjects, treatment with St
      John's wort for 2 weeks significantly decreased the systemic exposure of imatinib
      by 32%. Induction and/or inhibition of CYPs and transporters is considered an
      important mechanism for these interactions. WHAT THE READER WILL GAIN: Potential
      interactions of herbal medicines with anticancer agents have become a safety
      concern in cancer chemotherapy. TAKE HOME MESSAGE: Further studies are warranted
      to investigate the efficacy and safety profiles of herbal medicines commonly used
      by cancer patients.

PMID- 20701554
TI  - Advances in chemotherapy in advanced non-small-cell lung cancer.
AB  - IMPORTANCE OF THE FIELD: Lung cancer is the most common cancer in the world
      today, in terms of both incidence and mortality. Non-small-cell lung cancer
      (NSCLC) accounts for about 85% of all lung cancers diagnosis, and the majority of
      people diagnosed with NSCLC have advanced disease. AREAS COVERED IN THIS REVIEW:
      In this review the main advances achieved in the medical treatment of advanced
      NSCLC are discussed, regarding both targeted therapies and chemotherapy. Among
      targeted therapies, recent data on the anti-vascular endothelial growth factor
      (VEGF) monoclonal antibody bevacizumab and the epidermal growth factor receptor
      tyrosyne kinase inhibitors (EGFR-TKIs) gefitinib and erlotinib are described.
      Among chemotherapeutic agents, the role of pemetrexed is discussed. WHAT THE
      READER WILL GAIN: The reader will gain up-to-date information on the main
      advances, achieved in the last 3 years in the medical treatment of advanced
      NSCLC. TAKE HOME MESSAGE: Some recent advances have changed the face of the first
      line chemotherapy of advanced NSCLC, giving physicians more options to tailor
      choice in this challenging setting.

PMID- 20701555
TI  - Everolimus: efficacy and safety in cardiac transplantation.
AB  - IMPORTANCE OF THE FIELD: Prognosis after cardiac transplantation continues to
      improve with long-term outcomes limited by malignancy and coronary allograft
      vasculopathy (CAV). Everolimus may potentially reduce these late term
      complications, while maintaining the low cellular rejection rates seen with
      standard therapy. AREAS COVERED IN THIS REVIEW: Multiple studies have
      demonstrated the efficacy of everolimus in reducing acute rejection in heart
      transplant patients, progression and development of CAV, and the prevention and
      treatment of common malignancies, including skin cancer and Kaposi sarcoma. This
      review re-examines these studies with a focus on patient tolerability and safety.
      WHAT THE READER WILL GAIN: Tolerability and safety of everolimus remain a concern
      with pneumonitis, effusions, mouth ulcers, edema and impaired wound healing
      associated with morbidity and mortality. Studies have repeatedly demonstrated
      renal function deterioration with concomitant everolimus and a standard dose
      calcineurin inhibitor (CNI). This impact can be partly reduced with CNI dose
      reduction without an increase in the rate of rejection. TAKE HOME MESSAGE: If
      future studies confirm reduced CAV and malignancy rates, everolimus will become
      an important agent in de novo and maintenance immunotherapy in cardiac
      transplantation. Patient centered immunotherapy is preferred to protocol-based
      immunotherapy as it allows tailoring of immune therapy to each individual
      patient's rejection risk and side profile.

PMID- 20701556
TI  - Health promotion and secondary prevention: response to Milat, O'Hara and Develin.
AB  - This paper responds to a recent HPJA article by Milat, O'Hara and Develin, which
      called for health promotion practitioners to be more closely involved in
      secondary prevention of Type 2 diabetes. It considers the resources currently
      available to health promotion in Australia, and examines and critiques the
      terminology of prevention used by Milat et al. The paper argues that Milat et al.
      give insufficient attention to the central role of social determinants of health
      in preventing Type 2 diabetes and in reducing health inequalities in the
      population. The paper agrees that increased health promotion involvement in Type
      2 diabetes prevention programs may be beneficial, but argues that funds for such
      programs should come from the services that run them, not from the tiny health
      promotion budget. Given the current and projected scale of Type 2 diabetes in
      Australia, there is value in applying the concept of 'moving upstream' to this
      health issue. The paper concludes that, given current resources, the best use of
      Australia's specialist health promotion workforce is in 'upstream' programs that
      can benefit the whole population as well as those at risk of Type 2 diabetes.

PMID- 20701557
TI  - Playgroups as a setting for nutrition and physical activity interventions for
      mothers with young children: exploratory qualitative findings.
AB  - ISSUE ADDRESSED: The child bearing years are associated with increased risk of
      weight gain for many women. Little is known about the attitudes and preferences
      for nutrition and physical activity interventions in this population. This
      research investigated the barriers and facilitators of mothers with young
      children to engage in healthy physical activity and nutrition behaviours.
      METHODS: Eight focus groups were conducted with mothers (n = 65) who attended
      Perth, metropolitan playgroups. Transcriptions from the groups plus observer
      notes were used to conduct a thematic analysis. RESULTS: Participants were aware
      of the need for good nutrition and adequate physical activity but many failed to
      meet public health recommendations. Many participants were keen to improve their
      diet and increase their levels of physical activity. However, a major barrier to
      adopting and maintaining healthy diets and adequate physical activity levels was
      a shift in priorities from investing in their own health to investing in their
      children's. CONCLUSIONS: Interventions using a 'whole family' approach are more
      likely to be successful in engaging mothers. Interventions should focus on
      strengthening mothers' self efficacy surrounding eating and physical activity.

PMID- 20701558
TI  - Second hand smoke in alfresco areas.
AB  - ISSUE ADDRESSED: There are moves to ban smoking in outdoor areas of pubs,
      restaurants and cafes. Some argue that this is unnecessary as exposure to second
      hand smoke (SHS) is minimal. The aim of this study was to determine potential
      exposure of patrons to SHS in outdoor areas of eating and drinking venues.
      METHODS: Concentrations of fine particulate matter (PM2.5) were measured in the
      alfresco areas of 28 cafes and pubs. Data were collected on the number of smokers
      present during sampling and factors that could influence PM2.5concentrations.
      PM2.5concentrations for periods with and without smokers were compared using
      paired and independent sample tests. RESULTS: PM2.5 concentrations were
      significantly increased when there was at least one smoker compared to periods
      with no smoking (14.25 microg/m3 and 3.98 g/m3, respectively). There was evidence
      of a dose response increase with mean concentrations for none, one and two or
      more smokers of 3.98, 10.59and 17.00microg/m3, respectively. The differences
      remained significant after controlling for other factors. When two or more people
      were smoking, average PM2.5reached levels the US Environmental Protection Agency
      warns may put particularly sensitive people at risk of respiratory symptoms.
      CONCLUSIONS: Smoking increases PM2.5concentrations in outdoor areas to levels
      that are potentially hazardous to health.

PMID- 20701559
TI  - Applying a Health Promoting Schools approach to nutrition interventions in
      schools: key factors for success.
AB  - ISSUE ADDRESSED: To assess the effectiveness of using a Health Promoting Schools
      (HPS) framework to deliver a nutrition intervention in schools. METHODS: 'CREATE
      healthy eating in schools' used a HPS framework to assist key school health
      stakeholders to increase healthier food and drink choices across 68 schools in
      South Australia. Data were collected on a range of measures including workshop
      feedback, resource evaluation, canteen menu assessments and case studies.
      RESULTS: Twenty-nine workshops were provided across 10 metropolitan and rural
      locations. Overall, 254 participants from 60 schools attended workshops, with an
      average of three people from each school. An average of 90% of all respondents
      found workshops useful/very useful, with most participants reporting they had
      increased knowledge and skills of healthy eating, healthy eating guidelines and
      menu planning at the end of workshops. At the completion of the program, many
      participants reported increasing healthy food choices across the school. Menu
      assessments of a small selection of participating school menus (n=10) supported
      these findings, with the majority of menus (n=9) showing increases in healthy
      food choices from 2005 to 2006. CONCLUSIONS: Implementation of the 'CREATE
      healthy eating in schools' program resulted in self-reported improvements in
      healthy eating activities and increases in healthy food choices in a number of
      schools.

PMID- 20701560
TI  - Evaluation of the 2008 NSW water campaign.
AB  - ISSUE ADDRESSED: The consumption of soft and other sweetened drinks is an
      emerging nutrition issue in Australia. In 2005-6, 63% of NSW children aged
      between 2 and 15 years consumed sweetened drinks (soft drinks, cordials or sports
      drinks) weekly, 33% of which consumed at least 6 cups per week. In 2008 NSW
      Health implemented the 'Water Campaign' to increase the proportion of NSW
      children up to 15 years of age who consume water in place of sweetened drinks.
      METHODS: A pre-post survey study design was used to evaluate the Campaign. Two
      telephone surveys of stratified random samples of 500 respondents each from the
      primary target audience (parents and carers of children up to 15 years of age)
      were conducted across NSW. RESULTS: Fifty-three per cent of respondents in the
      post-survey said that they recalled the mass media Campaign when it was described
      to them compared to 19% in the pre-survey. There was an increase in parents'
      knowledge of the high sugar content of sweetened drinks and a decline in the
      reported consumption of sweetened drinks by boys. CONCLUSIONS: Though modest in
      size and duration, the campaign was successful in achieving a number of campaign
      objectives, particularly changes in parent's and carer's knowledge and awareness
      of water related nutrition and reduced reported consumption of sweetened drinks
      among boys.

PMID- 20701561
TI  - Fear and shame: using theatre to destigmatise mental illness in an Australian
      Macedonian community.
AB  - ISSUES ADDRESSED: Previous research has revealed low levels of mental health
      service utilisation and widespread discrimination towards people with mental
      illness in Sydney's Macedonian community. As an extension to a multifaceted
      community intervention to improve mental health literacy and reduce stigma, a
      Macedonian-language play was produced. METHODS: Qualitative data from earlier
      studies and professional experience were used to craft a script that was
      performed by actors from the Macedonian community. Eight performances at three
      venues were attended by approximately 1,600 people. Telephone interviews with 236
      audience members (including 76 with personal or family experience of mental
      illness) and 25 key informants were conducted 1-10 months later. Data were
      analysed and compared with data collected pre-intervention. RESULTS: Compared
      with the earlier data, the audience sample was significantly more likely to
      report positive community attitudes toward people with mental illness and their
      families, and to favour disclosure to extended family and friends. They also
      indicated greater willingness to seek help from health services. Key informants
      reported greater service utilisation since the play was staged. CONCLUSIONS:
      Building on previous work, theatre was an effective means of disseminating
      information and reducing stigma around mental illness in the target community.

PMID- 20701562
TI  - Knowledge and perceptions of cervical cancer and healthcare in Vanuatu.
AB  - ISSUE ADDRESSED: There is increasing evidence of unacceptably high levels of
      cervical cancer abnormalities in Vanuatu. The purpose of this research was to
      determine cervical health awareness in local women from rural and urban
      environments. METHODS: Women from hospitals, health clinics and small local
      villages were invited to participate in a health survey. This investigated health
      knowledge, current information sources and perceived limitations in accessing
      health information. RESULTS: A total of 422 surveys were undertaken, a response
      rate of 93% in urban centres and 95% in rural areas. There was a direct
      relationship between the number of school years completed and awareness of
      cancer. Nurses, doctors and village health workers all played a vital role in
      providing women's health care information. General embarrassment and a lack of
      knowledge were the greatest limitations reported to affect the ability and
      confidence for women to investigate health concerns. CONCLUSIONS: Vanuatu women
      are poorly educated regarding health issues, particularly cervical cancer.
      Strategies to improve cervical cancer awareness may include travelling workshops,
      an active media campaign and the introduction of culturally sensitive education
      programs tailored to formal and non-formal environments. Programs should inform
      whole communities and health care professionals.

PMID- 20701563
TI  - Beliefs, barriers, social support, and environmental influences related to
      diabetes risk behaviours among women with a history of gestational diabetes.
AB  - ISSUE ADDRESSED: Women with previous gestational diabetes mellitus (GDM) are at
      increased risk of developing type 2 diabetes; this risk is higher in non
      Caucasian women. This study explored the beliefs, attitudes, social support,
      environmental influences and other factors related to diabetes risk behaviours
      among Arabic, Cantonese/Mandarin, and English speaking women with recent GDM.
      METHODS: Women living in the Sydney metropolitan area (Australia) who had GDM 6
      36 months previously were included. In-depth semi-structured telephone interviews
      on women's experiences and perceptions of GDM and the lifestyle risk factors for
      developing type 2 diabetes were conducted in the language participants spoke at
      home (n=20 Arabic, 20 Cantonese/Mandarin, 17 English). Data were analysed for
      underlying themes using NVivo software. RESULTS: Mental distress, role
      perceptions, social support and cultural expectations were major issues related
      to women's struggles to find the right balance between the large proportion of
      household and child care responsibilities and leading a healthy lifestyle.
      CONCLUSION: Women's ability to follow a healthy lifestyle is embedded in their
      psychological wellbeing and the social and cultural context of their lives. The
      study highlights the need for a holistic approach that ensures personal support
      and access to services as well as lifestyle specific programs.

PMID- 20701564
TI  - The Australian Grey Nomads--are they who we think they are? Enhancing formative
      research through the quantitative assessment of psychological constructs.
AB  - ISSUE ADDRESSED: Measures of 'social identity' and 'psychological sense of
      community' were included within a broader formative research inquiry to gain
      insight into the identity characteristics and level of connectedness among older
      recreational road travellers (commonly known as Grey Nomads). The research sought
      to gain insights on how best to reach or speak to this growing driver cohort.
      METHOD: Participants included 631 older recreational road travellers ranging in
      age from 50 years to over 80 years. Data were obtained through three scales which
      were incorporated into a larger formative research survey; an identity hierarchy,
      the Three Factor Model of Social Identity and the Sense of Community Index.
      RESULTS: Older recreational road travellers see themselves principally as
      couples, with social group identity being secondary. Although many identified to
      some degree with the Grey Nomad identity, when asked to self categorise as either
      members of the Broad Network of Recreational Vehicle Travellers or as Grey
      Nomads, the majority categorised themselves as the former. Those identifying as
      Grey Nomads, however, reported significantly higher levels of 'social
      identification' and 'sense of community'. CONCLUSION: The Grey Nomad identity may
      not be the best identity at which to target road safety messages for this cohort.
      Targeting travelling 'couples' may be more efficacious. Using the 'Grey Nomad'
      identity is likely to reap at least some success, however, given that many
      identified to some degree with this group identity. Those identifying as Grey
      Nomads may be more open to community participation or behaviour change given
      their significantly higher levels of 'social identity' and 'sense of community'.

PMID- 20701565
TI  - The role of a community kitchen for clients in a socio-economically disadvantaged
      neighbourhood.
AB  - ISSUE ADDRESSED: To investigate the role of a community kitchen for clients
      living in a socio-economically disadvantaged neighbourhood. METHODS: In 2005,
      semi-structured interviews were conducted with 21 clients attending a community
      kitchen located in a socio-economically disadvantaged neighbourhood in New South
      Wales. Participants were asked their reasons for attending the kitchen.
      Qualitative content analysis was used to categorise verbatim responses to the
      open-ended questions. RESULTS: The main reasons participants attended the
      community kitchen were to alleviate food insecurity and the opportunity to
      interact socially in a safe place, followed by obtaining advice on a broad range
      of services to address health and social problems. CONCLUSIONS: The community
      kitchen had a positive effect on the lives of socially isolated people who are
      usually hard to reach, by providing meals, and facilitating social interaction
      and access to a wide range of services.

PMID- 20701566
TI  - Sun-protective behaviours of beach goers in the North-West.
AB  - ISSUE ADDRESSED: The study investigates the sun-protective behaviours of beach
      goers in the north-west of Western Australia as the basis for a new health
      promotion intervention to be implemented in the area. METHODS: A cross-sectional,
      observational survey of 1,498 beach goers in 25 beach locations across northwest
      Western Australia. Details of sun-protective clothing (none, hat with no shirt,
      shirt with no hat and full coverage) were recorded, as was time on beach, age and
      gender. Environmental audits were also completed to characterise the effects of
      the natural and built environments on sun-protective behaviours. RESULTS: Both
      females and children had the lowest rates of sun protection - 33.7% of females
      were found to wear shirts with no hats, compared to 29.0% of males, and they were
      less likely to be fully covered than males (30.3% compared to 41.5%). Children
      were more likely to wear shirts with no hats (43.1%) compared to adults (28.2%).
      CONCLUSIONS: Female and child beach goers represent two groups that are at a
      higher risk of developing skin cancer and, therefore, should become targets for a
      sustainable, effective and multi-component health promotion program.

PMID- 20701567
TI  - Traditional Indigenous Games promoting physical activity and cultural
      connectedness in primary schools--cluster randomised control trial.
AB  - ISSUE ADDRESSED: This study investigated the effectiveness of Traditional
      Indigenous Games (TIG) to improve physical activity and cultural connectedness
      among primary school students in the community renewal areas of Townsville in
      North Queensland. METHODS: A cluster randomised control trial was conducted in
      four primary schools in 2007. Baseline and post implementation surveys were
      conducted in two intervention and two control schools and the results were
      compared. RESULTS: TIG delivered in primary schools every week over period of
      three months did not contribute to any statistically significant improvement in
      intervention and control groups in physical activity levels or cultural
      connectedness. CONCLUSIONS: Further research specifically in terms of intensity
      and duration of TIG may inform whether physical activity may be improved.
      Enhancing the Indigenous cultural features of the existing TIG kit might
      positively influence Indigenous cultural connectedness.

PMID- 20701568
TI  - Twenty years of your national health promotion association.

PMID- 20701569
TI  - Opisthorchiidosis--a review.
AB  - The discovery history of opisthorchiid flukes dates back more than 200 years. The
      life cycle of these liver flukes includes prosobranch snails as the first and a
      big variety of freshwater fish as the second intermediate hosts. Opisthorchis
      felineus, O. viverrini and Clonorchis sinensis are species of major medical
      importance, while sporadic cases of human infection with other representatives of
      this family are also documented in the literature. There are estimations that 17
      million people are infected and more than 350 million people are at risk, mainly
      in Asian countries. Although opisthorchiid flukes live in the bile ducts of the
      liver and in the gall bladder, they can affect surrounding liver tissue and even
      other organs. They are also known to induce the production of autoantibodies as
      well as allergic reactions. However, the main medical significance is their role
      in the formation of malignant tumors. Since the clinical symptoms are not
      specific, a diagnosis must be confirmed by parasitological examination or the
      detection of antibodies. Apart from coproscopical methods, there are more recent
      and highly specific assays available, like the detection of coproantigen or the
      detection of DNA. Praziquantel is the drug of choice for the treatment of
      opisthorchiidosis. In order to prevent infection, consumption of raw flesh of
      freshwater fish must be avoided.

PMID- 20701570
TI  - Drug target in eosinophilic meningitis caused by Angiostrongylus cantonensis.
AB  - Eosinophilic meningitis caused by Angiostrongylus cantonensis is an emerging
      infectious disease. It is the most common form of human angiostrongyliasis. The
      diagnosis is made by clinical criteria including the presence of cerebrospinal
      fluid eosinophils and a history of exposure to A. cantonensis larvae, e.g., from
      raw freshwater snails or contaminated vegetables. Among various treatment
      options, corticosteroid is the only effective treatment.

PMID- 20701571
TI  - The Digenea parasite Opisthorchis felineus: a target for the discovery and
      development of novel drugs.
AB  - Opisthorchosis is a helminthiasis affecting mainly the hepatobiliary system and
      pancreas; its most dramatic complication is malignization of the organs infected
      by the parasites. The causative agents of opisthorchosis are two species of liver
      flukes, the trematodes belonging to the family Opisthorchiidae--Opisthorchis
      felineus and O. viverrini. The Chinese liver fluke, Clonorchis sinensis, also
      member of the family Opisthorchiidae, causes clonorchosis, a disease very close
      in symptomatology. According to different estimations, up to 40 million people
      are currently infected with these liver flukes and up to 600-750 million people
      in Eurasian countries constitute the risk group. These parasites colonize ever
      increasing new areas in Eurasia where this disease has never been previously
      reported. Opisthorchiases are gradually transforming from a local problem of
      individual geographic regions to a widespead problem; in particular, O. viverrini
      is now referred to as "an underestimated parasite." As we see it, O. felineus has
      all the reasons to share this status. First and foremost, the observed expansion
      is likely to be connected with the ever-increasing intensity of traffic flows and
      migration of the infection carriers between cities, regions, and countries. This
      review briefs the characteristics of O. felineus and the other liver flukes
      persisting in various countries of Eurasia, clinical manifestations of
      opisthorchosis, the drugs for chemotherapy of trematodiasis, and the strategy for
      discovery of new antihelminthic drugs.

PMID- 20701572
TI  - Trichinella spiralis: genomic application to control a zoonotic nematode.
AB  - The nematode Trichinella spiralis and related species are zoonotic food-borne
      pathogens of humans. The muscle larval stage of this parasite establishes a
      chronic infection in skeletal muscle cells of humans who acquire trichinellosis.
      Muscle larvae also reside in skeletal muscles of animals, swine in particular,
      and other food animals, including game animals. These muscle larvae are the
      source of zoonotic transmission to humans. Once established, muscle larvae become
      less susceptible to anthelmintics that are effective against other stages of the
      parasite. Very little information exists to guide discovery of new drug targets
      and improved methods of eliminating muscle larvae established in muscle cells of
      humans or food animals. Here we discuss progress that has been made on sequencing
      the genome of T. spiralis. This informational resource should prove valuable for
      dissecting molecular characteristics of this parasite that warrant investigation
      as targets for chemotherapy. The availability of the T. spiralis genome has made
      possible the comparison of genomes from nematodes that span the evolutionary
      extremes of the phylum Nematoda. We describe a pan-phylum comparison of genomes
      that is underway. This comparative genomics approach is expected to identify
      molecular characteristics that are conserved among all nematodes, and hence
      applicable to nematode pathogens throughout the phylum, including species from
      the genus Trichinella. T. spiralis expression data for muscle larvae has been
      integrated with genome sequences to identify specific genes and proteins with
      relevance to control of this stage of the parasite. Examples are discussed in
      which genomic information may advance understanding of T. spiralis biology and
      new methods for treating infections by this parasite.

PMID- 20701573
TI  - Cyclospora cayetanensis: a review, focusing on some of the remaining questions
      about cyclosporiasis.
AB  - Cyclosporiasis is a protracted, relapsing gastroenteritis and has a short
      recorded history. Cyclospora cayetanensis is an enigmatic parasite since its
      discovery highlights the need for isolation of cases of infection that could be
      part of widespread outbreaks. It is associated with diarrhoea among children in
      developing countries in the Americas, where C. cayetanensis is endemic;
      traveller's diarrhoea and/or food and waterborne outbreaks sometimes occur in the
      developed countries. In SubSaharan Africa and Egypt, cyclosporiasis has been
      reported to occur in both immunocompromised and immunocompetent patients.
      Zoonotic species of Cyclospora have also been identified worldwide in primates,
      indicating likely endemicity of this underreported disease. This can be
      attributed to the lack of awareness in the public and medical profession
      concerning the disease, which is, therefore, not routinely tested at the health
      centres. The correlation between the density of water contamination and the
      prevalence of cyclosporiasis among the individuals of each area is significant.
      No doubt, water is the main vehicle of transmission in the present community.
      Soil contact and poultry are significant risk factors. All literature on C.
      cayetanensis, cyclosporiasis worldwide, and endemic cyclosporiasis was searched
      from libraries, colleagues and internet. Although cyclosporiasis is considered an
      enigma worth unravelling, with many aspects of this disease and its transmission
      having been uncovered only recently, the situation has been rapidly changing
      since the disease first came to medical attention in the 1970s.

PMID- 20701574
TI  - Ascaris lumbricoides: an overview of therapeutic targets.
AB  - A. lumbricoides is the largest of the common nematode parasites of man and has
      been associated with intestinal pathology, respiratory symptoms and malnutrition
      in children from endemic areas. Current anthelmintic treatments have proven to be
      safe. However, a reduced efficacy of single dose drugs has been reported. In
      veterinary practice, anthelmintic drug resistance is an irreversible problem.
      Thus, research and development of sensitive tools for early detection of drug
      resistance as well as new anthelmintic approaches are urgently needed. In this
      review, we summarized data providing information about current drug therapy
      against A. lumbricoides and other intestinal helminths, new drugs in experimental
      trials, future drugs perspectives and the identification of immunogenic parasite
      molecules that may be suitable vaccine targets. In addition to the WHO
      recommended drugs (albendazole, mebendazole, levamisole, and pyrantel pamoate),
      new anthelmintic alternatives such as tribendimidine and Nitazoxanide have proved
      to be safe and effective against A. lumbricoides and other soil-transmitted
      helminthiases in human trials. Also, some new drugs for veterinary use,
      monepantel and cyclooctadepsipeptides (e.g., PF1022A), will probably expand
      future drug spectrum for human treatments. The development of genomic technology
      has provided a great amount of available nematode DNA sequences, coupled with new
      gene function data that may lead to the identification of new drug targets
      through efficient mining of nematode genomic databases. On the other hand, the
      identification of nematode antigens involved in different parasite vital
      functions as well as immunomodulatory molecules in animals and humans may
      contribute to future studies of new therapeutic approaches.

PMID- 20701575
TI  - Giardiasis: the ever-present threat of a neglected disease.
AB  - Although giardiasis has been a threat to mankind for thousands of years, this
      protozoan infection was, until recently, relatively neglected. Giardia duodenalis
      is recognised as a major cause of parasite-induced diarrhoea in humans and
      animals, and is currently an important public health problem, placing a heavy
      burden on both diagnostic and treatment services at health care institutions,
      mostly in developing countries, but also in highly developed countries. Steady
      progress in recent years, using a combination of molecular, immunological, and
      clinical approaches, has substantially increased our understanding of Giardia and
      important aspects of the clinical manifestations that it causes. The purpose of
      this review is to provide an overview of the extent of Giardia infection, the
      implications of water and food in Giardia transmission, new aspects regarding
      clinical diagnosis and environmental detection, treatment, and some approaches
      towards prevention and control. A number of future research priorities are also
      presented.

PMID- 20701576
TI  - A glance at Taenia saginata infection, diagnosis, vaccine, biological control and
      treatment.
AB  - The Taenia saginata taeniasis-cysticercosis complex is a cosmopolitan zoonosis of
      great medical, veterinary and economic importance where humans play an important
      role as the carrier of adult stage and cattle as carrier of the larval stage of
      the parasite. Here we reviewed aspects concerning diagnosis, vaccine development,
      biological control and treatment of the disease.

PMID- 20701584
TI  - Disturbance of inorganic phosphate metabolism in diabetes mellitus: its impact on
      the development of diabetic late complications.
AB  - The pathogenesis of diabetic late complications (DLC) is multifactorial. Studies
      of mechanisms leading to early functional microvascular changes in retina and
      kidneys point towards a disturbance in the metabolism of inorganic phosphate (Pi)
      in diabetes. Since tissue hypoxia and reduced high energy phosphates may be
      important factors in the development of DLC, the influence of Pi concentration on
      the metabolism and function of the erythrocytes and renal tubular cells, as well
      as the relationship of the concentration of Pi to total oxygen consumption, have
      been reviewed. While extensive research data in non-diabetic conditions support
      the suggestion, that the Pi concentration is a determining factor in regulation
      of metabolism and rate of oxygen consumption, diabetes shows the opposite
      behavior. In diabetes, the highest oxygen consumption is associated with the
      lowest concentration of Pi. Many conventionally-treated juvenile diabetic
      patients respond as if their tissues were in a state of chronic hypoxia. A
      disturbance in phosphate handling occurs in the kidney tubules, where the
      excessive sodium-dependent glucose entry in diabetics depolarizes the
      electrochemical sodium gradient and consequently impairs inorganic phosphate
      reabsorption. Similar changes may occur in other cells and tissues in which
      glucose entry is not controlled by insulin, and particularly in poorly-regulated
      diabetic patients in whom long-term vascular complications are more likely.

PMID- 20701585
TI  - Interrelationships between hepatic fat and insulin resistance in non-alcoholic
      fatty liver disease.
AB  - Non-alcoholic fatty liver disease (NAFLD) is strongly associated with insulin
      resistance, and its prevalence is rising in parallel with worldwide increases in
      obesity and type 2 diabetes. However, the nature of this relationship remains
      debatable. In particular, it is unclear whether insulin resistance causes NAFLD
      or hepatic steatosis per se reduces insulin sensitivity. This review will examine
      data from recent studies on the link between insulin resistance and NAFLD,
      focusing on studies that have attempted to dissociate fatty liver and hepatic
      insulin resistance.

PMID- 20701586
TI  - Shoulder manifestations of diabetes mellitus.
AB  - The musculoskeletal system can be affected by diabetes in a number of ways. The
      shoulder is one of the frequently affected sites. One of the rheumatic conditions
      caused by diabetes is frozen shoulder (adhesive capsulitis), which is
      characterized by pain and severe limited active and passive range of motion of
      the glenohumeral joint, particularly external rotation. This disorder has a
      clinical diagnosis and the treatment is based on physiotherapy, non-steroidal
      anti-inflammatory drugs (NSAIDs), corticosteroid injections and, in refractory
      cases, surgical resolution. As with adhesive capsulitis, calcific periarthritis
      of the shoulder causes pain and limited joint mobility, although usually it has a
      better prognosis than frozen shoulder. Reflex sympathetic dystrophy, also known
      as shoulder-hand syndrome, is a painful syndrome associated with vasomotor and
      sudomotor changes in the affected member. Diabetic amyotrophy usually affects the
      peripheral nerves of lower limbs. However, when symptoms involve the shoulder
      girdle, it must be considered in the differential diagnosis of shoulder painful
      conditions. Osteoarthritis is the most common rheumatic condition. There are many
      risk factors for shoulder osteoarthritis including age, genetics, sex, weight,
      joint infection, history of shoulder dislocation, and previous injury, in older
      age patients, diabetes is a risk factor for shoulder OA. Treatment options
      include acetaminophen, NSAIDs, short term opiate, glucosamine and chondroitin.
      Corticosteroid injections and/or injections of hyaluronans could also be
      considered. Patients with continued disabling pain that is not responsive to
      conservative measures may require surgical referral. The present review will
      focus on practice points of view about shoulder manifestations in patients with
      diabetes.

PMID- 20701587
TI  - Application of chromatography technology in the separation of active components
      from nature derived drugs.
AB  - Chromatography technology has been widely applied in various aspects of the
      pharmacy research on traditional Chinese medicine (TCM). This paper reviews
      literatures, published in the past decades, on the separation of active component
      from TCM using chromatography technology. Ultra-performance liquid chromatography
      (UPLC), high-speed counter-current chromatography (HSCCC), rapid resolution
      liquid chromatography (RRLC), supercritical fluid chromatography (SFC), affinity
      chromatography (AC), and bio-chromatography (BC) are introduced in detail.
      Compared to high performance of high-performance liquid chromatography (HPLC),
      analysis time and solvent loss are significantly reduced by UPLC with increase in
      resolution and sensitivity. Some ingredients from nature derived drugs can be
      separated more completely by HSCCC, which has remarkable characteristics such as
      low cost, simple operation and no pollution. Trace components from complex
      systems can be selectively and efficiently separated and purified by AC, This
      feature makes it effective in isolation and identification of active components
      of Chinese herbs. Interference of some impurities could be excluded by BC. Active
      ingredients that are difficult to be separated by normal method can be acquired
      by SFC. Currently, application of novel chromatography techniques in TCM is still
      in the exploratory stage and many problems, such as preparation of stationary
      phase and detection, need to be solved.

PMID- 20701588
TI  - HDAC inhibitors - new generation of target specific treatment.
AB  - Histone Deacetylases (HDACs) enzymes are critical in regulating gene expression
      and transcription. They also play a fundamental role in regulating cellular
      activities such as cell proliferation, survival and differentiation. Inhibition
      of HDACs has generated many fascinating results including a new strategy in human
      cancer therapy. HDAC Inhibitors (HDACIs) like SAHA, TSA are emerging as new
      promising drugs for various anti-inflammatory and CNS-disorders. This review,
      along with chemical classification, emphasizes on the therapeutic potential of
      various HDACIs against different diseases.

PMID- 20701589
TI  - Contraction regulates site-specific phosphorylation of TBC1D1 in skeletal muscle.
AB  - TBC1D1 (tre-2/USP6, BUB2, cdc16 domain family member 1) is a Rab-GAP (GTPase
      activating protein) that is highly expressed in skeletal muscle, but little is
      known about TBC1D1 regulation and function. We studied TBC1D1 phosphorylation on
      three predicted AMPK (AMP-activated protein kinase) phosphorylation sites
      (Ser231, Ser660 and Ser700) and one predicted Akt phosphorylation site (Thr590)
      in control mice, AMPKalpha2 inactive transgenic mice (AMPKalpha2i TG) and Akt2
      knockout mice (Akt2 KO). Muscle contraction significantly increased TBC1D1
      phosphorylation on Ser231 and Ser660, tended to increase Ser700 phosphorylation,
      but had no effect on Thr590. AICAR (5-aminoimidazole-4-carboxyamide
      ribonucleoside) also increased phosphorylation on Ser231, Ser660 and Ser700, but
      not Thr590, whereas insulin only increased Thr590 phosphorylation. Basal and
      contraction-stimulated TBC1D1 Ser231, Ser660 and Ser700 phosphorylation were
      greatly reduced in AMPKalpha2i TG mice, although contraction still elicited a
      small increase in phosphorylation. Akt2 KO mice had blunted insulin-stimulated
      TBC1D1 Thr590 phosphorylation. Contraction-stimulated TBC1D1 Ser231 and Ser660
      phosphorylation were normal in high-fat-fed mice. Glucose uptake in vivo was
      significantly decreased in tibialis anterior muscles overexpressing TBC1D1
      mutated on four predicted AMPK phosphorylation sites. In conclusion, contraction
      causes site-specific phosphorylation of TBC1D1 in skeletal muscle, and TBC1D1
      phosphorylation on AMPK sites regulates contraction-stimulated glucose uptake.
      AMPK and Akt regulate TBC1D1 phosphorylation, but there must be additional
      upstream kinases that mediate TBC1D1 phosphorylation in skeletal muscle.

PMID- 20701591
TI  - An inexpensive and portable microvolumeter for rapid evaluation of biological
      samples.
AB  - We describe an improved microvolumeter (MVM) for rapidly measuring volumes of
      small biological samples, including live zooplankton, embryos, and small animals
      and organs. Portability and low cost make this instrument suitable for widespread
      use, including at remote field sites. Beginning with Archimedes' principle, which
      states that immersing an arbitrarily shaped sample in a fluid-filled container
      displaces an equivalent volume, we identified procedures that maximize
      measurement accuracy and repeatability across a broad range of absolute volumes.
      Crucial steps include matching the overall configuration to the size of the
      sample, using reflected light to monitor fluid levels precisely, and accounting
      for evaporation during measurements. The resulting precision is at least 100
      times higher than in previous displacement-based methods. Volumes are obtained
      much faster than by traditional histological or confocal methods and without
      shrinkage artifacts due to fixation or dehydration. Calibrations using volume
      standards confirmed accurate measurements of volumes as small as 0.06 microL. We
      validated the feasibility of evaluating soft-tissue samples by comparing volumes
      of freshly dissected ant brains measured with the MVM and by confocal
      reconstruction.

PMID- 20701590
TI  - Mass spectrometry-based metabolomics, analysis of metabolite-protein
      interactions, and imaging.
AB  - Our understanding of biology has been greatly improved through recent
      developments in mass spectrometry, which is providing detailed information on
      protein and metabolite composition as well as protein-metabolite interactions.
      The high sensitivity and resolution of mass spectrometry achieved with liquid or
      gas chromatography allows for detection and quantification of hundreds to
      thousands of molecules in a single measurement. Where homogenization-based sample
      preparation and extraction methods result in a loss of spatial information, mass
      spectrometry imaging technologies provide the in situ distribution profiles of
      metabolites and proteins within tissues. Mass spectrometry-based analysis of
      metabolite abundance, protein-metabolite interactions, and spatial distribution
      of compounds facilitates the high-throughput screening of biochemical reactions,
      the reconstruction of metabolic networks, biomarker discovery, determination of
      tissue compositions, and functional annotation of both proteins and metabolites.

PMID- 20701592
TI  - Covalent quantum dot receptor linkage via the acyl carrier protein for single
      molecule tracking, internalization, and trafficking studies.
AB  - Here we describe a labeling technique for the covalent linkage of quantum dots to
      transmembrane receptors for single-molecule tracking. Our method combines the
      acyl carrier protein (ACP) technique with coenzyme A (CoA)-functionalized quantum
      dots to covalently attach quantum dots to ACP fusions of receptor proteins. The
      advantages of this approach include: (i) the use of a smaller attachment linker
      than in many other quantum dot-labeling systems; (ii) the ability to achieve a
      reliable 1:1 fluorophore-to-receptor labeling stoichiometry; (iii) the
      specificity of the method; and (iv) the covalent nature of the quantum dot
      linkage. We demonstrate the general suitability of this technique in single
      molecule tracking, internalization, and trafficking studies by imaging two
      different transmembrane receptors in living cells.

PMID- 20701593
TI  - Modified agarose gel for high-performance Southern blotting of short DNA
      fragments.
AB  - Southern blotting is a common method used for the study of gene organization.
      Current methods of DNA transfer for Southern blotting, however, can be
      inefficient for high concentration agarose gels. Here, we report a method for
      high-performance Southern blotting of short DNA fragments such as nucleosomal
      DNAs by using a discontinuous agarose zone gel. The results show that sharp and
      well-resolved fractionation of short DNA fragments comparable to that from a high
      concentration agarose gel could be obtained using a low-concentration agarose gel
      with a small zone of high-concentration agarose, and that the resulting DNA
      transfer is highly efficient and rapid.

PMID- 20701594
TI  - M-marker 2009, a marker set for mapping medaka mutants using PCR length
      polymorphisms with an automated microchip gel electrophoresis system.
AB  - We have developed a highly effective marker set for assigning medaka mutants to
      specific linkage groups (LG) in bulk segregation analysis by PCR product length
      polymorphisms (PLPs). The marker set permits analysis using an automated
      microchip electrophoresis system as well as conventional agarose gel
      electrophoresis.

PMID- 20701595
TI  - The definition of hypotension affects its incidence.

PMID- 20701596
TI  - Scandinavian clinical practice guidelines on general anaesthesia for emergency
      situations.
AB  - Emergency patients need special considerations and the number and severity of
      complications from general anaesthesia can be higher than during scheduled
      procedures. Guidelines are therefore needed. The Clinical Practice Committee of
      the Scandinavian Society of Anaesthesiology and Intensive Care Medicine appointed
      a working group to develop guidelines based on literature searches to assess
      evidence, and a consensus meeting was held. Consensus opinion was used in the
      many topics where high-grade evidence was unavailable. The recommendations
      include the following: anaesthesia for emergency patients should be given by, or
      under very close supervision by, experienced anaesthesiologists. Problems with
      the airway and the circulation must be anticipated. The risk of aspiration must
      be judged for each patient. Pre-operative gastric emptying is rarely indicated.
      For pre-oxygenation, either tidal volume breathing for 3 min or eight deep
      breaths over 60 s and oxygen flow 10 l/min should be used. Pre-oxygenation in the
      obese patients should be performed in the head-up position. The use of cricoid
      pressure is not considered mandatory, but can be used on individual judgement.
      The hypnotic drug has a minor influence on intubation conditions, and should be
      chosen on other grounds. Ketamine should be considered in haemodynamically
      compromised patients. Opioids may be used to reduce the stress response following
      intubation. For optimal intubation conditions, succinylcholine 1-1.5 mg/kg is
      preferred. Outside the operation room, rapid sequence intubation is also
      considered the safest method. For all patients, precautions to avoid aspiration
      and other complications must also be considered at the end of anaesthesia.

PMID- 20701597
TI  - Twenty-three deaths with gamma-hydroxybutyrate overdose in western Sweden between
      2000 and 2007.
AB  - BACKGROUND: gamma-Hydroxybutyrate (GHB) is a drug of abuse with a status as being
      safe. In spite of a reputation of low toxicity, a huge number of deaths
      associated with this drug have been recorded during recent years in Sweden. It is
      unclear whether coingestion with other drugs or ethanol causes death in GHB
      overdoses or whether GHB itself is the main cause of death. OBJECTIVES: The aim
      of this study was to analyze the cause of death in GHB-related fatalities seen in
      our region. METHODS: All cases of deaths with GHB during the year 2000-2007 in
      the region of western Sweden were studied retrospectively. The cases were
      classified as either GHB poisonings without any, with a minor or a major
      influence of other drugs on the cause of death. RESULTS: Twenty-three cases were
      diagnosed as deaths due to GHB overdose. Ninety-one percent coingested other
      substances. Ninety-one percent of the decedents were male. Age varied between 16
      and 46, with the median age at 25 years. Forty-three percent of the cases were
      classified as GHB poisonings without any or a minor influence of other drugs on
      the cause of death. Thirty percent also ingested ethanol. Two patients (9%) were
      only intoxicated with GHB. CONCLUSIONS: Intoxication with GHB carries some
      mortality. Combining GHB with ethanol does not explain the many deaths in our
      region, nor do extremely high plasma concentrations of GHB. The intake of opioids
      increases the toxicity of GHB. The drug itself has such biological activities
      that an overdose is dangerous and may lead to death.

PMID- 20701598
TI  - Nerve perforation with pencil point or short bevelled needles: histological
      outcome.
AB  - BACKGROUND: In the case of needle nerve contact during peripheral blocks, pencil
      point needles are considered less traumatic compared with bevelled needles.
      However, there are not enough data to prove this notion. Therefore, the aim of
      this study was to challenge the hypothesis that nerve perforation with short
      bevelled needles is associated with major nerve damage compared with pencil point
      needles. METHODS: In five anaesthetised pigs, the brachial plexus was exposed
      bilaterally. Up to eight nerves underwent needle nerve perforation using a pencil
      point needles cannula or an short bevelled needle. After 48 h, the nerves were
      resected. The specimens were processed for visual examination and the detection
      of inflammatory cells (haematoxylin-eosin, i.e. CD68-immunohistochemistry to
      detect macrophages), myelin damage (Kluver-Barrera staining) and intraneural
      haematoma. The grade of nerve injury was characterised by an objective score
      ranging from 0 (no injury) to 4 (severe injury). RESULTS: Fifty nerves were
      examined. According to the injury score applied, there was no significant
      difference between the pencil point needles [median (inter-quartile range) 2.0
      (2.0-2.0)] and the short bevelled-needle group [median 2.0 (2.0-2.0) P=0.23]. No
      myelin damage was observed. Signs of post-traumatic inflammation were equally
      distributed among both groups. CONCLUSIONS: In the present study, the magnitude
      of nerve injury after needle nerve perforation was not related to one of the
      applied needle types. Post-traumatic inflammation rather than structural damage
      of nerve tissue is the only notable sign of nerve injury after needle nerve
      perforation with either needle type. However, neither the pencil point- nor the
      short bevelled needle can be designated a less traumatic device.

PMID- 20701599
TI  - Outcomes may have been no better after trauma care in university-level intensive
      care units.

PMID- 20701601
TI  - Detection of prognostically relevant genetic abnormalities in childhood B-cell
      precursor acute lymphoblastic leukaemia: recommendations from the Biology and
      Diagnosis Committee of the International Berlin-Frankfurt-Munster study group.
AB  - Treatment of childhood acute lymphoblastic leukaemia (ALL) has improved
      considerably in recent years. A contributing factor has been the improved
      stratification for treatment according to a number of factors, including genetic
      determinants of outcome. Here we review the current diagnostic criteria of
      genetic abnormalities in precursor B-ALL (BCP-ALL), including the relevant
      technical approaches and the application of the most appropriate methods for the
      detection of each abnormality. The abnormalities with the most significant impact
      for treatment and management of BCP-ALL are t(9;22)(q34;q11)/BCR-ABL1,
      t(4;11)(q21;q23)/MLL-AFF1 and near-haploidy/low hypodiploidy for high risk
      stratification and, to a lesser extent, t(12;21)(p13;q22)/ETV6-RUNX1 and high
      hyperdiploidy for good risk management. Apart from the numerical abnormalities,
      these can be routinely tested for by reverse transcription polymerase chain
      reaction, providing a basic yet informative screen. However, cytogenetics,
      particularly fluorescence in situ hybridization may provide reliable alternative
      detection methods dependent upon the preferred technical approach within each
      protocol.

PMID- 20701600
TI  - Fat tissue, aging, and cellular senescence.
AB  - Fat tissue, frequently the largest organ in humans, is at the nexus of mechanisms
      involved in longevity and age-related metabolic dysfunction. Fat distribution and
      function change dramatically throughout life. Obesity is associated with
      accelerated onset of diseases common in old age, while fat ablation and certain
      mutations affecting fat increase life span. Fat cells turn over throughout the
      life span. Fat cell progenitors, preadipocytes, are abundant, closely related to
      macrophages, and dysdifferentiate in old age, switching into a pro-inflammatory,
      tissue-remodeling, senescent-like state. Other mesenchymal progenitors also can
      acquire a pro-inflammatory, adipocyte-like phenotype with aging. We propose a
      hypothetical model in which cellular stress and preadipocyte overutilization with
      aging induce cellular senescence, leading to impaired adipogenesis, failure to
      sequester lipotoxic fatty acids, inflammatory cytokine and chemokine generation,
      and innate and adaptive immune response activation. These pro-inflammatory
      processes may amplify each other and have systemic consequences. This model is
      consistent with recent concepts about cellular senescence as a stress-responsive,
      adaptive phenotype that develops through multiple stages, including major
      metabolic and secretory readjustments, which can spread from cell to cell and can
      occur at any point during life. Senescence could be an alternative cell fate that
      develops in response to injury or metabolic dysfunction and might occur in
      nondividing as well as dividing cells. Consistent with this, a senescent-like
      state can develop in preadipocytes and fat cells from young obese individuals.
      Senescent, pro-inflammatory cells in fat could have profound clinical
      consequences because of the large size of the fat organ and its central metabolic
      role.

PMID- 20701604
TI  - Lobular neoplasia of the breast.
AB  - Lobular neoplasia is increasingly being detected, probably due to the widespread
      screening for breast malignancies. The understanding of lobular neoplasia is
      undergoing a paradigm shift, from being considered a predictor of recurrence to
      being considered a pre-invasive lesion, based on molecular studies suggesting a
      clonal link with invasive lobular cancer. The management of patients diagnosed to
      have lobular neoplasia is in evolution, with the increasing need for risk
      stratification and hence the necessity to identify this entity separately as
      either lobular carcinoma in-situ and atypical lobular hyperplasia. The
      indications for wide local excision for patients diagnosed to have lobular
      neoplasia on biopsy are being defined. The evidence for preventive strategies
      like hormonal treatment with Tamoxifen or aromatase inhibitors for high risk
      patients is increasing, with the results from prospective interventional trials.
      The role of screening magnetic resonance imaging for surveillance of high risk
      patients with lobular neoplasia is under evaluation.

PMID- 20701603
TI  - Plasma cell leukaemia and other aggressive plasma cell malignancies.
AB  - Extramedullary plasma cell cancers, such as plasma cell leukaemia (PCL) and
      multiple extramedullary plasmacytomas (MEP) are very aggressive malignancies.
      These can be primary (de-novo) or secondary due to progressive prior multiple
      myeloma (MM). Recent reports suggest an increase in incidence of these disorders.
      Compared to MM, organ invasion is common in PCL, while soft tissue tumors
      involving the head, neck or paraspinal area are common sites for MEP. Markers of
      poor prognosis are frequently observed in these extramedullary forms of plasma
      cell cancers, and survival is significantly inferior compared to patients with
      MM. Conventional chemotherapeutic and radiotherapy approaches have been employed
      with variable results. Even high dose chemotherapy with autologous stem cell
      rescue has not been able to demonstrate consistent improvement in survival
      outcome. Although not specifically evaluated, novel anti-plasma cell agents, such
      as the proteasome inhibitor bortezomib, and immunomodulatory drugs, such as
      lenalidomide, appear to be active against these aggressive cancers. Clinical and
      translational research directed at improved understanding of disease biology and
      development of novel therapeutics is urgently needed.

PMID- 20701602
TI  - The NF (Nuclear factor)-kappaB inhibitor parthenolide interacts with histone
      deacetylase inhibitors to induce MKK7/JNK1-dependent apoptosis in human acute
      myeloid leukaemia cells.
AB  - Interactions between the nuclear factor (NF)-kappaB inhibitor parthenolide and
      the pan-histone deacetylase inhibitors (HDACIs) vorinostat and LBH589 were
      investigated in human acute myeloid leukaemia (AML) cells, including primary AML
      blasts. Co-administration of parthenolide blocked HDACI-mediated
      phosphorylation/activation of IKK and RelA/p65 in association with increased JNK1
      activation in various AML cell types. These events were accompanied by an
      increase in apoptosis in multiple AML cell lines (e.g. U937, HL-60, NB4, MV-4-11,
      and MOLM-13). Significantly, parthenolide also increased HDACI-mediated cell
      death in haematopoietic cells transduced with the MLL-MLLT1 fusion gene, which
      exhibit certain leukaemia-initiating cell characteristics, as well as primary AML
      blasts. Exposure to parthenolide/HDACI regimens clearly inhibited the growth of
      AML-colony-forming units but was relatively sparing toward normal haematopoietic
      progenitors. Notably, blockade of c-Jun N-terminal kinase (JNK) signalling by
      either pharmacological inhibitors or genetic means (e.g. dominant-negative JNK1
      or JNK1 shRNA) diminished parthenolide/HDACI-mediated lethality. Moreover,
      dominant-negative MKK7, but not dominant-negative MKK4/SEK1, blocked JNK1
      activation and apoptosis induced by parthenolide/HDACI regimens. Together, these
      findings indicate that parthenolide potentiates HDACI lethality in human AML
      cells through a process involving NF-kappaB inhibition and subsequent MKK7
      dependent activation of the SAPK/JNK pathway. They also raise the possibility
      that this strategy may target leukaemic progenitor cells.

PMID- 20701605
TI  - HIF-1alpha and locally advanced breast cancer.

PMID- 20701606
TI  - Inflammatory pseudotumor of the breast: a mimic of breast carcinoma.

PMID- 20701607
TI  - Combined effects of lapatinib and bortezomib in human epidermal receptor 2 (HER2)
      overexpressing breast cancer cells and activity of bortezomib against lapatinib
      resistant breast cancer cells.
AB  - Lapatinib and bortezomib are highly active against breast cancer cells. Breast
      cancer patients who initially respond to lapatinib may eventually manifest
      acquired resistance to this treatment. Thus, the identification of novel agents
      that may prevent or delay the development of acquired resistance to lapatinib is
      critical. In the current study, we show that the combination of lapatinib and
      bortezomib results in a synergistic growth inhibition in human epidermal receptor
      2 (HER2)-overexpressing breast cancer cells and that the combination enhances
      apoptosis of SK-BR-3 cells. Importantly, we found that the combination of
      lapatinib plus bortezomib more effectively blocked activation of the HER2 pathway
      in SK-BR-3 cells, compared with monotherapy. In addition, we established a model
      of acquired resistance to lapatinib by chronically challenging SK-BR-3 breast
      cancer cells with increasing concentrations of lapatinib. Here, we showed that
      bortezomib notably induced apoptosis of lapatinib-resistant SK-BR-3 pools and
      further inhibited HER2 signaling in the resistant cells. Taken together, the
      current data indicate a synergistic interaction between lapatinib and bortezomib
      in HER2-overexpressing breast cancer cells and provide the rationale for the
      clinical evaluation of these two noncross-resistant targeted therapies. The
      combination of lapatinib and bortezomib may be a potentially novel approach to
      prevent or delay the onset of acquired resistance to lapatinib in HER2
      overxpressing/estrogen receptor (ER)-negative breast cancers.

PMID- 20701608
TI  - A defucosylated anti-CD317 antibody exhibited enhanced antibody-dependent
      cellular cytotoxicity against primary myeloma cells in the presence of effectors
      from patients.
AB  - The humanized monoclonal antibody (mAb) against CD317 antigen (anti-HM1.24
      antibody; AHM), which is highly expressed on multiple myeloma (MM), induces
      antibody-dependent cellular cytotoxicity (ADCC). However, the antitumor activity
      of AHM in the clinical setting has not been clearly demonstrated. In this study,
      we produced defucosylated AHM and evaluated its potency for clinical application
      by performing autologous ADCC assays against primary MM cells from patients.
      Defucosylated AHM that was produced in rat myeloma YB2/0 cells expressing a low
      level of fucosyltransferase (FUT8) showed significant ADCC activity against three
      out of six primary MM cells in the presence of autologous PBMC, whereas
      conventional AHM did not. The results indicate that the potency of AHM to induce
      ADCC against primary MM cells was insufficient, but was significantly augmented
      by defucosylation. To generate more homogenous defucosylated monoclonal
      antibodies (mAb) for fermentation, we disrupted the GFT gene that encodes a GDP
      fucose transporter in a CHO/DXB11 cell line by sequential homologous
      recombination. Analysis of the N-linked oligosaccharide in the defucosylated AHM
      produced by the established GFT(-/-)CHO cell line showed that a majority (93.4%)
      of the oligosaccharide was fucose free. The GFT(-/-) cells stably produced
      defucosylated mAb over passages. These results demonstrate that GTF(-/-)CHO
      produced defucosylated AHM (GFTKO-AHM) will be a promising new therapeutic
      antibody against MM in the clinical setting.

PMID- 20701609
TI  - MicroRNA-21 expression in neonatal blood associated with antenatal immunoglobulin
      E production and development of allergic rhinitis.
AB  - BACKGROUND: The prevalence of allergic diseases has increased in the past
      decades. It is unknown whether expression of certain microRNAs (miRNAs) in
      neonatal leucocytes is correlated to IgE production and/or allergic diseases.
      OBJECTIVE: This study investigated the association of miRNA expression in
      neonatal leucocytes with cord blood IgE (CBIgE) elevation and development of
      allergic disease. METHODS: We screened for the expression of a panel of 157
      miRNAs in mononuclear leucocytes from human umbilical cord blood (CB) samples
      with elevated CBIgE and tracked the association of down-regulated miRNA
      expression to the miRNA-targeted gene expression and to children with allergic
      rhinitis (AR). RESULTS: Among the initial screen of 10 CB samples with elevated
      CBIgE, expression of eight of the 157 miRNAs was low. Of these eight down
      expressed miRNAs, three remained down-regulation in a validation with other 20 CB
      samples, and two of the three miRNAs, miR-21 and miR-126, were significantly
      lower in monocytes from AR children. Further analysis of mRNA expression of the
      miR-21-targeted genes identified that TGFBR2 expression on monocytes was
      significantly up-regulated in CB with elevated CBIgE, and in AR patients.
      Transfection of miR-21 precursor into monocytes from patients with AR increased
      miR-21 expression and decreased TGFBR2 expression. CONCLUSION: This study
      demonstrated the first in the literature that lower miR-21 expression in CB and
      increased TGFBR2 expression is associated with antenatal IgE production and
      development of AR.

PMID- 20701610
TI  - Lupin allergy: a hidden killer in the home.
AB  - This review addresses the problem of lupin sensitization in the home environment.
      We summarize the data currently available on allergy to lupin, which has become,
      in recent years, a hidden killer in our homes. Since 2006, when lupin was
      included in European regulations as a food whose presence must be declared, the
      situation may have changed. Nevertheless, we must take into account the
      possibility of undeclared allergenic ingredients or the presence of 'hidden'
      allergens, given that contamination during food production processes may be a
      great risk for sensitized individuals. Furthermore, the United States, Japan,
      Australia and New Zealand still do not include lupin among the ingredients that
      must be listed on foodstuff labelling. Our responsibility is to educate the
      public so that they are aware of the danger and look for lupin in the labels of
      products that run the risk of containing it. Lupin allergy can manifest itself in
      isolation or in parallel to peanut allergy. Identification of the proteins
      causing possible cross-reactivity is complicated, and new structural studies are
      needed. To date, it has not been possible to clearly identify the allergens
      responsible for isolated lupin sensitization in relation to parallel and/or cross
      sensitization between lupin and peanut. Most of the allergenic proteins of lupin
      are alpha- and beta-conglutins, with a lesser presence of gamma- and delta
      conglutins. A beta-conglutin corresponding to Lup an 1, with a sequence similar
      to Ara h 1, has been identified as a major allergen of lupin in patients with
      allergy following lupin ingestion.

PMID- 20701611
TI  - Role of gender disparity of circulating high-sensitivity C-reactive protein
      concentrations and obesity on asthma in Taiwan.
AB  - BACKGROUND: Several studies have suggested that the association between obesity
      and asthma may be stronger in females than in males, but the reason is still
      unclear. OBJECTIVE: The aim of this study was to investigate whether differences
      in high-sensitivity C-reactive protein (hs-CRP) levels explain why obesity is
      associated with asthma in females but not in males. METHODS: This study
      prospectively enrolled 754 subjects >= 18 years old from hospital-based asthma
      patients and population-based controls. We measured adiposity factors [body mass
      index (BMI), waist circumference and waist-hip ratio], hs-CRP and total IgE
      levels. RESULTS: After adjusting for potential confounding factors, we found a
      significant association between BMI and asthma in females with a significant
      interaction of gender and BMI on asthma (chi(2) =10.2, P=0.004). If hs-CRP was
      added to the logistic model, the interaction was attenuated but still significant
      (chi(2) =7.02, P=0.03). After adjusting for BMI, we did not find that circulating
      hs-CRP concentrations were significantly associated with asthma in males and
      females. CONCLUSION: We found that BMI was associated with asthma in females, but
      our results do not support the suggestion that hs-CRP levels contribute
      significantly to the link between obesity and asthma with respect to gender
      disparity.

PMID- 20701613
TI  - Basophil activation test is better but not good enough for the diagnosis of
      hymenoptera venom allergy: the problem of cross-reactive carbohydrate
      determinants.

PMID- 20701614
TI  - Interleukin-17: a new role in steroid hypo-responsiveness?

PMID- 20701615
TI  - T cell inflammatory response, Foxp3 and TNFRS18-L regulation of peripheral blood
      mononuclear cells from patients with nasal polyps-asthma after staphylococcal
      superantigen stimulation.
AB  - BACKGROUND: Staphylococcal superantigens may modulate airway inflammatory
      disease. OBJECTIVE: We assessed the effect of Staphylococcus aureus enterotoxin B
      (SEB) on T cell activation in patients with nasal polyps and asthma, and its
      possible link to aspirin hypersensitivity. METHODS: Leucocytes were isolated from
      five healthy subjects (controls), five asthmatics with nasal polyps without (NP
      ATA) and five with aspirin-induced asthma (NP-AIA). Cells were incubated with
      increasing concentrations of SEB for 4 and 18 h. Release of T(H)1/T(H)2 cytokines
      was assessed by Cytometric Bead-Array. Foxp3 and TNFRS18-L expression were
      analysed by qPCR and flow cytometry. RESULTS: After 4 and 18 h, SEB significantly
      increased IFN-gamma, IL-4, TNF-alpha, IL-5 and IL-2 concentrations in
      supernatants of both NP polyp groups compared with controls. Baseline Foxp3 was
      significantly decreased in both NP-asthma groups. Incubation with SEB for 4 h
      induced a limited up-regulation of Foxp3 in NP-AIA patients, which was switched
      off consecutively. Foxp3 was significantly up-regulated in the control group
      after 18 h, but not in the NP-asthmatic groups. In parallel, TNFRS18-L mRNA
      significantly increased after 18 h in the NP-asthma groups compared with control
      subjects. This molecule was highly expressed in CD11c(+)CD14(+) cells and its
      levels increased after 18 and 24 h culture in the NP-asthma patients. CONCLUSION:
      SEB induces both T(H)1 and T(H)2 pro-inflammatory responses in patients with
      nasal polyps and asthma regardless of the presence of aspirin hypersensitivity.
      The nature of this response may be linked to a basal deficiency of Foxp3 observed
      in the NP-asthmatic patients and/or to the up-regulation of TNFRS18-L on
      monocytes/dendritic cell precursors.

PMID- 20701616
TI  - Characterization of peach thaumatin-like proteins and their identification as
      major peach allergens.
AB  - BACKGROUND: Peach is the most important fruit related to food allergy in the
      Mediterranean area. Pru p 3, its lipid transfer protein, has been described as
      the principal allergen responsible for cross-reactivities with other foods and
      pollen and the severity of clinical symptoms. However, the involvement of other
      allergenic families cannot be ruled out. Thaumatin-like proteins (TLPs) have been
      described as food allergen in several fruits, such as apple, cherry, kiwi and
      banana, and pollen. OBJECTIVE: To identify members of the TLP family in peach
      fruit and to characterize putative allergens. METHODS: Through two-dimensional
      (2D) electrophoresis of peach extract and immunodetections with a pool of peach
      allergic patients, IgE-binding spots were identified and the corresponding
      proteins purified and characterized as allergens by in vitro and in vivo assays.
      Three isoforms, belonging to the TLP family, were purified by different
      chromatographic systems and characterized by N-terminal amino acid sequences,
      molecular weight determination (MALDI) and enzymatic activity analysis (beta-1,3
      gluconase test and inhibition growth of fungi). In the same way, their IgE
      binding capacity and allergenic activity were tested by ELISA assays, basophil
      activation tests and skin prick tests (SPT). RESULTS: Two peach-TLPs, Pru p
      2.0101 and Pru p 2.0201, were identified as IgE-binding spots by 2D
      electrophoresis. Another peach-TLP, Pru p 2.0301, was cloned and produced as
      recombinant protein in a yeast system. The three isoforms were purified and
      characterized as TLPs by immunoblotting with anti-chestnut TLP antibodies and
      anti-plant N-asparagine complex glycan (anti-cross-reactive carbohydrate
      determinant). All of them showed beta-1,3-glucanase activity and inhibition of
      fungal growth. The three TLPs were recognized by around 50% of the sera from 31
      patients analysed in ELISA experiments. All three gave a positive response to an
      SPT and/or in basophil activation experiments. CONCLUSION: Three isoforms,
      belonging to the TLP family, were identified in peach as principal allergens.
      Their prevalence, observed in in vitro, ex vivo and in vivo analyses, suggests
      that they are important allergens and should therefore be included in the routine
      diagnosis of peach allergy, at least in the Mediterranean area.

PMID- 20701617
TI  - Sublingual immunotherapy affects transforming growth factor-beta and nasal
      eosinophils.

PMID- 20701619
TI  - Bacteraemia following dental implants' placement.
AB  - OBJECTIVE: To investigate the prevalence, duration and aetiology of bacteraemias
      following the placement of implants as well as the prophylactic efficacy of a
      chlorhexidine digluconate (CHX) mouthrinse. MATERIAL AND METHODS: Fifty patients
      undergoing implant placement were randomly distributed into two groups: CONTROL
      GROUP: 30 patients with no prophylactic intervention before surgery. CHX group:
      20 patients who performed a 0.2% CHX mouthrinse before surgery. Blood samples
      were collected at baseline, at 30 s after the insertion of implants and at 15 min
      after completion of the suturing of the mucoperiosteal flap. Samples were
      processed in the Bactec 9240, and the subculture and further identification of
      the isolates were performed using conventional microbiological techniques.
      RESULTS: The prevalence of bacteraemias was 2% at baseline. In the control group,
      the prevalence of bacteraemias was 6.7% at 30 s and 3.3% at 15 min, but no
      statistically significant differences were achieved compared with the baseline
      percentage. In the CHX group, there were no positive cultures from blood samples
      obtained at 30 s or at 15 min. CONCLUSIONS: Implant placement via a
      mucoperiosteal flap does not carry a significant risk of developing bacteraemias.
      The use of antibiotic prophylaxis for the prevention of focal infections such as
      bacterial endocarditis in "at-risk" patients undergoing dental implants is
      therefore questionable. Although its efficacy has not been confirmed
      statistically, we recommend a 0.2% CHX mouthrinse before treatment as proposed
      previously by the British Society for Antimicrobial Chemotherapy.

PMID- 20701620
TI  - Early loading of single crowns supported by 6-mm-long implants with a moderately
      rough surface: a prospective 2-year follow-up cohort study.
AB  - AIM: To evaluate prospectively the clinical and radiographic outcomes after 2
      years of loading of 6 mm long moderately rough implants supporting single crowns
      in the posterior regions. MATERIAL AND METHODS: Forty SLActive Straumann short (6
      mm) implants were placed in 35 consecutively treated patients. Nineteen implants,
      4.1 mm in diameter, and 21 implants, 4.8 mm in diameter, were installed. Implants
      were loaded after 6 weeks of healing. Implant survival rate, marginal bone loss
      and resonance frequency analysis (RFA) were evaluated at different intervals. The
      clinical crown/implant ratio was also calculated. RESULTS: Two out of 40 implants
      were lost before loading. Hence, the survival rate before loading was 95%. No
      further technical or biological complications were encountered during the 2-year
      follow-up. The mean marginal bone loss before loading was 0.34+/-0.38 mm. After
      loading, the mean marginal bone loss was 0.23+/-0.33 and 0.21+/-0.39 mm at the 1-
      and 2-year follow-ups. The RFA values increased between insertion (70.2+/-9) and
      the 6-week evaluation (74.8+/-6.1). The clinical crown/implant ratio increased
      with time from 1.5 at the delivery of the prosthesis to 1.8 after 2 years of
      loading. CONCLUSION: Short implants (6 mm) with a moderately rough surface loaded
      early (after 6 weeks) during healing yielded high implant survival rates and
      moderate loss of bone after 2 years of loading. Longer observation periods are
      needed to draw more definite conclusions on the reliability of short implants
      supporting single crowns.

PMID- 20701621
TI  - Benefits of dental implants installed during ablative tumour surgery in oral
      cancer patients: a prospective 5-year clinical trial.
AB  - OBJECTIVE: This prospective study assessed treatment outcome and patient
      satisfaction of oral cancer patients with a mandibular overdenture on implants up
      to 5 years after treatment. MATERIALS AND METHODS: At baseline, 50 consecutive
      edentulous oral cancer patients, in whom prosthetic problems were expected after
      oncological treatment, were evaluated by standardized questionnaires and clinical
      assessments. All implants were installed during ablative tumour surgery in native
      bone in the interforaminal area. About two-thirds of the patients (n=31) had
      radiotherapy post-surgery (dose >40 Gy in the interforaminal area). RESULTS: At
      the 5-year evaluation, 26 patients had passed away and four patients had to be
      excluded from the analyses, because superstructures were not present, due to
      persistent local irritation (n=2), loss of three implants (n=1) and the
      impossibility of making an overdenture related to tumour and oncological surgery
      driven anatomical limitations (n=1). In the remaining 20 patients, the prosthesis
      was still in function (76 implants). During the 5-year follow-up, total 14
      implants were lost, 13 in irradiated bone (survival rate 89.4%, dose >40 Gy) and
      one in non-irradiated bone (survival rate 98.6%). Peri-implant tissues had a
      healthy appearance and remained healthy over time. Patients were satisfied with
      their dentures. CONCLUSIONS: It was concluded that oral cancer patients can
      benefit from implants installed during ablative surgery, with a high survival
      rate of the implants, a high percentage of rehabilitated patients and a high
      denture satisfaction up to 5 years after treatment.

PMID- 20701622
TI  - Abstracts of the Fifth Annual Meeting of the European Society of Coloproctology.
      September 22-25, 2010. Sorrento, Italy.

PMID- 20701623
TI  - The plant pathogen Pseudomonas fuscovaginae contains two conserved quorum sensing
      systems involved in virulence and negatively regulated by RsaL and the novel
      regulator RsaM.
AB  - Pseudomonas fuscovaginae is a Gram-negative fluorescent pseudomonad pathogenic
      towards several plant species. Despite its importance as a plant pathogen, no
      molecular studies of virulence have thus far been reported. In this study we show
      that P. fuscovaginae possesses two conserved N-acyl homoserine lactone (AHL)
      quorum sensing (QS) systems which we designated PfsI/R and PfvI/R. The PfsI/R
      system is homologous to the BviI/R system of Burkholderia vietnamiensis and
      produces and responds to C10-HSL and C12-HSL whereas PfvI/R is homologous to the
      LasI/R system of Pseudomonas aeruginosa and produces several long-chain 3-oxo
      HSLs and responds to 3-oxo-C10-HSL and 3-oxo-C12-HSL and at high AHL
      concentrations can also respond to structurally different long-chain AHLs. Both
      systems were found to be negatively regulated by a repressor protein which was
      encoded by a gene located intergenically between the AHL synthase and LuxR-family
      response regulator. The pfsI/R system was regulated by a novel repressor
      designated RsaM while the pfvI/R system was regulated by both the RsaL repressor
      and by RsaM. The two systems are not transcriptionally hierarchically organized
      but share a common AHL response and both are required for plant virulence.
      Pseudomonas fuscovaginae has therefore a unique complex regulatory network
      composed of at least two different repressors which directly regulate the AHL QS
      systems and pathogenicity.

PMID- 20701624
TI  - Evaluation of PG-M3 antibody in the diagnosis of acute promyelocytic leukaemia.
AB  - BACKGROUND & OBJECTIVES: Acute promyelocytic leukaemia (APL) is a distinct
      subtype of acute myeloid leukaemia (AML) characterized by a reciprocal
      translocation, t(15;17) and a high incidence of life-threatening coagulopathy.
      APL diagnosis is considered a medical emergency. As reverse transcription
      polymerase chain reaction (RT-PCR) for PML-RAR fusion oncoprotein is time
      consuming, there is a need for a rapid and accurate diagnostic test for APL. This
      study evaluates the role of PG-M3 monoclonal antibody using immunofluorescence
      (IF) in the early diagnosis of APL. MATERIALS AND METHODS: Thirty-six new
      untreated APL cases diagnosed with RT-PCR for PML-RAR as the gold standard and 38
      non-APL controls (28 non-APL AMLs and 10 non-leukaemic samples) were evaluated by
      routine morphology and cytochemistry, RT-PCR and IF using PG-M3 monoclonal
      antibody. RESULTS: Using IF, 34 of 36 (94.4%) APL cases showed a microgranular
      pattern suggestive of APL and two cases (5.6%) showed a speckled pattern typical
      of wild-type PML protein (False negative). By comparison, two of 28 (7.1%) non
      APL AMLs showed microgranular pattern (false positive). Hence, IF as a diagnostic
      test for APL resulted in a sensitivity of 94.4%, specificity of 92.9% and
      positive and negative predictive values of 94.4% and 92.9% respectively. All 10
      non-leukaemic samples showed a speckled pattern. CONCLUSIONS: IF using PG-M3
      antibodies can be used as a rapid (takes 2 h), cheap, sensitive and specific
      method to identify APL. It can be a useful adjunct for diagnosis of APL
      especially if facilities for RT-PCR are not available, particularly in resource
      limited settings.

PMID- 20701625
TI  - Lipid assessment, metabolic syndrome and coronary heart disease risk.
AB  - BACKGROUND: Although the total to high-density lipoprotein cholesterol ratio
      (TC/HDL-C) has been used for decades to identify individuals at risk for coronary
      heart disease (CHD), apolipoprotein-based (apolipoprotein B/apolipoprotein A-I
      [apoB/apoA-I]) and nuclear magnetic resonance spectroscopy (NMR)-based
      lipoprotein concentrations (low-density lipoprotein(NMR) /high-density
      lipoprotein(NMR) [LDL(NMR) /HDL(NMR)]) may also be useful for CHD risk
      stratification. MATERIALS AND METHODS: In a case-control study conducted within
      the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk
      study population, 870 individuals who developed CHD during a 6-year follow-up
      were matched to 1659 controls on the basis of gender, age and enrollment time.
      LDL(NMR) and HDL(NMR) were measured by proton NMR spectroscopy. RESULTS: After
      adjusting for traditional CHD risk factors, men in the top quintile of the
      various lipoprotein ratios proved to be at increased CHD risk (OR = 2.59 [95% IC,
      1.76-3.83] for TC/HDL-C ratio, 2.59 [1.75-3.83] for apoB/apoA-I ratio and 2.78
      [1.86-4.17] for LDL(NMR) /HDL(NMR) ratio) compared with men in the bottom
      quintile. Similar associations were observed in women (OR = 2.86 [1.71-4.80] for
      TC/HDL-C ratio, 2.94 [1.74-4.97] for apoB/apoA-I ratio and 2.03 [1.21-3.43] for
      LDL(NMR)/HDL(NMR) ratio). Compared with participants with only one component of
      the metabolic syndrome, those who had five had an increased TC/HDL-C ratio (73.0%
      and 80.4% in men and women respectively), apoB/apoA-I ratio (58.0% and 62.9% in
      men and women respectively) and for LDL(NMR)/HDL(NMR) ratio (52.6% and 54.1% in
      men and women respectively). CONCLUSION: In this European study population, the
      TC/HDL-C, apoB/apoA-I and LDL(NMR) /HDL(NMR) ratios were similarly associated
      with components of the metabolic syndrome and CHD risk.

PMID- 20701627
TI  - Anti-annexin 1 antibodies: a new diagnostic marker in the serum of patients with
      discoid lupus erythematosus.
AB  - Annexin 1 is an anti-inflammatory molecule and has also been described to be a
      common target of autoantibodies. In this study, we determined whether antibodies
      against annexin 1 can be detected in sera of patients with cutaneous lupus
      erythematosus (CLE). Levels of anti-annexin 1 antibodies were evaluated by a new
      established enzyme-linked immunosorbent assay and found to be significantly
      higher in sera of patients with CLE when compared to normal healthy donors (NHD).
      Moreover, the percentage of sera positively tested for anti-annexin 1 antibodies
      was elevated in patients with CLE when compared to NHD. In particular, the
      percentage of positive sera for anti-annexin 1 antibodies was significantly
      higher in patients with discoid lupus erythematosus (DLE); however, disease
      activity did not correlate with the antibody levels. The results of this study
      indicate that anti-annexin 1 antibodies in sera of patients with DLE might be a
      valuable aid in the diagnosis of this subtype.

PMID- 20701626
TI  - Iron sensitizes keratinocytes and fibroblasts to UVA-mediated matrix
      metalloproteinase-1 through TNF-alpha and ERK activation.
AB  - Oestrogen deficiency is regarded as the main causative factor in postmenopausal
      skin ageing and photoageing. While women after menopause experience low levels of
      oestrogen because of cease of ovarian function, they are also exposed to high
      levels of iron as a result of cessation of menstruation. In this study, we
      investigated whether this increase in iron presents a risk to the postmenopausal
      skin. Because of the lack of appropriate animal models to closely mimic the low
      oestrogen and high iron conditions, we tested the hypothesis in a high iron and
      low oestrogen culture model. Here, we showed that primary human dermal
      fibroblasts exposed to iron did not affect the baseline levels of matrix
      metalloproteinase-1 (MMP-1) activity. However, the iron-exposed fibroblasts were
      sensitized to UVA exposure, which resulted in a synergistic increase in MMP-1.
      UVA activated the three members of MAPK family: ERKs, p38, and JNKs. Additional
      activation of ERKs by iron contributed to the synergistic increases. Primary
      normal human epidermal keratinocytes (NHEK) did not respond to iron or UVA
      exposure as measured by MMP-1, but produced tumor necrosis factor-alpha (TNF
      alpha) in the media, which then stimulated MMP-1 in fibroblasts. Our results
      indicate that iron and UVA increase MMP-1 activity in dermal fibroblasts not only
      directly through ERK activation but also by an indirect paracrine loop through
      TNF-alpha released by NHEK. We conclude that in addition to oestrogen deficiency,
      increased iron as a result of menopause could be a novel risk factor by
      sensitizing postmenopausal skin to solar irradiation.

PMID- 20701628
TI  - L-ascorbic acid 2-phosphate represses the dihydrotestosterone-induced dickkopf-1
      expression in human balding dermal papilla cells.
AB  - Recent studies suggested that dihydrotestosterone (DHT)-driven alteration in the
      autocrine and paracrine factors may be a key to androgen-potentiated balding.
      Also, we recently claimed that DHT-inducible dickkopf-1 (DKK-1) is one of the key
      factors involved in the androgen-potentiated balding. Here, we investigated
      whether L-ascorbic acid 2-phosphate (Asc 2-P), a derivative of L-ascorbic acid,
      could attenuate DHT-induced DKK-1 expression in dermal papilla cells (DPCs) from
      balding scalp. We observed that DHT-induced DKK-1 mRNA expression was attenuated
      in the presence of Asc 2-P as examined by RT-PCR analysis. In addition, we found
      that DHT-induced activation of luciferase reporter activity was significantly
      repressed when Asc 2-P was added together with DHT. Moreover, Asc 2-P repressed
      DHT-induced DKK-1 protein expression as examined by enzyme-linked immunosorbent
      assay (ELISA). Although there will be many hurdles to apply our finding to actual
      remedies, these results suggest that it would be worthy to evaluate Asc 2-P or
      its derivatives for the treatment and prevention of androgen-driven balding.

PMID- 20701629
TI  - Mechanistic study of endogenous skin lesions in diabetic rats.
AB  - Pathological and physiological changes in dermal tissue in a rat model of
      diabetes mellitus (DM) were investigated. Sixteen male 8-week-old Sprague-Dawley
      rats were randomized into two groups of eight, the DM group (Group DM) and the
      normal control group (Group (NC) normal control). Group DM rats were injected
      with streptozotocin (STZ) intraperitoneally at a dose of 65 mg/kg body weight.
      Group NC rats were injected with the same volume of citric acid buffer. All rats
      were sacrificed 12 weeks later. The impact of exposure to (AGE) advanced
      glycation end products-modified human serum albumin (AGE-HSA) on epidermal cells
      and ECV304 cells was evaluated in cell culture experiments. The diabetic rats
      exhibited changes in skin tissue, including a decrease in thickness,
      disappearance of the multilayer epithelium structure, degeneration of collagen
      fibres and an increase in the infiltration of inflammatory cells, in addition to
      a significant increase in skin glucose and AGEs. Moreover, diabetic rats had
      increased plasma glycosylated protein (GSP) and malondialdehyde (MDA) and
      decreased plasma glutathione (GSH). The percentage of epidermal cells in S phase
      was similar between the two group rats; however, there was a marked decrease in
      the G2/M phase in Group DM. Additionally, exposure of ECV304 cells to AGE-HSA led
      to a time-dependent and dose-dependent increase in apoptosis. Therefore, the high
      glucose in the skin tissue, coupled with the accumulation of toxic substances
      such as AGEs, promote the dysfunction of dermal cells and/or the matrix. This may
      be a significant mechanism of diabetes-induced early-stage endogenous skin
      damage.

PMID- 20701630
TI  - In vitro and in vivo analysis of pro- and anti-inflammatory effects of weak and
      strong contact allergens.
AB  - Inflammation is a crucial step in the development of allergic contact dermatitis.
      The primary contact with chemical allergens, called sensitization, and the
      secondary contact, called elicitation, result in an inflammatory response in the
      skin. The ability of contact allergens to induce allergic contact dermatitis
      correlates to a great extent with their inflammatory potential. Therefore, the
      analysis of the sensitizing potential of a putative contact allergen should
      include the examination of its ability and potency to cause an inflammation. In
      this study, we examined the inflammatory potential of different weak contact
      allergens and of the strong sensitizer 2,4,6-trinitrochlorobenzene (TNCB) in
      vitro and in vivo using the contact hypersensitivity model, the mouse model for
      allergic contact dermatitis. Cytokine induction was analysed by PCR and ELISA to
      determine mRNA and protein levels, respectively. Inflammation-dependent
      recruitment of skin-homing effector T cells was measured in correlation with the
      other methods. We show that the sensitizing potential of a contact allergen
      correlates with the strength of the inflammatory response. The different methods
      used gave similar results. Quantitative cytokine profiling may be used to
      determine the sensitizing potential of chemicals for hazard identification and
      risk assessment.

PMID- 20701633
TI  - The North Atlantic subpolar gyre and the marine migration of Atlantic salmon
      Salmo salar: the 'Merry-Go-Round' hypothesis.
AB  - One model for marine migration of Atlantic salmon Salmo salar proposes that North
      American and southern European stocks (<62 degrees N) move directly to feeding
      grounds off west Greenland, then overwinter in the Labrador Sea, whereas northern
      European stocks (>62 degrees N) utilize the Norwegian Sea. An alternate model
      proposes that both North American and European stocks migrate in the North
      Atlantic Subpolar Gyre (NASpG) where S. salar enter the NASpG on their respective
      sides of the Atlantic, and travel counterclockwise within the NASpG until
      returning to natal rivers. A review of data accumulated during the last 50 years
      suggests a gyre model is most probable. Freshwater parr metamorphose into smolts
      which have morphological, physiological and behavioural adaptations of
      epipelagic, marine fishes. Former high-seas fisheries were seasonally sequential
      and moved in the direction of NASpG currents, and catches were highest along the
      main axis of the NASpG. Marking and discrimination studies indicate mixed
      continental origin feeding aggregations on both sides of the Atlantic. Marked
      North American smolts were captured off Norway, the Faroe Islands, east and west
      Greenland, and adults tagged at the Faroes were recovered in Canadian rivers.
      Marked European smolts were recovered off Newfoundland and Labrador, west and
      east Greenland, and adults tagged in the Labrador Sea were captured in European
      rivers. High Caesium-137 ((137)Cs) levels in S. salar returning to a Quebec river
      suggested 62.3% had fed at or east of Iceland, whereas levels in 1 sea-winter
      (SW) Atlantic Canada returnees indicated 24.7% had fed east of the Faroes. Lower
      levels of (137)Cs in returning 1SW Irish fish suggest much of their growth
      occurred in the western Atlantic. These data suggest marine migration of S. salar
      follows a gyre model and is similar to other open-ocean migrations of epipelagic
      fishes.

PMID- 20701634
TI  - Knodus dorsomaculatus (Characiformes: Characidae), a new species from Teles Pires
      River, Tapajos River basin, Brazil.
AB  - Knodus dorsomaculatus, a new species, is described from Teles Pires River, a
      tributary of the Tapajos River, Brazil. It can be distinguished from its
      congeners by the presence of a conspicuous dark blotch on the base of the first
      five branched dorsal fin rays and the presence of ii,9 dorsal fin rays.
      Additional comparisons between K. dorsomaculatus and its congeners are presented.

PMID- 20701635
TI  - Multiple paternity and variance in male fertilization success within Atlantic
      salmon Salmo salar redds in a naturally spawning population.
AB  - The incidence and magnitude of multiple paternity were estimated for a natural,
      unmanipulated spawning population of Atlantic salmon Salmo salar. Egg nests were
      surveyed in the autumn and sub-samples were excavated the following spring.
      Parentage data derived from microsatellite DNA revealed an unexpectedly high
      level of multiple paternity. Within a single redd, females may mate with as many
      as 16 different males, including small mature male parr and large anadromous
      males. Multiple paternity was most pronounced in areas of highest redd density,
      corresponding with increased abundances of mature male parr. In addition, there
      was considerable variation in success among males, although this variability did
      not depend upon the number of males participating in spawning. This work
      underscores the value of undertaking genetic studies on the mating systems of
      fishes in unmanipulated, natural environments.

PMID- 20701636
TI  - The reproductive cycle of female Ballan wrasse Labrus bergylta in high latitude,
      temperate waters.
AB  - This 2 year study examined the reproductive cycle of wild female Ballan wrasse
      Labrus bergylta in western Norway as a precursor to captive breeding trials.
      Light microscopy of ovarian histology was used to stage gonad maturity and enzyme
      linked immuno-absorbent assay (ELISA) to measure plasma concentrations of the sex
      steroids testosterone (T) and 17beta-oestradiol (E(2)). Ovarian recrudescence
      began in late autumn to early winter with the growth of previtellogenic oocytes
      and the formation of cortical alveoli. Vitellogenic oocytes developed from
      January to June and ovaries containing postovulatory follicles (POF) were present
      between May and June. These POF occurred simultaneously among other late maturity
      stage oocytes. Plasma steroid concentration and organo-somatic indices increased
      over winter and spring. Maximal (mean +/-s.e.) values of plasma T (0.95 +/- 0.26
      ng ml(-1)), E(2) (1.75 +/- 0.43 ng ml(-1)) and gonado-somatic index (I(G); 10.71
      +/- 0.81) occurred in April and May and decreased greatly in July when only
      postspawned fish with atretic ovaries occurred. Evidence indicates that L.
      bergylta are group-synchronous multiple spawners with spawning occurring in
      spring and peaking in May. A short resting period may occur between late summer
      and autumn when previtellogenic oocytes predominate and steroid levels are
      minimal.

PMID- 20701637
TI  - Changes in RNA, DNA, protein contents and growth of turbot Scophthalmus maximus
      larvae and juveniles.
AB  - The growth potential of turbot Scophthalmus maximus larvae and juveniles was
      studied using nucleic acid-based indices and protein variables. The experiment
      was carried out from 4 to 60 days post hatching (dph). A significant increase in
      instantaneous growth rate during metamorphosis and retarded growth rate during
      post-metamorphic phase were observed. Ontogenetic patterns of DNA, RNA and
      protein all showed developmental stage-specific traits. The RNA:DNA ratio
      decreased up to 12 dph, then increased rapidly till 19 dph and fluctuated until
      35 dph followed by a decline to the end. The RNA:DNA ratio was positively
      correlated with growth rate of juveniles during the post-metamorphic phase,
      whereas this ratio was not a sensitive indicator of growth during the pre
      metamorphic phase and metamorphosis. The protein:DNA ratio showed a similar
      tendency to the RNA:DNA ratio. Changes of DNA content and protein:DNA ratio
      revealed that growth of S. maximus performed mainly by hyperplasia from 4 to 12
      dph and hypertrophy until 21 dph during the pre-metamorphic larval phase. Growth
      was dominantly hypertrophical from the early- to mid-metamorphosing phase and
      hyperplastic thereafter. The results show that the DNA content and protein:DNA
      ratio can evaluate growth rates of larval and juvenile S. maximus on a cellular
      level.

PMID- 20701638
TI  - Residence time and drift patterns of larval June sucker Chasmistes liorus in the
      lower Provo River as determined by otolith microstructure.
AB  - Estimates of age derived from daily ring counts from otoliths and capture rates
      of larval June sucker Chasmistes liorus were used to determine the relationship
      between discharge rates of the Provo River and residence time and patterns of
      larval drift. During 1997, larval drift occurred over a 22 day period when
      discharge rates were low (mean +/-s.d. 3.2 +/- 0.0 m(3) s(-1)). In 1998, larval
      drift occurred in two separate events over a 40 day period. Discharge was higher
      during the first larval drift period (19 days; 24.8 +/- 1.3 m(3) s(-1)) and lower
      during the second larval drift period (17 days; 7.0 +/- 0.9 m(3) s(-1)). In 1997,
      no larval fish were collected at the lowermost transect on the Provo River
      (nearest Utah Lake), and few larvae >21 days of age were found. During the first
      drift period of 1998, larval C. liorus were collected at all transects, and mean
      age of larvae collected between upstream and downstream transects increased by c.
      7 days. During the second drift period of 1998, only a few were collected in the
      lowermost transects, and age did not increase with proximity to the lake.
      Patterns in catch and age distribution of larval C. liorus in the lower Provo
      River suggest that recruitment failure occurs during the larval drift period in
      years with insufficient discharge to transport larvae into the lake.

PMID- 20701639
TI  - Influence of moderate and severe hypoxia on the diurnal activity pattern of
      lesser sandeel Ammodytes tobianus.
AB  - The influence of prolonged moderate (c. 60% oxygen saturation) and severe hypoxia
      (c. 35% oxygen saturation) on the diurnal activity pattern of sandeel Ammodytes
      tobianus was examined. In moderate hypoxia, the emerging and burying rates were
      significantly higher compared to that in normoxia, whereas fewer fish (c. 10%)
      were present in the water column. In contrast, severe hypoxia resulted in twice
      as many or more fish being present in the water column compared to that in
      normoxia. The increased number of swimming fish was not just a relative change
      due to an effect from hypoxia treatment, but the behaviour of the fish was also
      changed. The summed activity (emerging plus burying events) was lower in severe
      hypoxia compared to normoxia except during hours of dim light. All fish were
      buried during night-time, regardless of treatment, with the exception of some in
      severe hypoxia during the first couple of hours of darkness.

PMID- 20701640
TI  - Size-dependent reproductive success of wild zebrafish Danio rerio in the
      laboratory.
AB  - Size-dependent reproductive success of wild zebrafish Danio rerio was studied
      under controlled conditions in the laboratory to further understand the influence
      of spawner body size on reproductive output and egg and larval traits. Three
      different spawner size categories attained by size-selective harvesting of the
      F(1)-offspring of wild D. rerio were established and their reproductive
      performance compared during a 5 day period. As to be expected, large females
      spawned more frequently and had significantly greater clutch sizes than small
      females. Contrary to expectations, small females produced larger eggs when
      measured as egg diameter with similar amounts of yolk compared to eggs spawned by
      large spawners. Eggs from small fish, however, suffered from higher egg mortality
      than the eggs of large individuals. Embryos from small-sized spawners also
      hatched later than offspring from eggs laid by large females. Larval standard
      length (L(S))-at-hatch did not differ between the size categories, but the
      offspring of the large fish had significantly larger area-at-hatch and greater
      yolk-sac volume indicating better condition. Offspring growth rates were
      generally similar between offspring from all size categories, but they were
      significantly higher for offspring spawned by small females in terms of L(S)
      between days 60 and 90 post-fertilization. Despite temporarily higher growth
      rates among the small fish offspring, the smaller energy reserves at hatching
      translated into lower condition later in ontogeny. It appeared that the influence
      of spawner body size on egg and larval traits was relatively pronounced early in
      development and seemed to remain in terms of condition, but not in growth, after
      the onset of exogenous feeding. Further studies are needed to explore the
      mechanisms behind the differences in offspring quality between large- and small
      sized spawners by disentangling size-dependent maternal and paternal effects on
      reproductive variables in D. rerio.

PMID- 20701641
TI  - Biological traits of rare males in the population of Carassius gibelio
      (Actinopterygii: Cyprinidae) from Lake Pamvotis (north-west Greece).
AB  - The gynogenetic population of Prussian carp Carassius gibelio in Lake Pamvotis
      (north-west Greece) included a small percentage of males (2-3%). Cytogenetic
      analysis revealed heterogeneity of the population at the ploidy level: all
      females were triploid (modal chromosome number 156-162 chromosomes) while the
      males were either triploid (modal number 156-158 chromosomes) or tetraploid
      (modal number 200-214 chromosomes). Morphometric analysis revealed significant
      differences in body shape among these three groups. The males were more slender
      than females, while the triploid males could be discriminated from the tetraploid
      by the morphology of their caudal peduncle. The males attained a significantly
      lower asymptotic standard length (L(S)) (25.04 cm) than females (29.75 cm) and
      had lower exponent b of the L(S) and mass relationship. Under laboratory
      conditions, intraspecific crossings of C. gibelio males with females could give
      viable all-female offspring; in comparison with goldfish Carassius auratus males,
      the fertility of the C. gibelio males was generally reduced but remained highly
      variable among individuals.

PMID- 20701642
TI  - Variation in fat content and fatty-acid composition of the Baltic herring Clupea
      harengus membras.
AB  - The fat content and fatty-acid profiles of herring, Clupea harengus membras, from
      the southern Baltic Sea varied depending on when (fishing season) and where
      (fishing grounds) the fish were caught as well as on their size and sex. The fat,
      protein and dry matter content and the fatty-acid profiles were assayed in C. h.
      membras muscle tissue. The changes observed in fatty-acid profiles were
      determined by factors such as specimen mass and fat content, which, in turn,
      depended on fishing season. This is explained by dietary differences between
      juvenile and older fish. Gonad maturation and spawning in the latter are also
      factors. The study results provide confirmation of the hypothesis that
      polyunsaturated fatty acids (PUFA), in particular docosahexaenoic acid (DHA) and
      eicosapentaenoic acid (EPA), play vital roles in the sexual maturation of C. h.
      membras.

PMID- 20701643
TI  - Growth and reproductive biology of the foxfish Bodianus frenchii, a very long
      lived and monandric protogynous hermaphroditic labrid.
AB  - Samples of the foxfish Bodianus frenchii, collected over reefs on the lower west
      and south coasts of Western Australia, contained individuals ranging up to 78
      years old. Although B. frenchii is far smaller than many other species within the
      Labridae, its maximum age is the greatest yet recorded for this highly speciose
      family and, together with Achoerodus gouldii, provides an example of a temperate
      hypsigenyine with exceptional longevity. Length and age compositions of females
      and males and the histological characteristics of gonads of a wide length range
      of individuals demonstrated that B. frenchii is a protogynous hermaphrodite.
      Furthermore, as, on both coasts, the length of the smallest male was greater than
      that at which all females had become mature, B. frenchii is a monandric
      protogynous hermaphrodite, i.e. all of its males are derived from functional
      females. Attainment of maturity by females is related more to length than age,
      whereas the reverse is true for sex change. On the basis of Schnute growth
      equations and length-to-body mass regression equations, the predicted length at
      age and body mass at length of fish on the south coast were greater than those on
      the west coast throughout life. Although B. frenchii spawns daily during the main
      spawning season, which extends from October to February on both coasts, its
      fecundity at any given length is substantially greater on the south than on the
      west coast. The more rapid growth of juveniles and earlier attainment of maturity
      by B. frenchii on the south coast than on the warmer west coast, together with
      maturation at a similar size on both coasts, run counter to the trends observed
      in many species and certain ecological theories regarding the relationships
      between life-cycle traits and latitude and temperature. The attainment by B.
      frenchii of a larger body length at age, of greater body mass at length and of
      greater fecundity at both length and body mass in fish on the south than on the
      west coast strongly suggests that conditions on the former, cooler coast are more
      favourable for this labrid, which belongs to a sub-genus whose other species
      typically live in cool, deep, temperate waters.

PMID- 20701644
TI  - Effects of a tropical cyclone on the distribution of hatchery-reared black-spot
      tuskfish Choerodon schoenleinii determined by acoustic telemetry.
AB  - The effects of a tropical cyclone on the distribution of hatchery-reared black
      spot tuskfish Choerodon schoenleinii were examined using acoustic telemetry. Nine
      fish were released in Urasoko Bay, Ishigaki Island, Japan, in September 2006, and
      another nine were released in June to July 2007, before a cyclone's passing
      through the area in September 2007. Data for the fish released in 2006 were used
      as the cyclone-inexperienced group to compare their distribution pattern to that
      of the 2007 cyclone-experienced group. Both groups of fish were monitored for up
      to 150 days. Of the nine fish in each group, four (44%) and two (22%) were
      monitored for over 150 days in the cyclone-inexperienced and the cyclone
      experienced groups, respectively. Three of the five fish that had settled in the
      monitoring area left the area within a few days of the cyclone event. To estimate
      the time of disappearance of the fish, maximum wind speed during a period of 7
      days (indicating the occurrence and intensity of the tropical cyclone), fish size
      and release year were evaluated as explanatory variables using a Cox proportional
      hazards model with Akaike's information criterion. The best predictive model
      included the effect of maximum wind speed. One fish that left the monitoring area
      displayed movement patterns related to strong winds, suggesting that wind
      associated strong currents swept the fish away. No relationships were found
      between the movement patterns of the other two fish and any physical
      environmental data. The daily detection periods of one of the two fish gradually
      decreased after the cyclone hit, and this fish eventually left the monitoring
      area within 3 days, suggesting that it shifted to a habitat outside the
      monitoring area. These results indicate that tropical cyclones have both direct
      and indirect effects on the distribution of hatchery-reared C. schoenleinii.

PMID- 20701645
TI  - The influence of tidal cycles and freshwater inflow on the distribution and
      movement of an estuarine resident fish Acanthopagrus butcheri.
AB  - Movement patterns and habitat utilization by black bream Acanthopagrus butcheri
      (Sparidae), an estuarine resident species, were investigated using acoustic
      telemetry in a small estuary on the east coast of Tasmania, Australia. Thirty
      four adult A. butcheri were tracked for periods of up to 187 days between August
      2005 and January 2006. Although able to tolerate a wide range of salinities, the
      fish spent most of the time within the upper and middle regions of the estuary,
      where brackish conditions dominated. The species exhibited extensive movements
      linked to tidal cycles, with small-scale upstream movements during incoming tides
      and downstream movements during out going tides. The extent of these movements
      was positively correlated with the tidal height difference between consecutive
      tidal peaks and troughs. Freshwater inflows and resultant changes in salinity
      also significantly influenced distribution and movement patterns. Fish moved
      downstream during the periods of heavy inflows, returning upstream as salinities
      increased to c. >10. During the peak of spawning period (November to December)
      fish moved into the upper region of the estuary, where they aggregated to spawn.
      Periodic increases in freshwater discharge, however, resulted in fish leaving the
      spawning grounds and moving downstream. Towards the end of the spawning season
      (January), the fish became more dispersed throughout the entire estuarine system.

PMID- 20701646
TI  - Habitat use and movement patterns of bull sharks Carcharhinus leucas determined
      using pop-up satellite archival tags.
AB  - Habitat use, movement and residency of bull sharks Carcharhinus leucas were
      determined using satellite pop-up archival transmitting (PAT) tags throughout
      coastal areas in the U.S., Gulf of Mexico and waters off the south-east U.S. From
      2005 to 2007, 18 fish (mean size = 164 cm fork length, L(F)) were tagged over all
      seasons. Fish retained tags for up to 85 days (median = 30 days). Based on
      geolocation data from initial tagging location to pop-off location, C. leucas
      generally travelled c. 5-6 km day(-1) and travelled an average of 143.6 km.
      Overall, mean proportions of time at depth revealed C. leucas spent the majority
      of their time in waters <20 m. They exhibited significant differences among
      depths but were not found at a particular depth regardless of diurnal period.
      Most fish occupied temperatures c. 32 degrees C with individuals found mostly
      between 26 and 33 degrees C. Geolocation data for C. leucas were generally poor
      and varied considerably but tracks for two individuals revealed long distance
      movements. One fish travelled from the south-east coast of the U.S. to coastal
      Texas near Galveston while another moved up the east coast of the U.S. to South
      Carolina. Data on C. leucas movements indicated that they are found primarily in
      shallower waters and tend to remain in the same location over long periods. While
      some individuals made large-scale movements over open ocean areas, the results
      emphasize the importance of the coastal zone for this species as potential
      essential habitat, particularly in areas of high freshwater inflow.

PMID- 20701647
TI  - Life history of a simultaneously hermaphroditic fish, Diplectrum formosum.
AB  - Sand perch Diplectrum formosum were collected in the Atlantic Ocean waters off
      the south-eastern U.S. for life history analyses between April 2001 and July 2004
      and ranged in size from 63 to 236 mm standard length (L(S)) and 0-8 years of age.
      Diplectrum formosum are simultaneous hermaphrodites that reach 50% sexual
      maturity at 12.2 months and 122.8 mm L(S) for testicular tissue and 13.6 months
      and 129.3 mm L(S) for ovarian tissue. The gonad contains ovarian and testicular
      tissue separated by a thin basement membrane, with no means of internal self
      fertilization. Spawning females were found between March and January with a peak
      of spawning activity in May and a realized spawning periodicity of 2 days,
      equivalent to a maximum of 168 spawning events per year. Fish with testicular
      tissue in spawning condition were obtained throughout the year in every month
      sampled with a maximum frequency between June and September. There were also
      trends indicating that testicular tissue was more likely to be in spawning
      condition in the presence of hydrated oocytes within the accessory structure.
      This may indicate the use of the accessory structure as a storage site for
      hydrated oocytes until a mate can be located.

PMID- 20701648
TI  - Lake-specific variation in growth, migration timing and survival of juvenile
      sockeye salmon Oncorhynchus nerka: separating environmental from genetic
      influences.
AB  - Time series on juvenile life-history traits obtained from sockeye salmon
      Oncorhynchus nerka were analysed to assess lake-specific environmental influences
      on juvenile migration timing, size and survival of fish from a common gene pool.
      Every year for the past two decades, O. nerka have been spawned at a hatchery
      facility, and the progeny released into two lakes that differ in average summer
      temperatures, limnological attributes and growth opportunities. Juveniles reared
      in the warmer, more productive Crosswind Lake were larger and heavier as smolts
      compared to those from the cooler, less productive Summit Lake and had higher in
      lake and subsequent marine survival. Crosswind Lake smolts migrated from the lake
      to sea slightly earlier in the season but the migration timing distributions
      overlapped considerably across years. Fry stocking density had a negative effect
      on smolt length for both lakes, and a negative effect on in-lake survival in
      Summit Lake. Taken together, the results revealed a strong effect of lake-rearing
      environment on the expression of life-history variation in O. nerka. The stocking
      of these lakes each year with juveniles from a single mixed-source population
      provided a large-scale reverse common-garden experiment, where the same gene pool
      was exposed to different environments, rather than the different gene pools in
      the same environment approach typical of evolutionary ecology studies. Other
      researchers are encouraged to seek and exploit similar serendipitous situations,
      which might allow environmental and genetic influences on ecologically important
      traits to be distinguished in natural or semi-natural settings.

PMID- 20701649
TI  - Gonadal development in a giant threatened reef fish, the humphead wrasse
      Cheilinus undulatus, and its relationship to international trade.
AB  - An opportunity arose to obtain humphead wrasse Cheilinus undulatus specimens
      between 2006 and 2009 from Indonesia, the major source and exporting country of
      this species, making study on its early gonad development possible for the first
      time. Protogynous hermaphroditism, previously proposed for this species, was
      confirmed in this study. Based on histological examination of 178 specimens,
      mainly <500 mm total length (L(T)) and ranging from 208 to 1290 mm L(T) (119.1 g
      to 43.0 kg whole body mass), the minimum body sizes for female and male sexual
      maturation were determined to be 650 and 845 mm L(T), respectively. Primary male
      development through juvenile sexual differentiation was not detected. A unique
      blind pouch, with a possible sperm storage function and associated with the
      testis, was reported for the first time in the Labridae. In Hong Kong retail
      markets, the global trading centre for this valuable species, live C. undulatus
      on sale for food were dominated by body sizes <500 mm L(T) between 1995 and 2009,
      reflecting an international trade largely focused on juveniles. In consideration
      of these findings, and given the threatened status of this species, management
      for C. undulatus capture and trade nationally and internationally are discussed
      with recommendations for ensuring sufficient spawning biomass in exploited
      populations and for sustainable trade.

PMID- 20701650
TI  - Quantification of ovarian follicles in bluefin tuna Thunnus thynnus by two
      stereological methods.
AB  - The numbers of different types of ovarian follicles (developing, degenerating and
      postovulatory follicles) were estimated in bluefin tuna Thunnus thynnus using two
      stereological procedures: the model-based method of Weibel & Gomez, which has
      become a tool of broad application in the quantification of oocytes in fishes,
      and the assumption-free 'disector' (sic) method of Sterio. The estimates of
      developing follicles (follicles containing lipid-stage, vitellogenic and
      migratory-nucleus oocytes) made by the model-based method tended to be lower than
      those obtained with the disector, though significant differences were not
      observed except for vitellogenic follicles. Counts of atretic follicles by the
      model-based method were higher than those made using the disector, the
      differences being remarkable between both techniques, particularly in the case of
      beta-atresia, where the statistical analysis indicated significantly unequal
      estimations with the two methods. In contrast, the amount of postovulatory
      follicles estimated by the disector, which would stand for the realized batch
      fecundity, was somewhat larger than that calculated with the model-based method.

PMID- 20701651
TI  - Widespread omnivory and low temporal and spatial variation in the diet of fishes
      in a hydrologically variable northern Australian river.
AB  - This article examines the trophic ecology of freshwater fishes (22 species in 15
      families) in a wet and dry tropical Australian river of high intra-annual and
      interannual hydrological variability. Seven major trophic groups were identified
      by cluster analysis; however, four food items (filamentous algae, chironomid
      larvae, Trichoptera larvae and Ephemeroptera nymphs) comprised almost half of the
      average diet of all species. The influence of species, fish size, spatial effects
      and temporal effects on food use was investigated using redundancy analysis.
      Size, time and space accounted for little of the perceived variation. Ontogenetic
      changes in diet were minor and limited to a few large species. Spatial variation
      in trophic composition of the fish assemblages reflected the effects of the
      Burdekin Falls and dam, a major geographic barrier, on species distributions.
      Little spatial variation in diet was detected after accounting for this
      biogeographical effect. Temporal variations in flow, although marked, had little
      effect on variations in fish diet composition due to the low temporal diversity
      of food resources in physically monotonous sand and gravel channels. Species
      identity accounted for<50% of the observed variation in food choice; omnivory and
      generalism were pronounced. The aquatic food web of the Burdekin River appears
      simple, supported largely by autochthonous production (filamentous and benthic
      microalgae, and to some extent, aquatic macrophytes). Allochthonous food
      resources appear to be unimportant. The generalist feeding strategies, widespread
      omnivory and absence of pronounced trophic segregation reported here for Burdekin
      River fishes may be common to variable and intermittent rivers of subtropical and
      tropical northern Australia with similar fish communities and may be a general
      feature of rivers of low habitat diversity and characterized by flow regimes that
      vary greatly both within and between years.

PMID- 20701652
TI  - Diet overlap among three sympatric African annual killifish species
      Nothobranchius spp. from Mozambique.
AB  - The diet patterns of three Nothobranchius species (N. furzeri, N. orthonotus and
      N. rachovii), small, short-lived annual killifish from temporary pools in African
      savannah were investigated. Four sites with contrasting fish density and water
      surface area were sampled in 2008 and 2009 in southern Mozambique. Stomach
      content analysis showed that all the species examined were generalists, with
      diets largely based on aquatic invertebrates. The same invertebrate prey
      categories were consumed by all three species, but their relative proportions
      varied across species. The largest species, N. orthonotus, showed the most
      distinct diet and consumed vertebrates (juvenile lungfish Protopterus annectens
      and larval Amphibia) and a relatively high proportion of Odonata, Coleoptera and
      Ephemeroptera larvae. The diet of the other two species (N. furzeri and N.
      rachovii) showed a stronger overlap, did not include vertebrates, but was rich in
      small crustaceans (Cladocera, Copepoda, Ostracoda and Conchostraca). Mosquito
      (Diptera) larvae formed only a negligible part of the diet of all the three
      species.

PMID- 20701654
TI  - Retraction. Gene duplication and functional evolution of Hox genes in fishes.

PMID- 20701653
TI  - Plasma cortisol and 11-ketotestosterone enzyme immunoassay (EIA) kit validation
      for three fish species: the orange clownfish Amphiprion percula, the orangefin
      anemonefish Amphiprion chrysopterus and the blacktip reef shark Carcharhinus
      melanopterus.
AB  - Commercially available enzyme immunoassay (EIA) kits were validated for measuring
      steroid hormone concentrations in blood plasma from three fish species: the
      orange clownfish Amphiprion percula, the orangefin anemonefish Amphiprion
      chrysopterus and the blacktip reef shark Carcharhinus melanopterus. A minimum of
      5 microl plasma was required to estimate hormone concentrations with both kits.
      These EIA kits are a simple method requiring minimal equipment, for measuring
      hormone profiles under field conditions.

PMID- 20701655
TI  - Confined displacement algorithm determines true and random colocalization in
      fluorescence microscopy.
AB  - The quantification of colocalizing signals in multichannel fluorescence
      microscopy images depends on the reliable segmentation of corresponding regions
      of interest, on the selection of appropriate colocalization coefficients, and on
      a robust statistical criterion to discriminate true from random colocalization.
      Here, we introduce a confined displacement algorithm based on image correlation
      spectroscopy in combination with Manders colocalization coefficients M1(ROI) and
      M2(ROI) to quantify true and random colocalization of a given florescence
      pattern. We show that existing algorithms based on block scrambling exaggerate
      the randomization of fluorescent patterns with resulting inappropriately narrow
      probability density functions and false significance of true colocalization in
      terms of p values. We further confine our approach to subcellular compartments
      and show that true and random colocalization can be analysed for model dendrites
      and for GABA(B) receptor subunits GABA(B)R1/2 in cultured hippocampal neurons.
      Together, we demonstrate that the confined displacement algorithm detects true
      colocalization of specific fluorescence patterns down to subcellular levels.

PMID- 20701656
TI  - Microstructural characterization of laser surface melted AISI M2 tool steel.
AB  - We describe the microstructure of Nd:YAG continuous wave laser surface melted
      high-speed steel, namely AISI M2, treated with different laser scanning speeds
      and beam diameters on its surface. Microstructural characterization of the
      remelted surface layer was performed using light optical and scanning electron
      microscopy and X-ray diffraction. The combination of the three techniques
      provided new insights into the substantial changes induced by laser surface
      melting of the steel surface layer. The advantage of the method is that it avoids
      the difficult and tedious work of preparing samples of this hard material for
      transmission electron microscopy, which is the technique normally used to study
      these fine microstructures. A melted zone with a dendritic structure and a
      partially melted zone with a heterogeneous cellular structure were observed.
      M(2)C carbides with different morphologies were identified in the resolidified
      surface layer after laser melting.

PMID- 20701657
TI  - An automated and highly efficient method for counting and measuring fluorescent
      foci in rod-shaped bacteria.
AB  - Direct measurements of cells from photo micrographs are becoming increasingly
      used when investigating the position and/or distribution of chromosomal loci in
      bacteria. In general, these measurements have been done manually, and without
      clear definition of how they are made. Here we present a procedure for
      standardizing the measurement of cell properties from phase contrast images.
      Furthermore, we present a program using these standardized methods that can
      measure the intracellular positions of fluorescent foci in bacterial cells faster
      and with more precision than manual measurement.

PMID- 20701658
TI  - Photometric calibration for quantitative spectral microscopy under transmitted
      illumination.
AB  - Over the past decade, there have been significant developments in the mechanisms
      for examination of biological and material samples. These developments exploit
      techniques in light microscopy to elucidate specific parts of cells and tissues,
      as well as inorganic particles. In recent years, spectral microscopy has become
      more prevalent for characterization of samples. Simultaneously, sensor technology
      has progressed as well and modern charge-coupled devices (CCD) cameras are now
      capable of achieving high spatial resolution and high sensitivity measurements of
      signals in the optical microscope. One major impediment in obtaining absolute
      quantitative information of imaged samples is the lack of automated photometric
      calibration mechanisms for spectral microscopes. In this paper, we present a
      methodology for achieving photometric calibration of an automated spectral
      imaging system targeted towards examination of biological samples. By acquiring
      spatial and spectral data simultaneously, spectral imaging allows one to exploit
      physical connections between a particle's morphology and its characteristic
      response to the optical spectrum. In composite biological material, the
      interpretation of the spectra is a complicated problem. This is because any light
      source and charge-coupled device camera used for data acquisition does not have a
      uniform illumination spectra and quantum efficiency, respectively, across the
      emitted light spectra. To balance the spectral response across individual
      wavelengths, our method modulates the exposure duration for the charge-coupled
      device camera during image acquisition. We present an image similarity based
      method to calibrate the system. Experiments to test the effectiveness of the
      calibration method under the various image similarity metrics are presented along
      with results to show the calibrated system's ability to accurately measure
      spectra based on the measured transmission profiles of optical filters.

PMID- 20701659
TI  - Enhanced angular current intensity from Schottky emitters.
AB  - Even though the Schottky emitter is a high-brightness source of choice for
      electron beam systems, its angular current intensity is substantially lower than
      that of thermionic cathodes, rendering the emitter impractical for applications
      that require high beam current. In this study, two strategies were attempted to
      enhance its angular intensity, and their experimental results are reported. The
      first scheme is to employ a higher extraction field for increasing the
      brightness. However, the tip shape transformation was found to induce undesirably
      elevated emission from the facet edges at high fields. The second scheme exploits
      the fact that the angular intensity is proportional to the square of the electron
      gun focal length [Fujita, S. & Shimoyama, H. (2005) Theory of cathode trajectory
      characterization by canonical mapping transformation. J. Electron Microsc. 54,
      331-343], which can be increased by scaling-up the emitter tip radius. A high
      angular current intensity (J(Omega) approximately 1.5 mA sr(-1)) was obtained
      from a scaled-up emitter. Preliminary performance tests were conducted on an
      electron probe-forming column by substituting the new emitter for the original
      tungsten filament gun. The beam current up to a few microamperes was achieved
      with submicron spatial resolution.

PMID- 20701660
TI  - Limitations of beam damage in electron spectroscopic tomography of embedded
      cells.
AB  - Elemental mapping in the energy filtering transmission electron microscope
      (EFTEM) can be extended into three dimensions (3D) by acquiring a series of two
      dimensional (2D) core-edge images from a specimen oriented over a range of tilt
      angles, and then reconstructing the volume using tomographic methods. EFTEM has
      been applied to imaging the distribution of biological molecules in 2D, e.g.
      nucleic acid and protein, in sections of plastic-embedded cells, but no
      systematic study has been undertaken to assess the extent to which beam damage
      limits the available information in 3D. To address this question, 2D elemental
      maps of phosphorus and nitrogen were acquired from unstained sections of plastic
      embedded isolated mouse thymocytes. The variation in elemental composition,
      residual specimen mass and changes in the specimen morphology were measured as a
      function of electron dose. Whereas 40% of the total specimen mass was lost at
      doses above 10(6) e(-)/nm(2), no significant loss of phosphorus or nitrogen was
      observed for doses as high as 10(8) e(-)/nm(2). The oxygen content decreased from
      25 + or - 2 to 9 + or - 2 atomic percent at an electron dose of 10(4) e(-)/nm(2),
      which accounted for a major component of the total mass loss. The specimen
      thickness decreased by 50% after a dose of 10(8) e(-)/nm(2), and a lateral
      shrinkage of 9.5 + or - 2.0% occurred from 2 x 10(4) to 10(8) e(-)/nm(2). At
      doses above 10(7) e(-)/nm(2), damage could be observed in the bright field as
      well in the core edge images, which is attributed to further loss of oxygen and
      carbon atoms. Despite these artefacts, electron tomograms obtained from high
      pressure frozen and freeze-substituted sections of C. elegans showed that it is
      feasible to obtain useful 3D phosphorus and nitrogen maps, and thus to reveal
      quantitative information about the subcellular distributions of nucleic acids and
      proteins.

PMID- 20701661
TI  - Scintillation SE detector for variable pressure scanning electron microscopes.
AB  - We present results obtained with a new scintillation detector of secondary
      electrons for the variable pressure scanning electron microscope. A detector
      design is based on the positioning of a single crystal scintillator within a
      scintillator chamber separated from the specimen chamber by two apertures. This
      solution enables us to decrease the pressure to several Pa in the scintillator
      chamber while the pressure in the specimen chamber reaches values of about 1000
      Pa (7.5 Torr). Due to decreased pressure, we can apply a potential of the order
      of several kV to the scintillator, which is necessary for the detection of
      secondary electrons. Simultaneously, the two apertures at appropriate potentials
      of the order of several hundreds of volts create an electrostatic lens that
      allows electrons to pass from the specimen chamber to the scintillator chamber.
      Results indicate a promising utilization of this detector for a wide range of
      specimen observations.

PMID- 20701662
TI  - Domain structures of ultrafine grained ferromagnets achieved by severe plastic
      deformation or melt quenching.
AB  - Lorentz electron microscopy was used to analyse the domain structure in some
      ferromagnets having an ultrafine grained structure produced by high pressure
      torsion (pure Ni, Fe, Co, Mn(55.5)Al(45.5) C(0.5)) and by melt quenching
      (Fe(83)Nd(13)B(4)). For low anisotropy ferromagnets (Ni, Fe, Co), it has been
      established that the domain structure does not depend strongly on grain size. In
      high anisotropy ferromagnets alloy (Mn(55.5)Al(45.5) C(0.5) and
      Fe(83)Nd(13)B(4)), grain refinement causes changes in the domain structure
      configuration and affects the magnetization mechanism.

PMID- 20701663
TI  - Electron back-scattering diffraction (EBSD) measurements of antigorite lattice
      preferred orientations (LPO).
AB  - Lattice preferred orientations of serpentines induce a strong anisotropy of
      various properties in serpentine bearing-rocks. Lattice preferred orientations
      had so far been obtained only by X-ray diffraction techniques. We have applied
      electron back-scattering diffraction to the measurement of the lattice preferred
      orientations of antigorite in a naturally deformed high-pressure serpentinite.
      This technique is very sensitive to sample preparation that can lead to surface
      amorphization in the case of serpentine. A polishing procedure is described that
      avoids amorphization and allows accurate electron back-scattering diffraction
      measurements with optimized experimental conditions in a variable pressure
      scanning electron microscope. Results indicate that deformation leads to lattice
      preferred orientations characterized by extremely strong c-axis clustering
      perpendicular to the foliation, as expected for a layered silicate. In the
      foliation plane, a significant clustering of the a-axis is observed and
      tentatively attributed to intracrystalline deformation mechanisms. These data
      suggest that antigorite deforms mostly by gliding along the basal plane of the
      layered phyllosilicate structure, but that gliding may occur along directions
      favouring a-axis alignment. Electron back-scattering diffraction appears to be a
      reliable method for determining phyllosilicate lattice preferred orientations in
      deformed rocks, with potential applications for determining anisotropy of
      properties like seismic velocities or thermal and electrical conductivities.

PMID- 20701664
TI  - Low temperature and anhydrous electron microscopy techniques to observe the
      infection process of the bacterial pathogen Xanthomonas fragariae on strawberry
      leaves.
AB  - Preserving the structural arrangement of the components of a bacterial infection
      process within a plant for microscopy study is a technical challenge because of
      the different requirements of each component for optimal preservation and
      visualization. We used low temperature scanning electron microscopy (cryo-SEM),
      anhydrous fixation at ambient temperature and freeze-substitution for
      transmission electron microscopy to examine fractured and sectioned strawberry
      leaves infected with Xanthomonas fragariae. Cryo-SEM images of fractured samples
      showed the bacterial colonization of mesophyll air spaces in the leaf, limited by
      the vascular bundles and the orientation and packing of bacteria in extracellular
      polysaccharide. Transmission electron microscopy of samples fixed using osmium
      tetroxide dissolved in FC-72 solvent at ambient temperature showed that the
      entire plant/bacteria/extracellular polysaccharide system was preserved in situ,
      and showed plasmolysis of mesophyll cells and disruption of organelles. In freeze
      substitution samples, osmium tetroxide in FC-72 solvent gave superior
      preservation of the extracellular polysaccharide as compared to a conventional
      cocktail. In addition, strands believed to be xanthan were preferentially
      contrasted to show their density and orientation around the bacterial cells. We
      conclude that anhydrous fixation using osmium tetroxide in FC-72 at ambient
      temperature gave the best preservation of the entire system, and freeze
      substitution using this same fixative enhanced the visualization of strands in
      the biofilm.

PMID- 20701665
TI  - Expression of receptor activator of NF-kappaB ligand and osteoprotegerin in
      peripheral giant cell granulomas of the jaws.
AB  - BACKGROUND: Peripheral giant cell granuloma is a tumor of the jaw characterized
      by the presence of multinucleated giant cells and mononuclear cells within a
      fibrous stroma. These lesions are considered to be of a reactive nature rather
      than neoplastic. Although peripheral giant cell granulomas is a well-described
      clinical entity, little is known on its pathogenesis. The aim of this study was
      to investigate the receptor activator of NF-kappaB ligand (RANKL) and
      osteoprotegerin (OPG) expression and immunolocalization in giant cell granulomas.
      METHODS: RANKL and OPG protein expression was evaluated in 22 peripheral giant
      cell granulomas samples, by means of immunohistochemistry. Staining was evaluated
      semi-quantitatively, according to the extent and intensity of the stain. RESULTS:
      RANKL was expressed in all cases with a cytoplasmic staining pattern, whereas OPG
      expression was detected in 21 of the 22 cases examined. Active multinucleated
      giant cells exhibited intense immunoreactivity for both proteins. CONCLUSION:
      RANKL and OPG are expressed in peripheral giant cell granulomas of the jaw in a
      manner supporting the osteoclastic nature of giant cells whereas the possible
      osteoclastic lineage of stromal monocytes remains ambiguous.

PMID- 20701666
TI  - Proliferative, apoptotic and angiogenic potentials in jaws and long bones
      osteosarcomas: a comparative immunohistochemical study.
AB  - BACKGROUND: Osteosarcomas (OS) of the jaws are uncommon lesions that represent
      less than 10% of all skeletal OS. It has a behavioral pattern which is less
      aggressive than their long bones counterparts. This study performed an
      immunohistochemical comparison between jaws and long bones OS. METHODS: The study
      involved 15 jaws and 15 long bones OS tissue samples for the period from 1986 to
      2005. Age, sex, histologic subtypes and grades were recognized. The samples were
      immunohistochemically stained with monoclonal antibodies to Ki-67, P53 and
      vascular endothelial growth factor (VEGF). RESULTS: The mean age of the patients
      with jaw OS was a decade higher than that of long bones OS. A slight male
      predominance in jaw OS was found (1.14:1), which was more pronounced in long
      bones OS (2:1). The chondroblastic subtype was the predominant in jaws (66.66%),
      whereas (60%) of long bones OS were of osteoblastic subtype. The Ki-67 labeling
      index and the VEGF expression were significantly higher in long bones as compared
      with jaws OS, whereas there was no significant difference regarding the P53
      expression between jaws and long bones OS. CONCLUSIONS: Jaws and long bones OS
      bear a comparable cell cycle dysregulation when quantified with P53
      immunostaining, whereas the long bones OS have a higher proliferative and
      angiogenic capacity than their jaw counterparts when evaluated with Ki-67 and
      VEGF immunoexpressions respectively.

PMID- 20701667
TI  - Different therapeutic strategies for burning mouth syndrome: preliminary data.
AB  - BACKGROUND: To compare different therapeutic supportive approaches in patients
      with burning mouth syndrome. A prospective study was carried out for this
      purpose. MATERIALS AND METHODS: The study involved 56 patients with burning mouth
      syndrome. They were randomly assigned to treatment with capsaicin, alpha-lipoic
      acid or lysozyme-lactoperoxidase (test drugs) or boric acid (control group).
      Symptoms were scored after 60 days treatment and 60 days after drug
      discontinuation. RESULTS: At the end of the treatment period, there was a
      significant reduction in the symptom scores of all of the patients who received
      the test drugs (P<0.01), and at the end of the follow-up period in the test
      groups as a whole (P<0.01); the reduction was not significant when considering
      each test group separately after the treatment period. All of the treatments were
      more effective than boric acid and there was no significant difference in the
      symptom scores of the control group at either of the study time-points.
      CONCLUSIONS: Our results demonstrate the similar effectiveness of capsaicin and
      alpha-lipoic acid in controlling the symptoms of burning mouth syndrome. Lysozyme
      lactoperoxidase may be effective in the supportive care of BMS patients with
      xerostomia. The transitory effect observed after discontinuing drug
      administration justifies the use of prolonged therapy in chronically affected
      patients.

PMID- 20701668
TI  - Assessment and further development of RDC/TMD Axis II biobehavioural instruments:
      a research programme progress report.
AB  - A symposium was held in Toronto, 2008, in which research progress regarding the
      biobehavioural dimension of the Research Diagnostic Criteria for
      Temporomandibular Disorders (RDC/TMD) was presented. An extended workshop was
      held in April 2009 in which further recommendations were made from an expert
      panel, using the 2008 symposium material as a base. This paper is a summary of
      the 2008 symposium proceedings with elaborations based on further developments.
      Seven studies were conducted between 2001 and 2008, in which the following were
      investigated: (i) basic properties of Axis II instruments, (ii) reliability and
      criterion validity of Axis II instruments, (iii) expansion of predictors, (iv)
      metric equivalence of the depression and non-specific physical symptoms subscales
      in the RDC/TMD, (v) laboratory investigation of oral behaviours, (vi) field data
      collection of oral behaviours, and (vii) functional limitation of the jaw.
      Methods and results for each of these studies are described. Based on the results
      of these studies that have been published, as well as the direction of interim
      results from the few studies that await completion and publication, the
      biobehavioural domain of the RDC/TMD, as published in 1992, is reliable and
      valid. These results also provide strong evidence supporting the future growth of
      the biobehavioural domain as the RDC/TMD matures into subsequent protocols for
      both clinical and research applications.

PMID- 20701669
TI  - Differential regulation of chemokine expression by estrogen in human periodontal
      ligament cells.
AB  - BACKGROUND AND OBJECTIVE: Estrogen modulates inflammatory responses, but the
      mechanisms involved have not yet been identified. Periodontal ligament (PDL)
      cells produce chemokines (a group of chemoattractant molecules that recruit
      leukocytes) and it has been suggested that estrogen modulates periodontal
      inflammation by regulating the expression of chemokines by PDL cells. Therefore,
      the objectives of this study were to investigate the regulation of chemokine
      ligand 2 [CCL2/monocyte chemoattractant protein 1 (MCP-1)], chemokine ligand 3
      [CCL3/macrophage inflammatory protein-1alpha (MIP-1alpha)] and chemokine ligand 5
      (CCL5/RANTES) by estrogen in human PDL cells. MATERIAL AND METHODS: PDL cells
      were obtained from the PDL of premolars, extracted for orthodontic reasons, from
      two boys and two girls (16 and 17 years of age). PDL cell CCL2, CCL3 and CCL5
      mRNA transcripts were determined by quantitative real-time PCR. The
      concentrations of CCL2, CCL3 and CCL5 proteins were determined by ELISAs.
      RESULTS: Treatment with 0.5 MUg/mL of lipopolysaccharide (LPS, from Escherichia
      coli) + 100 nm 17beta-estradiol (E(2) ) for 24 h reduced the expression of CCL3
      mRNA by about 40% compared to PDL cells treated with LPS alone. Attenuation of
      CCL3 mRNA was not associated with a decrease in CCL3 protein within 48 h,
      suggesting a slow turnover of the CCL3 protein. Interindividual differences in
      the effects of E(2) on CCL5 mRNA expression were observed. E(2) (100 nm)
      increased the expression of CCL5 by 40-60% in PDL cells derived from two subjects
      but reduced the expression of CCL5 by about 30% in cells from another subject.
      CCL2 mRNA and CCL2 protein were highly expressed, but not regulated by E(2) .
      Similar data were observed in cells obtained from both boys and girls.
      CONCLUSION: Regulation, by estrogen, of chemokine expression in PDL cells shows a
      complex pattern involving the down-regulation as well as the up-regulation of
      chemokines, suggesting that estrogen exerts both anti-inflammatory and
      proinflammatory effects through these mechanisms.

PMID- 20701670
TI  - Effect of bisphosphonates on human gingival fibroblast production of mediators of
      osteoclastogenesis: RANKL, osteoprotegerin and interleukin-6.
AB  - BACKGROUND AND OBJECTIVE: Osteonecrosis of the jaw (ONJ) is associated with
      bisphosphonate (BP) therapy. BPs alter osteoblast production of mediators of
      osteoclastogenesis, including interleukin (IL)-6, RANKL and osteoprotegerin
      (OPG), a RANKL antagonist. This can inhibit bone turnover and lead to necrosis.
      There is little information on the contribution of gingival fibroblasts, near
      bone-resorption sites, to the IL-6/RANKL/OPG network, the effects of BPs, or
      fibroblast involvement in ONJ pathogenesis. Therefore, the objective of this
      study was to determine the effects of alendronate and pamidronate on the
      constitutive production, or the lipopolysaccharide (LPS)- or IL-1beta-stimulated
      production, of IL-6, RANKL and OPG by human gingival fibroblasts. MATERIAL AND
      METHODS: Human gingival fibroblasts were derived from explants obtained from
      healthy individuals with noninflamed gingiva. Cytotoxicity was determined by
      measuring the activity of a mitochondrial enzyme. Fibroblasts were pre-incubated
      or not with BPs (0.01 nm-1 MUm), then incubated or not with LPS or IL-1beta. The
      concentrations of IL-6, OPG and RANKL were measured using ELISA. Data were
      analyzed using analysis of variance (ANOVA) and Scheffe's F procedure. RESULTS:
      LPS and BPs were not cytotoxic. The cells produced IL-6, OPG and RANKL, all of
      which were stimulated by IL-1beta or LPS (p <= 0.04). BPs generally increased the
      production of IL-6 and OPG (p <= 0.04) and decreased the production of RANKL (p
      <= 0.02). BPs generally further increased the production of LPS- or IL-1beta
      stimulated IL-6 (p <= 0.04) and had no effect on, or further increased, the
      production of LPS- or IL-1beta-stimulated OPG (p <= 0.04). BPs decreased the
      production of LPS- or IL-1beta-stimulated RANKL (p <= 0.04) and decreased
      constitutive, LPS-stimulated and IL-1beta-stimulated RANKL/OPG ratios (p <=
      0.02). CONCLUSION: The action of alendronate and pamidronate on human gingival
      fibroblasts, through altering the production of RANKL and OPG, appears to
      contribute to a microenvironment favoring the inhibition of bone resorption and
      ONJ.

PMID- 20701671
TI  - Expression of cytokines in the gingival crevicular fluid and serum from patients
      with inflammatory bowel disease and untreated chronic periodontitis.
AB  - BACKGROUND AND OBJECTIVE: Previous studies have reported an increased
      prevalence/severity of chronic periodontitis in patients with inflammatory bowel
      disease. However, the pathogenesis of periodontal lesions in such patients has
      not been characterized. The aim of this pilot study was to characterize the
      pattern of expression of cytokines in the gingival crevicular fluid and serum
      from patients with untreated chronic periodontitis and Crohn's disease,
      ulcerative colitis and systemically healthy controls. MATERIAL AND METHODS:
      Fifteen patients with Crohn's disease, 15 patients with ulcerative colitis and 15
      controls participated in the study. All subjects had been diagnosed with
      untreated chronic periodontitis. The clinical parameters evaluated were clinical
      attachment loss, bleeding on probing and percentage of plaque. The gingival
      crevicular fluid was sampled from four shallow and four deep periodontal sites of
      each patient. The concentrations of the cytokines interleukin (IL)-1beta, IL-4,
      IL-6, IL-10, IL-12p40, IL-12p70, interferon-gamma and tumor necrosis factor-alpha
      were measured using a commercially available Lincoplex kit and the concentration
      of IL-18 was measured using an ELISA. RESULTS: Multiple comparisons analysis
      showed that clinical attachment loss, bleeding on probing, percentage of plaque
      and volume of gingival crevicular fluid were similar across the groups. The
      concentration of IL-4 in the gingival crevicular fluid differed significantly
      between groups in shallow sites (p = 0.046), with higher values found for the
      controls. In serum, the concentration of IL-18 was also significantly different
      between groups, with lower values found for controls (p = 0.018). CONCLUSION:
      This study showed a higher concentration of IL-18 in serum, but not in the
      gingival crevicular fluid, from periodontitis patients with Crohn's disease or
      ulcerative colitis compared with controls. The expression of cytokines was
      similar in the gingival crevicular fluid from patients with untreated chronic
      periodontitis who also had Crohn's disease or ulcerative colitis and in
      systemically healthy controls with untreated chronic periodontitis.

PMID- 20701675
TI  - Prospective follow-up of female sexual function after vaginal surgery for pelvic
      organ prolapse using transobturator mesh implants.
AB  - INTRODUCTION: Although the use of transobturator mesh implants for pelvic organ
      prolapse repair has been shown to be safe and effective, concern exists that the
      presence of prosthetic material in the vagina may adversely affect sexual
      function. AIM: To evaluate the impact of transobturator mesh implantation on
      sexual function using validated questionnaire. MAIN OUTCOME MEASURES: Female
      Sexual Function Index (FSFI), a validated 19-item questionnaire that assesses six
      domains of sexual function (desire, arousal, lubrication, orgasm, satisfaction,
      and pain), was used. The questionnaire was administered preoperatively, and at 3,
      6, 12, and 24 months postoperatively. Clinical data were also recorded at each
      time point. METHODS: Prospective nonrandomized study including 96 women with
      pelvic organ prolapse (cystocele, rectocele, vault prolapse). Transvaginal
      anterior or posterior wall repair using transobturator mesh implants with or
      without concomitant transobturator sling procedure. RESULTS: Mean age was 51.4 +/
      5.2 years. Mean operating time was 47.6 +/- 23.4 minutes, and the mean
      hospitalization period was 3.8 +/- 1.6 days. After initial decrease during the
      first 3 months, patients experienced a steady improvement in their sexual
      function. At 24 months postoperatively, the total mean FSFI score reached
      significantly higher values compared to the baseline (P = 0.023). Furthermore,
      pain-free intercourse improved during the follow-up reaching mean score of 4.27
      +/- 0.79 (P < 0.05) after 2 years. Pelvic floor examination at 2 years follow-up
      showed excellent surgical results with only 3.1% of the patients presenting with
      stage II vaginal wall prolapse. CONCLUSIONS: Surgical repair of symptomatic
      pelvic organ prolapse using mesh implants results in improvement of major
      parameters of sexual function. A worsening in pain with intercourse during the
      initial months postoperatively lessens after 3 months as healing is completed.

PMID- 20701676
TI  - When are sexual difficulties distressing for women? The selective protective
      value of intimate relationships.
AB  - INTRODUCTION: Recent studies have shown that sexual functioning and sexually
      related personal distress are weakly related in women, with only a minority of
      sexual difficulties resulting in significant levels of distress. However, there
      has been little systematic research to date on which factors moderate the
      relationship between sexual functioning and sexual distress. AIM: To assess the
      degree to which relational intimacy and attachment anxiety moderate the
      association between sexual functioning and sexual distress in college-age women.
      METHODS: Two hundred women (mean age=20.25) completed surveys assessing sexual
      functioning, relational intimacy, attachment anxiety, and sexual distress. MAIN
      OUTCOME MEASURES: Participants completed the Sexual Satisfaction Scale for Women,
      the Female Sexual Function Index, the Dimensions of Relationship Quality Scale,
      and the Revised Experiences in Close Relationships Measure of Adult Romantic
      Attachment. RESULTS: Relational intimacy and attachment anxiety moderated the
      association between multiple aspects of sexual functioning and sexual distress.
      For lubrication and sexual pain, functioning was more strongly associated with
      distress in low-intimacy vs. high-intimacy relationships, but only for women with
      high levels of attachment anxiety. Results regarding desire were mixed and
      neither intimacy nor attachment anxiety interacted with subjective arousal or
      orgasm in predicting distress. CONCLUSION: Both relational intimacy and
      attachment anxiety are important moderators of the association between sexual
      functioning and subjective sexual distress in women. Theoretical and practical
      implications are discussed.

PMID- 20701677
TI  - Woman and partner-perceived partner responses predict pain and sexual
      satisfaction in provoked vestibulodynia (PVD) couples.
AB  - INTRODUCTION: Provoked vestibulodynia (PVD) is a highly prevalent vulvovaginal
      pain condition that results in significant sexual dysfunction, psychological
      distress, and reduced quality of life. Although some intra-individual
      psychological factors have been associated with PVD, studies to date have
      neglected the interpersonal context of this condition. AIM: We examined whether
      partner responses to women's pain experience-from the perspective of both the
      woman and her partner-are associated with pain intensity, sexual function, and
      sexual satisfaction. METHODS: One hundred ninety-one couples (M age for
      women=33.28, standard deviation [SD]=12.07, M age for men=35.79, SD=12.44) in
      which the woman suffered from PVD completed the spouse response scale of the
      Multidimensional Pain Inventory, assessing perceptions of partners' responses to
      the pain. Women with PVD also completed measures of pain, sexual function, sexual
      satisfaction, depression, and dyadic adjustment. MAIN OUTCOME MEASURES: Dependent
      measures were women's responses to: (i) a horizontal analog scale assessing the
      intensity of their pain during intercourse; (ii) the Female Sexual Function
      Index; and (iii) the Global Measure of Sexual Satisfaction Scale. RESULTS:
      Controlling for depression, higher solicitous partner responses were associated
      with higher levels of women's vulvovaginal pain intensity. This association was
      significant for partner-perceived responses (beta=0.29, P<0.001) and for woman
      perceived partner responses (beta=0.16, P=0.04). After controlling for sexual
      function and dyadic adjustment, woman-perceived greater solicitous partner
      responses (beta=0.16, P=0.02) predicted greater sexual satisfaction. Partner
      perceived responses did not predict women's sexual satisfaction. Partner
      responses were not associated with women's sexual function. CONCLUSIONS: Findings
      support the integration of dyadic processes in the conceptualization and
      treatment of PVD by suggesting that partner responses to pain affect pain
      intensity and sexual satisfaction in affected women.

PMID- 20701678
TI  - Prevalence of erectile dysfunction in systolic heart failure patients in a
      developing country: Tbilisi, Georgia, Eastern Europe.
AB  - INTRODUCTION: In the past decade, there has been an increasing amount of
      published information regarding erectile dysfunction (ED) and heart failure (HF)
      in economically advanced, westernized populations. However, there is a paucity of
      data regarding ED and HF in developing countries. The country of Georgia is
      categorized as a lower-middle-income country (LMIC) with an emerging and
      developing economy. AIM: To examine the prevalence of ED in patients with HF from
      a developing and LMIC and assess the association with depression. METHODS: We
      conducted an observational, cross-sectional study that included male patients 18
      years of age or older with an ejection fraction <=40% by echocardiogram in a
      heart failure disease management program in Tbilisi, Georgia. The Sexual Health
      Inventory for Men (SHIM) survey was used to categorize men according to degree of
      ED. Baseline clinical characteristics known to be associated with ED, such as New
      York Heart Association functional classification, were also documented. MAIN
      OUTCOME MEASURES: The SHIM survey and the nine-question Patient Health
      Questionnaire. RESULTS: The prevalence of ED was found to be 61.7%. Patients with
      ED were generally older, had more peripheral vascular disease, and had greater
      levels of depression than those without ED. CONCLUSIONS: There is a high
      prevalence of ED in patients with HF living in Tbilisi, Georgia. In comparison to
      previously published data on HF populations, our Georgian population showed
      lesser degrees of ED. More research is needed to better explain the causality for
      lower prevalence of ED, but explanations may include lower degrees of diabetes
      and aspects of treatment such as beta-blocker medication. Health care providers
      in LMICs should screen all of their male HF patients for ED and provide
      appropriate therapy.

PMID- 20701679
TI  - Human dendritic cells expressing hepatitis C virus core protein display
      transcriptional and functional changes consistent with maturation.
AB  - Hepatitis C virus (HCV) causes a chronic liver infection, which may result in
      cirrhosis and hepatocellular carcinoma. Impairment of the maturation process in
      dendritic cells (DCs) may be one of the mechanisms responsible for immune evasion
      of HCV. The core and NS3 proteins are among the most conserved HCV proteins and
      play a key role in viral clearance. To evaluate the effects of these proteins on
      DCs, monocyte-derived immature DCs (iDCs) were transfected with in vitro
      transcribed (IVT) HCV core or NS3 RNA and treated with maturation factors.
      Neither core nor NS3 had an inhibitory effect on DC maturation; however,
      transfection of iDCs with IVT core RNA appeared to result in changes compatible
      with maturation. To investigate this in more detail, the transcriptional profiles
      of iDCs transfected with IVT core, NS3 or green fluorescent protein (GFP) RNA
      were examined using a DC-specific membrane array. Of the 288 genes on the array,
      46 genes were distinctively up- or down-regulated by transfection with IVT core
      RNA in comparison with NS3 or GFP RNA treatments. Forty-two of these genes are
      involved in DC maturation. The effects of core on maturation of iDCs were
      confirmed with a significant increase in surface expression of CD83 and HLA-DR, a
      reduction of phagocytosis, as well as an increase in proliferation and IFN-gamma
      secretion by T cells in a mixed lymphocyte reaction assay. These results show
      that HCV core does not have an inhibitory effect on human DC maturation, but
      could be a target for the immune system.

PMID- 20701681
TI  - An integrative approach to species discovery in odonates: from character-based
      DNA barcoding to ecology.
AB  - Modern taxonomy requires an analytical approach incorporating all lines of
      evidence into decision-making. Such an approach can enhance both species
      identification and species discovery. The character-based DNA barcode method
      provides a molecular data set that can be incorporated into classical taxonomic
      data such that the discovery of new species can be made in an analytical
      framework that includes multiple sources of data. We here illustrate such a
      corroborative framework in a dragonfly model system that permits the discovery of
      two new, but visually cryptic species. In the African dragonfly genus Trithemis
      three distinct genetic clusters can be detected which could not be identified by
      using classical taxonomic characters. In order to test the hypothesis of two new
      species, DNA-barcodes from different sequence markers (ND1 and COI) were combined
      with morphological, ecological and biogeographic data sets. Phylogenetic analyses
      and incorporation of all data sets into a scheme called taxonomic circle highly
      supports the hypothesis of two new species. Our case study suggests an analytical
      approach to modern taxonomy that integrates data sets from different disciplines,
      thereby increasing the ease and reliability of both species discovery and species
      assignment.

PMID- 20701682
TI  - Cultivated and weedy rice interactions and the domestication process.
AB  - Examining the targets of selection in crop species and their wild and weedy
      relatives sheds light on the evolutionary processes underlying differentiation of
      cultivars from progenitor lineages. On one hand, human-mediated directional
      selection in crops favours traits associated with the streamlining of
      controllable and predictable monoculture practices alongside selection for
      desired trait values. On the other hand, natural selection in wild and especially
      weedy relatives presumably favours trait values that increase the probability of
      escaping eradication. Gene flow between crops and wild species may also counter
      human-mediated selection, promoting the evolution and persistence of weedy forms.
      In this issue, two studies from a group of collaborators examine diversity and
      divergence patterns of genes underlying two traits associated with red rice
      (Oryza sp.), the conspecific relative of cultivated rice (Oryza sativa) that is a
      non-native weed (see Fig. 1). In the first study by Gross et al. (2010), genetic
      variation in the major gene underlying the hallmark red pigmentation
      characterizing most weedy rice (Rc) is found to have a pattern consistent with
      non-reversion from U.S. cultivated rice (i.e. the cultivar did not 'go feral').
      This suggests that U.S. weedy rice is not an escaped lineage derived from U.S.
      cultivated rice populations; weedy rice likely differentiated prior to the
      selective sweep occurred in this gene within cultivated rice populations. Using
      the major seed shattering locus sh4 gene and the neighbouring genomic region,
      Thurber et al. (2010) track the molecular evolutionary history of the high
      shattering phenotype, a trait contributing dramatically to the success of crop
      selection in cultivated rice as well as the persistence and expansion of weedy
      red rice. In this study, the shared fixation of a sh4 mutation in both cultivated
      rice and weedy rice indicates that weedy rice arose subsequent to the strong
      selective sweep leading to significant reduction in seed shattering in cultivated
      rice.

PMID- 20701683
TI  - Landscape genetics of alpine Sierra Nevada salamanders reveal extreme population
      subdivision in space and time.
AB  - Quantifying the influence of the landscape on the genetic structure of natural
      populations remains an important empirical challenge, particularly for poorly
      studied, ecologically cryptic species. We conducted an extensive microsatellite
      analysis to examine the population genetics of the southern long-toed salamander
      (Ambystoma macrodactylum sigillatum) in a naturally complex landscape. Using
      spatially explicit modelling, we investigated the influence of the Sierra Nevada
      topography on potential dispersal corridors between sampled populations. Our
      results indicate very high-genetic divergence among populations, high within-deme
      relatedness, and little evidence of recent migration or population admixture. We
      also discovered unexpectedly high between-year genetic differentiation (F(ST))
      for breeding sites, suggesting that breeding groups vary over localized space and
      time. While environmental factors associated with high-elevation montane habitats
      apparently play an important role in shaping population differentiation,
      additional, species-specific biological processes must also be operating to
      account for observed deviations from temporal, among-year panmixia. Our study
      emphasizes the population-level insights that can be gained from high-density
      sampling in space and time, and the highly substructured population biology that
      may characterize amphibians in extreme montane habitats.

PMID- 20701684
TI  - Ventriculitis caused by Aspergillus fumigatus in a child with central nervous
      system tuberculosis.

PMID- 20701685
TI  - Mycetoma caused by Phaeoacremonium parasiticum--a case confirmed with B-tubulin
      sequence analysis.

PMID- 20701686
TI  - Emerging excellence in neurogastroenterology and motility research in the Arabian
      Peninsula.

PMID- 20701687
TI  - Detailed knowledge of cellular expression of G protein-coupled receptors in the
      human enteric nervous system is essential for understanding their diverse
      actions.
AB  - G protein-coupled receptors (GPCRs) comprise a large and diverse superfamily of
      transmembrane receptors that mediate the functions of an extraordinarily large
      number of extracellular ligands. They control many major physiological processes
      and are involved in diverse pathological processes, including gastrointestinal
      diseases. G protein-coupled receptors are one of the most targeted classes in
      pharmaceutical drug research. At present, much of our knowledge concerning the
      expression, distribution and function of GPCRs in the gut has been gleaned from
      studies performed in experimental models. Data obtained in the human digestive
      tract, especially in the enteric nervous system, are sparse and incomplete,
      although enteric neurons have a key position in almost all physiological and
      pathophysiological processes in the gut. Knowledge of cellular distribution of
      GPCRs, of regional differences in GPCR expression, and of altered GPCR expression
      during pathophysiological conditions in the human gut, will lead to a better
      understanding of GPCR activity, but will also contribute to the development of
      new drugs. In the current issue of the Journal, Harrington et al. describe the
      presence and cellular localization of muscarinic receptors in the human colon.
      Morphologically, orientated studies on the cellular expression of GPCRs in the
      human gut have to be encouraged, because these studies will yield data that are
      of therapeutic relevance.

PMID- 20701689
TI  - Non-nutrient causes of low-grade, systemic inflammation: support for a 'canary in
      the mineshaft' view of obesity in chronic disease.
AB  - A form of low-grade, systemic inflammation ('metaflammation') is linked to many
      types of chronic disease. Initially, this was thought to be causally related to
      weight gain and obesity and a possible explanation of the link between obesity
      and disease. However, several lifestyle-related inducers of such inflammation,
      some of which are associated with obesity, but some of which are not, have now
      been identified. The most common of these have been nutritive related, suggesting
      that there could still be a relationship, either directly or indirectly, with
      obesity. Here we provide evidence for non-nutritive inflammatory inducers,
      providing further support for an earlier suggestion that while obesity, beyond a
      point, may have a direct link with disease, this may be neither necessary nor
      sufficient to explain the current epidemic of chronic disease. A more ubiquitous
      cause encompassing all inflammatory inducers is the modern, post-industrial
      environment and lifestyles emanating from this. Obesity may thus be more of 'a
      canary in the mineshaft', warning of bigger global problems, than just a single
      pathway to modern environmentally driven disease.

PMID- 20701690
TI  - Smoke and miRrors: pseudogenes tricking miRNAs.

PMID- 20701691
TI  - Novel potato C2H2-type zinc finger protein gene, StZFP1, which responds to biotic
      and abiotic stress, plays a role in salt tolerance.
AB  - Many TFIIIA-type zinc finger proteins (ZFPs) play important roles in stress
      responses in plants. In the present study, a novel zinc finger protein gene,
      StZFP1, was cloned from potato. StZFP1 is a typical TFIIIA-type two-finger zinc
      finger gene with one B-box domain, one L-box domain and a DLN-box/EAR motif. The
      StZFP1 genes belong to a small gene family with an estimated copy number of four
      or five, located on chromosome I. StZFP1 is constitutively expressed in leaves,
      stems, roots, tubers and flowers of adult plants. Expression of StZFP1 can be
      induced by salt, dehydration and exogenously applied ABA. StZFP1 expression is
      also responsive to infection by the late blight pathogen Phytophthora infestans.
      Transient expression analysis of StZFP1:GFP fusion protein revealed that StZFP1
      is preferentially localised in the nucleus. Ectopic expression of StZFP1, driven
      by the Arabidopsis rd29A promoter in transgenic tobacco, increased plant
      tolerance to salt stress. These results demonstrate that StZFP1 might be involved
      in potato responses to salt and dehydration stresses through an ABA-dependent
      pathway.

PMID- 20701692
TI  - Abscisic acid and late embryogenesis abundant protein profile changes in winter
      wheat under progressive drought stress.
AB  - Three varieties (cv. Pobeda, Katya and Sadovo) of winter wheat (Triticum
      aestivum), differing in their agronomic characteristics, were analysed during
      progressive soil water stress and recovery at early vegetation stages. Changes in
      abscisic acid content, SDS-PAGE and immunoblot profiles of proteins that remained
      soluble upon heating were monitored. Initially higher ABA content in control
      Pobeda and Katya corresponded to earlier expression of the studied late
      embryogenesis abundant (LEA) proteins. A combination of higher ABA content, early
      immunodetection of dehydrins, and a significant increase of WZY2 transcript
      levels were observed in drought-stressed leaves of the tolerant variety Katya.
      One-step RT-PCR analyses of some acidic dehydrin genes (WCOR410b, TADHN)
      documented their relatively constant high expression levels in leaves under
      drought stress during early vegetative development. Neutral WZY2 dehydrin, TaLEA2
      and TaLEA3 transcripts accumulated gradually with increasing water deficit.
      Delayed expression of TaLEA2 and TaLEA3 genes was found in the least drought
      tolerant wheat, Sadovo. The expression profile of WZY2 revealed two distinct and
      separate bands, suggesting alternative splicing, which altered as water stress
      increased.

PMID- 20701693
TI  - Characterisation of Zea mays L. plastidial transglutaminase: interactions with
      thylakoid membrane proteins.
AB  - Chloroplast transglutaminase (chlTGase) activity is considered to play a
      significant role in response to a light stimulus and photo-adaptation of plants,
      but its precise function in the chloroplast is unclear. The characterisation, at
      the proteomic level, of the chlTGase interaction with thylakoid proteins and
      demonstration of its association with photosystem II (PSII) protein complexes was
      accomplished with experiments using maize thylakoid protein extracts. By means of
      a specific antibody designed against the C-terminal sequence of the maize TGase
      gene product, different chlTGase forms were immunodetected in thylakoid membrane
      extracts from three different stages of maize chloroplast differentiation. These
      bands co-localised with those of lhcb 1, 2 and 3 antenna proteins. The most
      significant, a 58 kDa form present in mature chloroplasts, was characterised
      using biochemical and proteomic approaches. Sequential fractionation of thylakoid
      proteins from light-induced mature chloroplasts showed that the 58 kDa form was
      associated with the thylakoid membrane, behaving as a soluble or peripheral
      membrane protein. Two-dimensional gel electrophoresis discriminated, for the
      first time, the 58-kDa band in two different forms, probably corresponding to the
      two different TGase cDNAs previously cloned. Electrophoretic separation of
      thylakoid proteins in native gels, followed by LC-MS mass spectrometry
      identification of protein complexes indicated that maize chlTGase forms part of a
      specific PSII protein complex, which includes LHCII, ATPase and pSbS proteins.
      The results are discussed in relation to the interaction between these proteins
      and the suggested role of the enzyme in thylakoid membrane organisation and
      photoprotection.

PMID- 20701694
TI  - Evidence for an operative glutamine translocator in chloroplasts from maritime
      pine (Pinus pinaster Ait.) cotyledons.
AB  - In higher plants, ammonium is assimilated into amino acids through the glutamine
      synthetase (GS)/glutamate synthase (GOGAT) cycle. This metabolic cycle is
      distributed in different cellular compartments in conifer seedlings: glutamine
      synthesis occurs in the cytosol and glutamate synthesis within the chloroplast. A
      method for preparing intact chloroplasts of pine cotyledons is presented with the
      aim of identifying a glutamine-glutamate translocator. Glutamine-glutamate
      exchange has been studied using the double silicone layer system, suggesting the
      existence of a translocator that imports glutamine into the chloroplast and
      exports glutamate to the cytoplasm. The translocator identified is specific for
      glutamine and glutamate, and the kinetic constants for both substrates indicate
      that it is unsaturated at intracellular concentrations. Thus, the experimental
      evidence obtained supports the model of the GS/GOGAT cycle in developing pine
      seedlings that accounts for the stoichiometric balance of metabolites. As a
      result, the efficient assimilation of free ammonia produced by photorespiration,
      nitrate reduction, storage protein mobilisation, phenylpropanoid pathway or S
      adenosylmethionine synthesis is guaranteed.

PMID- 20701695
TI  - Impact of nitrogen supply on carbon/nitrogen allocation: a case study on amino
      acids and catechins in green tea [Camellia sinensis (L.) O. Kuntze] plants.
AB  - The concentrations of free amino acids (AA) and polyphenols (PP) are important
      determinants of green tea quality. Levels of AA and PP are governed interactively
      by nitrogen (N) supply and carbon (C) status, so the impact of C/N allocation on
      green tea quality was investigated in saplings cultivated hydroponically with
      0.3, 0.75, 1.5 or 4.5 mmol l(-1) N. Activities of glutamine synthetase (GS),
      phenylalanine ammonia lyase (PAL), and phosphoenolpyruvate carboxylase (PEPC)
      were determined, as were concentrations of AA, PP and soluble sugars.
      Concentrations of AA increased with increasing N supply, and the AA profile was
      shifted towards AA characterised by low C/N ratios (arginine, glutamine) and away
      from theanine, the unique non-protein AA that is abundant in Camellia sinensis.
      High N supply significantly reduced the concentrations of PP in young shoots, and
      was accompanied by lower levels of carbohydrates (soluble sugars). Analysis of
      the C and N status and selected enzyme activities, combined with path coefficient
      analysis of variables associated with C and N metabolism, demonstrated increasing
      deviation of C flux to AA under abundant N supply. Accumulation of AA and PP
      depended strongly on N status, and the balance shifted toward increasing
      synthesis of AA associated with enhanced growth, while investment of C in
      secondary metabolites did not change proportionally under the condition of ample
      N supply.

PMID- 20701696
TI  - Reducing the babel in plant volatile communication: using the forest to see the
      trees.
AB  - While plants of a single species emit a diversity of volatile organic compounds
      (VOCs) to attract or repel interacting organisms, these specific messages may be
      lost in the midst of the hundreds of VOCs produced by sympatric plants of
      different species, many of which may have no signal content. Receivers must be
      able to reduce the babel or noise in these VOCs in order to correctly identify
      the message. For chemical ecologists faced with vast amounts of data on volatile
      signatures of plants in different ecological contexts, it is imperative to employ
      accurate methods of classifying messages, so that suitable bioassays may then be
      designed to understand message content. We demonstrate the utility of 'Random
      Forests' (RF), a machine-learning algorithm, for the task of classifying volatile
      signatures and choosing the minimum set of volatiles for accurate discrimination,
      using data from sympatric Ficus species as a case study. We demonstrate the
      advantages of RF over conventional classification methods such as principal
      component analysis (PCA), as well as data-mining algorithms such as support
      vector machines (SVM), diagonal linear discriminant analysis (DLDA) and k-nearest
      neighbour (KNN) analysis. We show why a tree-building method such as RF, which is
      increasingly being used by the bioinformatics, food technology and medical
      community, is particularly advantageous for the study of plant communication
      using volatiles, dealing, as it must, with abundant noise.

PMID- 20701697
TI  - Acclimation of photosynthetic characteristics of the moss Pleurozium schreberi to
      among-habitat and within-canopy light gradients.
AB  - Light availability varies strongly among moss habitats and within the moss
      canopy, and vertical variation in light within the canopy further interacts with
      the age gradient. The interacting controls by habitat and canopy light gradient
      and senescence have not been studied extensively. We measured light profiles,
      chlorophyll (Chl), carotenoid (Car) and nitrogen (N) concentrations, and
      photosynthetic electron transport capacity (J(max)) along habitat and canopy
      light gradients in the widespread, temperate moss Pleurozium schreberi to
      separate sources of variation in moss chemical and physiological traits. We
      hypothesised that this species, like typical feather mosses with both apical and
      lateral growth, exhibits greater plasticity in the canopy than between habitats
      due to deeper within-canopy light gradients. For the among-habitat light
      gradient, Chl, Chl/N and Chl/Car ratio increased with decreasing light
      availability, indicating enhanced light harvesting in lower light and higher
      capacity for photoprotection in higher light. N and J(max) were independent of
      habitat light availability. Within the upper canopy, until 50-60% above-canopy
      light, changes in moss chemistry and photosynthetic characteristics were
      analogous to patterns observed for the between-habitat light gradient. In
      contrast, deeper canopy layers reflected senescence of moss shoots, with pigment
      and nitrogen concentrations and photosynthetic capacity decreasing with light
      availability. Thus, variation in chemical and physiological traits within the
      moss canopy is a balance between acclimation and senescence. This study
      demonstrates extensive light-dependent variation in moss photosynthetic traits,
      but also that between-habitat and within-canopy light gradient affects moss
      physiology and chemistry differently.

PMID- 20701698
TI  - No increase in alpine snowbed productivity in response to experimental
      lengthening of the growing season.
AB  - Climate change effects on snow cover and thermic regime in alpine tundra might
      lead to a longer growing season, but could also increase risks to plants from
      spring frost events. Alpine snowbeds, i.e. alpine tundra from late snowmelt
      sites, might be particularly susceptible to such climatic changes. Snowbed
      communities were grown in large monoliths for two consecutive years, under
      different manipulated snow cover treatments, to test for effects of early (E) and
      late (L) snowmelt on dominant species growth, plant functional traits, leaf area
      index (LAI) and aboveground productivity. Spring snow cover was reduced to assess
      the sensitivity of snowbed alpine species to severe early frost events, and
      dominant species freezing temperatures were measured. Aboveground biomass,
      productivity, LAI and dominant species growth did not increase significantly in E
      compared to L treatments, indicating inability to respond to an extended growing
      season. Edapho-climatic conditions could not account for these results,
      suggesting that developmental constraints are important in controlling snowbed
      plant growth. Impaired productivity was only detected when harsher and more
      frequent frost events were experimentally induced by early snowmelt. These
      conditions exposed plants to spring frosts, reaching temperatures consistent with
      the estimated freezing points of the dominant species ( approximately -10 degrees
      C). We conclude that weak plasticity in phenological response and potential
      detrimental effects of early frosts explain why alpine tundra from snowbeds is
      not expected to benefit from increased growing season length.

PMID- 20701699
TI  - A combined physical and physiological dormancy controls seasonal seedling
      emergence of Geranium robertianum.
AB  - Temperate forest herbs with seeds exhibiting both a physical and a physiological
      dormancy mechanism are rare, and knowledge on the factors regulating germination
      of these species is fragmentary. The biennial Geranium robertianum L. grows
      mainly in temperate woodlands, but can also be found in exposed habitats.
      Seedlings of G. robertianum are known to emerge from spring until autumn, but
      little is known about the environmental factors regulating germination. In this
      study, phenology of seedling emergence and of physical dormancy loss was examined
      for seeds buried at shaded or sunny exposed locations. The role of temperature in
      regulating dormancy and germination was analysed by incubating seeds in
      temperature sequences simulating temperatures that seeds experience in nature.
      The results indicate that most seeds of G. robertianum buried in sunny conditions
      germinate immediately after physical dormancy loss in summer. Seeds buried in
      shaded conditions also lose physical dormancy mainly during summer, but remain
      physiologically dormant and do not germinate until late winter or early spring.
      Besides physical dormancy, seeds of G. robertianum also initially have a high
      level of physiological dormancy, which is reduced during dry storage.
      Physiological dormancy is reduced through chilling in winter, thus enabling the
      seeds to germinate at low temperatures. We conclude that a complex combination of
      physical and physiological dormancy ensures that G. robertianum seeds germinate
      in summer at exposed sites and in early spring at shaded sites.

PMID- 20701700
TI  - Competition intensity at local versus regional spatial scales.
AB  - Studies of competition intensity over natural (i.e. topographic) gradients often
      contradict the results from studies where artificial (i.e. fertilizer) gradients
      have been used. Why should the type of gradient matter? To explore the
      possibilities, we performed experiments to measure competition intensity
      experienced by tree seedlings from grass competitors across a natural resource
      gradient, and simultaneously across artificial soil nutrient (fertiliser)
      gradients. We measured various functional traits (i.e. specific leaf area, leaf
      area, leaf nitrogen content, delta(15)N, delta(13)C, RGR) to gain mechanistic
      insight into the nature of competition across these gradients. Competition
      intensity increased with increasing resource availability, unequivocally at the
      local scale (i.e. with fertilizer application) but not at the regional scale
      (i.e. across the natural productivity gradient). Our measurements of plant traits
      were generally consistent with measurements of competition intensity, and
      demonstrate that competition occurs even when resource levels are low.
      Competition mainly acted to reduce the growth of Eucalyptus seedlings. Functional
      (physiological) traits in the Eucalyptus seedlings were not strongly affected by
      competitors, with the possible exception of delta(15)N, which may effectively
      integrate information on soil nutrient, moisture and leaf processes.

PMID- 20701701
TI  - Assessing facilitative responses to a nurse shrub at the community level: the
      example of Potentilla fruticosa in a sub-alpine grassland of northwest China.
AB  - Biotic interaction studies have revealed a large discrepancy among experiments in
      target responses to the effects of neighbours, which may in part be due to both
      high species-specificity of plant responses and low number of target species used
      in experiments. Our aim was to assess facilitative responses at the community
      level and the role of both functional groups and ecological attributes of target
      species. In a sub-alpine grassland on the eastern Tibet plateau, we assessed
      growth responses of all species in the community to removal of a dominant shrub.
      We also measured changes in the main environmental variables. Species responses
      were analysed by functional group and in relation to their mean regional
      altitudinal distribution. All significant interactions were positive and affected
      one-third of the total species richness of the community. All functional groups
      were facilitated but forbs were less strongly facilitated than in the two other
      groups. High-alpine species were less strongly facilitated than low-sub-alpine
      species, but the strength of this relationship was weaker than that reported in
      previous work. There was evidence of a decrease in extreme temperatures below the
      canopy of the shrub but no variations in soil moisture. We conclude that the
      highly stressful conditions induced by the dry continental climate of the eastern
      Tibet plateau are a main driver of the exclusive dominance of positive
      interactions. Assessing interactive responses at the community level is likely to
      provide a useful tool to better understand the role of biotic interactions in
      community responses to environmental changes.

PMID- 20701702
TI  - A survey of the mycorrhization of Southeast Asian ferns and lycophytes.
AB  - The colonisation of land by plants may not have been possible without
      mycorrhizae, which supply the majority of land plants with nutrients, water and
      other benefits. In this sense, the mycorrhization of basal groups of land plants
      such as ferns and lycophytes is of particular interest, yet only about 9% of fern
      and lycophyte species have been sampled for their mycorrhization status, and no
      community-level analyses exist for tropical fern communities. In the present
      study, we screened 170 specimens of ferns and lycophytes from Malaysia and
      Sulawesi (Indonesia), representing 126 species, and report the mycorrhization
      status for 109 species and 19 genera for the first time. Mycorrhizal
      colonisations were detected in 96 (56.5%) of the specimens, 85 of which
      corresponded to arbuscular mycorrhizae (AMF), three to dark-septate endophytes
      (DSE) and four to mixed colonisations (AMF + DSE). DSE colonisations were lower
      than in comparable samples of ferns from the Andes, suggesting a geographical or
      taxonomic pattern in this type of colonisation. Epiphytes had significantly lower
      levels of colonisation (26.1%) than terrestrial plants (70.7%), probably due to
      the difficulty of establishment of mycorrhizal fungi in the canopy habitat.

PMID- 20701703
TI  - Developmental anatomy of seedlings of Indodalzellia gracilis (Podostemaceae).
AB  - In Tristichoideae, aquatic angiosperms in the family Podostemaceae, Terniopsis,
      Tristicha, Indotristicha and Cussetia have creeping roots with flanking
      (sub)cylindrical shoots, while Dalzellia is rootless and has crustose shoots.
      Indodalzellia gracilis, sister to a clade of Dalzellia zeylanica and
      Indotristicha ramosissima, has subcrustose shoots on the side of creeping roots,
      suggesting that I. gracilis may be a key species to reveal how saltational
      evolution of the body plan occurred in these three species. We investigated
      developmental morphology of I. gracilis seedlings grown in culture, using
      scanning electron microscopy and semi-thin serial sections. As in D. zeylanica,
      the plumular apical meristem in the seedling gives rise to two shoot apical
      meristems, which develop into horizontal subcrustose shoots with dorsal and
      marginal leaves. Neither radicle nor adventitious root is produced from the
      hypocotyl, but an adventitious root arises endogenously from the juvenile shoot
      and from some shoots of adult plants. These results, together with the
      phylogenetic relationships, suggest that the Indodalzellia seedling evolved by
      loss of the adventitious root derived from the hypocotyl, appearance of shoots in
      the axil of cotyledons, and appearance of adventitious roots from adventitious
      shoots. The difference in place of origin of the root between Indodalzellia and
      I. ramosissima suggests differing evolutionary origin of the root in
      Tristichoideae.

PMID- 20701704
TI  - Two neutral variants segregating at the gametophytic self-incompatibility locus
      of European pear (Pyrus communis L.) (Rosaceae, Pyrinae).
AB  - Extensive survey of the S-locus diversity of plant species with RNase-based
      gametophytic self-incompatibility has failed to identify neutral variation
      segregating within S-allele specificities. Although this is the expected result
      according to population genetics theory, it conflicts with recent models of S
      allele evolution, which suggest that new specificities might arise by a
      continuous process of subtle changes that individually do not alter the
      specificity of the S-genes, but whose cumulative effects result in new S-allele
      functions. Genomic analysis of S-RNase sequences associated with the S(104)
      (=S(4), =S(b)) allele of European pear (Pyrus communis L.) cultivars yielded two
      distinct variants (named herein S(104-1) and S(104-2)) that differed at five
      nucleotide positions within the open reading frame, two of which resulted in
      changes in the predicted protein sequence. Test-cross experiments indicated that
      the S-alleles associated with the S(104-1) and S(104-2)RNases exhibit the same
      pollen and pistil functions, suggesting that they are two neutral variants
      segregating within the S(104) haplotype of European pear. These allelic forms
      might represent transitional states in the process of generating new
      specificities in the species, in accordance with models that predict S-function
      transition through neutral intermediates. This possibility was further evaluated
      through the pattern of molecular evolution of functionally distinct European pear
      S-RNases, which indicated that most recent S-allele diversification in this
      species proceeded in the absence of adaptive selective pressure.

PMID- 20701705
TI  - Genetic diversity in inter-simple sequence repeat profiles across natural
      populations of Indian pomegranate (Punica granatum L.).
AB  - Pomegranate (Punica granatum L.), in the monogeneric family Punicaceae, is found
      in Iran, Afghanistan, India and Mediterranean countries. Iran is considered to be
      its primary centre of origin. In India, pomegranate occurs naturally only in the
      Western Himalayan regions of Jammu and Kashmir, Himachal Pradesh and Uttarakhand
      States. However, there is no information about genetic variation in wild
      pomegranate at population level. In this paper, we describe genetic diversity
      across natural populations of Indian pomegranate based on inter-simple sequence
      repeat (ISSR) markers. Forty-nine accessions representing eight populations from
      two regions were analysed using ISSR. Seventeen ISSR primers resulted in 268
      polymorphic bands, with 87.01% polymorphism throughout the accessions. Pair-wise
      population genetic distances ranged from 0.05 to 0.45, with a mean of 0.25
      between populations. amova and Nei's genetic diversity analyses revealed higher
      genetic variation within populations than among populations. A higher genetic
      differentiation (G(ST)) was observed between the spatially distant populations,
      indicating a low level of genetic exchange (Nm) among these populations. However,
      clustering of populations was not in accordance with their geographical
      affiliations in the tree. The results indicate that the ISSR method is
      sufficiently informative and powerful to assess genetic variability in
      pomegranate, and that patterns of genetic variability observed among populations
      of wild pomegranate from the Western Himalaya differ. Estimation of genetic
      variation reported here provides a significant insight for in situ conservation
      and exploitation of genetic resources for this economically important species as
      potential breeding material.

PMID- 20701706
TI  - Reduced recombination in gynodioecious populations of a facultative apomictic
      orchid.
AB  - Many plants combine sexual reproduction with some form of asexual reproduction to
      different degrees, and lower genetic diversity is expected with asexuality.
      Moreover, the ratios of sexual morphs in species with gender dimorphism are
      expected to vary in proportion to the reproductive success of the sexual process.
      Hence, sex ratios can directly influence the genetic structure and diversity of a
      population. We investigated genotypic diversity in 23 populations of a
      facultative, apomictic gynodioecious orchid, Satyrium ciliatum, to examine the
      effect on genotypic diversity of variation in the frequency of females and in the
      amount of sexual reproduction. The study involved one pure female, seven
      gynodioecious (both females and hermaphrodites present) and 15 hermaphroditic
      populations. Pollinia receipt was higher in hermaphroditic than in gynodioecious
      populations. Analyses of variation in ISSRs demonstrated that genotypic diversity
      was high in all populations and was not significantly different between
      hermaphroditic and gynodioecious populations. We used character compatibility
      analysis to determine the extent to which recombination by sexual reproduction
      contributed to genotypic diversity. The results indicate that the contribution of
      recombination to genotypic diversity is higher in hermaphroditic than in
      gynodioecious populations, consistent with the finding that hermaphroditic
      populations received higher amounts of pollinia. Our finding of reduced
      recombination in gynodioecious populations suggests that maintenance of sex in
      hermaphrodites plays an important role in generating genotypic diversity in this
      apomictic orchid.

PMID- 20701707
TI  - Genome size dynamics in Artemisia L. (Asteraceae): following the track of
      polyploidy.
AB  - Polyploidy is a key factor in the evolution of higher plants and plays an
      important role in the variation of plant genomes, leading to speciation in some
      cases. During polyploidisation, different balancing processes take place at the
      genomic level that can promote variation in nuclear DNA content. We estimated
      genome size using flow cytometry in 84 populations of 67 Artemisia species and
      one population of Crossostephium chinense. A total of 73 sequences of nrDNA ITS
      and 3'-ETS were newly generated and analysed, together with previously published
      sequences, to address the evolution of genome size in a phylogenetic framework.
      Differences in 2C values were detected among some lineages, as well as an
      increase of genome size heterogeneity in subgenera whose phylogenetic
      relationships are still unclear. We confirmed that the increase in 2C values in
      Artemisia polyploids was not proportional to ploidy level, but 1Cx genome size
      tended to decrease significantly when high ploidy levels were reached. The
      results lead us to hypothesise that genome size in polyploids tends to a maximum
      as it follows saturation behaviour, in agreement with the Michaelis-Menten model.
      We tested different arithmetic functions with our dataset that corroborated a non
      linear relationship of genome size increase in polyploids, allowing us to suggest
      a theoretical upper limit for the DNA content of this genus.

PMID- 20701708
TI  - The effect of musical experience on emotional self-reports and
      psychophysiological responses to dissonance.
AB  - To study the influence of musical education on emotional reactions to dissonance,
      we examined self-reports and physiological responses to dissonant and consonant
      musical excerpts in listeners with low (LE: n=15) and high (HE: n=13) musical
      experience. The results show that dissonance induces more unpleasant feelings and
      stronger physiological responses in HE than in LE participants, suggesting that
      musical education reinforces aversion to dissonance. Skin conductance (SCR) and
      electromyographic (EMG) signals were analyzed according to a defense cascade
      model, which takes into account two successive time windows corresponding to
      orienting and defense responses. These analyses suggest that musical experience
      can influence the defense response to dissonance and demonstrate a powerful role
      of musical experience not only in autonomic but also in expressive responses to
      music.

PMID- 20701710
TI  - Interstimulus intervals for skin conductance response measurement.
AB  - This study examined, using the Concealed Information paradigm, whether
      interstimulus intervals (ISI) typically used for electrodermal measurement can be
      shortened. An ISI ranging from 16 s to 24 s (with a mean of 20 s) was compared
      with an ISI shortened by 50% using a within-participants design. It was
      demonstrated that this shortening had no effect on the differential skin
      conductance responses to the personally significant details and nearly identical
      detection efficiency was observed under the 2 ISIs. However, overall responses
      were attenuated with the shorter ISI. The implications of these results for
      various types of studies, using skin conductance responses, were discussed.

PMID- 20701709
TI  - FN400 potentials are functionally identical to N400 potentials and reflect
      semantic processing during recognition testing.
AB  - The "F" in FN400 denotes a more frontal scalp distribution relative to the
      morphologically similar N400 component-a distinction consistent with the
      hypothesized distinct roles of FN400 in familiarity memory versus N400 in
      language. However, no direct comparisons have substantiated these assumed
      dissimilarities. To this end, we manipulated short-term semantic priming during a
      recognition test. Semantic priming effects on N400 were indistinguishable from
      memory effects at the same latency, and semantic priming strongly modulated the
      "FN400," despite having no influence on familiarity memory. Thus, no evidence
      suggested either electrophysiological or functional differences between the N400
      and FN400, and findings were contrary to the linking of the "FN400" to
      familiarity. Instead, it appears that semantic/conceptual priming (reflected in
      the N400) occurs during recognition tests and is frequently (mis)labeled as FN400
      and attributed to familiarity.

PMID- 20701711
TI  - Repetitive exposure: brain and reflex measures of emotion and attention.
AB  - Effects of massed repetition on the modulation of the late positive potential
      elicited during affective picture viewing were investigated in two experiments.
      Despite a difference in the number of repetitions across studies (from 5 to 30),
      results were quite similar: The late positive potential continued to be enhanced
      when participants viewed emotional, compared to neutral, pictures. On the other
      hand, massed repetition did prompt a reduction in the late positive potential
      that was most pronounced for emotional pictures. Startle probe P3 amplitude
      generally increased with repetition, suggesting diminished attention allocation
      to repeated pictures. The blink reflex, however, continued to be modulated by
      hedonic valence, despite massive massed repetition. Taken together, the data
      suggest that the amplitude of the late positive potential during picture viewing
      reflects both motivational significance and attention allocation.

PMID- 20701712
TI  - Comprehending how visual context influences incremental sentence processing:
      Insights from ERPs and picture-sentence verification.
AB  - To re-establish picture-sentence verification-discredited possibly for its over
      reliance on post-sentence response time (RT) measures-as a task for situated
      comprehension, we collected event-related brain potentials (ERPs) as participants
      read a subject-verb-object sentence, and RTs indicating whether or not the verb
      matched a previously depicted action. For mismatches (vs. matches), speeded RTs
      were longer, verb N400s over centro-parietal scalp larger, and ERPs to the object
      noun more negative. RTs (congruence effect) correlated inversely with the centro
      parietal verb N400s, and positively with the object ERP congruence effects. Verb
      N400s, object ERPs, and verbal working memory scores predicted more variance in
      RT effects (50%) than N400s alone. Thus, (1) verification processing is not all
      post-sentence; (2) simple priming cannot account for these results; and (3)
      verification tasks can inform studies of situated comprehension.

PMID- 20701713
TI  - An electrophysiological measure of visual short-term memory capacity within and
      across hemifields.
AB  - Recent electrophysiological research has identified a specific contralateral
      correlate of the contents of visual short-term memory (VSTM). This posterior
      contralateral delay activity (CDA) persists during the retention period, and its
      amplitude is modulated by the number of items held at any one time. Here we show
      that, despite the contralateral nature of this activity, its amplitude is
      modulated by the number of objects from both hemifields. When objects from one
      side of the visual field are held in memory, CDA activity increased for arrays of
      one, two, and three objects, but stopped getting larger for arrays of four
      objects. However, when objects from both sides are memorized at the same time,
      CDA activity reached its asymptotic limit for arrays of two objects per side.
      These results suggest that, in spite of being contralaterally organized, VSTM is
      limited by the number of objects from both hemifields.

PMID- 20701714
TI  - Dietary concerns in patients with advanced chronic kidney disease introduction.

PMID- 20701715
TI  - Dietary protein intake in patients with advanced chronic kidney disease and on
      dialysis.
AB  - Many patients with chronic kidney disease (CKD), particularly those with stage 5
      CKD, have protein wasting. The degree to which increased morbidity and mortality
      seen in these patients is due to protein depletion rather than to the often
      accompanying comorbidity is not clear. High protein diets lead to the
      accumulation of metabolites of protein that are potentially toxic. The MDRD
      Study, which investigated the effects of three levels of dietary protein and
      phosphorus intakes and two blood pressure goals on the progression of CKD, has
      several limitations. Several meta-analyses have examined the effects of low
      protein diets (LPD) on the progression of CKD. It is possible that the lower SUN
      levels or lesser degree of uremic symptoms may have contributed to the positive
      findings of LPD in the meta-analyses of Fouque and Pedrini et al., when compared
      with the study of Kasiske et al. A number of published reports indicate that LPD
      provide adequate protein for almost all clinically stable CKD patients and do not
      adversely affect body composition. In general, there are no large differences in
      the protein intake recommended by different expert groups for a given stage of
      CKD.

PMID- 20701716
TI  - Energy balance in advanced chronic kidney disease and end-stage renal disease.
AB  - Energy intake, resting energy expenditure, and energy expended for physical
      activity (EEPA) are components of energy balance that may be disrupted by a
      number of disorders and clinical conditions commonly present in advanced chronic
      kidney disease (CKD) and end-stage renal disease (ESRD). Energy intake of
      patients with CKD has been consistently lower than the recommended intake in
      multiple reports. On the other hand, while reduced energy intake due to anorexia
      may be applicable for ESRD patients with overt protein-energy wasting, it is
      potentially unrealistic for overweight or obese subjects who are able to maintain
      their body weight. Studies on resting energy expenditure have provided mixed
      results, most likely as a consequence of differences in the population
      characteristics, clinical conditions, and stage of the disease. Finally, although
      there is lack of specific studies on EEPA, there is evidence that ESRD patients,
      particularly those undergoing hemodialysis are in general less active than
      sedentary healthy individuals. These observations may raise questions regarding
      the accuracy of dietary reports and the uncertainties related to the energy
      requirements, optimal dietary energy intake, and recommendations for physical
      activity in these patients.